PMID- 27686192
TI  - [Not Available].

PMID- 27686193
TI  - [Not Available].

PMID- 27686195
TI  - [Not Available].

PMID- 27686194
TI  - [Not Available].

PMID- 27686196
TI  - [Not Available].

PMID- 27686197
TI  - [Not Available].

PMID- 27686198
TI  - [Not Available].

PMID- 27686199
TI  - [Not Available].

PMID- 27686200
TI  - The relationship between meat and evolution.

PMID- 27686201
TI  - [Can Health-Norway be united into one kingdom?].

PMID- 27686202
TI  - [Not Available].

PMID- 27686203
TI  - [Research misconduct: Knowledge, actions and attitudes of PhD candidates].
AB  - BACKGROUND Increasing attention is being paid to research misconduct in academic
      journals and in the media, but we know relatively little about its extent or
      attitudes to research misconduct, or how these are changing. This study therefore
      aims to investigate PhD candidates' knowledge, own actions and attitudes to
      specific forms of research misconduct.MATERIAL AND METHOD In autumn 2015, an
      anonymous questionnaire survey was distributed to all participants in the
      introductory course for PhD candidates at the Faculty of Medicine at the
      University of Oslo.RESULTS Altogether 77 PhD candidates (79 %) responded to the
      questionnaire. A total of 62 % conducted clinical research and 25 % conducted
      basic research. Around one in four had heard about serious forms of research
      misconduct in the previous year, and around 4 % were aware of various forms of
      serious research misconduct in their own department in the previous year.
      Compared to earlier studies, an increasing number (16 %) responded that they had
      been subjected to unethical pressure with regard to inclusion or order of
      authors. Approximately two-thirds were uncertain of whether their department had
      written policies for academic conduct. One-third of PhD candidates did not
      disassociate themselves from actions that are generally viewed as scientific
      misconduct. One-tenth thought it acceptable to falsify or fabricate data in order
      to expedite publication, one-fifth did not object to taking the credit for
      others' ideas, and almost half did not believe it was wrong to attempt a number
      of methods of analysis until one arrived at a significant answer.INTERPRETATION
      PhD candidates at the Faculty of Medicine were aware of research misconduct, both
      generally and from their own department. They themselves reported some type of
      scientific misconduct, and a large majority were uncertain of their department's
      guidelines. Some of the candidates also accepted several forms of research
      misconduct. 

PMID- 27686204
TI  - [Attendance in the Norwegian Breast Cancer Screening Programme].
AB  - BACKGROUND: A high rate of attendance among women invited to the Norwegian Breast
      Cancer Screening Programme (NBCSP) is essential to achieve optimal effect,
      including reduction in breast cancer mortality. This article describes attendance
      in the programme by county, period and women's age at invitation. MATERIAL AND
      METHOD: All women in the age group 50 - 69 years who are registered in the
      National Population Register are invited to attend the NBCSP every second year.
      In the study period 2007 - 2014, 2 142 369 invitations were sent, and 1 600 293
      screening examinations were performed for 710 169 women. Use of the data is
      pursuant to the Cancer Registry Regulations. RESULTS: Altogether 84 % of the
      women invited attended at least once in the study period. The average attendance
      rate per screening round was 75 %. In Rogaland, Nordland and Sogn og Fjordane
      counties more than 80 % attended, while in Oslo the figure was 62 %. The highest
      rate of attendance recorded was for women in the age group 62 - 67 years. The
      attendance in the prior screening round was of influence for reattendance.
      INTERPRETATION: The mammography screening programme has a high level of
      acceptance among women in the target group. Possible reasons for the variation in
      attendance among the county districts should be identified.

PMID- 27686205
TI  - Congenital thrombotic thrombocytopenic purpura.
AB  - BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) is a rare,
      hereditary disorder. Clinically it presents as episodic microangiopathic
      haemolytic anaemia and thrombocytopenia with varying degrees of damage to
      internal organs. The condition may present in neonates, but can also present for
      the first time in adulthood. The prevalence of congenital TTP is particularly
      high in Norway, and it is therefore important for Norwegian doctors to be aware
      of the condition. In this article we review the main characteristics of the
      disease, including its diagnosis and management, and introduce potential new
      treatments for the future. METHOD: The article is based on a literature search in
      PubMed as well as the authors' own research and clinical experience. RESULTS:
      There was great variation in the severity of congenital TTP: from neonatal
      mortality to disease-free intervals of several years. Episodes are generally
      precipitated by a trigger. Acute episodes are treated with plasma infusions, and
      approximately half of all patients experience frequent episodes and require
      prophylactic infusions to avoid organ damage. The risk of episodes is greatest in
      neonates, during pregnancy and in association with infections. INTERPRETATION:
      There is little research-based evidence regarding long-term prognosis in
      congenital TTP. There is also a need for guidelines to help identify candidates
      for prophylactic treatment. An international patient registry would provide
      useful information and form the basis for better guidelines on the monitoring and
      treatment of these patients.

PMID- 27686206
TI  - [A 4-year-old girl with diarrhoea, paresis and mutism].
AB  - BACKGROUND Rotavirus is a common cause of gastroenteritis in children.
      Neurological manifestations associated with rotavirus infections are well
      described and range from benign afebrile convulsions to lethal encephalopathy or
      encephalitis.CASE PRESENTATION We present an uncommon neurological manifestation
      in a Caucasian child in the course of a rotavirus infection. A 4-year old girl
      presented with mutism, hypotonia and reduced consciousness. Magnetic resonance
      imaging revealed diffusion abnormalities in the splenium corpus callosum and
      bilaterally in the nuclei dentate in the cerebellum. She was diagnosed with
      rotavirus cerebellitis.INTERPRETATION Her clinical symptoms and the magnetic
      resonance imaging abnormalities were uncommon and previously described in only a
      few Caucasian children. The outcome has varied, and some children have shown long
      term neurological sequela. Treatment with immunoglobulins and corticosteroids has
      been used in similar cases, but there is no established treatment for this
      condition. 

PMID- 27686207
TI  - [Norwegian forensic medicine at kitchen tables and park benches].

PMID- 27686208
TI  - [Child cancer is different].

PMID- 27686209
TI  - [Forced alkaline diuresis - really?].

PMID- 27686210
TI  - [Not Available].

PMID- 27686211
TI  - [Not Available].

PMID- 27686212
TI  - [Not Available].

PMID- 27686213
TI  - [Not Available].

PMID- 27686214
TI  - [Not Available].

PMID- 27686215
TI  - High expression of MAP7 predicts adverse prognosis in young patients with
      cytogenetically normal acute myeloid leukemia.
AB  - Microtubule-associated protein 7 (MAP7) plays an important role in cancer cells.
      In this study, we identified the prognostic significance of MAP7 expression in
      cytogenetically normal acute myeloid leukemia (CN-AML) patients (aged <60 years)
      based on several microarray datasets. In the first group (n = 129), high MAP7
      expression (MAP7high) was associated with adverse overall survival (OS; P =
      0.0441) and event-free survival (EFS; P = 0.0114) compared with low MAP7
      expression (MAP7low). In addition, the prognostic significance of MAP7 was
      confirmed by European Leukemia Net (ELN) intermediate-I genetic categories and
      multivariable analysis. In the second independent group of CN-AML patients (aged
      <60 years), MAP7high was also associated with adverse OS (n = 88, OS; P =
      0.00811). To understand the inherent mechanisms of MAP7's prognosis, we
      investigated genome-wide gene/microRNA expression signatures associated with MAP7
      expression. Several known oncogenic genes/microRNAs and anti-oncogenic
      genes/microRNAs were disordered in MAP7high CN-AML patients. In conclusion,
      MAP7high is an adverse prognostic biomarker for CN-AML, which may be attributed
      to the distinctive genome-wide gene/microRNA expression and related cell
      signaling pathways.

PMID- 27686216
TI  - Development of dopant-free conductive bioelastomers.
AB  - Conductive biodegradable materials are of great interest for various biomedical
      applications, such as tissue repair and bioelectronics. They generally consist of
      multiple components, including biodegradable polymer/non-degradable conductive
      polymer/dopant, biodegradable conductive polymer/dopant or biodegradable
      polymer/non-degradable inorganic additives. The dopants or additives induce
      material instability that can be complex and possibly toxic. Material softness
      and elasticity are also highly expected for soft tissue repair and soft
      electronics. To address these concerns, we designed a unicomponent dopant-free
      conductive polyurethane elastomer (DCPU) by chemically linking biodegradable
      segments, conductive segments, and dopant molecules into one polymer chain. The
      DCPU films which had robust mechanical properties with high elasticity and
      conductivity can be degraded enzymatically and by hydrolysis. It exhibited great
      electrical stability in physiological environment with charge. Mouse 3T3
      fibroblasts survived and proliferated on these films exhibiting good
      cytocompatibility. Polymer degradation products were non-toxic. DCPU could also
      be processed into a porous scaffold and in an in vivo subcutaneous implantation
      model, exhibited good tissue compatibility with extensive cell infiltration over
      2 weeks. Such biodegradable DCPU with good flexibility and elasticity,
      processability, and electrical stability may find broad applications for tissue
      repair and soft/stretchable/wearable bioelectronics.

PMID- 27686217
TI  - Characterization of Amyloid Cores in Prion Domains.
AB  - Amyloids consist of repetitions of a specific polypeptide chain in a regular
      cross-beta-sheet conformation. Amyloid propensity is largely determined by the
      protein sequence, the aggregation process being nucleated by specific and short
      segments. Prions are special amyloids that become self-perpetuating after
      aggregation. Prions are responsible for neuropathology in mammals, but they can
      also be functional, as in yeast prions. The conversion of these last proteins to
      the prion state is driven by prion forming domains (PFDs), which are generally
      large, intrinsically disordered, enriched in glutamines/asparagines and depleted
      in hydrophobic residues. The self-assembly of PFDs has been thought to rely
      mostly on their particular amino acid composition, rather than on their sequence.
      Instead, we have recently proposed that specific amyloid-prone sequences within
      PFDs might be key to their prion behaviour. Here, we demonstrate experimentally
      the existence of these amyloid stretches inside the PFDs of the canonical Sup35,
      Swi1, Mot3 and Ure2 prions. These sequences self-assemble efficiently into highly
      ordered amyloid fibrils, that are functionally competent, being able to promote
      the PFD amyloid conversion in vitro and in vivo. Computational analyses indicate
      that these kind of amyloid stretches may act as typical nucleating signals in a
      number of different prion domains.

PMID- 27686218
TI  - Comparison of diagnostic validity of mannitol and methacholine challenges and
      relationship to clinical status and airway inflammation in steroid-naive
      asthmatic patients.
AB  - OBJECTIVES: The purpose of this study was to demonstrate and compare the
      diagnostic validity of two bronchial challenges and to investigate their
      correlation with patient clinical status, atopy and inflammation markers.
      METHODS: Eighty-eight patients, 47 women and 41 men, mean age 38.56 +/- 16.73
      years who presented with asthma related symptoms and were not on any anti-asthma
      medication, were challenged with mannitol and methacholine on separate days.
      Medical history regarding asthmatic symptoms, physical examination, skin prick
      tests and FeNO levels were also assessed. The clinical diagnosis of asthma was
      based on bronchodilator reversibility test. RESULTS: Sixty-seven patients were
      diagnosed with asthma and 21 without asthma. Both methacholine (P < 0.014) and
      mannitol (P < 0.000) challenges were significant in diagnosing asthma. The
      positive/negative predictive value was 93.33%/41.86% for methacholine,
      97.72%/45.45% for mannitol and 97.05%/45.45%. for both methods assessed together.
      Worthy of note that 22% of asthmatics had both tests negative. There was a
      negative correlation between PC20 of methacholine and the FeNO level P < 0.001,
      and positive with the PD15 of mannitol P < 0.001 and the pre-test FEV1% pred P <
      0.005, whereas PD15 of mannitol was negatively correlated with the FeNO level P <
      0.001. Furthermore, dyspnea was the only asthmatic symptom associated with FeNO
      level P < 0.035 and the positivity of mannitol P < 0.014 and methacholine P <
      0.04. CONCLUSIONS: Both challenge tests were equivalent in diagnosing asthma.
      Nevertheless, specificity appeared to be slightly higher in mannitol challenge.

PMID- 27686219
TI  - Process-based design of dynamical biological systems.
AB  - The computational design of dynamical systems is an important emerging task in
      synthetic biology. Given desired properties of the behaviour of a dynamical
      system, the task of design is to build an in-silico model of a system whose
      simulated be- haviour meets these properties. We introduce a new, process-based,
      design methodology for addressing this task. The new methodology combines a
      flexible process-based formalism for specifying the space of candidate designs
      with multi-objective optimization approaches for selecting the most appropriate
      among these candidates. We demonstrate that the methodology is general enough to
      both formulate and solve tasks of designing deterministic and stochastic systems,
      successfully reproducing plausible designs reported in previous studies and
      proposing new designs that meet the design criteria, but have not been previously
      considered.

PMID- 27686220
TI  - Erratum: Shear-mediated contributions to the effective properties of soft
      acoustic metamaterials including negative index.

PMID- 27686221
TI  - A Novel Reference Security Model with the Situation Based Access Policy for
      Accessing EPHR Data.
AB  - Electronic Patient Health Record (EPHR) systems may facilitate a patient not only
      to share his/her health records securely with healthcare professional but also to
      control his/her health privacy, in a convenient and easy way even in case of
      emergency. In order to fulfill these requirements, it is greatly desirable to
      have the access control mechanism which can efficiently handle every circumstance
      without negotiating security. However, the existing access control mechanisms
      used in healthcare to regulate and restrict the disclosure of patient data are
      often bypassed in case of emergencies. In this article, we propose a way to
      securely share EPHR data under any situation including break-the-glass (BtG)
      without compromising its security. In this regard, we design a reference security
      model, which consists of a multi-level data flow hierarchy, and an efficient
      access control framework based on the conventional Role-Based Access Control
      (RBAC) and Mandatory Access Control (MAC) policies.

PMID- 27686222
TI  - Processing Time Reduction: an Application in Living Human High-Resolution
      Diffusion Magnetic Resonance Imaging Data.
AB  - High Angular Resolution Diffusion Imaging (HARDI) is a type of brain imaging that
      collects a very large amount of data, and if many subjects are considered then it
      amounts to a big data framework (e.g., the human connectome project has 20
      Terabytes of data). HARDI is also becoming increasingly relevant for clinical
      settings (e.g., detecting early cerebral ischemic changes in acute stroke, and in
      pre-clinical assessment of white matter-WM anatomy using tractography). Thus,
      this method is becoming a routine assessment in clinical settings. In such
      settings, the computation time is critical, and finding forms of reducing the
      processing time in high computation processes such as Diffusion Spectrum Imaging
      (DSI), a form of HARDI data, is very relevant to increase data-processing speed.
      Here we analyze a method for reducing the computation time of the dMRI-based
      axonal orientation distribution function h by using Monte Carlo sampling-based
      methods for voxel selection. Results evidenced a robust reduction in required
      data sampling of about 50 % without losing signal's quality. Moreover, we show
      that the convergence to the correct value in this type of Monte Carlo HARDI/DSI
      data-processing has a linear improvement in data-processing speed of the ODF
      determination. Although further improvements are needed, our results represent a
      promissory step for future processing time reduction in big data.

PMID- 27686224
TI  - Profiling risk for acute rejection in kidney transplantation: recipient age is a
      robust risk factor.
AB  - Careful management of immunosuppression is paramount to prevent acute rejection
      in kidney transplantation. We studied a cohort of 139,875 kidney transplant
      recipients from the Organ Procurement and Transplantation Network (OPTN) database
      between 2002 and 2013. We confirmed the analysis with a cohort of 35,277 who
      received thymoglobulin induction with tacrolimus maintenance, and a third cohort
      of 12,161 recipients who received basiliximab induction with tacrolimus
      maintenance. We performed multivariate logistic regression analyses on data from
      all three cohorts and identified independent risk factors for treated acute
      rejection at 1 year. Recipient age was a robust risk factor for rejection in all
      three cohorts in a dose response pattern. Young age (18-25 years) was among the
      strongest risk factors for rejection in all three cohorts; thymoglobulin cohort:
      OR 1.87 (1.59-2.19); basiliximab cohort: OR 2.41 (1.89-3.05); and inclusive
      cohort: OR 1.97 (1.83-2.12). The opposite was true for old age (65-69 years);
      thymoglobulin cohort: OR 0.69 (0.59-0.81); basiliximab cohort: OR 0.77 (0.62
      0.96); and inclusive cohort: OR 0.75 (0.70-0.80). This study is unique because it
      is the largest and most comprehensive multivariate analysis that demonstrates
      recipient age is a robust risk factor for acute rejection in an inverse dose
      response pattern.

PMID- 27686223
TI  - Body fluid levels of neuroactive amino acids in autism spectrum disorders: a
      review of the literature.
AB  - A review of studies on the body fluid levels of neuroactive amino acids,
      including glutamate, glutamine, taurine, gamma-aminobutyric acid (GABA), glycine,
      tryptophan, D-serine, and others, in autism spectrum disorders (ASD) is given.
      The results reported in the literature are generally inconclusive and
      contradictory, but there has been considerable variation among the previous
      studies in terms of factors such as age, gender, number of subjects, intelligence
      quotient, and psychoactive medication being taken. Future studies should include
      simultaneous analyses of a large number of amino acids [including D-serine and
      branched-chain amino acids (BCAAs)] and standardization of the factors mentioned
      above. It may also be appropriate to use saliva sampling to detect amino acids in
      ASD patients in the future-this is noninvasive testing that can be done easily
      more frequently than other sampling, thus providing more dynamic monitoring.

PMID- 27686226
TI  - Comparison of mirabegron and imidafenacin for efficacy and safety in Japanese
      female patients with overactive bladder: A randomized controlled trial (COMFORT
      study).
AB  - OBJECTIVES: To evaluate the efficacy and safety of mirabegron compared with
      imidafenacin for the treatment of female patients with overactive bladder.
      METHODS: Patients (n = 89) were randomized to receive 0.1 mg imidafenacin twice
      daily (n = 47) or 50 mg mirabegron once daily (n = 42) for 12 weeks. The primary
      efficacy end-point was change in total Overactive Bladder Symptom Score.
      Secondary efficacy end-points included change in Overactive Bladder Symptom
      Score, 3-day micturition diary, International Prostate Symptom Score and
      Overactive Bladder Questionnaire. Safety assessments included adverse events,
      vital signs, post-void residual volume and patient-reported incidence, and
      severity of distinctive symptoms related to adverse events. RESULTS: The
      mirabegron group showed a significantly reduced mean total Overactive Bladder
      Symptom Score from baseline, but no significant differences were noted in change
      of total Overactive Bladder Symptom Score compared with the imidafenacin group.
      Significant improvements in secondary efficacy end-points were observed regarding
      the mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean
      number of incontinence episodes/24 h, mean volume voided/micturition, total
      International Prostate Symptom Score and quality of life in both groups, with no
      significant differences between the groups. The overall incidence of adverse
      events and the incidence of dry mouth were significantly higher in the
      imidafenacin group than in the mirabegron group. Patient-reported incidence and
      the severity of dry mouth were significantly exacerbated in the imidafenacin
      group. CONCLUSIONS: Treatment with 50 mg mirabegron once daily effectively
      relieves overactive bladder symptoms in women with fewer adverse events than
      treatment with antimuscarinics.

PMID- 27686225
TI  - Association of Calf Muscle Pump Stimulation With Sleep Quality in Adults.
AB  - Prevention of lower extremity fluid pooling (LEFP) is associated with improved
      sleep quality. Physical activity and compression stockings are non-invasive
      methods used to manage LEFP, but both are associated with low adherence. Calf
      muscle pump (CMP) stimulation is an alternative and more convenient approach.
      Convenience sampling was used to recruit 11 participants between ages 45 and 65
      with poor sleep quality. A within-person single-group pre-test-post-test design
      was used to evaluate changes in sleep quality, daytime sleepiness, and functional
      outcomes sensitive to impaired sleep as measured by the Pittsburgh Sleep Quality
      Index (PSQI), Functional Outcomes of Sleep Questionnaire, and Epworth Sleepiness
      Scale after 4 weeks of CMP stimulation. Statistical analysis included effect size
      (ES) calculations. After daily use of CMP stimulation, participants demonstrated
      improvement in overall sleep quality (ES = -.97) and a large reduction in daily
      disturbance from poor sleep (ES = -1.25). Moderate improvements were observed in
      daytime sleepiness (ES = -.53) and functional outcomes sensitive to sleepiness
      (ES = .49). Although causality could not be determined with this study design,
      these results support further research to determine whether CMP stimulation can
      improve sleep quality. (c) 2016 Wiley Periodicals, Inc.

PMID- 27686227
TI  - Synergistic Coordination and Hydrogen Bonding Interaction Modulate the Emission
      of Iridium Complex for Highly Sensitive Glutamine Imaging in Live Cells.
AB  - Highly selective detection of intracellular glutamine (Gln) is very essential to
      understand the roles of Gln in some biological processes. Here, we report a new
      fluorescent method for selective imaging of Gln in live cells with an aldehyde
      containing iridium complex, [Ir(pba)2(DMSO)2]PF6 (Hpba = 4-(2
      pyridiyl)benzaldehyde) (Ir1), as the probe. Density functional theory (DFT)
      calculation and experimental results suggest that the coordination and hydrogen
      bonding interaction between Ir1 and Gln synergistically stabilize the Ir1-Gln
      complex, modulate charge-transfer characteristics and emission of Ir1, and as a
      consequence, enable Ir1 as the probe for the fluorescent sensing of Gln. The
      sensing strategy is well-responsive to Gln without interference from other amino
      acids or Gln-containing peptides and is demonstrated to be useful for in situ Gln
      imaging in live cells. The study provides a new method for fluorescent imaging of
      Gln in live cells, which is envisioned to find interesting applications in
      understanding the roles of Gln in some physiological processes.

PMID- 27686228
TI  - The UCA1/miR-204/Sirt1 axis modulates docetaxel sensitivity of prostate cancer
      cells.
AB  - PURPOSE: In this study, we firstly investigated the regulative effect of miR-204
      on Sirt1 expression in prostate cancer cells. Then, we examined whether miR-204
      downregulation in the cells is a result of UCA1 upregulation. In addition, the
      regulative effect of UCA1/miR-204/Sirt1 axis on docetaxel sensitivity of prostate
      cancer cells was studied. METHODS: QRT-PCR was performed to detect UCA1, miR-204
      and Sirt1 mRNA expression. Western blot assay was performed to assess Sirt1, P-gp
      and caspase-3 expression. The regulative effect of UCA1/miR-204/Sirt1 axis on
      docetaxel sensitivity of prostate cancer cells was examined by measurement of
      docetaxel IC50, dictation of cleaved caspase-3 and flow cytometric analysis of
      cell apoptosis. RESULTS: MiR-204 negatively modulated Sirt1 expression in
      prostate cancer cells. UCA1 upregulation directly resulted in decreased miR-204
      expression. UCA1 overexpression resulted in increased Sirt1 expression in PNT2
      cells, while knockdown of endogenous UCA1 led to decreased Sirt1 in LNCaP and
      22RV1 cells. UCA1 siRNA, Sirt1 siRNA and miR-204 mimics could enhance docetaxel
      induced activation of caspase-3 and cell apoptosis in 22RV1/DR cells.
      CONCLUSIONS: There is a UCA1/miR-204/Sirt1 axis in LNCaP and 22RV1 cells. The
      UCA1/miR-204/Sirt1 axis plays an important role in modulating in vitro docetaxel
      sensitivity of the prostate cancer cells.

PMID- 27686229
TI  - [Not Available].

PMID- 27686230
TI  - Correlation of blood biomarkers with age informs pathomechanisms in succinic
      semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism.
AB  - We hypothesized that blood levels of gamma-aminobutyric acid (GABA) and gamma
      hydroxybutyric acid (GHB), biomarkers of succinic semialdehyde dehydrogenase
      deficiency (SSADHD), would correlate with age. GABA and GHB were quantified in
      plasma and red blood cells (RBCs) from 18 patients (age range 5-41 years; median
      8). Both metabolites negatively correlated with age (P < 0.05). Plasma and RBC
      GHB declined with age, reaching a nadir and approximate steady state by 10 years.
      Declining plasma GABA achieved this approximate steady state at 30-40 years of
      age. These biomarker relationships may reflect further GABA- and GHB-ergic
      neurotransmission imbalances that correlate with the onset of
      adolescent/adulthood neuropsychiatric morbidity and epilepsy in SSADHD.

PMID- 27686231
TI  - Stereotactic body radiotherapy in non-operable lung cancer patients.

PMID- 27686232
TI  - Predictive Value of C-Reactive Protein for Complications Post-Laparoscopic Roux
      En-Y Gastric Bypass.
AB  - BACKGROUND: Laparoscopic roux-en-Y gastric bypass (LRYGB) has gained increasing
      popularity as the primary procedure of choice for the management of patients with
      morbid obesity. Despite the advances, a few patients will still develop
      complications and predicting these early complications in morbidly obese patients
      can prove to be difficult. Radiological investigations have limited diagnostic
      value and have associated side effects and cost. We propose that C-reactive
      protein (CRP) is a useful predictor for early postoperative complications. This
      study aims to determine the ability of CRP taken on postoperative day 1 (POD 1)
      and 2 to predict occurrence of complications within 30 days of surgery. METHODS:
      This retrospective observational study selected 183 consecutive patients from the
      York bariatric database between 01 December 2010 and 23 March 2015. EXCLUSIONS:
      Patients undergoing dual procedures, conversion to open, and if no postoperative
      CRP measurement was performed. RESULTS: In total, 138 patients satisfied the
      inclusion criteria during the study period (median age 44 years [20-68], BMI 50.6
      kg/m2 [38.3-62.5]). Fifteen (10.8 %) patients had minor complications (CD of 2)
      and 8 (5.6 %) had major complications (CD 3 or above). A CRP of greater than 127
      mg/L on POD 2 was found to predict complications with 93 % sensitivity and 64 %
      specificity with diagnostic accuracy 0.82 (95 % confidence interval 0.731-0.908).
      CONCLUSIONS: In our patients, CRP on POD 2 has been shown to be a good predictor
      of both minor and major complications and can therefore be used to guide
      clinicians in making decision as to which patients may need further investigation
      or who can be safely discharged.

PMID- 27686233
TI  - The Impact of Biliopancreatic Diversion with Duodenal Switch (BPD/DS) Over 9
      Years.
AB  - BACKGROUND: There is limited information on the multiple long-term effects of the
      biliopancreatic diversion with duodenal switch (BPD/DS). METHODS: Patients who
      consented to a BPD/DS from 1999 to 2010 were evaluated for weight change,
      complications, comorbidity resolution, body composition, quality of life, and
      depressive symptoms during visits at 1, 3,5, 7, and 9 years. Descriptive
      statistics, analysis of variance, and pair-wise comparisons were calculated for
      each of the five follow-up cohorts vs. the baseline cohort. RESULTS: Between 1999
      and 2010, 284 patients received a BPD/DS; 275 patients (69.8 % women) age 42.7
      years, BMI 53.4 kg/m2 qualified for baseline analysis. Two hundred seventy-five
      patients were available in year 1; 275 patients in year 3; 273 patients in year
      5; 259 patients in year 7; and 228 patients in year 9. Gender distribution was
      not different. BMI was 30.1 at 1 year and 32.0 at 9 years. Body fat was reduced
      to 26 % after 2 years. Complications requiring surgery were significant.
      Nutritional problems developed in 29.8 % of patients over the course of
      observation. The baseline Beck Depression Index (BDI) was 13.9 and 7.2 in year 1.
      Year 1 through 9 remained unchanged. There were significant positive changes in
      quality of life between baseline and year 1 for most domains. These positive
      changes were maintained for the follow-up cohorts. After surgery the resolution
      of comorbidities continued for the 9 years. CONCLUSIONS: Weight loss during the
      first year was well maintained, resolving comorbidities and improving quality of
      life. Rates of surgical complications resemble other bariatric procedures. Long
      term nutrient deficiencies are of concern.

PMID- 27686234
TI  - Prospective Comparison and Quality of Life for Single-Incision and Conventional
      Laparoscopic Sleeve Gastrectomy in a Series of Morbidly Obese Patients.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy has gained a wide acceptance in the
      surgical community with an increasing popularity in the field of bariatric
      surgery. Simultaneously more surgeons have become acquainted with the single port
      techniques and sleeve gastrectomy has been regarded as an ideal field of
      application. Literature is scarce about operative and clinical outcomes of single
      port sleeve gastrectomy compared to conventional laparoscopy. The primary purpose
      of the study was to compare operative outcomes in the two study groups.
      Assessment and comparison of functional outcomes in terms of quality of life
      between groups was also performed. METHODS: Prospective data on 130 consecutive
      patients who underwent randomized SI or CL sleeve gastrectomy were collected
      between January 2009 to December 2014. Preoperative parameters, outcomes, post
      operative functional results and quality of life, according to the short-form SF
      36 questionnaire, were evaluated and compared between groups. RESULTS: 65
      patients underwent conventional laparoscopic (CL) and 65 single incision (SI)
      sleeve gastrectomy. Operative time, post-operative pain, in-hospital stay, and
      complications were similar in the two groups. No difference emerged with respect
      to passage of flatus and resumption of oral intake (p = NS). Cosmetic results
      were excellent in SI patients with higher satisfaction rates. Post-operative
      quality of life was significant higher compared to baseline (p < 0.05), and
      comparable between the two procedures. CONCLUSIONS: Single incision sleeve
      gastrectomy is safe, effective and comparable to the conventional laparoscopic
      technique in terms of outcomes. Post-operative quality of life is comparable
      between the two procedures.

PMID- 27686235
TI  - Prognostic factors for severe Pneumocystis jiroveci pneumonia of non-HIV patients
      in intensive care unit: a bicentric retrospective study.
AB  - BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) in non-HIV patients is still a
      challenge for intensivists. The aim of our study was to evaluate mortality
      predictors of PJP patients requiring Intensive care unit (ICU) admission.
      METHODS: Retrospectively review medical records of patients with diagnosis of PJP
      admitted to four ICUs of two academic medical centers from October 2012 to
      October 2015. RESULTS: Eighty-two patients were enrolled in the study. Overall
      hospital mortality was 75.6 %. Compared with survivors, the non-survivors had
      older age (55 +/- 16 vs. 45 +/- 17, p = 0.014), higher APACHE II score (20 +/- 5
      vs. 17 +/- 5, p = 0.01), lower white blood cell count (7.68 +/- 3.44 vs. 10.48 +/
      4.62, p = 0.005), less fever (80.6%vs. 100 %, p = 0.033), more hypotension (58.1
      % vs. 20 %, p = 0.003), more pneumomediastinum (29 % vs. 5 %, p = 0.027).
      Logistic regression analysis demonstrated that age [odds ratio (OR)1.051; 95 % CI
      1.007-1.097; p = 0.022], white blood cell count [OR 0.802; 95 % CI 0.670-0.960; p
      = 0.016], and pneumomediastinum [OR 16.514; 95 % CI 1.330-205.027; p = 0.029]
      were independently associated with hospital mortality. CONCLUSIONS: Mortality
      rate for non-HIV PJP patients requiring ICU admission was still high. Poor
      prognostic factors included age, white blood cell count and pneumomediastinum.

PMID- 27686236
TI  - Protective effects of vitamin E on sodium arsenite-induced toxicity, testicular
      measurements and histopathological studies of testes in Teddy goat bucks.
AB  - The objective of this study was to investigate the toxic effects of arsenic on
      testicular measurements and histology of adult Teddy goats bucks and to examine
      whether these toxic effects are scavenged by vitamin E. Twelve adult Teddy goat
      bucks were divided randomly into three groups, A, B and C. Group A was kept as
      control, the B was given sodium arsenite 5 mg/kg BW per day, and group C was fed
      with vitamin E 200 mg/kg BW per day + arsenic 5 mg/kg BW per day. This treatment
      was continued for 84 days. Analysis of data revealed that the testicular
      measurements (scrotal circumference, width, length and weight) were significantly
      reduced in arsenic-treated animals, whereas there were ameliorating effects of
      vitamin E on these parameters. The major histopathological changes were present
      in the form of loss of germinal epithelium, atrophy of Leydig cells and
      vacuolations. Vitamin E in combination with sodium arsenite increased the active
      spermatogenesis as well as restoration of germinal epithelium. It can be
      concluded from the present findings that sodium arsenite causes toxicity in the
      male reproductive system of Teddy goat bucks with major changes in parenchyma of
      testes. Supplementation of vitamin E has protective effects on the toxicity of
      sodium arsenite on the reproductive system of male Teddy goat bucks.

PMID- 27686237
TI  - Emotional Intelligence and Personality Traits as Predictors of Occupational
      Therapy students' Practice Education Performance: A Cross-Sectional Study.
AB  - This study investigated whether occupational therapy students' emotional
      intelligence and personality traits are predictive of specific aspects of their
      fieldwork performance. A total of 114 second and third year undergraduate
      occupational therapy students (86.6% response rate) completed the Genos Emotional
      Intelligence Inventory (Genos EI) and the Ten-Item Personality Inventory (TIPI).
      Fieldwork performance scores were obtained from the Student Practice Evaluation
      Form Revised (SPEF-R). Linear regressions were completed with the SPEF-R domains
      being the dependent variables and the Genos EI and TIPI factors being the
      independent variables. Regression analysis results revealed that the Genos EI
      subscales of Emotional Management of Others (EMO), Emotional Awareness of Others
      (EAO), Emotional Expression (EEX) and Emotional Reasoning (ERE) were significant
      predictors of various domains of students' fieldwork performance. EAO and ERE
      were significant predictors of students' Communication Skills accounting for 4.6%
      of its variance. EMO, EAO, EEX and ERE were significant predictors of students'
      Documentation Skills explaining 6.8% of its variance. EMO was a significant
      predictor of students' Professional Behaviour accounting for 3.2% of its
      variance. No TIPI factors were found to be significant predictors of the SPEF-R
      domains. Occupational therapy students' emotional intelligence was a significant
      predictor of components of their fieldwork performance while students'
      personality traits were not. The convenience sampling approach used, small sample
      size recruited and potential issue of social desirability of the self-reported
      Genos EI and TIPI data are acknowledged as study limitations. It is recommended
      that other studies be completed to investigate if any other relevant constructs
      or factors are predictive of occupational therapy students' fieldwork
      performance. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27686238
TI  - Outcomes after extended pancreatectomy in patients with borderline resectable and
      locally advanced pancreatic cancer.
AB  - BACKGROUND: In the recent International Study Group of Pancreatic Surgery (ISGPS)
      consensus on extended pancreatectomy, several issues on perioperative outcome and
      long-term survival remained unclear. Robust data on outcomes are sparse. The
      present study aimed to assess the outcome of extended pancreatectomy for
      borderline resectable and locally advanced pancreatic cancer. METHODS: A
      consecutive series of patients with primary pancreatic adenocarcinoma undergoing
      extended pancreatectomies, as defined by the new ISGPS consensus, were compared
      with patients who had a standard pancreatectomy. Univariable and multivariable
      analysis was performed to identify risk factors for perioperative mortality and
      characteristics associated with survival. Long-term outcome was assessed by means
      of Kaplan-Meier analysis. RESULTS: The 611 patients who had an extended
      pancreatectomy had significantly greater surgical morbidity than the 1217
      patients who underwent a standard resection (42.7 versus 34.2 per cent
      respectively), and higher 30-day mortality (4.3 versus 1.8 per cent) and in
      hospital mortality (7.5 versus 3.6 per cent) rates. Operating time of 300 min or
      more, extended total pancreatectomy, and ASA fitness grade of III or IV were
      associated with increased in-hospital mortality in multivariable analysis,
      whereas resections involving the colon, portal vein or arteries were not. Median
      survival and 5-year overall survival rate were reduced in patients having
      extended pancreatectomy compared with those undergoing a standard resection (16.1
      versus 23.6 months, and 11.3 versus 20.6 per cent, respectively). Older age, G3/4
      tumours, two or more positive lymph nodes, macroscopic positive resection
      margins, duration of surgery of 420 min or above, and blood loss of 1000 ml or
      more were independently associated with decreased overall survival. CONCLUSION:
      Extended resections are associated with increased perioperative morbidity and
      mortality, particularly when extended total pancreatectomy is performed.
      Favourable long-term outcome is achieved in some patients.

PMID- 27686239
TI  - Interpretation of Workplace Tests for Cannabinoids.
AB  - Workplace urine drug testing for an inactive THC metabolite is common in both
      federally regulated and non-regulated drug testing. A positive result does not
      document impairment, or even recent use, when impairment is likely the most
      important parameter being searched for by the drug testing procedure. Most
      cannabinoid testing does not detect imported synthetics. Currently, urine is the
      most widely tested matrix, but blood, plasma, oral fluid, and hair may also be
      accepted in federally regulated testing in the future. This article will discuss
      the history, the status quo, and the possible near term future of workplace
      testing for marijuana in employees.

PMID- 27686240
TI  - Sulfate metabolites as alternative markers for the detection of 4
      chlorometandienone misuse in doping control.
AB  - Sulfate metabolites have been described as long-term metabolites for some
      anabolic androgenic steroids (AAS). 4-chlorometandienone (4Cl-MTD) is one of the
      most frequently detected AAS in sports drug testing and it is commonly detected
      by monitoring metabolites excreted free or conjugated with glucuronic acid.
      Sulfation reactions of 4Cl-MTD have not been studied. The aim of this work was to
      evaluate the sulfate fraction of 4Cl-MTD metabolism by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) to establish potential long-term metabolites
      valuable for doping control purposes. 4Cl-MTD was administered to two healthy
      male volunteers and urine samples were collected up to 8 days after
      administration. A theoretical selected reaction monitoring (SRM) method working
      in negative mode was developed. Ion transitions were based on ionization and
      fragmentation behaviour of sulfate metabolites as well as specific neutral losses
      (NL of 15 Da and NL of 36 Da) of compounds with related chemical structure. Six
      sulfate metabolites were detected after the analysis of excretion study samples.
      Three of the identified metabolites were characterized by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass
      spectrometry (GC-MS/MS). Results showed that five out of the six identified
      sulfate metabolites were detected in urine up to the last collected samples from
      both excretion studies. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27686241
TI  - A synthetic three-dimensional niche system facilitates generation of functional
      hematopoietic cells from human-induced pluripotent stem cells.
AB  - BACKGROUND: The efficient generation of hematopoietic stem cells (HSCs) from
      human-induced pluripotent stem cells (iPSCs) holds great promise in personalized
      transplantation therapies. However, the derivation of functional and
      transplantable HSCs from iPSCs has had very limited success thus far. METHODS: We
      developed a synthetic 3D hematopoietic niche system comprising nanofibers seeded
      with bone marrow (BM)-derived stromal cells and growth factors to induce
      functional hematopoietic cells from human iPSCs in vitro. RESULTS: Approximately
      70 % of human CD34+ hematopoietic cells accompanied with CD43+ progenitor cells
      could be derived from this 3D induction system. Colony-forming-unit (CFU) assay
      showed that iPSC-derived CD34+ cells formed all types of hematopoietic colonies
      including CFU-GEMM. TAL-1 and MIXL1, critical transcription factors associated
      with hematopoietic development, were expressed during the differentiation
      process. Furthermore, iPSC-derived hematopoietic cells gave rise to both lymphoid
      and myeloid lineages in the recipient NOD/SCID mice after transplantation.
      CONCLUSIONS: Our study underscores the importance of a synthetic 3D niche system
      for the derivation of transplantable hematopoietic cells from human iPSCs in
      vitro thereby establishing a foundation towards utilization of human iPSC-derived
      HSCs for transplantation therapies in the clinic.

PMID- 27686242
TI  - The Lund University Checklist for Incipient Exhaustion: a prospective validation
      of the onset of sustained stress and exhaustion warnings.
AB  - BACKGROUND: The need for instruments that can assist in detecting the prodromal
      stages of stress-related exhaustion has been acknowledged. The aim of the present
      study was to evaluate whether the Lund University Checklist for Incipient
      Exhaustion (LUCIE) could accurately and prospectively detect the onset of
      incipient exhaustion and to what extent work stressor exposure and private
      burdens were associated with increasing LUCIE scores. METHODS: Using surveys,
      1355 employees were followed for 11 quarters. Participants with prospectively
      elevated LUCIE scores were targeted by three algorithms entailing 4 quarters: (1)
      abrupt onset to a sustained Stress Warning (n = 18), (2) gradual onset to a
      sustained Stress Warning (n = 42), and (3) sustained Exhaustion Warning (n = 36).
      The targeted participants' survey reports on changes in work situation and
      private life during the fulfillment of any algorithm criteria were analyzed,
      together with the interview data. Participants untargeted by the algorithms
      constituted a control group (n = 745). RESULTS: Eighty-seven percent of
      participants fulfilling any LUCIE algorithm criteria (LUCIE indication cases)
      rated a negative change in their work situation during the 4 quarters, compared
      to 48 % of controls. Ratings of negative changes in private life were also more
      common in the LUCIE indication groups than among controls (58 % vs. 29 %), but
      free-text commentaries revealed that almost half of the ratings in the LUCIE
      indication groups were due to work-to-family conflicts and health problems caused
      by excessive workload, assigned more properly to work-related negative changes.
      When excluding the themes related to work-stress-related private life
      compromises, negative private life changes in the LUCIE indication groups dropped
      from 58 to 32 %, while only a negligible drop from 29 to 26 % was observed among
      controls. In retrospective interviews, 79 % of the LUCIE indication participants
      confirmed exclusively/predominantly work stressors, while 6 % described a
      predominance of private life stressors. CONCLUSIONS: Negative changes in the work
      situation were the most prominent change related to a sustained increase in LUCIE
      scores. The findings seem to confirm that LUCIE is a potentially useful tool for
      clinical screening of incipient work-related exhaustion.

PMID- 27686243
TI  - Analysis of the predictive qualities of betting odds and FIFA World Ranking:
      evidence from the 2006, 2010 and 2014 Football World Cups.
AB  - The present study aims to investigate the ability of a new framework enabling to
      derive more detailed model-based predictions from ranking systems. These were
      compared to predictions from the bet market including data from the World Cups
      2006, 2010, and 2014. The results revealed that the FIFA World Ranking has
      essentially improved its predictive qualities compared to the bet market since
      the mode of calculation was changed in 2006. While both predictors were useful to
      obtain accurate predictions in general, the world ranking was able to outperform
      the bet market significantly for the World Cup 2014 and when the data from the
      World Cups 2010 and 2014 were pooled. Our new framework can be extended in future
      research to more detailed prediction tasks (i.e., predicting the final scores of
      a match or the tournament progress of a team).

PMID- 27686244
TI  - Physician trust and depression influence adherence to factor replacement: a
      single-centre cross-sectional study.
AB  - INTRODUCTION: Poor adherence to factor replacement therapy among patients with
      haemophilia can lead to joint bleeding and eventual disability. AIM: The aim of
      this study was to determine patient-related characteristics associated with
      adherence to factor replacement in adults with haemophilia. METHODS: Adults with
      haemophilia were recruited to participate in this cross-sectional study.
      Adherence was measured using either the Validated Hemophilia Regimen Treatment
      Adherence Scale (VERITAS)-Pro or the VERITAS-PRN questionnaire. Simple and
      multiple regression analyses that controlled for confounding were performed to
      determine the association between patient-related characteristics and adherence
      to factor replacement therapy. RESULTS: Of the 99 subjects enrolled, all were
      men; 91% had haemophilia A and 78% had severe disease. Age ranged from 18 to 62
      years. Most (95%) had functional health literacy; but only 23% were numerate.
      Mean adherence scores were 45.6 (SD 18) and 51.0 (SD 15) for those on a
      prophylactic and those on an episodic regimen, respectively, with a lower score
      indicating better adherence. On multivariable analysis, being on any chronic
      medication, longer duration followed at our haemophilia treatment centre, higher
      physician trust and better quality of life were associated with higher adherence.
      A history of depression was associated with lower adherence. CONCLUSION: Two
      potentially modifiable characteristics, physician trust and depression, were
      identified as motivator and barrier to adherence to factor replacement therapy.
      Promoting a high level of trust between the patient and the healthcare team as
      well as identifying and treating depression may impact adherence to factor
      replacement therapy and accordingly reduce joint destruction.

PMID- 27686245
TI  - Usage of personal music players in adolescents and its association with noise
      induced hearing loss: A cross-sectional analysis of Ohrkan cohort study data.
AB  - OBJECTIVE: To describe personal music player (PMP) usage among adolescents,
      sociodemographic determinants and association with audiometric notches. DESIGN:
      Audiometric evaluation to assess hearing status, and standardized questionnaires
      to evaluate PMP listening behaviors, leisure noise exposures and self-reported
      hearing loss symptoms. Sociodemographic information was collected using a parent
      questionnaire. Noise exposure by PMP usage equivalent for a 40 h week was
      estimated based on self-reported volume and duration of use. STUDY SAMPLE: A
      total of 2143 students (54% females) attending 9th grade in Regensburg, Germany,
      during 2009 to 2011. RESULTS: Overall, 85% of the students reported using PMPs.
      Exposure level exceeded 80 dB(A) in approximately one third, and 85 dB(A) in one
      quarter, of those who used PMP. An audiometric notch was found in 2.3% of
      participants, but was not significantly associated with higher PMP exposure.
      CONCLUSIONS: PMP exposure above the occupational limits of 80 and 85 dB(A) set by
      the Directive 2003/10/EC may be a risk factor for developing noise-induced
      hearing loss. Educational measures to ameliorate high risk behaviors in PMP usage
      are needed, particularly for socially disadvantaged groups.

PMID- 27686246
TI  - A review of the sentinel prey method as a way of quantifying invertebrate
      predation under field conditions.
AB  - Sentinel prey can provide a direct, quantitative measure of predation under field
      conditions. Live sentinel prey provides more realistic data but rarely allows the
      partitioning of the total predation pressure; artificial prey is less natural but
      traces left by different predators are identifiable, making it suitable for
      comparative studies. We reviewed the available evidence of the use of both types
      of invertebrate sentinel prey. Fifty-seven papers used real prey, usually
      measuring predation on a focal (often pest) species, with studies overwhelmingly
      from North America. The median predation was 25.8% d-1 . Artificial sentinel prey
      (45 papers) were used in both temperate and tropical areas, placed more above
      ground than at ground level. The most commonly used artificial prey imitated a
      caterpillar. Up to 14 predator groups were identified, registering a median of
      8.8% d-1 predation; half the studies reported only bird predation. Predation on
      real prey was higher than on artificial ones, but invertebrate predation was not
      higher than vertebrate predation. Invertertebrate but not vertebrate predation
      was negatively related to prey size. Predation near the Equator was not higher
      than at higher latitudes, nor in cultivated than noncultivated habitats. The use
      of sentinel prey is not yet standardised in terms of prey size, arrangement,
      exposure period or data reporting. Due to the simplicity and ease of use of the
      method, such standardisation may increase the usefulness of comparative studies,
      contributing to the understanding of the importance and level of predation in
      various habitats worldwide.

PMID- 27686247
TI  - Unveiling visuomotor control of bipedal stance, step by step.

PMID- 27686248
TI  - Listen to brain networks responding to placebos!

PMID- 27686249
TI  - Synaptic signalling and plasticity: emerging new players.

PMID- 27686250
TI  - Dual processing of visual rotation for bipedal stance control.
AB  - KEY POINTS: When standing, the gain of the body-movement response to a
      sinusoidally moving visual scene has been shown to get smaller with faster
      stimuli, possibly through changes in the apportioning of visual flow to self
      motion or environment motion. We investigated whether visual-flow speed similarly
      influences the postural response to a discrete, unidirectional rotation of the
      visual scene in the frontal plane. Contrary to expectation, the evoked postural
      response consisted of two sequential components with opposite relationships to
      visual motion speed. With faster visual rotation the early component became
      smaller, not through a change in gain but by changes in its temporal structure,
      while the later component grew larger. We propose that the early component arises
      from the balance control system minimising apparent self-motion, while the later
      component stems from the postural system realigning the body with gravity.
      ABSTRACT: The source of visual motion is inherently ambiguous such that movement
      of objects in the environment can evoke self-motion illusions and postural
      adjustments. Theoretically, the brain can mitigate this problem by combining
      visual signals with other types of information. A Bayesian model that achieves
      this was previously proposed and predicts a decreasing gain of postural response
      with increasing visual motion speed. Here we test this prediction for discrete,
      unidirectional, full-field visual rotations in the frontal plane of standing
      subjects. The speed (0.75-48 deg s(-1) ) and direction of visual rotation was
      pseudo-randomly varied and mediolateral responses were measured from
      displacements of the trunk and horizontal ground reaction forces. The behaviour
      evoked by this visual rotation was more complex than has hitherto been reported,
      consisting broadly of two consecutive components with respective latencies of
      ~190 ms and >0.7 s. Both components were sensitive to visual rotation speed, but
      with diametrically opposite relationships. Thus, the early component decreased
      with faster visual rotation, while the later component increased. Furthermore,
      the decrease in size of the early component was not achieved by a simple
      attenuation of gain, but by a change in its temporal structure. We conclude that
      the two components represent expressions of different motor functions, both
      pertinent to the control of bipedal stance. We propose that the early response
      stems from the balance control system attempting to minimise unintended body
      motion, while the later response arises from the postural control system
      attempting to align the body with gravity.

PMID- 27686251
TI  - Evaluation of injectable robenacoxib for the treatment of post-operative pain in
      cats: results of a randomized, masked, placebo-controlled clinical trial.
AB  - BACKGROUND: Few pharmaceuticals are registered in cats for the management of post
      operative pain and inflammation. The objective of this study was to assess the
      field efficacy and safety of an injectable formulation of the nonsteroidal anti
      inflammatory drug robenacoxib in cats undergoing surgery. The study was a multi
      center, prospective, randomized, masked, parallel-group, placebo-controlled
      clinical trial. A total of 349 cats were enrolled and underwent surgery
      comprising forelimb onychectomy, as an example of orthopedic surgery, plus either
      ovariohysterectomy or castration. All cats received butorphanol prior to
      anesthesia and forelimb four-point regional nerve blocks with bupivacaine after
      induction of general anesthesia. Cats were randomized to receive daily
      subcutaneous (s.c.) injection of robenacoxib, at a target dosage of 2.0 mg/kg (n
      = 174), or placebo (n = 175) once prior to surgery and for an additional two days
      post-operatively. RESULTS: Significantly (P = 0.037) fewer cats administered
      robenacoxib received additional analgesia rescue therapy (34 of 173, 19.7 %)
      compared to cats given placebo (73 of 175, 41.7 %). The percentage of treatment
      success was therefore 80.3 % with robenacoxib and 58.3 % with placebo. Behavior,
      posture, pain on palpation of the paw and soft tissue surgery sites, and overall
      pain were significantly (P < 0.05) improved versus placebo at various time points
      within the first 8 h in cats receiving robenacoxib. The most frequently reported
      adverse events were incision site infection/dehiscence, bleeding, vomiting,
      decreased appetite and lethargy. Frequencies of reported adverse clinical signs,
      hematology, serum chemistry and urinalysis variables, and body weight changes
      were similar between groups. There were no significant changes from baseline with
      robenacoxib in hepatic, hematological or renal clinical pathology variables.
      CONCLUSIONS: Robenacoxib by s.c. injection was effective and well tolerated in
      the control of post-operative pain associated with orthopedic, ovariohysterectomy
      and castration surgery in cats.

PMID- 27686252
TI  - Successful thrombolysis with recombinant tissue plasminogen activator after
      antagonizing dabigatran by idarucizumab: a case report.
AB  - BACKGROUND: Effective anticoagulation routinely precludes patients from receiving
      intravenous thrombolysis with recombinant tissue plasminogen activator to reverse
      severe symptoms of ischemic stroke. We report what we believe to be the first
      case of ischemic stroke successfully treated with recombinant tissue plasminogen
      activator after antagonizing dabigatran with the monoclonal antibody
      idarucizumab, recently approved worldwide. CASE PRESENTATION: A 75-year-old
      Caucasian man presented to our hospital with severe aphasia and mild hemiparesis.
      After providing written consent, he received two doses of 2.5 g of idarucizumab
      over 20 minutes followed by standard protocol in-label recombinant tissue
      plasminogen activator application. All symptoms resolved within 1 h. CONCLUSIONS:
      Applying a recombinant tissue plasminogen activator after antagonizing dabigatran
      with idarucizumab is feasible and easy to manage in an emergency room or stroke
      unit. Thus, idarucizumab represents a new therapeutic option for patients
      receiving dabigatran treatment, reestablishing their eligibility for recombinant
      tissue plasminogen activator thrombolysis.

PMID- 27686253
TI  - First detection of human parechovirus infection with diarrhoea, India.

PMID- 27686254
TI  - The poly(ADP-ribosyl)ation of FoxO3 mediated by PARP1 participates in
      isoproterenol-induced cardiac hypertrophy.
AB  - The Forkhead box-containing protein, O subfamily 3 (FoxO3) transcription factor
      negatively regulates myocardial hypertrophy, and its transcriptional activity is
      finely conditioned by diverse posttranslational modifications, such as
      phosphorylation, acetylation, ubiquitination, methylation and glycosylation.
      Here, we introduce a novel modification of the FoxO3 protein in cardiomyocytes:
      poly(ADP-ribosyl)ation (PARylation) mediated by poly(ADP-ribose) polymerase-1
      (PARP1). This process catalyzes the NAD+-dependent synthesis of polymers of ADP
      ribose (PAR) and their subsequent attachment to target proteins by PARPs. Primary
      cultured neonatal rat cardiomyocytes were incubated with isoproterenol (ISO) to
      induce hypertrophy, or were infected with recombinant adenovirus vectors
      harboring PARP1 cDNA (Ad-PARP1). Sprague-Dawley (SD) rats were treated with ISO
      to induce cardiac hypertrophy, or were injected with Ad-PARP1 into the anterior
      and posterior left ventricular walls. Cardiomyocyte surface area, the mRNA
      expression of hypertrophic biomarkers, echocardiography, morphometry of the
      hearts were measured. The PARP1 activity was tested by cellular PAR levels.
      Interactions of PARP1 and FoxO3 were investigated by co-immunoprecipitation and
      immunofluorescence technique. PARylation of FoxO3 mediated by PARP1 facilitated
      its phosphorylation at the T32, S252 and S314 sites, triggered its nucleus export
      and suppressed its transcriptional activity and target genes expression,
      ultimately inducing cardiac hypertrophy. Additionally, PARP1 silencing or
      specific inhibition by 3-Aminobenzamide (3AB) and veliparib (ABT-888) alleviated
      the inhibition of FoxO3 activity by ISO, thus suppressing ISO-induced cardiac
      hypertrophy. Our data provide the first evidence that PARP1 exacerbates cardiac
      hypertrophy by PARylation of FoxO3.

PMID- 27686255
TI  - Altered regulation of the Spry2/Dyrk1A/PP2A triad by homocysteine impairs neural
      progenitor cell proliferation.
AB  - Hyperhomocysteinemia reduces neurogenesis in the adult mouse brain. Homocysteine
      (Hcy) inhibits postnatal neural progenitor cell (NPC) proliferation by
      specifically impairing the fibroblast growth factor receptor (FGFR)-Erk1/2-cyclin
      E signaling pathway. We demonstrate herein that the inhibition of FGFR-dependent
      NPC proliferation induced by Hcy is mediated by its capacity to alter the
      cellular methylation potential. Our results show that this alteration modified
      the expression pattern and activity of Sprouty2 (Spry2), a negative regulator of
      the above mentioned pathway. Both elevated concentrations of Hcy and
      methyltransferase activity inhibition induced Spry2 promoter demethylation in NPC
      cultures leading to a sustained upregulation of the expression of Spry2 mRNA and
      protein. In addition, protein levels of two kinases responsible for Spry2
      activation/deactivation were altered by Hcy: Spry2 kinase Dyrk1A levels
      diminished while Spry2 phosphatase PP2A increased, leading to changes in the
      phosphorylation pattern, activity and stability of Spry2. In conclusion, Hcy
      inhibits NPC proliferation by indirect mechanisms involving alterations in DNA
      methylation, gene expression, and Spry2 function, causing FGFR signaling
      impairment.

PMID- 27686256
TI  - Further evidence of early development of attention to dynamic facial emotions:
      Reply to Grossmann and Jessen.
AB  - Adults exhibit enhanced attention to negative emotions like fear, which is
      thought to be an adaptive reaction to emotional information. Previous research,
      mostly conducted with static faces, suggests that infants exhibit an attentional
      bias toward fearful faces only at around 7months of age. In a recent study
      (Journal of Experimental Child Psychology, 2016, Vol. 147, pp. 100-110), we found
      that 5-month-olds also exhibit heightened attention to fear when tested with
      dynamic face videos. This indication of an earlier development of an attention
      bias to fear raises questions about developmental mechanisms that have been
      proposed to underlie this function. However, Grossmann and Jessen (Journal of
      Experimental Child Psychology, 2016, Vol. 153, pp. 149-154) argued that this
      result may have been due to differences in the amount of movement in the videos
      rather than a response to emotional information. To examine this possibility, we
      tested a new sample of 5-month-olds exactly as in the original study (Heck, Hock,
      White, Jubran, & Bhatt, 2016) but with inverted faces. We found that the fear
      bias seen in our study was no longer apparent with inverted faces. Therefore, it
      is likely that infants' enhanced attention to fear in our study was indeed a
      response to emotions rather than a reaction to arbitrary low-level stimulus
      features. This finding indicates enhanced attention to fear at 5months and
      underscores the need to find mechanisms that engender the development of emotion
      knowledge early in life.

PMID- 27686257
TI  - Nosocomial herpes simplex encephalitis: A challenging diagnosis.
AB  - Herpes simplex encephalitis (HSE) is a rare disease, but it is the most common
      form of sporadic encephalitis. HSE is transmitted through direct contact and
      developing nosocomial HSE is rarely reported in the literature. Nosocomial HSE is
      difficult to diagnose due to its non-specific clinical features. In this article,
      we present a case of nosocomial HSE that was responsible for grave consequence.
      We also explore its causes, outcome, and give recommendations to avoid such fatal
      occurrence. We stress on strict adherence to the standard precautions and
      preventive control measures.

PMID- 27686258
TI  - Understanding Technology and People Issues in Hospital Information System (HIS)
      Adoption: Case study of a tertiary hospital in Malaysia.
AB  - BACKGROUND: Hospital Information Systems (HIS) can improve healthcare outcome
      quality, increase efficiency, and reduce errors. The government of Malaysia
      implemented HIS across the country to maximize the use of technology to improve
      healthcare delivery, however, little is known about the benefits and challenges
      of HIS adoption in each institution. This paper looks at the technology and
      people issues in adopting such systems. METHODS: The study used a case study
      approach, using an in-depth interview with multidisciplinary medical team members
      who were using the system on a daily basis. A thematic analysis using Atlas.ti
      was employed to understand the complex relations among themes and sub-themes to
      discover the patterns in the data. . RESULTS: Users found the new system
      increased the efficiency of workflows and saved time. They reported less
      redundancy of work and improved communication among medical team members. Data
      retrieval and storage were also mentioned as positive results of the new HIS
      system. Healthcare workers showed positive attitudes during training and
      throughout the learning process. CONCLUSIONS: From a technological perspective,
      it was found that medical workers using HIS has better access and data management
      compared to the previously used manual system. The human issues analysis reveals
      positive attitudes toward using HIS among the users especially from the
      physicians' side.

PMID- 27686259
TI  - Local deformation fields and marginal integrity of sculptable bulk-fill, low
      shrinkage and conventional composites.
AB  - OBJECTIVE: To compare strain and displacement of sculptable bulk-fill, low
      shrinkage and conventional composites as well as dye penetration along the dentin
      restoration interface. METHODS: Modified Class II cavities (N=5/group) were
      filled with sculptable bulk-fill (Filtek Bulk Fill Posterior, 3M ESPE; Tetric
      EvoCeram Bulk Fill, Ivoclar Vivadent; fiber-reinforced EverX Posterior, GC;
      giomer Beautifil Bulk, Schofu), low-shrinkage (Kalore, GC), nanohybrid (Tetric
      EvoCeram, Ivoclar Vivadent) or microhybrid (Filtek Z250, 3M ESPE) composites.
      Strain and displacement were determined using the 3D digital image correlation
      method based on two cameras with 1MUm displacement sensitivity and 1600*1200
      pixel resolution (Aramis, GOM). Microleakage along dentin axial and gingival
      cavity walls was measured under a stereomicroscope using a different set of teeth
      (N=8/group). Data were analyzed using analyses of variance with Tukey's post
      test, Pearson correlation and paired t-test (alpha=0.05). RESULTS: Strain of TEC
      Bulk, Filtek Bulk, Beautifil Bulk and Kalore was in the range of 1-1.5%. EverX
      and control composites showed 1.5-2% strain. Axial displacements were between
      5MUm and 30MUm. The least strain was identified at 2mm below the occlusal surface
      in 4-mm but not in 2-mm layered composites. Greater microleakage occurred along
      the gingival than axial wall (p<0.05). No correlation was found between
      strain/displacements and microleakage axially (r2=0.082, p=0.821; r2=-0.2,
      p=0.605, respectively) or gingivally (r2=-0.126, p=0.729, r2=-0.278, p=0.469,
      respectively). SIGNIFICANCE: Strain i.e. volumetric shrinkage of sculptable bulk
      fill and low-shrinkage composites was comparable to control composites but strain
      distribution across restoration depth differed. Marginal integrity was more
      compromised along the gingival than axial dentin wall.

PMID- 27686260
TI  - Bioactivity and biocompatibility of two fluoride containing bioactive glasses for
      dental applications.
AB  - OBJECTIVE: Bioactive glasses (BAG) form, in contrast to formerly used implant
      materials, a stable bond with tissues, especially bone, when implanted. Nowadays
      BAGs are often mixed with a cement/composite that hardens in situ to broaden its
      applications in dentistry or orthopedics. The bioactivity and biocompatibility of
      possible BAG candidates for BAG-cement/composite development were evaluated.
      METHODS: Two fluoride containing BAGs were tested: a Na+-containing (45S5F),
      based on the first commercial BAG, and a Na+-free BAG (CF9), with a higher Ca2+
      and PO43- content. BAGs were tested on their bioactivity upon immersion in SBF
      for 7days by evaluating the surface changes by FT-IR, SEM, EDS and PO43- and Ca2+
      uptake and/or release from SBF. Moreover, the biocompatibility of the BAGs was
      investigated with a direct contact cell viability study with HFF cells and a cell
      adhesion study with MG-63 cells. RESULTS: The Na+-free BAG, CF9, showed the
      highest potential to bioactivate cements because of its high Ca2+-release and
      apatite (Ap) formation, as evidenced by SEM pictures and corresponding EDX
      patterns. FT-IR confirmed the formation of an Ap layer. Moreover CF9 had a higher
      biocompatibility than 45S5F. SIGNIFICANCE: For the bioactivation of
      GICs/composites in order to enhance bonding and remineralization of surrounding
      tissues, fluoride containing BAG may have advantages over other BAGs as a more
      stable fluorapatite can be formed. CF9 may be an excellent candidate therefore.

PMID- 27686261
TI  - Down the Rabbit Hole-Carrots, Genetics and Art.
AB  - The recent carrot genome assembly provides insight into carotenoid accumulation
      in carrots, and allows-together with other genetic information-to provide a
      molecular explanation for color differences observed in carrots painted
      throughout the centuries.

PMID- 27686262
TI  - Susceptibility of Grapholita molesta (Busck, 1916) to formulations of Bacillus
      thuringiensis, individual toxins and their mixtures.
AB  - The Oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae), is a
      major pest of fruit trees worldwide, such as peach and apple. Bacillus
      thuringiensis has been shown to be an efficient alternative to synthetic
      insecticides in the control of many agricultural pests. The objective of this
      study was to evaluate the effectiveness of B. thuringiensis individual toxins and
      their mixtures for the control of G. molesta. Bioassays were performed with
      Cry1Aa, Cry1Ac, Cry1Ca, Vip3Aa, Vip3Af and Vip3Ca, as well as with the commercial
      products DiPel(r) and XenTari(r). The most active proteins were Vip3Aa and
      Cry1Aa, with LC50 values of 1.8 and 7.5ng/cm2, respectively. Vip3Ca was nontoxic
      to this insect species. Among the commercial products, DiPel(r) was slightly, but
      significantly, more toxic than XenTari(r), with LC50 values of 13 and 33ng
      commercial product/cm2, respectively. Since Vip3A and Cry1 proteins are expressed
      together in some insect-resistant crops, we evaluated possible synergistic or
      antagonistic interactions among them. The results showed moderate to high
      antagonism in the combinations of Vip3Aa with Cry1Aa and Cry1Ca.

PMID- 27686263
TI  - DNA repair genes polymorphisms and risk of colorectal cancer in Saudi patients.
AB  - BACKGROUND AND STUDY AIMS: Polymorphisms in the DNA repair genes may influence
      individual capacity to repair DNA damage, which may be associated with increased
      genetic instability and carcinogenesis. Our aim was to evaluate the relation of
      genetic polymorphisms in 2 DNA repair genes, XPD Lys751Gln and XRCC1 (A399G),
      with colorectal cancer (CRC) susceptibility. We further investigated the
      potential effect of these DNA repair variants on clinicopathological parameters
      of CRC patients. PATIENTS AND METHODS: Both XPD and XRCC1 polymorphisms were
      characterised in one hundred CRC patients and one hundred healthy controls who
      had no history of any malignancy by polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP) method and PCR with confronting two-pair
      primers (PCR-CTPP), using DNA from peripheral blood in a case control study.
      RESULTS: Our results revealed that the frequencies of GG genotype of XRCC1 399
      polymorphism were significantly higher in the CRC patients than in the normal
      individuals (p?0.03), and did not observe any association between the XPD
      Lys751Gln polymorphism and CRC risk. We found association between both XRCC1
      A399G polymorphisms and histological grading of disease. CONCLUSION: Our results
      suggested that, XRCC1 gene is an important candidate gene for susceptibility to
      colorectal carcinoma.

PMID- 27686264
TI  - Single incision laparoscopic appendicectomy versus conventional three-port
      laparoscopic appendicectomy: A systematic review and meta-analysis.
AB  - BACKGROUND: Appendicectomy is a well-established surgical procedure used in the
      management of acute appendicitis. The operation can be performed with minimally
      invasive surgery or as an open procedure. A further development in the minimally
      invasive appendicectomy technique has been the introduction of single incision
      laparoscopic surgery (SILA). AIM: To ascertain any differences in outcomes from
      available trials comparing SILA with conventional multi-incision laparoscopic
      appendicectomy (CLA). METHODS: A literature search of MEDLINE/PubMed, EMBASE/Ovid
      and CENTRAL for articles from Jan1990 to June 2015 with key words:
      'appendectomy', 'appendicetomy'; 'appendicitis'; 'laparoscopy'; 'keyhole';
      'single port'; 'single incision'; 'single site'; 'one port'; 'incisionless';
      'scarless'. Randomised control trials of patients with signs and symptoms of
      appendicitis undergoing laparoscopic appendicectomy, with one arm being SILA were
      included. Statistical analysis was performed through Mantle-Haenszel and inverse
      variance methods. RESULTS: A total of 8 RCTs published between 2012 and 2014 with
      a total of 995 patients were included. Meta-analysis showed no significant
      differences between SILA and CLA for complication rates, post-operative ileus,
      length of hospital stay, return to work or post-operative pain. CLA was
      significantly superior to SILA with reduced operating time (mean difference 5.81
      [2.01, 9.62] P = 0.003) and conversion rates (OR 4.14 [1.93, 8.91] P = 0.0003).
      SILA surgery had better wound cosmesis (mean difference 0.55 [0.33, 0.77] P =
      0.00001). CONCLUSION: SILA is comparable to CLA in terms of complications, post
      operative pain and recovery. Therefore, SILA could be a viable option in the
      hands of an experienced surgeons and for patients' groups who place great value
      on the final cosmetic outcome.

PMID- 27686265
TI  - In-vivo emergence of polymyxin- B-resistant Klebsiella pneumoniae in patients
      with bloodstream infections.

PMID- 27686266
TI  - Optimizing antibiotic usage in hospitals: a qualitative study of the perspectives
      of hospital managers.
AB  - BACKGROUND: Antibiotic optimization in hospitals is an increasingly critical
      priority in the context of proliferating resistance. Despite the emphasis on
      doctors, optimizing antibiotic use within hospitals requires an understanding of
      how different stakeholders, including non-prescribers, influence practice and
      practice change. AIM: This study was designed to understand Australian hospital
      managers' perspectives on antimicrobial resistance, managing antibiotic
      governance, and negotiating clinical vis-a-vis managerial priorities. METHODS:
      Twenty-three managers in three hospitals participated in qualitative semi
      structured interviews in Australia in 2014 and 2015. Data were systematically
      coded and thematically analysed. FINDINGS: The findings demonstrate, from a
      managerial perspective: (1) competing demands that can hinder the prioritization
      of antibiotic governance; (2) ineffectiveness of audit and monitoring methods
      that limit rationalization for change; (3) limited clinical education and
      feedback to doctors; and (4) management-directed change processes are constrained
      by the perceived absence of a 'culture of accountability' for antimicrobial use
      amongst doctors. CONCLUSION: Hospital managers report considerable structural and
      interprofessional challenges to actualizing antibiotic optimization and
      governance. These challenges place optimization as a lower priority vis-a-vis
      other issues that management are confronted with in hospital settings, and
      emphasize the importance of antimicrobial stewardship (AMS) programmes that
      engage management in understanding and addressing the barriers to change.

PMID- 27686267
TI  - Vaccine profile of PPV23: Beijing Minhai Biotech 23-valent pneumococcal vaccine.
AB  - INTRODUCTION: Diseases caused by Streptococcus pneumoniae are a major public
      health problem worldwide, which can be effectively prevented by the 23-valent
      pneumococcal polysaccharide vaccines (PPV23). Areas covered: The Beijing Minhai
      PPV23 showed good safety and immunogenicity profiles in clinical trials. The
      immunogenicity of Beijing Minhai PPV23 was non-inferior to other licensed PPVs.
      Although PPV23 has been proved to be highly efficient and cost-effective, and was
      recommended for vaccination in high-risk populations in industrialized countries,
      the coverage of PPV23 vaccination was relatively low in developing countries.
      Expert commentary: The low vaccination proportions of PPV23 in China have not
      been improved in recent decades. Most of the populations with indications for
      receiving PPV23 were not aware of the possible benefits of PPV23. Moreover, PPV23
      had some limitations, which called for the development of a new generation of
      vaccines against pneumococcal infection.

PMID- 27686268
TI  - Symplocos cochinchinensis enhances insulin sensitivity via the down regulation of
      lipogenesis and insulin resistance in high energy diet rat model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This plant has been utilized in Indian system of
      medicine for treatment of diabetes. This is clearly evident from the composition
      of Ayurvedic preparation for diabetes 'Nisakathakadi Kashayam' where this is one
      of the main ingredients of this preparation AIM OF THE STUDY: The study aims in
      elucidating the molecular mechanisms underlying the insulin sensitizing effects
      of Symplocos cochinchinensis ethanol extract (SCE) using a high fructose and
      saturated fat (HFS) fed insulin resistant rat model. MATERIALS AND METHODS:
      Experimental groups consisted of normal diet (ND), ND+SCE 500mg/kg bwd,
      HFS+vehicle, HFS+metformin 100mg/kg bwd, HFS+SCE 250/500mg/kg bwd. Initially the
      animals were kept under HFS diet for 8 weeks, and at the end of 8 week period,
      animals were found to develop insulin resistance and dyslipidemia. Post
      administration of SCE, metformin or vehicle were carried out for 3 weeks. Gene
      and protein expressions relevant to insulin signalling pathway were analysed.
      RESULTS: HFS significantly altered the normal physiology of animals via proteins
      and genes relevant to metabolism like stearoyl-CoA desaturase (SCD1), sterol
      regulatory element binding protein 1 (SREBP-1c), fatty acid synthase (FAS),
      glucose 6 phosphatase (G6Pase), phosphoenol pyruvate carboxykinase (PEPCK),
      glucose transporter 2 (GLUT2), protein tyrosine phosphatse 1B (PTP1B), peroxisome
      proliferator activated receptor alpha (PPAR alpha), sirtuin 1 (SIRT1) and
      glucokinase. SCE administration attenuates the insulin resistance in HFS rat by
      the down regulation of SCD1 gene expression that modulates SREBP-1c dependent and
      independent hepatic lipid accumulation. CONCLUSION: SCE enhances insulin
      sensitivity via the down regulation of lipogenesis and insulin resistance in HFS
      rat model.

PMID- 27686269
TI  - Phytochemical and ethnomedicinal study of Huperzia species used in the
      traditional medicine of Saraguros in Southern Ecuador; AChE and MAO inhibitory
      activity.
AB  - ETHNOBOTANICAL AND ETHNOMEDICINAL RELEVANCE: This study concerns seven Huperzia
      species (Lycopodiaceae), namely H. brevifolia, H. columnaris, H. compacta, H.
      crassa, H. espinosana, H. tetragona, H. weberbaueri, which are considered sacred
      plants by the Saraguro community, living in the Southern Andes of Ecuador; these
      plants are widely used in traditional medicine and ritual ceremonies. MATERIAL
      AND METHODS: The plants were selected on the basis of written interviews with 10
      visionary healers (yachak) (2 women, 8 men), indicated as the most credible by
      the Saraguro Healers Council. The Informant Consensus Factor (Fic) was
      determined. The first phytochemical study of the plants was performed by standard
      procedures, while the AChE and MAO-A inhibition by fractions enriched in high MW
      alkaloids, was measured in vitro. AIMS OF THE STUDY: i) to investigate the uses
      of some Huperzia plants in healing and magical-religious practices of Saraguros;
      ii) to identify the main components of plant hydromethanolic extracts; iii) to
      test the effects of alkaloidal fractions on the activity of two enzymes linked to
      mental health. RESULTS: All the interviewed Saraguro yachak showed a high
      consensus about the uses of the seven Huperzia plants as purgatives and against
      supernatural diseases, such as the "espanto" (startle). In admixtures with other
      plants, some species also induce a state of trance or hallucinations in
      participants in magical-religious rituals. GC-MS of the volatile alkaloid
      fractions allowed the identification of some lycodine-type and lycopodine-type
      alkaloids (1-5) in H. compacta, H. columnaris, and H. tetragona. The flavones
      selgin) (6) and tricin (7) were isolated from H. brevifolia and H. espinosana.
      Tricin (7) was also detected in the other five species. The rare serratene
      triterpenes serratenediol (8) serratenediol-3-O-acetate (9), 21-episerratenediol
      (10), and 21-episerratenediol-3-O-acetate (11) were isolated from H. crassa. In
      addition, the presence of an unprecedented group of high molecular weight
      alkaloids has been determined. Alkaloid fractions of H. brevifolia, H. compacta,
      H. espinosana, and H. tetragona significantly inhibited AChE and MAO-A activities
      in vitro. CONCLUSIONS: The first phytochemical and ethnopharmacological study of
      seven Huperzia plants, widely used by Saraguro healers, led to the identification
      of several alkaloids and triterpenoids with different remarkable biological
      activities. In addition, alkaloid fractions exhibited a significant AChE and MAO
      A inhibitory activity. These results may support the use of these plants in brews
      prepared for inducing psychoactive effects in participants in magical-religious
      ceremonies. This study confirms the rich traditional medical knowledge of
      Saraguro healers which must be documented and preserved for future generations.

PMID- 27686270
TI  - Three indigenous plants used in anti-cancer remedies, Garcinia kola Heckel (stem
      bark), Uvaria chamae P. Beauv. (root) and Olax subscorpioidea Oliv. (root) show
      analgesic and anti-inflammatory activities in animal models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Phytochemicals with anti-oxidative and anti
      inflammatory properties are known to inhibit tumour initiation, promotion and
      progression. Hence, there is an increasingly-convincing rationale for employing
      remedies containing those phytochemicals in the treatment of cancers and also as
      analgesic and anti-inflammatory adjuvants in therapy. The plants Garcinia kola
      Heckel (Clusiaceae), stem bark; Uvaria chamae P. Beauv. (Annonaceae), root; and
      Olax subscorpioidea Oliv. (Olacaceae), root, have been documented to be part of
      various indigenous anti-cancer regimens. AIM OF THE STUDY: To determine if the
      three plants exhibit significant anti-oxidative and anti-inflammatory properties.
      MATERIALS AND METHODS: Using established models, the analgesic and anti
      inflammatory activities of the three plants were investigated. RESULTS: Pre
      treatment with the plant extracts at 100, 200 and 400mg/kg produced inhibition of
      writhes; G. kola and U. chamae showed no significant effect on formalin-induced
      pain, but O. subscorpioidea produced inhibition in both phases of the formalin
      test. Similarly, while G. kola and U. chamae did not produce any significant
      inhibitory effect in the xylene-induced ear oedema model, the oedema was
      significantly reduced by O. subscorpioidea pre-treatment. However, all the three
      plants significantly inhibited the time-dependent increase in paw circumference
      in the carrageenan- and formaldehyde-induced rat paw oedema tests, with peak
      effects observed at 400mg/kg, 6h after the induction of oedema, comparable in
      some cases to the effects of two standard drugs, the non-steroidal anti
      inflammatory drug diclofenac and the anti-inflammatory antibiotic doxycycline.
      CONCLUSION: We conclude that the three plant extracts possess analgesic and anti
      inflammatory properties, thus providing a scientific rationale for their
      inclusion in some traditional anti-cancer regimens.

PMID- 27686271
TI  - Bufalin inhibits pancreatic cancer by inducing cell cycle arrest via the c-Myc/NF
      kappaB pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bufalin, a cardiotonic steroid isolated from toad
      venom (bufo gargarizans Cantor or B. melanotictus Schneider), has widely
      demonstrated antitumor effects and exhibits potential antitumor activity in
      various human cancer cells lines. AIMS OF THE STUDY: The main characteristic of
      cancers including pancreatic cancer is the ability of uncontrolled proliferation.
      The aim of this study is to clarify the underlying mechanism by which bufalin
      inhibits pancreatic cancer cell proliferation. MATERIALS AND METHODS: The effect
      of bufalin on the suppression of tumor growth in vivo was studied in a
      bioluminescent mouse model generated using the pancreatic cancer cell line BxPC3
      luc2 and the cytotoxicity was evaluated in BcPc3 and Sw1990 cells with MTT. Flow
      cytometry and western blotting analyses were utilized to detect the effect of
      bufalin on the cell cycle and to detect the cell cycle-related proteins,
      respectively. Then, a luciferase reporter assay was applied to screen the
      activity of potent transcription factors following bufalin exposure and their
      expression was detected by western blotting. RESULTS: Bufalin suppressed tumor
      growth in a bioluminescence mouse model generated using BxPC3-luc2 cells and
      inhibited cell proliferation in vitro through inducing cell cycle arrest at S
      phase. Bufalin treatment inhibited cyclin D1 and cyclin E1 expression and
      therefore increased expression of p27, a regulatory molecular that controls cell
      cycle transition from S to G2 phase. Furthermore, luciferase reporter screening
      studies revealed that bufalin inhibited the expression and activity of the
      transcription factors c-Myc and NF-kappaB, which might cause cell cycle arrest at
      S phase and the inhibition of cell proliferation. CONCLUSIONS: Taken together,
      our results indicate that bufalin can inhibit pancreatic cancer by targeting c
      Myc, thus suggesting that the mechanism of c-Myc regulation by bufalin might be
      worthy of further study regarding its potential as a therapeutic target for
      pancreatic cancer treatment.

PMID- 27686273
TI  - Editorial commentary: Targeting Chagas disease.

PMID- 27686272
TI  - Leveraging human genetics to guide drug target discovery.
AB  - Identifying appropriate molecular targets is a critical step in drug development.
      Despite many advantages, the traditional tools of observational epidemiology and
      cellular or animal models of disease can be misleading in identifying causal
      pathways likely to lead to successful therapeutics. Here, we review some
      favorable aspects of human genetics studies that have the potential to accelerate
      drug target discovery. These include using genetic studies to identify pathways
      relevant to human disease, leveraging human genetics to discern causal
      relationships between biomarkers and disease, and studying genetic variation in
      humans to predict the potential efficacy and safety of inhibitory compounds aimed
      at molecular targets. We present some examples taken from studies of plasma
      lipids and coronary artery disease to highlight how human genetics can accelerate
      therapeutics development.

PMID- 27686274
TI  - The ordered assembly of tau is the gain-of-toxic function that causes human
      tauopathies.
AB  - A pathological pathway leading from soluble to insoluble and filamentous tau
      underlies human tauopathies. This ordered assembly causes disease and is the gain
      of-toxic function. It involves the transition from an intrinsically disordered
      monomer to a highly structured filament. Based on recent findings, one can divide
      the ordered assembly into propagation of pathology and neurodegeneration. Short
      tau fibrils constitute the major species of seed-competent tau in the brains of
      mice transgenic for human P301S tau. The molecular species of aggregated tau that
      are essential for neurodegeneration remain to be identified.

PMID- 27686275
TI  - The development of the spatially correlated adjustment wavelet filter for atomic
      force microscopy data.
AB  - In this paper a novel approach for the practical utilization of the 2D wavelet
      filter in terms of the artifacts removal from atomic force microscopy
      measurements results is presented. The utilization of additional data such as
      summary photodiode signal map is implemented in terms of the identification of
      the areas requiring the data processing, filtering settings optimization and the
      verification of the process performance. Such an approach allows to perform the
      filtering parameters adjustment by average user, while the straightforward method
      requires an expertise in this field. The procedure was developed as the function
      of the Gwyddion software. The examples of filtering the phase imaging and
      Electrostatic Force Microscopy measurement result are presented. As the wavelet
      filtering feature may remove a local artifacts, its superior efficiency over
      similar approach with 2D Fast Fourier Transformate based filter (2D FFT) can be
      noticed.

PMID- 27686276
TI  - Dependence of the volume of an antibody on the force applied in a force
      microscopy experiment in liquid.
AB  - The volume of a protein can be estimated from its molecular weight. This approach
      has also been applied in force microscopy experiments. Two factors contribute to
      the determination of the volume from a force microscope image, the applied force
      and the tip radius. Those factors act in opposite directions. Here, we
      demonstrate that in the optimum conditions to image a protein, the apparent
      volume deduced from an AFM image overestimates the real protein volume. The
      lateral broadening due to the tip finite size, makes the simulated volume to
      exceed the real protein volume value, while the force applied by the tip tends to
      decrease the measured volume. The measured volume could coincide with the real
      volume for either a point-size tip at zero force or when the compression exerted
      by the tip compensates its dilation effects. The interplay between the above
      factors make unsuitable to apply the molecular weight method to determine the
      volume of a protein from AFM data.

PMID- 27686277
TI  - Temporal course of gene expression during motor memory formation in primary motor
      cortex of rats.
AB  - Motor learning is associated with plastic reorganization of neural networks in
      primary motor cortex (M1) that depends on changes in gene expression. Here, we
      investigate the temporal profile of these changes during motor memory formation
      in response to a skilled reaching task in rats. mRNA-levels were measured 1h, 7h
      and 24h after the end of a training session using microarray technique. To assure
      learning specificity, trained animals were compared to a control group. In
      response to motor learning, genes are sequentially regulated with high time-point
      specificity and a shift from initial suppression to later activation. The
      majority of regulated genes can be linked to learning-related plasticity. In the
      gene-expression cascade following motor learning, three different steps can be
      defined: (1) an initial suppression of genes influencing gene transcription. (2)
      Expression of genes that support translation of mRNA in defined compartments. (3)
      Expression of genes that immediately mediates plastic changes. Gene expression
      peaks after 24h - this is a much slower time-course when compared to hippocampus
      dependent learning, where peaks of gene-expression can be observed 6-12h after
      training ended.

PMID- 27686278
TI  - Deficient fear extinction memory in posttraumatic stress disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) might be maintained by deficient
      extinction memory. We used a cued fear conditioning design with extinction and a
      post-extinction phase to provoke the return of fear and examined the role of the
      interplay of amygdala, hippocampus and prefrontal regions. METHODS: We compared
      18 PTSD patients with two healthy control groups: 18 trauma-exposed subjects
      without PTSD (nonPTSD) and 18 healthy controls (HC) without trauma experience.
      They underwent a three-day ABC-conditioning procedure in a functional magnetic
      resonance imaging scanner. Two geometric shapes that served as conditioned
      stimuli (CS) were presented in the context of virtual reality scenes. Electric
      painful stimuli were delivered after one of the two shapes (CS+) during
      acquisition (in context A), while the other (CS-) was never paired with pain.
      Extinction was performed in context B and extinction memory was tested in a novel
      context C. RESULTS: The PTSD patients showed significantly higher differential
      skin conductance responses than the non-PTSD and HC and higher differential
      amygdala and hippocampus activity than the HC in context C. In addition, elevated
      arousal to the CS+ during extinction and to the CS- throughout the experiment was
      present in the PTSD patients but self-reported differential valence or
      contingency were not different. During extinction recall, differential amygdala
      activity correlated positively with the intensity of numbing and ventromedial
      prefrontal cortex activity correlated positively with behavioral avoidance.
      CONCLUSIONS: PTSD patients show heightened return of fear in neural and
      peripheral measures. In addition, self-reported arousal was high to both danger
      (CS+) and safety (CS-) cues. These results suggest that a deficient maintenance
      of extinction and a failure to identify safety signals might contribute to PTSD
      symptoms, whereas non-PTSD subjects seem to show normal responses.

PMID- 27686279
TI  - Do adverse perinatal events predict mortality in schizophrenia during midlife?
AB  - BACKGROUND: We examined mortality in schizophrenia spectrum disorder (SSD) and
      non-schizophrenic psychosis (NSSD) compared to individuals without psychosis, and
      whether perinatal factors predict mortality. METHODS: Within Northern Finland
      Birth Cohort 1966 (n=10 933; 203 with SSD, 178 with NSSD), mortality was followed
      until end of 2011 by national register. Wantedness of pregnancy, mother's
      antenatal depression, smoking and age, parity, paternal socio-economic status
      (SES) and family type at birth were examined as predictors of mortality. RESULTS:
      Mortality was higher in SSD (hazard ratio (HR) 3.60; 95% confidence interval (CI)
      2.38-5.45) and NSSD (4.05; 2.65-6.17) compared to persons without psychoses after
      adjustment for gender. HR for natural death was 2.01 (0.82-4.91) in SSD and 4.63
      (2.43-8.80) in NSSD after adjustment for gender. Corresponding figures for
      unnatural deaths were 4.71 (2.94-7.54) and 2.94 (1.56-5.55), respectively. Among
      non-psychotic persons, mother's depression, smoking and low SES predicted
      mortality after adjustment for gender and parental psychoses (and SES), whereas
      among psychosis those whose father was a farmer had lower risk of mortality
      compared to those with high SES. CONCLUSIONS: Individuals with SSD had a higher
      risk of unnatural death and individuals with NSSD of natural and unnatural
      deaths. Perinatal factors seem to be more important predictors of mortality in
      individuals without psychoses than with psychoses. According to population-based
      long follow-up data, it is important to pay attention to somatic morbidity behind
      natural causes of death in psychoses and to prevent suicides in order to prevent
      excess mortality.

PMID- 27686280
TI  - Conservation and Variability of Meiosis Across the Eukaryotes.
AB  - Comparisons among a variety of eukaryotes have revealed considerable variability
      in the structures and processes involved in their meiosis. Nevertheless,
      conventional forms of meiosis occur in all major groups of eukaryotes, including
      early-branching protists. This finding confirms that meiosis originated in the
      common ancestor of all eukaryotes and suggests that primordial meiosis may have
      had many characteristics in common with conventional extant meiosis. However, it
      is possible that the synaptonemal complex and the delicate crossover control
      related to its presence were later acquisitions. Later still, modifications to
      meiotic processes occurred within different groups of eukaryotes. Better
      knowledge on the spectrum of derived and uncommon forms of meiosis will improve
      our understanding of many still mysterious aspects of the meiotic process and
      help to explain the evolutionary basis of functional adaptations to the meiotic
      program.

PMID- 27686281
TI  - The Ecology and Evolution of Cancer: The Ultra-Microevolutionary Process.
AB  - Although tumorigenesis has been accepted as an evolutionary process ( 20 , 102 ),
      many forces may operate differently in cancers than in organisms, as they evolve
      at vastly different time scales. Among such forces, natural selection, here
      defined as differential cellular proliferation among distinct somatic cell
      genotypes, is particularly interesting because its action might be thwarted in
      multicellular organisms ( 20 , 29 ). In this review, selection is analyzed in two
      stages of cancer evolution: Stage I is the evolution between tumors and normal
      tissues, and Stage II is the evolution within tumors. The Cancer Genome Atlas
      (TCGA) data show a low degree of convergent evolution in Stage I, where genetic
      changes are not extensively shared among cases. An equally important, albeit much
      less highlighted, discovery using TCGA data is that there is almost no net
      selection in cancer evolution. Both positive and negative selection are evident
      but they neatly cancel each other out, rendering total selection ineffective in
      the absence of recombination. The efficacy of selection is even lower in Stage
      II, where neutral (non-Darwinian) evolution is increasingly supported by high
      density sampling studies ( 81 , 123 ). Because natural selection is not a strong
      deterministic force, cancers usually evolve divergently even in similar tissue
      environments.

PMID- 27686282
TI  - Electrocardiographic surveillance in a psychiatric institution: avoiding
      iatrogenic cardiovascular death.
AB  - OBJECTIVE: To describe a new initiative developed to optimise patient safety in a
      mental health setting in order to prevent serious cardiac events. MATERIALS AND
      METHODS: A longitudinal study of all in-patients admitted at the hospital,
      comprised of 197 beds distributed among three units, was conducted for 12 months.
      All admitted patients at the hospital underwent electrocardiogram surveillance,
      as it was described in our new local guideline for sudden cardiac death
      prevention. When electrocardiographic alterations were detected, treating
      physicians searched for patient's risk factors and suspicious medication and
      communicated the adverse event to the Pharmacy Department. These data were
      registered in electronic medical record system. RESULTS: Over the 12-month study
      period, 225 patients were evaluated and 9 cases (4%) of long QT segment were
      detected. A multidisciplinary evaluation was done and it resulted in treatment
      modification and patient close monitoring. No sudden cardiac deaths occurred
      during the study period. Drugs more often involved in QT segment prolongation
      were: olanzapine, clomipramine, clozapine and risperidone. CONCLUSION: QT segment
      interval enlargement is a frequent clinical problem that affects patients with
      mental pathology. This inexpensive initiative has allowed identifying patients at
      risk of sudden cardiac death and has helped to avoid mayor side effects.

PMID- 27686283
TI  - Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant
      acellular Pertussis vaccine (TdaP) in healthy Thai adults.
AB  - BACKGROUND: An acellular Pertussis (aP) vaccine containing recombinant
      genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA)
      and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here
      the results of the first clinical study of this recombinant aP vaccine formulated
      alone or in combination with tetanus and diphtheria toxoids (TdaP). METHODS: A
      phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol
      University in Bangkok, Thailand in healthy adult volunteers aged 18-35 y. The
      eligible volunteers were randomized to receive one dose of either BioNet's aP or
      Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or
      the Tdap Adacel(r) vaccine in a 1:1:1 ratio. Safety follow-up was performed for
      one month. Immunogenicity was assessed at baseline, at 7 and 28 d after
      vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG
      antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed
      also by CHO cell assay. RESULTS: A total of 60 subjects (20 per each vaccine
      group) were enrolled and included in the safety analysis. Safety laboratory
      parameters, incidence of local and systemic post-immunization reactions during 7
      d after vaccination and incidence of adverse events during one month after
      vaccination were similar in the 3 vaccine groups. One month after vaccination,
      seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78%
      in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing
      antibody geometric mean titers (GMTs) were significantly higher following
      immunization with BioNet's aP and BioNet's TdaP than Adacel(r) (P< 0.05). The
      anti-PRN IgG, anti-tetanus and anti-diphtheria GMTs at one month after
      immunization were comparable in all vaccine groups. All subjects had
      seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline.
      CONCLUSION: In this first clinical study, PTgen-based BioNet's aP and TdaP
      vaccines showed a similar tolerability and safety profile to Adacel(r) and
      elicited significantly higher immune responses to PT and FHA.

PMID- 27686284
TI  - The harmonization process to set up and maintain an operational biological and
      physical retrospective dosimetry network: QA QM applied to the RENEB network.
AB  - PURPOSE: The European Network of Biological and Physical Retrospective Dosimetry
      'RENEB' has contributed to European radiation emergency preparedness. To give
      homogeneous dose estimation results, RENEB partners must harmonize their
      processes. MATERIALS AND METHODS: A first inter-comparison focused on biological
      and physical dosimetry was used to detect the outliers in terms of dose
      estimation. Subsequently, trainings were organized to improve both tools dose
      estimation. A second inter-comparison was performed to validate training
      efficiency. Simultaneously, based on ISO standards, a QA&QM manual on all
      dosimetry assays was produced which states a common basis and harmonized
      procedures for each assay. The evaluation of the agreement of RENEB partners to
      follow the QA&QM manual was performed through a questionnaire. The integration of
      new members into the network was carried out in the same way, whatever the
      assays. RESULTS: The training courses on biological and physical dosimetry were
      judged to be successful because most of the RENEB members' dose estimates
      improved in the second inter-comparison. The QA&QM manual describes the consensus
      for the minimum requirements and the performance criteria for both dosimetry
      assays. The questionnaire revealed that the whole network capacity currently can
      manage between 15 and 3800 samples once. CONCLUSION: The methodology used to
      harmonize all dosimetry practice within the network RENEB was highly successful.
      The network is operational to manage a mass casualty radiation accident for
      immediate dose assessment.

PMID- 27686285
TI  - CTHRC1 promotes angiogenesis by recruiting Tie2-expressing monocytes to
      pancreatic tumors.
AB  - CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the
      tissue-repair process, is highly expressed in several malignant tumors, including
      pancreatic cancer. We recently showed that CTHRC1 has an important role in the
      progression and metastasis of pancreatic cancer. Although CTHRC1 secretion
      affects tumor cells, how it promotes tumorigenesis in the context of the
      microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as
      a potent endothelial activator that promotes angiogenesis by recruiting bone
      marrow-derived cells to the tumor microenvironment during tumorigenesis.
      Recombinant CTHRC1 (rCTHRC1) enhanced endothelial cell (EC) proliferation,
      migration and capillary-like tube formation, which was consistent with the
      observed increases in neovascularization in vivo. Moreover, rCTHRC1 upregulated
      angiopoietin-2 (Ang-2), a Tie2 receptor ligand, through ERK-dependent activation
      of AP-1 in ECs, resulting in recruitment of Tie2-expressing monocytes (TEMs) to
      CTHRC1-overexpressing tumor tissues. Treatment with a CTHRC1-neutralizing
      antibody-abrogated Ang-2 expression in the ECs in vitro. Moreover, administration
      of a CTHRC1-neutralizing antibody to a xenograft mouse model reduced the tumor
      burden and infiltration of TEMs in the tumor tissues, indicating that blocking
      the CTHRC1/Ang-2/TEM axis during angiogenesis inhibits tumorigenesis.
      Collectively, our findings support the hypothesis that CTHRC1 induction of the
      Ang-2/Tie2 axis mediates the recruitment of TEMs, which are important for
      tumorigenesis and can be targeted to achieve effective antitumor responses in
      pancreatic cancers.

PMID- 27686286
TI  - Adsorbate-induced lifting of substrate relaxation is a general mechanism
      governing titania surface chemistry.
AB  - Under ambient conditions, almost all metals are coated by an oxide. These
      coatings, the result of a chemical reaction, are not passive. Many of them bind,
      activate and modify adsorbed molecules, processes that are exploited, for
      example, in heterogeneous catalysis and photochemistry. Here we report an effect
      of general importance that governs the bonding, structure formation and
      dissociation of molecules on oxidic substrates. For a specific example, methanol
      adsorbed on the rutile TiO2(110) single crystal surface, we demonstrate by using
      a combination of experimental and theoretical techniques that strongly bonding
      adsorbates can lift surface relaxations beyond their adsorption site, which leads
      to a significant substrate-mediated interaction between adsorbates. The result is
      a complex superstructure consisting of pairs of methanol molecules and unoccupied
      adsorption sites. Infrared spectroscopy reveals that the paired methanol
      molecules remain intact and do not deprotonate on the defect-free terraces of the
      rutile TiO2(110) surface.

PMID- 27686287
TI  - Splenorenal shunt via magnetic compression technique: a feasibility study in
      canine and cadaver.
AB  - INTRODUCTION: The concept of magnetic compression technique (MCT) has been
      accepted by surgeons to solve a variety of surgical problems. In this study, we
      attempted to explore the feasibility of a splenorenal shunt using MCT in canine
      and cadaver. MATERIAL AND METHODS: The diameters of the splenic vein (SV), the
      left renal vein (LRV), and the vertical interval between them, were measured in
      computer tomography (CT) images obtained from 30 patients with portal
      hypertension and in 20 adult cadavers. The magnetic devices used for the
      splenorenal shunt were then manufactured based on the anatomic parameters
      measured above. The observation of the anatomical structure showed there were no
      special structural tissues or any important organs between SV and LRV. Then the
      magnetic compression splenorenal shunt procedure was performed in three dogs and
      five cadavers. Seven days later, the necrotic tissue between the two magnets was
      shed and the magnets were removed with the anchor wire. RESULTS: The feasibility
      of splenorenal shunt via MCT was successfully shown in both canine and cadaver,
      thus providing a theoretical support for future clinical application.

PMID- 27686288
TI  - An urgent need for National Action Plan for Infection Control and Antibiotic
      Stewardship in Pakistan.

PMID- 27686289
TI  - Acute stroke care and long term rehabilitation in Pakistan: Challenges and
      solutions.

PMID- 27686290
TI  - Perceptions of house officers working in hospitals of Lahore about joining the
      field of anaesthesiology as a career.
AB  - OBJECTIVE: To determine the perceptions of house officers working in hospitals
      about joining anaesthesiology as a career. METHODS: This quantitative,
      descriptive questionnaire-based study was carried out from September 2014 to
      February 2015 in 26 teaching hospitals of Lahore, Pakistan, and comprised house
      officers. Those with at least three months of working experience in
      anaesthesiology were included. They were approached in their respective
      departments and a validated self-reporting questionnaire was delivered to them
      and received back by hand. SPSS 16 was used for data analysis. RESULTS: Of the 73
      house officers approached, 53(72.6%) responded; 35(66%) men and 18(33%) women.
      Overall, 25(47.16%) respondents refused to join anaesthesiology as a career and
      27(50.94%) included it in their first three career choices. Moreover, 25(47.16%)
      cited minimal interaction with patient as a reason for not taking anaesthesia as
      a career choice; 29(56.6%) of the respondents believed an anaesthetist had no or
      little role in surgery. Change in attitude about anaesthesiology as a specialty
      after having an anaesthesia rotation was mentioned by 26(49.05%) respondents.
      CONCLUSIONS: House officers had reservations about joining anaesthesiology as a
      career. The findings are suggestive of a positive effect of anaesthesiology house
      job on house officers attitude about the specialty.

PMID- 27686291
TI  - Perception of educational environment: Does it impact academic performance of
      medical students?
AB  - OBJECTIVE: To compare environmental perception as measured by the Dundee Ready
      Educational Environment Measure of students with high and low academic
      performance. METHODS: This cross-sectional analytical study was carried out at
      the Gujranwala Medical College, Gujranwala, Pakistan, and comprised medical
      students. Dundee Ready Educational Environment Measure questionnaire with 50
      items was used to determine students' perception of the institutional
      environment. Academic performance was based on mean percentage of marks obtained
      in all professional examinations. High achievers with 70% or more marks were
      compared with low achievers with <70% marks for Dundee Ready Educational
      Environment Measure scores using unpaired Student's t-test. RESULTS: Of the 180
      students, 153(85%) were included. Of them, 35(22.87%) were boys and 118(77.12%)
      girls. The overall mean Dundee Ready Educational Environment Measure score was
      116.13+/-18.24. As for the subscales, the mean score for 'perceptions of
      learning' was 27.97+/-6.0, 25.76+/-4.6 for 'perceptions of teachers', 18.67+/
      4.05 for 'academic self-perceptions', 27.76+/-6.03 for perceptions of atmosphere
      and 15.97+/-3.0 for social self-perceptions. The mean dream score was 108.51+/
      17.54 among boys and 118.39+/-17.90 among girls. The mean score for perception of
      having successful learning strategies was 1.66+/-0.9and 2.18+/-0.9 among low and
      high achievers (p>0.05) and 1.71+/-0.98 and 2.18+/-1.1 for ability to memorise
      all that was needed (p>0.05). CONCLUSIONS: Environmental perception of the
      institution was more positive than negative and better performance in
      examinations was associated with better academic self-perception and social self
      perception in students.

PMID- 27686292
TI  - Serum vitamin D levels and gene polymorphisms (Fok1 and Apa1) in children with
      type I diabetes and healthy controls.
AB  - OBJECTIVE: To compare the pattern of Vitamin D receptor (VDR) polymorphisms (Apa
      I and Fok I) in Type I Diabetes mellitus (T1DM) as cases vs healthy population as
      control and to investigate the association of VDR polymorphism with vitamin D
      levels in cases and controls. METHODS: The hypothesis of the study was "VDR gene
      polymorphisms (Fok 1 and Apa 1) and vitamin D levels are associated with the
      T1DM". The case-control study was carried out on 44 cases and 44 controls.
      Clinically diagnosed unrelated cases were recruited from the Diabetic Clinic of
      Jinnah Hospital, Lahore during Aug. 2012 to Jan 2013. Unrelated controls with
      normal glucose levels and no first-degree family history of T1DM were selected by
      convenient sampling. Vitamin D levels of both cases and controls were measured
      using Enzyme Linked Immunosorbant Assay (ELISA). Genotyping was performed by
      Restriction Fragment Length Polymorphism (RFLP)-PCR method and the data were
      analyzed statistically with IBM-SPSS 21. RESULTS: Our results demonstrated
      suboptimal vitamin D levels in whole of our sample population, whether control or
      cases (p = 0.529). There was no statistically significant difference in 25
      Hydroxyvitamin D3 levels between cases (11.351 +/- 5.92) and controls (12.335 +/-
      6.64). VDR polymorphism was not associated with susceptibility to T1DM in our
      sample population. Similarly, no association between VDR polymorphism and vitamin
      D levels was observed i.e. FokI p=0.507 and p=0.543 and ApaI p=0.986 and p=0.307
      for cases and controls respectively. CONCLUSIONS: There is an overall deficiency
      of Vitamin D levels in cases and control subjects while SNPs association studies
      suggested that in our sample population there was no association of VDR gene
      polymorphisms Fok I and Apa I with TIDM.

PMID- 27686293
TI  - Neck circumference: A supplemental tool for the diagnosis of metabolic syndrome.
AB  - OBJECTIVE: To explore the usefulness of neck circumference as a supplemental tool
      for diagnosing metabolic syndrome while identifying its cut-off values. METHODS:
      This case-control study was conducted at Dr. Essa's Laboratory and Diagnostic
      Centre, Karachi, from December 2014 to April 2015, and comprised subjects with
      and without metabolic syndrome aged between 35 and 65 years regardless of their
      diabetic status. Evaluation was done for metabolic syndrome by measuring
      anthropometric, clinical and biochemical parameters according to the criteria
      proposed by the International Diabetes Federation. Variables in both cases and
      controls were correlated with neck circumference and its cut-off values were
      determined for diagnosing metabolic syndrome. SPSS 20 was used for statistical
      analysis. RESULTS: Of the 215 subjects enrolled, 164(76.28%) were selected. Of
      them, 83(50.61%) were cases and 81(49.39%) were controls. Moreover, 90(55%) of
      them were men and 74(45%) were women. The overall mean age was 51.15+/-10.36
      years (range: 35 to 65 years).The mean neck circumference was 36.13+/-2.14 cm and
      31.59+/-1.18 cm in normal-weight men and women, respectively, compared with
      40.0+/-2.13 cm and 35.75 +/- 2.74 cm among obese men and women. The neck
      circumference correlated best with waist circumference in men (p=0.001) and with
      body surface area in women (p=0.001). The area under the curve of neck
      circumference for metabolic syndrome was 0.760 for men (p<0.001) and 0.631 for
      women (p<0.05). Optimal neck circumference cut-off points to determine metabolic
      syndrome were >38 cm for men and >34 cm for women. The odds ratio for metabolic
      syndrome was 12.44 (95% confidence interval: 4.13-37.41) among male cases and
      controls compared to 3.34 (1.26-8.80) among women. CONCLUSIONS: Neck
      circumference strongly correlated with adiposity indices and had a definite cut
      off point. It can therefore be used as a useful adjunct for clinical screening of
      metabolic syndrome.

PMID- 27686294
TI  - The effect of ethanol vapour exposure on atrial and ventricular walls of chick
      embryos.
AB  - OBJECTIVE: To study the effects of ethanol vapour exposure on atrial and
      ventricular walls of heart in chick embryo. METHODS: The study design was
      experimental, conducted at Islamabad Centre of College of Physicians and
      Surgeons, Pakistan. One hundred and eighty chicken eggs were divided into two
      groups, experimental and control, of 90 eggs each. Each group was subdivided into
      three subgroups of 30 eggs each based on the day of sacrifice. Experimental group
      was exposed to ethanol vapours and then compared with age matched controls.
      RESULTS: The thickness of atrial and ventricular walls along with lengths of
      valvular cusps increased in hearts of day 7 and day 10 chick embryos in
      experimental group. There was thinning of walls and decreased length of valvular
      cusps in hearts of experimental chicks on hatching as compared to age matched
      controls. CONCLUSIONS: Ethanol vapour exposure during development causes cardiac
      and septal wall thickening during initial days of development followed by cardiac
      and septal wall thinning which is a classical picture of alcohol induced
      cardiomyopathies.

PMID- 27686295
TI  - Prevalence of Enterococcus faecalis mediated UTI and its current antimicrobial
      susceptibility pattern in Lahore, Pakistan.
AB  - OBJECTIVE: To determine the prevalence of Enterococcus faecalis and recent trends
      in antimicrobial sensitivity profiling. METHODS: The study was conducted at
      Chughtais Lahore Lab, Lahore, Pakistan, from December 2013 to May 2014, and
      comprised urine specimens from suspected patients. Antimicrobial profiling of
      isolated strains of Enterococcus faecalis was determined by Kirby-Bauer disc
      diffusion method. RESULTS: Of the230 specimens, 161(70%) were positive for
      Enterococcus faecalis. The prevalence of Enterococcus faecalis-mediated urinary
      tract infections was 120(74.53%) in females and 41(25.46%) in males. Age-wise
      distribution of urinary tract infections among female patients was 41(34.16%) in
      >65 years age group. In males, the prevalence in the same age group was
      19(46.34%). Besides, 145(90.09%) strains of Enterococcus faecalis exhibited
      resistance to gentamicin, 140(86.95%) to norfloxacin. Moreover, 138(85.71%)
      strains exhibited multi-drug resistance. CONCLUSIONS: An overall pattern of drug
      resistance infections was observed in a majority of isolates.

PMID- 27686296
TI  - Trends of acute poisoning: 22 years experience from a tertiary care hospital in
      Karachi, Pakistan.
AB  - OBJECTIVE: To determine the trends of acute poisoning in terms of frequency,
      nature of poisoning agent, clinical presentation and its outcome. METHODS: The
      retrospective study was conducted at the Aga Khan University Hospital, Karachi,
      and comprised data of patients who presented with poisoning between January 1989
      and December 2010.The patients were randomly selected , and demographic, chemical
      information, clinical feature, treatment and outcome were analysed using SPSS 16.
      RESULTS: Of the total hospital admissions during the period, 3,189(0.3%) were
      cases of poisoning. Of them, medical records of 705(22%) cases were reviewed;
      462(65.5%) adult and 243(34.5%) paediatric cases below 16 years of age. The
      overall median age was 21 years (interquartile range: 4-32 years)Moreover,
      544(87%) were critical at the time of presentation. In 647(92%) cases, the
      poisoning occurred at home. Psychiatric drugs were found involved in 205(29%)
      cases, followed by prescription drugs 172(24.4%), pesticides 108(15.3%),
      hydrocarbons 71(10%), analgesics 59(8.7%), household toxins 59(8.7%), alcohol and
      drug abuse 21(2.97%) and others 47(6.67%). CONCLUSIONS: Poisoning was a serious
      cause of morbidity in children and young adults. Medications were the leading
      cause and home was the most common place of incident.

PMID- 27686297
TI  - Nutritional status and physical abuse among the children involved in domestic
      labour in Karachi Pakistan: a cross-sectional survey.
AB  - OBJECTIVE: To determine the prevalence of physical abuse among domestic child
      labours and to assess the nutritional status by calculating the Body Mass Index
      of children involved in domestic labour in Karachi. METHODS: A cross sectional
      study was conducted in the squatter settlements of Karachi. Questionnaire based
      interviews were conducted to capture physical abuse with 385 children who worked
      as domestic labour in the household of their employer. The ages of the children
      were between 10 to 14 years belonging to both genders. The children were enrolled
      in study by snow-ball sampling technique. RESULTS: The overall prevalence of
      physical abuse among domestic child labour in Karachi was found to be 8.3 %. Over
      9 % had low weight and about 90% were stunted. This study also highlighted that
      95% of the children involved in domestic labour perform overtime work in their
      employer's home, more than once per week. CONCLUSIONS: There is high burden of
      physical abuse among the domestic child labour and these children are
      malnourished. There is a need to recognize and regulate this form of labour in
      Pakistan.

PMID- 27686298
TI  - Association of dietary patterns with anthropometric, lifestyle and socio-economic
      factors among women of selected communities from Karachi, Pakistan.
AB  - OBJECTIVE: To identify major dietary patterns and examine their association with
      anthropometric, lifestyle and socio-economic factors among women belonging to
      different communities living in Karachi. METHODS: This cross-sectional study was
      conducted in Karachi from June 2014 to August 2015, and comprised women of Aga
      Khani, Dawoodi Bohra and Memon communities. Dietary data was collected through a
      108-item food frequency questionnaire and dietary patterns were derived by factor
      analysis. Three dietary patterns were extracted: processed, mixed and
      traditional. SPSS 20 was used for data analysis. RESULTS: Of the 322
      participants, 108(33.54%) belonged to the Aga Khani community, and 107(33.23%)
      each to Dawoodi Bohra and Memon communities. Moreover, 58(53.7%), 39(36.4%) and
      25(23.4%) in the three groups, respectively, had a university degree. Besides,
      44(40.7%) women belonging to the Aga Khani community were married, compared to
      53(49.5%) and 37(34.6%) in Dawoodi Bohra and Memon communities. The mean factor
      loading for mixed food pattern was 0.24 among women of the Aga Khani community,
      whereas respective values for Dawoodi Bohra and Memon communities were 0.005 and 
      0.25. The mean factor loading for traditional pattern was 0.77 in the Dawoodi
      Bohra community, in contrast to -0.24 and -0.52 among women belonging to Memon
      and Aga Khan communities. Processed food pattern was negatively associated with
      age in the Aga Khani community (p<0.001) and Dawoodi Bohra community (p=0.010).
      Mixed food pattern was positively associated with family size in the Aga Khani
      community (p=0.007), with watching television for 1-3 hours (p=0.007) and higher
      family income in the Dawoodi Bohra community (p=0.009). Traditional food pattern
      depicted a positive association for watching television >1-3 hours/day (p=0.028)
      and total calorie consumption/day (p=0.008) in Dawoodi Bohra community. A
      negative trend was noted for watching television (1-3 hours/day p=0.020;
      >3hours/day p=0.004) and physical inactivity (p=0.039) in the Memon community.
      CONCLUSIONS: Lifestyle and socio-economic variables were found to be associated
      with dietary patterns in all communities.

PMID- 27686299
TI  - Can dipstick method help in bacterial detection in platelet bags? A tertiary care
      hospitals blood bank review.
AB  - Objective: To find the bacterial and biochemical details of bags used in platelet
      transfusion. Methods: This cross-sectional study was carried out at a tertiary
      care hospital of Saudi Arabia (King Khalid Hospital, Najran) from January to June
      2012, and comprised platelet bags. Samples for bacterial detection and
      biochemical testing of platelet bags were taken from blood bags on Day 6 of
      donation. Bacterial detection was done by using aerobic culture bottle, different
      gram stain, cultures and analytical profile index strips. Glucose, pH and protein
      measurements were done by Multistix dipstick method. SPSS 16 was used for data
      analysis. RESULTS: Of the 352 platelet bags, 1(0.28%) showed bacterial growth on
      Day 6 of collection. That bacterium was Staphylococcus epidermidis. Glucose
      content and pH of that platelet bag was 144.14mg/dl and 5, respectively. The
      overall mean pH of platelet bags was 6.69+/-0.55 (range: 3-7). Moreover,
      255(72.4%) bags showed pH of 7, 90(25.5%) of 6, 5(1.4%) of 5 and 2(0.57%) showed
      pH of 3 on Day 6. The overall mean protein level was 6.162+/-0.204g/dl (range:
      5.8-6.6). Pearson bivariate correlation between platelet bag's pH and glucose
      content was 0.707 (p=0.001). CONCLUSIONS: Positive correlation was found between
      platelet bag's glucose and pH levels.

PMID- 27686300
TI  - The impact of hypertension on lipid parameters in type 2 diabetes.
AB  - OBJECTIVE: To study the effect of hypertension on lipid levels in patients with
      type 2 diabetes mellitus. METHODS: This prospective, observational study was
      conducted at 1 Mountain Medical Battalion, Bagh, Azad Kashmir, from May 2012 to
      April 2015, and comprised adult type 2 diabetics. Patients already on lipid
      lowering agents, hypothyroidism, nephrotic syndrome, unwilling patients and those
      who had serum triglycerides>4.5mmol/l were excluded. Blood pressure was measured
      twice in sitting position. Amongst hypertensive patients, blood pressure
      <140/90mmHg reflected good control. Serum total cholesterol, triglyceride and
      high-density lipoproteins were measured using enzymatic calorimetric method.
      Friedewald equation was used to calculate low-density lipoprotein levels.Subjects
      were divided into three groups: those without hypertension; those with
      hypertension but good blood pressure control; and hypertensives with poor blood
      pressure control. SPSS 20 was used for data analysis. RESULTS: Of the 322
      patients, 129(40.06%) were women and 193(59.94%) were men. The overall mean age
      was 51.42+/-10.93 years. Hypertension was seen in 144(44.72%) patients. Blood
      pressure was well controlled in 46(31.94%) hypertensive patients. Among patients
      without hypertension and those with good or poorly controlled blood pressure, the
      mean values for serum total cholesterol were 181.08+/- 32.05, 186.87+/- 39.00,
      185.33+/- 35.55 mg/dl, triglycerides were 172.57+/-80.53, 187.61+/-81.42,
      183.19+/-74.34 mg/dl, high-density lipoproteins were 40.54+/-12.36, 37.06+/-8.80,
      40.15+/-12.35 mg/dl and low-density lipoproteins were 105.79+/-29.73, 110.81+/
      31.66, 106.56+/-35.16 mg/dl. The number of patients with abnormalities of total
      cholesterol was 44(26.83%), 13(28.26%), 33(29.46%), triglycerides was 83(50.61%),
      30(65.22%), 66(58.93%), high-density lipoproteins was 119(72.56%), 39(84.78%),
      93(83.04%) and low-density lipoproteins was 90(54.88%), 29(63.04%) and
      59(52.68%), respectively. CONCLUSIONS: Hypertension did not worsen diabetic
      dyslipidaemia.

PMID- 27686301
TI  - Breast cancer treatment in high-risk elderly patients: A challenging situation
      and difficult decisions.
AB  - OBJECTIVE: To assess whether high-risk elderly patients with aggressive tumour
      biology can be offered standard treatment despite having multiple comorbid
      conditions. METHODS: This retrospective study was conducted at Shaukat Khanum
      Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised
      data of breast cancer patients aged 65 years or above treated between 2006 and
      2012,. Data was collected regarding patients' demographics, baseline clinical
      characteristics, comorbidities, treatment and outcomes. Stata 12 was used for
      data analysis. RESULTS: Of the 407 patients in the study, 399(98%) were women and
      8(2%) were men. The overall mean age at diagnosis was 70+/-4.9 years (range: 65
      90 years). Overall, 59(14.5%) participants had family history of breast cancer.
      Bilateral disease was seen in 17(4.2%). Invasive ductal carcinoma was seen in
      299(73.5%). Besides, 101(24.8%) patients had no comorbid conditions, while
      138(34%) had one, 102(25%) had two and 66(16%) had three or more comorbid
      conditions. There was no statistically significant difference between those
      receiving standard treatment including surgery or other modalities. CONCLUSIONS:
      Elderly patients of breast cancer may be offered treatment according to the
      tumour biology and their overall functional status.

PMID- 27686302
TI  - Age-related cataract and its types in patients with and without type 2 diabetes
      mellitus: A Hospital-based comparative study.
AB  - OBJECTIVE: To determine the frequency and types of age-related cataract in type 2
      diabetic patients compared to non-diabetics. METHODS: This comparative, cross
      sectional study was carried out at Al-Ibrahim Eye Hospital, Karachi, from July
      2014 to June 2015, and comprised both diabetics and non-diabetics. All patients
      were selected from the out-patient department and had their full ocular
      examination done, including retinal screening of diabetic patients with non
      mydriatic fundus camera. The criterion for diagnosis of cataract was sufficiently
      advanced lens opacity that caused impaired vision/un-gradable images. Cataract
      was classified on a morphological basis into cortical, nuclear, posterior sub
      capsular and mixed types. RESULTS: Of the 49,384 patients, 4,556(9.2%) were
      diabetics and 44,828(90.8%) were non-diabetics. Among the diabetics, cataract was
      found in 1,956(42.9%) compared to 7,050(15.7%) in non-diabetics. Adjusted odds
      ratio (95% confidence interval) between the two groups was 4.40 (range: 4.11
      4.71) (p<0.001). Male-to-female adjusted odds ratio (95% confidence interval) was
      2.05 (range: 1.95-2.15) (p<0.001). Nuclear sclerosis was the commonest type in
      2,123(46.6%) cataract cases in diabetics whereas posterior sub-capsular cataract
      was the commonest type in 14,480(32.3%) cases among the non-diabetics.
      CONCLUSIONS: Cataract was four times more common in diabetics and twice more
      frequent in men. Nuclear sclerosis was the commonest type of cataract in diabetic
      patients.

PMID- 27686303
TI  - Distribution and pattern of implant therapy in a part of the Turkish population.
AB  - OBJECTIVE: To report the distribution and pattern of implant replacement of
      missing tooth/teeth. METHODS: This retrospective study was conducted at the
      Suleyman Demirel University, Isparta, Turkey, and used data of patients who had
      undergone implant replacement of missing teeth/tooth from May 2008 to May 2013.
      Data analysis included age, gender, number of implants placed, implant location
      distribution, additional surgery protocol, type of dentures and failure rate.
      SPSS 12 was used for data analysis. RESULTS: A total of 843 dental implants were
      performed on 280 patients, 143(51.1%) of whom were men and 137(48.9%) women.
      Besides, 89(31.8%) of all the participants were aged between 40-49 years.
      Moreover, 218(77.9%) patients received fixed dentures and 62(22.1%) received
      overdentures. The posterior region of mandible was the location in 281(33.3%)
      implants. Bone augmentation was performed in 152(54.3%) patients. Hard tissue
      grafting with sentetic bone grafts was used in 125(63.8%) patients. Failure was
      observed in 23(2.7%) implants. CONCLUSIONS: The relationships between denture
      type and age, and denture type and additional surgery were statistically
      significant.

PMID- 27686304
TI  - Frequency of post-stroke dysphagia in Pakistan: a hospital based study.
AB  - OBJECTIVE: Purpose of the study is to determine the frequency of dysphagia after
      stroke and to see the factors associated with it. METHODS: Cross Sectional study
      design was used by including individuals pre-diagnosed as stroke on the basis of
      CT scan or MRI findings. Study was conducted in three hospitals of Lahore within
      six months. Sample size of 150 patients of any age and both gender was taken by
      using convenient sampling technique. To assess the conscious level, Glasgow coma
      scale was administered and those who scored mild or moderate on GCS were included
      in the study. Modified Massey Bedside Swallow Screener was used to screen out the
      patients for dysphagia. SPSS-19 was used for the statistical analysis. RESULTS:
      In the sample of 150 individuals with stroke 53% of patients had dysphagia.
      Females were 38% while males were 62%. Individuals who were older were more
      likely to have dysphagia. Among dysphagic individuals 65% had ischemic stroke
      while 35% were with haemorrhagic. There were 87% of dysphagic individuals who
      presented with history of smoking and 13% were without any. These factors
      demonstrate significant relationship by showing p-value <0.05. While no
      significant difference was seen between levels of alertness and risk of dyspagia
      by showing p-value 0.2. CONCLUSIONS: Dysphagia after stroke occurs frequently
      that should be actively assessed and factors like type of stroke and history of
      smoking are significantly related to this condition.

PMID- 27686305
TI  - Pioglitazone improves serum lipid profile in diet induced hyperlipidaemic non
      diabetic rats.
AB  - OBJECTIVE: To evaluate the anti-dyslipidaemic effects of pioglitazone in diet
      induced non-diabetic hyperlipidaemic rats and to compare them with gemfibrozil.
      METHODS: This comparative animal study was conducted at the Postgraduate Medical
      Institute, Lahore, Pakistan, from July to September 2011, and comprised Sprague
      Dawley albino rats divided into three equal groups. Initially all three groups
      were given high-lipid diet containing cholesterol 1.5g, coconut oil 8ml and
      sodium cholate 1.0g per 100g of rat chow to induce hyperlipidaemia. From 4th to
      8th week, Group A (control) was given 0.5ml of distilled water, Group B was given
      pioglitazone 10mg/kg body weight, and Group C was given gemfibrozil 10mg/kg body
      weight as single morning dose by oral route for a period of 04 weeks in addition
      to hyperlipidaemic diet. Serum lipid levels were estimated at zero, 4th and 8th
      week. Blood sugar level was estimated at 4th week to exclude diabetic rats.SPSS
      17 was used for data analysis. RESULTS: Of the 27 rats, each group had 9(33.33%)
      rats. At the start of the study, the mean weight was 254.44+/-14.67g in Group A,
      255.11+/-14.66g in Group B and 252.22+/-14.18g in Group C. It was 352.22+/
      16.79g, 332.22+/-17.19 and 328.11+/- 12.92 at the 8th week. The mean total
      cholesterol at 0 week was 71.4+/-4.88 mg/dl in Group A, 71.9+/-7.03 in Group B
      and 73.4+/-5.27 in Group C. At the 8th week, the values were 161.8+/-9.2 mg/dl,
      100.8+/-7.0 and 95.0+/-6.6. The mean low-density lipoproteincholesterol levels in
      the respective groups were 30.2+/-4.9mg/dl, 32.2+/-7.0 and 33.6+/-6.0 at 0 week;
      77.8+/-8.4, 85.1+/- 15.3 and 86.9+/- 6.3 at the 4th week and 113.9+/- 10.1,
      60.4+/- 9.2 (p< 0.001) and 54.8+/- 6.6 (p< 0.001) at the 8th week.The mean serum
      high-density lipoprotein cholesterol at the 8th week was 11.4+/- 1.7 mg/dl,
      19.7+/- 2.4 (p< 0.001) and 19.2+/- 2.5 (p< 0.001) in the three groups,
      respectively. CONCLUSIONS: Treatment with pioglitazone improved serum lipid
      profile of non-diabetic hyperlipidaemic rats equivalent to that of gemfibrozil.

PMID- 27686306
TI  - Antimicrobial susceptibility of bacterial and fungal infections among infected
      diabetic patients.
AB  - Objective: To determine the antimicrobial susceptibility of the most common
      bacterial and fungal infections among infected diabetic patients. Methods: This
      study was conducted at the Umm Al-Qura University, Makkah, Saudi Arabia, from
      June 2011 to June 2012, and comprised specimens collected from diabetics.
      Antibiotic susceptibility test using disc diffusion method was performed for
      bacterial isolates, and antifungal susceptibility test using colorimetric method
      for candida isolates. Results: Of the 138 specimens, antibacterial susceptibility
      test was performed for 129(93.5%) bacterial isolates while antifungal resistance
      test was performed for 9(6.5%) candida isolates. Of the bacterial isolates,
      27(20.9%) were escherichia coli, 26(20.1%) staphylococcus aureus and 15(11.6%)
      were pseudomonas aeruginosa isolates. All Escherichia coli and staphylococcus
      aureus were susceptible to amikacin and vancomycin (100% each). Moreover, all
      candida species were susceptible to amphotericin B, econazole, fluconazole,
      ketoconazole and nystatin (100% each). CONCLUSIONS: The most effective
      antibiotics for bacterial infections among diabetic patients were vancomycin for
      gram-positive bacteria, amikacin for gram-negative bacteria and for bacteria
      isolated from diabetic patients with foot infections.

PMID- 27686307
TI  - Immunohistochemical detection of FLI-1 protein expression in Ewing Sarcoma/
      peripheral primitive neuroectodermal tumour: A study of 50 cases.
AB  - OBJECTIVE: To determine friend leukaemia integration 1 transcription factor
      protein expression in cases of Ewing sarcoma. METHODS: This retrospective,
      descriptive study was conducted at the Armed Forces Institute of Pathology,
      Rawalpindi, Pakistan, and comprised data of diagnosed cases of Ewing sarcoma
      related to the period from February 2013 to December 2014. Clinico-pathological
      features, including patient age, gender and site of biopsy were studied.
      Positivity of immunohistochemical markers such as cluster of differentiation
      99(membranous staining) and Friend leukaemia integration 1 transcription factor
      (nuclear staining) were noted. SPSS17 was used for data analysis. RESULTS: Of the
      50 Ewing sarcoma cases, 26(52%) related to women and 24(48%) to men. The overall
      mean age was 17+11.53 years (range: 3 to 42 years). Moreover, 30(60%) patients
      had presented with bone swelling or growth whereas 20(40%) had presented with
      soft tissue swelling. The site of presentation was upper extremities in 16(32%)
      patients, lower extremities in 14(28%), maxilla in 7(14%), chest wall in 6(12%),
      paraspinal region in 4(8%), scalp in 2(4%) and retroperitoneum in 1(2%).
      Membranous positivity for cluster of differentiation 99 was seen in 48(98%)
      cases. Nuclear positivity for Friend leukaemia integration 1 transcription factor
      was seen in 39(78%) cases. CONCLUSIONS: Friend leukaemia integration 1
      transcription factor was found to be a useful marker in diagnosing Ewing
      sarcoma/peripheral primitive neuroectodermal tumour. However, its positivity was
      more dependable when it was used in combination with other markers such as
      cluster of differentiation 99.

PMID- 27686308
TI  - Serum YKL-40 and MDA levels in Behcet disease.
AB  - OBJECTIVE: To measure plasma levels of chitinase-3-like 1 protein and its
      association with malondialdehyde in Behcet's disease patients. METHODS: The case
      control study was conducted at Faculty of Medicine, Ataturk University Erzurum,
      Turkey, from October 2012 to March 2014, and comprised patients with Behcet's
      disease and healthy subjects. The patients were divided into two groups, as
      active and inactive, based on the classification of phases of activity in
      Behcet's disease. Differences between groups were analysed. SPSS 20 was used for
      data analysis. RESULTS: Of the 79 participants, 51(64.56%) were patients and
      28(35.44%) were controls. The mean age of the first group was 29.45+/-7.82 years
      and the second group was 32.21+/-9.61 years. Among patients, 37(72.55%) were
      categorised as "active" and 14(27.45%) as "inactive". Median serum Chitinase-3
      like 1 protein and malondialdehyde levels were 37.57 ng/mL (interquartilerange:
      13.7-293.0 ng/mL) in patients and 26.25 ng/mL (interquartile range: 17.0-44.7
      ng/mL) in controls. There was no significant correlation between Chitinase-3-like
      1 protein and malondialdehyde (p>0.05). CONCLUSIONS: Chitinase-3-like 1 protein
      might be associated with Behcet's disease. Elevated malondialdehyde levels were
      not only the cause of inflammation but also indicator of oxidative stress in
      Behcet's disease.

PMID- 27686309
TI  - Temperature on admission among cases of neonatal sepsis and its association with
      mortality.
AB  - OBJECTIVE: To ascertain the prevalence of hyperthermia and different categories
      of hypothermia among the cases of probable and culture-proven neonatal sepsis,
      and to evaluate association of mortality rate with axillary temperature at
      admission. METHODS: This analytical study was conducted at Fazl-e-Omar Hospital,
      Rabwah, Pakistan, from January to December 2013, and comprised all cases of
      culture-proven and probable neonatal sepsis admitted in the neonatal intensive
      care unit of the hospital. Using World Health Organisation classification, cases
      were categorised according to their temperature on admission, and outcome was
      recorded. SPSS 20 was used for data analysis. RESULTS: Of the 374 patients,
      47(12.6%) died. Besides, 217(58%) cases had normal temperature, 49(13.1%) had
      hyperthermia, 50(13.4%) had mild hypothermia, and 58(15.5%) had moderate
      hypothermia. Mortality rate was high among cases with mild and moderate
      hypothermia i.e. 15(32.6%) and 15(33%), compared with the mortality rate in cases
      with normal temperature i.e. 12(6.1%). Mortality rate among cases with
      hyperthermia was 5(11.6%). In early onset cases, 33(16.2%) had mild and 45(22.1%)
      had moderate hypothermia. In late onset cases, 37(21.8%) had hyperthermia.
      CONCLUSIONS: Most cases with neonatal sepsis had normal temperature. Mild and
      moderate hypothermia were found to be associated with higher mortality rate.

PMID- 27686310
TI  - Research productivity of Gulf Cooperation Council (GCC) countries in science and
      social sciences.
AB  - OBJECTIVE: To investigate the research progress of Gulf Cooperation Council
      countries in science and social sciences. METHODS: This study was conducted in
      the Department of Physiology, College of Medicine, King Saud University, Riyadh,
      Saudi Arabia, from June 2014 to February 2015.All research documents related to
      the 1996-2013 period having an affiliation with Gulf Cooperation Council
      countries, including Saudi Arabia, the United Arab Emirates, Kuwait, Qatar,
      Bahrain and Oman, were tracked. The main source for data-gathering was World
      Association of Universities, Sci-mago Journal and Country ranking and Web of
      Science Institute of Scientific Information (ISI) Thomson Reuters. RESULTS: Of
      the 544 institutions produced research papers, 141(25.92%) were universities or
      degree-awarding institutes, 372(68.38%) were research institutes and 31(5.7%)
      were Institute of Scientific Information-indexed scientific journals. The number
      of degree awarding institutes were 68(48.23%) in Saudi Arabia, 33(23.4%) in the
      United Arab Emirates and 12(8.51%) in Qatar. The total number of publications
      contributed by the region was 133638 (Mean +/- SD: 22273 +/- 26302.20); citable
      documents 127739 (Mean +/- SD: 21289.83 +/-25241.22); self-citations 105,716
      (Mean +/- SD: 17619.33 +/- 23328.44); total citations 756141 (Mean +/- SD:
      126023.5 +/- 143260.95) and citations per documents 33.22 (Mean +/- SD: 5.53 +/-
      1.09).The overall and mean Hirschindex was 513and 85.5+/- 35.39. CONCLUSIONS:
      Among Gulf Cooperation Council countries, Saudi Arabia was the most productive
      country producing adequate number of research publications, citations and holding
      the highest Hirsch index value.

PMID- 27686311
TI  - Proton pump inhibitors use; beware of side-effects.
AB  - Proton pump inhibitors are most widely prescribed medicines all over the world.
      Since their introduction in pharmacy, life of millions of people has changed
      completely. Their ability to inhibit acid secretion in stomach has changed the
      natural history of many once-dreaded conditions like peptic ulcer and
      gastroesophageal reflux disease. Operation like gastrectomy and partial
      gastrectomy are carried out very rarely. These medicines are considered very cost
      effective, have excellent safety profile, and provide prompt symptomatic relief.
      However, they are not without side effects, and several warnings have been issued
      by the Food and Drug Agency of the United States about the risk of
      hypomagnesaemia, possibility of increased fracture risk, and reduction in
      efficacy of clopidogrel by concomitant use of proton pump inhibitors. But despite
      all these warnings, their use is still on the rise. This Review was planned to
      highlight side effects and drug interactions so that a practising physician may
      keep the rare but potentially devastating effects in mind while prescribing the
      pumps.

PMID- 27686312
TI  - Domestic violence in consanguineous marriages - findings from Pakistan
      Demographic and Health Survey 2012-13.
AB  - Domestic violence is a pandemic and estimated to affect one in three women
      globally, in their lifetime. Marriages within blood relations in Pakistan are
      common. In this study a secondary analysis of Pakistan Demographic and Health
      Survey 2012-13 was done to study the prevalence and profile of domestic violence
      in the context of consanguineous marriages in Pakistan. Almost 65% of women had
      some kind of blood relationship with their husbands. Women having a blood
      relationship with husbands were more likely to report having ever been subjected
      to marital control behaviours, emotional and physical violence by their husbands,
      compared to ones without such relationship. However, these associations fail to
      reach statistical significance; underscoring the ubiquitous nature of marital
      control and violence. More effective public health education campaigns for just
      and equal treatment of wives by their husbands to speedily curb the scourge of
      domestic violence in the country are needed.

PMID- 27686313
TI  - Bilateral optic neuropathy, acral gangrene and visceral ischaemia as a rare
      presentation of calciphylaxis: A case report.
AB  - We report a case with calciphylaxis very rarely presenting with bilateral optic
      neuropathy, acral gangrene and visceral ischaemia. Bilateral papilloedaema was
      found in a 43 year-old female with chronic renal failure. Acral dry gangrene was
      observed. Pathological examination of her amputated thumb revealed calcification,
      thrombi, obstructive endovascular fibrotic areas in the walls of arteries. She
      was diagnosed with calciphylaxis. Bilateral optic neuropathy was defined
      secondary to calciphylaxis. Abdominal computerized tomography revealed prominent
      calcifications in mesenteric, spleen and renal arteries. She died eight months
      after the diagnosis. Calciphylaxis should be considered in the differential
      diagnosis of the optic neuropathy.

PMID- 27686314
TI  - Catamenial pneumothorax: A case report.
AB  - Catamenial pneumothorax (CP) is a rare and complex clinical condition caused by
      endometrial tissues, commonly found in reproductive women (age 15-49 years).Its
      diagnosis is often delayed or overlooked by clinicians, which may result in
      recurrent hospitalizations and other complications. A case of Catamenial
      pneumothorax is presented of a 38-year-old young married woman, admitted to
      hospital with signs and symptoms including chest pain and shortness of breath
      that started with her menstrual period. Right pneumothorax was observed in the
      Chest x-ray. Patient underwent Video-assisted thoracoscopic surgery (VATS).
      Patient was kept under observation, and was discharged when stable with no
      pain.Catamenial pneumothorax is still considered to be a mysterious disease and
      difficult to diagnose. Surgery is the best treatment.

PMID- 27686315
TI  - Management of Cyclops Syndrome: A case report.
AB  - Anterior Cruciate ligament (ACL) is a typical athletic injury. One of the most
      frequent complication after ACL reconstruction is reduced range of motion (ROM)
      due to the impingement on the inter-condylar notch of a fibrous tissue mass,
      defined as Cyclops Syndrome. We report the case of a 25 years old male, who
      underwent reconstruction of ACL with Gracilis-semitendinosus (GR-ST) tendons with
      delayed onset of loss of knee extension seven years after ACL reconstruction.
      Clinical and magnetic resonance image (MRI) findings were consistent with Cyclops
      syndrome. The patient underwent arthroscopy in May 2015, which revealed a fixed
      fibrous nodule impinging on the inter-condylar notch in extension that was
      treated by mechanical shaving, radiofrequency ablation remodeling inter-condylar
      notch and releasing of the ACL transplant. After surgery our patient returned to
      his routine activities after 5 days and started running about 10 days later,
      without anterior knee pain and without deficit of hyperextension.

PMID- 27686316
TI  - Alveoler process fracture in mandibular immature permanent incisors region.
AB  - The presented case evaluates the treatment of an alveolar fracture associated
      with mandibular immature lower permanent incisors. An 8-year-old girl was
      referred to our clinic 3 hours after the trauma. The clinical and radiographic
      examination of the alveoler bone showed a fracture, along with the mandibular
      fracture and significant segment mobility and dislocation of several immature
      mandibular permanent incisors. These were moving together to the lingual side
      because of the direct trauma associated with falling from the school wall. After
      the application of the buccal and lingual infiltration of local anaesthesia, the
      dislodged bone including the lower permanent incisors, were carefully
      repositioned. The teeth were splinted using semi-rigid arch bars with orthodontic
      brackets keeping the teeth between primary molars.The splints were removed one
      month later and no abnormality was observed in the immature permanent incisors.
      After 24 months follow up, the mandibular permanent incisors were observed to
      have the apical closure. Treatment of alveolar fractures in growing children with
      immature teeth may provide beneficial healing pattern with careful semi-rigid
      splinting and follow up procedures.

PMID- 27686317
TI  - Extra pancreatic solid pseudopapillary tumour in a young male.
AB  - Solid pseudo-papillary tumour of pancreas is a rare neoplasm having a low
      malignant potential. It mostly affects young adolescent females. We report an
      unusual case of an 18 year old male with a mass in the mesocolon which was
      reported as solid pseudo-papillary tumour of pancreas. This case is unusual by
      virtue of extra pancreatic location and male gender of the patient.

PMID- 27686318
TI  - Henoch-Schonlein purpura without typical lesions, presenting with
      gastrointestinal manifestations and kidney involvement following influenza - A
      case report.
AB  - We report a case of Henoch-Schonlein purpura (HSP) presenting without typical
      skin lesion; atypical symptoms initially appeared following influenza infection.
      A 4-year-old girl with influenza presented with epigastric pain and vomiting. On
      physical examination, there was epigastric tenderness, but no other signs, such
      as skin rash. On the second day, she vomited blood 10 times. Ultrasonography
      indicated focal bowel wall thickening in the right upper quadrant.
      Esophagogastroduodenoscopy showed oedematous and purpuric mucosa in the gastric
      pylorus and duodenum. Steroid therapy was initiated, and symptoms improved, but
      microscopic haematuria persisted. Even in the absence of typical purpura, if any
      gastrointestinal symptoms are observed and HSP is suspected, aggressive
      diagnostic tools must be considered, including ultrasonography or endoscopy. With
      only a few reported cases of HSP associated with influenza infection, this is the
      first reported case with gastrointestinal involvement and renal impairment, but
      without typical skin lesions.

PMID- 27686319
TI  - Choice of first injectable therapy in type 2 diabetes.
AB  - A variety of injectable therapies are now available for use in patients of type 2
      diabetes mellitus, when metformin alone proves inadequate. These injectable
      therapies include basal insulins, glucagon-like peptide 1 receptor agonists
      (GLP1RA), co-formulations of basal insulin with GLP1RA, and premixed or co
      formulated dual action insulins. This article helps choose appropriate first
      injectable therapy in a rational manner, and achieve glycaemic control in an
      efficient way. The discussion utilizes the pharmacokinetic and pharmacodynamic
      properties of various injectable drugs to match them with various clinical
      situations. It highlights a gluco-phenotypic approach, utilizing readily
      available anthropometric measurements, glycaemic patterns, and other bio
      psychosocial parameters, to create a simple model which facilitates correct
      choice of first injectable therapy in type 2 diabetes.

PMID- 27686320
TI  - Diabetes and travel.
AB  - This article encapsulates pragmatic advice that is necessary to ensure safe
      travel for people with diabetes. Written in simple words, it empowers the primary
      care physician to answer questions that are frequently asked by patients planning
      travel. It includes discussion on insulin dose adjustment, self monitoring, foot
      care and sick day management.

PMID- 27686321
TI  - Adolescent girls empowerment can save their future.

PMID- 27686322
TI  - Prevalence of Blood Lead Levels (BLLs) in children visiting tertiary care
      hospitals of Peshawar from February to April 2015: A pilot study.
AB  - OBJECTIVE: To determine blood lead level in young children visiting tertiary care
      hospitals. METHODS: This cross-sectional study was conducted from February to
      April 2015 at Khyber Teaching Hospital, Kuwait Teaching Hospital and Siffat
      Ghayoor Memorial Children's Hospital, Peshawar, Pakistan, and comprised children
      aged1-10 years. Purposive sampling technique (non-probability) was used. SPSS 17
      was used for data analysis. Charts were made in Microsoft Excel 2007. RESULTS: Of
      the 100 children in the study, 79(79%) had lead present in their blood, while
      21(21%) had no traces whatsoever. Of those who had lead in their blood, 5(6%)
      showed blood lead level of above 1 mg/dL. The overall mean blood lead level was
      0.344+/- 0.05 mg/dL. There was significance association between lead level and
      the residential areas of participants (p<0.05). CONCLUSIONS: Lead was found in
      the blood of children aged 1-10 years and was significantly related to the place
      of residence. Age and gender had no relation with blood lead levels.

PMID- 27686323
TI  - Observation of orbital two-channel Kondo effect in a ferromagnetic L10-MnGa film.
AB  - The experimental existence and stability of the fixed point of the two-channel
      Kondo (2CK) effect displaying exotic non-Fermi liquid physics have been buried in
      persistent confusion despite the intensive theoretical and experimental efforts
      in past three decades. Here we report an experimental realization of the two
      level system resonant scattering-induced orbital 2CK effect in a ferromagnetic
      L10-MnGa film, which is signified by a magnetic field-independent resistivity
      upturn that has a logarithmic and a square-root temperature dependence beyond and
      below the Kondo temperature of ~14.5 K, respectively. Our results not only
      evidence the robust existence of orbital 2CK effect even in the presence of
      strong magnetic fields and long-range ferromagnetic ordering, but also extend the
      scope of 2CK host materials from nonmagnetic nanoscale point contacts to
      diffusive conductors of disordered alloys.

PMID- 27686324
TI  - Ultraviolet-B Radiation (UV-B) Relieves Chilling-Light-Induced PSI
      Photoinhibition And Accelerates The Recovery Of CO2 Assimilation In Cucumber
      (Cucumis sativus L.) Leaves.
AB  - Ultraviolet-B radiation (UV-B) is generally considered to negatively impact the
      photosynthetic apparatus and plant growth. UV-B damages PSII but does not
      directly influence PSI. However, PSI and PSII successively drive photosynthetic
      electron transfer, therefore, the interaction between these systems is
      unavoidable. So we speculated that UV-B could indirectly affect PSI under
      chilling-light conditions. To test this hypothesis, the cucumber leaves were
      illuminated by UV-B prior or during the chilling-light treatment, and the leaves
      were then transferred to 25  degrees C and low-light conditions for recovery. The
      results showed that UV-B decreased the electron transfer to PSI by inactivating
      the oxygen-evolving complex (OEC), thereby protecting PSI from chilling-light
      induced photoinhibition. This effect advantages the recoveries of PSI and CO2
      assimilation after chilling-light stress, therefore should minimize the yield
      loss caused by chilling-light stress. Because sunlight consists of both UV-B and
      visible light, we suggest that UV-B-induced OEC inactivation is critical for
      chilling-light-induced PSI photoinhibition in field. Moreover, additional UV-B
      irradiation is an effective strategy to relieve PSI photoinhibition and yield
      loss in protected cultivation during winter. This study also demonstrates that
      minimizing the photoinhibition of PSI rather than that of PSII is essential for
      the chilling-light tolerance of the plant photosynthetic apparatus.

PMID- 27686325
TI  - Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile
      Adolescent Animal Model of Diet-Induced Obesity.
AB  - NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this
      study, we evaluated whether the cardiac protective effects of nebivolol relied on
      attenuating NLRP3 activation in a juvenile-adolescent animal model of diet
      induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard
      chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were
      subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low
      dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d).
      Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac
      lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol
      attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation
      in myocardium of obese rats. In parallel, nebivolol treatment of obese animals
      increased cardiac beta3-AR expression, reversing the reduction of endothelial
      nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate
      incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis,
      leading to decreased mitochondrial reactive oxygen species (mtROS) generation,
      and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA
      against beta3-AR or against eNOS deteriorated the protective effects of
      nebivolol. These data suggest the beneficial effect of nebivolol on myocardial
      lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly
      via improved mitochondrial dysfunction.

PMID- 27686327
TI  - How the BMA lost control of the junior doctors' dispute.

PMID- 27686326
TI  - Association of Microcirculation, Macrocirculation, and Severity of Illness in
      Septic Shock: A Prospective Observational Study to Identify Microcirculatory
      Targets Potentially Suitable for Guidance of Hemodynamic Therapy.
AB  - PURPOSE: Clinically unapparent microcirculatory impairment is common and has a
      negative impact on septic shock, but specific therapy is not established so far.
      This prospective observational study aimed at identifying candidate parameters
      for microcirculatory-guided hemodynamic therapy. ClinicalTrials.gov :
      NCT01530932. MATERIALS AND METHODS: Microcirculatory flow and postcapillary
      venous oxygen saturation were detected during vaso-occlusive testing (VOT) on
      days 1 (T0), 2 (T24), and 4 (T72) in 20 patients with septic shock at a surgical
      intensive care unit using a laser Doppler spectrophotometry system (O2C).
      RESULTS: Reperfusional maximal venous capillary oxygen saturation (SvcO2max)
      showed negative correlations with Simplified Acute Physiology Score II
      (SAPSII)/Sequential Organ Failure Assessment (SOFA) score, norepinephrine dosage,
      and lactate concentration and showed positive correlations with cardiac index
      (CI). At T24 and T72, SvcO2max was also inversely linked to fluid balance. With
      respect to any predictive value, SvcO2max and CI determined on day 1 (T0) were
      negatively correlated with SAPS II/SOFA on day 4 (T72). Moreover, SvcO2max
      measured on day 1 or day 2 was negatively correlated with cumulated fluid balance
      on day 4 ( r= -.472, P < .05 and r = -.829, P < .001). By contrast, CI neither on
      day 1 nor on day 2 was correlated with cumulated fluid balance on day 4 ( r = 
      .343, P = .17 and r = -.365, P = .15). CONCLUSION: In patients with septic shock,
      microcirculatory reserve as assessed by SvcO2max following VOT was impaired and
      negatively correlated with severity of illness and fluid balance. In contrast to
      CI, SvcO2max determined on day 1 or day 2 was significantly negatively correlated
      with cumulative fluid balance on day 4. Therefore, early microcirculatory
      measurement of SvcO2max might be superior to CI in guidance of sepsis therapy to
      avoid fluid overload. This has to be addressed in future clinical studies.

PMID- 27686328
TI  - Value and usability of unpublished data sources for systematic reviews and
      network meta-analyses.
AB  - Peer-reviewed publications and conference proceedings are the mainstay of data
      sources for systematic reviews and network meta-analyses (NMA), but access to
      informative unpublished data is now becoming commonplace. To explore the
      usefulness of three types of 'grey' literature-clinical trials registries,
      clinical study reports and data from regulatory authorities-we conducted four
      case studies. The reporting of outcome data in peer-reviewed publications, the
      clinical trials registries and the clinical study reports for two clinical trials
      one in melanoma, one in juvenile idiopathic arthritis (JIA)-was examined. In
      addition, we assessed the value of including unpublished data from the European
      Medicines Agency (EMA) and US Food and Drug Administration (FDA) in evidence
      syntheses of hepatitis C virus (HCV) and chronic obstructive pulmonary disease
      (COPD), respectively. For the clinical trials in melanoma and JIA, we identified
      outcome parameters on ClinicalTrials.gov additional to those reported in the peer
      reviewed publications: subgroup data and additional efficacy end points/extended
      follow-up, respectively. The clinical study report also provided results for
      several subgroups unavailable elsewhere. For HCV and COPD, additional outcome
      data were obtained from the EMA European Public Assessment Report (EPAR) and the
      FDA, respectively, including data on subgroups and mortality. We conclude that
      data from these grey literature sources have the potential to influence results
      of systematic reviews and NMAs, and may thus have implications for healthcare
      decisions. However, it is important to consider carefully the availability,
      reliability and consequent usability of these data sources in systematic reviews
      and NMAs.

PMID- 27686329
TI  - Heavy Metal Concentrations in some Edible Vegetables: A Case Study in Uyo and
      Ibesikpo Asutan Local Government Areas of Akwa-Ibom State.
AB  - BACKGROUND: This study assessed the level of heavy metals (Zn, Cu, Mn, Hg and Fe)
      accumulation in leaves of five vegetables viz: Telfairia occidentalis, Heinsia
      crinita, Gnetum africanum, Talinum triangulare and Vernonia amygdalina planted in
      different gardens in Ibesikpo Asutan and Uyo L.G.As in Akwa Ibom State, Nigeria
      using standard scientific methods. METHODS: Soil samples were obtained at a depth
      of 0 - 10 cm each at the base of each vegetable using soil auger. RESULTS: The
      results obtained from this study showed that the nutrient status and heavy metals
      concentrations of the soil of the two Local Government Areas were not
      significantly (P= 0.05) different. However, the levels of the heavy metals
      contents of the leaves of the vegetables were observed to fall within World
      Health Organisation (WHO) permissible concentration range. This observation
      indicated that there are little or no anthropogenic activities in or around the
      garden leading to the emission of heavy metals into the environment. Also, the
      result attributes the low heavy metals accumulation in the soil and poor
      translocation to the use of organic supplements in the gardens. CONCLUSION: The
      finding of this study certifies that there is no risk associated with the
      consumption of vegetables from these farms. This result is discussed in line with
      current global trends in pollution management and dietetics.

PMID- 27686330
TI  - Predicting episodic memory formation for movie events.
AB  - Episodic memories are long lasting and full of detail, yet imperfect and
      malleable. We quantitatively evaluated recollection of short audiovisual segments
      from movies as a proxy to real-life memory formation in 161 subjects at 15
      minutes up to a year after encoding. Memories were reproducible within and across
      individuals, showed the typical decay with time elapsed between encoding and
      testing, were fallible yet accurate, and were insensitive to low-level stimulus
      manipulations but sensitive to high-level stimulus properties. Remarkably,
      memorability was also high for single movie frames, even one year post-encoding.
      To evaluate what determines the efficacy of long-term memory formation, we
      developed an extensive set of content annotations that included actions,
      emotional valence, visual cues and auditory cues. These annotations enabled us to
      document the content properties that showed a stronger correlation with
      recognition memory and to build a machine-learning computational model that
      accounted for episodic memory formation in single events for group averages and
      individual subjects with an accuracy of up to 80%. These results provide initial
      steps towards the development of a quantitative computational theory capable of
      explaining the subjective filtering steps that lead to how humans learn and
      consolidate memories.

PMID- 27686331
TI  - A powerful weighted statistic for detecting group differences of directed
      biological networks.
AB  - Complex disease is largely determined by a number of biomolecules interwoven into
      networks, rather than a single biomolecule. Different physiological conditions
      such as cases and controls may manifest as different networks. Statistical
      comparison between biological networks can provide not only new insight into the
      disease mechanism but statistical guidance for drug development. However, the
      methods developed in previous studies are inadequate to capture the changes in
      both the nodes and edges, and often ignore the network structure. In this study,
      we present a powerful weighted statistical test for group differences of directed
      biological networks, which is independent of the network attributes and can
      capture the changes in both the nodes and edges, as well as simultaneously
      accounting for the network structure through putting more weights on the
      difference of nodes locating on relatively more important position. Simulation
      studies illustrate that this method had better performance than previous ones
      under various sample sizes and network structures. One application to GWAS of
      leprosy successfully identifies the specific gene interaction network
      contributing to leprosy. Another real data analysis significantly identifies a
      new biological network, which is related to acute myeloid leukemia. One potential
      network responsible for lung cancer has also been significantly detected. The
      source R code is available on our website.

PMID- 27686332
TI  - Can Lay Community Advisors Improve the Clarity of Research Participant
      Recruitment Materials and Increase the Likelihood of Participation?
AB  - Despite decades of effort, lower income people and ethnic minorities continue to
      be underrepresented as participants in health research. A group of racially and
      ethnically diverse, lower income community members (Community Advisors on
      Research Design and Strategies: CARDS(r)) was trained to review study designs and
      procedures and provide recommendations to researchers for increasing
      participation and making research materials more understandable to members of
      underrepresented communities. In this mixed methods study, one participant group
      (n = 55) was shown research materials (recruitment documents and a consent form)
      developed by a research team and approved by the local IRB. A second group (n =
      45) was shown the same materials after they had also been reviewed and revised by
      CARDS. Interviews, which included both fixed-response and open-ended questions,
      were used to assess reactions of participants in both groups to the materials,
      including their hypothetical willingness to volunteer for the research described.
      Group differences were examined using the Chi-square distribution test.
      Proportional difference effect sizes were estimated using arcsine transformation.
      The qualitative data were subjected to conventional content analysis.
      Participants in the group shown the recruitment materials revised by CARDS were
      more likely to say they understood the documents, more likely to ask for more
      information about the study, and more likely to say they would participate in the
      research. Results of content analysis suggested a four-phase sequential process
      for deciding whether to participate in the research. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27686333
TI  - Tapping the archives: the sterol composition of marine sponge species, as
      determined non-invasively from museum-preserved specimens, reveals
      biogeographical features.
AB  - Over 8600 species are currently recorded in the phylum Porifera (sponges). They
      produce a large diversity of biochemical compounds including sterols, with more
      than 250 different sterols identified. Some of these sterols are of great
      interest, due to their use for fingerprinting in ecological and biomarker
      (molecular fossil) studies. As a large number of identified extant species from
      biodiversity surveys are housed in museum collections, preserved in ethanol,
      these present a potentially rich source of identified specimens for comparative
      lipid analyses. Here, we show that, in at least one species, sterol distributions
      obtained from the ethanol used to preserve specimens of sponges were
      representative, and comparable to the sterol distribution obtained from wet
      frozen and from freeze-dried tissue from the same species. We employed both GC-MS
      and two-dimensional gas chromatography-time-of-flight mass spectrometry (GC*GC
      TOFMS), with an improved signal-to-noise ratio for even minor constituents.
      Analysis of two additional specimens of the same species, but of different
      provenance, resulted in detection of marked differences in sterol composition,
      which could be attributed to variations in geography, environmental conditions,
      microbial communities, diet or cryptic speciation. The possibility of using
      ethanol from identified, preserved museum sponges could drastically increase the
      number of available samples. This could enable the study of their sterol
      complements, and the detailed investigation of differences due to geographical
      and oceanographic, phylogenetic, and other factors in unprecedented detail.

PMID- 27686334
TI  - Editorial Comment from Dr Hongo to Robot-assisted partial nephrectomy confers
      excellent long-term outcomes for the treatment of complex cystic renal tumors:
      Median follow up of 58 months.

PMID- 27686335
TI  - A Stimuli-Responsive, Binary Reagent System for Rapid Isolation of Protein
      Biomarkers.
AB  - Magnetic microbeads exhibit rapid separation characteristics and are widely
      employed for biomolecule and cell isolations in research laboratories, clinical
      diagnostics assays, and cell therapy manufacturing. However, micrometer particle
      diameters compromise biomarker recognition, which leads to long incubation times
      and significant reagent demands. Here, a stimuli-responsive binary reagent system
      is presented that combines the nanoscale benefits of efficient biomarker
      recognition and the microscale benefits of rapid magnetic separation. This system
      comprises magnetic nanoparticles and polymer-antibody (Ab) conjugates that
      transition from hydrophilic nanoscale reagents to microscale aggregates in
      response to temperature stimuli. The binary reagent system was benchmarked
      against Ab-labeled Dynabeads in terms of biomarker isolation kinetics, assay
      speed, and reagent needs. Surface plasmon resonance (SPR) measurements showed
      that polymer conjugation did not significantly alter the Ab's binding affinity or
      kinetics. ELISA analysis showed that the unconjugated Ab, polymer-Ab conjugates,
      and Ab-labeled Dynabeads exhibited similar equilibrium dissociation constants
      (Kd), ~2 nM. However, the binary reagent system isolated HIV p24 antigen from
      spiked serum specimens (150 pg/mL) much more quickly than Dynabeads, which
      resulted in shorter binding times by tens of minutes, or about 30-50% shorter
      overall assay times. The binary reagent system showed improved performance
      because the Ab molecules were not conjugated to large, solid microparticle
      surfaces. This stimuli-responsive binary reagent system illustrates the potential
      advantages of nanoscale reagents in molecule and cell isolations for both
      research and clinical applications.

PMID- 27686336
TI  - Visit-to-Visit Blood Pressure Variability-What is the current challenge?

PMID- 27686337
TI  - Ascending Aortic Elasticity and Related Risk Factors Study on Prehypertension
      Patients.
AB  - BACKGROUND: A new feature of coronary computed tomography angiography (CTA) is to
      estimate ascending aortic elasticity without additional cost, but its applicable
      benefit for prehypertension patients is still unclear. The aim of this study is
      to discuss the characteristic of ascending aortic elasticity for specific
      prehypertension patients and its risk factors. METHODS: Coronary CTA examinations
      of 398 participants were performed using a 128 slicer CT scanner. The differences
      of 3 ascending aortic elasticity related indices, including aortic distensibility
      (AD), aortic compliance (AC), and aortic stiffness (ASI), and anatomical
      measurements were analyzed among the normal, prehypertension, and primary
      hypertension groups. RESULTS: No difference was found for normalized minimum
      cross-sectional diameter and area for the ascending aorta between prehypertension
      and normal groups. AD, AC, and ASI were significantly different in 3 groups.
      Between prehypertension and normal groups, AD and AC were found much smaller but
      no difference were found for ASI; while between prehypertension and hypertension
      groups, significant differences were found in AD and ASI, and AC was found to a
      lesser extent. Risk factor study for prehypertension patients indicated that age
      and systolic pressure were the independent risk factors for AD decline.
      CONCLUSION: As a byproduct, coronary CTA can provide multiple aortic elasticity
      related indices for the prehypertension patients, without additional contrast
      media consumption and radiation dose. It is proofed that the early detection of
      ascending aortic elasticity index changes, especially for AD are essential for
      identifying the high-risk individuals in the prehypertension populations.
      CLINICAL TRIALS REGISTRATION: Our public trials registry number ChiCTR-RIC
      15007482.

PMID- 27686338
TI  - Exploring second coordination sphere effects in nitric oxide synthase.
AB  - Second coordination sphere (SCS) effects in proteins are modulated by active site
      residues and include hydrogen bonding, electrostatic/dipole interactions, steric
      interactions, and pi-stacking of aromatic residues. In Cyt P450s, extended H
      bonding networks are located around the proximal cysteinate ligand of the heme,
      referred to as the 'Cys pocket'. These hydrogen bonding networks are generally
      believed to regulate the Fe-S interaction. Previous work identified the S(Cys) ->
      Fe sigma CT transition in the high-spin (hs) ferric form of Cyt P450cam and
      corresponding Cys pocket mutants by low-temperature (LT) MCD spectroscopy
      [Biochemistry 50:1053, 2011]. In this work, we have investigated the effect of
      the hydrogen bond from W409 to the axial Cys ligand of the heme in the hs ferric
      state (with H4B and L-Arg bound) of rat neuronal nitric oxide synthase oxygenase
      construct (nNOSoxy) using MCD spectroscopy. For this purpose, wt enzyme and W409
      mutants were investigated where the H-bonding network with the axial Cys ligand
      is perturbed. Overall, the results are similar to Cyt P450cam and show the
      intense S(Cys) -> Fe sigma CT band in the LT MCD spectrum at about 27,800 cm-1,
      indicating that this feature is a hallmark of {heme-thiolate} active sites. The
      discovery of this MCD feature could constitute a new approach to classify {heme
      thiolate} sites in hs ferric proteins. Finally, the W409 mutants show that the
      hydrogen bond from this group only has a small effect on the Fe-S(Cys) bond
      strength, at least in the hs ferric form of the protein studied here. Low
      temperature MCD spectroscopy is used to investigate the effect of the hydrogen
      bond from W409 to the axial Cys ligand of the heme in neuronal nitric oxide
      synthase. The intense S(Cys) -> Fe sigma-CT band is monitored to identify changes
      in the Fe-S(Cys) bond in wild-type protein and W409 mutants.

PMID- 27686339
TI  - A new approach to selective brain cooling by a Ranque-Hilsch vortex tube.
AB  - BACKGROUND: Target temperature management is the single most effective
      intervention and the gold standard in post-resuscitation care today. However,
      cooling the whole body below 33-34  degrees C can cause severe complications.
      Therefore, developing a selective brain cooling (SBC) approach which can be
      initiated early to induce rapid cooling and maintain the target temperature over
      12-24 h before slowly rewarming brain temperature by itself alone would be
      advantageous. Vortex tubes are simple mechanical devices generating cold air from
      a stream of compressed air without applied chemical or energy. This study
      investigated whether blowing cooled air from a vortex tube into the nasal
      cavities is safe and effective to selectively reduce and maintain before slowly
      rewarming brain temperature back to normal temperature. METHODS: Experiments were
      conducted on ten juvenile pigs. Body temperature was measured using an esophageal
      and a rectal temperature probe while brain temperature with an intraparenchymal
      thermocouple probe. Cerebral blood flow (CBF) was measured with CT perfusion.
      RESULTS: Brain temperature dropped below 34  degrees C within 30-40 min while a
      brain-esophageal temperature difference greater than 3  degrees C was maintained
      over 6 h. There was no evidence of nasal or nasopharynx mucosal swelling,
      necrosis, or hemorrhage on MRI examination. CBF first decreased and then
      stabilized together with brain temperature before increasing to the baseline
      level during rewarming. CONCLUSIONS: SBC was accomplished by blowing cold air
      from a vortex tube into the nasal cavities. Due to its portability, the method
      can be used continuously in resuscitated patients in both in- and out-of-hospital
      situations without interruption.

PMID- 27686340
TI  - Functional assessment for elimination of mismatches in nuclear and whole cell
      extracts obtained from mouse and human blastocysts.
AB  - Preimplantation embryos may have an increased risk of having mismatches due to
      the rates of cell proliferation and DNA replication. Elimination of mismatches in
      human gametes and embryos has not been investigated. In this study we developed a
      sensitive functional assay to examine the repair or elimination of mismatches in
      both commercially available cell extracts and extracts obtained from
      preimplantation embryos. Heteroduplex molecules were constructed using synthetic
      oligonucleotides. Efficiency of the repair of mismatches was semi-quantitatively
      analysed by exposure to nuclear/whole cell extracts (as little as 2.5 ug) and
      extracts obtained from pooled mouse and human blastocysts to investigate the
      repair capacity in human embryos. A cell free in vitro assay was successfully
      developed to analyze the repair of mismatches using heteroduplex complexes. The
      assay was further optimized to analyze repair of mismatches in cell extracts
      obtained from oocytes and blastocysts using minute amounts of protein. The
      efficiency of mismatch repair was examined in both mouse and human blastocysts
      (2.5 ug). The blastocysts were observed to have a lower repair efficiency
      compared to commercially available nuclear and whole cell extracts. In
      conclusion, a sensitive, easy, and fast in vitro technique was developed to
      detect the repair of mismatch efficiency in embryos.

PMID- 27686341
TI  - The Forgotten Virulence Factor: The 'non-conventional' Hemolysin TlyA And Its
      Role in Helicobacter pylori Infection.
AB  - Helicobacter pylori is a human-specific Gram-negative pathogenic bacterium which
      colonizes the gastric mucosal layer in the stomach causing diseases such as
      peptic ulcer, adenocarcinoma, and gastric lymphoma. It is estimated that
      approximately half of the world's population is infected with H. pylori making it
      the most intensively characterized microbial pathogen up to now. Hemolysis has
      been suggested to significantly contribute to colonization of the stomach and
      disease progression by H. pylori. In a number of earlier studies, TlyA was
      characterized as a putative pore-forming cytolysin. Although a few observations
      in the literature suggest a role for TlyA as significant virulence factor of H.
      pylori, the molecular and structural characterization of this protein is much
      curtailed at present. Given the intensive characterization of numerous H. pylori
      virulence factors over the past decade, surprisingly little information exists
      for the TlyA toxin and its significance for pathogenesis. This review provides a
      brief overview on microbial hemolysis and its role for pathogenesis and discusses
      recent research efforts aimed at an improved understanding of the role of the
      'non-conventional' hemolysin and its associated RNA methyltransferase TlyA from
      H. pylori.

PMID- 27686342
TI  - Total antioxidant status and lipid peroxidation with and without in vitro zinc
      supplementation in infertile men.
AB  - The aim of this study was to assess the total antioxidant capacity (TAC) and
      malondialdehyde (MDA) level in infertile men with asthenozoospermia and
      asthenoteratozoospermia compared to fertile donors, and to examine the effect of
      zinc on sperm lipid peroxidation and antioxidant status in infertile and fertile
      men. Semen samples provided by infertile men (n = 38) and fertile donors
      (controls; n = 12) were exposed to 6 mmol/L of zinc for 2 hr at 37 degrees C.
      After semen analysis, lipid peroxidation was detected by MDA assay and seminal
      TAC was assessed by colorimetric method using TAS (total antioxidant status) Kit.
      TAC was significantly lower in infertile group compared to controls (p = .037).
      However, lipid peroxidation did not alter in infertile patients compared to
      controls (p > .05). After in vitro incubation of samples with zinc, a significant
      increase in TAC level was found only in infertile men (p < .001). Meanwhile, zinc
      had no effect on sperm lipid peroxidation in both fertile and infertile men (p >
      .05). Our data indicate that antioxidant treatment based on zinc in vitro
      supplementation may be helpful to enhance the rate of seminal antioxidant status
      in infertile men; however, it does not prevent sperm lipid peroxidation.

PMID- 27686343
TI  - Nitric oxide administration during paediatric cardiopulmonary bypass: a
      randomised controlled trial.
AB  - PURPOSE: Cardiopulmonary bypass induces an ischaemia-reperfusion injury and
      systemic inflammatory response, which contributes to low cardiac output syndrome
      following cardiac surgery. Exogenous nitric oxide during cardiopulmonary bypass
      has shown potential to ameliorate such injury. We undertook a large randomised
      controlled trial to investigate the clinical effects of administering nitric
      oxide to the cardiopulmonary bypass circuit in children. METHODS: After written
      informed consent, children were randomised to receive 20 ppm nitric oxide to the
      gas inflow of the cardiopulmonary bypass oxygenator, or standard conduct of
      bypass. RESULTS: 101 children received nitric oxide and developed low cardiac
      output syndrome less frequently (15 vs. 31 %, p = 0.007) than the 97 children who
      did not receive nitric oxide. This effect was most marked in children aged less
      than 6 weeks of age (20 vs. 52 %, p = 0.012) and in those aged 6 weeks to 2 years
      (6 vs. 24 %, p = 0.026), who also had significantly reduced ICU length of stay
      (43 vs. 84 h, p = 0.031). Low cardiac output syndrome was less frequent following
      more complex surgeries if nitric oxide was administered (17 vs. 48 %, p = 0.018).
      ECMO was used less often in the nitric oxide group (1 vs. 8 %, p = 0.014).
      CONCLUSIONS: Delivery of nitric oxide to the oxygenator gas flow during
      paediatric cardiopulmonary bypass reduced the incidence of low cardiac output
      syndrome by varying degrees, according to age group and surgery complexity.
      CLINICAL TRIAL REGISTRATION: ACTRN12615001376538.

PMID- 27686344
TI  - No harm, no benefit: should we give up with neurally adjusted ventilatory assist?

PMID- 27686345
TI  - Long-term outcomes in patients with septic shock transfused at a lower versus a
      higher haemoglobin threshold: the TRISS randomised, multicentre clinical trial.
AB  - PURPOSE: We assessed the predefined long-term outcomes in patients randomised in
      the Transfusion Requirements in Septic Shock (TRISS) trial. METHODS: In 32
      Scandinavian ICUs, we randomised 1005 patients with septic shock and haemoglobin
      of 9 g/dl or less to receive single units of leuko-reduced red cells when
      haemoglobin level was 7 g/dl or less (lower threshold) or 9 g/dl or less (higher
      threshold) during ICU stay. We assessed mortality rates 1 year after
      randomisation and again in all patients at time of longest follow-up in the
      intention-to-treat population (n = 998) and health-related quality of life
      (HRQoL) 1 year after randomisation in the Danish patients only (n = 777).
      RESULTS: Mortality rates in the lower- versus higher-threshold group at 1 year
      were 53.5 % (268/501 patients) versus 54.6 % (271/496) [relative risk 0.97; 95 %
      confidence interval (CI) 0.85-1.09; P = 0.62]; at longest follow-up (median 21
      months), they were 56.7 % (284/501) versus 61.0 % (302/495) (hazard ratio 0.88;
      95 % CI 0.75-1.03; P = 0.12). We obtained HRQoL data at 1 year in 629 of the 777
      (81 %) Danish patients, and mean differences between the lower- and higher
      threshold group in scores of physical HRQoL were 0.4 (95 % CI -2.4 to 3.1; P =
      0.79) and in mental HRQoL 0.5 (95 % CI -3.1 to 4.0; P = 0.79). CONCLUSIONS: Long
      term mortality rates and HRQoL did not differ in patients with septic shock and
      anaemia who were transfused at a haemoglobin threshold of 7 g/dl versus a
      threshold of 9 g/dl. We may reject a more than 3 % increased hazard of death in
      the lower- versus higher-threshold group at the time of longest follow-up.

PMID- 27686346
TI  - Intravenous iron or placebo for anaemia in intensive care: the IRONMAN
      multicentre randomized blinded trial : A randomized trial of IV iron in critical
      illness.
AB  - PURPOSE: Both anaemia and allogenic red blood cell transfusion are common and
      potentially harmful in patients admitted to the intensive care unit. Whilst
      intravenous iron may decrease anaemia and RBC transfusion requirement, the safety
      and efficacy of administering iron intravenously to critically ill patients is
      uncertain. METHODS: The multicentre, randomized, placebo-controlled, blinded
      Intravenous Iron or Placebo for Anaemia in Intensive Care (IRONMAN) study was
      designed to test the hypothesis that, in anaemic critically ill patients admitted
      to the intensive care unit, early administration of intravenous iron, compared
      with placebo, reduces allogeneic red blood cell transfusion during hospital stay
      and increases the haemoglobin level at the time of hospital discharge. RESULTS:
      Of 140 patients enrolled, 70 were assigned to intravenous iron and 70 to placebo.
      The iron group received 97 red blood cell units versus 136 red blood cell units
      in the placebo group, yielding an incidence rate ratio of 0.71 [95 % confidence
      interval (0.43-1.18), P = 0.19]. Overall, median haemoglobin at hospital
      discharge was significantly higher in the intravenous iron group than in the
      placebo group [107 (interquartile ratio IQR 97-115) vs. 100 g/L (IQR 89-111), P =
      0.02]. There was no significant difference between the groups in any safety
      outcome. CONCLUSIONS: In patients admitted to the intensive care unit who were
      anaemic, intravenous iron, compared with placebo, did not result in a significant
      lowering of red blood cell transfusion requirement during hospital stay. Patients
      who received intravenous iron had a significantly higher haemoglobin
      concentration at hospital discharge. The trial was registered at
      http://www.anzctr.org.au as # ACTRN12612001249842.

PMID- 27686347
TI  - Neurally adjusted ventilatory assist as an alternative to pressure support
      ventilation in adults: a French multicentre randomized trial.
AB  - PURPOSE: Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that
      tailors the level of assistance delivered by the ventilator to the
      electromyographic activity of the diaphragm. The objective of this study was to
      compare NAVA and pressure support ventilation (PSV) in the early phase of weaning
      from mechanical ventilation. METHODS: A multicentre randomized controlled trial
      of 128 intubated adults recovering from acute respiratory failure was conducted
      in 11 intensive care units. Patients were randomly assigned to NAVA or PSV. The
      primary outcome was the probability of remaining in a partial ventilatory mode
      (either NAVA or PSV) throughout the first 48 h without any return to assist
      control ventilation. Secondary outcomes included asynchrony index, ventilator
      free days and mortality. RESULTS: In the NAVA and PSV groups respectively, the
      proportion of patients remaining in partial ventilatory mode throughout the first
      48 h was 67.2 vs. 63.3 % (P = 0.66), the asynchrony index was 14.7 vs. 26.7 % (P
      < 0.001), the ventilator-free days at day 7 were 1.0 day [1.0-4.0] vs. 0.0 days
      [0.0-1.0] (P < 0.01), the ventilator-free days at day 28 were 21 days [4-25] vs.
      17 days [0-23] (P = 0.12), the day-28 mortality rate was 15.0 vs. 22.7 % (P =
      0.21) and the rate of use of post-extubation noninvasive mechanical ventilation
      was 43.5 vs. 66.6 % (P < 0.01). CONCLUSIONS: NAVA is safe and feasible over a
      prolonged period of time but does not increase the probability of remaining in a
      partial ventilatory mode. However, NAVA decreases patient-ventilator asynchrony
      and is associated with less frequent application of post-extubation noninvasive
      mechanical ventilation. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT02018666.

PMID- 27686348
TI  - Getting down to the real question: effects of transfusion triggers on long-term
      survival and quality of life following septic shock.

PMID- 27686350
TI  - Improving outcomes after critical illness: harder than we thought!

PMID- 27686349
TI  - Restricting volumes of resuscitation fluid in adults with septic shock after
      initial management: the CLASSIC randomised, parallel-group, multicentre
      feasibility trial.
AB  - PURPOSE: We assessed the effects of a protocol restricting resuscitation fluid
      vs. a standard care protocol after initial resuscitation in intensive care unit
      (ICU) patients with septic shock. METHODS: We randomised 151 adult patients with
      septic shock who had received initial fluid resuscitation in nine Scandinavian
      ICUs. In the fluid restriction group fluid boluses were permitted only if signs
      of severe hypoperfusion occurred, while in the standard care group fluid boluses
      were permitted as long as circulation continued to improve. RESULTS: The co
      primary outcome measures, resuscitation fluid volumes at day 5 and during ICU
      stay, were lower in the fluid restriction group than in the standard care group
      [mean differences -1.2 L (95 % confidence interval -2.0 to -0.4); p < 0.001 and 
      1.4 L (-2.4 to -0.4) respectively; p < 0.001]. Neither total fluid inputs and
      balances nor serious adverse reactions differed statistically significantly
      between the groups. Major protocol violations occurred in 27/75 patients in the
      fluid restriction group. Ischaemic events occurred in 3/75 in the fluid
      restriction group vs. 9/76 in the standard care group (odds ratio 0.32; 0.08
      1.27; p = 0.11), worsening of acute kidney injury in 27/73 vs. 39/72 (0.46; 0.23
      0.92; p = 0.03), and death by 90 days in 25/75 vs. 31/76 (0.71; 0.36-1.40; p =
      0.32). CONCLUSIONS: A protocol restricting resuscitation fluid successfully
      reduced volumes of resuscitation fluid compared with a standard care protocol in
      adult ICU patients with septic shock. The patient-centred outcomes all pointed
      towards benefit with fluid restriction, but our trial was not powered to show
      differences in these exploratory outcomes. TRIAL REGISTRATION: NCT02079402.

PMID- 27686351
TI  - Improvement in functional abilities at ICU discharge is feasible without
      prolongation of the length of stay ICU.

PMID- 27686352
TI  - The effects of performance status one week before hospital admission on the
      outcomes of critically ill patients.
AB  - PURPOSE: To assess the impact of performance status (PS) impairment 1 week before
      hospital admission on the outcomes in patients admitted to intensive care units
      (ICU). METHODS: Retrospective cohort study in 59,693 patients (medical
      admissions, 67 %) admitted to 78 ICUs during 2013. We classified PS impairment
      according to the Eastern Cooperative Oncology Group (ECOG) scale in absent/minor
      (PS = 0-1), moderate (PS = 2) or severe (PS = 3-4). We used univariate and
      multivariate logistic regression analyses to investigate the association between
      PS impairment and hospital mortality. RESULTS: PS impairment was moderate in 17.3
      % and severe in 6.9 % of patients. The hospital mortality was 14.4 %. Overall,
      the worse the PS, the higher the ICU and hospital mortality and length of stay.
      In addition, patients with worse PS were less frequently discharged home. PS
      impairment was associated with worse outcomes in all SAPS 3, Charlson Comorbidity
      Index and age quartiles as well as according to the admission type. Adjusting for
      other relevant clinical characteristics, PS impairment was associated with higher
      hospital mortality (odds-ratio (OR) = 1.96 (95 % CI 1.63-2.35), for moderate and
      OR = 4.22 (3.32-5.35), for severe impairment). The effects of PS on the outcome
      were particularly relevant in the medium range of severity-of-illness. These
      results were consistent in the subgroup analyses. However, adding PS impairment
      to the SAPS 3 score improved only slightly its discriminative capability.
      CONCLUSION: PS impairment was associated with worse outcomes independently of
      other markers of chronic health status, particularly for patients in the medium
      range of severity of illness.

PMID- 27686354
TI  - Prone position and VAP incidence in the PROSEVA trial: attention to the causal
      question when interpreting competing risk analysis.

PMID- 27686353
TI  - The optimal target for acute glycemic control in critically ill patients: a
      network meta-analysis.
AB  - PURPOSE: The optimal target blood glucose concentration for acute glycemic
      control remains unclear because few studies have directly compared 144-180 with
      110-144 or >180 mg/dL. Accordingly, we performed a network meta-analysis to
      compare four different target blood glucose levels (<110, 110-144, 144-180, and
      >180 mg/dL) in terms of the benefit and risk of insulin therapy. METHODS: We
      included all of the studies from three systematic reviews and searched the PubMed
      and Cochrane databases for other studies investigating glucose targets among
      critically ill patients. The primary outcome was hospital mortality, and the
      secondary outcomes were sepsis or bloodstream infection and the risk of
      hypoglycemia. Network meta-analysis to identify an optimal target glucose
      concentration. RESULTS: The network meta-analysis included 18,098 patients from
      35 studies. There were no significant differences in the risk of mortality and
      infection among the four blood glucose ranges overall or in subgroup analysis.
      Conversely, target concentrations of <110 and 110-144 mg/dL were associated with
      a four to ninefold increase in the risk of hypoglycemia compared with 144-180 and
      >180 mg/dL. However, there were no significant differences between the target
      concentrations of 144-180 and >180 mg/dL. CONCLUSIONS: This network meta-analysis
      found no significant difference in the risk of mortality and infection among four
      target blood glucose ranges in critically ill patients, but indicated that target
      blood glucose levels of <110 and 110-144 mg/dL were associated with a higher risk
      of hypoglycemia than target levels of 144-180 and >180 mg/dL. Further studies are
      required to refute or confirm our findings.

PMID- 27686355
TI  - Incidence of severe sepsis and septic shock in German intensive care units: the
      prospective, multicentre INSEP study.
AB  - PURPOSE: To estimate the incidence density, point prevalence and outcome of
      severe sepsis and septic shock in German intensive care units (ICUs). METHODS: In
      a prospective, multicentre, longitudinal observational study, all patients
      already on the ICU at 0:00 on 4 November 2013 and all patients admitted to a
      participating ICU between 0:00 on 4 November 2013 and 2359 hours on 1 December
      2013 were included. The patients were followed up for the occurrence of severe
      sepsis or septic shock (SEPSIS-1 definitions) during their ICU stay. RESULTS: A
      total of 11,883 patients from 133 ICUs at 95 German hospitals were included in
      the study, of whom 1503 (12.6 %) were diagnosed with severe sepsis or septic
      shock. In 860 cases (57.2 %) the infections were of nosocomial origin. The point
      prevalence was 17.9 % (95 % CI 16.3-19.7).The calculated incidence rate of severe
      sepsis or septic shock was 11.64 (95 % CI 10.51-12.86) per 1000 ICU days. ICU
      mortality in patients with severe sepsis/septic shock was 34.3 %, compared with 6
      % in those without sepsis. Total hospital mortality of patients with severe
      sepsis or septic shock was 40.4 %. Classification of the septic shock patients
      using the new SEPSIS-3 definitions showed higher ICU and hospital mortality (44.3
      and 50.9 %). CONCLUSIONS: Severe sepsis and septic shock continue to be a
      frequent syndrome associated with high hospital mortality. Nosocomial infections
      play a major role in the development of sepsis. This study presents a pragmatic,
      affordable and feasible method for the surveillance of sepsis epidemiology.
      Implementation of the new SEPSIS-3 definitions may have a major effect on future
      epidemiological data.

PMID- 27686356
TI  - Prone position and VAP incidence in the PROSEVA trial: attention to the causal
      question when interpreting competing risk analysis-response to comments by
      Ranzani et al.

PMID- 27686357
TI  - In sepsis, everything old is new again.

PMID- 27686358
TI  - Focus on adequate antimicrobial treatment and de-escalation in the ICU.

PMID- 27686359
TI  - Vertebral erosion: a rare complication of tracheostomy tube.

PMID- 27686360
TI  - Comparison of conventional and ultrasound guided techniques of radial artery
      cannulation in different haemodynamic subsets: a randomised controlled study.

PMID- 27686362
TI  - Quality of life after brain injury (QOLIBRI): Italian validation of the proxy
      version.
AB  - To validate the proxy version of the Quality of Life after Brain Injury (QOLIBRI)
      questionnaire to utilize caregivers for comparison and to evaluate the
      correspondence between patients' self-perceived and caregivers' perception of
      patients' Health-Related Quality of Life (HRQoL). Ninety-two patients with severe
      TBI and their main caregivers were enrolled. Patients' and caregivers' HRQoL was
      assessed by the Patient-QOLIBRI (Pt-QOLIBRI) and the Proxy-QOLIBRI (Pro-QOLIBRI),
      respectively. The Pro-QOLIBRI is a modified version of the QOLIBRI to investigate
      caregivers' perception of patients' HRQoL (Pro-QOLIBRIpatient-centered), and
      their degree of satisfaction and botheredness (Pro-QOLIBRIcaregiver centered).
      The patients' disability and their social reintegration was investigated by means
      of Glasgow Outcome Scale Extended and Community Integration Questionnaire. Pro
      QOLIBRI has good internal consistency and homogeneity. There was also positive
      correlation between the level of satisfaction measured by Pro-QOLIBRI but not by
      Pt-QOLIBRI, and the disability severity and social integration of the patients.
      The comparison between the Pt-QOLIBRI and Pro-QOLIBRI confirmed the usefulness of
      the Pro-QOLIBRI, especially the caregiver-centered version, to predict the social
      reintegration of survivors. To our knowledge this is the first study that
      correlates the HRQoL of survivors, as self-perceived and as perceived by the
      caregivers with social reintegration.

PMID- 27686363
TI  - Is Hepatitis Delta infections important in Brazil?
AB  - BACKGROUND: The Hepatitis Delta Virus (HDV) can increase the incidence of
      fulminant hepatitis. For this infection occurs, the host must also be infected
      with Hepatitis B Virus. Previous studies demonstrated the endemicity and near
      exclusivity of this infection in the Amazon region, and as a consequence of the
      difficulty in accessing this area we used dried blood spots (DBS) in sample
      collection. The aims of this study were to investigate the presence of
      recombination, to analyze the epidemiology, ancestry and evolutionary pressures
      on HDV in Brazil. METHODS: Blood samples from 50 individuals were collected using
      dried-blood spots (DBS 903, Whatman), and sent via regular mail to Retrovirology
      Laboratory from Federal University of Sao Paulo, where the samples were
      processed. In the analysis the following software were used: PhyML, RDP, BEAST,
      jModelTest and CODEML. RESULTS: Our results confirm the prevalence of HDV-3 in
      the Amazon region of Brazil, with the absence of inter-genotypic recombination.
      It was identified a positive selection in probable epitopes of HDV on B
      lymphocytes that might indicate that the virus is changing to escape the humoral
      response of the host. The analysis of the time of the most common ancestor
      demonstrated the exponential growth of this virus in late 1970s that lasted until
      1995, after which it remained constant. It was also observed a probable founder
      effect in two cities, which demonstrate the need to focus on prevention methods
      against HBV/HDV infection. CONCLUSION: We confirmed the prevalence of HDV-3 in
      the Amazon region of Brazil, without inter-genotypic recombination. The analysis
      of the time of the most common ancestor showed that this infection remain
      constant in the studied area. Taking into account the probable founder effect
      established in the cities of Rio Branco and Porto Velho, a focus on preventive
      methods is recommended against these infections.

PMID- 27686364
TI  - Charcot-Marie-Tooth disease type 2G redefined by a novel mutation in LRSAM1.
AB  - OBJECTIVE: To identify the unknown genetic cause in a large pedigree previously
      classified with a distinct form of axonal Charcot-Marie-Tooth disease type 2G
      (CMT2G) and to explore its transcriptional consequences. METHODS: Clinical
      reevaluation of the pedigree was performed, followed by linkage analysis with the
      redefined disease statuses, and whole genome and exome sequencing. The impact of
      the mutation was investigated by immunoblotting and transcriptome sequencing.
      RESULTS: Thirteen affected individuals over 3 generations displayed mild and
      quiescent lower-limb axonal sensorimotor neuropathy. Magnetic resonance imaging
      (MRI) of lower-limb musculature systematically showed fatty atrophy in clinical
      and subclinical mutation carriers. We redefined the disease-linked region to
      chr9q31.3-q34.2 and subsequently identified a novel missense variant in the E3
      ubiquitin-protein ligase LRSAM1 (p.Cys694Tyr). Unlike previous reports, we
      demonstrated in patients' lymphoblasts that the mutation does not influence
      overall protein levels of LRSAM1, nor of its ubiquitylation target TSG101. The
      mutation is associated with several transcriptional changes, including a
      significant upregulation of another E3 ubiquitin-protein ligase, NEDD4L, and of
      TNFRSF21, a key regulator of axonal degeneration. INTERPRETATION: Our findings
      demonstrate that the isolated genetic entity CMT2G is caused by a missense
      mutation in LRSAM1 and should be reclassified as CMT2P. MRI of lower-limb
      musculature can be used to detect minimal signs of the disease. Transcriptome
      analysis of patients' cells highlights novel molecular players associated with
      LRSAM1 dysfunction, and reveals pathways and therapeutic targets shared with
      amyotrophic lateral sclerosis and Alzheimer disease. Ann Neurol 2016;80:823-833.

PMID- 27686366
TI  - Metformin-related lactic acidosis: is it a myth or an underestimated reality?
AB  - Metformin, belonging to a class of drugs called biguanides, is the recommended
      first-line treatment for overweight patients with type 2 diabetes mellitus. It
      has multiple mechanisms of action, such as reduction of gluconeogenesis,
      increases peripheral uptake of glucose, and decreases fatty acid oxidation.
      However, a potential serious complication, defined metformin-associated lactic
      acidosis (MALA), is related to increased plasma lactate levels, linked to an
      elevated plasma metformin concentrations and/or a coexistent condition altering
      lactate production or clearance. The mortality rate for MALA approaches 50% and
      metformin has been contraindicated in moderate and severe renal impairment, to
      minimize its potential toxic levels. Nevertheless, metformin prescription or
      administration, despite the presence of contraindications or precipitating
      factors for MALA, was a common topic highlighted in all reviewed papers. Routine
      assessment of metformin plasma concentration is not easily available in all
      laboratories, but plasma metformin concentrations measured in the emergency room
      could ensure the correct diagnosis, eliminating metformin as the cause of lactic
      acidosis if low plasma levels occurred. Renal replacement therapies have been
      successfully employed to achieve the correction of metabolic acidosis and rapidly
      remove metformin and lactate, but the optimal treatment modality for MALA is
      still controversial.

PMID- 27686365
TI  - Randomized clinical trial of observational versus antibiotic treatment for a
      first episode of CT-proven uncomplicated acute diverticulitis.
AB  - BACKGROUND: Antibiotics are advised in most guidelines on acute diverticulitis,
      despite a lack of evidence to support their routine use. This trial compared the
      effectiveness of a strategy with or without antibiotics for a first episode of
      uncomplicated acute diverticulitis. METHODS: Patients with CT-proven, primary,
      left-sided, uncomplicated, acute diverticulitis were included at 22 clinical
      sites in the Netherlands, and assigned randomly to an observational or antibiotic
      treatment strategy. The primary endpoint was time to recovery during 6 months of
      follow-up. Main secondary endpoints were readmission rate, complicated, ongoing
      and recurrent diverticulitis, sigmoid resection and mortality. Intention-to-treat
      and per-protocol analyses were done. RESULTS: A total of 528 patients were
      included. Median time to recovery was 14 (i.q.r. 6-35) days for the observational
      and 12 (7-30) days for the antibiotic treatment strategy, with a hazard ratio for
      recovery of 0.91 (lower limit of 1-sided 95 per cent c.i. 0.78; P = 0.151). No
      significant differences between the observation and antibiotic treatment groups
      were found for secondary endpoints: complicated diverticulitis (3.8 versus 2.6
      per cent respectively; P = 0.377), ongoing diverticulitis (7.3 versus 4.1 per
      cent; P = 0.183), recurrent diverticulitis (3.4 versus 3.0 per cent; P = 0.494),
      sigmoid resection (3.8 versus 2.3 per cent; P = 0.323), readmission (17.6 versus
      12.0 per cent; P = 0.148), adverse events (48.5 versus 54.5 per cent; P = 0.221)
      and mortality (1.1 versus 0.4 per cent; P = 0.432). Hospital stay was
      significantly shorter in the observation group (2 versus 3 days; P = 0.006). Per
      protocol analyses were concordant with the intention-to-treat analyses.
      CONCLUSION: Observational treatment without antibiotics did not prolong recovery
      and can be considered appropriate in patients with uncomplicated diverticulitis.
      Registration number: NCT01111253 (http://www.clinicaltrials.gov).

PMID- 27686367
TI  - Setting the scene for the future: implications of key legal regulations for the
      development of e-health interoperability in the EU.
AB  - E-health has experienced a dynamic development across the European Union in the
      recent years and enjoys support from the European Commission that seeks to
      achieve interoperability of national healthcare systems in order to facilitate
      free movement. Differences that can be observed between the member states in
      legal regulations, cultural approaches and technological solutions may hinder
      this process. This study compares the legal standing of e-health in Denmark,
      Poland, Spain and the UK, along with key legal acts and their implications. The
      academic literature review along with an analysis of materials found through the
      desk study research (reports, legal acts, press articles, governmental web pages
      and so on) was performed in order to identify aspects relevant to e-health
      interoperability. The approach to legal regulation of e-health substantially
      differs by country. So do the procedures that they have developed regarding the
      requirement for patient's consent for the processing of their data, their rights
      to access to the medical data, to change the data, data confidentiality and types
      of electronic health records. The principles governing the assignment of
      responsibility for data protection are also different. These legal and
      technological differences must be reconciled if interoperability of European
      national e-health systems is to be achieved. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27686368
TI  - Classification and regression tree analysis of acute-on-chronic hepatitis B liver
      failure: Seeing the forest for the trees.
AB  - At present, there is no ideal model for predicting the short-term outcome of
      patients with acute-on-chronic hepatitis B liver failure (ACHBLF). This study
      aimed to establish and validate a prognostic model by using the classification
      and regression tree (CART) analysis. A total of 1047 patients from two separate
      medical centres with suspected ACHBLF were screened in the study, which were
      recognized as derivation cohort and validation cohort, respectively. CART
      analysis was applied to predict the 3-month mortality of patients with ACHBLF.
      The accuracy of the CART model was tested using the area under the receiver
      operating characteristic curve, which was compared with the model for end-stage
      liver disease (MELD) score and a new logistic regression model. CART analysis
      identified four variables as prognostic factors of ACHBLF: total bilirubin, age,
      serum sodium and INR, and three distinct risk groups: low risk (4.2%),
      intermediate risk (30.2%-53.2%) and high risk (81.4%-96.9%). The new logistic
      regression model was constructed with four independent factors, including age,
      total bilirubin, serum sodium and prothrombin activity by multivariate logistic
      regression analysis. The performances of the CART model (0.896), similar to the
      logistic regression model (0.914, P=.382), exceeded that of MELD score (0.667,
      P<.001). The results were confirmed in the validation cohort. We have developed
      and validated a novel CART model superior to MELD for predicting three-month
      mortality of patients with ACHBLF. Thus, the CART model could facilitate medical
      decision-making and provide clinicians with a validated practical bedside tool
      for ACHBLF risk stratification.

PMID- 27686369
TI  - Analysis of the characteristics of persistent postural-perceptual dizziness: A
      clinical-based study in China.
AB  - OBJECTIVE: Persistent postural-perceptual dizziness (PPPD) is a common cause of
      chronic dizziness, but only a few studies have reported its clinical
      characteristics, and no related research has been performed in China. Therefore,
      the purpose of this study was to analyze the characteristics of PPPD for the
      first time in China. DESIGN: Data was collected from all patients during standard
      clinical practice, and further to evaluate the characteristics of PPPD comparing
      with the control group. STUDY SAMPLE: A total of 43 patients diagnosed with PPPD
      were selected as the study group for analysis. RESULTS: Women were significantly
      more represented in the study group than men, and in the majority of cases the
      age of onset was in middle-age, and sleep quality was clearly decreased compared
      with controls, with more statistically significantly higher levels of anxiety.
      Personality analysis identified that neuroticism was significantly higher than in
      controls. CONCLUSIONS: In this sample we showed that PPPD was more represented in
      female patients, the age of onset was 40-60 years old, the majority of patients
      had sleep disorders, anxiety was the main mood disorder to be identified, and
      personality analysis found that neurotic personality may be the risk factor for
      developing PPPD. Further large scale studies are suggested in China.

PMID- 27686370
TI  - Nutritional status and complementary feeding among HIV-exposed infants: a
      prospective cohort study.
AB  - Complementary feeding is crucial for improving child survival and promoting
      growth and development, particularly among HIV-exposed children who have higher
      risk of morbidity and mortality than their un-exposed peers. This prospective
      study employed an infant and child feeding index (ICFI) to measure complementary
      feeding and determine its association with nutritional status among 2092 HIV
      exposed infants followed from 6 to 24 months of age in Dar es Salaam, Tanzania.
      The ICFI measured both quality and quantity of complementary feeding, including
      current breastfeeding status, food consistency, dietary diversity scores (DDS),
      food group frequency score, and meal frequency. The ICFI score ranged from 0 to
      9; the median score was 6 (Inter-Quartile Range, IQR= 4-7). After adjusting for
      potential confounders, high ICFI scores were associated with reduced risk of
      stunting (high vs. low tertile hazard ratio, HR: 0.72; 95% confidence interval,
      CI: 0.57, 0.91; P< 0.01) and underweight (high vs. low tertile HR: 0.79; 95% CI:
      0.61, 1.02; P= 0.07). Low DDS were associated with higher risk of stunting (low
      vs. high tertile HR: 1.59; 95% CI: 1.23, 2.07; P< 0.01) and underweight (low vs.
      high tertile HR: 1.48; 95% CI: 1.12, 1.96; P= 0.01). In this setting, high DDS
      and ICFI scores were protective of stunting and underweight. We recommend for
      nutrition programs in low-income countries to emphasize educating HIV-exposed
      children's caregivers on the importance of dietary diversity and optimal
      complementary feeding to improve nutritional status in this important
      subpopulation.

PMID- 27686371
TI  - To image or not to image? A cost-effectiveness analysis of MRI for patients with
      asymmetric sensorineural hearing loss.
AB  - OBJECTIVES/HYPOTHESIS: Our objective was to perform an economic analysis
      evaluating whether ordering a magnetic resonance imaging (MRI) is a cost
      effective practice in the workup of undifferentiated asymmetric sensorineural
      hearing loss (ASNHL). Use of T1 gadolinium-weighted MR (GdT1W) and T2 weighted MR
      without contrast (T2MR) was each examined. METHODS: The incremental cost
      effectiveness ratio (ICER) of MR imaging among ASNHL patients was evaluated using
      a decision tree. We calculated what the probability of having a cerebellopontine
      angle/internal auditory canal lesion would have to be to make MR more cost
      effective than observation. The decision pathways included observation, GdT1W,
      and T2MR. The probability of detecting a lesion and associated costs were
      employed in constructing our tree. Missing a mass in the observation branch was
      considered to have an effectiveness of 0. The costs and probabilities were
      extracted from previously published studies. RESULTS: The ICERs of pursuing GdT1W
      and T2MR were $27,660 and $15,943, respectively, both below the widely accepted
      willingness to pay (WTP) thresholds of $30,000 and $50,000. Probabilistic
      sensitivity analysis with Monte Carlo simulations for GdT1W showed that it is
      more cost-effective than no imaging, with 54.4% and 83.5% certainty at $30,000
      and $50,000 WTP thresholds. Probabilistic sensitivity analysis with Monte Carlo
      simulations for T2MR showed that it is more cost-effective than no imaging, with
      75.2% and 92.6% certainty at $30,000 and $50,000 WTP thresholds. CONCLUSION: This
      economic evaluation strongly supports pursuing MRI in patients with documented
      ASNHL as a cost-effective strategy. Both GdT1W and T2MR are more cost-effective
      than observation. Furthermore, noncontrast T2 imaging may be the more cost
      effective modality of these two techniques. LEVEL OF EVIDENCE: 2c. Laryngoscope,
      127:939-944, 2017.

PMID- 27686372
TI  - Interleukin-15 enhances the proliferation, stimulatory phenotype, and antitumor
      effector functions of human gamma delta T cells.
AB  - BACKGROUND: Adoptive immunotherapy is gaining momentum to fight malignancies,
      whereby gammadelta T cells have received recent attention as an alternative cell
      source as to natural killer cells and alphabeta T cells. The advent of gammadelta
      T cells is largely due to their ability to recognize and target tumor cells using
      both innate characteristic and T cell receptor (TCR)-mediated mechanisms, their
      capacity to enhance the generation of antigen-specific T cell responses, and
      their potential to be used in an autologous or allogeneic setting. METHODS: In
      this study, we explored the beneficial effect of the immunostimulatory cytokine
      interleukin (IL)-15 on purified gammadelta T cells and its use as a stimulatory
      signal in the ex vivo expansion of gammadelta T cells for adoptive transfer. The
      expansion protocol was validated both with immune cells of healthy individuals
      and acute myeloid leukemia patients. RESULTS: We report that the addition of IL
      15 to gammadelta T cell cultures results in a more activated phenotype, a higher
      proliferative capacity, a more pronounced T helper 1 polarization, and an
      increased cytotoxic capacity of gammadelta T cells. Moreover gammadelta T cell
      expansion starting with peripheral blood mononuclear cells from healthy
      individuals and acute myeloid leukemia patients is boosted in the presence of IL
      15, whereby the antitumor properties of the gammadelta T cells are strengthened
      as well. CONCLUSIONS: Our results support the rationale to explore the use of IL
      15 in clinical adoptive therapy protocols exploiting gammadelta T cells.

PMID- 27686373
TI  - Regenerate bone stimulation following limb lengthening: a meta-analysis.
AB  - BACKGROUND: Limb lengthening with external fixation is performed to treat
      patients with leg length discrepancy or short stature. Although the procedure has
      a high rate of success, one potential drawback from limb lengthening is the
      amount of time spent in the fixation device while regenerate bone consolidates.
      Although some studies have assessed different treatment modalities, there has not
      been a study that has systematically evaluated whether low intensity pulsed
      ultrasound (LIPUS) or pulsed electromagnetic fields (PEMF) have significant
      effects on regenerate bone growth. The purpose of this study was to evaluate
      these two non-pharmacological treatment options to stimulate regenerate bone, and
      to assess whether they affect the treatment time in limb lengthening. METHODS:
      Utilizing the electronic databases Medline, Embase and Ovid, we performed a
      literature search for studies describing the application of LIPUS or PEMF
      following limb lengthening. With the aid of a statistical software package,
      Forest-Plots were generated to compare the differences in bone healing index with
      and without the use of regenerate bone stimulation. RESULTS: A total of 7 studies
      assessed these two bone stimulation modalities in a cohort of 153 patients.
      Overall, the mean healing index was 11.7 days/cm faster when using bone
      stimulation that in the comparison cohorts (33.7 vs 45.4 day, standardized mean
      difference of 1.16; p = 0.003). CONCLUSION: Amongst the drawbacks from limb
      lengthening is the relatively high rate of non- and delayed-union. Several
      methods, both pharmacological and non-pharmacological, have been investigated for
      their potential to stimulate the growth of regenerate bone. After systematically
      evaluating the limited and heterogeneous current literature, we found that LIPUS
      and PEMF both decreased the time for bone healing (healing index in days/cm) of
      the newly formed regenerate bone in an adequately selected cohort of patients
      that underwent limb lengthening. However, a high number of complications should
      be noted, which could be attributed to the lengthening procedure or to the
      additional bone stimulation. PROSPERO REGISTRATION NUMBER: CRD42016039024.

PMID- 27686374
TI  - Impaired pulmonary endothelial barrier function in sickle cell mice.

PMID- 27686375
TI  - The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the
      central nervous system.
AB  - Central nervous system infiltration and relapse are poorly understood in
      childhood acute lymphoblastic leukemia. We examined the role of zeta-chain
      associated protein kinase 70 in preclinical models of central nervous system
      leukemia and performed correlative studies in patients. Zeta-chain-associated
      protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated
      using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We
      show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via
      activation of extracellular signal-regulated kinases. High expression of zeta
      chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted
      in a higher proportion of central nervous system leukemia in xenografts as
      compared to zeta-chain-associated protein kinase 70 low expressing counterparts.
      High zeta-chain-associated protein kinase 70 also enhanced the migration
      potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated
      homing of acute lymphoblastic leukemia cells to the central nervous system in
      xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell
      acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70
      and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain
      associated protein kinase 70 expression correlated with central nervous system
      disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4
      correlated with central nervous system involvement in T-cell acute lymphoblastic
      leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase
      70 expression levels in the upper third and fourth quartiles were associated with
      central nervous system involvement in B-cell precursor acute lymphoblastic
      leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86,
      95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper
      fourth quartile correlated with central nervous system positivity in T-cell acute
      lymphoblastic leukemia (odds ratio=11.00, 95% confidence interval, 2.00-60.62).
      We propose zeta-chain-associated protein kinase 70, CCR7 and CXCR4 as markers of
      central nervous system infiltration in acute lymphoblastic leukemia warranting
      prospective investigation.

PMID- 27686376
TI  - Improving results of allogeneic hematopoietic cell transplantation for adults
      with acute lymphoblastic leukemia in first complete remission: an analysis from
      the Acute Leukemia Working Party of the European Society for Blood and Marrow
      Transplantation.
AB  - Allogeneic hematopoietic cell transplantation is widely used to treat adults with
      high-risk acute lymphoblastic leukemia. The aim of this study was to analyze
      whether the results changed over time and to identify prognostic factors. Adult
      patients treated between 1993 and 2012 with myeloablative allogeneic
      hematopoietic cell transplantation from HLA matched sibling (n=2681) or unrelated
      (n=2178) donors in first complete remission were included. For transplantations
      from sibling donors performed between 2008 and 2012, 2-year probabilities of
      overall survival were: 76% (18-25 years old), 69% (26-35 and 36-45 years old) and
      60% (46-55 years old). Among recipients of transplantations from unrelated
      donors, the respective survival rates were 66%, 70%, 61%, and 62%. In comparison
      with the 1993-2007 period, significant improvements were observed for all age
      groups except for the 26-35-year old patients. In a multivariate model,
      transplantations performed between 2008 and 2012, when compared to 1993-2007,
      were associated with significantly reduced risks of non-relapse mortality (Hazard
      Ratio 0.77, P=0.00006), relapse (Hazard Ratio 0.85, P=0.007), treatment failure
      (Hazard Ratio 0.81, P<0.00001), and overall mortality (Hazard Ratio 0.79,
      P<0.00001). In the analysis restricted to transplantations performed between 2008
      and 2012, the use of total body irradiation-based conditioning was associated
      with reduced risk of relapse (Hazard Ratio 0.48, P=0.004) and treatment failure
      (Hazard Ratio 0.63, P=0.02). We conclude that results of allogeneic hematopoietic
      cell transplantation for adults with acute lymphoblastic leukemia improved
      significantly over time. Total body irradiation should be considered as the
      preferable type of myeloablative conditioning.

PMID- 27686377
TI  - Risk of thrombosis according to need of phlebotomies in patients with
      polycythemia vera treated with hydroxyurea.
AB  - Hematocrit control below 45% is associated with a lower rate of thrombosis in
      polycythemia vera. In patients receiving hydroxyurea, this target can be achieved
      with hydroxyurea alone or with the combination of hydroxyurea plus phlebotomies.
      However, the clinical implications of phlebotomy requirement under hydroxyurea
      therapy are unknown. The aim of this study was to evaluate the need for
      additional phlebotomies during the first five years of hydroxyurea therapy in 533
      patients with polycythemia vera. Patients requiring 3 or more phlebotomies per
      year (n=85, 16%) showed a worse hematocrit control than those requiring 2 or less
      phlebotomies per year (n=448, 84%). There were no significant differences between
      the two study groups regarding leukocyte and platelet counts. Patients requiring
      3 or more phlebotomies per year received significantly higher doses of
      hydroxyurea than the remaining patients. A significant higher rate of thrombosis
      was found in patients treated with hydroxyurea plus 3 or more phlebotomies per
      year compared to hydroxyurea with 0-2 phlebotomies per year (20.5% vs. 5.3% at 3
      years; P<0.0001). In multivariate analysis, independent risk factors for
      thrombosis were phlebotomy dependency (HR: 3.3, 95%CI: 1.5-6.9; P=0.002) and
      thrombosis at diagnosis (HR: 4.7, 95%CI: 2.3-9.8; P<0.0001). The proportion of
      patients fulfilling the European LeukemiaNet criteria of resistance/intolerance
      to hydroxyurea was significantly higher in the group requiring 3 or more
      phlebotomies per year (18.7% vs. 7.1%; P=0.001) mainly due to extrahematologic
      toxicity. In conclusion, phlebotomy requirement under hydroxyurea therapy
      identifies a subset of patients with increased proliferation of polycythemia vera
      and higher risk of thrombosis.

PMID- 27686378
TI  - An accurate, simple prognostic model consisting of age, JAK2, CALR, and MPL
      mutation status for patients with primary myelofibrosis.
AB  - In most patients with primary myelofibrosis, one of three mutually exclusive
      somatic mutations is detected. In approximately 60% of patients, the Janus kinase
      2 gene is mutated, in 20%, the calreticulin gene is mutated, and in 5%, the
      myeloproliferative leukemia virus gene is mutated. Although patients with mutated
      calreticulin or myeloproliferative leukemia genes have a favorable outcome, and
      those with none of these mutations have an unfavorable outcome, prognostication
      based on mutation status is challenging due to the heterogeneous survival of
      patients with mutated Janus kinase 2. To develop a prognostic model based on
      mutation status, we screened primary myelofibrosis patients seen at the MD
      Anderson Cancer Center, Houston, USA, between 2000 and 2013 for the presence of
      Janus kinase 2, calreticulin, and myeloproliferative leukemia mutations. Of 344
      primary myelofibrosis patients, Janus kinase 2V617F was detected in 226 (66%),
      calreticulin mutation in 43 (12%), and myeloproliferative leukemia mutation in 16
      (5%); 59 patients (17%) were triple-negatives. A 50% cut-off dichotomized Janus
      kinase 2-mutated patients into those with high Janus kinase 2V617F allele burden
      and favorable survival and those with low Janus kinase 2V617F allele burden and
      unfavorable survival. Patients with a favorable mutation status (high Janus
      kinase 2V617F allele burden/myeloproliferative leukemia/calreticulin mutation)
      and aged 65 years or under had a median survival of 126 months. Patients with one
      risk factor (low Janus kinase 2V617F allele burden/triple-negative or age >65
      years) had an intermediate survival duration, and patients aged over 65 years
      with an adverse mutation status (low Janus kinase 2V617F allele burden or triple
      negative) had a median survival of only 35 months. Our simple and easily applied
      age- and mutation status-based scoring system accurately predicted the survival
      of patients with primary myelofibrosis.

PMID- 27686379
TI  - Class P dye-decolorizing peroxidase gene: Degenerated primers design and
      phylogenetic analysis.
AB  - Dye-decolorizing peroxidases (DyPs) were classified as a new family of heme
      peroxidase in 2007. Produced by various bacteria, they are the first bacterial
      enzymes known able to degrade lignin and dyes, for which their application in
      waste treatment and pretreatment of lignocellulosic biomass could be envisaged.
      In this work, a PCR primer pair was created and tested that enabled the detection
      and quantification of a wide range of bacterial genes of P class DyP in complex
      matrices. In addition, a phylogenetic tree was built with all available sequences
      of DyP genes available, offering a first overview of their presence in the
      bacteria kingdom.

PMID- 27686380
TI  - Effects of field conditions on fecal microbiota.
AB  - Gut microbiota can provide great insight into host health, and studies of the gut
      microbiota in wildlife are becoming more common. However, the effects of field
      conditions on gut microbial samples are unknown. This study addresses the
      following questions: 1) How do environmental factors such as sunlight and insect
      infestations affect fecal microbial DNA? 2) How does fecal microbial DNA change
      over time after defecation? 3) How does storage method affect microbial DNA?
      Fresh fecal samples were collected, pooled, and homogenized from a family group
      of 6 spider monkeys, Ateles geoffroyi. Samples were then aliquoted and subjected
      to varying light conditions (shade, sun), insect infestations (limited or not
      limited by netting over the sample), and sample preservation methods (FTA - Fast
      Technology for Analysis of nucleic acid - cards, or freezing in liquid nitrogen
      then storing at -20 degrees C). Changes in the microbial communities under these
      conditions were assessed over 24h. Time and preservation method both effected
      fecal microbial community diversity and composition. The effect size of these
      variables was then assessed in relation to fecal microbial samples from 2 other
      primate species (Rhinopithecus bieti and R. brelichi) housed at different captive
      institutions. While the microbial community of each primate species was
      significantly different, the effects of time and preservation method still
      remained significant indicating that these effects are important considerations
      for fieldwork.

PMID- 27686381
TI  - Intestinal angina in a patient with hypertrophic obstructive cardiomyopathy: a
      case report.
AB  - BACKGROUND: Intestinal angina is characterized by recurrent postprandial
      abdominal pain and anorexia. Commonly, these symptoms are caused by severe
      stenosis of at least two vessels among the celiac and mesenteric arteries.
      However, intestinal perfusion is affected not only by the degree of arterial
      stenosis but also by systemic perfusion. We experienced a unique case of
      intestinal angina caused by relatively mild stenosis of the abdominal arteries
      complicated with hypertrophic obstructive cardiomyopathy. CASE PRESENTATION: We
      report an 86-year old Japanese man with hypertrophic obstructive cardiomyopathy
      and advanced atrioventricular block who was diagnosed with intestinal angina.
      Computed tomography showed mild stenosis of the celiac artery and severe stenosis
      of the inferior mesenteric artery, and these lesions were relatively mild
      compared with other reports. A dual-chamber pacemaker with right ventricular
      apical pacing was implanted to improve the obstruction of the left ventricular
      outflow tract. After implantation, the patient's abdominal symptoms diminished
      markedly, and improvement of the left ventricular outflow tract obstruction was
      observed. CONCLUSIONS: Although intestinal angina is generally defined by severe
      stenosis of at least two vessels among the celiac and mesenteric arteries, the
      present case suggests that hemodynamic changes can greatly affect intestinal
      perfusion and induce intestinal angina in the presence of mild stenosis of the
      celiac and mesenteric arteries.

PMID- 27686383
TI  - Series On Hospital Infections Introduction.

PMID- 27686384
TI  - National Symposium October 18,1997.

PMID- 27686382
TI  - Efficient evaluation of cellulose digestibility by Trichoderma reesei Rut-C30
      cultures in online monitored shake flasks.
AB  - BACKGROUND: Pretreated lignocellulosic biomass is considered as a suitable
      feedstock for the sustainable production of chemicals. However, the recalcitrant
      nature of cellulose often results in very cost-intensive overall production
      processes. A promising concept to reduce the costs is consolidated bioprocessing,
      which integrates in a single step cellulase production, cellulose hydrolysis, and
      fermentative conversion of produced sugars into a valuable product. This
      approach, however, requires assessing the digestibility of the applied celluloses
      and, thus, the released sugar amount during the fermentation. Since the released
      sugars are completely taken up by Trichoderma reesei Rut-C30 and the sugar
      consumption is stoichiometrically coupled to oxygen uptake, the respiration
      activity was measured to evaluate the digestibility of cellulose. RESULTS: The
      method was successfully tested on commercial cellulosic substrates identifying a
      correlation between the respiration activity and the crystallinity of the
      substrate. Pulse experiments with cellulose and cellulases suggested that the
      respiration activity of T. reesei on cellulose can be divided into two distinct
      phases, one limited by enzyme activity and one by cellulose-binding-sites. The
      impact of known (cellobiose, sophorose, urea, tween 80, peptone) and new
      (miscanthus steepwater) compounds enhancing cellulase production was evaluated.
      Furthermore, the influence of two different pretreatment methods, the OrganoCat
      and OrganoSolv process, on the digestibility of beech wood saw dust was tested.
      CONCLUSIONS: The introduced method allows an online evaluation of cellulose
      digestibility in complex and non-complex cultivation media. As the measurements
      are performed under fermentation conditions, it is a valuable tool to test
      different types of cellulose for consolidated bioprocessing applications.
      Furthermore, the method can be applied to identify new compounds, which influence
      cellulase production.

PMID- 27686386
TI  - Bacterial pathogens and endosymbionts in ticks.
AB  - Ticks collected from goats in northern Greece were tested for the presence of
      tick-borne bacteria. Among adult ticks, 37 (57.8%) were Rhipicephalus bursa, 11
      (17.2%) Dermacentor marginatus, 10 (15.6%) Ixodes ricinus, 3 (4.7%) Rhipicephalus
      sanguineus sensu lato and 2 (3.1%) Haemaphysalis parva; one (1.6%) Rhipicephalus
      spp. tick was nymph. Rickettsia monacensis, Rickettsia massilae, Anaplasma
      phagocytophilum and Anaplasma platys were detected in I. ricinus and Rh. bursa
      ticks. A variety of Coxiella-like endosymbionts were detected in all tick genera
      tested, forming distinct clades from Coxiella burnetii in the phylogenetic tree
      based on the 16S rRNA gene. An additional endosymbiont, Candidatus Midichloria
      mitochondrii, was detected in most of the I. ricinus ticks. Surveillance for
      human pathogens in ticks provides knowledge helpful for the public health, while
      further studies are needed to determine the role of endosymbionts in tick
      physiology, vector competence and probably in public health.

PMID- 27686387
TI  - High sensitivity of embryo-larval stage of the Mediterranean mussel, Mytilus
      galloprovincialis to metal pollution in combination with temperature increase.
AB  - The present work aimed to assess the effects of two widespread metallic
      pollutants, copper and silver, along with environmentally-realistic temperature
      increases, on embryo-larval development of the Mediterranean mussel Mytilus
      galloprovincialis. First, mussel embryos upon fertilization were exposed for 48 h
      to increasing concentrations of Cu (0.5-500 MUg/L) and Ag (0.1-100 MUg/L) at
      different temperatures (18, 20, 22 or 24  degrees C) in order to characterize
      toxicity of each toxicant at the different tested temperatures. Increasing
      concentrations of a Cu-Ag mixture were then tested in order to assess the mixture
      effect at different temperatures (18, 20 or 22  degrees C). Embryotoxicity was
      measured after 48 h of exposure (D-larvae stage) considering both the percentage
      of abnormalities and developmental arrest in D-larvae. The results suggest that
      the optimum temperature for mussel larvae development is 18  degrees C (12.65+/-
      1.6% malformations) and beyond 20  degrees C a steep increase of abnormal larvae
      was observed up to 100% at 24  degrees C. Ag was more toxic than Cu with a 50%
      effective concentration (EC50) at 18  degrees C of 6.58 MUg/L and 17.6 MUg/L,
      respectively. Temperature increased the toxicity of both metals as proved with
      the EC50 at 20  degrees C at 3.86 MUg/L and 16.28 MUg/L for Ag and Cu
      respectively. Toxic unit calculation suggests additive effects of Cu and Ag in
      mixture at 18 and 20  degrees C. These results highlight a possible impairment of
      M. galloprovincialis reproduction in the Mediterranean Sea in relation to
      increase of both pollutants and water temperature due to global warming.

PMID- 27686388
TI  - Aggregation of European storm-petrel (Hydrobates pelagicus ssp. melitensis)
      around cage fish farms. Do they benefit from the farms resources?
AB  - Cage aquaculture aggregates wild fauna due to food provision. Several seabirds
      frequent fish farms, including the European storm-petrel (Hydrobates pelagicus
      melitensis). This work investigates the presence of storm-petrels around two
      aquaculture areas interspersed between breeding colonies in western Mediterranean
      Sea. Contribution of aquaculture-derived resources to their diet was assessed.
      Storm-petrels were mist-netted at the colonies and marked by bleaching feathers.
      Density around aquaculture areas was estimated through visual counts. Marks
      recognition was conducted visually and by photo-capture. Storm-petrel
      regurgitates were used as target tissue to estimate diet sources contribution.
      Contribution of surface zooplankton, ichthyoplankton and aquaculture wastes was
      estimated through Bayesian mixing modelling combining carbon and nitrogen stable
      isotopes and fatty acids as biomarkers. Storm-petrel density was high in open-sea
      aquaculture area, but not observed around near shore farms. Temporal variability
      of storm-petrels density during the breeding season was linked to their
      reproductive phenology. Within the open-sea aquaculture area, bluefin tuna farm
      was more attractive for storm-petrels than seabream/seabass farms. Visual
      identification of bleaching marks was not useful. Photo-capture showed that 8.3%
      of the storm-petrels watched around farms were firstly trapped in some of the
      nearby colonies, and 91.7% were unmarked. Qualitative evidence of aquaculture
      derived wastes utilization was obtained. However, its estimated contribution was
      low (4.3%) when compared to ichthyoplankton (61.1%) or zooplankton (34.6%). The
      studied open-sea farms significantly aggregated storm-petrels along their entire
      breeding season. Storm-petrels got a slight profit from aquaculture resources.
      Nevertheless, some concerns arise regarding the cost/benefit balance of the
      interaction.

PMID- 27686389
TI  - Future aquafeeds may compromise reproductive fitness in a marine invertebrate.
AB  - Aquaculture of higher trophic level species is increasingly dependent on the use
      of terrestrial oil products. The input of terrestrially derived n-6
      polyunsaturated fatty acids (PUFA) into marine environments has subsequently
      increased, with unknown consequences for recipient species. We exposed a sea
      urchin, Heliocidaris erythrogramma to three experimental diets for 78 days: a
      high n-3 PUFA marine imitation treatment, a high n-6 PUFA "future aquafeed"
      treatment and an intermediate "current aquafeed" treatment. Female urchins fed
      the high n-6 PUFA diet produced larvae with lower survival rates than all other
      treatments. Males fed the high n-6 PUFA diet produced no viable sperm. Fatty acid
      composition in reproductive material revealed comprehensive biosynthetic and
      dietary sparing capabilities in H. erythrogramma. Despite this, the ratio of n-6
      PUFA to n-3 PUFA in reproductive tissue increased significantly with diet. We
      suggest alterations to this ratio is the likely mechanism of negative impact on
      larval development.

PMID- 27686390
TI  - Decision Activity in Parietal Cortex - Leader or Follower?
AB  - Katz and colleagues demonstrate that inactivating the primate lateral
      intraparietal area (LIP) spares visual motion decisions, even though these same
      decisions strongly modulate LIP neurons. This work is the latest addition to an
      intense effort spanning sensory modalities, animals, and techniques to understand
      which structures comprise the circuits responsible for interpreting sensory
      signals to make decisions.

PMID- 27686392
TI  - [Acute bacterial gastroenteritis: 729 cases recruited by a Primary Care national
      network].
AB  - OBJECTIVE: To determine the main clinical and epidemiological features of
      bacterial gastroenteritis in our environment. PATIENTS AND METHODS: An
      observational study of a Spanish population in 17 Autonomous Communities.
      Questionnaires of children with a stool positive culture to bacteria were
      collected over a one year period. A bivariate analysis was performed on the
      variables involved, as well as two multivariate models (for antibiotic treatment
      variables, and comparison Campylobacter/Salmonella). RESULTS: A total of 729
      bacterial gastroenteritis episodes were recorded in the 17 Spanish autonomous
      regions, of which 41.2% were girls and 58.8% boys. The median age was 3.41 years
      old (interquartile range 1.55 to 6.72). The bacteria isolated were 59.9%
      Campylobacter, 31.8% non-Typhi Salmonella, 2.7% Aeromonas, 2.4% Yersinia, and
      1.5% had more than one strain. Most infections (70%) were direct contacts, and
      food poisoning was less probable (25.9%). Salmonella is significantly less
      frequent than Campylobacter in children under the age of 3 years (adjusted OR
      0.61; 95%CI: 0.43 to 0.86; P=.005), and Campylobacter is more frequent in rural
      areas (adjusted OR 1.48; 95%CI: 1.07 to 2.07; P=.012). Antibiotic was prescribed
      in 33.2% of cases. There was a greater significant difference if stools contained
      blood or mucus (adjusted OR 1.53; 95%CI: 1.04 to 2.27; P=.031), if the symptoms
      lasted more than 7days (adjusted OR 2.81; 95%CI: 2.01 to 3.93; P<.000), or if the
      child was admitted to hospital (adjusted OR 1.95; 95%CI: 1.08 to 3.52; P=.027).
      CONCLUSIONS: The aetiology of bacterial diarrhoea in paediatrics is typical of
      that of a developed country. The transmission mechanism is mainly direct, and
      more cases than appropriate are treated with antibiotics.

PMID- 27686391
TI  - Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis
      during Vitiligo and May Serve as Biomarkers of Disease.
AB  - Vitiligo is an autoimmune disease of the skin that results in the destruction of
      melanocytes and the clinical appearance of white spots. Disease pathogenesis
      depends on IFN-gamma and IFN-gamma-induced chemokines to promote T-cell
      recruitment to the epidermis where melanocytes reside. The skin is a complex
      organ, with a variety of resident cell types. We sought to better define the
      microenvironment and distinct cellular contributions during autoimmunity in
      vitiligo, and we found that the epidermis is a chemokine-high niche in both a
      mouse model and human vitiligo. Analysis of chemokine expression in mouse skin
      showed that CXCL9 and CXCL10 expression strongly correlate with disease activity,
      whereas CXCL10 alone correlates with severity, supporting them as potential
      biomarkers for following disease progression. Further studies in both our mouse
      model and human patients showed that keratinocytes were the major chemokine
      producers throughout the course of disease, and functional studies using a
      conditional signal transducer and activator of transcription (STAT)-1 knockout
      mouse showed that IFN-gamma signaling in keratinocytes was critical for disease
      progression and proper autoreactive T-cell homing to the epidermis. In contrast,
      epidermal immune cell populations including endogenous T cells, Langerhans cells,
      and gammadelta T cells were not required. These results have important clinical
      implications, because topical therapies that target IFN-gamma signaling in
      keratinocytes could be safe and effective new treatments, and skin expression of
      these chemokines could be used to monitor disease activity and treatment
      responses.

PMID- 27686393
TI  - [In-vitro activity of azithromycin in faecal isolates of Aeromonas hydrophila].

PMID- 27686394
TI  - Indole modifies the central carbon flux in the anaerobic metabolism of
      Escherichia coli: application to the production of hydrogen and other
      metabolites.
AB  - Indole is a bicyclic signaling molecule with effects on both eukaryotic and
      prokaryotic cells. The majority of studies of indole action have been performed
      with bacteria cultured under aerobic conditions and little information is
      available about its effects under anaerobic conditions. Here the effect of the
      indole on anaerobic metabolism of Escherichia coli WDHL was studied. Indole in
      the range 0.5-8mM was added to the culture medium and cell growth, hydrogen and
      metabolite production were compared to cultures lacking indole. Results showed
      that while 8mM indole abolished growth completely, 4mM indole had a partial
      bacteriostatic effect and the maximum optical density of the culture decreased by
      44% compared to the control cultures. In addition, 4mM indole had an important
      effect on anaerobic metabolism. Hydrogen production increased from 650+/-115 to
      1137+/-343mL H2/L, and hydrogen yield increased from 0.45+/-0.1 to 0.94+/-0.34mol
      H2/mol glucose, compared to the control culture. Carbon flux was also affected
      and the composition of the final by-products changed. Lactate (41mM) was the main
      metabolite in the control cultures, whereas ethanol (56.2mM) and acetate (41.2mM)
      were the main metabolites in the cultures with 2mM indole. We conclude that the
      supplementation of E. coli cultures with exogenous indole is a simple and novel
      strategy to improve the production of hydrogen as well as other metabolites such
      as ethanol used as biofuels.

PMID- 27686395
TI  - Plant-assisted bioremediation of a historically PCB and heavy metal-contaminated
      area in Southern Italy.
AB  - A plant-assisted bioremediation strategy was applied in an area located in
      Southern Italy, close to the city of Taranto, historically contaminated by
      polychlorinated biphenyls (PCBs) and heavy metals. A specific poplar clone
      (Monviso) was selected for its ability to promote organic pollutant degradation
      in the rhizosphere, as demonstrated elsewhere. Chemical and microbiological
      analyses were performed at the time of poplar planting in selected plots at
      different distances from the trunk (0.25-1m) and at different soil depths (0-20
      and 20-40cm), at day 420. A significant decrease in PCB congeners and a reduction
      in all heavy metals was observed where the poplar trees were present. No evidence
      of PCB and heavy metal reduction was observed in the non poplar-vegetated soil.
      Microbial analyses (dehydrogenase activity, cell viability, microbial abundance)
      of the autochthonous microbial community showed an improvement in soil quality.
      In particular, microbial activity generally increased in the poplar-rhizosphere
      and a positive effect was observed in some cases at up to 1m distance from the
      trunk and up to 40cm depth. The Monviso clone was effective in promoting both a
      general decrease in contaminant occurrence and an increase in microbial activity
      in the chronically polluted area a little more than one year after planting.

PMID- 27686396
TI  - de Quervain's thyroiditis: A review of experience with surgery.
AB  - BACKGROUND: de Quervain's thyroiditis is an inflammatory condition of the thyroid
      mostly treated medically, rarely requiring surgical treatment. We intend to
      review the surgical experience with de Quervain's thyroiditis at a tertiary
      cancer center over a period of 22years. METHODS: A retrospective review of
      medical records from 1992 to 2014 at a tertiary cancer center was performed and
      all patients with a histopathological diagnosis of de Quervain's thyroiditis were
      included. RESULTS: Ten patients with a histopathological diagnosis of de
      Quervain's thyroiditis were included in the study. One patient in the study
      presented with dysphagia due to the goiter. The remaining patients presented with
      thyroid nodules. None presented with typical symptoms of the disease. Seven of
      the ten patients that had been evaluated for a goiter at an outside facility
      underwent fine needle aspiration cytology. Of the seven patients, one patient was
      suspected to have medullary carcinoma of the thyroid, two had follicular
      neoplasia, and the others had indeterminate nodules. Eight of the ten patients
      underwent surgery for suspected malignancy, with eight receiving a total
      thyroidectomy and two patients getting a thyroid lobectomy with isthmusectomy.
      Two patients had an abnormally hard gland to palpate during surgery with the
      others not having any suspicious findings. Seven of the ten of the patients had
      lymph node sampling from level 6 and all were benign on final pathology. The mean
      duration of post-operative follow-up was 15months. There was no morbidity
      associated with surgery in any of these patients with eight of the ten patients
      requiring thyroid hormone replacement. None of the patients needed further neck
      surgery for thyroid disease. CONCLUSION: de Quervain's thyroiditis is an
      inflammatory condition of the thyroid that is rarely treated surgically. However
      when presentation is atypical and the FNAC is inconclusive or is suspicious for a
      malignancy, patients receive surgery putting them at a risk for morbidity. Good
      clinical assessment with combined use of ultrasound with FNAC especially read by
      an experienced cytopathologist has the potential to reduce unnecessary operative
      intervention.

PMID- 27686397
TI  - Advances in nanomaterials and their applications in point of care (POC) devices
      for the diagnosis of infectious diseases.
AB  - Nanotechnology has gained much attention over the last decades, as it offers
      unique opportunities for the advancement of the next generation of sensing tools.
      Point-of-care (POC) devices for the selective detection of biomolecules using
      engineered nanoparticles have become a main research thrust in the diagnostic
      field. This review presents an overview on how the POC-associated nanotechnology,
      currently applied for the identification of nucleic acids, proteins and
      antibodies, might be further exploited for the detection of infectious pathogens:
      although still premature, future integrations of nanoparticles with biological
      markers that target specific microorganisms will enable timely therapeutic
      intervention against life-threatening infectious diseases.

PMID- 27686398
TI  - Transjugular Access for Endovascular Treatment of Immature Autogenous
      Arteriovenous Fistulae.
AB  - PURPOSE: To assess the feasibility and outcome of transjugular access for
      endovascular treatment of immature arteriovenous fistulae (AVFs). MATERIALS AND
      METHODS: Between August 2013 and January 2016, 90 patients (mean age, 64.5 y +/-
      12.8) underwent endovascular treatment of immature AVFs via transjugular access.
      The mean age of fistulae was 3.3 months +/- 1.8. Total procedure time and
      technical and clinical success rates of endovascular procedures were assessed.
      Primary and secondary patency rates were calculated according to the Kaplan-Meier
      method, and complications were assessed. RESULTS: All patients had inflow
      lesions, among which 19 (21.1%) had occlusions. The juxtaanastomotic segment was
      the most common site (44.3%). Transjugular access was successful in 83 patients
      (92.2%), and 7 required additional standard or transarterial access. The mean
      procedure time was 36.5 minutes. Technical and clinical success rates were 98.9%
      and 90.5%, respectively. Mean primary and secondary patency durations were 14.3
      months +/- 1.7 and 31.0 months +/- 0.7, respectively. Primary patency rates at 3,
      6, and 12 months were 84.4%, 67.3%, and 48.8%, respectively. Secondary patency
      rates at 6 and 18 months were 98.6% and 95.5%, respectively. Venous rupture
      occurred as a result of balloon inflation in 9 patients (10%), and was managed by
      balloon tamponade. There were no complications related to transjugular access
      during a mean follow-up period of 12.6 months. CONCLUSIONS: Transjugular access
      for angioplasty of immature AVFs is feasible and safe. Potential problems
      associated with access in the outflow vein could be avoided by transjugular
      access.

PMID- 27686399
TI  - Pharmacokinetic properties, in vitro metabolism and plasma protein binding of
      govaniadine an alkaloid isolated from Corydalis govaniana Wall.
AB  - Govaniadine (GOV) is an alkaloid isolated from Corydalis govaniana Wall. It has
      been reported to show a different number of biological activities including anti
      urease, leishmanicidal and antinociceptive. The present study aims to
      characterize the GOV in vitro metabolism after incubation with rat and human
      liver microsomes (RLM and HLM, respectively) and to evaluate its pharmacokinetic
      properties. The identification of GOV metabolites was conducted by different mass
      analyzers: a micrOTOF II-ESI-ToF Bruker Daltonics(r) and an amaZon-SL ion trap
      (IT) Bruker Daltonics(r). For the pharmacokinetic study of GOV in rats after
      intravenous administration, a LC-MS/MS method was developed and applied to. The
      analyses were performed using an Acquity UPLC(r) coupled to an Acquity TQD
      detector equipped with an ESI interface. The liver microsomal incubation resulted
      in new O-demethylated, di-hydroxylated and mono-hydroxylated compounds. Regarding
      the method validation, the calibration curve was linear over the concentration
      range of 2.5-3150.0ngmL-1, with a lower limit of quantitation (LLOQ) of 2.5ngmL
      1. This method was successfully applied to a pharmacokinetic study. The profile
      was best fitted to a two-compartment model, the first phase with a high
      distribution rate constant (alpha) 0.139+/-0.086min-1, reflected by the short
      distribution half-life (t1/2alpha) 9.2+/-8.9min and the later one, with an
      elimination half-life (t1/2beta) 55.1+/-37.9min. The main plasma protein binding
      was 96.1%. This is a first report in this field and it will be useful for further
      development of govaniadine as a drug candidate.

PMID- 27686400
TI  - Sculpting the labyrinth: Morphogenesis of the developing inner ear.
AB  - The vertebrate inner ear is a precision sensory organ, acting as both a
      microphone to receive sound and an accelerometer to detect gravity and motion. It
      consists of a series of interlinked, fluid-filled chambers containing patches of
      sensory epithelia, each with a specialised function. The ear contains many
      different differentiated cell types with distinct morphologies, from the flask
      shaped hair cells found in thickened sensory epithelium, to the thin squamous
      cells that contribute to non-sensory structures, such as the semicircular canal
      ducts. Nearly all cell types of the inner ear, including the afferent neurons
      that innervate it, are derived from the otic placode, a region of cranial
      ectoderm that develops adjacent to the embryonic hindbrain. As the ear develops,
      the otic epithelia grow, fold, fuse and rearrange to form the complex three
      dimensional shape of the membranous labyrinth. Much of our current understanding
      of the processes of inner ear morphogenesis comes from genetic and
      pharmacological manipulations of the developing ear in mouse, chicken and
      zebrafish embryos. These traditional approaches are now being supplemented with
      exciting new techniques-including force measurements and light-sheet microscopy
      that are helping to elucidate the mechanisms that generate this intricate organ
      system.

PMID- 27686401
TI  - Relationships among plasma granzyme B level, pruritus and dermatitis in patients
      with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease
      characterized by skin barrier dysfunction, allergic inflammation and intractable
      pruritus resistant to conventional antipruritic treatments, including H1
      antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by
      cytotoxic T lymphocytes and natural killer cells that have been shown to modulate
      inflammation. However, the relationship between Gzms and pathology in AD remains
      unclear. OBJECTIVE: This study assessed the correlation between plasma GzmB
      levels and severity of pruritus and dermatitis, in AD patients. METHODS: Plasma
      was collected from 46 patients with AD, 24 patients with psoriasis, and 30
      healthy controls. AD severity was assessed with the scoring atopic dermatitis
      (SCORAD) index, psoriasis severity with the psoriasis area and severity index
      (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB
      and gastrin releasing peptide (GRP) levels were measured by enzyme-linked
      immunosorbent assays. RESULTS: Plasma GzmB concentrations were significantly
      higher in patients with AD and psoriasis than in healthy controls. Correlation
      analyses showed that plasma GzmB concentrations positively correlated with SCORAD
      and serum levels of severity markers such as thymus and activation-regulated
      chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of
      GRP, an itch-related peptide, were higher in patients with AD, positively
      correlating with VAS score and plasma GzmB level. In addition, plasma GzmB
      concentration was significantly lower in the treatment group than the untreated
      group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score
      and PASI score in patients with psoriasis. In contrast to the results of plasma
      GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups,
      and showed no correlations with VAS score and SCORAD index in patients with AD.
      CONCLUSION: Plasma GzmB levels may reflect the degree of pruritus and dermatitis
      in patients with AD.

PMID- 27686402
TI  - Exercise promotes IL-6 release from legs in older men with minor response to
      unilateral immobilization.
AB  - Physical inactivity is a major contributor to low-grade systemic inflammation.
      Most of the studies characterizing interleukin-6 (IL-6) and tumour necrosis
      factor-alpha (TNF-alpha) release from exercising legs have been done in young,
      healthy men, but studies on inactivity in older people are lacking. The impact of
      14 days of one-leg immobilization (IM) on IL-6 and TNF-alpha release during
      exercise in comparison to the contralateral control (CON) leg was investigated.
      Fifteen healthy men (age 68.1 +/- 1.1 year (mean +/- SEM); BMI 27.0 +/- 0.4
      kg.m(2); VO2max 33.3 +/- 1.6 ml.kg(-1).min(-1)) performed 45 min of two-leg
      dynamic knee extensor exercise at 19.5 +/- 0.9 W. Arterial and femoral venous
      blood samples from the CON and the IM legs were collected every 15 min during
      exercise, and thigh blood flow was measured with ultrasound Doppler. Arterial
      plasma IL-6 concentration increased with exercise (rest vs. 45 min, main effect p
      < .05). IL-6 release increased with exercise (rest vs. 30 min, main effect p <
      .05). Furthermore, IL-6 release was borderline (main effect, p = .085, effect
      size 0.28) higher in the IM leg compared to the CON leg (288 (95% CI: 213-373)
      vs. 220 (95% CI: 152-299) pg.min(-1), respectively). There was no release of TNF
      alpha in either leg and arterial concentrations remained unchanged during
      exercise (p > .05). In conclusion, exercise induces more pronounced IL-6
      secretion in healthy older men. Two weeks of unilateral immobilization on the
      other hand had only a minor influence on IL-6 release. Neither immobilization nor
      exercise had an effect on TNF-alpha release across the working legs in older men.

PMID- 27686403
TI  - Influence of a caffeine mouth rinse on sprint cycling following glycogen
      depletion.
AB  - Attenuated performance during intense exercise with limited endogenous
      carbohydrate (CHO) is well documented. Therefore, this study examined whether
      caffeine (CAF) mouth rinsing would augment performance during repeated sprint
      cycling in participants with reduced endogenous CHO. Eight recreationally active
      males (aged 23 +/- 2 yr, body mass 84 +/- 4 kg, stature 178 +/- 7 cm)
      participated in this randomized, single-blind, repeated-measures crossover
      investigation. Following familiarization, participants attended two separate
      evening glycogen depletion sessions. The following morning, participants
      completed five, 6 s sprints on a cycle ergometer (separated by 24 s active
      recovery), with mouth rinsing either (1) a placebo solution or (2) a 2% CAF
      solution. During a fifth visit, participants completed the sprints without prior
      glycogen depletion. Repeated-measures ANOVA identified significant main effect of
      condition (CAF, placebo, and control [P < .05; effect size (ES) = 0.850-0.897]),
      sprint (1-5 [P < .005; ES = 0.871-0.986]), and interaction (condition * sprint [P
      < .05; ES = 0.831-0.846]), for peak and mean power. The control condition
      exhibited the highest peak power (overall mean 760 +/- 77 W) and mean power
      (overall mean 699 +/- 83W) over the five sprints (P < .001 in both instances).
      CAF peak power (overall mean 643 +/- 79 W) was significantly greater than placebo
      (mean 573 +/- 79 W [P < .05; ES = 0.850]). Additionally, CAF mean power (overall
      mean 589 +/- 80 W) was significantly greater than placebo (519 +/- 82 W [P < .05;
      ES = 0.397]). These data indicate that mouth rinsing a caffeinated solution
      reduces decrements caused by CHO reduction, which may benefit athletes wishing to
      train in a low-CHO state. 

PMID- 27686404
TI  - Evaluation of the performance of high temperature conversion reactors for
      compound-specific oxygen stable isotope analysis.
AB  - In this study conversion conditions for oxygen gas chromatography high
      temperature conversion (HTC) isotope ratio mass spectrometry (IRMS) are
      characterised using qualitative mass spectrometry (IonTrap). It is shown that
      physical and chemical properties of a given reactor design impact HTC and thus
      the ability to accurately measure oxygen isotope ratios. Commercially available
      and custom-built tube-in-tube reactors were used to elucidate (i) by-product
      formation (carbon dioxide, water, small organic molecules), (ii) 2nd sources of
      oxygen (leakage, metal oxides, ceramic material), and (iii) required reactor
      conditions (conditioning, reduction, stability). The suitability of the available
      HTC approach for compound-specific isotope analysis of oxygen in volatile organic
      molecules like methyl tert-butyl ether is assessed. Main problems impeding
      accurate analysis are non-quantitative HTC and significant carbon dioxide by
      product formation. An evaluation strategy combining mass spectrometric analysis
      of HTC products and IRMS 18O/16O monitoring for future method development is
      proposed.

PMID- 27686405
TI  - Tp53 gene p72R polymorphism in chronic lymphocytic leukemia: incidence and
      clinical significance amongst cases with unmutated immunoglobulin receptors.

PMID- 27686407
TI  - Discovery and characterization of miRNAs in mouse thymus responses to ionizing
      radiation by deep sequencing.
AB  - To investigate the potential regulatory roles of microRNA (miRNA) in mouse
      response to ionizing radiation (IR)-induced thymus injury, miRNA expression
      profiles of mouse thymus with or without IR were analyzed using deep sequencing
      technology. Potential target candidates of the identified miRNA were predicted
      using RNAhybrid and miRanda. Differently expressed miRNA targets functional
      annotation and pathways were noted using Swiss-Prot, Gene Ontology (GO), Clusters
      of Orthologous Groups (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and
      non-redundant (NR) databases. In this study, there were 112 differently expressed
      miRNAs identified, including 45 known mature and 67 novel miRNAs, which meanwhile
      contained 77 up-regulated and 35 down-regulated miRNAs. The results of
      quantitative RT-polymerase chain reaction (qRT-PCR) verification were in
      agreement with the sequencing analysis. And the target genes of miRNA were
      annotated. These results revealed the differences of miRNA expression, further
      extended the biological knowledge and greatly facilitated future studies on the
      function of miRNA in IR-induced thymus injury.

PMID- 27686406
TI  - Inhibitory mechanism of peptides with a repeating hydrophobic and hydrophilic
      residue pattern on interleukin-10.
AB  - Interleukin 10 (IL-10) is a cytokine that is able to downregulate inflammation.
      Its overexpression is directly associated with the difficulty in the clearance of
      chronic viral infections, such as chronic hepatitis B, hepatitis C and HIV
      infection, and infection-related cancer. IL-10 signaling blockade has been
      proposed as a promising way of clearing chronic viral infection and preventing
      tumor growth in animal models. Recently, we have reported that peptides with a
      helical repeating pattern of hydrophobic and hydrophilic residues are able to
      inhibit IL-10 significantly both in vitro and in vivo. 1 In this work, we seek to
      further study the inhibiting mechanism of these peptides using sequence-modified
      peptides. As evidenced by both experimental and molecular dynamics simulation in
      concert the N-terminal hydrophobic peptide constructed with repeating hydrophobic
      and hydrophilic pattern of residues is more likely to inhibit IL10. In addition,
      the sequence length and the ability of protonation are also important for
      inhibition activity.

PMID- 27686408
TI  - Impact of T-cell-specific Smad4 deficiency on the development of autoimmune
      diabetes in NOD mice.
AB  - Type 1 diabetes results from autoimmune-mediated pancreatic beta-cell destruction
      and transforming growth factor-beta (TGF-beta) is known to play a preventive role
      in type 1 diabetes in non-obese diabetic (NOD) mice. In this study, we
      investigated the role of Smad4, a key molecule for Smad-dependent TGF-beta
      signaling, in T cells of NOD mice in the pathogenesis of autoimmune diabetes. We
      generated T-cell-specific Smad4 knockout (Smad4 tKO) NOD mice and assessed the
      pathological and immunological changes. Smad4 tKO showed earlier onset and
      increased incidence of diabetes than wild type (WT) NOD mice. Pathological
      features such as insulitis, anti-glutamic acid decarboxylase auto-antibody levels
      and serum IFN-gamma levels were significantly increased in Smad4 tKO compared
      with WT NOD mice. Proportion and number of activated/memory CD4+ T cell were
      significantly increased in pancreatic lymph nodes of Smad4 tKO compared with WT
      NOD mice. However, the proportion and function of regulatory T cells was not
      different. Effector CD4+ T cells from Smad4 tKO were more resistant to
      suppression by regulatory T cells than effector cells from WT NOD mice. The
      proliferative potential of effector T cells from Smad4 tKO was significantly
      elevated compared with WT NOD mice, and activation of sterol regulatory element
      binding protein-1c (SREBP-1c) in T cells of Smad4 tKO NOD mice was correlated
      with this proliferative activity. We conclude that Smad4 deletion in T cells of
      NOD mice accelerated the development of autoimmune diabetes and increased the
      incidence of the disease by dysregulation of T cell activation at least in part
      via SREBP-1c activation.

PMID- 27686409
TI  - Single-molecule visualization of dynamic transitions of pore-forming peptides
      among multiple transmembrane positions.
AB  - Research on the dynamics of single-membrane proteins remains underdeveloped due
      to the lack of proper approaches that can probe in real time the protein's
      insertion depth in lipid bilayers. Here we report a single-molecule visualization
      method to track both vertical insertion and lateral diffusion of membrane
      proteins in supported lipid bilayers by exploiting the surface-induced
      fluorescence attenuation (SIFA) of fluorophores. The attenuation follows a d-4
      dependency, where d is the fluorophore-to-surface distance. The method is
      validated by observing the antimicrobial peptide LL-37 to transfer among five
      transmembrane positions: the surface, the upper leaflet, the centre, the lower
      leaflet and the bottom of the lipid bilayer. These results demonstrate the power
      of SIFA to study protein-membrane interactions and provide unprecedented in-depth
      understanding of molecular mechanisms of the insertion and translocation of
      membrane proteins.

PMID- 27686410
TI  - Treating epileptic emergencies - pharmacological advances.
AB  - INTRODUCTION: Epileptic emergencies are frequently encountered and include ictal
      events as status epilepticus or seizure clusters, and non-ictal situations like
      postictal psychosis or acute drug side effects. The aim of this review was to
      describe recent pharmacological advances in the treatment of epileptic
      emergencies. Areas covered: Based on clinically relevant questions, a literature
      search was performed. The search showed that most pharmacological advances have
      been made in management of status epilepticus, where substantial literature has
      accumulated on several AEDs with potentially less side-effects than the
      traditional choices. The use of these drugs; valproate, levetiracetam, and
      lacosamide, was therefore made the main focus of this review. Pharmacological
      advances in treatment of other epileptic emergencies were scarce, and were
      therefore covered more briefly in the Expert Opinion section. Expert opinion:
      This section outlines our current practice in management of status epilepticus
      and seizures clusters. Our opinion is that valproate is an equal alternative as
      second line treatment to fosphenytoin, with levetiracetam considered a good
      choice in frail and elderly patients. Due to the lack of literature, lacosamide
      is used mainly as a 2nd line drug after the failure of valproate, fosphenytoin
      and levetiracetam. Our review underlines the need for more research in management
      of epileptic emergencies.

PMID- 27686411
TI  - Management of a Patient With Acute Acetabular Labral Tear and Femoral Acetabular
      Impingement With Intra-articular Steroid Injection and a Neuromotor Training
      Program.
AB  - Study Design Case report. Background Intra-articular hip pathologies can be
      difficult to diagnose, and evidence to guide physical therapy interventions is
      lacking. The purpose of this case report is to describe a clinical pathway for
      conservative management of a patient with an acute acetabular labral tear and
      femoroacetabular impingement. Case Description The patient was an 18-year-old
      woman with recent onset of right groin pain who underwent intra-articular
      corticosteroid injection and therapeutic exercise for the management of an acute
      acetabular labral tear identified on radiographic imaging. Prior to physical
      therapy, the patient received an intra-articular hip injection for diagnostic
      purposes and pain relief. Upon initial evaluation, the patient presented with
      improved pain but with continued kinesthetic deficits, inflexibility, muscle
      imbalances, and reproduction of symptoms with end-range hip motions. A physical
      therapy plan was implemented using neuromuscular re-education to address her
      continued impairments. Outcomes Marked improvements were noted at discharge and 6
      month follow-up for pain, strength, and function as demonstrated on the Patient
      Specific Functional Scale, global rating of change scale, and International Hip
      Outcome Tool-33. Discussion This case demonstrates a clinical pathway for
      collaborative medical management of a patient with confirmed intra-articular
      pathology. Details illustrate the clinical reasoning and rationale used to guide
      the clinical decision-making process. Level of Evidence Therapy, level 4. J
      Orthop Sports Phys Ther 2016;46(11):965-975. Epub 29 Sep 2016.
      doi:10.2519/jospt.2016.6573.

PMID- 27686412
TI  - The Association of Ankle Dorsiflexion Range of Motion With Hip and Knee
      Kinematics During the Lateral Step-down Test.
AB  - Study Design Controlled laboratory study. Background Altered hip and knee
      kinematics have been associated with several knee disorders, including anterior
      cruciate ligament tear, patellofemoral pain, and iliotibial band syndrome.
      Limited ankle dorsiflexion (DF) range of motion (ROM), which has been linked with
      some of these disorders, has also been associated with altered knee kinematics.
      Objective To explore the association of ankle DF ROM with hip and knee kinematics
      during a step-down task. Methods Thirty healthy participants underwent a 3-D
      analysis of hip and knee kinematics during a lateral step-down test, followed by
      measurement of ankle DF ROM in weight bearing (WB) and non-weight bearing (NWB).
      Participants were dichotomized using the median values into low- and high-DF
      subgroups within both WB and NWB. Hip and knee kinematics were compared between
      the low- and high-DF subgroups. Results Participants in the low-DF subgroups
      exhibited greater peak hip adduction (WB, P = .02; NWB, P<.01) and greater peak
      knee external rotation (WB, P = .02; NWB, P<.01) compared with participants in
      the high-DF subgroups. In addition, participants in the low-DF WB subgroup
      exhibited decreased peak knee flexion compared with participants in the high-DF
      WB subgroup (P<.01). Conclusion Individuals with lower ankle DF ROM exhibited hip
      and knee kinematics previously associated with several knee disorders, suggesting
      that this impairment may be involved in the pathogenesis of the same disorders.
      Assessment of ankle DF ROM may be useful as part of a preparticipation screening.
      Furthermore, deficits in ankle DF ROM may need to be addressed in individuals
      with altered movement patterns. J Orthop Sports Phys Ther 2016;46(11):-1. Epub 29
      Sep 2016. doi:10.2519/jospt.2016.6621.

PMID- 27686413
TI  - Pelvic Rotation in Femoroacetabular Impingement Is Decreased Compared to Other
      Symptomatic Hip Conditions.
AB  - Study Design Cross-sectional, case-control design. Background Pelvic movement has
      been considered a possible discriminating parameter associated with
      femoroacetabular impingement (FAI) symptom onset. Decreased pelvic rotation has
      been found during squatting in people with FAI when compared to people with
      healthy hips. However, it is possible that changes in pelvic movement may occur
      in other hip conditions because of pain and may not be specific to FAI.
      Objectives To compare sagittal pelvic rotation during hip flexion and in sitting
      between people with FAI and people with other symptomatic hip conditions. Methods
      Thirty people with symptomatic FAI, 30 people with other symptomatic hip
      conditions, and 20 people with healthy hips participated in the study. Sagittal
      pelvic rotation was calculated based on measures of pelvic alignment in standing,
      hip flexion to 45 degrees  and 90 degrees , and sitting. Results There were
      significant differences in sagittal pelvic rotation among the 3 groups in all
      conditions (P<.05). Post hoc analyses revealed that participants in the
      symptomatic FAI group had less pelvic rotation during hip flexion to 45 degrees 
      and 90 degrees  compared to participants in the other symptomatic hip conditions
      group and the hip-healthy group (mean difference, 1.2 degrees -1.9 degrees ). In
      sitting, participants in the other symptomatic hip conditions group had less
      posterior pelvic rotation compared to those in the hip-healthy group (mean
      difference, 3.9 degrees ). Conclusion People with symptomatic FAI have less
      posterior pelvic rotation during hip flexion when compared to people with other
      symptomatic hip conditions and those with healthy hips. Level of Evidence
      Diagnosis, level 4. J Orthop Sports Phys Ther 2016;46(11):957-964. Epub 29 Sep
      2016. doi:10.2519/jospt.2016.6713.

PMID- 27686414
TI  - Feasibility of electromagnetically guided transjugular intrahepatic portosystemic
      shunt procedure.
AB  - OBJECTIVES: To develop an electromagnetic navigation technology for transjugular
      intrahepatic portosystemic shunt (TIPS) creation and translate it from phantom to
      an in-vivo large animal setting. MATERIAL AND METHODS: A custom-designed device
      for TIPS creation consisting of a stylet within a 5 French catheter as well as a
      software prototype were developed that allow real-time tip tracking of both
      stylet and catheter using an electromagnetic tracking system. Feasibility of
      navigated TIPSS creation was tested in a phantom by two interventional
      radiologists (A/B) followed by in-vivo testing evaluation in eight domestic pigs.
      Procedure duration and number of attempts needed for puncture of the portal vein
      were recorded. RESULTS: In the phantom setting, intervention time to gain access
      to the portal vein (PV) was 144 +/- 67 s (A) and 122 +/- 51 s (B), respectively.
      In the in-vivo trials, TIPS could be successfully completed in five out of eight
      animals. Mean time for the complete TIPS was 245 +/- 205 minutes with a notable
      learning curve towards the last animal. CONCLUSIONS: TIPS creation with the use
      of electromagnetic tracking technology proved to be feasible in-vitro as well as
      in-vivo. The system may be useful to facilitate challenging TIPSS procedures.

PMID- 27686415
TI  - Comparison of standard, quantitative and digital PCR in the detection of
      enterotoxigenic Bacteroides fragilis.
AB  - Gut colonization with enterotoxigenic Bacteroides fragilis (ETBF) appears to be
      associated with the development of colorectal cancer. However, differences in
      carriage rates are seen with various testing methods and sampling sites. We
      compared standard PCR, SYBR green and TaqMan quantitative PCR (qPCR) and digital
      PCR (dPCR) in detecting the B. fragilis toxin (bft) gene from cultured ETBF, and
      from matched luminal and faecal stool samples from 19 colorectal cancer patients.
      Bland-Altman analysis found that all three quantitative methods performed
      comparably in detecting bft from purified bacterial DNA, with the same limits of
      detection (<1 copy/MUl). However, SYBR qPCR under-performed compared to TaqMan
      qPCR and dPCR in detecting bft in clinical stool samples; 13/38 samples were
      reported positive by SYBR, compared to 35 and 36 samples by TaqMan and dPCR,
      respectively. TaqMan qPCR and dPCR gave bft copy numbers that were 48-fold and 75
      fold higher for the same samples than SYBR qPCR, respectively (p < 0.001). For
      samples that were bft-positive in both fecal and luminal stools, there was no
      difference in relative abundance between the sites, by any method tested. From
      our findings, we recommend the use of TaqMan qPCR as the preferred method to
      detect ETBF from clinical stool samples.

PMID- 27686416
TI  - Allochthonous carbon is a major regulator to bacterial growth and community
      composition in subarctic freshwaters.
AB  - In the subarctic region, climate warming and permafrost thaw are leading to
      emergence of ponds and to an increase in mobility of catchment carbon. As carbon
      of terrestrial origin is increasing in subarctic freshwaters the resource pool
      supporting their microbial communities and metabolism is changing, with
      consequences to overall aquatic productivity. By sampling different subarctic
      water bodies for a one complete year we show how terrestrial and algal carbon
      compounds vary in a range of freshwaters and how differential organic carbon
      quality is linked to bacterial metabolism and community composition. We show that
      terrestrial drainage and associated nutrients supported higher bacterial growth
      in ponds and river mouths that were influenced by fresh terrestrial carbon than
      in large lakes with carbon from algal production. Bacterial diversity, however,
      was lower at sites influenced by terrestrial carbon inputs. Bacterial community
      composition was highly variable among different water bodies and especially
      influenced by concentrations of dissolved organic carbon (DOC), fulvic acids,
      proteins and nutrients. Furthermore, a distinct preference was found for
      terrestrial vs. algal carbon among certain bacterial tribes. The results
      highlight the contribution of the numerous ponds to cycling of terrestrial carbon
      in the changing subarctic and arctic regions.

PMID- 27686417
TI  - Sharp transitions in low-number quantum dots Bayesian magnetometry.
AB  - We consider Bayesian estimate of static magnetic field, characterized by a prior
      Gaussian probability distribution, in systems of a few electron quantum dot spins
      interacting with infinite temperature spin environment via hyperfine interaction.
      Sudden transitions among optimal states and measurements are observed. Usefulness
      of measuring occupation levels is shown for all times of the evolution, together
      with the role of entanglement in the optimal scenario. For low values of magnetic
      field, memory effects stemming from the interaction with environment provide
      limited metrological advantage.

PMID- 27686418
TI  - Treatment with Piribedil and Memantine Reduces Noise-Induced Loss of Inner Hair
      Cell Synaptic Ribbons.
AB  - Noise overstimulation can induce loss of synaptic ribbons associated with loss of
      Inner Hair Cell - Auditory Nerve synaptic connections. This study examined if
      systemic administration of Piribedil, a dopamine agonist that reduces the sound
      evoked auditory nerve compound action potential and/or Memantine, an NMDA
      receptor open channel blocker, would reduce noise-induced loss of Inner Hair Cell
      ribbons. Rats received systemic Memantine and/or Piribedil for 3 days before and
      3 days after a 3 hour 4 kHz octave band noise at 117 dB (SPL). At 21 days
      following the noise there was a 26% and 38% loss of synaptic ribbons in regions
      5.5 and 6.5 mm from apex, respectively, elevations in 4-, 8- and 20 kHz tonal ABR
      thresholds and reduced dynamic output at higher intensities of stimulation.
      Combined treatment with Piribedil and Memantine produced a significant reduction
      in the noise-induced loss of ribbons in both regions and changes in ABR
      sensitivity and dynamic responsiveness. Piribedil alone gave significant
      reduction in only the 5.5 mm region and Memantine alone did not reach
      significance in either region. Results identify treatments that could prevent the
      hearing loss and hearing disorders that result from noise-induced loss of Inner
      Hair Cell - Auditory Nerve synaptic connections.

PMID- 27686419
TI  - High-mechanical-frequency characteristics of optomechanical crystal cavity with
      coupling waveguide.
AB  - Optomechanical crystals have attracted great attention recently for their ability
      to realize strong photon-phonon interaction in cavity optomechanical systems. By
      far, the operation of cavity optomechanical systems with high mechanical
      frequency has to employ tapered fibres or one-sided waveguides with circulators
      to couple the light into and out of the cavities, which hinders their on-chip
      applications. Here, we demonstrate larger-centre-hole nanobeam structures with on
      chip transmission-coupling waveguide. The measured mechanical frequency is up to
      4.47 GHz, with a high mechanical Q-factor of 1.4 * 103 in the ambient
      environment. The corresponding optomechanical coupling rate is calculated and
      measured to be 836 kHz and 1.2 MHz, respectively, while the effective mass is
      estimated to be 136 fg. With the transmission waveguide coupled structure and a
      small footprint of 3.4 MUm2, this simple cavity can be directly used as
      functional components or integrated with other on-chip devices in future
      practical applications.

PMID- 27686420
TI  - Cytotoxic new furoquinoline alkaloid isolated from Ammi majus L. growing in
      Egypt.
AB  - Two alkaloids of the furoquinoline-type were isolated from Ammi majus L.; a new
      one and was identified as 4-hydro-7-hydroxy-8-methoxyfuroquinoline (1), and the
      other was isolated for the second time from nature and was identified as 4-hydro
      7-hydroxy-8-prenyloxyfuroquinoline (2). The structures of the isolated compounds
      were established and confirmed by 1D and 2D NMR spectroscopy including 1H, 13C
      NMR, COSY, HSQC and HMBC, while the exact masses were confirmed by HRESI/MS. The
      cytotoxic activity of the isolated compounds (1 and 2) was evaluated against HepG
      2, PC-3, A-549 and MCF-7 and the obtained results suggested selective
      antiproliferative and cytotoxic effects, with IC50 = 230.2 and 326.5 MUM against
      HepG-2 and MCF-7, respectively, for compound (1). While, compound (2) recorded
      IC50 = 234.2 MUM against MCF-7.

PMID- 27686421
TI  - A Case Study of Engaging Hard-to-Reach Participants in the Research Process:
      Community Advisors on Research Design and Strategies (CARDS)(r).
AB  - Lack of diversity among study participants in clinical research limits progress
      in eliminating health disparities. The engagement of lay stakeholders, such as
      patient or community advisory boards (CABs), has the potential to increase
      recruitment and retention of underrepresented groups by providing a structure for
      gathering feedback on research plans and materials from this target population.
      However, many CABs intentionally recruit prominent stakeholders who are connected
      to or comfortable with research and academia and thus may not accurately
      represent the perspectives of underrepresented groups who have been labeled hard
      to-reach, including racial minorities and low-income or low-literacy populations.
      We developed a partnership between the University of Wisconsin-Madison School of
      Nursing and two community centers to deliberately engage hard-to-reach people in
      two lay advisory groups, the Community Advisors on Research Design and Strategies
      (CARDS)(r). Community center staff recruited the CARDS from center programs,
      including parenting and childcare programs, women's support groups, food
      pantries, and senior meal programs. The CARDS model differs from other CABs in
      its participants, processes, and outcomes. Since 2010, the CARDS have met monthly
      with nurses and other researchers, helping them understand how research processes
      and the language, tone, appearance, and organization of research materials can
      discourage people from enrolling in clinical studies. We have successfully used
      the CARDS model to bring hard-to-reach populations into the research process and
      have sustained their participation. The model represents a promising strategy for
      increasing the diversity of participants in clinical research. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27686422
TI  - A trophic framework for animal origins.
AB  - Metazoans emerged in a microbial world and play a unique role in the biosphere as
      the only complex multicellular eukaryotes capable of phagocytosis. While the
      bodyplan and feeding mode of the last common metazoan ancestor remain unresolved,
      the earliest multicellular stem-metazoans likely subsisted on picoplankton
      (planktonic microbes 0.2-2 MUm in diameter) and dissolved organic matter (DOM),
      similarly to modern sponges. Once multicellular stem-metazoans emerged, they
      conceivably modulated both the local availability of picoplankton, which they
      preferentially removed from the water column for feeding, and detrital particles
      2-100 MUm in diameter, which they expelled and deposited into the benthos as
      waste products. By influencing the availability of these heterotrophic food
      sources, the earliest multicellular stem-metazoans would have acted as ecosystem
      engineers, helping create the ecological conditions under which other metazoans,
      namely detritivores and non-sponge suspension feeders incapable of subsisting on
      picoplankton and DOM, could emerge and diversify. This early style of metazoan
      feeding, specifically the phagocytosis of small eukaryotic prey, could have also
      encouraged the evolution of larger, even multicellular, eukaryotic forms less
      prone to metazoan consumption. Therefore, the first multicellular stem-metazoans,
      through their feeding, arguably helped bridge the strictly microbial food webs of
      the Proterozoic Eon (2.5-0.541 billion years ago) to the more macroscopic,
      metazoan-sustaining food webs of the Phanerozoic Eon (0.541-0 billion years ago).

PMID- 27686423
TI  - Editorial Comment to Practical ex-vivo evaluation of application of surgical
      clips to sutures during re-approximation of renal tissue in partial nephrectomy.

PMID- 27686424
TI  - Engineering 1,3-Alternate Calixcarbazole for Recognition and Sensing of Bisphenol
      F in Water.
AB  - Herein, we report a carbazolyl tubular macrocycle (3), which possesses a "pi
      tube" capable of encapsulating and sensing bisphenol F (BPF), which is a toxic
      industrial material. In this work, the synthesis of 3, its conformation in
      solution as well as its binding property to BPF have been investigated. Nuclear
      magnetic resonance (NMR), ultraviolet-visible light (UV-vis), fluorescence
      spectra, and molecular modeling studies reveal that the "pi-tube" of 3 in 1,3
      alternate conformation could encapsulate BPF with 1:1 binding stoichiometry in
      water, with its orthogonal tweezers sandwiching the two phenol units of BPF.
      Moreover, 3 could serve as a sensitive fluorescent probe for BPF (limitation of
      detection = 157 nM).

PMID- 27686425
TI  - Saint Ioannis Lampadistis, the first possible case of blindness due to organic
      mercury poisoning in history.
AB  - Saint Ioannis Lampadistis is a Cypriot saint of the Greek Orthodox Church, widely
      venerated in his island of origin. He lived during the 11th century and was
      blinded by ingesting contaminated fish in the mountainous area of Galata,
      withdrew from civil life when he was 18, and died at the age of 22. The reason
      for his blindness remains unknown, though it is widely attributed to an unknown
      poison related to the copper mines of the region. As fish is the end reservoir of
      organic mercury, it is quite possible that his blindness was the result of heavy
      metal toxicity. Organic mercury is associated with CNS atrophy and hypoplasia,
      and blindness is a frequent presenting symptom. While not much is known about the
      saint's clinical symptoms (as his ecclestiastical biography focuses on his
      example and miracles), organic mercury poisoning could explain his sudden loss of
      vision, thus possibly making him the first-recorded case of organic mercury
      poisoning in history.

PMID- 27686426
TI  - The BMJ appoints its first China editor.

PMID- 27686427
TI  - Cognitive impairment in depression and its (non-)response to antidepressant
      treatment.

PMID- 27686428
TI  - SAnDReS a Computational Tool for Statistical Analysis of Docking Results and
      Development of Scoring Functions.
AB  - BACKGROUND: Docking allows to predict ligand binding to proteins, since the 3D
      structure for the target is available. Several docking studies have been carried
      out to identify potential ligands for drug targets. Many of these studies
      resulted in the leads that were later developed as drugs. OBJECTIVE: Our goal
      here is to describe the development of an integrated computational tool to assess
      docking accuracy and build new scoring functions to predict ligandbinding
      affinity. METHOD: We carried out docking simulations using MVD program for a data
      set available on CSAR 2014 database (coagulation factor Xa) for which ligand
      binding information and structures are available. These docking results were
      analyzed using SAnDReS available at www.sandres.net. Machine learning methods
      were applied to build new scoring functions and our results were compared with
      previously published benchmarks. RESULTS: Our integrated docking strategy
      generated poses with docking accuracy higher than previously published
      benchmarks. In addition, the new scoring function developed using SAnDReS shows
      better performance than well-established scoring functions such the ones
      available in Autodock, Autodock- Vina, Gold, Glide, and MVD. CONCLUSION: The big
      data generated during docking lacked an integrated computational tool for
      statistical analysis of the influence of structural parameters on docking and
      scoring function performance. Here we describe methods to evaluate docking
      results using SAnDReS, a computational environment for statistical analysis of
      docking results and development of scoring functions. We believe that SAnDReS is
      a computational tool with potential to improve accuracy in docking projects.

PMID- 27686429
TI  - [Importance of clinical reasoning in diagnosis and treatment of
      vertigo/dizziness].

PMID- 27686431
TI  - [Clinical diagnosis and treatment of acute vestibular syndrome].

PMID- 27686430
TI  - [The thinking of clinical diagnosis and treatment of vertigo based on the
      international classification of vestibular disorders].

PMID- 27686432
TI  - [Clinical diagnosis and treatment of episodic vestibular syndrome].

PMID- 27686433
TI  - [Clinical diagnosis and treatment of chronic vestibular syndrome].

PMID- 27686434
TI  - [An analysis of characteristics of nerve conduction in 154 cases of amyotrophic
      lateral sclerosis].
AB  - Objective: To analyze the features of nerve conduction in patients with
      amyotrophic lateral sclerosis (ALS), and explore the correlation between compound
      muscle action potential (CMAP) amplitude and disease duration and revised
      amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). Methods:
      Standard motor and sensory nerve conduction studies were performed in 154
      patients with ALS. The following parameters were collected including CMAP
      amplitude, distal motor latency (DML), motor conduction velocity, sensory
      conduction velocity and sensory nerve action potential amplitude. Regression
      study was done to explore the correlation between CMAP amplitude and disease
      duration and ALSFRS-R. Results: Motor nerve conduction abnormalities were
      presented in a majority of the patients with prolonged DML in the tibial nerve,
      median nerve and ulnar nerve as the most common form (61.06%-81.42%), followed by
      decreased CMAP amplitude (30.12%-53.98%), decreased MCV (12.05%-16.81%) and
      absence of CMAP (2.65%-9.73%). Sensory nerve conduction abnormalities were
      detected in a small proportion of patients and the decreased SCV, decreased SNAP
      amplitude and absence of SNAP in the sural nerve, median nerve and ulnar nerve
      were found in 1.22%-2.73%, 0-1.82% and 0-1.22% patients respectively. No
      correlation was found between CMAP of the common peroneal nerve, tibial nerve,
      median nerve and ulnar nerve and the disease duration (P>0.05), while significant
      positive correlation was established between CMAP amplitude of the median nerve
      and ulnar nerve and ALSFRS-R (r=0.273, P=0.016; r=0.357, P=0.001). Conclusions:
      Motor nerve conduction is abnormal in a majority of ALS patients with prolonged
      DML as the most common form, while abnormal sensory nerve conduction is only
      found in a few of ALS patients. CMAP amplitude of the median nerve and ulnar
      nerve might be of certain clinical value in evaluating the severity of ALS.

PMID- 27686435
TI  - [A clinical study of single subcortical cerebral infarction of middle cerebral
      artery territory].
AB  - Objective: To explore the clinical characteristics of single subcortical cerebral
      infarction of middle cerebral artery (MCA) territory and the possible
      pathogenesis. Methods: A total of 344 cases diagnosed as single subcortical
      cerebral infarction of MCA territory were enrolled in the study and divided into
      the parent artery disease (PAD) group and the non-PAD group according to whether
      the MCA stenosis was presented or not. A total of 312 cases diagnosed as single
      subcortical cerebral infarction of MCA territory were divided into the BAD group
      and the SVD group according to the relationship between the lesion sites and MCA.
      Differences in the clinical and imaging feature were compared between different
      groups. Results: A total of 32 patients were in the PAD group. Compared with the
      non-PAD group, patients in the PAD group were found with higher prevalence of
      asymptomatic cerebral arterial atherosclerosis [93.8%(30/32) vs 57.1%(178/312),
      P<0.001], higher prevalence of branch atheromatous disease[75.0%(24/32) vs
      58.7%(183/312), P=0.072]. A total of 183 patients were in the BAD group. Compared
      with the BAD group, patients in the SVD group were older[(64.7+/-11.2) years vs
      (61.7+/-12.2) years, P=0.031], more with hypertension [65.9%(85/129) vs
      53.0%(97/183), P=0.027] and smoking [41.9%(54/129) vs 57.9%(106/183), P=0.006]
      and more severe leukoaraiosis. Conclusions: Single subcortical cerebral
      infarction of MCA territory has different etiology and pathogenesis. Evidence of
      systemic atherosclerosis should be carefully searched in patients with branch
      atheromatous disease.

PMID- 27686436
TI  - [A clinical analysis of 69 newly diagnosed multiple myeloma patients with renal
      insufficiency].
AB  - Objective: To investigate the efficacy and outcome in newly diagnosed multiple
      myeloma (MM) patients with renal insufficiency using bortezomib- or thalidomide
      based regimens as front line treatment. Method: Sixty-nine newly diagnosed MM
      patients with renal insufficiency were retrospectively analyzed from August 2006
      to August 2014. Results: 1 Among thirty-nine patients with bortezomib based
      regimens (the bortezomib group), the overall response rate (ORR) was 89.7% and
      complete response (CR) plus near CR(nCR) rate was 41.0%. By contrast, among
      thirty patients with thalidomide based regimens (the thalidomide group), the ORR
      was 83.3% and CR+ nCR rate was 26.7%. There was no significant difference of
      either ORR or CR+ nCR rate between bortezomib and thalidomide groups. 2 The
      improvement rate of renal function in bortezomib group and thalidomide group were
      87.2% and 60.0% respectively (P=0.012). The median duration time of renal injury
      was 45 days in 52 patients with renal function improved, which was significantly
      shorter compared with 222 days in 17 patients without improvement (P<0.05). There
      was no difference of median serum creatinine and creatinine clearance rate
      between the two groups.3 The median progression-free survival (PFS) and the
      overall survival (OS) were 18 and 33.5 months, respectively in all patients. The
      three-year and five-year OS rates were 57% and 17%, respectively. The median PFS
      was 19 months in bortezomib group, while it was only 12 months in thalidomide
      group (P=0.023). The median OS were 36.5 months and 25.5 months respectively,
      which was no difference (P=0.285). Conclusions: The newly diagnosed MM patients
      with renal insufficiency could get higher ORR and the longer PFS using bortezomib
      containing regimens as initial therapy. Meanwhile the improvement rate of renal
      function and the living quality in patients with bortezomib are better compared
      with those with thalidomide based treatment.

PMID- 27686437
TI  - [The clinical characteristics of 128 childhood- and adolescent-onset
      hypoparathyroidism in Peking Union Medical College Hospital: a retrospective
      analysis].
AB  - Objective: To study the clinical characteristics of childhood- and adolescent-
      onset hypoparathyroidism. Methods: The clinical data of 128 hypoparathyroidism
      patients with onset before the age of 18 years were collected and analyzed
      retrospectively. Results: The predominant features of the hypoparathyroidism were
      carpopedal spasm (89.3%, 108/121) and seizures (66.1%, 84/127). Intracranial
      calcification was identified in 89.4%(101/113) of the patients. Duration is an
      independent predictive factor (OR=1.483, P=0.011) for intracranial calcification.
      All the patients were treated with calcium and vitamin D or its metabolites.
      Hypercalciuria was associated with serum calcium (P=0.016). Conclusions:
      Carpopedal spasm and seizures were the main manifestations of childhood- and
      adolescent- onset hypoparathyroidism. Calcium and vitamin D or its metabolites
      are effective. Monitoring the concentration of serum and urinary calcium is of
      highly importance for the prevention of hypercalciuria.

PMID- 27686438
TI  - [The clinical feature and microbiological etiology of patients with infective
      endocarditis].
AB  - Objective: To investigate the clinical features, pathogenic distribution and drug
      susceptibility of patients with infective endocarditis (IE). Methods: Clinical
      data of IE patients were collected, who were admitted to Capital Medical
      University Affiliated Beijing Anzhen Hospital from January 2012 to March 2015.
      Results: Three hundred and three IE patients were enrolled with age of (43+/-16)
      years old. Fever (85.5%)and cardiac murmur (62.4%)were the most common clinical
      presentations. Congenital heart diseases was the leading underlying diseases in
      IE patients. Non rheumatic valve diseases (13.5%) followed. Vegetations were
      found in 90.4%(274/303) patients. Streptococcus which accounted for 44.2% was the
      major pathogen of IE. Staphylococcus (28.9%)was the second common pathogen. Gram
      negative bacteria were diversified in categories. Gram-positive cocci were
      consistently sensitive to vancomycin and linezolid. Conclusions: Congenital heart
      disease is the main underlying disease related to IE. Streptococcus is still the
      primary pathogen. Gram-positive cocci keep good sensitivity to vancomycin and
      linezolid.

PMID- 27686439
TI  - [The correlation between optic nerve sheath diameter and volume status in
      patients after cardiac surgery].
AB  - Objective: To investigate the relationship between optic nerve sheath diameter
      (ONSD) and volume status of patients after cardiac surgery. Methods: A total of
      consecutive 56 patients who were treated in Critical Care Unit in Peking Union
      Medical College Hospital after open heart surgery from January to August 2015
      were screened in this study. Central venous pressure (CVP) and 72 h net fluid
      balance were monitored. ONSD and diameter of inferior vena cava (IVC) were
      measured by ultrasound. Results: A total of 44 patients were finally included in
      the study. The postoperative baseline ONSD was (5.31+/-1.96)mm, compared to
      (5.07+/-1.77)mm after 72 h treatment, with DeltaONSD(0.22+/-0.21)mm. Baseline and
      post-treatment at 72 h CVP were (11.98+/-4.09)mmHg and (8.95+/-4.02)mmHg
      respectively. IVC dropped from (19.75+/-4.12)mm to (17.11+/-4.68)mm. DeltaONSD
      and DeltaCVP were significantly correlated (r=0.422, P<0.05), DeltaONSD and net
      fluid balance (NFB) at 72 h were significantly correlated (r=-0.388, P<0.05).
      While DeltaONSD were significantly correlated with DeltaIVC (r=0.423, P<0.05),
      DeltaCVP and DeltaIVC were also significantly correlated (r=0.391, P<0.05).
      Conclusion: The change of ONSD in patients after cardiac surgery is related to
      the change of volume status. Therefore ONSD is helpful to estimate brain edema,
      not only could be a potential index to evaluate volume status, but also be used
      to guide improving prognosis after cardiac surgery.

PMID- 27686440
TI  - [A meta-analysis of low tidal volume on the outcome of adult patients without
      acute respiratory distress syndrome].
AB  - Objective: To evaluate the effects of tidal volume on the survival in adult
      patients without acute respiratory distress syndrome (non-ARDS). Methods: We
      searched relevant clinical randomized controlled trials (RCT) from January 2000
      to December 2015. Meta analyses related to the effects of tidal volume on
      mortality in non-ARDS adults were conducted using the methods recommended by the
      Cochrane Collaboration. Results: A total of nineteen RCTs (n=1 679) were finally
      included. There were 838 patients ventilated with low tidal volume, and the other
      841 patients ventilated with normal tidal volume. The mortality rates were not
      significantly different between low tidal volume group and control group (5.87%
      vs 6.52%; RR=0.9, P=0.58). But respiratory complications were significantly lower
      in low tidal volume group, such as development of acute respiratory distress
      syndrome(RR=0.32, 95% CI 0.16-0.63, P=0.001), pneumonia (RR=0.48, 95%CI 0.29
      0.78, P=0.003), while the incidence of atelectasis was quite comparable between
      two groups (RR=0.78, 95%CI 0.391-1.356, P=0.48). Conclusion: Non-ARDS patients
      ventilated with low tidal volume is associated with a lower risk of pulmonary
      complications, yet clinical outcome, mainly mortality is similar to that of
      patients with regular tidal volume.

PMID- 27686441
TI  - [An analysis and literature review of two cases of autoimmune encephalitis with
      GABAB receptor antibodies].
AB  - Autoimmune encephalitis with GABAB receptor antibodies has been rarely reported.
      Two cases of GABAB receptor antibodies encephalitis were presented here.Epilepsy
      was the onset symptom, followed by declined consciousness and frequent seizures.
      Fever was presented in the whole course of the disease. Myorhythmia of the two
      hands and pilomotor seizures were shown in the later course of the disease. No
      specificity was demonstrated in electroencephalograms and magnetic resonance
      imaging. Sensitive response was shown to the first-line immunotherapy.

PMID- 27686443
TI  - [A novel mutation in SLC40A1 gene in hereditary hemochromatosis in China].

PMID- 27686442
TI  - [The efficacy analysis of interferon combined with imatinib in chronic
      myelogenous leukemia patients with ABL kinase domain mutations].
AB  - To retrospectively analyze the efficacy of interferon plus imatinib (IM) in
      patients with chronic-phase chronic myelogenous leukemia(CML-CP)and ABL kinase
      domain mutations. The mutation rates of ABL kinase region in patients with Sokal
      score low, medium and high risk CML-CP were statistically significant (6.25%,
      9.42% and 47.06%, P<0.05). The response rates of interferon plus IM versus second
      generation TKI in CML-CP with non-T315I ABL kinase domain mutations were
      comparable (61.11% vs 65.52%, P>0.05). When CML-CP patients with ABL kinase
      domain mutations were resistant to TKI or not accessible to second-generation
      TKI, interferon plus IM can be an alternative choice.

PMID- 27686444
TI  - [A case report of sulfasalazine-induced severe neutropenia complicated with
      perianal abscess and septic shock].

PMID- 27686445
TI  - [A case report of Good's syndrome].

PMID- 27686446
TI  - [An overview of hyperglycemic hyperosmolar syndrome].

PMID- 27686447
TI  - [Recent advances of the pathogenesis of achalasia].

PMID- 27686448
TI  - [The progress of application of protective ventilation in patients without acute
      respiratory distress syndrome].

PMID- 27686449
TI  - [Multidisciplinary expert consensus on the prevention and management of bleeding
      in patients with acute coronary syndrome receiving antithrombotic agents].

PMID- 27686450
TI  - Multilevel modelling of somatotype components: the Portuguese sibling study on
      growth, fitness, lifestyle and health.
AB  - BACKGROUND: Somatotype is a complex trait influenced by different genetic and
      environmental factors as well as by other covariates whose effects are still
      unclear. AIMS: To (1) estimate siblings' resemblance in their general somatotype;
      (2) identify sib-pair (brother-brother (BB), sister-sister (SS), brother-sister
      (BS)) similarities in individual somatotype components; (3) examine the degree to
      which between and within variances differ among sib-ships; and (4) investigate
      the effects of physical activity (PA) and family socioeconomic status (SES) on
      these relationships. SUBJECTS AND METHODS: The sample comprises 1058 Portuguese
      siblings (538 females) aged 9-20 years. Somatotype was calculated using the
      Health-Carter method, while PA and SES information was obtained by questionnaire.
      Multi-level modelling was done in SuperMix software. RESULTS: Older subjects
      showed the lowest values for endomorphy and mesomorphy, but the highest values
      for ectomorphy; and more physically active subjects showed the highest values for
      mesomorphy. In general, the familiality of somatotype was moderate (rho = 0.35).
      Same-sex siblings had the strongest resemblance (endomorphy: rhoSS > rhoBB >
      rhoBS; mesomorphy: rhoBB = rhoSS > rhoBS; ectomorphy: rhoBB > rhoSS > rhoBS). For
      the ectomorphy and mesomorphy components, BS pairs showed the highest between sib
      ship variance, but the lowest within sib-ship variance; while for endomorphy BS
      showed the lowest between and within sib-ship variances. CONCLUSIONS: These
      results highlight the significant familial effects on somatotype and the
      complexity of the role of familial resemblance in explaining variance in
      somatotypes.

PMID- 27686452
TI  - MicroRNA-451 sensitizes lung cancer cells to cisplatin through regulation of Mcl
      1.
AB  - As one of the most widely used chemotherapy drugs for lung cancer,
      chemoresistance of cisplatin (DPP) is one of the major hindrances in treatment of
      this malignancy. The microRNAs (miRNAs) have been identified to mediate
      chemotherapy drug resistance. MiR-451 as a tumor suppressor has been evaluated
      its potential effect on the sensitivity of cancer cells to DDP. However, the role
      of miR-451 in regulatory mechanism of chemosensitivity in lung cancer cells is
      still largely unknown. In this study, we first constructed a cisplatin-resistant
      A549 cell line (A549/DPP) accompanied with a decreased expression of miR-451 and
      an increased expression of Mcl-1in the drug resistant cells compared with the
      parental cells. Exogenous expression of miR-451 level in A549/DPP was found to
      sensitize their reaction to the treatment of cisplatin, which coincides with
      reduced expression of Mcl-1. Interestingly, Mcl-1 knockdown in A549/DPP cells
      increased the chemosensitivity to DPP, suggesting the dependence of Mcl-1
      regulation in miR-451 activity. Moreover, miR-451 can restore cisplatin treatment
      response in cisplatin-resistant xenografts in vivo, while Mcl-1 protein levels
      were decreased. Thus, these findings provided that in lung cancer cells, tumor
      suppressor miR-451 enhanced DPP sensitivity via regulation of Mcl-1 expression,
      which could be served as a novel therapeutic target for the treatment of
      chemotherapy resistant in lung cancer.

PMID- 27686451
TI  - Dihydromyricetin suppresses TNF-alpha-induced NF-kappaB activation and target
      gene expression.
AB  - Nuclear factor-kappa B (NF-kappaB) has been reported to play a pivotal role in
      many physiological processes including inflammation, apoptosis, and angiogenesis.
      We discovered a potent natural NF-kappaB inhibitor, dihydromyricetin, from the
      traditional herb Ampelopsis grossedentata, which has a long history of use in
      food and medicine. In this study, we demonstrated the effect of dihydromyricetin
      on NF-kappaB activation in TNF-alpha-induced HeLa cells. Dihydromyricetin was
      found to markedly inhibit the phosphorylation and degradation of the inhibitor of
      NF-kappaB alpha (IkappaBalpha), and subsequent nuclear translocation of p65.
      Dihydromyricetin also has an impact on upstream signaling of IKK through the
      inhibition of expression of adaptor proteins, TNF receptor-associated factor 2
      (TRAF2), and receptor-interacting protein 1 (RIP1). Furthermore, the current
      results reveal that dihydromyricetin led to the downregulation of target genes
      involved in inflammation, proliferation, as well as potentiation of TNF-alpha
      induced apoptosis through suppressing the activation of NF-kappaB. In conclusion,
      our data indicate that dihydromyricetin may be a potentially useful therapeutic
      agent for inflammatory diseases.

PMID- 27686453
TI  - Adenosine monophosphate-activated protein kinase activation and suppression of
      inflammatory response by cell stretching in rabbit synovial fibroblasts.
AB  - Joint mobilization is known to be beneficial in osteoarthritis (OA) patients.
      This study aimed to investigate the effect of stretching on adenosine
      monophosphate-activated protein kinase (AMPK) activity and its role in modulating
      inflammation in rabbit synovial fibroblasts. Uniaxial stretching of isolated
      rabbit synovial fibroblasts for ten min was performed. Stretching-induced AMPK
      activation, its underlying mechanism, and its anti-inflammatory effect were
      investigated using Western blot. Static stretching at 20 % of initial length
      resulted in AMPK activation characterized by expression of phosphorylated AMPK
      and phosphorylated acetyl-Co A carboxylase. AMP-activated protein kinase
      phosphorylation peaked 1 h after stretching and declined toward resting activity.
      Using cell viability assays, static stretching did not appear to cause cellular
      damage. Activation of AMPK involves Ca2+ influx via a mechanosensitive L-type
      Ca2+ channel, which subsequently raises intracellular Ca2+ and activates AMPK via
      Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKKbeta). Interestingly,
      stretching suppressed TNFalpha-induced expression of COX-2, iNOS, and
      phosphorylated NF-kappaB. These effects were prevented by pretreatment with
      compound C, an AMPK inhibitor. These results suggest that mechanical stretching
      suppressed inflammatory responses in synovial fibroblasts via a L-type Ca2+
      channel-CaMKKbeta-AMPK-dependent pathway which may underlie joint mobilization's
      ability to alleviate OA symptoms.

PMID- 27686454
TI  - Chronic intermittent hypoxia affects the cytosolic phospholipase
      A2alpha/cyclooxygenase 2 pathway via beta2-adrenoceptor-mediated ERK/p38
      stimulation.
AB  - Cardiac resistance against acute ischemia/reperfusion (I/R) injury can be
      enhanced by adaptation to chronic intermittent hypoxia (CIH), but the changes at
      the molecular level associated with this adaptation are still not fully explored.
      Phospholipase A2 (PLA2) plays an important role in phospholipid metabolism and
      may contribute to membrane destruction under conditions of energy deprivation
      during I/R. The aim of this study was to determine the effect of CIH (7000 m, 8
      h/day, 5 weeks) on the expression of cytosolic PLA2alpha (cPLA2alpha) and its
      phosphorylated form (p-cPLA2alpha), as well as other related signaling proteins
      in the left ventricular myocardium of adult male Wistar rats. Adaptation to CIH
      increased the total content of cPLA2alpha by 14 % in myocardial homogenate, and
      enhanced the association of p-cPLA2alpha with the nuclear membrane by 85 %. The
      total number of beta-adrenoceptors (beta-ARs) did not change but the beta2/beta1
      ratio markedly increased due to the elevation of beta2-ARs and drop in beta1-ARs.
      In parallel, the amount of adenylyl cyclase decreased by 49 % and Gialpha
      proteins increased by about 50 %. Besides that, cyclooxygenase 2 (COX-2) and
      prostaglandin E2 (PGE2) increased by 36 and 84 %, respectively. In parallel, we
      detected increased phosphorylation of protein kinase Calpha, ERK1/2 and p38 (by
      12, 48 and 19 %, respectively). These data suggest that adaptive changes induced
      in the myocardium by CIH may include activation of cPLA2alpha and COX-2 via beta2
      AR/Gi-mediated stimulation of the ERK/p38 pathway.

PMID- 27686455
TI  - Serum levels of 25-hydroxyvitamin D are associated with periodontal disease.
AB  - OBJECTIVES: Vitamin D plays an essential role in bone metabolism as well as in
      immunity. Hence, it might affect the development and extent of periodontal
      disease. The aim of this study was the assessment of 25-hydroxyvitamin D
      (25(OH)D) status in periodontal disease. MATERIALS AND METHODS: Twenty-nine
      patients with severe periodontal disease and 29 healthy volunteers were recruited
      in this case-control-study. Serum 25(OH)D levels, Periodontal Probing Depth
      (PPD), Clinical Attachment Level (CAL), Bleeding on Probing (BOP), Body Mass
      Index (BMI), and current smoking status and smoking history (packyears) were
      assessed in all participants. Serum 25(OH)D levels were compared between controls
      and cases. Multivariable logistic regression was used to determine the odds ratio
      (OR) and 95 % confidence interval (CI) for periodontal disease in 25(OH)D
      deficient probands. RESULTS: Patients with periodontal disease presented a
      significantly higher proportion of deficient 25(OH)D levels (i.e., <50 nmol/l)
      compared to healthy controls (48 vs. 14 % respectively). The adjusted OR for
      periodontal disease with vitamin D deficiency was 1.5 (95 % CI, 1.13-1.98). No
      correlation between serum 25(OH)D levels and CAL, PPD, and BOP in the group with
      periodontal disease was found. CONCLUSIONS: In this case-control-study 25(OH)D
      deficiency is significantly associated with periodontal disease. CLINICAL
      RELEVANCE: The assessment of vitamin D levels in patients presenting with
      periodontal disease seems advisable, as vitamin D deficiency might be involved in
      the onset and progression of periodontal disease.

PMID- 27686456
TI  - The utilization of spitz-related nomenclature in the histological interpretation
      of cutaneous melanocytic lesions by practicing pathologists: results from the M
      Path study.
AB  - BACKGROUND: Spitz nevi, atypical Spitz tumors and spitzoid melanomas ('spitzoid
      lesions') represent controversial and poorly understood cutaneous melanocytic
      lesions that are difficult to diagnose histologically. It is unknown how these
      terms are used by pathologists. METHODS: We describe use of Spitz-related
      terminology using data from the Melanoma Pathology (M-Path) study database
      comprising pathologists' interpretations of biopsy slides, a nation-wide study
      evaluating practicing US pathologists' (N = 187) diagnoses of melanocytic lesions
      (8976 independent diagnostic assessments on 240 total test cases, with 1 slide
      per case). RESULTS: Most pathologists (90%) used the Spitz-related terminology.
      However, significant variation exists in which specific lesions were diagnosed as
      spitzoid and in the corresponding treatment recommendations. Recommendations
      ranged from 'no further treatment' to 'wide excision of 10 mm or greater' with no
      category capturing more than 50% of responses. For spitzoid melanoma diagnoses,
      90% of pathologists recommended excision with >=10 mm margin. Pathologists report
      less confidence in diagnosing these lesions compared with other melanocytic
      proliferations and are more likely to request second opinions and additional
      clinical information (all p < 0.05). CONCLUSIONS: Spitzoid lesions are often not
      classified in any standardized way, evoke uncertainty in diagnosis by
      pathologists, and elicit variability in treatment recommendations.

PMID- 27686457
TI  - The effect of statins on influenza-like illness morbidity and mortality.
AB  - PURPOSE: The effect of statins on cytokine-mediated inflammatory responses may
      impact on the prognosis of influenza. We assessed whether statin use decreases
      the incidence of adverse influenza-related outcomes. Additionally, we used a new
      user study design to minimize healthy user bias. We further examined the
      possibility of non-causal associations by using unrelated outcomes. METHODS: We
      used the UK Clinical Practice Research Datalink to identify all patients aged 30
      or older diagnosed with influenza-like illness during 1997-2010. Statin users
      were compared with propensity score-matched patients not receiving statins. The
      outcome was hospitalization for influenza or pneumonia or death in the 30 days
      following influenza diagnosis. Logistic regression estimated cumulative incidence
      ratios. RESULTS: The study cohort included 5181 statin users matched to 5181 non
      users. The 30-day incidence of hospitalization or death was 3.5% in statin users
      and 5.2% in non-users, resulting in a 27% lower incidence with statin use
      (cumulative incidence ratio: 0.73, 95%CI: 0.59-0.89). New statin users were less
      protected against our composite outcome. The effect of statins was less
      pronounced among those with respiratory and cardiac disease. Statin use was shown
      to be associated with a non-statistically significant risk reduction of motor
      vehicle accident and burns. CONCLUSION: The attenuation of the effect of statins
      with the new-user design, supporting evidence from the assessment of effect
      modification, and additional sub-analyses evaluating the effect of statins on non
      related outcomes suggest that the beneficial effect of statins on influenza
      related adverse outcomes may be explained by a healthy user bias. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27686462
TI  - The 2016 Assisi Think Tank Meeting on breast cancer: white paper.
AB  - PURPOSE: To identify weak points in daily routine use of radiation therapy (RT)
      for non-metastatic breast cancer patients, particularly when data are lacking or
      equivocal, a "think tank" of experts met in Assisi. METHODS: Before the meeting,
      controversial issues on non-metastatic breast cancer were identified and
      reviewed, and clinical practice investigated by means of an online questionnaire.
      During the 3-day meeting, topics were discussed in-depth with attendees and
      potential sponsors that are involved in breast cancer treatment. RESULTS: Three
      issues were identified as needing further investigation: (1) Regional lymph node
      treatment in early-stage breast cancer; (2) Combined post-mastectomy RT and
      breast reconstruction; (3) RT in patients treated with primary systemic therapy.
      Future research proposals included the following: (1) Participating in
      appropriately selected on-going clinical trials; (2) Designing new randomized
      controlled clinical trials and prospective population cohort studies; (3) Setting
      up large database(s) to generate predictive response models and detect biomarkers
      for tailored loco-regional treatments. CONCLUSIONS: It is hoped that the ATTM
      findings, as described in the present white paper, will stimulate a new
      generation of radiation oncologists to focus on research in these areas, and that
      the white paper will become a tool for multidisciplinary groups to help them
      design research proposals and strategies.

PMID- 27686461
TI  - Characterization of the LBD gene family in Brachypodium: a phylogenetic and
      transcriptional study.
AB  - KEY MESSAGE: An unambiguous nomenclature is proposed for the twenty-eight-member
      LOB domain transcription factor family in Brachypodium . Expression analysis
      provides unique transcript patterns that are characteristic of a wide range of
      organs and plant parts. LOB (lateral organ boundaries)-domain proteins define a
      family of plant-specific transcription factors involved in developmental
      processes from embryogenesis to seed production. They play a crucial role in
      shaping the plant architecture through coordinating cell fate at meristem to
      organ boundaries. Despite their high potential importance, our knowledge of them
      is limited, especially in the case of monocots. In this study, we characterized
      LOB domain protein coding genes (LBDs) of Brachypodium distachyon, a model plant
      for grasses, and present their phylogenetic relationships and an overall spatial
      expression study. In the Brachypodium genome database, 28 LBDs were found and
      then classified based on the presence of highly conserved LOB domain motif. Their
      transcript amounts were measured via quantitative real-time RT-PCR in 37
      different plant parts from root tip to generative organs. Comprehensive
      phylogenetic analysis suggests that there are neither Brachypodium- nor monocot
      specific lineages among LBDs, but there are differences in terms of complexity of
      subclasses between monocots and dicots. Although LBDs in Brachypodium have wide
      variation of tissue-specific expression and relative transcript levels, overall
      expression patterns show similarity to their counterparts in other species. The
      varying transcript profiles we observed support the hypothesis that Brachypodium
      LBDs have diverse but conserved functions in plant organogenesis.

PMID- 27686463
TI  - Increased revision rate with posterior tibial tunnel placement after using the 70
      degree tibial guide in ACL reconstruction.
AB  - PURPOSE: To map knee morphology radiographically in a population with a torn ACL
      and to investigate whether anatomic factors could be related to outcomes after
      ACL reconstruction at mid- to long-term follow-up. Further, we wanted to assess
      tibial tunnel placement after using the 70-degree "anti-impingement" tibial
      tunnel guide and investigate any relation between tunnel placement and revision
      surgery. METHODS: Patients undergoing ACL reconstruction involving the 70-degree
      tibial guide from 2003 to 2008 were included. Two independent investigators
      analysed pre- and post-operative radiographs. Demographic data and information on
      revision surgery were collected from an internal database. Anatomic factors and
      post-operative tibial tunnel placements were investigated as predictors of
      revision. RESULTS: Three-hundred and seventy-seven patients were included in the
      study. A large anatomic variation with significant differences between men and
      women was seen. None of the anatomic factors could be related to a significant
      increase in revision rate. Patients with a posterior tibial tunnel placement,
      defined as 50 % or more posterior on the Amis and Jakob line, did, however, have
      a higher risk of revision surgery compared to patients with an anterior tunnel
      placement (P = 0.03). CONCLUSION: Use of the 70-degree tibial guide did result in
      a high incidence (47 %) of posterior tibial tunnel placements associated with an
      increased rate of revision surgery. The current study was, however, not able to
      identify any anatomic variation that could be related to a higher risk of
      revision surgery. Avoiding graft impingement from the femoral roof in anterior
      tibial tunnel placements is important, but the insight that overly posterior
      tunnel placement can lead to inferior outcome should also be kept in mind when
      performing ACL surgery. LEVEL OF EVIDENCE: IV.

PMID- 27686464
TI  - RNAi prevents and reverses phenotypes induced by mutant human ataxin-1.
AB  - OBJECTIVE: Spinocerebellar ataxia type 1 is an autosomal dominant fatal
      neurodegenerative disease caused by a polyglutamine expansion in the coding
      region of ATXN1. We showed previously that partial suppression of mutant ataxin-1
      (ATXN1) expression, using virally expressed RNAi triggers, could prevent disease
      symptoms in a transgenic mouse model and a knockin mouse model of the disease,
      using a single dose of virus. Here, we set out to test whether RNAi triggers
      targeting ATXN1 could not only prevent, but also reverse disease readouts when
      delivered after symptom onset. METHODS: We administered recombinant adeno
      associated virus (rAAV) expressing miS1, an artificial miRNA targeting human
      ATXN1 mRNA (rAAV.miS1), to a mouse model of spinocerebellar ataxia type 1 (SCA1;
      B05 mice). Viruses were delivered prior to or after symptom onset at multiple
      doses. Control B05 mice were treated with rAAVs expressing a control artificial
      miRNA, or with saline. Animal behavior, molecular phenotypes, neuropathology, and
      magnetic resonance spectroscopy were done on all groups, and data were compared
      to wild-type littermates. RESULTS: We found that SCA1 phenotypes could be
      reversed by partial suppression of human mutant ATXN1 mRNA by rAAV.miS1 when
      delivered after symptom onset. We also identified the therapeutic range of
      rAAV.miS1 that could prevent or reverse disease readouts. INTERPRETATION: SCA1
      disease may be reversible by RNAi therapy, and the doses required for advancing
      this therapy to humans are delineated. Ann Neurol 2016;80:754-765.

PMID- 27686465
TI  - Systematic review to establish absolute standards for technical performance in
      surgery.
AB  - BACKGROUND: Standard setting allows educators to create benchmarks that
      distinguish between those who pass and those who fail an assessment. It can also
      be used to create standards in clinical and simulated procedural skill. The
      objective of this review was to perform a systematic review of the literature
      using absolute standard-setting methodology to create benchmarks in technical
      performance. METHODS: A systematic review was conducted by searching MEDLINE,
      Embase, PsycINFO and the Cochrane Database of Systematic Reviews. Abstracts of
      retrieved studies were reviewed and those meeting the inclusion criteria were
      selected for full-text review. The quality of evidence presented in the included
      studies was assessed using the Medical Education Research Study Quality
      Instrument (MERSQI), where a score of 14 or more of 18 indicates high-quality
      evidence. RESULTS: Of 1809 studies identified, 37 used standard-setting
      methodology for assessment of procedural skill. Of these, 24 used participant
      centred and 13 employed item-centred methods. Thirty studies took place in a
      simulated environment, and seven in a clinical setting. The included studies
      assessed residents (26 of 37), fellows (6 of 37) and staff physicians (17 of 37).
      Seventeen articles achieved a MERSQI score of 14 or more of 18, whereas 20 did
      not meet this mark. CONCLUSION: Absolute standard-setting methodologies can be
      used to establish cut-offs for procedural skill assessments.

PMID- 27686466
TI  - Cytological and biophysical comparative analysis of cell structures at the
      microsporogenesis stage in sterile and fertile Allium species.
AB  - MAIN CONCLUSION: Using a live-cell-imaging approach and autofluorescence-spectral
      imaging, we showed quantitative/qualitative fluctuations of chemical compounds
      within the meiocyte callose wall, providing insight into the molecular basis of
      male sterility in plants from the genus Allium. Allium sativum (garlic) is one of
      the plant species exhibiting male sterility, and the molecular background of this
      phenomenon has never been thoroughly described. This study presents comparative
      analyses of meiotically dividing cells, which revealed inhibition at the
      different microsporogenesis stages in male-sterile A. sativum plants (cultivars
      Harnas and Arkus) and sterile A. ampeloprasum var. ampeloprasum (GHG-L), which is
      phylogenetically related to garlic. Fertile species A. ampeloprasum (leek) was
      used as the control material, because leek is closely related to both garlic and
      GHG-L. To shed more light on the molecular basis of these disturbances,
      autofluorescence-spectral imaging of live cells was used for the assessment of
      the biophysical/biochemical differences in the callose wall, pollen grain
      sporoderm, and the tapetum in the sterile species, in comparison with the fertile
      leek. The use of techniques for live-cell imaging (autofluorescence-spectral
      imaging) allowed the observation of quantitative/qualitative fluctuations of
      autofluorescent chemical compounds within the meiocyte callose wall. The
      biophysical characterisation of the metabolic disturbances in the callose wall
      provides insight into the molecular basis of male sterility in A. sativum. In
      addition, using this method, it was possible for the first time, to determine
      precisely (on the basis of fluctuations of autofluorescence compounds) the
      meiosis stage in which normal microsporogenesis is disturbed, which was not
      visible using light microscopy.

PMID- 27686467
TI  - Stilbene accumulation and expression of stilbene biosynthesis pathway genes in
      wild grapevine Vitis amurensis Rupr.
AB  - MAIN CONCLUSION: We detected and quantified six stilbenes ( cis -piceid, t 
      piceid, t -epsilon-viniferin, cis -epsilon-viniferin, t -resveratrol, and t 
      delta-viniferin) in the leaves, petioles, berry skins, and seeds of wild-growing
      Vitis amurensis . The highest content of stilbenes and expression of stilbene
      biosynthesis genes were in the probes collected in the autumn and after
      ultraviolet elicitation. Stilbenes, including the best-studied stilbene
      resveratrol, are known to display valuable bioactivities and protect plants
      against various pathogens. There is a lack of studies on stilbene quantities and
      spectrum combined with an analysis of the stilbene biosynthesis pathway gene
      expression in Vitaceae species, despite grapevine is an important source of
      stilbenes. This study presents an analysis of stilbene spectrum, stilbene
      content, and expression of stilbene biosynthesis genes both in natural conditions
      and after ultraviolet (UV-C) elicitation in the leaves, petioles, berry skins,
      and seeds of wild-growing Vitis amurensis, a highly stress-tolerant plant
      species. Using HPLC analysis, we detected six main stilbenes: cis-piceid (up to
      0.257 mg/g of dry weight (DW) of plant material), t-piceid (up to 0.055 mg/g DW),
      t-epsilon-viniferin (up to 0.122 mg/g DW), cis-epsilon-viniferin (up to 0.031
      mg/g DW), t-resveratrol (from 0.004 to 0.121 mg/g DW), and t-delta-viniferin (up
      to 0.019 mg/g DW). The stilbenes were actively synthesized in the leaves (total
      stilbenes 0.39 mg/g DW) and berry skins (total stilbenes 0.249 mg/g DW) of V.
      amurensis collected in the autumn. qRT-PCR revealed that the stilbene synthase
      (STS), resveratrol O-glucosyltransferase (Glu1), and polyphenol oxidase (PPO1)
      genes were actively expressed in the analyzed tissues. The resveratrol
      methyltransferase (Romt1) gene, which is known to catalyze biosynthesis of
      pterostilbene, was also expressed, but no pterostilbene has been detected in V.
      amurensis. The content of all detected stilbenes and expression of stilbene
      biosynthesis genes increased after UV-C treatment, except for Romt1. The data are
      important for understanding the stilbene biosynthesis in grapevine.

PMID- 27686468
TI  - Diagnostic utility of a computer-aided diagnosis system for whole-body bone
      scintigraphy to detect bone metastasis in breast cancer patients.
AB  - OBJECTIVE: To compare the diagnostic ability of planar images (PI) and images
      obtained by a computer-aided diagnosis (CAD) system (Viewer for Standardized Bone
      Scintigraphies; VSBONE) of whole-body bone scintigraphy for detecting bone
      metastases in breast cancer patients. METHODS: 81 women (median: 56 years; range:
      32-79) with a history of breast cancer were included in this study. They
      underwent whole-body bone scintigraphy after intravenous injection of 740 MBq
      technetium-99m hydroxymethylene diphosphonate. A total of 1066 bones (162 regions
      of the skull, 657 regions of the spine and pelvis, 223 regions of the sternum and
      rib, 18 regions of the upper extremities, and 6 regions of the lower extremities)
      were analyzed. The PI alone, VSBONE images alone, and both PI and VSBONE images
      (PI + VSBONE) were interpreted independently by two radiologists to diagnose bone
      metastases, which were then confirmed by magnetic resonance imaging. The
      sensitivity and specificity for each modality were analyzed using Fisher's exact
      and McNemar tests. Inter-reviewer agreement was evaluated using a kappa
      statistic. RESULTS: Bone metastases were confirmed in 43 patients with 442
      positive lesions. The average sensitivity of PI, VSBONE images, and PI + VSBONE
      images was 40.8, 50.2, and 61.8 %, respectively. The average specificity was
      97.8, 97.5, and 97.6 %, respectively. The kappa scores were 0.62 for PI, 0.69 for
      VSBONE, and 0.77 for PI + VSBONE. CONCLUSIONS: VSBONE was superior to PI in
      regard to sensitivity for detecting bone metastases in breast cancer patients.
      However, an improved CAD system is required to decrease the number of false
      negative results.

PMID- 27686469
TI  - Intratumoral heterogeneity of 18F-FLT uptake predicts proliferation and survival
      in patients with newly diagnosed gliomas.
AB  - BACKGROUND: The nucleoside analog 3'-deoxy-3'-18F-fluorothymidine (FLT) has been
      investigated for evaluating tumor proliferating activity in brain tumors. We
      evaluated FLT uptake heterogeneity using textural features from the histogram
      analysis in patients with newly diagnosed gliomas and examined correlation of the
      results with proliferative activity and patient prognosis, in comparison with the
      conventional PET parameters. METHODS: FLT PET was investigated in 37 patients
      with newly diagnosed gliomas. The conventional parameters [tumor-to-contralateral
      normal brain tissue (T/N) ratio and metabolic tumor volume (MTV)] and textural
      parameters (standard deviation, skewness, kurtosis, entropy, and uniformity) were
      derived from FLT PET images. Linear regression analysis was used to compare PET
      parameters and the proliferative activity as indicated by the Ki-67 index. The
      associations between parameters and overall survival (OS) were tested by Cox
      regression analysis. RESULTS: Median OS was 662 days. For the conventional
      parameters, linear regression analysis indicated a significant correlation
      between T/N ratio and Ki-67 index (p = 0.02) and MTV and Ki-67 index (p = 0.02).
      Among textural parameters, linear regression analysis indicated a significant
      correlation for kurtosis (p = 0.003), entropy (p < 0.001), and uniformity (p <
      0.001) as compared to Ki-67 index, exceeding those of the conventional
      parameters. The results of univariate analysis suggested that skewness and
      kurtosis were associated with OS (p = 0.03 and 0.02, respectively). Mean survival
      for patients with skewness values less than 0.65 was 1462 days, compared with 917
      days for those with values greater than 0.65 (p = 0.02). Mean survival for
      patients with kurtosis values less than 6.16 was 1616 days, compared with 882
      days for those with values greater than 6.16 (p = 0.006). CONCLUSIONS: Based on
      the results of this preliminary study in a small patient population, textural
      features reflecting heterogeneity on FLT PET images seem to be useful for the
      assessment of proliferation and for the potential prediction of survival in newly
      diagnosed gliomas.

PMID- 27686470
TI  - Risk Factors for Return to the Operating Room after Resident-Performed Cataract
      Surgery.
AB  - OBJECTIVE: Investigate risk factors for unplanned return to the operating room
      after resident-performed cataract surgery. DESIGN: Retrospective case-control
      study. SETTING: Institutional. METHODS: Study population: All patients with
      reoperation within 90 days of resident-performed phacoemulsification were matched
      to four control eyes which had surgery within 30 days of the reoperation at the
      same institution. OBSERVATION PROCEDURE: Billing codes were used to identify all
      patients who underwent resident-performed intended phacoemulsification with
      intraocular lens placement from January 2005 to December 2010. MAIN OUTCOME
      MEASURES: Investigated risk factors for reoperation included cataract
      characteristics and preexisting ocular co-morbidities, including diabetic
      retinopathy, retinal detachment history, glaucoma, corneal pathology, and
      uveitis. Additional preoperative risk factors studied included resident training
      year, history of tamsulosin use, phacodonesis, pupillary dilation, presence of
      pseudoexfoliation, myopia, history of trauma, visual acuity, and monocular
      status. Intraoperative variables were the use of iris expansion devices, use of
      capsular stain, attending type, incision type, use of sutures, vitreous loss,
      anesthesia type, and phacoemulsification technique. RESULTS: There were 67
      returns to the operating room (i.e., cases) over five years that were assigned to
      268 control eyes. In preoperative multivariate analysis, phacoemulsification done
      by a first- or second-year resident (OR 3.2, 95% CI: 1.7-6.0, p < 0.001) was
      associated with an increased risk of reoperation. In postoperative multivariate
      analysis, only the use of the divide-and-conquer technique (OR 4.0, 95% CI:1.7
      9.2, p = 0.001) was associated with an increased risk of reoperation.
      CONCLUSIONS: Phacoemulsification done by a junior resident or using the divide
      and-conquer technique had the highest risk of reoperation.

PMID- 27686471
TI  - Targeted de-escalation rounds may effectively and safely reduce meropenem use.
AB  - OBJECTIVE: Use of meropenem in our hospital has doubled in recent years. An audit
      in 2013 showed that although initiation of therapy with meropenem was generally
      appropriate, therapy was rarely subsequently reviewed and de-escalated where
      appropriate. Therefore, a structured stewardship initiative focussed on meropenem
      de-escalation was developed. METHODS: A local guideline for review and de
      escalation of meropenem was developed and approved by the Antimicrobial
      Stewardship Team. The guideline outlined clinical and microbiological criteria
      which when met should lead to recommendation for meropenem de-escalation.
      Implementation of the guideline was piloted for a period of 4 weeks by a
      consultant microbiologist and an antimicrobial pharmacist. Days of meropenem use
      and crude mortality in those in whom de-escalation was implemented were compared
      with those where de-escalation was not recommended or was recommended but not
      implemented. RESULTS: Thirty-three patients were reviewed. Overall, a
      recommendation to de-escalate from meropenem to a specified alternative
      antibiotic was made for 18 (55 %) patients. This advice was followed for 12 (36
      %) patients. The median days of meropenem use in patients where meropenem was de
      escalated was 4.5 days (range 2-19) compared with 14 days (range 6-84) where de
      escalation was not recommended or the recommendation was not implemented. There
      was no statistically significant difference in crude mortality between patients
      de-escalated from meropenem and those where meropenem was continued. CONCLUSION:
      This pilot study suggests that targeted carbapenem de-escalation stewardship
      activity based on pre-determined criteria, while labour intensive, can
      effectively and safely reduce meropenem use in the acute hospital setting.

PMID- 27686472
TI  - Is intraoperative frozen section analysis of the proximal bile ducts in hilar
      cholangiocarcinoma of limited value?
AB  - Mantel et al. showed that the use of intraoperative frozen section analysis of
      the proximal bile ducts has a limited contribution in obtaining secondary R0
      resections and final resection status had no impact on recurrence rate in hilar
      cholangiocarcinoma. However, the accuracy, sensitivity, and specificity of
      intraoperative frozen section analysis were determined by the specific pathologic
      features of the tumor and the different experienced pathologists in different
      pathology laboratories. It has been demonstrated that tumor-free resection margin
      (R0) is the most prognostic factor for survival, as well as the only factor that
      can be modified by the surgeons. Ribero et al. reported an improvement in
      prognosis was found in the secondary R0 group. As the conclusion given by Mantel
      et al. and Shingu et al., which is contrary to Ribero et al. Before the real role
      of intraoperative frozen section in the analysis of the margin of proximal bile
      ducts in treating hilar cholangiocarcinoma is concluded, further studies are
      still needed.

PMID- 27686473
TI  - The effect of the order in which episodic autobiographical memories versus
      autobiographical knowledge are shared on feelings of closeness.
AB  - Autobiographical memories (AMs) can be used to create and maintain closeness with
      others [Alea, N., & Bluck, S. (2003). Why are you telling me that? A conceptual
      model of the social function of autobiographical memory. Memory, 11(2), 165-178].
      However, the differential effects of memory specificity are not well established.
      Two studies with 148 participants tested whether the order in which
      autobiographical knowledge (AK) and specific episodic AM (EAM) are shared affects
      feelings of closeness. Participants read two memories hypothetically shared by
      each of four strangers. The strangers first shared either AK or an EAM, and then
      shared either AK or an EAM. Participants were randomly assigned to read either
      positive or negative AMs from the strangers. Findings suggest that people feel
      closer to those who share positive AMs in the same way they construct memories:
      starting with general and moving to specific.

PMID- 27686474
TI  - Impurities in Drug Products and Active Pharmaceutical Ingredients.
AB  - Analytical methods should be selective and fast. In modern times, scientists
      strive to meet the criteria of green chemistry, so they choose analytical
      procedures that are as short as possible and use the least toxic solvents. It is
      quite obvious that the products intended for human consumption should be
      characterized as completely as possible. The safety of a drug is dependent mainly
      on the impurities that it contains. High pressure liquid chromatography and ultra
      high pressure liquid chromatography have been proposed as the main techniques for
      forced degradation and impurity profiling. The aim of this article was to
      characterize the relevant classification of drug impurities and to review the
      methods of impurities determination for atorvastatin (ATV) and duloxetine (DLX)
      (both in active pharmaceutical ingredients and in different dosage forms). These
      drugs have an impact on two systems of the human body: cardiac and nervous.
      Simple characteristics of ATV and DLX, their properties and specificity of action
      on the human body, are also included in this review. The analyzed pharmaceuticals
      ATV (brand name Lipiron) and DLX (brand name Cymbalta)-were selected for this
      study based on annual rankings prepared by Information Medical Statistics.

PMID- 27686475
TI  - An extremely rare case of tubo-ovarian abscesses involving corynebacterium
      striatum as causative agent.
AB  - BACKGROUND: We present an extremely rare case of tubo-ovarian abscesses involving
      Corynebacterium striatum (C. striatum) as causative agent in a 53-year-old woman.
      CASE PRESENTATION: The patient presented with stomach pain, chills, and nausea.
      Her medical history included poorly controlled psoriasis vulgaris and diabetes.
      Laboratory and imaging findings led to diagnosis of septic shock due to tubo
      ovarian abscesses. She was treated with antibiotic therapy and surgery to remove
      the left adnexa. Various cultures detected Prevotella spp. and C. striatum. We
      concluded that C. striatum from skin contaminated by psoriasis vulgaris had
      caused the tubo-ovarian abscesses by way of ascending infection. CONCLUSIONS:
      This may be the first known case of tubo-ovarian abscesses due to C. striatum. In
      patients whose skin has been weakened by psoriasis vulgaris or other infections,
      Corynebacterium should be considered as causative microorganisms, and antibiotic
      therapy including vancomycin should be administered.

PMID- 27686476
TI  - The effect of oral positioning on the hypopharyngeal airway.
AB  - OBJECTIVES: It is generally assumed that mouth opening decreases the
      hypopharyngeal cross-sectional area (HA) and that tongue protrusion (TP)
      increases the HA. We hypothesize that a substantial number of patients do not
      exhibit this expected pattern. STUDY DESIGN: Prospective cohort conducted at a
      tertiary academic center. METHODS: With a flexible fiberoptic scope in position,
      the hypopharyngeal airway was visualized and assessed in 189 patients with the
      mouth closed. Patients were then asked to open the mouth with the tongue in
      neutral position (MOTN) to determine the effect on the airway. The same
      methodology was used to compare the airway with the MOTN versus TP. Basic
      demographics, including age, gender, body mass index, and presence and severity
      of obstructive sleep apnea (OSA), were collected. Student t test, Mantel-Haenszel
      chi-square, and Cochran-Armitage analyses were assessed for significant
      relationships and trends with oral positions. RESULTS: Although mean HA decreased
      with MOTN (P < 0.0001), 33% of patients exhibited an increase in HA. Similarly,
      mean HA increased with TP (P = 0.0018); however, 38% of patients demonstrated a
      decrease in HA. There was no significant relationship in HA between OSA and non
      OSA patients. For those with OSA, increasing severity trended toward a higher
      incidence of smaller HA with TP (P = 0.038). CONCLUSION: The airway is typically
      most obstructed with mouth opening (MOTN) and most patent with tongue protrusion
      (TP). Nevertheless, hypopharyngeal changes with MOTN and TP followed a
      paradoxical pattern in one-third of our population. This may have implications in
      patient selection for targeted OSA treatment. LEVEL OF EVIDENCE: 4. Laryngoscope,
      127:1471-1475, 2017.

PMID- 27686477
TI  - Occupational identity of adolescents with ADHD: A mixed methods study.
AB  - BACKGROUND: Occupational identity (OI) is shaped by occupational experiences over
      time and has been studied among individuals with a variety of health conditions.
      Adolescents with ADHD face numerous challenges in their occupational performance
      that may threaten their OI. OBJECTIVE: This study sought to compare the
      occupational identities of adolescents with and without ADHD and to gain a deeper
      understanding of the characteristics of OI among adolescents with ADHD. METHODS:
      Sixty-four adolescents with (n = 21) and without ADHD (n = 43) were interviewed
      using the Occupational Performance History Interview (OPHI-II). A mixed
      methodology was applied, using quantitative and subsequent qualitative content
      analyses of 10 interviews, with a directed approach. RESULTS: OPHI-II OI interval
      scores and 7/11 items of the OI scale were significantly lower in the ADHD group
      compared to controls. In the qualitative content analyses, three major themes
      were found: (i) the meaning of success in academic participation, (ii) the
      consequences of not succeeding in academic participation and (iii) self
      explanations for not succeeding in academic participation. CONCLUSION: Findings
      demonstrate the presence of OI challenges among adolescents with ADHD.
      Occupational therapy intervention may be needed in order to promote occupational
      adaptation.

PMID- 27686478
TI  - Quassinoids isolated from Brucea javanica inhibit pepper mottle virus in pepper.
AB  - A green fluorescent protein (GFP)-tagged pepper mottle virus (PepMoV) based leaf
      disc method and systemic host method were developed to identify antiviral agents.
      Preliminary experiments using a PepMoV-GFP based leaf-disc method led to the
      isolation of five quassinoids, including brusatol (1), bruceantin (2), brucein A
      (3), bruceantinol (4), and brucein B (5), from the CH3OH extract of Brucea
      javanica. All isolated compounds exhibited inactivation effects in systemic host
      plants, and compounds 3 and 4 were potent, with a minimum inhibitory
      concentration of 10MUM. Furthermore, compound 3 was found to have a protective
      effect at the tested concentration of 40MUM.

PMID- 27686479
TI  - Tumor-homing effect of human mesenchymal stem cells in a TH-MYCN mouse model of
      neuroblastoma.
AB  - BACKGROUND: Human mesenchymal stem cells (hMSCs) are multipotent stem-like cells
      that are reported to have tumor-suppression effects and migration ability toward
      damaged tissues or tumors. The aim of this study was to analyze the tumor-homing
      ability of hMSCs and antitumor potency in a transgenic TH-MYCN mouse model of
      neuroblastoma (NB). METHODS: hMSCs (3*106) labeled with DiR, a lipophilic near
      infrared dye, were intraperitoneally (i.p.) or intravenously (i.v.) administered
      to the TH-MYCN mice. hMSC in vivo kinetics were assayed using the IVIS(r) imaging
      system for 24h after injection. Immunohistochemistry using human CD90 antibody
      was also performed to confirm the location of hMSCs in various organs and tumors.
      Furthermore, the survival curve of TH-MYCN mice treated with hMSCs was compared
      to a control group administered PBS. RESULTS: i.p. hMSCs were recognized in the
      tumors of TH-MYCN mice by IVIS. hMSCs were also located inside the tumor tissue.
      Conversely, most of the i.v. hMSCs were captured by the lungs, and migration into
      the tumors was not noted. There was no significant difference in the survival
      between the hMSC and control groups. CONCLUSION: The present study suggested that
      hMSCs may be potential tumor-specific therapeutic delivery vehicles in NB
      according to their homing potential to tumors.

PMID- 27686480
TI  - Fine clinical differences between patients with multifocal and diffuse hepatic
      hemangiomas.
AB  - BACKGROUND: It has been reported that multifocal and diffuse hepatic hemangiomas
      are true infantile hemangiomas for which a continuum probably exists. We
      determined the similarities and fine differences between the two types of
      hemangioma and identified the multifocal subgroup of type, which needs timely
      treatment. MATERIAL AND METHODS: Twenty-four patients (4 males and 20 females;
      age 114+/-142days) with multifocal or diffuse hepatic hemangiomas who were
      treated between January 2000 and June 2015 were studied. For the multifocal type,
      patients were divided into countable (MC) and uncountable (MU) subgroups. The
      medical data were analyzed retrospectively. RESULTS: The clinical presentations
      included hepatomegaly (n=11), dyspnea (n=7), heart failure (n=9), hypothyroidism
      (n=6), and anemia (n=1). There were 19 and 5 patients with multifocal and diffuse
      types, and 6 and 13 patients in the MC and MU groups, respectively. There were
      significant differences between the multifocal and diffuse types with respect to
      hepatomegaly, heart failure, dyspnea, and hypothyroidism. However, there was no
      difference between the MU group and the diffuse type except for hypothyroidism.
      Observation was commonly recommended for patients with the multifocal type, and
      their survival rate was clearly higher than for patients with the diffuse type.
      Both the MU and diffuse-type groups needed treatment, unlike MC patients. The
      complete remission rate was higher in the MC group than in the MU and diffuse
      type groups. Patients with the diffuse type were more likely to die. CONCLUSIONS:
      Patients with diffuse-type hepatic hemangioma are at high risk and need active
      treatment. The MU group for the multifocal type is unique and has high
      similarities to the diffuse type with respect to clinical presentation and
      treatment, which suggests that a continuum of the disease phenotypes exists.
      LEVEL OF EVIDENCE: Case-control study, level III.

PMID- 27686481
TI  - The association of insurance status on the probability of transfer for pediatric
      trauma patients.
AB  - BACKGROUND/PURPOSE: The purpose of this study was to evaluate the association of
      insurance status on the probability of transfer of pediatric trauma patients to
      level I/II centers after initial evaluation at lower level centers. METHODS: A
      retrospective review of all pediatric trauma patients (age<16years) registered in
      the 2007-2012 National Trauma Data Bank was performed. Multiple regression
      techniques controlling for clustering at the hospital level were used to
      determine the impact of insurance status on the probability of transfer to level
      I/II trauma centers. RESULTS: Of 38,205 patients, 33% of patients (12,432) were
      transferred from lower level centers to level I/II trauma centers. Adjusting for
      demographics and injury characteristics, children with no insurance had a higher
      likelihood of transfer than children with private insurance. Children with public
      or unknown insurance status were no more likely to be transferred than privately
      insured children. There were no variable interactions with insurance status.
      CONCLUSIONS: Among pediatric trauma patients, lack of insurance is an independent
      predictor for transfer to a major trauma center. While burns, severely injured,
      and younger patients remain the most likely to be transferred, these findings
      suggest a triage bias influenced by insurance status. Additional policies may be
      needed to avoid unnecessary transfer of uninsured pediatric trauma patients.
      LEVEL OF EVIDENCE: Case-control study, level III.

PMID- 27686482
TI  - MEK inhibitors as a novel therapy for neuroblastoma: Their in vitro effects and
      predicting their efficacy.
AB  - BACKGROUND: A recent study reported that relapsed neuroblastomas had frequent RAS
      ERK pathway mutations. We herein investigated the effects and pathways of MEK
      inhibitors, which inhibit the RAS-ERK pathway, as a new molecular-targeted
      therapy for refractory neuroblastomas. METHOD: Five neuroblastoma cell lines were
      treated with trametinib (MEK inhibitor) or CH5126766 (RAF/MEK inhibitor). Growth
      inhibition was analyzed using a cell viability assay. ERK phosphorylation and the
      MYCN expression were analyzed by immunoblotting or immunohistochemistry. RAS/RAF
      mutations were identified by direct sequencing or through the COSMIC database.
      RESULTS: Both MEK inhibitors showed growth inhibition effects on cells with ERK
      phosphorylation, but almost no effect on cells without. In immunoblotting
      analyses, ERK phosphorylation and MYCN expression were suppressed in ERK active
      cells by these drugs. Furthermore, phosphorylated-ERK immunohistochemistry
      corresponded to the drug responses. Regarding the relationship between RAS/Raf
      mutations and ERK phosphorylation, ERK was phosphorylated in one cell line (NLF)
      without RAS/Raf mutations. CONCLUSION: MEK inhibitors are a promising molecular
      targeted therapeutic option for ERK active neuroblastomas. The efficacy of MEK
      inhibitors corresponds to ERK phosphorylation, while RAS/RAF mutations are not
      always detected in drug-sensitive cells. Phosphorylated-ERK immunohistochemistry
      is thus a useful method to analyze ERK activity and predict the therapeutic
      effects of MEK inhibitors.

PMID- 27686483
TI  - Treatment outcomes in pediatric melanoma-Are there benefits to specialized care?
AB  - PURPOSE: The purpose of this study was to evaluate the impact of hospital
      specialization on survival in pediatric melanoma. METHODS: We reviewed all
      patients under 18years old with cutaneous melanoma evaluated at MD Anderson
      Cancer Center, a National Cancer Institute (NCI)-designated center, from 2000 to
      2014. We compared overall survival (OS) and disease-free survival (DFS) between
      patients who underwent all treatments at MDACC (Group A, n=146) and those who
      underwent initial surgical treatment at a non-NCI center (Group B, n=58). Kaplan
      Meier survival curves were compared using the log-rank test. RESULTS: Group A
      patients had significantly better OS and DFS (both p<0.001). Five-year OS was 97%
      (95% CI 92%-99%) in Group A versus 88% (95% CI 74%-94%) in Group B. Group
      survival differences were most notable in Stage 3 and 4 patients. Group A
      patients presenting with stage III or IV disease had a 5-year OS rate of 91.2%
      (95% CI 75.1%-97.1%) compared to 80.8% (95% CI 59.8%-91.5%) in Group B. The DFS
      rate was 94.4% (95% CI 88.5%-97.3%) in Group A versus 77.2% (95% CI 62.5%-86.7%)
      in Group B. CONCLUSION: Surgical treatment at a comprehensive cancer center may
      improve outcomes for pediatric melanoma especially for patients presenting with
      later stage disease. LEVEL OF EVIDENCE: Case-control study: Level III.

PMID- 27686484
TI  - Reinforcing the ventral penile shaft with pedicled fat/connective tissues before
      urethroplasty lowers the risk for post-urethroplasty complications in
      hypospadias.
AB  - PURPOSE: CHARGE is our technique for reinforcing the ventral penile shaft with
      pedicled pericordal/scrotal fat, pedicled perimeatal connective tissue, or a
      combination of these at the time of initial hypospadias surgery. Such pedicled
      grafts "charge" poorly developed urethral plates and thin ventral foreskin prior
      to urethroplasty to improve compromised vascular perfusion that could prevent
      post-urethroplasty complications (post-UPC). METHODS: We reviewed post-UPC in 179
      staged hypospadias repair patients (1997-2015). CHARGE, adopted routinely in 2010
      was used in 39 patients (C-group), not indicated in 7 because ventral connective
      tissue was thick, and not used in 133 (NC-group). Initial hypospadias surgery
      included foreskin degloving with or without chordectomy, dorsal plication, tunica
      albuginea incision, or a combination of these. RESULTS: Subject demographics were
      similar. NC had significantly more post-UPC than C (25 versus 0; p<.01)
      comprising stenosis (n=14), fistula (n=7), diverticulum (n=2), and wound
      infection (n=2) that developed after a mean of 0.7+/-0.2years (range: 1day
      2.8years). Extra time taken for CHARGE was less than 15minutes in all cases. Mean
      follow-up after urethroplasty (years) was significantly shorter in C (1.5+/-1.0
      versus 5.7+/-3.8) (p<.01), but almost double the time taken to develop post-UPC.
      CONCLUSION: CHARGE would appear to prevent post-UPC. LEVEL OF EVIDENCE:
      Retrospective Comparative Study - Level III.

PMID- 27686485
TI  - Clinicoradiologic Correlations of Cerebral Microbleeds in Advanced Age.
AB  - BACKGROUND AND PURPOSE: The presence of cerebral microbleeds has been associated
      with dementia and cognitive decline, although studies report conflicting results.
      Our aim was to determine the potential role of the presence and location of
      cerebral microbleeds in early stages of cognitive decline. MATERIALS AND METHODS:
      Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively
      intact community-dwelling controls and 72 subjects with mild cognitive impairment
      were analyzed with respect to the presence and distribution of cerebral
      microbleeds. A neuropsychological follow-up of controls was performed at 18
      months post inclusion and identified cases with subtle cognitive deficits were
      referred to as controls with a deteriorating condition. Group differences in
      radiologic parameters were studied by using nonparametric tests, 1-way analysis
      of variance, and Spearman correlation coefficients. RESULTS: Cerebral microbleed
      prevalence was similar in subjects with mild cognitive impairment and controls
      with stable and cognitively deteriorating conditions (25%-31.9%). In all
      diagnostic groups, lobar cerebral microbleeds were more common. They occurred in
      20.1% of all cases compared with 6.5% of cases with deep cerebral microbleeds.
      None of the investigated variables (age, sex, microbleed number, location and
      depth, baseline Mini-Mental State Examination score, and the Fazekas score) were
      significantly associated with cognitive deterioration with the exception of
      education of >12 years showing a slight but significant protective effect (OR,
      0.44; 95% CI, 0.22-0.92; P = .028). The Mini-Mental State Examination and the
      Buschke total score were correlated with neither the total number nor lobar
      versus-deep location of cerebral microbleeds. CONCLUSIONS: Cerebral microbleed
      presence, location, and severity are not related to the early stages of cognitive
      decline in advanced age.

PMID- 27686486
TI  - Genetics of Frontotemporal Dementia.

PMID- 27686487
TI  - Hippocampal and Deep Gray Matter Nuclei Atrophy Is Relevant for Explaining
      Cognitive Impairment in MS: A Multicenter Study.
AB  - BACKGROUND AND PURPOSE: The structural MR imaging correlates of cognitive
      impairment in multiple sclerosis are still debated. This study assessed lesional
      and atrophy measures of white matter and gray matter involvement in patients with
      MS acquired in 7 European sites to identify the MR imaging variables most closely
      associated with cognitive dysfunction. MATERIALS AND METHODS: Brain dual-echo, 3D
      T1-weighted, and double inversion recovery scans were acquired at 3T from 62
      patients with relapsing-remitting MS and 65 controls. Patients with at least 2
      neuropsychological tests with abnormal findings were considered cognitively
      impaired. Focal WM and cortical lesions were identified, and volumetric measures
      from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age- and
      site-adjusted models were used to compare lesion and volumetric MR imaging
      variables between patients with MS who were cognitively impaired and cognitively
      preserved. A multivariate analysis identified MR imaging variables associated
      with cognitive scores and disability. RESULTS: Twenty-three patients (38%) were
      cognitively impaired. Compared with those with who were cognitively preserved,
      patients with MS with cognitive impairment had higher T2 and T1 lesion volumes
      and a trend toward a higher number of cortical lesions. Significant brain,
      cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients
      with MS with cognitive impairment versus those who were cognitively preserved.
      Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive
      impairment, while WM atrophy was the best predictor of disability. CONCLUSIONS:
      Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive
      impairment in MS. These MR imaging measures could be applied in a multicenter
      context, with cognition as clinical outcome.

PMID- 27686488
TI  - Flow Conditions in the Intracranial Aneurysm Lumen Are Associated with
      Inflammation and Degenerative Changes of the Aneurysm Wall.
AB  - BACKGROUND AND PURPOSE: Saccular intracranial aneurysm is a common disease that
      may cause devastating intracranial hemorrhage. Hemodynamics, wall remodeling, and
      wall inflammation have been associated with saccular intracranial aneurysm
      rupture. We investigated how saccular intracranial aneurysm hemodynamics is
      associated with wall remodeling and inflammation of the saccular intracranial
      aneurysm wall. MATERIALS AND METHODS: Tissue samples resected during a saccular
      intracranial aneurysm operation (11 unruptured, 9 ruptured) were studied with
      histology and immunohistochemistry. Patient-specific computational models of
      hemodynamics were created from preoperative CT angiographies. RESULTS: More
      stable and less complex flows were associated with thick, hyperplastic saccular
      intracranial aneurysm walls, while slower flows with more diffuse inflow were
      associated with degenerated and decellularized saccular intracranial aneurysm
      walls. Wall degeneration (P = .041) and rupture were associated with increased
      inflammation (CD45+, P = .031). High wall shear stress (P = .018), higher
      vorticity (P = .046), higher viscous dissipation (P = .046), and high shear rate
      (P = .046) were associated with increased inflammation. Inflammation was also
      associated with lack of an intact endothelium (P = .034) and the presence of
      organized luminal thrombosis (P = .018), though overall organized thrombosis was
      associated with low minimum wall shear stress (P = .034) and not with the flow
      conditions associated with inflammation. CONCLUSIONS: Flow conditions in the
      saccular intracranial aneurysm are associated with wall remodeling. Inflammation,
      which is associated with degenerative wall remodeling and rupture, is related to
      high flow activity, including elevated wall shear stress. Endothelial injury may
      be a mechanism by which flow induces inflammation in the saccular intracranial
      aneurysm wall. Hemodynamic simulations might prove useful in identifying saccular
      intracranial aneurysms at risk of developing inflammation, a potential biomarker
      for rupture.

PMID- 27686490
TI  - Abstracts of the Meeting of the Belgian Society of Internal Medicine February
      14,1998.

PMID- 27686489
TI  - Comparison of Quantitative Cerebral Blood Flow Measurements Performed by Bookend
      Dynamic Susceptibility Contrast and Arterial Spin-Labeling MRI in Relapsing
      Remitting Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: Quantitative CBF usage as a biomarker for cognitive
      impairment and disease progression in MS is potentially a powerful tool for
      longitudinal patient monitoring. Dynamic susceptibility contrast perfusion with
      bookend T1-calibration (bookend technique) and pseudocontinuous arterial spin
      labeling have recently been used for CBF quantification in relapsing-remitting
      MS. The noninvasive nature of pseudocontinuous arterial spin-labeling is
      advantageous over gadolinium-based techniques, but correlation between the
      techniques is not well-established in the context of MS. MATERIALS AND METHODS:
      We compared pseudocontinuous arterial spin-labeling CBF with the bookend
      technique in a prospective cohort of 19 healthy controls, 19 subjects with
      relapsing-remitting MS without cognitive impairment, and 20 subjects with
      relapsing-remitting MS with cognitive impairment on a voxelwise and Brodmann
      region basis. The linear Pearson correlation, SNR, and coefficient of variation
      were quantified. RESULTS: Voxelwise paired t tests revealed no significant CBF
      differences between techniques after normalization of global mean intensities.
      The highest Pearson correlations were observed in deep GM structures (average r =
      0.71 for the basal ganglia and r = 0.65 for the thalamus) but remained robust for
      cortical GM, WM, and white matter lesions (average r = 0.51, 0.53, 0.54,
      respectively). Lower Pearson correlations were observed for cortical lesions
      (average r = 0.23). Brodmann region correlations were significant for all groups.
      All correlations were maintained in healthy controls and in patients with
      relapsing-remitting multiple sclerosis. The highest SNR was present in bookend
      perfusion, while the highest coefficient of variation was present in white matter
      lesions. CONCLUSIONS: Agreement between pseudocontinuous arterial spin-labeling
      and bookend technique CBF measurements is demonstrated in healthy controls and
      patients with relapsing-remitting MS.

PMID- 27686493
TI  - Causes of hepatic capsular retraction: a pictorial essay.
AB  - : Hepatic capsular retraction refers to the loss of the normal convex hepatic
      contour, with the formation of an area of flattening or concavity. This can
      result from myriad causes, including intrinsic hepatic conditions such as
      cirrhosis, biliary obstruction, benign tumours, malignancy and infections, as
      well as extrahepatic causes such as trauma. This article aims to provide
      familiarity with this wide spectrum of conditions, including mimics of hepatic
      capsular retraction, by highlighting the anatomic, pathologic and imaging
      features that help distinguish these entities from one another. TEACHING POINTS:
      * Hepatic capsular retraction can occur due to various intrinsic or extrinsic
      hepatic causes. * Hepatic capsular retraction is observed in both benign and
      malignant conditions. * Recognising associated imaging features can help elicit
      causes of hepatic capsular retraction.

PMID- 27686494
TI  - Chronic administration of [Pyr1] apelin-13 attenuates neuropathic pain after
      compression spinal cord injury in rats.
AB  - Apelin is an endogenous ligand for apelin receptor (APJ) with analgesic effect on
      visceral, analgesic and proanalgesic influences on acute pains in animal models.
      The purpose of this study was to determine the possible analgesic effects of
      [Pyr1] apelin-13 on chronic pain after spinal cord injury (SCI) in rats. Animals
      were randomly divided into three major groups as intact, sham and SCI. The SCI
      group randomly allocated to four subgroups as no treatment, vehicle-treatment
      (normal saline: 10MUl, intrathecally) and two subgroups with intrathecal
      injection (i.t) of 1MUg and 5MUg of [Pyr1] apelin-13. After laminectomy at T6-T8
      level, spinal cord compression injury was induced using an aneurysm clip. Vehicle
      or [Pyr1] apelin-13 injected from day1 post SCI and continued for a week on a
      daily basis. Pain behaviors and locomotor activity were monitored up to 8weeks.
      At the end of the experiments, intracardial paraformaldehyde perfusion was made
      under deep anesthesia in some animals for histological and immunohistochemistry
      evaluations. Western blot technique was also done to detect caspase-3 in fresh
      spinal cord tissues. SCI decreased nociceptive thresholds and locomotor scores.
      Administration of [Pyr1] apelin-13 (1MUg and 5MUg) improved locomotor activity
      and reduced pain symptoms, cavity size and caspase-3 levels. Results showed long
      term beneficial effects of [Pyr1] apelin-13 on neuropathic pain and locomotion.
      Therefore, we may suggest [Pyr1] apelin-13 as a new option for further
      neuropathic pain research and a suitable candidate for ensuing clinical trials in
      spinal cord injury arena.

PMID- 27686492
TI  - Protein glycosylation in cancers and its potential therapeutic applications in
      neuroblastoma.
AB  - Glycosylation is the most complex post-translational modification of proteins.
      Altered glycans on the tumor- and host-cell surface and in the tumor
      microenvironment have been identified to mediate critical events in cancer
      pathogenesis and progression. Tumor-associated glycan changes comprise increased
      branching of N-glycans, higher density of O-glycans, generation of truncated
      versions of normal counterparts, and generation of unusual forms of terminal
      structures arising from sialylation and fucosylation. The functional role of
      tumor-associated glycans (Tn, sTn, T, and sLea/x) is dependent on the interaction
      with lectins. Lectins are expressed on the surface of immune cells and
      endothelial cells or exist as extracellular matrix proteins and soluble adhesion
      molecules. Expression of tumor-associated glycans is involved in the
      dysregulation of glycogenes, which mainly comprise glycosyltransferases and
      glycosidases. Furthermore, genetic and epigenetic mechanisms on many glycogenes
      are associated with malignant transformation. With better understanding of all
      aspects of cancer-cell glycomics, many tumor-associated glycans have been
      utilized for diagnostic, prognostic, and therapeutic purposes. Glycan-based
      therapeutics has been applied to cancers from breast, lung, gastrointestinal
      system, melanomas, and lymphomas but rarely to neuroblastomas (NBs). The success
      of anti-disialoganglioside (GD2, a glycolipid antigen) antibodies sheds light on
      glycan-based therapies for NB and also suggests the possibility of protein
      glycosylation-based therapies for NB. This review summarizes our understanding of
      cancer glycobiology with a focus of how protein glycosylation and associated
      glycosyltransferases affect cellular behaviors and treatment outcome of various
      cancers, especially NB. Finally, we highlight potential applications of
      glycosylation in drug and cancer vaccine development for NB.

PMID- 27686495
TI  - Coexisting giant splenic artery and portal vein aneurysms leading to non
      cirrhotic portal hypertension: a case report.
AB  - BACKGROUND: Splenic artery aneurysms are the commonest visceral and third most
      common abdominal artery aneurysms, having a strong association with both
      pregnancy and multiparity. Here we report possibly the first case of a giant
      splenic artery aneurysm in association with a smaller portal vein aneurysm, in a
      woman who had never conceived, leading to non-cirrhotic portal hypertension. CASE
      PRESENTATION: A 40-year-old Pakistani Asian woman who had no evidence of liver
      cirrhosis presented in April 2016 for a diagnostic workup of ascites, massive
      splenomegaly, and pancytopenia. An abdominal ultrasound followed by computed
      tomography angiography showed a giant aneurysm in her splenic artery and another
      smaller one in her portal vein. She underwent splenectomy and excision of the
      splenic artery aneurysm. Surgical findings included a giant splenic artery
      aneurysm pressing on her portal vein and causing its aneurysmal dilatation. On
      her first review in July 2016, she was generally in good health, ascites had
      subsided, and her full blood count was normal. Her portal vein aneurysmal
      dilatation, which was presumed to be secondary to the pressure effect from the
      splenic artery aneurysm, had shrunken remarkably in size. CONCLUSION: A giant
      splenic artery aneurysm can cause non-cirrhotic portal hypertension and should be
      treated with splenectomy and aneurysmectomy.

PMID- 27686496
TI  - Transient Kinetic Analysis of ATP Hydrolysis by the CCT/TRiC Chaperonin.
AB  - The chaperonin-containing t-complex polypeptide 1 (CCT, also known as TRiC)
      assists protein folding in an ATP-dependent manner. CCT/TRiC was mixed rapidly
      with different concentrations of ATP, and the amount of phosphate formed upon ATP
      hydrolysis was measured as a function of time using the coumarin-labeled
      phosphate-binding protein method. Two burst phases were observed, followed by a
      lag phase and then a linear steady-state phase of ATP hydrolysis. The phases were
      assigned by (i) determining their dependence on ATP and K+ concentrations and
      (ii) by measuring their sensitivity to the mutation Gly345->Asp in subunit CCT4,
      which decreases cooperativity in ATP binding. The values of the observed rate
      constants corresponding to the burst phases are found to decrease with increasing
      ATP and K+ concentrations, thereby indicating that the apo state of CCT/TRiC is
      in equilibrium between several conformations and that "conformational selection"
      by ATP takes place before hydrolysis. The amplitude of the lag phase, which
      follows, decreases with increasing ATP concentrations, thus indicating that it
      reflects a transition between states with low affinity for ATP and a state with
      high affinity for ATP that is predominant under steady-state conditions. A
      kinetic model based on the data is suggested, in which CCT/TRiC is in equilibrium
      between a relatively large number of states that are distinguished kinetically,
      in agreement with its proposed sequential allosteric mechanism.

PMID- 27686497
TI  - The gender gap among school children in poor rural areas of western China:
      evidence from a multi-province dataset.
AB  - BACKGROUND: The gender gap remains a major impediment in the path towards
      equality and it is especially wide in low-income countries. Up to the early
      2000s, many studies documented extensive inequalities in China: girls had poorer
      health, less nutrition and less education than their male counterparts. The goal
      of this study is to examine whether the gender gap persists, given that China is
      now making the transition into the ranks of upper-middle income countries. We
      consider educational outcomes, mental and physical health status, as well as non
      cognitive outcomes. METHODS: We draw on a dataset containing 69,565 observations
      constructed by combining data from 7 different school-level surveys spanning 5
      provinces. The surveys were all conducted by the authors between 2008 and 2013
      using uniform survey instruments and data collection protocols in randomly
      selected schools across western provinces in rural China. The sample children
      range in age from 9 to 14 years (with 79 % of the sample being aged 10 to 12).
      Our analysis compares rural girls with rural boys in terms of 13 different
      indicators. RESULTS: With the exception of anemia rates, the health outcomes of
      girls are equal to those of boys. Girls and boys are statistically identical in
      terms of weight-for-age, height-for-age, and prevalence of intestinal worm
      infections. Girls performed better than boys on five of six cognitive and
      educational performance indicators. Girls performed worse than boys on all mental
      health indicators. All estimates are robust to the inclusion of different age
      ranges, controlling for the level of household assets, ethnic minority status, as
      well as the addition of provincial dummies. CONCLUSIONS: Our findings suggest
      that with the exception of non-cognitive outcomes, anemia and standardized math
      test scores, the gender gap in our study areas in China appears to be
      diminishing.

PMID- 27686498
TI  - Relationship between birth weight and total cholesterol concentration in
      adulthood: A meta-analysis.
AB  - BACKGROUND: Although a substantial number of studies have investigated the
      relationship between birth weight and serum cholesterol later in life, the
      results vary extensively. The aim of this study was to explore the relationship
      between birth weight and total cholesterol concentration in adulthood. METHODS:
      We considered the results of several published observational studies that
      reported the association between birth weight and total cholesterol concentration
      in adulthood. The associations were assessed by linear regression coefficients.
      Summary regression coefficients with 95% confidence intervals (CI) were computed
      using random-effects models. Subgroup and sensitivity analyses were also
      conducted to explore possible explanations for heterogeneity among the studies.
      RESULTS: A total of 20 studies with 26,122 participants were identified. After
      adjustment for adult body mass index, the summary regression coefficient for an
      increment in birth weight of 1 kg was -0.09 mmol/L (95% CI: -0.13, -0.05) for men
      without heterogeneity (I2 = 17.2%) and -0.08 mmol/L (95% CI: -0.13, -0.03) for
      women with low heterogeneity (I2 = 34.0%). Stratified and sensitivity analyses
      generally confirmed the robustness of the findings in men. However, subgroup
      analyses by age indicated that the association of birth weight with total
      cholesterol was statistically significant only in women aged <50 years. There was
      no evidence of publication bias in these studies. CONCLUSION: Based on our
      results, lower birth weight was found to be associated with higher concentrations
      of total cholesterol in men aged >18 years and in women aged <50 years.

PMID- 27686499
TI  - Maternal antineuronal antibodies and risk of childhood autism spectrum disorders:
      A case-control study.
AB  - BACKGROUND: The etiology of autism is complex, and may involve the interaction
      between genetic and environmental factors. Recent studies suggested an
      association between maternal immune response and this disorder. METHODS: Forty
      nine women with autistic children (cases) were studied in comparison with 73
      women with normal children (controls). After interviewing for sociodemographic
      and clinical information, mothers' sera were tested for the presence of
      antineuronal antibodies. RESULTS: Mothers of autistic children had significantly
      higher seropositivity for anti-Yo antibodies (34.7%) than control women (13.7%),
      with an (adjusted odds ratio of 2.60 (95% confidence interval, 1.03-6.61;
      p=0.044). Similarly, women with autistic children showed significantly higher
      seropositivity for antiamphiphysin than the control group (40.8% vs. 17.8%), with
      an adjusted odds ratio of 2.54 (95% confidence interval, 1.07-6.04; p=0.035). No
      significant association was found between autism spectrum disorders and maternal
      anti-Hu antibodies and anti-Ri antibodies, and the history of autoimmune
      diseases. CONCLUSION: Some maternal antineuronal antibodies may contribute
      significantly to the risk of childhood autism.

PMID- 27686500
TI  - Verification of a formula developed to predict the postoperative intraocular
      pressure after cataract surgery in primary angle-closure glaucoma.
AB  - BACKGROUND: The aim of this study was to verify the accuracy of a formula
      predicting postoperative intraocular pressure (IOP) after phacoemulsification and
      intraocular lens implantation (PHCE-IOL) in primary angle-closure glaucoma
      (PACG). In a retrospective chart review of patients with PACG who underwent PHCE
      IOL between 2011 and 2014, we collected preoperative IOP, axial length, anterior
      chamber depth (ACD), number of pre-PHCE glaucoma medications, and IOP and
      glaucoma medications at 1 month and 3 months post-PHCE. METHODS: Post-PHCE IOP
      values at 1 month and 3 months were compared with those predicted using the
      formula: postoperative IOP = 6.354 + 0.186 pre-PHCE IOP * pre-PHCE ACD.
      Agreements between measured and predicted IOP values were analyzed using
      correlation coefficients and Bland-Altman plots. RESULTS: Of the 62 eyes
      included, the average pre-PHCE IOP was 19.47 +/- 5.84 mm Hg. Post-PHCE IOP values
      were 14.94 +/- 4.03 mm Hg at 1 month and 14.21 +/- 3.51 mm Hg at 3 months.
      Patients using more preoperative medications tended to show greater postoperative
      declines in medication usage. Predicted IOP significantly correlated with post
      PHCE IOP measured at 1 month (R = 0.314, p = 0.013) and 3 months (R = 0.325, p =
      0.01). Bland-Altman plots of difference against average of measured and estimated
      IOP revealed two cases falling outside+/-1.96 standard deviation at 1 month, and
      five cases at 3 months, indicating good consistency between measurement and
      prediction. CONCLUSION: This formula was useful for predicting IOP at 1 month and
      3 months after PHCE-IOL in PACG. It aids clinicians in preoperative assessment of
      whether PHCE-IOL alone is likely to achieve acceptable postoperative IOP control.

PMID- 27686501
TI  - Higher platelet counts are associated with metabolic syndrome independent of
      fatty liver diagnosis.
AB  - BACKGROUND: Platelet count (PC) and fatty liver are both associated with
      metabolic syndrome (MS), obesity, and type 2 diabetes. While PC increases in
      obesity and type 2 diabetes, the severity of hepatic fibrosis caused by fatty
      liver reduces PC. We aimed to investigate the correlation of PC and MS in
      patients with and without fatty liver. METHODS: We enrolled consecutive patients
      who received health check-ups at Taipei Veterans General Hospital from 2002 to
      2009. Ultrasonography was used to diagnose fatty liver, and MS was diagnosed
      according to the criteria defined by the International Diabetes Federation Task
      Force on Epidemiology and Prevention. RESULTS: Among the 29,797 patients, MS was
      present in 28.74%. Higher PC was correlated with MS using multivariate analysis,
      while fatty liver had the strongest association with MS. After dividing the
      patients by the presence or absence of fatty liver, higher PC was still
      associated with MS in both groups. The patients were further stratified by age
      and gender, and MS was correlated with PC among all age groups in women and in
      men under 60 years of age; however, the association between PC and MS did not
      reach statistical difference in men older than 60 years. CONCLUSION: There is a
      significant correlation between PC and MS, and the correlation exists independent
      of gender, age, and fatty liver. PC may act as a surrogate marker for MS, and
      physicians should be concerned with the presence of MS among patients with high
      PC.

PMID- 27686502
TI  - Does intrauterine insemination timing matter for achieving pregnancy during
      ovulation induction using gonadotropins? A retrospective cohort study.
AB  - BACKGROUND: Intrauterine insemination (IUI) is a commonly used procedure to
      increase the infertile couples' chance of pregnancy. Single or double
      insemination and different timing choices are modifications of this intervention.
      The aim of this study was to elucidate the effect of the IUI procedure on
      clinical pregnancy rates when performed at 24 hours or 36 hours after ovulation
      triggered by human chorionic gonadotropin (hCG) following ovulation induction
      with gonadotropins. METHODS: One hundred and thirteen women diagnosed with
      polycystic ovarian syndrome (PCOS) (as per Rotterdam's criteria) or unexplained
      infertility, who were treated using gonadotropins for ovulation induction and IUI
      for increasing fertilization potential, were recruited from the medical records
      of the infertility clinic. Demographic features, cycle outcomes, and clinical
      pregnancy rates of the patients were compared based on two different timing
      strategies of IUI (24 hours and 36 hours) following ovulation trigger using hCG.
      RESULTS: Clinical pregnancy rates per cycle were 22.9% in the PCOS group and
      26.9% in the unexplained group. The clinical pregnancy rates according to the
      timing of IUI were found to be similar for PCOS patients, unlike patients with
      unexplained infertility whose clinical pregnancy rates were significantly better
      when the IUI procedure was performed 24 hours following the hCG trigger. The
      cycle day of hCG trigger was also found to be significantly related to clinical
      pregnancy rate as utilizing a later hCG trigger day appeared to positively affect
      the odds of clinical pregnancy establishment. CONCLUSION: IUI performed at either
      24 hours or 36 hours after ovulation triggered by hCG injection does not change
      clinical pregnancy rates for PCOS patients. Patients with unexplained infertility
      seem to benefit from earlier IUI procedures, which increases their fertility
      potential during ovulation induction with gonadotropins. Avoiding earlier than
      physiologically needed artificial-hCG triggering before IUI procedures results
      with better pregnancy rates.

PMID- 27686503
TI  - December 2016, Editor-in-Chief Letter.

PMID- 27686504
TI  - Intraventricular Meningiomas: A Series of 42 Patients at a Single Institution and
      Literature Review.
AB  - BACKGROUND: Primary intraventricular meningiomas (IVMs) make up 0.5%-5% of all
      intracranial meningiomas and represent one of the most challenging lesions in
      neurosurgery. METHODS: Between 1990 and 2013, 42 patients (30 female, 12 male;
      mean age, 43.6 years) underwent resection of their IVM. The removal was performed
      by a posterior parietal approach in 19 of the 40 lateral ventricle tumors, and 1
      third ventricle meningioma. The transcallosal approach was used for 3
      meningiomas, and patients with other lesions underwent temporal (7 cases) and
      temporoparietal approaches (12 patients), respectively. RESULTS: The most common
      presenting signs were increased intracranial pressure (83.3%), visual impairment
      (78.6%) and cognitive changes (50%). Forty lesions (95.2%) arose in the lateral
      ventricles, and 2 (4.8%) in the third ventricle, ranging in size from 3 to 10 cm.
      Total removal was achieved in 39 cases and the pathology report disclosed World
      Health Organization grade I lesions in 41 cases. Hydrocephalus, cerebrospinal
      fluid leakage, and cerebral edema were the postoperative complications (7.15%); 1
      patient died of respiratory problems not directly related to surgery. Thirty-five
      patients (83.3%) showed a 6-month Glasgow Outcome Scale of 5. One patient, who
      underwent partial resection, presented a recurrence after 1 year that remained
      stable until last follow-up. CONCLUSIONS: IVMs usually reach a large size before
      being diagnosed. Surgical treatment is the most suitable option and total removal
      should represent the main goal of the procedure. The posterior parietal
      transulcal approach and the temporoparietal approach are the most common surgical
      routes used in our series.

PMID- 27686505
TI  - Fatal Superior Sagittal Sinus and Torcular Thrombosis After Vestibular Schwannoma
      Surgery: Report of a Rare Complication and Review of the Literature.
AB  - BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare condition with the
      potential to cause severe morbidity and mortality. CVST can also occur after
      vestibular schwannoma (VS) surgery with the thrombosis of transverse and sigmoid
      sinus. However, there is not a single report of superior sagittal sinus (SSS)
      thrombosis after VS surgery reported in the literature. CASE DESCRIPTION: A 45
      year-old woman presented to our center with large left-sided solid cystic VS. On
      admission she was dehydrated, and after clinical stabilization, she underwent
      gross total excision of tumor through left retromastoid suboccipital craniotomy
      after cerebrospinal fluid drainage through an external ventricular drain. Surgery
      was uneventful, but postoperatively she had an episode of seizure. Immediate
      postoperative computed tomography (CT) brain scan was normal with good operative
      cavity. However, 24 hours later, she developed left-sided motor deficit, and a
      repeat CT scan showed right frontal parenchymal hemorrhage with intraventricular
      extension. On further evaluation, magnetic resonance venography showed entire SSS
      thrombosis, with patent bilateral transverse and sigmoid sinuses. She was not
      started on the anticoagulants in view of intracranial hemorrhage. Subsequently,
      she underwent right-sided decompressive craniectomy because there was progressive
      deterioration in her Glasgow Coma Scale, and she succumbed despite all efforts.
      Retrospectively, dehydration and intracranial hypotension could be likened to her
      sinus thrombosis. CONCLUSIONS: This case underscores the significance of adequate
      optimization of the patients prior to surgery, besides adequate operative skills
      to avoid this rare but serious complication of SSS and torcular thrombosis after
      VS surgery.

PMID- 27686506
TI  - Clinical Impact and Implication of Real-Time Oscillation Analysis for Language
      Mapping.
AB  - BACKGROUND: We developed a functional brain analysis system that enabled us to
      perform real-time task-related electrocorticography (ECoG) and evaluated its
      potential in clinical practice. We hypothesized that high gamma activity (HGA)
      mapping would provide better spatial and temporal resolution with high signal-to
      noise ratios. METHODS: Seven awake craniotomy patients were evaluated. ECoG was
      recorded during language tasks using subdural grids, and HGA (60-170 Hz) maps
      were obtained in real time. The patients also underwent electrocortical
      stimulation (ECS) mapping to validate the suspected functional locations on HGA
      mapping. The results were compared and calculated to assess the sensitivity and
      specificity of HGA mapping. For reference, bedside HGA-ECS mapping was performed
      in 5 epilepsy patients. RESULTS: HGA mapping demonstrated functional brain areas
      in real time and was comparable with ECS mapping. Sensitivity and specificity for
      the language area were 90.1% +/- 11.2% and 90.0% +/- 4.2%, respectively. Most HGA
      positive areas were consistent with ECS-positive regions in both groups, and
      there were no statistical between-group differences. CONCLUSIONS: Although this
      study included a small number of subjects, it showed real-time HGA mapping with
      the same setting and tasks under different conditions. This study demonstrates
      the clinical feasibility of real-time HGA mapping. Real-time HGA mapping enabled
      simple and rapid detection of language functional areas in awake craniotomy. The
      mapping results were highly accurate, although the mapping environment was noisy.
      Further studies of HGA mapping may provide the potential to elaborate complex
      brain functions and networks.

PMID- 27686507
TI  - Benign Glandular Schwannoma in Basal Ganglia.
AB  - BACKGROUND: The oncogenesis and biologic behaviors of benign glandular schwannoma
      have not been clinically unveiled because of its rarity and variability. CASE
      DESCRIPTION: However, we report a young male patient who presented with a benign
      glandular schwannoma in the basal ganglia, a site that has not been reported in
      any literature. Histologically, the samples are composed of spindle-shaped cells
      and variable glandular structures. The spindle-shaped cells are identified with
      the appearance of Antoni A and Antoni B zones. Moreover, the glandular structures
      are lined by stratified epithelial cells, glandular epithelium cells, intestinal
      epithelial cells, and few degenerative syncytial macrophage cells. Hemorrhage,
      necrosis and cystic changes were observed in the specimen cells, but no mitotic
      figures were found. The immunohistochemical results showed that the spindle cells
      were stained with S-100 protein, but lacked carcinoembryonic antigen (CEA),
      cytokeratin pan (AE1/AE3) (CK), synaptophysin, chromogranin A, and glial
      fibrillary acidic protein reactivity after surgery. Meanwhile, the glandular
      epithelium cells mostly consisted of glandular epithelium and stratified
      epithelium cells stained with CEA, chromogranin A, and CK antigen. CONCLUSIONS:
      Therefore, the morphologic and immunohistochemical findings support the diagnosis
      of benign glandular schwannoma.

PMID- 27686508
TI  - Risk of Infection After Local Field Potential Recording from Externalized Deep
      Brain Stimulation Leads in Parkinson's Disease.
AB  - OBJECTIVE: Adaptive deep brain stimulation (aDBS) controlled by local field
      potentials (LFPs) is considered a promising treatment for advanced Parkinson's
      disease (PD). The clinical research investigating aDBS functioning is performed
      using external deep brain stimulation (DBS) systems that require LFP recording
      through the temporary externalization of DBS leads. Although research examining
      LFP was first undertaken more than 20 years ago, only a few studies concern lead
      externalization and LFP recording safety. In the present retrospective study, we
      assessed the risk of infection related to these procedures. METHODS: A total of
      105 patients with PD who underwent DBS surgery and lead externalization at our
      hospital from 2002 to 2014 were included in the present study. The medical
      records were used to collect clinical data and information concerning surgical
      site infections. We assessed the infection incidence in our cohort and the risk
      of infection related to the LFP recording procedure. RESULTS: The incidence of
      infections in patients who underwent lead externalization was 2.8%, which was
      consistent with the postoperative infectious risk reported in the literature
      (Wilcoxon signed rank test; P > 0.05). Moreover, the LFP recording procedure did
      not significantly increase the infection risk (LFP recordings vs. no LFP
      recordings: 2.5% vs. 4.2%; Fisher exact test; P > 0.05). CONCLUSIONS: DBS lead
      externalization and LFP recording are safe and do not increase the postoperative
      infection risk in patients with PD who undergo DBS surgery. Our retrospective
      study supported further clinical research in the field of LFP-based aDBS.

PMID- 27686510
TI  - The safety and efficacy of ramucirumab in combination with docetaxel in the
      treatment of lung cancer.
AB  - INTRODUCTION: Angiogenesis is critical for tumor growth, proliferation and
      metastasis with the crucial role of Vascular Endothelial Growth factor (VEGF)
      pathway. Ramucirumab is a monoclonal antibody that specifically targets the
      extracellular domain of Vascular Endothelial Growth Factor Receptor 2. Areas
      covered: We performed a search on Medline to browse the current literature on
      Ramucirumab and anti-angiogenic agents, for the treatment of NSCLC. The REVEL
      study demonstrated a significant improvement of response rate, progression-free
      survival and overall survival by adding ramucirumab to docetaxel compared to
      docetaxel plus a placebo in second-line treatment of advanced non-small cell lung
      cancer, irrespective of histology, with an acceptable safety profile. This
      article has for objective to summarize efficacy and safety data of the use of
      ramucirumab in combination with docetaxel in second line in NSCLC. Expert
      commentary: REVEL constitutes the first significant advance in second-line
      setting for patients eligible to anti-angiogenic therapy. The landscape of post
      platinum therapy in NSCLC is considerably evolving and the role of ramucirumab or
      other anti-angiogenic agents as nintedanib in this setting has to be discussed
      for each patient with other available treatment options, among which immune
      checkpoints inhibitors, as well as the best treatment sequence.

PMID- 27686509
TI  - Influence of Body Mass Index on Subjective and Objective Measures of Pain,
      Functional Impairment, and Health-Related Quality of Life in Lumbar Degenerative
      Disc Disease.
AB  - OBJECTIVE: To analyze the influence of body mass index (BMI) on subjective and
      objective measures of pain, functional impairment, and health-related quality of
      life in patients with lumbar degenerative disc disease undergoing surgery.
      METHODS: Prospective institutional review board-approved 2-center study,
      measuring visual analog scale (VAS) back and leg pain, Roland-Morris Disability
      Index (RMDI), Oswestry Disability Index (ODI), EuroQol 5D questionnaire, and
      Short Form-12 at baseline, 6 weeks, 6 months, and 1 year postoperatively. T
      scores of objective functional impairment (OFI) were determined using the Timed
      Up and Go (TUG) test. RESULTS: A total of 375 patients with a median BMI of 26.6
      kg/m2 (94 obese patients [BMI >=30 kg/m2]) were included. Obese patients
      presented more VAS back pain (mean, 4.7 vs. 3.6; P = 0.001) and greater
      disability on the RMDI (mean, 12.6 vs. 11.3; P = 0.045). The prevalence and
      severity of OFI were similar in obese and nonobese patients. There was a weak
      positive correlation between BMI and VAS back pain (r = 0.1552; P = 0.0026), on
      both RMDI (r = 0.1138; P = 0.0276) and ODI (r = 0.1075; P = 0.0374). There was no
      correlation between BMI and TUG T-scores (r = 0.0475; P = 0.3585). Obese patients
      were as likely as nonobese patients to show a positive 6-week treatment response,
      and the outcome up to 1 year was similar. CONCLUSIONS: BMI positively correlates
      with VAS back pain, RMDI, and ODI. Standardized TUG T scores reflect the
      patient's degree of OFI well, irrespective of BMI. The TUG test appears to be a
      good means to estimate functional impairment in populations with a high
      prevalence of obesity.

PMID- 27686511
TI  - Insufficient developmental excitatory neuronal activity fails to foster
      establishment of normal levels of inhibitory neuronal activity.
AB  - The nervous system is composed of excitatory and inhibitory neurons. One major
      class of inhibitory neurons release the neurotransmitter gamma-Aminobutyric acid
      (GABA). GABAergic inhibitory activity maintains the balance that is disrupted in
      conditions such as epilepsy. At least some GABAergic neurons are initially
      excitatory and undergo a developmental conversion to convert to inhibitory
      neurons. The mechanism(s) behind this conversion are thought to include a
      critical developmental increase in excitatory activity. To test this hypothesis,
      we subjected ex vivo developing neuronal networks on multi-electrode arrays to
      various stimulation and pharmacological regimens. Synaptic activity of networks
      initially consists of epileptiform-like high-amplitude individual "spikes", which
      convert to organized bursts of activity over the course of approximately 1 month.
      Stimulation of networks with a digitized synaptic signal for 5days hastened the
      decrease of epileptiform activity. By contrast, stimulation for a single day
      delayed the appearance of bursts and instead increased epileptiform signaling.
      GABA treatment reduced total signals in unstimulated networks and networks
      stimulated for 5days, but instead increased signaling in networks stimulated for
      1day. This increase was prevented by co-treatment with (2R)-amino-5
      phosphonopentanoate and 6-cyano-7-nitroquinoxaline-2,3-dione, confirming that
      GABA invoked excitatory activity in networks stimulated for 1day. Glutamate
      increased signals in networks subjected to all stimulation regimens; the GABA
      receptor antagonist bicuculline prevented this increase only in networks
      stimulated for 1day. These latter findings are consistent with the induction of
      so-called "mixed" synapses (which release a combination of excitatory and
      inhibitory neurotransmitters) in networks stimulated for 1day, and support the
      hypothesis that a critical level of excitatory activity fosters the developmental
      transition of GABAergic neurons from excitatory to inhibitory.

PMID- 27686512
TI  - Assessment of Perioperative Ultrasound Workflow Understanding: A Consensus.
AB  - OBJECTIVES: Understanding of the workflow of perioperative ultrasound (US)
      examination is an integral component of proficiency. Workflow consists of the
      practical steps prior to executing an US examination (eg, equipment operation).
      Whereas other proficiency components (ie, cognitive knowledge and manual
      dexterity) can be tested, workflow understanding is difficult to define and
      assess due to its contextual and institution-specific nature. The objective was
      to define the workflow components of specific perioperative US applications using
      an iterative process to reach a consensus opinion. DESIGN: Expert consensus,
      survey study. SETTING: Tertiary university hospital. PARTICIPANTS: This study
      sought expert consensus among a focus group of 9 members of an anesthesia
      department with experience in perioperative US. Afterward, 257 anesthesia faculty
      members from 133 academic centers across the United States were surveyed.
      INTERVENTIONS: A preliminary list of tasks was designed to establish the
      expectations of workflow understanding by an anesthesiology resident prior to
      clinical exposure to perioperative US. This list was modified by a focus group
      through an iterative process. Afterwards, a survey was sent to faculty members
      nationwide, and Likert scale ratings for each task were obtained and reviewed
      during a second round. MEASUREMENTS AND MAIN RESULTS: Consensus among members of
      the focus group was reached after 2 iterations. 72 participants responded to the
      nationwide survey (28%), and consensus was reached after the second round
      (Cronbach's alpha = 0.99, ICC = 0.99) on a final list of 46 workflow-related
      tasks. CONCLUSIONS: Specific components of perioperative US workflow were
      identified. Evaluation of workflow understanding may be combined with cognitive
      knowledge and manual dexterity testing for assessing proficiency in perioperative
      US.

PMID- 27686513
TI  - Mobile Extracorporeal Membrane Oxygenation Teams: The North American Versus the
      European Experience.
AB  - OBJECTIVE: To evaluate differences in the inclusion of anesthesiologists in
      mobile extracorporeal membrane oxygenation (ECMO) teams between North American
      and European centers. DESIGN: A retrospective review of North American versus
      European mobile ECMO teams. The search terms used to identify relevant articles
      were the following: "extracorporeal membrane transport," "mobile ECMO," and
      "interhospital transport." SETTING: MEDLINE review of articles. PARTICIPANTS:
      None. INTERVENTIONS: None. RESULTS: Between 1986 and 2015, 25 articles were
      published that reported the personnel makeup of mobile ECMO teams in North
      America and Europe: 6 from North American centers and 19 from European centers.
      The included articles reported a total of 1,329 cases: 389 (29%) adult-only
      cohorts and 940 (71%) mixed-age cohorts. Among North American studies, 0 of 6
      (0%) reported the presence of an anesthesiologist on the mobile ECMO team in
      contrast to European studies, in which 10 of 19 (53%) reported the inclusion of
      an anesthesiologist (Fisher exact p for difference = 0.05). In terms of number of
      cases, this discrepancy translated to 543 total cases in North America (all
      without an anesthesiologist) and 499 cases in Europe (37%) including an
      anesthesiologist on the team (Fisher exact p for difference<0.001). CONCLUSIONS:
      This study demonstrated significant geographic discrepancies in the inclusion of
      anesthesiologists on mobile ECMO teams, with European centers more likely to
      incorporate an anesthesiologist into the mobile ECMO process compared with North
      American centers.

PMID- 27686514
TI  - Preparation of protein nano-objects by assembly of polymer-grafted proteins.
AB  - We carried out surface-grafting from proteins and their assembling into objects
      with unique nanostructured materials (nano-objects). To immobilize polymer
      initiating sites, amino groups of bovine serum albumin (BSA) were allowed to
      react with iniferter groups (BSA-i). Then, graft polymerization of N-isopropyl
      acrylamide (NIPAM) was performed by light-initiated living radical polymerization
      from immobilized iniferter moieties of BSA-i. The polymer-grafted BSA (BSA-g
      PNIPAM) was assembled into nano-objects through the precipitation of PNIPAM graft
      chains and their sizes and morphologies were tuned by the chain length, the
      density and the chemical structure of graft polymers in addition to the
      environmental conditions such as temperature and pH. It was possible to retain
      the structures of nano-objects by thermal denaturation via heat treatment.
      Fluorescent substances were encapsulated in particulate nano-objects
      (nanoparticles) assembled from PNIPAM-g-BSA and their release could be regulated
      by tuning pH and temperature. Next, further graft polymerization from PNIPAM
      grafted BSA was carried out by living radical polymerization of a cationic
      monomer, N,N-dimethylamino propyl acrylamide methyl chloride quaternary
      (DMAPAAQ). The grafted polymer was composed of a block copolymer of PNIPAM and a
      cationic polymer (PDMAPAAQ) and the gel-like nano-object was generated by
      increasing temperature. In contrast to PNIPAM-g-BSA, it became insoluble even
      when the temperature decreased, probably due to the electrostatic association
      between anionic regions of BSA and cationic regions of graft polymers. Coating of
      BSA-g-P(NIPAM-b-DMAPAAQ) enabled to form a uniform thin layer over a human hair.
      A free-standing membrane could be obtained by peeling from a water repellent
      substrate to create a porous membrane.

PMID- 27686515
TI  - Compression tests of Fusarium graminearum ascocarps provide insights into the
      strength of the perithecial wall and the quantity of ascospores.
AB  - The plant pathogenic ascomycete Fusarium graminearum produces perithecia on corn
      and small grain residues. These perithecia forcibly discharge ascospores into the
      atmosphere. Little is known about the relationship among the strength of the
      perithecial wall, the age of the perithecium, and the quantity of ascospores
      produced. We used a mechanical compression testing instrument to examine the
      structural failure rate of perithecial walls from three different strains of F.
      graminearum (two wild type strains, and a mutant strain unable to produce asci).
      The force required to compress a perithecium by one micrometer (the mean
      perithecium compression constant, MPCC) was used to determine the strength of the
      perithecial wall. Over the course of perithecial maturation (5-12days after the
      initiation of perithecial development), the MPCC was compared to the number of
      ascospores contained inside the perithecia. The MPCC increased as perithecia
      matured, from 0.06NMUm-1 at 5d to 0.12NMUm-1 at 12d. The highest number of
      ascospores was found in older perithecia (12d). The results indicated that for
      every additional day of perithecial aging, the perithecia become more resilient
      to compression forces. Every additional day of perithecial aging resulted in ~900
      more ascospores. Knowledge of how perithecia respond to external forces may
      provide insight into the development of ascospores and the accumulation of turgor
      pressure. In the future, compression testing may provide a unique method of
      determining perithecial age in the field, which could extend to management
      practices that are informed by knowledge of ascospore release and dispersal.

PMID- 27686516
TI  - The association between location, age and advanced colorectal adenoma
      characteristics: a propensity-matched analysis.
AB  - PURPOSE: Evidence supports an association between certain colorectal adenoma
      characteristics and predisposition to cancer. The association between anatomical
      location of colorectal adenoma, age and advanced adenomas needs attention. The
      objective of this study was to evaluate the possible association between
      occurrence of sporadic advanced adenomas with location and age. MATERIALS AND
      METHODS: A cross-sectional study using baseline data from index colonoscopy from
      a randomized controlled trial evaluating chemopreventive treatment against
      recurrence of colorectal adenomas was performed. Inclusion criteria for patients
      were one adenoma of >1 cm in diameter or multiple adenomas of any size, or an
      adenoma of any size and familial disposition for colorectal cancer. Multivariate
      regression and propensity score-matched analyses were used to correlate location
      of adenomas and age with advanced adenoma features. RESULTS: In this study, 2149
      adenomas were removed in 1215 patients. Advanced colorectal adenomas primarily
      occurred in the anal part of the colon. Older age was associated with more
      adenomas and more oral occurrence of adenomas, as well as a higher risk of
      advanced adenomas. Surprisingly, specifically for the oral adenomas the risk of
      advanced adenoma seems to be lower for older patients compared with younger.
      CONCLUSIONS: This study presents new results with regard to association between
      age, location of adenomas and risk of advanced adenomas. The results indicate
      that sigmoidoscopy for screening purposes may be obsolete, and add to the
      existing literature on which future guidelines for screening may be based.

PMID- 27686517
TI  - A case of recent myocardial infarction with cardiac failure.
AB  - CLINICAL INTRODUCTION: A 50-year-old hypertensive smoker presented with a typical
      angina of 2 days duration. An urgent ECG revealed extensive anterior wall
      myocardial infarction. In view of the delayed presentation, the patient was
      conservatively managed with heparin. In-hospital echocardiogram showed akinesia
      of entire left anterior descending artery (LAD) territory with severe left
      ventricular (LV) dysfunction. He was discharged with a plan for early coronary
      intervention. However, he presented a fortnight later with acute pulmonary
      oedema. General appraisal revealed a restless individual who was dyspnoeic and
      diaphoretic at rest. On clinical examination, the patient was in hypotension with
      features of biventricular failure. A 12-lead ECG showed QS pattern with
      persistent ST segment elevation in precordial leads. The chest radiograph
      demonstrated features of pulmonary oedema, cardiomegaly and bilateral pleural
      effusion. Creatine Phosphokinase-MB (CPK-MB) was negative. A preliminary
      transthoracic echocardiography was done (figure 1 and see online supplementary
      video 1). QUESTION: What is the most likely diagnosis based on the
      echocardiogram? LV pseudo-aneurysm with contained ruptureDissecting intramural
      haematoma of LV apexVentricular apical aneurysm with thrombusLV non-compaction
      with prominent ventricular trabaculations.

PMID- 27686518
TI  - The long and unfinished journey of hyperglycaemia and heart failure research.

PMID- 27686519
TI  - Influenza vaccine as a coronary intervention for prevention of myocardial
      infarction.
AB  - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality
      globally. Influenza is one of the leading infectious causes of morbidity and
      mortality globally, and evidence is accumulating that it can precipitate acute
      myocardial infarction (AMI). This is thought to be due to a range of factors
      including inflammatory release of cytokines, disruption of atherosclerotic
      plaques and thrombogenesis, which may acutely occlude a coronary artery. There is
      a large body of observational and clinical trial evidence that shows that
      influenza vaccine protects against AMI. Estimates of the efficacy of influenza
      vaccine in preventing AMI range from 15% to 45%. This is a similar range of
      efficacy compared with the accepted routine coronary prevention measures such as
      smoking cessation (32-43%), statins (19-30%) and antihypertensive therapy (17
      25%). Influenza vaccine should be considered as an integral part of CVD
      management and prevention. While it is recommended in many guidelines for
      patients with CVD, rates of vaccination in risk groups aged <65 years are very
      low, in the range of 30%. The incorporation of vaccination into routine CVD
      prevention in patient care requires a clinical practice paradigm change.

PMID- 27686520
TI  - Optimisation of nutritional requirements for dopamine synthesis by calcium
      alginate-entrapped mutant strain of Aspergillus oryzae EMS-6.
AB  - The optimisation of nutritional requirements for dopamine (DA) synthesis by
      calcium alginate-entrapped mutant variant of Aspergillus oryzae EMS-6 using
      submerged fermentation technique was investigated. A total of 13 strains were
      isolated from soil. Isolate I-2 was selected as a better producer of DA and
      improved by exposing with ethyl methylsulphonate (EMS). EMS-6 was selected as it
      exhibited 43 MUg/mL DA activity. The mutant variable was further treated with low
      levels of l-cysteine HCl to make it resistant against diversion and environmental
      stress. The conidiospores of mutant variant were entrapped in calcium alginate
      beads for stable product formation. EMS-6 gave maximum DA activity (124 MUg/mL)
      when supplemented with 0.1% peptone and 0.2% sucrose, under optimised parameters
      viz. pH 3, temperature of 55  degrees C and incubation time of 70 min. The study
      involves the high profile of DA activity and is needed, as DA is capable to
      control numerous neurogenic disorders.

PMID- 27686521
TI  - NOTCH1 mutation in type II Hodgkin transformation of chronic lymphocytic
      leukemia.

PMID- 27686522
TI  - Association of rotavirus strains and severity of gastroenteritis in Indian
      children.
AB  - Rotavirus is the leading cause of severe and dehydrating diarrhea in children
      aged under 5 years. We undertook this hospital-based surveillance study to
      examine the possible relationship between the severity of diarrhea and the
      various G-group rotaviruses circulating in India. Stool samples (n = 2,051) were
      systematically collected from 4,711 children aged <5 years admitted with severe
      acute gastroenteritis to 12 medical school centers from April 2011 to July 2012.
      Rotavirus testing was undertaken using a commercially available enzyme
      immunoassay kit for the rotavirus VP6 antigen (Premier Rotaclone Qualitative
      ELISA). Rotavirus positive samples were genotyped for VP7 and VP4 antigens by
      reverse-transcription polymerase chain reaction at a central laboratory. Of the
      stool samples tested for rotavirus antigen, 541 (26.4%) were positive for VP6
      antigen. Single serotype infections from 377 stool samples were compared in terms
      of gastroenteritis severity. Among those with G1 rotavirus infection, very severe
      diarrhea (Vesikari score >= 16) was reported in 59 (33.9%) children, severe
      diarrhea (Vesikari score 11-15) in 104 (59.8%), moderate (Vesikari score 6-10)
      and mild diarrhea (Vesikari score 0-5) in 11 (6.3%). Among those with G2
      infection, very severe diarrhea was reported in 26 (27.4%) children, severe
      diarrhea in 46 (48.4%), and moderate and mild diarrhea in 23 (24.2 %). Among
      those with G9 infection, very severe diarrhea was reported in 47 (54.5%)
      children, severe diarrhea in 29 (33.6%), and moderate and mild diarrhea in 10
      (11.9%). Among those with G12 infection, very severe diarrhea was reported in 9
      (40.9%) children and severe diarrhea in 13 (59.1%). The results of this study
      indicate some association between rotavirus serotypes and severity of
      gastroenteritis.

PMID- 27686523
TI  - The second gamma-H2AX assay inter-comparison exercise carried out in the
      framework of the European biodosimetry network (RENEB).
AB  - PURPOSE: Within the EU RENEB project, seven laboratories have taken part in
      training and harmonisation activities to strengthen triage gamma-H2AX-based
      radiation exposure assessment. This has culminated in a second triage
      biodosimetry exercise. MATERIALS AND METHODS: Whole blood and separated
      lymphocyte samples were homogenously irradiated with 60Co gamma rays at 0.5, 2.5
      (blind samples), 0 and 2 Gy (reference samples). Following post-exposure
      incubations of 4 and 24 h, 16 samples were shipped on ice packs to each partner.
      The samples were stained and scored for gamma-H2AX foci, using manual and/or
      automated fluorescence microscope scoring strategies. Dose estimates were
      obtained and used to assign triage categories to the samples. RESULTS: Average
      dose estimates across all the laboratories correlated well with true doses. The
      most accurate assignment of triage category was achieved by manual scoring of the
      4-h blood and lymphocyte samples. Only three samples out of a total of 46 were
      miscategorized in a way that could have adversely effected the clinical
      management of a radiation casualty. CONCLUSIONS: This inter-comparison exercise
      has demonstrated that following a recent acute radiation exposure, the gamma-H2AX
      assay could be a useful triage tool that can be successfully applied across a
      network of laboratories.

PMID- 27686524
TI  - Renal cell carcinoma survival and body mass index: a dose-response meta-analysis
      reveals another potential paradox within a paradox.
AB  - BACKGROUND: In healthy subjects increasing body mass index (BMI) leads to greater
      mortality from a range of causes. Following onset of specific diseases, however,
      the reverse is often found: called the 'obesity paradox'. But we recently
      observed the phenomenon called the 'paradox within the paradox' for stroke
      patients. OBJECTIVE: The objective of our study was to examine the effect of each
      unit increase in BMI on renal cancer-specific survival (CSS), cancer-specific
      mortality, overall survival (OS) and overall mortality. DESIGN: Random-effects
      generalized least squares models for trend estimation were used to analyze the
      data. Eight studies, comprising of 8699 survivals of 10 512 renal cell carcinoma
      (RCC) patients met the inclusion criteria, including 5 on CSS and 3 on OS.
      RESULTS: The association of BMI with CSS and OS was non-linear (P<0.0001,
      P=0.004, respectively). We observed that CSS increased in relation to BMI,
      indicating that there was the obesity paradox in RCC. However, each unit increase
      in BMI over 25 was associated with decreased OS, indicating that RCC may also
      exhibit a paradox within the paradox. CONCLUSIONS: Inconsistent effects of
      increases in BMI on CSS and OS, as previously observed for stroke, creates a
      paradox (different directions of mortality for different causes) within the
      obesity paradox.

PMID- 27686525
TI  - An unconventional pathway for mitochondrial protein degradation.
AB  - Many vital metabolic pathways take place in mitochondria, but some of the
      associated processes generate toxic substances including reactive oxygen species
      that can damage proteins and DNA. Therefore, it is critical to maintain normally
      functioning mitochondria to achieve proper cellular homeostasis. Along these
      lines, mitochondrial dysfunction is associated with numerous diseases, and
      mitochondria quality control is essential for cell survival. The maintenance of
      functioning mitochondria is particularly important in aging cells, and there is a
      strong relationship between cellular aging and dysfunctional mitochondria. The
      best characterized pathway that is responsible for the elimination of damaged
      mitochondria is mitophagy, a selective type of autophagy. In yeast, mitophagy
      requires the mitochondrial protein Atg32 to serve as a receptor for recognition
      and sequestration by a phagophore. Although conventional mitophagy has been
      extensively studied, recent research suggests that an unconventional pathway,
      which is independent of Atg32, contributes to the removal of mitochondria.

PMID- 27686528
TI  - MicroRNA let-7f-5p Inhibits Porcine Reproductive and Respiratory Syndrome Virus
      by Targeting MYH9.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most
      important viral pathogens in the swine industry. Current antiviral strategies do
      not effectively prevent and control PRRSV. Recent reports show that microRNAs
      (miRNAs) play vital roles in viral infections by post transcriptionally
      regulating the expression of viral or host genes. Our previous research showed
      that non-muscle myosin heavy chain 9 (MYH9) is an essential factor for PRRSV
      infection. Using bioinformatic prediction and experimental verification, we
      demonstrate that MYH9 expression is regulated by the miRNA let-7f-5p, which binds
      to the MYH9 mRNA 3'UTR and may play an important role during PRRSV infection. To
      understand how let-7f-5p regulates PRRSV infection, we analyzed the expression
      pattern of both let-7f-5p and MYH9 in porcine alveolar macrophages (PAMs) after
      infection with either highly pathogenic PRRSV (HP-PRRSV) or classical type PRRSV
      (N-PRRSV) using a deep sequencing approach with quantitative real-time PCR
      validation. Our results showed that both HP-PRRSV and N-PRRSV infection reduced
      let-7f-5p expression while also inducing MYH9 expression. Furthermore, let-7f-5p
      significantly inhibited PRRSV replication through suppression of MYH9 expression.
      These findings not only provide new insights into the pathogenesis of PRRSV, but
      also suggest potential new antiviral strategies against PRRSV infection.

PMID- 27686527
TI  - Identification of DNA methylation changes associated with disease progression in
      subchondral bone with site-matched cartilage in knee osteoarthritis.
AB  - Subchondral bone plays a key role in the development of osteoarthritis, however,
      epigenetics of subchondral bone has not been extensively studied. In this study,
      we examined the genome-wide DNA methylation profiles of subchondral bone from
      three regions on tibial plateau representing disease progression using
      HumanMethylation450 BeadChip to identify progression associated DNA methylation
      alterations. Significant differential methylated probes (DMPs) and differential
      methylated genes (DMGs) were identified in the intermediate and late stages and
      during the transition from intermediate to late stage of OA in the subchondral
      bone. Over half of the DMPs were hyper-methylated. Genes associated with OA and
      bone remodeling were identified. DMGs were enriched in morphogenesis and
      development of skeletal system, and HOX transcription factors. Comparison of DMGs
      identified in subchondral bone and site-matched cartilage indicated that DNA
      methylation changes occurred earlier in subchondral bone and identified different
      methylation patterns at the late stage of OA. However, shared DMPs, DMGs and
      common pathways that implicated the tissue reparation were also identified.
      Methylation is one key mechanism to regulate the crosstalk between cartilage and
      subchondral bone.

PMID- 27686526
TI  - Proteome-wide identification of the endogenous ADP-ribosylome of mammalian cells
      and tissue.
AB  - Although protein ADP-ribosylation is involved in diverse biological processes, it
      has remained a challenge to identify ADP-ribose acceptor sites. Here, we present
      an experimental workflow for sensitive and unbiased analysis of endogenous ADP
      ribosylation sites, capable of detecting more than 900 modification sites in
      mammalian cells and mouse liver. In cells, we demonstrate that Lys residues,
      besides Glu, Asp and Arg residues, are the dominant in vivo targets of ADP
      ribosylation during oxidative stress. In normal liver tissue, we find Arg
      residues to be the predominant modification site. The cellular distribution and
      biological processes that involve ADP-ribosylated proteins are different in
      cultured cells and liver tissue, in the latter of which the majority of sites
      were found to be in cytosolic and mitochondrial protein networks primarily
      associated with metabolism. Collectively, we describe a robust methodology for
      the assessment of the role of ADP-ribosylation and ADP-ribosyltransferases in
      physiological and pathological states.

PMID- 27686529
TI  - Clinical trials of lasers for toenail onychomycosis: The implications of new
      regulatory guidance.
AB  - BACKGROUND: Despite the fact that lasers are presently indicated for the cosmetic
      outcome "temporary increase in clear nail", these devices are increasingly used
      to treat onychomycosis and particularly in patients who are unwilling or unable
      to take oral antifungal medication. The US Food and Drug Administration (FDA)
      recently issued draft guidance for medical device trials for onychomycosis.
      OBJECTIVE: This review evaluates the quality of laser trials for onychomycosis
      and compares the design guidelines for medical devices and antifungal drugs.
      METHOD: The PubMed database up to 29 May 2015 was searched for clinical studies
      of laser treatment for onychomycosis. RESULTS: The evidence demonstrating that
      lasers eradicate pathogenic fungi is limited and published laser trials suffer
      from limitations such as incomplete reporting of randomization and lack of
      stratified analyzes for fingernail/toenail data and infecting organisms.
      Differences in inclusion criteria and efficacy outcomes between drug and device
      guidelines may prevent the comparison of results from device and drug trials.
      CONCLUSION: We propose the standardization of device guidelines to match those of
      antifungal drug trials. Patients and physicians need to be aware of the
      capabilities and limitations of laser treatment for onychomycosis.

PMID- 27686531
TI  - An engineering approach to design of dextran microgels size fabricated by
      water/oil emulsification.
AB  - A correlation, based on fluid mechanics, has been investigated for the mean
      particle diameter of crosslinked dextran microgels (CDMs) prepared via a
      water/oil emulsification methodology conducted in a single-stirred vessel. To
      this end, non-dimensional correlations were developed to predict the mean
      particle size of CDMs as a function of Weber number, Reynolds number and
      viscosity number similar to ones introduced for liquid-liquid dispersions.
      Moreover, a Rosin-Rammler distribution function has been successfully applied to
      the microgel particle size distributions. The correlations were validated using
      experimentally obtained mean particle sizes for CDMs prepared at different
      stirring conditions. The validated correlation is especially applicable to
      medical and pharmaceutical applications where strict control on the mean particle
      size and size distribution of CDMs are extremely essential. [Formula: see text].

PMID- 27686530
TI  - Extraintestinal pathogenic Escherichia coli are associated with intestinal
      inflammation in patients with ulcerative colitis.
AB  - E. coli of the phylogenetic group B2 harbouring Extra intestinal Pathogenic
      Escherichia coli (ExPEC) genes are frequently seen as colonizers of the intestine
      in patients with active ulcerative colitis (UC). In this study, we describe the
      influence of E. coli Nissle (EcN) B2 as add-on treatment to conventional
      therapies in patients with active UC. For this study one hundred active UC
      patients were randomized to ciprofloxacin or placebo for 1 week followed by EcN
      or placebo for 7 weeks. Stool samples were collected at weeks 0, 1, 8, 12, where
      E. coli were characterized and fecal calprotectin was measured. We showed that in
      the active UC patient group receiving Placebo/EcN, fewer patients reached
      remission, in comparison to the patient group receiving Placebo/placebo (p <
      0.05). Active UC patients initially colonized with E. coli B2 had increased fecal
      calprotectin values and Colitis Activity Index scores in comparison to patients
      colonized with E. coli A and D (p < 0.05*). In conclusion, treatment of UC
      patients with E. coli Nissle (B2) does not promote clinical remission and active
      UC patients colonized with E. coli B2 have an increased intestinal inflammation.

PMID- 27686532
TI  - Gamma-H2AX upregulation caused by Wip1 deficiency increases depression-related
      cellular senescence in hippocampus.
AB  - The PP2C family member Wild-type p53-induced phosphatase 1 (Wip1) critically
      regulates DNA damage response (DDR) under stressful situations. In the present
      study, we investigated whether Wip1 expression was involved in the regulation of
      DDR-induced and depression-related cellular senescence in mouse hippocampus. We
      found that Wip1 gene knockout (KO) mice showed aberrant elevation of hippocampal
      cellular senescence and of gamma-H2AX activity, which is known as a biomarker of
      DDR and cellular senescence, indicating that the lack of Wip1-mediated gamma-H2AX
      dephosphorylation facilitates cellular senescence in hippocampus. Administration
      of the antidepressant fluoxetine had no significant effects on the increased
      depression-like behaviors, enriched cellular senescence, and aberrantly
      upregulated hippocampal gamma-H2AX activity in Wip1 KO mice. After wildtype
      C57BL/6 mice were exposed to the procedure of chronic unpredictable mild stress
      (CUMS), cellular senescence and gamma-H2AX activity in hippocampus were also
      elevated, accompanied by the suppression of Wip1 expression in hippocampus when
      compared to the control group without CUMS experience. These CUMS-induced
      symptoms were effectively prevented following fluoxetine administration in
      wildtype C57BL/6 mice, with the normalization of depression-like behaviors. Our
      data demonstrate that Wip1-mediated gamma-H2AX dephosphorylation may play an
      important role in the occurrence of depression-related cellular senescence.

PMID- 27686533
TI  - Ecosystem services sustainability in the Mediterranean Sea: assessment of status
      and trends using multiple modelling approaches.
AB  - Mediterranean ecosystems support important processes and functions that bring
      direct benefits to human society. Yet, marine ecosystem services are usually
      overlooked due to the challenges in identifying and quantifying them. This paper
      proposes the application of several biophysical and ecosystem modelling
      approaches to assess spatially and temporally the sustainable use and supply of
      selected marine ecosystem services. Such services include food provision, water
      purification, coastal protection, lifecycle maintenance and recreation, focusing
      on the Mediterranean region. Overall, our study found a higher number of
      decreasing than increasing trends in the natural capacity of the ecosystems to
      provide marine and coastal services, while in contrast the opposite was observed
      to be true for the realised flow of services to humans. Such a study paves the
      way towards an effective support for Blue Growth and the European maritime
      policies, although little attention is paid to the quantification of marine
      ecosystem services in this context. We identify a key challenge of integrating
      biophysical and socio-economic models as a necessary step to further this
      research.

PMID- 27686534
TI  - Sit-To-Stand Lift: Effects of Lifted Height on Weight Borne and Upper Extremity
      Strength Requirements.
AB  - To prevent back and shoulder injuries to nursing personnel, sit-to-stand lifts
      are used to transfer partial-weight-bearing patients with upper extremity
      strength. However, the weight-bearing capacity and upper extremity strength
      required of patients have not been defined. The objectives of this study were to
      determine: (a) the percentage of body weight borne by the patient when lifted to
      different heights in the lift and (b) whether a patient needs upper extremity
      strength. Nineteen healthy normal-weight volunteers (ages 19-39) were transferred
      from a hospital bed to a wheelchair using (a) a gait belt and (b) a sit-to-stand
      lift. With legs secured in the lift, participants were lifted to five different
      heights (knee angles 120-180 degrees) while holding and not holding the lift
      handles. Participants supported a greater percentage of body weight as they were
      lifted higher, increasing from 60% to almost 100% (p < .01). Holding the handles
      did not have an effect on weight borne overall. At low heights, slightly less
      weight was borne when not using the handles than with them, and no difference in
      weight borne was found at heights near standing (p < .01). All participants felt
      more comfortable and safer transferring from bed to wheelchair with the
      mechanical lift than with the gait belt (p < .01). Results are limited to normal
      weight patients but suggest that sit-stand lifts can be used in patients without
      upper extremity strength. Patients with limited weight-bearing capacity can be
      transferred by not raising them high in the lift. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27686536
TI  - Editorial Comment to Pathophysiology-based treatment of urolithiasis.

PMID- 27686537
TI  - Thermodynamics of Nanobody Binding to Lactose Permease.
AB  - Camelid nanobodies (Nbs) raised against the outward-facing conformer of a double
      Trp mutant of the lactose permease of Escherichia coli (LacY) stabilize the
      permease in outward-facing conformations. Isothermal titration calorimetry is
      applied herein to dissect the binding thermodynamics of two Nbs, one that
      markedly improves access to the sugar-binding site and another that dramatically
      increases the affinity for galactoside. The findings presented here show that
      both enthalpy and entropy contribute favorably to binding of the Nbs to wild-type
      (WT) LacY and that binding of Nb to double-Trp mutant G46W/G262W is driven by a
      greater enthalpy at an entropic penalty. Thermodynamic analyses support the
      interpretation that WT LacY is stabilized in outward-facing conformations like
      the double-Trp mutant with closure of the water-filled cytoplasmic cavity through
      conformational selection. The LacY conformational transition required for ligand
      binding is reflected by a favorable entropy increase. Molecular dynamics
      simulations further suggest that the entropy increase likely stems from release
      of immobilized water molecules primarily from the cytoplasmic cavity upon
      closure.

PMID- 27686535
TI  - Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer,
      and neurodegenerative disease.
AB  - In mammals, seven members of the sirtuin protein family known as class III
      histone deacetylase have been identified for their characteristic features. These
      distinguished characteristics include the tissues where they are distributed or
      located, enzymatic activities, molecular functions, and involvement in diseases.
      Among the sirtuin members, SIRT3 has received much attention for its role in
      cancer genetics, aging, neurodegenerative disease, and stress resistance. SIRT3
      controls energy demand during stress conditions such as fasting and exercise as
      well as metabolism through the deacetylation and acetylation of mitochondrial
      enzymes. SIRT3 is well known for its ability to eliminate reactive oxygen species
      and to prevent the development of cancerous cells or apoptosis. This review
      article provides a comprehensive review on numerous (noteworthy) molecular
      functions of SIRT3 and its effect on cancer cells and various diseases including
      Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease.

PMID- 27686539
TI  - [Prolonged cardiac monitoring guides the diagnosis and treatment of cryptogenic
      stroke].

PMID- 27686538
TI  - The effect of purmorphamine on differentiation of endometrial stem cells into
      osteoblast-like cells on collagen/hydroxyapatite scaffolds.
AB  - We assessed the effect of purmorphamine along with collagen/hydroxyapatite
      scaffold in inducing osteogenesis of human endometrial stem cells (hEnSCs). The
      adhesion, viability, proliferation, and differentiation of cells on scaffold were
      assayed with SEM, MTT, real time-PCR, and ALP assay, respectively. The results
      were shown good integration of cells with scaffold. Also, qRT-PCR of
      differentiated cells shows that osteoblast cell markers are expressed after 21d
      in 2D and scaffold groups while in the scaffold group the expression of these
      markers were higher than the 2D group. Based on our findings,
      collagen/hydroxyapatite scaffold with PMA has the potential role in osteogenic
      differentiation of hEnSCs.

PMID- 27686541
TI  - [Clinical application of multi-electrode synchronous radiofrequency ablation via
      switching controller for treating large hepatocellular carcinoma].
AB  - Objective: To explore the preliminary clinical efficacy and safety of multi
      electrode synchronous radiofrequency ablation via switching controller for
      treating large hepatocellular carcinoma. Methods: A total of 20 patients with
      large hepatocellular carcinoma from minimally invasive Interventional department
      of Sun Yat-sen University Cancer Center were enrolled in this retrospective study
      from December 2013 to December 2014.The procedures were conducted with multi
      electrode synchronous radiofrequency ablation via switching controller under CT
      guidance.The necrosis rate of tumor was assessed by the following imaging
      examination.The single factor analysis of variance (ANOVA) was employed to
      compare the total bilirubin, albumin, renal function, blood coagulation function
      before and after ablation, to evaluate the safety of treatment. Result: Twenty
      patients with a total of 31 lesions accepted 23 times ablation procedures using
      multi-electrode synchronous radiofrequency ablation via switching controller.The
      recent evaluation after treatment was as followed: complete necrosis rate 51.6%
      (16/31), nearly complete necrosis rate 22.6% (7/31), partial necrosis rate 9.7%
      (3/31), treatment effectiveness rate (necrosis rate > 50%) 83.9%.The necrosis
      rate which was less than half volume of the tumor was only seen in 5 cases with
      huge hepatocellular carcinoma (16.1%). No dead cases appeared after ablation
      procedures.The patients' total bilirubin elevated moderately after ablation
      procedures and reversed to normal level after liver function protection
      treatment.There were no statistical differences of renal function and blood
      coagulation function before and after ablation.After ablation procedures, 5 cases
      (21.7%, 5/23) appeared fever, 6 cases (26.1%) with vomiting, only 3 cases (13.0%,
      3/23) with moderately severe pain in 3 days after ablation and remitted after
      taking oral analgesics in one week. Conclusion: The clinical efficacy of multi
      electrode synchronous radiofrequency ablation via switching controller for large
      hepatocellular carcinoma is satisfactory with guaranteed security, which can be a
      choice for treating large hepatocellular carcinoma.

PMID- 27686540
TI  - [Clinical characteristics and associated risk factors of cytomegalovirus
      infection in patients with underlying systemic Rheumatic diseases].
AB  - Objective: To retrospectively investigate the clinical characteristics, risk
      factors of Cytomegalovirus (CMV) infection in patients with underlying rheumatic
      diseases. Methods: Clinical records of 263 rheumatic patients with or without CMV
      infection, hospitalized from March 2011 to June 2014 in Peking University
      People's Hospital, were analyzed.Clinical characteristics were summarized and
      compared in CMV positive and negative groups, to investigate the risk factors for
      CMV infection.Statistical analyses were conducted with SPSS 20.0 software.
      Results: A total of 62 rheumatic patients were found to have CMV infection, with
      48 regarded as CMV viremia, 7 diagnosed as CMV pneumonia, while the remaining 7
      suffered both CMV viremia and pneumonia.Eleven of 62 patients (17.7%) had a fatal
      outcome.Systemic lupus erythematosus (SLE) was the most commonly underlying
      disease (41.9%), followed by Sjogren syndrome (16.1%) and systemic vasculitis
      (12.9%). Lymphopenia and the reduction of CD4+ T lymphocytes, corticosteroids,
      cyclophosphamide (CTX) or mycophenolate mofetil (MMF), combined use of more than
      2 immunosuppressants and other severe underlying infections as risk factors for
      CMV infection in rheumatic patients.Meanwhile, the total dose of CTX wasn't
      different significantly between CMV positive and negative groups.Multivariate
      analysis revealed that large or pulsed dose of corticosteroids, combined use of
      immunosuppressants, and severe underlying infections remained independent risk
      factors for CMV infection. Conclusions: Lymphocytes, particularly the CD4+ T
      subsets, might play a vital role in the regulation and control of CMV
      infection.Other underlying infections, undergoing large dose corticosteroids
      therapy or combined use of immunosuppressants could be the risk factors for CMV
      infection in rheumatic patients.

PMID- 27686542
TI  - [Using 3.0 T MR to dynamically observe ablated lung tumors after percutaneous
      cryotherapy therapy].
AB  - Objective: To initially explore MRI features and its changing trends including of
      lung tumors after Argon-Helium cryoablation therapy, and enhance the recognition
      of MR findings of lung tumors postcryoablation. Methods: Twenty-three cases of
      patients with twenty six nodules of pulmonary malignance who received Argon
      Helium cryoablation therapy in Henan Cancer Hospital from July 2014 to January
      2016 were enrolled.All patients underwent unenhanced and dynamic contrast
      enhanced MRI scans at pre-and 1-day, 1-week, 1-, 3-, 6-, 12-month
      postcryoablation. Two radiologists independently reviewed MRI images, signal
      intensity in the ablated zone on T1WI and T2WI were assessed by a 5-point
      scale.The changing trends of size and signal intensity with time were showed by
      time-maximum diameter and time-score curve.Time-signal intensity curves based on
      dynamic enhanced sequence were also performed. Results: Typical MRI findings
      includes: heterogeneous signal intensity on both T1WI and T2WI at 1-day
      postcryoablation(26/26, 100%). Hyper-intense on T1WI(22/26, 84.6%) and
      T2WI(17/26, 65.4%) with a hypo-intense rim at 1-week postcryoablation.Decreasing
      signal intensity on T1WI(17/26, 65.4%) and increasing signal intensity on
      T2WI(22/26, 84.6%) at 1-month.Signal intensity declined to the level of muscle on
      both T1WI(18/26, 69.2%) and T2WI(19/26, 73.1%) at 3-month, nineteen ablated zone
      turned into patchy shape(19/26, 73.1%). The maximum diameter was largest at 1-day
      and gradually shrunk with time. The mean score value toped at 1-week and
      gradually decreased. A straight line type without definite enhancement was found
      from 1-day to 1-month postcryoablation, an inflow curve with a mild delayed
      enhancement was seen from 3- to 12- month. Totally 4 recurrence (4/26, 15.4%) all
      occurred at 3-month and were lack of a complete hypo-intense rim at 1-week
      postcryoablation. Conclusion: MRI findings of lung tumors postcryoablation are
      characteristic, a complete hypo-intense rim at 1-week is helpful to determine
      further recurrence, 1-week to 3-month is an important period to observe
      significant change of the ablation zone, MRI is valuable in identifying the
      ablation zone and can reflect its evolution with time.

PMID- 27686543
TI  - [Clinical value of changes of SUVmax in series 18F-FDG PET/CT imaging before and
      after chemotherapy for non-small cell lung cancer].
AB  - Objective: To evaluate the clinical value of changes of maximum standardized
      uptake value (SUVmax) in series 18F-FDG PET/CT imaging before and after
      chemotherapy for non-small cell lung cancer. Methods: From July 2008 to July
      2014, a total of 18 patients with pathological confirmed advanced NSCLC who
      received systemic chemotherapy were enrolled.18F-FDG PET/CT scans were performed
      before, 3-4 weeks after 2-4 cycles chemotherapy, 3-4 weeks after the end of
      chemotherapy for all patients, and added fourth scan for 3 patients 1 year
      later.The SUVmax of region of interesting was calculated.The histological
      diagnosis or clinical findings in a 36 months follow-up period served as the
      standard of control. Results: New metastases foci were found by 18F-FDG PET/CT
      scans before chemotherapy in 7 of 18 patients.The plans of chemotherapy for 5
      patients were changed as therapeutic responses were evaluated according to
      changes of SUVmax.Targeted therapy was added for 2 patients after the end of
      chemotherapy.There was a statistically significant difference in outcome of
      survival analysis between patients performed PET/CT scans and non-performed
      (P<0.05). Conclusion: Changes of SUVmax in series 18F-FDG PET/CT imaging before
      and after chemotherapy could be used to evaluate therapeutic response and
      effectively predict survival in patients with advanced NSCLC.

PMID- 27686544
TI  - [Association between polymorphism of ADAM33 gene and bronchial asthma in
      Mongolian population].
AB  - Objective: To investigate the different genotype and allele frequency
      distribution of ADAM33 gene T1, T2, V4, S2 sites Mongolian population, and
      discuss the relationship between ADAM33 gene polymorphism and bronchial asthma.
      Methods: From January 2014 to December 2015, a total of 180 cases of Mongolian
      patients with asthma were detected, compared with 186 cases of healthy Mongolian
      as controled and screening significant genes.Selected restriction fragment length
      polymorphism (PCR-RFLP) method to detected ADAM33 gene polymorphism.According to
      condition , the asthma group was divided into mild(n=83), medium group(n=47)and
      severe group(n=50). The distribution difference of different genotype and every
      genotype of V4 FEV1, eosinophils, IgE comparison were compared , and analysis
      their correlation. Results: In ADAM33 , the distribution of T1 sites (AA and AG
      genotypes) had statistical significance compared asthma group with control
      group(chi2=8.810, 8.294, P<0.05, OR=1.983, 0.500). The OR value of G allele was
      0.580.The distribution of S2 site(CC genotype) had statistical
      significance(chi2=4.277, P<0.05), the OR value of G allele was 1.423.the
      distribution of V4 sites (GC and GG genotypes) had statistical significance
      between the two groups (chi2=7.880, 10.313, P<0.05), OR value was 0.459, 2.130, G
      allele OR value was 1.496.The distribution frequency difference of each genotype
      in V4 sites in mild, medium and severe group was statistically significant
      (chi2=16.049, P<0.05), and compared various genotypes of FEV1, IgE, the
      difference was statistically significant (P<0.05), for each genotype of T2 site
      in asthma group and the control group there was no statistically significant in
      the distribution (chi2=1.218, 0.248, 1.287, P>0.05). Conclusions: T1, V4, S2
      locus polymorphism of ADAM33 gene may play a role in the Mongolian asthma
      population, and T2 locus polymorphism may has no relationship with Mongolian
      asthma patients.And the genotype polymorphism of V4 sites may be associated with
      asthma severity.

PMID- 27686545
TI  - [Correlation between post-stroke pneumonia and outcome in patients with acute
      brain infarction].
AB  - Objective: To investigate the correlation between post-stroke pneumonia and
      outcome in patients with acute brain infarction. Methods: Consecutive acute
      cerebral infarction patients who were hospitalized in Department of Neurology,
      Jinan Military General Hospital were prospectively recruited from August 2010 to
      August 2014. The baseline data including age, sex, the National Institute of
      Health Stroke Scale (NIHSS) scores, type of Oxfordshire Community Stroke Project
      (OCSP: total anterior circulation infarct, partial anterior circulation infarct,
      posterior circulation infarct and lacunar infarct), fasting blood glucose etc.
      after admission were recorded. Post-stroke pneumonia was diagnosed by treating
      physician according to criteria for hospital-acquired pneumonia of the Centers
      for Disease Control and Prevention. Recovery was assessed by modified Rankin
      Scale (mRS) 180 days after stroke by telephone interview (mRS<=2 reflected good
      prognosis, and mRS>2 reflected unfavorable prognosis). Multinominal Logistic
      regression analysis, Kaplan-Meier curve and log rank test were used. Results: A
      total of 1 249 patients were enrolled, among them 173 patients were lost during
      follow-up. A total of 159 patients had post-stroke pneumonia, while 1 090
      patients were without post-stroke. Compared with patients without post-stoke
      pneumonia, patients with post-stroke pneumonia were older (67+/-13 vs 63+/-12
      years, P=0.000), more severe (NIHSS, 15(14) vs 4(4), P=0.000). Compared with
      patients without post-stoke pneumonia, more patients with post-stroke pneumonia
      suffered from heart failure (12.58% vs 3.40%, P=0.000), atrial fibrillation
      (26.42% vs 8.81%, P=0.000), myocardial infarction (10.06% vs 5.05%, P=0.016),
      recurrent brain infarction (30.19% vs 22.66%, P=0.045), total anterior
      circulation infarct type of OCSP (46.54% vs 19.63%, P=0.000), posterior
      circulation infarct of OCSP (39.62% vs 25.51%, P=0.001); more patients suffered
      from disorder of consciousness (60.38% vs 9.27%, P=0.000), dysphagia (34.59% vs
      19.89%, P=0.000), vomiting (26.42% vs 8.81%, P=0.000), aphasia (35.85% vs 16.61%,
      P=0.000) since onset. The morbidity of post-stroke pneumonia among patients with
      unfavorable outcome (29.37%(111/378)) was significantly higher than that among
      patients with favorable outcome (3.73%(26/698)) (P=0.000). Post-stroke pneumonia
      was an independent prognostic factor for long-term unfavorable outcome (OR=2.414,
      95%CI: 1.336-4.361, P=0.004) and long-term mortality (OR=2.132, 95%CI: 1.229
      3.699, P=0.007). According Kaplan-Meier estimation, the cumulative 180 days
      survival of patients with post-stroke pneumonia was lower than those without post
      stroke pneumonia (62.04%(85/137) vs 93.29%(876/939)); Log-rank test: chi2=137.32,
      P=0.000. Conclusions: Acute brain infarction patients with post-stroke pneumonia
      are older, more severe; more suffering from heart failure, atrial fibrillation,
      myocardial infarction; more suffering from disorder of consciousness since onset.
      Post-stroke pneumonia is an independent prognostic factor for long-term
      unfavorable outcome and for long term mortality in patients with acute brain
      infarction.

PMID- 27686546
TI  - [The surgical strategy of microsurgical treatment for fulminant hemorrhagic
      dilation of the fourth ventricle].
AB  - Objective: To investigate the effectiveness and advantage of improved
      microsurgery for fulminant hemorrhagic dilation of the fourth ventricle. Methods:
      The clinical data of 21 patients with fulminant hemorrhagic dilation of the
      fourth ventricle were analyzed retrospectively.All patients underwent hemorrhage
      evacuation and improved atlantooccipital decompression via middle suboccipital
      trans-cerebellar vermis approach, with preceding external ventricular drain.
      Results: One patient died of brainstem failure postoperative, and 20 patients
      were followed up from 6 to 17 months.There were 8 patients whose KPS exceeded 90,
      6 patients whose KPS were 60 to 90, 4 patients whose KPS were 30 to 60, and two
      patients whose KPS were lower than 30.There was no recurrence of hydrocephalus
      and posterior fossa fluid. Conclusions: The improved microsurgery for fulminant
      hemorrhagic dilation of the fourth ventricle not only could effectively raise the
      success rate of salvage, but also greatly reduce postoperative complications
      compared with traditional mode.

PMID- 27686547
TI  - [Direct anterior approach versus posterolateral approach for total hip
      arthroplasty in the lateral decubitus position].
AB  - Objective: To compare the clinical efficacy of the direct anterior approach (DAA)
      and the posterolateral approach (PLA) for total hip arthroplasty (THA) in the
      lateral decubitus position. Methods: From July to December, 2014, 104 patients
      randomly divided into two equal groups of the DAA group and the PLA group
      underwent unilateral primary THA procedures.All procedures were performed by the
      same surgeon in the Department of Orthopaedics, the Affiliated Anhui Provincial
      Hospital of Anhui Medical University.General data, perioperative index,
      postoperative function and radiological evaluation were recorded and
      statistically analyzed. Results: The patients had an average follow-up of 14
      (range, 10-16) months.No significant differences were detected with respect to
      the operation time, incision length, preoperative Hb concentration and
      transfusion rate between two groups (P> 0.05 for all comparisons). However, there
      were significant differences associated with the intraoperative bleeding,
      postoperative drainage and postoperative Hb concentration in the two
      groups(P<0.05 for all comparisons). The DAA group showed significant superior
      outcomes compared with the PLA group in the Harris hip scores [(83.6+/-7.1) vs
      (79.8+/-6.6), P<0.05], WOMAC[ (28.9+/-6.1) vs (36.1+/-6.9), P<0.001], and VAS
      pain scores[ (2.2+/-0.9) vs (2.9+/-1.1), P<0.05]at 1 month after surgery. No
      differences were seen between the study groups in the evaluation of radiography
      and the incidence of adverse event (P> 0.05 for all comparisons). Conclusions:
      Compared with the posterolateral approach, the present study shows the exciting
      results in patients underwent the DAA THA in the lateral decubitus position at
      early follow-up.The advantages of THA using the DAA include less operative
      trauma, alleviation of postoperative pain, and faster postoperative
      rehabilitation. It is a safe, reliable and effective surgery approach.

PMID- 27686548
TI  - [Assessment for pain control efficiency of ultrasound guided adductor canal block
      in total knee arthroplasty: a report of 28 continuous cases].
AB  - Objective: To assess the pain control efficiency of continuous adductor canal
      block in total knee arthroplasty. Methods: From October to December 2015,
      patients with severe knee osteoarthritis undergoing primary unilateral TKA were
      observed clinically.All of the patients received ultrasound-guided continuous
      adductor canal block after surgery.NPRS Pain score in rest and activity at 2, 6,
      12, 24, 48 h after surgery were collected, preoperative and postoperative
      quadriceps strength at 24, 48 h were analyzed. Opioids consumption and anesthesia
      related adverse effects were also recorded. Results: All of the patients were
      enrolled. Rest pain control was fairly good(1.8+/-1.5), (2.4+/-1.5), (2.7+/-1.3),
      (2.7+/-1.7), (2.3+/-1.4) score, but the patients were not satisfied with activity
      pain control(3.1+/-2.1), (3.1+/-2.1), (4.2+/-2.2), (4.7+/-2.5), (6.2+/-2.4)
      score. There were statistically differences comparing the NPRS in rest pain with
      the score in activity, except for the results between each other at 6 hours
      (P=0.252>0.05)after surgery.The results showed no significant differences
      comparing quadriceps strengthpreoperatively with 24, 48 h postoperatively by
      repeated measurements variance analysis.Eight patients acquired additional use of
      dolantin once (100 mg/per time) within 24 h and among them three patients
      acquired once dolantin during 24 to 48 h. Eleven patients complained nausea
      postoperatively, one reported vomiting and one experienced xerostomia.
      Conclusion: Ultrasound-guided continuous adductor canal block can reduce resting
      pain after TKA, but has a limited effect in activity pain control.Quadriceps
      strength had been spared after ACB, which might performearly benefits in
      rehabilitation. ACB-related complications need further observation to be defined.

PMID- 27686549
TI  - [The Study of relationship between fetal radius loss and chromosomal
      abnormality].
AB  - Objective: To explore the relationship between fetal radius loss and chromosomal
      abnormalities. Methods: Collect data of 3 100 cases pregnant women who had been
      checked in the second hospital of Jilin University from 2012 to 2015.There were 8
      cases of absent radius, except 1 case of fetal lost follow-up, the remaining 7
      cases had complete ultrasound, chromosome examination and the result of
      induction.The relationship between fetal radius loss and chromosomal
      abnormalities were analysed. Results: There were 1 case of 21 trisomy syndrome, 1
      case of trisomy 13 syndrome, 2 cases of trisomy 18, 2 cases of chromosome
      translocation, 1 case of normal chromosome result and 1 case was lost to follow
      up of the 8 absent radius fetuses. Conclusion: Through a comparison between the
      chromosome and ultrasonic characteristics of fetuses who have absent radius, we
      had indicated the relationship of fetal radius deletion and chromosomal anomaly,
      improved the positive rate of chromosome invasion examination, and provided the
      reference for eugenics.

PMID- 27686550
TI  - [Comparison of radiofrequency catheter ablation for paroxysmal supraventricular
      tachycardia guided by three dimensional navigation with X-ray].
AB  - Objective: To compare the therapeutic efficiency and safety of radiofrequency
      catheter ablation (RFCA) for paroxysmal ventricular tachycardia (PSVT) guided by
      three-dimensional navigation with X-ray. Methods: One hundred and seventy-six
      patients with PSVT hospitalized in Department of Cardiology, Zhejiang Provincial
      People's Hospital between January 2013 and December 2014 were enrolled in this
      study. RFCA was performed on 95 patients (Group A) guided by the three
      dimensional electric-field navigation system (NavX) and the procedures were done
      with the spatial localization method, unless X-ray was needed in some
      cases.Eighty-one patients (Group B) underwent RFCA guided by X-ray only.The
      success rate, complications, recurrence rate, operation time, and X-ray exposure
      were compared between the two groups. Results: The immediate success rate of
      operation was 100% in the 176 PSVT patients without complications.There were
      recurrences in 2 cases of Group A, while in 1 case of Group B. The average
      operation time in Group A was (97+/-20) min, while (91+/-26) min in Group B. The
      median X-ray fluoroscopy time was 3.0 min and radiation dose was 18.5 MUGym2 in
      Group A, which were significantly reduced compared with those in Group B (34.5
      min, 167.3 MUGym2) (P<0.05). There was no significant difference in immediate
      procedure success rate, complications, recurrence, and operative time between
      this two groups (P>0.05). Conclusions: The RFCA for PSVT guided by three
      dimensional navigation is safe and feasible in the experienced
      electrophysiological center.Most patients suffer less or no X-ray radiation.

PMID- 27686551
TI  - [Preliminary study on assessment of lexiscan-induced blood-brain barrier opening
      and its level by CT perfusion imaging].
AB  - Objective: To evaluate the level of lexiscan-induced blood-brain barrier opening
      of healthy rabbits via CT perfusion weighted imaging (PWI) scan. Methods: Between
      November 2014 and May 2015, thirty New Zealand white rabbits were randomly
      assigned into three groups: the experimental group A1 which received one
      injection of lexiscan(1 ml/kg); the experimental group A2 which received three
      times injection of lexiscan(total dose: 1.5 ml/kg), finished within 15 minutes;
      the control group B which was injected the same volume normal saline(1 ml/kg),
      after 30 minutes, CT PWI scan was performed. Then cerebral blood flow (CBF),
      cerebral blood volume (CBV), mean transit time (MTT) and permeability surface(PS)
      of the region of interest of each group were acquired and compared statistically.
      Five cases of each group were injected with 2% Evans blue intravenously posterior
      to imaging. After one hour of infusion, all the animals were killed. Their brains
      were examined for the determination of Evans blue distribution. Results: Both the
      values of CBF and CBV and the staining with Evans blue of the group A1(CBF:
      (89.88+/-2.21), (81.42+/-4.28) ml.(100 g)-1.min-1; CBV: (3.97+/-0.43), (3.66+/
      0.16) ml/g)and group A2 (CBF: (75.16+/-0.84), (63.66+/-7.21) ml.(100 g)-1.min-1;
      CBV: (4.07+/-0.01), (3.75+/-0.05) ml/g) were higher than those of the group
      B(CBF: (20.08+/-5.08), (14.58+/-8.62) ml.(100 g)-1.min-1; CBV: (0.85+/-0.04),
      (0.65+/-0.17) ml/g), the differences were all statistically significant (all
      P<0.01). While there was no statistically difference between group A1 and group
      A2(P>0.05). The value of PS of the group A2((22.43+/-8.09), (20.20+/-7.01)ml.(100
      g)-1.min-1 )was higher than that of group A1((13.82+/-4.44), (10.12+/
      2.44)ml.(100 g)-1.min-1) and group B(0.00, 0.00)(the lowest one), the differences
      were all statistically significant(all P<0.01). The value of MTT of the group
      A1((2.50+/-0.82, 2.47+/-0.10) s) had no statistical difference with group A2 and
      group B, while the value of group A2((4.50+/-0.17), (4.72+/-0.15) s) was higher
      than that of group B((1.88+/-0.09), (1.99+/-0.00) s), the differences were all
      statistically significant (P<0.05). Conclusion: Changes in hemodynamics of
      lexiscan-induced blood-brain barrier opening can be monitored by CT PWI scan.
      When the total dose of lexiscan increasing, the level of the BBB opening is
      higher with significantly increased CBF, CBV, PS and MTT.

PMID- 27686552
TI  - [Effects of body mass index on blood pressure control rate in elderly coronary
      heart disease outpatients with hypertension].
AB  - Objective: To explore the influences of body mass index (BMI) on blood pressure
      control rate in elderly coronary heart disease (CHD) outpatients with
      hypertension. Methods: In this multicenter, non-intervention and cross-sectional
      survey, the elderly coronary heart disease patients with hypertension aged 60
      years or over were recruited from 165 hospitals in 21 provinces or cities across
      China from April to July 2011, and 5 140 cases of elderly CHD patients with
      hypertension were finally included into the study. The cases were divided into
      low BMI group (n=130 cases), normal body mass index (BMI) group (n=1 390 cases),
      overweight (n=2 418 cases), obesity group (n=662 cases) according to the
      different levels of BMI. Clinical data and blood pressure control rate were
      compared among the groups, and relationships of different BMI levels with blood
      pressure control rate were analyzed by the binary classification unconditioned
      Logistic regression equation. Results: There was a statistically significant
      difference in blood pressure control rate of general population, men and women
      patients among low BMI group, normal BMI group, overweight and obesity group
      (chi2=66.346, 58.995, 26.044, respectively, P<0.001), blood pressure failure rate
      in obesity group (73.7%) was higher than that in overweight group (65.8%) and
      normal BMI group (57.5%) (P<0.05), and overweight group was also higher than
      normal BMI group (P<0.05); blood pressure failure rate in obesity men was higher
      than that in normal BMI and low BMI group (P<0.05), overweight group was higher
      than normal BMI group (P<0.05); blood pressure failure rate in obesity women was
      higher than that in normal BMI and low BMI group (P<0.05). There was a
      statistically significant difference in blood pressure control rate of different
      age groups (60-70, 71-80, >80 years old) among low BMI group, normal BMI group,
      overweight and obesity group (chi2=37.729, 20.007, 15.538, respectively,
      P<0.001). Blood pressure failure rate in obesity patients with 60-70 years old
      was higher than that in overweight and normal BMI group (P<0.05), blood pressure
      failure rates in obesity and overweight patients with 71-80 and > 80 years old
      were also higher than those in normal BMI group (P<0.05). Multivariable Logistic
      regression equation showed that overweight in overall population (OR=1.313, 95%CI
      1.170-1.731, P<0.05), obesity (OR=2.295, 95%CI 2.295-1.496, P<0.05) were
      independent risk factors for blood pressure failure rate, in addition, obesity
      was also risk factor for blood pressure failure rate in men and women patients.
      Conclusions: Increased BMI has an adverse effect on blood pressure control rate
      in elderly CHD outpatients with hypertension, and may be the independent risk for
      blood pressure failure rate in those patients. Much more attention should be
      given to control BMI level so as to increase the blood pressure success rate and
      improve the patients' prognosis.

PMID- 27686553
TI  - MYC amplification in angiosarcomas arising in the setting of chronic lymphedema
      of morbid obesity.
AB  - BACKGROUND: Angiosarcoma is a malignancy of vascular endothelial cells which may
      arise secondarily as a complication of lymphedema, including chronic lymphedema
      of morbid obesity. Amplifications in MYC are frequently present in secondary
      angiosarcoma (arising in irradiated sites and chronic lymphedema) and less
      frequently in primary cutaneous angiosarcoma. OBJECTIVE: To describe the presence
      of MYC amplifications in two cases of cutaneous angiosarcoma secondary to chronic
      lymphedema of morbid obesity. METHODS: This study is a case series of two
      patients with cutaneous angiosarcoma. Clinical data was retrieved from the
      medical records. Histopathological analysis of the biopsy specimens was
      performed, including immunohistochemistry, along with fluorescence in situ
      hybridization. RESULTS: Angiosarcoma arose in the setting of massive chronic
      lymphedema complicating morbid obesity without other predisposing risk factors.
      Both cases exhibited epithelioid cell morphology and high-level MYC
      amplification. CONCLUSION: We report MYC amplification in two cases of
      angiosarcoma arising in massive chronic lymphedema of morbid obesity.

PMID- 27686554
TI  - The value of time-to-onset in statistical signal detection of adverse drug
      reactions: a comparison with disproportionality analysis in spontaneous reports
      from the Netherlands.
AB  - PURPOSE: In pharmacovigilance, the commonly used disproportionality analysis
      (DPA) in statistical signal detection is known to have its limitations. The aim
      of this study was to investigate the value of the time to onset (TTO) of ADRs in
      addition to DPA. METHODS: We performed a pilot study using individual case safety
      reports (ICSRs) for three drugs (Cervarix(r), nitrofurantoin and simvastatin)
      from the Lareb spontaneous reporting database. TTO distributions for drug - ADR
      associations were compared to other ADRs for the same drug and to other drugs for
      the same ADR using two-sample Anderson-Darling testing. Statistically significant
      associations were considered true positive (TP) signals if the association was
      present in the official product information of the drug. Sensitivity and
      specificity for the TTO method were compared with the DPA method. As a measure of
      disproportionality, the reporting odds ratio (ROR) was used. RESULTS: In general,
      sensitivity was lower, and specificity was higher for the TTO method compared to
      DPA. The TTO method showed similar sensitivity for all three drugs, whereas
      specificity was lower for Cervarix(r). Eight additional TP signals were found
      using the TTO method compared to DPA. CONCLUSIONS: Our study shows that
      statistical signal detection based on the TTO alone resulted in a limited number
      of additional signals compared to DPA. We therefore conclude that the TTO method
      is of limited value for full database statistical screening in our setting.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27686555
TI  - Women have higher rates of mental disorders than men, NHS survey finds.

PMID- 27686556
TI  - A meta-analysis for echocardiographic assessment of right ventricular structure
      and function in ARVC.
AB  - INTRODUCTION: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an
      inherited pathology that can increase the risk of sudden death. Current Task
      Force Criteria for echocardiographic diagnosis do not include new, regional
      assessment tools which may be relevant in a phenotypically diverse disease. We
      adopted a systematic review and meta-analysis approach to highlight
      echocardiographic indices that differentiated ARVC patients and healthy controls.
      METHODS: Data was extracted and analysed from prospective trials that employed a
      case-control design meeting strict inclusion and exclusion as well as a-priori
      quality criteria. Structural indices included proximal RV outflow tract(RVOT1)
      and RV diastolic area(RVDarea). Functional indices included RV fractional area
      change (RVFAC), Tricuspid Annular Systolic Excursion(TAPSE), peak systolic and
      early diastolic myocardial velocities (S' and E' respectively) and myocardial
      strain. RESULTS: Patients with ARVC had larger RVOT1 (mean ? SD; 34 vs. 28 mm
      P<0.001) and RVDarea (23 vs. 18 cm2 P<0.001) compared to healthy controls. ARVC
      patients also had lower RVFAC (38 vs. 46 % P<0.001), TAPSE(17 vs. 23 mm P<0.001),
      S' (9 vs. 12 cm.s-1 P<0.001), E' (9 vs. 13 cm.s-1 P<0.001) and myocardial strain
      (-17 vs. -30% P<0.001). CONCLUSION: The data from this meta-analysis support
      current Task Force criteria for the diagnosis of ARVC. In addition, other RV
      measures that reflect the complex geometry and function in ARVC clearly
      differentiated between ARVC and healthy controls and may provide additional
      diagnostic and management value. We recommend that future working groups consider
      this data when proposing new / revised criteria for the echocardiographic
      diagnosis of ARVC.

PMID- 27686557
TI  - Paratesticular Rhabdomyosarcoma Associated with Tuberculosis.
AB  - We report a 16-year-old male patient diagnosed with paratesticular
      rhabdomyosarcoma and mediastinal tuberculous lymphadenitis. The differential
      diagnosis between high or early stage of rhabdomyosarcoma and tuberculosis (TB)
      was critical in this patient without a history of TB. Unexpected
      lymphadenopathies detected during the staging of patients with malignancy should
      be carefully evaluated, and TB should be taken into consideration in the
      differential diagnosis especially in underdeveloped and developing countries.
      Unnecessary additional treatments increase the rate of mortality and morbidity
      because of upstaging of cancer. Further, TB reactivation can be seen during
      chemotherapy because of immunosuppression.

PMID- 27686558
TI  - Prediction of Bronchial Mucus Plugs Formation in Patients with Refractory
      Mycoplasma Pneumoniae Pneumonia.
AB  - Background: We aimed to find the relationship between the clinical
      characteristics and mucus plug formation and developed models to predict mucus
      plug formation in refractory Mycoplasma pneumoniae pneumonia (RMPP) infection.
      Methods: RMPP patients treated with bronchoscopy were retrospectively enrolled in
      the study between November 2011 and November 2015. Multivariate logistic
      regression was performed to identify independent predictors of mucus plug
      formation. Results: Of the 173 RMPP patients enrolled, the mucus plug group
      accounted for 82 (47.4%) cases. Multivariate logistic regression analysis
      identified age, fever duration, C-reactive protein (CRP) and lactic dehydrogenase
      (LDH) as independent risk factors for mucus plug. We assigned one point for age,
      length of fever and CRP and two points for LDH. Using this predicted score, we
      identified patients with mucus plug with 71.8% sensitivity and 78.9% specificity.
      Conclusions: Our predictive models based on demographic and laboratory variables
      accurately predicted mucus plug formation in initial treatment of patients with
      RMPP.

PMID- 27686560
TI  - Theoretical insights into the stabilities, detonation performance, and
      electrostatic potentials of cocrystals containing alpha- or beta-HMX and TATB,
      FOX-7, NTO, or DMF in various molar ratios.
AB  - A molecular dynamics method was employed to study the binding energies associated
      with the cocrystallization (at selected crystal planes) of either 1,3,5-triamino
      2,4,6-trinitro-benzene (TATB), 1,1-diamino-2,2-dinitroethylene, 3-nitro-1,2,4
      triazol-5-one (TATB, FOX-7, and NTO, respectively, all of which are explosives),
      or N,N-dimethylformamide (DMF, a nonenergetic solvent) in various molar ratios
      with 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane in its alpha and beta
      conformations (alpha-HMX and beta-HMX, respectively). The results showed that the
      cocrystals with low molar ratios (2:1, 1:1, 1:2, and 1:3) were the most stable.
      The binding energies of HMX/NTO and HMX/DMF were larger than those of HMX/TATB
      and HMX/FOX-7. According to the calculated stabilities, HMX prefers to adopt its
      alpha form in HMX/TATB and its beta form in HMX/NTO, whereas the two forms
      coexist in HMX/FOX-7. For HMX/TATB, HMX/NTO, and alpha-HMX/FOX-7, increasing the
      proportion of the cocrystal component with the highest detonation heat (HMX in
      the first two cases, FOX-7 in the latter) increases the detonation heat,
      velocity, and pressure of the cocrystal. However, increasing the proportion of
      the component with the highest detonation heat in beta-HMX/FOX-7 and gamma-CL
      20/FOX-7 increases the detonation heat of the cocrystal but decreases its
      detonation velocity. An investigation of the surface electrostatic potential
      revealed how the sensitivity changes upon cocrystal formation. Graphical Abstract
      Surface electrostatic potential of HMX/TATB.

PMID- 27686559
TI  - Evaluating genomic DNA extraction methods from human whole blood using endpoint
      and real-time PCR assays.
AB  - The extraction of genomic DNA is the crucial first step in large-scale
      epidemiological studies. Though there are many popular DNA isolation methods from
      human whole blood, only a few reports have compared their efficiencies using both
      end-point and real-time PCR assays. Genomic DNA was extracted from coronary
      artery disease patients using solution-based conventional protocols such as the
      phenol-chloroform/proteinase-K method and a non-phenolic non-enzymatic Rapid
      Method, which were evaluated and compared vis-a-vis a commercially available
      silica column-based Blood DNA isolation kit. The appropriate method for
      efficiently extracting relatively pure DNA was assessed based on the total DNA
      yield, concentration, purity ratios (A260/A280 and A260/A230), spectral profile
      and agarose gel electrophoresis analysis. The quality of the isolated DNA was
      further analysed for PCR inhibition using a murine specific ATP1A3 qPCR assay and
      mtDNA/Y-chromosome ratio determination assay. The suitability of the extracted
      DNA for downstream applications such as end-point SNP genotyping, was tested
      using PCR-RFLP analysis of the AGTR1-1166A>C variant, a mirSNP having
      pharmacogenetic relevance in cardiovascular diseases. Compared to the traditional
      phenol-chloroform/proteinase-K method, our results indicated the Rapid-Method to
      be a more suitable protocol for genomic DNA extraction from human whole blood in
      terms of DNA quantity, quality, safety, processing time and cost. The Rapid
      Method, which is based on a simple salting-out procedure, is not only safe and
      cost-effective, but also has the added advantage of being scaled up to process
      variable sample volumes, thus enabling it to be applied in large-scale
      epidemiological studies.

PMID- 27686561
TI  - Benchmarking the DFT methodology for assessing antioxidant-related properties:
      quercetin and edaravone as case studies.
AB  - The overall objective was to identify an accurate computational electronic method
      to virtually screen phenolic compounds through their antioxidant and free-radical
      scavenging activity. The impact of a key parameter of the density functional
      theory (DFT) approach was studied. Performances of the 21 most commonly used
      exchange-correlation functionals are thus detailed in the evaluation of the main
      energetic parameters related to the activities of two prototype antioxidants,
      namely quercetin and edaravone, is reported. These functionals have been chosen
      among those belonging to three different families of hybrid functionals, namely
      global, range separated, and double hybrids. Other computational parameters have
      also been considered, such as basis set and solvent effects. The selected
      parameters, namely bond dissociation enthalpy (BDE), ionization potential (IP),
      and proton dissociation enthalpy (PDE) allow a mechanistic evaluation of the
      antioxidant activities of free radical scavengers. Our results show that all the
      selected functionals provide a coherent picture of these properties, predicting
      the same order of BDEs and PDEs. However, with respect to the reference values,
      the errors found at CBS-Q3 level significantly vary with the functional. Although
      it is difficult to evidence a global trend from the reported data, it clearly
      appears that LC-omegaPBE, M05-2X, and M06-2X are the most suitable approaches for
      the considered properties, giving the lowest cumulative mean absolute errors.
      These methods are therefore suggested for an accurate and fast evaluation of
      energetic parameters related to an antioxidant activity via free radical
      scavenging.

PMID- 27686562
TI  - Protonation and electronic structure of 2,6-dichlorophenolindophenolate during
      reduction. A theoretical study including explicit solvent.
AB  - Protonation in the two-electron/two-proton reduction processes of 2,6
      dichlorophenolindophenolate (DCIP) is investigated combining density functional
      theory (DFT) and molecular dynamics (MD) methods. DCIP (anion), DCIP*- (radical
      anion), and DCIP2- (dianion) are considered, including the electronic structure
      analysis from the prospective of quantum theory of atoms and molecules (QTAIM).
      It is shown that oxygen on the indophenolate moiety and nitrogen are the first
      and/or the second proton acceptor sites and their energetic order depends on the
      total charge of the system. MD simulations of differently charged species
      interacting with the solvent molecules have been performed for methanol, water,
      and oxonium cation (H3O+). Methanol and water molecules are found to form only
      hydrogen bonds with the solute irrespective of its charge. The calculated pKa
      values show that the imino group of DCIPH- is a weaker acid than water. While in
      the case of DCIP (and DCIP*-) plus oxonium cation, proton transfer from the
      solvent to the solute was evidenced for both aforementioned acceptor sites. In
      addition, MD simulations of bulks containing 15 and 43 molecules of water around
      the DCIP molecule have been performed, revealing the formation of 2-4 hydrogen
      bonds. Graphical Abstract 2,6-Dichlorophenolindophenolate interacts with solvent
      molecules (water, oxonium cation and methanol). Hydrogen transfer and electronic
      structure are studied by DFT and molecular dynamics methods.

PMID- 27686565
TI  - Evolving Surgical Interventions in the Treatment of Glaucoma.
AB  - Interventions in the treatment of mild to moderate glaucoma have evolved to
      include a group of procedures collectively named "Minimally Invasive Glaucoma
      Surgery (MIGS)." These procedures are less invasive than traditional filtering
      surgery and setons and offer the benefit of an improved side-effect profile. A
      review of current published literature has shown that these procedures offer
      lower intraocular pressure, decrease reliance on topical medications, have no
      negative effect on refractive outcomes, and can be safely done following failed
      tube surgery.

PMID- 27686563
TI  - Neuroinflammatory component of gray matter pathology in multiple sclerosis.
AB  - OBJECTIVE: In multiple sclerosis (MS), using simultaneous magnetic resonance
      positron emission tomography (MR-PET) imaging with 11 C-PBR28, we quantified
      expression of the 18kDa translocator protein (TSPO), a marker of activated
      microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white
      matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo
      pathological and clinical relevance of neuroinflammation. METHODS: Fifteen
      secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS)
      patients, and 14 matched healthy controls underwent 11 C-PBR28 MR-PET. MS
      subjects underwent 7T T2*-weighted imaging for cortical lesion segmentation, and
      neurological and cognitive evaluation. 11 C-PBR28 binding was measured using
      normalized 60- to 90-minute standardized uptake values and volume of distribution
      ratios. RESULTS: Relative to controls, MS subjects exhibited abnormally high 11 C
      PBR28 binding across the brain, the greatest increases being in cortex and
      cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed
      relatively modest TSPO increases. With the exception of cortical lesions, where
      TSPO expression was similar, 11 C-PBR28 uptake across the brain was greater in
      SPMS than in RRMS. In MS, increased 11 C-PBR28 binding in cortex, deep GM, and
      NAWM correlated with neurological disability and impaired cognitive performance;
      cortical thinning correlated with increased thalamic TSPO levels. INTERPRETATION:
      In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and
      NAWM, is closely linked to poor clinical outcome, and is at least partly linked
      to neurodegeneration. Distinct inflammatory-mediated factors may underlie
      accumulation of cortical and WM lesions. Quantification of TSPO levels in MS
      could prove to be a sensitive tool for evaluating in vivo the inflammatory
      component of GM pathology, particularly in cortical lesions. Ann Neurol
      2016;80:776-790.

PMID- 27686564
TI  - Theorizing epigenesis in a time of preexistence: From the end of the seventeenth
      century to the 1720s.
AB  - According to a classic periodization in the history of science, biological
      thought as it emerged in France from the last decades of the seventeenth century
      to the 1740s was strongly committed to the doctrine of the preexistence of germs.
      Nicolas Malebranche's role in disseminating this paradigm, particularly in the
      milieu of the Academie Royale des Sciences during the years when Bernard Le
      Bouyer de Fontenelle was its secretary, has been studied in detail, especially by
      Jacques Roger. However, much less has been said about the authors who argued
      against this doctrine prior to the appearance of the relevant pieces by Pierre
      Louis Moreau de Maupertuis, Georges-Louis Leclerc, Comte de Buffon, and Denis
      Diderot. I aim to examine a series of French medical treatises and clandestine
      manuscripts that outlined a mechanist theory of epigenesis, between the end of
      the seventeenth century and the 1720s, to bring to light the strategies-often
      quite original-that allowed them to achieve this result. One interesting case is
      the heterodox readers of Malebranche, which use some of his own arguments
      (notably on the physiology of brain traces and the laws of nature) both against
      preexistence and to support epigenesis. I inquire into the historical worth of
      the positions defended by these authors as well as into the connections existing
      between the history of epigenesis and that of materialism in the early modern
      era.

PMID- 27686566
TI  - Low-tube-voltage selection for triple-rule-out CTA: relation to patient size.
AB  - OBJECTIVES: To investigate the relationship between image quality and patient
      size at 100 kilovoltage (kV) compared to 120 kV ECG-gated Triple-Rule-Out CT
      angiography (TRO-CTA). METHODS: We retrospectively included 73 patients (age 64
      +/- 14 years) who underwent retrospective ECG-gated chest CTA. 40 patients were
      scanned with 100 kV while 33 patients with 120 kV. Body mass index (BMI),
      patients' chest circumference (PC) and thoracic surface area (TSA) were recorded.
      Quantitative image quality was assessed as vascular attenuation in the ascending
      aorta (AA), pulmonary trunk (PA) and left coronary artery (LCA) and the signal-to
      noise ratio (SNR) in the AA. RESULTS: There was no significant difference in BMI
      (26.0 +/- 4.6 vs. 28.0 +/- 6.7 kg/m2), PC (103 +/- 7 vs. 104 +/- 10 cm2) and TSA
      (92 +/- 15 vs. 91 +/- 19 cm2) between 100 kV and 120 kV group. Mean vascular
      attenuation was significantly higher in the 100 kV compared to the 120 kV group
      (AA 438 vs. 354 HU, PA 460 vs. 349 HU, LCA 370 vs. 299 HU all p < 0.001). SNR was
      not significantly different, even after adjusting for patient size. Radiation
      dose was significantly lower in the 100 kV group (10.7 +/- 4.1 vs. 20.7 +/- 10.7
      mSv; p < 0.001). CONCLUSIONS: 100 kV TRO-CTA is feasible in normal-to-overweight
      patients while maintaining image quality and achieving substantial dose
      reduction. KEY POINTS: * 100 kV protocols result in a significantly lower
      radiation dose. * Mean vascular attenuation is significantly higher using 100 kV.
      * SNR and CNR are not significantly different between 100 kV and 120 kV. * 100 kV
      CTA is feasible regardless of patient size while maintaining image quality.

PMID- 27686567
TI  - Anaplastic lymphoma kinase positive large B-cell lymphoma: Literature review and
      report of an endoscopic fine needle aspiration case with tigroid backgrounds
      mimicking seminoma.
AB  - Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare
      distinct type of non-Hodgkin's lymphoma that arises in association with
      alterations of the ALK gene. This distinct disease entity is typically associated
      with an aggressive clinical course and appears in light microscopic preparations
      as a monomorphic population of large, immunoblast-like cells. In this report, we
      describe a case of ALK+ LBCL diagnosed by transgastric endoscopic ultrasound
      guided fine needle aspiration (EUS FNA) of splenic hilar lymph nodes. Modified
      Giemsa stained direct smears from the FNA sample demonstrated large lesional
      cells with foamy cytoplasm and macronucleoli admixed with small lymphocytes in
      tigroid backgrounds, mimicking the cytologic appearance of seminoma. Ancillary
      immunohistochemical studies subsequently confirmed the diagnosis of ALK+ LBCL
      with the lesional cells being immunoreactive for CD138, VS38c, MUM1, ALK1, and
      lambda light chain. The cohesiveness of the cells, the cellular morphology, and
      the tigroid backgrounds were all pitfalls for accurate diagnosis of this rare
      specific type of lymphoid malignancy by cytology. To our knowledge this is the
      first case report detailing the diagnosis of ALK+ LBCL by EUS FNA and the first
      report describing a glycogen-rich tigroid background in direct FNA smears.
      Establishing a refined diagnosis in cases of this rare form of LBCL is necessary,
      as therapies targeting ALK may be of value in clinical management. Diagn.
      Cytopathol. 2017;45:148-155. (c) 2016 Wiley Periodicals, Inc.

PMID- 27686568
TI  - Expressions of vaginal endothelial nitric oxide synthase and phosphodiesterase 5
      in female sexual dysfunction: a pilot study.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to investigate the expression of
      endothelial nitric oxide synthase (eNOS) and phosphodiesterase (PDE) 5 in vaginal
      tissue of premenopausal women experiencing stress urinary incontinence (SUI) with
      and without sexual dysfunction. METHODS: Women presenting for treatment of SUI
      were screened using the Female Sexual Function Index (FSFI) and 10 were selected
      who met the criteria for female sexual dysfunction (FSD) and 10 asymptomatic
      controls. Vaginal tissue specimens were obtained from those premenopausal women
      aged >=40 years who had had sexual activity >=2 times every month for the last 6
      months and who were scheduled to undergo surgery for SUI. FSD criteria was FSFI
      scores <18 and arousal domain scores <3. The control group had FSFI scores >=26
      and individual domain scores >=4. The expressions of eNOS and PDE 5 were compared
      in the two groups using immunofluorescence staining and western blotting.
      RESULTS: The mean total FSFI scores were 30.4 +/- 2.6 and 15.3 +/- 2.3 in the
      control and FSD groups respectively. In immunofluorescence staining, eNOS and
      PDE5 were localized in the vaginal epithelium. In western blotting, the
      expressions of eNOS and PDE5 were significantly lower in the FSD group than in
      the control group (p = 0.003 and p = 0.038 respectively). CONCLUSIONS: eNOS and
      PDE5 in the vagina may play important roles in the pathophysiology of FSD.

PMID- 27686569
TI  - Five years after midurethral sling surgery for stress incontinence: obesity
      continues to have an impact on outcomes.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the impact of
      preoperative body mass index >=30 on objective and subjective cure rates 5 years
      after midurethral sling surgery. METHODS: Secondary analysis of the 5-year
      results of a randomized clinical trial evaluating tension-free vaginal tape vs
      transobturator tape surgery. Women (n = 176) were classified as obese or non
      obese based on preoperative height and weight. Women self-reported symptoms and
      quality of life, and underwent standardized physical examinations and pad
      testing. Categorical data were analyzed using Chi-squared or Fisher's exact
      tests, continuous data by Mann-Whitney U test. Primary outcome was objective cure
      defined as <1 g urine lost on pad-test at 5 years post-surgery. Secondary
      outcomes were subjective cure of incontinence, urinary urge incontinence
      symptoms, and quality of life scores. RESULTS: Non-obese women had a higher rate
      of objective cure, 87.4 % (n = 83 out of 95) compared with 65.9 % (n = 29 out of
      44) in the obese group (P = 0.003, risk difference [RD] 21.5 %, 95 % CI 5.9-37.0
      %). Subjectively, non-obese women also reported higher rates of cure, 76.7 % (n =
      89 out of 116) compared with 53.6 % (n = 30 out of 56) of obese women (P = 0.002,
      RD 23.2 %, 95 % CI 8.0-38.3 %). Overall rates of urge incontinence symptoms were
      similar in the two groups, but rates of bothersome symptoms were higher for obese
      women (58.9 % vs 42.1 %, P = 0.039, RD 16.8 % 95 % CI 1.1-32.6). CONCLUSIONS:
      Five years after surgery, obese women continued to experience lower rates of cure
      compared with non-obese women.

PMID- 27686571
TI  - Physical exercise induces structural alterations in the hippocampal astrocytes:
      exploring the role of BDNF-TrkB signaling.
AB  - While it has been known that physical activity can improve cognitive function and
      protect against neurodegeneration, the underlying mechanisms for these protective
      effects are yet to be fully elucidated. There is a large body of evidence
      indicating that physical exercise improves neurogenesis and maintenance of
      neurons. Yet, its possible effects on glial cells remain poorly understood. Here,
      we tested whether physical exercise in mice alters the expression of trophic
      factor-related genes and the status of astrocytes in the dentate gyrus of the
      hippocampus. In addition to a significant increase in Bdnf mRNA and protein
      levels, we found that 4 weeks of treadmill and running wheel exercise in mice,
      led to (1) a significant increase in synaptic load in the dentate gyrus, (2)
      alterations in astrocytic morphology, and (3) orientation of astrocytic
      projections towards dentate granule cells. Importantly, these changes were
      possibly linked to increased TrkB receptor levels in astrocytes. Our study
      suggests that astrocytes actively respond and could indeed mediate the positive
      effects of physical exercise on the central nervous system and potentially
      counter degenerative processes during aging and neurodegenerative disorders.

PMID- 27686570
TI  - A thicker intima-media carotid wall was found in a cohort of children with recent
      onset migraine.
AB  - AIM: Migraine affects approximately 10-20% of the general population, including
      children and adolescents, and an association between migraine and increased risks
      for cardiovascular disease and stroke have been reported in adult patients. This
      study aimed to address the lack of data on children with migraine. METHODS: This
      study comprised 30 children and adolescents (16 male) with migraine. We evaluated
      their biochemical profile, glucose homeostasis, vascular function by flow
      mediated dilatation and arterial structure by carotid intima-media thickness
      (cIMT). A group of 32 age, sex and auxologically matched children (17 male)
      served as controls. RESULTS: The group of children with migraine had a normal
      biochemical profile and glucose homeostasis, but presented with significantly
      thicker cIMT than the control group (0.48 +/- 0.07 mm versus 0.45 +/- 0.04, p <
      0.05). CONCLUSION: We observed a significantly thicker cIMT in children with
      migraine compared with the controls. The brief time interval between the onset of
      the disease and the time of the study makes it unlikely that repetitive migraine
      attacks could be responsible for the thickening of the cIMT. Thus, it may be
      speculated that primitive vascular function abnormalities were wholly or partly
      responsible for the development of migraine in this paediatric cohort.

PMID- 27686572
TI  - Fractures of the axis: a review of pediatric, adult, and geriatric injuries.
AB  - Fractures of the second cervical vertebra (C2, axis) are common in adult spine
      surgery. Those fractures occurring in younger adult patients are often associated
      with high-energy mechanism trauma, resulting in a "Hangman's Fracture."
      Management of these fractures is often successful with nonoperative means, though
      surgery may be needed in those fractures with greater displacement and injury to
      the C2-C3 disc. Older patients are more likely to sustain fractures of the
      odontoid process. The evidence supporting surgical management of these fractures
      is evolving, as there may be a mortality benefit to surgery. Regardless of
      treatment, longer-term mortality rates are high in this patient population, which
      should be discussed with the patient and family at the time of injury. Pediatric
      patients may suffer fractures of the axis, though differentiation of normal and
      pathologic findings is necessary and more difficult with the skeletally immature
      spine.

PMID- 27686573
TI  - Knowledge is power: Issues of measuring training and performance in cycling.
AB  - Mobile power meters provide a valid means of measuring cyclists' power output in
      the field. These field measurements can be performed with very good accuracy and
      reliability making the power meter a useful tool for monitoring and evaluating
      training and race demands. This review presents power meter data from a Grand
      Tour cyclist's training and racing and explores the inherent complications
      created by its stochastic nature. Simple summary methods cannot reflect a
      session's variable distribution of power output or indicate its likely metabolic
      stress. Binning power output data, into training zones for example, provides
      information on the detail but not the length of efforts within a session. An
      alternative approach is to track changes in cyclists' modelled training and
      racing performances. Both critical power and record power profiles have been used
      for monitoring training-induced changes in this manner. Due to the inadequacy of
      current methods, the review highlights the need for new methods to be established
      which quantify the effects of training loads and models their implications for
      performance.

PMID- 27686574
TI  - Coronary Physiology Assessment for the Diagnosis and Treatment of Stable Ischemic
      Heart Disease.
AB  - Coronary artery disease is the most prevalent cardiovascular disease in the USA.
      In the majority of settings, percutaneous coronary intervention (PCI) for stable
      coronary artery disease (CAD) reduces angina and improves quality of life;
      however, it does not improve survival and is associated with infrequent but
      serious complications. Selection of appropriate patients and coronary lesions for
      revascularization with PCI is crucial to maximize the benefit-to-risk ratio. The
      assessment of the hemodynamic significance of intermediate coronary lesions has
      been shown to improve outcomes and reduce healthcare costs. The current review
      summarizes the existing evidence regarding the physiological assessment of
      coronary lesions, with emphasis on fractional flow reserve, the most common
      invasive hemodynamic assessment modality.

PMID- 27686575
TI  - Knowledge and attitude of parents/caregivers towards hearing loss and screening
      in newborns - a systematic review.
AB  - OBJECTIVE: The parents/caregivers of a newborn play a pivotal role in the process
      of hearing screening and intervention. The decisions taken by them depend on
      their knowledge and attitude. The purpose of this study was to review the
      literature systematically on knowledge and attitude of parents/caregivers towards
      infant hearing loss and newborn hearing screening. DESIGN: A systematic search
      was conducted using electronic databases for the periods from 1990 to March 2016.
      Two authors scrutinized the studies and extracted the data based on predetermined
      criteria. STUDY SAMPLE: Ten studies. RESULTS: Ear discharge was correctly
      identified as a risk factor for hearing loss along with measles,
      drugs/medication, family history, congenital causes and noise exposure. The
      studies revealed mixed results for knowledge about newborn hearing screening.
      Overall, the parents/caregivers showed positive attitudes towards hearing
      screening and intervention options. However, due to heterogeneity in the studies,
      it's hard to derive a conclusion. CONCLUSIONS: The present review sheds light on
      the common areas of misconception among parents/caregivers about risk factors of
      infant hearing loss and newborn hearing screening. The review also draws
      attention to the need to have more studies exploring this knowledge and attitude
      of parents/caregivers among diverse populations.

PMID- 27686576
TI  - Modulation of inflammation and disease tolerance by DNA damage response pathways.
AB  - The accurate replication and repair of DNA is central to organismal survival.
      This process is challenged by the many factors that can change genetic
      information such as replication errors and direct damage to the DNA molecule by
      chemical and physical agents. DNA damage can also result from microorganism
      invasion as an integral step of their life cycle or as collateral damage from
      host defense mechanisms against pathogens. Here we review the complex crosstalk
      of DNA damage response and immune response pathways that might be evolutionarily
      connected and argue that DNA damage response pathways can be explored
      therapeutically to induce disease tolerance through the activation of tissue
      damage control processes. Such approach may constitute the missing pillar in the
      treatment of critical illnesses caused by multiple organ failure, such as sepsis
      and septic shock.

PMID- 27686577
TI  - Biparental chloroplast inheritance leads to rescue from cytonuclear
      incompatibility.
AB  - Although organelle inheritance is predominantly maternal across animals and
      plants, biparental chloroplast inheritance has arisen multiple times in the
      angiosperms. Biparental inheritance has the potential to impact the evolutionary
      dynamics of cytonuclear incompatibility, interactions between nuclear and
      organelle genomes that are proposed to be among the earliest types of genetic
      incompatibility to arise in speciation. We examine the interplay between
      biparental inheritance and cytonuclear incompatibility in Campanulastrum
      americanum, a plant species exhibiting both traits. We first determine patterns
      of chloroplast inheritance in genetically similar and divergent crosses, and then
      associate inheritance with hybrid survival across multiple generations. There is
      substantial biparental inheritance in C. americanum. The frequency of biparental
      inheritance is greater in divergent crosses and in the presence of cytonuclear
      incompatibility. Biparental inheritance helps to mitigate cytonuclear
      incompatibility, leading to increased fitness of F1 hybrids and recovery in the
      F2 generation. This study demonstrates the potential for biparental chloroplast
      inheritance to rescue cytonuclear compatibility, reducing cytonuclear
      incompatibility's contribution to reproductive isolation and potentially slowing
      speciation. The efficacy of rescue depended upon the strength of incompatibility,
      with a greater persistence of weak incompatibilities in later generations. These
      findings suggest that incompatible plastids may lead to selection for biparental
      inheritance.

PMID- 27686578
TI  - Domestic work division and satisfaction in cohabiting adults: Associations with
      life satisfaction and self-rated health.
AB  - BACKGROUND: The amount and perception of domestic work may affect satisfaction
      with everyday life, but further knowledge is needed about the relationship
      between domestic work division and health and well-being. AIM: To describe the
      division of, and satisfaction with, domestic work and responsibility for
      home/family in adults living with a partner. A further aim was to investigate the
      associations between these aspects and self-rated life satisfaction and health.
      METHOD: Data from the Work, Lipids and Fibrinogen survey collected 2009 were
      used, comprising 4924 participants living with a partner. Data were analyzed
      using logistic regression. RESULTS: The majority shared domestic work and
      responsibility for home/family equally with their partner. However, more women
      conducted the majority of the domestic work and were less satisfied with its
      division. When both division and satisfaction with division was included in the
      analysis, solely satisfaction with the division and the responsibility were
      associated with higher odds for good life satisfaction. Regarding health, higher
      odds for good self-rated health were seen in those who were satisfied with their
      division of responsibility. CONCLUSION AND SIGNIFICANCE: The results highlight
      the importance of taking into account not solely the actual division of domestic
      work but also the satisfaction with it.

PMID- 27686579
TI  - A case report of a deep surgical site infection with Terrisporobacter
      glycolicus/T. Mayombei and review of the literature.
AB  - BACKGROUND: There are increasing data regarding Terrisporobacter glycolicus as an
      emerging anaerobic pathogen. However, the few published cases to date usually
      report it as part of a polymicrobial infection. Here, we describe the first
      reported monomicrobial surgical site infection with this bacterium.
      Identification methods, taxonomy, and clinical management of this rarely
      identified pathogen are also discussed. CASE PRESENTATION: A previously healthy
      66-year-old sustained an open olecranon fracture of his left arm after trauma. He
      subsequently underwent open reduction and internal fixation (ORIF), with
      insertion of an olecranon locking plate and two locking screws. Ten days after
      surgery, the patient developed increasing pain at the surgical site and noted
      green discharge from the wound. Culture of the wound discharge yielded grew a
      pure Gram-positive anaerobe identified by the RapidANA(r) microbial
      identification system as C. difficile (profile 000010, 99.1 % probability).
      Reference laboratory testing identified the isolate as T. glycolicus/mayombei
      (previously designated as Clostridium glycolicum/mayombei) by 16S rRNA gene
      sequencing and as Clostridium glycolicum by MALDI-TOF mass spectrometry. The
      patient received an 8-week course of moxifloxacin and metronidazole with an
      excellent clinical response at 12 months' follow-up. CONCLUSIONS: We describe the
      case of a deep surgical site infection with T. glycolicus/mayombei (formerly
      known as Clostridium glycolicum and Clostridium mayombei, respectively), which
      extends our knowledge of the clinical spectrum of this pathogen. The isolate was
      misidentified by phenotypic identification methods.

PMID- 27686580
TI  - Modelling drug flux through microporated skin.
AB  - A simple mathematical equation has been developed to predict drug flux through
      microporated skin. The theoretical model is based on an approach applied
      previously to water evaporation through leaf stomata. Pore density, pore radius
      and drug molecular weight are key model parameters. The predictions of the model
      were compared with results derived from a simple, intuitive method using porated
      area alone to estimate the flux enhancement. It is shown that the new approach
      predicts significantly higher fluxes than the intuitive analysis, with transport
      being proportional to the total pore perimeter rather than area as intuitively
      anticipated. Predicted fluxes were in good general agreement with experimental
      data on drug delivery from the literature, and were quantitatively closer to the
      measured values than those derived from the intuitive, area-based approach.

PMID- 27686581
TI  - Temperature responsive porous silicon nanoparticles for cancer therapy -
      spatiotemporal triggering through infrared and radiofrequency electromagnetic
      heating.
AB  - : One critical functionality of the carrier system utilized in targeted drug
      delivery is its ability to trigger the release of the therapeutic cargo once the
      carrier has reached its target. External triggering is an alluring approach as it
      can be applied in a precise spatiotemporal manner. In the present study, we
      achieved external triggering through the porous silicon (PSi) nanoparticles (NPs)
      by providing a pulse of infrared or radiofrequency radiation. The NPs were
      grafted with a temperature responsive polymer whose critical temperature was
      tailored to be slightly above 37 degrees C. The polymer coating improved the
      biocompatibility of the NPs significantly in comparison with their uncoated
      counterparts. Radiation induced a rapid temperature rise, which resulted in the
      collapse of the polymer chains facilitating the cargo release. Both infrared and
      radiofrequency radiation were able to efficiently trigger the release of the
      encapsulated drug in vitro and induce significant cell death in comparison to the
      control groups. Radiofrequency radiation was found to be more efficient in vitro,
      and the treatment efficacy was verified in vivo in a lung carcinoma (3LL) mice
      model. After a single intratumoral administration of the carrier system combined
      with radiofrequency radiation, there was clear suppression of the growth of the
      carcinoma and a prolongation of the survival time of the animals. TOC IMAGE: The
      temperature responsive (TR) polymer grafted on the surface of porous silicon
      nanoparticles (PSi NPs) changes its conformation in response to the heating
      induced by infrared or radiofrequency radiation. The conformation change allows
      the loaded doxorubicin to escape from the pores, achieving controlled drug
      release from TR PSi NPs, which displayed efficacy against malignant cells both in
      vitro and in vivo.

PMID- 27686582
TI  - Intracellular delivery and ultrasonic activation of folate receptor-targeted
      phase-change contrast agents in breast cancer cells in vitro.
AB  - Breast cancer is a diverse and complex disease that remains one of the leading
      causes of death among women. Novel, outside-of-the-box imaging and treatment
      methods are needed to supplement currently available technologies. In this study,
      we present evidence for the intracellular delivery and ultrasound-stimulated
      activation of folate receptor (FR)-targeted phase-change contrast agents (PCCAs)
      in MDA-MB-231 and MCF-7 breast cancer cells in vitro. PCCAs are lipid-coated,
      perfluorocarbon-filled particles formulated as nanoscale liquid droplets capable
      of vaporization into gaseous microbubbles for imaging or therapy. Cells were
      incubated with 1:1 decafluorobutane (DFB)/octafluoropropane (OFP) PCCAs for 1h,
      imaged via confocal microscopy, exposed to ultrasound (9MHz, MI=1.0 or 1.5), and
      imaged again after insonation. FR-targeted PCCAs were observed intracellularly in
      both cell lines, but uptake was significantly greater (p<0.001) in MDA-MB-231
      cells (93.0% internalization at MI=1.0, 79.5% at MI=1.5) than MCF-7 cells (42.4%
      internalization at MI=1.0, 35.7% at MI=1.5). Folate incorporation increased the
      frequency of intracellular PCCA detection 45-fold for MDA-MB-231 cells and 7-fold
      for MCF-7 cells, relative to untargeted PCCAs. Intracellularly activated PCCAs
      ranged from 500nm to 6MUm (IQR=800nm-1.5MUm) with a mean diameter of 1.15+/-0.59
      (SD) microns. The work presented herein demonstrates the feasibility of PCCA
      intracellular delivery and activation using breast cancer cells, illuminating a
      new platform toward intracellular imaging or therapeutic delivery with
      ultrasound.

PMID- 27686583
TI  - High intensity focused ultrasound hyperthermia for enhanced macromolecular
      delivery.
AB  - Mild hyperthermia has been used in combination with polymer therapeutics to
      further increase delivery to solid tumors and enhance efficacy. An attractive
      method for generating heat is through non-invasive high intensity focused
      ultrasound (HIFU). HIFU is often used for ablative therapies and must be adapted
      to produce uniform mild hyperthermia in a solid tumor. In this work a magnetic
      resonance imaging guided HIFU (MRgHIFU) controlled feedback system was developed
      to produce a spatially uniform 43 degrees C heating pattern in a subcutaneous
      mouse tumor. MRgHIFU was employed to create hyperthermic conditions that enhance
      macromolecular delivery. Using a mouse model with two subcutaneous tumors, it was
      demonstrated that MRgHIFU enhanced delivery of both Evans blue dye (EBD) and
      Gadolinium-chelated N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. The EBD
      accumulation in the heated tumors increased by nearly 2-fold compared to unheated
      tumors. The Gadolinium-chelated HPMA copolymers also showed significant
      enhancement in accumulation over control as evaluated through MRI T1-mapping
      measurements. Results show the potential of HIFU-mediated hyperthermia for
      enhanced delivery of polymer therapeutics.

PMID- 27686584
TI  - Necrobiosis Lipoidica.

PMID- 27686585
TI  - Congenital Anorectal Malformation Severity Does Not Predict Severity of
      Congenital Heart Defects.
AB  - OBJECTIVE: To determine the prevalence of congenital heart defects (CHDs) in
      patients with mild or severe congenital anorectal malformations (CARMs), and
      whether all patients with CARM need pediatric cardiology screening. STUDY DESIGN:
      We included 129 patients with CARM born between 2004 and 2013, and referred to
      University Medical Center Groningen. Recto-perineal and recto-vestibular fistulas
      were classified as mild CARMs, all others as severe. Significant patent foramen
      ovale, secundum atrial septal defect, and small ventricular septum defect were
      classified as minor CHDs, all others as major. RESULTS: Of 129 patients with
      CARM, 67% had mild CARM, 33% severe CARM, and 17% were additionally diagnosed
      with CHD. CHDs were distributed equally in patients with mild or severe CARMs.
      Patients with multiple congenital abnormalities were more frequently diagnosed
      with CHD (n = 16, 36%) than patients without multiple congenital malformations (n
      = 5, 9%, P = .001). Patients with CARM diagnosed with CHD using pediatric cardiac
      echo screening were younger than 3 months of age at diagnosis. Earlier general
      pediatric examinations missed 7 (50%) children with mild and 4 (50%) with severe
      CHDs. CONCLUSIONS: The severity of CARM could predict neither prevalence nor
      severity of CHD. More than one-half of CHDs were missed during the first physical
      examination. No new CHDs were found in patients older than 3 months of age at the
      time CARMs were diagnosed. We recommend screening all patients with CARM younger
      than 3 months of age for CHD at the time CARM is diagnosed. Preoperative
      echocardiography should be the rule in children younger than 3 months of age and
      with multiple congenital anomalies.

PMID- 27686586
TI  - Cesarean Delivery, Overweight throughout Childhood, and Blood Pressure in
      Adolescence.
AB  - OBJECTIVES: To investigate whether children delivered by cesarean had a higher
      risk of being overweight from early until late childhood and whether they had a
      higher blood pressure in adolescence compared with children delivered vaginally.
      STUDY DESIGN: We used data from a Dutch birth cohort study with prenatal
      inclusion in 1996 and 1997. Mode of delivery (cesarean or vaginal delivery) was
      ascertained at 3 months after birth by questionnaire. During clinical
      examinations, height and weight (at age 4, 8, 12, and 16 years) and blood
      pressure (at age 12 and 16 years) were measured. We used mixed model analysis to
      estimate associations of cesarean delivery with overweight and blood pressure z
      scores in 2641 children who participated in at least 1 of the 4 examinations.
      RESULTS: Children born by cesarean delivery (n = 236, 8.9%) had a 1.52 (95% CI
      1.18, 1.96) higher odds of being overweight throughout childhood than children
      delivered vaginally. Children born by cesarean delivery had no higher systolic
      blood pressure z-score (0.11 SD, 95% CI -0.04, 0.26), nor a different diastolic
      blood pressure z-score (-0.00 SD, 95% CI -0.10, 0.09) in adolescence than
      children delivered vaginally. CONCLUSIONS: Compared with children delivered
      vaginally, children delivered by cesarean had a 52% higher risk of being
      overweight throughout childhood, but this was not accompanied by a higher blood
      pressure in adolescence.

PMID- 27686587
TI  - Risk of recurrence after a first unprovoked seizure in children.
AB  - OBJECTIVES: This study aimed to evaluate the first episode of unprovoked
      epileptic seizure in children and assess recurrence risk factors. METHODS: This
      was a retrospective observational study, based on the analysis of medical records
      of patients admitted between 2003 and 2014, with first epileptic seizure, at the
      pediatric service of a secondary hospital. The data were analyzed using the SPSS
      20.0 program. RESULTS: Of the 103 patients, 52.4% were boys. The median age at
      the first seizure was 59 (1-211) months. About 93% of children were submitted to
      an electroencephalogram at the first episode and 47% underwent neuroimaging
      assessment. Treatment with an antiepileptic drug was started in 46% of patients.
      The recurrence rate was 38% and of these, 80% had the second seizure within six
      months after the first event. Of the assessed risk factors, there was a
      statistically significant association between seizure during sleep and recurrence
      (p=0.004), and between remote symptomatic etiology seizure and occurrence of new
      seizure (p=0.02). The presence of electroencephalogram abnormalities was also
      associated with the occurrence of new seizures (p=0.021). No association was
      found between age, duration of the seizure, and family history of epilepsy with
      increased risk of recurrence. CONCLUSIONS: Most children with a first unprovoked
      epileptic seizure had no recurrences. The risk of recurrence was higher in
      patients with seizure occurring during sleep or remote symptomatic ones and those
      with abnormal electroencephalogram results.

PMID- 27686588
TI  - Influence of the informal primary caretaker on glycemic control among prepubertal
      pediatric patients with type 1 diabetes mellitus.
AB  - OBJECTIVES: In prepubertal type 1 diabetic patients (DM1), the availability of an
      informal primary caregiver (ICP) is critical to making management decisions; in
      this study, the ICP-related risk factors associated with glycemic control were
      identified. PATIENTS, MATERIALS, AND METHODS: A comparative cross-sectional study
      was performed. Fifty-five patients with DM1 under the age of 11 years were
      included. The patient-related factors associated with glycemic control evaluated
      were physical activity, DM1 time of evolution, and adherence to medical
      indications. The ICP-related factors evaluated were education, employment
      aspects, depressive traits (Beck questionnaire), family functionality (family
      APGAR), support of another person in patient care, stress (Perceived Stress
      Scale), and socioeconomic status (Bronfman questionnaire). Multivariate logistic
      and linear regression analyses were performed. RESULTS: The patients' median age
      was 8 years; 29 patients had good glycemic control, and 26 were uncontrolled. The
      main risk factor associated with glycemic dyscontrol was stress in the ICP (OR
      24.8; 95% CI 4.06-151.9, p=0.001). While, according to the linear regression
      analysis it was found that lower level of education (beta 0.991, 95% CI 0.238
      1.743, p=0.011) and stress (beta 1.918, 95% CI 1.10-2.736, p=0.001) in the ICP,
      as well as family dysfunction (beta 1.256, 95% CI 0.336-2.177, p=0.008) were
      associated with higher levels of glycated hemoglobin. CONCLUSIONS: Level of
      education and stress in the ICP, as well as family dysfunction, are factors that
      influence the lack of controlled blood glucose levels among prepubertal DM1
      patients.

PMID- 27686590
TI  - Pseudo-tying injuries in a hanged person.
AB  - A 50-year-old man was found hanged on the concrete dam of a water reservoir. The
      ligature, a braided rope made of synthetic fibres, was attached to a lamp on the
      dam crest. The length of the rope between the fastening point and the noose was
      about 4m. At autopsy, stretchmark-like intimal tears of the carotid arteries were
      found, but the full pattern of (internal) decapitation and severance of the
      cervical spine was not present. The right wrist showed two almost circular,
      ribbon-like abrasions initially suggesting that the man had been tied before
      hanging. When the ligature was examined, horny scales adhered to the noose, but
      were also detected away from the slip-knot. By means of a DNA analysis the
      epidermal traces could be assigned to the deceased. The overall picture of the
      findings suggested that the man had roped down from the dam crest with the
      ligature wrapped around his right wrist thus abrading the skin.

PMID- 27686591
TI  - A radiation oncologist's guide to contour the parotid gland.

PMID- 27686592
TI  - Boost delineation in breast radiation therapy: Isotropic versus anisotropic
      margin expansion.
AB  - PURPOSE: The purpose of this article is to compare isotropic and anisotropic
      margin expansion with regard to the size of the clinical target volume boost
      (CTVboost) and the interobserver variability (IOV). METHODS AND MATERIALS:
      Lumpectomy cavities marked with 3 or more surgical clips were delineated by 6
      radiation oncologists who specialized in breast radiation therapy. CTVboost
      anisotropic was created by manually expanding the tumor bed with an anisotropic
      margin of 15 mm (20 mm in case of extensive intraductal component) minus the
      surgical free margins in 6 directions (anteroposterior, craniocaudal, and
      superoinferior). For the CTVboost isotropic, the tumor bed was enlarged with an
      isotropic margin of 15 mm (20 mm in case of extensive intraductal component)
      minus the minimal surgical free margin. The volumes of the delineated CTVboost
      (cm3) were measured. To assess the IOV, the Jaccard index (JI), defined as the
      intersection divided by the size of the union of the sample sets, was used (ideal
      value = 1). The JI was calculated for each case and each observer pair. Linear
      mixed models were used for all analyses. RESULTS: A total of 444 delineated tumor
      beds were evaluated. The mean volume of the CTVboost almost doubled by expanding
      the tumor bed with an isotropic margin compared with anisotropic margins
      (CTVboost isotropic 94 mL [12.5-331.0] vs CTVboost anisotropic 50 mL [3.2-332.7];
      P = .0006). The IOV, assessed by the JI, significantly decreased by using
      isotropic versus anisotropic margin expansion (JICTV boost isotropic 0.73 [0.02
      0.92] vs JICTV boost anisotropic 0.51 [0.0-0.8]; P< .0001). Because of the known
      positive correlation of the IOV and larger volumes, we corrected for CTVboost
      volumes. With this correction, the difference in IOV remains highly significant
      (P < .0001) in favor of isotropic margin expansion. CONCLUSIONS: The use of
      anisotropic margin expansion from tumorbed to CTVboost isotropic significantly
      reduced the volume of the delineated CTVboost with a factor of 1.9 compared with
      isotropic margin expansion, but it substantially increased the interobserver
      variability.

PMID- 27686594
TI  - Simultaneous removal of carbon and nitrogen by mycelial pellets of a
      heterotrophic nitrifying fungus-Penicillium sp. L1.
AB  - A novel heterotrophic nitrifying fungus, defined as Penicillium sp. L1, can form
      mycelial pellets in liquid medium in this study. The effects of inoculation
      method, C/N ratio, initial pH, and temperature were gradually evaluated to
      improve the simultaneous removal of total nitrogen (TN) and chemical oxygen
      demand (COD) in wastewater by Penicillium sp. L1. Results showed that compared
      with spore inoculation, 48 h pellet inoculum could significantly increase the
      pellet size (from about 1.5 mm to 3.2 mm) and improve the removal capability,
      particularly for COD removal (from less than 50-86.20%). The removal efficiencies
      of TN and COD reached 98.38% (from 136.01 mg/L to 2.20 mg/L) and 92.40% (from
      10,720 mg/L to 815 mg/L) under the following conditions: C/N 36, pH 3, 30 degrees
      C, and inoculation with 48 h pellets. The pellet diameter reached 4.8 mm after 4
      day cultivation. In this case, Penicillium sp. L1 removed TN from 415.93 mg/L to
      43.39 mg/L, as well as COD from 29,533 mg/L to 8850 mg/L. Overall, the results
      indicated that the pellet size was closely related to the pollutant-removal
      ability of Penicillium sp. L1. Furthermore, mycelial pellets (4.8 mm, dead) only
      adsorbed 38.08% TN (from 125.45 mg/L to 77.78 mg/L), which indicated that
      adsorption did not play a major role in the nitrogen-removal process.

PMID- 27686593
TI  - From pathogenesis to clinical application: insights into exosomes as transfer
      vectors in cancer.
AB  - Exosomes are nanoscale extracellular membrane vesicles that are created by the
      fusion of an intracellular multivesicular body with the cell membrane. They are
      widely distributed in serum, urine, saliva and other biological fluids. As
      important transfer vectors for intercellular communication and genetic material,
      exosomes can stimulate target cells directly via receptor-mediated interactions
      or via the transfer of various bioactive molecules, such as cell membrane
      receptors, proteins, mRNAs and microRNAs, thus exerting their biological
      functions. This review focuses on the biological characteristics of exosomes, as
      well as their role and underlying mechanisms of action in the evolution of tumor
      formation, metastasis, drug resistance and other malignant behaviors.
      Additionally, this review emphasizes the potential applications of exosomes in
      the treatment of tumors. Further research may provide new ideas and methods to
      establish effective, exosome-based strategies for the early diagnosis and
      treatment of tumors.

PMID- 27686595
TI  - Low-density lipoprotein transport through an arterial wall under hypertension - A
      model with time and pressure dependent fraction of leaky junction consistent with
      experiments.
AB  - The influence of hypertension on low-density lipoproteins intake into the
      arterial wall is an important factor for understanding mechanisms of
      atherosclerosis. It has been experimentally observed that the increased pressure
      leads to the higher level of the LDL inside the wall. In this paper we attempt to
      construct a model of the LDL transport which reproduces quantitatively
      experimental outcomes. We supplement the well-known four-layer arterial wall
      model to include two pressure induced effects: the compression of the intima
      tissue and the increase of the fraction of leaky junctions. We demonstrate that
      such model can reach the very good agreement with experimental data.

PMID- 27686596
TI  - Allometric scaling of electrical excitation and propagation in the mammalian
      heart.
AB  - Variations in body mass impose constraints on the structure and function of
      mammalian species, including those of the cardiovascular system. Numerous
      biological processes, including cardiovascular parameters, have been shown to
      scale with body mass (BM) according to the law of allometric scaling: Y=Y =a?BMb
      (Y, biological process; a, normalization constant; b, scaling exponent, which in
      many instances is a multiple of 1/4). These parameters include heart and
      breathing rates, intervals and subintervals of the electrocardiogram (ECG),
      action potential duration (APD), metabolic rate, and temporal properties of
      ventricular fibrillation. For instance, the hierarchical branching networks of
      the vascular system, and of the specialized conduction system in the heart have
      been proposed to be important determinants of allometric scaling. A global and
      unifying molecular mechanism of allometric scaling has not been put forth, but
      changes in gene expression have been proposed to play an important role. Even
      though it is accepted that differences in body size have cardiovascular effects,
      the use of scaling in the clinical setting is limited. An increase in the
      clinical utilization of scaling is thought to lead to improved cardiovascular
      disease diagnosis and management in patients.

PMID- 27686597
TI  - PARP inhibitors and stratified treatment of prostate cancer.

PMID- 27686599
TI  - Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix
      mineral composition or maturation.
AB  - Intermittent administration of parathyroid hormone (PTH) is used to stimulate
      bone formation in patients with osteoporosis. A reduction in the degree of matrix
      mineralisation has been reported during treatment, which may reflect either
      production of undermineralised matrix or a greater proportion of new matrix
      within the bone samples assessed. To explore these alternatives, high resolution
      synchrotron-based Fourier Transform Infrared Microspectroscopy (sFTIRM) coupled
      with calcein labelling was used in a region of non-remodelling cortical bone to
      determine bone composition during anabolic PTH treatment compared with region
      matched samples from controls. 8week old male C57BL/6 mice were treated with
      vehicle or 50MUg/kg PTH, 5 times/week for 4weeks (n=7-9/group). Histomorphometry
      confirmed greater trabecular and periosteal bone formation and 3-point bending
      tests confirmed greater femoral strength in PTH-treated mice. Dual calcein labels
      were used to match bone regions by time-since-mineralisation (bone age) and
      composition was measured by sFTIRM in six 15MUm2 regions at increasing depth
      perpendicular to the most immature bone on the medial periosteal edge; this
      allowed in situ measurement of progressive changes in bone matrix during its
      maturation. The sFTIRM method was validated in vehicle-treated bones where the
      expected progressive increases in mineral:matrix ratio and collagen crosslink
      type ratio were detected with increasing bone maturity. We also observed a
      gradual increase in carbonate content that strongly correlated with an increase
      in longitudinal stretch of the collagen triple helix (amide I:amide II ratio).
      PTH treatment did not alter the progressive changes in any of these parameters
      from the periosteal edge through to the more mature bone. These data provide new
      information about how the bone matrix matures in situ and confirm that bone
      deposited during PTH treatment undergoes normal collagen maturation and normal
      mineral accrual.

PMID- 27686600
TI  - Variants of HSD11B2 gene in hypertensive disorders of pregnancy.
AB  - INTRODUCTION: One of the hypotheses concerning the etiology of gestational
      hypertension (GH) and pre-eclampsia (PE) assumes that they develop as a result of
      placenta malfunctioning at the early stage of pregnancy. Placental dysfunction is
      also associated with the decreased activity of 11beta-hydroxysteroid
      dehydrogenase 2 (11beta-HSD2), which in normal pregnancy protects the fetus from
      the excess of maternal cortisol. OBJECTIVE: The aim of the study was to analyze
      the sequence of HSD11B2, a gene that encodes 11beta-HSD2, searching for mutations
      and haplotypes associated with the increased risk of GH or PE. Those may serve as
      potential genetic markers of GH and PE. METHODS: The study was performed in case
      control structure and included pregnant women (in third trimester) diagnosed
      with: GH, PE or being normotensive (control group). The research comprised DNA
      sequencing of HSD11B2, followed by restriction analysis (PCR-RFLP). The linkage
      disequilibrium analysis and haplotype-based case-control analysis were performed.
      RESULTS: Six sequence variations were observed. Four mutations were indicated in
      the coding region of HSD11B2 and the other two in 3'-UTR. Two SNPs: c.468C > A
      and c.534G > A were found to be in total disequilibrium. CONCLUSIONS: High
      variability in HSD11B2 sequence was indicated in the study population, but the
      relevance of observed SNPs to GH or PE development was not confirmed.

PMID- 27686601
TI  - "Who Does What?" Ensuring High-Quality and Coordinated Palliative Care With Our
      Oncology Colleagues.

PMID- 27686598
TI  - The regulation of iron metabolism by hepcidin contributes to unloading-induced
      bone loss.
AB  - Iron overload inhibits osteoblast function and promotes osteoclastogenesis.
      Hepcidin plays an important role in this process. The changes in iron content and
      the regulation of hepcidin under unloading-induced bone loss remain unknown. A
      hindlimb suspension model was adopted to simulate unloading-induced bone loss in
      mice. The results showed that iron deposition in both liver and bone was markedly
      increased in hindlimb unloaded mice, and was accompanied by the upregulation of
      osteoclast activity and downregulation of osteoblast activity. The iron chelator
      deferoxamine mesylate (DFO) reduced the iron content in bone and alleviated
      unloading-induced bone loss. The increased iron content in bone was mainly a
      result of the upregulation of transferrin receptor 1 (TfR1) and divalent metal
      transporter 1 with iron response element (DMT1+IRE), rather than changes in the
      iron transporter ferroportin 1 (FPN1). The hepcidin level in the liver was
      significantly higher, while the FPN1 level in the duodenum was substantially
      reduced. However, there were no changes in the FPN1 level in bone tissue. During
      hindlimb unloading, downregulation of hepcidin by siRNA increased iron uptake in
      bone and liver, which aggravated unloading-induced bone loss. In summary, these
      data show that unloading-induced bone loss was orchestrated by iron overload and
      coupled with the regulation of hepcidin by the liver.

PMID- 27686602
TI  - Association of recipient age and causes of heart transplant mortality:
      Implications for personalization of post-transplant management-An analysis of the
      International Society for Heart and Lung Transplantation Registry.
AB  - BACKGROUND: Survival beyond 1 year after heart transplantation has remained
      without significant improvement for the last 2 decades. A more individualized
      approach to post-transplant care could result in a reduction of long-term
      mortality. Although recipient age has been associated with an increased incidence
      of certain post-transplant morbidities, its effect on cause-specific mortality
      has not been established. METHODS: We analyzed overall and cause-specific
      mortality of heart transplant recipients registered in the International Society
      for Heart and Lung Transplantation Registry between 1995 and 2011. Patients were
      grouped by recipient age: 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and
      >= 70 years. Multivariable regression models were used to examine the association
      between recipient age and leading causes of post-transplant mortality. We also
      compared immunosuppression (IS) use among the different recipient age groups.
      RESULTS: There were 52,995 recipients (78% male; median age [5th, 95th
      percentile]: 54 [27, 66] years). Survival through 10 years after transplant was
      lower in heart transplant recipients in the 2 more advanced age groups: 49% for
      60 to 69 years and 36% for >= 70 years (p < 0.01 for pairwise comparisons with
      remaining groups). The risk of death caused by acute rejection (hazard ratio
      [HR], 4.11; p < 0.01), cardiac allograft vasculopathy (HR, 2.85; p < 0.01), and
      graft failure (HR, 2.29; p < 0.01) was highest in the youngest recipients (18-29
      years) compared with the reference group (50-59 years). However, the risk of
      death caused by infection (HR, 2.10; p < 0.01) and malignancy (HR, 2.23; p <
      0.01) was highest in older recipients (>= 70 years). Similarly, the risk of death
      caused by renal failure was lower in younger recipients than in the reference
      group (HR, 0.53; p < 0.01 for 18-49 years vs 50-59 years). The use of induction
      IS was similar among the different recipient age groups, and differences in
      maintenance IS were not clinically important. CONCLUSIONS: Causes of death in
      this large cohort of heart transplant recipients varied significantly with
      recipient age at the time of transplant, with cause-specific mortality profiles
      suggesting a possible effect of inadequate IS in younger recipients and over-IS
      in older recipients. Thus, a more personalized approach, possibly including
      different IS strategies according to recipient age, might result in improved post
      transplant survival.

PMID- 27686603
TI  - Facile ratiometric fluorapatite nanoprobes for rapid and sensitive bacterial
      spore biomarker detection.
AB  - Since bacterial spores, such as Bacillus anthracis spores, are extremely
      hazardous to human beings and animals, efforts have focused on the development of
      bacterial spore detector with rapid response and high selectivity and
      sensitivity. Therefore, we reported a facile one-step chelating-reagent-assisted
      hydrothermal synthesis of lanthanide-doped fluorapatite (FA) nanoprobes for
      detecting the biomarker of bacterial spores. In FA synthesis,
      ethylenediaminetetraacetic acid (EDTA) can serve not only as a shape controller
      and a stabilizer but also as a chelating reagent for lanthanide ions. After the
      fabrication, terbium (or europium) ions were not only embedded into lattice
      models of FA nanocrystals, but also chelated by EDTA on the surface of the FA
      nanocrystals, which can be available for detecting the biomarker (i.e.,
      dipicolinic acid) of bacterial spores. The obtained FA: Ln-EDTA nanoprobes can
      provide reference fluorescence which play crucial roles in the calibration and
      correction of concentration. The fluorescence intensities of FA: Tb-EDTA or FA:
      Eu-EDTA from Tb3+ or Eu3+ emission were highly sensitive and increased gradually
      with increasing DPA concentrations. The limit of detection of FA: Tb-EDTA was
      8.2nM, which is lower than that of FA: Eu-EDTA (20.9nM). It can be attributed to
      the fact that DPA can achieve a more effective energy transfer to Tb3+ than to
      Eu3+. Additionally, the nanoprobes were successfully applied for the
      determination of DPA in fetal calf serum samples. Given their rapid response and
      high sensitivity and selectivity, these ratiometric fluorescent nanoprobes are
      promising tools for the detection of bacterial spores.

PMID- 27686605
TI  - A unique iridium(III) complex-based chemosensor for multi-signal detection and
      multi-channel imaging of hypochlorous acid in liver injury.
AB  - Although hypochlorous acid (HOCl) has long been associated with a number of
      inflammatory diseases in mammalian bodies, the functions of HOCl in specific
      organs at abnormal conditions, such as liver injury, remain unclear due to its
      high reactivity and the lack of effective methods for its detection. Herein, a
      unique Ir(III) complex-based chemosensor, Ir-Fc, was developed for highly
      sensitive and selective detection of HOCl. Ir-Fc was designed by incorporating a
      ferrocene (Fc) quencher to a Ir(III) complex through a HOCl-responsive linker. In
      the presence of HOCl, the fast cleavage of Fc moiety in less than 1s led to the
      enhancement of photoluminescence (PL) and electrochemical luminescence (ECL), by
      which the concentration of HOCl was determined by both PL and ECL analysis.
      Taking advantages of excellent properties of Ir(III) complexes, optical and
      electrochemical analyses of the response of Ir-Fc towards HOCl were fully
      investigated. Followed by the measurements of low cytotoxicity of Ir-Fc by MTT
      analysis, one-photon (OP), two-photon (TP) and lifetime imaging experiments were
      conducted to visualise the generation of HOCl in live microphage and HepG2 cells,
      and in zebrafish and mouse, respectively. Furthermore, the generation and
      distribution of HOCl in liver cells and liver injury of zebrafish and mouse were
      investigated. The results demonstrated the applicability of Ir-Fc as an effective
      chemosensor for imaging of HOCl generation in mitochondria of cells and liver
      injury in vivo, implying the potential of Ir-Fc for biomedical diagnosis and
      monitoring applications.

PMID- 27686604
TI  - Nanostructured cobalt phosphates as excellent biomimetic enzymes to sensitively
      detect superoxide anions released from living cells.
AB  - Monitoring superoxide anion radicals in living cells has been attracting much
      academic and industrial interest due to the dual roles of the radicals. Herein,
      we synthesized a novel nanostructured cobalt phosphate nanorods (Co3(PO4)2 NRs)
      with tunable pore structure using a simple and effective micro-emulsion method
      and explored their potential utilization in the electrochemical sensing of
      superoxide anions. As an analytical and sensing platform, the nanoscale
      biomimetic enzymes Co3(PO4)2 NRs exhibited excellent selectivity and sensitivity
      towards superoxide anion (O2*-) with a low detection limit (2.25nM), wide linear
      range (5.76-5396nM), and long-term stability. Further, the nanoscale biomimetic
      enzyme could be efficiently applied in situ to electrochemically detect O2*-
      released from human malignant melanoma cells and normal keratinocyte, showing
      excellent real time quantitative detection capability. This material open up
      exciting opportunities for implementing biomimetic enzymes in nanoscale
      transition metal phosphates and designing enzyme-free biosensors with much higher
      sensitivity and durability in health and disease analysis than those of natural
      one.

PMID- 27686606
TI  - Direct determination of small RNAs using a biotinylated polythiophene
      impedimetric genosensor.
AB  - Herein, direct determination of small RNAs is described using a functional
      polymer modified genosensor. The analytical strategy adopted involves deposition
      by electropolymerization of biotinylated polythiophene films on the surface of
      miniaturized, disposable, gold screen-printed electrodes, followed by the layer
      by-layer deposition of streptavidin, and then biotynilated capture probes. A
      small RNA (miR-221) target was determined via the impedimetric measurement of the
      hybridization event in a label-free and PCR-free approach. Under optimized
      conditions, the limit of detection (LOD) was 0.7 pM miR-221 (15% RSD). The
      genosensor was applied for determination of miR-221 in total RNA extracted from
      human lung and breast cancer cell lines, discriminating between the cancer
      positive and -negative cells, without any amplification step, in less than 2h.

PMID- 27686607
TI  - Lipid content and fatty acid profile during lake whitefish embryonic development
      at different incubation temperatures.
AB  - Lipids serve as energy sources, structural components, and signaling molecules
      during fish embryonic development, and utilization of lipids may vary with
      temperature. Embryonic energy utilization under different temperatures is an
      important area of research in light of the changing global climate. Therefore, we
      examined percent lipid content and fatty acid profiles of lake whitefish
      (Coregonus clupeaformis) throughout embryonic development at three incubation
      temperatures. We sampled fertilized eggs and embryos at gastrulation, eyed and
      fin flutter stages following chronic incubation at temperatures of 1.8, 4.9 and
      8.0 degrees C. Hatchlings were also sampled following incubation at temperatures
      of 3.3, 4.9 and 8.0 degrees C. Fertilized eggs had an initial high percentage of
      dry mass composed of lipid (percent lipid content; ~29%) consisting of ~20%
      saturated fatty acids (SFA), ~32% monounsaturated fatty acids (MUFA), ~44%
      polyunsaturated fatty acids (PUFA), and 4% unidentified. The most abundant fatty
      acids were 16:0, 16:1, 18:1(n-9c), 20:4(n-6), 20:5(n-3) and 22:6(n-3). This lipid
      profile matches that of other cold-water fish species. Percent lipid content
      increased during embryonic development, suggesting protein or other yolk
      components were preferentially used for energy. Total percentage of MUFA
      decreased during development, which indicated MUFA were the primary lipid
      catabolized for energy during embryonic development. Total percentage of PUFA
      increased during development, driven largely by an increase in 22:6(n-3).
      Temperature did not influence percent lipid content or percent MUFA at any
      development stage, and had inconsistent effects on percent SFA and percent PUFA
      during development. Thus, lake whitefish embryos appear to be highly adapted to
      low temperatures, and do not alter lipids in response to temperature within their
      natural incubation conditions.

PMID- 27686608
TI  - Creation of an apoptin-derived peptide that interacts with SH3 domains and
      inhibits glioma cell migration and invasion.
AB  - Glioblastoma multiforme (GBM) is an aggressive tumor of the central nervous
      system characterized by high rates of recurrence, morbidity, and mortality. This
      study investigated the antitumor effects of an apoptin-derived peptide (ADP) on
      glioma cells and explored the underlying mechanisms. The U251, U87, and C6 glioma
      cell lines were used in the present study, and the expression of p-Akt, Akt, and
      MMP-9 was determined through Western blotting, quantitative real-time PCR, and
      hematoxylin and eosin (HE) staining. Tumor growth was evaluated by magnetic
      resonance imaging, and cell viability was assessed through an 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay. Glioma cell
      metastasis was evaluated using transwell migration, invasion, and scratch-wound
      assays. An ADP was designed and synthesized based on the results of a domain
      based analysis of the structure of apoptin. The ADP inhibited glioma cell
      viability, invasion and migration, and treatment with the synthesized ADP led to
      downregulation of p-Akt and MMP-9 and inhibited MMP-9 translation. The ADP also
      inhibited glioma invasion and migration in vivo, and HE staining showed decreases
      in the satellite-like invasion of cell masses and apoptotic cell populations
      after treatment with the ADP. Our findings demonstrate that treatment with an ADP
      can suppress glioma cell migration and invasion via the PI3K/Akt/MMP-9 signaling
      pathway and provide a new platform for the development of drugs for treating
      glioma.

PMID- 27686609
TI  - Colistin versus polymyxin B for the treatment of patients with multidrug
      resistant Gram-negative infections: a systematic review and meta-analysis.
AB  - Colistin and polymyxin B (PMB) have different pharmacokinetic profiles and minor
      differences in antimicrobial activities that may result in discrepancies in
      mortality and nephrotoxicity. A systematic review and meta-analysis was
      conducted. PubMed, Scopus and Cochrane Library databases were searched. There was
      no significant difference in unadjusted mortality between patients treated with
      colistin and PMB [risk ratio (RR) = 0.71, 95% confidence interval (CI) 0.45
      1.13]. Adjusted data were not available. Unadjusted nephrotoxicity was more
      common in patients treated with colistin than PMB (RR = 1.55, 95% CI 1.36-1.78).
      According to the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End
      stage kidney disease) criteria, there was no difference regarding risk, injury or
      failure between colistin and PMB. Although episodes of loss of renal function
      were few in general, they developed primarily in colistin-treated patients (RR =
      8.55, 95% CI 1.48-49.49). Colistin was associated with more episodes of
      nephrotoxicity that also occurred sooner in the analysis of adjusted data (hazard
      ratio = 2.16, 95% CI 1.43-3.27). Colistin administration was an independent risk
      factor for nephrotoxicity in two studies. Future studies should evaluate in depth
      the factors associated with mortality and nephrotoxicity in patients treated with
      polymyxins and the impact of polymyxin-associated nephrotoxicity on mortality.

PMID- 27686610
TI  - Management of infection by the Zika virus.
AB  - A panel of national experts was convened by the Brazilian Infectious Diseases
      Society in order to organize the national recommendations for the management of
      zika virus infection. The focus of this document is the diagnosis, both clinical
      and laboratorial, and appropriate treatment of the diverse manifestations of this
      infection, ranging from acute mild disease to Guillain-Barre syndrome and also
      microcephaly and congenital malformations.

PMID- 27686611
TI  - Searching and synthesising 'grey literature' and 'grey information' in public
      health: critical reflections on three case studies.
AB  - BACKGROUND: Grey literature includes a range of documents not controlled by
      commercial publishing organisations. This means that grey literature can be
      difficult to search and retrieve for evidence synthesis. Much knowledge and
      evidence in public health, and other fields, accumulates from innovation in
      practice. This knowledge may not even be of sufficient formality to meet the
      definition of grey literature. We term this knowledge 'grey information'. Grey
      information may be even harder to search for and retrieve than grey literature.
      METHODS: On three previous occasions, we have attempted to systematically search
      for and synthesise public health grey literature and information-both to
      summarise the extent and nature of particular classes of interventions and to
      synthesise results of evaluations. Here, we briefly describe these three 'case
      studies' but focus on our post hoc critical reflections on searching for and
      synthesising grey literature and information garnered from our experiences of
      these case studies. We believe these reflections will be useful to future
      researchers working in this area. RESULTS: Issues discussed include search
      methods, searching efficiency, replicability of searches, data management, data
      extraction, assessing study 'quality', data synthesis, time and resources, and
      differentiating evidence synthesis from primary research. CONCLUSIONS:
      Information on applied public health research questions relating to the nature
      and range of public health interventions, as well as many evaluations of these
      interventions, may be predominantly, or only, held in grey literature and grey
      information. Evidence syntheses on these topics need, therefore, to embrace grey
      literature and information. Many typical systematic review methods for searching,
      appraising, managing, and synthesising the evidence base can be adapted for use
      with grey literature and information. Evidence synthesisers should carefully
      consider the opportunities and problems offered by including grey literature and
      information. Enhanced incentives for accurate recording and further
      methodological developments in retrieval will facilitate future syntheses of grey
      literature and information.

PMID- 27686612
TI  - Plasma CTGF is independently related to an increased risk of cardiovascular
      events and mortality in patients with atherosclerotic disease: the SMART study.
AB  - AIMS: Connective tissue growth factor (CTGF) plays a key role in tissue
      fibrogenesis and growing evidence indicates a pathogenic role in cardiovascular
      disease. Aim of this study is to investigate the association of connective tissue
      growth factor (CTGF/CCN2) with cardiovascular risk and mortality in patients with
      manifest vascular disease. METHODS AND RESULTS: Plasma CTGF was measured by ELISA
      in a prospective cohort study of 1227 patients with manifest vascular disease
      (mean age 59.0 +/- 9.9 years). Linear regression analysis was performed to
      quantify the association between CTGF and cardiovascular risk factors. Results
      are expressed as beta (beta) regression coefficients with 95% confidence
      intervals (CI). The relation between CTGF and the occurrence of new
      cardiovascular events and mortality was assessed with Cox proportional hazard
      analysis. Adjustments were made for potential confounding factors. Plasma CTGF
      was positively related to total cholesterol (beta 0.040;95%CI 0.013-0.067) and
      LDL cholesterol (beta 0.031;95%CI 0.000-0.062) and inversely to glomerular
      filtration rate (beta -0.004;95%CI -0.005 to -0.002). CTGF was significantly
      lower in patients with cerebrovascular disease. During a median follow-up of 6.5
      years (IQR 5.3-7.4) 131 subjects died, 92 experienced an ischemic cardiac
      complication and 45 an ischemic stroke. CTGF was associated with an increased
      risk of new vascular events (HR 1.21;95%CI 1.04-1.42), ischemic cardiac events
      (HR 1.41;95%CI 1.18-1.67) and all-cause mortality (HR 1.18;95%CI 1.00-1.38) for
      every 1 nmol/L increase in CTGF. No relation was observed between CTGF and the
      occurrence of ischemic stroke. CONCLUSIONS: In patients with manifest vascular
      disease, elevated plasma CTGF confers an increased risk of new cardiovascular
      events and all-cause mortality.

PMID- 27686614
TI  - Somatostatin regulates NHE8 protein expression via the ERK1/2 MAPK pathway in DSS
      induced colitis mice.
AB  - Previous studies reported that administration of somatostatin (SST) to human
      patients mitigated their diarrheal symptoms. Octreotide (an analog of SST)
      treatment in animals resulted in upregulation of sodium/hydrogen exchanger 8
      (NHE8). NHE8 is important for water/sodium absorption in the intestine, and loss
      of NHE8 function results in mucosal injury. Thus we hypothesized that NHE8
      expression is inhibited during colitis and that SST treatment during pathological
      conditions can restore NHE8 expression. Our data showed for the first time that
      NHE8 is expressed in the human colonic tissue and that NHE8 expression is
      decreased in ulcerative colitis (UC) patients. We also found that octreotide
      could stimulate colonic NHE8 expression in colitic mice. Furthermore, the
      somatostatin receptor 2 (SSTR2) agonist seglitide and the somatostatin receptor 5
      (SSTR5) agonist L-817,818 could restore NHE8 expression via its role in
      suppressing ERK1/2 phosphorylation. Our study uncovered a novel mechanism of SST
      stimulation of NHE8 expression in colitis.

PMID- 27686613
TI  - Comprehensive analysis of microRNA signature of mouse pancreatic acini:
      overexpression of miR-21-3p in acute pancreatitis.
AB  - In the current study, we have characterized the global miRNA expression profile
      in mouse pancreatic acinar cells and during acute pancreatitis using next
      generation RNA sequencing. We identified 324 known and six novel miRNAs that are
      expressed in mouse pancreatic acinar cells. In the basal state, miR-148a-3p, miR
      375-3p, miR-217-5p, and miR-200a-3p were among the most abundantly expressed,
      whereas miR-24-5p and miR-421-3p were the least abundant. Treatment of acinar
      cells with caerulein (100 nM) and taurolithocholic acid 3-sulfate [TLC-S (250
      MUM)] induced numerous changes in miRNA expression profile. In particular, we
      found significant overexpression of miR-21-3p in acini treated with caerulein and
      TLC-S. We further looked at the expression of miR-21-3p in caerulein, l-arginine,
      and caerulein + LPS-induced acute pancreatitis mouse models and found 12-, 21-,
      and 50-fold increased expression in the pancreas, respectively. In summary, this
      is the first comprehensive analysis of global miRNA expression profile of mouse
      pancreatic acinar cells in normal and disease conditions. Our analysis shows that
      miR-21-3p expression level correlates with the severity of the disease.

PMID- 27686616
TI  - Optimizing ankle performance when taped: Effects of kinesiology and athletic
      taping on proprioception in full weight-bearing stance.
AB  - OBJECTIVES: To explore the effects of kinesiology taping (KT) and athletic taping
      (AT) on ankle proprioception when tested in functional, full weight-bearing
      stance. DESIGN: Cross-sectional study. METHODS: Twenty-four healthy university
      students participated. Proprioception was measured using the Active Movement
      Extent Discrimination Apparatus (AMEDA). The three testing conditions: no-taping,
      KT, AT, and foot tested were randomly assigned. Perceived comfort, support and
      proprioceptive performance under two taping conditions were recorded. RESULTS:
      Proprioceptive discrimination scores with 95% CIs for no-taping, KT and AT were
      0.81 (0.79-0.84), 0.81 (0.79-0.83), and 0.79 (0.77-0.81). Repeated measures ANOVA
      showed neither any significant difference associated with taping compared with no
      taping (p=0.30), nor any difference between KT and AT (p=0.19). The group was
      then divided, according to their no-taping scores, into two sub-groups: with
      scores below the no-taping mean (n=13), and above the mean (n=11). ANOVA revealed
      a significant interaction (p=0.008) indicating that above-average no-taping
      performers proprioception scores were worse when taped, whereas below-average
      performers improved. For both KT and AT, only ratings of perceived comfort when
      taped were significantly associated with actual proprioceptive performance (both
      r>0.44, p<=0.03). Other perception ratings (support and performance) were
      significantly inter-correlated (both r>0.42, p<0.04), but neither was
      significantly correlated with actual performance (both p>0.31). CONCLUSIONS:
      Taping of the foot and ankle may amplify sensory input in a way that enhances
      proprioception of poor performers but produces an input overload that impairs
      proprioception in those who originally performed well when no-taping. Screening
      of ankle proprioception may identify those who would benefit most from taping.

PMID- 27686617
TI  - Synthesis of magMCM-41 with rice husk silica as cadmium sorbent from aqueous
      solutions: parameters' optimization by response surface methodology.
AB  - The magnetic mesoporous silica of magMCM-41 with large surface area (695 m2 g-1)
      and high magnetization (10.79 emu g-1) was synthesized using extracted amorphous
      silica from rice husk. The synthesized materials were applied for adsorption of
      Cd(II) ions from aqueous solution in batch operation systems. A highly selective
      adsorbent was obtained by grafting 3-aminopropyltrimethoxysilane on the pores of
      the magMCM-41 in which the adsorption capacity of Cd(II) ions increased from 41.8
      to 86 mg g-1, under the same conditions. A total of 20 sets of experiments were
      planned by the central composite design under response surface methodology. The
      effects of three independent variables pH, initial Cd(II) ion concentration and
      sorbent dosage were investigated on the adsorption capacity (qe) and removal
      efficiency (R) of cadmium. The best responses for Cd(II) adsorption capacity and
      removal efficiency were 493.21 mg g-1 and 60.25%, respectively, which was
      achieved at pH of 5.05, sorbent dosage of 0.1 g L-1 and Cd(II) concentration of
      150 mg L-1. Additionally, the obtained value for desirability was equal to 0.807.
      The theoretical isotherm models were applied to describe the adsorption process
      that the Langmuir model provides the best correlation of the equilibrium data.
      The kinetics study revealed that data from the experiments fitted well to the
      pseudo-second-order equation than the pseudo-first-order equation. The
      thermodynamic parameters revealed that the adsorption process strongly depended
      on temperature and indicated the exothermic behavior and spontaneous nature of
      the adsorption.

PMID- 27686618
TI  - Adversity and Justice.

PMID- 27686619
TI  - Corrigendum.

PMID- 27686620
TI  - Neurolymphomatosis as a relapse of primary cerebral nervous system lymphoma.

PMID- 27686615
TI  - Precision medicine in alcoholic and nonalcoholic fatty liver disease via
      modulating the gut microbiota.
AB  - Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)
      represent a major health burden in industrialized countries. Although alcohol
      abuse and nutrition play a central role in disease pathogenesis, preclinical
      models support a contribution of the gut microbiota to ALD and NAFLD. This review
      describes changes in the intestinal microbiota compositions related to ALD and
      NAFLD. Findings from in vitro, animal, and human studies are used to explain how
      intestinal pathology contributes to disease progression. This review summarizes
      the effects of untargeted microbiome modifications using antibiotics and
      probiotics on liver disease in animals and humans. While both affect humoral
      inflammation, regression of advanced liver disease or mortality has not been
      demonstrated. This review further describes products secreted by Lactobacillus-
      and microbiota-derived metabolites, such as fatty acids and antioxidants, that
      could be used for precision medicine in the treatment of liver disease. A better
      understanding of host-microbial interactions is allowing discovery of novel
      therapeutic targets in the gut microbiota, enabling new treatment options that
      restore the intestinal ecosystem precisely and influence liver disease. The
      modulation options of the gut microbiota and precision medicine employing the gut
      microbiota presented in this review have excellent prospects to improve treatment
      of liver disease.

PMID- 27686621
TI  - MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a
      novel tumor suppressor by regulating HMGA2.
AB  - This study aimed to understand the exact function and potential mechanism of miR
      4500 in colorectal cancer (CRC). In this study, the expression of miR-4500 was
      decreased in both CRC cells and tissues, and downregulated miR-4500 indicated
      advanced tumor stage and poor survival. By bisulfite sequencing analysis, we
      found that the CpG island in the promoter region of miR-4500 was hypermethylated
      in CRC cells and tissues compared with normal control cells and non-tumor
      tissues, respectively. Functionally, gain- and loss-of-function analyses
      indicated the tumor suppressor role of miR-4500: it suppressed cell
      proliferation, cell cycle progression, migration, and invasion. Predictive
      algorithms and experimental analyses identified HMGA2 as a direct target of miR
      4500. Reintroducing HMGA2 impaired the inhibitory effects of miR-4500 on cell
      growth and motility. Clinically, higher HMGA2 protein expression in CRC tissues
      was associated with advanced tumor stage and poor survival. An inverse
      correlation was found between miR-4500 levels and HMGA2 protein expression. Taken
      together, this study provides the first evidence that miR-4500 functions as a
      novel tumor suppressor in the miR-4500/HMGA2 axis in colorectal carcinogenesis,
      and restoring miR-4500 expression might represent a promising therapeutic
      strategy for CRC.

PMID- 27686622
TI  - Adhesive ligand tether length affects the size and length of focal adhesions and
      influences cell spreading and attachment.
AB  - Cells are known to respond to physical cues from their microenvironment such as
      matrix rigidity. Discrete adhesive ligands within flexible strands of fibronectin
      connect cell surface integrins to the broader extracellular matrix and are
      thought to mediate mechanosensing through the cytoskeleton-integrin-ECM linkage.
      We set out to determine if adhesive ligand tether length is another physical cue
      that cells can sense. Substrates were covalently modified with adhesive
      arginylglycylaspartic acid (RGD) ligands coupled with short (9.5 nm), medium
      (38.2 nm) and long (318 nm) length inert polyethylene glycol tethers. The size
      and length of focal adhesions of human foreskin fibroblasts gradually decreased
      from short to long tethers. Furthermore, we found cell adhesion varies in a
      linker length dependent manner with a remarkable 75% reduction in the density of
      cells on the surface and a 50% reduction in cell area between the shortest and
      longest linkers. We also report the interplay between RGD ligand concentration
      and tether length in determining cellular spread area. Our findings show that
      without varying substrate rigidity or ligand density, tether length alone can
      modulate cellular behaviour.

PMID- 27686623
TI  - Non-specific alarm calls trigger mobbing behavior in Hainan gibbons (Nomascus
      hainanus).
AB  - Alarm calls are important defensive behaviors. Here, we report the acoustic
      spectrum characteristics of alarm calls produced by Hainan gibbons (Nomascus
      hainanus) inhabiting Bawangling National Nature Reserve in Hainan, China.
      Analysis of call data collected from 2002-2014 shows that alarm calls are emitted
      by all family group members, except infants. Alarm behavior included simple short
      alarming calls (7-10 min) followed by longer variable-frequency mobbing calls
      lasting 5-12 min. The duration of individual alarming and mobbing calls was 0.078
      +/- 0.014 s and 0.154 +/- 0.041 s at frequency ranges of 520-1000 Hz and 690-3920
      Hz, respectively. Alarming call duration was positively associated with group
      size. The alarm calls can trigger mobbing behavior in Hainan gibbons; this is a
      defense way of social animals, and first report among the primates' species. The
      system of vocal alarm behavior described in this critically endangered species is
      simple and effective.

PMID- 27686624
TI  - SCOP/PHLPP1beta mediates circadian regulation of long-term recognition memory.
AB  - Learning and memory depend on the time of day in various organisms, but it is not
      clear whether and how the circadian clock regulates memory performance. Here we
      show that consolidation of long-term recognition memory is a circadian-regulated
      process, which is blunted by disruption of the hippocampal clock. We focused on
      SCOP, a key molecule regulating hippocampus-dependent long-term memory for
      objects. The amounts of SCOP and its binding partner K-Ras in the hippocampal
      membrane rafts exhibit robust circadian changes, and SCOP knockdown in the
      hippocampal CA1 impairs long-term memory at night. Circadian changes in stimulus
      dependent activation of ERK in the hippocampal neurons are dependent on the SCOP
      levels in the membrane rafts, while Scop knockout abrogates the activation
      rhythm. We conclude that long-term memory formation is regulated by the circadian
      clock through SCOP dynamics in the membrane rafts of the hippocampal CA1.

PMID- 27686625
TI  - Exosomes derived from MSCs ameliorate retinal laser injury partially by
      inhibition of MCP-1.
AB  - Although accumulated evidence supports the notion that mesenchymal stem cells
      (MSCs) act in a paracrine manner, the mechanisms are still not fully understood.
      Recently, MSC-derived exosomes (MSC-Exos), a type of microvesicle released from
      MSCs, were thought to carry functional proteins and RNAs to recipient cells and
      play therapeutic roles. In the present study, we intravitreally injected MSCs
      derived from either mouse adipose tissue or human umbilical cord, and their
      exosomes to observe and compare their functions in a mouse model of laser-induced
      retinal injury. We found that both MSCs and their exosomes reduced damage,
      inhibited apoptosis, and suppressed inflammatory responses to obtain better
      visual function to nearly the same extent in vivo. Obvious down-regulation of
      monocyte chemotactic protein (MCP)-1 in the retina was found after MSC-Exos
      injection. In vitro, MSC-Exos also down-regulated MCP-1 mRNA expression in
      primarily cultured retinal cells after thermal injury. It was further
      demonstrated that intravitreal injection of an MCP-1-neutralizing antibody
      promoted the recovery of retinal laser injury, whereas the therapeutic effect of
      exosomes was abolished when MSC-Exos and MCP-1 were administrated simultaneously.
      Collectively, these results suggest that MSC-Exos ameliorate laser-induced
      retinal injury partially through down-regulation of MCP-1.

PMID- 27686627
TI  - Usefulness of direct fluorescent in buffy coat in the diagnosis of Candida sepsis
      in neonates.

PMID- 27686626
TI  - PLGA nanoparticle encapsulation reduces toxicity while retaining the therapeutic
      efficacy of EtNBS-PDT in vitro.
AB  - Photodynamic therapy regimens, which use light-activated molecules known as
      photosensitizers, are highly selective against many malignancies and can bypass
      certain challenging therapeutic resistance mechanisms. Photosensitizers such as
      the small cationic molecule EtNBS (5-ethylamino-9-diethyl
      aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells
      that reside within acidic and hypoxic tumour microenvironments. At higher doses,
      however, these photosensitizers induce "dark toxicity" through light-independent
      mechanisms. In this study, we evaluated the use of nanoparticle encapsulation to
      overcome this limitation. Interestingly, encapsulation of the compound within
      poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-EtNBS) was found to
      significantly reduce EtNBS dark toxicity while completely retaining the
      molecule's cytotoxicity in both normoxic and hypoxic conditions. This dual effect
      can be attributed to the mechanism of release: EtNBS remains encapsulated until
      external light irradiation, which stimulates an oxygen-independent, radical
      mediated process that degrades the PLGA nanoparticles and releases the molecule.
      As these PLGA-encapsulated EtNBS nanoparticles are capable of penetrating deeply
      into the hypoxic and acidic cores of 3D spheroid cultures, they may enable the
      safe and efficacious treatment of otherwise unresponsive tumour regions.

PMID- 27686628
TI  - Synthesis of maltodextrin-grafted-cinnamic acid and evaluation on its ability to
      stabilize anthocyanins via microencapsulation.
AB  - In this work, maltodextrin-grafted-cinnamic acid (MD-g-CA) was synthesised and
      used as wall material to improve the stability of purple sweet potato
      anthocyanins (PSPa) via microencapsualtion. MD-g-CA was prepared through
      esterification in a two-step convenient synthesis procedure and characterised
      using infra-red (IR) spectroscopy. The IR data indicated the typical ester
      carbonyl stretching at around 1721 cm-1. Moreover, MD-g-CA could give about 40%
      inhibition of DPPH radical and present excellent UV-absorption, which were
      notably better than that of native MD. Maltodextrin (MD) and MD-g-CA were used to
      prepare PSPa microcapsules by spray drying. The stability of PSPa was evaluated
      by UV-Vis analysis. The microcapsules produced by MD-g-CA showed a spheres-like
      appearance with some cracks. Storage tests revealed that the degradation rate of
      PSPa embedded by MD-g-CA was much lower than that of free PSPa under the same
      condition. Thus, MD-g-CA could be used as an effective wall material to improve
      stability of anthocyanins.

PMID- 27686629
TI  - A High-Throughput, Arbitrary-Waveform, MPI Spectrometer and Relaxometer for
      Comprehensive Magnetic Particle Optimization and Characterization.
AB  - Magnetic Particle Imaging (MPI) is a promising new tracer modality with zero
      attenuation deep in tissue, high contrast and sensitivity, and an excellent
      safety profile. However, the spatial resolution of MPI is limited to around 1 mm
      currently and urgently needs to be improved for clinical applications such as
      angiography and brain perfusion. Although MPI resolution is highly dependent on
      tracer characteristics and the drive waveforms, optimization is limited to a
      small subset of possible excitation strategies by current MPI hardware that only
      does sinusoidal drive waveforms at very few frequencies. To enable a more
      comprehensive and rapid optimization of drive waveforms for multiple metrics like
      resolution and signal strength simultaneously, we demonstrate the first untuned
      MPI spectrometer/relaxometer with unprecedented 400 kHz excitation bandwidth and
      capable of high-throughput acquisition of harmonic spectra (100 different drive
      field frequencies in only 500 ms). It is also capable of arbitrary drive-field
      waveforms which have not been experimentally evaluated in MPI to date. Its high
      throughput capability, frequency-agility and tabletop size makes this Arbitrary
      Waveform Relaxometer/Spectrometer (AWR) a convenient yet powerfully flexible tool
      for nanoparticle experts seeking to characterize magnetic particles and optimize
      MPI drive waveforms for in vitro biosensing and in vivo imaging with MPI.

PMID- 27686630
TI  - Psychometric Testing of the Self-Care of Coronary Heart Disease Inventory (SC
      CHDI).
AB  - Although coronary heart disease (CHD) requires a significant amount of self-care,
      there are no instruments available to measure self-care in this population. The
      purpose of this study was to test the psychometric properties of the Self-Care of
      Coronary Heart Disease Inventory (SC-CHDI). Using the Self-Care of Chronic
      Illness theory, we developed a 22-item measure of maintenance, management, and
      confidence appropriate for persons with stable CHD and tested it in a convenience
      sample of 392 adults (62% male, mean age 61.4 +/- 9.6 years). Factorial validity
      was tested with confirmatory factor analysis. Convergent validity was tested with
      the Medical Outcomes Study MOS-SAS Specific Adherence Scale and the Decision
      Making Competency Inventory (DMCI). Cronbach alpha and factor determinacy scores
      (FDS) were calculated to assess reliability. Two multidimensional self-care
      scales were confirmed: self-care maintenance included "consultative behaviors"
      (e.g., taking medicines as prescribed) and "autonomous behaviors" (e.g.,
      exercising 30 minute/day; FDS = .87). The multidimensional self-care management
      scale included "early recognition and response" (e.g., recognizing symptoms) and
      "delayed response" (e.g., taking an aspirin; FDS = .76). A unidimensional
      confidence factor captured confidence in each self-care process (alpha = .84).
      All the self-care dimensions were associated with treatment adherence as measured
      by the MOS-SAS. Only self-care maintenance and confidence were associated with
      decision-making (DCMI). These findings support the conceptual basis of self-care
      in patients with CHD as a process of maintenance that includes both consultative
      and autonomous behaviors, and management with symptom awareness and response. The
      SC-CHDI confidence scale is promising as a measure of self-efficacy, an important
      factor influencing self-care. (c) 2016 Wiley Periodicals, Inc.

PMID- 27686632
TI  - Evidence of Trivalent Am Substitution into U3O8.
AB  - U3O8 is considered to be the most stable phase for uranium oxide. Its structural
      properties must be accurately understood to foresee and manage aspects such as
      its leaching behavior when spent nuclear fuel is stored in an oxidative
      environment. Moreover, as fuel irradiation causes the formation of fission
      products and activation products such as plutonium and minor actinides, it is
      probable that U3O8 will be mixed with other chemical elements under real
      conditions of oxidation. The storage issue can be extended to americium
      transmutation, where the irradiated compounds are mixed oxides composed of
      uranium and americium. This study thus focused on determining the structural
      properties of a solid solution containing uranium and trivalent americium (U/Am
      ratio = 90/10) and synthesized so as to obtain conventional U3O8 oxide. This
      paper presents the possibility of combining trivalent americium with uranium in a
      U3O8 mixed oxide for the first time, despite the high valence and atomic ratio
      differences, and proposes novel structural arrangements. X-ray diffraction
      measurements reveal americium substitution in U3O8 uranium cationic sites,
      leading to phase transformation into a U3O8 high-temperature structure and
      general lattice swelling. X-ray absorption near-edge spectroscopy and extended X
      ray absorption fine structure experiments highlight an excess of U+VI organized
      in uranyl units as the main consequence of accommodation.

PMID- 27686631
TI  - DNA polymerase beta decrement triggers death of olfactory bulb cells and impairs
      olfaction in a mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) involves the progressive degeneration of neurons
      critical for learning and memory. In addition, patients with AD typically exhibit
      impaired olfaction associated with neuronal degeneration in the olfactory bulb
      (OB). Because DNA base excision repair (BER) is reduced in brain cells during
      normal aging and AD, we determined whether inefficient BER due to reduced DNA
      polymerase-beta (Polbeta) levels renders OB neurons vulnerable to degeneration in
      the 3xTgAD mouse model of AD. We interrogated OB histopathology and olfactory
      function in wild-type and 3xTgAD mice with normal or reduced Polbeta levels.
      Compared to wild-type control mice, Polbeta heterozygous (Polbeta+/- ), and
      3xTgAD mice, 3xTgAD/Polbeta+/- mice exhibited impaired performance in a buried
      food test of olfaction. Polbeta deficiency did not affect the proliferation of OB
      neural progenitor cells in the subventricular zone. However, numbers of newly
      generated neurons were reduced by approximately 25% in Polbeta+/- and 3xTgAD
      mice, and by over 60% in the 3xTgAD/Polbeta+/- mice compared to wild-type control
      mice. Analyses of DNA damage and apoptosis revealed significantly greater
      degeneration of OB neurons in 3xTgAD/Polbeta+/- mice compared to 3xTgAD mice.
      Levels of amyloid beta-peptide (Abeta) accumulation in the OB were similar in
      3xTgAD and 3xTgAD/Polbeta+/- mice, and cultured Polbeta-deficient neurons
      exhibited increased vulnerability to Abeta-induced death. Olfactory deficit is an
      early sign in human AD, but the mechanism is not yet understood. Our findings in
      a new AD mouse model demonstrate that diminution of BER can endanger OB neurons,
      and suggest a mechanism underlying early olfactory impairment in AD.

PMID- 27686634
TI  - [Strategies for diagnosis and treatment of bladder cancer in precise times].
AB  - Bladder cancer is one of the most common malignant tumors of the urinary system
      in China, but it is still difficult to be accurate in the diagnosis and
      treatment. The rapid development of high-throughput sequencing technology and
      data analysis of biological information pushes the medicine to enter into the
      precise times. In the review, the recent progress of molecular subtype,
      assessment of immune and metastatic status, efficacy prediction of chemotherapy,
      immunotherapy and targeted therapy are summarized. It provides new ideas and
      methods for accurate diagnosis and treatment of bladder cancer.

PMID- 27686633
TI  - Management of swallowing in thrombolysed stroke patients: Implementation of a new
      protocol.
AB  - PURPOSE: There is a paucity of evidence regarding dysphagia management post
      thrombolysis. The aim of this case-control study was to evaluate the impact of a
      dysphagia management protocol on patient outcomes. Thrombolysis has been
      completed at our metropolitan hospital since 2011 and a dysphagia management
      protocol was developed in 2012. METHOD: Chart auditing was completed for 83
      participants in three groups: pre-protocol (n = 12) (2011), post-protocol (n =
      28) (2012-2014), and non-thrombolysed stroke patients (n = 43). RESULT: Following
      the implementation of this clinical protocol, the average time patient remained
      nil by mouth reduced by 9.5 h, the percentage of patients who were malnourished
      or at risk reduced by 24% and the number of patients who developed aspiration
      pneumonia reduced by 11%. The cost of hospital stay reduced by $1505. Service
      compliance with best practice in dysphagia management in thrombolysed patients
      increased from 67% to 96% in the thrombolysed patient groups. CONCLUSION: The
      outcomes suggest that a clinical protocol for dysphagia management in
      thrombolysed patients has the potential to improve service outcomes, reduce
      complications from dysphagia, have financial benefits for the hospital and
      increase service compliance. Furthermore, the results lend support for speech
      pathology services to manage dysphagia on weekends.

PMID- 27686635
TI  - [Key issues of nephron spring surgery for renal neoplasms].
AB  - In recent years the incidence of small renal carcinoma is increasing, and nephron
      sparing surgery(NSS) becomes the mainstream to treat it. NSS is considered based
      on comprehensive analysis: the imaging examination, systemic evaluation of the
      patients, and the indications of NSS. There are three common surgical approaches:
      intraperitoneal approach, retroperitoneal approach and the joint approach. It is
      recommended to do intraoperative frozen pathology. If the edge is positive, it is
      better to cut a deeper layer of the tissue around the renal tumor or transform to
      radical nephrectomy. Attention should also be paid to reduce heat ischemia time,
      in order to protect renal function and reduce postoperative renal atrophy. In
      addition, there are some factors, such as the accurate preoperative evaluation of
      renal function and surgical skill of the doctors, which can reduce the incidence
      of postoperative complications and improve survival and quality of life.

PMID- 27686636
TI  - [Effect of Sunitinib therapy on immune function of patients with advanced renal
      cell carcinoma].
AB  - Objective: To evaluate the effect of Sunitinib therapy on immune function of
      patient with advanced renal cell carcinoma. Methods: A total of 27 patient with
      advanced renal cell carcinoma who received Sunitinib therapy in Chongqing Cancer
      Hospital from July 2010 to July 2014 were recruited in a prospective cohort
      study.Nineteen were male patients and 8 were female patients aged from 36 to 75
      years with mean age of (58+/-7)years.Twenty-five cases were renal clear cell
      carcinoma, the other two cases were papillary renal cell carcinoma and Xp11.2
      translocation renal cell carcinoma.According to MSKCC terminal prognosis scoring
      recommend by NCCN: 22 cases were in low risk, 5 cases were in high risk.All the
      patient took Sunitinib 50 mg orally once daily for 4 weeks, followed-up by 2
      weeks.Flow cytometry was used to detect the levels of CD3+ , CD8+ , CD4+ T
      lymphocyte, NK cell and B lymphocyte in peripheral blood of patients before
      taking medicine.The levels of CD3+ , CD8+ , CD4+ T lymphocyte, NK cell, B
      lymphocyte in peripheral blood were detected again after 4 weeks, 6 weeks, 10
      weeks and the disease progression.Paired t-test was used to analyze the data
      comparison of two groups, mean comparison in groups was conducted with repeated
      measurements analysis of variance, and the pairwise comparison was performed with
      LSD-t method. Results: The levels of CD3+ , CD8+ T lymphocyte, NK cell, B
      lymphocyte were significantly increased after the therapy of Sunitinib for 1
      cycle(I-J was 212+/-22, 163+/-18, 59+/-12, 13.8+/-1.4, respectively, all P<0.05).
      The levels of CD3+ , CD8+ T lymphocyte, NK cell, B lymphocyte were significantly
      increased after the therapy of Sunitinib for 2 cycles(I-J was 362+/-43, 299+/-28,
      91+/-19, 28.1+/-3.9, respectively, all P<0.05), while the level of CD4+
      lymphocyte was decreased, but no significant difference(F=0.873, P>0.05). CD4+
      /CD8+ was significantly decreased after the therapy of Sunitinib for 1 cycle, and
      it went on decreasing after the therapy of Sunitinib for 2 cycles(I-J was -0.31+/
      0.03, -0.44+/-0.04, respectively, all P<0.05). Disease progression occurred in 10
      cases during the follow-up period.The NK cell, CD3+ , CD4+ , CD8+ T lymphocyte
      were significantly decreased when the disease progressed(t=2.39-5.769, all
      P<0.05). Conclusions: Sunitinib has effect on the immune function of patients
      with advanced renal cell carcinoma, and the progression of renal cell carcinoma
      is related to the immune function.It suggests that targeted drug therapy should
      be combined with biological immunotherapy, which may be the research direction
      for the treatment of advanced renal cell carcinoma.

PMID- 27686637
TI  - [Safety and efficacy of partial nephrectomy for solitary kidney tumor].
AB  - Objective: To explore the safety and clinical efficacy of partial nephrectomy for
      solitary kidney tumor. Methods: Twenty patients with a functional or anatomic
      solitary kidney who underwent nephron-sparing surgery for one or more renal
      masses were retrospectively analyzed. There were 15 male and 5 female patients
      with mean age of 63 years.Patients were divided into open partial
      nephrectomy(OPN) group and laparoscopic partial nephrectomy(LPN) group, the two
      groups were followed up.Demographic and clinical characteristics were analyzed
      using student t-test for continuous variables, and the chi2 test for categorical
      variables. Results: There were 21 tumors whose maximum diameter were 1.5 to 6.0
      cm, the mean size was (3.7+/-1.3)cm, mean operative time was (205.3+/
      81.8)minutes, and median estimated blood loss was 385.6 ml.Five cases accepted
      blood transfusion intro-operation, 1 case appeared leakage of urine post
      operation, none had obvious fever.Eighteen cases were clear cell carcinoma, 2
      cases were chromophobe renal carcinoma, 1 case was papillary renal cell
      carcinoma.Seventeen cases were T1aNxM0, 3 cases were T1bNxM0, 1 case was
      T3NxM0.One case lost to follow up, the others had completed a mean follow-up of
      21.5 months (ranging from 1 to 53 months). One case recurred, no one had
      metastasis, all patients were alive.The hemoglobin ((114.9+/-19.6)g/L) and
      estimated glomerular filtration rate(eGFR) ((46.5+/-18.2) ml/min) of
      postoperative day were lesser than pre-operation ((130.7+/-18.8)g/L, (58.0+/
      16.4) ml/min), while the serum creatinine was higher ((123.8+/-39.8) MUmol/L
      vs.(90.9+/-33.2) MUmol/L). Three months after operation, hemoglobin, serum
      creatinine and eGFR had no difference with pre-operative.Compared with OPN group,
      LPN group gain less blood loss (306 ml vs.510 ml)(t=-2.38, P=0.03), had shorter
      length of stays (15 d vs.21 d)(t=-3.34, P=0.04), had longer time of renal artery
      clamping (25.8 min vs.16.5 min)(t=2.60, P=0.02). Conclusions: Partial nephrectomy
      is secure and effective selection for solitary kidney tumor.The LPN has less
      trauma, gain less blood loss, recover faster and has shorter length of stays than
      the OPN, which needs shorter ischaemic time.

PMID- 27686638
TI  - [Transvesical single-site laparoscopic radical prostatectomy of 39 cases:
      technique and clinical outcomes].
AB  - Objectives: To present the surgical technique of transvesical single-site
      laparoscopic radical prostatectomy (TVSSLRP) and to evaluate its clinical
      efficacy. Methods: The clinical parameters of 39 patients who underwent
      transvesical single-site laparoscopic radical prostatectomy in Department of
      Urology, Third Affiliated Hospital of Sun Yat-Sen University from November 2010
      to June 2015 were retrospectively reviewed. The age was (M(QR)) 64 (10) years
      (range 47 to 70 years). The median preoperative serum total prostate specific
      antigen (PSA) level was 7.9 (2.9) MUg/L (range 4.2 to 9.8 MUg/L). The clinical
      TNM stage comprised 24 cases of cT1c and 15 cases of cT2a. All the transrectal
      biopsy Gleason score <=6. The International Index of Erectile Function (IIEF-5)
      was (21.7+/-1.6) points (range 18 to 24 points). The surgical procedures were
      performed through single-site transvesical approach. The postoperative serum PSA
      was regularly detected. The continence status were recorded at 1st month, 3rd
      month and 6th month after catheter removal, and the potencies were evaluated at
      3rd month, 6th month and 12th month postoperative, respectively. Results: All the
      operations were successfully performed and there was no intraoperative
      complication or conversion to standard laparoscopic approach. The operation
      duration was (105+/-26) minuetes, the estimated blood loss was (100+/-56) ml and
      no blood transfusion was required. The pathological TNM stage comprised 30 cases
      of pT2a and 9 cases of pT2b, the Gleason score all <=6 and no patient had
      positive surgical margins. The duration of urinary catheterization was (11.6+/
      1.4) days and hospital stay was (12.9+/-4.3) days. The continence rates were
      84.6%, 97.4%, 100% at 1st month, 3rd month and 6th month after catheter removal,
      respectively. The potency rates were 48.7%, 64.1%, 76.9% at 3rd month, 6th month
      and 12th month postoperative, respectively, with an IIEF-5 score>=18. Two cases
      demonstrated biochemical recurrence and one case presented vesico-urethral
      stricture during an average follow-up of 39 months (range 12 to 60 months).
      Conclusions: TVSSLRP is suitable for low-risk organ-confined prostate cancer. It
      can provide satisfactory continence and potency recovery, less complications and
      good oncological results.

PMID- 27686639
TI  - [Surgical outcomes after laparoscopy-assisted distal gastrectomy and open distal
      gastrectomy for patients with advanced gastric cancer: a case-control study using
      a propensity score method].
AB  - Objective: To investigate the surgical outcomes after the laparoscopy-assisted
      distal gastrectomy (LADG) for patients with advanced gastric cancer. Methods: The
      data of 213 patients who underwent LADG and 213 treated by open distal
      gastrectomy (ODG) were selected using the propensity score matching method from a
      prospectively constructed database of 641 patients who underwent radical distal
      gastrectomy between January 2005 and June 2012 in Department of Gastric Surgery,
      Fujian Medical University Union Hospital. The baseline characteristics and
      surgical outcomes were compared using a paired t-test or the Wilcoxon signed
      ranks test for continuous variables. The cumulative survival rates were compared
      using the Kaplan-Meier method and log-rank test. Results: Among all patients,
      there were significant differences in tumor location, digestive tract
      reconstruction, histologic type, pT stage, and pTNM stage between LADG and ODG
      group (P<0.05). After propensity score matching, patient distributions were
      closely balanced. There was no significant difference in clinicopathologic
      characteristics between the two groups (P>0.05). Regarding perioperative
      characteristics, the time to first flatus, and time to resumption of diet, did
      not differ between the two groups (P>0.05), while there were significant
      differences in the operation time (t=-11.28, P=0.000), blood loss (t=-5.674,
      P=0.000), number of dissected lymph nodes (t=4.727, P=0.000), and post-operative
      hospital stay (t=-2.193, P=0.038). LADG group has less morbidity than ODG group
      (chi2=4.777, P=0.029). Multivariate analysis revealed that the laparoscopic
      surgery (RR=0.392, P=0.009) was the protected factor for determining
      postoperative complications. There was no significant difference in the
      cumulative survival rate at total and each UICC stage between the two groups,
      either (P>0.05). Conclusion: LADG is an oncological safe minimally invasive
      procedure for advanced gastric cancer yields comparable oncological outcomes with
      ODG.

PMID- 27686640
TI  - [Endovascular repair of primary retrograde Stanford type A aortic dissection].
AB  - Objective: To summarize the short- and mid-term results on endovascular repair of
      primary retrograde Stanford type A aortic dissection with an entry tear in distal
      aortic arch or descending aorta. Methods: Between December 2009 and December
      2014, 21 male patients of primary retrograde Stanford type A aortic dissection
      with a mean age of (52+/-9) years received endovascular repair in Department of
      Cardiothoracic Surgery, Jinling Hospital. Among the 21 cases, 17 patients were
      presented as ascending aortic intramural hematoma, 4 patients as active blood
      flow in false lumen and partial thrombosis, 8 patients as ulcer on descending
      aorta combined intramural hematoma in descending aorta, and 13 patients as
      typical dissection changes. All patients received endovascular stent-graft repair
      successfully, with 15 cases in acute phase and 6 cases in chronic phase. Results:
      Cone stent was implanted in 13 cases, while straight stent in 8 cases, including
      1 case of left common carotid-left subclavian artery bypass surgery and 1 case of
      restrictive bare-metal stent implantation. No perioperative stroke, paraplegia,
      stent fracture or displacement, limbs or abdominal organ ischemia or other severe
      complications occured, except for tracheotomy in 2 patients. Active blood flow in
      ascending aorta or aortic arch disappeared, and intramural hematoma started being
      absorbed on CT angiography images before discharge. All patients were alive
      during follow-up (6 to 72 months), and intramural hematoma in ascending aorta and
      aortic arch was absorbed thoroughly. Type I endoleak and ulcer expansion were
      found in 1 patient, and type IV endoleak in distal stent was found in another one
      patient. Secondary ascending aortic dissection was found in 1 case two years
      later, which was cured by hybrid procedure with cardiopulmonary bypass.
      Conclusion: Endovascular repair of primary retrograde Stanford type A aortic
      dissection was safe and effective, which correlated with favorable short- and mid
      term results.

PMID- 27686641
TI  - [Clinical effect of compound internal fixations in treating extreme distal radial
      fractures].
AB  - Objective: To investigate the clinical character and treating strategy of extreme
      distal radial fractures. Methods: From June 2012 to May 2014, 12 patients who
      suffered from extreme distal radial fractures were treated in Department of
      Orthopedics, Tongji Hospital, Tongji University. According to AO/OTA
      classification, there were 4 cases of type 23B1, 3 cases of 23B2, 3 cases of 23C1
      and 2 cases of 23C3.When classified by morphological features, there were 4 of
      simple styloid process fracture, 3 of simple extreme distal radial fracture
      without articular surface involved, 3 of styloid process fracture combined with
      distal radial articular fracture, and 2 of articular surface splintered or
      collapse fracture. According to the fracture features that radiographic exams
      showed, different surgical paths and fixation methods were chosen in order to
      protect soft tissues to the best advantage. To those patients with simple styloid
      process fracture, screw alone, Kirschner-wire or styloid plate were used for
      fixation. To the other types of fracture, open reduction and compound internal
      fixation with low-notch volar plate, dorsal or volar mini-plate, screw or
      Kirschner-wire was applied to ensure the stability of fixation, and maximally
      protect soft tissues like tendons, ligaments and neurovascular bundles, counting
      on the "stuffing-squeezing" effects after reduction or reconstruction of the
      articular surface. Situation of the wound and soft tissue were mainly checked in
      the first 2 weeks, and in the 3rd month post-operatively, fracture reduction and
      internal fixation were evaluated by radiographic methods like X-ray and CT scan.
      When 12 months post-operatively, not only radiographic follow-up such as fracture
      reduction, internal fixation and osteoarthritis were taken, but also some other
      evaluation, such as pain of wrist, rotation range of forearm, grip strength, and
      function of wrist according to DASH scores. Results: All of the 12 cases were
      followed up for at least 1 year. The wound healed well in all cases 2 weeks post
      operatively, and no soft tissue infections, necrosis or neurovascular
      complications occurred. All fractures healed and no loss of reduction occurred 3
      months post-operatively. Internal fixations were at good condition except in 2
      cases, whose Kirschner-wire had been removed 2.5 and 2.8 months after the
      operation due to loosening and partly backing out on dorsal side. When followed
      up at 12 months post-operatively, one from these 2 patients suffered from a mild
      pain of wrist, and grip strength together with the function of the affected wrist
      dramatic declined when compared to the unaffected side. With the help of
      radiograph, local collapse on the articular surface was found, which meant to be
      traumatic arthritis. There were no pain in the rest 11 cases, and flexion
      extension range of the wrist, rotation range of forearm and grip strength of the
      affected side recovered to over 80% of the unaffected side, with a DASH score was
      from 7 to 15 points(average 11.9 points)below 15 points. Conclusions: Traditional
      volar plates can not be used for extreme distal radial fractures. It may be an
      effective way to treat extreme distal radial fractures with compound internal
      fixation on the basis of morphological feature of fractures and the situation of
      soft tissue because of vivid of the fixation, reducing damage of soft tissue and
      early functional training.

PMID- 27686642
TI  - [Random clinical study about application value of oxycodone in radiofrequency
      ablation of hepatocellular carcinoma].
AB  - Objective: To evaluate the clinical effect and safety of oxycodone hydrochloride
      in the anesthesia for percutaneous radiofrequency ablation (PRFA) in
      hepatocellular carcinoma. Methods: Between March and December 2015, 60 cases of
      hepatocellular carcinoma patients undergoing percutaneous radiofrequency ablation
      surgery in Peking University Cancer Hospital were randomly divided into three
      groups: oxycodone group (group Q), fentanyl group (group F) and dezocine group
      (group D), 20 cases in each group. Respectively intravenously injection oxycodone
      0.1 mg/kg, fentanyl 0.001 mg/kg, dezocine 0.1 mg/kg before surgery. After the
      surgeon completed puncture administer propofol to maintain anesthesia. Recorded
      mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), oxygen
      saturation (SpO2) changes in each group at entrance, beginning of radiofrequency
      ablation (T1), radiofrequency ablation began after 10 minutes (T2), the end of
      the surgical and awake. Observe the analgesia effect, respiratory depression,
      nausea, vomit and other complications. Postoperative pain scores were
      recorded.Using ANOVA, repeated measure variance analysis, SNK test, chi2 test and
      other tests to evaluate the anesthetic effect indexes. Results: The observation
      completed in all patients. Patients of three groups had no significant
      differences in general information. No significant difference between MAP, HR and
      SpO2 at each time points among the three groups. At the T1 time point (group Q:
      (11.7+/-1.6)/min, group D: (12.1+/-1.7)/min, group F: (10.3+/-2.3)/min, F=5.068,
      P=0.009) and T2 time point (group Q: (11.9+/-1.3)/min, group D: (12.2+/-1.4)/min,
      group F: (10.7+/-1.3)/min, F=7.024, P=0.002), RR in group F were lower than in
      group Q and group D. Pain visual analogue scores after waking (group Q: 0.2+/
      0.7, group D: 0.3+/-0.7, group F: 1.7+/-1.5, F=12.981, P=0.000) and postoperative
      pain score of 1 hour (group Q: 2.0+/-0.9, group D: 1.8+/-0.8, group F: 4.3+/-0.9,
      F=42.362, P=0.000) in the group Q and group D were significantly lower than in
      group F. The body movements in group Q and group D were significantly less than
      in group F (3 cases, 3 cases, 9 cases, chi2=6.400, P=0.041 ). Intraoperative
      respiratory depression in group Q and group D were lower than group F (3 cases, 2
      cases, 9 cases, chi2=8.012, P=0.018). Conclusions: Oxycodone hydrochloride can be
      used safely and effectively for radiofrequency ablation. It has favorable
      hemodynamic stability, lower incidence of respiratory depression, and advantage
      in terms of postoperative pain.

PMID- 27686643
TI  - [The application effect of traditional monitoring and self-monitoring methods in
      oral anticoagulant patients with mechanical valve replacement patients: a meta
      analysis].
AB  - Objective: To evaluate the effects of traditional monitoring and self-monitoring
      in patients who take the oral anticoagulation medicine after mechanical valve
      replacement surgical operations. Methods: A great number of Chinese and English
      literatures about this subject were investigated in detail, and these literatures
      were selected from the Cochrane Central Register of Controlled Trials, EMBase,
      MEDLINE, Web of Knowledge, CNKI, CBM, VIP, and WanFang Data. It should be noted
      that all of the literatures were published before October, 2015. Based on the
      results of the literature investigation, several studies were selected as the
      candidates. Moreover, many aspects about these candidates such as the
      experimental designs, characteristics of the objects of the studies and the
      results of the studies were filtered and recorded by two researchers
      independently. Furthermore, RevMan 5.3 were employed to analyze the data of the
      candidates. Results: Eight randomized controlled trials were studied, which
      included 1 262 cases in self-monitoring group and 1 198 cases in traditional
      monitoring group. The results of meta-analysis indicated that compared with the
      traditional monitoring group, lower incidence of thromboembolism (Z=3.50,
      P=0.000) and lower mortality (Z=4.64, P=0.000) were observed, and the bleeding
      difference (Z=0.07, P=0.940) had no significant statistical meaning. Moreover,
      compared with the traditional monitoring, the international normalized ratio
      (INR) of the patients who were controlled in the range of treatment of the self
      monitoring increased from 6% to 20.9%, and the total number of the INR tests was
      increased by 2.1 to 4.98 times. Conclusions: Self-monitoring could obviously
      reduce the possibilities of the thromboembolism and death of the patients who
      took the oral anticoagulation medicine after mechanical valve replacement
      surgical operations. Furthermore, self-monitoring could not only control the INR
      in the range of treatment but also increase the total number of the INR tests. In
      short, self-monitoring has practical value of clinical application.

PMID- 27686644
TI  - [New progress of castration-resistant prostate cancer immunotherapy].
AB  - Prostate cancer, especially castration-resistant prostate cancer (CRPC) with its
      very poor prognosis, quite difficult treatments and urgent need of new theraputic
      strategies has become a serious problem of men's health in our country. Recent
      studies have shown that prostate cancer cells can stimulate the immune response;
      therefore, immunotherapy has become one of the hot spots in the treatment of
      CRPC. Cancer vaccines including polypeptide vaccines, nucleic acid vaccines,
      whole cell vaccines and autologous dendritic cell vaccines have been in stage II
      or III clinical trials, and will have good application prospects. Immune
      checkpoint inhibitors for the treatment of melanoma have got satisfactory
      results, but for CRPC are lack of systematic researches and the effects remain to
      be followed-up. Immune modulators for CRPC have shown antitumor activity, but the
      overall survival of patients was not improved. Existing studies have shown that
      immunotherapy of CRPC has good prospects, but most drugs are still in the
      research stage and need a considerable distance before clinical application. The
      optimal timing of immunotherapy, value of combined administration, evaluation of
      therapeutic effect, potential immune-based predictive and prognostic biomarkers
      are to be explored. With the development of tumor immune agents and the
      accumulation of evidence based medicine, CRPC immunotherapy will be more
      standard.

PMID- 27686645
TI  - [Recent progress in MRI-ultrasound fusion for guidance of targeted prostate
      biopsy].
AB  - Prostate cancer is currently diagnosed by prostate biopsy performed by the
      transrectal ultrasound-guided technique. However, overdetection of clinical
      insignificant tumours and missed detection of clinical significant tumours have
      become problematic. MRI of the prostate, particularly if performed with
      multiparametric imaging, is capable of detecting clinical significant prostate
      cancer, which has brought the opportunity to use those images as targets for
      needle biopsy. Three methods of fusing MRI for targeted biopsy have been recently
      described: MRI-ultrasound fusion, MRI-MRI fusion ('in-bore' biopsy) and cognitive
      fusion. Fusion of MRI with ultrasound allows urologists to progress from blind,
      systematic biopsies to biopsies, which are mapped, targeted and tracked. In the
      future, MRI-ultrasound fusion for lesion targeting is likely to result in fewer
      and more accurate prostate biopsies than the present use of systematic biopsies
      with ultrasound guidance alone.

PMID- 27686646
TI  - [Progress of application for enhanced recovery after surgery in
      pancreaticoduodenectomy].
AB  - Due to the large surgical trauma and postoperative complications, the
      perioperative management of pancreaticoduodenectomy has been one of the urgent
      problems to be solved by the surgeons. With the development of modern medicine,
      enhanced recovery after surgery (ERAS) comes into being, basing on anti-stress
      mechanism and multi-disciplinary team, and the perioperative management of
      pancreaticoduodenectomy has been optimized and improved continuously. The
      surgeons through a range of measures that had evidence-based medicine basis to
      mitigate the extent of surgical trauma stress, reduce the incidence of
      postoperative complications, shorten patient recovery time previously healthy
      state, and achieve maximize benefit for patients. Currently, the ERAS application
      in the specific aspects of pancreaticoduodenectomy remains contentious. However,
      with the emergence of evidence-based medicine, ERAS is constantly being refined.
      Therefore, this article combined with ERAS guidelines and expert consensus is of
      great significance to deepen the research and understanding of ERAS in
      pancreaticoduodenectomy.

PMID- 27686648
TI  - Telehealth interventions for reducing waiting lists and waiting times for
      specialist outpatient services: A scoping review.
AB  - We undertook a scoping review of the published literature to identify and
      summarise key findings on the telehealth interventions that influence waiting
      times or waiting lists for specialist outpatient services. Searches were
      conducted to identify relevant articles. Articles were included if the telehealth
      intervention restructured or made the referral process more efficient. We
      excluded studies that simply increased capacity. Two categories of interventions
      were identified - electronic consultations and image-based triage. Electronic
      consultations are asynchronous, text-based provider-to-provider consultations.
      Electronic consultations have been reported to obviate the need for face-to-face
      appointments between the patient and the specialist in between 34-92% of cases.
      However, it is often reported that electronic consultations are appropriate in
      less than 10% of referrals for outpatient care. Image-based triage has been used
      successfully to reduce unnecessary or inappropriate referrals and was used most
      often in dermatology, ophthalmology and otolaryngology (ENT). Reported reduction
      rates for face-to-face appointments by specialty were: dermatology 38-88%,
      ophthalmology 16-48% and ENT 89%. Image-based triage can be twice as effective as
      non-image based triage in reducing unnecessary appointments. Telehealth
      interventions can effectively be used to reduce waiting lists and improve the
      coordination of specialist services, and should be considered in conjunction with
      clinical requirements.

PMID- 27686647
TI  - Cutaneous nodular fasciitis with genetic analysis: a case series.
AB  - Nodular fasciitis is a benign self-limited myofibroblastic neoplasm, which
      usually involves the upper extremities and trunk of young patients. These tumors
      have been shown to harbor a translocation involving the MYH9 and USP6 genes,
      leading to overexpression of the latter. We report seven cases of nodular
      fasciitis with cutaneous presentations. All cases involved the dermis, with six
      involving the superficial subcutis, and one auricular tumor extending into
      cartilage. All cases showed USP6 rearrangement by fluorescence in situ
      hybridization; in two of three cases, the characteristic MYH9-USP6 fusion was
      shown by RT-PCR. All patients underwent conservative resection. Nodular fasciitis
      is an uncommon mesenchymal neoplasm that can occasionally present in superficial
      locations and is sometimes mistaken for a malignant process. Molecular testing
      can be useful to distinguish this entity from other cutaneous spindle cell
      tumors.

PMID- 27686650
TI  - David Oliver: Frailty in acute care.

PMID- 27686649
TI  - Association of Mycobacterium infections in patients with Mendelian susceptibility
      to mycobacterial disease with venous thromboembolism.
AB  - An association between a hypercoagulable state and Mendelian susceptibility to
      mycobacterial disease (MSMD) has been established in a few studies; resultant
      thrombosis is considered rare. In a case-control study, the prevalence of factor
      V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR)
      C677T, A1298C mutations were investigated in mycobacterium-infected patients. The
      study comprised 30 patients with mycobacterial infections (invasive, disseminated
      and/or recurrent infections with Bacille Calmette-Guerin or non-tuberculosis
      mycobacteria and Mycobacterium Tuberculosis with positive results for acid-fast
      bacilli and tuberculin skin tests) and 30 normal healthy controls. Forty female
      (66.7%) and 20 male subjects (33.3%) aged from 3 to 70 years were recruited into
      this study. Genotyping of targeted genes was performed by RT-PCR and cytokine TNF
      alpha concentrations were quantified using a commercially available ELISA kit.
      Significant associations between mycobacterial infection and TNF-alpha production
      after stimulating peripheral blood mononuclear cells with LPS alone and with IFN
      gamma plus LPS were identified. Moreover, genotyping analysis in the studied
      population revealed a significant association between MTHFR c.677C>T (OR, 3.28;
      95% CI, 1.35-7.92; P < 0.05), MTHFR c.1298A>C (OR, 2.33; 95% CI, 1.10-4.93; P <
      0.05) and mycobacterial infection in affected patients, indicating susceptibility
      to venous thromboembolism according to previous studies. Additionally,
      mycobacterium-infected patients had a significantly greater prevalence of MTHFR
      C677T and A1298C mutations than controls.

PMID- 27686651
TI  - Value of video monitoring for nocturnal seizure detection in a residential
      setting.
AB  - OBJECTIVE: Following a sudden death at a residential care unit, the Dutch Health
      and Care Inspectorate advised intensification of the use of video monitoring (VM)
      at the unit. We assessed whether VM resulted in increased identification of
      seizures that required clinical intervention. METHODS: The unit provides care for
      340 individuals with refractory epilepsy and severe learning disabilities.
      Acoustic detection systems (ADSs) cover all individuals; 37 people also have a
      bed motion sensor (BMS) and 46 people with possible nocturnal seizures are now
      monitored by VM. During a 6-month period, in all cases of a suspected seizure we
      asked the caregivers to specify which device alerted them and to indicate whether
      this led to an intervention. Staff costs of VM were estimated using payroll
      information. RESULTS: We identified 1,208 seizures in 37 individuals: 4 had no
      nocturnal seizures and 393 (33%) seizures were seen only on video. In 169 (14%)
      of 1,208 seizures an intervention was made and this included 39 (10%) of 393
      seizures seen only on video. When compared to seizures observed with an ADS or
      BMS, seizures seen only on video were more often tonic seizures (71% vs. 22%, p <
      0.001) and occurred mostly in the beginning or at the end of the night (40% vs.
      26%, p < 0.001). The extra staff costs of monitoring was 7,035 euro per seizure
      seen only on video and leading to an intervention. SIGNIFICANCE: VM facilitates
      nocturnal surveillance, but the costs are high. This underscores the need for
      development of reliable seizure detection devices.

PMID- 27686652
TI  - Developing immunotherapies for childhood cancer.

PMID- 27686653
TI  - Available Evidence on Leber Congenital Amaurosis and Gene Therapy.
AB  - Leber congenital amaurosis (LCA) is a group of severe inherited retinal
      dystrophies that lead to early childhood blindness. In the last decade, interest
      in LCA has increased as advances in genetics have been applied to better
      identify, classify, and treat LCA. To date, 23 LCA genes have been identified.
      Gene replacement in the RPE65 form of LCA represents a major advance in
      treatment, although limitations have been recognized. In this article, we review
      the clinical and genetic features of LCA and evaluate the evidence available for
      gene therapy in RPE65 disease.

PMID- 27686654
TI  - Structural Insights into IRE1 Functions in the Unfolded Protein Response.
AB  - IRE1 signaling is the most evolutionarily conserved branch in the UPR. IRE1 is an
      ER stress sensor and provides a structure-based platform for the unfolded
      proteins docking, which causes the luminal domain conformational change and
      oligomerization. This selfassociation of IRE1 facilitates the phosphorylation of
      activation loop, which unlocks the autoinhibition in the kinase domain. The
      activating mechanistic cascade is thus initiated to induce DFG-in conformational
      change and movement of alphaC-helix to the active site. Structurally, RNase
      activity is coupled to autophosphorylation and activation of kinase domain.
      Consequently, the activation of RNase domain in human IRE1 indicates the
      conformational rearrangement switching the structural arranging pattern from face
      to-face to back-to-back. IRE1 is still under investigation for target-specific
      drug development. Two types of ATP-competitive inhibitors of IRE1 kinase are
      introduced to modify RNase activity, regulating the UPR in response to ER stress.
      However, once the high activation of RNase surpasses the threshold, its
      biological roles will switch from adaption to destruction. This might explain for
      the dual functions of IRE1 in pro-survival and pro-apoptosis. Structural and
      mechanistic studies of IRE1 highlight the challenge of controlling the UPR in
      diseases.

PMID- 27686655
TI  - Anti-cancer Drug Delivery Using Metal Organic Frameworks (MOFs).
AB  - Cancer is the uncontrolled growth of cells in the body and is considered as one
      of the major causes of death globally. There are several cytotoxic
      chemotherapeutic agents used to treat cancer including methotrexate, 5
      fluorouracil, cisplatin, tamoxifen, doxorubicin and others. Although billions of
      dollars have been spent on cancer research to develop these chemotherapies, it
      still remains a major illness for mankind partly due to the shortcomings of these
      therapies. These shortcomings include low targeting specificity, severe side
      effects (due to high doses) and poor pharmacokinetics. To avoid these drawbacks,
      anti-cancer drug delivery systems have been developed recently using nanocarriers
      including liposomes, micelles, polyelectrolyte capsules and others. One of the
      recent class of nanoparticles investigated for chemotherapeutic use are metal
      organic frameworks (MOFs) which are hybrid polymers that consist of metal ions or
      clusters and organic ligands. MOFs are used in many applications including
      gas/vapor separation, gas storage, catalysis, luminescent materials, and
      biomedical imaging. These structures have additional features that promote their
      use as drug carriers in the biomedical field. First, they are nontoxic,
      biodegradable and have the ability to carry high loadings of the anti-neoplastic
      agent due to their porous nature. Also, they have well-defined crystalline
      structures that can be characterized by different analytical techniques and their
      sizes are suitable to control their in vivo drug release. This paper reviews the
      methods used to synthesize MOFs and their recent use as antineoplastic drug
      delivery carriers.

PMID- 27686656
TI  - MDM2 Increases Drug Resistance in Cancer Cells by Inducing EMT Independent of
      p53.
AB  - Mdm2 is a well studied oncogene and has been reported to be closely related to
      chemoresistance in different manners. In this article, we discuss the current
      knowledge of mdm2's function in drug resistance, the novel relationship between
      MDM2 and Akt phosphorylation, the role of Akt signaling pathway in epithelial
      mesenchymal transition, and the positive correlation among MDM2, epithelial
      mesenchymal transition and drug resistance. We propose a possible pathway by
      which MDM2 increases drug resistance through inducing epithelial-mesenchymal
      transition independent of p53. This pathway may play a significant role in the
      tumorigenesis and chemoresistance. By targeting MDM2, we can re-activate the
      function of p53, inhibit the epithelial-mesenchymal transition process and thus
      increase cancer cells sensitivity to chemotherapy. Thus, from p53-dependent and
      p53-independent aspects, it may present a better strategy for cancer treatment
      than targeting other genes.

PMID- 27686657
TI  - Overview of Systems Biology and Omics Technologies.
AB  - Traditional technologies using reductionist approach are relatively insufficient
      to solve problems in a biological system. Rather than a reductionist approach,
      systems biology uses a holistic and integrative approach to better figure out the
      whole process. Both qualitatively and quantitatively of biological system provide
      information about diseases, toxicities, therapies etc. Omics technologies, which
      systems biology brings, are valuable tools for comprehensive analyses. Automated
      DNA sequencers enabled the sequencing of genomes; microarray and mass
      spectrometry analysis permit global transcriptional profiling and lead to large
      scale proteomic and metabolomics analysis. These high-throughput data need to be
      interpreted by bioinformatics. So far there has been no concrete published paper
      that compiles omics technologies according to PubMed database. In the present
      review, it was aimed to give brief description of systems biology and information
      on the advantages and disadvantages of omics technologies.

PMID- 27686658
TI  - Alterations in Cerebral Cortical Glucose and Glutamine Metabolism Precedes
      Amyloid Plaques in the APPswe/PSEN1dE9 Mouse Model of Alzheimer's Disease.
AB  - Alterations in brain energy metabolism have been suggested to be of fundamental
      importance for the development of Alzheimer's disease (AD). However, specific
      changes in brain energetics in the early stages of AD are poorly known. The aim
      of this study was to investigate cerebral energy metabolism in the
      APPswe/PSEN1dE9 mouse prior to amyloid plaque formation. Acutely isolated
      cerebral cortical and hippocampal slices of 3-month-old APPswe/PSEN1dE9 and wild
      type control mice were incubated in media containing [U-13C]glucose, [1,2
      13C]acetate or [U-13C]glutamine, and tissue extracts were analyzed by mass
      spectrometry. The ATP synthesis rate of isolated whole-brain mitochondria was
      assessed by an on-line luciferin-luciferase assay. Significantly increased 13C
      labeling of intracellular lactate and alanine and decreased tricarboxylic acid
      (TCA) cycle activity were observed from cerebral cortical slices of
      APPswe/PSEN1dE9 mice incubated in media containing [U-13C]glucose. No changes in
      glial [1,2-13C]acetate metabolism were observed. Cerebral cortical slices from
      APPswe/PSEN1dE9 mice exhibited a reduced capacity for uptake and oxidative
      metabolism of glutamine. Furthermore, the ATP synthesis rate tended to be
      decreased in isolated whole-brain mitochondria of APPswe/PSEN1dE9 mice. Thus,
      several cerebral metabolic changes are evident in the APPswe/PSEN1dE9 mouse prior
      to amyloid plaque deposition, including altered glucose metabolism, hampered
      glutamine processing and mitochondrial dysfunctions.

PMID- 27686659
TI  - Increased Expression of Slit2 and its Robo Receptors During Astroglial Scar
      Formation After Transient Focal Cerebral Ischemia in Rats.
AB  - Slit2, a secreted glycoprotein, has recently been implicated in the post-ischemic
      astroglial reaction. The objective of this study was to investigate the temporal
      changes and cellular localization of Slit2 and its receptors, Robo1, Robo2, and
      Robo4, in a rat transient focal ischemia model induced by middle cerebral artery
      occlusion. We used double- and triple-immunolabeling to determine the cell
      specific changes in Slit2 and its receptors during a 10-week post-ischemia
      period. The expression profiles of Slit2 and the Robo receptors shared
      overlapping expression patterns in sham-operated and ischemic striatum.
      Constitutive expression of Slit2 and Robo receptors was observed in striatal
      neurons with weak intensity, whereas in rats reperfused after ischemic insults,
      these immunoreactivities were increased in reactive astrocytes. Astroglial
      induction of Slit2 and Robo in the peri-infarct region was distinct on days 7-14
      after reperfusion and thereafter increased progressively throughout the 10-week
      experimental period. Slit2 and Robo were prominently expressed in the perinuclear
      cytoplasm and main processes of reactive astrocytes forming the astroglial scar.
      This observation was confirmed by quantification of the mean fluorescence
      intensity of Slit2 and Robo receptors over reactive astrocytes localized at the
      edge of the infarct area. However, activated microglia/macrophages in the peri
      infarct area were devoid of any specific labeling for Slit2 and Robo. Thus, our
      data revealed a selective and sustained induction of Slit2 and Robo in astrocytes
      localized throughout the astroglial scar after ischemic stroke, suggesting that
      Slit2/Robo signaling participates in glial scar formation and brain remodeling
      following ischemic injury.

PMID- 27686660
TI  - Neuroprotective Effects of Theaflavins Against Oxidative Stress-Induced Apoptosis
      in PC12 Cells.
AB  - Oxidative stress can induce neuronal apoptosis via the production of superoxide
      and hydroxyl radicals. This process is as a major pathogenic mechanism in
      neurodegenerative disorders. In this study, we aimed to clarify whether
      theaflavins protect PC12 cells from oxidative stress damage induced by H2O2. A
      cell model of PC12 cells undergoing oxidative stress was created by exposing
      cells to 200 MUM H2O2 in the presence or absence of varying concentrations of
      theaflavins (5, 10, and 20 MUM). Cell viability was monitored using the MTT assay
      and Hoechst 33258 staining, showing that 10 MUM theaflavins enhanced cell
      survival following 200 MUM H2O2 induced toxicity and increased cell viability by
      approximately 40 %. Additionally, we measured levels of intracellular reactive
      oxygen species (ROS) and antioxidant enzyme activity. This suggested that the
      neuroprotective effect of theaflavins against oxidative stress in PC12 cells is
      derived from suppression of oxidant enzyme activity. Furthermore, Western blot
      analyses indicated that theaflavins downregulated the ratio of pro-apoptosis/anti
      apoptosis proteins Bax/Bcl-2. Theaflavins also downregulated the expression of
      caspase-3 compared with a H2O2-treated group that had not been treated with
      theaflavins. Interestingly, this is the first study to report that the four main
      components of theaflavins found in black tea can protect neural cells (PC12) from
      apoptosis induced by H2O2. These findings provide the foundations for a new field
      of using theaflavins or its source, black tea, in the treatment of
      neurodegenerative diseases caused by oxidative stress.

PMID- 27686661
TI  - Lidocaine controls pain and allows safe wound bed preparation and debridement of
      digital ulcers in systemic sclerosis: a retrospective study.
AB  - In Systemic Sclerosis (SSc), digital ulcers (DU) are painful, difficult to heal,
      and frequently infected. To reduce the risk of bacterial infection and to prevent
      chronicity, it is essential to carefully remove necrotic tissue from DU, with
      maximum patient comfort. Debridement, although very efficacious, is invasive and
      causes local pain: lidocaine is a local anesthetic commonly used as to fight pain
      during debridement procedures. The aim of the study was to evaluate the efficacy
      of lidocaine 4 % in pain control during debridement procedure of DU in SSc. One
      hundred eight DU characterized by pain Numeric Rating Scale (NRS) >3/10 before
      starting the procedure were treated with lidocaine 4 % (lidocaine cloridrate 200
      mg in 5 ml of injecting solution). Pain was measured with NRS (0-10) before
      starting debridement, after 15 min of lidocaine application and at the end of the
      procedure. In DU, in respect to baseline (mean NRS 6.74 +/- 2.96), pain after
      application of lidocaine 4 % for 15 min was significantly lower (mean NRS 2.83 +/
      2.73) (p < 0.001). At the end of the procedure, pain control was still
      maintained and significantly lower (mean NRS 2.88 +/- 2.65) in respect to
      baseline (p < 0.001). No systemic adverse event due to topical lidocaine were
      observed. In SSc, topical application of lidocaine 4 % significantly reduces
      pain, allowing a safe debridement procedure, thus improving the management of DU.

PMID- 27686663
TI  - Effects of Mydrin eye-drops on central corneal thickness values in adult patients
      with myopia.
AB  - OBJECTIVE: This study aimed to evaluate the effect of Mydrin eye-drops on central
      corneal thickness values and investigate the duration of the effect. METHODS: In
      this prospective randomised self-controlled study, we enrolled 60 myopic patients
      (120 eyes) undergoing corneal laser refractive surgery. The central corneal
      thickness was measured before and one and four hours after administration of
      Mydrin eye-drops (major components are tropicamide and phenylephrine
      hydrochloride) using the Orbscan II anterior segment analysis system and a SP
      2000P non-contact specular microscope, respectively. RESULTS: Using the Orbscan
      II system, the baseline central corneal thickness (545 +/- 27 um) was
      significantly lower than that at one hour after Mydrin eye-drop application (559
      +/- 31 um; p < 0.001); it was comparable to that at four hours post-Mydrin eye
      drop administration (544 +/- 26 um; p < 0.74). Measured by non-contact specular
      microscopy, the baseline central corneal thickness (508 +/- 26 um) was
      significantly lower than that at one hour after Mydrin eye-drop application (521
      +/- 29 um; p < 0.001); it was comparable to that at four hours after Mydrin eye
      drop administration (506 +/- 24 um; p = 0.62). A significant difference was
      observed in the central corneal thickness at one and four hours after Mydrin eye
      drop application by both methods (p < 0.001). Bland-Altman plots showed agreement
      between the measurements by the two methods at different times. CONCLUSION:
      Central corneal thickness increases one hour after topical application of Mydrin
      eye-drops and is normalised at four hours following the administration of the
      drops. For patients scheduled to undergo excimer laser corneal refractive
      surgery, the central corneal thickness should be measured before or four hours
      after administration of Mydrin eye-drops.

PMID- 27686662
TI  - Different roles of TNF inhibitors in acute anterior uveitis associated with
      ankylosing spondylitis: state of the art.
AB  - The purpose of the present review was to provide a comprehensive picture of the
      efficacy of the different tumor necrosis factor (TNF)-alpha inhibiting agents in
      the treatment of acute anterior uveitis (AAU), the most common extra-articular
      manifestation of ankylosing spondylitis (AS). AS related, AAU may lead to severe
      visual impairment, due to frequent flare recurrences, anterior, and posterior
      segment complications and traditional treatment side effects. Considerably higher
      levels of tumor necrosis factor (TNF) have been assessed in the aqueous humor and
      inflamed joints of patients with AS. Anti-TNF drugs have shown efficacy in
      preventing relapses of rheumatological manifestations of spondyloarthropathies.
      Several studies have underlined the sustained efficacy of the monoclonal anti-TNF
      antibodies also in reducing the recurrence of anterior chamber flares in patients
      with AS-related AAU. On the other hand, retrospective studies and observational
      reports have indicated lower effectiveness and some paradoxical occurrence of
      uveitis following treatment with the soluble receptor agent etanercept. Growing
      evidence suggests that a prophylactic strategy could be advocated in subjects
      with frequent and recalcitrant attacks of AS-AAU. In this regard, the
      administration of monoclonal anti-TNF antibodies such as adalimumab (ADA) has
      been shown to significantly reduce the rate of AAU recurrences. Indeed, during
      ADA treatment about 90 % of patients have shown to remain completely free of
      attacks for the entire follow-up period, in most studies. Further studies are
      needed to confirm the long-term efficacy of TNF inhibitors in AS related AAU and
      also their role in preventing ocular complications and visual impairment.

PMID- 27686664
TI  - Investigation of a type C/D botulism outbreak in free-range laying hens in
      France.
AB  - In 2014, a botulism outbreak in a flock of laying hens was investigated in
      France. In the flock of 5020 hens, clinical signs of botulism occurred at 46
      weeks of age. A type C/D botulism outbreak was confirmed using the mouse
      lethality assay for detection of botulinum toxin in serum and a real-time PCR
      test to detect Clostridium botulinum in intestinal contents. The disease lasted
      one week with a mortality rate of 2.6% without recurrence. Botulism in laying
      hens has rarely been reported. Five monthly visits were made to the farm between
      December 2014 and May 2015 for a longitudinal study of the persistence of C.
      botulinum in the poultry house after the outbreak, and to assess egg
      contamination by C. botulinum. Several samples were collected on each visit: in
      the house (from the ventilation circuit, the egg circuit, water and feed,
      droppings) and the surrounding area. Thirty clean and 30 dirty eggs were also
      swabbed at each visit. In addition, 12 dirty and 12 clean eggs were collected to
      analyse eggshell and egg content. The samples were analysed using real-time PCR
      to detect type C/D C. botulinum. The bacterium was still detected in the house
      more than 5 months after the outbreak, mostly on the walls and in the egg
      circuit. Regarding egg contamination, the bacteria were detected only on the
      shell but not in the content of the eggs. Control measures should therefore be
      implemented throughout the egg production period to avoid dissemination of the
      bacteria, particularly during egg collection.

PMID- 27686665
TI  - Antiinflammatory Effects of Functionally Active Compounds Isolated from Aged
      Black Garlic.
AB  - The antiinflammatory effects of functionally active compounds isolated from aged
      black garlic (AGE-1 and AGE-2) were investigated using a lipopolysaccharide
      induced inflammatory response model. To examine the potential antiinflammatory
      properties of AGE-1 and AGE-2, cell viability as well as nitric oxide,
      prostaglandin E2, and pro-inflammatory cytokine [interleukin-6 (IL-6), TNF-alpha,
      and IL-1beta] levels were measured. The mRNA and protein expression levels of
      inducible nitric oxide synthase and cyclooxygenase-2 were detected by reverse
      transcription polymerase chain reaction and western blotting. The results
      indicated that AGE-1 and AGE-2 were not cytotoxic to macrophages. Nitric oxide
      and prostaglandin E2 levels decreased significantly with increasing concentration
      of AGE-1 (IC50  = 29.6 and 1.41 ug/mL, respectively), but not AGE-2. The
      secretion of IL-6, TNF-alpha, and IL-1beta was also suppressed by AGE-1 in a dose
      dependent manner, and inducible nitric oxide synthase and cyclooxygenase-2 mRNA,
      and protein expression decreased with AGE-1 treatment. Furthermore, AGE-1
      attenuated the phosphorylation of the extracellular signal-regulated kinase, p38,
      and c-Jun terminal kinase in lipopolysaccharide-induced RAW264.7 cells. These
      results suggested that compound AGE-1 may have significant effects on
      inflammatory factors and could potentially be used as an antiinflammatory
      therapeutic agent. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27686666
TI  - Pathological complete response after neoadjuvant chemotherapy for rectal cancer
      with synchronous multiple liver metastases: a report of an unusual case.
AB  - BACKGROUND: Systemic chemotherapy for stage IV colorectal cancer has advanced
      markedly in the recent years. We report an unusual case of 13 synchronous liver
      metastases for which a pathological complete response was achieved with
      neoadjuvant chemotherapy (NAC) consisting of a combination of 5-fluorouracil (5
      FU), oxaliplatin, leucovorin (mFOLFOX6), and bevacizumab. CASE PRESENTATION: A 44
      year-old man was diagnosed with colorectal cancer with synchronous liver
      metastases. We resected the primary rectal tumor first. Further, after providing
      NAC for hepatic metastases, lateral segmentectomy and partial resection of the
      liver were performed. The subsequent result was compatible with a complete
      pathological response. The postoperative course was uneventful, and the patient
      is currently alive 5 years after the first surgery without evidence of recurrence
      and without adjuvant chemotherapy. CONCLUSIONS: For patients with initially
      resectable colorectal liver metastases, the survival benefits of NAC are still
      unclear. We report a rare case of 13 synchronous liver metastatic lesions from
      rectal cancer with a complete pathological response after neoadjuvant bevacizumab
      containing chemotherapy.

PMID- 27686667
TI  - Characterization of the functional and anatomical differences in the atrial and
      ventricular myocardium from three species of elasmobranch fishes: smooth dogfish
      (Mustelus canis), sandbar shark (Carcharhinus plumbeus), and clearnose skate
      (Raja eglanteria).
AB  - We assessed the functional properties in atrial and ventricular myocardium (using
      isolated cardiac strips) of smooth dogfish (Mustelus canis), clearnose skate
      (Raja eglanteria), and sandbar shark (Carcharhinus plumbeus) by blocking Ca2+
      release from the sarcoplasmic reticulum (SR) with ryanodine and thapsigargin and
      measuring the resultant changes in contraction-relaxation parameters and the
      force-frequency relationship at 20  degrees C and 30  degrees C. We also examined
      ultrastructural differences with electron microscopy. In tissues from smooth
      dogfish, net force (per cross-sectional area) and measures of the speeds of
      contraction and relaxation were all higher in atrial than ventricular myocardium
      at both temperatures. Atrial-ventricular differences were evident in the other
      two species primarily in measures of the rates of contraction and relaxation.
      Ryanodine-thapsigargin treatment reduced net force and its maximum positive first
      derivative (i.e., contractility), and increased time to 50 % relaxation in atrial
      tissue from smooth dogfish at 30  degrees C. It also increased times to peak
      force and half relaxation in clearnose skate atrial and ventricular tissue at
      both temperatures, but only in atrial tissue from sandbar shark at 30  degrees C;
      indicating that SR involvement in excitation-contraction (EC) coupling is species
      and temperature-specific in elasmobranch fishes, as it is in teleost fishes.
      Atrial and ventricular myocardium from all three species displayed a negative
      force-frequency relationship, but there was no evidence that SR involvement in EC
      coupling was influenced by heart rate. SR was evident in electron micrographs,
      generally located in proximity to mitochondria and intercalated discs, and to a
      lesser extent between the myofibrils; with mitochondria being more numerous in
      ventricular than atrial myocardium in all three species.

PMID- 27686669
TI  - Erratum to: Improving Treatment Response for Paediatric Anxiety Disorders: An
      Information-Processing Perspective.

PMID- 27686668
TI  - Physiological constraints and energetic costs of diving behaviour in marine
      mammals: a review of studies using trained Steller sea lions diving in the open
      ocean.
AB  - Marine mammals are characterized as having physiological specializations that
      maximize the use of oxygen stores to prolong time spent under water. However, it
      has been difficult to undertake the requisite controlled studies to determine the
      physiological limitations and trade-offs that marine mammals face while diving in
      the wild under varying environmental and nutritional conditions. For the past
      decade, Steller sea lions (Eumetopias jubatus) trained to swim and dive in the
      open ocean away from the physical confines of pools participated in studies that
      investigated the interactions between diving behaviour, energetic costs,
      physiological constraints, and prey availability. Many of these studies measured
      the cost of diving to understand how it varies with behaviour and environmental
      and physiological conditions. Collectively, these studies show that the type of
      diving (dive bouts or single dives), the level of underwater activity, the depth
      and duration of dives, and the nutritional status and physical condition of the
      animal affect the cost of diving and foraging. They show that dive depth, dive
      and surface duration, and the type of dive result in physiological adjustments
      (heart rate, gas exchange) that may be independent of energy expenditure. They
      also demonstrate that changes in prey abundance and nutritional status cause sea
      lions to alter the balance between time spent at the surface acquiring oxygen
      (and offloading CO2 and other metabolic by-products) and time spent at depth
      acquiring prey. These new insights into the physiological basis of diving
      behaviour further our understanding of the potential scope for behavioural
      responses of marine mammals to environmental changes, the energetic significance
      of these adjustments, and the consequences of approaching physiological limits.

PMID- 27686670
TI  - Clients' perspective on quality of audiology care: Development of the Consumer
      Quality Index (CQI) 'Audiology Care' for measuring client experiences.
AB  - OBJECTIVE: Clients' perspective on the quality of audiology care has not been
      investigated thoroughly. Research has focused primarily on satisfaction with, and
      limitations of hearing aids. We developed a Consumer Quality Index (CQI)
      questionnaire 'Audiology Care' to systematically assess client experiences with
      audiology care. DESIGN: The CQI Audiology Care was developed in three steps: (1)
      posing open-ended questions through e-mail (n = 14), (2) two small-scale surveys
      assessing psychometric properties of the questionnaire (n = 188) and importance
      of quality aspects (n = 118), and (3) a large-scale survey (n = 1793) assessing
      psychometric properties and discriminatory power of the questionnaire. STUDY
      SAMPLE: People with complex hearing impairments and/or balance and communicative
      disorders who visited an audiology care centre during the past year. RESULTS:
      Important quality aspects were translated into seven reliable scales:
      accommodation and facilities, employees' conduct and expertise, arrangement of
      appointments, waiting times, client participation and effectiveness of treatment.
      Client experiences differed among the participating centres concerning
      accommodation and facilities, arrangement of appointments, waiting times and
      client participation. CONCLUSION: The CQI Audiology Care is a valid and reliable
      instrument to assess clients' experiences with audiology care. Future
      implementation will reveal whether results can be used to monitor and improve the
      quality of audiology care.

PMID- 27686672
TI  - A screening method with lymphocyte percentage and proportion of granular
      lymphocytes in the peripheral blood for large granular lymphocyte (LGL) leukemia.
AB  - Large granular lymphocyte leukemia (LGL-L) is defined morphologically as a group
      of lymphoproliferative disorders, including T-cell large granular lymphocytic
      leukemia (T-LGL-L), chronic lymphoproliferative disorders of NK cells (CLPD-NK),
      and aggressive NK cell leukemia. We investigated the morphological features of
      LGL leukemic cells in LGL-L patients to identify screening methods best suited to
      application in daily clinical practice. LGL leukemic cells were mostly
      indistinguishable from normal LGL; however, we developed a simplified approach to
      distinguishing among these cells, in which lymphocyte  % and the proportion of
      granular lymphocytes among lymphocytes (GL %) can serve as parameters at the cut
      off values of 52 and 50 %, respectively. We confirmed the accuracy of these
      methods in validation groups. It may be useful to evaluate GL % to screen for LGL
      L using a cut-off threshold of 50 when Lym % exceeds 52 in the peripheral blood
      examination in cases in which LGL-L is suspected in daily practice while keeping
      clinical context and the coefficient of variation of these parameters under
      consideration.

PMID- 27686671
TI  - Structural basis of steroid binding and oxidation by the cytochrome P450 CYP109E1
      from Bacillus megaterium.
AB  - : Cytochrome P450 monooxygenases (P450s) are attractive enzymes for the
      pharmaceutical industry, in particular, for applications in steroidal drug
      synthesis. Here, we report a comprehensive functional and structural
      characterization of CYP109E1, a novel steroid-converting cytochrome P450 enzyme
      identified from the genome of Bacillus megaterium DSM319. In vitro and whole-cell
      in vivo turnover experiments, combined with binding assays, revealed that
      CYP109E1 is able to hydroxylate testosterone at position 16beta. Related steroids
      with bulky substituents at carbon C17, like corticosterone, bind to the enzyme
      without being converted. High-resolution X-ray structures were solved of a
      steroid-free form of CYP109E1 and of complexes with testosterone and
      corticosterone. The structural analysis revealed a highly dynamic active site at
      the distal side of the heme, which is wide open in the absence of steroids, can
      bind four ordered corticosterone molecules simultaneously, and undergoes
      substantial narrowing upon binding of single steroid molecules. In the crystal
      structures, the single bound steroids adopt unproductive binding modes
      coordinating the heme-iron with their C3-keto oxygen. Molecular dynamics (MD)
      simulations suggest that the steroids may also bind in ~180 degrees  reversed
      orientations with the C16 carbon and C17-substituents pointing toward the heme,
      leading to productive binding of testosterone explaining the observed regio- and
      stereoselectivity. The X-ray structures and MD simulations further identify
      several residues with important roles in steroid binding and conversion, which
      could be confirmed by site-directed mutagenesis. Taken together, our results
      provide unique insights into the CYP109E1 activity, substrate specificity, and
      regio/stereoselectivity. DATABASE: The atomic coordinates and structure factors
      have been deposited in the Protein Data Bank with accession codes 5L90 (steroid
      free CYP109E1), 5L91 (CYP109E1-COR4), 5L94 (CYP109E1-TES), and 5L92 (CYP109E1
      COR). ENZYMES: Cytochrome P450 monooxygenase CYP109E1, EC 1.14.14.1, UniProt ID:
      D5DKI8, Adrenodoxin reductase EC 1.18.1.6.

PMID- 27686673
TI  - Comparison of cyclosporine and tacrolimus combined with mycophenolate mofetil in
      prophylaxis for graft-versus-host disease after reduced-intensity umbilical cord
      blood transplantation.
AB  - Umbilical cord blood transplantation with a reduced-intensity conditioning
      regimen (RIC-UCBT) is used increasingly in patients who have comorbid organ
      functions and lack human leukocyte antigen-identical donors. We compared the
      outcomes in 35 patients who received mycophenolate mofetil plus cyclosporine
      (MMF/CSP, n = 17) or MMF plus tacrolimus (MMF/TAC, n = 18) for graft-versus-host
      disease (GVHD) prophylaxis after RIC-UCBT. Cumulative incidence of neutrophil
      engraftment was 94 and 89 % in MMF/CSP and MMF/TAC groups, respectively (p =
      0.34). The incidence of pre-engraftment immune reaction did not differ between
      the MMF/CSP (41 %) and MMF/TAC (39 %, p = 1.00) groups; however, patients in the
      MMF/TAC group tended to have a lower incidence of grade II-IV acute GVHD than
      those in MMF/CSP group (28 vs 53 %, p = 0.11). Overall survival (OS) at 1 year
      was 43 and 60 % in MMF/CSP and MMF/TAC groups, respectively (p = 0.39).
      Progression-free survival, non-relapse mortality, and relapse rate were
      comparable between the two groups (p = 0.76, 0.59, and 0.88, respectively). In
      multivariate analyses, MMF/TAC GVHD prophylaxis was closely associated with
      improved OS, but not with incidence of engraftment and acute GVHD. These results
      suggest that more intensive GVHD prophylaxis with MMF/TAC decreased acute GVHD
      without affecting other clinical outcomes, resulting in improved OS after RIC
      UCBT.

PMID- 27686674
TI  - Constitutional t(8;22)(q24;q11.2) that mimics the variant Burkitt-type
      translocation in Philadelphia chromosome-positive chronic myeloid leukemia.
AB  - Constitutional translocations that coincide with t(9;22)(q34;q11.2) may lead to
      unnecessary treatments in chronic myeloid leukemia (CML) patients, as, under the
      standard criteria, a diagnosis of CML with additional chromosomal abnormalities
      indicates an accelerated phase (AP). In the present report, a 47-year-old male
      had pain in the right foot due to gout. Peripheral blood examination showed
      leukocytosis with left shift. Bone marrow aspiration revealed myeloid hyperplasia
      with megakaryocytosis. RT-PCR revealed the major BCR-ABL fusion transcript, and
      CML in the chronic phase was diagnosed, followed by nilotinib treatment. Although
      WBC counts decreased immediately, G-banding analysis showed
      46,XY,t(8;22)(q24;q11.2),t(9;22)(q34;q11.2) [20]. The t(8;22)(q24;q11.2)
      translocation is known to be recurrent in Burkitt's lymphoma. The diagnosis was
      changed to CML in AP, leading to B-lymphoid crisis. Unexpectedly, the karyotype
      was 46,XY,t(8;22)(q24;q11.2) [20] in hematological complete remission, even after
      3 months. Fluorescence in situ hybridization on metaphase spreads revealed the
      MYC signal on the der(22)t(8;22), indicating that the 8q24 breakpoint was
      centromeric to MYC at 8q24.21. G-banding analysis of phytohemagglutinin
      stimulated peripheral blood T-lymphocytes also indicated
      46,XY,t(8;22)(q24.1;q11.2). We conclude that the t(8;22) is constitutional in
      this patient. As the tumor suppressor gene TRC8/RNF139 is disrupted by
      constitutional t(8;22)(q24.13;q11.21) in dysgerminoma, it may be associated with
      the onset of CML.

PMID- 27686676
TI  - Central Nervous System Device Infections.
AB  - Nosocomial meningitis can occur in association with central nervous system (CNS)
      devices such as cerebrospinal shunts or drains, intrathecal pumps, and deep brain
      stimulators and carry substantial morbidity and mortality. Diagnosing and
      treating these infections may be challenging to physicians as cerebrospinal fluid
      cultures may be negative due to previous antibiotic therapy and cerebrospinal
      abnormalities may be secondary to the primary neurosurgical issue that prompted
      the placement of the CNS device (e.g., "chemical meningitis" due to intracranial
      hemorrhage). Besides antibiotic therapy given intravenously and sometimes
      intrathecally, removal of the device with repeat cultures prior to re
      implantation is key in achieving successful outcomes. 

PMID- 27686675
TI  - Progressive Multifocal Leukoencephalopathy in HIV-Uninfected Individuals.
AB  - Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of
      the central nervous system (CNS) caused by the human neurotropic polyomavirus JC
      (JCV). The disease occurs virtually exclusively in immunocompromised individuals,
      and, prior to the introduction of antiretroviral therapy, was seen most commonly
      in the setting of HIV/AIDS. More recently, however, the incidence of PML in HIV
      uninfected persons has increased with broader use of immunosuppressive and
      immunomodulatory medications utilized in a variety of systemic and neurologic
      autoimmune disorders. In this review, we discuss the epidemiology and clinical
      characteristics of PML in HIV-uninfected individuals, as well as diagnostic
      modalities and the limited treatment options. Moreover, we describe recent
      findings regarding the neuropathogenesis of PML, with specific focus on the
      unique association between PML and natalizumab, a monoclonal antibody that
      prevents trafficking of activated leukocytes into the CNS that is used for the
      treatment of multiple sclerosis. 

PMID- 27686678
TI  - Ocular Syphilis: a Clinical Review.
AB  - While ocular syphilis is not a new phenomenon, recent increased rates of new
      diagnoses, especially in human immunodeficiency virus (HIV)-infected persons and
      men who have sex with men, have sparked a new interest in an old disease. This
      article will review the clinical presentation, diagnosis, and treatment of ocular
      syphilis, and provide guidance on management. 

PMID- 27686677
TI  - Laboratory Diagnosis of Central Nervous System Infection.
AB  - Central nervous system (CNS) infections are potentially life threatening if not
      diagnosed and treated early. The initial clinical presentations of many CNS
      infections are non-specific, making a definitive etiologic diagnosis challenging.
      Nucleic acid in vitro amplification-based molecular methods are increasingly
      being applied for routine microbial detection. These methods are a vast
      improvement over conventional techniques with the advantage of rapid turnaround
      and higher sensitivity and specificity. Additionally, molecular methods performed
      on cerebrospinal fluid samples are considered the new gold standard for diagnosis
      of CNS infection caused by pathogens, which are otherwise difficult to detect.
      Commercial diagnostic platforms offer various monoplex and multiplex PCR assays
      for convenient testing of targets that cause similar clinical illness. Pan-omic
      molecular platforms possess potential for use in this area. Although molecular
      methods are predicted to be widely used in diagnosing and monitoring CNS
      infections, results generated by these methods need to be carefully interpreted
      in combination with clinical findings. This review summarizes the currently
      available armamentarium of molecular assays for diagnosis of central nervous
      system infections, their application, and future approaches. 

PMID- 27686679
TI  - Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence
      to regulatory networks.
AB  - Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis due to its
      late clinical presentation and the lack of effective non-surgical therapies.
      Unfortunately, most of the patients are not eligible for curative surgery owing
      to the presence of metastases at the time of diagnosis. Therefore, it is
      important to understand the steps leading to cell dissemination in patients with
      CCA. To metastasize from the primary site, cancer cells must acquire migratory
      and invasive properties by a cell plasticity-promoting phenomenon known as
      epithelial-mesenchymal transition (EMT). EMT is a reversible dynamic process by
      which epithelial cells gradually adopt structural and functional characteristics
      of mesenchymal cells, and has lately become a centre of attention in the field of
      metastatic dissemination. In the present review, we aim to provide an extensive
      overview of the current clinical data and the prognostic value of different EMT
      markers that have been analysed in CCA. We summarize all the regulatory networks
      implicated in EMT from the membrane receptors to the main EMT-inducing
      transcription factors (SNAIL, TWIST and ZEB). Furthermore, since a tumor is a
      complex structure not exclusively formed by tumor cells, we also address the
      prominent role of the main cell types of the desmoplastic stroma that
      characterizes CCA in the regulation of EMT. Finally, we discuss the therapeutic
      considerations and difficulties faced to develop an effective anti-EMT treatment
      due to the redundancies and bypasses among the pathways regulating EMT.

PMID- 27686680
TI  - Effect of ventriculo-arterial coupling on transplant outcomes in cirrhotics:
      Analysis of pressure-volume curve relations.
AB  - BACKGROUND & AIMS: Ventriculo-arterial coupling (VAC) reflects the interaction
      between ventricular performance and effective arterial load. Current criteria for
      cirrhotic cardiomyopathy focus only on cardiac function without addressing the
      effect of hyperdynamic, low-resistance circulation. We investigated alterations
      in VAC in cirrhotic patients and their associations with post-liver transplant
      all-cause mortality. METHODS: In this single institution cohort study, cirrhotic
      patients who underwent liver transplantation (LT) (n=914) were retrospectively
      compared with healthy matched controls using noninvasively measured end-systolic
      ventricular elastance (Ees), arterial elastance (Ea), and VAC (Ea/Ees). All-cause
      mortality based on VAC values were investigated using a Cox hazard model with the
      inverse probability treatment weighting (IPTW) of propensity score. RESULTS:
      Cirrhotic patients had significantly lower Ees, Ea and VAC values than controls.
      Over a median of 30months, 96 patients died after LT. In patients with a high
      model for end-stage liver disease score (?25), VAC of >0.61 (highest tertile) had
      poorer survival outcomes than patients with VAC of ?0.50 (lowest tertile) (66.0%
      vs. 91.8%; Log-rank p=0.001), and was independently associated with risk of
      mortality (hazard ratio, 2.44; 95% CI, 1.10-5.39; p=0.028) compared with VAC of
      ?0.61 after IPTW adjustment. CONCLUSIONS: In cirrhotic patients, ventricular
      elastance and VAC values are lower than those in controls. However, in advanced
      cirrhotic patients, an increase in VAC value is associated with all-cause
      mortality after LT, suggesting that this non-invasive estimation of ventriculo
      arterial uncoupling is an additional novel prognosticator in cirrhotic
      cardiovascular disorders. LAY SUMMARY: In cirrhotic patients, cardiac dysfunction
      is latent and only manifests under stressful conditions because of arterial
      vasodilation. In this study, based on the pressure-volume curve of cardiac
      function, we investigated characteristics of the ventricular-arterial coupling in
      cirrhotic patients and further found that disparities in the ventriculo-arterial
      relationship are associated with graft failure and all-cause mortality after
      liver transplantation.

PMID- 27686681
TI  - Mimicking the Impact of Infant Tongue Peristalsis on Behavior of Solid Oral
      Dosage Forms Administered During Breastfeeding.
AB  - An in vitro simulation system was developed to study the effect of an infant's
      peristaltic tongue motion during breastfeeding on oral rapidly disintegrating
      tablets in the mouth, for use in rapid product candidate screening. These tablets
      are being designed for use inside a modified nipple shield worn by a mother
      during breastfeeding, a proposed novel platform technology to administer drugs
      and nutrients to breastfeeding infants. In this study, the release of a model
      compound, sulforhodamine B, from tablet formulations was studied under
      physiologically relevant forces induced by compression and rotation of a tongue
      mimic. The release profiles of the sulforhodamine B in flowing deionized water
      were found to be statistically different using 2-way ANOVA with matching, when
      tongue mimic rotation was introduced for 2 compression levels representing 2
      tongue strengths (p = 0.0013 and p < 0.0001 for the lower and higher compression
      settings, respectively). Compression level was found to be a significant factor
      for increasing model compound release at rotational rates representing
      nonnutritive breastfeeding (p = 0.0162). This novel apparatus is the first to
      simulate the motion and pressures applied by the tongue and could be used in
      future infant oral product development.

PMID- 27686682
TI  - Note on the Use of Diametrical Compression to Determine Tablet Tensile Strength.
AB  - The diametrical compression (DC) test, as defined in United States Pharmacopeia
      <1217> and in American Society for Testing and Materials testing standard D 3967,
      has been used extensively to derive the tensile strength (TS) of pharmaceutical
      tablets from the measured breaking force. DC-derived TSs provide a good approach
      to measuring the consistency of tablet mechanical properties from one batch to
      the next. For these quality control type applications, method precision is
      required, but accuracy is not. In addition, DC has been used to calibrate
      parameters of the Druker Prager Cap model, a yield criterion expressing the
      failure of a powder compact under arbitrary 3D loading conditions. For this
      application, the DC method must not only provide suitable precision but also
      provide accuracy. In this work, we explore the accuracy of the DC method by
      comparing TS results to those of the 3-point bend test method (also defined in
      United States Pharmacopeia <1217>). We conclude that the true TS of a powder
      compact is approximately double the DC-derived value. Although historical
      literature assumes that tablets fracture under tension along the centerline of
      the tablet, analysis of the stress state suggests that tablets are likely to
      fracture under shear. The impact of this ~50% error should be considered when
      accuracy of the TS result is required.

PMID- 27686683
TI  - Assessment of Tablet Surface Hardness by Laser Ablation and Its Correlation With
      the Erosion Tendency of Core Tablets.
AB  - Surface erosion of uncoated tablets results in processing problems such as
      dusting and defects during coating and is governed by the strength of particle
      bonding on tablet surface. In this study, the correlation between dusting
      tendency of tablets in a coating pan with friability and laser ablation surface
      hardness was assessed using tablets containing different concentrations of
      magnesium stearate and tartaric acid. Surface erosion propensity of different
      batches was evaluated by assessing their dusting tendency in the coating pan. In
      addition, all tablets were analyzed for crushing strength, friability, modified
      friability test using baffles in the friability apparatus, and weight loss after
      laser ablation. Tablets with similar crushing strength showed differences in
      their surface erosion and dusting tendency when rotated in a coating pan. These
      differences did not correlate well with tablet crushing strength or friability
      but did show reasonably good correlation with mass loss after laser ablation.
      These results suggest that tablet surface mass loss by laser ablation can be used
      as a minipiloting (small-scale) tool to assess tablet surface properties during
      early stages of drug product development to assess the risk of potential large
      scale manufacturing issues.

PMID- 27686685
TI  - Abstracts of the Meeting of October 10, 1998 of the Belgian Society of Internal
      Medicine.

PMID- 27686684
TI  - A case report of unusually long lag time between immunotactoid glomerulopathy
      (itg) diagnosis and diffuse large B-cell lymphoma (DLBCL) development.
AB  - BACKGROUND: Immunotactoid glomerulopathy (ITG) is a rare cause of proteinuria
      characterized by organized microtubular deposits in the glomerulus. ITG has been
      associated with underlying lymphoproliferative disorders and any renal impairment
      may be reversible with treatment of the concomitant hematologic malignancy. This
      case is the first reported in literature where diffuse large B cell lymphoma
      developed two years following the initial ITG diagnosis. CASE PRESENTATION: A 55
      year-old woman with a history of well-controlled diabetes mellitus and
      thalassemia trait presented with proteinuria (830 mg/day) in 2010. Initially, she
      was managed with renin-angiotensin-aldosterone-system blockade. In 2012, the
      proteinuria worsened (4.3 g/day) and a renal biopsy showed immunotactoid
      glomerulopathy (Fig. 1). Despite extensive work up, no lymphoproliferative
      disorder was initially found. In January 2014, the patient presented with a soft
      palate mass found on biopsy to be diffuse large B-cell lymphoma. She received 6
      cycles of R-CHOP, 4 cycles of high dose methotrexate chemotherapy for CNS
      prophylaxis and 30 Gy of Intensity Modulated Radiation Therapy. Follow-up
      revealed complete remission of diffuse large B-cell lymphoma and resolution of
      proteinuria from the ITG. CONCLUSION: As we recognize that patients with ITG may
      develop hematopoietic neoplasms, close long-term monitoring is important.
      Moreover, treatment of the lymphoproliferative disorder can allow for complete
      remission of ITG.

PMID- 27686687
TI  - Spectral characteristics of intracranial electroencephalographic activity in
      patients with Lennox-Gastaut syndrome.
AB  - OBJECTIVE: The purpose of the current study was to characterize the frequency
      profiles of epileptogenic regions, independent of visible epileptiform
      discharges, in intracranial EEG (iEEG) recordings of Lennox-Gastaut syndrome
      (LGS) patients. METHODS: We selected eight LGS patients who underwent resective
      surgery in the absence of definite neuroimaging findings. We calculated the
      absolute and relative band powers of continuous spike-free iEEG data and compared
      the characteristics of the resected and remaining regions. RESULTS: For absolute
      band powers, there was a trend for higher absolute gamma band power in the
      remaining brain section. We also found that the absolute delta power in the
      resected area was higher than that in the remaining area. However, this trend was
      not statistically different in all patients. For relative band powers, we found
      decreased relative band power in the beta and gamma band ranges within the areas
      defined by the surgical margins. Delta, theta, and alpha relative band power
      differences between the resected and remaining areas were inconsistent between
      the subjects. CONCLUSIONS: Our results showed systematic relative beta and gamma
      band power variation in the resected areas of LGS patients.

PMID- 27686688
TI  - A pediatric patient of hemorrhagic acute transverse myelitis.
AB  - An 11-year-old boy presented with progressive leg hypesthesia but no history of
      trauma. Dysuria and constipation appeared subsequent to gait difficulty. He was
      admitted 8days after onset. Spinal magnetic resonance imaging (MRI) revealed
      longitudinal hyperintensity with cord swelling and hypointensity on T2-weighted
      images, suggesting severe inflammation and microbleeding change, respectively.
      Gadolinium contrast-enhanced MRI demonstrated mild enhancement in the lesions.
      Platelet count and coagulation findings were normal, and cerebrospinal fluid
      analysis showed no pleocytosis. He was diagnosed with idiopathic acute transverse
      myelitis (ATM), and intravenous methylprednisolone pulse therapy and
      plasmapheresis were initiated. On day 14, motor dysfunction aggravated suddenly,
      accompanied by expanding hemorrhagic lesions. Thereafter, administration of
      intravenous immunoglobulin, repeated intravenous methylprednisolone pulse therapy
      and prednisolone for one month resulted in complete recovery four months later.
      Both anti-aquaporin-4 and anti-myelin oligodendrocyte glycoprotein antibodies
      were negative. We presented the first pediatric case showing hemorrhagic spinal
      lesions in the clinical course of ATM. This severe complication should be
      recognized in the management of ATM.

PMID- 27686689
TI  - An Evaluation of Treatment Patterns and Outcomes in Elderly Patients Newly
      Diagnosed With Acute Myeloid Leukemia: A Retrospective Analysis of Electronic
      Medical Records From US Community Oncology Practices.
AB  - BACKGROUND: Many elderly patients with acute myeloid leukemia (AML) are
      considered ineligible for standard intensive induction therapy due to performance
      status and comorbidities. We analyzed treatment patterns and outcomes among
      elderly patients newly diagnosed with AML in the US community oncology setting.
      METHODS: A retrospective observational study was conducted using patient-level
      data from a network of US community oncology practices provided by Altos
      Solutions. Patients aged >= 60 years, diagnosed with AML between November 2005
      and February 2014, with >= 1 recorded visit and >= 6 months between diagnosis and
      data cutoff, were included. Only patients who received active treatment or best
      supportive care (BSC) per National Comprehensive Cancer Network (NCCN) AML
      Guidelines were analyzed. RESULTS: Of 1139 patients meeting the inclusion
      criteria, 922 (median age 76 years) received NCCN-recommended treatments:
      standard induction (n = 5), low-intensity therapy (n = 425), BSC with hydroxyurea
      (HU) (n = 36), or BSC without HU (n = 455). For the low-intensity therapy cohort,
      median time from diagnosis to treatment initiation was 17 days; median duration
      of therapy was 5.1 months. Median overall survival (OS) from diagnosis in the low
      intensity, BSC with HU, and BSC without HU groups was 12.3, 7.0, and 49.4 months,
      respectively. Median time to next therapy/death was 10.1 months in patients
      receiving low-intensity therapy. A higher proportion of patients receiving low
      intensity therapy required transfusion or other supportive care versus those
      receiving BSC. CONCLUSIONS: As expected, OS in patients receiving low-intensity
      therapy or BSC with HU is poor for elderly patients with AML. Remarkably,
      intensive induction strategies are rarely used for older patients in community
      oncology practice.

PMID- 27686690
TI  - Glutathione S-Transferase T1 (GSTT1) Null Polymorphism, Smoking, and Their
      Interaction in Coronary Heart Disease: A Comprehensive Meta-Analysis.
AB  - BACKGROUND: The association between glutathione S-transferase T1 (GSTT1) null
      polymorphism and coronary heart disease (CHD) is inconsistent among studies, and
      data on the GSTT1 null genotype-smoking interplay in CHD is lacking. We conducted
      this meta-analysis to investigate the relationship between GSTT1 null
      polymorphism and CHD and to assess the potential interaction between GSTT1 null
      genotype and smoking. METHODS: PubMed and EMBASE databases were searched up to 27
      January 2016 using the appropriate terms. Odds ratios were pooled using either
      fixed-effects or random-effects models. RESULTS: Twenty-nine articles including
      31 studies with 15,004 cases and 35,597 controls were eligible. The random
      effects model showed that the GSTT1 null genotype was associated with increased
      CHD risk (OR=1.213, 95%CI: 1.004-1.467; I2=90.4%). After excluding 10 studies
      detected by Galbraith plot, the fixed effects summary estimate also showed an
      increased risk of CHD (OR=1.14, 95% CI: 1.06-1.22; I2=27.7%). A case-only
      analysis including eight studies showed a statistically significant positive
      interaction between GSTT1 null polymorphism and smoking status on CHD (OR=1.34,
      95% CI: 1.09-1.64; I2=0%). Sensitivity analyses further supported the
      associations. No publication bias was observed. CONCLUSIONS: This meta-analysis
      suggests that GSTT1 null polymorphism is associated with the risk of CHD. To our
      knowledge, this is the first meta-analysis to prove a positive effect of the
      interaction between GSTT1 null genotype and smoking status on the risk of CHD.
      Future studies with detailed individual information are needed to confirm our
      findings.

PMID- 27686691
TI  - Functional Effects of Bulbospongiosus Muscle Sparing on Ejaculatory Function and
      Post-Void Dribbling after Bulbar Urethroplasty.
AB  - PURPOSE: Bulbar urethroplasty outcomes studies have shown low but significant
      rates of post-void dribbling and ejaculatory dysfunction. The bulbospongiosus
      muscle is involved with the expulsion of seminal fluid and urine from the bulbar
      urethra and, thus, we hypothesized that performing urethroplasty using a
      technique that does not split the muscle may result in better postoperative
      patient reported ejaculatory function and less post-void dribbling. MATERIALS AND
      METHODS: We performed a multi-institutional matched, case-control analysis
      comparing men treated with a bulbospongiosus sparing technique to men treated
      with the traditional nonbulbospongiosus sparing technique. Preoperative and
      postoperative (3 to 12 months) ejaculatory function was assessed using the 4
      ejaculatory questions of the Male Sexual Health Questionnaire short form as well
      as a patient perception questionnaire. Post-void dribbling was assessed using a
      validated urethroplasty questionnaire. RESULTS: A total of 25 patients who
      underwent bulbospongiosus sparing urethroplasty and 25 who underwent
      nonbulbospongiosus sparing urethroplasty were matched by total preoperative Male
      Sexual Health Questionnaire score, age, and performance of excision and primary
      anastomosis. The bulbospongiosus sparing and nonbulbospongiosus sparing groups
      had similar postoperative total Male Sexual Health Questionnaire scores (15.24 vs
      15.40, respectively, p=0.90) and there were no significant postoperative
      questionnaire score changes in either group (bulbospongiosus sparing 14.56 to
      15.24, p=0.4; nonbulbospongiosus sparing 14.64 vs 15.40, p=0.44). Individual
      responses to the Male Sexual Health Questionnaire were analyzed and no
      statistically significant difference was found between the groups. Rates of
      postoperative post-void dribbling and perception of ejaculatory function were
      similar between the groups. CONCLUSIONS: Sparing the bulbospongiosus muscle
      during urethroplasty does not seem to have a significant impact on patient
      reported ejaculatory function or post-void dribbling compared with
      nonbulbospongiosus sparing urethroplasty at early followup.

PMID- 27686692
TI  - Metabolic syndrome in breast cancer survivors with high carbohydrate consumption:
      The first report in community setting.
AB  - BACKGROUND & AIMS: This study was conducted to examine the prevalence of and
      lifestyle factors associated with the metabolic syndrome in breast cancer
      survivors and to compare those factors with controls without cancer in a
      community setting. METHODS: This study included 584 female breast cancer
      survivors >=3 years after the initial diagnosis and 2336 age-matched cancer-free
      female controls from 39 community health examination centers located in 14 urban
      areas in Korea. The prevalence of the metabolic syndrome is shown. Factors
      associated with the metabolic syndrome were analyzed as odds ratios (ORs) in
      cancer survivors and controls; differences between the two groups in the ORs of
      associated factors were evaluated by calculating p-heterogeneity values. RESULTS:
      The prevalence of metabolic syndrome in breast cancer survivors and age-matched
      controls were 26.8% and 26.9%, respectively. Higher percentage of caloric intake
      from carbohydrates was associated with increased metabolic syndrome only in the
      breast cancer survivors (OR for the highest vs. lowest quartile for survivors =
      2.48 [95% CI = 1.20-5.14]; OR for controls = 1.11 [95% CI = 0.81-1.51]; P
      heterogeneity = 0.046). Sweat-inducing exercise for >=150 min/week was associated
      with a lower risk of metabolic syndrome only in controls (controls: OR = 0.72
      [95% CI = 0.58-0.89]; survivors: OR = 0.88 [95% CI = 0.57-1.36]). Older age,
      higher body mass index, and a lower education level (<=12 years) was associated
      with an increased prevalence of metabolic syndrome in both groups. CONCLUSIONS:
      Our results suggest that, in regions with excess carbohydrate intake, the
      association of the metabolic syndrome with percentage of caloric intake from
      carbohydrate might be more prominent than exercise in breast cancer survivors,
      compared with general population.

PMID- 27686693
TI  - Carbohydrates and insulin resistance in clinical nutrition: Recommendations from
      the ESPEN expert group.
AB  - Growing evidence underscores the important role of glycemic control in health and
      recovery from illness. Carbohydrate ingestion in the diet or administration in
      nutritional support is mandatory, but carbohydrate intake can adversely affect
      major body organs and tissues if resulting plasma glucose becomes too high, too
      low, or highly variable. Plasma glucose control is especially important for
      patients with conditions such as diabetes or metabolic stress resulting from
      critical illness or surgery. These patients are particularly in need of glycemic
      management to help lessen glycemic variability and its negative health
      consequences when nutritional support is administered. Here we report on recent
      findings and emerging trends in the field based on an ESPEN workshop held in
      Venice, Italy, 8-9 November 2015. Evidence was discussed on pathophysiology,
      clinical impact, and nutritional recommendations for carbohydrate utilization and
      management in nutritional support. The main conclusions were: a) excess glucose
      and fructose availability may exacerbate metabolic complications in skeletal
      muscle, adipose tissue, and liver and can result in negative clinical impact; b)
      low-glycemic index and high-fiber diets, including specialty products for
      nutritional support, may provide metabolic and clinical benefits in individuals
      with obesity, insulin resistance, and diabetes; c) in acute conditions such as
      surgery and critical illness, insulin resistance and elevated circulating glucose
      levels have a negative impact on patient outcomes and should be prevented through
      nutritional and/or pharmacological intervention. In such acute settings, efforts
      should be implemented towards defining optimal plasma glucose targets, avoiding
      excessive plasma glucose variability, and optimizing glucose control relative to
      nutritional support.

PMID- 27686694
TI  - Current interventional strategy for the treatment of hepatic alveolar
      echinococcosis.
AB  - INTRODUCTION: The use of various types of invasive interventions combined with
      anti-infective drugs in the therapeutic strategy of alveolar echinococcosis (AE)
      has changed during the last 30 years. Areas covered: This article reviews the
      current respective indications of surgical, percutaneous and perendoscopic
      interventions in AE and proposes an integrative therapeutic strategy. Expert
      commentary: Hepatic resection is indicated whenever it is feasible and curative;
      palliative surgery should be avoided; percutaneous procedures are best adapted to
      the drainage of the necrotic cavity present in advanced cases; perendoscopic
      procedures with stenting are best adapted to alleviating the biliary
      complications that are common and life-threatening in AE patients. Continuous
      administration of albendazole or mebendazole, without interruption is mandatory
      in all cases, temporarily (recommended duration: 2 years) after radical lesion
      resection in patients without immune suppression; for life in all other cases.
      Long-term follow-up is essential.

PMID- 27686695
TI  - Selecting symptom instruments for cardiovascular populations.
AB  - The purpose of this review is to provide a guide for researchers and clinicians
      in selecting an instrument to measure four commonly occurring symptoms (dyspnea,
      chest pain, palpitations, and fatigue) in cardiac populations (acute coronary
      syndrome, heart failure, arrhythmia/atrial fibrillation, and angina, or patients
      undergoing cardiac interventions). An integrative review of the literature was
      conducted. A total of 102 studies summarizing information on 36 different
      instruments are reported in this integrative review. The majority of the
      instruments measured multiple symptoms and were used for one population. A
      majority of the symptom measures were disease-specific and were multi
      dimensional. This review summarizes the psychometrics and defining
      characteristics of instruments to measure the four commonly occurring symptoms in
      cardiac populations. Simple, psychometrically strong instruments do exist and
      should be considered for use; however, there is less evidence of responsiveness
      to change over time for the majority of instruments.

PMID- 27686696
TI  - Development of a methodology for in vivo follow-up of hepatocellular carcinoma in
      hepatocyte specific Trim24-null mice treated with myo-inositol trispyrophosphate.
AB  - BACKGROUND: Genetically induced hepatocellular carcinoma (HCC) models are
      generally used to investigate carcinogenesis pathways, but very few attempts were
      made to valorize them for pharmacological testing. This study describes a micro
      computed tomography (micro-CT) - based methodology for the diagnostic and
      lifelong follow-up of HCC in the hepatocyte-specific Trim24-null mouse line. Myo
      inositol trispyrophosphate (ITPP) was tested as anti-cancer drug. METHODS:
      Partial hepatectomy was performed in 2 months-old Trim24-null mice, in order to
      accelerate the carcinogenesis process. HCC diagnosis was obtained by micro-CT
      scan with double contrast agent: 10 MUl/g FenestraTM LC was injected
      intraperitoneally 6 h prior to imaging and 10 MUl/g FenestraTM VC was injected
      intravenously 15 min prior to imaging. Twenty three hepatocyte-specific Trim24
      null mice were considered for ITPP testing (3 mg/g/week intraperitoneally during
      10 months in 12 mice, versus 11 controls). Lifelong follow-up was performed using
      micro-CT. Comparative analysis was performed using unpaired t test with Welch
      correction and survival curves were compared by log-rank test. Gene expression
      analysis was performed using the RT q-PCR technique. RESULTS: Double contrast
      micro-CT scan allowed HCC diagnosis as hypodense, isodense or hyperdense nodules.
      Positive predictive value was 81.3 %. Negative predictive value was 83.3 %. Tumor
      growth could be objectified by micro-CT scan before the ITPP treatment was
      started, and at 3 and 9 months follow-up. Significant progression of tumor volume
      was demonstrated in the both groups, with no difference between groups (p >
      0.05). In the ITPP group, a mild decrease in tumor doubling time was first
      observed (31.9 +/- 12 days, p > 0.05) followed by a significant increase (59.8 +/
      18.3 days, p = 0.008). However, tumor doubling time was not different between
      groups (p > 0.05). Median survival after treatment initiation was 223 days
      (controls) versus 296 days (ITPP group, p = 0.0027). HIF1alpha, VEGF, glutamine
      synthase, osteopontin expression levels were not significantly modified at the
      end of follow-up. In the ITPP group, the p53 expression profile was inversed as
      compared to the control group, higher in non-tumor livers than in tumors.
      CONCLUSION: ITPP treatment allowed for a two-month survival improvement, with
      better tolerance of tumor burden and apoptosis increase in non-tumor,
      pathological livers.

PMID- 27686697
TI  - Patient Discussion About Sexual Health With Health Care Providers After Cancer-A
      National Survey.
AB  - INTRODUCTION: A discussion about sexuality should become a routine part of the
      personalized care pathway for patients with cancer. AIM: To assess rates of
      patient discussion about sexuality with health care providers after cancer.
      METHODS: We used data from the representative French nationwide 2012 VICAN
      survey, which included 4,349 adults 18 to 82 years old who were still alive 2
      years after diagnosis at 12 cancer sites. MAIN OUTCOME MEASURES: Self-reported
      rates of discussion about sexuality with health care providers were assessed, and
      associated factors were tested after systematic adjustment for a sexual health
      indicator (created from six items of the Relationship and Sexuality Scale).
      RESULTS: Of 4,181 respondents to the question on a discussion about sexuality,
      54.7% reported that nobody had proposed a discussion to them, 21.9% did not want
      any discussion, and 23.4% had had a discussion. Women had less discussion about
      sexuality with health care providers (11.1% vs 36.7% of men, P < .001) and were
      more likely to request a discussion at their own initiative (62.9% vs 48.0% of
      men, P < .001). Discussion about sexuality was more frequent with patients with
      prostate (56.3%) and cervical (39.6%) cancer, but increasing age was associated
      with a greater reluctance to discuss this issue (odds ratio = 1.17, 95% CI = 1.04
      1.2). The likelihood of discussion increased with severe sexual problems,
      radiotherapy, general sequelae, having an information-seeker profile, previous
      professional psychological help, and initial treatment in private centers.
      Patients initially wishing for psychological help were more likely to desire a
      discussion about sexuality. CONCLUSION: Sexuality receives little attention in
      French patients with cancer. Inequalities in the discussion about sexuality were
      observed in relation to the type of care center where the patient was initially
      managed. Information on supportive interventions, including more systematic
      referral for professional psychological help, should be developed to facilitate
      discussion and should be offered to all patients, irrespective of severity of
      sexual problems, age, sex, cancer site, and care center.

PMID- 27686698
TI  - Characterization of EEG patterns in brain-injured subjects and controls after a
      Snoezelen((r)) intervention.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to assess the changes induced
      in electroencephalographic (EEG) activity by a Snoezelen((r)) intervention on
      individuals with brain-injury and control subjects. METHODS: EEG activity was
      recorded preceding and following a Snoezelen((r)) session in 18 people with
      cerebral palsy (CP), 18 subjects who have sustained traumatic brain-injury (TBI)
      and 18 controls. EEG data were analyzed by means of spectral and nonlinear
      measures: median frequency (MF), individual alpha frequency (IAF), sample entropy
      (SampEn) and Lempel-Ziv complexity (LZC). RESULTS: Our results showed decreased
      values for MF, IAF, SampEn and LZC as a consequence of the therapy. The main
      changes between pre-stimulation and post-stimulation conditions were found in
      occipital and parietal brain areas. Additionally, these changes are more
      widespread in controls than in brain-injured subjects, which can be due to
      cognitive deficits in TBI and CP groups. CONCLUSIONS: Our findings support the
      notion that Snoezelen((r)) therapy affects central nervous system, inducing a
      slowing of oscillatory activity, as well as a decrease of EEG complexity and
      irregularity. These alterations seem to be related with higher levels of
      relaxation of the participants.

PMID- 27686699
TI  - Supervised discretization can discover risk groups in cancer survival analysis.
AB  - Discretization of continuous variables is a common practice in medical research
      to identify risk patient groups. This work compares the performance of gold
      standard categorization procedures (TNM+A protocol) with that of three supervised
      discretization methods from Machine Learning (CAIM, ChiM and DTree) in the
      stratification of patients with breast cancer. The performance for the
      discretization algorithms was evaluated based on the results obtained after
      applying standard survival analysis procedures such as Kaplan-Meier curves, Cox
      regression and predictive modelling. The results show that the application of
      alternative discretization algorithms could lead the clinicians to get valuable
      information for the diagnosis and outcome of the disease. Patient data were
      collected from the Medical Oncology Service of the Hospital Clinico Universitario
      (Malaga, Spain) considering a follow up period from 1982 to 2008. 

PMID- 27686700
TI  - Study of heat transfer on physiological driven movement with CNT nanofluids and
      variable viscosity.
AB  - BACKGROUND AND OBJECTIVES: With ongoing interest in CNT nanofluids and materials
      in biotechnology, energy and environment, microelectronics, composite materials
      etc., the current investigation is carried out to analyze the effects of variable
      viscosity and thermal conductivity of CNT nanofluids flow driven by cilia induced
      movement through a circular cylindrical tube. Metachronal wave is generated by
      the beating of cilia and mathematically modeled as elliptical wave propagation by
      Blake (1971). METHODS, RESULTS AND CONCLUSIONS: The problem is formulated in the
      form of nonlinear partial differential equations, which are simplified by using
      the dimensional analysis to avoid the complicacy of dimensional homogeneity.
      Lubrication theory is employed to linearize the governing equations and it is
      also physically appropriate for cilia movement. Analytical solutions for
      velocity, temperature and pressure gradient and stream function are obtained. The
      analytical results are numerically simulated by using the Mathematica Software
      and plotted the graphs for velocity profile, temperature profile, pressure
      gradient and stream lines for better discussion and visualization. This model is
      applicable in physiological transport phenomena to explore the nanotechnology in
      engineering the artificial cilia and ciliated tube/pipe.

PMID- 27686701
TI  - GPU accelerated dynamic respiratory motion model correction for MRI-guided
      cardiac interventions.
AB  - BACKGROUND AND OBJECTIVES: The use of pre-procedural magnetic resonance (MR)
      roadmap images for interventional guidance has limited anatomical accuracy due to
      intra-procedural respiratory motion of the heart. Therefore, the objective of
      this study is to explore the use of a rapidly updated dynamic motion model to
      correct for respiratory motion induced errors during MRI-guided cardiac
      interventions. The motivation for the proposed technique is to improve the
      accuracy of MRI guidance by taking advantage of the anatomical context provided
      by the high resolution prior images and the respiratory motion information
      present in a series of realtime MR images. METHODS: We implemented a GPU
      accelerated image registration algorithm to derive the respiratory motion
      information and used the resulting transformation parameters to update an
      adaptive motion model once every heart cycle. In the subsequent heart cycle, the
      dynamic motion model could be used to predict the respiratory motion and provide
      a motion estimate to realign the prior volume with the realtime MR image. This
      iterative update and prediction process is then continuously repeated. RESULTS:
      The GPU accelerated image registration algorithm could be completed in an average
      of 176.9 +/- 14.0 ms, which is 139* faster than a CPU implementation. Thus, it
      was feasible to update the dynamic model once every heart cycle. The proposed
      dynamic model was also able to improve the registration accuracy from 86.0 +/-
      7.5% to 93.0 +/- 3.3% in case of variable breathing patterns, as evaluated by the
      dice similarity coefficient of the left ventricular border overlap between the
      prior and realtime images. CONCLUSIONS: The feasibility of a dynamic motion
      correction framework was demonstrated. The resulting improvements may lead to
      more accurate MRI-guided cardiac interventions in the future.

PMID- 27686702
TI  - Predicting intentions of nurses to adopt patient personal health records: A
      structural equation modeling approach.
AB  - OBJECTIVE: The American Nurses Association endorsed the use of online patient
      personal health records (PHRs) and challenged all nurses to obtain the health
      records of patients. However, few studies have explored the factors associated
      with the intentions of nurses to use patient PHRs. Our study used an extended
      technology acceptance model, with the theory of planned behavior and perceived
      credibility, to explore factors associated with the intentions of nurses to use
      patient PHRs. METHODS: This cross-sectional quantitative study comprised a sample
      of 635 nurses who had worked full time for at least 3 months, and they were
      recruited from three hospitals affiliated with a university in northern Taiwan.
      We used a questionnaire to obtain information on perceived usefulness, perceived
      ease of use, perceived credibility, subjective norms, computer self-efficacy,
      attitudes, and intentions to use patient PHRs. RESULTS: This study indicated that
      perceived usefulness, computer self-efficacy, and subjective norms significantly
      and positively affected intentions to use patient PHRs. The attitudes of nurses
      toward PHR adoption directly influenced their intentions to use patient PHRs.
      Moreover, subjective norms indirectly affected intentions to use patient PHRs
      through the factor of attitudes. The proposed model explained 82.1% of the
      variance in the intentions of nurses to use patient PHRs. CONCLUSIONS: Subjective
      norms had stronger total effects on the attitudes and intentions of nurses to use
      patient PHRs than perceived usefulness, perceived ease of use, or perceived
      credibility did. The results may help practitioners further understand that the
      attitudes of nurses toward using patient PHRs are influenced by peer groups and
      administrators. The current study provides evidence that peer groups influence
      the attitudes of nurses to use patient PHRs, which in turn influence their
      intentions toward PHR adoption.

PMID- 27686703
TI  - Traumatic brain injury in pedestrian-vehicle collisions: Convexity and
      suitability of some functionals used as injury metrics.
AB  - BACKGROUND AND OBJECTIVE: Abrupt accelerations or decelerations can cause large
      strain in brain tissues and, consequently, different forms of Traumatic Brain
      Injury (TBI). In order to predict the effect of the accelerations on the soft
      tissues of the brain, many different injury metrics have been proposed
      (typically, an injury metric is a real valued functional of the accelerations).
      The objective of this article is to make a formal and empirical comparison, in
      order to identify general criteria for reasonable injury metrics, and propose a
      general guideline to avoid ill-proposed injury metrics. METHODS: A medium-sized
      sample of vehicle-pedestrian collisions, from Post Mortem Human Subject (PMHS)
      tests, is analyzed. A statistical study has been conducted in order to determine
      the discriminant power of the usual metrics. We use Principal Component Analysis
      to reduce dimensionality and to check consistency among the different metrics. In
      addition, this article compares the mathematical properties of some of these
      functionals, trying to identify the desirable properties that any of those
      functionals needs to fulfill in order to be useful for optimization. RESULTS: We
      have found a pair-wise consistency of all the currently used metrics (any two
      injury metrics are always positively related). In addition, we observed that two
      independent principal factors explain about 72.5% of the observed variance among
      all collision tests. This is remarkable because it indicates that despite high
      number of different injury metrics, a reduced number of variables can explain the
      results of all these metrics. With regard to the formal properties, we found that
      essentially all injury mechanisms can be accounted by means of scalable,
      differentiable and convex functionals (we propose to call minimization suitable
      injury metric any metric having these three formal properties). In addition three
      useful functionals, usable as injury metrics, are identified on the basis of the
      empirical comparisons. CONCLUSIONS: The commonly used metrics are highly
      consistent, but also highly redundant. Formal minimal conditions of a reasonable
      injury metric has been identified. Future proposals of injury metrics can benefit
      from the results of this study.

PMID- 27686704
TI  - Automatic identification of epileptic seizures from EEG signals using linear
      programming boosting.
AB  - BACKGROUND AND OBJECTIVE: Computerized epileptic seizure detection is essential
      for expediting epilepsy diagnosis and research and for assisting medical
      professionals. Moreover, the implementation of an epilepsy monitoring device that
      has low power and is portable requires a reliable and successful seizure
      detection scheme. In this work, the problem of automated epilepsy seizure
      detection using singe-channel EEG signals has been addressed. METHODS: At first,
      segments of EEG signals are decomposed using a newly proposed signal processing
      scheme, namely complete ensemble empirical mode decomposition with adaptive noise
      (CEEMDAN). Six spectral moments are extracted from the CEEMDAN mode functions and
      train and test matrices are formed afterward. These matrices are fed into the
      classifier to identify epileptic seizures from EEG signal segments. In this work,
      we implement an ensemble learning based machine learning algorithm, namely linear
      programming boosting (LPBoost) to perform classification. RESULTS: The efficacy
      of spectral features in the CEEMDAN domain is validated by graphical and
      statistical analyses. The performance of CEEMDAN is compared to those of its
      predecessors to further inspect its suitability. The effectiveness and the
      appropriateness of LPBoost are demonstrated as opposed to the commonly used
      classification models. Resubstitution and 10 fold cross-validation error analyses
      confirm the superior algorithm performance of the proposed scheme. The
      algorithmic performance of our epilepsy seizure identification scheme is also
      evaluated against state-of-the-art works in the literature. Experimental outcomes
      manifest that the proposed seizure detection scheme performs better than the
      existing works in terms of accuracy, sensitivity, specificity, and Cohen's Kappa
      coefficient. CONCLUSION: It can be anticipated that owing to its use of only one
      channel of EEG signal, the proposed method will be suitable for device
      implementation, eliminate the onus of clinicians for analyzing a large bulk of
      data manually, and expedite epilepsy diagnosis.

PMID- 27686705
TI  - A new computer vision-based approach to aid the diagnosis of Parkinson's disease.
AB  - BACKGROUND AND OBJECTIVE: Even today, pointing out an exam that can diagnose a
      patient with Parkinson's disease (PD) accurately enough is not an easy task.
      Although a number of techniques have been used in search for a more precise
      method, detecting such illness and measuring its level of severity early enough
      to postpone its side effects are not straightforward. In this work, after
      reviewing a considerable number of works, we conclude that only a few techniques
      address the problem of PD recognition by means of micrography using computer
      vision techniques. Therefore, we consider the problem of aiding automatic PD
      diagnosis by means of spirals and meanders filled out in forms, which are then
      compared with the template for feature extraction. METHODS: In our work, both the
      template and the drawings are identified and separated automatically using image
      processing techniques, thus needing no user intervention. Since we have no
      registered images, the idea is to obtain a suitable representation of both
      template and drawings using the very same approach for all images in a fast and
      accurate approach. RESULTS: The results have shown that we can obtain very
      reasonable recognition rates (around ~67%), with the most accurate class being
      the one represented by the patients, which outnumbered the control individuals in
      the proposed dataset. CONCLUSIONS: The proposed approach seemed to be suitable
      for aiding in automatic PD diagnosis by means of computer vision and machine
      learning techniques. Also, meander images play an important role, leading to
      higher accuracies than spiral images. We also observed that the main problem in
      detecting PD is the patients in the early stages, who can draw near-perfect
      objects, which are very similar to the ones made by control patients.

PMID- 27686706
TI  - Intraoral radiographs texture analysis for dental implant planning.
AB  - BACKGROUND AND OBJECTIVES: Computer vision extracts features or attributes from
      images improving diagnosis accuracy and aiding in clinical decisions. This study
      aims to investigate the feasibility of using texture analysis of periapical
      radiograph images as a tool for dental implant treatment planning. METHODS:
      Periapical radiograph images of 127 jawbone sites were obtained before and after
      implant placement. From the superimposition of the pre- and post-implant images,
      four regions of interest (ROI) were delineated on the pre-implant images for each
      implant site: mesial, distal and apical peri-implant areas and a central area.
      Each ROI was analysed using Matlab(r) software and seven image attributes were
      extracted: mean grey level (MGL), standard deviation of grey levels (SDGL),
      coefficient of variation (CV), entropy (En), contrast, correlation (Cor) and
      angular second moment (ASM). Images were grouped by bone types-Lekholm and Zarb
      classification (1,2,3,4). Peak insertion torque (PIT) and resonance frequency
      analysis (RFA) were recorded during implant placement. Differences among groups
      were tested for each image attribute. Agreement between measurements of the peri
      implant ROIs and overall ROI (peri-implant + central area) was tested, as well as
      the association between primary stability measures (PIT and RFA) and texture
      attributes. RESULTS: Differences among bone type groups were found for MGL (p =
      0.035), SDGL (p = 0.024), CV (p < 0.001) and En (p < 0.001). The apical ROI
      showed a significant difference from the other regions for all attributes, except
      Cor. Concordance correlation coefficients were all almost perfect (rho > 0.93),
      except for ASM (rho = 0.62). Texture attributes were significantly associated
      with the implant stability measures. CONCLUSION: Texture analysis of periapical
      radiographs may be a reliable non-invasive quantitative method for the assessment
      of jawbone and prediction of implant stability, with potential clinical
      applications.

PMID- 27686707
TI  - Correlation coefficient based supervised locally linear embedding for pulmonary
      nodule recognition.
AB  - BACKGROUND AND OBJECTIVE: Dimensionality reduction techniques are developed to
      suppress the negative effects of high dimensional feature space of lung CT images
      on classification performance in computer aided detection (CAD) systems for
      pulmonary nodule detection. METHODS: An improved supervised locally linear
      embedding (SLLE) algorithm is proposed based on the concept of correlation
      coefficient. The Spearman's rank correlation coefficient is introduced to adjust
      the distance metric in the SLLE algorithm to ensure that more suitable
      neighborhood points could be identified, and thus to enhance the discriminating
      power of embedded data. The proposed Spearman's rank correlation coefficient
      based SLLE (SC(2)SLLE) is implemented and validated in our pilot CAD system using
      a clinical dataset collected from the publicly available lung image database
      consortium and image database resource initiative (LICD-IDRI). Particularly, a
      representative CAD system for solitary pulmonary nodule detection is designed and
      implemented. After a sequential medical image processing steps, 64 nodules and
      140 non-nodules are extracted, and 34 representative features are calculated. The
      SC(2)SLLE, as well as SLLE and LLE algorithm, are applied to reduce the
      dimensionality. Several quantitative measurements are also used to evaluate and
      compare the performances. RESULTS: Using a 5-fold cross-validation methodology,
      the proposed algorithm achieves 87.65% accuracy, 79.23% sensitivity, 91.43%
      specificity, and 8.57% false positive rate, on average. Experimental results
      indicate that the proposed algorithm outperforms the original locally linear
      embedding and SLLE coupled with the support vector machine (SVM) classifier.
      CONCLUSIONS: Based on the preliminary results from a limited number of nodules in
      our dataset, this study demonstrates the great potential to improve the
      performance of a CAD system for nodule detection using the proposed SC(2)SLLE.

PMID- 27686708
TI  - Integrating evolutionary game theory into an agent-based model of ductal
      carcinoma in situ: Role of gap junctions in cancer progression.
AB  - BACKGROUND AND OBJECTIVE: There are many cells with various phenotypic behaviors
      in cancer interacting with each other. For example, an apoptotic cell may induce
      apoptosis in adjacent cells. A living cell can also protect cells from undergoing
      apoptosis and necrosis. These survival and death signals are propagated through
      interaction pathways between adjacent cells called gap junctions. The function of
      these signals depends on the cellular context of the cell receiving them. For
      instance, a receiver cell experiencing a low level of oxygen may interpret a
      received survival signal as an apoptosis signal. In this study, we examine the
      effect of these signals on tumor growth. METHODS: We make an evolutionary game
      theory component in order to model the signal propagation through gap junctions.
      The game payoffs are defined as a function of cellular context. Then, the game
      theory component is integrated into an agent-based model of tumor growth. After
      that, the integrated model is applied to ductal carcinoma in situ, a type of
      early stage breast cancer. Different scenarios are explored to observe the impact
      of the gap junction communication and parameters of the game theory component on
      cancer progression. We compare these scenarios by using the Wilcoxon signed-rank
      test. RESULTS: The Wilcoxon signed-rank test succeeds in proving a significant
      difference between the tumor growth of the model before and after considering the
      gap junction communication. The Wilcoxon signed-rank test also proves that the
      tumor growth significantly depends on the oxygen threshold of turning survival
      signals into apoptosis. CONCLUSIONS: In this study, the gap junction
      communication is modeled by using evolutionary game theory to illustrate its role
      at early stage cancers such as ductal carcinoma in situ. This work indicates that
      the gap junction communication and the oxygen threshold of turning survival
      signals into apoptosis can notably affect cancer progression.

PMID- 27686709
TI  - Improving the text classification using clustering and a novel HMM to reduce the
      dimensionality.
AB  - In text classification problems, the representation of a document has a strong
      impact on the performance of learning systems. The high dimensionality of the
      classical structured representations can lead to burdensome computations due to
      the great size of real-world data. Consequently, there is a need for reducing the
      quantity of handled information to improve the classification process. In this
      paper, we propose a method to reduce the dimensionality of a classical text
      representation based on a clustering technique to group documents, and a
      previously developed Hidden Markov Model to represent them. We have applied tests
      with the k-NN and SVM classifiers on the OHSUMED and TREC benchmark text corpora
      using the proposed dimensionality reduction technique. The experimental results
      obtained are very satisfactory compared to commonly used techniques like InfoGain
      and the statistical tests performed demonstrate the suitability of the proposed
      technique for the preprocessing step in a text classification task. 

PMID- 27686710
TI  - Profiling intra-patient type I diabetes behaviors.
AB  - BACKGROUND: The large intra-patient variability in type 1 diabetic patients
      dramatically reduces the ability to achieve adequate blood glucose control. A
      novel methodology to identify different blood glucose dynamics profiles will
      allow therapies to be more accurate and tailored according to patient's
      conditions and to the situations faced by patients (exercise, week-ends,
      holidays, menstruation, etc). MATERIALS AND METHODS: A clustering methodology
      based on the normalized compression distance is applied to identify different
      profiles for diabetic patients. First, the methodology is validated using "in
      silico" data from 10 patients in 3 different scenarios: days without exercise,
      poor controlled exercise days and days with well-controlled exercise. Second, we
      perform a series of in vivo experiments using data from 10 patients assessing the
      ability of the proposed methodology in real scenarios. RESULTS: In silico
      experiments show that the methodology is able to identify poor and well
      controlled days in theoretical scenarios. In vivo experiments present meaningful
      profiles for working days, bank days and other situations, where different
      insulin requirements were detected. CONCLUSIONS: A tool for profiling blood
      glucose dynamics of patients can be implemented in a short term to enhance
      existing analysis platforms using combined CGM-CSII systems. Besides coping with
      the information overload, the tool will assist physicians to adjust and improve
      insulin therapy and patients in the self-management of the disease.

PMID- 27686711
TI  - Dynamic ECG features for atrial fibrillation recognition.
AB  - BACKGROUND: Atrial fibrillation (AF) can cause the formation of blood clots in
      the heart. The clots may move to the brain and cause a stroke. Therefore, this
      study analyzed the ECG features of AF and normal sinus rhythm signals for AF
      recognition which were extracted by using a second-order dynamic system (SODS)
      concept. OBJECTIVE: To find the appropriate windowing length for feature
      extraction based on SODS and to determine a machine learning method that could
      provide higher accuracy in recognizing AF. METHOD: ECG features were extracted
      based on a dynamic system (DS) that uses a second-order differential equation to
      describe the short-term behavior of ECG signals according to the natural
      frequency (omega), damping coefficient, (xi), and forcing input (u). The
      extracted features were windowed into 2, 3, 4, 6, 8, and 10 second episodes to
      find the appropriate windowing size for AF signal processing. ANOVA and t-tests
      were used to determine the significant features. In addition, pattern recognition
      machine learning methods (an artificial neural network (ANN) and a support vector
      machine (SVM)) with k-fold cross validation (k-CV) were used to develop the ECG
      recognition system. RESULTS: Significant differences (p < 0.0001) were observed
      among all ECG groups (NSR, N, AF) using 2, 3, 4 and 6 second episodes for the
      features omega and u/omega; 4, 6 and 8 second episodes for features omega and u;
      4 and 6 second episodes for features omega, u and u/omega, and; 10 second
      episodes for the feature xi. The highest accuracy for AF recognition (AF, NSR)
      using ANN with k-CV was 95.3% using combination of features (omega and u; omega,
      u and u/omega) and SVM with k-CV was 95.0% using a combination of features omega,
      u and u/omega. CONCLUSION: This study found that 4 s is the most appropriate
      windowing length, using two features (omega and u) for AF detection with an
      accuracy of 95.3%. Moreover, the pattern recognition learning machine uses an ANN
      with 10-fold cross validation based on DS.

PMID- 27686712
TI  - EEG-based mild depressive detection using feature selection methods and
      classifiers.
AB  - BACKGROUND AND OBJECTIVE: Depression has become a major health burden worldwide,
      and effectively detection of such disorder is a great challenge which requires
      latest technological tool, such as Electroencephalography (EEG). This EEG-based
      research seeks to find prominent frequency band and brain regions that are most
      related to mild depression, as well as an optimal combination of classification
      algorithms and feature selection methods which can be used in future mild
      depression detection. METHODS: An experiment based on facial expression viewing
      task (Emo_block and Neu_block) was conducted, and EEG data of 37 university
      students were collected using a 128 channel HydroCel Geodesic Sensor Net (HCGSN).
      For discriminating mild depressive patients and normal controls, BayesNet (BN),
      Support Vector Machine (SVM), Logistic Regression (LR), k-nearest neighbor (KNN)
      and RandomForest (RF) classifiers were used. And BestFirst (BF), GreedyStepwise
      (GSW), GeneticSearch (GS), LinearForwordSelection (LFS) and RankSearch (RS) based
      on Correlation Features Selection (CFS) were applied for linear and non-linear
      EEG features selection. Independent Samples T-test with Bonferroni correction was
      used to find the significantly discriminant electrodes and features. RESULTS:
      Data mining results indicate that optimal performance is achieved using a
      combination of feature selection method GSW based on CFS and classifier KNN for
      beta frequency band. Accuracies achieved 92.00% and 98.00%, and AUC achieved
      0.957 and 0.997, for Emo_block and Neu_block beta band data respectively. T-test
      results validate the effectiveness of selected features by search method GSW.
      Simplified EEG system with only FP1, FP2, F3, O2, T3 electrodes was also explored
      with linear features, which yielded accuracies of 91.70% and 96.00%, AUC of 0.952
      and 0.972, for Emo_block and Neu_block respectively. CONCLUSIONS: Classification
      results obtained by GSW + KNN are encouraging and better than previously
      published results. In the spatial distribution of features, we find that left
      parietotemporal lobe in beta EEG frequency band has greater effect on mild
      depression detection. And fewer EEG channels (FP1, FP2, F3, O2 and T3) combined
      with linear features may be good candidates for usage in portable systems for
      mild depression detection.

PMID- 27686713
TI  - Cardiac arrhythmia beat classification using DOST and PSO tuned SVM.
AB  - BACKGROUND AND OBJECTIVE: The increase in the number of deaths due to
      cardiovascular diseases (CVDs) has gained significant attention from the study of
      electrocardiogram (ECG) signals. These ECG signals are studied by the experienced
      cardiologist for accurate and proper diagnosis, but it becomes difficult and time
      consuming for long-term recordings. Various signal processing techniques are
      studied to analyze the ECG signal, but they bear limitations due to the non
      stationary behavior of ECG signals. Hence, this study aims to improve the
      classification accuracy rate and provide an automated diagnostic solution for the
      detection of cardiac arrhythmias. METHODS: The proposed methodology consists of
      four stages, i.e. filtering, R-peak detection, feature extraction and
      classification stages. In this study, Wavelet based approach is used to filter
      the raw ECG signal, whereas Pan-Tompkins algorithm is used for detecting the R
      peak inside the ECG signal. In the feature extraction stage, discrete orthogonal
      Stockwell transform (DOST) approach is presented for an efficient time-frequency
      representation (i.e. morphological descriptors) of a time domain signal and
      retains the absolute phase information to distinguish the various non-stationary
      behavior ECG signals. Moreover, these morphological descriptors are further
      reduced in lower dimensional space by using principal component analysis and
      combined with the dynamic features (i.e based on RR-interval of the ECG signals)
      of the input signal. This combination of two different kinds of descriptors
      represents each feature set of an input signal that is utilized for
      classification into subsequent categories by employing PSO tuned support vector
      machines (SVM). RESULTS: The proposed methodology is validated on the baseline
      MIT-BIH arrhythmia database and evaluated under two assessment schemes, yielding
      an improved overall accuracy of 99.18% for sixteen classes in the category-based
      and 89.10% for five classes (mapped according to AAMI standard) in the patient
      based assessment scheme respectively to the state-of-art diagnosis. The results
      reported are further compared to the existing methodologies in literature.
      CONCLUSIONS: The proposed feature representation of cardiac signals based on
      symmetrical features along with PSO based optimization technique for the SVM
      classifier reported an improved classification accuracy in both the assessment
      schemes evaluated on the benchmark MIT-BIH arrhythmia database and hence can be
      utilized for automated computer-aided diagnosis of cardiac arrhythmia beats.

PMID- 27686715
TI  - Editorial.

PMID- 27686714
TI  - The reliability and validity of a clinical 3D freehand ultrasound system.
AB  - BACKGROUND AND OBJECTIVE: Acquiring large anatomical volumes in a feasible manner
      is useful for clinical decision-making. A relatively new technique called 3D
      freehand ultrasonography is capable of this by combining a conventional 2D
      ultrasonography system. Currently, a thorough analysis of this technique is
      lacking, as the analyses are dependent on the software implementation details and
      the choice of measurement systems. Therefore this study starts by making this
      implementation available under the form of an open-source software library to
      perform 3D freehand ultrasonography. Following that, reliability and validity
      analyses of extracting volumes and lengths will be carried out using two
      independent motion-tracking systems. METHODS: A PC-based ultrasonography device
      and two optical motion-tracking systems were used for data acquisition. An in
      house software library called Py3DFreeHandUS was developed to reconstruct (off
      line) the corresponding data into one 3D data set. Reliability and validity
      analyses of the entire experimental set-up were performed by estimating the
      volumes and lengths of ground truth objects. Ten water-filled balloons and six
      cross-wires were used. Repeat measurements were also performed by two experienced
      operators. RESULTS: The software library Py3DFreeHandUS is available online,
      along with the relevant documentation. The reliability analyses showed high intra
      and inter-operator intra-class correlation coefficient results for both volumes
      and lengths. The accuracy analysis revealed a discrepancy in all cases of around
      3%, which corresponded to 3 ml and 1 mm for volume and length measurements,
      respectively. Similar results were found for both of the motion-tracking systems.
      CONCLUSIONS: The undertaken analyses for estimating volume and lengths acquired
      with 3D freehand ultrasonography demonstrated reliable design measurements and
      suitable performance for applications that do not require sub-mm and -ml
      accuracy.

PMID- 27686716
TI  - Intestinal transport of Cylindrospermopsin using the Caco-2 cell line.
AB  - Cylindrospermopsin (CYN) is a cyanotoxin produced by various cyanobacterial
      species. It is a water soluble zwitterion, stable at extreme temperatures and pH.
      Despite the main route of exposure to CYN is through drinking water and food,
      there is a lack of data concerning its intestinal absorption and the mechanisms
      implicated. The aim of this study was to characterize the mechanisms involved in
      the intestinal absorption of CYN, using Caco-2 human cell line as a model of the
      intestinal epithelium. The results obtained in the present work increases the
      limited knowledge regarding CYN transport across the intestinal epithelium and
      identifies the paracellular route as an important pathway in CYN absorption. A
      minor carrier-mediated transcellular transport has been evidenced. This transport
      is not affected by low temperatures, suggesting that an active mechanism is not
      involved. Moreover, the transport through the intestinal monolayer is H+ and GSH
      dependent and Na+independent. The transport characteristics elucidated in this
      study prepare the ground for future studies directed at identifying transporters
      involved in the intestinal absorption of this toxin.

PMID- 27686717
TI  - A Home-Based Rehabilitation Intervention for Adults Living With HIV: A Randomized
      Controlled Trial.
AB  - A randomized controlled trial was conducted to investigate the effects of a 16
      week home-based rehabilitation (HBR) intervention on the quality of life,
      functional mobility, and functional capacity of adult people living with HIV
      (PLWH) on antiretroviral therapy in KwaZulu-Natal, South Africa. The intervention
      was carried out by community health care workers under the supervision of a
      qualified physical therapist. Participants in the control group received the
      standard of care as well as written health advice. While participants in the
      intervention group showed greater improvements across all outcome measures,
      between-group differences were nonsignificant. HBR for PLWH is a safe means of
      addressing the functional deficits experienced by PLWH and appears likely to
      improve quality of life. A task-shifting approach may be a feasible method of
      meeting the varied needs of PLWH, while at the same time potentially minimizing
      costs to already overburdened health care systems.

PMID- 27686718
TI  - Microbiome and food allergy.
AB  - Food allergy is a common disease affecting approximately 8% of children and 5% of
      adults. The prevalence has increased over the last two decades, suggesting an
      important environmental contribution to susceptibility. Studies have identified
      mode of birth, pet exposure, and having older siblings as being significant risk
      modifying factors in the development of food allergy. With the discovery that
      these factors significantly impact the composition of the intestinal microbiome,
      which is known to play a critical role in shaping the immune system, recent
      studies have begun to address the role of the intestinal microbiota in the
      development of food allergy. Studies in human cohorts support a dysbiosis in food
      allergy, and limited data suggest that this dysbiosis occurs early in life,
      preceding the onset of sensitization. Studies from animal models have clearly
      shown that the composition of the intestinal microbiota confers susceptibility to
      food allergy, and that there are organisms such as Clostridia species that are
      protective in the development of food allergy. Our understanding of microbial
      regulation of food allergy is in its nascency, but the state of the field
      supports an important contribution of intestinal microbes to susceptibility.
      Challenges going forward are to identify commensal-derived microorganisms that
      could be used therapeutically to prevent or perhaps treat food allergy.

PMID- 27686719
TI  - Developing a water-circulating column photobioreactor for microalgal growth with
      low energy consumption.
AB  - A water-circulating column photobioreactor (WCC-PBR) was developed to decrease
      bubble generation time and mixing time for growing microalgal biomass at low
      energy consumption. Bubble generation time was decreased by 60.4% and mixing time
      was decreased by 41.5% owing to an enhanced solution velocity with a water pump.
      Bubble residence time was decreased by 31.1% and mass transfer coefficient was
      decreased by 0.4% owing to a reduced distance between air aerator and solution
      surface. Microalgal growth rate was decreased by 12.7% from 128.9mg/Lday in an
      air-lifting column photobioreactor (ALC-PBR) to 112.6mg/Lday in a WCC-PBR because
      of the decrease in residence time of bubbles and an additional shear of cells in
      a water pump. However, total energy consumption of a WCC-PBR with an air
      compressor and a water pump was lower by 21.1% than that of an ALC-PBR with only
      an air compressor.

PMID- 27686720
TI  - Comparative biogas generation from fruit peels of fluted pumpkin (Telfairia
      occidentalis) and its optimization.
AB  - This study evaluated the potentials of fluted pumpkin fruit peels for biogas
      generation using three different pre-treatment methods (A, B, C) and the
      optimization of its process parameters. The physic-chemical characteristics of
      the substrates revealed it to be rich in nutrients and mineral elements needed by
      microorganisms. Gas chromatography analysis revealed the gas composition to be
      within the range of 58.5+/-2.5% Methane and 27+/-3% Carbon dioxide for all the
      three digestions. The study revealed that combination of three pre-treatment
      methods enhanced enormous biogas yield from the digested substrates as against
      the use of two methods and no pre-treatment experiment. Optimization of the
      generated biogas data revealed that RSM predicted higher gas yield than ANN, the
      latter gives higher accuracy and efficiency than the former. It is advocated that
      fluted pumpkin fruit peels be used for energy generation especially in the
      locations of its abundance.

PMID- 27686721
TI  - Fermentative hydrogen production in an up-flow anaerobic biofilm reactor
      inoculated with a co-culture of Clostridium acetobutylicum and Desulfovibrio
      vulgaris.
AB  - Dark fermentation systems often show low H2 yields and unstable H2 production, as
      the result of the variability of microbial dynamics and metabolic pathways.
      Recent batch investigations have demonstrated that an artificial consortium of
      two anaerobic bacteria, Clostridium acetobutylicum and Desulfovibrio vulgaris
      Hildenborough, may redirect metabolic fluxes and improve H2 yields. This study
      aimed at evaluating the scale-up from batch to continuous H2 production in an up
      flow anaerobic packed-bed reactor (APBR) continuously fed with a glucose-medium.
      The effects of various parameters, including void hydraulic retention time
      (HRTv), pH, and alkalinity, on H2 production performances and metabolic pathways
      were investigated. The results demonstrated that a stable H2 production was
      reached after 3-4days of operation. H2 production rates increased significantly
      with decreasing HRTv from 4 to 2h. Instead, H2 yields remained almost stable
      despite the change in HRTv, indicating that the decrease in HRTv did not affect
      the global metabolism.

PMID- 27686722
TI  - The type of carbohydrates specifically selects microbial community structures and
      fermentation patterns.
AB  - The impact on dark fermentation of seven carbohydrates as model substrates of
      lignocellulosic fractions (glucose, cellobiose, microcrystalline cellulose,
      arabinose, xylose, xylan and wheat straw) was investigated. Metabolic patterns
      and bacterial communities were characterized at the end of batch tests inoculated
      with manure digestate. It was found that hydrogen production was linked to the
      sugar type (pentose or hexose) and the degree of polymerisation. Hexoses produced
      less hydrogen, with a specific selection of lactate-producing bacterial community
      structures. Maximal hydrogen production was five times higher on pentose-based
      substrates, with specific bacterial community structures producing acetate and
      butyrate as main metabolites. Low hydrogen amounts accumulated from complex
      sugars (cellulose, xylan and wheat straw). A relatively high proportion of the
      reads was affiliated to Ruminococcaceae suggesting an efficient hydrolytic
      activity. Knowing that the bacterial community structure is very specific to a
      particular substrate offers new possibilities to design more efficient H2
      producing biological systems.

PMID- 27686723
TI  - Modelling of pretreatment and saccharification with different feedstocks and
      kinetic modeling of sorghum saccharification.
AB  - Experiments have been performed for pretreatment of sorghum, wheat straw and
      bamboo through high temperature alkali pretreatment with different alkaline
      loading and temperatures, and the data on extent of delignification in terms of
      the final compositions of cellulose, hemicellulose and lignin have been
      generated. Further, enzymatic saccharification has been carried out in all the
      cases to find the extent of conversion possible after 72h. The effect of
      different operating parameters on the extent of delignification and cellulose
      conversion are evaluated. This data is employed to develop a generalized multi
      feedstock and individual feedstock based models which can be used to determine
      the extent of delignification and cellulose conversion for any and specific
      biomass respectively with alkaline pretreatment and similar enzyme conditions as
      considered in the present study. Also, a kinetic model is developed and validated
      for sorghum for cellulosic conversion.

PMID- 27686724
TI  - Migration and risk assessment of heavy metals in sewage sludge during
      hydrothermal treatment combined with pyrolysis.
AB  - In this study, the immobilization and risk assessment of heavy metals (HMs) in
      sewage sludge (SS) during hydrothermal treatment combined with pyrolysis (HTP)
      was investigated. The experimental results showed that the immobilization of HMs
      in SS was significantly affected and that the eco-toxicity/risk of SS to the
      environment was reduced through HTP, in addition to the enhancement of
      dehydration and a reduction in the volume of the sewage sludge. After the HTP
      process, although the majority of HMs were accumulated in the biochar, the HMs
      could be transformed from bioavailable fractions to more stable fractions, such
      as the acid soluble/exchangeable fractions (F1) of Zn, Ni and Cd in the biochar,
      which decreased to less than 6.31%, 2.36% and 3.64%, respectively. Moreover, the
      leaching potential of HMs decreased after the HTP process.

PMID- 27686725
TI  - Insight into the solvent, temperature and time effects on the hydrogenolysis of
      hydrolyzed lignin.
AB  - The aim of this study is to explore the reaction mediums and conditions for
      producing high yield of valuable monomers from concentrated sulfuric acid
      hydrolyzed lignin. The solvent, temperature and time effects on the
      hydrogenolysis of hydrolyzed lignin were investigated under the catalysis of Pd/C
      and CrCl3. Supercritical methanol exhibits the best depolymerization performance,
      because of its unique diffusion, dissolution and acid-base properties.
      Afterwards, the influence of reaction temperature and time on depolymerization,
      repolymerization and coking during hydrogenolysis was examined in methanol. The
      high temperature is found to favor the depolymerization, with the beta-O-4
      linkages cleaved significantly. However, the repolymerization is promoted
      simultaneously, and a high amount of beta-beta groups form. These reactions are
      in constant competition with each other and the repolymerization is preferred at
      excessive high temperature, producing bulk char residues, that is coking. This
      study will provide a beneficial reference for the maximization of lignin waste
      valorization.

PMID- 27686726
TI  - Cannabidiol: a potential treatment for post Ebola syndrome?
AB  - Patients recovered from Ebola virus infection may experience short- and long-term
      physical, neuropsychological and social sequelae, including arthralgia,
      musculoskeletal pain, ophthalmic inflammation, auditory problems, fatigue,
      confusion, insomnia, short-term memory impairment, anxiety, depression and
      anorexia, all lasting from two weeks to more than two years. Currently there are
      no treatments for post Ebola sequelae. We hypothesize that cannabidiol (CBD) may
      attenuate some of these post Ebola sequelae, several of which have been
      postulated to result from inflammation and/or an autoimmune response. CBD has
      anti-inflammatory actions in various animal models. Clinical studies have shown
      that oral administration of CBD, compared to placebo, significantly reduces
      anxiety, has antinociceptive and anticonvulsant actions, and may be therapeutic
      for insomnia. Overall, CBD has a number of pharmacological effects that may
      significantly improve the mental and somatic health of patients suffering from
      post Ebola sequelae. In humans, CBD, at therapeutic doses, does not: 1) elicit
      dependence or tolerance; 2) significantly alter heart rate or blood pressure; 3)
      affect gastrointestinal transit; 4) produce significant cognitive or psychomotor
      impairments. Mild sedation and nausea are the most commonly reported adverse
      effects associated with CBD.CBD, based on its pharmacological effects and
      favorable safety profile, should be considered as a treatment for individuals
      with post Ebola sequelae.

PMID- 27686727
TI  - Implementing a care bundle approach reduces ventilator-associated pneumonia and
      delays ventilator-associated tracheobronchitis in children: differences according
      to endotracheal or tracheostomy devices.
AB  - OBJECTIVE: To reduce ventilator-associated infections (VARI) and improve outcomes
      for children. METHODS: This prospective interventional cohort study was conducted
      in a paediatric intensive care unit (PICU) over three periods: pre-intervention,
      early post-intervention, and late post-intervention. These children were on
      mechanical ventilation (MV) for >=48h. RESULTS: Overall, 312 children (11.9% of
      whom underwent tracheostomy) and 6187 ventilator-days were assessed. There was a
      significant reduction in ventilator-associated pneumonia (VAP) among
      tracheostomized patients (8.16, 3.27, and 0.65 per 1000 tracheostomy ventilation
      days before the intervention, after the general bundle implementation, and after
      the tracheostomy intervention, respectively). The median time from onset of MV to
      diagnosis of ventilator-associated tracheobronchitis (VAT) increased from 5.5 to
      48 days in the late post-intervention period (p=0.004), and was associated with a
      significant increase in median 28-day ventilator-free days and PICU-free days.
      Tracheostomy (odds ratio 7.44) and prolonged MV (odds ratio 2.75) were
      independent variables significantly associated with VARI. A trend towards a
      reduction in PICU mortality was observed, from 28.4% to 16.6% (relative risk
      0.58). CONCLUSIONS: The implementation of a care bundle to prevent VARI in
      children had a different impact on VAP and VAT, diminishing VAP rates and
      delaying VAT onset, resulting in reduced healthcare resource use. Tracheostomized
      children were at increased risk of VARI, but preventive measures had a greater
      impact on them.

PMID- 27686728
TI  - Quantitative intrahepatic HBV cccDNA correlates with histological liver
      inflammation in chronic hepatitis B virus infection.
AB  - BACKGROUND: The aim of this study was to determine the role of baseline hepatitis
      B virus (HBV) forming covalently closed circular DNA (HBV cccDNA) in liver
      inflammation in patients infected with HBV with serum alanine aminotransferase
      (ALT) levels under two times the upper limit of normal (2*ULN). METHODS: After
      liver biopsy and serum virological and biochemical marker screening, patients
      diagnosed with chronic HBV infection with serum ALT levels under 2*ULN and
      histological liver inflammation of less than grade G2 were prospectively
      recruited into this study. Recruitment took place between March 2009 and November
      2010 at the Center of Infectious Disease, Sichuan University. Patient virological
      and biochemical markers, as well as markers of liver inflammation, were
      monitored. RESULTS: A total of 102 patients were recruited and 68 met the
      inclusion criteria; the median follow-up was 4.1 years (range 3.9-5.2 years).
      During follow-up, 41 patients (60.3%) exhibited signs of inflammation. Baseline
      HBV cccDNA >1 copy/cell (odds ratio 9.43, p=0.049) and liver inflammation grade
      >=G1 (odds ratio 5.77, p=0.046) were both independent predictors of liver
      inflammation. CONCLUSIONS: A higher baseline intrahepatic HBV cccDNA level may
      increase the risk of liver inflammation. Further investigations will be required
      to validate HBV cccDNA as an intrahepatic virological marker of patients who
      require extended outpatient management.

PMID- 27686729
TI  - Molecular mechanisms underlying fibrosis and elastin destruction in childhood
      interstitial lung diseases.
AB  - OBJECTIVE: This study aimed to evaluate fibrosis and elastin destruction in
      childhood interstitial lung disease (chILD) patients. METHODS: Sixty patients and
      twenty healthy children were recruited. On admission, evaluation of chILD
      severity was made using Fan chILD score. Participants provided urine and blood
      samples. Plasma levels of transforming growth factor (TGF)-beta1, connective
      tissue growth factor (CCN2), soluble factor related apoptosis (sFas) and long non
      coding RNAs and urinary levels of desmosine/urinary creatinine (UDes/UCr) were
      measured. RESULTS: In patients, clinical findings were crackles (100.00%),
      tachypnea (65.00%), cardiomegaly (45.00%), digital clubbing (43.30%), cough
      (33.00%), cyanosis (26.70%), hepatomegaly (28.30%) and wheezes (23.30%).
      Categorizing of the patients with Fan chILD clinical score revealed that most
      patients 33.30% scored (3, symptomatic with abnormal saturation/cyanosis during
      exercise) then 28.30% scored (5, symptomatic with clinical and echocardiographic
      features of pulmonary hypertension), 18.30% scored (2, symptomatic with normal
      room air saturations), 15.00% scored (1, asymptomatic) and 5.00% scored (4,
      symptomatic with abnormal room air saturation/cyanosis at rest). TGF-beta1, CCN2,
      sFas, lncrRNA-2700086A05Rik relative gene expression and UDes/UCr levels were
      higher in patients than controls (P=0.002, P=0.001, P=0.001, P=0.001, P=0.001,
      respectively). In patients, significant positive correlations were found between
      TGF-beta1 and CCN2, sFas, UDes/UCr; between CCN2 and both sFas and UDes/UCr;
      between UDes/UCr and sFas. Morbidity and mortality rates were 46.70% and 10.00%,
      respectively. CONCLUSION: Markers of fibrosis (TGF-beta1, sFas, CCN2) and elastin
      destruction (UDes/UCr) were increased in chILD especially in patients with long
      disease duration. So blockage of their pathways signals may offer novel
      therapeutic targets.

PMID- 27686730
TI  - Publish (in English) or perish: The effect on citation rate of using languages
      other than English in scientific publications.
AB  - There is a tendency for non-native English scientists to publish exclusively in
      English, assuming that this will make their articles more visible and cited. We
      tested this hypothesis by comparing the effect of language on the number of
      citations of articles published in six natural sciences journals from five
      countries that publish papers in either English or other languages. We analyzed
      the effect of language (English vs non-English), paper length, and year of
      publication on the number of citations. The articles published in English have a
      higher number of citations than those published in other languages, when the
      effect of journal, year of publication, and paper length are statistically
      controlled. This may result because English articles are accessible to a larger
      audience, but other factors need to be explored. Universities and scientific
      institutions should be aware of this situation and improve the teaching of
      English, especially in the natural sciences.

PMID- 27686731
TI  - Rehabilitating mussel beds in Coffee Bay, South Africa: Towards fostering
      cooperative small-scale fisheries governance and enabling community upliftment.
AB  - Along the coast of South Africa, marine resources play a significant role in
      supporting livelihoods and contributing to food security in impoverished rural
      communities. Post-apartheid fisheries laws and policies have begun to address
      traditional fishing rights and development needs, and new management arrangements
      are being implemented. One such initiative has been the Mussel Rehabilitation
      Project in Coffee Bay, which piloted a resource rehabilitation technique at
      several over-exploited fishing sites. Mussel stocks in these exploited areas had
      dropped to under 1 % mussel cover, and during the project period, stocks
      increased to >80 % cover, supporting a sustainable harvest well above national
      daily bag limits. This stock enhancement was achieved only after the project had
      started to address social challenges such as the lack of local management
      institutions and the need to enhance food security. The project embarked on
      training and institution-building; it formed a robust community mussel management
      committee; and developed a local resource management plan, facilitating increased
      community participation in the day-to-day management of the resource. The project
      also saw the initiation of various ancillary projects aimed at improving food
      security and stimulating the local economy and hence alleviating pressure on the
      marine resources. Here we review this 10-year project's outcomes, and present
      lessons for small-scale fisheries governance in South Africa and internationally.
      We show, through empirical experience, that balancing stock rebuilding needs in a
      context of widespread poverty and dependency on natural resources by a local
      fisher community can only be addressed through an integrated approach to
      development. Participation of resource users and a thorough understanding of the
      local context are imperative to negotiating appropriate small-scale fisheries
      governance approaches. We recommend that the implementation of South Africa's
      newly minted Small-Scale Fisheries Policy should begin with bottom-up,
      demonstrative resource management measures such as mussel rehabilitation. This
      type of initiative can deliver short-term food security benefits and foster
      social learning towards sustainable and cooperative fisheries governance.

PMID- 27686733
TI  - Hydrops Fetalis Associated with Compound Heterozygosity for Hb Zurich-Albisrieden
      (HBA2: C.178G > C) and the Southeast Asian (- -SEA/) Deletion.
AB  - Hb Zurich-Albisrieden [HBA2: c.178G > C; alpha59(E8)Gly->Arg (alpha2)] is a rare
      nondeletional alpha-thalassemia (alpha-thal) that results from a nucleotide
      substitution at codon 59 of the alpha2-globin gene. In this report, we present a
      fetus with cardiomegaly, enlarged placenta and increased middle cerebral artery
      peak systolic velocity (MCA-PSV) at 25 weeks' gestation. Fetal blood sampling
      revealed the severe anemia [hemoglobin (Hb) level being 5.5 g/dL] and Hb H
      (beta4) disease-like hematological findings with Hb Bart's (gamma4) level of
      30.7%. Molecular analysis of the family found that the father was an Hb Zurich
      Albisrieden carrier, the mother heterozygous for the - -SEA alpha0-thal deletion,
      and the fetus was a compound heterozygote for Hb Zurich-Albisrieden and the - 
      SEA alpha0-thal deletion. Therefore, this was a rare case of Hb Bart's hydrops
      fetalis associated with Hb Zurich Albisrieden.

PMID- 27686734
TI  - Single-dose acarbose decreased glucose-dependent insulinotropic peptide and
      glucagon levels in Chinese patients with newly diagnosed type 2 diabetes mellitus
      after a mixed meal.
AB  - BACKGROUND: Acarbose slows down the intestinal absorption of carbohydrates, but
      its effects on the secretion of incretins are still poorly known. This study
      aimed to examine the effects of single-dose acarbose on the secretion of
      incretins in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
      METHODS: In this pilot study, twenty-three patients diagnosed with T2DM were
      randomly assigned to the oral glucose tolerance test (OGTT) group (n = 11) and
      the mixed meal test (MMT) group (n = 12). Fourteen subjects with normal OGTT were
      included as controls. Plasma glucose, insulin, glucagon, glucagon-like peptide-1
      (GLP-1), and glucose-dependent insulinotropic peptide (GIP) were measured at 0
      (fasting), 15, 30, 60, 90, and 120 min after nutrient load. A week later,
      controls underwent MMT, the OGTT group underwent OGTT receiving 100 mg acarbose,
      and the MMT group underwent MMT receiving 100 mg acarbose. The same blood markers
      were measured again. RESULTS: No significant difference was observed in the OGTT
      group before and after administering acarbose. In the MMT group, postprandial
      levels of glucose (P < 0.01), insulin (P < 0.01), glucagon at 15 min (P < 0.05),
      glucagon area under the curve (AUC) (P < 0.05), GIP levels at 30 min (P < 0.05),
      and GIP AUC (P < 0.05) were decreased after receiving acarbose with a mixed meal,
      but GLP-1 levels and GLP-1 AUC did not change. CONCLUSIONS: Single-dose acarbose
      could reduce the secretion of GIP and glucagon after a mixed meal in patients
      with newly diagnosed T2DM. The influence of acarbose on incretin levels could be
      related to the types of carbohydrate being consumed. TRIAL REGISTRATION: This
      study was registered with the Chinese Clinical Trial Registry (Registration
      Number: ChiCTR-TRC-14004260 , Date of Registration: 2014-01-19).

PMID- 27686732
TI  - Long non-coding RNAs: potential new biomarkers for predicting tumor invasion and
      metastasis.
AB  - Long non-coding RNAs (lncRNAs) play important roles in malignant neoplasia.
      Indeed, many hallmarks of cancer define that the malignant phenotype of tumor
      cells are controlled by lncRNAs. Despite a growing number of studies highlighting
      their importance in cancer, there has been no systematic review of metastasis
      associated lncRNAs in various cancer types. Accordingly, we focus on the key
      metastasis-related lncRNAs and outline their expression status in cancer tissues
      by reviewing the previous stuides, in order to summarize the nowadays research
      achivements for lncRNAs related to cancer metastasis. Medline, EMBASE, as well as
      PubMed databases were applied to study lncRNAs which were tightly associated with
      tumor invasion and metastasis. Up to now, a substantial number of lncRNAs have
      been found to have important biological functions. In this review, according to
      their various features in cancer, lncRNAs were roughly divided into three
      categories: promoting tumor invasion and metastasis, negative regulation of tumor
      metastasis and with dual regulatory roles. The present studies may establish the
      foundation for both further research on the mechanisms of cancer progression and
      future lncRNA-based clinical applications.

PMID- 27686736
TI  - Commentary to "Worldwide prevalence of hypospadias".

PMID- 27686735
TI  - Assessing the level of evidence on transfer and transition in young people with
      chronic conditions: protocol of a scoping review.
AB  - BACKGROUND: Life-long specialized care is of the utmost importance to safeguard
      longevity as well as the quality of life in children diagnosed with a chronic
      condition (CC). Provision of life-long care, however, infers transfers to
      different settings in line with person's development status. Young people with CC
      (10-25 years) will transfer care from a pediatric towards an adult-oriented care
      setting. As a transfer of care is associated with a change of care context,
      healthcare team, responsibilities, expectations, and roles, patients need to be
      prepared for this alteration. One type of preparatory intervention is the
      provision of transitional care. Transition prepares adolescents for the
      responsibilities associated with adult care and age through support, education,
      skills demonstration, and guidance. The past decades, increasing attention has
      been paid towards the concept of transfer and transition, both in clinical
      practice and research. Numerous consensus papers have been established,
      emphasizing the need for the establishment of a transition program for young
      patients with CC. To date, it remains, however, unclear what the overall level of
      evidence is on transfer and transition in this population. This scoping review
      aims to analyze and determine the level of evidence of published literature on
      transfer and transition of young people diagnosed with CC. METHOD: MEDLINE,
      CINAHL, Scopus, and Web of Science databases will be searched for relevant
      publications. Any publication in English, Spanish, German, or French, related to
      transfer and/or transition in young people with CC will be included. A three
      staged approach will identify relevant papers, comprising systematic database
      searches, application of snowball method, and citation searching. Study selection
      will be performed through screening of titles/abstracts followed by a full-text
      assessment using a standardized selection form. Data extraction will be performed
      by two reviewers independently using a pilot-tested, standardized form.
      Descriptive statistics and content analysis will be applied to present the
      results. Bibliometric visualization techniques will be performed with VOS
      viewer(r). DISCUSSION: Our review will map the overall level of evidence of
      published literature on transfer and transition in young people with CC. It will
      provide guidance for future research initiatives, clinical practice, and policy
      makers.

PMID- 27686737
TI  - New revised simple models for interactive wild and sterile mosquito populations
      and their dynamics.
AB  - Based on previous research, we formulate revised, new, simple models for
      interactive wild and sterile mosquitoes which are better approximations to real
      biological situations but mathematically more tractable. We give basic
      investigations of the dynamical features of these simple models such as the
      existence of equilibria and their stability. Numerical examples to demonstrate
      our findings and brief discussions are also provided.

PMID- 27686738
TI  - Variation of anthocyanins and other major phenolic compounds throughout the
      ripening of four Portuguese blueberry (Vaccinium corymbosum L) cultivars.
AB  - Blueberries are widely recognised as one of the richest sources of bioactive
      compounds, among which are anthocyanins, though the ripeness of berries has been
      reported as affecting the phytochemical composition of fruits. Therefore, the
      present work aimed to evaluate the variation of anthocyanins, and other major
      phenolics, throughout five ripening stages in four blueberry cultivars. The
      results showed that the antioxidant capacity and anthocyanin content increased
      during ripening, reaching the highest values when the blueberries are collected
      from bunches comprised of 75% ripe blueberries. Antagonistically, the amount of
      phenolic acid decreases, while the quercetin-3-glucoside levels remain stable.
      Furthermore, Goldtraube blueberries appear to possess, systematically, higher
      amounts of phenolic compounds than the other cultivars studied. Thus, when
      seeking the highest yield of anthocyanins, the preferred harvest should occur in
      bunches that contain ca 75% of ripe blueberries and, considering the cultivars
      assayed, the Goldtraube cultivar appears to be the richest in phenolic compounds.

PMID- 27686739
TI  - The impacts of initial and relative dose intensity of R-CHOP on outcomes of
      elderly patients with diffuse large B-cell lymphoma.

PMID- 27686740
TI  - Efficacy of poly (ADP-ribose) polymerase inhibitor olaparib against head and neck
      cancer cells: Predictions of drug sensitivity based on PAR-p53-NF-kappaB
      interactions.
AB  - Poly (ADP-ribose) polymerase (PARP) is a key molecule in the DNA damage response
      (DDR), which is a major target of both chemotherapies and radiotherapies. PARP
      inhibitors therefore comprise a promising class of anticancer therapeutics. In
      this study, we evaluated the efficacy of the PARP inhibitor olaparib, and also
      sought to identify the mechanism and predictive marker associated with olaparib
      sensitivity in head and neck cancer (HNC) cells. A total of 15 HNC cell lines,
      including AMC HNC cells, were tested. AMC-HN3 and HN4 exhibited stronger
      responses to olaparib. Among cisplatin-resistant cell lines, only AMC HN9-cisR
      cells were significantly suppressed by olaparib. We found that basal poly (ADP
      ribose) (PAR) levels, but not PARP-1 levels, correlated with olaparib
      sensitivity. AMC-HN3 and HN4 cells exhibited higher basal levels of NF-kappaB
      that decreased significantly after olaparib treatment. In contrast, apoptotic
      proteins were intrinsically expressed in AMC-HN9-cisR cells. As interference with
      p53 expression led to NF-kappaB reactivation, we concluded that elevated basal
      PAR and NF-kappaB levels are predictive of olaparib responsiveness in HNC cells;
      in addition, olaparib inhibits HNC cells via PAR-p53-NF-kappaB interactions.

PMID- 27686741
TI  - Maternal high-fat diet during lactation impairs thermogenic function of brown
      adipose tissue in offspring mice.
AB  - Maternal obesity and high-fat diet (HFD) predisposes offspring to obesity and
      metabolic diseases. Due to uncoupling, brown adipose tissue (BAT) dissipates
      energy via heat generation, mitigating obesity and diabetes. The lactation stage
      is a manageable period for improving the health of offspring of obese mothers,
      but the impact of maternal HFD during lactation on offspring BAT function is
      unknown. To determine, female mice were fed either a control or HFD during
      lactation. At weaning, HFD offspring gained more body weight and had greater body
      fat mass compared to the control, and these differences maintained into
      adulthood, which correlated with glucose intolerance and insulin resistance in
      HFD offspring. Adaptive thermogenesis of BAT was impaired in HFD offspring at
      weaning. In adulthood, HFD offspring BAT had lower Ucp1 expression and
      thermogenic activity. Mechanistically, maternal HFD feeding during lactation
      elevated peripheral serotonin, which decreased the sensitivity of BAT to
      sympathetic beta3-adrenergic signaling. Importantly, early postnatal metformin
      administration decreased serotonin concentration and ameliorated the impairment
      of offspring BAT due to maternal HFD. Our data suggest that attenuation of BAT
      thermogenic function may be a key mechanism linking maternal HFD during lactation
      to persisted metabolic disorder in the offspring.

PMID- 27686743
TI  - Bioengineered valves for the venous circulation.
AB  - INTRODUCTION: Chronic insufficiency of lower extremity venous valves represents a
      frequent structural disorder of the vascular system being responsible for a
      substantial global disease load. While in the field of superficial valve
      insufficiency surgical as well as endoluminal interventions represent good
      therapeutic options with high rates of complete remission of symptoms, only
      limited options exist in the field of deep venous reflux today. Bioengineered,
      autologous cell-based, endothelialized valve constructs may open up new
      therapeutic options in these patients, potentially offering novel treatment
      options in cases with severe insufficiency of deep venous segments in the future.
      Areas covered: This review summarizes previous reports focusing on venous valve
      replacement and bioengineering, also including first preclinical in vivo studies
      and first clinical trials in patients. In particular, the aspects of current
      technical and medical limitations of venous valve bioengineering approaches
      preventing clinical translation and potential solutions by upcoming technologies
      will be discussed as part of this review. Expert commentary: Bioengineered
      replacement valves may open up novel options in the treatment of venous valve
      disease in defined patient groups in the future. However, preventing
      thromboembolic complications will remain the bottle-neck for clinical translation
      of the technologies involved.

PMID- 27686742
TI  - Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus.
AB  - Diverse pathogenic agents often utilize overlapping host networks, and hub
      proteins within these networks represent attractive targets for broad-spectrum
      drugs. Using bacterial toxins, we describe a new approach for discovering broad
      spectrum therapies capable of inhibiting host proteins that mediate multiple
      pathogenic pathways. This approach can be widely used, as it combines genetic
      based target identification with cell survival-based and protein function-based
      multiplex drug screens, and concurrently discovers therapeutic compounds and
      their protein targets. Using B-lymphoblastoid cells derived from the HapMap
      Project cohort of persons of African, European, and Asian ancestry we identified
      host caspases as hub proteins that mediate the lethality of multiple pathogenic
      agents. We discovered that an approved drug, Bithionol, inhibits host caspases
      and also reduces the detrimental effects of anthrax lethal toxin, diphtheria
      toxin, cholera toxin, Pseudomonas aeruginosa exotoxin A, Botulinum neurotoxin,
      ricin, and Zika virus. Our study reveals the practicality of identifying host
      proteins that mediate multiple disease pathways and discovering broad-spectrum
      therapies that target these hub proteins.

PMID- 27686744
TI  - Stille coupling via C-N bond cleavage.
AB  - Cross-coupling is a fundamental reaction in the synthesis of functional
      molecules, and has been widely applied, for example, to phenols, anilines,
      alcohols, amines and their derivatives. Here we report the Ni-catalysed Stille
      cross-coupling reaction of quaternary ammonium salts via C-N bond cleavage.
      Aryl/alkyl-trimethylammonium salts [Ar/R-NMe3]+ react smoothly with arylstannanes
      in 1:1 molar ratio in the presence of a catalytic amount of commercially
      available Ni(cod)2 and imidazole ligand together with 3.0 equivalents of CsF,
      affording the corresponding biaryl with broad functional group compatibility. The
      reaction pathway, including C-N bond cleavage step, is proposed based on the
      experimental and computational findings, as well as isolation and single-crystal
      X-ray diffraction analysis of Ni-containing intermediates. This reaction should
      be widely applicable for transformation of amines/quaternary ammonium salts into
      multi-aromatics.

PMID- 27686745
TI  - Flexible all-polymer waveguide for low threshold amplified spontaneous emission.
AB  - The fabrication of all polymer optical waveguides, based on a highly fluorescent
      conjugated polymer (CP) poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) and
      a mechanically flexible and biodegradable polymer, cellulose acetate (CA), is
      reported. The replication by hot embossing of patterned surfaces in CA
      substrates, onto which high quality F8BT films can be easily processed by spin
      coating, is exploited to produce an entirely plastic device that exhibits low
      optical loss and low threshold for amplified spontaneous emission (ASE). As a
      result, highly transparent and flexible waveguides are obtained, with excellent
      optical properties that remain unaltered after bending, allowing them to be
      adapted in various flexible photonic devices.

PMID- 27686746
TI  - In low protein diets, microRNA-19b regulates urea synthesis by targeting SIRT5.
AB  - Ammonia detoxification, which takes place via the hepatic urea cycle, is
      essential for nitrogen homeostasis and physiological well-being. It has been
      reported that a reduction in dietary protein reduces urea nitrogen. MicroRNAs
      (miRNAs) are major regulatory non-coding RNAs that have significant effects on
      several metabolic pathways; however, little is known on whether miRNAs regulate
      hepatic urea synthesis. The objective of this study was to assess the miRNA
      expression profile in a low protein diet and identify miRNAs involved in the
      regulation of the hepatic urea cycle using a porcine model. Weaned 28-days old
      piglets were fed a corn-soybean normal protein diet (NP) or a corn-soybean low
      protein diet (LP) for 30 d. Hepatic and blood samples were collected, and the
      miRNA expression profile was assessed by sequencing and qRT-PCR. Furthermore, we
      evaluated the possible role of miR-19b in urea synthesis regulation. There were
      25 differentially expressed miRNAs between the NP and LP groups. Six of these
      miRNAs were predicted to be involved in urea cycle metabolism. MiR-19b negatively
      regulated urea synthesis by targeting SIRT5, which is a positive regulator of
      CPS1, the rate limiting enzyme in the urea cycle. Our study presented a novel
      explanation of ureagenesis regulation by miRNAs.

PMID- 27686747
TI  - Neutrophil-to-lymphocyte ratio is a reliable marker of treatment response in
      rheumatoid arthritis patients during tocilizumab therapy.
AB  - OBJECTIVE: To investigate the reliable markers reflecting treatment response
      better than the traditional inflammatory indices in patients with rheumatoid
      arthritis (RA) receiving tocilizumab therapy. METHODS: A total of 58 RA patients
      treated with tocilizumab for more than six months from January 2013 to December
      2014 were initially included. Flares were defined as events that required steroid
      dose escalation, intra-articular steroid injections, or switching tocilizumab to
      other biologic agents. The clinical and laboratory data were retrospectively
      collected from electronic medical records. RESULTS: Of the 52 patients except for
      six patients who were excluded, 16 experienced flares, and 36 were stable during
      tocilizumab therapy. The C-reactive protein (CRP) level did not significantly
      differ between a stable state before flares and at flares. Compared with those at
      the preflare time point, erythrocyte sedimentation rate (ESR), and neutrophil to
      lymphocyte ratio (NLR) were significantly higher at flares; however, ESR levels
      (n = 9) were within the normal limit or decreased (n = 4) at flares.
      Interestingly, NLR increased at flares in all but one patient in the flare group.
      CONCLUSION: NLR is a more reliable marker than ESR or CRP for evaluating the
      disease activity in patients with RA during tocilizumab therapy.

PMID- 27686748
TI  - Accuracy Improvement for Predicting Parkinson's Disease Progression.
AB  - Parkinson's disease (PD) is a member of a larger group of neuromotor diseases
      marked by the progressive death of dopamineproducing cells in the brain.
      Providing computational tools for Parkinson disease using a set of data that
      contains medical information is very desirable for alleviating the symptoms that
      can help the amount of people who want to discover the risk of disease at an
      early stage. This paper proposes a new hybrid intelligent system for the
      prediction of PD progression using noise removal, clustering and prediction
      methods. Principal Component Analysis (PCA) and Expectation Maximization (EM) are
      respectively employed to address the multi-collinearity problems in the
      experimental datasets and clustering the data. We then apply Adaptive Neuro-Fuzzy
      Inference System (ANFIS) and Support Vector Regression (SVR) for prediction of PD
      progression. Experimental results on public Parkinson's datasets show that the
      proposed method remarkably improves the accuracy of prediction of PD progression.
      The hybrid intelligent system can assist medical practitioners in the healthcare
      practice for early detection of Parkinson disease.

PMID- 27686749
TI  - Mepacrine as successful monotherapy for refractory Jessner-Kanof disease: still
      an important drug in the dermatologic armamentarium.
AB  - INTRODUCTION: Jessner-Kanof disease (JKD), a lymphocytic infiltration of the
      skin, can be difficult to treat. Mepacrine (quinacrine), an anti-malarial less
      available in Belgium, may be beneficial. PATIENTS AND METHODS: Two female
      patients with biopsy-proven and therapy-resistant JKD, not responding to topical
      and systemic corticosteroids, (hydroxy-)chloroquine and/or dapsone, were treated
      with mepacrine 100 mg daily. RESULTS: In both patients an amelioration was
      observed during the first month of treatment, and clinical remission was obtained
      by the fourth month, without any side-effects. In both cases, the dose could be
      tapered to three times weekly. DISCUSSION: JKD is strongly related to lupus
      erythematosus (tumidus), and although spontaneous remissions may occur, it is
      notoriously difficult to treat. Mepacrine may be initiated as an add-on therapy
      to (hydroxy-)chloroquine, but also as monotherapy. A dose of 100 mg a day,
      tapered to weekly doses once remission is obtained, seems feasible. Except for
      (mild) yellow skin discoloration, the drug has few side-effects, and offers the
      advantage of not displaying retinal toxicity. CONCLUSION: Mepacrine is still a
      useful and safe drug for treating cutaneous lupus erythematosus and related skin
      conditions, such as refractory JKD in particular. Its future availability, also
      in Belgium, is therefore important.

PMID- 27686750
TI  - Caffeoylquinic acids from antiplasmodial active extract of Xanthium cavanillesii
      fruits and their molecular modelling studies.
AB  - The antiplasmodial active extract of Xanthium cavanillesii contains 3,4
      dicaffeoyl quinic acid (3,4-DCQA), 3,5-dicaffeoyl quinic acid (3,5-DCQA) and
      1,3,5-tricaffeoyl quinic acid (1,3,5-TCQA). These results inspired us to
      investigate the interaction of these molecules with a promising validated target
      of Plasmodium, PfATP6 orthologue of mammalian Ca+2-ATPase. Models of this
      receptor were obtained through comparative modelling. Afterwards, molecular
      docking studies were used to identify possible interaction modes of these
      caffeoyl quinic derivatives on the binding site. The 1,3,5-TCQA had the best
      energy, but all of these had better energy than thapsigargin, a non-competitive
      inhibitor of the sarco/endoplasmatic reticulum Ca+2-ATPase (SERCA).

PMID- 27686752
TI  - Patient Satisfaction with Pharmacist-Led Collaborative Follow-Up Care in an
      Ambulatory Rheumatology Clinic.
AB  - OBJECTIVES: Patient satisfaction is known to increase with pharmacist
      intervention in general outpatient clinics and with nurse-led care in
      rheumatology clinics. The aim of the present study was to describe and compare
      patient satisfaction with two different types of care: a pharmacist physician
      collaborative model and a traditional physician model in a rheumatology clinic
      setting. METHODS: A cross-sectional survey of inflammatory arthritis patients
      seen during a follow-up visit in Edmonton, Alberta, Canada, was conducted over a
      ten-week period. Patient satisfaction was measured using a modified version of
      the validated Leeds Satisfaction Questionnaire, which uses a five-point Likert
      scale to measure six dimensions of satisfaction, and compared between the
      collaborative care and traditional physician models. RESULTS: A total of 62
      patients completed the questionnaire (21 collaborative care and 41 traditional
      physician model). The average age of respondents was 52 years and the majority
      were female. The mean score for satisfaction across the six dimensions was 4.56
      in the collaborative care group and 4.30 in the traditional physician group (p =
      0.02). Patient satisfaction in the collaborative care group was consistently
      higher across all dimensions. No difference was noted between participants seen
      for the first time compared with those seen two or more times by the pharmacist.
      CONCLUSIONS: A collaborative care model can exceed the already high expectations
      for care of patients with inflammatory arthritis. Our findings support the role
      of pharmacists using a collaborative care approach to care for patients in
      rheumatology clinics.

PMID- 27686753
TI  - Overlapping Electronic States with Nearly Parallel Transition Dipole Moments in
      Reduced Anionic Flavin Can Distort Photobiological Dynamics.
AB  - Chromophoric biomolecules are exploited as reporters of a diverse set of
      phenomena, acting as internal distance monitors, environment and redox sensors,
      and endogenous imaging probes. The extent to which they can be exploited is
      dependent on an accurate knowledge of their fundamental electronic properties.
      Arguably of greatest importance is a precise knowledge of the direction(s) of the
      absorption transition dipole moment(s) (TDMs) in the molecular frame of
      reference. Such is the case for flavins, fluorescent redox cofactors utilized for
      ground- and excited-state redox and photochemical processes. The directions of
      the TDMs in oxidized and semiquinone flavins were characterized decades ago, and
      the details of charge redistribution in these forms have also been studied by
      Stark spectroscopy. The electronic structure of the fully reduced hydroquinone
      anionic state, FlH-, however, has been the subject of unfounded assumptions and
      estimates about the number and direction of TDMs in FlH-, as well the electronic
      structure changes that occur upon light absorption. Here we have used Stark
      spectroscopy to measure the magnitude and direction of charge redistribution in
      FlH- upon optical excitation. These data were analyzed using TD-DFT calculations.
      The results show unequivocally that not one but two nearly orientation-degenerate
      electronic transitions are required to explain the 340-500 nm absorption spectral
      range, demolishing the commonly held assumption of a single transition. The
      difference dipole moments for these states show that electron density shifts
      toward the xylene ring for both transitions. These measurements force a
      reappraisal of previous studies that have used erroneous assumptions and
      unsubstantiated estimates of these quantities. The results put future optical
      studies of reduced flavins/flavoproteins on a firm photophysical footing.

PMID- 27686751
TI  - Characteristics of Qualitative Descriptive Studies: A Systematic Review.
AB  - Qualitative description (QD) is a term that is widely used to describe
      qualitative studies of health care and nursing-related phenomena. However,
      limited discussions regarding QD are found in the existing literature. In this
      systematic review, we identified characteristics of methods and findings reported
      in research articles published in 2014 whose authors identified the work as QD.
      After searching and screening, data were extracted from the sample of 55 QD
      articles and examined to characterize research objectives, design justification,
      theoretical/philosophical frameworks, sampling and sample size, data collection
      and sources, data analysis, and presentation of findings. In this review, three
      primary findings were identified. First, although there were some
      inconsistencies, most articles included characteristics consistent with the
      limited available QD definitions and descriptions. Next, flexibility or
      variability of methods was common and effective for obtaining rich data and
      achieving understanding of a phenomenon. Finally, justification for how a QD
      approach was chosen and why it would be an appropriate fit for a particular study
      was limited in the sample and, therefore, in need of increased attention. Based
      on these findings, recommendations include encouragement to researchers to
      provide as many details as possible regarding the methods of their QD studies so
      that readers can determine whether the methods used were reasonable and effective
      in producing useful findings. (c) 2016 Wiley Periodicals, Inc.

PMID- 27686754
TI  - Reliability for detecting oropharyngeal aspiration in children using cervical
      auscultation.
AB  - PURPOSE: Limited data exist that support the reproducibility of cervical
      auscultation (CA) use in children. This study aimed to determine the reliability
      of CA in detecting oropharyngeal aspiration (OPA) in children within a controlled
      environment. METHOD: This observational study included eight speech-language
      pathologists who rated clips of 40 normal and 40 OPA swallowing sounds on two
      separate occasions (i.e.160 sound clips rated by each speech-language
      pathologist) to comprise a total of 1280 swallow clips rated. Swallowing sound
      clips were collected from (1) a volunteer sample of 20 healthy children from the
      general community (mean 16.2 +/- 10.7 months; 65% female); (2) a referred sample
      of 19 children with demonstrated OPA (mean 22.8 +/- 25.5 months; 36.8% female),
      as determined on videofluoroscopic swallow studies (VFSS) using the Penetration
      Aspiration Scale (PAS) (>=6 score). RESULT: Inter-rater reliability was very good
      (kappa =0.81, 95%CI 0.79-0.84). Intra-rater reliability for each rater was good
      to very good (kappa range 0.72-0.98). Overall sensitivity was 93.9% (95%CI 91.8
      95.6) and specificity was 94.5% (95%CI 92.5-96.2). High reliability values were
      found for the detection of OPA versus normal swallows using CA alone. CONCLUSION:
      Future research should investigate the use of CA in a variety of clinical
      settings with less environmental control before CA can be advocated for use in
      routine clinical practice.

PMID- 27686758
TI  - [Discussion of HIV control and prevention strategies].
AB  - Expansion of HIV testing and ART treatment are core strategies for achieving the
      ambitious global goal of ending the HIV epidemic by the end of 2030, and
      achieving the "90-90-90" target by 2020. In China, great progress in HIV control
      and prevention has been made; however, there is room to enhance the effectiveness
      of HIV-related strategies. In addition, some implemented strategies have not
      achieved their expected output. To confront the challenge of sexual transmission
      of HIV, which is the main route of transmission in China, more targeted HIV
      prevention strategies that lead to their expected outcomes are essential. It is
      important to strengthen existing strategies that have been proved effective.
      However, it is also critical to create innovative strategies, and there are five
      approaches to achieve this. First, a holistic perspective should be adopted, to
      better understand the current situation and problems. This means intervention
      strategies should give serious consideration of how to meet the sociocultural
      needs of target populations rather than merely carry out behavioral
      interventions. Second, community-based HIV prevention settings should have more
      important roles in providing HIV-related health care services. Moreover, to
      improve the effectiveness of these strategies, a problem-led working style should
      be integrated into HIV prevention measures overall. Third, thoroughly analyzing
      characteristics of the current HIV epidemic using more evidence-based
      considerations must be undertaken, to better control HIV sexual transmission.
      Fourth, continued improvement of AIDS prevention and control mechanisms is
      needed, to ensure their sustainable development. Last, it is necessary to involve
      more NGOs in HIV prevention work by strengthening their management and working
      capacities to provide HIV-related services. Also needed is further improvement in
      both technical and management capacities, so as to build a stable basis for
      effective response.

PMID- 27686759
TI  - [The social marketing models and policy advices for HIV rapid testing initiated
      by non-govermental organization].
AB  - Currently, a growing number of community-based organizations are providing rapid
      HIV testing service in various forms, some people with specific needs also
      purchase HIV rapid test papers through online sales channels, those imply that
      the demand of HIV self-test is in increasing year by year.In this paper, aims to
      understand the current situation of HIV rapid test led by CBOs and the approach,
      strategies and results of social marketing by means of expert interviews and site
      visits. Hope to illustrate the current situation, and make recommendations for
      future work.

PMID- 27686760
TI  - [Expert consensus on the detection methods for food-borne pathogenic
      microorganisms].

PMID- 27686761
TI  - [Application of " Internet Plus" AIDS prevention services among men who have sex
      with men in Guangzhou, China: results from 2010 to 2015].
AB  - Objective: To introduce the development strategy of " Internet Plus" AIDS
      prevention services and its implementation results from 2010 to 2015 in
      Guangzhou, China. Methods: A gay men's health column was created for an active
      website aimed at men who have sex with men(MSM), in collaboration with local
      community organizations and the Guangzhou CDC. We designed intervention
      tools(including scenario-based applications and HIV risk self-assessment
      systems)and an online HIV testing service platform, integrated with applied
      psychology and behavioral theory as well as the " Internet Plus" concept, to
      intervene in HIV infection risk factors among MSM. Data of clients who accessed
      the " Internet Plus" AIDS services from 2010 to 2015 were used to evaluate
      service operation. Six-year consecutive surveys, conducted between April and July
      of each service year, were collected using a national AIDS sentinel surveillance
      questionnaire. For each year of surveillance, information on HIV prevalence, HIV
      interventions received during the past year, unprotected anal intercourse in the
      past 6 months, and HIV testing in the past year were compared using the chi
      squared(chi2)test, to roughly reflect the effect of"Internet Plus" AIDS
      prevention services. Results: As of 31 December 2015, a total of 34 395 MSM had
      received " Internet Plus" services and HIV testing. The number of MSM tested
      increased from 2 338 in 2010 to 8 054 in 2015. From 2010 to 2015, newly
      identified HIV cases in each year were 59, 166, 312, 283, 291, and 270, which
      accounted for 25.0%, 32.8%, 38.8%, 35.1%, 30.5%, and 23.2% of MSM HIV cases of
      Guangzhou, respectively. Sentinel surveillance data showed that during the study
      period, 3 047 MSM were investigated, with 405, 400, 401, 633, 608, and 600 each
      year, respectively. The proportion of participants who had received any HIV
      intervention during the past year was 74.3%(301), 70.8%(283), 83.3%(334),
      85.0%(538), 69.1%(420), and 83.8%(503)each year, respectively(trend chi2=6.53,
      P=0.011). HIV testing done during the past year accounted for 44.0%(178),
      44.3%(177), 49.4%(198), 53.4%(338), 56.1%(341), and 60.2%(361)each year,
      respectively(trend chi2=40.83, P<0.001). Unprotected anal intercourse in the past
      6 months accounted for 59.3%(240), 62.0%(248), 56.6%(227), 57.0%(361),
      48.4%(294), and 43.7%(262)each year, respectively(trend chi2=42.21, P<0.001).
      Conclusion: The"Internet Plus"AIDS prevention services in this study represent a
      manner to enhance traditional HIV prevention strategies. We found these services
      to be effective in implementation of the national AIDS control and prevention
      strategy, especially for the expansion of intervention, testing, and case
      identification among high-risk populations.

PMID- 27686762
TI  - [Influence of sociocultural factors on HIV transmission among men who have sex
      with men: a qualitative study].
AB  - Objective: To understand how social and cultural factors influence sexual
      perceptions, sexual practices, and HIV transmission among men who have sex with
      men at selected sites in China. Methods: Qualitative methodology was used and
      face to face, semi-structured, in-depth interviews conducted from April 2013 to
      October 2015 in Sichuan, Jiangxi, Henan, Heilongjiang provinces and Chongqing
      municipality of China. Results: A total of 184 men who have sex with men
      participated in the interviews. Forty-eight originated from Henan Province, and
      12, 50, 47, and 27 from Jiangxi, Heilongjiang, Sichuan provinces and Chongqing
      municipality, respectively. A total of 122 participants(66.3%)were under 30 years
      of age, 111 were college graduates(61.3%), 140 were unmarried(76.5%), and 74 were
      HIV positive(40.2%). Among interviewees, 6%(11 MSM)were employed at
      nongovernmental organizations. The main findings revealed that: Owing to
      sociocultural influences and social norms, most homosexual men concealed their
      sexual orientation and married females so as to fulfill their family obligation;
      this may encourage HIV transmission from a high-risk population to the general
      population; the main features of male homosexual behaviors, as well as those of
      the associated community and subculture, included hedonism, less concern about
      health, drug abuse, encouraging of high risk behaviors among men who have sex
      with men, and negative attitudes regarding HIV prevention; subgroups among MSM
      were found to have differential HIV transmission risk behaviors, with young men
      more vulnerable to infection with HIV. Conclusion: Sociocultural factors,
      including external socioenvironmental circumstances and internal MSM community
      subcultures, have adverse impacts on HIV transmission among men who have sex with
      men. Because there were varied behavior modes and HIV transmission risks among
      MSM subgroups, further study focusing on MSM subgroups is imperative, to provide
      a basis for more targeted and effective prevention strategies.

PMID- 27686763
TI  - [Features and influencing factors of self-discrimination among HIV/AIDS patients
      according to sex].
AB  - Objective: To investigate the features and influencing factors of self
      discrimination among patients with HIV/AIDS according to sex. Methods: A total of
      2 432 HIV/AIDS patients were recruited in Yunnan, Henan, Hubei, Jiangsu, Shanxi,
      Jilin, and Inner Mongolia provinces by a multistage stratified cluster sampling
      method, based on HIV epidemic and transmission modes, from May 2013 to October
      2013. All participants were >=18 years old, and we excluded those with mental
      disorders, hearing loss or other factors that prevented them from properly
      answering questions, and those who were unwilling to participate. A self-designed
      questionnaire was conducted to collect information about self-discrimination
      features and social behavior changes among HIV/AIDS patients. Differences in
      performance and self-discrimination features between participants of different
      sexes were compared using the chi-squared test. Factors influencing self
      discrimination were analyzed by sex, using unconditional logistic regression.
      Results: Of the 2 432 cases, 78.9%(1 918 cases)were male and 21.1%(514
      cases)female. The proportion of self-discrimination overall was 76.1%(1 850
      cases); this proportion among female HIV/AIDS patients was 80.5%(414 cases),
      which was higher than that among men(74.9%, 1 436 cases)(chi2=7.17, P=0.007). Of
      the 11 forms of self-discrimination performance, proportions of feeling guilt,
      shame, and self-abasement among participants were greater than 50%. Proportions
      of feeling shame, inferiority, and blaming others among females were 61.3%,
      59.5%, and 45.3%, respectively, which were higher than these among males(49.8%,
      50.0%, 28.4%, respectively)(P<0.01). Multivariate unconditional logistic
      regression analysis showed that the risk of self-discrimination among those with
      HIV confirmatory testing time >=1 year was higher than those with HIV
      confirmatory testing time <1 year(females: OR=35.67, 95%CI:17.28-73.64; males:
      OR=8.74, 95% CI:6.79-11.25). Compared with other occupations, the risk of self
      discrimination among male farm workers was higher(OR=1.62, 95% CI:1.03-2.54). The
      risks of self-discrimination in males who had been infected with HIV by
      transmission routes of blood transfusion or blood collection(OR=2.38, 95% CI:1.31
      4.30), injection drug use(OR=1.78, 95% CI:1.09-2.91), and male-to-male sexual
      behavior(OR=1.48, 95%CI:1.08-2.03)were higher than in males infected via
      heterosexual behavior. Conclusion: Female HIV/AIDS patients are more likely to
      engage in self-discrimination than male patients. Self-discrimination mainly
      takes the form of feeling remorse, shame, and inferiority. Confirmatory testing
      time >=1 year, occupation as a farm work, and routes of transmission via blood
      transfusion or collection, injection drug use, and male-to-male sexual behavior
      are influencing factors of self-discrimination among male HIV/AIDS patients.
      Confirmatory testing time >=1 year is the influencing factor of self
      discrimination among female HIV/AIDS patients.

PMID- 27686764
TI  - [Characterization of N-linked glycosylation sites on envelope proteins of
      simian/human immunodeficiency virus in peripheral blood of Chinese rhesus
      macaques during acute infection].
AB  - Objective: To investigate the number and distribution of N-linked glycosylation
      sites of simian/human immunodeficiency virus envelope proteins(SHIVSF162P3)and
      SHIV transmission. Methods: Two female adult Chinese rhesus macaques(4 years
      old)were intravenously inoculated with 300 TCID50 SHIVSF162P3. The macaques
      weighed 4 and 5 kg and were identified as Rh1 and Rh2. We collected plasma
      samples at days 3, 7, 10, 14, 17, 21, 24, 28, 35, 42, 49, 56, 63, 70 and 77 post
      challenge. Subsequently, we monitored plasma viral load by real-time PCR after
      viral RNA isolation and cDNA synthesis. We amplified the full-length envelope
      gene by single genome amplification(SGA)at days 7, 14, 28 and 77. BioEdit, MEGA,
      and the HIV Databases were used to analyze envelope sequences. Sequence diversity
      and N-linked glycosylation sites were compared between virus stock and plasma
      viruses of the two macaques. Results: A total of 55 env sequences were obtained
      from virus stock and their average pairwise distances were(0.166 6+/- 0.096 3)%.
      Viral loads peaked at 7.68 and 7.49 log10 copies/ml at day 10 and reached the set
      point at day 42(4.27 and 4.81 log10 copies/ml). The percentages of envelope
      sequences containing 25 potential N-linked glycosylation sites(PNGSs)were
      83%(20/24)and 94%(29/31)in Rh1 and Rh2, respectively, at day 7; these were
      significantly higher than the proportion in SHIVSF162P3 stock(49%(27/55)). Viral
      diversity after infection increased with time whereas the proportion of sequences
      containing 25 PNGSs decreased and sequences containing 27 PNGSs gradually
      increased. In Rh1, the percentage of sequences containing 27 PNGSs increased to
      29% at day 28 and reached 35% at day 77 in Rh2. By analyzing the number of PNGSs
      in the V1-V5 regions, we found that PNGS variation mainly occurred in the V4
      loop. Compared with sequences containing 27 PNGSs, a seven amino
      acid(TWNNTIG)deletion was found in the V4 loop, which resulted in a loss of two
      PNGSs at positions 392 and 396. Conclusion: Low glycosylation of the SHIVSF162P3
      V4 loop may facilitate spread of the SHIV virus whereas viruses with highly
      glycosylated V4 loops showed replication advantages after infection.

PMID- 27686765
TI  - [Impact of PM2.5 on daily outpatient numbers for respiratory diseases in
      Shenzhen, China].
AB  - Objective: To assess the association between the concentration of the air
      pollutant PM2.5 and daily outpatient visits for respiratory disease. Methods: All
      records of daily outpatient visits to three hospitals in Shenzhen from January 1
      to December 31, 2013 were collected. Daily air pollution monitoring and
      meteorology data from the same period were also collected in Shenzhen. The data
      were analyzed using a semiparametric generalized additive model with Poisson
      distribution of time series analysis controlling for long-term and seasonal
      trends, flu, DOW, public holidays, and meteorological factors. The excess
      risk(ER)of respiratory disease and its 95% CI value were calculated, along with
      the incremental increase of 10 MUg/m3 in PM2.5 concentration. Results: Number of
      outpatient visits for respiratory diseases totaled 1 428 672(daily range: 1 790-5
      228). The annual average PM2.5 concentration was 40.2 MUg/m3(daily range: 7.2
      137.1 MUg/m3). The lag1 factor had the most significant impact on the lag effect.
      We estimated that a 10 MU g/m3 increase in day-before PM2.5 concentration was
      associated with a 1.809%(95% CI: 1.709%-1.909%)ER of visits for respiratory
      disease. After controlling for other pollutants(NO2, CO, and O3), the effect
      remained stable. When NO2, CO, and O3 were introduced separately, for every 10
      MUg/m3 rise in PM2.5 concentration, the excess risk of daily outpatient visits
      for respiratory disease was 1.814%(95% CI: 1.706%-1.923%), 2.780%(95% CI: 2.668%
      2.892%), and 1.513%(95% CI: 1.403%-1.624%), respectively. With simultaneous
      control of NO2 and O3, NO2 and CO, and CO and O3, for every 10 MUg/m3 rise in
      PM2.5 concentration, the excess risk of respiratory disease was 1.369%(95% CI:
      1.242%-1.497%), 2.709%(95% CI: 2.590%-2.828%), and 2.577%(95% CI: 2.452%-2.702%),
      respectively. With simultaneous control of NO2, CO, and O3, for every 10 MUg/m3
      rise in PM2.5 concentration, the excess risk of respiratory disease was
      2.370%(95% CI: 2.231%-2.509%). Conclusions: PM2.5 can increase the risk of
      outpatient visits for respiratory disease in Shenzhen.

PMID- 27686766
TI  - [Study of survival factors of oral squamous cell carcinoma].
AB  - Objective: To explore the survival factors for oral squamous cell
      carcinoma(OSCC). Methods: A total of 492 patients with OSCC were recruited from
      the First Affiliated Hospital of Fujian Medical University from June 2003 to
      December 2014. Then, 456 cases were included in the present study according to
      inclusion and exclusion criteria. Clinical and follow-up data were collected to
      evaluate survival factors of OSCC. Survival rates were calculated using the
      Kaplan-Meier method and compared using the Log-rank test. The Cox proportional
      hazards regression model was used to estimate the hazard ratio(HR)and 95%
      confidence intervals(CI)of survival factors. We also stratified by TNM
      Classification of Malignant Tumours stage and BMI to assess the association
      between treatments and OSCC outcomes. Results: The age of the recruited patients
      was(57.89+/-11.61)years, and the proportions in TNM stages I, II, III, and IV
      were 14.0%(64), 23.7%(108), 16.1%(73)and 42.5%(194), respectively. The
      multivariate Cox regression indicated that the HR(95% CI)of the increase to
      mortality risk associated with stage T2-T3, T4(T1 as reference), stage N2-N3(N0
      as reference), poormoderate differentiation, BMI<18.5 kg/m2(compared with BMI
      18.5-23.9 kg/m2), alcohol consumption >=20 g/d(compared with no alcohol)before
      treatment were 2.69(1.21-5.95), 3.40(1.54-7.53), 2.65(1.17-6.00), 2.56(1.39
      4.71), 2.00(1.15-3.50), 2.09(1.11-3.93), and 1.68(1.03-2.73), respectively. The
      stratification analysis demonstrated that, compared with surgery alone, surgery
      combined with radiotherapy reduced the mortality risk of stage III-IV, HR(95%
      CI)0.33(0.12-0.93). Surgery combined with chemoradiotherapy reduced the mortality
      risk of OSCC with normal BMI, HR(95% CI)were 0.39(0.17-0.87). Conclusions:
      Clinical stage and histological grade are survival factors for patients with
      OSCC.

PMID- 27686767
TI  - [Analysis for the breast cancer screening among urban populations in China, 2012
      2013].
AB  - Objective: To analyze results of breast cancer screenings in the Cancer Screening
      Program in Urban China(CanSPUC)during 2012-2013. Methods: In 14 cities of 9
      provinces(Eastern Region: Beijing, Hebei, Liaoning, Shandong and Guangdong;
      Central Region: Heilongjiang and Hunan; Western Region: Chongqing and Gansu), 198
      097 women aged 40-69 years who had lived in their cities for >=3 years were
      surveyed through a cancer risk assessment questionnaire during 2012-2013. The
      questionnaires identified women considered to be at high risk for breast cancer,
      of whom 17 104 received screening examinations, for whom complete records of
      breast cancer screening and other data were available for 12 440 subjects
      altogether, including breast ultrasound exams for subjects 40-44 years old.
      Subjects older than 45 years or in whom breast imaging reporting and data
      system(BI-RADS)ultrasound had found >= 3 lesions also underwent mammography. In
      this cohort, BI-RADS 3 class was defined as suspicious and BI-RADS >=4 class as
      positive. Chi-square tests were used to compare breast cancer screening results
      by groups. Results: As of October 2013, breast cancer screening percentages for
      the 12 440 subjects for whom full data were available were, by region, Eastern:
      55.43%(6 895); Central: 21.45%(2 669); and Western: 23.12%(2 876); by age, 40-44
      years: 5.50%(684); >=45 years: 94.50%(11 756). Using BI-RADS, 2018 subjects were
      found to have 3 lesions(detection rate: 16.22%), which were distributed
      regionally as Eastern: 19.00%(1 310 women), Central: 13.75%(367)and Western;
      11.86%(341); chi2=91.45, P<0.001; and 289 were found to have >=4
      lesions(detection rate: 2.32%), which were distributed regionally as Eastern:
      2.41%(166), Central: 1.54%(41)and Western; 2.85%(82); chi2=11.04, P=0.004. Women
      aged 50-54 years had the highest detection rate of BI-RADS 3 lesions at
      18.74%(561/2 994), and those aged 40-44 years had the highest detection rate of
      BI-RADS >=4 at 2.92%(20/684). Conclusion: Detection rates of BI-RADS >=4 lesions
      were highest in the Western region and in women aged 40-44 years, and lowest in
      the Central region and in women aged 60-64 years. Detection rates of BI-RADS 3
      lesions were highest in the Eastern region and in women aged 50-54 years and the
      lowest in the Western region and in women aged 60-64 years.

PMID- 27686768
TI  - [Association of exposure to environmental chemicals with risk of childhood acute
      lymphocytic leukemia].
AB  - Objective: This study aimed to investigate the association between exposure to
      environmental chemicals and the risk of childhood acute lymphocytic
      leukemia(cALL). Methods: A case-controlled study was conducted in Shenzhen
      Children's Hospital, China from January 2015 to January 2016. The cases were
      selected from the section of Hematology and Oncology, and the controls were
      selected from Orthopedics by 1?2 matching of cases according to sex and age. A
      questionnaire including population data and chemical exposure characteristics was
      conducted on the children's parents, and urine and EDTA-blood were collected from
      the children. Then, we quantitatively measured the internal dose of
      formaldehyde(i.e., formaldehyde-human serum albumin)by enzyme-linked
      immunosorbent assay and the doses of metabolites benzene, toluene, and
      xylene(i.e., trans-muconic acid, hippuric acid, and methylhippuric acid)by high
      performance liquid chromatography. Logistic regression models were used to
      analyze the relationships between exposure factors measured from children and
      their parents and cALL. Results: In the study, 71 cases(average age: 6.08+/-3.61
      years), and 142 controls(average age: 5.91+/-3.57 years)were assessed; there were
      no differences in general demographics between two groups. The self-reported
      results showed that living in a home that had been painted in the past 10
      years(OR=4.39, 95% CI: 1.87-10.31), maternal chemical exposure during
      pregnancy(OR=11.78, 95% CI: 1.65-83.88), paternal diesel or gasoline
      exposure(OR=8.15, 95% CI: 2.68-24.83), paternal dye exposure(OR=7.77, 95% CI:
      1.52-39.67)and trash burning near the child's residence(OR=6.08, 95% CI: 1.17
      31.66)were associated with increased risk of cALL. The positive detection rates
      of only benzene metabolites were significantly higher in cases(40/44)than
      controls(81/111)(chi2=5.92, P=0.021). The median formaldehyde and benzene
      concentrations in cases(32.120 pg/ml, 2.505 MUg/gCr)were significantly higher
      than those in controls(18.705 pg/ml, 0.672 MUg/gCr; Z values:-1.98 and-3.95, P
      values: 0.047 and<0.001, respectively). Multiple logistic regression analysis
      showed that benzene exposure(OR=1.09, 95% CI: 1.00-1.19), home painting in the
      past 10 years(OR=3.56, 95% CI: 1.20-10.53)and paternal diesel or gasoline
      exposure(OR= 3.75, 95% CI: 1.06-13.22)were associated with increased risk of
      cALL. Conclusion: A variety of environmental chemistry factors, such as benzene
      exposure, increase the risk of cALL, and further studies are warranted to explore
      their specific roles.

PMID- 27686769
TI  - [Association and interaction of heat shock proteins B1 gene and tumor-suppressor
      protein p53 gene with chromosome damage levels among coke oven workers].
AB  - Objective: To investigate the association and interaction of heat shock proteins
      B1(HSPB1)gene rs2868371 and tumor-suppressor protein p53(TP53)gene rs1042522
      polymorphisms with chromosome damage levels among coke oven workers. Methods: We
      recruited 1 333 male workers from a state-run coke oven plant in Wuhan in
      September-October 2010. Among them, 949 who had worked in coke oven workplaces,
      including auxiliary facilities and bottom, side, and top ovens, were nominated as
      coke oven workers(i.e., exposed), and 384 administrative or medical staff whose
      workplaces were offices were used as controls. General characteristics and 5 ml
      of venous blood were collected from each participant. The plasma concentrations
      of benzo[a]pyrene-diolepoxide(BPDE)-albumin adducts and the lymphocytic
      micronucleus(MN)frequencies for each individual were detected by ELISA and
      cytokinesis-block micronucleus assay, respectively. Gene polymorphisms were
      genotyped using TaqMan assays via quantitative PCR(ABI Prism 7900HT), and the
      corresponding frequency ratios(FR)with 95% confidence intervals(CI)were computed
      for all assays. Results: In the exposed group, the MN frequencies were higher in
      HSPB1 rs2868371 GC, CC, and GC+ CC genotype carriers((3.88 +/- 2.88)0/00,(4.00 +/
      2.66)0/00, and(3.91 +/- 2.83)0/00, respectively)than in rs2868371 GG genotype
      carriers((3.52+/-2.67)0/00; FR=1.10, 1.13, and 1.11; 95% CI: 1.02-1.19, 1.02
      1.25, and 1.03-1.19, respectively), and the HSPB1 rs2868371C allele was
      associated with increased MN frequency(Ptrend=0.006). Further, in the exposed
      group, the MN frequencies were lower in TP53 rs1042522 CG and CG+GG genotype
      carriers((3.63+/-2.61)0/00 and(3.66+/-2.61)0/00, respectively)than in TP53
      rs1042522 CC genotype carriers(3.95+/-3.06)0/00(FR=0.87 and 0.90; 95% CI: 0.83
      0.96 and 0.84-0.97, respectively). The effect of gene-gene interaction between
      HSPB1, rs2868371, and TP53 rs1042522 on MN frequency was significant among coke
      oven workers(P=0.001). Further stratified analyses showed that the effects of the
      HSPB1 rs2868371C allele in increasing MN frequencies were robust in subjects aged
      >40 years(FR=1.07, 95% CI: 1.01-1.12), those working >20 years(FR=1.08, 95% CI:
      1.02-1.14), those with BMI <=24 kg/m2(FR=1.07, 95% CI: 1.01-1.13),
      drinkers(FR=1.09, 95% CI: 1.02-1.16), and workers with higher BPDE-albumin adduct
      levels(FR=1.07, 95% CI: 1.01-1.13)(Ptrend=0.023, 0.013, 0.029, and 0.020,
      respectively). The decreasing effect of the TP53 rs1042522 G allele on MN
      frequencies was robust in subjects aged >40 years(FR=0.94, 95% CI: 0.89-0.99),
      those with BMI <=24 kg/m2(FR=0.94, 95% CI: 0.88-0.99), and drinkers(FR=0.94, 95%
      CI: 0.88-1.00)(Ptrend=0.031, 0.023, and 0.038, respectively). In addition, there
      were interactions between HSPB1 rs2868371 and age and between HSPB1 rs2868371 and
      working years in terms of MN frequency(P=0.030 and 0.013, respectively).
      Conclusion: In coke oven workers, the HSPB1 rs2868371 C and TP53 rs1042522 G
      alleles were associated with increased and decreased chromosome damage levels,
      respectively, and their interaction effect on chromosome damage levels was
      significant.

PMID- 27686770
TI  - [Survey on fungi contamination and natural occurrence of mycotoxins in 94 corn
      feed ingredients collected from China].
AB  - Objective: To investigate fungi contamination and the natural occurrence of
      mycotoxins in corn feed ingredients collected from China. Methods: A total of 94
      corn feed ingredient samples were collected from 8 Chinese provinces(i.e., Anhui,
      Hebei, Heilongjiang, Jilin, Jiangsu, Liaoning, Inner Mongolia, and Shandong)in
      February 2014. A tandem ultra-performance liquid chromatographymass spectrometry
      method was used for simultaneous detection of twelve kinds of mycotoxins,
      including aflatoxin(AF), type A and type B tricothecenes, and zearalenone(ZEN).
      Contaminated fungi were also identified and counted. Results: AF was detected in
      36.2%(34/94)of samples; the concentration of AFB1 was the highest in the four AFs
      with the range: 0.3~181.3 MUg/kg; and then followed by AFB2(range: 1.0-74.3
      MUg/kg). There were 7 samples(7.5%)with AFB1 concentrations higher than the
      tolerance limit of 50 MUg/kg. The concentration of type A tricothecenes in all
      samples was lower(0.1-10.5 MUg/kg). DON had the most serious contamination than
      other kind of type B tricothecenes(range: 0.7-606.6 MUg/kg; median: 66.3 MUg/kg).
      The DON concentration in all samples was below the tolerance limit of 1 000
      MUg/kg. ZEN was detected in 76.6%(72/ 94)of samples(median: 36.9 MUg/kg), with 3
      samples having ZEN concentrations higher than the tolerance limit of 500 MUg/kg.
      The survey on fungi contamination showed that all samples were contaminated by
      fungi(range: 5.0-1.4*105 CFU/g). There were 18 and 3 samples with quantities of
      fungi higher than the tolerance and forbidden limits, respectively. The
      Aspergillus, Penicillium, Fusarium, Trichoderma and Mucor genuses were the
      predominant fungi in corn feed ingredients, with detection rates of 71.3%(67),
      60.6%(57), 71.3%(67), 27.7%(26), and 24.5%(23), respectively. The detection rate
      of Fusarium moniliforme, 73.4%(69/94)was higher than that of Aspergillus flavus,
      41.5%(39/94). Conclusion: In this survey, the corn feed ingredients were not
      seriously contaminated by AF and type A tricothecenes but mainly contaminated by
      type B trichothecenes, including DON and its derivatives, as well as ZEN. They
      were also contaminated by fungi such as Aspergillus, Penicillium, and Fusarium.

PMID- 27686771
TI  - [Dietary patterns and the risk of cardiovascular disease mortality: A nested case
      control study].

PMID- 27686772
TI  - [Comparative analysis of air quality in 31 cities between 2014 and 2015, China].

PMID- 27686773
TI  - [To explore "the trinity(center for disease control-hospital-community)" of
      HIV/AIDS control and prevention model].

PMID- 27686774
TI  - [The exploration of the effectiveness of the combination model between AIDS
      prevention and basic public health services].

PMID- 27686775
TI  - [Advance research on association between environmental compound and parkinson's
      disease].
AB  - Parkinson's disease(PD)was the second most common neurodegenerative disorder
      after Alzheimer's disease. Incidence of PD was ascending year by year. The
      etiology of PD is poorly understood, involving aging, genetic and environmental
      factors. Recently, environmental compound had attracted more and more research
      interest. Studies and extrapolation from epidemiology, animal experiments and
      cell culture suggested that environmental compound had involved in the molecular
      mechanisms including mitochondrial dysfunction, oxidative stress, microglia
      activation, abnormal aggregation of alpha-synuclein and autophagy damage ,which
      seemed to increase PD risk.

PMID- 27686776
TI  - [Huazhong cohort of common and chronic non-communicable diseases].

PMID- 27686777
TI  - [Research of integration techniques of national biosecurity surveillance
      network].

PMID- 27686778
TI  - Folliculitis in prurigo pigmentosa: a proposed pathogenesis based on clinical and
      pathological observation.
AB  - BACKGROUND: Prurigo pigmentosa is a rare inflammatory dermatosis whose exact
      etiology is not understood yet. The purpose of this study was to provide evidence
      of hair follicle involvement in the pathogenesis by analyzing its
      clinicopathologic features. METHODS: Patients who fulfilled both the clinical and
      histological diagnostic criteria of prurigo pigmentosa were recruited. Their
      histopathologic findings, clinical features and medical histories were analyzed.
      RESULTS: A total of 32 confirmed patients were enrolled from 2002 to 2013. Their
      ages ranged from 11 to 79 years with a female predominance. Patient lesions were
      primarily reddish-brown and located on the back. A total of 25 patients (78%) had
      pathological involvement of hair follicles, either bacterial colonies in the hair
      follicles (21/32, 66%), folliculitis (8/32, 25%) or perifolliculitis (15/32,
      47%). There was a significantly higher proportion of patients with hair follicle
      involvement compared with control groups with either noninflammatory (5/43, 12%,
      p < 0.001) or inflammatory skin diseases (12/32, 38%, p = 0.002) on the back.
      Minocycline was an effective antibiotic treatment either singly or in combination
      with steroids. CONCLUSIONS: The frequent presence of bacterial colonies along
      with sequelae of inflammatory changes on biopsy provides new evidence to support
      the theory that prurigo pigmentosa is a reactive inflammation associated with
      bacterial folliculitis.

PMID- 27686779
TI  - Concentrating Emergency Rooms: Penny-Wise and Pound-Foolish? An Empirical
      Research on Scale Economies and Chain Economies in Emergency Rooms in Dutch
      Hospitals.
AB  - In this paper, we address the issue of whether it is economically advantageous to
      concentrate emergency rooms (ERs) in large hospitals. Besides identifying
      economies of scale of ERs, we also focus on chain economies. The latter term
      refers to the effects on a hospital's costs of ER patients who also need follow
      up inpatient or outpatient hospital care. We show that, for each service
      examined, product-specific economies of scale prevail indicating that it would be
      beneficial for hospitals to increase ER services. However, this seems to be
      inconsistent with the overall diseconomies of scale for the hospital as a whole.
      This intuitively contradictory result is indicated as the economies of scale
      paradox. This scale paradox also explains why, in general, hospitals are too
      large. There are internal (departmental) pressures to expand certain services,
      such as ER, in order to benefit from the product-specific economies of scale.
      However, the financial burden of this expansion is borne by the hospital as a
      whole. The policy implications of the results are that concentrating ERs seems to
      be advantageous from a product-specific perspective, but is far less advantageous
      from the hospital perspective. (c) 2016 The Authors. Health Economics Published
      by John Wiley & Sons, Ltd.

PMID- 27686780
TI  - Evaluation of a Clinical Cancer Trial Research Training Workshop: Helping Nurses
      Build Capacity in Southwest Virginia.
AB  - Residents of Southwest Virginia (SWVA) face significant barriers in accessing the
      most advanced forms of cancer care, cancer risk reduction, and clinical trials
      involvement. A collaboration between the University of Virginia (UVA) Cancer
      Center and UVA School of Nursing was forged with oncology caregivers in this
      region to build community capacity to support Cancer Clinical trials (CCT) by
      strengthening the workforce, and thus improving health outcomes for this
      underserved region of Appalachia. The UVA School of Nursing designed an
      educational workshop focusing on the basics of CCT to facilitate the development
      of a skilled nursing workforce in the SWVA region that could provide care to
      patients on protocol and/or to encourage residents to participate in trials. The
      goal of the workshop was to offer a CCT training session for oncology nurses that
      fostered the knowledge and skills necessary to facilitate and support CCT
      infrastructure across this high-risk region. This evaluation reports the learning
      outcomes of the CCT training on 32 nurse participants from SWVA. Evaluations of
      the training program showed high rates of satisfaction, increased comfort level
      with CCTs, and increased knowledge and attitude toward CCTs. These findings
      provide information about a curriculum that could be useful in educating other
      oncology nurses and student nurses how to care for patients who may be enrolled
      in a clinical trial. Nurses can also be advocates for participation in clinical
      trials once they have the knowledge and are comfortable in their own
      understanding of a trial's usefulness. Educating the nursing workforce is an
      essential component of building capacity and infrastructure to support clinical
      trials research.

PMID- 27686781
TI  - Determinants of Potentially Inappropriate Medication Use among Community-Dwelling
      Older Adults.
AB  - OBJECTIVE: To examine the determinants of potentially inappropriate medication
      (PIM) use. DATA SOURCES/STUDY SETTING: U.S. nationally representative data on (n
      = 16,588) noninstitutionalized older adults (age >=65) with drug use from the
      2006-2010 Medical Expenditure Panel Survey. STUDY DESIGN: We operationalized the
      2012 Beers Criteria to identify PIM use during the year, and we examined
      associations with individual-level characteristics hypothesized to be quality
      enabling or related to need complexity. PRINCIPAL FINDINGS: Almost one-third
      (30.9 percent) of older adults used a PIM. Multivariate results suggest that poor
      health status and high-PIM-risk conditions were associated with increased PIM
      use, while increasing age and educational attainment were associated with lower
      PIM use. Contrary to expectations, lack of a usual care source of care or
      supplemental insurance was associated with lower PIM use. Medication intensity
      appears to be in the pathway between both quality-enabling and need-complexity
      characteristics and PIM use. CONCLUSION: Our results suggest that physicians
      attempt to avoid PIM use in the oldest old but have inadequate focus on the high
      PIM-risk conditions. Educational programs targeted to physician practice
      regarding high-PIM-risk conditions and patient literacy regarding medication use
      are potential responses.

PMID- 27686782
TI  - An Overview of Treatment Methods for Primary Angle Closure.
AB  - BACKGROUND: Glaucoma is the second leading cause of blindness in the world. Angle
      closure glaucoma accounts for 25% of all glaucoma, with Asia having the highest
      rate. Angle closure is an anatomical variation, making the Inuit, Chinese, and
      other Asians more susceptible. Current treatments include medical, laser, and
      surgical modalities. PURPOSE: To identify the current treatment protocols for
      primary angle closure. DISCUSSION: The current general protocol to treat angle
      closure is to lower the intraocular pressure with medications and perform laser
      iridotomy. However, cataract surgery, laser iridoplasty, goniosynechiolysis,
      diode cyclophotocoagulation, and filtering surgery are additional treatment
      modalities used for primary angle closure. CONCLUSION: Primary angle closure
      occurs due to various anatomical angle variations. Laser iridotomy is not the
      sole method of treatment. Specifically, cataract surgery can be particularly
      effective in the treatment and prevention of angle closure. Recalcitrant cases
      can be treated with trabeculectomy and shunt implants, although these are not
      usually first-line treatments.

PMID- 27686783
TI  - New challenge for bionics--brain-inspired computing.

PMID- 27686785
TI  - Concept of scientific wildlife conservation and its dissemination.
AB  - In recent years, wildlife conservation has attracted great public attention.
      However, substantial distinctions can be found in the prevailing concepts of
      wildlife conservation, particularly with the recent notion that emphasizes animal
      rights. Wildlife welfare and wildlife rights are not synonymous, with welfare
      more compatible with the reasonable and legal utilization of wildlife. The key to
      scientific wildlife conservation is the appropriate awareness and appreciation of
      the relationship between wildlife conservation and utilization and the
      theoretical basis of holism. Nevertheless, rational biases regarding the public's
      understanding of wildlife conservation and the spread of information via social
      media still exist. As such, expansion of the concept of scientific wildlife
      conservation requires the application of several measures. Wildlife conservation
      researchers should be regarded as the most important disseminators of
      scientifically-based information, with education in schools and universities of
      growing importance. Furthermore, the media should shoulder the social
      responsibility for the accurate dissemination of conservation information. 

PMID- 27686784
TI  - Lamprey: a model for vertebrate evolutionary research.
AB  - Lampreys belong to the superclass Cyclostomata and represent the most ancient
      group of vertebrates. Existing for over 360 million years, they are known as
      living fossils due to their many evolutionally conserved features. They are not
      only a keystone species for studying the origin and evolution of vertebrates, but
      also one of the best models for researching vertebrate embryonic development and
      organ differentiation. From the perspective of genetic information, the lamprey
      genome remains primitive compared with that of other higher vertebrates, and
      possesses abundant functional genes. Through scientific and technological
      progress, scientists have conducted in-depth studies on the nervous, endocrine,
      and immune systems of lampreys. Such research has significance for understanding
      and revealing the origin and evolution of vertebrates, and could contribute to a
      greater understanding of human diseases and treatments. This review presents the
      current progress and significance of lamprey research. 

PMID- 27686786
TI  - What is the destiny of a threatened fish, Ptychobarbus chungtienensis, now that
      non-native weatherfishes have been introduced into Bita Lake, Shangri-La?
AB  - Biological invasion is a pervasive negative force of global change, especially in
      its effects on sensitive freshwater ecosystems. Even protected areas are usually
      not immune. Ptychobarbus chungtienensis is a threatened freshwater fish now
      almost confined to Bita Lake, in the Shangri-La region of Yunnan province, China.
      Its existence is threatened by the introduction of non-native weatherfishes
      (Misgurnus anguillicaudatus and Paramisgurnus dabryanus) by an unusual method
      known as 'prayer animal release'. Periodic surveys revealed the ratio of invasive
      weatherfishes to P. chungtienensis has been increasing since the former species
      was first recorded from the lake in August, 2009. Ptychobarbus chungtienensis
      shows low genetic diversity in the relict Lake Bita population. Weatherfishes,
      however, have highly successful survival strategies. The degree of dietary
      overlap between the species is alarming and perhaps critical if food is found to
      be a limiting factor. 

PMID- 27686788
TI  - A new species of the genus Triplophysa (Cypriniformes: Nemacheilidae),
      Triplophysa daochengensis, from Sichuan Province, China.
AB  - Triplophysa daochengensis sp. nov. is described from the Daocheng River, a
      northern tributary of the Jinsha River in Sichuan Province, China. The new
      species can be distinguished from its congeners by the following characters: body
      smooth and scales absent; lateral line complete; caudal peduncle compressed,
      depth unchanging; head length equal to caudal-peduncle length; lower jaw shovel
      shaped; dorsal-fin origin anterior to pelvic-fin origin and closer to the tip of
      the snout than to the caudal-fin base, last unbranched ray hard; pelvic-fin tip
      not reaching anus; posterior chamber of gas bladder absent; intestine of spiral
      type with three winding coils. 

PMID- 27686787
TI  - Evolution and phylogenetic application of the MC1R gene in the Cobitoidea
      (Teleostei: Cypriniformes).
AB  - Fish of the superfamily Cobitoidea sensu stricto (namely loaches) exhibit
      extremely high diversity of color patterns, but so far little is known about
      their evolutionary mechanism. Melanocortin 1 receptor gene (MC1R) plays an
      important role during the synthesis of melanin and formation of animal body color
      patterns. In this study, we amplified and sequenced the partial MC1R gene for 44
      loach individuals representing 31 species of four families. Phylogenetic analyses
      yielded a topology congruent with previous studies using multiple nuclear loci,
      showing that each of the four families was monophyletic with sister relationships
      of Botiidae+ (Cobitidae+(Balitoridae+Nemacheilidae)). Gene evolutionary analyses
      indicated that MC1R in loaches was under purifying selection pressure, with
      various sites having different dN/dS values. Both Botiidae and Cobitidae had
      lower dN/dS values than those of background lineages, suggesting their evolution
      might be strongly affected by purifying selection pressure. For Balitoridae and
      Nemacheilidae, both had larger dN/dS values than those of background lineages,
      suggesting they had a faster evolutionary rate under more relaxed selection
      pressure. Consequently, we inferred that the relatively stable color patterns in
      Botiidae and Cobitidae might result from the strong purifying selection pressure
      on the MC1R gene, whereas the complicated and diverse color patterns in
      Balitoridae and Nemacheilidae might be associated with the relaxed selection
      pressure. Given the easy experimental procedure for the partial MC1R gene and its
      excellent performance in reconstructing phylogeny, we suggest this gene could be
      used as a good molecular marker for the phylogenetic study of fish species. 

PMID- 27686789
TI  - A new cave species of the Genus Triplophysa from Yunnan, China.
AB  - In September and October 2015, a new species of the family Nemacheilidae,
      Triplophysa tianxingensis sp. nov., was discovered from underground water in
      Qiubei County, Yunnan Province, China. It can be distinguished from all other
      troglobiotic Triplophysa species occurring in Yunnan by the following combination
      of characters: eyes small, a little degenerated; barbels longer; ventral profiles
      greatly convex; pectoral fin short, attaining a third of the distance from the
      pectoral-fin base to pelvic fin base; body with many brown blotches; caudal
      peduncle with fin fold; caudal fin shallowly forked, and free posterior chamber
      of swim bladder cylindrical. 

PMID- 27686790
TI  - Identification of candidate piRNAs in the gonads of Paralichthys olivaceus
      (Japanese flounder).
AB  - Piwi-interacting RNA (piRNA) plays an important role in the gonadal development
      and maintenance of Teleostei. In this study, piRNA libraries derived from the
      adult gonads of Japanese flounder (Paralichthys olivaceus) were generated using
      next-generation sequencing technology. Using zebrafish piRNAs as a reference, 5
      865 unique candidate piRNAs were identified; 289 candidate piRNA clusters (PRCs)
      were generated from the above piRNAs. Among the isolated candidate PRCs, a total
      of 38 ovary-specific, 45 ovary-bias, 24 testis-specific, and 131 testis-bias PRCs
      were found. The relative expression levels of seven PRCs were validated through
      quantitative reverse transcription-polymerase chain reaction. The results of this
      study will help facilitate exploration of the development and maintenance of the
      phenotypic sex mechanism in P. olivaceus. 

PMID- 27686791
TI  - Identification of Sphaeroma terebrans via morphology and the mitochondrial
      cytochrome c oxidase subunit I (COI) gene.
AB  - Sphaeroma terebrans, a wood-boring isopoda, is distributed worldwide in tropical
      and subtropical mangroves. The taxonomy of S. terebrans is usually based on
      morphological characteristics, with its molecular identification still poorly
      understood. The number of teeth on the uropodal exopod and the length of the
      propodus of the seventh pereopod are considered as the major morphological
      characteristics in S. terebrans, which can cause difficulty in regards to
      accurate identification. In this study, we identified S. terebrans via molecular
      and morphological data. Furthermore, the validity of the mitochondrial cytochrome
      c oxidase subunit I (COI) gene as a DNA barcode for the identification of genus
      Sphaeroma, including species S. terebrans, S. retrolaeve, and S. serratum, was
      examined. The mitochondrial COI gene sequences of all specimens were sequenced
      and analysed. The interspecific Kimura 2-parameter distances were higher than
      intraspecific distances and no intraspecific-interspecific distance overlaps were
      observed. In addition, genetic distance and nucleotide diversity (pi) exhibited
      no differences within S. terebrans. Our results revealed that the mitochondrial
      COI gene can serve as a valid DNA barcode for the identification of S. terebrans.
      Furthermore, the number of teeth on the uropodal exopod and the length of the
      propodus of the seventh pereopod were found to be unreliable taxonomic
      characteristics for S. terebrans. 

PMID- 27686792
TI  - Authorship misconduct.

PMID- 27686793
TI  - Eradication of Helicobacter spp. in mucin2-deficient mice.
AB  - Infections with Helicobacter spp. are known to have serious effects on rodent
      health, especially in immunocompromised animals. In this study three approaches
      were used to eradicate Helicobacter spp. infection in mice with a deficiency in
      intestinal proteoglycan (mucin2), namely triple oral antibiotic therapy
      (amoxicillin, clarithromycin and metronidazole), cross-fostering of neonatal pups
      by surrogate mothers negative for Helicobacter spp., and in vitro fertilization
      (IVF) with embryo transfer into Helicobacter-free mothers. However, triple
      antibiotic therapy in mice with mucin2 deficiency was not effective and had
      negative effects on reproductive performance, and high susceptibility of mucin2
      deficient mice to Helicobacter spp. during the first 12 h after birth rendered
      cross-fostering impossible. Only IVF with embryo transfer was effective in
      eradicating Helicobacter infection from transgenic mice with mucin2 deficiency.

PMID- 27686794
TI  - Post-trabeculectomy ocular biometric changes.
AB  - Trabeculectomy is the most common surgical procedure for the management of
      glaucoma, which may significantly influence ocular biometry. Axial length and
      anterior chamber depth tend to decrease, while crystalline lens and choroidal
      thickness increase post-operatively. An increase in with-the-rule astigmatism is
      also observed after the procedure. Such biometric changes affect intraocular lens
      power calculation even years after the procedure. Non-contact biometric methods
      and postponing cataract surgery after trabeculectomy could reduce calculation
      errors associated with surgically induced alterations in ocular biometrics.

PMID- 27686795
TI  - Emerging treatments for severe obesity in children and adolescents.
AB  - Severe obesity in childhood is increasing in prevalence and is associated with
      considerable morbidity. Studies into pediatric obesity have focused largely on
      interventions that do not necessarily target the unique biologic or psychological
      underpinnings for the weight gain in the individual child or adolescent. Outcomes
      show modest improvement and are of questionable benefit for patients with severe
      obesity. Although weight is a commonly used outcome, other psychological and
      metabolic parameters including normalization of physical activity and eating
      behaviors should be primary outcome goals. The durability of weight loss is often
      limited by physiologic systems that are evolutionarily designed to promote weight
      gain. Drug therapies for children are limited, as is their effect on weight and
      metabolism. Existing drugs that are incidentally found to cause weight loss
      through off-target effects are being actively investigated for obesity
      indications. Bariatric surgery results in the most significant weight reduction,
      but it is associated with potential morbidity and long term data are not
      available for adolescents undergoing this procedure. As understanding of the
      biologic and psychosocial contributors to eating behaviors and body weight
      regulation increases, multifaceted and targeted behavioral, pharmacological, and
      surgical treatment algorithms should be developed and applied to target the
      underlying pathways involved for the individual child or adolescent with severe
      obesity.

PMID- 27686796
TI  - A computer program to simplify analysis of mass scan data of organometallic
      compounds from high-resolution mass spectrometers.
AB  - RATIONALE: Software accompanying high-resolution mass spectrometers, particularly
      that used for the analysis of organometallic compounds, has lagged the technology
      of the instruments themselves. We have developed a computer program that
      partially fills this gap. METHODS: Given the user's expectation for the number of
      atoms of a target element likely to be in an ion, the program calculates
      isotopologue mass differences for combinations of that element's isotopes and
      their expected intensity ratios relative to the most abundant isotopologue. These
      values are compared with mass differences and intensity ratios found in the
      experimental mass scan data and these metrics feed into a four-factor scoring
      model which ranks the ions as to the likelihood of each containing the specified
      number of the target atoms. The program was tested using experimental data
      obtained for selenomethionine. RESULTS: Across a broad range of sample
      concentrations, the program consistently ranked selenomethionine at or near the
      top of the list of ions that passed the screening and ranking process. Mass scan
      data files in excess of 24,000 records were analyzed in less than one second.
      CONCLUSIONS: The program is quick and efficient at scanning voluminous
      experimental data files for the presence of ions containing the expected number
      of atoms of a target element. Best results were obtained the scarcer the target
      element and the more isotopes it comprised. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 27686797
TI  - A systematic review of measurement properties of the instruments measuring health
      related quality of life in patients with irritable bowel syndrome.
AB  - PURPOSE: The systematic review of patient-reported outcome instruments can allow
      the selection of the most appropriate instrument for use in research and clinical
      practice. There has been no systematic review of the measurement properties of
      irritable bowel syndrome (IBS)-specific health-related quality-of-life (HRQOL)
      instruments. The purposes of this study were to identify all available
      instruments for measuring the IBS-specific HRQOL and to determine which is the
      most appropriate instrument to apply in clinical practice. METHODS: A systematic
      review study was conducted. The MEDLINE, EMBASE, and CINAHL databases were
      searched. The methodological quality of the included studies was assessed using
      the COSMIN (COnsensus-based Standards for the selection of health Measurement
      INstruments) checklist. The measurement property results of each study were
      assessed using Terwee's quality criteria. RESULTS: Seven instruments were
      identified: The Irritable Bowel Syndrome-Quality of Life (IBS-QOL) instrument was
      the only one that had been analyzed in multiple studies, with each of the
      remaining six instruments only being analyzed in a single psychometric study. The
      IBS-QOL demonstrated moderate positive evidence for internal consistency and
      reliability and is the best instrument based on the currently available evidence.
      CONCLUSIONS: Even though the IBS-QOL is currently the best instrument, there is
      conflicting evidence for its underlying structural validity. The factor structure
      or dimensionality of the IBS-QOL needs to be elucidated further.

PMID- 27686798
TI  - Long Non-Coding RNA: An Emerging Paradigm of Pancreatic Cancer.
AB  - Pancreatic cancer remains a worldwide issue and burden that is hard to resolve
      given its low resection rate and chemo-resistance. Early diagnosis and early
      treatment are critical for conquering pancreatic cancer. Therefore, new
      biomarkers for diagnosis and prognosis are urgently needed. Previously,
      researchers mainly focused on protein-coding genetic and epigenetic changes in
      many types of cancers, and regarded the noncoding part as waste. Recently,
      however, long non-coding RNA (lncRNA) has emerged as a major participant in
      carcinogenesis, as it regulates cell proliferation, migration, invasion,
      metastasis, chemo-resistance, etc. The underlying mechanisms are summarized as
      signaling, decoy, guide and scaffold, yet the specific regulation networks remain
      to be uncovered. Several studies have revealed that some lncRNAs are dysregulated
      in pancreatic cancer, participating in biological functions. In this review, we
      will briefly outline the functional lncRNAs in pancreatic cancer, decipher
      possible mechanisms of lncRNAs, and further explore their significance in
      pancreatic cancer.

PMID- 27686800
TI  - Corrigendum.

PMID- 27686799
TI  - Potential clinical and economic outcomes of active beta-D-glucan surveillance
      with preemptive therapy for invasive candidiasis at intensive care units: a
      decision model analysis.
AB  - Early initiation of antifungal treatment for invasive candidiasis is associated
      with change in mortality. Beta-D-glucan (BDG) is a fungal cell wall component and
      a serum diagnostic biomarker of fungal infection. Clinical findings suggested an
      association between reduced invasive candidiasis incidence in intensive care
      units (ICUs) and BDG-guided preemptive antifungal therapy. We evaluated the
      potential cost-effectiveness of active BDG surveillance with preemptive
      antifungal therapy in patients admitted to adult ICUs from the perspective of
      Hong Kong healthcare providers. A Markov model was designed to simulate the
      outcomes of active BDG surveillance with preemptive therapy (surveillance group)
      and no surveillance (standard care group). Candidiasis-associated outcome
      measures included mortality rate, quality-adjusted life year (QALY) loss, and
      direct medical cost. Model inputs were derived from the literature. Sensitivity
      analyses were conducted to evaluate the robustness of model results. In base-case
      analysis, the surveillance group was more costly (1387 USD versus 664 USD) (1 USD
      = 7.8 HKD), with lower candidiasis-associated mortality rate (0.653 versus 1.426
      per 100 ICU admissions) and QALY loss (0.116 versus 0.254) than the standard care
      group. The incremental cost per QALY saved by the surveillance group was 5239
      USD/QALY. One-way sensitivity analyses found base-case results to be robust to
      variations of all model inputs. In probabilistic sensitivity analysis, the
      surveillance group was cost-effective in 50 % and 100 % of 10,000 Monte Carlo
      simulations at willingness-to-pay (WTP) thresholds of 7200 USD/QALY and >=27,800
      USD/QALY, respectively. Active BDG surveillance with preemptive therapy appears
      to be highly cost-effective to reduce the candidiasis-associated mortality rate
      and save QALYs in the ICU setting.

PMID- 27686801
TI  - Differences in alexithymia and emotional awareness in exhaustion syndrome and
      chronic fatigue syndrome.
AB  - Symptoms of Exhaustion Syndrome (ES) and Chronic Fatigue Syndrome (CFS) are
      overlapping and create difficulties of differential diagnosis. Empirical studies
      comparing ES and CFS are scarce. This study aims to investigate if there are any
      emotional differences between ES and CFS. This cross-sectional study compared
      self-reported alexithymia and observer-rated emotional awareness in patients with
      ES (n = 31), CFS (n = 38) and healthy controls (HC) (n = 30). Self-reported
      alexithymia was measured with the Toronto Alexithymia Scale-20 (TAS-20) and
      emotional awareness with an observer-rated performance test, the Level of
      Emotional Awareness Scale (LEAS). Additionally, depression and anxiety were
      scored by the Hospital Anxiety and Depression Scale (HADS). Results show that
      patients with ES expressed higher self-reported alexithymia in the TAS-20
      compared to HC, but had similar emotional awareness capacity in the observer
      rated performance test, the LEAS. Patients with CFS expressed more difficulties
      in identifying emotions compared to HCs, and performed significantly worse in the
      LEAS-total and spent more time completing the LEAS as compared to HC. Correlation
      and multiple regressions analyses revealed that depression and anxiety positively
      correlated with and explained part of the variances in alexithymia scores, while
      age and group explained the major part of the variance in LEAS. Findings of this
      study indicate that emotional status is different in patients with ES and CFS
      with respect to both self-reported alexithymia and observer-rated emotional
      awareness. Emotional parameters should be approached both in clinical
      investigation and psychotherapy for patients with ES and CFS.

PMID- 27686802
TI  - Proteogenomic Tools and Approaches to Explore Protein Coding Landscapes of
      Eukaryotic Genomes.
AB  - Proteogenomic strategies aim to refine genome-wide annotations of protein coding
      features by using actual protein level observations. Most of the currently
      applied proteogenomic approaches include integrative analysis of multiple types
      of high-throughput omics data, e.g., genomics, transcriptomics, proteomics, etc.
      Recent efforts towards creating a human proteome map were primarily targeted to
      experimentally detect at least one protein product for each gene in the genome
      and extensively utilized proteogenomic approaches. The 14 year long wait to get a
      draft human proteome map, after completion of similar efforts to sequence the
      genome, explains the huge complexity and technical hurdles of such efforts.
      Further, the integrative analysis of large-scale multi-omics datasets inherent to
      these studies becomes a major bottleneck to their success. However, recent
      developments of various analysis tools and pipelines dedicated to proteogenomics
      reduce both the time and complexity of such analysis. Here, we summarize notable
      approaches, studies, software developments and their potential applications
      towards eukaryotic genome annotation and clinical proteogenomics.

PMID- 27686803
TI  - Next Generation Sequencing Data and Proteogenomics.
AB  - The field of proteogenomics has been driven by combined advances in next
      generation sequencing (NGS) and proteomic methods. NGS technologies are now both
      rapid and affordable, making it feasible to include sequencing in the clinic and
      academic research setting. Alongside the improvements in sequencing technologies,
      methods in high throughput proteomics have increased the depth of coverage and
      the speed of analysis. The integration of these data types using continuously
      evolving bioinformatics methods allows for improvements in gene and protein
      annotation, and a more comprehensive understanding of biological systems.

PMID- 27686804
TI  - Proteogenomics: Key Driver for Clinical Discovery and Personalized Medicine.
AB  - Proteogenomics is a multi-omics research field that has the aim to efficiently
      integrate genomics, transcriptomics and proteomics. With this approach it is
      possible to identify new patient-specific proteoforms that may have implications
      in disease development, specifically in cancer. Understanding the impact of a
      large number of mutations detected at the genomics level is needed to assess the
      effects at the proteome level. Proteogenomics data integration would help in
      identifying molecular changes that are persistent across multiple molecular
      layers and enable better interpretation of molecular mechanisms of disease, such
      as the causal relationship between single nucleotide polymorphisms (SNPs) and the
      expression of transcripts and translation of proteins compared to mainstream
      proteomics approaches. Identifying patient-specific protein forms and getting a
      better picture of molecular mechanisms of disease opens the avenue for precision
      and personalized medicine. Proteogenomics is, however, a challenging
      interdisciplinary science that requires the understanding of sample preparation,
      data acquisition and processing for genomics, transcriptomics and proteomics.
      This chapter aims to guide the reader through the technology and bioinformatics
      aspects of these multi-omics approaches, illustrated with proteogenomics
      applications having clinical or biological relevance.

PMID- 27686805
TI  - Identification of Small Novel Coding Sequences, a Proteogenomics Endeavor.
AB  - The identification of small proteins and peptides has consistently proven to be
      challenging. However, technological advances as well as multi-omics endeavors
      facilitate the identification of novel small coding sequences, leading to new
      insights. Specifically, the application of next generation sequencing
      technologies (NGS), providing accurate and sample specific transcriptome /
      translatome information, into the proteomics field led to more comprehensive
      results and new discoveries. This book chapter focuses on the inclusion of RNA
      Seq and RIBO-Seq also known as ribosome profiling, an RNA-Seq based technique
      sequencing the +/- 30 bp long fragments captured by translating ribosomes. We
      emphasize the identification of micropeptides and neo-antigens, two distinct
      classes of small translation products, triggering our current understanding of
      biology. RNA-Seq is capable of capturing sample specific genomic variations,
      enabling focused neo-antigen identification. RIBO-Seq can identify translation
      events in small open reading frames which are considered to be non-coding,
      leading to the discovery of micropeptides. The identification of small
      translation products requires the integration of multi-omics data, stressing the
      importance of proteogenomics in this novel research area.

PMID- 27686806
TI  - Using Proteomics Bioinformatics Tools and Resources in Proteogenomic Studies.
AB  - Proteogenomic studies ally the omic fields related to gene expression into a
      combined approach to improve the characterization of biological samples. Part of
      this consists in mining proteomics datasets for non-canonical sequences of amino
      acids. These include intergenic peptides, products of mutations, or of RNA
      editing events hypothesized from genomic, epigenomic, or transcriptomic data.
      This approach poses new challenges for standard peptide identification workflows.
      In this chapter, we present the principles behind the use of peptide
      identification algorithms and highlight the major pitfalls of their application
      to proteogenomic studies.

PMID- 27686807
TI  - Mutant Proteogenomics.
AB  - Identification of mutant proteins in biological samples is one of the emerging
      areas of proteogenomics. Despite the fact that only a limited number of studies
      have been published up to now, it has the potential to recognize novel disease
      biomarkers that have unique structure and desirably high specificity. Such
      properties would identify mutant proteoforms related to diseases as optimal drug
      targets useful for future therapeutic strategies. While mass spectrometry has
      demonstrated its outstanding analytical power in proteomics, the most frequently
      applied bottom-up strategy is not suitable for the detection of mutant proteins
      if only databases with consensus sequences are searched. It is likely that many
      unassigned tandem mass spectra of tryptic peptides originate from single amino
      acid variants (SAAVs). To address this problem, a couple of protein databases
      have been constructed that include canonical and SAAV sequences, allowing for the
      observation of mutant proteoforms in mass spectral data for the first time. Since
      the resulting large search space may compromise the probability of
      identifications, a novel concept was proposed that included identification as
      well as verification strategies. Together with transcriptome based approaches,
      targeted proteomics appears to be a suitable method for the verification of
      initial identifications in databases and can also provide quantitative insights
      to expression profiles, which often reflect disease progression. Important
      applications in the field of mutant proteoform identification have already
      highlighted novel biomarkers in large-scale investigations.

PMID- 27686808
TI  - Proteogenomic Analysis of Single Amino Acid Polymorphisms in Cancer Research.
AB  - The integration of genomics and proteomics has led to the emergence of
      proteogenomics, a field of research successfully applied to the characterization
      of cancer samples. The diagnosis, prognosis and response to therapy of cancer
      patients will largely benefit from the identification of mutations present in
      their genome. The current state of the art of high throughput experiments for
      genome-wide detection of somatic mutations in cancer samples has allowed the
      development of projects such as the TCGA, in which hundreds of cancer genomes
      have been sequenced. This huge amount of data can be used to generate protein
      sequence databases in which each entry corresponds to a mutated peptide
      associated with certain cancer types. In this chapter, we describe a
      bioinformatics workflow for creating these databases and detecting mutated
      peptides in cancer samples from proteomic shotgun experiments. The performance of
      the proposed method has been evaluated using publicly available datasets from
      four cancer cell lines.

PMID- 27686809
TI  - Developments for Personalized Medicine of Lung Cancer Subtypes: Mass Spectrometry
      Based Clinical Proteogenomic Analysis of Oncogenic Mutations.
AB  - Molecular therapies targeting lung cancers with mutated epidermal growth factor
      receptor (EGFR) by EGFR-tyrosin kinase inhibitors (EGFR-TKIs), gefitinib and
      erlotinib, changed the treatment system of lung cancer. It was revealed that drug
      efficacy differs by race (e.g., Caucasians vs. Asians) due to oncogenic driver
      mutations specific to each race, exemplified by gefitinib / erlotinib. The
      molecular target drugs for lung cancer with anaplastic lymphoma kinase (ALK) gene
      translocation (the fusion gene, EML4-ALK) was approved, and those targeting lung
      cancers addicted ROS1, RET, and HER2 have been under development. Both
      identification and quantification of gatekeeper mutations need to be performed
      using lung cancer tissue specimens obtained from patients to improve the
      treatment for lung cancer patients: (1) identification and quantitation data of
      targeted mutated proteins, including investigation of mutation heterogeneity
      within a tissue; (2) exploratory mass spectrometry (MS)-based clinical
      proteogenomic analysis of mutated proteins; and also importantly (3) analysis of
      dynamic protein-protein interaction (PPI) networks of proteins significantly
      related to a subgroup of patients with lung cancer not only with good efficacy
      but also with acquired resistance. MS-based proteogenomics is a promising
      approach to directly capture mutated and fusion proteins expressed in a clinical
      sample. Technological developments are further expected, which will provide a
      powerful solution for the stratification of patients and drug discovery
      (Precision Medicine).

PMID- 27686810
TI  - Proteogenomics for the Study of Gastrointestinal Stromal Tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. Gain-of-function mutations in KIT or platelet-derived
      growth factor receptor alpha (PDGFRA) drive most GISTs, and 85 % of GISTs also
      contain oncogenic mutations in one of two receptor tyrosine kinases. The advent
      of tyrosine kinase inhibitors has had a significant impact on the clinical
      practices for GISTs. However, tumors in more than 80 % of GIST patients acquire
      resistance against treatments with tyrosine kinase inhibitors; thus, driver
      mechanisms of secondary resistance as well as biomarkers for early detection of
      recurrence have been explored for better clinical outcomes. Proteomics is a
      versatile and straightforward approach to finding the molecular basis of
      malignancies as well as the innovative seeds for clinical applications.
      Comprehensive genome, epigenome, and transcriptome data have already been
      obtained and examined together in GISTs, and proteome data has a unique
      additional value in multi-omics studies. Various types of samples were examined
      using proteomics modalities in GIST, suggest the promising utility of proteomic
      approaches.

PMID- 27686811
TI  - Proteogenomics for the Comprehensive Analysis of Human Cellular and Serum
      Antibody Repertoires.
AB  - The vast repertoire of immunoglobulins produced by the immune system is a
      consequence of the huge amount of antigens to which we are exposed every day. The
      diversity of these immunoglobulins is due to different mechanisms (including VDJ
      recombination, somatic hypermutation, and antigen selection). Understanding how
      the immune system is capable of generating this diversity and which are the
      molecular bases of the composition of immunoglobulins are key challenges in the
      immunological field. During the last decades, several techniques have emerged as
      promising strategies to achieve these goals, but it is their combination which
      appears to be the fruitful solution for increasing the knowledge about human
      cellular and serum antibody repertoires.In this chapter, we address the diverse
      strategies focused on the analysis of immunoglobulin repertoires as well as the
      characterization of the genomic and peptide sequences. Moreover, the advantages
      of combining various -omics approaches are discussed through review different
      published studies, showing the benefits in clinical areas.

PMID- 27686812
TI  - Antibody-Based Proteomics.
AB  - Antibody-based proteomic approaches play an important role in high-throughput,
      multiplexed protein expression profiling in health and disease. These antibody
      based technologies will provide (miniaturized) set-ups capable of the
      simultaneously profiling of numerous proteins in a specific, sensitive, and rapid
      manner, targeting high- as well as low-abundant proteins, even in crude proteomes
      such as serum. The generated protein expression patterns, or proteomic snapshots,
      can then be transformed into proteomic maps, or detailed molecular fingerprints,
      revealing the composition of the target (sample) proteome at a molecular level.
      By using bioinformatics, candidate biomarker signatures can be deciphered and
      evaluated for clinical applicability. The approaches will provide unique
      opportunities for e.g. disease diagnostics, biomarker discovery, patient
      stratification, predicting disease recurrence, and evidence-based therapy
      selection. In this review, we describe the current status of the antibody-based
      proteomic approaches, focusing on antibody arrays. Furthermore, the current
      benefits and limitations of the approaches, as well as a set of selected key
      applications outlining the applicative potential will be discussed.

PMID- 27686813
TI  - Patterns of pre-hospital events and management of motorcycle-related injuries in
      a tropical setting.
AB  - This study sought to highlight associated factors and evaluate outcomes of
      motorcycle-related injuries (MCRI) among adults managed in a university teaching
      hospital in south-western Nigeria. The study was a cross-sectional descriptive
      study of 150 adult patients presenting with MCRI at the adult accident and
      emergency unit of the hospital. Information on the use of helmet, alcohol intake,
      number of pillion passengers, type of collision and time of arrival at hospital
      was collected. Patients were followed up and questionnaires were completed after
      discharge, referral or death. The male to female ratio was 4:1 with patients aged
      20-29 years (n = 44, 29.3%) having the highest incidence of MCRI. Only 4 (2.7%)
      patients used helmet at the time of injury. About one-third of the patients (n =
      59, 39.3%) arrived at the hospital within 1-6 hours after injury. The limbs were
      the most frequently involved site of injury, hence orthopaedic procedures
      constituted the highest number of interventions. Mortality rate was 10.7% (16 out
      of 150) with head injury being the leading cause. MCRI requires more emphasis on
      preventive measures. This will play a crucial role in the reduction of the
      associated morbidity and mortality.

PMID- 27686814
TI  - In vitro cytotoxic and genotoxic evaluation of peptides used in nuclear medicine
      (DOTATATE and Ubiquicidin29-41) in CHO-K1 cells.
AB  - Micronucleus (MN) assay constitutes a valuable surrogate to the chromosome
      aberration technique for in vitro testing of the genotoxicity of substances. As
      test substances, two peptidic compounds (DOTATATE and Ubiquicidin29-41) used in
      nuclear medicine, were tested for in vitro cytotoxicity and genotoxicity in CHO
      K1 cells. None of the compounds showed detectable cytotoxicity (0.5-7.3 ng/mL for
      DOTATATE and 0.3-4.5 ng/mL for UBI29-41), genotoxicity (0.72, 7.2 and 72.0 ng/ml
      for DOTATATE and 0.45, 4.5 and 45.0 ng/mL for UBI29-41) or cell cycle changes as
      compared to untreated controls at the concentrations tested. Statistical analysis
      showed good concordance between two independent analysts. The results corroborate
      the notion of the safety of the compounds and present improvements of the in
      vitro MN assay when performed in a pre-clinical trial context that increase the
      throughput of small-to-medium testing facilities as an alternative to high
      content screening systems.

PMID- 27686818
TI  - Shrinking the food-print: A qualitative study into consumer perceptions,
      experiences and attitudes towards healthy and environmentally friendly food
      behaviours.
AB  - Internationally, there is increasing recognition of the importance of multilevel
      policies and actions that address healthy and environmentally friendly food
      behaviours. However it is not yet clear which actions are most suitable to
      support consumers to adopt both behaviours concurrently. To this end, we
      undertook a qualitative study to assess consumer perceptions, experiences and
      attitudes towards healthy and environmentally friendly foods and four target
      behaviours: reducing overconsumption of food beyond energy needs, reducing
      consumption of low-nutrient energy dense foods, eating less animal- and more
      plant-derived foods, and reducing food waste. Online in-depth interviews were
      held with 29 Australian food shoppers representing different levels of
      involvement with health and environment in daily food choices. The results
      indicate that compared to health, the relationship between food and the
      environment is rarely considered by consumers. The four target food behaviours
      were primarily associated and motivated by an impact on health, except for not
      wasting foods. Participants had the most positive attitude and highest motivation
      for eating less processed and packaged foods, mostly to avoid excessive packaging
      and 'chemicals' in foods. This was followed by the behaviours reducing food waste
      and overconsumption. Conversely, there was a predominantly negative attitude
      towards, and low motivation for, eating less animal-derived products and more
      plant based foods. Overall, consumers found a joined concept of healthy and
      environmentally friendly foods an acceptable idea. We recommend that health
      should remain the overarching principle for policies and actions concerned with
      shifting consumer behaviours, as this personal benefit appears to have a greater
      potential to support behaviour change. Future consumer focused work could pay
      attention to framing behavioural messages, providing intermediate behavioural
      goals, and a multiple target approach to change habitual behaviours.

PMID- 27686819
TI  - Yogurt's flexible image during its rise in popularity in post-war Belgium.
AB  - The consumption of yogurt in Western countries has risen for over a century,
      first slowly, then more rapidly. The purpose of the present study was to
      investigate this prolonged phase of growth, by examining the popularity and the
      projected image of yogurt. A particular focus was on the way these aspects were
      reflected in consumption patterns and media representations. The data showed how
      during its period of rapid popularization, yogurt's visibility in the media
      greatly increased. It was concluded that the product's image was highly flexible
      in post-war decades, evidenced by the multi-pronged approach taken by marketers.
      Yogurt was not only advertised as both tasty and healthy, but also as natural and
      convenient, a strategy that appears to have been informed by consumers'
      preferences and existing cultural values. This demonstrates how a high degree of
      product differentiation and diversification during a product's growth stage can
      result in a heterogeneous image, allowing for a broad range of marketing
      strategies.

PMID- 27686821
TI  - Release of synthetic microplastic plastic fibres from domestic washing machines:
      Effects of fabric type and washing conditions.
AB  - Washing clothes made from synthetic materials has been identified as a
      potentially important source of microscopic fibres to the environment. This study
      examined the release of fibres from polyester, polyester-cotton blend and acrylic
      fabrics. These fabrics were laundered under various conditions of temperature,
      detergent and conditioner. Fibres from waste effluent were examined and the mass,
      abundance and fibre size compared between treatments. Average fibre size ranged
      between 11.9 and 17.7MUm in diameter, and 5.0 and 7.8mm in length. Polyester
      cotton fabric consistently shed significantly fewer fibres than either polyester
      or acrylic. However, fibre release varied according to wash treatment with
      various complex interactions. We estimate over 700,000 fibres could be released
      from an average 6kg wash load of acrylic fabric. As fibres have been reported in
      effluent from sewage treatment plants, our data indicates fibres released by
      washing of clothing could be an important source of microplastics to aquatic
      habitats.

PMID- 27686820
TI  - Metabolic, endocrine and appetite-related responses to acute and daily milk snack
      consumption in healthy, adolescent males.
AB  - Comprising of two experiments, this study assessed the metabolic, endocrine and
      appetite-related responses to acute and chronic milk consumption in adolescent
      males (15-18 y). Eleven adolescents [mean +/- SD age: 16.5 +/- 0.9 y; BMI: 23.3
      +/- 3.3 kg/m2] participated in the acute experiment and completed two laboratory
      visits (milk vs. fruit-juice) in a randomized crossover design, separated by 7-d.
      Seventeen adolescents [age: 16.1 +/- 0.9 y; BMI: 21.8 +/- 3.7 kg/m2] completed
      the chronic experiment. For the chronic experiment, a parallel design with two
      groups was used. Participants were randomly allocated and consumed milk (n = 9)
      or fruit-juice (n = 8) for 28-d, completing laboratory visits on the first
      (baseline, day-0) and last day (follow-up, day-28) of the intervention phase. On
      laboratory visits (for both experiments), measures of appetite, metabolism and
      endocrine responses were assessed at regular intervals. In addition, eating
      behavior was quantified by ad libitum assessment under laboratory conditions and
      in the free-living environment by weighed food record. Acute milk intake
      stimulated glucagon (P = 0.027 [16.8 pg mL; 95% CI: 2.4, 31.3]) and reduced ad
      libitum energy intake relative to fruit-juice (P = 0.048 [-651.3 kJ; 95% CI: 
      1294.1, -8.6]), but was comparable in the free-living environment. Chronic milk
      intake reduced free-living energy intake at the follow-up visit compared to
      baseline (P = 0.013 [-1910.9 kJ; 95% CI: -554.6, -3267.2]), whereas the opposite
      was apparent for fruit-juice. Relative to baseline, chronic milk intake increased
      the insulin response to both breakfast (P = 0.031) and mid-morning milk
      consumption (P = 0.050) whilst attenuating blood glucose (P = 0.025). Together,
      these findings suggest milk consumption impacts favorably on eating behavior in
      adolescent males, potentially through integrated endocrine responses.

PMID- 27686822
TI  - Microplastics in the Southern Ocean.
AB  - A field survey to collect microplastics with sizes <5mm was conducted in the
      Southern Ocean in 2016. We performed five net-tows and collected 44 pieces of
      plastic. Total particle counts of the entire water column, which is free of
      vertical mixing, were computed using the surface concentration (particle count
      per unit seawater volume) of microplastics, wind speed, and significant wave
      height during the observation period. Total particle counts at two stations near
      Antarctica were estimated to be in the order of 100,000pieceskm-2.

PMID- 27686823
TI  - Marine copepod cytochrome P450 genes and their applications for molecular
      ecotoxicological studies in response to oil pollution.
AB  - Recently, accidental spills of heavy oil have caused adverse effects in marine
      organisms. Oil pollution can induce damages on development and reproduction,
      linking with detrimental effects on diverse molecular levels of genes and
      proteins in plankton and fish. However, most information was mainly focused on
      marine vertebrates and consequently, limited information was available in marine
      invertebrates. Furthermore, there is still a lack of knowledge bridging in vivo
      endpoints with the functional regulation of cytochrome P450 (CYP) genes in
      response to oil spill pollution in marine invertebrates. In this paper, adverse
      effects of oil spill pollution in marine invertebrates are summarized with the
      importance of CYP genes as a potential biomarker, applying for environmental
      monitoring to detect oil spill using marine copepods.

PMID- 27686825
TI  - Bacterial protein toxins P. Falmagne, J.E. Alouf, F.J. Fehrenbach, J.
      Jeljaszewicz, M. Thelestam (Eds.) : Zentralblatt fur Bakteriologie und Hygiene,
      Supplement Vol. 15 Gustav Fischer Verlag, Stuttgart-New York 1986 398 pages, 93
      figures, 64 tables.

PMID- 27686826
TI  - A Modified Delphi Study to Identify Factors Associated With Clinical
      Deterioration in Hospitalized Children.
AB  - OBJECTIVE: Hospitalized children who are admitted to the inpatient ward can
      deteriorate and require unplanned transfer to the PICU. Studies designed to
      validate early warning scoring systems have focused mainly on abnormalities in
      vital signs in patients admitted to the inpatient ward. The objective of this
      study was to determine the patient and system factors that experienced clinicians
      think are associated with progression to critical illness in hospitalized
      children. METHODS: We conducted a modified Delphi study with 3 iterations,
      administered electronically. The expert panel consisted of 11 physician and
      nonphysician health care providers from hospitals in Canada and the United
      States. RESULTS: Consensus was reached that 21 of the 57 factors presented are
      associated with clinical deterioration in hospitalized children. The final list
      of variables includes patient characteristics, signs and symptoms in the
      emergency department, emergency department management, and system factors.
      CONCLUSIONS: We generated a list of variables that can be used in future
      prospective studies to determine if they are predictors of clinical deterioration
      on the inpatient ward.

PMID- 27686828
TI  - Historical Milestones in Oral and Maxillofacial Surgery.

PMID- 27686824
TI  - Metastasis: an early event in cancer progression.
AB  - PURPOSE: Metastasis is the leading cause of death for a majority of cancer
      patients, and thus the need to understand the biology of metastasis becomes
      increasingly acute. When metastasis is initiated in tumor progression remains
      obscure. Better understanding of mechanisms regulating acquisition of metastatic
      ability in tumor cells will provide novel therapeutic targets and prevention of
      metastasis in clinics accompanied with the treatment of the primary tumor might
      be helpful in reducing metastasis-related mortality. METHODS: A literature search
      was performed in multiple electronic databases. Research papers from clinical
      reports to experimental studies on metastasis were analyzed. RESULTS: The article
      discusses tumor heterogeneity and genomic instability in the context of
      metastasis and tumor cell dissemination. And then we review biological mechanism
      of metastasis at an early stage in both intracellular (CSCs and CTCs) and
      extracellular (microenvironment) context. Finally, current development of anti
      metastatic therapies is summarized. CONCLUSIONS: Metastasis could be initiated at
      an early point of tumor progression. Therefore, early intervention on metastasis
      should be applied among cancer patients in clinical settings.

PMID- 27686829
TI  - [Schools, essential places during vaccination campaigns against meningitis].

PMID- 27686830
TI  - Editorial.

PMID- 27686832
TI  - Cardiotoxicity of nano-particles.
AB  - Nano-particles (NPs) are used in industrial and biomedical fields such as
      cosmetics, food additives and biosensors. Beside their favorable properties,
      nanoparticles are responsible for toxic effects. Local adverse effects and/or
      systemic toxicity are described with nanoparticle delivery to target organs of
      the human body. Animal studies provide evidence for the aforementioned toxicity.
      Cardiac function is a specific target of nanoparticles. Thus, reviewing the
      current bibliography on cardiotoxicity of nanoparticles and specifically of
      titanium, zinc, silver, carbon, silica and iron oxide nano-materials is the aim
      of this study.

PMID- 27686831
TI  - Glabridin-induced vasorelaxation: Evidence for a role of BKCa channels and cyclic
      GMP.
AB  - BACKGROUND AND PURPOSE: Glabridin is a major flavonoid in Glycyrrhiza glabra
      (licorice) root, a traditional Asian medicine. Glabridin is reported to have anti
      atherogenic, anti-inflammatory and anti-nephritic properties; however its effects
      on vascular tone remain unexplored. EXPERIMENTAL APPROACH: We examined the effect
      of glabridin on rat main mesenteric artery using isometric myography and also
      ELISA to measure cGMP levels. KEY RESULTS: Glabridin (30MUM) relaxed arteries pre
      constricted with the thromboxane A2 analog U46619 (0.2MUM) by ~60% in an
      endothelium-independent manner. Relaxation to 30MUM glabridin was abolished by
      the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one
      (1MUM) and by the BKCa channel blocker tetraethyammonium (1mM) but was unaffected
      by the estrogen receptor antagonist ICI182780. The concentration-response curve
      to glabridin (0.1 to 30MUM) was downshifted by the KATP channel blocker
      glibenclamide (10MUM), the KV channel blocker 4-aminopyridine (300MUM), and the
      KIR blocker BaCl2 (30MUM). In U46619-contracted arteries partially relaxed by
      0.1MUM sodium nitroprusside, application of 10 and 30nM glabridin caused
      additional vasorelaxation. Glabridin (30MUM) approximately doubled tissue [cyclic
      GMP]. Application of the phosphodiesterase inhibitor isobutylmethylxanthine
      caused a much larger rise in [cyclic GMP], and glabridin failed to cause
      vasorelaxation or a further rise in [cGMP] when co-applied with IBMX. CONCLUSIONS
      AND IMPLICATIONS: Vasorelaxation to glabridin is dependent on the opening of K+
      channels, particularly BKCa, probably caused by a rise in cellular [cyclic GMP]
      owing to phosphodiesterase inhibition. In the presence of sodium nitroprusside an
      effect of glabridin is observed at nM concentrations, similar those measured in
      plasma following human ingestion of licorice flavonoid oil.

PMID- 27686833
TI  - Long-term follow-up of Japanese encephalitis chimeric virus vaccine: Immune
      responses in children.
AB  - BACKGROUND: A single dose of live attenuated Japanese encephalitis chimeric virus
      vaccine (JE-CV) was shown to be immunogenic and well tolerated when given either
      as a booster to formalin-inactivated Japanese encephalitis (JE)-vaccine (mouse
      brain-derived vaccine [MBDV])-primed 2-5-year-olds, or as a primary vaccination
      to JE-vaccine-naive 12-24-month-old toddlers in Thailand. A 5-year follow-up
      assessment of immune response persistence over time was conducted. METHODS: Four
      additional visits (at 2, 3, 4, and 5years) for immunologic assessments were added
      to the original 12-month open-label crossover study, in which 100 healthy
      children aged 2-5years with a history of two-dose primary vaccination with MBDV
      (according to the Thai Expanded Program for Immunization schedule), and 200
      healthy JE-vaccine-naive 12-24-month-old toddlers, were randomized 1:1 to receive
      JE-CV, containing ?4 log10 plaque forming units, 1month before or after hepatitis
      A control vaccine. RESULTS: In MBDV-primed 2-5-year-olds (n=78), the immune
      response to the JE-CV vaccine persisted up to at least 5years after vaccination
      with a single dose of JE-CV, with all (n=78) children seroprotected at the year 5
      visit (geometric mean titers [GMT]: 2521/dil). There was no decrease of
      seroprotection rate over time (100% at 6months post-vaccination and 96.8% (90.3
      98.9) at 5yearspost-vaccination). In JE-vaccine-naive toddlers, a protective
      immune response persisted up to at least 5years in 58.8% (50.9-66.4) after a
      single-dose administration of JE-CV (GMT 26.71/dil; sensitivity analysis).
      CONCLUSIONS: A single-dose of JE-CV as a booster following MBDV administration
      provided long-lasting immunity. In JE-vaccine-naive toddlers, despite relatively
      high seroprotection rates persisting over time, a subsequent booster dose is
      recommended following a JE-CV primary vaccination for long-term protection. This
      study was registered on www.clinicaltrials.gov (NCT00621764).

PMID- 27686834
TI  - Integrating pharmacies into public health program planning for pandemic influenza
      vaccine response.
AB  - BACKGROUND: During an influenza pandemic, to achieve early and rapid vaccination
      coverage and maximize the benefit of an immunization campaign, partnerships
      between public health agencies and vaccine providers are essential. Immunizing
      pharmacists represent an important group for expanding access to pandemic
      vaccination. However, little is known about nationwide coordination between
      public health programs and pharmacies for pandemic vaccine response planning.
      METHODS: To assess relationships and planning activities between public health
      programs and pharmacies, we analyzed data from Centers for Disease Control and
      Prevention assessments of jurisdictions that received immunization and emergency
      preparedness funding from 2012 to 2015. RESULTS: Forty-seven (88.7%) of 53
      jurisdictions reported including pharmacies in pandemic vaccine distribution
      plans, 24 (45.3%) had processes to recruit pharmacists to vaccinate, and 16
      (30.8%) of 52 established formal relationships with pharmacies. Most
      jurisdictions plan to allocate less than 10% of pandemic vaccine supply to
      pharmacies. DISCUSSION: While most jurisdictions plan to include pharmacies as
      pandemic vaccine providers, work is needed to establish formalized agreements
      between public health departments and pharmacies to improve pandemic preparedness
      coordination and ensure that vaccinating pharmacists are fully utilized during a
      pandemic.

PMID- 27686835
TI  - Equity in disease prevention: Vaccines for the older adults - a national
      workshop, Australia 2014.
AB  - On the 20th June, 2014 the National Health and Medical Research Council's Centre
      for Research Excellence in Population Health "Immunisation in under Studied and
      Special Risk Populations", in collaboration with the Public Health Association of
      Australia, hosted a workshop "Equity in disease prevention: vaccines for the
      older adults". The workshop featured international and national speakers on
      ageing and vaccinology. The workshop was attended by health service providers,
      stakeholders in immunisation, ageing, primary care, researchers, government and
      non-government organisations, community representatives, and advocacy groups. The
      aims of the workshop were to: provide an update on the latest evidence around
      immunisation for the older adults; address barriers for prevention of infection
      in the older adults; and identify immunisation needs of these groups and provide
      recommendations to inform policy. There is a gap in immunisation coverage of
      funded vaccines between adults and infants. The workshop reviewed provider
      misconceptions, lack of Randomised Control Trials (RCT) and cost-effectiveness
      data in the frail elderly, loss of autonomy, value judgements and ageism in
      health care and the need for an adult vaccination register. Workshop
      recommendations included recognising the right of elderly people to prevention,
      the need for promotion in the community and amongst healthcare workers of the
      high burden of vaccine preventable diseases and the need to achieve high levels
      of vaccination coverage, in older adults and in health workers involved in their
      care. Research into new vaccine strategies for older adults which address poor
      coverage, provider attitudes and immunosenescence is a priority. A well designed
      national register for tracking vaccinations in older adults is a vital and basic
      requirement for a successful adult immunisation program. Eliminating financial
      barriers, by addressing inequities in the mechanisms for funding and subsidising
      vaccines for the older adults compared to those for children, is important to
      improve equity of access and vaccination coverage. Vaccination coverage rates
      should be included in quality indicators of care in residential aged care for
      older adults. Vaccination is key to healthy ageing, and there is a need to focus
      on reducing the immunisation gap between adults and children.

PMID- 27686837
TI  - The risk of hepatocellular carcinoma after sustained virological response in
      patients treated with the new direct-acting antiviral drugs: should we be worry
      about it?

PMID- 27686836
TI  - The innate immune response to RSV: Advances in our understanding of critical
      viral and host factors.
AB  - Respiratory syncytial virus (RSV) causes mild to severe respiratory illness in
      humans and is a major cause of hospitalizations of infants and the elderly. Both
      the innate and the adaptive immune responses contribute to the control of RSV
      infection, but despite successful viral clearance, protective immunity against
      RSV re-infection is usually suboptimal and infections recur. Poor understanding
      of the mechanisms limiting the induction of long-lasting immunity has delayed the
      development of an effective vaccine. The innate immune response plays a critical
      role in driving the development of adaptive immunity and is thus a crucial
      determinant of the infection outcome. Advances in recent years have improved our
      understanding of cellular and viral factors that influence the onset and quality
      of the innate immune response to RSV. These advances include the identification
      of a complex system of cellular sensors that mediate RSV detection and stimulate
      transcriptome changes that lead to virus control and the discovery that cell
      stress and apoptosis participate in the control of RSV infection. In addition, it
      was recently demonstrated that defective viral genomes (DVGs) generated during
      RSV replication are the primary inducers of the innate immune response. Newly
      discovered host pathways involved in the innate response to RSV, together with
      the potential generation of DVG-derived oligonucleotides, present various novel
      opportunities for the design of vaccine adjuvants able to induce a protective
      response against RSV and similar viruses.

PMID- 27686839
TI  - Betterment, undermining, support and distortion: A heuristic model for the
      analysis of pressure on evaluators.
AB  - Evaluations can only serve as a neutral evidence base for policy decision-making
      as long as they have not been altered along non-scientific criteria. Studies show
      that evaluators are repeatedly put under pressure to deliver results in line with
      given expectations. The study of pressure and influence to misrepresent findings
      is hence an important research strand for the development of evaluation praxis. A
      conceptual challenge in the area of evaluation ethics research is the fact that
      pressure can be not only negative, but also positive. We develop a heuristic
      model of influence on evaluations that does justice to this ambivalence of
      influence: the BUSD-model (betterment, undermining, support, distortion). The
      model is based on the distinction of two dimensions, namely 'explicitness of
      pressure' and 'direction of influence'. We demonstrate how the model can be
      applied to understand pressure and offer a practical tool to distinguish positive
      from negative influence in the form of three so-called differentiators
      (awareness, accordance, intention). The differentiators comprise a practical
      component by assisting evaluators who are confronted with influence.

PMID- 27686838
TI  - CCL18 synergises with high concentrations of glucose in stimulating fibronectin
      production in human renal tubuloepithelial cells.
AB  - BACKGROUND: Diabetic nephropathy is the leading cause of end stage kidney disease
      worldwide. The pathogenesis of this disease remains elusive and multiple factors
      have been implicated. These include the effects of hyperglycaemia, haemodynamic
      and metabolic factors, and an inflammatory process that stimulates cellular
      signalling pathways leading to disease progression and severe fibrosis.
      Fibronectin (Fn) is an important protein of the extracellular matrix that is
      essential in fibrosis and its presence in increased amounts has been identified
      in the kidney in diabetic nephropathy. METHODS: Proximal tubuloepithelial (HK-2)
      cells were stimulated with high glucose (30 mM D-glucose) or glycated albumin
      (500 MUg/mmol) + 4 mM D-glucose or their controls, Mannitol (26 mM + 4 mM D
      glucose) and 4 mM D-glucose, respectively. Following 48 h of stimulation the
      supernatant was collected and MTT [3-(4,5-dimethylthiazole-2,5
      diphenyltetrazolium bromide] assay performed to assess cell viability. HK-2 cells
      were also stimulated in the above environments with recombinant CCL18 (rCCL18) or
      MCP-1 (rMCP-1) for 48 h with quantification of Fn levels using ELISA. RESULTS: Co
      stimulation of HK-2 cells with high concentrations of glucose and rCCL18
      significantly increased Fn (p < 0.001), in comparison to high concentrations of
      glucose alone. HK-2 cells stimulated with glycated albumin consistently produced
      Fn and this did not alter following co-stimulation with rCCL18 or rMCP-1.
      CONCLUSION: This study demonstrates how stimulation with a specific chemokine
      CCL18 in high glucose upregulates the production of Fn from proximal
      tubuloepithelial cells. This may be relevant to the development of renal fibrosis
      in diabetic nephropathy.

PMID- 27686840
TI  - Amniopatch treatment of iatrogenic preterm premature rupture of membranes
      (iPPROM) after fetoscopic laser surgery for twin-twin transfusion syndrome.
AB  - OBJECTIVES: Amniopatch is a proposed treatment of iatrogenic preterm premature
      rupture of membranes (iPPROM). We studied characteristics associated with
      successful amniopatch treatment of iPPROM after fetoscopic laser surgery for twin
      twin transfusion syndrome. METHODS: Patients with iPPROM within 15 days of laser
      surgery treated with an amniopatch were studied. Factors associated with
      amniopatch success (i.e. cessation of leakage with normalization of amniotic
      fluid volume) were tested univariately and in multivariate logistic regression
      models. Continuous variables are expressed as median (range). RESULTS: Of 1124
      patients undergoing laser surgery, 19 (1.7%) had iPPROM and subsequent
      amniopatch. Twelve (63.2%) were successful. Latency in days from iPPROM to
      delivery was greater in the successful group (114.0 [87.0-141.0]) versus (44.0
      [3.9-88.0], p = 0.0005), which translated into greater gestational age (GA)
      (weeks) at delivery (35.1 [30.9-39.4] versus 28.1 [22.0-31.0], p = 0.0005). The
      30-day survival of the affected recipient twin was improved (100% versus 57.1%, p
      = 0.0361). After multivariate testing, GA < 20 weeks at the time of the
      amniopatch placement was the only variable that remained associated with
      successful sealing of the membranes. CONCLUSIONS: Treatment of iPPROM via
      amniopatch was successful in almost two-thirds of cases and was associated with
      higher GA at delivery and improved perinatal survival.

PMID- 27686841
TI  - Women's views about the timing of birth.
AB  - BACKGROUND: Estimated date of birth (EDB) is used to guide the care provided to
      women during pregnancy and birth, although its imprecision is recognised.
      Alternatives to the EDB have been suggested for use with women however their
      attitudes to timing of birth information have not been examined. AIMS: To explore
      women's expectations of giving birth on or near their EDB, and their attitudes to
      alternative estimates for timing of birth. METHODS: A survey of pregnant women
      attending four public hospitals in Sydney, Australia, between July and December
      2012. RESULTS: Among 769 surveyed women, 42% expected to birth before their due
      date, 16% after the due date, 15% within a day or so of the due date, and 27% had
      no expectations. Nulliparous women were more likely to expect to give birth
      before their due date. Women in the earlier stages of pregnancy were more likely
      to have no expectations or to expect to birth before the EDB while women in later
      pregnancy were more likely to expect birth after their due date. For timing of
      birth information, only 30% of women preferred an EDB; the remainder favoured
      other options. CONCLUSIONS: Most women understood the EDB is imprecise. The
      majority of women expressed a preference for timing of birth information in a
      format other than an EDB. In support of woman-centred care, clinicians should
      consider discussing other options for estimated timing of birth information with
      the women in their care.

PMID- 27686842
TI  - Can antenatal classes reduce the rate of cesarean section in southern Italy?
AB  - BACKGROUND: Among European Countries, Italy has the highest rate of cesarean
      section (36.8%), and in the Campania region this rate reaches 60.0%. QUESTION: We
      conducted a retrospective cohort study to evaluate whether participation in
      antenatal classes during pregnancy reduces the rate of cesarean delivery in
      southern Italy. METHODS: We selected three local health authorities, with the
      lowest, the highest, and an intermediate rate of cesarean delivery. The study
      included 1893 mothers who brought their children for vaccination and were
      interviewed about their participation in antenatal classes and their obstetric
      history. FINDINGS: The main causes of cesarean section given in the interview
      were clinical indications (61.0%), previous cesarean section (31.0%) and woman's
      request (8.0%). When we excluded emergency cesarean delivery, we found a moderate
      association between participation in antenatal classes and cesarean section
      reduction (relative risk=1.27; 95% CI=1.08-1.49; in percentage values from 49.3%
      to 38.8%). Private hospitals and the two local health authorities with higher
      baseline rates of cesarean section showed an enhanced reduction of these rates.
      CONCLUSION: Our paper shows moderate efficacy of antenatal classes, which reduced
      the occurrence of cesarean section by about 10%. However, the cesarean section
      rate remained high. As it is possible that different classes have a different
      level of efficacy, a further study on a standardized model of an antenatal
      classes is in progress, to assess its efficacy in term of cesarean section
      reduction, with the purpose of its widespread implementation to the whole region.

PMID- 27686843
TI  - Does neuroinflammation drive the relationship between tau hyperphosphorylation
      and dementia development following traumatic brain injury?
AB  - A history of traumatic brain injury (TBI) is linked to an increased risk for the
      later development of dementia. This encompasses a variety of neurodegenerative
      diseases including Alzheimer's Disease (AD) and chronic traumatic encephalopathy
      (CTE), with AD linked to history of moderate-severe TBI and CTE to a history of
      repeated concussion. Of note, both AD and CTE are characterized by the abnormal
      accumulation of hyperphosphorylated tau aggregates, which are thought to play an
      important role in the development of neurodegeneration. Hyperphosphorylation of
      tau leads to destabilization of microtubules, interrupting axonal transport,
      whilst tau aggregates are associated with synaptic dysfunction. The exact
      mechanisms via which TBI may promote the later tauopathy and its role in the
      later development of dementia are yet to be fully determined. Following TBI, it
      is proposed that axonal injury may provide the initial perturbation of tau, by
      promoting its dissociation from microtubules, facilitating its phosphorylation
      and aggregation. Altered tau dynamics may then be exacerbated by the chronic
      persistent inflammatory response that has been shown to persist for decades
      following the initial impact. Importantly, immune activation has been shown to
      play a role in accelerating disease progression in other tauopathies, with pro
      inflammatory cytokines, like IL-1beta, shown to activate kinases that promote tau
      hyperphosphorylation. Thus, targeting the inflammatory response in the sub-acute
      phase following TBI may represent a promising target to halt the alterations in
      tau dynamics that may precede overt neurodegeneration and later development of
      dementia.

PMID- 27686845
TI  - Cardiovascular and all-cause mortality in patients with type 2 diabetes mellitus
      and chronic kidney disease.

PMID- 27686844
TI  - A survey of neuroimmune changes in pregnant and postpartum female rats.
AB  - During pregnancy and the postpartum period, the adult female brain is remarkably
      plastic exhibiting modifications of neurons, astrocytes and oligodendrocytes.
      However, little is known about how microglia, the brain's innate immune cells,
      are altered during this time. In the current studies, microglial density, number
      and morphological phenotype were analyzed within multiple regions of the maternal
      brain that are known to show neural plasticity during the peripartum period
      and/or regulate peripartum behavioral changes. Our results show a significant
      reduction in microglial density during late pregnancy and the early-mid
      postpartum period in the basolateral amygdala, medial prefrontal cortex, nucleus
      accumbens shell and dorsal hippocampus. In addition, microglia numbers were
      reduced postpartum in all four brain regions, and these reductions occurred
      primarily in microglia with a thin, ramified morphology. Across the various
      measures, microglia in the motor cortex were unaffected by reproductive status.
      The peripartum decrease in microglia may be a consequence of reduced
      proliferation as there were fewer numbers of proliferating microglia, and no
      changes in apoptotic microglia, in the postpartum hippocampus. Finally,
      hippocampal concentrations of the cytokines interleukin (IL)-6 and IL-10 were
      increased postpartum. Together, these data point to a shift in the maternal
      neuroimmune environment during the peripartum period that could contribute to
      neural and behavioral plasticity occurring during the transition to motherhood.

PMID- 27686847
TI  - Selected reaction monitoring mass spectrometry for relative quantification of
      proteins involved in cellular life and death processes.
AB  - Monitoring of proteins involved in cellular life and death processes is of high
      scientific interest since it permits the elucidation of functional changes in a
      variety of diseases. In this study, we have developed a nanoLC-MS/MS assay for
      the simultaneous detection and quantification of 24 selected proteins that are
      known to be important for cellular homeostasis. The Selected Reaction Monitoring
      (SRM) assay applies heavy-labeled peptide analogues for the relative
      quantification of proteins with central functions in cellular stress and
      metabolism, including many mitochondrial proteins. The assay includes proteins
      involved in the quality control of mitochondrial proteins, oxidative stress,
      respiratory chain, and fatty acid degradation, as well as the cytosolic
      glyceraldehyde 3-phosphate dehydrogenase, lactate dehydrogenase and ribosomal
      proteins. The assay can thus quantitate the balance between mitochondrial and
      cytosolic pathways, which is relevant in many disease states, and can be studied
      by comparing patient and control samples. The measured validation parameters
      showed satisfactory results for the proteins included in the analysis. The linear
      range of the monitored proteins was 0.01-20nM, with a median precision of less
      than 10%. The assay performed well in monitoring proteins in both cultured human
      skin fibroblast cells as well as in isolated peripheral blood mononuclear cells.
      We therefore believe that this assay is applicable for the study of cellular
      stress response in various types of cell defects and disease states.

PMID- 27686849
TI  - Redox signaling and oxidative stress: Cross talk with TNF-related apoptosis
      inducing ligand activity.
AB  - Redox regulation plays a key role in several physiopathological contexts and free
      radicals, from nitric oxide and superoxide anion up to other forms of reactive
      oxygen species (ROS), have been demonstrated to be involved in different
      biological and regulatory processes. The data reported in the current literature
      describe a link between ROS, inflammation and programmed cell death that is
      attracting interest as new pathways to be explored and targeted for therapeutic
      purposes. In this light, there is also growing attention to the involvement of
      this link in the activity of the TNF-related apoptosis inducing ligand (TRAIL).
      TRAIL is a member of the TNF ligands super family able to mediate multiple
      intracellular signals, with the potential to lead to a range of biological
      effects in different cell types. In particular, the hallmark of TRAIL is the
      ability to induce selective apoptosis in transformed cells leaving normal cells
      almost unaffected and this feature has already opened the door to several
      clinical studies for cancer treatment. Moreover, TRAIL plays a role in several
      physiological and pathological processes of both innate and adaptive immune
      systems and of the cardiovascular context, with a strong clinical potential.
      Nonetheless, several issues still need to be clarified about the signaling
      mediated by TRAIL to gain deeper insight into its therapeutic potential. In this
      light, the aim of this review is to summarize the main preclinical evidences
      about the interplay between TRAIL and redox signaling, with particular emphasis
      to the implications in vascular physiopathology and cancer.

PMID- 27686850
TI  - Proteolytic degradation pathways in health and disease.

PMID- 27686848
TI  - Trends and advances in tumor immunology and lung cancer immunotherapy.
AB  - Among several types of tumor, lung cancer is considered one of the most fatal and
      still the main cause of cancer-related deaths. Although chemotherapeutic agents
      can improve survival and quality of life compared with symptomatic treatment,
      cancers usually still progress after chemotherapy and are often aggravated by
      serious side effects. In the last few years there has been a growing interest in
      immunotherapy for lung cancer based on promising preliminary results in achieving
      meaningful and durable treatments responses with minimal manageable toxicity.
      This article is divided into two parts, the first part discusses the role of
      human immune system in controlling and eradicating cancer and the mechanisms of
      immune response evasion by tumor. The second part reviews the recent progress
      made in immunotherapy for lung cancer with results from trials evaluating
      therapeutic vaccines in addition to immune checkpoint blockade, specifically
      cytotoxic T lymphocyte associated protein 4, programmed death receptor 1 pathway,
      using monoclonal antibodies.

PMID- 27686851
TI  - Executable medical guidelines with Arden Syntax-Applications in dermatology and
      obstetrics.
AB  - INTRODUCTION: Clinical decision support systems (CDSSs) are being developed to
      assist physicians in processing extensive data and new knowledge based on recent
      scientific advances. Structured medical knowledge in the form of clinical alerts
      or reminder rules, decision trees or tables, clinical protocols or practice
      guidelines, score algorithms, and others, constitute the core of CDSSs. Several
      medical knowledge representation and guideline languages have been developed for
      the formal computerized definition of such knowledge. One of these languages is
      Arden Syntax for Medical Logic Systems, an International Health Level Seven (HL7)
      standard whose development started in 1989. Its latest version is 2.10, which was
      presented in 2014. In the present report we discuss Arden Syntax as a modern
      medical knowledge representation and processing language, and show that this
      language is not only well suited to define clinical alerts, reminders, and
      recommendations, but can also be used to implement and process computerized
      medical practice guidelines. METHODS: This section describes how contemporary
      software such as Java, server software, web-services, XML, is used to implement
      CDSSs based on Arden Syntax. Special emphasis is given to clinical decision
      support (CDS) that employs practice guidelines as its clinical knowledge base.
      RESULTS: Two guideline-based applications using Arden Syntax for medical
      knowledge representation and processing were developed. The first is a software
      platform for implementing practice guidelines from dermatology. This application
      employs fuzzy set theory and logic to represent linguistic and propositional
      uncertainty in medical data, knowledge, and conclusions. The second application
      implements a reminder system based on clinically published standard operating
      procedures in obstetrics to prevent deviations from state-of-the-art care. A to
      do list with necessary actions specifically tailored to the gestational
      week/labor/delivery is generated. DISCUSSION: Today, with the latest versions of
      Arden Syntax and the application of contemporary software development methods,
      Arden Syntax has become a powerful and versatile medical knowledge representation
      and processing language, well suited to implement a large range of CDSSs,
      including clinical-practice-guideline-based CDSSs. Moreover, such CDS is provided
      and can be shared as a service by different medical institutions, redefining the
      sharing of medical knowledge. Arden Syntax is also highly flexible and provides
      developers the freedom to use up-to-date software design and programming patterns
      for external patient data access.

PMID- 27686852
TI  - Clinical Course of Two Children with Unstable Hemoglobins: The Effect of
      Hydroxyurea Therapy.
AB  - Case reports on the effect of hydroxyurea (HU) therapy for unstable hemoglobins
      (Hbs) are sparse; only three adult cases have been reported. We report for the
      first time on the effect of HU therapy in children carrying unstable Hbs. The
      first case concerns a female child with a familial history of chronic hemolytic
      anemia. She was diagnosed with Hb Volga (HBB: c.83C>A) at the age of 7 months. At
      age 6, treatment options were reconsidered due to increasing fatigue and
      decreasing Hb concentration. The second case also concerns a female child with
      chronic hemolytic anemia and icterus since the age of 5. She was diagnosed with
      Hb Koln (HBB: c.295G>A) at the age of 9. At age 10, treatment options were
      reconsidered due to decreased general condition and poor school performance. Both
      children were started on HU therapy. The child with Hb Volga showed reduced
      clinical symptoms and increased average Hb concentrations. She has been on HU
      therapy for over 7 years at preparation of this manuscript. The child with Hb
      Koln showed decreasing Hb concentrations upon start of therapy; clinical symptoms
      did not improve. Therapy was discontinued after 31/2 months. The Hb Volga case
      report suggests that HU therapy could improve clinical symptoms in some patients
      with unstable Hbs. Based on these and previously published cases, it was
      speculated that response can be predicted by the percentage of Hb F and
      reticulocyte counts.

PMID- 27686853
TI  - Mixed Micelles Loaded with Bile Salt: An Approach to Enhance Intestinal Transport
      of the BCS Class III Drug Cefotaxime in Rats.
AB  - BACKGROUND AND OBJECTIVES: Cefotaxime is a class III drug according to the
      Biopharmaceutical Classification System due to low intestinal permeability based
      on poor oral bioavailability. Bile salt compounds have been shown to be effective
      additive for drug permeation through several biological membranes. The main
      purpose of this study was to investigate the ability of a mixed micelles made of
      phosphatidylcholine, sodium deoxycholate, and loaded with a cefotaxime
      3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate complex to enhance the oral
      bioavailability of cefotaxime in rats. METHODS: Thin-film hydration method was
      used to prepare cefotaxime-loaded mixed micelles using different bile salt
      concentrations (0.87-25 mM of sodium deoxycholate). Overall, micelle sizes
      ranging from 86.9 to 155.6 nm were produced with negative zeta potential values
      from -15.9 to -19.5 mV and drug loading from 10.5 to 18.9 %. The oral
      bioavailability of cefotaxime in mixed micellar formulation was assessed and the
      pharmacokinetic parameters were compared with cefotaxime-3alpha,7alpha-dihydroxy
      12-keto-5beta-cholanate complex and cefotaxime aqueous solution. 24 Male Wistar
      rats were randomly allocated into four groups (n = 6, per group) to receive the
      following: (1) a single intravenous dose of cefotaxime (25 mg/kg) in sterilized
      normal saline solution for injection; (2) a single oral dose of mixed micelles
      (100 mg/kg of cefotaxime) in phosphate buffered saline administered by oral
      gavage; (3) a single oral dose of cefotaxime-3alpha,7alpha-dihydroxy-12-keto
      5beta-cholanate complex (100 mg/kg of cefotaxime) in phosphate buffered saline
      administered by oral gavage; (4) a single oral dose of free cefotaxime (100
      mg/kg) in aqueous solution administered by oral gavage. Blood samples were
      collected for up to 24 h and cefotaxime analyzed using a validated HPLC assay.
      RESULTS: Pharmacokinetic data showed that the oral bioavailability of cefotaxime
      in mixed micelles was found to be 4.91 % higher compared to the cefotaxime in
      aqueous solution (1.30 %). Maximum concentration (C max) of cefotaxime in mixed
      micellar formulation was higher (1.08 +/- 0.1 ug/ml) compared to the cefotaxime
      3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate complex (0.69 +/- 0.1 ug/ml) and
      cefotaxime in aqueous solution (0.52 +/- 0.1 ug/ml). Similarly, the mean values
      for area under the plasma concentration-time curve extrapolated to infinity (AUC0
      infinity) of cefotaxime in the mixed micellar formulation was higher (3.89 +/-
      0.9 MUg.h/mL) compared to the cefotaxime-3alpha,7alpha-dihydroxy-12-keto-5beta
      cholanate complex (1.52 +/- 0.2 MUg.h/mL) and cefotaxime in aqueous solution
      (1.03 +/- 0.4 MUg.h/mL), respectively. CONCLUSION: The mixed micellar formulation
      was able to increase the oral bioavailability of the BCS Class III drug
      cefotaxime up to fourfold by enhancing drug permeation through the mucosal
      membrane of the small intestine.

PMID- 27686854
TI  - Ghrelin and adipose-derived mesenchymal stromal cells improve nerve regeneration
      in a rat model of epsilon-caprolactone conduit reconstruction.
AB  - OBJECTIVE: Attempts have been made to improve nerve conduits in peripheral nerve
      reconstruction. We investigated the potential therapeutic effect of adipose
      derived mesenchymal cells (ASCs) and ghrelin (GHR), a neuropeptide with
      neuroprotective, trophic, and developmental regulatory actions, on peripheral
      nerve regeneration in a model of severe nerve injury repaired with nerve
      conduits. MATERIAL AND METHODS: The right sciatic nerves of 24 male Wistar rats
      were 10-mm transected unilaterally and repaired with Dl-lactic-epsilon
      caprolactone conduits. Rats were then treated locally with saline, ASCs, or GHR.
      At 12 weeks post-surgery, we assessed limb function by measuring ankle stance
      angle and percentage muscle mass reduction and evaluated the histopathology,
      immunohistochemistry, ultrastructure, and morphometry of myelinated fibers. MAIN
      RESULTS: Rats receiving GHR or ASCs showed no significant increased functional
      recovery in ankle stance angle (p=0.372) but a higher nerve area (p=0.015),
      myelin area (p=0.046) and number of myelinated fibers (p=0.012) in the middle and
      distal segments of operated sciatic nerves in comparison to saline-treated
      control animals. CONCLUSION: These results suggest that utilization of ghrelin or
      ASCs may improve nerve regeneration using Dl-lactic-epsilon-caprolactone
      conduits.

PMID- 27686856
TI  - Tunisian tomato by-products, as a potential source of natural bioactive
      compounds.
AB  - Consumption of tomato and tomato products is positively related to the reduction
      in cardiovascular disease and several types of cancer, thanks to the presence of
      natural compounds, such as antioxidants. Peels and seeds fractions of tomato,
      collected after industrial processing in Tunisian industries, were analysed for
      nutritional and antioxidants composition in perspective of its utilisation.
      Proximate composition, fatty acids profile, carotenoids, such as lycopene and
      beta-carotene, polyphenols contents, demonstrated the good potential of these
      residual products as a source of natural compounds, useful for food and
      nutraceuticals applications.

PMID- 27686857
TI  - Ganetespib, an HSP90 inhibitor, kills Epstein-Barr virus (EBV)-infected B and T
      cells and reduces the percentage of EBV-infected cells in the blood.
AB  - HSP90 inhibitors have been shown to kill Epstein-Barr virus (EBV)-infected cells
      by reducing the level of EBV EBNA-1 and/or LMP1. We treated virus-infected cells
      with ganetespib, an HSP90 inhibitor currently being evaluated in multiple
      clinical trials for cancer and found that the drug killed EBV-positive B and T
      cells and reduced the level of both EBV EBNA-1 and LMP1. Treatment of cells with
      ganetespib also reduced the level of pAkt. Ganetespib delayed the onset of EBV
      positive lymphomas and prolonged survival in SCID mice inoculated with one EBV
      transformed B-cell line, but not another B-cell line. The former cell line showed
      lower levels of EBNA-1 after treatment with ganetespib in vitro. Treatment of a
      patient with T-cell chronic active EBV with ganetespib reduced the percentage of
      EBV-positive cells in the peripheral blood. These data indicate that HSP90
      inhibitors may have a role in the therapy of certain EBV-associated diseases.

PMID- 27686858
TI  - Oral hygiene practices and their socio-demographic correlates among Nepalese
      adult: evidence from non communicable diseases risk factors STEPS survey Nepal
      2013.
AB  - BACKGROUND: Oral diseases remain a significant public health problem in Nepal, as
      do oral health behaviours. Socio-demographic factors play a crucial role in
      driving oral hygiene practices. This study aims to identify oral hygiene
      practices and associated socio-demographic factors in Nepalese population.
      METHODS: This descriptive, cross-sectional study recruited 4200 adults (15-69
      years) through multistage cluster sampling. Data obtained from the WHO NCD STEPS
      instrument version 2.2 were analysed in STATA 13.0 using complex sample weighted
      analysis. RESULTS: Prevalence of cleaning teeth at least once a day was 94.9 %
      (95 % CI: 93.7-95.9), while that of cleaning teeth at least twice a day was 9.9 %
      (95 % CI: 8.2-11.9). Use of fluoridated toothpaste was seen among 71.4 % (95 %
      CI: 67.9-74.7) respondents. A 3.9 % (95 % CI: 3.1-5.0) made a dental visit in the
      last 6 months. The 45-69 years age group had lesser odds of cleaning teeth at
      least once a day (AOR: 0.4; 95 % CI: 0.2-0.8), in comparison to 15-29 years age
      group. Women had greater odds of cleaning teeth at least twice a day (AOR: 1.7;
      95 % CI: 1.1-2.4) and having visited a dentist in the last 6 months (AOR: 2.2; 95
      % CI: 1.2-3.8) compared to men. With reference to rural residents, urban
      population had higher odds of using fluoridated toothpaste (AOR: 2.3; 95 % CI:
      1.4-3.4) and making a dental visit within the last 6 months (AOR: 1.9; 95 %
      CI:1.1-3.6). Inhabitants of the Terai had five-fold (AOR: 4.9; 95 % CI: 3.1-7.8)
      greater odds of cleaning teeth once per day than did hill residents. Those with
      higher education had greater odds than non-formal education holders of cleaning
      teeth at least once a day (AOR: 9.0; 95 % CI: 2.9-27.7), cleaning teeth at least
      twice a day (AOR: 5.6; 95 % CI: 2.9-10.6), using fluoridated toothpaste (AOR:
      13.9; 95 % CI: 8.4-23.1), and having visited a dentist in the last 6 months (AOR:
      2.8; 95 % CI: 1.4-5.4). CONCLUSIONS: Cleaning teeth at least once a day is widely
      prevalent in Nepal and a substantial number of population use fluoridated
      toothpaste. However, cleaning teeth twice a day and visiting a dentist is less
      common. Being women, Terai residents, urban residents, and educated were
      significantly associated with oral hygiene practices assessed in this study.

PMID- 27686855
TI  - Synthetic lethality in lung cancer and translation to clinical therapies.
AB  - Lung cancer is a heterogeneous disease consisting of multiple histological
      subtypes each driven by unique genetic alterations. Despite the development of
      targeted therapies that inhibit the oncogenic mutations driving a subset of lung
      cancer cases, there is a paucity of effective treatments for the majority of lung
      cancer patients and new strategies are urgently needed. In recent years, the
      concept of synthetic lethality has been established as an effective approach for
      discovering novel cancer-specific targets as well as a method to improve the
      efficacy of existing drugs which provide partial but insufficient benefits for
      patients. In this review, we discuss the concept of synthetic lethality, the
      various types of synthetic lethal interactions in the context of oncology and the
      approaches used to identify these interactions, including recent advances that
      have transformed the ability to discover novel synthetic lethal combinations on a
      global scale. Lastly, we describe the specific synthetic lethal interactions
      identified in lung cancer to date and explore the pharmacological challenges and
      considerations in translating these discoveries to the clinic.

PMID- 27686859
TI  - Relative efficacy of topical non-steroidal anti-inflammatory drugs and topical
      capsaicin in osteoarthritis: protocol for an individual patient data meta
      analysis.
AB  - BACKGROUND: Pain is the most troubling issue to patients with osteoarthritis
      (OA), yet current pharmacological treatments offer only small-to-moderate pain
      reduction. Current guidelines therefore emphasise the need to identify predictors
      of treatment response. In line with these recommendations, an individual patient
      data (IPD) meta-analysis will be conducted. The study aims to investigate the
      relative treatment effects of topical non-steroidal anti-inflammatory drugs
      (NSAIDs) and topical capsaicin in OA and to identify patient-level predictors of
      treatment response. METHODS: IPD will be collected from randomised controlled
      trials (RCTs) of topical NSAIDs and capsaicin in OA. Multilevel regression
      modelling will be conducted to determine predictors for the specific and the
      overall treatment effect. DISCUSSION: Through the identification of treatment
      responders, this IPD meta-analysis may improve the current understanding of the
      pain mechanisms in OA and guide clinical decision-making. Identifying and
      prescribing the treatment most likely to be beneficial for an individual with OA
      will improve the efficiency of patient management. SYSTEMATIC REVIEW
      REGISTRATION: CRD42016035254.

PMID- 27686860
TI  - The eIF2A knockout mouse.
AB  - Eukaryotic initiation factor 2A (eIF2A) is a 65-kDa protein that was first
      identified in the early 1970s as a factor capable of stimulating initiator
      methionyl-tRNAi (Met-tRNAMeti) binding to 40S ribosomal subunits in vitro.
      However, in contrast to the eIF2, which stimulates Met-tRNAMeti binding to 40S
      ribosomal subunits in a GTP-dependent manner, eIF2A didn't reveal any GTP
      dependence, but instead was found to direct binding of the Met-tRNAMeti to 40S
      ribosomal subunits in a codon-dependent manner. eIF2A appears to be highly
      conserved across eukaryotic species, suggesting conservation of function in
      evolution. The yeast Saccharomyces cerevisae eIF2A null mutant revealed no
      apparent phenotype, however, it was found that in yeast eIF2A functions as a
      suppressor of internal ribosome entry site (IRES)-mediated translation. It was
      thus suggested that eIF2A my act by impinging on the expression of specific
      mRNAs. Subsequent studies in mammalian cell systems implicated eIF2A in non
      canonical (non-AUG-dependent) translation initiation events involving near
      cognate UUG and CUG codons. Yet, the role of eIF2A in cellular functions remains
      largely enigmatic. As a first step toward characterization of the eIF2A function
      in mammalian systems in vivo, we have obtained homozygous eIF2A-total knockout
      (KO) mice, in which a gene trap cassette was inserted between eIF2A exons 1 and 2
      disrupting expression of all exons downstream of the insertion. The KO mice
      strain is viable and to date displays no apparent phenotype. We believe that the
      eIF2A KO mice strain will serve as a valuable tool for researchers studying non
      canonical initiation of translation in vivo.

PMID- 27686861
TI  - A pre-metazoan origin of the CRK gene family and co-opted signaling network.
AB  - CRK and CRKL adapter proteins play essential roles in development and cancer
      through their SRC homology 2 and 3 (SH2 and SH3) domains. To gain insight into
      the origin of their shared functions, we have investigated their evolutionary
      history. We propose a term, crk/crkl ancestral (crka), for orthologs in
      invertebrates before the divergence of CRK and CRKL in the vertebrate ancestor.
      We have isolated two orthologs expressed in the choanoflagellate Monosiga
      brevicollis, a unicellular relative to the metazoans. Consistent with its highly
      conserved three-dimensional structure, the SH2 domain of M. brevicollis crka1 can
      bind to the mammalian CRK/CRKL SH2 binding consensus phospho-YxxP, and to the SRC
      substrate/focal adhesion protein BCAR1 (p130CAS) in the presence of activated
      SRC. These results demonstrate an ancient origin of the CRK/CRKL SH2-target
      recognition specificity. Although BCAR1 orthologs exist only in metazoans as
      identified by an N-terminal SH3 domain, YxxP motifs, and a C-terminal FAT-like
      domain, some pre-metazoan transmembrane proteins include several YxxP repeats in
      their cytosolic region, suggesting that they are remotely related to the BCAR1
      substrate domain. Since the tyrosine kinase SRC also has a pre-metazoan origin,
      co-option of BCAR1-related sequences may have rewired the crka-dependent network
      to mediate adhesion signals in the metazoan ancestor.

PMID- 27686862
TI  - Neural Stem Cell Tumorigenicity and Biodistribution Assessment for Phase I
      Clinical Trial in Parkinson's Disease.
AB  - Human pluripotent stem cells (PSC) have the potential to revolutionize
      regenerative medicine. However undifferentiated PSC can form tumors and strict
      quality control measures and safety studies must be conducted before clinical
      translation. Here we describe preclinical tumorigenicity and biodistribution
      safety studies that were required by the US Food and Drug Administration (FDA)
      and Australian Therapeutic Goods Administration (TGA) prior to conducting a Phase
      I clinical trial evaluating the safety and tolerability of human parthenogenetic
      stem cell derived neural stem cells ISC-hpNSC for treating Parkinson's disease
      (ClinicalTrials.gov Identifier NCT02452723). To mitigate the risk of having
      residual PSC in the final ISC-hpNSC population, we conducted sensitive in vitro
      assays using flow cytometry and qRT-PCR analyses and in vivo assays to determine
      acute toxicity, tumorigenicity and biodistribution. The results from these safety
      studies show the lack of residual undifferentiated PSC, negligible tumorigenic
      potential by ISC-hpNSC and provide additional assurance to their clinical
      application.

PMID- 27686863
TI  - Feralisation targets different genomic loci to domestication in the chicken.
AB  - Feralisation occurs when a domestic population recolonizes the wild, escaping its
      previous restricted environment, and has been considered as the reverse of
      domestication. We have previously shown that Kauai Island's feral chickens are a
      highly variable and admixed population. Here we map selective sweeps in feral
      Kauai chickens using whole-genome sequencing. The detected sweeps were mostly
      unique to feralisation and distinct to those selected for during domestication.
      To ascribe potential phenotypic functions to these genes we utilize a laboratory
      controlled equivalent to the Kauai population-an advanced intercross between Red
      Junglefowl and domestic layer birds that has been used previously for both QTL
      and expression QTL studies. Certain sweep genes exhibit significant correlations
      with comb mass, maternal brooding behaviour and fecundity. Our analyses indicate
      that adaptations to feral and domestic environments involve different genomic
      regions and feral chickens show some evidence of adaptation at genes associated
      with sexual selection and reproduction.

PMID- 27686864
TI  - The impact of P2Y12 promoter DNA methylation on the recurrence of ischemic events
      in Chinese patients with ischemic cerebrovascular disease.
AB  - The primary mechanism of clopidogrel resistance is still unclear. We aimed to
      investigate whether the methylation status of the P2Y12 promoter has effects on
      platelet function and clinical ischemic events. Patients with ischemic
      cerebrovascular disease were enrolled into our study. Venous blood samples were
      drawn for thrombelastograpy (TEG) and active metabolite assay. Patients were
      divided into a case- or control-group based on the occurrence of ischemic events
      during a one year follow-up. Two TEG parameters between the case and control
      groups were statistically significant [ADP inhibition rate (ADP%): P = 0.018; ADP
      induced platelet-fibrin clot strength (MAADP): P = 0.030]. The concentrations of
      clopidogrel active metabolite had no significant difference (P = 0.281). Sixteen
      CpG dinucleotides on P2Y12 promoter were tested. Three CpG sites (CpG11 and CpG12
      + 13) showed lower methylation status, which correlated with a strong association
      with increased risk of clinical events. Changes of MAADP and ADP% were also
      associated with methylation levels of CpG 11 and CpG 12 + 13. Hypomethylation of
      the P2Y12 promoter is associated with a higher platelet reactivity and increased
      risk of ischemic events in our patients. Methylation analysis of peripheral blood
      samples might be a novel molecular marker to help early identification of
      patients at high risk for clinical ischemic events.

PMID- 27686865
TI  - The Architecture of the Cytoplasmic Region of Type III Secretion Systems.
AB  - Type III secretion systems (T3SSs) are essential devices in the virulence of many
      Gram-negative bacterial pathogens. They mediate injection of protein effectors of
      virulence from bacteria into eukaryotic host cells to manipulate them during
      infection. T3SSs involved in virulence (vT3SSs) are evolutionarily related to
      bacterial flagellar protein export apparatuses (fT3SSs), which are essential for
      flagellar assembly and cell motility. The structure of the external and
      transmembrane parts of both fT3SS and vT3SS is increasingly well-defined.
      However, the arrangement of their cytoplasmic and inner membrane export
      apparatuses is much less clear. Here we compare the architecture of the
      cytoplasmic regions of the vT3SSs of Shigella flexneri and the vT3SS and fT3SS of
      Salmonella enterica serovar Typhimurium at ~5 and ~4 nm resolution using electron
      cryotomography and subtomogram averaging. We show that the cytoplasmic regions of
      vT3SSs display conserved six-fold symmetric features including pods, linkers and
      an ATPase complex, while fT3SSs probably only display six-fold symmetry in their
      ATPase region. We also identify other morphological differences between vT3SSs
      and fT3SSs, such as relative disposition of their inner membrane-attached export
      platform, C-ring/pods and ATPase complex. Finally, using classification, we find
      that both types of apparatuses can loose elements of their cytoplasmic region,
      which may therefore be dynamic.

PMID- 27686866
TI  - Ocular adnexal marginal zone lymphoma arising in a patient with IgG4-related
      ophthalmic disease.
AB  - A 41-year-old man was diagnosed with immunoglobulin G4-related disease (IgG4-RD)
      in both eyelids 4 years ago and exhibited good response to steroid therapy.
      However, rapid swelling of the right eyelid lesion was recently observed. As IgG4
      RD progression was suspected, biopsy was performed. Although the histology was
      consistent with IgG4-RD, the infiltrating large atypical lymphoid cells showed
      immunoglobulin light-chain restriction and IgH gene rearrangement. Consequently,
      he was diagnosed with extranodal marginal zone lymphoma with abundant IgG4
      positive cells.

PMID- 27686867
TI  - Copy-number analysis identified new prognostic marker in acute myeloid leukemia.
AB  - Recent advances in genomic technologies have revolutionized acute myeloid
      leukemia (AML) understanding by identifying potential novel actionable genomic
      alterations. Consequently, current risk stratification at diagnosis not only
      relies on cytogenetics, but also on the inclusion of several of these
      abnormalities. Despite this progress, AML remains a heterogeneous and complex
      malignancy with variable response to current therapy. Although copy-number
      alterations (CNAs) are accepted prognostic markers in cancers, large-scale
      genomic studies aiming at identifying specific prognostic CNA-based markers in
      AML are still lacking. Using 367 AML, we identified four recurrent CNA on
      chromosomes 11 and 21 that predicted outcome even after adjusting for standard
      prognostic risk factors and potentially delineated two new subclasses of AML with
      poor prognosis. ERG amplification, the most frequent CNA, was related to
      cytarabine resistance, a cornerstone drug of AML therapy. These findings were
      further validated in The Cancer Genome Atlas data. Our results demonstrate that
      specific CNA are of independent prognostic relevance, and provide new molecular
      information into the genomic basis of AML and cytarabine response. Finally, these
      CNA identified two potential novel risk groups of AML, which when confirmed
      prospectively, may improve the clinical risk stratification and potentially the
      AML outcome.

PMID- 27686869
TI  - Hydrogenation-controlled phase transition on two-dimensional transition metal
      dichalcogenides and their unique physical and catalytic properties.
AB  - Two-dimensional (2D) transition metal dichalcogenides (TMDs) have been widely
      used from nanodevices to energy harvesting/storage because of their tunable
      physical and chemical properties. In this work, we systematically investigate the
      effects of hydrogenation on the structural, electronic, magnetic, and catalytic
      properties of 33 TMDs based on first-principles calculations. We find that the
      stable phases of TMD monolayers can transit from 1T to 2H phase or vice versa
      upon the hydrogenation. We show that the hydrogenation can switch their magnetic
      and electronic states accompanying with the phase transition. The hydrogenation
      can tune the magnetic states of TMDs among non-, ferro, para-, and antiferro
      magnetism and their electronic states among semiconductor, metal, and half-metal.
      We further show that, out of 33 TMD monolayers, 2H-TiS2 has impressive catalytic
      ability comparable to Pt in hydrogen evolution reaction in a wide range of
      hydrogen coverages. Our findings would shed the light on the multi-functional
      applications of TMDs.

PMID- 27686870
TI  - A new C20-diterpenoid alkaloid from the lateral roots of Aconitum carmichaeli.
AB  - A new C20-diterpenoid alkaloid carmichaedine (1) and six known alkaloids (2-7)
      were isolated from the lateral roots of Aconitum carmichaeli. Their structures
      were established on the basis of extensive spectroscopic analyses. Compound 1
      exhibited potent antibacterial activity against Bacillus subtilis with minimum
      inhibitory concentration of 8 MUg/mL.

PMID- 27686868
TI  - Pan-Raf co-operates with PI3K-dependent signalling and critically contributes to
      myeloma cell survival independently of mutated RAS.
AB  - Direct therapeutic targeting of oncogenic RAS is currently still impossible due
      to lack of suitable pharmacological inhibitors. Because specific blockade of
      druggable RAS effectors might represent an alternative treatment approach, we
      evaluated the role of the Raf complex for multiple myeloma (MM) pathobiology. We
      found frequent overexpression of the Raf isoforms (A-, B- and C-Raf) and
      downstream activation of MEK1,2/ERK1,2 in MM cells. Concomitant inhibition of all
      Raf isoforms (pan-Raf inhibition) by RNAi or pharmacological inhibitors was
      required to strongly induce apoptosis in human MM cell lines (HMCLs), in primary
      MM cells in vitro, and in a syngeneic MM mouse model in vivo. The anti-MM effect
      of pan-Raf inhibition did not correlate with the RAS mutation status, and
      functionally appeared to involve both MEK-dependent and -independent mechanisms.
      Furthermore, transcriptome analyses revealed that pan-Raf activity affects PI3K
      dependent signalling, thus highlighting a functional link between the RAS/Raf and
      PI3K/mTOR/Akt pro-survival pathways. Accordingly, pharmacological inhibition of
      PI3K strongly enhanced the anti-MM effect of pan-Raf inhibition in MM cell lines
      and in primary MM cells in vitro and in vivo. Concomitant pan-Raf/PI3K inhibition
      was also effective in carfilzomib- and lenalidomide-resistant MM models
      underscoring that this attractive therapeutic anti-MM strategy is suitable for
      immediate clinical translation.

PMID- 27686871
TI  - Role of the Internet in Care Initiation by People Living With HIV.
AB  - People frequently use the internet to obtain information, including information
      about health, but we lack understanding of how people living with HIV (PLHIV) use
      the internet in their care and treatment decisions. In this secondary analysis,
      interviews with 23 individuals who initiated HIV care at an urban, Midwestern
      medical center and mentioned internet use were analyzed using qualitative content
      analysis to explore how they used the internet during the process of initiating
      HIV care. HIV care had been initiated by this sample from less than one month to
      three years post-diagnosis. Participants discussed the internet as a source of
      information about their diagnosis that influenced their care and treatment
      decisions. Five themes were predominant: (i) The internet alerted me to the
      possibility of HIV, (ii) the internet showed me a solution is available, (iii)
      the internet influenced my decisions about care, (iv) the internet empowered me
      to participate in my treatment decisions, and (v) the internet gave me hope for
      my future. The results suggest that the internet has the potential to provide
      information that can profoundly influence PLHIVs' acceptance of care and
      treatment decisions. Clinicians face a new reality in which patients use internet
      resources to obtain information and shape opinions about HIV treatment and care
      initiation decision-making. Guiding PLHIV in their selection of online resources
      is one approach to educating and empowering individuals as they cope with their
      diagnosis and contemplate decisions regarding HIV care and treatment. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27686873
TI  - Protocatechuic Acid: Inhibition of Fibril Formation, Destabilization of Preformed
      Fibrils of Amyloid-beta and alpha-Synuclein, and Neuroprotection.
AB  - Protocatechuic acid (PCA) is the major metabolite of the anthocyanin known as
      cyanidin 3-glucoside. It is found in plasma and tissues, such as the brain,
      heart, liver, and kidneys, following consumption of a rich source of this
      flavonoid. The abnormal pathological assembly of amyloid-beta (Abeta) and alpha
      synuclein (alphaS) is an underlying mechanism involved in the formation of
      amyloid plaques and Lewy bodies in the brain, which are responsible for
      neuropathology symptoms in Alzheimer's (AD) and Parkinson's diseases (PD),
      respectively. This research was performed to evaluate the protective effects of
      PCA, by establishing its potential role in inhibiting aggregation and fibril
      destabilization of Abeta and alphaS proteins. It has been found that PCA inhibits
      the aggregation of Abeta and alphaS and destabilizes their preformed fibrils.
      These results were confirmed by TEM images, electrophoresis, and immunoblotting
      experiments. Furthermore, PCA prevents the death of PC12 cells triggered by Abeta
      and alphaS-induced toxicity.

PMID- 27686872
TI  - Delayed Implants Outcome in Maxillary Molar Region.
AB  - BACKGROUND: The aim of the present study was to assess bone volume changes in
      maxillary molar regions after delayed implants placement. MATERIALS AND METHODS:
      Patients presented large bone defects after tooth extractions. Reactive soft
      tissue was left into the defects. No grafts were used. Cone beam computed
      tomography (CBCT) scans were performed before tooth extractions, at implant
      placement (at 3 months from extraction) and 3 years after implant placement, bone
      volume measurements were assessed. RESULTS: Bucco-lingual width showed a
      statistically significant decrease (p = .013) at implant placement, 3 months
      after extraction. Moreover, a statistically significant increase (p < .01) was
      measured 3 years after implant placement. No statistically significant
      differences (p > .05) were found between baseline values (before extraction) and
      at 3 years from implant placement. Vertical dimension showed no statistically
      significant differences (p > .05) at implant placement, 3 months after
      extraction. Statistically significant differences (p < .0001) were found between
      baseline values (before extraction) and at 3 months from implant placement as
      well as between implant placement values and 3 years later. CONCLUSION: CT scans
      presented successful outcome of delayed implants placed in large bone defects at
      3-year follow-up.

PMID- 27686874
TI  - Screening patients for communication difficulty: The diagnostic accuracy of the
      IFCI staff questionnaire.
AB  - PURPOSE: Many patients have difficulty communicating about their healthcare. At
      present there is no tool to identify these patients. This research investigated
      whether the Inpatient Functional Communication Interview Staff Questionnaire
      (IFCI SQ) could detect patients who have difficulty communicating their
      healthcare needs by investigating the sensitivity, specificity and internal
      consistency of the IFCI SQ. METHOD: Fifty patients and their nurses participated
      in this research. Every second consecutive admission on the general medical ward
      of a hospital was assessed for communication difficulty by a speech-language
      pathologist on the IFCI and screened for communication difficulty by a nurse
      using the IFCI SQ. RESULT: At a cut off score of <2, the IFCI SQ had a
      sensitivity of 95% and a specificity of 77% compared with the IFCI. The IFCI SQ
      is a useful test in identifying patients who have communication difficulty and is
      an extremely good test at ruling out patients who do not have communication
      difficulty. The internal consistency of the IFCI SQ was also high at 0.954.
      CONCLUSION: The IFCI SQ is a promising tool to detect patients in hospital with
      communication difficulty. Further research is required to explore the
      psychometric properties of the IFCI SQ in more detail.

PMID- 27686875
TI  - UNderstanding uptake of Immunisations in TravellIng aNd Gypsy communities
      (UNITING): a qualitative interview study.
AB  - BACKGROUND: Gypsies, Travellers and Roma (referred to as Travellers) are less
      likely to access health services, including immunisation. To improve immunisation
      rates, we need to understand what helps and hinders individuals in these
      communities in taking up immunisations. AIMS: (1) Investigate the barriers to and
      facilitators of acceptability and uptake of immunisations among six Traveller
      communities across four UK cities; and (2) identify possible interventions to
      increase uptake of immunisations in these Traveller communities that could be
      tested in a subsequent feasibility study. METHODS: Three-phase qualitative study
      underpinned by the social ecological model. Phase 1: interviews with 174
      Travellers from six communities: Romanian Roma (Bristol); English Gypsy/Irish
      Traveller (Bristol); English Gypsy (York); Romanian/Slovakian Roma (Glasgow);
      Scottish Showpeople (Glasgow); and Irish Traveller (London). Focus on childhood
      and adult vaccines. Phase 2: interviews with 39 service providers. Data were
      analysed using the framework approach. Interventions were identified using a
      modified intervention mapping approach. Phase 3: 51 Travellers and 25 service
      providers attended workshops and produced a prioritised list of potentially
      acceptable and feasible interventions. RESULTS: There were many common accounts
      of barriers and facilitators across communities, particularly across the English
      speaking communities. Scottish Showpeople were the most similar to the general
      population. Roma communities experienced additional barriers of language and
      being in a new country. Men, women and service providers described similar
      barriers and facilitators. There was widespread acceptance of childhood and adult
      immunisation, with current parents perceived as more positive than their elders.
      A minority of English-speaking Travellers worried about multiple/combined
      childhood vaccines, adult flu and whooping cough. Cultural concerns about
      vaccines offered during pregnancy and about human papillomavirus were most
      evident in the Bristol English Gypsy/Irish Traveller community. Language,
      literacy, discrimination, poor school attendance, poverty and housing were
      identified by Travellers and service providers as barriers for some. Trustful
      relationships with health professionals were important and continuity of care was
      valued. A few English-speaking Travellers described problems of booking and
      attending for immunisation. Service providers tailored their approach to
      Travellers, particularly the Roma. Funding cuts, NHS reforms and poor monitoring
      challenged their work. Five 'top-priority' interventions were agreed across
      communities and service providers to improve the immunisation among Travellers
      who are housed or settled on an authorised site: (1) cultural competence training
      for health professionals and frontline staff; (2) identification of Travellers in
      health records to tailor support and monitor uptake; (3) provision of a named
      frontline person in general practitioner practices to provide respectful and
      supportive service; (4) flexible and diverse systems for booking appointments,
      recall and reminders; and (5) protected funding for health visitors specialising
      in Traveller health, including immunisation. LIMITATIONS: No Travellers living on
      the roadside or on unofficial encampments were interviewed. We should exert
      caution in generalising to these groups. FUTURE WORK: To include development,
      implementation and evaluation of a national policy plan (and practice guidance
      plan) to promote the uptake of immunisation among Traveller communities. STUDY
      REGISTRATION: Current Controlled Trials ISRCTN20019630 and UK Clinical Research
      Network Portfolio number 15182. FUNDING: This project was funded by the National
      Institute for Health Research (NIHR) Health Technology Assessment programme and
      will be published in full in Health Technology Assessment; Vol. 20, No. 72. See
      the NIHR Journals Library website for further project information.

PMID- 27686877
TI  - 'Many die in the hurricane': An Interpretative Phenomenological Analysis of
      Adults with Psychosis and a History of Childhood Physical Abuse.
AB  - The study aimed to investigate the experience of adults with a diagnosis of
      psychosis and who have survived childhood physical abuse. We interviewed eight
      participants and used interpretative phenomenological analysis to generate
      themes. The main themes were of perceiving an everyday world of aggression and
      contempt by others, pervasive mistrust, feeling isolated and for some, attacking
      oneself with hate. Most participants were also able to reflect on what they saw
      as 'paranoia' or 'voices'. Paranoia was described as a fluctuating compulsive
      'thread' of meaning, feeling and sometimes a transformation of the self. The
      paranoia and voices experienced often involved a dread of murderous obliteration.
      The discussion considers the relevance of altered consciousness, psychotic states
      of self and the contribution of mutating narrative and meaning. Our findings
      point to the importance of therapy for interpersonal difficulties and the long
      term effects of trauma. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27686876
TI  - Chemotherapy reaction induced by ixabepilone, a microtubule stabilizing agent,
      mimicking extramammary Paget's disease in a patient with breast carcinoma.
AB  - The histopathologic characteristics of reactions caused by the many novel
      anticancer agents are under-recognized. We report a case of a 67-year-old female
      with locally advanced metastatic breast cancer, who initially presented with an
      extensive reticulated erythematous patch on the trunk caused by intravascular
      metastases confirmed by a skin biopsy. Owing to disease progression, she was
      started on ixabepilone, a mitotic inhibitor. While receiving ixabepilone, another
      skin biopsy was obtained and initially interpreted as extramammary Paget's
      disease. However, the biopsy showed metaphase arrest of numerous keratinocytes in
      the basilar and suprabasilar epidermis. Atypical epithelial cells were only
      present in the intravascular spaces similar to the initial biopsy. Given the
      temporal association between the initiation of ixabepilone therapy and the
      epidermal mitotic arrest, a diagnosis of chemotherapy reaction to ixabepilone was
      rendered. Ixabepilone is an analog of epothilone, a microtubule stabilizer
      causing mitotic arrest of the cell cycle approved for the treatment of metastatic
      and locally advanced treatment-resistant breast cancer. The demonstration of
      epidermal mitotic arrest caused by ixabepilone is without precedent. The case
      emphasizes the importance of considering a chemotherapy reaction in the
      histologic differential diagnosis of epidermal mitotic arrest in a cancer patient
      receiving chemotherapy.

PMID- 27686878
TI  - Community Health Needs Assessments: Expanding the Boundaries of Nursing Education
      in Population Health.
AB  - BACKGROUND: Conducting federally mandated community health needs assessments
      through academic-practice partnerships provides new opportunities for developing
      population health nursing competencies. OBJECTIVES: The purpose of this article
      was to describe how a baccalaureate practicum experience within such an
      assessment process, involving health care system partners, re-affirms the
      importance of community and population health assessment in the development of
      future nursing leaders. RESULTS: Student evaluations indicated an emerging
      appreciation for the social determinants of health, the power of partnerships,
      and the importance of diversity. Integrating health care and public health system
      perspectives on assessment meets both public health and nursing accreditation
      standards and extends student leadership experiences. Such integration also
      improves regional capacity for improving population health. CONCLUSIONS: Federal
      mandates for community health needs assessments provide opportunities to advance
      leadership roles for nursing graduates throughout the health care system, and for
      confirming the importance of community assessment as an essential nursing
      competency.

PMID- 27686879
TI  - Evaluation of conservative approach in the management of ureteroenteric
      strictures following radical cystectomy with Bricker ileal conduit: a single
      center experience.
AB  - OBJECTIVE: The aim of this study was to evaluate the risk factors and treatment
      options for ureteroenteric strictures (UES) following radical cystectomy (RC) and
      ileal conduit (IC) formation, and specifically to comment on the conservative
      management of UES in asymptomatic patients. MATERIALS AND METHODS: The datasheets
      were reviewed of 304 consecutive patients who were treated with an RC and IC
      between January 2001 and May 2011 in a Belgian tertiary center and who followed a
      strict follow-up protocol. Long-term treatment outcomes were retrospectively
      analyzed. RESULTS: Twenty-two patients (7.2%) were diagnosed with UES (affecting
      27 ureters in total), when a new-onset hydroureteronephrosis or increase of the
      pre-existing hydroureteronephrosis was detected by ultrasound or computed
      tomography. A retrograde loopogram was then performed to confirm the UES. The
      mean follow-up time was 33 months. A decline in renal function, the presence of
      flank pain and urinary tract infections were indications for interventional
      treatment. Six patients underwent double-J stent placement, two patients received
      percutaneous nephrostomies as a definitive treatment and two patients underwent
      ureterointestinal reimplantation. Asymptomatic patients with a UES and a
      favorable renal function were conservatively managed. They remained asymptomatic
      during follow-up and required no active treatment. CONCLUSIONS: No clinical
      variable was independently associated with an increased risk of UES. These long
      term data suggest that a selected patient population of asymptomatic patients
      with good renal function at the time of UES diagnosis can be safely managed
      conservatively.

PMID- 27686880
TI  - Combination of preoperative NLR, PLR and CEA could increase the diagnostic
      efficacy for I-III stage CRC.
AB  - BACKGROUND: Inflammation plays an important role in the development and
      progression of CRC. The members of inflammatory biomarkers, preoperative NLR and
      PLR, have been proved by numerous studies to be promising prognostic biomarkers
      for CRC. However, the diagnostic value of the two biomarkers in CRC remains
      unknown, and no study reported the combined diagnostic efficacy of NLR, PLR and
      CEA. METHODS: Five hundred and fifty-nine patients with I-III stage CRC
      undergoing surgical resection and 559 gender- and age-matched healthy controls
      were enrolled in this retrospective study. NLR and PLR were calculated from
      preoperative peripheral blood cell count detected using white blood cell five
      classification by Sysmex XT-1800i Automated Hematology System and serum CEA were
      measured by electrochemiluminescence by ELECSYS 2010. The diagnostic performance
      of NLR, PLR and CEA for CRC was evaluated by ROC curve. RESULTS: Levels of NLR
      and PLR in the cases were significantly higher than them in the healthy controls.
      ROC curves comparison analyses showed that the diagnostic efficacy of NLR
      (AUC=.755, 95%CI=.728-.780) alone for CRC was significantly higher than PLR
      (AUC=.723, 95%CI=.696-.749, P=.037) and CEA (AUC=.690, 95%CI=.662-.717, P=.002)
      alone. In addition, the diagnostic efficacy of the combination of NLR, PLR and
      CEA(AUC=.831, 95%CI=.807-.852)for CRC was not only significantly higher than NLR
      alone but also higher than any combinations of the two of these three biomarkers
      (P<.05). Moreover, the NLR and PLR in the patients with TNM stage I/II was higher
      than that in the healthy controls, and patients with stage III had a higher NLR
      and PLR than those with stage I/II, but no significant difference was observed.
      CONCLUSION: Our study indicated that preoperative NLR could be a CRC diagnostic
      biomarker, even for early stage CRC, and the combination of NLR, PLR and CEA
      could significantly improve the diagnostic efficacy.

PMID- 27686881
TI  - The effects of anxiety and depression on in vitro fertilisation outcomes of
      infertile Chinese women.
AB  - The object was to assess anxiety and depression during in vitro fertilisation
      (IVF) treatment and determine IVF-related psychological factors in infertile
      Chinese women. The self-rating anxiety scale (SAS) and self-rating depression
      scale (SDS) were used to evaluate anxiety and depression among 842 patients,
      respectively. A univariate analysis was used to compare variables among three SAS
      groups and three SDS groups. Anxiety and depression were both represented in
      21.3% of the cases. Patients <35 years tended to be more anxious. In women <35
      years, the SDS scores were higher with lower educational backgrounds and female
      or couple's infertility, while the SAS scores were higher in female or couple's
      infertility. In older ones, the SDS scores were higher in those with lower
      educational backgrounds and longer time for infertility, while the SAS scores
      were higher in those with lower educational backgrounds. In SAS groups 1-3, the
      embryo availability was 5.0 (3.0-8.0), 5.0 (3.0-8.0), and 3.0 (2.0-4.5) (p =
      .013); and the fertilisation rate was 91.9, 90.4, and 81.8% (p < .001),
      respectively. We concluded that infertile women experience anxiety and depression
      during IVF treatment, especially in women <35 years. Younger women with female
      infertility would be more anxious and depressive while higher education can
      protect them from depression. In older ones, they would experience more
      depressive with longer time for infertility and be less anxious and depressive
      with higher education. Anxiety affects the fertilisation rate and embryo
      availability.

PMID- 27686882
TI  - Determination of an optimally sensitive and specific chemical exchange saturation
      transfer MRI quantification metric in relevant biological phantoms.
AB  - The purpose of this study was to develop realistic phantom models of the
      intracellular environment of metastatic breast tumour and naive brain, and using
      these models determine an analysis metric for quantification of CEST MRI data
      that is sensitive to only labile proton exchange rate and concentration. The
      ability of the optimal metric to quantify pH differences in the phantoms was also
      evaluated. Novel phantom models were produced, by adding perchloric acid extracts
      of either metastatic mouse breast carcinoma cells or healthy mouse brain to
      bovine serum albumin. The phantom model was validated using 1 H NMR spectroscopy,
      then utilized to determine the sensitivity of CEST MRI to changes in pH, labile
      proton concentration, T1 time and T2 time; six different CEST MRI analysis
      metrics (MTRasym , APT*, MTRRex , AREX and CESTR* with and without T1 /T2
      compensation) were compared. The new phantom models were highly representative of
      the in vivo intracellular environment of both tumour and brain tissue. Of the
      analysis methods compared, CESTR* with T1 and T2 time compensation was optimally
      specific to changes in the CEST effect (i.e. minimal contamination from T1 or T2
      variation). In phantoms with identical protein concentrations, pH differences
      between phantoms could be quantified with a mean accuracy of 0.6 pH units. We
      propose that CESTR* with T1 and T2 time compensation is the optimal analysis
      method for these phantoms. Analysis of CEST MRI data with T1 /T2 time compensated
      CESTR* is reproducible between phantoms, and its application in vivo may resolve
      the intracellular alkalosis associated with breast cancer brain metastases
      without the need for exogenous contrast agents.

PMID- 27686883
TI  - Patterns of sexual behaviour and sexual healthcare needs among transgender
      individuals in Melbourne, Australia, 2011-2014.
AB  - OBJECTIVE: Literature surrounding the healthcare needs of transgender individuals
      is limited in Australia. This study aimed to investigate the demographic
      characteristics, risk behaviours and HIV/STI positivity among male-to-female
      (MTF) and female-to-male (FTM) transgender individuals attending Melbourne Sexual
      Health Centre (MSHC), Australia, between 2011 and 2014. METHOD: A retrospective
      cohort analysis for 133 transgender individuals was conducted based on the first
      visit of individuals to MSHC during the study period. Demographic
      characteristics, sexual behaviours and HIV/STI positivity were examined. RESULTS:
      The majority of transgender individuals were single or never married (74%; n=99).
      Almost half of the individuals (47%; n=62) had ever engaged in sex work during
      their lifetime. The median number of male sexual partners (MSP) reported in the
      last 3 months was 1 (IQR: 1-2) and with female sexual partners (FSP) was 2 (IQR:
      1-4). For those who reported having sexual partners in the previous 3 months,
      always using condoms with MSP was 31% (n=22), and that with FSP was 18% (n=2).
      HIV/STI positivity during the study period was 7% (n=8) for chlamydia, 5% (n=6)
      for gonorrhoea, 5% (n=5) for syphilis and 1% (n=1) for HIV. Hormone use for
      reassignment was reported by 63% (n=90) of individuals and reassignment surgery
      was reported by 27% (n=29+6=35). CONCLUSIONS: Transgender individuals in this
      study were found to be a diverse group, with a history of sex work being a common
      feature. These findings indicate that transgender individuals' sexual healthcare
      needs differ substantially from those in other countries, including the US and
      Canada. Attention to differences in MTF and FTM transgender persons must be
      considered in healthcare settings in Australia.

PMID- 27686885
TI  - Reanalysis of PACE trial reignites row over chronic fatigue treatment.

PMID- 27686884
TI  - Trichomonas vaginalis infection is uncommon in the British general population:
      implications for clinical testing and public health screening.
AB  - INTRODUCTION: Variable use of new molecular assays, asymptomatic infections and a
      lack of population data mean that the population burden of Trichomonas vaginalis
      is uncertain. We investigated the age-specific prevalence of T. vaginalis within
      the sexually active British general population to inform testing strategies.
      METHODS: Britain's third National Survey of Sexual Attitudes and Lifestyle
      (Natsal-3) is a probability sample survey of 15 162 individuals aged 16-74 years,
      undertaken during 2010-2012. Urine from 4386 participants aged 16-44 years
      reporting >=1 lifetime sexual partner was tested for T. vaginalis using in-house
      real-time PCR. RESULTS: Urinary T. vaginalis was detected in seven women and no
      men providing urine samples, giving a weighted prevalence estimate of 0.3% (95%
      CI 0.1% to 0.5%) in sexually experienced women aged 16-44 years. Of the seven
      women with T. vaginalis detected, four were of black or mixed ethnicity
      (prevalence 2.7% (0.9% to 7.7%) in this group) and five reported recent partners
      of black or mixed ethnicity. Six of the women reported symptoms, and five
      reported sexual health clinic attendance in the past 5 years (prevalence in those
      reporting clinic attendance: 1.0% (0.4% to 2.3%)). The prevalence of a self
      reported history of T. vaginalis (past 5 years) was 0.1% (0.0% to 0.2%) in women
      and 0.0% (0.0% to 0.2%) in men aged 16-44 years. CONCLUSIONS: Our British
      population prevalence estimates indicate that T. vaginalis is a rare infection.
      These data support policies that restrict asymptomatic screening for T. vaginalis
      and suggest deployment of molecular tests should be focused within clinical
      settings and guided by symptoms and local demography.

PMID- 27686886
TI  - Neuroprotective Effects of Cannabidiol in Hypoxic Ischemic Insult. The
      Therapeutic Window in Newborn Mice.
AB  - BACKGROUND: A relevant therapeutic time window (TTW) is an important criterion
      for considering the clinical relevance of a substance preventing newborn hypoxic
      ischemic (HI) brain damage. OBJECTIVE: To test the TTW of the neuroprotective
      effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn
      HI brain damage. METHOD: 9-10 day-old C57BL6 mice underwent a HI insult (10%
      oxygen for 90 min after left carotid artery electrocoagulation). Then, CBD 1
      mg/kg or vehicle were administered s.c. 15 min, or 1, 3, 6, 12, 18 or 24 h after
      the end of the HI insult. Seven days later brain damage was assessed using T2W
      Magnetic Resonance Imaging scan (ipsilateral hemisphere volume loss, IVHL) and
      histological studies: Nissl staining (neuropathological score), TUNEL staining
      (apoptotic damage) and immunohistochemistry with glial fibrillary acidic protein
      (astrocyte viability) or ionized calcium binding adaptor molecule (microglial
      activation). RESULTS: CBD administered up to 18 h after HI reduced IHVL and
      neuropathological score by 60%, TUNEL+ count by 90% and astrocyte damage by 50%.
      In addition, CBD blunted the HI-induced increase in microglial population. When
      CBD administration was delayed 24 h, however, the neuroprotective effect was lost
      in terms of IHVL, apoptosis or astrogliosis reduction. CONCLUSION: CBD shows a
      TTW of 18 h when administered to HI newborn mice, which represents a broader TTW
      than reported for other neuroprotective treatments including hypothermia.

PMID- 27686887
TI  - Enhancing Social Responsibility and Prosocial Leadership to Prevent Aggression,
      Peer Victimization, and Emotional Problems in Elementary School Children.
AB  - Testing the theories that form the basis of prevention programs can enhance our
      understanding of behavioral change and inform the development, coordination, and
      adaptation of prevention programs. However, theories of change showing the
      linkages from intervention program components to risk or protective factors to
      desired outcomes across time are rarely specified or tested. In this 2-year
      longitudinal study, we test the theory that increases in two protective factors
      (i.e., children's prosocial leadership and their teachers' expectations of social
      responsibility) targeted by the WITS Programs (Walk Away, Ignore, Talk it Out,
      and Seek Help) would be associated with declines in peer victimization,
      aggression, and emotional problems. Participants included Canadian students, in
      grades 1-4 at baseline (n = 1329) and their parents and teachers. Consistent with
      our theory of change, variability in program implementation (adherence and
      integration) and in children's use of program skills (child responsiveness) are
      related to increases in both protective factors. Increases in these protective
      factors are associated with subsequent declines in children's aggression,
      victimization, and emotional problems. We discuss how enhancement of these
      protective factors may operate to improve child outcomes and the need for theory
      based research to refine and improve the effectiveness of intervention strategies
      and to improve program scale-up.

PMID- 27686888
TI  - Role of lasers as an adjunct to scaling and root planing in patients with type 2
      diabetes mellitus: a systematic review.
AB  - The aim of the study was to assess the efficacy of adjunctive use of laser
      therapy (LT) alone or antimicrobial photodynamic therapy (aPDT) to improve
      clinical periodontal and HbA1c levels in patients with both chronic periodontitis
      (CP) and type 2 diabetes mellitus (T2DM). Electronic search of the MEDLINE,
      PubMed, EMBASE, Science Direct, and SCOPUS databases were combined with hand
      searching of articles published from 1975 up to and including March 2016 using
      relevant MeSH terms. Six studies were selected for this review. In these six
      studies, laser treatment was applied, after scaling and root planing (SRP), in
      two ways: Three studies used laser alone and three studies used laser with
      photosensitizer. All the six included studies reporting clinical periodontal and
      glycemic parameters showed that LT and aPDT were effective in the treatment of CP
      in T2DM subjects at follow-up. Two studies showed significantly better
      periodontal outcomes for LT as an adjunct to SRP as compared to SRP alone,
      whereas four studies showed comparable periodontal outcomes among adjunctive LT
      or aPDT with SRP. Two studies showed significant reduction of HbA1c levels in LT
      and aPDT as compared to SRP, whereas three studies showed comparable percentage
      levels at follow-up. It remains debatable whether LT or aPDT as adjunct to SRP is
      more effective as compared to SRP alone in the improvement of clinical
      periodontal and glycemic control in patients with both CP and T2DM, given that
      the scientific evidence is weak.

PMID- 27686889
TI  - Treatment outcome of vocal cord leukoplakia by transoral laser microsurgery.
AB  - The aim of this study is to evaluate the treatment outcome and analyze the
      associated factors of postoperative recurrence in patients who received transoral
      laser microsurgery for vocal cord leukoplakia. The demographic, histopathological
      data were retrospectively reviewed and the factors associated with recurrence of
      vocal leukoplakia after surgery were analyzed statistically. A total of 44
      patients, including 36 males and 8 females, with a mean age of 50.4 +/- 13.4
      years, were enrolled. All the patients received excision of the vocal leukoplakia
      by carbon dioxide laser (2-4 Watt, ultrapulse mode) under general anesthesia. No
      patients had malignant transformation after surgery. Postoperative recurrence
      occurred in 10 patients (22.7 %). Univariate analysis showed that patients who
      had the habit of cigarette smoking, alcohol drinking, and presence of
      gastroesophageal reflux disease tended to recur. Among these risk factors,
      presence of gastroesophageal reflux disease (odds ratio 8.43) was the independent
      prognostic factor for recurrence using multivariate logistic regression analysis.
      Carbon dioxide laser excision is effective for treating vocal leukoplakia that is
      still confined to dysplasia of any degree, with acceptable morbidity. This study
      suggests that the presence of gastroesophageal reflux disease is the prognostic
      indicator for postoperative recurrence of vocal leukoplakia. Aggressive treatment
      of reflux disease for those who have received surgical excision for vocal
      leukoplakia is indicated.

PMID- 27686891
TI  - Senior staff need more support to stay in post.
AB  - Every year, Nursing Management's sister publication Nursing Standard conducts a
      survey of nurse directors in the NHS. This year's results (analysis, page 8 )
      reveal that turnover at this executive level remains worryingly high. They show
      that 132 chief nurses at 230 English trusts, 14 Scottish and seven Welsh health
      boards have been in post only since 2014, and 33 stepped into the role just this
      year.

PMID- 27686892
TI  - A new approach to end of life care.
AB  - A palliative care charity has devised a new approach to end of life care based on
      the Human Rights Act.

PMID- 27686893
TI  - Thousands of former nurses urged to return to profession.
AB  - Letters have been sent to tens of thousands of former practising nurses in
      England urging them to return to the profession.

PMID- 27686890
TI  - Treatment of periorbital wrinkles using multipolar fractional radiofrequency in
      Korean patients.
AB  - A limited number of studies have evaluated the efficacy and safety of electrode
      pin fractional radiofrequency (FRF) for periorbital wrinkle treatment in Asian
      patients, but none have measured noninvasive methodological objective parameters
      such as periorbital wrinkle area. This study aimed to investigate the efficacy
      and safety of electrode pin multipolar FRF for the improvement of periorbital
      wrinkles in Korean patients by using a noninvasive methodological objective
      parameter. Seventy female subjects with periorbital wrinkles (age range, 40-60
      years) participated in this study. Each patient underwent three sessions of FRF
      treatment to the periorbital region separated by 2-week intervals. The area of
      periorbital wrinkles was analyzed by using a Robo Skin Analyzer CS50 at 4 weeks
      after the final treatment session. Periorbital wrinkle area was significantly
      decreased at 1-month follow-up (75.77 +/- 29.46 mm2) compared to baseline (94.74
      +/- 31.62 mm2). The improvement ratio of periorbital wrinkle area was 20.02 %.
      Side effects were limited to transient mild erythema, swelling, and crusts. Pain
      was tolerable without local anesthesia. Our findings suggest that the multipolar
      electrode pin FRF can be an effective and safe method for reducing periorbital
      wrinkles in Asian patients.

PMID- 27686894
TI  - Senior nurses appointed to NHS Improvement.
AB  - Two senior nurses have been appointed to new positions at NHS Improvement, where
      they will work as deputies to executive director of nursing Ruth May.

PMID- 27686895
TI  - Too few midwives following Brexit.
AB  - There could be a 'huge' shortage of midwives in England if professionals from
      other European Union countries cannot work in the NHS after Brexit, the Royal
      College of Midwives (RCM) predicts.

PMID- 27686897
TI  - King's Fund records 6 million A&E attendances.
AB  - Relentless demand for services is driving up waiting times and exacerbating
      financial pressure on the NHS, according to a report from The King's Fund.

PMID- 27686898
TI  - Trusts are struggling to retain chief nurses.
AB  - An analysis of 230 English NHS trusts, 14 Scottish and seven Welsh health boards
      found 132 (53%) chief nurses had only been in post since 2014. Of this figure, 33
      nurse directors took up their new positions this year.

PMID- 27686899
TI  - Revalidation reflection.
AB  - With the Nursing and Midwifery Council's (NMC) new revalidation requirements
      firmly in place, readers may be interested in some advice on written reflections.

PMID- 27686900
TI  - Guide for clinical audit leads.
AB  - All NHS trusts must manage the conduct of clinical audits to ensure any
      highlighted problems are managed effectively. Most trusts appoint clinicians as
      clinical audit leads (CALs) for services, directorates or specialties, so those
      who have, or who are considering taking on, a CAL role may be interested in the
      Healthcare Quality Improvement Partnership's new guide.

PMID- 27686901
TI  - Dementia evidence.
AB  - Modelling Outcome and Cost Impacts of Interventions for Dementia is a dementia
      evidence toolkit for commissioners, care providers, health and care professionals
      and people with dementia and their families.

PMID- 27686902
TI  - National health snapshot.
AB  - An online tool containing the most up-to-date and accurate data on the health of
      the people of Wales has been launched by the Health Intelligence Division. The
      aim is to encourage government, public services, healthcare professionals and
      private and voluntary sector organisations to improve people's health and well
      being in their areas.

PMID- 27686903
TI  - Managing demand for care.
AB  - The NHS is facing unprecedented demand for elective care, according to NHS
      England, and there is a need to manage this demand to ensure that only the most
      appropriate cases are referred for face-to-face consultation or hospital
      admission.

PMID- 27686904
TI  - Around the world.
AB  - 1. Childhood and Adolescent Obesity 24-26 October, Ottawa, Ontario, Canada
      tinyurl.com/conference-obesity.

PMID- 27686905
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27686906
TI  - Our Commitment to You for End of Life Care.
AB  - Essential facts In July the government announced a new commitment to improve end
      of life care in England in response to What's Important to Me: A Review of Choice
      in End of Life Care (the Choice Review).

PMID- 27686907
TI  - Signs of moral distress in nursing practice.
AB  - Healthcare is in a turbulent place as society expects nurses to remain clinically
      robust while adapting to changes. That such changes have the potential to
      undermine care quality or nurses' health is too often a secondary consideration (
      RCN 2013 ).

PMID- 27686908
TI  - We need compassion through listening.
AB  - 'To find grace, watch a 16-year-old carer feed an 85-year-old woman with severe
      dementia, but pass by those in the office writing care plans' ( Barritt 2005 ).

PMID- 27686909
TI  - From Twitter.
AB  - Nurses on Twitter.

PMID- 27686910
TI  - Forest: Stay Focused.
AB  - Did you know that one sixth of smartphone owners check their mobile devices 50
      times a day? If that sounds like something you do, try the Forest app.

PMID- 27686911
TI  - Embracing the care home challenge.
AB  - 'I thought I knew everything, but I have discovered a whole new world. Working in
      a care home is challenging, but so rewarding.' This was the confession of a care
      home manager who moved to the sector 3 years ago, after working for 28 years in
      the NHS. She was speaking at an event titled Independent and Third Sector Care is
      NOT a Fringe Business, which was organised by the RCN Scotland Board at congress
      earlier this year.

PMID- 27686912
TI  - Looking at advanced practice nursing roles.
AB  - The development of advanced practice nursing roles in primary care is becoming
      popular in many countries and a recent study across 39 nations confirms this
      trend ( Maier and Aiken 2016 ).

PMID- 27686915
TI  - How to succeed at the confirmer stage.
AB  - What is the role of the confirmer? There is a lot of anxiety from nurses about
      being a confirmer, but the process is actually much less daunting when you go
      through it.

PMID- 27686916
TI  - A real-time Excel-based scheduling solution for nursing staff reallocation.
AB  - Aim This article describes the development and testing of an Excel-based
      scheduling solution for the flexible allocation and reallocation of nurses to
      cover sudden, unplanned absences among permanent nursing staff. Method A quasi
      experimental, one group, pre- and post-test study design was used ( Box 1 ) with
      total sampling. Participants (n=17) were selected purposefully by including all
      ward managers (n=8) and assistant ward managers (n=9) from one university
      hospital department. The number of sudden absences among the nursing staff was
      identified during two 4-week data collection periods (pre- and post-test).
      Results During the use of the paper-based scheduling system, 121 absences were
      identified; during the use of the Excel-based system, 106 were identified. The
      main reasons for the use of flexible 'floating' nurses were sick leave (n=66) and
      workload (n=31). Other reasons (n=29) included patient transfer to another
      hospital, scheduling errors and the start or end of employment. Conclusion The
      Excel-based scheduling solution offered better support in obtaining substitute
      labour inside the organisation, with smaller employment costs. It also reduced
      the number of tasks ward managers had to carry out during the process of
      reallocating staff.

PMID- 27686917
TI  - Leadership in practice: an analysis of collaborative leadership in the conception
      of a virtual ward.
AB  - The National Health Service (NHS) in the UK is evolving to meet the needs of
      society, but success depends on effective leadership. The World Health
      Organization identified intersectoral and multidisciplinary working as key to
      improving the quality and sustainability of the service, highlighting the need
      for a new leadership style. This article describes how collaborative leadership
      was used to successfully implement a virtual ward in the primary care setting in
      south-east Powys, Wales. The author describes the leadership style and addresses
      strategies used to manage the change process. The journey demonstrates how
      collaborative leadership and working collectively enabled a new service to be
      developed, and established a mutual respect for different professionals' roles.

PMID- 27686918
TI  - Implementation of a structured programme of preceptorship for newly qualified
      midwives in a maternity unit.
AB  - This article discusses the application of a structured approach to the
      development and implementation of preceptorship programmes with an evidence-based
      content to support newly qualified midwives (NQMs). The development of a
      programme of preceptorship for NQMs is discussed and recommendations made for
      current practice. All NHS trusts should consider how preceptorship programmes can
      be developed and implemented with a clear, robust audit trail to identify how
      allocated funding is used.

PMID- 27686919
TI  - The art of the possible.
AB  - Why did you become a nurse? It was a little unexpected, I had the experience of a
      family member being in hospital and was inspired by the work of nurses and the
      difference they made.

PMID- 27686920
TI  - Transferring care from hospital to home.
AB  - The move towards healthcare being delivered predominantly in people's own homes
      has been seen as creating more choice and giving patients better access to care.
      How this is being delivered in practice is under question as district nursing
      teams endeavour to meet a range of needs and coordinate the transfer of care from
      hospital to home. The research project outlined in this article explored district
      nurses' views on what are the 'enablers' and 'barriers' to the transfer of care
      from hospital to home.

PMID- 27686922
TI  - Lactate measurement.
AB  - Serum lactate levels are frequently measured in patients with undifferentiated
      conditions in emergency departments. This article uses a case-based reflection to
      analyse the role of lactate measurement in these patients. It examines the
      rationale for testing and the potential causes of raised levels, to remind
      clinicians that this diagnostic intervention must be taken in the context of
      patients' clinical presentations and not in isolation.

PMID- 27686923
TI  - Online.
AB  - In the UK, there are an estimated 150,000 cases of sepsis per year, resulting in
      44,000 deaths. This equates to more deaths than from bowel, breast and prostate
      cancer combined according to the Sepsis Trust, 2016.

PMID- 27686921
TI  - Culture change in care homes.
AB  - This is the second of a two-part series exploring a programme of culture change
      in care homes.

PMID- 27686924
TI  - In other RCNi journals.
AB  - 'Given the potential benefits of tea for heart health, dental health and
      cognitive function, tea consumption could rise to eight servings daily and still
      remain within safe caffeine limits'.

PMID- 27686925
TI  - Time for MADIT-VAD?: ICDs Among LVAD Patients.

PMID- 27686926
TI  - The International Olympic Games: Heart Teams and Heart Failure.

PMID- 27686927
TI  - Reply: Size Matters? Seeking High-Risk Populations Among "Normal" Individuals.

PMID- 27686928
TI  - Size Matters?: Seeking High-Risk Populations Among "Normal" Individuals.

PMID- 27686929
TI  - EMS, HEMS, ECMO Center, ICU Team: Are You Ready for Hypothermic Patients?:
      Extracorporeal Membrane Oxygenation in Severe Accidental Hypothermia.

PMID- 27686930
TI  - Reply: EMS, HEMS, ECMO Center, ICU Team: Are You Ready for Hypothermic Patients?
      Extracorporeal Membrane Oxygenation in Severe Accidental Hypothermia.

PMID- 27686932
TI  - ?

PMID- 27686931
TI  - Redesigning Ventricular Assist Devices to Protect Ethnic Minorities: Changing
      Design With Changing Times.

PMID- 27686933
TI  - [Sarcopenia and frailty 2016 : Going separate ways].

PMID- 27686935
TI  - Orolingual angioedema after thrombolytic treatment.

PMID- 27686934
TI  - Early Prediction of Persistent Organ Failure by Serum Angiopoietin-2 in Patients
      with Acute Pancreatitis.
AB  - BACKGROUND: Biomarkers for the early prediction of the severity of acute
      pancreatitis (AP) are urgently needed for clinical management of the disease.
      Angiopoietin-2 (Ang-2), one of the autocrine peptides that reduce endothelial
      permeability, has been found to be associated with various diseases, including
      inflammatory disorders. AIMS: This study aimed to determine whether serum Ang-2
      could serve as a noninvasive biomarker for the early prediction of persistent
      organ failure (POF) in acute pancreatitis. METHODS: A total of 120 AP patients
      were prospectively enrolled at Jinling Hospital. Serum samples were collected on
      admission. Clinical and laboratory data were recorded. Ang-2 levels were measured
      by enzyme-linked immunosorbent assay. RESULTS: A total of 37 patients developed
      POF and were classified as having severe AP (SAP). Ang-2 was significantly higher
      on admission in patients who developed POF than in those who did not (p < 0.001
      for all). Furthermore, receiver operating characteristic (ROC) curve analysis
      revealed that Ang-2 could distinguish patients who developed POF from mild AP
      (MAP, area under ROC curve [AUC] = 0.88, 95 % CI 0.78-0.94) and moderately severe
      AP patients (MSAP, AUC = 0.74, 95 % CI 0.63-0.83). In addition, multivariate
      logistic regression showed that increased Ang-2 was an independent predictor of
      developing POF between subgroups with MSAP and SAP (OR 7.2, 95 % CI 2.7-19.4) and
      among all AP patients (OR 12.1, 95 % CI 4.8-30.3). CONCLUSIONS: Elevated serum
      Ang-2 levels on admission may be a promising biomarker for the prediction of POF
      in AP.

PMID- 27686936
TI  - Skin infection by Mycobacterium marinum.

PMID- 27686938
TI  - Evidence-Based Medicine: A Few Introductory Remarks.

PMID- 27686937
TI  - Saccular varix of pulmonary vein mimicking a pulmonary nodule.

PMID- 27686940
TI  - A survey for gregarines (Protozoa: Apicomplexa) in arthropods in Spain.
AB  - Gregarines thrive in the digestive tract of arthropods and may be deleterious to
      their hosts, especially when present in high densities. The impact of parasites
      on these invertebrates may affect both the ecosystem equilibrium and human
      economic activities. However, information available on gregarines in Spain is
      limited. Therefore, a microscopic study on prevalence of gregarine infection in
      560 insects and crustaceans was undertaken in Madrid and Tarragona.Gregarina
      ormierei (78 % prevalence), Stylocephalus gigas (56 %), Oocephalus hispanus (13
      %) and Actinocephalus permagnus (only one infected out of six beetles examined)
      were found in coleopteran hosts. Gregarina ovata and G. chelidurellae showed
      moderate frequency of infection (35 %) in dermapterans. An undescribed Gregarina
      sp. (76 % prevalence) was observed for the first time in freshwater decapod
      crustaceans. Interestingly, G. ormierei showed a noticeable phenotypic
      dimorphism, which justifies its redescription based on modern taxonomic criteria.
      Sequences of the 18S rRNA gene could be obtained only in the presence of highly
      prevalent gregarines. G. ormierei and Gregarina sp. were related (85 and 94 %
      identity by BLASTN, respectively) to G. basiconstrictonea and G. cloptoni,
      respectively, whereas S. gigas was closely related to both Xiphocephalus ellisi
      and S. giganteus (>97 % identity). Phylogenetic trees based on ribosomal
      sequences unequivocally grouped these new isolates either with the Gregarinidae
      (G. ormierei and Gregarina sp.) or the Stylocephalidae (S. gigas).

PMID- 27686941
TI  - Carboxymethyl Starch Excipients for Drug Chronodelivery.
AB  - Carboxymethyl starch (CMS) is a pH-responsive excipient exhibiting also
      interesting properties for applications in delayed drug delivery systems. This
      work was aimed to investigate the release properties of monolithic and dry-coated
      tablets based on ionic sodium CMS and on protonated CMS, formulated with three
      model tracers: acetaminophen, acetylsalicylic acid (ASA), and sodium diclofenac.
      The sodium or protonated CMS were obtained from the same CMS synthesis by
      controlling the final pH of reaction media. The two forms of CMS were confirmed
      by the Fourier transform infrared spectroscopy. The in vitro dissolution profiles
      for monolithic and double core tablets were different and allowed a better
      understanding of characteristics of the two excipient forms. It was found that
      the protonated CMS exhibited a better stability in simulated gastric fluid in
      comparison to its sodium salt in monolithic dosage forms, whereas both excipients
      afforded a complete gastric protection of drugs when formulated as dry-coated
      dosages. Determination of water uptake and erosion rate of monolithic matrices
      based on the two CMS forms showed different mechanisms involved in the delivery
      of the three model active molecules in simulated intestinal media. When
      pancreatic enzymes were added in dissolution media, the drug release was
      accelerated showing that CMS is still a substrate for alpha-amylase. Both sodium
      and protonated starch excipients, formulated as dry-coated dosages, afforded a
      good gastro-protection and allowed a drug chronodelivery at various intervals up
      to 4-5 h. They could be considered as an alternative for delayed delivery and a
      solvent-free coating procedure.

PMID- 27686942
TI  - Age differences in the takeover of vehicle control and engagement in non-driving
      related activities in simulated driving with conditional automation.
AB  - High-level vehicle automation has been proposed as a valuable means to enhance
      the mobility of older drivers, as older drivers experience age-related declines
      in many cognitive functions that are vital for safe driving. Recent research
      attempted to examine age differences in how engagement in non-driving-related
      activities impact driving performance, by instructing drivers to engage in
      mandatory pre-designed activities. While the mandatory engagement method allows a
      precise control of the timing and mental workload of the non-driving-related
      activities, it is different from how a driver would naturally engage in these
      activities. This study allowed younger (age 18-35, mean age=19.9years) and older
      drivers (age 62-81, mean age=70.4years) to freely decide when and how to engage
      in voluntarily chosen non-driving-related activities during simulated driving
      with conditional automation. We coded video recordings of participants'
      engagement in non-driving-related activities. We examined the effect of age,
      level of activity-engagement and takeover notification interval on vehicle
      control performance during the takeover, by comparing between the high and low
      engagement groups in younger and older drivers, across two takeover notification
      interval conditions. We found that both younger and older drivers engaged in
      various non-driving-related activities during the automated driving portion, with
      distinct preferences on the type of activity for each age group (i.e., while
      younger drivers mostly used an electronic device, older drivers tended to
      converse). There were also significant differences between the two age groups and
      between the two notification intervals on various driving performance measures.
      Older drivers benefited more than younger drivers from the longer interval in
      terms of response time to notifications. Voluntary engagement in non-driving
      related activities did not impair takeover performance in general, although there
      was a trend of older drivers who were more engaged in non-driving-related
      activities braking harder than those with low activity-engagement during the
      takeover.

PMID- 27686943
TI  - Health-related quality of life in patients with high-risk low-grade glioma (EORTC
      22033-26033): a randomised, open-label, phase 3 intergroup study.
AB  - BACKGROUND: Temozolomide chemotherapy versus radiotherapy in patients with a high
      risk low-grade glioma has been shown to have no significant effect on progression
      free survival. If these treatments have a different effect on health-related
      quality of life (HRQOL), it might affect the choice of therapy. We postulated
      that temozolomide compromises HRQOL and global cognitive functioning to a lesser
      extent than does radiotherapy. METHODS: We did a prospective, phase 3, randomised
      controlled trial at 78 medical centres and large hospitals in 19 countries. We
      enrolled adult patients (aged >=18 years) with histologically confirmed diffuse
      (WHO grade II) astrocytoma, oligodendroglioma, or mixed oligoastrocytoma, with a
      WHO performance status of 2 or lower, without previous chemotherapy or
      radiotherapy, who needed active treatment other than surgery. We randomly
      assigned eligible patients (1:1) using a minimisation technique, stratified by
      WHO performance status (0-1 vs 2), age (<40 years vs >=40 years), presence of
      contrast enhancement on MRI, chromosome 1p status (deleted vs non-deleted vs
      indeterminate), and the treating medical centre, to receive either radiotherapy
      (50.4 Gy in 28 fractions of 1.8 Gy for 5 days per week up to 6.5 weeks) or
      temozolomide chemotherapy (75 mg/m2 daily, for 21 of 28 days [one cycle] for 12
      cycles). The primary endpoint was progression-free survival (results published
      separately); here, we report the results for two key secondary endpoints: HRQOL
      (assessed using the European Organisation for Research and Treatment of Cancer's
      [EORTC] QLQ-C30 [version 3] and the EORTC Brain Cancer Module [QLQ-BN20]) and
      global cognitive functioning (assessed using the Mini-Mental State Examination
      [MMSE]). We did analyses on the intention-to-treat population. This study is
      closed and is registered at EudraCT, number 2004-002714-11, and at
      ClinicalTrials.gov, number NCT00182819. FINDINGS: Between Dec 6, 2005, and Dec
      21, 2012, we randomly assigned 477 eligible patients to either radiotherapy
      (n=240) or temozolomide chemotherapy (n=237). The difference in HRQOL between the
      two treatment groups was not significant during the 36 months' follow-up (mean
      between group difference [averaged over all timepoints] 0.06, 95% CI -4.64 to
      4.75, p=0.98). At baseline, 32 (13%) of 239 patients who received radiotherapy
      and 32 (14%) of 236 patients who received temozolomide chemotherapy had impaired
      cognitive function, according to the MMSE scores. After randomisation, five (8%)
      of 63 patients who received radiotherapy and three (6%) of 54 patients who
      received temozolomide chemotherapy and who could be followed up for 36 months had
      impaired cognitive function, according to the MMSE scores. No significant
      difference was recorded between the groups for the change in MMSE scores during
      the 36 months of follow-up. INTERPRETATION: The effect of temozolomide
      chemotherapy or radiotherapy on HRQOL or global cognitive functioning did not
      differ in patients with low-grade glioma. These results do not support the choice
      of temozolomide alone over radiotherapy alone in patients with high-risk low
      grade glioma. FUNDING: Merck Sharp & Dohme-Merck & Co, National Cancer Institute,
      Swiss Cancer League, National Institute for Health Research, Cancer Research UK,
      Canadian Cancer Society Research Institute, National Health and Medical Research
      Council, European Organisation for Research and Treatment of Cancer Cancer
      Research Fund.

PMID- 27686944
TI  - Return of induction chemotherapy in head and neck squamous cell cancers: is this
      time different?

PMID- 27686945
TI  - Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent
      chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a
      phase 3, multicentre, randomised controlled trial.
AB  - BACKGROUND: The value of adding cisplatin, fluorouracil, and docetaxel (TPF)
      induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced
      nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction
      chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy
      alone in a suitably powered trial. METHODS: We did an open-label, phase 3,
      multicentre, randomised controlled trial at ten institutions in China. Patients
      with previously untreated, stage III-IVB (except T3-4N0) nasopharyngeal
      carcinoma, aged 18-59 years without severe comorbidities were enrolled. Eligible
      patients were randomly assigned (1:1) to receive induction chemotherapy plus
      concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles
      of 100 mg/m2 cisplatin every 3 weeks, concurrently with intensity-modulated
      radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel
      (60 mg/m2 on day 1), intravenous cisplatin (60 mg/m2 on day 1), and continuous
      intravenous fluorouracil (600 mg/m2 per day from day 1 to day 5) every 3 weeks
      before concurrent chemoradiotherapy. Randomisation was by a computer-generated
      random number code with a block size of four, stratified by treatment centre and
      disease stage (III or IV). Treatment allocation was not masked. The primary
      endpoint was failure-free survival calculated from randomisation to locoregional
      failure, distant failure, or death from any cause; required sample size was 476
      patients (238 per group). We did efficacy analyses in our intention-to-treat
      population. The follow-up is ongoing; in this report, we present the 3-year
      survival results and acute toxic effects. This trial is registered with
      ClinicalTrials.gov, number NCT01245959. FINDINGS: Between March 1, 2011, and Aug
      22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent
      chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median
      follow-up of 45 months (IQR 38-49), 3-year failure-free survival was 80% (95% CI
      75-85) in the induction chemotherapy plus concurrent chemoradiotherapy group and
      72% (66-78) in the concurrent chemoradiotherapy alone group (hazard ratio 0.68,
      95% CI 0.48-0.97; p=0.034). The most common grade 3 or 4 adverse events during
      treatment in the 239 patients in the induction chemotherapy plus concurrent
      chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy
      alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41
      [17%]), and stomatitis (98 [41%] vs 84 [35%]). INTERPRETATION: Addition of TPF
      induction chemotherapy to concurrent chemoradiotherapy significantly improved
      failure-free survival in locoregionally advanced nasopharyngeal carcinoma with
      acceptable toxicity. Long-term follow-up is required to determine long-term
      efficacy and toxicities. FUNDING: Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat
      sen University Clinical Research 5010 Program (2007037), National Science and
      Technology Pillar Program during the Twelfth Five-year Plan Period
      (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou
      City (201400000001), Planned Science and Technology Project of Guangdong Province
      (2013B020400004), and The National Key Research and Development Program of China
      (2016YFC0902000).

PMID- 27686947
TI  - Does an optimum treatment for high-risk low-grade gliomas exist?

PMID- 27686946
TI  - Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma
      (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study.
AB  - BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable,
      reflecting molecular heterogeneity of the disease. We compared two different,
      single-modality treatment strategies of standard radiotherapy versus primary
      temozolomide chemotherapy in patients with low-grade glioma, and assessed
      progression-free survival outcomes and identified predictive molecular factors.
      METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033
      26033), undertaken in 78 clinical centres in 19 countries, we included patients
      aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma,
      oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged
      >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline,
      or neurological symptoms), and without known HIV infection, chronic hepatitis B
      or C virus infection, or any condition that could interfere with oral drug
      administration. Eligible patients were randomly assigned (1:1) to receive either
      conformal radiotherapy (up to 50.4 Gy; 28 doses of 1.8 Gy once daily, 5 days per
      week for up to 6.5 weeks) or dose-dense oral temozolomide (75 mg/m2 once daily
      for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).
      Random treatment allocation was done online by a minimisation technique with
      prospective stratification by institution, 1p deletion (absent vs present vs
      undetermined), contrast enhancement (yes vs no), age (<40 vs >=40 years), and WHO
      performance status (0 vs >=1). Patients, treating physicians, and researchers
      were aware of the assigned intervention. A planned analysis was done after 216
      progression events occurred. Our primary clinical endpoint was progression-free
      survival, analysed by intention-to-treat; secondary outcomes were overall
      survival, adverse events, neurocognitive function (will be reported separately),
      health-related quality of life and neurological function (reported separately),
      and correlative analyses of progression-free survival by molecular markers
      (1p/19q co-deletion, MGMT promoter methylation status, and IDH1/IDH2 mutations).
      This trial is closed to accrual but continuing for follow-up, and is registered
      at the European Trials Registry, EudraCT 2004-002714-11, and at
      ClinicalTrials.gov, NCT00182819. FINDINGS: Between Sept 23, 2005, and March 26,
      2010, 707 patients were registered for the study. Between Dec 6, 2005, and Dec
      21, 2012, we randomly assigned 477 patients to receive either radiotherapy
      (n=240) or temozolomide chemotherapy (n=237). At a median follow-up of 48 months
      (IQR 31-56), median progression-free survival was 39 months (95% CI 35-44) in the
      temozolomide group and 46 months (40-56) in the radiotherapy group (unadjusted
      hazard ratio [HR] 1.16, 95% CI 0.9-1.5, p=0.22). Median overall survival has not
      been reached. Exploratory analyses in 318 molecularly-defined patients confirmed
      the significantly different prognosis for progression-free survival in the three
      recently defined molecular low-grade glioma subgroups (IDHmt, with or without
      1p/19q co-deletion [IDHmt/codel], or IDH wild type [IDHwt]; p=0.013). Patients
      with IDHmt/non-codel tumours treated with radiotherapy had a longer progression
      free survival than those treated with temozolomide (HR 1.86 [95% CI 1.21-2.87],
      log-rank p=0.0043), whereas there were no significant treatment-dependent
      differences in progression-free survival for patients with IDHmt/codel and IDHwt
      tumours. Grade 3-4 haematological adverse events occurred in 32 (14%) of 236
      patients treated with temozolomide and in one (<1%) of 228 patients treated with
      radiotherapy, and grade 3-4 infections occurred in eight (3%) of 236 patients
      treated with temozolomide and in two (1%) of 228 patients treated with
      radiotherapy. Moderate to severe fatigue was recorded in eight (3%) patients in
      the radiotherapy group (grade 2) and 16 (7%) in the temozolomide group. 119 (25%)
      of all 477 patients had died at database lock. Four patients died due to
      treatment-related causes: two in the temozolomide group and two in the
      radiotherapy group. INTERPRETATION: Overall, there was no significant difference
      in progression-free survival in patients with low-grade glioma when treated with
      either radiotherapy alone or temozolomide chemotherapy alone. Further data
      maturation is needed for overall survival analyses and evaluation of the full
      predictive effects of different molecular subtypes for future individualised
      treatment choices. FUNDING: Merck Sharpe & Dohme-Merck & Co, Canadian Cancer
      Society, Swiss Cancer League, UK National Institutes of Health, Australian
      National Health and Medical Research Council, US National Cancer Institute,
      European Organisation for Research and Treatment of Cancer Cancer Research Fund.

PMID- 27686949
TI  - Alkali-activated concrete with Serbian fly ash and its radiological impact.
AB  - The present paper reports the results of a study on different types of fly ash
      from Serbian coal burning power plants and their potential use as a binder in
      alkali-activated concrete (AAC) depending on their radiological and mechanical
      properties. Five AAC mixtures with different types of coal burning fly ash and
      one type of blast furnace slag were designed. Measurements of the activity
      concentrations of 40K, 226Ra and 232Th were done both on concrete constituents
      (fly ash, blast furnace slag and aggregate) and on the five solid AAC samples.
      Experimental results were compared by using the activity concentration assessment
      tool for building materials - the activity concentration index I, as introduced
      by the EU Basic Safety Standards (CE, 2014). All five designed alkali-activated
      concretes comply with EU BSS screening requirements for indoor building
      materials. Finally, index I values were compared with the results of the
      application of a more accurate index - I(rhod), which accounts for thickness and
      density of building materials (Nuccetelli et al., 2015a). Considering the actual
      density and thickness of each concrete sample index - I(rhod) values are lower
      than index I values. As an appendix, a synthesis of main results concerning
      mechanical and chemical properties is provided.

PMID- 27686948
TI  - Levodopa medication improves incidental sequence learning in Parkinson's disease.
AB  - Empirical evidence suggests that levodopa medication used to treat the motor
      symptoms of Parkinson's disease (PD) may either improve, impair or not affect
      specific cognitive processes. This evidence led to the 'dopamine overdose'
      hypothesis that levodopa medication impairs performance on cognitive tasks if
      they recruit fronto-striatal circuits which are not yet dopamine-depleted in
      early PD and as a result the medication leads to an excess of dopamine. This
      hypothesis has been supported for various learning tasks including conditional
      associative learning, reversal learning, classification learning and intentional
      deterministic sequence learning, on all of which PD patients demonstrated
      significantly worse performance when tested on relative to off dopamine
      medication. Incidental sequence learning is impaired in PD, but how such learning
      is affected by dopaminergic therapy remains undetermined. The aim of the current
      study was to investigate the effect of dopaminergic medication on incidental
      sequence learning in PD. We used a probabilistic serial reaction time task
      (SRTT), a sequence learning paradigm considered to make the sequence less
      apparent and more likely to be learned incidentally rather than intentionally. We
      compared learning by the same group of PD patients (n=15) on two separate
      occasions following oral administration of levodopa medication (on state) and
      after overnight withdrawal of medication (off state). Our results demonstrate for
      the first time that levodopa medication enhances incidental learning of a
      probabilistic sequence on the serial reaction time task in PD. However, neither
      group significantly differed from performance of a control group without a
      neurological disease, which indicates the importance of within group comparisons
      for identifying deficits. Levodopa medication enhanced incidental learning by
      patients with PD on a probabilistic sequence learning paradigm even though the
      patients were not aware of the existence of the sequence or their acquired
      knowledge. The results suggest a role in acquiring incidental motor sequence
      learning for dorsal striatal areas strongly affected by dopamine depletion in
      early PD.

PMID- 27686951
TI  - Cohort Profile: Ten to Men (the Australian Longitudinal Study on Male Health).

PMID- 27686950
TI  - Gout and Osteoarthritis: Associations, Pathophysiology, and Therapeutic
      Implications.
AB  - Osteoarthritis (OA), the most common type of arthritis worldwide, is a
      degenerative disease of diarthrodial joints resulting in pain, reduced quality of
      life, and socioeconomic burden. Gout, the most common form of inflammatory
      arthritis, is a consequence of persistently elevated levels of urate and the
      formation of proinflammatory monosodium urate crystals in joints. Clinicians have
      long noted a predilection for both diseases to occur in the same joints. In this
      review, we provide an overview into research elucidating possible biochemical,
      mechanical, and immunological relationships between gout and OA. We additionally
      consider the potential implications of these relationships for OA treatment.

PMID- 27686953
TI  - Congo fever rears its head again in Pakistan.

PMID- 27686952
TI  - Predicting violence and recidivism in a large sample of males on probation or
      parole.
AB  - This study evaluated the utility of items and scales from the Iowa Violence and
      Victimization Instrument in a sample of 1961 males from the state of Iowa who
      were on probation or released from prison to parole supervision. This is the
      first study to examine the potential of the Iowa Violence and Victimization
      Instrument to predict criminal offenses. The males were followed for 30months
      immediately following their admission to probation or parole. AUC analyses
      indicated fair to good predictive power for the Iowa Violence and Victimization
      Instrument for charges of violence and victimization, but chance predictive power
      for drug offenses. Notably, both scales of the instrument performed equally well
      at the 30-month follow-up. Items on the Iowa Violence and Victimization
      Instrument not only predicted violence, but are straightforward to score.
      Violence management strategies are discussed as they relate to the current
      findings, including the potential to expand the measure to other jurisdictions
      and populations.

PMID- 27686955
TI  - Ondansetron in pregnancy and risk of adverse fetal outcomes in the United States.

PMID- 27686954
TI  - In vitro exposure of human spermatozoa to bisphenol A induces pro
      oxidative/apoptotic mitochondrial dysfunction.
AB  - As bisphenol A (BPA) exerts oxidative/pro-apoptotic effects in several cell
      types, we explored whether the in vitro exposure to BPA could affect human sperm
      integrity through the induction of pro-oxidative/apoptotic mitochondrial
      dysfunction. The exposure of motile sperm suspensions to scalar BPA
      concentrations for 4h produced a decrease in the mitochondrial membrane
      potential, starting from 300MUM. It was associated with an increased
      mitochondrial generation of superoxide anion, caspase-9 and caspase-3 activation
      and motility decrement. Vitality decline was observed at BPA>=400MUM. Twenty
      hours exposure to 300MUM BPA, but not to lower concentrations, produced a
      significant loss in sperm vitality associated with a complete sperm
      immobilization. Finally, 300MUM BPA also produced a significant DNA oxidative
      damage, as revealed by the formation of oxidized base adduct 8-hydroxy-2'
      deoxyguanosine. In conclusion, BPA affected human sperm integrity by inducing pro
      oxidative/apoptotic mitochondrial dysfunction.

PMID- 27686956
TI  - Parents' emotional status, ADHD symptoms and sleep problems in children with
      epilepsy.

PMID- 27686958
TI  - Trehalose, an easy, safe and efficient cryoprotectant for the parasitic protozoan
      Trypanosoma brucei.
AB  - Trehalose, a non-permeating cryoprotective agent (CPA), has been documented as
      less toxic and highly efficient at cryopreserving different kinds of cells or
      organisms. In the present study, trehalose was evaluated for its application in
      cryopreservation of both Trypanosoma brucei procyclic and bloodstream form cells.
      The cryopreservation efficiency was determined by the motility of trypanosomes
      after thawing, as well as a subsequent recovery and infectivity assessment. The
      viability of trypanosomes from cultivation that were frozen in a serial
      concentrations of trehalose showed similar results to classical CPAs of glycerol
      and DMSO. Nevertheless, trypanosomes cryopreserved in 0.2M trehalose showed the
      best growth characteristic during subsequent cultivation. In addition, CPA
      cocktails with trehalose and permeating CPA glycerol or DMSO were developed and
      evaluated. Interestingly, trypanosomes in host (mouse) blood cryopreserved in
      0.4M trehalose plus 5% glycerol showed higher infectivity than those preserved in
      trehalose/DMSO cocktails as well as individually. Further investigations showed
      that, in comparison with slow freezing at -80 degrees C, flash freezing in liquid
      nitrogen provided better cryopreservation for bloodstream form cells than slow
      freezing. In conclusion, trehalose is an easy, safe and efficient CPA for
      cryopreservation of T. brucei and potentially for other protozoan species and
      cells.

PMID- 27686959
TI  - First detection and molecular identification of Babesia gibsoni from
      Rhipicephalus sanguineus ticks.
AB  - Babesia gibsoni was firstly identified in Rhipicephalus sanguineus ticks infested
      on dogs in Asia. A total of 1195 ticks collected from veterinary practitioners
      and pet clinics were examined for Babesia by nested-polymerase chain reaction
      assay based on the 18S small subunit ribosomal RNA (ssrRNA) gene. Babesia
      infection was detected in nymph, male and female ticks with an infection rate of
      2.42%, 0.98% and 1.97%, respectively. Sequence and phylogenetic analysis revealed
      that these Babesia spp. were genetically affiliated to the same clades within the
      genospecies of B. gibsoni and B. vogeli, and can be discriminated from other
      genospecies of Babesia. Intra- and inter-species analysis based on the genetic
      distance (GD) values indicated a lower level in B. gibsoni (GD<0.011) compared
      with other genospecies of Babesia (GD>0.106) and out-group protozoa (GD>0.244).
      This study provides the first molecular evidence of B. gibsoni identified in
      nymphs of R. sanguineus ticks in Asia, and further confirms the detection of B.
      vogeli in nymphs and adults of R. sanguineus in northern Taiwan. The
      epizootiological significance of canine Babesia spp. transmitted by R. sanguineus
      tick needs to be further identified.

PMID- 27686957
TI  - The effect of Lucilia sericata- and Sarconesiopsis magellanica-derived larval
      therapy on Leishmania panamensis.
AB  - This study's main objective was to evaluate the action of larval therapy derived
      from Lucilia sericata and Sarconesiopsis magellanica (blowflies) regarding
      Leishmania panamensis using an in vivo model. Eighteen golden hamsters
      (Mesocricetus auratus) were used; they were divided into 6 groups. The first
      three groups consisted of 4 animals each; these, in turn, were internally
      distributed into subgroups consisting of 2 hamsters to be used separately in
      treatments derived from each blowfly species. Group 1 was used in treating
      leishmanial lesions with larval therapy (LT), whilst the other two groups were
      used for evaluating the used of larval excretions and secretions (ES) after the
      ulcers had formed (group 2) and before they appeared (group 3). The three
      remaining groups (4, 5 and 6), consisting of two animals, were used as controls
      in the experiments. Biopsies were taken for histopathological and molecular
      analysis before, during and after the treatments; biopsies and smears were taken
      for assessing parasite presence and bacterial co-infection. LT and larval ES
      proved effective in treating the ulcers caused by the parasite. There were no
      statistically significant differences between the blowfly species regarding the
      ulcer cicatrisation parameters. There were granulomas in samples taken from
      lesions at the end of the treatments. The antibacterial action of larval
      treatment regarding co-infection in lesions caused by the parasite was also
      verified. These results potentially validate effective LT treatment against
      cutaneous leishmaniasis aimed at using it with humans in the future.

PMID- 27686960
TI  - Kerteszia Theobald (Diptera: Culicidae) mosquitoes and bromeliads: A landscape
      ecology approach regarding two species in the Atlantic rainforest.
AB  - On the ecological scale of an organism, a homogeneous geographical landscape can
      represent a mosaic of heterogeneous landscapes. The bionomy of Kerteszia
      mosquitoes can contribute to foundation landscape ecology by virtue of in the
      role of the configuration and composition of the habitat played in the
      distribution of mosquito species. Thus, this study aimed: to compare the
      abundance of Kerteszia in dense tropical rainforest, restinga and rural area, to
      assess the bioecological characteristics of the main bromeliads hosting
      Kerteszia, and to associate the bioecological arrangement of the bromeliads with
      Kerteszia distribution. Field collections were conducted in a monthly schedule
      from December of 2010 to November 2011. The vegetation of landscapes was
      characterized on the basis of a digital cartographic database, the manual of the
      Brazilian vegetation, environmental atlas information, satellite images and
      visits to the sites. Multivariate generalized linear models were employed using
      the R-project statistical program. The results were: Anopheles cruzii was the
      most frequent species in dense tropical rainforest (67.42%), with a positive
      association (deviance=25.8; P=0.002). Anopheles bellator was more abundant in the
      Restinga area (78.97%), with a positive association (deviance=10.4, P=0.018).
      There was a positive aggregation of Restinga with An. bellator (RR=2.42) but a
      lower level with An. cruzii (RR=0.31). Thus we can conclude that landscape
      characteristics influence the distribution of Kerteszia mosquitoes. An. bellator
      has a higher prevalence in Restinga areas, whereas An. cruzii was the most
      prevalent in the dense tropical rainforest.

PMID- 27686962
TI  - Efficacy and safety of pharmacological treatments for Lyme neuroborreliosis in
      children: a systematic review.
AB  - BACKGROUND: Many aspects of pharmacological treatment of Lyme neuroborreliosis in
      children, such as choice of drug, dosage, and duration are subject to intense
      debates, leading to uncertainties in patients' parents and healthcare providers
      alike. To assess the available evidence for pharmacological treatment for
      children with Lyme neuroborreliosis we conducted a systematic review. METHODS:
      The comprehensive systematic literature search included randomized-controlled
      trials (RCTs) and non-randomized studies (NRS) on treatment of Lyme
      neuroborreliosis in children (age <18 years). Our primary outcome was
      neurological symptoms after treatment. Risk of bias was assessed with the
      Cochrane risk of bias tools for RCTs and NRS. Quality of evidence was assessed
      using the Grading of Recommendations Assessment, Development and Evaluation
      (GRADE) approach. RESULTS: Two RCTs and four NRS were eligible for inclusion.
      Risk of bias in RCTs and NRS was generally high. Reporting of studies was
      generally poor. Regarding the primary outcome neurological symptoms at 1-3
      months, no statistically significant difference could be found in cohort studies
      between doxycycline and beta-lactam antibiotics. In two RCTs comparing penicillin
      G and ceftriaxone, no patient experienced residual neurological symptoms at the
      last reported time points. Quality of evidence according to GRADE was judged very
      low. CONCLUSIONS: Data is scarce and with limited quality. Several issues could
      not be addressed due to scarcity of information. No eligible study compared
      different treatment durations. According to the available evidence, there seems
      to be no difference between different antibiotic agents for the treatment of Lyme
      neuroborreliosis in children regarding neurological symptoms. We found no
      evidence that supports extended antibiotic regimes. REVIEW REGISTRATION:
      Systematic review registration: CRD42014008839 .

PMID- 27686961
TI  - Role of placental barrier integrity in infection by Trypanosoma cruzi.
AB  - American trypanosomiasis has long been a neglected disease endemic in
      LatinAmerica, but congenital transmission has now spread Chagas disease to cause
      a global health problem. As the early stages of the infection of placental tissue
      and the vertical transmission by Trypanosoma cruzi are still not well understood,
      it is important to investigate the relevance of the first structure of the
      placental barrier in chorionic villi infection by T. cruzi during the initial
      stage of the infection. Explants of human chorionic villi from healthy pregnant
      women at term were denuded of their syncytiotrophoblast and co-cultured for 3h,
      24h and 96h with 800,000 trypomastigotes (simulating acute infection). T. cruzi
      infected cells were identified by immunohistochemistry for cytokeratin-7
      (+cytotrophoblast) and CD68 (+macrophages), and the infection was quantified. In
      placental tissue, the parasite load was analyzed by qPCR and microscopy, and the
      motile trypomastigotes were quantified in culture supernatant. In denuded
      chorionic villous, the total area occupied by the parasite (451.23MUm2, 1.33%)
      and parasite load (RQ: 87) was significantly higher (p<0.05) than in the entire
      villous (control) (5.98MUm2, 0.016%) (RQ:1) and with smaller concentration of
      nitric oxide. Stromal non-macrophage cells were infected as well as
      cytotrophoblasts and some macrophages, but with significant differences being
      observed. The parasite quantity in the culture supernatant was significantly
      higher (p<0.05) in denuded culture explants from 96h of culture. Although the
      human complete chorionic villi limited the infection, the detachment of the first
      structure of the placenta barrier (syncytiotrophoblast) increased both the
      infection of the villous stroma and the living trypomastigotes in the culture
      supernatant. Therefore structural and functional alterations to chorionic villi
      placental barrier reduce placental defenses and may contribute to the vertical
      transmission of Chagas.

PMID- 27686963
TI  - Safety profile of biologic drugs in the therapy of Crohn disease: A systematic
      review and network meta-analysis.
AB  - BACKGROUND: Crohn disease (CD) is an inflammatory bowel disease which occurs
      especially in developed countries of Western Europe and North America. The aim of
      the study was to compare the safety profile of biologic drugs in patients with
      CD. METHODOLOGY: A systematic literature search was performed using PubMed,
      Embase, and CENTRAL databases, until April 27, 2016. We included randomized
      controlled trials (RCTs) that compared the safety of biologic drugs (infliximab,
      adalimumab, vedolizumab, certolizumab pegol, and ustekinumab) with one another or
      with placebo in patients with CD. The network meta-analysis (NMA) was conducted
      for an induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a
      Bayesian hierarchical random effects model in the ADDIS(r) software. The PROSPERO
      registration number was CRD42016032606. RESULTS: Ten RCTs were included in the
      systematic review with NMA. In the case of the induction phase, the NMA could be
      conducted for the assessment of the relative safety profile of adalimumab,
      vedolizumab, certolizumab pegol, and ustekinumab, and in the case of the
      maintenance phase-of infliximab, adalimumab, and vedolizumab. There were no
      significant differences in the rate of adverse events in patients treated with
      biologics. Statistical analysis revealed that vedolizumab had the greatest
      probability of being the safest treatment in most endpoints in the induction
      phase and adalimumab-in the maintenance phase. CONCLUSIONS: No significant
      differences between the biologics in the relative safety profile analysis were
      observed. Further studies are needed to confirm our findings, including head-to
      head comparisons between the analyzed biologics.

PMID- 27686964
TI  - The antifibrotic effects of alveolar macrophages 5-HT2C receptors blockade on
      bleomycin-induced pulmonary fibrosis in rats.
AB  - BACKGROUND: The most widespread chronic fibrosing lung disease is idiopathic
      pulmonary fibrosis. Lung serotonin (5-HT) content is increased during pulmonary
      fibrosis with the implication of 5-HT2 receptors in the pathogenesis. Serotonin
      plays important roles in alveolar macrophages function through 5-HT2C receptors
      activation. Numerous studies described the important role of 5-HT2A/B receptor
      blockers in suppressing different types of fibrosis as idiopathic pulmonary
      fibrosis. The current study pointed to examine the antifibrotic effects of RS
      102221 and/or terguride through in vivo model of pulmonary fibrosis. METHODS:
      Induction of pulmonary fibrosis was through a single dose of intra-tracheal
      bleomycin instillation (5mg/kg dissolved in phosphate buffer saline) in adult
      male albino Wistar rats. Next day of bleomycin instillation, intraperitoneal
      injection of RS-102221 (0.5mg/kg/d) and/or terguride (1.2mg/kg/d) were
      administered and continued for 14 days. RESULTS: Noticeable increase in 5-HT2C
      receptors expression was observed in fibrotic lung tissues with marked allocation
      belonging to alveolar macrophages. Either RS-102221 or terguride reduced the
      increments in lung water contents, grading of lung fibrosis, lung tumor necrosis
      factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) and
      vascular endothelial growth factor (VEGF) levels in lung injury and fibrosis
      induced by bleomycin. Moreover, collagen content and myofibroblasts-alpha smooth
      muscle actin (alpha-SMA) were significantly decreased. Additionally, the
      simultaneous administration of RS-102221 with terguride had a synergistic outcome
      compared to that obtained by individual monotherapy. CONCLUSION: These findings
      suggested the potential use of 5-HT2A/B/C antagonists as anti-fibrotic agents in
      lung fibrosis.

PMID- 27686965
TI  - Benzimidazole-core as an antimycobacterial agent.
AB  - Mycobacterium tuberculosis (Mtb) is considered as one of the precarious bacterial
      infections around the world. Through a projected 8.7 million new tuberculosis
      (TB) cases and 1.4 million mortalities per annum, this deadly infection resulted
      insubstantial amount of human deaths than any other single organism bacterial
      infections. TB is one of India's most threatening human health problems and it
      accounts for approximately 33% of the global health issues. Subsequently, for TB
      there is an imperative need for the improvement of existing drug candidates with
      newer targets and specified mechanism of action. Within the wide spectra of
      heterocycles, benzimidazole and its substituted analogues were evidenced
      promising biological efficacies enabling them to perform as new drug or prodrug
      candidates. Exceptional structural features of this class of heterocycle and
      versatile biological applications made it a privileged structural backbone in new
      drug design and discovery. Majorly, 2,5- and 2,6-disubstituted benzimidazole
      derivatives shown to induce significant antiTB potential. To seek more insights
      on this unique feature of benzimidazole candidates, there is an urgency to
      assemble the recent advances in this promising area. This review presents an
      overview of the recent advancements and focuses on the structural features
      responsible for unique antiTB applications and compiled published reports on
      benzimidazole derivatives emphasizing on different approaches employed for their
      syntheses in order to help medicinal and clinical chemists in designing next
      generation, yet effective and safer antiTB candidates.

PMID- 27686966
TI  - Combretastatins: In vitro structure-activity relationship, mode of action and
      current clinical status.
AB  - For the first time combretastatins were isolated from African willow tree
      Combretum Caffrum. Subsequent studies have shown the impact of combretastatin A4
      phosphate, a water-soluble prodrug, on endothelial cells in tumor vascular
      system. The same effect was not observed in the vascular system. This selectivity
      is associated with combretastatins mechanism of action: binding to colchicine
      domain of microtubules, which affects the cytoskeleton functionality of immature
      endothelial cells. At the same time, combretastatins directly induce cell death
      via apoptosis and/or mitotic catastrophe pathways. The combination of both
      elements makes combretastatin an anticancer compound of high efficiency. The cis
      configuration is crucial for its biological activity. To date, many derivatives
      were synthesized. The attempts to resolve spontaneous isomerization to less
      active trans-stilbene derivative are still in progress. This issue seems to be
      overcome by incorporation of the ethene bridge with heterocyclic moiety in
      combretastatins structure. This modification retains the cis-configuration and
      prevents isomerization. Nevertheless, combretastatin A4 phosphate disodium is
      still the most potent compound of this group. The combination therapy, which is
      the most effective treatment, includes combretastatin A4 phosphate (CA4P) and
      conventional chemotherapeutics and/or radiotherapy. CA4P is relatively well
      tolerated giving adverse events of moderate severity, which includes: nausea,
      vomiting, headache, and tumor pain. The aforementioned effects subside on the day
      of drug administration or on the following day.

PMID- 27686968
TI  - Stereotactic Body Radiotherapy Virtual Special Issue.

PMID- 27686967
TI  - Rapamycin negatively impacts insulin signaling, glucose uptake and uncoupling
      protein-1 in brown adipocytes.
AB  - New onset diabetes after transplantation (NODAT) is a metabolic disorder that
      affects 40% of patients on immunosuppressive agent (IA) treatment, such as
      rapamycin (also known as sirolimus). IAs negatively modulate insulin action in
      peripheral tissues including skeletal muscle, liver and white fat. However, the
      effects of IAs on insulin sensitivity and thermogenesis in brown adipose tissue
      (BAT) have not been investigated. We have analyzed the impact of rapamycin on
      insulin signaling, thermogenic gene-expression and mitochondrial respiration in
      BAT. Treatment of brown adipocytes with rapamycin for 16h significantly decreased
      insulin receptor substrate 1 (IRS1) protein expression and insulin-mediated
      protein kinase B (Akt) phosphorylation. Consequently, both insulin-induced
      glucose transporter 4 (GLUT4) translocation to the plasma membrane and glucose
      uptake were decreased. Early activation of the N-terminal Janus activated kinase
      (JNK) was also observed, thereby increasing IRS1 Ser 307 phosphorylation. These
      effects of rapamycin on insulin signaling in brown adipocytes were partly
      prevented by a JNK inhibitor. In vivo treatment of rats with rapamycin for three
      weeks abolished insulin-mediated Akt phosphorylation in BAT. Rapamycin also
      inhibited norepinephrine (NE)-induced lipolysis, the expression of peroxisome
      proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) and
      uncoupling protein (UCP)-1 in brown adipocytes. Importantly, basal mitochondrial
      respiration, proton leak and maximal respiratory capacity were significantly
      decreased in brown adipocytes treated with rapamycin. In conclusion, we
      demonstrate, for the first time the important role of brown adipocytes as target
      cells of rapamycin, suggesting that insulin resistance in BAT might play a major
      role in NODAT development.

PMID- 27686969
TI  - First-line Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors for EGFR
      Mutant Non-small Cell Lung Cancer: And the Winner is....

PMID- 27686970
TI  - Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in
      Nonmetastatic Small Cell Lung Carcinoma.
AB  - BACKGROUND: The optimal timing of thoracic radiation therapy (RT) in relation to
      chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer
      (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on
      overall survival (OS) of RT timing with chemotherapy for patients with SCLC.
      MATERIALS AND METHODS: The NCDB was queried for patients diagnosed with
      nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation.
      The patients were stratified into quartiles according to the interval between the
      start of chemotherapy and the start of RT. The first and second quartiles (RT
      started 0-20 days after chemotherapy) were classified as "early" RT and the third
      and fourth quartiles (RT started 21-126 days after chemotherapy) as "late" RT.
      Patients were included if they had received hyperfractionated 45 Gy in 30
      fractions or standard fractionation of >= 60 Gy in 1.8- to 2-Gy fractions. Kaplan
      Meier analyses of OS were performed, and multivariable Cox regression analysis
      was conducted to assess the effect of the covariates on OS. RESULTS: A total of
      8391 patients were included (50.5% had received early RT). Early RT was
      associated with significant improvement in survival (5-year OS, 21.9% vs. 19.1%;
      P = .01). On subgroup analysis, the survival advantage for early RT was
      significant for patients receiving hyperfractionated RT (5-year OS, 28.2% vs.
      21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs.
      18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT
      was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence
      interval [CI], 0.85-0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94
      1.04; P = .53). CONCLUSION: These data support the early initiation of
      hyperfractionated thoracic RT for nonmetastatic SCLC.

PMID- 27686972
TI  - L-DOPA in the hu man ovarian follicular fluid acts as an antioxidant factor on
      granulosa cells.
AB  - BACKGROUND: A previous study showed that dopamine (DA), which is contained in
      follicular fluid (FF) from IVF patients, strongly increased the production of
      reactive oxygen species (ROS) by cultured human granulosa cells (GCs). ROS,
      including H2O2, are assumed to play roles in ovarian physiology and pathology.
      Ovarian DA could be derived from the circulation, ovarian innervation and/or
      unknown ovarian sources. L-DOPA is the direct precursor of DA in its synthetic
      pathway. It was not yet described in FF. We examined L-DOPA levels in FF from IVF
      patients. As it may exert anti-oxidative and ROS-scavenging functions, we studied
      whether it exerts such actions in human GCs and whether DOPA-decarboxylase (DDC),
      the enzyme converting L-DOPA to DA, is expressed in the human ovary. RESULTS:
      ELISA measurements revealed that human IVF-derived FF contains L-DOPA. In
      cultured human GCs automated confluence analyses showed that L-DOPA enhanced
      their survival. This is in contrast to the actions of DA, which reduced cell
      survival. A dose-dependent mode of action of L-DOPA was identified using a
      fluorescent ROS indicator. The results showed that it antagonized intracellular
      ROS accumulation induced by exogenous H2O2. DDC was absent in follicular GCs, but
      immunohistochemistry identified it in theca cells (TCs) of large follicles in the
      human ovary. Laser micro-dissection followed by RT-PCR corroborated the
      expression. DDC was also identified in the steroidogenic cells of the corpus
      luteum. CONCLUSIONS: L-DOPA in FF is an antioxidant factor and exerts positive
      influences on GCs. Ovarian DA is derived from L-DOPA and has opposite actions.
      Exogenous L-DOPA is a standard therapy for Parkinson's disease, and the results
      raise the possibility that it may be able to exert positive actions as an
      antioxidant in ovarian conditions, as well.

PMID- 27686971
TI  - Phase 2 Study of Erlotinib in Combination With Linsitinib (OSI-906) or Placebo in
      Chemotherapy-Naive Patients With Non-Small-Cell Lung Cancer and Activating
      Epidermal Growth Factor Receptor Mutations.
AB  - INTRODUCTION: First-line epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor treatment of advanced non-small-cell lung cancer with EGFR-activating
      mutations improves outcomes compared with chemotherapy, but resistance develops
      in most patients. Compensatory signaling through type 1 insulin-like growth
      factor 1 receptor (IGF-1R) may contribute to resistance; dual blockade of IGF-1R
      and EGFR may improve outcomes. PATIENTS AND METHODS: We performed a randomized,
      double-blind, placebo-controlled phase II study of linsitinib, a dual IGF-1R and
      insulin receptor tyrosine kinase inhibitor, plus erlotinib versus placebo plus
      erlotinib in chemotherapy-naive patients with EGFR-mutation positive, advanced
      non-small-cell lung cancer. Patients received linsitinib 150 mg twice daily or
      placebo plus erlotinib 150 mg once daily on continuous 21-day cycles. The primary
      end point was progression-free survival. RESULTS: After randomization of 88
      patients (44 each arm), the trial was unblinded early owing to inferiority in the
      linsitinib arm. The median progression-free survival for the linsitinib versus
      the placebo group was 8.4 months versus 12.4 months (hazard ratio, 1.37; P =
      .29). Overall response rate (47.7% vs. 75.0%; P = .02) and disease control rate
      (77.3% vs. 95.5%; P = .03) were also inferior. Whereas most adverse events were
      <= grade 2, linsitinib plus erlotinib was associated with increased adverse
      events that led to decreased erlotinib exposure (median days, 228 vs. 305). No
      drug-drug interaction was suggested by pharmacokinetic and pharmacodynamic
      results. CONCLUSION: Adding linsitinib to erlotinib resulted in inferior outcomes
      compared with erlotinib alone. Further understanding of the signaling pathways
      and a biomarker that can predict efficacy is needed prior to further clinical
      development of IGF-1R inhibitors in lung cancer.

PMID- 27686974
TI  - HSP70 dependence in rhabdomyosarcoma: Seed or soil?

PMID- 27686973
TI  - TEMPO-Assisted Free Radical-Initiated Peptide Sequencing Mass Spectrometry (FRIPS
      MS) in Q-TOF and Orbitrap Mass Spectrometers: Single-Step Peptide Backbone
      Dissociations in Positive Ion Mode.
AB  - The present study demonstrates that one-step peptide backbone fragmentations can
      be achieved using the TEMPO [2-(2,2,6,6-tetramethyl piperidine-1-oxyl)]-assisted
      free radical-initiated peptide sequencing (FRIPS) mass spectrometry in a hybrid
      quadrupole time-of-flight (Q-TOF) mass spectrometer and a Q-Exactive Orbitrap
      instrument in positive ion mode, in contrast to two-step peptide fragmentation in
      an ion-trap mass spectrometer (reference Anal. Chem. 85, 7044-7051 (30)). In the
      hybrid Q-TOF and Q-Exactive instruments, higher collisional energies can be
      applied to the target peptides, compared with the low collisional energies
      applied by the ion-trap instrument. The higher energy deposition and the
      additional multiple collisions in the collision cell in both instruments appear
      to result in one-step peptide backbone dissociations in positive ion mode. This
      new finding clearly demonstrates that the TEMPO-assisted FRIPS approach is a very
      useful tool in peptide mass spectrometry research. Graphical Abstract ?.

PMID- 27686976
TI  - Highlights of WHO's work in the Eastern Mediterranean Region.

PMID- 27686975
TI  - Plasma triglyceride and high density lipoprotein cholesterol are poor surrogate
      markers of pro-atherogenic chylomicron remnant homeostasis in subjects with the
      metabolic syndrome.
AB  - BACKGROUND: Subjects with metabolic syndrome (MetS) exhibit impaired lipoprotein
      metabolism and have an increased risk of cardiovascular disease. Although the
      risk is attributed primarily to the risk associated with individual components,
      it is also likely affected by other associated metabolic defects. Remnants of
      postprandial lipoproteins show potent atherogenicity in cell and animal models of
      insulin resistance and in pre-diabetic subjects with postprandial dyslipidemia.
      However, few studies have considered regulation of chylomicron remnant
      homeostasis in MetS per se. This study measured the plasma concentration in
      Caucasian men and women of small dense chylomicrons following fasting and
      explored associations with metabolic and anthropometric measures. METHODS: A
      total of 215 Australian Caucasian participants (median age 62 years) were
      investigated. Of them, 40 participants were classified as having MetS.
      Apolipoprotein (apo) B-48, an exclusive marker of chylomicrons, metabolic markers
      and anthropometric measures were determined following an overnight fast. RESULTS:
      The fasting apo B-48 concentration was 40 % higher in subjects with MetS than
      those without MetS. In all subjects, triglyceride (r = 0.445, P < 0.0005), non
      HDL cholesterol (r = 0.28, P < 0.0005) and HDL cholesterol concentration (r = 
      0.272, P < 0.0005) were weakly associated with apo B-48 concentration. In
      subjects with MetS, the association of apo B-48 with triglyceride and non-HDL
      cholesterol was enhanced, but neither were robust markers of elevated apo B-48 in
      MetS (r = 0.618 and r = 0.595 respectively). There was no association between apo
      B-48 and HDL cholesterol in subjects with MetS. CONCLUSION: This study
      demonstrates a substantial accumulation of pro-atherogenic remnants in subjects
      with MetS. We have shown that in a Caucasian cohort, the fasting plasma
      concentration of triglyceride or HDL/non-HDL cholesterol serves as poor surrogate
      markers of atherogenic chylomicron remnants. These findings suggest that subjects
      with MetS exhibit a chronic defect in chylomicron metabolism that is likely to
      contribute to their increased CV risk.

PMID- 27686977
TI  - Deaths of children aged under 5 years and related factors in the Islamic Republic
      of Iran: a populationbased case-control study.
AB  - The study was conducted to determine the family, social and economic factors
      associated with deaths of children aged under 5 years. A registry-based nested
      case-control study was conducted of the deaths of all children aged under 5 years
      in Kohgilooyeh and Boyer-Ahmad Province in the Islamic Republic of Iran. For each
      death, two controls were randomly selected among children of the same age, sex
      and place of residence (186 cases and 372 controls). Congenital abnormality
      (37.6%) and preterm birth (29.0%) were the two most frequent causes of death
      among children aged under 5 years. No vaccine-preventable disease was reported as
      the cause of death. The strongest associations were found with consanguinity of
      the parents (OR = 3.92; 95% CI = 2.27-6.85 for being first cousins in comparison
      with no family relation; P < 0.001) and with domestic violence to the mother
      during pregnancy (OR = 3.13; 95% CI = 1.60-6.17; P < 0.01). The main causes of
      death of children aged under 5 years in the Province were congenital abnormality
      and prematurity.

PMID- 27686978
TI  - Collaboration between pharmacists and general practitioners in the health care
      system in the Islamic Republic of Iran.
AB  - Collaboration between pharmacists and general practitioners (GPs) has been shown
      to enhance patient care and outcomes. The aim of the present study was to
      investigate the collaborative working relationship between pharmacists and GPs in
      terms of their attitudes, role perceptions, experience with collaborative
      practice, preferred method of communication, areas of current and further
      collaboration, and perceived barriers to interprofessional collaboration in a
      sample of the Iranian population. We distributed 318 questionnaires to community
      pharmacists and GPs in Tehran. Both groups had a positive attitude towards
      collaboration; however, about half the respondents reported only occasional
      collaborative practice. Both groups preferred communication by telephone or face
      toface communication by fax or letter. Few current areas of collaboration were
      identified; however, an area favoured by both groups was "decision-making for
      patients' pharmacotherapy". The two groups expressed concern about possible
      fragmentation of patient care with the involvement of multiple health care
      providers, and perceived lack of face-to-face communication as a possible barrier
      to collaboration.

PMID- 27686979
TI  - Direct-to-consumer advertising for pharmaceuticals in Jordan from a gender
      perspective.
AB  - This study aimed to investigate the extent to which direct-to-consumer
      advertising (DTCA) for pharmaceuticals is disseminated in Jordan and to identify
      subsequent gender differences. The study was conducted on two samples: 1)
      patients (drug consumers) attending Jordan University Hospital, and 2) physicians
      working at the hospital (prescribers). A questionnaire was distributed to male
      and female patients (n=550), and based on its results a second questionnaire was
      designed and distributed to male and female physicians (n=200). The response rate
      was 93% for patients and 72% for physicians. Although the Jordanian Drug and
      Pharmacy Law prohibits the public promotion of medicines, consumers remain
      exposed to pharmaceutical advertising. The top ten drug classes advertised
      directly to consumers in Jordan included prescription-only drugs. Approximately
      45% of the two samples agreed that women were more likely to be targeted by DTCA,
      while only 2% of them believed that men are more likely to be targeted. However,
      there was no statistically significant gender difference in attitudes towards
      pharmaceutical DTCA and tools used.

PMID- 27686980
TI  - Burden and associated factors for caregivers of the elderly in a developing
      country.
AB  - The elderly population in South Asia is growing. In Pakistan trained caregivers
      are scarce and culturally not acceptable. This study assessed the level of stress
      experienced by caregivers of the elderly and determined the association of care
      giving burden with different characteristics of the elderly. A cross-sectional,
      questionnaire based study was conducted using nonprobability purposive sampling.
      All consenting participants aged 60 years and above needing help with at least
      one activity of daily living or two instrumental activities of daily living were
      included. 350 participants were assessed for perceived care giver burden. Care
      providers were mostly female (68.9%). Half (50.3%) of the caregivers had a
      positive score on a perceived care burden scale. Financial impact had a strong
      correlation (0.79) with perceived caregiver burden. Higher dependency levels of a
      physical and cognitive nature posed greater burden on caregivers. Behavioural
      issues of the elderly such as verbal abuse and difficulty sleeping were
      predictors of a higher caregiver burden. Caregiver burden is a significant issue
      for those caring for elderly family members in Karachi, Pakistan.

PMID- 27686981
TI  - Adherence of preventive oral care products in the Syrian market to evidence-based
      international recommendations.
AB  - No study has investigated the availability and adherence of preventive oral care
      products on the Syrian market to evidence-based international recommendations.
      Data were collected in 2012, and updated in 2016, in terms of availability,
      characteristics and adherence to evidence-based international recommendations.
      Few preventive products adhered to the recommendations. Despite the large
      decrease in the number of oral care products on the Syrian market, due to the
      Syrian crisis, nonadherence of some of the available products is still present. A
      multisectorial approach at a policy level is needed to address such important
      limitations. The Syrian Ministry of Health should reform regulations for fluoride
      products to become subject to drug monitoring systems; the Syrian Arab Committee
      for Measurements and Standards needs to update its standards; and the Syrian
      General Dental Association should distribute a preventive booklet to dental
      practitioners.

PMID- 27686982
TI  - Association between oral health knowledge and practices of Saudi pregnant women
      in Dammam, Saudi Arabia.
AB  - This study assessed the association between oral health knowledge and practices
      of pregnant Saudi women selected from visitors to a government hospital in
      Dammam, Saudi Arabia in 2014. Women answered questions on oral health knowledge
      during pregnancy and knowledge of infant oral health. Most women (> 70%) knew
      that dental caries in children can be prevented, that pregnancy affects oral
      health and that dental treatment during pregnancy can negatively affect infants.
      Most women (> 80%) performed oral hygiene procedures but only 18% regularly
      visited the dentist. In a regression analysis, oral health knowledge was not
      significantly associated with reported oral hygiene practices. Women who visited
      the dentist regularly were more likely to know how to prevent caries in children,
      and that dental treatment during pregnancy and infant health were associated.

PMID- 27686983
TI  - Primary healthcare reform in the United Nations Relief and Works Agency for
      Palestine Refugees in the Near East.
AB  - Palestinian refugees served by the United Nation Relief and Works Agency for
      Palestine Refugees in the Near East (UNRWA) are experiencing increasing rates of
      diagnosis of non-communicable diseases. In response, in 2011 UNRWA initiated an
      Agency-wide programme of primary healthcare reform, informed by the Chronic Care
      Model framework. Health services were reorganized following a family-centred
      approach, with delivery by multidisciplinary family health teams supported by
      updated technical advice. An inclusive clinical information system, termed e
      Health, was implemented to collect a wide range of health information, with a
      focus on continuity of treatment. UNRWA was able to bring about these wide
      ranging changes within its existing resources, reallocating finances, reforming
      its payment mechanisms, and modernizing its drug-procurement policies. While
      specific components of UNRWA's primary healthcare reform are showing promising
      results, additional efforts are needed to empower patients further and to
      strengthen involvement of the community.

PMID- 27686984
TI  - Microplastic fragments and microbeads in digestive tracts of planktivorous fish
      from urban coastal waters.
AB  - We investigated microplastics in the digestive tracts of 64 Japanese anchovy
      (Engraulis japonicus) sampled in Tokyo Bay. Plastic was detected in 49 out of 64
      fish (77%), with 2.3 pieces on average and up to 15 pieces per individual. All of
      the plastics were identified by Fourier transform infrared spectroscopy. Most
      were polyethylene (52.0%) or polypropylene (43.3%). Most of the plastics were
      fragments (86.0%), but 7.3% were beads, some of which were microbeads, similar to
      those found in facial cleansers. Eighty percent of the plastics ranged in size
      from 150 MUm to 1000 MUm, smaller than the reported size range of floating
      microplastics on the sea surface, possibly because the subsurface foraging
      behavior of the anchovy reflected the different size distribution of plastics
      between surface waters and subsurface waters. Engraulis spp. are important food
      for many humans and other organisms around the world. Our observations further
      confirm that microplastics have infiltrated the marine ecosystem, and that humans
      may be exposed to them. Because microplastics retain hazardous chemicals,
      increase in fish chemical exposure by the ingested plastics is of concern. Such
      exposure should be studied and compared with that in the natural diet.

PMID- 27686987
TI  - [Parental Monitoring and its Relation to Behaviour Problems and Risk Behaviour in
      an Adolescent School Sample].
AB  - Parental Monitoring and its Relation to Behaviour Problems and Risk Behaviour in
      an Adolescent School Sample Numerous research studies emphasize parental
      monitoring as a protective factor for adolescent problem behaviour. The purpose
      of the study presented was to use Stattin and Kerr's (2000) monitoring subscales
      for the first time in a German-speaking area and to explore the relations to
      behaviour problems in an adolescent school sample. The two active monitoring
      strategies "parental control" and "parental solicitation" as well as "parental
      knowledge" and "child disclosure" relating to behaviour problems and risk
      behaviour were examined. A sample of 494 pupils, grades 5, 7 and 9, of German
      secondary schools and their parents answered questions on "parental knowledge",
      "control", "solicitation" and "child disclosure". Adolescents also answered the
      German version of the Strengths and Difficulties Questionnaire (SDQ) and items
      about risk behaviour like frequency of violence, delinquency, substance abuse,
      self-injuring behaviour and school absenteeism. Behaviour problems in terms of
      the SDQ could be predicted sufficiently by "parental knowledge", but for the
      prediction of risk behaviour, the active parental monitoring strategies were of
      importance, too. More "parental knowledge", more "control" and less
      "solicitation" could predict less risk behaviour. Results confirm "parental
      knowledge" as a general protective factor for problem behaviour. However, they
      show the importance of "parental control" for adolescent risk behaviour.

PMID- 27686986
TI  - [Social-Emotional Competence in Young Children with Hearing, Visual or
      Intellectual Impairments - an Explorative Study with the ITSEA].
AB  - Social-Emotional Competence in Young Children with Hearing, Visual or
      Intellectual Impairments - an Explorative Study with the ITSEA Early emotional
      and social competence is considered as an important requirement for social
      participation in family and child care settings. We report on a study exploring
      the usefulness of the competence scales as a part of the "Infant-Toddler Social
      and Emotional Assessment" (ITSEA) for one- to three-year old children in a sample
      of 253 toddlers with hearing, visual or intellectual impairments. Internal
      consistency of the six scales is good (alpha > .86). An ANOVA reveals significant
      differences between the three groups and a correlation with additional
      disabilities. These explorative results support the development of a German
      standardization of the ITSEA.

PMID- 27686988
TI  - [The Therapy Process of Accompanying Mothers in Multiple Family Therapy Groups:
      Evidence from a German Child Psychiatric Setting].
AB  - The Therapy Process of Accompanying Mothers in Multiple Family Therapy Groups:
      Evidence from a German Child Psychiatric Setting This study provides an empirical
      contribution to the understanding of parents that accompany their children in
      psychiatric multiple family therapy settings (MFT). To this end, we conducted
      qualitative interviews with mothers that had successfully participated, with
      their diagnosed children (ages 3 to 9), in disorder-independent, age-homogeneous,
      and open family groups (the "Magdeburg Model") for several months. We performed a
      theoretical coding approach to the extensive interview material (n = 6
      interviews, duration = 70 to 100 minutes each) according to Grounded Theory and
      extracted seven main and 29 sub-categories. These categories yield a coherent,
      complete, and specific subjective therapy model for this setting. One of the
      central findings is a profound understanding of to what extent and by which means
      the family group as a social arena paves and supports the arrival of the mothers
      in the group, their engagement into the therapy process, and their motivational
      and volitional steps during therapy. Another relevant result is a reconstruction
      of what we termed Arriving Home, which is the epitome of the positive cognitive,
      affective, and behavioral therapeutic development that mothers perceive.
      Conclusions for clinical practice as well as for qualitative and mixed methods
      therapy research are discussed.

PMID- 27686995
TI  - Conscientious objection in healthcare, referral and the military analogy.
AB  - An analogy is sometimes drawn between the proper treatment of conscientious
      objectors in healthcare and in military contexts. In this paper, I consider an
      aspect of this analogy that has not, to my knowledge, been considered in debates
      about conscientious objection in healthcare. In the USA and elsewhere, tribunals
      have been tasked with the responsibility of recommending particular forms of
      alternative service for conscientious objectors. Military conscripts who have a
      conscientious objection to active military service, and whose objections are
      deemed acceptable, are required either to serve the military in a non-combat
      role, or assigned some form of community service that does not contribute to the
      effectiveness of the military. I argue that consideration of the role that
      military tribunals have played in determining the appropriate form of alternative
      service for conscripts who are conscientious objectors can help us to understand
      how conscientious objectors in healthcare ought to be treated. Additionally, I
      show that it helps us to address the vexed issue of whether or not conscientious
      objectors who refuse to provide a service requested by a patient should be
      required to refer that patient to another healthcare professional.

PMID- 27686996
TI  - Civic republican medical ethics.
AB  - This article develops a civic republican approach to medical ethics. It outlines
      civic republican concerns about the domination that arises from subjection to an
      arbitrary power of interference, while suggesting republican remedies to such
      domination in healthcare. These include proposals for greater review, challenge
      and pre-authorisation of medical power. It extends this analysis by providing a
      civic republican account of assistive arbitrary power, showing how it can create
      similar problems within both formal and informal relationships of care, and
      offering strategies for tackling it. Two important objections to civic republican
      medical ethics-that it overvalues independence and political participation in
      healthcare-are also considered and rebutted.

PMID- 27686997
TI  - When Are Risk Analyses on Job Titles Informative?

PMID- 27687000
TI  - Changes in antioxidant and antibacterial activities as well as phytochemical
      constituents associated with ginger storage and polyphenol oxidase activity.
AB  - BACKGROUND: Herbal materials should be stored at optimal conditions in order to
      retain their nutritional quality. Proper storage has a significant impact on the
      quality of the herbs and spices. METHODS: The effects of storage temperature (5
      and 15  degrees C) and time (4 and 8 months) on the phytochemical constituents
      associated with the antioxidant and antibacterial activities of ginger varieties
      (Halia bentong and Halia bara) were evaluated to determine the optimal storage
      conditions for ginger rhizomes. Total flavonoid content (TFC) and Total phenolic
      content (TPC) were measured using the spectrophotometric method. Individual
      phenolic acids and flavonoids, 6-gingerol and 6-shogaol were identified by ultra
      high performance liquid chromatography. Ferric reducing antioxidant potential
      (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were used for evaluation
      of antioxidant activities. An antibacterial property of ginger varieties was
      evaluated using well diffusion method. RESULTS: Dry matter, TPC, TFC and
      individual phenolics and flavonoids content, 6-gingerol and 6-shogaol content
      noticeably decreased at 5 and 15  degrees C during the storage times from 4 to 8
      months. Highest content of flavonoids, phenolic acids, 6-gingerol, and 6-shogaol
      was observed in fresh samples followed by rhizomes stored at 5  degrees C for 4
      months. Storage at 15  degrees C for 4 months reduced the phytochemical content
      significantly. Cinnamic acid and tannic acid were not detected in those variety
      stored at 15  degrees C for 4 and 8 months. Polyphenol oxidase (PPO) activity was
      associated significantly with storage time and temperature. Highest and lowest
      PPO activity was observed in stored and fresh rhizomes respectively. Antioxidant
      and antimicrobial activities gradually declined with the increase of storage
      temperature (from 5 to 15  degrees C) and duration (from 4 to 8 months) in both
      the varieties. Freshly harvested Halia bara variety had higher antioxidant and
      antibacterial activity compared to the Halia bentong variety. CONCLUSIONS: Halia
      bara exhibited valuable phytochemical content and antioxidant and antibacterial
      activities at higher levels compared to that exhibited by Halia bentong rhizomes.
      In general, storage of Malaysian ginger varieties at temperature of 5  degrees C
      is recommended and the storage time should be not more than 4 months. This
      storage condition will provide greater stability to the concentration of the
      phytochemical constituents more similar to the fresh material.

PMID- 27686998
TI  - Spatiotopic updating facilitates perception immediately after saccades.
AB  - As the neural representation of visual information is initially coded in
      retinotopic coordinates, eye movements (saccades) pose a major problem for visual
      stability. If no visual information were maintained across saccades, retinotopic
      representations would have to be rebuilt after each saccade. It is currently
      strongly debated what kind of information (if any at all) is accumulated across
      saccades, and when this information becomes available after a saccade. Here, we
      use a motion illusion to examine the accumulation of visual information across
      saccades. In this illusion, an annulus with a random texture slowly rotates, and
      is then replaced with a second texture (motion transient). With increasing
      rotation durations, observers consistently perceive the transient as large
      rotational jumps in the direction opposite to rotation direction (backward
      jumps). We first show that accumulated motion information is updated
      spatiotopically across saccades. Then, we show that this accumulated information
      is readily available after a saccade, immediately biasing postsaccadic
      perception. The current findings suggest that presaccadic information is used to
      facilitate postsaccadic perception and are in support of a forward model of
      transsaccadic perception, aiming at anticipating the consequences of eye
      movements and operating within the narrow perisaccadic time window.

PMID- 27686999
TI  - Biodegradable black phosphorus-based nanospheres for in vivo photothermal cancer
      therapy.
AB  - Photothermal therapy (PTT) offers many advantages such as high efficiency and
      minimal invasiveness, but clinical adoption of PTT nanoagents have been stifled
      by unresolved concerns such as the biodegradability as well as long-term
      toxicity. Herein, poly (lactic-co-glycolic acid) (PLGA) loaded with black
      phosphorus quantum dots (BPQDs) is processed by an emulsion method to produce
      biodegradable BPQDs/PLGA nanospheres. The hydrophobic PLGA not only isolates the
      interior BPQDs from oxygen and water to enhance the photothermal stability, but
      also control the degradation rate of the BPQDs. The in vitro and in vivo
      experiments demonstrate that the BPQDs/PLGA nanospheres have inappreciable
      toxicity and good biocompatibility, and possess excellent PTT efficiency and
      tumour targeting ability as evidenced by highly efficient tumour ablation under
      near infrared (NIR) laser illumination. These BP-based nanospheres combine
      biodegradability and biocompatibility with high PTT efficiency, thus promising
      high clinical potential.

PMID- 27687002
TI  - A picture is worth a thousand data points: an imagery dataset of paired shrub
      open microsites within the Carrizo Plain National Monument.
AB  - BACKGROUND: Carrizo Plain National Monument (San Joaquin Desert, California, USA)
      is home to many threatened and endangered species including the blunt-nosed
      leopard lizard (Gambelia sila). Vegetation is dominated by annual grasses, and
      shrubs such as Mormon tea (Ephedra californica), which is of relevance to our
      target species, the federally listed blunt-nosed leopard lizard, and likely also
      provides key ecosystem services. We used relatively nonintrusive camera traps, or
      trail cameras, to capture interactions between animals and these shrubs using a
      paired shrub-open deployment. Cameras were placed within the shrub understory and
      in open microhabitats at ground level to estimate animal activity and determine
      species presence. FINDINGS: Twenty cameras were deployed from April 1st, 2015 to
      July 5th, 2015 at paired shrub-open microsites at three locations. Over 425,000
      pictures were taken during this time, of which 0.4 % detected mammals, birds,
      insects, and reptiles including the blunt-nosed leopard lizard. Trigger rate was
      very high on the medium sensitivity camera setting in this desert ecosystem, and
      rates did not differ between microsites. CONCLUSIONS: Camera traps are an
      effective, less invasive survey method for collecting data on the presence or
      absence of desert animals in shrub and open microhabitats. A more extensive array
      of cameras within an arid region would thus be an effective tool to estimate the
      presence of desert animals and potentially detect habitat use patterns.

PMID- 27687001
TI  - Various nanoparticle morphologies and surface properties of waterborne
      polyurethane controlled by water.
AB  - Water plays important roles in organic reactions such as polyurethane synthesis,
      and the aqueous solution environment affects polymer morphology and other
      properties. This paper focuses on the morphology and surface properties of
      waterborne polyurethane resulting from the organic reaction in water involving
      different forms (solid and liquid), temperatures and aqueous solutions. We
      provide evidence from TEM observations that the appearance of polyurethane
      nanoparticles in aqueous solutions presents diverse forms, including imperfect
      spheres, perfect spheres, perfect and homogenous spheres and tubes. Based on the
      results on FTIR, GPC, AFM and XRD experiments, we suggest that the shape of the
      nanoparticles may be decided by the crimp degree (i.e., the degree of
      polyurethane chains intertangling in the water environment) and order degree,
      which are determined by the molecular weight (Mn) and hydrogen bonds. Meanwhile,
      solid water and high-temperature water can both reduce hard segments that gather
      on the polyurethane film surface to reduce hydrophilic groups and produce a soft
      surface. Our findings show that water may play key roles in aqueous polymer
      formation and bring order to molecular chains.

PMID- 27687003
TI  - Corrigendum: Effects of grazing on photosynthetic features and soil respiration
      of rangelands in the Tianshan Mountains of Northwest China.

PMID- 27687004
TI  - Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and
      PRDM1.
AB  - Plasmablastic lymphoma is an uncommon aggressive non-Hodgkin B-cell lymphoma type
      defined as a high-grade large B-cell neoplasm with plasma cell phenotype. Genetic
      alterations in MYC have been found in a proportion (~60%) of plasmablastic
      lymphoma cases and lead to MYC-protein overexpression. Here, we performed a
      genetic and expression profile of 36 plasmablastic lymphoma cases and demonstrate
      that MYC overexpression is not restricted to MYC-translocated (46%) or MYC
      amplified cases (11%). Furthermore, we demonstrate that recurrent somatic
      mutations in PRDM1 are found in 50% of plasmablastic lymphoma cases (8 of 16
      cases evaluated). These mutations target critical functional domains (PR motif,
      proline rich domain, acidic region, and DNA-binding Zn-finger domain) involved in
      the regulation of different targets such as MYC. Furthermore, these mutations are
      found frequently in association with MYC translocations (5 out of 9, 56% of cases
      with MYC translocations were PRDM1-mutated), but not restricted to those cases,
      and lead to expression of an impaired PRDM1/Blimp1alpha protein. Our data suggest
      that PRDM1 mutations in plasmablastic lymphoma do not impair terminal B-cell
      differentiation, but contribute to the oncogenicity of MYC, usually disregulated
      by MYC translocation or MYC amplification. In conclusion, aberrant coexpression
      of MYC and PRDM1/Blimp1alpha owing to genetic changes is responsible for the
      phenotype of plasmablastic lymphoma cases.

PMID- 27687005
TI  - Prognostic impact of MYC protein expression in central nervous system diffuse
      large B-cell lymphoma: comparison with MYC rearrangement and MYC mRNA expression.
AB  - The prognostic role of MYC has been well documented in non-central nervous system
      diffuse large B-cell lymphoma; however, it remains controversial in central
      nervous system diffuse large B-cell lymphoma. To investigate the prognostic value
      of MYC, we analyzed the MYC protein expression by immunohistochemistry, mRNA
      expression by RNA in situ hybridization, and gene status by fluorescence in situ
      hybridization in 74 cases of central nervous system diffuse large B-cell
      lymphoma. Moreover, we examined the correlation between MYC translocation, mRNA
      expression, and protein expression. The mean percentage of MYC immunopositive
      cells was 49%. Using a 44% cutoff value, 49 (66%) cases showed MYC protein
      overexpression. The result of mRNA in situ hybridization using the RNA scope
      technology was obtained using the H-scoring system; the median value was 34.2.
      Using the cutoff value of 63.5, 16 (22%) cases showed MYC mRNA overexpression.
      MYC gene rearrangement was detected in five out of 68 (7%) cases. MYC
      translocation showed no statistically significant correlation with mRNA
      expression; however, all MYC translocation-positive cases showed MYC protein
      overexpression, with a higher mean percentage of MYC protein expression than that
      of translocation-negative cases (78 vs 48%, P=0.001). The level of MYC mRNA
      expression was moderately correlated with the level of MYC protein expression
      (P<0.001). The mean percentage of MYC protein expression in the high MYC mRNA
      group was higher than that in the low MYC mRNA group (70 vs 47%, P<0.001). A
      univariate analysis showed that age over 60 years, Eastern Cooperative Oncology
      Group (ECOG) performance status >=2 and MYC protein overexpression were
      significantly associated with an increased risk of death. MYC translocation and
      MYC mRNA expression had no prognostic significance. On multivariate analysis, MYC
      protein overexpression and ECOG score retained prognostic significance.

PMID- 27687007
TI  - Phase-matched second harmonic generation with on-chip GaN-on-Si microdisks.
AB  - We demonstrate phase-matched second harmonic generation in gallium nitride on
      silicon microdisks. The microdisks are integrated with side-coupling bus
      waveguides in a two-dimensional photonic circuit. The second harmonic generation
      is excited with a continuous wave laser in the telecom band. By fabricating a
      series of microdisks with diameters varying by steps of 8 nm, we obtain a tuning
      of the whispering gallery mode resonances for the fundamental and harmonic waves.
      Phase matching is obtained when both resonances are matched with modes satisfying
      the conservation of orbital momentum, which leads to a pronounced enhancement of
      frequency conversion.

PMID- 27687008
TI  - Can Nursing Units With High Fall Rates Be Identified Using One Year of Data?
      Reliability of Fall Rates As a Function of the Number of Quarters on Which They
      Are Based.
AB  - Reliability-the extent to which multiple measurements of a target yield similar
      results-is critical in comparing healthcare provider quality. Hospital unit fall
      rates are widely tracked and used for benchmarking, but their reliability is not
      well-studied. Our twofold purpose was to estimate fall rate reliability, both in
      terms of signal (between-unit variability) relative to noise (within-unit
      variability) and in terms of the accuracy with which units can be classified as
      high-fall units; and to assess reliability as a function of the number of
      quarters of data used to compute fall rates. Using year 2013 data from 11,765
      critical care, step-down, medical, surgical, medical-surgical, and rehabilitation
      units in 1,552 US hospitals, we identified high-fall-rate units, computed units'
      signal-noise reliability, and simulated data to assess accuracy of high-fall-rate
      unit classification as a function of quarters of data. When critical care units
      were excluded, median unit type signal-noise reliabilities for annual total and
      injurious fall rates, respectively, ranged from .74 to .82 and from .53 to .68.
      In simulation, seven quarters of data were sufficient to achieve top-decile
      misclassification rates at or below 10% for all unit types except critical care.
      Top-quartile misclassification rates were higher; even 12 quarters of data did
      not consistently yield top-quartile misclassification rates below 10%. In the
      absence of long-term data, and for units with low patient volume and unit types
      with very low fall rates, comparison with a unit's own historical data may be
      more helpful for quality monitoring than attempting to rank it among its peers.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27687006
TI  - Fatty acid-binding protein 1 is preferentially lost in microsatellite instable
      colorectal carcinomas and is immune modulated via the interferon gamma pathway.
AB  - Fatty acid-binding protein 1 (FABP1) is an intracellular protein responsible for
      the transportation of long chain fatty acids. Aside from its functions in lipid
      metabolism and cellular differentiation, FABP1 also plays a role in inflammation
      through its interaction with peroxisome proliferator-activated receptors (PPARs).
      Previously, we compared expression of colonic epithelium genes in a subset of
      microsatellite instable (MSI) colorectal carcinomas (medullary carcinomas) to
      normal colonic mucosa and found that FABP1 expression was markedly decreased in
      the tumors. Further analysis of RNA expression in the colorectal subtypes and The
      Cancer Genome Atlas data set found that FABP1 expression is decreased in the CMS1
      subset of colorectal carcinomas, which is characterized by microsatellite
      instability. As MSI colorectal carcinomas are known for their robust immune
      response, we then aimed to link FABP1 to the immune microenvironment of MSI
      carcinomas. To confirm the gene expression results, we performed
      immunohistochemical analysis of a cohort of colorectal carcinomas. FABP1 was
      preferentially lost in MSI carcinomas (123/133, 93%) compared with microsatellite
      stable carcinomas (240/562, 43%, P<0.0001). In addition, higher numbers of tumor
      infiltrating lymphocytes were present in tumors with loss of FABP1 (P<0.0001).
      Decreased expression of the fatty acid storage and glucose regulator, PPARgamma,
      was associated with the loss of FABP1 (P<0.0001). Colorectal cancer cell lines
      treated with interferon gamma exhibited decreased expression of FABP1. FABP1
      expression was partially recovered with the treatment of the cell lines with
      rosiglitazone, a PPARgamma agonist. This study demonstrated that the loss of
      FABP1 expression is associated with MSI carcinomas and that interferon gamma
      stimulation plays a role in this process via its interaction with PPARgamma.

PMID- 27687009
TI  - A Green Approach to the Synthesis of alpha-Amino Phosphonate in Water Medium:
      Carbene Insertion into the N-H Bond by Cu(I) Catalyst.
AB  - Synthesis of amino phosphonates is more important owing to their significant
      applications in the biological systems. There are few methods already known in
      the literature to make these molecules; however, known methods have their own
      disadvantages. In this regard, synthesis of different kinds of amino phosphonates
      have been achieved via phosphonate substituted carbene insertion into the N-H
      bond of aniline catalyzed by readily available copper salt under mild reaction
      conditions in water. In order to find an efficient catalyst for carbene insertion
      reaction in neat water, a large number of transition metal catalysts were
      screened, and we found that the [Cu(CH3CN)4]ClO4 was the best catalyst under
      employed reaction conditions. Using this environmentally benign methodology
      (copper catalyzed reaction in water), a large number of biologically important
      amino phosphonates have been synthesized, isolated (37 examples), and
      characterized using standard analytical and spectroscopic techniques.

PMID- 27687010
TI  - Discrimination and internalised feelings experienced by people who stutter in
      Jordan.
AB  - PURPOSE: This study investigated the internalised feelings and discrimination
      experienced by people who stutter in Jordan. METHOD: Five adult speakers who
      stutter were interviewed as a focus group. The participants were asked about
      their feelings related to stuttering and discrimination. The participants'
      responses in the focus group and items adapted from the extant literature formed
      the basis of a 20-item questionnaire. The questionnaire was administered to 20
      additional adults who stutter to assess their internalised feelings about
      stuttering and their perceived rejecting behaviours (discrimination) associated
      with their impairment. RESULT: Feeling "annoyed" was the item that received the
      highest percentage of negative internalised feelings, followed by "embarrassed,"
      "shame," "disappointed," "nervous, "sad," "pessimistic," "fearful," "worried" and
      "lonely." The results of the discrimination experiences indicated that "getting a
      leadership position" was the item that most people who stutter reported being
      worried about, followed by "participation in the classroom," "getting a job,"
      "getting married," "being fully paid in their jobs," "teased," "promoted" and
      "renting a house." CONCLUSION: These findings provide further evidence of the
      universality that stuttering is more than the core surface features of speech,
      but also include aspects that exist below the surface such as negative
      internalised feelings and various discrimination experiences.

PMID- 27687011
TI  - Superficial malignant peripheral nerve sheath tumor with overlying intradermal
      melanocytic nevus mimicking spindle cell melanoma.
AB  - Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas with
      histological and immunohistochemical similarities to spindle cell melanoma.
      Although spindle cell melanoma is significantly more common, both tumors may
      express S100 and lack staining for HMB-45, Melan-A or MITF. Here we present a
      case of superficial malignant peripheral nerve sheath tumor with diffuse S100
      positivity arising in a subtle neurofibroma in close proximity to an intradermal
      melanocytic nevus. This configuration had led to prior misdiagnosis as a
      desmoplastic melanoma arising in the nevus and to sentinel lymph node biopsy.
      Identification of the background neurofibroma, as well as CD34 positivity raised
      consideration of a low grade malignant peripheral nerve sheath tumor, which was
      confirmed via observation of Schwannian differentiation on electron microscopy.
      The importance of distinguishing these two tumors is stressed owing to the
      difference in management.

PMID- 27687012
TI  - Impact of chromium dinicocysteinate supplementation on inflammation, oxidative
      stress, and insulin resistance in type 2 diabetic subjects: an exploratory
      analysis of a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Chromium dinicocysteinate (CDNC) is a unique chromium complex
      consisting of chromium, niacin, and L-cysteine. Previous preclinical and clinical
      studies support the safety and efficacy of CDNC in modulating oxidative stress,
      vascular inflammation, and glycemia in type 2 diabetes. OBJECTIVE: Herein, we
      report the results of several exploratory analyses conducted on type 2 diabetic
      subjects who previously participated in a 3-month randomized, double-blind,
      placebo-controlled trial and were treated with only metformin as standard
      diabetic care in addition to receiving the test supplementations. DESIGN: Results
      from 43 metformin users, who were randomly assigned to receive either placebo (P,
      n=13), chromium picolinate (CP, 400 ug elemental Cr(3+)/day, n=12), or CDNC (400
      ug elemental Cr(3+)/day, n=18), were analyzed for blood markers of vascular
      inflammation, insulin resistance, and oxidative stress at baseline and at 3
      months of supplementation. RESULTS: A statistically significant decrease in
      insulin resistance in the CDNC-supplemented cohort compared to placebo (p=0.01)
      was observed at 3 months. The CDNC group also demonstrated a significant
      reduction in insulin levels (p=0.03), protein carbonyl (p=0.02), and in TNF-alpha
      (p=0.03) compared to the placebo group. The CP group only showed a significant
      reduction in protein carbonyl levels (p=0.03) versus placebo. CONCLUSIONS: When
      controlling for diabetes medication, CDNC supplementation showed beneficial
      effects on blood markers of vascular inflammation, insulin resistance, and
      oxidative stress compared to placebo. The findings suggest that CDNC
      supplementation has potential as an adjunct therapy for individuals with type 2
      diabetes.

PMID- 27687013
TI  - Becoming Therapeutic Agents: A Grounded Theory of Mothers' Process When
      Implementing Cognitive Behavioural Therapy at Home with an Anxious Child.
AB  - : The premise of parent-centred programmes for parents of anxious children is to
      educate and train caregivers in the sustainable implementation of cognitive
      behaviour therapy (CBT) in the home. The existing operationalization of parent
      involvement, however, does not address the systemic, parent or child factors that
      could influence this process. The qualitative approach of grounded theory was
      employed to examine patterns of action and interaction involved in the complex
      process of carrying out CBT with one's child in one's home. A grounded theory
      goes beyond the description of a process, offering an explanatory theory that
      brings taken-for-granted meanings and processes to the surface. The theory that
      emerged from the analysis suggests that CBT implementation by mothers of anxious
      children is characterized by the evolution of mothers' perception of their child
      and mothers' perception of their role as well as a shift from reacting with
      emotion to responding pragmatically to the child. Changes occur as mothers
      recognize the crisis, make links between the treatment rationale, child's
      symptoms and their own parenting strategies, integrate tenets of CBT for anxiety
      and eventually focus on sustaining therapeutic gains through natural life
      transitions. The theory widens our understanding of mothers' role, therapeutic
      engagement, process, and decision-making. The theory also generates new
      hypotheses regarding parent involvement in the treatment of paediatric anxiety
      disorders and proposes novel research avenues that aim to maximize the benefits
      of parental involvement in the treatment of paediatric anxiety disorders.
      Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Mothers of
      anxious youth who take part in parent-centred programmes experience a shift in
      their perception of the child and of their role. Parental strategy after CBT
      implementation shifts from emotional empathy to cognitive empathy. Mothers
      experience significant challenges and require additional support in prevention of
      relapse and knowledge translation.

PMID- 27687014
TI  - Can pictures promote the acquisition of sight-word reading? An evaluation of two
      potential instructional strategies.
AB  - Sight-word instruction can be a useful supplement to phonics-based methods under
      some circumstances. Nonetheless, few studies have evaluated the conditions under
      which pictures may be used successfully to teach sight-word reading. In this
      study, we extended prior research by examining two potential strategies for
      reducing the effects of overshadowing when using picture prompts. Five children
      with developmental disabilities and two typically developing children
      participated. In the first experiment, the therapist embedded sight words within
      pictures but gradually faded in the pictures as needed using a least-to-most
      prompting hierarchy. In the second experiment, the therapist embedded text-to
      picture matching within the sight-word reading sessions. Results suggested that
      these strategies reduced the interference typically observed with picture prompts
      and enhanced performance during teaching sessions for the majority of
      participants. Text-to-picture matching also accelerated mastery of the sight
      words relative to a condition under which the therapist presented text without
      pictures.

PMID- 27687015
TI  - What are the Considerations in Balancing Benefits and Risks in Iron Treatment?:
      The Role for Newly Approved Iron Treatments.

PMID- 27687016
TI  - The prevalence and predictors of metabolically healthy obesity in obese rural
      population of China: a cross-sectional study.
AB  - Till now, no evidence illustrates the prevalence and predictors of metabolically
      healthy obesity (MHO) in rural areas of China. The objective of this study was,
      firstly, to examine the prevalence of MHO in rural areas of China, and identify
      contributing determinants of MHO, Secondly, to comprehensively investigate to the
      different characteristics between MHO and metabolically unhealthy obesity (MUO).
      We conducted a population-based cross-sectional study of 2037 participants with
      obesity in rural Liaoning Province during 2012-2013. Obesity was defined as BMI
      >=28 kg/m2 and metabolically healthy was defined as not having the metabolic
      syndrome. The prevalence of MHO was 23.1%, and significantly decreased with
      advancing age in female group. However there was no significant tendency with
      advancing age in male group. Independent determinant factors for MHO were age <55
      years (odds ratio [OR] 1.659; p = .001), non-current smoking (OR 1.397; p =
      .038), pre-menopause (OR 1.648; p = .030) and non-hyperuricemia (OR 2.317; p <
      .001), whereas race, gender, diet score, current drinking, marriage, sleep
      duration, hyperhomocysteinemia, levels of physical activity, annual income and
      educational status were not significant contributors. In conclusion, we found
      that age <55 years, non-current smoking, pre-menopause and non-hyperuricemia were
      identified as independent determinant factors for MHO in this population.

PMID- 27687017
TI  - Short and long time MR signal behavior of randomly distributed water and fat
      numerical simulations.
AB  - The MR time-signal behavior of water has been reported to be different on short
      and long time scales for systems of randomly distributed perturbers in water in
      the static dephasing regime. Up to now, the signal of the perturbers in such
      systems has not been taken into consideration. Water-fat emulsions are
      macroscopically homogeneous systems and can be considered as microscopically
      randomly distributed perturbing fat spheres embedded in water. In such water-fat
      systems, the signal of the perturber, fat, cannot be ignored. Since water and fat
      are within the same system, the fat signal behavior may show similarities with
      water, with differences in short and long time scales. This could complicate fat
      referenced MR thermometry (MRT) methods such as multi-gradient echo-based (MGE)
      MRT. Simulations were performed using a numerical phantom comprising spherical
      fat objects embedded in a spherical water medium. To characterize the fat signal,
      the theoretical signal description of water was fitted to the simulated fat
      signal. The simulated signals were sampled as an MGE signal and MGE MRT was used
      to calculate temperatures. The sampling was done with and without delay, to
      investigate the effect on the temperature error of the time ranges in which the
      signal was sampled. It was confirmed that the fat signal behavior was similar to
      that of water and consisted of two regimes. The separation between the short and
      long time scales was approximately at 55 ms for fat, as compared with 8.9 ms for
      water. Without delayed signal sampling, the MGE MRT temperature error was about
      2.5 degrees C. With delayed sampling such that both the water and the fat signals
      were either in the short or in the long time scale the error was reduced to 0.2
      degrees C.

PMID- 27687018
TI  - The future of Australia's Indigenous Population, 2011-61.
AB  - Existing projections of Australia's Indigenous Population suffer from a number of
      limitations: problematic input data, unsatisfactory projection model design, and
      poor forecast performance. The aim of this study was to create a new model for
      projecting that population that better represents the demographic processes at
      work, and that makes use of a newly available data source on identification
      change. A new projection model is presented that explicitly incorporates ethnic
      identification change, and mixed (Indigenous/Non-Indigenous) partnering and
      childbearing. It is a composite static-dynamic model which takes a multi-state
      form where data allow. The model was used to produce projections for the 2011-61
      period. Rapid growth of the Indigenous Population is expected, with population
      momentum, identification change, and mixed partnering and childbearing shown to
      contribute more to growth than above-replacement fertility and increasing life
      expectancy. The future growth of Australia's Indigenous Population is thus
      intimately connected to its interaction with the Non-Indigenous Population.

PMID- 27687019
TI  - Impaired decision-making and impulse control in Internet gaming addicts: evidence
      from the comparison with recreational Internet game users.
AB  - Although Internet games have been proven to be addictive, only a few game players
      develop online gaming addiction. A large number of players play online games
      recreationally without being addicted to it. These individuals are defined as
      recreational Internet gaming users (RGU). So far, no research has investigated
      decision-making and impulse control in RGU. In the current study, we used delay
      discounting (DD) task and probabilistic discounting (PD) task to examine decision
      making and impulse control in 20 healthy controls, 20 subjects with Internet
      gaming disorder (IGD) and 23 RGU during fMRI scanning. At the behavioral level,
      RGU showed lower DD rate and higher PD rate than subjects with IGD and there was
      no significant difference between RGU and healthy controls on the DD and PD
      rates. At the neural level, RGU showed increased neural response in the
      parahippocampal gyrus, the anterior cingulate cortex, the medial frontal gyrus
      and the inferior frontal gyrus as compared with subjects with IGD. These brain
      regions may play an important role in preventing RGU from developing addiction.
      The results suggest that the RGU are capable of inhibiting impulse due to
      additional cognitive endeavor and the subjects with IGD have deficit in decision
      making and impulsive control, which are associated with brain dysfunction.

PMID- 27687021
TI  - Lupus, antiphospholipid syndrome and epilepsy: an update.

PMID- 27687020
TI  - Long-term systemic lupus erythematosus disease control after allogeneic bone
      marrow transplantation.
AB  - Systemic lupus erythematosus (SLE), a disorder of the immune system, is
      potentially curable by allogeneic bone marrow transplantation (alloBMT). Until
      recently, alloBMT was limited by donor availability and toxicity. Reduced
      intensity conditioning (RIC) combined with post-transplantation cyclophosphamide
      (PTCy) has improved the availability and safety of alloBMT permitting its
      exploration in severe-refractory autoimmune illnesses. We report the six-year
      follow-up of a young female whose refractory SLE-associated nephrosis resolved
      after RIC alloBMT with PTCy.

PMID- 27687022
TI  - The prevalence of self-reported lower limb and foot health problems experienced
      by participants with systemic lupus erythematosus: Results of a UK national
      survey.
AB  - Objective The main aim of this survey was to determine the frequency of self
      reported lower limb or foot and ankle complications experienced by participants
      with systemic lupus erythematosus (SLE). A secondary aim was to determine the
      frequency of treatments that have been received or that participants with SLE may
      like to receive if offered. Method A quantitative, cross-sectional, self-reported
      survey design was utilized. The developed survey was checked for face and content
      validity prior to patient partner cognitive debriefing in order to ensure
      usability, understanding of the process of completion and of the questions posed.
      The full protocol for survey development has been published previously. Results
      This is the first comprehensive national UK survey of lower limb and foot health
      problems reported by participants with SLE. A high prevalence of vascular,
      dermatological and musculoskeletal complications was reported by survey
      respondents. Additionally, whilst the relative prevalence of sensory loss was
      low, a quarter of people reported having had a fall related to changes in foot
      sensation demonstrating a previously unknown rate and cause of falls. Conclusion
      Complications related to vascular, dermatological and musculoskeletal health are
      identified as particularly prevalent in participants with SLE. Further, there is
      a suggestion that the provision of interventions to maintain lower limb health is
      highly varied and lacks national standardization, despite there being a strong
      indication of participant reported need. The findings of this work can be used to
      inform care guideline development in addition to identifying areas for future
      research.

PMID- 27687023
TI  - Biological therapies in the treatment of cutaneous lupus erythematosus.
AB  - Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease occurring in
      association with or without systemic lupus erythematosus (SLE). Although
      antimalarials are widely used as the first-line systemic agent, refractory cases
      may benefit from additional immunomodulators, immunosuppressives, and biologics.
      An interest in biological therapies for CLE has emerged in recent years due to
      novel insight into the pathogenesis of CLE. These targets include B cells, T
      cells, and cytokines that are involved in immune system pathways. Currently
      belimumab is the only biological therapy approved for SLE and no biologic has
      been approved for CLE. While there is a paucity of high quality evidence with
      regard to biologics in CLE management, trials are currently being performed to
      determine their role.

PMID- 27687024
TI  - Complementary role of cardiovascular imaging and laboratory indices in early
      detection of cardiovascular disease in systemic lupus erythematosus.
AB  - Background Cardiovascular disease (CVD) has been documented in >50% of systemic
      lupus erythematosus (SLE) patients, due to a complex interplay between
      traditional risk factors and SLE-related factors. Various processes, such as
      coronary artery disease, myocarditis, dilated cardiomyopathy, vasculitis,
      valvular heart disease, pulmonary hypertension and heart failure, account for CVD
      complications in SLE. Methods Electrocardiogram (ECG), echocardiography (echo),
      nuclear techniques, cardiac computed tomography (CT), cardiovascular magnetic
      resonance (CMR) and cardiac catheterization (CCa) can detect CVD in SLE at an
      early stage. ECG and echo are the cornerstones of CVD evaluation in SLE. The
      routine use of cardiac CT and nuclear techniques is limited by radiation exposure
      and use of iodinated contrast agents. Additionally, nuclear techniques are also
      limited by low spatial resolution that does not allow detection of sub
      endocardial and sub-epicardial lesions. CCa gives definitive information about
      coronary artery anatomy and pulmonary artery pressure and offers the possibility
      of interventional therapy. However, it carries the risk of invasive
      instrumentation. Recently, CMR was proved of great value in the evaluation of
      cardiac function and the detection of myocardial inflammation, stress-rest
      perfusion defects and fibrosis. Results An algorithm for CVD evaluation in SLE
      includes clinical, laboratory, ECG and echo assessment as well as CMR evaluation
      in patients with inconclusive findings, persistent cardiac symptoms despite
      normal standard evaluation, new onset of life-threatening arrhythmia/heart
      failure and/or as a tool to select SLE patients for CCa. Conclusions A non
      invasive approach including clinical, laboratory and imaging evaluation is key
      for early CVD detection in SLE.

PMID- 27687025
TI  - 25-hydroxyvitamin D is associated with metabolic syndrome among premenopausal
      women with systemic lupus erythematosus in China.
AB  - Objectives This study aimed to investigate the status of 25-hydroxyvitamin D
      (25(OH)D) and its association with metabolic syndrome (MS) and different MS
      components among premenopausal women with systemic lupus erythematosus (SLE) in
      China. Patients and methods Altogether 113 premenopausal women with SLE and the
      age-matched healthy cohorts were recruited in this cross-sectional study.
      Clinical manifestations and laboratory data including serum 25(OH)D concentration
      were collected. A multivariable analysis was performed to analyze the association
      of 25(OH)D with MS and its components. Results The prevalence of 25(OH)D
      deficiency (25(OH)D < 20 ng/ml) and MS were common (24.8% and 30.1%,
      respectively) in premenopausal patients with SLE in China. Analysis of the
      association between 25(OH)D, MS and its components demonstrated that the lower
      level of 25(OH)D was associated with increased MS prevalence (OR = 0.920, p =
      0.012), a decreased level of high-density lipoprotein (OR = 1.059, p = 0.033) and
      a higher level of fasting glucose (OR = 0.810, p = 0.004). These associations
      were still detectible after adjustment for age, body mass index and SLE-related
      variables. Conclusion The level of 25(OH)D is associated with MS and its
      components in premenopausal women with SLE.

PMID- 27687026
TI  - Fatigue and cognitive function in systemic lupus erythematosus: associations with
      white matter microstructural damage. A diffusion tensor MRI study and meta
      analysis.
AB  - Objective The objective of this study was to investigate fatigue and cognitive
      impairments in systemic lupus erythematous (SLE) in relation to diffuse white
      matter microstructural brain damage. Methods Diffusion tensor MRI, used to
      generate biomarkers of brain white matter microstructural integrity, was obtained
      in patients with SLE and age-matched controls. Fatigue and cognitive function
      were assessed and related to SLE activity, clinical data and plasma biomarkers of
      inflammation and endothelial dysfunction. Results Fifty-one patients with SLE
      (mean age 48.8 +/- 14.3 years) were included. Mean diffusivity (MD) was
      significantly higher in all white matter fibre tracts in SLE patients versus age
      matched healthy controls ( p < 0.0001). Fatigue in SLE was higher than a normal
      reference range ( p < 0.0001) and associated with lower MD ( beta = -0.61, p =
      0.02), depression ( beta = 0.17, p = 0.001), anxiety ( beta = 0.13, p = 0.006)
      and higher body mass index ( beta = 0.10, p = 0.004) in adjusted analyses. Poorer
      cognitive function was associated with longer SLE disease duration ( p = 0.003)
      and higher MD ( p = 0.03) and, in adjusted analysis, higher levels of IL-6 ( beta
      = -0.15, p = 0.02) but not with MD. Meta-analysis (10 studies, n = 261, including
      the present study) confirmed that patients with SLE have higher MD than controls.
      Conclusion Patients with SLE have more microstructural brain white matter damage
      for age than the general population, but this does not explain increased fatigue
      or lower cognition in SLE. The association between raised IL-6 and worse current
      cognitive function in SLE should be explored in larger datasets.

PMID- 27687027
TI  - Lupus nephritis is associated with more corticosteroid-associated organ damage
      but less corticosteroid non-associated organ damage.
AB  - Objective The objective of this study was to investigate the association of lupus
      nephritis on organ damage and mortality in patients with systemic lupus
      erythematosus (SLE). Methods A total of 1112 patients with SLE were investigated.
      Lupus nephritis was defined as a proteinuria based on the 1997 American College
      of Rheumatology criteria. Damage was assessed using the Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage
      Index. The associations of lupus nephritis with overall, non-renal,
      corticosteroid-associated, and non-associated damage were analyzed using logistic
      regression. The age-adjusted and sex-adjusted standardized mortality ratio was
      evaluated in patients with and without lupus nephritis. Results The prevalence of
      lupus nephritis in patients with SLE was 46.3%. Patients with lupus nephritis had
      a higher percentage of overall cumulative damage than patients without lupus
      nephritis (51.5% vs. 35.7%, p < 0.001). The odds ratio was 1.40 after adjusting
      for age at SLE diagnosis, sex, disease duration, anti-malarial agents,
      immunosuppressive agents and cumulative corticosteroid dose. Among non-renal
      damage, the odds of corticosteroid-associated damage were higher (2.06, 95%
      confidence interval (CI) 1.43-2.96) whereas the odds of non-associated damage
      were lower (0.50, 95% CI 0.35-0.75) in patients with lupus nephritis. The
      standardized mortality ratios of patients with and without lupus nephritis were
      5.17 (95% CI 3.49-7.38) and 2.32 (95% CI 1.47-3.48), respectively. Conclusion In
      patients with SLE, the presence of lupus nephritis is associated with increased
      corticosteroid-associated damage but less corticosteroid non-associated damage.
      Also, mortality is significantly higher in patients with lupus nephritis than in
      those without lupus nephritis.

PMID- 27687030
TI  - CCGs must engage with public on potential service closures, says new guidance.

PMID- 27687028
TI  - Breast cancer in systemic lupus.
AB  - Objective There is a decreased breast cancer risk in systemic lupus erythematosus
      (SLE) versus the general population. We assessed a large sample of SLE patients,
      evaluating demographic and clinical characteristics and breast cancer risk.
      Methods We performed case-cohort analyses within a multi-center international SLE
      sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients,
      relative to demographics, reproductive history, family history of breast cancer,
      and time-dependent measures of anti-dsDNA positivity, cumulative disease
      activity, and drugs, adjusted for SLE duration. Results There were 86 SLE breast
      cancers and 4498 female SLE cancer-free controls. Patients were followed on
      average for 7.6 years. Versus controls, SLE breast cancer cases tended to be
      white and older. Breast cancer cases were similar to controls regarding anti
      dsDNA positivity, disease activity, and most drug exposures over time. In
      univariate and multivariate models, the principal factor associated with breast
      cancers was older age at cohort entry. Conclusions There was little evidence that
      breast cancer risk in this SLE sample was strongly driven by any of the clinical
      factors that we studied. Further search for factors that determine the lower risk
      of breast cancer in SLE may be warranted.

PMID- 27687029
TI  - Urinary sediment suggests lupus nephritis histology.
AB  - Objectives The objective of this paper was to evaluate correlations between
      kidney biopsy indexes (activity and chronicity) and urinary sediment findings;
      the secondary objective was to find which components of urinary sediment can
      discriminate proliferative from other classes of lupus nephritis. Methods Lupus
      nephritis patients scheduled for a kidney biopsy were included in our study. The
      morning before the kidney biopsy, we took urine samples from each patient.
      Receiver operating characteristic (ROC) curves were plotted to determine the area
      under the curve (AUC) of each test for detecting proliferative lupus nephritis; a
      classification tree was calculated to select a set of values that best-predicted
      lupus nephritis classes. Results We included 51 patients, 36 of whom were women
      (70.6%). Correlations of lupus nephritis activity index with the counts in the
      urinary sediment of erythrocytes (isomorphic and dysmorphic), acanthocytes, and
      leukocytes were 0.65 ( p < 0.0001) 0.62 ( p < 0.0001) and 0.22 ( p = 0.1228),
      respectively. Correlations of lupus nephritis chronicity index with the counts of
      erythrocytes, acanthocytes, and leukocytes were 0.60 ( p <= 0.0001), 0.52 ( p =
      0.0001) and 0.17 ( p = 0.2300), respectively. Our classification tree had an
      accuracy of 84.3%. Conclusions Evaluation of urine sediment reflects lupus
      nephritis histology.

PMID- 27687033
TI  - Russia's generalising HIV epidemic.

PMID- 27687032
TI  - Impact of bromocriptine-QR therapy on cardiovascular outcomes in type 2 diabetes
      mellitus subjects on metformin.
AB  - OBJECTIVES: Type 2 diabetes mellitus (T2DM) is associated with a substantially
      increased risk of cardiovascular disease (CVD). Bromocriptine-QR (B-QR), a quick
      release sympatholytic dopamine D2 receptor agonist, is a FDA-approved therapy for
      T2DM which may provide CVD risk reduction. Metformin is considered to be an agent
      with a potential cardioprotective benefit. This large placebo controlled clinical
      study assessed the impact of B-QR addition to existing metformin therapy on CVD
      outcomes in T2DM subjects. METHODS: 1791 subjects (1208 B-QR; 583 placebo) on
      metformin +/- another anti-diabetes therapy at baseline derived from the Cycloset
      Safety Trial, a 12-month, randomized, multicenter, placebo-controlled, double
      blind study in T2DM, were included in this study. The primary CVD endpoint
      evaluated was treatment impact on CVD event rate, prespecified as a composite of
      time to first myocardial infarction, stroke, coronary revascularization, or
      hospitalization for unstable angina/congestive heart failure. Impact on glycemic
      control was evaluated as a secondary analysis. RESULTS: The composite CVD end
      point occurred in 16/1208 B-QR treated (1.3%) and 18/583 placebo treated (3.1%)
      subjects resulting in a 55% CVD hazard risk reduction (intention-to-treat, Cox
      regression analysis; HR: 0.45 [0.23-0.88], p = 0.028). Kaplan-Meier curves
      demonstrated a significantly lower cumulative incidence rate of the CVD endpoint
      in the B-QR treatment group (Log-Rank p = 0.017). In subjects with poor glycemic
      control (HbA1c >= 7.5) at baseline, B-QR therapy relative to placebo resulted in
      a significant mean %HbA1c reduction of -0.59 at week 12 and -0.51 at week 52
      respectively (p < 0.001 for both) and a 10 fold higher percent of subjects
      achieving HbA1c goal of <=7% by week 52 (B-QR 30%, placebo 3%; p = 0.003).
      CONCLUSION: These findings suggest that in T2DM subjects on metformin, BQR
      therapy may represent an effective strategy for reducing CVD risk. Cycloset
      Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676.

PMID- 27687031
TI  - Transgenic expression of phytase in wheat endosperm increases bioavailability of
      iron and zinc in grains.
AB  - Phytate is a major constituent of wheat seeds and chelates metal ions, thus
      reducing their bioavailability and so the nutritional value of grains. Transgenic
      plants expressing heterologous phytase are expected to enhance degradation of
      phytic acid stored in seeds and are proposed to increase the in vitro
      bioavailability of mineral nutrients. Wheat transgenic plants expressing
      Aspergillus japonicus phytase gene (phyA) in wheat endosperm were developed till
      T3 generation. The transgenic lines exhibited 18-99 % increase in phytase
      activity and 12-76 % reduction of phytic acid content in seeds. The minimum
      phytic acid content was observed in chapatti (Asian bread) as compared to flour
      and dough. The transcript profiling of phyA mRNA indicated twofold to ninefold
      higher expression as compared to non transgenic controls. There was no
      significant difference in grain nutrient composition of transgenic and non
      transgenic seeds. In vitro bioavailability assay for iron and zinc in dough and
      chapatti of transgenic lines revealed a significant increase in iron and zinc
      contents. The development of nutritionally enhanced cereals is a step forward to
      combat nutrition deficiency for iron and zinc in malnourished human population,
      especially women and children.

PMID- 27687034
TI  - Transparency of participant incentives in HIV research.

PMID- 27687035
TI  - HIV testing and human rights: the right to the right test.

PMID- 27687037
TI  - Corrections.

PMID- 27687036
TI  - Is surgical preadmission an underused opportunity in HIV?

PMID- 27687038
TI  - Legal impediments to prevention.

PMID- 27687039
TI  - Need for robust and inclusive public health ethics review of the monitoring of
      HIV phylogenetic clusters for HIV prevention.

PMID- 27687040
TI  - From sharing needles to unprotected sex: a new wave of HIV infections in Iran?

PMID- 27687041
TI  - Temporal Regularity Detection and Rate Discrimination in Cochlear-Implant
      Listeners.
AB  - Cochlear implants (CIs) convey fundamental-frequency information using primarily
      temporal cues. However, temporal pitch perception in CI users is weak and, when
      measured using rate discrimination tasks, deteriorates markedly as the rate
      increases beyond 300 pulses-per-second. Rate pitch may be weak because the
      electrical stimulation of the surviving neural population of the implant
      recipient may not allow accurate coding of inter-pulse time intervals. If so,
      this phenomenon should prevent listeners from detecting when a pulse train is
      physically temporally jittered. Performance in a jitter detection task was
      compared to that in a rate-pitch discrimination task. Stimuli were delivered
      using direct stimulation in cochlear implants, on a mid-array and an apical
      electrode, and at two different rates (100 and 300 pps). Average performance on
      both tasks was worse at the higher pulse rate and did not depend on electrode.
      However, there was a large variability across and within listeners that did not
      correlate between the two tasks, suggesting that rate-pitch judgement and
      regularity detection are to some extent limited by task-specific processes.
      Simulations with filtered pulse trains presented to NH listeners yielded broadly
      similar results, except that, for the rate discrimination task, the difference
      between performance with 100- and 300-pps base rates was smaller than observed
      for CI users.

PMID- 27687042
TI  - Simvastatin enhances the hippocampal klotho in a rat model of streptozotocin
      induced cognitive decline.
AB  - Brain oxidative status is a crucial factor in the development of sporadic
      Alzheimer's disease (AD). Klotho, an anti-aging protein, diminishes oxidative
      stress by the induction of manganese superoxide dismutase (MnSOD). Thus, the
      substances that increase klotho expression could be considered as a potential
      treatment for Alzheimer's disease when the oxidative imbalance is present.
      Statins are suggested to up-regulate klotho expression. We examined the effect of
      simvastatin (5mg/kg, daily for 3weeks) on hippocampal klotho and MnSOD expression
      in the cognitive declined animal model induced by intracerebroventricular (ICV)
      streptozotocin (STZ) administration. Cognitive assessment was performed by the
      Morris Water Maze (MWM) test. The results indicated that mean escape latency and
      distance were prolonged in the ICV-STZ group compared with the control group. The
      expression of klotho and MnSOD were also down regulated in the hippocampus.
      Furthermore, improved spatial performance was observed in simvastatin-treated
      animals. This effect could be related to increase in oxidative stress tolerance
      as evidenced by klotho and MnSOD up-regulation. Our current study indicates that
      klotho upregulation may be a neuroprotective mechanism of simvastatin against
      cognitive decline in AD.

PMID- 27687043
TI  - Different association between specific manifestations of bruxism and
      temporomandibular disorder pain.
AB  - INTRODUCTION: A growing body of evidence suggests that bruxism exists in two
      separate manifestations. However, little is known about the association between
      specific manifestations of bruxism and temporomandibular disorder (TMD) pain.
      AIM: The aim of our study was to analyze the association between TMD pain and
      specific diagnoses of bruxism (sleep, awake, and mixed diagnosis of sleep and
      awake bruxism). MATERIAL AND METHODS: 508 adult patients (296 women and 212 men),
      aged between 18 and 64 years (mean age 34+/-12 years), attending to a clinic for
      general dental treatment. Patients were asked to fill an anonymous questionnaire,
      consisting of three questions, verifying the presence of TMD pain and two forms
      of bruxism. All questions were based on the Polish version of the Research
      Diagnostic Criteria for Temporomandibular Disorders patient history
      questionnaire. Cross tabulation was done, and chi2 was used as a test of
      significance to find the association between the variables. RESULTS: Awake
      bruxism was associated with TMD pain only in men (chi2=7.746, p<0.05) while mixed
      diagnosis of bruxism was associated with TMD pain in both women (chi2=10.486,
      p<0.05) and men (chi2=4.314, p<0.05). There was no statistically significant
      association between sleep bruxism and TMD pain. Gender-related differences in the
      presence of all bruxism diagnoses were also statistically insignificant.
      CONCLUSIONS: Interaction between sleep and awake bruxism may increase the risk
      for TMD pain. We suggest considering concomitance as a confounder, when studying
      sleep or awake bruxism.

PMID- 27687045
TI  - European Federation of Internal Medicine.

PMID- 27687044
TI  - Feasibility and outcomes of interventional treatment for vascular access site
      complications following transfemoral aortic valve implantation.
AB  - BACKGROUND: Despite the completion of more than 60,000 transcutaneous aortic
      valve implantations (TAVI) per year and an approximately 10-15 % incidence of
      vascular access site complications (VAC), there is a paucity of data on the
      efficacy and safety of percutaneous VAC treatment. HYPOTHESIS: Percutaneous
      endovascular treatment will be an effective treatment of VAC and associated with
      a low rate of surgical repair. Despite stent placement in proximity to the hip
      joint, endovascular treatment will be only rarely associated with disabling
      symptoms or complications. METHODS: We conducted a retrospective database
      analysis including 355 patients who underwent TAVI from January 2011 to October
      2015. To facilitate the detection of secondary complications of interventional
      VAC repair, we conducted structured telephone interviews with a focus on new
      diagnoses or symptoms of peripheral artery disease. RESULTS: Only four patients
      (1.1 %) required surgical treatment for VAC. Percutaneous balloon angioplasty
      (PTA) or stent implantation was required for VAC in 44 patients (12.4 %). The
      technical success rate of percutaneous VAC treatment was 93 %. Four patients died
      within 30 days of VAC treatment, but only one fatality was directly attributable
      to VAC. Post procedure mean hospital stay was numerically prolonged by 2.4 days
      in the VAC treatment group (P = 0.06). During a median follow-up of 385 days
      (range 89-909 days) none of the patients were diagnosed with a late VAC or
      reported a new diagnosis or symptoms of perfusion deficit or peripheral artery
      disease. CONCLUSION: Percutaneous treatment of VAC during TAVI is safe and
      effectively helps to minimize the need for surgery in the vast majority of VAC.
      During short- and mid-term follow-up, percutaneous VAC management is associated
      with low complication rates and good clinical outcomes.

PMID- 27687048
TI  - Superior mesenteric artery dissection does not necessarily mean acute mesenteric
      ischemia.

PMID- 27687047
TI  - Incidence of infusion reactions to anti-neoplastic agents in early phase clinical
      trials: The MD Anderson Cancer Center experience.
AB  - Infusion reactions (IRs) to anti-neoplastic agents require prompt recognition and
      immediate treatment to avert significant complications. We conducted a
      retrospective review of the medical records of consecutive patients who received
      anti-neoplastic therapy in the outpatient treatment center of the Department of
      Investigational Cancer Therapeutics from January 1, 2013 to November 30, 2013. Of
      the 597 patients who received treatment, 9 (1.5 %) had IRs (all <= grade 2). The
      most common IRs observed on first occurrence were chills (n = 5), itching, rash,
      and facial flushing (n = 3 each). There were no IR-related deaths. All the IRs
      were reversible with appropriate symptomatic treatment and the therapy was
      completed after temporary cessation of infusion in 7 of the 9 patients. The
      infusion was stopped in 2 patients due to symptoms suggestive of IgE-mediated
      allergic reaction and cytokine storm. Five of the 8 patients who were re
      challenged with the same therapy developed a similar reaction. However, the
      infusion was completed in 4 of the 5 patients after administration of intravenous
      diphenhydramine and/or hydrocortisone, or slowing the rate of infusion. And,
      subsequent cycles with the same agents were uneventful. IRs to anti-neoplastic
      agents are rare. Though the clinical presentations are overlapping, most IRs are
      not IgE-mediated allergic reactions. Appropriate premedication and slow rate of
      infusion facilitates uneventful administration of the anti-neoplastic agents in
      subsequent cycles. Further study in a larger cohort of patients to identify
      biomarkers of hypersensitivity is warranted.

PMID- 27687049
TI  - Cardiology consultation reduces provocative testing rates in an ED observation
      unit.
AB  - BACKGROUND: In evaluating patients with chest pain, emergency department
      observation units (EDOUs) may use a staffing model in which emergency physicians
      determine patient testing (EP model) or a model similar to a chest pain unit
      (CPU) in which cardiologists determine provocative testing (CPU model). METHODS:
      We performed a prospective study with 30-day telephone follow-up for all chest
      pain patients placed in our EDOU. Halfway through the study period, our EDOU
      transitioned from an EP model to a CPU model. We compared provocative testing
      rates and outcomes between the 2 models. RESULTS: Over the 34-month study period,
      our EDOU evaluated 1190 patients for chest pain. Patients placed in the EDOU
      during the 17-month CPU model were more likely to be moderate risk (Thrombolysis
      in Myocardial Infarction score 3-5) than those during the 17-month EP model:
      24.9% vs 18.8%, P = .011. Despite this difference, rates of provocative testing
      (stress testing or coronary computed tomography) were lower during the CPU model:
      47.1% vs 56.5%, P = .001. This reduction was particularly evident among low-risk
      patients (Thrombolysis in Myocardial Infarction score 0-2): 49.8% vs 58.1%, P =
      .011. Rates of myocardial infarction, percutaneous coronary intervention, or
      coronary artery bypass graft were similar between the 2 groups (2.8% vs 3.2%, P =
      .140). We noted no significant events or missed diagnoses in either group during
      the 30-day follow-up. CONCLUSION: An EDOU model that used mandatory cardiology
      consultation resulted in decreased provocative testing, particularly among low
      risk chest pain patients. Future research should explore the cost-effectiveness
      of this model.

PMID- 27687050
TI  - A dedicated palliative care nurse improves access to palliative care and hospice
      services in an urban ED.

PMID- 27687052
TI  - Meta-Analysis Comparing Established Risk Prediction Models (EuroSCORE II, STS
      Score, and ACEF Score) for Perioperative Mortality During Cardiac Surgery.
AB  - A wide variety of multivariable risk models have been developed to predict
      mortality in the setting of cardiac surgery; however, the relative utility of
      these models is unknown. This study investigated the literature related to
      comparisons made between established risk prediction models for perioperative
      mortality used in the setting of cardiac surgery. A systematic review was
      conducted to capture studies in cardiac surgery comparing the relative
      performance of at least 2 prediction models cited in recent guidelines (European
      System for Cardiac Operative Risk Evaluation [EuroSCORE II], Society for Thoracic
      Surgeons 2008 Cardiac Surgery Risk Models [STS] score, and Age, Creatinine,
      Ejection Fraction [ACEF] score) for the outcomes of 1-month or inhospital
      mortality. For articles that met inclusion criteria, we extracted information on
      study design, predictive performance of risk models, and potential for bias. Meta
      analyses were conducted to calculate a summary estimate of the difference in AUCs
      between models. We identified 22 eligible studies that contained 33 comparisons
      among the above models. Meta-analysis of differences in AUCs revealed that the
      EuroSCORE II and STS score performed similarly (with a summary difference in AUC
      = 0.00), while outperforming the ACEF score (with summary differences in AUC of
      0.10 and 0.08, respectively, p <0.05). Other metrics of discrimination and
      calibration were presented less consistently, and no study presented any metric
      of reclassification. Small sample size and absent descriptions of missing data
      were common in these studies. In conclusion, the EuroSCORE II and STS score
      outperform the ACEF score on discrimination.

PMID- 27687051
TI  - Effect of Body Mass Index on Left Ventricular Mass in Career Male Firefighters.
AB  - Left ventricular (LV) mass is a strong predictor of cardiovascular disease (CVD)
      events; increased LV mass is common among US firefighters and plays a major role
      in firefighter sudden cardiac death. We aim to identify significant predictors of
      LV mass among firefighters. Cross-sectional study of 400 career male firefighters
      selected by an enriched randomization strategy. Weighted analyses were performed
      based on the total number of risk factors per subject with inverse probability
      weighting. LV mass was assessed by echocardiography (ECHO) and cardiac magnetic
      resonance, and normalized (indexed) for height. CVD risk parameters included
      vital signs at rest, body mass index (BMI)-defined obesity, obstructive sleep
      apnea risk, low cardiorespiratory fitness, and physical activity. Linear
      regression models were performed. In multivariate analyses, BMI was the only
      consistent significant independent predictor of LV mass indexes (all, p <0.001).
      A 1-unit decrease in BMI was associated with 1-unit (g/m1.7) reduction of LV
      mass/height1.7 after adjustment for age, obstructive sleep apnea risk, and
      cardiorespiratory fitness. In conclusion, after height-indexing ECHO-measured and
      cardiac magnetic resonance-measured LV mass, BMI was found to be a major driver
      of LV mass among firefighters. Our findings taken together with previous research
      suggest that reducing obesity will improve CVD risk profiles and decrease on-duty
      CVD and sudden cardiac death events in the fire service. Our results may also
      support targeted noninvasive screening for LV hypertrophy with ECHO among obese
      firefighters.

PMID- 27687053
TI  - DNA methyltransferases exhibit dynamic expression during spermatogenesis.
AB  - DNA methylation is one of the epigenetic marks and plays critically important
      functions during spermatogenesis in mammals. DNA methylation is catalysed by DNA
      methyltransferase (DNMT) enzymes, which are responsible for the addition of a
      methyl group to the fifth carbon atom of the cytosine residues within cytosine
      phosphate-guanine (CpG) and non-CpG dinucleotide sites. Structurally and
      functionally five different DNMT enzymes have been identified in mammals,
      including DNMT1, DNMT2, DNMT3A, DNMT3B and DNMT3L. These enzymes mainly play
      roles in two DNA methylation processes: maintenance and de novo. While DNMT1 is
      primarily responsible for maintenance methylation via transferring methyl groups
      to the hemi-methylated DNA strands following DNA replication, both DNMT3A and
      DNMT3B are capable of methylating unmodified cytosine residues, known as de novo
      methylation. However, DNMT3L indirectly participates in de novo methylation, and
      DNMT2 carries out methylation of the cytosine 38 in the anticodon loop of
      aspartic acid transfer RNA. To date, many studies have been performed to
      determine spatial and temporal expression levels and functional features of the
      DNMT in the male germ cells. This review article comprehensively discusses
      dynamic expression of the DNMT during spermatogenesis and their relationship with
      male infertility development in the light of existing investigations.

PMID- 27687054
TI  - Effects of Trans-Resveratrol on hyperglycemia-induced abnormal spermatogenesis,
      DNA damage and alterations in poly (ADP-ribose) polymerase signaling in rat
      testis.
AB  - Diabetes induces oxidative stress, DNA damage and alters several intracellular
      signaling pathways in organ systems. This study investigated modulatory effects
      of Trans-Resveratrol on type 1 diabetes mellitus (T1DM)-induced abnormal
      spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase
      (PARP) signaling in rat testis. Trans-Resveratrol administration (5mg/kg/day, ip)
      to Streptozotocin-induced T1DM adult male Wistar rats from day 22-42 resulted in
      recovery of induced oxidative stress, abnormal spermatogenesis and inhibited DNA
      synthesis, and led to mitigation of 8-hydroxy-2'-deoxyguanosine formation in the
      testis and spermatozoa, and DNA double-strand breaks in the testis. Trans
      Resveratrol aggravated T1DM-induced up-regulation of aminoacyl tRNA synthetase
      complex-interacting multifunctional protein 2 expression; however, it did not
      modify the up-regulated total PARP and down-regulated PARP1 expressions, but
      recovered the decreased SirT1 (Sirtuin 1) levels in T1DM rat testis. Trans
      Resveratrol, when given alone, reduced the poly (ADP-ribosyl)ation (pADPr)
      process in the testis due to an increase in PAR glycohydrolase activity, but when
      given to T1DM rats it did not affect the pADPr levels. T1DM with or without Trans
      Resveratrol did not induce nuclear translocation of apoptosis-inducing factor and
      the formation of 50 kb DNA breaks, suggesting to the lack of caspase-3
      independent cell death called parthanatos. T1DM with or without Trans-Resveratrol
      did not increase necrotic cell death in the testis. Primary spermatocytes,
      Sertoli cells, Leydig cells and intra-testicular vessels showed the expression of
      PARP pathway related proteins. In conclusion, Trans-Resveratrol mitigates T1DM
      induced sperm abnormality and DNA damage, but does not significantly modulate
      PARP signaling pathway, except the SirT1 expression, in the rat testis.

PMID- 27687055
TI  - Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats by the
      regulation of inflammatory and apoptotic proteins.
AB  - Serotonin level plays a role in suppressing the pathological findings of benign
      prostatic hyperplasia (BPH). Thus a new selective serotonin reuptake inhibitor,
      dapoxetine was used to test its ability to ameliorate the pathological changes in
      the rat prostate. A dose response curve was constructed between the dose of
      dapoxetine and prostate weight as well as relative prostate weight, then a 5mg/kg
      dose was used as a representative dose for dapoxetine administration. Rats were
      divided into four groups; the control group that received the vehicle; the BPH
      induced group received daily s.c injection of 3mg/kg testosterone propionate
      dissolved in olive oil for four weeks; BPH-induced group treated with finasteride
      5mg/kg/day p.o and BPH-induced group treated with dapoxetine 5mg/kg/day p.o.
      Injection of testosterone increased prostate weight and relative prostate weight
      which were both returned back to the normal value after treatment with dapoxetine
      as well as finasteride. Testosterone also upregulated androgen receptor (AR) and
      proliferating cell nuclear antigen gene expression. Furthermore, testosterone
      injection elevated cyclooxygenase-II (COX II), inducible nitric oxide synthase
      (iNOS), B-cell lymphoma-2 (Bcl2) expression and tumor necrosis factor alpha
      content and reduced caspase-3 activity, Bcl-2-associated X protein (Bax)
      expression and Bax/Bcl2 ratio. Dapoxetine and finasteride administration reverted
      most of the changes made by testosterone injection. In conclusion, the current
      study provides an evidence for the protective effects of dapoxetine against
      testosterone-induced BPH in rats. This can be attributed, at least in part, to
      decreasing AR expression, and the anti-proliferative, anti-inflammatory and pro
      apoptotic activities of dapoxetine in BPH.

PMID- 27687056
TI  - Training in surgery of the temporomandibular joint: the UK trainers' perspective.
AB  - Surgery of the temporomandibular joint (TMJ) is increasingly recognised as a
      subspecialist area of interest within our specialty and many procedures such as
      arthroscopy, arthroplasty, and replacement of the TMJ are becoming increasingly
      centralised and restricted to certain regions. We previously made a national
      survey of trainees and have sought to augment this with a survey of trainers to
      find out the nature of practice and patterns of referral nationally. We have also
      examined the consultants' expectations of competent final-year trainees. To do
      this we made an electronic survey of Fellows of the British Association of Oral
      and Maxillofacial Surgeons (BAOMS) and received 82 responses (26%). Many just
      provided simple treatments within their clinical practice, only 16 did
      arthroscopy, and 14 alloplastic joint replacements. From those who answered the
      question, only 10 would allow a competent final-year trainee to do an alloplastic
      joint replacement under supervision. Referrals for TMJ subspecialist care were
      predominantly made to the West Midlands, East Midlands, and North West, with 24
      respondents stating they would either refer open TMJ surgery centrally within or
      outside the region. Centralisation of services means that training opportunities
      in surgery of the TMJ are reduced, and restricted to only a few regions. Other
      models of training may need to be introduced such as simulation, "taster"
      sessions, and brief clinical attachments. For the budding subspecialist, however,
      a dedicated Fellowship may become essential to ensure adequate exposure before
      starting independent consultant practice.

PMID- 27687057
TI  - Relationship of Modic Changes, Disk Herniation Morphology, and Axial Location to
      Outcomes in Symptomatic Cervical Disk Herniation Patients Treated With High
      Velocity, Low-Amplitude Spinal Manipulation: A Prospective Study.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether cervical disk
      herniation (CDH) location, morphology, or Modic changes (MCs) are related to
      treatment outcomes. METHODS: Magnetic resonance imaging (MRI) and outcome data
      from 44 patients with CDH treated with spinal manipulative therapy were
      evaluated. MRI scans were assessed for CDH axial location, morphology, and MCs.
      Pain (0-10 for neck and arm) and Neck Disability Index (NDI) data were collected
      at baseline; 2 weeks; 1, 3, and 6 months; and 1 year. The Patient's Global
      Impression of Change data were collected at all time points and dichotomized into
      "improved," yes or no. Fischer's exact test compared the proportion improved with
      MRI abnormalities. Numerical rating scale and NDI scores were compared with MRI
      abnormalities at baseline and change scores at all time points using the t test
      or Mann-Whitney U test. RESULTS: Patients who were Modic positive had higher
      baseline NDI scores (P = .02); 77.8% of patients who were Modic positive and
      53.3% of patients who were Modic negative reported improvement at 2 weeks (P =
      .21). Fifty percent of Modic I and 83.3% of Modic II patients were improved at 2
      weeks (P = .07). At 3 months and 1 year, all patients with MCs were improved.
      Patients who were Modic positive had higher NRS and NDI change scores. Patients
      with central herniations were more likely to improve only at the 2-week time
      point (P = .022). CONCLUSIONS: Although patients who were Modic positive had
      higher baseline NDI scores, the proportion of these patients improved was higher
      for all time points up to 6 months. Patients with Modic I changes did worse than
      patients with Modic II changes at only 2 weeks.

PMID- 27687058
TI  - Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung
      Cancer, but only in Squamous Cell Carcinoma Cases.
AB  - The aim of the study was to investigate the correlation between claudin (CLDN)
      protein expression and clinicopathological parameters as well as survival in
      histological subtypes of non-small cell lung cancer. Archived surgical resection
      specimens of 137 pathologic stage I primary bronchial cancers including 49
      adenocarcinomas of non-lepidic variants (ADC), 46 adenocarcinomas of lepidic
      variants (L-ADC), and 42 squamous cell carcinomas (SCC) were examined.
      Immunohistochemistry (IHC) using antibodies against CLDN1,-2,-3,-4,-7 proteins as
      well as semiquantitative estimation (IHC scores 0-5) were performed. Claudin IHC
      scores of L-ADC differed significantly from ADC (CLDN1: p = 0.009, CLDN2: p =
      0.005, CLDN3: p = 0.004, CLDN4: p = 0.001, CLDN7: p < 0.001, respectively) and
      SCC (CLDN1: p < 0.001, CLDN3: p < 0.001, CLDN7: p < 0.001, respectively). Highly
      significant CLDN3-CLDN4 parallel expression could be demonstrated in ADC and L
      ADC (p < 0.001 in both), which was not observed in SCC (p = 0.131). ADC and SCC
      showed no correlation with smoking, whereas in case of L-ADC heavier smoking
      correlated with higher CLDN3 expression (p = 0.020). Regarding claudin expression
      and survival, in SCC significant correlation could be demonstrated between CLDN1
      IHC positivity and better survival (p = 0.038). In NSCLC as a whole, high CLDN2
      expression proved to be a better prognostic factor when compared with cases where
      CLDN2 IHC score was 0-1 vs. 2-5 (p = 0.009), however, when analyzed separately,
      none of the histological subgroups showed correlation between CLDN2 expression
      and overall survival. The claudin expression pattern was significantly different
      not only between the SCC-ADC and SCC-L-ADC but also between the L-ADC and ADC
      histological subgroups, which strongly underlines that L-ADC represents a
      distinct entity within the ADC group. CLDN1 overexpression is a good prognostic
      factor in NSCLC, but only in the SCC subgroup.

PMID- 27687059
TI  - Anesthesia and analgesia methods for outpatient anterior cruciate ligament
      reconstruction.
AB  - INTRODUCTION: More and more anterior cruciate ligament (ACL) reconstructions are
      being performed as outpatient surgery in France, because of economic
      considerations. Postoperative pain is the most common reason for delayed
      discharge that could require hospitalization, and the main reason for
      unanticipated hospital admission. The purpose of this study was to define the
      best anesthesia and analgesia methods for ACL reconstruction. MATERIALS AND
      METHODS: This was a prospective, multicenter, comparative study performed between
      January 2014 and April 2015. Inclusion criteria were ACL reconstruction in
      patients above 15 years of age performed as an outpatient surgical procedure. The
      anesthesia techniques analyzed were general anesthesia, spinal anesthesia and
      quadruple nerve blockade. The analgesic methods studied were single-shot nerve
      blocks, continuous nerve blocks, peri-articular and intra-articular local
      infiltration analgesia (LIA), non-steroidal anti-inflammatory agents (NSAIDs) and
      intravenous corticosteroids. The main outcome criterion was pain on a visual
      analog scale (VAS). The secondary outcome criteria were delayed discharge of a
      patient who had undergone outpatient surgery, consumption of opioids and
      complications for the various anesthesia techniques and analgesia methods.
      RESULTS: In all, 680 patients were included in this study, which was 63% of the
      ACL reconstruction procedures performed during this period. The study population
      was 69% male and 31% female, with an average age of 30 years. Twenty-three
      patients (3.4%) could not be discharged on the day of surgery. No correlation was
      found with the anesthesia technique used. NSAID treatment was protective relative
      to delayed discharge (P=0.009), while opioid consumption was a risk factor
      (P<0.01). There were no differences in the pain levels related to the type of
      anesthesia. Peri-articular LIA of the hamstring tendon harvest site was
      effective. Intra-articular LIA did not provide better analgesia. Continuous nerve
      block had complication rates above 13%. DISCUSSION: All types of anesthesia were
      compatible with outpatient ACL reconstruction. No gold standard analgesia method
      can be defined based on this study's findings. However, we recommend multimodal
      analgesia associating peri-articular LIA or one-shot sensory saphenous nerve
      block, NSAIDs and corticosteroid treatment, and cryotherapy. LEVEL OF EVIDENCE:
      II, prospective comparative non-randomized study.

PMID- 27687060
TI  - Complications in posteromedial arthroscopic suture of the medial meniscus.
AB  - INTRODUCTION: All-inside posteromedial suture for lesions of the posterior horn
      of the medial meniscus in anterior cruciate ligament (ACL) repair provides
      effective freshening and good healing. HYPOTHESIS: The posteromedial portal
      provides satisfactory healing rates without increasing morbidity or complications
      rates. MATERIAL AND METHODS: Intra- and postoperative complications were
      collected for a consecutive single-center series of 132 patients undergoing
      posteromedial hook suture of the medial meniscus in ACL repair. Meniscal healing
      was assessed as the rate of recurrence of symptomatic medial meniscus lesions
      (Barret criteria) and on revision surgery, if any, in terms of the aspect and
      extent of the iterative lesion. The severity of any sensory disorder was assessed
      by questionnaire. RESULTS: The intraoperative complications rate was 1.5% (2
      saphenous vein punctures). At a mean 31months (range, 28-35months), there was no
      loss to follow-up. Twelve patients (9%) showed symptomatic recurrence of the
      medial meniscus lesion, requiring 10 repeat surgeries. In 6 cases (4.5%), the
      iterative lesion involved a smaller, more central part of the meniscus anterior
      to the sutures, of "postage-stamp" effect, possibly implicating the suture hook
      and/or non-absorbable sutures. There were no cases of infection or fistula.
      Postoperative hematoma occurred in 7% of patients. In total, 1.8% reported
      dysesthesia areas equal to or greater than the size of a credit card (45cm2).
      DISCUSSION: Some retears, or "partial failures", may implicate a new lesion
      caused by the suture hook and possibly prolonged by non-resorbable sutures.
      Hematoma and sensory disorder rates were comparable to those reported in isolated
      ACL repair without posteromedial portal. CONCLUSION: The present results show
      that posteromedial arthroscopic hook suture in posterior medial meniscus tear
      provides good healing rates without increased morbidity due to the supplementary
      portal. LEVEL OF EVIDENCE: IV.

PMID- 27687061
TI  - Pain after out-patient vs. in-patient ACL reconstruction: French prospective
      study of 1076 patients.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) repair is increasingly performed on
      an out-patient basis. In France, however, concern about post-operative pain
      remains a strong barrier to out-patient ACL repair. The primary objective of this
      study was to compare post-operative pain after ACL repair as out-patient versus
      in-patient surgery. The secondary objectives were to assess the time-course of
      post-operative pain and to identify factors associated with pain intensity.
      MATERIAL AND METHODS: A multicentre, prospective, comparative, non-randomised
      study was conducted in France for the French Society for Arthroscopy (SFA)
      symposium. Patients who underwent primary ACL repair between January 2014 and
      March 2015 were included if they were eligible for out-patient surgery. The
      choice between out-patient and in-patient surgery was based on organisational and
      logistical considerations. Pain intensity was self-evaluated by the patients
      using a visual analogue scale (VAS), pre-operatively then in the evening after
      surgery, during the night after surgery, and 1, 3, and 5 days after surgery. The
      patients performed the evaluations at home using websurvey.fr(r) software.
      Demographic data, the characteristics of the surgical procedure, and the IKDC and
      Lysholm scores before and after surgery were collected. RESULTS: Of the 1076
      patients included in the study, 680 had out-patient surgery and 396 in-patient
      surgery. Mean age was 30+/-9 years. The two groups were comparable at baseline.
      Pain intensity was not significantly different between the two groups at any of
      the measurement time points. Pain intensity showed a peak on post-operative day 1
      that was similar in the two groups. The initial post-operative pain intensity
      score predicted subsequent pain intensity: patients with VAS scores <2 on the day
      of surgery also had low pain scores after surgery. In both groups, factors
      associated with greater pain intensity were age <25 years, high pre-operative
      pain score, and surgery performed after noon. Neither surgical technique nor
      concomitant lesions and methods used to treat them were associated with pain
      intensity. Risk factors for severe post-operative pain (VAS score >7) in the out
      patient group were younger age, female gender, pre-operative VAS score >3, and
      tourniquet time >50minutes. CONCLUSION: Pain intensity is similar after out
      patient and in-patient ACL repair. Concern about pain should not be a barrier to
      performing ACL repair on an out-patient basis. Our data on the time-course of the
      pain and factors associated with greater pain intensity should prove useful for
      improving patient management after ACL repair. LEVEL OF EVIDENCE: Level III, case
      control study.

PMID- 27687062
TI  - French prospective multicenter comparative assessment of ambulatory surgery
      feasibility in anterior cruciate ligament reconstruction.
AB  - INTRODUCTION: The main objective of this multicenter study was to assess the
      feasibility of ambulatory surgery in France in anterior cruciate ligament (ACL)
      reconstructions for any technique or graft used (hamstring, patellar tendon,
      fascia lata). We hypothesized that a dedicated organization would guarantee the
      patient's safety. PATIENTS AND METHODS: A multicenter, non-randomized,
      prospective, comparative study, conducted within the SFA symposium was conducted
      between January 2014 and March 2015, included all the patients operated on for
      arthroscopic ACL reconstruction using different surgical techniques. The
      outpatient group (OP) included patients eligible for day surgery who provided
      informed consent; the conventional hospitalization group (CH) comprised patients
      declined for outpatient surgery for organizational reasons. The main outcome was
      failure of the admission mode defined by hospitalization of a patient undergoing
      outpatient surgery or rehospitalization within the 1st week after discharge. The
      secondary outcomes were assessment of pain and postoperative complications. A
      total of 1076 patients were studied with 680 in the OP group and 396 in the CH
      group. The mean age was 30years+/-9years. In the CH group, the mean hospital stay
      was 2.7+/-0.8days. RESULTS: Twenty-three OP patients were hospitalized or
      rehospitalized (3.4%). Thirty-six (5.2%) early postoperative complications were
      noted in the OP group and 17 (4.3%) in the CH group (non-significant difference).
      Mean postoperative pain on D0-D4 and satisfaction were comparable between the two
      groups. CONCLUSION: This prospective multicenter study observed no serious
      incidents. In a selected population, the risks are comparable to those of
      conventional hospitalization. Outpatient ACL surgery is therefore feasible in
      France in 2016. LEVEL OF PROOF: III: case-control study.

PMID- 27687063
TI  - Arthroscopic subtalar arthrodesis.
AB  - Arthroscopic subtalar arthrodesis is gaining in popularity based on evidence of
      bone fusion in over 90% of cases, with a shorter time to healing, a simpler
      postoperative course, and fewer complication compared to open surgery. Two
      arthroscopic techniques have been reported: one with the patient in lateral
      decubitus and lateral portals and the other with the patient prone and posterior
      portals. The objective of this technical note is to describe these two
      techniques, with emphasis on the specific characteristics of each.

PMID- 27687064
TI  - Functional outcomes after open versus arthroscopic Latarjet procedure: A
      prospective comparative study.
AB  - INTRODUCTION: The Latarjet procedure provides effective stabilization of
      chronically unstable shoulders. Since this procedure is mainly performed in a
      young athletic population, the functional impact is significant. Published data
      does not shed light on the time needed to recover work-related or sports-related
      function. Performing this procedure arthroscopically may improve functional
      recovery. This led us to carry out a prospective, multicenter study to compare
      the functional recovery after arthroscopic versus open Latarjet procedure.
      MATERIAL AND METHODS: Between June and November 2014, 184 patients were included
      in a prospective multicenter study: 85 in the open group and 99 in the
      arthroscopy group. The patients were evaluated preoperatively with the WOSI
      score. The early postoperative pain was evaluated on D3, D7 and D30. The WOSI
      score was determined postoperatively at 1, 3, 6 and 12 months of follow-up.
      RESULTS: The functional scores of the shoulder in both cohorts were identical
      overall preoperatively. In the immediate postoperative period, the arthroscopy
      group had statistically lower pain levels on D3 and D7. The postoperative WOSI
      was improved in both groups at 3 months, then continued to improve until it
      reached a plateau at 1 year. The WOSI score was better in the arthroscopy group
      at 3 months, but better in the open group at 6 months. CONCLUSION: This study
      found that a Latarjet procedure performed arthroscopically generates less
      immediately postoperative pain than when it is performed as an open procedure.
      The Latarjet procedure (whether open or arthroscopic) improves shoulder function,
      with normal function returning after 1 year.

PMID- 27687065
TI  - Anatomical and morphological study of the subcoracoacromial canal.
AB  - INTRODUCTION: Many clinical anatomy studies have looked into how variations in
      the acromion, coracoacromial ligament (CAL) and subacromial space are associated
      with rotator cuff injuries. However, no study up to now had defined anatomically
      the fibro-osseous canal that confines the supraspinatus muscle in the
      subcoracoacromial space. Through an anatomical study of the scapula, we defined
      the bone-related parameters of this canal and its anatomical variations.
      MATERIALS AND METHODS: This study on dry bones involved 71 scapulas. With
      standardised photographs in two orthogonal views (superior and lateral), the
      surface area of the subcoracoacromial canal and the anatomical parameters making
      up this canal were defined and measured using image analysis software. The
      primary analysis evaluated the anatomical parameters of the canal as a function
      of three canal surface area groups; the secondary analysis looked into how
      variations in the canal surface area were related to the type of acromion
      according to the Bigliani classification. RESULTS: Relative to glenoid width, the
      group with a large canal surface area (L) had significantly less lateral overhang
      of the acromion than the group with a small canal surface area (S), with ratios
      of 0.41+/-0.23 and 0.58+/-0.3, respectively (P=0.04). The mean length of the CAL
      was 46+/-8mm in the L group and 39+/-9mm in the S group (P=0.003). The
      coracoacromial arch angle was 38 degrees +/-11 degrees  in the L group and 34
      degrees +/-9 degrees  in the S group; the canal surface area was smaller in
      specimens with a smaller coracoacromial arch angle (P=0.20). CONCLUSION: Apart
      from acromial morphology, there could be innate anatomical features of the
      scapula that predispose people to extrinsic lesions to the supraspinatus tendon
      (lateral overhang, coracoacromial arch angle) by reducing the subcoracoacromial
      canal's surface area. LEVEL OF EVIDENCE: Anatomical descriptive study.

PMID- 27687066
TI  - Four novel polymorphisms of buffalo INSIG2 gene are associated with milk
      production traits in Chinese buffaloes.
AB  - Insulin-induced genes (INSIGs), including INSIG1 and INSIG2, are important
      mediators that play a pivotal role in the lipid metabolism and could cause the
      retention of the SCAP/SREBP complex. Therefore, the objective of this study is to
      detect the single nucleotide polymorphisms (SNPs) of buffalo INSIG2 gene and
      evaluate their associations with milk production traits in Chinese buffaloes. A
      total of four SNPs (g.621272A > G, g.621364A > C, g.632543G > A, and g.632684C >
      T) were identified using DNA pooled sequencing, and the SNP genotyping for the
      identified SNPs was performed by using Matrix-assisted laser
      desorption/ionization time of flight mass spectrometry method from 264
      individuals. The results showed that four SNPs were significantly associated with
      305-day milk yield or protein percentage in Murrah and crossbred breeds (P <
      0.05), but they had no significant effect on milk production traits in Nili-Ravi
      buffaloes (P > 0.05). Linkage disequilibrium (LD) analysis revealed that one
      haplotype block was successfully constructed, of which the diplotype H1H1 showed
      significant association with 305-day milk yield in Murrah buffaloes (P < 0.05).
      Our findings provide evidence that polymorphisms in buffalo INSIG2 gene are
      associated with milk production traits, and could be used as a candidate gene for
      marker-assisted selection in buffalo breeding program.

PMID- 27687068
TI  - Future of the Palliative Care Workforce: Preview to an Impending Crisis.

PMID- 27687067
TI  - Prosthesis-Patient Mismatch After Aortic Valve Replacement.
AB  - OPINION STATEMENT: Prosthesis-patient mismatch (PPM) occurs when the effective
      orifice area (EOA) of a normally functioning prosthesis is too small in relation
      to the patient's body size, resulting in abnormally high postoperative gradients.
      PPM is frequent following aortic valve replacement (AVR), and it is associated
      with increased risk of morbidity and mortality proportionally to its severity.
      Differential diagnosis between PPM and prosthetic valve stenosis is made by
      comparing the measured valve effective orifice area, by assessing the changes in
      valve area and gradient during follow-up and by evaluating leaflet morphology and
      mobility. Preventive strategies to avoid or minimize PPM should be implemented
      especially in the patients who are at high risk for severe PPM and in those who
      have vulnerability factors to PPM. Transcatheter AVR may be superior to surgical
      AVR for the prevention of PPM and associated adverse cardiac events, particularly
      in the subset of patients with a small (<21 mm) aortic annulus. In this article,
      we discuss the most updated data regarding the diagnosis, clinical impact, and
      prevention of PPM after AVR.

PMID- 27687069
TI  - Intravascular Large B Cell Lymphoma Presenting as Transient Erythema Nodosum-Like
      Lesions and Fever.

PMID- 27687070
TI  - Radiation-Induced Cardiac Valve Disease.

PMID- 27687071
TI  - Bataclan's Ulnar Nerve Syndrome.

PMID- 27687072
TI  - Author's response to 'Valsalva manoeuvre using a syringe: physics and
      implications'.

PMID- 27687073
TI  - Valsalva manoeuvre using a syringe: physics and implications.

PMID- 27687074
TI  - Carbapenemase-producing Enterobacteriaceae in the UK: a national study (EuSCAPE
      UK) on prevalence, incidence, laboratory detection methods and infection control
      measures.
AB  - OBJECTIVES: To estimate UK prevalence and incidence of clinically significant
      carbapenemase-producing Enterobacteriaceae (CPE), and to determine
      epidemiological characteristics, laboratory methods and infection prevention and
      control (IPC) measures in acute care facilities. METHODS: A 6 month survey was
      undertaken in November 2013-April 2014 in 21 sentinel UK laboratories as part of
      the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE)
      project. Up to 10 consecutive, non-duplicate, clinically significant and
      carbapenem-non-susceptible isolates of Escherichia coli or Klebsiella pneumoniae
      were submitted to a reference laboratory. Participants answered a questionnaire
      on relevant laboratory methods and IPC measures. RESULTS: Of 102 isolates
      submitted, 89 (87%) were non-susceptible to >=1 carbapenem, and 32 (36%) were
      confirmed as CPE. CPE were resistant to most antibiotics, except colistin (94%
      susceptible), gentamicin (63%), tigecycline (56%) and amikacin (53%). The
      prevalence of CPE was 0.02% (95% CI = 0.01%-0.03%). The incidence of CPE was
      0.007 per 1000 patient-days (95% CI = 0.005-0.010), with north-west England the
      most affected region at 0.033 per 1000 patient-days (95% CI = 0.012-0.072).
      Recommended IPC measures were not universally followed, notably screening high
      risk patients on admission (applied by 86%), using a CPE 'flag' on patients'
      records (70%) and alerting neighbouring hospitals when transferring affected
      patients (only 30%). Most sites (86%) had a laboratory protocol for CPE
      screening, most frequently using chromogenic agar (52%) or MacConkey/CLED agars
      with carbapenem discs (38%). CONCLUSIONS: The UK prevalence and incidence of
      clinically significant CPE is currently low, but these MDR bacteria affect most
      UK regions. Improved IPC measures, vigilance and monitoring are required.

PMID- 27687075
TI  - Active follow-up versus passive linkage with cancer registries for case
      ascertainment in a cohort.
AB  - BACKGROUND: Ascertaining incident cancers is a critical component of cancer
      focused epidemiologic cohorts and of cancer prevention trials. Potential methods:
      for cancer case ascertainment include active follow-up and passive linkage with
      state cancer registries. Here we compare the two approaches in a large cancer
      screening trial. METHODS: The Prostate, Lung, Colorectal and Ovarian (PLCO)
      cancer screening trial enrolled 154,955 subjects at ten U.S. centers and followed
      them for all-cancer incidence. Cancers were ascertained by an active follow-up
      process involving annual questionnaires, retrieval of records and medical record
      abstracting to ascertain and confirm cancers. For a subset of centers, linkage
      with state cancer registries was also performed. We assessed the agreement of the
      two methods in ascertaining incident cancers from 1993 to 2009 in 80,083 subjects
      from six PLCO centers where cancers were ascertained both by active follow-up and
      through linkages with 14 state registries. RESULTS: The ratio (times 100) of
      confirmed cases ascertained by registry linkage compared to active follow-up was
      96.4 (95% CI: 95.1-98.2). Of cancers ascertained by either method, 86.6% and
      83.5% were identified by active follow-up and by registry linkage, respectively.
      Of cancers missed by active follow-up, 30% were after subjects were lost to
      follow-up and 16% were reported but could not be confirmed. Of cancers missed by
      the registries, 27% were not sent to the state registry of the subject's current
      address at the time of linkage. CONCLUSION: Linkage with state registries
      identified a similar number of cancers as active follow-up and can be a cost
      effective method to ascertain incident cancers in a large cohort.

PMID- 27687076
TI  - Self-reported illness among Boston-area international travelers: A prospective
      study.
AB  - BACKGROUND: The Boston Area Travel Medicine Network surveyed travelers on travel
      related health problems. METHODS: Travelers were recruited 2009-2011 during pre
      travel consultation at three clinics. The investigation included pre-travel data,
      weekly during-travel diaries, and a post-travel questionnaire. We analyzed
      demographics, trip characteristics, health problems experienced, and assessed the
      relationship between influenza vaccination, influenza prevention advice, and
      respiratory symptoms. RESULTS: Of 987 enrolled travelers, 628 (64%) completed all
      surveys, of which 400 (64%) reported health problems during and/or after travel;
      median trip duration was 12 days. Diarrhea affected the most people during travel
      (172) while runny/stuffy nose affected the most people after travel (95). Of
      those with health problems during travel, 25% stopped or altered plans; 1% were
      hospitalized. After travel, 21% stopped planned activities, 23% sought physician
      or other health advice; one traveler was hospitalized. Travelers who received
      influenza vaccination and influenza prevention advice had lower rates of
      respiratory symptoms than those that received influenza prevention advice alone
      (18% vs 28%, P = 0.03). CONCLUSIONS: A large proportion of Boston-area travelers
      reported health problems despite pre-travel consultation, resulting in
      inconveniences. The combination of influenza prevention advice and influenza
      immunization was associated with fewer respiratory symptoms than those who
      received influenza prevention advice alone.

PMID- 27687077
TI  - A proposal for a test method for assessment of hazard property HP 12 ("Release of
      an acute toxic gas") in hazardous waste classification - Experience from 49
      waste.
AB  - A stepwise method for assessment of the HP 12 is proposed and tested with 49
      waste samples. The hazard property HP 12 is defined as "Release of an acute toxic
      gas": waste which releases acute toxic gases (Acute Tox. 1, 2 or 3) in contact
      with water or an acid. When a waste contains a substance assigned to one of the
      following supplemental hazards EUH029, EUH031 and EUH032, it shall be classified
      as hazardous by HP 12 according to test methods or guidelines (EC, 2014a, 2014b).
      When the substances with the cited hazard statement codes react with water or an
      acid, they can release HCl, Cl2, HF, HCN, PH3, H2S, SO2 (and two other gases very
      unlikely to be emitted, hydrazoic acid HN3 and selenium oxide SeO2 - a solid with
      low vapor pressure). Hence, a method is proposed:For a set of 49 waste, water
      addition did not produce gas. Nearly all the solid waste produced a gas in
      contact with hydrochloric acid in 5 min in an automated calcimeter with a volume
      >0.1L of gas per kg of waste. Since a plateau of pressure is reached only for
      half of the samples in 5 min, 6 h trial with calorimetric bombs or glass flasks
      were done and confirmed the results. Identification of the gases by portable
      probes showed that most of the tested samples emit mainly CO2. Toxic gases are
      emitted by four waste: metallic dust from the aluminum industry (CO), two air
      pollution control residue of industrial waste incinerator (H2S) and a halogenated
      solvent (organic volatile(s) compound(s)). HF has not been measured in these
      trials started before the present definition of HP 12. According to the
      definition of HP 12, only the H2S emission of substances with hazard statement
      EUH031 is accounted for. In view of the calcium content of the two air pollution
      control residue, the presence of calcium sulphide (EUH031) can be assumed. These
      two waste are therefore classified potentially hazardous for HP 12, from a total
      of 49 waste. They are also classified as hazardous for other properties (HP 7,
      10and14 for one of them, and HP 10and14 for the other one respectively). Given
      these results, it can be assumed that few common household and industrial waste
      will be classified hazardous only by HP 12.

PMID- 27687078
TI  - Where next on e-waste in Australia?
AB  - For almost two decades waste electrical and electronic equipment, WEEE or e
      waste, has been considered a growing problem that has global consequences. The
      value of recovered materials, primarily in precious and base metals, has prompted
      some parts of the world to informally and inappropriately process e-waste causing
      serious environmental and human health issues. Efforts in tackling this issue
      have been limited and in many ways unsuccessful. The global rates for formal e
      waste treatment are estimated to be below the 20% mark, with the majority of end
      of-life (EoL) electronic devices still ending up in the landfills or processed
      through rudimentary means. Industrial confidentiality regarding device
      composition combined with insufficient reporting requirements has made the task
      of simply characterizing the problem difficult at a global scale. To address some
      of these key issues, this paper presents a critical overview of existing
      statistics and estimations for e-waste in an Australia context, including
      potential value and environmental risks associated with metals recovery. From our
      findings, in 2014, on average per person, Australians purchased 35kg of
      electrical and electronic equipment (EEE) while disposed of 25kg of WEEE, and
      possessed approximately 320kg of EEE. The total amount of WEEE was estimated at
      587kt worth about US$ 370million if all major metals are fully recovered. These
      results are presented over the period 2010-2014, detailed for major EEE product
      categories and metals, and followed by 2015-2024 forecast. Our future projection,
      with the base scenario fixing EEE sales at 35kg per capita, predicts
      stabilization of e-waste generation in Australia at 28-29kg per capita, with the
      total amount continuing to grow along with the population growth.

PMID- 27687079
TI  - Perceptions of Gown and Glove Use to Prevent Methicillin-resistant Staphylococcus
      aureus Transmission in Nursing Homes.
AB  - OBJECTIVES: To explore current use and perceptions of glove and gown use in
      nursing homes. DESIGN: Qualitative study using focus groups and semi-structured
      interviews. SETTING: Three community-based nursing homes in Maryland.
      PARTICIPANTS: Direct care staff, administrators, and residents. METHODS: We
      conducted three focus groups among nursing home staff, one focus group among
      nursing home administrators, and five interviews with residents. Topic guides
      were created based on our recent study results and a review of the literature.
      Two investigators separately analyzed the transcribed recordings and identified
      recurrent themes. RESULTS: Direct care staff reported using gowns and gloves
      primarily as self-protection against contact with bodily fluids, not to prevent
      MRSA transmission. Glove use was described as common and more acceptable to staff
      and residents than gown use. Administrators were surprised that MRSA transmission
      to health care worker hands and clothing occurred during activities when direct
      care staff perceives no contact with bodily fluids. Staff and administrators
      expressed willingness to use gowns and gloves for high-risk care activities,
      particularly if use is targeted toward specific types of residents such as those
      with pressure ulcers. There was a knowledge deficit about MRSA transmission and
      infection among direct care staff and residents. CONCLUSIONS: Results from this
      study will inform a strategy to reduce MRSA transmission in long-term care.

PMID- 27687080
TI  - Natural selection? The evolution of diagnostic criteria for gestational diabetes.
AB  - Gestational diabetes is a common pregnancy disorder which is generally managed
      with diet, exercise, metformin or insulin treatment and which usually resolves
      after delivery of the infant. Identifying and treating gestational diabetes
      improves maternal and fetal outcomes and allows for health promotion to reduce
      the mother's risk of type 2 diabetes in later life. However, there remains
      considerable controversy about the optimal method of identification and diagnosis
      of women with gestational diabetes. The NICE-2015 diagnostic criteria (75 g oral
      glucose tolerance test (OGTT) 0 h >=5.6 mmol/L; 2 h >=7.8 mmol/L) are based upon
      cost-effectiveness estimates using observational data, while the WHO-2013
      criteria (75 g OGTT 0 h >=5.1 mmol/L; 1 h >=10.0 mmol/L; 2 h >=8.5 mmol/L)
      identify women and infants at risk of adverse outcomes according to prospective
      data. There is also considerable controversy about testing for gestational
      diabetes using universal or risk factor-based screening, and when and how testing
      should be performed. The aim of this review is to provide a summary of the
      clinical biochemistry aspects to these debates and to highlight the importance of
      appropriate identification of gestational diabetes and subsequent type 2 diabetes
      in this population.

PMID- 27687083
TI  - Evaluation of a reduced centrifugation time and higher centrifugal force on
      various general chemistry and immunochemistry analytes in plasma and serum.
AB  - Background Centrifugation of blood samples is an essential preanalytical step in
      the clinical biochemistry laboratory. Centrifugation settings are often altered
      to optimize sample flow and turnaround time. Few studies have addressed the
      effect of altering centrifugation settings on analytical quality, and almost all
      studies have been done using collection tubes with gel separator. Methods In this
      study, we compared a centrifugation time of 5 min at 3000 *  g to a standard
      protocol of 10 min at 2200 *  g. Nine selected general chemistry and
      immunochemistry analytes and interference indices were studied in lithium heparin
      plasma tubes and serum tubes without gel separator. Results were evaluated using
      mean bias, difference plots and coefficient of variation, compared with maximum
      allowable bias and coefficient of variation used in laboratory routine quality
      control. Results For all analytes except lactate dehydrogenase, the results were
      within the predefined acceptance criteria, indicating that the analytical quality
      was not compromised. Lactate dehydrogenase showed higher values after
      centrifugation for 5 min at 3000 *  g, mean bias was 6.3 +/- 2.2% and the
      coefficient of variation was 5%. Conclusions We found that a centrifugation
      protocol of 5 min at 3000 *  g can be used for the general chemistry and
      immunochemistry analytes studied, with the possible exception of lactate
      dehydrogenase, which requires further assessment.

PMID- 27687081
TI  - Falsely elevated serum oestradiol due to exemestane therapy.
AB  - In this study, we present a case of falsely elevated oestradiol (E2)
      concentration, determined by two immunoassays, in a breast cancer patient
      receiving exemestane therapy. The positive bias of immunochemical measurements
      was revealed using liquid chromatography tandem mass spectrometry which showed
      undetectable E2 concentration. The discrepancy is expected to be a consequence of
      the structural resemblance of E2 and exemestane sharing the same steroidal
      backbone. Inaccurate laboratory findings in therapy monitoring, as in this case,
      may lead to unnecessary changes of therapy.

PMID- 27687082
TI  - Elevated concentrations of hypoxia-inducible factor-1alpha in patients with
      fracture and concomitant traumatic brain injury.
AB  - Background Compelling evidence indicate that traumatic brain injury is highly
      related to accelerated bone fracture repair, but the underlying mechanism still
      remains elusive. Fracture repair process relies greatly on the formation of new
      blood vessels in fracture site, and angiogenic factors have been confirmed to be
      essential for the initiation and maintenance of the fracture healing. Hypoxia
      inducible factor-1alpha was demonstrated to be a critical regulator of angiogenic
      osteogenic coupling during bone development and regeneration. The aim of the
      present study was to investigate the local and circulating concentrations of
      hypoxia-inducible factor-1alpha in patients with long-bone fractures and
      concomitant traumatic brain injury and to determine the potential role of hypoxia
      inducible factor-1alpha in fracture healing. Methods Twenty-five patients with a
      long-bone fracture and concomitant traumatic brain injury (FT group) and 33
      without a brain injury (Fr group) were enrolled in this study. Healthy subjects
      donated serum samples as control. Serum samples were collected over a period of
      six months, following a standardized time schedule. Hypoxia-inducible factor
      1alpha concentrations were measured in fracture haematoma and serum of patients
      in both groups using enzyme-linked immunosorbent assay. Results Patients in FT
      group had a short time to union. Serum hypoxia-inducible factor-1alpha
      concentrations elevated in the early healing period and reached the maximum level
      during intramembranous bone formation phase in both groups. Thereafter, it
      decreased continuously and approached to the minimum levels until the end of the
      observation period. Serum hypoxia-inducible factor-1alpha concentrations in both
      groups were significantly higher compared with controls and hypoxia-inducible
      factor-1alpha concentrations in both serum and fracture haematoma were higher in
      FT group than that in Fr group. Fracture haematoma contained significantly higher
      hypoxia-inducible factor-1alpha concentrations compared with hypoxia-inducible
      factor-1alpha concentrations in serum. Serum hypoxia-inducible factor-1alpha
      concentrations had a positive correlation with hypoxia-inducible factor-1alpha
      concentrations in fracture haematoma in patients with fractures. Conclusions
      These findings suggest the local and systemic involvement of hypoxia-inducible
      factor-1alpha in fracture healing and the accelerated fracture repair in patients
      with traumatic brain injury might be associated with elevated hypoxia-inducible
      factor-1alpha concentrations in fracture haematoma and serum.

PMID- 27687084
TI  - Assessment of a semi-quantitative screening method for diagnosis of ethylene
      glycol poisoning.
AB  - Background Ethylene glycol poisoning remains a rare but important presentation to
      acute toxicology units. Guidelines recommended that ethylene glycol should be
      available as an 'urgent' test within 4 h, but these are difficult to deliver in
      practice. This study assessed a semi-quantitative enzymatic spectrophotometric
      assay for ethylene glycol compatible with automated platforms. Methods The
      ethylene glycol method was assessed in 21 samples from patients with an increased
      anion gap and metabolic acidosis not due to ethylene glycol ingestion, and seven
      samples known to contain ethylene glycol. All samples were analysed in random
      order in a blinded manner to their origin on a laboratory spectrophotometer.
      Results In this study, seven samples were known to contain ethylene glycol at
      concentrations >100 mg/L. The method correctly identified all seven samples as
      containing ethylene glycol. No false-positives were observed. Thirteen samples
      gave clear negative results. Ethylene glycol was present at <20 mg/L in one
      sample, but this sample remained within the limits of the negative control.
      Passing-Bablock correlation of estimates of ethylene glycol concentration against
      results obtained when the samples had been analysed using the quantitative method
      on an automated analyser showed a good correlation (R = 0.84) but with an
      apparent under-recovery. Conclusions A semi-quantitative assay for ethylene
      glycol was able to discriminate well between samples containing ethylene glycol
      and those with other causes of acidosis. It is a practical small-scale assay for
      rapid identification of cases of ethylene glycol poisoning.

PMID- 27687085
TI  - Risk factors for recurrent injurious falls that require hospitalization for older
      adults with dementia: a population based study.
AB  - BACKGROUND: Older adults with dementia are at an increased risk of falls,
      however, little is known about risk factors for recurrent injurious falls (a
      subsequent fall after the first fall has occurred) among this group. This study
      aimed to identify risk factors for recurrent injurious falls requiring
      hospitalization among adults aged 60+ years with dementia. METHODS: This
      retrospective, whole-population cohort study was conducted using the Western
      Australian Hospital Morbidity Data System and Western Australian Death
      Registrations from 2001 to 2013. Survival analysis using a stratified conditional
      Cox model (type 1) was undertaken to identify risk factors for recurrent
      injurious falls requiring hospitalization. RESULTS: There were 32,519
      participants with an index hospital admission with dementia during the study
      period. Over 27 % (n = 8970) of the cohort experienced a total of 11,073
      injurious falls requiring hospitalization during follow up with 7297 individuals
      experiencing a single fall, 1330 experiencing two falls and 343 experiencing
      three or more falls. The median follow-up time for each individual was 2.49
      years. Females were at a significantly increased risk of 7 % for recurrent
      injurious falls resulting in hospitalization (adjusted hazard ratio 1.07, 95 % CI
      1.01-1.12), compared to males. Increasing age, living in rural areas, and having
      an injurious fall in the year prior to the index hospital admission with dementia
      also increased the risk of recurrent injurious falls resulting in
      hospitalization. CONCLUSIONS: Screening those with dementia for injurious falls
      history could help to identify those most at risk of recurrent injurious falls.
      Improvement of heath care and falls prevention services for those with dementia
      who live in rural areas may also reduce recurrent injurious falls.

PMID- 27687086
TI  - Ships as future floating farm systems?
AB  - Environmental and agriculture challenges such as severe drought, desertification,
      sprawling cities and shrinking arable lands in large regions in the world compel
      us to think about alternative and sustainable farming systems. Ongoing projects
      to build floating cities in the sea suggest that building specific ships for
      farming purposes (as farming ships or farming boats) would also be attainable to
      introduce new farming surfaces and boost food production worldwide to cope with
      food insecurity issues.

PMID- 27687087
TI  - Nodal marginal zone lymphoma: mutation status analyses of CD79A, CD79B, and MYD88
      reveal no specific recurrent lesions.

PMID- 27687088
TI  - Possible role of chromatin alteration in the radiosensitivity of ataxia
      telangiectasia.
AB  - Cells derived from individuals with ataxia-telangiectasia (A-T) are known to
      exhibit increased sensitivity to ionizing radiation and certain radiomimetic
      chemical agents. Here we summarize our findings regarding the role of chromosome
      damage and repair in this radiosensitivity. Lymphoblas- toid cells derived from A
      T homozygotes were characterized for initial chromosome (premature chromosome
      condensation) and DNA (neutral filter elution) damage and repair kinetics in
      cells from G1 and G2 cell cycle phases. Despite initial levels of DNA damage
      being similar to normal controls, A-T cells exhibited nearly a two-fold higher
      initial amount of chromosome damage. Different A-T cell lines exhibited differing
      chromosome repair capacities compared with control lymphoblastoid cell lines.
      These results suggest that A-T cells have an altered chromatin structure whereby
      DNA double-strand breaks are apparently more efficiently converted into
      chromosome breaks. Four A-T heterozygote cell lines were examined for chromosome
      damage and repair in the same fashion and all exhibited increased levels of
      chromosome damage, although the degree of sensitivity was more prominent in G2
      phase cells (two-fold higher) than in G1 phase cells (1-5-fold higher than normal
      controls). These results suggest that A-T heterozygotes also exhibit an altered
      chromatin structure which impacts on chromosome damage expression. Of interest, A
      T cells also exhibited increased chromosome stickiness after irradiation, and
      telomere regions appeared to be frequently involved. While the molecular basis
      for preferential telomere involvement is not understood, these results again
      suggest that structural alterations in the chromatin of A-T cells may play an
      important role in A-T radiosensitivity.

PMID- 27687089
TI  - Enhanced chromosomal response of ataxia-telangiectasia cells to specific types of
      DNA double-strand breaks.
AB  - The chromosomal response of two ataxiatelangiectasia (A-T) lymphoblastoid cell
      lines (A-T-PA and A-T-KM) to restriction endonucleases (RE) is compared with that
      of a normal (N-SW) lymphoblastoid cell line. The RE used were PvuII (generating
      DNA double-strand breaks with blunt termini), BamHI (cohesive termini with 4
      base, 5' overhangs) and PstI (cohesive termini with 4 base 3' overhangs).
      Chromatid aberrations were analysed in cells 5 h after treatment. Cells were
      porated using streptolysin O to allow entry of RE. Both A-T lines showed an
      enhanced frequency of chromatid breaks in G2 phase compared with normal cells in
      response to RE. The enhanced response of A-T cells was most marked in the case of
      PvuII treatment when the enhancement ratios were 2-5 and 4-2 for A-T-PA and A-T
      KM respectively. However, the frequency of DNA double-strand breaks (dsb),
      measured by neutral filter elution, were considerably lower in A-T-PA cells than
      N-SW, due to a lower efficiency of poration. When A-T- PA cells were treated with
      streptolysin O at a higher concentration (0-3 Units/ml), a condition that
      apparently led to a similar level of poration in A-T-PA as in N-SW cells treated
      with 0-06 Units/ml as judged by the similar number of dsb induced in the two
      lines for a given PvuII concentration, the enhancement ratio for A-T-PA cells
      treated with PvuII increased from 2-5 to 5-8. BamHI and PstI were found to be
      less clastogenic in all three cell lines as found previously for Chinese hamster
      cells, although part of this effect may be due to a lower activity, particularly
      in the case of PstI. However, even at a 4-6-fold higher concentration, BamHI was
      still less clastogenic than PvuII. It is concluded that dsb with blunt termini
      are more clastogenic than those with cohesive termini. The results suggest that
      the chromosomal sensitivity of A-T cells may result from a defect causing a
      higher rate of conversion of dsb into chromatid aberrations.

PMID- 27687090
TI  - Cloning efficiency and spontaneous mutant frequency in circulating T-lymphocytes
      in ataxia-telangiectasia patients.
AB  - The mutant frequency at the hprt locus in circulating T-lymphocytes has been
      determined in 16 ataxia- telangiectasia (A-T) patients, 19 A-T heterozygotes and
      12 A-T sibs. Mutant frequency in the A-T patients is highly significantly
      elevated as a group, even when the relatively poor cloning efficiency of many of
      the A-T lymphocyte samples is taken into account. However, within the A-T set,
      considerable variation in both cloning efficiency and mutant frequency is seen.
      Cellular radiation sensitivity, measured by clonal survival assays and chromosome
      breakage, also varies, as do the clinical symptoms of the patients, including the
      age at which they become wheelchair bound and the severity of their
      telangiectasia. Here all the information available to us on this group of
      patients is presented in an attempt to discern if there is any relationship
      between those cellular characteristics we have observed and the severity of the
      symptoms and progression of the disease in the patients. Although we feel that it
      may be relevant that the adult patients in our study all have mutant frequencies
      that are not highly elevated, insufficient data are available at present to
      resolve any relationship between the heterogeneous clinical symptoms and cellular
      responses seen in the A-T patients as a group.

PMID- 27687091
TI  - The nature of ataxia-telangiectasia: problems and perspectives.

PMID- 27687092
TI  - Radiation checkpoints in model systems.
AB  - The response to DNA damaging agents includes a delay to progression through the
      cell cycle. Irradiation of premitotic cells causes a delay to mitosis and
      irradiation of Gi and S phase cells causes a delay to DNA synthesis. These delays
      have become known as checkpoints. The mechanisms that mediate the mitotic (or G2)
      checkpoint delay have recently come under study in yeast model systems. Work in
      the eukaryotic organisms S. cerevisiae and S. pombe has identified at least seven
      proteins controlling the interactions between DNA damage and cell cycle
      progression. Genetic analysis of this checkpoint pathway has identified
      substantial overlap with the feedback controls that co-ordinate progression
      through the cell cycle. Molecular analysis has revealed structural conservation
      between these highly diverged yeasts, which suggests that similar proteins may
      act in related pathways in mammalian cells. In addition, the rad24 and rad25
      genes of S. pombe (which are involved in the radiation checkpoint) encode
      functionally overlapping essential proteins that are highly conserved in
      mammalian cells. Studies of checkpoints in the yeasts may therefore help to
      define the signal pathways that control cell cycle delay in mammalian cells
      following irradiation, some of which have been proposed to be deficient in A-T
      cells.

PMID- 27687093
TI  - Testing the role of p53 in the expression of genetic instability and apoptosis in
      ataxia-telangiectasia.
AB  - We have obtained initial evidence supporting a new model for the human disease
      ataxia-telangiectasia (A-T), in which the A-T and p53 genes play crucial roles in
      a signal transduction network that activates multiple cellular functions in
      response to DNA damage. Three of the model's predictions were tested. (1)
      Disrupting cell cycle checkpoints should increase spontaneous rates in normal
      cells. In order to interfere with the G1/S checkpoint, we transfected a normal
      cell line with vectors expressing either a dominant-negative p53ala143 mutant or
      a human papilloma virus E6 gene. These transformants showed 10-80-fold elevations
      in spontaneous recombination rates when compared with their parent. (2) A-T cells
      should be sensitive to DNA damage-induced apoptosis. Widespread apoptosis was
      detectable in four A-T fibroblast lines, but not two control lines, beginning 24
      h after exposure to X-rays or streptonigrin, but not UV. Streptonigrin also
      induced widespread apoptosis in A-T lymphoblasts but not in control lymphoblasts.
      (3) Disruption of p53 function in A-T cells should increase their mutagen
      resistance by interfering with apoptosis. Stable transfection of either the
      p53143ala or the HPV18 E6 construct was associated with acquisition of
      streptonigrin and radiation resistance, while transfection with the p53143ala
      construct did not affect the streptonigrin sensitivity of a control cell line.

PMID- 27687094
TI  - Defect in radiation signal transduction in ataxia-telangiectasia.
AB  - Exposure of mammalian cells to ionizing radiation causes a delay in progression
      through the cycle at several checkpoints. Cells from patients with ataxia
      telangiectasia (A-T) ignore these checkpoint controls postirradiation. The tumour
      suppressor gene product p53 plays a key role at the G1/S checkpoint preventing
      the progression of cells into S phase. The induction of p53 by radiation is
      reduced and/or delayed in A-T cells, which appears to account for the failure of
      delay at the G1/S checkpoint. We have investigated further this defect in
      radiation signal transduction in A-T. While the p53 response was defective after
      radiation, agents that interfered with cell cycle progression such as mimosine,
      aphidicolin and deprivation of serum led to a normal p53 response in A-T cells.
      None of these agents caused breaks in DNA, as determined by pulse-field gel
      electrophoresis, in order to elicit the response. Since this pathway is mediated
      by protein kinases, we investigated the activity of several of these enzymes in
      control and A-T cells. Ca+2-dependent and -independent protein kinase C
      activities were increased by radiation to the same extent in the two cell types,
      a variety of serine/threonine protein kinase activities were approximately the
      same and anti-tyrosine anti-bodies failed to reveal any differences in protein
      phosphorylation between A-T and control cells. It is not evident what is the
      nature of the defect in signal transduction in A-T cells. However, it is clear
      that the p53 response is normal in these cells after exposure to some agents and
      it is mediated through protein kinase C or another serine/threonine kinase.

PMID- 27687095
TI  - Radiation-induced G2 delay and spontaneous chromosome aberrations in ataxia
      telangiectasia homozygotes and heterozygotes.
AB  - The extent of cell cycle delay of lymphocytes X-irradiated in G2 phase was
      measured by mitotic inhibition determinations in 66 controls, 14 ataxia
      telangiectasia (A-T) homozygotes and 27 obligate heterozygotes, Homozygotes had a
      significantly reduced mitotic index (MI) in unirradiated samples and showed
      significantly less radiation-induced mitotic inhibition than controls, This
      confirms our earlier disputed observations on A-T fibroblasts and demonstrates a
      G2 checkpoint defect in addition to the well-known defects in S phase and at the
      G1-S phase transition. There are two separate and opposite abnormal Ga responses
      of A-T cells; a primary event in which cells in G2 at the time of irradiation
      suffer less delay than controls, and a secondary event in which cells irradiated
      at earlier stages of the cycle are more delayed when they pass into G2, The MI of
      unirradiated heterozygote cells and the extent of mitotic inhibition were
      indistinguishable from controls. Spontaneous unstable chromosome aberrations
      were, as previously reported, significantly higher in homozygotes than in
      controls. This was true for breaks, but not for gaps, There was a suggestion of
      an increase in breaks in heterozygotes, but a much larger study would be required
      to confirm or refute this.

PMID- 27687096
TI  - Prenatal diagnosis of ataxia-telangiectasia and Nijmegen Breakage Syndrome by the
      assay of radioresistant DNA synthesis.
AB  - Prenatal diagnosis was performed in 16 pregnancies at risk of ataxia
      telangiectasia (A-T) or Nijmegen Breakage Syndrome (NBS). Radioresistant DNA
      synthesis (RDS) was investigated in cultured chorionic villus (CV) cells and/or
      amniotic fluid (AF) cells. In four pregnancies, an affected foetus was diagnosed
      with increased RDS in cultured CV cells. In three of the four cases confirmation
      of the diagnosis was obtained by analysis of AF cells and/or skin fibroblasts
      from the foetus cultured after termination of the pregnancy; in the fourth case a
      fibroblast culture from the aborted foetus failed. In one case, only AF cells
      could be analysed in a late stage of pregnancy; pregnancy was terminated due to
      intermediate/ equivocal results but the foetal fibroblasts showed normal RDS.
      Normal RDS was demonstrated in the other 11 pregnancies at 25% risk either by
      analysis of CV cells (nine cases) or of AF cells (two cases). In some cases the
      (normal) results on the CV cells were corroborated by subsequent analysis of AF
      cells. The results suggest that RDS analysis of CV cells allows reliable prenatal
      diagnosis of A-T/NBS. However, amniocentesis may be necessary to confirm normal
      results on CV cells if the foetus is female (because of the risk of maternal cell
      contamination) or in the rare case of equivocal results.

PMID- 27687097
TI  - Cancer risks in A-T heterozygotes.
AB  - It is well established that ataxia-telangiectasia (A-T) patients suffer a grossly
      elevated risk of cancer, particularly lymphoma and leukaemia, but the possibility
      of an excess cancer risk of cancer in heterozygotes carriers of A-T mutations is
      more controversial. A number of studies indicate that female relatives of A-T
      patients suffer excess risk of breast cancer; based on an overview of all
      currently available data the esti-mated relative risk of breast cancer to A-T
      heterozygotes is 3.9-fold (95%CI 2.1-7.2). There is some suggestion that relative
      risk declines with age. In contrast, there is no consistent evidence of a risk
      from any other cancer; the estimated risk from all studies is 1.9 (95%CI 1.5-2.5)
      but some studies show a larger effect whilst others show no excess risk. On the
      basis of these results and the likely frequency of the A-T gene, A-T
      heterozygotes would account for between 1 and 13% of breast cancer cases, with
      3.8% being the best estimate. However, unless the breast cancer risk has been
      seriously underestimated, the A-T gene will make little contribution to familial
      breast cancer.

PMID- 27687098
TI  - Nijmegen Breakage Syndrome: a progress report.
AB  - We report the findings in the first 30 patients with the Nijmegen Breakage
      Syndrome (NBS). All had microcephaly from birth, short stature and a 'bird-like'
      face. Most of them suffered from recurrent respiratory tract infections.
      Intelligence was normal in half of the patients. Serum immunoglobulins were
      disturbed in 22/25 patients investigated (IgG deficiency, IgA deficiency, IgG2
      and IgG4 deficiency) and T cell defects were found in 23/24 patients tested. The
      immunodeficiency appears to be more severe than in A-T. Chromosomal aberrations
      in cultured T lymphocytes occurred preferentially in chromosomes 7 and 14 and at
      the same breakpoints as in A-T. However, the percentage of chromosome 7 and/or 14
      rearrangements was significantly higher in NBS patients than in A-T patients (p <
      0.0005). Inv(7) was amongst the most frequently detected aberration in NBS cells
      as it is in A-T cells. Large clones of cells with rearrangements of chromosome 14
      were rare in NBS. Of the first 19 reported patients eight have already developed
      a malignancy: seven a lymphoma and one a meningioma. It is noteworthy that both
      the tendency to express rearrangements of chromosomes 7 and 14 and the tendency
      to develop a malignancy is much higher in NBS than in A-T. Whether there is any
      causal relationship is as yet unknown.

PMID- 27687099
TI  - Functional complementation studies with X-ray-sensitive mutants of Chinese
      hamster cells closely resembling ataxia-telangiectasia cells.
AB  - In order to isolate a human gene complementing the defect in A-T-like hamster
      cell mutants, the mutants were used as recipients for genomic DNA transfection,
      using either HeLa chromosomal DNA or DNA from a human cosmid library. Three
      primary transformants with an intermediate X-ray sensitivity and almost normal
      sensitivity to MMS, but retaining radioresistant DNA synthesis (RDS), were
      obtained. To identify the human chromosome that complements the defect in the A-T
      like mutants, and to assess the degree of complementation for survival and RDS,
      microcell-mediated chromosome transfer was used. At least 20 independent hybrid
      clones between the mutant and each one of the human chromosomes 1, 2, 4, 5, 15,
      17 or 18 were isolated. All hybrid clones remained X-ray sensitive, except one
      with chromosome 4, and another with chromosome 15, both showing an intermediate X
      ray sensitivity. By using in situ hybridization we found that this partial
      correction was due to the presence of a mouse chromosome. In these two hybrids
      containing the mouse chromosome together with human chromosome 4 or 15, RDS was
      fully complemented only in the hybrid with chromosome 4 but not in the one
      containing chromosome 15, suggesting that RDS and X-ray sensitivity may be
      complemented independently.

PMID- 27687100
TI  - After-thoughts and conclusions on the nature of the A-T gene.

PMID- 27687101
TI  - Clinical and genetic features of ataxia-telangiectasia.
AB  - There are several variants of ataxia-telangiectasia (A-T) : classical A-T with
      marked radiation sensitivity; classical A-T with intermediate levels of radiation
      sensitivity; mild A-T with intermediate levels of radiation sensitivity; A-T
      without telangiectasia; A-T without oculomotor apraxia; and A-T with
      microcephaly. These disorders are probably caused by different allelic mutations,
      because affected sibs resemble the index patients, and because there is an
      association of certain haplo- types of 11 q22-23 with specific phenotypes. The
      Nijmegen Breakage Syndrome, with its lack of ataxia, seems on clinical grounds to
      be a different disorder. Although A-T is almost always inherited as an autosomal
      recessive, there are some unusual features; an unexpectedly low parental
      consanguinity rate, an incidence in sibs that is <0-25, and occurrence of disease
      in many different races and in the offspring of mixed race unions. Moreover,
      looking at haplotypes from 63 UK patients, there is a remarkably low incidence of
      homozygosity. An autosomal recessive condition that is deficient in parental
      consanguinity, and in homozygosity for the region around the gene, can be
      explained by J. H. Edwards' hyopothesis that homozygosity for alleles at a
      neighbouring locus are lethal early in embryogenesis. Other possible mechanisms
      to explain the unusual genetic features are discussed.

PMID- 27687102
TI  - Ataxia-telangiectasia in Italy: genetic analysis.
AB  - Genetic analysis was performed on 72 Italian A-T families ascertained through 91
      probands. The frequency of the A-T gene was estimated through Dahlberg's formula,
      which uses the frequencies of first cousin marriages among the patients' parents
      and in the general population. Data on consanguinity in the general population
      were obtained from the collection of Catholic Church dispensations for the period
      1910-1964. Accurate estimates of the disease frequency were made by subdividing
      data into 5-year periods and between provinces, in order to take into account
      temporal (decrease over time) and spatial (higher frequency in Southern Italy)
      heterogeneity. The estimate of the gene frequency for the whole sample was q =
      0.012 +/- 0.0065, corresponding to a heterozygote frequency of 2*34% and to a
      disease frequency of 1 in 7090. When considering q before and after 1970, there
      was an apparent increase of heterozygote frequency from 1.69 to 3.43%, perhaps
      due to a better ascertainment of the disease in the latter period. A segregation
      ratio of 0.249 +/- 0.043 was obtained by analyzing the offspring of the 72
      families under the model of incomplete multiple selection. This value is not
      significantly different from 0.25, as expected for an autosomal recessive
      disease.

PMID- 27687104
TI  - Genetic and physical mapping of the ataxia-telangiectasia locus on chromosome
      Ilq22-q23.
AB  - The identification of A-T gene(s) using both positional and functional cloning
      techniques has been a major objective in A-T research over the past 10 years.
      Functional cloning, using complementation of the radiosensitivity phenotype, has
      met with some success, although technical problems remain to be overcome. Recent
      progress, however, in both genetic and physical mapping of the A-T locus on
      chromosome lIq22-q23, described in this review, suggests that the positional
      cloning of candidate genes should be achieved in the very near future. The region
      of the chromosome containing the gene(s) has been identified, and is no more than
      1-6 Mb in size. The detailed physical characterization of this region, as a
      preliminary to candidate gene isolation, is now underway. There are, however,
      still some unresolved issues, most notably the existence of four A-T
      complementation groups, with the resulting supposition that these equate to a
      number of different genes. Although genetic linkage evidence does not support the
      hypothesis of genetic heterogeneity, the possibility of a cluster of genes at the
      11 q22-23 locus cannot be ruled out. It is likely that the explanations for this
      and other problems such as discrepancies in expected levels of consanguinity, and
      difficulties in the classification of atypical phenotypes will become much more
      obvious once a gene or genes have been cloned.

PMID- 27687103
TI  - A haplotype common to intermediate radiosensitivity variants of ataxia
      telangiectasia in the UK.
AB  - In a study of ataxia-telangiectasia (A-T) in the UK, patients in 10 out of 60
      families were shown to have a much lower level of chromosomal radiosensitivity
      compared with the majority of patients. In some patients the level of
      radiosensitivity was hardly distinguishable from normal. Patients in this group,
      however, could be distinguished clinically from the majority either by the later
      onset of severe cerebellar features or the slower rate of progress of the
      disorder. By using highly polymorphic microsatellite repeat markers a chromosome
      llq22-23 haplotype common to the majority of these patients, and not occurring in
      any non-A-T chromosome in 60 families, was identified on one chromosome. The
      haplotype probably defines the region of the A-T gene in these families and the
      mutation associated with this haplotype may be much less severe than the second
      mutation thereby producing the slightly milder phenotype.

PMID- 27687105
TI  - Preface.

PMID- 27687107
TI  - Physical and genetic mapping at the ATA/ATC locus on chromosome 11q22-23.
AB  - Genetic heterogeneity in ataxia-telangiectasia (A-T) points to four different
      genes responsible for this disease. The two major A-T genes, ATA and ATC, were
      localized by genetic analysis close to each other on chromosome 11q22-23,
      prompting efforts of positional cloning. Essential steps in positional cloning
      are long-range cloning of the genomic region of interest, and derivation of
      highly polymorphic markers that would allow further reduction of the interval
      carrying the A-T gene. We constructed genomic contigs across the D11S611-D1S424
      region harbouring the ATA and ATC genes in yeast artificial chromosome (YAC)
      vectors. These contigs were used as a fine mapping tool and enabled us to
      localize along the A-T region, eight microsatellite markers generated randomly by
      genome mapping centres. In addition, we used specific YAC clones to generate five
      new microsatellite markers based on polymorphic CA repeats. Recombination mapping
      based on Israeli A-T families indicates that the ATC gene is distal to the locus
      D11S1817. Further linkage analysis using these markers is expected to reduce the
      major A-T locus considerably to a size appropriate for cosmid cloning and
      identification of transcribed sequences.

PMID- 27687106
TI  - Genetic haplotyping of ataxia-telangiectasia families localizes the major gene to
      an ~850 kb region on chromosome 11 q23.1.
AB  - The genotyping data given localize the major A-T gene to an ~ 850 kb region. They
      also localize the group A A-T gene (ATA) to a region that contains the ~ 850 kb
      region. They are compatible with linking A-TFresno to 11 q22-23. NBS-V2 does not
      link to this region. Four non-linking families contain only single affecteds,
      suggesting that these may be spontaneous mutations rather than evidence for an A
      T gene outside the 11 q22-23 region. Finally, two other non-linking families
      contain recombinant haplotypes that are compatible with a second A-T gene at
      llq22-23, slightly distal to the ~ 850 kb region. However, convincing evidence
      for a second gene is still lacking.

PMID- 27687108
TI  - DNA marker D11S384 shows zero recombination with the ataxia-telangiectasia locus
      in North American families.
AB  - At the genetic locus D11S384, one probe detects a Taql RFLP and another detects a
      RFMP. In 52 pedigrees of North American A-T patients, parental haplotypes based
      on these two bi-allelic systems have a heterozygosity of 0.69 and a PIC of 0.64.
      No recombinant events between D11S384 and the A-T locus were detected in the 43
      pedigrees in which this marker locus was informative.

PMID- 27687109
TI  - Expression of a candidate ataxia-telangieetasia group D gene in cultured
      fibroblast cell lines and human tissues.
AB  - A candidate gene for ataxia-telangiectasia group D (.ATDC) has been cloned (Kapp
      et al. 1992), sequenced and found to be a member of a recently reported gene
      family (Leonhardt et al. 1994). Transcriptional behaviour of ATDC has been
      examined in a number of cell lines and human tissues using a 3-0 kb cloned cDNA
      as a probe. Three normal and two ataxia-telangiectasia (A-T) group D, non
      transformed fibroblast cell lines produced a 2-4 kb mRNA transcript. The size of
      mRNA transcripts seen and the level of expression differ in different human
      tissues. Many tissues have multiple transcripts of ATDC and the most prominent
      transcripts observed were 3'0, 2-4 and 1-6 kb. Two out of three SV-40 transformed
      normal and one SV-40-transformed A-T group D fibroblast cell lines demonstrated
      no transcription of ATDC by RNA blotting analysis. These results suggest that SV
      40 transformation may affect the expression of ATDC. Reverse transcription-
      polymerase chain reaction analysis showed that ATDC was expressed at low levels
      in all of these cells. Additional Northern blot analysis demonstrated that X
      irradiation with 10 Gy had no effect on ATDC expression at 1, 4 and 24h after
      irradiation in either SV-40-transformed normal or in SV-40-transformed A-T group
      D fibroblast cell lines. Further understanding of ATDC will require cloning of
      additional transcripts and studies of ATDC protein behaviour.

PMID- 27687110
TI  - Expression of the candidate A-T gene ATDC is not detectable in a human cell line
      with a normal response to ionizing radiation.
AB  - Nucleotide sequence analysis of a candidate gene for A-T group D {ATDC)
      demonstrated that it is related to a group of proteins that contain both zinc
      finger and leucine zipper motifs. The presence of a leucine zipper suggested that
      this protein might form homodimers, and this was confirmed by means of the two
      hybrid system in yeast. The activity of some proteins that form homodimers can be
      effectively eliminated by overexpression of inactive forms of the protein that
      bind to the wild-type protein to create a dominant negative phenotype. An ATDC
      cDNA containing a 37 amino acid deletion in the zinc finger region (ATDCDelta)
      was therefore transfected into colorectal carcinoma human tumour cells (RKO) to
      determine whether its expression would produce a response to radiation similar to
      that seen in A-T cells. RKO cells have been shown to have normal radiosensitivity
      and cell cycle regulation and, therefore, seemed ideal for this study. Despite
      the fact that the A-T gene has been found to be important in the radiation damage
      response, no ATDC mRNA transcripts were detectable in the RKO cell line. In
      addition, the RKO subclones expressing the ATDCDelta mRNA showed no change in
      radiosensitivity or cell cycle regulation. These results do not support the
      conclusion that ATDC is an A-T gene, and suggest that the ATDC protein acts
      indirectly to suppress radiosensitivity in A-T cells.

PMID- 27687111
TI  - Cellular radiosensitivity tn ataxia-telangiectasia.
AB  - Hypersensitivity to both the cell-killing and chromosome-damaging effects of
      ionizing radiations, and other agents causing DNA breakage, is a consistent
      feature of cells from individuals with the cancer-prone disorder
      ataxiatelangiectasia (A-T). Evidence for a defect in DNA strand break rejoining
      is slight, but a higher-than-normal level of chromosomal breaks persists in
      irradiated A-T cells. There is also evidence for elevated frequencies of DNA
      recombination and deletion mutation in A-T cells; these responses may be linked
      through a loss of fidelity in rejoining DNA breaks through recombination
      mechanisms. Additionally the regulation of cell-cycle responses is altered in A-T
      cells: in all phases of the cycle there is some loss of 'checkpoint' function
      shortly after irradiation, allowing cells to continue cycling despite extensive
      DNA damage. However, on present evidence, radiation hypersensitivity cannot be
      explained simply by this loss of regulatory function. It is suggested that the A
      T gene product acts in the early stages of a DNA damage-recognition pathway,
      normally interacting with regulatory proteins such as p53, but also with proteins
      involved in the processing of DNA breaks. Reduced efficiency in this type of
      signalling function could well explain the link between radiosensitivity and
      cancer proneness.

PMID- 27687112
TI  - V(D)J Recombination and ataxia-telangiectasia: a Review.
AB  - I review one aspect of the A-T phenotype, the remarkable and fascinating increase
      of lymphocytes carrying chromosomal aberrations caused by V(D)J site-specific
      recombination. The review is organized to first present the facts of V(D)J
      recombination and the findings in this regard in A-T patients. Other populations
      that demonstrate similar increases in such chromosomal aberrations are then
      presented and a hypothesis is offered as to the basis and relevance of these
      increases vis-a-vis A-T. The contribution of V(D)J recombination to the clonal
      proliferations and frank lymphoid malignancies seen in A-T patients is briefly
      discussed. I conclude with some speculative comments extending the observations
      presented into a more global consideration of a possible function of an A-T gene.

PMID- 27687113
TI  - How RNA modification allows non-conventional decoding in mitochondria.

PMID- 27687114
TI  - Non-invasive positive pressure ventilation for acute asthma in children.
AB  - BACKGROUND: Asthma is one of the most common reasons for hospital admission among
      children and constitutes a significant economic burden. Use of non-invasive
      positive pressure ventilation (NPPV) in the care of children with acute asthma
      has increased even though evidence supporting the intervention has been
      considered weak and clinical guidelines do not recommend the intervention. NPPV
      might be an effective intervention for acute asthma, but no systematic review has
      been conducted to assess the effects of NPPV as an add-on therapy to usual care
      in children with acute asthma. OBJECTIVES: To assess the benefits and harms of
      NPPV as an add-on therapy to usual care (e.g. bronchodilators and
      corticosteroids) in children with acute asthma. SEARCH METHODS: We identified
      trials from the Cochrane Airways Group Specialised Register (CAGR). The Register
      contains trial reports identified through systematic searches of bibliographic
      databases, including the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, Embase, CINAHL, AMED and PsycINFO, and by handsearching of
      respiratory journals and meeting abstracts. We also conducted a search of
      ClinicalTrials.gov (www.ClinicalTrials.gov) and the WHO trials portal
      (www.who.int/ictrp/en/). We searched all databases from their inception to
      February 2016, with no restriction on language of publication. SELECTION
      CRITERIA: We included randomised clinical trials (RCTs) assessing NPPV as add-on
      therapy to usual care versus usual care for children (age < 18 years)
      hospitalised for an acute asthma attack. DATA COLLECTION AND ANALYSIS: Two review
      authors independently screened titles and abstracts. We retrieved all relevant
      full-text study reports, independently screened the full text, identified trials
      for inclusion and identified and recorded reasons for exclusion of ineligible
      trials. We resolved disagreements through discussion or, if required, consulted a
      third review author. We recorded the selection process in sufficient detail to
      complete a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      analyses) flow diagram and 'Characteristics of excluded studies' table. We
      identified the risk of bias of included studies to reduce the risk of systematic
      error. We contacted relevant study authors when data were missing. MAIN RESULTS:
      We included two RCTs that randomised 20 participants to NPPV and 20 participants
      to control. We assessed both studies as having high risk of bias; both trials
      assessed effects of bilateral positive airway pressure (BiPAP). Neither trial
      used continuous positive airway pressure (CPAP). Controls received standard care.
      Investigators reported no deaths and no serious adverse events (Grades of
      Recommendation, Assessment, Development and Evaluation (GRADE): very low quality
      of evidence due to serious risk of bias and serious imprecision of results). Both
      trials showed a statistically significant reduction in symptom score. One trial
      did not report a standard deviation (SD), but by using an estimated SD, we found
      a statistically significantly reduced asthma symptom score (mean difference (MD) 
      2.50, 95% confidence interval (CI) -4.70 to -0.30, P = 0.03, 19 participants,
      GRADE: very low quality of evidence). In the other trial, NPPV was associated
      with a lower total symptom score (5.6 vs 1.9, 16 participants, very low quality
      of evidence) before cross-over, but investigators did not report an SD, nor could
      it be estimated from the first phase of the trial, before the cross-over. These
      gains could be clinically relevant, as a reduction of three or more points in
      symptom score is considered a clinically meaningful change. Researchers
      documented five dropouts (12.5%), four of which were due to intolerance to NPPV,
      and one to respiratory failure requiring intubation. Owing to insufficient
      reporting in the latter trial and use of different scoring systems, it was not
      possible to conduct a meta-analysis nor a Trial Sequential Analysis. AUTHORS'
      CONCLUSIONS: Current evidence does not permit confirmation or rejection of the
      effects of NPPV for acute asthma in children. Large RCTs with low risk of bias
      are warranted.

PMID- 27687115
TI  - BEN domain protein Elba2 can functionally substitute for linker histone H1 in
      Drosophila in vivo.
AB  - Metazoan linker histones are essential for development and play crucial roles in
      organization of chromatin, modification of epigenetic states and regulation of
      genetic activity. Vertebrates express multiple linker histone H1 isoforms, which
      may function redundantly. In contrast, H1 isoforms are not present in Dipterans,
      including D. melanogaster, except for an embryo-specific, distantly related
      dBigH1. Here we show that Drosophila BEN domain protein Elba2, which is expressed
      in early embryos and was hypothesized to have insulator-specific functions, can
      compensate for the loss of H1 in vivo. Although the Elba2 gene is not essential,
      its mutation causes a disruption of normal internucleosomal spacing of chromatin
      and reduced nuclear compaction in syncytial embryos. Elba2 protein is distributed
      ubiquitously in polytene chromosomes and strongly colocalizes with H1. In H1
      depleted animals, ectopic expression of Elba2 rescues the increased lethality and
      ameliorates abnormalities of chromosome architecture and heterochromatin
      functions. We also demonstrate that ectopic expression of BigH1 similarly
      complements the deficiency of H1 protein. Thus, in organisms that do not express
      redundant H1 isoforms, the structural and biological functions performed by
      canonical linker histones in later development, may be shared in early embryos by
      weakly homologous proteins, such as BigH1, or even unrelated, non-homologous
      proteins, such as Elba2.

PMID- 27687116
TI  - Experiments with More Than One Random Factor: Designs, Analytic Models, and
      Statistical Power.
AB  - Traditional methods of analyzing data from psychological experiments are based on
      the assumption that there is a single random factor (normally participants) to
      which generalization is sought. However, many studies involve at least two random
      factors (e.g., participants and the targets to which they respond, such as words,
      pictures, or individuals). The application of traditional analytic methods to the
      data from such studies can result in serious bias in testing experimental
      effects. In this review, we develop a comprehensive typology of designs involving
      two random factors, which may be either crossed or nested, and one fixed factor,
      condition. We present appropriate linear mixed models for all designs and develop
      effect size measures. We provide the tools for power estimation for all designs.
      We then discuss issues of design choice, highlighting power and feasibility
      considerations. Our goal is to encourage appropriate analytic methods that
      produce replicable results for studies involving new samples of both participants
      and targets.

PMID- 27687118
TI  - Mindfulness Interventions.
AB  - Mindfulness interventions aim to foster greater attention to and awareness of
      present moment experience. There has been a dramatic increase in randomized
      controlled trials (RCTs) of mindfulness interventions over the past two decades.
      This article evaluates the growing evidence of mindfulness intervention RCTs by
      reviewing and discussing (a) the effects of mindfulness interventions on health,
      cognitive, affective, and interpersonal outcomes; (b) evidence-based applications
      of mindfulness interventions to new settings and populations (e.g., the
      workplace, military, schools); (c) psychological and neurobiological mechanisms
      of mindfulness interventions; (d) mindfulness intervention dosing considerations;
      and (e) potential risks of mindfulness interventions. Methodologically rigorous
      RCTs have demonstrated that mindfulness interventions improve outcomes in
      multiple domains (e.g., chronic pain, depression relapse, addiction). Discussion
      focuses on opportunities and challenges for mindfulness intervention research and
      on community applications.

PMID- 27687117
TI  - Memory: Organization and Control.
AB  - A major goal of memory research is to understand how cognitive processes in
      memory are supported at the level of brain systems and network representations.
      Especially promising in this direction are new findings in humans and animals
      that converge in indicating a key role for the hippocampus in the systematic
      organization of memories. New findings also indicate that the prefrontal cortex
      may play an equally important role in the active control of memory organization
      during both encoding and retrieval. Observations about the dialog between the
      hippocampus and prefrontal cortex provide new insights into the operation of the
      larger brain system that serves memory.

PMID- 27687120
TI  - Culture Three Ways: Culture and Subcultures Within Countries.
AB  - Culture can be thought of as a set of everyday practices and a core theme
      individualism, collectivism, or honor-as well as the capacity to understand each
      of these themes. In one's own culture, it is easy to fail to see that a cultural
      lens exists and instead to think that there is no lens at all, only reality.
      Hence, studying culture requires stepping out of it. There are two main methods
      to do so: The first involves using between-group comparisons to highlight
      differences and the second involves using experimental methods to test the
      consequences of disruption to implicit cultural frames. These methods highlight
      three ways that culture organizes experience: (a) It shields reflexive processing
      by making everyday life feel predictable, (b) it scaffolds which cognitive
      procedure (connect, separate, or order) will be the default in ambiguous
      situations, and (c) it facilitates situation-specific accessibility of alternate
      cognitive procedures. Modern societal social-demographic trends reduce
      predictability and increase collectivism and honor-based go-to cognitive
      procedures.

PMID- 27687121
TI  - The Structure of Social Cognition: In(ter)dependence of Sociocognitive Processes.
AB  - Social cognition is a topic of enormous interest and much research, but we are
      far from having an agreed taxonomy or factor structure of relevant processes. The
      aim of this review is to outline briefly what is known about the structure of
      social cognition and to suggest how further progress can be made to delineate the
      in(ter)dependence of core sociocognitive processes. We focus in particular on
      several processes that have been discussed and tested together in typical and
      atypical (notably autism spectrum disorder) groups: imitation, biological motion,
      empathy, and theory of mind. We consider the domain specificity/generality of
      core processes in social learning, reward, and attention, and we highlight the
      potential relevance of dual-process theories that distinguish systems for
      fast/automatic and slow/effortful processing. We conclude with methodological and
      conceptual suggestions for future progress in uncovering the structure of social
      cognition.

PMID- 27687123
TI  - How Power Affects People: Activating, Wanting, and Goal Seeking.
AB  - Sociocognitive research has demonstrated that power affects how people feel,
      think, and act. In this article, I review literature from social psychology,
      neuroscience, management, and animal research and propose an integrated framework
      of power as an intensifier of goal-related approach motivation. A growing
      literature shows that power energizes thought, speech, and action and orients
      individuals toward salient goals linked to power roles, predispositions, tasks,
      and opportunities. Power magnifies self-expression linked to active parts of the
      self (the active self), enhancing confidence, self-regulation, and prioritization
      of efforts toward advancing focal goals. The effects of power on cognitive
      processes, goal preferences, performance, and corruption are discussed, and its
      potentially detrimental effects on social attention, perspective taking, and
      objectification of subordinates are examined. Several inconsistencies in the
      literature are explained by viewing power holders as more flexible and dynamic
      than is usually assumed.

PMID- 27687122
TI  - Numerical Development.
AB  - In this review, we attempt to integrate two crucial aspects of numerical
      development: learning the magnitudes of individual numbers and learning
      arithmetic. Numerical magnitude development involves gaining increasingly precise
      knowledge of increasing ranges and types of numbers: from nonsymbolic to small
      symbolic numbers, from smaller to larger whole numbers, and from whole to
      rational numbers. One reason why this development is important is that precision
      of numerical magnitude knowledge is correlated with, predictive of, and causally
      related to both whole and rational number arithmetic. Rational number arithmetic,
      however, also poses challenges beyond understanding the magnitudes of the
      individual numbers. Some of these challenges are inherent; they are present for
      all learners. Other challenges are culturally contingent; they vary from country
      to country and classroom to classroom. Generating theories and data that help
      children surmount the challenges of rational number arithmetic is a promising and
      important goal for future numerical development research.

PMID- 27687119
TI  - Learning, Reward, and Decision Making.
AB  - In this review, we summarize findings supporting the existence of multiple
      behavioral strategies for controlling reward-related behavior, including a
      dichotomy between the goal-directed or model-based system and the habitual or
      model-free system in the domain of instrumental conditioning and a similar
      dichotomy in the realm of Pavlovian conditioning. We evaluate evidence from
      neuroscience supporting the existence of at least partly distinct neuronal
      substrates contributing to the key computations necessary for the function of
      these different control systems. We consider the nature of the interactions
      between these systems and show how these interactions can lead to either adaptive
      or maladaptive behavioral outcomes. We then review evidence that an additional
      system guides inference concerning the hidden states of other agents, such as
      their beliefs, preferences, and intentions, in a social context. We also describe
      emerging evidence for an arbitration mechanism between model-based and model-free
      reinforcement learning, placing such a mechanism within the broader context of
      the hierarchical control of behavior.

PMID- 27687124
TI  - The value of poly-urethane cuffed endotracheal tubes.

PMID- 27687126
TI  - Atypical presentations of acute disseminated encephalomyelitis (ADEM) in HIV
      infection.
AB  - Acute disseminated encephalomyelitis is a monophasic demyelinating disorder of
      the central nervous system associated with various viral infections including HIV
      infection. We present the findings of seven HIV-infected patients with mild to
      moderate immunosuppression presenting with atypical features. Four patients had a
      multiphasic course; three patients had tumefactive lesions, and two patients had
      corpus callosum lesions. Two patients with the multiphasic course also had
      tumefactive lesions. Their clinical and radiological findings are presented.
      Despite the few cases, we propose that the dysimmune process lying between marked
      immunosuppression (CD4 < 200 cells/MUL) and normal CD4 counts (CD4 > 500
      cells/MUL) might be responsible for these atypical presentations.

PMID- 27687127
TI  - The role of background diet on the effects of eicosapentaenoic acid and
      docosahexaenoic acid supplementation in healthy pre-menopausal women: a
      randomized, cross-over, controlled study.
AB  - BACKGROUND: The links between dietary fat intake, polyunsaturated fatty acid
      intake and breast cancer risk remain equivocal, with some studies pointing to
      improvements in risk upon omega-3 supplementation. However, the background diet
      is poorly controlled in most studies, potentially confounding this link.
      Therefore, this study examined the hypothesis that in order to see the benefits
      of omega-3 fatty acid supplementation, the background diet must be low in fat.
      METHODS: Of the 56 healthy, pre-menopausal women randomized to one of two
      experimental arms, consisting of a two-treatment, randomized, cross-over design,
      41 completed the 10 month intervention. The two diet phases (habitual and low
      fat) were separated by a washout phase, each lasting 3 menstrual cycles. During
      each diet phase, women were supplemented with 1.2 g eicosapentaenoic acid +
      docosahexaenoic acid per day. RESULTS: Red blood cell fatty acid composition
      indicated that more eicosapentaenoic acid and docosahexaenoic acid was
      incorporated in the low-fat diet than the habitual diet, though both diet phases
      resulted in significant increases in the omega-3 to omega-6 ratio. In the context
      of omega-3 supplementation in breast cancer risk reduction, we also measured
      fatty acid incorporation into nipple aspirate fluid. Similar changes to red blood
      cells were noted in nipple aspirate fluid, with higher incorporation of
      eicosapentaenoic acid in the low-fat diet phase. CONCLUSIONS: These data suggest
      that the total level of dietary fat has some direct impact on fatty acid
      partitioning in addition to the recognized importance of fatty acid ratios, and
      supports the hypothesis that dietary fat intake must be considered a confounder
      in supplementation trials. Additionally, we demonstrate that n3 supplementation
      both reaches and imparts improvements in lipid content and n3:n6 at the target
      breast tissue. TRIAL REGISTRATION: Trial was been retrospectively registered at
      clinicaltrials.gov (Reg NCT02816125 ).

PMID- 27687128
TI  - Allergen immunotherapy (AIT) for the multiple-pollen sensitive patient.
AB  - INTRODUCTION: The majority of allergic subjects are polysensitized. In Europe,
      allergy immunotherapy (AIT) in these patients is usually limited to their single
      clinically most troublesome allergy while in the U.S. the immunotherapy
      prescription usually includes all allergen extracts to which the patient has
      evidence of clinical sensitivity. Areas covered: This article will review the
      evidence supporting the U.S. practice. It will also review the major new
      development in the management of polysensitized patients, the introduction of
      component-resolved diagnosis (CRD). Expert commentary: This allows, in many
      cases, distinguishing in polysensitized patients between sensitization to the
      major allergens of several unrelated allergen extracts and to panallergens that
      cause broad patterns of cross-reactivity.

PMID- 27687125
TI  - Electroacupuncture in conscious free-moving mice reduces pain by ameliorating
      peripheral and central nociceptive mechanisms.
AB  - Integrative approaches such as electroacupuncture, devoid of drug effects are
      gaining prominence for treating pain. Understanding the mechanisms of
      electroacupuncture induced analgesia would benefit chronic pain conditions such
      as sickle cell disease (SCD), for which patients may require opioid analgesics
      throughout life. Mouse models are instructive in developing a mechanistic
      understanding of pain, but the anesthesia/restraint required to administer
      electroacupuncture may alter the underlying mechanisms. To overcome these
      limitations, we developed a method to perform electroacupuncture in conscious,
      freely moving, unrestrained mice. Using this technique we demonstrate a
      significant analgesic effect in transgenic mouse models of SCD and cancer as well
      as complete Freund's adjuvant-induced pain. We demonstrate a comprehensive
      antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both
      genders. Interestingly, individual mice showed a variable response to
      electroacupuncture, categorized into high-, moderate-, and non-responders.
      Mechanistically, electroacupuncture significantly ameliorated inflammatory and
      nociceptive mediators both peripherally and centrally in sickle mice correlative
      to the antinociceptive response. Application of sub-optimal doses of morphine in
      electroacupuncture-treated moderate-responders produced equivalent
      antinociception as obtained in high-responders. Electroacupuncture in conscious
      freely moving mice offers an effective approach to develop a mechanism-based
      understanding of analgesia devoid of the influence of anesthetics or restraints.

PMID- 27687131
TI  - Corrigendum: Autophagy-associated alpha-arrestin signaling is required for
      conidiogenous cell development in Magnaporthe oryzae.

PMID- 27687129
TI  - Flux of signalling endosomes undergoing axonal retrograde transport is encoded by
      presynaptic activity and TrkB.
AB  - Axonal retrograde transport of signalling endosomes from the nerve terminal to
      the soma underpins survival. As each signalling endosome carries a quantal amount
      of activated receptors, we hypothesized that it is the frequency of endosomes
      reaching the soma that determines the scale of the trophic signal. Here we show
      that upregulating synaptic activity markedly increased the flux of plasma
      membrane-derived retrograde endosomes (labelled using cholera toxin subunit-B:
      CTB) in hippocampal neurons cultured in microfluidic devices, and live Drosophila
      larval motor neurons. Electron and super-resolution microscopy analyses revealed
      that the fast-moving sub-diffraction-limited CTB carriers contained the TrkB
      neurotrophin receptor, transiently activated by synaptic activity in a BDNF
      independent manner. Pharmacological and genetic inhibition of TrkB activation
      selectively prevented the coupling between synaptic activity and the retrograde
      flux of signalling endosomes. TrkB activity therefore controls the encoding of
      synaptic activity experienced by nerve terminals, digitalized as the flux of
      retrogradely transported signalling endosomes.

PMID- 27687130
TI  - Differential roles of NF-Y transcription factor in ER chaperone expression and
      neuronal maintenance in the CNS.
AB  - The mammalian central nervous system (CNS) contains various types of neurons with
      different neuronal functions. In contrast to established roles of cell type
      specific transcription factors on neuronal specification and maintenance, whether
      ubiquitous transcription factors have conserved or differential neuronal function
      remains uncertain. Here, we revealed that inactivation of a ubiquitous factor NF
      Y in different sets of neurons resulted in cell type-specific neuropathologies
      and gene downregulation in mouse CNS. In striatal and cerebellar neurons, NF-Y
      inactivation led to ubiquitin/p62 pathologies with downregulation of an
      endoplasmic reticulum (ER) chaperone Grp94, as we previously observed by NF-Y
      deletion in cortical neurons. In contrast, NF-Y inactivation in motor neurons
      induced neuronal loss without obvious protein deposition. Detailed analysis
      clarified downregulation of another ER chaperone Grp78 in addition to Grp94 in
      motor neurons, and knockdown of both ER chaperones in motor neurons recapitulated
      the pathology observed after NF-Y inactivation. Finally, additional
      downregulation of Grp78 in striatal neurons suppressed ubiquitin accumulation
      induced by NF-Y inactivation, implying that selective ER chaperone downregulation
      mediates different neuropathologies. Our data suggest distinct roles of NF-Y in
      protein homeostasis and neuronal maintenance in the CNS by differential
      regulation of ER chaperone expression.

PMID- 27687132
TI  - A Cure For Hemophilia: the Promise Becomes a Reality.

PMID- 27687135
TI  - A Self-restricted CRISPR System to Reduce Off-target Effects.

PMID- 27687136
TI  - Man's Best Friend: Utilizing Naturally Occurring Tumors in Dogs to Improve
      Chimeric Antigen Receptor T-cell Therapy for Human Cancers.

PMID- 27687137
TI  - Highly Selective Tau-SPECT Imaging Probes for Detection of Neurofibrillary
      Tangles in Alzheimer's Disease.
AB  - Neurofibrillary tangles composed of aggregates of hyperphosphorylated tau
      proteins are one of the neuropathological hallmarks of Alzheimer's disease (AD)
      in addition to the deposition of beta-amyloid plaques. Since the deposition of
      tau aggregates is closely associated with the severity of AD, the in vivo
      detection of tau aggregates may be useful as a biomarker for the diagnosis and
      progression of AD. In this study, we designed and synthesized a new series of
      radioiodinated benzoimidazopyridine (BIP) derivatives, and evaluated their
      utility as single photon emission computed tomography (SPECT) imaging agents
      targeting tau aggregates in AD brains. Five radioiodinated BIP derivatives were
      successfully prepared in high radiochemical yields and purities. In in vitro
      autoradiographic studies using postmortem AD brains, all BIP derivatives
      displayed high accumulation of radioactivity in the brain sections with abundant
      neurofibrillary tangles, while no marked radioactivity accumulation was observed
      in the brain sections with only beta-amyloid aggregates, indicating that the BIP
      derivatives exhibited selective binding to tau aggregates. Biodistribution
      studies in normal mice showed high brain uptake at 2 min postinjection (3.5-4.7%
      ID/g) and rapid clearance at 60 min postinjection (0.04-0.23% ID/g), which is
      highly desirable for tau imaging agents. The results of the present study suggest
      that [123I]BIP derivatives may be useful SPECT agents for the in vivo imaging of
      tau aggregates in AD.

PMID- 27687138
TI  - Reply to: Gabapentin: A promising therapy for uremic pruritus in hemodialysis
      patients: A randomized-controlled trial and review of literature.

PMID- 27687139
TI  - Inhibitory actions of selected natural substances on formation of advanced
      glycation endproducts and advanced oxidation protein products.
AB  - BACKGROUND: Advanced glycation endproducts (AGE) and advanced oxidation protein
      products (AOPP) arise as a result of excessive glycation and oxidation processes
      of proteins in hyperglycemia and oxidative stress conditions respectively, both
      in vivo and in vitro. In vivo these processes are especially intensified in
      patients with diabetes, and the adverse effects of AGE and AOPP are particularly
      unfavorable for the pathogenesis and aggravate the biochemical disturbances and
      clinical complications of diabetes. Total AGE and AOPP (T-AGE and T-AOPP) are
      heterogeneous groups of compounds, and they can be divided into two main
      fractions: high- and low-molecular-weight, i.e. HMW-AGE and HMW-AOPP as well as
      LMW-AGE and LMW-AOPP. Therefore it is important to find natural substances that
      will prevent formation of total AGE and AOPP and their high- and low-molecular
      weight fractions and thereby reduce their adverse effects on tissues and organs.
      METHOD: Selected natural substances and dietary supplements such as vitamin C,
      aminoguanidine, quercetin and green tea as well as the multicompound formulations
      Padma Circosan and Padma 28 were tested in an in vitro model using bovine serum
      albumin (BSA). Fluorescence of T-, HMW- and LMW-AGE and concentration of T-, HMW-
      and LMW-AOPP were measured after incubation with these substances. RESULTS: In
      the examined concentrations quercetin showed the greatest degree of inhibition
      for T-AGE (60.5 %) as well as for HMW-AGE (79.5 %), while in the case of LMW-AGE
      the greatest degree of glycation inhibition was shown by Padma Circosan (74.9 %).
      T-AOPP and HMW-AOPP were best inhibited by vitamin C (87.3 and 89.1 %
      respectively). The results obtained for LMW-AOPP are atypical, but the lowest
      concentration was observed in a sample with Padma 28. CONCLUSION: The results
      show that all tested natural compounds have inhibitory activity towards the
      formation of total and low- and high-molecular-weight forms of AGE and AOPP in
      vitro. That suggest a possible role in the prevention of diabetic complications,
      especially the multiherbal compound Padma preparations, which are especially
      effective in lowering the most dangerous, i.e. LMW fractions.

PMID- 27687140
TI  - Chemical constituents and antitumor activity from Paris polyphylla Smith var.
      yunnanensis.
AB  - Eleven compounds were isolated from the rhizomes of Paris polyphylla Smith var.
      yunnanensis. Their structures were elucidated on the basis of rigorous 1D and 2D
      NMR experiments as well as comparison with the literature data. To the best of
      our knowledge, compound 1 was only predicted by UPLC/Q-TOF MSE and the NMR
      spectroscopic data was given for the first time. The cytotoxic activities of all
      compounds on mouse B16 cells were evaluated. Among the tested molecules,
      compounds 6-9 showed strong cytotoxicities, while compound 1 did not show
      significant effect.

PMID- 27687142
TI  - Pseudoaneurysm of the anterior tibial artery after interlocking tibial nailing:
      an unexpected complication.
AB  - Anterior tibial pseudoaneurysm is a rare complication after interlocking screw
      insertion in tibial nailing. We present the case of a 28-year-old male patient
      with this complication with a 6-week delay after tibial nailing of a right tibial
      fracture type 42-A1 of the Association for the Study of Internal Fixation
      (AO/ASIF) classification. On presentation to our emergency department, the
      patient's complaints were solemnly intermittent pain and occasional swelling of
      his proximal lower leg. Deep vein thrombosis, compartment syndrome, and implant
      dislocation were ruled out, and the patient was discharged after his symptoms
      improved without further intervention. Four weeks later, the patient was
      readmitted for similar symptoms. A computed tomography (CT) angiography then
      revealed a pseudoaneurysm of the anterior tibial artery at the level of the
      proximal interlocking screw insertion. Aneurysmal sac excision with vessel repair
      was performed while reconstructing the additional dislocated proximal fibular
      fracture using standard AO/ASIF plating. Postoperatively, sufficient flow through
      the repaired vessel was documented using Doppler ultrasound and CT angiography.
      However, the patient sustained a temporal damage to the peroneal nerve after
      surgery. This case highlights the risk of a pseudoaneurysm of the anterior tibial
      artery after interlocking screw insertion as a rare but major complication of a
      routine surgical procedure. Early ultrasound diagnostics, CT angiography, or
      magnetic resonance (MR) angiogram should be performed to prevent the delay in
      diagnosis and treatment of such complications.

PMID- 27687143
TI  - Experimental and First-Principles NMR Analysis of Pt(II) Complexes With O,O'
      Dialkyldithiophosphate Ligands.
AB  - Polycrystalline bis(dialkyldithiophosphato)Pt(II) complexes of the form
      [Pt{S2P(OR)2}2] (R = ethyl, iso-propyl, iso-butyl, sec-butyl or cyclo-hexyl
      group) were studied using solid-state 31P and 195Pt NMR spectroscopy, to
      determine the influence of R to the structure of the central chromophore. The
      measured anisotropic chemical shift (CS) parameters for 31P and 195Pt afford more
      detailed chemical and structural information, as compared to isotropic CS and J
      couplings alone. Advanced theoretical modeling at the hybrid DFT level, including
      both crystal lattice and the important relativistic spin-orbit effects
      qualitatively reproduced the measured CS tensors, supported the experimental
      analysis, and provided extensive orientational information. A particular
      correction model for the non-negligible lattice effects was adopted, allowing one
      to avoid a severe deterioration of the 195Pt anisotropic parameters due to the
      high requirements posed on the pseudopotential quality in such calculations.
      Though negligible differences were found between the 195Pt CS tensors with
      different substituents R, the 31P CS parameters differed significantly between
      the complexes, implying the potential to distinguish between them. The presented
      approach enables good resolution and a detailed analysis of heavy-element
      compounds by solid-state NMR, thus widening the understanding of such systems.

PMID- 27687144
TI  - Neonatal post-haemorrhagic hydrocephalus in the UK: a survey of current practice.
AB  - OBJECTIVES: The management of neonatal post-haemorrhagic hydrocephalus (nPHH)
      varies considerably between centres and even between neurosurgeons in the same
      centre. We performed a nationwide survey to evaluate current practice in the UK
      and reviewed the evidence for each intervention. METHODS: An online semi
      structured questionnaire was emailed to all units registered on the British
      Paediatric Neurosurgery Group Mailing List. The survey consisted of 18 questions
      designed to establish the status quo in the management of nPHH, including
      preferred temporising procedure, factors guiding the timing of intervention and
      willingness to participate in a prospective study. RESULTS: A total of 24
      consultants responded to the survey. Ventricular access device (VAD), trans
      fontanelle tap, ventriculosubgaleal shunt (VSGS) and lumbar puncture (LP) were
      used by 33, 25, 17 and 17%, respectively, as the first temporising measure.
      Almost all reported that the timing of this intervention was guided by increasing
      head circumference and tense fontanelle. If the first temporising procedure
      fails, VAD, external ventricular drainage (EVD), trans-fontanelle tap, VSGS and
      other procedures (including ventriculoperitoneal (VP) shunting and endoscopic
      third ventriculostomy (ETV)) were performed by 42, 17, 13, 8 and 21%,
      respectively. Almost all respondents reported that VP shunting would be their
      preferred method of definitive cerebrospinal fluid (CSF) diversion. Almost all
      responded that they would be willing to participate in a prospective study in the
      future to determine best practice. CONCLUSION: As expected there was a
      significant heterogeneity between respondents in the initial management of nPHH
      in the UK. VAD was the most popular first and second choice temporising measure.
      On reviewing the literature, it is clear that more work still needs to be done to
      establish which temporising measure is best. There is willingness in the UK to
      participate in a study to help determine this.

PMID- 27687146
TI  - On the maintenance of genetic variation and adaptation to environmental change:
      considerations from population genomics in fishes.
AB  - The first goal of this paper was to overview modern approaches to local
      adaptation, with a focus on the use of population genomics data to detect signals
      of natural selection in fishes. Several mechanisms are discussed that may enhance
      the maintenance of genetic variation and evolutionary potential, which have been
      overlooked and should be considered in future theoretical development and
      predictive models: the prevalence of soft sweeps, polygenic basis of adaptation,
      balancing selection and transient polymorphisms, parallel evolution, as well as
      epigenetic variation. Research on fish population genomics has provided ample
      evidence for local adaptation at the genome level. Pervasive adaptive evolution,
      however, seems to almost never involve the fixation of beneficial alleles.
      Instead, adaptation apparently proceeds most commonly by soft sweeps entailing
      shifts in frequencies of alleles being shared between differentially adapted
      populations. One obvious factor contributing to the maintenance of standing
      genetic variation in the face of selective pressures is that adaptive phenotypic
      traits are most often highly polygenic, and consequently the response to
      selection should derive mostly from allelic co-variances among causative loci
      rather than pronounced allele frequency changes. Balancing selection in its
      various forms may also play an important role in maintaining adaptive genetic
      variation and the evolutionary potential of species to cope with environmental
      change. A large body of literature on fishes also shows that repeated evolution
      of adaptive phenotypes is a ubiquitous evolutionary phenomenon that seems to
      occur most often via different genetic solutions, further adding to the potential
      options of species to cope with a changing environment. Moreover, a paradox is
      emerging from recent fish studies whereby populations of highly reduced effective
      population sizes and impoverished genetic diversity can apparently retain their
      adaptive potential in some circumstances. Although more empirical support is
      needed, several recent studies suggest that epigenetic variation could account
      for this apparent paradox. Therefore, epigenetic variation should be fully
      integrated with considerations pertaining to role of soft sweeps, polygenic and
      balancing selection, as well as repeated adaptation involving different genetic
      basis towards improving models predicting the evolutionary potential of species
      to cope with a changing world.

PMID- 27687145
TI  - Frequency and predictors of estimated HIV transmissions and bacterial STI
      acquisition among HIV-positive patients in HIV care across three continents.
AB  - INTRODUCTION: Successful global treatment as prevention (TasP) requires
      identifying HIV-positive individuals at high risk for transmitting HIV, and
      having impact via potential infections averted. This study estimated the
      frequency and predictors of numbers of HIV transmissions and bacterial sexually
      transmitted infection (STI) acquisition among sexually active HIV-positive
      individuals in care from three representative global settings. METHODS: HIV
      positive individuals (n=749), including heterosexual men, heterosexual women and
      men who have sex with men (MSM) in HIV care, were recruited from Chiang Mai
      (Thailand), Rio De Janeiro (Brazil) and Lusaka (Zambia). Participants were
      assessed on HIV and STI sexual transmission risk variables, psychosocial
      characteristics and bacterial STIs at enrolment and quarterly for 12 months
      (covering 15 months). Estimated numbers of HIV transmissions per person were
      calculated using reported numbers of partners and sex acts together with
      estimates of HIV transmissibility, accounting for ART treatment and condom use.
      RESULTS: An estimated 3.81 (standard error, (SE)=0.63) HIV transmissions occurred
      for every 100 participants over the 15 months, which decreased over time. The
      highest rate was 19.50 (SE=1.68) for every 100 MSM in Brazil. In a multivariable
      model, country*risk group interactions emerged: in Brazil, MSM had 2.85 (95%
      CI=1.45, 4.25, p<0.0001) more estimated transmissions than heterosexual men and
      3.37 (95% CI=2.01, 4.74, p<0.0001) more than heterosexual women over the 15
      months. For MSM and heterosexual women, the combined 12-month STI incidence rate
      for the sample was 22.4% (95% CI=18.1%, 27.3%; incidence deemed negligible in
      heterosexual men). In the multivariable model, MSM had 12.3 times greater odds
      (95% CI=4.44, 33.98) of acquiring an STI than women, but this was not significant
      in Brazil. Higher alcohol use on the Alcohol Use Disorders Identification Test
      (OR=1.04, 95% CI=1.01, 1.08) was also significantly associated with increased STI
      incidence. In bivariate models for both HIV transmissions and STI incidence,
      higher depressive symptoms were significant predictors. CONCLUSIONS: These data
      help to estimate the potential number of HIV infections transmitted and bacterial
      STIs acquired over time in patients established in care, a group typically
      considered at lower transmission risk, and found substantial numbers of estimated
      HIV transmissions. These findings provide an approach for evaluating the impact
      (in phase 2 studies) and potentially cost-effectiveness of global TasP efforts.

PMID- 27687147
TI  - Does age matter? Comparison of neurobehavioral effects of paraquat exposure on
      postnatal and adult C57BL/6 mice.
AB  - Epidemiological studies have revealed that environmentally relevant low levels of
      paraquat (PQ) exposure is listed on the etiology of neurological disorders such
      as Parkinson's disease (PD). The behavioral effects of PQ are of current
      interest, especially when exposure occurs in the period of early stage of life.
      To characterize whether and how age affects neurobehavioral performances of mice
      after PQ exposure, 21 days postnatal (PN21) and adult male C57BL/6 mice were
      daily administrated by oral gavage with 0 mg/kg (saline, control), 5 mg/kg or 10
      mg/kg of PQ for 28 consecutive days. Survival rate and body weight were analyzed.
      Subsequently, mice were subjected to Morris water maze tests (MWM). The results
      showed that mice exposed to PQ had significantly longer latencies than those in
      the control group, with a dose-dependent manner. Furthermore, PN21 mice tended to
      have longer latencies than adult mice in the same dose group. Our data suggested
      that PQ exposure induced significant learning and memory impairment and more
      severely in PN21 mice when compared with adult mice.

PMID- 27687148
TI  - Cathepsin S contributes to microglia-mediated olfactory dysfunction through the
      regulation of Cx3cl1-Cx3cr1 axis in a Niemann-Pick disease type C1 model.
AB  - Microglia can aggravate olfactory dysfunction by mediating neuronal death in the
      olfactory bulb (OB) of a murine model of Niemann-Pick disease type C1 (NPC1), a
      fatal neurodegenerative disorder accompanied by lipid trafficking defects. In
      this study, we focused on the crosstalk between neurons and microglia to
      elucidate the mechanisms underlying extensive microgliosis in the NPC1-affected
      brain. Microglia in the OB of NPC1 mice strongly expressed CX3C chemokine
      receptor 1 (Cx3cr1), a specific receptor for the neural chemokine C-X3-C motif
      ligand 1 (Cx3cl1). In addition, a high level of Cx3cl1 was detected in NPC1 mouse
      derived CSF due to enhanced catalytic activity of Cathepsin S (Ctss), which is
      responsible for Cx3cl1 secretion. Notably, nasal delivery of Cx3cl1 neutralizing
      antibody or Ctss inhibitor could inhibit the Cx3cl1-Cx3cr1 interaction and
      support neuronal survival through the suppression of microglial activation,
      leading to an improvement in the olfactory function in NPC1 mice. Relevant in
      vitro experiments revealed that intracellular cholesterol accumulation could act
      as a strong inducer of abnormal Ctss activation and, in turn, stimulated the
      Cx3cl1-Cx3cr1 axis in microglia via p38 mitogen-activated protein kinase
      signaling. Our data address the significance of Cx3cl1-Cx3cr1 interaction in the
      development of microglial neurotoxicity and suggest that Ctss is a key upstream
      regulator. Therefore, this study contributes to a better understanding of the
      crosstalk between neurons and microglia in the development of the
      neurodegeneration and provides a new perspective for the management of olfactory
      deficits and other microglia-dependent neuropathies. GLIA 2016;64:2291-2305.

PMID- 27687149
TI  - Relationships between work-related characteristics, needs satisfaction,
      motivation and mental health in midwifery students.
AB  - The present study examined the relationships between work-related characteristics
      in internships, psychological needs satisfaction, motivation and mental health
      using a partial least squares path modeling. Midwifery students (N = 214; Mage =
      22.8 years) from three French schools completed different questionnaires online.
      Results showed (1) the importance of work resources (work control and social
      support) as protective factors of psychological needs satisfaction; and (2) the
      role of competence need satisfaction through motivation in the relationships
      between work resources and mental health. Midwifery schools should pay more
      attention to these two results, and take them into account in midwifery students'
      training.

PMID- 27687150
TI  - Structural and functional quantitative susceptibility mapping from standard fMRI
      studies.
AB  - Standard functional MRI (fMRI), which includes resting-state or paradigm-driven
      designs, is widely used in studies of brain function, aging, and disease. These
      fMRI studies typically use two-dimensional gradient echo-planar imaging, which
      inherently contains phase data that enables quantitative susceptibility mapping
      (QSM). This work focuses on the dual value of QSM within fMRI studies, by
      providing both a localized analysis of functional changes in activated tissue,
      and iron-sensitive structural maps in deep grey matter (DGM). Using a visual
      paradigm fMRI study on healthy volunteers at clinical (1.5 T) and high field
      strength (4.7 T), we perform functional analysis of magnitude and QSM time
      series, and at the same time harness structural QSM of iron-rich DGM, including
      globus pallidus, putamen, caudate head, substantia nigra, and red nucleus. The
      effects of fMRI spatial resolution and time series variation on structural DGM
      QSM are investigated. Our results indicate that structural DGM QSM is feasible
      within existing fMRI studies, provided that the voxel dimensions are equal to or
      less than 3 mm, with higher resolutions preferred. The mean DGM QSM values were
      about 40 to 220 ppb, while the interquartile ranges of the DGM QSM time series
      varied from about 3 to 9 ppb, depending on structure and resolution. In contrast,
      the peak voxel functional QSM (fQSM) changes in activated visual cortex ranged
      from about -10 to -30 ppb, and functional clusters were consistently smaller on
      QSM than magnitude fMRI. Mean-level DGM QSM of the time series was successfully
      extracted in all cases, while fQSM results were more prone to residual background
      fields and showed less functional change compared with standard magnitude fMRI.
      Under the conditions prescribed, standard fMRI studies may be used for robust
      mean-level DGM QSM, enabling study of DGM iron accumulation, in addition to
      functional analysis. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27687151
TI  - Exploring gender perceptions of risk of HIV infection and related behaviour among
      elderly men and women of Ga-Rankuwa, Gauteng Province, South Africa.
AB  - The literature shows that there are important differences between women and men
      in the underlying mechanisms of transmission of HIV infection and AIDS, as well
      as in the social and economic consequences of HIV/AIDS. These stem from sexual
      behaviour and socially constructed 'gender' differences between women and men in
      roles and responsibilities. Despite the fact that numerous gender-related
      sociocultural factors influence HIV/AIDS protective behaviours, little gender
      specificity is included in HIV prevention among the elderly. In order to close
      this gap, this study explored gender-related perceptions of risk of HIV infection
      among elderly men and women of Ga-Rankuwa in Gauteng Province, South Africa. This
      qualitative study used purposive sampling to conduct three focus group interviews
      with 22 women and 10 men who were above 60 years of age. Findings revealed that
      both genders blame each other for the spreading of HIV/AIDS. Male participants
      displayed the tendency to have multiple partners, whereas females accepted that
      males are promiscuous. Mixed perceptions about disclosure of HIV status were
      found. Condom use was a challenge, as men did not know how to introduce it with
      their wives, and some female participants indicated that men are resistant to
      using condoms. The elderly men also believed that women will have sex in exchange
      for money. It is concluded that there is a need for substantial behaviour change
      among both elderly males and females, which should address gender power
      relations. More in-depth and extensive research in this area is recommended.

PMID- 27687152
TI  - Qualitative evaluation of selected social factors that impact sexual risk-taking
      behaviour among African students in Kwazulu-Natal, South Africa.
AB  - BACKGROUND: The incidence of HIV and AIDS continues to be a source of great
      concern within universities in South Africa. Furthermore, university students
      constitute an important community in the intervention against the HIV/AIDS
      epidemic. Students in the age group of 15-24 years are at a greater risk of HIV
      infection than any other group in the country; yet, little is known about why
      they continue to engage in risky sexual practices. OBJECTIVES: This study was
      designed to explore the sexual behaviour of students in a metropolitan Durban
      University of Technology in KwaZulu-Natal to understand the social factors
      underlying their risk of HIV infection. METHODS: This is a qualitative study that
      used cluster sampling where the population was stratified by campus and faculty.
      The study population was selected using a standard randomization technique. This
      was a part of a multi-phased research project aimed at providing a sero
      prevalence baseline and an analysis of risk-taking behaviour at a Durban
      University of Technology in the eThekwini Metropolitan Municipality area.
      RESULTS: The study highlights peer pressure among students as an influence in
      promoting high-risk sexual behaviour. Within this context, the findings revealed
      that university students lack the ability to negotiate risk-aware decisions
      especially regarding sexual relationships. CONCLUSION: This study draws attention
      to the perspectives of African university students regarding their risk-taking
      sexual practices and selected factors which influence such behaviour. The
      findings are not exhaustive in exploring contextual antecedents that shape
      students' sexual practices. However, they provide an important basis in
      understanding key factors which expose students to HIV infections. The study
      provides insights into opportunities for further studies as well as preventative
      implications.

PMID- 27687153
TI  - Food insecurity among students living with HIV: Strengthening safety nets at the
      Nelson Mandela Metropolitan University, South Africa.
AB  - The HIV prevalence in South Africa among students at higher education
      institutions (HEIs) in 2008 was reported to be 3.4%, with the highest HIV
      prevalence found in the Eastern Cape Province. Students at these facilities are
      also increasingly affected by socio-economic constraints that may impact on food
      security. Little is known about the impact of food insecurity on HIV-infected
      students in HEIs in South Africa. The purpose of this paper is to describe food
      insecurity and the nutritional status among HIV-infected students on the Nelson
      Mandela Metropolitan University campuses in South Africa, as well as current
      initiatives to strengthen the safety nets for food-insecure students. This
      descriptive, cross-sectional survey was conducted among a convenience sample of
      known HIV-infected, registered students (n = 63), older than 18 years of age and
      managed as part of the Campus Health Service antiretroviral therapy (ART)
      programme. Ethical approval for the study was obtained from the Research Ethics
      Committee (NMMU) and participants were included in the sample after providing
      written, informed consent. Findings indicate that food insecurity was common with
      more than 60% of the sample reporting food insecurity at the household level
      during the previous month. Of the sample, 51% were classified as being either
      overweight or obese. Although food insecurity did not contribute to weight loss
      in our sample, food-insecure students were more likely to consume inadequate
      amounts of vitamins and minerals, especially antioxidants that are important in
      supporting the immune system. Food insecurity has been identified as affecting
      the majority of HIV-infected students in this study, especially regarding their
      difficulty in accessing nutritious foods. As overweight and obesity also seem to
      threaten the health and future well-being of the students, appropriate management
      of the overweight individuals and those with obesity should be instituted in
      order to prevent the development of chronic diseases of lifestyle, thus allowing
      for a healthier more productive life. Current intervention strategies to
      strengthen food security have made inroads to improve access to healthier food
      options.

PMID- 27687154
TI  - Beliefs and implementation of evidence-based practice among nurses and allied
      healthcare providers in the Valais hospital, Switzerland.
AB  - RATIONALE: Evidence-based practice (EBP) is upheld as a means for patients to
      receive the most efficient care in a given context. Despite the available
      evidence and positive beliefs about it, implementing EBP as standard daily
      practice still faces many obstacles. AIMS AND OBJECTIVES: This study investigated
      the beliefs about and implementation of EBP among nurses and allied healthcare
      providers (AHP) in 9 acute care hospitals in the canton of Valais, Switzerland.
      MATERIALS AND METHODS: A cross-sectional descriptive survey was conducted. The
      target population was composed of 1899 nurses and 126 AHPs. Beliefs about and
      implementation of EBP were measured using EBP-Beliefs and EBP-Implementation
      scales of Melnyk et al. RESULTS: The initial sample consisted in 491 participants
      (overall response rate 24.2%): 421 nurses (22.4% response rate) and 78 AHPs
      (61.9% response rate). The final sample, composed only of those who declared
      previous exposure to EBP, included 391 participants (329 nurses and 62 AHPs).
      Overall, participants had positive attitudes towards EBP and were willing to
      increase their knowledge to guide practice. However, they acknowledged poor
      implementation of EBP in daily practice. A significantly higher level of EBP
      implementation was declared by those formally trained in it (P = 0.006) and by
      those occupying more senior professional functions (P = 0.004). EBP-Belief scores
      predicted 13% of the variance in the EBP-Implementation scores (R2  = 0.13).
      DISCUSSION: EBP is poorly implemented despite positive beliefs about it.
      Continuing education and support on EBP would help to ensure that patients
      receive the best available care based on high-quality evidence, patient needs,
      clinical expertise, and a fair distribution of healthcare resources. CONCLUSION:
      This study's results will be used to guide institutional strategy to increase the
      use of EBP in daily practice.

PMID- 27687155
TI  - Ligand-dependent ribozymes.
AB  - The discovery of catalytic RNA (ribozymes) more than 30 years ago significantly
      widened the horizon of RNA-based functions in natural systems. Similarly to the
      activity of protein enzymes that are often modulated by the presence of an
      interaction partner, some examples of naturally occurring ribozymes are
      influenced by ligands that can either act as cofactors or allosteric modulators.
      Recent discoveries of new and widespread ribozyme motifs in many different
      genetic contexts point toward the existence of further ligand-dependent RNA
      catalysts. In addition to the presence of ligand-dependent ribozymes in nature,
      researchers have engineered ligand dependency into natural and artificial
      ribozymes. Because RNA functions can often be assembled in a truly modular way,
      many different systems have been obtained utilizing different ligand-sensing
      domains and ribozyme activities in diverse applications. We summarize the
      occurrence of ligand-dependent ribozymes in nature and the many examples realized
      by researchers that engineered ligand-dependent catalytic RNA motifs. We will
      also highlight methods for obtaining ligand dependency as well as discuss the
      many interesting applications of ligand-controlled catalytic RNAs. WIREs RNA
      2017, 8:e1395. doi: 10.1002/wrna.1395 For further resources related to this
      article, please visit the WIREs website.

PMID- 27687156
TI  - Measuring the representational space of music with fMRI: a case study with Sting.
AB  - Functional brain imaging has revealed much about the neuroanatomical substrates
      of higher cognition, including music, language, learning, and memory. The
      technique lends itself to studying of groups of individuals. In contrast, the
      nature of expert performance is typically studied through the examination of
      exceptional individuals using behavioral case studies and retrospective
      biography. Here, we combined fMRI and the study of an individual who is a world
      class expert musician and composer in order to better understand the neural
      underpinnings of his music perception and cognition, in particular, his mental
      representations for music. We used state of the art multivoxel pattern analysis
      (MVPA) and representational dissimilarity analysis (RDA) in a fixed set of brain
      regions to test three exploratory hypotheses with the musician Sting: (1)
      Composing would recruit neutral structures that are both unique and
      distinguishable from other creative acts, such as composing prose or visual art;
      (2) listening and imagining music would recruit similar neural regions,
      indicating that musical memory shares anatomical substrates with music listening;
      (3) the MVPA and RDA results would help us to map the representational space for
      music, revealing which musical pieces and genres are perceived to be similar in
      the musician's mental models for music. Our hypotheses were confirmed. The act of
      composing, and even of imagining elements of the composed piece separately, such
      as melody and rhythm, activated a similar cluster of brain regions, and were
      distinct from prose and visual art. Listened and imagined music showed high
      similarity, and in addition, notable similarity/dissimilarity patterns emerged
      among the various pieces used as stimuli: Muzak and Top 100/Pop songs were far
      from all other musical styles in Mahalanobis distance (Euclidean representational
      space), whereas jazz, R&B, tango and rock were comparatively close. Closer
      inspection revealed principaled explanations for the similarity clusters found,
      based on key, tempo, motif, and orchestration.

PMID- 27687158
TI  - Concordance between cardio-protective effect on isoproterenol-induced acute
      myocardial ischemia and phenolic content of different extracts of Curcuma
      aromatica.
AB  - CONTEXT: A classic traditional Chinese medicine Curcuma aromatica Salisb.
      (Zingiberaceae) has been reported to have favourable effects on the
      cardiovascular system. OBJECTIVE: To research the cardio-protective effect of
      different C. aromatica hydroalcoholic extracts on isoproterenol (ISO)-induced
      acute myocardial ischemia (AMI) in rats. The total phenols in different extracts
      were detected simultaneously. MATERIALS AND METHODS: The rhizomes of C. aromatica
      dry powder were refluxed with 30%, 50%, 70% and 90% hydroalcoholic solvents to
      obtain different extracts. Rats were pretreated with four C. aromatica extracts
      (150 mg/kg/day, i.g.) for 9 days and then given ISO (30 mg/kg/day, s.c.) for 2
      consecutive days, respectively. Heart rate, ST-segment, T-wave and serum levels
      of CK-MB, LDH, TAC, SOD, NO and MDA were measured. Total phenols of the different
      extracts were determined using the Folin-Ciocalteu assay. RESULTS: Pretreatment
      with C. aromatica significantly decreased the elevated levels of serum specific
      cardiac injury biomarkers (CK-MB and LDH), the serum level of MDA, the ST-segment
      and T-wave. In addition, C. aromatica increased the heart rate, as well as the
      levels of TAC, SOD and NO, compared to ISO-induced controls. The total phenols in
      the 70% extract were higher than in the other extracts reaching 5.629 +/- 0.037
      mg/g, crude drug. DISCUSSION AND CONCLUSION: Curcuma aromatica hydroalcoholic
      extracts exhibited remarkable cardio-protective effects against AMI in rats. The
      70% extracts showed the strongest bioactivity. These results indicate that
      ethanol concentration in preparation of extracts of C. aromatica plays an
      important role in the protective effect against AMI.

PMID- 27687157
TI  - Comparison of antibiotic regimens in preterm premature rupture of membranes:
      neonatal morbidity and 2-year follow-up of neurologic outcome.
AB  - OBJECTIVES: The objective of this study was to compare neonatal morbidity and
      neurologic outcome at 2 years between groups treated with antibiotics regimens
      consisting clarithromycin and erythromycin in preterm premature rupture of the
      membranes (pPROM) patients delivered before 32 weeks of gestation. METHODS: This
      was a retrospective study comparing neonatal morbidity as primary outcome
      measures and the neurological outcome at 2 years as secondary outcome. RESULTS: A
      total of 166 women were included: 80 treated with erythromycin and 86 treated
      with clarithromycin. The median gestational age at delivery was greater in
      clarithromycin group (p = 0.005). There was no significant difference in latency
      (p = 0.77). The incidence of histological chorioamnionitis was significantly
      lower in clarithromycin group (p = 0.004). By multivariable analysis adjusting
      confounding variables, the incidence of bronchopulmonary dysplasia and
      intraventricular hemorrhage (>=Grade 3) was lower in clarithromycin group (BPD;
      OR 0.34, 95% CI [0.13-0.90]), IVH; OR 0.23, 95% CI [0.06-0.91], respectively).
      Other morbidities and neurologic outcome at 2 years' corrected age showed no
      statistically significant difference between two groups. CONCLUSION: We suggest
      that clarithromycin-based regimen may be worth considering as an alternative
      choice of erythromycin in pPROM patients.

PMID- 27687159
TI  - Seven days in medicine: 21-27 September 2016.

PMID- 27687160
TI  - Production constraints of smallholder pig farms in agro-ecological zones of
      Mpumalanga, South Africa.
AB  - South African pig sector is a contributor to the agricultural industry. A study
      was conducted to identify the production constraints and compare the management
      practices in smallholder pig farms in Mpumalanga, South Africa. A total of 220
      selected smallholder pig farmers were interviewed. Smallholder pig farming was
      predominated by male (64 %), age above 50 years (54 %), black Africans (98.6 %),
      and three quarters of the smallholder farmers were poor to just below average.
      Majority (80 %) have no pig husbandry training, while only 33 % received
      assistance from government's Agricultural Department. In terms of stock, mixed
      breeds (89 %) from exotic pigs were mostly kept and majority (87 %) of the
      farmers kept <=10 sows in their herds. Many farmers (75 %) engaged in risky
      behavior of buying auctioned-sourced boars, free-range boars, and untested boars
      from neighbors and relatives. Few (17 %) farmers practiced vaccination and only
      10 % kept farm records. Majority of the responses on pre-weaning mortality (50 %)
      and post-weaning mortality (90 %) were within acceptable range of 1-10 and 1-5 %
      mortality rates, respectively. The lead causes of mortality were weak piglets and
      crushing (46 %), diarrhea (27 %), poor management knowledge (19 %), and
      malnutrition (16 %). Agricultural training and government incentives will
      facilitate improved productivity in smallholder pig farming.

PMID- 27687161
TI  - The chondroitin sulfate/dermatan sulfate 4-O-endosulfatase from marine bacterium
      Vibrio sp FC509 is a dimeric species: Biophysical characterization of an
      endosulfatase.
AB  - Sulfatases catalyze hydrolysis of sulfate groups. They have a key role in
      regulating the sulfation states that determine the function of several scaffold
      molecules. Currently, there are no studies of the conformational stability of
      endosulfatases. In this work, we describe the structural features and
      conformational stability of a 4-O-endosulfatase (EndoV) from a marine bacterium,
      which removes specifically the 4-O-sulfate from chondroitin sulfate/dermatan
      sulfate. For that purpose, we have used several biophysical techniques, namely,
      fluorescence, circular dichroism (CD), FTIR spectroscopy, analytical
      ultracentrifugation (AUC), differential scanning calorimetry (DSC), mass
      spectrometry (MS), dynamic light scattering (DLS) and size exclusion
      chromatography (SEC). The protein was a dimer with an elongated shape. EndoV
      acquired a native-like structure in a narrow pH range (7.0-9.0); it is within
      this range where the protein shows the maximum of enzymatic activity. The
      dimerization did not involve the presence of disulphide-bridges as suggested by
      AUC, SEC and DLS experiments in the presence of beta-mercaptoethanol (beta-ME).
      EndoV secondary structure is formed by a mixture of alpha and beta-sheet
      topology, as judged by deconvolution of CD and FTIR spectra. Thermal and chemical
      denaturations showed irreversibility and the former indicates that protein did
      not unfold completely during heating.

PMID- 27687162
TI  - Biophysical dissection of schistosome septins: Insights into oligomerization and
      membrane binding.
AB  - Septins are GTP-binding proteins that are highly conserved among eukaryotes and
      which are usually membrane-associated. They have been linked to several critical
      cellular functions such as exocytosis and ciliogenesis, but little mechanistic
      detail is known. Their assembly into filaments and membrane binding properties
      are incompletely understood and that is specially so for non-human septins where
      such information would offer therapeutic potential. In this study we use
      Schistosoma mansoni, exhibiting just four septin genes, as a simpler model for
      characterizing the septin structure and organization. We show that the
      biochemical and biophysical proprieties of its SmSEPT5 and SmSEPT10 septins are
      consistent with their human counterparts of subgroups SEPT2 and SEPT6,
      respectively. By succeeding to isolate stable constructs comprising distinct
      domains of SmSEPT5 and SmSEPT10 we were able to infer the influence of terminal
      interfaces in the oligomerization and membrane binding properties. For example,
      both proteins tended to form oligomers interacting by the N- and C-terminal
      interfaces in a nucleotide independent fashion but form heterodimers via the G
      interface, which are nucleotide dependent. Furthermore, we report for the first
      time that it is the C-terminus of SmSETP10, rather than the N-terminal polybasic
      region found in other septins, that mediates its binding to liposomes. Upon
      binding we observe formation of discrete lipo-protein clusters and higher order
      septin structures, making our system an exciting model to study interactions of
      septins with biological membranes.

PMID- 27687163
TI  - Embracing an "African Ethos" to facilitate African immigrants participation in
      medical genetics and genomics research.
AB  - BACKGROUND: Limited published research exists on perceptions and potentials for
      black African immigrants' participation in medical genetics and genomics
      research. PURPOSE: This study explores the inclination and disinclination of
      African immigrants to be involved in genetics and genomics research. METHODS: In
      depth qualitative interviews were employed in which a sample of black African
      immigrants 18 years and older (n = 34) were interviewed. DISCUSSION: Barriers
      included contrary beliefs and customs about disease and the human body that
      differs from Western conceptions, and lack of genuine connection to the health
      care system. Facilitators included promotion of an "African ethos," wherein
      Africans unite with one another in a communal extension of self and robust
      community involvement across the life span of genetic studies. CONCLUSION: It is
      important for researchers and genetic counselors to understand the sociocultural
      underpinnings of African immigrants about genetics and genomics research as an
      initial step to encouraging their participation.

PMID- 27687164
TI  - Genome-wide association studies of immune, disease and production traits in
      indigenous chicken ecotypes.
AB  - BACKGROUND: The majority of chickens in sub-Saharan Africa are indigenous
      ecotypes, well adapted to the local environment and raised in scavenging
      production systems. Although they are generally resilient to disease challenge,
      routine vaccination and biosecurity measures are rarely applied and infectious
      diseases remain a major cause of mortality and reduced productivity. Management
      and genetic improvement programmes are hampered by lack of routine data
      recording. Selective breeding based on genomic technologies may provide the means
      to enhance sustainability. In this study, we investigated the genetic
      architecture of antibody response to four major infectious diseases [infectious
      bursal disease (IBDV), Marek's disease (MDV), fowl typhoid (SG), fowl cholera
      (PM)] and resistance to Eimeria and cestode parasitism, along with two production
      traits [body weight and body condition score (BCS)] in two distinct indigenous
      Ethiopian chicken ecotypes. We conducted variance component analyses, genome-wide
      association studies, and pathway and selective sweep analyses. RESULTS: The large
      majority of birds was found to have antibody titres for all pathogens and were
      infected with both parasites, suggesting almost universal exposure. We derived
      significant moderate to high heritabilities for IBDV, MDV and PM antibody titres,
      cestodes infestation, body weight and BCS. We identified single nucleotide
      polymorphisms (SNPs) with genome-wide significance for each trait. Based on these
      associations, we identified for each trait, pathways, networks and functional
      gene clusters that include plausible candidate genes. Selective sweep analyses
      revealed a locus on chromosome 18 associated with viral antibody titres and
      resistance to Eimeria parasitism that is within a positive selection signal. We
      found no significant genetic correlations between production, immune and disease
      traits, implying that selection for altered antibody response and/or disease
      resistance will not affect production. CONCLUSIONS: We confirmed the presence of
      genetic variability and identified SNPs significantly associated with immune,
      disease and production traits in indigenous village chickens. Results underpin
      the feasibility of concomitant genetic improvement for enhanced antibody
      response, resistance to parasitism and productivity within and across indigenous
      chicken ecotypes.

PMID- 27687165
TI  - Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel
      specific modulator, in rats.
AB  - BACKGROUND: A previous study found that brain natriuretic peptide (BNP) inhibited
      inflammatory pain via activating its receptor natriuretic peptide receptor A
      (NPRA) in nociceptive sensory neurons. A recent study found that functional NPRA
      is expressed in almost all the trigeminal ganglion (TG) neurons at membrane level
      suggesting a potentially important role for BNP in migraine pathophysiology.
      METHODS: An inflammatory pain model was produced by subcutaneous injection of BmK
      I, a sodium channel-specific modulator from venom of Chinese scorpion Buthus
      martensi Karsch. Quantitative PCR, Western Blot, and immunohistochemistry were
      used to detect mRNA and protein expression of BNP and NPRA in dorsal root
      ganglion (DRG) and dorsal horn of spinal cord. Whole-cell patch clamping
      experiments were conducted to record large-conductance Ca2+-activated K+ (BKCa)
      currents of membrane excitability of DRG neurons. Spontaneous and evoked pain
      behaviors were examined. RESULTS: The mRNA and protein expression of BNP and NPRA
      was up-regulated in DRG and dorsal horn of spinal cord after BmK I injection. The
      BNP and NPRA was preferentially expressed in small-sized DRG neurons among which
      BNP was expressed in both CGRP-positive and IB4-positive neurons while NPRA was
      preferentially expressed in CGRP-positive neurons. BNP increased the open
      probability of BKCa channels and suppressed the membrane excitability of small
      sized DRG neurons. Intrathecal injection of BNP significantly inhibited BmK
      induced pain behaviors including both spontaneous and evoked pain behaviors.
      CONCLUSIONS: These results suggested that BNP might play an important role as an
      endogenous pain reliever in BmK I-induced inflammatory pain condition. It is also
      suggested that BNP might play a similar role in other pathophysiological pain
      conditions including migraine.

PMID- 27687166
TI  - Radial Head Subluxation: Factors Associated with Its Recurrence and Radiographic
      Evaluation in a Tertiary Pediatric Emergency Department.
AB  - BACKGROUND: Radial head subluxation (RHS) is a common complaint seen in the
      pediatric emergency department in children ages 6 months to 4 years. Classically,
      injury occurs due to axial traction on the arm, but this mechanism is not
      universal. Some patients will have recurrent RHS; some may undergo x-ray (XR)
      evaluation for alternative diagnosis. OBJECTIVES: To determine factors associated
      with recurrences and radiographic evaluations in RHS. METHODS: A retrospective
      study with inclusion criteria: under 10 years of age with discharge diagnosis
      "nursemaid," "radial head," or "subluxation." We examined factors associated with
      RHS recurrences, circumstances when radiographic evaluations performed,
      physician's training background (pediatric vs. general emergency medicine),
      mechanisms of injury, and demographic factors including age, gender, and arm
      involved. RESULTS: In 246 visits, median age was 27 months (interquartile range
      16.1), with females comprising 55.7% (n = 137), and left-sided predominance (52%,
      n = 130). Mechanisms of injury were classified as "pull" (65.9%, n = 162), "non
      pull" (15.9%, n = 39), and "unknown" (18.3%, n = 45). Eighteen patients with
      recurring RHS were more likely to be male (p = 0.008). In 61 visits where
      radiography was performed, patients were older (p = 0.03), with a higher
      frequency seen in non-pull and unknown mechanism (p = 0.0001). No significant
      difference was found in frequency of radiographs obtained in regard to physician
      training (p = 0.4660). CONCLUSION: RHS can result from a myriad of mechanisms. We
      found that recurrence was more likely in male patients. Factors associated with
      radiographic evaluation included atypical mechanism, older age, and unclear
      history, regardless of physician training background.

PMID- 27687167
TI  - Psychiatric Emergencies for Clinicians: Emergency Department Management of
      Benzodiazepine Withdrawal.

PMID- 27687168
TI  - Effect of a Multi-Diagnosis Observation Unit on Emergency Department Length of
      Stay and Inpatient Admission Rate at Two Canadian Hospitals.
AB  - BACKGROUND: Observation units (OUs) have been shown to reduce emergency
      department (ED) lengths of stay (LOS) and admissions. Most published studies have
      been on OUs managing single complaints. OBJECTIVE: Our aim was to determine
      whether an OU reduces ED LOS and hospital admission rates for adults with a
      variety of presenting complaints. METHODS: We comparatively evaluated two
      hospitals in British Columbia, Canada (hereafter ED A and ED B) using a pre-post
      design. Data were extracted from administrative databases. The post-OU cohort
      included all adults presenting 6 months after OU implementation. The pre-OU
      cohort included all adults presenting in the same 6-month period 1 year before OU
      implementation. RESULTS: There were 109,625 patient visits during the study
      period. Of the 56,832 visits during the post-OU period (27,512 to ED A and 29,318
      to ED B), 1.9% were managed in the OU in ED A and 1.4% in ED B. Implementation
      was associated with an increase in the median ED LOS at ED A (179.0 min pre vs.
      192.0 min post [+13.0 min]; p < 0.001; mean difference -12.5 min, 95% confidence
      interval [CI] -15.2 to -9.9 min), but no change at ED B (182.0 min pre vs. 182.0
      min post; p = 0.55; mean difference +2.0 min, 95% CI -0.7 to +4.7 min).
      Implementation significantly decreased the hospital admission rate for ED A
      (17.8% pre to 17.0% post [-0.8%], 95% CI -0.18% to 0.15%; p < 0.05) and did not
      significantly change the hospital admission rate at ED B (18.9% pre to 18.3% post
      [-0.6%], 95% CI -1.19% to -0.09%; p = 0.09). CONCLUSIONS: A multi-diagnosis OU
      can reduce hospital admission rate in a site-specific manner. In contrast to
      previous studies, we did not find that an OU reduced ED LOS. Further research is
      needed to determine whether OUs can reduce ED overcrowding.

PMID- 27687169
TI  - Influenza in the Emergency Department: Vaccination, Diagnosis, and Treatment.

PMID- 27687170
TI  - Catamenial Epilepsy: The Menstrual Cycle as a Clue to Predict Future Refractory
      Seizures.
AB  - BACKGROUND: Catamenial epilepsy is defined as an increase in the frequency of
      seizures during a particular phase of the menstrual cycle. The increased seizure
      frequency is attributed to the cyclic variation and neuroactive properties of
      endogenous steroid hormones. It is estimated that more than one-third of women
      with epilepsy experience catamenial seizure exacerbation. CASE REPORT: We present
      the case of a young female patient who presented to the emergency department with
      an increase in seizure frequency that coincided with her menstrual cycle, despite
      complete medication compliance. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
      THIS?: It is important for the emergency physician to consider catamenial
      epilepsy in the differential diagnosis for secondary causes of seizure to ensure
      appropriate follow-up, as well as improve the quality of life of patients
      suffering from uncontrolled seizures.

PMID- 27687171
TI  - Emergent Needle Aspiration of an Orbital Subperiosteal Hematoma.
AB  - BACKGROUND: Delayed presentation of orbital trauma as an acute subperiosteal
      hematoma. CASE REPORT: A 12-year-boy developed sudden painful abaxial proptosis
      of the left eyeball 15 days after blunt trauma over the forehead. On contrast
      enhanced computed tomography, a heterogeneous, hypodense, non-enhancing mass with
      biconvex contour was seen adjacent to the orbital roof. Direct needle drainage
      was performed and about 10 mL dark blood was aspirated. Proptosis reduced
      immediately and resolved completely at 2 weeks follow-up. WHY SHOULD AN EMERGENCY
      PHYSICIAN BE AWARE OF THIS?: Sudden proptosis with no immediate history of trauma
      can be alarming for the emergency physician. Familiarity with this clinical
      entity and early drainage can decrease morbidity.

PMID- 27687172
TI  - Malpractice Litigation and Testicular Torsion in the Spanish Setting: Lessons to
      Learn.

PMID- 27687173
TI  - Airway Management of a Patient with an Acute Floor of the Mouth Hematoma after
      Dental Implant Surgery in the Lower Jaw.
AB  - BACKGROUND: Over the last decades, dental implants have become increasingly
      popular in the prosthetic rehabilitation of patients. This has subsequently led
      to an increase of perioperative complications. Obstruction of the airway as a
      result of a floor of mouth hematoma after dental implant surgery is a rare but
      life-threatening complication. CASE REPORT: A 62-year-old man presented to the
      emergency department with a compromised airway caused by a hematoma in the floor
      of the mouth that occurred during dental implant surgery in the edentulous
      anterior mandible. Computed tomography angiography images revealed an elevation
      of the floor of mouth with subsequent occlusion of the airway. In addition, a
      perforation of the lingual mandibular cortical plate was observed that was caused
      by two malpositioned dental implants. Awake fiberoptic intubation was immediately
      performed, the two malpositioned dental implants were subsequently removed, and
      the patient was extubated after 3 days. WHY SHOULD AN EMERGENCY PHYSICIAN BE
      AWARE OF THIS?: Perforation of the lingual mandibular cortical plate during
      dental implant surgery can lead to life-threatening bleeding in the floor of the
      mouth. This condition can be successfully treated by awake fiberoptic intubation
      and, if necessary, the malpositioned dental implants can be subsequently removed.

PMID- 27687174
TI  - Delayed Antitoxin Treatment of Two Adult Patients with Botulism after Cosmetic
      Injection of Botulinum Type A Toxin.
AB  - BACKGROUND: Injection of botulinum toxin type A for cosmetic purposes is common.
      It is believed to be safe, but adverse reactions have been reported, including
      dysphagia, generalized paralysis, respiratory depression, and death caused by
      focal injection of the toxin. Early administration of antitoxin in patients with
      adverse reactions is the mainstay of management, but the time window for its
      clinical efficacy is not well defined. CASE REPORTS: Two female adult patients
      with clinical botulism after botulinum toxin type A injection are described. Both
      patients had received intramuscular injection of botulinum toxin type A in their
      calves at beauty shops for cosmetic reasons. They developed clinical botulism
      about 3 days postinjection. They presented late to the emergency department.
      Monovalent type A botulinum antitoxin was administered 7 and 9 days from symptom
      onset, respectively. Both patients showed clinical improvement after the
      antitoxin treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?:
      Patients may present to the emergency department with systemic effects of
      botulinum toxin type A after cosmetic injection. Clinical efficacy of botulinum
      antitoxin treatment was observed in two patients who were given the drug 7 and 9
      days after the occurrence of symptoms of botulism after cosmetic injection of
      botulinum toxin type A. It may be worthwhile to commence antitoxin treatment even
      if patients present late.

PMID- 27687176
TI  - The role of patelloplasty in total knee arthroplasty.
AB  - INTRODUCTION: Anterior knee pain (AKP) is a frequent complication after total
      knee arthroplasty (TKA). Patelloplasty, defined as reshaping the patella for
      optimal tracking in the trochlea, has been proposed to reduce the rate of this
      complication in patellar retaining implants. Aim of this study was to analyze the
      available literature regarding the outcomes of patelloplasty and to assess its
      methodological quality. MATERIALS AND METHODS: A comprehensive review of the
      English literature was performed using the keywords "total knee arthroplasty",
      "patelloplasty" and "patellaplasty" with no limit regarding the year of
      publication. All the selected articles were evaluated with the Coleman score.
      RESULTS: Seven full text articles were retrieved. The initial cohort included 461
      knees in the study groups and 465 in the control groups. At an average FU of 70.6
      months 447 knees were reviewed in the study group and 447 in the control groups.
      The global rate of AKP after patelloplasty was 11.3 % which compared to 7.9 % in
      the patella resurfacing control group. No signs of specific patellar
      complications due to patelloplasty were reported. Average Coleman score was 66.9.
      CONCLUSION: Most of the literature has barely sufficient methodological quality.
      Patelloplasty aims at reducing patellar thickness and improve its tracking with
      TKA. This procedure is a safe and easy option with no reported adverse effects.
      In the included studies, outcome seemed to be superior in comparison with
      isolated osteophyte removal and denervation with a lower rate of AKP. The
      included studies, however, report a lower rate of AKP following TKA with patellar
      resurfacing. Patelloplasty may have the potential to improve the outcome of
      patellar retaining implants. LEVEL OF EVIDENCE: 4, systematic review.

PMID- 27687175
TI  - DNA damage responses and stress resistance: Concepts from bacterial SOS to
      metazoan immunity.
AB  - The critical need for species preservation has driven the evolution of mechanisms
      that integrate stress signals from both exogenous and endogenous sources. Past
      research has been largely focused on cell-autonomous stress responses; however,
      recently their systemic outcomes within an organism and their implications at the
      ecological and species levels have emerged. Maintenance of species depends on the
      high fidelity transmission of the genome over infinite generations; thus, many
      pathways exist to monitor and restore the integrity of the genome and to
      coordinate DNA repair with other cellular processes, such as cell division and
      growth. The specifics of these DNA damage responses (DDRs) vary vastly but some
      general themes are conserved from ancient organisms, such as bacteria and
      archaea, to humans. Despite decades of research, however, DDRs still have many
      layers of complexity and some surprises left to be discovered. One of the most
      interesting current research topics is the link between DNA damage and stress
      resistance: the outcomes of DDRs can protect the organism from other secondary
      challenges. At this time, these types of responses are best characterized in
      bacteria and the simple metazoan model, Caenorhabditis elegans, but it is
      becoming clear that similar processes also exist in higher organisms.

PMID- 27687177
TI  - Safety of simultaneous bilateral total knee arthroplasty using an extramedullary
      referencing system: results from 2098 consecutive patients.
AB  - INTRODUCTION: Simultaneous bilateral total knee arthroplasty (TKA) has been
      associated with a high risk of morbidity and mortality. The orthopedic surgeon
      must, therefore, decide whether bilateral simultaneous TKA is a safe operation to
      perform and endeavor to decrease the risk of serious complications or even death.
      METHODS: This retrospective review included 2098 consecutive patients who
      underwent bilateral simultaneous TKAs by the protocol used in our institution,
      including the use of extramedullary instruments to minimize medullary canal
      invasion and overlapping procedures for both knees to decrease operation time.
      RESULTS: The incidence rate of occurred complications was 0.33 % for symptomatic
      pulmonary embolism, 0.62 % for deep surgical infection requiring revision
      surgery, 0.05 % for 14-day mortality, 1.14 % for adverse cardiac events, and 0.76
      % for postsurgical delirium within the 1-year follow-up. CONCLUSIONS: Our
      protocols, including the use of an extramedullary referencing system and
      overlapping procedures for both knees, may be considered to decrease the
      perioperative short-term morbidity and 14-day mortality rates in simultaneous
      bilateral TKA.

PMID- 27687178
TI  - Letter to the Editor re: Biglari et al. (2016).

PMID- 27687180
TI  - Editors' Note.

PMID- 27687181
TI  - Methods in Biological Oxidative Stress: K. Hensley and R.A. Floyd (Eds), 2003.
      Humana Press, New Jersey.

PMID- 27687179
TI  - [Principles of plastic pediatric surgery: Thirty years of surgical practice].
AB  - In this document, Pr Guy Magalon presents a reflection on the plastic pediatric
      surgery drawn from 30 years of surgical practice. His thinking is supported by
      several examples of plastic surgery results from children reviewed in adulthood.
      These cases highlight the evolution of surgical practices and the need for
      continuing education for surgeons to adapt to technical progress. Professor
      Magalon honors his masters and shares his personal vision of the principles of
      pediatric plastic surgery.

PMID- 27687182
TI  - The Antioxidant Vitamins C and E: Packer L, Traber MG, Kramer K and Frei B. (Eds)
      AOCS Press, Champaign, Illinois, 2002.

PMID- 27687183
TI  - Multitemporal analysis of forest fragmentation in Hindu Kush Himalaya-a case
      study from Khangchendzonga Biosphere Reserve, Sikkim, India.
AB  - Forests in the mountains are a treasure trove; harbour a large biodiversity; and
      provide fodder, firewood, timber and non-timber forest products; all of these are
      essential for human survival in the highest mountains on earth. The present paper
      attempts a spatiotemporal assessment of forest fragmentation and changes in land
      use land cover (LULC) pattern using multitemporal satellite data over a time span
      of around a decade (2000-2009), within the third highest protected area (PA) in
      the world. The fragmentation analysis using Landscape Fragmentation Tool (LFT)
      depicts a decrease in large core, edge and patches areas by 5.93, 3.64 and 0.66
      %, respectively, while an increase in non-forest and perforated areas by 6.59 and
      4.01 %, respectively. The land cover dynamics shows a decrease in open forest,
      alpine scrub, alpine meadows, snow and hill shadow areas by 2.81, 0.39, 8.18,
      3.46 and 0.60 %, respectively, and there is an increase in dense forest and
      glacier area by 4.79 and 10.65 %, respectively. The change analysis shows a major
      transformation in areas from open forest to dense forest and from alpine meadows
      to alpine scrub. In order to quantify changes induced by forest fragmentation and
      to characterize composition and configuration of LULC mosaics, fragmentation
      indices were computed using Fragstats at class level, showing the signs of
      accelerated fragmentation. The outcome of the analysis revealed the effectiveness
      of geospatial tools coupled with landscape ecology in characterization and
      quantification of forest fragmentation and land cover changes. The present study
      provides a baseline database for sustainable conservation planning that will
      benefit the subsistence livelihoods in the region. Recommendations made based on
      the present analysis will help to recover forest and halt the pessimistic effects
      of fragmentation and land cover changes on biodiversity and ecosystem services in
      the region.

PMID- 27687184
TI  - The effects of soil liming and sewage sludge application on dynamics of copper
      fractions and total copper concentration.
AB  - The paper deals with effects of liming and different doses of municipal sewage
      sludge (5, 10, and 15 % of soil mass) on copper speciation in soil. In all
      samples, pH was determined together with total copper concentration, which was
      measured with the ICP-AES method. Concentration of copper chemical fractions was
      determined using the seven-step procedure of Zeien and Brummer. In the soil
      treated with the highest dose of sludge (15 %), there was, compared to the
      control, a twofold increase in the concentration of copper and a threefold
      increase in the concentration of nitrogen. Copper speciation analysis showed that
      in the municipal sewage sludge the easily soluble and exchangeable fractions (F1
      and F2) constituted only a small share of copper with the highest amount of this
      metal in the organic (F4) and residual (F7) fractions. In the soil, at the
      beginning of the experiment, the highest share was in the organic fraction (F4),
      the residual fraction (F7) but also in the fraction where copper is bound to
      amorphous iron oxides (F5). After 420 days, at the end of the experiment, the
      highest amount of copper was mainly in the organic fraction (F4) and in the
      fraction with amorphous iron oxides (F5). Due to mineralization of organic matter
      in the sewage sludge, copper was released into the soil with the share of the
      residual fraction (F7) decreasing. In this fraction, there was much more copper
      in limed soil than in non-limed soil.

PMID- 27687185
TI  - Diffusive gradients in thin films measurement of sulfur stable isotope variations
      in labile soil sulfate.
AB  - A diffusive gradient in thin films (DGT) technique, based on a strongly basic
      anion exchange resin (Amberlite IRA-400), was successfully tested for 34S/32S
      analysis in labile soil sulfate. Separation of matrix elements (Na, K, and Ca)
      that potentially cause non-spectral interferences in 34S/32S analysis by MC ICP
      MS (multi-collector inductively coupled plasma-mass spectrometry) during sampling
      of sulfate was demonstrated. No isotopic fractionation caused by diffusion or
      elution of sulfate was observed below a resin gel disc loading of <=79 MUg S.
      Above this threshold, fractionation towards 34S was observed. The method was
      applied to 11 different topsoils and one mineral soil profile (0-100 cm depth)
      and compared with soil sulfate extraction by water. The S amount and isotopic
      ratio in DGT-S and water-extractable sulfate correlated significantly (r 2 = 0.89
      and r 2 = 0.74 for the 11 topsoils, respectively). The systematically lower
      34S/32S isotope ratios of the DGT-S were ascribed to mineralization of organic S.

PMID- 27687186
TI  - High-throughput and sensitive analysis of urinary heterocyclic aromatic amines
      using isotope-dilution liquid chromatography-tandem mass spectrometry and robotic
      sample preparation system.
AB  - Heterocyclic aromatic amines (HCAA) are listed by the US Food and Drug
      Administration (FDA) as harmful or potentially harmful constituents of tobacco
      smoke. However, quantifying HCAA exposure is challenging. In this study, we
      developed a sensitive, precise, and accurate isotope dilution, liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify urinary
      HCAAs in smokers and nonsmokers. The high-throughput robotic sample preparation
      system could handle a throughput of over 300 samples per day, while maintaining
      intra-day and inter-day imprecision and bias <=10 %. The limits of detection of
      carcinogenic HCAAs ranged from 0.31 to 0.83 pg/mL. The validated method was
      applied to measure HCAAs in urine collected from smokers and non-smokers. This
      sensitive and efficient analytical method is ideal to support large-scale
      biomonitoring studies of HCAA exposure. Graphical Abstract LC/MS/MS and robotic
      sample preparation system for urinary HCAA analysis.

PMID- 27687187
TI  - The strategy of repeat stereotactic radiosurgery without whole brain radiation
      treatment for new brain metastases: Outcomes and implications for follow-up
      monitoring.
AB  - PURPOSE: Stereotactic radiosurgery (SRS) is widely used to treat brain metastases
      in place of whole brain radiation therapy (WBRT), with the goal of reducing
      treatment toxicity balanced against the risk of developing new metastases. We
      evaluated outcomes of repeated courses of SRS in the management of new brain
      metastases as an alternative to salvage WBRT. METHODS AND MATERIALS: We conducted
      a single-institution retrospective review of 239 patients treated with SRS
      without WBRT for brain metastases from 2004 to 2014. Eighty-six patients received
      at least 2 courses of SRS for new brain metastases. Outcome metrics included
      survival, development of symptomatic new brain metastases, neurologic symptoms at
      death or last follow-up, and ultimate WBRT. RESULTS: Eighty-six patients (median
      age, 59 years) underwent a median of 2 courses of SRS (range, 2-6), with a median
      of 2 lesions treated initially and on retreatment. The median interval between
      SRS treatments was 5.8 months (range, 1.2-69.1). New brain metastases after
      initial radiosurgery were detected by routine imaging in 87% of cases. Median
      overall survival from repeat SRS was 13.0 months (range, 0.3-64.5) and from
      initial brain metastasis diagnosis 25.0 months (range, 2.0-68.1). On multivariate
      analysis, Eastern Cooperative Oncology Group performance status 0-1 (hazard ratio
      [HR], 0.37; 95% confidence interval [CI], 0.15-0.90; P=.029), controlled
      extracranial disease (HR, 0.35; 95% CI, 0.13-0.94; P=.038), and interval between
      initial and second SRS >6 months (HR, 0.49; 95% CI, 0.25-0.96; P=.037) correlated
      with improved overall survival from brain metastasis diagnosis. A total of 24.7%
      of patients had symptomatic intracranial metastatic disease at death or last
      follow-up, and 26.7% ultimately received WBRT. CONCLUSION: Repeated SRS is a
      reasonable option for patients with new brain metastases, as our results suggest
      favorable survival outcomes with this approach. New lesions infrequently caused
      neurologic symptoms before routine imaging detection, and a minority of patients
      had symptomatic intracranial disease at death or last follow-up.

PMID- 27687188
TI  - The American Board of Radiology radiation oncology Maintenance of Certification
      Part 3 Modular Examination: Evaluation of the first administration.
AB  - Based on data obtained from clinical practice analysis (CPA) surveys performed in
      2010 and 2013, and with input from its maintenance of certification (MOC)
      advisory committee, the American Board of Radiology (ABR) recognized that the
      changing nature of radiation oncology practice patterns warranted revisions of
      its MOC Part III cognitive examination. One significant revision was the
      introduction of a modular examination that allowed diplomates to select specific
      areas of clinical interest. The module-based items represented 30% (60 of 200) of
      total examination content. The new modular examination was administered for the
      first time in October 2015. Logistics of examination development, administration,
      and diplomate post-examination survey responses are reviewed.

PMID- 27687189
TI  - Delineation of radiation therapy target volumes for cutaneous malignancies
      involving the ophthalmic nerve (cranial nerve V-1) pathway.
AB  - PURPOSE: The ophthalmic nerve (cranial nerve V-1) runs in close proximity to the
      globe, optic nerve, chiasm, and brain. The purpose of this study was to provide
      contouring guidance using computed tomography (CT)-identifiable landmarks, based
      on an analysis of skin cancer patients with V-1 invasion. METHODS AND MATERIALS:
      Radiation oncology planning CT scans were analyzed for landmarks to guide V-1
      target delineation from the skin surface to the trigeminal ganglion. Axial and
      coronal magnetic resonance imaging (MRI) sequences were fused with the planning
      CT to confirm soft-tissue findings and identify enhancement related to perineural
      spread. CT/MRI-based anatomic landmarks were catalogued and described on an
      atlas. RESULTS: Soft-tissue and bony landmarks were confirmed as consistently
      identifiable on CT with assistance from fused MRI. A reference atlas was
      developed that shows the entirety of the V-1 pathway on consecutive CT slices.
      CONCLUSIONS: Initial delineation of the V-1 pathway can be accomplished using CT
      visualized landmarks confirmed on fused MRI. This CT/MRI atlas will assist
      radiation oncologists in delineation of the V-1 pathway.

PMID- 27687190
TI  - Mitral Regurgitation in Patients With Hypertrophic Obstructive Cardiomyopathy:
      Implications for Concomitant Valve Procedures.
AB  - BACKGROUND: Incidence and outcome of mitral valve (MV) surgery are unknown in
      patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing extended
      transaortic septal myectomy. OBJECTIVES: This study sought to define indications
      and suitable operative strategy for mitral regurgitation (MR) in patients with
      HOCM. METHODS: A total of 2,107 septal myectomy operations performed in adults
      from January 1993 to May 2014 at Mayo Clinic in Rochester, Minnesota, were
      retrospectively reviewed. Patients with prior MV operation and apical
      hypertrophic cardiomyopathy were excluded. Overall, 2,004 operations were
      performed in 1,993 patients. RESULTS: Pre-operative MR was grade >=3 (of 4) in
      1,152 operations (57.5%). Systolic anterior motion of mitral leaflets caused the
      MR in most patients. However, intrinsic MV disease was identified pre-operatively
      in 99 patients, all of whom had MV surgery (with septal myectomy). In 1,905
      operations, no intrinsic MV disease was identified pre-operatively; in 1,830
      (96.1%), septal myectomy was performed without a direct MV procedure. For 75
      patients, intrinsic MV disease discovered intraoperatively led to concomitant MV
      repair (86.7%) or replacement (13.3%). After isolated septal myectomy, the
      percentage of patients with MR grade >=3 decreased from 54.3% to 1.7% (p = 0.001)
      on early post-operative echocardiography. Among 174 patients with concomitant MV
      surgery, late survival was superior with MV repair (n = 133 [76.4%]) versus
      replacement (10-year survival: 80.0% vs. 55.2%; p = 0.002). CONCLUSIONS: In most
      patients with HOCM, MR related to systolic anterior motion of the MV is relieved
      through adequate myectomy. Concomitant MV surgery is rarely necessary unless
      intrinsic MV disease is present. When MV procedures are required, repair is
      preferred because of improved survival compared with replacement.

PMID- 27687191
TI  - MV Surgery as Adjunct to Surgical Myectomy for Obstructive HCM: Less Is More Than
      Enough.

PMID- 27687193
TI  - Time to Retire the BMI?: Evaluating Abdominal Adipose Tissue Imaging as Novel
      Cardiovascular Risk Biomarker.

PMID- 27687192
TI  - Association of Changes in Abdominal Fat Quantity and Quality With Incident
      Cardiovascular Disease Risk Factors.
AB  - BACKGROUND: Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)
      are associated with adverse cardiometabolic risk profiles. OBJECTIVES: This study
      explored the degree to which changes in abdominal fat quantity and quality are
      associated with changes in cardiovascular disease (CVD) risk factors. METHODS:
      Study participants (n = 1,106; 44.1% women; mean baseline age 45.1 years) were
      drawn from the Framingham Heart Study Third Generation cohort who participated in
      the computed tomography (CT) substudy Exams 1 and 2. Participants were followed
      for 6.1 years on average. Abdominal adipose tissue volume in cm(3) and
      attenuation in Hounsfield units (HU) were determined by CT-acquired abdominal
      scans. RESULTS: The mean fat volume change was an increase of 602 cm(3) for SAT
      and an increase of 703 cm(3) for VAT; the mean fat attenuation change was a
      decrease of 5.5 HU for SAT and an increase of 0.07 HU for VAT. An increase in fat
      volume and decrease in fat attenuation were associated with adverse changes in
      CVD risk factors. An additional 500 cm(3) increase in fat volume was associated
      with incident hypertension (odds ratio [OR]: 1.21 for SAT; OR: 1.30 for VAT),
      hypertriglyceridemia (OR: 1.15 for SAT; OR: 1.56 for VAT), and metabolic syndrome
      (OR: 1.43 for SAT; OR: 1.82 for VAT; all p < 0.05). Similar trends were observed
      for each additional 5 HU decrease in abdominal adipose tissue attenuation. Most
      associations remained significant even after further accounting for body mass
      index change, waist circumference change, or respective abdominal adipose tissue
      volumes. CONCLUSIONS: Increasing accumulation of fat quantity and decreasing fat
      attenuation are associated with worsening of CVD risk factors beyond the
      associations with generalized adiposity, central adiposity, or respective adipose
      tissue volumes.

PMID- 27687194
TI  - Transcatheter Pulmonary Valve Replacement Reduces Tricuspid Regurgitation in
      Patients With Right Ventricular Volume/Pressure Overload.
AB  - BACKGROUND: Tricuspid regurgitation (TR) is a common and important comorbidity in
      patients with postoperative right ventricular outflow tract (RVOT) obstruction or
      pulmonary regurgitation (PR). Transcatheter pulmonary valve replacement (TPVR)
      has become a useful tool in the management of postoperative RVOT obstruction and
      PR, but it is unknown whether relief of the right ventricular volume and/or
      pressure overload by TPVR will have a beneficial effect on TR, as is often seen
      with surgical pulmonary valve replacement. OBJECTIVES: This study sought to
      assess the prevalence of and factors associated with significant TR in patients
      undergoing TPVR for RVOT obstruction or PR. METHODS: Data were combined from 3
      prospective multicenter trials of patients referred for TPVR. Follow-up data
      through 5 years post-implantation were analyzed. RESULTS: Of 300 patients
      studied, 77 (25.6%) had moderate or severe TR at baseline. After TPVR, TR
      severity was improved in 65% of those patients, and more than one-half had mild
      TR or less TR at discharge. Of 13 patients with severe TR pre-implantation, only
      1 had severe TR at 1-year follow-up and beyond. Moderate or severe baseline TR
      was associated with shorter freedom from RVOT reintervention after TPVR.
      CONCLUSIONS: In this prospective multicenter study of post-operative patients
      with RVOT obstruction and/or PR, TR was common. In patients with significant
      baseline TR, TPVR resulted in clinically relevant acute reductions in TR that
      persisted over at least 5 years of follow-up. These observations support the
      application of TPVR therapy in patients with RVOT obstruction or PR who are
      anatomically suitable, even in the setting of significant concomitant TR.

PMID- 27687195
TI  - Fate and Management of Tricuspid Regurgitation Following Transcatheter Pulmonary
      Valve Replacement.

PMID- 27687196
TI  - Cardiac Recovery During Long-Term Left Ventricular Assist Device Support.
AB  - BACKGROUND: The number of centers with left ventricular assist device (LVAD)
      research programs focused on cardiac recovery is very small. Therefore, this
      phenomenon has been reported in real-world multi-center registries as a rare
      event. OBJECTIVES: This study evaluated the incidence of cardiac recovery with an
      a priori LVAD implantation strategy of bridge-to-recovery (BTR) and constructed a
      recovery predictive model. METHODS: The study included LVAD recipients registered
      in the Interagency Registry for Mechanically Assisted Circulatory Support
      (INTERMACS). Cardiac recovery was evaluated in BTR and non-BTR patients. A
      weighted score was derived and externally validated in patients of the Utah
      Cardiac Recovery (UCAR) program. RESULTS: Of 15,138 INTERMACS patients, cardiac
      recovery occurred in 192 (1.3%). The incidence of recovery was 11.2% (n = 14) in
      BTR compared with 1.2% (n = 178) in non-BTR patients (p < 0.0001). Independent
      predictors of recovery included: age <50 years, non-ischemic cardiomyopathy, time
      from cardiac diagnosis <2 years, absence of ICD, creatinine <=1.2 mg/dl, and
      LVEDD <6.5 cm (c-index: 0.85; p < 0.0001). A weighted score termed I-CARS,
      effectively stratified patients based on their probability of recovery. I-CARS
      was validated in the UCAR cohort (n = 190) with good performance (AUC: 0.94; 95%
      CI: 0.91 to 0.98). One-year survival after LVAD explantation, available in
      INTERMACS for 21 (11%) patients, was 86%. CONCLUSIONS: The incidence of cardiac
      recovery is higher in patients implanted with an a priori BTR strategy. We
      developed a simple tool to help identify patients in whom recovery is feasible.
      In BTR patients with favorable characteristics, I-CARS suggests a 24% probability
      of successful LVAD explantation. Large-scale studies to better address post
      explantation outcomes are warranted.

PMID- 27687197
TI  - Another Grain in the Search for the True Rate of Myocardial Recovery.

PMID- 27687199
TI  - Feed My Heart or Eat It: miR-22 Decides.

PMID- 27687198
TI  - Preclinical Development of a MicroRNA-Based Therapy for Elderly Patients With
      Myocardial Infarction.
AB  - BACKGROUND: Aging populations show higher incidences of myocardial infarction
      (MI) and heart failure (HF). Cardiac remodeling post-MI leads to progressive
      impaired cardiac function caused by a disarray of several processes including
      derailed autophagy. Microribonucleic acids (miRNAs) are known to be key players
      in cardiovascular disease but their involvement in cardiac autophagy and aging is
      not well understood. OBJECTIVES: This study sought to identify new miRNA
      candidates that regulate cardiac autophagy and aging. METHODS: We exploited a
      high-throughput, fluorescence-activated cell sorting-based green fluorescent
      protein-LC3 detection method to measure the autophagic flux in cardiomyocytes
      after transfection of a precursor miRNA library consisting of 380 miRNAs. This
      was followed by a series of molecular and in vivo studies. RESULTS: Together with
      additional expression screenings, we identified miR-22 as an abundant and strong
      inhibitor of the cardiac autophagy process. Cardiac miR-22 expression levels
      increased during aging of mice as well as in aging neonatal cardiomyocytes in
      vitro by a P53-dependent mechanism. Inhibition of miR-22 in aging cardiomyocytes
      in vitro activated autophagy and inhibited cellular hypertrophy. Pharmacological
      inhibition of miR-22 post-MI in older mice activated cardiac autophagy, prevented
      post-infarction remodeling, and improved cardiac function compared with control
      subjects. Interestingly, similar effects were less pronounced in younger mice
      with significantly lower cardiac miR-22 expression levels. In addition,
      circulating levels of miR-22 in 154 patients with systolic HF were highly
      associated with early mortality. CONCLUSIONS: We concluded that miR-22 is an
      important regulator of cardiac autophagy and a potential therapeutic target,
      especially in the older myocardium. Finally, circulating miR-22 provides
      prognostic information for HF patients, highlighting miR-22 as a promising
      therapeutic and biomarker candidate for cardiovascular disorders.

PMID- 27687200
TI  - Hyperkalemia in Heart Failure.
AB  - Disorders of potassium homeostasis can potentiate the already elevated risk of
      arrhythmia in heart failure. Heart failure patients have a high prevalence of
      chronic kidney disease, which further heightens the risk of hyperkalemia,
      especially when renin-angiotensin-aldosterone system inhibitors are used. Acute
      treatment for hyperkalemia may not be tolerated in the long term. Recent data for
      patiromer and sodium zirconium cyclosilicate, used to treat and prevent high
      serum potassium levels on a more chronic basis, have sparked interest in the
      treatment of hyperkalemia, as well as the potential use of renin-angiotensin
      aldosterone system inhibitors in patients who were previously unable to take
      these drugs or tolerated only low doses. This review discusses the epidemiology,
      pathophysiology, and outcomes of hyperkalemia in heart failure; provides an
      overview of traditional and novel ways to approach management of hyperkalemia;
      and discusses the need for further research to optimally treat heart failure.

PMID- 27687201
TI  - Implantable Electronic Cardiac Devices and Compatibility With Magnetic Resonance
      Imaging.
AB  - There is a growing population of patients with implanted electronic cardiac
      devices and a concomitant increase in the use of magnetic resonance (MR). There
      are theoretical safety risks posed to such devices by MR. However, there are now
      considerable laboratory data and clinical experience demonstrating safety in this
      setting, assuming appropriate device selection and patient monitoring. Herein, we
      review these data and our safety protocol and the new generation of devices that
      have been prospectively designed and tested to be safe for MR scanning, assuming
      certain conditions are met (i.e., devices that are MR-conditional). We also argue
      that the available data do not support a complete transition to implantation of
      MR-conditional devices.

PMID- 27687202
TI  - Cardiometabolic Disease Is Prevalent in Normal-Weight Chinese Adults.

PMID- 27687203
TI  - Bypass Surgery Versus Endovascular Therapy in Chronic Hemodialysis Patients With
      CLI Due to Infrainguinal Disease.

PMID- 27687204
TI  - Primum Non Nocere: Old Principle Revisited.

PMID- 27687205
TI  - Enhanced Preventative Therapy With Coronary Computed Tomographic Angiography:
      Added Value Beyond Simple Risk Calculators?

PMID- 27687207
TI  - Correction.

PMID- 27687206
TI  - Reply: Enhanced Preventative Therapy With Coronary Computed Tomographic
      Angiography: Added Value Beyond Simple Risk Calculators? AND Primum Non Nocere:
      Old Principle Revisited.

PMID- 27687208
TI  - Correction.

PMID- 27687209
TI  - Correction.

PMID- 27687210
TI  - Lack of mitochondrial DNA impairs chemical hypoxia-induced autophagy in liver
      tumor cells through ROS-AMPK-ULK1 signaling dysregulation independently of HIF
      1alpha.
AB  - Alterations in mitochondrial DNA (mtDNA) and autophagy activation are common
      events in tumors. Here we have investigated the effect of mitochondrial genome
      depletion on chemical hypoxia-induced autophagy in liver tumor cells. Human SK
      Hep-1 wild-type and mtDNA-depleted (Rho) cells were exposed to the hypoxia
      mimetic agents CoCl2 and deferoxamine (DFO). Up-regulation of HIF-1alpha, but not
      HIF-2alpha was observed. The expression of several HIF-1alpha target genes was
      also found. In human SK-Hep-1 and mouse Hepa 1-6 liver tumor cells, but not in
      the counterpart Rho derived lines, chemical hypoxia increased the abundance of
      autophagosomes and autolysosomes. In wild-type and Rho cells, chemical hypoxia
      induced down-regulation of HIF-1alpha-dependent autophagy inhibitors Bcl-2 and
      mTOR, whereas activation of AMPK/ULK1-mediated pro-autophagy pathway occurred
      only in wild-type cells. Chemical (compound C) and genetic (shRNA) inhibition of
      AMPK activation resulted in reduced autophagy. ATP levels were similar in both
      cell types, whereas constitutive and chemical hypoxia-induced reactive oxygen
      species (ROS) generation was lower in Rho cells. In wild-type cells, the
      antioxidant N-acetylcysteine blocked CoCl2- and DFO-induced AMPK and autophagy
      activation, but not endoplasmic reticulum stress induced by CoCl2. Enhanced Bax
      alpha/Bcl-2 ratio and cell death was induced by hypoxia mimetic agents more
      markedly in wild-type than in Rho cells. Upon blocking autophagy activation with
      3-methyladenine, DFO-induced cell death was partially prevented whereas that
      induced by CoCl2 was increased, but only in wild-type cells. These results
      suggest that mitochondrial dysfunction associated with the lack of mtDNA impairs
      the signaling pathways mediated by ROS, controlling autophagy activation in liver
      tumor cells, which may contributes to cancer development.

PMID- 27687212
TI  - Efficacy of Cognitive Behavioral Therapy for Generalized Anxiety Disorder in
      Older Adults: Systematic Review, Meta-Analysis, and Meta-Regression.
AB  - OBJECTIVE: Generalized anxiety disorder (GAD) is a common disorder in older
      adults producing functional impairment, and psychotherapy is the preferred
      treatment option. Meta-analytic methods sought to determine the efficacy of
      outpatient cognitive behavioral therapy (CBT) with respect to the hallmark
      feature of GAD-uncontrolled and excessive worry. In order to optimize clinical
      applicability, variables associated with GAD treatment outcomes were also
      examined. METHODS: Systematic search of relevant databases and iterative searches
      of references from articles retrieved. All studies were required to have been a
      randomized control trial (RCT), to have used the Penn State Worry Questionnaire
      (PSWQ) or its abbreviated version (PSWQ-A) as an outcome measure, and to have
      conducted CBT with outpatient older adults. Fourteen RCTs (N = 985) were suitable
      and random-effects meta-analyses and univariate meta-regressions were conducted.
      RESULTS: At the end of treatment, and at 6-month follow-up, significant treatment
      effects favoring CBT were found in comparison to a waitlist or treatment-as
      usual. When CBT was compared with active controls, a small nonsignificant
      treatment advantage was found for CBT at the end of treatment, with equivalence
      of outcomes at follow-up. Treatment effect size of CBT for GAD was significantly
      associated with attrition rates and depression outcomes. CONCLUSIONS: CBT is more
      helpful than having no treatment for GAD in later life. Nevertheless, whether CBT
      shows long-term durability, or is superior to other commonly available treatments
      (such as supportive psychotherapy), remains to be tested. The relationship
      between treatment effects for GAD and depression following CBT warrants further
      research.

PMID- 27687211
TI  - Tissue metabolism and host-microbial interactions in the intestinal mucosa.
AB  - In recent years, studies in the gastrointestinal (GI) mucosa have taught us a
      number of important lessons related to tissue oxygenation and metabolism in
      health and disease. The highly vascularized mucosa lies immediately adjacent to
      an anaerobic lumen containing trillions of metabolically active microbes (i.e.
      the microbiome) that results in one of the more austere tissue microenvironments
      in the body. These studies have also implicated a prominent role for oxygen
      metabolism and hypoxia in inflammation, so called "inflammatory hypoxia", that
      results from the activation of multiple oxygen consuming enzymes. Inflammation
      associated shifts in the composition of the microbiome and microbial-derived
      metabolites have revealed a prominent role for the transcription factor hypoxia
      inducible factor (HIF) in the regulation of key target genes that promote
      inflammatory resolution. Analyses of these pathways have provided a multitude of
      opportunities for understanding basic mechanisms of both homeostasis and disease
      and have defined new targets for intervention. Here, we review recent advances in
      our understanding of metabolic influences on host-microbe interactions in the GI
      mucosa.

PMID- 27687213
TI  - Facilitators and barriers to the use of standing orders for vaccination in
      obstetrics and gynecology settings.
AB  - BACKGROUND: Many young and middle-aged women receive their primary health care
      from their obstetrician-gynecologists. A recent change to vaccination
      recommendations during pregnancy has forced the integration of new clinical
      processes at obstetrician-gynecology practices. Evidence-based best practices for
      vaccination delivery include the establishment of vaccination standing orders.
      OBJECTIVES: As part of an intervention to increase adoption of evidence-based
      vaccination strategies for women in safety-net and private obstetrician
      gynecology settings, we conducted a qualitative study to identify the
      facilitators and barriers experienced by obstetrician-gynecology sites when
      establishing vaccination standing orders. STUDY DESIGN: At 6 safety-net and
      private obstetrician-gynecology practices, 51 semistructured interviews were
      completed by trained qualitative researchers over 2 years with clinical staff and
      vaccination program personnel. Standardized qualitative research methods were
      used during data collection and team-based data analysis to identify major themes
      and subthemes within the interview data. RESULTS: All study practices achieved
      partial to full implementation of vaccine standing orders for human
      papillomavirus, tetanus diphtheria pertussis, and influenza vaccines.
      Facilitating factors for vaccine standing order adoption included process
      standardization, acceptance of a continual modification process, and staff
      training. Barriers to vaccine standing order adoption included practice- and
      staff-level competing demands, pregnant women's preference for medical providers
      to discuss vaccine information with them, and staff hesitation in determining HPV
      vaccine eligibility. CONCLUSIONS: With guidance and commitment to integration of
      new processes, obstetrician-gynecology practices are able to establish vaccine
      standing orders for pregnant and nonpregnant women. Attention to certain process
      barriers can aid the adoption of processes to support the delivery of
      vaccinations in obstetrician-gynecology practice setting, and provide access to
      preventive health care for many women.

PMID- 27687214
TI  - Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during
      than after pregnancy.
AB  - BACKGROUND: Buprenorphine is a Food and Drug Administration-approved maintenance
      therapy for opioid use disorders and is increasingly being used in pregnant women
      with opioid use disorders as an alternative to methadone. Dosing of buprenorphine
      in pregnant women is based on the regimen recommended for nonpregnant females and
      males. Limited data are available defining the pharmacokinetic properties of
      sublingual buprenorphine administered during pregnancy. OBJECTIVE: This study
      evaluated the impact of physiological changes associated with pregnancy on the
      pharmacokinetics of sublingual buprenorphine during and after pregnancy. STUDY
      DESIGN: Pregnant women (n = 13), between 180/7 and 376/7 weeks' singleton
      gestation, receiving sublingual buprenorphine twice daily for opioid use
      disorders were studied. Pharmacokinetic-2 studies were performed between 18 and
      25 weeks (n = 7), pharmacokinetic-3 studies were performed between 31 and 37
      weeks (n = 11), and pharmacokinetic-P was performed 4-18 weeks postpartum (n =
      10). On the day of the study, blood was withdrawn prior to the daily morning dose
      of buprenorphine and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours after the
      dose. Buprenorphine plasma concentrations were analyzed by liquid chromatography
      tandem mass spectrometric detection. All pharmacokinetic parameters were observed
      or estimated using Microsoft Excel. Statistical analyses were performed to
      identify significant changes in study participants' buprenorphine pharmacokinetic
      parameter estimates over the duration of the study. Univariate linear and
      generalized linear mixed models were used to investigate changes in these
      measures over time, some of which were log transformed for normality. RESULTS:
      Dose-normalized (plasma concentration per dose) buprenorphine plasma
      concentrations were significantly lower during pregnancy (pharmacokinetic-2 plus
      pharmacokinetic-3) than during the postpartum period (pharmacokinetic-P).
      Specific pharmacokinetic parameters (and level of significance) were as follows:
      the area under the buprenorphine plasma concentration-time curves (P < .003),
      maximum buprenorphine concentrations (P < .018), buprenorphine concentrations at
      0 hour (P < .002), and buprenorphine concentrations at 12 hours (P < .001). None
      of these parameters differed significantly during pregnancy (ie, pharmacokinetic
      2 vs pharmacokinetic-3). The time to maximum buprenorphine concentrations did not
      differ significantly between groups. CONCLUSION: The dose-normalized plasma
      concentrations during a dosing interval and the overall exposure of buprenorphine
      (area under the buprenorphine plasma concentration-time curves) are lower
      throughout pregnancy compared with the postpartum period. This indicates an
      increase in apparent clearance of buprenorphine during pregnancy. These data
      suggest that pregnant women may need a higher dose of sublingual buprenorphine
      compared with postpartum individuals. The dose of buprenorphine should be
      assessed after delivery to maintain similar buprenorphine exposure during the
      postpartum period.

PMID- 27687215
TI  - Comments on prenatal diethylstilbestrol exposure and high-grade squamous cell
      neoplasia of the lower genital tract.

PMID- 27687217
TI  - Reply.

PMID- 27687216
TI  - Explaining the recent decrease in US infant mortality rate, 2007-2013.
AB  - BACKGROUND: The US infant mortality rate has been steadily decreasing in recent
      years as has the preterm birth rate; preterm birth is a major factor associated
      with death during the first year of life. The degree to which changes in
      gestational age-specific mortality and changes in the distribution of births by
      gestational age have contributed to the decrease in the infant mortality rate
      requires clarification. OBJECTIVE: The objective of the study was to better
      understand the major contributors to the 2007-2013 infant mortality decline for
      the total population and for infants born to non-Hispanic black, non-Hispanic
      white, and Hispanic women. STUDY DESIGN: We identified births and infant deaths
      from 2007 and 2013 Centers for Disease Control and Prevention National Vital
      Statistics System's period linked birth and infant death files. We included all
      deaths and births for which there was a reported gestational age at birth on the
      birth certificate of 22 weeks or greater. The decrease in the infant mortality
      rate was disaggregated such that all of the change could be attributed to
      improvements in gestational age-specific infant mortality rates and changes in
      the distribution of gestational age, by week of gestation, using the Kitagawa
      method. Sensitivity analyses were performed to account for records in which the
      obstetric estimate of gestational age was missing and for deaths and births less
      than 22 weeks' gestation. Maternal race and ethnicity information was obtained
      from the birth certificate. RESULTS: The infant mortality rates after exclusions
      were 5.72 and 4.92 per 1000 live births for 2007 and 2013, respectively, with an
      absolute difference of -0.80 (14% decrease). Infant mortality rates declined by
      11% for non-Hispanic whites, by 19% for non-Hispanic blacks, and by 14% for
      Hispanics during the period. Compared with 2007, the proportion of births in each
      gestational age category was lower in 2013 with the exception of 39 weeks during
      which there was an increase in the proportion of births from 30.1% in 2007 to
      37.5% in 2013. Gestational age-specific mortality decreased for each gestational
      age category between 2007 and 2013 except 33 weeks and >42 weeks. About 31% of
      the decrease in the US infant mortality rate from 2007 through 2013 was due to
      changes in the gestational age distribution, and 69% was due to improvements in
      gestational age-specific survival. Improvements in the gestational age
      distribution from 2007 through 2013 benefited infants of non-Hispanic white women
      (48%) the most, followed by infants of non-Hispanic black (31%) and Hispanic
      (14%) women. CONCLUSION: Infant mortality improved between 2007 and 2013 as a
      result of both improvements in the distribution of gestational age at birth and
      improvements in survival after birth. The differential contribution of
      improvements in the gestational age distribution at birth by race and ethnicity
      suggests that preconception and antenatal health and health care aimed at
      preventing or delaying preterm birth may not be reaching all populations.

PMID- 27687221
TI  - Kinetic of orange pigment production from Monascus ruber on submerged
      fermentation.
AB  - Pigments produced by species of Monascus have been used to coloring rice, meat,
      sauces, wines and beers in East Asian countries. Monascus can produce orange
      (precursor), yellow and red pigments. Orange pigments have low solubility in
      culture media and when react with amino groups they become red and largely
      soluble. The orange pigments are an alternative to industrial pigment production
      because the low solubility facilitates the downstream operations. The aim of this
      work was to study the kinetic on the production of orange pigments by Monascus
      ruber CCT 3802. The shaking frequency of 300 rpm was favorable to production,
      whereas higher shaking frequencies showed negative effect. Pigment production was
      partially associated with cell growth, the critical dissolved oxygen
      concentration was between 0.894 and 1.388 mgO2 L-1 at 30  degrees C, and limiting
      conditions of dissolved oxygen decreased the production of orange pigments. The
      maintenance coefficient (mo) and the conversion factor of oxygen in biomass (Yo)
      were 18.603 mgO2 g x-1  h-1 and 3.133 gx gO 2-1 and the consideration of these
      parameters in the oxygen balance to estimate the biomass concentration provided
      good fits to the experimental data.

PMID- 27687218
TI  - Changes in brain oxysterols at different stages of Alzheimer's disease: Their
      involvement in neuroinflammation.
AB  - Alzheimer's disease (AD) is a gradually debilitating disease that leads to
      dementia. The molecular mechanisms underlying AD are still not clear, and at
      present no reliable biomarkers are available for the early diagnosis. In the last
      several years, together with oxidative stress and neuroinflammation, altered
      cholesterol metabolism in the brain has become increasingly implicated in AD
      progression. A significant body of evidence indicates that oxidized cholesterol,
      in the form of oxysterols, is one of the main triggers of AD. The oxysterols
      potentially most closely involved in the pathogenesis of AD are 24
      hydroxycholesterol and 27-hydroxycholesterol, respectively deriving from
      cholesterol oxidation by the enzymes CYP46A1 and CYP27A1. However, the possible
      involvement of oxysterols resulting from cholesterol autooxidation, including 7
      ketocholesterol and 7beta-hydroxycholesterol, is now emerging. In a systematic
      analysis of oxysterols in post-mortem human AD brains, classified by the Braak
      staging system of neurofibrillary pathology, alongside the two oxysterols of
      enzymatic origin, a variety of oxysterols deriving from cholesterol autoxidation
      were identified; these included 7-ketocholesterol, 7alpha-hydroxycholesterol,
      4beta-hydroxycholesterol, 5alpha,6alpha-epoxycholesterol, and 5beta,6beta
      epoxycholesterol. Their levels were quantified and compared across the disease
      stages. Some inflammatory mediators, and the proteolytic enzyme matrix
      metalloprotease-9, were also found to be enhanced in the brains, depending on
      disease progression. This highlights the pathogenic association between the
      trends of inflammatory molecules and oxysterol levels during the evolution of AD.
      Conversely, sirtuin 1, an enzyme that regulates several pathways involved in the
      anti-inflammatory response, was reduced markedly with the progression of AD,
      supporting the hypothesis that the loss of sirtuin 1 might play a key role in AD.
      Taken together, these results strongly support the association between changes in
      oxysterol levels and AD progression.

PMID- 27687222
TI  - Dysfunctional Pain Modulation in Torture Survivors: The Mediating Effect of PTSD.
AB  - : Trauma survivors, and particularly torture survivors, suffer from high rates of
      chronic pain and posttraumatic stress disorder (PTSD) for years afterward, along
      with alterations in the function of the pain system. On the basis of longitudinal
      data on PTSD symptomatology, we tested whether exposure to torture, PTSD or PTSD
      trajectories accounted for chronic pain and altered pain perception. Participants
      were 59 torture survivors and 44 age-matched healthy control subjects. Chronic
      pain was characterized. Pain threshold, pain tolerance, conditioned pain
      modulation (CPM), and temporal summation of pain were measured. Three PTSD
      trajectories were identified among torture survivors; chronic, delayed, and
      resilient. Lack of CPM and more intense chronic pain was found among the chronic
      and delayed groups compared with the resilient and healthy control groups.
      Temporal summation of pain was strongest among the chronic group. PTSD
      trajectories mediated the relationship between torture and CPM. It appears that
      the duration and severity of posttraumatic distress, rather than the exposure to
      trauma, are crucial factors that mediate the association between trauma and
      chronic pain. Because PTSD and its resultant distress are measurable, their
      evaluation seems particularly important in the management of pain among trauma
      survivors. The results may be generalized to other instances in which chronic
      pain persists after traumatic events. PERSPECTIVE: This article presents the
      mediation effect of PTSD trajectory on pain modulation among trauma survivors
      suggesting that it is the duration and severity of PTSD/distress, rather than the
      exposure to trauma per se, that influence the perception and modulation of pain.

PMID- 27687220
TI  - Glutathione maintenance mitigates age-related susceptibility to redox cycling
      agents.
AB  - Isolated hepatocytes from young (4-6mo) and old (24-26mo) F344 rats were exposed
      to increasing concentrations of menadione, a vitamin K derivative and redox
      cycling agent, to determine whether the age-related decline in Nrf2-mediated
      detoxification defenses resulted in heightened susceptibility to xenobiotic
      insult. An LC50 for each age group was established, which showed that aging
      resulted in a nearly 2-fold increase in susceptibility to menadione (LC50 for
      young: 405MUM; LC50 for old: 275MUM). Examination of the known Nrf2-regulated
      pathways associated with menadione detoxification revealed, surprisingly, that
      NAD(P)H: quinone oxido-reductase 1 (NQO1) protein levels and activity were
      induced 9-fold and 4-fold with age, respectively (p=0.0019 and p=0.018; N=3), but
      glutathione peroxidase 4 (GPX4) declined by 70% (p=0.0043; N=3). These results
      indicate toxicity may stem from vulnerability to lipid peroxidation instead of
      inadequate reduction of menadione semi-quinone. Lipid peroxidation was 2-fold
      higher, and GSH declined by a 3-fold greater margin in old versus young rat cells
      given 300uM menadione (p<0.05 and p<=0.01 respectively; N=3). We therefore
      provided 400uMN-acetyl-cysteine (NAC) to hepatocytes from old rats before
      menadione exposure to alleviate limits in cysteine substrate availability for GSH
      synthesis during challenge. NAC pretreatment resulted in a >2-fold reduction in
      cell death, suggesting that the age-related increase in menadione susceptibility
      likely stems from attenuated GSH-dependent defenses. This data identifies
      cellular targets for intervention in order to limit age-related toxicological
      insults to menadione and potentially other redox cycling compounds.

PMID- 27687219
TI  - Resistance training and redox homeostasis: Correlation with age-associated
      genomic changes.
AB  - Regular physical activity is effective as prevention and treatment for different
      chronic conditions related to the ageing processes. In fact, a sedentary
      lifestyle has been linked to a worsening of cellular ageing biomarkers such as
      telomere length (TL) and/or specific epigenetic changes (e.g. DNA methylation),
      with increase of the propensity to aging-related diseases and premature death.
      Extending our previous findings, we aimed to test the hypothesis that 12 weeks of
      low frequency, moderate intensity, explosive-type resistance training (EMRT) may
      attenuate age-associated genomic changes. To this aim, TL, global DNA
      methylation, TRF2, Ku80, SIRT1, SIRT2 and global protein acetylation, as well as
      other proteins involved in apoptotic pathway (Bcl-2, Bax and Caspase-3),
      antioxidant response (TrxR1 and MnSOD) and oxidative damage (myeloperoxidase)
      were evaluated before and after EMRT in whole blood or peripheral mononuclear
      cells (PBMCs) of elderly subjects. Our findings confirm the potential of EMRT to
      induce an adaptive change in the antioxidant protein systems at systemic level
      and suggest a putative role of resistance training in the reduction of global DNA
      methylation. Moreover, we observed that EMRT counteracts the telomeres'
      shortening in a manner that proved to be directly correlated with the
      amelioration of redox homeostasis and efficacy of training regime, evaluated as
      improvement of both muscle's power/strength and functional parameters.

PMID- 27687223
TI  - Dorsal Root Ganglionic Field Stimulation Relieves Spontaneous and Induced
      Neuropathic Pain in Rats.
AB  - : Dorsal root ganglion (DRG) electrical stimulation (ganglionic field stimulation
      [GFS]) is effective in relieving clinical pain, but its mechanism is unknown. We
      therefore developed a rat model for GFS to test analgesic effects in the context
      of neuropathic pain. GFS was applied with a bipolar electrode at L4, using
      parameters replicating clinical use (20 Hz, 150-MUs pulse width, current at 80%
      of motor threshold). Neuropathic pain was generated by tibial nerve injury (TNI).
      Pain behavior was monitored by determining the threshold for withdrawal from
      punctate mechanical stimuli, by identifying hyperalgesic responses to noxious
      mechanical stimuli, and by hypersensitivity to cold. The affective dimension of
      pain was measured using conditioned place preference. We found that electrode
      insertion caused no behavioral evidence of pain and produced no histological
      evidence of DRG damage. GFS reversed TNI-induced hypersensitivity to cold and
      mechanical hyperalgesia and allodynia. Allodynia remained diminished 15 minutes
      after GFS. Conditioned place preference showed that GFS was not rewarding in
      uninjured control animals but was rewarding in animals subjected to TNI, which
      reveals analgesic efficacy of GFS for spontaneous pain. We conclude that GFS
      relieves neuropathic pain in rats. This model may provide a platform for
      identifying mechanisms and novel applications of GFS. PERSPECTIVE: We show that
      electrical stimulation of the DRG in rats reverses neuropathic pain behavior and
      provides a rewarding effect to animals with spontaneous neuropathic pain. This
      confirms analgesic efficacy of DRG stimulation in an animal model, and provides a
      platform for preclinical exploration.

PMID- 27687224
TI  - Real time observation and automated measurement of red blood cells agglutination
      inside a passive microfluidic biochip containing embedded reagents.
AB  - The process of agglutination is commonly used for the detection of biomarkers
      like proteins or viruses. The multiple bindings between micrometer sized
      particles, either latex beads or red blood cells (RBCs), create aggregates that
      are easily detectable and give qualitative information about the presence of the
      biomarkers. In most cases, the detection is made by simple naked-eye observation
      of agglutinates without any access to the kinetics of agglutination. In this
      study, we address the development of a real-time time observation of RBCs
      agglutination. Using ABO blood typing as a proof-of-concept, we developed i) an
      integrated biological protocol suitable for further use as point-of-care (POC)
      analysis and ii) two dedicated image processing algorithms for the real-time and
      quantitative measurement of agglutination. Anti-A or anti-B typing reagents were
      dried inside the microchannel of a passive microfluidic chip designed to enhance
      capillary flow. A blood drop deposit at the tip of the biochip established a
      simple biological protocol. In situ agglutination of autologous RBCs was achieved
      by means of embedded reagents and real time agglutination process was monitored
      by video recording. Using a training set of 24 experiments, two real-time
      indicators based on correlation and variance of gray levels were optimized and
      then further confirmed on a validation set. 100% correct discrimination between
      positive and negative agglutinations was performed within less than 2min by
      measuring real-time evolution of both correlation and variance indicators.

PMID- 27687225
TI  - Global transcriptional regulator TrmB family members in prokaryotes.
AB  - Members of the TrmB family act as global transcriptional regulators for the
      activation or repression of sugar ABC transporters and central sugar metabolic
      pathways, including glycolytic, gluconeogenic, and other metabolic pathways, and
      also as chromosomal stabilizers in archaea. As a relatively newly classified
      transcriptional regulator family, there is limited experimental evidence for
      their role in Thermococcales, halophilic archaeon Halobacterium salinarum NRC1,
      and crenarchaea Sulfolobus strains, despite being one of the extending protein
      families in archaea. Recently, the protein structures of Pyrococcus furiosus TrmB
      and TrmBL2 were solved, and the transcriptomic data uncovered by microarray and
      ChIP-Seq were published. In the present review, recent evidence of the functional
      roles of TrmB family members in archaea is explained and extended to bacteria. 

PMID- 27687226
TI  - Diversity and enzyme activity of Penicillium species associated with macroalgae
      in Jeju Island.
AB  - A total of 28 strains of 19 Penicillium species were isolated in a survey of
      extracellular enzyme-producing fungi from macroalgae along the coast of Jeju
      Island of Korea. Penicillium species were identified based on morphological and
      beta-tubulin sequence analyses. In addition, the halo-tolerance and enzyme
      activity of all strains were evaluated. The diversity of Penicillium strains
      isolated from brown algae was higher than the diversity of strains isolated from
      green and red algae. The commonly isolated species were Penicillium antarcticum,
      P. bialowiezense, P. brevicompactum, P. crustosum, P. oxalicum, P. rubens, P.
      sumatrense, and P. terrigenum. While many strains showed endoglucanase, beta
      glucosidase, and protease activity, no alginase activity was detected. There was
      a positive correlation between halo-tolerance and endoglucanase activity within
      Penicillium species. Among 19 Penicillium species, three species-P. kongii, P.
      olsonii, and P. viticola-have not been previously recorded in Korea. 

PMID- 27687227
TI  - Arcobacter acticola sp. nov., isolated from seawater on the East Sea in South
      Korea.
AB  - A Gram-stain-negative, facultative aerobic, non-flagellated, and rod-shaped
      bacterium, designated AR-13(T), was isolated from a seawater on the East Sea in
      South Korea, and subjected to a polyphasic taxonomic study. Strain AR-13(T) grew
      optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 0-0.5% (w/v)
      NaCl. The phylogenetic trees based on 16S rRNA gene sequences showed that strain
      AR-13(T) fell within the clade comprising the type strains of Arcobacter species,
      clustering coherently with the type strain of Arcobacter venerupis. Strain AR
      13(T) exhibited 16S rRNA gene sequence similarity values of 98.1% to the type
      strain of A. venerupis and of 93.2-96.9% to the type strains of the other
      Arcobacter species. Strain AR-13(T) contained MK-6 as the only menaquinone and
      summed feature 3 (C16:1 omega7c and/or C16:1 omega6c), C16:0, C18:1 omega7c, and
      summed feature 2 (iso-C16:1 I and/or C14:0 3-OH) as the major fatty acids. The
      major polar lipids detected in strain AR-13(T) were phosphatidylethanolamine,
      phosphatidylglycerol, and one unidentified aminophospholipid. The DNA G+C content
      was 28.3 mol% and its mean DNA-DNA relatedness value with the type strain of A.
      venerupis was 21%. Differential phenotypic properties, together with its
      phylogenetic and genetic distinctiveness, revealed that strain AR-13(T) is
      separated from recognized Arcobacter species. On the basis of the data presented,
      strain AR-13(T) is considered to represent a novel species of the genus
      Arcobacter, for which the name Arcobacter acticola sp. nov. is proposed. The type
      strain is AR-13(T) (=KCTC 52212(T) =NBRC 112272(T)). 

PMID- 27687228
TI  - RraAS2 requires both scaffold domains of RNase ES for high-affinity binding and
      inhibitory action on the ribonucleolytic activity.
AB  - RraA is a protein inhibitor of RNase E (Rne), which catalyzes the
      endoribonucleolytic cleavage of a large proportion of RNAs in Escherichia coli.
      The antibiotic-producing bacterium Streptomyces coelicolor also contains homologs
      of RNase E and RraA, designated as RNase ES (Rns), RraAS1, and RraAS2,
      respectively. Here, we report that RraAS2 requires both scaffold domains of RNase
      ES for high-affinity binding and inhibitory action on the ribonucleolytic
      activity. Analyses of the steady-state level of RNase E substrates indicated that
      coexpression of RraAS2 in E. coli cells overproducing Rns effectively inhibits
      the ribonucleolytic activity of full-length RNase ES, but its inhibitory effects
      were moderate or undetectable on other truncated forms of Rns, in which the N-
      or/and C-terminal scaffold domain was deleted. In addition, RraAS2 more
      efficiently inhibited the in vitro ribonucleolytic activity of RNase ES than that
      of a truncated form containing the catalytic domain only. Coimmunoprecipitation
      and in vivo cross-linking experiments further showed necessity of both scaffold
      domains of RNase ES for high-affinity binding of RraAS2 to the enzyme, resulting
      in decreased RNA-binding capacity of RNase ES. Our results indicate that RraAS2
      is a protein inhibitor of RNase ES and provide clues to how this inhibitor
      affects the ribonucleolytic activity of RNase ES. 

PMID- 27687229
TI  - Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc
      transferases expressed in Saccharomyces cerevisiae.
AB  - O-linked beta-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post
      translational modification in many cellular processes. It is mediated by O-GlcNAc
      transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or
      threonine residues of the target proteins. In this study, we expressed a putative
      Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum
      Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as
      recombinant proteins in Saccharomyces cerevisiae, and performed their functional
      characterization. Immunoblotting assays using antibody against O-GlcNAc revealed
      that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes
      auto-O-GlcNAcylation in the heterologous host S. cerevisiae. Moreover, the rhOGT
      expressed in S. cerevisiae showed a catalytic activity during in vitro assays
      using casein kinase II substrates, whereas no such activity was obtained in
      rYlOGT. However, the chimeric human-Y. lipolytica OGT, carrying the human
      tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic
      domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro
      assays. Although the overexpression of full-length OGTs inhibited the growth of
      S. cerevisiae, no such inhibition was obtained upon overexpression of only the
      CTD fragment, indicating the role of TPR domain in growth inhibition. This is the
      first report on the functional analysis of the fungal OGT, indicating that the Y.
      lipolytica OGT retains its catalytic activity, although the physiological role
      and substrates of YlOGT remain to be elucidated. 

PMID- 27687230
TI  - Degradation and polymerization of monolignols by Abortiporus biennis, and
      induction of its degradation with a reducing agent.
AB  - This study was carried out to better understand the characteristic modification
      mechanisms of monolignols by enzyme system of Abortiporus biennis and to induce
      the degradation of monolignols. Degradation and polymerization of monolignols
      were simultaneously induced by A. biennis. Whole cells of A. biennis degraded
      coniferyl alcohol to vanillin and coniferyl aldehyde, and degraded sinapyl
      alcohol to 2,6-dimethoxybenzene- 1,4-diol, with the production of dimers. The
      molecular weight of monolignols treated with A. biennis increased drastically.
      The activities of lignin degrading enzymes were monitored for 24 h to determine
      whether there was any correlation between monolignol biomodification and
      ligninolytic enzymes. We concluded that complex enzyme systems were involved in
      the degradation and polymerization of monolignols. To degrade monolignols,
      ascorbic acid was added to the culture medium as a reducing agent. In the
      presence of ascorbic acid, the molecular weight was less increased in the case of
      coniferyl alcohol, while that of sinapyl alcohol was similar to that of the
      control. Furthermore, the addition of ascorbic acid led to the production of
      various degraded compounds: syringaldehyde and acid compounds. Accordingly, these
      results demonstrated that ascorbic acid prevented the rapid polymerization of
      monolignols, thus stabilizing radicals generated by enzymes of A. biennis.
      Thereafter, A. biennis catalyzed the oxidation of stable monolignols. As a
      result, ascorbic acid facilitated predominantly monolignols degradation by A.
      biennis through the stabilization of radicals. These findings showed outstanding
      ability of A. biennis to modify the lignin compounds rapidly and usefully. 

PMID- 27687231
TI  - Molecular epidemiology of norovirus in asymptomatic food handlers in Busan,
      Korea, and emergence of genotype GII.17.
AB  - The molecular epidemiology of norovirus infections was studied in food handlers
      without any symptoms from January to December 2015 in Busan city, Korea. A total
      of 2,174 fecal specimens from asymptomatic food handlers were analyzed, and 2.3%
      (49/2,174) were norovirus-positive. Fourteen of 335 samples (4.2%) were positive
      in January; fifteen of 299 samples (5.0%) in February, and seven of 189 samples
      (3.7%) in December. However, norovirus was rarely detected in other months. From
      sequencing analysis, 11 genotypes (five GI and six GII genotypes) were detected.
      Among the 42 capid gene sequences identified, 14 were from the GI genogroup,
      while 28 were from the GII genogroup. The most commonly detected genotype was
      GII.17, comprising 15 (35.7%) of positive samples. From January 2012 to December
      2015, 5,138 samples were collected from gastroenteritis patients and outbreaks in
      Busan. The most detected genotype in 2012, 2013, and 2014 was GII.4 (121, 24, and
      12 cases, respectively), but in 2015, GII.17 (25 cases) was the most common. The
      GII.4 genotype was the major cause of acute gastroenteritis from 2012 to 2014,
      but the GII.17 genotype became the most prevalent cause in 2015. Continued
      epidemiological surveillance of GII.17 is needed, together with assessment of the
      risk of norovirus infection. 

PMID- 27687233
TI  - Erratum to: Transcriptional control of sexual development in Cryptococcus
      neoformans.

PMID- 27687232
TI  - MDA7/IL-24 is an anti-viral factor that inhibits influenza virus replication.
AB  - Melanoma differentiation associated gene-7 (mda-7)/interleukin- 24 (IL-24) is a
      secreted cytokine, which plays an essential role in tumor suppression. Although
      its role as a multifunctional protein affecting broad types of cancers is well
      described, functions of IL-24 in host defense against virus infection are yet to
      be determined. In this study, we explored the anti-viral effect of recombinant IL
      24 treatment during influenza infection. Infection of human lung adenocarcinoma
      cells (A549) with the influenza A virus up-regulated IL-24 mRNA and protein
      expression in a time-dependent manner. Pre-treatment of A549 cells with
      recombinant IL-24 protein effectively suppressed viral plaque formation.
      Furthermore, IL-24 treatment of A549 cells reduced viral non-structural protein 1
      (NS1) synthesis, whereas IL-24 knockdown resulted in increased viral replication.
      Interestingly, IL-24 treatment following influenza A virus infection led to up
      regulation of interferon (IFN)-induced antiviral signaling. Taken together, our
      results suggest that IL-24 exerts a potent suppressive effect on influenza viral
      replication and can be used in the treatment of influenza infection. 

PMID- 27687234
TI  - Finding the Right Treatment for Achalasia Treatment: Risks, Efficacy,
      Complications.
AB  - OPINION STATEMENT: Achalasia is a primary esophageal motor disorder of the
      esophagus that is characterized by the absence of esophageal peristalsis and a
      failure of the lower esophageal sphincter (LES) to relax upon swallowing. The
      defective relaxation leads to symptoms of dysphagia for solids and liquids,
      regurgitation, aspiration, chest pain, and weight loss. Achalasia is believed to
      result from a selective loss of enteric inhibitory neurons, most likely due to an
      autoimmune phenomenon in genetic susceptible individuals. As there is no curative
      treatment for achalasia, treatment is confined to disruption of the LES to
      improve bolus passage. The two most commonly used treatment modalities available
      are the endoscopic pneumodilation (PD) and the surgical laparoscopic Heller
      myotomy (LHM). A recent European randomized controlled trial showed that both
      treatment modalities have comparable success rates after a follow-up of at least
      5 years. In view of these data, both treatments can be used as an initial therapy
      in achalasia and the choice should be based on the expertise available. Recently,
      a new endoscopic technique, peroral endoscopic myotomy (POEM), has been
      introduced with excellent short-term success rates. However, longer follow-up and
      data from randomized controlled trials are needed before accepting this technique
      as a new treatment option for achalasia in clinical practice.

PMID- 27687235
TI  - Design and application of a tool for structuring, capitalizing and making more
      accessible information and lessons learned from accidents involving machinery.
AB  - Accident reports are published in order to communicate the information and
      lessons learned from accidents. An efficient accident recording and analysis
      system is a necessary step towards improvement of safety. However, currently
      there is a shortage of efficient tools to support such recording and analysis. In
      this study we introduce a flexible and customizable tool that allows structuring
      and analysis of this information. This tool has been implemented under TEEXMA(r).
      We named our prototype TEEXMA(r)SAFETY. This tool provides an information
      management system to facilitate data collection, organization, query, analysis
      and reporting of accidents. A predefined information retrieval module provides
      ready access to data which allows the user to quickly identify the possible
      hazards for specific machines and provides information on the source of hazards.
      The main target audience for this tool includes safety personnel, accident
      reporters and designers. The proposed data model has been developed by analyzing
      different accident reports.

PMID- 27687236
TI  - Distribution of microRNA biomarker candidates in solid tissues and body fluids.
AB  - Small non-coding RNAs, especially microRNAs, are discussed as promising
      biomarkers for a substantial number of human pathologies. A broad understanding
      in which solid tissues, cell types or body fluids a microRNA is expressed helps
      also to understand and to improve the suitability of miRNAs as non- or minimally
      invasive disease markers. We recently reported the Human miRNA Tissue Atlas (
      http://www.ccb.uni-saarland.de/tissueatlas ) containing 105 miRNA profiles of 31
      organs from 2 corpses. We subsequently added miRNA profiles measured by others
      and us using the same array technology as for the first version of the Human
      miRNA Tissue Atlas. The latter profiles stem from 163 solid organs including
      lung, prostate and gastric tissue, from 253 whole blood samples and 66 fractioned
      blood cell isolates, from body fluids including 72 serum samples, 278 plasma
      samples, 29 urine samples, and 16 saliva samples and from different collection
      and storage conditions. While most miRNAs are ubiquitous abundant in solid
      tissues and whole blood, we also identified miRNAs that are rather specific for
      tissues. Our web-based repository now hosting 982 full miRNomes all of which are
      measured by the same microarray technology. The knowledge of these variant
      abundances of miRNAs in solid tissues, in whole blood and in other body fluids is
      essential to judge the value of miRNAs as biomarker.

PMID- 27687237
TI  - Successful treatment of relapsed/refractory Hodgkins lymphoma with nivolumab in a
      heavily pretreated patient with progressive disease after both autologous and
      allogeneic stem cell transplantation.

PMID- 27687239
TI  - Specialization of CDK regulation under DNA damage.

PMID- 27687240
TI  - When love hurts. A systematic review on the effects of surgical and
      pharmacological treatments for endometriosis on female sexual functioning.
AB  - INTRODUCTION: Endometriosis is associated with an increased risk of dyspareunia,
      therefore this chronic gynecologic disease should be considered as a major cause
      of sexual dysfunctions. The aims of this study were to review the literature on
      the effects of surgical and pharmacological treatments for endometriosis on
      female sexual functioning, and to provide suggestions for future treatment
      strategies. MATERIAL AND METHODS: We followed the PRISMA guidelines to conduct
      this systematic review, which involved an electronic database search of studies
      on the association between endometriosis and sexuality published between 2000 and
      2016. RESULTS: As a result of the screening process, 22 studies were included in
      this systematic review. The 22 studies included were divided into two categories:
      (a) surgical intervention studies (n = 17), examining postoperative sexual
      outcomes of surgery for endometriosis; (b) pharmacological intervention studies
      (n = 5), evaluating the effects of pharmacological endometriosis treatments on
      sexual functioning. The studies considered showed that overall surgical and
      pharmacological interventions for endometriosis can lead to medium-/long-term
      improvement, but not necessarily to a definitive resolution of female sexual
      dysfunctions due to endometriosis. CONCLUSIONS: Sexual functioning is a
      multidimensional phenomenon and the ideal treatment for endometriosis-related
      sexual dysfunctions should be conducted by a multidisciplinary team that involves
      not only gynecologists, but also sexologists and psychologists/psychotherapists.
      Improving global sexual functioning, and not just reducing pain at intercourse,
      should be considered as a major clinical goal of endometriosis treatment.

PMID- 27687242
TI  - Sociocultural factors contributing to teenage pregnancy in Zomba district,
      Malawi.
AB  - This study explores sociocultural and other risk factors associated with
      unplanned teenage pregnancy in Zomba district of Malawi. Data were obtained from
      505 participants under the age of 20 years using a questionnaire administered
      through face-to-face interviews held at five antenatal clinics. The data were
      analysed using descriptive statistics, frequency tables and chi-square analysis
      which allowed comparative understanding of the sociocultural risk factors for
      planned and unplanned teenage pregnancy in Zomba district. The findings revealed
      that teenage pregnancy is a major health and social problem. Over 76% of the
      teenage respondents in the study had experienced unplanned pregnancy. Among the
      prominent factors that stood out in the analysis for this high rate of teenage
      pregnancy were early sex and marriage, low contraceptive use, low educational
      levels, low socio-economic status, lack of knowledge of reproductive and sexual
      health, gender inequity, and physical/sexual violence. The consequences on
      teenage mothers of unplanned pregnancy have been tragic and have compromised
      their physical, psychological and socioeconomic wellbeing, not just on them but
      also their families and society at large. The findings point to the need for a
      multi-sectoral approach to tackle the problem on teenage pregnancy in this
      district, and likely throughout Malawi.

PMID- 27687241
TI  - The role of mitogen-activated protein kinases and sterol receptor coactivator-1
      in TGF-beta-regulated expression of genes implicated in macrophage cholesterol
      uptake.
AB  - The anti-atherogenic cytokine TGF-beta inhibits macrophage foam cell formation by
      suppressing the expression of key genes implicated in the uptake of modified
      lipoproteins. We have previously shown a critical role for p38 MAPK and JNK in
      the TGF-beta-mediated regulation of apolipoprotein E expression in human
      monocytes. However, the roles of these two MAPK pathways in the control of
      expression of key genes involved in the uptake of modified lipoproteins in human
      macrophages is poorly understood and formed the focus of this study. TGF-beta
      activated both p38 MAPK and JNK, and knockdown of p38 MAPK or c-Jun, a key
      downstream target of JNK action, demonstrated their requirement in the TGF-beta
      inhibited expression of several key genes implicated in macrophage lipoprotein
      uptake. The potential role of c-Jun and specific co-activators in the action of
      TGF-beta was investigated further by studies on the lipoprotein lipase gene. c
      Jun did not directly interact with the minimal promoter region containing the TGF
      beta response elements and a combination of transient transfection and knock down
      assays revealed an important role for SRC-1. These studies provide novel insights
      into the mechanisms underlying the TGF-beta-mediated inhibition of macrophage
      gene expression associated with the control of cholesterol homeostasis.

PMID- 27687243
TI  - Measuring maternal mortality using a Reproductive Age Mortality Study (RAMOS).
AB  - BACKGROUND: Assessing the feasibility of conducting a prospective Reproductive
      Age Mortality Survey (RAMOS) study in the low-income setting of Mangochi
      District, Malawi to obtain cotemporaneous estimates of the number, cause of and
      conditions associated with maternal deaths (MD) in all women of reproductive age
      (WRA) (n = 207 688). METHODS: MD among all deaths of WRA were identified using
      the ICD-10 definition. Cause of death and contributing conditions identified by a
      panel of experts using the classification system for deaths during pregnancy,
      childbirth and puerperium (ICD-MM). RESULTS: Out of 424 deaths of WRA, 151 were
      MD giving a Maternal Mortality Ratio (MMR) of 363 per 100,000 live births (95 %
      CI: 307-425). Only 86 MD had been reported via existing reporting mechanisms
      representing an underreporting of 43 %. The majority of MD (62.3 %) occurred in a
      health facility and were the result of direct obstetric causes (74.8 %) with
      obstetric haemorrhage as the leading cause (35.8 %), followed by pregnancy
      related infections (19.4 %), hypertensive disorders (16.8 %) and pregnancy with
      abortive outcome (13.2 %). Malaria was the most frequently identified indirect
      cause (9.9 %). Contributing conditions were more frequently identified when both
      verbal autopsy and facility-based death review had taken place and included
      obstructed labour (28.5 %), anaemia (12.6 %) and positive HIV status (4.0 %).
      CONCLUSION: The high number of MD that occur at health facility level, cause of
      death and contributing conditions reflect deficiencies in the quality of care at
      health facility level. A RAMOS is feasible in low- and middle-income settings and
      provides contemporaneous estimates of MMR.

PMID- 27687244
TI  - Adaptive pattern of nectar volume within inflorescences: bumblebee foraging
      behavior and pollinator-mediated natural selection.
AB  - Larger floral displays increase pollinator visitation as well as among-flower
      self-pollination (geitonogamy) in self-compatible species. Dichogamy (temporal
      separation of gender expression) can limit geitonogamy and increase outcrossing
      but this depends on pollinator behavior within inflorescences. Declining nectar
      volume from lower to upper flowers is a hypothesized adaptation to increase
      outcrossing and pollen export by encouraging the upward movment of pollinators
      from female to male flowers and by reducing the number of flowers probed per
      inflorescence, but supporting evidence has been equivocal. We tested this
      hypothesis in Aconitum gymnandrum by studying floral display and rewards,
      pollinator visitation, and pollinator-mediated selection on floral traits. We
      found that larger inflorescences of A. gymnandrum attracted more pollinators, but
      did not increase the number of flowers probed per visit. Nectar production
      declined with increasing flower height on average, but the opposite pattern was
      also common. Bumblebees responded strongly to the nectar pattern, moving from
      higher to lower nectar concentration. Finally, there was significant pollinator
      mediated direct selection for this pattern of declining nectar volume after
      correcting for correlations with flower size, number, and mean nectar volume.
      Together, the results strongly suggest that declining nectar production in higher
      flowers is an adaptation to enhance outcrossing in A. gymnandrum.

PMID- 27687245
TI  - Chemotaxis towards autoinducer 2 mediates autoaggregation in Escherichia coli.
AB  - Bacteria communicate by producing and sensing extracellular signal molecules
      called autoinducers. Such intercellular signalling, known as quorum sensing,
      allows bacteria to coordinate and synchronize behavioural responses at high cell
      densities. Autoinducer 2 (AI-2) is the only known quorum-sensing molecule
      produced by Escherichia coli but its physiological role remains elusive, although
      it is known to regulate biofilm formation and virulence in other bacterial
      species. Here we show that chemotaxis towards self-produced AI-2 can mediate
      collective behaviour-autoaggregation-of E. coli. Autoaggregation requires
      motility and is strongly enhanced by chemotaxis to AI-2 at physiological cell
      densities. These effects are observed regardless whether cell-cell interactions
      under particular growth conditions are mediated by the major E. coli adhesin
      (antigen 43) or by curli fibres. Furthermore, AI-2-dependent autoaggregation
      enhances bacterial stress resistance and promotes biofilm formation.

PMID- 27687246
TI  - Europium (III) Organic Complexes in Porous Boron Nitride Microfibers: Efficient
      Hybrid Luminescent Material.
AB  - We report the design and synthesis of a novel kind of organic-inorganic hybrid
      material via the incorporation of europium (III) beta-diketonate complexes
      (Eu(TTA)3, TTA = 2-thenoyltrifluoroacetone) into one-dimensional (1D) porous
      boron nitride (BN) microfibers. The developed Eu(TTA)3@BN hybrid composites with
      typical 1D fibrous morphology exhibit bright visible red-light emission on UV
      illumination. The confinement of Eu(TTA)3 within pores of BN microfibers not only
      decreases the aggregation-caused quenching in solid Eu(TTA)3, but also improves
      their thermal stabilities. Moreover, The strong interactions between Eu(TTA)3 and
      porous BN matrix result in an interesting energy transfer process from BN host to
      TTA ligand and TTA ligand to Eu3+ ions, leading to the remarkable increase of red
      emission. The synthetic approach should be a very promising strategy which can be
      easily expanded to other hybrid luminescent materials based on porous BN.

PMID- 27687247
TI  - Corrigendum: Novel technique to suppress hydrocarbon contamination for high
      accuracy determination of carbon content in steel by FE-EPMA.

PMID- 27687249
TI  - Dichotomy of cellular inhibition by small-molecule inhibitors revealed by single
      cell analysis.
AB  - Despite progress in drug development, a quantitative and physiological
      understanding of how small-molecule inhibitors act on cells is lacking. Here, we
      measure the signalling and proliferative response of individual primary T
      lymphocytes to a combination of antigen, cytokine and drug. We uncover two
      distinct modes of signalling inhibition: digital inhibition (the activated
      fraction of cells diminishes upon drug treatment, but active cells appear
      unperturbed), versus analogue inhibition (the activated fraction is unperturbed
      whereas activation response is diminished). We introduce a computational model of
      the signalling cascade that accounts for such inhibition dichotomy, and test the
      model predictions for the phenotypic variability of cellular responses. Finally,
      we demonstrate that the digital/analogue dichotomy of cellular response as
      revealed on short (signal transduction) timescales, translates into similar
      dichotomy on longer (proliferation) timescales. Our single-cell analysis of drug
      action illustrates the strength of quantitative approaches to translate in vitro
      pharmacology into functionally relevant cellular settings.

PMID- 27687248
TI  - Low expression of galectin-3 is associated with poor survival in node-positive
      breast cancers and mesenchymal phenotype in breast cancer stem cells.
AB  - BACKGROUND: Galectin-3 (Gal3) plays diverse roles in cancer initiation,
      progression, and drug resistance depending on tumor type characteristics that are
      also associated with cancer stem cells (CSCs). Recurrence of breast carcinomas
      may be attributed to the presence of breast CSCs (BCSCs). BCSCs exist in
      mesenchymal-like or epithelial-like states and the transition between these
      states endows BCSCs with the capacity for tumor progression. The discovery of a
      feedback loop with galectins during epithelial-to-mesenchymal transition (EMT)
      prompted us to investigate its role in breast cancer stemness. METHOD: To
      elucidate the role of Gal3 in BCSCs, we performed various in vitro and in vivo
      studies such as sphere-formation assays, Western blotting, flow cytometric
      apoptosis assays, and limited dilution xenotransplant models. Histological
      staining for Gal3 in tissue microarrays of breast cancer patients was performed
      to analyze the relationship of clinical outcome and Gal3 expression. RESULTS:
      Here, we show in a cohort of 87 node-positive breast cancer patients treated with
      doxorubicin-based chemotherapy that low Gal3 was associated with increased
      lymphovascular invasion and reduced overall survival. Analysis of in vitro BCSC
      models demonstrated that Gal3 knockdown by small hairpin RNA (shRNA) interference
      in epithelial-like mammary spheres leads to EMT, increased sphere-formation
      ability, drug-resistance, and heightened aldefluor activity. Furthermore,
      Gal3negative BCSCs were associated with enhanced tumorigenicity in orthotopic
      mouse models. CONCLUSIONS: Thus, in at least some breast cancers, loss of Gal3
      might be associated with EMT and cancer stemness-associated traits, predicts poor
      response to chemotherapy, and poor prognosis.

PMID- 27687251
TI  - Fully automated structural MRI of the brain in clinical dementia workup.
AB  - Background The dementia syndrome has been regarded a clinical diagnosis but the
      focus on supplemental biomarkers is increasing. An automatic magnetic resonance
      imaging (MRI) volumetry method, NeuroQuant(r) (NQ), has been developed for use in
      clinical settings. Purpose To evaluate the clinical usefulness of NQ in
      distinguishing Alzheimer's disease dementia (AD) from non-dementia and non-AD
      dementia. Material and Methods NQ was performed in 275 patients diagnosed
      according to the criteria of ICD-10 for AD, vascular dementia and Parkinson's
      disease dementia (PDD); the Winblad criteria for mild cognitive impairment; the
      Lund-Manchester criteria for frontotemporal dementia; and the revised consensus
      criteria for Lewy body dementia (LBD). Receiver operating curve (ROC) analyses
      with calculation of area under the curve (AUC) and regression analyses were
      carried out. Results Forebrain parenchyma (AUC 0.82), hippocampus (AUC 0.80), and
      inferior lateral ventricles (AUC 0.78) yielded the highest AUCs for AD/non
      dementia discrimination. Only hippocampus (AUC 0.62) and cerebellum (AUC 0.67)
      separated AD from non-AD dementia. Cerebellum separated AD from PDD-LBD (AUC
      0.83). Separate multiple regression analyses adjusted for age and gender, showed
      that memory (CERAD 10-word delayed recall) (beta 0.502, P < 0.001) was more
      strongly associated to the hippocampus volume than the diagnostic distinction of
      AD versus non-dementia (beta -0.392, P < 0.001). Conclusion NQ measures could
      separate AD from non-dementia fairly well but generally poorer from non-AD
      dementia. Degree of memory impairment, age, and gender, but not diagnostic
      distinction, were associated to the hippocampus volume in adjusted analyses.
      Surprisingly, cerebellum was found relevant in separating AD from PDD-LBD.

PMID- 27687250
TI  - Simultaneous Quantification of Serum Nonesterified and Esterified Fatty Acids as
      Potential Biomarkers to Differentiate Benign Lung Diseases from Lung Cancer.
AB  - In this study, we have employed graphene oxide as a matrix to simultaneously and
      directly quantify serum nonesterified and esterified fatty acids (FAs) using
      matrix-assisted laser/desorption ionization-Fourier transform ion cyclotron
      resonance mass spectrometry (MALDI-FTICR MS). Twelve serum nonesterified FAs
      combined with their individual esterified FAs (i.e., C16:0, C16:1, C18:0, C18:1,
      C18:2, C18:3, C20:2, C20:3, C20:4, C20:5, C22:5, and C22:6) were quantified based
      on their calibration curves with the correlation coefficients of >0.99, along
      with the analytical time of <1 min each sample. As a result, serum levels of
      twelve total FAs (TFAs) in 1440 serum samples from 487 healthy controls (HCs),
      479 patients with benign lung diseases (BLDs) and 474 patients with lung cancer
      (LC) were determined. Statistical analysis indicated that significantly increased
      levels of C16:0, C16:1, C18:0, C18:1, C18:3, C20:3, and C22:6 and decreased
      levels of C20:5 were observed in LC patients compared with BLDs. Receiver
      operating characteristic (ROC) analysis revealed that panel a (C18:2, C20:3,
      C20:4, C20:5, C22:5, and C22:6), panel b (C18:0, C20:4, C20:5, and C22:6), and
      panel c (C16:1, C18:0, C18:1, C20:3, and C22:6) have exhibited good diagnostic
      ability to differentiate BLDs from LC relative to clinical uses of tumor markers
      (CEA and Cyfra 21-1).

PMID- 27687252
TI  - Overlapping self-expandable metallic stent for palliation of a long (>10 cm)
      malignant gastroduodenal obstruction.
AB  - Background Self-expandable metallic stent (SEMS) placement is a well-established
      palliative treatment approach for malignant gastroduodenal obstruction. In
      patients with a long (>10 cm) stricture, multiple stents placed in an overlapping
      fashion are often required. Purpose To investigate the outcomes of overlapping
      SEMS placement for the palliative treatment of malignant gastroduodenal
      obstruction in patients with a long (>10 cm) stricture. Material and Methods The
      medical records of 40 patients who underwent fluoroscopic overlapping SEMS
      placement for malignant gastroduodenal obstruction due to a long (>10 cm)
      stricture were reviewed. Results The technical and clinical success rates were
      100% and 65.0%, respectively. The mean length of the stricture was 17.0 +/- 4.7
      cm and the mean number of stents placed in each patient was 2.2 +/- 0.5.
      Metastatic cancer (odds ratio [OR], 0.315; P = 0.018), Eastern Cooperative
      Oncology Group (ECOG) score >=3 (OR, 0.018; P = 0.006), and carcinomatosis with
      ascites (OR, 0.025; P = 0.017) were independent predictors of poor clinical
      success. The rates of minor and major complications were 27.5% and 2.5%,
      respectively. The median stent patency and survival were 33 days (interquartile
      range [IQR], 19-60 days) and 35 days (IQR, 19-73 days), respectively. An ECOG
      score >=3 was an independent predictor of a poor survival outcome (hazard ratio,
      4.681; P < 0.001). Conclusion Overlapping SEMS placement may be safe and
      effective for the palliative treatment of malignant gastroduodenal obstruction in
      patients with a long (>10 cm) stricture.

PMID- 27687253
TI  - Polymorphism rs7555523 in transmembrane and coiled-coil domain 1 (TMCO1) is not a
      risk factor for primary open angle glaucoma in a Saudi cohort.
AB  - BACKGROUND: We investigated whether polymorphism rs7555523 (A > C) in human
      transmembrane and coiled-coil domain 1 (TMCO1) gene is a risk factor for primary
      open angle glaucoma (POAG) in a Saudi cohort. METHODS: A cohort of 87 unrelated
      POAG cases and 94 control subjects from Saudi Arabia were genotyped using Taq
      Man(r) assay. The association of genotypes with POAG and other glaucoma specific
      clinical indices was investigated. RESULTS: The genotype and allele frequency of
      polymorphism rs7555523 at TMCO1 did not show any statistically significant
      association with POAG as compared to controls. The minor allele frequency was
      0.103 in cases and 0.085 in controls. Except for awareness of glaucoma (p =
      0.036), no significant association of genotypes were seen with glaucoma specific
      clinical indices such as intraocular pressure (IOP), cup/disc ratio and number of
      anti-glaucoma medications used. Binary logistic regression analysis (adjusted for
      age and gender) showed that age was a significant indicator for the development
      of glaucoma in this group (adjusted odds ratio = 1.2; 95 % confidence interval =
      1.078-1.157; p < 0.001). CONCLUSION: Our study was unable to replicate the
      findings of previously reported association for polymorphism rs7555523 in TMCO1
      with POAG and related clinical indices such as IOP and cup/disc ratio indicating
      that this variant is not a risk factor for POAG in the Saudi cohort.

PMID- 27687255
TI  - Treatment of hookworm-related cutaneous larva migrans with topical ivermectin.

PMID- 27687254
TI  - Integrins as architects of cell behavior.
AB  - Integrins are cell surface receptors that bind cells to their physical external
      environment, linking the extracellular matrix to cell function. They are
      essential in the biology of all animals. In the late 1980s, we discovered that
      integrins are required for the ability of breast epithelia to do what they are
      programmed to do, which is to differentiate and make milk. Since then, integrins
      have been shown to control most other aspects of phenotype: to stay alive, to
      divide, and to move about. Integrins also provide part of the mechanism that
      allows cells to form tissues. Here I discuss how we discovered that integrins
      control mammary gland differentiation and explore the role of integrins as
      central architects of other aspects of cell behavior.

PMID- 27687256
TI  - Chemical composition of Melicope belahe (Baill.) T. G. Hartley (Rutaceae) leaf
      essential oil from Madagascar.
AB  - Melicope belahe (Baill.) T.G. Hartley (Rutaceae) is an endemic species to
      Madagascar. The chemical composition of leaf essential oil is reported for the
      first time. A sample was extracted by hydrodistillation and analysis was carried
      out by combination of chromatographic (GC), spectroscopic and spectrometric (MS,
      13C NMR) techniques. In total, 56 compounds have been identified. The chemical
      composition was dominated by alpha-pinene (42.6%) followed by linalool (6.2%) and
      (E)-beta-caryophyllene (5.2%).

PMID- 27687257
TI  - Topoisomerases: Resistance versus Sensitivity, How Far We Can Go?
AB  - DNA topoisomerases are ubiquitously present remarkable molecular machines that
      help in altering topology of DNA in living cells. The crucial role played by
      these nucleases during DNA replication, transcription, and recombination vis-a
      vis less sequence similarity among different species makes topoisomerases unique
      and attractive targets for different anticancer and antibacterial drugs. However,
      druggability of topoisomerases by the existing class of molecules is increasingly
      becoming questationable due to resistance development predominated by mutations
      in the corresponding genes. The current scenario facing a decline in the
      development of new molecules further comprises an important factor that may
      challenge topoisomerase-targeting therapy. Thus, it is imperative to wisely use
      the existing inhibitors lest with this rapid rate of losing grip over the target
      we may not go too far. Furthermore, it is important not only to design new
      molecules but also to develop new approaches that may avoid obstacles in
      therapies due to multiple resistance mechanisms. This review provides a succinct
      account of different classes of topoisomerase inhibitors, focuses on resistance
      acquired by mutations in topoisomerases, and discusses the various approaches to
      increase the efficacy of topoisomerase inhibitors. In a later section, we also
      suggest the possibility of using bisbenzimidazoles along with efflux pump
      inhibitors for synergistic bactericidal effects.

PMID- 27687258
TI  - Can lessons from systems-based mastery learning for thoracentesis be translated
      to hospitalists?

PMID- 27687262
TI  - Antimicrobial resistance: UN endorses a One Health approach.

PMID- 27687259
TI  - Spontaneous pneumothorax in paracoccidioidomycosis patients from an endemic area
      in Midwestern Brazil.
AB  - Paracoccidioidomycosis (PCM) is the most important systemic mycosis in Latin
      America. About 80% of PCM patients are present with its chronic form. The lungs
      are affected in most patients with the chronic form; however, pleural involvement
      has rarely been reported. We describe nine cases of PCM that presented with lung
      involvement and spontaneous pneumothorax. All patients, except one whose
      condition was not investigated, were smokers. PCM was diagnosed during the
      pneumothorax episode in three patients, and from 3 to 16 years before the
      pneumothorax episode in six patients. A total of six patients underwent chest
      drainage and one died as a direct result of the pneumothorax. We suggest that
      pneumothorax, although rare, should be considered in PCM patients who present
      with suddenly worsening dyspnoea. PCM should also be investigated in cases of
      pneumothorax in adult men from mycosis-endemic areas.

PMID- 27687265
TI  - Looking out and looking in at BVA Members' Day.

PMID- 27687267
TI  - Vectorborne diseases: no respecters of borders.
AB  - Vectorborne diseases have been very much in the news in 2016, with, for example,
      the outbreak of Zika virus resulting in a number of high-profile athletes
      withdrawing from this year's Olympic Games in Brazil. In the UK, the threat of
      bluetongue virus arriving by windborne midges from France remains real. In his
      latest update for Veterinary Record, Nigel Gibbens, the UK's Chief Veterinary
      Officer, discusses why a collaborative approach is needed to combat such diseases
      and their vectors. 

PMID- 27687269
TI  - Veterinary medicines update.
AB  - The following information has been produced for Veterinary Record by the
      Veterinary Medicines Directorate (VMD) to provide an update for veterinary
      surgeons on recent changes to marketing authorisations for veterinary medicines
      in the UK and on other relevant issues. 

PMID- 27687270
TI  - Disease surveillance in England and Wales, September 2016.
AB  - ? Current and emerging issues? Highlights from the scanning surveillance network?
      Update on international disease threats? Cattle respiratory disease in late
      summer and autumnThese are among matters discussed in the Animal and Plant Health
      Agency's (APHA's) September disease surveillance report. 

PMID- 27687271
TI  - Cattle respiratory disease in late summer and autumn.
AB  - Increased diagnoses of husk in cattle are seen as summer turns into autumn. In
      this article, Arthur Otter of the APHA Cattle Expert Group discusses how the
      disease is diagnosed, and other respiratory diseases that it might be confused
      with. 

PMID- 27687272
TI  - Selecting the right antimicrobial for use in pet species.

PMID- 27687274
TI  - Use of veterinary medicines in farm animals.

PMID- 27687273
TI  - Battery ingestion in dogs.

PMID- 27687275
TI  - Correction.

PMID- 27687276
TI  - Meet the new BVA President, Gudrun Ravetz.
AB  - Gudrun Ravetz became BVA President for 2016/17 at BVA Members' Day on September
      22. Here, she looks to the year ahead. 

PMID- 27687277
TI  - Close encounters with BVA at London Vet Show.
AB  - Close encounters of the animal and human kind will be the focus of Christine
      Nicol's Wooldridge Memorial Lecture at this year's BVA Congress. BVA media
      manager Shirley Dent explains. 

PMID- 27687278
TI  - International virtual congress.
AB  - BVA's partner, The Webinar Vet, has announced the line-up for its 24-hour
      International Webinar Vet Virtual Congress 2017, which starts at midnight on
      January 20. 

PMID- 27687279
TI  - BVA pledges support for rabies campaign.
AB  - BVA has announced its support for a campaign to end human deaths from canine
      mediated rabies by 2030. BVA policy officer Susie Child explains. 

PMID- 27687280
TI  - The benefits of joining your local YVN group.
AB  - Becky Marr, one of the recent graduate representatives on BVA Council, encourages
      new and recent graduates to get involved with the Young Vet Network. 

PMID- 27687282
TI  - New YVN groups.
AB  - Young Vet Network (YVN) groups provide local peer support. Tim Keen, BVA's
      relationship marketing manager, gives an update. 

PMID- 27687281
TI  - Addressing issues in Scotland.
AB  - Ofordi Nabokei, interim head of policy and governance, reports on last month's
      annual BVA Scottish dinner and on working with BVA Scottish Branch. 

PMID- 27687283
TI  - Mentoring for new graduates.
AB  - The School of Veterinary Medicine in Dublin (UCD) has introduced an alumni
      mentoring programme for new veterinary and veterinary nursing graduates. Helen
      Graham, clinical education support manager, explains how it works. 

PMID- 27687284
TI  - Ten-minute chat.
AB  - During her first degree, Jess French founded a programme in which university
      students taught primary school children about environmental issues. She recently
      qualified as a vet and, when not studying, teaching, writing or looking for bugs,
      she enjoys adventure sports and travel, learning new languages and playing the
      saxophone and drums. She is also a presenter on CBeebies. 

PMID- 27687285
TI  - Interpreter training for medical students: pilot implementation and assessment in
      a student-run clinic.
AB  - BACKGROUND: Trained medical interpreters are instrumental to patient satisfaction
      and quality of care. They are especially important in student-run clinics, where
      many patients have limited English proficiency. Because student-run clinics have
      ties to their medical schools, they have access to bilingual students who may
      volunteer to interpret, but are not necessarily formally trained. METHODS: To
      study the feasibility and efficacy of leveraging medical student volunteers to
      improve interpretation services, we performed a pilot study at the student-run
      clinic at the Icahn School of Medicine at Mount Sinai. In each fall semester in
      2012-2015, we implemented a 6-h course providing didactic and interactive
      training on medical Spanish interpreting techniques and language skills to
      bilingual students. We then assessed the impact of the course on interpreter
      abilities. RESULTS: Participants' comfort levels, understanding of their roles,
      and understanding of terminology significantly increased after the course (p <
      0.05), and these gains remained several months later (p < 0.05) and were repeated
      in an independent cohort. Patients and student clinicians also rated participants
      highly (averages above 4.5 out of 5) on these measures in real clinical
      encounters. CONCLUSIONS: These findings suggest that a formal interpreter
      training course tailored for medical students in the setting of a student-run
      clinic is feasible and effective. This program for training qualified student
      interpreters can serve as a model for other settings where medical students serve
      as interpreters.

PMID- 27687286
TI  - Distribution and Diversity of Microbial Eukaryotes in Bathypelagic Waters of the
      South China Sea.
AB  - Little is known about the biodiversity of microbial eukaryotes in the South China
      Sea, especially in waters at bathyal depths. Here, we employed SSU rDNA gene
      sequencing to reveal the diversity and community structure across depth and
      distance gradients in the South China Sea. Vertically, the highest alpha
      diversity was found at 75-m depth. The communities of microbial eukaryotes were
      clustered into shallow-, middle-, and deep-water groups according to the depth
      from which they were collected, indicating a depth-related diversity and
      distribution pattern. Rhizaria sequences dominated the microeukaryote community
      and occurred in all samples except those from less than 50-m deep, being most
      abundant near the sea floor where they contributed ca. 64-97% and 40-74% of the
      total sequences and OTUs recovered, respectively. A large portion of rhizarian
      OTUs has neither a nearest named neighbor nor a nearest neighbor in the GenBank
      database which indicated the presence of new phylotypes in the South China Sea.
      Given their overwhelming abundance and richness, further phylogenetic analysis of
      rhizarians were performed and three new genetic clusters were revealed containing
      sequences retrieved from the deep waters of the South China Sea. Our results shed
      light on the diversity and community structure of microbial eukaryotes in this
      not yet fully explored area.

PMID- 27687287
TI  - Taking OSCE examiner training on the road: reaching the masses.
AB  - BACKGROUND: To ensure the rigour of objective structured clinical examinations
      (OSCEs) in assessing medical students, medical school educators must educate
      examiners with a view to standardising examiner assessment behaviour. Delivering
      OSCE examiner training is a necessary yet challenging part of the OSCE process. A
      novel approach to implementing training for current and potential OSCE examiners
      was trialled by delivering large-group education sessions at major teaching
      hospitals. METHODS: The 'OSCE Roadshow' comprised a short training session
      delivered in the context of teaching hospital 'Grand Rounds' to current and
      potential OSCE examiners. The training was developed to educate clinicians about
      OSCE processes, clarify the examiners' role and required behaviours, and to
      review marking guides and mark allocation in an effort to standardise OSCE
      processes and encourage consistency in examiner marking behaviour. A short
      exercise allowed participants to practise marking a mock OSCE to investigate
      examiner marking behaviour after the training. RESULTS: OSCE Roadshows at four
      metropolitan and one rural teaching hospital were well received and well attended
      by 171 clinicians across six sessions. Unexpectedly, medical students also
      attended in large numbers (n=220). After training, participants' average scores
      for the mock OSCE clustered closely around the ideal score of 28 (out of 40), and
      the average scores did not differ according to the levels of clinical experience.
      CONCLUSION: The OSCE Roadshow demonstrated the potential of brief familiarisation
      training in reaching large numbers of current and potential OSCE examiners in a
      time and cost-effective manner to promote standardisation of OSCE processes.

PMID- 27687288
TI  - High genetic diversity and population differentiation in Clarias gariepinus of
      Yala Swamp: evidence from mitochondrial DNA sequences.
AB  - In order to improve the conservation and sustainable utilization of the African
      catfish Clarias gariepinus of the Yala Swamp in Kenya, genetic diversity and
      population structure of Lakes Kanyaboli and Namboyo populations of the species
      were studied using DNA sequences of the mitochondrial D-loop control region.
      Genetic diversity inferred as haplotype and nucleotide diversities and number of
      singletons and shared haplotypes was higher in the Lake Kanyaboli population
      (LKG) than the Lake Namboyo population (LNG) of C. gariepinus. Thirty-one
      haplotypes were inferred, of which 25 (80.6%) were private or singletons, while
      only six (19.4%) haplotypes were shared between LKG and LNG. Both populations
      were differentiated, with FST value that was significantly different from zero (P
      < 0.05). Two clusters were inferred both from the maximum likelihood tree and the
      spanning networks of phylogenetic relationships of haplotypes. Mismatch
      distribution for total sample was multi-modal but individually, distributions
      were uni-modal in LKG, but multimodal in LNG. The mean +/- s.d. raggedness index
      for both populations was 0.085 +/- 0.098 and not significantly different from
      zero (P > 0.05). Individual raggedness indices were 0.015 and 0.154 for LKG and
      LNG respectively. Fu's Fs was negative for both populations, with LKG recording 
      14.871, while LNG had -2.565, significantly different from zero for LKG (P <
      0.05), but the value for LNG was not significant (P > 0.05). Tajima's D was
      negative for both populations, with LKG recording -1.734, while LNG had -1.136.
      Standardized square differences (SSD) were 0.001 for LKG and 0.048 for LNG and
      non-significant between them (P > 0.05). Values between all populations were also
      not significantly different (P > 0.05), mean +/- s.d. SSD 0.025 +/- 0.033.

PMID- 27687289
TI  - Progression of motor neuron disease is accelerated and the ability to recover is
      compromised with advanced age in rNLS8 mice.
AB  - In order to treat progressive paralysis in ALS patients, it is critical to
      develop a mouse that closely models human ALS in both pathology and also in the
      timing of these events. We have recently generated new TDP-43 bigenic mice
      (called rNLS8) with doxycycline (Dox)-suppressible expression of human TDP-43
      (hTDP-43) harboring a defective nuclear localization signal (hTDP-43?NLS) under
      the control of the NEFH promoter. Our previous studies characterized the
      pathology and disease course in young rNLS8 mice following induction of neuronal
      hTDP-43DeltaNLS. We now seek to examine if the order and timing of pathologic
      events are changed in aged mice. We found that the expression of hTDP-43?NLS in
      12+ month old mice did not accelerate the appearance of neuromuscular
      abnormalities or motor neuron (MN) death in the lumbar spinal cord (SC), though
      disease progression was accelerated. However, following suppression of the
      transgene, important differences between young and aged rNLS8 mice emerged in
      functional motor recovery. We found that recovery was incomplete in aged mice
      relative to their younger treatment matched counterparts based on gross
      behavioral measures and physiological recordings from the animals' gastrocnemius
      (GC) muscles, despite muscle reinnervation by surviving MNs. This is likely
      because the reinnervation most often only resulted in partial nerve and endplate
      connections and the muscle's junctional folds were much more disorganized in aged
      rNLS8 mice. We believe that these studies will be an important basis for the
      future design and evaluation of therapies designed to slow denervation and
      promote re-innervation in adult ALS patients.

PMID- 27687290
TI  - Calendaring and alarms can improve naturalistic time-based prospective memory for
      youth infected with HIV.
AB  - Individuals with HIV disease often evidence deficits in prospective memory (PM),
      which interfere with daily functioning and increase the risk of suboptimal health
      behaviours. This study examined the benefits of simple encoding and cueing
      supports on naturalistic time-based PM in 47 HIV-positive young adults. All
      participants completed a naturalistic time-based PM task in which they were
      instructed to text the examiner once per day for seven days at a specified time.
      Participants were randomised into (1) a Calendaring condition in which they
      created a calendar event in their mobile telephone for the specified texting
      time; (2) an Alarm condition in which they programmed an alarm into their mobile
      telephone for the specified texting time; (3) a Combined calendaring and alarm
      condition; and (4) a Control condition. Participants in the Combined condition
      demonstrated significantly better naturalistic PM performance than participants
      in the Control and Calendaring conditions. Findings indicate that HIV-positive
      young people may benefit from a combined calendaring and alarm supportive
      strategy for successful execution of future intentions in daily life.

PMID- 27687292
TI  - Decision-making in rectal and colorectal cancer: systematic review and
      qualitative analysis of surgeons' preferences.
AB  - Surgeons are experiencing difficulties implementing recommendations not only
      owing to incomplete, confusing or conflicting information but also to the
      increasing involvement of patients in decisions relating to their health. This
      study sought to establish which common factors including heuristic factors guide
      surgeons' decision-making in colon and rectal cancers. We conducted a systematic
      literature review of surgeons' decision-making factors related to colon and
      rectal cancer treatment. Eleven of 349 identified publications were eligible for
      data analyses. Using the IRaMuTeQ (Interface of R for the Multidimensional
      Analyses of Texts and Questionnaire), we carried out a qualitative analysis of
      the significant factors collected in the studies reviewed. Several validation
      procedures were applied to control the robustness of the findings. Five
      categories of factors (i.e. patient, surgeon, treatment, tumor and organizational
      cues) were found to influence surgeons' decision-making. Specifically, all
      decision criteria including biomedical (e.g. tumor information) and heuristic
      (e.g. surgeons' dispositional factors) criteria converged towards the factor 'age
      of patient' in the similarity analysis. In the light of the results, we propose
      an explanatory model showing the impact of heuristic criteria on medical issues
      (i.e. diagnosis, prognosis, treatment features, etc.) and thus on decision
      making. Finally, the psychosocial complexity involved in decision-making is
      discussed and a medico-psycho-social grid for use in multidisciplinary meetings
      is proposed.

PMID- 27687291
TI  - Transcriptomic regulations in oligodendroglial and microglial cells related to
      brain damage following fetal growth restriction.
AB  - Fetal growth restriction (FGR) is a major complication of human pregnancy,
      frequently resulting from placental vascular diseases and prenatal malnutrition,
      and is associated with adverse neurocognitive outcomes throughout life. However,
      the mechanisms linking poor fetal growth and neurocognitive impairment are
      unclear. Here, we aimed to correlate changes in gene expression induced by FGR in
      rats and abnormal cerebral white matter maturation, brain microstructure, and
      cortical connectivity in vivo. We investigated a model of FGR induced by low
      protein-diet malnutrition between embryonic day 0 and birth using an
      interdisciplinary approach combining advanced brain imaging, in vivo
      connectivity, microarray analysis of sorted oligodendroglial and microglial cells
      and histology. We show that myelination and brain function are both significantly
      altered in our model of FGR. These alterations, detected first in the white
      matter on magnetic resonance imaging significantly reduced cortical connectivity
      as assessed by ultrafast ultrasound imaging. Fetal growth retardation was found
      associated with white matter dysmaturation as shown by the immunohistochemical
      profiles and microarrays analyses. Strikingly, transcriptomic and gene network
      analyses reveal not only a myelination deficit in growth-restricted pups, but
      also the extensive deregulation of genes controlling neuroinflammation and the
      cell cycle in both oligodendrocytes and microglia. Our findings shed new light on
      the cellular and gene regulatory mechanisms mediating brain structural and
      functional defects in malnutrition-induced FGR, and suggest, for the first time,
      a neuroinflammatory basis for the poor neurocognitive outcome observed in growth
      restricted human infants. GLIA 2016;64:2306-2320.

PMID- 27687293
TI  - Real-time MRI of swallowing: intraoral pressure reduction supports larynx
      elevation.
AB  - The reduction in intraoral pressure during swallowing has previously been linked
      to bolus transport, although no such relation has yet been proven. The purpose of
      this work was to evaluate the time course of intraoral pressure during swallowing
      using simultaneous real-time magnetic resonance imaging (MRI) and dynamic
      pressure recordings. Real-time MRI based on highly undersampled radial fast low
      angle shot (FLASH) and regularized nonlinear inverse reconstruction was performed
      at 3 T using a standard head coil and a mid-sagittal section covering the entire
      oral cavity. Voluntary swallowing (10 mL of pineapple juice or saliva) was
      monitored for about 30 s in 11 normal subjects at spatial and temporal resolution
      of 1.3 * 1.3 * 8 mm3 and 40 ms, respectively. Simultaneously, the intraoral
      atmospheric pressure was recorded at a resolution of 10 ms during the entire
      course of deglutition. Quantitative measures of bolus transport, larynx elevation
      and submental muscle changes were obtained from the image series. As a key
      result, negative intraoral pressure accompanied laryngeal elevation during
      swallowing in all subjects. A reduction in submental muscle length during
      swallowing was also observed. No correlations of maximum negative pressure with
      larynx elevation and submental muscle change were found. In conclusion, intraoral
      pressure reduction during swallowing is not connected to oral bolus transport,
      but supports laryngeal elevation by palatal fixation of the tongue.

PMID- 27687294
TI  - The influence of the menstrual cycle on reactivity to a CO2 challenge among women
      with and without premenstrual symptoms.
AB  - Clinically significant premenstrual symptoms (PMS) is conceptualized as a
      depressive disorder in DSM-5, however, it may share pathophysiological processes
      with anxiety- and fear-related disorders. Specifically, women with PMS panic at
      higher rates during biological challenge procedures. It is unclear if this
      increased interoceptive sensitivity is a general vulnerability or specific to the
      premenstrual phase. The current study examined the role of menstrual cycle phase
      on reactivity to a CO2 challenge among women with (n = 11) and without (n = 26)
      clinically significant PMS (N = 37). During the late follicular phase (days 6
      12), women with and without PMS responded similarly to the CO2 challenge, whereas
      during the premenstrual phase (within 5 days before menses), women with PMS
      reported significantly more intense panic symptoms in response to the challenge
      than women without PMS. Vulnerability to panic in women with PMS may be specific
      to the premenstrual phase. Potential psychological and neurobiological mechanisms
      underlying this phenomenon are discussed.

PMID- 27687295
TI  - Decision making about Pap test use among Korean immigrant women: A qualitative
      study.
AB  - BACKGROUND: Understanding how individuals make decisions about Pap tests
      concerning their personal values helps health-care providers offer tailored
      approaches to guide patients' decision making. Yet research has largely ignored
      decision making about Pap tests among immigrant women who experience increased
      risk of cervical cancer. OBJECTIVE: To explore decision making about Pap tests
      among Korean immigrant women. METHODS: We conducted a qualitative descriptive
      study using 32 semi-structured, in-depth interviews with Korean immigrant women
      residing in a north-eastern metropolitan area. Data were audio-recorded,
      transcribed verbatim and analysed using inductive coding. RESULTS: Although most
      women with positive decisions made their own decisions, some women deferred to
      their providers, and others made decisions in collaboration with their providers
      and significant others. While women making positive decisions tended to consider
      both barriers to and facilitators of having Pap tests, women making negative
      decisions predominantly discussed the barriers to having Pap tests, such as
      modesty and differences between the South Korean and US health-care systems. The
      women's reflections on their decisions differed regarding their Pap test
      decisions. CONCLUSIONS: Women's desired roles in the decision-making process and
      reflection on their decision outcome appeared to vary, although most participants
      with positive decisions made their own decisions and were satisfied with their
      decisions. Future research should conduct longitudinal, quantitative studies to
      test our findings regarding decision-making processes and outcomes about Pap
      tests. IMPLICATIONS: The findings should be incorporated into cervical cancer
      screening practices to fulfil the unmet needs of immigrant women in patient
      provider communication and to facilitate women's decision making about Pap tests.

PMID- 27687296
TI  - Phytoestrogens and risk of prostate cancer: an updated meta-analysis of
      epidemiologic studies.
AB  - This updated meta-analysis was performed to clarify the relationship between
      phytoestrogens and prostate cancer risk. Twenty one case-control and two cohort
      studies were finally selected for this meta-analysis, totaling 11,346 cases and
      140,177 controls. Analytical results showed that daidzein (OR = 0.85; 95% CI:
      0.75-0.96), genistein (OR = 0.87; 95% CI: 0.78-0.98), and glycitein (OR = 0.89;
      95% CI: 0.81-0.98) were associated with a reduction of prostate cancer risk, but
      total isoflavones (OR = 0.93; 95% CI: 0.84-1.04), equol (OR = 0.86; 95% CI: 0.66
      1.14), total lignans (OROgna.05; 95% CI: 0.54-2.04), secoisolariciresinol (OR =
      1.02; 95% CI: 0.83-1.24), matairesinol (OR = 0.91; 95% CI: 0.75-1.11),
      enterolactone (OR = 0.94; 95% CI: 0.73-1.20), and coumestrol (OR = 0.89; 95% CI:
      0.76-1.06) were not. Sensitivity and publication bias analyses demonstrated that
      the pooled estimates were stable and reliable. The results support the notion
      that some phytoestrogens may have a role in decreasing the risk of prostate
      cancer. Additional large and well-designed cohort studies are needed to confirm
      these relationships.

PMID- 27687297
TI  - Recombinant flavin-dependent halogenases are functional in tobacco chloroplasts
      without co-expression of flavin reductase genes.
AB  - Halogenation of natural compounds in planta is rare. Herein, a successful
      engineering of tryptophan 6-halogenation into the plant context by heterologous
      expression of the Streptomyces toxytricini Stth gene and localization of its
      enzymatic product in various tobacco cell compartments is described. When co
      expressed with the flavin reductase rebF from Lechevalieria aerocolonigenes, Stth
      efficiently produced chlorinated tryptophan in the cytosol. Further,
      supplementation of KBr yielded the brominated metabolite. More strikingly,
      targeting of the protein to the chloroplasts enabled effective halogenation of
      tryptophan even in absence of the partner reductase, providing crucial evidence
      for sufficient, organelle-specific supply of the FADH2 cofactor to drive halogen
      integration. Incorporation of an alternative enzyme, the 7-halogenase RebH from
      L. aerocolonigenes, into the metabolic set-up resulted in the formation of 6,7
      dichlorotryptophan. Finally, expression of tryptophan decarboxylase (tdc) in
      concert with stth led to the generation of 6-chlorotryptamine, a new-to-nature
      precursor of monoterpenoid indole alkaloids. In sum, the report highlights the
      tremendous application potential of plants as a unique chassis for the
      engineering of rare and valuable halogenated natural products, with chloroplasts
      as the cache of reduction equivalents driving metabolic reactions.

PMID- 27687298
TI  - Pre-steady state kinetics of DNA binding and abasic site hydrolysis by tyrosyl
      DNA phosphodiesterase 1.
AB  - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) processes DNA 3'-end-blocking
      modifications, possesses DNA and RNA 3'-nucleosidase activity and is also able to
      hydrolyze an internal apurinic/apyrimidinic (AP) site and its synthetic analogs.
      The mechanism of Tdp1 interaction with DNA was analyzed using pre-steady state
      stopped-flow kinetics with tryptophan, 2-aminopurine and Forster resonance energy
      transfer fluorescence detection. Phosphorothioate or tetramethyl phosphoryl
      guanidine groups at the 3'-end of DNA have been used to prevent 3'-nucleosidase
      digestion by Tdp1. DNA binding and catalytic properties of Tdp1 and its mutants
      H493R (Tdp1 mutant SCAN1) and H263A have been compared. The data indicate that
      the initial step of Tdp1 interaction with DNA includes binding of Tdp1 to the DNA
      ends followed by the 3'-nucleosidase reaction. In the case of DNA containing AP
      site, three steps of fluorescence variation were detected that characterize (i)
      initial binding the enzyme to the termini of DNA, (ii) the conformational
      transitions of Tdp1 and (iii) search for and recognition of the AP-site in DNA,
      which leads to the formation of the catalytically active complex and to the AP
      site cleavage reaction. Analysis of Tdp1 interaction with single- and double
      stranded DNA substrates shows that the rates of the 3'-nucleosidase and AP-site
      cleavage reactions have similar values in the case of single-stranded DNA,
      whereas in double-stranded DNA, the cleavage of the AP-site proceeds two times
      faster than 3'-nucleosidase digestion. Therefore, the data show that the AP-site
      cleavage reaction is an essential function of Tdp1 which may comprise an
      independent of AP endonuclease 1 AP-site repair pathway.

PMID- 27687299
TI  - Foreword.

PMID- 27687301
TI  - The diabetic foot.

PMID- 27687305
TI  - Is the routine use of trimodality therapy for selected patients with non-small
      cell lung cancer supported by long-term clinical outcomes?

PMID- 27687304
TI  - Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune
      disorders or major toxicity with ipilimumab.
AB  - Background: Anti-PD-1 antibodies (anti-PD-1) have clinical activity in a number
      of malignancies. All clinical trials have excluded patients with significant
      preexisting autoimmune disorders (ADs) and only one has included patients with
      immune-related adverse events (irAEs) with ipilimumab. We sought to explore the
      safety and efficacy of anti-PD-1 in such patients. Patients and methods: Patients
      with advanced melanoma and preexisting ADs and/or major immune-related adverse
      events (irAEs) with ipilimumab (requiring systemic immunosuppression) that were
      treated with anti-PD-1 between 1 July 2012 and 30 September 2015 were
      retrospectively identified. Results: One hundred and nineteen patients from 13
      academic tertiary referral centers were treated with anti-PD-1. In patients with
      preexisting AD (N = 52), the response rate was 33%. 20 (38%) patients had a flare
      of AD requiring immunosuppression, including 7/13 with rheumatoid arthritis, 3/3
      with polymyalgia rheumatica, 2/2 with Sjogren's syndrome, 2/2 with immune
      thrombocytopaenic purpura and 3/8 with psoriasis. No patients with
      gastrointestinal (N = 6) or neurological disorders (N = 5) flared. Only 2 (4%)
      patients discontinued treatment due to flare, but 15 (29%) developed other irAEs
      and 4 (8%) discontinued treatment. In patients with prior ipilimumab irAEs
      requiring immunosuppression (N = 67) the response rate was 40%. Two (3%) patients
      had a recurrence of the same ipilimumab irAEs, but 23 (34%) developed new irAEs
      (14, 21% grade 3-4) and 8 (12%) discontinued treatment. There were no treatment
      related deaths. Conclusions: In melanoma patients with preexisting ADs or major
      irAEs with ipilimumab, anti-PD-1 induced relatively frequent immune toxicities,
      but these were often mild, easily managed and did not necessitate discontinuation
      of therapy, and a significant proportion of patients achieved clinical responses.
      The results support that anti-PD-1 can be administered safely and can achieve
      clinical benefit in patients with preexisting ADs or prior major irAEs with
      ipilimumab.

PMID- 27687306
TI  - Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma
      with fully annotated clinical follow-up.
AB  - Background: Lung adenocarcinomas (LUADs) lead to the majority of deaths
      attributable to lung cancer. We performed whole-exome sequencing (WES) and immune
      profiling analyses of a unique set of clinically annotated early-stage LUADs to
      better understand the pathogenesis of this disease and identify clinically
      relevant molecular markers. Methods: We performed WES of 108 paired stage I-III
      LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune
      markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B)
      were profiled by imaging-based immunohistochemistry (IHC) in a subset of LUADs (n
      = 92). Associations among mutations, immune markers and clinicopathological
      variables were analyzed using ANOVA and Fisher's exact test. Cox proportional
      hazards regression models were used for multivariate analysis of clinical
      outcome. Results: LUADs in this cohort exhibited an average of 243 coding
      mutations. We identified 28 genes with significant enrichment for mutation. SETD2
      mutated LUADs exhibited relatively poor recurrence- free survival (RFS) and
      mutations in STK11 and ATM were associated with poor RFS among KRAS-mutant
      tumors. EGFR, KEAP1 and PIK3CA mutations were predictive of poor response to
      adjuvant therapy. Immune marker analysis revealed that LUADs in smokers and with
      relatively high mutation burdens exhibited increased levels of immune markers.
      Analysis of immunophenotypes revealed that LUADs with STK11 mutations exhibited
      relatively low levels of infiltrating CD4+/CD8+ T-cells indicative of a muted
      immune response. Tumoral PD-L1 was significantly elevated in TP53 mutant LUADs
      whereas PIK3CA mutant LUADs exhibited markedly down-regulated PD-L1 expression.
      LUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and
      Granzyme B levels indicative of augmented natural killer (NK) cell infiltration.
      Conclusion(s): Our study highlights molecular and immune phenotypes that warrant
      further analysis for their roles in clinical outcomes and personalized immune
      based therapy of LUAD.

PMID- 27687307
TI  - Multicenter randomized phase II study of cisplatin and fluorouracil plus
      docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as
      preoperative chemotherapy for resectable esophageal squamous cell carcinoma
      (OGSG1003).
AB  - Background: This phase II trial evaluated the efficacy of cisplatin and
      fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of
      patients with resectable locally advanced esophageal squamous cell carcinoma
      (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus
      Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an
      alternative regimen in a new phase III trial investigating the optimal
      neoadjuvant treatment of patients with ESCC. Patients and methods: Patients with
      resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35
      mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous
      infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2
      i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3
      weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The
      primary end point was RFS, analyzed by the intention-to-treat. Results: Between
      October 2011 and October 2013, 162 patients at 10 institutions were enrolled in
      the study, all of whom were eligible and randomly assigned to the two groups (81
      to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and
      DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and
      overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio
      0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P =
      0.08), respectively. Conclusion: Compared with ACF, DCF chemotherapy was
      associated with prolonged RFS for patients with resectable advanced ESCC. Thus,
      DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable
      ESCC. Clinical Trial Registration: University Hospital Medical Information
      Network Clinical Trials Registry of Japan (identification number
      UMIN000004555/000004616).

PMID- 27687308
TI  - Impact of early palliative care on caregivers of patients with advanced cancer:
      cluster randomised trial.
AB  - Background: Early palliative care improves the quality of life (QoL) and
      satisfaction with care of patients with advanced cancer, but little is known
      about its effect on caregivers. Here, we report outcomes of caregiver
      satisfaction with care and QoL from a trial of early palliative care. Patients
      and methods: Twenty-four medical oncology clinics were cluster-randomised,
      stratified by tumour site (lung, gastrointestinal, genitourinary, breast and
      gynaecological), to early palliative care team referral, or to standard oncology
      care with palliative care only as needed. Caregivers of patients with advanced
      cancer (clinical prognosis of 6-24 months, Eastern Cooperative Oncology Group 0
      2) in both trial arms completed validated measures assessing satisfaction with
      care (FAMCARE-19) and QoL [SF-36v2 Health Survey; Caregiver QoL-Cancer (CQoL-C)],
      at baseline and monthly for 4 months. We used a multilevel linear random
      intercept mixed-effect model to test whether there was improvement in the
      intervention group relative to the control group over 3 and 4 months. Results: A
      total of 182 caregivers completed baseline measures (94 intervention, 88
      control); 151 caregivers (77 intervention, 74 control) completed at least one
      follow-up assessment. Satisfaction with care improved in the palliative
      intervention group compared with controls over 3 months (P = 0.007) and 4 months
      (P = 0.02). There was no significant improvement in the intervention group
      compared with controls for CQoL-C (3 months: P = 0.92, 4 months: P = 0.51),
      Physical Component Summary of the SF-36v2 Health Survey (3 months: P = 0.83, 4
      months: P = 0.20), or Mental Component Summary of the SF-36v2 Health Survey (3
      months: P = 0.87, 4 months: P = 0.60). Conclusion: Early palliative care
      increased satisfaction with care in caregivers of patients with advanced cancer.
      ClinicalTrials.gov identifier: NCT01248624.

PMID- 27687312
TI  - PARP inhibition in BRCA2-mutated prostate cancer.

PMID- 27687309
TI  - Quantitative proteomic analysis of HER2 expression in the selection of gastric
      cancer patients for trastuzumab treatment.
AB  - Background: A wide range of response rates have been reported in HER2-positive
      gastric cancer (GC) patients treated with trastuzumab. Other HER2-targeted
      therapies for GC have yet to show efficacy in clinical trials. These findings
      raise question about the ability of standard HER2 diagnostics to accurately
      distinguish between GC patients who would and would not benefit from anti-HER2
      therapies. Patients and methods: GC patients (n = 237), including a subset from
      the Trastuzumab in GC (ToGA) trial were divided into three groups based on HER2
      status and history of treatment with standard chemotherapy or chemotherapy plus
      trastuzumab. We applied mass spectrometry-based proteomic analysis to quantify
      HER2 protein expression in formalin-fixed tumor samples. Using HER2 expression as
      a continuous variable, we defined a predictive protein level cutoff to identify
      which patients would benefit from trastuzumab. We compared quantitated protein
      level with clinical outcome and HER2 status as determined by conventional HER2
      diagnostics. Results: Quantitative proteomics detected a 115-fold range of HER2
      protein expression among patients diagnosed as HER2 positive by standard methods.
      A protein level of 1825 amol/ug was predicted to determine benefit from the
      addition of trastuzumab to chemotherapy. Trastuzumab treated patients with HER2
      protein levels above this cutoff had twice the median overall survival (OS) of
      their counterparts below the cutoff (35.0 versus 17.5 months, P = 0.011).
      Conversely, trastuzumab-treated patients with HER2 levels below the cutoff had
      outcomes similar to HER2-positive patients treated with chemotherapy.
      (Progression-free survival = 7.0 versus 6.5 months: P = 0.504; OS = 17.5 versus
      12.6 months: P = 0.520). HER2 levels were not prognostic for response to
      chemotherapy. Conclusions: Proteomic analysis of HER2 expression demonstrated a
      quantitative cutoff that improves selection of GC patients for trastuzumab as
      compared with current diagnostic methods.

PMID- 27687313
TI  - Prevention of fluoropyrimidine toxicity: do we still have to try our patient's
      luck?

PMID- 27687311
TI  - Mutant KIT as imatinib-sensitive target in metastatic sinonasal carcinoma.
AB  - Background: Sinonasal carcinomas (SNCs) comprise various rare tumor types that
      are characterized by marked histologic diversity and largely unknown molecular
      profiles, yet share an overall poor prognosis owing to an aggressive clinical
      course and frequent late-stage diagnosis. The lack of effective systemic
      therapies for locally advanced or metastatic SNC poses a major challenge to
      therapeutic decision making for individual patients. We here aimed to identify
      actionable genetic alterations in a patient with metastatic SNC whose tumor,
      despite all diagnostic efforts, could not be assigned to any known SNC category
      and was refractory to multimodal therapy. Patients and methods: We used whole
      exome and transcriptome sequencing to identify a KIT exon 11 mutation
      (c.1733_1735del, p.D579del) as potentially druggable target in this patient and
      carried out cancer hotspot panel sequencing to detect secondary resistance
      conferring mutations in KIT. Furthermore, as a step towards clinical exploitation
      of the recently described signatures of mutational processes in cancer genomes,
      we established and applied a novel bioinformatics algorithm that enables
      supervised analysis of the mutational catalogs of individual tumors. Results:
      Molecularly guided treatment with imatinib in analogy to the management of
      gastrointestinal stromal tumor (GIST) resulted in a dramatic and durable response
      with remission of nearly all tumor manifestations, indicating a dominant driver
      function of mutant KIT in this tumor. KIT dependency was further validated by a
      secondary KIT exon 17 mutation (c.2459_2462delATTCinsG, p.D820_S821delinsG) that
      was detected upon tumor progression after 10 months of imatinib treatment and
      provided a rationale for salvage therapy with regorafenib, which has activity
      against KIT exon 11/17 mutant GIST. Conclusions: These observations highlight the
      potential of unbiased genomic profiling for uncovering the vulnerabilities of
      individual malignancies, particularly in rare and unclassifiable tumors, and
      underscore that KIT exon 11 mutations represent tractable therapeutic targets
      across different histologies.

PMID- 27687314
TI  - Antiarrhythmic drugs in out-of-hospital cardiac arrest: What counts and what
      doesn't?

PMID- 27687315
TI  - [Type II Quadratus Lumborum block for a sub-total gastrectomy in a septic
      patient].
AB  - INTRODUCTION AND OBJECTIVES: Quadratus Lumborum block was recently described and
      has already shown good results as an analgesic technique in abdominal surgeries,
      having the potential to significantly reduce opioids consumption and be a valid
      alternative to epidural catheter. We performed a type II Quadratus Lumborum block
      for analgesia in a septic patient having a sub-total gastrectomy. CASE REPORT: An
      80 year-old, ASA III, male patient, weighting 50kg, with a history of arterial
      hypertension and hypercholesterolemia, diagnosed with sepsis due to purulent
      peritonitis was submitted to an open laparotomy. Bilateral ultrasound-guided type
      II Quadratus Lumborum block was performed before surgery, using 10mL of
      levobupivacaine 0.25% and 5mL of mepivacaine 1%, per side. Pain relief was
      achieved 5minutes after injection and the patient referred no pain in the
      immediate postoperative period. DISCUSSION: Type II Quadratus Lumborum block may
      be considered a valid alternative for postoperative analgesia in a septic patient
      undergoing major abdominal surgery with some relative contraindications to
      epidural catheter placement. It allowed us to achieve excellent pain management
      avoiding opioids usage. However, more reports are still needed to properly access
      its usefulness.

PMID- 27687316
TI  - [Effect of equipotent doses of bupivacaine and ropivacaine in high-fat diet fed
      neonatal rodent model].
AB  - OBJECTIVES: The increase in the prevalence of obesity presents a significant
      health and economic problem. Obesity has been reported to be a major contributor
      to variety of chronic diseases. Childhood obesity has been rising over the past
      decades leading to various complications in health. Millions of infants and
      children undergo surgery every year on various health grounds. The present
      investigation was undertaken to evaluate the effect of spinal anesthesia of
      equipotent doses of ropivacaine and bupivacaine on over-weight neonatal rats.
      METHODS: The Sprague-Dawley rat pups were overfed on high fat diet to induce
      obesity. Behavioral assessments for sensory and motor blockade was made by
      evaluating thermal and mechanical withdrawal latencies at various time intervals
      following intrathecal injections of bupivacaine (5.0mg.kg-1) and ropivacaine
      (7.5mg.kg-1) in P14 rats. Spinal tissue was analyzed for apoptosis by
      determination of activated caspase-3 using monoclonal anti-activated caspase-3
      and Fluoro-Jade C staining. Long-term spinal function in P30 rat pups was
      evaluated. RESULTS: Exposure to intrathecal anesthesia in P14 increased thermal
      and mechanical latencies and was observed to increase apoptosis as presented by
      increase in activated caspase-3 and Fluro-Jade C positive cells. Significant
      alterations in spinal function were observed in high fat diet-fed pups as against
      non-obese control pups that were on standard diet. Bupivacaine produced more
      pronounced apoptotic effects on P14 pups; ropivacaine however produced long
      lasting effects as evidenced in motor function tests at P30. CONCLUSION:
      Ropivacaine and bupivacaine induced spinal toxicity that was more pronounced in
      over-fed rat pups as against normal controls.

PMID- 27687317
TI  - [Anesthesia in anti-N-methyl-d-aspartate receptor encephalitis - is general
      anesthesia a requisite? A case report].
AB  - Anti-N-methyl-d-aspartate receptor encephalitis is a recently described
      neurological disorder and an increasingly recognized cause of psychosis, movement
      disorders and autonomic dysfunction. We report 20-year-old Chinese female who
      presented with generalized tonic-clonic seizures, recent memory loss, visual
      hallucinations and abnormal behavior. Anti-N-methyl-d-aspartate receptor
      encephalitis was diagnosed and a computed tomography scan of abdomen reviewed a
      left adnexal tumor. We describe the first such case report of a patient with anti
      N-methyl-d-aspartate receptor encephalitis who was given a bilateral transversus
      abdominis plane block as the sole anesthetic for removal of ovarian tumor. We
      also discuss the anesthetic issues associated with anti-N-methyl-d-aspartate
      receptor encephalitis. As discovery of tumor and its removal is the focus of
      initial treatment in this group of patients, anesthetists will encounter more
      such cases in the near future.

PMID- 27687318
TI  - [Hypotension and bradycardia before spinal anesthesia].
AB  - I report a case of hypotension and bradycardia before spinal anesthesia in a
      pregnant woman with mild to moderate hypertension treated with nifedipine and
      methyldopa, scheduled for an elective cesarean delivery. She had the history of
      neurally-mediated syncopes. Two main factors (increased vagal tone and adverse
      effects of antihypertensive drugs) could explain the hypotension and bradycardia
      before spinal anesthesia. Monitoring allowed recognizing the problem and
      corrected it. Thus, it was avoided a disaster in anesthesia, as hemodynamic
      changes after spinal anesthesia, they would have joined to previous hypotension
      and bradycardia, which would have caused even a cardiac arrest.

PMID- 27687319
TI  - First-line treatment of NSCLC with bevacizumab: real world data from an Italian
      regional based survey.
AB  - BACKGROUND: We aimed to explore the use of platinum plus bevacizumab in a real
      world NSCLC population. PATIENTS AND METHODS: We retrospectively collected data
      from patients affected by NS-NSCLC treated with platinum plus bevacizumab across
      Tuscany. RESULTS: We evaluated 62 (median age: 63.5 [30-77] years) pts. All but
      one presented with adenocarcinoma and the majority had ECOG PS of 0/1. 17.7%
      presented with central lesion, 11.3% with brain metastasis, 38.7% with
      hypertension and 4.8% with mild haemoptysis. We observed a median time to
      progression (TTP) of 6.5 [2-37] and a median overall survival (OS) of 10.5 [2-39]
      months. Overall response rate (ORR) was 59.6% with a disease control rate (DCR)
      of 80.6%. Safety profile was acceptable. We observed five cardiovascular events
      and two major bleedings with no toxic deaths. CONCLUSION: Safety and efficacy
      real world data are consistent with those from clinical trials even in a less
      selected population.

PMID- 27687320
TI  - Study of the optimum haplotype length to build genomic relationship matrices.
AB  - BACKGROUND: As genomic data becomes more abundant, genomic prediction is more
      routinely used to estimate breeding values. In genomic prediction, the
      relationship matrix ([Formula: see text]), which is traditionally used in genetic
      evaluations is replaced by the genomic relationship matrix ([Formula: see text]).
      This paper considers alternative ways of building relationship matrices either
      using single markers or haplotypes of different lengths. We compared the
      prediction accuracies and log-likelihoods when using these alternative
      relationship matrices and the traditional [Formula: see text] matrix, for real
      and simulated data. METHODS: For real data, we built relationship matrices using
      50k genotype data for a population of Brahman cattle to analyze three traits:
      scrotal circumference (SC), age at puberty (AGECL) and weight at first corpus
      luteum (WTCL). Haplotypes were phased with hsphase and imputed with BEAGLE. The
      relationship matrices were built using three methods based on haplotypes of
      different lengths. The log-likelihood was considered to define the optimum
      haplotype lengths for each trait and each haplotype-based relationship matrix.
      RESULTS: Based on simulated data, we showed that the inverse of [Formula: see
      text] matrix and the inverse of the haplotype relationship matrices for methods
      using one-single nucleotide polymorphism (SNP) phased haplotypes provided
      coefficients of determination (R2) close to 1, although the estimated genetic
      variances differed across methods. Using real data and multiple SNPs in the
      haplotype segments to build the relationship matrices provided better results
      than the [Formula: see text] matrix based on one-SNP haplotypes. However, the
      optimal haplotype length to achieve the highest log-likelihood depended on the
      method used and the trait. The optimal haplotype length (7 to 8 SNPs) was similar
      for SC and AGECL. One of the haplotype-based methods achieved the largest
      increase in log-likelihood for SC, i.e. from -1330 when using [Formula: see text]
      to -1325 when using haplotypes with eight SNPs. CONCLUSIONS: Building the
      relationship matrix by using haplotypes that comprise multiple SNPs will increase
      the accuracy of estimated breeding values. However, the optimum haplotype length
      that shows the correct relationship among individuals for each trait can be
      derived from the data.

PMID- 27687321
TI  - Predictors of renal dysfunction after endovascular and open repair of abdominal
      aortic aneurysms.
AB  - OBJECTIVE: Renal complications after repair of abdominal aortic aneurysms (AAAs)
      have been associated with increased morbidity and mortality. However, limited
      data have assessed risk factors for renal complications in the endovascular era.
      This study aimed to identify predictors of renal complications after endovascular
      AAA repair (EVAR) and open repair. METHODS: Patients who underwent EVAR or open
      repair of a nonruptured infrarenal AAA between 2011 and 2013 were identified in
      the National Surgical Quality Improvement Project Targeted Vascular module.
      Patients on hemodialysis preoperatively were excluded. Renal complications were
      defined as new postoperative dialysis or creatinine increase >2 mg/dL. Patient
      demographics, comorbidities, glomerular filtration rate (GFR), operative details,
      and outcomes were compared using univariate analysis between those with and
      without renal complications. Multivariable logistic regression was used to
      identify independent predictors of renal complications. RESULTS: We identified
      4503 patients who underwent elective repair of an infrarenal AAA (EVAR: 3869,
      open repair: 634). Renal complication occurred in 1% of patients after EVAR and
      in 5% of patients after open repair. There were no differences in comorbidities
      between patients with and without renal complications. A preoperative GFR <60
      mL/min/1.73m2 occurred more frequently among patients with renal complications
      (EVAR: 81% vs 37%, P < .01; open: 60% vs 34%, P < .01). The 30-day mortality was
      also significantly increased (EVAR: 55% vs 1%, P < .01; open: 30% vs 4%, P <
      .01). After adjustment, renal complications were strongly associated with 30-day
      mortality (odds ratio [OR], 38.3; 95% confidence interval [CI], 20.4-71.9).
      Independent predictors of renal complications included GFR <60 mL/min/1.73m2 (OR,
      4.6; 95% CI, 2.4-8.7), open repair (OR, 2.6; 95% CI, 1.3-5.3), transfusion (OR,
      6.1; 95% CI, 3.0-12.6), and prolonged operative time (OR, 3.0; 95% CI, 1.6-5.6).
      CONCLUSIONS: Predictors of renal complications include elevated baseline GFR,
      open approach, transfusion, and prolonged operative time. Given the dramatic
      increase in mortality associated with renal complications, care should be taken
      to use renal protective strategies, achieve meticulous hemostasis to limit
      transfusions, and to use an endovascular approach when technically feasible.

PMID- 27687322
TI  - Early infection risk with primary versus staged Hemodialysis Reliable Outflow
      (HeRO) graft implantation.
AB  - OBJECTIVE: This study evaluated whether the use of a staged Hemodialysis Reliable
      Outflow (HeRO; Merit Medical, South Jordan, Utah) implantation strategy incurs
      increased early infection risk compared with conventional primary HeRO
      implantation. METHODS: A retrospective review was performed of 192 hemodialysis
      patients who underwent HeRO graft implantation: 105 patients underwent primary
      HeRO implantation in the operating room, and 87 underwent a staged implantation
      where a previously inserted tunneled central venous catheter was used for
      guidewire access for the venous outflow component. Within the staged implantation
      group, 32 were performed via an existing tunneled hemodialysis catheter
      (incidentally staged), and 55 were performed via a tunneled catheter inserted
      across a central venous occlusion in an interventional radiology suite
      specifically for HeRO implantation (intentionally staged). Early infection was
      defined as episodes of bacteremia or HeRO infection requiring resection <=30 days
      of HeRO implantation. RESULTS: For staged HeRO implantations, the median interval
      between tunneled catheter insertion and conversion to a HeRO graft was 42 days.
      The overall HeRO-related infection rate <=30 days of implantation was 8.6% for
      primary HeRO implantation and 2.3% for staged implantations (P = .12). The rates
      of early bacteremia and HeRO resection requiring surgical resection were not
      significantly different between groups (P = .19 and P = .065, respectively), nor
      were age, gender, laterality, anastomosis to an existing arteriovenous access,
      human immunodeficiency virus status, diabetes, steroids, chemotherapy, body mass
      index, or graft location. None of the patient variables, techniques, or graft
      related variables correlated significantly with the early infection rate.
      CONCLUSIONS: The staged HeRO implantation strategy did not result in an increased
      early infection risk compared with conventional primary implantation and is thus
      a reasonable strategy for HeRO insertion in hemodialysis patients with complex
      central venous disease.

PMID- 27687323
TI  - Midterm results from a physician-sponsored investigational device exemption
      clinical trial evaluating physician-modified endovascular grafts for the
      treatment of juxtarenal aortic aneurysms.
AB  - OBJECTIVE: The objective of this study was to report midterm results of an
      ongoing physician-sponsored investigational device exemption pivotal clinical
      trial using physician-modified endovascular grafts (PMEGs) for treatment of
      patients with juxtarenal aortic aneurysms who are deemed unfit for open repair.
      METHODS: Data from a nonrandomized, prospective, consecutively enrolling
      investigational device exemption clinical trial were used. Data collection began
      on April 1, 2011, and data lock occurred on May 31, 2015, with outcomes analysis
      through December 31, 2015. Primary safety and efficacy end points were used to
      measure treatment success. The primary safety end point was defined as the
      proportion of subjects who experienced a major adverse event within 30 days of
      the procedure. The primary efficacy end point was the proportion of subjects who
      achieved treatment success. Treatment success required the following at 12
      months: technical success, defined as successful delivery and deployment of a
      PMEG with preservation of those branch vessels intended to be preserved; and
      freedom from type I and III endoleak, stent graft migration >10 mm, aortic
      aneurysm sack enlargement >5 mm, and aortic aneurysm rupture or open conversion.
      RESULTS: During the 50-month study period, 64 patients were enrolled; 60 began
      the implant procedure and 59 received the PMEG implant. Aneurysm anatomy,
      operative details, and lengths of stay were recorded and included aneurysm
      diameter (mean, 65.9 mm; range, 49-104 mm), proximal seal zone length (mean, 40.8
      mm; range, 18.9-72.2 mm), graft manufacture time (mean, 55.1 minutes), procedure
      time (mean, 156.8 minutes), fluoroscopy time (mean, 39.6 minutes), contrast
      material use (mean, 75.3 mL), estimated blood loss (mean, 213 mL), and length of
      hospital stay (mean, 4.1 days) with intensive care unit length of stay (mean, 2.2
      days). There were 145 fenestrations made for 110 renal arteries and 38 superior
      mesenteric arteries (SMAs). One patient had an SMA stent placed before the
      procedure for severe stenosis, and one subject had the SMA stented during the
      procedure. Renal arteries were stented whenever possible (93%). There were 102
      stented renal arteries in 58 patients. There were no open conversions or
      explantations. Thirty-day mortality was 5.1% (3/59). There were zero type Ia, one
      type Ib, and two type III endoleaks during follow-up treated with successful
      reintervention. The overall rate of major adverse events at 30 days was 11.9%.
      The primary efficacy end points were achieved in 94.1% of patients. CONCLUSIONS:
      These midterm results are favorable and verify our early report that endovascular
      repair with PMEG is safe and effective for managing patients with juxtarenal
      aortic aneurysms. PMEG has exceptional midterm rates of morbidity, mortality, and
      endoleak and may outperform standard endovascular aneurysm repair with favorable
      anatomy. In patients who are poor open surgical candidates who present with
      symptomatic or ruptured juxtarenal aortic aneurysms, PMEG continues to be an
      extremely appealing option as reliable off-the-shelf solutions are not widely
      available. Preoperative planning remains the key ingredient for success with use
      of these techniques.

PMID- 27687324
TI  - Revascularization of smokers with claudication is not predicted to limit quality
      of life despite a higher risk of late failure.
AB  - OBJECTIVE: Tobacco smoking after lower extremity revascularization for
      claudication has repeatedly been shown to increase the risk of adverse events,
      such that many vascular specialists consider that refusal to abstain from smoking
      constitutes a major contraindication to open surgical bypass or endovascular
      intervention. METHODS: A Markov decision analysis (DA) model was used to compare
      the options of direct revascularization vs medical therapy only in smokers with
      claudication. The primary outcome was calculated quality of life (cQoL),
      determined for each patient at follow-up based on the outcomes of the treatment
      received. Markov DA software was used to predict the QoL for each treatment
      option preoperatively based on smoking status. RESULTS: Among patients referred
      during a recent 64-month period with vasculogenic claudication, 94 were actively
      smoking compared with 217 who were not. The DA model predicted that if the
      patients who smoked were to discontinue smoking, the best therapy would be bypass
      surgery for 77% and endovascular intervention for 17%. However, despite at least
      doubling the risks with intervention in the patients who continue to smoke, the
      DA model still predicted that 78% and 9% would fare better with open surgical or
      endovascular intervention, respectively. Among actively smoking patients, open
      surgical (3%) or endovascular (4%) therapies were initially performed in few
      patients, whereas 93% were offered only medical therapy. Among initial
      nonsmokers, revascularization was performed by open (27%) or endovascular (42%)
      means. At 3 years, the median (interquartile range [IQR]) cQoL was lower in
      initial smokers than in nonsmokers (0.73 [IQR, 0.73-0.77] vs 0.82 [IQR, 0.75
      0.86]; P < .0001), primarily because of a lack of revascularization for smokers.
      Among initial smokers who did undergo revascularization initially, because of
      progression of symptoms, or after smoking cessation, cQoL was similar to initial
      nonsmokers (0.77 [IQR, 0.73-0.84] vs 0.73 [IQR, 0.73-0.73]; P = .37). Although
      26% of initial smokers had stopped by the time of their last follow-up, 10% of
      initially nonsmoking patients were smoking at follow-up. However, among all
      patients undergoing intervention, the cQoL of patients smoking at the time of
      last their follow-up was similar to nonsmokers (0.82 [IQR, 0.82-0.86] vs 0.83
      [IQR, 0.73-0.86]; P = .99). CONCLUSIONS: Patients with claudication who smoke may
      be denied the symptom improvement associated with revascularization, yet
      recidivism for smoking also occurs among patients who have stopped smoking in
      order to receive revascularization. The strategy not to directly revascularize
      patients with claudication who continue to smoke does not appear to maximize
      patient midterm QoL.

PMID- 27687325
TI  - Limb-sparing surgery with vascular reconstruction for malignant lower extremity
      soft tissue sarcoma.
AB  - BACKGROUND: The standard of care for lower extremity soft tissue sarcoma (STS) is
      limb-sparing surgery. A small subset of these patients will require concomitant
      vascular reconstruction to ensure adequate resection and to preserve limb
      viability and function. The aim of this study was to evaluate outcomes in these
      patients with respect to wound healing and postoperative functional status.
      METHODS: Outcomes for a total of 154 patients treated for malignant lower
      extremity STS during an 8-year period between 2005 and 2013 were entered in a
      prospective registry. Treatment was by medical management in 3 patients (2%),
      limb-sparing surgery with vascular reconstruction (LSVR) in 9 patients (6%), and
      limb-sparing surgery without vascular reconstruction (LS) in 142 patients (92%).
      The registry and patient records and the intraoperative records were consulted to
      determine the primary outcomes of patient survival and time for complete wound
      healing. The functional status of patients was assessed using the Musculoskeletal
      Tumor Society (MSTS) functional assessment score before surgery and at 6 and 12
      months after surgery. RESULTS: Mean follow-up time was 74.7 months for the LSVR
      group and 53.4 months for the LS group. The mean time to complete wound healing
      was significantly longer in LSVR vs LS patients (88 days vs 34 days,
      respectively; P = .002), and overall survival was lower in LSVR patients (P =
      .01). Seven of the 9 LSVR patients required a total of 12 additional procedures
      to achieve wound healing, including 9 procedures to drain seromas (incision and
      drainage) with vacuum-assisted closure in 4 cases. Plastic surgery intervention
      was required in three patients, including one skin graft, one gracilis pedicle
      flap, and one vertical rectus abdominis myocutaneous flap. There was no
      significant difference in the mean MSTS scores preoperatively, at 6 months, and
      at 1 year after surgery between the two groups (27, 25, and 29 for LSVR vs 28,
      31, and 31 for LS, respectively; P = .63, .11, and .67, respectively).
      CONCLUSIONS: The need for vascular reconstruction during limb-sparing surgery for
      lower extremity malignant STS is rare in a high-volume sarcoma center. Overall
      survival was lower in these patients, and the time to complete wound healing is
      prolonged and requires multiple secondary interventions. However, postoperative
      functional status as assessed by the MSTS is acceptable and comparable to that of
      patients not requiring vascular reconstruction.

PMID- 27687326
TI  - Arterial complications of vascular Ehlers-Danlos syndrome.
AB  - BACKGROUND: Vascular Ehlers-Danlos syndrome (EDS) is a relatively rare genetic
      syndrome that occurs owing to disorders in the metabolism of fibrillary collagen.
      These defects affect the soft connective tissues resulting in abnormalities in
      the skin, joints, hollow organs, and blood vessels. Patients with these defects
      frequently present at a young age with spontaneous arterial complications
      involving the medium-sized arteries. Complications involving the hollow organs,
      such as spontaneous colonic perforation, are observed as well. Given the
      fragility of the soft tissue, open and endovascular intervention on patients with
      vascular EDS is fraught with high complication rates. METHODS: A PubMed search
      was performed to identify manuscripts published related to vascular EDS. This
      search included more than 747 articles. These findings were cross-referenced
      using key terms, including endovascular, embolization, surgery, genetics,
      pathophysiology, connective tissue disorders, vascular complications, systematic
      review, type III collagen, and COL3A1. RESULTS: The references in key articles
      and review articles were evaluated for additional resources not identified in the
      PubMed search. Care must be taken to balance the risk of intervention vs the risk
      of continued observation. Life-threatening hemorrhage, however, mandates
      intervention. CONCLUSIONS: With careful, altered approaches to tissue handling,
      endovascular approaches may provide a safer option for managing the arterial
      complications observed in patients with vascular EDS. Additional hope may also be
      found in the use of pharmacologic agents that reduce the incidence and severity
      of the arterial complications.

PMID- 27687328
TI  - Reconstruction for renal artery aneurysms using the tailoring technique.
AB  - OBJECTIVE: Renal artery (RA) aneurysm (RAA) is a rare and complex disease.
      Treatment options for a RAA include endovascular surgery and open surgery with ex
      vivo repair or in situ reconstruction. This study evaluated the long-term outcome
      after vascular reconstruction of RAAs using the tailoring technique. Tailoring or
      aneurysmorrhaphy means a partial resection of the aneurysm with direct suture of
      the remaining arterial wall. METHODS: A single-center retrospective study was
      conducted between January 1990 and December 2015. The tailoring technique was
      used to surgically repair 88 RAAs in 80 patients (52 women) with a mean age of
      52.9 years. Patients' demographic data, vascular therapy, and renal function
      during follow-up were retrospectively evaluated. RESULTS: The localization of the
      RAA was at the right kidney in 58 patients. The mean size of the aneurysm was
      21.4 +/- 9.7 mm (range, 8-67 mm). Hypertension was diagnosed in 56 patients, and
      23 were asymptomatic. One RAA was ruptured. The overall morbidity rate was 16.3%,
      including bleeding (n = 4), RA stenosis (n = 3), RA occlusion (n = 4), RA
      dissection (n = 1), and myocardial infarction (n = 1). One patient died of
      myocardial infarction for a 30-day mortality rate of 1.3%. The 30-day primary
      patency rate was 90.0%. The 30-day secondary patency rate was 95.0%. Follow-up
      data were obtained from 71 patients who underwent tailoring in 78 RAAs. The mean
      follow-up period was 60.7 months (range 2-229 months). In 76.4% of patients with
      RAA and hypertension, RAA reconstruction contributed to the cure or improvement
      of hypertension. The long-term patency after RAA reconstruction was demonstrated
      in a Kaplan-Meier curve, with cumulative patency rates of 98.7%, 97.4%, 94.8%,
      and 92.3% after 18, 24, 36, and 48 months, respectively. Estimated survival rates
      were 98.8%, 97.5%, and 96.3% after 12, 48, and 60 months, with an estimated mean
      time of 216.5 +/- 7.2 months. CONCLUSIONS: The tailoring technique is a safe and
      effective procedure with good long-term outcomes. RAA reconstruction contributed
      to the cure or improvement of renovascular hypertension.

PMID- 27687329
TI  - Comparison among dimensionality reduction techniques based on Random Projection
      for cancer classification.
AB  - Random Projection (RP) technique has been widely applied in many scenarios
      because it can reduce high-dimensional features into low-dimensional space within
      short time and meet the need of real-time analysis of massive data. There is an
      urgent need of dimensionality reduction with fast increase of big genomics data.
      However, the performance of RP is usually lower. We attempt to improve
      classification accuracy of RP through combining other reduction dimension methods
      such as Principle Component Analysis (PCA), Linear Discriminant Analysis (LDA),
      and Feature Selection (FS). We compared classification accuracy and running time
      of different combination methods on three microarray datasets and a simulation
      dataset. Experimental results show a remarkable improvement of 14.77% in
      classification accuracy of FS followed by RP compared to RP on BC-TCGA dataset.
      LDA followed by RP also helps RP to yield a more discriminative subspace with an
      increase of 13.65% on classification accuracy on the same dataset. FS followed by
      RP outperforms other combination methods in classification accuracy on most of
      the datasets.

PMID- 27687327
TI  - Fast-degrading bioresorbable arterial vascular graft with high cellular
      infiltration inhibits calcification of the graft.
AB  - OBJECTIVE: Bioresorbable vascular grafts are biologically active grafts that are
      entirely reconstituted by host-derived cells through an inflammation-mediated
      degradation process. Calcification is a detrimental condition that can severely
      affect graft performance. Therefore, prevention of calcification is of great
      importance to the success of bioresorbable arterial vascular grafts. The
      objective of this study was to test whether fast-degrading (FD) bioresorbable
      arterial grafts with high cellular infiltration will inhibit calcification of
      grafts. METHODS: We created two versions of bioresorbable arterial vascular
      grafts, slow-degrading (SD) grafts and FD grafts. Both grafts had the same inner
      layer composed of a 50:50 poly(l-lactic-co-epsilon-caprolactone) copolymer
      scaffold. However, the outer layer of SD grafts was composed of poly(l-lactic
      acid) nanofiber, whereas the outer layer of FD grafts was composed of a
      combination of poly(l-lactic acid) and polyglycolic acid nanofiber. Both grafts
      were implanted in 8- to 10-week-old female mice (n = 15 in the SD group, n = 10
      in the FD group) as infrarenal aortic interposition conduits. Animals were
      observed for 8 weeks. RESULTS: von Kossa staining showed calcification in 7 of 12
      grafts in the SD group but zero in the FD group (P < .01, chi2 test). The cell
      number in the outer layer of FD grafts was significantly higher than in the SD
      grafts (SD, 0.87 +/- 0.65 * 103/mm2; FD, 2.65 +/- 1.91 * 103/mm2; P = .02).
      CONCLUSIONS: The FD bioresorbable arterial vascular graft with high cellular
      infiltration into the scaffold inhibited calcification of grafts.

PMID- 27687330
TI  - Delayed Obstruction With Asymptomatic Loss of Renal Function After
      Dextranomer/Hyaluronic Acid Copolymer (Deflux) Injection for Vesicoureteral
      Reflux: A Close Look at a Disturbing Outcome.
AB  - Dextranomer/hyaluronic acid copolymer (Deflux) first received Food and Drug
      Administration approval in 2001 for endoscopic injection in children with grade
      II-IV vesicoureteral reflux VUR. As experience has grown, Deflux has been used
      more liberally with encouraging results. We report 3 cases where Deflux was used
      in off-label fashion, resulting in delayed ureteral obstruction and loss of renal
      function (range 18-52 months postoperatively). We now place increased emphasis on
      the need for long-term follow-up after Deflux in both routine and complex cases,
      particularly in situations of off-label use.

PMID- 27687331
TI  - The association between the gut microbiota and the inflammatory bowel disease
      activity: a systematic review and meta-analysis.
AB  - BACKGROUND: The pathogenesis of inflammatory bowel diseases (IBD) involves
      complex interactions between the microbiome and the immune system. We evaluated
      the association between the gut microbiota and disease activity in IBD patients.
      METHODS: Systematic review of clinical studies based on a published protocol.
      Included patients had ulcerative colitis (UC) or Crohn's disease (CD) classified
      as active or in remission. We selected bacteria assessed in at least three
      studies identified through electronic and manual searches (November 2015). Bias
      control was evaluated with the Newcastle Ottawa scale (NOS). Results of random
      effects meta-analyses were presented as mean differences (MD). RESULTS: Three
      prospective and seven cross-sectional studies (NOS score 6-8) were included. Five
      studies included patients with CD (231 patients) and eight included patients with
      UC (392 patients). Compared to patients in remission, patients with active IBD
      had lower abundance of Clostridium coccoides (MD = -0.49, 95% CI: -0.79 to 
      0.19), Clostridium leptum (MD = -0.44, 95% CI: -0.74 to -0.14), Faecalibacterium
      prausnitzii (MD = -0.81, 95% CI: -1.23 to -0.39) and Bifidobacterium (MD = -0.37,
      95% CI: -0.56 to -0.17). Subgroup analyses showed a difference in all four
      bacteria between patients with UC classified as active or in remission. Patients
      with active CD had fewer C. leptum, F. prausnitzii and Bifidobacterium, but not
      C. coccoides. CONCLUSION: This systematic review suggests that dysbiosis may be
      involved in the activity of IBD and that there may be differences between
      patients with CD and UC.

PMID- 27687332
TI  - Complicated function of dopamine in Abeta-related neurotoxicity: Dual
      interactions with Tyr10 and SNK(26-28) of Abeta.
AB  - With the capability to inhibit the formation of amyloid beta peptides (Abeta)
      fibril, dopamine (DA) and other catechol derivatives have been considered for the
      potential treatment of Alzheimer's disease (AD). Such treatment, however, remains
      debatable because of the diverse functions of Abeta and DA in AD pathology.
      Moreover, the complicated oxidation accompanying DA has caused the majority of
      the previous research to focus on the binding of DA oxides onto Abeta. The
      molecular mechanism by which Abeta interacts with the reduction state of DA,
      which is correlative with the brain function, should be urgently explored. By
      controlling rigorous anaerobic experimental conditions, this work investigated
      the molecular mechanism of the Abeta/DA interaction, and two binding sites were
      revealed. For the binding of DA, Tyrosine (Tyr10) was identified as the strong
      binding site, and serine-asparagine-lysing (SNK(26-28)) segment was the weak
      binding segment. Furthermore, the Thioflavin T (THT) fluorescence confirmed DA's
      positive function of inhibiting Abeta aggregation through its weakly binding with
      SNK(26-28) segment. Meanwhile, 7-OHCCA fluorescence exhibited DA's negative
      function of enhancing OH generation through inhibiting the Abeta/Cu2+
      coordination. The viability tests of the neuroblastoma SH-SY5Y cells displayed
      that the coexistence of DA, Cu2+, and Abeta induced lower cell viability than
      free Cu2+, indicating the significant negative effect of excessive DA on AD
      progression. This research revealed the potential DA-induced damage in AD brain,
      which is significant for understanding the function of DA in AD neuropathology
      and for designing a DA-related therapeutic strategy for AD.

PMID- 27687333
TI  - Organometallic myoglobins: Formation of Fe-carbon bonds and distal pocket effects
      on aryl ligand conformations.
AB  - Bioorganometallic Fe-C bonds are biologically relevant species that may result
      from the metabolism of natural or synthetic hydrazines. The molecular structures
      of four new sperm whale mutant myoglobin derivatives with Fe-aryl moieties,
      namely H64A-tolyl-m, H64A-chlorophenyl-p, H64Q-tolyl-m, and H64Q-chlorophenyl-p,
      have been determined at 1.7-1.9A resolution. The structures reveal conformational
      preferences for the substituted aryls resulting from attachment of the aryl
      ligands to Fe at the site of net -NHNH2 release from the precursor hydrazines,
      and show distal pocket changes that readily accommodate these bulky ligands.

PMID- 27687334
TI  - Heat Wave: A Trigger of Electrical Storm in a Patient With Brugada Syndrome.

PMID- 27687336
TI  - Mandibular hypoplasia and narrow airway in goldenhar syndrome: Anticipation of
      difficult intubation with cone-beam computed tomography.

PMID- 27687335
TI  - New Oral Hypoglycemic Agents and Cardiovascular Risk. Crossing the Metabolic
      Border.
AB  - Sodium-glucose cotransporter 2 inhibitors are a novel pharmacological class of
      oral hypoglycemic agents that lower glucose levels by increasing renal glucose
      excretion in an insulin-independent manner. However, this seemingly simple
      mechanism has more complex indirect metabolic effects. The results of randomized
      clinical trials have shown that these inhibitors effectively lower blood glucose
      and glycated hemoglobin levels without increasing the risk of hypoglycemia and,
      at the same time, also reduce bodyweight and systolic blood pressure. In this
      review, we describe the mechanism of action, efficacy, and safety of currently
      marketed drugs, as well as other risk factors besides glucose that can
      potentially be modulated positively. Recent data on empagliflozin showing a
      significant cardiovascular benefit have compelled us to update knowledge of this
      new therapeutic class for the treatment of type 2 diabetes.

PMID- 27687337
TI  - Postanesthesia emergence in patients with post-traumatic stress disorder.
AB  - STUDY OBJECTIVE: Recovery from anesthesia may be complicated with development of
      severe panic symptoms and anxiety. Preexisting anxiety disorder has been reported
      as a risk factor for development of these symptoms. We aimed to examine the
      frequency of emergence delirium (EDL) among veterans diagnosed with posttraumatic
      stress disorders (PTSDs). DESIGN: Retrospective cohort. SETTING: Postoperative
      recovery area. PATIENTS: Perioperative information of 1763 consecutive patients
      who underwent a surgical procedure requiring general anesthesia were collected.
      The patients were grouped on the basis of previous diagnosis of PTSD. A total of
      317 patients were identified with a positive history of PTSD and were compared to
      1446 patients without such a history for the occurrence of EDL in the
      postanesthesia care unit (PACU) as the primary endpoint. MEASUREMENTS: Duration
      of stay in PACU in minutes and the frequency of hospital admission were the
      secondary endpoints. Multivariate binary logistic regression analysis was
      performed to identify the predictors of EDL among the veteran population. MAIN
      RESULTS: Emergence delirium was reported in 37 cases (2.1%) after general
      anesthesia. Fifteen (4.7%) of 317 patients with PTSD and 22 (1.5%) of 1446
      patients without history of PTSD demonstrated symptoms related to EDL in the PACU
      (P=.002). After propensity matching, there were 8 patients with EDL in the PTSD
      group whereas there were only 2 patients with EDL among controls. Posttraumatic
      stress disorder was also an independent predictor of EDL in multivariate analysis
      with an odds ratio of 6.66 and a 95% confidence interval of 2.04 to 21.72
      (P=.002). CONCLUSIONS: Posttraumatic stress disorder independently predicted the
      frequency of EDL even after correcting for preexisting depression and anxiety
      disorders. A relatively longer duration of PACU stay in PTSD patients may reflect
      raised awareness of the health care workers about this debilitating mental
      disorder.

PMID- 27687338
TI  - Cardiovascular magnetic resonance is successfully feasible in many patients aged
      3 to 8years without general anesthesia or sedation.
AB  - OBJECTIVES: Patients younger than 8 years are usually examined by cardiovascular
      magnetic resonance (CMR) under general anesthesia (GA) or sedation without
      intubation. Therefore, we sought to study the feasibility of CMR in patients aged
      3 to 8years without GA or sedation. PATIENTS: Data sets of 71 consecutive
      patients aged 3 to 8years were studied retrospectively. DESIGN: The total cohort
      was divided into 2 groups: a no-GA or sedation without intubation group (no-GA or
      sedation) and a GA or sedation without intubation group (GA or sedation).
      MEASUREMENTS: The patients' age, scan durations for each group, successfully
      answered clinical question, and number of sequences per study were compared
      between both groups. MAIN RESULTS: Scan duration in the no-GA or sedation group
      (n=44) was 35+/- 20minutes, and that in the GA or sedation group (n=27) was 60+/-
      31minutes (P<.001). The percentage of successful reports was 95% (42/44) in the
      no-GA or sedation group and 89% (24 of 27) in the GA or sedation group (P=.29).
      CONCLUSION: CMR in patients aged 3 to 8years is usually successfully feasible
      without GA or sedation.

PMID- 27687339
TI  - Acute stroke after total joint arthroplasty: a population-based trend analysis.
AB  - STUDY OBJECTIVES: This study aims to determine trends and predictors of acute
      stroke among total joint arthroplasty (TJA) patients using nationally
      representative data. DESIGN: Retrospective database review. SETTING: Nationwide
      Inpatient Sample database. PATIENTS: A total of 1,762,496 TJAs from 2002 to 2011.
      INTERVENTIONS: Patients underwent primary or revision total hip or total knee
      arthroplasty. MEASUREMENTS: Development of perioperative acute stroke. MAIN
      RESULTS: Among 1,762,496 TJAs, 2414 patients (0.14%) developed stroke; 1918
      (79.45%) cases were ischemic and the remaining 496 (20.55%) cases were
      hemorrhagic stroke. The incidence of stroke decreased steadily from 0.17% in 2002
      to 0.14% in 2011, which was statistically significant (P<.0001). The in-hospital
      mortality rate was much higher after stroke at 9% vs 0.15% for general TJA
      patients. Logistic regression analysis showed that stroke is a strong predictor
      of in-hospital mortality (odds ratio [OR], 27.73; 95% confidence interval [CI],
      23.06-33.05; P<.001). Independent predictors of stroke were presence of pulmonary
      circulation disorders (including pulmonary embolism; OR, 2.23; 95% CI, 1.73
      2.87), advanced diabetes mellitus (OR, 2.10; 95% CI, 1.61-2.73), cardiac
      arrhythmia (OR, 2.05; 95% CI, 1.83-2.29), peripheral vascular disease (OR, 1.74;
      95% CI, 1.42-2.12), valvular heart disease (OR, 1.67; 95% CI, 1.43-1.95), renal
      disease (OR, 1.66; 95% CI, 1.38-1.99), and revision hip (OR, 1.39; 95% CI, 1.18
      1.65). History of stroke or ischemic heart disease was not an independent
      predictor of stroke. CONCLUSIONS: Despite a decline in the rate of stroke and
      stroke-related mortality after TJA, stroke still seems to be a major cause of in
      hospital mortality. The present study outlines some risk factors for stroke after
      TJA. Recognition of these factors and identification of the at-risk patients may
      allow for appropriate allocation of resources and ability to minimize this
      complication after TJA.

PMID- 27687340
TI  - Anesthetic management of a myotonic dystrophy patient with paraganglionoma.
AB  - Myotonic dystrophy (DM), though rare, can significantly complicate anesthesia due
      to muscular and extra-muscular involvement. When this condition is compounded by
      a pheochromocytoma, anesthetizing such patients becomes extra challenging. We
      present a case report of a 61-year-old lady with congenital DM, with the whole
      gamut of associated features, was diagnosed with a noradrenaline secreting
      paraganglionoma following investigation of refractory hypertension. We
      anesthetized her for an open resection of the lesion. The conduct of anesthesia
      and recovery of this patient is described. Our experience suggests that
      anesthetizing these patients though challenging can be safely managed with
      relaxant general anesthesia and epidural analgesia with meticulous care pre,
      intra and post-surgical intervention. 

PMID- 27687341
TI  - Oral dexmedetomidine for preoperative sedation in an adult uncooperative autistic
      patient.
AB  - We describe preoperative sedation with oral dexmedetomidine 5 mcg/kg in an
      uncooperative adult with autism and developmental delay. The sedation with oral
      dexmedetomidine achieved good sedation level (Ramsey 4-5), allowing for calm
      transfer of the patient to the operating room and uneventful induction of
      anesthesia. 

PMID- 27687342
TI  - Multisource feedback in professionalism for anesthesia residents.
AB  - STUDY OBJECTIVE: To assess professionalism in anesthesiology residents, it is
      important to obtain evaluations from people with whom they interact on daily
      basis. The purpose of this study was to evaluate the effect of a Multisource
      feedback (MSF) on resident's professional behavior and to assess the effect of
      faculty feedback on resident performance. DESIGN: This study was a two-group
      randomized clinical trial. SETTING: Residents were recruited from Cleveland
      Clinic Children's Hospital. PATIENTS: Participants included twenty eight
      residents doing a two-month rotation in Pediatric Anesthesia. INTERVENTIONS:
      Multisource feedback questionnaires were developed and then validated using face
      and content validity. Residents were randomly assigned to a feedback group or a
      control group. Both groups received the MSF evaluation. Only the group assigned
      to feedback had a 'coaching meeting' every month creating strategies for
      improvement. MEASUREMENTS: MSF questionnaires were validated using a face
      validation and expert content validity. The effect of MSF on a professionalism
      questionnaire was assessed using analysis of covariance and linear mixed effects
      regression models. MAIN RESULTS: Observed test-retest agreement was greater than
      0.90 for all items, with more than half of kappa statistics greater than 0.50.
      Cronbach's alpha was 0.71.The MSF increased the self-assessment score with an
      estimated effect of 0.21 (95% CI 0.06, 0.37), P=.015. There was no detected
      effect on patient family evaluation, with mean difference (CI) in change from
      baseline of 0.03 (-0.15, 0.21), P=.77, faculty evaluation, 0.21 (-0.02, 0.44),
      P=.08, or coworker evaluation 0.13 (-0.11, 0.37). CONCLUSIONS: Our new multi
      source feedback questionnaire to assess professionalism had good reliability and
      internal consistency. Using our validated questionnaire we assessed the effect of
      a monthly feedback to improve professionalism in anesthesia residents. While we
      did see improvement in anesthesiology residents' self-assessment, we did not see
      a similar effect on patient family, faculty or coworker evaluations.

PMID- 27687343
TI  - Low-dose butorphanol alleviates remifetanil-induced hyperalgesia in patients
      undergoing laparoscopic cholecystectomy.
AB  - OBJECTIVE: To evaluate the effects of low-dose butorphanol on hyperalgesia
      induced by high-dose remifetanil in patients undergoing laparoscopic
      cholecystectomy. DESIGN: Randomized double-blind clinical trial. SETTING:
      Intraoperative. PATIENTS: Seventy-five patients scheduled for laparoscopic
      cholecystectomy were enrolled. INTERVENTIONS: Randomly allocated into 3 groups,
      low dose of remifentanil (LR) group and high dose of remifentanil (HR) group
      received low (0.1MUg kg(-1) min(-1)) or high (0.3MUg kg(-1) min(-1)) doses of
      remifentanil, respectively, and butorphanol combined with remifentanil (BR) group
      received remifentanil (0.3MUg kg(-1) min(-1)) and butorphanol (0.2MUg/kg).
      MEASUREMENTS: The visual analog scale scores and cumulative consumption of
      fentanyl were recorded. MAIN RESULTS: Visual analog scale scores were
      significantly higher in the HR group than in the LR and BR groups (P<.001). The
      dose of intravenously given fentanyl was significantly higher in the HR group
      than in the LR and BR groups (P<.001). In addition, the HR group showed a
      significantly higher cumulative consumption of fentanyl during 5 to 8 hours after
      the operation (P<.001). CONCLUSIONS: A high dose of remifentanil induces
      postoperative hyperalgesia, which could be prevented by a continuous intravenous
      administration of a low dose of butorphanol.

PMID- 27687344
TI  - Dose-ranging effect of systemic diphenhydramine on postoperative quality of
      recovery after ambulatory laparoscopic surgery: a randomized, placebo-controlled,
      double-blinded, clinical trial.
AB  - STUDY OBJECTIVE: Diphenhydramine is an antihistamine with previously demonstrated
      analgesic and antiemetic properties. However, it is unknown if the beneficial
      perioperative properties of diphenhydramine can translate to a better quality of
      postsurgical recovery. The main objective of the current investigation was to
      investigate dose-ranging effects of diphenhydramine on quality of recovery after
      surgery. SETTING: Tertiary hospital in the United States. DESIGN: A prospective,
      randomized, double-blind trial. INTERVENTION: Saline, diphenhydramine 25 >mg, or
      diphenhydramine 50 mg given intravenously before induction. MEASUREMENTS: The
      primary outcome was global Quality of Recovery-40 at 24hours. Postoperative pain,
      nausea, opioid consumption, and discharge time were also evaluated. MAIN RESULTS:
      Ninety subjects were randomized, and 75 completed the study. The median
      (interquartile range) Quality of Recovery-40 scores were not different among
      study groups: 164 (151-189), 169 (159-181), and 172 (157-185) for the saline, 25
      mg diphenhydramine, and 50-mg diphenhydramine groups, respectively (P=.74).
      Postoperative nausea was decreased in the 50-mg group, 3 of 24 (12.5%), compared
      with the saline group, 12 of 27 (44%), P=.01. There was an inverse linear
      association between postoperative opioid consumption and quality of recovery
      (R(2)=0.37, P<.001). CONCLUSIONS: Diphenhydramine does not provide dose-ranging
      improvements on postoperative quality of recovery after ambulatory laparoscopic
      gynecologic surgery. Our results support a recent concept that not all
      postoperative nausea and vomiting symptoms are clinically important. Future
      studies evaluating postoperative nausea and vomiting should include patient
      centered outcomes to validate the clinical importance of the examined
      interventions.

PMID- 27687345
TI  - Cardiac arrest associated with takotsubo cardiomyopathy after tracheal
      intubation.

PMID- 27687346
TI  - Comparison of volume-controlled ventilation and pressure-controlled ventilation
      volume guaranteed during laparoscopic surgery in Trendelenburg position.
AB  - STUDY OBJECTIVE: To analyze the effects of pressure-controlled ventilation-volume
      guaranteed (PCV-VG) and volume controlled ventilation (VCV) on airway pressures
      and respiratory and circulatory indicators during laparoscopic surgery in
      Trendelenburg position. DESIGN: Prospective randomized comparative clinical
      study. SETTING: Tertiary hospital. PATIENTS: Forty ASA physical status 1 and 2
      patients who underwent elective laparoscopic surgery in Trendelenburg position.
      INTERVENTIONS: Patients were randomly allocated to either VCV group (n=20) or the
      PCV-VG group (n=20). After induction of anesthesia, for both modes of
      ventilation, the target tidal volume (VT) was 8mL/kg and the respiratory rate was
      adjusted to avoid hypercarbia. MEASUREMENTS: The peak and mean inspiratory
      pressures, dynamic compliance, exhaled VT, oxygenation index and physiological
      dead space were calculated and recorded at T1, 5minutes after induction of
      anesthesia in supine position, T2, 5minutes after stabilization of
      pneumoperitoneum, T3 and T4, 15 and 60minutes after 30 degrees  Trendelenburg
      position with pneumoperitoneum respectively. MAIN RESULTS: PCV-VG group had
      significantly lower peak inspiratory pressure and greater dynamic compliance than
      VCV group (P<.001). CONCLUSIONS: In patients who underwent laparoscopic surgery
      in Trendelenburg position, PCV-VG was superior to VCV in its ability to provide
      ventilation with lower peak inspiratory pressure and greater dynamic compliance.

PMID- 27687348
TI  - I have only D-blade: Is it enough?

PMID- 27687347
TI  - The effect of sugammadex on steroid hormones: A randomized clinical study.
AB  - STUDY OBJECTIVE: Sugammadex is an alternative drug to traditional decurarization
      by cholinesterase inhibitors. It has been examined the effect of sugammadex on
      steroid hormones in this study. DESIGN: Randomized clinical trial. SETTING: The
      study was conducted in a University Teaching Hospital from January 2013 to May
      2014. PATIENTS: Fifty male patients between 18 and 45years of age with an
      American Society of Anesthesiology (ASA) class I or II undergoing elective lower
      extremity surgery were included in this study. INTERVENTIONS: Patients were
      categorized into two groups (neostigmin group, Group N; and sugammadex group,
      Group S). In addition to standard monitorization, train-of-four (TOF) was also
      used to monitorize the level of neuromuscular blockade. Standard induction and
      maintenance of anesthesia were performed. At the termination of surgery,
      neuromuscular blockade was antagonized using 0.05mg/kg of neostigmine and
      0.01mg/kg of atropin when spontaneous recovery of neuromuscular blockade occurred
      with the reappearance of T2 in Group N and using 4mg/kg sugammadex in Group S.
      MEASUREMENTS: The primary outcome in this study was to determine serum
      aldosterone, cortisol, progesterone, and free testosterone levels. Three blood
      samples were obtained in each patient just before and 15minutes and 4hours after
      antagonism, MAIN RESULTS: No significant differences were found in demographic
      characteristics between the groups. While there were no differences in serum
      progesterone levels, patients in neostigmin group had significantly higher
      cortisol levels at 15minutes as compared to baseline. Also, patients in
      sugammadex group had significantly higher serum aldosterone and testosterone
      levels 15minutes after antagonism as compared to those in the neostigmine group.
      CONCLUSIONS: Our findings suggest that sugammadex is not associated with adverse
      effects on steroid hormones progesterone and cortisol, while it may lead to a
      temporary increase in aldosterone and testosterone.

PMID- 27687349
TI  - Stuck stylet situation: a rare manufacturing defect of spinal needle.

PMID- 27687350
TI  - Transversus abdominis plane block as a component of multimodal analgesia for
      laparoscopic cholecystectomy.
AB  - OBJECTIVE: To evaluate and compare intercostal-iliac transversus abdominis plane
      (TAP) and oblique subcostal TAP (OSTAP) blocks for multimodal analgesia in
      patients receiving laparoscopic cholecystectomy. DESIGN: A prospective,
      randomized, double-blinded clinical study. SETTING: Operating room, postoperative
      recovery area, and ward. PATIENTS: In total, 60 laparoscopic cholecystectomy
      patients (43 women, 17 men, American Society of Anesthesiologists grades I-II)
      were enrolled from the general surgery department of our tertiary care center.
      INTERVENTION: The patients were assigned to 1 of the 3 groups. Group 1 received
      TAP blocks (n=20), group 2 received OSTAP blocks (n=20), and group 3 patients
      were used as controls and received patient-controlled analgesia (PCA) only
      (n=20). After the induction of anesthesia, blocks were performed bilaterally in
      study groups 1 and 2, using 20mL of lidocaine (5mg/mL). PCA with intravenous
      tramadol was routinely provided for all patients during the first 24hours.
      MEASUREMENTS: The intraoperative use of remifentanil, postoperative visual analog
      scale (VAS) scores, demand for PCA, and total analgesic consumption were
      recorded. MAIN RESULTS: The patients in the control group had greater analgesic
      demands and analgesic consumption than did those in groups 1 and 2. However,
      patients in the OSTAP group had lower VAS scores than did those in groups 1 and
      3. RESULTS: The demand for analgesia was greater in the control group than in
      groups 1 and 2. Moreover, lower VAS scores were recorded in the OSTAP group than
      in groups 1 and 3 and were positively correlated with total PCA consumption among
      all patients. However, postoperative VAS scores were negatively correlated with
      the total intraoperative consumption of remifentanil at 24hours. CONCLUSIONS: TAP
      and OSTAP blocks improved postoperative analgesia in patients receiving
      laparoscopic cholecystectomy, which resulted in lower VAS scores and reduction in
      total analgesic consumption.

PMID- 27687351
TI  - New technique targeting the C5 nerve root proximal to the traditional
      interscalene sonoanatomical approach is analgesic for outpatient arthroscopic
      shoulder surgery.
AB  - STUDY OBJECTIVE: Regional anesthesia and analgesia for shoulder surgery is most
      commonly performed via interscalene nerve block. We developed an ultrasound
      guided technique that specifically targets the C5 nerve root proximal to the
      traditional interscalene block and assessed its efficacy for shoulder analgesia.
      DESIGN: Prospective case series. SETTING: Vanderbilt Bone and Joint Surgery
      Center. PATIENTS: Patients undergoing shoulder arthroscopy at an ambulatory
      surgery center. INTERVENTIONS: Thirty-five outpatient shoulder arthroscopy
      patients underwent an analgesic nerve block using a new technique where
      ultrasound visualization of the C5 nerve root served as the primary target at a
      level proximal to the traditional interscalene approach. The block was performed
      with 15mL of 0.5% plain ropivicaine. MEASUREMENTS: Post anesthesia care unit pain
      scores, opioid consumption, hand strength, and duration of block were recorded.
      Cadaver dissection after injection with methylene blue confirmed that the primary
      target under ultrasound visualization was the C5 nerve root. MAIN RESULTS: Pain
      scores revealed 97% patients had 0/10 pain at arrival to PACU, with 91% having a
      pain score of 3/10 or less at discharge from PACU. Medical Research Council (MRC)
      hand strength mean (SD) score was 4.17 (0.92) on a scale of 1-5. The mean (SD)
      duration of the block was 13.9 (3.5) hours. CONCLUSIONS: A new technique for
      ultrasound-guided blockade at the level of the C5 nerve root proximal to the
      level of the traditional interscalene block is efficacious for shoulder post
      operative pain control.

PMID- 27687352
TI  - Outpatient laparoscopic sleeve gastrectomy: first 100 cases.
AB  - STUDY OBJECTIVE: The development of outpatient surgery was one of the major goals
      of public health policy in 2010. The purpose of this observational prospective
      study was to evaluate the feasibility of laparoscopic sleeve gastrectomy (SG) in
      an ambulatory setting. DESIGN: Study design was a prospective prospective
      observational, nonrandomized study, registered (ClinicalTrials.gov identifier:
      NCT01513005), with institutional review board approval and written informed
      consent. SETTING: Amiens University Medical Center. PATIENTS: Patients undergoing
      SG who were preselected by inclusion ambulatory criteria. INTERVENTIONS: All
      patients operated on for obesity by laparoscopic SG, from May 2011 through July
      2013. MEASUREMENTS: We collected outcomes data on 100 patients including
      incidence of postoperative nausea and vomiting, maximum and average pain scores,
      and the overall satisfaction rate. MAIN RESULTS: Of the 100 obese patients, 93%
      were women. The mean age was 36 years (22-55 years). The mean preoperative body
      mass index was 42.4 kg/m(2). The mean operating time was 60 minutes (range, 30-95
      minutes). The overall satisfaction rate was 93% (n = 93). When leaving the
      postoperative care unit, 94% of patients felt no or mild pain. Eighty-two percent
      had no postoperative postoperative nausea and vomiting, and 7 patients needed
      treatment using ondasetron. CONCLUSIONS: Laparoscopic SG in an ambulatory setting
      is feasible with a dedicated anesthesiological approach and an expert surgical
      team. Appropriate patient selection is important for ensuring safety and quality
      of care within the outpatient program.

PMID- 27687353
TI  - Pectoralis-serratus interfascial plane block vs thoracic paravertebral block for
      unilateral radical mastectomy with axillary evacuation.
AB  - STUDY OBJECTIVE: The aim of this study was to evaluate the analgesic efficacy and
      safety of pectoralis-serratus interfascial plane block in comparison with
      thoracic paravertebral block for postmastectomy pain. DESIGN: A prospective
      randomized controlled study. SETTING: Tertiary center, university hospital.
      PATIENTS: Sixty-four adult women, American Society of Anesthesiologists physical
      status classes I, II, and III, scheduled for unilateral modified radical
      mastectomy with axillary evacuation. INTERVENTIONS: Patients were randomized to
      receive either pectoralis-serratus interfascial plane block, PS group (n=32), or
      thoracic paravertebral block, PV group (n=32). MEASUREMENTS: Twenty-four-hour
      morphine consumption and the time to rescue analgesic were recorded. The pain
      intensity evaluated by visual analog scale (VAS) score at 0, 2, 4, 8, 16, and
      24hours postoperatively was also recorded. MAIN RESULTS: The median
      (interquartile range) postoperative 24-hour morphine consumption was
      significantly increased in PS group in comparison to PV group (PS vs PV), 20 mg
      (16-23 mg) vs 12 mg (10-14 mg) (P<.001). The median postoperative time to first
      analgesic request was significantly shorter in PS group compared to PV group (PS,
      6 hours [5-7 hours], vs PV, 11 hours [9-13 hours]) (P<.001). The intensity of
      pain was low in both groups in VAS 0, 2, and 4hours postoperatively. However,
      there was significant reduction in VAS in PV group compared to PS group at 8, 16,
      and 24hours postoperatively. CONCLUSIONS: Pectoralis-serratus interfascial plane
      block was safe and easy to perform and decreased intensity of postmastectomy
      pain, but it was inferior to thoracic paravertebral block.

PMID- 27687354
TI  - The influence of patient position on withdrawal force of lumbar epidural
      catheters after total knee arthroplasty: A randomized trial.
AB  - STUDY OBJECTIVE: Elderly patients with degenerative knee disease may have
      accompanying degenerative spine conditions. There are no studies on lumbar
      epidural catheter withdrawal forces in these patients. The aim of this study was
      to investigate withdrawal forces and possible associated risk factors in patients
      undergoing total knee arthroplasty (TKA). DESIGN: Prospective randomized trial.
      SETTING: Operating room and ward in a university hospital. PATIENTS: Seventy
      eight patients aged 65 to 80years who were undergoing TKA and combined spinal
      epidural anesthesia were enrolled. INTERVENTIONS: Lumbar epidural catheterization
      was performed in a lateral position before surgery and the patients were randomly
      allocated to one of 3 positions for removal: flexed lateral (L), prone (P), and
      sitting (S). On the third postoperative day, the lumbar epidural catheters were
      removed by a single investigator with the patient in the assigned position.
      MEASUREMENTS: We measured the peak tension during catheter withdrawal and
      evaluated the factors affecting peak tension. MAIN RESULTS: The forces required
      to remove the catheters were considerably greater in the sitting and prone than
      in the flexed lateral position: group P (3.9N [0.28-10.36]), group S (4.1N [0.04
      11.57]), and group L (1.3N [0.07-3.65]) (P<.001). There was a positive
      correlation between the length of catheter in the epidural space and peak tension
      (P=.0026, beta coefficient=.223). CONCLUSIONS: For ease of removal of catheters
      from the lumbar epidural space, the flexed lateral position is recommended for
      elderly patients undergoing TKA. When placing the epidural catheter, the
      physician should be careful not to insert a catheter that is excessively long.

PMID- 27687355
TI  - Entropy vs standard clinical monitoring using total intravenous anesthesia during
      transvaginal oocyte retrieval in patients for in vitro fertilization.
AB  - STUDY OBJECTIVE: Day care surgery is an important arena for monitors of
      anesthetic depth where minimizing drug use is essential for rapid turnover.
      Underdosage, on the other hand, carries the risks of intraoperative awareness and
      pain. Transvaginal oocyte retrieval (TVOR), often performed under total
      intravenous anesthesia using propofol and fentanyl in Indian patients, is a
      procedure of special interest because, in addition to the above concerns, toxic
      effects of propofol on oocytes have been described. We have studied the role of
      entropy monitor, a depth of anesthesia monitor, in optomising drug titration and
      facilitating distinction between analgesic and hypnotic components of anesthesia.
      DESIGN: Prospective randomized controlled study. SETTING: Operating theater and
      postoperative recovery area. PATIENTS: One hundred twenty American Society of
      Anesthesiologists class I and II female patients coming to the IVF centre for
      TVOR under total intravenous anesthesia using propofol and fentanyl. They were
      randomly allocated into 2 groups: Group EM (drugs titrated as per entropy values:
      state entropy and response entropy) and group CM (drugs titrated as per standard
      clinical monitoring). INTERVENTION: None. MEASUREMENTS: Total propofol
      consumption (TP), total fentanyl consumption (TF), on-table recovery time (T1),
      time to discharge (T2), intraoperative awareness (A). MAIN RESULTS: Patients in
      group EM demonstrated 6.7% lesser consumption of propofol (P= .01), 10.9% more
      consumption of fentanyl (P= .007) and 1 minute faster recovery on-table (P= .009)
      as compared to group CM. In the PACU, only 10% patients of group EM required
      supplemental analgesia as opposed to 28.3% in CM group (P= .01). Time to
      discharge was similar in both groups and no intraoperative awareness was noted.
      CONCLUSION: Entropy monitor is a useful tool allowing distinction between
      analgesic and hypnotic components of general anesthesia in patients undergoing
      TVOR and facilitating drug titration accordingly. Its impact on intraoperative
      awareness needs to be further evaluated.

PMID- 27687356
TI  - Educational review of Perioperative Medicine for the Junior Clinician.

PMID- 27687357
TI  - Regional anesthesia practice in China: a survey.
AB  - STUDY OBJECTIVE: Neuraxial anesthesia has been widely used in China. Recently,
      Chinese anesthesiologists have applied nerve stimulator and ultrasound guidance
      for peripheral nerve blocks. Nationwide surveys about regional anesthesia
      practices in China are lacking. We surveyed Chinese anesthesiologists about
      regional anesthesia techniques, preference, drug selections, complications, and
      treatments. DESIGN: A survey was sent to all anesthesiologist members by WeChat.
      The respondents can choose mobile device or desktop to complete the survey. Each
      IP address is allowed to complete the survey once. MAIN RESULTS: A total of 6589
      members read invitations. A total of 2654 responses were received with fully
      completed questionnaires, which represented an overall response rate of 40%.
      Forty-one percent of the respondents reported that more than 50% of surgeries in
      their hospitals were done under regional anesthesia. Most of the participants
      used test dose after epidural catheter insertion. The most common drug for test
      dose was 3-mL 1.5% lidocaine; 2.6% of the participants reported that they had
      treated a patient with epidural hematoma after neuraxial anesthesia. Most
      anesthesiologists (68.2%) performed peripheral nerve blocks as blind procedures
      based on the knowledge of anatomical landmarks. A majority of hospitals (80%) did
      not stock Intralipid; 61% of the respondents did not receive peripheral nerve
      block training. CONCLUSIONS: The current survey can serve as a benchmark for
      future comparisons and evaluation of regional anesthesia practices in China. This
      survey revealed potential regional anesthesia safety issues in China.

PMID- 27687358
TI  - The role of intraoperative transesophageal echocardiographic monitoring in a
      patient with hypertrophic cardiomyopathy undergoing laparoscopic surgery.
AB  - Hypertrophic cardiomyopathy (HCM) presents a significant perioperative challenge.
      Anesthetic drugs, patient positioning, and surgical technique can provoke
      worsening left ventricular outflow tract obstruction and hemodynamic
      deterioration. In this case report, we present the perioperative management of a
      70-year-old male with a history of HCM who underwent a robotic laparoscopic
      prostatectomy. Discussion focuses on the utilization of echocardiographic
      guidance in the care of patients with HCM undergoing noncardiac surgery, as well
      as the pathophysiology of laparoscopic insufflation and its effects on left
      ventricular outflow tract obstruction in HCM. 

PMID- 27687359
TI  - A comparison of prophylactic use of meperidine, meperidine plus dexamethasone,
      and ketamine plus midazolam for preventing of shivering during spinal anesthesia:
      a randomized, double-blind, placebo-controlled study.
AB  - STUDY OBJECTIVES: The aim of this study is to compare the efficacy of combination
      of meperidine and dexamethasone with that of placebo, meperidine alone, and the
      combination of ketamine and midazolam in preventing shivering during spinal
      anesthesia. DESIGN: This is a prospective, placebo-controlled study. SETTING: The
      setting is at an operating room of a university-based teaching hospital.
      PATIENTS: Two hundred American Society of Anesthesiologists I and II patients
      undergoing orthopedic and urologic surgery under spinal anesthesia were included.
      INTERVENTIONS: Subarachnoid anesthesia was performed by using 15mg of 0.5%
      hyperbaric bupivacaine. Patients were randomly allocated to receive saline
      (placebo, group C), meperidine 0.4mg/kg (group Me), ketamine 0.25mg/kg plus
      midazolam 37.5MUg/kg (group KMi), and meperidine 0.2mg/kg plus dexamethasone
      0.1mg/kg (group MeD). All drugs were given as an intravenous bolus immediately
      after intrathecal injection. MEASUREMENTS: During surgery and stay in the
      recovery room, shivering score, blood pressure, and some other adverse effects
      were recorded at 5-minute intervals. Axillary and tympanic temperatures were
      recorded at 15-minute intervals during the perioperative period. MAIN RESULTS:
      The incidence of shivering after 30minutes of spinal anesthesia in groups C, Me,
      KMi, and MeD was 64%, 20%, 20%, and 4%, respectively, which was significantly
      higher in group C compared with other groups (P<.0001). Regarding adverse
      effects, there was no significant difference between groups (P>=.2). Axillary
      temperature significantly increased in the 15th-120th-minute interval in groups
      Me, KMi, and MeD (P<.0001) and in group MeD was higher than that in other groups.
      Core temperature decreased in the 15th-120th-minute interval in group MeD, lower
      than that in other groups (P<.0001). CONCLUSIONS: Prophylactic use of meperidine
      0.2mg/kg plus dexamethasone 0.1mg/kg was more effective than meperidine 0.4mg/kg
      as a sole agent or the combination of ketamine 0.25mg/kg and midazolam 37.5MUg/kg
      in preventing shivering resulting from spinal anesthesia.

PMID- 27687360
TI  - Comparison of dexamethasone or intravenous fluids or combination of both on
      postoperative nausea, vomiting and pain in pediatric strabismus surgery.
AB  - BACKGROUND: Strabismus surgery is perhaps a pediatric surgical procedure that has
      the strongest evidence of postoperative nausea and vomiting (PONV) risk. This
      randomized controlled blind study was designed to evaluate the efficacy of
      combined therapy of dexamethasone and intraoperative superhydration vs their
      monotherapy on the incidence and severity of PONV and on pain intensity after
      pediatric strabismus surgery. METHODS: A total of 120 children aged 6 to 12 years
      undergoing strabismus surgery were randomized to equally 3 groups to receive 0.15
      mg/kg dexamethasone (dexamethasone group) or intraoperative superhydration of
      lactated Ringer's solution in a dose of 30 mL/kg per fasting time (superhydration
      group), or a combination of dexamethasone and intraoperative fluid in the same
      strategy (combination therapy group). The incidence and severity of PONV and pain
      using visual analog scale score, and need for supplemental antiemetic and
      analgesic therapy and their consumptions were assessed and compared in the 3
      studied groups for 24 hours postoperatively. RESULTS: The incidence of PONV and
      postoperative vomiting was significantly lower (P> .001) in the combination
      therapy group (5% and 5% respectively) compared with the dexamethasone group (35%
      and 30%) and superhydration group (32.5% and 35%). There was no significant
      difference among patients in the superhydration group and dexamethasone group in
      the cumulative incidences of PONV in the whole 24 hours postoperatively.
      Postoperative aggregated visual analog scale pain score and total acetaminophen
      consumption showed a significant reduction (P> .05) in the combination therapy
      group together with significant prolongation of time to the first analgesic
      request compared with both the superhydration group and the dexamethasone group.
      CONCLUSION: Combined therapy of 0.15 mg/kg dexamethasone 1 minute before
      induction and intraoperative fluid superhydration is an effective and safe way to
      reduce PONV and pain better than monotherapy of dexamethasone, or intraoperative
      superhydration separately for pediatric strabismus surgery.

PMID- 27687361
TI  - Postoperative muscular cramp caused by lower limb ischemia related to the
      unilateral popliteal arteriovenous fistula.

PMID- 27687362
TI  - LMA-ProSeal insertion by novice doctors as affected by a 90 degrees  bend created
      by an intubating stylet: a randomized clinical trial.
AB  - STUDY OBJECTIVE: This study aimed to test the hypothesis that insertion of the
      supraglottic device LMA-ProSeal (ProSeal) by novice doctors in anesthetized
      patients can be improved by using an intubating stylet to create a 90 degrees 
      bend and that better sealing pressure is achieved. DESIGN: Randomized clinical
      trial. SETTING: Operating room. PATIENTS: Seventy adult patients scheduled for
      elective surgery under general anesthesia using ProSeal with American Society of
      Anesthesiologists physical status 1 to 3. INTERVENTIONS: ProSeal were inserted
      with the 90 degrees  bend created by the intubating stylet (90D group, 35
      patients) or not (ie, conventional insertion; C group, 35 patients).
      MEASUREMENTS: The number of attempts to successful insertion, sealing pressure,
      subjective difficulty of insertion by novice doctors, and postoperative
      pharyngeal pain or hoarseness were compared between groups. MAIN RESULTS: The
      total number of insertion attempts for the 90D and control groups were 1 (24 and
      8, respectively), 2 (8 and 13), 3 (3 and 9), and failure (0 and 5), respectively,
      showing significant differences between groups (P<.001). Sealing pressure was
      significantly higher in the 90D group than in the C group (90D group, 23.3+/
      3.7cm H2O; C group, 19.5+/-2.6cm H2O; P<.001), and the subjective difficulty of
      insertion was significantly lower in the 90D group (90D group, 27.3+/-17.6mm; C
      group, 55.4+/-22.8mm; P<.001). The incidence of postoperative pharyngeal pain and
      hoarseness did not differ significantly between groups. CONCLUSIONS: Our results
      suggest that creating a 90 degrees  bend using an intubating stylet facilitates
      ProSeal insertion by novice doctors, as reflected by higher successful insertion
      rates, higher sealing pressure, and lower subjective difficulty of insertion in
      anesthetized patients.

PMID- 27687363
TI  - Difficult airway in Mowat-Wilson syndrome.
AB  - Mowat-Wilson syndrome is a rare congenital syndrome involving multiple system
      abnormalities. The most consistently present components include facial deformity,
      mental retardation, and Hirschsprung disease. We report the anesthetic management
      of a case of Mowat-Wilson syndrome, with a difficult airway, who underwent
      Duhamel's procedure and colostomy closure. 

PMID- 27687364
TI  - Continuous epidural pumping of saline contributes to prevent and treat postdural
      puncture headache.
AB  - STUDY OBJECTIVE: Postdural puncture headache (PDPH) is the most common symptom of
      accidental dural puncture, a frequent complication of intraspinal anesthesia. We
      developed a postoperative intervention technique to prevent and treat PDPH in
      accidental dural puncture patients, including epidural pumping of saline. This
      retrospective study aimed to retrospectively evaluate this new technique for PDPH
      prevention and treatment. DESIGN: Retrospective study. SETTING: Beijing
      Obstetrics and Gynecology Hospital affiliated to the Capital Medical University,
      between January 2006 and December 2012. PATIENTS: Eighty-seven cases undergoing
      intraspinal anesthesia were assessed. INTERVENTIONS: Of these patients, 68 cases
      had successful repuncture and were assigned to group A (epidural filling group,
      n=68), receiving continuous epidural pumping of 0.9% NS (150mL) at a rate of
      6mL/h; the remaining cases were assigned to group B (conservative therapy group,
      n=19). MEASUREMENTS: Age, height, and body weight were collected, and
      postoperative headache was assessed using a visual analog scale. MAIN RESULTS: Of
      68 patients in group A, 49 (72.1%) developed PDPH, whereas all in group B
      developed PDPH (P=.009). In addition, all patients showed PDPH within 3days after
      surgery regardless of treatment group. However, a statistically significant
      difference was obtained for PDPH duration between groups A and B (P<.001).
      Multivariate logistic regression analysis showed that frequency of epidural
      puncture and continuous epidural pumping of saline were significant risk factors
      for PDPH. CONCLUSIONS: Our data indicated that application of 6mL/h saline
      effectively contributes to PDPH management, and its clinical application should
      be broadened.

PMID- 27687365
TI  - Sonographic evaluation of lumbar interlaminar space opening in a variety of
      patient body positions for optimal neuraxial anesthesia delivery.
AB  - OBJECTIVE: To find the position that provided the most comfort, as well as the
      widest L3-L4 interlaminar space opening. DESIGN: Pilot study. SETTING: Operating
      room. PATIENTS: Thirty-two healthy volunteers. INTERVENTIONS: L3-L4 interlaminar
      space was measured on volunteers assuming a baseline position (sitting upright)
      and 5 study positions: (1) sitting in fetal position, (2) sitting on a table
      tilted at 30 degrees , (3) sitting while hugging an exercise ball, (4) sitting
      with midcalves on the table's edge, and (5) lying on one side in fetal position.
      Interlaminar spaces were measured to determine which position resulted in the
      largest interlaminar space compared with baseline. The comfort level of each
      position was rated by subjects using a visual analogue scale from 1 to 10. MAIN
      RESULTS: The means of the interlaminar openings in all study positions were
      significantly different from baseline, with the "sitting fetal" having the
      greatest difference, (1.32mm, P<.001), followed by "hugging a ball" (0.94mm,
      P<.001) and "lying fetal" (0.92mm, P<.001). Alternatively, when using "sitting
      fetal" (a more commonly used position) as a comparative baseline, "hugging a
      ball" and "lying fetal" showed smaller but not significantly different
      interlaminar openings (Delta=-0.38mm, P value = .221 and Delta=-0.40mm, P value =
      .164, respectively)."Sitting on a tilted table" and "sitting midcalf" showed
      significantly smaller interlaminar openings (Delta=-0.52mm, P value = .025 and
      Delta=-0.72mm, P value < .001, respectively) when compared with the alternative
      baseline of "sitting fetal." Mean visual analogue scale scores for comfort showed
      that "hugging a ball" (7.8/10), "lying fetal" (7.5/10), and "sitting fetal"
      (7.2/10) positions had the highest ratings. CONCLUSIONS: Ultrasonographic
      measurements carried out on 32 subjects showed that "sitting fetal," "lying
      fetal," and "hugging a ball" positions provided the widest L3-L4 interlaminar
      openings. These 3 positions were also found to be more comfortable.

PMID- 27687367
TI  - Clinical experiences of laser Doppler blood flow sensor for thoracic
      paravertebral nerve block.

PMID- 27687366
TI  - Randomized comparison of the feasibility of three anesthetic techniques for day
      case open inguinal hernia repair.
AB  - STUDY OBJECTIVE: Comparison of local anesthetic infiltration (LAI), spinal
      anesthesia (SPIN) and total intravenous anesthesia (TIVA) for open inguinal
      herniorrhaphy. We hypothesized that patients receiving LAI could be discharged
      faster than SPIN and TIVA patients. DESIGN: Randomized, prospective trial.
      SETTING: University hospital day-surgery center. PATIENTS: 156 adult male
      patients (ASA 1-3) undergoing day-case open inguinal herniorrhaphy.
      INTERVENTIONS: Patients were randomized to either LAI (lidocaine+ropivacaine),
      SPIN (bupivacaine+fentanyl) or TIVA (propofol+remifentanil). Perioperative Ringer
      infusion was 1.5mL/h. Urinary bladder was scanned before and after surgery.
      Interviews were performed on postoperative days 1, 7 and 90. MEASUREMENTS:
      Duration of surgery, duration of the patients' stay in the operating room and
      time until their readiness for discharge home. Patient satisfaction and adverse
      effects were registered. MAIN RESULTS: Surgery lasted longer in LAI group (median
      40min) than in SPIN group (35min) (P=.003) and TIVA group (33min) (P<.001).
      Although surgery was shortest in TIVA group, TIVA patients stayed longer in the
      operating room than LAI patients (P=.001). Time until readiness for discharge was
      shorter in LAI group (93min) than in TIVA (147min) and SPIN (190min) groups
      (P<.001). Supplementary lidocaine infiltration was given to 32 LAI patients, and
      IV fentanyl to 29 LAI and 4 SPIN patients. Ephedrine was required in 34 TIVA, 5
      LAI and 5 SPIN patients. One SPIN and three LAI patients had to be given TIVA and
      another SPIN patient LAI to complete the operations. Urinary retention was
      absent. Discomfort in the scar (26%) three months postoperatively was not
      anesthesia-related. CONCLUSIONS: Logistically, LAI was superior because of the
      fastest recovery postoperatively. The anesthetic techniques were adequate for
      surgery in all but a few LAI and SPIN patients. Lack of urinary retention was
      probably related to the small IV infusion volumes.

PMID- 27687368
TI  - Clinical settings of arterial catheter's insertion with new infrared device
      "MillSuss".

PMID- 27687369
TI  - Magnesium sulfate or diltiazem as adjuvants to total intravenous anesthesia to
      reduce blood loss in functional endoscopic sinus surgery.
AB  - STUDY OBJECTIVE: This study was designed to know whether addition of magnesium
      sulfate (MgSO4) or diltiazem to total intravenous anesthesia (TIVA) (propofol)
      aided reduction in blood loss during functional endoscopic sinus surgery (FESS).
      The secondary outcomes measured were surgeon's assessment of the surgical field
      and hemodynamics. DESIGN: Randomized, double-blinded, placebo-controlled trial.
      SETTING: Operating room. PATIENTS: Forty-five American Society of
      Anesthesiologists I and II adult patients (18-60years) undergoing FESS.
      INTERVENTIONS: All groups received propofol-fentanyl TIVA. Patients were randomly
      allocated to 1 of the 3 groups (MgSO4 group, n=15; diltiazem group, n=15; saline
      group, n=15). MEASUREMENTS: Intraoperative bleeding was quantified, and quality
      of surgical field was graded. Hemodynamic parameters were recorded. MAIN RESULTS:
      Addition of both MgSO4 and diltiazem significantly reduced blood loss (240 and
      350mL) in comparison to control group (415mL) (P=.003). The surgical field was
      significantly better in the MgSO4 group compared with the diltiazem (P=.028) and
      saline groups (P=.0001). CONCLUSION: It was concluded that the addition of both
      MgSO4 and diltiazem to TIVA propofol results in significant reduction in blood
      loss and significant improvement in the quality of surgical field during FESS
      without causing any adverse effects on the hemodynamics or on the recovery from
      anesthesia. The surgical field in the MgSO4 group was significantly better than
      that in the diltiazem group (P=.04).

PMID- 27687370
TI  - Rocuronium is associated with an increased risk of reintubation in patients with
      soft tissue infections.
AB  - STUDY OBJECTIVE: To determine risk factors associated with reintubations in adult
      patients with soft tissue infections. DESIGN: A retrospective case-control
      design. SETTING: Operating room and postoperative recovery area. PATIENTS: There
      were 39 patients who presented for surgical intervention of their soft tissue
      infection and 222 controls having general surgery who were matched for age, sex,
      and body mass index. All patients were older than the age of 18 years and mostly
      American Society of Anesthesiologists physical status of III to IV and presented
      to our level 1 trauma center. INTERVENTIONS: Reintubation within 2 hours after
      planned extubation. MEASUREMENTS: The following data were collected: reintubation
      rates, train of four ratio, reversal agents, age, sex, creatinine, smoking
      history, transfusion requirements, Sequential Organ Failure Assessment score,
      hemoglobin, and lactate. MAIN RESULTS: The use of rocuronium was independently
      associated with increased odds of reintubation. Patients with a higher train of
      four ratio were more likely to be reintubated and less likely to be reversed as
      compared to those with a lower train of four ratio. CONCLUSIONS: Soft tissue
      patients who have received rocuronium are at increased risk for reintubation,
      particularly those with renal failure. In addition, this article supports the use
      of neuromuscular blockade reversals, even in patients with a strong train of four
      ratio.

PMID- 27687371
TI  - Video-assisted thoracoscopic surgery in an adult moyamoya disease case.

PMID- 27687372
TI  - Transnasal sphenopalatine ganglion block for the treatment of postdural puncture
      headache in obstetric patients.
AB  - STUDY OBJECTIVE: To demonstrate a possible alternative treatment for postdural
      puncture headache (PDPH). DESIGN: Postdural puncture headache is a common
      complication associated with neuraxial anesthesia and unintentional dural
      puncture. Epidural blood patch (EBP) is the standard therapy for PDPH but has
      risks including pain, dural puncture, and infection. Transnasal sphenopalatine
      ganglion block (SPGB) has been successfully used to treat migraine, cluster
      headache, and trigeminal neuralgia. This is a small case series in which SPGB was
      used to treat PDPH in 3 obstetric patients. SETTING: Labor and delivery suite.
      PATIENTS: Three postpartum patients with PDPH were studied. One patient was
      American Society of Anesthesiologists physical status 1, and the other 2 were
      American Society of Anesthesiologists physical status 2. INTERVENTIONS:
      Transnasal SPGB using cotton-tipped applicators and 2% viscous lidocaine was
      performed on all 3 patients. MEASUREMENTS: Height, weight, and vital signs were
      measured on all patients. In addition, the numeric rating scale (0-10) was used
      to quantify the pain level while in the sitting position preprocedure,
      immediately postprocedure, 24 hours postprocedure, and 48 hours postprocedure.
      MAIN RESULTS: All 3 patients had significant pain relief following the SPGB
      without the need for EBP. CONCLUSIONS: When comparing the risks of a transnasal
      SPGB, which include bleeding and temporary discomfort, against those of an EBP,
      which are documented as dural puncture, neurologic complications, bleeding, and
      infection, it seems reasonable to offer the SPGB before EBP.

PMID- 27687373
TI  - Effect of depth of neuromuscular blockade on the abdominal space during
      pneumoperitoneum establishment in laparoscopic surgery.
AB  - STUDY OBJECTIVE: To evaluate the effect of neuromuscular blockade (NMB) upon the
      abdominal space during pneumoperitoneum establishment in laparoscopic surgery,
      comparing moderate NMB and deep NMB. DESIGN: Prospective, randomized, crossover
      clinical trial. SETTING: Operating room. PATIENTS: Seventy-six American Society
      of Anesthesiologists 1 to 2 patients scheduled for elective laparoscopic surgery.
      INTERVENTIONS: Two independent evaluations were performed at the establishment of
      pneumoperitoneum for a preset intraabdominal pressures (IAPs) of 8 and 12 mm Hg,
      both during moderate NMB (train-of-four count, 1-3) and deep NMB (posttetanic
      count, <5). Rocuronium was used to induce NMB, and sugammadex was used for
      reversal. MEASUREMENTS: We evaluated (i) the volume of CO2 introduced in 41
      patients and (ii) the skin-sacral promontory distance in 35 patients, at
      pneumoperitoneum establishment. RESULTS: Compared to moderate NMB, deep NMB
      increased, in a significant manner, both the intraabdominal volume of CO2
      insufflated (mean [SD], 2.24 [1.10] vs 2.81 [1.13] L at 8 mm Hg IAP, P<.001, and
      3.52 [1.31] vs 4.09 [1.31] L at 12 mm Hg IAP, P<.001) and the skin-sacral
      promontory distance (11.78 [1.52] vs 12.16 [1.51] cm at 8 mm Hg IAP, P=.002, and
      13.34 [1.87] vs 13.80 [1.81] cm at 12 mm Hg IAP, P<.001). Increase in
      intraabdominal volume after inducing deep NMB was observed in 88% and 81.7% of
      patients at 8 and 12 mm Hg pneumoperitoneum, with a volume increase of mean of
      36.8% (95% confidence interval [CI], 22.8-50.8) and 25% (95% CI, 13.7-36.4),
      respectively (P=.003). Increase in distance was observed in 61% and 82% of
      patients at 8 and 12 mm Hg pneumoperitoneum, with a mean distance increase of
      3.3% (95% CI, 1.3-5.4) and 3.6% (95% CI, 1.9-5.2), respectively (P=.840).
      CONCLUSIONS: Deep NMB, in comparison to moderate NMB, increased in a significant
      manner the abdominal space at pneumoperitoneum establishment. However, the
      effective increase in the abdominal cavity dimensions could be low, the increase
      showed a great interindividual variability, and it was not observed in every
      patient. Clinical significance of this increase on surgical conditions is yet to
      be demonstrated.

PMID- 27687374
TI  - Probe's fixation during ultrasound-guided Central Venous puncture by using the
      echosupport.

PMID- 27687375
TI  - Successful cases of thyroid surgery performed under only bilateral cervical
      plexus blocks.

PMID- 27687376
TI  - Interesting "VIA" mnemonic for airway management.

PMID- 27687377
TI  - A randomized trial comparing prophylactic phenylephrine and ephedrine infusion
      during spinal anesthesia for emergency cesarean delivery in cases of acute fetal
      compromise.
AB  - BACKGROUND: Previous evidence showed that use of phenylephrine was associated
      with higher umbilical artery pH (UA pH) than ephedrine after elective cesarean
      delivery (CD). However, the best choice of vasopressor and its effect on funic
      gases in cases of acute fetal compromise require additional studies. METHODS:
      Ninety parturients showing acute fetal compromise during intrapartum period and
      taken up for CD (category II) under spinal anesthesia were randomized to receive
      prophylactic infusion of ephedrine 2.5mg/min or phenylephrine 30MUg/min. Systolic
      blood pressure was targeted between 90% and 110% of baseline. Incidence of fetal
      acidosis (UA pH <7.2 and/or base deficit >12mmol/L) was recorded. Other
      parameters of cord gases, Apgar score, need for immediate resuscitation, maternal
      hemodynamics, and adverse events were also compared. RESULTS: Number of neonates
      showing acidosis with ephedrine or phenylephrine was comparable (P=.22). Of
      these, newborns with base deficit >12mmol had low 1-minute Apgar scores
      (n=15/23). The ephedrine group had higher oxygen content in UA (P=.03). There was
      no adverse neonatal outcome during the period of observation. Incidence of
      maternal nausea and vomiting was higher with ephedrine than with phenylephrine
      (22.2% vs 4.4%; P=.02). Maternal bradycardia was observed with phenylephrine
      (P=.02). CONCLUSION: Our data report similar fetal acidosis with either
      phenylephrine or ephedrine administered during spinal anesthesia for treating
      maternal hypotension in cases of emergency CD.

PMID- 27687378
TI  - Comparing the efficacy and safety between propofol and dexmedetomidine for
      sedation in claustrophobic adults undergoing magnetic resonance imaging (PADAM
      trial).
AB  - STUDY OBJECTIVE: To determine the efficacy of sedation with dexmedetomidine
      compared to propofol for claustrophobic adults undergoing magnetic resonance
      imaging (MRI) in our institution. DESIGN: Randomized, prospective, double-blinded
      study. SETTING: University-based tertiary referral center. PATIENTS: Thirty
      claustrophobic adults with American Society of Anesthesiologists physical status
      I and II who were planned for MRI. INTERVENTIONS: Patients were randomly assigned
      to target-controlled infusion propofol or dexmedetomidine loading followed by
      maintenance dose for procedural sedation. MEASUREMENTS AND MAIN RESULTS: The
      primary end point was adequate reduction in patient anxiety levels to allow
      successful completion of the MRI sequence. Both methods of sedation adequately
      reduced anxiety levels in visual analog scale scores and Spielberger Strait Test
      Anxiety Inventory (P<.001). Dexmedetomidine required a longer time to achieve
      anxiolysis, 7.36minutes (SD, 2.59), and required increasing maintenance dose to
      induce sleep compared to 10.71minutes (SD, 4.63) for propofol. In terms of image
      quality, 2 patients (16.67%) in the dexmedetomidine group were satisfactory,
      whereas all with propofol were graded as good to excellent. Adverse effects were
      seen in patients sedated with dexmedetomidine with number needed to harm 8 for
      hypotension and 15 for bradycardia compared to none recorded in the propofol arm.
      There was no significant difference in patient satisfaction scores or home
      readiness after the MRI. CONCLUSIONS: Both dexmedetomidine and propofol can
      effectively reduce anxiety levels of claustrophobic adults undergoing MRI, but
      dexmedetomidine takes longer to achieve adequate anxiolysis and sleep and may
      have an effect on image quality. Hypotension and bradycardia are common adverse
      effects observed with dexmedetomidine.

PMID- 27687379
TI  - Comparison of the clinical performances of Air-Qsp and i-Gel for airway
      management under general anesthesia with a muscle relaxant.
AB  - STUDY OBJECTIVES: Recently, i-Gel intubating laryngeal airway (ILA) has been
      frequently used because of the ease for airway insertion by residents and young
      anesthesiologists. However, it sometimes fails to fit or ventilate sufficiently
      in Japanese patients. Use of Air-Qsp, which is a new non-inflatable cuffed ILA,
      in a clinical setting has become possible. The purpose of this study was to
      compare the clinical performance of Air-Qsp with that of i-Gel for airway
      management in Japanese adult patients. DESIGN: A randomized, single-blinded,
      prospective study was conducted after approval from the institutional review
      board. SETTING: Operating rooms at hospitals. PATIENTS: Thirty-seven adult
      patients aged 20 to 69 years, with ASA physical status I or II, and scheduled for
      elective surgery under general anesthesia in the supine position. INTERVENTIONS:
      Patients were randomly assigned to insertion with Air-Qsp (Group A: n=20) or i
      Gel (Group I: n=17). MEASUREMENTS: The number of insertions, duration of
      insertion, changes in systolic blood pressure and heart rate during insertion,
      delivered tidal volume for setting volume control ventilation, distribution of
      the tips of the bronchofiberscopes (BFs) on a clock face, and the number of
      postoperative complications was evaluated. MAIN RESULTS: Two patients in Group A
      and one patient in Group I were excluded because insertion of the device failed.
      There were no significant differences in measured parameters between the 2
      groups. The distribution of the tips of the bronchofiberscopes tended to be
      around the center of the glottis in Group A, whereas they were more toward the 6
      o'clock position in Group I. CONCLUSIONS: Air-Qsp is as useful as i-Gel in
      Japanese patients and the distributions of the tips of BFs through ILAs are
      different for Air-Qsp and i-Gel.

PMID- 27687380
TI  - Dose of intraoperative remifentanil administration is independently associated
      with increase in the risk of postoperative nausea and vomiting in elective
      mastectomy under general anesthesia.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the common
      complications in patients who have undergone surgery with general anesthesia. The
      association of intraoperative use of remifentanil with PONV has remained
      controversial. The aim of the current study was to determine the association of
      dose of intraoperative remifentanil administration with incidence of PONV.
      METHODS: The present study was a single-center retrospective observational study
      and included 423 female patients with American Society of Anesthesiologists
      physical status I or II who underwent elective mastectomy under general
      anesthesia between October 2011 and October 2012. The incidence of PONV within 3
      days after the operation was prospectively assessed. The time-weighted average of
      remifentanil during the operation (twRem) was calculated. We used a multivariate
      regression model to assess the independent association of the twRem with the
      incidence of PONV. RESULTS: Among 423 patients, 129 patients (30.5%) had PONV
      during the study period. Remifentanil was administrated in 355 patients (83.9%).
      In the multivariate logistic regression model using categories of twRem, we found
      that increased twRem was independently associated with increase in the risk of
      PONV (P=.01). There was an independent association between twRem greater than 0.2
      MUg/kg per minute and increase in the risk of PONV. CONCLUSION: This
      retrospective observational study revealed a dose-dependent association between
      dose of intraoperative remifentanil administration and increase in the risk of
      PONV. Time-weighted average of remifentanil greater than 0.2 MUg/kg per minute
      was independently associated with risk of PONV.

PMID- 27687381
TI  - Perioperative factors associated with Hospital Consumer Assessment of Healthcare
      Providers and Systems responses of total hip arthroplasty patients.
AB  - OBJECTIVE: To determine perioperative treatments and events associated with
      Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS)
      responses among patients who undergo total hip arthroplasties (THAs) and total
      knee arthroplasties (TKAs). DESIGN: Retrospective analysis. SETTING: Single
      tertiary care, academic, urban, level 1 trauma center. PARTICIPANTS: Final cohort
      represents 301 consecutive surgical inpatients meeting criteria for evaluation by
      HCAHPS survey. EXPOSURES: Responses to 4 HCAHPS questions were analyzed against
      perioperative treatments and events. MEASURES: Positive and negative responses to
      HCAHPS questions. RESULTS: THA patients responding affirmatively to both pain
      specific and general satisfaction were associated with preoperative use of
      chronic nonsteroidal anti-inflammatory drugs. In addition, THA patients
      responding affirmatively "how often was your pain well controlled" were also
      associated decreased postanesthesia care unit (PACU) opioid requirement. TKA
      patients responding affirmatively to "what number would you use to rate this
      hospital" were associated with shorter PACU stays and lower final pain scores.
      TKA patients responding affirmatively to "would you recommend this hospital to
      your family" were associated with shorter lengths of stay in the hospital and in
      the PACU. TKA patients responding affirmatively to "How often did the hospital
      staff do everything to help with your pain" were not associated with any measured
      perioperative event. TKA patients responding affirmatively to "how often was your
      pain well controlled" were associated with older age, decreased use of
      preoperative chronic benzodiazepines, and increased use of preoperative
      midazolam. CONCLUSIONS: These data suggest that chronic use of nonsteroidal anti
      inflammatory drugs is associated with improved overall satisfaction and
      satisfaction with pain in THA patients. Furthermore, increased PACU opioid use
      was negatively associated satisfaction with pain management. Age, lengths of stay
      preadmission medications, anxiolytic medications, and PACU pain scores are
      associated with patient satisfaction with regards to both pain management and
      overall satisfaction in TKA patients.

PMID- 27687382
TI  - Iterative epidural blood patch for recurrent spontaneous intracranial hypotension
      during pregnancy.
AB  - A 30-year-old woman at 28 weeks presented with sudden onset of intense headache,
      epigastric pain, hot flushes, nausea, vomiting, and stiff neck. Cerebral magnetic
      resonance imaging showed pathognonomic signs of spontaneous intracranial
      hypotension (SIH). Epidural blood patch was performed 2 times during pregnancy
      for symptoms relief in spite of medical treatments. No other recurrence was noted
      until the spontaneous delivery. SIH is a rare entity during pregnancy which may
      be diagnosed using magnetic resonance imaging. Iterative Epidural blood patch
      should be proposed to patients with SIH during pregnancy because it allowed
      faster symptoms improvement and patient relief with complete recovery than
      medical treatment only. 

PMID- 27687383
TI  - Real-time measurement of blood pressure with Nexfin in a patient with thalidomide
      related phocomelia.
AB  - We report the novel application of photoplethysmographic technology with the
      Nexfin HD monitor for real-time measurement of blood pressure (BP) in a patient
      with tetraamelia. The patient was a 58-year-old man with tetraamelia secondary to
      thalidomide exposure in utero, who presented for surgical excision of a maxillary
      schwannoma. Because difficulty of cuff use on rudimentary limbs and failure to
      gain invasive arterial access due to abnormalities of limb vasculature, this
      population is known to pose some unique challenges for BP measurement. Nexfin may
      offer an alternative noninvasive method to detect BP in patients with phocomelia
      during the perioperative period. 

PMID- 27687384
TI  - Effect of thoracic epidural analgesia on recovery of bowel function after major
      upper abdominal surgery.
AB  - STUDY OBJECTIVE: We investigated whether thoracic epidural analgesia (TEA)
      shortens the first gas-out time compared to intravenous patient-controlled
      analgesia (iv-PCA) and promotes earlier discharge after major upper abdominal
      surgery. DESIGN: Prospective observational study. SETTING: A tertiary care
      university hospital. PATIENTS: Fifty-six patients undergoing major upper
      abdominal surgery. INTERVENTIONS: TEA (n=28) was performed using a paramedian
      approach at T6-7 or T7-8. Hydromorphone (8 MUg/mL) was added to 0.15% ropivacaine
      (bolus/lockout time/basal: 3 mL/15 minutes/5 mL). The iv-PCA regimen (n=28)
      included 20 MUg/mL fentanyl (bolus/lockout time/basal: 0.5 mL/15 minutes/0.5 mL).
      The 2 analgesic methods were maintained for 3 days. MEASUREMENT: The primary end
      point was first gas-out time, and the secondary end points were hospital
      discharge, pain scores, and first voiding time. MAIN RESULTS: No differences in
      first gas-out time (TEA, 4.1+/-1.2 days; iv-PCA, 3.4+/-1.9 days; P=.15) or
      hospital stay (TEA, 9.8+/-2.2 days; iv-PCA, 11.4+/-5.2 days; P=.19) were observed
      between the 2 groups. A visual analog pain scale scores during rest and coughing
      were lower in the TEA than those for iv-PCA even with 40% to 46% less rescue
      analgesic. However, TEA delayed first voiding time (3.6+/-0.9 vs 2.8+/-1.6 days;
      P=.02) and required more frequent bladder catheterization (46% vs 11%; P=.008)
      than those of iv-PCA. CONCLUSION: TEA with a regimen of hydromorphone (8 MUg/mL)
      added to 0.15% ropivacaine did not provide earlier gas-out compared to that of iv
      PCA in patients who underwent major upper abdominal surgery.

PMID- 27687385
TI  - Resuscitation experience in a patient with left ventricular assist device.

PMID- 27687387
TI  - Excess nasopharyngeal secretions in ocular surgery under propofol-based total
      intravenous anesthesia.

PMID- 27687386
TI  - Use of a modified McGRATH MAC and tracheal tube introducer for difficult nasal
      intubation.

PMID- 27687388
TI  - Ultrasound-guided thoracolumbar interfascial plane block: a cadaveric study of
      the spread of injectate.

PMID- 27687389
TI  - Correlation of probability scores of placenta accreta on magnetic resonance
      imaging with hemorrhagic morbidity.
AB  - STUDY OBJECTIVE AND DESIGN: To evaluate the hypothesis that assigning grades to
      magnetic resonance imaging (MRI) findings of suspected placenta accreta will
      correlate with hemorrhagic outcomes. We chose a single-center, retrospective,
      observational design. SETTING, PATIENTS, AND MEASUREMENTS: Nulliparous or
      multiparous women who had antenatal placental MRI performed at a tertiary level
      academic hospital were included. Cases with antenatal placental MRI were included
      and compared with cases without MRI performed. Two radiologists assigned a
      probability score for accreta to each study. Estimated blood loss and transfusion
      requirements were compared among groups by the Kruskal-Wallis H test. RESULTS:
      Thirty-five cases had placental MRI performed. MRI performance was associated
      with higher blood loss compared with the non-MRI group (2600 [1400-4500]mL vs
      900[600-1500]mL, P<.001). There was no difference in estimated blood loss (P=.31)
      or transfusion (P=.57) among the MRI probability groups. CONCLUSIONS: In cases of
      suspected placenta accreta, probability scores for antenatal placental MRI may
      not be associated with increasing degrees of hemorrhage. Continued research is
      warranted to determine the effectiveness of assigning probability scores for
      antenatal accreta imaging studies, combined with clinical indices of suspicion,
      in assisting with antenatal multidisciplinary team planning for operative
      management of this morbid condition.

PMID- 27687390
TI  - Cardiopulmonary exercise testing in a patient with a permanent tracheostomy.
AB  - The benefits of cardiopulmonary exercise testing have been well established.
      Certain patient groups present challenges for conducting such a test. We were
      presented with a patient with a permanent tracheostomy at the preoperative
      assessment clinic. We describe our technique in overcoming the problem of
      connecting him to the testing machine, as this is normally done with the aid of a
      tight-fitting face mask. We used a cuffed tracheostomy tube together with some
      widely available tubing from theaters to connect the patient to the gas analyzer.
      The test was only stopped because of excessive secretions from the patient, and
      we had already established enough data to tell us that the patient was fit enough
      to proceed to surgery. As more patients present with tracheostomies, we feel that
      this case would be a useful reference in managing and assessing such patients. 

PMID- 27687391
TI  - Comparing 3 ventilation modalities by measuring several respiratory parameters
      using the ProSeal laryngeal mask airway in children.
AB  - STUDY OBJECTIVE: To determine quantitative differences in several routinely
      measured ventilation parameters using a standardized anesthetic technique and 3
      different ventilation modalities in pediatric patients with a ProSeal laryngeal
      mask airway (PLMA). DESIGN: Randomized prospective study. SETTING: Pediatric
      hospital of a tertiary care academic medical center. PATIENTS: Thirty-three,
      American Society of Anesthesiologists classification 1-2, pediatric patients (12
      months to 5 years). INTERVENTIONS: Three different ventilation strategies:
      spontaneous ventilation (SV), pressure support ventilation (PSV), and pressure
      controlled ventilation (PCV) were randomly applied to patients who underwent a
      standardized mask induction with sevoflurane/oxygen and propofol 3 mg/kg and
      morphine 0.05 mg/kg administered intravenously followed by PLMA insertion.
      Patients were maintained on sevoflurane and N2O. MEASUREMENTS: We measured the
      differences in end-tidal CO2 (Etco2), tidal volume, and respiratory rate over
      time between SV, PSV, and PCV. These data were recorded at 5-minute intervals.
      MAIN RESULTS: Etco2 (mm Hg) was significantly higher in the SV vs PSV (P=.016)
      and vs PCV (P<.001). Tidal volume (mL/kg) was significantly lower in SV vs PSV
      (P<.001) and vs PCV (P<.001). Respiratory rate (breaths/min) was significantly
      higher in SV vs PSV (P<.001) and vs PCV (P=.005). CONCLUSIONS: All 3 modes of
      ventilation using a PLMA were safely used. Our SV group was noted to have a
      significantly higher Etco2 when compared with PSV and PCV with a mean Etco2 over
      time in excess of 55 mm Hg. PSV and PCV were found to be more appropriate
      ventilation strategies to more optimally control Etco2 over time in these
      patients.

PMID- 27687392
TI  - Inappropriately low bispectral index of the elderly during emergence from
      sevoflurane anesthesia.

PMID- 27687393
TI  - Unexpectedly high incidence of hypothermia before induction of anesthesia in
      elective surgical patients.
AB  - STUDY OBJECTIVE: Perioperative hypothermia is a frequently observed phenomenon of
      general anesthesia and is associated with adverse patient outcome. Recently, a
      significant influence of core temperature before induction of anesthesia has been
      reported. However, there are still little existing data on core temperature
      before induction of anesthesia and no data regarding potential risk factors for
      developing preoperative hypothermia. The purpose of this investigation was to
      estimate the incidence of hypothermia before anesthesia and to determine if
      certain factors predict its incidence. DESIGN/SETTING/PATIENTS: Data from 7
      prospective studies investigating core temperature previously initiated at our
      department were analyzed. Patients undergoing a variety of elective surgical
      procedures were included. INTERVENTIONS/MEASUREMENTS: Core temperature was
      measured before induction of anesthesia with an oral (314 patients), infrared
      tympanic (143 patients), or tympanic contact thermometer (36 patients). Available
      potential predictors included American Society of Anesthesiologists status, sex,
      age, weight, height, body mass index, adipose ratio, and lean body weight.
      Association with preoperative hypothermia was assessed separately for each
      predictor using logistic regression. Independent predictors were identified using
      multivariable logistic regression. MAIN RESULTS: A total of 493 patients were
      included in the study. Hypothermia was found in 105 patients (21.3%; 95%
      confidence interval, 17.8%-25.2%). The median core temperature was 36.3 degrees C
      (25th-75th percentiles, 36.0 degrees C-36.7 degrees C). Two independent factors
      for preoperative hypothermia were identified: male sex and age (>52years).
      CONCLUSIONS: As a consequence of the high incidence of hypothermia before
      anesthesia, measuring core temperature should be mandatory 60 to 120minutes
      before induction to identify and provide adequate treatment to hypothermic
      patients.

PMID- 27687394
TI  - The optimal combination of mechanical ventilator parameters under general
      anesthesia in obese patients undergoing laparoscopic surgery.
AB  - OBJECTIVE: Pulmonary dysfunction after laparoscopic surgery is commonly seen in
      the high-risk group of obese patients. To reduce or avoid this complication
      caused by an improper combination of mechanical ventilation parameters, we
      conducted the following trial of 3 factors with 3 levels of mechanical
      ventilation, aimed to obtain the low airway pressure with good ventilator
      effects. METHODS: Patients were randomly allocated as a sample of cases according
      to the "30<=weight/height(2)<40" obesity index. Anesthesia machine was checked on
      the most fundamental respiratory frequency (f), tidal volume (VT), and
      respiratory ratio (I:E) as the 3 factors of A, B, and C, with 3 levels of f=15,
      12, 9 (beats per minute), VT=8, 10, 12 (mL/kg), and I:E=1:2.5, 1:2.0, 1:1.5. By
      using L9 (3(4)) K=3 repeat, the orthogonal experimental design and analysis table
      for statistics, testing, and analysis of the factors that affect the respiratory
      and change at the end of the level of carbon dioxide (PETCO2), peak airway
      pressure (PIP), mean airway pressure (Pmean), and the end of endogenous airway
      pressure (PEEPi) are of statistical significance. SPSS 13.0 analysis of variance
      was used for statistically significant test, with P<.05 and P<.01 as
      statistically significant differences. RESULTS: In this study, a total of 27
      cases of laparoscopic surgery were allocated in 9 experimental groups under
      general anesthesia. Patients' vital signs are stable; SPO2 is 100%. There are
      different combinations among 3 factors and 3 levels of parameters: (1) the impact
      on the PETCO2, respiratory frequency (f), and/or VT, choose either level, P<.01
      means statistically significant, respiratory ratio (I:E) of either selection,
      P>.05, not statistically significant; (2) the impact of PIP: respiratory
      frequency (f) change, P<.05, significant difference, VT and I:E changes, P<.01
      means statistically significant; (3) the impact of airway pressure on average
      (Pmean): 3 factors and 3 levels of selected respiratory parameters, P<.01 means
      statistically significant. CONCLUSION: The best combination of respiratory
      parameters is A3B1C2, that is, f=9beats per minute, VT=8mL/kg, and I:E=1:2.0.
      That is, neither small tidal volume and faster frequency nor slow frequency large
      tidal volume is a good choice. To let obese patients under general anesthesia can
      obtain a lung protective effect of low airway pressure with good ventilation; it
      is noteworthy that (1) I:E of airway pressure (PIP, Pmean) is the important
      impact factor for the protection of the lung and (2) I:E of airway pressure (PIP,
      Pmean) is the factor with opposite properties.

PMID- 27687395
TI  - Respiratory volume monitoring in an obese surgical population and the prediction
      of postoperative respiratory depression by the STOP-bang OSA risk score.
AB  - STUDY OBJECTIVE: To evaluate use of a respiratory volume monitor (RVM; ExSpiron,
      Respiratory Motion, Inc., Waltham, MA, USA) that provides minute ventilation
      (MV), tidal volume (TV) and respiratory rate (RR) measurements in obese surgical
      patients, hitherto undescribed. DESIGN: Prospective, IRB-approved observational
      study of RVM parameter accuracy in obese surgical patients, designed to test the
      ability of the RVM to detect predefined postoperative respiratory depression
      (PORD) and apneic events (POA) and to correlate STOP-Bang scores with PORD and
      POA. SETTING: Pre-, intra-, and post-op patient-care areas, including the post
      anesthesia care unit (PACU) in 2 academic centers with bariatric populations.
      PATIENTS: 80 patients (47+/-12 years), BMI of 43+/-7 kg/m(2) undergoing elective
      surgery were enrolled. INTERVENTIONS: Data collected included patient
      characteristics, STOP-Bang scores and RVM data from immediately preoperatively
      through PACU completion without effecting standard clinical care. MEASUREMENTS:
      Low minute ventilation (LMV) was defined as 40% of predicted MV, and PORD was
      defined as sustained LMV for 5 minutes. Appropriate parametric and non-parametric
      statistical analyses were performed, P<.05 considered significant. MAIN RESULTS:
      In 56 patients with complete intraoperative ventilator data, correlation between
      RVM and ventilator MV measurements was r=0.89 (measurement bias 1.5%, accuracy
      11%). Measurement error was 0.13 L/min (95% confidence interval-0.93 L/min - 1.20
      L/min). In PACU, 16.3% and 31% of patients had PORD and POA respectively. There
      were no significant differences in the incidence of PORD and POA in 3 STOP-Bang
      risk categories (P>.2). CONCLUSIONS: There was excellent correlation and accuracy
      between the RVM and ventilator volumes in obese surgical patients. A considerable
      number of patients exhibited PORD and POA in the PACU. The STOP-Bang risk scores
      correlated poorly with PORD and POA which suggests that obese surgical patients
      remain at risk for early post-operative respiratory events irrespective of the
      STOP-Bang score.

PMID- 27687396
TI  - Pain as the main presenting symptom in a patient with Elizabethkingia infection.

PMID- 27687397
TI  - Analgesic efficacy of pregabalin in acute postmastectomy pain: placebo controlled
      dose ranging study.
AB  - STUDY OBJECTIVE: We hypothesized that oral administration of a single dose of
      pregabalin 2 hours before modified radical mastectomy (MRM) would produce dose
      related reduction in postoperative opioid consumption. DESIGN: Prospective
      randomized controlled clinical trial. SETTING: Postanesthesia care unit.
      PATIENTS: One hundred twenty adult women scheduled for unilateral (MRM) with
      axillary evacuation. INTERVENTIONS: Patients were randomized to receive either,
      placebo capsule, pregabalin 75 mg, pregabalin 150 mg, or pregabalin 300 mg.
      MEASUREMENTS: The assessment parameters were the postoperative analgesic effect
      using visual analog scale (VAS) pain scores, the subsequent 24-hour morphine
      consumption, and the systemic adverse effects of pregabalin doses. MAIN RESULTS:
      The VAS score at rest and movement was significantly decreased only in group P300
      and group P150 in comparison to group P0 and group P75 at 0 hour (P<.01). The
      median (interquartile range) consumption of morphine in the first postoperative
      24 hours was significantly decreased in group P300 in comparison to group P0 and
      group P75 (P300 vs P0: 6.5 [5-6.5] vs 20.5 [15.8-20.5] [P<.001]; P300 vs P75: 6.5
      [5-6.5] vs 20 [14-20] [P<.001]), but there was no significant difference between
      group P300 and group P150. In addition, there was a significant decrease in
      consumption of morphine in group P150 in comparison to group P0 and group P75
      (P150 vs P0: 7 [5-7] vs 20.5 [15.8-20.5] [P<.001]; P150 vs P75: 7 [5-7] vs 20 [14
      20] [P<.001]). There were statistical significant increase in dizziness and
      blurred vision in group P300 in comparison to other groups (P<.05). CONCLUSIONS:
      A single preoperative oral dose of pregabalin 150 mg is an optimal dose for
      reducing postoperative pain and morphine consumption in patients undergoing MRM.

PMID- 27687398
TI  - Reexpansion pulmonary edema after hepatic hydatid cyst excision.

PMID- 27687399
TI  - Rapid sequence intubation using a videolaryngoscope with a tracheal tube
      introducer in a patient with laryngeal deviation and intractable nasal bleeding.

PMID- 27687400
TI  - Transorbital endotracheal intubation: a nonstandard approach to a difficult
      airway.
AB  - We present the case report of a 49-year-old gentleman with a history of adenoid
      cystic carcinoma of the left nare status post curative bifrontal craniotomy, left
      lateral rhinotomy and medial maxillectomy, adjuvant radiotherapy, and orbital
      exenteration for optic neuropathy, complicated by medial wall dehiscence. His
      course was also complicated by severe radiation trismus, for which he was
      scheduled to undergo bilateral mandibular coronoidectomies. Given his limited
      mouth opening, the surgeon requested a nasal endotracheal tube. Because of
      concerns of traumatizing his nare, we utilized a flexible fiberoptic bronchoscope
      to perform asleep transorbital intubation. Airway management in patients with
      severe trismus may require ingenuity. 

PMID- 27687401
TI  - Pulse oximetry-derived pleth variability index can predict dexmedetomidine
      induced changes in blood pressure in spontaneously breathing patients.
AB  - STUDY OBJECTIVE: Hypertension or hypotension in patients receiving continuous
      infusions of dexmedetomidine (DEX) is often due to changes in vascular resistance
      caused by alpha2 receptor stimulation. We investigated whether baseline perfusion
      index (PI) and pleth variability index (PVI), derived from pulse oximetry
      readings, could predict DEX-induced changes in the hemodynamic status in
      spontaneously breathing patients. DESIGN: Observational study. SETTING: Operating
      room. PATIENTS: Patients (American Society of Anesthesiologists performance
      status 1 or 2) scheduled to undergo lower extremity or abdominal procedures under
      regional anesthesia were approached. INTERVENTIONS: The PI and PVI were set as
      baseline upon arrival in theater and were then measured at 2.5-minute intervals.
      Upon attaining stable hemodynamic status under spontaneous breathing, intravenous
      administration of DEX was initiated at 6 MUg kg(-1) h(-1) for 10minutes, followed
      by continuous infusion at 0.6 MUg kg(-1) h(-1). MEASUREMENTS: Blood pressure,
      heart rate, PI, and PVI were measured. Hypertension was defined as an increase in
      systolic blood pressure (SBP) >15% and hypotension as a decrease in SBP <15% from
      baseline. MAIN RESULTS: Baseline PI and PVI correlated with the degree of change
      in SBP. The maximum percentage increase as well as the maximum percentage of
      decrease in SBP from baseline correlated with baseline PI (r=0.418 [P=.005] and
      r=0.507 [P<.001], respectively) and PVI (r=-0.658 [P<.001] and r=-0.438 [P=.003],
      respectively). PVI <15 identified DEX-induced hypertension (sensitivity 94%,
      specificity 85%) and PVI >16 identified DEX-induced hypotension (sensitivity 83%,
      specificity 64%). CONCLUSIONS: PVI may predict DEX-induced changes in blood
      pressure in spontaneously breathing patients.

PMID- 27687402
TI  - Benign swelling of submandibular glands under general anesthesia "anesthesia
      mumps".

PMID- 27687403
TI  - A comparison of the effectiveness of the streamlined liner of pharyngeal airway
      in paralyzed and nonparalyzed patients undergoing gynecological surgery: a
      randomized trial.
AB  - STUDY OBJECTIVE: To compare the effectiveness of streamlined liner of pharyngeal
      airway (SLIPA) in paralyzed and nonparalyzed, anesthetized patients undergoing
      gynecological surgery. DESIGN: Prospective randomized double-blind clinical
      trial. SETTING: Intraoperative. PATIENTS: A total of 80 female patients with
      American Society of Anesthesiologists class I or II and who were undergoing
      gynecological surgery. INTERVENTIONS: The patients were randomly allocated to
      either the nonparalyzed group (group NR, n=40) or the paralyzed group (group R,
      n=40). MEASUREMENTS: Oropharyngeal leakage pressure was the primary outcome.
      Insertion time; number of insertion attempts; success rate at first insertion;
      involuntary movement; peak inspiratory pressure (PIP); leakage fraction;
      hemodynamic changes; complications, such as blood tinging, regurgitation, and
      sore throat; and recovery time were also evaluated for secondary outcomes. MAIN
      RESULTS: Oropharyngeal leakage pressure, which is primary outcome, was no
      difference among the groups. Insertion time, number of insertion attempts,
      success rate at first insertion, involuntary movement, leakage fraction,
      hemodynamic changes, and complications were not statistically different among the
      groups. The PIP in group NR was significantly increased compared to that of group
      R (P=.002). Recovery time was significantly longer in group R than in group NR
      (P<.001). CONCLUSIONS: SLIPA had good performance in both paralyzed and
      nonparalyzed patients. There was no difference in SLIPA performance or
      complications irrespective of muscle relaxant use, except decrease in PIP and
      prolong recovery time in paralyzed patients.

PMID- 27687404
TI  - Fiberoptic nasopharyngoscopy for evaluating a potentially difficult airway in a
      patient with elevated intracranial pressure.
AB  - A 62-year-old man with a left temporal lobe tumor was scheduled for a semiurgent
      craniotomy for tumor excision. Previously, the patient had a laryngeal carcinoma
      that was resected and treated with chemotherapy and radiotherapy and a history of
      laryngeal biopsy with awake fiberoptic intubation. Because a difficult airway was
      anticipated, awake fiberoptic nasopharyngoscopy of the airway was performed under
      topical anesthesia in the operating room. This revealed a narrow glottic opening
      with no supraglottic pathology or friable tissue. Based on these airway
      observations, we proceeded safely with intravenous induction and secured the
      airway in a controlled fashion, thereby minimizing the risk of increased
      intracranial pressure and catastrophic complications. Nasopharyngoscopy can be
      used safely to evaluate the upper airway to stratify airway management in
      patients with a history of head and neck cancer presenting for neurosurgical
      procedures in the setting of elevated intracranial pressure. 

PMID- 27687405
TI  - Impact of pillow height on double-lumen endotracheal tube intubation with McGRATH
      MAC: a prospective randomized clinical trial.
AB  - STUDY OBJECTIVE: This study aimed to compare the impact of pillow height on
      double-lumen tracheal tube (DLT) intubation with McGRATH MAC (McG) in patients
      undergoing elective surgery. DESIGN: Randomized clinical trial. SETTING:
      Operating room. PATIENTS: Fifty adult patients scheduled for elective surgery
      under 1-lung ventilation with an American Society of Anesthesiologists physical
      status of 1 to 3. INTERVENTIONS: DLT intubation with McG was performed with a
      high pillow (HP group; 25 patients) or low pillow (LP group; 25 patients) by
      anesthesiologists. MEASUREMENTS: Intubation time, number of laryngoscopy, number
      of tracheal intubation attempts to successful intubation, percentage of glottic
      opening score, and subjective difficulty of laryngoscopy and tube passage through
      the glottis were assessed. MAIN RESULTS: Intubation time was significantly
      shorter in the HP group compared with the LP group (HP: 32.1+/-14.9seconds vs LP:
      49.4+/-11.2seconds, P<.001). The number of laryngoscopy were 1 (HP group, 22
      patients; LP group, 17 patients), 2 (HP group, 3 patient; LP group, 7 patients),
      and 3 (HP group, 0 patient; LP group, 1 patient), with no significant difference
      between the 2 groups (P=.197). Although the percentage of glottic opening score
      did not significantly differ between HP and LP groups (HP: 95.6%+/-6.7% vs LP:
      96.0%+/-12.3%, P=.08), the number of tracheal intubation attempts was
      significantly lower in the HP group compared with the LP group (P=.009). The
      visual analog scale score for laryngoscopy did not significantly differ between
      the 2 groups (P=.54). However, the visual analog scale for tube passage through
      the glottis was significantly higher in the LP group than in the HP group
      (P<.001). CONCLUSIONS: Intubation with an HP was associated with a better DLT
      intubation profile than with an LP with McG, possibly due to smoother tracheal
      tube progression through the glottis.

PMID- 27687406
TI  - Anesthetic considerations for renal transplant surgery in patients with
      mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      syndrome: a case report.
AB  - Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      syndrome is a progressive syndrome with variable involvement of multiple-organ
      systems. These patients require special consideration for preoperative
      optimization, intraoperative management, and postoperative care. The medical
      literature regarding perioperative management of these patients relies heavily on
      case reports. Here we present a novel experience providing care for a patient
      with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like
      episodes syndrome who underwent renal transplantation for focal segmental
      glomerulosclerosis and end-stage renal disease. 

PMID- 27687407
TI  - Clinical experiences of ultrasound-guided subpectoral interfascial plane block.

PMID- 27687408
TI  - Anesthesia management in the coexistence of myasthenia gravis and parkinsonism.

PMID- 27687409
TI  - Evaluating sepsis training for medical students and nonphysicians in Malawi.
AB  - STUDY OBJECTIVE: This study aimed to evaluate whether (regarding the Surviving
      Sepsis Campaign [SSC] guidelines) the training of Malawis scarce medical staff is
      adequate. Hospitals in Malawi have a severe shortage of human resources and
      therefore rely heavily on junior staff. Sepsis is a leading cause of admission to
      hospitals particularly in resource poor countries. It is associated with a high
      mortality rate. The SSC guidelines have been developed to help frontline staff
      diagnose and treat patients with sepsis. DESIGN: A questionnaire consisting of 10
      multiple choice questions, which was to be completed before and after a teaching
      module. SETTING: Anesthesia courses at the University of Malawi. INTERVENTION:
      Participants had to answer the questionnaire before and after their teaching
      block on anesthetics and critical care. The medical students have a 2-week
      teaching block, and the nonmedical staff have an intensive 3-day training course.
      MBBS 1 was asked only once as a baseline. PARTICIPANTS: 168 medical students and
      31 nonphysician staff returned 345 questionnaires (return rate, 97.1%).
      MEASUREMENTS: A total of 345 anonymous multiple choice questionnaires were
      completed. The same questionnaire was then repeated after their teaching block on
      anesthesia and critical care (not MBBS 1). The aim was for us to assess the
      knowledge the students had of sepsis. Overall 67% of the questions were answered
      correctly (2299 correct answers of 3450). The MBBS IV students had an average
      score of 68% to 72%, and the MBBS I students had a score of 42%. The highest
      score was achieved by the nonphysician clinical staff after their teaching as
      they improved by 11% (65%-76%). CONCLUSIONS: Medical students and health care
      workers have a lack of knowledge regarding the SSC guidelines which needs to be
      addressed via training. The medical student teaching was not as effective as the
      nonphysician clinical staff course, and therefore, we need to think about
      restructuring their teaching block by having an intensive "Sepsis Day" that
      focuses on the SSC guidelines.

PMID- 27687410
TI  - Intraocular pressure changes: the McGrath video laryngoscope vs the Macintosh
      laryngoscope; a randomized trial.
AB  - STUDY OBJECTIVE: To determine the effects of the McGrath Series 5 video
      laryngoscope on intraocular pressure (IOP) during laryngoscopy. DESIGN:
      Prospective, randomized, double blind. SETTING: Operating room. PATIENTS: Eighty
      adult patients of American Society of Anesthesiologist physical status 1
      scheduled for nonophthalmic elective surgery under general anesthesia.
      INTERVENTIONS: The endotracheal intubation was provided using McGrath series 5
      video laryngoscope in MG group (n=40) or Macintosh laryngoscope in M group
      (n=40). MEASUREMENTS: The IOP of the right and left eyes was measured before and
      after the laryngoscopic process. MAIN RESULTS: The mean arterial blood pressure
      values just before laryngoscopy and intubation and after intubation were 77.38+/
      6.18 and 97.38+/-12.77 in the McGrath video laryngoscope group and 75.85+/-7.88
      and 99.12+/-14.30 in the Macintosh laryngoscope group, respectively. The IOP
      values of the left eye after intubation and at the 5th and the 10th minutes in
      the Macintosh laryngoscope group were found to be significantly higher than those
      in the McGrath video laryngoscope group (P=.019, P=.019, and P=.007,
      respectively). In addition, the IOP values of the right eye were found to be
      higher after intubation and at the 5th and the 10th minutes in the Macintosh
      laryngoscope group, compared to the McGrath video laryngoscope group (P=.009,
      P=.021, and P=.011, respectively). The mean IOP values for the left eye just
      before laryngoscopy and intubation and after intubation were 10.65+/-2.52 and
      15.57+/-3.62 in the McGrath video laryngoscope group, and for the right eye, they
      were 10.60+/-1.64 and 17.17+/-2.38 in the Macintosh laryngoscope group,
      respectively. CONCLUSION: The McGrath Series 5 video laryngoscope may provide a
      lower IOP level compared to the Macintosh laryngoscope in an otherwise healthy,
      young patient population.

PMID- 27687411
TI  - The importance of maintaining an optimal hemodynamic state during minimally
      invasive fetal surgery.

PMID- 27687412
TI  - Insomnia may increase anesthetic requirement.

PMID- 27687413
TI  - Efficacy of the Pentax-AWS Airwayscope with a newly developed Intlock for a
      double-lumen tracheal tube.

PMID- 27687414
TI  - Emergency surgery for RhD-negative patients in the Asia region.

PMID- 27687415
TI  - The glycemic response to insulin as extracted from the DeLiT trial is not an
      indicator of tissue insulin sensitivity.

PMID- 27687416
TI  - Intravenous line establishment and anesthesia induction in an upper extremity
      with congenital arteriovenous malformation.

PMID- 27687417
TI  - Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic
      surgeries: a double-blind randomized controlled trial.
AB  - STUDY OBJECTIVE: The aim of this study is to compare the analgesic effect of
      intravenous infusion of magnesium sulfate to ketorolac during laparoscopic
      surgeries. DESIGN: Double-blind randomized controlled trial. SETTING: University
      affiliated teaching hospital. PATIENTS: Sixty women submitted to laparoscopic
      gynecologic oncology surgeries. INTERVENTIONS: Intravenous ketorolac 30 mg in
      bolus followed by saline infusion (group K), intravenous magnesium sulfate 20
      mg/kg in bolus followed by magnesium 2 mg kg(-1) h(-1) (group M) or intravenous
      saline solution 20 mL in bolus followed by saline infusion during the entire
      procedure (group S). MEASUREMENTS: Postoperative pain, nausea, vomiting,
      sedation, opioid consumption, time to first dose of analgesic. MAIN RESULTS:
      Magnesium sulfate reduced opioid consumption compared with placebo in the
      postoperative, but not in the intraoperative, period. Nausea, not vomiting, was
      reduced in ketorolac but not in the magnesium group. Pain intensity was higher in
      placebo than in the other 2 groups during all periods of observation. In the
      first 60 minutes, pain intensity was lower in the magnesium than in the ketorolac
      or the placebo group. CONCLUSION: Intraoperative magnesium sulfate improves
      postoperative pain control, acting as an opioid-sparing adjuvant, and is similar
      to ketorolac 30 mg administered in the beginning of surgery.

PMID- 27687418
TI  - Perioperative course in patients with hereditary or acquired angioedema.
AB  - PURPOSE: Two types of bradykinin-mediated angioedema, hereditary angioedema (HAE)
      and acquired angioedema (AAE), result from deficiency or dysfunction of C1
      esterase inhibitor, leading to an overproduction of bradykinin, which can lead to
      vascular permeability and life-threatening angioedema of the airway. The
      objective of this study was to review perioperative outcomes in a series of
      patients with HAE and AAE and to review current knowledge about anesthetic
      complications in patients with HAE or AAE. METHODS: Medical records were
      retrospectively reviewed for perioperative complications in patients with HAE or
      AAE who underwent general anesthesia from January 1, 2000, to December 31, 2014,
      at our institution. RESULTS: Twenty-four patients (13 with HAE, 10 with AAE, and
      1 with unspecified angioedema) underwent 38 instances of general anesthesia with
      airway manipulation. All except 4 received prophylactic therapy. One patient, a
      67-year-old woman who was pretreated with stanozolol and fresh frozen plasma
      required reintubation after postoperative airway edema developed. CONCLUSION:
      Life-threatening episodes of angioedema of the airway occur infrequently, but
      they can occur in patients who received pretreatment and in patients who have
      previously undergone anesthesia uneventfully. Anesthesiologists must be ready to
      emergently manage a difficult airway and must be familiar with recommendations
      provided in consensus guidelines for the treatment of HAE and AAE patients.

PMID- 27687419
TI  - Myoclonus-like involuntary movements following cesarean delivery epidural
      anesthesia.
AB  - Spinal myoclonus following neuraxial anesthesia is rare. This report describes a
      case of myoclonus-like involuntary movement that occurred during the recovery
      from epidural anesthesia for a cesarean delivery. The patient's symptom improved
      with the administration of benzodiazepine, and the patient recovered with no
      neurological sequelae. In conclusion, epidural anesthesia can cause spinal
      myoclonus, which can be treated with a benzodiazepine. 

PMID- 27687420
TI  - Surgical Apgar score is associated with myocardial injury after noncardiac
      surgery.
AB  - STUDY OBJECTIVE: To assess the impact of intraoperative hemodynamics in the
      development of perioperative myocardial infarction (MI) and myocardial ischemia
      after noncardiac surgery. DESIGN: Single-center retrospective cohort study of
      surgical patients from 2007 to 2012. SETTING: Postanesthesia care unit, intensive
      care unit, and medical-surgical ward at an academic tertiary medical center.
      PATIENTS: A total of 46,799 adult noncardiac, nonthoracic surgery patients, for
      which 2290 peak cardiac troponin (cTn) levels were available. MEASUREMENTS: The
      10-point Surgical Apgar Score (SAS) was calculated from intraoperative heart
      rate, blood pressure, and blood loss. Peak troponin (cTn) levels, hospital length
      of stay, 7- and 30-day postoperative mortality, patient demographics, and prior
      medical conditions were gathered. Troponin leak was defined as cTn-I 0.6 to 1.5
      ng/mL or cTn-T 0.1 to 0.3 ng/mL; perioperative MI criteria were cTn-I greater
      than 1.5 ng/mL or cTn-T greater than 0.30 ng/mL. MAIN RESULTS: Of 46,799
      noncardiac surgical cases, 209 (0.4%) and 192 (0.4%) suffered cTn leak and MI,
      respectively. Low SAS (0-4) was associated with increased risk of cTn leak and
      perioperative MI (univariate odds ratio, 2.76 and 2.06; 95% confidence interval,
      2.20-3.45 and 1.57-2.70, respectively). In multivariable analysis, Surgical Apgar
      Score, age 65 years or older, American Society of Anesthesiologists physical
      status greater than or equal to III, emergency surgery, history of MI or
      hypertension, prolonged intraoperative tachycardia (heart rate >100 beats/min for
      >59 minutes), and prolonged hypotension (mean arterial pressure <40 mm Hg for >2
      minutes) were independently associated with cTn leak and perioperative MI.
      CONCLUSIONS: Low SAS scores (0-4) may be associated with cTn elevation after
      noncardiac surgery. SAS-based risk stratification may guide perioperative cTn
      surveillance in lieu of routine postoperative screening.

PMID- 27687421
TI  - The novel use of different bupivacaine preparations with combined regional
      techniques for postoperative pain management in non-opioid-based laparoscopic
      inguinal herniorrhaphy.
AB  - Opioids are important for surgical pain control but may not be appropriate for
      patients with narcotic abuse histories or opioid intolerance. We describe a
      laparoscopic bilateral inguinal herniorrhaphy performed without perioperative or
      postoperative narcotics. Postoperative analgesia involves a novel technique using
      2 different bupivacaine formulations that act synergistically to avoid lag time
      and provide extended pain relief during the acute surgical recovery phase. 

PMID- 27687422
TI  - In vitro antimicrobial activity of commonly used vasoactive drugs.
AB  - STUDY OBJECTIVE: Microbial contamination during preparation of the infusion drugs
      is an important issue in intensive care units. Objective of this study was to
      investigate in vitro antimicrobial properties of commonly used vasoactive drugs.
      DESIGN: Prospective study. SETTING: Clinical microbiology laboratory of a
      university hospital. MEASUREMENTS: Growth of the microorganisms Staphylococcus
      aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and
      Candida albicans in saline dilutions of adrenaline at 1, 10, and 100 MUg/mL;
      noradrenaline at 1, 10, and 100 MUg/mL; and dopamine at 0.1, 1, and 10 mg/mL
      concentrations was investigated. Each drug solution and saline were analyzed with
      a digital pH meter. MAIN RESULTS: Saline dilutions of adrenaline, noradrenaline,
      and dopamine at clinically used concentrations decreased microbial growth. The
      highest concentration doses of adrenaline, noradrenaline, and dopamine used in
      the study had significant antimicrobial effect when compared to the low and
      moderate doses. This effect was shown with the all microorganisms. S aureus, S
      epidermidis, and C albicans were more sensitive; on the other hand, E coli and P
      aeruginosa were more resistant against the effect of the drug dilutions.
      CONCLUSIONS: To limit microbial growth in case of contamination of the drug
      solution, it is advisable to use more concentrated dilutions of adrenaline,
      noradrenaline, and dopamine used in clinical practice.

PMID- 27687423
TI  - Gum elastic bougie-guided insertion of laryngeal tube suction-II in patients with
      difficult airway.

PMID- 27687424
TI  - Reinforcing of the blocker tube of air-Q blocker device.

PMID- 27687425
TI  - Using an at-risk salary model to improve throughput in academic medical center
      operating rooms.
AB  - STUDY OBJECTIVE: The objective was to analyze if an at-risk salary model for
      faculty anesthesiologists could improve on-time first case starts (FCSs) and case
      turnovers (TOs) in an academic hospital inpatient operating room (IOR) and
      ambulatory surgery center (ASC). Organizational goals were 65% and 70% on-time
      FCS and case TO times for IOR and ASC, respectively. DESIGN: This was a
      retrospective study. SETTING: Surgical cases performed at both the IORs and the
      ASCs at a large academic medical center were included. INTERVENTIONS: We
      converted 5% to 7% (academic rank dependent) of anesthesiologist salary from
      guaranteed to an at-risk salary model. Salary was earned back on a case-by-case
      basis by starting cases on time or by documenting a valid reason for case delay
      in the anesthesia record. On-time first case and goal TO times were determined
      using American Association of Clinical Directors standard definitions.
      MEASUREMENTS: Data were reviewed for 1 year prior to implementation of the at
      risk salary model and for 1 year after the implementation. Monthly average on
      time FCS and TO times were compared between the preimplementation and
      postimplementation time frames. Data were analyzed using analysis of variance for
      repeated measures. MAIN RESULTS: After the implementation of the at-risk salary
      model, the organization experienced a 33% and 86% improvement in on-time FCSs (P<
      .01) in the inpatient and ambulatory operating rooms, respectively. A 41% (IOR)
      and 44% (ASC) improvement in timely case TOs (P< .01) was also seen. CONCLUSIONS:
      Anesthesiologists can drive efficiency in an operating room setting. By
      incentivizing on-time FCS and timely case TO with an at-risk salary model for
      faculty anesthesiologists, we were able to demonstrate a sustained significant
      improvement for these metrics. In both an inpatient and an ambulatory setting,
      operating room efficiency may be best served by aligning provider financial
      incentives with desired outcome metrics.

PMID- 27687426
TI  - Noninvasive ventilation during spontaneous breathing anesthesia: an observational
      study using electrical impedance tomography.
AB  - STUDY OBJECTIVE: To assess the effects of noninvasive ventilation (NIV) during
      spontaneous breathing anesthesia on functional residual capacity and ventilation
      distribution. DESIGN: Prospective and observational study. SETTING: Operating
      room, military teaching hospital. PATIENTS: Eighteen adult patients submitted to
      digestive endoscopic procedures under spontaneous breathing anesthesia.
      INTERVENTIONS: Anesthetic management was standardized. Patients were submitted to
      combined digestive endoscopic procedures (gastric fibroscopy and colonoscopy)
      under spontaneous breathing anesthesia in lateral decubitus position. Anesthesia
      was induced with propofol intravenous 1 mg/kg. Repeated boluses of propofol were
      administered according to the patients' clinical needs during endoscopic
      procedures. Ventilation distribution and functional residual capacity were
      assessed by electrical impedance tomography. MEASUREMENTS: Ventilation
      distribution was assessed by electrical impedance changes in left and right lung,
      and functional residual capacity changes were evaluated by measurement of end
      expiratory lung impedance changes. Measures were performed before anesthesia
      induction, 5 minutes after anesthesia induction during gastric fibroscopy, at the
      end of gastric fibroscopy, 5 minutes after NIV application during colonoscopy,
      and at the end of colonoscopy. MAIN RESULTS: In awake patients, tidal volume was
      primarily distributed to the dependent lung (57.5% vs 43.1%; P=.009). After
      anesthesia induction, we observed a shift of ventilation to the nondependent lung
      (43.1% before anesthesia, 58.9% after anesthesia; P=.002) and marked decrease in
      end-expiratory lung impedancemetry of -1.68UI (4.47). Noninvasive ventilation
      application resulted in a significant increase of end-expiratory lung
      impedancemetry of 1.33 (6.49) (P=.005) but did not impact ventilation
      distribution. CONCLUSIONS: This study showed that NIV application in pressure
      support mode during spontaneous breathing anesthesia increased functional
      residual capacity. Other studies are needed to evaluate the clinical impact of
      this technique during anesthesia, especially in patients with poor respiratory
      conditions.

PMID- 27687427
TI  - The effect of serratus plane block performed under direct vision on postoperative
      pain in breast surgery.
AB  - STUDY OBJECTIVES: To determine the effectiveness of serratus plane block
      performed under direct vision on postoperative pain after mastectomy. DESIGN: We
      performed a retrospective study of elective breast surgery patients undergoing
      mastectomy over 6 months. We collected data on the outcomes for the pain score
      and use of analgesia in recovery, the use of analgesia and antiemetics overnight,
      and the pain score and mobilization status of the patient 1 day after the
      operation. SETTING: Breast cancer is the most common cancer in women, and
      mastectomy is commonly performed as part of the management. A mastectomy can
      cause significant acute pain which progresses to chronic pain in 25% to 60% of
      women. Recent studies have suggested that a serratus plane block is a viable
      alternative to regional anesthetic techniques without the side effect profile and
      that injection of local anesthetic into serratus anterior provided predictable
      and effective anesthesia to the chest wall. Serratus blocks target the thoracic
      nerves more selectively than pectoral blocks, and local blocks can reduce the use
      of opiates postoperatively thereby lessening opiate-related side effects.
      PATIENTS: Our sample included 16 patients who had received a serratus block and
      11 patients who only had wound infiltration with levobupivacaine with adrenaline
      and clonidine. INTERVENTION: Serratus plane block was conducted by injecting 50%
      of the totally available levobupivacaine 0.375% with adrenaline and clonidine
      deep to serratus anterior under direct observation. MAIN RESULTS: No patients
      receiving a serratus block suffered severe pain in recovery or day 1
      postoperatively. Patients receiving wound infiltration alone had 2 patients
      suffering severe pain in recovery and 3 patients suffering severe pain day 1
      postoperatively. CONCLUSION: Serratus block provides effective regional
      anesthesia, suitable for mastectomies, and currently appears to be superior to
      wound infiltration alone. However, further data will need to be collected to
      support this finding.

PMID- 27687428
TI  - Bilateral tension pneumothorax during colonoscopy in a patient with chronic
      obstructive pulmonary disease: a case report.
AB  - Colonoscopy is widely performed for the diagnosis and treatment of various
      colonic disorders and the screening and surveillance of colorectal neoplasia.
      According to research evidence, up to one-third of patients had at least 1 minor
      and transient gastrointestinal symptom after colonoscopy. Although severe
      complications developed uncommonly, they are potentially serious and life
      threatening. Here, we present the case of a 95-year-old man with chronic
      obstructive pulmonary disease who developed bilateral tension pneumothorax during
      therapeutic colonoscopy for sigmoid volvulus. In this case, air trapping
      resulting from the Valsalva maneuver under inadequate pain control may be the
      mechanism for fatal tension pneumothorax during colonoscopy. 

PMID- 27687430
TI  - Erratum to 'the "hoop loop" device increases anesthesia and positioning safety in
      the magnetic resonance imaging (MRI) scanner' Journal of Clinical Anesthesia
      2010:22(7):574-5.

PMID- 27687429
TI  - Hyperlipidemia sink for anesthetic agents.
AB  - We present a case that involves anesthetic resistance during anesthesia for
      electroconvulsive therapy. Despite adequate dosing of both intravenous and
      inhalation anesthetics, our patient was resistant to induction of the state of
      general anesthesia. Subsequently, we noticed extreme hyperlipidemia. We
      hypothesized that the patient's extreme hyperlipidemia served as an anesthetic
      "sink" and prevented the full dose of intravenous agents from quickly reaching
      their intended site of action. 

PMID- 27687431
TI  - Different interventions in preventing opioid-induced cough: a meta-analysis.
AB  - BACKGROUND: Cough is one of the most common complications of opioids. Many
      studies have evaluated the effect of various drugs in preventing opioid-induced
      cough (OIC). However, there is existing controversy about those reports. The
      present study was performed to assess the efficacy of different interventions on
      OIC. METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), PubMed, and Embase to identify randomized controlled trials on the
      efficacy of different drugs in the prevention of OIC. Opioids included fentanyl,
      sufentanil, and remifentanil. We mainly investigated the incidence and severity
      of OIC after different interventions. RESULTS: Thirty-four trials including 9906
      patients were analyzed in this study. Twenty different drugs were reported, and
      10 drugs were indentified in more than 2 articles. These drugs, including
      lidocaine, ketamine, dexmedetomidine, priming of fentanyl, propofol, dezocine,
      dexamethasone, dextromethorphan, and magnesium sulfate (MgSO4), showed a
      significant efficacy compared with controls. There were insufficient numbers of
      trials for salbutamol, clonidine, tramadol, pentazocine, rocuronium, midazolam,
      atropine, terbutaline, sodium chromoglycate, beclomethasone, and ephedrine. From
      these data, we found that salbutamol, tramadol, midazolam, and atropine were
      ineffective. CONCLUSIONS: This meta-analysis suggested that the prophylactic
      administration of lidocaine, ketamine, dexmedetomidine, priming of fentanyl,
      propofol, and dezocine was effective in preventing OIC.

PMID- 27687432
TI  - The peri-operative management of a cesarean section in a patient with Goldenhar
      syndrome (GS): A case report.

PMID- 27687433
TI  - Individualized remediation during fellowship training.
AB  - The Accreditation Council for Graduate Medical Education requires medical
      training programs to monitor, track, and formally document a fellow's
      performance. If deficiencies are found, programs are expected to prepare and
      implement an effective plan of action for improvement and to ensure that
      graduates acquire the personal and professional attributes of an independent
      physician. We revised our evaluation policy and instituted a remediation protocol
      in 2008. Since that time, 130 pediatric anesthesia fellows have graduated. Seven
      fellows (5%) underwent departmental formal consultation for deficient behavior or
      poor performance. Of these 7 fellows, 4 underwent an individualized remediation
      program (IRP). A formal performance review and written contract, with
      specifically identified problems and general themes, recommendations for time
      based successful behaviors, and clearly identified consequences for unsuccessful
      behaviors, was initiated for each fellow undergoing an IRP. All fellows who
      participated in this program completed their subspecialty training in pediatric
      anesthesia, and all eligible fellows have successfully achieved their
      subspecialty board certification. Our approach has the advantage of
      multimodality, time-based daily evaluations, and group discussions in the context
      of a Clinical Competency Committee. Utilization of an IRP as a metric for
      progress has features similar to effective cognitive behavioral therapy contracts
      and has ensured that our graduates are held to clearly delineated and specified
      skills and behaviors that allow them to work independently in the field of
      pediatric anesthesiology. 

PMID- 27687434
TI  - Efficacy of palonosetron in postoperative nausea and vomiting (PONV)-a meta
      analysis.
AB  - INTRODUCTION: Palonosetron is a second-generation 5-HT3 receptor antagonist with
      proposed higher efficacy and sustained action for prophylaxis of postoperative
      nausea and vomiting (PONV). METHODS: Randomized controlled trials involving adult
      population undergoing elective surgery under general anesthesia comparing
      palonosetron to placebo, ramosetron, granisetron, and ondansetron were included.
      Data were extracted for vomiting incidence (VI), complete response (no
      nausea/vomiting; Complete Response [CR]), and rescue antiemetic need. This was
      categorized as early phase (24 hours postoperative for ramosetron and 6 hours for
      rest) and delayed phase (48 hours for ramosetron and 24 hours for rest). VI and
      CR were used as markers of drug efficacy. Any adverse effects were evaluated.
      RESULTS: Twenty-two trials (4 with 3 groups) were included (comparing
      palonosetron to placebo in 5, ramosetron in 5, granisetron in 4, and ondansetron
      in 12 subgroups). Palonosetron demonstrated statistical superiority over placebo
      for VI and CR, both early/delayed PONV prevention. For delayed phase,
      palonosetron surpassed ramosetron in all 3 variables; however, none of the
      variables attained statistical significance during early phase. In early phase,
      palonosetron had better VI and CR than did granisetron; however, variables other
      than CR (better for palonosetron) failed to achieve statistical significance for
      delayed phase. All 3 outcomes were significantly better for palonosetron compared
      with ondansetron in delayed phase, but statistical superiority could only be
      demonstrated for VI in early phase. Being inconsistently documented across
      trials, nausea scores could not be evaluated. CONCLUSION: Palonosetron is as safe
      as and more effective than placebo, ramosetron, granisetron, and ondansetron in
      preventing delayed PONV. For early PONV, it has higher efficacy over placebo,
      granisetron, and ondansetron.

PMID- 27687435
TI  - King Vision video laryngoscope versus Lightwand as an intubating device in adult
      patients with Mallampatti grade III and IV patients.
AB  - STUDY OBJECTIVE: Anticipated and unanticipated difficult airways are often
      encountered by anesthesiologists in their clinical practice. There are various
      devices available in such situations. We aim to compare King Vision video
      laryngoscope and Lightwand for their performance as an intubating device in
      predicted difficult intubation. DESIGN: Prospective, randomized, single blind
      study. SETTING: Jawaharlal Nehru Medical College. PATIENTS: Sixty ASA 1 and 2
      with Mallampati grade III and IV. INTERVENTIONS: Patients were divided into 2
      groups of 30 patients each. Patients of King Vision group [n=30] and Lightwand
      group [n=30] were intubated using respective devices. Primary outcome measure was
      time taken to intubate whereas secondary outcome measure ware number of attempts
      for intubation, no of adjustment maneuvers, changes in heart rate and mean
      arterial pressure and airway trauma. MEASUREMENTS AND MAIN RESULTS: Mean
      intubation time using King Vision video laryngoscope (19.50+/-6.73 seconds was
      lower than the intubation time using Lightwand 25.40+/-7.42 s, P=.00). The
      difference between number of attempts, success of intubation, numbers of
      adjustment maneuvers were comparable. There was a significant rise in heart rate
      within the groups from the pre-induction values. However inter group variations
      were similar. In addition, there was a significant rise in mean arterial pressure
      within the groups from the pre-induction values. Inter group variations show less
      increase in mean arterial pressure with Lightwand at immediate post intubation
      (P=.0234) and at 3 min and 5 min post intubation anesthesia.

PMID- 27687436
TI  - Ultrasound-guided high-thoracic paravertebral block relieves referred pain caused
      by cervical spondylosis and provides stellate ganglion-blocking effect.

PMID- 27687437
TI  - Intraoperative cardiovascular collapse in a patient with epidermolysis bullosa.

PMID- 27687438
TI  - A survey of patients' understanding and expectations of persistent postsurgical
      pain in a preoperative testing center.
AB  - STUDY OBJECTIVE: Acute postoperative pain may transition to persistent/chronic
      pain in up to 50% or more of patients after certain surgeries. Despite this
      concern, it is unclear that patients' preprocedure understanding and expectations
      are aligned with these potential outcomes. This study was designed to evaluate
      the extent of this alignment and the potential impact on the quality of
      risk/benefit discussions before procedures. DESIGN: Prospective survey. SETTING:
      A large, tertiary care preoperative assessment clinic. PATIENTS: A total of 1481
      adult patients. INTERVENTIONS: Survey administration. MEASUREMENTS: The survey
      items evaluated patients' expectations of postoperative pain and how familiar
      patients were with the risk of persistent postsurgical pain based on their
      specific characteristics and procedure type. MAIN RESULTS: The overwhelming
      majority (80%) of patients were unaware of the risk of persistent postsurgical
      pain. Given the choice, most patients (65%) wanted to be informed of their risk,
      and 25% stated that it might even affect their decision to proceed with surgery.
      CONCLUSIONS: There is great need for health care providers to discuss the
      significant risk of persistent postsurgical pain with patients in the
      preoperative setting. Patients need to be armed with realistic data to ensure
      high-quality discussions of risk/benefit, align expectations with outcomes, and
      potentially identify high-risk groups in which preoperative intervention can
      reduce the likelihood or severity of persistent postoperative pain syndromes.

PMID- 27687439
TI  - "Are We hurting ourselves?" What is the prevalence of back pain in anesthesia
      providers?
AB  - STUDY OBJECTIVE: Back injuries are a highly reported category of occupational
      injury in the health care setting. The daily clinical activities of an anesthesia
      provider, including lifting, pushing stretchers, transferring patients, and
      bending for procedures, are risk factors for developing low back pain. The
      purpose of this study is to investigate the prevalence of work related low back
      pain in anesthesia providers. DESIGN/SETTING: We conducted a cross-sectional
      survey study of anesthesia providers at an academic institution. PATIENTS: The
      target population included all 141 clinical anesthesia providers employed by the
      Penn State Milton S. Hershey Medical Center Department of Anesthesia.
      INTERVENTIONS: A survey study was conducted using the Oswestry Disability Index
      (ODI), a validated scoring system for low back pain. Additional questions related
      to the daily activities of clinical anesthesia practice were also asked. The
      survey instrument underwent pretesting and clinical sensibility testing to ensure
      validity and consistent interpretation. MEASUREMENTS: The primary self-reported
      measures were the prevalence of low back pain in anesthesia providers and an
      assessment of disability based on the ODI. Secondary functional measures included
      the impact of low back pain on work flow. MAIN RESULTS: Nearly half (46.6%) of
      respondents suffer from low back pain attributed to clinical practice. In this
      subset of respondents, 70.1% reported not having back pain prior to their
      anesthesia training. Of those with low back pain, 44% alter their work flow, and
      9.8% reported missing at least one day of work. Six providers (5.3%) required
      surgical intervention. Using the ODI score interpretation guidelines, 46% of
      respondents had a "mild disability" and 2% had a "moderate disability."
      Respondents reporting feeling "burned out" from their job had a significantly
      higher average ODI score compared to those who did not (6.8 vs 3.3, respectively;
      P=.01). CONCLUSIONS: Nearly half of all anesthesia providers sampled suffer from
      low back pain subjectively attributed to their clinical practice. This leads to
      changes in work flow and missed days of work. The results of this study suggest a
      deficiency in the effectiveness of anesthesia training programs in teaching
      proper techniques to prevent musculoskeletal injuries.

PMID- 27687440
TI  - Sevoflurane-induced arrhythmia in healthy adult.
AB  - Inhalatory anesthetic agents are frequently used for anesthesia maintenance.
      Sevoflurane is considered one of the safest regarding its cardiac effects. We
      report a case of a cardiac arrhythmia induced by sevoflurane in an otherwise
      healthy adult and discuss sevoflurane's cardiac effects. 

PMID- 27687442
TI  - Bilateral pneumonectomy with difficult airway managed by using a combination of i
      gel and EZ-Blocker.

PMID- 27687441
TI  - Impact of time interval between remifentanil and propofol on propofol injection
      pain.
AB  - STUDY OBJECTIVE: To determine the most effective time interval between
      remifentanil and propofol (TimeRP) for the prevention of propofol injection pain
      in association with remifentanil dosage. DESIGN: Prospective randomized study.
      SETTING: Operating room of a university hospital. PATIENTS: Sixty American
      Society of Anesthesiologists physical status 1 and 2 patients scheduled for
      elective surgery under general anesthesia. INTERVENTIONS: Patients were randomly
      assigned to 1 of 3 groups to receive remifentanil at dosages of 0.25, 0.5, or
      0.75 MUg/kg over 30 seconds before the injection of 1% propofol 2 mg/kg. TimeRP
      was defined as the time interval from the initiation of the remifentanil
      injection to the initiation of the propofol injection. TimeRP for each subsequent
      patient was determined by the response of the previous patient using an up-and
      down sequential allocation method. Injection pain caused by propofol was
      evaluated using a 4-point scale during the propofol injection. MEASUREMENTS:
      TimeRP50 was defined as the TimeRP at which propofol injection pain was absent in
      50% of patients, and it was estimated using isotonic regression for each dose
      group. MAIN RESULTS: TimeRP50 was significantly lower in the remifentanil 0.75
      MUg/kg group (38.6 seconds, 83% confidence interval [CI], 35.6-45.0) than in the
      0.5 MUg/kg group (65.0 seconds; 83% CI, 52.5-75.0) or the 0.25 MUg/kg group (66.6
      seconds; 83% CI, 57.1-76.5). CONCLUSIONS: The efficacy of remifentanil
      pretreatment for preventing propofol injection pain can be influenced by the time
      interval between remifentanil and propofol as well as the remifentanil dose.

PMID- 27687443
TI  - Study citation irrespective of retraction status.

PMID- 27687444
TI  - Acute exacerbation of idiopathic pulmonary fibrosis after total hip replacement.

PMID- 27687445
TI  - Incidence of acute kidney injury after elective lower limb arthroplasty.
AB  - STUDY OBJECTIVE: The aim of this study was to establish the incidence of acute
      kidney injury (AKI) in patients undergoing elective hip and knee arthroplasty.
      DESIGN: This was a retrospective cohort study. SETTING: The study was conducted
      in a district general hospital in the United Kingdom. PATIENTS: All patients
      undergoing elective hip and knee arthroplasty over a period of 6 months were
      included in the study. MEASUREMENT: Preoperative and postoperative serum
      creatinine concentration was recorded in all patients. AKI was defined according
      to the Acute Kidney Injury Network classification as an increase of serum
      creatinine concentration of >26.5 MUmol/L (>=0.3 mg/dL) or increase to 1.5-fold
      from baseline. MAIN RESULTS: Three hundred thirty-seven patients were included in
      the study. Forty-eight had preexisting stage 3 chronic kidney disease (CKD). The
      overall incidence of AKI in our study was 6.2%. The incidence in patients with
      preexisting stage 3 CKD (estimated glomerular filtration rate <60 mL/[min 1.73
      m(2)]) was 16.3%, whereas in patients without preexisting stage 3 CKD, the
      incidence was 4.5%. CONCLUSION: We identified stage 3 or higher CKD as a major
      risk factor for developing postoperative AKI. Preexisting CKD raised the risk of
      developing AKI 4-fold. We recommend that all patients undergoing lower limb
      arthroplasty should have renal function assessed preoperatively. In the
      perioperative period, renal function should be monitored in all patients. This is
      of particular importance in patients with estimated glomerular filtration rate
      <60.

PMID- 27687446
TI  - Interaction between magnesium sulfate and neuromuscular blockers during the
      perioperative period. A systematic review and meta-analysis.

PMID- 27687447
TI  - The risk factors of intraoperative anesthesia adverse events in children with
      laryngeal diseases.
AB  - BACKGROUND: This study aimed to investigate the risk factors of intraoperative
      anesthesia adverse events (IAAEs) in children with laryngeal diseases. METHODS:
      We retrospectively recruited 118 children with laryngeal diseases who underwent
      surgical therapy. Based on medical history and preoperative imaging diagnosis,
      the baseline data, including sex, age, weight, onset age, the number of
      operation, the degree of airway obstruction, the nature of disease, the location
      of disease, complications, tracheotomy, and trachea intubation, were defined and
      recorded. IAAEs, such as pulse oxygen saturation (SpO2) decline, heart rate (HR)
      decline, emergency orotracheal intubation, emergency tracheotomy, and remaining
      intubated postoperatively, were also recorded. The risk factors for IAAEs were
      identified using multivariate logistic regression model. RESULTS: Increasing
      severity of airway obstruction and the presence of pneumonia were risk factors
      for SpO2 and HR decline in children with laryngeal diseases. Older age,
      supraglottic rather than subglottic disease, and trachea intubation rather than
      unprotected airway during surgery were protective factors for SpO2 decline.
      Furthermore, severe airway obstruction increased risks of emergency orotracheal
      intubation and remaining intubated postoperatively, whereas supraglottic rather
      than subglottic disease were protective factors for emergency orotracheal
      intubation and remaining intubated postoperatively. Only HR decline was found to
      be associated with the presence of congenital heart disease. CONCLUSIONS: The
      severe airway obstruction increases the risk of SpO2 decline and HR decline as
      well as the possibility of perioperative emergency orotracheal intubation and
      remaining intubated postoperatively, whereas supraglottic surgery and surgery
      performed under endotracheal intubation reduce the incidence rates of these IAAEs
      in children with laryngeal diseases.

PMID- 27687448
TI  - The effect of obesity on the anatomical relationship of the popliteal artery and
      tibial nerve in the proximal and distal popliteal fossa: relevance to popliteal
      sciatic nerve block and a traceback technique using the popliteal artery.
AB  - STUDY OBJECTIVE: To determine the effect of body mass index (BMI) on the
      relationship of the popliteal artery to the sciatic and tibial nerves in the
      popliteal fossa. DESIGN: Prospective, observational study. SETTING: University
      medical center. SUBJECTS: One hundred patients scheduled for magnetic resonance
      imaging scans of the knee. MEASUREMENTS: BMI was recorded and magnetic resonance
      imaging scans were assessed at 3 different measurement points along the femur for
      the distance and angle between the popliteal artery and tibial nerve, or sciatic
      nerve if the sciatic nerve had not bifurcated at the measurement point. MAIN
      RESULTS: At the distal femur, the tibial nerve was a mean of 2.9 mm from the
      popliteal artery. The nerve was consistently posterior to the artery; however, it
      was variably located medial or lateral to the artery. At the 5- and 8-cm
      measurement points, the nerve was 10.0 and 16.1 mm (SD, 4.1 and 5.2 mm), and 31
      degrees  and 44 degrees  (SD, 15 degrees  and 16 degrees ) lateral to the
      popliteal artery, respectively. Zero degree was defined as directly posterior to
      the artery. Increasing BMI was correlated with increasing distance between the
      nerve and the artery at the 5- and 8-cm measurement points (r= 0.36 P> |t| .000
      and .45 P> |t| .002). CONCLUSIONS: At 5 cm proximal to the distal femoral
      condyles, the popliteal artery is a reliable sonographic landmark to locate the
      tibial nerve due to the close proximity and consistent location of the nerve 1 cm
      posterolateral to the artery, with only a moderate effect of BMI.

PMID- 27687449
TI  - Active perioperative patient warming using a self-warming blanket (BARRIER
      EasyWarm) is superior to passive thermal insulation: a multinational,
      multicenter, randomized trial.
AB  - STUDY OBJECTIVE: Incidence of inadvertent perioperative hypothermia is still
      high; therefore, present guidelines advocate "prewarming" for its prevention.
      Prewarming means preoperative patient skin warming, which minimizes
      redistribution hypothermia caused by induction of anesthesia. In this study, we
      compared the new self-warming BARRIER EasyWarm blanket with passive thermal
      insulation regarding mean perioperative patient core body temperature. DESIGN:
      Multinational, multicenter randomized prospective open-label controlled trial.
      SETTING: Surgical ward, operation room, postanesthesia care unit at 4 European
      hospitals. PATIENTS: A total of 246 adult patients, American Society of
      Anesthesiologists class I to III undergoing elective orthopedic; gynecologic; or
      ear, nose, and throat surgery scheduled for 30 to 120 minutes under general
      anesthesia. INTERVENTIONS: Patients received warmed hospital cotton blankets
      (passive thermal insulation, control group) or BARRIER EasyWarm blanket at least
      30 minutes before induction of general anesthesia and throughout the
      perioperative period (intervention group). MEASUREMENTS: The primary efficacy
      outcome was the perioperative mean core body temperature measured by a tympanic
      infrared thermometer. Secondary outcomes were hypothermia incidence, change in
      core body temperature, length of stay in postanesthesia care unit, thermal
      comfort, patient satisfaction, ease of use, and adverse events related to the
      BARRIER EasyWarm blanket. MAIN RESULTS: The BARRIER EasyWarm blanket
      significantly improved perioperative core body temperature compared with standard
      hospital blankets (36.5 degrees C, SD 0.4 degrees C, vs 36.3, SD 0.3 degrees C;
      P<.001). Intraoperatively, in the intervention group, hypothermia incidence was
      38% compared with 60% in the control group (P=.001). Postoperatively, the figures
      were 24% vs 49%, respectively (P=.001). Patients in the intervention group had
      significantly higher thermal comfort scores, preoperatively and postoperatively.
      No serious adverse effects were observed in either group. CONCLUSIONS:
      Perioperative use of the new self-warming blanket improves mean perioperative
      core body temperature, reduces the incidence of inadvertent perioperative
      hypothermia, and improves patients' thermal comfort during elective adult
      surgery.

PMID- 27687450
TI  - Clinical experiences of the continuous thoracolumbar interfascial plane (TLIP)
      block.

PMID- 27687451
TI  - Successful recovery after amniotic fluid embolism in a patient undergoing vacuum
      assisted vaginal delivery.
AB  - Amniotic fluid embolism (AFE) is a rare, catastrophic emergency that requires
      prompt recognition and treatment. Despite early recognition and supportive
      therapy, the morbidity and mortality remain high. We report a case of AFE after
      vacuum-assisted vaginal delivery resulting in hemodynamic collapse and subsequent
      multiorgan failure. Management included mechanical ventilation, extracorporeal
      membrane oxygenation, and continuous veno-venous hemodialysis. The patient was
      able to make a full recovery with minimal sequelae. In AFE with multiorgan
      failure, extracorporeal membrane oxygenation and continuous veno-venous
      hemodialysis can be valuable therapies. Proper management requires effective
      communication and the combined efforts of physicians of several disciplines. 

PMID- 27687452
TI  - Effect of Boussignac continuous positive airway pressure ventilation on Pao2 and
      Pao2/Fio2 ratio immediately after extubation in morbidly obese patients
      undergoing bariatric surgery: a randomized controlled trial.
AB  - STUDY OBJECTIVE: Pathophysiological changes after laparoscopic Roux-en-Y gastric
      bypass may increase the risk of pulmonary complications in morbidly obese
      patients. The purpose of the study was to assess the impact of immediate
      postextubation use of Boussignac continuous positive airway pressure (CPAP) on
      arterial oxygenation in morbidly obese patients undergoing laparoscopic Roux-en-Y
      gastric bypass. The hypothesis is that the use of CPAP may improve oxygenation in
      the postoperative period when compared to Venturi mask. DESIGN: Randomized
      controlled study. SETTING: A tertiary referral hospital. PATIENTS: Recruited
      morbidly obese adult patients undergoing laparoscopic Roux-en-Y gastric bypass.
      INTERVENTIONS: Boussignac CPAP or Venturi mask was randomly applied immediately
      after extubation in the operating room and was maintained during the first 2
      hours in the recovery room. MEASUREMENTS: Pao2 and Pao2/fraction of inspired
      oxygen (Fio2) ratio values were measured preoperatively and at 1 (T1), 2 (T2),
      and 24 hours (T24) after extubation, through arterial blood samples. Secondary
      outcomes (spirometric parameters) were measured at the same periods. For
      comparison between groups, Student t test, Mann-Whitney U nonparametric test, and
      chi(2) test were used. Statistical significance is at P < .05. MAIN RESULTS:
      Twenty-four patients were included, 12 in each group. There were no differences
      in preoperative evaluation. There were significant differences between groups in
      Pao2 and Pao2/Fio2 mean values at T1, T2, and T24, being superior in the
      Boussignac group. During the 24 hours postextubation, 9% of patients in the
      Boussignac group and 50% in the Venturi group had a Pao2 less than 60 mm Hg in at
      least 1 of the evaluations. After extubation, a Pao2/Fio2 ratio value less than
      300 was observed in all patients in the Venturi group and in 55% in Boussignac
      group in at least 1 of the evaluations. There were no differences in spirometric
      parameters between groups at T1, T2, and T24. CONCLUSIONS: Application of
      Boussignac CPAP for 2 hours after extubation improved oxygenation but did not
      improve forced expiratory volume at 1 second and forced vital capacity.

PMID- 27687453
TI  - Delayed onset and long-lasting hemidiaphragmatic paralysis and cranial nerve
      deficit after interscalene nerve block for rotator cuff repair in beach chair
      position.
AB  - Hemidiaphragmatic paralysis is the most common adverse effect associated with
      interscalene block. In most cases, it resolves with the resolution of nerve
      blockade with only an estimated incidence of 0.048% persisting for longer
      duration. Occasionally, interscalene block is also associated with recurrent
      laryngeal nerve block and seldom with cranial nerve paresis. We present a case of
      delayed onset and prolonged hemidiaphragmatic paralysis that was associated with
      3 cranial nerve deficits after interscalene nerve block for shoulder surgery
      performed under general anesthesia in the beach chair position. Etiology is
      unclear, but most likely multifactorial. 

PMID- 27687455
TI  - Risk stratification, perioperative and periprocedural management of the patient
      receiving anticoagulant therapy.
AB  - As a result of the aging US population and the subsequent increase in the
      prevalence of coronary disease and atrial fibrillation, therapeutic use of
      anticoagulants has increased. Perioperative and periprocedural management of
      anticoagulated patients has become routine for anesthesiologists, who frequently
      mediate communication between the prescribing physician and the surgeon and
      assess the risks of both thromboembolic complications and hemorrhage. Data from
      randomized clinical trials on perioperative management of antithrombotic therapy
      are lacking. Therefore, clinical judgment is typically needed regarding decisions
      to continue, discontinue, bridge, or resume anticoagulation and regarding the
      time points when these events should occur in the perioperative period. In this
      review, we will discuss the most commonly used anticoagulants used in outpatient
      settings and discuss their management in the perioperative period. Special
      considerations for regional anesthesia and interventional pain procedures will
      also be reviewed. 

PMID- 27687454
TI  - Dexmedetomidine acts as an oxidative damage prophylactic in rats exposed to
      ionizing radiation.
AB  - STUDY OBJECTIVE: To investigate the effects of dexmedetomidine on oxidative
      injury caused by ionizing radiation. DESIGN: Randomized controlled experimental
      study. SETTING: Department of radiation oncology and research laboratory of an
      academic hospital. INTERVENTIONS: Twenty-eight rats were randomized to 4 groups
      (n=7 per group). Group S rats were administered physiologic serum; group SR rats
      were administered physiologic serum and 10 Gy external ionizing radiation. Groups
      D100 and D200 were administered 100 and 200 MUg/kg dexmedetomidine
      intraperitoneally, respectively, 45 minutes before ionizing radiation.
      MEASUREMENTS: Liver, kidney, lung, and thyroid tissue and serum levels of
      antioxidant enzymes (glutathione peroxidase [GPX], superoxide dismutase, and
      catalase) and oxidative metabolites (advanced oxidation protein products,
      malondialdehyde, and nitrate/nitrite, and serum ischemia-modified albumin) were
      measured 6 hours postprocedure. MAIN RESULTS: In group SR, IR decreased
      antioxidant enzyme levels and increased oxidative metabolite levels (P<.05). In
      plasma, antioxidant enzyme levels were higher and oxidative metabolite levels
      were lower in groups D100 and D200 than in group SR (P<.01). In tissues, hepatic
      and lung GPX levels were higher in groups D100 and D200 than in group SR
      (P<.001). Renal and thyroid GPX levels were higher in D200 than in group SR
      (P<.01). Thyroid superoxide dismutase levels were higher in groups D100 and D200
      than in group SR (P<.01). Renal, lung, and thyroid catalase levels were higher in
      group D200 than in group SR (P<.01). Hepatic, renal, and lung advanced oxidation
      protein products and malondialdehyde levels were lower in groups D100 and D200
      than in group SR (P<.01). Hepatic, renal, and lung nitrate/nitrite levels were
      lower in group D200 than in group SR (P<.05). CONCLUSIONS: Dexmedetomidine
      preserves the antioxidant enzyme levels and reduces toxic oxidant metabolites.
      Therefore, it can provide protection from oxidative injury caused by ionizing
      radiation.

PMID- 27687456
TI  - Comparison of esophageal Doppler and plethysmographic variability index to guide
      intraoperative fluid therapy for low-risk patients undergoing colorectal surgery.
AB  - STUDY OBJECTIVE: This study aims to investigate if there is equivalence in
      volumes of fluid administered when intravenous fluid therapy is guided by Pleth
      Variability Index (PVI) compared to the established technology of esophageal
      Doppler in low-risk patients undergoing major colorectal surgery. DESIGN:
      Randomized controlled trial. SETTING: Operating room. PATIENTS: Forty low-risk
      patients undergoing elective colorectal surgery. INTERVENTION: Patients were
      monitored by esophageal Doppler and PVI probes and were randomized to have fluid
      therapy directed by using one of these technologies, with 250 mL boluses of
      colloid to maintain a maximal stroke volume, or a PVI of less than 14%.
      MEASUREMENTS: Absolute volumes of fluid volumes given intraoperatively were
      measured as were 24 hours fluid volumes. Perioperative measurements of lactate
      and base excess were recorded as were postoperative complications. MAIN RESULT:
      There was no significant difference between PVI and esophageal Doppler groups in
      mean total fluid administered (1286 vs 1520 mL, P=.300) or mean intraoperative
      fluid balance (+839 v+1145 mL, P=.150). CONCLUSIONS: PVI offers an entirely non
      invasive alternative for goal-directed fluid therapy in this group of patients.

PMID- 27687457
TI  - Seldinger technique for nasal intubation: a case series.
AB  - Nasotracheal intubation can be both challenging and traumatic, especially in
      cases of atypical anatomy. We present a series of 3 such cases in which an
      endotracheal tube introducer (bougie) was used to facilitate successful,
      atraumatic, nasotracheal intubation via Seldinger technique. The technique
      described can guide a nasotracheal tube through narrow nasal passages, small
      pharyngeal spaces, and past acute laryngeal approach angles, all without
      transoral manipulation of the tube. The technique is easy to perform, uses a
      routine skill set, and can be advantageous in numerous clinical scenarios. 

PMID- 27687458
TI  - Difficult mask ventilation: simple step to make the impossible, possible!
AB  - Mask ventilation is one of the most important skills in airway management.
      Difficulty in mask ventilation can become life threatening if it is associated
      with difficulty in intubation during general anesthesia. We report a potential
      impossible ventilation condition which was safely and easily overcome with
      appropriate innovative modification of an Opsite adhesive film. 

PMID- 27687459
TI  - Anesthesia-airway management in a newborn with syngnathia.

PMID- 27687460
TI  - Survey of external cephalic version for breech presentation and neuraxial
      blockade use.
AB  - STUDY OBJECTIVE: Neuraxial blockade may increase external cephalic version (ECV)
      success rates. This survey aimed to assess the frequency and characteristics of
      neuraxial blockade used to facilitate ECV. SETTING AND DESIGN: We surveyed
      Society for Obstetric Anesthesia and Perinatology members regarding ECV practice
      using a 15-item survey developed by 3 obstetric anesthesiologists and tested for
      face validity. The survey was e-mailed in January 2015 and again in February 2015
      to the 1056 Society of Obstetric Anesthesiology and Perinatology members. We
      present descriptive statistics of responses. PARTICIPANTS: Our survey response
      rate was 322 of 1056 (30.5%). MAIN RESULT: Neuraxial blockade was used for ECV
      always by 18 (5.6%), often by 52 (16.1%), sometimes by 98 (30.4%), rarely by 78
      (24.2%), and never by 46 (14.3%) of respondents. An anesthetic sensory block
      target was selected by 141 (43.8%) respondents, and analgesic by 102 (31.7%)
      respondents. Epidural drug doses ranged widely, including sufentanil 5-25 MUg;
      lidocaine 1% or 2% 10-20 mL, bupivacaine 0.0625% to 0.5% 6-15 mL, and ropivacaine
      0.2% 20 mL. Intrathecal bupivacaine was used by 182 (56.5%) respondents; the most
      frequent doses were 2.5 mg used by 24 (7.5%), 7.5 mg used by 35 (10.9%), and 12
      mg used by 30 (9.3%). CONCLUSIONS: Neuraxial blockade is not universally offered
      to facilitate ECV, and there is wide variability in neuraxial blockade
      techniques, in drugs and doses administered, and in the sensory blockade
      (anesthetic or analgesic) targeted. Future studies need to evaluate and remove
      barriers to allow for more widespread use of neuraxial blockade for pain relief
      and to optimize ECV success rates.

PMID- 27687461
TI  - National Survey of US academic anesthesiology chairs on clinician wellness.
AB  - STUDY OBJECTIVE: The prevalence of anesthesiology department wellness programs is
      unknown. A database of wellness programs is needed as a resource for departments
      attempting to respond to the Accreditation Council for Graduate Medical Education
      Anesthesiology Milestones Project. The purpose of this study was to survey
      academic anesthesiology chairs on wellness issues, characterize initiatives, and
      establish wellness contacts for a Wellness Initiative Database (WID). DESIGN: An
      Internet-based survey instrument was distributed to academic anesthesiology
      department chairs in the United States. SETTING: On-line. PATIENTS: None.
      INTERVENTIONS: None. MEASUREMENTS: Analysis for continuous variables used
      standard means, modes, and averages for individual responses; 95% confidence
      intervals for proportions were calculated by Wilson's method. MAIN RESULTS:
      Seventy-five (56.4%) responses (of a potential 133 programs) were obtained. Forty
      one (of 71 responders; 57.8%) expressed interest in participating in a WID, and
      33 (44%) provided contact information. Most (74.7%) had recently referred staff
      for counseling or wellness resources, yet many (79.5% and 67.1%, respectively)
      had never surveyed their department's interest in wellness resources. Thirty-four
      percent had a wellness resources repository. Of 22 wellness topics, 8 garnered
      >60% strong interest from respondents: Addiction Counseling, Sleep Hygiene, Peer
      Support Program, Stress Management, Conflict Management, Burnout Counseling, Time
      Management, and Dealing with Adverse Events Training. There was a statistically
      significant difference in interest between those willing to participate or not in
      the WID across most topics but no significant difference based on need for recent
      staff referral. CONCLUSIONS: The majority of chairs needed to recently refer a
      department member to wellness resources or counseling. Most were interested in
      participating in a WID, whereas a minority had gauged staff interest in wellness
      topics or had a wellness resource repository. Highest interest was in topics most
      related to function as an anesthesiologist. Those willing to participate in the
      database had statistically significant differences in interest across most
      wellness topics.

PMID- 27687462
TI  - An in vitro evaluation of the pressure generated during programmed intermittent
      epidural bolus injection at varying infusion delivery speeds.
AB  - STUDY OBJECTIVE: Programmed intermittent bolus injection of epidural anesthetic
      solution results in decreased anesthetic consumption and better patient
      satisfaction compared with continuous infusion, presumably by better spread of
      the anesthetic solution in the epidural space. It is not known whether the
      delivery speed of the bolus injection influences analgesia outcomes. The
      objective of this in vitro study was to determine the pressure generated by a
      programmed intermittent bolus pump at 4 infusion delivery speeds through open
      ended, single-orifice and closed-end, multiorifice epidural catheters. DESIGN: In
      vitro observational study. SETTING: Not applicable. PATIENTS: Not applicable.
      INTERVENTIONS: A CADD-Solis Pain Management System v3.0 with Programmed
      Intermittent Bolus Model 2110 was connected via a 3-way adapter to an epidural
      catheter and a digital pressure transducer. Pressures generated by delivery
      speeds of 100, 175, 300, and 400 mL/h of saline solution were tested with 4
      epidural catheters (2 single orifice and 2 multiorifice). These runs were
      replicated on 5 pumps. Analysis of variance was used to compare the mean peak
      pressures of each delivery speed within each catheter group (single orifice and
      multiorifice). MAIN RESULTS: Thirty runs at each delivery speed were performed
      with each type of catheter for a total of 240 experimental runs. Peak pressure
      increased with increasing delivery speeds in both catheter groups (P<.001). Peak
      pressures were higher with the multiorifice catheter compared with the single
      orifice catheter at all delivery speeds (P<.001, for all). CONCLUSION: Using a
      pump designed for programmed intermittent infusion boluses, the delivery speed of
      saline solution through epidural catheters was directly related to the peak
      pressures. Future work should evaluate whether differences in the delivery speed
      of anesthetic solution into the epidural space correlate with differences in the
      duration and quality of analgesia during programmed intermittent epidural bolus
      delivery.

PMID- 27687463
TI  - Confirmation of laryngeal mask airway placement by ultrasound examination: a
      pilot study.
AB  - STUDY OBJECTIVE: We sought to validate ultrasound against other established
      methods of confirming laryngeal mask airway (LMA) placement. DESIGN: An
      observational study. SETTING: A university teaching hospital, operating
      department. PATIENTS: Fifty-eight patients undergoing general anesthesia using an
      LMA Supreme supraglottic airway device. INTERVENTIONS: The position of the LMA
      was assessed by ultrasound in 3 planes: the pharynx, the larynx, and along the
      cranial-caudal axis in the midline. The leakage test at 20 cm H2O and fiberoptic
      examination were also undertaken independently, with the latter being used to
      detect suboptimal placement (in which case, the LMA was reinserted).
      MEASUREMENTS: We scored the position of the LMA based on the location of the cuff
      and whether it had inflated correctly in each of the 3 planes. This score was
      converted to correspond with the leakage test grading system. We tested the
      strength of the correlation between the scores and the sensitivity and
      specificity for predicting reinsertion. MAIN RESULTS: Seven patients (12.1%)
      required LMA reinsertion, and ventilation was inadequate in a further 6 (10.3%).
      Three patients (5.2%) developed laryngospasm and inspiratory stridor after
      insertion resulting in inadequate ventilation, but none needed reinsertion as
      optimal placement was confirmed by fiberscope. Spearman coefficient of rank
      correlation between the leakage test and ultrasound examination was 0.713 (P<
      .0001). The kappa test and Bland-Altman analysis showed good agreement between
      the 2 scoring systems (weighted kappa = 0.605, standard error = 0.086). An
      ultrasound examination score equating to grade 3 in the leakage test predicted
      the need for reinsertion with a sensitivity and specificity of 85.7% and 94.1%,
      respectively. CONCLUSIONS: Ultrasound examination is a fast, noninvasive and
      reliable means of detecting LMA misplacement that agrees closely with the leakage
      test. Ultrasound is as effective as a fiberoptic examination to confirm LMA
      placement and indicate the need for reinsertion, but does not require ventilation
      to be interrupted.

PMID- 27687464
TI  - Effects of music on sedation depth and sedative use during pediatric dental
      procedures.
AB  - STUDY OBJECTIVE: The study aimed to investigate the effects of listening to music
      or providing sound isolation on the depth of sedation and need for sedatives in
      pediatric dental patients. DESIGN: Prospective, randomized, and controlled study.
      SETTING: Tertiary, university hospital. PATIENTS: In total, 180 pediatric
      patients, American Society of Anesthesiologists physical status I and II, who
      were scheduled for dental procedures of tooth extraction, filling, amputation,
      and root treatment. INTERVENTIONS: Patients were categorized into 3 groups:
      music, isolation, and control. During the procedures, the patients in the music
      group listened to Vivaldi's The Four Seasons violin concertos by sound-isolating
      headphones, whereas the patients in the isolation group wore the headphones but
      did not listen to music. All patients were sedated by 0.1 mg/kg midazolam and 1
      mg/kg propofol. During the procedure, an additional 0.5 mg/kg propofol was
      administered as required. MEASUREMENTS AND MAIN RESULTS: Bispectral index was
      used for quantifying the depth of sedation, and total dosage of the propofol was
      used for sedative requirements. The patients' heart rates, oxygen saturations,
      and Observer's Assessment of Alertness and Sedation Scale and bispectral index
      scores, which were monitored during the operation, were similar among the groups.
      In terms of the amount of propofol used, the groups were similar. Prolonged
      postoperative recovery cases were found to be significantly frequent in the
      control group, according to the recovery duration measurements (P = .004).
      CONCLUSIONS: Listening to music or providing sound isolation during pediatric
      dental interventions did not alter the sedation level, amount of medication, and
      hemodynamic variables significantly. This result might be due to the deep
      sedation levels reached during the procedures. However, listening to music and
      providing sound isolation might have contributed in shortening the postoperative
      recovery duration of the patients.

PMID- 27687465
TI  - Chlorhexidine-related refractory anaphylactic shock: a case successfully
      resuscitated with extracorporeal membrane oxygenation.
AB  - IMPORTANCE: We report a patient with a life-threatening anaphylactic reaction to
      a chlorhexidine-coated central venous catheter, confirmed with a high serum level
      of chlorhexidine-specific IgE. To our knowledge, this is the first case
      successfully resuscitated using extracorporeal membrane oxygenation (ECMO). Great
      caution is required when using chlorhexidine and chlorhexidine-impregnated
      catheters, given that its widespread use has the potential to sensitize certain
      patients and may result in life-threatening anaphylaxis on subsequent exposure.
      OBSERVATIONS: A case report of a single patient with life-threatening
      anaphylactic shock to chlorhexidine, who was successfully resuscitated using
      ECMO. CONCLUSIONS: We have designed a flowchart for the diagnosis and management
      of severe anaphylaxis. This case report highlights the potential for
      chlorhexidine to be a source for the development of refractory anaphylactic
      shock. We suggest that ECMO may save the lives of patients with severe
      bronchospasm and refractory anaphylactic shock secondary to chlorhexidine.

PMID- 27687466
TI  - Assessing electronic interruptions experienced by an anesthesiology clinical
      director.
AB  - STUDY OBJECTIVE: The purpose of this study was to assess the workflow
      interruptions on an anesthesiology clinical director (CD). By assessing the
      interruptions on the CD, we hypothesize that these frequent interruptions would
      prohibit the CD from medical direction of residents or certified nurse
      anesthetists in operating rooms. DESIGN: Cellular phone data were obtained from
      Verizon Wireless statements over 10 months, August 2012 through May 2013. These
      data were from a single cellular phone carried by the anesthesia CD and
      subsequent overnight anesthesiologist 24 hours a day. The data obtained from the
      billing records included number of calls, date and time call occurred, number of
      minutes per call, and number of texts received. SETTING: These calls occurred in
      the operating room. PATIENTS: Not applicable. INTERVENTION: Not applicable.
      MEASUREMENTS: Phone calls, texts, and pager interruptions. MAIN RESULTS: A total
      of 19,924 calls and 19,803 texts were received by the CD. The phone calls minutes
      for this period were 31,236 minutes. A total of 15,831 (80%) of the calls
      occurred during this period (0600-1800). A total of 24 489 minutes (78%) of the
      total minutes occurred during this time. CONCLUSION: This study revealed that
      distracting events are frequent for an anesthesiology CD. The quantity of
      cellular phone interruptions, both calls and texts, by the anesthesiology CD was
      considered high. These calls occurred mainly during prime operating room time and
      utilization. As the CD is an integral part of the perioperative management team,
      they are expected to answer and return calls and texts promptly. Operating room
      efficiency and staff satisfaction decline if responses to these calls and texts
      are delayed. Although the nature of these distractions and interruptions can be
      viewed as having a positive or negative effect, many of these events are
      necessary to efficiently run the operating rooms.

PMID- 27687467
TI  - A temporal analysis of opioid use, patient satisfaction, and pain scores in
      colorectal surgery patients.
AB  - BACKGROUND: Recent health care policy changes promote objective measurements of
      patient satisfaction with care provided during hospitalization. Acute
      postsurgical pain is a significant medical problem and strongly impacts patient
      experience and patient satisfaction. Multimodal analgesic pathways are used for
      acute pain management, but opioid medications remain a mainstay of treatment.
      Opioid use is increasing in the outpatient setting, but opioid use trends in the
      inpatient postsurgical setting are not well known. We hypothesized that use of
      opioid medications has increased over time along with decrease in postoperative
      pain scores and increase in pain-related patient satisfaction. METHODS: In this
      single-center study, we studied the trends and correlation in the average daily
      pain scores, opioid consumption, and patient satisfaction scores as measured by
      pain-related patient satisfaction questions in the Hospital Consumer Assessment
      of Healthcare Providers and System survey. Pain scores and opioid use data were
      obtained from electronic health records, vital signs monitoring, and medication
      databases. Adult patients who had nonemergent colorectal surgeries between
      January 2009 and December 2012 were included. RESULTS: We found no significant
      trend in opioid use or pain-related patient satisfaction scores. There was an
      average annual increase of 0.3 (98.3% confidence interval, 0.2-0.4; P< .001) in
      average daily pain score from 2.8 +/- 1.5 to 3.8 +/- 1.5. The univariable
      associations between time-weighted pain score, average daily opioid dose, and
      pain-related patient satisfaction score were all highly significant. CONCLUSION:
      In this retrospective cohort study, opioid use and pain-related patient
      satisfaction scores were stable over time. Pain-related patient satisfaction
      scores were negatively associated with both pain score and opioid dose. The
      associations we report should not be considered evidence of a causal
      relationship.

PMID- 27687468
TI  - Nerve stimulator-guided pudendal nerve block vs general anesthesia for
      postoperative pain management after anterior and posterior vaginal wall repair: a
      prospective randomized trial.
AB  - STUDY OBJECTIVE: Compare the effectiveness of nerve stimulator-guided pudendal
      nerve block (PNB) vs general anesthesia (GA) for anterior and posterior (AP)
      colporrhaphy in terms of pain relief and analgesic consumption within 24 and 48
      hours postoperatively. DESIGN: Prospective randomized trial. PATIENTS: Fifty
      seven patients whose ages ranged between 20 and 53 years scheduled to undergo AP
      colporrhaphy due to the presence of cystorectocele. INTERVENTIONS: Patients were
      randomly assigned into 2 groups receiving either nerve stimulator-guided PNB (n =
      28) or GA (n = 29). A total volume of 0.7 mL/kg of the local anesthetic mixture
      was injected at 4 sites. MAIN RESULTS: Both groups were similar with respect to
      age, weight, height, and surgery duration. There was a significant difference in
      average pain scores within the first and second postoperative days (P values =
      .005 and .004, respectively). Total analgesic consumption (ketoprofen and
      tramadol) was significantly lower in the PNB within the first (P values = .018
      and .010) and second postoperative days (P values = .041 and .011), respectively.
      Return to normal daily activity was significantly (P< .0001) shorter in the PNB
      group compared with the GA group (3.6 days vs 12.2 days). A total of 71.4% of the
      patients in the PNB group were satisfied compared with 27.8% in the GA group (P<
      .0001). Surgeon satisfaction was significantly higher in the PNB group (82.1% vs
      34.5%, P< .0001). CONCLUSION: This randomized controlled trial demonstrated that
      nerve stimulator-guided PNB could be used as an alternative to GA for AP repair
      of stages I and II prolapse because it is associated with less postoperative pain
      and analgesic consumption, in addition to shorter duration of recovery.

PMID- 27687469
TI  - Remediation for fellowship training: doing what is best for trainee and patient!

PMID- 27687471
TI  - Impact of Hair Removal on Surgical Site Infection Rates: A Prospective Randomized
      Noninferiority Trial.
AB  - BACKGROUND: Despite substantial prevention efforts, surgical site infections
      (SSIs) remain the most common health care-associated infection. It is unclear
      whether the Centers for Disease Control and Prevention recommendation to leave
      hair intact preoperatively reduces SSIs. STUDY DESIGN: A single-center,
      prospective, randomized, clinical trial was conducted from October 2009 to
      February 2015 in a 325-bed multispecialty, tertiary care teaching hospital to
      test the noninferiority of clipping hair to no hair removal in the prevention of
      SSIs. A total of 4,908 adults scheduled for elective general surgical procedures
      were screened for study participation. Of these, 600 were approached but refused,
      and 2,630 were excluded. Patients were randomized 1:1 to either the clipped group
      (n = 834) or the not-clipped group (n = 844). The clipped group had hair at the
      surgical site removed using disposable electric clippers. Of the randomized
      patients, 1,543 (768 in the clipped group and 775 in the not-clipped group)
      completed follow-up. The primary endpoint was the proportion of patients who
      could be evaluated and who had no SSI, as defined by CDC criteria. RESULTS:
      Baseline demographic, clinical, and surgical characteristics were similar between
      groups. The overall rate of SSI in the per-protocol analysis was 6.12% (47 of
      768) in the clipped group and 6.32% (49 of 775) in the not-clipped group
      (absolute risk difference -0.20%; 95% CI -2.61% to 2.21%), p = 0.037). Because
      the absolute risk difference confidence interval included the prespecified
      noninferiority margin of 2%, we were unable to definitively demonstrate
      noninferiority for clipping hair. CONCLUSIONS: Surgical site infection rates were
      similar whether hair was clipped or not in patients undergoing general surgical
      procedures.

PMID- 27687470
TI  - Adolescent cortical thickness pre- and post marijuana and alcohol initiation.
AB  - Cortical thickness abnormalities have been identified in youth using both alcohol
      and marijuana. However, limited studies have followed individuals pre- and post
      initiation of alcohol and marijuana use to help identify to what extent
      discrepancies in structural brain integrity are pre-existing or substance
      related. Adolescents (N=69) were followed from ages 13 (pre-initiation of
      substance use, baseline) to ages 19 (post-initiation, follow-up). Three subgroups
      were identified, participants that initiated alcohol use (ALC, n=23, >20 alcohol
      use episodes), those that initiated both alcohol and marijuana use (ALC+MJ, n=23,
      >50 marijuana use episodes) and individuals that did not initiate either
      substance regularly by follow-up (CON, n=23, <3 alcohol use episodes, no
      marijuana use episodes). All adolescents underwent neurocognitive testing,
      neuroimaging, and substance use and mental health interviews. Significant group
      by time interactions and main effects on cortical thickness estimates were
      identified for 18 cortical regions spanning the left and right hemisphere
      (ps<0.05). The vast majority of findings suggest a more substantial decrease, or
      within-subjects effect, in cortical thickness by follow-up for individuals who
      have not initiated regular substance use or alcohol use only by age 19; modest
      between-group differences were identified at baseline in several cortical regions
      (ALC and CON>ALC+MJ). Minimal neurocognitive differences were observed in this
      sample. Findings suggest pre-existing neural differences prior to marijuana use
      may contribute to initiation of use and observed neural outcomes. Marijuana use
      may also interfere with thinning trajectories that contribute to morphological
      differences in young adulthood that are often observed in cross-sectional studies
      of heavy marijuana users.

PMID- 27687472
TI  - A new multiple sex chromosome system X1X1X2X2/X1Y1X2Y2 in Siluriformes:
      cytogenetic characterization of Bunocephalus coracoideus (Aspredinidae).
AB  - We analyzed one Bunocephalus coracoideus population from the Negro River basin
      using cytogenetic techniques. The results showed a diploid number of 42
      chromosomes in both sexes, with the karyotypic formula 4m + 14sm + 24a and
      fundamental number (FN) = 60 for females and the formula 5m + 14sm + 23a and FN =
      61 for males, constituting an X1X1X2X2/X1Y1X2Y2 multiple sex chromosome system.
      The constitutive heterochromatin is distributed in the pericentromeric regions of
      most of the chromosomes, except for the sex chromosomes, of which the X1, X2, and
      Y1 chromosomes were euchromatic and the Y2 chromosome was partially
      heterochromatic. 18S rDNA mapping confirmed the presence of nucleolar organizer
      regions on the short arms of the fifth chromosomal pair for both sexes. The 5S
      rDNA is present in the terminal regions of the short arms on the 2nd, 10th, and
      12th pairs and on the X2 chromosome of both sexes; however, we observed
      variations in the presence of these ribosomal cistrons on the Y1 chromosome, on
      which the cistrons are pericentromeric, and on the Y2 chromosome, on which these
      cistrons are present in the terminal portions of the short and long arms.
      Telomeric sequences are located in the terminal regions of all of the
      chromosomes, particularly conspicuous blocks on the 10th and 12th pairs and
      internal telomeric sequences in the centromeric regions of the 1st, 6th, and 9th
      pairs for both sexes. This work describes an new sex chromosomes system for the
      Siluriformes and increases our genetic knowledge of the Aspredinidae family.

PMID- 27687473
TI  - On the mechanism of ubiquinone mediated photocurrent generation by a reaction
      center based photocathode.
AB  - Upon photoexcitation, the reaction center (RC) pigment-proteins that facilitate
      natural photosynthesis achieve a metastable separation of electrical charge among
      the embedded cofactors. Because of the high quantum efficiency of this process,
      there is a growing interest in their incorporation into biohybrid materials for
      solar energy conversion, bioelectronics and biosensing. Multiple
      bioelectrochemical studies have shown that reaction centers from various
      photosynthetic organisms can be interfaced with diverse electrode materials for
      the generation of photocurrents, but many mechanistic aspects of native protein
      functionality in a non-native environment is unknown. In vivo, RC's catalyse
      ubiquinone-10 reduction, protonation and exchange with other lipid phase
      ubiquinone-10s via protein-controlled spatial orientation and protein
      rearrangement. In contrast, the mechanism of ubiquinone-0 reduction, used to
      facilitate fast RC turnover in an aqueous photoelectrochemical cell (PEC), may
      not proceed via the same pathway as the native cofactor. In this report we show
      truncation of the native isoprene tail results in larger RC turnover rates in a
      PEC despite the removal of the tail's purported role of ubiquinone headgroup
      orientation and binding. Through the use of reaction centers with single or
      double mutations, we also show the extent to which two-electron/two-proton
      ubiquinone chemistry that operates in vivo also underpins the ubiquinone-0
      reduction by surface-adsorbed RCs in a PEC. This reveals that only the ubiquinone
      headgroup is critical to the fast turnover of the RC in a PEC and provides
      insight into design principles for the development of new biophotovoltaic cells
      and biosensors.

PMID- 27687474
TI  - Embryo-larval exposure to atrazine reduces viability and alters oxidative stress
      parameters in Drosophila melanogaster.
AB  - The herbicide atrazine has been used worldwide with subsequent residual
      contamination of water and food, which may cause adverse effects on non-target
      organisms. Animal exposure to this herbicide may affect development, reproduction
      and energy metabolism. Here, the effects of atrazine regarding survival and redox
      metabolism were assessed in the fruit fly D. melanogaster exposed during
      embryonic and larval development. The embryos (newly fertilized eggs) were
      exposed to different atrazine concentrations (10MUM and 100MUM) in the diet until
      the adult fly emerged. Pupation and emergence rates, developmental time and sex
      ratio were determined as well as oxidative stress parameters and gene expression
      of the antioxidant defence system were evaluated in newly emerged male and female
      flies. Atrazine exposure reduced pupation and emergence rates in fruit flies
      without alterations to developmental time and sex ratio. Different redox
      imbalance patterns were observed between males and females exposed to atrazine.
      Atrazine caused an increase in oxidative damage, reactive oxygen species
      generation and antioxidant capacity and decreased thiol-containing molecules.
      Further, atrazine exposure altered the mRNA expression of antioxidant genes
      (keap1, sod, sod2, cat, irc, gss, gclm, gclc, trxt, trxr-1 and trxr-2).
      Reductions in fruit fly larval and pupal viability observed here are likely
      consequences of the oxidative stress induced by atrazine exposure.

PMID- 27687476
TI  - Consequences of the Convergence of Multiple Alternate Pathways on the Estrogen
      Receptor in the Treatment of Metastatic Breast Cancer.
AB  - Endocrine therapy is the usual first-line therapy for patients with hormone
      receptor-positive metastatic breast cancer. However, resistance to hormone
      therapies frequently occurs during the course of treatment. Growing understanding
      of the signal cascade of estrogen receptors and the signaling pathways that
      interact with estrogen receptors has revealed the complex role of these receptors
      in cell growth and proliferation, and on the mechanism in development of
      resistance. These insights have led to the development of targeted therapies that
      may prove to be effective options for the treatment of breast cancer and may
      overcome hormone therapy resistance. This article reviews current understanding
      of the cellular receptor signaling pathways that interact with estrogen
      receptors. It also reviews data from recent ongoing clinical trials that examine
      the effects of targeted therapies, which might interfere with estrogen receptor
      pathways and might reduce or reverse resistance to traditional, sequential,
      single-agent endocrine therapy.

PMID- 27687475
TI  - Structures of the colossal RyR1 calcium release channel.
AB  - Ryanodine receptors (RyRs) are intracellular cation channels that mediate the
      rapid and voluminous release of Ca2+ from the sarcoplasmic reticulum (SR) as
      required for excitation-contraction coupling in cardiac and skeletal muscle.
      Understanding of the architecture and gating of RyRs has advanced dramatically
      over the past two years, due to the publication of high resolution cryo-electron
      microscopy (cryoEM) reconstructions and associated atomic models of multiple
      functional states of the skeletal muscle receptor, RyR1. Here we review recent
      advances in our understanding of RyR architecture and gating, and highlight
      remaining gaps in understanding which we anticipate will soon be filled.

PMID- 27687477
TI  - Interactional synchrony and negative symptoms: An outcome study of body-oriented
      psychotherapy for schizophrenia.
AB  - OBJECTIVE: We sought to assess the efficacy of a manualized body-oriented
      psychotherapy (BPT) intervention for schizophrenia, by focusing on improvement of
      negative symptoms and on changes in interactional synchrony. We also explored
      aspects of a phenomenological theory of schizophrenia, which states that negative
      symptoms should be understood within an encompassing disturbance of subjectivity
      and intersubjectivity. METHOD: Sixteen persons with schizophrenia participated in
      10 weeks of BPT. General psychiatric symptomatology and negative symptoms were
      assessed before and after therapy. Interactional synchrony was assessed via cross
      correlations of movements between patient and interviewer in interviews conducted
      before and after therapy. RESULTS: Psychiatric symptomatology and negative
      symptoms significantly improved with a medium effect size. We also demonstrated a
      significant increase in interactional synchrony with a strong effect size. Post
      hoc analyses showed a significant increase only with open-ended interviews
      conducted by the same interviewer. Furthermore, we explored the correlation
      between negative symptoms and interactional synchrony, finding a large inverse
      relationship. CONCLUSIONS: BPT for schizophrenia may effectively reduce patients'
      negative symptoms and psychiatric symptomatology. Moreover, it may yield some
      recovery of pre-reflective social relations. Further evidence of the specific
      relation between negative symptoms and interactional synchrony would support a
      phenomenologically informed holistic view of schizophrenia.

PMID- 27687478
TI  - Neem (Azadirachta indica): towards the ideal insecticide?
AB  - Pesticide resistance is going to change rapidly our antibiotics and insecticides
      arsenal. In this scenario, plant-derived natural products are considered valuable
      candidates to reverse this negative trend. Growing research attention is focused
      on neem (Azadirachta indica, Meliaceae), exploring the utility of its products as
      insecticides and antibiotics. In this review, we summarised the knowledge on neem
      oil and neem cake by-products in arthropod pest control, with special reference
      to mosquito vectors of public health importance. To the best of our knowledge,
      neem-borne products currently showed effective and eco-friendly features,
      including little non-target effects, multiple mechanisms of action, low cost,
      easy production in countries with limited industrial facilities. In particular,
      the potentiality of neem cake as ideal and affordable source of mosquitocidal
      compounds in anopheline and aedine control programmes is outlined. Overall, we
      propose the employ of neem-based products as an advantageous alternative to build
      newer and safer arthropod control tools.

PMID- 27687479
TI  - Rab3a and Rab10 are regulators of lysosome exocytosis and plasma membrane repair.
AB  - Disruption of the cell plasma membrane can occur due to mechanical damage, pore
      forming toxins, etc. Resealing or plasma membrane repair (PMR) is the emergency
      response required for cell survival. It is triggered by Ca2+ entering through the
      disruption, causing organelles such as lysosomes located underneath the plasma
      membrane to fuse rapidly with the adjacent plasma membrane. We have recently
      identified some of the molecular traffic machinery that is involved in this vital
      process. Specifically, we showed that 2 members of the Rab family of small
      GTPases, Rab3a and Rab10, are essential for lysosome exocytosis and PMR in cells
      challenged with a bacterial toxin, streptolysin-O (SLO). Additionally, we showed
      that Rab3a regulates PMR via the interaction with 2 effectors, synaptotagmin-like
      protein 4a (Slp4-a) and nonmuscle myosin heavy chain IIA (NMHC IIA), the latter
      being identified for the first time as a Rab3a effector. This tripartite complex
      is essential for the positioning of the peripheral lysosomes responsible for PMR.
      In cells lacking any of the components of this tripartite complex, lysosomes were
      concentrated in the perinuclear region and absent in the periphery culminating
      with PMR inhibition.

PMID- 27687481
TI  - Abstracts of the 36th Scandinavian Congress of Rheumatology, Reykjavik, Iceland,
      September 1st-3rd, 2016.

PMID- 27687482
TI  - The IL-20 receptor axis in immune-mediated inflammatory arthritis: novel links
      between innate immune recognition and bone homeostasis.
AB  - The treatment of rheumatoid arthritis (RA) and spondyloarthritis (SpA) was
      transformed a little over a decade ago by the introduction of agents neutralizing
      the pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha. Nevertheless,
      some patients do not achieve remission and the inhibition of the normal immune
      system with current drugs increases the risk of infection. The interleukin (IL)
      20 receptor (IL-20R) axis is pivotal for tissue homeostasis. By contrast, this
      axis does not seem to directly activate cells of the immune system. Thus,
      modulation of the IL-20R axis might not result in increased risk of infection.
      The IL-20R axis consists of the three cytokines IL-19, IL-20, and IL-24 (termed
      the IL-20R cytokines) and their shared receptors. All three cytokines bind the
      receptor complex of IL-20R2/IL-20R1 whereas only IL-20 and IL-24 also bind the
      receptor complex of IL-20R2/IL-22R1. This short review describes how the IL-20R
      axis could be a novel link between innate immune recognition and bone
      homeostasis. The IL-20R cytokines are produced in response to both danger
      associated molecular patterns and immune complexes formed by RA-associated
      autoantibodies. This could be of importance because these mediators can thus be
      present even in situations without inflammation. IL-19 shows anti-inflammatory
      properties in arthritis through IL-20R1. IL-20 and IL-24 through IL-22R seem to
      participate in the recruitment of mononuclear cells to the synovial joint and to
      sites of bone erosion in particular. Our results indicate that dual inhibition of
      IL-20 and IL-24 or attenuation of the shared IL-22R subunit could have a
      beneficial effect on radiographic progression, especially in seropositive RA.

PMID- 27687480
TI  - Enzymatic activities of circulating plasma proteasomes in newly diagnosed
      multiple myeloma patients treated with carfilzomib, lenalidomide and
      dexamethasone.
AB  - The proteasome inhibitor carfilzomib is highly effective in the treatment of
      multiple myeloma. It irreversibly binds the chymotrypsin-like active site in the
      beta5 subunit of the 20S proteasome. Despite impressive response rates when
      carfilzomib is used in combination with immunomodulatory agents in newly
      diagnosed multiple myeloma patients; no biomarker exists to accurately predict
      response and clinical outcomes. We prospectively assessed the activity in
      peripheral blood of the chymotrypsin-like (CHYM), caspase-like (CASP) and trypsin
      like (TRYP) proteolytic sites in 45 newly diagnosed multiple myeloma patients
      treated with eight cycles of carfilzomib, lenalidomide and dexamethasone (CRd)
      (NCT01402284). Samples were collected per protocol and proteasome activity
      measured through a fluorogenic assay. Median CHYM levels after one dose of
      carfilzomib decreased by >70%. CHYM and CASP activity decreased throughout
      treatment reaching a minimum after eight cycles of treatment. Higher levels of
      proteasome activity associated with higher disease burden (r > 0.30; p < 0.05)
      and higher disease stage (0.10 < p <0.20). No association was found with the
      probability of achieving a complete response, minimal residual disease negativity
      or time to best response. Further studies evaluating proteasome activity in
      malignant plasma cells may help elucidate how proteasome activity can be used as
      a biomarker in multiple myeloma.

PMID- 27687483
TI  - Hand osteoarthritis: current knowledge and new ideas.
AB  - Hand osteoarthritis (OA) is a prevalent disease that can lead to substantial pain
      and physical disability. Currently, no disease-modifying drugs exist for the
      treatment of OA. Most OA research has been conducted on knee OA and we have
      limited knowledge about disease mechanisms in hand OA. During her research
      career, Ida K Haugen (IKH) has focused on the epidemiology of hand OA and imaging
      techniques. She has established a large international network, providing the
      opportunity to study the epidemiology of hand OA in large international OA
      cohorts. In the Framingham study, she found that symptomatic hand OA was present
      in 16% of women and 8% of men aged between 40 and 84 years. In her PhD thesis,
      IKH studied the reliability and validity of magnetic resonance imaging (MRI) in
      hand OA. In collaboration with OMERACT (Outcome Measures in Rheumatology), an MRI
      scoring system for hand OA was developed. MRI is more sensitive than radiographs
      for detecting structural abnormalities. Synovitis, as detected by both MRI and
      ultrasound, is associated with pain and predicts future disease progression.
      Hence, synovitis may represent a treatment target in hand OA. Her future research
      plans include the observational Nor-Hand study and a placebo-controlled
      randomized trial on methotrexate (MTX) in hand OA. The data collection of 300
      patients in the Nor-Hand study is ongoing, and focuses on causes of pain and
      novel imaging techniques to assess inflammation in hand OA. In a future clinical
      trial, patients with moderate to severe long-lasting pain and inflammation will
      be treated with MTX and the effect on pain and inflammation will be explored.

PMID- 27687484
TI  - Optimizing biological treatments for rheumatoid arthritis.
AB  - The area of rheumatoid arthritis (RA) treatment has been revolutionized during
      the last decades with the development of biological therapies and their
      introduction into daily clinical practice contributing greatly to this dramatic
      change. However, several aspects of the use of these highly effective but
      expensive therapies remain far from optimal. To date, there is no clear evidence
      for the optimal sequence of biological agents, and the choice of a second- or
      third-line biologic is random. The effect of drug levels and the presence of
      neutralizing anti-drug antibodies remain unclear. In addition, the identification
      of prognostic factors of response, both clinical and histopathological, is
      crucial for a more individualized treatment approach.

PMID- 27687486
TI  - Small molecule induces Wnt asymmetry in cancer.

PMID- 27687487
TI  - Individualized follicle-stimulating hormone dosing and in vitro fertilization
      outcome in agonist downregulated cycles: a systematic review.
AB  - INTRODUCTION: This systematic review examines whether individualized gonadotropin
      dosing in in vitro fertilization (IVF) leads to better outcomes with respect to
      safety, costs, and live birth rates compared with standard dosing. MATERIAL AND
      METHODS: Electronic databases searched were PubMed, Embase, and Cochrane. The
      primary outcome was live birth rate. The secondary outcomes included pregnancy
      rate, costs, and safety. Papers were critically appraised by two reviewers.
      RESULTS: A total of 7022 articles were retrieved and assessed for eligibility, of
      which seven randomized controlled trials were selected. All studies used
      gonadotropin-releasing hormone agonist co-treatment. Clinical and methodological
      heterogeneity was present, so data could not be pooled for meta-analysis. Only
      one study, that mainly included women with a good prognosis, revealed an
      increased chance of ongoing pregnancy in the individualized dosing group compared
      with standard treatment. With respect to safety, individualized dosing might
      reduce the occurrence of hyper-response and ovarian hyperstimulation syndrome,
      without affecting the outcome of pregnancy. In predicted poor responders, higher
      than standard dosages do not reduce the incidence of poor response. A cost
      efficacy analysis was not performed in any of the studies included. CONCLUSION:
      It is currently not possible to conclude whether individualized dosing leads to
      higher pregnancy or live birth rates compared with standard dosing, because
      evidence from well-designed studies that are adequately powered for one of these
      outcomes is lacking. So, large well-designed studies that evaluate the impact of
      individualized dosing on live birth rates are needed to assess whether
      individualized dosing should become the standard in IVF practice.

PMID- 27687488
TI  - Your Best Life: Breaking the Cycle: The Power of Gratitude.

PMID- 27687489
TI  - CORR Insights(r): Osteochondritis Dissecans Lesions in Family Members: Does a
      Positive Family History Impact Phenotypic Potency?

PMID- 27687490
TI  - CORR (r) International-Asia-Pacific: Making the Transition From Training to
      Practice: A Guide For Young Surgeons in the Asia-Pacific Region.

PMID- 27687491
TI  - Letter to the Editor: New Definition for Periprosthetic Joint Infection: From the
      Workgroup of the Musculoskeletal Infection Society.

PMID- 27687493
TI  - The peak velocity derived from the Carminatti Test is related to physical match
      performance in young soccer players.
AB  - The aim of this study was to examine the relationship between the peak velocity
      derived from the Carminatti Test (T-CAR) (PVT-CAR) and physical match performance
      in young soccer players. Thirty-three youth soccer players were recruited from 2
      non-professional clubs. Friendly matches and small-sided game were performed.
      Physical match demands were assessed using Global Positioning System (GPS)
      technology. On a separate occasion, the players were submitted to the T-CAR.
      Players were categorised into 3 groups based on their T-CAR performance: Low (PVT
      CAR <= P33), Intermediate (P33 > PVT-CAR < P66) and High (PVT-CAR >= P66). The
      PVT-CAR (15.5 +/- 0.7 km.h-1) was significantly related to high-intensity
      activities (HIA; r = 0.78, P < 0.001), high-intensity running (HIR; r = 0.66, P <
      0.001), sprinting (r = 0.62, P < 0.001) and total distance (TD) covered (r =
      0.47, P < 0.01) during friendly matches. The PVT-CAR was strongly correlated with
      the amount of HIA (r = 0.81, P < 0.001), HIR (r = 0.85, P < 0.001) and TD covered
      (r = 0.81, P < 0.001) during small-sided game. No significant correlation was
      observed between the PVT-CAR and distance of sprinting (r = 0.49, P = 0.067)
      during small-side game. Furthermore, players in the High group covered
      significantly more TD (10%) and did more HIA (42%), sprinting (31%) and HIR (25%)
      during friendly matches compared to the players classified as having Low
      performance on the T-CAR. These differences still remained after adjusting for
      chronological age (CA), maturity and body size. In conclusion, the current study
      gives empirical support to the ecological and construct validity of this novel
      field test (T-CAR) as an indicator of match-related physical performance in young
      soccer players during pubertal years.

PMID- 27687492
TI  - Single-cell analysis reveals IGF-1 potentiation of inhibition of the TGF
      beta/Smad pathway of fibrosis in human keratocytes in vitro.
AB  - Corneal wound healing is often affected by TGF-beta-mediated fibrosis and scar
      formation. Guided fibrosis with IGF-1 and antifibrotic substances might maintain
      corneal transparency. Primary human corneal keratocytes under serum-free
      conditions were used as a model of corneal stromal wounding, with markers of
      corneal fibrosis and opacity studied under TGF-beta2 stimulation. Single-cell
      imaging flow cytometry was used to determine nuclearization of Smad3, and
      intracellular fluorescence intensity of Smad7 and the corneal crystallin aldehyde
      dehydrogenase 3A1. Extracellular matrix proteoglycans keratocan and biglycan were
      quantified using ELISAs. On the TGF-beta2 background, the keratocytes were
      treated with IGF-1, and suberoylanilidehydroxamic acid (SAHA) or halofuginone +/-
      IGF-1. IGF-1 alone decreased Smad3 nuclearization and increased aldehyde
      dehydrogenase 3A1 expression, with favorable extracellular matrix proteoglycan
      composition. SAHA induced higher Smad7 levels and inhibited translocation of
      Smad3 to the nucleus, also when combined with IGF-1. Immunofluorescence showed
      that myofibroblast transdifferentiation is attenuated and appearance of
      fibroblasts is favored by IGF-1 alone and in combination with the antifibrotic
      substances. The TGF-beta/Smad pathway of fibrosis and opacity was inhibited by
      IGF-1, and further with SAHA in particular, and with halofuginone. IGF-1 is thus
      a valid aid to antifibrotic treatment, with potential for effective and
      transparent corneal wound healing.

PMID- 27687494
TI  - The endocrine influence on the bone microenvironment in early breast cancer.
AB  - Multiple factors influence the survival of disseminated breast tumour cells
      (DTCs) in bone. Whereas gene signature studies have identified genes that predict
      a propensity of tumours to metastasise to bone, the bone environment is key in
      determining the fate of these tumour cells. Breast cancer cells locate to
      specific niches within the bone that support their survival, regulated by host
      factors within the bone microenvironment including bone cells, cells of the bone
      micro vasculature, immune cells and the extracellular matrix. Reproductive
      endocrine hormones that affect bone and clinical studies across the menopausal
      transition have provided comprehensive understanding of the changes in the bone
      microenvironment during this time. Menopause is characterized by a decrease in
      ovarian oestradiol and inhibins, with an increase in pituitary follicle
      stimulating hormone and this review will focus on the role of these three
      hormones in determining the fate of DTCs in bone. Both in vivo and clinical data
      suggest that premenopausal bone is a conducive environment for growth of breast
      cancer cells in bone. Adjuvant cancer treatment aims to reduce the risk of tumour
      recurrence by affecting DTCs. Drugs targeting the bone resorbing osteoclasts,
      such as bisphosphonates, have therefore been evaluated in this setting. Both
      preclinical and adjuvant clinical studies have shown that bisphosphonates'
      ability to decrease tumour growth in bone is influenced by the levels of
      endocrine hormones, with enhanced effects in a postmenopausal bone
      microenvironment. The challenge is to understand the molecular mechanisms behind
      this phenomenon and to evaluate if alternative adjuvant bone-targeted therapies
      may be effective in premenopausal women.

PMID- 27687495
TI  - Frequency-time coherence for all-optical sampling without optical pulse source.
AB  - Sampling is the first step to convert an analogue optical signal into a digital
      electrical signal. The latter can be further processed and analysed by well-known
      electrical signal processing methods. Optical pulse sources like mode-locked
      lasers are commonly incorporated for all-optical sampling, but have several
      drawbacks. A novel approach for a simple all-optical sampling is to utilise the
      frequency-time coherence of each signal. The method is based on only using two
      coupled modulators driven with an electrical sine wave. Since no optical source
      is required, a simple integration in appropriate platforms, such as Silicon
      Photonics might be possible. The presented method grants all-optical sampling
      with electrically tunable bandwidth, repetition rate and time shift.

PMID- 27687496
TI  - Anti TNF-alpha therapy for ulcerative colitis: current status and prospects for
      the future.
AB  - INTRODUCTION: Anti TNF-alpha agents have become a significant advance in the
      management of ulcerative colitis, proving to induce, with rapid onset, clinical
      and endoscopic remission. However, there is still a considerable unmet medical
      need in ulcerative colitis. Areas covered: The aim of this review was to
      summarize the patterns of use and the effectiveness of anti TNF-alpha in
      ulcerative colitis, highlighting their current position in treatment algorithms.
      Moreover, we set out a five-year view hypothesizing different treatment
      strategies. Expert commentary: The rapid onset of action and the effectiveness in
      inducing mucosal healing are the most important pros of anti TNF-alpha,
      supporting present and future use. Conversely, the relevant risk of loss of
      response and the safety profile have raised several concerns. In the future, the
      advent of different molecular targeting therapies can improve the management of
      UC patients, evolving to individually tailored strategies.

PMID- 27687497
TI  - Antagonistic roles of Drosophila Tctp and Brahma in chromatin remodelling and
      stabilizing repeated sequences.
AB  - Genome stability is essential for all organisms. Translationally controlled
      tumour protein (TCTP) is a conserved protein associated with cancers. TCTP is
      involved in multiple intracellular functions, but its role in transcription and
      genome stability is poorly understood. Here, we demonstrate new functions of
      Drosophila TCTP (Tctp) in transcription and the stability of repeated sequences
      (rDNA and pericentromeric heterochromatin). Tctp binds Brahma (Brm) chromatin
      remodeler to negatively modulate its activity. Tctp mutants show abnormally high
      levels of transcription in a large set of genes and transposons. These defects
      are ameliorated by brm mutations. Furthermore, Tctp promotes the stability of
      repeated sequences by opposing the Brm function. Additional regulation of
      pericentromeric heterochromatin by Tctp is mediated by su(var)3-9 transcriptional
      regulation. Altogether, Tctp regulates transcription and the stability of
      repeated sequences by antagonizing excess Brm activity. This study provides
      insights into broader nuclear TCTP functions for the maintenance of genome
      stability.

PMID- 27687498
TI  - A general solution for opening double-stranded DNA for isothermal amplification.
AB  - Nucleic acid amplification is the core technology of molecular biology and
      genetic engineering. Various isothermal amplification techniques have been
      developed as alternatives to polymerase chain reaction (PCR). However, most of
      these methods can only detect single stranded nucleic acid. Herein, we put
      forward a simple solution for opening double-stranded DNA for isothermal
      detection methods. The strategy employs recombination protein from E. coli (RecA)
      to form nucleoprotein complex with single-stranded DNA, which could scan double
      stranded template for homologous sites. Then, the nucleoprotein can invade the
      double-stranded template to form heteroduplex in the presence of ATP, resulting
      in the strand exchange. The ATP regeneration system could be eliminated by using
      high concentration of ATP, and the 3'-OH terminal of the invasion strand can be
      recognized by other DNA modifying enzymes such as DNA polymerase or DNA ligase.
      Moreover, dATP was found to be a better cofactor for RecA, which make the system
      more compatible to DNA polymerase. The method described here is a general
      solution to open dsDNA, serving as a platform to develop more isothermal nucleic
      acids detection methods for real DNA samples based on it.

PMID- 27687499
TI  - Impaired ADAMTS9 secretion: A potential mechanism for eye defects in Peters Plus
      Syndrome.
AB  - Peters Plus syndrome (PPS), a congenital disorder of glycosylation, results from
      recessive mutations affecting the glucosyltransferase B3GLCT, leading to
      congenital corneal opacity and diverse extra-ocular manifestations. Together with
      the fucosyltransferase POFUT2, B3GLCT adds Glucosebeta1-3Fucose disaccharide to a
      consensus sequence in thrombospondin type 1 repeats (TSRs) of several proteins.
      Which of these target proteins is functionally compromised in PPS is unknown. We
      report here that haploinsufficiency of murine Adamts9, encoding a secreted
      metalloproteinase with 15 TSRs, leads to congenital corneal opacity and Peters
      anomaly (persistent lens-cornea adhesion), which is a hallmark of PPS. Mass
      spectrometry of recombinant ADAMTS9 showed that 9 of 12 TSRs with the O
      fucosylation consensus sequence carried the Glucosebeta1-3Fucose disaccharide and
      B3GLCT knockdown reduced ADAMTS9 secretion in HEK293F cells. Together, the
      genetic and biochemical findings imply a dosage-dependent role for ADAMTS9 in
      ocular morphogenesis. Reduced secretion of ADAMTS9 in the absence of B3GLCT is
      proposed as a mechanism of Peters anomaly in PPS. The functional link between
      ADAMTS9 and B3GLCT established here also provides credence to their recently
      reported association with age-related macular degeneration.

PMID- 27687500
TI  - 'We saw she was in danger, but couldn't do anything': Missed opportunities and
      health worker disempowerment during birth care in rural Burkina Faso.
AB  - BACKGROUND: Facility-based births have been promoted as the main strategy to
      reduce maternal and neonatal death risks at global scale. To improve birth
      outcomes, it is critical that health facilities provide quality care. Using a
      framework to assess quality of care, this paper examines health workers'
      perceptions about access to facility birth; the effectiveness of the care
      provided and obstacles to quality birth care in a rural area of Burkina Faso.
      METHODS: A qualitative study was conducted in 2011 in the Banfora Region, Burkina
      Faso. Participant observations were carried out in four different health centres
      for a period of three months; more than 30 deliveries were observed. In-depth
      interviews were conducted with 12 frontline health workers providing birth care
      and with two staff of the local health district management team. Interview
      transcripts and field notes were analysed thematically. RESULTS: Health workers
      in this rural area of Burkina Faso provided birth care in a context of limited
      financial resources, insufficient personnel and poorly equipped facilities; the
      quality of the birth care provided was severely compromised. Health workers
      tended to place the responsibility for poor quality of care on infrastructural
      limitations and patient behaviour, while our observational data also identified
      missed opportunities that would not demand additional resources throughout the
      process of care like early initiation of breastfeeding and skin-to-skin contact
      after birth. Health workers felt disempowered, having limited abilities to
      prevent and treat birth complications, and resorted to alternative and
      potentially harmful strategies. CONCLUSIONS: We found poor quality of care at
      birth, missed opportunities, and health worker disempowerment in rural health
      facilities of Banfora, Burkina Faso. There is an urgent need to provide health
      workers with the necessary tools to prevent and handle birth complications, and
      to ensure that existing low cost life-saving interventions in maternal and new
      born health are appropriately used and integrated into the daily routines in
      maternity wards at all levels.

PMID- 27687501
TI  - CO2 fixation by anaerobic non-photosynthetic mixotrophy for improved carbon
      conversion.
AB  - Maximizing the conversion of biogenic carbon feedstocks into chemicals and fuels
      is essential for fermentation processes as feedstock costs and processing is
      commonly the greatest operating expense. Unfortunately, for most fermentations,
      over one-third of sugar carbon is lost to CO2 due to the decarboxylation of
      pyruvate to acetyl-CoA and limitations in the reducing power of the bio
      feedstock. Here we show that anaerobic, non-photosynthetic mixotrophy, defined as
      the concurrent utilization of organic (for example, sugars) and inorganic (for
      example, CO2) substrates in a single organism, can overcome these constraints to
      increase product yields and reduce overall CO2 emissions. As a proof-of-concept,
      Clostridium ljungdahlii was engineered to produce acetone and achieved a mass
      yield 138% of the previous theoretical maximum using a high cell density
      continuous fermentation process. In addition, when enough reductant (that is, H2)
      is provided, the fermentation emits no CO2. Finally, we show that mixotrophy is a
      general trait among acetogens.

PMID- 27687502
TI  - Can CuO nanoparticles lead to epigenetic regulation of antioxidant enzyme system?
AB  - Copper has been used from ancient time in various applications. Scientists have
      exploited its means of exposure and consequences to living organisms. The
      peculiar property of nanomaterials that is a high surface to volume ratio has
      increased the range of application in products. Copper oxide nanoparticles (CuO
      NPs) are widely used in industrial applications such as semiconductor devices,
      gas sensor, batteries, solar energy converter, microelectronics, heat transfer
      fluids and consumer products. In contrast, acute toxicity of CuO NPs has also
      been reported. Subsequently, human and environmental health may be at a high
      risk. Their frequent use can also contaminate ecosystems. Therefore, the toxicity
      of CuO NPs needs to be thoroughly understood. In this review, we have tried to
      discuss the recent facts and mechanism that have been explored for CuO NPs
      induced toxicity at a cellular, in vivo and ecotoxicological level. Accordingly,
      the main cause for induction of toxicity by CuO NPs is the generation of reactive
      oxygen species (ROS) followed by the mitochondrial destruction that leads to
      apoptosis via the intrinsic pathway or under the condition such as hypoxia cell
      on exposure to CuO NPs may commit to necrosis. Moreover, CuO NPs also result in
      activation of MAPK pathways, ERKs and JNK/SAPK thus play an important role in the
      activation of AP-1. Furthermore, CuO NPs also leads to up-regulation of p53 and
      caspase three genes. Therefore, careful measures are required to explore omic
      technology to understand the molecular mechanism of the deleterious effects
      caused by CuO NPs. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27687503
TI  - Candida vulvovaginitis: A store with a buttery and a show window.
AB  - Although being an utterly frequent, non-mortal, yet distressing disease, and
      despite good knowledge of the pathogenesis and the availability of specific and
      safe treatment, vulvovaginal Candida (VVC) infection remains one of the most
      enigmatic problems for both physicians and patients. Good treatment requires a
      proper diagnosis. Too many caregivers (and patients treating themselves) react
      too simple-minded on the symptoms of VVC and treat VVC where they see it on the
      vulva. In this opinion paper, we plea for a thorough examination of women with
      VVC, especially in those women who suffer from recurrent disease since a long
      time, sometimes decades, which necessitates intensive examination of the vaginal
      flora, as this is invariably the reservoir for relapses and recurrent vulvitis.
      Examination of such complicated cases requires experienced clinical judgement,
      expertise bedside phase contrast microscopy of fresh vaginal fluid, classical
      cultures on Sabouroud medium and, if still unresolved, repetitive cultures taken
      by the patient herself at moments of symptoms, and/or nuclear acid amplification
      techniques to detect Candida genes in the vaginal fluid. Even if only vulvitis is
      evident, thorough expert examination of vaginal fluid is obligatory to diagnose
      VVC.

PMID- 27687504
TI  - Letter to the editor submitted in response to "Sodium thiosulfate as a treatment
      for calciphylaxis: A case series".

PMID- 27687505
TI  - Naringin in Ganshuang Granule suppresses activation of hepatic stellate cells for
      anti-fibrosis effect by inhibition of mammalian target of rapamycin.
AB  - A previous study has demonstrated that Ganshuang granule (GSG) plays an anti
      fibrotic role partially by deactivation of hepatic stellate cells (HSCs). In HSCs
      activation, mammalian target of rapamycin (mTOR)-autophagy plays an important
      role. We attempted to investigate the role of mTOR-autophagy in anti-fibrotic
      effect of GSG. The cirrhotic mouse model was prepared to demonstrate the anti
      fibrosis effect of GSG. High performance liquid chromatography (HPLC) analyses
      were used to identify the active component of GSG. The primary mouse HSCs were
      isolated and naringin was added into activated HSCs to observe its anti-fibrotic
      effect. 3-methyladenine (3-MA) and Insulin-like growth factor-1 (IGF-1) was
      added, respectively, into fully activated HSCs to explore the role of autophagy
      and mTOR. GSG played an anti-fibrotic role through deactivation of HSCs in
      cirrhotic mouse model. The concentration of naringin was highest in GSG by HPLC
      analyses and naringin markedly suppressed HSCs activation in vitro, which
      suggested that naringin was the main active component of GSG. The deactivation of
      HSCs caused by naringin was not because of the autophagic activation but mTOR
      inhibition, which was supported by the following evidence: first, naringin
      induced autophagic activation, but when autophagy was blocked by 3-MA,
      deactivation of HSCs was not attenuated or reversed. Second, naringin inhibited
      mTOR pathway, meanwhile when mTOR was activated by IGF-1, deactivation of HSCs
      was reversed. In conclusion, we have demonstrated naringin in GSG suppressed
      activation of HSCs for anti-fibrosis effect by inhibition of mTOR, indicating a
      potential therapeutic application for liver cirrhosis.

PMID- 27687506
TI  - Alphantioxidant activity of Cynara scolymus L. and Cynara cardunculus L. extracts
      obtained by different extraction techniques.
AB  - Extracts of different parts (heads, bracts and stems) of Cynara cardunculus L.
      (cardoon) and Cynara scolymus L. (globe artichoke), obtained by two different
      extraction techniques (Ultrasound-Assisted Extraction (UAE) and classical
      extraction (CE)) were examined and compared for their total phenolic content
      (TPC) and their antioxidant activity. Moreover, infusions of the plant's parts
      were also analysed and compared to aforementioned samples. Results showed that
      cardoon's heads extract (obtained by Ultrasound-Assisted Extraction) displayed
      the highest TPC values (1.57 mg Gallic Acid Equivalents (GAE) g-1 fresh weight
      (fw)), the highest DPPH* scavenging activity (IC50; 0.91 mg ml-1) and the highest
      ABTS*+ radical scavenging capacity (2.08 mg Trolox Equivalents (TE) g-1 fw)
      compared to infusions and other extracts studied. Moreover, Ultrasound-Assisted
      Extraction technique proved to be more appropriate and effective for the
      extraction of antiradical and phenolic compounds.

PMID- 27687507
TI  - Oceanography promotes self-recruitment in a planktonic larval disperser.
AB  - The application of high-resolution genetic data has revealed that oceanographic
      connectivity in marine species with planktonic larvae can be surprisingly
      limited, even in the absence of major barriers to dispersal. Australia's southern
      coast represents a particularly interesting system for studying planktonic larval
      dispersal, as the hydrodynamic regime of the wide continental shelf has potential
      to facilitate onshore retention of larvae. We used a seascape genetics approach
      (the joint analysis of genetic data and oceanographic connectivity simulations)
      to assess population genetic structure and self-recruitment in a broadcast
      spawning marine gastropod that exists as a single meta-population throughout its
      temperate Australian range. Levels of self-recruitment were surprisingly high,
      and oceanographic connectivity simulations indicated that this was a result of
      low-velocity nearshore currents promoting the retention of planktonic larvae in
      the vicinity of natal sites. Even though the model applied here is comparatively
      simple and assumes that the dispersal of planktonic larvae is passive, we find
      that oceanography alone is sufficient to explain the high levels of genetic
      structure and self-recruitment. Our study contributes to growing evidence that
      sophisticated larval behaviour is not a prerequisite for larval retention in the
      nearshore region in planktonic-developing species.

PMID- 27687508
TI  - Sperm retrieval rate and pregnancy rate in infertile couples undergoing in-vitro
      fertilisation and testicular sperm extraction for non-obstructive azoospermia in
      Hong Kong.
AB  - OBJECTIVE: There are currently no local data on the sperm retrieval and pregnancy
      rates in in-vitro fertilisation and testicular sperm extraction cycles,
      especially with regard to the presence of genetic abnormalities. This study aimed
      to determine the sperm retrieval and pregnancy rates in infertile couples who
      underwent in-vitro fertilisation and testicular sperm extraction for non
      obstructive azoospermia. METHODS: This retrospective case series was conducted at
      a tertiary assisted reproduction unit in Hong Kong. Men with non-obstructive
      azoospermia who underwent in-vitro fertilisation and testicular sperm extraction
      between January 2001 and December 2013 were included. The main outcome measures
      were sperm retrieval and pregnancy rates. RESULTS: During the study period, 89
      men with non-obstructive azoospermia underwent in-vitro fertilisation and
      testicular sperm extraction. Sperm was successfully retrieved in 40 (44.9%) men.
      There was no statistically significant difference in the sperm retrieval rate of
      those with karyotypic abnormalities (2/5, 40.0% vs 28/61, 45.9%; P=1.000) and
      AZFc microdeletion (3/6, 50.0% vs 28/61, 45.9%; P=1.000) compared with those
      without. Sperms were successfully retrieved in patients who had mosaic
      Klinefelter syndrome (2/3, 66.7%) but not in the patient with non-mosaic
      Klinefelter syndrome. No sperms were found in men with AZFa or AZFb
      microdeletions. Pregnancy test was positive in 15 (16.9%) patients and the
      clinical pregnancy rate was 13.5% (12/89) per cycle. The clinical pregnancy rate
      per transfer was 34.3% (12/35). CONCLUSIONS: The sperm retrieval rate and
      clinical pregnancy rate per initiated cycle in men undergoing in-vitro
      fertilisation and testicular sperm extraction in our unit were 44.9% and 13.5%,
      respectively. No sperms could be retrieved in the presence of AZFa and AZFb
      microdeletions, but karyotype and AZFc microdeletion abnormalities otherwise did
      not predict the success of sperm retrieval in couples undergoing in-vitro
      fertilisation and testicular sperm extraction. Genetic tests are important prior
      to testicular sperm extraction for patient selection and genetic counselling.

PMID- 27687510
TI  - Systemic aspects of conjugal resilience in couples with a child facing cancer and
      marrow transplantation.
AB  - INTRODUCTION: The negative impact of paediatric cancer on parents is well known
      and is even greater when intensive treatments are used. This study aimed to
      describe how couples whose child has received a transplant for the treatment of
      leukaemia view conjugal resilience and to evaluate the role of we-ness as a
      precursor of conjugal adjustment. METHODS: Four parental couples were
      interviewed. Interviews were analysed in two ways: inductive thematic analysis
      and rating of verbal content with the We-ness Coding Scale. RESULTS: Participants
      report that conjugal resilience involves the identification of the couple as a
      team and cohesion in the couple. Being a team generates certain collaborative
      interactions that lead to conjugal resilience. A sense of we-ness in parents is
      associated with fluctuation in the frequency of themes. DISCUSSION: Participants'
      vision of conjugal resilience introduced novel themes. The sense of we-ness
      facilitates cohesion and the process of conjugal resilience.

PMID- 27687509
TI  - Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori
      infected human gastric epithelium.
AB  - BACKGROUND: Helicobacter pylori (HP) infection induces methylation silencing of
      specific genes in gastric epithelium. Various stimuli activate the nonselective
      cation channel TRPV4, which is expressed in gastric epithelium where it detects
      mechanical stimuli and promotes ATP release. As CpG islands in TRPV4 are
      methylated in HP-infected gastric epithelium, we evaluated HP infection-dependent
      changes in TRPV4 expression in gastric epithelium. MATERIALS AND METHODS: Human
      gastric biopsy samples, a human gastric cancer cell line (AGS), and a normal
      gastric epithelial cell line (GES-1) were used to detect TRPV4 mRNA and protein
      expression by RT-PCR and Western blotting, respectively. Ca2+ imaging was used to
      evaluate TRPV4 ion channel activity. TRPV4 methylation status was assessed by
      methylation-specific PCR (MSP). ATP release was measured by a luciferin
      luciferase assay. RESULTS: TRPV4 mRNA and protein were detected in human gastric
      biopsy samples and in GES-1 cells. MSP and demethylation assays showed TRPV4
      methylation silencing in AGS cells. HP coculture directly induced methylation
      silencing of TRPV4 in GES-1 cells. In human samples, HP infection was associated
      with TRPV4 methylation silencing that recovered after HP eradication in a time
      dependent manner. CONCLUSION: HP infection-dependent DNA methylation suppressed
      TRPV4 expression in human gastric epithelia, suggesting that TRPV4 methylation
      may be involved in HP-associated dyspepsia.

PMID- 27687511
TI  - Genetic diversity and population structure of Hyporhamphus sajori (Beloniformes:
      Hemiramphidae) inferred from mtDNA control region and msDNA markers.
AB  - This paper presents preliminary data on the genetic diversity and population
      structure of Hyporhamphus sajori by analysing a 510 bp sequence in the
      mitochondrial DNA (mtDNA) control region and eight polymorphic microsatellite DNA
      loci. The H. sajori individuals from different locations were indistinguishable
      from one another based on mtDNA variation, as demonstrated with a neighbour
      joining tree and minimum spanning network analysis. Low level of genetic
      diversity and the absence of population structure in H. sajori from the north
      west Pacific Ocean, combined with negative indices for neutral evolution in these
      populations, suggest that H. sajori underwent a population expansion after a
      recent bottleneck. The Structure analysis, discriminant analysis of principal
      components (DAPC) and the pair-wise PhiST values after Bonferroni correction
      using eight microsatellite loci provided no clear inference on the genetic
      differentiation and thus no evidence of population structure of H. sajori. The
      genetic connectivity among locations might be due to fairly high gene flow via
      transport of eggs and larvae by the Kuroshio and Tsushima warm current. This
      study revealed low levels of genetic diversity and suggested high level of
      contemporary gene flow among populations of H. sajori in the East (Japan) Sea and
      the Pacific Ocean.

PMID- 27687513
TI  - Authors' reply to Ramachandran.

PMID- 27687512
TI  - Cadmium induces oxidative stress and apoptosis in lung epithelial cells.
AB  - Cadmium (Cd) is one of the well-known highly toxic environmental and industrial
      pollutants. Cd first accumulates in the nucleus and later interacts with zinc
      finger proteins of antiapoptotic genes and inhibit the binding of transcriptional
      factors and transcription. However, the role of Cd in oxidative stress and
      apoptosis is less understood. Hence, the present study was undertaken to unveil
      the mechanism of action. A549 cells were treated with or without Cd and cell
      viability was measured by MTT assay. Treatment of cells with Cd shows reduced
      viability in a dose-dependent manner with IC50 of 45 MUM concentration. Cd
      significantly induces the reactive oxygen species (ROS), lipid peroxidation
      followed by membrane damage with the leakage of lactate dehydrogenase (LDH).
      Cells with continuous exposure of Cd deplete the antioxidant super oxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Further, analysis of
      the expression of genes involved in apoptosis show that both the extrinsic and
      intrinsic apoptotic pathways were involved. Death receptor marker tumor necrosis
      factor-alpha (TNF-alpha), executor caspase-8 and pro-apoptotic gene (Bax) were
      induced, while antiapoptotic gene (Bcl-2) was decreased in Cd-treated cells.
      Fluorescence-activated cell sorting (FACS) analysis further confirms the
      induction of apoptosis in Cd-treated A549 cells.

PMID- 27687514
TI  - Anatomic Patterns of Renal Arterial Sympathetic Innervation: New Aspects for
      Renal Denervation.
AB  - AIMS: Initial studies of catheter-based renal arterial sympathetic denervation to
      lower blood pressure in resistant hypertensive patients renewed interest in the
      sympathetic nervous system's role in the pathogenesis of hypertension. However,
      the SYMPLICITY HTN-3 study failed to meet its prespecified blood pressure
      lowering efficacy endpoint. To date, only a limited number of studies have
      described the microanatomy of renal nerves, of which, only two involve humans.
      METHODS AND RESULTS: Renal arteries were harvested from 15 cadavers from the
      Klinikum Osnabruck and Schuchtermann Klinik, Bad Rothenfelde. Each artery was
      divided longitudinally in equal thirds (proximal, middle, and distal), with each
      section then divided into equal superior, inferior, anterior, and posterior
      quadrants, which were then stained. Segments containing no renal nerves were
      given a score value = 0, 1-2 nerves with diameter <300 um a score = 1; 3-4 nerves
      or nerve diameter 300-599 um a score = 2, and >4 nerves or nerve diameter >=600
      um a score = 3. A total of 22 renal arteries (9 right-sided, 13 left-sided) were
      suitable for examination. Overall, 691 sections of 5 mm thickness were prepared.
      Right renal arteries had significantly higher mean innervation grade (1.56 +/-
      0.85) compared to left renal arteries (1.09 +/- 0.87) (P < 0.001). Medial (1.30
      +/- 0.59) and distal (1.39 +/- 0.62) innervation was higher than the proximal
      (1.17 +/- 0.55) segments (p < 0.001). When divided in quadrants, the anterior
      (1.52 +/- 0.96) and superior (1.71 +/- 0.89) segments were more innervated
      compared to posterior (0.96 +/- 0.72) and inferior (0.90 +/- 0.68) segments (P <
      0.001). CONCLUSIONS: That the right renal artery has significantly higher
      innervation scores than the left. The anterior and superior quadrants of the
      renal arteries scored higher in innervation than the posterior and inferior
      quadrants did. The distal third of the renal arteries are more innervated than
      the more proximal segments. These findings warrant further evaluation of the
      spatial innervation patterns of the renal artery in order to understand how it
      may enhance catheter-based renal arterial denervation procedural strategy and
      outcomes. CONDENSED ABSTRACT: The SYMPLICITY HTN-3 study dealt a blow to the idea
      of the catheter-based renal arterial sympathetic denervation. We investigated the
      location and patterns of periarterial renal nerves in cadaveric human renal
      arteries. To quantify the density of the renal nerves we created a novel
      innervation score. On average the right renal arteries were significantly more
      densely innervated than the left renal arteries, the anterior and superior
      segments were significantly more innervated compared to the posterior and
      inferior segments, absolute innervation scores in the proximal third of the left
      or right renal arteries were always lower when compared to distal segments. These
      findings may enhance catheter-based renal arterial denervation procedural
      strategy and outcomes.

PMID- 27687515
TI  - Psychological distress and coping in nasopharyngeal cancer: an explorative study
      in Western Europe.
AB  - Nasopharyngeal carcinoma (NPC) is the head and neck cancer with the greatest
      impact on patients' quality of life. The aim of this explorative study is to
      investigate the psychological distress, coping strategies and quality of life of
      NPC patients in the post-treatment observation period. Twenty-one patients
      disease-free for at least two years were assessed with a medical and a psycho
      oncological evaluation. Clinically relevant depressive symptoms (CRD) were
      present in 23.8% of patients and 33.3% reported clinically relevant anxiety
      symptoms (CRA). Patients with CRD and CRA showed a significantly higher score in
      the use of hopelessness/helplessness and anxious preoccupation coping strategies
      and a worse quality of life. Even in the post-treatment period, about a quarter
      of patients showed CRD and CRA. Results showed that patients with high anxiety or
      depressive symptoms seem to use dysfunctional coping strategies, such as
      hopelessness and anxious preoccupation, more than patients with lower levels of
      anxiety and depression. The use of these styles of coping thus seems to be
      associated to a higher presence of CRA or CRD symptomatology and to a worse
      quality of life.

PMID- 27687516
TI  - Productivity, Rank, and Returns in Polygamy.
AB  - This study sheds light on the development of family structures in a polygamous
      context with a particular emphasis on wife order, and offers an explanation for
      the association between outcomes of children and the status of their mothers
      among wives based on observable maternal characteristics. In a simple framework,
      I propose that selection into rank among wives with respect to female
      productivity takes place: highly productive women are more strongly demanded in
      the marriage market than less productive women, giving them a higher chance of
      becoming first wives. Furthermore, productivity is positively associated with a
      wife's bargained share of family income to be spent on consumption and investment
      for herself and her offspring because of greater contributions to family income
      and larger outside options. The findings are empirically supported by a positive
      relationship between indicators of female productivity and women's levels of
      seniority among wives, and by a concise replication of existing evidence relating
      wife order to children's educational outcomes in household survey data from rural
      Ethiopia.

PMID- 27687517
TI  - Number of evaluated lymph nodes and positive lymph nodes, lymph node ratio, and
      log odds evaluation in early-stage pancreatic ductal adenocarcinoma: numerology
      or valid indicators of patient outcome?
AB  - BACKGROUND: We evaluated the prognostic significance and universal validity of
      the total number of evaluated lymph nodes (ELN), number of positive lymph nodes
      (PLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in a
      relatively large and homogenous cohort of surgically treated pancreatic ductal
      adenocarcinoma (PDAC) patients. METHODS: Prospectively accrued data were
      retrospectively analyzed for 282 PDAC patients who had pancreaticoduodenectomy
      (PD) at our institution. Long-term survival was analyzed according to the ELN,
      PLN, LNR, and LODDS. RESULTS: Of these patients, 168 patients (59.5 %) had LN
      metastasis (N1). Mean ELN and PLN were 13.5 and 1.6, respectively. LN positivity
      correlated with a greater number of evaluated lymph nodes; positive lymph nodes
      were identified in 61.4 % of the patients with ELN >= 13 compared with 44.9 % of
      the patients with ELN < 13 (p = 0.014). Median overall survival (OS) and 5-year
      OS rate were higher in N0 than in N1 patients, 22.4 vs. 18.7 months and 35 vs. 11
      %, respectively (p = 0.008). Mean LNR was 0.12; 91 patients (54.1 %) had LNR <
      0.3. Among the N1 patients, median OS was comparable in those with LNR >= 0.3 vs.
      LNR < 0.3 (16.7 vs. 14.1 months, p = 0.950). Neither LODDS nor various ELN and
      PLN cutoff values provided more discriminative information within the group of N1
      patients. CONCLUSIONS: Our data confirms that lymph node positivity strongly
      reflects PDAC biology and thus patient outcome. While a higher number of
      evaluated lymph nodes may provide a more accurate nodal staging, it does not have
      any prognostic value among N1 patients. Similarly, PLN, LNR, and LODDS had
      limited prognostic relevance.

PMID- 27687518
TI  - Quantification of gamma-aminobutyric acid (GABA) in 1 H MRS volumes composed
      heterogeneously of grey and white matter.
AB  - The quantification of gamma-aminobutyric acid (GABA) concentration using
      localised MRS suffers from partial volume effects related to differences in the
      intrinsic concentration of GABA in grey (GM) and white (WM) matter. These
      differences can be represented as a ratio between intrinsic GABA in GM and WM: rM
      . Individual differences in GM tissue volume can therefore potentially drive
      apparent concentration differences. Here, a quantification method that corrects
      for these effects is formulated and empirically validated. Quantification using
      tissue water as an internal concentration reference has been described
      previously. Partial volume effects attributed to rM can be accounted for by
      incorporating into this established method an additional multiplicative
      correction factor based on measured or literature values of rM weighted by the
      proportion of GM and WM within tissue-segmented MRS volumes. Simulations were
      performed to test the sensitivity of this correction using different assumptions
      of rM taken from previous studies. The tissue correction method was then
      validated by applying it to an independent dataset of in vivo GABA measurements
      using an empirically measured value of rM . It was shown that incorrect
      assumptions of rM can lead to overcorrection and inflation of GABA concentration
      measurements quantified in volumes composed predominantly of WM. For the
      independent dataset, GABA concentration was linearly related to GM tissue volume
      when only the water signal was corrected for partial volume effects. Performing a
      full correction that additionally accounts for partial volume effects ascribed to
      rM successfully removed this dependence. With an appropriate assumption of the
      ratio of intrinsic GABA concentration in GM and WM, GABA measurements can be
      corrected for partial volume effects, potentially leading to a reduction in
      between-participant variance, increased power in statistical tests and better
      discriminability of true effects.

PMID- 27687519
TI  - Cardiovascular benefits from ancient grain bread consumption: findings from a
      double-blinded randomized crossover intervention trial.
AB  - Ancient grain varieties have been shown to have some beneficial effects on
      health. Forty-five clinically healthy subjects were included in a randomized,
      double-blinded crossover trial aimed at evaluating the effect of a replacement
      diet with bread derived from ancient grain varieties versus modern grain variety
      on cardiovascular risk profile. After 8 weeks of intervention, consumption of
      bread obtained by the ancient varieties showed a significant amelioration of
      various cardiovascular parameters. Indeed, the ancient varieties were shown to
      result in a significant reduction of total cholesterol, low-density lipoprotein
      (LDL)-cholesterol and blood glucose, whereas no significant differences during
      the phase with the modern variety were reported. Moreover, a significant increase
      in circulating endothelial progenitor cells were reported after the consumption
      of products made from the ancient "Verna" variety. The present results suggest
      that a dietary consumption of bread obtained from ancient grain varieties was
      effective in reducing cardiovascular risk factors.

PMID- 27687520
TI  - Polyester hydrolysis is enhanced by a truncated esterase: Less is more.
AB  - An esterase from Clostridium botulinum (Cbotu_EstA) previously reported to
      hydrolyze the biodegradable polyester poly(butylene adipate-co-terephthalate) was
      redesigned to improve the hydrolysis of synthetic polyesters. Increased activity
      was indeed observed for del71Cbotu_EstA variant, which performed activity on the
      widespread polyester polyethylene terephthalate, which was not able to be
      attacked by the wild-type enzyme Cbotu_EstA. Analysis of the 3D structure of the
      enzyme showed that removing 71 residues at the N-terminus of the enzyme exposed a
      hydrophobic patch on the surface and improved sorption of hydrophobic polyesters
      concomitantly facilitating the access of the polymer to the active site. These
      results show a new route for enhancing enzyme activity for hydrolysis and
      modification of polyesters.

PMID- 27687521
TI  - Tongue Strength is Associated with Grip Strength and Nutritional Status in Older
      Adult Inpatients of a Rehabilitation Hospital.
AB  - The aim of this cross-sectional study was to investigate whether tongue strength
      observed in older adult inpatients of a rehabilitation hospital is associated
      with muscle function, nutritional status, and dysphagia. A total of 174 older
      adult inpatients aged 65 years and older in rehabilitation (64 men, 110 women;
      median age, 84 years; interquartile range, 80-89 years) who were suspected of
      having reduced tongue strength due to sarcopenia were included in this study.
      Isometric tongue strength was measured using a device fitted with a disposable
      oral balloon probe. We evaluated age, muscle function as assessed by the Barthel
      index and grip strength, nutritional status as measured by the Mini Nutritional
      Assessment-short form (MNA-SF), body mass index, serum albumin, controlling
      nutritional status, and calf circumference and arm muscle area to assess muscle
      mass. In addition, the functional oral intake scale (FOIS) was used as an index
      of dysphagia. Multivariate linear regression analysis revealed that isometric
      tongue strength was independently associated with grip strength (coefficient =
      0.33, 95 % confidence interval (CI) 0.12-0.54, p = 0.002), MNA-SF (coefficient =
      0.74, 95 % CI 0.12-1.35, p = 0.019), and FOIS (coefficient = 0.02, 95 % CI 0.00
      0.15, p = 0.047). To maintain and improve tongue strength in association with
      sarcopenic dysphagia, exercise therapy and nutritional therapy interventions, as
      well as direct interventions to address tongue strength, may be effective in
      dysphagia rehabilitation in older adult inpatients.

PMID- 27687522
TI  - Prevalence of Tracheotomy and Percutaneous Endoscopic Gastrostomy in Patients
      with Guillain-Barre Syndrome.
AB  - Some patients with Guillain-Barre syndrome require respiratory management by
      tracheotomy and/or nutritional management by tube feeding; however, few studies
      have reported the follow-up course in these patients. The objective of this study
      was to investigate the follow-up course of tracheotomy and gastrostomy in
      patients with Guillain-Barre syndrome. The study subjects were 50 patients with
      Guillain-Barre syndrome (25 males, 25 females; mean age, 51.1 +/- 18.7 years) who
      were admitted to the Hiroshima City Rehabilitation Hospital during the period
      from April 2008 to December 2015. We retrospectively reviewed the medical records
      to determine the presence or absence of tracheotomy and/or feeding tube, and the
      timing of withdrawal from these treatments. During the acute phase, 15 patients
      underwent tracheotomy and 14 underwent tube feeding management. A tracheotomy
      tube was inserted for 110 days or longer in five patients, and four of these five
      patients also had a gastrostomy tube inserted. Among the 14 patients in the tube
      feeding group, seven underwent nasal feeding and seven underwent percutaneous
      endoscopic gastrostomy. All patients had the nasal tube removed (mean duration of
      nasal tube placement, 62.1 +/- 46.5 days); however, the gastrostomy tube could
      not be removed in two patients. Our findings indicate that patients in the acute
      phase of Guillain-Barre syndrome carry a relevant risk of long-term tube feeding
      and prolonged need of an artificial airway.

PMID- 27687523
TI  - Second malignant neoplasm following childhood cancer: A nested case-control study
      of a recent cohort (1987-2004) from the Childhood Cancer Registry of the Rhone
      Alpes region in France.
AB  - From a population-based cohort of cases of first cancers diagnosed between 1987
      and 2004, before the patient's age of 15 years, the authors conducted a nested
      case-control study, matching 64 patients who experienced a second malignant
      neoplasm (SMN) with 190 controls. SMNs comprised 10 leukemia or myelodysplastic
      syndromes, 5 lymphomas induced by Epstein-Barr virus after allograft, and 49
      solid tumors, including mainly 25 carcinomas (17 of the thyroid), 9 bone
      sarcomas, and 7 central nervous system (CNS) tumors. The median latency
      occurrence was 6.5 years, and that of thyroid carcinomas induced by 12 Gy
      fractioned total body irradiation (TBI) was 7.6 years. The relative risk (RR) of
      an SMN was increased by genetic and family factors and increased 17 to 69 times
      according to the dose of radiotherapy administered in the region for the first
      cancer. Age younger than 4 years at the time of radiotherapy increased the risk
      of SMN. Chemotherapy adjusted according to the dose of radiotherapy administered
      in the field yielded a greater RR of an SMN only for cumulative doses exceeding 2
      g/m2 of epipodophyllotoxin but not for alkylating agents or platinum compounds.
      The RR of secondary leukemia increased 10-fold following high doses of
      epipodophyllotoxin >2 g/m2 but was not affected by alkylating agents or
      anthracyclines. The crude RR of a solid SMN developing after radiotherapy was
      very high at 18 and reached 90.7 for thyroid carcinoma after TBI, whereas the
      authors observed no increased risk associated with chemotherapy. These results
      confirm the risk of secondary leukemia after epipodophyllotoxin and of solid
      tumor after radiotherapy.

PMID- 27687524
TI  - Variations in within-group inter-individual distances between birth- and non
      birth seasons in wild female patas monkeys.
AB  - Individual spatial positioning plays an important role in mediating the costs and
      benefits of group living, and thus shapes different aspects of animal social
      systems including group structure and cohesiveness. I aimed to quantify variation
      in individual spacing behavior and its correlates in a group of wild patas
      monkeys (Erythrocebus patas) living in north Cameroon. I collected data on inter
      individual distances during group scans when following subject females.
      Individuals had longer inter-individual distances during the non-birth season
      than during the birth season. Dominance relationships had little effect on inter
      individual distances between females during both the non-birth and birth seasons.
      The results suggest that group cohesion was higher during the birth season than
      the non-birth season. Thus I conclude that higher group cohesion during the birth
      season may reduce the predation risk of infants.

PMID- 27687525
TI  - Microglia energy metabolism in metabolic disorder.
AB  - Microglia are the resident macrophages of the CNS, and are in charge of
      maintaining a healthy microenvironment to ensure neuronal survival. Microglia
      carry out a non-stop patrol of the CNS, make contact with neurons and look for
      abnormalities, all of which requires a vast amount of energy. This non-signaling
      energy demand increases after activation by pathogens, neuronal damage or other
      kinds of stimulation. Of the three major energy substrates - glucose, fatty acids
      and glutamine - glucose is crucial for microglia survival and several glucose
      transporters are expressed to supply sufficient glucose influx. Fatty acids are
      another source of energy for microglia and have also been shown to strongly
      influence microglial immune activity. Glutamine, although possibly suitable for
      use as an energy substrate by microglia, has been shown to have neurotoxic
      effects when overloaded. Microglial fuel metabolism might be associated with
      microglial reactivity under different pathophysiological conditions and a
      microglial fuel switch may thus be the underlying cause of hypothalamic
      dysregulation, which is associated with obesity.

PMID- 27687526
TI  - Assessment of patient safety culture: what tools for medical students?
AB  - BACKGROUND: The assessment of patient safety culture refers mainly to surveys
      exploring the perceptions of health professionals in hospitals. These surveys
      have less relevance when considering the assessment of the patient safety culture
      of medical students, especially at university or medical school. They are indeed
      not fully integrated in care units and constitute a heterogeneous population.
      This work aimed to find appropriate assessment tools of the patient safety
      culture of medical students. METHODS: Systematic review of the literature.
      Surveys related to a care unit were excluded. A typology of the patient safety
      culture of medical students was built from the included surveys. RESULTS:
      Eighteen surveys were included. In our typology of patient safety culture of
      medical students (15 dimensions), the number of dimensions explored by survey (n)
      ranged from 1 to 12, with 6 "specialized" tools (n <= 4) and 12 "global" tools (N
      >= 5). These surveys have explored: knowledge about patient safety,
      acknowledgment of the inevitability of human error, the lack of skills as the
      main source of errors, the errors reporting systems, disclosure of medical errors
      to others health professionals or patients, teamwork and patient involvement to
      improve safety in care. CONCLUSIONS: We recommend using Wetzel's survey for
      making an overall assessment of the patient safety culture of medical students at
      university. In a specific purpose-e.g. to assess an educational program on
      medical error disclosure-the authors recommend to determine which dimensions of
      patient safety will be taught, to select the best assessment tool. Learning on
      patient safety should however be considered beyond the university. International
      translations of tools are required to create databases allowing comparative
      studies.

PMID- 27687527
TI  - Evaluation of the brain-penetrant microtubule-stabilizing agent, dictyostatin, in
      the PS19 tau transgenic mouse model of tauopathy.
AB  - Neurodegenerative disorders referred to as tauopathies, which includes
      Alzheimer's disease (AD), are characterized by insoluble deposits of the tau
      protein within neuron cell bodies and dendritic processes in the brain. Tau is
      normally associated with microtubules (MTs) in axons, where it provides MT
      stabilization and may modulate axonal transport. However, tau becomes
      hyperphosphorylated and dissociates from MTs in tauopathies, with evidence of
      reduced MT stability and defective axonal transport. This has led to the
      hypothesis that MT-stabilizing drugs may have potential for the treatment of
      tauopathies. Prior studies demonstrated that the brain-penetrant MT-stabilizing
      drug, epothilone D, had salutary effects in transgenic (Tg) mouse models of
      tauopathy, improving MT density and axonal transport, while reducing axonal
      dystrophy. Moreover, epothilone D enhanced cognitive performance and decreased
      hippocampal neuron loss, with evidence of reduced tau pathology. To date,
      epothilone D has been the only non-peptide small molecule MT-stabilizing agent to
      be evaluated in Tg tau mice. Herein, we demonstrate the efficacy of another small
      molecule brain-penetrant MT-stabilizing agent, dictyostatin, in the PS19 tau Tg
      mouse model. Although dictyostatin was poorly tolerated at once-weekly doses of 1
      mg/kg or 0.3 mg/kg, likely due to gastrointestinal (GI) complications, a
      dictyostatin dose of 0.1 mg/kg was better tolerated, such that the majority of 6
      month old PS19 mice, which harbor a moderate level of brain tau pathology,
      completed a 3-month dosing study without evidence of significant body weight
      loss. Importantly, as previously observed with epothilone D, the dictyostatin
      treated PS19 mice displayed improved MT density and reduced axonal dystrophy,
      with a reduction of tau pathology and a trend toward increased hippocampal neuron
      survival relative to vehicle-treated PS19 mice. Thus, despite evidence of dose
      limiting peripheral side effects, the observed positive brain outcomes in
      dictyostatin-treated aged PS19 mice reinforces the concept that MT-stabilizing
      compounds have significant potential for the treatment of tauopathies.

PMID- 27687528
TI  - Respiratory health effects of occupational exposure to charcoal dust in Namibia.
AB  - BACKGROUND: Charcoal processing activities can increase the risk of adverse
      respiratory outcomes. OBJECTIVE: To determine dose-response relationships between
      occupational exposure to charcoal dust, respiratory symptoms and lung function
      among charcoal-processing workers in Namibia. METHODS: A cross-sectional study
      was conducted with 307 workers from charcoal factories in Namibia. All
      respondents completed interviewer-administered questionnaires. Spirometry was
      performed, ambient and respirable dust levels were assessed in different work
      sections. Multiple logistic regression analysis estimated the overall effect of
      charcoal dust exposure on respiratory outcomes, while linear regression estimated
      the exposure-related effect on lung function. Workers were stratified according
      to cumulative dust exposure category. RESULTS: Exposure to respirable charcoal
      dust levels was above occupational exposure limits in most sectors, with packing
      and weighing having the highest dust exposure levels (median 27.7 mg/m3, range:
      0.2-33.0 for the 8-h time-weighted average). The high cumulative dust exposure
      category was significantly associated with usual cough (OR: 2.1; 95% CI: 1.1
      4.0), usual phlegm (OR: 2.1; 95% CI: 1.1-4.1), episodes of phlegm and cough (OR:
      2.8; 95% CI: 1.1-6.1), and shortness of breath. A non-statistically significant
      lower adjusted mean-predicted % FEV1 was observed (98.1% for male and 95.5% for
      female) among workers with greater exposure. CONCLUSIONS: Charcoal dust levels
      exceeded the US OSHA recommended limit of 3.5 mg/m3 for carbon-black-containing
      material and study participants presented with exposure-related adverse
      respiratory outcomes in a dose-response manner. Our findings suggest that the
      Namibian Ministry of Labour introduce stronger enforcement strategies of existing
      national health and safety regulations within the industry.

PMID- 27687529
TI  - Birth Outcomes Among U.S. Women With Hearing Loss.
AB  - INTRODUCTION: The purpose of this study is to estimate the national occurrence of
      deliveries in women with hearing loss and to compare their birth outcomes to
      women without hearing loss. METHODS: This study examined the 2008-2011 Nationwide
      Inpatient Sample of the Healthcare Cost and Utilization Project in 2015 to
      compare birth outcomes in women with hearing loss and without. Birth outcomes
      included preterm birth and low birth weight. Multivariate regression analyses
      compared birth outcomes between women with and without hearing loss, controlling
      for maternal age, racial and ethnic identity, type of health insurance,
      comorbidity, region of hospital, location and teaching status of the hospital,
      ownership of the hospital, and median household income for mother's ZIP code.
      RESULTS: Of an estimated 17.9 million deliveries, 10,462 occurred in women with
      hearing loss. In adjusted regression analyses controlling for demographic
      characteristics, women with hearing loss were significantly more likely than
      those without hearing loss to have preterm birth (OR=1.28, 95% CI=1.08, 1.52,
      p<0.001) and low birth weight (OR=1.43, 95% CI=1.09, 1.90, p<0.05). CONCLUSIONS:
      This study provides a first examination of the pregnancy outcomes among women
      with hearing loss in the U.S. This analysis demonstrates significant disparities
      in birth outcomes between women with and without hearing loss. Understanding and
      addressing the causes of these disparities is critical to improving pregnancy
      outcomes among women with hearing loss.

PMID- 27687530
TI  - Wip 1 inhibits intestinal inflammation in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's
      disease (CD), is a chronically intestinal autoimmune disease, the pathological
      mechanisms of which are not very clear. Wild type p-53 induced phosphatase 1
      (Wip1), a serine/threonine protein phosphatase, has been reported to negatively
      regulate the inflammation in sepsis. However, the role of Wip1 in IBD is not very
      clear. Therefore, colonic tissues and peripheral blood from patients with IBD and
      healthy controls were collected to analyzed mRNA and protein expression of Wip1
      using the method of qPCR and immunohistochemistry. Immune cells of neutrophils,
      CD4+ T cells, CD8+ T cells, B cells, monocytes and intestinal epithelial cells
      were isolated to analyze Wip1 expression by means of qPCR. Expression of Wip 1
      was analyzed after the cells were stimulated by various of cytokines. DSS-colitis
      model was induced on the wild type (WT) and Wip 1 knock out (Wip1-/-) mice, and
      cytokines expression were analyzed in intestinal lamina propria from WT and Wip1
      /- mice. Neutrophil specific markers were examined in intestinal lamina propria
      from WT and Wip1-/- mice. Moreover, neutrophils were isolated from bone marrow of
      WT and Wip1-/- mice to examine neutrophil migration with or without inhibitors of
      signaling pathway in vitro. The expression of Wip 1 mRNA and protein were found
      to be significantly decreased in patients with active IBD compared with healthy
      controls. And Wip 1 was mainly expressed on neutrophils from peripheral blood and
      colonic tissues. Moreover, expression of Wip1 was significantly decreased on
      neutrophils after the stimulation of TNF-alpha and IFN-gamma. Wip1-/- mice were
      more susceptible to DSS induced colitis compared to WT mice, and expressed more
      pro-inflammatory cytokines (e.g. TNF-alpha, IFN-gamma, IL-17A, etc). Moreover,
      expression of neutrophil specific markers (e.g. Ly6G, CD11b, elastase, etc) was
      also increased in Wip1-/- mice. The migration of neutrophils from the bone marrow
      of Wip1 mice was marked increased, which was mediated by MAPK-P38 signaling
      pathway. Wip1 plays an importantly protective role in the pathogenesis of IBD.
      Therefore, Wip1 may be used a new targets in the treatment for IBD in the future.

PMID- 27687531
TI  - Long-term outcomes of the Kropp and Salle urethral lengthening bladder neck
      reconstruction procedures.
AB  - INTRODUCTION: The Kropp and Salle procedures have shown good short-term outcomes
      for managing neuropathic urinary incontinence. However, few studies have assessed
      their long-term results. OBJECTIVE: This study aimed to evaluate the long-term
      outcomes of Kropp and Salle procedures, including: dryness, secondary
      interventions for incontinence or complications, upper urinary tract changes, and
      use of urethral catheterizations. STUDY DESIGN: Consecutive patients undergoing
      Kropp and Salle procedures at the present institution (1983-2012) were
      retrospectively reviewed. Patients with <1-year follow-up or prior bladder neck
      (BN) continence procedures were excluded. Data were collected on postoperative
      dryness per urethra at 4-hourly and 3-hourly intervals, secondary interventions,
      lab tests, and imaging. Non-parametric tests were used for statistical analysis.
      RESULTS: Thirty-eight patients had Kropp (K: 30 boys) and 12 had Salle procedures
      (S: 8 boys). Patients underwent surgery at similar median ages (K: 7.4 vs S: 8.7
      years old, P = 0.51) and had similar median follow-up (6.9 vs 10.3 years, P =
      0.10). Most patients had myelomeningocele, a prior/concomitant bladder
      augmentation (K: 73.7%, S: 58.3%) and catheterizable channel (K: 81.6%, S:
      50.0%). Differences in all outcomes between Kropp and Salle procedures were
      statistically non-significant. The majority of patients did not have additional
      BN procedures for dryness (K: 84.2%, S: 66.7%). Of this group, K: 81.3% and S:
      75.0% were dry for >=4 h, K: 93.8% and S: 87.5% were dry for >=3 h between
      catheterizations (Table). Of the minority of patients who underwent additional BN
      procedures for dryness (K: 15.8%, S: 33.3%), most achieved dryness for >=4 h (K:
      66.7%, S: 100%) and >=3 h (100% for both). Among patients without an initial
      catheterizable channel, 57.1% had one subsequently created after a Kropp
      procedure, and 33.3% after a Salle. Among patients without bladder augmentation,
      approximately half underwent delayed augmentation (K: 50.0%, S: 40.0%).
      Ultimately, most patients required a secondary intervention under anesthesia for
      incontinence or complications (K: 79.0%, S: 66.7%). Few patients developed
      worsening hydronephrosis, vesicoureteral reflux or renal function (K: 2.6%, S:
      0.0%). At the end of follow-up, few patients catheterized per urethra (K: 10.5%,
      S: 33.3%). DISCUSSION: This was a retrospective study without urodynamic data.
      Originating from a tertiary center, the results may not apply to other clinical
      settings. CONCLUSIONS: At the present institution the Kropp and Salle procedures
      attained similar dryness in 75-81% at 4-hourly intervals and 88-94% at 3-hourly
      intervals without additional BN procedures. Few patients required subsequent BN
      procedures to achieve dryness. However, the overall need for secondary procedures
      during long-term follow-up was high for both procedures.

PMID- 27687532
TI  - Management of undescended testes: European Association of Urology/European
      Society for Paediatric Urology Guidelines.
AB  - CONTEXT: Undescended testis is the most common endocrinological disease in the
      male newborn period. Incidence varies between 1.0% and 4.6% in full-term
      neonates, with rates as high as 45% in preterm neonates. Failure or delay of
      treatment can result in reduced fertility and/or increased testicular cancer risk
      in adulthood. OBJECTIVE: To provide recommendations for the diagnosis and
      treatment of boys with undescended testes which reduce the risk of impaired
      fertility and testicular cancer in adulthood. EVIDENCE ACQUISITION: Embase and
      Pubmed were searched for all relevant publications, from 1990 to 2015 limited to
      English language. Data were narratively synthesized in light of methodological
      and clinical heterogeneity. The risk of bias of each included study was assessed.
      EVIDENCE SYNTHESIS: There is consensus that early treatment, by 18 months at the
      latest, for undescended testes is mandatory to avoid possible sequelae regarding
      fertility potential and cancer risk. The current standard therapy is orchidopexy,
      while hormonal therapy is still under debate. However, in some individuals the
      successful scrotal placement of previously undescended testes may not prevent
      potential negative long-term outcomes regarding fertility and testicular
      malignancy. CONCLUSIONS: There is good evidence for early placement of
      undescended testes in the scrotal position to prevent potential impairment of
      fertility and reduce the risk of testicular malignancy. No consensus exists on
      the various forms of hormonal treatment, which are assessed on an individual
      basis.

PMID- 27687533
TI  - Robotic-assisted laparoscopic bladder augmentation in the pediatric patient.
AB  - INTRODUCTION: Bladder augmentation is a common surgical intervention for
      neuropathic bladder dysfunction, and has conventionally been an open procedure.
      We present a robotic ileocystoplasty to demonstrate the feasibility of an
      entirely intracorporeal approach in a pediatric patient. METHODS: The patient was
      a 6 year old (18.5 kg) boy with a neurogenic bladder secondary to lumbar
      myelomeningocele. Urodynamics revealed a small capacity and poorly compliant
      bladder and he was incontinent between frequent catheterizations. A robotic
      augmentation cystoplasty was performed. RESULTS: At one-month postoperatively, a
      cystogram revealed no urine leak, and the suprapubic tube was removed. The
      patient resumed CIC every 3 h during the day and once overnight until
      postoperative urodynamic studies confirmed safe dynamics, after which the CIC
      interval was lengthened. CONCLUSION: Robotic bladder augmentation is safe and
      feasible in a select pediatric population. The entire procedure including
      preparation of the bowel segment can be completed intracorporeally, even in
      smaller children.

PMID- 27687534
TI  - Characterizing the intersection of Co-occurring risk factors for illicit drug
      abuse and dependence in a U.S. nationally representative sample.
AB  - Few studies have attempted to characterize how co-occurring risk factors for
      substance use disorders intersect. A recent study examined this question
      regarding cigarette smoking and demonstrated that co-occurring risk factors
      generally act independently. The present study examines whether that same pattern
      of independent intersection of risk factors extends to illicit drug
      abuse/dependence using a U.S. nationally representative sample (National Survey
      on Drug Use and Health, 2011-2013). Logistic regression and classification and
      regression tree (CART) modeling were used to examine risk of past-year drug
      abuse/dependence associated with a well-established set of risk factors for
      substance use (age, gender, race/ethnicity, education, poverty, smoking status,
      alcohol abuse/dependence, mental illness). Each of these risk factors was
      associated with significant increases in the odds of drug abuse/dependence in
      univariate logistic regressions. Each remained significant in a multivariate
      model examining all eight risk factors simultaneously. CART modeling of these 8
      risk factors identified subpopulation risk profiles wherein drug abuse/dependence
      prevalence varied from <1% to >80% corresponding to differing combinations of
      risk factors present. Alcohol abuse/dependence and cigarette smoking had the
      strongest associations with drug abuse/dependence risk. These results demonstrate
      that co-occurring risk factors for illicit drug/abuse dependence generally
      intersect in the same independent manner as risk factors for cigarette smoking,
      underscoring further fundamental commonalities across these different types of
      substance use disorders. These results also underscore the fundamental importance
      of differences in the presence of co-occurring risk factors when considering the
      often strikingly different prevalence rates of illicit drug abuse/dependence in
      U.S. population subgroups.

PMID- 27687536
TI  - A comprehensive scoring system to measure healthy community design in land use
      plans and regulations.
AB  - Comprehensive land use plans and their corresponding regulations play a role in
      determining the nature of the built environment and community design, which are
      factors that influence population health and health disparities. To determine the
      level in which a plan addresses healthy living and active design, there is a need
      for a systematic, reliable and valid method of analyzing and scoring health
      related content in plans and regulations. This paper describes the development
      and validation of a scoring tool designed to measure the strength and
      comprehensiveness of health-related content found in land use plans and the
      corresponding regulations. The measures are scored based on the presence of a
      specific item and the specificity and action-orientation of language. To
      establish reliability and validity, 42 land use plans and regulations from across
      the United States were scored January-April 2016. Results of the psychometric
      analysis indicate the scorecard is a reliable scoring tool for land use plans and
      regulations related to healthy living and active design. Intraclass correlation
      coefficients (ICC) scores showed strong inter-rater reliability for total
      strength and comprehensiveness. ICC scores for total implementation scores showed
      acceptable consistency among scorers. Cronbach's alpha values for all focus areas
      were acceptable. Strong content validity was measured through a committee vetting
      process. The development of this tool has far-reaching implications, bringing
      standardization of measurement to the field of land use plan assessment, and
      paving the way for systematic inclusion of health-related design principles,
      policies, and requirements in land use plans and their corresponding regulations.

PMID- 27687535
TI  - Impact of provider-patient communication on cancer screening adherence: A
      systematic review.
AB  - Cancer screening is critical for early detection and a lack of screening is
      associated with late-stage diagnosis and lower survival rates. The goal of this
      review was to analyze studies that focused on the role of provider-patient
      communication in screening behavior for cervical, breast, and colorectal cancer.
      A comprehensive search was conducted in four online databases between 1992 and
      2016. Studies were included when the provider being studied was a primary care
      provider and the communication was face-to-face. The search resulted in 3252
      records for review and 35 articles were included in the review. Studies were
      divided into three categories: studies comparing recommendation status to
      screening compliance; studies examining the relationship between communication
      quality and screening behavior; and intervention studies that used provider
      communication to improve screening behavior. There is overwhelming evidence that
      provider recommendation significantly improves screening rates. Studies examining
      quality of communication are heterogeneous in method, operationalization and
      results, but suggest giving information and shared decision making had a
      significant relationship with screening behavior. Intervention studies were
      similarly heterogeneous and showed positive results of communication
      interventions on screening behavior. Overall, results suggest that provider
      recommendation is necessary but not sufficient for optimal adherence to cancer
      screening guidelines. Quality studies suggest that provider-patient communication
      is more nuanced than just a simple recommendation. Discussions surrounding the
      recommendation may have an important bearing on a person's decision to get
      screened. Research needs to move beyond studies examining recommendations and
      adherence and focus more on the relationship between communication quality and
      screening adherence.

PMID- 27687537
TI  - Repletion of vitamin D associated with deterioration of sleep quality among
      postmenopausal women.
AB  - Reduced health-related quality of life (HRQOL), depressive symptoms and poor
      sleep quality are important health issues among postmenopausal women and may be
      associated with low vitamin D status. Overweight postmenopausal women, with serum
      25-hydroxyvitamin D [25(OH)D] 10-32ng/m, were recruited in Seattle, WA (2010
      2012) and randomly assigned to 12months of weight loss +2000IU oral vitamin
      D3/day or weight loss+daily placebo. The weight-loss program included a reduced
      calorie diet and 225min/week of moderate-to-vigorous aerobic activity. Eight
      subscales of HRQOL were assessed by the MOS 36-Item Short-Form Health Survey.
      Depressive symptoms were assessed using the Brief Symptom Inventory-18, and sleep
      quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Mean 12
      month changes in HRQOL, depressive symptoms and sleep quality were compared
      between groups (intent-to-treat) using generalized estimating equations. Compared
      to placebo, women receiving vitamin D did not experience any significant change
      in depressive symptoms (p=0.78), HRQOL subscales (all p>0.05), or overall sleep
      quality (p=0.21). However, a greater magnitude of change in serum 25(OH)D was
      associated with an increased need to take medications to sleep (ptrend=0.01) and
      overall worse sleep quality (ptrend<0.01). Women who became vitamin D replete
      (>=32ng/mL) also showed a deterioration in total PSQI sleep quality score
      compared to women who remained <32ng/mL despite supplementation, even after
      adjusting for relevant covariates (Non-Replete: -5.7% vs. Replete: +6.2%,
      p<0.01). Vitamin D supplementation of 2000IU/d may result in overall worse sleep
      quality for postmenopausal women with low circulating vitamin D undergoing weight
      loss.

PMID- 27687538
TI  - Effectiveness of a scaled up physical activity intervention in Brazil: A natural
      experiment.
AB  - Physical inactivity causes 5.3 million deaths annually worldwide. We evaluated
      the impact on population leisure-time physical activity (LTPA) of scaling up an
      intervention in Brazil, Academia das Cidades program (AC-P). AC-P is a health
      promotion program classified as physical activity classes in community settings
      which started in the state of Pernambuco state in 2008. We surveyed households
      from 80 cities of Pernambuco state in 2011, 2012 and 2013, using monitoring data
      to classify city-level exposure to AC-P. We targeted 2370 individuals in 2011;
      3824 individuals in 2012; and 3835 individuals in 2013. We measured participation
      in AC-P and whether respondents had seen an AC-P activity or heard about AC-P. We
      measured LTPA using the International Physical Activity Questionnaire. We
      estimated the odds of reaching recommended LTPA by levels of exposure to the
      three AC-P measures. For women, the odds of reaching recommended LTPA were 1.10
      for those living in cities with AC-P activity for less than three years, and 1.46
      for those living in cities with AC-P activity for more than three years compared
      to those living in cities that had not adopted AC-P. The odds of reaching
      recommended LTPA increased with AC-P participation and knowledge about AC-P. AC-P
      exposure is associated with increased population LTPA. Extending AC-P to all
      cities could potentially impact non-communicable diseases in Brazil.

PMID- 27687539
TI  - The MacTRAUMA TTL Assessment Tool: Developing a Novel Tool for Assessing
      Performance of Trauma Trainees: Initial Reliability Testing.
AB  - OBJECTIVES: To develop a novel assessment tool for trainees-led trauma
      resuscitation. Assess psychometric properties of the proposed tool. Evaluate
      feasibility and utility of the tool. INTRODUCTION: Trauma resuscitation is a
      structured and complex process involving unique sets of skills. There is
      currently no published structured formative evaluation tool for trauma trainees.
      Therefore, many trauma trainees rely upon limited, unstructured feedback on their
      performance. We developed a tool to assess trainee performance while leading a
      trauma resuscitation and to assist faculty in providing trainee feedback after
      the encounter. METHODS: This study was conducted in a level I trauma centre in
      Ontario, Canada. Principles of learning theories, literature review, and clinical
      expert opinions were used to design a tool to assess clinical competence required
      to lead the resuscitation. In total, 5 critical domains were identified. High
      fidelity simulation-based environment was used to test interrater reliability
      using intraclass correlation coefficients. To gauge feasibility, practicality,
      and utility of the tool, an online survey was sent to raters and trainees at the
      end of the study. RESULTS: We found "excellent" agreement for "initial critical
      assessment" domain (0.80) and "moderate to good" agreement for the "communication
      and leadership" (0.67) and "clinical performance" domains (0.53). "Poor"
      agreement was identified for the "decision-making" domain (0.33). The
      coefficients for individual items reached "good" agreement for 5 items, and
      "moderate" agreement for 8 items. Intraclass correlation coefficients for the
      remaining 7 items were "fair" or "poor." Most raters agreed that items in the
      medical training domain were not applicable. Feedback from raters and trainees
      confirmed the feasibility and acceptability of the tool for formative feedback,
      in addition to some suggestions to enhance the tool. CONCLUSION: MacTrauma TTL
      assessment tool is a novel tool for formative feedback for trainees' performance
      during trauma resuscitation. Initial psychometric property testing is promising.
      Further reliability and validity testing of the modified tool is needed. The tool
      has been shown to be feasible and acceptable by both trainees and faculty as a
      formative assessment tool.

PMID- 27687540
TI  - Analysis of Practice Settings for Craniofacial Surgery Fellowship Graduates in
      North America.
AB  - OBJECTIVE: In North America, the number of craniofacial surgery fellowship
      graduates is increasing, yet an analysis of practice settings upon graduation is
      lacking. We characterize the practice types of recent graduates of craniofacial
      fellowship programs in the United States and Canada. DESIGN: A 6-year cohort of
      craniofacial fellows in the United States and Canada (2010-2016) were obtained
      from craniofacial programs recognized by the American Society of Craniofacial
      Surgery. Practice setting was determined at 1 and 3 years of postgraduation, and
      predictors of practice setting were determined. RESULTS: A total of 175
      craniofacial surgeons were trained at 35 fellowship programs. At 1 year of
      postgraduation, 33.6% had an academic craniofacial position and 27.1% were in
      private practice (p = 0.361). A minority of graduates pursued additional
      fellowships (16.4%), nonacademic craniofacial positions (10.0%), academic
      noncraniofacial positions (5.7%), and international practices (7.1%). At 3 years
      of postgraduation, the percentage of graduates in academic craniofacial positions
      was unchanged (34.5% vs 33.6%, p = 0.790). The strongest predictors of future
      academic craniofacial practice were completing plastic surgery residency at a
      program with a craniofacial fellowship program (odds ratio = 6.78, p < 0.001) and
      completing an academic craniofacial fellowship program (odds ratio = 4.48, p =
      0.020). CONCLUSIONS: A minority of craniofacial fellowship graduates practice
      academic craniofacial surgery. A strong academic craniofacial surgery background
      during residency and fellowship is associated with a future career in academic
      craniofacial surgery. These data may assist trainees choose training programs
      that align with career goals and educators select future academic surgeons.

PMID- 27687541
TI  - Cholesterol-rich membrane microdomains modulate Wnt/beta-catenin morphogen
      gradient during Xenopus development.
AB  - Wnt/beta-catenin has been described as crucial for dorsal-ventral and antero
      posterior patterning, playing multiple roles at different stages of development.
      Cholesterol-rich membrane microdomains (CRMMs), cholesterol- and sphingolipid
      enriched domains of the plasma membrane, are known as platforms for signaling
      pathways. Although we have demonstrated the importance of the CRMMs for head
      development, how they participate in prechordal plate formation and embryo axis
      patterning remains an open question. Moreover, the participation of the CRMMs in
      the Wnt/beta-catenin signaling pathway activity in vivo is unclear, particularly
      during embryonic development. In this study, we demonstrated that CRMMs
      disruption by methyl-beta-cyclodextrin (MbetaCD) potentiates the activation of
      the Wnt/beta-catenin signaling pathway in vitro and in vivo during embryonic
      development, causing head defects by expanding the Wnt expression domain.
      Furthermore, we also found that the action of CRMMs depends on the
      microenvironmental context because it also works in conjunction with dkk1, when
      dkk1 is overexpressed. Thus, we propose CRMMs as a further mechanism of
      prechordal plate protection against the Wnt signals secreted by posterolateral
      cells, complementing the action of secreted antagonists.

PMID- 27687542
TI  - New Gleason grading system: Statement from the editors of 6 journals.

PMID- 27687543
TI  - Evaluation of beta-blockers and survival among hypertensive patients with renal
      cell carcinoma.
AB  - OBJECTIVES: Beta-blocker use is associated with improved survival for multiple
      nonurologic malignancies. Our objective was to evaluate the association between
      beta-blocker use and survival among surgically managed hypertensive patients with
      clear-cell renal cell carcinoma (ccRCC). METHODS: Hypertensive patients with
      ccRCC treated with either radical or partial nephrectomy between 2000 and 2010
      were identified from our Nephrectomy Registry. Beta-blocker use within 90 days
      before surgery was identified. The associations between beta-blocker use and risk
      of disease progression, death from renal cell carcinoma (RCC), and all-cause
      mortality were assessed using Cox proportional hazards regression models.
      RESULTS: In total, 913 hypertensive patients were identified who underwent either
      partial or radical nephrectomy for ccRCC. Of these, 104 (11%) had documented beta
      blocker use within 90 days before surgery. At last follow-up (median 8.2y among
      survivors), 258 patients showed progression (median 1.6y following surgery), and
      369 patients had died (median 4.1y following surgery), including 138 who died of
      RCC. After adjusting for PROG (progression-free survival) and SSIGN (cancer
      specific survival) scores, beta-blocker use was not significantly associated with
      the risk of disease progression (hazard ratio [HR] = 0.94; 95% CI: 0.61-1.47; P =
      0.80) or the risk of death from RCC (HR = 0.74; 95% CI: 0.38-1.41; P = 0.35).
      Similarly, on multivariable analysis adjusting for clinicopathologic features,
      there was not a significant association between beta-blocker use and the risk of
      all-cause mortality (HR = 0.83; 95% CI: 0.59-1.16; P = 0.27). CONCLUSIONS: Beta
      blocker use for hypertension within 90 days before surgery was not associated
      with the risk of progression, death from RCC, or death from any cause.

PMID- 27687544
TI  - Effect of delayed resection after initial surveillance and tumor growth rate on
      final surgical pathology in patients with small renal masses (SRMs).
AB  - OBJECTIVE: To understand potential harms associated with delaying resection of
      small renal masses (SRMs) in patients ultimately treated, and whether these
      patients have factors associated with adverse pathology. METHODS: Patients with
      SRMs (<=4cm) who underwent surgical resection at our institution (2009-2015) were
      classified as undergoing early resection or initial surveillance with delayed
      resection (defined by a time from presentation to intervention of at least 6mo).
      Demographic and clinical variables were compared among groups. Using
      multivariable logistic regression, we examined the association between delayed
      resection and adverse pathology (Fuhrman grade 3-4, papillary type 2, sarcomatoid
      histology, angiomyolipoma with epithelioid features, or stage>=pT3). For patients
      who underwent delayed intervention, we used similar methods to examine the
      association between SRM growth rate and adverse pathology. RESULTS: Overall, 401
      (81%) and 94 (19%) patients underwent early and delayed resection, respectively.
      Median time to resection was 84 days (interquartile range: 59-121) and 386 days
      (interquartile range: 272-702) (P<0.001). Patients undergoing delayed resection
      were older (62 vs. 58y, P = 0.01) and had smaller masses (2.3 vs. 2.7cm, P<0.001)
      at initial presentation. Utilization of partial vs. radical nephrectomy was
      similar regardless of resection timing (P = 0.5). Delayed resection was not
      associated with adverse pathology (P = 0.8); however, male sex was independently
      associated with adverse pathology (odds ratio: 1.7, 95% CI: 1.1-2.4, P = 0.009).
      In patients on surveillance, increasing annual SRM growth rate was associated
      with adverse pathology (odds ratio: 1.2, 95% CI: 1.03-1.3mm/y, P = 0.02).
      CONCLUSIONS: Delayed resection was not associated with adverse pathology.
      Patients on surveillance with increased SRM growth rates had a modest but
      significant increase in the risk of adverse pathology.

PMID- 27687545
TI  - Mechanism of paclitaxel resistance in a human prostate cancer cell line, PC3-PR,
      and its sensitization by cabazitaxel.
AB  - Paclitaxel (PTX) is a microtubule-targeting drug widely used for the treatment of
      a variety of cancers. However, drug resistance can emerge after a series of
      treatments, and this can seriously affect the patient's prognosis. Here, we
      analyzed the mechanism of PTX resistance using a human prostate cancer cell line,
      PC3, and its PTX-resistant subline, PC3-PR. Compared with PC3, PC3-PR exhibited
      some unique phenotypes that might be associated with PTX resistance, including
      decreased expression of acetylated alpha-tubulin and the cell cycle regulator
      p21, and increased expression of betaIII tubulin, histone deacetylase 6 (HDAC6),
      and the anti-apoptotic protein Bcl2. The drug exporters MDR1 and MRP1 were not
      involved in PTX resistance. Although cabazitaxel (CTX), a novel taxoid, has been
      reported to overcome PTX resistance, its mechanism of action is unknown. We found
      that treatment of PC3-PR cells with CTX induced expression of acetylated alpha
      tubulin and p21, but not the related regulators p27, p15, and p16 or the Bcl2
      family proteins. The pan-HDAC inhibitors trichostatin A and suberanilohydroxamic
      acid and the HDAC6-specific inhibitor tubacin inhibited PC3-PR proliferation and
      increased expression of p21 and acetylated alpha-tubulin in a manner similar to
      CTX. Our data shed light on the cellular response to PTX and CTX.

PMID- 27687546
TI  - Wnt4 antagonises Wnt3a mediated increases in growth and glucose stimulated
      insulin secretion in the pancreatic beta-cell line, INS-1.
AB  - The Wnt signalling pathway in beta-cells has been linked to the development of
      type 2 diabetes. Investigating the impact of a non-canonical Wnt ligand, Wnt4, on
      beta-cell function we found that in INS-1 cells, Wnt4 was able to completely
      block Wnt3a stimulated cell growth and insulin secretion. However, despite high
      levels of Wnt4 protein being detected in INS-1 cells, reducing the expression of
      Wnt4 had no impact on cell growth or Wnt3a signalling. As such, the role of the
      endogenously expressed Wnt4 in beta-cells is unclear, but the data showing that
      Wnt4 can act as a negative regulator of canonical Wnt signalling in beta-cells
      suggests that this pathway could be a potential target for modulating beta-cell
      function.

PMID- 27687547
TI  - Chemotherapy impedes in vitro microcirculation and promotes migration of leukemic
      cells with impact on metastasis.
AB  - Although most cancer drugs target the proliferation of cancer cells, it is
      metastasis, the complex process by which cancer cells spread from the primary
      tumor to other tissues and organs of the body where they form new tumors, that
      leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti
      metastasis therapy. Surprisingly, emerging evidence suggests that certain anti
      cancer drugs such as paclitaxel and doxorubicin can actually promote metastasis,
      but the mechanism(s) behind their pro-metastatic effects are still unclear. Here,
      we use a microfluidic microcirculation mimetic (MMM) platform which mimics the
      capillary constrictions of the pulmonary and peripheral microcirculation, to
      determine if in-vivo-like mechanical stimuli can evoke different responses from
      cells subjected to various cancer drugs. In particular, we show that leukemic
      cancer cells treated with doxorubicin and daunorubicin, commonly used anti-cancer
      drugs, have over 100% longer transit times through the device, compared to
      untreated leukemic cells. Such delays in the microcirculation are known to
      promote extravasation of cells, a key step in the metastatic cascade.
      Furthermore, we report a significant (p < 0.01) increase in the chemotactic
      migration of the doxorubicin treated leukemic cells. Both enhanced retention in
      the microcirculation and enhanced migration following chemotherapy, are pro
      metastatic effects which can serve as new targets for anti-metastatic drugs.

PMID- 27687548
TI  - NSAIDs diclofenac, indomethacin, and meloxicam highly upregulate expression of
      ICAM-1 and COX-2 induced by X-irradiation in human endothelial cells.
AB  - BACKGROUND: It is well known that radiation exposure to the heart and the use of
      non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of myocardial
      infarction (MI). Some NSAIDs are also known to act synergistically with ionizing
      radiation and have radio-sensitizing effects in radiotherapy. These evidences
      suggest that NSAIDs may affect the risk of MI after radiation exposure to the
      heart. In the present study, we investigated effects of NSAIDs on radiation
      induced expression of cell adhesion molecules and COX-2, which are associated
      with inflammation and an increased risk of MI, in human endothelial cells.
      METHODS: Effects of NSAIDs on radiation-induced expression of ICAM-1, VCAM-1, E
      selectin, and COX-2 were investigated in human umbilical vein endothelial cells
      (HUVECs). As NSAIDs, diclofenac, etodolac, indomethacin, ketoprofen, meloxicam,
      and rofecoxib were used. RESULTS: Irradiation with 10 Gy increased expression of
      ICAM-1 and COX-2, but it did not affect expression of VCAM-1 or E-selectin. All
      the NSAIDs upregulated radiation-induced expression of ICAM-1 and COX-2. The
      extent of upregulation varied depending on the types of NSAIDs. Indomethacin,
      diclofenac, and meloxicam highly upregulated radiation-induced expression of ICAM
      1 and COX-2. The extent of upregulation was not related to the degree of COX-2
      selectivity. An NF-kappaB inhibitor BAY 11-7082 suppressed radiation-induced
      expression of ICAM-1, but it did not suppress upregulated expression of ICAM-1 or
      COX-2 by combination treatment with X-irradiation and meloxicam, suggesting the
      existence of NF-kappaB-independent pathways for ICAM-1 and COX-2 induction.
      CONCLUSION: Indomethacin, diclofenac, and meloxicam highly upregulated radiation
      induced expression of ICAM-1 and COX-2 in HUVECs, which suggests that use of
      these NSAIDs may increase the effects of ionizing radiation and affect the risk
      of MI after radiation exposure to the heart.

PMID- 27687549
TI  - Mitochondrial DNA mutation m.5512A > G in the acceptor-stem of mitochondrial
      tRNATrp causing maternally inherited essential hypertension.
AB  - Essential hypertension (EH) is a common complex disorder with high heritability.
      Maternal inherited pattern was observed in some families with EH, which was known
      as maternally inherited essential hypertension (MIEH). Mitochondrial DNA (mtDNA)
      mutations were identified to account for some MIEH in previous studies. In the
      present study, we characterized clinical manifestations and the complete
      mitochondrial genome of a Chinese family with MIEH. Through analyzing the whole
      mtDNA genome of the proband, we identified a mutation m.5512A > G in the MT-TW
      gene that changed a highly conserved nucleotide and could potentially affect the
      function of tRNATrp. Furthermore, significantly exercise intolerance, left
      ventricular remodeling and increased arterial stiffness were observed in carriers
      with mutation m.5512A > G, which further supported the potentially pathogenic
      effect of m.5512A > G in MIEH.

PMID- 27687550
TI  - A-to-I RNA editing of the IGFBP7 transcript increases during aging in porcine
      brain tissues.
AB  - The IGFBP7 gene encodes insulin-like growth factor protein 7. IGFPB7 is involved
      in diverse biological functions including cell growth regulation, senescence and
      apoptosis, and also acts as a tumor suppressor in multiple cancers. The IGFBP7
      mRNA is subject to A-to-I RNA editing mediated by adenosine deaminases acting on
      RNA 1 and 2 (ADAR1 and ADAR2). In the current study we have examined molecular
      characteristics of the porcine IGFBP7 gene, and determined the mRNA editing in
      different tissues. The A-to-I RNA editing of human IGFBP7 in positions Arg78 and
      Lys95 was shown to be conserved in the porcine homologue. In addition, a novel
      editing site was discovered in position Lys97 in the porcine IGFBP7 transcript. A
      differential editing was demonstrated at the three positions in the IGFBP7
      transcript with very high degrees of editing in frontal cortex, cerebellum and
      lung. Interestingly, the degree of editing increased during aging in porcine
      frontal cortex and cerebellum. The IGFBP7 gene was mapped to pig chromosome 8.
      The porcine IGFBP7 gene was found to be ubiquitously expressed in examined organs
      and tissues. The methylation status of the IGFBP gene was examined in brain and
      liver by bisulfate sequencing and a high degree of methylation was found in the
      two tissues, 52% and 54%, respectively.

PMID- 27687551
TI  - The IAB Congress 2016: Is there justice in the bioethics world?
AB  - This comment contains the reflections of a first-time participant in the 13th
      International Association of Bioethics Congress (IAB 2016), held from June 14 to
      17, 2016, in Edinburgh. At the outset, I would like to make a couple of
      clarifications. First, the opinions expressed here are my personal reflections
      and second, I am a physician and public health practitioner by profession and my
      interest is bioethics. I reflect on the justice implications of the IAB 2016 from
      the perspective of the challenge of maintaining inclusivity in a
      multidisciplinary bioethics world.

PMID- 27687552
TI  - A computer-human interaction model to improve the diagnostic accuracy and
      clinical decision-making during 12-lead electrocardiogram interpretation.
AB  - INTRODUCTION: The 12-lead Electrocardiogram (ECG) presents a plethora of
      information and demands extensive knowledge and a high cognitive workload to
      interpret. Whilst the ECG is an important clinical tool, it is frequently
      incorrectly interpreted. Even expert clinicians are known to impulsively provide
      a diagnosis based on their first impression and often miss co-abnormalities.
      Given it is widely reported that there is a lack of competency in ECG
      interpretation, it is imperative to optimise the interpretation process.
      Predominantly the ECG interpretation process remains a paper based approach and
      whilst computer algorithms are used to assist interpreters by providing printed
      computerised diagnoses, there are a lack of interactive human-computer interfaces
      to guide and assist the interpreter. METHODS: An interactive computing system was
      developed to guide the decision making process of a clinician when interpreting
      the ECG. The system decomposes the interpretation process into a series of
      interactive sub-tasks and encourages the clinician to systematically interpret
      the ECG. We have named this model 'Interactive Progressive based Interpretation'
      (IPI) as the user cannot 'progress' unless they complete each sub-task. Using
      this model, the ECG is segmented into five parts and presented over five user
      interfaces (1: Rhythm interpretation, 2: Interpretation of the P-wave morphology,
      3: Limb lead interpretation, 4: QRS morphology interpretation with chest lead and
      rhythm strip presentation and 5: Final review of 12-lead ECG). The IPI model was
      implemented using emerging web technologies (i.e. HTML5, CSS3, AJAX, PHP and
      MySQL). It was hypothesised that this system would reduce the number of
      interpretation errors and increase diagnostic accuracy in ECG interpreters. To
      test this, we compared the diagnostic accuracy of clinicians when they used the
      standard approach (control cohort) with clinicians who interpreted the same ECGs
      using the IPI approach (IPI cohort). RESULTS: For the control cohort, the (mean;
      standard deviation; confidence interval) of the ECG interpretation accuracy was
      (45.45%; SD=18.1%; CI=42.07, 48.83). The mean ECG interpretation accuracy rate
      for the IPI cohort was 58.85% (SD=42.4%; CI=49.12, 68.58), which indicates a
      positive mean difference of 13.4%. (CI=4.45, 22.35) An N-1 Chi-square test of
      independence indicated a 92% chance that the IPI cohort will have a higher
      accuracy rate. Interpreter self-rated confidence also increased between cohorts
      from a mean of 4.9/10 in the control cohort to 6.8/10 in the IPI cohort (p=0.06).
      Whilst the IPI cohort had greater diagnostic accuracy, the duration of ECG
      interpretation was six times longer when compared to the control cohort.
      CONCLUSIONS: We have developed a system that segments and presents the ECG across
      five graphical user interfaces. Results indicate that this approach improves
      diagnostic accuracy but with the expense of time, which is a valuable resource in
      medical practice.

PMID- 27687553
TI  - Efficacy and Safety of Bevacizumab Combined With Fluoropyrimidine Monotherapy for
      Unfit or Older Patients With Metastatic Colorectal Cancer: A Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: Whether bevacizumab represents a feasible option for the first-line
      treatment of unfit and elderly patients with metastatic colorectal cancer (mCRC)
      remains controversial. The present systematic review and meta-analysis evaluated
      the efficacy and safety data of bevacizumab combined with first-line
      fluoropyrimidine monochemotherapy for these complex patients. PATIENTS AND
      METHODS: A systematic search of the published data was conducted through May 31,
      2016. The random-effects model was used to combine the effect estimates and the
      I2 index to quantify the between-study heterogeneity unexplained by sampling
      error. RESULTS: We included 3 randomized controlled trials, 4 single-arm phase II
      trials, and 1 prospective cohort study in the present meta-analysis (n = 782).
      The monochemotherapy administered was capecitabine in 531 patients (67.9%) and 5
      fluorouracil in 251 (32.1%); 500 (63.9%) also received bevacizumab. The median
      age was 75 years, 441 patients (56.4%) were men, and the Eastern Cooperative
      Oncology Group performance status was 0 to 1 in 684 patients (87.7%). The
      combination with bevacizumab produced advantages in terms of both progression
      free survival (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64; P <
      .00001; I2 = 0%) and overall survival (HR, 0.79; 95% CI, 0.64-0.98; P = .03; I2 =
      0%). The pooled effect estimates of the randomized controlled trials have been
      previously reported. As expected, all-grade hypertension (27% vs. 4.9%), bleeding
      (24% vs. 6.4%), thromboembolic events (10% vs. 5%), and proteinuria (25.6% vs.
      8.2%) were more frequent in the bevacizumab combination group. CONCLUSION: Adding
      bevacizumab to first-line fluoropyrimidine monochemotherapy significantly
      improved progression-free and overall survival in unfit and elderly patients with
      mCRC, with a manageable safety profile and no unexpected toxicities.

PMID- 27687554
TI  - Reply to the letter: Urine based molecular diagnosis of Zika virus by Viroj
      Wiwanitkit.

PMID- 27687557
TI  - Cacogenic Cartographies: Space and Place in the Eugenic Family Study.
AB  - Though only one component product of the larger eugenics movement, the eugenic
      family study proved to be, by far, its most potent ideological tool. The Kallikak
      Family, for instance, went through eight editions between 1913 and 1931. This
      essay argues that the current scholarship has missed important ways that the
      architects of the eugenic family studies theorized and described the subjects of
      their investigation. Using one sparsely interrogated work (sociologist Frank
      Wilson Blackmar's "The Smoky Pilgrims") and one previously unknown eugenic family
      study (biologist Frank Gary Brooks' untitled analysis of the flood-zone
      Oklahomans) from the Southern Plains, this essay aims to introduce "environment"
      as a schema that allows for how the subjects of the eugenic family study were
      conceptualized with respect to their surroundings. Geospatially and
      environmentally relevant constructions of scientific knowledge were central to
      the project of eugenics during its formative years, but remain largely and
      conspicuously absent from the critical literature which engages this project to
      separate the fit from the unfit in American society. The dysgenic constituted a
      unique human geography, giving us significant insight into how concatenations of
      jurisprudence as well as cultural and social worth were tied to the land.

PMID- 27687555
TI  - Enhanced Th1 and Th17 responses in peripheral blood in active non-segmental
      vitiligo.
AB  - Accumulating studies have indicated that vitiligo, especially non-segmental
      vitiligo (NSV), is one kind of autoimmune diseases and CD4+ T cells play
      important roles in the pathogenesis. However, there have been very limited data
      on the detailed changes of each of the CD4+ T cell subsets in periphery in active
      NSV. To clarify this issue, we collected the peripheral blood mononuclear cells
      (PBMCs) from 30 patients with active NSV and 30 age- and sex-matched healthy
      controls. The percentages of circulating Th1, Th2, Th17 and Tregs were evaluated
      using flow cytometry and the expressions of their specific transcription factors
      T-bet, GATA3, RORgammat and FOXP3 at mRNA level and protein levels were qualified
      by qPCR and flow cytometry, respectively. Meanwhile, the expression levels of IFN
      gamma, IL-4, TGF-beta, and IL-17A in serum were measured. We found that in
      patients with NSV, the percentages and absolute numbers of circulating Th1 and
      Th17 were both significantly higher than those of healthy controls, while the
      percentages of Th2 and Tregs and absolute numbers showed no significant
      difference compared to healthy controls. Moreover, the ratios of Th1/Tregs and
      Th17/Tregs in circulation were both statistically elevated in active NSV. Similar
      results were got in qualification of their corresponding transcription factors at
      mRNA level and protein levels. Compared with healthy controls, the expression
      level of IL-17A was significantly increased in serum of patients with NSV, while
      the productions of IFN-gamma, IL-4, TGF-beta had no significant change. These
      data suggested that in circulating CD4+ T cell subsets, Th1 and Th17 played the
      major role in cellular immunity in the progression of vitiligo. The immune lever
      in circulation was inclined to effector CD4+ T cells not suppressor CD4+ T cells
      that may result in the loss of self-tolerance to melanocytes.

PMID- 27687556
TI  - Walking through an aperture with visual information obtained at a distance.
AB  - The present study addressed whether visual information about the width of an
      aperture, obtained at a distance, would be sufficient to guide walking through
      the aperture without collision. For this purpose, we asked twelve young
      participants to walk while holding a 66-cm horizontal bar (bar length needs to be
      considered in order to perceive space necessary for crossing) and pass through an
      aperture without vision from 3 m in front of the aperture. Participants performed
      the tasks under each of four visual conditions, which differed in how vision was
      available: observation for 1.5 s while standing (static vision), observation
      during two forward steps and stopping (dynamic vision), observation during two
      forward steps and not stopping (dynamic vision with nonstop walking), and full
      vision. The results showed that, for narrow apertures (the widths were 0.8 and
      1.0 times the bar length), the rate of collision without vision was about 40-50
      %. This was mainly due to the maladaptive planning of body rotation. For the
      aperture 1.0 times the bar length, the percentage of trials with no body rotation
      was high, suggesting that at least some participants underestimated the space
      necessary for crossing. The location at which maximum body rotation occurred
      became farther from the obstacle, which may have been related to decreased
      movement speed. The availability of dynamic visual sampling during two forward
      steps did not contribute to improving collision avoidance. These results suggest
      that, while fundamental locomotor patterns are maintained even without online
      vision, both the underestimation of space required for crossing and the lack of
      fine-tuning of behavior prior to crossing increased collision rates.

PMID- 27687558
TI  - The prefrontal oxygenation and ventilatory responses at start of one-legged
      cycling exercise have relation to central command.
AB  - When performing exercise arbitrarily, activation of central command should start
      before the onset of exercise, but when exercise is forced to start with cue,
      activation of central command should be delayed. We examined whether the in
      advance activation of central command influenced the ventilatory response and
      reflected in the prefrontal oxygenation, by comparing the responses during
      exercise with arbitrary and cued start. The breath-by-breath respiratory
      variables and the prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) were
      measured during one-legged cycling. Minute ventilation (Ve) at the onset of
      arbitrary one-legged cycling was augmented to a greater extent than cued cycling,
      while end-tidal carbon dioxide tension (ETco2) decreased irrespective of
      arbitrary or cued start. Symmetric increase in the bilateral prefrontal Oxy-Hb
      occurred before and at the onset of arbitrary one-legged cycling, whereas such an
      increase was absent with cued start. The time course and magnitude of the
      increased prefrontal oxygenation were not influenced by the extent of subjective
      rating of perceived exertion and were the same as those of the prefrontal
      oxygenation during two-legged cycling previously reported. Mental imagery or
      passive performance of the one-legged cycling increased Ve and decreased ETco2
      Neither intervention, however, augmented the prefrontal Oxy-Hb. The changes in
      ETco2 could not explain the prefrontal oxygenation response during voluntary or
      passive one-legged cycling. Taken together, it is likely that the in-advance
      activation of central command influenced the ventilatory response by enhancing
      minute ventilation at the onset of one-legged cycling exercise and reflected in
      the preexercise increase in the prefrontal oxygenation.

PMID- 27687559
TI  - Interstitial glucose concentrations and hypoglycemia during 2 days of caloric
      deficit and sustained exercise: a double-blind, placebo-controlled trial.
AB  - Military personnel and some athlete populations endure short-term energy deficits
      from reduced energy intake and/or increased energy expenditure (EE) that may
      degrade physical and cognitive performance due to severe hypoglycemia (<3.1
      mmol/l). The extent to which energy deficits alter normoglycemia (3.9-7.8 mmol/l)
      in healthy individuals is not known, since prior studies measured glucose
      infrequently, not continuously. The purpose of this study was to characterize the
      glycemic response to acute, severe energy deficit compared with fully fed control
      condition, using continuous glucose monitoring (CGM). For 2 days during a double
      blind, placebo-controlled, crossover study, 23 volunteers (17 men/6 women; age:
      21.3 +/- 3.0 yr; body mass index: 25 +/- 3 kg/m) increased habitual daily EE
      [2,300 +/- 450 kcal/day [means +/- SD)] by 1,647 +/- 345 kcal/day through
      prescribed exercise (~3 h/day; 40-65% peak O2 consumption), and consumed diets
      designed to maintain energy balance (FED) or induce 93% energy deficit (DEF).
      Interstitial glucose concentrations were measured continuously by CGM (Medtronic
      Minimed). Interstitial glucose concentrations were 1.0 +/- 0.9 mmol/l lower
      during DEF vs. FED (P < 0.0001). The percentage of time spent in mild (3.1-3.8
      mmol/l) hypoglycemia was higher during DEF compared with FED [mean difference =
      20.5%; 95% confidence interval (CI): 13.1%, 27.9%; P = 0.04], while time spent in
      severe (<3.1 mmol/l) hypoglycemia was not different between interventions (mean
      difference = 4.6%; 95% CI: -0.6%, 9.8%; P = 0.10). Three of 23 participants
      spontaneously reported symptoms (e.g., nausea) potentially related to
      hypoglycemia during DEF, and an additional participant reported symptoms during
      both interventions. These findings suggest that severe hypoglycemia rarely occurs
      in healthy individuals enduring severe, short-term energy deficit secondary to
      heavy exercise and inadequate energy intake.

PMID- 27687560
TI  - Effects of repetitive transcranial magnetic stimulation of upper airway muscles
      during sleep in obstructive sleep apnea patients.
AB  - We tested the hypothesis that stimulating the genioglossus by repetitive
      transcranial magnetic stimulation (rTMS) during the ascendant portion of the
      inspiratory flow of airflow-limited breaths would sustain the recruitment of
      upper airway dilator muscles over time and improve airway dynamics without
      arousing obstructive sleep apnea (OSA) patients. In a cross-sectional design,
      nine OSA patients underwent a rTMS trial during stable non-rapid eye movement
      (NREM) sleep. Submental muscle motor threshold (SUB) and motor-evoked potential
      were evaluated during wakefulness and sleep. During NREM sleep, maximal
      inspiratory flow, inspiratory volume, inspiratory time, shifts of
      electroencephalogram frequency, and pulse rate variability were assessed under
      three different stimulation paradigms completed at 1.2 sleep SUB stimulation
      output: 1) 5Hz-08 (stimulation frequency: 5 Hz; duration of train stimulation:
      0.8 s); 2) 25Hz-02 (stimulation frequency: 25 Hz; duration of train stimulation:
      0.2 s); and 3) 25Hz-04 (stimulation frequency: 25 Hz; duration of train
      stimulation: 0.4 s). SUB increased during NREM sleep (wakefulness: 23.8 +/- 6.1%;
      NREM: 26.8 +/- 5.2%; = 0.001). Two distinct airflow patterns were observed in
      response to rTMS: with and without initial airflow drops, without other airflow
      variables change regardless the stimulation paradigm applied. Finally, rTMS
      induced cortical and/or autonomic arousal were observed in 36, 26, and 35% of all
      delivered rTMS trains during 5Hz-08, 25Hz-02, and 25Hz-04 stimulation paradigms,
      respectively. In conclusion, rTMS does not provide any airflow improvement of
      flow-limited breaths as seen with nonrepetitive TMS of upper airway dilator
      muscles. However, rTMS trains were free of arousals in the majority of cases.

PMID- 27687561
TI  - Estimating oxygen uptake and energy expenditure during treadmill walking by
      neural network analysis of easy-to-obtain inputs.
AB  - The study of oxygen uptake (Vo2) dynamics during walking exercise transitions
      adds valuable information regarding fitness. However, direct Vo2 measurements are
      not practical for general population under realistic settings. Devices to measure
      Vo2 are associated with elevated cost, uncomfortable use of a mask, need of
      trained technicians, and impossibility of long-term data collection. The
      objective of this study was to predict the Vo2 dynamics from heart rate and
      inputs from the treadmill ergometer by a novel artificial neural network
      approach. To accomplish this, 10 healthy young participants performed one
      incremental and three moderate constant work rate treadmill walking exercises.
      The speed and grade used for the moderate-intensity protocol was related to 80%
      of the Vo2 response at the gas exchange threshold estimated during the
      incremental exercise. The measured Vo2 was used to train an artificial neural
      network to create an algorithm able to predict the Vo2 based on easy-to-obtain
      inputs. The dynamics of the Vo2 response during exercise transition were
      evaluated by exponential modeling. Within each participant, the predicted Vo2 was
      strongly correlated to the measured Vo2 ( = 0.97 +/- 0.0) and presented a low
      bias (~0.2%), enabling the characterization of the Vo2 dynamics during treadmill
      walking exercise. The proposed algorithm could be incorporated into smart devices
      and fitness equipment, making them suitable for tracking changes in aerobic
      fitness and physical health beyond the infrequent monitoring of patients during
      clinical interventions and rehabilitation programs.

PMID- 27687562
TI  - State-dependent and -independent effects of dialyzing excitatory neuromodulator
      receptor antagonists into the ventral respiratory column.
AB  - Unilateral dialysis of the broad-spectrum muscarinic receptor antagonist atropine
      (50 mM) into the ventral respiratory column [(VRC) including the pre-Botzinger
      complex region] of awake goats increased pulmonary ventilation (Vi) and breathing
      frequency (f), conceivably due to local compensatory increases in serotonin (5
      HT) and substance P (SP) measured in effluent mock cerebral spinal fluid (mCSF).
      In contrast, unilateral dialysis of a triple cocktail of antagonists to
      muscarinic (atropine; 5 mM), neurokinin-1, and 5-HT receptors does not alter Vi
      or f, but increases local SP. Herein, we tested hypotheses that 1) local
      compensatory 5-HT and SP responses to 50 mM atropine dialyzed into the VRC of
      goats will not differ between anesthetized and awake states; and 2) bilateral
      dialysis of the triple cocktail of antagonists into the VRC of awake goats will
      not alter Vi or f, but will increase local excitatory neuromodulators. Through
      microtubules implanted into the VRC of goats, probes were inserted to dialyze
      mCSF alone (time control), 50 mM atropine, or the triple cocktail of antagonists.
      We found 1) equivalent increases in local 5-HT and SP with 50 mM atropine
      dialysis during wakefulness compared with isoflurane anesthesia, but Vi and f
      only increased while awake; and 2) dialyses of the triple cocktail of antagonists
      increased Vi, f, 5-HT, and SP (<0.05) during both day and night studies. We
      conclude that the mechanisms governing local neuromodulator levels are state
      independent, and that bilateral excitatory receptor blockade elicits an increase
      in breathing, presumably due to a local, (over)compensatory neuromodulator
      response.NEW & NOTEWORTHY The two major findings are as follows: 1) during
      unilateral dialysis of 50 mM atropine into the ventral respiratory column to
      block excitatory muscarinic receptor activity, a compensatory increase in other
      neuromodulators was state independent, but the ventilatory response appears to be
      state dependent; and 2) the hypothesis that absence of decreased Vi and f during
      unilateral dialysis of excitatory receptor antagonists was due to compensation by
      the contralateral VRC was not supported by findings herein.

PMID- 27687564
TI  - Anemia contributes to cardiovascular disease through reductions in nitric oxide.

PMID- 27687563
TI  - Validity and reliability of measuring resting muscle sympathetic nerve activity
      using short sampling durations in healthy humans.
AB  - Resting muscle sympathetic nerve activity (MSNA) demonstrates high
      intraindividual reproducibility when sampled over 5-30 min epochs, although
      shorter sampling durations are commonly used before and during a stress to
      quantify sympathetic responsiveness. The purpose of the present study was to
      examine the intratest validity and reliability of MSNA sampled over 2 and 1 min
      and 30 and 15 s epoch durations. We retrospectively analyzed 68 resting fibular
      nerve microneurographic recordings obtained from 53 young, healthy participants
      (37 men; 23 +/- 6 yr of age). From a stable 7-min resting baseline, MSNA (burst
      frequency and incidence, normalized mean burst amplitude, total burst area) was
      compared among each epoch duration and a standard 5-min control. Bland-Altman
      plots were used to determine agreement and bias. Three sequential MSNA
      measurements were collected using each sampling duration to calculate absolute
      and relative reliability (coefficients of variation and intraclass correlation
      coefficients). MSNA values were similar among each sampling duration and the 5
      min control (all P > 0.05), highly correlated (r = 0.69-0.93; all P < 0.001), and
      demonstrated no evidence of fixed bias (all P > 0.05). A consistent proportional
      bias (P < 0.05) was present for MSNA burst frequency (all sampling durations) and
      incidence (1 min and 30 and 15 s), such that participants with low and high
      average MSNA underestimated and overestimated the true value, respectively.
      Reliability decreased progressively using the 30- and 15-s sampling durations. In
      conclusion, short 2 and 1 min and 30 s sampling durations can provide valid and
      reliable measures of MSNA, although increased sample size may be required for
      epochs <=30 s, due to poorer reliability.

PMID- 27687565
TI  - A Thousand Fly Genomes: An Expanded Drosophila Genome Nexus.
AB  - The Drosophila Genome Nexus is a population genomic resource that provides D.
      melanogaster genomes from multiple sources. To facilitate comparisons across data
      sets, genomes are aligned using a common reference alignment pipeline which
      involves two rounds of mapping. Regions of residual heterozygosity, identity-by
      descent, and recent population admixture are annotated to enable data filtering
      based on the user's needs. Here, we present a significant expansion of the
      Drosophila Genome Nexus, which brings the current data object to a total of 1,121
      wild-derived genomes. New additions include 305 previously unpublished genomes
      from inbred lines representing six population samples in Egypt, Ethiopia, France,
      and South Africa, along with another 193 genomes added from recently-published
      data sets. We also provide an aligned D. simulans genome to facilitate divergence
      comparisons. This improved resource will broaden the range of population genomic
      questions that can addressed from multi-population allele frequencies and
      haplotypes in this model species. The larger set of genomes will also enhance the
      discovery of functionally relevant natural variation that exists within and
      between populations.

PMID- 27687566
TI  - Assessing the biological activities of xanthone derivatives from Swertia
      macrosperma C.B. Clark.
AB  - The anti-microbial and anti-oxidant effects of xanthones extract from Swertia
      macrosperma C.B. Clark were investigated using extracts from whole plant and
      partitioned by petroleum ether, ethyl acetate and n-butanol, respectively. Anti
      microbial and anti-oxidant activities were detected among different fractions.
      High-performance liquid chromatography was performed to separate and purify the
      elutions. The compounds were elucidated by 1H, 13C NMR and LCMS. The ethyl
      acetate extract showed maximum inhibitory activity in fungal organisms and Gram
      positive bacteria, and had the highest anti-oxidant capacity. Eight xanthones
      were isolated in ethyl acetate fraction from S. macrosperma. Moreover, compounds
      IV-VI and VIII were isolated from the plant for the first time, and compound VII
      had the strongest anti-oxidant effect.

PMID- 27687567
TI  - Nuf and Rip11 requirement for polarity determinant recycling during Drosophila
      development.
AB  - A tight relationship between apico-basal polarity and trafficking is essential
      for epithelial physiology and tissue homeostasis. Recent studies have described
      how some Rab GTPases, key components of the intracellular traffic machinery,
      contribute to the establishment of cell polarity in vertebrates. We have
      demonstrated a novel connection between cell polarity and trafficking: in
      Drosophila epithelia, the apical determinant aPKC is recycled via Rab11-Nuf
      recycling endosomes to maintain cell polarity. Furthermore, the phosphorylation
      of Nuf by aPKC allows aPKC to control the sub-cellular localization of Nuf and
      its own membrane accumulation. Here we review these data and show the different
      contribution of the 2 Drosophila Rab11 adaptor proteins, Nuf and Rip11, to the
      maintenance of Drosophila embryonic ectoderm polarity.

PMID- 27687568
TI  - Intrauterine fetal death and risk of shoulder dystocia at delivery.
AB  - INTRODUCTION: Vaginal delivery is recommended after intrauterine fetal death.
      However, little is known about the risk of shoulder dystocia in these deliveries.
      We studied whether intrauterine fetal death increases the risk of shoulder
      dystocia at delivery. MATERIAL AND METHODS: In this population-based register
      study using the Medical Birth Registry of Norway, we included all singleton
      pregnancies with vaginal delivery of offspring in cephalic presentation in Norway
      during the period 1967-2012 (n = 2 266 118). Risk of shoulder dystocia was
      estimated as absolute risk (%) and odds ratio with 95% confidence interval.
      Adjustment was made for offspring birthweight (in grams). We performed sub
      analyses within categories of birthweight (<4000 and >=4000 g) and in pregnancies
      with maternal diabetes. RESULTS: Shoulder dystocia occurred in 1.1% of
      pregnancies with intrauterine fetal death and in 0.8% of pregnancies without
      intrauterine fetal death (p < 0.0001) (crude odds ratio 1.5, 95% confidence
      interval 1.2-4.9). After adjustment for birthweight, the odds ratio was 5.9 (95%
      confidence interval 4.7-7.4). In pregnancies with birthweight >=4000 g, shoulder
      dystocia occurred in 14.6% of pregnancies with intrauterine fetal death and in
      2.8% of pregnancies without intrauterine fetal death (p < 0.001) (crude odds
      ratio 5.9, 95% confidence interval 4.5-7.9). In pregnancies with birthweight
      >=4000 g and concurrent maternal diabetes, shoulder dystocia occurred in 57.1% of
      pregnancies with intrauterine fetal death and 9.6% of pregnancies without
      intrauterine fetal death (p < 0.001) (crude odds ratio 12.6, 95% confidence
      interval 5.9-26.9). CONCLUSIONS: Intrauterine fetal death increased the risk of
      shoulder dystocia at delivery, and the absolute risk of shoulder dystocia was
      particularly high if offspring birthweight was high and the mother had diabetes.

PMID- 27687569
TI  - Representing and decomposing genomic structural variants as balanced integer
      flows on sequence graphs.
AB  - BACKGROUND: The study of genomic variation has provided key insights into the
      functional role of mutations. Predominantly, studies have focused on single
      nucleotide variants (SNV), which are relatively easy to detect and can be
      described with rich mathematical models. However, it has been observed that
      genomes are highly plastic, and that whole regions can be moved, removed or
      duplicated in bulk. These structural variants (SV) have been shown to have
      significant impact on phenotype, but their study has been held back by the
      combinatorial complexity of the underlying models. RESULTS: We describe here a
      general model of structural variation that encompasses both balanced
      rearrangements and arbitrary copy-number variants (CNV). CONCLUSIONS: In this
      model, we show that the space of possible evolutionary histories that explain the
      structural differences between any two genomes can be sampled ergodically.

PMID- 27687570
TI  - Weak low-frequency electromagnetic oscillations in water.
AB  - Recent observations of low-frequency electromagnetic oscillations in water
      suggest an inductive structural component. Accordingly, we assume a helical basis
      enabling us to model water as an LC tuned oscillator. A proposed tetrahedral
      structure consisting of three water molecules and one hydronium ion is
      incorporated into the Boerdijk-Coxeter tetrahelix to form long water chains that
      are shown to have resonance frequencies consistent with observation. This model
      also serves to explain separately reported claims of ion cyclotron resonance of
      hydronium ions, in that the tetrahelix provides a built-in path for helical
      proton-hopping.

PMID- 27687571
TI  - Volitional exaggeration of body size through fundamental and formant frequency
      modulation in humans.
AB  - Several mammalian species scale their voice fundamental frequency (F0) and
      formant frequencies in competitive and mating contexts, reducing vocal tract and
      laryngeal allometry thereby exaggerating apparent body size. Although humans'
      rare capacity to volitionally modulate these same frequencies is thought to
      subserve articulated speech, the potential function of voice frequency modulation
      in human nonverbal communication remains largely unexplored. Here, the voices of
      167 men and women from Canada, Cuba, and Poland were recorded in a baseline
      condition and while volitionally imitating a physically small and large body
      size. Modulation of F0, formant spacing (?F), and apparent vocal tract length
      (VTL) were measured using Praat. Our results indicate that men and women
      spontaneously and systemically increased VTL and decreased F0 to imitate a large
      body size, and reduced VTL and increased F0 to imitate small size. These voice
      modulations did not differ substantially across cultures, indicating potentially
      universal sound-size correspondences or anatomical and biomechanical constraints
      on voice modulation. In each culture, men generally modulated their voices
      (particularly formants) more than did women. This latter finding could help to
      explain sexual dimorphism in F0 and formants that is currently unaccounted for by
      sexual dimorphism in human vocal anatomy and body size.

PMID- 27687572
TI  - CRISPR/Cas9 in allergic and immunologic diseases.

PMID- 27687573
TI  - Use of Single-Layer g-C3N4/Ag Hybrids for Surface-Enhanced Raman Scattering
      (SERS).
AB  - Surface-enhanced Raman scattering (SERS) substrates with high activity and
      stability are desirable for SERS sensing. Here, we report a new single atomic
      layer graphitic-C3N4 (S-g-C3N4) and Ag nanoparticles (NPs) hybrid as high
      performance SERS substrates. The SERS mechanism of the highly stable S-g-C3N4/Ag
      substrates was systematically investigated by a combination of experiments and
      theoretical calculations. From the results of XPS and Raman spectroscopies, it
      was found that there was a strong interaction between S-g-C3N4 and Ag NPs, which
      facilitates the uniform distribution of Ag NPs over the edges and surfaces of S-g
      C3N4 nanosheets, and induces a charge transfer from S-g-C3N4 to the oxidizing
      agent through the silver surface, ultimately protecting Ag NPs from oxidation.
      Based on the theoretical calculations, we found that the net surface charge of
      the Ag atoms on the S-g-C3N4/Ag substrates was positive and the Ag NPs presented
      high dispersibility, suggesting that the Ag atoms on the S-g-C3N4/Ag substrates
      were not likely to be oxidized, thereby ensuring the high stability of the S-g
      C3N4/Ag substrate. An understanding of the stability mechanism in this system can
      be helpful for developing other effective SERS substrates with long-term
      stability.

PMID- 27687574
TI  - Plastic microfibre ingestion by deep-sea organisms.
AB  - Plastic waste is a distinctive indicator of the world-wide impact of
      anthropogenic activities. Both macro- and micro-plastics are found in the ocean,
      but as yet little is known about their ultimate fate and their impact on marine
      ecosystems. In this study we present the first evidence that microplastics are
      already becoming integrated into deep-water organisms. By examining organisms
      that live on the deep-sea floor we show that plastic microfibres are ingested and
      internalised by members of at least three major phyla with different feeding
      mechanisms. These results demonstrate that, despite its remote location, the deep
      sea and its fragile habitats are already being exposed to human waste to the
      extent that diverse organisms are ingesting microplastics.

PMID- 27687575
TI  - Hormesis running hot and cold.

PMID- 27687576
TI  - Wideband dynamic microwave frequency identification system using a low-power
      ultracompact silicon photonic chip.
AB  - Photonic-based instantaneous frequency measurement (IFM) of unknown microwave
      signals offers improved flexibility and frequency range as compared with
      electronic solutions. However, no photonic platform has ever demonstrated the key
      capability to perform dynamic IFM, as required in real-world applications. In
      addition, all demonstrations to date employ bulky components or need high optical
      power for operation. Here we demonstrate an integrated photonic IFM system that
      can identify frequency-varying signals in a dynamic manner, without any need for
      fast measurement instrumentation. The system is based on a fully linear,
      ultracompact system based on a waveguide Bragg grating on silicon, only 65-MUm
      long and operating up to ~30 GHz with carrier power below 10 mW, significantly
      outperforming present technologies. These results open a solid path towards
      identification of dynamically changing signals over tens of GHz bandwidths using
      a practical, low-cost on-chip implementation for applications from broadband
      communications to biomedical, astronomy and more.

PMID- 27687577
TI  - Ectopic expression of Cripto-1 in transgenic mouse embryos causes hemorrhages,
      fatal cardiac defects and embryonic lethality.
AB  - Targeted disruption of Cripto-1 in mice caused embryonic lethality at E7.5,
      whereas we unexpectedly found that ectopic Cripto-1 expression in mouse embryos
      also led to embryonic lethality, which prompted us to characterize the causes and
      mechanisms underlying embryonic death due to ectopic Cripto-1 expression.
      RCLG/EIIa-Cre embryos displayed complex phenotypes between embryonic day 14.5
      (E14.5) and E17.5, including fatal hemorrhages (E14.5-E15.5), embryo resorption
      (E14.5-E17.5), pale body surface (E14.5-E16.5) and no abnormal appearance (E14.5
      E16.5). Macroscopic and histological examination revealed that ectopic expression
      of Cripto-1 transgene in RCLG/EIIa-Cre embryos resulted in lethal cardiac
      defects, as evidenced by cardiac malformations, myocardial thinning, failed
      assembly of striated myofibrils and lack of heartbeat. In addition, Cripto-1
      transgene activation beginning after E8.5 also caused the aforementioned lethal
      cardiac defects in mouse embryos. Furthermore, ectopic Cripto-1 expression in
      embryonic hearts reduced the expression of cardiac transcription factors, which
      is at least partially responsible for the aforementioned lethal cardiac defects.
      Our results suggest that hemorrhages and cardiac abnormalities are two important
      lethal factors in Cripto-1 transgenic mice. Taken together, these findings are
      the first to demonstrate that sustained Cripto-1 transgene expression after E11.5
      causes fatal hemorrhages and lethal cardiac defects, leading to embryonic death
      at E14.5-17.5.

PMID- 27687578
TI  - Early CMV-replication after allogeneic stem cell transplantation is associated
      with a reduced relapse risk in lymphoma.
AB  - A preventive effect of early human cytomegalovirus (HCMV) replication was
      evaluated in 136 non-Hodgkin lymphoma (NHL) patients with mature B-cell NHLs (n =
      94), and mature T- and NK-cell NHLs (n = 42) after allogeneic stem cell
      transplantation (alloSCT). Most study-patients (85%) had received at least 2
      cycles of chemotherapy and 60% had also received an autograft prior to alloSCT.
      First detection of CMV-replication by HCMV antigenemia/viremia was found at a
      median of day +33 after alloSCT. The cumulative incidence of relapse at 5 years
      after alloSCT was 38% (95% confidence interval [95%CI]: 26-49) in 82 patients
      without compared to 22% (95%CI: 8-37) in 54 patients with HCMV
      antigenemia/viremia (p = .013). A decreased relapse risk of HCMV replication was
      confirmed by multivariate analysis for HCMV antigenemia/viremia (Hazard ratio
      [HR]: 0.29, 95%CI: 0.11-0.76, p < .014). This report demonstrated a possible
      improvement of relapse incidence after replicative HCMV infection in patients
      with NHL after alloSCT.

PMID- 27687579
TI  - Variants of the elastin (ELN) gene and susceptibility to intracranial aneurysm: a
      synthesis of genetic association studies using a genetic model-free approach.
AB  - BACKGROUND: The presence of an intracranial aneurysm (IA) is thought to have a
      genetic origin. The genetic association studies (GAS) that investigated the
      association between IA and elastin gene (ELN) variants have produced
      contradictory or inconclusive results. MATERIALS AND METHODS: In order to
      decrease the uncertainty of estimated genetic risk effects, a meta-analysis of
      published GAS-related variants in the ELN gene (ELN INT20 1315T > C, EX20 1264G >
      A, INT23 1501 + 24T > C and INT4 196 + 71G > A) with susceptibility to IA was
      conducted using a genetic model-free approach. The risk effects were estimated
      using the generalized odds ratio (ORG) metric. RESULTS: The analysis showed
      significant association for the INT20 1315T > C variant [ORG = 0.66 (0.45-0.95)],
      indicating a protection effect. For the variants EX20 1264G > A, INT23 1501 + 24T
      > C and INT4 196 + 71G > A, no statistically significant association with IAs was
      found. CONCLUSION: There is evidence that the ELN variant INT20 1315T > C is
      implicated in the development of IA; however, the results should be interpreted
      with caution since the number of published studies is limited.

PMID- 27687581
TI  - SOD1 dimerization monitoring using a novel split NanoLuc, NanoBit.
AB  - In the present study, we applied a highly sensitive NanoLuc-based technology to
      understand the status of superoxide dismutase 1 (SOD1) within mammalian cells.
      Two fragments of NanoLuc (NanoBit), large N-terminal and small C-terminal
      regions, were fused with wild-type (wt) and mutant human SOD1 (hSOD1) genes and
      transfected into cells. Luciferase activity through NanoBit assembly was only
      detected in NanoBit-tagged wtSOD1-expressing cells. Furthermore, the developed
      NanoLuc system was used to investigate the role of protein-protein interactions
      in the pathogenesis of amyotrophic lateral sclerosis (ALS). In addition to SOD1,
      we also applied this NanoBit system for detecting the dimerization of wild-type,
      M337V-mutated human TAR-binding protein 43 kDa (hTDP43) and its cleaved C
      terminal fragment (TDP25M337V ) as well as their interactions with SOD1.
      Luciferase activities of NanoBit-tagged mutant SOD1, TDP43, or TDP25 were
      negligible. Finally, we found that a zinc chelator partially reduced the
      luciferase activity of NanoBit-wtSOD1. Collectively, these results show that the
      present assay is sensitive and convenient to appreciate ALS and to develop useful
      agents for the modulation of SOD1 conformation.

PMID- 27687580
TI  - Phototaxis of synthetic microswimmers in optical landscapes.
AB  - Many microorganisms, with phytoplankton and zooplankton as prominent examples,
      display phototactic behaviour, that is, the ability to perform directed motion
      within a light gradient. Here we experimentally demonstrate that sensing of light
      gradients can also be achieved in a system of synthetic photo-activated
      microparticles being exposed to an inhomogeneous laser field. We observe a strong
      orientational response of the particles because of diffusiophoretic torques,
      which in combination with an intensity-dependent particle motility eventually
      leads to phototaxis. Since the aligning torques saturate at high gradients, a
      strongly rectified particle motion is found even in periodic asymmetric intensity
      landscapes. Our results are in excellent agreement with numerical simulations of
      a minimal model and should similarly apply to other particle propulsion
      mechanisms. Because light fields can be easily adjusted in space and time, this
      also allows to extend our approach to dynamical environments.

PMID- 27687582
TI  - First-in-man observation of Talaromyces marneffei-transmission by organ
      transplantation.
AB  - A lung transplant recipient was diagnosed with penicilliosis due to Talaromyces
      marneffei, a fungus endemic in South-East Asia, which was acquired by donor
      transmission. This first case of Talaromyces marneffei-transmission by
      transplantation underscores that current globalisation of travelling necessitates
      increased vigilance for transmission of unusual pathogens in organ recipients.

PMID- 27687584
TI  - Colloidal Nanocrystals Embedded in Macrocrystals: Methods and Applications.
AB  - Colloidal semiconductor nanocrystals have gained substantial interest as
      spectrally tunable and bright fluorophores for color conversion and enrichment
      solids. However, they suffer from limitations in processing their solutions as
      well as efficiency degradation in solid films. As a remedy, embedding them into
      crystalline host matrixes has stepped forward for superior photostability,
      thermal stability, and chemical durability while simultaneously sustaining high
      quantum yields. Here, we review three basic methods for loading the macrocrystals
      with nanocrystals, namely relatively slow direct embedding, as well as
      accelerated methods of vacuum-assisted and liquid-liquid diffusion-assisted
      crystallization. We discuss photophysical properties of the resulting composites
      and present their application in light-emitting diodes as well as their
      utilization for plasmonics and excitonics. Finally, we present a future outlook
      for the science and technology of these materials.

PMID- 27687583
TI  - Endodontic repair in immature dogs' teeth with apical periodontitis: blood clot
      vs plasma rich in growth factors scaffold.
AB  - BACKGROUND/AIM: Different types of scaffolds have been suggested for endodontic
      repair procedures. The aim of this study was to compare the outcome of procedures
      using blood clot vs plasma rich in growth factors (PRGF) scaffold in immature
      teeth with apical periodontitis in dogs. MATERIALS AND METHODS: In this in vivo
      animal study, 20 teeth (30 canals) with open apices were divided into two groups
      (n = 12): (1) blood clot and (2) PRGF. Two positive and negative control groups
      were also selected randomly. After exposing the pulp and inducing periapical
      inflammation by placing a sponge soaked in a suspension of dental plaque, the
      root canals of both groups were flushed with sodium hypochlorite and filled with
      triple antibiotic paste. After 28 days, the antibiotic mixture was removed,
      bleeding was induced through the apical foramen, and mineral trioxide aggregate
      was placed over the blood clot in group one and PRGF scaffold in group two.
      Access cavities were then filled with composite resin. The radiographic and
      histological findings were compared immediately after the procedure, as well as
      after 3 and 6 months of follow-up. RESULTS: There was no statistically
      significant difference between the two experimental groups with regard to the
      radiographic or histological results (P > 0.05). The incidence of healed
      periapical radiolucency was 60% and 53.33% in groups one and two, respectively.
      Apical closure was noted in 60% of samples in both experimental groups. New
      cementum-like tissue formation was detected along the walls of the canals, and
      bone-like islands within the canals were also observed. CONCLUSIONS: Plasma rich
      in growth factors scaffold showed no advantage over blood clots regarding healing
      of the periapical radiolucency, radiographic apical closure and type of the newly
      formed soft and hard tissues.

PMID- 27687585
TI  - Current state of genomic policies in healthcare among EU member states: results
      of a survey of chief medical officers.
AB  - Background: A need for a governance of genomics in healthcare among European
      Union (EU) countries arose during an international meeting of experts on public
      health genomics (PHG). We have conducted a survey on existing national genomic
      policies in healthcare among Chief Medical Officers (CMOs) of the 28 EU member
      states, plus Norway. Methods: A questionnaire was sent to CMOs after a meeting on
      the policy implications of PHG held during the Italian presidency of the Council
      of EU in 2014. The survey was closed in November 2015. Results: CMOs response
      rate was 65.5% (19/29). Twelve (63.2%) reported that their countries had a policy
      for genomics in healthcare in place, and 15 (78.9%) reported that public funding
      existed. Public research facilities for the development of such policies were
      documented in 13 (68.4%) countries, and 15 (83.3%) had working groups devoted to
      policy development. National agencies carrying out Health Technology Assessment
      of genomic-based technologies were present in nine countries (50%). Sixteen
      (88.9%) countries reported having agencies dealing with ethical issues related to
      genomic technologies. About 55% of countries disclosed the lack of information
      campaigns aimed at citizens, and 44.4% reported they had a legal framework for
      direct-to-consumer genetic tests. Conclusion: Belgium, France, Italy, Spain and
      UK documented the presence of a policy on genomics in healthcare. While many
      caveats are necessary because of the methodology, results suggest a need for a co
      ordinated effort to foster development and harmonization of dedicated policies
      across EU to responsibly integrate genomics policies into existing health
      systems.

PMID- 27687587
TI  - Essential and Beneficial Trace Elements in Plants, and Their Transport in Roots:
      a Review.
AB  - The essentiality of 14 mineral elements so far have been reported in plant
      nutrition. Eight of these elements were known as micronutrients due to their
      lower concentrations in plants (usually <=100 mg/kg/dw). However, it is still
      challenging to mention an exact number of plant micronutrients since some
      elements have not been strictly proposed yet either as essential or beneficial.
      Micronutrients participate in very diverse metabolic processes, including from
      the primary and secondary metabolism to the cell defense, and from the signal
      transduction to the gene regulation, energy metabolism, and hormone perception.
      Thus, the attempt to understand the molecular mechanism(s) behind their transport
      has great importance in terms of basic and applied plant sciences. Moreover,
      their deficiency or toxicity also caused serious disease symptoms in plants, even
      plant destruction if not treated, and many people around the world suffer from
      the plant-based dietary deficiencies or metal toxicities. In this sense, shedding
      some light on this issue, the 13 mineral elements (Fe, B, Cu, Mn, Mo, Si, Zn, Ni,
      Cl, Se, Na, Al, and Co), required by plants at trace amounts, has been reviewed
      with the primary focus on the transport proteins (transporters/channels) in plant
      roots. So, providing the compiled but extensive information about the structural
      and functional roles of micronutrient transport genes/proteins in plant roots.

PMID- 27687586
TI  - WNT1 Gene from WNT Signaling Pathway Is a Direct Target of miR-122 in
      Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is an invasive form of hepatic cancer arising from
      the accumulation of multiple genetic alterations. In this study, the causal role
      of disturbed canonical Wnt/beta-catenin pathway was approved, and some of HCC
      driven important gene candidates were determined. MicroRNAs (miRNAs), small non
      coding RNAs, are the key regulators of important cancer genes, and their
      participation in tumorigenesis has been shown. By reviewing literature, WNT1 gene
      with functional significance was selected to approve miRNAs as new subjects for
      targeted therapy.For proper and fast miRNA detection and also confirmation of the
      role of bioinformatics in obtaining practical data, we benefited from different
      bioinformatics tools such as TargetScan, miRanda, and DIANA. In order to use an
      HCC model, we used HepG2 cell line. Luciferase assay was applied to assess the
      ability of the selected miRNAs in targeting WNT1 3'-UTR. To overexpress the
      selected miRNA in HepG2 cell line, viral construct was prepared. Quantitative
      real-time PCR was performed to evaluate selected miRNA and target gene expression
      levels. miR-122 was selected according to data concerning various bioinformatics
      tools.miR-122 was downregulated and WNT1 gene expression was upregulated in HepG2
      cell line. After viral construct transduction, miR-122 expression was elevated
      and WNT1 expression was notably declined. Finally, we introduced WNT1 gene as one
      of the important genes in HCC, and also, we showed that miR-122 can regulate WNT1
      gene expression.Moreover, our study determines the potential of bioinformatics
      analyses in providing accurate and reliable data for miRNA: messenger RNA (mRNA)
      prediction.

PMID- 27687588
TI  - Identification and impact of discoverers in online social systems.
AB  - Understanding the behavior of users in online systems is of essential importance
      for sociology, system design, e-commerce, and beyond. Most existing models assume
      that individuals in diverse systems, ranging from social networks to e-commerce
      platforms, tend to what is already popular. We propose a statistical time-aware
      framework to identify the users who differ from the usual behavior by being
      repeatedly and persistently among the first to collect the items that later
      become hugely popular. Since these users effectively discover future hits, we
      refer them as discoverers. We use the proposed framework to demonstrate that
      discoverers are present in a wide range of real systems. Once identified,
      discoverers can be used to predict the future success of new items. We finally
      introduce a simple network model which reproduces the discovery patterns observed
      in the real data. Our results open the door to quantitative study of detailed
      temporal patterns in social systems.

PMID- 27687589
TI  - Immune adjuvant effect of a Toxoplasma gondii profilin-like protein in autologous
      whole-tumor-cell vaccination in mice.
AB  - Profilin-like protein in Toxoplasma gondii (TgPLP) is a Toll-like receptor (TLR)
      agonist. In this study, we investigated whether TgPLP has an adjuvant effect on
      immune function in autologous whole-tumor-cell vaccine (AWV) treatment. Mice
      vaccinated with AWV together with recombinant TgPLP protein had smaller CT26
      tumors and increased survival. TgPLP treatment strongly increased the production
      of IL-12 through MyD88 signaling and several chemokines, including CCL5, CCL12,
      and XCL1, in bone marrow-derived macrophages (BMMs). In addition, TgPLP increased
      the phagocytosis of tumor cells by BMMs and promoted immune cell mobility on a
      tumor-matrigel scaffold. TgPLP triggered immune responses as demonstrated by
      increased expression of antigen presenting cell markers (MHC class I and II,
      B7.1, and B7.2) in BMMs and increased IL-12 and IFN-gamma expression in mice.
      Mice vaccinated with AWV and TgPLP had more immune cells (CD4+ and CD8+ T cells,
      natural killer cells, and macrophages) in the spleen and higher total IgG and
      IgG2a concentrations in the blood than mice vaccinated with AWV alone. These
      findings suggest that TgPLP is a TLR-based vaccine adjuvant that enhances
      antitumor immune responses during vaccination with AWV.

PMID- 27687590
TI  - Fiber-modified adenovirus-mediated suicide gene therapy can efficiently eliminate
      bladder cancer cells in vitro and in vivo.
AB  - Adenovirus-mediated gene therapy is a promising strategy for bladder cancer
      treatment. However, the loss of the coxsackie and adenovirus receptor (CAR) in
      bladder cancer cells decreases the infection efficiency of the therapeutic
      adenovirus. In this study, we constructed an Arg-Gly-Asp (RGD)-modified
      adenovirus, RGDAd-UPII-TK, that carries a suicide gene called HSV-TK that is
      driven by a human UPII promoter. Then, we tested the bladder cancer specificity
      of the UPII promotor and the expression of the HSV-TK protein. Additionally, we
      observed a potent cytotoxic effects of RGDAd-UPII-TK and ganciclovir (GCV) on
      bladder cancer as demonstrated by reduced cell survival and morphology changes in
      vitro. Furthermore, we confirmed that RGDAd-UPII-TK in combination with a GCV
      injection could significantly reduce the established T24 tumor growth and
      increase apoptosis in vivo. Altogether, our results indicated that the
      recombinant adenovirus RGDAd-UPII-TK could target bladder cancer through valid
      gene therapy.

PMID- 27687591
TI  - MDM4 rs4245739 A > C polymorphism correlates with reduced overall cancer risk in
      a meta-analysis of 69477 subjects.
AB  - Mouse double minute 4 (MDM4) is a p53-interacting oncoprotein that plays an
      important role in the p53 tumor suppressor pathway. The common rs4245739 A > C
      polymorphism creates a miR-191 binding site in the MDM4 gene transcript. Numerous
      studies have investigated the association between this MDM4 polymorphism and
      cancer risk, but have failed to reach a definitive conclusion. To address this
      issue, we conducted a meta-analysis by selecting eligible studies from MEDLINE,
      EMBASE, and Chinese Biomedical databases. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were used to assess the strength of the associations. We also
      performed genotype-based mRNA expression analysis using data from 270 individuals
      retrieved from public datasets. A total of 15 studies with 19796 cases and 49681
      controls were included in the final meta-analysis. The pooled results revealed
      that the MDM4 rs4245739C allele is associated with a decreased cancer risk in the
      heterozygous (AC vs. AA: OR = 0.82, 95% CI = 0.73-0.93), dominant (AC/CC vs. AA:
      OR = 0.82, 95% CI = 0.72-0.93), and allele contrast models (C vs. A: OR = 0.84,
      95% CI = 0.76-0.94). The association was more prominent in Asians and population
      based studies. We also found that the rs4245739C allele was associated with
      decreased MDM4 mRNA expression, especially for Caucasians. Thus the MDM4
      rs4245739 A > C polymorphism appears to be associated with decreased cancer risk.
      These findings would be strengthened by new studies with larger sample sizes and
      encompassing additional ethnicities.

PMID- 27687592
TI  - Correlation of neuroendocrine features with prognosis of non-small cell lung
      cancer.
AB  - The improvement in histological diagnostic tools, including neuroendocrine
      markers by immunohistochemistry (IHC), has led to increased recognition of non
      small cell lung cancer (NSCLC) with neuroendocrine (NE) feature. However, little
      is known regarding the prevalence and clinical implications of NE feature in
      patients with NSCLC. In this study, we performed IHC in a tissue microarray
      containing 451 Chinese NSCLC cases, and analyzed correlation of the expression of
      neuroendocrine marker with pathological and clinical features of NSCLC. The
      result showed that NE feature in NSCLC was detectable in almost 30% of studied
      patients, and tumors with NE feature were significantly correlated with
      pathological classification, clinical stages and cell differentiation of NSCLC.
      Our data also revealed that NE feature indicated worse overall survival and
      disease free survival. Compared with mutant p53, NE markers showed more
      significance as for prognostic evaluation. Multi-factor COX analysis further
      suggested a potential clinical impact for NE feature as an independent indicator
      of poor prognosis for NSCLC patients.

PMID- 27687593
TI  - CARP-1 functional mimetics are novel inhibitors of drug-resistant triple negative
      breast cancers.
AB  - Doxorubicin and Cisplatin are the frontline therapeutics for treatment of the
      triple negative breast cancers (TNBCs). Emergence of drug-resistance often
      contributes to failure of drugs and poor prognosis, and thus necessitates
      development of new and improved modalities to treat TNBCs. We generated and
      characterized chemotherapy-resistant TNBC cells following their culture in
      chronic presence of Doxorubicin or Cisplatin, and tested whether their
      viabilities were inhibited by a novel class of CARP- 1 functional mimetic (CFM)
      compounds. Analogs of parent compound CFM-4 were obtained through structure
      activity based medicinal chemistry studies. CFM-4.16, a novel analog of CFM-4,
      caused superior inhibition of viability of TNBC cells when used in combination
      with doxorubicin. Doxorubicin and cisplatin inhibited viabilities of parental
      cells with GI50 dose of 0.02-0.1 MUM and 1.65 MUM, respectively. The GI50 dose of
      doxorubicin for doxorubicin-resistant TNBC cells was >= 10.0 MUM. For Cisplatin
      resistant cells, the GI50 dose of Cisplatin was >= 6-15.0 MUM for MDA-MB-468
      sublines and >= 150.0 MUM for MDA-MB-231 sublines. CFM-4.16 inhibited viability
      of chemotherapy-resistant TNBC cells, in part by inhibiting oncogenic cMet
      activation and expression, stimulating CARP-1 expression, caspase-8 cleavage and
      apoptosis. CFM-4.16 pretreatment enhanced anti-TNBC efficacies of inhibitors of
      cMET (Tevatinib) or cSrc (Dasatinib). CFM-4.16 suppressed growth of resistant
      TNBC cells in soft agar as well as in three-dimensional suspension cultures
      derived from enriched, stem-like cells. Finally, a nanolipid formulation of CFM
      4.16 in combination with doxorubicin had superior efficacy in inhibiting TNBC
      xenograft growth. Our findings collectively demonstrate therapeutic potential of
      CFM-4.16 for parental and drug-resistant TNBCs.

PMID- 27687596
TI  - Chest pain in the emergency room-an interesting case presentation.
AB  - A 61-year-old woman presented to the emergency room with atypical chest pain, non
      diagnostic electrocardiogram, and an initial troponin level that was normal. A
      coronary computed tomography angio (CCTA) was performed, and on initial review,
      it appeared to be normal. Subsequent review including evaluation of functional
      data from the retrospective scan identified a distal left anterior descending
      occlusion and an apical wall-motion abnormality with no other evidence of heart
      disease. This case illustrates the complementary contribution of anatomic and
      functional data and serves to remind us that on rare occasions, what looks
      "normal" is not always normal.

PMID- 27687595
TI  - Differentiation of five enterohepatic Helicobacter species by nested PCR with
      high-resolution melting curve analysis.
AB  - BACKGROUND: Enterohepatic Helicobacter species (EHS) are widespread in rodent
      species around the world. Several studies have demonstrated that infection with
      EHS can interfere with the outcomes of animal experiments in cancer research and
      significantly influence the study results. Therefore, it is essential to
      establish a rapid detection and identification of EHS for biomedical research
      using laboratory rodents. Our study aimed to develop a rapid and sensitive method
      to detect and distinguish five enterohepatic Helicobacter species. MATERIALS AND
      METHODS: Nested PCR followed by high-resolution melting curve analysis (HRM) was
      developed for identification of H. bilis, H. rodentium, H. muridarum, H.
      typhlonius, as well as H. hepaticus. To validate the accuracy of nested PCR-HRM
      analysis, quantitative real-time PCR methods for five different enterohepatic
      Helicobacter species were developed. A total of 50 cecal samples were tested
      using both nested PCR-HRM analysis and qPCR method. RESULTS: The nested PCR-HRM
      method could distinguish five enterohepatic Helicobacter species by different
      melting temperatures. The melting curve were characterized by peaks of 78.7 +/-
      0.12 degrees C for H. rodentium, 80.51 +/- 0.09 degrees C for H. bilis, 81.6 +/-
      0.1 degrees C for H. typhlonius, 82.11 +/- 0.18 degrees C for H. muridarum, and
      82.95 +/- 0.09 degrees C for H. hepaticus. CONCLUSIONS: The nested PCR-HRM assay
      is a simple, rapid, and cost-effective assay. This assay could be a useful tool
      for molecular epidemiology study of enterohepatic Helicobacter infection and an
      attractive alternative for genotyping of enterohepatic Helicobacter species.

PMID- 27687594
TI  - Role of autophagy and lysosomal drug sequestration in acquired resistance to
      doxorubicin in MCF-7 cells.
AB  - BACKGROUND: The roles and mechanisms involved in starvation-induced autophagy in
      mammalian cells have been extensively studied. However, less is known about the
      potential role for autophagy as a survival pathway in acquired drug resistance in
      cancer cells under nutrient-rich conditions. METHODS: We selected MCF-7 breast
      tumor cells for survival in increasing concentrations of doxorubicin and assessed
      whether the acquisition of doxorubicin resistance was accompanied by changes in
      doxorubicin and lysosome localization and the activation of autophagy, as
      assessed by laser scanning confocal microscopy with or without
      immunohistochemical approaches. The ultrastructure of cells was also viewed using
      transmission electron microscopy. Cellular levels of autophagy and apoptosis
      related proteins were assessed by immunoblotting techniques, while protein
      turnover was quantified using a flux assay. RESULTS: As cells acquired resistance
      to doxorubicin, the subcellular location of the drug moved from the nucleus to
      the perinuclear region. The location of lysosomes and autophagosomes also changed
      from being equally distributed throughout the cytoplasm to co-localizing with
      doxorubicin in the perinuclear region. There was an apparent temporal correlation
      between the acquisition of doxorubicin resistance and autophagy induction, as
      measured by increases in monodansylcadaverine staining, LC3-II production, and co
      localization of LAMP1 and LC3-II immunofluorescence. Electron microscopy revealed
      an increase in cytoplasmic vacuoles containing mitochondria and other cellular
      organelles, also suggestive of autophagy. Consistent with this view, a known
      autophagy inhibitor (chloroquine) was highly effective in restoring doxorubicin
      sensitivity in doxorubicin-resistant cells. Moreover, this induction of autophagy
      correlated temporally with increased expression of the selective cargo receptor
      p62, which facilitates the delivery of doxorubicin-damaged mitochondria and other
      organelles to autophagosomes. Finally, we suggest that autophagy associated with
      doxorubicin resistance may be distinct from classical starvation-induced
      autophagy, since Beclin 1 and Atg7 expression did not change upon acquisition of
      doxorubicin resistance, nor did recombinant Bcl2 overexpression or an Atg7
      knockdown alter doxorubicin cytotoxicity. CONCLUSION: Taken together, our
      findings suggest that doxorubicin resistance in MCF-7 breast cancer cells is
      mediated, at least in part, by the activation of autophagy, which may be distinct
      from starvation-induced autophagy.

PMID- 27687597
TI  - [Pulmonary hypertension: definition, classification and treatments].
AB  - Pulmonary hypertension (PH) is a cardio-pulmonary disorder that may involve
      multiple clinical conditions and can complicate the majority of cardiovascular
      and respiratory diseases. Its definition is an increase in mean pulmonary artery
      pressure (mPAP) ?hbox{$?geqslant $} ? 25 mmHg at rest, leading to right heart
      failure and ultimately death. The clinical classification of pulmonary
      hypertension (PH) categorizes PH into groups which share similar
      pathophysiological and hemodynamic characteristics and treatments. Five groups of
      disorders that cause PH are identified: pulmonary arterial hypertension (Group 1)
      which is a pre-capillary PH, defined by a normal pulmonary artery wedge pressure
      (PAWP) ?hbox{$?leqslant $} ? 15 mmH, due to remodelling of the small pulmonary
      arteries (<500 MUm); pulmonary hypertension due to left heart disease (Group 2)
      which is a post-capillary PH, defined by an increased pulmonary artery wedge
      pressure (PAWP) >15 mmHg; pulmonary hypertension due to chronic lung disease
      and/or hypoxia (Group 3); chronic thrombo-embolic pulmonary hypertension (Group
      4); and pulmonary hypertension due to unclear and/or multifactorial mechanisms
      (Group 5). PAH (PH group 1) can be treated with agents targeting three
      dysfunctional endothelial pathways of PAH: nitric oxide (NO) pathway, endothelin
      1 pathway and prostacyclin pathway. Patients at low or intermediate risk can be
      treated with either initial monotherapy or initial oral combination therapy. In
      patients at high risk initial combination therapy including intravenous
      prostacyclin analogues should be considered. Patients with inadequate clinical
      response to maximum treatment (triple therapy with an intravenous prostacyclin)
      should be assessed for lung transplantation. Despite progresses, PAH remains a
      fatal disease with a 3-year survival rate of 58%. Treatment of group 2, group 3
      and group 5 PH is the treatment of the causal disease and PAH therapeutics are
      not recommended. Treatment of group 4 PH is pulmonary endarteriectomy if patients
      are eligible, otherwise balloon pulmonary angioplasty and/or medical therapy can
      be considered. 

PMID- 27687598
TI  - [Towards new targets for the treatment of pulmonary arterial hypertension :
      Importance of cell-cell communications].
AB  - Pulmonary arterial hypertension (PAH) is a disorder in which mechanical
      obstruction of the pulmonary vascular bed is largely responsible for the rise in
      mean pulmonary arterial pressure (mPAP), resulting in a progressive functional
      decline despite current available therapeutic options. There are multiple
      mechanisms predisposing to and/or promoting the aberrant pulmonary vascular
      remodeling in PAH, and these involve not only altered crosstalk between cells
      within the vascular wall but also sustained inflammation and dysimmunity, cell
      accumulation in the vascular wall and excessive activation of some growth factor
      stimulated signaling pathways, in addition to the interaction of systemic
      hormones, local growth factors, cytokines, and transcription factors.
      Heterozygous germline mutations in the bone morphogenetic protein receptor, type
      2 (BMPR2) gene, a gene encoding a receptor for the transforming growth factor
      (TGF)-beta superfamily, can predispose to the disease. Although the spectrum of
      therapeutic options for PAH has expanded in the last 20 years, available
      therapies remain essentially palliative. Over the past decade, however, a better
      understanding of key regulators of this irreversible remodeling of the pulmonary
      vasculature has been obtained. New and more effective approaches are likely to
      emerge. The present article profiles the innovative research into novel pathways
      and therapeutic targets that may lead to the development of targeted agents in
      PAH. 

PMID- 27687599
TI  - [Pulmonary arterial hypertension, bone marrow, endothelial cell precursors and
      serotonin].
AB  - Serotonin and bone-marrow-derived stem cells participate together in triggering
      pulmonary hypertension. Our work has shown that the absence of 5-HT2B receptors
      generates permanent changes in the composition of the blood and bone-marrow in
      the myeloid lineages, particularly in endothelial cell progenitors. The initial
      functions of 5-HT2B receptors in pulmonary arterial hypertension (PAH) are
      restricted to bone-marrow cells. They contribute to the
      differentiation/proliferation/mobilization of endothelial progenitor cells from
      the bone-marrow. Those bone-marrow-derived cells have a critical role in the
      development of pulmonary hypertension and pulmonary vascular remodeling. These
      data indicate that bone-marrow derived endothelial progenitors play a key role in
      the pathogenesis of PAH and suggest that interactions involving serotonin and
      bone morphogenic protein type 2 receptor (BMPR2) could take place at the level of
      the bone-marrow. 

PMID- 27687600
TI  - [Venoms and medical research].
AB  - Animal venoms are complex chemical cocktails, comprising a wide range of
      biologically active reticulated peptides that target with high selectivity and
      efficacy a variety of enzymes, membrane receptors, ion channels...Venoms can
      therefore be seen as large natural libraries of biologically active molecules
      that are continuously selected and highly refined by the evolution process, up to
      the point where every molecule is endowed with pharmacological properties that
      are highly valuable in the context of human use and drug development. Therefore,
      venom exploration constitutes a prerequisite to drug discovery. However, mass
      spectrometry and transcriptomics via NGS (Next Generation Sequencing) studies
      have shown the presence of up to 1000 peptides in the venom of single species of
      cone snails and spiders. Therefore the global animal venom resource can be seen
      as a collection of more than 50 to 100 000 000 peptides and proteins of which
      only ~5000 are known. That extraordinary "Eldorado" of bio-optimized compounds
      justifies the development of more global and cutting-edge strategies and
      technologies to explore this resource more efficiently than actually. De novo
      developed approaches and recently obtained results will be described. 

PMID- 27687601
TI  - [Amphibian skin as a source of therapeutic peptides].
AB  - The search for new bioactive molecules that could be used in therapeutics is a
      major public health issue, particularly in the treatment of certain diseases such
      as cancer. In this context the exploration of the venom of animals (snakes,
      amphibians, cones, scorpions, insects...) that produce molecules of various
      structures and biological activities, is a very promising direction. Research in
      this area led to the discovery of neuropeptides, hormones, toxins, antimicrobial
      peptides and other extremely potent mediators. These are now used in many areas
      both in fundamental research and in translational research, respectively, to
      understand biochemical and physiological mechanisms, or to use as medical
      diagnostic tools and for therapeutic purposes. Pr. V. Erspamer is the first
      researcher to have shown, in the 1930s, that in addition to biogenic amines and
      alkaloids, granular glands from the skin of amphibians also produced huge amounts
      of peptides with various structures and biological activities. He also showed
      that these peptides had their counterparts, most often in the form of identical
      or similar peptides, in the central nervous system and the gastrointestinal tract
      of mammals. These observations are summarized in the form of a triangle concept
      of "brain-gut-skin" that states that any peptide found in a compartment should be
      present in the other two. In addition, abundance, ease of extraction and
      identification of peptides from amphibian skin make this model a means to search
      for their counterparts in mammals where they are present in minute quantities.
      This approach has two advantages: (i) at the fundamental level, the large peptide
      diversity, ubiquity and multiplicity of functions to which they participate,
      constitute a true chemical library to understand the mechanisms of recognition
      and signal transduction and study the physicochemical basic of the specificity;
      and (ii) in terms of applications, the relative simplicity of these peptides and
      the rise of the production techniques by chemical or recombinant synthesis offer
      an innovative potential for the development of molecules with pharmacological or
      therapeutic purposes. 

PMID- 27687602
TI  - [Ants: a chemical library of anticancer molecules].
AB  - Animal venoms are complex mixtures containing simple organic molecules, proteins,
      peptides, and other bioactive elements with extraordinary biological properties
      associated with their ability to act on a number of molecular receptors in the
      process of incapacitating their target organisms. In such a context, arthropod
      venoms are invaluable sources of bioactive substances, with therapeutic interest
      but the limited availability of some venom such as those from ants, has
      restricted the potential that these biomolecules could represent. We investigated
      for the first time transcriptomic expression from the ant species Tetramorium
      bicarinatum. Four hundred randomly selected clones from cDNA libraries were
      sequenced and a total of 374 expressed sequence tags (ESTs) were generated. Based
      on the results of BLAST searches, these sequences were clustered and assembled
      into 269 contigs. About 72% (269) of these matched BLASTx hits with an
      interesting diversity and unusual abundance of cellular transcripts (48%) related
      to gene and protein expression reflecting the specialization of this tissue. In
      addition, transcripts encoding transposases were relatively highly expressed
      (14%). It may be that transposable elements are present and that their presence
      accounts for some of the variation in venom toxins. About twenty per cent of the
      ESTs were categorized as putative toxins, the major part represented by allergens
      (48% of the total venom toxins) such as pilosulin 5, sol i 3 and Myp p I and II.
      Several contigs encoding enzymes, including zinc-metalloproteases (17%) that are
      likely involved in the processing and activation of venom proteins/peptides, were
      also identified from the library. In addition, a number of sequences (8%) had no
      significant similarity to any known sequence which indicates a potential source
      of for the discovery of new toxins. In order to provide a global insight on the
      transcripts expressed in the venom gland of the Brazilian ant species Tetramorium
      bicarinatum and to unveil the potential of their products, high-throughput
      expressed sequence tags were generated using Illumina paired-end sequencing
      technology. A total of 212 371 758 pairs of quality-filtered, 100-base-pair
      Illumina reads were obtained. The de novo assemblies yielded 36 042 contigs for
      which 27 873 have at least one predicted ORF among which 59.77% produce
      significant hits in the available databases. The investigation of the read
      mapping toxin class revealed and confirmed a high diversification with the major
      part consistent with the classical hymenopteran venom protein signature
      represented by venom allergen (33.3%) followed by a diverse toxin-expression
      profile including several distinct isoforms of phospholipase A1 and A2, venom
      serine protease, hyaluronidase, protease inhibitor and secapin. Moreover, our
      results revealed for the first time the presence of toxin-like peptides that have
      been previously identified from unrelated venomous animals such as waprin-like
      (snakes) and agatoxins (spiders and conus). These studies provide a first insight
      of the gene expression scenario of the venom gland of T. bicarinatum which might
      contribute to acquiring a more comprehensive view about the origin and functional
      diversity of venom proteins of this ant. Based on such results, we conducted
      cytotoxic tests from the crude venom of T.bicarinatum ant and reported toxic
      effect on tumoral cells lines from one of the fifth of the most frequently
      occurring cancers with a 3-year survival rate of only 30%. In such a context, new
      therapeutic strategies are essential and the discovery of new molecules in ant
      venom could be one possible avenue. Thus our project aims to characterize, from
      the crude venom of T.bicarinatum, the molecule(s) which have potential anti
      cancerous toxicity as well as their mechanisms of action. 

PMID- 27687603
TI  - Endothelial Cells Require CD98 for Efficient Angiogenesis-Brief Report.
AB  - OBJECTIVE: CD98 regulates integrin signaling and is critical for tumor cell
      proliferation. It is also expressed on endothelial cells (EC), but its role in
      angiogenesis is unclear. APPROACH AND RESULTS: We used specific genetic targeting
      and antibody blockade approaches to examine the function of CD98 in EC
      proliferation, blood vessel growth, and tumor angiogenesis. It is upregulated on
      angiogenic ECs, and EC-specific deletion of CD98 in mice inhibited tumor growth,
      retinal angiogenesis, and EC proliferation. Reconstitution with CD98 mutants
      showed that integrin and CD98 interaction is necessary for EC survival and
      growth. Moreover, anti-CD98 treatment inhibited vessel formation and reversed EC
      assisted tumor growth. CONCLUSIONS: Our findings demonstrate a requirement for
      CD98 in EC growth and suggest that CD98-specific reagents could have a dual
      anticancer effect: directly by inhibiting tumor cell proliferation and indirectly
      by preventing tumor angiogenesis.

PMID- 27687606
TI  - Monitoring stress among internal medicine residents: an experience-driven,
      practical and short measure.
AB  - Residents experience severely high levels of stress, depression and burnout,
      leading to perceived medical errors, as well as to symptoms of impairment, such
      as chronic anger, cognitive impairment, suicidal behavior and substance abuse.
      Because research has not yet provided a psychometrically robust population
      specific tool to measure the level of stress of medicine residents, we aimed at
      building and validating such a measure. Using an inductive scale development
      approach, a short, pragmatic measure was built, based on the interviews of 17
      medicine residents. The Internal Medicine Residency Stress Scale (IMRSS) was then
      administered in a sample of 259 internal medicine residents (199 females, 60
      males, MAge = 25.6) along with the Hospital Anxiety and Depression Scale, Maslach
      Burnout Inventory, Satisfaction With Life Scale and Ways of Coping Checklist. The
      IMRSS showed satisfactory internal reliability (Cronbach's alpha = .86), adequate
      structural validity - studied through Confirmatory Factor Analysis (chi2/df =
      2.51, CFI = .94; SRMR = .037, RMSEA = .076) - and good criterion validity - the
      IMRSS was notably strongly correlated with emotional exhaustion (r = .64; p <
      .001) and anxiety (r = .57; p < .001). Because of its short length and robust
      psychometric qualities, the use of the IMRSS is recommended to quickly and
      frequently assess and monitor stress among internal medicine residents.

PMID- 27687604
TI  - Is High-Density Lipoprotein Cholesterol Causally Related to Kidney Function?
      Evidence From Genetic Epidemiological Studies.
AB  - OBJECTIVE: A recent observational study with almost 2 million men reported an
      association between low high-density lipoprotein (HDL) cholesterol and worse
      kidney function. The causality of this association would be strongly supported if
      genetic variants associated with HDL cholesterol were also associated with kidney
      function. APPROACH AND RESULTS: We used 68 genetic variants (single-nucleotide
      polymorphisms [SNPs]) associated with HDL cholesterol in genome-wide association
      studies including >188 000 subjects and tested their association with estimated
      glomerular filtration rate (eGFR) using summary statistics from another genome
      wide association studies meta-analysis of kidney function including <=133 413
      subjects. Fourteen of the 68 SNPs (21%) had a P value <0.05 compared with the 5%
      expected by chance (Binomial test P=5.8*10-6). After Bonferroni correction, 6
      SNPs were still significantly associated with eGFR. The genetic variants with the
      strongest associations with HDL cholesterol concentrations were not the same as
      those with the strongest association with kidney function and vice versa. An
      evaluation of pleiotropy indicated that the effects of the HDL-associated SNPs on
      eGFR were not mediated by HDL cholesterol. In addition, we performed a Mendelian
      randomization analysis. This analysis revealed a positive but nonsignificant
      causal effect of HDL cholesterol-increasing variants on eGFR. CONCLUSIONS: In
      summary, our findings indicate that HDL cholesterol does not causally influence
      eGFR and propose pleiotropic effects on eGFR for some HDL cholesterol-associated
      SNPs. This may cause the observed association by mechanisms other than the mere
      HDL cholesterol concentration.

PMID- 27687608
TI  - Link between prescribing and gifting of educational materials should be studied.

PMID- 27687605
TI  - Local Matrix Metalloproteinase 9 Level Determines Early Clinical Presentation of
      ST-Segment-Elevation Myocardial Infarction.
AB  - OBJECTIVE: Early clinical presentation of ST-segment-elevation myocardial
      infarction (STEMI) and non-ST-segment-elevation myocardial infarction affects
      patient management. Although local inflammatory activities are involved in the
      onset of MI, little is known about their impact on early clinical presentation.
      This study aimed to investigate whether local inflammatory activities affect
      early clinical presentation. APPROACH AND RESULTS: This study comprised 94 and 17
      patients with MI (STEMI, 69; non-STEMI, 25) and stable angina pectoris,
      respectively. We simultaneously investigated the culprit lesion morphologies
      using optical coherence tomography and inflammatory activities assessed by
      shedding matrix metalloproteinase 9 (MMP-9) and myeloperoxidase into the coronary
      circulation before and after stenting. Prevalence of plaque rupture, thin-cap
      fibroatheroma, and lipid arc or macrophage count was higher in patients with
      STEMI and non-STEMI than in those with stable angina pectoris. Red thrombus was
      frequently observed in STEMI compared with others. Local MMP-9 levels were
      significantly higher than systemic levels (systemic, 42.0 [27.9-73.2] ng/mL
      versus prestent local, 69.1 [32.2-152.3] ng/mL versus poststent local, 68.0 [35.6
      133.3] ng/mL; P<0.01). Poststent local MMP-9 level was significantly elevated in
      patients with STEMI (STEMI, 109.9 [54.5-197.8] ng/mL versus non-STEMI: 52.9 [33.0
      79.5] ng/mL; stable angina pectoris, 28.3 [14.2-40.0] ng/mL; P<0.01), whereas no
      difference was observed in the myeloperoxidase level. Poststent local MMP-9 and
      the presence of red thrombus are the independent determinants for STEMI in
      multivariate analysis. CONCLUSIONS: Local MMP-9 level could determine the early
      clinical presentation in patients with MI. Local inflammatory activity for
      atherosclerosis needs increased attention.

PMID- 27687607
TI  - The Identification and Quantification of Suberin Monomers of Root and Tuber
      Periderm from Potato (Solanum tuberosum) as Fatty Acyl tert-Butyldimethylsilyl
      Derivatives.
AB  - INTRODUCTION: Protective plant lipophilic barriers such as suberin and cutin,
      with their associated waxes, are complex fatty acyl derived polyesters. Their
      precise chemical composition is valuable to understand the specific role of each
      compound to the physiological function of the barrier. OBJECTIVES: To develop a
      method for the compositional analysis of suberin and associated waxes by gas
      chromatography (GC) coupled to ion trap-mass spectrometry (IT-MS) using N-(tert
      butyldimethylsilyl)-N-methyl-trifluoroacetamide (MTBSTFA) as sylilating reagent,
      and apply it to compare the suberin of the root and tuber periderm of potato
      (Solanum tuberosum). METHODOLOGY: Waxes and suberin monomers from root and
      periderm were extracted subsequently using organic solvents and by methanolysis,
      and subjected to MTBSTFA derivatisation. GC analyses of periderm extracts were
      used to optimise the chromatographic method and the compound identification.
      Quantitative data was obtained using external calibration curves. The method was
      fully validated and applied for suberin composition analyses of roots and
      periderm. RESULTS: Wax and suberin compounds were successfully separated and
      compound identification was based on the specific (M-57) and non-specific ions in
      mass spectra. The use of calibration curves built with different external
      standards provided quantitative accurate data and showed that suberin from root
      contains shorter chained fatty acyl derivatives and a relative predominance of
      alpha,omega-alkanedioic acids compared to that of the periderm. CONCLUSION: We
      present a method for the analysis of suberin and their associated waxes based on
      MTBSTFA derivatisation. Moreover, the characteristic root suberin composition may
      be the adaptive response to its specific regulation of permeability to water and
      gases. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27687609
TI  - Maltitol inhibits small intestinal glucose absorption and increases insulin
      mediated muscle glucose uptake ex vivo but not in normal and type 2 diabetic
      rats.
AB  - This study investigated the effects of maltitol on intestinal glucose absorption
      and muscle glucose uptake using ex vivo and in vivo experimental models. The ex
      vivo experiment was conducted in isolated jejunum and psoas muscle from normal
      rats. The in vivo study investigated the effects of a single bolus dose of
      maltitol on gastric emptying, intestinal glucose absorption and digesta transit
      in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in
      isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in
      the presence of insulin but not in the absence of insulin. In contrast, maltitol
      did not significantly (p > 0.05) alter small intestinal glucose absorption or
      blood glucose levels as well as gastric emptying and digesta transit in normal or
      type 2 diabetic rats. The results suggest that maltitol may not be a suitable
      dietary supplement for anti-diabetic food and food products to improve glycemic
      control.

PMID- 27687610
TI  - Engineering Halomonas spp. as A Low-Cost Production Host for Production of Bio
      surfactant Protein PhaP.
AB  - Halomonas spp. have been studied as a low cost production host for producing bulk
      materials such as polyhydroxyalkanoates (PHA) bioplastics, since they are able to
      grow at high pH and high NaCl concentration under unsterile and continuous
      conditions without microbial contamination. In this paper, Halomonas strain TD is
      used as a host to produce a protein named PHA phasin or PhaP which has a
      potential to be developed into a bio-surfactant. Four Halomonas TD expression
      strains are constructed based on a strong T7-family expression system. Of these,
      the strain with phaC deletion and chromosomal expression system resulted in the
      highest production of PhaP in soluble form, reaching 19% of total cellular
      soluble proteins and with a yield of 1.86 g/L in an open fed-batch fermentation
      process. A simple "heat lysis and salt precipitation" method is applied to allow
      rapid PhaP purification from a mixture of cellular proteins with a PhaP recovery
      rate of 63%. It clearly demonstrated that Halomonas TD could be used for high
      yield expression of a bio-surfactant protein PhaP for industrial application in
      an economical way.

PMID- 27687612
TI  - Assessing developmental delay in early childhood - concerns with the Bayley-III
      scales.
AB  - OBJECTIVE: Early detection of children with developmental delay is crucial for
      determining which children require close surveillance and intervention services.
      For many decades, the Bayley Scales has been the most widely used objective
      measure of early developmental delay, both in clinical and research settings.
      Significant structural changes were incorporated in the most recent edition, the
      Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). This
      article reviews the psychometric properties of the Bayley-III and investigates
      criticisms raised on the Bayley-III, namely that it overestimates developmental
      status and is a poor predictor of later functioning. METHOD: This critical review
      examines the literature on the Bayley-III, which was released in 2006. RESULTS:
      The Cognitive, Language, and Motor composites of the Bayley-III overestimate
      development, resulting in an under-identification of children with developmental
      delay. A range of strategies have been proposed for dealing with the inflated
      scores on the Bayley-III, none of which are ideal. Evidence to date suggests that
      the Bayley-III is a poor predictor of later cognitive and motor impairments.
      CONCLUSIONS: The Bayley-III needs new norms, or alternatively, it may be time for
      a new edition of the Bayley Scales.

PMID- 27687611
TI  - A synthesis of recent analyses of human resources for health requirements and
      labour market dynamics in high-income OECD countries.
AB  - BACKGROUND: Recognition of the importance of effective human resources for health
      (HRH) planning is evident in efforts by the World Health Organization (WHO) and
      the Global Health Workforce Alliance (GHWA) to facilitate, with partner
      organizations, the development of a global HRH strategy for the period 2016-2030.
      As part of efforts to inform the development of this strategy, the aims of this
      study, the first of a pair, were (a) to conduct a rapid review of recent analyses
      of HRH requirements and labour market dynamics in high-income countries who are
      members of the Organisation for Economic Co-operation and Development (OECD) and
      (b) to identify a methodology to determine future HRH requirements for these
      countries. METHODS: A systematic search of peer-reviewed literature, targeted
      website searches, and multi-stage reference mining were conducted. To supplement
      these efforts, an international Advisory Group provided additional potentially
      relevant documents. All documents were assessed against predefined inclusion
      criteria and reviewed using a standardized data extraction tool. RESULTS: In
      total, 224 documents were included in the review. The HRH supply in the included
      countries is generally expected to grow, but it is not clear whether that growth
      will be adequate to meet health care system objectives in the future. Several
      recurring themes regarding factors of importance in HRH planning were evident
      across the documents reviewed, such as aging populations and health workforces as
      well as changes in disease patterns, models of care delivery, scopes of practice,
      and technologies in health care. However, the most common HRH planning approaches
      found through the review do not account for most of these factors. CONCLUSIONS:
      The current evidence base on HRH labour markets in high-income OECD countries,
      although large and growing, does not provide a clear picture of the expected
      future HRH situation in these countries. Rather than HRH planning methods and
      analyses being guided by explicit HRH policy questions, most of the reviewed
      studies appeared to derive HRH policy questions based on predetermined planning
      methods. Informed by the findings of this review, a methodology to estimate
      future HRH requirements for these countries is described.

PMID- 27687613
TI  - BMI independently relates to glycaemia in patients with severe enduring mental
      illness (SMI).
AB  - BACKGROUND: People with severe mental illness (SMI) have higher rates of diabetes
      than the general population. AIMS: To assess the type-2 diabetes screening rates
      in primary care and the relation between body mass index (BMI) and dysglycaemia
      for patients on the SMI register in the Cheshire region of the United Kingdom.
      METHODS: The setting was 24 general practices in Central and Eastern Cheshire,
      United Kingdom. Subjects were identified through a semianonymized search of GP
      registers. RESULTS: About 451 of the 787 SMI patients were screened for
      dysglycaemia and dyslipidaemia. Fasting glucose was in the impaired fasting
      glycaemia range (6.1-6.9 mmol/l) in 6.5%, and indicative of type-2 diabetes
      (>=7.0 mmol/l) in 17.3%. There was a positive univariate relation between BMI and
      fasting glucose (normalized beta = 0.26, p < 0.001). In multivariate models,
      adjusting for age, gender, smoking and blood pressure, each unit increase in BMI
      [OR = 1.07 (1.01, 1.13); p = 0.031] and triglycerides [OR = 1.28 (1.06, 1.55); p
      = 0.009] were independently associated with an increased risk of having type-2
      diabetes. CONCLUSION: Increasing BMI relates to dysglycaemia in patients with
      severe enduring mental illness (SMI). All patients with SMI whether or not
      receiving neuroleptic treatment should undergo routine monitoring of weight and
      metabolic parameters.

PMID- 27687614
TI  - Patient-reported long-term outcome after primary hypospadias repair.
AB  - PURPOSE: Long-term evaluation of the surgical outcome after puberty, particularly
      patient reported outcome is rare in the literature. The aims of this study were
      to investigation the patients' satisfaction with the long-term results and their
      views and memories of their childhood surgery and follow-up. METHODS: A modified
      version of previously used questionnaire was sent to 134 patients ages 18 years
      or older previously primarily repaired due to hypospadias by one of the authors
      (HS) between 1989 -2009. RESULTS: Thirty-nine patients responded. Eighty-two per
      cent were satisfied with the appearance of their penis, 87% were satisfied with
      their ability to urinate and their sexual function and 92% were satisfied with
      the overall surgical results. Ninety per cent of patients were positive to the
      current duration of our post-pubertal follow-up program or would have preferred
      an even longer follow-up. CONCLUSIONS: The majority of patients were satisfied
      with the long-term surgical results and the duration of follow-up. Despite having
      problems patients does not always contact the health care system spontaneously,
      which warrants long-term follow-up.

PMID- 27687615
TI  - Identification of Undiagnosed Hyperlipidemia: Do Work Site Screening Programs
      Work?
AB  - PURPOSE: We evaluated the rate of hyperlipidemia identified during workplace
      screening in previously undiagnosed individuals, the association between
      workplace hyperlipidemia screening and use of medical care during follow-up, and
      changes in lipid profile among individuals with hyperlipidemia at screening.
      DESIGN: Nonexperimental longitudinal study. SETTING: Employees who participated
      in a workplace health screening. PARTICIPANTS: A total of 18 993 individuals from
      39 self-insured employers in the United States. MEASURES: Total cholesterol, low
      density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were
      measured during screening. A claims-based algorithm was used to identify
      hyperlipidemia cases. ANALYSIS: Discrete-time survival analysis was used to
      estimate monthly rates of new hyperlipidemia diagnoses or prescriptions. Paired t
      tests were used to evaluate 1-year changes in lipid profile. RESULTS: A total of
      1872 (9.9%) individuals had hyperlipidemia at screening. Among all individuals, a
      significantly greater rate of new hyperlipidemia diagnoses was observed during
      the first month after screening, compared to the 3 months before screening (odds
      ratio [95% CI]: 2.99 [2.66-3.36]). Among the 987 individuals who were followed up
      1 year later, significant improvements were observed in total cholesterol (-8.5%
      +/- 13.6%) and LDL levels (-10.2% +/- 19.3%). CONCLUSION: Workplace health
      screenings in an insured population were associated with a subsequent increase in
      physician visits and prescriptions for hyperlipidemia. After 1 year, significant
      improvements in total cholesterol and LDL levels were observed among individuals
      who screened positive for hyperlipidemia.

PMID- 27687616
TI  - Why Has the Health-Promoting Prison Concept Failed to Translate to the United
      States?
AB  - Two decades since the World Health Organization Regional Office for Europe
      published a report on health promotion in prison that stimulated further debate
      on the concept of the "health-promoting prison," this article discusses the
      extent to which the concept has translated to the United States. One predicted
      indicator of success for the health-promoting prison movement was the expansion
      of activity beyond European borders; yet 2 decades since the European model was
      put forward, there has been very limited activity in the United States. This
      "Critical Issues and Trends" article suggests reasons why this translation has
      failed to occur.

PMID- 27687617
TI  - An Empirical Analysis of the Association Between Cigarette Smoking and
      Participation in the Supplemental Nutrition Assistance Program.
AB  - PURPOSE: To examine the association between smoking and participation in
      Supplemental Nutrition Assistance Program (SNAP) among low-income families.
      DESIGN: A quasi-experimental design using pooled cross-sectional data from the
      Bureau of Labor Statistics' Consumer Expenditure Diary Survey. SETTING: A
      national, representative sample of US households from 2005 through 2012.
      PARTICIPANTS: A total of 19 395 low-income households. MEASURES: US poverty
      thresholds were used, in conjunction with household income, to create a sample of
      families at 130% of the federal poverty level and below. Expenditures on
      cigarettes and self-reported enrollment in SNAP were used to measure smoking
      behavior and program participation, respectively. ANALYSIS: Estimation of a
      maximum likelihood model was used to predict the probability of smoking given
      participation in SNAP. RESULTS: The SNAP participation among low-income
      households was associated with a 30% ( P < .01) increase in the likelihood of a
      household containing at least 1 smoker, relative to low-income non-SNAP
      households. Among smokers, SNAP households do not spend more money on tobacco
      products than non-SNAP households. CONCLUSION: Given the strong association found
      between SNAP participation and smoking, connecting program participants who smoke
      to effective smoking cessation programs could be an effective tool in reducing
      the prevalence of smoking among the low-income population. States have a unique
      opportunity to use SNAP-Education programs to integrate tobacco prevention and
      cessation into curriculum for direct client impact.

PMID- 27687618
TI  - A Pilot Study of Healthy Living Options at 16 Truck Stops Across the United
      States.
AB  - PURPOSE: There is a growing body of evidence that the built environment
      influences diet and exercise and, as a consequence, community health status.
      Since long-haul truck drivers spend long periods of time at truck stops, it is
      important to know if this built environment includes resources that contribute to
      the emotional and physical well-being of drivers. SETTING: The truck stop
      environment was defined as the truck stop itself, grocery stores, and medical
      clinics near the truck stop that could be accessed by a large truck or safely on
      foot. DESIGN: Researchers at the National Institute for Occupational Safety and
      Health (NIOSH) developed and utilized a checklist to record the availability of
      resources for personal hygiene and comfort, communication and mental stimulation,
      health care, safety, physical activity, and nutrition at truck stops. SUBJECTS:
      The NIOSH checklist was used to collect data at a convenience sample of 16 truck
      stops throughout the United States along both high-flow and low-flow truck
      traffic routes. MEASURES: The checklist was completed by observation within and
      around the truck stops. RESULTS: No truck stops offered exercise facilities, 94%
      lacked access to health care, 81% lacked a walking path, 50% lacked fresh fruit,
      and 37% lacked fresh vegetables in their restaurant or convenience store.
      CONCLUSION: The NIOSH found that most truck stops did not provide an overall
      healthy living environment.

PMID- 27687619
TI  - Comparing State Legislative Aides' Perspectives on Tobacco Policymaking in States
      With Strong and Weak Policies: A Qualitative Study.
AB  - PURPOSE: The study compared perceptions of state legislative aides about tobacco
      policymaking in states with strong and weak tobacco control policies. APPROACH:
      Qualitative in-depth interviews carried out in 2009. SETTING: The US states were
      ranked on a combination of tobacco prevention funding, taxes, and presence of
      smoke-free policies. States at the top and bottom of the rankings were chosen.
      PARTICIPANTS: Interviews were conducted with 10 legislative aides in 5 states
      with strong tobacco control policies and 10 aides in 7 states with weak policies.
      METHOD: Twenty semistructured interviews were conducted, coded, and analyzed
      using a consensus coding process. RESULTS: Tobacco control was a lower priority
      in states with weak policies, and respondents from these states listed more
      barriers to tobacco control policymaking than those from states with strong
      policies. Successful arguments for tobacco control emphasized operational
      applications, for example, enhanced revenue from tobacco taxes or safety of
      children and employees. CONCLUSION: Our findings support propositions posited in
      the Advocacy Coalition Framework. They point to the preeminence of contextual
      factors, notably political leanings and economic climate on success of policy
      change efforts. Lessons learned from participants from states with strong policy
      nonetheless show promise for success in states with weak policy.

PMID- 27687620
TI  - Assessment of dietary intake of children with chronic kidney disease.
AB  - OBJECTIVE: Our aim was to characterize the nutrient intake of children with
      chronic kidney disease (CKD) relative to recommended intake levels. METHODS: We
      conducted a cross-sectional study of dietary intake assessed by Food Frequency
      Questionnaire (FFQ) in The North American Chronic Kidney Disease in Children
      (CKiD) prospective cohort study. Nutrient intake was analyzed to estimate the
      daily consumption levels of various nutrients and compared with national
      guidelines for intake. RESULTS: There were 658 FFQs available for analysis; 69.9
      % of respondents were boys, with a median age [Interquartile range (IQR)] of 11
      years (8-15). Median daily sodium, potassium, and phosphorus intake was 3089 mg
      (2294-4243), 2384 mg (1804-3076), and 1206 mg (894-1612) respectively. Sodium and
      phosphorus consumptions were higher than recommended in all age groups. Caloric
      intake decreased with dropping glomerular filtration rate (GFR) (p = 0.003). The
      median daily caloric intakes were 1307 kcal in male children 2-3 years old, 1875
      kcal in children 4-8 years old, 1923 kcal in those 9-13 years old, and 2427 kcal
      in those 14-18 years old. Respective levels for girls were 1467 kcal, 1736 kcal,
      1803 kcal, and 2281 kcal. Median protein intake exceeded recommended levels in
      all age groups, particularly among younger participants. Younger children were
      more likely than older children to exceed the recommended intakes for phosphorus
      (p < 0.001) and the age-specific recommended caloric intake (p < 0.001).
      Macronutrient distribution (carbohydrate:fat:protein) was consistent with
      recommendation. CONCLUSIONS: Children in the CKiD cohort consumed more sodium,
      phosphorus, protein, and calories than recommended. The gap between actual
      consumption and recommendations indicates a need for improved nutritional
      counseling and monitoring.

PMID- 27687621
TI  - Ofatumumab in two pediatric nephrotic syndrome patients allergic to rituximab.
AB  - BACKGROUND: Rituximab, a chimeric anti-CD20 monoclonal antibody, is an effective
      treatment in steroid-dependent nephrotic syndrome (SDNS). However, some patients
      develop adverse reactions. CASE-DIAGNOSIS/TREATMENT: Patient 1, a 14-year-old boy
      with SDNS since the age of 2, was treated with oral prednisone, cyclosporine A
      (CsA) and mycophenolate mofetil. A first infusion of rituximab at age 12 years
      was well tolerated, but this was followed by a prolonged relapse unresponsive to
      oral prednisone, mycophenolate mofetil and CsA. A second rituximab infusion was
      attempted, but treatment was interrupted due to severe dyspnea. Treatment with a
      humanized anti-CD20 monoclonal antibody, ofatumumab, was then attempted. The
      patient experienced a mild allergic reaction and maintained remission despite
      interruption of all treatment at >12 months of follow-up. Patient 2, a 3-year-old
      boy who presented at 18 months with nephrotic syndrome initially resistant to
      treatment with oral prednisone, was given with three intravenous boluses of
      methylprednisolone followed by CsA and achieved remission. Upon steroid
      discontinuation, the NS relapsed. Prednisone was restarted and treatment with a
      single dose of rituximab was never completed due to a severe allergic reaction.
      Ofatumumab infusion was uneventful, and he maintained remission during the follow
      up period (>12 months) despite interruption of prednisone therapy. B cells
      reappeared at 7 months in both patients. CONCLUSIONS: Ofatumumab may be a
      therapeutic option in severe forms of NS with allergy to rituximab.

PMID- 27687623
TI  - Preoperative 6-minute walk distance accurately predicts postoperative
      complications after operations for hepato-pancreato-biliary cancer.
AB  - BACKGROUND: Operation for hepato-pancreato-biliary cancer is among the most
      invasive open abdominal operations, with a high postoperative morbidity and
      mortality rate. The purpose of the present study is to investigate whether a
      preoperative 6-minute walk distance can predict major postoperative complications
      after operation for hepato-pancreato-biliary diseases. METHODS: A total of 81
      participants who underwent pancreaticoduodenectomy, major hepatectomy with
      extrahepatic bile duct resection, or hepatopancreatoduodenectomy were included.
      The 6-minute walk distance was performed within 1 week before operation. Patients
      were categorized into 2 groups based on surgical complications: Clavien-Dindo
      grade <3 and Clavien-Dindo grade >=3. Clinical differences between the 2 groups
      were analyzed. Multivariate logistic regression analysis was performed to
      identify risk factors for postoperative complications that were categorized as
      Clavien-Dindo grade >=3. RESULTS: The multiple logistic regression model revealed
      a significant correlation between major postoperative complications and
      preoperative low 6-minute walk distance, low body mass index, and major blood
      loss. In patients with 6-minute walk distance <400 m (1,312 feet), the Clavien
      Dindo grade was considerably greater than patients with >=400 m. CONCLUSION: The
      6-minute walk distance is useful in identifying patients with a greater chance of
      developing major postoperative complications after surgery for hepato-pancreato
      biliary cancer.

PMID- 27687622
TI  - Statin derivatives as therapeutic agents for castration-resistant prostate
      cancer.
AB  - Despite recent advances in modern medicine, castration-resistant prostate cancer
      remains an incurable disease. Subpopulations of prostate cancer cells develop
      castration-resistance by obtaining the complete steroidogenic ability to
      synthesize androgens from cholesterol. Statin derivatives, such as simvastatin,
      inhibit cholesterol biosynthesis and may reduce prostate cancer incidence as well
      as progression to advanced, metastatic phenotype. In this study, we demonstrate
      novel simvastatin-related molecules SVA, AM1, and AM2 suppress the tumorigenicity
      of prostate cancer cell lines including androgen receptor-positive LNCaP C-81 and
      VCaP as well as androgen receptor-negative PC-3 and DU145. This is achieved
      through inhibition of cell proliferation, colony formation, and migration as well
      as induction of S-phase cell-cycle arrest and apoptosis. While the compounds
      effectively block androgen receptor signaling, their mechanism of inhibition also
      includes suppression of the AKT pathway, in part, through disruption of the
      plasma membrane. SVA also possess an added effect on cell growth inhibition when
      combined with docetaxel. In summary, of the compounds studied, SVA is the most
      potent inhibitor of prostate cancer cell tumorigenicity, demonstrating its
      potential as a promising therapeutic agent for castration-resistant prostate
      cancer.

PMID- 27687625
TI  - Introduction to the Special Section.

PMID- 27687624
TI  - Reproducibility of locus coeruleus and substantia nigra imaging with neuromelanin
      sensitive MRI.
AB  - OBJECTIVES: The purpose of this study was to assess the reproducibility of
      substantia nigra pars compacta (SNpc) and locus coeruleus (LC) delineation and
      measurement with neuromelanin-sensitive MRI. MATERIALS AND METHODS: Eleven
      subjects underwent two neuromelanin-sensitive MRI scans. SNpc and LC volumes were
      extracted for each scan. Reproducibility of volume and magnetization transfer
      contrast measurements in SNpc and LC was assessed using intraclass correlation
      coefficients (ICC) and dice similarity coefficients (DSC). RESULTS: SNpc and LC
      volume measurements showed excellent reproducibility (SNpc-ICC: 0.94, p < 0.001;
      LC-ICC: 0.96, p < 0.001). SNpc and LC were accurately delineated between scans
      (SNpc-DSC: 0.80 +/- 0.03; LC-DSC: 0.63 +/- 0.07). CONCLUSION: Neuromelanin
      sensitive MRI can consistently delineate SNpc and LC.

PMID- 27687626
TI  - A study of tumor heterogeneity in a case with breast cancer.
AB  - Tumor heterogeneity has been suggested based on clinical and pathological
      findings. Several clinical findings can be explained by tumor evolution during
      progression and metastasis. We herein report a case of metastatic breast cancer
      indicated tumor heterogeneity by clinical findings and a genomic analysis. A 64
      year-old woman with advanced breast cancer was treated with primary chemotherapy,
      to which primary tumor responded. After a 6 month treatment pause, lung, liver,
      and skin metastases developed and her serum tumor markers were elevated. None of
      those serum markers had been elevated before the treatment, despite the large
      tumor burden. Notably, there was discordance in the expression of human epidermal
      growth factor receptor 2 (HER2) between the primary tumor and metastatic skin
      lesions, with the former being negative and the latter positive. A genomic
      analysis was performed by in-house Breast Cancer Panel, which consisted of 53 pre
      selected genes. Twenty-three somatic mutations were found in primary breast tumor
      and 7 in the skin metastasis. None of these 30 genes matched. However, the cell
      free (cf) DNA in the plasma taken at the time of skin metastasis contained 10
      mutations, 7 from the primary lesion and 3 from the metastasis. These data
      indicate that the clonal changes or tumor heterogeneity was shown in two solid
      tumors by clinical and the result of a genomic analysis. Of particular interest
      was that cell-free DNA could be a powerful tool to look into these dynamic
      changes.

PMID- 27687628
TI  - [Which patients with infective endocarditis require emergency surgery?]
AB  - Half of patients with infectious endocarditis have surgery during the active
      phase of infective endocarditis (before the end of antibiotic therapy). The
      American Heart Association and the European Society of Cardiology, independently
      from each other, have published guidelines in September 2015. As regards surgical
      indications, these guidelines are similar. The surgical indication must be a
      common decision of a multidisciplinary team of experts in cardiology, cardiac
      surgery, imaging and infectious diseases. The main indications are heart failure,
      non-infectious process control and prevention of embolisms.

PMID- 27687630
TI  - Surveillance liver MRI for monitoring patients with known or suspected chronic
      liver disease.

PMID- 27687629
TI  - Fitness consequences of polymorphic inversions in the zebra finch genome.
AB  - BACKGROUND: Inversion polymorphisms constitute an evolutionary puzzle: they
      should increase embryo mortality in heterokaryotypic individuals but still they
      are widespread in some taxa. Some insect species have evolved mechanisms to
      reduce the cost of embryo mortality but humans have not. In birds, a detailed
      analysis is missing although intraspecific inversion polymorphisms are regarded
      as common. In Australian zebra finches (Taeniopygia guttata), two polymorphic
      inversions are known cytogenetically and we set out to detect these two and
      potentially additional inversions using genomic tools and study their effects on
      embryo mortality and other fitness-related and morphological traits. RESULTS:
      Using whole-genome SNP data, we screened 948 wild zebra finches for polymorphic
      inversions and describe four large (12-63 Mb) intraspecific inversion
      polymorphisms with allele frequencies close to 50 %. Using additional data from
      5229 birds and 9764 eggs from wild and three captive zebra finch populations, we
      show that only the largest inversions increase embryo mortality in
      heterokaryotypic males, with surprisingly small effect sizes. We test for a
      heterozygote advantage on other fitness components but find no evidence for
      heterosis for any of the inversions. Yet, we find strong additive effects on
      several morphological traits. CONCLUSIONS: The mechanism that has carried the
      derived inversion haplotypes to such high allele frequencies remains elusive. It
      appears that selection has effectively minimized the costs associated with
      inversions in zebra finches. The highly skewed distribution of recombination
      events towards the chromosome ends in zebra finches and other estrildid species
      may function to minimize crossovers in the inverted regions.

PMID- 27687631
TI  - Pd(II) adsorption characteristics of glutaraldehyde cross-linked chitosan
      copolymer resin.
AB  - Deliberating upon the role of solution chemistry in influencing the Pd(II)
      adsorption and desorption characteristics using chitosan based resins, this work
      addresses the competence of glutaraldehyde cross-linked chitosan (GCC) co-polymer
      resin for the removal and recovery of Pd(II) from synthetic electroless plating
      solutions. GCC copolymer adsorbent was prepared by grafting of fixed weight ratio
      (1/17) of medium molecular weight chitosan and glutaraldehyde (25% in H2O).
      Within the adsorption parametric range of 2-10pH, 60-300min contact time, 10-50mg
      adsorbent dosage and 50-500mg/L initial Pd(II) concentration, the solution
      chemistry associated to synthetic ELP solution has been evaluated to strongly
      reduce the adsorption capacity of the GCC resin. Batch equilibrium adsorption
      studies inferred upon the fitness of Langmuir isotherm with a monolayer
      adsorption capacity of 166.67mg/g. Adsorption kinetics and thermodynamic
      parametric evaluations affirmed pseudo-second-order kinetics and spontaneous
      exothermic Pd(II) adsorption on the resin. Further, speciation analysis provided
      valuable insights by indicating greater favourability of Pd(NH3)42+ species (at
      pH=8) than PdEDTA-2 (at lower pH) to foster chemisorption with the GCC resin. In
      summary, the observations affirmed that solution chemistry needs to be addressed
      in laboratory investigations to further industrial application and
      competitiveness of alternate resins.

PMID- 27687632
TI  - Implementing an mHealth system for substance use disorders in primary care: a
      mixed methods study of clinicians' initial expectations and first year
      experiences.
AB  - BACKGROUND: Millions of Americans need but don't receive treatment for substance
      use, and evidence suggests that addiction-focused interventions on smart phones
      could support their recovery. There is little research on implementation of
      addiction-related interventions in primary care, particularly in Federally
      Qualified Health Centers (FQHCs) that provide primary care to underserved
      populations. We used mixed methods to examine three FQHCs' implementation of
      Seva, a smart-phone app that offers patients online support/discussion, health
      tracking, and tools for coping with cravings, and offers clinicians information
      about patients' health tracking and relapses. We examined (a) clinicians' initial
      perspectives about implementing Seva, and (b) the first year of implementation at
      Site 1. METHODS: Prior to staggered implementation at three FQHCs (Midwest city
      in WI vs. rural town in MT vs. metropolitan NY), interviews, meetings, and focus
      groups were conducted with 53 clinicians to identify core themes of initial
      expectations about implementation. One year into implementation at Site 1,
      clinicians there were re-interviewed. Their reports were supplemented by
      quantitative data on clinician and patient use of Seva. RESULTS: Clinicians
      anticipated that Seva could help patients and make behavioral health appointments
      more efficient, but they were skeptical that physicians would engage with Seva
      (given high caseloads), and they were uncertain whether patients would use Seva.
      They were concerned about legal obligations for monitoring patients' interactions
      online, including possible "cries for help" or inappropriate interactions. One
      year later at Site 1, behavioral health care providers, rather than physicians,
      had incorporated Seva into patient care, primarily by discussing it during
      appointments. Given workflow/load concerns, only a few key clinicians monitored
      health tracking/relapses and prompted outreach when needed; two researchers
      monitored the discussion board and alerted the clinic as needed. Clinician
      turnover/leave complicated this approach. Contrary to clinicians' initial
      concerns, patients showed sustained, mutually supportive use of Seva, with few
      instances of misuse. CONCLUSIONS: Results suggest the value of (a) focusing
      implementation on behavioral health care providers rather than physicians, (b)
      assigning a few individuals (not necessarily clinicians) to monitor health
      tracking, relapses, and the discussion board, (c) anticipating turnover/leave and
      having designated replacements. Patients showed sustained, positive use of Seva.
      TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01963234 ).

PMID- 27687633
TI  - Valuing setting-based recreation for selected visitors to national forests in the
      southern United States.
AB  - In this study we estimate selected visitors' demand and value for recreational
      trips to settings such as developed vs. undeveloped sites in U.S. national
      forests in the Southern United States using the travel cost method. The setting
      based approach allows for valuation of multi-activity trips to particular
      settings. The results from an adjusted Poisson lognormal estimator corrected for
      truncation and endogenous stratification reveal that economic value per trip
      estimates are higher for wilderness compared to day-use developed settings,
      overnight-use developed settings, and general forest areas. Estimates of these
      economic values are important to resource managers because their management
      decisions and actions typically control recreational settings. For example,
      managers control developed campground capacity in a national forest, but
      typically not the number of campers below the capacity constraint and the number
      and types of activities visitors engage in during a multi-activity trip to a
      developed campground (within limits since some activities such as discharging a
      firearm are not permitted in a developed campground).

PMID- 27687634
TI  - Radiologically inserted gastrostomy: differences of maintenance of balloon- vs.
      loop-retained devices.
AB  - PURPOSE: To compare outcome and associated complications of ballon- vs. loop
      retained devices for radiologically inserted gastrostomy (RIG). METHODS: From
      2007 to 2011 233 patients (age 63.7 +/- 10.6 years) were referred for a RIG
      because of pharyngeal stricture Intervention was performed with four different
      devices: balloon-retained - Freka(r) GastroTube, Fresenius Kabi (n = 121); MIC(r)
      Gastrostomy Feeding Tube, Kimberly-Clark (n = 34); Russell(r) Gastrostomy Tray,
      Cook Medical Inc. (n = 17); and loop-retained - Tilma(r) Gastrostomy Set, Cook
      Medical Inc. (n = 50). Follow-up was performed with regard to RIG-related
      complications, cause of removal and fatalities. Revision-free survival times
      after RIG were evaluated using Kaplan-Meier analysis and group differences by log
      rank tests. For analysis of demographic and methodical variables multivariate Cox
      regression models were used. RESULTS: With a primary technical success rate of
      95.3% (222/233) a total of 92 instances of revisions were necessary in 66
      patients (66/233, 28.3%) during follow-up (mean 182.8 +/- 86.6 days). The most
      common complication was tube dislodgement (14.3%). There were no significant
      differences between the distinct devices (p = 0.098), but analyzing the data in
      subgroups of balloon-compared to loop-retained gastrostomy tubes we observed a
      significantly higher probability of minor complications for the latter (p =
      0.023). CONCLUSION: As it is significantly less prone to minor complications we
      recommend the use of balloon-retained gastrostomy tubes to improve the
      practicability and maintenance of RIG.

PMID- 27687635
TI  - Alternative functions of the complement protein C1q at embryo implantation site.
AB  - Complement component C1q is one of the recognition molecules of the complement
      system which can serve several functions unrelated to complement activation. This
      molecule is produced at foeto-maternal interface by macrophages as wells as by
      decidual endothelial cells and invading trophoblast. Foetal trophoblast cells
      migrating through the decidua in the early stages of pregnancy synthesize and
      express C1q on their surface, which is actively involved in promoting trophoblast
      endovascular and interstitial invasion of the decidua. These functions are
      mediated by two cell surface receptors, gC1qR and alpha4beta1 integrin, which
      promote trophoblast adhesion and migration through the activation of ERK1/2
      MAPKs. C1q-/- mice manifest increased frequency of foetal resorption, reduced
      foetal weight, and smaller litter size when compared to their wild-type
      counterparts, suggesting that defective local production of C1q may be involved
      in pregnancy disorders, such as pre-eclampsia. C1q acts also as a strong
      angiogenic factor and promotes neovascularization. These studies suggest novel
      and unexpected roles of this complement component in physiological and
      pathological pregnancies.

PMID- 27687636
TI  - Exercise facilities for neurologically disabled populations - Perceptions from
      the fitness industry.
AB  - BACKGROUND: People with neurological disabilities (pwND) face many barriers to
      undertaking physical activity. One option for exercise alongside formal
      physiotherapy is local fitness facilities but accessibility is often found
      wanting and gyms are seen as unwelcoming to pwND. OBJECTIVE: The objective of
      this exploratory study was to investigate the perceptions of fitness facility
      managers with respect to exercise for pwND in a gym environment. The aim was to
      identify potential barriers to provision by the fitness industry for pwND.
      METHODS: The participants included those who were in a position to influence
      provision at a policy level and those working at management level within fitness
      providers. A mixed methods approach was used: a quantitative questionnaire and 4
      qualitative interviews. Descriptive and correlational analysis, thematic content
      analysis and concurrent triangulation analysis was undertaken. RESULTS: Specially
      trained staff is perceived to be necessary to make fitness facilities accessible
      for pwND. CONCLUSIONS: Ensuring the provision of specially trained staff to
      support pwND to exercise in gyms may be the main barrier to provision for this
      population. Investigation into the standard training of fitness professionals
      combining the expertise of neurological physiotherapists with that of fitness
      professionals to meet the needs of pwND would be advantageous.

PMID- 27687637
TI  - Hot-melt extrusion as a continuous manufacturing process to form ternary
      cyclodextrin inclusion complexes.
AB  - The aim of this study was to evaluate hot-melt extrusion (HME) as a continuous
      process to form cyclodextrin (CD) inclusion complexes in order to increase the
      solubility and dissolution rate of itraconazole (ITZ), a class II model drug
      molecule of the Biopharmaceutics Classification System. Different CD derivatives
      were tested in a 1:1 (CD:ITZ) molar ratio to obtain CD ternary inclusion
      complexes in the presence of a polymer, namely Soluplus(r) (SOL). The CD used in
      this series of experiments were beta-cyclodextrin (betaCD), hydroxypropyl-beta
      cyclodextrin (HPbetaCD) with degrees of substitution of 0.63 and 0.87, randomly
      methylated beta-cyclodextrin (Rameb(r)), sulfobutylether-beta-cyclodextrin
      (Captisol(r)) and methyl-beta-cyclodextrin (Crysmeb(r)). Rheology testing and
      mini extrusion using a conical twin screw mini extruder were performed to test
      the processability of the different CD mixtures since CD are not thermoplastic.
      This allowed Captisol(r) and Crysmeb(r) to be discarded from the study due to
      their high impact on the viscosity of the SOL/ITZ mixture. The remaining CD were
      processed by HME in an 18mm twin screw extruder. Saturation concentration
      measurements confirmed the enhancement of solubility of ITZ for the four CD
      formulations. Biphasic dissolution tests indicated that all four formulations had
      faster release profiles compared to the SOL/ITZ solid dispersion. Formulations of
      HPbetaCD 0.63 and Rameb(r) even reached 95% of ITZ released in both phases after
      1h. The formulations were characterized using thermal differential scanning
      calorimetry and attenuated total reflectance infra-red analysis. These analyses
      confirmed that the increased release profile was due to the formation of ternary
      inclusion complexes.

PMID- 27687638
TI  - Structure and function of anhydride-modified forms of human insulin: In silico,
      in vitro and in vivo studies.
AB  - Insulin is a therapeutic protein whose amyloid formation is reported in diabetic
      patients. Four anhydride compounds were used in the current study in order to
      experiment their potential reducing effect on insulin propensity to form amyloid
      fibrils. The modified forms (obtained with succinic-, 3,3-dimethylglutaric, 2
      phenylglutaric-, and (2-Dodecen-1-yl) succinic anhydride), were first
      characterized with regard to melting temperature (Tm), changes in secondary
      structure percentage and hydrophobic surface. Fibril formation was then assessed
      by Congo red absorbance kinetics and transmission electron microscopy.
      Functionality was investigated with the use of an insulin tolerance test in NMRI
      mice. Finally, 10ns molecular dynamics simulations were performed during which
      structural changes, potential energy, gyration radius, RMSD, and accessible
      surface area were monitored. In all cases, alpha-helical structure content of the
      modified forms was reduced, but thermal stability and structural compactness of
      modified insulin were increased except in case of the dodecenylated species. All
      modified insulin forms undergo amorphous aggregation instead of amyloid fibrils
      formation, and dodecenylated insulin makes the largest amorphous aggregates. In
      silico results were overall in accordance with in vitro studies. Finally, only
      succinylated insulin was functional, although dimethylglutaric-modified insulin
      started to show some activity after 2h.

PMID- 27687639
TI  - Influence of barium sulfate X-ray imaging contrast material on properties of
      floating drug delivery tablets.
AB  - The objective of the study was to reveal the influence of necessarily added
      barium sulfate (BaSO4) X-ray contrast material on floating drug delivery tablets.
      Based on literature survey, a chosen floating tablet composition was determined
      containing HPMC and carbopol 943P as matrix polymers. One-factor factorial design
      with five levels was created for evaluation of BaSO4 (X1) effects on experimental
      parameters of tablets including: floating lag time, total floating time, swelling
      , erosion-, dissolution-, release kinetics parameters and X-ray detected volume
      changes of tablets. Applied concentrations of BaSO4 were between 0 and 20.0%
      resulting in remarkable alteration of experimental parameters related especially
      to flotation. Drastic deterioration of floating lag time and total floating time
      could be observed above 15.0% BaSO4. Furthermore, BaSO4 showed to increase the
      integrity of tablet matrix by reducing eroding properties. A novel evaluation of
      dissolutions from floating drug delivery systems was introduced, which could
      assess the quantity of drug dissolved from dosage form in floating state. In the
      cases of tablets containing 20.0% BaSO4, only the 40% of total API amount could
      be dissolved in floating state. In vitro fine resolution X-ray CT imagings were
      performed to study the volume change and the voxel distributions as a function of
      HU attenuations by histogram analysis of the images. X-ray detected relative
      volume change results did not show significant difference between samples. After
      24h, all tablets containing BaSO4 could be segmented, which highlighted the fact
      that enough BaSO4 remained in the tablets for their identification.

PMID- 27687640
TI  - Are Sonographically Measured Vascular Haemodynamic Parameters Reproducible Using
      Magnetic Resonance Imaging?
AB  - OBJECTIVE/BACKGROUND: Hemodynamic measurements of blood flow in the common
      femoral vein and artery can be performed readily using duplex sonography. The
      ratio of venous to arterial volume flow in these vessels, the venous arterial
      flow index (VAFI), is increased in patients with varicose veins and/or chronic
      venous disease. The objective was to determine the reproducibility of
      sonographically measured hemodynamic flow parameters using phase contrast
      magnetic resonance imaging (MRI). METHODS: Based on hemodynamic volume flow
      measurements from the common femoral vein and artery the VAFI was calculated in
      seven patients with varicose veins (C2, Ep, As, Pr) and 32 healthy controls using
      standard duplex sonography and MRI. RESULTS: Based on duplex sonography, the
      average VAFI (VAFI_d) was 1.05 +/- 0.17. The same ratio, using MRI (VAFI_mri) was
      1.05 +/- 0.19. There was a significant correlation between the VAFI_d and the
      VAFI_MRI (p = .0021). In patients with venous disease, the average VAFI_d and
      VAFI_mri were 1.36 +/- 0.21 and 1.36 +/- 0.20, respectively. In contrast, in the
      healthy cohort the VAFI_d was 1.00 +/- 0.12 and the VAFI_mri measured 1.01 +/-
      0.15. As expected, there was a significant difference between the VAFI measured
      in those with venous disease when compared with that of healthy controls (p <
      .0001). CONCLUSION: There is a significant correlation between the VAFI measured
      using sonography and MRI. The study confirmed the elevation of VAFI in patients
      with chronic venous disease.

PMID- 27687641
TI  - Antibiotics in late clinical development.
AB  - Most pharmaceutical companies have stopped or have severely limited investments
      to discover and develop new antibiotics to treat the increasing prevalence of
      infections caused by multi-drug resistant bacteria, because the return on
      investment has been mostly negative for antibiotics that received marketing
      approved in the last few decades. In contrast, a few small companies have taken
      on this challenge and are developing new antibiotics. This review describes those
      antibiotics in late-stage clinical development. Most of them belong to existing
      antibiotic classes and a few with a narrow spectrum of activity are novel
      compounds directed against novel targets. The reasons for some of the past
      failures to find new molecules and a path forward to help attract investments to
      fund discovery of new antibiotics are described.

PMID- 27687642
TI  - Search for new compounds from Kitasato microbial library by physicochemical
      screening.
AB  - The Omura research group of the Kitasato Institute has isolated multiple
      microorganisms over a period of five decades. The resulting collection comprises
      a broad spectrum of microbes, including strains producing novel and diverse
      compounds with biological activities. A bioassay-guided fractionation of
      microbial culture broths has been employed to screen the microbial collection for
      compounds with new biological activities. And numerous novel natural products
      have been discovered among the microbial metabolites produced by members of the
      collection. However, dereplication of already known compounds and their potential
      analogs is a vital part of the discovery process of new microbial natural
      products. Recently, it has become easy to acquire the ultraviolet (UV) and mass
      spectrometry (MS) spectra of many single components of microbial culture broths
      in combination with high-performance liquid chromatography. To achieve most
      effective utilization of our microbial library, new compounds from microbial
      culture broths were investigated by employing an approach based on the physico
      chemical properties using spectral analyses such as UV and MS and color reaction,
      collectively designated as physicochemical (PC) screening. As a result of
      physicochemical screening, many new compounds were identified among the secondary
      metabolites of fresh isolated rare actinomycetes and Streptomyces spp. preserved
      for a long time as producer of biological compounds. In this review, we introduce
      the Kitasato microbial library and the new compounds discovered from the library
      by PC screening.

PMID- 27687643
TI  - Reduced metabolic activity of gut microbiota by antibiotics can potentiate the
      antithrombotic effect of aspirin.
AB  - In this study, we investigated the effects of antibiotics on the pharmacological
      effects of aspirin. The antithrombotic activity of aspirin was evaluated after
      antibiotic treatment using tail bleeding assay. The pyrosequencing analysis and
      selective medium culture assay were performed to investigate the alterations in
      gut microbiota. In addition, the in vitro metabolism assay with fecal suspension
      and in vivo pharmacokinetic experiments with antibiotic treatment were conducted.
      Ampicillin treatment significantly prolonged the bleeding time in aspirin-dosed
      rats. Oral administration of ampicillin significantly reduced gut microbial
      aspirin-metabolizing activity by 67.0% in rats. Furthermore, systemic exposure to
      aspirin and its primary metabolite (M1) was significantly increased in ampicillin
      treated rats. The results from the pyrosequencing and selective medium culture
      with rat fecal samples revealed that ampicillin treatment led to the changes of
      the amounts and composition profile of gut microbiota. These findings suggest
      that co-administration of antibiotics can modulate the metabolism and
      pharmacokinetics of aspirin via suppression of metabolic activity of gut
      microbiota, which could potentiate the therapeutic potency of aspirin.

PMID- 27687645
TI  - [Effect of hypoxia on expressions of MDR1 and MRP2 in rats].
AB  - OBJECTIVE: To study the changes in the physiological parameters and gene
      expression of two drug efflux transporters MDR1 and MRP2 in the small intestine,
      liver and kidney of rats exposed to acute hypoxia. METHODS: Eighteen Wistar rats
      were randomly divided into control group, hypoxia for 24 h group and hypoxia for
      72 h group. Blood samples were obtained from the abdominal aorta of the rats
      after the exposure for analyzing the physiological indexes. The mRNA expressions
      of MDR1 and MRP2 were determined using Real-Time PCR, and their protein
      expressions were detected with enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The physiological parameters of the rats in hypoxia group were
      significantly changed compared with those in the control group. The expressions
      of MDR1 and MRP2 mRNA and proteins in the small intestine, liver and kidney were
      significantly increased in rats with hypoxic exposure than in the control rats
      (P<0.05 or 0.01). As the hypoxic exposure prolonged, the two transporters showed
      different patterns of variation in different tissues. CONCLUSION: Acute hypoxia
      affects the physiological parameters and expression levels of MDR1 and MRP2, thus
      causing changes in the metabolism of the substrates of the transporters. These
      changes may play an important role in the pharmacokinetics of drugs at a high
      altitude.

PMID- 27687644
TI  - Hemodynamic effects of sustained postoperative cardiac resynchronization therapy
      in infants after repair of congenital heart disease: Results of a randomized
      clinical trial.
AB  - BACKGROUND: It is unknown whether continuous cardiac resynchronization therapy
      (CRT) can lead to sustained improvement in hemodynamics after surgery for
      congenital heart disease (CHD). OBJECTIVE: We investigated whether CRT improves
      cardiac index (CI) and blood pressure in infants after biventricular repair of
      CHD. METHODS: We randomized infants younger than 4 months after biventricular CHD
      surgery to standard care or standard care plus CRT for 48 hours or until
      extubation if sooner. Change in the primary outcome of CI and blood pressure over
      time was compared between groups. For subgroup analysis, QRS duration was
      considered prolonged if greater than the 98th percentile. RESULTS: Forty-two
      patients were randomized: 21 controls and 21 patients receiving CRT (median
      weight 4 kg). There were no identified adverse events from pacing. The change in
      CI over time was not different between patients receiving CRT and controls, but
      trended toward improvement in patients with wide QRS who received CRT (n = 9) vs
      controls with wide QRS (n = 8) (+1.65 (0.86) L/(min.m2); P = .06). Controls with
      wide QRS experienced the smallest increase in CI (0.33 L/(min.m2)). Blood
      pressure was significantly higher in infants with wide QRS who received CRT than
      in controls (+7.14 (3.08) mm Hg; P = .02). Serum lactate level, catecholamine
      use, ventilation time, and length of intensive care unit stay were similar
      between the 2 groups. CONCLUSION: CRT improved blood pressure and a trend toward
      higher CI in infants after repair of biventricular CHD with prolonged QRS
      duration. These findings warrant further study of CRT to improve postoperative
      recovery in infants with electrical dyssynchrony.

PMID- 27687646
TI  - [18F-FDG PET/CT findings of primary intestinal lymphoma: analysis of 23 cases].
AB  - OBJECTIVE: To investigate the characteristic 18F-FDG PET/CT findings in patients
      with primary intestinal lymphoma (PIL). METHODS: We collected the clinical and
      18F-FDG PET/CT data of 23 patients with PIL who underwent 18F-FDG PET/CT in our
      center between January, 2005 and January, 2016. The location, morphologies and
      metabolic features of the lesions were analyzed in these patients. RESULTS: In
      the 23 PIL patients, diffusive large B cell lymphoma (DLBCL) and enteropathy-
      associated T cell lymphoma (EATL) were the primary histopathological types,
      accounting for 47.8% and 43.4% of the total patients, respectively. The ileum,
      ileocecus and ascending colon were the most commonly compromised locations
      (57.0%). All the 42 intestinal lesions showed 18F-FDG-avid foci with a mean
      SUVmax of 15.2?8.1 (range 3.6-33.7), and no significant difference was found in
      SUVmax between DLBCL and EATL groups (t=1.851, P=0.073). Diffusive regular or
      irregular intestinal wall thickening was the primary CT finding in PIL lesions
      without significant difference between the two groups (chi2=0.426, P=0.514). The
      aneurismal sign was found in 26.2% (11/42) lesions, more commonly seen in the
      patients with DLBCL than in those with EATL (chi2=8.101, P=0.004). PET/CT
      detected abdominal lymph node involvement of lymphoma was detected in 56.5% of
      the patients, and a small quantity of asites was seen in 30.4% of the patients.
      CONCLUSION: PIL presents with characteristic imaging features in 18F-FDG PET/CT.
      18F-FDG PET/CT is a sensitive imaging modality for detecting inter- and extra
      intestinal lesions of PIL and displays characteristic imaging features of the
      disease.

PMID- 27687647
TI  - [Effects of maternal exposure to vehicle exhaust on the reproductive system and
      DNA methylation in male offspring mice].
AB  - OBJECTIVE: To explore the effect of exposure to vehicle exhaust in pregnant mice
      on the reproductive function and DNA methylation in male offspring mice. METHODS:
      Twenty pregnant mice were randomized into control group and vehicle exhaust
      exposure group (n=10) and exposed to routine laboratory condition and to vehicle
      exhaust for 10 consecutive days (8 h per day) in a tunnel with a heavy traffic,
      where the concentrations of TSP, PM10, PM2.5, SO2 and NOX and the decibel of
      noise were measured. The offspring mice were raised till reaching maturity, and
      the epididymides of the male mice were collected to test the weight coefficients,
      DNA methylation level, and mRNA levels of Aldh7a1 and Rpe. RESULTS: The body
      weight and the weight coefficients of the epididymides and testes differed
      significantly between the exposure group and the control group (P>0.05). The
      concentrations of TSP, PM2.5, PM10 and NOx and the decibel of noise were
      significantly higher in the traffic environment and the control environment
      (P<0.05). Reduced representation bisulphite sequencing (RRBS) and Gene ontology
      (GO) showed that 58 genes had significantly different methylation levels between
      the two groups, mostly relating to the process of spermatogenesis (P<0.05).
      Compared with the control group, Aldh7a1 and Rpe mRNA expressions in the testes
      were down-regulated significantly in the exposure group (P<0.05). CONCLUSION:
      Exposure of pregnant mice to vehicle exhaust causes damages of the reproductive
      function in the male offspring mice.

PMID- 27687648
TI  - [Efficacy of Yunnan Baiyao as an adjuvant treatment for active ulcerative
      colitis: an open-label randomized controlled study].
AB  - OBJECTIVE: To investigate the efficacy of Yunnan Baiyao (YNBY)as an adjuvant
      treatment of active ulcerative colitis. METHODS: A total of 221 patients with
      active ulcerative colitis were randomized into YNBY group (78 cases) and control
      group (143 cases). The patients were followed up for 26 weeks and time of
      remission and serological data (WBC, HGB, PLT, and CRP) were recorded. RESULTS:
      The patients receiving YNBY as an adjuvant therapy had a median remission time of
      9 weeks (95% CI: 8.293-9.707), significantly shorter than that of 13 weeks (95%
      CI: 11.855-14.145) in the control patients (P<0.001). According to the extent of
      the lesion, both YNBY group and control group were classified into E1, E2 and E3
      subgroups, and the median remission time was 7 versus 11 weeks in E1 subgroups
      (P=0.09), 10 versus 13 weeks in E2 subgroups (P=0.04), and 9 versus 14 weeks in
      E3 subgroups (P<0.001). According to the disease severity, the patients in YNBY
      group and control group had a median remission time of 9 versus 10 weeks in mild
      cases (P=0.568), 9 versus 14 weeks in moderate cases (P<0.001), and 11 versus 20
      weeks in severe cases (P=0.001). According to the standard treatment received,
      the median remission time in YNBY group and control group was 9 versus 12 weeks
      in those receiving mesalazine (P<0.001), 9 versus 13 weeks in those receiving
      corticosteroid (P=0.001), and 7 versus 14 weeks in those receiving infliximab
      (P=0.04). Cox proportional hazards regression analysis showed that YNBY was a
      protective factor for disease remission. The remission time was shortened by
      2.283 times (95% CI: 1.69-3.070, P<0.001) in patients having YNBY as an adjuvant
      treatment compared to the control group. CONCLUSION: Patients with active
      ulcerative colitis can benefit from YNBY as an adjuvant treatment, which shortens
      the time of disease remission, relieves the symptoms and improves the quality of
      life of the patients.

PMID- 27687649
TI  - [Effect of chronic arsenic exposure on mouse brain tissue and serum
      metabolomics].
AB  - OBJECTIVE: To observe the effect of chronic arsenic exposure on cerebral cortex
      and serum metabolics of mice and explore the mechanism of arsenic neurotoxicity.
      METHODS: Twelve 3-week-old male C57BL/6J mice were randomly assigned into
      exposure group and control group and exposed to sodium arsenite (50 mg/L) via
      drinking water and deionized water for 12 weeks, respectively. After the
      exposure, arsenic level in the cerebrum was determined by hydride generation
      atomic fluorescence spectrometry. The metabolites in the cerebral cortex and
      serum were determined using gas chromatography-mass spectrometry (GC/MS)
      analysis. Principal component analysis (PCA) was used to analyze the difference
      of the metabolites between the exposure and the control groups. Online tools for
      analyzing metabolic pathways were used to identify the related metabolites
      pathways. RESULTS: Arsenic content in the brain of exposure group was
      significantly higher than that in the control group (P<0.05). The mice exposed to
      arsenic had a higher level of citric acid, phenylalanine, tyrosine, histidine and
      lysine in the cerebral cortex (P<0.05). Serum levels of serine, glycine, proline,
      aspartate and glutamate were significantly higher while alpha-ketoglutaric acid
      level was significantly lower in the exposure group than in the control group
      (P<0.05). PCA analysis showed a significant difference in cerebral cortex and
      serum metabolites between the two groups. CONCLUSION: Chronic arsenic exposure
      may affect the function of the central nervous system by interfering with amino
      acid metabolism and tricarboxylic acid cycle, which may be one of the mechanisms
      of arsenic neurotoxicity.

PMID- 27687650
TI  - [Effects of bisoprolol pretreatment on hypoxia/reoxygenation-induced injury in
      H9c2 cardiomyocytes].
AB  - OBJECTIVE: To investigated the effects of bisoprolol pretreatment on
      hypoxia/reoxygenation (H/R)-induced injury in H9c2 cardiomyocytes. METHODS:
      Cultured H9c2 cells were exposed to hypoxia for 6 h followed by reoxygenation for
      2 h with or without pretreatments with bisoprolol or bisoprolol + LY294002. The
      cell survival was measured by MTT assay, and the cell apoptosis and levels of
      radical oxygen species (ROS) were evaluated with flow cytometry. The protein
      levels of phosphyorylated AKT and phosphorylated GSK3beta in the cells were
      determined by Western blotting. RESULTS: Compared with the normal control cells,
      the cells exposed to H/R injury showed significantly decreased cell survival and
      increased cell apoptosis and ROS production; pretreatment of the cells with
      bisoprolol significantly decreased the cell apoptotic rates and ROS production
      and obviously enhanced the cell survival and protein levels of p-AKT and p
      GSK3beta in the exposed cells. The protective effect of bsioprolol against H/R
      induced cell injury was significantly attenuated by LY294002. CONCLUSION:
      Bisoprolol can protect H9c2 cells against H/R-induced injury and oxidative stress
      by activating PI3K/AKT/Gsk-3beta pathway to increase the phosphorylation of AKT
      and GSK3beta and reduce ROS production.

PMID- 27687651
TI  - [Correlation of DNase I in serum and synovial fluid with inflammatory activity in
      patients with rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the potential role of deoxyribonuclease I (DNase I) in
      the pathogenesis of rheumatoid arthritis (RA). METHODS: DNase I activity was
      measured by radial enzyme-diffusion method in serum samples from 83 RA patients
      and 60 healthy volunteers and in the synovial fluid (SF) from 27 RA patients and
      38 patients with other inflammatory arthritis. SF cfDNA level was measured with
      Pico Green Kit, and the correlation among DNase I activity, cfDNA level and
      clinical parameters of RA patients was analyzed. RESULTS: Serum DNase I activity
      was significantly lower in RA patients than in the healthy control subjects
      (0.3065?0.1436 vs 0.4289?0.1976 U/mL, P<0.001), and was negatively correlated
      with ESR (r=-0.2862, P=0.0122), CRP (r=-0.2790, P=0.0184) and neutrophil cell
      counts (r=-0.287, P=0.011). SF DNase I activity was almost negative in patients
      with RA, ankylosing spondylitis (AS) and gouty arthritis (GA). SF cfDNA level in
      RA patients was significantly higher than that in patients with osteoarthritis
      (100.81?142.98 vs 18.98?31.40 ug/mL, P=0.002), but similar to that in patients
      with AS (45.85?47.67 ug/mL, P=0.428) and GA (162.95?97.49 ug/mL, P=0.132). In
      patients with inflammatory arthritis, SF cfDNA level was positively correlated
      with ESR (r=0.4106, P=0.0116) and CRP (r=0.5747, P=0.0002). CONCLUSION:
      Impairment of DNase I activity may be responsible for the enhanced NETs
      generation and plays a role in the pathogenesis of RA.

PMID- 27687652
TI  - [P38 MAPK signaling pathway mediates advanced oxidation protein product-induced
      epithelial-to-mesenchymal transition in tubular cells].
AB  - OBJECTIVE: To investigate whether the p38 mitogen-activated protein kinase (MAPK)
      signaling pathway mediates advanced oxidation protein products (AOPPs)-induced
      epithelial-to-mesenchymal transition (EMT) in tubular cells. METHODS: Human
      proximal tubular cells (HK-2 cells) exposed to AOPP-bovine serum albumin (BSA)
      were examined for expressions of p38 MAPK and phosphorylated p38 MAPK using
      Western blotting. Western blotting and quantitative RT-PCR were used to examine
      the protein and mRNA expressions of EMT markers E-cadherin and vimentin and
      endoplasmic reticulum stress marker glucose-regulated protein (GRP) 78 in cells
      treated with SB203580 (an inhibitor of the p38 MAPK signaling pathway) prior to
      AOPP exposure. The cells treated with AOPPs following pretreatment with
      salubrinal (an inhibitor of endoplasmic reticulum stress) were also examined for
      expressions of p38 MAPK and phosphorylated p38 MAPK. RESULTS: AOPP treatment
      induced the phosphorylation of p38 MAPK in HK-2 cells. AOPP-induced decrease in E
      cadherin expression and overexpression of vimentin and GRP78 were partly
      inhibited by pretreatment of the cells with SB203580. Salubrina partly suppressed
      AOPP-induced phosphorylation of p38 MAPK in the cells. CONCLUSION: p38 MAPK
      signaling pathway, which is regulated by endoplasmic reticulum stress, might
      mediate AOPP-induced EMT in HK-2 cells.

PMID- 27687653
TI  - [Correlation of CD4+CD29+ regulatory T cells with recurrence and survival time in
      patients with non-small cell lung cancer].
AB  - OBJECTIVE: To investigate the correlation of CD4+CD29+ regulatory T cells (Treg)
      with tumor recurrence and survival time in patients with non-small cell lung
      cancer (NSCLC). METHODS: Fifty-nine patients with NSCLC treated with radical
      surgery were followed up for 5 years. Blood Treg cells were examined during the
      follow-up using flow cytometry (FCM). The sensitivity and specificity of Treg
      cells to predict recurrence of NSCLC were analyzed using receiver-operating
      characteristic (ROC) curve and compared with those of carcinoembryonic antigen
      (CEA) and cytokeratin21-1 (Cyfra21-1). The influences of gender, age, occupation
      and radiotherapy on survival time of the patients were analyzed with Kaplan-Meier
      method. RESULTS: Among the 59 patients, the shortest survival time was 23 months
      while the longest time was over 67 months. Nineteen patients had NSCLC
      recurrence, and 17 (28.81%) of them died of metastasis during the follow-up. The
      frequencies of blood Treg cells in patients who did not receive radiotherapy and
      in patients with tumor recurrence were significantly higher than those in
      patients receiving radiotherapy and in patients free of recurrence (P=0.000). ROC
      curves showed that the area under curve (AUC) lowered in the order of Treg cells,
      Cyfra21-1, CEA (P=0.002, 0.006 and 0.013, respectively) with 95% confidence
      interval (CI) of 0.649-0.981, 0.621-0.936 and 0.584-0.944, respectively. At the
      cut-off value of 7.53%, the sensitivity and specificity of Treg cells to predict
      NSCLC recurrence was 91.42% and 87.59%, respectively. The five-year survival rate
      of the 59 patients was 71.18% (42/59), and Kaplan-Meier analysis revealed a
      longer survival time in female patients (P=0.038), in patients below 50 years of
      age (P=0.013), in patients not engaging in mental work (P=0.029), and in patients
      receiving radiotherapy (P=0.003). CONCLUSION: Treg cells has a better efficiency
      than Cyfra21-1 and CEA to predict tumor recurrence in patients with NSCLC
      following radical surgery. The male gender, an age beyond 50 years, an occupation
      of mental work, and failure to receive radiotherapy are all risk factors for
      recurrence of NSCLC.

PMID- 27687654
TI  - [Association of waist-to-hip ratio with chronic kidney disease in non-diabetic
      subjects].
AB  - OBJECTIVE: To explore the relationship between waist-to-hip ratio (WHR) and
      chronic kidney disease (CKD) in non-diabetic subjects and compare the difference
      between male and female subjects. METHODS: We performed a cross-sectional survey
      among 2142 community-based southern Chinese participants without diabetes from
      June to October 2012. We divided all the participants into 4 groups according to
      the gender-specific quartiles of WHR. Logistic regression models were used to
      explore the associations of WHR with CKD in these subjects. RESULTS: In the
      unadjusted model, WHR was significantly associated with CKD in women (OR=7.29,
      95% CI: 3.56-16.32, P<0.001), and the association was still significant (OR=6.13,
      95% CI: 2.56-15.20, P=0.003 ) after adjustment for the potential confounders
      (including age, history of hypertension, coronary heart disease, current smoker,
      physical inactivity, education level, systolic blood pressure, diastolic blood
      pressure, serum triglyceride, serum high density lipoprotein, blood glucose, and
      BMI). The odds ratio (OR) for having CKD in the highest versus lowest quartile of
      WHR levels was 2.44 (95% CI: 0.98-4.97, P=0.103) in men in the unadjusted model.
      CONCLUSION: WHR levels are associated with CKD in non-diabetic women but not in
      non-diabetic male subjects.

PMID- 27687655
TI  - [Role of specificity protein 1 in modulating radiosensitivity of cervical cancer
      cell lines].
AB  - OBJECTIVE: To investigate the role of specificity protein 1 (Sp1) in regulating
      radiosensitivity of cervical cancer cell lines. METHODS: We analyzed Sp1
      expression in 6 different cervical cancer cell lines (SiHa, HeLa, Caski, Me180,
      Ms751, and C33a) using Western blotting and real-time PCR. Clonogenic survival
      assay and curve fitting were used to assess the changes in radiosensitivity of
      Me180 cells transfected with lentivirus-mediated shRNA vector targeting sp1 and
      HeLa cells transfected with sp1 over-expression vector. RESULTS: In the 6 cell
      lines tested, the cellular expression levels of Sp1 decreased gradually in the
      order of Me180, Caski, C33a, SiHa, Ms751, and HeLa. SP1 knockdown with lentivirus
      mediated shRNA significantly lowered the survival rate of Me180 cells following
      radiation exposure (P<0.05), and obviously lowered the values of SF2, D0 and Dq
      but significantly increased alpha/beta of the cells. Compared with the cells
      transfected with the mock vector, HeLa cells with sp1 over-expression showed a
      significantly increased survival following radiation exposure (P<0.05) with
      obviously increased values of SF2, D0 and Dq but significantly lowered
      alpha/beta. CONCLUSION: Silencing Sp1 can increase the radiosensitivity while Sp1
      overexpression enhances the radioresistance of cervical cancer cell lines,
      suggesting an important role of Sp1 in radiotherapy for cervical cancer.

PMID- 27687656
TI  - [Correlation of serum omentin-1 and chemerin with gestational diabetes mellitus].
AB  - OBJECTIVE: To investigate the relationship of serum omentin-1 and chemerin with
      gestational diabetes mellitus (GDM). METHODS: Serum levels of omentin-1 chemerin,
      glycolipids biochemical index, inflammation index, fasting insulin (FINS), and
      insulin resistance indexes (HOMA-IR) were determined in 85 women with GDM and 85
      pregnant women with normal glucose tolerance (NGT). RESULTS: BMI, FPG, hs-CRP,
      blood lipids, blood glucose, FINS, HOMA-IR and serum chemerin level were all
      significantly higher while serum omentin-1 significantly lower in GDM group than
      in NGT group (P<0.05). In both groups, serum omentin-1 level was significantly
      lower and serum chemerin was significantly higher in obese subjects than in the
      non-obese subjects (P<0.05). Obesity before delivery and/or HOMA-IR >=2 was
      associated with a significantly decreased serum omentin-1 level; serum chemerin
      increased significantly in obese women before delivery but was not associated
      with HOMA-IR. Serum omentin-1 level was positively correlated with HDL but
      inversely with BMI (at pregnancy and before delivery), FPG, FINS and HOMA-IR;
      Chemerin was positively correlated with TC, TG, hs-CRP and FPG; serum omentin-1
      and chemerin levels were not significant correlated (P=0.301). In women with GDM,
      BMI at pregnancy, TG, FPG, and FINS were all independent factors affecting serum
      omentin-1; TG, LDL, and hs-CRP were independent factors affecting serum chemerin.
      CONCLUSION: An decreased serum omentin-1 can be indicative of glucose and lipid
      metabolism disorder and insulin resistance, and an increased serum chemerin level
      indicates hyperlipidemia and chronic inflammation in pregnant women. Both of the
      adipokines are closed associated with GDM and probably participate in the
      occurrence and development of GDM.

PMID- 27687657
TI  - [Distribution of podophyllotoxin-loaded nanostructured lipid carriers after
      topical application on cervical mucosa in Tibet minipigs].
AB  - OBJECTIVE: To assess the distribution and systemic toxicity of podophyllotoxin
      loaded nanostructured lipid carriers (POD-NLC) after topical application on the
      cervical mucosa in Tibet minipigs. METHODS: Twelve Tibet mini-pigs were
      randomized into test group and control group to receive topical application of
      0.5% POD-NLC and 0.5% POD tincture, respectively, on the cervical mucosa.
      Cervical mucosal irritation, targeted distribution and systemic absorption of POD
      were observed at different time points within 24 h after the drug application.
      RESULTS: No local inflammation reaction was observed in the test group, while
      serious local irritations (swelling, blisters, blood blisters, erosion and
      ulceration) occurred in the control group. The fluorescence intensity of POD in
      the mucosal tissue reached the peak level at 4 h after drug application in the
      control group, while the POD fluorescence intensity increased slowly and reached
      the peak level at 16 h in the test group. The peak blood POD concentration
      occurred at 6 h after POD-NLC application in the test group (14.28?0.33 ng/mL),
      as compared to 4 h in the control group (42.46?0.32 ng/mL). At all the time
      points within 24 h, blood POD concentration remained significantly lower in the
      test group than in the control group (P<0.05), and the area under curve of blood
      POD concentration in the control group was 1.38-fold greater than that in the
      test group. CONCLUSION: POD-NLC allows sustained release of POD and achieves a
      higher POD concentration in the mucosal tissue without causing local irritation
      or obvious systemic toxicity in Tibet minipigs.

PMID- 27687658
TI  - [Construction of a lentivirus vector expressing wheat germ agglutinin and its
      infection in human adipose-derived stem cells].
AB  - OBJECTIVE: To construct a lentivirus vector carrying wheat germ agglutinin (WGA)
      and evaluate its ability of tracing WGA in the brain of mice with ischemic brain
      injury. METHODS: WGA gene was inserted into the lentiviral vector Plvx IRES
      ZsGreen1 using genetic engineering methods. 293T cells were transfected with the
      vector and 3 packaging plasmids (RPEV, PRRE, and VSVG) to obtain the recombinant
      lentivirus for infection of human adipose-derived stem cells (hADSCs). The
      infected hADSCs were injected into the damaged brain area by in situ injection in
      a mouse model of middle cerebral artery occlusion (MCAO) and the expression of
      GFP was traced. RESULTS: Immunofluorescence identification detected WGA protein
      expression in the infected hADSCs, which survived in the infarct area of mice
      with MCAO. CONCLUSION: Packaging WGA gene in lentivirus is a reliable approach to
      allow efficient neuroanatomical tracing of various cells.

PMID- 27687659
TI  - [Comparison of endothelial differentiation capacity of adipose-derived stem cells
      and bone marrow mesenchymal stem cells from rats].
AB  - OBJECTIVE: To compared the differentiation capacity of rat adipose-derived stem
      cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) into endothelial
      cells. METHODS: Rat BMSCs and ASCs were isolated, cultured and identified for
      cell surface markers using flow cytometry. The cell growth curves were drawn by
      CCK-8 assay, and the cells in active growth were induced for endothelial
      differentiation following standard protocols. On day 21 of induction, the cells
      were examined for mRNA expressions of endothelial cell specific markers CD31,
      KDR, and vWF using qPCR. Immunostaining was performed to observe the expression
      of CD31 on the cells. The induced cells were also tested for Dil-labeled
      acetylated low-density lipoprotein (ac-LDL) uptake ability. The tube-forming
      ability of the induced cells was verified on Matrigel. RESULTS: We successfully
      isolated rat ASCs and BMSCs. Morphologically, ASCs were similar with BMSCs, both
      having long spindle-shaped and fibroblast-like morphology. Flow cytometry showed
      that both BMSCs and ASCs had high expressions of mesenchymal markers CD29 and
      CD90 and a low expression of hematopoietic cell surface markers CD45. CCK-8 assay
      showed that ASCs proliferated more quickly than BMSCs. The cells with induced
      endothelial differentiation exhibited increased levels of CD31, KDR, and vWF mRNA
      expressions and immunofluorescent staining identified CD31 antigen expression on
      the cell membrane. Fluorescence microscopy revealed red fluorescence in the
      induced cells suggesting uptake of Dil-Ac-LDL by the cells. The induced cells
      were capable of forming tube on Matrigel, confirming their identity of
      endothelial cells. CONCLUSION: Both rat BMSCs and ASCs can be induced to
      differentiate into endothelial cells, but ASCs differentiate more quickly into
      endothelial cells and possess a stronger proliferation ability, suggesting its
      greater potential than BMSCs in future applications.

PMID- 27687660
TI  - [Propofol suppresses migration and invasion of breast cancer MDA-MB-231 cells by
      down-regulating H19].
AB  - OBJECTIVE: To explore the effect of propofol on H19 expression, migration and
      invasion of human breast cancer MDA-MB-231 cells in vitro. METHODS: MDA-MB-231
      cells were randomly divided into 5 groups for treatment with basal medium, DMSO,
      or propofol at concentrations of 25, 50, and 100 umol/L. H19 expression of the
      treated cells was assessed with RT-PCR, and the changes of cell motility,
      migration and invasion were evaluated with wound-healing assay and Transwell
      assays. RESULTS: Treatment of the cells with 25, 50, and 100 umol/L propofol for
      24 h down-regulated H19 by 17.83%, 37.50% and 63.67% (P<0.05), and suppressed
      cell motility by 13.46%, 36.54% and 46.17% (P<0.05), cell migration by 27.93%,
      57.90% and 76.51% (P<0.05), and cell invasion by 25.72%, 53.32% and 81.43%
      (P<0.05), respectively. CONCLUSION: Propofol-induced cell migration and invasion
      suppression are partially mediated by down-regulating H19 in MDA-MB-231 cells in
      vitro.

PMID- 27687661
TI  - [Super-resolution reconstruction for 4-dimensional computed tomography of the
      lung using graph cuts].
AB  - Four-dimensional computer tomography (4D-CT) has a great value in lung cancer
      radiotherapy for its capability in providing lung information with respiratory
      motion. We employed a global graph cuts super-resolution (SR) reconstruction
      method to reconstruct high-resolution lung 4D-CT images. First, the high
      resolution images reconstruction energy function was built based on a Maximum a
      posteriori Markov Random Field (MAP-MRF) formulation. The energy function was
      then transformed to a graph formulation, which was solved using graph cut
      algorithm. All the evaluation results showed that this approach outperformed the
      line interpolation and projection onto convex sets (POCS) approach with an
      improved structural clarity.

PMID- 27687662
TI  - [TRPM8 mediates PC-12 neuronal cell apoptosis induced by oxygen-glucose
      deprivation through cAMP-PKA/UCP4 signaling].
AB  - OBJECTIVE: To explore the molecular mechanism responsible for apoptosis of PC-12
      neuronal cells induced by oxygen-glucose deprivation (OGD). METHODS: PC12 cells
      were exposed to OGD for 24 h to simulate ischemia-reperfusion injury. Flow
      cytometry was employed detect the cell apoptosis, and the expresions of TRPM8,
      UCP4, cAMP and PKA in the exposed cells were detected with RT-PCR and Western
      blotting. The changes in the expressions of Bax, Bcl-2, cAMP, PKA and UCP4
      proteins were detected in the exposed cells in resposne to inhibition of TRPM8
      and cAMP-PKA signal or over-expression of UCP4. RESULTS: OGD for 24 induced
      obvious apoptosis in PC-12 cells and caused TRPM8 over-expression and inhibition
      of UCP4 and cAMP-PKA signaling. Inhibiting TRPM8 expression reduced the cell
      apoptosis and up-regulated cAMP, p-PKA and UCP4 in the cells exposed to OGD. In
      cells exposed to OGD, inhibition of TRPM8 and cAMP-PKA signaling suppressed the
      expressio of UCP4 and increased the cell apoptosis. CONCLUSION: TRPM8 mediates
      OGD-induced PC12 cell apoptosis through cAMP-PKA/UCP4 signaling.

PMID- 27687663
TI  - [Expression of CDK6 in early ovarian cancer and its clinical significance].
AB  - OBJECTIVE: To explore the expression of CDK6 in early ovarian cancer and explore
      its clinical significance. METHODS: Real-time PCR and immunohistochemistry was
      used to examine the differential expression of CDK6 mRNA and protein in ovarian
      cancer and normal ovarian tissues. The correlation of CDK6 expression with the
      clinical characteristics and prognosis of the patients was analyzed. RESULTS: The
      expression of CDK6 mRNA was obviously up-regulated in 36 ovarian cancer tissues
      as compared to that in 16 ovarian tissues. Immunohistochemistry demonstrated that
      CDK6 protein was expressed in both the cytoplasm and cell nuclei. Compared with
      the 48 normal ovarian tissues, the 121 ovarian cancer tissues showed
      significantly up-regulated CDK6 protein expression (P=0.044). Increased CDK6
      protein expression was not significantly correlated with the clinical features of
      the patients with ovarian cancer, but showed a significant negative correlation
      with the patients' prognosis (P=0.006). Multivariate analysis suggested that CDK6
      expression level was an independent prognostic indicator (P=0.008) for the
      survival of patients with ovarian cancer. CONCLUSION: Increased CDK6 protein
      expression may promote the development and progression of early ovarian cancer.

PMID- 27687664
TI  - [Relationship between vitamin D receptor gene polymorphism and preterm birth].
AB  - OBJECTIVE: To explore the relationship between vitamin D receptor (VDR) gene pol
      ymorphisms at Fok I site and the risk of preterm birth for potential intervention
      of of preterm birth or threatened premature delivery. METHODS: Fifty-seven women
      with preterm birth and 84 with full-term birth were included in this analysis.
      Polymerase chain reaction-restriction frag-ment length polymorphism (PCR-RFLP)
      was performed to identify VDR gene Fok I geno-types. RESULTS: No significant
      difference was found in age, D-dimer (DDI), fibrinogen (Fg), serum calcium
      (Ca2+), leukocyte count or glycosylated hemoglobin (HbA1c) level between the
      women in the preterm and full-term birth groups (P>0.05). The two groups differed
      signifi-cantly in the distribution of VDR gene Fok I site genotypes and allele
      frequency of F/F (P<0.05).The frequency of FF genotype was significantly higher
      in the preterm group than in the full-term group. Compared with Ff and ff
      genotypes, FF genotype was associated with an in-creased risk of preterm delivery
      (chi2=9.701, P=9.701, OR=3.320, 95% CI [1.560, 7.066]). In the preterm group, the
      maternal age, DDI, Fg, serum Ca2+, leukocyte count or HbA1c did not differ
      significantly between the genotypes (P>0.05). CONCLUSION: VDR gene Fok I site
      geno-types are related with preterm birth, and the FF genotype may serve as a
      potential risk factor for preterm birth.

PMID- 27687665
TI  - [Prognostic value of preoperative carcinoembryonic antigen level in patients with
      stage I-III colorectal cancer].
AB  - OBJECTIVE: To evaluate the prognostic value of preoperative serum
      carcinoembryonic antigen (CEA) level in patients with stage I-III colorectal
      cancer. METHODS: The clinicopathological data and prognosis were retrospectively
      analyzed for 393 patients with colorectal cancer treated in our hospital from
      January, 2003 to December, 2013. Of these patients, 136 had elevated serum CEA
      level (>=5 ng/mL) and 257 did not show serum CEA elevation (<5 ng/mL). RESULTS:
      The two groups of patients showed significant differences in the tumor size,
      degree of tumor differentiation and lymph node metastasis (P<0.05). Cox
      proportional hazards model suggested that an elevated preoperative CEA level was
      a risk factor for survival and tumor recurrence, and increased the risks of death
      and tumor recurrence by 1.59 and 1.89 folds, respectively. Compared with the
      patients without CEA elevation, those with elevated CEA level had a significantly
      higher mortality rate (28.7% vs 19.8%, P<0.05) and tumor recurrence rate (32.4%
      vs 19.1%, P<0.05) with a significantly lower cumulative total survival rate and
      cumulative disease-free survival rate (P<0.05); the same results were also found
      in stage-III patients (P<0.05). CONCLUSIONS: New survival and recurrence data can
      be generated by incorporating serum CEA level in TNM staging system for more
      accurate prognostic assessment of the patients.

PMID- 27687666
TI  - [Propofol suppresses invasion of human lung cancer A549 cells by down-regulating
      aquaporin-3 and matrix metalloproteinase-9].
AB  - OBJECTIVE: To investigate the effect of propofol on cell invasion and expressions
      of aquaporin-3 (APQ-3) and matrix metalloproteinase-9 (MMP-9) in human lung
      adenocarcinoma cancer A549 cells. METHOD: A549 cells were treated with propofol
      at the concentrations of 25, 50, and 100 umol/L for 12 or 24 h. RT-PCR was used
      to detect the effect of propofol on AQP-3 mRNA level in A549 cells, and the
      effects of propofol treatments for 24 h on AQP-3 and MMP-9 protein expression and
      the invasive ability of A549 cells were assessed with Western blotting and
      Transwell assay, respectively. RESULTS: Compared with the control cells, the
      cells treated with 25, 50, and 100 umol/L propofol showed a obvious inhibition of
      AQP-3 mRNA expression, with inhibition rates ranging from 0.19 to 0.65 in cells
      with a 12-h treatment and from 0.13 to 0.41 in cells treated for 24 h; 100 umol/L
      propofol treatment for 24 h produced the strongest inhibitory effect (0.13?0.035,
      P<0.05). AQP-3 protein expression in cells treated with 25, 50, and 100 umol/L
      propofol for 24 h (0.91?0.009, 0.60?0.020, and 0.57?0.006, respectively) and MMP
      9 protein expression in cells treated with 50 and 100 umol/L propofol for 24 h
      (0.65?0.006 and 0.46?0.021, respectively) were significantly lower than those in
      the control cells (P<0.05). Treatment with 25, 50, and 100 umol/L propofol for 24
      significantly lowered the number of invading cells (122.55?17.20, 96.33?5.82, and
      74.33?2.85, respectively) compared with the control group (199.33?23.88, P<0.05).
      CONCLUSION: Treatment with 50 and 100 umol/L propofol inhibits cell invasion by
      down-regulating the expression of AQP-3 and MMP-9 in A549 cells.

PMID- 27687667
TI  - [Rituximab combined with EPOCH regimen for treatment of diffuse large B cell
      lymphoma of the gastrointestinal tract: analysis of 4 cases].
AB  - We treated 4 with a diagnosis of diffuse large B cell lymphoma involving the
      gastrointestinal tract with rituximab combined with adjusted dose EPOCH (R-DA
      EPOCH) scheme based on a comprehensive analysis of the onset process, clinical
      and pathological features, and prognosis of the patients, and evaluated their
      treatment response. Complete remission (CR) was achieved in 3 patients after the
      treatment and 1 patient with diabetes and hypertension died due to severe
      infection. R-DA-EPOCH regimen as the first-line treatment of gastrointestinal
      diffuse large B cell lymphoma has a good short-term efficacy, but its long-term
      efficacy awaits further evaluation in future studies with larger sample sizes.

PMID- 27687668
TI  - [Hemoglobin H disease with a rare alpha-thalassemia gene mutation (-
      SEA/alpha*92A>Galpha): pedigree analysis and genetic diagnosis].
AB  - OBJECTIVE: To identify a rare alpha-thalassemia gene mutation in a family from
      south China and perform a pedigree analysis and genetic diagnosis of hemoglobin H
      (HbH) disease caused by this mutation. METHODS: Peripheral blood samples were
      collected from the family members for analysis of the hematological phenotype and
      routine test of thalassemia genes. DNA sequencing was carried out for samples
      that showed genotype and phenotype inconsistency. RESULTS: A rare alpha
      thalassemia *92A>G gene mutation was detected within this family. The proband and
      his sister were confirmed to have non-deletional HbH disease with alpha-
      SEA/alpha*92A>Galpha genotype. The proband's brother was confirmed to have an
      alpha-thalassemia trait with the genotype of -alpha3.7/alpha*92A>Galpha. The
      proband's father was identified as an alpha-thalassemia silent carrier with the
      genotype of alphaalpha/alpha*92A>Galpha. CONCLUSION: A rare alpha-thalassemia
      *92A>G gene mutation was identified for first time in south China. The
      description of the basic phenotypic characteristics of alpha-thalassemia trait
      and silent carrier caused by this mutation enriches the alpha-thalassemia gene
      mutation spectrum in Chinese population and helps in population screening,
      clinical molecular diagnosis and genetic counseling.

PMID- 27687669
TI  - [Clinicopathological characteristics and prognosis of uterine malignant mixed
      Mullerian tumor].
AB  - OBJECTIVE: To evaluate the clinicopathological characteristics, treatment and
      prognosis of uterine malignant mixed mullerian tumor. METHODS: The clinical,
      pathologic and follow-up data of 16 patients with uterine malignant mixed
      Mullerian tumor treated in our hospital between March, 2003 and June, 2015 were
      analyzed. RESULTS: The 16 patients had a median age of 58 years at diagnosis, and
      13 of them were postmenopausal. The number of patients with FIGO stage Ia, Ib,
      II, IIIa, IIIc2, and IV was 7, 3, 1, 3, 1, and 1, respectively. In 15 patients
      who received uterine segment diagnostic curettage, pathological examination all
      reported malignant results. Among the 15 patients having serum CA125 level test
      upon admission, 2 had elevated CA125 levels. The overall and disease-free
      survival rates of the 16 patients were 75% and 68.8%, respectively, and the 3
      year survival rate of 13 patients who were followed up for at least 3 years was
      72.7%. Two out of 12 patients receiving retroperitoneal lymph?node?dissection?had
      had postoperative recurrence, as compared with 3 out 4 who did not had the
      operation; tumor recurrence was found in 3 out of 13 patients receiving
      postoperative chemotherapy, as compared with 2 out of 3 patients who did not have
      chemotherapy; tumor recurrence occurred in 1 out of 10 patients receiving
      radiotherapy, as compared with 4 out of 6 patients without radiotherapy. The
      recurrence rates in 11 patients with FIGO stage I-II was 18.2%, and that among
      the 5 patients with FIGO stage III-IV was 60.0%. CONCLUSIONS: Uterine segment
      diagnostic curettage has a high diagnostic value for uterine malignant mixed
      Mullerian tumor. FIGO stage is the important prognostic factor for these
      patients, and early?diagnosis, accurate surgical staging, platinum-based
      chemotherapy and postoperative pelvic radiotherapy are all associated with a
      better prognosis.

PMID- 27687670
TI  - [HBsAg seroconversion after entecavir therapy for 7 years following a poor
      response to interferon-alpha 2b monotherapy in a HBeAg-negative patient with
      chronic hepatitis B].
AB  - We report a rare case of HBsAg seroconversion after 7 years of entecavir therapy
      in a 48-year-old HBeAg-negative CHB male patient with chronic hepatitis B (CHB).
      After a poor response to a 48-week interferon-alpha 2b therapy, the patient
      received long-term entecavir therapy. Serum ALT levels became normal and HBV DNA
      viral load was undetectable at the 10th week after commencement of entecavir
      treatment, and seroconversion of HBsAg was detected after 7 years of entecavir
      therapy.

PMID- 27687671
TI  - Identification of small molecules that bind to the mitochondrial protein
      mitoNEET.
AB  - MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc
      finger protein family. Recently mitoNEET has been shown to be a major role player
      in the mitochondrial function associated with metabolic type diseases such as
      obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were
      the first identified ligands to mitoNEET. Since little is known about structural
      requirements for ligand binding to mitoNEET, we screened a small set of compounds
      to gain insight into these requirements. We found that the thiazolidinedione
      (TZD) warhead as seen in rosiglitazone was not an absolutely necessity for
      binding to mitoNEET. These results will aid in the development of novel compounds
      that can be used to treat mitochondrial dysfunction seen in several diseases.

PMID- 27687672
TI  - Design and synthesis of peptide-based macrocyclic cyclophilin inhibitors.
AB  - The efficient assembly of an 18-membered macrocyclic peptide core was realized by
      a straightforward and convergent approach utilizing ring-closing metathesis of
      the corresponding linear tetrapeptides as the key transformation. This approach
      allowed for the facile preparation of a focused library of novel macrocycles that
      culminated in the discovery of a cyclophilin A inhibitor with a Kd=5.4MUM.

PMID- 27687673
TI  - Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC
      development.
AB  - The use of small molecules to regulate cellular levels of specific proteins is
      poised to become a powerful technique in the coming years. Critical to the
      success of any project utilizing such an approach will be the ability to
      synthesize libraries of candidate small molecules for testing in cellular
      systems. Herein, we describe a practical synthesis of a phthalimide-based
      scaffold, which can be easily diversified to make Cereblon-targeting PROTACs. We
      demonstrate the effectiveness of this approach by synthesizing a 'PROTAC toolbox'
      of four amines which can be coupled to inhibitors in a straightforward manner.

PMID- 27687674
TI  - Targeting cytochrome P450 (CYP) 1B1 with steroid derivatives.
AB  - Inhibition of cytochrome P450 1B1 (CYP1B1) represents a promising therapeutic
      strategy, because it would enable action at three different levels: (1) by
      inhibiting the formation of mutagenic 4-hydroxy-estradiol, (2) by inhibiting the
      bioactivation of procarcinogens, and (3) by reducing drug-resistance.
      Surprisingly, few steroids were reported as inhibitors of CYP1B1. From a
      screening performed with 90 steroid derivatives, we identified thioestrone (B19)
      as an inhibitor (IC50=3.4MUM) of CYP1B1. Molecular modeling studies showed that
      the 3-SH group of B19 is closer (3.36A) to the iron atom of the heme system than
      the 3-OH group of enzyme substrates estrone and estradiol (4.26A and 3.58A,
      respectively). B19 also produced a better docking GOLD score that correlated with
      the inhibitory results obtained. The estrane derivative B19 represents an
      interesting lead compound that can be easily modified to extend the structure
      activity relationship study and to provide a next generation of more powerful
      CYP1B1 inhibitors.

PMID- 27687675
TI  - Detection of Infectious Pancreatic Necrosis Virus from the Leeches Hemiclepsis
      marginata and Hirudo medicinalis.
AB  - Leeches have been reported to harbor several important fish pathogens, including
      spring viremia of carp virus, infectious hematopoietic necrosis virus (IHNV), and
      viral hemorrhagic septicemia virus (VHSV), and also may contain blood protozoa.
      In the present study, leeches were collected from water bodies located in
      Kurdistan province, Iran. The specimens were tested for IHNV, VHSV, and
      infectious pancreatic necrosis virus (IPNV) using the PCR method. The results
      showed that two different species of leeches, Hemiclepsis marginata and Hirudo
      medicinalis, were infected by IPNV among the seven species studied. The infected
      leeches were found in areas that were polluted with untreated sewage coming from
      upstream fish farms culturing Rainbow Trout Oncorhynchus mykiss. In addition, the
      fish at fish farms in the vicinity had been infected with IPNV 9 months
      previously. Our results showed that the virus causing infectious pancreatic
      necrosis is present in the leeches H. marginata and H. medicinalis, suggesting
      that leeches are a potential source of IPNV in fish farms. Received October 14,
      2015; accepted June 1, 2016.

PMID- 27687676
TI  - The effect of CPAP treatment on venous lactate and arterial blood gas among
      obstructive sleep apnea syndrome patients.
AB  - PURPOSE: The aim of this observational study was to investigate the influence of
      continuous positive airway pressure (CPAP) on arterial blood gas and venous
      lactate, markers of tissue hypoxia, among obstructive sleep apnea syndrome (OSAS)
      patients, and determine the risk factor of serum lactate and hydrogen ion
      concentration (PH) in OSAS patients. MATERIALS AND METHODS: One-hundred and nine
      patients with newly diagnosed OSAS were enrolled in the study. All individuals
      were treated with CPAP for one night. Venous lactate and arterial blood gas were
      gathered from all subjects in the morning at the end of polysomnography and the
      next morning after CPAP treatment. RESULTS: Of the 109 selected subjects, the
      average lactate level was 2.23 +/- 0.59 mmol/L, and the mean PH, PaO2, and PaCO2
      were 7.380 +/- 0.23, 88.14 +/- 17.83 mmHg, and 38.70 +/- 4.28 mmHg, respectively.
      Compared to baseline, lactic acid significantly decreased (2.10 +/- 0.50 mmol/L,
      p = 0.03), while PH increased (7.388 +/- 0.27, p < 0.05) after CPAP treatment. In
      addition, neck circumference and the polysomnographic parameters, including apnea
      hypopnea index, oxygen desaturation index (ODI), mean oxygen saturation (SpO2),
      and the percentage of sleep time with SpO2 <90 % (TS90 %), positively correlated
      with lactate, while age correlated negatively with lactate (all p < 0.05).
      Significantly positive associations were found between age, neck circumference,
      and PH; furthermore, a negative correlation was found between ODI and PH.
      Finally, after adjusting for confounding factors, TS90 % was the major
      contributing predictor for elevated lactate (p < 0.05), and age was a predictor
      for an increase in PH (p < 0.05). CONCLUSIONS: The results indicated that CPAP
      treatment could reduce serum lactate and increase PH in OSAS patients and might
      alleviate acid-base balance disorders in OSAS. Furthermore, TS90 % was a risk
      factor for elevated lactate, and age was independently associated with PH.

PMID- 27687677
TI  - A new alpha-pyrone from the mangrove endophytic fungus Phomopsis sp. HNY29-2B.
AB  - A new alpha-pyrone derivative, phomopyrone A (1), together with two known
      compounds (2-3), was isolated from the culture of the mangrove endophytic fungus
      Phomopsis sp. HNY29-2B. Their structures were determined by detailed analysis of
      spectroscopic data. The configuration of 1 was further confirmed by X-ray
      diffraction. All isolated compounds were evaluated for antibacterial and
      antioxidative activities. Compound 2 exhibited antibacterial activities with
      minimal inhibition concentration (MIC) values of 25 and 50 MUM against Bacillus
      subtilis and Pseudomonas aeruginosa, and compound 3 showed activities against
      Staphylococcus aureus and B. subtilis with MIC values of 25 and 50 MUM,
      respectively.

PMID- 27687678
TI  - Comparing two lower-dose cisplatin programs for radio-chemotherapy of locally
      advanced head-and-neck cancers.
AB  - Radio-chemotherapy is a common treatment for locally advanced squamous cell head
      and-neck cancers (LA-SCCHN). Cisplatin (100 mg/m2) every 3 weeks is very common
      but associated with considerable toxicity. Therefore, cisplatin programs with
      lower daily doses were introduced. There is a lack of studies comparing lower
      dose programs. In this study, 85 patients receiving radio-chemotherapy with 20
      mg/m2 cisplatin on 5 days every 4 weeks (group A) were retrospectively compared
      to 85 patients receiving radio-chemotherapy with 30-40 mg/m2 cisplatin weekly
      (group B). Groups were matched for nine factors including age, gender,
      performance score, tumor site, T-/N-category, surgery, hemoglobin before radio
      chemotherapy, and radiation technique. One- and 3-year loco-regional control
      rates were 83 and 69 % in group A versus 74 and 63 % in group B (p = 0.12). One-
      and 3-year survival rates were 93 % and 73 % in group A versus 91 and 49 % in
      group B (p = 0.011). On multivariate analysis, survival was significantly better
      for group A (HR 1.17; p = 0.002). In groups A and B, 12 and 28 % of patients,
      respectively, did not receive a cumulative cisplatin dose >=180 mg/m2 (p =
      0.016). Toxicity rates were not significantly different. On subgroup analyses,
      group A patients had better loco-regional control (p = 0.040) and survival (p =
      0.005) than group B patients after definitive radio-chemotherapy. In patients
      receiving adjuvant radio-chemotherapy, outcomes were not significantly different.
      Thus, 20 mg/m2 cisplatin on 5 days every 4 weeks resulted in better loco-regional
      control and survival in patients receiving definitive radio-chemotherapy and may
      be preferable for these patients. Confirmation of these results in a randomized
      trial is warranted.

PMID- 27687679
TI  - Anatomical approach to surgery for intrathoracic goiter.
AB  - The anatomical approach to the intrathoracic goiter (ITG) was used to understand
      its etiology and to rationalize surgical technique of thyroidectomy. For a
      retrospective chart review, we selected cases of multinodular goiter with totally
      ITGs (n = 69; M 29, F 40), while 916 cases with cervical goiter were used for
      comparison. The topography of the thyroid gland was assessed against the tracheal
      rings and against the vertebrae. The regional anatomy of the thoracic inlet was
      assessed by its bony margins and the relations of structures traversing the area.
      Average tracheal-diameter-to-thoracic-inlet ratio was calculated. The ITG group
      consisted of 52 cases of retrosternal goiter (75.4 %), nine cases of
      retrotracheal goiter (13 %), and eight cases of retroesophageal goiter (11.6 %).
      In all but one analyzed cases, the goiters were removed via cervical incision.
      Mean weight of goiters was 183 g. The area of thoracic inlet in the cases of ITG
      had no difference in comparison with the cases of cervical goiter (F/M p =
      0.11/0.15), but the tracheal-diameter-to-thoracic-inlet ratio was significantly
      smaller (F/M p = 0.06/0.04). In the ITG cases, the position of the upper edge of
      the isthmus of the thyroid was about 1.5 tracheal rings lower than in healthy
      individuals (p = 0.03). The area of the thoracic inlet, the neck size, and the
      anteroposterior diameter of the inlet do not affect the development of the ITG.
      The smaller tracheal-diameter-to-thoracic-inlet ratio and the lower position of
      the thyroid gland are the main indicators for the development of the ITG.

PMID- 27687680
TI  - Social support and substitute voice acquisition on psychological adjustment among
      patients after laryngectomy.
AB  - The objective is to clarify whether social support and acquisition of alternative
      voice enhance the psychological adjustment of laryngectomized patients and which
      part of the psychological adjustment structure would be influenced by social
      support. We contacted 1445 patients enrolled in a patient association using mail
      surveys and 679 patients agreed to participate in the study. The survey items
      included age, sex, occupation, post-surgery duration, communication method,
      psychological adjustment (by the Nottingham Adjustment Scale Japanese
      Laryngectomy Version: NAS-J-L), and the formal support (by Hospital Patient
      Satisfaction Questionnaire-25: HPSQ-25). Social support and communication methods
      were added to the three-tier structural model of psychological adjustment shown
      in our previous study, and a covariance structure analysis was conducted.
      Formal/informal supports and acquisition of alternative voice influence only the
      "recognition of oneself as voluntary agent", the first tier of the three-tier
      structure of psychological adjustment. The results suggest that social support
      and acquisition of alternative voice may enhance the recognition of oneself as
      voluntary agent and promote the psychological adjustment.

PMID- 27687681
TI  - Comparison of escalating, constant, and reduction energy output in ESWL for renal
      stones: multi-arm prospective randomized study.
AB  - This study was designed to find out the optimized energy delivery strategy in
      Shock Wave Lithotripsy (SWL) that yield to the best stone-free rate (SFR). In
      this clinical trial, 150 consecutive patients were randomized into three groups:
      (a) Dose escalation, 1500 SW at 18 kV, followed by 1500 SW at 20 kV then 1500 SW
      at 22 kV. (b) Constant dose, 4500 SW at 20 kV. All patients undergo plain X-ray
      film of the urinary tract at day 1, 14, and 90 to assess stone-free rate (SFR)
      which was defined as no stones or painless fragments less than 4 mm. (c) Dose
      reduction, 1500 SW at 22 kV, followed by 1500 SW at 20 kV and then 1500 SW at 18
      kV. The three treatment groups were comparable in terms of age, sex, stone size
      and distribution of the kidneys, and the need for Double J stent use. On day 90,
      the SFR achieved was 82, 90, and 84 % in the escalating, constant, and reduction
      energy groups, respectively. However, this rate was not statistically significant
      (x 2 = 1.38, p level = 0.28). At a slow rate of 60 shocks, there was no
      difference in stone-free rate between different voltages at 1, 14, and 90 days.
      Our randomized clinical trial showed no statistically significant difference in
      SFR between the three groups while using the slow SWL rate. Our trial is the
      first randomized trial comparing the three strategies. As such, a dose adjustment
      strategy while delivering SWL in slow rate was not recommended.

PMID- 27687683
TI  - Corrigendum.

PMID- 27687682
TI  - ADHD Symptoms in Post-Institutionalized Children Are Partially Mediated by
      Altered Frontal EEG Asymmetry.
AB  - Individual differences in the propensity for left versus right frontal
      electroencephalogram (EEG) asymmetry may underlie differences in
      approach/withdrawal tendencies and mental health deficits. Growing evidence
      suggests that early life adversity may shape brain development and contribute to
      the emergence of mental health problems. The present study examined frontal EEG
      asymmetry (FEA) following the transition to family care in children adopted
      internationally from institutional care settings between 15 and 36 months of age
      (N = 82; 46 female, 36 male). Two comparison groups were included: an
      international adoption control consisting of children adopted from foster care
      with little to no institutional deprivation (N = 45; 17 female, 28 male) and a
      post-adoption condition control consisting of children reared in birth families
      of the same education and income as the adoptive families (N = 48; 23 female, 25
      male). Consistent with evidence of greater approach and impulsivity-related
      behavior problems in post-institutionalized (PI) children, PI status was
      associated with greater left FEA than found in the other two groups. In addition,
      left FEA served as a mediator between institutionalization and age 5 ADHD
      symptoms for girls. Age at adoption and other preadoption factors were examined
      with results suggesting that earlier adoption into a supportive family resulted
      in a more typical pattern of brain functioning. Findings support the idea that
      the capacity of brain activity to evidence typical functioning following
      perturbation may differ in relation to the timing of intervention and suggest
      that the earlier the intervention of adoption, the better.

PMID- 27687684
TI  - Novel proteasome inhibitor ixazomib sensitizes neuroblastoma cells to doxorubicin
      treatment.
AB  - Neuroblastoma (NB) is the most common extracranial malignant solid tumor seen in
      children and continues to lead to the death of many pediatric cancer patients.
      The poor outcome in high risk NB is largely attributed to the development of
      chemoresistant tumor cells. Doxorubicin (dox) has been widely employed as a
      potent anti-cancer agent in chemotherapeutic regimens; however, it also leads to
      chemoresistance in many cancer types including NB. Thus, developing novel small
      molecules that can overcome dox-induced chemoresistance is a promising strategy
      in cancer therapy. Here we show that the second generation proteasome inhibitor
      ixazomib (MLN9708) not only inhibits NB cell proliferation and induces apoptosis
      in vitro but also enhances dox-induced cytotoxicity in NB cells. Ixazomib
      inhibits dox-induced NF-kappaB activity and sensitizes NB cells to dox-induced
      apoptosis. More importantly, ixazomib demonstrated potent anti-tumor efficacy in
      vivo by enhancing dox-induced apoptosis in an orthotopic xenograft NB mouse
      model. Collectively, our study illustrates the anti-tumor efficacy of ixazomib in
      NB both alone and in combination with dox, suggesting that combination therapy
      including ixazomib with traditional therapeutic agents such as dox is a viable
      strategy that may achieve better outcomes for NB patients.

PMID- 27687685
TI  - Treatment of epilepsy in patients with Alzheimer's disease.
AB  - INTRODUCTION: Epilepsy is significantly more frequent in AD patients than in age
      matched controls, even though the true extent of the phenomenon is not clear yet.
      Areas covered: In this review, we describe in detail the available data on the
      pharmacological treatment of epilepsy in patients with AD. We also briefly
      describe general principles of AEDs use in elderly, as well as the potential
      cognitive profile of AEDs and safety of concomitant psychotropic drugs in
      patients with epilepsy and AD. Expert commentary: As some preclinical data
      suggest a role of epileptiform discharges in cognitive decline in AD, a prompt
      diagnosis and treatment of seizures in these patients should be pursued. The few
      data on the use of AEDs in AD patients suggest that newer AEDs (in particular
      lamotrigine and levetiracetam) might be good choices. Experimental data even
      support a potential role of some AEDs in modifying the disease course of AD.

PMID- 27687686
TI  - Rhythmic displays of female gibbons offer insight into the origin of dance.
AB  - Dance is a universal art form practiced by all human societies and has many
      functions including sexual attraction, social cohesion, and the therapeutic
      release of energy. Dance also has been reported in a small number of non-human
      primate species, in particular apes. However, its function has not been
      systematically evaluated. We observed 357 intentional, rhythmic, and nonverbal
      dance displays performed by four adult female cao vit gibbons (Nomascus nasutus)
      residing in four polygynous groups during 3000 h of observation in Bangliang,
      Guangxi, China. Females used dance to solicit copulations, as well as to promote
      a social bond with the group's lone adult male. In addition, this display appears
      to represent a form of non-aggressive competition among adult females living in
      the same group. We found that a female who had a weaker social relationship with
      the breeding male increased her social and sexual access to the male by an
      increase in dancing frequency. Given that gibbons dance in various behavioral
      contexts, and appears to serve several important social and sexual functions, a
      greater understanding of this form of gestural communication offers an
      instructive model for examining the origin and evolution of dance in humans and
      other apes.

PMID- 27687688
TI  - Nucleus or cytoplasm? The mysterious case of SIRT1's subcellular localization.

PMID- 27687687
TI  - Bisphosphonates in multicentric osteolysis, nodulosis and arthropathy (MONA)
      spectrum disorder - an alternative therapeutic approach.
AB  - Multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder is a
      rare inherited progressive skeletal disorder caused by mutations in the matrix
      metalloproteinase 2 (MMP2) gene. Treatment options are limited. Herein we present
      successful bisphosphonate therapy in three affected patients. Patients were
      treated with bisphosphonates (either pamidronate or zoledronate) for different
      time periods. The following outcome variables were assessed: skeletal pain, range
      of motion, bone densitometry, internal medical problems as well as neurocognitive
      function. Skeletal pain was dramatically reduced in all patients soon after
      initiation of therapy and bone mineral density increased. Range of motion did not
      significantly improve. One patient is still able to walk with aids at the age of
      14 years. Neurocognitive development was normal in all patients. Bisphosphonate
      therapy was effective especially in controlling skeletal pain in MONA spectrum
      disorder. Early initiation of treatment seems to be particularly important in
      order to achieve the best possible outcome.

PMID- 27687689
TI  - Acoustic omni meta-atom for decoupled access to all octants of a wave parameter
      space.
AB  - The common behaviour of a wave is determined by wave parameters of its medium,
      which are generally associated with the characteristic oscillations of its
      corresponding elementary particles. In the context of metamaterials, the
      decoupled excitation of these fundamental oscillations would provide an ideal
      platform for top-down and reconfigurable access to the entire constitutive
      parameter space; however, this has remained as a conceivable problem that must be
      accomplished, after being pointed out by Pendry. Here by focusing on acoustic
      metamaterials, we achieve the decoupling of density rho, modulus B-1 and
      bianisotropy xi, by separating the paths of particle momentum to conform to the
      characteristic oscillations of each macroscopic wave parameter. Independent
      access to all octants of wave parameter space (rho, B-1, xi)=(+/-,+/-,+/-) is
      thus realized using a single platform that we call an omni meta-atom; as a
      building block that achieves top-down access to the target properties of
      metamaterials.

PMID- 27687690
TI  - SAMSA: a comprehensive metatranscriptome analysis pipeline.
AB  - BACKGROUND: Although metatranscriptomics-the study of diverse microbial
      population activity based on RNA-seq data-is rapidly growing in popularity, there
      are limited options for biologists to analyze this type of data. Current
      approaches for processing metatranscriptomes rely on restricted databases and a
      dedicated computing cluster, or metagenome-based approaches that have not been
      fully evaluated for processing metatranscriptomic datasets. We created a new
      bioinformatics pipeline, designed specifically for metatranscriptome dataset
      analysis, which runs in conjunction with Metagenome-RAST (MG-RAST) servers.
      Designed for use by researchers with relatively little bioinformatics experience,
      SAMSA offers a breakdown of metatranscriptome transcription activity levels by
      organism or transcript function, and is fully open source. We used this new tool
      to evaluate best practices for sequencing stool metatranscriptomes. RESULTS:
      Working with the MG-RAST annotation server, we constructed the Simple Annotation
      of Metatranscriptomes by Sequence Analysis (SAMSA) software package, a complete
      pipeline for the analysis of gut microbiome data. SAMSA can summarize and
      evaluate raw annotation results, identifying abundant species and significant
      functional differences between metatranscriptomes. Using pilot data and simulated
      subsets, we determined experimental requirements for fecal gut
      metatranscriptomes. Sequences need to be either long reads (longer than 100 bp)
      or joined paired-end reads. Each sample needs 40-50 million raw sequences, which
      can be expected to yield the 5-10 million annotated reads necessary for accurate
      abundance measures. We also demonstrated that ribosomal RNA depletion does not
      equally deplete ribosomes from all species within a sample, and remaining rRNA
      sequences should be discarded. Using publicly available metatranscriptome data in
      which rRNA was not depleted, we were able to demonstrate that overall organism
      transcriptional activity can be measured using mRNA counts. We were also able to
      detect significant differences between control and experimental groups in both
      organism transcriptional activity and specific cellular functions. CONCLUSIONS:
      By making this new pipeline publicly available, we have created a powerful new
      tool for metatranscriptomics research, offering a new method for greater insight
      into the activity of diverse microbial communities. We further recommend that
      stool metatranscriptomes be ribodepleted and sequenced in a 100 bp paired end
      format with a minimum of 40 million reads per sample.

PMID- 27687691
TI  - Expression of B4GALNT1, an essential glycosyltransferase for the synthesis of
      complex gangliosides, suppresses BACE1 degradation and modulates APP processing.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia characterized by
      the extracellular accumulation of amyloid beta (Abeta) peptides, which are
      produced by proteolytic cleavages of amyloid precursor protein (APP).
      Gangliosides are involved in AD pathophysiology including Abeta deposition and
      APP processing, yet the detailed mechanisms are not fully understood. Here we
      examined how changes in the carbohydrate moiety of gangliosides alter APP
      processing in human melanoma cells, neuroectoderm-derived cells. We showed that
      forced expression of GD2, GM2 or GM1 (by introducing B4GALNT1 cDNA into cells not
      expressing this glycosyltransferase) results in increases of alpha- and beta-site
      cleavages of APP with a prominent increase in beta-cleavage. We also showed that
      beta-site APP cleaving enzyme 1 (BACE1) protein is highly protected from the
      degradation in cells expressing these gangliosides, thereby increasing the
      expression of this protein. Unexpectedly, adding gangliosides exogenously altered
      neither BACE1 levels nor beta-site cleavage. The stabilisation of BACE1 protein
      led to the increase of this protein in lipid rafts, where BACE1 processes APP.
      Based on the current results, we propose a hitherto undisclosed link between
      ganglioside expression and AD; the expression of B4GALNT1 positively regulates
      the beta-site cleavage by mainly inhibiting the lysosomal degradation of BACE1
      protein.

PMID- 27687692
TI  - T-cell subsets in lymph nodes identify a subgroup of follicular lymphoma patients
      with favorable outcome.
AB  - We have analyzed in lymph nodes at diagnosis of 75 patients with follicular
      lymphoma (FL) the relationship between different T-cell subpopulations, assessed
      by immunohistochemistry (IHC) and flow cytometry (FC), with the outcome. CD4+
      cells were the most abundant T-cells in tumor tissue sections, whilst CD57+ cells
      were the less frequent. In addition to nonambulatory performance status, advanced
      stage and FLIPI, low CD4+CD57+/CD4+ ratio (p = .041), and low CD4+/CD8+ ratio (p
      = .008) predicted poor overall survival (OS). Multivariate analysis showed that
      CD4+CD57+/CD4+ ratio was the most important variable for OS. In conclusion, T
      cell subpopulations, including CD4+CD57+/CD4+ ratio analyzed by FC, could
      identify FL patients with favorable outcome.

PMID- 27687694
TI  - Notice of Changes to Compleat Pediatric 1.0.
AB  - Samela K, Mokha J, Emerick K, Davidovics ZH. Transition to a tube feeding formula
      with real food ingredients in pediatric patients with intestinal failure
      [published online August 4, 2016]. Nutr Clin Pract. (Original DOI:
      10.1177/0884533616661011 ) After publication of this article OnlineFirst, the
      authors learned that Nestle Health Sciences has changed the product formulation
      of Compleat Pediatric 1.0 by adding ingredients such as FOS, pea protein, and
      inulin that were not part of the product during our review. While the authors
      stand by their results with the original Compleat Pediatric 1.0, these results
      may not be reproducible with the new product formulation. The article has been
      updated to include this acknowledgment.

PMID- 27687693
TI  - Incipient ferroelectricity of water molecules confined to nano-channels of beryl.
AB  - Water is characterized by large molecular electric dipole moments and strong
      interactions between molecules; however, hydrogen bonds screen the dipole-dipole
      coupling and suppress the ferroelectric order. The situation changes drastically
      when water is confined: in this case ordering of the molecular dipoles has been
      predicted, but never unambiguously detected experimentally. In the present study
      we place separate H2O molecules in the structural channels of a beryl single
      crystal so that they are located far enough to prevent hydrogen bonding, but
      close enough to keep the dipole-dipole interaction, resulting in incipient
      ferroelectricity in the water molecular subsystem. We observe a ferroelectric
      soft mode that causes Curie-Weiss behaviour of the static permittivity, which
      saturates below 10 K due to quantum fluctuations. The ferroelectricity of water
      molecules may play a key role in the functioning of biological systems and find
      applications in fuel and memory cells, light emitters and other nanoscale
      electronic devices.

PMID- 27687695
TI  - Canthaxanthin: From molecule to function.
AB  - The aim of this review is to summarize the relevant literature about the use of
      canthaxanthin in food science and nutrition research. Canthaxanthin is a red
      orange carotenoid that belongs to the xanthophyll group. This naturally occurring
      pigment is present in bacteria, algae and some fungi. Canthaxanthin is also
      responsible for the color of flamingo feathers, koi carp skin and crustacean
      shells. Canthaxanthin is widely used in poultry (broiler, laying hens) as a feed
      additive. Canthaxanthin can be obtained by total synthesis. The canthaxanthin
      mediated color of foods is an important quality criterion for consumers.
      Recently, the potential health-promoting effects of canthaxanthin have been
      discussed. Canthaxanthin enrichment of LDL has the potential to protect
      cholesterol from oxidation. In addition to its free radical scavenging and
      antioxidant properties (e.g., the induction of catalase and superoxide
      dismutase), canthaxanthin's immunomodulatory activity (e.g., enhancing the
      proliferation and function of immune competent cells) and its important role in
      gap junction communication (e.g., induction of the transmembrane protein connexin
      43) have been reported. Many studies regarding the potential health benefits of
      canthaxanthin have been conducted in vitro and should be validated in appropriate
      in vivo models.

PMID- 27687696
TI  - Efficient and Tunable Three-Dimensional Functionalization of Fully Zwitterionic
      Antifouling Surface Coatings.
AB  - To enhance the sensitivity and selectivity of surface-based (bio)sensors, it is
      of crucial importance to diminish background signals that arise from the
      nonspecific binding of biomolecules, so-called biofouling. Zwitterionic polymer
      brushes have been shown to be excellent antifouling materials. However, for
      sensing purposes, antifouling does not suffice but needs to be combined with the
      possibility to efficiently modify the brush with recognition units. So far this
      has been achieved only at the expense of either antifouling properties or binding
      capacity. Herein we present a conceptually new approach by integrating both
      characteristics into a single tailor-made monomer: a novel sulfobetaine-based
      zwitterionic monomer equipped with a clickable azide moiety. Copolymerization of
      this monomer with a well-established standard sulfobetaine monomer results in
      highly antifouling surface coatings with a large yet tunable number of clickable
      groups present throughout the entire brush. Subsequent functionalization of the
      azido brushes via widely used strain-promoted alkyne azide click reactions yields
      fully zwitterionic 3D-functionalized coatings with a recognition unit of choice
      that can be tailored for any specific application. Here we show a proof of
      principle with biotin-functionalized brushes on Si3N4 that combine excellent
      antifouling properties with specific avidin binding from a protein mixture. The
      signal-to-noise ratio is significantly improved over that of traditional chain
      end modification of sulfobetaine polymer brushes, even if the azide content is
      lowered to 1%. This therefore offers a viable approach to the development of
      biosensors with greatly enhanced performance on any surface.

PMID- 27687697
TI  - Widespread DNA hypomethylation and differential gene expression in Turner
      syndrome.
AB  - Adults with 45,X monosomy (Turner syndrome) reflect a surviving minority since
      more than 99% of fetuses with 45,X monosomy die in utero. In adulthood 45,X
      monosomy is associated with increased morbidity and mortality, although
      strikingly heterogeneous with some individuals left untouched while others suffer
      from cardiovascular disease, autoimmune disease and infertility. The present
      study investigates the leukocyte DNAmethylation profile by using the 450K
      Illumina Infinium assay and the leukocyte RNA-expression profile in 45,X monosomy
      compared with karyotypically normal female and male controls. We present results
      illustrating that genome wide X-chromosome RNA-expression profile, autosomal DNA
      methylation profile, and the X-chromosome methylation profile clearly distinguish
      Turner syndrome from controls. Our results reveal genome wide hypomethylation
      with most differentially methylated positions showing a medium level of
      methylation. Contrary to previous studies, applying a single loci specific
      analysis at well-defined DNA loci, our results indicate that the hypomethylation
      extend to repetitive elements. We describe novel candidate genes that could be
      involved in comorbidity in TS and explain congenital urinary malformations
      (PRKX), premature ovarian failure (KDM6A), and aortic aneurysm formation (ZFYVE9
      and TIMP1).

PMID- 27687698
TI  - Evaluation of intraosseous sampling for measurements of alanine aminotransferase,
      alkaline phosphatase, aspartate aminotransferase, creatinine kinase, gamma
      glutamyl transferase and lactate dehydrogenase.
AB  - BACKGROUND: Intraosseous (IO) access can be established faster than a venous or
      arterial access when there is an urgent need for rapid initiation of treatment.
      The access can also be used to draw marrow samples. The aim of the present study
      was to evaluate the potential use of IO samples for enzyme determinations using a
      porcine model. MATERIALS AND METHODS: Bilateral tibial intraosseous cannulae and
      an arterial catheter were used for blood sampling from five healthy anesthetized
      pigs. Samples were collected at baseline and thereafter hourly for 6 h and
      analyzed for alanine aminotransferase, alkaline phosphatase, aspartate
      aminotransferase, creatinine kinase, gamma-glutamyl transferase and lactate
      dehydrogenase. RESULTS: Creatinine kinase, lactate dehydrogenase and alkaline
      phosphatase levels decreased over time. The differences between IO and arterial
      sampling were limited for all studied markers. CONCLUSION: The correlation
      between marrow and blood analysis for liver function tests and CK is sufficiently
      accurate in an emergency situation.

PMID- 27687699
TI  - The Effect of Aluminum Exposure on Reproductive Ability in the Bank Vole (Myodes
      glareolus).
AB  - Human impact on the environment is steadily increasing the amounts of aluminum in
      the ecosystems. This element accumulates in plants and water, potentially
      exposing herbivores to its harmful effect. In heavily polluted sites, a decrease
      in the density of small rodent populations has been observed. This decline may be
      caused by many factors, including decreased fertility. The aim of the presented
      research was to determine how aluminum, administered at concentrations similar to
      those recorded in industrial districts (Al I = 3 mg/l, Al II = 200 mg/l), affects
      the reproductive abilities of small rodents. As the indicators of reproductive
      abilities, body weight, weight of the testes and accessory sex glands of males,
      and uterus weight of females were estimated. In females, the number of matured
      follicles (types 6, 7, and 8) was analyzed, while in males, the quantity and
      quality (matured, viable, swollen, motile, head abnormalities) of epididymal
      sperm cells were assessed. Moreover, the development of testes, measured by
      spermatogenic index, was determined. The model species was the bank vole. Our
      results have proven that aluminum impairs adult individuals' reproductive
      abilities by decreasing the quality and quantity of sperm cells and by causing
      morphologically abnormal development of the gonads. However, no difference in
      male organometric parameters was found, and only in females treated with 3 mg/l
      Al, the uterus weight was higher than control. No differences were found in the
      total number of matured follicles. These results suggest that the decline in
      rodent numbers in industrial districts is due, at least in part, to poorer males'
      reproductive abilities, resulting from exposure to aluminum contamination.

PMID- 27687700
TI  - Determine Multiple Elements Simultaneously in the Sera of Umbilical Cord Blood
      Samples-a Very Simple Method.
AB  - Analyzing the concentrations of heavy metals in the sera of umbilical cord blood
      samples can provide useful information about prenatal exposure to environmental
      agents. An analytical method based on ICP-MS to simultaneously determine multiple
      elements in umbilical cord blood samples was developed for assessing the in utero
      exposure to metallic and metalloid elements. The method only required as little
      as 100 MUL of serum diluted 1:25 for direct analysis. Matrix-matched protocol was
      used to eliminate mass matrix interference and kinetic energy discrimination mode
      was used to eliminate the polyatomic ion interference. The assay was completed on
      average within 4 min with the detection limits ranging from 0.0002 to 44.4 MUg/L
      for all the targeted elements. The detection rates for most of elements were 100
      % other than cadmium (Cd), lead (Pb), and mercury (Hg). The testing results of
      the certified reference materials were ideal. The method is simple and sensitive,
      so it is suitable for the monitoring of large quantities of samples.

PMID- 27687701
TI  - Aberrant iron metabolism might have an impact on progression of diseases in
      Tsumura Suzuki obese diabetes mice, a model of spontaneous metabolic syndrome.
AB  - Tsumura Suzuki obese diabetes (TSOD) mice spontaneously develop obesity and type
      2 diabetes with aberrant accumulation of excessive iron in the spleen. Aberrantly
      accumulated iron may cause oxidative stress and result in various symptoms of
      metabolic syndrome in the mice. We investigated iron metabolism and oxidative
      stress in TSOD mice. Male TSOD and control mice were killed at 2, 3, 6, and 8
      months of age, and blood and tissue samples were collected. The serum levels of
      ferritin and oxidized low-density lipoprotein (OxLDL) were measured. Total
      glutathione concentrations of liver and spleen were also measured. Serum ferritin
      and OxLDL were higher in TSOD mice than in control mice at 2 and 6 months. In
      addition, the glutathione concentrations in TSOD mice were lower in the liver and
      higher in the spleen at 3 and 6 months than those in control mice. These results
      suggest that abnormal iron metabolism and imbalanced oxidative stress occurs in
      young and old TSOD mice. We propose herein that TSOD mice might be a unique and
      valuable model for investigating the role of iron metabolism in pathogenesis of
      metabolic syndrome.

PMID- 27687702
TI  - Incremental value of live/real time three-dimensional transthoracic
      echocardiography over the two-dimensional technique in assessing carcinoid heart
      disease involving the aortic valve.
AB  - We present a case of an adult with metastatic carcinoid heart disease, in whom
      live/real time three-dimensional transthoracic echocardiography provided
      incremental value over two-dimensional transthoracic echocardiography in
      assessing involvement of the aortic valve.

PMID- 27687703
TI  - Negative beliefs about low back pain are associated with persistent high
      intensity low back pain.
AB  - While previous cross-sectional studies have found that negative beliefs about low
      back pain are associated with pain intensity, the relationship between back
      beliefs and persistent low back pain is not well understood. This cohort study
      aimed to examine the role of back beliefs in persistent low back pain in
      community-based individuals. A hundred and ninety-two participants from a
      previous musculoskeletal health study were invited to take part in a two-year
      follow-up study. Beliefs about back pain were assessed by the Back Beliefs
      Questionnaire (BBQ) at baseline and low back pain intensity was measured by the
      Chronic Pain Grade Questionnaire at baseline and follow-up. Of the 150
      respondents (78.1%), 16 (10.7%) reported persistent high intensity low back pain,
      12 (8.0%) developed high intensity low back pain, in 16 (10.7%) their high
      intensity low back pain resolved and 106 (70.7%) experienced no high intensity
      low back pain. While participants were generally positive about low back pain
      (BBQ mean (SD) = 30.2 (6.4)), those with persistent high intensity pain reported
      greater negativity (BBQ mean (SD) = 22.6 (4.9)). Negative beliefs about back pain
      were associated with persistent high intensity low back pain after adjusting for
      confounders (M (SE) = 23.5 (1.6) vs. >30.1 (1.7), p < .001). This study found
      negative back beliefs were associated with persistent high intensity low back
      pain over 2 years in community-based individuals. While further longitudinal
      studies are required, these findings suggest that targeting beliefs in programs
      designed to treat and prevent persistent high intensity low back pain may be
      important.

PMID- 27687704
TI  - In situ DART-MS as a Versatile and Rapid Dereplication Tool in Lichenology:
      Chemical Fingerprinting of Ophioparma ventosa.
AB  - INTRODUCTION: Lichens widely occur all over the world and are known to produce
      unique secondary metabolites with various biological activities. OBJECTIVE: To
      develop high-throughput screening approaches requiring little to no sample
      preparation to alleviate the dereplication holdup and accelerate the discovery
      workflow of new structures from lichens. METHODOLOGY: The extracellular
      distribution of lichen metabolites is incentive for in situ chemical profiling of
      lichens using the ambient mass spectrometry DART-MS. For this purpose, the
      chlorolichen Ophioparma ventosa, producing an array of lichen polyphenolics that
      encompass the main structural classes associated to lichen chemodiversity,
      represented a relevant model to assess the versatility of this platform. The
      feasibility of this approach was first established by analysing the pure
      compounds known from this species prior to being extended to different solid
      organs of the lichen. RESULTS: All tested compounds could be detected in positive
      and negative ion modes, most often with prevalent protonated or deprotonated
      molecules. Only depsides underwent a significant in-source fragmentation in both
      ionisation modes, which should be regarded as an added value for their structural
      elucidation. In situ DART-MS analyses of Ophioparma ventosa provided an extensive
      chemical profile and noteworthy pinpointed miriquidic acid, an unusual lichen
      depside so far unknown within this species. At last, in situ DART-MS granted a
      first insight into the distribution of the metabolites within the lichen.
      CONCLUSION: DART-MS represents a versatile tool to the wide field of lichenology,
      facilitating accelerated and sharp analyses of lichens and bypassing costly and
      tedious procedures of solvent extraction. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 27687705
TI  - In silico analysis and expression studies of kisspeptin gene in C. catla.
AB  - We report the characterization of kisspeptin gene which is considered to be
      essential for successful animal reproduction. The full-length cDNA sequence of
      kiss2 was 583 bp, consisted of 11 bp 5'-UTR (untranslated region) and 194 bp 3'
      UTR, respectively. Open reading frame of 378 bp encoding a putative protein of
      125 amino acids. The Catla catla kiss2 protein was having a molecular weight of
      14.51 kDa and isoelectric point (pI) of 8.46. There were four serine (Ser), four
      threonine (Thr) and two tyrosine (Tyr) phosphorylation sites and no N
      glycosylation sites on the predicted protein. The amino acids on positions 8, 11,
      24, 80 and 114 were detected to be ligand binding sites. The signal peptide
      analysis predicted that C. catla kiss2 is a secretory protein. Kiss2 protein is
      localized in nuclear region (49.7%) and the extracellular region (38.3%) of the
      cell. Analysis of tissue distribution revealed that, kiss2 transcripts were
      predominantly expressed in the brain and gonads, with expression levels in female
      higher than those of male. Ontogenetic analysis of kiss2 demonstrated that
      expression level was low during early phase of development stages and more
      expression was observed during mature stage. Overall present results lay a strong
      basis for understanding the role of kisspeptin in the neuroendocrine system in
      teleosts.

PMID- 27687707
TI  - Preparation, characterization, and pharmacokinetics of tilmicosin- and
      florfenicol-loaded hydrogenated castor oil-solid lipid nanoparticles.
AB  - To effectively control bovine mastitis, tilmicosin (TIL)- and florfenicol (FF)
      loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil (HCO) were
      prepared by a hot homogenization and ultrasonication method. In vitro
      antibacterial activity, properties, and pharmacokinetics of the TIL-FF-SLN were
      studied. The results demonstrated that TIL and FF had a synergistic or additive
      antibacterial activity against Streptococcus dysgalactiae, Streptococcus uberis,
      and Streptococcus agalactiae. The size, polydispersity index, and zeta potential
      of nanoparticles were 289.1 +/- 13.7 nm, 0.31 +/- 0.05, and -26.7 +/- 1.3 mV,
      respectively. The encapsulation efficiencies for TIL and FF were 62.3 +/- 5.9%
      and 85.1 +/- 5.2%, and the loading capacities for TIL and FF were 8.2 +/- 0.6%
      and 3.3 +/- 0.2%, respectively. The TIL-FF-SLN showed no irritation in the
      injection site and sustained release in vitro. After medication, TIL and FF could
      maintain about 0.1 MUg/mL for 122 and 6 h. Compared to the control solution, the
      SLN increased the area under the concentration-time curve (AUC0-t ), elimination
      half-life (T1/2ke ), and mean residence time (MRT) of TIL by 33.09-, 23.29-, and
      37.53-fold, and 1.69-, 5.00-, and 3.83-fold for FF, respectively. These results
      of this exploratory study suggest that the HCO-SLN could be a useful system for
      the delivery of TIL and FF for bovine mastitis therapy.

PMID- 27687706
TI  - Ketamine-induced inhibition of glycogen synthase kinase-3 contributes to the
      augmentation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      receptor signaling.
AB  - OBJECTIVES: Sub-anesthetic doses of ketamine have been found to provide rapid
      antidepressant actions, indicating that the cellular signaling systems targeted
      by ketamine are potential sites for therapeutic intervention. Ketamine acts as an
      antagonist of N-methyl-D-aspartate (NMDA) receptors, and animal studies indicate
      that subsequent augmentation of signaling by alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) receptors is critical for the
      antidepressant outcome. METHODS: In this study, we tested if the inhibitory
      effect of ketamine on glycogen synthase kinase-3 (GSK3) affected hippocampal cell
      surface AMPA receptors using immunoblotting of membrane and synaptosomal extracts
      from wild-type and GSK3 knockin mice. RESULTS: Treatment with an antidepressant
      dose of ketamine increased the hippocampal membrane level of the AMPA glutamate
      receptor (GluA)1 subunit, but did not alter the localization of GluA2, GluA3, or
      GluA4. This effect of ketamine was abrogated in GSK3 knockin mice expressing
      mutant GSK3 that cannot be inhibited by ketamine, demonstrating that ketamine
      induced inhibition of GSK3 is necessary for up-regulation of cell surface AMPA
      GluA1 subunits. AMPA receptor trafficking is regulated by post-synaptic density
      95 (PSD-95), a substrate for GSK3. Ketamine treatment decreased the hippocampal
      membrane level of phosphorylated PSD-95 on Thr-19, the target of GSK3 that
      promotes AMPA receptor internalization. CONCLUSIONS: These results demonstrate
      that ketamine-induced inhibition of GSK3 causes reduced phosphorylation of PSD
      95, diminishing the internalization of AMPA GluA1 subunits to allow for augmented
      signaling through AMPA receptors following ketamine treatment.

PMID- 27687710
TI  - Junior doctors say what BMA should do now to stop the new contract.

PMID- 27687709
TI  - Performance validity in undergraduate research participants: a comparison of
      failure rates across tests and cutoffs.
AB  - OBJECTIVE: This study compared failure rates on performance validity tests (PVTs)
      across liberal and conservative cutoffs in a sample of undergraduate students
      participating in academic research. METHOD: Participants (n = 120) were
      administered four free-standing PVTs (Test of Memory Malingering, Word Memory
      Test, Rey 15-Item Test, Hiscock Forced-Choice Procedure) and three embedded PVTs
      (Digit Span, letter and category fluency). Participants also reported their
      perceived level of effort during testing. RESULTS: At liberal cutoffs, 36.7% of
      the sample failed >=1 PVTs, 6.7% failed >=2, and .8% failed 3. At conservative
      cutoffs, 18.3% of the sample failed >=1 PVTs, 2.5% failed >=2, and .8% failed 3.
      Participants were 3 to 5 times more likely to fail embedded (15.8-30.8%) compared
      to free-standing PVTs (3.3-10.0%). There was no significant difference in failure
      rates between native and non-native English speaking participants at either
      liberal or conservative cutoffs. Additionally, there was no relation between self
      reported effort and PVT failure rates. CONCLUSIONS: Although PVT failure rates
      varied as a function of PVTs and cutoffs, between a third and a fifth of the
      sample failed >=1 PVTs, consistent with high initial estimates of invalid
      performance in this population. Embedded PVTs had notably higher failure rates
      than free-standing PVTs. Assuming optimal effort in research using students as
      participants without a formal assessment of performance validity introduces a
      potentially significant confound in the study design.

PMID- 27687711
TI  - Of making many books there is no end: the development of the developmental
      literature.

PMID- 27687708
TI  - Multi-perspective quality control of Illumina RNA sequencing data analysis.
AB  - Quality control (QC) is a critical step in RNA sequencing (RNA-seq). Yet, it is
      often ignored or conducted on a limited basis. Here, we present a multi
      perspective strategy for QC of RNA-seq experiments. The QC of RNA-seq can be
      divided into four related stages: (1) RNA quality, (2) raw read data (FASTQ), (3)
      alignment and (4) gene expression. We illustrate the importance of conducting QC
      at each stage of an RNA-seq experiment and demonstrate our recommended RNA-seq QC
      strategy. Furthermore, we discuss the major and often neglected quality issues
      associated with the three major types of RNA-seq: mRNA, total RNA and small RNA.
      This RNA-seq QC overview provides comprehensive guidance for researchers who
      conduct RNA-seq experiments.

PMID- 27687712
TI  - Functional outcome in 17 patients whose mandibles were reconstructed with free
      fibular flaps.
AB  - OBJECTIVE: The vascularised free fibular flap is considered to be a reliable
      choice for reconstruction of oromandibular defects, especially after resection of
      malignant tumours in the area. This study evaluates the functional outcome of
      this method. METHOD: From January 2001 - May 2014, 37 patients were treated at
      the University Hospital of Linkoping using the free fibular flap. The authors
      present the results from 17. This study reviewed their records and used the
      University of Washington Quality-of-Life questionnaire (UW-QoL), the Head and
      Neck Performance Status Scale (PSS), and interviews to assess their outcome.
      RESULTS AND CONCLUSIONS: Functional evaluation showed a significant decrease in
      chewing (16 out of 17 patients), appearance (n = 10), salivation (n = 6),
      sensitivity in the mouth and skin (n = 16), occlusive problems in the mouth (n =
      13), and range of mouth opening (n = 12). The remaining domains showed acceptable
      results, although most of them probably could not compare with the preoperative
      function. Out of 17 patients, six had to adjust their eating in public
      significantly, three thought their activity to be considerably restricted and two
      their recreation to be notably diminished. Common postoperative complications
      were infections or fistula in the mandible (n = 6), partial or complete rejection
      of the cutaneous flap (n = 4), and rupture of some of the sutures (n = 3). Nine
      patients required at least one more operation to repair defects, and six required
      a new soft tissue flap.

PMID- 27687714
TI  - Comparison of post-authorisation measures from regulatory authorities with
      additional evidence requirements from the HTA body in Germany - are additional
      data requirements by the Federal Joint Committee justified?
AB  - OBJECTIVES: The aim of this study was to compare post-authorisation measures
      (PAMs) from the European Medicines Agency (EMA) with data requests in fixed
      termed conditional appraisals of early benefit assessments from the German
      Federal Joint Committee (G-BA). METHODS: Medicinal products with completed
      benefit assessments during an assessment period of 3.5 years were considered.
      PAMs extracted from European Public Assessment Reports (EPARs) were compared with
      data requests issued by the G-BA in the context of conditional appraisals.
      RESULTS: Twenty conditional appraisals (19 products) and 34 EPARs containing PAMs
      (33 products) were identified. Data categories (efficacy, safety, etc.), data
      types (type of study required to address the request) and clarity of requests
      were determined. Conditional appraisals disproportionately focused on oncology
      products (13/19 products with conditional appraisals vs. 14/33 products with
      PAMs). No clear rationale for the G-BA issuing conditional appraisals could be
      identified in public sources. Both EMA and G-BA requested mainly efficacy and
      safety data (44/54 and 23/35 categories requested, respectively); however, 28/35
      G-BA data requirements went beyond requests made by the EMA. Almost half of the G
      BA requests (9/20), but no PAMs, were unclear, and no methodological guidance for
      fulfilling the data requirements was provided by the G-BA. CONCLUSIONS: Better
      alignment between data requests from regulatory authorities and health technology
      assessment bodies is strongly recommended.

PMID- 27687715
TI  - Voxel-wise grey matter asymmetry analysis in left- and right-handers.
AB  - Handedness is thought to originate in the brain, but identifying its structural
      correlates in the cortex has yielded surprisingly incoherent results. One idea
      proclaimed by several authors is that structural grey matter asymmetries might
      underlie handedness. While some authors have found significant associations with
      handedness in different brain areas (e.g. in the central sulcus and precentral
      sulcus), others have failed to identify such associations. One method used by
      many researchers to determine structural grey matter asymmetries is voxel based
      morphometry (VBM). However, it has recently been suggested that the standard VBM
      protocol might not be ideal to assess structural grey matter asymmetries, as it
      establishes accurate voxel-wise correspondence across individuals but not across
      both hemispheres. This could potentially lead to biased and incoherent results.
      Recently, a new toolbox specifically geared at assessing structural asymmetries
      and involving accurate voxel-wise correspondence across hemispheres has been
      published [F. Kurth, C. Gaser, E. Luders. A 12-step user guide for analyzing
      voxel-wise gray matter asymmetries in statistical parametric mapping (SPM), Nat
      Protoc 10 (2015), 293-304]. Here, we used this new toolbox to re-assess grey
      matter asymmetry differences in left- vs. right-handers and linked them to
      quantitative measures of hand preference and hand skill. While we identified
      several significant left-right asymmetries in the overall sample, no difference
      between left- and right-handers reached significance after correction for
      multiple comparisons. These findings indicate that the structural brain
      correlates of handedness are unlikely to be rooted in macroscopic grey matter
      area differences that can be assessed with VBM. Future studies should focus on
      other potential structural correlates of handedness, e.g. structural white matter
      asymmetries.

PMID- 27687713
TI  - Walking performance is positively correlated to calf muscle fiber size in
      peripheral artery disease subjects, but fibers show aberrant mitophagy: an
      observational study.
AB  - BACKGROUND: Patients with lower extremity peripheral artery disease (PAD) have
      decreased mobility, which is not fully explained by impaired blood supply to the
      lower limb. Additionally, reports are conflicted regarding fiber type
      distribution patterns in PAD, but agree that skeletal muscle mitochondrial
      respiration is impaired. METHODS: To test the hypothesis that reduced muscle
      fiber oxidative activity and type I distribution are negatively associated with
      walking performance in PAD, calf muscle biopsies from non-PAD (n = 7) and PAD
      participants (n = 26) were analyzed immunohistochemically for fiber type and
      size, oxidative activity, markers of autophagy, and capillary density. Data were
      analyzed using analysis of covariance. RESULTS: There was a wide range in fiber
      type distribution among subjects with PAD (9-81 % type I fibers) that did not
      correlate with walking performance. However, mean type I fiber size correlated
      with 4-min normal- and fastest-paced walk velocity (r = 0.4940, P = 0.010 and r =
      0.4944, P = 0.010, respectively). Although intensity of succinate dehydrogenase
      activity staining was consistent with fiber type, up to 17 % of oxidative fibers
      were devoid of mitochondria in their cores, and the core showed accumulation of
      the autophagic marker, LC3, which did not completely co-localize with LAMP2, a
      lysosome marker. CONCLUSIONS: Calf muscle type I fiber size positively correlates
      with walking performance in PAD. Accumulation of LC3 and a lack of co
      localization of LC3 with LAMP2 in the area depleted of mitochondria in PAD fibers
      suggests impaired clearance of damaged mitochondria, which may contribute to
      reduced muscle oxidative capacity. Further study is needed to determine whether
      defective mitophagy is associated with decline in function over time, and whether
      interventions aimed at preserving mitochondrial function and improving autophagy
      can improve walking performance in PAD.

PMID- 27687716
TI  - Changes in nitric oxide synthase isoforms in the trigeminal ganglion of rat
      following chronic tooth pulp inflammation.
AB  - Nitric oxide (NO) possibly plays an important role in the events resulting in
      hyperalgesia. NO synthase (NOS) is a key enzyme in the production of NO. Changes
      in NOS expression in primary sensory neurons may be involved in the persistent
      sensory abnormalities that can be induced by inflammation. To assess the possible
      roles of NOS in trigeminal sensory system, we studied changes in the expression
      of NOS isoforms in the trigeminal ganglion (TG) following chronic inflammation
      after pulp exposure (PX) in rats. The neurons innervating injured tooth in the TG
      were labeled by fluoro-gold (FG). Immunohistochemical staining was used to reveal
      the presence of NOS. The results showed that within the FG-labeled population,
      neuron counts revealed a significant increase in the proportion of NOS neurons
      following PX, in which the frequency of iNOS and nNOS-positive neurons started to
      increase at 3 and 7day, respectively, and peaked at 28day. There was no eNOS
      expression observed in the control group and PX-treated groups. The results
      demonstrate that PX-induced chronic pulpal inflammation results in significant
      increase of nNOS and iNOS in the TG. It suggests that nNOS and iNOS could be
      involved in mediation of peripheral processing of nociceptive information
      following chronic tooth pulp inflammation.

PMID- 27687717
TI  - DNAJC6 mutations are not common causes of early onset Parkinson's disease in
      Chinese Han population.
AB  - DNAJC6 has been reported as a causative gene for early onset Parkinson's disease
      (EOPD) in some populations, and different mutations have been reported to be
      associated with EOPD. However, Until now, there is limited information about
      DNAJC6 gene test in sporadic EOPD patients in Chinese population. Herein, we
      performed comprehensive DNAJC6 mutation screenings in 117 EOPD patients from
      Chinese population. None of the reported disease-causing mutations were found.
      However, we identified a novel non-synonymous heterozygous variant c.2798T>C
      (p.Val933Ala). Bioinformatics analysis demonstrate that the c.2798T>C variant
      exhibits highly conserved residues across species. Our data suggests that DNAJC6
      mutations are not common causes of EOPD in Chinese population.

PMID- 27687718
TI  - Epigenetic legacy of parental experiences: Dynamic and interactive pathways to
      inheritance.
AB  - The quality of the environment experienced by an individual across his or her
      lifespan can result in a unique developmental trajectory with consequences for
      adult phenotype and reproductive success. However, it is also evident that these
      experiences can impact the development of offspring with continued effect on
      subsequent generations. Epigenetic mechanisms have been proposed as a mediator of
      both these within- and across-generation effects, and there is increasing
      evidence to support the role of environmentally induced changes in DNA
      methylation, posttranslational histone modifications, and noncoding RNAs in
      predicting these outcomes. Advances in our understanding of these molecular
      modifications contribute to increasingly nuanced perspectives on plasticity and
      transmission of phenotypes across generations. A challenge that emerges from this
      research is in how we integrate these "new" perspectives with traditional views
      of development, reproduction, and inheritance. This paper will highlight evidence
      suggestive of an epigenetic impact of the environment on mothers, fathers, and
      their offspring, and illustrate the importance of considering the dynamic nature
      of reproduction and development and inclusive views of inheritance within the
      evolving field of behavioral and environmental epigenetics.

PMID- 27687719
TI  - The role of p38MAPK activation in spinal dorsal horn in remifentanil-induced
      postoperative hyperalgesia in rats.
AB  - OBJECTIVES: Remifentanil may induce hyperalgesia. Recent studies implicate a
      close relationship between post-surgical hyperalgesia and phosphorylation and
      activation of p38 mitogen-activated protein kinase (p38MAPK) in the spinal
      microglia. This study aimed to investigate whether the combination of post
      surgical and remifentanil-induced hyperalgesia worsens post-operative pain and
      whether phosphorylated p38MAPK (phospho-p38MAPK) in the spinal dorsal horn in
      rats is involved in remifentanil-induced postoperative hyperalgesia. METHODS:
      Sprague-Dawley rats were randomly divided into six groups: control, incision
      only, remifentanil only, remifentanil + incision, remifentanil + incision +
      SB203580, and remifentanil + incision + DMSO. The p38MAPK inhibitor SB203580 and
      DMSO were injected intrathecally. A right plantar surgical incision was performed
      in the incision groups, and remifentanil was infused for 60 min in the
      remifentanil groups. Mechanical paw withdrawal threshold (PWT) and thermal paw
      withdrawal latency (PWL) of the bilateral hind paws were measured and the number
      of phospho-p38MAPK-positive cells in rat spinal dorsal horn sections was counted.
      RESULTS: Intravenous remifentanil infusion decreased bilateral plantar PWL values
      from 1 h to 3 days after surgery, however there was no additive effect with
      incision-induced values. There was a significant increase in the number of dorsal
      horn phospho-p38MAPK-positive cells in the remifentanil + incision group compared
      to the incision group, but no increase in the number of these cells when
      remifentanil was given alone. Intrathecal pretreatment with SB203580 attenuated
      remifentanil + incision-induced postoperative hyperalgesia and significantly
      reduced activation of phospho-p38MAPK in spinal dorsal horn. CONCLUSIONS:
      Incision-induced and remifentanil-induced increases in hyperalgesia were not
      additive when incision and remifentanil were used together. Data on phospho
      38MAPK activation in remifenanil-induced hyperalgesia were contradictory and need
      further clarification.

PMID- 27687720
TI  - Prevention of Critical Care Complications in the Coronary Intensive Care Unit:
      Protocols, Bundles, and Insights From Intensive Care Studies.
AB  - Over the past half century, coronary care units have expanded from specialized
      ischemia arrhythmia monitoring units into intensive care units (ICUs) for acutely
      ill and medically complex patients with a primary cardiac diagnosis. Patients
      admitted to contemporary coronary intensive care units (CICUs) are at risk for
      common and preventable critical care complications, yet many CICUs have not
      adopted standard-of-care prevention protocols and practices from general ICUs. In
      this article, we (1) review evidence-based interventions and care bundles that
      reduce the incidence of ventilator-associated pneumonia, excess sedation during
      mechanical ventilation, central line infections, stress ulcers, malnutrition,
      delirium, and medication errors and (2) recommend pragmatic adaptations for
      common conditions in critically ill patients with cardiac disease, and (3)
      provide example order sets and practical CICU protocol implementation strategies.

PMID- 27687721
TI  - Hemodynamic Evaluation of Vasomotion: Capacitance vs Conductance.

PMID- 27687722
TI  - Evaluation of the effects and adverse drug reactions of low-dose dexamethasone
      premedication with weekly docetaxel.
AB  - PURPOSE: A weekly docetaxel regimen had comparable efficacy with a tri-weekly
      schedule and caused significantly less severe neutropenia and febrile
      neutropenia. Therefore, a weekly docetaxel regimen has become increasingly common
      in cancer treatment. Premedication with corticosteroids can effectively prevent
      or reduce the severity of hypersensitivity and fluid retention. However, no
      recommended steroid dosage for a weekly docetaxel regimen has been established to
      date. The aim of this study is to compare the efficacy and complications of two
      different weekly docetaxel premedication protocols. METHODS: We retrospectively
      compared the hypersensitivity, hyperglycemia, and infection incidence associated
      with two weekly docetaxel premedication protocols. The control group
      (dexamethasone 10 mg intravenously and 4 mg orally every 12 h for four doses,
      starting 1 h before docetaxel administration) patients started weekly docetaxel
      chemotherapy between May 2012 and April 2013 at Seoul National University
      Hospital, and the experimental group (dexamethasone 10 mg intravenously 1 h prior
      to each docetaxel administration) patients started weekly docetaxel chemotherapy
      between May 2013 and April 2014. RESULTS: In total, 109 patients in the control
      group and 97 patients in the experimental group were included in this study, and
      there were no statistically significant differences in baseline characteristics
      between the two groups. The incidence of hypersensitivity and hyperglycemia were
      similar, but infections were observed significantly less in the experimental
      group (p = 0.020, OR = 0.408, 0.0190-0.0879). CONCLUSIONS: A low-dose
      dexamethasone premedication protocol has comparable efficacy in the prevention of
      docetaxel hypersensitivity with fewer infection complications. Therefore, we
      recommend a low-dose dexamethasone premedication protocol for weekly docetaxel
      regimens.

PMID- 27687723
TI  - Residential road traffic noise exposure and survival after breast cancer - A
      cohort study.
AB  - BACKGROUND: It is generally acknowledged that patients with already existing
      clinical conditions are especially vulnerable to the effects of traffic noise
      exposure. The aim of the present study was to investigate the association between
      residential road traffic noise and breast cancer survival. METHODS: Road traffic
      noise was calculated for all residential addresses from 1987 to February 2012 for
      incident breast cancer cases (n=1,759) in a cohort of 57,053 Danes. We used Cox
      Proportional Hazard Models to investigate the association between residential
      road traffic noise at different time-windows, and overall and breast cancer
      specific mortality. Furthermore, we investigated interaction with prognostic and
      socioeconomic factors. Mortality Rate Ratios (MRR) were calculated in both
      unadjusted models, and adjusted for residential railway noise, lifestyle factors
      and socioeconomic variables. RESULTS: During a median of 7.3 years of follow-up,
      402 patients died; 274 from breast cancer. We found no association between time
      weighted averages of residential road traffic noise 1-, 3- or 5-years before
      death, or over the entire follow-up period, and overall or breast cancer-specific
      mortality. A 10dB higher road traffic noise from diagnosis until censoring was
      associated with an adjusted MRR of 0.94 (0.81-1.08) for all-cause mortality. The
      association was modified by lymph node involvement, with a MRR of 1.20 (0.97
      1.48) for those with tumor-positive lymph nodes and 0.76 (0.59-0.98) for those
      without. CONCLUSION: The present study suggests no association between
      residential road traffic noise and concurrent mortality. As it is the first study
      of its kind, with relatively limited power, further studies are warranted.

PMID- 27687724
TI  - Crystal Structure of the Acid Sphingomyelinase-like Phosphodiesterase SMPDL3B
      Provides Insights into Determinants of Substrate Specificity.
AB  - The enzyme acid sphingomyelinase-like phosphodiesterase 3B (SMPDL3B) was shown to
      act as a negative regulator of innate immune signaling, affecting cellular lipid
      composition and membrane fluidity. Furthermore, several reports identified this
      enzyme as an off target of the therapeutic antibody rituximab, with implications
      in kidney disorders. However, structural information for this protein is lacking.
      Here we present the high resolution crystal structure of murine SMPDL3B, which
      reveals a substrate binding site strikingly different from its paralogs. The
      active site is located in a narrow boot-shaped cavity. We identify a unique loop
      near the active site that appears to impose size constraints on incoming
      substrates. A structure in complex with phosphocholine indicates that the protein
      recognizes this head group via an aromatic box, a typical choline-binding motif.
      Although a potential substrate for SMPDL3B is sphingomyelin, we identify other
      possible substrates such as CDP-choline, ATP, and ADP. Functional experiments
      employing structure-guided mutagenesis in macrophages highlight amino acid
      residues potentially involved in recognition of endogenous substrates. Our study
      is an important step toward elucidating the specific function of this poorly
      characterized enzyme.

PMID- 27687725
TI  - Protein Phosphatase PP5 Controls Bone Mass and the Negative Effects of
      Rosiglitazone on Bone through Reciprocal Regulation of PPARgamma (Peroxisome
      Proliferator-activated Receptor gamma) and RUNX2 (Runt-related Transcription
      Factor 2).
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) and runt-related
      transcription factor 2 (RUNX2) are key regulators of mesenchymal stem cell (MSC)
      differentiation toward adipocytes and osteoblasts, respectively. Post
      translational modifications of these factors determine their activities.
      Dephosphorylation of PPARgamma at Ser-112 is required for its adipocytic
      activity, whereas phosphorylation of RUNX2 at serine 319 (Ser-319) promotes its
      osteoblastic activity. Here we show that protein phosphatase 5 (PP5) reciprocally
      regulates each receptor by targeting each serine. Mice deficient in PP5
      phosphatase have increased osteoblast numbers and high bone formation, which
      results in high bone mass in the appendicular and axial skeleton. This is
      associated with a substantial decrease in lipid-containing marrow adipocytes.
      Indeed, in the absence of PP5 the MSC lineage allocation is skewed toward
      osteoblasts and away from lipid accumulating adipocytes, although an increase in
      beige adipocyte gene expression is observed. In the presence of rosiglitazone,
      PP5 translocates to the nucleus, binds to PPARgamma and RUNX2, and
      dephosphorylates both factors, resulting in activation of PPARgamma adipocytic
      and suppression of RUNX2 osteoblastic activities. Moreover, shRNA knockdown of
      PP5 results in cells refractory to rosiglitazone treatment. Lastly, mice
      deficient in PP5 are resistant to the negative effects of rosiglitazone on bone,
      which in wild type animals causes a 50% decrease in trabecular bone mass. In
      conclusion, PP5 is a unique phosphatase reciprocally regulating PPARgamma and
      RUNX2 activities in marrow MSC.

PMID- 27687726
TI  - Psoralen and Ultraviolet A Light Treatment Directly Affects Phosphatidylinositol
      3-Kinase Signal Transduction by Altering Plasma Membrane Packing.
AB  - Psoralen and ultraviolet A light (PUVA) are used to kill pathogens in blood
      products and as a treatment of aberrant cell proliferation in dermatitis,
      cutaneous T-cell lymphoma, and graft-versus-host disease. DNA damage is well
      described, but the direct effects of PUVA on cell signal transduction are poorly
      understood. Because platelets are anucleate and contain archetypal signal
      transduction machinery, they are ideally suited to address this. Lipidomics on
      platelet membrane extracts showed that psoralen forms adducts with unsaturated
      carbon bonds of fatty acyls in all major phospholipid classes after PUVA. Such
      adducts increased lipid packing as measured by a blue shift of an environment
      sensitive fluorescent probe in model liposomes. Furthermore, the interaction of
      these liposomes with lipid order-sensitive proteins like amphipathic lipid
      packing sensor and alpha-synuclein was inhibited by PUVA. In platelets, PUVA
      caused poor membrane binding of Akt and Bruton's tyrosine kinase effectors
      following activation of the collagen glycoprotein VI and thrombin protease
      activated receptor (PAR) 1. This resulted in defective Akt phosphorylation
      despite unaltered phosphatidylinositol 3,4,5-trisphosphate levels. Downstream
      integrin activation was furthermore affected similarly by PUVA following PAR1
      (effective half-maximal concentration (EC50), 8.4 +/- 1.1 versus 4.3 +/- 1.1 MUm)
      and glycoprotein VI (EC50, 1.61 +/- 0.85 versus 0.26 +/- 0.21 MUg/ml) but not
      PAR4 (EC50, 50 +/- 1 versus 58 +/- 1 MUm) signal transduction. Our findings were
      confirmed in T-cells from graft-versus-host disease patients treated with
      extracorporeal photopheresis, a form of systemic PUVA. In conclusion, PUVA
      increases the order of lipid phases by covalent modification of phospholipids,
      thereby inhibiting membrane recruitment of effector kinases.

PMID- 27687727
TI  - Prohibitin 1 Regulates the H19-Igf2 Axis and Proliferation in Hepatocytes.
AB  - Prohibitin 1 (PHB1) is a mitochondrial chaperone that regulates cell growth. Phb1
      knock-out mice exhibit liver injury and hepatocellular carcinoma (HCC). Phb1
      knock-out livers show induction of tumor growth-associated genes, H19 and insulin
      like growth factor 2 (Igf2). These genes are controlled by the imprinting control
      region (ICR) containing CCCTC-binding transcription factor (CTCF)-binding sites.
      Because Phb1 knock-out mice exhibited induction of H19 and Igf2, we hypothesized
      that PHB1-mediated regulation of the H19-Igf2 axis might control cell
      proliferation in normal hepatocytes. H19 and Igf2 were induced (8-20-fold) in 3
      week-old Phb1 knock-out livers, in Phb1 siRNA-treated AML12 hepatocytes (2-fold),
      and HCC cell lines when compared with control. Phb1 knockdown lowered CTCF
      protein in AML12 by ~30% when compared with control. CTCF overexpression lowered
      basal H19 and Igf2 expression by 30% and suppressed Phb1 knockdown-mediated
      induction of these genes. CTCF and PHB1 co-immunoprecipitated and co-localized on
      the ICR element, and Phb1 knockdown lowered CTCF ICR binding activity. The
      results suggest that PHB1 and CTCF cooperation may control the H19-Igf2 axis.
      Human HCC tissues with high levels of H19 and IGF2 exhibited a 40-50% reduction
      in PHB1 and CTCF expression and their ICR binding activity. Silencing Phb1 or
      overexpressing H19 in the mouse HCC cell line, SAMe-D, induced cell growth.
      Blocking H19 induction prevented Phb1 knockdown-mediated growth, whereas H19
      overexpression had the reverse effect. Interestingly H19 silencing induced PHB1
      expression. Taken together, our results demonstrate that the H19-Igf2 axis is
      negatively regulated by CTCF-PHB1 cooperation and that H19 is involved in
      modulating the growth-suppressive effect of PHB1 in the liver.

PMID- 27687728
TI  - Alternative Selection of beta-Site APP-Cleaving Enzyme 1 (BACE1) Cleavage Sites
      in Amyloid beta-Protein Precursor (APP) Harboring Protective and Pathogenic
      Mutations within the Abeta Sequence.
AB  - beta-Site APP-cleaving enzyme 1 (BACE1) cleaves amyloid beta-protein precursor
      (APP) at the bond between Met671 and Asp672 (beta-site) to generate the carboxyl
      terminal fragment (CTFbeta/C99). BACE1 also cleaves APP at another bond between
      Thr681 and Gln682 (beta'-site), yielding CTFbeta'/C89. Cleavage of CTFbeta/C99 by
      gamma-secretase generates Abeta(1-XX), whereas cleavage of CTFbeta'/C89 generates
      Abeta(11-XX). Thus, beta'-site cleavage by BACE1 is amyloidolytic rather than
      amyloidogenic. beta' cleavage of mouse APP is more common than the corresponding
      cleavage of human APP. We found that the H684R substitution within human Abeta,
      which replaces the histidine in the human protein with the arginine found at the
      corresponding position in mouse, facilitated beta' cleavage irrespective of the
      species origin of BACE1, thereby significantly increasing the level of Abeta(11
      XX) and decreasing the level of Abeta(1-XX). Thus, amino acid substitutions
      within the Abeta sequence influenced the selectivity of alternative beta- or
      beta'-site cleavage of APP by BACE1. In familial Alzheimer's disease (FAD), the
      APP gene harbors pathogenic variations such as the Swedish (K670N/M671L), Leuven
      (E682K), and A673V mutations, all of which decrease Abeta(11-40) generation,
      whereas the protective Icelandic mutation (A673T) increases generation of
      Abeta(11-40). Thus, A673T promotes beta' cleavage of APP and protects subjects
      against AD. In addition, CTFbeta/C99 was cleaved by excess BACE1 activity to
      generate CTFbeta'/C89, followed by Abeta(11-40), even if APP harbored pathogenic
      mutations. The resultant Abeta(11-40) was more metabolically labile in vivo than
      Abeta(1-40). Our analysis suggests that some FAD mutations in APP are
      amyloidogenic and/or amyloidolytic via selection of alternative BACE1 cleavage
      sites.

PMID- 27687729
TI  - Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier (CHCHD4)
      Regulate p53 Protein Nuclear Activity in Response to Exercise.
AB  - Although exercise is linked with improved health, the specific molecular
      mechanisms underlying its various benefits require further clarification. Here we
      report that exercise increases the nuclear localization and activity of p53 by
      acutely down-regulating coiled-coil-helix-coiled-coil-helix domain 4 (CHCHD4), a
      carrier protein that mediates p53 import into the mitochondria. This response to
      exercise is lost in transgenic mice with constitutive expression of CHCHD4.
      Mechanistically, exercise-induced nuclear transcription factor FOXO3 binds to the
      CHCHD4 promoter and represses its expression, preventing the translocation of p53
      to the mitochondria and thereby increasing p53 nuclear localization. The
      synergistic increase in nuclear p53 and FOXO3 by exercise can facilitate their
      known interaction in transactivating Sirtuin 1 (SIRT1), a NAD+-dependent histone
      deacetylase that mediates adaptation to various stresses. Thus, our results
      reveal one mechanism by which exercise could be involved in preventing cancer and
      potentially other diseases associated with aging.

PMID- 27687731
TI  - Conjugative DNA-transfer in Streptomyces, a mycelial organism.
AB  - Conjugative DNA-transfer in the Gram-positive mycelial soil bacterium
      Streptomyces, well known for the production of numerous antibiotics, is a unique
      process involving the transfer of a double-stranded DNA molecule. Apparently it
      does not depend on a type IV secretion system but resembles the segregation of
      chromosomes during bacterial cell division. A single plasmid-encoded protein,
      TraB, directs the transfer from the plasmid-carrying donor to the recipient. TraB
      is a FtsK-like DNA-translocase, which recognizes a specific plasmid sequence,
      clt, via interaction with specific 8-bp repeats. Chromosomal markers are
      mobilized by the recognition of clt-like sequences randomly distributed all over
      the Streptomyces chromosomes. Fluorescence microcopy with conjugative reporter
      plasmids and differentially labelled recipient strains revealed conjugative
      plasmid transfer at the lateral walls of the hyphae, when getting in contact.
      Subsequently, the newly transferred plasmids cross septal cross walls, which
      occur at irregular distances in the mycelium and invade the neighboring
      compartments, thus efficiently colonizing the recipient mycelium. This
      intramycelial plasmid spreading requires the DNA-translocase TraB and a complex
      of several Spd proteins. Inactivation of a single spd gene interferes with
      intramycelial plasmid spreading. The molecular function of the Spd proteins is
      widely unknown. Spd proteins of different plasmids are highly diverse, none
      showing sequence similarity to a functionally characterized protein. The integral
      membrane protein SpdB2 binds DNA, peptidoglycan and forms membrane pores in vivo
      and in vitro. Intramycelial plasmid spreading is an adaptation to the mycelial
      growth characteristics of Streptomyces and ensures the rapid dissemination of the
      plasmid within the recipient colony before the onset of sporulation.

PMID- 27687730
TI  - Neuropilin 2 Signaling Is Involved in Cell Positioning of Adult-born Neurons
      through Glycogen Synthase Kinase-3beta (GSK3beta).
AB  - Proper positioning of neurons is fundamental for brain functions. However, little
      is known on how adult-born neurons generated in the hilar side of hippocampal
      dentate gyrus migrate into the granular cell layer. Because class 3 Semaphorins
      (Sema3) are involved in dendritic growth of these newborn neurons, we examined
      whether they are essential for cell positioning. We disrupted Sema3 signaling by
      silencing neuropilin 1 (NRP1) or 2 (NRP2), the main receptors for Sema3A and
      Sema3F, in neural progenitors of adult mouse dentate gyrus. Silencing of NRP2,
      but not NRP1, affected cell positioning of adult newborn neurons. Glycogen
      synthase kinase-3beta (GSK3beta) knockdown phenocopied this NRP2 silencing
      mediated cell positioning defect, but did not affect dendritic growth.
      Furthermore, GSK3beta is activated upon stimulation with Sema3F, and GSK3beta
      overexpression rescued the cell positioning phenotypes seen in NRP2-deficient
      neurons. These results point to a new role for NRP2 in the positioning of neurons
      during adult hippocampal neurogenesis, acting via the GSK3beta signaling pathway.

PMID- 27687732
TI  - Late-Onset Friedreich's Ataxia (LOFA) Mimicking Charcot-Marie-Tooth Disease Type
      2: What Is Similar and What Is Different?
AB  - Herein, we report a patient that presented with late-onset progressive steppage
      gait, neuropathy and pes cavus, suggesting Charcot-Marie-Tooth (CMT) disease.
      Subsequent genetic investigation confirmed Friedreich's ataxia (FRDA). We
      demonstrate that late-onset Friedreich's ataxia (LOFA) may be a CMT mimicker.
      This case reinforces that other genetic conditions may clinically resemble CMT.
      The clinical similarities between CMT and FRDA include a symmetrical neuropathy
      (axonal in FRDA), steppage gait, and eventually scoliosis. We suggest that late
      onset forms of hereditary neuropathies should be carefully evaluated, since LOFA
      may be a CMT mimicker.

PMID- 27687733
TI  - Dominant factor analysis of B-flow twinkling sign with phantom and simulation
      data.
AB  - BACKGROUND AND PURPOSE: The twinkling sign in B-flow imaging (BFI-TS) has been
      reported in the literature to increase both specificity and sensitivity compared
      to the traditional gray-scale imaging. Unfortunately, there has been no
      conclusive study on the mechanism of this effect. METHODS: In the study presented
      here, a comparative test on phantoms is introduced, where the variance of a phase
      estimator is used to quantify the motion amplitude. The statistical inference is
      employed later to find the dominate factor for the twinkling sign, which is
      proven by computer simulation. RESULTS: Through the analysis, it is confirmed
      that the tissue viscoelasticity is closely coupled with the twinkling sign.
      Moreover, the acoustic radiation force caused by tissue attenuation is found to
      be the trigger of the twinkling sign. CONCLUSION: Based on these findings, the
      BFI-TS is interpreted as a tissue movement triggering vibration of
      microcalcifications particle.

PMID- 27687734
TI  - Sonoreperfusion Therapy Kinetics in Whole Blood Using Ultrasound, Microbubbles
      and Tissue Plasminogen Activator.
AB  - Coronary intervention for myocardial infarction often results in microvascular
      embolization of thrombus. Sonoreperfusion therapy (SRP) using ultrasound and
      microbubbles restored perfusion in our in vitro flow model of microvascular
      obstruction. In this study, we assessed SRP efficacy using whole blood as the
      perfusate with and without tissue plasminogen activator (tPA). In a phantom
      vessel bearing a 40-MUm-pore mesh to simulate the microvasculature, microthrombi
      were injected to cause microvascular obstruction and were treated using SRP.
      Without tPA, the lytic rate increased from 2.6 +/- 1.5 mmHg/min with 1000-cycle
      pulses to 7.3 +/- 3.2 mmHg/min with 5000-cycle ultrasound pulses (p < 0.01). The
      lytic index was similar for tPA-only ([2.0 +/- 0.5] * 10-3 mmHg-1 min-1) and 5000
      cycles without tPA ([2.3 +/- 0.5] * 10-3 mmHg-1 min-1) (p = 0.5) but increased
      ([3.6 +/- 0.8] * 10-3 mmHg-1 min-1) with tPA in conjunction with 5000-cycles
      ultrasound (p < 0.01). In conclusion, SRP restored microvascular perfusion in
      whole blood, SRP lytic rate in experiments without tPA increased with ultrasound
      pulse length and efficacy increased with the addition of tPA.

PMID- 27687736
TI  - The Case Report of Priapus and a Modern Approach to an Ancient Affliction.
AB  - INTRODUCTION: Priapism, taking its name from God Priapus, is total or partial
      erection lasting longer than 4 hours independent of sexual stimulus and can
      result in erectile dysfunction. There are three subtypes of priapism. AIM: To
      review the three subtypes of priapism, their pathophysiology, current treatment
      options, and complications. METHODS: The literature including priapism
      guidelines, review articles, and current trial studies was reviewed and the
      priapism type of God Priapus was investigated according to the mythology. MAIN
      OUTCOME MEASURES: All three types of priapism were reviewed for etiology,
      diagnosis, and management. Medical and surgical treatment options were reviewed
      in relation to the current literature. Special emphasis concerned current
      treatment strategies and controversial surgical topics. RESULTS: Ischemic
      priapism is the most common type, constituting 95% of all cases, and is an
      emergency. First-line treatments are blood aspiration and intracavernosal
      sympathomimetic drug injections. If these fail, then surgical shunt operations
      are recommended. A T-shunt combined with corporal tunneling is the currently
      popular option. Immediate penile prosthesis implantation is recommended for
      patients who present 48 to 72 hours after the onset of a priapism episode. High
      flow priapism is caused by irregular arterial cavernosal blood flow, which
      usually occurs after a blunt perineal trauma. Antiandrogens and selective
      arterial embolization are the treatment options. Stuttering priapism is
      repetitive, self-limiting ischemic priapism and frequent in patients with sickle
      cell anemia. Ketoconazole is safe, cheap, and effective and appears to be a
      logical and suitable current treatment option to prevent further episodes, which
      is the primary treatment goal of stuttering priapism. CONCLUSION: Priapism is a
      relatively common condition but not well known by clinicians. The lack and delay
      of treatment result in irreversible complications such as erectile dysfunction.
      Each type of priapism should be diagnosed and treated correctly with caution.

PMID- 27687735
TI  - CellMapper: rapid and accurate inference of gene expression in difficult-to
      isolate cell types.
AB  - We present a sensitive approach to predict genes expressed selectively in
      specific cell types, by searching publicly available expression data for genes
      with a similar expression profile to known cell-specific markers. Our method,
      CellMapper, strongly outperforms previous computational algorithms to predict
      cell type-specific expression, especially for rare and difficult-to-isolate cell
      types. Furthermore, CellMapper makes accurate predictions for human brain cell
      types that have never been isolated, and can be rapidly applied to diverse cell
      types from many tissues. We demonstrate a clinically relevant application to
      prioritize candidate genes in disease susceptibility loci identified by GWAS.

PMID- 27687737
TI  - Nutritional risk factors and status of serum 25(OH)D levels in patients with
      breast cancer: A case control study in India.
AB  - To study the nutritional risk factors and status of serum 25(OH)D levels in
      patients with breast cancer. A total of 100 women (cases) with confirmed breast
      cancer (BC) matched with equal number of healthy females (controls) of similar
      age and socioeconomic status (SES) were included in study. Controls included were
      nonbreast cancer patients who accompanied the patients to a tertiary care
      hospital. All the subjects (cases and controls) were administered a
      questionnaires to collect data on socioeconomic status, dietary pattern and the
      frequency of food consumption using a validated food frequency questionnaire.
      Anthropometric assessment was done for waist and hip circumference to calculate
      waist to hip ratio (WHR). Non fasting blood samples were collected for serum 25
      hydroxyvitamin D [25(OH)D] levels estimation using chemiluminescent immunoassay
      technique and total serum calcium levels by colorimetric assay technique. Serum
      25(OH)D and total calcium levels were expressed in ng/ml and mg/dl. Vitamin D
      deficiency was defined as per the guidelines set by United States Endocrine
      Society. The mean age of cases and controls was 45+/-9 and 46+/-10 years
      respectively. On multivariate analysis, an inverse association with BC was found
      for less frequency of fruits consumption with an adjusted (ORs, 95% CI) (2.7, 0.5
      15.7) respectively. Mushroom intake was inversely associated with risk of BC
      (ORs, 95% CI) (5.6, 1.9-16.6). Saturated fat intake and high WHR were
      significantly associated with high risk of BC with adjusted ORs, 95% CI of (3.4,
      1.4-8.1) and (5, 1.4-17). A significant association (p<0.05) was found between
      low serum 25(OH)D levels and the risk of BC with adjusted ORs, 95% CI of (2.5,
      0.9-7.4). Majority of the patients with BC were suffering from vitamin D
      deficiency. Dietary intake of mushrooms containing vitamin D naturally was found
      to be associated with decreased risk of breast cancer. A significant association
      was found between low serum 25(OH)D levels (<20ng/ml) with the risk of BC.
      Obesity as a consequence of nutritional risk factors determined by higher WHR was
      found to be significantly associated with the risk of BC.

PMID- 27687738
TI  - Serum 25-hydroxyvitamin D concentration is not associated with glomerular
      filtration rate in a predominantly obese otherwise healthy population.
AB  - Evidence from observational studies indicates a role for vitamin D in kidney
      function and progression to chronic kidney disease. Findings from animal studies
      have proposed underlying mechanisms including increased activation of the renin
      angiotensin system, increased blood pressure, insulin resistance and chronic low
      grade inflammation. However, human studies are limited by confounders arising
      from heterogeneous samples of participants. We examined the relationship between
      25(OH)D and estimated glomerular filtration rate (eGFR) in a predominantly obese
      otherwise healthy and drug-naive population with no history of chronic kidney
      disease (CKD). One hundred and twenty one non-diabetic (75g oral glucose
      tolerance test; OGTT) volunteers (70 males and 51 females), aged 18-57 years
      participated in the study. Median 25(OH)D level was 37nmol/L with no difference
      by sex. Twenty six participants (21.5%) had 25(OH)D <25 nmol/L, 75 participants
      (62%) had 25(OH)D of 25-49.99nmol/L, and 20 participants (16.5%) had 25(OH)D
      >=50nmol/L. In univariate analysis, 25(OH)D was related negatively to percent
      body fat and 2-h glucose level post OGTT. Mean (SD) eGFR was 113.1
      (14.9)mL/min/1.73m2, and in the multivariable analysis, it was related to age,
      sex, percent body fat and 2-h glucose level post OGTT, but not to 25(OH)D.
      Furthermore, there was no relationship between eGFR and 25(OH)D across BMI
      categories. Our data suggest that measuring 25(OH)D in predominantly obese
      otherwise healthy individuals with no history of CKD may not be beneficial in
      early recognition of kidney disease.

PMID- 27687739
TI  - Electroencephalographic coupling in the amygdala and prefrontal cortex in
      relation to the estrous cycle and duration of vaginocervical stimulation in the
      rat.
AB  - The influence of the duration of vaginocervical stimulation (VCS) on the
      electroencephalographic activity (EEG) of medial amygdala (MeA) and prefrontal
      cortex (PFC) in rats during proestrus-estrus (P-E) and diestrus (D) was examined.
      Using a glass syringe plunger, a constant force of 300g was exerted against the
      cervix during 60s. Relative power (RP) and correlation of three EEG band
      frequencies were compared between the first and last 30s intervals of VCS. A
      higher RP of the 4-7Hz band and a lower RP of the fast frequencies were observed
      in the MeA and PFC in P-E females during the first 30s of VCS as compared to the
      last 30s. Only during P-E, a higher interamygdaline correlation in the 8-12Hz
      band and a lower correlation in the 13-21Hz band during the first 30s were
      observed. Similarly, a higher interamygdaline correlation in the 8-12Hz band was
      observed during the first 30s of VCS during P-E as compared to D. During the last
      30s of VCS there was no difference between phases. The VCS evoked EEG changes in
      the MeA that varied between phases of the estrous cycle and depended on the
      duration of the stimulation. These effects could be associated with the
      quantification processes of VCS that has been proposed to occur in the amygdala.
      These findings show differential responsiveness of the MeA and PFC according to
      the amount of VCS received, and that the response varies according to the estrous
      cycle.

PMID- 27687740
TI  - Opposite effects of acute and chronic amphetamine on Nurr1 and NF-kappaB p65 in
      the rat ventral tegmental area.
AB  - Dopamine neurons are overstimulated by drugs of abuse and suffer molecular
      alterations that lead to addiction behavior. Nurr1 is a transcription factor
      crucial for dopamine neurons survival and dopamine production, activating the
      transcription of key genes like tyrosine hydroxylase (TH). Interestingly, nuclear
      factor-kappa B (NF-kappaB) has emerged as a new Nurr1 partner in response to
      inflammatory stimulus. In this study we evaluated the effects of single and
      repeated amphetamine administration in the expression of Nurr1 and the NF-kappaB
      p65 subunit in the rat ventral tegmental area (VTA). We found that acute
      amphetamine treatment increased Nurr1, p65 and TH protein levels in the VTA. On
      the other hand, chronic amphetamine treatment decreased Nurr1 and p65 protein
      levels, but TH was unchanged. Mammalian reporter assays in cell lines showed that
      p65 represses Nurr1 transcriptional activity in an artificial promoter driven by
      Nurr1 response elements and in the native rat TH promoter. These results indicate
      that Nurr1 and NF-kappaB p65 factors are involved in the adaptive response of
      dopamine neurons to psychostimulants and that both transcription factors could be
      regulating Nurr1-dependent transactivation in the VTA.

PMID- 27687741
TI  - Treatment outcomes of endoscopic resection for rectal carcinoid tumors: an
      analysis of the resectability and long-term results from 46 consecutive cases.
AB  - AIM: In Japan, most of colorectal carcinoid tumors developed in rectum. The
      choice of treatment is important because surgical treatment may need to construct
      artificial anus. Although curative endoscopic resection (ER) is desirable from
      the point of quality of life, sufficient evidence of endoscopic treatment for
      rectal carcinoid tumors is not fully obtained. METHODS: Between April 2001 and
      August 2013, 46 rectal carcinoid tumors in 46 patients who underwent either with
      endoscopic mucosal resection with a ligation device (EMR-L) or endoscopic
      submucosal dissection (ESD) were analyzed retrospectively. The rates of en bloc
      resection, positive for lateral and/or vertical margin, curative resection, local
      recurrence, additional treatments, overall and disease-specific survival rate
      after ER were evaluated during follow-up (median observation period 61.6 months).
      RESULTS: Twenty-two lesions were treated by EMR-L and 24 lesions were treated by
      ESD. Both groups had similar mean tumor size (EMR-L: 6.2 mm, ESD: 6.0 mm). The
      rate of en bloc resection, negative for both lateral and vertical margins, and
      curative resection were, respectively, 73%, 63%, and 50% for EMR-L, 100%, 100%,
      and 83% for ESD. These results suggested that the rate of resectability and
      curability for ESD was significantly higher than EMR-L (p < 0.05). Complications
      such as perforation and bleeding did not occur in both groups. Fifteen patients
      were judged as non-curative and 3 patients underwent additional surgery and lymph
      node metastasis was evident in 1 patient. Remained 11 patients were carefully
      followed-up, and so far no obvious recurrence was found. Thirty-two patients
      (84%) were eligible for long-term follow-up and 5-year overall and disease
      specific survival rates were 100% and 100%, respectively. CONCLUSION: The long
      term outcomes of ER for rectal carcinoid tumors were excellent. ESD has advantage
      for resectability and curability compared with EMR-L; therefore, ESD is more
      favorable procedure as treatment for rectal carcinoid tumors.

PMID- 27687742
TI  - The effects of intermittent calorie restriction on metabolic health: Rationale
      and study design of the HELENA Trial.
AB  - Mechanistic studies suggest benefits of intermittent calorie restriction (ICR) in
      chronic disease prevention that may exceed those of continuous calorie
      restriction (CCR), even at equal net calorie intake. Despite promising results
      from first trials, it remains largely unknown whether ICR-induced metabolic
      alterations reported from experimental studies can also be observed in humans,
      and whether ICR diets are practicable and effective in real life situations.
      Thus, we initiated the HELENA Trial to test the effects of ICR (eu-caloric diet
      on five days and very low energy intake on two days per week) on metabolic
      parameters and body composition over one year. We will assess the effectiveness
      of ICR compared to CCR and a control diet over a 12-week intervention, 12-week
      maintenance phase and 24-week follow-up in 150 overweight or obese non-smoking
      adults (50 per group, 50% women). Our primary endpoint is the difference between
      ICR and CCR with respect to fold-changes in expression levels of 82 candidate
      genes in abdominal subcutaneous adipose tissue biopsies (SATb) during the
      intervention phase. The candidate genes represent pathways, which may link
      obesity-related metabolic alterations with the risk for major chronic diseases.
      In secondary and exploratory analyses, changes in metabolic, hormonal,
      inflammatory and metagenomic parameters measured in different biospecimens (SATb,
      blood, urine, stool) are investigated and effects of ICR/CCR/control on imaging
      based measures of subcutaneous, visceral and hepatic fat are evaluated. Our study
      is the first randomized trial over one year testing the effects of ICR on
      metabolism, body composition and psychosocial factors in humans.

PMID- 27687744
TI  - Development of a predictive model for urgency urinary incontinence.
AB  - The ability to set realistic expectations of treatment response in patients with
      overactive bladder (OAB) can have an impact on patient engagement and adherence
      to study medication. In order to help set treatment expectations for OAB, a
      Physician Predictive Tool has been developed based on predictive modelling.
      Models have been developed utilizing data from eight Phase 3 and 4 fesoterodine
      clinical trials and these models enable the prediction of individual treatment
      response in subjects with OAB, based on various baseline characteristics. The
      data utilized and covariates that were hypothesized to influence treatment
      response are described. The model selection and development process are also
      outlined, and the final model and some example results utilizing this model are
      presented. Finally, we discuss the potential benefits and limitations of such a
      predictive tool.

PMID- 27687745
TI  - Exploring the Relationship Between Online Social Network Site Usage and the
      Impact on Quality of Life for Older and Younger Users: An Interaction Analysis.
AB  - BACKGROUND: Analyzing content generated by users of social network sites has been
      shown to be beneficial across a number of disciplines. Such analysis has revealed
      the precise behavior of users that details their distinct patterns of engagement.
      An issue is evident whereby without direct engagement with end users, the
      reasoning for anomalies can only be the subject of conjecture. Furthermore, the
      impact of engaging in social network sites on quality of life is an area which
      has received little attention. Of particular interest is the impact of online
      social networking on older users, which is a demographic that is specifically
      vulnerable to social isolation. A review of the literature reveals a lack of
      knowledge concerning the impact of these technologies on such users and even less
      is known regarding how this impact varies across different demographics.
      OBJECTIVE: The objective of our study was to analyze user interactions and to
      survey the attitudes of social network users directly, capturing data in four key
      areas: (1) functional usage, (2) behavioral patterns, (3) technology, and (4)
      quality of life. METHODS: An online survey was constructed, comprising 32
      questions. Each question directly related to a research question. Respondents
      were recruited through a variety of methods including email campaigns, Facebook
      advertisements, and promotion from related organizations. RESULTS: In total, data
      was collected from 919 users containing 446 younger and 473 older users. In
      comparison to younger users, a greater proportion of older users (289/473, 61.1%
      older vs 218/446, 48.9% younger) (P<.001) stated that Facebook had either a
      positive or huge impact on their quality of life. Furthermore, a greater
      percentage of older users strongly agreed that Facebook strengthened their
      relationship with other people (64/473, 13.5% older vs 40/446, 9.0%younger)
      (P=.02). In comparison to younger users, a greater proportion of older users had
      more positive emotions-classified as slightly better or very good-during their
      engagement with Facebook (186/473, 39.3% older vs 120/446, 26.9% younger)
      (P<.001). CONCLUSIONS: The results reveal that despite engaging at considerably
      lower rates with significantly fewer connections, older users gain a greater
      quality-of-life benefit. Results disclose how both cohorts vary in their use,
      interactions, and rationale for engaging with Facebook.

PMID- 27687743
TI  - Ethical and clinical safety considerations in the design of an effectiveness
      trial: A comparison of buprenorphine versus naltrexone treatment for opioid
      dependence.
AB  - We examine ethical challenges encountered in the design of an effectiveness trial
      (CTN-0051; X:BOT), comparing sublingual buprenorphine-naloxone (BUP-NX), an
      established treatment for opioid dependence, to the newer extended-release
      injectable naltrexone (XR-NTX). Ethical issues surrounded: 1) known poor
      effectiveness of one possible, commonly used treatment as usual control condition
      detoxification followed by counseling without medication; 2) the role of
      patients' preferences for treatments, given that treatments were clinically
      approved and available to the population; 3) differences between the optimal
      "usual treatment" clinical settings for different treatments making it
      challenging to design a fair comparison; 4) vested interest groups favoring
      different treatments exerting potential influence on the design process; 5)
      potentially vulnerable populations of substance users and prisoners; 6) potential
      therapeutic misconception in the implementation of safety procedures; and 7) high
      cost of a large trial limiting questions that could be addressed. We examine how
      the design features underlying these ethical issues are characteristic of
      effectiveness trials, which are often large trials that compare treatments with
      varying degrees of existing effectiveness data and familiarity to patients and
      clinicians, in community-based treatment settings, with minimal exclusion
      criteria that could involve vulnerable populations. Hence, investigators
      designing effectiveness trials may wish to remain alert to the possibility of
      similar ethical issues.

PMID- 27687746
TI  - Unresectability during open surgical exploration in planned cytoreductive surgery
      and hyperthermic intraperitoneal chemotherapy.
AB  - BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      are the treatment of choice for selected patients with peritoneal metastasis.
      Despite a stringent selection process, some patients were found to be
      unresectable only at surgery, which leads to disappointment and poor utilisation
      of limited infrastructural resources. This study aims to determine the pre
      operative factors associated with unresectability in planned CRS and HIPEC.
      METHODS: Retrospective analysis of 172 consecutive patients eligible for CRS and
      HIPEC at the National Cancer Centre Singapore from April 2004 to May 2014 was
      performed. Pre-operative factors (clinical presentation, disease factors, and
      investigation findings) between the unresectable (13%) and the successful groups
      (87%) were compared. RESULTS: Patient demographics between the two cohorts were
      comparable. In terms of clinical presentation, the unresectable group was more
      likely to present with bloating (p = .00), altered bowel habits (p = .04),
      abdominal distension (p = .00), palpable abdominal masses (p = .00) and palpable
      pouch of Douglas nodules (p = .00). Differences were also noted in disease
      factors with the unresectable group having more high-grade tumours (p = .01),
      inadequate initial resections (p = .01), progression through chemotherapy (p =
      .00) and shorter median disease-free intervals (p = .03). In addition,
      investigations in the unresectable group revealed more patients with elevated
      tumour markers (p = .01), thrombocytosis (p = .00) and computed tomography
      findings of ascites (p = .00), omental thickening (p = .00), lymphadenopathy (p =
      .02) and small bowel disease (p = .00). CONCLUSIONS: Significant factors
      associated with unresectability that were identified in our study could
      potentially create a new treatment algorithm and refine current selection process
      to exclude patients at risk of unresectability in planned CRS and HIPEC.

PMID- 27687747
TI  - "Multiparametric" and Other Words of Self-aggrandization.

PMID- 27687748
TI  - Use of Twitter Polls to Determine Public Opinion Regarding Content Presented at a
      Major National Specialty Society Meeting.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of using Twitter
      polls to assess public opinion regarding session content at a national specialty
      society meeting. METHODS: Twitter polls allow users to embed multiple-choice
      questions within tweets and automatically aggregate responses. Two radiologists
      attending the 2016 annual meeting of the ACR posted a Twitter poll containing the
      hashtag #ACR2016 during 10 meeting sessions addressing socioeconomics/advocacy,
      patient experience, and social media/informatics (20 polls total). Each poll
      contained a question asking for an opinion regarding the session's content. Polls
      were open for responses for 24 hours. RESULTS: The average number of responses
      per poll was significantly higher for the user with the larger number of Twitter
      followers (24.3 +/- 14.4 versus 11.2 +/- 9.8, P = .015). A total of 57% of
      respondents agreed that radiologists' payments should shift to value-based
      payments, and 86% agreed that radiologists should routinely survey their patients
      to monitor quality; however, 83% disagreed with basing physician payments on
      patient satisfaction scores. A total of 85% disagreed that the artificial
      intelligence supercomputer Watson will entirely replace radiologists. A total of
      76% agreed that social media can drive business at less cost than standard
      marketing. A total of 56% agreed with the direction of the ACR's advocacy and
      regulatory efforts, whereas 74% considered the ACR's advocacy efforts to be
      moderately or very useful for their practice. A total of 50% planned to change
      their practice on the basis of keynote remarks by Dr Ezekiel Emanuel.
      CONCLUSIONS: Twitter polls provide a free and easy infrastructure to potentially
      capture global public sentiment during the course of a medical society meeting.
      Their use may enrich and promote discussions of key session content.

PMID- 27687749
TI  - The Economic and Social Value of an Image Exchange Network: A Case for the Cloud.
AB  - As the health care environment continually changes, radiologists look to the
      ACR's Imaging 3.0(r) initiative to guide the search for value. By leveraging new
      technology, a cloud-based image exchange network could provide secure universal
      access to prior images, which were previously siloed, to facilitate accurate
      interpretation, improved outcomes, and reduced costs. The breast imaging
      department represents a viable starting point given the robust data supporting
      the benefit of access to prior imaging studies, existing infrastructure for image
      sharing, and the current workflow reliance on prior images. This concept is
      scalable not only to the remainder of the radiology department but also to the
      broader medical record.

PMID- 27687750
TI  - Quality Improvement of Breast MRI Reports With Standardized Templates for
      Structured Reporting.

PMID- 27687751
TI  - Partnering With Your Health System to Select and Implement Clinical Decision
      Support for Imaging.
AB  - Recent legislation mandates the documentation of appropriateness criteria
      consultation when ordering advanced imaging for Medicare patients to remain
      eligible for reimbursement. Implementation of imaging clinical decision support
      (CDS) is a solution adopted by many systems to automate compliance with the new
      requirements. This article is intended to help radiologists who are employed by,
      contracted with, or otherwise affiliated with systems planning to implement CDS
      in the near future and ensure that they are able to understand and contribute to
      the process wherever possible. It includes an in-depth discussion of the
      legislation, evidence for and against the efficacy of imaging CDS, considerations
      for selecting a CDS vendor, tips for configuring CDS in a fashion consistent with
      departmental goals, and pointers for implementation and change management.

PMID- 27687752
TI  - What Do Women Know About Breast Density? Results From a Population Survey of
      Virginia Women.
AB  - PURPOSE: Breast density reduces the sensitivity of mammography and is a moderate
      independent risk factor for breast cancer. Virginia is one of 24 states that
      currently require notification of patients when they have dense breasts. However,
      little is known about what women in the general population know about breast
      density. This survey study assessed knowledge about breast density and about its
      impact on mammography and breast cancer risk. METHODS: A random sample of 1024
      Virginia women between ages 35 and 70 years without breast cancer, reached by
      landline and cell phone, who completed a 24-minute interview. Bivariate and
      multivariate analysis was performed. RESULTS: Thirty-six percent of respondents
      had been informed about their breast density. These women were more likely to be
      familiar with the term "breast density." Seventy-five percent of respondents
      reported being either somewhat or very familiar with risk factors for breast
      cancer, but <1% spontaneously listed breast density as a risk factor. About half
      of women who had a mammogram in the last year were aware of their breast density.
      Overall, only one in five women were aware that density reduces the sensitivity
      of mammography and only one in eight were aware that density increases breast
      cancer risk. Very few respondents (5.3%) were able to correctly answer three
      density knowledge questions. Lower-education, African-American, and Jewish women
      were less knowledgeable about breast density. CONCLUSIONS: Although women are
      becoming aware of the term "breast density," they may not understand its
      relationship to cancer detection on mammography and, especially, its relationship
      to breast cancer risk.

PMID- 27687753
TI  - Telehealth monitor to measure physical activity and pressure relief maneuver
      performance in wheelchair users.
AB  - This study demonstrated the feasibility of a device for monitoring pressure
      relief maneuvers and physical activity for wheelchair users. The device counts
      the number of wheel pushes based on wheelchair acceleration and measures pressure
      relief maneuvers using a seat sensor consisting of three force sensing resistors
      (FSRs). To establish the feasibility of the seat sensor for the detection of
      pressure relief maneuvers, 10 wheelchair users and 10 non-disabled controls
      completed a series of wheelchair depression raises, forward trunk leans, and
      lateral trunk leans. The seat sensor was placed underneath the user's seat
      cushion. To establish the feasibility of wheel push counting, 10 full-time
      wheelchair users navigated a flat 50-m outdoor track and a 100-m outdoor obstacle
      course during self-propulsion (e.g., wheel pushes) and during assisted-propulsion
      (e.g., no wheel pushes). Of the 240 performed pressure relief, 225 were properly
      classified by the seat sensor (accuracy: 94%, sensitivity: 96%, specificity:
      80%). Sensitivity was highest for depression raises (98%) and lowest for front
      lean maneuvers (80%). The wheelchair activity monitor measured 2,112 pushes
      during the self-propulsion trials compared to 2,162 pushes measured with the
      instrumented push-rim (97.7%). During assisted-propulsion trials, there were 477
      incorrectly identified pushes (8.0 per trial).

PMID- 27687754
TI  - Studies on chemical constituents and anti-hepatoma effects of essential oil from
      Annona squamosa L. pericarps.
AB  - Annona squamosa L. fruit played great anti-neoplastic activities. Its pericarps
      were discarded as waste. In this study, essential oil extracted from A. squamosa
      L. pericarps (APEO) was obtained by hydrodistillation and analysed by GC-MS.
      Furthermore, the anti-hepatoma activities and the underlying mechanism of the oil
      were firstly described. A total of 59 compounds were identified by Gas
      chromatography-mass spectrometry (GC-MS). The major compound in the oil was (-)
      spathulenol (32.51%). The APEO demonstrated anti-hepatoma activity against SMMC
      7721 hepatoma cell line with IC50 lower than 55 MUg/mL. At the same time, nucleus
      shrinkage or broken were found in cells incubated with APEO through fluorescent
      microscope. In addition, pro-apoptosis and cell cycle arrest effects were
      confirmed by flow cytometry analysis.

PMID- 27687756
TI  - Erratum to: Perfluoroalkyl acids in aqueous samples from Germany and Kenya.

PMID- 27687757
TI  - Comparative effects of direct-fed microbials alone or with a trace minerals
      supplements on the productive performance, blood metabolites, and antioxidant
      status in grazing Awassi lambs.
AB  - Twenty Awassi lambs were used to find the effects of direct-fed microbials (DFM)
      and long-acting trace minerals rumen bolus (TMB) supplements on performance,
      blood biochemical variables, and antioxidant status of the lambs under grazing
      conditions. The lambs were randomly distributed into four groups as follows: (1)
      untreated, (2) oral dose of 5 mL DFM, (3) TMB, or (4) oral dose of 5 mL DFM and
      TMB. The treatments were carried out for 90 days. Supplementation with TMB
      significantly increased (P < 0.05) average daily gain (ADG) and feed efficiency
      compared with the control. A significant (P < 0.05) increase in blood albumin in
      the DFM and a significant (P < 0.05) decrease in aspartate aminotrasferase were
      found in the lambs supplemented with TMB alone or in combination with DFM.
      Supplementing lambs with TMB resulted in higher glutathione peroxidase, total
      antioxidant capacity (P < 0.001) and activity of superoxide dismutase (P < 0.05)
      compared with no supplementation and supplementation with DFM only. In
      conclusion, TMB supplementation had a positive impact on performance traits and
      the antioxidant system of the lambs under grazing condition.

PMID- 27687755
TI  - Aspergillosis and stem cell transplantation: An overview of experimental
      pathogenesis studies.
AB  - Invasive aspergillosis is a life-threatening infection caused by the
      opportunistic filamentous fungus Aspergillus fumigatus. Patients undergoing
      haematopoietic stem cell transplant (HSCT) for the treatment of hematological
      malignancy are at particularly high risk of developing this fatal infection. The
      susceptibility of HSCT patients to infection with A. fumigatus is a consequence
      of a complex interplay of both fungal and host factors. Here we review our
      understanding of the host-pathogen interactions underlying the susceptibility of
      the immunocompromised host to infection with A. fumigatus with a focus on the
      experimental validation of fungal and host factors relevant to HSCT patients.
      These include fungal factors such as secondary metabolites, cell wall
      constituents, and metabolic adaptations that facilitate immune evasion and
      survival within the host microenvironment, as well as the innate and adaptive
      immune responses involved in host defense against A. fumigatus.

PMID- 27687758
TI  - Erythrocyte micronucleus cytome assay of 17 wild bird species from the central
      Monte desert, Argentina.
AB  - Birds have the potential to be considered valuable bioindicators of the quality
      of ecosystems and the environmental impact of pollutants. The aims of this study
      were to determine the micronuclei frequency and other nuclear abnormalities in
      erythrocytes by analyzing a wild bird community from central Monte desert
      (Argentina) and to clarify if there were any differences among certain species.
      Frequencies of nuclear abnormalities were determined in 73 wild birds belonging
      to 17 species and two orders (Passeriformes and Columbiformes). A high proportion
      of individuals, 90.4 and 80.9 %, had erythrocytes with micronuclei and nuclear
      buds, respectively. Notched nuclei, binucleated cells, nuclear tails, and
      nucleoplasmic bridges were also recorded. Certain species appeared to be more
      informative than others with regard to the possibility of being used as
      bioindicators of genetic damage. Saltator aurantiirostris and Columbina picui
      were the only species that showed significantly different frequencies of nuclear
      alterations, in comparison with the other species. The frequencies here presented
      are the first reported for these bird species from the orders Passeriformes and
      Columbiformes. This research supports the notion that the use of these biomarkers
      could be effectively applied to evaluate spontaneous or induced genetic
      instability in wild birds.

PMID- 27687759
TI  - Sorption of selected pharmaceuticals and pesticides on different river sediments.
AB  - In the present work, the sorption ability of 17 pharmaceutical compounds, two
      metabolites, and 15 pesticides (34 target compounds in total) onto four different
      river sediments was investigated separately. Selected compounds present the most
      frequently prescribed pharmaceuticals in human and animal medicine and the most
      frequently used pesticides in agriculture. Their presence into the surface,
      ground, and waste waters was confirmed into the numerous papers in literature, as
      well as their presence into the river sediments (for some of them). However,
      investigations of their sorption onto the river sediments, as major natural
      protection from potential pollution of ground water by them is missing. Sorption
      in this study was investigated onto river sediments taken from rivers in the
      Republic of Serbia, where only less than 10 % of total generated waste water
      passes through mainly basic treatment processes. Experiments were based on batch
      equilibrium procedures and obtained solutions were analyzed by previously
      developed and validated sensitive high performance liquid chromatography-tandem
      mass spectrometry (HPLC-MS/MS) analytical methods. All results were modeled by
      Freundlich isotherms. Obtained results have shown that Kf coefficient values are
      in correlation with organic carbon content. Kd sorption coefficient values were
      relatively low and ranged in wide ranges for almost all compounds and sediments.
      That implicates on the conclusion that capacities of the investigated sorbents
      are not large for those compounds.

PMID- 27687760
TI  - Organophosphate pesticide in agricultural soils from the Yangtze River Delta of
      China: concentration, distribution, and risk assessment.
AB  - Organophosphorus pesticides (OPPs) are used worldwide and pose great risks to
      human health. However, information on their presence in agricultural soils at
      regional scale and the associated risks is limited. In this study, an extensive
      investigation on agricultural soils was conducted throughout the Yangtze River
      Delta (YRD) of China to reveal the status of OPP pollution. The total
      concentrations of the nine OPPs ranged from <3.0 to 521 ng g-1 dry weight, with a
      mean of 64.7 ng g-1 dry weight and a detection rate of 93 %. Dimethoate was found
      to be the primary compound, followed by methyl parathion and parathion. The
      highest concentrations of OPPs were found in Jiangsu province due to the
      intensive agricultural activities. The pollution of OPPs is also highly
      associated with the land use types. The lower concentrations of OPPs found in
      vegetable fields could be attributed to their easy photodegradation and
      hydrolysis in aerobic soils. There was no significant difference in microbial
      communities among the sample sites, indicating that OPPs in agricultural soils of
      the YRD region cause negligible effects on microbiota. The risks of OPPs in the
      soils to human health were further evaluated. The hazard indexes in all the soil
      samples were below 1, suggesting absence of non-cancer risks. This study provides
      valuable information for a better understanding of the pollution status of OPPs
      in agricultural soils and a scientific basis for soil quality assessments.

PMID- 27687761
TI  - Development of a fuzzy-stochastic programming with Green Z-score criterion method
      for planning water resources systems with a trading mechanism.
AB  - This study developed a fuzzy-stochastic programming with Green Z-score criterion
      (FSGZ) method for water resources allocation and water quality management with a
      trading-mechanism (WAQT) under uncertainties. FSGZ can handle uncertainties
      expressed as probability distributions, and it can also quantify
      objective/subjective fuzziness in the decision-making process. Risk-averse
      attitudes and robustness coefficient are joined to express the relationship
      between the expected target and outcome under various risk preferences of
      decision makers and systemic robustness. The developed method is applied to a
      real-world case of WAQT in the Kaidu-Kongque River Basin in northwest China,
      where an effective mechanism (e.g., market trading) to simultaneously confront
      severely diminished water availability and degraded water quality is required.
      Results of water transaction amounts, water allocation patterns, pollution
      mitigation schemes, and system benefits under various scenarios are analyzed,
      which indicate that a trading-mechanism is a more sustainable method to manage
      water-environment crisis in the study region. Additionally, consideration of
      anthropogenic (e.g., a risk-averse attitude) and systemic factors (e.g., the
      robustness coefficient) can support the generation of a robust plan associated
      with risk control for WAQT when uncertainty is present. These findings assist
      local policy and decision makers to gain insights into water-environment capacity
      planning to balance the basin's social and economic growth with protecting the
      region's ecosystems.

PMID- 27687762
TI  - Temporal stability analysis of surface soil water content on two karst hillslopes
      in southwest China.
AB  - Knowledge of the temporal variability of soil water content (SWC) at the
      hillslope scale is essential for guiding rehabilitation strategies and for
      optimizing water resource management in the karst region of southwest China. This
      study aimed to use temporal stability analysis to upscale point-scale
      measurements to represent mean areal SWC on two typical karst hillslopes. Based
      on a grid sampling scheme (10 m * 10 m) applied to two 90 m * 120 m plots located
      on two hillslops, the SWC at a depth of 0-16 cm was measured 11-12 times across
      259 sampling points, using time domain reflectometry (TDR) from April 2011 to
      October 2012. Soil texture, bulk density (BD), saturated hydraulic conductivity
      (K s ), organic carbon (SOC), rock fragment content (RFC), and site elevation
      (SE) were also measured at these locations. Results showed the hillslope with
      more shrub cover was wetter than the hillslope with mixed grass-shrub cover. This
      difference was related to the differences in soil texture, soil hydraulic
      permeability, and topography. Through a comparison of values obtained with the
      Spearman correlation coefficient (r s ), standard deviation of mean relative
      difference (SDRD), and mean absolute bias error (MABE), we inferred that there is
      a higher degree of temporal stability for SWC in wet conditions than in drier
      conditions on the two hillslopes. Based on the values of the index of temporal
      stability (ITS), which combine the mean relative difference (MRD) and SDRD, the
      two locations were determined to be representative of mean SWC on both
      hillslopes. Moreover, these locations captured changes in mean SWC (NSCE = 0.69,
      and 0.65, and RMSE = 1.96, and 1.96 %, respectively). This demonstrates the
      feasibility of using the temporal stability of SWC to acquire mean SWC on karst
      hillslopes of southwestern China. The indirect method, which estimates mean SWC
      by considering the offset between the mean and the measurement value at a time
      stable location, predicted mean SWC (NSCE = 0.86, and 0.76, and RMSE = 1.29, and
      1.63 %, respectively) more precisely than the direct method (mean SWC directly
      measured at a time-stable location), because it eliminates deviation by
      introducing a constant offset (MRD). We recommended the use of the indirect
      method to acquire mean SWC values, when an allowable bias of 5 % for both MRD and
      SDRD can not be achieved. In addition, we found that soil texture, RFC, and
      elevation affect the pattern of SWC on the shrub hillslope. These results are
      expected to be useful for monitoring soil water dynamics on karst hillslopes,
      especially for restoration purposes.

PMID- 27687763
TI  - Erratum to: Biochemical biomarker responses to pollution in selected sentinel
      organisms across the Eastern Mediterranean and the Black Sea.

PMID- 27687764
TI  - Role of Spirulina in mitigating hemato-toxicity in Swiss albino mice exposed to
      aluminum and aluminum fluoride.
AB  - Aluminum is ingested through foods, water, air, and even drugs. Its intake is
      potentiated further through foods and tea prepared in aluminum utensils and Al
      salt added in the drinking water for removal of suspended impurities and also
      fluoride in the affected areas. The ameliorating role of a blue green alga
      Spirulina is well documented to various pollutants in the animal models. We,
      therefore, examined its protective role (230 mg/kg body weight) on the hematology
      of male Swiss albino mice treated with aluminum (sub-acute = 78.4 mg/kg body
      weight for 7 days, sub-chronic = 7.8 mg/kg body weight for 90 days) and aluminum
      fluoride (sub-acute = 103 mg/kg body weight, sub-chronic = 21 mg/kg body weight),
      along with their recovery after 90 days of sub-chronic exposure. This study
      revealed significant reduction in the values of RBC (5-18 %), Hb (15-17 %), PCV
      (8-14 %), and platelets (26-36 %), and increase in WBC (54-124 %) in the treated
      mice, particularly after sub-acute exposure. Aluminum fluoride was comparatively
      more toxic than aluminum. Further, Spirulina supplement not only alleviated
      toxicity of test chemicals in Swiss albino mice but also led to their better
      recovery after withdrawal.

PMID- 27687765
TI  - Unleashing the potential of ligninolytic bacterial contributions towards pulp and
      paper industry: key challenges and new insights.
AB  - Lignocellulose biomass predominantly constitutes the main feedstock for pulp and
      paper industry. Though some products of pulp and paper industry require the
      presence of lignin content, for most of the useful products formation lies in the
      efficient and selective removal of lignin component to make use of the intact
      cellulose fraction during the pretreatment of pulp. Lignin is a recalcitrant
      heteropolymer comprised of several complex stable bonds and linkages. The
      chemicals or intense energy processes used for delignification process release
      the hazardous chemicals compounds in the wastewater which cause toxicity and
      environmental pollution. The implementation of bacterial species has elucidated
      an effective approach in the generation of value-added products while degrading
      lignin from pulp biomass as well as detoxification of effluent. The direct use of
      bacterial cells in lignocellulose biomass and wastewater streams is promising as
      it outperforms the practical and technical constraints largely confronted by
      fungal and enzymatic means. The present review paper thus unleashed the potential
      of ligninolytic bacteria towards delignification of pulp biomass and treatment of
      effluent together with bioconversion of biomass and lignin into value-added
      products. Graphical abstract Schematic illustration of potential possible
      contribution of ligninolytic bacteria towards pulp and paper industry.

PMID- 27687766
TI  - Auditory cortical field coding long-lasting tonal offsets in mice.
AB  - Although temporal information processing is important in auditory perception, the
      mechanisms for coding tonal offsets are unknown. We investigated cortical
      responses elicited at the offset of tonal stimuli using flavoprotein fluorescence
      imaging in mice. Off-responses were clearly observed at the offset of tonal
      stimuli lasting for 7 s, but not after stimuli lasting for 1 s. Off-responses to
      the short stimuli appeared in a similar cortical region, when conditioning tonal
      stimuli lasting for 5-20 s preceded the stimuli. MK-801, an inhibitor of NMDA
      receptors, suppressed the two types of off-responses, suggesting that
      disinhibition produced by NMDA receptor-dependent synaptic depression might be
      involved in the off-responses. The peak off-responses were localized in a small
      region adjacent to the primary auditory cortex, and no frequency-dependent shift
      of the response peaks was found. Frequency matching of preceding tonal stimuli
      with short test stimuli was not required for inducing off-responses to short
      stimuli. Two-photon calcium imaging demonstrated significantly larger neuronal
      off-responses to stimuli lasting for 7 s in this field, compared with off
      responses to stimuli lasting for 1 s. The present results indicate the presence
      of an auditory cortical field responding to long-lasting tonal offsets, possibly
      for temporal information processing.

PMID- 27687767
TI  - Perspectives in neonatal and childhood arterial ischemic stroke.
AB  - INTRODUCTION: Over the last decade considerable advances have been made in the
      identification, understanding and management of pediatric arterial ischemic
      stroke. Such increasing knowledge has also brought new perspectives and
      interrogations in the current acute and rehabilitative care of these patients.
      Areas covered: In developed countries, focal cerebral arteriopathy is one of the
      most common causes of arterial ischemic stroke in childhood and imaging features
      are well characterized. However, there are ongoing debates regarding its
      underlying mechanisms, natural evolution and proper management. The
      implementation of thrombolytic therapy in acute pediatric stroke has been shown
      to be efficient in anecdotal cases but is still limited by a number of caveats,
      even in large tertiary centers. Finally, neonatal stroke represents a unique
      circumstance of possible early intervention before the onset of any neurological
      disability but this appears meaningful only in a selective group of neonates.
      Expert commentary: While perinatal stroke, a leading cause of cerebral palsy,
      appears to be multifactorial, a large number of childhood ischemic stroke are
      probably essentially triggered by infectious factors leading to vessel wall
      damage. Current research is aiming at better identifying risk factors in both
      conditions, and to define optimal acute and preventive therapeutic strategies in
      order to reduce significant long-term morbidity.

PMID- 27687768
TI  - Angiotensin-(1-7) abrogates angiotensin II-induced proliferation, migration and
      inflammation in VSMCs through inactivation of ROS-mediated PI3K/Akt and MAPK/ERK
      signaling pathways.
AB  - The proliferation, migration and inflammation of vascular smooth muscle cells
      (VSMCs) contribute to the pathogenesis and progression of several cardiovascular
      diseases such as atherosclerosis and hypertension. Angiotensin (Ang)-(1-7) and
      Ang II are identified to be involved in regulating cardiovascular activity. The
      present study is designed to determine the interaction between Ang-(1-7) and Ang
      II on VSMCs proliferation, migration and inflammation as well as their underlying
      mechanisms. We found that Ang-(1-7) significantly suppressed the positive effects
      of Ang II on VSMCs proliferation, migration and inflammation, as well as on
      induction of the phosphorylation of Akt and ERK1/2 and increase of superoxide
      anion level and NAD(P)H oxidase activity in VSMCs, whereas Ang-(1-7) alone had no
      significant effects. This inhibitory effects of Ang-(1-7) were abolished by Mas
      receptor antagonist A-779. In addition, Ang II type 1 (AT1) receptor antagonist
      losartan, but not A-779, abolished Ang II induced VSMCs proliferation, migration
      and inflammation responses. Furthermore, superoxide anion scavenger N-acetyl-L
      cysteine (NAC) or NAD(P)H oxidase inhibitor apocynin inhibited Ang II-induced
      activation of Akt and ERK1/2 signaling. These results indicate that Ang-(1-7)
      antagonizes the Ang II-induced VSMC proliferation, migration and inflammation
      through activation of Mas receptor and then suppression of ROS-dependent PI3K/Akt
      and MAPK/ERK signaling pathways.

PMID- 27687770
TI  - Collective modes in multi-Weyl semimetals.
AB  - We investigate collective modes in three dimensional (3D) gapless multi-Weyl
      semimetals with anisotropic energy band dispersions (i.e., with a positive
      integer J). For comparison, we also consider the gapless semimetals with the
      isotropic band dispersions (i.e. E ~ kJ). We calculate analytically long
      wavelength plasma frequencies incorporating interband transitions and chiral
      properties of carriers. For both the isotropic and anisotropic cases, we find
      that interband transitions and chirality lead to the depolarization shift of
      plasma frequencies. For the isotropic parabolic band dispersion the long
      wavelength plasmons do not decay via Landau damping, while for the higher-order
      band dispersions the long-wavelength plasmons experience damping below a critical
      density. For systems with the anisotropic dispersion the density dependence of
      the long-wavelength plasma frequency along the direction of non-linear dispersion
      behaves like that of the isotropic linear band model, while along the direction
      of linear dispersion it behaves like that of the isotropic non-linear model.
      Plasmons along both directions remain undamped over a broad range of densities
      due to the chirality induced depolarization shift. Our results provide a
      comprehensive picture of how band dispersion and chirality affect plasmon
      behaviors in 3D gapless chiral systems with the arbitrary band dispersion.

PMID- 27687769
TI  - Ultrasound and MRI predictors of surgical bowel resection in pediatric Crohn
      disease.
AB  - BACKGROUND: Imaging predictors for surgery in children with Crohn disease are
      lacking. OBJECTIVE: To identify imaging features of the terminal ileum on short
      interval bowel ultrasound (US) and MR enterography (MRE) in children with Crohn
      disease requiring surgical bowel resection and those managed by medical therapy
      alone. MATERIALS AND METHODS: This retrospective study evaluated patients 18
      years and younger with Crohn disease undergoing short-interval bowel US and MRE
      (within 2 months of one another), as well as subsequent ileocecectomy or
      endoscopy within 3 months of imaging. Appearance of the terminal ileum on both
      modalities was compared between surgical patients and those managed with medical
      therapy, with the following parameters assessed: bowel wall thickness, mural
      stratification, vascularity, fibrofatty proliferation, abscess, fistula and
      stricture on bowel US; bowel wall thickness, T2 ratio, enhancement pattern,
      mesenteric edema, fibrofatty proliferation, abscess, fistula and stricture on
      MRE. A two-sided t-test was used to compare means, a Mann-Whitney U analysis was
      used for non-parametric parameter scores, and a chi-square or two-sided Fisher
      exact test compared categorical variables. Imaging findings in surgical patients
      were correlated with location-matched histopathological scores of inflammation
      and fibrosis using a scoring system adapted from the Simple Endoscopic Score for
      Crohn Disease, and a Spearman rank correlation coefficient was used to compare
      inflammation and fibrosis on histopathology. RESULTS: Twenty-two surgical
      patients (mean age: 16.5 years; male/female: 13/9) and 20 nonsurgical patients
      (mean age: 14.8; M/F: 8/12) were included in the final analysis. On US, the
      surgical group demonstrated significantly increased mean bowel wall thickness
      (6.1 mm vs. 4.7 mm for the nonsurgical group; P = 0.01), loss of mural
      stratification (odds ratio [OR] = 6.3; 95% confidence interval [CI]: 1.4-28.4; P
      = 0.02) and increased fibrofatty proliferation (P = 0.04). On MRE, the surgical
      group showed increased mean bowel wall thickness (9.1 mm vs. 7.2 mm for the
      nonsurgical group; P = 0.02), increased mean T2 ratio (4.6 vs. 3.6 for the
      nonsurgical group; P = 0.03), different enhancement patterns (P = 0.03),
      increased mesenteric edema (P = 0.001) and increased stricture formation (OR =
      8.2; 95% CI: 1.8-36.4; P = 0.005). Nineteen of 22 ileocecectomy specimens showed
      severe inflammation and 21/22 showed severe fibrosis, with significant
      correlation between inflammation and fibrosis scores (rho = 0.55; P = 0.008);
      however, correlation with imaging findings was limited by the uniformity of
      findings on histopathology. CONCLUSION: Children with terminal ileal Crohn
      disease requiring surgical bowel resection demonstrate more severe manifestations
      of imaging features traditionally associated with both active inflammation and
      chronic fibrosis than those managed medically on US and MRE, findings that are
      corroborated by histopathology. These features may potentially serve as imaging
      biomarkers indicating the necessity for surgical intervention.

PMID- 27687772
TI  - A ketone/alcohol polymer for cycle of electrolytic hydrogen-fixing with water and
      releasing under mild conditions.
AB  - Finding a safe and efficient carrier of hydrogen is a major challenge. Recently,
      hydrogenated organic compounds have been studied as hydrogen storage materials
      because of their ability to stably and reversibly store hydrogen by forming
      chemical bonds; however, these compounds often suffer from safety issues and are
      usually hydrogenated with hydrogen at high pressure and/or temperature. Here we
      present a ketone (fluorenone) polymer that can be moulded as a plastic sheet and
      fixes hydrogen via a simple electrolytic hydrogenation at -1.5 V (versus Ag/AgCl)
      in water at room temperature. The hydrogenated alcohol derivative (the fluorenol
      polymer) reversibly releases hydrogen by heating (80  degrees C) in the presence
      of an aqueous iridium catalyst. Both the use of a ketone polymer and the
      efficient hydrogen fixing with water as a proton source are completely different
      from other (de)hydrogenated compounds and hydrogenation processes. The easy
      handling and mouldable polymers could suggest a pocketable hydrogen carrier.

PMID- 27687771
TI  - CSL protein regulates transcription of genes required to prevent catastrophic
      mitosis in fission yeast.
AB  - For every eukaryotic cell to grow and divide, intricately coordinated action of
      numerous proteins is required to ensure proper cell-cycle progression. The
      fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the
      fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell
      untimely torn) genes cause failed coordination between cell and nuclear division,
      resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL
      transcription factor gene, triggers a 'cut' phenotype, but the precise role of
      Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly
      activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and
      the biotin uptake/biosynthesis genes vht1 and bio2, with the former 2 implicated
      in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response
      element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows
      apparent oscillations during the cell cycle using temperature-sensitive cdc25-22
      and cdc10-M17 block-release experiments, but not with other synchronization
      methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is
      nutrient-dependent. We also show that drastic decrease in biotin availability
      arrests cell proliferation but does not cause mitotic defects. Taken together,
      our results raise the possibility that CSL proteins play conserved roles in
      regulating cell-cycle progression, and they could guide experiments into mitotic
      CSL functions in mammals.

PMID- 27687773
TI  - Plant virus infections control stomatal development.
AB  - Stomata are important regulators of carbon dioxide uptake and transpirational
      water loss. They also represent points of vulnerability as bacterial and fungal
      pathogens utilise this natural opening as an entry portal, and thus have an
      increasingly complex relationship. Unlike the situation with bacterial and fungal
      pathogens, we know very little about the role of stomata in viral infection. Here
      we report findings showing that viral infection influences stomatal development
      in two susceptible host systems (Nicotiana tabacum with TMV (Tobacco mosaic
      virus), and Arabidopsis thaliana with TVCV (Turnip vein-clearing virus)), but not
      in resistant host systems (Nicotiana glutinosa and Chenopodium quinoa with TMV).
      Virus infected plants had significantly lower stomatal indices in systemic leaves
      of susceptible systems; N. tabacum 9.8% reduction and A. thaliana 12.3%
      reduction, but not in the resistant hosts. Stomatal density in systemic leaves
      was also significantly reduced in virus infected A. thaliana by 19.6% but not in
      N. tabacum or the resistant systems. In addition, transpiration rate was
      significantly reduced in TMV infected N. tabacum.

PMID- 27687774
TI  - Clinical characteristics of women with reproductive cycle-associated bipolar
      disorder symptoms.
AB  - OBJECTIVE: Although there is clear evidence that reproductive cycle events are
      associated with mood episodes for women with bipolar disorder, few studies have
      examined for relationships between these and specific clinical characteristics of
      the disorder. This study aimed to explore the relationship between mood symptoms
      associated with reproductive cycle events and features of the disorder indicative
      of a more severe lifetime course. METHOD: Totally, 158 women of at least 18 years
      of age participated in the study. Subjects were recruited through a specialist
      clinic at the Black Dog Institute, Sydney, Australia. RESULTS: In total, 77% of
      women reported increases in mood symptoms during perimenstrual, postnatal or
      menopausal periods. These women had an earlier age of onset for depressive and
      hypo/manic episodes and a greater likelihood of comorbid anxiety disorders, rapid
      cycling and mixed mood compared to those who did not report such reproductive
      cycle-associated mood changes. Women who experienced postnatal episodes were also
      more likely to experience worse mood symptoms perimenstrually and menopausally.
      CONCLUSION: First, reproductive cycle event-related worsening of mood was
      associated with a more severe lifetime course of bipolar disorder, and, second,
      it appears that some women have a greater propensity to mood worsening at each of
      these reproductive cycle events. If replicated, these findings provide important
      information for clinicians treating women with reproductive cycle event mood
      changes and highlight the need for improved therapeutics for such presentations.

PMID- 27687775
TI  - Raloxifene for schizophrenia and symptoms of hyperprolactinaemia?

PMID- 27687776
TI  - Australia should be initiating a psychedelic research program: What are the
      barriers?

PMID- 27687777
TI  - Commentary on RANZCP clinical practice guidelines for the management of
      schizophrenia and related disorders - Section on pregnancy and schizophrenia.

PMID- 27687778
TI  - Mirtazapine-associated peripheral oedema.

PMID- 27687779
TI  - Antineuronal antibody screening in early onset-cognitive decline.

PMID- 27687781
TI  - Distribution and Adsorption of Ionic Species into a Liposome Membrane and Their
      Dependence upon the Species and Concentration of a Coexisting Counterion.
AB  - The distribution of ions into a bilayer lipid membrane (BLM) and their adsorption
      on the BLM are investigated by extracting a hydrophobic cation, rhodamine 6G
      (R6G+), into a liposome through the dialysis membrane method. R6G+ distribution
      mainly depends upon the concentration of the coexisting anion and its species (Cl
      , Br-, BF4-, ClO4-, and picrate). On the other hand, R6G+ adsorption on the BLM
      surface follows the Langmuir adsorption model and is independent of the
      coexisting anion in the aqueous phase. We propose an extraction model of ionic
      species into the BLM, to explain the dependence of extraction of ionic species
      upon the coexisting anion. In this model, an ion is distributed with a coexisting
      counterion into the BLM and then forms an ion pair in the BLM. Here, the ion
      adsorption equilibrium on the BLM surface is independent of the species and
      concentration of the coexisting counterion under the same ionic strength. On the
      basis of this model, we estimate the distribution constant of R6G+ and anion
      (KD), the ion-pair formation constant in the BLM (Kip), and the R6G+ adsorption
      constant on the BLM surface (Kad). Even for an ultrathin membrane system, such as
      a BLM, R6G+ is distributed with a coexisting counterion and the distribution
      equilibrium of the ionic species at the water-BLM interface is analyzable similar
      to that at the water-organic solvent interface.

PMID- 27687780
TI  - Single-cell RNA sequencing reveals dynamic changes in A-to-I RNA editome during
      early human embryogenesis.
AB  - BACKGROUND: A-to-I RNA-editing mediated by ADAR (adenosine deaminase acting on
      RNA) enzymes that converts adenosine to inosine in RNA sequence can generate
      mutations and alter gene regulation in metazoans. Previous studies have shown
      that A-to-I RNA-editing plays vital roles in mouse embryogenesis. However, the
      RNA-editing activities in early human embryonic development have not been
      investigated. RESULTS: Here, we characterized genome-wide A-to-I RNA-editing
      activities during human early embryogenesis by profiling 68 single cells from 29
      human embryos spanning from oocyte to morula stages. We demonstrate dynamic
      changes in genome-wide RNA-editing during early human embryogenesis in a stage
      specific fashion. In parallel with ADAR expression level changes, the genome-wide
      A-to-I RNA-editing levels in cells remained relatively stable until 4-cell stage,
      but dramatically decreased at 8-cell stage, continually decreased at morula
      stage. We detected 37 non-synonymously RNA-edited genes, of which 5 were
      frequently found in cells of multiple embryonic stages. Moreover, we found that A
      to-I editings in miRNA-targeted regions of a substantial number of genes
      preferably occurred in one or two sequential stages. CONCLUSIONS: Our single-cell
      analysis reveals dynamic changes in genome-wide RNA-editing during early human
      embryogenesis in a stage-specific fashion, and provides important insights into
      early human embryogenesis.

PMID- 27687782
TI  - Giant superconducting fluctuations in the compensated semimetal FeSe at the BCS
      BEC crossover.
AB  - The physics of the crossover between weak-coupling Bardeen-Cooper-Schrieffer
      (BCS) and strong-coupling Bose-Einstein condensate (BEC) limits gives a unified
      framework of quantum-bound (superfluid) states of interacting fermions. This
      crossover has been studied in the ultracold atomic systems, but is extremely
      difficult to be realized for electrons in solids. Recently, the superconducting
      semimetal FeSe with a transition temperature Tc=8.5 K has been found to be deep
      inside the BCS-BEC crossover regime. Here we report experimental signatures of
      preformed Cooper pairing in FeSe, whose energy scale is comparable to the Fermi
      energies. In stark contrast to usual superconductors, large non-linear
      diamagnetism by far exceeding the standard Gaussian superconducting fluctuations
      is observed below T*~20 K, providing thermodynamic evidence for prevailing phase
      fluctuations of superconductivity. Nuclear magnetic resonance and transport data
      give evidence of pseudogap formation at ~T*. The multiband superconductivity
      along with electron-hole compensation in FeSe may highlight a novel aspect of the
      BCS-BEC crossover physics.

PMID- 27687783
TI  - Increased GABAB receptor signaling in a rat model for schizophrenia.
AB  - Schizophrenia is a complex disorder that affects cognitive function and has been
      linked, both in patients and animal models, to dysfunction of the GABAergic
      system. However, the pathophysiological consequences of this dysfunction are not
      well understood. Here, we examined the GABAergic system in an animal model
      displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS)
      rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat
      at postnatal day 20-22. We found changes in the expression of the GABA
      synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic
      region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory
      function in this region in APO-SUS rats. While we did not observe changes in
      basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS
      compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter
      stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this
      reduction, indicating that the decreased paired-pulse ratio was caused by
      increased GABAB signaling. Consistently, we find an increased expression of the
      GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence
      for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further
      supporting an important role for the GABAergic system in the pathophysiology of
      schizophrenia.

PMID- 27687786
TI  - Assessment of average of normals (AON) procedure for outlier-free datasets
      including qualitative values below limit of detection (LoD): an application
      within tumor markers such as CA 15-3, CA 125, and CA 19-9.
AB  - Average of normals (AON) is a quality control procedure that is sensitive only to
      systematic errors that can occur in an analytical process in which patient test
      results are used. The aim of this study was to develop an alternative model in
      order to apply the AON quality control procedure to datasets that include
      qualitative values below limit of detection (LoD). The reported patient test
      results for tumor markers, such as CA 15-3, CA 125, and CA 19-9, analyzed by two
      instruments, were retrieved from the information system over a period of 5
      months, using the calibrator and control materials with the same lot numbers. The
      median as a measure of central tendency and the median absolute deviation (MAD)
      as a measure of dispersion were used for the complementary model of AON quality
      control procedure. The ubias values, which were determined for the bias component
      of the measurement uncertainty, were partially linked to the percentages of the
      daily median values of the test results that fall within the control limits. The
      results for these tumor markers, in which lower limits of reference intervals are
      not medically important for clinical diagnosis and management, showed that the
      AON quality control procedure, using the MAD around the median, can be applied
      for datasets including qualitative values below LoD.

PMID- 27687785
TI  - An original pharmacoepidemiological-pharmacodynamic method: application to
      antipsychotic-induced movement disorders.
AB  - AIMS: Pharmacovigilance databases are usually used to detect new potential
      signals that are relevant for drug safety. They are seldom used for explanatory
      purposes, e.g. to understand the mechanisms of adverse drug reactions (ADRs). The
      aim of the present study was to combine pharmacovigilance and pharmacodynamic
      data to investigate the association between dopamine D2, serotonin 5HT2A, and
      muscarinic M1 receptor occupancy and the risks of antipsychotic drug (AP)-induced
      movement disorders. METHODS: First, we performed a case-noncase analysis using
      spontaneous reports from the World Health Organization (WHO) Global Individual
      Case Safety Report (ICSR) database, VigiBase(r). We thus measured the risk of
      reporting movement disorders compared with all other ADRs [expressed as a
      reporting odds ratio (ROR)] for APs. Second, we performed a linear regression
      analysis to explore the association between the estimated risk of reporting for
      individual drugs and their receptor occupancy properties, for D2, 5HT2A and M1
      receptors. RESULTS: Compared with second-generation APs, first-generation APs
      were found to be significantly more associated with the reporting of movement
      disorders in general but also with dystonia, Parkinsonism, akathisia and tardive
      dyskinesia, irrespective of gender. A significant inverse correlation was found
      between the ROR for movement disorders and the receptor occupancy of 5HT2A [P <
      0.001; R2  = 0.51; slope = -0.014; 95% confidence interval (CI) (-0.029, 0.001)],
      M1 (P < 0.001; R2  = 0.56; slope = -0.014; 95% CI (-0.028, 0.001) but not D2
      dopamine (P = 0.54; R2  = 0.02; slope = -0.003; 95% CI (-0.007, 0.001) receptors.
      CONCLUSIONS: Using the example of AP-induced movement disorders, the present
      study underlines the value of the pharmacoepidemiological-pharmacodynamic method
      to explore ADR mechanisms in humans and real-life settings.

PMID- 27687787
TI  - Illness perception in patients with coronary artery disease: A systematic review.
AB  - The aim of this study was to conduct a systematic review that investigates the
      differences in illness perception with age and gender in patients diagnosed with
      coronary artery disease. Previous studies show some discrepancies regarding the
      influence of age and gender on the specific dimensions of coronary artery disease
      patients' illness perception. A systematic review using a narrative synthesis
      process included preliminary synthesis, exploration of relationships and
      assessment of the robustness of the synthesis and findings was conducted. Search
      terms were used to identify research studies published between 1996 and December
      2014 across four key databases: CINAHL, Medline, PsycINFO and Web of Science. A
      total of 14 studies met the inclusion criteria of the review. The review found
      that men had a stronger perception that their own behaviour had caused their
      illness than women. In addition, older patients had lower perceptions of the
      consequences and chronicity of their illness. This analysis concludes that some
      dimensions of illness perception vary according to age and gender of patients
      with coronary artery disease. These differences should be taken into
      consideration, particularly when providing health education and cardiac
      rehabilitation.

PMID- 27687784
TI  - Addressing the inter-individual variation in response to consumption of plant
      food bioactives: Towards a better understanding of their role in healthy aging
      and cardiometabolic risk reduction.
AB  - Bioactive compounds in plant-based foods have health properties that contribute
      to the prevention of age-related chronic diseases, particularly cardiometabolic
      disorders. Conclusive proof and understanding of these benefits in humans is
      essential in order to provide effective dietary recommendations but, so far, the
      evidence obtained from human intervention trials is limited and contradictory.
      This is partly due to differences between individuals in the absorption,
      distribution, metabolism and excretion of bioactive compounds, as well as to
      heterogeneity in their biological response regarding cardiometabolic health
      outcomes. Identifying the main factors underlying inter-individual differences,
      as well as developing new and innovative methodologies to account for such
      variability constitute an overarching goal to ultimately optimize the beneficial
      health effects of plant food bioactives for each and every one of us. In this
      respect, this position paper from the COST Action FA1403-POSITIVe examines the
      main factors likely to affect the individual responses to consumption of plant
      food bioactives and presents perspectives for assessment and consideration of
      inter-individual variability.

PMID- 27687788
TI  - Right ventricular myxoma originating from a papillary muscle: a case report.
AB  - Very few cases of ventricular myxoma originate from a papillary muscle. Patients
      with a cardiac myxoma and a history of colorectal carcinoma are also rare. Here,
      we present a case of an extremely large right ventricular myxoma that originated
      from the posteromedial papillary muscle in a patient with a history of colorectal
      carcinoma.

PMID- 27687790
TI  - 3D human tissue culture: modeling environmental effects on the stem cell
      epigenome.

PMID- 27687789
TI  - Bioaerosols in the Barcelona subway system.
AB  - Subway systems worldwide transport more than 100 million people daily; therefore,
      air quality on station platforms and inside trains is an important urban air
      pollution issue. We examined the microbiological composition and abundance in
      space and time of bioaerosols collected in the Barcelona subway system during a
      cold period. Quantitative PCR was used to quantify total bacteria, Aspergillus
      fumigatus, influenza A and B, and rhinoviruses. Multitag 454 pyrosequencing of
      the 16S rRNA gene was used to assess bacterial community composition and
      biodiversity. The results showed low bioaerosol concentrations regarding the
      targeted microorganisms, although the bacterial bioburden was rather high (104
      bacteria/m3 ). Airborne bacterial communities presented a high degree of overlap
      among the different subway environments sampled (inside trains, platforms, and
      lobbies) and were dominated by a few widespread taxa, with Methylobacterium being
      the most abundant genus. Human-related microbiota in sequence dataset and
      ascribed to potentially pathogenic bacteria were found in low proportion (maximum
      values below 2% of sequence readings) and evenly detected. Hence, no important
      biological exposure marker was detected in any of the sampled environments.
      Overall, we found that commuters are not the main source of bioaerosols in the
      Barcelona subway system.

PMID- 27687791
TI  - Needle Trap Device as a New Sampling and Preconcentration Approach for Volatile
      Organic Compounds of Herbal Medicines and its Application to the Analysis of
      Volatile Components in Viola tianschanica.
AB  - INTRODUCTION: The needle trap device (NTD) technique is a new microextraction
      method for sampling and preconcentration of volatile organic compounds (VOCs).
      Previous NTD studies predominantly focused on analysis of environmental volatile
      compounds in the gaseous and liquid phases. Little work has been done on its
      potential application in biological samples and no work has been reported on
      analysis of bioactive compounds in essential oils from herbal medicines.
      OBJECTIVE: The main purpose of the present study is to develop a NTD sampling
      method for profiling VOCs in biological samples using herbal medicines as a case
      study. METHODOLOGY: A combined method of NTD sample preparation and gas
      chromatography-mass spectrometry was developed for qualitative analysis of VOCs
      in Viola tianschanica. A 22-gauge stainless steel, triple-bed needle packed with
      Tenax, Carbopack X and Carboxen 1000 sorbents was used for analysis of VOCs in
      the herb. Furthermore, different parameters affecting the extraction efficiency
      and capacity were studied. RESULTS: The peak capacity obtained by NTDs was 104,
      more efficient than those of the static headspace (46) and hydrodistillation
      (93). This NTD method shows potential to trap a wide range of VOCs including the
      lower and higher volatile components, while the static headspace and
      hydrodistillation only detects lower volatile components, and semi-volatile and
      higher volatile components, respectively. CONCLUSION: The developed NTD sample
      preparation method is a more rapid, simpler, convenient, and sensitive
      extraction/desorption technique for analysis of VOCs in herbal medicines than the
      conventional methods such as static headspace and hydrodistillation. Copyright
      (c) 2016 John Wiley & Sons, Ltd.

PMID- 27687792
TI  - Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus
      Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and
      Entecavir: a 24-Month Prospective Study.
AB  - BACKGROUND & AIM: Search for an effective therapy for patients with hepatitis B
      virus related acute-on-chronic liver failure (HBV-ACLF) remains an important
      issue. This study investigated the efficacy of umbilical cord-derived mesenchymal
      stem cell (UC-MSC) transplantation in patients with HBV-ACLF. METHODS: 45
      consecutive entecavir-treated HBV-ACLF patients were prospectively studied. Among
      these patients, 11 received both plasma exchange (PE) and a single
      transplantation of UC-MSCs (group A), while 34 received only PE (group B). The
      primary endpoint was survival at 24 months. RESULTS: Compared with group B,
      levels of albumin, alanine aminotransferase, aspartate aminotransferase, total
      bilirubin, direct bilirubin, prothrombin time (PT), international normalized
      ratio (INR) and model for end-stage liver disease score in group A improved
      significantly at 4 weeks after transplantation (p < 0.05). Levels of albumin, PT
      and INR in group A were also markedly improved at 24 months (p < 0.05). Group A
      had significantly higher cumulative survival rate at 24 months (54.5 % v.s. 26.5
      %, p = 0.015 by log rank test). Between the two groups, levels of creatinine,
      White blood cell, hemoglobin and platelet were similar. HBeAg loss and
      hepatocellular carcinoma incidence were similar at 24 months. Group assignment
      (relative risk: 2.926, 95%confidence interval: 1.043-8.203, p = 0.041) was an
      independent predictor for survival at 24 months. Success rate of UC-MSC
      transplantation was 100 % in group A. No severe adverse event was observed in any
      patient. CONCLUSION: UC-MSC transplantation is safe and effective for HBV-ACLF
      patients treated with PE and entecavir. It further improves the hepatic function
      and survival.

PMID- 27687793
TI  - Bcl-xL inhibition - a novel strategy for glioma therapy.

PMID- 27687794
TI  - Unique growth paths of heterospecific pollen tubes result in late entry into
      ovules in the gynoecium of Sagittaria (Alismataceae).
AB  - Pollen-pistil interactions are a fundamental process in the reproductive biology
      of angiosperms and play a particularly important role in maintaining incipient
      species that exist in sympatry. However, the majority of previous studies have
      focused on species with syncarpous gynoecia (fused carpels) and not those with
      apocarpous gynoecia (unfused carpels). In the present study, we investigated the
      growth of conspecific pollen tubes compared to heterospecific pollen tubes in
      Sagittaria species, which have apocarpous gynoecia. We conducted controlled
      pollinations between S. pygmaea and S. trifolia and observed the growth of
      conspecific and heterospecific pollen tubes under a fluorescence microscope.
      Heterospecific and conspecific pollen tubes arrived at locules within the ovaries
      near simultaneously. However, conspecific pollen tubes entered into the ovules
      directly, whereas heterospecific tubes passed through the carpel base and
      adjacent receptacle tissue, to ultimately fertilize other unfertilized ovules.
      This longer route taken by heterospecific pollen tubes therefore caused a delay
      in the time required to enter into the ovules. Furthermore, heterospecific pollen
      tubes displayed similar growth patterns at early and peak pollination. The growth
      pattern of heterospecific pollen tubes at late pollination was similar to that of
      conspecific pollen tubes at peak pollination. Heterospecific and conspecific
      pollen tubes took different routes to fertilize ovules. A delayed entry of
      heterospecific pollen into ovules may be a novel mechanism of conspecific pollen
      advantage (CPA) for apocarpous species.

PMID- 27687795
TI  - Improved calvarial bone repair by hASCs engineered with Cre/loxP-based
      baculovirus conferring prolonged BMP-2 and MiR-148b co-expression.
AB  - Repairing large calvarial bone defects remains a challenging task. Previously, it
      was discovered that that miR-148b, when acting in concert with bone morphogenetic
      protein 2 (BMP-2), enhanced the osteogenesis of human adipose-derived stem cells
      (hASCs) and improved calvarial bone healing in nude mice. However, the molecular
      target of miR-148b remained elusive. Here it is revealed that miR-148b directly
      targets NOG, whose gene product (noggin) is an antagonist to BMPs and negatively
      regulates BMP-induced osteogenic differentiation and bone formation. A new
      Cre/loxP-based baculovirus system was employed to drive prolonged BMP-2 and miR
      148b overexpression in hASCs, wherein the BMP-2 overexpression induced noggin
      expression but the concurrent miR-148b expression downregulated noggin, thus
      relieving the negative regulatory loop and ameliorating hASC osteogenesis without
      hindering hASC proliferation or triggering appreciable cytotoxicity. Implantation
      of the engineered hASCs coexpressing BMP-2 and miR-148b into nude mice enabled
      substantial repair of critical-size calvarial bone defects (4 mm diameter) at 12
      weeks post-transplantation, filling 83% of the defect area, 75% of bone volume
      and restoring the bone density to 89% of the original bone density. Such superior
      healing effects indicate the potential of the Cre/loxP-based baculovirus-mediated
      BMP-2/miR-148b expression for calvarial bone repair. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27687796
TI  - Practice, training, and research in neuropsychology in mainland China: challenges
      and opportunities.
AB  - OBJECTIVE: This is an invited paper for a special issue. The objective was to
      review history, educational and training pathways, licensure and board
      certification, practice and compensation, and unique aspects of, or challenges
      faced by, neuropsychology in mainland China. METHOD: Historical, scientific, and
      clinical literatures were reviewed and integrated. RESULTS: The history of
      neuropsychology in mainland China is traced back to the late 1930s. Educational
      pathways have not yet been fully formalized. Clinical practice generally occurs
      within rehabilitation settings, and medical license is required. The main
      challenge lies in the establishment of training guidelines and the expansion of
      neuropsychology to meet the tremendous needs of a large nation. CONCLUSIONS:
      Although the development and status of psychology has gradually gained momentum
      in mainland China, the development of neuropsychology has not shown significant
      advancement since the late 1930s.

PMID- 27687797
TI  - Histological investigation of common insensate flaps obtained from the hand and
      forearm regions for use in fingertip reconstruction.
AB  - OBJECTIVE: Many skin flaps have been described for fingertip reconstruction;
      however, they have not been compared histologically. The aim of this study is to
      compare the histological features of common insensate flaps that are used for
      fingertip reconstruction. METHOD: Skin from fingertips and common flap donor
      sites on the hand and forearm of cadavers were harvested. This study investigated
      four histological characteristics, namely thickness of the epidermis and dermis;
      the ratio of collagen to elastic fibres (C/E ratio) in subdermal tissues, and
      distribution densities of Merkel cells and Meissner's corpuscles. It then
      compared the values obtained to determine which flap donor site best matched the
      fingertip. RESULTS: Epidermal thickness of the reverse digital artery island
      flap, thenar flap, and hypothenar flap was similar to that of fingertip tissue;
      dermal thickness of the hypothenar flap was similar to that of fingertip tissue.
      The C/E ratio of the reverse digital artery island flap was similar to that of
      fingertip tissue. Merkel cells were abundant in the reverse digital artery island
      flap, but Meissner's corpuscles were few in each of the flaps compared with
      fingertip tissue. CONCLUSION: The flap donor site with histological properties
      most similar to fingertip tissue was the palmar lateral aspect at the finger
      base, representative of the reverse digital artery island flap with respect to
      epidermal thickness, C/E ratio, and presence of Merkel cells. The thenar and
      hypothenar flaps also showed similar properties.

PMID- 27687798
TI  - Erratum to: A clinical guidance tool to improve the care of children hospitalized
      with severe pneumonia in Lusaka, Zambia.

PMID- 27687799
TI  - What is the probability of replicating a statistically significant association in
      genome-wide association studies?
AB  - The goal of genome-wide association studies (GWASs) is to discover genetic
      variants associated with diseases/traits. Replication is a common validation
      method in GWASs. We regard an association as true finding when it shows
      significance in both primary and replication studies. A question worth pondering
      is what is the probability of a primary association (i.e. a statistically
      significant association in the primary study) being validated in the replication
      study? This article systematically reviews the answers to this question from
      different points of view. As Bayesian methods can help us integrate out the
      uncertainty about the underlying effect of the primary association, we will
      mainly focus on the Bayesian view in this article. We refer the Bayesian
      replication probability as the replication rate (RR). We further describe an
      estimation method for RR, which makes use of the summary statistics from the
      primary study. We can use the estimated RR to determine the sample size of the
      replication study and to check the consistency between the results of the primary
      study and those of the replication study. We describe an R-package to estimate
      and apply RR in GWASs. Simulation and real data experiments show that the
      estimated RR has good prediction and calibration performance. We also use these
      data to demonstrate the usefulness of RR. The R-package is available at
      http://bioinformatics.ust.hk/RRate.html.

PMID- 27687800
TI  - Participation of peripheral TRPV1, TRPV4, TRPA1 and ASIC in a magnesium sulfate
      induced local pain model in rat.
AB  - We previously showed that magnesium sulfate (MS) has systemic antinociceptive and
      local peripheral pronociceptive effects. The role of transient receptor potential
      (TRP) channels and acid-sensing ion channels (ASICs) in the mechanism of action
      of MS has not been investigated in detail. The aim of this study was to explore
      the participation of TRP channels in the pronociceptive action of MS in rats
      after its intraplantar injection. The paw withdrawal threshold (PWT) to
      mechanical stimuli was measured by the electronic von Frey test. Drugs that were
      tested were either co-administered with an isotonic pH-unadjusted or pH-adjusted
      solution of MS intraplantarily, or to the contralateral paw to exclude systemic
      effects. We found that the subcutaneous administration of both pH-adjusted (7.4)
      and pH-unadjusted (about 6.0) isotonic (6.2% w/v in water) solutions of MS induce
      the pain at the injection site. The pH-unadjusted MS solution-induced mechanical
      hyperalgesia decreased in a dose-dependent manner as a consequence of co
      injection of capsazepine, a selective TRPV1 antagonist (20, 100 and 500pmol/paw),
      RN-1734, a selective TRPV4 antagonist (1.55, 3.1 and 6.2MUmol/paw), HC-030031, a
      selective TRPA1 antagonist (5.6, 28.1 and 140nmol/paw), and amiloride
      hydrochloride, a non-selective ASIC inhibitor (0.83, 2.5 and 7.55MUmol/paw). In
      pH-adjusted MS-induced hyperalgesia, the highest doses of TRPV1, TRPV4 and TRPA1
      antagonists displayed effects that were, respectively, either similar, less
      pronounced or delayed in comparison to the effect induced by administration of
      the pH-unadjusted MS solution; the ASIC antagonist did not have any effect. These
      results suggest that the MS-induced local peripheral mechanical hyperalgesia is
      mediated via modulation of the activity of peripheral TRPV1, TRPV4, TRPA1 and
      ASICs. Specific local inhibition of TRP channels represents a novel approach to
      treating local injection-related pain.

PMID- 27687801
TI  - Exposure to alcohol during adolescence exerts long-term effects on stress
      response and the adult brain stress circuits.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis undergoes critical developments
      during adolescence. Therefore, stressors experienced during this period
      potentially have long-term effects on adult HPA axis function. We hypothesized
      that adolescent intermittent ethanol (AIE) exposure would affect adult HPA axis
      function, resulting in altered responses to an alcohol challenge in young adults
      or adults. To test these hypotheses, male rats were exposed to alcohol vapor for
      6h per day from post-natal day (PND) 28-42, then acutely challenged with alcohol
      intragastrically (3.2-4.5g/kg) in young adults (PND 70) or adults (PND 90).
      Overall, we observed blunted HPA axis responses to an alcohol challenge due to
      AIE exposure. Specifically, AIE tended to inhibit the alcohol challenge-induced
      increase in plasma corticosterone (CORT) concentrations in young adult and adult
      rats. As well, AIE significantly blunted the alcohol challenge-induced arginine
      vasopressin (Avp) mRNA expression in the paraventricular nucleus (PVN) of the
      hypothalamus of adult rats. Results of the present study are similar to what we
      have previously shown, that these changes in PVN responsiveness may result from
      AIE-induced alterations in adrenergic neurons in brain stem regions C1-C3 known
      to project to the PVN. AIE elevated the number of colocalized c
      fos/phenylethanolamine N-methyltransferase (PNMT)-positive cell bodies in the C1
      region of adult rats. Together, these data suggest that AIE exposure produces
      alterations in male HPA axis responsiveness to administration of an acute alcohol
      challenge that may be long-lasting.

PMID- 27687802
TI  - State-dependent variability of dynamic functional connectivity between
      frontoparietal and default networks relates to cognitive flexibility.
AB  - The brain is a dynamic, flexible network that continuously reconfigures. However,
      the neural underpinnings of how state-dependent variability of dynamic functional
      connectivity (vdFC) relates to cognitive flexibility are unclear. We therefore
      investigated flexible functional connectivity during resting-state and task-state
      functional magnetic resonance imaging (rs-fMRI and t-fMRI, resp.) and performed
      separate, out-of-scanner neuropsychological testing. We hypothesize that state
      dependent vdFC between the frontoparietal network (FPN) and the default mode
      network (DMN) relates to cognitive flexibility. Seventeen healthy subjects
      performed the Stroop color word test and underwent t-fMRI (Stroop computerized
      version) and rs-fMRI. Time series were extracted from a cortical atlas, and a
      sliding window approach was used to obtain a number of correlation matrices per
      subject. vdFC was defined as the standard deviation of connectivity strengths
      over these windows. Higher task-state FPN-DMN vdFC was associated with greater
      out-of-scanner cognitive flexibility, while the opposite relationship was present
      for resting-state FPN-DMN vdFC. Moreover, greater contrast between task-state and
      resting-state vdFC related to better cognitive performance. In conclusion, our
      results suggest that not only the dynamics of connectivity between these networks
      is seminal for optimal functioning, but also that the contrast between dynamics
      across states reflects cognitive performance.

PMID- 27687804
TI  - Gemcitabine reduces MDSCs, tregs and TGFbeta-1 while restoring the teff/treg
      ratio in patients with pancreatic cancer.
AB  - BACKGROUND: Cancer immunotherapy can be potentiated by conditioning regimens such
      as cyclophosphamide, which reduces the level of regulatory T cells (tregs).
      However, myeloid suppressive cells are still remaining. Accordingly to previous
      reports, gemcitabine improves immune status of cancer patients. In this study,
      the role of gemcitabine was further explored to map its immunological target
      cells and molecules in patients with pancreatic cancer. METHODS: Patient blood
      was investigated by flow cytometry and cytokine arrays at different time points
      during gemcitabine treatment. RESULTS: The patients had elevated myeloid-derived
      suppressor cells (MDSCs), and Tregs at diagnosis. Myeloid cells were in general
      decreased by gemcitabine. The granulocytic MDSCs were significantly reduced while
      monocytic MDSCs were not affected. In vitro, monocytes responding to IL-6 by
      STAT3 phosphorylation were prevented to respond in gemcitabine medium. However,
      gemcitabine could not prevent STAT3 phosphorylation in IL-6-treated tumor cell
      lines. TGFbeta-1 was significantly reduced after only one treatment and continued
      to decrease. At the same time, the effector T cell:Treg ratio was increased and
      the effector T cells had full proliferative capacity during the gemcitabine
      cycle. However, after a resting period, the level of suppressor cells and TGFbeta
      1 had been restored showing the importance of continuous conditioning.
      CONCLUSIONS: Gemcitabine regulates the immune system in patients with pancreatic
      cancer including MDSCs, Tregs and molecules such as TGFbeta-1 but does not hamper
      the ability of effector lymphocytes to expand to stimuli. Hence, it may be of
      high interest to use gemcitabine as a conditioning strategy together with
      immunotherapy.

PMID- 27687805
TI  - A Prospective Randomized Clinical Trial in Total Hip Arthroplasty-Comparing Early
      Results Between the Direct Anterior Approach and the Posterior Approach.
AB  - BACKGROUND: We report a prospective randomized study comparing early clinical
      results between the direct anterior approach (DAA) and posterior approach (PA) in
      primary hip arthroplasty. METHODS: Surgeries were performed by 2 senior hip
      arthroplasty surgeons. Seventy-two patients with complete data were assessed
      preoperatively 2, 6, and 12 weeks postoperatively. The primary outcomes were the
      Western Ontario McMasters Arthritis Index and Oxford Hip Scores. Secondary
      outcome measures included the EuroQoL, 10-meter walk test, and clinical and
      radiographic parameters. RESULTS: Data analyses showed no difference between DAA
      (n = 35) and PA (n = 37) groups when comparing total scores for primary outcomes.
      No significant differences were observed for 10-meter walk test, EuroQoL, and
      radiographic analyses. Subgroup analysis for surgeon 1 identified that the DAA
      group had shorter acute hospital stay, less postoperative opiate requirements,
      and smaller wounds. However, this was offset by increased operative time, higher
      intraoperative blood loss, and weaker hip flexion at 2 and 6 weeks. Subgroup
      analysis of items on the Western Ontario McMasters Arthritis Index and Oxford Hip
      Score identified that hip flexion activity favored the DAA group up to 6 weeks
      postoperatively. There was an 83% incidence of lateral cutaneous nerve of thigh
      neuropraxia at the 12-week mark in the DAA group. No neuropraxias occurred in the
      PA group. One dislocation occurred in each group. A single patient from the DAA
      group required reoperation for leg-length discrepancy. CONCLUSION: DAA total hip
      arthroplasty (THA) has comparable results with PA THA. Choice of surgical
      approach for THA should be based on patient factors, surgeon preference, and
      experience.

PMID- 27687806
TI  - Do Conversion Total Hip Arthroplasty Yield Comparable Results to Primary Total
      Hip Arthroplasty?
AB  - BACKGROUND: The incidence of hip fractures is growing with the increasing elderly
      population. Typically, hip fractures are treated with open reduction internal
      fixation, hemiarthroplasty, or total hip arthroplasty (THA). Failed hip fracture
      fixation is often salvaged by conversion THA. The total number of conversion THA
      procedures is also supplemented by its use in treating different failed surgical
      hip treatments such as acetabular fracture fixation, Perthes disease, slipped
      capital femoral epiphysis, and developmental dysplasia of the hip. As the
      incidence of conversion THA rises, it is important to understand the
      perioperative characteristics of conversion THA. Some studies have demonstrated
      higher complication rates in conversion THAs than primary THAs, but research
      distinguishing the 2 groups is still limited. METHODS: Perioperative data for 119
      conversion THAs and 251 primary THAs were collected at 2 centers. Multivariable
      linear regression was performed for continuous variables, multivariable logistic
      regression for dichotomous variables, and chi-square test for categorical
      variables. RESULTS: Outcomes for conversion THAs were significantly different (P
      < .05) compared to primary THA and had longer hospital length of stay (average
      3.8 days for conversion THA, average 2.8 days for primary THA), longer operative
      time (168 minutes conversion THA, 129 minutes primary THA), greater likelihood of
      requiring metaphysis/diaphysis fixation, and greater likelihood of requiring
      revision type implant components. CONCLUSION: Our findings suggest that
      conversion THAs require more resources than primary THAs, as well as advanced
      revision type components. Based on these findings, conversion THAs should be
      reclassified to reflect the greater burden borne by treatment centers.

PMID- 27687807
TI  - Drivers of the Variation in Prosthetic Implant Purchase Prices for Total Knee and
      Total Hip Arthroplasties.
AB  - BACKGROUND: Previous studies have documented wide variation in health care
      spending and prices; however, the causes for the variation in supply purchase
      prices across providers are not well understood. The purpose of this study was to
      determine the drivers of variation in prosthetic implant purchase prices for
      primary total knee and hip arthroplasties (TKA and THA, respectively) across
      providers. METHODS: We obtained retrospective data from 27 hospitals on the
      average prosthetic implant purchase prices for primary TKAs and THAs over the 12
      months ending September 30, 2013, as well as data on a range of independent
      potential explanatory variables. Each hospital performed at least 200 primary
      total joint arthroplasties per year. The multivariate seemingly unrelated
      regression approach was used to evaluate the impact of the variables on purchase
      price for each type of implant. RESULTS: The average purchase price at the
      hospital at the 90th percentile was 2.1 times higher for TKAs and 1.7 times
      higher for THAs than that at the hospital at the 10th percentile. The use of a
      hospital-physician committee for implant vendor selection and negotiation was
      associated with 17% and 23% lower implant purchase prices (P < .05) for TKAs and
      THAs, respectively, relative to hospitals that did not have this collaborative
      approach. CONCLUSION: The use of a joint hospital-physician committee is a
      potential strategy for achieving lower average purchase prices for prosthetic
      implants. Policies to increase hospital-physician collaboration may lead to lower
      average purchase prices in this market.

PMID- 27687803
TI  - Insight from animal models of environmentally driven epigenetic changes in the
      developing and adult brain.
AB  - The efforts of many neuroscientists are directed toward understanding the
      appreciable plasticity of the brain and behavior. In recent years, epigenetics
      has become a core of this focus as a prime mechanistic candidate for behavioral
      modifications. Animal models have been instrumental in advancing our
      understanding of environmentally driven changes to the epigenome in the
      developing and adult brain. This review focuses mainly on such discoveries driven
      by adverse environments along with their associated behavioral outcomes. While
      much of the evidence discussed focuses on epigenetics within the central nervous
      system, several peripheral studies in humans who have experienced significant
      adversity are also highlighted. As we continue to unravel the link between
      epigenetics and phenotype, discerning the complexity and specificity of
      epigenetic changes induced by environments is an important step toward
      understanding optimal development and how to prevent or ameliorate behavioral
      deficits bred by disruptive environments.

PMID- 27687808
TI  - The Influence of Cement Morphology Parameters on the Strength of the Cement-Bone
      Interface in Tibial Tray Fixation.
AB  - BACKGROUND: The strength of the cement-bone interface in tibial component
      fixation depends on the morphology of the cement mantle. The purpose of this
      study was to identify thresholds of cement morphology parameters to maximize
      fixation strength using a minimum amount of cement. METHODS: Twenty-three
      cadaveric tibiae were analyzed that had been implanted with tibial trays in
      previous studies and for which the pull-out strength of the tray had been
      measured. Specimens were separated into a group failing at the cement-bone
      interface (INTERFACE) and one failing in the bulk bone (BULK). Maximum pull-out
      strength corresponds to the ultimate strength of the bulk bone if the cement-bone
      interface is sufficiently strong. 3D models of the cement mantle in situ were
      reconstructed from computed tomography scans. The influences of bone mineral
      density and 6 cement morphology parameters (reflecting cement penetration, bone
      cement interface, cement volume) on pull-out strength of the BULK group were
      determined using multiple regression analysis. The threshold of each parameter
      for classification of the specimens into either group was determined using
      receiver operating characteristic analysis. RESULTS: Cement penetration exceeding
      a mean of 1.1 mm or with a maximum of 5.6 mm exclusively categorized all BULK
      bone failure specimens. Failure strength of BULK failure specimens increased with
      bone mineral density (R2 = 0.67, P < .001) but was independent of the cement
      morphology parameters. CONCLUSION: To maximize fixation strength, a mean cement
      penetration depth of at least 1.1 mm should be achieved during tibial tray
      cementing.

PMID- 27687809
TI  - Management of Vancouver B2 and B3 Periprosthetic Proximal Femoral Fractures by
      Distal Locking Femoral Stem (Cannulok) in Patients 75 Years and Older.
AB  - BACKGROUND: Periprosthetic fracture following total hip arthroplasty is a
      significant problem faced by hip surgeons, and its management in elderly patients
      remains a considerable challenge. METHODS: We retrospectively reviewed 28
      Vancouver B2 and B3 periprosthetic femoral fractures (PFF) treated with revision
      of the femoral stems by distally locked, hydroxyapatite-coated uncemented stems
      (Cannulok). Patients were aged 75 years or older at the time of surgery. RESULTS:
      The mean follow-up was 44.6 months (range, 24-102). The mean postoperative Oxford
      hip score was 30.1 (range, 10-46). The rate of fracture union was 95.8%, and the
      survivorship of the stem was 100% at the end of follow-up. CONCLUSION: The
      management of PFF in elderly is associated with increased postoperative morbidity
      and mortality. The use of a distally locked, hydroxyapatite-coated femoral stem
      is a valid option for the treatment of PFF to achieve fracture union with a low
      rate of revision.

PMID- 27687810
TI  - Bone Remodeling in Acetabular Reconstruction Using a Kerboull-Type Reinforcement
      Device and Structural Bone-Grafting in Total Hip Arthroplasty.
AB  - BACKGROUND: The purpose of this study was to identify the long-term durability of
      the Kerboull-type reinforcement device (KT plate) in acetabular reconstruction
      for massive bone defects, assessing the remodeling of structural bone grafts.
      METHODS: This study retrospectively evaluated 106 hips that underwent acetabular
      reconstruction using a KT plate between November 2000 and December 2010. Thirty
      eight primary total hip arthoplasties (THAs) and 68 revised THAs were performed,
      and the mean duration of clinical follow-up was 8 years (5-14 years). Regarding
      reconstructing the acetabular bone defects, autografts were used in 37 hips,
      allografts in 68 hips, and A-W glass ceramics in 2 hips. RESULTS: One hip
      exhibited radiological migration and no revision for aseptic loosening. The mean
      Merle d'Aubigne Clinical Score improved from 7.5 points (4-12 points)
      preoperatively to 10.9 points (9-18 points) at the last follow-up. The Kaplan
      Meier survival rate for radiological migration of primary and revised THAs at 10
      years was 100% and 97% (95% confidence interval: 96%-100%), respectively. Bone
      remodeling was evaluated using the radiological demarcation at the bone-to-bone
      interface, and an improvement of 100% in primary THAs and 94% in revised THAs was
      observed. CONCLUSION: For massive bone defects, acetabular reconstruction using
      the KT plate with a structural bone grafting can yield successful results.

PMID- 27687813
TI  - Recognizing "Bella Swan" and "Hermione Granger": No Own-Race Advantage in
      Recognizing Photos of Famous Faces.
AB  - We investigated recognition of familiar and unfamiliar own- and other-race faces
      across natural variability in appearance. Participants sorted 20 photographs of
      each of two identities into piles such that each pile contained all photographs
      of a single identity. The other-race effect was limited to unfamiliar faces. When
      faces were unfamiliar, participants perceived more identities when sorting other
      race races; when faces were familiar, participants made two piles for both own-
      and other-race faces. Our work calls for rethinking the concept of the other-race
      effect.

PMID- 27687812
TI  - Self-Ratings of Olfactory Performance and Odor Annoyance Are Associated With the
      Affective Impact of Odor, but Not With Smell Test Results.
AB  - Our aim was to explore factors potentially associated with subjective (self
      rated) and objective (measured using the Sniffin' Sticks Extended test) olfactory
      performance in the general population without olfactory disorders. We studied
      associations between olfactory performance and how important odors were in
      determining liking for new places, things, and people (measured using the
      Affective Impact of Odor scale) and the average annoyance caused by odors in 117
      adults (83 women, 34 men; age 18-69 years, mean age 32 years). In a subset of 44
      participants, we also studied associations between olfactory performance and
      spice odor identification task scores (14 odors) and the number of herbs and
      spices consumed. Self-rated olfactory acuity and odor-related annoyance were
      associated with the Affective Impact of Odor scores, but neither correlated with
      the smell test results. Instead, the number of spices consumed correlated with
      spice odor identification score ( r = .50) and the identification (but not
      threshold nor discrimination) subscore of the Sniffin' Sticks test ( r = .49).
      Our results suggest that a tendency to perceive odors in affective terms may be
      associated with overestimation of olfactory abilities and that recurrent exposure
      to a large variety of spice odors may improve performance on odor identification.

PMID- 27687811
TI  - Dyslipidemia: Obese or Not Obese-That Is Not the Question.
AB  - PURPOSE OF REVIEW: Purpose of review: It is becoming increasingly clear that some
      obese individuals do not develop dyslipidemia and instead remain healthy, while
      some normal weight individuals become dyslipidemic and unhealthy. RECENT
      FINDINGS: The present review examines the similarities and differences between
      healthy and unhealthy individuals with and without obesity and discusses putative
      underlying mechanisms of dyslipidemia. The presence of dyslipidemia and
      compromised metabolic health in both lean and obese individuals suggests that the
      obese phenotype per se does not represent a main independent risk factor for the
      development of dyslipidemia and that dyslipidemia, rather than obesity, may be
      the driver of metabolic diseases. Notably, adipose tissue dysfunction and ectopic
      lipid deposition, in particular in the liver, seems a common trait of unhealthy
      individuals.

PMID- 27687815
TI  - Capecitabine and Oxaliplatin Prior and Concurrent to Preoperative Pelvic
      Radiotherapy in Patients With Locally Advanced Rectal Cancer: Long-Term Outcome.
AB  - BACKGROUND: The risk/benefit ratio of any treatment can only be fully assessed if
      long-term results of both efficacy and toxicity are taken into account. Whereas
      the combined modality treatment of locally advanced rectal cancer (LARC) has
      considerably improved prognosis, particularly with regard to local control, long
      term results-including patient-reported outcomes-are underreported. PATIENTS AND
      METHODS: Patients with LARC treated within a multicenter single-arm phase II
      study were prospectively assessed for at least 5 years after surgery. Study
      treatment consisted of capecitabine and oxaliplatin prior and concurrent to
      preoperative pelvic radiotherapy followed by total mesorectal excision.
      Progression-free survival time (first endpoint), overall survival time, and
      pattern of relapse were analyzed in the whole study population and in pre-planned
      exploratory subgroups. Patient-reported outcomes, including overall satisfaction
      with bowel, stoma, and urinary function, were assessed in 6-month intervals.
      RESULTS: Five-year progression-free and overall survival rate was 61% (95%
      confidence interval [CI], 46%-73%) and 78% (95% CI, 63%-87%), respectively.
      Distant to local recurrence rate was 3:1, with only 8% of patients relapsing
      locally. Main predictors for recurrence in univariate analyses were tumor
      downstaging (hazard ratio, 0.16; 95% CI, 0.05-0.56; P = .0011) and nodal
      downstaging (hazard ratio, 0.17; 95% CI, 0.06-0.52; P = .0005). The self-reported
      burden of symptoms related to bowel function was high in up to one-third of
      patients. A total of 28% of patients were dissatisfied with their urinary, bowel,
      or stoma function for at least 1 observation period. CONCLUSION: Combined
      modality treatment of LARC results in a high and durable local disease control
      rate, especially in patients with tumor and/or nodal downstaging, at the cost of
      relevant long-term toxicity. Long-term care is required for a proportion of
      patients with poor gastrointestinal and/or urinary function after multimodality
      therapy. Reporting of long-term follow-up, including patient-recorded outcomes
      should be mandatory for future trials in LARC.

PMID- 27687816
TI  - Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms
      and a new theory on seizure development.
AB  - The WAG/Rij rat model has recently gathered attention as a suitable animal model
      of absence epileptogenesis. This latter term has a broad definition encompassing
      any possible cause that determines the development of spontaneous seizures;
      however, most of, if not all, preclinical knowledge on epileptogenesis is
      confined to the study of post-brain insult models such as traumatic brain injury
      or post-status epilepticus models. WAG/Rij rats, but also synapsin 2 knockout,
      Kv7 current-deficient mice represent the first examples of genetic models where
      an efficacious antiepileptogenic treatment (ethosuximide) was started before
      seizure onset. In this review, we have critically reconsidered all articles
      published regarding WAG/Rij rats, from the perspective that the period before SWD
      onset is considered as the latent period. In our new theory on seizure
      development, it is proposed that genes might be considered as the initial
      'insult' responsible for all plastic changes underpinning the development of
      spontaneous seizures. According to this idea, in WAG/Rij rats, genetic
      predisposition would lead to the development of abnormal bilateral cortical
      epileptic foci, which would then non-genetically stimulate the rest of the brain
      to rearrange networks in order to phenotypically develop seizures similarly to
      what happens during electrical kindling.

PMID- 27687814
TI  - The Olfactory Mosaic: Bringing an Olfactory Network Together for Odor Perception.
AB  - Olfactory perception and its underlying neural mechanisms are not fixed, but
      rather vary over time, dependent on various parameters such as state, task, or
      learning experience. In olfaction, one of the primary sensory areas beyond the
      olfactory bulb is the piriform cortex. Due to an increasing number of functions
      attributed to the piriform cortex, it has been argued to be an associative cortex
      rather than a simple primary sensory cortex. In fact, the piriform cortex plays a
      key role in creating olfactory percepts, helping to form configural odor objects
      from the molecular features extracted in the nose. Moreover, its dynamic
      interactions with other olfactory and nonolfactory areas are also critical in
      shaping the olfactory percept and resulting behavioral responses. In this brief
      review, we will describe the key role of the piriform cortex in the larger
      olfactory perceptual network, some of the many actors of this network, and the
      importance of the dynamic interactions among the piriform-trans-thalamic and
      limbic pathways.

PMID- 27687817
TI  - The link between autoimmune diseases and obsessive-compulsive and tic disorders:
      A systematic review.
AB  - Immunological factors are increasingly recognized as being important in a range
      of neuropsychiatric disorders. We aimed to summarize the disperse and often
      conflicting literature on the potential association between autoimmune diseases
      (ADs) and obsessive-compulsive disorder (OCD) and tic disorders. We searched
      PubMed, EMBASE, and PsycINFO for original studies evaluating the relationship
      between ADs and OCD/tic disorders until July, 13th 2016. Seventy-four studies met
      inclusion criteria. Overall, the studies were of limited methodological quality.
      Rates of OCD were higher in rheumatic fever patients who were also affected by
      its neurological manifestation, Sydenham's chorea. The literature on other ADs
      was scarce and the findings inconclusive. Few studies examined the association
      between ADs and tic disorders. A handful of family studies reported elevated
      rates of ADs in first-degree relatives of individuals with OCD/tic disorders, and
      vice versa, potentially suggesting shared genetic and/or environmental
      mechanisms. In conclusion, at present, there is modest evidence for a possible
      association and familial co-aggregation between ADs and OCD/tic disorders. We
      offer some suggestions for future research.

PMID- 27687818
TI  - Feelings of shame, embarrassment and guilt and their neural correlates: A
      systematic review.
AB  - This systematic review aimed to provide a comprehensive summary of the current
      literature on the neurobiological underpinnings of the experience of the negative
      moral emotions: shame, embarrassment and guilt. PsycINFO, PubMed and MEDLINE were
      used to identify existing studies. Twenty-one functional and structural magnetic
      resonance imaging and positron emission tomography studies were reviewed.
      Although studies differed considerably in methodology, their findings highlight
      both shared and distinct patterns of brain structure/function associated with
      these emotions. Shame was more likely to be associated with activity in the
      dorsolateral prefrontal cortex, posterior cingulate cortex and sensorimotor
      cortex; embarrassment was more likely to be associated with activity in the
      ventrolateral prefrontal cortex and amygdala; guilt was more likely to be
      associated with activity in ventral anterior cingulate cortex, posterior temporal
      regions and the precuneus. Although results point to some common and some
      distinct neural underpinnings of these emotions, further research is required to
      replicate findings.

PMID- 27687819
TI  - Re: Prognostic Significance of Percentage and Architectural Types of Contemporary
      Gleason Pattern 4 Prostate Cancer in Radical Prostatectomy.

PMID- 27687820
TI  - Solifenacin in Children and Adolescents with Overactive Bladder: Results of a
      Phase 3 Randomised Clinical Trial.
AB  - BACKGROUND: Solifenacin, an effective, well-tolerated treatment for adult
      overactive bladder (OAB) symptoms, has not been evaluated in placebo-controlled
      paediatric clinical trials. OBJECTIVES: To evaluate the efficacy and safety of
      once-daily oral solifenacin suspension in OAB patients aged 5-<12 yr (children)
      and 12-<18 yr (adolescents). DESIGN, SETTING, AND PARTICIPANTS: The study
      involved a 4-wk urotherapy run-in followed by 1:1 randomisation to 12-wk double
      blind solifenacin or placebo treatment alongside urotherapy. INTERVENTION:
      Solifenacin paediatric equivalent doses (PEDs) of adult doses: 2.5mg, 5mg, 7.5mg,
      and 10mg. The starting dose was PED 5mg; all patients were titrated to an optimum
      dose at 3-wk intervals over 9 wk, resulting in >=3 wk at the optimum dose before
      end of treatment (EoT). OUTCOME MEASUREMENTS AND STATISTICS: Superiority of
      solifenacin versus placebo in change from baseline to EoT for mean volume
      voided/micturition (MVV, primary endpoint); daytime maximum volume
      voided/micturition (DMaxVV); incontinence episodes (mean/24h); mean number of
      incontinence-free days or nights/7 d; micturition frequency; and Micturition
      frequency adjusted for baseline total voided volume (VTB) as an exploratory
      parameter). Efficacy parameters were analysed using analysis of covariance.
      Safety parameters (treatment-emergent adverse events, serious adverse events,
      laboratory variables, vital signs, electrocardiogram, postvoid residual volume)
      are summarised using descriptive statistics. RESULTS AND LIMITATIONS: In
      children, solifenacin was superior to placebo in terms of the change from
      baseline to EoT for MVV (solifenacin-placebo difference 12.1ml, 95% confidence
      interval [CI] 0.2-24.0; p=0.046), DMaxVV (difference in adjusted mean change from
      baseline for solifenacin-placebo 31.9ml, 95% CI 4.3-59.5; p=0.024), VTB-adjusted
      micturition frequency (p=0.028). Other endpoints were not significantly
      different. Solifenacin was well tolerated. For adolescents, it was not possible
      to draw firm efficacy conclusions because of the low numbers recruited.
      CONCLUSIONS: Once-daily solifenacin oral suspension in children with OAB was
      superior to placebo for MVV (primary efficacy endpoint) and was well tolerated.
      PATIENT SUMMARY: In this 12-wk study, a once-daily oral suspension of solifenacin
      in children aged 5-<12 yr with overactive bladder was superior to placebo in
      increasing mean volume voided/micturition, the primary efficacy variable in the
      study. Solifenacin was well tolerated, with a low incidence of dry mouth and
      constipation. This study is registered at ClinicalTrials.gov as NCT01565707.

PMID- 27687821
TI  - Systematic Review of the Performance of Noninvasive Tests in Diagnosing Bladder
      Outlet Obstruction in Men with Lower Urinary Tract Symptoms.
AB  - CONTEXT: Several noninvasive tests have been developed for diagnosing bladder
      outlet obstruction (BOO) in men to avoid the burden and morbidity associated with
      invasive urodynamics. The diagnostic accuracy of these tests, however, remains
      uncertain. OBJECTIVE: To systematically review available evidence regarding the
      diagnostic accuracy of noninvasive tests in diagnosing BOO in men with lower
      urinary tract symptoms (LUTS) using a pressure-flow study as the reference
      standard. EVIDENCE ACQUISITION: The EMBASE, MEDLINE, Cochrane Database of
      Systematic Reviews, Cochrane Central, Google Scholar, and WHO International
      Clinical Trials Registry Platform Search Portal databases were searched up to May
      18, 2016. All studies reporting diagnostic accuracy for noninvasive tests for BOO
      or detrusor underactivity in men with LUTS compared to pressure-flow studies were
      included. Two reviewers independently screened all articles, searched the
      reference lists of retrieved articles, and performed the data extraction. The
      quality of evidence and risk of bias were assessed using the QUADAS-2 tool.
      EVIDENCE SYNTHESIS: The search yielded 2774 potentially relevant reports. After
      screening titles and abstracts, 53 reports were retrieved for full-text
      screening, of which 42 (recruiting a total of 4444 patients) were eligible.
      Overall, the results were predominantly based on findings from nonrandomised
      experimental studies and, within the limits of such study designs, the quality of
      evidence was typically moderate across the literature. Differences in noninvasive
      test threshold values and variations in the urodynamic definition of BOO between
      studies limited the comparability of the data. Detrusor wall thickness (median
      sensitivity 82%, specificity 92%), near-infrared spectroscopy (median sensitivity
      85%, specificity 87%), and the penile cuff test (median sensitivity 88%,
      specificity 75%) were all found to have high sensitivity and specificity in
      diagnosing BOO. Uroflowmetry with a maximum flow rate of <10ml/s was reported to
      have lower median sensitivity and specificity of 68% and 70%, respectively.
      Intravesical prostatic protrusion of >10mm was reported to have similar
      diagnostic accuracy, with median sensitivity of 68% and specificity of 75%.
      CONCLUSIONS: According to the literature, a number of noninvasive tests have high
      sensitivity and specificity in diagnosing BOO in men. However, although the
      majority of studies have a low overall risk of bias, the available evidence is
      limited by heterogeneity. While several tests have shown promising results
      regarding noninvasive assessment of BOO, invasive urodynamics remain the gold
      standard. PATIENT SUMMARY: Urodynamics is an accurate but potentially
      uncomfortable test for patients in diagnosing bladder problems such as
      obstruction. We performed a thorough and comprehensive review of the literature
      to determine if there were less uncomfortable but equally effective alternatives
      to urodynamics for diagnosing bladder problems. We found that some simple tests
      appear to be promising, although they are not as accurate. Further research is
      needed before these tests are routinely used in place of urodynamics.

PMID- 27687822
TI  - Re: Thomas Seisen, Benoit Peyronnet, Jose Luis Dominguez-Escrig, et al. Oncologic
      Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper
      Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-muscle Invasive
      Bladder Cancer Guidelines Panel. Eur Urol 2016;70:1052-68: Preoperative Bladder
      Cancer History and Chronic Kidney Disease Are Associated with Occult Renal Pelvis
      Cancer in Preoperative Solitary Ureteral Cancer.

PMID- 27687824
TI  - Dysphagia - Results from multivariable predictive modelling on aspiration from a
      subset of the ARTSCAN trial.
AB  - PURPOSE: To establish predictive models for late objective aspiration and late
      patient-reported choking based on dose-volume parameters and baseline patient and
      treatment characteristics, for patients with head and neck cancer undergoing
      definitive radiotherapy (RT). The impact of electively treated volume on late
      aspiration was also investigated. METHODS AND MATERIAL: This prospective cohort
      is a subsample of 124 survivors from the ARTSCAN study. Late aspiration was
      identified with videofluoroscopy, at a minimum of 25months after the start of RT.
      Patient-reported choking was analysed at 12 and 60months post RT using the EORTC
      Quality of Life Module for Head and Neck Cancer 35. Univariable and multivariable
      analyses were performed to describe the association between clinical factors and
      dose-volume descriptors for organs at risk (OARs) and late dysphagia. RESULTS:
      Aspiration was found in 47% of the eligible patients. Mean dose to the middle
      pharyngeal constrictor (MPC), neck dissection post RT and age at randomisation in
      ARTSCAN were associated to late aspiration. Mean dose to the superior pharyngeal
      constrictor (SPC) and swallowing complaints at baseline were associated to
      patient reported choking at both time-points. CONCLUSIONS: Three separate risk
      groups for late aspiration, and two risk groups for late patient-reported choking
      were identified based on number of risk factors. The size of the electively
      treated volume could be used as a surrogate for individual OARs predicting late
      aspiration.

PMID- 27687826
TI  - An epistatic explanation.
AB  - Interactions between two gene variants that rarely cause midline craniosynostosis
      on their own make the development of the disorder a certainty.

PMID- 27687823
TI  - Quality of life and disability: can they be improved by active postoperative
      rehabilitation after spinal fusion surgery in patients with spondylolisthesis? A
      randomised controlled trial with 12-month follow-up.
AB  - PURPOSE: The aim of the study was to investigate the effectiveness of the
      postoperative 12-month exercise program compared to usual care on disability and
      health-related quality of life (HRQoL) in patients after lumbar spine fusion
      surgery (LSF). METHODS: Altogether, 98 patients with isthmic (31) or degenerative
      (67) spondylolisthesis were randomised to exercise therapy group (EG) (n = 48) or
      usual care group (UCG) (n = 50) 3 months after LSF. EG patients had home-based
      progressive strength and aerobic training program for 12 months. UCG patients
      received only oral and written instructions of exercises. Oswestry Disability
      Index (ODI) and HRQoL (RAND-36) were evaluated at the time of randomization, at
      the end of the intervention and 1 year after intervention. RESULTS: The mean ODI
      score decreased from 24 (12) to 18 (14) in the EG and from 18 (12) to 13 (11) in
      the UCG during intervention (between-groups p = 0.69). At 1-year follow-up, 25 %
      of the EG and 28 % of the UCG had an ODI score >=20. No between-group differences
      in HRQoL change were found at any time point. The mean (95 % CI) physical
      functioning dimension of the HRQoL improved by 10.0 (4.6-15.3) in the EG and by
      7.8 (2.5-13.0) in the UCG. In addition, the role physical score improved by 20.0
      (7.7-32.3) in the EG and by 16.4 (4.4-28.4) in the UCG during the intervention.
      CONCLUSIONS: The exercise intervention did not have an impact on disability or
      HRQoL beyond the improvement achieved by usual care. However, disability remained
      at least moderate in considerable proportion of patients.

PMID- 27687825
TI  - Fluorescent quantitative PCR detection of Mycobacterium tuberculosis in tissue
      sections from granulomatous lesions retrieved using EDTA.
AB  - AIMS: This study aimed to use EDTA to retrieve paraffin-embedded tissue sections
      of inflammatory granulomatous lesions and increase the detection rate of
      tuberculosis (TB)/non-tuberculous mycobacteria. Due to the influence of chemical
      reagents during the fixation process, the amplification of fluorescent
      quantitative PCR was blocked after DNA extraction, and the results were not
      ideal. METHODS: Special staining technologies (acid-fast and Auramine O) and
      fluorescent quantitative PCR were used to detect TB/non-tuberculous mycobacteria
      in 125 cases of inflammatory granulomatous lesions in paraffin-embedded tissue
      sections with and without EDTA retrieval. RESULTS: In 125 cases of inflammatory
      granulomatous lesions, 75 cases (60%) were positive for mycobacteria using
      fluorescent quantitative PCR without EDTA retrieval, of which 74 cases (59.2%)
      were detected with TB mycobacteria and 1 case (0.8%) with non-tuberculous
      mycobacteria. The average cycle threshold value of positive specimens ranged from
      29 to 32 (30.5). However, 88 cases (70.4%) were positive for mycobacteria using
      fluorescent quantitative PCR with EDTA retrieval, of which 83 cases (66.4%) were
      detected with TB mycobacteria and 5 cases (4%) with non-tuberculous mycobacteria.
      The average Ct value of positive specimens ranged from 27 to 30 (28.0).
      Statistical differences were found between the two groups (p<0.05; p<0.01).
      CONCLUSIONS: This study showed that compared with special staining technologies
      (acid-fast and Auramine O) and molecular pathology detection, fluorescent
      quantitative PCR with EDTA retrieval could greatly improve the detection rate of
      TB/non-tuberculous mycobacteria and increase the sensitivity of the fluorescent
      quantitative PCR.

PMID- 27687827
TI  - Esophageal stricture after endoscopic submucosal dissection treated successfully
      by temporary stent placement.
AB  - The growing use of endoscopic submucosal dissection (ESD) has enabled the highly
      curative treatment of early esophageal cancer. The circumferential extent of the
      tumor is reportedly related to the frequency of post-treatment stricture, with
      postoperative esophageal stricture reported to occur frequently when the post
      resection mucosal defect exceeds 75 % of the esophageal luminal circumference. In
      some clinical cases, locally injected or orally administered steroids aimed at
      preventing post-treatment stricture fail to prevent re-stricture. Only two prior
      reports have investigated temporary stent placement for stricture after ESD for
      early esophageal cancer, and consensus is lacking on the appropriate duration and
      timing of stent placement. Here, we report our experience with a case of
      stricture after ESD for early esophageal cancer, in which temporary stent
      placement was effective for releasing the stricture for at least 6 months.

PMID- 27687828
TI  - Postmortem computed tomography findings in suicide victims.
AB  - Suicide is the eighth cause of mortality in France and the leading cause in
      people aged between 25 and 34 years. The most common methods of suicide are
      hanging, self-poisoning with medicines and firearms. Postmortem computed
      tomography (CT) is a useful adjunct to autopsy to confirm suicide and exclude
      other causes of death. At autopsy, fractures of the hyoid bone or thyroid
      cartilage, or both, are found in more than 50% of suicidal hangings. Cervical
      vertebra fractures are rare and only seen in suicide victims jumping from a great
      height. Three-dimensional reconstructions from CT data are useful to visualize
      the ligature mark on the neck. In suicides by firearm, postmortem CT shows entry
      and exit wounds, parenchymal lesions along the bullet path, as well as
      projectiles in case of penetrating trauma. However, in the chest and abdomen it
      is more difficult to identify the path of the projectile. Postmortem CT also
      shows specific features of suicide by drowning or stabbing, but its use is
      limited in cases of self-poisoning. The use of postmortem CT is also limited by
      decomposition and change of body position. This article presents the imaging
      features seen on postmortem CT according to the method of suicide.

PMID- 27687829
TI  - Contrast-enhanced spectral mammography (CESM) versus breast magnetic resonance
      imaging (MRI): A retrospective comparison in 66 breast lesions.
AB  - OBJECTIVE: The purpose of this study was to retrospectively compare the
      diagnostic performance of contrast-enhanced spectral mammography (CESM) with that
      of breast magnetic resonance imaging (BMRI) in breast cancer detection using
      parameters, including sensitivity, positive predictive value (PPV), lesion size,
      morphology, lesion and background enhancement, and examination time. MATERIALS
      AND METHODS: A total of 48 women (mean age, 56years+/-10.6 [SD]) with breast
      lesions detected between October 2012 and March 2014 were included. Both CESM and
      BMRI were performed for each patient within 30 days. The enhancement intensity of
      lesions and breast background parenchyma was subjectively assessed for both
      modalities and was quantified for comparison. Statistical significance was
      analyzed using paired t-test for mean size of index lesions in all malignant
      breasts (an index lesion defined as the largest lesion in each breast), and a
      mean score of enhancement intensity for index lesions and breast background. PPV,
      sensitivity, and accuracy were calculated for both CESM and BMRI. The average
      duration time of CESM and MRI examinations was also compared. RESULTS: A total of
      66 lesions were identified, including 62 malignant and 4 benign lesions. Both
      CESM and BMRI demonstrated a sensitivity of 100% for detection of breast cancer.
      There was no statistically significant difference between the mean size of index
      lesions (P=0.108). The enhancement intensity of breast background was
      significantly lower for CESM than for BMRI (P<0.01). The mean score of
      enhancement intensity of index lesions on CESM was significantly less than that
      for BMRI (P<0.01). The smallest lesion that was detected by both modalities
      measured 4mm. CESM had a higher PPV than BMRI (P>0.05). The average examination
      time for CESM was significantly shorter than that of BMRI (P<0.01). CONCLUSION:
      CESM has similar sensitivity than BMRI in breast cancer detection, with higher
      PPV and less background enhancement. CESM is associate with significantly shorter
      exam time thus a more accessible alternative to BMRI, and has the potential to
      play an important tool in breast cancer detection and staging.

PMID- 27687830
TI  - Normal postoperative appearances of lung cancer.
AB  - The major lung resections are the pneumonectomies and lobectomies. The sublobar
      resections are segmentectomies and wedge resections. These are performed either
      through open surgery through a thoracotomy or by video-assisted mini-invasive
      surgery for lobectomies and sublobar resections. Understanding the procedures
      involved allows the normal postoperative appearances to be interpreted and these
      normal anatomical changes to be distinguished from potential postoperative
      complications. Surgery results in a more or less extensive physiological
      adaptation of the chest cavity depending on the lung volume, which has been
      resected. This adaptation evolves during the initial months postoperatively.
      Chest radiography and computed tomography can show narrowing of the intercostal
      spaces, a rise of the diaphragm and shift of the mediastinum on the side
      concerned following major resections.

PMID- 27687831
TI  - Correlation between apparent diffusion coefficient value on diffusion-weighted MR
      imaging and Gleason score in prostate cancer.
AB  - OBJECTIVES: To investigate whether diffusion-weighted imaging (DWI) apparent
      diffusion coefficient (ADC) correlates with prostate cancer aggressiveness and
      further to compare the diagnostic performance of ADC and normalized ADC (nADC:
      normalized to non-tumor tissue). PATIENTS AND METHODS: Thirty pre-treatment
      patients (mean age, 69years; range: 59-78years) with prostate cancer underwent
      magnetic resonance imaging (MRI) examination, including DWI with three b values:
      50, 400, and 800s/mm2. Both ADC and nADC were correlated with the Gleason score
      obtained through transrectal ultrasound-guided biopsy. RESULTS: The tumor minimum
      ADC (ADCmin: the lowest ADC value within tumor) had an inverse correlation with
      the Gleason score (r=-0.43, P<0.05), and it was lower in patients with Gleason
      score 3+4 than in those with Gleason score 3+3 (0.54+/-0.11*103mm2/s vs. 0.64+/
      0.12*10-3mm2/s, P<0.05). Both the nADCmin and nADCmean correlated with the
      Gleason score (r=-0.52 and r=-0.55, P<0.01; respectively), and they were lower in
      patients with Gleason score 3+4 than those with Gleason score 3+3 (P<0.01;
      respectively). Receiver operating characteristic (ROC) analysis showed that the
      area under the ROC curve was 0.765, 0.818, or 0.833 for the ADCmin, nADCmin, or
      nADCmean; respectively, in differentiating between Gleason score 3+4 and 3+3
      tumors. CONCLUSION: Tumor ADCmin, nADCmin, and nADCmean are useful markers to
      predict the aggressiveness of prostate cancer.

PMID- 27687832
TI  - A single enhanced phase is sufficient for the initial computed tomography
      evaluation of retroperitoneal tumors in children.
AB  - PURPOSE: The goal of this study was to evaluate the incremental value of
      unenhanced phase in the initial evaluation of retroperitoneal tumors in children
      by comparison with an enhanced phase alone using computed tomography (CT).
      MATERIALS AND METHODS: A total of 53 patients (26 girls, 27 boys) with a total of
      53 tumors who had CT examination of the abdomen and pelvis for the initial
      assessment of retroperitoneal tumor were retrospectively included. All CT
      examinations were obtained with an unenhanced set of CT images and a set of CT
      images obtained after intravenous administration of iodinated contrast material.
      One junior and one senior radiologist independently evaluated the two sets in two
      separate reading sessions. CT images were analyzed for tumor calcifications,
      tumor location, vascular encasement, local invasion and tumor content. RESULTS:
      Calcifications were present in 24/53 tumors (45%). On the enhanced set, the
      senior radiologist was able to detect calcifications in 22/24 tumors (92%) and
      the junior radiologist in 20/24 tumors (83%), yielding sensitivities of 92% and
      83%, and specificities of 96.5% and 100%, respectively. Inter-observer agreement
      was excellent (Kappa=0.89). Tumor location was correctly determined by the senior
      radiologist in 53/53 tumors (100%) and 37/53 tumors (70%) by the junior
      radiologist. Using the unenhanced set, the senior radiologist was able to assess
      vascular encasement in 26/53 tumors (49%) against 21/53 (39%) for the junior
      radiologist. For tumor content, agreement between the enhanced and combined
      unenhanced and enhanced CT was 77% for both radiologists. CONCLUSION: Enhanced CT
      performs as well as unenhanced CT for evidencing calcifications and is therefore
      sufficient for the initial assessment of retroperitoneal tumor in children.

PMID- 27687833
TI  - CT imaging in pre-therapeutic assessment of lung cancer.
AB  - Lung cancer, the most frequent cancer worldwide, is the fourth most frequent
      cancer in France, with an overall 5-year survival rate of about 15%, directly
      correlated to the stage of disease at the time of diagnosis and its treatment.
      The objective of this article is to describe the role, contributions and pitfalls
      of computed tomography (CT) in clinical TNM staging, primarily to identify
      patients eligible for curative surgery. TNM staging criteria, last updated in
      2009, are discussed along with the new proposals for the 8th edition to be
      published late 2016. The most crucial CT features for pre-therapy assessment are
      highlighted.

PMID- 27687834
TI  - What an exciting time it is: a pictorial essay of Doppler sonography.

PMID- 27687835
TI  - Editor's note.

PMID- 27687837
TI  - Invited Commentary: Administrative vs Clinical Data: The Struggle Continues.

PMID- 27687838
TI  - Toward External Validation and Routine Clinical Use of the American College of
      Surgeons NSQIP Surgical Risk Calculator.

PMID- 27687839
TI  - Considerations in Releasing Equations for the American College of Surgeons NSQIP
      Surgical Risk Calculator: In Reply to Wanderer and Ehrenfeld.

PMID- 27687840
TI  - Mitigating Surgeon Burnout.

PMID- 27687841
TI  - Alkaline Phosphatase Supplementation for Gut Barrier Protection.

PMID- 27687842
TI  - Patients with Uniform Diseases and Uniform Surgical Procedures May Help Define
      the Safety of Topical Hemostatic Agents.

PMID- 27687843
TI  - Liver Condition and Resection: In reply to Toro and colleagues.

PMID- 27687845
TI  - RNA interference in the Colorado potato beetle, Leptinotarsa decemlineata:
      Identification of key contributors.
AB  - RNA interference (RNAi) is a useful reverse genetics tool for investigation of
      gene function as well as for practical applications in many fields including
      medicine and agriculture. RNAi works very well in coleopteran insects including
      the Colorado potato beetle (CPB), Leptinotarsa decemlineata. We used a cell line
      (Lepd-SL1) developed from CPB to identify genes that play key roles in RNAi. We
      screened 50 genes with potential functions in RNAi by exposing Lepd-SL1 cells to
      dsRNA targeting one of the potential RNAi pathway genes followed by incubation
      with dsRNA targeting inhibitor of apoptosis (IAP, silencing of this gene induces
      apoptosis). Out of 50 genes tested, silencing of 29 genes showed an effect on
      RNAi. Silencing of five genes (Argonaute-1, Argonaute-2a, Argonaute-2b, Aubergine
      and V-ATPase 16 kDa subunit 1, Vha16) blocked RNAi suggesting that these genes
      are essential for functioning of RNAi in Lepd-SL1 cells. Interestingly, Argonaute
      1 and Aubergine which are known to function in miRNA and piRNA pathways
      respectively are also critical to siRNA pathway. Using 32P labeled dsRNA, we
      showed that these miRNA and piRNA Argonautes but not Argonaute-2 are required for
      processing of dsRNA to siRNA. Transfection of pIZT/V5 constructs containing these
      five genes into Sf9 cells (the cells where RNAi does not work well) showed that
      expression of all genes tested, except the Argonaute-2a, improved RNAi in these
      cells. Results from Vha16 gene silencing and bafilomycin-A1 treatment suggest
      that endosomal escape plays an important role in dsRNA-mediated RNAi in Lepd-SL1
      cells.

PMID- 27687846
TI  - Gossypol toxicity and detoxification in Helicoverpa armigera and Heliothis
      virescens.
AB  - Gossypol is a polyphenolic secondary metabolite produced by cotton plants, which
      is toxic to many organisms. Gossypol's aldehyde groups are especially reactive,
      forming Schiff bases with amino acids of proteins and cross-linking them,
      inhibiting enzyme activities and contributing to toxicity. Very little is known
      about gossypol's mode of action and its detoxification in cotton-feeding insects
      that can tolerate certain concentrations of this compound. Here, we tested the
      toxicity of gossypol and a gossypol derivative lacking free aldehyde groups (SB
      gossypol) toward Helicoverpa armigera and Heliothis virescens, two important
      pests on cotton plants. Larval feeding studies with these two species on
      artificial diet supplemented with gossypol or SB-gossypol revealed no detectable
      toxicity of gossypol, when the aldehyde groups were absent. A cytochrome P450
      enzyme, CYP6AE14, is upregulated in H. armigera feeding on gossypol, and has been
      claimed to directly detoxify gossypol. However, using in vitro assays with
      heterologously expressed CYP6AE14, no metabolites of gossypol were detected, and
      further studies suggest that gossypol is not a direct substrate of CYP6AE14.
      Furthermore, larvae feeding on many other plant toxins also upregulate CYP6AE14.
      Our data demonstrate that the aldehyde groups are critical for the toxicity of
      gossypol when ingested by H. armigera and H. virescens larvae, and suggest that
      CYP6AE14 is not directly involved in gossypol metabolism, but may play a role in
      the general stress response of H. armigera larvae toward plant toxins.

PMID- 27687847
TI  - Hospital Volume and Outcomes of Robot-Assisted Lobectomies.
AB  - BACKGROUND: The positive impact of hospital operative volume on outcomes
      following video-assisted thoracoscopic surgery has been established. The goal of
      this study was to determine whether or not this volume/outcome relationship
      translates to robot-assisted thoracoscopic surgery (RobATS) lobectomy. METHODS:
      Patients who underwent RobATS lobectomy were identified between 2008 and 2013 in
      the Healthcare Cost and Utilization Project National Inpatient Sample database.
      Hospital volume, as well as demographic, clinical, and health-care system-related
      factors were selected as potential predictors of outcomes. Outcome variables
      included length of stay (LOS), inpatient mortality, and complications. Hospitals
      were designated by quartiles according to annual case volume, with very low
      volume defined as the first quartile and high-volume defined as the fourth
      quartile. Regression analyses were used to identify independent predictors of the
      outcomes of interest. RESULTS: A total of 8,253 RobATS lobectomies were
      identified. Compared with very low-volume centers, patients at high-volume
      hospitals had a shorter mean LOS (5.8 vs 6.5 days; P = .001) and decreased
      mortality rate (0.5% vs 1.9%; P < .001) but more complications (28.1% vs 27.6%; P
      = .025). In multivariable analysis, high hospital volume was prognostic for
      decreased mortality (OR, 0.134; P< .001) and shorter LOS (0.2 days; SE, 0.05;
      P<.001). Hospital volume was not prognostic for any complications, including
      pulmonary, cardiovascular, intraoperative, or infectious complications.
      CONCLUSIONS: Undergoing lobectomy at high-volume RobATS centers confers favorable
      mortality and LOS outcomes compared with very low-volume centers. In this
      relatively early phase of adoption of RobATS, the long-term clinical impact of
      differences in LOS as well as the lack of clinical impact on the incidence of
      complications remain to be determined more definitively. However, the beneficial
      effect of volume on mortality suggests a need for the careful adoption of this
      promising technology.

PMID- 27687849
TI  - Heroes of peer review: Hyongbum (Henry) Kim.
AB  - Peer reviewers are the unsung heroes of science. We celebrate reviewers through a
      series of interviews with people who have made particularly strong recent
      contributions to Genome Biology as reviewers. The first interview is with
      Hyongbum (Henry) Kim, an Associate Professor at Yonsei University College of
      Medicine in South Korea.

PMID- 27687848
TI  - Association of Sarcoidosis With Increased Risk of VTE: A Population-Based Study,
      1976 to 2013.
AB  - OBJECTIVE: The goal of this study was to investigate the risk of VTE among
      patients with sarcoidosis. METHODS: A cohort of 345 incident cases of sarcoidosis
      and 345 sex- and age-matched comparator subjects in Olmsted County, Minnesota,
      from 1976 to 2013 were identified from the comprehensive medical record linkage
      system. Medical records were reviewed for DVT and pulmonary embolism (PE). The
      cumulative incidence was estimated, adjusted for the competing risk of death. Cox
      proportional hazards models were used to compare the rate of development of these
      events between patients with sarcoidosis and the nonsarcoidosis comparison
      cohort. RESULTS: The prevalence of VTE, DVT, and PE prior to the index date was
      not significantly different between case and comparator subjects. The risk of
      incident VTE adjusted for age, sex, and calendar year was significantly higher
      among patients with sarcoidosis (hazard ratio [HR], 3.04 [95% CI, 1.47-6.29]).
      Significantly elevated risk was observed in both subtypes of VTE, with an HR of
      3.14 (95% CI, 1.32-7.48) for DVT and an HR of 4.29 (95% CI, 1.21-15.23) for PE. A
      sensitivity analysis including only VTE events that occurred at least 6 months
      after the index date adjusted for age, sex, and calendar year revealed somewhat
      lower HRs: VTE, 2.73 (95% CI, 1.30-5.72); DVT, 3.00 (95% CI, 1.25-7.20); and PE,
      3.58 (95% CI, 0.98-13.03). CONCLUSIONS: An increased risk of VTE among patients
      with sarcoidosis was observed in this population-based cohort.

PMID- 27687850
TI  - Helicobacter pylori DNA isolation in the stool: an essential pre-requisite for
      bacterial noninvasive molecular analysis.
AB  - PURPOSE: Real-time polymerase chain reaction (RT-PCR) is a widely used technique
      for bacterial and viral infection diagnosis. Herein, we report our preliminary
      experience in retrieving H. pylori genetic sequences in stools and analyzing
      genotypic clarithromycin resistance by RT-PCR (noninvasive), with the aim of
      comparing this procedure with that performed on biopsy samples (invasive).
      MATERIALS AND METHODS: After 'in vitro' demonstration of H. pylori DNA detection
      from pure and stool-mixed bacteria, 52 consecutive patients at the first
      diagnosis of infection were investigated. DNA was extracted from biopsy tissue
      and stool samples (THD(r) Fecal Test, Italy). RT-PCR was performed to detect 23S
      rRNA encoding bacterial subunit gene and search A2143G, A2142C, A2142G point
      mutations for clarithromycin resistance assessment. RESULTS: RT-PCR showed H.
      pylori positive DNA in all infected patients with full concordance between tissue
      and stool detection (100%). We found A2143G mutation in 10 (19.2%), A2142G in 4
      (7.7%) and A2142C in 5 (9.6%) patients; there was a full agreement between biopsy
      and fecal samples. A2143G was found in all the four A2142G positive cases and in
      three out of the five A2142C positive strains. Overall clarithromycin resistance
      rate in our series was 23%. CONCLUSIONS: Despite the need of confirmation on
      large sample, stool RT-PCR analysis could represent a feasible tool to detect H.
      pylori DNA sequences and antibiotic resistance point mutations. As compared to
      tissue molecular analysis, this technique is noninvasive, with potential
      advantages such as improvement of patient compliance, reduction of diagnostic
      procedure time/cost and improvement of therapeutic outcome.

PMID- 27687852
TI  - Laparoscopic Removal of a Retroperitoneal Hysteroscopic Microinsert Using
      Fluoroscopy.
AB  - Perforation during placement of hysteroscopic microinserts for permanent
      sterilization occurs in approximately .9% to 2.6% of women undergoing the
      procedure. Most of the time perforation results in intraperitoneal placement of
      the hysteroscopic microinsert requiring laparoscopy or laparotomy for removal of
      the device. Herein we present a case of hysteroscopic microinsert perforation
      with subsequent retroperitoneal identification of the device. This is the first
      such case to our knowledge of retroperitoneal identification and retrieval of a
      perforated device that required real-time fluoroscopy during laparoscopy.

PMID- 27687851
TI  - A Randomized Controlled Multicenter US Food and Drug Administration Trial of the
      Safety and Efficacy of the Minerva Endometrial Ablation System: One-Year Follow
      Up Results.
AB  - STUDY OBJECTIVE: To assess the safety and effectiveness of the Minerva
      Endometrial Ablation System for the treatment of heavy menstrual bleeding in
      premenopausal women. DESIGN: Multicenter, randomized, controlled, international
      study (Canadian Task Force classification I). SETTING: Thirteen academic and
      private medical centers. PATIENTS: Premenopausal women (n = 153) suffering from
      heavy menstrual bleeding (PALM-COEIN: E, O). INTERVENTION: Patients were treated
      using the Minerva Endometrial Ablation System or rollerball ablation.
      MEASUREMENTS AND MAIN RESULTS: At 1-year post-treatment, study success (alkaline
      hematin <=80 mL) was observed in 93.1% of Minerva subjects and 80.4% of
      rollerball subjects with amenorrhea reported by 71.6% and 49% of subjects,
      respectively. The mean procedure times were 3.1 minutes for Minerva and 17.2
      minutes for rollerball. There were no intraoperative adverse events and/or
      complications reported. CONCLUSION: The results of this multicenter randomized
      controlled trial demonstrate that at the 12-month follow-up, the Minerva
      procedure produces statistically significantly higher rates of success,
      amenorrhea, and patient satisfaction as well as a shorter procedure time when
      compared with the historic criterion standard of rollerball ablation. Safety
      results were excellent and similar for both procedures.

PMID- 27687853
TI  - Conservative Management of Cesarean Scar Pregnancy Following Diagnosis via
      Magnetic Resonance Imaging.

PMID- 27687854
TI  - Integrating informal providers into a people-centered health systems approach:
      qualitative evidence from local health systems in rural Nigeria.
AB  - BACKGROUND: The presence of a large informal healthcare sector in many low- and
      middle-income countries poses both challenges and opportunities for achieving a
      people-centered health system. However, few studies have considered how informal
      providers may fit into a people-centered health systems approach. We examine the
      self-described roles and motivations of informal medicine vendors and public
      healthcare workers in rural Nigeria, as well as interactions between them, with
      the aim of identifying how local health systems may be reoriented for improved
      service delivery through a people-centered approach. METHODS: We analyzed data
      from in-depth interviews with 70 medicine vendors and 21 staff of public health
      facilities in 30 villages across Kogi, Kwara and Enugu states in Nigeria.
      Interview guides covered the respondent's or her facility's role in providing
      health services to the local community, motivation to work in her respective
      profession, and relationships and interactions with other frontline healthcare
      providers. Data were analyzed in Atlas.ti using an open coding approach. RESULTS:
      Both medicine vendors and staff of public health facilities viewed themselves as
      fulfilling an essential primary healthcare function in their villages, and
      described their main motivation as the desire to help their communities. Medicine
      vendors were acknowledged by both groups to play an important role in providing
      care close to underserved rural communities, but within a limited scope of
      practice. Vendors described referring cases beyond their self-defined capacity to
      the local public facility. Health facility staff also sent clients to vendors to
      purchase drugs that were out of stock. However, referrals were informal and
      unspecific in nature, and the degree to which relationships between vendors and
      health facility staff were collaborative was highly context-dependent despite
      their recognized interdependencies in health services provision. CONCLUSIONS:
      Policies aimed at fostering people-centered health systems should consider the
      role of informal providers in the delivery of integrated care. In the context of
      our rural study sites in Nigeria, supporting stronger and more consistent
      linkages between medicine vendors and public health facilities is a key step
      towards improving health service delivery.

PMID- 27687856
TI  - The Effect of Cushion Properties on Skin Temperature and Humidity at the Body
      Support Interface.
AB  - PURPOSE: To explore the effects of various cushions on skin temperature and
      moisture at the body-seat interface during a 2-h period of continuous sitting.
      METHOD: Seventy-eight participants were randomly assigned to sit on one of the
      three types of wheelchair cushion for unrelieved sitting over 2 h. Skin
      temperature and relative humidity (RH) were measured under the subjects' ischial
      tuberosities and thighs bilaterally with digital temperature and humidity
      sensors. Data were collected before sitting and at 15-min intervals thereafter.
      RESULTS: Participants sitting on foam-fluid hybrid cushions showed significantly
      lower skin temperatures than those sitting on air-filled and foam cushions (p <
      0.05), but RH did not differ significantly among the cushions (p = 0.97). The
      three cushions produced a similar increasing trend in RH over time and RH reached
      a plateau during the 2-h sitting period. CONCLUSION: In order to select the
      appropriate wheelchair cushion, the microclimate (heat and moisture control)
      between the body-seat interface should be considered as well as pressure
      distribution. In comparison with foam-fluid hybrid cushions, the air-filled
      rubber and foam cushions tended to increase skin temperature by several degrees
      after prolonged sitting. However, cushion materials did not have significant
      differences in moisture accumulations.

PMID- 27687855
TI  - Adolescent Female Text Messaging Preferences to Prevent Pregnancy After an
      Emergency Department Visit: A Qualitative Analysis.
AB  - BACKGROUND: Over 15 million adolescents use the emergency department (ED) each
      year in the United States. Adolescent females who use the ED for medical care
      have been found to be at high risk for unintended pregnancy. Given that
      adolescents represent the largest users of text messaging and are receptive to
      receiving text messages related to their sexual health, the ED visit represents
      an opportunity for intervention. OBJECTIVE: The aim of this qualitative study was
      to explore interest in and preferences for the content, frequency, and timing of
      an ED-based text message intervention to prevent pregnancy for adolescent
      females. METHODS: We conducted semistructured, open-ended interviews in one urban
      ED in the United States with adolescent females aged 14-19 years. Eligible
      subjects were adolescents who were sexually active in the past 3 months,
      presented to the ED for a reproductive health complaint, owned a mobile phone,
      and did not use effective contraception. Using an interview guide, enrollment
      continued until saturation of key themes. The investigators designed sample text
      messages using the Health Beliefs Model and participants viewed these on a mobile
      phone. The team recorded, transcribed, and coded interviews based on thematic
      analysis using the qualitative analysis software NVivo and Excel. RESULTS:
      Participants (n=14) were predominantly Hispanic (13/14; 93%), insured (13/14;
      93%), ED users in the past year (12/14; 86%), and frequent text users (10/14; 71%
      had sent or received >30 texts per day). All were interested in receiving text
      messages from the ED about pregnancy prevention, favoring messages that were
      "brief," "professional," and "nonaccusatory." Respondents favored texts with
      links to websites, repeated information regarding places to receive
      "confidential" care, and focused information on contraception options and
      misconceptions. Preferences for text message frequency varied from daily to
      monthly, with random hours of delivery to maintain "surprise." No participant
      feared that text messages would violate her privacy. CONCLUSIONS: Adolescent
      female patients at high pregnancy risk are interested in ED-based pregnancy
      prevention provided by texting. Understanding preferences for the content,
      frequency, and timing of messages can guide in designing future interventions in
      the ED.

PMID- 27687857
TI  - Triterpenoids from Abies faxoniana and their cytotoxic activities.
AB  - Two previously unreported triterpenoids (1 and 2) and four known compounds were
      isolated from Abies faxoniana. Compound 1 has a alpha,beta-unsaturated-gamma
      lactone ring conjugated with the C-22/23 olefin in the C-17 side chain. The
      structures of the new compounds were established on the basis of spectroscopic
      data analysis. These compounds were tested for their cytotoxicities against six
      human tumour cell lines. Compound 1 showed cytotoxic activities against MCF-7 and
      A549 cells with IC50 values of 7.5 and 8.7 MUM, respectively.

PMID- 27687859
TI  - A review of emerging IL-17 inhibitors in the treatment of psoriasis focusing on
      preclinical through phase II studies.
AB  - INTRODUCTION: Interleukin-17 has recently been identified as a key player in the
      pathogenesis of psoriasis. As such, several drugs targeting IL-17 are in various
      stages of clinical development. Areas covered: In this review, the authors
      describe several emerging therapies and drug candidates targeting IL-17. The
      authors detail many biologic injectable drug candidates as well as numerous
      potential oral and topical small molecule drug candidates. Expert opinion:
      Approval of IL-17 inhibitors has significantly improved the treatment options for
      psoriasis patients. Secukinumab and ixekizumab are approved in both Europe and
      the USA, and brodalumab is likely facing approval by the end of 2016. Numerous
      additional biologic and small molecule drug candidates are in the pipeline, and
      once deemed safe and effective will likely offer significant benefit to our
      psoriasis population.

PMID- 27687858
TI  - The lung mycobiome in the next-generation sequencing era.
AB  - The fungi that reside in the human lungs represent an understudied, but medically
      relevant comm-unity. From the few studies published on the lung mycobiome, we
      find that there are fungi in both the healthy and diseased respiratory tract,
      that these fungi vary widely between individuals, and that there is a trend
      toward lower fungal diversity among individuals with disease. This review
      discusses the few studies of the lung mycobiome and details the challenges that
      accompany lung mycobiome studies. These challenges include sample collection and
      processing, sequence amplification and processing, and a history of multiple
      names for species. Some challenges may never be solved, but others can be solved
      with more data and additional studies of the lung mycobiome.

PMID- 27687861
TI  - Erratum: Sensitivity of density-dependent threshold to species composition in
      arthropod aggregates.

PMID- 27687860
TI  - The role of Silodosin as a new medical expulsive therapy for ureteral stones: a
      meta-analysis.
AB  - To evaluate the efficacy of Silodosin as a medical expulsive therapy of ureteral
      stones, we searched PubMed, EMBASE, the Cochrane Library, and CBM up to June
      2015. All randomized controlled trials (RCTs) were identified in which patients
      were randomized to receive Silodosin versus placebo or other therapies for
      ureteral stones. Outcome measures assessed were overall stone expulsion rate
      (primary) and expulsion time, analgesics times, and the incidence of additional
      treatment and regarding treatment complications (secondary). Two authors
      independently assessed study quality and extracted data. All data were analyzed
      using RevMan 5.3. Seven RCTs with a total of 1035 patients met the inclusion
      criteria. The pooled meta-analysis showed a significant improvement in stone
      clearance with Silodosin (Silodosin versus placebo, OR =1.69, 95% CI [1.19-2.40],
      p = 0.003; Silodosin versus tamsulosin, OR =2.82, 95% CI [1.79-4.44], p <
      0.00001). According to the size and location of ureteral stone, the pooling
      effects of Silodosin were analyzed, with a meaningful expulsion rate in distal
      ureteral stone when the size was 5-10 mm. In addition, a shorter expulsion time,
      fewer analgesics times, and additional treatments were observed. The common side
      effect was retrograde ejaculation. In summary, Silodosin appears to be more
      effective than either placebo or tamsulosin. Within the limits of available data,
      high-quality multicenter RCTs are needed to thoroughly evaluate the outcome in
      the future.

PMID- 27687862
TI  - Type-specific detection of herpes simplex virus type 1 and type 2 using the
      cobas(r) HSV 1 and 2 test on the cobas(r) 4800 platform.
AB  - INTRODUCTION: HSV-1 and HSV-2 are among the most common causes of sexually
      transmitted infections (stis) globally. these infections are strongly associated
      with increased risk of hiv acquisition and rare, but devastating, neonatal
      disease. available treatment options can reduce HSV transmission and improve
      quality of life. accurate diagnosis early in disease can improve patient
      management. Areas covered: This paper describes the clinical manifestations of
      HSV infection often used for clinical diagnostic purposes. The paper then
      describes the evolution of laboratory diagnostic assays. Serology, culture and
      molecular diagnostics are described since all are currently in use. The features
      and performance characteristics of the cobas 4800 HSV1 and HSV2 Test (cobas HSV)
      on the cobas 4800(r) system (cobas 4800) are described in detail. Expert
      commentary: Diagnosis of HSV has historically been unreliable or technically
      difficult, but the availability of molecular assays such as the cobas HSV test
      for detection and typing of herpes can improve our ability to correctly manage
      this disease. Utilization of tools such as the cobas HSV assay may help shorten
      the time to accurate diagnosis and treatment thus potentially reducing the risk
      of transmission and the global burden of HSV.

PMID- 27687863
TI  - Simple and rapid direct cloning and heterologous expression of natural product
      biosynthetic gene cluster in Bacillus subtilis via Red/ET recombineering.
AB  - Heterologous expression of biosynthetic pathways is an important way to research
      and discover microbial natural products. Bacillus subtilis is a suitable host for
      the heterologous production of natural products from bacilli and related
      Firmicutes. Existing technologies for heterologous expression of large
      biosynthetic gene clusters in B. subtilis are complicated. Herein, we present a
      simple and rapid strategy for direct cloning based heterologous expression of
      biosynthetic pathways in B. subtilis via Red/ET recombineering, using a 5.2 kb
      specific direct cloning vector carrying homologous sequences to the amyE gene in
      B. subtilis and CcdB counterselection marker. Using a two-step procedure, two
      large biosynthetic pathways for edeine (48.3 kb) and bacillomycin (37.2 kb) from
      Brevibacillus brevis X23 and B. amyloliquefaciens FZB42, respectively, were
      directly cloned and subsequently integrated into the chromosome of B. subtilis
      within one week. The gene cluster for bacillomycin was successfully expressed in
      the heterologous host, although edeine production was not detectable. Compared
      with similar technologies, this method offers a simpler and more feasible system
      for the discovery of natural products from bacilli and related genera.

PMID- 27687864
TI  - The domesticated brain: genetics of brain mass and brain structure in an avian
      species.
AB  - As brain size usually increases with body size it has been assumed that the two
      are tightly constrained and evolutionary studies have therefore often been based
      on relative brain size (i.e. brain size proportional to body size) rather than
      absolute brain size. The process of domestication offers an excellent opportunity
      to disentangle the linkage between body and brain mass due to the extreme
      selection for increased body mass that has occurred. By breeding an intercross
      between domestic chicken and their wild progenitor, we address this relationship
      by simultaneously mapping the genes that control inter-population variation in
      brain mass and body mass. Loci controlling variation in brain mass and body mass
      have separate genetic architectures and are therefore not directly constrained.
      Genetic mapping of brain regions indicates that domestication has led to a larger
      body mass and to a lesser extent a larger absolute brain mass in chickens, mainly
      due to enlargement of the cerebellum. Domestication has traditionally been linked
      to brain mass regression, based on measurements of relative brain mass, which
      confounds the large body mass augmentation due to domestication. Our results
      refute this concept in the chicken.

PMID- 27687865
TI  - Arsenic prepared by Chinese alchemist-pharmacists.

PMID- 27687867
TI  - Nonlinear optical observation of coherent acoustic Dirac plasmons in thin-film
      topological insulators.
AB  - Low-energy collective electronic excitations exhibiting sound-like linear
      dispersion have been intensively studied both experimentally and theoretically
      for a long time. However, coherent acoustic plasmon modes appearing in time
      domain measurements are rarely observed due to Landau damping by the single
      particle continua. Here we report on the observation of coherent acoustic Dirac
      plasmon (CADP) modes excited in indirectly (electrostatically) opposite-surface
      coupled films of the topological insulator Bi2Se3. Using transient second
      harmonic generation, a technique capable of independently monitoring the in-plane
      and out-of-plane electron dynamics in the films, the GHz-range oscillations were
      observed without corresponding oscillations in the transient reflectivity. These
      oscillations were assigned to the transverse magnetic and transverse electric
      guided CADP modes induced by the evanescent guided Lamb acoustic waves and
      remained Landau undamped due to fermion tunnelling between the opposite-surface
      Dirac states.

PMID- 27687866
TI  - Genetic controls of DNA damage avoidance in response to acetaldehyde in fission
      yeast.
AB  - Acetaldehyde, a primary metabolite of alcohol, forms DNA adducts and disrupts the
      DNA replication process, causing genomic instability, a hallmark of cancer.
      Indeed, chronic alcohol consumption accounts for approximately 3.6% of all
      cancers worldwide. However, how the adducts are prevented and repaired after
      acetaldehyde exposure is not well understood. In this report, we used the fission
      yeast Schizosaccharomyces pombe as a model organism to comprehensively understand
      the genetic controls of DNA damage avoidance in response to acetaldehyde. We
      demonstrate that Atd1 functions as a major acetaldehyde detoxification enzyme
      that prevents accumulation of Rad52-DNA repair foci, while Atd2 and Atd3 have
      minor roles in acetaldehyde detoxification. We found that acetaldehyde causes DNA
      damage at the replication fork and activates the cell cycle checkpoint to
      coordinate cell cycle arrest with DNA repair. Our investigation suggests that
      acetaldehyde-mediated DNA adducts include interstrand-crosslinks and DNA-protein
      crosslinks. We also demonstrate that acetaldehyde activates multiple DNA repair
      pathways. Nucleotide excision repair and homologous recombination, which are both
      epistatically linked to the Fanconi anemia pathway, have major roles in
      acetaldehyde tolerance, while base excision repair and translesion synthesis also
      contribute to the prevention of acetaldehyde-dependent genomic instability. We
      also show the involvement of Wss1-related metalloproteases, Wss1 and Wss2, in
      acetaldehyde tolerance. These results indicate that acetaldehyde causes cellular
      stresses that require cells to coordinate multiple cellular processes in order to
      prevent genomic instability. Considering that acetaldehyde is a human carcinogen,
      our genetic studies serve as a guiding investigation into the mechanisms of
      acetaldehyde-dependent genomic instability and carcinogenesis.

PMID- 27687868
TI  - SMC4, which is essentially involved in lung development, is associated with lung
      adenocarcinoma progression.
AB  - Structural maintenance of chromosome 4 (SMC4) is a core subunit of condensin
      complexes that mainly contributes to chromosome condensation and segregation. Our
      previous study demonstrated that the gene expression profile during lung
      development is of great values for the study of lung cancer. In this study, we
      identified SMC4 through co-expression network analysis and clique percolation
      clustering using genes that constant changes during four stages of lung
      development. Gene ontology and KEGG pathway enrichment analysis demonstrated that
      SMC4 is closely related to cell cycle, cell adhesion, and RNA processing in lung
      development and carcinogenesis. Moreover, SMC4 is overexpressed in lung
      adenocarcinoma tissues and acts as an independent prognostic factor. SMC4
      knockdown significantly inhibits the proliferation and invasion of A549 cells.
      Furthermore, we found that SMC4 interacts with DDX46 (DEAD-box helicase 46). In
      conclusion, the pivotal role of SMC4 in lung development and carcinogenesis
      suggests that genes with a similar expression pattern to SMC4 in lung development
      may also contribute to lung cancer progression. The identification of genes that
      are essentially involved in development through a comparative study between
      development and cancer may be a practical strategy for discovering potential
      biomarkers and illuminating the mechanisms of carcinogenesis.

PMID- 27687869
TI  - Allogeneic hematopoietic stem cell transplant in adult patients with
      myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes.
AB  - MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes
      are myeloid malignancies for which allogeneic hematopoietic stem cell transplant
      (allo-HSCT) is potentially curative. We describe transplant outcomes of 43
      patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast
      transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median
      follow-up of 21 months, overall survival (OS), cumulative incidence of relapse
      (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML
      without BT and 47%, 40%, and 34% respectively in CMML with BT. Higher HSCT
      comorbidity index (HSCT-CI >3 versus <=3; p = 0.015) and splenomegaly (p = 0.006)
      predicted worse OS in CMML without BT. In CMML with BT, engraftment failure (p =
      0.006) and higher HSCT-CI (p = 0.03) were associated with inferior OS, while HSCT
      within 1-year of diagnosis was associated with improved OS (p = 0.045). In
      MDS/MPN,U, at median follow-up of 15 months, OS, CIR, and NRM were 62%, 30%, and
      14%, respectively.

PMID- 27687870
TI  - Neuro-visual rehabilitation.
AB  - Despite the fact that almost one-third of patients suffer from visual deficits
      following brain damage; neuro-visual rehabilitation to compensate for visual
      field deficits is relatively neglected in the clinical setting. This is in
      contrast to physio and speech therapies, which are the bread and butter of
      rehabilitative programs. Likewise, programs that address coping with dementia
      usually concentrate on language, memory and cognitive skills, but often fail to
      address the deficits experienced by the subset of patients suffering from
      progressive cortico-visual dysfunction. Herein, we will review the different
      approaches to neuro-visual rehabilitation, mainly concentrating on restorative
      and compensatory treatments. While the first claims to restore vision in the
      blind visual field, the latter attempts to improve the use of the remaining
      intact field. These approaches differ in their premise regarding the ability of
      the adult human brain to adapt following damage, reflecting different attitudes
      toward the presumed treatment target organ. While restorative therapies claim to
      reactivate inactive neurons within or around the damaged cortices, compensatory
      approaches aim to improve voluntary eye movements to compensate the visual loss.
      We will also briefly discuss the use of optical devices for bypassing the visual
      deficit as well as the use of the blind-sight phenomena to convert non-conscious
      visual abilities in the blind visual field into awareness. The various
      therapeutic approaches will be discussed in the context of patients suffering
      from hemianopsia and in patients suffering from posterior cortical atrophy. We
      will argue that of all, the compensatory strategies have shown the most promising
      results.

PMID- 27687871
TI  - Extremely Acidic Soils are Dominated by Species-Poor and Highly Specific Fungal
      Communities.
AB  - Highly acidic soils (pH < 3) represent an environment which might potentially
      offer new biotechnologically interesting fungi. Nevertheless, only little data on
      fungal communities in highly acidic habitats are available. Here, we focused on
      the diversity of cultivable filamentous microfungi in highly acidic soils (pH <
      3) in the Czech Republic. Altogether, 16 soil samples were collected from four
      sampling sites and were processed by various approaches. In total, 54 fungal taxa
      were isolated and identified using classical as well as molecular markers. All
      dominant species were found both as living mycelia and as resistant stages.
      Numerous recently described or unknown taxa were isolated. The core of the fungal
      assemblage under study consisted of phylogenetically unrelated and often globally
      distributed fungi exclusively inhabiting highly acidic habitats like Acidiella
      bohemica, Acidomyces acidophilus, and unidentified helotialean fungus, as well as
      taxa known from less acidic and often extreme environments like Acidea extrema,
      Penicillium simplicissimum s.l., and Penicillium spinulosum. The large number of
      identified specialized species indicates that highly acidic environments provide
      suitable conditions for the evolution of specialist species. The occurrence of
      ubiquitous fungi in highly acidic substrates points to the principal role of
      competition in the colonization of such environments. The detected taxa did not
      require low pH to survive, because they can grow in a broad range of pH.

PMID- 27687872
TI  - A Metabarcoding Survey on the Fungal Microbiota Associated to the Olive Fruit
      Fly.
AB  - The occurrence of interaction between insects and fungi is interesting from an
      ecological point of view, particularly when these interactions involve insect
      pests and plant pathogens within an agroecosystem. In this study, we aimed to
      perform an accurate analysis on the fungal microbiota associated to Bactrocera
      oleae (Rossi) through a metabarcoding approach based on 454 pyrosequencing. From
      this analysis, we retrieved 43,549 reads that clustered into 128 operational
      taxonomic units (OTUs), of which 29 resulted in the "core" associate fungi of B.
      oleae. This fungal community was mainly represented by sooty mould fungi, such as
      Cladosporium spp., Alternaria spp. and Aureobasidium spp., by plant pathogens
      like Colletotrichum spp. and Pseudocercospora spp., along with several other less
      abundant taxa whose ecology is unclear in most of the cases. Our findings lead to
      new insights into the microbial ecology of this specific ecological niche,
      enabling the understanding of a complex network of interactions within the olive
      agroecosystem.

PMID- 27687873
TI  - Mitochondria isolated from the striatum brain of acute paraquat treated rats
      exhibit a higher degree of oxidative phosphorylation coupling, which shows that
      they are not subject to energetic dysfunction upon acute paraquat administration.

PMID- 27687874
TI  - Response to the Letter to the Editor: "Mitochondria isolated from the striatum of
      the brain exhibit a higher degree of oxidative phosphorylation coupling, which
      shows that they are not subject to energetic dysfunction upon acute paraquat
      administration".

PMID- 27687875
TI  - Intention and Moral Enhancement.
AB  - Recently philosophers have proposed a wide variety of interventions referred to
      as 'moral enhancements'. Some of these interventions are concerned with helping
      individuals make more informed decisions; others, however, are designed to compel
      people to act as the intervener sees fit. Somewhere between these two extremes
      lie interventions designed to direct an agent's attention either towards morally
      relevant issues - hat-hanging - or away from temptations to do wrong - hat
      hiding. I argue that these interventions fail to constitute genuine moral
      enhancement because, although they may result in more desirable outcomes - more
      altruism, more law-following, and/or less self-destructive behavior, they ignore
      a person's intentions, and often what makes an action right or wrong is the
      intent behind it.

PMID- 27687876
TI  - Insight into the Tribological Behavior of Liposomes in Artificial Joints.
AB  - Liposomes are widely used in drug delivery and gene therapy, and their new role
      as boundary lubricant in natural/artificial joints has been found in recent
      years. In this study, the tribological properties of liposomes on titanium alloy
      (Ti6Al4 V)/UHMWPE interface were studied by a ball-on-disc tribometer. The
      efficient reduction of friction coefficient and wear on both surfaces under
      various velocities and loads is found. A multilayer structure of physically
      adsorbed liposomes on Ti6Al4 V surface was also observed by atomic force
      microscope (AFM). Except for the hydration mechanism by phosphatidylcholine (PC)
      groups, the well-performed tribological properties by liposomes is also
      attributed to the existence of adsorbed liposome layers on both surfaces, which
      could reduce asperities contact and show great bearing capacity. This work
      enriches the research on liposomes for lubrication improvement on artificial
      surface and shows their value in clinical application.

PMID- 27687877
TI  - Tuning graphitic oxide for initiator- and metal-free aerobic epoxidation of
      linear alkenes.
AB  - Graphitic oxide has potential as a carbocatalyst for a wide range of reactions.
      Interest in this material has risen enormously due to it being a precursor to
      graphene via the chemical oxidation of graphite. Despite some studies suggesting
      that the chosen method of graphite oxidation can influence the physical
      properties of the graphitic oxide, the preparation method and extent of oxidation
      remain unresolved for catalytic applications. Here we show that tuning the
      graphitic oxide surface can be achieved by varying the amount and type of
      oxidant. The resulting materials differ in level of oxidation, surface oxygen
      content and functionality. Most importantly, we show that these graphitic oxide
      materials are active as unique carbocatalysts for low-temperature aerobic
      epoxidation of linear alkenes in the absence of initiator or metal. An optimum
      level of oxidation is necessary and materials produced via conventional
      permanganate-based methods are far from optimal.

PMID- 27687878
TI  - Genetic homogenization of the nuclear ITS loci across two morphologically
      distinct gentians in their overlapping distributions in the Qinghai-Tibet
      Plateau.
AB  - Interspecific hybridization and introgression can lead to partial genetic
      homogenization at certain neutral loci between morphologically distinct species
      and may obscure the species delimitation using nuclear genes. In this study, we
      investigated this phenomenon through population genetic survey of two alpine
      plants (Gentiana siphonantha and G. straminea) in the Qinghai-Tibet Plateau,
      where the distributions of two species are partly overlapped. We identified two
      clusters of chloroplast DNA haplotypes which correspond to the two species, and
      three clusters of ITS ribotypes. In addition to clusters specific to each
      species, the third ITS cluster, which was most likely derived from hybridization
      between the other two clusters and subsequent recombination and concerted
      evolution, was widely shared by two species in their adjacent areas. In contrast
      to the morphological distinctiveness of the two species, interspecific gene flow
      possibly led to genetic homogenization at their ITS loci. The new ITS lineage
      recovered for species in adjacent areas is distinctly different from original
      lineages found in allopatric areas. These findings may have general implications
      for our understanding of cryptic changes at some genetic loci caused by
      interspecific gene flow in the history, and they indicate that species
      delimitation should be based on a combination of both nuclear and chloroplast DNA
      sequence variations.

PMID- 27687879
TI  - Treatment with Hizentra in patients with primary and secondary
      immunodeficiencies: a real-life, non-interventional trial.
AB  - BACKGROUND: Although Hizentra is indicated for immunoglobulin replacement therapy
      in patients with primary and secondary immunodeficiencies, phase III trials have
      focused on patients with primary immunodeficiencies. In this 9-month, real-life,
      prospective, non-interventional, longitudinal, multicenter study of patients with
      primary and secondary immunodeficiencies in France, treatment modalities (primary
      endpoint), efficacy, safety, tolerability, quality of life, and treatment
      satisfaction were evaluated using descriptive statistics. RESULTS: Starting in
      January 2012, 117 patients were enrolled (99 adults, 18 children). Secondary
      immunodeficiencies were present in 48.7 % of patients. At follow-up, injections
      were administered every 7 days in 92.2 % of patients. Nine patients (7.8 %) were
      taking Hizentra every 10-14 days. The median dose of Hizentra administered was
      0.1 g/kg/injection. Fifty-six patients were administered doses <0.1
      g/kg/injection and 13 patients were administered doses >0.2 g/kg/injection. Mean
      trough IgG titers were 9.0 +/- 3.3 g/L (median 8.3 g/L). The mean yearly rate of
      infection was 1.2 +/- 1.9. Mean scores on the Short Form-36 physical and mental
      component summaries were 46.3 +/- 10.0 and 46.6 +/- 9.3, respectively. Scores on
      the Treatment Satisfaction Questionnaire for Medication ranged from 69.9 +/- 19.9
      to 88.3 +/- 21.2 depending on the domain. Treatment with Hizentra was well
      tolerated. No single drug-related systemic reaction occurred in more than one
      patient and few local reactions were reported (n = 5). CONCLUSIONS: Under real
      life conditions and in a cohort that included patients with primary and secondary
      immunodeficiencies, treatment with Hizentra was effective and well tolerated and
      patients were generally satisfied with the treatment.

PMID- 27687880
TI  - The influence of migraine and female hormones on capsaicin-induced dermal blood
      flow.
AB  - Background Migraine is much more common in females than in males, and occurrence
      is associated with changes in female sex hormones. Calcitonin gene-related
      peptide (CGRP) plays a key role in migraine, and variations in female sex
      hormones may affect CGRP sensitivity and/or production. Objectives Investigate
      repeatability, gender differences, influence of the menstrual cycle and of
      migraine on CGRP-dependent changes in dermal blood flow (DBF). Methods CGRP
      dependent increases in DBF were assessed using laser Doppler perfusion imaging
      after topical application of 300 or 1000 ug capsaicin on the forearm of healthy
      subjects and migraine patients. Results In healthy males, DBF response did not
      vary over time and was comparable with DBF in male migraineurs. In healthy
      females, capsaicin-induced DBF responses to both doses of capsaicin were higher
      during menstruation compared to the late-secretory phase (p < 0.05); this
      menstrual cycle dependence was absent in female migraine patients. Compared to
      healthy subjects, female migraineurs displayed a higher DBF response both during
      menstruation and during the late-secretory phase (p < 0.05). Conclusions An
      increased capsaicin-induced, CGRP-mediated DBF response was observed during
      menstruation in healthy women, but in female migraine patients this increased
      response was not affected by the menstrual cycle.

PMID- 27687881
TI  - Screening of lipase inhibitors in Folium Mori with lipase-linked magnetic
      microspheres by high-performance liquid chromatography and evaluation in diabetic
      mice.
AB  - A new method for the screening of compounds with hypoglycemic effect from
      traditional Chinese medicines employing high-performance liquid chromatography
      and lipase-linked magnetic microspheres has been proposed. We hypothesized that
      the interaction of traditional Chinese medicine extracts with lipase-linked
      magnetic microspheres should decrease the concentration of compounds with
      hypoglycemic effect. Using this approach, the potential lipase inhibitors in
      Folium Mori extract were investigated. First, lipase was immobilized on magnetic
      microspheres by a chemical method. Then, by comparing the chromatograms of
      samples before and after the interaction with lipase-linked magnetic
      microspheres, seven compounds of Folium Mori extract were identified. It was
      found that protocatechuic acid, chlorogenic acid, protocatechualdehyde, rutin,
      isoquercitrin, astragalin, and dicaffeoylquinic acid B had evident combination
      with lipase-linked magnetic microspheres. Their hypoglycemic effects were
      verified in streptozocin-induced diabetic mice. In the present study, astragalin
      was verified to improve the glucose tolerance and lower the level of glucose in
      streptozocin-induced diabetic mice, which indicated that astragalin might be a
      new highly efficient lipase inhibitor. Based on these significant results, this
      method could be a convenient approach to screen potential lipase inhibitors from
      traditional Chinese medicines. Meanwhile, it also could be expanded to screen
      other active compounds in traditional Chinese medicines.

PMID- 27687882
TI  - Reference values for serum leptin in healthy non-obese children and adolescents.
AB  - BACKGROUND: Adipokines are biologically active, low-molecular weight peptides,
      which play a major role in metabolic homeostasis in humans. Leptin has gained
      increasing attention in pediatrics as a biomarker for various metabolic
      pathologies. Yet, its usefulness is hampered by the relative lack of reference
      values from pediatric settings. Accordingly, this study aims to evaluate serum
      concentrations of leptin, soluble leptin receptor (sOB-R), and free leptin index
      (FLI) in healthy Danish schoolchildren aged 6-18 years and subsequently to
      establish reference intervals across sex and age groups. METHODS: A total of 1193
      healthy, non-obese Danish schoolchildren (730 girls, 463 boys) aged 6-18 years
      (median 11.9) were examined by trained medical staff. Serum leptin and sOB-R
      concentrations in venous fasting blood samples were quantitated by immunoassay.
      Percentile curves of leptin, sOB-R, and free leptin index were calculated using
      the General Additive Model for Location Scale and Shape (GAMLSS). RESULTS:
      Significant age and sex-dependent differences in circulating leptin levels were
      found. In boys, the median leptin concentration for all ages combined was 3.35
      MUg/L (95%-interval: 0.71-22.47) and in girls, it was 9.89 ng/L (95%-interval:
      2.06-41.49). For SOB-R, no sex-specific difference was found, and the median sOB
      R concentration was 8.24 MUg/L (IQR: 3.58-23.74; range: < 1.56-744.15).
      CONCLUSION: We demonstrated an age-dependent correlation with both serum leptin
      concentration and free leptin index with a gradual and significant increase in
      girls throughout childhood and adolescence and a significantly higher leptin
      concentration and free leptin index bell-shaped peak in early adolescence in
      boys.

PMID- 27687883
TI  - Independent and incremental prognostic value of exercise stress echocardiography
      in low cardiovascular risk female patients with chest pain.
AB  - BACKGROUND: Exercise stress echocardiography (ESEcho) is sufficiently sensitive
      and has high enough specificity for the clinical detection of coronary artery
      disease (CAD) in women. However, there was little data about the ability of
      ESEcho to detect CAD and predict clinical outcomes in female patients with chest
      pain and low global cardiovascular (CV) risks. The purposes of this study were
      (1) to determine the diagnostic accuracy of ESEcho, (2) to evaluate the clinical
      outcomes of major cardiovascular outcome (MACE), and (3) to assess the
      incremental prognostic value of ESEcho for the prediction of MACE in Korean
      female patients with low CV risks. METHODS: Over a period of 15 years, 3396
      patients (57+/-10 years) female patients with chest pain but no previous history
      of CAD undergoing ESEcho and exercise stress electrocardiography (ESECG) were
      assessed. RESULTS: During a median follow-up period of 4.8 years (2.8-6.2 years),
      there were 19 (0.61%) MACE. Positive results for ESEcho were seen in 134 patients
      (3.9%). The sensitivity and specificity of ESEcho were 66.7% and 84.8%,
      respectively. Positive ESEcho was an independent predictor of MACE (multivariate
      hazard ratio: 0.019, 95% CI: 0.004-0.081). ESEcho was incremental to clinical and
      ESECG parameters to predict the MACE in low CV risk women. CONCLUSIONS: ESEcho is
      effective for the diagnosis of CAD in Korean female patients with chest pain, a
      population characterized by low cardiovascular risk profiles. Positive ESEcho was
      an independent predictor of MACE, and negative results were associated with
      favorable clinical outcomes. ESEcho was incremental to clinical and ESECG
      parameters to predict the MACE in low CV risk women.

PMID- 27687884
TI  - Neuromuscular and inflammatory responses to handball small-sided games: the
      effects of physical contact.
AB  - The aim of this study was to investigate the influence of physical contact on
      neuromuscular impairments and inflammatory response during handball small-sided
      games. Using a counterbalanced design, 12 elite male junior handball players were
      divided into two groups: contact (C-SSG) and no-contact (NC-SSG), performing both
      contact and no-contact small-sided games, in reverse order on two training
      sessions separated by 5 days. The methodology and rules were identical for the
      two SSG regimens, with the only difference being the inclusion or prohibition of
      upper body use for physical contacts. Upper and lower body neuromuscular
      performances and blood concentrations of inflammatory cytokine IL-6 were assessed
      before and immediately after the games. During small-sided games, video analysis
      was used to establish the physical contact counts. Significant differences were
      found in most upper and lower limbs muscles kinetic variables and in the physical
      contact events (all P < 0.001) following the two training regimens. There was an
      increase in IL-6 after C-SSG and no changes following NC-SSG (P < 0.05 and P =
      0.12, respectively). Moreover, a strong correlation was found between the number
      of physical contacts and IL-6 responses (r = 0.971, P < 0.001) in C-SSG. This
      study indicates that an inflammatory response and large upper and lower body
      neuromuscular impairments result from physical contact in elite handball players.
      These outcomes outline the specific physiological profile of C-SSG that, in turn,
      might be used by practitioners and coaches as a practical approach to
      strategically select exercises in athlete's overall training program.

PMID- 27687885
TI  - Characterizing the hypomethylated DNA methylation profile of nucleated red blood
      cells from cord blood.
AB  - AIM: To provide insight into fetal nucleated red blood cell (nRBC) development
      using genome-wide DNA methylation (DNAm) profiling. MATERIALS & METHODS: The DNAm
      profile (Illumina 450K array) of cord blood (n = 7) derived nRBCs was compared
      with B cells, CD4 and CD8 T cells, natural killer cells, granulocytes, monocytes
      and placenta (n = 5). RESULTS: nRBCs and placenta had similarly low array-wide
      DNAm compared with white blood cells, but their patterns of hypomethylation
      differed at biologically relevant subsets of the array. High interindividual
      variability in nRBC DNAm was driven by a negative association between DNAm and
      nRBC count. CONCLUSION: nRBC hypomethylation is likely an epigenetic signature of
      erythropoiesis rather than of early development. Variability in nRBC DNAm may
      stem from differences in the cell population's maturity or hematopoietic source.

PMID- 27687886
TI  - Development and Validation of a SPME-GC-MS Method for In situ Passive Sampling of
      Root Volatiles from Glasshouse-Grown Broccoli Plants Undergoing Below-Ground
      Herbivory by Larvae of Cabbage Root Fly, Delia radicum L.
AB  - INTRODUCTION: Research on plant root chemical ecology has benefited greatly from
      recent developments in analytical chemistry. Numerous reports document techniques
      for sampling root volatiles, although only a limited number describe in situ
      collection. OBJECTIVES: To demonstrate a new method for non-invasive in situ
      passive sampling using solid phase micro extraction (SPME), from the immediate
      vicinity of growing roots. METHODS: SPME fibres inserted into
      polyfluorotetrafluoroethylene (PTFE) sampling tubes located in situ which were
      either perforated, covered with stainless steel mesh or with microporous PTFE
      tubing, were used for non-invasive sub-surface sampling of root volatiles from
      glasshouse-grown broccoli. Sampling methods were compared with above surface
      headspace collection using Tenax TA. The roots were either mechanically damaged
      or infested with Delia radicum larvae. Principal component analysis (PCA) was
      used to investigate the effect of damage on the composition of volatiles released
      by broccoli roots. RESULTS: Analyses by gas chromatography-mass spectrometry (GC
      MS) with SPME and automated thermal desorption (ATD) confirmed that sulphur
      compounds, showing characteristic temporal emission patterns, were the principal
      volatiles released by roots following insect larval damage. Use of SPME with in
      situ perforated PTFE sampling tubes was the most robust method for out-of-lab
      sampling. CONCLUSION: This study describes a new method for non-invasive passive
      sampling of volatiles in situ from intact and insect damaged roots using SPME.
      The method is highly suitable for remote sampling and has potential for wide
      application in chemical ecology/root/soil research. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27687887
TI  - Development of the salt-reduction and efficacy-maintenance program in Indonesia.
AB  - We conducted a randomized, controlled trial to examine the effects of a salt
      reduction and efficacy-maintenance program on the improvement and maintenance of
      self-care and self-efficacy in reducing the salt intake of older people with high
      blood pressure. A total of 51 participants with hypertension/prehypertension in
      Indonesia were randomly assigned to a control group or one of two intervention
      groups: salt-reduction training or salt-reduction and efficacy-maintenance. The
      salt-reduction and efficacy-maintenance group received educational training and a
      maintenance meeting; the participants' knowledge, attitudes, self-care practices,
      and self-efficacy significantly improved after training and were maintained after
      the maintenance meeting. Participants in the salt-reduction training group showed
      significant effects for the same variables; however, their food salt
      concentrations rebounded after the maintenance meeting. No significant
      improvement was found in the control group. The salt-reduction and efficacy
      maintenance group participants reported positive effects of salt reduction and
      different practices based on who prepared their meals. The salt-reduction and
      efficacy-maintenance group program was effective in improving and maintaining
      knowledge, attitudes, and self-efficacy of salt-reduction practices and could be
      applied with community-dwelling older people with high blood pressure.

PMID- 27687888
TI  - Immunosuppressive effects of arsenic in broiler chicks exposed to Newcastle
      disease virus.
AB  - To assess the effects of prolonged exposure to arsenic (As, as arsenate) on host
      immune competence overall and resistance to Newcastle disease (ND) viral
      infection in particular, a study was carried out in broiler chicks. At 7 days of
      age, chicks were assigned to groups that would undergo varying vaccination,
      challenge, and/or As exposures; Group 1 was a control; Group 2 was to receive
      Newcastle disease virus (NDV) only; two groups (Groups 3, 4) were to be given As
      daily (50 mg/kg, by gavage) from Days 7-35 of the experiment. All groups
      underwent normal vaccination on Days 5, 23, and 32 against live NDV (B1 type,
      LaSota strain); two groups (Groups 2, 4) were challenged with field-isolated NDV
      at Day 24. At Days 14, 21, 28, and 35 of age, subsets of chicks in each group
      were evaluated. The results showed feed intake and weight gain were lower in As
      treated and NDV-challenged chicks. In As-treated chicks, absolute and relative
      spleen weights were significantly greater, whereas those of the thymus
      significantly lower, over the entire 35-day period. Effects on bursa weights
      (absolute, relative) were only significantly reduced through Day 21. Antibody
      titers against ND were significantly reduced (vs. control) over the whole 35 days
      in birds that received As alone, but only significantly depressed through the
      first 21 days in birds that received As + NDV; thereafter, titers were
      significantly greater (in parallel with effects in birds that received NDV
      alone). In contrast, antibody responses to T-dependent antigen (Sheep red blood
      cells [SRBC]) were significantly lower in As only- and As + NDV-treated chicks
      throughout the study period. Among birds exposed to As (alone or with NDV), in
      situ phagocytic activity was elevated and cutaneous sensitivity responses
      decreased during the period from Day 28 to Day 35. NDV alone had spurious effects
      on phagocytic activity but did cause significant reductions in cutaneous
      sensitivity responses. It was concluded that arsenic decreased immunity in
      broiler chicks, thereby making them prone to ND.

PMID- 27687889
TI  - CD99 as surface anchor for human islet endocrine cell purification.
AB  - Rat and human beta cell proteomes were quantified by liquid chromatography-mass
      spectrometry/mass spectrometry (LC-MS/MS), searching for cell surface markers. In
      human beta cells, CD99 (cluster of differentiation 99) was ranked among the
      plasma membrane proteins that combine a high molar abundance with a relative
      degree of selectivity for the endocrine cells of the islets of Langerhans.
      Therefore, the applicability of CD99 as anchor for islet endocrine cell
      purification was investigated. The CD99 gene and protein expression were studied
      using microarray, LC-MS/MS, western blotting, flow cytometry and
      immunofluorescence, and a protocol was developed for magnetic bead-mediated beta
      cell enrichment from human pancreas digests using available anti-CD99 antibodies.
      In human, but not in rat, CD99 protein and mRNA were abundantly expressed by
      islet endocrine cells but undetectable in exocrine pancreas. The extracellular
      CD99 epitopes appeared to be trypsin-resistant, enabling the binding of anti-CD99
      antibodies to an insulin+/TSQ+ cell subset and efficient coupling of magnetic
      beads for positive selection of CD99+ cells. A MACS-CD99 purification of human
      pancreas fractions with low endocrine purity consistently yielded a fourfold
      enrichment of insulin+/TSQ+ cells and formation of viable and functional
      endocrine aggregates after 24 h of culture. It is concluded that CD99 is a human
      beta cell surface marker that, by virtue of its high molar abundance and
      resistance to tryptic digestion, can be used as anchor for upscalable magnetic
      bead-mediated islet endocrine cell purification. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27687890
TI  - Immediate Post-Concussion and Cognitive Testing (ImPACT): a systematic review of
      the prevalence and assessment of invalid performance.
AB  - OBJECTIVE: Computerized neuropsychological assessment of concussion has rapidly
      expanded and Immediate Post-Concussion and Cognitive Testing (ImPACT) is among
      the most commonly used measures in this domain. ImPACT was primarily developed
      for use with athletic populations but continues to expand beyond athletics to
      settings such as the workplace and schools where motivational dispositions may
      vary. The purpose of the present study was to conduct a systematic review of
      existing research investigating the prevalence of invalid baseline results and
      the effectiveness of ImPACT's embedded invalidity indicators in detecting suspect
      effort. METHOD: Preferred Reporting Items for Systematic Reviews and Meta
      Analyses guidelines were followed in order to systematically structure a search
      across four databases and analysis of studies that presented data related to the
      prevalence of invalid performance and/or the effectiveness of ImPACT's embedded
      invalidity indicators. RESULTS: A total of 17 studies included prevalence rates
      of invalid performances or examined the effectiveness of ImPACT's invalidity
      indicators. Of the 17 studies, 12 included prevalence rates of invalid baseline
      results; and across this group of studies (after removing an outlier), the
      weighted prevalence rate of invalid baseline results was 6%. Four of the 17
      studies examined the effectiveness of ImPACT's embedded invalidity indicators.
      ImPACT's embedded invalidity indicators correctly identified suboptimal effort in
      approximately 80% of individuals instructed to perform poorly and avoid detection
      ('coached') or instructed to perform poorly ('naive'). CONCLUSIONS: These
      findings raise a number of issues pertaining to the use of ImPACT. Invalid
      performance incidence may increase with large group versus individual
      administration, use in nonclinical settings, and among those with Attention
      Deficit-Hyperactivity Disorder or learning disability. Additionally, the older
      desktop version of ImPACT appears to be associated with a higher rate of invalid
      performances than the online version. Although ImPACT's embedded invalidity
      indicators detect invalid performance at a rate of 6% on average, known group
      validity studies suggest that these measures miss invalid performance
      approximately 20% of the time when individuals purposefully underperform.

PMID- 27687892
TI  - The microsurgical training programme in Gothenburg, Sweden: early experiences.
AB  - OBJECTIVE: Microsurgical techniques are increasingly used in routine surgical
      practice as well as in biomedical research. The training opportunities at
      standardised training courses are limited, and no microsurgical training facility
      or programme existed in Scandinavia before 2013. METHODS: A microsurgery
      laboratory was set up and two different courses were started, aiming separately
      at biomedical researchers and surgeons. The course for biomedical researchers
      teaches basic microsurgical skills such as vessel isolation, cannulation, and
      arterial microvascular suture under magnification. The more advanced course for
      surgeons focuses on various techniques of microvascular and nerve anastomosis.
      Both courses use a combination of theory and practice, with emphasis on the
      practical part, the course for surgeons also includes clinically relevant
      information. RESULTS: Twelve 5-day courses using both non-living models and
      exercises on laboratory animals have been conducted and attended by 49
      researchers and 44 surgeons. The organisation and the programme of the training
      courses as well as 'The 4E concept' behind the course (educational curriculum,
      equipment, ergonomy, and evaluation) are further detailed. CONCLUSIONS: We have
      successfully established the first training laboratory and series of
      microsurgical training courses in Scandinavia at two different levels. The
      experience from the first 12 courses shows the need for this type of structured
      training, and confirms that the microsurgical education curriculums needs to be
      adapted to participants' prerequisites and expectations, and various difficulty
      levels should be considered.

PMID- 27687891
TI  - Epigenetic Variability of CD4+CD25+ Tregs Contributes to the Pathogenesis of
      Autoimmune Diseases.
AB  - Autoimmune diseases are characterized by aberrant immune responses against
      healthy cells and tissues. However, the exact mechanisms underlying the
      development of these conditions remain unknown. CD4+CD25+ regulatory T cells
      (Tregs) are a subset of mature T cells which have an important role in
      maintaining immune homeostasis and preventing autoimmune diseases. Forkhead box
      p3 (Foxp3), a member of the fork head transcription factor family, is recognized
      as a marker of CD4+CD25+ Tregs. The decreased number and/or function of CD4+CD25+
      Tregs in peripheral blood and related tissues has been demonstrated in systemic
      lupus erythematosus, systemic sclerosis, and other autoimmune diseases, which are
      at least partially regulated by epigenetic mechanisms. Epigenetics refers to the
      study of potentially heritable alterations in gene expression without underlying
      changes of the nucleotide sequence, mainly including DNA methylation, histone
      modification, and microRNAs (miRNAs). For example, DNA methylation status of CpG
      islands on the Foxp3 gene, which may be affected by normal aging and regulated by
      environmental factors, plays an important role in modulating the homeostasis of
      Foxp3 expression in Tregs. Foxp3 gene in Tregs also shows distinct acetylation
      and trimethylation levels of histone H3 and H4 when compared with effector T
      cells, leading to an open chromatin structure. MicroRNAs such as miR-155, miR
      126, and miR-10a also exert an important influence on the differentiation,
      development, and immunological functions of Tregs. Aberrant epigenetic
      modifications affecting Foxp3 and other key genes in Tregs contribute to disease
      activity and tissue inflammation in autoimmune diseases, which holds great
      potential for providing novel targets for epigenetic therapies. Advances in
      research into the epigenetic regulation of CD4+CD25+ Tregs may also lead to the
      identification of new epigenetic biomarkers for diagnosis and prognosis.

PMID- 27687895
TI  - Consequences of removing cheap, super-strength beer and cider: a qualitative
      study of a UK local alcohol availability intervention.
AB  - OBJECTIVES: Increasingly, English local authorities have encouraged the
      implementation of an intervention called 'Reducing the Strength' (RtS) whereby
      off-licences voluntarily stop selling inexpensive 'super-strength' (>=6.5%
      alcohol by volume (ABV)) beers and ciders. We conceptualised RtS as an event
      within a complex system in order to identify pathways by which the intervention
      may lead to intended and unintended consequences. DESIGN: A qualitative study
      including a focus group and semistructured interviews. SETTING: An inner-London
      local authority characterised by a high degree of residential mobility, high
      levels of social inequality and a large homeless population. Intervention piloted
      in three areas known for street drinking with a high alcohol outlet density.
      PARTICIPANTS: Alcohol service professionals, homeless hostel employees, street
      based services managers and hostel dwelling homeless alcohol consumers (n=30).
      RESULTS: Participants describe a range of potential substitution behaviours to
      circumvent alcohol availability restrictions including consuming different
      drinks, finding alternative shops, using drugs or committing crimes to purchase
      more expensive drinks. Service providers suggested the intervention delivered in
      this local authority missed opportunities to encourage engagement between the
      council, alcohol services, homeless hostels and off-licence stores. Some
      participants believed small-scale interventions such as RtS may facilitate new
      forms of engagement between public and private sector interests and contribute to
      long-term cultural changes around drinking, although they may also entrench the
      view that 'problem drinking' only occurs in certain population groups.
      CONCLUSIONS: RtS may have limited individual-level health impacts if the target
      populations remain willing and able to consume alternative means of intoxication
      as a substitute for super-strength products. However, RtS may also lead to wider
      system changes not directly related to the consumption of super-strengths and
      their assumed harms.

PMID- 27687894
TI  - Isolation of a transcription factor DREB1A gene from Phaseolus vulgaris and
      computational insights into its characterization: protein modeling, docking and
      mutagenesis.
AB  - A transcription factor DREB1A (dehydration-responsive element-binding 1A) gene
      was amplified and sequenced from the common bean (Phaseolus vulgaris). PvDREB1A
      had a 777 base pairs (bp) open reading frame encoding a protein of 225 residues.
      The protein sequence contained a conserved DNA-binding AP2 domain of about 60
      residues and a nuclear localization signal (NLS) at N-terminus site. PvDREB1A
      demonstrated high homology with other DREB1 members only in AP2 domain and NLS
      site. The phylogenetic distribution of different DREB members showed three main
      groups as DREB1-3 and PvDREB1A was a member of DREB1 group. Homology modeling and
      secondary structure analyses revealed that PvDREB1A AP2 domain was packed into
      the three-stranded antiparallel beta sheets (beta1-3) and an alpha helix (alpha1)
      almost parallel to these beta sheets. Moreover, DNA-binding AP2 domain of
      PvDREB1A and GCC-box containing double helix DNA were docked. The docking
      analysis showed that PvDREB1A AP2 domain could bind to the major groove of the
      DNA by three-stranded antiparallel beta sheets, with residues Gly86 or Thr87 in
      beta1-sheet and Arg63 or Arg64 in beta3-sheet. The docked complex also indicated
      that AP2 domain has a preferential for the binding of GCC stretches in the double
      helix DNA. A total of 36 reliably estimated hot spots residues were identified
      with high mutability grade but none of these residues was essential for the
      protein function since they are located at outside the DNA-binding AP2 domain of
      PvDREB1A.

PMID- 27687896
TI  - Delayed discharges at a major arterial centre: a 4-month cross-sectional study at
      a single specialist vascular surgery ward.
AB  - OBJECTIVES: Delayed discharges are a significant problem for the National Health
      Service. The objectives of this study were to determine the prevalence and impact
      of delayed discharge at a single specialist vascular surgery ward. DESIGN: A
      cross-sectional observational study. SETTING: A single specialist vascular unit
      in the UK during a 4-month study period (01/09/2014-31/12/2014). PARTICIPANTS:
      All patients admitted to the ward during the study period were included. Patients
      spending >=1 night on the ward once declared medically fit for discharge (MFFD)
      were prospectively identified and data prospectively collected. All other
      patients were identified retrospectively with data collected retrospectively from
      electronic records. OUTCOME MEASURES: Primary outcome was number of patients
      experiencing delayed discharge. Secondary outcome measures were length of stay,
      length of delay and cost of delay. RESULTS: There were 268 admissions with a
      total length of stay (LoS) of 2776 days. 57 admissions (21.3%) experienced
      delayed discharges with a total 535 excess bed days (19.3% total LoS) once MFFD.
      Unplanned admission (relative risk 7.3 (95% CI 2.7 to 20.0; p<0.001)) and index
      amputation (relative risk 9.2 (95% CI 3.8 to 22.0; p<0.001)) were associated with
      increased risk of delayed discharge. There were significant differences in the
      length of delay by the reason for the delay (p=0.01). Delay due to the provision
      of social services and inpatient rehabilitation were associated with longer
      length of delay (post hoc analysis). Age was not independently associated with
      either increased risk of delayed discharge or length of delay.The total estimated
      cost of delayed discharges during the study period was L146 055. CONCLUSIONS: A
      significant number of vascular patients experience delayed discharge. MFFD
      vascular patients occupy a high proportion of vascular beds at considerable
      financial cost. Unplanned admissions, amputees and those delayed due to social
      services contributed most to delays. Closer integration with community health and
      social care providers may reduce delays.

PMID- 27687893
TI  - LncRNA mediated regulation of aging pathways in Drosophila melanogaster during
      dietary restriction.
AB  - Dietary restriction (DR) extends lifespan in many species which is a well-known
      phenomenon. Long non-coding RNAs (lncRNAs) play an important role in regulation
      of cell senescence and important age-related signaling pathways. Here, we
      profiled the lncRNA and mRNA transcriptome of fruit flies at 7 day and 42 day
      during DR and fully-fed conditions, respectively. In general, 102 differentially
      expressed lncRNAs and 1406 differentially expressed coding genes were identified.
      Most informatively we found a large number of differentially expressed lncRNAs
      and their targets enriched in GO and KEGG analysis. We discovered some new aging
      related signaling pathways during DR, such as hippo signaling pathway-fly,
      phototransduction-fly and protein processing in endoplasmic reticulum etc. Novel
      lncRNAs XLOC_092363 and XLOC_166557 are found to be located in 10 kb upstream
      sequences of hairy and ems promoters, respectively. Furthermore, tissue
      specificity of some novel lncRNAs had been analyzed at 7 day of DR in fly head,
      gut and fat body. Also the silencing of lncRNA XLOC_076307 resulted in altered
      expression level of its targets including Gadd45 (involved in FoxO signaling
      pathway). Together, the results implicated many lncRNAs closely associated with
      dietary restriction, which could provide a resource for lncRNA in aging and age
      related disease field.

PMID- 27687897
TI  - Knowledge and practice of prostate cancer screening among general practitioners
      in Malaysia: a cross-sectional study.
AB  - OBJECTIVE: Screening for prostate cancer remains controversial. General
      practitioners (GPs) play an important role in assisting men to make an informed
      decision on prostate cancer screening. The aim of this study was to determine the
      knowledge and practice of prostate cancer screening among private GPs in
      Malaysia. DESIGN: A cross-sectional study. SETTING: Private general practices in
      Selangor, Malaysia. PARTICIPANTS: 311 randomly selected full-time private GPs
      were recruited between September 2013 and January 2014. OUTCOME MEASURES:
      Questionnaires were distributed to the GPs via postal mail and clinic visits. The
      main outcomes were: knowledge of prostate cancer risk factors and screening
      tests; GPs' prostate cancer screening practices; and factors influencing GPs'
      decision to screen for prostate cancer. Associations between covariates and
      propensity to screen for prostate cancer were determined using logistic
      regression. RESULTS: The response rate was 65%. The proportion of GPs who
      overestimated the positive predictive values of prostrate-specific antigen (PSA),
      digital rectal examination (DRE) and a combination of PSA and DRE was 63%, 57%
      and 64%, respectively. About 49.5% of the respondents would routinely screen
      asymptomatic men for prostate cancer; of them, 94.9% would use PSA to screen.
      Male GPs who would consider having a PSA test performed on themselves were six
      times more likely to screen asymptomatic men than GPs who would not have the test
      (OR=6.88, 95% CI 1.40 to 33.73), after adjusting for age and duration of
      practice. CONCLUSIONS: GPs overestimated the accuracy of PSA in prostate cancer
      screening. Their intention to screen for prostate cancer themselves predicted
      their propensity to screen their patients for prostate cancer. This finding
      highlights the potential of using a new approach to change GPs' screening
      practices via addressing GPs' own screening behaviour.

PMID- 27687898
TI  - Effect of modelling slum populations on influenza spread in Delhi.
AB  - OBJECTIVES: This research studies the impact of influenza epidemic in the slum
      and non-slum areas of Delhi, the National Capital Territory of India, by taking
      proper account of slum demographics and residents' activities, using a highly
      resolved social contact network of the 13.8 million residents of Delhi. METHODS:
      An SEIR model is used to simulate the spread of influenza on two different
      synthetic social contact networks of Delhi, one where slums and non-slums are
      treated the same in terms of their demographics and daily sets of activities and
      the other, where slum and non-slum regions have different attributes. RESULTS:
      Differences between the epidemic outcomes on the two networks are large. Time-to
      peak infection is overestimated by several weeks, and the cumulative infection
      rate and peak infection rate are underestimated by 10-50%, when slum attributes
      are ignored. CONCLUSIONS: Slum populations have a significant effect on influenza
      transmission in urban areas. Improper specification of slums in large urban
      regions results in underestimation of infections in the entire population and
      hence will lead to misguided interventions by policy planners.

PMID- 27687899
TI  - Central corneal thickness changes in bevel-up versus bevel-down
      phacoemulsification cataract surgery: study protocol for a randomised, triple
      blind, parallel group trial.
AB  - INTRODUCTION: Corneal endothelial damage following phacoemulsification is still
      one of the major concerns of modern day cataract surgery. Although many
      techniques have been proposed, the risks of posterior capsular rupture and
      corneal endothelium damage persist. In theory, damage to the corneal endothelium
      is minimised by delivering the lowest phaco energy only in the direction
      necessary to emulsify the lens nucleus. Hence, it is believed that the bevel of
      the needle should be turned towards the nucleus or the nuclear fragment (ie,
      bevel-down. However, there is a difference of opinion among ophthalmologists with
      reference to the phaco tip's position (bevel-up vs bevel-down) during
      phacoemulsification. This subject has not been extensively studied earlier.
      METHODS AND ANALYSIS: This is a prospective, triple-blinded (trial participant,
      outcome assessor and the data analyst), randomised controlled trial with 2
      parallel groups and with an allocation ratio of 1:1. It will be conducted in a
      tertiary care hospital, Mangaluru, India. The objective is to compare the
      postoperative central corneal thickness changes between the bevel-up and bevel
      down techniques of phacoemulsification. Patients aged >18 years with immature
      cataract undergoing phacoemulsification will be selected for the study. The
      important exclusion criteria are the history of previous significant ocular
      trauma or intraocular surgery, corneal pathology, pseudoexfoliation syndrome,
      intraocular inflammation, a preoperative fully dilated pupil <6 mm, anterior
      chamber depth <2.5 mm and nuclear sclerosis grade >4. After randomisation,
      patients will undergo phacoemulsification surgery either by a bevel-up or bevel
      down procedure. With an estimated power of 80%, the calculated sample size is 55
      patients in each group. The recruitment will start from April 2016. ETHICS AND
      DISSEMINATION: Yenepoya University Ethics Committee, India has approved the study
      protocol (YUEC/148/2016 on 18 February 2016). It complies with the Declaration of
      Helsinki, local laws and the International Council for Harmonization-good
      clinical practices. TRIAL REGISTRATION NUMBER: CTRI/2016/02/006691; Pre-results.

PMID- 27687900
TI  - Effectiveness of case management interventions for frequent users of healthcare
      services: a scoping review.
AB  - OBJECTIVE: Frequent users of healthcare services are a vulnerable population,
      often socioeconomically disadvantaged, who can present multiple chronic
      conditions as well as mental health problems. Case management (CM) is the most
      frequently performed intervention to reduce healthcare use and cost. This study
      aimed to examine the evidence of the effectiveness of CM interventions for
      frequent users of healthcare services. DESIGN: Scoping review. DATA SOURCES: An
      electronic literature search was conducted using the MEDLINE, Scopus and CINAHL
      databases covering January 2004 to December 2015. A specific search strategy was
      developed for each database using keywords 'case management' and 'frequent use'.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: To be included in the review, studies
      had to report effects of a CM intervention on healthcare use and cost or patient
      outcomes. Eligible designs included randomised and non-randomised controlled
      trials and controlled and non-controlled before-after studies. Studies limited to
      specific groups of patients or targeting a single disease were excluded. Three
      reviewers screened abstracts, screened each full-text article and extracted data,
      and discrepancies were resolved by consensus. RESULTS: The final review included
      11 articles evaluating the effectiveness of CM interventions among frequent users
      of healthcare services. Two non-randomised controlled studies and 4 before-after
      studies reported positives outcomes on healthcare use or cost. Two randomised
      controlled trials, 2 before-after studies and 1 non-randomised controlled study
      presented mitigated results. Patient outcomes such as drug and alcohol use,
      health locus of control, patient satisfaction and psychological functioning were
      evaluated in 3 studies, but no change was reported. CONCLUSIONS: Many studies
      suggest that CM could reduce emergency department visits and hospitalisations as
      well as cost. However, pragmatic randomised controlled trials of adequate power
      that recruit the most frequent users of healthcare services are still needed to
      clearly confirm its effectiveness.

PMID- 27687901
TI  - Evidence-based interventions to reduce adverse events in hospitals: a systematic
      review of systematic reviews.
AB  - OBJECTIVE: To provide an overview of effective interventions aimed at reducing
      rates of adverse events in hospitals. DESIGN: Systematic review of systematic
      reviews. DATA SOURCES: PubMed, CINAHL, PsycINFO, the Cochrane Library and EMBASE
      were searched for systematic reviews published until October 2015. STUDY
      SELECTION: English-language systematic reviews of interventions aimed at reducing
      adverse events in hospitals, including studies with an experimental design and
      reporting adverse event rates, were included. Two reviewers independently
      assessed each study's quality and extracted data on the study population, study
      design, intervention characteristics and adverse patient outcomes. RESULTS: Sixty
      systematic reviews with moderate to high quality were included. Statistically
      significant pooled effect sizes were found for 14 types of interventions,
      including: (1) multicomponent interventions to prevent delirium; (2) rapid
      response teams to reduce cardiopulmonary arrest and mortality rates; (3)
      pharmacist interventions to reduce adverse drug events; (4) exercises and
      multicomponent interventions to prevent falls; and (5) care bundle interventions,
      checklists and reminders to reduce infections. Most (82%) of the significant
      effect sizes were based on 5 or fewer primary studies with an experimental study
      design. CONCLUSIONS: The evidence for patient-safety interventions implemented in
      hospitals worldwide is weak. The findings address the need to invest in high
      quality research standards in order to identify interventions that have a real
      impact on patient safety. Interventions to prevent delirium, cardiopulmonary
      arrest and mortality, adverse drug events, infections and falls are most
      effective and should therefore be prioritised by clinicians.

PMID- 27687902
TI  - Do baby boomers use more healthcare services than other generations? Longitudinal
      trajectories of physician service use across five birth cohorts.
AB  - OBJECTIVE: In light of concerns for meeting the provision of healthcare services
      given the large numbers of ageing baby boomers, we compared the trajectories of
      primary care and specialist services use across the lifecourse of 5 birth cohorts
      and examined factors associated with birth cohort differences. DESIGN:
      Longitudinal panel. SETTING: Canadian National Population Health Survey (1994
      2011). POPULATION: Sample of 10 186 individuals aged 20-69 years in 1994-1995 and
      who were from 5 birth cohorts: Generation X (Gen X; born: 1965-1974), Younger
      Baby Boomers (born: 1955-1964), Older Baby Boomers (born: 1945-1954), World War
      II (born: 1935-1944) and pre-World War II (born: 1925-1934). MAIN OUTCOMES: Use
      of primary care and specialist services. RESULTS: Although the overall pattern
      suggested less use of physician services by each successive recent cohort, this
      blinded differences in primary and specialist care use by cohort. Multilevel
      analyses comparing cohorts showed that Gen Xers and younger boomers, particularly
      those with multimorbidity, were less likely to use primary care than earlier
      cohorts. In contrast, specialist use was higher in recent cohorts, with Gen Xers
      having the highest specialist use. These increases were explained by the
      increasing levels of multimorbidity. Education, income, having a regular source
      of care, sedentary lifestyle and obesity were significantly associated with
      physician services use, but only partially contributed to cohort differences.
      CONCLUSIONS: The findings suggest a shift from primary care to specialist care
      among recent cohorts, particularly for those with multimorbidity. This is of
      concern given policies to promote primary care services to prevent and manage
      chronic conditions. There is a need for policies to address important
      generational differences in healthcare preferences and the balance between
      primary and specialty care to ensure integration and coordination of healthcare
      delivery.

PMID- 27687903
TI  - Patient values and preferences on transcatheter or surgical aortic valve
      replacement therapy for aortic stenosis: a systematic review.
AB  - OBJECTIVE: To investigate patients' values and preferences regarding aortic valve
      replacement therapy for aortic stenosis. SETTING: Studies published after
      transcatheter aortic valve insertion (TAVI) became available (2002).
      PARTICIPANTS: Adults with aortic stenosis who are considering or have had valve
      replacement, either TAVI or via surgery (surgical aortic valve replacement,
      SAVR). OUTCOME MEASURES: We sought quantitative measurements, or qualitative
      descriptions, of values and preferences. When reported, we examined correlations
      between preferences and objective (eg, ejection fraction) or subjective (eg,
      health-related quality of life) measures of health. RESULTS: We reviewed 1348
      unique citations, of which 2 studies proved eligible. One study of patients with
      severe aortic stenosis used a standard gamble study to ascertain that the median
      hypothetical mortality risk patients were willing to tolerate to achieve full
      health was 25% (IQR 25-50%). However, there was considerable variability; for
      mortality risk levels defined by current guidelines, 130 participants (30%) were
      willing to accept low-to-intermediate risk (<=8%), 224 (51%) high risk (>8-50%)
      and 85 (19%) a risk that guidelines would consider prohibitive (>50%). Study
      authors did not, however, assess participants' understanding of the exercise,
      resulting in a potential risk of bias. A second qualitative study of 15 patients
      identified the following factors that influence patients to undergo assessment
      for TAVI: symptom burden; expectations; information support; logistical barriers;
      facilitators; obligations and responsibilities. The study was limited by serious
      risk of bias due to authors' conflict of interest (5/9 authors industry-funded).
      CONCLUSIONS: Current evidence on patient values and preferences of adults with
      aortic stenosis is very limited, and no studies have enrolled patients deciding
      between TAVI and SAVR. On the basis of the data available, there is evidence of
      variability in individual values and preferences, highlighting the importance of
      well-informed and shared decision-making with patients facing this decision.
      TRIAL REGISTRATION NUMBER: PROSPERO CRD42016041907.

PMID- 27687904
TI  - New lanostane-type triterpenoids from the fruiting body of Ganoderma hainanense.
AB  - Five new lanostane-type triterpenoids, ganoderenses A-E (1-5), two new lanostane
      nor-triterpenoids, ganoderenses F and G (6 and 7), along with 13 known analogues
      (8-20) were isolated from the fruiting body of Ganoderma hainanense. Their
      structures were determined by combined chemical and spectral methods, and the
      absolute configurations of compounds 1 and 13 were confirmed by single crystal X
      ray diffraction. All compounds were evaluated for inhibitory activity against
      thioredoxin reductase (TrxR), a potential target for cancer chemotherapy with
      redox balance and antioxidant functions, but were inactive.

PMID- 27687905
TI  - Impact of gender on safety and efficacy of Rivaroxaban in adolescents & young
      adults with venous thromboembolism.

PMID- 27687906
TI  - Early nutrition, growth and cognitive development of infants from birth to 2
      years in Malaysia: a study protocol.
AB  - BACKGROUND: The first 2 years of life is a critical period of rapid growth and
      brain development. During this period, nutrition and environmental factors play
      important roles in growth and cognitive development of a child. This report
      describes the study protocol of early nutrition, growth and cognitive development
      of infants from birth to 2 years of age. METHODS/DESIGN: This is a prospective
      cohort study of mothers and infants recruited from government health clinics in
      Seremban district in Negeri Sembilan, Malaysia. Infants are followed-up at 6, 12,
      18 and 24 months of age. Pre-natal factors that include mother's pre-pregnancy
      body mass index, gestational weight gain, blood glucose and blood pressure during
      pregnancy, infant's gestational age, birth weight and head circumference at birth
      are obtained from patient card. Post-natal factors assessed at each follow-up are
      feeding practices, dietary intake, anthropometric measurements and cognitive
      development of infants. Iron status is assessed at 6 months, while infant
      temperament and home environment are assessed at 12 months. Maternal intelligence
      is assessed at 18 months. DISCUSSION: Early life nutritional programming is of
      current interest as many longitudinal studies are actively being conducted in
      developed countries to investigate this concept. The concept however is
      relatively new in developing countries such as Malaysia. This study will provide
      useful information on early nutrition and infant development in the first two
      years of life which can be further followed up to identify factors that track
      into childhood and contribute to growth and cognitive deviations.

PMID- 27687907
TI  - Value propositions of mHealth projects.
AB  - While mHealth holds great potential for addressing global health disparities, a
      majority of the initiatives never proceed beyond the pilot stage. One fundamental
      concern is that mHealth projects are seldom designed from the customer's
      perspective to address their specific problems and/or create appreciable value. A
      customer-centric view, where direct tangible benefits of interventions are
      identified and communicated effectively, can drive customer engagement and
      advance projects toward self-sustaining business models. This article reviews the
      business models of 234 mHealth projects to identify nine distinct value
      propositions that solve specific problems for customers. Each of these value
      propositions is discussed with real-world examples, analyses of their design
      approaches and business strategies, and common enablers as well as hurdles to
      surviving past the pilot stage. Furthermore, a deeper analysis of 42 mHealth
      ventures that have achieved self-sustainability through project revenue provides
      a host of practical and poignant insights into the design of systems that can
      fulfil mHealth's promise to address healthcare challenges in the long term.

PMID- 27687908
TI  - Early life adversity alters normal sex-dependent developmental dynamics of DNA
      methylation.
AB  - Studies in rodents, nonhuman primates, and humans suggest that epigenetic
      processes mediate between early life experiences and adult phenotype. However,
      the normal evolution of epigenetic programs during child development, the effect
      of sex, and the impact of early life adversity on these trajectories are not well
      understood. This study mapped the genome-wide DNA methylation changes in CD3+ T
      lymphocytes from rhesus monkeys from postnatal day 14 through 2 years of age in
      both males and females and determined the impact of maternal deprivation on the
      DNA methylation profile. We show here that DNA methylation profiles evolve from
      birth to adolescence and are sex dependent. DNA methylation changes accompany
      imposed weaning, attenuating the difference between males and females. Maternal
      separation at birth alters the normal evolution of DNA methylation profiles and
      targets genes that are also affected by a later stage maternal separation, that
      is, weaning. Our results suggest that early life events dynamically interfere
      with the normal developmental evolution of the DNA methylation profile and that
      these changes are highly effected by sex.

PMID- 27687909
TI  - Laparoscopic treatment of gastrocolic fistula: a rare complication post-sleeve
      gastrectomy.

PMID- 27687910
TI  - Emergency reversal of gastric bypass for missed diagnosis of internal hernia and
      bowel ischemia in a pregnant woman.

PMID- 27687911
TI  - Intragastric balloon as a bridge procedure in patients with high body mass index.

PMID- 27687912
TI  - Oxysterols: From cholesterol metabolites to key mediators.
AB  - Oxysterols are cholesterol metabolites that can be produced through enzymatic or
      radical processes. They constitute a large family of lipids (i.e. the oxysterome)
      involved in a plethora of physiological processes. They can act through GPCR
      (e.g. EBI2, SMO, CXCR2), nuclear receptors (LXR, ROR, ERalpha) and through
      transporters or regulatory proteins. Their physiological effects encompass
      cholesterol, lipid and glucose homeostasis. Additionally, they were shown to be
      involved in other processes such as immune regulatory functions and brain
      homeostasis. First studied as precursors of bile acids, they quickly emerged as
      interesting lipid mediators. Their levels are greatly altered in several
      pathologies and some oxysterols (e.g. 4beta-hydroxycholesterol or 7alpha
      hydroxycholestenone) are used as biomarkers of specific pathologies. In this
      review, we discuss the complex metabolism and molecular targets (including
      binding properties) of these bioactive lipids in human and mice. We also discuss
      the genetic mouse models currently available to interrogate their effects in
      pathophysiological settings. We also summarize the levels of oxysterols reported
      in two key organs in oxysterol metabolism (liver and brain), plasma and
      cerebrospinal fluid. Finally, we consider future opportunities and directions in
      the oxysterol field in order to gain a better insight and understanding of the
      complex oxysterol system.

PMID- 27687913
TI  - IL-27 attenuates airway inflammation in a mouse asthma model via the STAT1 and
      GADD45gamma/p38 MAPK pathways.
AB  - BACKGROUND: Asthma is prone to Th2-mediated chronic airway inflammation.
      Interleukin-27 (IL-27) is a member of the IL-12 family that promotes the
      differentiation of Th1 cells and inhibits Th2 cells. We use human/mouse CD4+ T
      cells to see whether IL-27 could inhibit IL-4 production in vitro and then
      observe whether IL-27 administration could alleviate allergic airway inflammation
      in vivo by mice asthma model. METHODS: We isolated and cultured CD4+ T cells from
      healthy humans and mice to test whether IL-27 could inhibit IL-4 production under
      different conditions. In vivo study, the effect of IL-27 was examined using two
      types of intra-nasal (i.n.) administration: low-dose-multiple-times prevention or
      high-dose-limited-times treatment in murine asthma models. The expression levels
      of signal transducer and activator of transcription-1 (STAT1) and growth arrest
      and DNA damage 45-gamma (GADD45gamma)/p38 mitogen activated protein kinase (p38
      MAPK) in lung tissues were measured using qPCR and Western blotting. RESULTS: In
      vitro, although IL-27 could inhibit naive CD4+ T cell differentiate into Th2
      cells, but it could not redifferentiate already committed Th2 cells. In vivo,
      preventative administration of IL-27 attenuated allergic inflammation and airway
      hyperreactivity, whereas treatment group had no significant effect. In the asthma
      group, the phosphorylation of STAT1 was impaired, while GADD45gamma and p38 MAPK
      exhibited no obvious changes. Preventative administration of IL-27 could either
      reverse the impairment of STAT1 or strengthen the expression of GADD45gamma and
      p38 MAPK, whereas treatment group had no significant effect. CONCLUSIONS:
      Preventative administration of IL-27 improved the pathological changes in mouse
      asthma models via both the STAT1 and GADD45gamma/p38 MAPK pathways while
      therapeutic administration of IL-27 had no significant effect, which may be due
      to the presence of already differentiated Th2 cells in asthmatic airways that
      resist IL-27 inhibition.

PMID- 27687914
TI  - Comparing the Survivability of Lactobacillus Species in Various Probiotic
      Delivery Vehicles.
AB  - BACKGROUND: Probiotics are widely used in healthy and nonhealthy individuals to
      maintain a favorable gut microbiome and inhibit pathogen takeover. Currently,
      there are many varieties of probiotic delivery vehicles on the market, with no
      real research indicating which is the most effective at allowing for colon
      colonization. In this study, we sought to determine if probiotic preparation
      influences the ability of Lactobacillus species, one of the most common genera of
      probiotic bacteria, to survive gastric acidity. OBJECTIVE: To determine the
      survivability of lactobacilli in stomach-level acidity for a variety of probiotic
      delivery vehicles. MATERIALS AND METHODS: We tested the ability of 6 different
      probiotic preparations-enterically encapsulated pills, nonencapsulated pills,
      lyophilized powder, yogurt, yogurt drink, and kefir-to enhance survivability of
      lactobacilli in pH 2.0-adjusted phosphate-buffered saline over time. Colony
      forming units were enumerated by spot plating on both nonselective (brain-heart
      infusion) and selective (Rogosa SL) agar. RESULTS: Regardless of delivery
      vehicle, lactobacilli are very capable of surviving gastric acidity, allowing for
      passage into the intestines.

PMID- 27687915
TI  - Scalable principles of community-based high-value care for seriously ill
      individuals: Diamonds in the rough.
AB  - Early, integrated palliative care has been shown to improve quality of life and
      reduce utilization in both inpatient and outpatient settings. As health systems
      shift to risk-based payment structures, palliative care will play an increasing
      role in improving value of care outside of the hospital. Based on successful
      models of community-based palliative care, we identify six principles -
      interdisciplinary team-based care; 24/7 access and responsiveness; concurrent
      palliative care with disease-directed treatment; targeting services to high-risk
      patients; integrated medical and social supports; and caregiver support - that
      are widely implemented because of their impact on improving value for seriously
      ill individuals.

PMID- 27687916
TI  - MACRAeconomics: Physician incentives and behavioral economics in the Medicare
      Access and CHIP Reauthorization Act.

PMID- 27687917
TI  - Determinants of success in Shared Savings Programs: An analysis of ACO and market
      characteristics.
AB  - BACKGROUND: Medicare's Accountable Care Organization (ACO) programs introduced
      shared savings to traditional Medicare, which allow providers who reduce health
      care costs for their patients to retain a percentage of the savings they
      generate. OBJECTIVE: To examine ACO and market factors associated with superior
      financial performance in Medicare ACO programs. METHODS: We obtained financial
      performance data from the Centers for Medicare and Medicaid Services (CMS); we
      derived market-level characteristics from Medicare claims; and we collected ACO
      characteristics from the National Survey of ACOs for 215 ACOs. We examined the
      association between ACO financial performance and ACO provider composition,
      leadership structure, beneficiary characteristics, risk bearing experience,
      quality and process improvement capabilities, physician performance management,
      market competition, CMS-assigned financial benchmark, and ACO contract start
      date. We examined two outcomes from Medicare ACOs' first performance year:
      savings per Medicare beneficiary and earning shared savings payments (a
      dichotomous variable). RESULTS: When modeling the ACO ability to save and earn
      shared savings payments, we estimated positive regression coefficients for a
      greater proportion of primary care providers in the ACO, more practicing
      physicians on the governing board, physician leadership, active engagement in
      reducing hospital re-admissions, a greater proportion of disabled Medicare
      beneficiaries assigned to the ACO, financial incentives offered to physicians, a
      larger financial benchmark, and greater ACO market penetration. No characteristic
      of organizational structure was significantly associated with both outcomes of
      savings per beneficiary and likelihood of achieving shared savings. ACO prior
      experience with risk-bearing contracts was positively correlated with savings and
      significantly increased the likelihood of receiving shared savings payments.
      CONCLUSIONS: In the first year, performance is quite heterogeneous, yet
      organizational structure does not consistently predict performance. Organizations
      with large financial benchmarks at baseline have greater opportunities to achieve
      savings. Findings on prior risk bearing suggest that ACOs learn over time under
      risk-bearing contracts. IMPLICATIONS: Given the lack of predictive power for
      organizational characteristics, CMS should continue to encourage diversity in
      organizational structures for ACO participants, and provide alternative funding
      and risk bearing mechanisms to continue to allow a diverse group of organizations
      to participate. LEVEL OF EVIDENCE: III.

PMID- 27687918
TI  - Does laminar airflow make a difference to the infection rates for lower limb
      arthroplasty: a study using the National Joint Registry and local surgical site
      infection data for two hospitals with and without laminar airflow.
AB  - This study compared the National Joint Registry for England, Wales, Northern
      Ireland and the Isle of Man (NJR) data for total hip replacements (THRs) and
      total knee replacements (TKRs) from Hospital A [with laminar airflow (LAF)] and
      Hospital B (without LAF). These hospitals were originally managed by two
      different trusts that subsequently merged. Consequently, the theatres in Hospital
      A have always had LAF and those in Hospital B had only conventional ventilation
      systems. As this merger happened before the establishment of the NJR, it puts us
      in a unique position, enabling direct comparison of the revision rates for
      infected hip and knee replacements between the two hospitals that follow similar
      infection protocols. Analysis of the NJR data showed there were no statistical
      differences. Of the 2234 TKRs performed at Hospital A, 16 were revised for
      infection, whereas 19 of the 3694 TKRs at Hospital B were revised (p < 0.33). Of
      the 1752 THRs at Hospital A, 5 were revised for infection, whereas this was the
      case for 12 of the 3163 THRs at Hospital B (p < 0.59). There was also no
      statistical difference when combining the figures for TKRs and THRs (p < 0.59).
      Our local surgical site infection (SSI) data from these two hospitals were also
      analysed. Again, there was no statistical difference between the two sites (p <
      0.34). Using LAF has not reduced the rate of revision for infection nor it has
      reduced the incidence of SSI in our theatres. This is the first study comparing
      infection rates in two different hospitals serving similar patient populations
      using the NJR and SSI data. Our study questions the rationale of increasing use
      of LAF in routine lower limb arthroplasty. We call for greater debate and more
      robust studies on the subject.

PMID- 27687919
TI  - Bone density of elbow joints in Labrador retrievers and Golden retrievers:
      Comparison of healthy joints and joints with medial coronoid disease.
AB  - The aims of this study were: (1) to determine the inter-observer repeatability of
      particular regions of the canine elbow joints; (2) to assess the effect of age,
      bodyweight and breed on bone density in healthy young dogs; (3) to compare
      Hounsfield units (HU) and bone density (BD) measurements between normal elbow
      joints and diseased elbow joints; and (4) to determine the sensitivity and
      specificity for HU and BD measurements in specific regions in the canine elbow
      joint. Regions with the highest repeatability were located at the medial coronoid
      process (MCP) base and apex, and at the level of the humerus, on the sagittal and
      sagittal oblique planes of the elbow joint. Age and breed were significantly
      associated with several regions of interest; conversely, none of the measurements
      were associated with bodyweight. Increased HU and BD values in the MCP base and
      apex regions are likely to be related to medial coronoid disease. Labrador
      retrievers had higher HU and BD values than Golden retrievers and an increase in
      BD was found in older animals. Cut-offs determined with receiver operating
      characteristic plots of the MCP base and apex suggested fairly good sensitivity
      and specificity (base: area under the curve 0.85, sensitivity 75.0%, specificity
      88.8%; apex: area under the curve 0.89, sensitivity 80.0%, specificity 92.5%). 

PMID- 27687920
TI  - Responses to diagnostic tests for bovine tuberculosis in dairy and non-dairy
      cattle naturally exposed to Mycobacterium bovis in Great Britain.
AB  - Field surveillance of British cattle using the single intradermal comparative
      cervical tuberculin (SICCT) test shows a higher incidence rate of bovine
      tuberculosis (bTB) in dairy compared to beef herds, but a lower probability of
      post-mortem examination confirmed (PMC) Mycobacterium bovis infection in dairy
      herds. A cross-sectional study was conducted to compare animal level differences
      in bTB detection between dairy and non-dairy cattle in Great Britain. During the
      period from 2002 to 2005, 200 (41% dairy) reactors in the SICCT test (standard
      interpretation) were randomly selected, and 200 in-contact cattle (43% dairy)
      were purposively selected from bTB-infected herds. Interferon (IFN)-gamma
      responses in blood to bovine and avian purified protein derivative (PPD), and
      early secretory antigen target 6 kDa and culture filtrate protein 10 (ESAT
      6/CFP10), were measured. The post-mortem examination included gross pathological
      examination, mycobacterial culture and histopathology. The proportions of cattle
      positive to ESAT6/CFP10 were 26% (95% confidence interval, CI, 15-39%) in dairy
      reactors and 62% (95% CI 51-72%) in non-dairy reactors (P <0.001). PMC risk was
      34% (95% CI 24-45%) in dairy reactors and 69% (95% CI 60-78%) in non-dairy
      reactors (P <0.001). The odds ratio for PMC risk in dairy reactors compared to
      non-dairy reactors, after controlling for bTB prevalence, herd size and SICCT
      test response, was 0.27 (95% CI 0.14-0.53; P <0.001). In surveillance data,
      adjusted animal level PMC risks were lower for dairy reactors than for beef
      reactors aged >2 years (P <0.001). 

PMID- 27687921
TI  - Effects of preoperative carprofen on cardio-respiratory, hormonal and metabolic
      stress response in calves during umbilical surgery under isoflurane inhalation
      anaesthesia.
AB  - The aim of this study was to examine the effects of preoperative carprofen on the
      cardiorespiratory, hormonal and metabolic stress response during umbilical
      surgery under isoflurane anaesthesia combined with local anaesthesia, in calves.
      A randomised, blinded experimental study was conducted in 24 calves. Carprofen (n
      = 12; 1.4 mg/kg) or physiological saline solution (controls; n = 12) was
      administered 1 h prior to surgery. Anaesthesia was induced with xylazine (0.1
      mg/kg, IM) and, after the onset of sedation (i.e. after 5-8 min), ketamine was
      administered (2 mg/kg, IV). Anaesthesia was then maintained with isoflurane (ISO)
      in oxygen to effect and completed by infiltration of the incision line with 20 mL
      of 2% procaine. Cardiorespiratory, endocrine and metabolic parameters were
      examined before, during and after surgery at short intervals. In both groups,
      anaesthesia appeared adequate for the surgical intervention. Heart rate, stroke
      index and arterial blood pressure were significantly elevated after the onset of
      surgery. Oxygen partial pressure and oxygen delivery increased, while the oxygen
      extraction ratio decreased intraoperatively, ensuring sufficient oxygen supply.
      In the control group, the mean surge in serum cortisol concentrations tended to
      be higher (P = 0.089) and systemic vascular resistance (SVR) was significantly
      greater (P <0.05) than in the carprofen group during surgery. In conclusion, the
      anaesthetic protocol used in this study induced reliable analgesia in both
      groups. The lower serum cortisol levels and SVR may indicate a reduced surgical
      stress response in calves undergoing umbilical surgery under ISO anaesthesia
      after administering carprofen preoperatively. 

PMID- 27687922
TI  - Elimination of virulent strains (aprV2) of Dichelobacter nodosus from feet of 28
      Swiss sheep flocks: A proof of concept study.
AB  - Virulent ovine footrot caused by Dichelobacter nodosus is an endemic disease
      worldwide. It is associated with severe pain, impaired animal welfare and
      economic losses. The competitive real-time PCR for the differentiation of
      virulent aprV2 and benign aprB2 strains of Dichelobacter nodosus provides an
      objective, rapid and sensitive diagnostic tool for footrot surveillance,
      especially as it enables early detection of subclinical carriers of virulent
      strains. The aim of this study was to evaluate the feasibility of complete
      elimination of Dichelobacter nodosus strains carrying the aprV2 gene from sheep
      flocks. The treatment protocol was based on careful removal of loose and severely
      overgrown claw horn, weekly stand-in foot baths of the entire flock for 10 min
      per sheep, using a 10% zinc sulphate disinfectant solution, clinical and PCR
      follow-up and isolation or culling of non-responders. Dichelobacter nodosus
      strains carrying the aprV2 gene were successfully eliminated from the feet of the
      sheep of all 28 flocks (100%) participating in the study within 6-19 weeks of
      weekly foot bathing. A strong correlation between the length of time for weekly
      foot bathing to eliminate the virulent strains and the within-flock prevalence of
      clinical footrot at the beginning was observed (rho, 0.68; P <0.001). A
      statistically significant correlation was not detected between flock size and the
      length of time for weekly foot bathing (rho, 0.28; P = 0.14), or the prevalence
      of clinical footrot at study commencement (rho, -0.04; P = 0.82), respectively.
      In conclusion, a complete elimination of Dichelobacter nodosus strains carrying
      the aprV2 gene in sheep flocks was possible with a protocol based on careful
      trimming, weekly stand-in foot baths, and identification of infection using a
      specific PCR-test and isolation or culling of non-responders. 

PMID- 27687923
TI  - Diagnostic accuracy of a smartphone electrocardiograph in dogs: Comparison with
      standard 6-lead electrocardiography.
AB  - The diagnostic accuracy of a smartphone electrocardiograph (ECG) in evaluating
      heart rhythm and ECG measurements was evaluated in 166 dogs. A standard 6-lead
      ECG was acquired for 1 min in each dog. A smartphone ECG tracing was
      simultaneously recorded using a single-lead bipolar ECG recorder. All ECGs were
      reviewed by one blinded operator, who judged if tracings were acceptable for
      interpretation and assigned an electrocardiographic diagnosis. Agreement between
      smartphone and standard ECG in the interpretation of tracings was evaluated.
      Sensitivity and specificity for the detection of arrhythmia were calculated for
      the smartphone ECG. Smartphone ECG tracings were interpretable in 162/166 (97.6%)
      tracings. A perfect agreement between the smartphone and standard ECG was found
      in detecting bradycardia, tachycardia, ectopic beats and atrioventricular blocks.
      A very good agreement was found in detecting sinus rhythm versus non-sinus rhythm
      (100% sensitivity and 97.9% specificity). The smartphone ECG provided tracings
      that were adequate for analysis in most dogs, with an accurate assessment of
      heart rate, rhythm and common arrhythmias. The smartphone ECG represents an
      additional tool in the diagnosis of arrhythmias in dogs, but is not a substitute
      for a 6-lead ECG. Arrhythmias identified by the smartphone ECG should be followed
      up with a standard ECG before making clinical decisions. 

PMID- 27687924
TI  - Evaluation of three competitive ELISAs and a fluorescence polarisation assay for
      the diagnosis of bovine brucellosis.
AB  - Bovine brucellosis is an infectious disease of worldwide public health and
      economic importance. The usual tests for the diagnosis of this disease include
      the Rose-Bengal test (RBT), complement fixation test (CFT), serum agglutination
      test (SAT) and indirect ELISA. New tests such as competitive ELISAs (C-ELISA) and
      fluorescence polarisation assay (FPA) have been developed. However, C-ELISA may
      correspond to different protocols and a wide variation may exist in their
      diagnostic performance. The aim of this study was to evaluate three commercially
      available C-ELISA kits (C-ELISA1-3) and FPA for the diagnosis of bovine
      brucellosis and compare test performance with RBT, CFT, indirect ELISA and FPA.
      Sera submitted to EU laboratories in 2011 from 5111 adult cattle were tested.
      Individual test sensitivities (Se) and specificities (Sp) were estimated.
      Threshold assessment using the receiver operating characteristic method was also
      performed. The most sensitive tests were FPA (99.0%; 95% confidence interval
      [CI], 97.9-100%), C-ELISA1 (98.4%; 95% CI, 97.0-99.8%) and RBT (97.7%; 95% CI,
      95.9-99.3%). The most specific tests were CFT (99.98%; 95% CI, 99.93-100%), SAT
      (99.98%; 95% CI, 99.93-100%) and RBT (99.89%; 95% CI, 99.79-99.99%). Among the
      new tests, none of the three C-ELISA kits studied could be recommended as a
      single screening test because of their low specificity, especially when used in a
      herd. C-ELISA3 could not be recommended as confirmatory test on individual
      animals to determine whether false positive serological test results had
      occurred. 

PMID- 27687925
TI  - Quantitative analysis of infiltrating immune cells and bovine papillomavirus type
      1 E2-positive cells in equine sarcoids.
AB  - Sarcoids are the most frequently observed skin tumours in equids and consist of
      cutaneous accumulations of transformed fibroblasts. Their aetiopathogenesis is
      closely linked to a presumably abortive infection by bovine papillomavirus (BPV)
      types 1 and 2. In cattle, dermal fibropapillomas induced by BPV1/2 usually
      regress spontaneously due to a local, cell-mediated, immune response; however,
      equids appear to lack an effective immune response to BPV1/2 and mechanisms of
      immune evasion have been postulated. As a consequence, equine sarcoids tend to
      persist and are prone to recur. In this study, cryosections were analysed by
      immunofluorescent staining and a high content analysis system to determine the
      presence and distribution of CD4(+), CD8(+), FoxP3(+), RORgammat(-), CD206(+) and
      CD14(+) cells, along with expression of the BPV1 early regulatory protein E2. A
      higher density of cells was positive for BPV1 E2(+) within the transformed tissue
      than in perilesional tissue or normal skin of horses with sarcoids and control
      horses. The proportion of CD8(+) cytotoxic T cells was significantly increased in
      perilesional and lesional tissues, whereas CD4(+) T helper cells were present in
      higher density only in lesional tissue compared to normal skin from horses with
      and without sarcoids. The proportion of pro-inflammatory
      CD4(+)FoxP3(+)RORgammat(+) regulatory T cells was decreased in sarcoid tissue
      compared to perilesional, distant and control tissue. There were no significant
      differences in densities of CD4(+)FoxP3(+) RORgammat(-) regulatory T cells
      between sarcoids and control tissues. Equine sarcoids are characterised by
      infiltrations of CD8(+) and CD4(+) T cells, with decreased representation by pro
      inflammatory CD4(+)FoxP3(+)RORgammat(+) regulatory T cells. 

PMID- 27687926
TI  - A novel set of behavioural indicators for measuring perception of food by cats.
AB  - Behavioural indicators provide a promising approach for objective assessment of
      the perceptions of animals. In cats, the frequency of specific behaviours as
      indicators of perception has been studied in connection with food palatability.
      The aim of this study was to expand that knowledge by identifying behavioural
      indicators correlating with three degrees of palatability. Thirty-four pet cats
      were presented with three types of items: favoured food (FF), favoured food with
      a placebo mini-tablet hidden inside (TFF) and non-favoured food (NFF). The items
      were presented in a pseudo-randomised sequence, with six trials per item and 18
      trials per cat. The behaviour of cats before, during and after eating, or
      refusing to eat, was video-recorded. Two trained observers, blinded to the types
      of food items, independently determined the frequency of 16 behavioural patterns
      on the video recordings. The data were analysed using a mixed logistic regression
      model. Five behavioural patterns differentiated FF from NFF; 'flick ears
      backwards', 'lick nose, not eaten', 'flick tail' and 'groom body' were more
      frequent with NFF, whereas 'lick lips' was more frequent with FF. One indicator,
      'drop item', was more frequent with TFF than FF. These findings provide evidence
      of new behavioural indicators for objective assessment of food perception in
      cats. The findings also have practical applicability in designing a novel
      palatability test to be utilised in developing veterinary pharmaceuticals with
      improved palatability for cats. 

PMID- 27687927
TI  - Existence of bovine neonatal pancytopenia before the year 2005? Retrospective
      evaluation of 215 cases of haemorrhagic diathesis in cattle.
AB  - Haemorrhagic diathesis (HD) in cattle is a relatively rare syndrome that can have
      many different causes. With the occurrence of bovine neonatal pancytopenia (BNP)
      in 2007, the number of cases of HD in cattle has increased. This led to an
      enhanced interest in diseases presenting with bleeding disorders. The possible
      causes of HD in cattle, the clinical findings, and the course of various diseases
      are described and evaluated. Furthermore, we determined whether cases of BNP
      occurred before the introduction of the vaccine Pregsure BVD since its widespread
      use was associated with the syndrome. Records of 215 cases of HD in cattle that
      had been referred to the Clinic for Ruminants with Ambulatory and Herd Health
      Services at the Centre for Clinical Veterinary Medicine, Ludwig Maximilian
      University, Munich, between 1982 and 2014 were evaluated. The two most commonly
      diagnosed diseases were BNP (n = 95) and septicaemia (n = 35), with fatality
      rates of 82% and 66%, respectively. In 27 (13%) cases, no clear cause for the HD
      could be designated. Statistically significant differences were found with regard
      to the course of the various disorders and the clinical findings. A receiver
      operating characteristic analysis of thrombocyte counts of affected animals at
      the time of arrival at the clinic did not provide any predictive information on
      disease outcome. Two cases of HD occurred before the introduction of Pregsure BVD
      (1989, 1991). In both cases, clinical, haematological, and pathological findings
      were identical to BNP. The cause of HD in these two cases could not be determined
      retrospectively. 

PMID- 27687928
TI  - Bovine spastic paresis: A review of the genetic background and perspectives for
      the future.
AB  - Bovine spastic paresis (BSP) is a sporadic, progressive neuromuscular disease
      that is thought to affect all breeds of cattle. The disease manifests as a
      unilateral or bilateral hyperextension of the hind limb due to increased muscle
      tone or permanent spasm of mainly the gastrocnemius and/or the quadriceps muscle.
      Clinical signs only appear in rising, standing and moving animals, which is an
      important diagnostic feature. Although several medical treatments have been
      described, surgical procedures such as neurectomy or tenectomy are generally
      indicated. Even though complete recovery can be achieved, BSP-affected animals
      should not be used for breeding, since BSP is commonly considered a hereditary
      disease. The condition therefore negatively affects animal welfare, economics and
      breeding. When first described in 1922, BSP was already assumed to be heritable,
      and this assumption has been perpetuated by subsequent authors who have only
      discussed its possible modes of inheritance, which included monogenetic and
      polygenetic modes and gene-environment interactions. Besides some clinical
      aspects and the consideration of the tarsal joint angle as a BSP-correlated
      trait, this review mainly focuses on the assumed genetic aspects of BSP.
      Evaluation of the published literature demonstrates that to date, irrevocable
      proof for the assumed heritability of BSP is still missing. The assumption of
      heredity is further contradicted by known allele frequencies and incidences of
      proven hereditary diseases in cattle, such as arachnomelia or bovine spinal
      muscular atrophy. Consequently, future research is needed to determine the cause
      of spastic paresis. Procedures that will help test the null-hypothesis ('BSP is
      not hereditary') and possible modes of inheritance are discussed in this review. 

PMID- 27687929
TI  - Serum biochemistry profile, inflammatory cytokines, adipokines and cardiovascular
      findings in obese dogs.
AB  - The aim of this study was to evaluate the serum biochemistry profile,
      inflammatory cytokines, adipokines and cardiovascular findings in obese dogs.
      Twenty obese and 20 normal weight healthy pet dogs were recruited into the study,
      where they underwent blood testing and assessment of cardiovascular function
      (blood pressure analysis, electrocardiography and echocardiography). Higher
      concentrations of total cholesterol, triglycerides, lactate dehydrogenase, total
      serum proteins, alpha-globulins, total bilirubin, insulin, insulin:glucose ratio,
      alkaline phosphate and alanine aminotransferase were observed in obese dogs than
      dogs of normal weight. There were no differences in concentrations of tumour
      necrosis factor (TNF)-alpha or interleukin (IL)-6 between the two groups. Obese
      dogs had higher serum leptin but lower adiponectin concentrations than dogs of
      normal weight. Systolic arterial blood pressure was higher in obese dogs than
      dogs of normal weight. The values for the thickness of the free wall of the left
      ventricle and interventricular septal thickness were greater at end-diastole in
      obese dogs compared to dogs of normal weight. Four of 20 obese dogs were
      determined to have obesity-related metabolic dysfunction (ORMD). The findings
      indicate that a chronic inflammatory state is not necessarily evident in obese
      dogs, as has been described in human beings, and the criteria used for ORMD can
      be used to define this syndrome in dogs. In this study, canine obesity was
      associated with cardiac and vascular dysfunction. 

PMID- 27687930
TI  - Challenging conventional wisdom with vigour.

PMID- 27687931
TI  - Claw health and prevalence of lameness in cows from compost bedded and cubicle
      freestall dairy barns in Austria.
AB  - Claw health and lameness data from five dairies with compost bedded barns (n =
      201 data sets) were evaluated and compared with data from five dairy herds housed
      in freestall cubicle barns (n = 297 data sets). They were matched for having the
      same cow numbers, flooring type and similar milk yield. The prevalence of
      lameness, claw lesions and their severity grades were analysed. Two claw health
      indicators, the cow claw score (CCS) and the farm claw score (FCS), were
      calculated using a computerised claw trimming database programme; there was no
      significant difference in overall lameness prevalence in cows from five compost
      bedded barns (18.7%) compared to cows from five freestall cubicle herds (14.9%).
      A cumulative link mixed model (CLMM) did not show significant differences in
      locomotion between different types of bedding material, flooring system, breed,
      visit number, observer and time since last trimming, but locomotion was
      significantly influenced by CCS. Another CLMM tested the impact of parameters
      mentioned on CCS and showed significant influence of flooring type, visit number
      and cattle breed. Statistically significant differences in the prevalence of claw
      disorders between compost bedded and freestall cubicle barns were found for white
      line disease (WLD; 20.4% and 46.6%, respectively), heel horn erosion (HHE; 26.9%
      and 59.9%, respectively), concave dorsal wall as a result of chronic laminitis
      (6.5% and 15.9%, respectively) and for interdigital hyperplasia (0.2% and 3.1%,
      respectively). The results of this study indicate that compost dairy barns are a
      good alternative to common cubicle housing systems in terms of lameness, claw
      health and animal welfare. 

PMID- 27687932
TI  - Bioluminescent avian pathogenic Escherichia coli for monitoring colibacillosis in
      experimentally infected chickens.
AB  - Avian pathogenic Escherichia coli (APEC) are responsible for significant economic
      losses in the poultry industry. In this study, a model for investigating the
      pathogenesis of APEC infections was established. APEC strain CH2 (O78) was marked
      with the luciferase operon (luxCDABE) using a Tn7 transposon and tissues of
      experimentally infected chickens were analysed for a correlation between the
      bioluminescent signal and the number of bacteria. Transposition of the lux operon
      into the chromosome of the APEC isolate did not affect sensitivity to lytic
      bacteriophages and there was no effect on virulence in an intratracheal infection
      model in 1-day-old chicks, although results with a subcutaneous infection model
      were inconclusive. A correlation between the number of bacteria and the
      luminescent signal was found in liquid medium, as well as in homogenised heart,
      liver, spleen and lung of 4-week-old experimentally infected chickens. This study
      showed that lux could be used for identification of the infecting strain after
      experimental infection with APEC in poultry. 

PMID- 27687933
TI  - Controlled trial of whole body protein synthesis and plasma amino acid
      concentrations in yearling horses fed graded amounts of lysine.
AB  - Lysine has been reported as the first limiting amino acid in typical equine
      diets. Indicator amino acid oxidation (IAAO) has become the standard method for
      determining amino acid requirements in other species, but prior to this study, it
      has not been used to determine equine requirements. The aim of this study was to
      evaluate whole body protein synthesis and plasma and muscle amino acid
      concentrations in response to graded levels of lysine intake in yearling horses.
      Six Thoroughbred colts (358 +/- 5 kg) were fed each of six treatment lysine
      intakes ranging from 76 to 136 mg/kg body weight/day. Blood samples were taken
      before and 90 min after the morning concentrate meal. Gluteal muscle biopsies
      were taken ~100 min after the morning concentrate meal. The next day, whole body
      phenylalanine kinetics were determined using a 2 h primed, constant infusion of
      [(13)C] sodium bicarbonate followed by a 6 h primed, constant infusion of [1
      (13)C] phenylalanine. Plasma lysine concentrations increased linearly (P <0.05)
      at both the 0 and 90 min time points with increasing lysine intakes. Free muscle
      asparagine, aspartate, arginine, glutamine, lysine, taurine and tryptophan
      concentrations responded quadratically to lysine intake (P <0.05). Phenylalanine
      kinetics did not differ between treatment intakes (P > 0.10). A broken line
      analysis of lysine intake and phenylalanine oxidation failed to yield a
      breakpoint from which to determine a lysine requirement. These diets may have
      been limiting in an amino acid other than lysine, underscoring the lack of data
      concerning amino acid requirements and bioavailability data in the horse. 

PMID- 27687934
TI  - Distortion product otoacoustic emissions in geriatric dogs.
AB  - Recordings of distortion product otoacoustic emissions (DPOAE) were taken from 28
      geriatric dogs aged 12.2 +/- 2.2 years and 15 control dogs aged 5.9 +/- 3.0 years
      (mean +/- standard deviation) to demonstrate frequency-specific changes in
      cochlear responses. Recordings were performed for primary frequencies of 2-12 kHz
      in 2 kHz increments. Brainstem auditory evoked response (BAER) recordings were
      also made from geriatric dogs for comparison with DPOAE responses. Significant
      decreases in DPOAE response amplitudes were observed at frequencies of 6-12 kHz
      in geriatric dogs compared to control dogs, reflecting loss of cochlear outer
      hair cells along the length of the cochlea. Significant decreases in response
      amplitudes were not seen at frequencies of 2 or 4 kHz. Decreases in BAER response
      amplitudes subjectively paralleled the depressed DPOAE amplitudes. No significant
      linear regression relationships were found for DPOAE response amplitude vs. age
      despite the progressive nature of age-related hearing loss. The reductions in
      response at all frequencies starting at the age where dogs are considered
      geriatric indicate that age-related hearing loss begins earlier in the life span.
      DPOAE recordings provide a means to assess cochlear function across different
      portions of the auditory spectrum for assessing hearing loss associated with
      aging, and potentially for losses from other causes of decreased auditory
      function. 

PMID- 27687935
TI  - Immune response to bovine papillomavirus type 1 in equine sarcoid.

PMID- 27687936
TI  - Distribution of feline lymphoma in the central and peripheral nervous systems.
AB  - In cats, lymphoma (lymphosarcoma) is the most common neoplasm affecting the
      spinal cord and the second most common intracranial tumour. Although lymphoma
      commonly develops in the spinal cord as a part of a multicentric process, a
      primary form may occur. Lymphoma can exhibit a wide range of morphological
      patterns, including intraparenchymal brain mass, lymphomatosis cerebri,
      intravascular lymphoma, lymphomatous choroiditis and meningitis, extradural,
      intradural-extramedullary or intramedullary lymphoma in the spinal cord, or
      neurolymphomatosis in the peripheral nerves. Lymphoma may occur as a
      paraneoplastic disorder associated with peripheral neuropathies. Magnetic
      resonance imaging (MRI) and computed tomography (CT) are the techniques of choice
      for morphological assessment of nervous system lesions in vivo. However, biopsy
      should be performed to achieve a definitive diagnosis. Knowledge of the different
      morphological patterns expressed by lymphoma in the nervous system of cats allows
      veterinary clinicians to suspect lymphoma and to arrange appropriate diagnostic
      procedures, including immunophenotype and clonality studies, along with
      therapeutic protocols and prognostic evaluations. 

PMID- 27687937
TI  - Prevalence and antimicrobial susceptibility of bacterial isolates from horses
      with synovial sepsis: A cross-sectional study of 95 cases.
AB  - Bacterial culture and antimicrobial susceptibility testing of septic synovial
      samples allows instigation of targeted antimicrobial therapy; however, bacterial
      culture takes more than 24 h and has low sensitivity. This study aimed to
      identify the most frequently cultured bacteria and their antimicrobial
      susceptibility profile from septic synovial samples in our referral equine
      hospital, to allow recommendations regarding appropriate initial antimicrobial
      therapy prior to culture results. Hospital records for all horses with synovial
      sepsis and a synovial sample submitted to the microbiology laboratory between
      2004 and 2013 were retrieved (n= 379 samples). One horse had positive cultures
      from more than one synovial structure, and two horses had positive cultures
      obtained from repeat samples. Overall, 114 bacterial isolates were obtained. Gram
      positive bacteria were isolated in 75% of cases, of which 22% were haemolytic
      Staphylococcus spp., and 52% were Staphylococcus aureus including two multidrug
      resistant isolates. Gram-negative bacteria were isolated from 25% of cases.
      Anaerobic Clostridium spp. was isolated in 3% of cases. Of the first line
      antimicrobials, oxytetracycline and doxycycline were effective against 70-100% of
      the Gram-positive bacteria and 20-100% of the Gram-negative organisms, whilst
      trimethoprim-sulphamethoxazole and gentamicin efficacy ranged between 50% and 88%
      for both Gram-positive and Gram-negative bacteria. Of the equine protected
      antimicrobials, ceftiofur was effective against 70-90% of all bacterial isolates
      whilst 80% of isolates were susceptible to enrofloxacin. These results indicate
      that tetracyclines, trimethoprim-sulphamethoxazole or gentamicin may be suitable
      first-line antimicrobials for treatment of synovial sepsis cases while awaiting
      laboratory results, findings which support current recommendations for
      antimicrobial stewardship in equine medicine. 

PMID- 27687938
TI  - Expression of microRNAs miR-21 and miR-181c in cerebrospinal fluid and serum in
      canine meningoencephalomyelitis of unknown origin.
AB  - The potential of microRNAs (miRNAs) as biomarkers for canine
      meningoencephalomyelitis of unknown origin (MUO) was investigated by using
      quantitative real-time (qRT)-PCR to determine the expression of microRNA-21 (miR
      21) and microRNA-181c (miR-181c) in the cerebrospinal fluid (CSF) of dogs. Dogs
      with MUO (n = 10) had higher levels of expression of miR-21 and miR-181c in the
      CSF than dogs with non-inflammatory neurological diseases (n = 8). There was a
      positive correlation between CSF cellularity and expression of miRNAs in the CSF,
      particularly for miR-21 in the MUO group. 

PMID- 27687939
TI  - Equine atypical myopathy: A metabolic study.
AB  - Atypical myopathy (AM) is a potentially fatal disease of grazing horses. It is
      reportedly caused by the ingestion of sycamore seeds containing toxic hypoglycin
      A. In order to study metabolic changes, serum and urine samples from nine horses
      with atypical myopathy and 12 control samples from clinically healthy horses were
      collected and then analysed using a high-performance liquid chromatography
      coupled with tandem mass spectrometry; serum metabolic profiles as the disease
      progressed were also studied. Metabolic data were evaluated using unsupervised
      and supervised multivariate analyses. Significant differences were demonstrated
      in the concentrations of various glycine conjugates and acylcarnitines (C2-C26).
      Moreover, the concentrations of purine and pyrimidine metabolites, vitamins and
      their degradation products (riboflavin, trigonelline, pyridoxate, pantothenate),
      and selected organic and amino acids (aspartate, leucine, 2-oxoglutarate, etc.)
      were altered in horses with AM. These results represent a global view of altered
      metabolism in horses with atypical myopathy. 

PMID- 27687940
TI  - Detection of Yersinia enterocolitica serotype O:9 in the faeces of cattle with
      false positive reactions in serological tests for brucellosis in Ireland.
AB  - Intestinal infection by Yersinia enterocolitica serotype O:9 (YeO9) in cattle has
      been linked to false positive serological reactivity (FPSR) in diagnostic tests
      for brucellosis. Although eradicated in Ireland, brucellosis monitoring still
      identifies seropositive animals, usually one or two (termed singletons) per herd,
      which are classed as FPSR. To investigate a link between FPSR and YeO9, faeces
      and blood were collected from singleton FPSR cattle, and from companion animals,
      in eight selected herds with more than one FPSR animal, for YeO9 culture and
      Brucella serology. YeO9 was isolated from 76/474 (16%) FPSR singletons in 309
      herds, but not from any of 621 animals in 122 control non-FPSR herds. In the FPSR
      herds 52/187 (27.8%) animals were culture positive, and 17% of the isolates were
      from seronegative animals. Seropositive animals were more likely to have a rising
      antibody titre when culture positive. 

PMID- 27687941
TI  - Differential secretion of adipokines from subcutaneous and visceral adipose
      tissue in healthy dogs: Association with body condition and response to
      troglitazone.
AB  - This study aimed to determine the effects of body condition, fat depot, and a
      peroxisome proliferator-activated receptor gamma-agonist (troglitazone) on
      secretion of adiponectin, interleukin-6 (IL6), and tumor necrosis factor-alpha
      (TNFalpha) from adipose tissue of healthy dogs. Subcutaneous and omental visceral
      adipose tissue samples were collected from 16 healthy intact female dogs, and
      body condition score (range 4-8/9) was determined. Concentrations of adiponectin
      were measured in mature adipocytes cultures and concentrations of IL6 and
      TNFalpha were measured in stromovascular cells cultures after 48 h incubation in
      fresh control medium, or fresh medium containing 10 uM troglitazone. Mature
      adipocytes and stromovascular cells of subcutaneous origin secreted higher
      concentrations of adiponectin and lower concentration of IL6 and TNFalpha,
      respectively, than corresponding cells of visceral origin, in both the control (P
      = 0.015, P = 0.004, and P = 0.016, respectively) and troglitazone-treated
      cultures (P <0.001, P = 0.004, and P = 0.016, respectively). Troglitazone
      increased adiponectin secretion from mature adipocytes in visceral (P = 0.019),
      but not in subcutaneous fat cultures (P = 0.4). Troglitazone decreased IL6 and
      TNFalpha secretion from stromovascular cells both in visceral (P = 0.047 and P =
      0.016, respectively) and subcutaneous (P = 0.047 and P = 0.016, respectively) fat
      cultures. Higher body condition score was associated with lower secretion of
      adiponectin from mature adipocytes (P = 0.007), lower secretion of IL6 (P =
      0.040) and higher secretion of TNFalpha (P = 0.040) from stromovascular cells.
      This study showed differential secretion of adipokines by subcutaneous and
      visceral fat depots in dogs and association between body condition and adipokine
      secretion. Activation of PPARgamma altered adipokine secretion. 

PMID- 27687942
TI  - Mycoplasma mastitis in cattle: To cull or not to cull.
AB  - Bovine mastitis caused by mycoplasmas, in particular Mycoplasma bovis, is a major
      problem for milk production and animal welfare in large dairy herds in the USA
      and a serious, although sporadic, disease in Europe and the Middle East. It
      causes severe damage to the udder of cattle and is largely untreatable by
      chemotherapy. Mycoplasma mastitis has a distinct epidemiology and a unique set of
      risk factors, the most important of which is large herd size. The disease is
      often self-limiting, disappearing within months of outbreaks, sometimes without
      deliberate intervention. Improved molecular diagnostic tests are leading to more
      rapid detection of mycoplasmas. Typing tests, such as multi-locus sequence
      typing, can help trace the source of outbreaks. An approach to successful control
      is proposed, which involves regular monitoring and rapid segregation or culling
      of infected cows. Serious consideration should be given by owners of healthy
      dairy herds to the purchase of M. bovis-free replacements. Increased cases of
      disease could occur in Europe and Israel if the trend for larger dairy herds
      continues. 

PMID- 27687943
TI  - T-cell factor-4 and MHC upregulation in pigs receiving a live attenuated
      classical swine fever virus (CSFV) vaccine strain with interferon-gamma adjuvant.
AB  - The effect of co-administration of interferon (IFN)-gamma in pigs undergoing
      vaccination with an attenuated strain (LPC) of classical swine fever virus (CSFV)
      was investigated. Unvaccinated pigs demonstrated pyrexia and died 7-9 days after
      challenge with virulent CSFV. Pigs receiving the attenuated vaccine remained
      healthy after virus challenge, except for mild, transient pyrexia, whereas pigs
      receiving IFN-gamma simultaneously with the vaccine demonstrated normal body
      temperatures after virus challenge. Examination by nested RT-PCR revealed greater
      viral load in the spleens of the pigs vaccinated with the attenuated CSFV,
      compared with those that had additionally received IFN-gamma. Expression of major
      histocompatibility complex (MHC) class I and MHC class II molecules was
      upregulated in the spleens of the IFN-gamma treated vaccinated pigs, demonstrated
      by immunohistochemistry. Based on Western blot analysis, anti-CSFV IgG2
      antibodies were elevated in vaccinated pigs by co-administration of IFN-gamma
      (IFN-gamma(Hi): P < 0.01; IFN-gamma(Lo): P <0.05). By employing the suppression
      subtractive hybridization technique, RT-PCR, in situ hybridization, and
      immunohistochemistry, T-cell factor-4 (Tcf-4) mRNA and protein expression were
      found to be upregulated in the spleens of vaccinated pigs that had received IFN
      gamma. This study suggests involvement of Tcf-4 in IFN-gamma-mediated immune
      regulation following CSFV vaccination. 

PMID- 27687944
TI  - Comparison of treatment outcomes for superficial digital flexor tendonitis in
      National Hunt racehorses.
AB  - Superficial digital flexor (SDF) tendonitis is a common injury in Thoroughbred
      racehorses. Injuries require prolonged rehabilitation, with unpredictable
      outcomes and a high incidence of re-injury. This observational case-control study
      aimed to compare race outcomes after commonly advocated treatments for tendon
      healing. Clinical and racing records were evaluated for 127 National Hunt
      racehorses treated between 2007 and 2011 for an SDF tendon injury. Two age- and
      sex-matched control horses were selected for each case horse to analyse the
      effect on post-injury racing outcomes of pre-injury data, lesion severity and
      treatment group [controlled exercise alone, bar firing, intralesional platelet
      rich plasma (PRP), tendon splitting, tendon splitting combined with bar firing].
      Control horses raced more often than case horses, with higher maximum racing post
      rating (RPRmax) and longer racing distances. Pre-injury racing performance was
      not associated with treatment group. Rate of return to racing was not associated
      with lesion severity or treatment group. Number of races, total distance raced
      post-injury and RPRmax were not associated with lesion severity or treatment
      group. Controlled exercise alone offered similar post-injury racing outcomes in
      National Hunt racehorses with SDF tendonitis to the other treatment options
      examined. Bar firing, either alone or in conjunction with tendon splitting,
      provided no additional benefit in rate of return to racing and race performance. 

PMID- 27687945
TI  - Management factors associated with mortality of dairy calves in Finland: A cross
      sectional study.
AB  - Mortality at herd level is an indicator of overall calf welfare on dairy farms.
      The aim of this cross sectional study was to identify management factors
      associated with calf mortality on dairy farms in Finland. Calf mortality data and
      information on management practices collected during farm visits and farmer
      interviews were analysed using linear models. The average size of 82 herds
      enrolled in the study was 125 +/- 41 cows. The mortality risk of calves <7 days
      of age was 5 (or 5.2) +/- 2.3% and was associated with larger herd size and the
      practice of not separating sick calves from other calves (6.0 +/- 0.4 vs. 4.7 +/-
      0.3%; P < 0.05). The mortality risk of calves aged 7-180 days was 6 (or 5.7) +/-
      6.2% and increased with a shorter whole milk feeding period, longer period in the
      calving pen and lower average herd production level (P < 0.05). The mortality
      risk of calves was lower on farms where a veterinarian disbudded calves instead
      of farmer. Longer milk feeding and improved management of sick calves are
      recommended to reduce calf mortality. Specific management practices associated
      with lower mortality risk should be emphasised when advising farmers on how to
      enhance calf welfare. 

PMID- 27687947
TI  - Corrigendum to 'Variance associated with use of relative velocity for force
      platform gait analysis in a heterogeneous population of clinically normal dogs'
      [The Veterinary Journal 207 (2016) 80-84].

PMID- 27687946
TI  - Evaluation of different sampling methods and criteria for diagnosing canine
      urinary tract infection by quantitative bacterial culture.
AB  - The use of voided urine specimens for bacteriological culture in dogs is
      discouraged because contamination from external genitalia could lead to
      misinterpretation of laboratory results. Quantitative culturing and defining
      significant bacteriuria could increase the usefulness of voided specimens.
      However, limited evidence exists for the cut-offs currently recommended. The aim
      of this study was to evaluate the accuracy of current veterinary cut-off values
      for significant bacteriuria in voided canine urine. A secondary aim was to
      investigate if accuracy improved when applying qualitative criteria used in
      humans. Paired urine specimens were collected by both cystocentesis and voiding,
      and quantitative bacteriological cultures were performed within the same day.
      Cystocentesis was used as the reference standard with a cut-off for significant
      bacteriuria of >=1000 colony forming units (CFU)/mL. Voided specimens were
      compared to cystocentesis using: (1) the veterinary cut-off of >=100,000 CFU/mL;
      and (2) various cut-offs depending on qualitative criteria (sex, clinical signs
      and complicating factors), adapted from human guidelines. Ninety-four dogs with
      suspected urinary tract infection (UTI) were included for analysis. The
      veterinary cut-off yielded an accuracy of 94% with a sensitivity and specificity
      of 94% (95% confidence intervals [CI] 0.81, 0.99) and 94% (95% CI 0.86, 0.98),
      respectively. Applying the human guidelines did not improve overall accuracy
      (89%), and yielded a sensitivity and specificity of 97% (95% CI 0.86, 1.00) and
      86% (95% CI 0.77, 0.92), respectively. The veterinary cut-off value of >=100,000
      CFU/mL for voided urine is appropriate for determining significant bacteriuria in
      the majority of dogs with suspected UTI if specimens are refrigerated and
      cultured on the day of collection. 

PMID- 27687948
TI  - Monitoring acute equine visceral pain with the Equine Utrecht University Scale
      for Composite Pain Assessment (EQUUS-COMPASS) and the Equine Utrecht University
      Scale for Facial Assessment of Pain (EQUUS-FAP): A validation study.
AB  - This study presents the validation of two recently described pain scales, the
      Equine Utrecht University Scale for Composite Pain Assessment (EQUUS-COMPASS) and
      the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP), in
      horses with acute colic. A follow-up cohort study of 46 adult horses (n = 23 with
      acute colic; n = 23 healthy control horses) was performed for validation and
      refinement of the constructed scales. Both pain scales showed statistically
      significant differences between horses with colic and healthy control horses, and
      between horses with colic that could be treated conservatively and those that
      required surgical treatment or were euthanased. Sensitivity and specificity were
      good for both EQUUS-COMPASS (87% and 71%, respectively) and EQUUS-FAP (77% and
      100%, respectively) and were not substantially influenced by applying weighting
      factors to the individual parameters. 

PMID- 27687949
TI  - Motor evoked potentials in standing and recumbent calves induced by magnetic
      stimulation at the foramen magnum.
AB  - The aims of this study were to determine reference values for magnetic motor
      evoked potentials (mMEPs) in calves and the influence of position during
      examination (standing or lateral recumbency). Reference values were determined
      using 41 healthy Holstein Friesian bull calves aged 1-10 months; standing and
      lateral recumbency were examined in 11 calves. Maximal magnetic stimulation was
      performed at the level of the foramen magnum with a magnetic field of 4 T at the
      coil surface. In standing position, distinct, reproducible mMEPs were obtained in
      all calves. Onset latency (LAT) (mean +/- standard deviation) was significantly
      shorter in the thoracic limbs (34.4 +/- 3.1 ms) than in the pelvic limbs (44.6 +/
      3.0 ms). Amplitude (AMPL) was significantly higher in the thoracic limbs (3.7 +/
      1.7 mV) than in the pelvic limbs (3.3 +/- 1.7 mV) and significantly increased
      with body length. Age, body weight, height at the withers and rectal temperature
      had no significant association with LAT or AMPL, and no differences between left
      and right were noted. In the lateral position, only 64% of the calves showed
      responses in the four limbs; in these calves, LAT (29.7 +/- 4.7 ms) and AMPL (3.0
      +/- 1.8 mV) in the thoracic limbs were significantly different from AMPL (47.0 +/
      7.4 ms) and LAT (2.1 +/- 2.1 mV) in the pelvic limbs. In conclusion, mMEPs in
      limb muscles can be evoked in calves by stimulation at the level of the foramen
      magnum. mMEPs are more difficult to obtain in lateral recumbency than in standing
      calves. 

PMID- 27687950
TI  - Isolation and characterisation of peripheral blood-derived feline mesenchymal
      stem cells.
AB  - The aim of this study was to isolate mesenchymal stem cells (MSCs) from feline
      peripheral blood (fPB-MSCs) and to characterise the cells' in vitro properties.
      The mononuclear cell fractions were isolated from venous blood of cats by density
      gradient centrifugation and cultured on plastic dishes under various culture
      conditions to isolate MSCs. When these cells were cultured with 5% autologous
      plasma (AP) and 10% foetal bovine serum (FBS), adherent spindle shaped fibroblast
      like cells (fPB-MSCs) were obtained from 15/22 (68%) cats. These cells were
      isolated only from medium containing both AP and FBS. The morphology of these
      MSCs was similar to those isolated from other species and from other feline
      tissues. fPB-MSCs expanded steadily up to 5-6 passages, but had increased
      population doubling time during passaging and almost all cells stopped
      proliferation at passages 7-9. These cells expressed CD44 and CD90, and were
      mostly negative for major histocompatibility class II and CD4. The cells could be
      induced to differentiate into adipogenic, osteogenic and chondrogenic cell
      lineages. These findings indicate that fPB-MSCs can be generated but appear to
      require specific culture conditions. 

PMID- 27687951
TI  - Inter-observer agreement for clinical examinations of foot lesions of sheep.
AB  - In sheep, the diagnosis of foot lesions is routinely based on physical
      examination of the hoof. Correct diagnosis is important for the effective
      treatment, prevention and control of both infectious and non-infectious causes of
      lameness. Therefore, the aim of this study was to evaluate the level of inter
      observer agreement for clinical examination of ovine foot lesions. Eight
      observers of varying experience, training and occupation performed foot
      examinations on a total of 1158 sheep from 38 farms across North England and
      Wales. On each farm, a group of two to four observers independently examined a
      sample of 24 to 30 sheep to diagnose the presence or absence of specific foot
      lesions including white line lesions (WL), contagious ovine digital dermatitis
      (CODD), footrot (FR), inter-digital dermatitis (ID) and toe granuloma (TG). The
      inter-observer agreement of foot lesion assessments was examined using Fleiss
      kappa (kappa), and Cohen's kappa examined the paired agreement between the test
      standard observer (TSO) and each observer. Scoring differences with the TSO were
      examined as the percentage of scoring errors and assessed for evidence of
      systematic scoring bias. With the exception of WL (maximum error rate 33.3%), few
      scoring differences with the TSO occurred (maximum error rate 3.3%). This
      suggests that observers can achieve good levels of reliability when diagnosing
      most of the commonly observed foot conditions associated with lameness in sheep. 

PMID- 27687952
TI  - Clinical, histopathological and metabolic responses following exercise in Arabian
      horses with a history of exertional rhabdomyolysis.
AB  - A previous report suggests a substantial incidence of exertional rhabdomyolysis
      (ER) in Arabian horses performing endurance racing. This study compared formalin
      histopathology and clinical and metabolic responses to a standardised field
      exercise test (SET) between Arabians with and without ER. Arabian horses with (n
      = 10; age 15.4 +/- 5.6 years) and without (n = 9; 12.9 +/- 6.1 years) prior ER
      were stall-rested for 24-48 h, after which paired ER and control horses were
      fitted with a telemetric ECG and performed a 47 min submaximal SET. Plasma
      glucose, lactate, electrolyte and total protein concentrations and packed cell
      volume were measured before and immediately after exercise. Blood and
      percutaneous gluteal muscle samples were also obtained before and 3 h after
      exercise for measurement of plasma creatine kinase (CK) activity and muscle
      glycogen concentration, respectively. Histopathologic analysis of formalin-fixed
      pre-exercise muscle sections was performed. Data were analyzed by ANOVA and non
      parametric tests (P <0.05). No horses displayed clinical signs of ER during
      exercise, and plasma CK increased similarly in ER and control Arabians. Muscle
      glycogen, heart rate, and remaining plasma variables did not differ between
      horses with ER and control horses. Horses with ER had more internalised nuclei in
      mature myofibers, more aggregates of cytoplasmic glycogen and desmin, and higher
      myopathic scores than control horses. Although many horses with ER had
      histopathologic evidence of chronic myopathy, muscle glycogen concentrations and
      metabolic exercise responses were normal. Results did not support a consistent
      metabolic myopathy or a glycogen storage disorder in Arabians with ER. 

PMID- 27687953
TI  - Detection of compressive hydrated nucleus pulposus extrusion in dogs with
      multislice computed tomography.
AB  - Compressive hydrated nucleus pulposus extrusion (HNPE) in dogs is defined as
      acute extradural compression by hydrated nucleus pulposus material at the level
      of the associated intervertebral disc. Magnetic resonance imaging (MRI) is the
      imaging modality of choice for diagnosis of HNPE. The aims of this study were to
      determine the usefulness of unenhanced computed tomography (CT) and contrast
      enhanced CT (CE-CT), and the sensitivity and specificity of CE-CT, for detection
      of compressive HNPE. Using CE-CT, HNPE was visualised as a hypodense extradural
      compressive lesion with rim enhancement immediately dorsal to the intervertebral
      disc space, with a sensitivity of 91% and a specificity of 100%. CE-CT is a
      useful technique to detect compressive HNPE in dogs. However, if no clear lesion
      is identified with CE-CT, or if additional information about intramedullary
      changes is required, MRI still needs to be performed. 

PMID- 27687954
TI  - Molecular epidemiology of senecavirus A associated with vesicular disease in pigs
      in Brazil.
AB  - Senecavirus A (SV-A) may cause vesicular disease and neonatal mortality in pigs,
      and was first detected in Brazil in 2015. Samples including tissues and serum
      from pigs with suspected vesicular diseases were collected from January to August
      in 2015 from farms in the states of Minas Gerais, Santa Catarina, Goias and Rio
      Grande do Sul, Brazil, and tested for the presence of SV-A by reverse
      transcriptase PCR. All samples were negative for foot and mouth disease virus, as
      well as 13 other infectious agents associated with vesicular diseases in pigs. SV
      A was detected by PCR in 65/265 (24.5%) specimens. A 530 base pair fragment
      sequenced from the VP1 protein coding region indicated a high genetic distance
      from SV-A in other countries, but a common origin among the Brazilian isolates. 

PMID- 27687956
TI  - A novel slow-releasing hydrogen sulfide donor, FW1256, exerts anti-inflammatory
      effects in mouse macrophages and in vivo.
AB  - Exogenous hydrogen sulfide (H2S) is known to exert anti-inflammatory effects both
      in macrophages and in animal models. In this study, we first showed that NaHS
      caused a concentration dependent reduction in TNFalpha and IL-6 secretion in LPS
      stimulated RAW264.7 macrophages in the absence of cell death. Thereafter, we
      screened a series of novel slow H2S donors for similar activity. One such
      compound, FW1256, concentration dependently decreased TNFalpha, IL-6, PGE2 and NO
      generation in LPS-stimulated RAW264.7 macrophages and BMDMs. FW1256 also
      significantly reduced IL-1beta, COX-2 and iNOS mRNA and protein in LPS-stimulated
      RAW264.7 macrophages. Mechanistically, FW1256 decreased NFkappaB activation as
      evidenced by reduced cytosolic phospho-IkappaBalpha levels and reduced nuclear
      p65 levels in LPS-stimulated RAW264.7 macrophages treated with FW1256. Using a
      H2S fluorescent probe in FW1256-treated RAW264.7 macrophages, H2S release from
      FW1256 was apparent over a period of 24h in these cells. Moreover, the effect of
      FW1256 on TNFalpha and IL-6 by FW1256 in LPS-stimulated RAW264.7 macrophages was
      reversed by treatment with the H2S scavenger, vitamin B12a. FW1256 had no
      cytotoxic effect on LPS-stimulated RAW264.7 macrophages or BMDMs. In vivo, FW1256
      administration also reduced IL-1beta, TNFalpha, nitrate/nitrite and PGE2 levels
      in LPS-treated mice. We show here a novel slow H2S-releasing compound that exerts
      anti-inflammatory effects in macrophages and in vivo. FW1256 may be a useful tool
      to study the biological effects of exogenous H2S and could also have future
      therapeutic value in inflammatory conditions.

PMID- 27687955
TI  - The thiirane-based selective MT1-MMP/MMP2 inhibitor ND-322 reduces melanoma tumor
      growth and delays metastatic dissemination.
AB  - MT1-MMP and MMP2 have been implicated as pro-tumorigenic and pro-metastatic
      factors in a wide variety of cancers including melanoma. We have previously
      demonstrated that MT1-MMP is highly expressed in melanoma where it promotes
      melanoma cell invasion and metastasis in part through the activation of its
      target MMP2. Given the accessibility of MMPs, as they are either secreted (e.g.
      MMP2) or membrane-tethered (e.g. MT1-MMP), they represent ideal targets for
      specific inhibition via small molecules. Here we show that the novel small
      molecule inhibitor ND-322 with high selectivity for MT1-MMP and MMP2, effectively
      inhibits MT1-MMP and MMP2 activity resulting in reduced in vitro melanoma cell
      growth, migration and invasion. Importantly, these inhibitory effects lead to
      significant reduction of melanoma tumor growth and metastasis. We further show
      that while cell migration and invasion could be similarly hampered by specific
      inhibition of either MT1-MMP or MMP2 via shRNAs, the growth inhibitory activity
      of ND-322 could only be mirrored by specific inhibition of MT1-MMP. These data
      support ND-322 as a novel effective inhibitor capable of counteracting both MT1
      MMP and MMP2, two key proteases involved in melanoma growth and metastasis. ND
      322 may therefore represent a new inhibitor in the repertoire of treatments
      against melanoma.

PMID- 27687957
TI  - Toll-like receptors and autophagy in interstitial lung diseases.
AB  - Interstitial lung diseases (ILDs) include a number of diseases whose pathogenesis
      still is not fully understood. Idiopathic pulmonary fibrosis (IPF), the most
      frequent and severe form of ILDs is an epithelial-driven disease and the
      treatment consists of the use of antifibrotic agents. In the rest of ILDs an
      inflammation-driven pathway is believed to be the main pathogenetic mechanism and
      treatment consists of the use of immunomodulatory agents. In both groups it is
      believed that infection can play an important role in the development and
      progression of the diseases. The immune system can recognize exogenous threats or
      endogenous stress through specialized receptors namely pattern recognition
      receptors (PRRs) which in turn, initiate downstream signaling pathways to control
      immune responses. Recently, a link between PRRs and autophagy, a specialized
      biological process involved in maintaining cellular homeostasis but also involved
      in various immunologic processes, has been described. In this review, we focus on
      the reciprocal influences of PRRs with particular emphasis on Toll-like receptors
      and autophagy in modulating innate immune responses.

PMID- 27687958
TI  - Treatment of diabetes: Crossing to the other side.
AB  - Type 2 diabetes mellitus affects nearly four hundred million people worldwide,
      and one of its major complications is cardiovascular disease. The evaluation of
      the effectiveness and safety of antidiabetic medication has been a challenging
      issue. Large clinical trials of new antidiabetic medications have used the non
      inferiority approach to ensure primary safety of the drug before its
      incorporation into clinical practice. Currently, the trend is to prove
      superiority, that is, to prove that the new drug has additional beneficial
      effects to those of standard medications. In this review, we present the results
      of recent clinical trials on type 2 diabetes mellitus medications and outline
      what can be anticipated from ongoing clinical trials.

PMID- 27687959
TI  - Effect of Irradiation on Queen Survivorship and Reproduction in the Invasive Fire
      Ant Solenopsis invicta (Hymenoptera: Formicidae) and a Proposed Phytosanitary
      Irradiation Treatment for Ants.
AB  - We studied radiation tolerance in queens of the red imported fire ant Solenopsis
      invicta Buren (Hymenoptera: Formicidae) to identify a dose that prevents
      reproduction. Virgin or fertile queens were collected from Santa Fe and Formosa
      provinces in Argentina and reared in the laboratory in microcolonies. Virgin
      queens were irradiated at 0 (control), 70, 90, 120, or 150 Gy, and fertile queens
      were irradiated at 0, 60, 125, and 190 Gy, and then followed for 11 wk in the
      microcolonies to evaluate survival and reproduction. Virgin queens lay trophic
      eggs that do not hatch, whereas fertile queens lay eggs that hatch and develop
      into brood. In general, queen oviposition and survival decreased with increasing
      irradiation dose. For virgin queens, no eggs were laid by irradiated queens after
      the third week, whereas the control queens continued laying eggs throughout the
      11-wk experiment. For fertile queens, only one larva and no pupae was observed in
      the 60 Gy treatment and no larvae or pupae were observed in the 125 and 190 Gy
      treatments, whereas a total of 431 larvae and 83 pupae were produced by untreated
      control queens during 11 wks. Survivorship of virgin and fertile queens was
      similarly reduced by irradiation treatment. These results with S. invicta are
      consistent with previous findings for three other invasive ants, Wasmannia
      auropunctata (Roger), Pheidole megacephala (F.), and Linephithema humile (Mayr),
      that are hitchhiker pests on fresh horticultural commodities. A radiation dose of
      150 Gy is proposed as a phytosanitary treatment to prevent reproduction in ants.

PMID- 27687960
TI  - Educating patients in IBD.

PMID- 27687961
TI  - Assessment of vitreous haze using ultra-wide field retinal imaging.
AB  - BACKGROUND: Conventional fundus imaging has been used to assess vitreous haze
      (VH) in patients with uveitis. Ultra-wide field (UWF) retinal imaging that uses
      scanning laser technology has not been evaluated for the detection of VH. This
      pilot study evaluates the ability of UWF imaging in detecting VH. Patients with
      intermediate, posterior, or panuveitis were examined to assess the level of VH
      using slit-lamp biomicroscopy. Colored fundus images were acquired using a Carl
      Zeiss FF450 camera. The same photographer obtained fundus images of the same eyes
      during the same visit by Optos UWF P200Tx retinal camera. Two graders
      independently analyzed UWF fundus images for presence or absence of VH, without
      quantifying the degree of VH using any scale. The images were analyzed using the
      composite red plus red-free wavelengths utilized by the Optos UWF camera and by
      using each wavelength exclusively. These findings were compared to clinical
      detection of VH and detection of VH using conventional fundus photography.
      RESULTS: Ninety-two eyes were included in the study. For composite UWF images,
      sensitivity was 0.27, specificity was 0.88, PPV was 0.31, NPV was 0.86, positive
      LR was 2.25, and negative LR was 0.83. For the conventional Zeiss images,
      sensitivity was 0.5, specificity was 0.84, PPV was 0.33, NPV was 0.91, positive
      LR was 3.13, and negative LR was 0.6. Agreement between the composite UWF and
      Zeiss techniques was substantial with k = 0.64. Inter-observer agreement for
      composite UWF images was also substantial with k = 0.65. Inter-observer agreement
      for Zeiss images was moderate with k = 0.471. Intra-observer agreement for both
      imaging modalities was substantial with a composite UWF k = 0.76 and Zeiss k =
      0.7. CONCLUSIONS: UWF fundus imaging using scanning laser technique may be used
      to assess VH and employed in the management of intermediate, posterior, and
      panuveitis.

PMID- 27687962
TI  - The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for
      Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the
      TNM Classification for Mesothelioma.
AB  - INTRODUCTION: The M component and TNM stage groupings for malignant pleural
      mesothelioma (MPM) have been empirical. The International Association for the
      Study of Lung Cancer developed a multinational database to propose evidence-based
      revisions for the eighth edition of the TNM classification of MPM. METHODS: Data
      from 29 centers were submitted either electronically or by transfer of existing
      institutional databases. The M component as it currently stands was validated by
      confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to
      overall survival (OS) between the clinical M0 (cM0) and cM1 categories. Candidate
      stage groups were developed by using a recursive partitioning and amalgamation
      algorithm applied to all cM0 cases. RESULTS: Of 3519 submitted cases, 2414 were
      analyzable and 84 were cM1 cases. Median OS for cM1 cases was 9.7 months versus
      13.4 months (p = 0.0013) for the locally advanced (T4 or N3) cM0 cases,
      supporting inclusion of only cM1 in the stage IV group. Exploratory analyses
      suggest a possible difference in OS for single- versus multiple-site cM1 cases. A
      recursive partitioning and amalgamation-generated survival tree on the OS
      outcomes restricted to cM0 cases with the newly proposed (eighth edition) T and N
      components indicates that optimal stage groupings for the eighth edition will be
      as follows: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA
      (T3N1), stage IIIB (T1-3N2 or any T4), and stage IV (any M1). CONCLUSIONS: This
      first evidence-based revision of the TNM classification for MPM leads to
      substantial changes in the T and N components and the stage groupings.

PMID- 27687966
TI  - Shear Modulus of the Partially Obstructed Rat Small Intestine.
AB  - A number of factors influence gastrointestinal tissue structure and mechanical
      properties such as the physical environment and diseases like partial
      obstruction. Hence multi-axial biomechanical properties are important for
      understanding the pathophysiology of the obstructed intestine. The aim was to
      estimate the multi-axial biomechanical properties, in particular with focus on
      the shear modulus. Partial obstruction of mid-jejunum was created surgically by
      placement of a polyethylene ring for two weeks in seven male rats. Sham operation
      was made in five other rats. At the time for termination, three 6-cm intestinal
      segments were used for histological and mechanical analysis. The segments were
      obtained distal (S1), proximal (S2) and further proximal (S3) to the site of
      obstruction or suturing site. The tri-axial testing included simultaneous
      torsion, inflation and longitudinal stretching. The lumen size, wall thickness,
      wall cross-sectional area, and muscle layer thickness increased in S2 and S3 of
      the obstructed rats (p < 0.001) with the most pronounced changes in S2. The
      opening angle decreased in S2 in the obstructed group (p < 0.05). The tissue
      stiffness increased in circumferential and longitudinal direction where as it was
      softer in shear direction, especially in S2 (p < 0.01). In conclusion, the
      histomorphological and mechanical properties including shear properties remodeled
      proximal to the intestinal obstruction site.

PMID- 27687963
TI  - The IASLC Mesothelioma Staging Project: Proposals for Revisions of the T
      Descriptors in the Forthcoming Eighth Edition of the TNM Classification for
      Pleural Mesothelioma.
AB  - INTRODUCTION: The current T component for malignant pleural mesothelioma (MPM)
      has been predominantly informed by surgical data sets and consensus. The
      International Association for the Study of Lung Cancer undertook revision of the
      seventh edition of the staging system for MPM with the goal of developing
      recommendations for the eighth edition. METHODS: Data elements including detailed
      T descriptors were developed by consensus. Tumor thickness at three pleural
      levels was also recorded. An electronic data capture system was established to
      facilitate data submission. RESULTS: A total of 3519 cases were submitted to the
      database. Of those eligible for T-component analysis, 509 cases had only clinical
      staging, 836 cases had only surgical staging, and 642 cases had both available.
      Survival was examined for T categories according to the current seventh edition
      staging system. There was clear separation between all clinically staged
      categories except T1a versus T1b (hazard ratio = 0.99, p = 0.95) and T3 versus T4
      (hazard ratio = 1.22, p = 0.09), although the numbers of T4 cases were small.
      Pathological staging failed to demonstrate a survival difference between adjacent
      categories with the exception of T3 versus T4. Performance improved with collapse
      of T1a and T1b into a single T1 category; no current descriptors were shifted or
      eliminated. Tumor thickness and nodular or rindlike morphology were significantly
      associated with survival. CONCLUSIONS: A recommendation to collapse both clinical
      and pathological T1a and T1b into a T1 classification will be made for the eighth
      edition staging system. Simple measurement of pleural thickness has prognostic
      significance and should be examined further with a view to incorporation into
      future staging.

PMID- 27687965
TI  - Web-Based Intervention to Reduce Substance Abuse and Depressive Symptoms in
      Mexico: Development and Usability Test.
AB  - BACKGROUND: The development of Web-based interventions for substance abuse in
      Latin America is a new field of interest with great potential for expansion to
      other Spanish-speaking countries. OBJECTIVE: This paper describes a project aimed
      to develop and evaluate the usability of the Web-based Help Program for Drug
      Abuse and Depression (Programa de Ayuda para Abuso de Drogas y Depresion, PAADD,
      in Spanish) and also to construct a systematic frame of reference for the
      development of future Web-based programs. METHODS: The PAADD aims to reduce
      substance use and depressive symptoms with cognitive behavioral techniques
      translated into Web applications, aided by the participation of a counselor to
      provide support and guidance. This Web-based intervention includes 4 steps: (1)
      My Starting Point, (2) Where Do I Want to Be? (3) Strategies for Change, and (4)
      Maintaining Change. The development of the program was an interactive multistage
      process. The first stage defined the core structure and contents, which were
      validated in stage 2 by a group of 8 experts in addiction treatment. Programming
      of the applications took place in stage 3, taking into account 3 types of end
      users: administrators, counselors, and substance users. Stage 4 consisted of
      functionality testing. In stage 5, a total of 9 health professionals and 20 drug
      users currently in treatment voluntarily interacted with the program in a
      usability test, providing feedback about adjustments needed to improve users'
      experience. RESULTS: The main finding of stage 2 was the consensus of the health
      professionals about the cognitive behavioral strategies and techniques included
      in PAADD being appropriate for changing substance use behaviors. In stage 5, the
      health professionals found the functionalities easy to learn; their suggestions
      were related to the page layout, inclusion of confirmation messages at the end of
      activities, avoiding "read more" links, and providing feedback about every
      activity. On the other hand, the users said the information presented within the
      modules was easy to follow and suggested more dynamic features with concrete
      instructions and feedback. CONCLUSIONS: The resulting Web-based program may have
      advantages over traditional face-to-face therapies owing to its low cost, wide
      accessibility, anonymity, and independence of time and distance factors. The
      detailed description of the process of designing a Web-based program is an
      important contribution to others interested in this field. The potential benefits
      must be verified in specific studies. TRIAL REGISTRATION: International Standard
      Randomized Controlled Trial Number (ISRCTN): 25429892; http://www.controlled
      trials.com/ISRCTN25429892 (Archived by WebCite at
      http://www.webcitation.org/6ko1Fsvym).

PMID- 27687964
TI  - The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N
      Descriptors in the Forthcoming Eighth Edition of the TNM Classification for
      Pleural Mesothelioma.
AB  - INTRODUCTION: Nodal categories for malignant pleural mesothelioma are derived
      from the lung cancer staging system and have not been adequately validated. The
      International Association for the Study of Lung Cancer developed a multinational
      database to generate evidence-based recommendations to inform the eighth edition
      of the TNM classification of malignant pleural mesothelioma. METHODS: Data from
      29 centers were entered prospectively (n = 1566) or by transfer of retrospective
      data (n = 1953). Survival according to the seventh edition N categories was
      evaluated using Kaplan-Meier survival curves and Cox proportional hazards
      regression analysis. Survival was measured from the date of diagnosis. RESULTS:
      There were 2432 analyzable cases: 1603 had clinical (c) staging, 1614 had
      pathologic (p) staging, and 785 had both. For clinically staged tumors there was
      no separation in Kaplan-Meier curves between cN0, cN1 or cN2 (cN1 versus cN0
      hazard ratio [HR] = 1.06, p = 0.77 and cN2 versus cN1 HR = 1.04, p = 0.85). For
      pathologically staged tumors, patients with pN1 or pN2 tumors had worse survival
      than those with pN0 tumors (HR = 1.51, p < 0.0001) but no survival difference was
      noted between those with pN1 and pN2 tumors (HR = 0.99, p = 0.99). Patients with
      both pN1 and pN2 nodal involvement had poorer survival than those with pN2 tumors
      only (HR = 1.60, p = 0.007) or pN0 tumors (HR = 1.62, p < 0.0001). CONCLUSIONS: A
      recommendation to collapse both clinical and pN1 and pN2 categories into a single
      N category comprising ipsilateral, intrathoracic nodal metastases (N1) will be
      made for the eighth edition staging system. Nodes previously categorized as N3
      will be reclassified as N2.

PMID- 27687967
TI  - Structure-based design of a new series of N-(piperidin-3-yl)pyrimidine-5
      carboxamides as renin inhibitors.
AB  - The action of the aspartyl protease renin is the rate-limiting initial step of
      the renin-angiotensin-aldosterone system. Therefore, renin is a particularly
      promising target for blood pressure as well as onset and progression of
      cardiovascular and renal diseases. New pyrimidine derivatives 5-14 were designed
      in an attempt to enhance the renin inhibitory activity of compound 3 identified
      by our previous fragment-based drug design approach. Introduction of a basic
      amine essential for interaction with the two aspartic acids in the catalytic site
      and optimization of the S1/S3 binding elements including an induced-fit
      structural change of Leu114 ('Leu-in' to 'Leu-out') by a rational structure-based
      drug design approach led to the discovery of N-(piperidin-3-yl)pyrimidine-5
      carboxamide 14, a 65,000-fold more potent renin inhibitor than compound 3.
      Surprisingly, this remarkable enhancement in the inhibitory activity of compound
      14 has been achieved by the overall addition of only seven heavy atoms to
      compound 3. Compound 14 demonstrated excellent selectivity over other aspartyl
      proteases and moderate oral bioavailability in rats.

PMID- 27687968
TI  - A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole
      thiochroman hybrids and evaluation of their antimycobacterial, anticancer and
      AchE inhibitory activities.
AB  - A facile stereoselective synthesis of novel dispiro indeno
      pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar
      cycloaddition of azomethine ylides, generated in situ from ninhydrin and
      sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The
      synthesised compounds were screened for their antimycobacterial, anticancer and
      AchE inhibition activities. Compound 4l (IC50 1.07MUM) has been found to exhibit
      the most potent antimycobacterial activity compared to cycloserine (12 times),
      pyrimethamine (37 times) and ethambutol (IC50 <1.56MUM) and 6l (IC50=2.87MUM) is
      more active than both cycloserine (4 times) and pyrimethamine (12 times). Three
      compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell
      lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50
      values of 1.10 and 1.16MUmol/L respectively.

PMID- 27687969
TI  - Design, synthesis and biological evaluation of potential antibacterial
      butyrolactones.
AB  - Novel butyrolactone analogues were designed and synthesized based on the known
      lichen antibacterial compounds, lichesterinic acids (B-10 and B-11), by
      substituting different functional groups on the butyrolactone ring trying to
      enhance its activity. All synthesized butyrolactone analogues were evaluated for
      their in vitro antibacterial activity against Streptococcus gordonii. Among the
      derivatives, B-12 and B-13 had the lowest MIC of 9.38MUg/mL where they have shown
      to be stronger bactericidals, by 2-3 times, than the reference antibiotic,
      doxycycline. These two compounds were then checked for their cytotoxicity against
      human gingival epithelial cell lines, Ca9-22, and macrophages, THP-1, by MTT and
      LDH assays which confirmed their safety against the tested cell lines. A
      preliminary study of the structure-activity relationships unveiled that the
      functional groups at the C4 position had an important influence on the
      antibacterial activity. An optimum length of the alkyl chain at the C5 position
      registered the best antibacterial inhibitory activity however as its length
      increased the bactericidal effect increased as well. This efficiency was attained
      by a carboxyl group substitution at the C4 position indicating the important dual
      role contributed by these two substituents which might be involved in their
      mechanism of action.

PMID- 27687970
TI  - Design, synthesis and evaluation of anti-CD123 antibody drug conjugates.
AB  - Leukemia stem cells (LSCs) account for the development of drug resistance and
      increased recurrence rate in acute myeloid leukemia (AML) patients. Targeted drug
      delivery to leukemia stem cells remains a major challenge in AML chemotherapy.
      Overexpressed interleukin-3 receptor alpha chain, CD123, on the surface of
      leukemia stem cells was reported to be a potential target in AML treatment. Here,
      we designed and developed an antibody drug conjugate (CD123-CPT) by integrating
      anti-CD123 antibody with a chemotherapeutic agent, Camptothecin (CPT), via a
      disulfide linker. The linker is biodegradable in the presence of Glutathione
      (GSH, an endogenous component in cells), which leads to release of CPT. Anti
      CD123 antibody conjugates showed significant higher cellular uptake in CD123
      overexpressed tumor cells. More importantly, CD123-CPT demonstrated potent
      inhibitory effects on CD123-overexpressed tumor cells. Consequently, these
      results provide a promising targeted chemotherapeutical strategy for AML
      treatment.

PMID- 27687971
TI  - Tyrosyl-DNA phosphodiesterase inhibitors: Progress and potential.
AB  - DNA topoisomerases are essential during transcription and replication. The
      therapeutic mechanism of action of topoisomerase inhibitors is enzyme poisoning
      rather than catalytic inhibition. Tyrosyl-DNA phosphodiesterases 1 or 2 were
      found as DNA repair enzymes hydrolyzing the covalent bond between the tyrosyl
      residue of topoisomerases I or II and the 3'- or 5'-phosphate groups in DNA,
      respectively. Tyrosyl-DNA phosphodiesterase 1 is a key enzyme in DNA repair
      machinery and a promising target for antitumor and neurodegenerative therapy.
      Inhibitors of tyrosyl-DNA phosphodiesterase 1 could act synergistically with
      topoisomerase I inhibitors and thereby potentiate the effects of topoisomerase I
      poisons. Tyrosyl-DNA phosphodiesterase 2 is an enzyme that specifically repairs
      DNA damages induced by topoisomerase II poisons and causes resistance to these
      drugs. Selective inhibition of tyrosyl-DNA phosphodiesterase 2 may be a novel
      approach to overcome intrinsic or acquired resistance to topoisomerase II
      targeted drug therapy. Thus, agents that inhibit tyrosyl-DNA phosphodiesterases 1
      and 2 have many applications in biochemical and physiological research and they
      have the potential to become anticancer and antiviral drugs. The structures,
      mechanism of action and therapeutic rationale of tyrosyl-DNA phosphodiesterase
      inhibitors and their development for combinations with topoisomerase inhibitors
      and DNA damaging agents are discussed.

PMID- 27687973
TI  - Measuring time utilization of pharmacists in the Birmingham Free Clinic
      dispensary.
AB  - BACKGROUND: Free and charitable clinics are a critical part of America's
      healthcare safety net. Although informatics tools have the potential to mitigate
      many of the organizational and service-related challenges facing these clinics,
      little research attention has been paid to the workflows and potential impact of
      electronic systems in these settings. In previous work, we performed a
      qualitative investigation at a free clinic dispensary to identify workflow
      challenges that may be alleviated through introduction of informatics
      interventions. However, this earlier study did not quantify the magnitude of
      these challenges. Time-motion studies offer a precise standard in quantifying
      healthcare workers' time expenditures on clinical activities, and can provide
      valuable insight into system specifications. These data, informed by a lean
      healthcare perspective, provide a quality improvement framework intended to
      maximize value and eliminate waste in inefficient workflow processes. METHODS: We
      performed a continuous observation time-motion study in the Birmingham Free
      Clinic dispensary. Two researchers followed pharmacists over the course of three
      general clinic sessions and recorded the duration of specific tasks. Pharmacists
      were then asked to identify tasks as value-added or non-value-added to facilitate
      calculation of the value quotient, a metric used to determine a workflow's level
      of efficiency. RESULTS: Four high-level workflow categories occupied almost 95 %
      of pharmacist time: prescription (Rx) preparation (39.8 %), clinician interaction
      (21.5 %), EMR operations (14.8 %), and patient interaction (18.7 %). Pharmacists
      invested the largest portion of time in prescription preparation, with 21.8 % of
      pharmacist time spent handwriting medication labels. Based on value
      categorizations made by the pharmacists, the average value quotient was found to
      be 40.3 %, indicating that pharmacists spend more than half of their time
      completing tasks they consider to be non-value-added. CONCLUSIONS: Our results
      show that pharmacists spend a large portion of their time preparing
      prescriptions, primarily the handwritten labeling of medication bottles and
      documentation tasks, which is not an optimal utilization of pharmacist expertise.
      The value quotient further supports that there are many wasteful tasks that may
      benefit from workflow redesign and health information technology, which could
      result in efficiency improvements for pharmacists.

PMID- 27687972
TI  - Deep brain stimulation of the posterior subthalamic area and the thalamus in
      patients with essential tremor: study protocol for a randomized controlled pilot
      trial.
AB  - BACKGROUND: Deep brain stimulation (DBS) of the ventral intermediate nucleus
      (VIM) of the thalamus is effective in medication refractory essential tremor
      (ET). In recent years, evidence has accumulated that the region ventral to the
      VIM, the posterior subthalamic area (PSA), might be an equally or even more
      effective target for electrode implantation. However, this evidence is primarily
      based on case series, cross-sectional observations, and retrospective data.
      METHODS/DESIGN: A prospective crossover pilot study investigating the effects of
      PSA stimulation in medication refractory ET patients was designed. In this study,
      bilateral electrodes are implanted such that at least one of the electrode
      contacts is located in the PSA and VIM, respectively. This implantation approach
      allows (1) a prospective double-blind investigation of the effects of PSA
      stimulation compared to baseline, as well as (2) a crossover comparison between
      VIM and PSA stimulation with respect to tremor suppression and side effect
      profiles. DISCUSSION: The results of this double-blinded, prospective study will
      allow a better understanding of the effects and side effects of PSA compared to
      VIM-DBS in patients with ET. TRIAL REGISTRATION: German Clinical Trials Register:
      DRKS00004235 . Registered on 4 July 2012.

PMID- 27687974
TI  - SAR11 Bacteria: The Most Abundant Plankton in the Oceans.
AB  - SAR11 is a group of small, carbon-oxidizing bacteria that reach a global
      estimated population size of 2.4*1028 cells-approximately 25% of all plankton.
      They are found throughout the oceans but reach their largest numbers in
      stratified, oligotrophic gyres, which are an expanding habitat in the warming
      oceans. SAR11 likely had a Precambrian origin and, over geological time, evolved
      into the niche of harvesting labile, low-molecular-weight dissolved organic
      matter (DOM). SAR11 cells are minimal in size and complexity, a phenomenon known
      as streamlining that is thought to benefit them by lowering the material costs of
      replication and maximizing transport functions that are essential to competition
      at ultralow nutrient concentrations. One of the surprises in SAR11 metabolism is
      their ability to both oxidize and produce a variety of volatile organic compounds
      that can diffuse into the atmosphere. SAR11 cells divide slowly and lack many
      forms of regulation commonly used by bacterial cells to adjust to changing
      environmental conditions. As a result of genome reduction, they require an
      unusual range of nutrients, which leads to complex biochemical interactions with
      other plankton. The study of SAR11 is providing insight into the biogeochemistry
      of labile DOM and is affecting microbiology beyond marine science by providing a
      model for understanding the evolution and function of streamlined cells.

PMID- 27687976
TI  - Kinetic ways of tailoring phases in high entropy alloys.
AB  - The comprehensive performance of high entropy alloys (HEAs) depends on the phase
      selection significantly. However, up to now, investigations of the phase
      selection in HEAs mainly focused on the thermodynamic equilibrium phase, while
      kinetic ways of tailoring the phases in HEAs are seldom considered. In HEAs, the
      kinetics of sluggish diffusion and the numerous possible phases make the kinetics
      of phase transformation more complex and intriguing. Here, the kinetic effect in
      CoCrFeNiTi0.4 HEAs was investigated to reveal the possibility of controlling
      phase selection via kinetic ways for HEAs. The sigma, gamma' and R phases in the
      CoCrFeNiTi0.4 HEA can be controlled under different cooling rate both in
      solidification and solid transformation. The theoretical analyses revealed the
      kinetic effect on phase selection. The method proposed here, tailoring the phases
      with different kinetic ways, could be used to prepare promising HEAs with very
      rich composition design.

PMID- 27687975
TI  - Novel roles for the radial spoke head protein 9 in neural and neurosensory cilia.
AB  - Cilia are cell surface organelles with key roles in a range of cellular
      processes, including generation of fluid flow by motile cilia. The axonemes of
      motile cilia and immotile kinocilia contain 9 peripheral microtubule doublets, a
      central microtubule pair, and 9 connecting radial spokes. Aberrant radial spoke
      components RSPH1, 3, 4a and 9 have been linked with primary ciliary dyskinesia
      (PCD), a disorder characterized by ciliary dysmotility; yet, radial spoke
      functions remain unclear. Here we show that zebrafish Rsph9 is expressed in cells
      bearing motile cilia and kinocilia, and localizes to both 9 + 2 and 9 + 0 ciliary
      axonemes. Using CRISPR mutagenesis, we show that rsph9 is required for motility
      of presumptive 9 + 2 olfactory cilia and, unexpectedly, 9 + 0 neural cilia. rsph9
      is also required for the structural integrity of 9 + 2 and 9 + 0 ciliary
      axonemes. rsph9 mutant larvae exhibit reduced initiation of the acoustic startle
      response consistent with hearing impairment, suggesting a novel role for Rsph9 in
      the kinocilia of the inner ear and/or lateral line neuromasts. These data
      identify novel roles for Rsph9 in 9 + 0 motile cilia and in sensory kinocilia,
      and establish a useful zebrafish PCD model.

PMID- 27687977
TI  - Dysbiosis of small intestinal microbiota in liver cirrhosis and its association
      with etiology.
AB  - Cirrhosis-associated duodenal dysbiosis is not yet clearly defined. In this
      research, duodenal mucosal microbiota was analyzed in 30 cirrhotic patients and
      28 healthy controls using 16S rRNA gene pyrosequencing methods. The principal
      coordinate analysis revealed that cirrhotic patients were colonized by remarkable
      different duodenal mucosal microbiota in comparison with controls. At the genus
      level, Veillonella, Megasphaera, Dialister, Atopobium, and Prevotella were found
      overrepresented in cirrhotic duodenum. And the duodenal microbiota of healthy
      controls was enriched with Neisseria, Haemophilus, and SR1 genera incertae sedis.
      On the other hand, based on predicted metagenomes analyzed, gene pathways related
      to nutrient absorption (e.g. sugar and amino acid metabolism) were highly
      abundant in cirrhosis duodenal microbiota, and functional modules involved in
      bacterial proliferation and colonization (e.g. bacterial motility proteins and
      secretion system) were overrepresented in controls. When considering the etiology
      of cirrhosis, two operational taxonomic units (OTUs), OTU-23 (Neisseria) and OTU
      36 (Gemella), were found discriminative between hepatitis-B-virus related
      cirrhosis and primary biliary cirrhosis. The results suggest that the structure
      of duodenal mucosa microbiota in cirrhotic patients is dramatically different
      from healthy controls. The duodenum dysbiosis might be related to alterations of
      oral microbiota and changes in duodenal micro-environment.

PMID- 27687978
TI  - Radon versus other lung cancer risk factors: How accurate are the attribution
      estimates?
AB  - : This notebook paper provides a brief overview of attribution estimates for some
      key lung cancer risk factors, focusing on indoor radon gas exposure in the U.S.,
      UK, and Canada. Tobacco smoking represents the primary cause of lung cancer
      worldwide. Radon is regarded as the second leading lung cancer risk factor in the
      U.S. and Canada. It can be observed, however, that the reported estimates appear
      not to add up to the maximum cumulative attribution of 100%. IMPLICATIONS:
      Limitations and uncertainties associated with published epidemiological studies
      and the observed lack of consistency in lung cancer attribution estimates for
      radon and other non-smoking lung cancer risk factors should be taken into
      consideration by policy makers in setting population health protection
      priorities.

PMID- 27687980
TI  - Tumour metabolism: Reflecting their origins.

PMID- 27687981
TI  - Tumour metabolism: Translating the undruggable target.

PMID- 27687979
TI  - Mouse models in oncoimmunology.
AB  - Fundamental cancer research and the development of efficacious antineoplastic
      treatments both rely on experimental systems in which the relationship between
      malignant cells and immune cells can be studied. Mouse models of transplantable,
      carcinogen-induced or genetically engineered malignancies - each with their
      specific advantages and difficulties - have laid the foundations of
      oncoimmunology. These models have guided the immunosurveillance theory that
      postulates that evasion from immune control is an essential feature of cancer,
      the concept that the long-term effects of conventional cancer treatments mostly
      rely on the reinstatement of anticancer immune responses and the preclinical
      development of immunotherapies, including currently approved immune checkpoint
      blockers. Specific aspects of pharmacological development, as well as attempts to
      personalize cancer treatments using patient-derived xenografts, require the
      development of mouse models in which murine genes and cells are replaced with
      their human equivalents. Such 'humanized' mouse models are being progressively
      refined to characterize the leukocyte subpopulations that belong to the innate
      and acquired arms of the immune system as they infiltrate human cancers that are
      subjected to experimental therapies. We surmise that the ever-advancing
      refinement of murine preclinical models will accelerate the pace of therapeutic
      optimization in patients.

PMID- 27687983
TI  - Wnt/beta-catenin signaling pathway activation is required for proliferation of
      chicken primordial germ cells in vitro.
AB  - Here, we investigated the role of the Wnt/beta-catenin signaling pathway in
      chicken primordial germ cells (PGCs) in vitro. We confirmed the expression of Wnt
      signaling pathway-related genes and the localization of beta-catenin in the
      nucleus, revealing that this pathway is potentially activated in chicken PGCs.
      Then, using the single-cell pick-up assay, we examined the proliferative capacity
      of cultured PGCs in response to Wnt ligands, a beta-catenin-mediated Wnt
      signaling activator (6-bromoindirubin-3'-oxime [BIO]) or inhibitor (JW74), in the
      presence or absence of basic fibroblast growth factor (bFGF). WNT1, WNT3A, and
      BIO promoted the proliferation of chicken PGCs similarly to bFGF, whereas JW74
      inhibited this proliferation. Meanwhile, such treatments in combination with bFGF
      did not show a synergistic effect. bFGF treatment could not rescue PGC
      proliferation in the presence of JW74. In addition, we confirmed the
      translocation of beta-catenin into the nucleus by the addition of bFGF after JW74
      treatment. These results indicate that there is signaling crosstalk between FGF
      and Wnt, and that beta-catenin acts on PGC proliferation downstream of bFGF. In
      conclusion, our study suggests that Wnt signaling enhances the proliferation of
      chicken PGCs via the stabilization of beta-catenin and activation of its
      downstream genes.

PMID- 27687985
TI  - A Critique of Henrik Friberg-Fernros's Defense of the Substance View.
AB  - Proponents of the substance view contend that abortion is seriously morally wrong
      because it is killing something with the same inherent value and right to life as
      you or I. Rob Lovering offers two innovative criticisms of the anti-abortion
      position taken by the substance view - the rescue argument and the problem of
      spontaneous abortion. Henrik Friberg-Fernros offers an interesting response to
      Lovering, but one I argue would be inconsistent with the anti-abortion stance
      taken by most substance view theorists.

PMID- 27687984
TI  - MITK-OpenIGTLink for combining open-source toolkits in real-time computer
      assisted interventions.
AB  - PURPOSE: Due to rapid developments in the research areas of medical imaging,
      medical image processing and robotics, computer-assisted interventions (CAI) are
      becoming an integral part of modern patient care. From a software engineering
      point of view, these systems are highly complex and research can benefit greatly
      from reusing software components. This is supported by a number of open-source
      toolkits for medical imaging and CAI such as the medical imaging interaction
      toolkit (MITK), the public software library for ultrasound imaging research
      (PLUS) and 3D Slicer. An independent inter-toolkit communication such as the open
      image-guided therapy link (OpenIGTLink) can be used to combine the advantages of
      these toolkits and enable an easier realization of a clinical CAI workflow.
      METHODS: MITK-OpenIGTLink is presented as a network interface within MITK that
      allows easy to use, asynchronous two-way messaging between MITK and clinical
      devices or other toolkits. Performance and interoperability tests with MITK
      OpenIGTLink were carried out considering the whole CAI workflow from data
      acquisition over processing to visualization. RESULTS: We present how MITK
      OpenIGTLink can be applied in different usage scenarios. In performance tests,
      tracking data were transmitted with a frame rate of up to 1000 Hz and a latency
      of 2.81 ms. Transmission of images with typical ultrasound (US) and greyscale
      high-definition (HD) resolutions of [Formula: see text] and [Formula: see text]
      is possible at up to 512 and 128 Hz, respectively. CONCLUSION: With the
      integration of OpenIGTLink into MITK, this protocol is now supported by all
      established open-source toolkits in the field. This eases interoperability
      between MITK and toolkits such as PLUS or 3D Slicer and facilitates cross-toolkit
      research collaborations. MITK and its submodule MITK-OpenIGTLink are provided
      open source under a BSD-style licence ( http://mitk.org ).

PMID- 27687986
TI  - The Google matrix controls the stability of structured ecological and biological
      networks.
AB  - May's celebrated theoretical work of the 70's contradicted the established
      paradigm by demonstrating that complexity leads to instability in biological
      systems. Here May's random-matrix modelling approach is generalized to realistic
      large-scale webs of species interactions, be they structured by networks of
      competition, mutualism or both. Simple relationships are found to govern these
      otherwise intractable models, and control the parameter ranges for which
      biological systems are stable and feasible. Our analysis of model and real
      empirical networks is only achievable on introducing a simplifying Google-matrix
      reduction scheme, which in the process, yields a practical ecological eigenvalue
      stability index. These results provide an insight into how network topology,
      especially connectance, influences species stable coexistence. Constraints
      controlling feasibility (positive equilibrium populations) in these systems are
      found more restrictive than those controlling stability, helping explain the
      enigma of why many classes of feasible ecological models are nearly always
      stable.

PMID- 27687982
TI  - Epstein-Barr virus: more than 50 years old and still providing surprises.
AB  - It is more than 50 years since the Epstein-Barr virus (EBV), the first human
      tumour virus, was discovered. EBV has subsequently been found to be associated
      with a diverse range of tumours of both lymphoid and epithelial origin. Progress
      in the molecular analysis of EBV has revealed fundamental mechanisms of more
      general relevance to the oncogenic process. This Timeline article highlights key
      milestones in the 50-year history of EBV and discusses how this virus provides a
      paradigm for exploiting insights at the molecular level in the diagnosis,
      treatment and prevention of cancer.

PMID- 27687987
TI  - Discontinuation of long-term adalimumab treatment in patients with juvenile
      idiopathic arthritis-associated uveitis.
AB  - PURPOSE: The purpose of this study was to evaluate the discontinuation of
      adalimumab (ADA) treatment in patients with juvenile idiopathic arthritis
      associated uveitis (JIAU). METHODS: Patients in whom ADA treatment was initiated
      for JIAU were included in this retrospective analysis. Reasons for discontinuing
      ADA treatment in patients with primary treatment response were analysed. RESULTS:
      Within a group of 387 JIAU patients, 59 of 68 patients who were treated with ADA
      achieved a sufficient response to treatment within 6 months. Here, 39 patients
      (66.1 %) were still on therapy at their last follow-up visit (mean treatment
      duration of 38.3 months, range 12-91). In another 20 patients, ADA had been
      discontinued after 1 or 2 years or later, in 10 % (n = 2), 45 % (n = 9) and 45 %
      (n = 9) of patients, respectively (mean 30.6 months; range 10-65). Reasons for
      discontinuing ADA were reactivation of uveitis (n = 8, 3.93 per 100 patient
      years) or arthritis (n = 4; 1.97 per 100 patient-years), or >=2 years of complete
      disease inactivity (n = 3, 1.47 per 100 patient-years), adverse events (n = 4;
      1.89 per 100 patient-years), or other (n = 1; 0.47 per 100 patient-years).
      CONCLUSIONS: The data show a good primary response to ADA in patients with
      refractory JIAU. Due to the increasing rate of adalimumab failure or adverse
      events during long-term treatment, further treatment options may be required.

PMID- 27687989
TI  - Maternal Body Mass Index and Risk of Autism Spectrum Disorders in Offspring: A
      Meta-analysis.
AB  - Controversial results of the association between maternal body mass index (BMI)
      and risk of autism spectrum disorder (ASD) in offspring were reported among
      several studies. This meta-analysis was conducted to estimate the overall
      association between maternal BMI and risk of ASD in offspring. PubMed, EMBASE,
      Web of Science, and the Cochrane Library were searched until January 2016. Cohort
      and case-control studies addressing the association between maternal BMI and risk
      of ASD in offspring were included. We used random-effect models to estimate the
      summary relative risks (RRs), we also performed a dose-response meta-analysis to
      estimate the trend from the correlated log RR estimates across levels of BMI
      quantitatively. Totally, 6 cohort studies and 1 case-control study involving
      8,403 cases and 509,167 participants were included for analysis. The summary RR
      (95% confidence interval) for ASD in offspring in relation to maternal
      underweight, overweight, and obesity vs. normal weight during pre-pregnancy or
      pregnancy, was 1.07 (0.93, 1.23), 1.28 (1.19, 1.36) and 1.36 (1.03, 1.78),
      respectively. A linear dose-response relationship was found, with a pooled RR of
      1.16 (1.01, 1.33) for each 5 kg/m2. increment in maternal BMI. The present study
      suggests that excessive maternal BMI is associated with increased ASD risk in
      offspring.

PMID- 27687988
TI  - One-year outcome of combination therapy with intravitreal aflibercept and
      verteporfin photodynamic therapy for polypoidal choroidal vasculopathy.
AB  - PURPOSE: The purpose of the study was to evaluate the 1-year visual and
      anatomical outcomes of combination therapy with intravitreal aflibercept (IVA)
      and verteporfin photodynamic therapy (vPDT) for polypoidal choroidal vasculopathy
      (PCV), and to determine the predictors of a good visual outcome. METHODS: This
      was a prospective case-series study. Twenty eyes from 20 treatment-naive PCV
      patients were treated with combination therapy with IVA and vPDT. Best-corrected
      visual acuity (BCVA) and morphological parameters including polypoidal lesions in
      indocyanine green angiography (ICGA) were evaluated over 12 months of follow-up.
      RESULTS: The mean logMAR BCVA was significantly improved from 0.30 at baseline to
      0.20 at 3 months and 0.18 at 12 months. The mean central retinal thickness was
      also significantly improved at 3 months and at 12 months. In ICGA, complete
      regression of polypoidal lesions was found in 14 out of 20 eyes (70 %) at 3
      months and in 14 out of 18 eyes (78 %) at 12 months although no ICGA were done on
      two eyes. In the multivariate logistic regression analyses, the baseline greatest
      linear dimension was found as a significant predictive factor for good visual
      improvement (?0.3 LogMAR units improvement from baseline) at 12 months.
      CONCLUSION: In this study, combination therapy with IVA and vPDT gave visual and
      anatomical improvements to treatment-naive PCV patients over 12 months of follow
      up period.

PMID- 27687990
TI  - Reevaluating multicolor flow cytometry to assess microbial viability.
AB  - Flow cytometry is a rapid and quantitative method to determine bacterial
      viability. Although different stains can be used to establish viability, staining
      protocols are inconsistent and lack a general optimization approach. Very few
      "true" multicolor protocols, where dyes are combined in one sample, have been
      developed for microbiological applications. In this mini-review, the discrepancy
      between protocols for cell-permeant nucleic acid and functional stains are
      discussed as well as their use as viability dyes. Furthermore, optimization of
      staining protocols for a specific setup are described. Original data using the
      red-excitable SYTO dyes SYTO 59 to 64 and SYTO 17, combined with functional
      stains, for double and triple staining applications is also included. As each dye
      and dye combination behaves differently within a certain combination of medium
      matrix, microorganism, and instrument, protocols need to be tuned to obtain
      reproducible results. Therefore, single, double, and triple stains are reviewed,
      including the different parameters that influence staining such as stain
      kinetics, optimal stain concentration, and the effect of the chelator EDTA as
      membrane permeabilizer. In the last section, we highlight the need to investigate
      the stability of multicolor assays to ensure correct results as multiwell
      autoloaders are now commonly used.

PMID- 27687991
TI  - Transfer and consumption of oxygen during the cultivation of the ectomycorrhizal
      fungus Rhizopogon nigrescens in an airlift bioreactor.
AB  - The study had the objective of examining the aspects involved in the cultivation
      of ectomycorrhizal fungi for the production of commercially sustainable inoculant
      to attend the demands of the seedling nursery industry. It focused on certain
      parameters, such as the oxygen consumption levels, during the cultivation of the
      ectomycorrhizal fungus Rhizopogon nigrescens CBMAI 1472, which was performed in a
      5-L airlift bioreactor. The dynamic method was employed to determine the
      volumetric coefficient for the oxygen transfer (k L a) and the specific oxygen
      uptake rate (Q O2 ). The results indicate that specific growth rates (MU X ) and
      oxygen consumption decline rapidly with time, affected mainly by increases in
      biomass concentration (X). Increases in X are obtained primarily by increases in
      the size of pellets that are formed, altering, consequently, the cultivation
      dynamics. This is the result of natural increases in transferring resistance that
      are observed in these environments. Therefore, to avoid critical conditions that
      affect viability and the productivity of the process, particular settings are
      discussed.

PMID- 27687993
TI  - Effective production of fermentable sugars from brown macroalgae biomass.
AB  - Brown macroalgae are renewable and sustainable biomass resources for the
      production of biofuels and chemicals, owing to their high levels of carbohydrates
      and low levels of lignin. To increase the biological usage of brown macroalgae,
      it is necessary to depolymerize the polysaccharides that generate macroalgal
      monomeric sugars or sugar derivatives and to convert them into fermentable sugars
      for the production of biofuels and chemicals. In this review, we discuss the
      chemical and enzymatic saccharification of the major carbohydrates found in brown
      macroalgae and the use of the resulting constituents in the production of
      biofuels and chemicals, as well as high-value health-benefiting functional
      oligosaccharides and sugars. We also discuss recently reported experimental
      results, novel enzymes, and technological breakthroughs that are related to
      polysaccharide depolymerization, fermentable sugar production, and the biological
      conversion of non-favorable sugars for fermentation using industrial
      microorganisms. This review provides a comprehensive perspective of the efficient
      utilization of brown macroalgae as renewable resources for the production of
      biofuels and chemicals.

PMID- 27687992
TI  - Adhesion of the genome-sequenced Lactococcus lactis subsp. cremoris IBB477 strain
      is mediated by specific molecular determinants.
AB  - Understanding the nature of mucus-microbe interactions will provide important
      information that can help to elucidate the mechanisms underlying probiotic
      adhesion. This study focused on the adhesive properties of the Lactococcus lactis
      subsp. cremoris IBB477 strain, previously shown to persist in the
      gastrointestinal tract of germ-free rats. The shear flow-induced detachment of L.
      lactis cells was investigated under laminar flow conditions. Such a dynamic
      approach demonstrated increased adhesion to bare and mucin-coated polystyrene for
      IBB477, compared to that observed for the MG1820 control strain. To identify
      potential genetic determinants giving adhesive properties to IBB477, the improved
      high-quality draft genome sequence comprising chromosome and five plasmids was
      obtained and analysed. The number of putative adhesion proteins was determined on
      the basis of surface/extracellular localisation and/or the presence of adhesion
      domains. To identify proteins essential for the IBB477 specific adhesion
      property, nine deletion mutants in chromosomal genes have been constructed and
      analysed using adhesion tests on bare polystyrene as well as mucin-, fibronectin-
      or collagen IV-coated polystyrene plates in comparison to the wild-type strain.
      These experiments demonstrated that gene AJ89_07570 encoding a protein containing
      DUF285, MucBP and four Big_3 domains is involved in adhesion to bare and mucin
      coated polystyrene. To summarise, in the present work, we characterised the
      adhesion of IBB477 under laminar flow conditions; identified the putative
      adherence factors present in IBB477, which is the first L. lactis strain
      exhibiting adhesive and mucoadhesive properties to be sequenced and demonstrated
      that one of the proteins containing adhesion domains contributes to adhesion.

PMID- 27687994
TI  - Stereospecificity of Corynebacterium glutamicum 2,3-butanediol dehydrogenase and
      implications for the stereochemical purity of bioproduced 2,3-butanediol.
AB  - The stereochemistry of 2,3-butanediol (2,3-BD) synthesis in microbial
      fermentations is important for many applications. In this work, we showed that
      Corynebacterium glutamicum endowed with the Lactococcus lactis genes encoding
      alpha-acetolactate synthase and decarboxylase activities produced meso-2,3-BD as
      the major end product, meaning that (R)-acetoin is a substrate for endogenous 2,3
      butanediol dehydrogenase (BDH) activity. This is curious in view of the reported
      absolute stereospecificity of C. glutamicum BDH for (S)-acetoin (Takusagawa et
      al. Biosc Biotechnol Biochem 65:1876-1878, 2001). To resolve this discrepancy,
      the enzyme encoded by butA Cg was produced in Escherichia coli and purified, and
      the stereospecific properties of the pure protein were examined. Activity assays
      monitored online by 1H-NMR using racemic acetoin and an excess of NADH showed an
      initial, fast production of (2S,3S)-2,3-BD, followed by a slow (~20-fold lower
      apparent rate) formation of meso-2,3-BD. Kinetic parameters for (S)-acetoin, (R)
      acetoin, meso-2,3-BD and (2S,3S)-BD were determined by spectrophotometric assays.
      V max values for (S)-acetoin and (R)-acetoin were 119 +/- 15 and 5.23 +/- 0.06
      MUmol min-1 mg protein-1, and K m values were 0.23 +/- 0.02 and 1.49 +/- 0.07 mM,
      respectively. We conclude that C. glutamicum BDH is not absolutely specific for
      (S)-acetoin, though this is the preferred substrate. Importantly, the low
      activity of BDH with (R)-acetoin was sufficient to support high yields of meso
      2,3-BD in the engineered strain C. glutamicum DeltaaceEDeltapqoDeltaldhA(pEKEx2
      als,aldB,butA Cg ). Additionally, we found that the BDH activity was nearly
      abolished upon inactivation of butA Cg (from 0.30 +/- 0.03 to 0.004 +/- 0.001
      MUmol min-1 mg protein-1), indicating that C. glutamicum expresses a single BDH
      under the experimental conditions examined.

PMID- 27687995
TI  - Screening of novel bacteria for the 2,3-butanediol production.
AB  - Biotechnologically produced 2,3-butanediol (2,3-BDO) is a potential starting
      material for industrial bulk chemicals such as butadiene or methyl ethyl ketone
      which are currently produced from fossil feedstocks. So far, the highest 2,3-BDO
      concentrations have been obtained with risk group 2 microorganisms. In this
      study, three risk group 1 microorganisms are presented that are so far unknown
      for an efficient production of 2,3-BDO. The strains Bacillus atrophaeus NRS-213,
      Bacillus mojavensis B-14698, and Bacillus vallismortis B-14891 were evaluated
      regarding their ability to produce high 2,3-BDO concentrations with a broad range
      of different carbon sources. A maximum 2,3-BDO concentration of 60.4 g/L was
      reached with the strain B. vallismortis B-14891 with an initial glucose
      concentration of 200 g/L within 55 h in a batch cultivation. Besides glucose, B.
      vallismortis B-14891 converts 14 different substrates that can be obtained from
      residual biomass sources to 2,3-BDO. Therefore B. vallismortis B-14891 is a
      promising candidate for the large-scale production of 2,3-BDO with low-cost
      substrates.

PMID- 27687996
TI  - Assessment of active methanogenic archaea in a methanol-fed upflow anaerobic
      sludge blanket reactor.
AB  - Methanogenic archaea enrichment of a granular sludge was undertaken in an upflow
      anaerobic sludge blanket (UASB) reactor fed with methanol in order to enrich
      methylotrophic and hydrogenotrophic methanogenic populations. A microbial
      community assessment, in terms of microbial composition and activity-throughout
      the different stages of the feeding process with methanol and acetate-was
      performed using specific methanogenic activity (SMA) assays, quantitative real
      time polymerase chain reaction (qPCR), and high-throughput sequencing of 16S
      ribosomal RNA (rRNA) genes from DNA and complementary DNA (cDNA). Distinct
      methanogenic enrichment was revealed by qPCR of mcrA gene in the methanol-fed
      community, being two orders of magnitude higher with respect to the initial
      inoculum, achieving a final mcrA/16S rRNA ratio of 0.25. High-throughput
      sequencing analysis revealed that the resulting methanogenic population was
      mainly composed by methylotrophic archaea (Methanomethylovorans and Methanolobus
      genus), being also highly active according to the RNA-based assessment. SMA
      confirmed that the methylotrophic pathway, with a direct conversion of methanol
      to CH4, was the main step of methanol degradation in the UASB. The biomass from
      the UASB, enriched in methanogenic archaea, may bear great potential as
      additional inoculum for bioreactors to carry out biogas production and other
      related processes.

PMID- 27687997
TI  - Organogenesis and foetal haemodynamics during the normal gestation of healthy
      black-rumped agoutis (Dasyprocta prymnolopha, Wagler, 1831) bred in captivity.
AB  - The objective of this study was to define the patterns of organogenesis and
      foetal haemodynamics during the normal gestation of healthy agoutis (Dasyprocta
      prymnolopha) kept in captivity. Thirty pregnant agoutis that ranged in size from
      small to medium and weighed between 2.5 and 3 kg underwent B-mode and Doppler
      ultrasonography for the biometric evaluation of the foetal organs. The foetal
      aortic blood flow proved to be predominantly systolic, and the measured flow
      velocity was 78.89 +/- 2.95 cm/s, with a maximum pressure gradient of 2.12 +/-
      0.27 mmHg. The liver was characterized by its large volume, occupying the entire
      cranial aspect of the abdominal cavity, and it was associated cranially with the
      diaphragm and caudally with the stomach. The flow velocity in the portal vein was
      estimated to equal 12.17 +/- 2.37 cm/s, with a resistivity index of 0.82 +/-
      0.05. The gallbladder was centrally located and protruded cranially towards the
      diaphragm. The spleen was visualized as an elongated structure with tapered
      cranial and caudal extremities, and the foetal kidneys were visualized
      bilaterally in the retroperitoneal region, with the right kidney positioned
      slightly more cranially than the left. The morphological characterization and
      hemodynamic analysis of the foetal organs of black-rumped agoutis via B-mode and
      Doppler ultrasonography allow determination of the vascular network and of
      reference values for the blood flow required for perfusing the anatomical
      elements essential for maintaining the viability of foetuses at different
      gestational ages.

PMID- 27687999
TI  - A proteomic approach for the identification of immunotoxic properties of
      Tulipalin A.
AB  - The immune system is permanently exposed to several environmental influences that
      can have adverse effects on immune cells or organs leading to immunosuppression
      or inappropriate immunostimulation, called direct immunotoxicity. The natural
      compound Tulipalin A (TUPA), a lactone with alpha-methylene-gamma-butyrolactone
      moiety, can influence the immune system and lead to allergic contact dermatitis.
      This in vitro study focused on effects of TUPA using two immune cell lines
      (Jurkat T cells and THP-1 monocytes). To evaluate the immunotoxic potential of
      the compound, a proteomic approach applying 2D gel electrophoresis and MALDI
      TOF/TOF-MS in combination with metabolomic analysis was used after exposure of
      the cells to IC10 of TUPA. THP-1 cells showed a strong robustness to TUPA
      treatment since only five proteins were altered. In contrast, in Jurkat T cells
      an increase in the abundance of 66 proteins and a decrease of six proteins was
      determined. These intracellular proteins were mapped to biological processes.
      Especially an accumulation of chaperones and an influence on the purine synthesis
      were observed. The changes in purine synthesis were confirmed by metabolomic
      analysis. In conclusion, the data indicate possible target processes of low doses
      of TUPA in Jurkat T cells and provides knowledge of how TUPA affects the
      functionality of immune cells.

PMID- 27688000
TI  - Nonbacterial thrombotic endocarditis involving both the tricuspid and aortic
      valves.
AB  - A 71-year-old male presented after sudden onset of confusion and expressive
      aphasia. MRI head revealed multiple ischemic lesions consistent with cardio
      embolic pathophysiology. A computed tomography angiography of lung showed
      peripheral pulmonary emboli. He underwent a transesophageal echocardiogram as a
      part of the stroke workup and was found to have vegetations on both aortic and
      tricuspid valves. The blood cultures did not show any growth, and the patient
      remained afebrile during the course of hospitalization. A diagnosis of
      nonbacterial thrombotic embolism was made, and he was discharged on
      anticoagulation therapy with subcutaneous low molecular heparin.

PMID- 27687998
TI  - Volatile Organic Compounds Emitted by Fungal Associates of Conifer Bark Beetles
      and their Potential in Bark Beetle Control.
AB  - Conifer bark beetles attack and kill mature spruce and pine trees, especially
      during hot and dry conditions. These beetles are closely associated with
      ophiostomatoid fungi of the Ascomycetes, including the genera Ophiostoma,
      Grosmannia, and Endoconidiophora, which enhance beetle success by improving
      nutrition and modifying their substrate, but also have negative impacts on
      beetles by attracting predators and parasites. A survey of the literature and our
      own data revealed that ophiostomatoid fungi emit a variety of volatile organic
      compounds under laboratory conditions including fusel alcohols, terpenoids,
      aromatic compounds, and aliphatic alcohols. Many of these compounds already have
      been shown to elicit behavioral responses from bark beetles, functioning as
      attractants or repellents, often as synergists to compounds currently used in
      bark beetle control. Thus, these compounds could serve as valuable new agents for
      bark beetle management. However, bark beetle associations with fungi are very
      complex. Beetle behavior varies with the species of fungus, the stage of the
      beetle life cycle, the host tree quality, and probably with changes in the
      emission rate of fungal volatiles. Additional research on bark beetles and their
      symbiotic associates is necessary before the basic significance of ophiostomatoid
      fungal volatiles can be understood and their applied potential realized.

PMID- 27688001
TI  - Evaluation of bacteriocinogenic activity, safety traits and biotechnological
      potential of fecal lactic acid bacteria (LAB), isolated from Griffon Vultures
      (Gyps fulvus subsp. fulvus).
AB  - BACKGROUND: Lactic acid bacteria (LAB) are part of the gut microbiota and produce
      ribosomally synthesized antimicrobial peptides or bacteriocins with interest as
      natural food preservatives and therapeutic agents. Bacteriocin-producing LAB are
      also attractive as probiotics. Griffon vultures (Gyps fulvus subspecies fulvus)
      are scavenger birds that feed almost exclusively on carrion without suffering
      apparent ill effects. Therefore, griffon vultures might be considered a reservoir
      of bacteriocin-producing lactic acid bacteria (LAB) with potential
      biotechnological applications. RESULTS: Griffon vulture feces were screened for
      LAB with antimicrobial activity, genes encoding bacteriocins, potential virulence
      determinants, susceptibility to antibiotics, genotyping and characterization of
      bacteriocins. In this study, from 924 LAB evaluated 332 isolates (36 %) showed
      direct antimicrobial activity against Gram-positive bacteria only. The molecular
      identification of the most antagonistic 95 isolates showed that enterococci was
      the largest LAB group with antimicrobial activity (91 %) and E. faecium (40 %)
      the most identified antagonistic species. The evaluation of the presence of
      bacteriocin structural genes in 28 LAB isolates with the highest
      bacteriocinogenic activity in their supernatants determined that most
      enterococcal isolates (75 %) encoded multiple bacteriocins, being enterocin A
      (EntA) the largest identified (46 %) bacteriocin. Most enterococci (88 %) were
      resistant to multiple antibiotics. ERIC-PCR and MLST techniques permitted
      genotyping and recognition of the potential safety of the bacteriocinogenic
      enterococci. A multiple-step chromatographic procedure, determination of the N
      terminal amino acid sequence of purified bacteriocins by Edman degradation and a
      MALDI TOF/TOF tandem MS procedure permitted characterization of bacteriocins
      present in supernatants of producer cells. CONCLUSIONS: Enterococci was the
      largest LAB group with bacteriocinogenic activity isolated from griffon vulture
      feces. Among the isolates, E. faecium M3K31 has been identified as producer of
      enterocin HF (EntHF), a bacteriocin with remarkable antimicrobial activity
      against most evaluated Listeria spp. and of elevated interest as a natural food
      preservative. E. faecium M3K31 would be also considered a safe probiotic strain
      for use in animal nutrition.

PMID- 27688002
TI  - Physical activity and motivational predictors of changes in health behavior and
      health among DM2 and CAD patients.
AB  - This study tested a physical activity intervention and the self-determination
      theory (SDT) process model of health-behavior change and health among 108 adult
      patients with both diabetes mellitus type 2 (DM2) and coronary artery disease
      (CAD). Patients were randomly assigned to an organized physical activity
      intervention group (led by instructors) or a non-physical activity control group.
      At baseline and after 12 months, we measured the following: needs satisfaction,
      autonomous and controlled motivation for physical activity, perceived competence
      for physical activity and blood sugar testing, physical activity and blood sugar
      testing, body weight, glucose control (HbA1c), and self-perceptions of general
      health and vitality. The intervention produced, as hypothesized, significant
      changes in all study variables in favor of the experimental group (Cohen's d
      effect sizes: 0.23-0.72), except the non-significant result for controlled
      motivation and body weight. The data supported the SDT process model, in which
      the effect of the intervention significantly predicted indirect changes in
      behavior and health through motivation variables. Considering the moderate to
      large effects on increases in motivation, behavior, and health, promoting
      organized physical activity programs that are perceived as need-supportive may
      have important health implications for patients with DM2 and CAD.

PMID- 27688003
TI  - High Triterpenic Acids Production in Callus Cultures from Fruit Pulp of Two Apple
      Varieties.
AB  - INTRODUCTION: Very rarely fruit pulp has been used in in vitro culture to produce
      secondary metabolites useful in promoting health. OBJECTIVES: The aims of this
      work were the study of the best conditions to obtain the callus cultures from the
      pulp of two varieties of apples, Golden Delicious (GD) and "Mela Rosa
      Marchigiana" (MRM), and the quali-quantitative analysis of secondary metabolites
      produced by the two in vitro callus cultures. METHODOLOGY: Callus was induced on
      both Murashige and Skoog and Gamborg B5 media containing various combinations of
      supplements. To achieve the maximum recovery of secondary metabolites produced,
      preliminary extraction tests were carried out on GD apple culture using two
      different organic solvents (MeOH and EtOAc). The quali-quantitative analysis of
      the methanolic extract of both cultures was carried out by ESI-MSn and GC-MS
      techniques. RESULTS: The GC-MS analysis revealed the presence of triterpenic
      acids, in particular, oleanolic, ursolic, maslinic, pomolic, tormentic, corosolic
      and annurcoic acid along with a phytosterol, beta-sitosterol. In addition, GD
      callus culture produced phloridzin, absent in the MRM culture. In this last
      culture, however, the total amount of secondary metabolites was markedly higher.
      The in vivo production of these bioactive compounds were also quantified in the
      GD and MRM apple pulps. CONCLUSION: Apple pulps produced higher amounts of
      triterpenic acids in vitro than in vivo. The present work can be considered a
      method to amplify the production of important secondary metabolites which exert
      beneficial effects on human health. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27688004
TI  - Understanding the rise of Yinao in China: A commentary on the little known
      phenomenon of healthcare violence.
AB  - Yinao (healthcare disturbance) refers to violent incidents directed against
      healthcare staff and facilities for financial benefit. In China, incidences of
      Yinao are widespread and increasing, but little is known of this phenomenon in
      the wider global community. This commentary investigates the factors behind Yinao
      to achieve a deeper understanding. Causes include a lack of trust in medical
      staff, fueled by costly medical expenses; difficulties in accessing treatment;
      poor treatment outcomes; high patient expectations; a misunderstanding or
      rejection of medical ethics; misleading media reports; and a complex appeals
      process. Both doctors and nurses have been the targets of violent and distressing
      Yinao events, resulting in emotional pain, physical injury, and even death. In
      response, hospitals have established a series of preventative measures and and
      the government has increased the penalties for perpetrators of acts of Yinao. The
      situation is a salient reminder to policymakers worldwide of the importance of an
      accessible, affordable, and equitable health system.

PMID- 27688005
TI  - Magnitude-dependent and inversely-related osteogenic/chondrogenic differentiation
      of human mesenchymal stem cells under dynamic compressive strain.
AB  - Biomechanical forces have been shown to significantly affect tissue development,
      morphogenesis, pathogenesis and healing, especially in orthopaedic tissues. Such
      biological processes are critically related to the differentiation of human
      mesenchymal stem cells (hMSCs). However, the mechanistic details regarding how
      mechanical forces direct MSC differentiation and subsequent tissue formation are
      still elusive. Electrospun three-dimensional scaffolds were used to culture and
      subject hMSCs to various magnitudes of dynamic compressive strains at 5, 10, 15
      or 20% (epsilon = 0.05, 0.10, 0.15, 0.20) at a frequency of 1 Hz for 2 h daily
      for up to 28 days in osteogenic media. Gene expression of chondrogenic markers
      (ACAN, COL2A1, SOX9) and glycosaminoglycan (GAG) synthesis were upregulated in
      response to the increased magnitudes of compressive strain, whereas osteogenic
      markers (COL1A1, SPARC, RUNX2) and calcium deposition had noticeable decreases by
      compressive loading in a magnitude-dependent manner. Dynamic mechanical analysis
      showed enhanced viscoelastic modulus with respect to the increased dynamic strain
      peaking at 15%, which coincides with the maximal GAG synthesis. Furthermore,
      polarization-sensitive optical coherence tomography revealed that mechanical
      loading enhanced the alignment of extracellular matrix to the greatest level by
      15% strain as well. Overall, we show that the degree of differentiation of hMSCs
      towards osteogenic or chondrogenic lineage is inversely related, and it depends
      on the magnitude of dynamic compressive strain. These results demonstrate that
      multiphenotypic differentiation of hMSCs can be controlled by varying the strain
      regimens, providing a novel strategy to modulate differentiation specification
      and tissue morphogenesis. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27688007
TI  - Individual differences in exploratory activity relate to cognitive judgement bias
      in carpenter ants.
AB  - Emotional state may influence cognitive processes such as attention and decision
      making. A cognitive judgement bias is the propensity to anticipate either
      positive or negative consequences in response to ambiguous information. Recent
      work, mainly on vertebrates, showed that the response to ambiguous stimuli might
      change depending on an individual's affective state, which is influenced by e.g.
      the social and physical environment. However, the response to ambiguous stimuli
      could also be affected by the individual's behavioural type (personality), a
      question that has been under-investigated. We studied the link between individual
      differences in exploratory activity and the response to an ambiguous stimulus in
      the ant Camponotus aethiops. Exploratory behaviour, quantified with an open-field
      test, was variable among individuals but consistent over time within individuals.
      Individual ants learned to associate a spatial position to a reinforcement and
      another spatial position to a punishment. Once the ants had acquired this
      discrimination, cognitive judgement bias was tested with the stimulus in an
      intermediate position. Fast explorers in the open-field took significantly more
      time to approach the ambiguous stimulus compared to slow explorers, suggesting a
      negative judgement bias for fast explorers and a positive bias for slow
      explorers. This previously unknown link between individual difference in
      exploratory activity and cognitive bias in a social insect may help understanding
      the evolution and organization of social life.

PMID- 27688006
TI  - Moderate Alcohol Consumption and Chronic Disease: The Case for a Long-Term Trial.
AB  - Drinking within recommended limits is highly prevalent in much of the world, and
      strong epidemiological associations exist between moderate alcohol consumption
      and risk of several major chronic diseases, including coronary heart disease,
      diabetes, and breast cancer. In many cases, plausible biological mediators for
      these associations have been identified in randomized trials, but gold standard
      evidence that moderate drinking causes or prevents any chronic disease remains
      elusive and important concerns about available evidence have been raised.
      Although long-term randomized trials to test the observed associations have been
      termed impossible, clinical investigators have now successfully completed
      randomized trials of complex nutritional interventions in a variety of settings,
      along with trials of alcohol consumption itself of up to 2 years duration. The
      successful completion of these trials suggests that objections to the execution
      of a full-scale, long-term clinical trial of moderate drinking on chronic disease
      are increasingly untenable. We present potential lessons learned for such a trial
      and discuss key features to maximize its feasibility and value.

PMID- 27688008
TI  - Resection of tumors of the third ventricle involving the hypothalamus: effects on
      body mass index using a dedicated surgical approach.
AB  - Resection of large lesions growing into the third ventricle is considered
      nowadays still a demanding surgery, due to the high risk of severe endocrine and
      neurological complications. Some neurosurgical approaches were considered in the
      past the procedures of choice to access the third ventricle, however they were
      burden by endocrine and neurological consequences, like memory loss and epilepsy.
      We report here the endocrine and functional results in a series of patients
      operated with a recently developed approach specifically tailored for the
      resection of large lesions growing into the third ventricle. Authors conducted a
      retrospective analysis on 10 patients, operated between 2011 and 2012, for the
      resection of large tumors growing into the third ventricle. Total resection was
      achieved in all patients. No perioperative deaths were recorded and all patients
      were alive after the follow-up. One year after surgery 8/10 patients had an
      excellent outcome with a Karnofsky Performance Status of 100 and a Glasgow
      Outcome score of 5, with 8 patients experiencing an improvement of the Body Mass
      Index. Modern neurosurgery allows a safe and effective treatment of large lesions
      growing into the third ventricle with a postoperative good functional status.

PMID- 27688009
TI  - 10-year follow-up study comparing primary medical vs. surgical therapy in women
      with prolactinomas.
AB  - While dopamine-agonists are the first-line approach in treating prolactinomas,
      surgery can be considered in selected cases besides non-responders or patients
      with dopamine-agonist intolerance. The aim of the present study was to compare
      the long-term outcome in women with prolactinomas treated primarily either
      surgically or medically who had not had prior dopamine-agonist treatment.
      Retrospective case-note study of all consecutive women with prolactinomas
      primarily managed with medical therapy or surgery in a tertiary referral centre.
      The clinical, biochemical, and radiological responses to first-line treatment at
      early and long-term follow-up were analysed. The primary therapeutic strategy was
      dopamine-agonists for 36 (34 %) and surgery for 71 (66 %) of the women. Baseline
      clinical and biochemical characteristics were not significantly different between
      the primary surgical and medical cohort. Median follow-up time was 90 months
      (range 13-408). Following primary treatment, prolactin level significantly
      decreased in both cohorts, on average to 13.5 ug/L (IQR 7-21; p < 0.001), and was
      within the normal range in 82 % of all patients. No women in the surgical cohort
      demonstrated permanent sequelae and morbidity was low. At final follow-up,
      control of hyperprolactinaemia required dopamine-agonist therapy in 64 % of women
      who had undergone primary medical therapy vs. 32 % of those who had primary
      surgical therapy (p = 0.003). Logistic regression revealed that the primary
      therapeutic strategy, but not adenoma size, was an independent risk factor for
      long-term dependence on dopamine-agonists. The present data indicate that in a
      dedicated tertiary referral centre, long-term control of hyperprolactinaemia in
      women with prolactinomas is high. In selected cases, a primary neurosurgical
      approach might at least be interdisciplinarily discussed with the primary goal of
      minimizing long-term dependence on dopamine-agonists.

PMID- 27688010
TI  - Comparison of the therapeutic effects of prednisolone and nonsteroidal anti
      inflammatory drugs in patients with subacute thyroiditis.
AB  - Subacute thyroiditis is a transient inflammatory thyroid disease of unknown
      etiology. The primary goal for treatment is to mitigate inflammation. The aim of
      this retrospective study was to compare the therapeutic effects of prednisolone
      and nonsteroidal anti-inflammation drugs in patients with subacute thyroiditis.
      In this study, 53 consecutive Japanese patients who had been diagnosed with were
      referred to our hospital for further management. After excluding 11 patients (9
      did not need treatment, 2 did not meet the criteria for diagnosis of subacute
      thyroiditis), the remaining 42 patients were treated either with prednisolone (n
      = 25) or loxoprofen (n = 17). We compared the time periods required for
      resolution of clinical symptoms and signs and normalization of thyroid function
      between the two groups. The mean dose of prednisolone was 15.0 (range, 14-16)
      mg/day and that of loxoprofen was 180 mg/day. The time period to normalization of
      thyroid function was comparable between the prednisolone and loxoprofen groups
      (25, 18-36, vs 32, 21-39 days, p = 0.388). However, the time period for
      resolution of symptoms was shorter under prednisolone than loxoprofen (7, 7-12
      days, vs 21, 14-32 days, p < 0.001). Prednisolone treatment of patients with
      subacute thyroiditis was superior to nonsteroidal anti-inflammation drugs with
      regard to resolution of symptoms.

PMID- 27688011
TI  - Frequency, pattern, and outcome of recurrences after gamma knife radiosurgery for
      pituitary adenomas.
AB  - Gamma Knife radiosurgery is often used in pituitary adenomas. Aim of our study is
      to describe the characteristics and long-term outcome of patients with adenoma
      recurrence after Gamma Knife radiosurgery. We conducted a retrospective analysis
      of patients with pituitary adenoma treated by Gamma Knife radiosurgery between
      1994 and 2014. Tumor recurrence was labeled as "in field" when the tumor growth
      occurred adjacent or within the prescribed isodose, whereas it was classified as
      "out of field" when the tumor growth occurred outside the prescribed isodose.
      Five hundred forty-three patients were included, 272 (50.1 %) had a
      nonfunctioning pituitary adenoma (NFPA) and 271 (49.9 %) patients had a hormone
      secreting-pituitary adenoma. The median follow-up after GKRS was 78 months (IQR,
      36-125 months). Thirty-nine patients (7.2 %) had recurrence of disease and it was
      more frequent in patients with NFPA than in patients with hormone secreting
      adenomas (9.6 % vs. 4.8 %). The 10-yr progression-free survival in patients with
      NFPA was 78.7 % (95 % CI 69.5 - 87.9 %), as compared with 93.3 % (95 % CI 89.3 -
      97.3 %; p < 0.01) in hormone secreting adenomas. Tumor recurrence was "in field"
      in 17 cases (43.6 %) and "out of field" in 22 cases (56.4 %). Seven of the 39
      patients with recurrence died despite further treatments. Six of these patients
      had an "in field" recurrence. Recurrence of a pituitary adenoma after GKRS may
      occur several years after initial treatment. Distinction between "in field" and
      "out of field" tumor recurrence probably reflects two different
      pathophysiological mechanisms and may have prognostic importance.

PMID- 27688012
TI  - Comment on "Long-term exposure to electromagnetic radiation from mobile phones
      and Wi-Fi devices decreases plasma prolactin, progesterone, and estrogen levels
      but increases uterine oxidative stress in pregnant rats and their offspring".

PMID- 27688014
TI  - Fortifying p53 - beyond Mdm2 inhibitors.

PMID- 27688015
TI  - Contextual adversity, telomere erosion, pubertal development, and health: Two
      models of accelerated aging, or one?
AB  - Two independent lines of inquiry suggest that growing up under conditions of
      contextual adversity (e.g., poverty and household chaos) accelerates aging and
      undermines long-term health. Whereas work addressing the developmental origins of
      health and disease highlights accelerated-aging effects of contextual adversity
      on telomere erosion, that informed by an evolutionary analysis of reproductive
      strategies highlights such effects with regard to pubertal development (in
      females). That both shorter telomeres early in life and earlier age of menarche
      are associated with poor health later in life raises the prospect, consistent
      with evolutionary life-history theory, that these two bodies of theory and
      research are tapping into the same evolutionary-developmental process whereby
      longer term health costs are traded off for increased probability of reproducing
      before dying via a process of accelerated aging. Here we make the case for such a
      claim, while highlighting biological processes responsible for these effects, as
      well as unknowns in the epigenetic equation that might instantiate these
      contextually regulated developmental processes.

PMID- 27688013
TI  - Effects of the single and combined treatment with dopamine agonist, somatostatin
      analog and mTOR inhibitors in a human lung carcinoid cell line: an in vitro
      study.
AB  - Somatostatin analogues and mTOR inhibitors have been used as medical therapy in
      lung carcinoids with variable results. No data are available on dopamine agonists
      as treatment for lung carcinoids. The main aim of the current study was to
      evaluate the effect of the combined treatment of somatostatin analogue octreotide
      and the dopamine agonist cabergoline with mTOR inhibitors in an in vitro model of
      typical lung carcinoids: the NCI-H727 cell line. In NCI-H727 cell line, reverse
      transcriptase-quantitative polymerase chain reaction and immunofluorescence were
      assessed to characterize the expression of the somatostatin receptor 2 and 5,
      dopamine receptor 2 and mTOR pathway components. Fifteen typical lung carcinoids
      tissue samples have been used for somatostatin receptor 2, dopamine receptor 2,
      and the main mTOR pathway component p70S6K expression and localization by
      immunohistochemistry. Cell viability, fluorescence-activated cell sorting
      analysis and western blot have been assessed to test the pharmacological effects
      of octreotide, cabergoline and mTOR inhibitors, and to evaluate the activation of
      specific cell signaling pathways in NCI-H727 cell line. NCI-H727 cell line
      expressed somatostatin receptor 2, somatostatin receptor 5 and dopamine receptor
      2 and all mTOR pathway components at messenger and protein levels. Somatostatin
      receptor 2, dopamine receptor 2, and p70S6K (non phosphorylated and
      phosphorylated) proteins were expressed in most typical lung carcinoids tissue
      samples. Octreotide and cabergoline did not reduce cell viability as single
      agents but, when combined with mTOR inhibitors, they potentiate mTOR inhibitors
      effect after long-term exposure, reducing Akt and ERK phosphorylation, mTOR
      escape mechanisms, and increasing the expression DNA-damage-inducible transcript
      4, an mTOR suppressor. In conclusion, the single use of octreotide and
      cabergoline is not sufficient to block cell viability but the combined approach
      of these agents with mTOR inhibitors might reduce the mTOR inhibitors-induced
      escape mechanisms and/or activate the endogenous mTOR suppressor, potentiating
      the effect of the mTOR inhibitors in an in vitro model of typical lung
      carcinoids.

PMID- 27688016
TI  - Probiotics for the Prevention of Pediatric Antibiotic-Associated Diarrhea.
AB  - : Goldenberg JZ, Lytvyn L, Steurich J, Parkin P, Mahant S, Johnston BC.
      Probiotics for the prevention of pediatric antibiotic-associated
      diarrhea.Cochrane Database Syst Rev2015, Issue 12. Art. No.: CD004827.
      http://dx.doi.org/10.1002/14651858.CD004827.pub4. BACKGROUND: Antibiotics are
      frequently prescribed in children. They alter the microbial balance within the
      gastrointestinal tract, commonly resulting in antibiotic-associated diarrhea
      (AAD). Probiotics may prevent AAD via restoration of the gut microflora.
      OBJECTIVES: The primary objectives were to assess the efficacy and safety of
      probiotics (any specified strain or dose) used for the prevention of AAD in
      children. SEARCH METHODS: MEDLINE, EMBASE, CENTRAL, CINAHL, AMED, and the Web of
      Science (inception to November 2014) were searched along with specialized
      registers including the Cochrane IBD/FBD review group, CISCOM (Centralized
      Information Service for Complementary Medicine), NHS Evidence, the International
      Bibliographic Information on Dietary Supplements, as well as trial registries.
      Letters were sent to authors of included trials, nutraceutical and pharmaceutical
      companies, and experts in the field requesting additional information on ongoing
      or unpublished trials. Conference proceedings, dissertation abstracts, and
      reference lists from included and relevant articles were also searched. SELECTION
      CRITERIA: Randomized, parallel, controlled trials in children (0-18 years)
      receiving antibiotics, that compare probiotics to placebo, active alternative
      prophylaxis, or no treatment and measure the incidence of diarrhea secondary to
      antibiotic use were considered for inclusion. DATA COLLECTION AND ANALYSIS: Study
      selection, data extraction, and methodological quality assessment using the risk
      of bias instrument were conducted independently and in duplicate by two authors.
      Dichotomous data (incidence of diarrhea and adverse events) were combined using a
      pooled risk ratio (RR) or risk difference (RD), and continuous data (mean
      duration of diarrhea and mean daily stool frequency) as mean difference (MD),
      along with their corresponding 95% confidence interval (95% CI). For overall
      pooled results on the incidence of diarrhea, sensitivity analyses included
      available case versus extreme-plausible analyses and random- versus fixed-effect
      models. To explore possible explanations for heterogeneity, a priori subgroup
      analysis was conducted on probiotic strain, dose, definition of antibiotic
      associated diarrhea, and risk of bias. We also conducted post hoc subgroup
      analyses by patient diagnosis, single versus multi-strain, industry sponsorship,
      and inpatient status. The overall quality of the evidence supporting the outcomes
      was evaluated using the GRADE criteria. MAIN RESULTS: Overall, 23 studies (3938
      participants) met the inclusion criteria. Trials included treatment with either
      Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp.,
      Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., or Streptococcus
      spp., alone or in combination. Eleven studies used a single-strain probiotic,
      four combined two probiotic strains, three combined three probiotic strains, one
      combined four probiotic strains, two combined seven probiotic strains, one
      included ten probiotic strains, and one study included two probiotic arms that
      used three and two strains, respectively. The risk of bias was determined to be
      high or unclear in 13 studies and low in 10 studies. Available case (patients who
      did not complete the studies were not included in the analysis) results from
      22/23 trials reporting on the incidence of diarrhea show a precise benefit from
      probiotics compared to active, placebo, or no treatment control. The incidence of
      AAD in the probiotic group was 8% (163/1992) compared to 19% (364/1906) in the
      control group (RR = 0.46; 95% CI: 0.35-0.61; I2 = 55%, 3898 participants). A
      GRADE analysis indicated that the overall quality of the evidence for this
      outcome was moderate. This benefit remained statistically significant in an
      extreme-plausible (60% of children lost to follow-up in probiotic group and 20%
      lost to follow-up in the control group had diarrhea) sensitivity analysis, where
      the incidence of AAD in the probiotic group was 14% (330/2294) compared to 19%
      (426/2235) in the control group (RR = 0.69; 95% CI: 0.54-0.89; I2 = 63%, 4529
      participants). None of the 16 trials (n = 2455) that reported on adverse events
      documented any serious adverse events attributable to probiotics. Meta-analysis
      excluded all but an extremely small non-significant difference in adverse events
      between treatment and control (RD = 0.00, 95% CI: -0.01 to 0.01). The majority of
      adverse events were in placebo, standard care, or no treatment group. Adverse
      events reported in the studies include rash, nausea, gas, flatulence, abdominal
      bloating, abdominal pain, vomiting, increased phlegm, chest pain, constipation,
      taste disturbance, and low appetite. AUTHORS' CONCLUSIONS: Moderate quality
      evidence suggests a protective effect of probiotics in preventing AAD. Our pooled
      estimate suggests a precise (RR 0.46; 95% CI: 0.35-0.61) probiotic effect with an
      NNT of 10. Among the various probiotics evaluated, Lactobacillus rhamnosus or
      Saccharomyces boulardii at 5-40 billion colony-forming units/day may be
      appropriate given the modest NNT and the likelihood that adverse events are very
      rare. It is premature to draw conclusions about the efficacy and safety of other
      probiotic agents for pediatric AAD. Although no serious adverse events were
      observed among otherwise healthy children, serious adverse events have been
      observed in severely debilitated or immunocompromised children with underlying
      risk factors including central venous catheter use and disorders associated with
      bacterial/fungal translocation. Until further research has been conducted,
      probiotic use should be avoided in pediatric populations at risk for adverse
      events. Future trials would benefit from a standard and valid outcomes to measure
      AAD.

PMID- 27688017
TI  - "The Program Affects Me 'Cause it Gives Away Stress": Urban Students' Qualitative
      Perspectives on Stress and a School-Based Mindful Yoga Intervention.
AB  - CONTEXT: School-based mindfulness and yoga studies generally measure stress
      related outcomes using quantitative measures. OBJECTIVE: This study answers the
      following research questions: How do youth define stress and in what ways, if
      any, was a mindful yoga intervention helpful to youth during stress experiences?
      DESIGN AND SUBJECTS: To explore youths' own perspectives on stress, stressors in
      youths' lives, and perceived changes in responses to stress post-intervention, we
      conducted focus group discussions with 22 middle school students from low-income
      urban communities following a 16-week mindful yoga intervention. RESULTS: Using
      thematic analysis, the following three themes emerged: (1) youth conflated stress
      with negative emotions; (2) peer and family conflicts were common stressors; and
      (3) youth reported improved impulse control and emotional regulation following
      the intervention. Study findings have implications for refining intervention
      content (e.g., discussions of stress), as well as informing the selection and
      development of quantitative measures for future research on stress and stress
      responses in urban youth.

PMID- 27688018
TI  - Improved detection of soma location and morphology in fluorescence microscopy
      images of neurons.
AB  - BACKGROUND: Automated detection and segmentation of somas in fluorescent images
      of neurons is a major goal in quantitative studies of neuronal networks,
      including applications of high-content-screenings where it is required to
      quantify multiple morphological properties of neurons. Despite recent advances in
      image processing targeted to neurobiological applications, existing algorithms of
      soma detection are often unreliable, especially when processing fluorescence
      image stacks of neuronal cultures. NEW METHOD: In this paper, we introduce an
      innovative algorithm for the detection and extraction of somas in fluorescent
      images of networks of cultured neurons where somas and other structures exist in
      the same fluorescent channel. Our method relies on a new geometrical descriptor
      called Directional Ratio and a collection of multiscale orientable filters to
      quantify the level of local isotropy in an image. To optimize the application of
      this approach, we introduce a new construction of multiscale anisotropic filters
      that is implemented by separable convolution. RESULTS: Extensive numerical
      experiments using 2D and 3D confocal images show that our automated algorithm
      reliably detects somas, accurately segments them, and separates contiguous ones.
      COMPARISON WITH EXISTING METHODS: We include a detailed comparison with state-of
      the-art existing methods to demonstrate that our algorithm is extremely
      competitive in terms of accuracy, reliability and computational efficiency.
      CONCLUSIONS: Our algorithm will facilitate the development of automated platforms
      for high content neuron image processing. A Matlab code is released open-source
      and freely available to the scientific community.

PMID- 27688019
TI  - Self-immolation: A cultural view.

PMID- 27688020
TI  - Systemic GM-CSF Recruits Effector T Cells into the Tumor Microenvironment in
      Localized Prostate Cancer.
AB  - Granulocytic-macrophage colony-stimulating factor (GM-CSF) is used as an adjuvant
      in cancer vaccine trials and has the potential to enhance antitumor efficacy with
      immunotherapy; however, its immunologic effects are not fully understood. Here,
      we report results from a phase I study of neoadjuvant GM-CSF in patients with
      localized prostate cancer undergoing radical prostatectomy. Patients received
      subcutaneous injections of GM-CSF (250 MUg/m2/day) daily for 2 weeks (cohort 1; n
      = 6), 3 weeks (cohort 2; n = 6), or 4 weeks (cohort 3; n = 6). Treatment was well
      tolerated with all grade 1 or 2 adverse events. Two patients had a decline in
      prostate-specific antigen (PSA) of more than 50%. GM-CSF treatment increased the
      numbers of circulating mature myeloid dendritic cells, proliferating conventional
      CD4 T cells, proliferating CD8 T cells, and to a lesser magnitude FoxP3+
      regulatory CD4 T cells. Although GM-CSF treatment did not augment antigen
      presenting cell localization to the prostate, treatment was associated with
      recruitment of CD8+ T cells to the tumor. These results suggest that systemic GM
      CSF can modulate T-cell infiltration in the tumor microenvironment. Cancer
      Immunol Res; 4(11); 948-58. (c)2016 AACR.

PMID- 27688022
TI  - Early group psychoeducation for bipolar disorder.

PMID- 27688021
TI  - Clinical effectiveness and acceptability of structured group psychoeducation
      versus optimised unstructured peer support for patients with remitted bipolar
      disorder (PARADES): a pragmatic, multicentre, observer-blind, randomised
      controlled superiority trial.
AB  - BACKGROUND: Group psychoeducation is a low-cost National Institute for Health and
      Care Excellence-recommended treatment for bipolar disorder. However, the clinical
      effectiveness and acceptability of this intervention are unclear compared with
      unstructured peer support matched for delivery and aim of treatment, and for
      previous bipolar history. We aimed to assess the clinical effectiveness and
      acceptability of structured group psychoeducation versus optimised unstructured
      peer support for patients with remitted bipolar disorder. METHODS: We did this
      pragmatic, multicentre, parallel-group, observer-blind, randomised controlled
      superiority trial at eight community sites in two regions in England.
      Participants aged 18 years or older with bipolar disorder and no episode in the
      preceding 4 weeks were recruited via self-referral or secondary care referral.
      Participants were individually randomly assigned (1:1), via a computer-generated
      stochastic allocation sequence, to attend 21 2-h weekly sessions of either
      structured group psychoeducation or optimised unstructured peer support.
      Randomisation was minimised by number of previous episodes (one to seven, eight
      to 19, or >=20) and stratified by clinical site. Outcome assessors were masked to
      group allocation. The primary outcome was time from randomisation to next bipolar
      episode, with planned moderator analysis of number of previous bipolar episodes
      and qualitative interview of participant experience. We did analysis by intention
      to treat. This trial is registered with the International Standard Randomised
      Controlled Trial registry, number ISRCTN62761948. FINDINGS: Between Sept 28,
      2009, and Jan 9, 2012, we randomly assigned 304 participants to receive
      psychoeducation (n=153) or peer support (n=151); all (100%) participants had
      complete primary outcome data. Attendance at psychoeducation groups was higher
      than at peer-support groups (median 14 sessions [IQR three to 18] vs nine
      sessions [two to 17]; p=0.026). At 96 weeks, 89 (58%) participants in the
      psychoeducation group had experienced a next bipolar episode compared with 98
      (65%) participants in the peer-support group; time to next bipolar episode did
      not differ between groups (hazard ratio [HR] 0.83, 95% CI 0.62-1.11; p=0.217).
      Planned moderator analysis showed that psychoeducation was most beneficial in
      participants with few (one to seven) previous bipolar episodes (chi2; HR 0.28,
      95% CI 0.12-0.68; p=0.034). Four (1%) participants (one in the psychoeducation
      group and three in the peer-support group) died during follow-up; these deaths
      were deemed unrelated to the study interventions or procedures. INTERPRETATION:
      Structured group psychoeducation was no more clinically effective than similarly
      intensive unstructured peer support, but was more acceptable and improved outcome
      in participants with fewer previous bipolar episodes. Optimum provision of
      structured psychological interventions, such as group psychoeducation, early in
      the course of bipolar disorder might have important benefits on the course of
      illness, and merits further research. FUNDING: National Institute for Health
      Research.

PMID- 27688023
TI  - Crystal structure of the enzyme-product complex reveals sugar ring distortion
      during catalysis by family 63 inverting alpha-glycosidase.
AB  - Glycoside hydrolases are divided into two groups, known as inverting and
      retaining enzymes, based on their hydrolytic mechanisms. Glycoside hydrolase
      family 63 (GH63) is composed of inverting alpha-glycosidases, which act mainly on
      alpha-glucosides. We previously found that Escherichia coli GH63 enzyme, YgjK,
      can hydrolyze 2-O-alpha-d-glucosyl-d-galactose. Two constructed glycosynthase
      mutants, D324N and E727A, which catalyze the transfer of a beta-glucosyl fluoride
      donor to galactose, lactose, and melibiose. Here, we determined the crystal
      structures of D324N and E727A soaked with a mixture of glucose and lactose at 1.8
      and 2.1-A resolutions, respectively. Because glucose and lactose molecules are
      found at the active sites in both structures, it is possible that these
      structures mimic the enzyme-product complex of YgjK. A glucose molecule found at
      subsite -1 in both structures adopts an unusual 1S3 skew-boat conformation.
      Comparison between these structures and the previously determined enzyme
      substrate complex structure reveals that the glucose pyranose ring might be
      distorted immediately after nucleophilic attack by a water molecule. These
      structures represent the first enzyme-product complex for the GH63 family, as
      well as the structurally-related glycosidases, and it may provide insight into
      the catalytic mechanism of these enzymes.

PMID- 27688024
TI  - A pilot cluster randomised trial to assess the effect of a structured
      communication approach on quality of life in secure mental health settings: The
      Comquol Study.
AB  - BACKGROUND: There is a lack of research in forensic settings examining
      therapeutic relationships. A structured communication approach, placing patients'
      perspectives at the heart of discussions about their care, was used to improve
      patients' quality of life in secure settings. The objectives were to: * Establish
      the feasibility of the trial design * Determine the variability of the outcomes
      of interest * Estimate the costs of the intervention * If necessary, refine the
      intervention METHODS: A pilot cluster randomised controlled trial was conducted.
      Data was collected from July 2012 to January 2015 from participants in 6 medium
      secure in-patient services in London and Southern England. 55 patients and 47
      nurses were in the intervention group with 57 patients and 45 nurses in the
      control group. The intervention comprised 6 nurse-patient meetings over a 6 month
      period. Patients rated their satisfaction with a range of domains followed by
      discussions on improving patient identified problems. Assessments took place at
      baseline, 6 months, and 12 months. Participants were not blind to their allocated
      group. The primary outcome was self-reported quality of life collected by a
      researcher blind to participants' allocation status. RESULTS: The randomisation
      procedures and intervention approach functioned well. The measures used were
      understood by the participants and gave relevant outcome information. The
      response rates were good with low patient withdrawal rates. The quality of life
      estimated treatment effect was 0.2 (95 % CI: -0.4 to 0.8) at 6 months and 0.4 (95
      % CI: -0.3 to 1.1) indicating the likely extreme boundaries of effect in the main
      trial. The estimated treatment effect of the primary outcome is clinically
      important, and a positive effect of the intervention is not ruled out. The
      estimate of the ICC for the primary outcome at 6 and 12 months was 0.04 (0.00 to
      0.17) and 0.05 (0.00 to 0.18). The cost of the intervention was L529 per patient.
      CONCLUSIONS: The trial design was viable as the basis for a full-scale trial. A
      full trial is justified to estimate the effect of the intervention with greater
      certainty. The variability of the outcomes could be used to calculate numbers
      needed for a full-scale trial. Ratings of need for therapeutic security may be
      useful in any future study. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN34145189 . Retrospectively registered 22 June 2012.

PMID- 27688025
TI  - Completeness of Spontaneous Adverse Drug Reaction Reports Sent by General
      Practitioners to a Regional Pharmacovigilance Centre: A Descriptive Study.
AB  - INTRODUCTION: Spontaneous reporting of adverse drug reactions (ADRs) remains the
      cornerstone of postmarketing drug safety surveillance (pharmacovigilance);
      however, one of its main limitations is incomplete data, thus limiting
      conclusions about causality assessment. OBJECTIVE: The primary aim of this study
      was to assess the completeness of ADR reports sent by general practitioners (GPs)
      to regional pharmacovigilance centres and the secondary objective was to identify
      factors associated with complete ADR reports. METHODS: All ADR reports sent by
      GPs to the Midi-Pyrenees Regional Pharmacovigilance Center (Toulouse, France)
      from 1 January 2010 to 31 December 2013 were reviewed. Healthcare professionals
      and patients can forward an ADR using either an online form through the
      Pharmacology Information Bulletin website ( http://www.bip31.fr ) or
      'traditional' ADR reports (i.e. email, letter or fax). According to information
      provided in ADR reports (i.e. patient identification, ADR, date of occurrence,
      clinical description, drugs, etc.), reports were classified into three groups:
      'well-documented', 'slightly documented' or 'poorly documented'. A multivariate
      logistic regression was performed to investigate potential factors associated
      with a 'well-documented' ADR report. RESULTS: During the study period, 613 ADR
      reports were analysed. Among these reports, only 12.7 % were classified as 'well
      documented', 68.5 % as 'slightly documented' and 18.8 % as 'poorly documented'.
      An association between a 'well-documented' ADR report and its 'seriousness' was
      found (odds ratio = 1.70 [95 % CI 1.04-2.76], p = 0.01). No association between
      report completeness ('well-documented' report) and GP practice location or mode
      of ADR reporting was found. CONCLUSIONS: The study shows that only one out of
      eight ADR reports from GPs was 'well-documented'. Therefore, it appears to be
      important to promote further information being available regarding the data
      required in ADR reports to optimise the evaluation of drug causality.

PMID- 27688026
TI  - Estimating Herbal Product Authentication and Adulteration in India Using a
      Vouchered, DNA-Based Biological Reference Material Library.
AB  - INTRODUCTION: India is considered the 'medicinal garden' of the world, with 8000
      medicinal plants of which 960 are commercial species that are traded nationally
      and globally. Although scientific studies estimate herbal product adulteration as
      42-66 % in North America, India does not have any published marketplace studies
      and subsequent estimates of adulteration in an industry facing considerable
      supply demands. OBJECTIVES: The goal of this project is to provide an initial
      assessment of herbal product authentication and adulteration in the marketplace
      in India by (1) developing a biological reference material (BRM) herbal DNA
      library for Indian herbal species using DNA barcode regions (ITS2 and rbcL) in
      order to facilitate accurate species resolution when testing the herbal products;
      and (2) assessing herbal product identification using our BRM library; and (3)
      comparing the use of our BRM library to identify herbal products with that of
      GenBank. METHODS: A BRM herbal DNA library consisting of 187 herbal species was
      prepared to authenticate the herbal products within India. Ninty-three herbal
      products representing ten different companies were procured from local stores
      located at Coimbatore, India. These samples were subjected to blind testing for
      authenticity using the DNA barcode regions rbcL and ITS2. RESULTS: The results
      indicate that 40 % of the products tested are authentic, and 60 % of the products
      may be adulterated (i.e. contained species of plants not listed on the product
      labels). The adulterated samples included contamination (50 %), substitution (10
      %) and fillers (6 %). Our BRM library provided a 100 % Basic Local Alignment
      Search Tool (BLAST) match for all species, whereas the GenBank match was 64 %.
      CONCLUSIONS: Our findings suggest that most Indian herbal medicinal products are
      essentially mixed with one or a few other herbs that could lessen the therapeutic
      activity of the main ingredients. We do not recommend the use of GenBank to
      identify herbal products because the use of this non-curated and/or vouchered
      database will result in inaccurate species identification. These DNA-based tools
      provide a scientific foundation for herbal pharmacovigilance to ensure the safety
      and efficacy of natural drugs. This study provides curated BRMs that will
      underpin innovations in molecular diagnostic biotechnology, which will soon
      provide more robust estimates of adulteration and commercial tools that will
      strengthen due diligence in quality assurance within the herbal industry.

PMID- 27688027
TI  - Role of glypican-1 in endothelial NOS activation under various steady shear
      stress magnitudes.
AB  - Blood flow patterns in proatherogenic and antiatherogenic regions are rather
      different. We hypothesize that the laminar flow with steady shear stress
      increased nitric oxide (NO) bioavailability while disturbed flow with low shear
      stress reduced it, which is mediating by glypican-1. Thus, we detected the
      expression of glypican-1 under different shear stress magnitudes, and tested
      whether the magnitude of shear stress determines the level of endothelial NO
      synthase (eNOS) via glypican-1 by using phosphatidylinositol phospholipase C (PI
      PLC). Results revealed that the expression of glypican-1 depends on the magnitude
      and duration of shear stress loading. Activation of eNOS in HUVECs is
      downregulated by 4dyn/cm2 of shear stress, but is upregulated by 15dyn/cm2.
      Removal of glypican-1 significantly suppressed the 15dyn/cm2 shear stress-induced
      eNOS activity, and further reduced the 4dyn/cm2-inhibited eNOS activity.
      Therefore, eNOS activation depends on shear stress magnitudes and is mediated by
      glypican-1. The role of glypican-1 in mediating the eNOS activation under shear
      stress might involve in protecting the endothelial function against disturbed
      flow and enhancing the sensitive of the endothelial cell to laminar flow,
      supporting a potential role of glypican-1 against atherosclerosis.

PMID- 27688029
TI  - Evaluation of the necessity for chest drain placement following thoracoscopic
      wedge resection.
AB  - PURPOSE: To evaluate the outcomes of patients who underwent thoracoscopic wedge
      resection without chest drain placement. METHODS: The subjects of this
      retrospective study were 89 patients, who underwent thoracoscopic wedge resection
      at our hospital between January, 2013 and July, 2015. A total of 45 patients
      whose underlying condition did not meet the following criteria were assigned to
      the "chest drain placement group" (group A): peripheral lesions, healthy lung
      parenchyma, no intraoperative air leaks, hemorrhage or effusion accumulation, and
      no pleural adhesion. The other 44 patients whose underlying condition met the
      criteria were assigned to the "no chest drain placement group" (group B). Patient
      characteristics, specimen data, and postoperative conditions were analyzed and
      compared between the groups. RESULTS: Group A patients had poorer forced
      expiratory volume in one second (FEV1) values, less normal spirometric results,
      significantly higher resected lung volume, a greater maximum tumor-pleura
      distance, and a larger maximum tumor size. They also had a longer postoperative
      hospital stay. There was no difference between the two groups in postoperative
      complications. CONCLUSIONS: Avoiding chest drain placement after a thoracoscopic
      wedge resection appears to be safe and beneficial for patients who have small
      peripheral lesions and healthy lung parenchyma.

PMID- 27688028
TI  - Early-stage heart failure with preserved ejection fraction in the pig: a
      cardiovascular magnetic resonance study.
AB  - BACKGROUND: The hypertensive deoxy-corticosterone acetate (DOCA)-salt-treated pig
      (hereafter, DOCA pig) was recently introduced as large animal model for early
      stage heart failure with preserved ejection fraction (HFpEF). The aim of the
      present study was to evaluate cardiovascular magnetic resonance (CMR) of DOCA
      pigs and weight-matched control pigs to characterize ventricular, atrial and
      myocardial structure and function of this phenotype model. METHODS: Five
      anesthetized DOCA and seven control pigs underwent 3 T CMR at rest and during
      dobutamine stress. Left ventricular/atrial (LV/LA) function and myocardial mass
      (LVMM), strains and torsion were evaluated from (tagged) cine imaging. 4D phase
      contrast measurements were used to assess blood flow and peak velocities,
      including transmitral early-diastolic (E) and myocardial tissue (E') velocities
      and coronary sinus blood flow. Myocardial perfusion reserve was estimated from
      stress-to-rest time-averaged coronary sinus flow. Global native myocardial T1
      times were derived from prototype modified Look-Locker inversion-recovery (MOLLI)
      short-axis T1 maps. After in-vivo measurements, transmural biopsies were
      collected for stereological evaluation including the volume fractions of
      interstitium (VV(int/LV)) and collagen (VV(coll/LV)). Rest, stress, and stress-to
      rest differences of cardiac and myocardial parameters in DOCA and control animals
      were compared by t-test. RESULTS: In DOCA pigs LVMM (p < 0.001) and LV wall
      thickness (end-systole/end-diastole, p = 0.003/p = 0.007) were elevated. During
      stress, increase of LV ejection-fraction and decrease of end-systolic volume
      accounted for normal contractility reserves in DOCA and control pigs. Rest-to
      stress differences of cardiac index (p = 0.040) and end-diastolic volume (p =
      0.042) were documented. Maximal (p = 0.042) and minimal (p = 0.012) LA volumes in
      DOCA pigs were elevated at rest; total LA ejection-fraction decreased during
      stress (p = 0.006). E' was lower in DOCA pigs, corresponding to higher E/E' at
      rest (p = 0.013) and stress (p = 0.026). Myocardial perfusion reserve was reduced
      in DOCA pigs (p = 0.031). T1-times and VV(int/LV) did not differ between groups,
      whereas VV(coll/LV) levels were higher in DOCA pigs (p = 0.044). CONCLUSIONS: LA
      enlargement, E' and E/E' were the markers that showed the most pronounced
      differences between DOCA and control pigs at rest. Inadequate increase of
      myocardial perfusion reserve during stress might represent a metrics for early
      stage HFpEF. Myocardial T1 mapping could not detect elevated levels of myocardial
      collagen in this model. TRIAL REGISTRATION: The study was approved by the local
      Bioethics Committee of Vienna, Austria (BMWF-66.010/0091-II/3b/2013).

PMID- 27688030
TI  - Association between the participation of board-certified surgeons in
      gastroenterological surgery and operative mortality after eight
      gastroenterological procedures.
AB  - PURPOSE: The aim of this study is to evaluate the association between the
      participation of board-certified surgeons in gastroenterological surgery (BCS-Gs)
      and the surgical outcomes of gastroenterological surgery. METHODS: Data from the
      National Clinical Database on patients who underwent eight major
      gastroenterological procedures were analyzed retrospectively. First, the ratio of
      cases in which BCS-G were involved to the total cases was calculated for each
      procedure, and the impact of BCS-G involvement on surgical outcome was assessed
      by comparing mortality rates in the group with BCS-G involvement vs. the group
      without BCS-G involvement. Second, the differences in the observed/expected ratio
      were assessed among four hospital categories according to the available BCS-G
      number. Finally, the impact of the hospital BCS-G number on mortality was
      evaluated. RESULTS: The ratio of BCS-G involvement ranged from 59.0 % for acute
      diffuse peritonitis to 89.1 % for hepatectomy, and the mortality rate was
      significantly lower for three procedures when BCS-Gs participated as the operator
      or assistant. The observed/expected ratio of hospitals with four or more BCS-Gs
      was less than 1.0 for all the procedures assessed. A multivariable logistic
      regression model showed that the hospital BCS-G number was a predictor of
      operative mortality. CONCLUSIONS: BCS-Gs contribute to favorable outcomes of
      gastroenterological surgery in Japan. The hospital BCS-G number is a surrogate
      marker of operative mortality.

PMID- 27688031
TI  - Safety and efficacy of an "enhanced recovery after surgery" protocol for patients
      undergoing colon cancer surgery: a multi-institutional controlled study.
AB  - PURPOSE: The aim of this multi-institutional study was to prospectively evaluate
      the safety and efficacy of an enhanced recovery after surgery (ERAS) protocol for
      colonic surgery. METHODS: The subjects of this study were 320 patients with an
      American Society of Anesthesiologists (ASA) grade I or II physical status.
      Patients underwent elective open or laparoscopic colonic resection or high
      anterior resection between April 2011 and January 2014 at one of six
      institutions. Three hospitals implemented an ERAS protocol (n = 159), and three
      administered conventional care (n = 161). The primary outcome measure was the
      surgical complication rate. RESULTS: Most operations, irrespective of group, were
      performed laparoscopically. The incidence of a surgical complication was 17.0 %
      in the ERAS group vs. 16.1 % in the conventional group (P = 0.842), in which
      several non-surgical complications also arose. Oral food intake was implemented
      earlier for the ERAS group vs. the conventional group, after a median (range) of
      1 (1-31) vs. 3 (1-9) days for the ERAS vs. conventional care groups, respectively
      (P < 0.001). The median length of postoperative hospital stay was reduced by 5.5
      days for the ERAS group, being 8.5 (5-41) vs. 14 (7-56) days for the ERAS vs.
      conventional care groups, respectively (P < 0.001). CONCLUSION: This multi
      institutional controlled study clearly demonstrated that an ERAS protocol was
      efficient, without increasing the complication risk.

PMID- 27688032
TI  - Treatment of simultaneously discovered lung cancer and cardiovascular disease: a
      20-year single-institution experience.
AB  - PURPOSE: To propose a treatment strategy for simultaneously discovered non-small
      cell lung cancer (NSCLC) and cardiovascular disease (CVD). METHODS: Of 1302
      patients who underwent surgery for NSCLC, CVD requiring invasive treatment was
      simultaneously discovered in 33 (3 %). The details of the treatments as well as
      the short- and long-term outcomes of pulmonary resection were analyzed. RESULTS:
      CVD included coronary artery disease in 20 patients, valvular disease in 6,
      abdominal aortic aneurysm in 5, and congenital heart disease in 2. Twenty-six
      patients underwent two-stage treatment, while seven received simultaneous
      surgery. In 23 patients whose treatment for CVD preceded that for lung cancer,
      the median interval between those treatments was 78 days (range 18-197 days).
      Postoperative complications occurred in 8 (31 %) of 26 patients who underwent 2
      stage treatment and in 3 (43 %) of 7 who underwent simultaneous surgery. Notably,
      of 3 patients who underwent lobectomy or bilobectomy, 2 (67 %) experienced
      respiratory dysfunction that required intubation. The 5-year overall survival
      rate of all 33 patients was 84.5 %. CONCLUSION: The outcomes of two-stage
      treatment in the present cohort were favorable. Given our experience,
      simultaneous surgery for lung cancer and CVD should, therefore, be selected only
      for patients who may benefit from that strategy.

PMID- 27688033
TI  - Cloning, expression, molecular characterization and preliminary studies on
      immunomodulating properties of recombinant Trypanosoma congolense calreticulin.
AB  - Trypanosomes are bloodstream protozoan parasites, which are pathogens of
      veterinary and medical importance. Several mammalian species, including humans,
      can be infected by different species of the genus Trypanosoma (T. congolense, T.
      evansi, T. brucei, T. vivax) exhibiting more or less virulent and pathogenic
      phenotypes. A previous screening of the excreted-secreted proteins of T.
      congolense demonstrated an overexpression of several proteins correlated with the
      virulence and pathogenicity of the strain. Of these proteins, calreticulin (CRT)
      has shown differential expression between two T. congolense strains with opposite
      infectious behavior and has been selected as a target molecule based on its
      immune potential functions in parasitic diseases. In this study, we set out to
      determine the role of T. congolense calreticulin as an immune target.
      Immunization of mice with recombinant T. congolense calreticulin induced antibody
      production, which was associated with delayed parasitemia and increased survival
      of the challenged animal. These results strongly suggest that some excreted
      secreted proteins of T. congolense are a worthwhile target candidate to interfere
      with the infectious process.

PMID- 27688034
TI  - Baseline Motivation Type as a Predictor of Dropout in a Healthy Eating Text
      Messaging Program.
AB  - BACKGROUND: Growing evidence suggests that text messaging programs are effective
      in facilitating health behavior change. However, high dropout rates limit the
      potential effectiveness of these programs. OBJECTIVE: This paper describes
      patterns of early dropout in the HealthyYou text (HYTxt) program, with a focus on
      the impact of baseline motivation quality on dropout, as characterized by Self
      Determination Theory (SDT). METHODS: This analysis included 193 users of HYTxt, a
      diet and physical activity text messaging intervention developed by the US
      National Cancer Institute. Descriptive statistics were computed, and logistic
      regression models were run to examine the association between baseline motivation
      type and early program dropout. RESULTS: Overall, 43.0% (83/193) of users dropped
      out of the program; of these, 65.1% (54/83; 28.0% of all users) did so within the
      first 2 weeks. Users with higher autonomous motivation had significantly lower
      odds of dropping out within the first 2 weeks. A one unit increase in autonomous
      motivation was associated with lower odds (odds ratio 0.44, 95% CI 0.24-0.81) of
      early dropout, which persisted after adjusting for level of controlled
      motivation. CONCLUSIONS: Applying SDT-based strategies to enhance autonomous
      motivation might reduce early dropout rates, which can improve program exposure
      and effectiveness.

PMID- 27688035
TI  - Current status of laparoscopic pancreaticoduodenectomy and pancreatectomy.
AB  - This review describes the recent advances in, and current status of, minimally
      invasive pancreatic surgery (MIPS). Typical MIPS procedures are laparoscopic
      pancreaticoduodenectomy (LPD), laparoscopic distal pancreatectomy (LDP),
      laparoscopic central pancreatectomy (LCP), and laparoscopic total pancreatectomy
      (LTP). Some retrospective studies comparing LPD or LDP and open procedures have
      demonstrated the safety and feasibility as well as the intraoperative outcomes
      and postoperative recovery of these procedures. In contrast, LCP and LTP have not
      been widely accepted as common laparoscopic procedures owing to their complicated
      reconstruction and limited indications. Nevertheless, our concise review reveals
      that LCP and LTP performed by expert laparoscopic surgeons can result in good
      short-term and long-term outcomes. Moreover, as surgeons' experience with
      laparoscopic techniques continues to grow around the world, new innovations and
      breakthroughs in MIPS will evolve. Well-designed and suitably powered randomized
      controlled trials of LPD, LDP, LCP, and LTP are now warranted to demonstrate the
      superiority of these procedures.

PMID- 27688037
TI  - Hydrodisplacement of sural nerve for safety and efficacy of endovenous thermal
      ablation for small saphenous vein incompetence.
AB  - Background Endovenous radio frequency ablation for small saphenous vein
      incompetence by and large appears to be superior and safer than conventional open
      surgery. Small saphenous vein ablation from approximately mid-calf to the point
      proximally where the small saphenous vein dives into the popliteal fossa is
      considered to be safe, as the sural nerve is in most cases separated from this
      segment of the small saphenous vein by the deep fascia. The outcome of the distal
      incompetent small saphenous vein remains unclear. Efficacy of the endovenous
      radio frequency ablation can be enhanced by increasing the length of the
      ablatable small saphenous vein segment. Methodology To optimise endovenous radio
      frequency ablation outcome, the distal small saphenous vein may be made amenable
      to ablation if safety of the sural nerve can be assured. The sural nerve was
      successfully located using duplex ultrasound in 100% of our cohort in this study.
      The standard entry point for venous access was just above the lateral malleolus.
      After introduction of the introducer sheath, the radio frequency catheter was
      advanced proximally; the sural nerve was displaced from the small saphenous vein
      by approximately 1 cm with the administration of tumescent anaesthesia (
      hydrodisplacement). A total of 118 patients underwent extended endovenous radio
      frequency ablation of 124 incompetent small saphenous vein trunks using the
      method described. Results Successful extended ablation of the small saphenous
      vein was achieved in 100% of cases and it was confirmed by duplex scanning at one
      and six weeks. Two neurological events were recorded during the study:  1. One
      patient with temporary foot drop lasting for less than 6 h with complete
      recovery.  2. A second patient with a sural nerve sensory deficit reported by the
      patient at day 2-3, which remains current at six weeks. Conclusions Extended
      endovenous radio frequency ablation of the small saphenous vein to optimise
      length of the ablatable vein segment is feasible with careful identification and
      hydrodisplacement of the sural nerve. This method is shown to be associated with
      fewer neurological complications than other methods reported in the literature.

PMID- 27688036
TI  - Effects of an endothelin receptor antagonist, Macitentan, on right ventricular
      substrate utilization and function in a Sugen 5416/hypoxia rat model of severe
      pulmonary arterial hypertension.
AB  - BACKGROUND: Altered myocardial energy metabolism has been linked to worsening of
      RV function in pulmonary arterial hypertension (PAH). The aim of this study was
      to evaluate RV glucose and fatty acid metabolism in vivo in a rat model of PAH
      using positron emission tomography (PET) and investigate the effects of
      Macitentan on RV substrate utilization. METHODS: PAH was induced in male Sprague
      Dawley rats by a single subcutaneous injection of Sugen 5416 (20 mg/kg) followed
      by 3 weeks of hypoxia (10% oxygen). At week 5 post-injection, the PAH rats were
      randomized to Macitentan (30 mg/kg daily) treatment or no treatment. Substrate
      utilization was serially assessed 5 and 8 weeks post-injection with 2-[18F]fluoro
      2-deoxyglucose (FDG) and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) PET
      for glucose and fatty acid metabolism respectively and correlated with in vivo
      functional measurements. RESULTS: PAH induction resulted in a 2.5-fold increase
      in RV FDG uptake (standardized uptake value (SUV) of normal control: 1.6 +/- 0.4,
      week 5: 4.1 +/- 1.9, week 8: 4.0 +/- 1.6, P < 0.05 for all groups vs. control).
      RV FTHA showed twofold increased uptake at week 5 (SUV control: 1.50 +/- 0.39,
      week 5: 3.06 +/- 1.10, P = 0.03). Macitentan significantly decreased RV FDG
      uptake at 8 weeks (SUV: 2.5 +/- 0.9, P = 0.04), associated with improved RV
      ejection fraction and reduced RV systolic pressure, while FTHA uptake was
      maintained. CONCLUSION: PAH is associated with metabolic changes in the RV,
      characterized by a marked increase in FDG and FTHA uptake. Macitentan treatment
      reduced PAH severity and was associated with a decrease in RV FDG uptake and
      improved RV function.

PMID- 27688038
TI  - Angiomatosis of soft tissue as an important differential diagnosis for
      intramuscular venous malformations.
AB  - Background We aimed to improve management of extremity low-flow vascular
      malformations by analyzing the histology and imaging of venous malformations
      (VMs) not responsive to sclerotherapy. Method We reviewed patient records of 102
      consecutive patients treated with sclerotherapy for extremity VM in our
      institution to identify patients who had undergone surgery due to insufficient
      response. We semi-quantitatively analysed the tissue specimens and compared
      histological findings to those in preoperative imaging. Result The number of
      patients operated on was 19 (18.6%); 15 of them had lower-extremity intramuscular
      lesions. The histological pattern of 13 of these 15 lesions corresponded to
      angiomatosis of soft tissue (AST). All other lesions treated surgically were VMs.
      The histology of AST was distinctive but magnetic resonance imaging findings
      often overlapped with those of VM. Conclusion AST is easily mixed with
      intramuscular VM. The differentiation of these two entities has therapeutic
      importance. We emphasize the role of histology in the differential diagnostics of
      intramuscular slow-flow vascular malformations.

PMID- 27688039
TI  - Colluvium supply in humid regions limits the frequency of storm-triggered
      landslides.
AB  - Shallow landslides, triggered by extreme rainfall, are a significant hazard in
      mountainous landscapes. The hazard posed by shallow landslides depends on the
      availability and strength of colluvial material in landslide source areas and the
      frequency and intensity of extreme rainfall events. Here we investigate how the
      time taken to accumulate colluvium affects landslide triggering rate in the
      Southern Appalachian Mountains, USA and how this may affect future landslide
      hazards. We calculated the failure potential of 283 hollows by comparing
      colluvium depths to the minimum (critical) soil depth required for landslide
      initiation in each hollow. Our data show that most hollow soil depths are close
      to their critical depth, with 62% of hollows having soils that are too thin to
      fail. Our results, supported by numerical modeling, reveal that landslide
      frequency in many humid landscapes may be insensitive to projected changes in the
      frequency of intense rainfall events.

PMID- 27688040
TI  - Role of NF-kbeta factor Rel2 during Plasmodium falciparum and bacterial infection
      in Anopheles dirus.
AB  - BACKGROUND: Anopheles mosquitoes transmit malaria which is one of the world's
      most threatening diseases. Anopheles dirus (sensu stricto) is among the main
      vectors of malaria in South East Asia. The mosquito innate immune response is the
      first line of defence against malaria parasites during its development. The
      immune deficiency (IMD) pathway, a conserved immune signaling pathway, influences
      anti-Plasmodium falciparum activity in Anopheles gambiae, An. stephensi and An.
      albimanus. The aim of the study was to determine the role of Rel2, an IMD pathway
      controlled NF-kappabeta transcription factor, in An. dirus. METHODS: RACE (Rapid
      amplification of cDNA ends) was performed on the Rel2 gene. Double-stranded Rel2
      was constructed and injected into the thorax of female mosquitoes. The injected
      mosquitoes were fed on a P. falciparum gametocyte culture and dissected on day 7
      9 post-feeding in order to count the oocysts. A survival analysis was conducted
      by exposing the dsRNA injected mosquitoes to Gram-positive and Gram-negative
      bacteria. RESULTS: This study demonstrated that the Rel2 gene in An. dirus has
      two isoforms, short length and full length. RNA interference-mediated gene
      silencing of Rel2 showed that the latter is involved in protection against P.
      falciparum, Gram-positive bacteria (Micrococcus luteus) with Lys-type
      peptidoglycan and Gram-negative bacteria (Escherichia coli) with DAP-type
      peptidoglycan. CONCLUSION: This study suggested that there are similarities in
      the splicing events and functionality of the Rel2 gene, between the Anopheles
      species. Among all the important anophelines, the immunity of only a few has been
      thoroughly investigated. In order to develop novel vector-based control
      strategies and restrict malaria transmission, the immune pathways of these
      important vectors should be thoroughly investigated.

PMID- 27688041
TI  - Orphan nuclear receptor SHP regulates iron metabolism through inhibition of BMP6
      mediated hepcidin expression.
AB  - Small heterodimer partner (SHP) is a transcriptional corepressor regulating
      diverse metabolic processes. Here, we show that SHP acts as an intrinsic negative
      regulator of iron homeostasis. SHP-deficient mice maintained on a high-iron diet
      showed increased serum hepcidin levels, decreased expression of the iron exporter
      ferroportin as well as iron accumulation compared to WT mice. Conversely,
      overexpression of either SHP or AMP-activated protein kinase (AMPK), a metabolic
      sensor inducing SHP expression, suppressed BMP6-induced hepcidin expression. In
      addition, an inhibitory effect of AMPK activators metformin and AICAR on BMP6
      mediated hepcidin gene expression was significantly attenuated by ablation of SHP
      expression. Interestingly, SHP physically interacted with SMAD1 and suppressed
      BMP6-mediated recruitment of the SMAD complex to the hepcidin gene promoter by
      inhibiting the formation of SMAD1 and SMAD4 complex. Finally, overexpression of
      SHP and metformin treatment of BMP6 stimulated mice substantially restored
      hepcidin expression and serum iron to baseline levels. These results reveal a
      previously unrecognized role for SHP in the transcriptional control of iron
      homeostasis.

PMID- 27688042
TI  - Proton Conducting Graphene Oxide/Chitosan Composite Electrolytes as Gate
      Dielectrics for New-Concept Devices.
AB  - New-concept devices featuring the characteristics of ultralow operation voltages
      and low fabrication cost have received increasing attention recently because they
      can supplement traditional Si-based electronics. Also, organic/inorganic
      composite systems can offer an attractive strategy to combine the merits of
      organic and inorganic materials into promising electronic devices. In this
      report, solution-processed graphene oxide/chitosan composite film was found to be
      an excellent proton conducting electrolyte with a high specific capacitance of
      ~3.2 MUF/cm2 at 1.0 Hz, and it was used to fabricate multi-gate electric double
      layer transistors. Dual-gate AND logic operation and two-terminal diode operation
      were realized in a single device. A two-terminal synaptic device was proposed,
      and some important synaptic behaviors were emulated, which is interesting for
      neuromorphic systems.

PMID- 27688044
TI  - Diabetes: Blood pressure goals in T2DM - time for a rethink?

PMID- 27688045
TI  - Metabolic effects of smoking cessation.

PMID- 27688043
TI  - Evaluation of medicine retail outlets for sale of typhoid fever vaccine among
      adults in two urban and rural settings in western Kenya: a proof-of-concept
      study.
AB  - BACKGROUND: Private sector medicine outlets are an important provider of health
      services across the developing world, and are an untapped means of distributing
      and selling vaccines outside of childhood immunization programs. The present
      study assessed the viability of medicine outlets (chemists and pharmacies) as
      potential channels for sale of vaccines. METHODS: To evaluate the viability of
      the medicine outlet model, we partnered with nine outlets across urban and rural
      communities in western Kenya to sell a nurse-administered typhoid vaccine.
      Purchasers were surveyed to reveal market demographic characteristics, reasons
      for vaccine purchase, and sources of information about the program. Key informant
      interviews and focus group discussions defined acceptability, demand, and
      additional suggestions for improving this mechanism of selling and distributing
      vaccines. RESULTS: There was a higher than expected demand for the vaccine that
      resulted in stock-outs. Previous instance of typhoid, desire to prevent disease,
      affordable price and convenience were cited by most participants as main reasons
      for purchase of vaccine at the local outlet. The most common source of
      information on the vaccine sale was word-of-mouth and referral from friends.
      Longer vaccine sale duration, adequate stocking of vaccines and extended hours of
      administration in the evening to allow working individuals to buy vaccines were
      cited by participants as ways for improved participation in the future.
      CONCLUSIONS: This study demonstrated a high demand for vaccines at community
      medicine outlets. Important insights on how to improve and sustain such a program
      included extension of distribution time, education of outlet keepers, and
      minimizing vaccine stockouts. With improved social marketing, infrastructure
      mapping, education and pricing schemes, medicine outlets could become a
      sustainable avenue for selling adult vaccines in emerging markets for both
      routine and pandemic vaccines.

PMID- 27688046
TI  - Pituitary disease: Inflammation in patients with Cushing disease.

PMID- 27688047
TI  - Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of
      Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.
AB  - Treatment of patients with multiple brain metastases using a single-isocenter
      volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time
      with the tradeoff of larger low dose to the normal brain tissue. We have
      developed an efficient Projection Summing Optimization Algorithm to optimize the
      treatment geometry in order to reduce dose to normal brain tissue for
      radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm:
      (a) measures coordinates of outer boundary points of each lesion to be treated
      using the Eclipse Scripting Application Programming Interface, (b) determines the
      rotations of couch, collimator, and gantry using three matrices about the
      cardinal axes, (c) projects the outer boundary points of the lesion on to Beam
      Eye View projection plane, (d) optimizes couch and collimator angles by selecting
      the least total unblocked area for each specific treatment arc, and (e) generates
      a treatment plan with the optimized angles. The results showed significant
      reduction in the mean dose and low dose volume to normal brain, while maintaining
      the similar treatment plan qualities on the thirteen patients treated previously.
      The algorithm has the flexibility with regard to the beam arrangements and can be
      integrated in the treatment planning system for clinical application directly.

PMID- 27688048
TI  - Advance care planning: outpatient antenatal palliative care consultation.

PMID- 27688049
TI  - Are proton pump inhibitors a threat for spontaneous bacterial peritonitis and
      hepatic encephalopathy in cirrhosis? Not so fast.

PMID- 27688050
TI  - Feel the heat: activation, orientation and feeding responses of bed bugs to
      targets at different temperatures.
AB  - Host location in bed bugs is poorly understood. Of the primary host-associated
      cues known to attract bed bugs - CO2, odors, heat - heat has received little
      attention as an independent stimulus. We evaluated the effects of target
      temperatures ranging from 23 to 48 degrees C on bed bug activation, orientation
      and feeding. Activation and orientation responses were assessed using a heated
      target in a circular arena. All targets heated above ambient temperature
      activated bed bugs (initiated movement) and elicited oriented movement toward the
      target, with higher temperatures generally resulting in faster activation and
      orientation. The distance over which bed bugs could orient toward a heat source
      was measured using a 2-choice T-maze assay. Positive thermotaxis was limited to
      distances <3 cm. Bed bug feeding responses on an artificial feeding system
      increased with feeder temperature up to 38 and 43 degrees C, and declined
      precipitously at 48 degrees C. In addition, bed bugs responded to the relative
      difference between ambient and feeder temperatures. These results highlight the
      wide range of temperatures that elicit activation, orientation and feeding
      responses in bed bugs. In contrast, the ability of bed bugs to correctly orient
      towards a heated target, independently of other cues, is limited to very short
      distances (<3 cm). Finally, bed bug feeding is shown to be relative to ambient
      temperature, not an absolute response to feeder blood temperature.

PMID- 27688051
TI  - Asymmetric energetic costs in reciprocal-cross hybrids between carnivorous mice
      (Onychomys).
AB  - Aerobic respiration is a fundamental physiological trait dependent on coordinated
      interactions between gene products of the mitochondrial and nuclear genomes.
      Mitonuclear mismatch in interspecific hybrids may contribute to reproductive
      isolation by inducing reduced viability (or even complete inviability) due to
      increased metabolic costs. However, few studies have tested for effects of
      mitonuclear mismatch on respiration at the whole-organism level. We explored how
      hybridization affects metabolic rate in closely related species of grasshopper
      mice (genus Onychomys) to better understand the role of metabolic costs in
      reproductive isolation. We measured metabolic rate across a range of temperatures
      to calculate basal metabolic rate (BMR) and cold-induced metabolic rate (MRc) in
      O. leucogaster, O. torridus and O. arenicola, and in reciprocal F1 hybrids
      between the latter two species. Within the genus, we found a negative correlation
      between mass-specific BMR and body mass. Although O. arenicola was smaller than
      O. torridus, hybrids from both directions of the cross resembled O. arenicola in
      body mass. In contrast, hybrid BMR was strongly influenced by the direction of
      the cross: reciprocal F1 hybrids were different from each other but
      indistinguishable from the maternal species. In addition, MRc was not
      significantly different between hybrids and either parental species. These
      patterns indicate that metabolic costs are not increased in Onychomys F1 hybrids
      and, while exposure of incompatibilities in F2 hybrids cannot be ruled out,
      suggest that mitonuclear mismatch does not act as a primary barrier to gene flow.
      Maternal matching of BMR is suggestive of a strong effect of mitochondrial
      genotype on metabolism in hybrids. Together, our findings provide insight into
      the metabolic consequences of hybridization, a topic that is understudied in
      mammals.

PMID- 27688052
TI  - Speed-dependent interplay between local pattern-generating activity and sensory
      signals during walking in Drosophila.
AB  - In insects, the coordinated motor output required for walking is based on the
      interaction between local pattern-generating networks providing basic rhythmicity
      and leg sensory signals, which modulate this output on a cycle-to-cycle basis.
      How this interplay changes speed-dependently and thereby gives rise to the
      different coordination patterns observed at different speeds is not sufficiently
      understood. Here, we used amputation to reduce sensory signals in single legs and
      decouple them mechanically during walking in Drosophila. This allowed for the
      dissociation between locally generated motor output in the stump and coordinating
      influences from intact legs. Leg stumps were still rhythmically active during
      walking. Although the oscillatory frequency in intact legs was dependent on
      walking speed, stumps showed a high and relatively constant oscillation frequency
      at all walking speeds. At low walking speeds we found no strict cycle-to-cycle
      coupling between stumps and intact legs. In contrast, at high walking speeds
      stump oscillations were strongly coupled to the movement of intact legs on a one
      to-one basis. Although during slow walking there was no preferred phase between
      stumps and intact legs, we nevertheless found a preferred time interval between
      touch-down or lift-off events in intact legs and levation or depression of
      stumps. Based on these findings, we hypothesize that, as in other insects,
      walking speed in Drosophila is predominantly controlled by indirect mechanisms
      and that direct modulation of basic pattern-generating circuits plays a
      subsidiary role. Furthermore, inter-leg coordination strength seems to be speed
      dependent and greater coordination is evident at higher walking speeds.

PMID- 27688053
TI  - Unique magnetostriction of Fe68.8Pd31.2 attributable to twinning.
AB  - Fe68.8Pd31.2 exhibits an anomalously large magnetostriction of ~400 ppm at room
      temperature as well as linear, isotropic, and hysteresis free magnetization
      behavior. This near perfectly reversible magnetic response is attributable to the
      presence of a large number of premartensitic magnetoelastic twin clusters present
      in the system made possible through the elastic softening that occurs near a
      martensitic transformation temperature of 252 K. It is proposed that the twin
      clusters in the material reduce both internal elastic and magnetic energy,
      causing the elastic and magnetic behavior of the material to be intimately
      linked. In such a framework, the anisotropy energy becomes extremely low causing
      the material to bear no crystalline dependence on magnetization, and application
      of a magnetic field causes simultaneous magnetic and twin domain movement which
      relaxes the system.

PMID- 27688054
TI  - Detecting reproductive system abnormalities of broiler breeder roosters at
      different ages.
AB  - The objective of this study was to detect the reasons of rooster's fertility
      decrease at 50 weeks of age. Therefore, the reproductive system of broiler
      breeder roosters was laparoscopic, macroscopic and histopathology evaluated, and
      a comparison of the anatomical aspect with the sperm analysis and birds' age was
      realized. Cobb roosters (n = 59) were distributed into two groups (30 and 50
      weeks). Evaluations were performed with laparoscopy, macroscopy and
      histopathology, and seminal quality, blood serum testosterone concentration and
      weight were also determined. The old roosters presented smaller testicle size,
      higher intensity epididymal lithiasis and lower testicle sperm production,
      compared to the young roosters. The use of the endoscope could easily distinguish
      a normal-sized testicle than an atrophic one. Four old roosters with severe
      testicular atrophy did not show spermatogenesis, although three still had sperm
      in the ejaculate. This would falsely indicate a wrong diagnosis of normal
      fertility before the testicular atrophy took place. In conclusion, in addition to
      the weight increase with age, the testicular atrophy and impairment of sperm
      production seemed to be the main reason to the decrease in the rooster's
      fertility at 50 weeks of age. Therefore, the use of the laparoscopy as a way to
      detect the roosters with testicular atrophy before 50 weeks of age and their
      removal from them flock could be useful as a diagnostic tool to prevent the
      birds' fertility loss.

PMID- 27688055
TI  - Proteomic analysis of pear (Pyrus pyrifolia) ripening process provides new
      evidence for the sugar/acid metabolism difference between core and mesocarp.
AB  - Pears are one of the most popular nutrient-rich fruits in the world. The pear
      core and mesocarp have significantly different metabolism, although they display
      similar profiles. Most strikingly, the core is more acidic in taste. Our results
      showed that there is more titrated acid but lower total soluble solids in the
      core compared to the mesocarp, and the content of citric acid was more than 17
      fold higher in the core compared to the mesocarp at the ripening stage.
      Proteomics was used to investigate the difference between core and mesocarp
      tissues during "Cuiguan" pear ripening. Fifty-four different protein expression
      patterns were identified in the core and mesocarp. In general, common variably
      expressed proteins between the core and mesocarp were associated with important
      physiological processes, such as glycolysis, pyruvate metabolic processes, and
      oxidative stress. Further, protein level associated qRT-PCR verification revealed
      a higher abundance of fructose-bisphosphate aldolase and NADP-dependent malic
      enzymes, which may play a role in the low acid content in the mesocarp, whereas a
      higher abundance of disulfide isomerase-like 2-2 and calcium-dependent lipid
      binding in the core may explain why it is less prone to accumulate sugar. The
      different levels of a few typical ROS scavenger enzymes suggested that oxidative
      stress is higher in the core than in the mesocarp. This study provides the first
      characterization of the pear core proteome and a description of its variation
      compared to the mesocarp during ripening.

PMID- 27688056
TI  - Health game interventions to enhance physical activity self-efficacy of children:
      a quantitative systematic review.
AB  - AIM: To describe and explore health game interventions that enhance the physical
      activity self-efficacy of children and to evaluate the effectiveness of these
      interventions. BACKGROUND: Physical inactivity among children has increased
      globally. Self-efficacy is one of the key determinants of physical activity
      engagement in children. There is a need to explore new and innovative
      interventions to enhance physical activity self-efficacy that are also acceptable
      for today's children. DESIGN: Quantitative systematic review. DATA SOURCES:
      MEDLINE (Ovid), CINAHL, PsychInfo, EMBASE and the Cochrane Library between 1996
      2016. REVIEW METHODS: A review was conducted in accordance with the Cochrane
      Collaboration guidelines. A systematic search was done in June 2016 by two
      independent reviewers according to the eligibility criteria as follows:
      controlled trial, comparison of digital game intervention with no game
      intervention control condition, participants younger than 18 years of age and
      reported statistical analyses of a physical activity self-efficacy outcome
      measure. RESULTS: Altogether, five studies met the eligibility criteria. Four
      game interventions, employing three active games and one educational game, had
      positive effects on children's physical activity self-efficacy. An intervention,
      employing a game-themed mobile application, showed no intervention effects. The
      variation between intervention characteristics was significant and the quality of
      the studies was found to be at a medium level. CONCLUSION: Although health game
      interventions seemingly enhance the physical activity self-efficacy of children
      and have potential as a means of increasing physical activity, more rigorous
      research is needed to clarify how effective such interventions are in the longer
      run to contribute to the development of game-based interventions.

PMID- 27688058
TI  - Current insights into the sulfatase pathway in human testis and cultured Sertoli
      cells.
AB  - Within the human testis, large amounts of sulfated steroid hormones are produced.
      As shown in breast tissue and placenta, these might not only be excretion
      intermediates, but re-activated in target cells by steroid sulfatase (STS). This
      process is called sulfatase pathway and may play a pivotal role in para- and/or
      intracrine regulation by creating a local supply for steroid hormones. This
      requires a facilitated transport via uptake carriers and efflux transporters as
      these hydrophilic molecules cannot pass the cell membrane. Moreover, blood-testis
      barrier formation in the testis requires a transport through Sertoli cells (SCs)
      to reach germ cells (GCs). Sertoli cells are therefore expected to play a key
      role as gate-keepers for sulfatase pathway in human seminiferous epithelium. We
      analyzed the mRNA and protein expression of uptake carriers and efflux
      transporters like organic anion-transporting polypeptides (OATP2B1, OATP3A1) and
      multidrug resistance-related proteins (MRP1, MRP4) in testicular tissue and
      cultured Sertoli cells (FS1, HSEC). Additionally, expression pattern of STS as
      well as sulfonating enzymes (SULTs) were assessed. OATP2B1, OATP3A1 and STS were
      detected in SCs as well as GCs, whereas MRP1 is only expressed in SCs, and
      SULT1E1 only in Leydig cells, respectively. By transcellular transport of
      [H3]DHEAS in HSEC, we showed a functional transport of sulfated steroids in
      vitro. Our data indicate that steroid synthesis via sulfatase pathway in Sertoli
      cells in vivo and in vitro is possible and may contribute to paracrine and
      intracrine regulation employing the local supply of sulfated and free steroid
      hormones inside seminiferous tubules.

PMID- 27688059
TI  - Primary cardiac hydatid cyst presenting as noncompaction cardiomyopathy.
AB  - We report a case of cyst was initially labeled as left ventricular noncompaction
      cardiomyopathy. An accurate diagnosis is essential to establish the most
      effective treatment strategy. In particular, echocardiographic examination
      assists in identifying the correct diagnosis. In this case, two-dimensional and
      three-dimensional echocardiography and computed tomography were used for
      definitive diagnosis of cardiac hydatid cyst.

PMID- 27688060
TI  - The northern exposure sign.

PMID- 27688057
TI  - Using electron microscopes to look into the lung.
AB  - In the nineteenth century, there was a dispute about the existence of a lung
      alveolar epithelium which remained unsolved until the invention of electron
      microscopy (EM) and its application to the lung. From the early 1960s, Ewald
      Weibel became the master of lung EM. He showed that the alveolar epithelium is
      covered with a lining layer containing surfactant. Weibel also explained the
      phenomenon of "non-nucleated plates" observed already in 1881 by Albert Kolliker.
      Weibel's most significant contribution was to the development of stereological
      methods. Therefore, quantitative characterization of lung structure revealing
      structure-function relationships became possible. Today, the spectrum of EM
      methods to study the fine structure of the lung has been extended significantly.
      Cryo-preparation techniques are available which are necessary for immunogold
      labeling of molecules. Energy-filtering techniques can be used for the detection
      of elements. There have also been major improvements in stereology, thus
      providing a very versatile toolbox for quantitative lung phenotype analyses. A
      new dimension was added by 3D EM techniques. Depending on the desired sample size
      and resolution, the spectrum ranges from array tomography via serial block face
      scanning EM and focused ion beam scanning EM to electron tomography. These 3D
      datasets provide new insights into lung ultrastructure. Biomedical EM is an ever
      developing field. Its high resolution remains unparalleled. Moreover, EM has the
      unique advantage of providing an "open view" into cells and tissues within their
      full architectural context. Therefore, EM will remain an indispensable tool for a
      better understanding of the lung's functional design.

PMID- 27688062
TI  - The spaghetti sign.

PMID- 27688061
TI  - Microwave ablation for hepatocellular carcinoma associated with Budd-Chiari
      syndrome after transarterial chemoembolization: an analysis of ten cases.
AB  - PURPOSE: To evaluate the feasibility, efficacy, and safety of microwave ablation
      (MWA) in the treatment of hepatocellular carcinoma associated with Budd-Chiari
      syndrome (BCS) after transarterial chemoembolization (TACE). METHODS: A total of
      10 patients (mean 50.0 +/- 7.5 years) with 15 BCS-associated HCC lesions were
      retrospectively evaluated. All patients received MWA treatment for residual
      tumors after 1 to 3 sessions of TACE. The diagnosis of residual tumors was
      confirmed by at least two types of enhanced imaging. CEUS images were performed
      to confirm the residual lesions and guide the placement of antenna before MWA.
      Thermal monitoring and artificial pleural effusion or ascites were used to
      guarantee ablative accuracy and safety for patients with tumors adjacent to vital
      structures. Technical success, technique efficacy, local tumor progression,
      survival rate, and the incidence of complications were comprehensively analyzed.
      RESULTS: Technical success and technique effectiveness were achieved in all
      patients. Thirteen lesions achieved complete ablation for the first time, and 2
      lesions needed two sessions. Thermal monitoring was used in 2 patients,
      artificial pleural effusion was used in 1 patient, and artificial ascites in 2
      patients. In a median follow-up of 34.5 months (range 21-52 months), no LTP was
      founded in all patients. Intrahepatic recurrence was found in 5 patients. 1-, 2-,
      3-, and 4-year survival rates were 100%, 100%, 74.1%, and 37.0%, respectively. No
      major or minor complications were observed. CONCLUSION: Microwave ablation is a
      feasible and effective way to treat residual tumors after TACE treatment in
      patients with BCS-associated HCC.

PMID- 27688065
TI  - Editorial Comment from Dr Kitagawa to Clinicopathological features and outcomes
      in patients with late recurrence of renal cell carcinoma after radical surgery.

PMID- 27688063
TI  - Agreement between region-of-interest- and parametric map-based hepatic proton
      density fat fraction estimation in adults with chronic liver disease.
AB  - PURPOSE: To compare agreement between region-of-interest (ROI)- and parametric
      map-based methods of hepatic proton density fat fraction (PDFF) estimation in
      adults with known or suspected hepatic steatosis secondary to chronic liver
      disease over a range of imaging and analysis conditions. MATERIALS AND METHODS:
      In this IRB approved HIPAA compliant prospective single-site study, 31 adults
      with chronic liver disease undergoing clinical gadoxetic acid-enhanced liver
      magnetic resonance imaging at 3 T were recruited. Multi-echo gradient-echo
      imaging at flip angles of 10 degrees  and 50 degrees  was performed before and
      after administration of gadoxetic acid. Six echoes were acquired at successive
      nominally out-of-phase and in-phase echo times. PDFF was estimated with a
      nonlinear fitting algorithm using the first two, three, four, five, and (all) six
      echoes. Hence, 20 different imaging and analysis conditions were used (pre/post
      contrast x low/high flip angle x 2/3/4/5/6 echoes). For each condition, PDFF
      estimation was done in corresponding liver locations using two methods: a region
      of-interest (ROI)-based method in which mean signal intensity values within ROIs
      were run through the fitting algorithm, and a parametric map-based method in
      which individual signal intensities were run through the fitting algorithm pixel
      by pixel. Agreement between ROI- and map-based PDFF estimation was assessed by
      Bland-Altman and intraclass correlation (ICC) analysis. RESULTS: Depending on the
      condition and method, PDFF ranged from -2.52% to 45.57%. Over all conditions,
      mean differences between ROI- and map-based PDFF estimates ranged from 0.04% to
      0.24%, with all ICCs >=0.999. CONCLUSION: Agreement between ROI- and parametric
      map-based PDFF estimation is excellent over a wide range of imaging and analysis
      conditions.

PMID- 27688066
TI  - Synthesis of Water Dispersible Fluorescent Carbon Nanocrystals from Syzygium
      cumini Fruits for the Detection of Fe3+ Ion in Water and Biological Samples and
      Imaging of Fusarium avenaceum Cells.
AB  - In this work, water dispersible fluorescent carbon nanocrystals (NCs) were
      synthesized by a simple, green and low cost hydrothermal method using Syzygium
      cumini (jamun) as a carbon source at 180  degrees C for 6 h. The average size of
      carbon NCs was found to be 2.1 +/- 0.5 nm and shown bright blue fluorescence when
      excited at 365 nm under UV lamp. The carbon NCs were characterized by
      spectroscopic (UV-visible and fluorescence, Fourier transform infrared and
      dynamic light scattering) and high resolution transmission electron microscopic
      techniques. The quantum yield of carbon NCs was found to be ~5.9 % at 438 nm
      emission wavelength when excited at 360 nm. It was noticed that none of the metal
      ions quenched the fluorescence intensity of carbon NCs at 438 nm except for Fe3+,
      indicating the formation of Fe3+ ion-carbon NCs complexes. The linear range was
      observed in the concentration range of 0.01-100 MUM with the corresponding
      detection limits of 0.001 MUM, respectively. Furthermore, the carbon NCs were
      used as probes for imaging of fungal (Fusarium avenaceum) cells.

PMID- 27688067
TI  - The prevalence of chronic peri-pouch sepsis in patients treated for antibiotic
      dependent or refractory primary idiopathic pouchitis.
AB  - AIM: Chronic peri-pouch sepsis (CPPS) may be mistaken for antibiotic-dependent or
      refractory primary idiopathic pouchitis (ADRP), but requires different treatment
      such as drainage. The study aimed to identify the prevalence of CPPS in patients
      thought to have ADRP. The secondary aims were to identify any specific features
      on pouchoscopy suggesting CPPS and to determine the results of treatment for
      CPPS. METHOD: The records of patients who had been treated for ADRP between March
      2006 and June 2015 were reviewed retrospectively. Only those with endoscopic
      evidence of pouch inflammation who had also undergone MRI of the pelvis were
      included. The findings on pouchoscopy and the outcome of treatment were
      determined. RESULTS: Sixty-eight patients (43 men, 63%) were identified with
      apparent ADRP between March 2006 and June 2015. MRI of the pelvis showed CPPS in
      26 (38%). In those with CPPS, the inflammation was more often located in the
      upper pouch alone (15%) compared with patients without CPPS (0%) (P = 0.0184).
      Examination under anaesthesia was performed in 13 of those with CPPS. In five a
      collection was identified and drained; symptoms improved in only one (4%).
      Eighteen patients (69%) remained on antibiotics and seven (27%) had a
      defunctioning stoma or underwent pouch excision. CONCLUSION: In patients thought
      to have ADRP, 38% had CPPS on MRI. There was no clinically relevant specific
      feature on pouchoscopy suggestive of CPPS. The possibility of CPPS should be
      considered early in patients with apparent ADRP and pelvic MRI performed. This
      might lead to earlier detection of CPPS and appropriate treatment.

PMID- 27688068
TI  - Static magnetic fields enhance dental pulp stem cell proliferation by activating
      the p38 mitogen-activated protein kinase pathway as its putative mechanism.
AB  - Dental pulp stem cells (DPSCs) can be a potential stem cell resource for clinical
      cell therapy and tissue engineering. However, obtaining a sufficient number of
      DPSCs for repairing defects is still an issue in clinical applications. Static
      magnetic fields (SMFs) enhance the proliferation of several cell types. Whether
      or not SMFs have a positive effect on DPSC proliferation is unknown. Therefore,
      the aim of this study was to investigate the effect of SMFs on DPSC proliferation
      and its possible intracellular mechanism of action. For methodology, isolated
      DPSCs were cultured with a 0.4-T SMF. Anisotropy of the lipid bilayer was
      examined using a fluorescence polarization-depolarization assay. The
      intracellular calcium ions of the SMF-treated cells were analysed using Fura-2
      acetoxymethyl ester labelling. The cytoskeletons of exposed and unexposed control
      cells were labelled with actin fluorescence dyes. Cell viability was checked when
      the tested cells were cultured with inhibitors of ERK, JNK and p38 to discern the
      possible signalling cascade involved in the proliferative effect of the SMF on
      the DPSCs. Our results showed that SMF-treated cells demonstrated a higher
      proliferation rate and anisotropy value. The intracellular calcium ions were
      activated by SMFs. In addition, fluorescence microscopy images demonstrated that
      SMF-treated cells exhibit higher fluorescence intensity of the actin cytoskeletal
      structure. Cell viability and real-time polymerase chain reaction suggested that
      the p38 signalling cascade was activated when the DPSCs were exposed to a 0.4-T
      SMF. F-actin intensity tests showed that SB203580-treated cells decreased even
      with SMF exposure. Additionally, the F-/G-actin ratio increased due to slowing of
      the cytoskeleton reorganization by p38 mitogen-activated protein kinase
      inhibition. According to these results, we suggest that a 0.4-T SMF affected the
      cellular membranes of the DPSCs and activated intracellular calcium ions. This
      effect may activate p38 mitogen-activated protein kinase signalling, and thus
      reorganize the cytoskeleton, which contributes to the increased cell
      proliferation of the DPSCs. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27688069
TI  - Second-Trimester Ultrasound as a Tool for Early Detection of Fetal Alcohol
      Spectrum Disorders.
AB  - BACKGROUND: Early detection of fetal alcohol spectrum disorders (FASDs) is
      desirable to allow earlier and more comprehensive interventions to be initiated
      for the mother and infant. We examined prenatal ultrasound as an early method of
      detecting markers of the physical features and neurobehavioral deficits
      characteristic of FASD. METHODS: A longitudinal cohort of pregnant women in
      Ukraine was recruited as part of the Collaborative Initiative on Fetal Alcohol
      Spectrum Disorders. Women were enrolled into a moderately to heavy-alcohol
      exposed group or a low- or no-alcohol exposure group and were followed to
      pregnancy outcome. In the second trimester, a fetal ultrasound was performed to
      measure transverse cerebellar diameter, occipital frontal diameter (OFD), caval
      calvarial distance, frontothalamic distance (FTD), interorbital distance (IOD),
      outer orbital diameter, and orbital diameter (OD). Live born infants received a
      dysmorphological examination and a neurobehavioral evaluation using the Bayley
      Scales of Infant Development. These data were used to classify infants with
      respect to FASD. Comparisons were made on the ultrasound measures between those
      with and without features of FASD, adjusting for gestational age at ultrasound
      and maternal smoking. RESULTS: A total of 233 mother/child dyads were included.
      Children classified as FASD had significantly longer IOD and lower FTD/IOD,
      OFD/IOD, and FTD/OD ratios (p < 0.05). Children with a Bayley score <85 had
      significantly shorter FTD, longer IOD, lower OFD/IOD, and FTD/IOD ratios (p <
      0.05). In general, mean differences were small. Ultrasound variables alone
      predicted <10% of the variance in the FASD outcome. CONCLUSIONS: Some ultrasound
      measurements were associated with FASD, selected facial features of the disorder,
      and lower neurobehavioral scores. However, mean differences were relatively
      small, making it difficult to predict affected children based solely on these
      measures. It may be advantageous to combine these easily obtained ultrasound
      measures with other data to aid in identifying high risk for an FASD outcome.

PMID- 27688070
TI  - A supervised weighted similarity measure for gene expressions using biological
      knowledge.
AB  - A supervised similarity measure for Saccharomyces cerevisiae gene expressions is
      developed which can capture the gene similarity when multiple types of
      experimental conditions like cell cycle, heat shock are available for all the
      genes. The measure is called Weighted Pearson correlation (WPC), where the
      weights are systematically determined for each type of experiment by maximizing
      the positive predictive value for gene pairs having Pearson correlation greater
      than 0.80. The positive predictive value is computed by using the annotation
      information available from yeast GO-Slim process annotations in Saccharomyces
      Genome Database (SGD). Genes are then clustered by k-medoid algorithm using the
      newly computed WPC, and functions of 135 unclassified genes are predicted with a
      p-value cutoff 10-5 using Munich Information for Protein Sequences (MIPS)
      annotations. Out of these genes, functional categories of 55 gene are predicted
      with p-value cutoff greater than 10-10 and reported in this investigation. The
      superiority of WPC as compared to some existing similarity measures like Pearson
      correlation and Euclidean distance is demonstrated using positive predictive
      (PPV) values of gene pairs for different Saccharomyces cerevisiae data sets. The
      related code is available at http://www.sampa.droppages.com/WPC.html.

PMID- 27688071
TI  - Transcriptional regulation analysis of FAM3A gene and its effect on adipocyte
      differentiation.
AB  - FAM3A (family with sequence similarity 3, member A) is regulated by PPARG and
      participates in the metabolism of lipid in liver. However, the transcriptional
      regulation analysis of FAM3A is very little and biological function of FAM3A
      still unclear. In this study, the core promoter region and transcription factor
      binding sites of FAM3A gene were identified and characterized using dual
      luciferase report experiments and electrophoretic mobility shift assays (EMSA).
      The promoter activity of FAM3A was dramatically decreased after the mutation of
      C/EBPbeta binding sites, suggesting that C/EBPbeta is a transcriptional activator
      of FAM3A. Overexpression of FAM3A significantly inhibited the efficiency of
      preadipocytes to differentiate into adipocytes as indicated by Western Blot and
      Oil Red O staining assay. These results suggest that C/EBPbeta plays an important
      role in regulating FAM3A promoter activity and FAM3A inhibits adipocyte
      differentiation.

PMID- 27688072
TI  - Treatment of prostate cancer cells with S-adenosylmethionine leads to genome-wide
      alterations in transcription profiles.
AB  - The hypomethylation of DNA may support tumor progression; however, the mechanism
      underlying this relationship is not clear. Several studies have demonstrated that
      the in vitro application of the methyl donor S-adenosylmethionine (SAM) leads to
      promoter remethylation and the downregulation of proto-oncogene expression in
      cancer cells. It is not clear if this represents a general mechanism of SAM or is
      limited to selected genes. We examined this problem using new bisulfite
      sequencing and transcriptomic technologies. Treatment with SAM caused the
      downregulation of proliferation, migration, and invasion of prostate cancer (PC
      3) cells. RNA sequencing revealed the genome-wide downregulation of genes
      involved in proliferation, migration, invasion, and angiogenesis. Real-time PCR
      of a subset of the genes confirmed these results. Reduced representation
      bisulfite sequencing (RRBS) displayed only minor differential methylation between
      treated cells and controls. In summary, we confirmed the anti-proliferative and
      anti-invasive effects of SAM. Additionally, we observed anti-migratory effects
      and downregulation of genes, especially those related to cancerogenesis. For some
      of the related genes, this is the first reported evidence of an association with
      prostate cancer. However, genome-wide modifications in methylation profiles were
      not observed by RRBS; thus, they are obviously not a major cause of alteration in
      transcription profiles and anti-cancer effects.

PMID- 27688073
TI  - Identification of genes in the hypothalamus-pituitary-gonad axis in the brain of
      Amur sturgeons (Acipenser schrenckii) by comparative transcriptome analysis in
      relation to kisspeptin treatment.
AB  - Kisspeptin plays an important role in the reproduction and onset of puberty in
      vertebrates through stimulation of gonadotropin-releasing hormone (GnRH).
      However, the mechanisms whereby kisspeptin-related genes regulate sexual
      differentiation in teleosts are poorly understood. We aimed to study the
      relationship between the hypothalamus-pituitary-gonad (HPG) axis and sexual
      differentiation in relation to kisspeptin in the sturgeon Acipenser schrenckii.
      We performed comparative transcriptomic analysis of the brains of sturgeons
      treated with KISS1-10 during the gonadal sex-differentiation-sensitive period
      (170-210days post-hatching (dph)) using an Illumina sequencing platform. We also
      analyzed mRNA expression levels of genes in the HPG axis using real-time
      quantitative polymerase chain reaction, and measured estradiol-17beta (E2) and
      testosterone (T) levels in the brain and gonads using radioimmunological methods.
      A total of 75,960 and 74,907 unigenes were produced from Kisspeptin-treated and
      physiological saline-treated fish, respectively, among which 47,891 genes were
      matched to the non-redundant nr database. Potential genes and their functions
      were identified by GO (32,435), KEGG (37,619), and COG analyses (18,502). A total
      of 3169 unigenes were differentially expressed between transcriptomes in KISS1-10
      and saline-injected fish, including 300 up-regulated and 2869 down-regulated
      unigenes. Gene expression levels of KISS1, G protein-coupled receptor-54, GnRH,
      androgen receptor, estrogen receptor, and Cyp19a in the brain and gonad were
      significantly affected by KISS1-10 treatment. KISS1-10 injection also
      significantly increased brain levels of E2 and T, compared with controls. These
      results support important roles for KISS1 in the regulation of the HPG axis, and
      in sex differentiation and reproduction in the Amur sturgeon.

PMID- 27688074
TI  - Differential protection by cell wall components of Lactobacillus amylovorus DSM
      16698Tagainst alterations of membrane barrier and NF-kB activation induced by
      enterotoxigenic F4+ Escherichia coli on intestinal cells.
AB  - BACKGROUND: The role of Lactobacillus cell wall components in the protection
      against pathogen infection in the gut is still largely unexplored. We have
      previously shown that L. amylovorus DSM 16698T is able to reduce the
      enterotoxigenic F4+ Escherichia coli (ETEC) adhesion and prevent the pathogen
      induced membrane barrier disruption through the regulation of IL-10 and IL-8
      expression in intestinal cells. We have also demonstrated that L. amylovorus DSM
      16698T protects host cells through the inhibition of NF-kB signaling. In the
      present study, we investigated the role of L. amylovorus DSM 16698T cell wall
      components in the protection against F4+ETEC infection using the intestinal Caco
      2 cell line. METHODS: Purified cell wall fragments (CWF) from L. amylovorus DSM
      16698T were used either as such (uncoated, U-CWF) or coated with S-layer proteins
      (S-CWF). Differentiated Caco-2/TC7 cells on Transwell filters were infected with
      F4+ETEC, treated with S-CWF or U-CWF, co-treated with S-CWF or U-CWF and F4+ETEC
      for 2.5 h, or pre-treated with S-CWF or U-CWF for 1 h before F4+ETEC addition.
      Tight junction (TJ) and adherens junction (AJ) proteins were analyzed by
      immunofluorescence and Western blot. Membrane permeability was determined by
      phenol red passage. Phosphorylated p65-NF-kB was measured by Western blot.
      RESULTS: We showed that both the pre-treatment with S-CWF and the co- treatment
      of S-CWF with the pathogen protected the cells from F4+ETEC induced TJ and AJ
      injury, increased membrane permeability and activation of NF-kB expression.
      Moreover, the U-CWF pre-treatment, but not the co-treatment with F4+ETEC,
      inhibited membrane damage and prevented NF-kB activation. CONCLUSIONS: The
      results indicate that the various components of L. amylovorus DSM 16698T cell
      wall may counteract the damage caused by F4+ETEC through different mechanisms. S
      layer proteins are essential for maintaining membrane barrier function and for
      mounting an anti-inflammatory response against F4+ETEC infection. U-CWF are not
      able to defend the cells when they are infected with F4+ETEC but may activate
      protective mechanisms before pathogen infection.

PMID- 27688075
TI  - Genome-wide DNA methylation in 1-year-old infants of mothers with major
      depressive disorder.
AB  - A genome-wide methylation study was conducted among a sample of 114 infants (M
      age = 13.2 months, SD = 1.08) of low-income urban women with (n = 73) and without
      (n = 41) major depressive disorder. The Illumina HumanMethylation450 BeadChip
      array with a GenomeStudio Methylation Module and Illumina Custom model were used
      to conduct differential methylation analyses. Using the 5.0 * 10-7 p value, 2,119
      loci were found to be significantly different between infants of depressed and
      nondepressed mothers. Infants of depressed mothers had greater methylation at low
      methylation sites (0%-29%) compared to infants of nondepressed mothers. At high
      levels of methylation (70%-100%), the infants of depressed mothers were
      predominantly hypomethylated. The mean difference in methylation between the
      infants of depressed and infants of nondepressed mothers was 5.23%. Disease by
      biomarker analyses were also conducted using GeneGo MetaCore Software. The
      results indicated significant cancer-related differences in biomarker networks
      such as prostatic neoplasms, ovarian and breast neoplasms, and colonic neoplasms.
      The results of a process networks analysis indicated significant differences in
      process networks associated with neuronal development and central nervous system
      functioning, as well as cardiac development between infants of depressed and
      nondepressed mothers. These findings indicate that early in development, infants
      of mothers with major depressive disorder evince epigenetic differences relative
      to infants of well mothers that suggest risk for later adverse health outcomes.

PMID- 27688076
TI  - Event-triggered reliable Hinfinity filter design for networked systems with
      multiple sensor distortions: A probabilistic partition approach.
AB  - In this paper, the problem of event-triggered reliable Hinfinity filtering for
      networked systems with multiple sensor distortions is investigated. The interval
      of sensor distortion in each channel is partitioned several segments. By
      introducing a set of rand variables, the model of multiple sensor distortions
      with their information of probability distribution in each segment is
      established, which is more general than the one in open results. Furthermore, an
      event-triggered communication scheme is proposed to mitigate the utility of
      limited network bandwidth. Then a unified model with consideration of the event
      triggered communication scheme and the sensor distortion is put forward. Based on
      this model, sufficient conditions of the mean square stability of the filtering
      error system and Hinfinity filter parameters are achieved. Finally, a simulation
      example is exploited to demonstrate the effectiveness of the presented method.

PMID- 27688077
TI  - Reinnervation of rat endometrium in the anterior eye chamber model of
      experimental endometriosis: Old methods for new questions.
AB  - Endometriosis is a benign estrogen-dependent chronic gynecological disease
      characterized by the presence of endometrial-like tissue outside the uterine
      cavity. In both women and experimental endometriotic rats, endometriosis lesions
      endow autonomic and sensory nerves, which are thought to contribute to the
      disease-associated pain. Some evidence indicates that the reinnervation of
      lesions is regulated by factors produced by the endometrial tissue as well as by
      environmental factors from the peritoneum. In this study, we examined the
      reinnervation of the rat endometrial tissue in an ectopic environment different
      from the peritoneum employing the anterior eye chamber model of experimental
      endometriosis. At 3 and 6weeks following transplantation, endometrial grafts
      retained many histological features of the eutopic tissue. Both sympathetic and
      sensory nerves reinnervated endometrial grafts and distributed in the stroma-like
      tissue, around blood vessels and in close proximity to the glands and lining
      epithelium. Sympathetic innervation was more robust than sensory innervation. No
      significant topographical relationship between sympathetic nerves and macrophages
      was observed. These results suggest that the rat endometrium possesses intrinsic
      neuritogenic capacities and can be reinnervated by sympathetic and sensory nerves
      in ectopic sites different from the peritoneum.

PMID- 27688079
TI  - Sarcomatoid Adrenal Carcinoma: Case Report with Contribution to Pathogenesis.
AB  - A tumor in the adrenal region with two metastases in the liver was classified as
      poorly differentiated sarcoma on the base of extensive immunostainings
      (expression of vimentin, desmin, myogenin, and CD31, no expression of inhibin,
      melan A). Four years later in a second examination with molecular methods for a
      study of adrenal sarcomas, this diagnosis must be revised due to the lack of MDM
      2 gene amplification and FKHR translocation which exclude sarcoma. Further
      immunostainings of many other parts of the tumor showed in one area more mature
      tumor tissue expressing synaptophysin, SF-1, and melan A. From these findings we
      classified an adrenal cortical cancer with predominant dedifferentiation into a
      sarcomatoid adrenal carcinoma. The properties of this very rare cancer type are
      presented and discussed.

PMID- 27688078
TI  - DNA vaccine encoding central conserved region of G protein induces Th1
      predominant immune response and protection from RSV infection in mice.
AB  - Human respiratory syncytial virus (RSV) can cause serious infection in the lower
      respiratory tract, especially in infants, young children, the elderly and the
      immunocompromised population worldwide. Previous study demonstrated the
      polypeptide (amino acids 148-198) of RSV attachment (G) glycoprotein,
      corresponding to the central conserved region and encompassing CX3C chemokine
      motif, could induce antibodies and protection from RSV challenge in mice [1,2].
      In this study, we evaluated the immune efficacy of the recombinant DNA vaccine of
      pVAX1/3G148-198 encoding RSV G protein polypeptide. RSV specific serum IgG
      antibodies with neutralizing activity were stimulated following prime-boost
      immunization of pVAX1/3G148-198 intramuscularly, and the ratio of IgG2a/IgG1 was
      4.93, indicating a Th1 biased immune response. After challenged intranasally with
      RSV Long, the vaccinated mice showed both decreased lung RSV titers, pulmonary
      inflammation and body weight loss. The results suggest that pVAX1/3G148-198 DNA
      vaccine may be an effective RSV vaccine candidate, and deserves further
      exploration.

PMID- 27688080
TI  - Reliability of Ki-67 Determination in FNA Samples for Grading Pancreatic
      Neuroendocrine Tumors.
AB  - Neuroendocrine pancreatic tumors (PanNETs) are graded on the basis of their
      proliferative activity. Cytological samples are commonly the only samples
      available, but the determination of Ki-67 in cytology and its reliability as a
      measure of tumor mitotic activity is not well settled. We have retrospectively
      reviewed all the cases of FNA under EUS control of PanNETs in a 10-year period
      (2006-2016) in the Hospital Clinico San Carlos (Madrid). We identified 10 PanNET
      cases with histological correlation. Median age was 49.4 years and the patients
      were mainly women. PanNETs were located more frequently in the tail of the
      pancreas, with a median size of 33.8 mm. None of our cases was a grade 3 tumor.
      The seven grade 1 tumors confirmed in histology had consistent Ki-67 in cytology.
      In three cases (30 %), there were discrepancies between the Ki-67 index measured
      in cytology and histology, and the differences ranged from 2 to 15 %; all these
      cases were grade 2 tumors in histology and were graded as grade 1 tumors in FNA
      material. Our results are consistent with previous studies which showed
      understaging when tumor grade was assessed in cytological samples, mainly in G2
      tumors. Previous literature has shown that Ki-67 assessment in EUS-FNA samples is
      a useful tool to rule out G3 tumors, but can be problematic for distinguishing G1
      and G2 tumors.

PMID- 27688082
TI  - BIM-mediated apoptosis and oncogene addiction.

PMID- 27688081
TI  - TERT Promoter Mutation in an Aggressive Cribriform Morular Variant of Papillary
      Thyroid Carcinoma.
AB  - The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare
      thyroid neoplasm characterized by unique morphologic findings and association
      with familial adenomatous polyposis. The biologic behavior of this variant has
      been reported to behave similarly to classic PTC. We report a rare sporadic case
      of CMV-PTC occurring in a 45-year-old female with multiple lymph nodes and bone
      metastases, which were detected after total thyroidectomy and radioactive iodine
      remnant ablation. Molecular analyses of primary thyroid and metastatic tumor
      tissues revealed a telomerase reverse transcriptase (TERT) promoter mutation, but
      absence of BRAF, KRAS, NRAS, HRAS, and PIK3CA mutations. Over a 4-year follow-up
      period, structurally identifiable bone metastases were persistent, but serial
      post-operative serum thyroglobulin levels remained undetectable in the absence of
      thyroglobulin antibody. The literature was reviewed. This is the first case of
      aggressive CMV-PTC showing TERT promoter mutation. TERT promoter mutations may
      help in predicting aggressive clinical behavior in CMV-PTC. Postoperative serum
      thyroglobulin measurement may have no impact on clinical decision-making in this
      type of tumor.

PMID- 27688083
TI  - Leptin and leptin receptors in salivary glands of primary Sjogren's syndrome.
AB  - BACKGROUND: The role of leptin in primary Sjogren's syndrome (SS) pathogenesis is
      unknown. The aim of this study was to investigate the expression of leptin and
      leptin receptor (LEPR) in minor salivary glands in patients with SS. MATERIALS
      AND METHODS: The expression of leptin and LEPR in minor salivary gland specimens
      obtained from patients with primary SS (n=50) and control subjects (n=50) were
      examined using immunohistochemical staining. RESULTS: Acinar cells, epithelial
      cells and adipocytes in salivary glands can express leptin and LEPR. It was
      observed that there was intense staining in the focal lymphocytic infiltration
      areas in SS patients. The intensity of leptin and LEPR staining under microscopy
      (400*) were graded semiquantitatively as negative, mild, moderate or strongly
      positive, and scored as 1, 2 or 3, respectively. The expression levels of leptin
      and LEPR in patients with primary SS were not higher than in controls. There was
      no significant difference in degrees of leptin and LEPR staining, staining
      intensity, and immunoreactive scores between groups. The expression of leptin and
      LEPR were not correlated with autoantibodies such as RF, ANA, anti-Ro, and/or
      anti-La positivity. CONCLUSIONS: These findings indicate that leptin and its
      receptors do not play an important role in primary SS pathophysiology.

PMID- 27688084
TI  - "Diabetic nephropathy" in a non-diabetic patient.
AB  - Kimmelstiel and Wilson originally described nodular glomerulosclerosis as the
      pathognomonic lesion of diabetic nephropathy. Nevertheless, nodular
      glomerulosclerosis pattern can rarely occur in non-diabetic patients. In such
      cases, the differential diagnosis includes membranoproliferative
      glomerulonephritis, light or heavy chain deposition disease, amyloidosis,
      fibrillary and immunotactoid glomerulonephritis and chronic hypoxic or ischemic
      conditions. In cases that the above entities cannot be proven, the term
      idiopathic nodular glomerulosclerosis is given. Here, we report a case of a male
      patient with renal failure stage IV and non-nephrotic range proteinuria. He had a
      history of heavy smoking and hypertension. The kidney biopsy revealed diabetic
      like lesions. However, there was no evidence of glucose impairment despite the
      thorough work-up at the biopsy time and thereafter. The laboratory data and the
      electron microscopy of the specimen could not prove any other cause of nodular
      glomerulosclerosis, and the final diagnosis was idiopathic nodular
      glomerulosclerosis. Moreover, we focus on the pathological differential diagnosis
      and work-up.

PMID- 27688085
TI  - Differentiation and prognostic markers in ampullary cancer: Role of p53, MDM2,
      CDX2, mucins and cytokeratins.
AB  - INTRODUCTION: Subclassification of ampullary adenocarcinomas into intestinal and
      pancreatobiliary type has prognostic and therapeutic implications.
      Immunohistochemical staining against specific biomarkers has been proven to be a
      useful adjunct in determining the exact histotype. Furthermore the
      immunohistochemical profile is suggestive of the molecular pathogenic mechanisms
      through which the tumor evolved. The aim of this study was to correlate p53,
      MDM2, CK7, CK20, MUC1, MUC2 and CDX2 expression in ampullary adenocarcinomas with
      the type of differentiation and patients' survival. MATERIAL AND METHODS: Forty
      seven radically resected ampullary adenocarcinomas were included in this study.
      Thirty-eight of them were eligible for survival analysis. Patients' data were
      retrospectively collected. All tumors were classified as intestinal or
      pancreatobiliary type, according to histologic criteria, and
      immunohistochemically stained against the aforementioned markers. RESULTS: There
      were 18 intestinal and 29 pancreatobiliary type ampullary adenocarcinomas. A
      trend was found between intestinal type tumors and large tumor size. CK20, MUC2
      and CDX2 expression was more prevalent in intestinal type tumors, while MUC1 was
      more frequently expressed in pancreatobiliary type tumors. Neither p53 nor MDM2
      differential expression between the two histotypes reached statistical
      significance. Multivariate analysis indicated CK20 and MUC1 as independent
      predictors of the histotype. Mean and median survival was 90.3 and 55 months
      respectively. Overall 5-year survival rate was 48%. Survival analysis indicated
      TNM stage as the only independent prognostic factor. Although significant
      difference in survival rates among the two histotypes was implied based on
      survival plots, this difference could not gain statistical significance.
      CONCLUSION: Immunoreactivity against CK20 and MUC1 in ampullary carcinomas is a
      useful adjunct to histologic examination in determining histotype. None of the
      immunohistochemical markers studied has prognostic significance. Future studies
      focused on other signaling pathways should seek further evidence of distinct
      tumorigenic mechanisms between histotypes of ampullary adenocarcinoma.

PMID- 27688086
TI  - Presence of high risk HPV DNA but indolent transcription of E6/E7 oncogenes in
      invasive ductal carcinoma of breast.
AB  - BACKGROUND AND AIMS: The causative role of high risk human papillomavirus (HR
      HPV) in breast cancer development is controversial, though a number of reports
      have identified HR-HPV DNA in breast cancer specimens. Nevertheless, most studies
      to date have focused primarily on viral DNA rather than the viral transcription.
      The aim of this study was to investigate the presence of HR-HPV in breast cancer
      tissues at HPV DNA level and HPV oncogenes mRNA level by in situ hybridization
      (ISH). METHODS: One hundred and forty six (146) cases of breast invasive ductal
      carcinoma(IDC) and 83 cases of benign breast lesions were included in the study.
      Type specific oligonucleotide probes were used for the DNA detection of HPV 16,18
      and 58 by ISH. HR-HPV oncogenes mRNA was assayed by novel RNAscope HR-HPV HR7
      assay ISH. p16 protein expression was evaluated by immunohistochemistry (IHC).
      RESULTS: HR-HPV 16,18 and 58 DNA were detected in 52 out of 146 (35.6%) IDC and
      in 3 out of 83 (3.6%) benign breast lesions by ISH. The HR-HPV mRNAs was detected
      only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered
      cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16
      over-expression did not correlate with the HPV DNA positive breast cancer
      samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731). CONCLUSIONS: HR-HPVs certainly
      exist in breast cancer tissue with less active transcription, which implies that
      the causal role of HPV in breast cancer development need further study.

PMID- 27688087
TI  - B-lymphoblastic leukemia in a patient with chronic lymphocytic leukemia:
      Sequential development of biclonal B-cell neoplasms over a 23-year period in a
      single individual.
AB  - Chronic lymphocytic leukemia (CLL) is an indolent mature B-cell neoplasm. During
      a prolonged disease course, a secondary B-cell neoplasm may arise in some
      patients, the most common example being the clonal evolution of CLL to diffuse
      large B-cell lymphoma, which is referred to as Richter transformation. Secondary
      de novo mature B-cell neoplasms arising in a patient with pre-existing CLL have
      been described; however, B-lymphoblastic leukemia (B-ALL) developing in untreated
      CLL is rare, and its clonal relationship to the primary neoplasm has been an
      interesting issue. Herein, we report an unusual case of the sequential
      development of CLL and B-ALL over a 23-year period in a 64-year-old male.
      Examination of the peripheral blood smear and bone marrow biopsy demonstrated
      dual neoplastic populations: small mature lymphocytes consistent with those seen
      in CLL and a population of blasts that were confirmed to be B-ALL by
      immunophenotyping. The biclonality of these two B-cell neoplasms was supported by
      cytogenetic studies. While an intrinsic immunodeficiency in patients with CLL may
      predispose them to the development of other malignancies, the pathogenesis of
      this unusual phenomenon remains to be further investigated.

PMID- 27688088
TI  - Diagnostic roles of MUC1 and GLUT1 in differentiating thymic carcinoma from type
      B3 thymoma.
AB  - MUC1 is a transmembrane mucin that has been related to tumor progression and
      outcome in various malignancies. GLUT1 is a member of the mammalian facilitative
      glucose transporter (GLUT) family of passive carriers that functions as an energy
      independent system for transporting glucose. Both of them are useful markers for
      the diagnosis, progression, and prognosis of various tumors, especially those
      that are cancerous. However, the clinical significance of MUC1 and GLUT1 in
      thymic epithelial tumors remains uncertain due to a lack of quality specimen and
      studies at sufficient scale, both owing, in part, to the rarity of the tumors.
      The aim of this article is to study the expression patterns of MUC1 and GLUT1 in
      thymic carcinoma and type B3 thymoma, and to evaluate their diagnostic value for
      these two types of tumors via immunohistochemistry. Forty-three patients were
      included in the study, including twenty-two with thymic carcinoma and twenty-one
      with type B3 thymoma. Tumor tissue sections were immunohistochemically stained
      for MUC1 and GLUT1; meanwhile, some tumors were also stained with CKpan, TDT,
      CD5, and CD117. MUC1 was expressed in a total of 17 cases, with a positive rate
      of 77.27% (17/22) in thymic carcinoma and 9.52% (2/21) in type B3 thymoma,
      revealing a significant difference (p<0.0001). A significant difference
      (p<0.0001) was also shown for GLUT1, where the positive rates for thymic
      carcinoma and type B3 thymoma were 100% (22/22) and 42.86% (9/21), respectively.
      The expression of MUC1 was significantly correlated with GLUT1 (p<0.0001).
      Furthermore, GLUT1 staining sensitivity and specificity for thymic carcinoma were
      100% (22/22) and 70.97% (22/31), respectively, while MUC1 staining sensitivity
      and specificity were 77.27% (17/22) and 89.47% (17/19), respectively. In
      conclusion, our study shows that MUC1 and GLUT1 staining may play a useful role
      in differentiating thymic carcinoma from type B3 thymoma, with high sensitivity
      and specificity.

PMID- 27688089
TI  - Corrigendum to "Short-range cytokine gradients to mimic paracrine cell
      interactions in vitro" [J. Control. Release 224 (2016) 59-68].

PMID- 27688090
TI  - Metabolomic study of two rice lines infected by Rhizoctonia solani in negative
      ion mode by CE/TOF-MS.
AB  - Rhizoctonia solani is a fungal pathogen that causes sheath blight disease in rice
      plants. In this study, metabolomic analysis using CE/TOF-MS in negative ion mode
      was used to investigate the resistance response of resistant and susceptible rice
      lines (32R and 29S, respectively) due to R. solani infection. Two rice lines
      showed different responses to the infection of R. solani. In 32R, R. solani
      infection induced significant increases in adenosine diphosphate (ADP), glyceric
      acid, mucic acid and jasmonic acid. In 29S, inosine monophosphate (IMP) was
      involved in the plant response to R. solani infection. Phenol compounds showed an
      increase as a response of the rice lines to R. solani infection. The study
      suggests that R. solani infection effects in 32R are associated with the
      induction of plant metabolic processes such as respiration, photorespiration,
      pectin synthesis, and lignin accumulation. In 29S, the R. solani infection is
      suggested to correlate with nitrogen metabolism.

PMID- 27688091
TI  - Antioxidative response in variegated Pelargonium zonale leaves and generation of
      extracellular H2O2 in (peri)vascular tissue induced by sunlight and paraquat.
AB  - In this study we exposed variegated leaves of Pelargonium zonale to strong
      sunlight (>1100MUmolm-2s-1 of photosynthetically active radiation) with and
      without paraquat (Pq), with the aim to elucidate the mechanisms of H2O2
      regulation in green and white tissues with respect to the photosynthetically
      dependent generation of reactive oxygen species (ROS). Sunlight induced marked
      accumulation of H2O2 in the apoplast of vascular and (peri)vascular tissues only
      in green sectors. This effect was enhanced by the addition of Pq. In the presence
      of diphenyl iodide, an NADPH oxidase inhibitor, H2O2 accumulation was abolished.
      Distinct light-induced responses were observed: in photosynthetic cells, sunlight
      rapidly provoked ascorbate (Asc) biosynthesis and an increase of glutathione
      reductase (GR) and catalase activities, while in non-photosynthetic cells, early
      up-regulation of soluble ascorbate peroxidase, dehydroascorbate reductase (DHAR)
      and GR activities was observed. Paraquat addition stimulated DHAR and GR
      activities in green sectors, while in white sectors activities of
      monodehydroascorbate reductase, DHAR and class III peroxidases, as well as Asc
      content rapidly increased. Differential antioxidative responses in the two
      tissues in the frame of their contrasting metabolisms, and the possible role of
      (peri)vascular H2O2 in signaling were discussed.

PMID- 27688092
TI  - The alkaline tolerance in Lotus japonicus is associated with mechanisms of iron
      acquisition and modification of the architectural pattern of the root.
AB  - The response of fifty-four Lotus japonicus ecotypes, and of six selected ecotypes
      was investigated under alkaline conditions. Sensitive, but not tolerant ecotypes,
      showed interveinal chlorosis under all alkalinity conditions and high mortality
      under extreme alkalinity. Interveinal chlorosis was associated with Fe
      deficiency, as a reduced Fe2+ shoot content was observed in all sensitive
      ecotypes. In addition, some showed a decline in photosynthesis rate and PSII
      performance compared to the control. In contrast, some tolerant ecotypes did not
      change these parameters between treatments. Alkaline tolerance could be explained
      by a mechanism of Fe acquisition and a root structural modification. This
      conclusion was based on the fact that all tolerant, but not the sensitive
      ecotypes, presented high ferric reductase oxidase activity under alkaline stress
      compared to the control, and a Herringbone root pattern modification. On this
      basis, the analysis of these mechanisms of alkaline tolerance could be used in
      screening programs for the selection of new tolerant genotypes in the Lotus
      genus.

PMID- 27688093
TI  - Genomic Insights Into Sepsis Course Using Whole Exome Sequencing.

PMID- 27688094
TI  - Zika Virus Strains Potentially Display Different Infectious Profiles in Human
      Neural Cells.
AB  - The recent Zika virus (ZIKV) epidemic has highlighted the poor knowledge on its
      physiopathology. Recent studies showed that ZIKV of the Asian lineage,
      responsible for this international outbreak, causes neuropathology in vitro and
      in vivo. However, two African lineages exist and the virus is currently found
      circulating in Africa. The original African strain was also suggested to be
      neurovirulent but its laboratory usage has been criticized due to its multiple
      passages. In this study, we compared the French Polynesian (Asian) ZIKV strain to
      an African strain isolated in Central African Republic and show a difference in
      infectivity and cellular response between both strains in human neural stem cells
      and astrocytes. Consistently, this African strain led to a higher infection rate
      and viral production, as well as stronger cell death and anti-viral response. Our
      results highlight the need to better characterize the physiopathology and predict
      neurological impairment associated with African ZIKV.

PMID- 27688095
TI  - Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated
      Aneurysmal Growth Through Disturbed Downstream TGF-beta Signaling.
AB  - Aneurysm-osteoarthritis syndrome characterized by unpredictable aortic aneurysm
      formation, is caused by SMAD3 mutations. SMAD3 is part of the SMAD2/3/4
      transcription factor, essential for TGF-beta-activated transcription. Although
      TGF-beta-related gene mutations result in aneurysms, the underlying mechanism is
      unknown. Here, we examined aneurysm formation and progression in Smad3-/-
      animals. Smad3-/- animals developed aortic aneurysms rapidly, resulting in
      premature death. Aortic wall immunohistochemistry showed no increase in
      extracellular matrix and collagen accumulation, nor loss of vascular smooth
      muscle cells (VSMCs) but instead revealed medial elastin disruption and
      adventitial inflammation. Remarkably, matrix metalloproteases (MMPs) were not
      activated in VSMCs, but rather specifically in inflammatory areas. Although Smad3
      /- aortas showed increased nuclear pSmad2 and pErk, indicating TGF-beta receptor
      activation, downstream TGF-beta-activated target genes were not upregulated.
      Increased pSmad2 and pErk staining in pre-aneurysmal Smad3-/- aortas implied that
      aortic damage and TGF-beta receptor-activated signaling precede aortic
      inflammation. Finally, impaired downstream TGF-beta activated transcription
      resulted in increased Smad3-/- VSMC proliferation. Smad3 deficiency leads to
      imbalanced activation of downstream genes, no activation of MMPs in VSMCs, and
      immune responses resulting in rapid aortic wall dilatation and rupture. Our
      findings uncover new possibilities for treatment of SMAD3 patients; instead of
      targeting TGF-beta signaling, immune suppression may be more beneficial.

PMID- 27688096
TI  - The miR-367-3p Increases Sorafenib Chemotherapy Efficacy to Suppress
      Hepatocellular Carcinoma Metastasis through Altering the Androgen Receptor
      Signals.
AB  - The androgen receptor (AR) was found to suppress hepatocellular carcinoma (HCC)
      metastasis at late stages. Due to this discovery, we searched for some AR
      enhancers to increase the efficacy of Sorafenib chemotherapy, and identified the
      microRNA (miR)-367-3p, whose expression is positively correlated with AR
      expression in advanced HCC, as an HCC metastasis suppressor. Combining miR-367-3p
      with Sorafenib showed better efficacy to suppress HCC cell invasion in vitro and
      in vivo. Mechanism dissection revealed that miR-367-3p could increase AR
      expression via directly targeting the 3'UTR of MDM2 to decrease MDM2 protein
      expression. The resultant increase of AR expression might then promote the
      expression of FKBP5 and PHLPP, thus dephosphorylating and inactivating AKT and
      ERK, to suppress the HCC cell invasion. Interestingly, the suppression of pAKT by
      miR-367-3p could subsequently attenuate the phosphorylation of AR and MDM2,
      giving rise to additional enhancement of AR protein expression, effectively
      forming a positive feedback loop. Together, these results suggest that miR-367-3p
      may function as an AR enhancer to increase Sorafenib chemotherapy efficacy via
      altering the MDM2/AR/FKBP5/PHLPP/(pAKT and pERK) signals to better suppress HCC
      metastasis. Successful development of this newly combined chemotherapy in the
      future may help us to better suppress the HCC metastasis at late stages.

PMID- 27688098
TI  - The development of a liquid biopsy for head and neck cancers.
AB  - Developing non-invasive diagnostic tools in the field of head and neck oncology
      has been a challenge. Analysis of circulating tumour derivatives in a patient's
      blood has been explored in other solid cancers. This includes analysis of
      circulating tumour DNA, intact circulating tumour cells (CTCs) and exosomes.
      These circulating tumour derivatives provide avenues of investigation which can
      be representative of a patient's primary tumour signature and can be assessed
      from a patient's blood sample. In advanced stage cancer patients, these tumour
      derivatives are found in higher amounts, attributed to higher cellular turnover
      (apoptosis, autophagy), lysed CTCs and sloughing from necrotic tumours. Head and
      neck squamous cell carcinoma (HNSCC) patients often present with advanced disease
      associated with a poor 5-year survival of <50%. Outside of sophisticated imaging
      and clinical examination, there is a lack of available biomarkers to measure
      disease burden, and/or response to therapy. Implementation of a liquid biopsy in
      HNSCC through serial blood samples has the potential to detect metastatic events
      earlier, thereby allowing better selection of appropriate treatment choices,
      predict prognosis in patients with potentially curable disease, monitor systemic
      therapies and residual disease post-treatment.

PMID- 27688097
TI  - nab-Paclitaxel, cisplatin, and 5-fluorouracil followed by concurrent cisplatin
      and radiation for head and neck squamous cell carcinoma.
AB  - OBJECTIVES: We previously reported the efficacy of nab-paclitaxel added to
      cisplatin, 5-FU, and cetuximab (APF-C) followed by concurrent high dose bolus
      cisplatin and radiation therapy (CRT) in patients with locally advanced head and
      neck squamous cell carcinoma (HNSCC). In this phase II trial, we determined the
      efficacy of APF (without cetuximab) followed by CRT in similar patients.
      MATERIALS AND METHODS: Eligible patients had stage III-IV oropharynx (OP),
      larynx, or hypopharynx SCC and adequate organ function and performance status. T1
      tumors were excluded. Patients were treated with three cycles of APF followed by
      CRT. Efficacy endpoints included two-year disease-specific survival (DSS),
      progression-free survival (PFS), overall survival (OS), and relapse rate.
      RESULTS: Thirty patients were enrolled. Most patients were smokers (77%) with
      bulky T3/4 (73%) and N2/3 (83%) tumors. Analyses were stratified for human
      papilloma virus (HPV) status: HPV-related OPSCC (n=17; 57%) and HPV-unrelated
      HNSCC (n=13; 43%). With a minimum follow-up of 21months, relapse occurred in 1
      (3%) patient. Two-year DSS was 94% in HPV-related OPSCC and 100% in HPV-unrelated
      HNSCC. Two-year PFS was 94% in HPV-related OPSCC and 100% in HPV-unrelated HNSCC.
      Two-year OS was 94% in HPV-related OPSCC and 92% in HPV-unrelated HNSCC. Causes
      of death were relapse (1), treatment-related mortality (1), and co-morbidity (1).
      Two patients with HPV-unrelated HNSCC treated with APF declined CRT and remained
      free of relapse at 36 and 28months of follow-up. CONCLUSION: This phase II trial
      demonstrated favorable two-year DSS, PFS, and OS and a low relapse rate in HPV
      unrelated HNSCC and HPV-related OPSCC treated with APF followed by CRT.

PMID- 27688099
TI  - Oral cancer: Deregulated molecular events and their use as biomarkers.
AB  - Oral Cancer (OC) is a subset of head and neck cancer (HNC) with an annual
      worldwide incidence of 275,000 cases. OC remains a significant burden worldwide
      in terms of diagnosis, treatment and prognosis. Despite desirable outcomes in
      early diagnosed OCs and treatment advances most OCs are detected in advanced
      stages. The 5-year survival rate of early-stage disease is ~80% and that of late
      stage disease is only ~20%. Recurrence and chemoresistance from a treatment point
      of view and pain and disfiguration are important factors contributing to the high
      morbidity and mortality of OC. Furthermore the process of oral carcinogenesis is
      complex and not yet fully understood. Consequently numerous potential biomarkers
      have been hypothesised though controversial results across the board hamper their
      clinical implementation. Of greatest advantage would be biomarkers signalling
      early events preceeding OC. Biomarker targets predominately involve deregulated
      molecular events that participate in cell signalling, growth, survival, motility,
      angiogenesis and cell cycle control but can also use changes in metabolic genes
      to discriminate healthy form disease state. Promising potential biomarkers
      include the growth signalling oncogenes, Epidermal Growth Factor Receptor and
      Cyclin D1, the anti-growth signalling components p53 and p21, apoptotic effectors
      such as Bcl-2 and also components involved in immortalisation, angiogenesis,
      invasion and metastasis processes. Translation of these potential biomakers to
      the patients is closer than ever though few issues remain to be resolved. Firstly
      large clinical trials are needed to validate their clinical applicability but
      also standardised methods of collection, storage and processing methods are
      needed to minimise variability.

PMID- 27688100
TI  - Patterns of failure after reirradiation with intensity-modulated radiation
      therapy and the competing risk of out-of-field recurrences.
AB  - PURPOSE: To describe patterns of failure (POF) after reirradiation (reRT) with
      intensity modulated radiation therapy (IMRT) for recurrent/second primary
      squamous cell carcinoma of the head and neck. METHODS: From 08/2004-02/2013, 75
      consecutive patients received reRT with IMRT. Gross tumor was generally treated
      with a 5mm planning target volume (PTV) margin. For postoperative cases, a 5mm
      PTV was added to the clinical target volume which included the postoperative bed.
      Elective neck coverage was not standard. POF were characterized by correlating
      the recurrent tumor location on CT-imaging with the reRT IMRT plan. RESULTS:
      Patients received definitive reRT (55%) or postoperative reRT (45%) to a median
      60Gy (range, 59.4-70Gy). Most patients (88%) received concurrent chemotherapy
      including induction (16%). The median overall survival was 1.8years. Isolated
      local-regional recurrence (LRR) was the most common failure-type (2-year
      cumulative incidence [CI] 22.5% [95% C.I. 13.6-32.7%]), but concurrent LRR and
      distant-failure occurred frequently (2-year CI LRR+distant-failure 19.6% [95%
      C.I. 11.3-29.5%]); isolated distant-failure was rare (2-year CI 5.7% [95% C.I.
      1.8-12.8%]). The 2-year in-field control was 65% (95% C.I. 52-81%) reflecting
      encouraging control within the irradiated target. Patients with gross disease
      were more likely to recur in-field (p=0.02), whereas postoperative patients were
      more likely to recur out-of-field/marginally than in-field (p=0.02). CONCLUSIONS:
      POF after reRT differ when treating gross disease or postoperatively and should
      be considered when delineating reRT targets. Aggressive local therapy resulted in
      favorable in-field control, yet there remains a high competing risk of regional
      and distant micrometastatic disease. Better systemic agents are needed to control
      clinically occult local-regional and distant disease.

PMID- 27688101
TI  - The effect of human papillomavirus on DNA repair in head and neck squamous cell
      carcinoma.
AB  - Much of the current literature regarding the molecular pathophysiology of human
      papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has focused
      on the virus's effect on cell cycle modulation and cell proliferation. A second
      mechanism of pathogenicity employed by HPV, dysregulation of cellular DNA repair
      processes, has been more sparsely studied. The purpose of this review is to
      describe current understanding about the effect of HPV on DNA repair in HNSCC,
      taking cues from cervical cancer literature. HPV affects DNA-damage response
      pathways by interacting with many proteins, including ATM, ATR, MRN, gamma-H2AX,
      Chk1, Chk2, p53, BRCA1, BRCA2, RAD51, Rb-related proteins 107 and 130, Tip60, and
      p16INK4A. Further elucidation of these pathways could lead to development of
      targeted therapies and improvement of current treatment protocols.

PMID- 27688102
TI  - PARTNER: An open-label, randomized, phase 2 study of docetaxel/cisplatin
      chemotherapy with or without panitumumab as first-line treatment for recurrent or
      metastatic squamous cell carcinoma of the head and neck.
AB  - OBJECTIVE: This phase 2 estimation study evaluated docetaxel/cisplatin
      with/without panitumumab, an anti-epidermal growth factor receptor monoclonal
      antibody, as first-line therapy for recurrent/metastatic squamous cell carcinoma
      of the head and neck (SCCHN). PATIENTS AND METHODS: Randomized patients received
      docetaxel/cisplatin (75mg/m(2) each) with/without panitumumab (9mg/kg) in 21-day
      cycles. Patients randomized to panitumumab+chemotherapy could continue
      panitumumab monotherapy after completing six chemotherapy cycles without
      progression; patients randomized to chemotherapy alone could receive second-line
      panitumumab after progression. Progression-free survival (PFS) was the primary
      endpoint. Secondary endpoints included overall survival (OS), overall response
      rate (ORR), time to response (TTR), duration of response (DOR), and safety. A
      protocol amendment limited enrollment to patients <70years owing to excess
      toxicity in older patients and added mandatory pegfilgrastim/filgrastim support.
      Outcomes were also analyzed by human papillomavirus status. RESULTS: 103 of the
      113 enrolled patients were evaluable and randomized to receive ?1 dose of first
      line treatment. Median PFS for panitumumab+chemotherapy was 6.9 (95% CI=4.7-8.3)
      months versus 5.5 (95% CI=4.1-6.8) months for chemotherapy alone (hazard ratio
      [HR]=0.629; 95% CI=0.395-1.002; P=0.048). ORR for panitumumab+chemotherapy was
      44% (95% CI=31-58%) versus 37% (95% CI=24-51%) for chemotherapy alone (odds ratio
      [OR]=1.37; 95% CI=0.57-3.33). Median OS for panitumumab+chemotherapy was 12.9
      (95% CI=9.4-18.5) months versus 13.8 (95% CI=11.8-22.9) months for chemotherapy
      alone (HR=1.103; 95% CI=0.709-1.717). Median TTR for panitumumab+chemotherapy
      treatment was 6.9weeks versus 11.0weeks for chemotherapy alone. Median DOR was
      8.0 (95% CI=5.7-11.1) months with panitumumab+chemotherapy versus 5.1 (95% CI=4.4
      7.2) months with chemotherapy alone. Grade 3/4 adverse event incidence was 73%
      with panitumumab+chemotherapy versus 56% with chemotherapy alone. 41% and 55% of
      patients in the panitumumab+chemotherapy and chemotherapy-alone arms,
      respectively, received panitumumab monotherapy. CONCLUSION: The addition of
      panitumumab to docetaxel/cisplatin may improve PFS in recurrent/metastatic SCCHN
      and has the potential to improve outcomes in these fully, or mostly, active
      patients.

PMID- 27688103
TI  - Oncologic outcomes and patient-reported quality of life in patients with
      oropharyngeal squamous cell carcinoma treated with definitive transoral robotic
      surgery versus definitive chemoradiation.
AB  - OBJECTIVE: It has been postulated that treatment outcomes are similar between
      transoral robotic surgery (TORS) and definitive chemoradiation (CRT) for
      oropharyngeal squamous cell carcinomas (OPSCC). We compared oncologic and quality
      of life (QOL) outcomes between definitive CRT and definitive TORS. MATERIALS AND
      METHODS: An observational comparison study was performed on 92 patients treated
      with TORS+/-adjuvant therapy and 46 patients treated with definitive CRT between
      July 2005 and January 2016. The Kaplan Meier method was used for survival
      analyses, and the Mann-Whitney test was used to compare QOL scores between
      groups. RESULTS: All patients had T0-T2 and N0-N2 disease, although CRT patients
      had higher clinical staging (p<0.001). HPV+ disease was present in 79% (n=73) of
      TORS patients and 91% (n=19) of tested CRT patients. Median follow-up was
      22.1months (range: 0.33-83.4). There were no significant differences in
      locoregional control or overall survival between CRT and TORS groups. Definitive
      TORS resulted in better saliva-related QOL than definitive CRT at 1, 6, 12, and
      24months (p<0.001, p=0.025, p=0.017, p=0.011). Among TORS patients, adjuvant
      therapy was associated with worse QOL in the saliva domain at 6, 12, and 24months
      (p<0.001, p<0.001, p=0.007), and taste domain at 6 and 12months (p=0.067,
      p=0.008). CONCLUSION: Definitive CRT and definitive TORS offer similar rates of
      locoregional control, overall survival, and disease-free survival in patients
      with early stage OPSCC. TORS resulted in significantly better short and long-term
      saliva-related QOL, whereas adjuvant therapy was associated with worse saliva and
      taste-related QOL compared to TORS alone.

PMID- 27688104
TI  - Diabetes mellitus, metformin and head and neck cancer.
AB  - INTRODUCTION: Diabetes mellitus (DM (Diabetes Mellitus)) is directly associated
      with some cancers. However, studies on the association between diabetes mellitus
      and head and neck cancer (HNC (Head and Neck Cancer)) have rendered controversial
      results. The objective of this study was to evaluate the association between DM
      and HNC, as well as the impact of metformin use on the risk of HNC. MATERIAL AND
      METHODS: This case-control study was conducted within the framework of the
      Brazilian Head and Neck Genome Project in 2011-2014. The study included 1021 HNC
      cases with histologically confirmed squamous cell carcinoma of the head and neck
      admitted to five large hospitals in Sao Paulo state. A total of 1063 controls
      were selected in the same hospitals. Odds ratios (OR) and 95% confidence
      intervals (CI) were estimated using unconditional logistic regression. RESULTS:
      Diabetic participants had a decreased risk of HNC (OR=0.68; 95% CI: 0.49-0.95)
      than non-diabetic participants, and this risk was further decreased among
      diabetic metformin users (OR=0.54; 95% CI: 0.29-0.99). Diabetic metformin users
      that were current smokers (OR=0.13; 95% CI: 0.04-0.44) or had an alcohol
      consumption of >40g/day (OR=0.31; 95% CI: 0.11-0.88) had lower risk of HNC than
      equivalent non-diabetic participants. CONCLUSION: The risk of HNC was decreased
      among diabetic participants; metformin use may at least partially explain this
      inverse association.

PMID- 27688105
TI  - Low etiologic fraction for human papillomavirus in larynx squamous cell
      carcinoma.
AB  - BACKGROUND: Human Papillomavirus (HPV) is a cause of oropharyngeal squamous cell
      carcinoma (OPSCC), but its pathogenic role in larynx squamous cell carcinoma
      (LSCC) remains unclear. MATERIAL AND METHODS: A single-institutional,
      retrospective case-series was performed to estimate the etiological fraction (EF)
      for HPV in LSCC. Eligible cases included 436 consecutive cases of LSCC diagnosed
      (2005-2014) at The Ohio State University Medical Center. HPV DNA presence was
      detected by consensus primer PCR (Inno-LiPa) and HPV type-specific qPCR. HPV
      E6/E7 mRNA expression was detected by type-specific qRT-PCR. Tumor p16 expression
      was evaluated by immunohistochemistry (IHC). RESULTS: HPV DNA was detected by
      Inno-LiPa in 54 of 404 (13.4%, 95% CI 10.2-17.1) evaluable samples but was
      confirmed by HPV type-specific qPCR in only 14 (3.5%, 95% CI 1.9-5.7). Only 7 of
      404 (1.7%, 95% CI 0.7-3.5) LSCC were positive for HPV E6/E7 mRNA expression,
      including HPV16 (n=4) and 1 each for 11, 26 and 33. In the HPV11-positive tumor,
      Sanger sequencing discovered 6 nucleotide mutations in the upstream regulation
      region, E6 and E7. Of 404 LSCC, 18 had strong and diffuse p16 expression. In
      comparison to a gold standard of HPV E6/E7 mRNA expression, p16 expression had a
      sensitivity of 71.4% (95% CI 29.0-96.3), specificity of 96.7% (95% CI 94.5-98.3),
      positive-predictive-value (PPV) of 27.8% (95% CI 9.7-53.5) and negative
      predictive-value of 99.5% (95% CI 98.1-99.9). CONCLUSION: The EF for HPV in LSCC
      is low (1.7%) in a geographic region with high EF for OPSCC. Low-risk HPV may
      rarely cause LSCC. Finally, p16 expression has poor PPV for HPV in LSCC.

PMID- 27688107
TI  - Trends of oral cavity, oropharyngeal and laryngeal cancer incidence in Scotland
      (1975-2012) - A socioeconomic perspective.
AB  - AIM: To examine current incidence trends (1975-2012) of oral cavity (OCC),
      oropharyngeal (OPC) and laryngeal cancer in Scotland by socioeconomic status
      (SES). METHODS: We included all diagnosed cases of OCC (C00.3-C00.9, C02-C06
      excluding C2.4), OPC (C01, C2.4, C09-C10, C14) and laryngeal cancer (C32) on the
      Scottish Cancer Registry (1975-2012) and annual midterm population estimates by
      age, sex, geographic region and SES indices (Carstairs 1991 and Scottish Index of
      Multiple Deprivation 2009). Age-standardized incidence rates were computed and
      adjusted Poisson regression rate-ratios (RR) compared subsites by age, sex,
      region, SES and year of diagnosis. RESULTS: We found 28,217 individuals (19,755
      males and 8462 females) diagnosed with head and neck cancer (HNC) over the study
      period. Between 1975 and 2012, relative to the least deprived areas, those living
      in the most deprived areas exhibited the highest RR (>double) of OCC, OPC and
      laryngeal cancer, and an almost dose-like response was observed between SES and
      HNC incidence. Between 2001 and 2012, this socioeconomic inequality tended to
      increase over time for OPC and laryngeal cancer but remained relatively unchanged
      for OCC. Incidence rates increased markedly for OPC, decreased for laryngeal
      cancer and remained stable for OCC, particularly in the last decade. Males
      exhibited significantly higher RRs compared to females, and the peak age of
      incidence of OPC was slightly lower than the other subsites. CONCLUSION: Contrary
      to reports that OPC exhibits an inverse socioeconomic profile, Scotland country
      level data show that those from the most deprived areas consistently have the
      highest rates of head and neck cancers.

PMID- 27688106
TI  - Quantitative body mass characterization before and after head and neck cancer
      radiotherapy: A challenge of height-weight formulae using computed tomography
      measurement.
AB  - OBJECTIVES: We undertook a challenge to determine if one or more height-weight
      formula(e) can be clinically used as a surrogate for direct CT-based imaging
      assessment of body composition before and after radiotherapy for head and neck
      cancer (HNC) patients, who are at risk for cancer- and therapy-associated
      cachexia/sarcopenia. MATERIALS AND METHODS: This retrospective single-institution
      study included 215 HNC patients, treated with curative radiotherapy between 2003
      and 2013. Height/weight measures were tabulated. Skeletal muscle mass was
      contoured on pre- and post-treatment CT at the L3 vertebral level. Three common
      lean body mass (LBM) formulae (Hume, Boer, and James) were calculated, and
      compared to CT assessment at each time point. RESULTS: 156 patients (73%) had
      tumors arising in the oropharynx and 130 (61%) received concurrent chemotherapy.
      Mean pretreatment body mass index (BMI) was 28.5+/-4.9kg/m(2) in men and 27.8+/
      8kg/m(2) in women. Mean post-treatment BMI were 26.2+/-4.4kg/m(2) in men, 26+/
      7.5kg/m(2) in women. Mean CT-derived LBM decreased from 55.2+/-11.8kg pre-therapy
      to 49.27+/-9.84kg post-radiation. Methods comparison revealed 95% limit of
      agreement of +/-12.5-13.2kg between CT and height-weight formulae. Post-treatment
      LBM with the three formulae was significantly different from CT (p<0.0001). In
      all instances, no height-weight formula was practically equivalent to CT within+/
      5kg. CONCLUSION: Formulae cannot accurately substitute for direct quantitative
      imaging LBM measurements. We therefore recommend CT-based LBM assessment as a
      routine practice of head and neck cancer patient body composition.

PMID- 27688108
TI  - A cohort study into head and neck cancer mortality in Belgium (2001-11): Are
      individual socioeconomic differences conditional on area deprivation?
AB  - OBJECTIVE: The aim of this study is to assess to what extent individual and area
      level socioeconomic position (SEP) are associated to head and neck cancer (HNC)
      mortality and to what extent they contribute to regional variation in HNC
      mortality in Belgium. MATERIALS AND METHODS: Data on men aged 40-64 are collected
      from a population based dataset based on the 2001 Belgian census linked to
      register data on emigration and mortality for 2001-2011. Individual SEP is
      measured using education, employment status and housing conditions. Deprivation
      at municipal level is measured by a deprivation index. Absolute mortality
      differences are estimated by age standardised mortality rates. Multilevel Poisson
      models are used to estimate the association and interaction between HNC mortality
      and individual and area-level SEP, and to estimate the regional variation in HNC
      mortality. RESULTS: HNC mortality rates are significantly higher for men with a
      low SEP and men living in deprived areas. Cross-level interactions indicate that
      the association between individual SEP and HNC mortality is conditional on area
      deprivation. HNC mortality in deprived areas is especially high among high-SEP
      men. As a result, social disparities appear to be smaller in more deprived areas.
      Regional variation in HNC mortality was significant. Population composition
      partially explains this regional variation, while area deprivation and cross
      level interactions explains little. CONCLUSION: Both individual and area-level
      deprivation are important determinants of HNC mortality. Underlying trends in
      incidence and survival, and risk factors, such as alcohol and tobacco use, should
      be explored further.

PMID- 27688109
TI  - Geographic variation in Medicare treatment costs and outcomes for advanced head
      and neck cancer.
AB  - BACKGROUND: Advanced head and neck cancer (HNC) is a complex group of diseases
      that requires the input and coordination of multiple providers. While there are
      general guidelines for treatment, there is also considerable variation in how
      patients are treated, and how long they survive after treatment. It is unclear
      how the treatment variations relate to treatment costs and survival. METHODS: We
      identified 3678 Medicare patients with advanced HNC treated in 12 US regions
      between 2004 and 2009 using the linked database containing Medicare and
      Surveillance Epidemiology and End Results (SEER) data. We calculated average cost
      per patient during the period three months before to 12months after diagnosis for
      each region. Costs included inpatient hospital, outpatient, physician, and
      durable medical equipment charges. We also calculated three-year overall survival
      for each of the regions. RESULTS: The mean cost-per-patient varied substantially
      among the regions, ranging from $51,857 for Utah to $82,181 for Detroit. Utah
      incurred the lowest total costs within one year of advanced HNC diagnosis
      ($51,857 per patient, 95% CI $42,285-$61,429), whereas Detroit had the highest
      costs ($82,181 per patient, 95% CI $74,752-$89,610). Overall survival also varied
      among the regions, ranging from 45months in Kentucky to 58months in Washington.
      There was little correlation between expenditures and length of survival, with
      correlation coefficient of 0.0088. CONCLUSION: Despite significant variation in
      both expenditures and survival among the regions, we found no correlation between
      costs and mean survival time, suggesting that more costly care did not lead to
      improved outcomes.

PMID- 27688110
TI  - A clinicopathologic study of head and neck rhabdomyosarcomas showing FOXO1 fusion
      positive alveolar and MYOD1-mutant sclerosing are associated with unfavorable
      outcome.
AB  - BACKGROUND: Based on their distinctive histologic and genetic features, the
      latest WHO classification of soft tissue tumors includes four pathologic variants
      of rhabdomyosarcoma (RMS): embryonal (ERMS), alveolar (ARMS), spindle cell
      sclerosing (SRMS-ScRMS) and pleomorphic RMS. The aim of this study focused on a
      detailed clinicopathologic and survival analysis of head and neck RMS (HNRMS)
      using the latest pathologic and molecular criteria reflecting this new
      subclassification in a large cohort. PATIENTS AND METHODS: Patients managed for
      HNRMS in our institution (1996-2015) were analyzed. The presence of a FOXO1
      fusion was required for the classification of ARMS. MYOD1 mutations in SRMS-ScRMS
      were tested when material available. Univariate and multivariate analyses were
      performed to evaluate variables related to overall survival (OS). RESULTS: Ninety
      nine HNRMS patients (52 males and 47 females, mean of 16years) were included in
      the study after pathologic re-review. The most common location was parameningeal
      (PM) (n=64), followed by non-orbital/non-PM (n=25) and orbital (n=10). There were
      53 ERMS, 33 fusion-positive ARMS and 13 SRMS-ScRMS [SRMS (8); ScRMS (5)]. The 5
      year OS rate for ERMS patients was significantly higher (82%) compared to ARMS
      (53%) and SRMS-ScRMS (50%) [SRMS (75%); ScRMS (30%)]. Univariate analysis showed
      that survival was dependent on histology (P=0.012), tumor size >5cm (P<0.001),
      regional lymph node involvement (P=0.002), metastasis at initial presentation
      (P<0.001), stage (P<0.001), and recurrence (P=0.002). Multivariate analysis
      confirmed histologic subtype to be significant (P=0.043). CONCLUSION: Our
      findings reinforce that HNRMS is a heterogenous disease with ARMS and SRMS-ScRMS
      having an equally unfavorable outcome.

PMID- 27688112
TI  - Induction chemotherapy for squamous cell carcinomas of the oral cavity: A
      cumulative meta-analysis.
AB  - Induction chemotherapy (ICT) is a controversial treatment for head and neck
      squamous cell carcinomas (HNSCC). Despite numerous randomized controlled trials
      (RCTs), a majority do not have enough statistical power alone to conclude ICT's
      treatment value among oral squamous carcinoma patients (OSCC) since many
      addressed HNSCC as one entity instead of by specific subtypes. By performing a
      systematic review and cumulative meta-analysis, we aim to determine the benefits
      of ICT in OSCC therapy. A literature search identified for RCTs comparing OSCC
      patients who received ICT against those without. Log-hazard ratio, and relative
      risk were used for comparison. Heterogeneity was determined using the I(2)
      statistic package. The primary endpoint was overall survival (OS), followed by
      disease-free survival (DFS), locoregional recurrence (LRR) and distant metastasis
      (DM) as secondary endpoints. RESULTS: 27 randomized trials were included for
      analysis (n=2872 patients). The shortest median follow-up was 15months whereas
      the longest was 11.5years. ICT does not improve OS (HR=0.947, 95% CI 0.85-1.05,
      p=0.318), DFS (RR=1.05, 95% CI 0.92-1.21, p=0.462) and DM (RR=0.626, CI 95% 0.361
      1.086, p=0.096) compared to locoregional treatment alone. However, there was a
      significant improvement to LRR (RR=0.778, 95% CI 0.622-0.972, p=0.027). There is
      no evidence ICT improves survival outcomes for OSCC patients. However, ICT
      reduces locoregional recurrence of OSCC, which may need further verification.

PMID- 27688113
TI  - Pretreatment pain predicts perineural invasion in oral squamous cell carcinoma: A
      prospective study.
AB  - OBJECTIVES: Perineural invasion (PNI) is an established poor prognostic
      pathological feature for oral squamous cell carcinoma (OSCC). The purpose of this
      study was to analyze the role of pretreatment parameters in predicting PNI for
      OSCC. MATERIALS AND METHODS: We prospectively enrolled into our study 102 newly
      diagnosed OSCC patients, who were surgically treated from 2011 to 2012. Before
      treatment, patients completed the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire H&N35 and the visual analogue
      scale (VAS) for cancer pain. Pathological examination was performed to ascertain
      PNI status in all patients. Patients were divided into two groups, those with PNI
      and without PNI. Pretreatment parameters were compared between the two groups.
      RESULTS: In univariate analysis, clinical T classification (P<0.001), painkiller
      use (P=0.001), problem with social eating (P<0.001) and social contact (P=0.002),
      VAS scores of primary pain (P<0.001) and referred pain (P=0.004) were found to be
      associated with PNI. Multivariate logistic regression analysis further revealed
      VAS score of primary pain (P=0.001, OR 2.014) and T3-4 classification (P=0.014,
      OR 6.422) were independent predictors of PNI. A regression equation incorporating
      pretreatment pain was developed to predict the probability of having PNI.
      CONCLUSION: PNI can be predicted by higher pretreatment VAS score of primary
      pain, as well as more advanced clinical T classification. Careful evaluation of
      pretreatment pain of primary tumor can thus be helpful in improving treatment
      decision making for OSCC.

PMID- 27688111
TI  - Prognostic significance of non-HPV16 genotypes in oropharyngeal squamous cell
      carcinoma.
AB  - OBJECTIVES: Recent studies have found that cases with oropharyngeal squamous cell
      carcinoma (OPSCC) positive for HPV16 genotype have better overall survival
      compared with cases positive for other HPV genotypes. We sought to further
      replicate these studies and determine if this relationship is modified by
      expression of p16 tumor suppressor protein. MATERIAL AND METHODS: We identified
      238 OPSCC cases from the Carolina Head and Neck Cancer Study (CHANCE) study, a
      population based case-control study. Tumors that tested positive solely for HPV16
      genotype and no other genotypes with PCR were classified as HPV16-positive.
      Tumors positive for any other high-risk HPV genotype were classified as non-HPV16
      positive. Expression of p16 in the tumor was determined with
      immunohistochemistry. Follow-up time was calculated from the date of diagnosis to
      date of death or December 31, 2013. Overall survival was compared with the Kaplan
      Meier curves and log-rank test. Hazard ratios (HR) adjusted for smoking, alcohol
      use, sex, race, and age was calculated with the Cox proportional hazard
      regression. RESULTS: Cases with HPV16-positive OPSCC had better overall survival
      than cases with non-HPV16-positive OPSCC (log-rank p-value: 0.010). When
      restricted to OPSCC cases positive for p16 expression, the same trend continued
      (log-rank p-value: 0.002). In the adjusted model, cases with non-HPV16-positive
      OPSCC had greater risk of death compared to cases with HPV16-positive tumors (HR:
      1.92; 95% CI: 1.03, 3.60). CONCLUSIONS: This finding indicates that HPV
      genotyping carries valuable prognostic significance in addition to p16 status and
      future survival studies of OPSCC should take into account differing HPV
      genotypes.

PMID- 27688114
TI  - Autophagy: A boon or bane in oral cancer.
AB  - Autophagy is a catabolic process involving cellular recycling and is believed to
      play a distinct role in cell survival especially when exposed to stressors,
      rendering it comparable to the elixir sustaining life. It plays a significant
      role in various conditions like cancers, neuropathies, heart diseases, auto
      immune diseases, etc. Its role in tumorigenesis and cancer therapeutics is worth
      exploring. Autophagy is believed to help in survival and longevity of cancer
      cells by buffering metabolic stress. Inhibition of autophagy in an environment of
      nutrient deprivation leads to cell death. Autophagy is also seen to facilitate
      metastasizing tumor cells in surviving the conditions of metabolic deprivation
      and in recovery when conditions turn favorable. Many current cancer therapies
      tend to inflict metabolic stress, thus autophagy inhibitors may be useful in
      cancer treatment. As per the adage, "excess of anything is bad", the autophagy
      promoters can also be exploited as beneficial tools in the fight against cancer.
      Another method for tumor-cell elimination can be by inducing autophagic cell
      death through over-stimulation. Oral cancers are becoming a leading cause of
      deaths worldwide. Much remains to be explored about the role autophagy plays in
      progression of head and neck cancers, so as to harness it in the therapeutics of
      these cancers. Research on autophagy is still in its infancy. There are knowledge
      gaps in understanding this complex process. But there is no doubt that
      understanding exact mechanism behind autophagy will open up new avenues in cancer
      therapeutics and even prevention.

PMID- 27688115
TI  - Does elimination of planned postoperative radiation to the primary bed in p16
      positive, transorally-resected oropharyngeal carcinoma associate with poorer
      outcomes?
AB  - OBJECTIVE: The purpose of our study is to compare oncologic and functional
      outcomes of p16-positive oropharyngeal squamous cell carcinoma (OPSCC) patients,
      in the presence and absence of planned radiation to the primary bed following
      transoral surgery (TOS), stratified by T-classification. METHODS: Retrospective
      cohort study of 261, T1-T4, consecutively TOS-treated OPSCC patients. RESULTS: At
      a median follow-up of 61months, local recurrence (LR) occurred in 6
      (2.3%)patients (3 each in T1-T2 and T3-T4 groups), of which 5 had tumors in the
      tongue base and one in the tonsil. Of patients not receiving planned primary bed
      radiation, LR occurred in 3% of T1-T2s versus 17% of T3-T4s. In patients with T1
      T2 tumors, Absolute Risk Reduction of LR with primary bed radiation was 3.26%
      (95% CI: -0.37%, 7%); Number Needed to Treat to prevent one LR was 31 (95% CI:
      14.5, 271). Absolute Risk Increase for gastrostomy-tube with primary bed
      radiation was 34.4% (95% CI: 24%, 45%); Number Needed to Harm was 3 (95% CI: 2.2,
      4.2), i.e., for every three patients with T1-T2 tumors receiving primary bed
      radiation, one had a gastrostomy-tube. CONCLUSIONS: Elimination of primary bed
      radiation in margin-negative resected, T1-T2 p16-positive OPSCC was not
      associated with significant compromise of local control, and correlated with
      superior swallowing preservation, assessed using gastrostomy rate as a surrogate.
      Lack of primary bed radiation in T3-T4 tumors associated with significantly
      increased LR rates.

PMID- 27688116
TI  - Prospective swallowing outcomes after IMRT for oropharyngeal cancer: Dosimetric
      correlations in a population-based cohort.
AB  - OBJECTIVES: To identify dose constraints to preserve swallowing after head and
      neck (H&N) radiotherapy using prospectively collected functional outcomes.
      MATERIALS AND METHODS: Stage III-IV oropharyngeal cancer patients were
      prospectively evaluated using the Royal Brisbane Hospital Outcome Measure for
      Swallowing and Performance Status Scale for H&N Cancer Patients at pre-treatment
      and 3, 6, 12, and 24months after intensity-modulated radiotherapy. Dosimetric
      parameters were correlated with swallowing function. RESULTS: Ninety-six patients
      were evaluated with median follow-up of 14.1months (interquartile range 9.9
      26.3). Six patients (8.3%) remained feeding tube (FT) dependent at 12months. At
      2years, 32.6% tolerated a normal diet without restrictions. Mean doses of 55Gy to
      supraglottic larynx, 44Gy to glottic larynx, 48Gy to cricopharyngeus, and 44Gy to
      esophageal inlet were associated with >25% risk of FT dependence at 6months.
      CONCLUSION: Higher mean doses to the larynx and pharyngo-esophageal junction were
      associated with longer duration of FT dependence and dietary restrictions.

PMID- 27688117
TI  - Comparison of spinal accessory dysfunction following neck dissection with
      harmonic scalpel and electrocautery - A randomized study.
AB  - INTRODUCTION: Harmonic scalpel is being increasingly used in neck dissection as
      alternative to conventional electro-cautery for achieving haemostasis. Use of
      harmonic scalpel has been shown to significantly reduce intra operative blood
      loss and intra operative time in neck dissection. But how safe is it with regards
      to nerve injury (spinal accessory nerve and other nerves) during neck dissection.
      We intended to study the spinal accessory nerve injury during neck dissection by
      both harmonic scalpel and electro cautery technique and compared postoperative
      recovery of shoulder function after neck dissection. METHODS: 40 patients
      undergoing selective neck dissection for primary oral malignancy were enrolled in
      this study. The Harmonic scalpel (HS) group consisted of 20 patients, and the
      electo cautery technique (ET) group had 20 patients. The following variables were
      examined: shoulder pain by visual analog scoring and shoulder function by means
      of degree of abduction and graded was grade I-0-90 degrees ; grade II-90-135
      degrees ; grade III-135-180 degrees . They assessment was done at the time of
      discharge, 1month and 3month and six month after surgery. RESULTS: Though
      shoulder pain was almost similar at 1st week and 1month, however at 2nd and 6th
      month shoulder pain was found to be significantly lesser in harmonic scalpel
      group as compared to electro cautery. At 1week more no of patients had restricted
      shoulder mobility in HS as compared to EC group. But at 6months the shoulder
      function was found to be significantly better in HS group as compared to EC group
      (p value<0.05). CONCLUSION: Spinal accessory nerve function recovery after
      selective neck dissection is better in HS group as compared to the electro
      cautery group.

PMID- 27688119
TI  - Tongue sole (Cynoglossus semilaevis) CD59: A complement inhibitor that binds
      bacterial cells and promotes bacterial escape from the killing of fish serum.
AB  - CD59 is a complement regulatory protein that inhibits the formation of membrane
      attack complex of complement. In this study, we examined the expression and
      activity of tongue sole (Cynoglossus semilaevis) CD59 (CsCD59). CsCD59 possesses
      the conserved structural features of CD59 and shares 33%-46% sequence identities
      with other fish CD59. Expression of CsCD59 was high in liver, spleen, and muscle,
      and was stimulated by infection of bacterial pathogens. Recombinant CsCD59
      (rCsCD59) exhibited an apparent inhibition effect on the activation of tongue
      sole serum complement. ELISA and microscopy detected binding of rCsCD59 to a
      number of Gram-negative and Gram-positive bacteria. Interaction with rCsCD59 did
      not affect bacterial viability but significantly enhanced bacterial resistance
      against the killing effect of fish serum. Together these results indicate that
      fish CD59 may to some degrees facilitate a general escape of bacteria from
      complement-mediated immunity.

PMID- 27688118
TI  - Single nucleotide polymorphisms as markers of genetic susceptibility for oral
      potentially malignant disorders risk: Review of evidence to date.
AB  - BACKGROUND: Oral cancers are preceded by oral potentially malignant disorders
      (OPMD). Understanding genetic susceptibility for OPMD risk could provide an
      opportunity for risk assessment of oral cancer through early disease course. We
      conducted a review of single nucleotide polymorphism (SNP) studies for OPMD risk.
      METHODS: We identified all relevant studies examining associations of SNPs with
      OPMD (leukoplakia, erythroplakia and oral sub-mucous fibrosis) conducted world
      wide between January, 2000 and February, 2016 using a combined keyword search on
      PubMed. Of these, 47 studies that presented results as odds ratios and 95% CI
      were considered for full review. RESULTS: The majority of eligible studies that
      explored candidate gene associations for OPMD were small (N<200 cases), limiting
      their scope to provide strong inference for any SNP identified to date in any
      population. Commonly studied SNPs were genes of carcinogen metabolism (n=18
      studies), DNA repair (n=11 studies), cell cycle control (n=8 studies), extra
      cellular matrix alteration (n=8 studies) and immune-inflammatory (n=6 studies)
      pathways. Based on significant associations as reported by two or more studies,
      suggestive markers included SNPs in GSTM1 (null), CCND1 (G870A), MMP3 (-1171;
      promotor region), TNFalpha (-308; rs800629), XPD (codon 751) and Gemin3
      (rs197412) as well as in p53 (codon 72) in Indian populations. However, an equal
      or greater number of studies reported null or mixed associations for SNPs in
      GSTM1 (null), p53 (codon 72), XPD (codon 751), XRCC (rs25487 C/T), GSTT1 (null)
      and CYP1A1m1 (MspI site). CONCLUSION: Candidate gene association studies have not
      yielded consistent data on risk loci for OPMD. High-throughput genotyping
      approaches for OPMD, with concurrent efforts for oral cancer, could prove useful
      in identifying robust risk-loci to help understand early disease course
      susceptibility for oral cancer.

PMID- 27688120
TI  - Characterisation of a new, highly effective method for detecting nematode eggs
      (Ascaris spp., Toxocara spp., Trichuris spp.) in sewage sludge containing
      flocculants.
AB  - Because traditional methods used for sewage sludge parasitological examinations
      have low sensitivity, a new, highly effective method (own method - OM) was
      devised. The principle of this method is to eliminate the flocculent effect on
      the structure of sewage sludge by mechanically damaging floccules in the presence
      of surfactants and to increase the effectiveness of egg isolation processes in
      large volumes of liquids. The objective of this study was to estimate the
      effectiveness of the OM in detecting nematode eggs in sewage sludge samples
      containing flocculants. In the first stage, the effectiveness of the OM was
      compared to 4 other methods routinely used in parasitological examinations of
      dehydrated sewage sludge. Next, method standardisation was performed using sewage
      sludge samples supplemented with eggs from 3 parasite species (Ascaris suum,
      Toxocara canis and Trichuris vulpis). The study demonstrated that OM efficiency
      was 6-65 times greater than other methods, depending on the method and type of
      detected eggs. Limit of detection (LOD) calculations for the OM were performed on
      samples supplemented with a known number of parasite eggs resulting in 10, 5 and
      3 eggs/50 g of sample for A. suum, T. vulpis and T. canis eggs, respectively. The
      limits of quantification (LOQ) of the OM were established as 200 eggs/50 g of
      sample for A. suum and T. vulpis eggs and 50 eggs/50 g of sample for T. canis
      eggs. The rectilinear regression functions, which determined the relationship
      between the number of eggs detected in OM measurements and the number of eggs
      contained in the samples, were characterised by high and statistically
      significant coefficients of determination (r2). The slopes of the trend lines
      were 0.3188, 0.3821 and 0.3276, and the intercepts were -11.223, -9.0261 and 
      23.15 for A. suum, T. canis and T. vulpis eggs, respectively. Method sensitivity,
      calculated as the slope coefficient of the regression function and expressed as a
      percentage, ranged from 32% to 38% depending on egg type. The study confirmed
      that the OM may be applied to quantify parasite eggs in dehydrated sewage sludge
      containing polyelectrolytes.

PMID- 27688121
TI  - Brain mechanism of itch in atopic dermatitis and its possible alteration through
      non-invasive treatments.
AB  - Atopic dermatitis (AD) is a common chronic skin disease that is characterized by
      intense pruritus and has high impairment of quality of life. AD is often
      described as "the itch that rashes, rather than the rash that itches". Several
      studies suggest that mechanisms of central modulation play an important role in
      the development and maintenance of chronic itch. Therefore, treating the
      neurosensory aspects of itch is an important part in the management of chronic
      itch. However, little attention has been paid to the role of the central nervous
      system in the processing of itch in AD. Targeting itch-related anatomical
      structures in the brain with non-invasive treatments such as psychological
      interventions and transcranial Direct Current Stimulation (tDCS) could have an
      antipruritic effect in AD. Therefore, in this review article, we discuss the
      current progress in brain imaging research of itch, as well as the efficacy of
      non-invasive interventions for itch relief in this patient group.

PMID- 27688122
TI  - Cardio-respiratory responses to hypoxia combined with CO2 inhalation during
      maximal exercise.
AB  - We measured the effects of adding CO2 to an inhaled hypoxic gas mixture on cardio
      respiratory parameters during maximal exercise. Eight young males performed four
      incremental maximal exercise tests on cycle under ambient air, hypoxia (FIO2
      0.125), inhaled CO2 (FICO2 0.045), and combination of hypoxia and inhaled CO2.
      The highest ventilation (VE) and VE/CO2 output were recorded in CO2 inhalation
      and combined treatments. Arterial O2 partial pressure was higher in combined than
      in hypoxia treatment, but the difference between the treatments narrowed from
      rest to end-exercise, at least partly because the magnitude of the increase in VE
      (%) at exercise was smaller in combined treatment than in hypoxia. Arterial O2
      content was higher in combined treatment than in hypoxia at rest, but no more at
      maximal exercise. Cardiac output was higher and O2 extraction lower when
      breathing O2-poor gas mixtures than under the two other treatments. For a given
      oxygen consumption, hypoxia and combined treatment showed similar cardiac output
      and O2 extraction.

PMID- 27688123
TI  - A family nursing educational intervention supports nurses and families in an
      adult intensive care unit.
AB  - The family experience of critical illness is filled with distress that may have a
      lasting impact on family coping and family health. A nurse can become a source of
      comfort that helps the family endure. Yet, nurses often report a lack of
      confidence in communicating with families and families report troubling
      relationships with nurses. In spite of strong evidence supporting nursing
      practice focused on the family, family nursing interventions often not
      implemented in the critical care setting. This pilot study examined the influence
      of an educational intervention on nurses' attitudes towards and confidence in
      providing family care, as well as families' perceptions of support from nurses in
      an adult critical care setting. An academic-clinical practice partnership used
      digital storytelling as an educational strategy. A Knowledge to Action Process
      Framework guided this study. Results of pre-intervention data collection from
      families and nurses were used to inform the educational intervention. A
      convenience sample of family members completed the Iceland Family Perceived
      Support Questionnaire (ICE-FPSQ) to measure perception of support provided by
      nurses. Video, voice, and narrative stories of nurses describing their
      experiences caring for family members during a critical illness and family
      members' experiences with a critically ill family member also guided education
      plans. When comparing the pre and post results of the Family Nurse Practice Scale
      (FNPS), nurses reported increased confidence, knowledge, and skill following the
      educational intervention. Qualitative data from nurses reported satisfaction with
      the educational intervention. Findings suggest that engaging nurses in
      educational opportunities focused on families while using storytelling methods
      encourages empathic understandings. Academic-clinician teams that drive
      directions show promise in supporting families and nurses in critical care
      settings. Plans are moving forward to use this study design and methods in other
      critical care settings.

PMID- 27688124
TI  - Association between abnormal default mode network activity and suicidality in
      depressed adolescents.
AB  - BACKGROUND: Suicide is the second leading cause of death among 15- to 29-year
      olds in China, and 60 % of suicidal patients have a history of depression.
      Previous brain imaging studies have shown that depression and suicide may be
      associated with abnormal activity in default mode network (DMN) regions. However,
      no study has specifically investigated the relationship between DMN functional
      activity and suicidal behavior in depressed individuals. Therefore, in the
      present study, we directly investigated features of DMN brain activity in
      adolescent patients with histories of depression and attempted suicide. METHODS:
      A total of 35 sex- and age-matched suicidal depressed patients were compared with
      18 non-suicidal depressed patients and 47 healthy controls. We explored
      functional activity changes in DMN regions that could be associated with suicidal
      behavior by comparing resting-state functional magnetic resonance imaging (rs
      fMRI) signals using independent component analysis (ICA). Scores on six clinical
      scales that measure depression severity (Hamilton Depression Scale (HDRS) and
      Beck Depression Inventory (BDI)) and suicidal traits (Barratt Impulsiveness Scale
      (BIS-11), Suicide Attitude Questionnaire (SAQ), Beck Hopelessness Scale (BHS),
      and Scale for Suicide Ideation (SSI)) were compared in the three groups. RESULTS:
      Compared with the healthy controls, all of the evaluated depressed patients
      showed increased functional connectivity in select DMN regions. The suicidal
      patients showed increased connectivity in the left cerebellum and decreased
      connectivity in the right posterior cingulate cortex (PCC), whereas the non
      suicidal depressed patients showed increased connectivity in the left superior
      frontal gyrus, left lingual gyrus and right precuneus and decreased connectivity
      in the left cerebellum. Compared to the non-suicidal patients, the suicidal
      patients showed increased connectivity in the left cerebellum and the left
      lingual gyrus and decreased connectivity in the right precuneus. No differences
      in the scores of any clinical scales were found between the suicidal and non
      suicidal depressed patients. CONCLUSIONS: Collectively, our results highlight the
      importance of the DMN in the pathophysiology of depression and suggest that
      suicidal behavior in depressed adolescents may be related to abnormal functional
      connectivity in the DMN. In particular, abnormal connectivity in the
      PCC/precuneus and left cerebellum might be a predictor of suicidal behavior in
      depressed adolescent patients.

PMID- 27688125
TI  - Opioid-Sparing Effect of Ketamine in Children: A Meta-Analysis and Trial
      Sequential Analysis of Published Studies.
AB  - INTRODUCTION: Reducing postoperative opioid consumption is a priority given its
      impact upon recovery, and the efficacy of ketamine as an opioid-sparing agent in
      children is debated. The goal of this study was to update a previous meta
      analysis on the postoperative opioid-sparing effect of ketamine, adding trial
      sequential analysis (TSA) and four new studies. MATERIALS AND METHODS: A
      comprehensive literature search was conducted to identify clinical trials that
      examined ketamine as a perioperative opioid-sparing agent in children and
      infants. Outcomes measured were postoperative opioid consumption to 48 h (primary
      outcome: postoperative opioid consumption to 24 h), postoperative pain intensity,
      postoperative nausea and vomiting and psychotomimetic symptoms. The data were
      combined to calculate the pooled mean difference, odds ratios or standard mean
      differences. In addition to this classical meta-analysis approach, a TSA was
      performed. RESULTS: Eleven articles were identified, with four added to seven
      from the previous meta-analysis. Ketamine did not exhibit a global postoperative
      opioid-sparing effect to 48 postoperative hours, nor did it decrease
      postoperative pain intensity. This result was confirmed using TSA, which found a
      lack of power to draw any conclusion regarding the primary outcome of this meta
      analysis (postoperative opioid consumption to 24 h). Ketamine did not increase
      the prevalence of either postoperative nausea and vomiting or psychotomimetic
      complications. CONCLUSIONS: This meta-analysis did not find a postoperative
      opioid-sparing effect of ketamine. According to the TSA, this negative result
      might involve a lack of power of this meta-analysis. Further studies are needed
      in order to assess the postoperative opioid-sparing effects of ketamine in
      children.

PMID- 27688128
TI  - Monitored anesthetic care and cataract surgery.

PMID- 27688129
TI  - Cervical spine anatomy and function for the anesthesiologist.

PMID- 27688126
TI  - Brain omega-3 polyunsaturated fatty acids modulate microglia cell number and
      morphology in response to intracerebroventricular amyloid-beta 1-40 in mice.
AB  - BACKGROUND: Neuroinflammation is a proposed mechanism by which Alzheimer's
      disease (AD) pathology potentiates neuronal death and cognitive decline.
      Consumption of omega-3 polyunsaturated fatty acids (PUFA) is associated with a
      decreased risk of AD in human observational studies and exerts protective effects
      on cognition and pathology in animal models. These fatty acids and molecules
      derived from them are known to have anti-inflammatory and pro-resolving
      properties, presenting a potential mechanism for these protective effects.
      METHODS: Here, we explore this mechanism using fat-1 transgenic mice and their
      wild type littermates weaned onto either a fish oil diet (high in n-3 PUFA) or a
      safflower oil diet (negligible n-3 PUFA). The fat-1 mouse carries a transgene
      that enables it to convert omega-6 to omega-3 PUFA. At 12 weeks of age, mice
      underwent intracerebroventricular (icv) infusion of amyloid-beta 1-40. Brains
      were collected between 1 and 28 days post-icv, and hippocampal microglia,
      astrocytes, and degenerating neurons were quantified by immunohistochemistry with
      epifluorescence microscopy, while microglia morphology was assessed with confocal
      microscopy and skeleton analysis. RESULTS: Fat-1 mice fed with the safflower oil
      diet and wild type mice fed with the fish oil diet had higher brain DHA in
      comparison with the wild type mice fed with the safflower oil diet. Relative to
      the wild type mice fed with the safflower oil diet, fat-1 mice exhibited a lower
      peak in the number of labelled microglia, wild type mice fed with fish oil had
      fewer degenerating neurons, and both exhibited alterations in microglia
      morphology at 10 days post-surgery. There were no differences in astrocyte number
      at any time point and no differences in the time course of microglia or astrocyte
      activation following infusion of amyloid-beta 1-40. CONCLUSIONS: Increasing brain
      DHA, through either dietary or transgenic means, decreases some elements of the
      inflammatory response to amyloid-beta in a mouse model of AD. This supports the
      hypothesis that omega-3 PUFA may be protective against AD by modulating the
      immune response to amyloid-beta.

PMID- 27688130
TI  - Lung isolation in thoracic anesthesia, state of the art.
AB  - Although the incidence of cases with the original indications for lung isolation
      such as abscess and hemoptysis has decreased, lung isolation is required with
      increasing frequency in an ever-widening spectrum of clinical situations. The
      preference of anesthesiologists has oscillated between bronchial blockers and
      single or double-lumen tubes for the past 50 yr. At present, double-lumen tubes
      continue to have the widest application for providing safe reliable lung
      separation in the majority of cases. However the optimal method of lung isolation
      in any individual case will depend on multiple factors which include the
      patient's underlying pathology and anatomy and the skill and training of the
      anesthesiologist.

PMID- 27688131
TI  - How much does it hurt? Pediatric pain measurement for doctors, nurses, and
      parents.

PMID- 27688132
TI  - The difficult pediatric airway - recognition, evaluation, and management.

PMID- 27688133
TI  - Postoperative pain management in patients with chronic pain syndromes.
AB  - The problems encountered when heavily medicated patients with chronic pain
      syndromes present for surgery are discussed in a case study. A management plan is
      proposed. The attending anesthesiologist, the acute and chronic pain service, the
      surgeon, the nursing staff, the patient and their significant others must be
      involved from the beginning.

PMID- 27688134
TI  - Trauma in pregnancy.
AB  - CONCLUSION: An exhaustive review of the care of the pregnant trauma patient would
      fill a book. Nevertheless, an understanding of the normal physiologic changes of
      pregnancy is virtually all there is to go on except in a few special situations
      such as listed above. Close communication with critical care, surgical and
      obstetrical colleagues are essential. This is certainly a clinical situation
      where a truly multi-disciplinary approach brings positive results. With this is
      mind it should be possible to confidently care for these special patients.

PMID- 27688135
TI  - Anesthesia and the progress of labour.
AB  - CONCLUSIONS: The last decade has seen a remarkable advance in our understanding
      of the effects of regional analgesia on the progress and outcome of labour. In
      particular, the appearance of several well conducted prospective, randomized
      trials have helped confirm the opinion of most anesthesiologists and a growing
      number of obstetricians, that epidural analgesia only minimally lengthens labour
      and does not increase the risk of cesarean section. But the extraordinary
      methodological complexities of studying this unblindable treatment in patients
      who are anything but ambivalent about whether or not they receive it ensures the
      debate will continue. It is perhaps time to move away from outcome studies and on
      to investigations of the putative mechanisms of any effects epidural analgesia
      may have on the labour and delivery process. It is also vital to place greater
      emphasis on the interaction between obstetrical practice, analgesic technique,
      and the patient. There may be important differences between subsets of patients
      with regard to their risk of cesarean section and the effect epidural analgesia
      may have on this risk. This is almost certainly true for certain obstetrical
      practices. Only by an appreciation of the actual physiology of epidural analgesia
      in the context of obstetrical care and the labour process itself will one of the
      longest running debates in anesthesiology come to an end.

PMID- 27688136
TI  - Regional anesthesia in ambulatory surgery.
AB  - Regional anesthesia is an attractive alternative for many ambulatory cases due to
      excellent postoperative pain relief and potential of speeding up the process from
      the OR to discharge. Regional anesthesia may be practised successfully in a busy
      ambulatory unit with a dedicated and simple regimen.

PMID- 27688137
TI  - Erythrocyte transfusion: friend or foe?

PMID- 27688138
TI  - Noninvasive ventilation in the ICU / La ventilation non invasive aux soins
      intensifs.
AB  - CONCLUSION: La ventilation non invasive est probablement un des progres majeurs
      des dix dernieres annees dans le traitement de l'insuffisance respiratoire aigue
      aux soins intensifs. Son efficacite a ete demontree dans plusieurs indications.
      Dans l'insuffisance respiratoire aigue hypercapnique, la VNI devrait constituer
      le traitement de premier choix. En evitant l'intubation endotracheale, la VNI
      permet de reduire de facon importante la morbidite infectieuse et non infectieuse
      associee a la ventilation mecanique, de meme que la mortalite dans certains
      groupes de patients. Comme il demeure toujours possible d'intuber le patient en
      cas d'echec, la VNI peut etre tentee dans plusieurs situations cliniques.
      Finalement, les succes de la VNI dependent de l'interet et de l'experience de
      l'equipe soignante.

PMID- 27688139
TI  - Current status of offpump coronary surgery (OPCAB).

PMID- 27688140
TI  - Gaining control: can we reduce perioperative cardiovascular complications?
AB  - Cardiovascular complications are common in patients at risk for coronary disease
      undergoing surgery. The role of hyperactivity of the sympathetic nervous system
      and impaired parasympathetic control mechanisms in the genesis and consequences
      of perioperative myocardial ischemia has been discussed. Sympathetic blocking
      drugs of the beta blocker and alpha2 agonist classes have been used extensively
      in the perioperative setting to control hemodynamic responses and reduce episodes
      of myocardial ischemia. To date, perioperative beta blockade is the only strategy
      shown to improve long-term outcome after surgery in this population.

PMID- 27688127
TI  - Learning fiberoptic intubation on a simple model transfers to the O.R.

PMID- 27688141
TI  - The catabolic response to surgery: how can it be modified by the
      anesthesiologist?
AB  - CONCLUSION: Despite profound advances in anesthesia care, feeding techniques, and
      drug development, the catabolic response to injury still represents a metabolic
      phenomenon in surgical patients, which deserves the attention of clinicians and
      researchers. Although there is evidence that single pharmacological interventions
      are able to modulate protein catabolism, nitrogen losses following surgery cannot
      be completely suppressed and organ function promptly restored. We believe that
      multimodal approaches combining analgesic, anesthetic and surgical strategies
      with the provision of specific nutrients and anabolic agents hold great promise
      for not only reducing the loss of body protein, but also for accelerating
      recovery, shortening the length of hospitalization, and reducing convalescence
      resulting in a major improvement in clinical outcome. Furthermore, the use of
      tracer methodologies will further increase our understanding of the
      pathophysiological changes induced by tissue trauma and will help to identify
      subgroups of patients who might particularly benefit from our therapeutical
      efforts.

PMID- 27688142
TI  - Neurologic complications of neuraxial and peripheral blockade.

PMID- 27688143
TI  - Effects of Karate Training Versus Mindfulness Training on Emotional Well-Being
      and Cognitive Performance in Later Life.
AB  - In a randomized controlled trial, we investigated the effects of karate versus a
      mindfulness-based stress reduction (MBSR) intervention on well-being and
      cognitive functioning in older adults. Fifty-five adults (52-81 years old)
      participated in twice-weekly karate versus MBSR sessions or no training for 8
      weeks. In pre- and postassessments, subjective well-being, health, cognitive
      functioning, and chronic stress were measured. Preassessment hair cortisol served
      as physiological stress marker. The results showed an improvement for the karate
      group, but not the MBSR and control group, in subjective mental health and
      anxiety as well as cognitive processing speed. The MBSR group showed by trend as
      a decrease in stress. No significant correlation between preassessment hair
      cortisol and postassessment outcomes could be established. But the higher the
      level of baseline self-reported perceived stress, the higher the increase in
      depression, anxiety, and chronic stress. Generally, it can be assumed that karate
      and MBSR showed only small training effects concerning the assessed emotional and
      cognitive parameters.

PMID- 27688147
TI  - Bleomycin-induced skin toxicity: is it always flagellate erythema?
AB  - Bleomycin-induced skin toxicity is a rare and unique complication. We report a 35
      year-old man with nodular lymphocytic predominant Hodgkin's lymphoma, stage IVB,
      who was started on adriamycin, bleomycin, vinblastin and dacarbazine (ABVD)
      chemotherapy. He developed pruritic hyperpigmented, patchy skin lesions on the
      neck, back, chest and thighs after IA cycle of ABVD chemotherapy. Lesions were
      not typical flagellate rash but hyperpigmented, patchy and mildly pruritic
      lesions over the trunk and proximal extremities. Lesions increased with
      continuation of bleomycin and improved gradually after removing the drug from
      chemotherapy schedule. The patient was in complete remission after VI cycles of
      chemotherapy (AVD Regimen) and skin lesions healed with minimal residual
      hyperpigmentation.

PMID- 27688144
TI  - Sex Disparities in Adverse Childhood Experiences and HIV/STIs: Mediation of
      Psychopathology and Sexual Behaviors.
AB  - HIV and other sexually transmitted infections (STIs) are important public health
      challenges in the US. Adverse childhood experiences (ACEs), including abuse
      (emotional, physical or sexual), witnessing violence among household members, may
      have an effect on sexual behaviors, which increase the risk of HIV/STIs. The aim
      of this study was to examine the sex differences in the role of posttraumatic
      stress disorder (PTSD), major depression (MD), substance use disorders (SUDs),
      early sexual debut, and intimate partner violence (IPV) perpetration as mediators
      in the association between ACEs and HIV/STIs. Data were obtained from Wave 2
      (2004-2005) of the National Epidemiologic Survey on Alcohol and Related
      Conditions. Structural equation modeling was used to determine the role of PTSD,
      MD, SUDs, early sexual debut, and IPV perpetration as mediators in the
      relationships between ACEs and HIV/STIs. Differences and similarities existed in
      the mediational roles of psychopathology and sexual behaviors. For example, among
      men, MD fully mediated physical/psychological abuse (beta = 0.0002; p = 0.012)
      and sexual abuse (beta = 0.0002; p = 0.006), and HIV/STIs while among women, MD
      fully mediated physical/psychological abuse (beta = 0.0005; p < 0.001) and
      parental violence (beta = -0.0002; p = 0.012). Among men, IPV perpetration fully
      mediated sexual abuse (beta = -0.0005; p = 0.012) and HIV/STIs while among women,
      IPV perpetration was not a statistically significant mediator. HIV/STI prevention
      and intervention programs should use a life course approach by addressing adverse
      childhood events among men and women and consider the sex differences in the
      roles of psychopathology and sexual behaviors.

PMID- 27688146
TI  - Assessment of diagnostic doses for widely used synthetic pyrethroids
      (Deltamethrin & Permethrin) in an endemic focus of leishmaniasis in Turkey.
AB  - BACKGROUND: Leishmania is a group of parasitic flagellated protozoons, which are
      transmitted by female sand flies and produces health problems in humans and also
      in wild and domestic animals. So far, 25 Phlebotomus and 4 Sergentomyia species
      were recorded in Turkey including proven or possible vectors of Leishmania spp.
      As no single insecticide susceptibility test was conducted targeting the sand
      flies in Turkey, we aimed to determine the diagnostic dose against two commonly
      used synthetic pyrethroids (deltamethrin and permethrin) in a hyperendemic area
      for leishmaniasis. METHODS: Sand flies were collected from villages of Adana in 2
      4 September 2013 using Centers for Disease Control and Prevention (CDC) light
      traps and transferred to the laboratory. The World Health Organisation tube test
      method was conducted using self-prepared filter papers with different
      concentrations. In order to determine the diagnostic dose, lethal doses (LD) were
      calculated by EPA Probit Analysis. Sand flies used in the experiments were
      dissected, mounted and identified. RESULTS: For the lowest (0.025 %) and highest
      dose of permethrin (0.5 %), the mortality rate was recorded as 52.6 % and 100 %
      by the end of 24-h period and the diagnostic dose was recorded as 0.36 %. The
      mortality rate for lowest (0.0025 %) and highest (0.05 %) doses of deltamethrin
      was recorded as 54.8 % and 100 %. The diagnostic dose of deltamethrin was
      determined as 0.9 %. CONCLUSION: An insecticide susceptibility study was
      conducted in Turkey for the first time and effective doses were determined by
      calculating the LDs. According to presented results, the wild population of sand
      flies collected from a hyper-endemic region of Adana Province is still
      susceptible to deltamethrin and permethrin.

PMID- 27688145
TI  - Large-scale characterization study of patients with antimitochondrial antibodies
      but nonestablished primary biliary cholangitis.
AB  - : The prevalence, clinical characteristics, and outcomes of patients with
      antimitochondrial antibodies (AMAs), but no clinical evidence of primary biliary
      cholangitis (PBC), are largely unknown. A prospective study of AMA incidence was
      conducted through a nation-wide network of 63 French immunology laboratories.
      Clinical data from 720 of 1,318 AMA-positive patients identified in 1 year were
      collected. Patients were categorized as either newly diagnosed with PBC (n =
      275), previously diagnosed with PBC (n = 216), or with nonestablished diagnosis
      of PBC (n = 229). The latter group was specifically evaluated. Follow-up data
      were collected for up to 7 years after detection of AMAs. Prevalence of AMA
      positive patients without evidence of PBC was 16.1 per 100,000. These patients
      had the following characteristics: 78% female; median age 58 years; median AMA
      titer 1:160; extrahepatic autoimmune disorders 46%; normal serum alkaline
      phosphatases (ALP) 74%; ALP above 1.5 times the upper limit of normal 13%; and
      cirrhosis 6%. Compared to those newly diagnosed with PBC, the patients were
      slightly younger, had lower AMA titers, and lower sex-ratio imbalance. Among the
      patients with normal ALP and no evidence of cirrhosis, the 5-year incidence rate
      of PBC was 16%. Whereas no patients died from PBC, the 5-year survival rate was
      75%, as compared to 90% in a control, standardized population matched for age and
      sex (P < 0.05). CONCLUSION: Nearly half of the newly detected AMAs in clinical
      practice does not lead to a diagnosis of PBC. PBC is unrecognized in 13% of those
      cases. Only 1 in 6 patients with AMAs and normal ALP will develop PBC after 5
      years. The mortality of AMA-positive patients without PBC is increased
      irrespective of the risk of PBC development. (Hepatology 2017;65:152-163).

PMID- 27688148
TI  - Severe accidental hypothermia treated with cardiopulmonary bypass.
AB  - This case report describes the successful treatment of severe accidental
      hypothermia with cardiopulmonary bypass (CPB). A known intravenous drug misuser
      aged 22 years was found to be unresponsive at his home (winter evening) with a
      Glasgow coma scale of 3/15. In the ambulance, the patient went into cardiac
      arrest, cardiopulmonary resuscitation being started. On arrival to the emergency
      department, he had a core body temperature of 27 degrees C which was refractory
      to conservative management. He underwent femoro-femoral CPB, which was successful
      in rewarming the patient slowly. The patient was discharged home with no
      neurological deficit 10 days later.

PMID- 27688149
TI  - Fused cervical vertebrae: a coincidental finding in a lateral cephalogram taken
      for orthodontic diagnostic purposes.

PMID- 27688150
TI  - The ACAT2 expression of human leukocytes is responsible for the excretion of
      lipoproteins containing cholesteryl/steryl esters.
AB  - Acyl-coenzymeA:cholesterol acyltransferase 2 (ACAT2) is abundantly expressed in
      intestine and fetal liver of healthy human. Our previous studies have shown that
      in monocytic cells the low-level expression of human ACAT2 gene with specific CpG
      hypomethylated promoter is regulated by the CCAAT/enhancer binding protein
      (C/EBP) transcription factors. In this study, we further report that the ACAT2
      gene expression is attributable to the C/EBPs in the human leukocytes and
      correlated with the excretion of fluorescent lipoproteins containing the ACAT2
      catalyzed NBD22-steryl esters. Moreover, this lipoprotein excretion can be
      inhibited by the ACAT2 isoform-selective inhibitor pyripyropene A (PPPA) in a
      dose-dependent manner, and employed to determine the half maximum inhibitory
      concentration (IC50) values of PPPA. Significantly, it is found that the
      differentiation-inducing factor all-trans retinoic acid, but not the
      proinflammatory cytokine tumor necrosis factor-alpha, enhances this ACAT2
      dependent lipoprotein excretion. These data demonstrate that the ACAT2 expression
      of human leukocytes is responsible for the excretion of lipoproteins containing
      cholesteryl/steryl esters (CE/SE), and suggest that the excretion of lipoproteins
      containing the ACAT2-catalyzed CS/SE may avoid cytotoxicity through decreasing
      the excess intracellular cholesterols/sterols (especially various oxysterols),
      which is essential for the action of the human leukocytes.

PMID- 27688152
TI  - A modelling tool for capacity planning in acute and community stroke services.
AB  - BACKGROUND: Mathematical capacity planning methods that can take account of
      variations in patient complexity, admission rates and delayed discharges have
      long been available, but their implementation in complex pathways such as stroke
      care remains limited. Instead simple average based estimates are commonplace.
      These methods often substantially underestimate capacity requirements. We analyse
      the capacity requirements for acute and community stroke services in a pathway
      with over 630 admissions per year. We sought to identify current capacity
      bottlenecks affecting patient flow, future capacity requirements in the presence
      of increased admissions, the impact of co-location and pooling of the acute and
      rehabilitation units and the impact of patient subgroups on capacity
      requirements. We contrast these results to the often used method of planning by
      average occupancy, often with arbitrary uplifts to cater for variability.
      METHODS: We developed a discrete-event simulation model using aggregate parameter
      values derived from routine administrative data on over 2000 anonymised admission
      and discharge timestamps. The model mimicked the flow of stroke, high risk TIA
      and complex neurological patients from admission to an acute ward through to
      community rehab and early supported discharge, and predicted the probability of
      admission delays. RESULTS: An increase from 10 to 14 acute beds reduces the
      number of patients experiencing a delay to the acute stroke unit from 1 in every
      7 to 1 in 50. Co-location of the acute and rehabilitation units and pooling eight
      beds out of a total bed stock of 26 reduce the number of delayed acute admissions
      to 1 in every 29 and the number of delayed rehabilitation admissions to 1 in
      every 20. Planning by average occupancy would resulted in delays for one in every
      five patients in the acute stroke unit. CONCLUSIONS: Planning by average
      occupancy fails to provide appropriate reserve capacity to manage the variations
      seen in stroke pathways to desired service levels. An appropriate uplift from the
      average cannot be based simply on occupancy figures. Our method draws on long
      available, intuitive, but underused mathematical techniques for capacity
      planning. Implementation via simulation at our study hospital provided valuable
      decision support for planners to assess future bed numbers and organisation of
      the acute and rehabilitation services.

PMID- 27688151
TI  - Low-level expression of human ACAT2 gene in monocytic cells is regulated by the
      C/EBP transcription factors.
AB  - Acyl-coenzyme A:cholesterol acyltransferases (ACATs) are the exclusive
      intracellular enzymes that catalyze the formation of cholesteryl/steryl esters
      (CE/SE). In our previous work, we found that the high-level expression of human
      ACAT2 gene with the CpG hypomethylation of its whole promoter was synergistically
      regulated by two transcription factors Cdx2 and HNF1alpha in the intestine and
      fetal liver. Here, we first observed that the specific CpG-hypomethylated
      promoter was correlated with the low expression of human ACAT2 gene in monocytic
      cell line THP-1. Then, two CCAAT/enhancer binding protein (C/EBP) elements within
      the activation domain in the specific CpG-hypomethylation promoter region were
      identified, and the expression of ACAT2 in THP-1 cells was evidently decreased
      when the C/EBP transcription factors were knock-downed using RNAi technology.
      Furthermore, ChIP assay confirmed that C/EBPs directly bind to their elements for
      low-level expression of human ACAT2 gene in THP-1 cells. Significantly, the
      increased expressions of ACAT2 and C/EBPs were also found in macrophages
      differentiated from both ATRA-treated THP-1 cells and cultured human blood
      monocytes. These results demonstrate that the low-level expression of human ACAT2
      gene with specific CpG-hypomethylated promoter is regulated by the C/EBP
      transcription factors in monocytic cells, and imply that the lowly expressed
      ACAT2 catalyzes the synthesis of certain CE/SE that are assembled into
      lipoproteins for the secretion.

PMID- 27688153
TI  - A three-dimensional alginate system for in vitro culture of cumulus-denuded
      feline oocytes.
AB  - In the case of high valuable individuals with very precious genetic material,
      widening the genetic pool including gametes with poor morphological
      characteristics, as cumulus-denuded oocytes (CDOs), could be an option. To
      improve the in vitro culture of low-competence feline CDOs, an enriched three
      dimensional (3D) system in association with competent cumulus-oocyte complexes
      (COCs) was developed. For this purpose, domestic cat CDOs were cultured with or
      without companion COCs in the 3D barium alginate microcapsules. The overall
      viability and the meiotic progression of feline CDOs cocultured with COCs or
      cultured separately in 3D or in 2D (traditional microdrops) system were compared.
      The 3D system was able to support viability and meiotic resumption of the feline
      oocytes, as well as the 2D microdrops. In 3D microcapsules, the presence of COCs
      resulted in a higher viability of CDOs (91.1%, p < .05), than that obtained
      without COCs or in 2D microdrops (71.2% and 67.3%, respectively), but the
      percentages of meiotic resumption were similar of those of CDOs cultured
      separately (55.4% vs. 40.4%, p > .05). It is notable that the presence of CDOs
      seemed to enhance the meiotic progression of the associated COCs. In conclusion,
      the 3D barium alginate microcapsules are a suitable system for feline oocytes in
      vitro culture, but more specific enriched conditions should be developed to
      improve the CDOs full competence in vitro.

PMID- 27688154
TI  - Multiplexed MRM-based assays for the quantitation of proteins in mouse plasma and
      heart tissue.
AB  - The mouse is the most commonly used laboratory animal, with more than 14 million
      mice being used for research each year in North America alone. The number and
      diversity of mouse models is increasing rapidly through genetic engineering
      strategies, but detailed characterization of these models is still challenging
      because most phenotypic information is derived from time-consuming histological
      and biochemical analyses. To expand the biochemists' toolkit, we generated a set
      of targeted proteomic assays for mouse plasma and heart tissue, utilizing bottom
      up LC/MRM-MS with isotope-labeled peptides as internal standards. Protein
      quantitation was performed using reverse standard curves, with LC-MS platform and
      curve performance evaluated by quality control standards. The assays comprising
      the final panel (101 peptides for 81 proteins in plasma; 227 peptides for 159
      proteins in heart tissue) have been rigorously developed under a fit-for-purpose
      approach and utilize stable-isotope labeled peptides for every analyte to provide
      high-quality, precise relative quantitation. In addition, the peptides have been
      tested to be interference-free and the assay is highly multiplexed, with
      reproducibly determined protein concentrations spanning >4 orders of magnitude.
      The developed assays have been used in a small pilot study to demonstrate their
      application to molecular phenotyping or biomarker discovery/verification studies.

PMID- 27688155
TI  - Sex and gender affect the social brain: Beyond simplicity.
AB  - As the most fascinating, complex, and dynamic part of our organism, the human
      brain is shaped by many interacting factors that not only are of neurobiological
      (including sex hormones) and environmental origin but are also sociocultural in
      their very nature (such as social roles). Gender is one of these factors. Most
      neurological, neurodevelopmental, neuropsychiatric, and psychosomatic disorders
      are characterized by impairments in visual social cognition (primarily body
      language reading and face perception) and a skewed sex ratio: females and males
      are affected differently in terms of clinical picture, prevalence, and severity.
      Is the social brain sex specific? This is still an open question. For a long time
      and for many reasons, sex differences have been overlooked or entirely ignored in
      neuroscience and biomedical research: there is a paucity of neuroimaging work
      examining sex differences in the social brain. However, the pattern of
      experimental behavioral data in both healthy, typically developing individuals
      and patients with deficient social cognition is beyond simple interpretation:
      contrary to popular wisdom, females are not always more proficient in
      understanding social signals, and their social abilities may be particularly
      affected by disease. Clarification of how neurobiological sex and sociocultural
      gender affect the social brain would provide novel insights into understanding
      gender-specific vulnerability to neuropsychiatric disorders. This interaction is
      far beyond simplicity. Although sex differences represent a rather delicate
      topic, underestimation or exaggeration of possible effects retards progress in
      the field. (c) 2016 Wiley Periodicals, Inc.

PMID- 27688156
TI  - Mesenchymal stem cells in the treatment of chronic lung disease.
AB  - Mesenchymal stem cells (MSCs) are a populace of non-haematopoietic multipotent
      stromal cells, which have the ability to differentiate into tissue derived from a
      single germ layer. MSCs have been isolated from various sites, including adipose
      tissue, skeletal muscle, synovium, spleen, thymus, lung and amniotic fluid, but
      are most often isolated from bone marrow. MSCs have several valuable functions
      that make them a promising therapeutic option in the field of regenerative
      medicine, including the secretion of anti-inflammatory cytokines and growth
      factors, the migration of cells to the site of injury when administered and the
      ability to 'rescue' cells through the transfer of functional mitochondria. They
      also offer the possibility of autologous cell transplantation, circumventing
      immune rejection. These properties, among others, make MSCs a promising potential
      therapeutic agent in the treatment of chronic lung diseases with high rates of
      morbidity and mortality, such as idiopathic pulmonary fibrosis (IPF), COPD and
      obstructive bronchiolitis (OB). Numerous animal models have shown the protective
      and reparative effects of MSCs in models of experimental lung injury. There are
      currently several clinical trials underway to evaluate the safety and efficacy of
      MSCs in the treatment of IPF, COPD and OB. While early results are encouraging, a
      considerable amount of research must be done concerning the safety MSCs, as well
      as their optimal dosage, time and route of administration. In addition, much is
      still unknown about the pathogenesis of these chronic lung diseases, as well as
      the mechanisms MSCs utilize to assist in their repair.

PMID- 27688157
TI  - Clinical spectrum and diagnostic pitfalls of multiple abnormal uptakes on bone
      scintigraphy.
AB  - Bone scintigraphy with technetium-99m (99mTc)-labeled diphosphonates is one of
      the most frequently performed radionuclide procedures. Accumulation of 99mTc
      labeled diphosphonate is well recognized to reflect conditions of accelerated
      bone turnover and metabolism. Therefore, it is a functional imaging modality for
      detecting metastatic bone tumors, metabolic bone disease, traumatic injury, and
      inflammation. This pictorial essay describes the possible patterns of
      distribution of abnormal uptake for differential diagnosis of metastatic bone
      tumor, as well as the diagnostic pitfalls of bone scintigraphy.

PMID- 27688158
TI  - Clinicopathological features and outcomes in patients with late recurrence of
      renal cell carcinoma after radical surgery.
AB  - OBJECTIVES: To characterize patients experiencing late recurrence after primary
      radical surgery for renal cell carcinoma and to approach the mechanism of late
      recurrence. METHODS: We retrospectively analyzed 657 consecutive patients who
      underwent radical surgery for pathologically confirmed <=stage III renal cell
      carcinoma in a single institution between January 1981 and December 2008. Early
      or late recurrence was defined as a recurrence occurring before or after 60
      months after primary surgery. RESULTS: Of 657 patients, 96 (14.6%) experienced
      early recurrence, and 41 (6.2%) developed late recurrence. Patients with late
      recurrence had smaller diameter of primary tumor (median 5 cm vs 8 cm, P <
      0.001), lower pathological stage (P < 0.001) and lower nuclear grade (P = 0.004)
      at primary surgery than those with early recurrence. On multivariate analysis,
      vascular invasion (including microscopic and gross invasion) was the predictor of
      late recurrence (P < 0.01, HR 3.79). Overall survival and disease-specific
      survival after recurrence were longer in patients with late recurrence (median 64
      and 76 months, respectively) than in those with early recurrence (34.5 and 35
      months, respectively; P = 0.008 and 0.002). CONCLUSIONS: These results suggest
      that micrometastasis at the time of surgery associated with vascular invasion at
      primary tumor site and their relatively lower malignant potential could lead to
      late recurrence. Further studies are warranted for better understanding and
      managing late recurrence of renal cell carcinoma.

PMID- 27688159
TI  - Safety and seizure control in patients with mesial temporal lobe epilepsy treated
      with regional superselective intra-arterial injection of autologous bone marrow
      mononuclear cells.
AB  - Temporal lobe epilepsy (TLE) is a highly prevalent syndrome among people with
      epilepsy, and is usually refractory to drug treatment. Structural and
      physiological changes, such as hippocampal sclerosis, are often present in TLE
      patients. The objective of this study is to evaluate the feasibility and safety
      of intra-arterial infusion of autologous bone marrow mononuclear cells (BMMC) in
      adults with medically refractory mesial TLE (MTLE) and unilateral hippocampal
      sclerosis (HS). We enrolled 20 patients who had been diagnosed with MTLE-HS and
      were refractory to medical treatment. All patients underwent a neurological
      evaluation, magnetic resonance imaging with hippocampal volumetry, video
      electroencephalography (EEG) with ictal recording, and a neuropsychological test
      battery focusing on verbal and nonverbal memory domains. After bone marrow
      aspiration and subsequent cell preparation, the BMMC were infused by selective
      posterior cerebral artery catheterization. Patients were followed for 6 months.
      Safety of the procedure, seizure frequency, neuropsychological evaluation, EEG
      variables, routine brain magnetic resonance imaging and hippocampal volumetry
      were considered measurements of outcome. Any serious intercurrent clinical event
      or adverse effects related to the procedure were reported. No additional lesions
      and no significant hippocampal volumetric changes were observed. EEG recordings
      showed a decrease in theta activity and spike density. At 6 months, eight
      patients (40%) were seizure free. A significant increase in the memory scores
      over time was observed. The BMMC autologous transplant for the treatment of
      temporal lobe epilepsy is feasible and safe. The seizure control achieved in this
      novel study supports the therapeutic potential of stem cell transplants in MTLE
      HS patients. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27688160
TI  - Effects of plantar stimulation on cardiovascular response to orthostatism.
AB  - PURPOSE: Walking is a complex locomotor process that involves both spinal cord
      reflexes and cortical integration of peripheral nerve input. Maintaining an
      upright body position requires not only neuromuscular activity but also
      cardiovascular regulation. We postulated that plantar mechanical stimulation
      might modulate autonomic nervous system activity and, thereby, impact blood
      pressure adaptation during standing. METHODS: Twelve healthy subjects underwent
      three randomly ordered 45-min 70 degrees -saddle tilt tests while the plantar
      surfaces of the feet were stimulated using specially engineered Korvit boots in
      the following modes: (1) no stimulation, (2) disrupted stimulation, and (3)
      walking mode. Orthostatic tolerance time was measured for each trial. During
      testing, we obtained an electrocardiogram and measured blood pressure, skin blood
      flow, and popliteal vein cross-sectional area. We estimated central hemodynamics,
      baroreflex sensitivity and heart rate variability. RESULTS: Orthostatic tolerance
      time was not found to differ significantly between test conditions (37.2 +/-
      10.4, 40.9 +/- 7.6, and 41.8 +/- 8.2 min, for no stimulation, disrupted
      stimulation, and walking mode, respectively). No significant differences between
      treatment groups were observed for stroke volume or cardiac baroreflex
      sensitivity, both of which decreased significantly from baseline during tilt
      testing in all groups. Cardiac sympathetic index and popliteal vein cross
      sectional area increased at the end of the tilt period in all groups, without
      significant differences between treatments. CONCLUSIONS: Plantar mechanical
      stimulation is insufficient for immediate modulation of cardiac sympathetic and
      parasympathetic activity under orthostatic stress.

PMID- 27688161
TI  - Prenatal Alcohol Exposure and Pair Feeding Differentially Impact Puberty and
      Reproductive Development in Female Rats: Role of the Kisspeptin System.
AB  - BACKGROUND: Reproductive maturation is initiated with the onset of puberty, which
      activates the hypothalamic-pituitary-gonadal axis and coincidences with increased
      expression of the hormone kisspeptin within the hypothalamus. Maturational events
      are sensitive to environmental factors, including alcohol, which is known to
      delay reproductive development. We hypothesized that, similar to alcohol's
      adverse effects during reproductive maturation, prenatal alcohol exposure (PAE)
      would alter pubertal markers, sex hormone profiles, and kisspeptin expression in
      the hypothalamus. METHODS: Female offspring from control (C), pair-fed (PF), and
      PAE groups were sacrificed prior to puberty onset (postnatal day [PND] 30),
      during puberty [PND 35], or in adulthood [PND 65]. Estradiol (E2 ), progesterone
      (P4 ), prolactin, and luteinizing hormone levels, and Kiss1 mRNA expression were
      measured in the arcuate (ARC) and anteroventral periventricular (AVPV) nuclei of
      the hypothalamus. Pubertal markers (vaginal opening [VO], uterus/body wt ratio)
      were assessed. RESULTS: Our findings indicate that (i) PAE inhibits the expected
      increases in E2 levels with age and delays maturational increases of P4 levels;
      (ii) PAE and pair feeding have similar adverse effects on VO and uterus/body wt
      ratio; (iii) differential relationships between PRL and P4 suggest that different
      mechanisms may underlie delayed maturation in PAE and PF; that is, PF females
      have low PRL levels and no increase in P4 with age, whereas PAE animals, despite
      low PRL, show the expected age-related increase in P4 ; and (iv) there is higher
      mean density of Kiss1 mRNA in the ARC of adult PAE females and altered Kiss1
      expression in the AVPV of both PAE and PF females. CONCLUSIONS: PAE and pair
      feeding have some overlapping but important differential effects on hormonal
      profiles and Kiss1 mRNA expression during reproductive development. Preadolescent
      alterations in Kiss1 expression in the AVPV and ARC, which may change the balance
      of function in these 2 nuclei, may differentially contribute to delayed
      reproductive maturation in PAE and PF compared to C females.

PMID- 27688162
TI  - Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy
      with fusions of dendritic and glioma cells in patients with glioblastoma.
AB  - BACKGROUND: This trial was designed to evaluate the safety and clinical responses
      to a combination of temozolomide (TMZ) chemotherapy and immunotherapy with
      fusions of DCs and glioma cells in patients with glioblastoma (GBM). METHOD: GBM
      patients were assigned to two groups: a group of recurrent GBMs after failing TMZ
      chemotherapy against the initially diagnosed glioma (Group-R) or a group of newly
      diagnosed GBMs (Group-N). Autologous cultured glioma cells obtained from surgical
      specimens were fused with autologous DCs using polyethylene glycol. The fusion
      cells (FC) were inoculated intradermally in the cervical region. Toxicity,
      progression-free survival (PFS), and overall survival (OS) of this trial were
      evaluated. Expressions of WT-1, gp-100, and MAGE-A3, recognized as
      chemoresistance-associated peptides (CAP), were confirmed by immunohistochemistry
      of paraffin-embedded tumor samples. Patient's PBMCs of pre- and post-vaccination
      were evaluated by tetramer and ELISPOT assays. RESULTS: FC-immunotherapy was well
      tolerated in all patients. Medians of PFS and OS of Group-R (n = 10) were 10.3
      and 18.0 months, and those of Group-N (n = 22) were 18.3 and 30.5 months,
      respectively. Up-regulation and/or cytoplasmic accumulation of CAPs was observed
      in the recurrent tumors of Group-R patients compared with their initially excised
      tumors. Specific immune responses against CAPs were observed in the tetramer and
      ELISPOT assays. CONCLUSIONS: The combination of TMZ-treatment leading to up
      regulation and/or cytoplasmic accumulation of CAPs, with FC-immunotherapy as a
      means of producing specific immunity against CAPs, may safely induce anti-tumor
      effects in patients with GBM.

PMID- 27688163
TI  - Predicting PD-L1 expression on human cancer cells using next-generation
      sequencing information in computational simulation models.
AB  - PURPOSE: Interaction of the programmed death-1 (PD-1) co-receptor on T cells with
      the programmed death-ligand 1 (PD-L1) on tumor cells can lead to
      immunosuppression, a key event in the pathogenesis of many tumors. Thus,
      determining the amount of PD-L1 in tumors by immunohistochemistry (IHC) is
      important as both a diagnostic aid and a clinical predictor of immunotherapy
      treatment success. Because IHC reactivity can vary, we developed computational
      simulation models to accurately predict PD-L1 expression as a complementary assay
      to affirm IHC reactivity. METHODS: Multiple myeloma (MM) and oral squamous cell
      carcinoma (SCC) cell lines were modeled as examples of our approach. Non
      transformed cell models were first simulated to establish non-tumorigenic control
      baselines. Cell line genomic aberration profiles, from next-generation sequencing
      (NGS) information for MM.1S, U266B1, SCC4, SCC15, and SCC25 cell lines, were
      introduced into the workflow to create cancer cell line-specific simulation
      models. Percentage changes of PD-L1 expression with respect to control baselines
      were determined and verified against observed PD-L1 expression by ELISA, IHC, and
      flow cytometry on the same cells grown in culture. RESULT: The observed PD-L1
      expression matched the predicted PD-L1 expression for MM.1S, U266B1, SCC4, SCC15,
      and SCC25 cell lines and clearly demonstrated that cell genomics play an integral
      role by influencing cell signaling and downstream effects on PD-L1 expression.
      CONCLUSION: This concept can easily be extended to cancer patient cells where an
      accurate method to predict PD-L1 expression would affirm IHC results and improve
      its potential as a biomarker and a clinical predictor of treatment success.

PMID- 27688165
TI  - Upregulation of SIRT1-AMPK by thymoquinone in hepatic stellate cells ameliorates
      liver injury.
AB  - Thymoquinone (TQ) is a biologically active compound isolated from the seeds of
      Nigella sativa L. (Ranuculaceae). This study investigated the hepato-protective
      effect of TQ on liver injury through AMP-activated protein kinase (AMPK)
      signaling in hepatic stellate cells (HSCs). In vitro, TGF-beta time-dependently
      attenuated liver kinase B-1 (LKB1) and AMPK phosphorylation, which were blocked
      by pretreatment with TQ and AICAR (an activator of AMPK). TQ significantly
      inhibited collagen-Iota, alpha-SMA, TIMP-1 and enhanced MMP-13 expression,
      contributing to prevent TGF-beta-induced human HSCs activation. Moreover, TQ
      induced peroxisome proliferator activated receptor-gamma (PPAR-gamma) expression,
      which was inhibited by genetic deletion of AMPK. In vivo, C57BL/6 mice were fed
      with ethanol diet for 10 days, then administering a single dose of ethanol (5g/kg
      body weight) via gavage. TQ (20 or 40mg/kg) were given by gavage every day. TQ
      attenuated the increases in serum aminotransferase and hepatic triglyceride in
      mice fed with ethanol, while significantly activated LKB1 and AMPK
      phosphorylation. In addition, TQ enhanced the sirtuin 1 (SIRT1) expression. In
      conclusion, we demonstrate that AMPK pathway is a key therapeutic target for
      controlling liver injury and TQ confers hepato-protection against TGF-beta
      induced the activation of HSCs and ethanol-induced liver injury.

PMID- 27688166
TI  - Randomised trial of bisphosphonate-coated dental implants: Radiographic follow-up
      after five years of loading.
AB  - The results of a randomised trial with bisphosphonate-coated dental implants have
      been reported previously. Each patient received one coated and one uncoated
      implant in a double-blind split-mouth design study. After 6 months of
      osseointegration, resonance frequency analysis indicated better fixation of the
      coated implants. Reduced marginal bone resorption was also shown. However, it was
      not known whether the advantage of the bisphosphonate coating would persist over
      time. The radiographic results at 5 years after implant installation are reported
      herein. A blinded investigator measured marginal resorption on fresh radiographs
      obtained for 14 of the 16 patients (two had died) and compared these with the
      post-implantation images. Non-parametric statistics were used. All implants
      functioned well. The median marginal bone loss for control implants was found to
      be 0.70mm, which is less than usually reported in the literature. The
      bisphosphonate-coated implants showed even less resorption (median 0.20mm). The
      median difference within each pair of implants after 5 years of use was 0.34mm
      (95% confidence interval 0.00-0.75mm; P=0.04). The present data suggest that
      bisphosphonate-coated implants enable prolonged preservation of the marginal
      bone.

PMID- 27688164
TI  - A Psycho-Educational Intervention for People with a Family History of Depression:
      Pilot Results.
AB  - We developed and pilot-tested the first online psycho-educational intervention
      that specifically targets people with a family history of depression ('LINKS').
      LINKS provides genetic risk information and evidence-rated information on
      preventive strategies for depression and incorporates a risk assessment tool and
      several videos using professional actors. LINKS was pilot-tested in the general
      practitioner (GP) setting. The patient sample included people with a family
      history of at least one first-degree relative (FDR) with major depressive
      disorder (MDD) or bipolar disorder (BD). Patients attending participating GP
      practices were invited to enroll in the study by letter from their GP. Patients
      who self-identified as having at least one first-degree relative (FDR) with MDD
      or BD were eligible. Patients completed questionnaires, pre-post viewing LINKS,
      with measures assessing satisfaction, relevance, emotional impact and perceived
      improvement of understanding. Six GP practices participated, and 24 patients
      completed both questionnaires. Of these, all reported that they were satisfied or
      very satisfied with LINKS, and 74 % reported that LINKS met their expectations,
      and 21 % that it exceeded their expectations. LINKS was judged highly acceptable
      by this sample of GP attendees, and results indicate that an assessment of its
      effectiveness in a larger controlled trial is warranted.

PMID- 27688167
TI  - Changes in the lower lip soft tissue after bone graft harvesting from the
      mandibular symphysis.
AB  - Following the surgical release of the mentalis muscle, lip incompetence and/or an
      increase in lower incisor exposure may be seen due to undesirable attachment of
      the muscle fibres. The aim of this study was to evaluate the extent of lip
      ptosis, lower incisor exposure, and other soft tissue changes following bone
      graft harvesting from the mandibular symphysis when the mentalis muscle is
      reapproximated precisely to its original position. Seventeen consecutive patients
      who underwent bone graft harvesting from the mandibular symphysis were included
      in this study. The mentalis muscle was isolated, identified, marked, and
      reapproximated precisely during the bone harvesting operation. Digital lateral
      cephalograms obtained preoperatively and at 6 months postoperative were analyzed
      and compared by paired samples t-test to determine the horizontal and vertical
      soft tissue changes in the lower lip and chin. Although the soft tissue thickness
      at soft tissue point B and at soft tissue pogonion had increased significantly at
      6 months after chin bone graft harvesting, there were no significant changes in
      lower incisor exposure or other positional alterations of the lower lip (P<0.05).
      Precise reattachment of the mentalis muscle in its original position helps to
      avoid significant vertical positional changes in the lower lip. Increases in soft
      tissue thickness can be observed following bone graft harvesting from the
      mandibular symphysis.

PMID- 27688168
TI  - Effects of surgical correction of class III malocclusion on the pharyngeal airway
      and its influence on sleep apnoea.
AB  - The objective of this study was to evaluate, through cone beam computed
      tomography, the immediate changes in pharyngeal airway space (PAS) after
      orthognathic surgery in class III patients, and to determine the influence of
      surgery on the development of obstructive sleep apnoea hypopnoea syndrome
      (OSAHS). A prospective study was conducted; 33 patients were divided into three
      groups: mandibular setback surgery (nine patients), bimaxillary surgery (18
      patients), and maxillary advancement surgery (six patients). PAS measurements
      obtained pre- and postoperatively were compared using the t-test. All patients
      were assessed clinically for OSAHS before surgery and at 6 months postoperative
      using the Berlin questionnaire and a combined clinical assessment, which included
      the assessment of OSAHS symptoms, Epworth Sleepiness Scale score, and body mass
      index. Patients undergoing isolated mandibular setback surgery demonstrated a
      decrease in total PAS volume, in hypopharynx volume, and in minimum cross
      sectional area of the pharynx immediately after surgery (P<0.05). The clinical
      analysis did not reveal signs or symptoms of OSAHS in any of the 33 patients.
      Although patients who underwent mandibular setback surgery alone demonstrated a
      volume reduction in the PAS and a decrease in minimum cross-sectional area, these
      reductions were not accompanied by signs or symptoms of OSAHS.

PMID- 27688169
TI  - The influence of mild dysplasia at the surgical margin on the prognosis of oral
      squamous cell carcinoma.
AB  - The purpose of this study was to evaluate the clinical relevance between
      different margin statuses and local recurrence rate in patients undergoing
      primary surgical treatment for oral squamous cell carcinoma (OSCC). Five hundred
      and thirty-nine patients with T1-4N0M0 OSCC, who underwent surgery alone at a
      stomatology hospital in Nanjing, China during the years 2005-2014, were included.
      Tumour and margin status were assessed. Overall survival (OS), disease-free
      survival (DFS), and recurrence-free survival (RFS) were calculated by Kaplan
      Meier method. Predictors of RFS, OS, and DFS were analysed. Positive or
      dysplastic margins were found in the initial specimen in 20.0% of the cases. On
      multivariate analysis, there was no significant difference between RFS (hazard
      ratio (HR) 1.379, P=0.361) or DFS (HR 1.452, P=0.183) of those with mild
      dysplasia and those with negative margins. However, patients with mild dysplasia
      who did not undergo re-excision demonstrated significantly worse RFS (HR 2.286,
      P=0.010) and DFS (HR 2.070, P=0.014) than those with negative margins. It is
      concluded that there appears to be a correlation between initial mild dysplastic
      margins that are not subjected to re-excision and inferior RFS and DFS.
      Additional attention should be drawn to mild dysplasia at the initial margin in
      OSCC, and extended excision is suggested.

PMID- 27688170
TI  - Late mandibular fracture occurring in the postoperative period after third molar
      removal: systematic review and analysis of 124 cases.
AB  - Factors associated with the diagnosis, aetiology, and treatment of mandibular
      fractures occurring during the postoperative period following the removal of a
      lower third molar are discussed. The following databases were searched using
      specific key words: PubMed/MEDLINE, LILACS, Embase, and Scopus. The search
      yielded 124 cases. Sex, age, side, tooth position and angulation, bone impaction,
      relationship between the tooth and the inferior alveolar nerve, local
      pathological conditions, aetiology of the fracture, symptomatology, and time
      between surgery and fracture, as well as any displacement of the fracture and the
      treatment of the fracture, were evaluated. Data were tabulated and the chi2
      statistical test was applied (P<0.05). Male patients aged >35 years, with teeth
      in positions II/III and B/C, complete bony impaction, and local bone-like
      alterations, were found to have a higher frequency of fracture and pericoronitis
      (P<0.05). Late fractures generally occurred between the second and fourth
      postoperative weeks (P<0.05). They were generally not displaced and the typical
      treatment was the non-surgical approach (P<0.05). It is concluded that the risk
      of mandibular fracture after extraction is associated with excessive ostectomy
      and/or local alterations. At-risk patients should be thoroughly briefed on the
      importance of a proper postoperative diet.

PMID- 27688171
TI  - A rapid and fully automatic method for the accurate determination of a wide
      carbon-chain range of per- and polyfluoroalkyl substances (C4-C18) in human
      serum.
AB  - A rapid and fully automatic method for determining 21 per- and polyfluoroalkyl
      substances (with carbon chains ranging from C4 to C18, including 13 PFCAs, 5
      PFSAs, 2 Cl-PFESAs, and PFOSA) in human serum samples was developed. The HPLC
      parameters, Turboflow column, mobile phase, sample injection volume, loading flow
      rate, and sample cleanup and elution time were optimized. 25MUL serum sample was
      directly injected into the developed on-line Turboflow SPE HPLC-MS/MS system for
      analysis after dilution. Matrix effects were corrected due to the matrix removal
      efficiency of the Turboflow column and sufficient types of internal isotope
      standards that were used. The established method showed a good linearity
      (r2>0.99), rapid processing time (20min per sample), satisfactory recoveries
      (matrix spiked recoveries range from 84.6% to 114%) and precision (intra-day and
      inter-day RSDs ranged from 1.5% to 9.2% and from 1.1% to 7.0%, respectively). The
      limits of detection (LODs) of the 21 analyzed PFASs were between 0.008 and
      0.19ngmL-1. The LODs of short- and long-chain PFASs, such as PFBA, PFPeA, PFHxDA,
      and PFODA, were 0.008, 0.022, 0.15 and 0.19ngmL-1, respectively; the spiked
      recoveries of these PFASs were 101, 105, 87.1, and 85.8%, respectively. Both the
      LODs and recoveries were better than previous studies. Further, serum PFASs
      concentrations detected by the presented on-line SPE method were consistent with
      the traditional off-line SPE method (r: 0.98-0.99), which verified the accuracy
      and applicability of the present method. The method shows good practical
      prospects in the analysis of trace per- and polyfluoroalkyl substances in human
      serum.

PMID- 27688172
TI  - Using a box instead of a column for process chromatography.
AB  - Columns with relatively short bed-height to diameter ratios are frequently used
      for process-scale chromatography applications such as biopharmaceutical
      purification. Non-uniform flow distribution within such columns could result in
      broad and poorly resolved eluted peaks, which could in turn affect purity,
      recovery and productivity of the process. Different strategies centered on
      improved column header design have been proposed for addressing this problem.
      This paper describes a radically different approach, i.e. the use of a
      chromatography box (or chromato-box) instead of a column, for addressing the
      challenges posed by flow mal-distribution in process-scale, packed-bed
      chromatography devices. The design of the chromatography box devices used in this
      study is based on a laterally-fed membrane chromatography (or LFMC) device, that
      has been described and discussed in several recent papers. The performances of
      two chromatography box devices were compared with their equivalent columns in
      terms of sharpness and asymmetry of flow-through and eluted peaks, number of
      theoretical plates per metre, and peak resolution in binary and ternary protein
      separations. In each of the above comparisons, the chromatography box devices
      performed better than their equivalent columns, clearly indicating their
      potential as an alternative in process-scale chromatography applications.

PMID- 27688173
TI  - Determination of glucose in human stomach cancer cell extracts and single cells
      by capillary electrophoresis with a micro-biosensor.
AB  - Bioactive species in cells can provide information about signal transduction,
      cell function, and the effects of disease treatment. In this article, a novel
      micro-biosensor was fabricated to detect glucose in individual human stomach
      cancer cells (MGC80-3 cells) with capillary electrophoresis (CE). We fabricated
      the micro-biosensors by immobilizing a single-walled carbon nanotube-glucose
      oxidase (GOx)-glutaraldehyde (GA) bio-composite at the palladium nanoparticle
      (PdNPs) modified Pt electrode. The linear concentration of glucose ranged from
      2.0MUM to 1.0mM, with a detection limit of 0.5MUM. Using this method, the mean
      amount of glucose in MGC80-3 cell extracts and in single cells was 20.0 fmol and
      20+/-6 fmol (n=10), respectively. The micro-biosensor exhibited high sensitivity,
      stability, and a long operating life, which are likely due to the biocompatible
      environment provided by BSA and GA, and the adsorption and faster electron
      transfer of SWNTs and PdNPs to GOx.

PMID- 27688174
TI  - Preparation and characterization of magnetic molecularly imprinted polymers for
      selective trace extraction of dienestrol in seawater.
AB  - Highly selective and efficient magnetic molecularly imprinted polymers (MMIPs)
      were prepared using Fe3O4@SiO2 as a magnetic supporter, 3
      methacryloxypropyltrimethoxy-silane (MPS) as a silane coupling agent, DIS as a
      template, methacrylic acid (MAA) as a functional monomer and ethyleneglycol
      dimethacrylate (EGDMA) as a cross-linker for the extraction of trace residuals of
      the synthetic estrogen dienestrol (DIS) in seawater, which is a concern worldwide
      for its endocrine disruption and carcinogenic danger to human health. The
      obtained MMIPs were demonstrated to have spherical morphologies, core-shell
      structures, large binding capacities, high efficiency and selectivity. These were
      characterized by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and adsorption experiments. Owing to the specific binding sites,
      the MMIPs exhibited an almost three times higher adsorption capacity towards DIS
      (Qmax=4.68mgg-1) than magnetic molecularly non-imprinted polymers (MNIPs)
      (Qmax=1.72mgg-1). DIS in spiked seawater samples from the Weihai Bay of China was
      extracted and enriched by MMIPs, and satisfactory recoveries (87.3%-96.4%) with
      low relative standard deviation (RSD) values (2.03%-5.18%, n=5) were obtained.
      The limit of detection (LOD) of the method obtained was 0.16MUgL-1, and the limit
      of quantitation was 0.52MUgL-1 after MMIPs. No significant deterioration of the
      adsorption capacity of the MMIPs was observed after six rounds of regeneration.
      The results further demonstrated the applicability of the MMIPs method, a simple
      and straightforward method for the extraction and enrichment of DIS in seawater
      without any time-consuming procedures.

PMID- 27688175
TI  - Multiple, simultaneous, independent gradients for a versatile multidimensional
      liquid chromatography. Part II: Application 1 - Large increases in isoform
      resolution of human transferrin by use of dual simultaneous independent gradients
      of pH & acetonitrile on a mixed bed (anion exchange plus reversed phase)
      stationary phase.
AB  - We have previously described a liquid chromatographic (LC) method for uncoupling
      controlled, wide range pH gradients and simultaneous controlled gradients of a
      non-buffering solute on ion exchange resins (Hirsh and Tsonev, 2012) [1]. Here we
      report the application of this two dimensional LC technique to the problem of
      resolving Human Transferrin (HT) isoforms. This important iron transporting
      protein should theoretically occur in several thousand glycoforms, but only about
      a dozen have been reported. Using dual simultaneous independent gradients (DSIGs)
      of acetonitrile (ACN) and pH on a mixed bed stationary phase (SP) consisting of a
      mixture of an anion exchange resin and a reversed phase (RP) resin we partially
      resolve about 60 isoforms. These are likely to be partially refolded glycoforms
      generated by interaction of HT with the highly hydrophobic RP SP, as well as
      distinct folded glycoforms. Thus this study should have interesting implications
      for both glycoform separation and the study of protein folding.

PMID- 27688176
TI  - Innovative analysis of 3-mercaptohexan-1-ol, 3-mercaptohexylacetate and their
      corresponding disulfides in wine by stable isotope dilution assay and nano-liquid
      chromatography tandem mass spectrometry.
AB  - Both 3-mercaptohexan-1-ol (3MH) and 3-mercaptohexyl acetate (3MHA) were largely
      studied for the last 20 years due to their pleasant olfactory notes conferred to
      wine. Until now, many analytical methods focused only on the free forms of both
      3MH and 3MHA in wine that provided partial information in the wine aroma
      evolution. Our study proposes new analytical measurements which allow
      quantification of both free and disulfide forms of 3MH and 3MHA to better
      understand the redox phenomenon occurring in wines and further, to orientate wine
      aroma evolution. Free thiols were analyzed by an original method based on
      maleimide derivatization allowing in-situ disulfide reduction followed by SIDA-LC
      MS/MS analyses exhibiting excellent performances. Indeed, the accuracy ranged
      from 95 to 110% in three different wine matrices and the repeatability and
      intermediate reproducibility were inferior to 15% (RSD measurements). Our method
      exhibited very low limits of detection, which are below to 0.5ng/L and inferior
      to the perception thresholds of both compounds. Then, this method was applied to
      three different wines exposed to several oxidative conditions. On the one hand,
      it was demonstrated that copper sulfate treatment firstly destroyed the total
      amount of free 3MH to the benefit of thioether and disulfides compounds, with
      proportions that could be slightly modified by glutathione addition. On the other
      hand, oxygenation of wines resulted in partial free 3MH destruction to the
      benefit of thioether compounds. We proposed for the first time an innovative
      analysis that gives a complete picture of wine aroma, which can be really useful
      to winemakers to manage wine aroma evolution and to take advantage of the
      disulfide reservoir.

PMID- 27688177
TI  - Highly porous nanostructured copper foam fiber impregnated with an organic
      solvent for headspace liquid-phase microextraction.
AB  - A new headspace liquid-phase microextraction technique based on using a copper
      foam nanostructure substrate followed by gas chromatography-flame ionization
      detection was developed for the determination of volatile organic compounds in
      water and wastewater samples. The copper foam with highly porous nanostructured
      walls was fabricated on the surface of a copper wire by a rapid and facile
      electrochemical process and used as the extractant solvent holder. Propyl
      benzoate was immobilized in the pores of the copper foam coating and used for the
      microextraction of benzene, toluene, ethylbenzene and xylenes. The experimental
      parameters such as the type of organic solvent, desorption temperature,
      desorption time, salt concentration, sample temperature, equilibrium time and
      extraction time, were investigated and optimized. Under the optimum conditions,
      the method detection limit was between 0.06 and 0.25MUgL-1. The relative standard
      deviation of the method for the analytes at 4-8MUgL-1 concentration level ranged
      from 7.9 to 11%. The fiber-to-fiber reproducibility for three fibers prepared
      under the same condition was 9.3-12%. The enrichment factor was in the range of
      615-744. Different water samples were analyzed for the evaluation of the method
      in real sample analysis. Relative recoveries for spiked tap, river and wastewater
      samples were in the range of 85-94%. Finally, the extraction efficiency of the
      method was compared with those of headspace single drop microextraction and
      headspace SPME with the commercial fibers.

PMID- 27688178
TI  - Establishment of rock bream Oplegnathus fasciatus embryo (RoBE-4) cells with
      cytolytic infection of red seabream iridovirus (RSIV).
AB  - Red seabream iridovirus (RSIV) is a member of genus Megalocytivirus in the family
      Iridoviridae. RSIV infection causes significant economic losses of marine-fishes
      in East Asian countries. Grunt fin (GF) cell line has been commonly used for
      culturing RSIV. However, it is not suitable for definite evaluation of
      infectivity titer of RSIV because cells infected with RSIV are not completely
      cytolysed. Thus, we established a new cell line, RoBE-4, from rock bream
      (Oplegnathus fasciatus) eyed-egg embryos in this study. Morphologically, RoBE-4
      cells were fibroblastic-like. They have been stably grown over two-years with 60
      passages using Leibovitz's L-15 medium containing 10% (v/v) fetal bovine serum.
      RoBE-4 cells infected with RSIV exhibited cytopathic effects (CPE) with cell
      rounding. They were cytolysed completely after >=2 weeks of culture. Numerous
      RSIV particles with icosahedral morphology of approximately 122nm in diameter
      were observed in cytoplasmic area of infected RoBE-4 cells. The RSIV
      suceptibility and amount of extracellular RSIV released by RoBE-4 cells were 100
      fold higher than those by GF cells. RSIV cultured with RoBE-4 cells was highly
      virulent to rock bream in infection experiments. Therefore, using RoBE-4 cells
      instead of GF cells will enable accurate and sensitive measurement of RSIV
      infectivity. In addition, RoBE-4 cells might be used to produce RSIV vaccine in
      the future with significant reduction in cost.

PMID- 27688180
TI  - Design and discovery of 4-anilinoquinazoline-urea derivatives as dual TK
      inhibitors of EGFR and VEGFR-2.
AB  - EGFR and VEGFR-2 are involved in pathological disorders and the progression of
      different kinds of tumors, the combined blockade of EGFR and VEGFR signaling
      pathways appears to be an attractive approach to cancer therapy. In this work, a
      series of 4-anilinoquinazoline derivatives containing substituted diaryl urea or
      glycine methyl ester moiety were designed and identified as EGFR and VEGFR-2 dual
      inhibitors. Compounds 19i, 19j and 19l exhibited the most potent inhibitory
      activities against EGFR (IC50 = 1 nM, 78 nM and 51 nM, respectively) and VEGFR-2
      (IC50 = 79 nM, 14 nM and 14 nM, respectively), they showed good antiproliferative
      activities as well. Molecular docking established the interaction of 19i with the
      DFG-out conformation of VEGFR-2, suggesting that they might be type II kinase
      inhibitors.

PMID- 27688179
TI  - Evisceration surgery in a highly specialized center in Mexico: A retrospective
      study of 7 years of experience.
AB  - INTRODUCTION: Evisceration is currently becoming the technique of choice in the
      treatment of certain eye diseases, including, among others, painful blind eye and
      endophthalmitis. The most widely used implants are currently the hydroxyapatite
      and porous polyethylene for the rehabilitation of the anophthalmic socket.
      OBJECTIVE: To describe the indications, type of implant material used, and
      complications in evisceration surgery. METHODS: A retrospective, observational,
      descriptive study based on clinical records of patients that underwent
      evisceration between 2008 and 2015 in the Instituto Fundacion Conde de
      Valenciana, Mexico. RESULTS: A total of 186 evisceration surgeries were
      performed, of which 52.7% of the patients were men. The mean age was 54 years.
      The right eye was eviscerated in 53% of cases, and 79.2% had a vision of no light
      perception. Most patients had preoperative pain. The most common diagnosis for
      which evisceration was performed was endophthalmitis. Phthisis bulbi was reported
      in 20 eyes. A primary implant was inserted in 86.81% of the cases, with 34.81% of
      the implants being made of porous polyethylene. Four cases showed extrusion of
      the implant, with 2 cases of porous polyethylene. The ocular prosthesis was
      tolerated in 91% of cases. There were no cases of sympathetic ophthalmia.
      CONCLUSION: Evisceration is shown to be a good alternative to enucleation in
      cases where the sclera can be preserved, showing a low incidence of sympathetic
      ophthalmia.

PMID- 27688182
TI  - 4-Aminoquinoline-ferrocenyl-chalcone conjugates: Synthesis and anti-plasmodial
      evaluation.
AB  - A series of aliphatic and aromatic substituted 1H-1,2,3-triazole-tethered 4-amino
      quinoline-ferrocenylchalcone conjugates has been synthesized and evaluated for
      anti-plasmodial activity. The conjugates with flexible aliphatic (aminoethanol or
      aminopropanol) substituents on the quinoline ring showed better anti-plasmodial
      activities compared to those with cyclic (piperazine or aminophenol)
      substituents. The conjugate 17j was the most potent and non-cytotoxic, with an
      IC50 value of 0.37 MUM against the chloroquine-resistant W2 strain of Plasmodium
      falciparum.

PMID- 27688181
TI  - Synthesis and evaluation of C9 alkoxy analogues of (-)-stepholidine as dopamine
      receptor ligands.
AB  - Tetrahydroprotoberberine alkaloids have shown interesting polypharmacological
      actions at dopamine receptors and are a unique template from which to mine novel
      molecules with dual selective actions at D1 and D3 receptors. Such compounds will
      be valuable to evaluate as anti-cocaine therapeutics. Towards that eventual goal,
      we engaged an SAR study in which a series of C9 alkoxy analogues of the D1/D2/D3
      ligand (-)-stepholidine that possessed or lacked a C12 bromo functionality, were
      synthesized and evaluated for affinity at dopamine D1, D2 and D3 receptors. We
      found that the analogues are generally selective for the D1 receptor. Small n
      alkoxy substituents (up to 4 carbons in length) were generally well tolerated for
      high D1 affinity but such groups reduced D3 affinity. In the case of C12
      brominated analogues, C9 alkoxylation also had little effect on D1 affinity for
      the smaller alkoxy groups, but reduced D2 and D3 affinities significantly. C12
      bromination tends to increase D1 receptor selectivity. A number of compounds were
      identified that retain affinity for D1 and D3 receptors but lack D2 receptor
      affinity. Among them, compound 22a was found to be a selective D1/D3 dual
      antagonist (Ki = 5.3 and 106 nM at D1 and D3 receptors). Docking studies
      performed on the analogues at the D3 receptor revealed a number of interactions
      that are important for affinity including a critical N - Asp110 salt bridge
      motif, H-bonds to Ser192 and Cys181 and hydrophobic interactions between the aryl
      rings and Phe106 and Phe345. The analogues adopt an orientation in which ring A
      is located in the orthosteric binding site while the C9 alkoxy substituents
      attached to ring D project into the secondary binding pocket of the D3 receptor.

PMID- 27688183
TI  - Identification of novel microsomal prostaglandin E2 synthase-1 (mPGES-1) lead
      inhibitors from Fragment Virtual Screening.
AB  - Identification of new microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors
      is currently sought for the treatment of cancer and inflammation. Here we show
      the results of a Fragment Virtual Screening campaign using the X-ray crystal
      structure of human mPGES-1 (PDB code: 4AL0). Among the fragments selected and
      biologically tested, 6 (9H-indeno [1,2-b] [1,2,5]oxadiazolo [3,4-e]pyrazin-9-one)
      showed the most promising mPGES-1 inhibitory activity (~30% inhibition at 10
      MUM). A minimal structure-based optimization of 6 led to compounds 15, 20 and 21,
      with a promising enhancement of the inhibitory activity (IC50 = 4.6 +/- 0.2 MUM
      for 15; IC50 = 2.4 +/- 1.0 MUM for 20; IC50 = 2.4 +/- 0.8 MUM for 21). The
      unprecedented chemical core and the possibility of synthesizing novel derivatives
      reveal a new and attractive field of action for the development of mPGES-1
      inhibitors with potential anti-inflammatory and anticancer properties.

PMID- 27688184
TI  - New azepino[4,3-b]indole derivatives as nanomolar selective inhibitors of human
      butyrylcholinesterase showing protective effects against NMDA-induced
      neurotoxicity.
AB  - Several 6-substituted 3,4,5,6-tetrahydroazepino[4,3-b]indol-1(2H)-one (THAI)
      derivatives were synthesized and evaluated for their activity as cholinesterase
      (ChE) inhibitors. The most potent inhibitors were identified among 6-(2
      phenylethyl)-THAI derivatives, and in particular compounds 12b and 12d proved to
      be very active against human BChE (IC50 = 13 and 1.8 nM, respectively), with 1000
      fold selectivity over AChE. Structure-activity relationships highlighted critical
      features (e.g., ring fusion [4,3-b], integrity of the lactam CONH function) and
      favorable physicochemical properties of the 6-(2-phenylethyl) group (i.e.,
      optimal position, size and lipophilicity of phenyl substituents). The effects of
      a number of compounds against NMDA-induced SH-SY5Y neuronal cell injury were also
      evaluated. Treatment with 12b increased cell viability in SH-SY5Y cells
      pretreated with 250 MUM NMDA, with significant effects (P < 0.05) at
      concentrations between 0.5 and 5 MUM. These findings suggest that THAI can be
      used as a scaffold for developing new drug leads for the treatment of Alzheimer
      type neurodegeneration syndrome.

PMID- 27688185
TI  - K-Ras and its inhibitors towards personalized cancer treatment: Pharmacological
      and structural perspectives.
AB  - The discovery of genetic, genomic and clinical biomarkers have revolutionized the
      treatment option in the form of personalized medicine which allows to accurately
      predict a person's susceptibility/progression of disease, the patient's response
      to therapy, and maximize the therapeutic outcome in terms of low/no toxicity for
      a particular patient. Recently, the U.S. Food and Drug Administration has
      realized the contribution of pharmacogenomics in better healthcare and advocated
      the consideration of pharmacogenomic principles in making safer and more
      effective drug. Many anticancer drugs show reduced or no response in cancer
      patients with tumor specific gene mutations such as B-Raf and K-Ras. The high
      incidence of K-Ras mutation has been reported in pancreatic, colon, and lung
      carcinomas. The identification of K-Ras as a clinical biomarker and potential
      therapeutic target has attracted the scientific community to develop effective
      and precise anticancer drug. Inhibitors which block farnesylation of Ras have
      been developed or under clinical trial studies. Tipifarnib, approved by USFDA for
      the treatment of elderly acute leukemia is a Ras pathway inhibitor. Some
      peptidomimetics and bi-substrate inhibitors like FTI 276, FTI 277, B956, B1086,
      L731, L735, L739, L750, BMS-214662, L778123, and L778123 are under clinical
      trials. Recently mutant K-Ras has been considered as potential biomarker and
      target for precise cancer therapy. This review focuses primarily on the
      Ras/Raf/MEK/ERK signaling pathway including K-Ras mutation as therapeutic target,
      inhibitors and their structure activity relationships (SARs) for the design and
      development of anticancer agents.

PMID- 27688186
TI  - Design, synthesis and pharmacological evaluation of 4,5-diarylisoxazols bearing
      amino acid residues within the 3-amido motif as potent heat shock protein 90
      (Hsp90) inhibitors.
AB  - A structure-based medicinal chemistry optimization was conducted on the clinical
      Hsp90 inhibitor diarylisoxazole 3. Several series of new compounds were designed
      and synthesized by incorporating diversified amino acid derivatives with various
      lengths to the 3-amido motif of the isoxazole scaffold. Compound 14j was
      identified to have high Hsp90 binding potency (14 nM) and antiproliferative
      activity against H3122 human lung cancer and BT-474 breast cancer cells.
      Treatment of 14j with H3122 cell led to degradation of client protein ALK,
      reduction of downstream phosphorylation of AKT and ERK, and up-regulation of
      Hsp70. Molecular docking suggested that the terminal valine moiety and the
      ethyleneglycol linker in compound 14j formed additional apolar and polar
      interaction network with a number of amino acid residues.

PMID- 27688187
TI  - Novel 2-arylazoimidazole derivatives as inhibitors of Trypanosoma cruzi
      proliferation: Synthesis and evaluation of their biological activity.
AB  - In this work, the synthesis of a series of 2-arylazoimidazole derivatives 6-20
      has been achieved through the reaction of imidazole with aryldiazonium salts,
      followed by ultrasound-assisted alkylation. This approach has important
      advantages including higher yield, shorter reaction times and milder reaction
      conditions. The structures of the compounds obtained were determined by MS, IR;
      and 1H and 13C NMR. The anti-Trypanosoma cruzi activity of the 15 compounds
      obtained was evaluated. Two compounds with piperidino substituents in the
      carboxamide moiety proved to be effective inhibitors of epimastigote
      proliferation, obtaining inhibition values comparable to those achieved with the
      reference drug Benznidazole. Besides, these compounds displayed low cytotoxicity
      on mammalian cells. In vivo, both compounds protected mice against a challenge
      with a lethal Trypanosoma cruzi strain. These results allow us to propose 2
      arylazoimidazoles as lead compounds for the design of novel drugs to treat
      Chagas' disease.

PMID- 27688188
TI  - Synthesis and antioxidant evaluation of desmethylxanthohumol analogs and their
      dimers.
AB  - Four ring-closed analogs of natural prenylated chalcone desmethylxanthohumol (1)
      and their dimers were synthesized from the commercially available 1-(2,4,6
      trihydroxyphenyl)ethan-1-one in five and six linear steps, respectively. The
      structures of the eight new derivatives were confirmed using1H NMR, 13C NMR and
      HRMS. The antioxidant activity of the new chalcone derivatives were evaluated in
      a PC12 cell model of H2O2-induced oxidative damage. The SAR studies suggested
      that the catechol motif was essential for the antioxidant activity. Moreover, the
      dimers showed better antioxidant activity than their corresponding monomers did.
      Among them, compound 14d was the most potent and increased PC12 cell viability
      from 25% to 85%. Flow cytometric analysis showed that compound 14d, the most
      potent compound, decreased the apoptotic PC12 cell percentage and significantly
      reduced the LDH release and 8-OHdG generation but increased the GSH levels in
      H2O2-treated PC12 cells. Furthermore, compound 14d had a higher FRAP value than
      that of gallic acid. It also reduced the stable ABTS+ free radical with a lower
      EC50 than that of gallic acid.

PMID- 27688189
TI  - Synthesis and in vitro characterization of novel fluorinated derivatives of the
      translocator protein 18 kDa ligand CfO-DPA-714.
AB  - The translocator protein 18 kDa (TSPO) is today a validated target for a number
      of therapeutic applications, but also a well-recognized diagnostic/imaging
      biomarker for the evaluation of inflammatory related-disease state and
      progression, prompting the development of specific and dedicated TSPO ligands
      worldwide. For this purpose, pyrazolo[1,5-a]pyrimidine acetamides constitute a
      unique class of high affinity and selectivity TSPO ligands; it includes DPA-714,
      a fluorine-containing derivative that has also been labelled with the positron
      emitter fluorine-18, and is nowadays widely used as a Positron Emission
      Tomography imaging probe. Recently, to prevent defluorination issues encountered
      in vivo with this tracer, a first series of analogues was reported where the
      oxygen atom bridging the phenyl ring of the core structure and the fluorinated
      moiety was replaced with a more robust linkage. Among this new series, CfO-DPA
      714 was discovered as a highly promising TSPO ligand. Herein, a novel series of
      fluorinated analogues of the latter molecule were synthesized and in vitro
      characterized, where the pharmacomodulation at the amide position of the molecule
      was explored. Thirteen compounds were thus prepared from a common key-ester
      intermediate (synthesized in 7 steps from 4-iodobenzoate - 11% overall yield) and
      a set of commercially available amines and obtained with moderate to good yields
      (23-81%) and high purities (>95%). With one exception, all derivatives displayed
      nanomolar to subnanomolar affinity for the TSPO and also high selectivity versus
      the CBR (Ki (CBR)/Ki (TSPO) > 103). Within this series, three compounds showed
      better Ki values (0.25, 0.26 and 0.30 nM) than that of DPA-714 (0.91 nM) and CfO
      DPA-714 (0.37 nM), and favorable lipophilicity for brain penetration (3.6 <
      logD7.4 < 4.4). Among these three compounds, the N-methyl-N-propyl amide analogue
      (9) exhibited similar metabolic stability when compared to CfO-DPA-714 in mouse,
      rat and human microsomes. Therefore, the latter compound stands out as a
      promising candidate for drug development or for use as a PET probe, once fluorine
      18-labelled, for in vivo neuroinflammation imaging.

PMID- 27688190
TI  - Design, selective alkylation and X-ray crystal structure determination of dihydro
      indolyl-1,2,4-triazole-3-thione and its 3-benzylsulfanyl analogue as potent
      anticancer agents.
AB  - Three sets of substituted indolyl-triazoles were synthesized by the alkylation of
      1,2-dihydro-5-(1H-indol-2-yl)-1,2,4-triazole-3-thione with different alkyl
      halides. The use of pyridine restricted the alkylation to sulfur. Whereas, upon
      using K2CO3, the alkylation exceeded sulfur to one of the remaining triazole
      nitrogens. The assignment of which nitrogen is alkylated besides sulfur is made
      for the first time using X-ray analysis of single crystals and 2D NMR which
      indicated that S-, 2-N-isomers will be preferably formed over the S-, 1-N
      isomers. The antiproliferative activity on HEPG-2 and MCF-7 cancer cell lines was
      tested. The results showed that compound 2a is the most active with an IC50 3.58
      MUg/mL and 4.53 MUg/mL for HEPG-2 and MCF-7 respectively and compound 7 is the
      least active with an IC50 > 100 MUg/mL compared to the standard drug doxorubicin
      (IC50 4.0 MUg/mL). The interaction of the synthesized compounds with tyrosine
      kinases, namely, Akt, PI3, and EGFR was also studied using molecular docking
      simulation to predict their mode of action which will drive future work
      directions.

PMID- 27688191
TI  - Mechanistic and biological characteristics of different sugar conjugated 2-methyl
      malonatoplatinum(II) complexes as new tumor targeting agents.
AB  - Novel cis-2-methylmalonato(trans-R,R-cyclohexane-1,2-diamine)platinum(II)
      glycoconjugates derived from different sugar motifs, namely, glucose (Glu-Me-Pt),
      mannose (Man-Me-Pt) and galactose (Gal-Me-Pt) were designed and synthesized based
      on the third generation clinical drug oxaliplatin for potential glucose
      transporters (GLUTs) mediated tumor targeting. All platinum(II) glycoconjugates
      were characterized by 1H NMR, 13C NMR, IR, HRMS as well as 195Pt-NMR analysis.
      Despite their substantial improvement in water solubility, the conjugates
      exhibited comparable or better in vitro cytotoxicities than oxaliplatin
      determined in six different human cancer cell lines. Glu-Me-Pt has been shown to
      be more effective than cisplatin and oxaliplatin with improved therapeutic index
      in leukemia-bearing DBA/2 mice model. The potential GLUT transportability of the
      complexes was investigated using cell-based fluorescent competition assay and
      GLUT inhibitor mediated cell viability analysis in GLUT over-expressing HT29 cell
      line. Each sugar motif was found to be useful to enable the platinum(II)
      complexes as substrate for GLUT mediated cell uptake. In vitro DNA adduct
      formation analysis has been investigated for the first time for this class of
      compounds to reveal the intrinsic differences in antitumor activity between the
      malonatoplatinum(II) glycoconjugates and oxaliplatin. The intrinsic DNA
      reactivity of the platinum(II)-sugar conjugates was found as Gal-Me-Pt > Glu-Me
      Pt > Man-Me-Pt ~ oxaliplatin by kinetic study on the formation of platinum(II)
      adducts with guanosine-5'-monophosphate (5'-GMP). The results from this study
      demonstrate the usefulness of glucose, mannose and galactose as alternative sugar
      motif on glycoconjugation for GLUT mediated drug design and pharmaceutical R&D,
      and the obtained fundamental results also support the potential of the GLUT
      targeted platinum(II)-sugar conjugates as lead compounds for further pre-clinical
      evaluation.

PMID- 27688192
TI  - Quinolidene-rhodanine conjugates: Facile synthesis and biological evaluation.
AB  - A series of rhodanine incorporated quinoline derivatives were efficiently
      synthesized using reusable DBU acetate as ionic liquid and evaluated for their in
      vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB)
      (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) both in active and dormant
      state. Compounds 3e, 3f, 3g, 3h and 3i exhibited very good antitubercular
      activity. The active compounds were studied for cytotoxicity against HUVEC, THP
      1, macrophages, A549, PANC-1 and HeLa cell lines using modified MTT assay and
      were found to be noncytotoxic. Inactivity of all these compounds against Gram
      positive and Gram negative bacteria indicates their specificity towards the MTB.
      Further, the synthesized compounds have been screened for their in vitro
      antifungal activity. In addition, the molecular docking studies revealed the
      binding modes of these compounds in active site of Zmp1 enzyme, which in turn
      helped to establish a structural basis of inhibition of mycobacteria. The results
      of present study clearly indicate the identification of some novel, selective and
      specific inhibitors against MTB that can be explored further for potential
      antitubercular drug.

PMID- 27688193
TI  - Design, synthesis and docking studies of novel 1,2-dihydro-4-hydroxy-2
      oxoquinoline-3-carboxamide derivatives as a potential anti-proliferative agents.
AB  - A new series of 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide
      hybrids 8a-l have been designed and synthesized using peptide coupling agents
      with substituted N-phenyl piperazines and piperidines with good to excellent
      yields. The synthesized compounds were evaluated for their in vitro anti
      proliferative activity against PANC 1, HeLa and MDA-MB-231. The compounds 8d, 8e,
      8f, 8g, 8h and 8k exhibited considerable anti-proliferative activity with GI50
      values ranging from 0.15 to 1.4 MUM. The structure and anti-proliferative
      activity relationship was further supported by in silico molecular docking study
      of the active compounds against tubulin protein.

PMID- 27688194
TI  - Zika Virus Disease: Should we be Worried?

PMID- 27688196
TI  - Erratum.

PMID- 27688195
TI  - Addiction to RUNX in lymphoma.

PMID- 27688197
TI  - "Ictal catatonia": Rare but not to be missed!

PMID- 27688198
TI  - Response to the letter: "Obsessive compulsive personality disorder in Progressive
      Supranuclear Palsy" by Golimstok.

PMID- 27688199
TI  - Obsessive compulsive personality disorder and Progressive Supranuclear Palsy.

PMID- 27688200
TI  - Cognitive and psychiatric outcome 3 years after globus pallidus pars interna or
      subthalamic nucleus deep brain stimulation for Parkinson's disease.
AB  - BACKGROUND: Effects on non-motor symptoms, mainly cognitive and psychiatric side
      effects, could influence the decision for either globus pallidus pars interna
      (GPi) or subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with
      Parkinson's disease (PD). OBJECTIVE: 1) To compare cognitive and psychiatric
      outcomes 3 years after GPi DBS versus STN DBS, and 2) to report on occurrence of
      suicidal ideation, psychiatric diagnoses, social functioning, and marital
      satisfaction 3 years after DBS. METHODS: Patients were randomized to receive GPi
      DBS (n = 65) or STN DBS (n = 63). Standardized assessments were performed at
      baseline, 1 year, and 3 years. We used linear mixed model analyses to investigate
      between-group differences on the Mattis Dementia Rating Scale (MDRS),
      neuropsychological tests, and psychiatric questionnaires 3 years after DBS.
      RESULTS: Eighty-seven patients (68%) completed at least one neuropsychological
      test after 3 years. No significant between-group differences were found on the
      MDRS (p = 0.61), neuropsychological tests (p-values between 0.17 and 0.87), and
      psychiatric questionnaires (p-values between 0.23 and 0.88) 3 years after DBS.
      The Mini International Neuropsychiatric Interview did not indicate a substantial
      number of psychiatric diagnoses after 3 years. Social functioning and marital
      satisfaction were comparable in both groups. CONCLUSIONS: Three years after GPi
      DBS and STN DBS no pronounced between-group differences on measures of cognitive
      and psychiatric functioning could be demonstrated. Overall, cognitive and
      psychiatric outcome 3 years after DBS do not provide a clear direction for
      clinicians when considering which of these two surgical targets to choose.

PMID- 27688201
TI  - Do tumor necrosis factor inhibitors increase cancer risk in patients with chronic
      immune-mediated inflammatory disorders?
AB  - Inhibition of tumor necrosis factor (TNF) activity has profoundly changed the
      management of several immune-mediated inflammatory diseases with great benefit
      for patients. The application of TNF inhibitors (TNFi), however, also brings a
      new concern, malignancy. We performed a systemic review to collect the studies
      reporting cancer incidences and risks in TNFi users regardless of indications.
      TNFi were most frequently used in treating patients with rheumatoid arthritis
      (RA) and inflammatory bowel diseases (IBD). In RA patients without prior cancer
      history, the incidences of malignancies ranged from the lowest rate 0 per 1000
      person-years in etanercept users regarding lymphoma to the highest rate 35.62 per
      1000 person-years in adalimumab users on non-melanoma skin cancer (NMSC), while
      in those patients with prior cancer history, the recurrent incidences of
      malignancies ranged from the lowest rate 5.05 per 1000 person-years regarding
      melanoma to the highest rate 63.20 per 1000 person-years on basal cell carcinoma
      (BCC) in TNFi users. In IBD patients, incidences ranged from 0 per 1000 person
      years in TNFi users on lymphoma to 34.0 per 1000 person-years in infliximab users
      on overall cancer. However, these incidence rates of overall cancer, lymphoma and
      melanoma were not higher in comparison with those patients who were not treated
      with TNFi. Compared to general population, incidences of lymphoma were elevated
      in RA patients and rates of NMSC were higher in patients with psoriasis, RA and
      IBD. In conclusion, cancer incidences vary across different studies, indications,
      cancer types and studies with different individual TNFi. Treatment with TNFi is
      not associated with increased malignant risks of overall cancer, lymphoma or
      melanoma. Results of NMSC risk were inconsistent among studies. A latest
      prospective registry study demonstrated a small increased risk of squamous cell
      cancer in RA patients treated with TNFi (one additional case for every 1600years
      of treatment experience). Further prospective studies are needed to verify
      whether TNFi users have higher NMSC risk than non-TNFi users.

PMID- 27688202
TI  - Cerebral neural correlates of differential melanopic photic stimulation in
      humans.
AB  - Photic stimulation of rods, cones and intrinsically photosensitive melanopsin
      containing retinal ganglion cells (ipRGCs) mediates non-visual light responses,
      including entrainment of circadian rhythms and pupillary light reflex. Unlike
      visual responses to photic stimulation, the cerebral correlates of non-visual
      light responses in humans remains elusive. In this study, we used functional
      magnetic resonance imaging (fMRI) in 14 healthy young participants, to localize
      cerebral regions which are differentially activated by metameric light that gave
      rise to different levels of melanopic excitation. Mean blood oxygen-level
      dependent (BOLD) responses disclosed bilateral activation of the frontal eye
      fields during exposure to light geared towards melanopsin. Furthermore,
      multivariate pattern analyses showed distinct bilateral pattern activity in the
      inferior temporal gyri and the caudate nuclei. Taken together, our findings
      suggest that melanopsin-based photoreception activates a cerebral network
      including frontal regions, classically involved in attention and ocular motor
      responses.

PMID- 27688203
TI  - Individualized parcellation of the subthalamic nucleus in patients with
      Parkinson's disease with 7T MRI.
AB  - Deep brain stimulation of the subthalamic nucleus (STN) is a widely performed
      surgical treatment for patients with Parkinson's disease. The goal of the surgery
      is to place an electrode centered in the motor region of the STN while lowering
      the effects of electrical stimulation on the non-motor regions. However,
      distinguishing the motor region from the neighboring associative and limbic areas
      in individual patients using imaging modalities was until recently difficult to
      obtain in vivo. Here, using ultra-high field MR imaging, we have performed a
      dissection of the subdivisions of the STN of individual Parkinson's disease
      patients. We have acquired 7T diffusion-weighted images of seventeen patients
      with Parkinson's disease scheduled for deep brain stimulation surgery. Using a
      structural connectivity-based parcellation protocol, the STN's connections to the
      motor, limbic, and associative cortical areas were used to map the individual
      subdivisions of the nucleus. A reproducible patient-specific parcellation of the
      STN into a posterolateral motor and gradually overlapping central associative
      area was found in all STNs, taking up on average 55.3% and 55.6% of the total
      nucleus volume. The limbic area was found in the anteromedial part of the
      nucleus. Our results suggest that 7T MR imaging may facilitate individualized and
      highly specific planning of deep brain stimulation surgery of the STN.

PMID- 27688204
TI  - Reading in dyslexia across literacy development: A longitudinal study of
      effective connectivity.
AB  - Dyslexia is a literacy disorder affecting the efficient acquisition of reading
      and writing skills. The disorder is neurobiological in origin. Due to its
      developmental nature, longitudinal studies of dyslexia are of essence. They are,
      however, relatively scarce. The present study took a longitudinal approach to
      cortical connectivity of brain imaging data in reading tasks in children with
      dyslexia and children with typical reading development. The participants were
      followed with repeated measurements through Pre-literacy (6 years old), Emergent
      Literacy (8 years old) and Literacy (12 years old) stages, using Dynamic Causal
      Modelling (DCM) when analysing functional magnetic resonance imaging (fMRI) data.
      Even though there are a few longitudinal studies on effective connectivity in
      typical reading, to our knowledge, no studies have previously investigated these
      issues in relation to dyslexia. We set up a model of a brain reading network
      involving five cortical regions (inferior frontal gyrus, precentral gyrus,
      superior temporal gyrus, inferior parietal lobule, and occipito-temporal cortex).
      Using DCM, connectivity measures were calculated for each connection in the
      model. These measures were further analysed using factorial ANOVA. The results
      showed that the difference between groups centred on connections going to and
      from the inferior frontal gyrus (two connections) and the occipito-temporal
      cortex (three connections). For all five connections, the typical group showed
      stable or decreasing connectivity measures. The dyslexia group, on the other
      hand, showed a marked up-regulation (occipito-temporal connections) or down
      regulation (inferior frontal gyrus connections) from 6 years to 8 years, followed
      by normalization from 8 years to 12 years. We interpret this as a delay in the
      dyslexia group in developing into the Pre-literacy and Emergent literacy stages.
      This delay could possibly be detrimental to literacy development. By age 12,
      there was no statistically significant difference in connectivity between the
      groups, but differences in literacy skills were still present, and were in fact
      larger than when measured at younger ages.

PMID- 27688205
TI  - Endoscopic submucosal dissection for Barrett's early neoplasia: a multicenter
      study in the United States.
AB  - BACKGROUND AND AIMS: The role of endoscopic submucosal dissection (ESD) in
      Barrett's early neoplasia is not well defined, with most studies originating from
      Asia and Europe. We aimed to assess the efficacy, safety, and results of ESD in
      Barrett's esophagus (BE) with high-grade dysplasia (HGD) and early adenocarcinoma
      (EAC) across centers in the United States. METHODS: Multicenter retrospective
      analysis on 46 patients with BE who underwent ESD for BE-HGD or EAC, or both,
      between January 2010 and April 2015. The primary endpoint was the rate of en bloc
      resection. Secondary aims included rate of R0 (complete) and curative resection,
      a comparison of pre- and post-ESD histology, procedure-related adverse events,
      and rate of remission at follow-up. RESULTS: Median age was 69 years (range, 42
      82 years). The median resected specimen size was 45 mm (range, 13-125 mm). En
      bloc and curative resection rates were 96% (44/46) and 70% (32/46), respectively.
      Most lesions (11/20; 55%) diagnosed as BE-HGD on biopsy were upstaged to
      intramucosal or invasive EAC on post-ESD histopathology. There were 4 early (<48
      hours) adverse events (3 bleeding and 1 perforation), and all were treated
      endoscopically. Seven patients (15%) developed esophageal strictures that were
      managed endoscopically. Complete remission of BE neoplasia was found in 100%
      (32/32) of patients with curative resection at median follow-up of 11 months
      (range, 2-25 months). CONCLUSIONS: This is the largest multicenter series of ESD
      for early neoplastic BE from the United States. ESD appears to be safe and
      effective, with high en bloc and curative resection rates in the treatment of
      early BE neoplasia.

PMID- 27688206
TI  - Arbuscular Mycorrhizal Symbiosis Requires a Phosphate Transceptor in the
      Gigaspora margarita Fungal Symbiont.
AB  - The majority of terrestrial vascular plants are capable of forming mutualistic
      associations with obligate biotrophic arbuscular mycorrhizal (AM) fungi from the
      phylum Glomeromycota. This mutualistic symbiosis provides carbohydrates to the
      fungus, and reciprocally improves plant phosphate uptake. AM fungal transporters
      can acquire phosphate from the soil through the hyphal networks. Nevertheless,
      the precise functions of AM fungal phosphate transporters, and whether they act
      as sensors or as nutrient transporters, in fungal signal transduction remain
      unclear. Here, we report a high-affinity phosphate transporter GigmPT from
      Gigaspora margarita that is required for AM symbiosis. Host-induced gene
      silencing of GigmPT hampers the development of G. margarita during AM symbiosis.
      Most importantly, GigmPT functions as a phosphate transceptor in G. margarita
      regarding the activation of the phosphate signaling pathway as well as the
      protein kinase A signaling cascade. Using the substituted-cysteine accessibility
      method, we identified residues A146 (in transmembrane domain [TMD] IV) and Val357
      (in TMD VIII) of GigmPT, both of which are critical for phosphate signaling and
      transport in yeast during growth induction. Collectively, our results provide
      significant insights into the molecular functions of a phosphate transceptor from
      the AM fungus G. margarita.

PMID- 27688208
TI  - Resection of highly language-eloquent brain lesions based purely on rTMS language
      mapping without awake surgery.
AB  - BACKGROUND: The resection of left-sided perisylvian brain lesions harbours the
      risk of postoperative language impairment. Therefore the individual patient's
      language distribution is investigated by intraoperative direct cortical
      stimulation (DCS) during awake surgery. Yet, not all patients qualify for awake
      surgery. Non-invasive language mapping by repetitive navigated transcranial
      magnetic stimulation (rTMS) has frequently shown a high correlation in comparison
      with the results of DCS language mapping in terms of language-negative brain
      regions. The present study analyses the extent of resection (EOR) and functional
      outcome of patients who underwent left-sided perisylvian resection of brain
      lesions based purely on rTMS language mapping. METHODS: Four patients with left
      sided perisylvian brain lesions (two gliomas WHO III, one glioblastoma, one
      cavernous angioma) underwent rTMS language mapping prior to surgery. Data from
      rTMS language mapping and rTMS-based diffusion tensor imaging fibre tracking (DTI
      FT) were transferred to the intraoperative neuronavigation system.
      Preoperatively, 5 days after surgery (POD5), and 3 months after surgery (POM3)
      clinical follow-up examinations were performed. RESULTS: No patient suffered from
      a new surgery-related aphasia at POM3. Three patients underwent complete
      resection immediately, while one patient required a second rTMS-based resection
      some days later to achieve the final, complete resection. CONCLUSIONS: The
      present study shows for the first time the feasibility of successfully resecting
      language-eloquent brain lesions based purely on the results of negative language
      maps provided by rTMS language mapping and rTMS-based DTI-FT. In very select
      cases, this technique can provide a rescue strategy with an optimal functional
      outcome and EOR when awake surgery is not feasible.

PMID- 27688209
TI  - D-Xylose fermentation, xylitol production and xylanase activities by seven new
      species of Sugiyamaella.
AB  - Sixteen yeast isolates identified as belonging to the genus Sugiyamaella were
      studied in relation to D-xylose fermentation, xylitol production, and xylanase
      activities. The yeasts were recovered from rotting wood and sugarcane bagasse
      samples in different Brazilian regions. Sequence analyses of the internal
      transcribed spacer (ITS) region and the D1/D2 domains of large subunit rRNA gene
      showed that these isolates belong to seven new species. The species are described
      here as Sugiyamaella ayubii f.a., sp. nov. (UFMG-CM-Y607T = CBS 14108T),
      Sugiyamaella bahiana f.a., sp. nov. (UFMG-CM-Y304T = CBS 13474T), Sugiyamaella
      bonitensis f.a., sp. nov. (UFMG-CM-Y608T = CBS 14270T), Sugiyamaella carassensis
      f.a., sp. nov. (UFMG-CM-Y606T = CBS 14107T), Sugiyamaella ligni f.a., sp. nov.
      (UFMG-CM-Y295T = CBS 13482T), Sugiyamaella valenteae f.a., sp. nov. (UFMG-CM
      Y609T = CBS 14109T) and Sugiyamaella xylolytica f.a., sp. nov. (UFMG-CM-Y348T =
      CBS 13493T). Strains of the described species S. boreocaroliniensis, S.
      lignohabitans, S. novakii and S. xylanicola, isolated from rotting wood of
      Brazilian ecosystems, were also compared for traits relevant to xylose
      metabolism. S. valenteae sp. nov., S. xylolytica sp. nov., S. bahiana sp. nov.,
      S. bonitensis sp. nov., S. boreocarolinensis, S. lignohabitans and S. xylanicola
      were able to ferment D-xylose to ethanol. Xylitol production was observed for all
      Sugiyamaella species studied, except for S. ayubii sp. nov. All species studied
      showed xylanolytic activity, with S. xylanicola, S. lignohabitans and S.
      valenteae sp. nov. having the highest values. Our results suggest these
      Sugiyamaella species have good potential for biotechnological applications.

PMID- 27688210
TI  - Microbacterium rhizosphaerae sp. nov., isolated from a Ginseng field, South
      Korea.
AB  - A novel Gram-stain positive, aerobic, short rod-shaped, non-motile bacterium,
      designated strain CHO1T, was isolated from rhizosphere soil from a ginseng
      agriculture field. Strain CHO1T was observed to form yellow colonies on R2A agar
      medium. The cell wall peptidoglycan was found to contain alanine, glycine,
      glutamic acid, D-ornithine and serine. The cell wall sugars were identified as
      galactose, mannose, rhamnose and ribose. Strain CHO1T was found to contain MK-11,
      MK-12, MK-13 as the predominant menaquinones and anteiso-C15:0, iso-C16:0, and
      anteiso-C17:0 as the major fatty acids. Diphosphatidylglycerol,
      phosphatidylglycerol, phosphoglycolipid, an unidentified phospholipid and three
      unidentified glycolipids were found to be present in strain CHO1T. Based on 16S
      rRNA gene sequence analysis, strain CHO1T was found to be closely related to
      Microbacterium mangrovi DSM 28240T (97.81 % similarity), Microbacterium
      immunditiarum JCM 14034T (97.45 %), Microbacterium oryzae JCM 16837T (97.33 %)
      and Microbacterium ulmi KCTC 19363T (97.10 %) and to other species of the genus
      Microbacterium. The DNA G+C content of CHO1T was determined to be 70.1 mol %. The
      DNA-DNA hybridization values of CHO1T with M. mangrovi DSM 28240T, M.
      immunditiarum JCM 14034T, M. oryzae JCM 16837T and M. ulmi KCTC 19363T were 46.7
      +/- 2, 32.4 +/- 2, 32.0 +/- 2 and 29.2 +/- 2 %, respectively. On the basis of
      genotypic, phenotypic and phylogenetic properties, it is concluded that strain
      CHO1T represents a novel species within the genus Microbacterium, for which the
      name Microbacterium rhizosphaerae sp. nov. is proposed. The type strain of M.
      rhizosphaerae is CHO1T (= KEMB 7306-513T = JCM 31396T).

PMID- 27688211
TI  - Reclassification of Halomonas caseinilytica Wu et al. 2008 as a later synonym of
      Halomonas sinaiensis-Comments on the proposal by Hwang et al., Antonie van
      Leeuwenhoek 109:1345-1352, 2016.
AB  - Hwang et al. (Antonie van Leeuwenhoek 109:1345-1352, 2016) proposed the
      reclassification of Halomonas caseinilytica (Wu et al. 2008) as a later synonym
      of Halomonas sinaiensis, based on the publication of the latter name in 2007 by
      Romano et al. However, the name H. sinaiensis was validly published only in 2011.
      Therefore the proposal by Hwang et al. is not appropriate; instead, the name H.
      sinaiensis can be proposed as a later synonym of H. casinilytica.

PMID- 27688207
TI  - Applications of Extracellular RNAs in Oncology.
AB  - Extracellular RNAs consist of coding and non-coding transcripts released from all
      cell types, which are involved in multiple cellular processes, predominantly
      through regulation of gene expression. Recent advances have helped us better
      understand the functions of these molecules, particularly microRNAs (miRNAs).
      Numerous pre-clinical and human studies have demonstrated that miRNAs are
      dysregulated in cancer and contribute to tumorigenesis and metastasis. miRNA
      profiling has extensively been evaluated as a non-invasive method for cancer
      diagnosis, prognostication, and assessment of response to cancer therapies.
      Broader applications for miRNAs in these settings are currently under active
      development. Investigators have also moved miRNAs into the realm of cancer
      therapy. miRNA antagonists targeting miRNAs that silence tumor suppressor genes
      have shown promising pre-clinical activity. Alternatively, miRNA mimics that
      silence oncogenes are also under active investigation. These miRNA-based cancer
      therapies are in early development, but represent novel strategies for clinical
      management of human cancer.

PMID- 27688213
TI  - Mucosal Perforation During Laparoscopic Heller Myotomy Has No Influence on Final
      Treatment Outcome.
AB  - BACKGROUND: The aims of the study were (a) to examine the final outcome in
      patients experiencing accidental mucosal perforation during laparoscopic Heller
      myotomy with Dor fundoplication (LHD) and (b) to evaluate whether perforation
      episodes might influence the way in which surgeons subsequently approached the
      LHD procedure. METHODS: We studied all consecutive patients that underwent LHD
      between 1992 and 2015. Patients were divided into two main groups: those who
      experienced an intraoperative mucosal perforation (group P) and those whose LHD
      was uneventful (group NP). Two additional groups were compared: group A, which
      consisted of patients operated by a given surgeon immediately before a
      perforation episode occurred, and group B, which included those operated
      immediately afterwards. RESULTS: Eight hundred seventy-five patients underwent
      LHD; a mucosal perforation was detected in 25 patients (2.9 %), which was found
      unrelated to patients' symptom's score and age, radiological stage, manometric
      pattern, or the surgeon's experience. The median postoperative symptom score was
      similar for the two groups as the failure rate: 92 failures in group NP (10.8 %)
      and 4 in group P (16 %) (p = 0.34); moreover, symptoms recurred in 2 patients of
      group A (10 %) and 3 patients of group B (15 %) (p = 0.9). CONCLUSIONS:
      Accidental perforation during LHD is infrequent and impossible to predict on the
      grounds of preoperative therapy or the surgeon's personal experience. Despite a
      longer surgical procedure and hospital stay, the outcome of LHD is much the same
      as for patients undergoing uneventful myotomy. A recent mucosal perforation does
      not influence the surgeon's subsequent performance.

PMID- 27688214
TI  - The Clinical Utility of Over-the-Scope Clip for the Treatment of Gastrointestinal
      Defects.
AB  - BACKGROUND: The over-the-scope clip (OTSC) is a novel endoscopic tool that
      enables non-surgical management of gastrointestinal (GI) defects. The aim of this
      study was to report our experience with OTSC for patients with GI defects.
      METHODS: A prospectively maintained IRB-approved institutional database was
      queried for all patients treated with OTSC from 2012 to 2015. Primary outcome was
      the clinical success of the OTSC for the individual indication. Secondary outcome
      was the number of additional procedures needed following OTSC. RESULTS: Fifty-one
      patients were treated with OTSC: upper GI (UGI) 30 and lower GI (LGI) 21. GI leak
      (n = 24; UGI = 12, LGI = 12) and fistulae (n = 17; UGI = 8, LGI = 9) were the
      most common indications. Overall success rate for the treatment of leaks was 59 %
      [UGI 66 % vs. LGI 33 % (p = 0.1)]. A lower success rate (35 %) was noted for
      fistulae [UGI 62 % vs. LGI 0 % (p = 0.001)]. Success rates for UGI perforation,
      bleeding, and stent anchoring indications were 75, 75, and 50 %, respectively.
      Additional endoscopic or surgical interventions following OTSC were indicated in
      68.6 % of the patients. CONCLUSIONS: OTSC appears to have additional value in
      treating UGI defects. However, lower success rates for LGI defects were noted,
      specifically for fistulae. Most patients require an additional endoscopic or
      surgical procedure after one OTSC application.

PMID- 27688212
TI  - Patient Adherence and Experience with Extended Use of Prophylactic Low-Molecular
      Weight Heparin Following Pancreas and Liver Resection.
AB  - BACKGROUND: Guidelines recommend 28 days venous thromboembolism (VTE) prophylaxis
      with low-molecular-weight heparin (LMWH) following major abdominal surgery for
      cancer. Overall adherence with these recommendations is poor, but little is known
      about feasibility and tolerability from a patient perspective. METHODS: An
      institution-wide policy for routine administration of 28 days of post-operative
      LMWH following major hepatic or pancreatic resection for cancer was implemented
      in April 2013. Patients having surgery from July 2013 to June 2015 were
      approached to participate in an interview examining adherence and experience with
      extended duration LMWH. RESULTS: There were 100 patients included, with 81.4 %
      reporting perfect adherence with the regimen. The most frequent reasons for non
      adherence were that a healthcare provider stopped the regimen or because of poor
      experience with injections. Most patients were able to correctly recall the
      reason for being prescribed LMWH (82.6 %), and 78.4 % of patients performed all
      injections themselves. Over half the patients (55.7 %) did not find the
      injections bothersome. CONCLUSION: Patients reported high adherence and a
      manageable experience with post-operative extended-duration LMWH in an ambulatory
      setting following liver or pancreas resection. These findings suggest that
      patient adherence is not a major contributor to poor compliance with VTE
      prophylaxis guidelines.

PMID- 27688218
TI  - Nonlinear statistical data assimilation for HVC[Formula: see text] neurons in the
      avian song system.
AB  - With the goal of building a model of the HVC nucleus in the avian song system, we
      discuss in detail a model of HVC[Formula: see text] projection neurons comprised
      of a somatic compartment with fast Na[Formula: see text] and K[Formula: see text]
      currents and a dendritic compartment with slower Ca[Formula: see text] dynamics.
      We show this model qualitatively exhibits many observed electrophysiological
      behaviors. We then show in numerical procedures how one can design and analyze
      feasible laboratory experiments that allow the estimation of all of the many
      parameters and unmeasured dynamical variables, given observations of the somatic
      voltage [Formula: see text] alone. A key to this procedure is to initially
      estimate the slow dynamics associated with Ca, blocking the fast Na and K
      variations, and then with the Ca parameters fixed estimate the fast Na and K
      dynamics. This separation of time scales provides a numerically robust method for
      completing the full neuron model, and the efficacy of the method is tested by
      prediction when observations are complete. The simulation provides a framework
      for the slice preparation experiments and illustrates the use of data
      assimilation methods for the design of those experiments.

PMID- 27688220
TI  - Effects of Kinesio taping compared to arterio-venous Impulse SystemTM on limb
      swelling and skin temperature after total knee arthroplasty.
AB  - PURPOSE: It is an established fact that post-operative (p.o.) soft-tissue
      swelling and lymphoedema after total knee arthroplasty (TKA) have a major
      influence on the p.o. early functional outcome. Kinesio taping has a proven
      clinical effect in increasing lymph drainage. Despite the decades of experience
      gained and the assumed positive effects, hardly any investigations have been
      conducted to date on the influence of Kinesio taping on the p.o. healing process
      after TKA. The objective of the present study was to test the hypothesis that
      Kinesio taping used as a lymph application leads to a reduction of p.o. soft
      tissue swelling. As a secondary objective, it was to be tested whether there is
      an effect on skin temperature as a surrogate parameter for dermal micro
      circulation. METHODS: In this prospective study with a historical control (A-V
      Impulse SystemTM group), 42 subjects were included and treated with Kinesio
      taping after implantation of a TKA. The patients of the study group were treated
      immediately p.o. with Kinesio(r) Tex GoldTM fan cut tape as a lymph application
      with a common base. A thermographic temperature determination of the knee joint
      operated on was performed on each patient in the supine position every day from
      the first to the seventh p.o. day. The leg circumference was documented daily at
      eight specified measuring points on both lower limbs. As a statistical analytical
      approach, the so-called principal component analysis was used. An analysis of
      variance was performed. The significance level was set at p < 0.001. RESULTS: The
      course of soft-tissue swelling of the study group did not differ from that of the
      control group at any point in time. For the temperature course of the medial
      wound aspect, no difference was seen between the Kinesio taping study group and
      the A-V Impulse SystemTM group. In contrast, the temperature course of the
      lateral wound aspect showed a reproducibly higher temperature in the Kinesio tape
      group than in the control group (0.6  degrees C (0.5-0.8), p < 0.001).
      CONCLUSION: The hypothesis of the study that Kinesio taping as a lymph
      application induces a reduction of soft-tissue swelling after TKA must be
      rejected on the basis of the present data. Solely the temperature of the lateral
      wound aspect was higher in the Kinesio taping group than in the control group, so
      that an increased blood circulation can be assumed here. Considering that the
      actively working A-V Impulse SystemTM used in the control group also increases
      local blood circulation, the effect of the passive Kinesio tape is surprising.
      However, this was not reflected in a quicker wound healing, as the day of last
      wound secretion was the same in both groups. Kinesio taping as a lymph
      application represents an equivalent alternative to the A-V Impulse SystemTM for
      therapy after total knee arthroplasty with regard to soft-tissue swelling and
      wound healing.

PMID- 27688221
TI  - Examining Smoking Cessation in a Community-Based Versus Clinic-Based Intervention
      Using Community-Based Participatory Research.
AB  - Tobacco use remains a major public health problem in the U.S. disproportionately
      affecting underserved communities. The Communities Engaged and Advocating for a
      Smoke-free Environment (CEASE) initiative is an intervention to address the
      problem using a community-based participatory research (CBPR) approach. This
      study compares quit rates in a peer-led community-based intervention with those
      achieved in a clinical setting. The intervention consisted of three Phases. Phase
      I (n = 404) was a clinic-based trial comparing two types of counseling. Phase II
      (n = 398) and Phase III (n = 163) interventions were conducted in community
      venues by trained Peer Motivators. Quit rates at 12-week follow-up increased from
      9.4 % in Phase I (clinic-based) to an average of 23.7 % in Phases II and III
      combined (community-based). The main predictor of smoking cessation was delivery
      of services in community settings (OR 2.6, 95 % CI 1.7-4.2) while controlling for
      possible confounders. A community-based approach can significantly guide and
      improve effectiveness and acceptability of smoking cessation services designed
      for low-income urban populations. In addition, CBPR can result in better
      recruitment and retention of the participants.

PMID- 27688222
TI  - Antibiotics: The good, the bad, and the ugly.

PMID- 27688219
TI  - Strengthening Health Systems While Responding to a Health Crisis: Lessons Learned
      by a Nongovernmental Organization During the Ebola Virus Disease Epidemic in
      Sierra Leone.
AB  - An epidemic of Ebola virus disease (EVD) beginning in 2013 has claimed an
      estimated 11 310 lives in West Africa. As the EVD epidemic subsides, it is
      important for all who participated in the emergency Ebola response to reflect on
      strengths and weaknesses of the response. Such reflections should take into
      account perspectives not usually included in peer-reviewed publications and after
      action reports, including those from the public sector, nongovernmental
      organizations (NGOs), survivors of Ebola, and Ebola-affected households and
      communities. In this article, we first describe how the international NGO
      Partners In Health (PIH) partnered with the Government of Sierra Leone and
      Wellbody Alliance (a local NGO) to respond to the EVD epidemic in 4 of the
      country's most Ebola-affected districts. We then describe how, in the aftermath
      of the epidemic, PIH is partnering with the public sector to strengthen the
      health system and resume delivery of regular health services. PIH's experience in
      Sierra Leone is one of multiple partnerships with different stakeholders. It is
      also one of rapid deployment of expatriate clinicians and logistics personnel in
      health facilities largely deprived of health professionals, medical supplies, and
      physical infrastructure required to deliver health services effectively and
      safely. Lessons learned by PIH and its partners in Sierra Leone can contribute to
      the ongoing discussion within the international community on how to ensure
      emergency preparedness and build resilient health systems in settings without
      either.

PMID- 27688223
TI  - NASAL MRSA Carriage Rates.

PMID- 27688224
TI  - TMD Diagnostic Criteria.

PMID- 27688225
TI  - Authors' response.

PMID- 27688226
TI  - Authors' response.

PMID- 27688227
TI  - Bisphosphonate-Related Osteonecrosis of the Jaw.

PMID- 27688228
TI  - More on BRONJ.

PMID- 27688230
TI  - Correction.

PMID- 27688229
TI  - Authors' response.

PMID- 27688231
TI  - A higher incidence of dry socket may be related to the use of oral contraceptives
      after impacted mandibular third-molar extraction.

PMID- 27688232
TI  - Improvement ideas from the experts-patients and staff members.

PMID- 27688233
TI  - Caught between a rock and a hard place.

PMID- 27688234
TI  - Recent progress and performance evaluation for polyaniline/graphene
      nanocomposites as supercapacitor electrodes.
AB  - Polyaniline (PANi)/graphene nanocomposites have attracted tremendous interest
      because of their great potential in electrochemical energy storage applications,
      especially supercapacitors. We herein focus on the composite synthesis, device
      fabrication and particularly various techniques for the improvement of
      electrochemical performance. It is imperative to take close control of the
      interface in these nanostructured composites, which thus would lead to the
      desired synergistic effects and cyclic stability with the efficient diffusion of
      electrolyte ions and electrons. Challenges and perspectives are discussed for the
      development of highly efficient PANi/graphene electrodes for supercapacitors.

PMID- 27688235
TI  - Location of In-Hospital Cardiac Arrest in the United States-Variability in Event
      Rate and Outcomes.
AB  - BACKGROUND: In-hospital cardiac arrest (IHCA) is a major public health problem
      with significant mortality. A better understanding of where IHCA occurs in
      hospitals (intensive care unit [ICU] versus monitored ward [telemetry] versus
      unmonitored ward) could inform strategies for reducing preventable deaths.
      METHODS AND RESULTS: This is a retrospective study of adult IHCA events in the
      Get with the Guidelines-Resuscitation database from January 2003 to September
      2010. Unadjusted analyses were used to characterize patient, arrest, and hospital
      level characteristics by hospital location of arrest (ICU versus inpatient ward).
      IHCA event rates and outcomes were plotted over time by arrest location. Among 85
      201 IHCA events at 445 hospitals, 59% (50 514) occurred in the ICU compared to
      41% (34 687) on the inpatient wards. Compared to ward patients, ICU patients were
      younger (64+/-16 years versus 69+/-14; P<0.001) and more likely to have a
      presenting rhythm of ventricular tachycardia/ventricular fibrillation (21% versus
      17%; P<0.001). In the ICU, mean event rate/1000 bed-days was 0.337 (+/-0.215)
      compared with 0.109 (+/-0.079) for telemetry wards and 0.134 (+/-0.098) for
      unmonitored wards. Of patients with an arrest in the ICU, the adjusted mean
      survival to discharge was 0.140 (0.037) compared with the unmonitored wards 0.106
      (0.037) and telemetry wards 0.193 (0.074). More IHCA events occurred in the ICU
      compared to the inpatient wards and there was a slight increase in events/1000
      patient bed-days in both locations. CONCLUSIONS: Survival rates vary based on
      location of IHCA. Optimizing patient assignment to unmonitored wards versus
      telemetry wards may contribute to improved survival after IHCA.

PMID- 27688237
TI  - Common Statistical Pitfalls in Basic Science Research.

PMID- 27688236
TI  - Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery
      (CRIPES): A Prospective, Randomized, Sham-Controlled Phase II Clinical Trial.
AB  - BACKGROUND: Remote ischemic preconditioning (RIPC) has been shown to reduce
      infarct size in animal models. We hypothesized that RIPC before an elective
      vascular operation would reduce the incidence and amount of a postoperative rise
      of the cardiac troponin level. METHODS AND RESULTS: Cardiac Remote Ischemic
      Preconditioning Prior to Elective Vascular Surgery (CRIPES) was a prospective,
      randomized, sham-controlled phase 2 trial using RIPC before elective vascular
      procedures. The RIPC protocol consisted of 3 cycles of 5-minute forearm ischemia
      followed by 5 minutes of reperfusion. The primary endpoint was the proportion of
      subjects with a detectable increase in cardiac troponin I (cTnI) and the
      distribution of such increases. From June 2011 to September 2015, 201 male
      patients (69+/-7, years) were randomized to either RIPC (n=100) or a sham
      procedure (n=101). Indications for vascular surgery included an expanding
      abdominal aortic aneurysm (n=115), occlusive peripheral arterial disease of the
      lower extremities (n=37), or internal carotid artery stenosis (n=49). Of the 201
      patients, 47 (23.5%) had an increase in cTnI above the upper reference limit
      within 72 hours of the vascular operation, with no statistically significant
      difference between those patients assigned to RIPC (n=22; 22.2%) versus sham
      procedure (n=25; 24.7%; P=0.67). Among the cohort with increased cTnI, the median
      peak values (interquartile range) in the RIPC and control group were 0.048 (0.004
      0.174) and 0.017 (0.003-0.105), respectively (P=0.54). CONCLUSIONS: In this
      randomized, controlled trial of men with increased perioperative cardiac risks,
      elevation in cardiac troponins was common following vascular surgery, but was not
      reduced by a strategy of RIPC. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT01558596.

PMID- 27688238
TI  - Sex Differences and Survival in Adults With Bicuspid Aortic Valves: Verification
      in 3 Contemporary Echocardiographic Cohorts.
AB  - BACKGROUND: Sex-related differences in morbidity and survival in bicuspid aortic
      valve (BAV) adults are fundamentally unknown. Contemporary studies portend
      excellent survival for BAV patients identified at early echocardiographic
      clinical stages. Whether BAV adults incur a survival disadvantage throughout
      subsequent echocardiographic-clinical stages remains undetermined. METHODS AND
      RESULTS: Analysis was done of 3 different cohorts of consecutive patients with
      echocardiographic diagnosis of BAV identified retrospectively: (1) a community
      cohort of 416 patients with first BAV diagnosis (age 35+/-21 years, follow-up
      16+/-7 years), (2) a tertiary clinical referral cohort of 2824 BAV adults (age
      51+/-16 years, follow-up 9+/-6 years), and (3) a surgical referral cohort of 2242
      BAV adults referred for aortic valve replacement (AVR) (age 62+/-14 years, follow
      up 6+/-5 years). For the community cohort, 20-year risks of aortic regurgitation
      (AR), AVR, and infective endocarditis were higher in men (all P<=0.04); for a
      total BAV-related morbidity risk of 52+/-4% vs 35+/-6% in women (P=0.01). The
      cohort's 25-year survival was identical to that in the general population
      (P=0.98). AR independently predicted mortality in women (P=0.001). Baseline AR
      was more common in men (P<=0.02) in the tertiary cohort, with 20-year survival
      lower than that in the general population (P<0.0001); age-adjusted relative death
      risk was 1.16 (95% confidence interval [CI] 1.05-1.29) for men versus 1.67 (95%
      CI 1.38-2.03) for women (P=0.001). AR independently predicted mortality in women
      (P=0.01). Baseline AR and infective endocarditis were higher in men (both
      <=0.001) for the surgical referral cohort, with 15-year survival lower than that
      in the general population (P<0.0001); age-adjusted relative death risk was 1.34
      (95% CI 1.22-1.47) for men versus 1.63 (95% CI 1.40-1.89) for women (P=0.026). AR
      and NYHA class independently predicted mortality in women (both P<=0.04).
      CONCLUSIONS: Within evolving echocardiographic-clinical stages, the long-term
      survival of adults with BAV is not benign, as both men and women incur excess
      mortality. Although BAV-related morbidity is higher in men in the community, and
      AR and infective endocarditis are more prevalent in men, women exhibit a
      significantly higher relative risk of death in tertiary and surgical referral
      cohorts, which is independently associated with AR.

PMID- 27688240
TI  - How strong is the association between IPF and lung cancer? An answer from
      airway's DNA.
AB  - Idiopathic pulmonary fibrosis is a chronic progressive disease of lung
      interstitium of unknown etiology with poor prognosis. In patients with IPF, the
      incidence of lung cancer is much higher than that in the general population. The
      identification of noninvasive biomarkers for early diagnosis of IPF is of great
      relevance in consideration of the management of these patients. Among the
      noninvasive omic markers, an increasing interest has been directed toward the
      study of genetic alterations of microsatellites (MAs) in exhaled breath
      condensate (EBC). The aim of this preliminary study was to investigate the MAs,
      located in chromosomal regions 8p21.3-q11.1 and 17q11.2-q21, that harbor tumor
      suppressor genes, in EBC and in the paired whole blood (WB) of IPF patients.
      Eleven IPF patients were compared with 10 healthy control subjects. All subjects
      underwent collection of the EBC and WB. The EBC was collected using a condenser.
      Four microsatellite markers (THRA1, D17S579, D17S250 and D8S137) were used for
      the analysis of MAs. The EBC-DNA and WB-DNA were amplified by PCR; PCR products
      were analyzed using the ABI Prism 310 DNA. Microsatellite alterations were found
      in 58.82 % of EBC-DNA and 12.50 % of WB-DNA in patients with IPF (p < 0.01). None
      of the healthy subjects exhibited MAs in the studied markers. Our findings
      suggest that these genetic alterations, studied in EBC, may play an important
      role in the complex genetic basis of IPF. Since these MAs are frequently detected
      in cancer, they might explain the higher relative risk of tumorigenesis in this
      disease. 

PMID- 27688241
TI  - Expression of Ezrin and Estrogen Receptors During Cervical Carcinogenesis.
AB  - RATIONALE: Development of cervical squamous carcinoma (CXCA) is accompanied by
      changes in estrogen receptors (ERs, ERalpha and ERbeta) and ezrin expression;
      however, reports have been conflicting. Using histologically documented staging
      of cervical biopsies, we determined ezrin and ER relationships during CXCA
      development. METHODS: Immunoreactive (ir) ezrin, ir-ERalpha, and ir-ERbeta were
      studied in normal epithelium, carcinoma in situ/cervical intraepithelial
      neoplasia (CIN) 1 to 3, and local invasion or metastatic CXCA. Results were
      compared using H scoring. Cultures of Caski metastatic CXCA cells were treated
      with estradiol and/or tamoxifen and studied for ER-driven ir-ezrin and the
      morphologic response. RESULTS: Koilocytosis was present and indicated viral
      presence. The ezrin H score increased from CIN1 to CIN3, reaching significant
      differences from normal by CIN3 ( P = .004) and 2* normal in metastatic CXCA.
      Estrogen receptor alpha and ERbeta H scores fell, reaching significance by CIN3
      (ERalpha, P = .0001; ERbeta, P = .024). During estradiol treatment, ezrin in
      Caski cells increased and localized to the periphery, in ruffles and processes.
      The selective ER modulator tamoxifen blocked the estradiol-induced changes.
      CONCLUSIONS: During cervical carcinogenesis, the usual relationship between
      estrogen and ezrin induction is abridged. This is consistent with the effects of
      human papilloma virus viral proteins such as E6 and E7 that upregulate SIX1, a
      protein that induces ezrin. Cervical carcinogenesis is progressive but arrests at
      the preinvasive stage for varying lengths of time. These studies suggest that
      changes in ezrin may be associated with the development of the invasive phenotype
      and penetration of the basement membrane. They also raise the possibility that
      inhibiting ezrin expression could be a target for the prevention of invasive
      CXCA.

PMID- 27688239
TI  - Expression of the anaphylatoxin C5a receptor in gastric cancer: implications for
      vascular invasion and patient outcomes.
AB  - The C5a receptor (C5aR) expressed in various types of cancers is involved in C5a
      induced cancer cell invasion. However, its role in gastric cancer has not yet
      been fully elucidated. Therefore, we studied the clinical significance of C5aR
      expression in gastric cancer. The association of C5aR expression in gastric
      cancer, determined by immunostaining using the anti-C5aR antibody, with
      clinicopathological parameters and outcomes was evaluated in 148 patients.
      Further, the association of C5aR expression in liver metastatic sites with
      clinicopathological parameters was investigated in a separate cohort of 58
      patients who underwent hepatectomy. High tumoral C5aR expression (n = 45, 30.4 %)
      was significantly related to tumor location, cancer invasion depth, vascular and
      lymphatic invasion, and tumor stage. The 5-year recurrence-free and overall
      survival rates of patients with high tumoral C5aR expression were significantly
      lower than those of patients with low tumoral C5aR expression (50.9 vs. 84.2 %, P
      = 0.002 and 58.8 vs. 86.1 %, P = 0.007, respectively). The incidence of liver
      metastasis was significantly higher in patients with high tumoral C5aR expression
      (13.3 %) than in those with low tumoral C5aR expression (3.9 %; P = 0.04). C5aR
      expression at liver metastatic sites was associated with the C5aR expression
      status at the primary site (P = 0.0004), vascular invasion at the primary site (P
      = 0.04), and tumor size at the metastatic site (P = 0.01). C5aR expression in
      gastric cancer was associated with cancer progression, liver metastasis, and poor
      prognosis. Therefore, C5aR may represent a prognostic factor and therapeutic
      target in gastric cancer. 

PMID- 27688242
TI  - Both the Suprachiasmatic Nucleus and the Superior Ovarian Nerve Contribute to the
      Processes of Ovulation and Steroid Hormone Secretion on Proestrus.
AB  - The aims of the present study were to analyze if the superior ovarian nerve (SON)
      plays a role in the neural signals from suprachiasmatic nucleus (SCN) that lead
      to ovulation and ovarian steroids secretion on proestrus day. Rats on proestrus
      day were treated at 11.00 to 11.30 or 17.00 to 17.30 hours with 1 of the 3
      experimental procedures (1) unilateral or bilateral SON sectioning, (2)
      unilateral or bilateral injury to the SCN, or (3) unilateral injury to the SCN
      followed by unilateral sectioning of the SON ipsilateral to the treated SCN.
      Treatments were evaluated 24 hours after surgical procedures. Compared to
      laparotomized animals, right or bilateral SON sectioning treatment at 17.00 hours
      resulted in lower ovulation rates and number of ova shed by the right ovary. The
      ovaries of nonovulating animals showed early follicular luteinization signs and
      trapped ova. Bilateral SCN injury treatment at 11.00 hours resulted in
      anovulation; whereas right SCN injury treatment, with or without right SON
      sectioning, resulted in a lower number of ova shed. Injecting luteinizing hormone
      releasing hormone to animals with bilateral SCN injury restored ovulation. In
      rats with unilateral or bilateral SON sectioning, or with injury to the SCN with
      or without unilateral sectioning of the SON, the effects on hormone levels
      depended of the hormone studied and the time of day treatment was performed. The
      present results suggest that on proestrus day, the role of the right or both SON
      in ovulation and steroid hormone secretion regulation takes place through
      different neuroendocrine mechanisms from SCN.

PMID- 27688243
TI  - Follicular Volume Predicts Oocyte Maturity: A Prospective Cohort Study Using
      Three-Dimensional Ultrasound and SonoAVC.
AB  - The aim of this study was to investigate whether the automatic measurement of
      follicular volume by three-dimensional (3D) ultrasound can predict the number of
      mature oocytes retrieved. A prospective cohort study including 47 women
      undergoing in vitro fertilization was conducted in a private fertility center.
      Follicular growth was monitored both manually and automatically using 3D scanning
      with SonoAVC on the day of human chorionic gonadotropin (hCG) administration.
      Regression analysis showed that under a standard protocol for hCG administration,
      the count of mature oocytes is well predicted by a multivariate model including
      the counts of follicles in the volume classes 2.00 to 5.00 cm3, 1.50 to 1.99 cm3,
      1.00 to 1.49 cm3, and 0.60 to 0.99 cm3 In conclusion, this study shows that
      follicular volume as measured by SonoAVC on the day of hCG administration can be
      useful to predict oocyte maturity. Specifically, larger follicles and smaller
      size follicles (class 0.60-0.99 cm3) contribute to the mature oocyte count. This
      finding warrants the design of clinical trials to establish new criteria for hCG
      administration based on follicular volume.

PMID- 27688244
TI  - Endometriosis-Derived Thromboxane A2 Induces Neurite Outgrowth.
AB  - Hyperinnervation in endometriosis is now well documented, but so far only a few
      neurotrophins have been identified. Since endometriotic stromal cells secrete
      thromboxane A2 (TXA2), we sought to determine whether TXA2, derived from
      endometriotic stromal cells, induces neurite outgrowth. Using primary sensory
      neurons derived from rat dorsal root ganglia (DRG) and ectopic endometrial
      stromal cells (EESCs) derived from human ovarian endometrioma tissues, we treated
      the primary neurons with different concentrations of U-46619, a stable TXA2
      mimetic, and performed a neuronal growth assay. The primary neurons were also
      cocultured with a vehicle, nerve growth factor (NGF, serving as a positive
      control), the supernatant of EESC culture medium, or the supernatant of EESCs
      pretreated with ozagrel, a thromboxane synthase inhibitor, and a neuronal growth
      assay was performed. The total neurite length was evaluated through
      immunofluorescence microscopy. We found that U-46619 significantly increased the
      neurite outgrowth in DRG neurons in a concentration-dependent fashion ( P <
      .001). It also increased the number of neurite ends in a concentration-dependent
      fashion. Ozagrel treatment alone had no effect on the neurite growth ( P > .05),
      and the treatment with the supernatant of EESCs induced neurite outgrowth just as
      potently as that treated with NGF (positive control; P > .05). Remarkably,
      treatment with the EESC supernatant increased the neurite outgrowth by nearly 3
      fold as compared with the control ( P < .01), but the pretreatment with ozagrel
      abolished the stimulatory effect of the EESC by 31.3% ( P < .05). These findings
      indicate that EESCs potently induce neurite outgrowth, and endometriosis-derived
      TXA2 is responsible, at least in part, for this neurotrophic effect.

PMID- 27688245
TI  - When a Baby Dies: A Systematic Review of Experimental Interventions for Women
      After Stillbirth.
AB  - OBJECTIVES: To identify and evaluate intervention studies (ie, experimental study
      in which the participants undergo some kind of intervention in order to evaluate
      its impact) that target mental and/or physical health outcomes in women who have
      experienced stillbirth and to provide specific recommendations for future
      research and intervention work. METHODS: A librarian conducted an initial search
      using CINAHL, Cochrane Library, PsycInfo, PubMed, SocIndex, and Web of Knowledge
      in the spring of 2016. Reference mining provided further articles. Articles were
      eligible if they were: (1) published in English, (2) published in a peer-reviewed
      journal, (3) published in 1980 or later, (4) an intervention that evaluated
      (qualitative or quantitative methods) mental and/or physical health, and (5)
      included women who had experienced a stillbirth (in utero fetal death at >=20
      weeks of gestation). RESULTS: The combined searches produced 2733 articles
      (including duplicates). After duplicate articles were removed (n = 928), the
      research team screened the titles, abstracts, and full texts (when necessary) for
      eligibility (n = 1805). Two articles were identified that met our eligibility
      criteria. Conclusion for Practice: There is a lack of intervention research in
      women with stillbirth. It is imperative to develop and implement interventions to
      improve both mental and physical health in this population, especially in the
      interconception period (ie, stillbirth aftercare). Future intervention research
      is needed to determine appropriate support and efficacious delivery of support
      interventions, feasibility and effectiveness of physical activity interventions
      and complementary approaches, appropriate timing and dose of interventions, and
      culturally sensitive interventions appropriate for racial/ethnic minority women
      with stillbirth.

PMID- 27688246
TI  - Adiponectin: possible link between metabolic stress and oxidative stress in the
      elderly.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationships between the
      serum levels of adiponectin and systemic oxidative stress exerted on lipids,
      proteins, as well as endothelial function and cardiovascular diseases (CVD) risk
      markers, in elderly subjects with metabolic syndrome (MS). METHODS: The serum
      advanced glycation and oxidation protein products, low-density lipoprotein
      susceptibility to oxidation (oxLDL), nitric oxide metabolic pathway products
      (NOx), serum lipid peroxidation, as well as total antioxidant/oxidative capacity
      (TAC/TOC), were analyzed in elderly subjects with MS (n = 44), compared to aged
      matched control (n = 39). RESULTS: We pointed out significantly lower levels of
      adiponectin in elderly MS subjects concomitantly with significantly higher levels
      of oxidative stress and CVD risk markers. Significant positive correlations were
      found between serum adiponectin levels and HDL-cholesterol (p < 0.05) and the
      total cholesterol/LDL-cholesterol ratio (p < 0.01). Additionally, adiponectin
      levels were significantly inversely associated with insulin resistance index
      (HOMA-IR, r = -0.348; p < 0.05) and serum lipid peroxidation (r = -0.337; p <
      0.05), and significantly positively with the antioxidant capacity (TAC, r =
      0.339; p < 0.05). Conversely, adiponectin levels were significantly negatively (r
      = -0.310; p < 0.05) associated with serum uric acid concentration. CONCLUSIONS:
      The major protective role of adiponectin versus stress related to an impaired
      glucose and lipid metabolism suggests that adiponectin plays a critical role in
      adiposity-related metabolic stress and redox homeostasis.

PMID- 27688248
TI  - Synergistic protective effect of paeoniflorin and beta-ecdysterone against
      rotenone-induced neurotoxicity in PC12 cells.
AB  - There are several factors, like oxidative stress and neurons loss, involving
      neurodegenerative diseases such as Parkinson's disease (PD). The combination of
      antioxidant and anti-apoptotic agent is becoming a promising approach to fight
      against PD. This study evaluates the hypothesis that paeoniflorin (PF) and beta
      ecdysterone (beta-Ecd) synergize to protect PC12 cells against toxicity induced
      by PD-related neurotoxin rotenone. The combination of PF and beta-Ecd, hereafter
      referred to as the PF/beta-Ecd, at suboptimal concentrations increased the
      viability of rotenone-exposed PC12 cells in a synergistic manner. PF and beta-Ecd
      cooperate to attenuate the rotenone-induced apoptosis by decrease in Bax
      expression, caspase-9 activity, and caspase-3 activity. PF or PF/beta-Ecd, but
      not beta-Ecd, inhibited rotenone-triggered protein kinase C-deltakinase C-delta
      (PKCdelta) upregulation and nuclear factor kappaB (NF-kappaB) activation. beta
      Ecd or PF/beta-Ecd, but not PF, enhanced serine/threonine protein kinase (Akt)
      activation, promoted nuclear factor E2-related factor 2 (Nrf2) nuclear
      accumulation, suppressed reactive oxygen species (ROS) production.
      Neuroprotection of PF/beta-Ecd could be completely blocked by PKCdelta inhibitor
      rottlerin plus Akt specific inhibitor LY294002. Dual blockade of the PKCdelta/NF
      kappaB pathway by PF and activation of Akt/Nrf2 pathway by beta-Ecd results in a
      synergistic neuroprotective effect against rotenone-induced neurotoxicity in
      vitro. These findings provide the rationale for determining the in vivo activity
      of combined therapy with PF and beta-Ecd against PD.

PMID- 27688247
TI  - Higher levels of different muscarinic receptors in the cortex and hippocampus
      from subjects with Alzheimer's disease.
AB  - It has been suggest that drugs specifically targeting muscarinic receptors will
      be useful in treating Alzheimer's disease. We decided to determine if the
      response to such drugs may be altered, because of changes in the levels of
      muscarinic receptors in the CNS from subjects with the disorder. We used in situ
      radioligand binding with autoradiography to measure the levels of [3H]pirenzepine
      binding to muscarinic M1 receptors, [3H]AF-DX 386 binding to muscarinic M1, M2,
      and M4 receptors, and [3H]4-DAMP binding to muscarinic M1 and M3 receptors in the
      dorsolateral prefrontal cortex and hippocampus from subjects with Alzheimer's and
      age/sex-matched controls. Compared with controls, [3H]pirenzepine binding was
      higher in the dentate gyrus from subjects with Alzheimer's disease. [3H]AF-DX 386
      binding was higher in the subiculum and parahippocampal gyrus from subjects with
      the disorder. In Alzheimer's disease, [3H]-DAMP binding was higher in the
      dorsolateral prefrontal cortex but not different in the hippocampus. Our data
      show complex changes in the levels of muscarinic receptors in the CNS from
      subjects with Alzheimer's disease which may affect clinical response to treatment
      with drugs-targeting these receptors.

PMID- 27688250
TI  - Engaging research participants to inform the ethical conduct of mobile imaging,
      pervasive sensing, and location tracking research.
AB  - Researchers utilize mobile imaging, pervasive sensing, social media, and location
      tracking (MISST) technologies to observe and intervene with participants in their
      natural environment. The use of MISST methods and tools introduces unique ethical
      issues due to the type and quantity of data, and produces raising new challenges
      around informed consent, risk assessment, and data management. Since MISST
      methods are relatively new in behavioral research, there is little documented
      evidence to guide institutional review board (IRB) risk assessment and inform
      appropriate risk management strategies. This study was conducted to contribute
      the participant perspectives when considering ethical and responsible practices.
      Participants (n = 82) enrolled in an observational study where they wore several
      MISST devices for 1 week completed an exit survey. Survey items focused on the
      following: 1-device comfort, 2-informed consent, 3-privacy protections, and 4
      bystander engagement. The informed consent process reflected participant actual
      experience. Device comfort and privacy were raised as concerns to both the
      participants and bystanders. While the majority of the participants reported a
      positive experience, it is important to note that the participants were
      volunteers who were not mandated to wear tracking devices and that persons who
      are mandated may not have a similar response. Findings support strategies
      proposed in the Kelly et al. (2013) ethical framework, which emphasizes
      procedures to improve informed consent, protect privacy, manage data, and respect
      bystander rights when using a wearable camera.

PMID- 27688251
TI  - Cultural Influences on Primary Care Delivery.

PMID- 27688249
TI  - Implementation evaluation of the Telephone Lifestyle Coaching (TLC) program:
      organizational factors associated with successful implementation.
AB  - The Telephone Lifestyle Coaching (TLC) program provided telephone-based coaching
      for six lifestyle behaviors to 5321 Veterans at 24 Veterans Health Administration
      (VHA) medical facilities. The purpose of the study was to conduct an evaluation
      of the TLC program to identify factors associated with successful implementation.
      A mixed-methods study design was used. Quantitative measures of organizational
      readiness for implementation and facility complexity were used to purposively
      select a subset of facilities for in-depth evaluation. Context assessments were
      conducted using interview transcripts. The Consolidated Framework for
      Implementation Research (CFIR) was used to guide qualitative data collection and
      analysis. Factors most strongly correlated with referral rates included having a
      skilled implementation leader who used effective multi-component strategies to
      engage primary care clinicians as well as general clinic structures that
      supported implementation. Evaluation findings pointed to recommendations for
      local and national leaders to help anticipate and mitigate potential barriers to
      successful implementation.

PMID- 27688252
TI  - Capsule Commentary on Wong et al., Patient-Centered Medical Home Implementation
      in the Veterans Health Administration and Primary Care Use: Differences by
      Patient Comorbidity Burden.

PMID- 27688253
TI  - Frustrated Patients and Fearful Physicians.

PMID- 27688254
TI  - Limited Influence of Urban Stormwater Runoff on Salt Marsh Platform and Marsh
      Creek Oxygen Dynamics in Coastal Georgia.
AB  - Oxygen concentrations and oxygen utilization rates were monitored continuously
      for 23 months on marsh platforms and in small tidal creeks at two sites in
      coastal Georgia, USA, that receive urban stormwater runoff via an extensive
      network of drainage canals. These data were compared to nearby control sites that
      receive no significant surface runoff. Overall, rainfall and runoff per se were
      not associated with differences in the oxygen dynamics among the different
      locations. Because of the large tidal range and long tidal excursions in coastal
      Georgia, localized inputs of stormwater runoff are rapidly mixed with large
      volumes of ambient water. Oxygen concentrations in tidal creeks and on flooded
      marsh platforms were driven primarily by balances of respiration and
      photosynthesis in the surrounding regional network of marshes and open estuarine
      waters. Local respiration, while measurable, was of relatively minor importance
      in determining oxygen concentrations in tidal floodwaters. Water residence time
      on the marshes could explain differences in oxygen concentration between the
      runoff-influenced and control sites.

PMID- 27688255
TI  - A Large-Scale, Multiagency Approach to Defining a Reference Network for Pacific
      Northwest Streams.
AB  - Aquatic monitoring programs vary widely in objectives and design. However, each
      program faces the unifying challenge of assessing conditions and quantifying
      reasonable expectations for measured indicators. A common approach for setting
      resource expectations is to define reference conditions that represent areas of
      least human disturbance or most natural state of a resource characterized by the
      range of natural variability across a region of interest. Identification of
      reference sites often relies heavily on professional judgment, resulting in
      varying and unrepeatable methods. Standardized methods for data collection, site
      characterization, and reference site selection facilitate greater cooperation
      among assessment programs and development of assessment tools that are readily
      shareable and comparable. We illustrate an example that can serve the broader
      global monitoring community on how to create a consistent and transparent
      reference network for multiple stream resource agencies. We provide a case study
      that offers a simple example of how reference sites can be used, at the landscape
      level, to link upslope management practices to a specific in-channel response. We
      found management practices, particularly areas with high road densities, have
      more fine sediments than areas with fewer roads. While this example uses data
      from only one of the partner agencies, if data were collected in a similar manner
      they can be combined and create a larger, more robust dataset. We hope that this
      starts a dialog regarding more standardized ways through inter-agency
      collaborations to evaluate data. Creating more consistency in physical and
      biological field protocols will increase the ability to share data.

PMID- 27688256
TI  - Using Different Grazing Practices for Increasing Plant Biodiversity in the Dykes
      and Embankments Along the Rhone River (Southern France).
AB  - Extensive grazing by domestic herbivores is a widespread management practice used
      since the 80s in many European agro-ecosystems such as semi-natural grasslands to
      maintain open habitats and to enhance biodiversity. Such grazing systems have
      principally been tested in cultural ecosystems of high nature value threatened by
      grazing abandonment. However, there have been few case studies of grazing
      management in very anthropized ecosystems, such as the new ecosystems created by
      urban or industrial conversions. In Southern France, the Rhone channeling for
      navigation and electricity production generated in the 1950s the construction of
      thousands of hectares of dams and dykes which were colonized naturally by diverse
      plant communities. Yet shrub encroachment and the consequent recourse to
      mechanical cutting to facilitate control and maintenance, raise the question of
      how best to maintain and manage these new habitats. Consequently, since 1999,
      different low-intensity grazing management systems using rustic breeds of cattle,
      horses and goats have been tested on a protected reserve of 1454 ha located in
      the lower part of the Rhone river. Extensive grazing, more than cutting or no
      management, positively modified vegetation heterogeneity (beta-diversity), the
      target open grassland species, but not plant species richness (alpha-diversity).
      However, the current monitoring shows that these benefits of grazing will be
      confirmed only if low-intensity grazing systems are sustained and if new
      adaptations can be also made, such as the use of mixed stocking and the
      establishment of multiyear contracts with breeders.

PMID- 27688257
TI  - Cranes and Crops: Investigating Farmer Tolerances toward Crop Damage by
      Threatened Blue Cranes (Anthropoides paradiseus) in the Western Cape, South
      Africa.
AB  - The Western Cape population of Blue Cranes (Anthropoides paradiseus) in South
      Africa is of great importance as the largest population throughout its range.
      However, Blue Cranes are strongly associated with agricultural lands in the
      Western Cape, and therefore may come into conflict with farmers who perceive them
      as damaging to crops. We investigated the viability of this population by
      exploring farmer attitudes toward crane damage in two regions of the Western
      Cape, the Swartland and Overberg, using semi-structured interviews. Perceptions
      of cranes differed widely between regions: farmers in the Swartland perceived
      crane flocks to be particularly damaging to the feed crop sweet lupin (65 % of
      farmers reported some level of damage by cranes), and 40 % of these farmers
      perceived cranes as more problematic than other common bird pests. Farmers in the
      Overberg did not perceive cranes as highly damaging, although there was concern
      about cranes eating feed at sheep troughs. Farmers who had experienced large
      flocks on their farms and farmers who ranked cranes as more problematic than
      other bird pests more often perceived cranes to be damaging to their livelihoods.
      Biographical variables and crop profiles could not be related to the perception
      of damage, indicating the complexity of this human-wildlife conflict. Farmers'
      need for management alternatives was related to the perceived severity of damage.
      These results highlight the need for location-specific management solutions to
      crop damage by cranes, and contribute to the management of this vulnerable
      species.

PMID- 27688259
TI  - Pre-hospital identification and post-recovery challenges of intoxication with
      synthetic cannabinoid containing legal high products such as 'Exodus Damnation'.
AB  - This short report describes the case of a young adult male who had smoked a
      synthetic cannabinoid legal high product called 'Exodus Damnation'. The patient's
      presentation was atypical from that described in the literature, with hypotension
      and hypoxaemia. Of note was the rapid recovery after pre-hospital intervention
      with high-flow oxygen therapy and intravenous fluids. The patient refused on
      going care, despite repeated advice to attend the Emergency Department. The
      distinct lack of specialist support and referral to drug treatment for this
      patient population, with whom ambulance services are coming into contact with
      increasing frequency, is reported. For those patients with the capacity to refuse
      on-going care, ambulance services may be in an opportune position to actively
      promote referral to support services for these vulnerable individuals.

PMID- 27688258
TI  - Quantitation of isobaric phosphatidylcholine species in human plasma using a
      hybrid quadrupole linear ion-trap mass spectrometer.
AB  - Phosphatidylcholine (PC) species in human plasma are used as biomarkers of
      disease. PC biomarkers are often limited by the inability to separate isobaric
      PCs. In this work, we developed a targeted shotgun approach for analysis of
      isobaric and isomeric PCs. This approach is comprised of two MS methods: a
      precursor ion scanning (PIS) of mass m/z 184 in positive mode (PIS m/z +184) and
      MS3 fragmentation in negative mode, both performed on the same instrument, a
      hybrid triple quadrupole ion-trap mass spectrometer. The MS3 experiment
      identified the FA composition and the relative abundance of isobaric and sn-1, sn
      2 positional isomeric PC species, which were subsequently combined with absolute
      quantitative data obtained by PIS m/z +184 scan. This approach was applied to the
      analysis of a National Institute of Standards and Technology human blood plasma
      standard reference material (SRM 1950). We quantified more than 70 PCs and
      confirmed that a majority are present in isobaric and isomeric mixtures. The FA
      content determined by this method was comparable to that obtained using GC with
      flame ionization detection, supporting the quantitative nature of this MS method.
      This methodology will provide more in-depth biomarker information for clinical
      and mechanistic studies.

PMID- 27688260
TI  - Echocardiographic associates of atrial fibrillation in end-stage renal disease.
AB  - Background: The prevalence of atrial fibrillation (AF) in end-stage renal disease
      (ESRD) patients is relatively high. The present study evaluated the association
      between left atrial (LA) remodelling, including an increased size and myocardial
      fibrosis, and slow LA conduction and the occurrence of AF. Methods: In 171 ESRD
      patients enrolled in the Implantable Cardioverter Defibrillators in Dialysis
      patients (ICD2) trial, the LA dimensions, LA conduction delay [as reflected by
      the time difference between P-wave onset on surface electrocardiogram and A'-wave
      on tissue Doppler imaging (PA-TDI)] and LA function were compared between
      patients who exhibited AF versus patients without AF. Based on ICD remote
      monitoring or clinical records, the occurrence of AF was detected. Results: Of
      171 patients, 47 (27%) patients experienced AF. Despite comparable left
      ventricular ejection fraction and prevalence of significant mitral regurgitation,
      patients with AF had significantly larger LA volume index (mean +/- standard
      deviation) (29 +/- 11 versus 23 +/- 10 mL/m2, P = 0.001), longer PA-TDI duration
      (144 +/- 30 versus 131 +/- 27 ms, P = 0.010) and reduced late diastolic mitral
      annular velocity (A') (7.1 +/- 2.8 versus 8.2 +/- 2.4 cm/s, P = 0.012) compared
      with patients without AF. On multivariable analysis, larger LA volume index [odds
      ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08, P = 0.017], longer PA
      TDI duration (OR 1.02, 95% CI 1.00-1.03, P = 0.025) and reduced A' (OR 0.84, 95%
      CI 0.72-0.98, P = 0.025) were independently associated with AF after adjusting
      for age and left ventricle diastolic relaxation. Conclusion: ESRD patients with
      AF show more advanced changes in the LA substrate than ESRD patients without AF.

PMID- 27688261
TI  - Optical Coherence Tomography Predictors for Edge Restenosis After Everolimus
      Eluting Stent Implantation.
AB  - BACKGROUND: Stent edge restenosis (SER) remains a potential limitation of drug
      eluting stents. The aim of this study was to determine optical coherence
      tomography (OCT) predictors for angiographic late SER after everolimus-eluting
      stent implantation. METHODS AND RESULTS: We retrospectively analyzed 319 patients
      who underwent OCT immediately after everolimus-eluting stent implantation and
      scheduled 9- to 12-month follow-up angiography. The binary angiographic SER rate
      was 10% (32/319) in the patients, 8.4% (32/382) in lesions, and 4.4% (33/744) in
      stent edge segments. In the stent edge segments at post stenting, OCT-derived
      lipidic plaque (61% versus 20%; P<0.001) was more often observed in the SER
      group, and OCT-measured minimum lumen area (4.13+/-2.61 versus 5.58+/-2.46 mm2;
      P=0.001) was significantly smaller in the SER group compared with the non-SER
      group. Multivariate analysis identified lipidic plaque (odds ratio: 5.99; 95%
      confidence interval: 2.89-12.81; P<0.001) and minimum lumen area (odds ratio:
      0.64; 95% confidence interval: 0.42-0.96; P=0.029) as independent predictors of
      binary SER. Receiver-operating characteristic analysis demonstrated that lipid
      arc of 185 degrees  (sensitivity: 71%; specificity: 72%; area under the curve:
      0.761) and minimum lumen area of 4.10 mm2 (sensitivity: 67%; specificity: 77%;
      area under the curve: 0.787) were optimal cutoff values for predicting ischemia
      driven SER. CONCLUSIONS: The present OCT study demonstrated that lipidic plaque
      and minimum lumen area in the stent edge segments at post stenting were
      associated with late SER after everolimus-eluting stent implantation. OCT
      provides valuable information to determine an appropriate landing zone for stent
      implantation.

PMID- 27688264
TI  - Supercollision cooling effects on the hot photoluminescence emission of graphene.
AB  - We report on hot photoluminescence measurements that show the effects of acoustic
      phonon supercollision processes in the intensity of graphene light emission. We
      use a simple optical method to induce defects on single layer graphene in a
      controlled manner to study in detail the light emission dependence on the sample
      defect density. It is now well accepted that the graphene photoluminescence is
      due to black-body thermal emission from the quasi-equilibrium electrons at a
      temperature well above the lattice temperature. Our results show that as the
      sample defect density is increased the electrons relax energy more efficiently
      via acoustic phonon supercollision processes leading to lower electron
      temperatures and thus lower emission intensities. The calculated intensity
      decrease due to supercollision energy relaxation agrees well with the
      experimental data.

PMID- 27688262
TI  - The Prognostic Effect of MAC30 Expression on Patients With Non-Small Cell Lung
      Cancer Receiving Adjuvant Chemotherapy.
AB  - The purpose of this study was to examine the MAC30 expression in non-small cell
      lung cancer and to evaluate its prognostic value on therapeutic response in
      patients with non-small cell lung cancer receiving postoperative chemotherapy.
      Among a total of 218 retrospective Chinese patients with non-small cell lung
      cancer, 164 patients receiving adjuvant chemotherapy were enrolled in this study.
      Real-time polymerase chain reaction was performed to confirm the expression of
      MAC30 messenger RNA in 32 cases of non-small cell lung cancer tumors with the
      corresponding nontumor lung tissues. The MAC30 protein expression in all
      specimens was analyzed by immunohistochemical staining. Moreover, we assessed the
      correlation of MAC30 expression with clinicopathological features, therapeutic
      response, and survival of patients. Here, we observed the increased expression of
      MAC30 messenger RNA in patients with non-small cell lung cancer compared to those
      in control samples. The overexpression of MAC30 was strongly associated with poor
      tumor differentiation, high tumor-node-metastasis stage, and lymph node
      metastasis. In addition, we observed that patients with increased MAC30
      expression showed gloomy overall survival and disease-free survival. A
      multivariate analysis explicated that higher MAC30 expression was a valuable
      independent prognostic factor of poorer tumor differentiation, shorter overall
      survival, and disease-free survival in patients receiving chemotherapy. MAC30
      could be a useful biomarker of tumor differentiation and outcome of patients with
      non-small cell lung cancer. Overexpression of MAC30 predicts a worse tumor
      differentiated stage and prognosis in patients with non-small cell lung cancer
      receiving adjuvant chemotherapy.

PMID- 27688265
TI  - Effect of V/III ratio on the structural and optical properties of self-catalysed
      GaAs nanowires.
AB  - The performance of GaAs nanowire (NW) devices depends critically on the presence
      of crystallographic defects in the NWs such as twinning planes and stacking
      faults, and considerable effort has been devoted to understanding and preventing
      the occurrence of these. For self-catalysed GaAs NWs grown by molecular beam
      epitaxy (MBE) in particular, there are in addition other types of defects that
      may be just as important for NW-based optoelectronic devices. These are the point
      defects such as the As vacancy and the Ga antisite occurring due to the
      inherently Ga-rich conditions of the self-catalysed growth. Here we demonstrate
      experimentally the effects of these point defects on the optical properties of
      GaAs/AlGaAs core-shell NWs grown by self-catalysed MBE. The present results
      enable insight into the role of the point defects both on their own and in
      conjunction with crystallographic planar defects.

PMID- 27688263
TI  - Integrating molecular markers into the World Health Organization classification
      of CNS tumors: a survey of the neuro-oncology community.
AB  - Background: Molecular markers provide important biological and clinical
      information related to the classification of brain tumors, and the integration of
      relevant molecular parameters into brain tumor classification systems has been a
      widely discussed topic in neuro-oncology over the past decade. With recent
      advances in the development of clinically relevant molecular signatures and the
      2016 World Health Organization (WHO) update, the views of the neuro-oncology
      community on such changes would be informative for implementing this process.
      Methods: A survey with 8 questions regarding molecular markers in tumor
      classification was sent to an email list of Society for Neuro-Oncology members
      and attendees of prior meetings (n=5065). There were 403 respondents. Analysis
      was performed using whole group response, based on self-reported subspecialty.
      Results: The survey results show overall strong support for incorporating
      molecular knowledge into the classification and clinical management of brain
      tumors. Across all 7 subspecialty groups, >=70% of respondents agreed to this
      integration. Interestingly, some variability is seen among subspecialties,
      notably with lowest support from neuropathologists, which may reflect their roles
      in implementing such diagnostic technologies. Conclusion: Based on a survey
      provided to the neuro-oncology community, we report strong support for the
      integration of molecular markers into the WHO classification of brain tumors, as
      well as for using an integrated "layered" diagnostic format. While membership
      from each specialty showed support, there was variation by specialty in
      enthusiasm regarding proposed changes. The initial results of this survey
      influenced the deliberations underlying the 2016 WHO classification of tumors of
      the central nervous system.

PMID- 27688266
TI  - Race and Religious Beliefs Are Associated With Communication Regarding
      Reproductive Health and Preconception Counseling in Young Women With Diabetes.
AB  - PURPOSE: The purpose of this study was to examine the relationship between
      selected internal and external characteristics and communication (intended and
      actual) with health care providers (HCPs) about reproductive health and
      preconception counseling among adolescent females with diabetes. METHODS: A
      descriptive, correlational design was employed to conduct a secondary analysis of
      baseline data from a multisite, randomized controlled trial. Participants were
      110 female adolescents (92% type 1 diabetes). Analysis included multiple linear
      regression and multivariate binary logistic regression analyses to examine the
      association of internal characteristics (age, race, religion, and religious
      beliefs) and external characteristics (ever sexually active, social support, and
      type of routine HCP). RESULTS: Participants were from 13.3 to 20.0 years of age,
      82% were Caucasian, 80% had never been sexually active, and 58% perceived low to
      moderate amounts of social support. For both internal and external
      characteristics, no significant main effects were found for actual or intended
      communication. For internal characteristics, there was an interaction between
      race and religious beliefs for the probability of actual communication. African
      American women who reported that their religious beliefs did not influence their
      sexual behavior had the lowest probability of actual communication compared to
      all other participants. CONCLUSION: Race and religious beliefs should be
      considered when providing reproductive health information to young women with
      diabetes. Further research with a larger, more diverse sample is warranted. These
      results may be considered for future development of novel interventions with
      targeted messages based on these personal characteristics to empower young women
      to initiate conversations with HCPs about reproductive health and preconception
      counseling.

PMID- 27688268
TI  - Identifying and mapping the polytypes and orientation relationships in ZnO/CdSe
      core-shell nanowire arrays.
AB  - Identifying and mapping the crystalline phases and orientation relationships on
      the local scale in core-shell ZnO nanowire heterostructures are of primary
      importance to improve the interface quality, which governs the performances of
      the nanoscale devices. However, this represents a major difficulty, especially
      when the expected polytypes exhibit very similar properties as in the case of
      CdSe. In the present work, we address that issue in ZnO nanowire heterostructures
      involving a uniform and highly conformal CdSe shell grown by molecular beam
      epitaxy. It is shown by x-ray diffraction and Raman spectroscopy through the
      occurrence of the (1010) and (1011) diffraction peaks and of the [Formula: see
      text] mode at 34 cm-1, respectively, that the CdSe shell is mostly crystallized
      into the wurtzite phase. By using automated crystal phase and orientation mapping
      with precession (ASTAR) in a transmission electron microscope and thus by
      benefiting from highly precise electron diffraction patterns, the CdSe shell is
      found to crystallize also into the minority zinc blende phase. The wurtzite CdSe
      shell is epitaxially grown on the top of ZnO nanowires, and some specific
      orientation relationships are mapped and revealed when grown on their vertical
      sidewalls. Zinc blende CdSe domains are also formed exclusively in the center of
      wurtzite CdSe grains located on the vertical sidewalls; both wurtzite and zinc
      blende CdSe crystalline phases have a strong orientation relationship. These
      findings reveal that ASTAR is a powerful technique to elucidate the structural
      properties on the local scale and to gain a deeper insight into their crystalline
      phases and orientation relationships, which is highly promising for many types of
      semiconducting nanowire heterostructures.

PMID- 27688267
TI  - Vessel perforation during stent retriever thrombectomy for acute ischemic stroke:
      technical details and clinical outcomes.
AB  - BACKGROUND: Vessel perforation during stent retriever thrombectomy is a rare
      complication; typically only single instances have been reported. OBJECTIVE: To
      report on a series of patients whose stent retriever thrombectomy was complicated
      by intraprocedural vessel perforation and discuss its potential mechanisms,
      rescue treatment strategies, and clinical significance. METHODS: Cases with
      intraprocedural vessel perforation, where a stent retriever was used either as a
      primary treatment approach or as a part of a direct aspiration first pass
      technique (ADAPT), were included in the final analysis. Clinical data, procedural
      details, radiographic and clinical outcomes were collected from nine
      participating centers. RESULTS: Intraprocedural vessel perforation during stent
      retriever thrombectomy occurred in 16 (1.0%) of 1599 cases. 63% of
      intraprocedural perforations occurred at distal locations. Endovascular rescue
      techniques (most commonly, intracranial balloon occlusion for tamponade) were
      attempted in 50% of cases. Procedure was aborted without any rescue attempts in
      44% of cases. Mortality during hospitalization and at 3 months was 56% and 63%,
      respectively. 25% of patients achieved good functional outcome at 3 months after
      the procedure. CONCLUSIONS: Intraprocedural perforations during stent retriever
      thrombectomy were rare, but when they occurred were associated with high
      mortality. Perforations most commonly occurred at distal occlusion sites and were
      often characterized by difficulty traversing the occlusion with a microcatheter
      or microwire, or while withdrawing the stent retriever. Nevertheless, 25% of
      patients had a favorable functional outcome, suggesting that in some patients
      with this complication good neurological recovery is achievable.

PMID- 27688273
TI  - The emerging battlefront: Infectious diseases.

PMID- 27688274
TI  - Clinical spectrum, diagnostic criteria, and polymerase chain reaction of aqueous
      humor in viral and toxoplasma detection in Fuchs' uveitis syndrome.
AB  - AIM: The aim of this study is to describe the clinical features and diagnostic
      criteria of Fuchs' uveitis (FU) and to determine whether it has an association
      with virus and toxoplasma in the aqueous humor during cataract surgery. SETTING
      AND DESIGN: This is a prospective, case-control study. MATERIALS AND METHODS:
      Patients with FU (n = 25), anterior uveitis (n = 15), and no uveitis (normal) (n
      = 50) were included based on predefined inclusion and exclusion criteria for all
      three groups. Polymerase chain reaction (PCR) of aqueous humor and serum for
      rubella, herpes simplex virus (HSV), cytomegalovirus (CMV), varicella-zoster
      virus (VZV), and toxoplasma was done using conventional uniplex PCR. STATISTICAL
      ANALYSIS: It was done using SPSS software using Chi-square test for categorical
      variables, and P < 0.05 was considered statistically significant. RESULTS: Ninety
      patients were enrolled in the study in three groups, comparable for age, gender,
      and laterality of ocular involvement. All patients had diffuse keratic
      precipitates in FU group (P = 0001) with none having posterior synechiae (P =
      0.046) which was statistically significant when compared to anterior uveitis
      patients. Iris nodules were noted in one case in both groups. Serum and aqueous
      PCR was negative for detection of VZV, CMV, toxoplasma, and rubella in all
      groups. PCR for HSV was positive in one patient in "normal" group but was not
      statistically significant. CONCLUSION: Our study shows that diagnosis of FU is
      mainly clinical. There appears to be no role of aqueous humor testing for viruses
      by PCR to aid in etiological diagnosis.

PMID- 27688275
TI  - Anterior stromal puncture with staining: A modified technique for preoperative
      reference corneal marking for toric lenses and its retrospective analyses.
AB  - INTRODUCTION: Toric intraocular lenses (IOLs) are an effective way of
      compensating preexisting corneal astigmatism during cataract surgery. To achieve
      success, it is imperative to align the toric IOLs in desired position and
      preoperative reference marking is one among the three important steps for
      accurate alignment. To make the marking procedure simpler and effective, we have
      modified the conventional three-step slit lamp-based technique. MATERIALS AND
      METHODS: Patient is seated in front of the slit lamp and asked to keep the chin
      over chin rest. A 26-gauge bent needle with tip stained by sterile blue ink
      marker is used to make anterior stromal puncture (ASP) at the edges of horizontal
      180 degrees  axis near the limbus. RESULTS: A total of 58 eyes were
      retrospectively evaluated. Mean (+/-SD) IOL deviation on day 1 and day 30 was 5.7
      +/- 6.5 degrees  and 4.7 +/- 5.6 degrees , respectively. Median IOL misalignment
      on day 1 and day 30 was 3 degrees . Redialing of IOL was required in 2 (3.4%)
      eyes only, all of which were performed within 1 week of surgery. In total, 2
      (3.7%) eyes had a residual astigmatism of - 0.5 Dcyl and - 1.0 Dcyl,
      respectively. CONCLUSION: ASP is an effective technique for reference marking,
      technically simpler and can be practiced by most of the surgeons. It avoids the
      necessity of high-end sophisticated machinery and gives a better platform for the
      reference corneal marking along with the benefit of reproducibility and
      simplicity.

PMID- 27688276
TI  - Repair of 50-75% full-thickness lower eyelid defects: Lateral stabilization as a
      guiding principle.
AB  - INTRODUCTION: Repair of large defects of the lower eyelid can be difficult. A
      common procedure performed to address these defects is a Hughes flap. This
      procedure has a number of disadvantages: The eye is closed postoperatively, a
      second stage is required, and the edge of the flap is often erythematous. The
      purpose of this paper is to describe a one-stage procedure for the repair of
      large full-thickness defects of the lower lid as an alternative to a Hughes flap.
      MATERIALS AND METHODS: This is a retrospective study of patients who underwent
      the described procedure. The procedure employs lateral stabilization of the
      posterior lamella with a periosteal strip, medial transposition of the lateral
      posterior lamella for central and medial defects, and a myocutaneous advancement
      flap to stabilize the anterior lamella. RESULTS: A total of 38 patients underwent
      the procedure to reconstruct full-thickness defects of the lower lid ranging from
      50% to 75%. All patients underwent previous Mohs excision of a skin cancer. The
      average follow-up was 5.6 months. Eleven patients (29%) had postoperative
      sequelae, but only two patients (5%) required additional treatment. CONCLUSION:
      Lateral stabilization with a periosteal strip and myocutaneous advancement flap
      is an excellent one-step procedure that avoids many of the complications seen
      with the Hughes procedure and is comparable to other techniques used for the
      reconstruction of subtotal, full-thickness lower lid defects.

PMID- 27688277
TI  - Laser intervention on trabeculo-Descemet's membrane after resistant
      viscocanalostomy: Selective 532 nm gonioreconditioning or conventional 1064 nm
      neodymium-doped yttrium aluminum garnet laser goniopuncture?
AB  - PURPOSE: To compare the results of conventional 1064 nm neodymium-doped yttrium
      aluminum garnet laser goniopuncture (Nd:YAG-GP) and selective 532 nm Nd:YAG laser
      (selective laser trabeculoplasty [SLT])  gonioreconditioning (GR) on trabeculo
      Descemet's membrane in eyes resistant to viscocanalostomy surgery. METHODS:
      Thirty-eight eyes of 35 patients who underwent laser procedure after successful
      viscocanalostomy surgery were included in the study. When postoperative
      intraocular pressure (IOP) was above the individual target, the eyes were
      scheduled for laser procedure. Nineteen eyes underwent 532 nm SLT-GR (Group 1),
      and the remaining 19 eyes underwent conventional 1064 nm Nd:YAG-GP (Group 2).
      IOPs before and after laser (1 week, 1 month, 3 months, 6 months, 1 year, and
      last visit), follow-up periods, number of glaucoma medications, and complications
      were recorded for both groups. RESULTS: Mean times from surgery to laser
      procedures were 17.3 +/- 9.6 months in Group 1 and 13.0 +/- 11.4 months in Group
      2. Mean IOPs before laser procedures were 21.2 +/- 1.7 mmHg in Group 1 and 22.8
      +/- 1.9 mmHg in Group 2 (P = 0.454). Postlaser IOP measurements of Group 1 were
      12.1 +/- 3.4 mmHg and 13.8 +/- 1.7 mmHg in the 1 st week and last visit,
      respectively; in Group 2, these measurements were 13.6 +/- 3.7 mmHg and 14.9 +/-
      4.8 mmHg, respectively. There were statistically significant differences (P <
      0.001) in IOP reduction at all visits in both groups; the results of the two
      groups were similar (P > 0.05). Mean follow-up was 16.6 +/- 6.4 months after SLT
      GR and 18.9 +/- 11.2 months after Nd:YAG-GP. CONCLUSIONS: While conventional
      Nd:YAG-GP and SLT-GR, a novel procedure, are both effective choices in eyes
      resistant to viscocanalostomy, there are fewer complications with SLT-GR. SLT-GR
      can be an alternative to conventional Nd:YAG-GP.

PMID- 27688278
TI  - Burden and depression in primary caregivers of persons with visual impairment.
AB  - CONTEXT: Caregivers who assist persons with visual impairment often neglect their
      needs, resulting in burden and depression. Rehabilitation efforts, directed to
      the disabled, seldom target the caregiver. AIM: To assess burden and depression
      in persons caring for blind individuals. SETTINGS AND DESIGN: This was a cross
      sectional study carried out in the outpatient department of a tertiary-level
      teaching hospital in New Delhi. MATERIALS AND METHODS: Institutional Ethical
      Board approval was obtained and written informed consent too was obtained from
      the participants involved in this study. Persons with best-corrected vision
      <20/200 in the better eye, and their primary caregivers, were recruited. We
      recorded demography, other illness/disability, household income, relationship
      with disabled person, and caregiver burden (Caregiver Burden Scale) and
      depression (Centre for Epidemiologic Studies Depression Scale). STATISTICAL
      ANALYSIS: Statistical analysis was carried out using SPSS version 20 (Released
      2011. Armonk, NY: IBM Corp.); range, average, and standard deviation were
      determined for age, burden, and depression. The association between burden and
      depression was determined using Pearson's correlation; the relationship between
      degree of disability and caregiver burden and depression was determined using
      unpaired t-test; using multiple linear regression, factors were found to be
      statistically significant; significance was taken at P < 0.05. RESULTS: Twenty
      seven (53.0%) men and 24 (47.0%) women had visual impairment. Most caregivers (n
      = 40; 81.6%) were first-degree relatives or a spouse; 32 (65%) had schooling <5
      years; and 29 (59%) were unemployed. Depression ranged from 21 to 52 (average
      43.2 +/- 5.71); it correlated with degree of disability (P = 0.012), household
      income (r = -0.320; P = 0.025), and burden (r = 0.616; P < 0.001). Burden ranged
      from 30 to 73 (average 54.5 +/- 6.73) and correlated with degree of disability (P
      = 0.006). On multiple linear regression, burden predicted depression (r = 0.557;
      P < 0.001). CONCLUSIONS: Caregivers merit community support, financial benefit,
      interventions to diagnose and treat depression, and training in coping. Centers
      that provide disability certification could offer counseling.

PMID- 27688279
TI  - Prevalence of glaucoma in Eastern India: The Hooghly River Glaucoma Study.
AB  - CONTEXT: Glaucoma is the leading cause of global irreversible blindness. No
      recent study with adequate sample size has been carried out to estimate glaucoma
      prevalence in Eastern India. AIMS: The aim of this study was to assess and
      compare the prevalence and types of glaucoma in a rural and urban East Indian
      population. SETTINGS AND DESIGN: The Hooghly River Glaucoma Study (HRGS) is a
      population-based cross-sectional study from West Bengal. A tertiary hospital in
      Kolkata was our urban study center. Our rural study area included 28 contiguous
      villages from the district of Hooghly surrounding the rural base hospital located
      at Dhobapara in village Bakulia. Individuals aged 40 years and above were
      included in this study. SUBJECTS AND METHODS: All subjects underwent a detailed
      ophthalmic examination at our base hospitals including applanation tonometry,
      ultrasound pachymetry, gonioscopy, and frequency doubling technology perimetry.
      Glaucoma was defined using modified International Society of Geographical and
      Epidemiological Ophthalmology criteria. STATISTICAL ANALYSIS USED: Analysis was
      performed using Chi-square test and multiple logistic regression using SPSS.
      RESULTS: Totally, 14,092 individuals participated; 2.7% were detected to have
      glaucoma in rural arm and 3.23% in urban arm (P < 0.001). In urban population,
      2.10% had primary open angle glaucoma (POAG), 0.97% had primary angle closure
      glaucoma (PACG), and 0.15% had secondary glaucoma. In rural population, 1.45% had
      POAG, 1.15% had ACG, and 0.10% had secondary glaucoma. CONCLUSIONS: HRGS is the
      largest population-based glaucoma study in India to date with glaucoma prevalence
      comparable to other landmark Indian studies. POAG was the most common form of
      glaucoma in our study population as well. PACG was more common in this region
      than previously thought.

PMID- 27688280
TI  - To assess surgical outcomes of combined femtosecond laser-assisted cataract
      surgery with 25-gauge vitrectomy surgery at a tertiary eye care center.
AB  - BACKGROUND: The aim of this study was to assess the surgical outcomes of combined
      femtosecond laser-assisted cataract surgery (FLACS) with 25-gauge vitrectomy
      surgery. MATERIALS AND METHODS: A retrospective analysis of 45 patients who
      underwent combined FLACS with 25-gauge vitrectomy surgery. RESULTS: A total
      number of 45 eyes of 45 patients were treated with a mean age of 63.27 years
      (range 45-75). The mean follow-up was 3 months (range 3-12 months). The mean
      preoperative best-corrected visual acuity was 1.47 +/- 0.86. The mean
      postoperative vision was 0.36 +/- 0.36 and 0.275 +/- 0.184 at a paired t-test
      revealed a statistically significant improvement in visual acuity at 1 month (P <
      0.001) and 3 months (P < 0.001). The most common indication for surgery was full
      thickness macular hole (51.1%), vitreous hemorrhage (24.4%), followed by
      epiretinal membrane (17.7%) and rhegmatogenous retinal detachment (4.4%).
      CONCLUSION: Combining FLACS with vitrectomy may be a step toward achieving better
      outcomes when combined CS and vitrectomy is performed.

PMID- 27688281
TI  - A treatment method for chronic suppurative lacrimal canaliculitis using chalazion
      forceps.
AB  - PURPOSE: The purpose of this study is to evaluate the effectiveness of chronic
      suppurative lacrimal canaliculitis treatment using chalazion forceps. PATIENTS
      AND METHODS: A prospective study was performed on consecutive patients who
      accepted the aid of chalazion forceps to treat chronic suppurative lacrimal
      canaliculitis. Two different treatment methods using chalazion forceps were
      performed according to the degree of lacrimal canaliculitis. Postoperatively, the
      patients received 0.5% levofloxacin eye drops four times per day and 0.5 g oral
      levofloxacin tablets once per day for 4 days. The follow-up period was more than
      3 months. Lacrimal irrigation, the condition of the lacrimal punctum, and
      patients' symptoms were carefully evaluated. RESULTS: In total, 32 patients met
      the criteria for chronic suppurative lacrimal canaliculitis. Included were 6
      males and 26 females. Their average age was 51.7 +/- 14.9 years (range; 19-80
      years), and all had unilateral canaliculitis. The mean duration of the symptoms
      was 18.9 +/- 9.8 months (range; 3-48 months). The mean follow-up time was 14.7 +/
      7.8 months. The signs and symptoms resolved completely in all patients within 15
      days, and no recurrence was observed. No patients reported epiphora after the
      treatment. CONCLUSIONS: The use of chalazion forceps is effective in treating
      chronic suppurative lacrimal canaliculitis. The forceps may offer an alternative
      treatment technology in the management of suppurative lacrimal canaliculitis.

PMID- 27688282
TI  - Diagnosis and a minimum effective management for nanophthalmic uveal effusion
      syndrome.

PMID- 27688284
TI  - Interface infectious keratitis following deep anterior lamellar keratoplasty.
AB  - A 32-year-old female patient underwent deep anterior lamellar keratoplasty (DALK)
      in both eyes for advanced keratoconus. She developed an infiltrate in the nasal
      paracentral interface of the left eye. In view of the paracentral location,
      localized epithelial removal/stromal scraping was done and the infiltrate was
      removed using forceps and sent for microbiological assay, which revealed fungal
      filaments. The patient successfully responded to intensive topical antifungal
      therapy with the maintenance of visual acuity. Interface keratitis following DALK
      frequently needs graft lift/interface wash due to deep location, rapid spread and
      poor penetration and efficacy of topical medications. In view of a paracentral
      location, modified debulking with topical therapy resulted in a satisfactory
      outcome in our case thereby avoiding the need for more invasive treatments. 

PMID- 27688283
TI  - Orbital infarction syndrome after multiple percutaneous sclerotherapy sessions
      for facial low-flow vascular malformation: A case report and literature review.
AB  - Vision loss following sclerotherapy for facial vascular malformations (VMs) is a
      rare but detrimental complication. Here, we report a case of an 11-year-old boy
      with acute onset blepharoptosis, ophthalmoplegia, and blindness in his right eye
      after the 14 th sclerotherapy session (percutaneous intralesional injection of
      sodium tetradecyl sulfate) for a right facial low-flow VM without orbital
      involvement. Computed tomography angiography revealed no contrast enhancement in
      the right ophthalmic artery, superior ophthalmic vein, or extraocular muscles. He
      presented with the hallmarks of orbital infarction syndrome: Clear signs of
      anterior and posterior segment ischemia and disrupted arterial flow to the
      extraocular muscles. His blepharoptosis and eye movement improved 4 months later;
      however, he remained blind, and phthisis bulbi developed eventually. Thus,
      sclerotherapy for facial VM-even without orbital involvement--may result in
      severe ocular and orbital complications. 

PMID- 27688285
TI  - IgG4-related intraocular inflammation masquerading as ciliary body melanoma in a
      young girl.
AB  - Immunoglobulin G4 (IgG4-related diseases) affects various tissues and organs of
      the human body. Orbital, adnexal, and scleral inflammations were already reported
      in the medical literature. To the best of our knowledge, we report the first case
      of intraocular IgG4-associated inflammatory mass in the ciliary body mimicking as
      a melanoma in a 23-year-old female from Northeast India. Characteristic
      histopathology, immunohistochemistry in the tissue, protein chemistry, and raised
      serum IgG4 were supportive for the diagnosis. As this newly diagnosed disease has
      multi-organ affection and little is known about its pathogenesis particularly in
      eye and adnexa, the present case will open many challenges in clinico
      pathological diagnosis and research in the future. 

PMID- 27688286
TI  - An unusual case of protruding retro-orbital metallic foreign body.
AB  - A 34-year-old female presented with firecracker injury with curved metallic
      foreign body embedded in the left orbit and protruding out through the upper
      eyelid. The report highlights notable aspects in diagnosis, decision-making, and
      successful removal of this unusual case of retro-orbital foreign body. 

PMID- 27688288
TI  - A rare case of Enterococcus faecalis-induced orbital cellulitis and myositis.
AB  - Orbital cellulitis is an infection of soft tissue behind the orbital septum.
      Common pathogens isolated include Staphylococcus aureus, Staphylococcus
      epidermidis, and Streptococcus pneumoniae. It is a straightforward diagnosis and
      usually responds to empirical treatment without any sequela. We report a case of
      orbital cellulitis caused by Enterococcus faecalis, which was complicated by
      myositis of levator palpebrae superioris. To the best of our knowledge, only one
      case report exists dating way back to 1986. 

PMID- 27688287
TI  - Choroidal neovascular membrane in a treated choroidal hemangioma.
AB  - Association of choroidal neovascular (CNV) membrane with circumscribed choroidal
      hemangioma is rare, and the CNV development after photodynamic therapy (PDT) is
      also rare. Etiopathogenesis of these associations is poorly understood. We noted
      the development of CNV over choroidal hemangioma after PDT therapy in a young
      female patient in our hospital. Temporal association of CNV development after PDT
      treatment points toward the possible side effects of PDT. Repeat injections of
      antivascular endothelial growth factor (ranibizumab) regressed the CNV resulting
      in a favorable visual outcome. 

PMID- 27688289
TI  - Ocular toxicity by seeds of Annona squamosa (custard apple).
AB  - Custard apple seeds have been used in native medicine from time immemorial for
      the management of head lice and skin exfoliation. We report six consecutive
      patients who developed toxic keratoconjunctivitis within 6-12 h of ocular
      exposure to custard apple seeds. The use of topical steroid worsens the toxicity
      and predisposes to the development of microbial keratitis in such cases. Patients
      showed a good response to primary treatment with topical fortified antibiotics
      and lubricants. This case series highlights the need to educate the patients
      regarding the potential toxic effects of the custard seeds and the treating
      physicians about possible deleterious effects on using topical steroid. 

PMID- 27688290
TI  - Comment on: Childhood optic atrophy in biotinidase deficiency.

PMID- 27688291
TI  - Comment on: Role of subconjunctival bevacizumab in primary pterygium surgery.

PMID- 27688292
TI  - Reply to comment: The effect of anterior transposition of the inferior oblique
      muscle on eyelid configuration and function.

PMID- 27688293
TI  - Diagnosing of pelvic vein incompetence using minimally invasive ultrasound
      techniques.
AB  - Background Pelvic vein incompetence is a cause for pelvic pain and recurrent
      varicose veins in women. The gold standard diagnostic method is reflux venography
      involving radiation, nephrotoxic contrast and jugular puncture. Trans-vaginal
      ultrasound (TVU) is increasingly being used as a diagnostic tool for pelvic vein
      incompetence. Methods Fifty women with clinical suspicion of pelvic vein
      incompetence and aged between 18 and 55 years were recruited prospectively over
      two years at a large UK University Teaching Hospital. Trans-vaginal ultrasound
      was performed using a standardised protocol which included assessment of the
      ovarian and internal iliac veins bilaterally in the supine and semi-standing
      position with provocative manoeuvres. Diagnostic readability and inter-observer
      variability was determined. Results Mean (range) age of 43 (23-51). Visibility of
      all four pelvic veins was better in the supine position compared with semi
      standing position (76% vs 64%). Pelvic vein incompetence was identified in 34 of
      50 (68%) women in the supine position compared with 38 of 50 (76%) women in the
      semi-standing position. Pelvic vein incompetence was demonstrated in 35 of 50
      (70%) women with Valsalva manoeuvre. Inter-observer variability was 0.84 (kappa,
      very good agreement, p = 0.001). Conclusion Trans-vaginal ultrasound is effective
      at demonstrating pelvic vein incompetence. All trans-vaginal ultrasound protocols
      should include assessment of pelvic veins in the supine and semi-standing
      position with Valsalva manoeuvre.

PMID- 27688294
TI  - Long-term results of intra-arterial onyx injection for type II endoleaks
      following endovascular aneurysm repair.
AB  - Purpose The aim of this paper is to report our experience of type II endoleak
      treatment after endovascular aneurysm repair with intra-arterial injection of the
      embolizing liquid material, Onyx liquid embolic system. Methods From 2005 to
      2012, we performed a retrospective review of 600 patients, who underwent
      endovascular repair of an abdominal aortic aneurysm. During this period, 18
      patients were treated with Onyx for type II endoleaks. Principal findings The
      source of the endoleak was the internal iliac artery in seven cases, inferior
      mesenteric artery in seven cases and lumbar arteries in four cases. Immediate
      technical success was achieved in all patients and no endoleak from the treated
      vessel recurred. During a mean follow-up of 19 months, no major morbidity or
      mortality occurred, and one-year survival was 100%. Conclusions Treatment of type
      II endoleaks with Onyx is safe and effective over a significant time period.

PMID- 27688295
TI  - Biospecimen Sharing Among Hispanic Women in a Safety-Net Clinic: Implications for
      the Precision Medicine Initiative.
AB  - Biospecimen donation is key to the Precision Medicine Initiative, which pioneers
      a model for accelerating biomedical research through individualized care.
      Personalized medicine should be made available to medically underserved
      populations, including the large and growing US Hispanic population. We present
      results of a study of 140 Hispanic women who underwent a breast biopsy at a
      safety-net hospital and were randomly assigned to receive information and request
      for consent for biospecimen and data sharing by the patient's physician or a
      research assistant. Consent rates were high (97.1% and 92.9% in the physician and
      research assistant arms, respectively) and not different between groups (relative
      risk [RR] = 1.05, 95% confidence interval [CI] = 0.96 to 1.10). Consistent with a
      small but growing literature, we show that perceptions of Hispanics'
      unwillingness to participate in biospecimen sharing for research are not
      supported by data. Safety-net clinics and hospitals offer untapped possibilities
      for enhancing participation of underserved populations in the exciting Precision
      Medicine Initiative.

PMID- 27688296
TI  - Effects of metformin on hyperglycemia in an experimental model of tacrolimus- and
      sirolimus-induced diabetic rats.
AB  - BACKGROUND/AIMS: Metformin (MET) is a first-line drug for type 2 diabetes
      mellitus (DM); its effect on new-onset diabetes after transplantation caused by
      immunosuppressant therapy is unclear. We compared the effects of MET on DM caused
      by tacrolimus (TAC) or sirolimus (SRL). METHODS: DM was induced by injection of
      TAC (1.5 mg/kg) or SRL (0.3 mg/kg) for 2 weeks in rats, and MET (200 mg/kg) was
      injected for 2 more weeks. The effects of MET on DM caused by TAC or SRL were
      evaluated using an intraperitoneal glucose tolerance test (IPGTT) and by
      measuring plasma insulin concentration, islet size, and glucose-stimulated
      insulin secretion (GSIS). The effects of MET on the expression of adenosine
      monophosphate-activated protein kinase (AMPK), a pharmacological target of MET,
      were compared between TAC- and SRL-treated islets. RESULTS: IPGTT showed that
      both TAC and SRL induced hyperglycemia and reduced plasma insulin concentration
      compared with vehicle. These changes were reversed by addition of MET to SRL but
      not to TAC. Pancreatic islet cell size was decreased by TAC but not by SRL, but
      addition of MET did not affect pancreatic islet cell size in either group. MET
      significantly increased GSIS in SRL- but not in TAC-treated rats. AMPK expression
      was not affected by TAC but was significantly decreased in SRL-treated islets.
      Addition of MET restored AMPK expression in SRL-treated islets but not in TAC
      treated islets. CONCLUSIONS: MET has different effects on hyperglycemia caused by
      TAC and SRL. The discrepancy between these drugs is related to their different
      mechanisms causing DM.

PMID- 27688297
TI  - Estimating the Risk of Radiocontrast-Associated Nephropathy.
AB  - Estimates of the incidence of radiocontrast-associated nephropathy vary widely
      and suffer from misclassification of the cause of AKI and confounding. Using the
      Nationwide Inpatient Sample, we created multiple estimates of the risk of
      radiocontrast-associated nephropathy among adult patients hospitalized in the
      United States in 2009. First, we stratified patients according to the presence or
      absence of 12 relatively common diagnoses associated with AKI and evaluated the
      rate of AKI between strata. Next, we created a logistic regression model,
      controlling for comorbidity and acuity of illness, to estimate the risk of AKI
      associated with radiocontrast administration within each stratum. Finally, we
      performed an analysis stratified by the degree of preexisting comorbidity. In
      general, patients who received radiocontrast did not develop AKI at a clinically
      significant higher rate. Adjusted only for the complex survey design, patients to
      whom radiocontrast was and was not administered developed AKI at rates of 5.5%
      and 5.6%, respectively. After controlling for comorbidity and acuity of illness,
      radiocontrast administration associated with an odds ratio for AKI of 0.93 (95%
      confidence interval, 0.88 to 0.97). In conclusion, the risk of radiocontrast
      associated nephropathy may be overstated in the literature and overestimated by
      clinicians. More accurate AKI risk estimates may improve clinical decision-making
      when attempting to balance the potential benefits of radiocontrast-enhanced
      imaging and the risk of AKI.

PMID- 27688299
TI  - Effects of whole-body vibration on neuromuscular performance in individuals with
      spinal cord injury: a systematic review.
AB  - OBJECTIVE: To examine the effects of whole-body vibration on neuromuscular
      performance in people with spinal cord injury and evaluate the safe and effective
      vibration protocols. METHODS: PubMed, EMBASE, CINAHL and PEDro were mainly
      searched for English literatures. Other data sources were ClinicalTrials.gov ,
      Current Controlled Trials and reference lists of all relevant articles. The PEDro
      scale was used to evaluate the methodological quality, and the Oxford Centre for
      Evidence-based Medicine level of evidence was used to assess the level of
      evidence. Basic information and whole-body vibration protocols were extracted by
      two independent researchers. Any disagreements were resolved by the third
      researcher. RESULTS: Of the eight included studies involving 94 individuals with
      spinal cord injury and 24 able-bodied participants, six of them reported
      beneficial effects of whole-body vibration on muscle activation and the other two
      on muscle spasticity. Based on the reviewed studies, an intermittent mode of
      whole-body vibration (frequency: 10-50 Hz; amplitude: 0.6-4 mm) is less likely to
      cause adverse events when applying to spinal cord injury subjects standing on
      platform (knees flexed at 10 degrees -40 degrees ). CONCLUSIONS: The strength of
      evidence is insufficient in supporting the benefits of whole-body vibration on
      neuromuscular performance in individuals with spinal cord injury. The
      intermittent vibration (frequency: 10-50 Hz; amplitude: 0.6-4 mm; knee flexion:
      10 degrees -40 degrees ) may be the possible effective range and have good
      compliance.

PMID- 27688300
TI  - The effect of different gas permeability of packaging on physicochemical and
      microbiological parameters of pork loin storage under high O2 modified atmosphere
      packaging conditions.
AB  - The aim of this study was to determine the influence of different packaging
      materials on meat quality during cold storage. Therefore pork loins (m.
      longissimus thoracis et lumborum) obtained from crossbred pigs (Polish Landrance
      x Duroc, n = 6) were stored at 2 C in modified atmosphere packs (80% O2, 20% CO2)
      in four types of trays, which differ in gas permeability. Physicochemical
      (headspace gas composition, pH, colour, drip loss, cooking loss, shear force, the
      basic composition and fatty acid profile) and microbiological ( Salmonella spp.,
      Escherichia coli, Enterobacteriaceae, total aerobic plates count, total
      psychrotrophic bacteria count, the number of lactic acid bacteria, Pseudomonas
      spp., the general amount of yeast and mold) parameters were monitored for up to
      12 days. At the end of the storage period no differences in most physicochemical
      properties of pork loin due to type of packaging were found, however trays with
      high gas permeability had the greatest impact on total aerobic plates count and
      Pseudomonas spp. growth.

PMID- 27688298
TI  - WNT5A-JNK regulation of vascular insulin resistance in human obesity.
AB  - Obesity is associated with the development of vascular insulin resistance;
      however, pathophysiological mechanisms are poorly understood. We sought to
      investigate the role of WNT5A-JNK in the regulation of insulin-mediated
      vasodilator responses in human adipose tissue arterioles prone to endothelial
      dysfunction. In 43 severely obese (BMI 44+/-11 kg/m2) and five metabolically
      normal non-obese (BMI 26+/-2 kg/m2) subjects, we isolated arterioles from
      subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we
      examined insulin-mediated, endothelium-dependent vasodilator responses and
      characterized adipose tissue gene and protein expression using real-time
      polymerase chain reaction and Western blot analyses. Immunofluorescence was used
      to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin
      mediated vasodilation was markedly impaired in visceral compared to subcutaneous
      vessels from obese subjects (p<0.001), but preserved in non-obese individuals.
      Visceral adiposity was associated with increased JNK activation and elevated
      expression of WNT5A and its non-canonical receptors, which correlated negatively
      with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly
      improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial
      cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS
      phosphorylation (p<0.05). We observed profound vascular insulin resistance in the
      visceral adipose tissue arterioles of obese subjects that was associated with up
      regulated WNT5A-JNK signaling and impaired endothelial eNOS activation.
      Pharmacological JNK antagonism markedly improved vascular endothelial function,
      and may represent a potential therapeutic target in obesity-related vascular
      disease.

PMID- 27688301
TI  - Characteristics of adult smokers presenting to a mind-body medicine clinic.
AB  - Mind-body interventions can improve vulnerabilities that underlie smoking
      behavior. The characteristics of smokers who use mind-body medicine have not been
      explored, preventing the development of targeted interventions. Patients ( N =
      593) presenting to a mind-body medicine clinic completed self-report measures.
      Patients were 67 percent never smokers, 27 percent former smokers, and 6 percent
      current smokers. Current smokers were younger; more likely to be single,
      unemployed, or on disability; and report greater depression symptoms, greater
      pain, and lower social support ( ps < .05).Current smokers who use mind-body
      medicine have unique psychosocial needs that should be targeted in mind-body
      smoking cessation interventions.

PMID- 27688302
TI  - With or Without Langendorff: A New Method for Adult Myocyte Isolation to Be
      Tested With Time.

PMID- 27688303
TI  - Mesenchymal Stem Cells Drive Cardiac Stem Cell Chemotaxis, Proliferation, and
      Phenotype via CXCR4 and cKit Signaling.

PMID- 27688304
TI  - Does Autophagy Mediate Cardiac Myocyte Death During Stress?

PMID- 27688305
TI  - The Future of Onco-Cardiology: We Are Not Just "Side Effect Hunters".

PMID- 27688306
TI  - A Strategy for Genomic Research on Common Cardiovascular Diseases Aiming at the
      Realization of Precision Medicine: Personal Insights and Perspectives.

PMID- 27688307
TI  - Initial Outcomes for the NHLBI K99/R00 Pathway to Independence Program in
      Relation to Long-Standing Career Development Programs: Implications for Trainees,
      Mentors, and Institutions.

PMID- 27688308
TI  - Response by Borges et al to Editorial Regarding Article, "Role of Adiponectin in
      Coronary Heart Disease Risk: A Mendelian Randomization Study".

PMID- 27688309
TI  - St. John's Wort Potentiates anti-Nociceptive Effects of Morphine in Mice Models
      of Neuropathic Pain.
AB  - Objective: In this study, we compared the efficacy of a combination of PKC
      blocker St. John's Wort (SJW) and morphine in mice with painful antiretroviral
      (2,3-dideoxycitidine [ddC]) and chemotherapic (oxaliplatin) neuropathy. Methods:
      Morphine (1 and 5 mg/Kg i.p.), SJW (1 and 5 mg/Kg o.s.), or their combination was
      administered by systemic injection, and antinociception was determined by using
      the hot and cold plate tests. Results: Here we demonstrate the ability of SJW to
      relieve neuropathic pain in mice neuropathic models and a potentiation of
      morphine antinociception in thermal pain. The potentiating effect shown by SJW
      was not secondary to its antinociceptive activity as the increase of the morphine
      antinociceptive effect was produced at a dose (1mg/kg o.s.) devoid of any
      capability to modulate the pain threshold in neuropathic pain mice. Further
      examinations of the SJW main components revealed that hypericin was responsible
      for the potentiating properties whereas flavonoids were ineffective. Conclusions:
      These results show that SJW has notable antinociceptive activity for both
      neuropathic pain models and could be used in neuropathic pain relief alone or in
      combination with morphine. These data support the utility of combination
      SJW/opioid therapy in pain management for antinociceptive efficacy by enhancing
      opioid analgesia.

PMID- 27688310
TI  - Classical Conditioning Fails to Elicit Allodynia in an Experimental Study with
      Healthy Humans.
AB  - Objective: Associative learning has been proposed as a mechanism behind the
      persistence of pain after tissue healing. The simultaneous occurrence of
      nociceptive and non-nociceptive input during acute injury mimics the pairings
      thought to drive classical conditioning effects. However, empirical evidence for
      classically conditioned allodynia is lacking. We aimed to manipulate pain
      thresholds with a classical conditioning procedure that used non-nociceptive
      somatosensory stimuli as conditioned stimuli (CS) and nociceptive stimuli as
      unconditioned stimuli. We also explored the influence of gender, depression,
      anxiety, negative affect, and pain catastrophizing on the main manipulation.
      Design: Thirty-four healthy humans participated in a differential classical
      conditioning procedure that used vibrotactile stimulations at two different
      locations as CS. In an acquisition phase, CS+ was paired with painful thermal
      stimulation, and CS- with nonpainful thermal stimulation. Heat pain threshold was
      assessed during paired heat-CS trials before and after acquisition. A 2 (time: 1
      and 2) x 2 (condition: CS+ and CS-) repeated-measures analysis of variance
      compared pain thresholds before and after acquisition. Exploratory analyses
      explored the influence of gender, depression, anxiety, negative affect, and pain
      catastrophizing. Postexperiment questions investigated participants' awareness of
      the contingencies employed. Results: The classical conditioning procedure did not
      alter pain thresholds. Exploratory analyses did not reveal any influence of
      individual differences. Thirty of the 34 participants were unaware of the
      contingencies between stimuli. Conclusions: The results of this study provide no
      evidence that allodynia can be induced in healthy humans using a classical
      conditioning procedure with simultaneous timing.

PMID- 27688311
TI  - Predictors of Persistent Disability and Back Pain in Older Adults with a New
      Episode of Care for Back Pain.
AB  - Objective: To identify predictors of persistent disability and back pain in older
      adults. Design: Prospective cohort study. Setting: Back pain outcomes using
      longitudinal data registry. Subjects: Five thousand two hundred twenty adults age
      65 years and older with a new primary care visit for back pain. Methods: Baseline
      measurements included: demographics, health, and back pain characteristics. We
      abstracted imaging findings from 348 radiology reports. The primary outcomes were
      the Roland-Morris Disability Questionnaire (RMDQ) and back pain intensity. We
      defined persistent disability as RMDQ of 4/24 or higher at both six and 12 months
      and persistent back pain as pain 3/10 or higher at both six and 12 months.
      Results: There were 2,498 of 4,143 (60.3%) participants with persistent
      disability, and 2,099 of 4,144 (50.7%) had persistent back pain. Adjusted
      analyses showed the following characteristics most strongly predictive of
      persistent disability and persistent back pain: sex, race, worse baseline
      clinical characteristics of back pain, leg pain, back-related disability and
      duration of symptoms, smoking, anxiety symptoms, depressive symptoms, a history
      of falls, greater number of comorbidities, knee osteoarthritis, wide-spread pain
      syndromes, and an index diagnosis of lumbar spinal stenosis. Within the imaging
      data subset, central spinal stenosis was not associated with disability or pain.
      Conclusion: We found that many predictors in older adults were similar to those
      for younger populations.

PMID- 27688312
TI  - Pulsed Radiofrequency Attenuates Complete Freund's Adjuvant-Induced Epigenetic
      Suppression of Potassium Chloride Cotransporter 2 Expression.
AB  - Background: Pulsed radiofrequency (PRF) treatment offers pain relief for patients
      suffering from chronic pain who do not respond well to conventional treatments.
      We tested whether PRF treatment attenuated complete Freund's adjuvant (CFA)
      induced inflammatory pain. Epigenetic modification of potassium-chloride
      cotransporter 2 (KCC2) gene expression was examined to elucidate the potential
      contributing mechanism. Methods: Male Sprague-Dawley rats were injected with CFA
      into the plantar surface of the left hind paw to induce inflammation. PRF (20
      minutes of 500-kHz RF pulses, delivered at a rate of 2 Hz, maximum temperature
      42oC) was delivered to the L5 and L6 anterior primary ramus just distal to the
      intervertebral foramen of adult CFA or saline rats. The hind paw withdrawal
      threshold to von Frey filament stimuli and withdrawal latency to radiant heat
      were determined before and after CFA. Acetyl-histone H3 and H4 was determined by
      chromatin immunoprecipitation in spinal dorsal horn. KCC2 expression was
      determined by Western blot. Inhibitory synaptic function was evaluated by patch
      clamp in lamina II neurons. Results: KCC2 gene expression was suppressed through
      histone hypoacetylation, resulting in decreased efficacy of GABAergic signaling
      in CFA rats. PRF increased histone acetylation and KCC2 expression, partially
      restored the GABA synaptic function, and relieved sensitized pain behavior.
      Conclusion: These findings suggest that PRF might be an alternative therapy for
      inflammatory pain. One of the underlying mechanisms is through modification of
      KCC2, which is an important determinant for the efficacy of inhibitory
      neurotransmission in the spinal cord, and its expression levels are regulated by
      histone acetylation epigenetically following inflammation.

PMID- 27688313
TI  - Pain Treatments for Nursing Home Residents with Advanced Dementia and Substantial
      Impaired Communication: A Cross-Sectional Analysis at Baseline of a Cluster
      Randomized Controlled Trial.
AB  - Objectives: This is a cross-sectional analysis at baseline of a cluster
      randomized controlled trial to identify factors associated with the use of
      pharmacological and nonpharmacological pain treatments by nursing home residents
      with dementia and impaired communication. Methods: One hundred thirty-four
      residents with dementia and impaired communication were recruited. Nine of them
      were excluded because data on their pain treatments were missing, resulting in
      125 for analysis. Hierarchical generalized estimating equations analyses
      controlling for the clustering effect of nursing homes were used to identify
      factors associated with the use of pharmacological and nonpharmacological pain
      treatments. Results: Although all participants had a confirmed pain condition,
      only 23 (18.4%) and 45 (36%) had received pharmacological or nonpharmacological
      pain treatments, respectively. Participants with a higher ability to communicate
      ( P  = 0.031) and fewer pain locations were found to be more likely to receive
      pain medications, with the impact of communication ability being greater among
      participants with better cognitive status than among those with poor cognitive
      status. Participants who had been living in the home longer and who were more
      dependent were less likely to receive nonpharmacological treatments. Conclusion:
      Suboptimal pain management was common among this population. Severe impairment in
      the ability to communicate is a major reason for the underuse of pain
      medications. Staff may become desensitized and fail to perceive subtle changes in
      the residents' behavior as indicative of pain, leading to the underadministering
      of nonpharmacological treatments. To improve this situation, it is suggested that
      observational pain assessments be systematically carried out in nursing homes.

PMID- 27688315
TI  - Complete Genome Sequence of Porcine Sapelovirus Strain USA/IA33375/2015
      Identified in the United States.
AB  - The complete genome of sapelovirus A, formerly known as porcine sapelovirus
      (PSV), from a diarrheic pig was sequenced for the first time in the United States
      (designated PSV USA/IA33375/2015). It shares 87.8% to 83.9% nucleotide identities
      with other reported PSV strains globally and is most closely related to Asia PSV
      strains. 

PMID- 27688314
TI  - Genotype-Dependent and -Independent Calcium Signaling Dysregulation in Human
      Hypertrophic Cardiomyopathy.
AB  - BACKGROUND: Aberrant calcium signaling may contribute to arrhythmias and adverse
      remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may
      distinctly alter calcium handling pathways. METHODS: We analyzed gene expression,
      protein levels, and functional assays for calcium regulatory pathways in human
      HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared
      with control hearts (n=8). RESULTS: Gene expression and protein levels for
      calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban,
      calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII)
      were similar in HCM samples compared with controls. CaMKII protein abundance was
      increased only in sarcomere-mutation HCM (P<0.001). The CaMKII target pT17
      phospholamban was 5.5-fold increased only in sarcomere-mutation HCM (P=0.01), as
      was autophosphorylated CaMKII (P<0.01), suggestive of constitutive activation.
      Calcineurin (PPP3CB) mRNA was not increased, nor was RCAN1 mRNA level, indicating
      a lack of calcineurin activation. Furthermore, myocyte enhancer factor 2 and
      nuclear factor of activated T cell transcription factor activity was not
      increased in HCM, suggesting that calcineurin pathway activation is not an
      upstream cause of increased CAMKII protein abundance or activation. SERCA2A mRNA
      transcript levels were reduced in HCM regardless of genotype, as was sarcoplasmic
      endoplasmic reticular calcium ATPase 2/phospholamban protein ratio (45% reduced;
      P=0.03). 45Ca sarcoplasmic endoplasmic reticular calcium ATPaseuptake assay
      showed reduced uptake velocity in HCM regardless of genotype (P=0.01). The
      cardiac ryanodine receptor was not altered in transcript, protein, or
      phosphorylated (pS2808, pS2814) protein abundance, and [3H]ryanodine binding was
      not different in HCM, consistent with no major modification of the ryanodine
      receptor. CONCLUSIONS: Human HCM demonstrates calcium mishandling through both
      genotype-specific and common pathways. Posttranslational activation of the CaMKII
      pathway is specific to sarcomere mutation-positive HCM, whereas sarcoplasmic
      endoplasmic reticular calcium ATPase 2 abundance and sarcoplasmic reticulum Ca
      uptake are depressed in both sarcomere mutation-positive and -negative HCM.

PMID- 27688317
TI  - Draft Genome Sequence of Bacillus litoralis C44, Isolated from Chinese Scholar
      Tree (Sophora japonica) Forest Soil.
AB  - Bacillus litoralis C44 can hydrolyze rutin to produce isoquercetin by the enzyme
      alpha-l-rhamnosidase. We report here the genome sequence and annotation result of
      strain C44. The genomic information will serve as references to the physiology,
      genetics, and evolution of this species and further genetic engineering research
      in this species. 

PMID- 27688316
TI  - Complete Genome Sequence of Gordonia terrae 3612.
AB  - Here, we report the complete genome sequence of Gordonia terrae 3612, also known
      by the strain designations ATCC 25594, NRRL B-16283, and NBRC 100016. The genome
      sequence reveals it to be free of prophage and clustered regularly interspaced
      short palindromic repeats (CRISPRs), and it is an effective host for the
      isolation and characterization of Gordonia bacteriophages. 

PMID- 27688318
TI  - Complete Genome Sequences of Campylobacter jejuni Strains OD267 and WP2202
      Isolated from Retail Chicken Livers and Gizzards Reveal the Presence of Novel 116
      Kilobase and 119-Kilobase Megaplasmids with Type VI Secretion Systems.
AB  - Genome sequences of Campylobacter jejuni strains OD267 and WP2202, isolated from
      chicken livers and gizzards, showed the presence of novel 116-kb and 119-kb
      megaplasmids, respectively. The two megaplasmids carry a type VI secretion system
      and tetracycline resistance genes. These are the largest sequenced Campylobacter
      plasmids to date. 

PMID- 27688319
TI  - Draft Genome Sequences of the Probiotic Enterococcus faecalis Symbioflor 1 Clones
      DSM16430 and DSM16434.
AB  - The probiotic Symbioflor 1 is a historical concoction of 10 isolates of
      Enterococcus faecalis Pulsed-field gel electrophoresis revealed two groups: one
      comprising eight identical clones (DSM16430, DSM16432, DSM16433, DSM16435 to
      DSM16439) and a further two isolates (DSM16431, DSM16434) with marginally
      different profiles. Here, we report a comparative analysis of the draft genome
      sequences of representative isolates. 

PMID- 27688321
TI  - Complete Genome Sequences of Two Dengue Virus Serotype 1 Genotype V Strains from
      Different Lineages.
AB  - Previous phylogenetic studies involving dengue virus serotype 1 (DENV1) have
      shown several lineages of genotype V circulating worldwide. After sequencing the
      complete genome of strains from Sao Jose do Rio Preto, Sao Paulo, Brazil, we
      identified a list of 50 different amino acids that differ between the two
      lineages, announced here. 

PMID- 27688320
TI  - Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Orion Strain
      CRJJGF_00093 (Phylum Gammaproteobacteria).
AB  - Here, we report a 4.70-Mbp draft genome sequence of Salmonella enterica subsp.
      enterica serovar Orion strain CRJJGF_00093, isolated from a dog in 2005. 

PMID- 27688322
TI  - Complete Genome Sequence of Geobacillus thermoglucosidasius NCIMB 11955, the
      Progenitor of a Bioethanol Production Strain.
AB  - The industrially important thermophile Geobacillus thermoglucosidasius has the
      potential to produce chemicals and fuels from biomass-derived sugar feedstocks.
      Here, we present the genome sequence of strain NCIMB 11955, the progenitor of an
      ethanologenic industrial strain, revealing 11 single-nucleotide polymorphisms and
      2 indels compared to strain DSM 2542 and two novel plasmids. 

PMID- 27688323
TI  - Genome Sequence of Klebsiella quasipneumoniae subsp. similipneumoniae MB373, an
      Effective Bioremediator.
AB  - Klebsiella quasipneumoniae subsp. similipneumoniae MB373 was isolated from
      effluent of the Hattar Industrial Estate, Haripur, Pakistan. K. quasipneumoniae
      subsp. similipneumoniae has few cultivated/characterized members so far. Whole
      genome sequencing revealed its potential for metal and toxin resistance, which
      further elucidated various enzymatic processes for the degradation of
      xenobiotics, illuminating its bioremediation applications. 

PMID- 27688324
TI  - Draft Genome Sequences of Four Species of Chlamydomonas Containing
      Phosphatidylcholine.
AB  - Phosphatidylcholine (PC) is one of the essential phospholipids for most
      eukaryotes. Although the model green alga Chlamydomonas reinhardtii lacks PC,
      four species containing PC were found in the genus Chlamydomonas Here, we report
      the draft genome sequences of the four species of Chlamydomonas containing PC. 

PMID- 27688325
TI  - Draft Genome Sequence of the Deep-Subsurface Actinobacterium Tessaracoccus
      lapidicaptus IPBSL-7T.
AB  - The type strain of Tessaracoccus lapidicaptus was isolated from the deep
      subsurface of the Iberian Pyrite Belt (southwest Spain). Here, we report its
      draft genome, consisting of 27 contigs with a ~3.1-Mb genome size. The annotation
      revealed 2,905 coding DNA sequences, 45 tRNA genes, and three rRNA genes. 

PMID- 27688326
TI  - Genome Sequences of 15 Gardnerella vaginalis Strains Isolated from the Vaginas of
      Women with and without Bacterial Vaginosis.
AB  - Gardnerella vaginalis is a predominant species in bacterial vaginosis, a
      dysbiosis of the vagina that is associated with adverse health outcomes,
      including preterm birth. Here, we present the draft genome sequences of 15
      Gardnerella vaginalis strains (now available through BEI Resources) isolated from
      women with and without bacterial vaginosis. 

PMID- 27688327
TI  - Genome Sequences of 12 Bacterial Isolates Obtained from the Urine of Pregnant
      Women.
AB  - The presence of bacteria in urine can pose significant risks during pregnancy.
      However, there are few reference genome strains for many common urinary bacteria.
      We isolated 12 urinary strains of Streptococcus, Staphylococcus, Citrobacter,
      Gardnerella, and Lactobacillus These strains and their genomes are now available
      to the research community. 

PMID- 27688328
TI  - Genome Sequences of 11 Human Vaginal Actinobacteria Strains.
AB  - The composition of the vaginal microbiota is an important health determinant.
      Several members of the phylum Actinobacteria have been implicated in bacterial
      vaginosis, a condition associated with many negative health outcomes. Here, we
      present 11 strains of vaginal Actinobacteria (now available through BEI
      Resources) along with draft genome sequences. 

PMID- 27688329
TI  - Genome Sequences of 14 Firmicutes Strains Isolated from the Human Vagina.
AB  - Research on vaginal infections is currently limited by a lack of available fully
      sequenced bacterial reference strains. Here, we present strains (now available
      through BEI Resources) and genome sequences for a set of 14 vaginal isolates from
      the phylum Firmicutes These genome sequences provide a valuable resource for
      future research in understanding the role of Gram-positive bacteria in vaginal
      health and disease. 

PMID- 27688330
TI  - Genome Sequences of Nine Gram-Negative Vaginal Bacterial Isolates.
AB  - The vagina is home to a wide variety of bacteria that have great potential to
      impact human health. Here, we announce reference strains (now available through
      BEI Resources) and draft genome sequences for 9 Gram-negative vaginal isolates
      from the taxa Citrobacter, Klebsiella, Fusobacterium, Proteus, and Prevotella. 

PMID- 27688331
TI  - A New Catalog of Microbiological Tools for Women's Infectious Disease Research.
AB  - Genitourinary infections pose serious health risks. But, little is known about
      how genitourinary bacteria attach, maintain colonization, compete for resources,
      and cause pathology. In this issue, we introduce a new set of 62 genitourinary
      reference strains of bacteria and their genomes to spur experimental research on
      infectious diseases that impact women. 

PMID- 27688333
TI  - Complete Genome Sequence of a Myoviridae Bacteriophage Infecting Salmonella
      enterica Serovar Typhimurium.
AB  - The bacteriophage 118970_sal3 was isolated from water buffalo feces in southern
      Italy, exhibiting lytic activity against Salmonella enterica serovar Typhimurium.
      This bacteriophage belongs to the Myoviridae family and has a 39,464-bp double
      stranded DNA (ds-DNA) genome containing 53 coding sequences (CDSs). 

PMID- 27688332
TI  - Genome Sequences of Newly Isolated Mycobacteriophages Forming Cluster S.
AB  - We describe the genomes of two mycobacteriophages, MosMoris and Gattaca, newly
      isolated on Mycobacterium smegmatis The two phages are very similar to each
      other, differing in 61 single nucleotide polymorphisms and six small
      insertion/deletions. Both have extensive nucleotide sequence similarity to
      mycobacteriophage Marvin and together form cluster S. 

PMID- 27688334
TI  - Complete Genome Sequence of a Lytic Siphoviridae Bacteriophage Infecting Several
      Serovars of Salmonella enterica.
AB  - The bacteriophage 100268_sal2 was isolated from water buffalo feces in southern
      Italy, exhibiting lytic activity against several subspecies of Salmonella
      enterica This bacteriophage belongs to the Siphoviridae family and has a 125,114
      bp double-stranded DNA (ds-DNA) genome containing 188 coding sequences (CDSs). 

PMID- 27688335
TI  - Genome Sequence of Bacillus cereus Group Phage SalinJah.
AB  - The double-stranded DNA (dsDNA) Myoviridae Bacillus cereus group bacteriophage
      SalinJah was isolated from soil collected in Gyeonggi-do, South Korea. SalinJah,
      a cluster C phage with a broad host range, suggests the need to create a new
      subcluster with SalinJah and Helga as founding members. 

PMID- 27688336
TI  - Draft Genome Sequence of the Environmentally Isolated Acinetobacter pittii Strain
      IPK_TSA6.1.
AB  - Acinetobacter pittii is an opportunistic pathogen frequently isolated from
      Acinetobacter infections other than those from Acinetobacter baumannii Multidrug
      resistance in A. pittii, including resistance to carbapenems, has been
      increasingly reported worldwide. Here, we report the 4.14-Mbp draft genome
      sequence of A. pittii IPK_TSA6.1 that was isolated from a nonhospital setting. 

PMID- 27688337
TI  - Complete Genome Sequence of Enterococcus faecalis Strain W11 Isolated from an
      Algal Food Product.
AB  - Here, we report the complete genome sequence of Enterococcus faecalis strain W11
      isolated from an algal food product in Japan. This study should facilitate the
      identification of a novel mechanism of glycerol metabolic control in lactic acid
      bacteria. 

PMID- 27688338
TI  - Complete Genome Sequence of Staphylococcus carnosus LTH 3730.
AB  - Specific strains of the apathogenic coagulase-negative species Staphylococcus
      carnosus are frequently used as meat starter cultures, as they contribute to
      color formation and the production of aroma compounds. Here, we report the
      complete genome sequence of S. carnosus LTH 3730, a strain isolated from a
      fermented fish product. 

PMID- 27688340
TI  - Draft Genome Sequence of Bacillus cereus LCR12, a Plant Growth-Promoting
      Rhizobacterium Isolated from a Heavy Metal-Contaminated Environment.
AB  - Bacillus cereus LCR12 is a plant growth-promoting rhizobacterium, isolated from a
      heavy metal-contaminated environment. The 6.01-Mb annotated genome sequence
      provides the genetic basis for revealing its potential application to remediate
      contaminated soils in association with plants. 

PMID- 27688339
TI  - Draft Genome Sequences of Four Hospital-Associated Pseudomonas putida Isolates.
AB  - We present here the draft genome sequences of four Pseudomonas putida isolates
      belonging to a single clone suspected for nosocomial transmission between
      patients and a bronchoscope in a tertiary hospital. The four genome sequences
      belong to a single lineage but contain differences in their mobile genetic
      elements. 

PMID- 27688341
TI  - Application of Long Sequence Reads To Improve Genomes for Clostridium
      thermocellum AD2, Clostridium thermocellum LQRI, and Pelosinus fermentans R7.
AB  - We and others have shown the utility of long sequence reads to improve genome
      assembly quality. In this study, we generated PacBio DNA sequence data to improve
      the assemblies of draft genomes for Clostridium thermocellum AD2, Clostridium
      thermocellum LQRI, and Pelosinus fermentans R7. 

PMID- 27688342
TI  - Complete Genome Sequence of the Endophytic Biocontrol Strain Bacillus velezensis
      CC09.
AB  - Bacillus velezensis is a heterotypic synonym of B. methylotrophicus, B.
      amyloliquefaciens subsp. plantarum, and Bacillus oryzicola, and has been used to
      control plant fungal diseases. In order to fully understand the genetic basis of
      antimicrobial capacities, we did a complete genome sequencing of the endophytic
      B. velezensis strain CC09. Genes tightly associated with biocontrol ability,
      including nonribosomal peptide synthetases, polyketide synthetases, iron
      acquisition, colonization, and volatile organic compound synthesis were
      identified in the genome. 

PMID- 27688343
TI  - First Complete Genome Sequence of Bean common mosaic necrosis virus from East
      Timor.
AB  - We present here the first complete Bean common mosaic necrosis virus (BCMNV)
      genomic sequence isolated from virus-infected common bean (Phaseolus vulgaris) in
      East Timor, and compare it with six complete BMCNV genomes from the Netherlands,
      and one each from the United States, Tanzania, and an unspecified country. It
      most resembled the Netherlands strain NL-8 genome. 

PMID- 27688344
TI  - Complete Genome Sequence of Mycobacterium ulcerans subsp. shinshuense.
AB  - Mycobacterium ulcerans subsp. shinshuense produces mycolactone and causes Buruli
      ulcer. Here, we report the complete sequence of its genome, which comprises a 5.9
      Mb chromosome and a 166-kb plasmid (pShT-P). The sequence will represent the
      essential data for future phylogenetic and comparative genome studies of
      mycolactone-producing mycobacteria. 

PMID- 27688345
TI  - Back to the Future of Dental Education: "Lock up your libraries if you like, but
      there is no gate, no lock, no bolt that you can set upon the freedom of my
      mind"?Virginia Woolf, A Room of One's Own, 1929.
AB  - Our students are like beacons, a bright light on the horizon, but with some way
      to go. Our educational methods that bring them safely into harbour have seen the
      test of time, but do we allow them enough freedom and creativity to sail their
      boats in the climate change of the digital era? Our students are chosen because
      they are smart and capable and we hope will bring credit to our institutions, but
      do we maximize their potential educationally? We need to go back to the future to
      begin to consider this. 

PMID- 27688346
TI  - The Use of Lasers in Disinfection and Cleanliness of Root Canals: a Review.
AB  - The outcome of root canal treatment is based on efficient disinfection of the
      root canal system and prevention of reinfection. Current chemomechanical cleaning
      methods do not always achieve these goals, and insufficient root canal
      disinfection is the main reason for endodontic failure. Due to high energy
      content and specific characteristics of laser light, laser treatment has been
      proposed for cleaning and disinfecting the root canal system. This paper reviews
      the literature covering the effect of Er:YAG, Er,Cr:YSGG, Nd:YAG and diode laser
      on the root canal wall in the removal of smear layer and against intracanal
      bacteria. Recently, the use of laser energy to induce cavitation and acoustic
      streaming of intracanal irrigants has been investigated. Based on recent
      literature, it can be concluded that lasers have bactericidal effects. However,
      they still cannot replace sodium hypochlorite and should be considered as an
      adjunct to the current chemical root canal disinfection protocols. Certain lasers
      can help in removing the smear layer and debris and can modify the morphology of
      the root canal wall. Unfortunately, there have not been enough randomized
      clinical studies evaluating endodontic treatment outcome following the use of
      laser. 

PMID- 27688348
TI  - Assessment of implant stability following sinus lift procedures with different
      grafting materials.
AB  - OBJECTIVE: The objective of this research was to evaluate implant stability
      following sinus lift with two grafting materials, and to compare it with the
      results obtained for the implants placed in a pristine posterior maxilla.
      MATERIALS AND METHODS: The study included 44 healthy patients with an existing
      indication for sinus lift procedure (test group). 46 implants were placed
      following sinus lift with a pure-phase beta-tricalcium phosphate, while 39
      implants were placed following augmentation with 60% hydroxyapatite with 40% beta
      tricalcium phosphate material. The control group consisted of 48 healthy patients
      who were treated with 85 implants but without bone augmentation in posterior
      maxilla. Astra Tech OsseoSpeed implants were placed in all subjects. Resonance
      frequency analysis was used in both groups for determining implant stability 4
      months after insertion. A mean implant stability quotient (ISQ) was calculated on
      the basis of 3 measurements. RESULTS: No statistical difference was observed in
      ISQ values of implants placed with and without augmentation procedure (p=0,789).
      Statistically significant difference was not found when ISQ values of implants
      placed following particular grafting material were compared with ISQ values of
      corresponding implants in a pristine bone (p=0.697 and p=0.402). CONCLUSIONS:
      This study demonstrated that the implant stability is comparable among implants
      placed in the posterior maxilla regardless of sinus lift and grafting procedure.
      Implants placed in the grafted posterior maxilla can be predictably loaded as the
      implants placed in a non-grafted, pristine maxilla.

PMID- 27688347
TI  - Effect of Endodontic Irrigating Solutions on the Micro Push-out Bond Strength of
      a Fibre Glass Dowel.
AB  - PURPOSE: To evaluate the effect of different endodontic irrigating solutions on
      the micro push-out bond strength of a fiber glass dowel. MATERIAL AND METHODS:
      Seventy 16-mm long root segments of bovine incisors were prepared and randomly
      assigned to 7 groups (n=10) according to the type of irrigating solution used
      prior to the cementation of the intra-radicular fiber glass dowels: G1: 5.25%
      NaOCl + 17% EDTA; G2: 5.25% NaOCl; G3: 17% EDTA; G4: 2% chlorhexidine gel; G5:
      70% alcohol; G6: 11.5% polyacrylic acid; and G7: saline (control). After
      treatment of intracanal dentin, the glass fibre dowels were cemented with self
      adhesive resin cement (RelyX Unicem). Six slices with the thickness of 1.00 +/-
      0.05 mm were obtained from each tooth at the coronal, middle and apical root
      thirds (2 slices per third) using a low-speed saw. Micro push-out tests were
      performed at a crosshead speed of 0.5mm/min and the data (MPa) were analyzed
      statistically by ANOVA and Tukey's and Dunnett's tests. RESULTS: There were
      statistically significant differences (p<0.0001) among the irrigating solutions,
      but no significant difference (p=0.0591) was found among the root thirds. G5
      presented the highest bond strength mean of all groups (p<0.0001). The use of 70%
      alcohol increased the adhesion values by 53% compared to the group control.
      CONCLUSION: The use of 70% alcohol increased the bond strength of the fiber glass
      dowel to the dentin walls. However, the push-out bond strength between the dowel
      and the root dentin was not affected by the root third (coronal, middle and
      apical).

PMID- 27688349
TI  - Influence of Gender on the Patient's Assessment of Restorations on the Upper
      Anterior Teeth.
AB  - OBJECTIVE: The aim of this study was to assess the level of patients'
      satisfaction with appearance of maxillary anterior teeth restorations and to
      determine if there is a significant difference in patients' assessment of
      restoration appearance with regard to gender. MATERIALS AND METHODS: Two hundred
      subjects evaluated the colour, anatomical shape and surface texture of maxillary
      anterior teeth restorations (composite fillings, acrylic faceted metal crowns,
      porcelain-fused-to-metal crowns and all-ceramic crowns) in comparison with
      adjacent natural teeth. The data were expressed in patients' average assessment
      scores for colour, anatomical shape and surface texture as well as overall
      patients' average assessment scores for every type of restoration and overall
      patients' average assessment scores for colour, anatomical shape and surface
      texture of all the restorations in general. Patients also assessed the general
      impression of their maxillary anterior teeth restorations and rated it as
      satisfactory or unsatisfactory. RESULTS: There was a statistically significant
      gender difference in patient assessment of colour and surface texture for
      composite fillings and the overall patient average assessment score for colour of
      all assessments (p <0.05). Women were more dissatisfied with the general
      impression of their restorations on the upper teeth than men (p >0.05). Only
      overall patients' average assessment score for composite restorations almost
      reached the level of significance (p = 0.069) on patients' general impression.
      CONCLUSION: Colour of the restorations and the composite material are significant
      factors which affect dental appearance of maxillary anterior teeth in patients.

PMID- 27688350
TI  - The importance of a proper selection area to be biopsied in nodular leukoplakia:
      a case report.
AB  - Nodular leukoplakia is a non-homogeneous type of oral leukoplakia presenting a
      white surface with verrucous, nodular, ulcerated or erythematous features with a
      greater risk of malignant transformation when compared to the homogeneous type.
      Common sites of involvement include lip commissures, buccal mucosa and soft
      palate. It is often associated with epithelial dysplasia or carcinoma and
      requires detailed microscopic assessment and regular follow-up. The importance of
      a proper selection of the area to be biopsied and the close teamwork between a
      dentist and oral pathologist is the basis of providing an accurate final
      diagnosis. 

PMID- 27688352
TI  - FORENSIC SCIENCE:: 20 YEARS OF FORENSIC DENTISTRY AT THE UNIVERSITY OF ZAGREB,
      1994 - 2014.
AB  - Data from available literature point to an early beginning of Forensic Dentistry
      in Croatia relating to a post-mortem examination of a female patient after a
      dental procedure in the 1930s. Later on, there were several mass casualties due
      to collisions and airplane crashes and a railway accident at the Zagreb Main
      Railway Station wherein the identity of the victims was established based on
      dental features. Foreign experts in forensics helped identify those victims,
      particularly forensic dentists because this specialty was almost unknown in our
      region at the time. During the twenty-year period of the development of Forensic
      Dentistry at the University of Zagreb, the School of Dental Medicine, the city of
      Zagreb and Croatia have become internationally recognised on the forensic map of
      the world. 

PMID- 27688351
TI  - Atypical Presentation of an Upper Lip Pleomorphic Adenoma: Case Report.
AB  - The pleomorphic adenoma (PA) or mixed tumor is the most common neoplasm of the
      salivary glands, usually presenting with a non-specific clinical manifestation
      and a diverse histopathological pattern. The region of the lips is the second
      most common site for minor gland neoplasms. The aim of this paper is to report
      the case of a 39 year old caucasian woman presenting with a swelling on the right
      side of the upper lip combined with a history of trauma in the region of the
      upper right central incisor, eight years ago. The swelling was attributed to the
      periapical lesion of the upper right central incisor that was observed on the
      orthopantomography. Intraoperatively the surgeon came upon a nodule of firm
      consistency in the mucolabial fold. The histopathologic diagnosis of this lesion
      was benign mixed tumor of salivary gland. This report discusses the deviation in
      frequency of mixed salivary gland tumor between upper and lower lip, the clinical
      differential diagnosis, the histopathological pattern and the appropriate
      treatment. 

PMID- 27688353
TI  - Three-Dimensional Human Cell Cultures for Cytotoxicity Testing of Dental Filling
      Materials.
AB  - OBJECTIVES: So far, bovine immortalized pulp cells have been used as three
      dimensional cultures for cytotoxicity testing of filling materials in the dentin
      barrier test (DBT). In this study, the use of human pulp-derived cells was
      evaluated, which would better simulate the clinical situation, and a composite
      material with a new resin base was tested. MATERIALS AND METHODS: SV40
      transfected human pulp cells (tHPC) were cultured in hydrogels (fibrin, peptide,
      collagen) and mechanical properties and cell viability (MTT or WST-1) were
      determined. For cell cultures in collagen, a four week - proliferation assay was
      performed (WST-1). After 14 days of three-dimensional culture in collagen, tHPC
      were introduced into the DBT with 200 um dentin disks. After a 24-hour incubation
      under perfusion (0.3 ml/h), the following materials were applied according to the
      manufacturers' instructions (1) President (Coltene): negative (non-toxic)
      control, (2) CaGPG14 (ISO 7405): positive (toxic) control, (3) Tetric EvoCeram
      (Ivoclar Vivadent) with Clearfil SEBond (Kuraray, reference material), (4)
      N'Durance (Sepodont, test material), (5) N'Durance with Clearfil SEBond. Cell
      viability was determined after 24-hour incubation (WST-1). The percentage of
      relative viability was calculated (negative control=100%) and statistically
      analyzed (Kruskal-Wallis-test, p<0.05). RESULTS: Fibrin and peptide gels had
      insufficient mechanical properties for the DBT Collagen and appeared suitable for
      three-dimensional cell culture of tHPC for up to 21 days. The cultures could be
      transferred to the DBT device and results for controls were similar to previous
      tests with bovine cells. The DBT using tHPC in the collagen showed no
      statistically significant difference between the test material with and without
      the adhesive and the reference resin composite. CONCLUSIONS: tHPC in collagen can
      replace bovine cells in the DBT. The tested filling material is not likely to
      cause pulp damage, if the pulp is covered by an intact dentin layer.

PMID- 27688354
TI  - CATASTROPHIZING IN PATIENTS WITH BURNING MOUTH SYNDROME.
AB  - BACKGROUND: Burning mouth syndrome (BMS) is an idiopathic painful condition which
      manifests with burning sensations in the oral cavity in patients with clinically
      normal oral mucosa and without any local and/or systemic causative factor.
      Catastrophizing is defined as an exaggerated negative orientation toward pain
      stimuli and pain experience. The aim of this study was to examine the association
      between catastrophizing and clinical parameters of BMS, and to examine the
      association between catastrophizing and the quality of life in patients with BMS.
      MATERIALS AND METHODS: Anonymous questionnaire consisting of 3 parts (demographic
      and clinical data with 100 mm visual analogue scale (VAS), Croatian version of
      the Oral Health Impact Profile (OHIP-14) scale and Croatian version of the Pain
      Catastrophizing scale (PC), was distributed to 30 patients diagnosed with BMS.
      RESULTS: A higher level of catastrophizing was clinically significant in 30% of
      the patients. Total catastrophizing score and all three subcomponents of
      catastrophizing significantly correlated with the intensity of symptoms, but did
      not correlate with the duration of symptoms. Gender and previous treatment did
      not affect the catastrophizing. CONCLUSION: Obtaining the information about
      catastrophizing could help a clinician to identify patients with negative
      behavioural patterns. Additional psychological intervention in these individuals
      could reduce/eliminate negative cognitive factors and improve coping with chronic
      painful condition such as BMS.

PMID- 27688355
TI  - Detection of Sulphate-Reducing Bacteria and Others Cultivable Facultative
      Bacteria in Dental Tissues.
AB  - AIM: To detect for the presence of sulphate-reducing bacteria (SRB) and evaluate
      the possible association between SRB and cultivable facultative bacterial of oral
      sites with different periodontal conditions. METHODS: The study was carried out
      on 9 samples from different oral sites in 8 patients (two samples were collected
      from the same patient). Material was collected using modified Postgate E culture
      medium, indicated for the growth and isolation of SRB. In addition, a reducing
      solution for anaerobic bacteria was used as a transport solution for facultative
      bacteria and identified by polymerase chain reaction amplification (PCR) and
      sequencing of the 16S rRNA gene. RESULTS: SRB was found in 3 patient samples: the
      first in a root fragment, the second in a root fragment and a healthy tooth with
      vertical bone loss and a mobility degree of 3; and the third in a healthy tooth
      extracted for orthodontic treatment. In the final patient, the cultivable
      facultative species Lactobacillus casei was identified. Other facultative
      bacterial species were identified in patient 5 (Kurthia Gibsonii) and patient 7
      (Pseudomonas aeruginosa). CONCLUSIONS: The detection of SRB in different dental
      tissues with distinct periodontal features demonstrated that new studies need to
      be developed in order to determine the true role of SRB in the oral microbiota.
      In addition, it was possible to verify the presence of Lactobacillus casei
      together with SRB in one sample.

PMID- 27688356
TI  - A Comparative in Vitro Study of Apical Microleakage with Five Obturation
      Techniques: Lateral Condensation, Soft-Core(r), Obtura II(r), Guttaflow(r) and
      Resilon(r).
AB  - AIM: A comparison was made between the root canal lateral condensation technique
      and other condensation techniques in which physical (temperature: Soft-Core(r),
      Obtura II(r)) or chemical changes (condensation: Guttaflow(r), Resilon(r)) may
      affect the dimensional stability of obturation and thus favor apical
      microleakage. MATERIALS AND METHODS: A total of 212 single-root teeth removed for
      orthodontic or periodontal reasons were randomized to 5 groups of 40 teeth each.
      Six samples were used as positive controls, and another 6 as negative controls.
      The teeth were worked with the Hero 642 system, and each group was obturated
      using a different technique: lateral condensation, Obtura II(r), Soft-Core(r),
      Guttaflow(r) or Resilon(r). The samples were immersed in black ink, and after 72
      hours the teeth were transparentized using the technique described by Robertson.
      Filtration of the ink was measured under the stereoscopic microscope. Analysis of
      variance and post-hoc testing were used for the statistical analysis. RESULTS:
      The Soft-Core(r) obturated group showed significantly greater microleakage than
      the other groups, with no differences among the rest of the groups. CONCLUSIONS:
      Under the conditions of this study, the teeth obturated with the Soft-Core(r)
      technique showed greater apical microleakage than the other systems.

PMID- 27688357
TI  - Apical Sealing Ability of a Novel Material: Analysis by Fluid Filtration
      Technique.
AB  - AIM: The aim of this study is to evaluate the sealing ability of Biodentine(TM),
      which is new calcium-silicate based dental cement and has endodontic indications
      similar to those of MTA. METHODS: The study sample consists of 21extracted human
      mandibular anterior teeth. The teeth were submitted to root-end preparation and
      instrumented up to file #40 by step back technique and randomly divided into 3
      study groups (n=7): White MTA Angelus(TM) (Angelus, Angelus Odontologica,
      Londrina, PR, Brazil), Biodentine(TM) (Septodont, SeptodontSpecialites, Saint
      MaurdesFosses, France) and the controls. The length of dye penetration between
      the filling material and tooth structure was measured in millimetres, using a
      calibrated stereo microscope (Leica MZ75, Germany) at 20* magnification under the
      same conditions. One-way Analysis of Variance (ANOVA) was used to indicate
      differences between the experimental groups and the controls. In addition, Tukey
      Multiple Comparisons Test was used to indicate differences within each group.
      RESULTS: The results showed that none of the groups were completely sealed. The
      mean and standard deviation for dye penetration in Biodentine(TM) group was
      0.63+/-0.20 and in MTA Angelus(TM) group, it was 0.26+/-0.25. Regarding the
      comparisons between each group, significant differences were not observed
      (P=0.0193). The comparison between materials only found a significant difference
      only between MTA Angelus(TM) and Biodentine(TM) (P<0.05). CONCLUSIONS: This study
      evaluated the possibility of Biodentine(TM)'s sealing ability and marginal
      adaptation, since no studies are available on Biodentine. However, further in
      vitro and in vivo investigations should be conducted to determine the suitability
      of Biodentine(TM) for clinical application.

PMID- 27688358
TI  - Attitude towards Oral Health at Various Colleges of the University of Zagreb: A
      Pilot Study.
AB  - PURPOSE: The aim of this study was to compare the oral status of three various
      groups of students: students of the School of Dental Medicine, students of
      technical sciences and students of humanities. MATERIAL AND METHODS: Research
      included 58 students of the University of Zagreb. They answered 3 questions: how
      often they brush their teeth, how often they visit their dentist and how
      important dental health is to them. After a standard dental check-up we
      calculated the DMFT index. They were given an indicator for plaque Mira-2-Ton(r)
      (Hager Werken, Duisburg, Germany) and we calculated the plaque index. For
      statistical analysis the ANOVA test was used. RESULTS: Students of the School of
      Dental Medicine had a lower plaque index than other students and this was
      statistically significant (p=0.0018; f=7.14). They also had a lower DMFT index,
      but it was not statistically significant (p=0.1004; f=2.4). 83% of students said
      that they brushed their teeth 2-3 times a day. Only 17% of all students brush
      their teeth more than 3 times a day and they are all students of the School of
      Dental Medicine (21% of them). Perception of oral health is on a high level, but
      perception of oral disease is not. The social approval of the answer was also an
      important factor. CONCLUSION: Students of the School of Dental Medicine are an
      illustrative example of improving our habits due to education.

PMID- 27688359
TI  - Dental Identification Through Endodontic Radiographic Records: a Case Report.
AB  - OBJECTIVE OF WORK: The present study aims to report a case of successful human
      identification based on the comparison of ante-mortem and post-mortem records of
      endodontic treatment. Based on these, the legal value of storing and updating
      clinical records is highlighted throughout the text. CASE REPORT: An unknown body
      was recovered from a traffic accident site. Forensic examination was conducted in
      order to establish the identity of the victim. Based on the absence of ante
      mortem fingerprint registration in the national database, the search for AM data
      was performed using periapical radiographic records from private dental clinics.
      A positive dental identification was achieved analyzing evidence of endodontic
      treatment. CONCLUSION: Dental radiographs play a valuable role as legal tools
      supporting the criminal demands on the daily forensic practice. Specifically in
      endodontics, periapical radiographs are essential for a proper treatment. In
      forensics, these radiographs represent a solid source of ante-mortem data for
      human identifications.

PMID- 27688360
TI  - Egg Freezing in Childhood and Young Adult Cancer Survivors.
AB  - Fertility preservation in prepubertal and young adolescent girls scheduled for
      chemotherapy is a demanding situation. Despite the recent impressive improvements
      of ovarian cortex cryopreservation, significant limitations persist. The
      technique remains experimental, it exposes the girl to the risks of surgery and
      to an iatrogenic insult to the ovarian reserve, and there is no guarantee of use
      because not all girls will undergo re-implantation. Moreover, it is impossible to
      respect all the requested conditions for a valid informed consent. The girl is
      minor, the time for decision is very short, and the prospect of not surviving
      clouds both the girl and her relatives. An alternative but neglected option is
      oocyte cryopreservation after the end of cancer treatments, when the girl reaches
      adulthood. This possibility can overcome some of the limitations of ovarian
      cortex freezing and may be considered for girls scheduled for a chemotherapy at
      low or medium risk of ovarian reserve impairment. In this case report, we
      describe the case of a young female patient with cancer who survived 2
      chemotherapies for 2 distinct cancers and who was diagnosed with reduced ovarian
      reserve. The patient underwent 3 cycles of ovarian hyperstimulation and
      ultimately stored 19 oocytes. The success obtained in this girl suggests
      consideration of egg freezing as an alternative fertility-preservation procedure
      in prepubertal and young adolescent girls scheduled for chemotherapy. However,
      cryopreservation of ovarian tissue remains the only option for those scheduled
      for chemotherapies at high risk of ovarian reserve impairment.

PMID- 27688361
TI  - Safety of Oral Propranolol for the Treatment of Infantile Hemangioma: A
      Systematic Review.
AB  - BACKGROUND AND OBJECTIVES: Given the widespread use of propranolol in infantile
      hemangioma (IH) it was considered essential to perform a systematic review of its
      safety. The objectives of this review were to evaluate the safety profile of oral
      propranolol in the treatment of IH. METHODS: We searched Embase and Medline
      databases (2007-July 2014) and unpublished data from the manufacturer of
      Hemangiol/Hemangeol (marketed pediatric formulation of oral propranolol; Pierre
      Fabre Dermatologie, Lavaur, France). Selected studies included >=10 patients
      treated with oral propranolol for IH and that either reported >=1 adverse event
      or effect (AE) or planned to capture AEs. Data capture was standardized and
      extracted study design, demographic characteristics, IH characteristics,
      intervention, and safety outcomes. AEs were assigned a system organ class and
      preferred term. RESULTS: A total of 83 of 398 identified literature records met
      the inclusion criteria, covering 3766 propranolol-treated patients. The
      manufacturer's data for 3 pooled clinical trials (435 propranolol-treated
      patients) and 1 Compassionate Use Program (1661 patients) were included. AE data
      were reported for 1945 of 5862 propranolol-treated patients. The most frequently
      reported AEs included a range of sleep disturbances, peripheral coldness, and
      agitation. The most serious AEs (atrioventricular block, bradycardia,
      hypotension, bronchospasm/bronchial hyperreactivity, and hypoglycemia-related
      seizures) were managed by decreasing doses or temporary/permanent discontinuation
      of propranolol. Limitations included the variety of included study designs;
      monitoring, collection, and reporting of AE data; small sample sizes for some
      articles; and the wide scope of review. CONCLUSIONS: Oral propranolol is well
      tolerated if appropriate pretreatment assessments and within-treatment monitoring
      are performed to exclude patients with contraindications and to minimize serious
      side effects during treatment.

PMID- 27688363
TI  - Digitalization of "Acta Stomatologica Croatica" Journal (1966;1 - 1999;33).
AB  - Modern documents, scientific articles and books are primarily issued in
      electronic form and their availability depends on the publisher's, or the
      document owner's, business ethics. The primary purpose of publishing a scientific
      article is to communicate with the scientific and professional community;
      therefore, the published article has to be available worldwide. The question is:
      Who really needs scientific papers from the 1960's? In cases of brilliant and
      bold visionaries, new concepts and scientific discoveries often come before their
      time; hence they have to be "reinvented" decades later. Besides, the scientists
      of today can enter the spiritual spheres of their professional ancestors and give
      respect to their legacy.?We have processed more than 1 200 articles published by
      1999 and entered more than?6 000 names and surnames of authors. 

PMID- 27688364
TI  - Factors Affecting Oral Health-Related Quality of Life Among Elderly Croatian
      Patients.
AB  - OBJECTIVE OF WORK: Oral health-related quality of life (OHRQoL) as a
      multidimensional concept is affected by many factors. Therefore, the aim of this
      study was to determine which demographic and subjective factors are significantly
      affecting the OHRQoL among the elderly people wearing complete removable dental
      prostheses (CRDP). MATERIALS AND METHODS: This questionnaire-based study included
      301 participants, residents of elderly care homes (in Zagreb and Slavonski Brod,
      Croatia) wearing maxillary and/or mandibular CRDP. The questionnaire used in this
      study consisted of two sections; the first section included questions giving
      general information and in the second section the Croatian version of Oral Health
      Impact Profile (OHIP)-49 questionnaire with 49 items representing seven OHIP
      domains was used. RESULTS: Participants were aged between 60-99 years, with
      average age of 74 +/- 12.1 years. OHIP summary score was 26.5. The highest
      average OHIP mean values in the domain of functional limitation amounted to 6.7,
      physical pain 5.1, and physical disability 5.9. The participants' age, education,
      profession, residence place size, type of CRDP, and the time of denture wearing
      period all statistically significantly affected OHRQoL (p < 0.05). CONCLUSIONS:
      General and sociodemographic factors had a significant influence on the
      participant's subjective perception of oral health and OHRQoL. Younger
      participants, participants from rural places, those with lower levels of
      education, and shorter period of denture wearing demonstrated a higher impact on
      OHRQoL.

PMID- 27688362
TI  - Predicting Severe Pneumonia Outcomes in Children.
AB  - BACKGROUND: Substantial morbidity and excessive care variation are seen with
      pediatric pneumonia. Accurate risk-stratification tools to guide clinical
      decision-making are needed. METHODS: We developed risk models to predict severe
      pneumonia outcomes in children (<18 years) by using data from the Etiology of
      Pneumonia in the Community Study, a prospective study of community-acquired
      pneumonia hospitalizations conducted in 3 US cities from January 2010 to June
      2012. In-hospital outcomes were organized into an ordinal severity scale
      encompassing severe (mechanical ventilation, shock, or death), moderate
      (intensive care admission only), and mild (non-intensive care hospitalization)
      outcomes. Twenty predictors, including patient, laboratory, and radiographic
      characteristics at presentation, were evaluated in 3 models: a full model
      included all 20 predictors, a reduced model included 10 predictors based on
      expert consensus, and an electronic health record (EHR) model included 9
      predictors typically available as structured data within comprehensive EHRs.
      Ordinal regression was used for model development. Predictive accuracy was
      estimated by using discrimination (concordance index). RESULTS: Among the 2319
      included children, 21% had a moderate or severe outcome (14% moderate, 7%
      severe). Each of the models accurately identified risk for moderate or severe
      pneumonia (concordance index across models 0.78-0.81). Age, vital signs, chest
      indrawing, and radiologic infiltrate pattern were the strongest predictors of
      severity. The reduced and EHR models retained most of the strongest predictors
      and performed as well as the full model. CONCLUSIONS: We created 3 risk models
      that accurately estimate risk for severe pneumonia in children. Their use holds
      the potential to improve care and outcomes.

PMID- 27688365
TI  - Idiopathic Osteosclerosis of the Jaw in a Brazilian Population: a Retrospective
      Study.
AB  - OBJECTIVES: To report cases of idiopathic osteosclerosis (IO), to review the
      literature on the subject, and to discuss its main characteristics, diagnosis,
      differential diagnosis, and treatment. MATERIAL AND METHODS: Retrospective
      analysis of 354 panoramic radiographs, searching for IO, its size, shape,
      location, and noting patients' demographic information. Literature review used
      Medline and Lilacs databases and the terms idiopathic osteosclerosis OR bone
      sclerosis OR dense bone island AND jaws. RESULTS: IO was identified in 5.6% of
      the radiographs (n=20 patients, 22 foci). Patients were healthy, with an age
      ranging from 5 to 51 years (mean=29.8), with male-female ratio of 3:2. IOs were
      found mainly in the premolar/molar region, at root apices, between roots, away
      from the teeth, laterally to the tooth, and in edentulous areas. The distribution
      between right and left sides of the jaw was equal for the 22 foci, with only one
      case in the maxilla. IOs were localized, well-defined, radiopaque, mostly round
      or ovoid in shape, but sometimes irregular. In some cases, IOs were similar to
      condensing osteitis, but differential diagnosis also considered complex odontoma,
      focal cemento-osseous dysplasia, and residual roots. Twenty studies on the topic
      were reviewed. CONCLUSIONS: Incidence of IO in the Brazilian sample was 5.6%,
      with age ranging from 5 to 51 years (mean=29.8), and male-female ratio of 3:2.
      The radiopacities occurred in different locations, with significant prevalence in
      the mandible. The findings and the literature review corroborate the hypothesis
      that IO should be considered developmental variation of normal bone that does not
      require treatment.

PMID- 27688366
TI  - Use of Pre-Injection Diffusion of Local Anaesthetic as a Means of Reducing Needle
      Penetration Discomfort.
AB  - AIM: To determine if pre-injection diffusion of local anaesthetic solution
      influences the discomfort of needle penetration in the palate. METHODS: A placebo
      controlled, randomised, double-blind split-mouth investigation was conducted. 25
      healthy adult volunteers were recruited and each received two needle penetrations
      in a random order during one visit. The penetration sites were 1 cm from the
      gingival margin of the first maxillary premolars on each side of the mouth. 30
      gauge-13 mm needles which were attached to syringes that contained either 2%
      lidocaine with 0.125mg/ml epinephrine or physiological saline were used. For each
      penetration an operator encouraged a drop of solution to appear at the end of the
      needle and placed this drop with the bevel of the needle flat on the palate for
      20 seconds. The discomfort was noted on a 100 mm visual analogue scale with end
      points marked "No pain" and "Unbearable pain". RESULTS: There was no significant
      difference in penetration discomfort between solutions, (mean VAS = 26.80+/
      19.36mm for lidocaine and 26.20+/-18.39mm for saline) however the 2nd penetration
      was significantly more uncomfortable than the first (mean VAS = 31.00+/-19.84 mm
      and 22.00+/-16.65 mm respectively). CONCLUSION: Pre-injection diffusion of local
      anaesthetic solution did not influence the discomfort of needle penetration in
      the palate.

PMID- 27688367
TI  - A Survey of Removable Partial Denture (RPD) Retentive Elements in Relation to the
      Type of Edentulism and Abutment Teeth Found in Commercial Laboratories, Athens,
      Greece.
AB  - OBJECTIVE: The aim of this survey was to record removable partial denture (RPD)
      retentive elements and abutment teeth in partially edentulous patients,
      identified in commercial laboratories in Athens, Greece. MATERIAL AND METHODS:
      628 master casts with the corresponding cast metal frameworks used in the
      construction of RPDs were evaluated. Casts were photographed to identify the
      number and position of existing teeth, the partial edentulism class and the
      retentive elements. Prevalence tables and the x(2) test were used for the
      statistical analysis of the collected data (alpha=.05). RESULTS: There were 276
      maxillary (43.9%) and 352 (56.1%) mandibular casts. Maxillary edentulism entailed
      almost a total absence of right third molars in 96.7% and left third molars 96.0%
      of casts, with lower rates for the first and second molars. Edentulism in the
      posterior mandible presented a similar pattern. The most profound findings
      concerning retentive elements were: 91.9% of the retainers used were clasps and
      the remaining 8.1% were attachments. Of the clasps used, 48.9% were of the Roach
      Tau type, a finding more common in Kennedy Class I as compared to other Kennedy
      Classes (p<0.01). The circumferential clasps accounted for 19.3% of the total
      clasps used, and it was less frequently presented (8.8%) in Kennedy I Classes
      (p<0.01). CONCLUSIONS: Roach clasps were used in the majority of cases whereas
      RPI clasps and attachments were rarely used.

PMID- 27688368
TI  - A Fast Method for DEFB1 - 44C/G SNP Genotyping in Brazilian Patients with
      Periodontitis.
AB  - AIM: Defensins are cationic antimicrobial peptides expressed in epithelial cells.
      Such peptides exhibit antibacterial, antifungal and antiviral properties, and are
      a component of the innate immune response. It has been suggested that they have a
      protective role in the oral cavity. This study evaluated the DEFB1 polymorphism
      in diabetic patients with or without periodontitis in comparison to healthy
      controls. MATERIAL AND METHODS: We used Hairpin-Shaped Primer (HP) assay to study
      the distribution of the -44 C/G SNP (rs1800972) in 119 human DNAs obtained from
      diabetic patients and healthy control patients. RESULTS: The results indicate
      that there are no differences in distribution between groups and that in diabetic
      periodontitis patients the homozygous mutant could be found more frequently.
      CONCLUSION: Further studies are necessary in order to investigate the role of
      DEFB1 polymorphisms in diabetic periodontitis patients and the influence of the
      peptide in periodontal pathogens.

PMID- 27688369
TI  - Endodontic Management of the Three-Rooted Mandibular First Permanent Molar: a
      Case Report.
AB  - The distal root of the mandibular first permanent molar (MFPM) contains one or
      two canals. More rarely, the second/third distal canal is found in a separate
      root in a distolingual (DL) position - a radix entomolaris (RE). In Caucasians,
      this occurs in less than 4% of cases, but it is equally important to be aware of
      this possibility. Careful examination of the preoperative periapical radiographs
      (orthoradial and mesially angled) and inspection of the pulp chamber floor during
      endodontic management may indicate that this radicular variant is present. RE's
      lingual inclination and buccolingual curvature must be taken into account during
      cleaning and shaping of the canal within this root to avoid procedural errors,
      such as straightening and ledging of the root canal, perforation or instrument
      fracture. The aim of the present paper was to discuss a case report of a young
      patient, referred to an endodontic office after a ledge was created by
      inappropriate instrumentation of a buccolingually curved RE canal. 

PMID- 27688370
TI  - Topical Steroids and CO2 Laser in the Treatment of Refractory Oral Lichenoid Drug
      Reaction and Lichenoid Contact Lesion: a Case Report.
AB  - A 54-year-old female presented with severe pain on the gingiva and buccal mucosa.
      Oral findings revealed generalized fiery red gingiva, ulcerative with white
      striae covered by pseudo-membranes on both buccal mucosae. She had hypertension,
      dyslipidemia, subclinical hypothyroidism and arthritis. She was treated with
      atorvastatin, hydrochlorothiazide, valsartan, levothyroxine and non-steroidal
      anti-inflammatory drug (NSAIDs). Her oral lesions were a slight improvement from
      a previous treatment with pimecrolimus cream, triamcinolone acetonide 0.1%
      orabase and injection. After diclofenac was replaced with tenoxicam and oral
      lesions were treated with various topical steroids, the lesions showed marked
      improvement. The biopsy from the buccal mucosa revealed oral lichen planus. Patch
      test showed positivity to mercury, gold sodium thiosulfate and palladium. One
      year later the left buccal mucosa showed red, round papillomatous-like lesions.
      The histopathological report showed a non-specific ulcer with chronic
      inflammation. The lesions flared up after replacing amalgam with crowns. After
      CO2 laser treatment, the lesions showed some improvement. Direct and indirect
      immunofluorescence of the lesions proved to be negative. This first case report
      showed that the palliative treatment of refractory oral lichenoid lesions with
      potent topical steroids for 7 years had no side-effects. CO2 laser can be an
      alternative treatment of refractory lesion in this case. 

PMID- 27688371
TI  - Gingival necrosis due to the ill-fitting denture.
AB  - We present a case of an 80-year-old male who was referred to the Department of
      Oral Medicine, School of Dental Medicine University of Zagreb, Croatia due to
      gingival ulcer which was present for eight days. Clinical examination has
      revealed exposed bone on the toothless alveolar ridge in the lower molar region
      on the right side of 0.8 cm in diameter. Otherwise, the patient was taking
      doxazosin due to urinary problems and ipatropium bromide due to respiratory
      problems. The patient wore a 6-year-old partial lower denture. He was initially
      treated with periodontal bandage (Resopack, HagenWerken, Germany) for the first
      three days and was instructed not to wear the denture; however, no benefit could
      be seen. Therefore, we added a local corticosteroid (betamethasone) and am oral
      antiseptic (chlorhexidine digluconate) applied three times a day. After 3 weeks
      the lesion healed. A list of possible causative factors regarding gingival ulcers
      is included. 

PMID- 27688372
TI  - 50(th) Anniversary of the Central Dental Library of School of Dental Medicine
      University of Zagreb.
AB  - Libraries have an exceptional place in the history, culture, education and
      scientific life of a nation. They collect all aspects of our linguistics and
      literacy, all out theoretical assumptions as well as all the results of
      experience and practice. The importance of a library is not mirrored only in the
      national and historical role and heritage, but in a more permanent, informational
      role, since a modern library must, above all, be an effective information system.
      Since a library of a university operates as a part of its matrix, it is easily
      shadowed by other forms of educational and scientific infrastructure. 50(th)
      anniversary of the Central Dental Library of the School of Dental Medicine
      University of Zagreb is an excellent opportunity to make a call to the
      institution and public to its unique and irreplaceable role. 

PMID- 27688373
TI  - Alveolar Bone Grafting in Cleft Patients from Bone Defect to Dental Implants.
AB  - Cleft lip and palate is the most common congenital deformity affecting
      craniofacial structures. Orofacial clefts have great impact on the quality of
      life which includes aesthetics, function, psychological impact, dental
      development and facial growth. Incomplete fusion of facial prominences during the
      fourth to tenth week of gestation is the main cause. Cleft gaps are closed with
      alveolar bone grafts in surgical procedure called osteoplasty. Autogenic bone is
      taken from the iliac crest as the gold standard. The time of grafting can be
      divided into two stages: primary and secondary. The alveolar defect is usually
      reconstructured between 7 and 11 years and is often related to the development of
      the maxillary canine root. After successful osteoplasty, cleft defect is closed
      but there is still a lack of tooth. The space closure with orthodontic treatment
      has 50-75% success. If the orthodontic treatment is not possible, in order to
      replace the missing tooth there are three possibilities: adhesive bridgework,
      tooth transplantation and implants. Dental implant has the role of holding dental
      prosthesis, prevents pronounced bone atrophy and loads the augmentation material
      in the cleft area. Despite the fact that autologous bone from iliac crest is the
      gold standard, it is not a perfect source for reconstruction of the alveolar
      cleft. Bone morphogenic protein (BMP) is appropriate as an alternative graft
      material. The purpose of this review is to explain morphology of cleft defects,
      historical perspective, surgical techniques and possibilities of implant and
      prosthodontic rehabilitation. 

PMID- 27688374
TI  - The Level of Anxiety and Pain Perception of Endodontic Patients.
AB  - OBJECTIVES: to compare the level of anxiety reported by patients and assessed by
      dentists. Also, the expected and actual pain during the treatment perceived by
      the patient and dentist were assessed. METHODS: sixty six endodontic patients
      filled in two questionnaires, prior to and after the treatment, so did their
      therapists. The first set of questions for patients was regarding demographics,
      the frequency of dental visits, the level of anxiety and expectations about the
      level of pain. Before the treatment, dentists estimated the level of patients'
      anxiety and the expected intensity of pain. After the treatment, the patients
      evaluated the level of experienced pain and dentists' empathy during the
      treatment, while dentists reassessed the intensity of patients' pain.The data
      were statistically analysed by t-test for paired samples and by Spearmans's Rho
      correlation coefficient at level of significance set at 0.05. RESULTS: Patients'
      expectation of pain intensity was higher than the actual pain during the
      treatment (t-test=3.540, p=0.001). There was no difference in the level of pain
      which dentists expected and their perception of pain during the procedure. There
      was a statistically significant correlation between the patients' level of
      anxiety and recognition of it by dentists (Spearman Rho=0.460, p<0.001). A higher
      level of anxiety increased the expected intensity of pain (Spearman Rho=0.401,
      p=0.001). Actual intensity of pain was not significantly associated with dental
      anxiety (Spearman Rho=0.080, p=0.524). CONCLUSION: Since the level of dental
      anxiety was associated with the increased intensity of expected pain, a vicious
      cycle of pain and anxiety may be terminated by giving positive information to the
      patient before and during endodontic procedures.

PMID- 27688375
TI  - Atmospheric Pressure Plasma Jet as an Accelerator of Tooth Bleaching.
AB  - OBJECTIVE: To study the effect of atmospheric pressure plasma (APP) jet as a
      potential accelerator of the degradation of hydrogen peroxide in bleaching gels
      which could lead to better and faster bleaching. MATERIAL AND METHODS: 25
      pastilles of hydroxylapatite were colored in green tea for 8 hours and were
      randomly divided into five groups (n = 5). The bleaching process was performed
      with 30% and 40% hydrogen peroxide (HP) gel alone and in conjunction with helium
      APP jet. During the bleaching treatment, optical emission spectroscopy and non
      contact surface temperature measurement using pyrometer were performed. Color of
      the pastilles was determined by a red-green-blue (RGB) colorimeter. PH values of
      bleaching gels were measured before and after the plasma treatment on additional
      10 pastilles using a pH meter with contact pH electrode. RESULTS: The color
      measurements of pastilles before and after the treatment showed that treatment
      with APP jet improved the bleaching effect by 32% and 15% in the case of 30% and
      40% HP gel. Better results were obtained approximately six times faster than with
      a procedure suggested by the bleaching gel manufacturer. Optical emission
      spectroscopy proved that plasma has a chemically active role on the gel. After
      the APP treatment, pH values of bleaching gels dropped to about 50-75% of their
      initial value while the surface temperature increased by 8-10C above baseline.
      CONCLUSION: The use of plasma jet provides more effective bleaching results in a
      shorter period of time without a significant temperature increase which may cause
      damage of the surrounding tissue.

PMID- 27688376
TI  - The Effect of Repeated Microwaving Disinfection on the Dimensional Stability of
      Acrylic Dentures.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of repeated microwave
      disinfections on the dimensional stability of acrylic dentures. MATERIALS AND
      METHODS: Three groups of dentures made of a heat polymerized acrylic resin were
      tested. I: dentures kept in water (control group). II: dentures microwaved daily
      while being immersed into water (wet disinfection). III: dentures microwaved
      daily without being immersed into water (dry disinfection).?Measurements were
      taken across three reference points, on two occasions: after curing and immersion
      in water for 24 hours, and one week later.?Data obtained were analyzed using one
      way analysis of variance (ANOVA) and Scheffe's multiple range test. RESULTS: The
      results showed that the microwave disinfection provokes dimensional changes of
      the same pattern (shrinkage). The dentures which underwent wet disinfection
      exhibited the greatest shrinkage (p<0.05). CONCLUSIONS: Disinfection using
      microwave energy may cause dimensional changes (shrinkage) of complete
      dentures.?The microwave "dry disinfection" method can be safely applied in
      everyday practice since the dimensional changes which occurred seem to be of no
      clinical significance.

PMID- 27688377
TI  - Effects of Wire EDM on the Microstructure of P/M Titanium Samples.
AB  - PURPOSE: Commercially pure titanium (CP Ti) has been recognized in dentistry for
      its biocompatibility, good mechanical properties and corrosion resistance.
      Conventional manufacturing processes can affect surface quality and result in
      poor bonding of dental ceramics to CP Ti. This is why powder metallurgy (P/M) and
      wire electro-discharge machining (WEDM) are being introduced in the manufacturing
      process. The aim of this study was to evaluate the effect of WEDM on the surface
      composition and microstructure of P/M CP Ti samples produced for bond strength
      testing according to ISO 9693. MATERIALS AND METHODS: Eight samples of P/M CP Ti,
      dimensions according to ISO 9693, were made using WEDM and divided in two groups
      (untreated and grinded). Microanalyses of chemical composition and microstructure
      of both groups were made using SEM, EDS and XDR. RESULTS: SEM and EDS analysis of
      untreated samples showed a thin layer on surfaces with fractures in it. Grinded
      samples showed homogenous structure with no layer and no fractures. XDR analysis
      showed high level of oxides on the surface of untreated samples, while after
      grinding only pure alpha-phase was found. CONCLUSION: WEDM is a suitable method
      of sample production for ISO 9693 if accompanied by grinding with silicon carbide
      papers P320-P4000.

PMID- 27688378
TI  - Histochemistry and Immunohistochemistry Evaluation of the Abrikossoff's Tumour of
      the Tongue: a Case Report.
AB  - Abrikossoff's tumour is a rare benign soft tissue neoplasm that can occur in any
      part of the body, including the orofacial region. The tumour is usually benign,
      but there are reports of cases in which the tumour shows a locally aggressive
      behaviour, malignancy, and distant metastases. The aetiology is unknown, since
      several studies have shown that different cells are involved. In the present
      case, a 36-year-old Dominican woman was referred to the Department of Oral and
      Maxillofacial Surgery in Policlinico Federico II, Naples with a circumscribed
      lesion and sessile nodule on the dorsum of the tongue measuring about 17 mm in
      diameter. The treatment consisted of an excisional biopsy performed on the basis
      of the diagnostic hypothesis of Abrikossoff's tumour, which was confirmed by
      histopathological analysis and histochemistry and immunohistochemistry
      evaluation. Abrikossoff's tumour is an uncommon neoplasm which must be carefully
      diagnosed considering all the histological and clinical aspects in order to be
      treated correctly. 

PMID- 27688379
TI  - Epidermoid Cyst Arising in the Buccal Mucosa: Case Report and Literature Review.
AB  - Epidermoid cysts are benign subcutaneous lesions, and the large majority of these
      cysts affect the floor of the mouth; however, the buccal mucosa is not the usual
      site of occurrence. To date, only 5 articles have been published with 6 cases of
      epidermoid cysts arising in the buccal mucosa. Therefore, the aim of this study
      was to describe the clinical, histopathological and immunohistochemical features
      of a case of an epidermoid cyst located in the buccal mucosa. To our knowledge,
      this is the first report of an oral epidermoid cyst describing an intense foreign
      body gigantocellular inflammatory reaction against epithelial keratin component.
      Although the usual diagnosis for epidermoid cysts is based on histopathological
      findings, this case report addresses novel information regarding the
      immunohistochemical pattern which may be found in these lesions. 

PMID- 27688380
TI  - Dental Ritual Mutilations and Forensic Odontologist Practice: a Review of the
      Literature.
AB  - BACKGROUND: Ethnic mutilations have a social and anthropological significance
      both in contemporary and past human behavior, influenced by geographic, religious
      and cultural factors which can greatly help forensic odontologist's practice in
      dental profiling process.?Dental ritual mutilations and dental decorations were -
      and still are - practiced among many ethnic groups and cultures. Throughout the
      history of humanity, having healthy teeth has a symbolic meaning of youth, beauty
      and strength, but it can also have other meanings.?Dental ritual mutilations were
      documented in many cultures in the past and were practiced mainly for religious
      rituals purposes, for esthetic reasons and because they represented a symbol of
      status or of belonging to a particular social group. Similar rituals are still
      performed. MATERIAL AND METHOD: The present paper is a systematic review of the
      literature reporting on dental ritual mutilations from the early 1960s and is
      included in Pubmed, Scopus and Googlescholar. The research was deliberately
      limited only to the ritual mutilations, which can be defined as "any irreversible
      impairment of the integrity of the human organism, made with a ritual purpose and
      without any curative aim". Therefore all the articles dealing with single or
      multiple dental self extractions of psychotic origins were excluded, as well as
      the infant oral mutilations, since the practice is deemed to have therapeutical
      effects among ethnic groups dedited to this practice. CONCLUSIONS: The knowledge
      of dental alteration due to oral mutilations can be a powerful tool for the
      identification procedures of living or dead persons or even in human remains
      especially providing relevant information about the ethnic origins and the
      cultural background of a subject. Some medical legal issues for the odontologist
      about dental mutilation are also addressed in the paper.

PMID- 27688381
TI  - Periodontal Disease and its Association with Angiographically Verified Coronary
      Artery Disease.
AB  - PURPOSE: The aim of this research was to investigate the association of chronic
      and aggressive periodontitis with the severity of coronary artery disease which
      was angiographically verified. MATERIAL AND METHODS: Subjects were selected among
      the hospitalized patients at the University Hospital Centre Zagreb who had
      coronary angiography done because of the chest pain. Thorough clinical
      examination included periodontal indices and clinical and socio-demographic
      characteristics of participants. Subjects were divided in two test groups, acute
      coronary syndrome (ACS) and stable coronary artery disease (CAD), and the control
      group with no significant CAD. Data were analyzed using Kruskal-Wallis and
      Pearson's Chi-Square test. RESULTS: From 106 subjects, 66 (62.3%) were
      hospitalized for ACS, 22 (20.7%) had stable CAD and only 18 (17.0%) had no
      significant CAD. Only 26 (24.5%) out of 106 patients were never smokers (p<0.05).
      Chronic periodontitis was the most common finding with 68.2% in ACS group and
      54.5% in stable CAD group, while healthy patients without periodontitis (72.6%)
      were dominant in the control group (p<0.001). Stable CAD group had the highest
      mean probing depth (PD) 3.92+/-1.16, gingival recession (GR) 1.34+/-0.78,
      clinical attachment level (CAL) 4.60+/-1.41 and bleeding on probing (BOP) 45.98+/
      26.19 values, whereas ACS group had mean PD value of 3.77+/-0.91, GR 1.11+/-0.66,
      CAL 4.32+/-1.08 and BOP 41.30+/-22.09, and no significant CAD group had mean PD
      value of 3.27+/-0.97, GR 0.69+/-0.37, CAL 3.62+/-1.04 and BOP 26.39+/-13.92
      (p<0.05). CONCLUSION: Periodontitis was shown to be associated with
      angiographically verified coronary artery disease. Physical inactivity, poor oral
      hygiene and periodontal inflammation were observed in patients with ACS and
      stable CAD.

PMID- 27688382
TI  - A Quantitative Analysis of a Probiotic Storage Media for Avulsed Teeth.
AB  - AIM: The aim of the present in vitro study was to investigate the potential of a
      storage medium, probiotic yogurt (Bifidibacterium animalis DN 173010) in
      comparison with Hank's balanced salt solution (HBSS), saline and milk in
      maintaining viable periodontal ligament (PDL) cells on simulated avulsed teeth.
      MATERIALS AND METHODS: Thirty-six freshly extracted single-rooted human teeth
      with closed apices were divided into six experimental groups (N=6). The teeth
      were extracted as atraumatically as possible and washed in sterile saline
      solution to eliminate residual blood. Following extractions, the coronal 3 mm of
      PDL tissues were scraped with a #15 scalpel to remove cells that may have been
      damaged. The positive and negative controls corresponded to 0 minutes and an 8
      hour dry time, respectively. After extraction, the positive control teeth were
      immediately treated with dispase and collagenase. The negative control teeth were
      bench-dried for 8 h, with no follow-up storage solution time, and then placed in
      the dispase and collagenase. The number of viable protective least significant
      difference PDL cells were counted under a light microscope with a hemocytometer
      at 20* magnification and analyzed. Statistical analysis of the data was
      accomplished using Nonparametric ANOVA complemented by Kruskal-Wallis Test and
      Dunn's Multiple Comparisons Test. RESULTS: Positive control was found to be
      significantly better than the others, there were statistically significant
      differences between positive control and other test groups (p=0.000). The teeth
      stored in positive control demonstrated the highest number of viable PDL cells
      followed in order by probiotic yogurt, HBSS, saline and milk. CONCLUSION:
      Bifidibacterium animalis DN 173010 seems to be an alternative for the temporary
      storage of avulsed teeth, due to high number of viable PDL cells. Probiotics may
      be suitable transport media for avulsed teeth, but further research is warranted
      using the commercially available products.

PMID- 27688383
TI  - Analysis of Translucency Parameter of Glass-Ceramics Fabricated by Different
      Techniques.
AB  - THE PURPOSE: of the study was to analyse translucency parameter (TP values) of
      glass-ceramics fabricated by different techniques and investigate the effect of
      the corrosive medium on TP values. MATERIALS AND METHODS: Three specimens of each
      type of IPS e.max ceramics (Ivoclar Vivadent, Schaan, Liechtenstein) were made in
      three colours (A2, C2 and B3) by three fabrication techniques (layering - e.max
      Ceram Dentin; heat-pressing - e.max Press; CAD/CAM - e.max CAD). Specimens were
      made in the form of plates (10 mm x 12 mm x 0.8 mm). CIE L*a*b* values were
      measured by a spectrophotometer (X-Rite DTP 20 Pulse, Neu Isenburg, Germany)
      before and after exposure to 4% acetic acid at 80  degrees C for 16 hours (ISO
      6872) to calculate translucency parameter (TP values). Statistical data were
      analysed using the IBM SPSS 22 software. RESULTS: IPS e.max Ceram Dentin had
      significantly the lowest TP values, and IPS e.max Press the highest TP values of
      all colours (A2, C2, B3), both prior and after exposure to acid (p<0.001). The
      difference in TP values among colours was evident in the IPS e.max Ceram Dentin
      material, both before and after exposure to acid with a great effect size
      (p<0.001; eta2 = 0.702 and 0.741), and in the IPS e.max Press material (p<0.001,
      effect size 0.547 and 0.576). CAD/CAD specimens showed uniform TP values between
      three colours. Further, exposure to a corrosive medium did not result in a
      statistically significant change of TP values in any of the materials tested.
      CONCLUSIONS: Different types of glass-ceramics showed significant difference in
      TP values both with respect to the fabrication technique and colour. Exposure to
      a corrosive medium did not result in a statistically significant change of TP
      values.

PMID- 27688384
TI  - Influence of the Hinge Axis Transfer Modality on the Three-Dimensional Condylar
      Shift Between the Centric Relation and the Maximum Intercuspation Positions.
AB  - PURPOSE: The purpose of the study was to determine whether the hinge axis
      registration and the transfer modality (facebow transfer vs. average mounting)
      from the subject to the articulator affect the three-dimensional condylar shift
      between the centric relation (CR) and the maximum intercuspation (MI) position.
      MATERIAL AND METHODS: The study was comprised of 32 fully dentate subjects (16
      male and 16 female). Only the asymptomatic participants with normal occlusal
      relations (Angle class I) aged 20 - 33 (mean age 22.6 +/- 4.7) met the inclusion
      criteria. Three-dimensional condylar shift (anteroposterior, superoinferior and
      mediolateral shift) between the centric relation position (CR) and the maximum
      intercuspation (MI) position was analyzed by means of Mandibular Position
      Indicator (SAM Prazisionstechnik GmbH, Muenchen, Germany). RESULTS: The average
      three-dimensional condylar shift was 0.13 +/- 0.12 mm for facebow transfer and
      0.22 +/- 0.23 mm for average mounting. There were no statistically significant
      differences noted between genders. The results of the Mann-Whitney test showed
      statistically significant differences for anteroposterior and superoinferior
      condylar shift (P < 0.001). However, the difference in the mediolateral shift was
      not statistically significant. CONCLUSIONS: In order to find discrepancies within
      the three-dimensional condylar shift, facebow transfer proved to be more accurate
      than the average mounting in the semi-adjustable articulator. However, the
      average value of three-dimensional shifts of the condyle did not differ from
      normal values and they did not have clinical significance. Thus, both ways of
      transfer modalities (facebow transfer and average mounting) in asymptomatic
      subjects with normal occlusion can be considered reliable.

PMID- 27688386
TI  - Posttraumatic Stress Disorder and Orofacial Pain.
AB  - Chronic orofacial pain occurs frequently in patients with posttraumatic stress
      disorder (PTSD) and at the same time any pathological process involving orofacial
      area can be reflected in emotional interpretation of pain and can trigger a
      series of reactions associated with the PTSD group of symptoms in patients with
      PTSD. Painful stimuli caused in this way may occur after the primary cause
      ceased, and because of convergence can cause referred pain outside of the
      anatomical site where the primary injury occurred. Chronic orofacial pain and
      PTSD are diagnosed on the basis of subjective testimony and this regularly occurs
      in the context of social interaction between patients, doctors, medical staff or
      researchers making it difficult to standardize the results and introduces many
      cultural phenomena. 

PMID- 27688385
TI  - Functional Impressions in Complete Denture and Overdenture Treatment.
AB  - Tooth loss can cause loss of occlusal, masticatory, esthetic, physiognomic,
      phonetic and psychosocial function of patients. The most frequently used
      treatment method of completely edentulous patients and patients with a small
      number of remaining teeth are complete dentures or overdentures. One of the most
      important clinical and laboratory procedures in their fabrication is functional
      impression taking. The aim of this paper was to present procedures of taking
      functional impressions in fabrication of complete dentures and overdentures,
      using standardized techniques and materials. An accurate functional impression
      together with other correctly performed clinical and laboratory procedures ensure
      good retention and stability of dentures, which is a precondition for restoring
      patients' lost functions. 

PMID- 27688387
TI  - Craniofacial Fibrous Dysplasia in an Elderly Patient: A Case Report with a Review
      of Literature.
AB  - Fibrous dysplasia is a benign fibro-osseous disorder, characterized by fibrous
      connective tissue containing abnormal bone which replaces normal bone. It
      represents 2 to 5% of all bone tumors and 7% of all benign tumors. Most commonly
      it affects younger age groups, with a higher prevalence in the maxilla than the
      mandible. It is a lesion of unknown etiology, uncertain pathogenesis, and diverse
      histopathology. Fibrous dysplasia can involve multiple bones (polyostotic) or a
      single bone (monostotic). The lesions of fibrous dysplasia can be surgically
      recontoured for esthetic or functional purposes once the growth ceases. Here we
      report a case of craniofacial fibrous dysplasia in an 83-year-old elderly male
      patient with emphasis on radiographic features. 

PMID- 27688389
TI  - 10(th) Anniversary of Acta stomatologica Croatica Online?ISSN 1846-0410.

PMID- 27688388
TI  - Epidermoid Cyst Arising in the Buccal Mucosa: Case Report and Literature Review.
AB  - Epidermoid cysts are benign subcutaneous lesions, and the large majority of these
      cysts affect the floor of the mouth; however, the buccal mucosa is not a usual
      site of occurrence. To date, only 5 articles have been published with 6 cases of
      epidermoid cysts arising in the buccal mucosa. Therefore, the aim of this study
      was to describe the clinical, histopathological and immunohistochemical features
      of a case of epidermoid cyst located in the buccal mucosa. To our knowledge, this
      is the first report of an oral epidermoid cyst describing an intense foreign body
      gigantocellular inflammatory reaction against epithelial keratin component.
      Although the usual diagnosis for epidermoid cysts is based on histopathological
      findings, this case report addresses novel information regarding to the
      immunohistochemical pattern that may be found in these lesions. 

PMID- 27688390
TI  - Presentation of Certain Parameters Found In 2009-2013 Annual Dental Medicine
      Reports.
AB  - The Croatian Institute of Public Health (CIPH) collects health care related
      statistical data based on the Republic of Croatia's Annual Plan of Implementation
      of Statistical Activities. The purpose of this study was to analyse the CIPH data
      retrieved from annual reports, obtained from contractual teams and institutions
      related to dental medicine activities, collected in respective counties and for
      the entire country. MATERIAL AND METHODS: The data were collected from the
      Croatian Statistical Health Care Yearbook for the period from 2009 to 2013.
      RESULTS: The analysis has shown the increase in the number of insured persons
      (5%), but the decrease in the number of persons who received care (10%) and the
      increase in the number of visits (14%) and general examinations (13%). The
      majority of the beneficiaries were from the City of Zagreb with the highest
      number of visits, but with a low number of general examinations included in these
      visits (11%); while the Zadar County had the highest number of general
      examinations in terms of dental health care users (90.6%) and the proportion of
      general examinations in visits (30%). The most common diagnosis was dental caries
      (43%). The incomplete and insufficient reporting from some counties, inadequate
      recording of diagnoses and of curative and preventive procedures could be the
      factors affecting the quantity and quality of obtained data. Proper and regular
      submissions of reports to counties' public health institutes, regular preventive
      examinations, adequate recording of diagnoses and procedures would contribute
      positively to further health planning and the implementation of preventive
      measures for the improvement of oral health. CONCLUSION: The data analysis gives
      an insight into the current situation allowing on such basis further planning and
      conducting of activities at national and local level. Further analyses would help
      to get a better perspective and improvement of dental medicine activities.

PMID- 27688391
TI  - The Oral Status of Adult Population in the Croatian Town of Knin: a Cross
      Sectional Study.
AB  - THE AIM: Epidemiologic studies in many countries show uneven distribution of oral
      diseases (primarily caries) within the population. This is why more studies are
      oriented towards specific regions or subpopulations instead of large scale
      national surveys. The major purpose of this cross sectional study was to obtain
      relevant data about the oral status of the population of Knin and its
      surroundings according to the WHO criteria. SUBJECTS AND METHODS: The study
      included 414 participants aged between 18 and 65. The recorded variables included
      general anamnestic data, extraoral status, oral mucosa status, temporomandibular
      joint status, dental, periodontal and prosthetic status, and the need for dental
      restoration. The comparison between different groups regarding age, gender,
      educational level and origin was made. RESULTS: DMFT index was 17.3 - with on
      average 1.7 caries, 6.2 fillings, and 9.4 teeth extracted. SiC index equaled
      26.4. The difference was significant regarding the level of education and age
      (p<0.001). The percentages of individuals with the highest CPI scores from 0-4
      were 27.3, 16.9, 36.5, 16.4 and 2.9%, respectively. The difference between the
      age groups in CPI scores was statistically significant, while the differences
      according to the gender and origin were not significant (p=0.001). CONCLUSION:
      The population of Knin and the surrounding area exhibited very bad oral status
      which can be attributed to the consequences of the war in the 1990-ies, the
      economic transition, and the lack of national program for oral health promotion.

PMID- 27688392
TI  - Antimicrobial Capacity of Casein Phosphopeptide/Amorphous Calcium Phosphate and
      Enzymes in Glass Ionomer Cement in Dentin Carious Lesions.
AB  - OBJECTIVE: To evaluate the ability of casein phosphopeptide/amorphous calcium
      phosphate (CPP/ACP) and lysozyme, lactoferrin, and lactoperoxidase (LLL) added to
      glass ionomer cement (GIC) to inhibit the growth of S. mutans in a caries model.
      MATERIAL AND METHODS: Eighty permanent third molars were selected. The dentin of
      these teeth was exposed and flattened. Except for the coronal dentin, the
      specimens were waterproofed, autoclaved, and submitted to cariogenic challenge
      with standard strain of S. mutans. The carious lesions were sealed as follows:
      group 1 (n=20): GIC without additives; group 2 (n=20): GIC + CPP/ACP; group 3
      (n=20): GIC + LLL; group 4 (n=20): GIC + CPP/ACP + LLL. S. mutans counts were
      performed before the caries were sealed (n=5), after 24 hours (n=5), at 1 month
      (n=5), and at 6 months (n=5). The results were analyzed using descriptive
      statistical analysis and the Kruskal-Wallis test (Student-Newman-Keuls test).
      RESULTS: GIC + LLL caused a significant reduction of S. mutans 1 month after
      sealing (p<0.01); however, there was a significant growth of S. mutans 6 months
      after sealing. GIC, GIC + CPP/ACP, and GIC + CPP/ACP + LLL showed similar
      behavior with significant reduction of S. mutans after 24 hours (p<0.05) and
      increase after 1 and 6 months. CONCLUSION: The addition of LLL to GIC increases
      the antimicrobial action of GIC on S. mutans. This leads to control of bacterial
      biofilm for 1 month, thus stopping the progression of carious lesions.

PMID- 27688393
TI  - In Vivo and in Vitro Evaluations of Repeatability and Accuracy of VITA
      Easyshade(r) Advance 4.0 Dental Shade-Matching Device.
AB  - OBJECTIVES: The objective of this study was to evaluate the intra-device
      repeatability and accuracy of dental shade-matching device (VITA Easyshade(r)
      Advance 4.0) using both in vitro and in vivo models. MATERIALS AND METHODS: For
      the repeatability assessment, the in vivo model utilized shade-matching device to
      measure the central region of the labial surface of right maxillary central
      incisors of 10 people twice. The following tooth colors were measured: B1, A1,
      A2, A3, C1 and C3. The in vitro model included the same six Vitapan Classical
      tabs. Two measurements were made of the central region of each shade tab. For the
      accuracy assessment, each shade tab from 3 Vitapan Classical shade guides was
      measured once. CIE L*a*b* values were determined. Intraclass correlation
      coefficients (ICCs) were used to analyze the in vitro and in vivo intra-device
      repeatability of the shade-matching device. The difference between in vitro and
      in vivo models was analyzed. Accuracy of the device tested was calculated.
      RESULTS: The mean color differences for in vivo and in vitro models were 3.51 and
      1.25 E units, respectively. The device repeatability ICCs for in vivo
      measurements ranged from 0.858 to 0.971 and for in vitro from 0.992 to 0.994.
      Accuracy of the device tested was 93.75%. CONCLUSION: Within the limitations of
      the experiment, VITA Easyshade(r)Advance 4.0 dental shade-matching device enabled
      reliable and accurate measurement. It can be a valuable tool for the
      determination of tooth colours.

PMID- 27688394
TI  - Mandibular Range of Movement and Pain Intensity in Patients with Anterior Disc
      Displacement without Reduction.
AB  - OBJECTIVE: Temporomandibular disorders (TMD) are the most common source of
      orofacial pain of a non-dental origin. The study was performed to investigate the
      therapeutic effect of the conventional occlusal splint therapy and the physical
      therapy. The hypothesis tested was that the simultaneous use of occlusal splint
      and physical therapy is an effective method for treatment of anterior disc
      displacement without reduction. MATERIALS AND METHODS: Twelve patients (mean age
      =30.5 y) with anterior disc displacement without reduction (according to RDC/TMD
      and confirmed by magnetic resonance imaging) were randomly allocated into 2
      groups: 6 received stabilization splint (SS) and 6 received both physical therapy
      and stabilization splint (SS&PT). Treatment outcomes included pain-free opening
      (MCO), maximum assisted opening (MAO), path of mouth opening and pain as reported
      on visual analogue scale (VAS). RESULTS: At baseline of treatment there were no
      significant differences among the groups for VAS scores, as well as for the range
      of mandibular movement. VAS scores improved significantly over time for the SS&PT
      group (F=28.964, p=0.0001, effect size =0.853) and SS group (F=8.794, p=0.001,
      effect size =0.638). The range of mouth opening improved significantly only in
      the SS&PT group (MCO: F=20.971, p=0.006; MAO: F=24.014, p=0.004) (Figure 2).
      Changes in path of mouth opening differ significantly between the groups
      (p=0.040). Only 1 patient in SS&PT group still presented deviations in mouth
      opening after completed therapy while in the SS group deviations were present in
      5 patients after completed therapy. CONCLUSION: This limited study gave evidence
      that during the treatment period lasting for 6 months, the simultaneous use of
      stabilization splint and physical therapy was more efficient in reducing
      deviations and improving range of mouth opening than the stabilization splint
      used alone. Both treatment options were efficient in reducing pain in patients
      with anterior disc displacement without reduction. Despite of objectively
      diagnosed disruption of temporomandibular joint anatomy, physiological function
      was regained.

PMID- 27688395
TI  - Radiographic Evaluation of Crestal Bone Loss Around Dental Implants in Maxilla
      and Mandible: One Year Prospective Clinical Study.
AB  - PURPOSE: The aim of the study was to analyze the amount of maxillary and
      mandibular crestal bone loss around Bredent Sky Blue type of implants of
      different dimensions one year after implantation. MATERIALS AND METHODS: 36
      implants of diameter 3.5 x 10 mm were inserted in the maxilla and 12 in the
      mandible. 52 implants of diameter 4.0 x 8 mm were inserted in the maxilla, and 61
      in the mandible (two-stage implant surgery). RESULTS: No statistically
      significant differences were found between the right and left side of the maxilla
      and between the right and left side of the mandible at the implant sites
      regarding distal and mesial bone losses as shown by analysis of variance (ANOVA).
      CONCLUSION: Statistically significant differences were found between anterior
      maxilla, posterior maxilla and anterior mandible and posterior mandible at
      implant sites regarding distal and mesial bone losses as shown by analysis of
      variance (ANOVA).

PMID- 27688397
TI  - A Fixed Telescopic Prosthesis Designed to Retrieve and Convert to Fixed-Removable
      Combination Case: A Clinical Report.
AB  - This clinical report describes a fixed maxillary telescopic dental prosthesis
      (FTDP) employing milled base metal copings and a metal superstructure veneered
      with composite resin, for the restoration in a periodontally compromised patient
      with uncontrolled diabetes. The telescopic prosthesis framework design
      incorporated occlusal rest seats in key positions along the arch in case of
      future posterior tooth loss, in order to be converted to fixed - removable
      combination prosthesis. The mandible was restored with a conventional fixed
      ceramo-metal dental prosthesis. 

PMID- 27688396
TI  - New Knowledge about Zirconium-Ceramic as a Structural Material in Fixed
      Prosthodontics.
AB  - Dental ceramics represents a major structural material in fixed prosthodontics.
      Increasing demands for esthetics led to development of new ceramic materials in
      order to eliminate the use of metal framework and for all ceramic restorations
      with mechanical properties to withstand high occlusal forces. Out of all the
      present ceramic materials, zirconium-ceramic has the best mechanical properties,
      and is the only material that can be used for longer span fixed dental
      restorations. Despite its excellent mechanical properties, to achieve great
      esthetics, due to absence of translucency, zirconium-dioxide cannot be used as a
      single material and needs veneering with more esthetic ceramic. When introduced
      in dental medicine, it was considered an almost ideal material for fixed
      prosthodontics, but clinical use and in vivo and in vitro studies showed many
      problems which still persist despite the improvements.?This review aims to reveal
      new developments in zirconium-ceramics and technical procedures which could
      increase clinical performance and longevity of these restorations. 

PMID- 27688398
TI  - Severe Generalized Periodontitis in a Patient with an Aplastic Anemia: a 5 Year
      Follow-up Case Report.
AB  - Aplastic anemia is a hematological disorder characterized by pancytopenia. This
      case report presents a young patient with untreated periodontitis associated with
      hematological disorders, and cyclosporine therapy. During 2 consecutive days,
      periodontal therapy which consisted of nonsurgical therapy supplemented with an
      antibiotic treatment and antifibrinolytic therapy was performed. Commercial
      microbiological PCR tests and periodontitis IL-1 polymorphism risk test were
      performed. Following the periodontal therapy, the inflammation was resolved and
      the patient's occlusion was restored by means of removable partial dentures.
      After the 5 year follow-up, the patient still remained with shallow probing
      depths although there was inadequate compliance during the maintenance phase.
      Aplastic anemia increases the risk of onset of severe forms of periodontitis that
      can be additionally complicated with cyclosporine therapy. In such patients,
      periodontal therapy must be supplemented with antibiotics. 

PMID- 27688399
TI  - Cystic Shape Cemento-Ossifying Fibroma of Ethmoid Sinus.
AB  - Cemento-ossifying fibromas are a group of rarely occurring benign tumours,
      developing from the periodontal membrane and varying considerably in appearance
      and in the progress of the disease. Their common feature is higher or lower
      production of cemental tissue. In most cases the tumours are small because their
      cementoma mature quickly and become inactive, which causes the tumour to stop
      growing. They develop most frequently in the mandible and also in the maxilla.
      Other sites, such as paranasal cavities, soft tissues and bones of the head, are
      extremely rare. The case of a cemento-fibrosing tumour with psammoma
      infiltrations, developing from the ethmoid sinus in a nine-year-old girl is
      reported. Due to frontal headaches and sight defects as well as impaired vision
      on the right side, NMR was done, which showed a mucocele of the front and rear
      ethmoid with destruction of the orbital wall and a breakthrough into the orbit.
      The right maxillary sinus showed a visible retention and a thickened mucous
      membrane. A rhinoscopy revealed a ball-shaped spherical mass in the medial nasal
      meatus, which was defined as concha bullosa. An endoscopic examination showed
      that the tumour protruded in front of the medium nasal concha into the right
      nasal cavity, softened the ethmoid roof, penetrated toward the base of the skull,
      adhered and pushed the orbit. It was removed by FESS technique, and PHD revealed
      subsequently that it was not a mucocele but a cemento-ossifying fibroma. 

PMID- 27688400
TI  - Neuron type-specific miRNA represses two broadly expressed genes to modulate an
      avoidance behavior in C. elegans.
AB  - Two broad gene classes are distinguished within multicellular organisms: cell
      type-specific genes, which confer particular cellular properties, and ubiquitous
      genes that support general cellular functions. However, certain so-called
      ubiquitous genes show functionally relevant cell type-specific repression. How
      such repression is achieved is poorly understood. MicroRNAs (miRNAs) are
      repressors, many of which are expressed with high cell type specificity. Here we
      show that mir-791, expressed exclusively in the CO2-sensing neurons in
      Caenorhabditis elegans, represses two otherwise broadly expressed genes. This
      repression is necessary for normal neuronal function and behavior of the animals
      toward CO2 miRNA-mediated repression of broadly transcribed genes is a previously
      unappreciated strategy for cellular specialization.

PMID- 27688403
TI  - In Vitro Evaluation and Comparison of the Translucency of Two Different All
      Ceramic Systems.
AB  - OBJECTIVES: The aim of this study was to evaluate and compare the translucency of
      two different all-ceramic systems using Vita Easyshade digital shade matching
      device in an in vitro model. MATERIALS AND METHODS: Translucency of lithium
      disilicate glass-ceramic (IPS e.max Press) and zirconia all-ceramic system
      (Ceramill ZI) were evaluated and compared. A total of 5 square-shaped specimens
      with 0.5 mm thickness were fabricated from each ceramic system in A1 shade
      according to Vitapan Classical shade tab. Specimens were then veneered and glazed
      with corresponding veneer ceramics recommended by each system manufacturer and
      the total thickness was set to 1.5 mm. Translucency was evaluated using VITA
      Easyshade in two stages: before and after veneering and glazing on black and
      white background. Translucency parameter (TP) was calculated. A one-way ANOVA and
      Bonferonni tests were used when appropriate (alpha=0.05). RESULTS: Lithium
      disilicate glass-ceramic was significantly more translucent than the zirconia
      system in both stages (P<0.05). Translucency of all specimens was significantly
      decreased after veneering and glazing in both all-ceramic systems (P<0.05).
      CONCLUSION: The translucency of two different dental ceramics was significantly
      influenced by both material and stages of preparation. Within the limitations of
      the experiment, these results can be valuable and help the clinician to make
      appropriate esthetic decisions.

PMID- 27688402
TI  - E2F coregulates an essential HSF developmental program that is distinct from the
      heat-shock response.
AB  - Heat-shock factor (HSF) is the master transcriptional regulator of the heat-shock
      response (HSR) and is essential for stress resilience. HSF is also required for
      metazoan development; however, its function and regulation in this process are
      poorly understood. Here, we characterize the genomic distribution and
      transcriptional activity of Caenorhabditis elegans HSF-1 during larval
      development and show that the developmental HSF-1 transcriptional program is
      distinct from the HSR. HSF-1 developmental activation requires binding of E2F/DP
      to a GC-rich motif that facilitates HSF-1 binding to a heat-shock element (HSE)
      that is degenerate from the consensus HSE sequence and adjacent to the E2F
      binding site at promoters. In contrast, induction of the HSR is independent of
      these promoter elements or E2F/DP and instead requires a distinct set of tandem
      canonical HSEs. Together, E2F and HSF-1 directly regulate a gene network,
      including a specific subset of chaperones, to promote protein biogenesis and
      anabolic metabolism, which are essential in development.

PMID- 27688404
TI  - The Oral Cavity State in Renal Transplant Recipients.
AB  - AIM: Patients with a solid organ transplant can have many different complications
      in the mouth, as a result of immunosuppression and side effects of drugs. The aim
      of this study was to examine the frequency and type of oral lesions in renal
      transplant patients, dental status, oral hygiene, oral lesions related to drugs
      which patients take and the time of transplantation as well as the frequency of
      patient's visits to the dentist in the post-transplant period. MATERIAL AND
      METHODS: The study was performed in a period of two years and included 100
      subjects with a renal transplant during their regular control visits to the
      Department of Nephrology and Dialysis, Clinical Hospital Centre Zagreb and the
      Department of Oral Medicine, School of Dental Medicine, University of Zagreb and
      100 randomly selected control subjects at the Department of Endodontics and
      Restorative Dentistry, School of Dental Medicine, University of Zagreb. RESULTS:
      Results showed a significantly higher incidence of oral lesions in patients with
      renal transplant (31%) compared to control subjects. The most frequent were
      erythematous (inflammatory changes), keratotic lesions and gingival hyperplasia.
      The average DMFT index was significantly lower in patients with renal transplant
      than in the control group. One third of patients had a subjective feeling of dry
      mouth. Oral hygiene was poor overall, and only a small number of subjects used
      the additional sustainers for oral hygiene. Most patients did not visit the
      dentist after the transplantation. CONCLUSION: Renal transplant patients need a
      comprehensive and regular dental care during the pre- and post-transplant period
      and a doctor of dental medicine should be part of a multidisciplinary team of
      medical specialists.

PMID- 27688401
TI  - Functional interplay between Mediator and TFIIB in preinitiation complex assembly
      in relation to promoter architecture.
AB  - Mediator is a large coregulator complex conserved from yeast to humans and
      involved in many human diseases, including cancers. Together with general
      transcription factors, it stimulates preinitiation complex (PIC) formation and
      activates RNA polymerase II (Pol II) transcription. In this study, we analyzed
      how Mediator acts in PIC assembly using in vivo, in vitro, and in silico
      approaches. We revealed an essential function of the Mediator middle module
      exerted through its Med10 subunit, implicating a key interaction between Mediator
      and TFIIB. We showed that this Mediator-TFIIB link has a global role on PIC
      assembly genome-wide. Moreover, the amplitude of Mediator's effect on PIC
      formation is gene-dependent and is related to the promoter architecture in terms
      of TATA elements, nucleosome occupancy, and dynamics. This study thus provides
      mechanistic insights into the coordinated function of Mediator and TFIIB in PIC
      assembly in different chromatin contexts.

PMID- 27688405
TI  - Folate and Vitamin B12 Levels in Thai Patients with Oral Lichenoid Related Drug.
AB  - BACKGROUND: Medications have been increasingly used by patients for the treatment
      of their systemic diseases. However, many drugs are reported to induce oral
      lichenoid lesions (OLL). AIM: The aim of our study was to investigate the
      relationship between OLL, medications, and folate and vitamin B12 levels.
      MATERIAL AND METHODS: Twenty Thai patients who were diagnosed with OLL by
      clinical and histopathological examination were included in this study. These
      subjects were compared with 24 healthy control subjects. Complete blood counts,
      hemoglobin typing, serum and red cell folate, and serum vitamin B12 levels were
      investigated. The medications taken and the systemic diseases of the Thai
      patients with OLL were recorded and analyzed. RESULTS: Our results showed that
      only 1/20 patients with OLL (5%) had low red cell folate and only 1 case showed a
      low level of serum folate. Vitamin B12 levels were within normal range in both
      groups. There were no significant differences in red cell folate, serum folate,
      or vitamin B12 levels between the patients with OLL and the control group
      (p>0.05). Four cases in OLL and 3 cases in the control group had low hematocrit
      less than 36% and they were defined as anemic. CONCLUSION: Antihypertensives and
      hypolipidemics were the most common medications taken by patients with OLL;
      however, these drugs had no effect on red cell folate, serum folate, or vitamin
      B12 levels. Since the patients were taking multiple drugs and we could not
      confirm the diagnosis of OLDR by withdrawal of the drugs, we used the term OLL
      related drug instead.

PMID- 27688406
TI  - The Effect of Salivary Calcium and Fluoride Toothpaste on the Formation of KOH
      Soluble Fluoride: In Vitro Study.
AB  - OBJECTIVE: The aim of this in vitro preliminary study was to assess the effect of
      smokers' saliva (assuming their higher calcium concentration) in combination with
      fluoridated toothpaste on the enamel uptake of alkali-soluble (KOH-soluble)
      fluoride. MATERIALS AND METHODS: Four enamel slabs were cut from each of 14
      impacted third molars and randomly assigned into 4 groups. Unstimulated saliva
      samples were collected from two age and sex matched volunteers. One of the
      samples was taken from a heavy smoker and the other sample was taken from a non
      smoker. Two groups (A and B) were shaken in saliva (A in smoker's saliva, B in
      nonsmoker's saliva) for 5 min and then shaken for 3 min in a toothpaste/deionized
      water slurry (1:3 w/w). One of the groups (group C) received no saliva treatment
      and was only shaken in toothpaste slurry for 3 min. The treatment was repeated
      after a 6-hour period. One of the groups (D) served as a control group with no
      treatment. RESULTS: Calcium concentration in the smoker's saliva was higher than
      in the nonsmoker's saliva. The enamel uptake of KOH-soluble fluoride in group A
      was significantly higher than that in the other two treatment groups, B and C.
      The enamel uptake of KOH-soluble fluoride in all 3 groups was statistically
      different from that in the control group. CONCLUSION: These results demonstrate
      that saliva collected from a heavy smoker, which had higher salivary calcium
      concentration, enhances enamel uptake of alkali-soluble fluoride and encourages
      us to conduct a large-scale study.

PMID- 27688407
TI  - Measurements of Implant Stability Following Sinus Lift: A Pilot Clinical Study.
AB  - AIM: The aim of this study was to evaluate the implant stability of Bredent Sky
      Blue implants of different diameters following one stage sinus lift procedure.
      MATERIAL AND METHODS: This study included 9 male patients with an existing
      indication for unilateral or bilateral sinus lift procedure. As grafting
      materials, combination of allograft material MinerOss(r) cortical & cancellous
      and Ossceram nano were used. RESULTS: All implants were considered successful and
      ISQ levels were measured by Osstell ISQ device. The ISQ values were from 68 to
      84. The mean values of stability of Bredent Sky Blue implants of different
      diameters following one stage sinus lift procedure were 77.73 +/- 2.93 (MD) and
      77.98 +/- 2.72 (VO).

PMID- 27688408
TI  - Quorum Sensing of Periodontal Pathogens.
AB  - The term 'quorum sensing' describes intercellular bacterial communication which
      regulates bacterial gene expression according to population cell density.
      Bacteria produce and secrete small molecules, named autoinducers, into the
      intercellular space. The concentration of these molecules increases as a function
      of population cell density. Once the concentration of the stimulatory threshold
      is reached, alteration in gene expression occurs. Gram-positive and Gram-negative
      bacteria possess different types of quorum sensing systems. Canonical LuxI/R
      type/acyl homoserine lactone mediated quorum sensing system is the best studied
      quorum sensing circuit and is described in Gram-negative bacteria which employ it
      for inter-species communication mostly. Gram-positive bacteria possess a peptide
      mediated quorum sensing system. Bacteria can communicate within their own species
      (intra-species) but also between species (inter-species), for which they employ
      an autoinducer-2 quorum sensing system which is called the universal language of
      the bacteria. Periodontal pathogenic bacteria possess AI-2 quorum sensing
      systems. It is known that they use it for regulation of biofilm formation, iron
      uptake, stress response and virulence factor expression. A better understanding
      of bacterial communication mechanisms will allow the targeting of quorum sensing
      with quorum sensing inhibitors to prevent and control disease. 

PMID- 27688410
TI  - Influence of Adhesives and Methods of Enamel Pretreatment on the Shear Bond
      Strength of Orthodontic Brackets.
AB  - AIM: The objective of present study was to examine influence of adhesives and
      methods of enamel pretreatment on the shear bond strength (SBS) of orthodontic
      brackets. The adhesives used were resin-reinforced glass ionomer cements-GIC
      (Fuji Ortho LC) and composite resin (Transbond XT). MATERIAL AND METHODS: The
      experimental sample consisted of 80 extracted human first premolars. The sample
      was divided into four equal groups, and the metal brackets were bonded with
      different enamel pretreatments by using two adhesives: group A-10% polyacrylic
      acid; Fuji Ortho LC, group B-37% phosphoric acid; Fuji Ortho LC, group C-self
      etching primer; Transbond XT, group D-37% phosphoric acid, primer; Transbond XT.
      SBS of brackets was measured. After debonding of brackets, the adhesive remnant
      index (ARI) was evaluated. RESULTS: After the statistical analysis of the
      collected data was performed (ANOVA; Sheffe post-hoc test), the results showed
      that significantly lower SBS of the group B was found in relation to the groups C
      (p=0.031) and D (p=0.026). The results of ARI were similar in all testing groups
      and it was not possible to determine any statistically significant difference of
      the ARI (Chi- square test) between all four experimental groups. CONCLUSION: The
      conclusion is that the use of composite resins material with appropriate enamel
      pretreatment according to manufacturer's recommendation is the "gold standard"
      for brackets bonding for fixed orthodontic appliances.

PMID- 27688409
TI  - The Effect of Microwave Disinfection on Denture Base Polymers, Liners and Teeth:
      A Basic Overview.
AB  - The aim of this paper was to overview the current scientific knowledge concerning
      the effect of microwave disinfection on denture related material properties.
      Cross-infection control in dentistry is a significant issue in everyday clinical
      practice due to the recent increase in some infectious diseases such as hepatitis
      B, C and AIDS and therefore numerous methods of disinfection have been used. The
      most widespread method of disinfection used in everyday practice is chemical,
      however, studies have suggested that chemical disinfectants alter the physical
      and mechanical properties of the acrylic resins and enable the growth and
      proliferation of certain bacteria. Therefore, microwaves were introduced as an
      easy to use-and-access, low cost, chemical free alternative. The question that
      arose was if and in what way the microwave irradiation affected the denture
      related material properties. Microwaving affects the denture resin bases, liners
      and teeth in different ways. The results showed that microwave disinfection could
      be a safe alternative for the disinfection of denture bases and liners compared
      to the chemical one, when the procedure is carried out in dry conditions, but
      could possibly cause dimensional changes of clinical significance on them when
      the irradiation takes place in wet environment. It also seems to have no
      detrimental effects of clinical importance on the flexural properties, impact
      strength and hardness of denture resins and the bond, flexural strength, porosity
      and hardness of denture liners. The effects of microwave disinfection on the
      hardness of denture teeth and teeth/denture bond strength are still controversial
      and no safe conclusions can be drawn. 

PMID- 27688411
TI  - Presentation of DMFT/dmft Index in Croatia and Europe.
AB  - BACKGROUND: Dental caries is the most common oral disease affecting all age
      groups and a major cause of tooth loss. Although a decrease in the prevalence of
      dental caries has been marked across the globe, in many countries it has remained
      a major oral-health problem. AIM: The objective of this paper was to show the
      trends in the DMFT/dmft index in Croatia, compare it with European countries and
      present further courses of action oriented towards promotion of oral health and
      decrease in caries prevalence. MATERIAL AND METHODS: The DMFT index databases
      have been generated based on online database searches for the period from 1985 to
      2015. RESULTS: Croatia is one of European countries with a high DMFT index
      relating to 12-year old children (4.18). The experience of countries with a low
      DMFT index has shown that dental caries can be controlled through education and
      prevention activities, which eventually lead to diminished financial costs, at
      individual and national level, improving overall health and quality of life.
      CONCLUSION: Tracking and monitoring of oral health i.e. dental caries need to be
      improved in terms of creation of data base systems on the prevalence of dental
      caries, determining multi-factorial causes of its occurrence and with respect to
      the implementation of national oral-health prevention programs.

PMID- 27688412
TI  - A Comparative Study of Shaping Ability of four Rotary Systems.
AB  - PURPOSE: This study compared the cutting area, instrumentation time, root canal
      anatomy preservation and non-instrumented areas obtained by F360((r)), Mtwo((r)),
      RaCe((r)) and Hyflex((r)) files with ISO size 35. MATERIAL AND METHODS: 120 teeth
      with a single straight root and root canal were divided into 4 groups. Working
      length was calculated by using X-rays. The teeth were sectioned with a handpiece
      and a diamond disc, and the sections were observed with Nikon SMZ-2T stereoscopic
      microscope and an Intralux 4000-1 light source. The groups were adjusted with a
      preoperative analysis with AutoCAD. The teeth were reconstructed by a #10 K-File
      and epoxy glue. Each group was instrumented with one of the four file systems.
      The instrumentation time was calculated with a 1/100 second chronometer. The area
      of the thirds and root canal anatomy preservation were analyzed with AutoCAD 2013
      and the non-instrumented areas with AutoCAD 2013 and SMZ-2T stereoscopic
      microscope. The statistical analysis was made with Levene's Test, ANOVA,
      Bonferroni Test and Pearson's Chi-square. RESULTS: Equal variances were shown by
      Levene's Test (P > 0.05). ANOVA (P > 0.05) showed the absence of significant
      differences. There were significant differences in the instrumentation time (P <
      0.05). For root canal anatomy preservation and non-instrumented areas, there were
      no significant differences between all systems (P > 0.05). CONCLUSIONS: The 4
      different rotary systems produced similar cutting area, root canal anatomy
      preservation and non-instrumented areas. Regarding instrumentation time,
      F360((r)) was the fastest system statistically.

PMID- 27688414
TI  - Four year Evaluation of Proximal Resin Infiltration in Adolescents.
AB  - AIM: Resin infiltration of proximal lesions is a new approach to stopping caries
      progression. Therefore, the aim of the present study was to evaluate four-year
      efficacy of proximal infiltrates in adolescents. MATERIALS AND METHODS: In ten
      adolescents, a total of 21 proximal infiltrates (ICON(r) (DMG, Germany) were
      applied to initial proximal lesions of permanent incisors and premolars according
      to the manufacturer's instruction. The clinical quality of resin infiltration was
      assessed at 1 week, 1, 2, 3 and 4 years after the treatment and the evaluation of
      the therapeutic effect was analyzed by radiographs. RESULTS: Ten patients were
      followed up clinically for four years. The majority of the infiltrated lesions
      were located on permanent incisors. Teeth which were proximally infiltrated did
      not exhibit dental plaque and gingival bleeding in most cases. At annual recalls,
      plaque scores remained constant. The gingival status remained steady and no
      differences in tooth shape and contour were detected. Discoloration was detected
      in four teeth (19%) in 1st year recall and was constant at annual intervals. The
      radiographic evaluation of the bitewing radiographs showed no progression in 21
      lesions (100%) from baseline to the 4-year recall. Overall oral hygiene of the
      patients was satisfactory. CONCLUSION: In conclusion, proximal infiltration is an
      effective prophylactic measure in adolescents.

PMID- 27688413
TI  - Evaluation of Microbial Reduction in Root Canals Instrumented with Reciprocating
      and Rotary Systems.
AB  - OBJECTIVE: This in vitro study aimed to evaluate the efficacy of the disinfection
      of root canal systems carried out with Reciproc(TM) and ProTaper Universal(TM)
      systems using 1% sodium hypochlorite (NaOCl). METHODS: Forty human single-rooted
      mandibular premolars were infected with Enterococcus faecalis, Pseudomonas
      aeruginosa, Staphylococcus aureus and Candida albicans, and twenty were not
      infected. The specimens were randomly divided into 6 groups (n = 10): Group 1:
      ProTaper Universal(TM) + 1% NaOCl; Group 2 (positive control): ProTaper
      Universal(TM) + saline; Group 3 (negative control without microorganisms):
      ProTaper Universal(TM) + saline; Group 4: Reciproc(TM) + 1% NaOCl; Group 5
      (positive control): Reciproc(TM) + saline; Group 6 (negative control without
      microorganisms): Reciproc(TM) + saline. Samples were collected before and after
      the completion of specific treatments, and plated in specific media cultures. The
      Fisher exact test was used for the statistical analysis of differences in terms
      of presence or absence of microbial growth among groups. For all tested
      pathogens, significant differences (p < 0.001) were verified between the
      instrumentation systems used. RESULTS: ProTaper Universal(TM) associated with 1%
      NaOCl completely eliminated all microorganisms. Microbial growth, however, was
      observed when Reciproc(TM) was used associated with 1% NaOCl. CONCLUSION:
      According to the protocol executed for this study, the Reciproc(TM) system
      associated with 1% NaOCl was not able to completely eliminate E. faecalis, P.
      aeruginosa, S. aureus and C. albicans from the root canal systems.

PMID- 27688415
TI  - The Effect of Tobacco Smoking on Salivation.
AB  - AIM: The purpose of this study was to examine the detrimental effect of smoking
      on the function of the salivary glands. MATERIAL AND METHODS: The study was
      conducted on 60 patients who were divided into two groups: a test group which
      included smokers and control group represented by non-smokers. Each group
      included 30 patients. General information was collected from all the respondents
      via a questionnaire as well as the data on the duration of smoking and number of
      cigarettes smoked per day. Saliva was collected by spitting method in a graduated
      tube and the amount of unstimulated and stimulated saliva was measured and
      recorded in ml per minute. Stimulated saliva was collected immediately after
      rinsing the mouth with a 2% aqueous solution of citric acid which is carried
      salivary stimulation. The presence of pigmentation on the teeth and coated tongue
      were recorded during clinical examination. The degree of oral hygiene was
      determined by plaque index. All the obtained data were statistically analyzed
      with significance level p <0.05. RESULTS: The results showed no significant
      differences in the amount of saliva between smokers and non-smokers, however, the
      amount of saliva decreases significantly with the duration of smoking and
      increasing age of smokers. Also proven was the difference in the quality of
      saliva: smokers have thick saliva and nonsmokers predominantly serous. In
      addition, smokers have poorer oral hygiene status than non-smokers, and
      demonstrated a positive correlation between the level of oral hygiene and length
      of smoking tobacco. CONCLUSION: This study has proven that smoking adversely
      affects salivation: long-term smoking reduces the secretion of saliva and changes
      its quality.

PMID- 27688416
TI  - Flexible Removable Partial Denture Prosthesis: A Survey of Dentists' Attitudes
      and Knowledge in Greece and Croatia.
AB  - PURPOSE: The aim of this study was to investigate through a questionnaire the
      knowledge, attitudes and possible differences in the use of flexible RPDPs among
      dentists in Greece and Croatia. MATERIAL AND METHODS: A questionnaire of 16
      questions was originally created in English, translated into Greek and Croatian
      language following a two way translation and tested for apprehension, precision,
      clarity and homogeneity by a number of native English speaking Greek and Croatian
      dentists. Following the necessary corrections, the questionnaires replicated in
      two online surveys and their addresses with an informed consent were sent by
      emails to nearly 4000 dentists in each country to participate. Collected data
      were analyzed by chi-square tests at a= .05 level of significance. RESULTS: 378
      dentists from Greece and 304 from Croatia participated in the study. 137(36.2%)
      dentists from Greece and 56(18.4%) from Croatia provided flexible RPDPs to their
      patients. Statistical analysis for all providers indicated no significant
      difference between genders (P>.05), significant differences between age groups
      (P<.01), years of practice (P<.05), specialization (P <.001), and instruction on
      flexible prostheses (P <.001). The analysis between the two countries showed
      differences for gender and age groups (P<.01) but no differences between
      experienced, specialized or instructed groups (P >.05). CONCLUSION: The survey
      indicated differences between the two countries in the percentages of dentists
      using, selecting and providing RPDPs for their patients. Practitioners' age,
      years in practice and instruction were associated with the provision of the
      prostheses, while comfort, esthetics and cost were the reasons for deciding to
      use the flexible RPDPs. CONCLUSION: Although dentists are not educated in their
      schools about flexible RPDPs, almost a third of them offer this treatment to
      their patients. Long term success of these devices depends on clinical education,
      more experience and definitely more research.

PMID- 27688417
TI  - The Influence of Different Nonsteroidal Anti-Inflammatory Drugs on Alveolar Bone
      in Rats: An Experimental Study.
AB  - THE AIM: The aim of this study was to investigate the effect of dexketoprofen
      trometamol, meloxicam, diclofenac sodium on any untreated alveolar bone when they
      are used as drugs for another indication. MATERIALS AND METHODS: Twenty eight
      male Spraque-Dawley rats were randomized into four groups as dexketoprofen
      trometamol (Group I), meloxicam (Group II), diclofenac sodium (Group III) and
      control group. Nonsteroidal anti-inflammatory drugs (NSAID) were administered
      after a fibula fracture for 10 days. Untreated alveolar bone was
      histopathologically examined for spongious bone density, osteoclastic density and
      osteoblastic density. RESULTS: Spongious bone density was lower in study groups
      (Group I, group II and group III) than the control group (p<0.05). In contrast,
      the increase in osteoclastic density was observed in other groups apart from the
      control group (p<0.05). Osteoblastic density was evaluated and it was determined
      that group II and group III had lower results than the control group (p<0.05) but
      group I was equal to the control group. CONCLUSION: This study showed that
      systemically administrated NSAIDs have the potential to affect untreated alveolar
      bone. This should also be considered in long term use of NSAIDs.

PMID- 27688418
TI  - Mapping Electrical Impedance Spectra of the Healthy Oral Mucosa: a Pilot Study.
AB  - OBJECTIVE: Electrical impedance is the resistance to the electric current flow
      through a tissue and depends on the tissue's structure and chemical composition.
      The aim of this study was to map electrical impedance spectra for each region of
      the healthy oral mucosa. MATERIALS AND METHODS: Electrical impedance was measured
      in 30 participants with healthy oral mucosa. Measurements were performed in 14
      points on the right and the left side of the oral cavity, and repeated after 7
      and 14 days respectively. RESULTS: The lowest values were measured on the tongue
      dorsum and the highest values were measured on the hard palate. No significant
      differences were found between the right and the left side. Significantly higher
      values were found in females on the upper labial mucosa, tongue dorsum and the
      ventral tongue. Significant difference between smokers and non-smokers on the
      lower labial mucosa and floor of the mouth was found. Electrical impedance was
      negatively correlated with salivary flow on the upper labial mucosa, hard palate,
      tongue dorsum and sublingual mucosa. Higher variability of measurements was found
      at low frequencies. CONCLUSIONS: Electrical impedance mostly depends on the
      degree of mucosal keratinization. Demographic and clinical factors probably
      affect its values. Further studies with bigger number of participants are
      required.

PMID- 27688420
TI  - 50th Anniversary of Acta stomatologica Croatica.
AB  - Acta stomatologica Croatisa (ASCRO) is scientific-professional magazine whose
      first issue was published back in 1966. Ever since the magazine publishers were
      the School of Dental Medicine of the University of Zagreb and the Croatian Dental
      Association of the Croatian Medical Association. Over the past fifty years two
      hundred regular editions were pubslihed along with three additions. The magazine
      has been internationally indexed and it was granted the DOI number. In this way
      by means of CrossCheck possible plagiarisms are being checked which aims at
      obtaining originality of the published results. Another peculiarity of ASCRO is
      bilingualism throughout the whole edition, international recognizability, open
      source and tradition based on sound foundations. 

PMID- 27688419
TI  - Assessment of Oro-Maxillofacial Trauma According to Gender, Age, Cause and Type
      of the Injury.
AB  - OBJECTIVES: The occurrence and causes of maxillofacial trauma varies in different
      regions of the world. The aim of this study was to identify the occurrence, types
      and causes of maxillofacial injuries according to the age and gender differences
      in patients treated at the Department of Maxillofacial Surgery, University
      Hospital Center Osijek, between January 2011 and December 2013. MATERIALS AND
      METHODS: A total of 64 patients, 41 males (64.1%) and 23 females (35.9%), aged
      from 18 to 86 years (mean age 42) participated in the study. Data collected and
      analyzed included gender, age, cause of injury and the type of maxillofacial
      injuries. RESULTS: The most common cause of injuries in both gender groups was
      falling down (39% males; 65% females). The second leading cause of injuries in
      males was interpersonal violence (29%) and in females traffic accident (26%)
      (p<0.05). The most common type of injury in both gender groups was bone injury
      (50%; in males zygomatic bones 55%, in females mandible 40%) (p>0.05). The most
      common causes of injuries in the youngest patients was violence (43%), and in
      others fall (50-70%; p<0.05). The most common reported type of injury in all age
      groups was bone injury (more than 50%; p>0.05). The majority of the falls and
      violence caused bone tissue injuries, and soft tissue and dentalveolar injuries
      were detected in traffic and sports accidents (p>0.05). CONCLUSION: Falling down
      was the most common cause of oro-maxillofacial injuries in both men and women and
      in all three age groups. The leading type of injury was bone injury. The data
      obtained from this study provide important information for future prevention from
      injuries.

PMID- 27688421
TI  - Cytotoxicity of Two Bioactive Root Canal Sealers.
AB  - OBJECTIVE: The aim of this study was to investigate the cytotoxicity of two
      different bioactive root canal sealers: one based on mineral trioxide aggregate,
      MTA Fillapex (Angelus, Solucoes Odontologicas, Londrina, PR, Brazil), and the
      other based on bioceramics, Endosequence BC Sealer (Brasseler, Savannah, Georgia,
      USA), in culture of mouse L929 fibroblasts. MATERIALS AND METHODS: Mouse
      fibroblasts (L929), obtained from subcutaneous connective tissue of mouse line
      C3Hf, were cultivated in plastic culture flasks in an incubator at 37sC, with 5%
      CO2 and 90% humidity. Freshly mixed Endosequence BC Sealer and MTA Fillapex (0.1
      g each) were placed on sterile teflon discs, 6 mm in diameter. Teflon discs with
      the materials as well as empty discs serving as control were placed in wells of
      12-well plate. After incubation times of 1, 6, 20 and 24 hours, the teflon discs
      were removed from the wells and the number of viable cells was determined using
      trypan blue in Neubauer chamber. RESULTS: In comparison to the control group, MTA
      Fillapex had significantly less viable cells for all incubation periods
      (p<=0.05), while Endosequence BC sealer had significantly less viable cells after
      6, 20, and 24 hours of incubation (p<=0.05). MTA Fillapex comprised significantly
      less viable cells in comparison to Endosequence BC sealer after the first hour
      and after 20 hours of incubation (p<=0.05), while for the other incubation
      periods there were no significant differences (p>=0.05). CONCLUSION: MTA Fillapex
      and Endosequence BC sealer were both cytotoxic in cultures of mouse L929
      fibroblasts.

PMID- 27688422
TI  - Eradication of Intracanal Enterococcus Faecalis Biofilm by Passive Ultrasonic
      Irrigation and RinsEndo System.
AB  - AIM: The aim of the study was to compare the antimicrobial efficacy of three
      irrigation techniques after the use of standardized volume of NaOCl and with
      standardized time and irrigation. METHODOLOGY: Forty-eight single rooted teeth
      were inoculated with an Enterococcus faecalis suspension for 24 h. The remaining
      six canals served as negative controls. The 36 root canals were randomly
      distributed into three experimental groups; group 1, conventional syringe
      irrigation; group 2, automated-dynamic irrigation (RinsEndo); group 3, passive
      ultrasonic irrigation (PUI). In the first protocol, the standardized volume of 3%
      NaOCl (20 mL) was used and in the second protocol, and standardized irrigation
      time (45 seconds) was used. Samples from root canals were cultured and the colony
      forming units (CFUs) were counted. RESULTS: When the volume of the irrigant was
      standardized, RinsEndo was more effective than PUI (p<0.01). When the irrigation
      time was standardized, there were no significant differences between any
      irrigation techniques (p>0.05). The RinsEndo group had the highest percentage of
      minimal counts of E. faecalis CFUs. CONCLUSIONS: RinsEndo was more effective than
      PUI only when the volume of the irrigant was standardized. However, the RinsEndo
      provided higher bacterial reduction in both protocols when using the least amount
      of the irrigant and providing longer contact time.

PMID- 27688423
TI  - Evaluation of Periodontal Parameters in Patients with Early Stage Chronic
      Lymphocytic Leukemia.
AB  - OBJECTIVE: To assess periodontal conditions in patients with early stage CLL and
      to compare it with the periodontal status of age matched healthy controls and to
      analyze the relationship between periodontal and hematological parameters in CLL
      patients. MATERIALS AND METHODS: 60 subjects were examined: 30 patients with CLL
      Rai 0 (test group) and 30 age-matching healthy individuals (control group). The
      exclusion criteria were: presence of other systemic disease or condition (e.g.
      diabetes), history of treatment for periodontitis, use of antibiotics during the
      last 3 months, use of medications. Socio-demographic data were obtained by means
      of a questionnaire. Participants with at least 8 teeth underwent a full mouth
      examination assessing API, PBI, PPD, REC and CAL. Medical data for CLL patients
      were collected from the patients' records, while hematological data were obtained
      from the hemogram. RESULTS: Difference between groups was statistically
      significant for age, number of teeth and frequency of dental checkups (p<0.05).
      Patients with CLL had significantly higher average values of periodontal indices
      (API 0.81+/-0.18; PBI 2.72+/-0.68; PPD 3.40+/-0.53; REC 1.95+/-0.87, CAL 4.37+/
      0.80) compared to the control group (API 0.69+/-0.15; PBI 1.91+/-0.45; PPD 2.51+/
      0.40; REC 0.99+/-0.54; CAL 3.00+/-0.58). The correlation coefficients between age
      and periodontal indices showed statistically significance between age and REC
      (r=0.357; p<0.01), and age and CAL (r=0.295; p<0.05). Age was not statistically
      significant covariate for CAL (F=2.205; p>0.05), only for REC (F=4.601; p<0.05).
      After the removal of the statistical effect of age, the difference in REC between
      CLL and control group remained statistically significant (F=19.732; p<0.01;
      eta(2)=0.287). Statistically significant association between periodontal and
      hematological parameters in CLL patients was not found (p>0.05). CONCLUSION: The
      results of this study showed that patients with CLL had worse periodontal status
      compared to healthy subjects. Causal relationship between periodontal and
      hematological parameters was not proved.

PMID- 27688424
TI  - In Vivo Evaluations of Inter-Observer Reliability Using VITA Easyshade(r) Advance
      4.0 Dental Shade-Matching Device.
AB  - OBJECTIVES: The aim of this study was to evaluate the inter-observer reliability
      of dental shade-matching device using an in vivo model. MATERIALS AND METHODS:
      Four observers who were well trained in color assessment and handling of the
      dental shade-matching device determined teeth color and CIE-Lab values on
      maxillary right central incisors in 10 patients with completely healthy and
      intact dentitions. VITA Easyshade(r) Advance 4.0 shade-matching device was
      utilized to measure the central region of the labial surface of all investigated
      teeth, twice by each observer. The inter-observer reliability of the measurements
      was observed and deviations between Lab and [Formula: see text]E values between
      the observers were calculated. Intraclass correlation coefficients (ICCs) were
      used to analyze inter-observer reliability. RESULTS: One-way ANOVA showed no
      statistically significant differences in color measurement of four observers in
      all the measured values (p>0.05). Delta E values ranged from 3.018 to 5.234.
      Although some small differences existed, statistically significant differences
      between the observers were not found (p>0.05). Inter-observer ICCs were very high
      for all observers (from 0.651 to 0.992). CONCLUSION: Inter-examiner reliability
      of measurements using VITA Easyshade(r) Advance 4.0 shade-matching device was
      acceptable. Apart from the digital equipment, a well trained observer seems to be
      crucial in order to achieve correct dental color measurement.

PMID- 27688425
TI  - Titanium Ions Release from an Innovative Titanium-Magnesium Composite: an in
      Vitro Study.
AB  - BACKGROUND: The innovative titanium-magnesium composite (Ti-Mg) was produced by
      powder metallurgy (P/M) method and is characterized in terms of corrosion
      behavior. MATERIAL AND METHODS: Two groups of experimental material, 1 mass% (Ti
      1Mg) and 2 mass% (Ti-2Mg) of magnesium in titanium matrix, were tested and
      compared to commercially pure titanium (CP Ti). Immersion test and chemical
      analysis of four solutions: artificial saliva; artificial saliva pH 4; artificial
      saliva with fluoride and Hank balanced salt solution were performed after 42 days
      of immersion, using inductively coupled plasma mass spectrometry (ICP-MS) to
      detect the amount of released titanium ions (Ti). SEM and EDS analysis were used
      for surface characterization. RESULTS: The difference between the results from
      different test solutions was assessed by ANOVA and Newman-Keuls test at p<0.05.
      The influence of predictor variables was found by multiple regression analysis.
      The results of the present study revealed a low corrosion rate of titanium from
      the experimental Ti-Mg group. Up to 46 and 23 times lower dissolution of Ti from
      Ti-1Mg and Ti-2Mg, respectively was observed compared to the control group. Among
      the tested solutions, artificial saliva with fluorides exhibited the highest
      corrosion effect on all specimens tested. SEM micrographs showed preserved dual
      phase surface structure and EDS analysis suggested a favorable surface
      bioactivity. CONCLUSION: In conclusion, Ti-Mg produced by P/M as a material with
      better corrosion properties when compared to CP Ti is suggested.

PMID- 27688426
TI  - Education on occupational health and health related habits among dental students
      in Croatia.
AB  - INTRODUCTION: Occupational diseases are diseases caused by occupational exposures
      at the workplace, while diseases related to work are diseases caused by many
      factors, wherein the harmful work conditions are one of the possible causes.
      Dental medicine is a profession with a high risk of developing occupational
      diseases. The aim of this paper was to present the results of a survey about
      occupational health risks and health related habits among dental students at the
      School of Dental Medicine University of Zagreb and to show how this survey led to
      an improvement in education by introducing a new course into the dental
      curriculum. PARTICIPANTS AND METHODS: Students of all years at the School of
      Dental Medicine University of Zagreb (total of 663) were offered to participate
      in a survey about occupational health risks and health related habits. RESULTS: A
      questionnaire was completed by 351 students. 28.0% of male students and 22.5% of
      female students were smokers. During the first two years of study, up to 84.6% of
      students consumed alcoholic beverages at least once a week. Prior to enrollment
      in the university, 85.3% male and 77.6% female students were engaged in sports.
      The significant drop in the number of students who participated in sports was
      noticed in the first study year in both sexes. Student awareness of the health
      risks related to dental profession increases with the year of study. Most
      students believe that occupational diseases can be prevented. CONCLUSION: The
      results have shown that students enter the School of Dental Medicine with a
      relatively low level of awareness of the health hazards of dental profession.
      Although the level of awareness increases with years of study, harmful habits
      such as smoking, alcohol consumption, and the lack of physical activity also
      remain present in the later years of study.

PMID- 27688427
TI  - Prevalence and Pattern of Non-Syndromic Hypodontia in a Group of Turkish
      Children.
AB  - OBJECTIVE: The aim of this study was to assess the prevalence and pattern of
      congenital missing teeth in the permanent dentition (excluding wisdom teeth),
      among Turkish children in a 4-year period (2009-2012). METHODS: The study group
      comprised 1658 children (873 girls, 785 boys). The children were examined in
      Department of Pediatric Dentistry, Dental School of Marmara University. A chi
      square test was used to determine the difference in the prevalence of hypodontia
      between genders. RESULTS: The prevalence of hypodontia was 6.2% (6.3% girls, 6%
      boys) with no statistically significant difference between the genders (P=0.601).
      The most frequently missing tooth were the mandibular left second premolars, 63
      (20.7%), followed by the mandibular right second premolars, 61(20.1%), maxillary
      left premolars, 31 (10.2%). There were 89 anterior and 214 posterior missing
      teeth. Bilateral hypodontia was observed in 70 (39 girls, 31 boys) patients
      (67.9%). The most common bilateral missing teeth were the mandibular second
      premolar (22 girls, 21 boys) (42.1%) and the maxillary second premolar (6 girls,
      15 boys) (20.5%). The mandibular left second premolar (9 boys, 8 girls) was the
      most frequent unilaterally missing tooth (5.6%) followed by the mandibular right
      second premolar (10 girls, 6 boys) (5.28%). CONCLUSION: The obtained results
      point to the importance of detailed clinical and radiographic examination. These
      help with long-term treatment planning according to a child's individual
      requirements.

PMID- 27688428
TI  - Developmental Defects of Enamel in Children with Intellectual Disability.
AB  - OBJECTIVES: To investigate the frequency of developmental defects of enamel (DDE)
      in children with intellectual disability. SUBJECTS AND METHODS: Children aged 5
      18 years (72 children with intellectual disabilities and 72 controls) were
      included in the study. All the teeth were screened for developmental defects of
      enamel using the modified Developmental defects of enamel (mDDE) index. RESULTS:
      Out of the 72 children with intellectual disabilities in this study, 20 (27.78%)
      presented dental defects of enamel, compared with 8 (11.11%) of those in the
      control group, which was considered statistically significant (p = 0.021). The
      majority of children in both groups had white demarcated opacities. Children in
      both groups were more likely to have maxillary teeth affected than the mandibular
      teeth and the asymmetrical demarcated enamel defects were more common than the
      symmetric ones. Majority of opacities in children in both groups were on the
      maxillary incisors. CONCLUSIONS: Children with intellectual disabilities have
      more developmental defects of enamel than children in the control group. Enamel
      defects increase caries risk and cause reduction in enamel mechanical properties
      leading to restoration failures.

PMID- 27688429
TI  - Medical Emergencies in Pediatric Dentistry.
AB  - Medical emergencies that are life threatening can occur in dental practice.
      Complications may arise because of an underlying disease or a reaction to
      medication. Reactions to medications may be allergic and toxic. The most common
      reactions are toxic reactions to local anesthetics, whereas allergies occur
      mainly as a consequence of the application of antibiotics, usually penicillin. In
      response to stress, vasovagal syncope typically occurs. Other causes may be
      related to an underlying disease-specific pathology (such as acute asthma attack,
      diabetic ketoacidosis, hypoglycemia, or seizures) or accidents (aspiration of a
      foreign body causing obstruction of the respiratory system). For all the above
      conditions, guidelines have been established that need to be known. If
      complications occur or necessary measures are not taken, it can lead to cardiac
      and respiratory arrest. Therefore, cardiopulmonary resuscitation is needed. All
      procedures and dosages should be adapted to the age of the child. 

PMID- 27688430
TI  - Farms, Families, and Markets: New Evidence on Completeness of Markets in
      Agricultural Settings.
AB  - The farm household model has played a central role in improving the understanding
      of small-scale agricultural households and non-farm enterprises. Under the
      assumptions that all current and future markets exist and that farmers treat all
      prices as given, the model simplifies households' simultaneous production and
      consumption decisions into a recursive form in which production can be treated as
      independent of preferences of household members. These assumptions, which are the
      foundation of a large literature in labor and development, have been tested and
      not rejected in several important studies including Benjamin (1992). Using
      multiple waves of longitudinal survey data from Central Java, Indonesia, this
      paper tests a key prediction of the recursive model: demand for farm labor is
      unrelated to the demographic composition of the farm household. The prediction is
      unambiguously rejected. The rejection cannot be explained by contamination due to
      unobserved heterogeneity that is fixed at the farm level, local area shocks or
      farm-specific shocks that affect changes in household composition and farm labor
      demand. We conclude that the recursive form of the farm household model is not
      consistent with the data. Developing empirically tractable models of farm
      households when markets are incomplete remains an important challenge.

PMID- 27688431
TI  - W' expenditure and reconstitution during severe intensity constant power
      exercise: mechanistic insight into the determinants of W'.
AB  - The sustainable duration of severe intensity exercise is well-predicted by
      critical power (CP) and the curvature constant (W'). The development of the W'BAL
      model allows for the pattern of W' expenditure and reconstitution to be
      characterized and this model has been applied to intermittent exercise protocols.
      The purpose of this investigation was to assess the influence of relaxation phase
      duration and exercise intensity on W' reconstitution during dynamic constant
      power severe intensity exercise. Six men (24.6 +/- 0.9 years, height: 173.5 +/-
      1.9 cm, body mass: 78.9 +/- 5.6 kg) performed severe intensity dynamic handgrip
      exercise to task failure using 50% and 20% duty cycles. The W'BAL model was fit
      to each exercise test and the time constant for W' reconstitution (tauW') was
      determined. The tauW' was significantly longer for the 50% duty cycle (1640 +/-
      262 sec) than the 20% duty cycle (863 +/- 84 sec, P = 0.02). Additionally, the
      relationship between tauW' and CP was well described as an exponential decay
      (r(2) = 0.90, P < 0.0001). In conclusion, the W'BAL model is able to characterize
      the expenditure and reconstitution of W' across the contraction-relaxation cycles
      comprising severe intensity constant power handgrip exercise. Moreover, the
      reconstitution of W' during constant power severe intensity exercise is
      influenced by the relative exercise intensity, the duration of relaxation between
      contractions, and CP.

PMID- 27688432
TI  - Leucine-rich repeat containing protein LRRC8A is essential for swelling-activated
      Cl- currents and embryonic development in zebrafish.
AB  - A volume-regulated anion channel (VRAC) has been electrophysiologically
      characterized in innumerable mammalian cell types. VRAC is activated by cell
      swelling and mediates the volume regulatory efflux of Cl(-) and small organic
      solutes from cells. Two groups recently identified the mammalian leucine-rich
      repeat containing protein LRRC8A as an essential VRAC component. LRRC8A must be
      coexpressed with at least one of the other four members of this gene family,
      LRRC8B-E, to reconstitute VRAC activity in LRRC8(-/-) cells. LRRC8 genes likely
      arose with the origin of chordates. We identified LRRC8A and LRRC8C-E orthologs
      in the zebrafish genome and demonstrate that zebrafish embryo cells and
      differentiated adult cell types express a swelling-activated Cl(-) current
      indistinguishable from mammalian VRAC currents. Embryo cell VRAC currents are
      virtually eliminated by morpholino knockdown of the zebrafish LRRC8A ortholog
      lrrc8aa VRAC activity is fully reconstituted in LRRC8(-/-) human cells by
      coexpression of zebrafish lrrc8aa and human LRRC8C cDNAs. lrrc8aa expression
      varies during zebrafish embryogenesis and lrrc8aa knockdown causes pericardial
      edema and defects in trunk elongation and somatogenesis. Our studies provide
      confirmation of the importance of LRRC8A in VRAC activity and establish the
      zebrafish as a model system for characterizing the molecular regulation and
      physiological roles of VRAC and LRRC8 proteins.

PMID- 27688433
TI  - Contraction mode itself does not determine the level of mTORC1 activity in rat
      skeletal muscle.
AB  - Resistance training with eccentric contraction has been shown to augment muscle
      hypertrophy more than other contraction modes do (i.e., concentric and isometric
      contraction). However, the molecular mechanisms involved remain unclear. The
      purpose of this study was to investigate the effect of muscle contraction mode on
      mammalian target of rapamycin complex 1 (mTORC1) signaling using a standardized
      force-time integral (load (weight) * contraction time). Male Sprague-Dawley rats
      were randomly assigned to three groups: eccentric contraction, concentric
      contraction, and isometric contraction. The right gastrocnemius muscle was
      exercised via percutaneous electrical stimulation-induced maximal contraction. In
      experiment 1, different modes of muscle contraction were exerted using the same
      number of reps in all groups, while in experiment 2, muscle contractions were
      exerted using a standardized force-time integral. Muscle samples were obtained
      immediately and 3 h after exercise. Phosphorylation of molecules associated with
      mTORC1 activity was assessed using western blot analysis. In experiment 1, the
      force-time integral was significantly different among contraction modes with a
      higher force-time integral for eccentric contraction compared to that for other
      contraction modes (P < 0.05). In addition, the force-time integral was higher for
      concentric contraction compared to that for isometric contraction (P < 0.05).
      Similarly, p70S6K phosphorylation level was higher for eccentric contraction than
      for other modes of contraction (P < 0.05), and concentric contraction was higher
      than isometric contraction (P < 0.05) 3 h after exercise. In experiment 2, under
      the same force-time integral, p70S6K (Thr389) and 4E-BP1 phosphorylation levels
      were similar among contraction modes 3 h after exercise. Our results suggest that
      mTORC1 activity is not determined by differences in muscle contraction mode
      itself. Instead, mTORC1 activity is determined by differences in the force-time
      integral during muscle contraction.

PMID- 27688435
TI  - Lichen Planus Pigmentosus: The Controversial Consensus.
AB  - A pigmented variant of lichen planus (LP) was first reported from India in 1974
      by Bhutani et al. who coined the term LP pigmentosus (LPP) to give a descriptive
      nomenclature to it. LP has a number of variants, one of which is LPP. This
      disease has also later been reported from the Middle East, Latin America, Korea,
      and Japan, especially in people with darker skin. It has an insidious onset.
      Initially, small, black or brown macules appear on sun-exposed areas. They later
      merge to form large hyperpigmented patches. The disease principally affects the
      sun-exposed areas of the body such as the face, trunk, and upper extremities. The
      oral mucosa may rarely be involved. However, the palms, soles, and nails are not
      affected. Histologically, the epidermis is atrophic along with vacuolar
      degeneration of basal cell layer. The dermis exhibits incontinence of pigment
      with scattered melanophages and a sparse follicular or perivascular infiltrate.
      There is a considerable similarity in histopathological findings between LPP and
      erythema dyschromicum perstans. However, there are immunologic and clinical
      differences between the two. These observations have led to a controversy
      regarding the identity of the two entities. While some dermatologists consider
      them to be the same, others have opined that the two should be considered as
      distinctly different diseases. A number of associations such as hepatitis C virus
      infection, frontal fibrosing alopecia, acrokeratosis of Bazex and nephrotic
      syndrome have been reported with LPP. A rare variant, LPP inversus, with similar
      clinical and histopathological findings was reported in 2001. As opposed to LPP,
      this variant occurs in covered intertriginous locations such as groins and
      axillae and mostly affects white-skinned persons. 

PMID- 27688437
TI  - Biostatistics Series Module 5: Determining Sample Size.
AB  - Determining the appropriate sample size for a study, whatever be its type, is a
      fundamental aspect of biomedical research. An adequate sample ensures that the
      study will yield reliable information, regardless of whether the data ultimately
      suggests a clinically important difference between the interventions or elements
      being studied. The probability of Type 1 and Type 2 errors, the expected variance
      in the sample and the effect size are the essential determinants of sample size
      in interventional studies. Any method for deriving a conclusion from experimental
      data carries with it some risk of drawing a false conclusion. Two types of false
      conclusion may occur, called Type 1 and Type 2 errors, whose probabilities are
      denoted by the symbols sigma and beta. A Type 1 error occurs when one concludes
      that a difference exists between the groups being compared when, in reality, it
      does not. This is akin to a false positive result. A Type 2 error occurs when one
      concludes that difference does not exist when, in reality, a difference does
      exist, and it is equal to or larger than the effect size defined by the
      alternative to the null hypothesis. This may be viewed as a false negative
      result. When considering the risk of Type 2 error, it is more intuitive to think
      in terms of power of the study or (1 - beta). Power denotes the probability of
      detecting a difference when a difference does exist between the groups being
      compared. Smaller alpha or larger power will increase sample size. Conventional
      acceptable values for power and alpha are 80% or above and 5% or below,
      respectively, when calculating sample size. Increasing variance in the sample
      tends to increase the sample size required to achieve a given power level. The
      effect size is the smallest clinically important difference that is sought to be
      detected and, rather than statistical convention, is a matter of past experience
      and clinical judgment. Larger samples are required if smaller differences are to
      be detected. Although the principles are long known, historically, sample size
      determination has been difficult, because of relatively complex mathematical
      considerations and numerous different formulas. However, of late, there has been
      remarkable improvement in the availability, capability, and user-friendliness of
      power and sample size determination software. Many can execute routines for
      determination of sample size and power for a wide variety of research designs and
      statistical tests. With the drudgery of mathematical calculation gone,
      researchers must now concentrate on determining appropriate sample size and
      achieving these targets, so that study conclusions can be accepted as meaningful.

PMID- 27688438
TI  - Methodology Series Module 5: Sampling Strategies.
AB  - Once the research question and the research design have been finalised, it is
      important to select the appropriate sample for the study. The method by which the
      researcher selects the sample is the ' Sampling Method'. There are essentially
      two types of sampling methods: 1) probability sampling - based on chance events
      (such as random numbers, flipping a coin etc.); and 2) non-probability sampling -
      based on researcher's choice, population that accessible & available. Some of the
      non-probability sampling methods are: purposive sampling, convenience sampling,
      or quota sampling. Random sampling method (such as simple random sample or
      stratified random sample) is a form of probability sampling. It is important to
      understand the different sampling methods used in clinical studies and mention
      this method clearly in the manuscript. The researcher should not misrepresent the
      sampling method in the manuscript (such as using the term ' random sample' when
      the researcher has used convenience sample). The sampling method will depend on
      the research question. For instance, the researcher may want to understand an
      issue in greater detail for one particular population rather than worry about the
      ' generalizability' of these results. In such a scenario, the researcher may want
      to use ' purposive sampling' for the study. 

PMID- 27688434
TI  - Anti-inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in
      Dermatology.
AB  - Antibiotics (antibacterial, antiviral, and antiparasitic) are class of drugs
      which result in either killing or inhibiting growth and multiplication of
      infectious organisms. Antibiotics are commonly prescribed by all specialties for
      treatment of infections. However, antibiotics have hitherto immunomodulatory and
      anti-inflammatory properties and can be exploited for various noninfectious
      dermatoses. Dermatologists routinely prescribe antibiotics in treatment of
      various noninfectious disorders. This study will review anti-inflammatory and
      immunomodulatory effects of antibiotics and their use in dermatology. 

PMID- 27688439
TI  - Significance of Anti-cyclic Citrullinated Peptide Autoantibodies in Immune
      mediated Inflammatory Skin Disorders with and without Arthritis.
AB  - BACKGROUND: Anti-cyclic citrullinated peptides (CCPs) are autoantibodies directed
      against citrullinated peptides. Rheumatoid factor (RF), an antibody against the
      Fc portion of IgG, is known to form immune complexes and contribute to the
      etiopathogenesis of various skin disorders. C-reactive protein (CRP), an acute
      phase protein, increases following secretion of interleukin-6 from macrophages
      and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their
      diagnostic potential in immune-mediated skin disorders remains less widely
      studied. AIMS AND OBJECTIVES: To determine the correlation between anti-CCP, RF,
      and CRP in immune-mediated inflammatory skin diseases. MATERIALS AND METHODS:
      About 61 clinically diagnosed cases of various immune-mediated skin diseases
      (psoriasis [n = 38], connective tissue diseases such as systemic lupus
      erythematosus and systemic sclerosis [n = 14], and immunobullous disorders
      including pemphigus vulgaris and pemphigus foliaceus [n = 9]) were included in
      the study. These patients were subclassified on the basis of presence or absence
      of arthritis. Arthritis was present in nine cases of psoriasis and seven
      connective tissue disorder patients. Detection of serum anti-CCP was done using
      enzyme-linked immunosorbent assay, whereas CRP and RF levels were detected using
      latex agglutination technique. RESULTS: Of the 61 specimens, 14.75% had elevated
      serum anti-CCP levels. RF and CRP levels were elevated in 18.03% and 39.34%
      specimens, respectively. RF was elevated in 13.16% of inflammatory and 42.88% of
      connective tissue disorders, whereas anti-CCP was raised in 10.53% of
      inflammatory and 35.71% of connective tissue disorders. CRP positivity was
      highest in connective tissue disorders (50%), followed by 39.47% in inflammatory
      and 22.22% in immunobullous conditions. In none of the immunobullous patients,
      anti-CCP or RF levels were found to be elevated. Association of the presence of
      arthritis with elevated anti-CCP was found to be statistically significant.
      CONCLUSIONS: Although anti-CCP, RF, and CRP levels are valuable markers of
      chronic immune-mediated skin disorders, elaborate studies enrolling a larger
      number of patients are required to validate these diagnostic markers.

PMID- 27688440
TI  - The Psychosocial Impact of Acne Vulgaris.
AB  - BACKGROUND: Acne vulgaris causes erythematous papulopustular lesions in active
      stage and often leave behind residual scarring and pigmentation. Its onset in
      adolescence may add to the emotional and psychological challenges experienced
      during this period. AIMS: To assess the impact of acne on the various
      psychosocial domains of daily life. MATERIALS AND METHODS: This was a
      prospective, cross-sectional study done in the dermatology out-patient department
      of a tertiary care hospital from January to March 2015. A total of 100
      consecutive, newly diagnosed patients of acne vulgaris, aged 15 years and above
      were included in this study. The relationship between acne vulgaris and its
      sequelae was analyzed with ten different domains of daily life by using
      dermatology life quality index (DLQI) questionnaire. RESULTS: Females (56%), 15
      20 year olds (61%), facial lesions (60%), and Grade II acne (70%) were most
      common. Acne scars were noted in 75% patients, whereas 79% cases had post-acne
      hyperpigmentation. Thirty-seven percent patients had DLQI scores of (6-10)
      interpreted as moderate effect on patient's life. Statistically significant
      correlation (P < 0.05) found were as follows: Physical symptoms with grade of
      acne; embarrassment with site and grade of acne; daily activities with grade of
      acne and post-acne pigmentation; choice of clothes with site of acne; social
      activities with gender, site and grade of acne; effect on work/study with grade
      of acne; interpersonal problems with site and post-acne pigmentation; sexual
      difficulties with grade of acne. LIMITATION: It was a hospital-based study with
      small sample size. CONCLUSION: Significant impact of acne and its sequelae was
      noted on emotions, daily activities, social activities, study/work, and
      interpersonal relationships. Assurance and counseling along with early treatment
      of acne vulgaris is important to reduce disease-related psychosocial sequelae and
      increase the efficacy of treatment.

PMID- 27688436
TI  - Skin Hyperpigmentation in Indian Population: Insights and Best Practice.
AB  - Skin pigmentation is one of the most strikingly variable phenotypes in humans,
      therefore making cutaneous pigmentation disorders frequent symptoms manifesting
      in a multitude of forms. The most common among them include lentigines,
      postinflammatory hyperpigmentation, dark eye circles, and melasma. Variability of
      skin tones throughout the world is well-documented, some skin tones being
      reported as more susceptible to pigmentation disorders than others, especially in
      Asia and India. Furthermore, exposure to ultraviolet radiation is known to
      trigger or exacerbate pigmentation disorders. Preventive strategies for
      photoprotection and treatment modalities including topical and other medical
      approaches have been adopted by dermatologists to mitigate these disorders. This
      review article outlines the current knowledge on pigmentation disorders including
      pathophysiology, molecular profiling, and therapeutic options with a special
      focus on the Indian population. 

PMID- 27688441
TI  - Cutaneous Leishmaniasis in a Nonendemic Area of South Rajasthan: A Prospective
      Study.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) usually occurs in areas with hot and dry
      climate. In India, the desert areas of Rajasthan, Gujarat, and the plains of
      Northwestern frontier are endemic for this disorder. AIMS AND OBJECTIVES: The
      present study was aimed to describe clinicoepidemiological profile of the cases
      of CL from South Rajasthan, which is a nonendemic area of Rajasthan. MATERIALS
      AND METHODS: During a period of 4 years (2010-2014), a total of 23 patients with
      CL were diagnosed. All the suspected cases of CL were interrogated in detail
      regarding visit to areas where CL is known to occur. This was followed by
      clinical examination, relevant investigations, and treatment. All except one
      patient were treated with azole antifungals. In one patient, CO2 laser ablation
      was done. RESULTS: There were 12 (52.17%) males and 11 (47.83%) females with age
      ranging from 3 to 72 years. Duration of disease ranged from 7 days to 10 months.
      Face (15; 65.22%) and extremities (12; 52.17%) were involved in majority of the
      patients. Common morphologies were noduloulcerative lesions and crusted plaques.
      Tissue smear for Leishmania donovani bodies was positive in all except one
      patient. CONCLUSION: The present report highlights occurrence of CL in nonendemic
      area. Further epidemiological studies are required for identification of vector
      and strain of Leishmania involved.

PMID- 27688442
TI  - Dermatoses among Children from Celebration of "Holi," the Spring Festival, in
      India: A Cross-sectional Observational Study.
AB  - BACKGROUND: "Holi" is a spring festival celebrated primarily in the Indian
      subcontinent and also abroad by expatriate Indians. It is a festival of colors,
      traditionally celebrated by mutual application of colors in different forms on a
      particular day of the year. These colors frequently comprise a range of synthetic
      dyes which have harmful effects on the skin and mucosae. Children take part in
      this colorful festival with much enthusiasm and vigor, making them prone to
      develop different "Holi"-related dermatoses. Our objective was to find out the
      different patterns of "Holi"-related dermatoses in a group of pediatric patients.
      METHODOLOGY: This was a cross-sectional descriptive study carried out over a
      period of 6 years (2010-2015). Consecutive patients of pediatric age group who
      attended dermatology outpatient department (OPD) with different dermatoses
      following application of "Holi" color were included in this study. RESULTS: A
      total of 63 patients (mean age 11 years; range 1-16 years) were evaluated with a
      female to male ratio of 1.3:1. Itching is the predominant presenting symptom
      followed by burning sensation, dryness, scaling, oozing, and loss of hair.
      Examination revealed that eczematous lesion was the most common (69.8%) reaction
      pattern followed by xerosis, desquamation, excoriation, erythema, morbilliform
      eruption, erosion, alopecia, ulceration, acute paronychia, and hyperpigmentation.
      The face was the most common (76.4%) site of affection. CONCLUSION: A sizable
      number of patients of pediatric age group may be affected by "Holi"-related
      dermatoses necessitating precautionary measures.

PMID- 27688443
TI  - Relapse after Oral Terbinafine Therapy in Dermatophytosis: A Clinical and
      Mycological Study.
AB  - BACKGROUND: The incidence of recurrent tinea infections after oral terbinafine
      therapy is on the rise. AIM: This study aims to identify the appearance of
      incomplete cure and relapse after 2-week oral terbinafine therapy in tinea
      corporis and/or tinea cruris. MATERIALS AND METHODS: A total of 100 consecutive
      patients clinically and mycologically diagnosed to have tinea corporis and/or
      tinea cruris were included in the study. The enrolled patients were administered
      oral terbinafine 250 mg once daily for 2 weeks. All clinically cured patients
      were then followed up for 12 weeks to look for any relapse/cure. RESULTS: The
      common dermatophytes grown on culture were Trichophyton rubrum and Trichophyton
      tonsurans in 55% and 20% patients, respectively. At the end of 2-week oral
      terbinafine therapy, 30% patients showed a persistent disease on clinical
      examination while 35% patients showed a persistent positive fungal culture
      (persisters) at this time. These culture positive patients included all the
      clinically positive cases. Rest of the patients (65/100) demonstrated both
      clinical and mycological cure at this time (cured). Over the 12-week follow-up,
      clinical relapse was seen in 22 more patients (relapse) among those who had shown
      clinical and mycological cure at the end of terbinafine therapy. Thus, only 43%
      patients could achieve a long-term clinical and mycological cure after 2 weeks of
      oral terbinafine treatment. Majority of the relapses (16/22) were seen after 8
      weeks of completion of treatment. There was no statistically significant
      difference in the body surface area involvement or the causative organism
      involved between the cured, persister, or relapse groups. CONCLUSIONS: Incomplete
      mycological cure as well as relapse is very common after standard (2-week)
      terbinafine therapy in our patients of tinea cruris/corporis.

PMID- 27688444
TI  - A Prospective Study of Herpes Zoster in Children.
AB  - BACKGROUND: Herpes zoster (HZ) is a dermatomal viral infection, caused by
      reactivation of varicella zoster virus (VZV) that persists in the posterior root
      ganglion. HZ is uncommonly reported in immunocompetent children. It may be due to
      intrauterine VZV infection or secondary to postnatal exposure to VZV at an early
      age. AIMS: Our study was to review clinico-epidemiological data for HZ in
      children for early diagnosis and treatment to prevent complications. MATERIALS
      AND METHODS: A prospective observational study was conducted from January 2013 to
      December 2014. Consecutive cases clinically diagnosed as HZ in the pediatric age
      group were taken up. RESULTS: We report the clinico-epidemiological study of 26
      cases of HZ, their benign course and recovery among children. CONCLUSIONS: HZ is
      a rare disease in childhood. Varicella in early childhood is a risk factor of HZ
      in immunocompromised and immunocompetent children. Childhood zoster occurs in
      either healthy or underlying immunodeficient children. The appearance of HZ in a
      young child does not always imply an underlying immunodeficiency or malignancy.
      But the identification of HZ with or without immunodeficiency is of prime
      importance from the treatment and prognostic point of view and should be
      considered in the differential diagnosis of vesicular eruptions. The prognosis is
      generally good in healthy children.

PMID- 27688445
TI  - Three Hundred Patients Treated with Ultrapulsed 980 nm Diode Laser for Skin
      Disorders.
AB  - The use of lasers in skin diseases is quite common. In contrast to other laser
      types, medical literature about 980 nm ultrapulsed diode laser is sparse in
      dermatology. Herein, we report the use of ultrapulsed diode 980 nm laser in 300
      patients with vascular lesions, cysts and pseudocysts, infectious disease, and
      malignant tumors. This laser is a versatile tool with excellent safety and
      efficacy in the hands of the experienced user. 

PMID- 27688449
TI  - IJD((r)) WINDOW.

PMID- 27688446
TI  - Efficacy of Intense Pulsed Light Therapy in the Treatment of Facial Acne
      Vulgaris: Comparison of Two Different Fluences.
AB  - BACKGROUND: Acne vulgaris is the most common disease of the skin affecting
      adolescents and young adults causing psychological distress. The combination of
      antibiotic resistance, adverse effects of topical and systemic anti acne
      medications and desire for high tech approaches have all led to new enthusiasm
      for light based acne treatment. Intense pulse light (IPL) therapy has three modes
      of action in acne vulgaris i.e., photochemical, photo thermal and photo
      immunological. AIMS: (1) to study efficacy of IPL therapy in facial acne
      vulgaris. (2) To compare two fluences - one normal and other subnormal on right
      and left side of face respectively. METHODS: (Including settings and design and
      statistical analysis used). Total 45 patients in age group 16 to 28 years with
      inflammatory facial acne vulgaris were included in prospective study. Baseline
      data for each patient was recorded. All patients were given 4 sittings of IPL at
      2 weeks interval and were followed for 2 months every 2 weeks. Fluence used was
      35J/cm(2) on right and 20J/cm(2) on left side. Percentage reduction in lesion
      count was calculated at each sitting and follow up and graded as mild (0-25%),
      moderate (26-50%), good (51-75%) and excellent (76-100%). Side effects were
      noted. The results were analysed using Mann-Whitney Test. RESULTS: On right side,
      excellent results were achieved in 10(22%), good in 22(49%) and moderate in
      13(29%) patients. On left side excellent were results achieved in 7(15%), good in
      19(42%) and moderate in 16(43%) patients. There was no statically significant
      difference noted in efficacy of two fluences used in treatment of facial acne
      vulgaris. CONCLUSIONS: IPL is a effective and safe option for inflammatory acne
      vulgaris with minimal reversible side effects. Subnormal fluence is as effective
      as normal fluence in Indian skin.

PMID- 27688447
TI  - Belimumab in Systemic Lupus Erythematosus.
AB  - Belimumab is the only approved biological agent for the treatment of systemic
      lupus erythematosus (SLE). It is a fully humanized IgG1gamma monoclonal antibody
      directed against soluble B lymphocyte stimulator (BLyS). It is indicated as an
      add-on therapy for the treatment of adult patients with active, autoantibody
      positive SLE, who are receiving standard therapy. Belimumab is generally well
      tolerated, common adverse effects include infections, infusion reactions,
      hypersensitivity, headache, nausea, and fatigue. Psychiatric events including
      suicidal tendency, progressive multifocal leukoencephalopathy and malignancies
      too have been reported. Apart from SLE, the drug is also being tried for other
      autoimmune disorders. 

PMID- 27688448
TI  - Folliculotropic Mycosis Fungoides: Clinical and Histologic Features in Five
      Patients.
AB  - BACKGROUND: Alopecia can be a manifestation of mycosis fungoides (MF); however,
      the prevalence is unknown. AIMS: We sought to describe the clinicopathologic
      presentation of alopecia in patients with diagnosis of MF. METHODS: A
      retrospective analysis of patients with biopsy-proven MF, who were evaluated at
      our cancer center from 2002 to 2012, was performed to identify patients with
      alopecia. RESULTS: Five patients with alopecia were identified from reviewing of
      157 patients with MF. The male:female ratio was 3:2, and the mean age of patients
      was 42.8 years. Two of these patients showed patchy hair loss on scalp which was
      clinically identical to alopecia areata. In remaining three patients, hair loss
      was seen in areas of MF lesions, and epidermal changes consisted of patch- and
      plaque-type lesions of MF, tumors, and follicular lesions (follicular MF) were
      also present. In two of these patients, lymphadenopathy without any visceral
      involvement was detected. CONCLUSIONS: Alopecia was observed in 5 (3.18%)
      patients with MF, which makes it a rare finding, which included alopecia areata
      like patchy loss in 2 and alopecia within MF lesions in 3.

PMID- 27688450
TI  - Inpatient Dermatology: Characteristics of Patients and Admissions in a Tertiary
      Level Hospital in Eastern India.
AB  - INTRODUCTION: Dermatology is primarily a non-acute, outpatient-centered clinical
      specialty, but substantial number of patients need indoor admission for adequate
      management. Over the years, the need for inpatient facilities in Dermatology has
      grown manifold; however, these facilities are available only in some tertiary
      centers. AIMS AND OBJECTIVES: To analyze the characteristics of the diseases and
      outcomes of patients admitted in the dermatology inpatient Department of a
      tertiary care facility in eastern India. MATERIALS AND METHODS: We undertook a
      retrospective analysis of the admission and discharge records of all patients,
      collected from the medical records department, admitted to our indoor facility
      from 2011 to 2014. The data thus obtained was statistically analyzed with special
      emphasis on the patient's demographic profile, clinical diagnosis, final outcome,
      and duration of stay. RESULTS AND ANALYSIS: A total of 375 patients were admitted
      to our indoor facility during the period. Males outnumbered females, with the
      median age in the 5th decade. Immunobullous disorders (91 patients, 24.27%) were
      the most frequent reason for admissions, followed by various causes of
      erythroderma (80 patients, 21.33%) and infective disorders (73 patients, 19.47%).
      Other notable causes included cutaneous adverse drug reactions, psoriasis,
      vasculitis, and connective tissue diseases. The mean duration of hospital stay
      was 22.2+/-15.7 days; ranging from 1 to 164 days. Majority of patients (312,
      83.2%) improved after hospitalization; while 29 (7.73%) patients died from their
      illness. About 133 patients (35.64%) required referral services during their
      stay, while 8 patients (2.13%) were transferred to other departments for suitable
      management. CONCLUSION: Many dermatoses require inpatient care for their optimum
      management. Dermatology inpatient services should be expanded in India to cater
      for the large number of cases with potentially highly severe dermatoses.

PMID- 27688451
TI  - Pustular Psoriasis Occurring on the Striae Distensae: An Umpteenth Example of
      Immunocompromised Cutaneous District.

PMID- 27688452
TI  - Pachyonychia Congenita: New Classification and Diagnosis.

PMID- 27688453
TI  - Marfanoid Hypermobility Syndrome: Reminscising a Forgotten Entity....

PMID- 27688454
TI  - Angioma Serpiginosum in a Patchy and Blaschkoid Distribution: A Rare Condition
      with an Unconventional Presentation.

PMID- 27688455
TI  - Degos Disease: A Murderous Menace.

PMID- 27688456
TI  - Cutaneous Larva Migrans: Presentation at an Unusual Site.

PMID- 27688457
TI  - Keratotic Papules and Scars in a Young Boy.

PMID- 27688458
TI  - CD8-positive Mycosis Fungoides Masquerading as Pyoderma Gangrenosum.
AB  - Mycosis fungoides (MF), a primary cutaneous T-cell lymphoma, accounts for <1% of
      non-Hodgkin lymphomas. The diagnosis of classic MF is based on a constellation of
      typical clinical presentation, histopathology, immunohistochemistry, and T-cell
      monoclonality detected by molecular studies. Rarely, atypical clinical
      presentation may occur. The typical immunohistochemical phenotype is, CD2 +ve,
      CD3 +ve, CD5 +ve, CD4 +ve, and CD8 - ve. Here, we report a rare case of CD8 +ve
      MF in a 43-year-male patient who was clinically diagnosed as pyoderma gangrenosum
      initially. The atypical presentation and rarity of such case have prompted this
      report. 

PMID- 27688459
TI  - Heterozygous Cylindromatosis Gene Mutation c.1628_1629delCT in a Family with
      Brook-Spiegler Syndrome.
AB  - Brooke-Spiegler Syndrome (BSS) is a rare genodermatosis characterized by the
      progressive formation of adnexal skin tumors in the scalp and face, mainly
      trichoepitheliomas, cylindromas, and spiradenomas. It has also been associated
      with salivary glands neoplasms. It is due to mutations in the tumor suppressor
      gene cylindromatosis (CYLD gene) localized on chromosome 16q12-q13. Around 93
      mutations have been described. The study of CYLD gene in patients and their
      relatives is of vital importance to establish the molecular diagnosis and offer
      appropriate genetic counseling. There is a low risk of malignancy and patients
      require long-term follow-up. A case of BSS in a family is described. The
      existence of the genetic mutation at the CYLD gene c. 1628_1629delCT in three of
      the women affected was demonstrated. This mutation has only been described once
      in a previous study. 

PMID- 27688460
TI  - Experience of Varied Presentation of Chronic Progressive Disseminated
      Histoplasmosis in Immunocompetent Patients: A Diagnostic Conundrum.
AB  - We report two cases of chronic progressive disseminated histoplasmosis with
      unusual and rare clinical picture in a patient with no underlying risk factor.
      One 50-year-old male, presented with hoarseness of voice, chronic cough, with a
      history of nonresponding anti-tubercular therapy, revealed mucocutaneous lesions
      on examination. Fungating vocal cord lesions were visualized on bronchoscopy,
      raised suspicion of carcinoma. The second case, a 22-year-old female, referred to
      hospital with suspected vasculitis, with complaints of "off and on" fever with
      decreased oral intake, arthralgia, who later developed generalized nodular skin
      eruptions. On investigation, human immunodeficiency virus test was found to be
      negative in both the cases. Histopathological findings of skin biopsy, adrenal
      and bone marrow aspirates raised suspicion, whereas fungal cultures confirmed
      Histoplasma infection. Although diagnosis was delayed, but both of them were
      successfully treated with amphotericin B. 

PMID- 27688461
TI  - Hyaline Fibromatosis Syndrome: A Rare Inherited Disorder.
AB  - Hyaline fibromatosis syndrome (HFS) is rare autosomal recessive disease
      characterized by the deposition of amorphous hyaline material in skin and
      visceral organs. It represents a disease spectrum with infantile systemic
      hyalinosis (ISH) being the severe form and juvenile hyaline fibromatosis (JHF)
      being the mild form. Dermatologic manifestations include thickened skin, perianal
      nodules, and facial papules, gingival hyperplasia, large subcutaneous tumors on
      the scalp, hyperpigmented plaques over the metacarpophalangeal joints and
      malleoli, and joint contractures. ISH shows a severe visceral involvement,
      recurrent infections, and early death. We report a case of 2.5-year-old female
      patient who presented with HFS who had overlapping features of both ISH and JHF.
      To the best of our knowledge, very few cases of HFS have been reported in Indian
      literature till date. 

PMID- 27688462
TI  - Borderline Tuberculoid Leprosy Associated with Histoid Leprosy.
AB  - Coexistence of two immunologically diverse forms of leprosy in an individual is
      very rare. Herein, we report a case of association of borderline tuberculoid (BT)
      leprosy with histoid leprosy (HL) in a young immune competent male. He was
      diagnosed as a case of BT leprosy 10 years ago and now presented with multiple
      papules and nodules. Histopathological examination of biopsy taken from patch and
      nodule showed features of BT and HL, respectively. 

PMID- 27688463
TI  - Multiple Eruptive Dermatofibromas Masquerading as Cutaneous Lymphoma.
AB  - A 34-year-old male came with complaints of multiple firms to hard nontender,
      nonitchy nodules, measuring 2 cm * 2 cm to 1 cm * 1.5 cm, present predominantly
      over the lower limbs. This condition started 5 years back as a single nodule over
      the thigh but gradually increased in number and size with time to involve both
      lower limbs. A differential diagnosis of cutaneous lymphoma and dermatofibroma
      was considered. He underwent a biopsy and immunohistochemistry for the same which
      were consistent with hemosiderotic histiocytoma and positive for vimentin. The
      patient was advised surgical excision for the same. The occurrence of multiple
      dermatofibromas although rare has been reported in a few case reports; however,
      the occurrence of multiple dermatofibromas of the hemosiderotic variant has not
      been documented yet. 

PMID- 27688464
TI  - Generalized Morphea following Radiotherapy for an Intracranial Tumor.
AB  - Morphea is a localized scleroderma variety which can be circumscribed or
      generalized and is characterized by sclerotic plaques developing on trunk and
      limbs. Surgery and radiation have been implicated as etiological factors for the
      development of morphea. Majority of the radiation-induced morphea cases have
      occurred in patients with breast cancer. The affected areas have been generally
      restricted to the area of radiation and nearby surrounding area in most of the
      reported cases. We hereby report a case of a 27-year-old male who developed
      radiation-induced progressive generalized morphea after getting radiotherapy for
      an intracranial tumor. His condition improved after dexamethasone
      cyclophosphamide pulse therapy. With increased incidence of cancer worldwide and
      radiotherapy as a modality of treatment, it is imperative to follow the patient
      and look for the development of morphea which itself is a debilitating disease. 

PMID- 27688465
TI  - Linear Non Scarring Alopecia of the Scalp: A Rare Manifestation of Lupus
      Panniculitis.
AB  - Alopecia in a linear pattern is very rare with only a few cases reported in the
      medical literature. We report a case of linear non scarring alopecia involving
      the scalp in a 17-year-old boy with a histological diagnosis of lupus
      panniculitis. We report this case because of its rarity and also the inclusion of
      this entity as one of the rare differential of non scarring alopecia. 

PMID- 27688466
TI  - Granular IgM Deposition at Basement Membrane Zone in an Infant with Diffuse
      Cutaneous Mastocytosis.
AB  - Diffuse Cutaneous mastocytosis (DCM) occurs due to abnormal accumulation of mast
      cells in the skin. We report an 8-month-old infant presented papulovesicular
      lesions, predominantly on the trunk. Skin biopsy revealed subepidermal bulla,
      interspersed with mast cells, eosinophils and neutrophils. Direct
      immunofluorescence microscopy of perilesional skin revealed nonspecific
      deposition of IgM in granular pattern along the dermoepidermal junction. 

PMID- 27688467
TI  - Idiopathic Eruptive Macular Pigmentation with Papillomatosis: An Unfamiliar
      Entity.

PMID- 27688468
TI  - Pfeifer-Weber-Christian Disease during Pregnancy Successfully Treated with
      Corticosteroids.

PMID- 27688471
TI  - SNMMI Comment on the 2016 Society of Surgical Oncology "Choosing Wisely"
      Recommendation on the Use of PET/CT in Colorectal Cancer.

PMID- 27688469
TI  - Optical Imaging of Ionizing Radiation from Clinical Sources.
AB  - Nuclear medicine uses ionizing radiation for both in vivo diagnosis and therapy.
      Ionizing radiation comes from a variety of sources, including x-rays, beam
      therapy, brachytherapy, and various injected radionuclides. Although PET and
      SPECT remain clinical mainstays, optical readouts of ionizing radiation offer
      numerous benefits and complement these standard techniques. Furthermore, for
      ionizing radiation sources that cannot be imaged using these standard techniques,
      optical imaging offers a unique imaging alternative. This article reviews optical
      imaging of both radionuclide- and beam-based ionizing radiation from high-energy
      photons and charged particles through mechanisms including radioluminescence,
      Cerenkov luminescence, and scintillation. Therapeutically, these visible photons
      have been combined with photodynamic therapeutic agents preclinically for
      increasing therapeutic response at depths difficult to reach with external light
      sources. Last, new microscopy methods that allow single-cell optical imaging of
      radionuclides are reviewed.

PMID- 27688470
TI  - NAMPT Inhibitor GMX1778 Enhances the Efficacy of 177Lu-DOTATATE Treatment of
      Neuroendocrine Tumors.
AB  - : Neuroendocrine tumors (NETs) can be treated by peptide receptor radionuclide
      therapy using radiolabeled somatostatin analogs. However, the efficacy of such
      treatment is low and needs to be optimized. Our study evaluated the potential
      radiosensitizing effects of inhibition of nicotineamide phosphoribosyltransferase
      on 177Lu-DOTATATE treatment in a NET model. METHODS: Nude mice xenografted with
      the human NET cell line GOT1 were treated with semiefficient doses of 177Lu
      DOTATATE (7.5 MBq, intravenously) or the nicotineamide phosphoribosyltransferase
      inhibitor GMX1778 (100 mg/kg/wk, orally). RESULTS: Median time to tumor
      progression (tumor volume larger than at day 0) was 3 d for controls, 7 d for
      single-dose GMX1778, 28 d for single-dose 177Lu-DOTATATE, 35 d for 3 weekly doses
      of GMX1778, and 98 d for combined treatment with 177Lu-DOTATATE and GMX1778 * 1.
      After 177Lu-DOTATATE and 3 weekly doses of GMX1778, none of the tumors progressed
      within 120 d. CONCLUSION: GMX1778 enhances the efficacy of 177Lu-DOTATATE
      treatment and induces a prolonged antitumor response.

PMID- 27688472
TI  - Evaluation of Spleen Glucose Metabolism Using 18F-FDG PET/CT in Patients with
      Febrile Autoimmune Disease.
AB  - The purpose of this study was to evaluate the clinical significance of 18F-FDG
      uptake by the spleen in patients with autoimmune disease. Methods: We
      retrospectively reviewed Severance Hospital's electronic medical records of
      patients hospitalized for the evaluation of fever who underwent 18F-FDG PET/CT.
      We found 91 patients with autoimmune diseases and 101 patients with localized
      infection. 18F-FDG uptake was assessed by measuring SUV in the spleen and liver.
      The spleen-to-liver ratio of the SUVmean (SLRmean) was calculated. Clinical and
      laboratory parameters were collected and evaluated for association with SLRmean
      In-hospital mortality was defined as all-cause mortality during hospital
      admission for fever. Results: SLRmean was significantly higher in autoimmune
      disease than in localized infectious disease (1.28 +/- 0.43 vs. 0.91 +/- 0.21, P
      < 0.001). In autoimmune disease, SLRmean was correlated with monocytes, aspartate
      aminotransferase, alanine aminotransferase, albumin, and ferritin. Analysis of
      receiver-operating-characteristic curves revealed that in comparison with
      laboratory parameters, SLRmean had the highest performance in differentiating
      autoimmune from localized infectious disease. Multivariate logistic regression
      analysis demonstrated that high SLRmean and low platelets were significantly
      associated with in-hospital mortality in febrile autoimmune disease. Conclusion:
      These findings suggest that spleen glucose metabolism is increased in febrile
      autoimmune disease. Spleen 18F-FDG uptake may provide information useful in
      differentiating febrile autoimmune disease from localized infectious disease and
      predicting clinical outcomes in febrile autoimmune disease.

PMID- 27688473
TI  - Repeatability of 18F-FLT PET in a Multicenter Study of Patients with High-Grade
      Glioma.
AB  - Quantitative 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET has potential as a
      noninvasive tumor biomarker for the objective assessment of response to
      treatment. To guide interpretation of these quantitative data, we evaluated the
      repeatability of 18F-FLT PET as part of a multicenter trial involving patients
      with high-grade glioma. Methods:18F-FLT PET was performed on 10 patients with
      recurrent high-grade glioma at 5 different institutions within the Adult Brain
      Tumor Consortium trial ABTC1101. Data were acquired according to a double
      baseline protocol in which PET examinations were repeated within 2 d of each
      other with no intervening treatment. On each of the 2 imaging days, dedicated
      brain PET was performed at 2 time points, 1 and 3 h after 18F-FLT administration.
      Tumor SUVs and related parameters were measured at a central laboratory using
      various volumes of interest: isocontour at 30% of the maximum pixel
      (SUVmean_30%), gradient-based segmentation (SUVmean_gradient), the maximum pixel
      (SUVmax), and a 1-mL sphere at the region of highest uptake (SUVpeak).
      Repeatability coefficients (RCs) were calculated from the relative differences
      between corresponding SUV measurements obtained on the 2 d. Results: RCs for
      tumor SUVs were 22.5% (SUVmean_30%), 23.8% (SUVmean_gradient), 23.2% (SUVmax),
      and 18.5% (SUVpeak) at 1 h after injection. Corresponding data at 3 h were 22.4%,
      25.0%, 27.3%, and 23.6%. Normalizing the tumor SUV data with reference to a
      background region improved repeatability, and the most stable parameter was the
      tumor-to-background ratio derived using SUVpeak (RC, 16.5%). Conclusion: SUV
      quantification of 18F-FLT uptake in glioma had an RC in the range of 18%-24% when
      imaging began 1 h after 18F-FLT administration. The volume-of-interest
      methodology had a small but not negligible influence on repeatability, with the
      best performance obtained using SUVpeak Although changes in 18F-FLT SUV after
      treatment cannot be directly interpreted as a change in tumor proliferation, we
      have established ranges beyond which SUV differences are likely due to legitimate
      biologic effects.

PMID- 27688474
TI  - Fission-Produced 99Mo Without a Nuclear Reactor.
AB  - 99Mo, the parent of the widely used medical isotope 99mTc, is currently produced
      by irradiation of enriched uranium in nuclear reactors. The supply of this
      isotope is encumbered by the aging of these reactors and concerns about
      international transportation and nuclear proliferation. Methods: We report
      results for the production of 99Mo from the accelerator-driven subcritical
      fission of an aqueous solution containing low enriched uranium. The predominately
      fast neutrons generated by impinging high-energy electrons onto a tantalum
      convertor are moderated to thermal energies to increase fission processes. The
      separation, recovery, and purification of 99Mo were demonstrated using a recycled
      uranyl sulfate solution. Conclusion: The 99Mo yield and purity were found to be
      unaffected by reuse of the previously irradiated and processed uranyl sulfate
      solution. Results from a 51.8-GBq 99Mo production run are presented.

PMID- 27688475
TI  - A Randomized Feasibility Study of 18F-Fluoroestradiol PET to Predict Pathologic
      Response to Neoadjuvant Therapy in Estrogen Receptor-Rich Postmenopausal Breast
      Cancer.
AB  - The aim of this study was to explore the ability of 18F-fluoroestradiol (18F-FES)
      PET/CT imaging to predict pathologic response to neoadjuvant therapy in
      postmenopausal women with estrogen receptor (ER)-rich breast cancer. Methods:
      This was a prospective, single-center study conducted as a substudy of the
      neoadjuvant study of chemotherapy versus endocrine therapy in postmenopausal
      patients with primary breast cancer (NEOCENT) trial. Patients with ER-rich breast
      cancer were randomized to neoadjuvant chemotherapy (NC) or neoadjuvant endocrine
      therapy (NET). The baseline SUVmax of 18F-FES PET/CT was measured. The pathologic
      response was assessed by the Miller-Payne system as nonresponse (grades 1 and 2)
      and response (grades 3-5). Results: Twenty-six patients were enrolled, with
      pathologic response achieved in 25 (NC, 12; NET, 13). Two patients achieved
      pathologic complete response after NC, but the remaining 23 patients had residual
      disease after NC or NET. Eight of 12 patients responded to NC, and 4 of 13 to
      NET; the difference was marginally significant (P = 0.07). In the NC group, the 2
      patients with 18F-FES-negative tumors and none of the 10 patients with 18F-FES
      avid tumors achieved pathologic complete response (P = 0.02). No difference in
      the SUVmax between responders and nonresponders was observed in either group.
      However, 5 of 7 NC patients with a baseline SUVmax of less than 7.3 achieved
      pathologic response, whereas none of the 5 NET patients with an SUVmax of less
      than 7.3 were responders (P = 0.03). The SUVmax values of the NC group were
      negatively correlated with percentage reduction of tumor cellularity (r = -0.63,
      P = 0.03), whereas those of the NET group showed positive correlation (r = 0.62,
      P = 0.02). During the median follow-up of 74 mo (range, 44-85 mo), recurrence
      occurred in only 4 NET patients. In patients with an SUVmax of less than 7.3,
      recurrence occurred in none of the 8 NC patients and 2 of the 5 NET patients (P =
      0.13). Conclusion: Postmenopausal women who are ER-positive, but 18F-FES
      negative, may benefit from NC rather than NET. 18F-FES PET/CT has the potential
      to predict response to neoadjuvant therapy in postmenopausal women with ER-rich
      breast cancer.

PMID- 27688476
TI  - Optimization of Image Reconstruction for 90Y Selective Internal Radiotherapy on a
      Lutetium Yttrium Orthosilicate PET/CT System Using a Bayesian Penalized
      Likelihood Reconstruction Algorithm.
AB  - Imaging on a gamma-camera with 90Y after selective internal radiotherapy (SIRT)
      may allow for verification of treatment delivery but suffers relatively poor
      spatial resolution and imprecise dosimetry calculation. 90Y PET/CT imaging is
      possible on 3-dimensional, time-of-flight machines; however, images are usually
      poor because of low count statistics and noise. A new PET reconstruction software
      using a Bayesian penalized likelihood (BPL) reconstruction algorithm (termed
      Q.Clear) was investigated using phantom and patient scans to optimize the
      reconstruction for post-SIRT imaging and clarify whether BPL leads to an
      improvement in clinical image quality using 90Y. Methods: Phantom studies over an
      activity range of 0.5-4.2 GBq were performed to assess the contrast recovery,
      background variability, and contrast-to-noise ratio for a range of BPL and
      ordered-subset expectation maximization (OSEM) reconstructions on a PET/CT
      scanner. Patient images after SIRT were reconstructed using the same parameters
      and were scored and ranked on the basis of image quality, as assessed by visual
      evaluation, with the corresponding SPECT/CT Bremsstrahlung images by 2
      experienced radiologists. Results: Contrast-to-noise ratio was significantly
      better in BPL reconstructions when compared with OSEM in phantom studies. The
      patient-derived BPL and matching Bremsstrahlung images scored higher than OSEM
      reconstructions when scored by radiologists. BPL with a beta value of 4,000 was
      ranked the highest of all images. Deadtime was apparent in the system above a
      total phantom activity of 3.3 GBq. Conclusion: BPL with a beta value of 4,000 is
      the optimal image reconstruction in PET/CT for confident radiologic reading when
      compared with other reconstruction parameters for 90Y imaging after SIRT imaging.
      Activity in the field of view should be below 3.3 GBq at the time of PET imaging
      to avoid deadtime losses for this scanner.

PMID- 27688477
TI  - Cure of Human Ovarian Carcinoma Solid Xenografts by Fractionated alpha
      Radioimmunotherapy with 211At-MX35-F(ab')2: Influence of Absorbed Tumor Dose and
      Effect on Long-Term Survival.
AB  - The goal of this study was to investigate whether targeted alpha-therapy can be
      used to successfully treat macrotumors, in addition to its established role for
      treating micrometastatic and minimal disease. We used an intravenous fractionated
      regimen of alpha-radioimmunotherapy in a subcutaneous tumor model in mice. We
      aimed to evaluate the absorbed dose levels required for tumor eradication and
      growth monitoring, as well as to evaluate long-term survival after treatment.
      Methods: Mice bearing subcutaneous tumors (50 mm3, NIH:OVCAR-3) were injected
      repeatedly (1-3 intravenous injections 7-10 d apart, allowing bone marrow
      recovery) with 211At-MX35-F(ab')2 at different activities (close to acute
      myelotoxicity). Mean absorbed doses to tumors and organs were estimated from
      biodistribution data and summed for the fractions. Tumor growth was monitored for
      100 d and survival for 1 y after treatment. Toxicity analysis included body
      weight, white blood cell count, and hematocrit. Results: Effects on tumor growth
      after fractionated alpha-radioimmunotherapy with 211At-MX35-F(ab')2 was strong
      and dose-dependent. Complete remission (tumor-free fraction, 100%) was found for
      tumor doses of 12.4 and 16.4 Gy. The administered activities were high, and long
      term toxicity effects (<=60 wk) were clear. Above 1 MBq, the median survival
      decreased linearly with injected activity, from 44 to 11 wk. Toxicity was also
      seen by reduced body weight. White blood cell count analysis after alpha
      radioimmunotherapy indicated bone marrow recovery for the low-activity groups,
      whereas for high-activity groups the reduction was close to acute myelotoxicity.
      A decrease in hematocrit was seen at a late interval (34-59 wk after therapy).
      The main external indication of poor health was dehydration. Conclusion: Having
      observed complete eradication of solid tumor xenografts, we conclude that
      targeted alpha-therapy regimens may stretch beyond the realm of micrometastatic
      disease and be eradicative also for macrotumors. Our observations indicate that
      at least 10 Gy are required. This agrees well with the calculated tumor control
      probability. Considering a relative biological effectiveness of 5, this dose
      level seems reasonable. However, complete remission was achieved first at
      activity levels close to lethal and was accompanied by biologic effects that
      reduced long-term survival.

PMID- 27688478
TI  - Hybrid Surgical Guidance: Does Hardware Integration of gamma- and Fluorescence
      Imaging Modalities Make Sense?
AB  - The clinically applied hybrid tracer indocyanine green-99mTc-nanocolloid enables
      combined radio- and fluorescence image guidance during sentinel node (SN) biopsy
      procedures. To provide optimal surgical guidance, this tracer requires the
      presence of both gamma- and fluorescence modalities in the operating room. We
      reasoned that the combination or integration of these modalities could further
      evolve the hybrid surgical guidance concept. To study this potential, we
      clinically applied 2 setups that included the combination of gamma-detection
      modalities and an open surgery fluorescence camera. Methods: To attach the
      fluorescence camera (VITOM) to either a gamma-ray detection probe (GP; VITOM-GP)
      or a portable gamma-camera (GC; Vitom GC), clip-on brackets were designed and
      printed in 3-dimensional sterilizable RC31. Both combined modalities were
      evaluated in, respectively, 5 and 6 patients with penile cancer during an SN
      biopsy procedure using indocyanine green-99mTc-nanocolloid. Intraoperatively,
      radio- and fluorescence-guided SN detection rates were scored at working
      distances of 0, 10, 20, and 30 cm for both combinations. Results: Using the VITOM
      GP combination, we evaluated 9 SNs. gamma-tracing rates were shown to be 100%,
      88.9%, 55.6%, and 55.6% at a respective working distance of 0, 10, 20, and 30 cm.
      Detection rates for the fluorescence imaging-based detection were found to be
      100%, 77.8%, and 77.8%, at respective working distances of 10, 20, and 30 cm.
      When the VITOM-GC setup was used, all 10 intraoperatively evaluated SNs could be
      visualized with the gamma-camera independent of the working distance.
      Fluorescence detection rates were 90%, 80%, and 80% at 10-, 20-, and 30-cm
      working distances. The integrated detection modalities were shown to work
      synergistically; overall the, GC was most valuable for rough localization (10- to
      30-cm range) of the SNs, the GP for providing convenient real-time acoustic
      feedback, whereas fluorescence guidance allowed detailed real-time SN
      visualization. Conclusion: Our findings suggest that full integration of a
      fluorescence camera with gamma-detector (GP or GC) can be of value when a hybrid,
      radioactive and fluorescent tracer is used.

PMID- 27688479
TI  - 18F-FDG PET in Posterior Cortical Atrophy and Dementia with Lewy Bodies.
AB  - Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) have both
      been associated with occipital lobe hypometabolism on 18F-FDG PET, whereas
      relative sparing of posterior cingulate metabolism compared with precuneus/cuneus
      (i.e., cingulate island sign) is a feature of DLB. We aimed to determine whether
      patterns of hypometabolism or the cingulate island sign differed between PCA and
      DLB. Methods: Sixteen clinically diagnosed PCA and 13 probable DLB subjects
      underwent 18F-FDG PET. All PCA subjects showed beta-amyloid deposition on PET
      scanning. Regional hypometabolism was assessed compared with a control cohort (n
      = 29) using voxel- and region-level analyses in statistical parametric mapping. A
      ratio of metabolism in the posterior cingulate to precuneus plus cuneus was
      calculated to assess the cingulate island sign. In addition, the 18F-FDG PET
      scans were visually assessed to determine whether the cingulate island sign was
      present in each subject. Results: PCA and DLB showed overlapping patterns of
      hypometabolism involving the lateral occipital lobe, lingual gyrus, cuneus,
      precuneus, posterior cingulate, inferior parietal lobe, supramarginal gyrus,
      striatum, and thalamus. However, DLB showed greater hypometabolism in the medial
      occipital lobe, orbitofrontal cortex, anterior temporal lobe, and caudate nucleus
      than PCA, and PCA showed more asymmetric patterns of hypometabolism than DLB. The
      cingulate island sign was present in both DLB and PCA, although it was more
      asymmetric in PCA. Conclusion: Regional hypometabolism overlaps to a large degree
      between PCA and DLB, although the degree of involvement of the frontal and
      anterior temporal lobes and the presence of asymmetry could be useful in
      differential diagnosis.

PMID- 27688481
TI  - Quantitative Accuracy and Lesion Detectability of Low-Dose 18F-FDG PET for Lung
      Cancer Screening.
AB  - Lung cancer remains responsible for more deaths worldwide than any other cancer,
      but recently there has been a significant shift in the clinical paradigm
      regarding the initial management of subjects at high risk for this disease. Low
      dose CT has demonstrated significant improvements over planar x-ray screening for
      patient prognoses and is now performed in the United States. Specificity of this
      modality, however, is poor, and the additional information from PET has the
      potential to improve its accuracy. Routine screening requires consideration of
      the effective dose delivered to the patient, and this work investigates image
      quality of PET for low-dose conditions, in the context of lung lesion
      detectability. Reduced radiotracer doses were simulated by randomly discarding
      counts from clinical lung cancer scans acquired in list-mode. Bias and
      reproducibility of lesion activity values were relatively stable even at low
      total counts of around 5 million trues. Additionally, numeric observer models
      were developed and trained with the results of 2 physicians and 3 postdoctoral
      researchers with PET experience in a detection task; detection sensitivity of the
      observers was well correlated with lesion signal-to-noise ratio. The models were
      used prospectively to survey detectability of lung cancer lesions, and the
      findings suggested a lower limit around 10 million true counts for maximizing
      performance. Under the acquisition parameters used in this study, this translates
      to an effective patient dose of less than 0.4 mSv, potentially allowing a
      complete low-dose PET/CT lung screening scan to be obtained under 1 mSv.

PMID- 27688480
TI  - Associations Between Somatic Mutations and Metabolic Imaging Phenotypes in Non
      Small Cell Lung Cancer.
AB  - PET-based radiomics have been used to noninvasively quantify the metabolic tumor
      phenotypes; however, little is known about the relationship between these
      phenotypes and underlying somatic mutations. This study assessed the association
      and predictive power of 18F-FDG PET-based radiomic features for somatic mutations
      in non-small cell lung cancer patients. Methods: Three hundred forty-eight non
      small cell lung cancer patients underwent diagnostic 18F-FDG PET scans and were
      tested for genetic mutations. Thirteen percent (44/348) and 28% (96/348) of
      patients were found to harbor epidermal growth factor receptor (EGFR) or Kristen
      rat sarcoma viral (KRAS) mutations, respectively. We evaluated 21 imaging
      features: 19 independent radiomic features quantifying phenotypic traits and 2
      conventional features (metabolic tumor volume and maximum SUV). The association
      between imaging features and mutation status (e.g., EGFR-positive [EGFR+] vs.
      EGFR-negative) was assessed using the Wilcoxon rank-sum test. The ability of each
      imaging feature to predict mutation status was evaluated by the area under the
      receiver operating curve (AUC) and its significance was compared with a random
      guess (AUC = 0.5) using the Noether test. All P values were corrected for
      multiple hypothesis testing by controlling the false-discovery rate (FDRWilcoxon,
      FDRNoether) with a significance threshold of 10%. Results: Eight radiomic
      features and both conventional features were significantly associated with EGFR
      mutation status (FDRWilcoxon = 0.01-0.10). One radiomic feature (normalized
      inverse difference moment) outperformed all other features in predicting EGFR
      mutation status (EGFR+ vs. EGFR-negative, AUC = 0.67, FDRNoether = 0.0032), as
      well as differentiating between KRAS-positive and EGFR+ (AUC = 0.65, FDRNoether =
      0.05). None of the features was associated with or predictive of KRAS mutation
      status (KRAS-positive vs. KRAS-negative, AUC = 0.50-0.54). Conclusion: Our
      results indicate that EGFR mutations may drive different metabolic tumor
      phenotypes that are captured in PET images, whereas KRAS-mutated tumors do not.
      This proof-of-concept study sheds light on genotype-phenotype interactions, using
      radiomics to capture and describe the phenotype, and may have potential for
      developing noninvasive imaging biomarkers for somatic mutations.

PMID- 27688484
TI  - A General Method for Nucleophilic Aromatic Substitution of Aryl Fluorides and
      Chlorides with Dimethylamine using Hydroxide-Assisted Decomposition of N,N
      Dimethylforamide.
AB  - A practical and convenient procedure for the nucleophilic aromatic substitution
      of aryl fluorides and chlorides with dimethylamine was developed using a
      hydroxide assisted, thermal decomposition of N,N-dimethylforamide. These
      conditions are tolerant of nitro, nitrile, aldehyde, ketone, and amide groups but
      will undergo acyl substitution to form amides for methyl esters and acyl
      chlorides. Isolated yields of the products range from 44 - 98%, with the majority
      being greater than 70% for seventeen examples.

PMID- 27688485
TI  - Opposites Detract.

PMID- 27688483
TI  - A Long-lived Mouse Lacking Both Growth Hormone and Growth Hormone Receptor: A New
      Animal Model for Aging Studies.
AB  - Disruption of the growth hormone (GH) signaling pathway promotes insulin
      sensitivity and is associated with both delayed aging and extended longevity. Two
      kinds of long-lived mice-Ames dwarfs (df/df) and GH receptor gene-disrupted
      knockouts (GHRKO) are characterized by a suppressed GH axis with a significant
      reduction of body size and decreased plasma insulin-like growth factor-1 (IGF-1)
      and insulin levels. Ames dwarf mice are deficient in GH, prolactin, and
      thyrotropin, whereas GHRKOs are GH resistant and are dwarf with decreased
      circulating IGF-1 and increased GH. Crossing Ames dwarfs and GHRKOs produced a
      new mouse line (df/KO), lacking both GH and GH receptor. These mice are
      characterized by improved glucose tolerance and increased adiponectin level,
      which could imply that these mice should be also characterized by additional life
      span extension when comparing with GHRKOs and Ames dwarfs. Importantly, our
      longevity experiments showed that df/KO mice maintain extended longevity when
      comparing with N control mice; however, they do not live longer than GHRKO and
      Ames df/df mice. These important findings indicate that silencing GH signal is
      important to extend the life span; however, further decrease of body size in mice
      with already inhibited GH signal does not extend the life span regardless of
      improved some health-span markers.

PMID- 27688486
TI  - General Practice Forward View: a new charter for general practice?

PMID- 27688482
TI  - Impact of Aging on Proprioceptive Sensory Neurons and Intrafusal Muscle Fibers in
      Mice.
AB  - The impact of aging on proprioceptive sensory neurons and intrafusal muscle
      fibers (IMFs) remains largely unexplored despite the central function these cells
      play in modulating voluntary movements. Here, we show that proprioceptive sensory
      neurons undergo deleterious morphological changes in middle age (11- to 13-month
      old) and old (15- to 21-month-old) mice. In the extensor digitorum longus and
      soleus muscles of middle age and old mice, there is a significant increase in the
      number of Ia afferents with large swellings that fail to properly wrap around
      IMFs compared with young adult (2- to 4-month-old) mice. Fewer II afferents were
      also found in the same muscles of middle age and old mice. Although these age
      related changes in peripheral nerve endings were accompanied by degeneration of
      proprioceptive sensory neuron cell bodies in dorsal root ganglia (DRG), the
      morphology and number of IMFs remained unchanged. Our analysis also revealed
      normal levels of neurotrophin 3 (NT3) but dysregulated expression of the tyrosine
      kinase receptor C (TrkC) in aged muscles and DRGs, respectively. These results
      show that proprioceptive sensory neurons degenerate prior to atrophy of IMFs
      during aging, and in the presence of the NT3/TrkC signaling axis.

PMID- 27688487
TI  - The mental health of young people: the view from primary care.

PMID- 27688488
TI  - Childhood bullying: implications for general practice.

PMID- 27688489
TI  - Closing the gap between physical and mental health training.

PMID- 27688490
TI  - Not such friendly banter? GPs and psychiatrists against the systematic
      denigration of their specialties.

PMID- 27688491
TI  - Clinical skills training in UK GP training schemes.

PMID- 27688492
TI  - The Calais 'jungle'.

PMID- 27688493
TI  - General practice workload.

PMID- 27688494
TI  - Bad medicine: the menopause.

PMID- 27688495
TI  - Chronic fatigue syndrome: is the biopsychosocial model responsible for patient
      dissatisfaction and harm?

PMID- 27688496
TI  - Chronic fatigue syndrome and the biopsychosocial model.

PMID- 27688497
TI  - Hypertension in surgical patients: the role of beta-blockers.

PMID- 27688498
TI  - Encouraging medical students to pursue general practice.

PMID- 27688499
TI  - Incidence of cow's milk protein allergy.

PMID- 27688500
TI  - Barriers to advance care planning in primary care.

PMID- 27688501
TI  - Alerts in electronic medical records in primary care to promote colorectal cancer
      screening.

PMID- 27688502
TI  - Prediction rules and POC D-dimer testing as a way to prevent diagnostic delay of
      fatal pulmonary embolism.

PMID- 27688503
TI  - Understanding grief and bereavement.

PMID- 27688504
TI  - Implementing collaborative care and support planning in Islington.

PMID- 27688506
TI  - Bad Medicine: The worried hell.

PMID- 27688505
TI  - Yonder: Acute kidney injury, domestic violence, allergy services, and
      receptionists.

PMID- 27688507
TI  - Escape to the country: challenges of a migrant population for the rural GP.

PMID- 27688508
TI  - Ten Commandments for the resilient practitioner.

PMID- 27688509
TI  - Books: Painkiller Addict: From Wreckage to Redemption - My True Story: Never
      Enough.

PMID- 27688510
TI  - Books: Stressed, Unstressed: Classic Poems to Ease the Mind: Can You be Re-Lit by
      Poetry?

PMID- 27688511
TI  - Books: When Someone You Know Has Depression: Words To Say and Things to Do :
      Recovery and Resilience.

PMID- 27688512
TI  - BJGP Library: On the Edge of the Primeval Forest: Experiences and Observations of
      a Doctor in Equatorial Africa.

PMID- 27688513
TI  - Exhibition: Making Beauty: Elpida Hadzi-Vasileva: Gut Feeling.

PMID- 27688514
TI  - GPs, mums, and the 'Twittersphere'.

PMID- 27688515
TI  - Why are statin prescribing guidelines for primary prevention not always followed
      in primary care?

PMID- 27688516
TI  - Current recommendations in the management of hypothyroidism: developed from a
      statement by the British Thyroid Association Executive.

PMID- 27688517
TI  - Neutrophil gelatinase-associated lipocalin: primary care diagnostic technology
      update.

PMID- 27688519
TI  - Healing doctors through groups: creating time to reflect together.

PMID- 27688518
TI  - Identifying barriers to mental health help-seeking among young adults in the UK:
      a cross-sectional survey.
AB  - BACKGROUND: Despite the high prevalence and burden of mental health problems
      among young people, studies have suggested that they infrequently seek
      professional help. Understanding the barriers to help-seeking is an important
      step towards facilitating early access to mental health services and improving
      psychological wellbeing. AIM: To investigate why young adults may choose not to
      seek any support for an emotional or mental health difficulty. DESIGN AND
      SETTING: A cross-sectional online survey of young adults aged 18-25 from the
      general UK population. METHOD: The survey consisted of an anonymous questionnaire
      that measured psychological distress, help-seeking preferences, and barriers to
      accessing help, which included the Barriers to Access to Care Evaluation (BACE)
      scale and an open-ended question to explore reasons for not seeking help in the
      past. Qualitative feedback was analysed using thematic analysis. RESULTS:
      Overall, 35% of participants (n = 45) who reported having an emotional or mental
      health difficulty did not seek any formal or informal help. The thematic analysis
      revealed that stigmatising beliefs, difficulty identifying or expressing
      concerns, a preference for self-reliance, and difficulty accessing help were
      prominent barrier themes among responders. CONCLUSION: Young adults experiencing
      psychological distress may struggle to access help from others. Stigma and
      negative perceptions surrounding mental health and help-seeking may explain why
      young people are reluctant to approach others for help. Improving public
      awareness of the services and resources that are available, as well as screening
      for psychological distress in primary care services, may be necessary to improve
      mental wellbeing among young adults.

PMID- 27688521
TI  - Improving prescribing and medicine use.

PMID- 27688520
TI  - Can't Look Away: An Eye-Tracking Based Attentional Disengagement Training for
      Depression.
AB  - To address shortcomings of purely reaction-time based attentional bias
      modification (ABM) paradigms, we developed an ABM task that is controlled by eye
      tracking. This task allows to assess and train both disengagement from negative
      pictures and maintained attention to positive pictures. As a proof-of-principle
      study with an unselected student sample, this positive training (PT; N = 44) was
      compared to a negative training (NT; N = 42), which reinforced the opposite
      attentional pattern. Importantly, training trials were completed only if
      participants performed the correct gaze patterns. Results showed that higher
      depression levels were associated with slower disengagement from negative stimuli
      at baseline. As expected, the PT induced longer fixations on positive pictures
      and faster disengagement from negative pictures. The NT showed no changes in
      attentional processes. The groups did not differ in mood reactivity and recovery
      from a stressor. Advantages of using eye-tracking in ABM and potential
      applications of the training are discussed.

PMID- 27688523
TI  - Multimodality pH imaging in a mouse dorsal skin fold window chamber model.
AB  - Upregulate levels of expression and activity of membrane H+ ion pumps in cancer
      cells drives the extracellular pH (pHe,) to values lower than normal.
      Furthermore, disregulated pH is indicative of the changes in glycolytic
      metabolism in tumor cells and has been shown to facilitate extracellular tissue
      remodeling during metastasis Therefore, measurement of pHe could be a useful
      cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality
      in-vivo imaging of pHe in tumorous tissue in a mouse dorsal skin fold window
      chamber (DSFWC) model is described. A custom-made plastic window chamber
      structure was developed that is compatible with both imaging optical and MR
      imaging modalities and provides a model system for continuous study of the same
      tissue microenvironment on multiple imaging platforms over a 3-week period. For
      optical imaging of pHe, SNARF-1 carboxylic acid is injected intravenously into a
      SCID mouse with an implanted tumor. A ratiometric measurement of the fluorescence
      signal captured on a confocal microscope reveals the pHe of the tissue visible
      within the window chamber. This imaging method was used in a preliminary study to
      evaluate sodium bicarbonate as a potential drug treatment to reverse tissue
      acidosis. For MR imaging of pHe the chemical exchange saturation transfer (CEST)
      was used as an alternative way of measuring pHe in a DSFWC model. ULTRAVIST(r), a
      FDA approved x-ray/CT contrast agent has been shown to have a CEST effect that is
      pH dependent. A ratiometric analysis of water saturation at 5.6 and 4.2 ppm
      chemical shift provides a means to estimate the local pHe.

PMID- 27688522
TI  - Fostering Higher Education: A Postsecondary Access and Retention Intervention for
      Youth with Foster Care Experience.
AB  - Most youth in foster care aspire to obtain higher education, but face daunting
      obstacles in doing so. While societal interest and effort to support foster youth
      in achieving higher education has grown, very few supports have evidence to show
      that they are effective at improving postsecondary outcomes. In an effort to
      address the dearth of clearly articulated, evidence-based postsecondary support
      approaches for foster youth, we have developed Fostering Higher Education (FHE),
      a comprehensive, structured, and evaluable postsecondary access and retention
      intervention composed of elements (professional educational advocacy, substance
      abuse prevention, mentoring) that are either evidence based or promising based on
      the scientific literature and their ability to address the outcomes of interest.
      This paper describes the development and youth usability and practitioner
      feasibility testing of the FHE intervention approach, which was developed through
      funding from the National Institute on Drug Abuse. Youth usability feedback was
      primarily positive, with the majority of participants indicating they found the
      FHE activities interesting and useful, and were comfortable participating in
      them. Practitioner feasibility feedback was also primarily positive, with almost
      unanimous ratings of the FHE intervention components as very important to provide
      to youth and that all would be feasible for an organization to implement, though
      the mentoring components were seen as slightly less feasible than other
      components. Next steps and implications of this intervention development process
      are discussed.

PMID- 27688524
TI  - TaqI, FokI, and ApaI Polymorphisms in the Vitamin D Receptor in Behcet's Disease
      in Turkish Population.
AB  - Objectives. In our study we aimed to determine VDR gene polymorphisms in patients
      with Behcet's disease (BD) and neuro-Behcet's disease (NBD) in Turkish
      population. Methods. PBL obtained from 37 patients with BD, 21 patients with NB,
      and 30 healthy controls were investigated. Genomic DNA was extracted from whole
      blood using the QIAamp Blood Kit. VDR ApaI (rs7975232), VDR FokI (rs2228570), and
      VDR TaqI (rs731236) genotyping was performed by real-time polymerase chain
      reaction with SimpleProbe melting-curve analysis. Results. The allelic and
      genotype distributions of FokI and TaqI polymorphisms were not different among
      Behcet's disease, neuro-Behcet's disease, and control subjects in Turkish
      population (p > 0.05). Only the frequency of ApaI A allele in control is higher
      than that in BD (60% versus 38.5%), and the p value is 0.014, but the power is
      not enough to conclude that ApaI A allele is protective in BD in our study. Taken
      together, we found no significant differences between the BD, NBD, and control
      groups regarding the distribution of ApaI, TaqI, and FokI genotype and alleles
      frequencies. Conclusions. Future studies with larger patients' numbers may show
      differences between VDR polymorphisms and Behcet's disease.

PMID- 27688525
TI  - Four Lymphomas in 1 Patient: A Unique Case of Triple Composite Non-Hodgkin
      Lymphoma Followed by Classical Hodgkin Lymphoma.
AB  - Composite lymphomas consist of 2 or more distinct lymphomas occurring in a single
      anatomical site or simultaneously in different sites and can be composed of any
      combination of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, or Hodgkin lymphoma
      (HL). Cases of composite lymphomas with more than 2 lymphomas are extremely rare,
      with only 4 reports in the literature. We report the case of a 49-year-old man
      with a triple composite lymphoma in a single lymph node, consisting of small
      lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma in situ. The
      patient received multiple courses of chemotherapy and an autologous stem cell
      transplant, which resulted in complete remission. Then, 6 years after the stem
      cell transplant, he developed classical HL. This unique case is, to our
      knowledge, the first report of a patient with triple composite lymphoma
      consisting of 3 small mature B-cell NHLs, who subsequently developed a fourth
      lymphoma.

PMID- 27688526
TI  - Gender-Role Portrayals in Television Advertising Across the Globe.
AB  - Although there are numerous studies on gender-role portrayals in television
      advertising, comparative designs are clearly lacking. With content analytical
      data from a total of 13 Asian, American, and European countries, we study the
      stereotypical depiction of men and women in television advertisements. Our sample
      consists of 1755 ads collected in May 2014. Analyzing the gender of the primary
      character and voiceover, as well as the age, associated product categories, home-
      or work setting, and the working role of the primary character, we concluded that
      gender stereotypes in TV advertising can be found around the world. A multilevel
      model further showed that gender stereotypes were independent of a country's
      gender indices, including Hofstede's Masculinity Index, GLOBE's Gender
      Egalitarianism Index, the Gender-related Development Index, the Gender Inequality
      Index, and the Global Gender Gap Index. These findings suggest that gender
      stereotyping in television advertising does not depend on the gender equality
      prevalent in a country. The role of a specific culture in shaping gender
      stereotypes in television advertising is thus smaller than commonly thought.

PMID- 27688528
TI  - The Need to Change.

PMID- 27688527
TI  - The Relationship Between Endorsement of the Sexual Double Standard and Sexual
      Cognitions and Emotions.
AB  - Sexual gender norms promoting sexual prowess for men, but sexual modesty for
      women have been shown to negatively affect sexual and mental health in both men
      and women. Knowledge about the relationship between gender norms and sexual
      cognitions and emotions might further the understanding of continued gender-norm
      conformity. In the present study, we investigated whether and how gendered sexual
      attitudes are related to (positive and negative) sex-related emotions, via sexual
      cognitions (autonomy, body esteem, and approach/avoidance motives for sex). A
      survey was submitted to 293 heterosexually identified, sexually active, Dutch
      (central and southern regions) 18-25 year-olds. Results from a moderated
      mediation model (using structural equation modeling) revealed that women, but not
      men, who more strongly endorsed traditional gender-related sexual attitudes
      experienced significantly less positive and more negative emotions, as a result
      of decreased sexual autonomy and sexual body esteem as well as increased
      avoidance motives for sex. We conclude that, as a result of negative cognitions
      associated with the endorsement of traditional gender norms, women in particular
      are at risk of experiencing negative emotional outcomes in the sexual context. We
      argue that sexual cognitions and emotions deserve explicit attention in sex
      positive and gender-transformative sexuality education, which has been proven to
      be a vital resource for achieving increased gender-equity in sexual and romantic
      relationships.

PMID- 27688529
TI  - Parathyroid Neoplasms: The Army Hospital (Research & Referral) Experience.
AB  - BACKGROUND: Neoplasms of the parathyroid are common but parathyroid carcinoma is
      exceptionally rare. In contrast to most other malignant endocrine tumours that
      are usually less hormonally active, malignant parathyroid tumours are hyper
      functional. Malignant parathyroid tumours pose a diagnostic dilemma for the
      pathologist. OBJECTIVE: To study the clinicopathological profile of a case series
      of parathyroid neoplasms and determine features which facilitate a malignant
      diagnosis. METHODS: A retrospective analysis of seven cases of surgically treated
      parathyroid tumours over a three-year period at a single centre was done.
      Clinical, haematological, biochemical, and radiological data was accrued from
      medical records. The histopathology slides were reviewed along with the
      clinicopathological profile in an attempt to delineate markers of malignancy.
      RESULTS: Patients ranged from 30 to 58 years of age. Males and females were
      approximately equal. Weakness and bone pain were the commonest presenting
      symptoms. Over 50% had significant hypercalcaemia and all had elevated serum
      parathormone. Clinically apparent mass was seen in only one. All tumours were
      successfully localised using CT scan and MRI. Thick fibrous capsule and broad
      septal fibrosis was seen in both the carcinomas; these were thin in the adenomas.
      Mitotic counts of 1-3 per high power field (HPF), capsular invasion and nodal
      metastasis were noted in the malignant tumours. CONCLUSION: Elevated serum
      calcium and parathormone values point to a parathyroid neoplasm. Current imaging
      modalities are successful in localising the tumour preoperatively. Markedly
      elevated serum calcium, broad fibrous bands, mitotic counts and capsular invasion
      are indicators of malignancy.

PMID- 27688530
TI  - Detection of Human Immunodeficiency Virus Type 1 (HIV-1) A/AE Circulating
      Recombinant Form (CRF) in India: Possible Implications.
AB  - BACKGROUND: Rapidly evolving viruses such as human immunodeficiency virus (HIV-1)
      develop marked sequence differences in their genome over the course of an
      epidemic and in individuals infected for longer duration. This is because of the
      error prone reverse transcriptase (RT), which rapidly incorporates mutations
      resulting in genomic diversity, altered cell tropism, immune escape, and variable
      resistance to antiretroviral drugs. As a result, radically different genomic
      combinations may be generated in individuals infected by genetically diverse
      viruses that have mosaic genomes. METHODS: Whole blood sample was collected from
      25 HIV-1 infected patients. Chromosomal DNA was isolated from the patient's
      peripheral blood mononuclear cells (PBMCs). Full-length gag gene (~1.5 kb) was
      amplified. PCR products were subjected to direct automated sequencing. For
      identification of recombinants Simplot version 2.5 was used. RESULTS: Out of 25
      gag genes that were sequenced, the gene amplified from a 29 years old HIV-1
      seropositive male revealed a putative recombinant sequence. This sequence showed
      maximum homology with HIV-1 subtype A. Simplot analysis revealed the sequence to
      be a likely recombinant with the following composition: Initial stretch of 1 to
      200 nucleotides representing AE circulating recombinant form (CRF), 201 to 440
      nucleotides representing HIV-1 subtype A, 441 to 660 nucleotides representing AE
      CRF again, 661 to 700 nucleotides representing HIV-1 subtype A and the remaining
      stretch of the nucleotides from 701 to 1076 representing AE CRF. CONCLUSION: We
      document a putative HIV-1 subtype A/ AE CRF. It is important to monitor various
      CRFs that are being generated and horizontally spread in the community. This has
      significant implications for development of candidate vaccine for India.

PMID- 27688531
TI  - Hepatitis G Virus Infection in Healthy Individuals, Acute Viral Hepatitis and
      Persons at Risk for Parenteral Transmission.
AB  - BACKGROUND: Hepatitis G virus (HGV), transmitted mostly by parenteral route, has
      been under investigation for its role as an agent for viral hepatitis. This study
      was carried out to find out the prevalence of HGV in healthy individuals, multi
      transfused patients with acute viral hepatitis and those under going dialysis.
      METHOD: The study included 200 healthy individuals and 180 patients, comprising
      acute viral hepatitis (100 cases), multi-transfused patients (50 cases) and
      patients undergoing dialysis (30 cases). HGV RNA and Hepatitis C virus (HCV) RNA
      was detected by reverse transcription and polymerase chain reaction (RT-PCR) in
      all. Viral marker studies for hepatitis A, B and E were carried out by ELISA in
      acute viral hepatitis cases. In healthy individuals, in patients with multiple
      transfusions or those undergoing dialysis, marker studies for HBV and HCV were
      carried out. RESULT: The prevalence of HGV in healthy individuals was 2.5%
      (5/200), in non A-E hepatitis 3% (3/100), in multi-transfused patients 4% (2/50)
      and in patients undergoing dialysis 6.67% (2/30). There was no significant
      difference in the prevalence rate of HGV infection in healthy individuals and in
      patients with non A-E hepatitis. CONCLUSION: Depending on prevalence rate, HGV
      could not be implicated as cause of acute viral hepatitis. Persons with
      parenteral risk factor (multiple blood transfusions and those undergoing
      dialysis) had higher prevalence rate as compared to healthy individuals.

PMID- 27688532
TI  - Resistance to Antituberculosis Drugs in Pulmonary Tuberculosis.
AB  - BACKGROUND: Incidence of drug resistance and pattern of susceptibility to
      antitubercular drugs in pulmonary tuberculosis amongst soldiers and their
      families was studied for four years at a military hospital in northwest India.
      METHODS: Identification and susceptibility tests were carried out as per
      procedures laid out in laboratory manual of Tuberculosis Research Centre (TRC),
      Chennai. RESULTS: Of the 172 strains of Mycobacterium tuberculosis (MTB) isolated
      from sputum samples, 150 (87.21%) were sensitive and 22 (12.79%) showed
      resistance to one or more antitubercular drugs. Acquired drug resistance was
      observed in 7 (31.82%) and primary drug resistance in 15 (68.18%) cases. Among 22
      drug resistant cases, who were on short course chemotherapy (SCC), resistance to
      single drug was observed in 12 (54.54%), two drugs in 7 (31.82%) and to three or
      more drugs in 3 (13.64%) isolates. Fourteen (18.14%) strains were resistant to
      Streptomycin, 8 (4.65%) to Rifampicin, 11 (6.40%) to Isoniazid, 1 (0.58%) to
      Pyrazinamide and 2 (1.16%) to Ethambutol. Multidrug resistance was observed in 5
      (2.91%) cases, of which resistance to Isoniazid and Rifampicin was present in 2
      (1.16%) and their combination with other drugs in other 3 (1.74%) isolates.
      CONCLUSIONS: Drug susceptibility pattern to antitubercular drugs is discussed and
      compared with studies from other centres.

PMID- 27688533
TI  - Socio Behavioural Profile of HIV Positive DSC Personnel.
AB  - BACKGROUND: Few human immunodeficiency virus (HIV) positive Defence Security
      Corps (DSC) personnel reported for surveillance at one of the Air Force (AF)
      stations in 1992 and it was appropriate to study socio-behavioural profile of HIV
      positive DSC personnel to determine the reason for their vulnerability. METHOD:
      The study was conducted among 46 HIV positive DSC personnel during 1992-2004 at
      various AF stations. Pretested questionnaires were introduced to the subjects to
      ascertain their demographic, social, educational and behavioural profile vis-a
      vis their HIV-AIDS awareness. RESULTS: Majority of the subjects detected during
      pre-donation screening were middle aged, rural, semiliterate, (56.5%) and
      acquired the disease through heterosexual (95.66%) mode, mostly from commercial
      sex workers (CSWs). All were aware of HIV-AIDS prevention and most of them
      (77.2%) stated that condoms were easily available but 70.7% did not use the same
      for the fear of failure to perform under the influence of liquor. 74% subjects
      were found complying with medical instructions. CONCLUSION: The study brings out
      a discernable gap between the knowledge and practice of safe sex. Adequate
      preventive knowledge did not always result in practice of safe sex.

PMID- 27688534
TI  - Epidemiological Investigation of an Outbreak of Viral Hepatitis.
AB  - BACKGROUND: There was a rise in the number of viral hepatitis cases in a
      regimental training centre in Mar 2003 and an epidemic of viral hepatitis was
      suspected. METHODS: The clinical case sheets and preliminary investigations
      carried out in the local military hospital (MH) were reviewed. A cross sectional
      descriptive epidemiological study was undertaken with survey odf the suspected
      sewage and water pipelines. RESULTS: A total of 36 cases occurred from Mar 2003
      to Apr 2003. There was clustering in time and space suggesting common source
      epidemic. All the 36 serum samples tested for IgM anti HEV antibodies were
      positive. Exploration of the water pipelines revealed sewage contamination due to
      leakage in the pipeline passing close to the sewage line. The overall attack rate
      was 1.44%. CONCLUSION: The outbreak of viral hepatitis in the regimental training
      centre occurred due to sewage contamination of drinking water pipeline.

PMID- 27688535
TI  - HIV Prevention in the Armed Forces: Perceptions and Attitudes of Regimental
      Officers.
AB  - BACKGROUND: Involvement of commanders and regimental officers is believed
      essential for a successful human immunodeficiency virus (HIV) infection
      prevention programme in the armed forces. METHODS: A structured questionnaire was
      sent to 40 different Information, Education and Communication (IEC) nodes to
      elicit the perception and attitude of regimental officers/commanders. From each
      station, 40 regimental officers/commanders were randomly selected and information
      from 1002 valid and completed questionnaires was analysed. RESULTS: Less than 50%
      could correctly assess the burden of HIV/AIDS in the armed forces. Only 41.19%
      felt HIV/AIDS is a problem serious enough to adversely affect operational
      efficiency. Majority had communicated with the troops on the subject of HIV/AIDS.
      The perceived threat of HIV being a problem in own unit was low. Though condom
      was often advocated, the felt need of condom in the unit was not commensurate
      with this advocacy. There were statistically significant differences in the
      perception and attitude among the three services. Only 7.08% of the officers
      emphasised the need of maintaining confidentiality while dealing with a HIV
      positive soldier. CONCLUSION: Energetic advocacy on HIV prevention including
      condom promotion involving the regimental officers is indicated. Wider
      dissemination of surveillance figures generated at AIDS Control Organisation
      (ACO) is needed for apprising them about the menace of HIV in the armed forces.

PMID- 27688536
TI  - Study of Behaviour Problems in a Paediatric Outpatient Department.
AB  - BACKGROUND: Behaviour problems in children still needs precise definition,
      explicit criterion and assessment on multiple paradigms. METHODS: Fifty children
      of the age group 6-14 years, from paediatric outpatient department, selected
      after randomisation were assessed for behaviour problems with the child behaviour
      checklist. The data collected was analysed using appropriate statistical tests.
      RESULTS: 40% children were above cutoff score. Mean child behaviour check list
      (CBCL) score was 40.6. Total of 72% children were from armed forces background of
      whom 9% were siblings of officers. 30.6% children from the armed forces
      background were above the cutoff score. There was no significant difference in
      the behaviour problems between different age groups and sex. There was no
      significant difference in behaviour problems between children of officers, other
      ranks or various income groups. Female children had behaviour problems like "too
      concerned with neatness or cleanliness", "feels has to be perfect" and "argues a
      lot" where as male children had behaviour problems like "Does not feel guilty
      after misbehaving", "argues a lot" and "restless". CONCLUSION: Behaviour problems
      in the subjects were externalizing ones. No specific trend was found in children
      of defence personnel vis-a-vis children of civilian population.

PMID- 27688537
TI  - Outbreak of Scrub Typhus in Jammu - A Report.
AB  - BACKGROUND: Jammu is scrub typhus prone. Scrub typhus is often seen when troops
      move out of permanent locations. METHODS: In a prospective study cases of fever
      reporting to the local military hospital from July to October 2002 were examined
      clinically, investigated and categorised as scrub typhus when Weil Felix readings
      were above 1:160. RESULTS: Twelve cases of scrub typhus were diagnosed during the
      period of study. The clinical features included fever, malaise and conjunctival
      congestion. However rashes were rare and only one had an eschar. Multisystem
      complications occurred in one patient. There was a spatial and temporal
      clustering of cases. Control of outbreak was carried out by 25% benzyl benzoate
      impregnation of clothing, clearing of scrub, residual spray with malathion and
      antirodent measures. CONCLUSION: Scrub typhus outbreaks have been noted whenever
      troops move out of permanent locations to scrub areas.

PMID- 27688539
TI  - Transfusion Transmitted Infections in Armed Forces: Prevalence and Trends.
AB  - BACKGROUND: This study presents data on the prevalence rate of infectious markers
      among voluntary and replacement donors in the blood transfusion service in Armed
      Forces from 2000 to 2004. METHODS: 39,646 units of blood were collected from
      donors during the period from 2000 to 2004. All the samples were screened for
      hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV) 1&2,
      hepatitis C virus (HCV), and by venereal disease research laboratory test (VDRL).
      RESULTS: 24,527 (61.9%) were voluntary donations and 15,119 (38.1%) replacement
      donations. Prevalence of HBsAg had decreased, amongst voluntary donors from 1.67%
      to 0.77% but the positivity rate has not showed significant change.
      Seropositivity of HIV had decreased both in voluntary and replacement donors to
      0.22% and 0.86% respectively. The seropositivity for anti-HCV showed steady
      decrease amongst voluntary donors from 0.46% to 0.20% in 2004, but in replacement
      donors, there was an increase in reactivity rate from 0.43% to 0.65%. CONCLUSION:
      The increased seropositivity for HCV, HIV and HBsAg could be decreased by
      introduction of nucleic acid amplification testing (NAT) in minipools for HCV and
      HIV and introduction of anti-HBcAg (IgM) for hepatitis B virus (HBV) infection.
      But this may not be possible in near future in developing countries due to
      financial constraints. At present implementation of strict donor criteria and
      with use of sensitive laboratory screening tests it is possible to reduce the
      incidence of transfusion transmitted infections (TTI) in Indian scenario.

PMID- 27688538
TI  - Cutaneous Tuberculosis : A Clinico-morphological Study.
AB  - BACKGROUND: Cutaneous tuberculosis forms a small subset of extrapulmonary
      tuberculosis. The present study is an attempt to observe the clinico
      morphological pattern seen in cases of cutaneous tuberculosis over a period of 5
      years, and to correlate them with mantoux reactivity and human immunodeficiency
      virus (HIV) status. METHODS: All cases of cutaneous tuberculosis observed among
      the dermatology in patients and those attending out patient department were
      included in the study. The basis of diagnosis was clinical, histopathological and
      microbiological. Intradermal mantoux test and serological test in the form of
      enzyme-linked immunosorbent assay (ELISA) for tuberculosis was done. HIV
      screening was carried out in 32 cases. CD4 counts were done in all HIV positive
      cases. RESULTS: A total 0.02% patient attending the dermatology centre had
      cutaneous tuberculosis. The spectrum of infection included 19 (51%) cases of
      lupus vulgaris, 7 (19%) cases of papulonecrotic tuberculids, six cases each of
      tuberculosis verrucosa cutis and scrofuloderma. One case had scrofuloderma and
      lupus vulgaris and another both scrofuloderma and papulonecrotic tuberculide. One
      case of lichen scrofulosorum was seen in a seven year old boy. 11 cases revealed
      evidence of systemic tuberculosis. Seven cases of HIV with CD4 counts between 50
      500 cells/MUl were observed in this study.

PMID- 27688540
TI  - Medical Abortion-An Alternative to Surgical Abortion.
AB  - BACKGROUND: Termination of early pregnancy has traditionally been done
      surgically, but agents are now available which can terminate pregnancy if taken
      orally, vaginally or parenterally. We have used a combination of mifepristone and
      misoprostol for termination of early pregnancy. MATERIAL AND METHOD: Fifty
      patients having amenorrhoea of upto 56 days with confirmed intrauterine
      pregnancy, were selected for medical termination of pregnancy. The patients were
      given tablet mifepristone (200mg) on day 1 and tablet misoprostol (400mcg) on day
      3. On day 14, an ultrasound was done to confirm complete abortion. RESULT:
      Majority 35 (70%) patients had amenorrhoea between 40 - 50 days. The duration of
      bleeding was less than 5 days in 12%, between 5 -10 days in 56%, 10 -13 days in
      16% and greater than 14 days in 16%. In all patients with bleeding of more than
      14 days ultrasonography confirmed intrauterine products & a suction evacuation
      was done. In this series there were no failures. CONCLUSION: The combination of
      mifepristone and misoprostol is an effective method for termination of early
      pregnancy up to 56 days of amenorrhoea.

PMID- 27688541
TI  - Efficacy of Nebulised Epinephrine versus Salbutamol in Hospitalised Children with
      Bronchiolitis.
AB  - BACKGROUND: The use of bronchodilators in bronchiolitis lacks consensus. The
      efficacy of nebulised epinephrine versus salbutamol in bronchiolitis and the
      safety profile of the bronchodilators was studied. METHODS: Effects of nebulised
      epinephrine and salbutamol were compared in children with moderate to severe
      acute bronchiolitis. Thirty children between 2 to 24 months of age were
      recruited, 15 in each treatment group. Children received periodic (0,30,60
      minutes followed by 4 hourly) doses of either 1:1000 laevo- epinephrine (0.5ml/kg
      subject to a maximum of 2.5ml with 3ml saline) or salbutamol (0.15mg/kg with 3ml
      saline) via nebuliser with oxygen. Changes in heart rate (HR), respiratory rate
      (RR), respiratory distress assessment instrument (RDAI), oxygen saturation
      (SpO2), oxygen requirement, duration of hospital stay and the side effects were
      studied. RESULTS: The respiratory status was better with significant improvement
      in RR, RDAI score and SpO2, decreased oxygen requirement and shorter hospital
      stay in the epinephrine group. There were no significant side effects in either
      group. CONCLUSION: Nebulised epinephrine is a useful and safe drug for
      moderate/severe bronchiolitis and is superior to salbutamol.

PMID- 27688542
TI  - Lymphatic Filariasis in India : Problems, Challenges and New Initiatives.
AB  - Filariasis is a major public health problem in India and inspite of existence of
      the National Filaria Control Programme since 1955, currently there may be up to
      31 million microfilaraemics, 23 million cases of symptomatic filariasis, and
      about 473 million individuals potentially at risk of infection. Over the last 10
      years advances have led to new diagnostic/ treatment tools and control strategies
      for filariasis. The new control strategy aims at transmission control through
      mass treatment and at disease control through individual patient management. As a
      signatory to 50(th) World Health Assembly resolution on global elimination of
      lymphatic filariasis in 1997, revised filariasis control program was launched in
      India in 13 districts in seven endemic states where mass drug administration was
      undertaken. Single dose mass administration annually in combination with other
      techniques has already eliminated lymphatic filariasis from Japan, Taiwan, South
      Korea and Solomon Islands and markedly reduced the transmission in China. Very
      high treatment coverage (probably > 85%) is required to achieve interruption of
      transmission and elimination in India. Hence, there is an urgent need for
      effective drug delivery strategies that are adapted to regional differences. This
      requires powerful advocacy tools and strategies as well as procedures for
      monitoring and evaluating the impact of elimination programme. 

PMID- 27688543
TI  - Problems in Diagnosis of HIV Infection in Babies.
AB  - Serological diagnosis of human immunodeficiency virus (HIV) infection in babies
      born to HIV infected mothers is difficult because of presence of maternal anti
      HIV antibody up to 18 months. Conventional enzyme-linked immunosorbent assay
      (ELISA) and western blot may be positive in un-infected cases. Various other
      modalities which have been adopted include detection of HIV specific IgA, IgM,
      IgE, detection of p24 antigen, viral culture and detection of HIV nucleic acid by
      polymerase chain reaction (PCR). Viral culture or PCR positivity within first 48
      hours of life indicates intrauterine infection. An early diagnosis of HIV
      infection in babies born to HIV infected mothers is essential as definite
      antiretroviral therapy (ART) can be instituted and unnecessary toxicity of drug
      therapy avoided if found negative. Though viral culture and DNA-PCR has
      sensitivity of >95% after one month of age, some cases can not be diagnosed
      during this period. Other tests like viral RNA detection by reverse transcription
      polymerase chain reaction (RT-PCR) and combination of tests will be required. 

PMID- 27688544
TI  - Partner Counselling and Referral Services (PCRS) for HIV in Armed Forces -
      Visiting a Blind Spot.
AB  - The Indian armed forces have over 5000 cases of human immunodeficiency virus
      (HIV) infection since 1990. The spouses of the affected soldiers are at a
      constant risk of contracting infection if not informed of their husband's HIV
      status. The onus of counselling the spouse has been delegated to the commanding
      officer (CO) of the soldier as per policy. The spouses usually reside at their
      hometown away from the soldier's unit and bridging this "geographical
      discordance" and offering effective counselling becomes a tricky issue for the
      commanding officer (CO). This article examines the effectiveness of this strategy
      as practised in Indian armed forces. 

PMID- 27688545
TI  - Ultrasound Guided Central Venous Cannulation.

PMID- 27688546
TI  - HELLP Syndrome : Report of Two Cases.

PMID- 27688547
TI  - Cutaneous Sarcoidosis: Report of Two Cases.

PMID- 27688548
TI  - Bronchiolitis Obliterans with Organising Pneumonia presenting as Non Resolving
      Pneumonia.

PMID- 27688549
TI  - Association of a Tourette-like Syndrome with Sparfloxacin.

PMID- 27688550
TI  - Pathological Laughter, Multiple Sclerosis, Behavioural Abnormality.

PMID- 27688552
TI  - Tropical Pyomyositis : Rare Presentation.

PMID- 27688551
TI  - Mammary Tuberculosis - A Case Report.

PMID- 27688553
TI  - Hepatitis A : An Unusual Presentation.

PMID- 27688554
TI  - Malaria - the Master Masquerader.

PMID- 27688555
TI  - An Unusual Presentation of Lepromatous Leprosy.

PMID- 27688556
TI  - Pneumomediastinum - An Uncommon Complication of Acute Severe Asthma.

PMID- 27688557
TI  - Social Rehabilitation of HIV/AIDS Orphans.

PMID- 27688559
TI  - Prevalence of Haemolysis in Peripheral Blood Smear in Cases of Megaloblastic
      Anemia.

PMID- 27688560
TI  - Medication Error - Learning From It.

PMID- 27688561
TI  - Vision 2020: Right to Sight - India.

PMID- 27688562
TI  - Effects of Low Dose Vasopressin in Catecholamine Resistant Septic Shock.
AB  - BACKGROUND: Septic shock commonly leads to death in critically ill patients.
      Severe hypotension resistant to conventional catecholamine leads to multiorgan
      failure. We studied the effectiveness of low dose vasopressin in resistant septic
      shock. METHODS: Thirty critically ill patients with catecholamine resistant
      hypotension were included in the study. After adequate fluid resuscitation,
      infusion of norepinephrine and dobutamine was started. If the patient remained
      hypotensive, vasopressin was infused at a fixed rate of 0.04 unit/minute for 24
      hours. Haemodynamic parameters and mortality rates were recorded. RESULT: There
      was a significant improvement in systolic and mean arterial pressure within four
      hours of starting vasopressin. This improvement continued throughout the 24-hour
      period. In addition, it was possible to withdraw dopamine in all the patients and
      significantly reduce infusion rates of dobutamine and norepinephrine. No
      significant complication was noted. CONCLUSION: Low dose vasopressin at the rate
      of 0.04 unit/minute is an effective vasopressor in adult patients with
      catecholamine resistant septic shock.

PMID- 27688563
TI  - Awake Craniotomy for Tumour Excision.
AB  - BACKGROUND: Craniotomy and excision of tumours can produce neurological deficits
      if the tumour is located close to eloquent areas of the brain. One technique of
      overcoming this problem is to keep the patient 'awake' during surgery. METHODS:
      Eight patients with intra cranial space occupying lesions (ICSOL) were operated
      'awake', using a combination of skull block with sedation and analgesia. A
      mixture of 0.125% bupivacaine and 0.5% lignocaine was used for various nerve and
      field blocks. Midazolam, fentanyl and propofol in titrated doses were used to
      achieve conscious sedation. RESULT: The procedure was successful in all the
      patients. They tolerated the procedure well and were able to follow the commands
      intraoperatively as desired. There were no significant complications. CONCLUSION:
      Awake craniotomy with skull blocks with sedation and analgesia is a well
      established procedure. It requires a good rapport between surgeon,
      anaesthesiologist and the patient.

PMID- 27688564
TI  - Spectrum of Haemoglobinopathies in a Tertiary Care Hospital of Armed Forces.
AB  - BACKGROUND: Thalassaemia and other structural haemoglobinopathies are the major
      genetic disorders prevalent in certain parts of the world including India. This
      study presents the pattern of haemoglobinopathies amongst the referred patients
      of anaemia in a two-year period. METHODS: A total of 1032 patients were studied
      during a two-year period for anaemia investigation. Haematological indices,
      sickling test and haemoglobin electrophoresis with quantification of the bands
      was done in all cases. RESULT: Out of 1032 cases, 774 (75%) were normal and 258
      (25%) cases had abnormal haemoglobin pattern. Of the 258 abnormal cases, 136
      (53%) were males and 122 (47%) were females. Of all cases of anaemia 370 (36%)
      were microcytic hypochromic, 237 (23%) macrocytic, 151 (15%) were dimorphic and
      the rest (26%) had normocytic normochromic picture. 82% of microcytic hypochromic
      anaemias had reduced serum iron and elevated total iron binding capacity (TIBC),
      whereas 85% had decreased serum ferritin levels. Spectrum of haemoglobinopathies
      prevalent were beta-Thalassemia trait (17%), followed by sickle cell trait
      (2.3%). Other haemoglobinopathies in descending order of frequency were sickle
      cell disease (1.7%), Hb D trait (1%), Hb E trait (0.8%), sickle cell - beta
      thalassemia, Hb E disease, E - beta thalassemia (0.6% each) and thalassemia major
      (0.4%). CONCLUSION: This study provides a comprehensive database on the spectrum
      of haemoglobinopathies in the Armed Forces. It is suggested that detection of
      HbA2 should be carried out in all the high-risk groups with anaemia.

PMID- 27688565
TI  - Management of Nucleus and IOL Drop.
AB  - BACKGROUND: Thirty six cases of lenticular nucleus drop following
      phacoemulsification and 43 cases of posterior dislocation of intraocular lens
      (IOL) inclusive of two paediatric cases were managed by a modified vitrectomy
      procedure without using perfluorocarbon liquid (PFCL). METHODS: In these cases
      the incision was placed inferotemporally at pars plana. The limbal sites of the
      earlier cataract surgery were utilised as the other two ports. In either case
      adequate vitrectomy was performed first. In cases of nuclear drop, the nucleus
      was impaled (speared) with a micro vitreo retinal blade and brought into the
      anterior chamber from where it was delivered out. In cases of IOL drop the same
      was picked up by an intra-vitreal forceps. RESULT: Of the 77 adult cases treated
      57 (74%) of the eyes had a visual recovery of 6/18 or more. CONCLUSION: Prompt
      surgical management in cases of nuclear drop or posterior dislocation of IOL
      yields good results.

PMID- 27688566
TI  - Risk Factors for Coronary Artery Disease in Indians.
AB  - BACKGROUND: A case control study was carried out to study the emerging risk
      factors for coronary artery disease in Indians. METHODS: The diagnosis of
      coronary artery disease was based on correlation of clinical, biochemical,
      electrocardiography, echocardiography, treadmill testing and coronary
      arteriography findings. The study comprised 100 cases of coronary artery disease
      (acute coronary syndrome and chronic coronary artery disease) and 100 controls in
      two tertiary care service hospitals. The subjects were evaluated for total plasma
      homocysteine, insulin, C-reactive protein (CRP), lipoprotein fibrinogen and anti
      chlamydial anti-bodies. RESULT: Male to female ratio was 10:1 in study group with
      similar predominance of males in controls. Mean age of the cases was 47 years
      (range 25-59 years) and that of controls was 43 years (range 23-56 years). 64%
      cases had acute coronary syndrome and 34% had chronic coronary artery disease. In
      the coronary artery disease population, 76% cases had hyperhomocyteinemia, 9%
      hyperinsulinaemia, 11% abnormal CRP values, 23% abnormal lipoprotein (a) levels,
      40% IgG anti-chlamydial anti-bodies and only 11% had Ig M anti-chlamydial
      antibodies. In the control population, 72% had hyperhomocystinaemia and 6%
      hyperinsulinaemia while 23% and 9% controls had IgG and IgM anti chlamydial
      antibodies respectively. In control group 19% cases had abnormal lipoprotein(a)
      levels and only 2% had abnormal C reactive protein values. Significant
      correlation of CAD was seen with CRP values and Ig G anti-chlamydial antibodies.
      Both the study group and controls had higher homocysteine levels than that
      observed in some Indian and Western studies. CONCLUSION: High C reactive protein
      levels and Ig G anti-chlamydial antibodies are associated with coronary artery
      disease in Indians. Insulin, lipoprotein A, fibrinogen, lgM anti-chlamydial
      antibodies and higher levels of total plasma homocysteine have no significant
      association with coronary artery disease.

PMID- 27688567
TI  - Use of Anti-Craving Agents in Soldiers with Alcohol Dependence Syndrome.
AB  - BACKGROUND: In a search for an effective 'anti-alcohol pill', three modern anti
      craving agents have been studied in alcoholics of Army/ DSC, Air Force, Navy and
      Coast Guard. METHODS: 129 patients of alcohol dependence syndrome were randomly
      assigned to three groups where topiramate, acamprosate and naltrexone were used
      as anti-craving agents in a year long prospective study. Of these 92 patients
      completed the study. RESULT AND CONCLUSION: Topiramate (76.3%) appears to be
      significantly more effective (p<0.01) in sustaining abstinence, though naltrexone
      (57.7%) and acamprosate (60.70%) offer moderate relapse-prevention efficacy. Side
      effects of all the three agents have been mild, transient and self-limiting. We
      recommend a trial of topiramate, before invaliding out of any alcoholic soldier.

PMID- 27688568
TI  - Comparative Study of Recovery after Sevoflurane versus Halothane Anaesthesia in
      Adult Patients.
AB  - BACKGROUND: Induction and maintenance characteristics of sevoflurane and
      halothane have been studied, but little work has been done to compare the
      postoperative recovery of these two agents. METHODS: Sixty adult, ASA I and II
      patients were allocated randomly into Group A and Group B of 30 each. Group A
      received sevoflurane and Group B received halothane for maintenance. At the end
      of surgery early recovery, intermediate recovery and discharge criteria were
      assessed. RESULTS: Early recovery assessed with the mean time to extubation was
      6.7 +/- 2.29 min in Group A and 9.07 +/- 1.64 min in Group B; eye opening was
      7.28 +/- 2.3 min in Group A and 10.6 +/- 1.77 min in Group B; response to verbal
      command was 8.52 +/- 2.83 min in Group A and 12.33 +/- 2.17 min in Group B, while
      orientation was 10.43 +/- 3.15 min in Group A and 14.77 +/- 2.66 min in Group B.
      These differences were statistically significant (p<0.001). The mean time to
      reach post anaesthesia care unit discharge criteria was shorter for Group A (21.1
      +/- 4.69 min) as compared to Group B (27.43 +/- 6.51 min) and this difference was
      statistically significant (p<0.001). CONCLUSION: Early recovery time and time
      taken to achieve discharge criteria were faster with sevoflurane.

PMID- 27688569
TI  - Antibody to Hepatitis B Surface Antigen in Vaccinated Health Care Workers.
AB  - BACKGROUND: Health care workers (HCWs) in Armed Forces are immunised against
      Hepatitis B virus (HBV), however they are not subjected to anti-HBs (antibody to
      Hepatitis B surface antigen) assessment after primary vaccination. The present
      study was undertaken to determine the protection offered by HBV vaccine in HCW.
      METHODS: Cross-sectional study was carried out at tertiary care hospital. A total
      146 HBV vaccine compliant HCW were evaluated for quantitative anti-HBs by enzyme
      immune assay. RESULT: 129 (88.4%) subjects had protective levels of anti-HBs.
      Higher age at vaccination was an important risk factor in low vaccine response.
      Decline in anti-HBs with time was evident. Anti-HBs levels were more than
      10mIU/ml in subjects even after 11 years of primary vaccination. There was no
      difference in protection in booster and non booster groups. CONCLUSION: Age is
      the most important factor in HBV vaccine response. Booster dose of HBV vaccine is
      not necessary in healthy HCW for atleast ten years after primary vaccination. The
      study recommends early primary vaccination of HCW and 'initial' anti-HBs assay
      for confirmation of vaccine response.

PMID- 27688571
TI  - Conjunctival-Limbal Autograft for Primary and Recurrent Pterygium.
AB  - BACKGROUND: It has been postulated that pterygium results from hypo function of
      limbal stem cells. Therefore conjunctival-limbal autograft has been advocated for
      the treatment of this condition. This study was undertaken to evaluate the
      results of conjunctival-limbal autograft procedure in primary and recurrent
      pterygia. METHODS: 32 eyes of 28 individuals with primary and recurrent pterygium
      (24 primary, 8 recurrent) were undertaken for conjunctival-limbal autograft
      procedure under peribulbar anaesthesia followed by topical antibiotic- steroid
      drops for two weeks. The cases were reviewed as per protocol for 6 to 18 months.
      RESULT: There was no recurrence of pterygium in these cases and they were free
      from any major postoperative complications. CONCLUSION: Conjunctival-limbal
      autograft is the procedure of choice for primary and recurrent pterygia.

PMID- 27688570
TI  - Dengue: A Clinicohaematological Profile.
AB  - BACKGROUND: Fifty cases of fever, clinically suspected to be dengue were studied.
      METHODS: Complete clinical, haematological evaluation and IgM capture assay was
      done. RESULT: 54% of patients clinically suspected to have dengue were positive
      for IgM antibodies by enzyme-linked immunosorbent assay (ELISA). The commonest
      clinical feature was fever with rash (85%). Thrombocytopenia was seen in 19% of
      patients only. One patient died of dengue shock syndrome (DSS). CONCLUSION: Out
      of the 27 cases of seropositive dengue there was one death due to dengue shock
      syndrome. Thrombocytopenia may not always be a feature of dengue.

PMID- 27688572
TI  - Chlamydia trachomatis Infection and Photosensitive Dermatoses.
AB  - BACKGROUND: Photosensitivity to Chlamydia trachomatis has been described in
      almost 50% of chronic cases of lymphogranuloma venereum (LGV) caused by L1, L2 or
      L3 serovars. Photosensitivity in non LGV strains of C trachomatis has not been
      studied. We studied the association of various photosensitive dermatoses with C
      trachomatis infection in non LGV cases. METHODS: Sera of all the cases of
      photosensitivity, melasma, chronic actinic dermatitis (CAD), polymorphic light
      eruption (PLE), actinic prurigo (AP) and rosacea were tested for the presence of
      IgM, IgG and IgA antibodies to C trachomatis by ELISA method. The results were
      compared with 30 healthy controls. RESULT: Seventeen (25.53%) of 57 cases of
      photosensitivity as against two (6.67%) controls were seropositive for
      IgM/IgG/IgA antibodies, a statistically significant difference (chi(2) 6.18, p
      0.013). Similarly, significantly higher seropositivity was observed in 12
      (25.53%) of 47 cases of melasma (chi(2) 4.38, p 0.0363) and six (46.15%) of 13
      cases with CAD (chi(2) 6.91, p 0.0086). Although higher proportion of patients of
      rosacea [five (31.25%) of 16 cases] and PLE [four (25.0%) of 16 cases] were
      seropositive, the difference was not statistically significant (chi(2) 3.23, p
      >0.05, OR 6.36, CI 95% 0 to 48 and chi(2) 3.09, p 0.078, OR 4.67, CI 95% 5 to 41
      respectively). There was no association of AP. CONCLUSION: The observations
      suggest that C trachomatis infection in non LGV cases is an important cause of
      PS, melasma and CAD. It appears to be an important cause of rosacea and PLE. We
      recommend that all cases of photosensitivity, melasma, CAD, PMLE and rosacea and
      their spouses/sexual contacts be investigated for C trachomatis infection.

PMID- 27688573
TI  - Cholestasis of Pregnancy : A Prospective Study.
AB  - BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) typically occurs during
      the last trimester of gestation. The most accurate marker for diagnosis and
      follow-up of ICP is increased total bile acid levels (above 11.0 micro mol/L)
      [1]. ICP is a benign disease with no consequences to the mother but it is
      associated with an increased rate of fetal morbidity and mortality. METHOD: A
      prospective study was carried out in 1500 deliveries which included 27 cases of
      ICP. The mode of delivery, complications and fetal outcome of intrahepatic
      cholestasis group were compared with rest of the deliveries. Cases having
      pruritic lesions of skin, viral hepatitis, gall stones, autoimmune liver diseases
      were excluded. Random selection of 300 pregnancies in the control group was done
      and their liver function tests were carried out for comparison. All the patients
      with cholestasis of pregnancy were treated with ursodeoxycholic acid. RESULT: The
      levels of the aminotransferases and alkaline phosphatase levels rose
      significantly (p < 0.05) in the study group. Cholestatic group did not have any
      significant difference in mode of delivery or fetal outcome from the control
      group. The patients in the study group were treated with ursodeoxycholic acid
      with significant relief in symptoms (p < 0.01), while improvement in serum
      bilirubin levels, alkaline phosphatase levels and aminotransferases levels were
      not statistically significant. CONCLUSION: In absence of serum bile acids levels,
      alkaline phosphatase and aminotransferases levels may help in diagnosis and
      management of cholestasis of pregnancy. Ursodeoxycholic acid treatment is
      effective in reducing the pruritus.

PMID- 27688574
TI  - Accidental Outbreak of Non-Bacterial Food Poisoning.
AB  - BACKGROUND: Troops deployed in isolated garrisons face erratic supply of rations.
      At times they resort to use of locally grown plants without knowledge of local
      flora, resulting in accidental food poisoning. METHODS: This is a descriptive,
      analytical and epidemiological study of one such outbreak of food poisoning, due
      to use of a locally grown plant as vegetable, amongst soldiers of a unit in high
      altitude. An epidemiological case sheet was made and food specific attack rates
      of those exposed and not exposed were calculated to identify the food item. The
      toxicological analysis of food item established the cause. RESULTS: Of the 39
      people who consumed the meal, 29 fell ill with an attack rate of 74.35%. All the
      cases presented with classical features of atropine poisoning and were managed
      with sedatives, physostigmine and supportive care. Twenty one had symptoms severe
      enough to warrant hospitalization. All the cases made complete recovery. The
      attack rate for food item containing plant poison was 96.4%. The toxicological
      analysis of food sample established the presence of atropine alkaloids. The plant
      was identified on flowering as Atropa acuminata. CONCLUSION: An outbreak of non
      bacterial food poisoning in soldiers at high altitude, caused by accidental
      ingestion of a dish made out of Atropa acuminata plant leaves containing atropine
      related alkaloids was investigated and conclusively established.

PMID- 27688575
TI  - Body Mass Index and Obesity : Tailoring "cut-off" for an Asian Indian Male
      Population.
AB  - BACKGROUND: Obesity/overweight is a recognized risk factor for a host of
      disorders. The disease risk stratification is commonly based on the Quetelets
      Index (Body Mass Index- BMI), a surrogate measure of fatness. The currently used
      BMI cut-offs to classify people as overweight or obese in Armed Forces have been
      defined in studies on Caucasian populations. However, because of differences in
      body structure and composition in different ethnic, socioeconomic, cultural and
      regional groups the correspondence between BMI and body fat content varies
      between populations. We conducted this pilot study in the Indian Navy to define
      BMI cut-offs for overweight and obesity using body fat content derived from Skin
      Fold Thickness as the standard. MATERIAL AND METHODS: The study was conducted on
      121 volunteers from a naval hospital staff in the age range of 18 to 47 years.
      The mean age, height, weight, BMI, body fat in the study group was 26.73 years
      (+/- 5.5098), 168.56 cm (+/- 6.1034), 65.92 Kg (+/- 10.2746), 23.17 Kg/m(2) (+/-
      3.0265) and 19.91% (+/- 4.831) respectively. RESULTS: The prevalence of
      overweight/obesity was 20.66% by BMI and 47.11% by body fat content. Receiver
      operating characteristic (ROC) curve analysis defined a BMI of 23.85 kg/m(2) as
      the cut off for overweight with a sensitivity of 70.2% (95% CI 56.6 - 81.6) and
      87.5% specificity (95% CI 76.8-94.4) and a BMI of 24.38 kg/m(2)with 90%
      sensitivity (95% CI 68.3-98.5) and 81.2% specificity (95% CI 72.2-88.3) for
      obesity. CONCLUSION: The results of our study suggest lower BMI cut offs for
      overweight and obesity in Indian populations than those recommended by WHO.

PMID- 27688576
TI  - Cerebral Venous Thrombosis.

PMID- 27688577
TI  - Racecadotril : A Novel Antidiarrheal.

PMID- 27688578
TI  - Mobile Phones - Ban or Boon?

PMID- 27688579
TI  - Acute Respiratory Distress Syndrome due to Vivax Malaria.

PMID- 27688581
TI  - Gaucher Disease in Two Siblings.

PMID- 27688580
TI  - Spontaneous Pneumomediastinum in a Case of Mixed Connective Tissue Disorder.

PMID- 27688582
TI  - Transfusion in Blood Group A2B with Anti A1 Recipient.

PMID- 27688583
TI  - Sternoclavicular Tuberculosis.

PMID- 27688584
TI  - Flash Pulmonary Oedema following Prostodin in Pregnancy.

PMID- 27688585
TI  - Computed Tomography of Brain in Polycythemia.

PMID- 27688586
TI  - Best's Vitelliform Macular Dystrophy.

PMID- 27688587
TI  - Dentigerous Cyst of Mandible with Multiple Complex Odontomes.

PMID- 27688588
TI  - Peripheral Osteoma of Mandible.

PMID- 27688589
TI  - Reattachment of Crown Fragment for Immediate Esthetics.

PMID- 27688590
TI  - Abruptio Placentae Leading to Fetal Death and Adult Respiratory Distress
      Syndrome.

PMID- 27688591
TI  - Outcomes of keratoplasty in the mucopolysaccharidoses: an international
      perspective.
AB  - OBJECTIVE: To describe visual outcomes after penetrating keratoplasty and deep
      anterior lamellar keratoplasty in patients with mucopolysaccharidoses. METHODS:
      This is a retrospective review of keratoplasty in consecutive patients from
      Brazil, England, Finland, Germany, Portugal, Sweden and the USA. All patients had
      corneal clouding due to mucopolysaccharidoses. Preoperative and postoperative
      visual outcome and ocular comorbidities were identified. Success was arbitrarily
      defined as any improvement in visual acuity or best-corrected visual acuity
      better than logarithm of the minimum angle of resolution 0.30 (20/40).
      Statistical analysis included only data from first operated eyes in the 16
      patients who underwent bilateral keratoplasty. RESULTS: Forty-eight eyes from 32
      patients with mucopolysaccharidoses I, IV or VI are reported. Mean follow-up was
      70 months (range: 5-186). Penetrating keratoplasty was performed in 45 eyes and
      deep anterior lamellar keratoplasty in 3 eyes. At last follow-up, a successful
      visual outcome for penetrating keratoplasty in first operated/only operated eyes
      was found in 63%. Rejection episodes occurred in 23% of grafts; however, a clear
      graft was recorded at last follow-up in 94%. Ocular pathway comorbidities were
      identified in 63% of eyes transplanted. CONCLUSIONS: Clear corneal grafts can be
      obtained for patients with corneal clouding due to mucopolysaccharidosis with
      improvement in visual acuity in the majority.

PMID- 27688592
TI  - Release of experimental retinal vein occlusions by direct intraluminal injection
      of ocriplasmin.
AB  - PURPOSE: Retinal vein occlusions (RVO) are a major cause of vision loss in people
      aged 50 years and older. Current therapeutic options limit the consequences of
      RVO but do not eliminate the cause. Cannulation of the involved vessel and
      removal of the clot may provide a more permanent solution with a less demanding
      follow-up. However, cannulation of smaller retinal veins remains challenging.
      This paper explores the use of ocriplasmin (recombinant plasmin without its
      kringles) to clear RVO, using a robotic micromanipulator. METHODS: Branch RVO
      were induced in a porcine model with rose bengal followed by 532 nm endolaser to
      the superior venous branch of the optic nerve. The vein was cannulated proximal
      to the occlusion or beyond the first branching vessel from the obstruction. The
      vein was infused with a physiologic citric acid buffer solution (CAM) or
      CAM/ocriplasmin. The time of cannulation, number of attempts, and the ability to
      release the thrombus were recorded. RESULTS: Cannulation and infusion was
      possible in all the cases. The use of a micromanipulator allowed for a consistent
      cannulation of the retinal vein and positional stability allowed the vein to
      remain cannulated for up to 20 min. In none of the attempts (5/5) with CAM did
      the thrombus dissolve, despite repeat infusion/relaxation cycles. In 7/7
      injections of CAM/ocriplasmin near to the point of obstruction, the clot started
      to dissolve within a few minutes of injection. An infusion, attempted beyond the
      first venous branch point proximal to the clot, was unsuccessful in 2/3 attempts.
      CONCLUSIONS: Ocriplasmin is effective in resolving RVO if injected close to the
      site of occlusion with the use of a micromanipulator.

PMID- 27688593
TI  - Characteristics and variations of in vivo Schlemm's canal and collector channel
      microstructures in enhanced-depth imaging optical coherence tomography.
AB  - BACKGROUND/AIMS: To characterise in vivo Schlemm's canal (SC) and collector
      channels (CC) microstructures using enhanced-depth imaging (EDI) optical
      coherence tomography (OCT). METHODS: Serial horizontal EDI OCT B-scans (81 scans,
      15*5 degrees  rectangle) were prospectively obtained in the nasal and temporal
      limbus. SC cross-sectional area (CSA) was measured by delineating its lumen in
      each B-scan. CCs connected to SC were counted. SC CSA and the number of CCs were
      compared between the nasal and temporal areas. RESULTS: Eleven eyes (11 normal
      subjects) were included (mean age, 28+/-5 years). SC and CCs were clearly
      demarcated in EDI OCT B-scans with excellent repeatability and reproducibility
      (intraclass correlation coefficients, 0.830-0.886 and 0.793, respectively; all
      p<0.001). SC CSA varied considerably among subjects, ranging from 1664 to 6007
      um2 (average, 3514+/-1235 um2), and among different regions of the same eye with
      coefficient of variation in each eye ranging from 23% to 46% (average, 32+/-7%).
      The number of CCs in the analysed area also varied considerably among subjects,
      ranging from 5 to 11 (average, 8.73+/-1.85). The mean SC CSA (3839+/-1402 um2 vs
      3189+/-1209 um2; p=0.033) and number of CCs (5.5+/-1.4 vs 3.3+/-1.1; p=0.001)
      were significantly greater nasally than temporally. The mean SC CSA was
      significantly correlated with the number of CCs (r=0.635, p=0.036). CONCLUSIONS:
      High-quality images of the aqueous outflow pathway can be obtained with a
      clinical device, avoiding postacquisition processing. In vivo SC and CC
      microstructures vary considerably among individuals and regions. SC tends to be
      larger in regions with more CCs.

PMID- 27688594
TI  - The P1 biomarker for assessing cortical maturation in pediatric hearing loss: a
      review.
AB  - We review evidence for a high degree of neuroplasticity of the central auditory
      pathways in early childhood, citing evidence of studies of the P1 and N1 cortical
      auditory evoked potentials in congenitally deaf children receiving cochlear
      implants at different ages during childhood, children with auditory neuropathy
      spectrum disorder and children with hearing loss and comorbid multiple
      disabilities. We discuss neuroplasticity, including cortico-cortical de-coupling
      and cross-modal re-organization that occurs in deafness. We provide evidence for
      the clinical utility of the P1 cortical auditory evoked potential (CAEP) as a non
      invasive biomarker that can be used to objectively assess maturation of auditory
      cortex in clinical cases of cochlear implant patients and candidates. Finally, we
      present clinical case studies in which the P1 CAEP biomarker proved useful in
      clinical decision-making regarding intervention in cases of single-sided
      deafness, auditory neuropathy spectrum disorder, mild hearing loss and
      hypoplastic auditory nerve.

PMID- 27688595
TI  - Finding a Life Worth Living: Meaning in Life and Graduation from College.
AB  - Graduation from college is an important milestone for young adults, marked by
      mixed emotions and poignancy, and therefore is an especially salient context for
      studying meaning in life. The present research used experience-sampling
      methodology to examine the antecedents and consequences of students' experience
      of meaning in life over the course of graduation. Participants were 74 graduating
      students who provided a total of 538 reports over the span of three days,
      including commencement day. Increased levels of state meaning in life during the
      days around commencement were linked to spending time with people in general and
      with family in particular, as well as thinking about one's years in college.
      Thinking about one's years in college mediated the effects of present company on
      state meaning in life. Graduates who experienced higher levels of state meaning
      in life during the days around their commencement ceremony had higher trait
      levels of meaning in life one week following commencement. We discuss how making
      meaning of a poignant experience has implications for healthy psychological
      development.

PMID- 27688596
TI  - A Biomass Flow Approach to Population Models and Food Webs.
AB  - The dominant differential equation paradigm for modeling the population dynamics
      of species interacting in the framework of a food web retains at its core the
      basic prey-predator and competition models formulation by Alfred J. Lotka (1880
      1945) and Vito Volterra (1860-1940) nearly nine decades ago. This paradigm lacks
      a trophic-level-independent formulation of population growth leading to
      ambiguities in how to treat populations that are simultaneously both prey and
      predator. Also, this paradigm does not fundamentally include inertial (i.e.
      change resisting) processes needed to account for the response of populations to
      fluctuating resource environments. Here I present an approach that corrects both
      these deficits and provides a unified framework for accounting for biomass
      transformation in food webs that include both live and dead components of all
      species in the system. This biomass transformation formulation (BTW) allows for a
      unified treatment of webs that include consumers of both live and dead material
      both carnivores and carcasivores, herbivores and detritivores-and incorporates
      scavengers, parasites, and other neglected food web consumption categories in a
      coherent manner. I trace how BTW is an outgrowth of the metaphysiological growth
      modeling paradigm and I provide a general compact formulation of BTW in terms of
      a three-variable differential equation formulation for each species in the food
      web: viz. live biomass, dead biomass, and a food-intake-related measure called
      deficit-stress. I then illustrate the application of this new paradigm to provide
      insights into two-species competition in variable environments and discuss
      application of BTW to food webs that incorporate parasites and pathogens.

PMID- 27688598
TI  - Radiological images are shadows of reality.

PMID- 27688597
TI  - Dictionary Pruning with Visual Word Significance for Medical Image Retrieval.
AB  - Content-based medical image retrieval (CBMIR) is an active research area for
      disease diagnosis and treatment but it can be problematic given the small visual
      variations between anatomical structures. We propose a retrieval method based on
      a bag-of-visual-words (BoVW) to identify discriminative characteristics between
      different medical images with Pruned Dictionary based on Latent Semantic Topic
      description. We refer to this as the PD-LST retrieval. Our method has two main
      components. First, we calculate a topic-word significance value for each visual
      word given a certain latent topic to evaluate how the word is connected to this
      latent topic. The latent topics are learnt, based on the relationship between the
      images and words, and are employed to bridge the gap between low-level visual
      features and high-level semantics. These latent topics describe the images and
      words semantically and can thus facilitate more meaningful comparisons between
      the words. Second, we compute an overall-word significance value to evaluate the
      significance of a visual word within the entire dictionary. We designed an
      iterative ranking method to measure overall-word significance by considering the
      relationship between all latent topics and words. The words with higher values
      are considered meaningful with more significant discriminative power in
      differentiating medical images. We evaluated our method on two public medical
      imaging datasets and it showed improved retrieval accuracy and efficiency.

PMID- 27688599
TI  - Cognitive Impairment Involving Social Cognition in SPG4 Hereditary Spastic
      Paraplegia.
AB  - Objectives. To describe cognitive assessment including social cognition in SPG4
      patients. Methods. We reported a series of nine patients with SPG4 mutation with
      an extensive neuropsychological examination including social cognition
      assessment. Results. None of our patients presented with mental retardation or
      dementia. All presented with mild cognitive impairment with a high frequency of
      attention deficit (100%), executive disorders (89%), and social cognition
      impairment (78%). An asymptomatic patient for motor skills presented with the
      same cognitive profile. No correlation was found in this small sample between
      cognitive impairment and motor impairment, age at disease onset, or disease
      duration. Conclusions. SPG4 phenotypes share some cognitive features of
      frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cognitive
      disorders including executive disorders and social cognition impairment are
      frequent in SPG4 patients and might sometimes occur before motor disorders.
      Therefore, cognitive functions including social cognition should be
      systematically assessed in order to improve the clinical management of this
      population.

PMID- 27688600
TI  - Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines
      and Chemokine Receptors in Cardiac Tissue from Chronic Trypanosoma cruzi-Infected
      Dogs.
AB  - Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into
      cardiac tissue infected by the Trypanosoma cruzi. This study investigated the
      long-term treatment with subantimicrobial doses of doxycycline (Dox) in
      association, or not, with benznidazole (Bz) on the expression of CK and CKR in
      cardiac tissue. Thirty mongrel dogs were infected, or not, with the Berenice-78
      strain of T. cruzi and grouped according their treatments: (i) two months after
      infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months after infection,
      Bz (3,5 mg/kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle. After 14
      months of infection, hearts were excised and processed for qPCR analysis of Th1
      (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL11), Th2 (CCL1, CCL17, CCL24, and CCL26),
      Th17 (CCL20) CKs, Th1 (CCR5, CCR6, and CXCR3), and Th2/Th17 (CCR3, CCR4, and
      CCR8) CKR, as well as IL-17. T. cruzi infection increases CCL1, CCL2, CCL4, CCL5,
      CCL17, CXCL10, and CCR5 expression in the heart. Dox, Bz, or Dox + Bz treatments
      cause a reversal of CK and CKR and reduce the expression of CCL20, IL-17, CCR6,
      and CXCR3. Our data reveal an immune modulatory effect of Dox with Bz, during the
      chronic phase of infection suggesting a promising therapy for cardiac protection.

PMID- 27688601
TI  - Prospective Clinical Trial for Septic Arthritis: Cartilage Degradation and
      Inflammation Are Associated with Upregulation of Cartilage Metabolites.
AB  - Background. Intra-articular infections can rapidly lead to osteoarthritic
      degradation. The aim of this clinical biomarker analysis was to investigate the
      influence of inflammation on cartilage destruction and metabolism. Methods.
      Patients with acute joint infections were enrolled in a prospective clinical
      trial and the cytokine composition of effusions (n = 76) was analyzed.
      Characteristics of epidemiology and disease severity were correlated with levels
      of cytokines with known roles in cartilage turnover and degradation. Results.
      Higher synovial IL-1beta concentrations were associated with clinical parameters
      indicating a higher disease severity (p < 0.03) excluding the incidence of
      sepsis. Additionally, intra-articular IL-1beta levels correlated with
      inflammatory serum parameters as leucocyte counts (LC) and C-reactive protein
      concentrations (p < 0.05) but not with age or comorbidity. Both higher LC and
      synovial IL-1beta levels were associated with increased intra-articular collagen
      type II cleavage products (C2C) indicating cartilage degradation. Joints with
      preinfectious lesions had higher C2C levels. Intra-articular inflammation led to
      increased concentrations of typical cartilage metabolites as bFGF, BMP-2, and BMP
      7. Infections with Staphylococcus species induced higher IL-1beta expression but
      less cartilage destruction than other bacteria. Conclusion. Articular infections
      have bacteria-specific implications on cartilage metabolism. Collagen type II
      cleavage products reliably mark destruction, which is associated with
      upregulation of typical cartilage turnover cytokines. This trial is registered
      with DRKS00003536, MISSinG.

PMID- 27688602
TI  - SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting
      Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage
      Migration.
AB  - Nicotine, a major chemical component of cigarettes, plays a pivotal role in the
      development of abdominal aortic aneurysm (AAA). c-Jun N-terminal kinase (JNK) has
      been demonstrated to participate in elastase-induced AAA. This study aimed to
      elucidate whether the JNK inhibitor SP600125 can attenuate nicotine plus
      angiotensin II- (AngII-) induced AAA formation and to assess the underlying
      molecular mechanisms. SP600125 significantly attenuated nicotine plus AngII
      induced AAA formation. The expression of matrix metalloproteinase- (MMP-) 2, MMP
      9, monocyte chemoattractant protein- (MCP-) 1, and regulated-on-activation,
      normal T-cells expressed and secreted (RANTES) was significantly upregulated in
      aortic aneurysm lesions but inhibited by SP600125. In vitro, nicotine induced the
      expression of MCP-1 and RANTES in both RAW264.7 (mouse macrophage) and MOVAS
      (mouse vascular smooth muscle) cells in a dose-dependent manner; expression was
      upregulated by 0.5 ng/mL nicotine but strongly downregulated by 500 ng/mL
      nicotine. SP600125 attenuated the upregulation of MCP-1 and RANTES expression and
      subsequent macrophage migration. In conclusion, SP600125 attenuates nicotine plus
      AngII-induced AAA formation likely by inhibiting MMP-2, MMP-9, MCP-1, and RANTES.
      The expression of chemokines in MOVAS cells induced by nicotine has an effect on
      RAW264.7 migration, which is likely to contribute to the development of nicotine
      related AAA.

PMID- 27688604
TI  - Efficacy and safety of eribulin mesylate in advanced soft tissue sarcomas.
AB  - Despite recent advances in the field, treatment options for metastatic soft
      tissue sarcoma patients are limited. Eribulin, an antimitotic derived from the
      natural marine sponge product halichondrin B, is currently approved for the
      treatment of metastatic breast cancer. Following the promising activity of
      eribulin in sarcoma in a Phase II trial, the drug was recently compared to
      dacarbazine in pretreated advanced leiomyosarcoma (LMS) and liposarcoma (LPS)
      patients in a Phase III trial. Eribulin was associated with a significant 2-month
      improvement in median overall survival compared to dacarbazine (13.5 vs. 11.5
      months, heart rate: 0.768) despite no documented significant difference in
      progression-free survival. In a subgroup analysis, the survival advantage
      associated with eribulin was evident in the LPS subgroup but not in the LMS
      subgroup. Following these encouraging results, the Food and Drug Administration
      has approved eribulin for the treatment of advanced LPS for patients who received
      prior anthracycline chemotherapy. In this short review, we will evaluate the
      evidence for eribulin in soft tissue sarcoma, highlight its mechanisms of action,
      and summarize the results of the major preclinical and clinical studies with a
      particular focus on the results of the Phase III trial. 

PMID- 27688605
TI  - PET/CT in paediatric malignancies - An update.
AB  - (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well
      established imaging modality in adult oncological practice. Its role in childhood
      malignancies needs to be discussed as paediatric malignancies differ from adults
      in tumor subtypes and they have different tumor biology and FDG uptake patterns.
      This is also compounded by smaller body mass, dosimetric restrictions, and
      physiological factors that can affect the FDG uptake. It calls for careful
      planning of the PET study, preparing the child, the parents, and expertise of
      nuclear physicians in reporting pediatric positron emission tomography/computed
      tomography (PET/CT) studies. In a broad perspective, FDG-PET/CT has been used in
      staging, assessment of therapy response, identifying metastases and as a follow
      up tool in a wide variety of pediatric malignancies. This review outlines the
      role of PET/CT in childhood malignancies other than hematological malignancies
      such as lymphoma and leukemia. 

PMID- 27688603
TI  - Anti-Inflammation of Natural Components from Medicinal Plants at Low
      Concentrations in Brain via Inhibiting Neutrophil Infiltration after Stroke.
AB  - Inflammation after stroke consists of activation of microglia/astrocytes in situ
      and infiltration of blood-borne leukocytes, resulting in brain damage and
      neurological deficits. Mounting data demonstrated that most natural components
      from medicinal plants had anti-inflammatory effects after ischemic stroke through
      inhibiting activation of resident microglia/astrocytes within ischemic area.
      However, it is speculated that this classical activity cannot account for the
      anti-inflammatory function of these natural components in the cerebral
      parenchyma, where they are detected at very low concentrations due to their poor
      membrane permeability and slight leakage of BBB. Could these drugs exert anti
      inflammatory effects peripherally without being delivered across the BBB?
      Factually, ameliorating blood-borne neutrophil recruitment in peripheral
      circulatory system has been proved to reduce ischemic damage and improve
      outcomes. Thus, it is concluded that if drugs could achieve effective
      concentrations in the cerebral parenchyma, they can function via crippling
      resident microglia/astrocytes activation and inhibiting neutrophil infiltration,
      whereas the latter will be dominating when these drugs localize in the brain at a
      low concentration. In this review, the availability of some natural components
      crossing the BBB in stroke will be discussed, and how these drugs lead to
      improvements in stroke through inhibition of neutrophil rolling, adhesion, and
      transmigration will be illustrated.

PMID- 27688606
TI  - HIV-associated hematologic malignancies: Experience from a Tertiary Cancer Center
      in India.
AB  - CONTEXT AND AIM: Data on HIV associated hematologic malignancies is sparse from
      India. This study attempts to analyze the spectrum and features of this disease
      at a tertiary cancer center in India. SETTING AND METHODS: Retrospective study
      from case records of patients registered with a diagnosis of hematologic
      malignancy and HIV infection between January 2010 and June 2015. RESULTS:
      Thirteen cases of HIV associated hematologic malignancies were identified, six of
      them pediatric. HIV diagnosis was concurrent to diagnosis of cancer in 12 and
      preceded it in one of them. ECOG PS at presentation was >1 in all of them. All
      patients, except one, had B symptoms. Six of the patients had bulky disease and
      six are stage 4. Predominant extranodal disease was seen in 67% of them. NHL
      accounted for 10 of 13 patients and DLBCL-Germinal center was the most common
      subtype. Mean CD4+ cell count was 235/MUL (range, 32-494). HAART could be given
      along with chemotherapy to 11 patients. Two-thirds of patients received standard
      doses of therapy. Chemo-toxicity required hospitalization in 58%. CR was achieved
      in 45% and 36% had progressive disease with first-line therapy. At the time of
      last follow up, 3 patients were alive with responsive disease, 2 in CR and 1 in
      PR. None of the pediatric patients were long time responders. CONCLUSIONS: These
      malignancies were of advanced stage and higher grade. Goal of therapy, in the
      HAART era, is curative. Pediatric patients had dismal outcome despite good
      chemotherapy and HAART. There is an urgent need to improve data collection for
      HIV related cancers in India.

PMID- 27688607
TI  - Plasma Epstein-Barr virus and Hepatitis B virus in non-Hodgkin lymphomas: Two
      lymphotropic, potentially oncogenic, latently occurring DNA viruses.
AB  - CONTEXT: There is a need to study potential infective etiologies in lymphomas.
      Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal
      cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to
      be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And
      recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been
      emphasized. AIMS: The aim of this study was to elucidate the association of two
      potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non
      HL (NHL). SETTINGS AND DESIGN: In this prospective study, we estimated plasma EBV
      and HBV DNA in NHL patients. MATERIALS AND METHODS: Peripheral blood was obtained
      from newly diagnosed, treatment na ive, histologically confirmed NHL patients.
      Plasma EBV DNA was quantified by real-time polymerase chain reaction (PCR)
      targeting Epstein-Barr Nucleic acid 1 while the plasma HBV DNA was detected using
      nested PCR targeting HBX gene. In a small subset of patients, follow-up plasma
      samples post-anticancer chemotherapy were available and retested for viral DNA.
      RESULTS: Of the 110 NHL patients, ~79% were B-cell NHL and ~21% were T-cell NHL.
      Plasma EBV-DNA was detected in 10% NHLs with a higher EBV association in Burkitt
      lymphoma (33.3%) than other subtypes. Pretherapy HBV DNA was detected in 21%
      NHLs; most of them being diffuse large B-cell lymphoma (DLBCL). Moreover, 42% of
      DLBCL patients had HBV DNA in plasma. Since all patients were HBV surface antigen
      seronegative at diagnosis, baseline plasma HBV-DNAemia before chemotherapy was
      indicative of occult hepatitis B infection. CONCLUSIONS: Our findings indicate a
      significant association of HBV with newly diagnosed DLBCL.

PMID- 27688608
TI  - Tobacco-related cancers in India: A review of incidence reported from population
      based cancer registries.
AB  - BACKGROUND: Tobacco related cancers (TRC) account for major share of all cancers
      and updated of incidence data are helpful in policy changes. The aim was to
      present an update of TRCs on age-adjusted incidence data and corresponding
      lifetime risk of developing TRC for different regions of the country. METHODS:
      The data for this study were obtained from published reports of 25 population
      based cancer registries (PBCRs) in India. The PBCRs in different parts of India
      were divided into seven regions such as North, South, Central, Northeast, West,
      Rural West, and East. Data indicators such as age-adjusted rates (AARs) of
      incidence and the cumulative risks of TRCs up to the age of 64 years for each of
      the 10 TRC sites of either sex in each of 25 registries were obtained from the
      National Cancer Registry Programme reports. RESULTS: Among all TRCs, esophagus,
      lung, hypopharynx, and mouth are the leading sites for both males and females.
      Males in Northeast region had the highest risk 1 in 27 of developing esophageal
      cancer, 1 in 67 for cancer of lungs and hypopharynx, followed by 1 in 143 for
      both mouth and tongue cancers. Females also had the highest risk of esophagus and
      lungs (1 in 63 female) and cancer of mouth (1 in 250) in Northeast region.
      Proportion of TRC in comparison of all cancer ranged from 11-25% for men and 3
      18% for women. CONCLUSIONS: Proportion of TRC in relation to all cancers was
      still high in different registries of India including the Northeast region.

PMID- 27688609
TI  - Evaluation of myeloid cells (tumor-associated tissue eosinophils and mast cells)
      infiltration in different grades of oral squamous cell carcinoma.
AB  - BACKGROUND: The multifunctional involvement and infiltration of myeloid cells
      (tumor-associated tissue eosinophils [TATE] and mast cells) can provide a unique
      opportunity to define relevant effectors functions that may represent novel,
      therapeutic options for modulation of tumor onset/growth. AIM: Our study aimed to
      evaluate infiltration of myeloid cells (TATE and Mast cells) infiltration in
      different grades (WHO grading) of oral squamous cell carcinoma (OSCC). MATERIALS
      AND METHODS: Total 30 cases of OSCC were selected for this study. Hematoxylin and
      eosin stain and toluidine blue special stain, to evaluate TATE and the mast cells
      infiltration, were used. Three-year follow-up of OSCC cases was done. RESULT:
      Among 30 cases, 63.33% cases of OSCC showed TATE-positive and 36.66% cases showed
      TATE-negative. Regarding mast cells infiltration, 66.66% OSCC cases showed mast
      cells positive and 33.33% cases did not show significant mast cells infiltration.
      We found significant association of TATE and mast cells infiltration in OSCC
      cases. These myeloid cells infiltration significantly associated with age of
      patients but did not show any significant association with gender, site, and
      habit of cases. When we compared these cells infiltration with clinical stages
      and different histological grades of tumor, we found their infiltration is
      decreasing, from Stages 1 to Stage 3 of tumor and from well to poorly
      differentiated carcinoma. We have also found the less infiltration of these
      myeloid in recurrence cases of OSCC. CONCLUSION: As the infiltration of TATE and
      mast cells are correlated, along with evaluation of TATE, we should also evaluate
      the presence of mast cells infiltration in OSCC. The assessment of myeloid cells
      could become, in the future, useful for therapeutic approaches in this subset of
      the patient.

PMID- 27688611
TI  - Bloodstream infections in febrile neutropenic patients at a tertiary cancer
      institute in South India: A timeline of clinical and microbial trends through the
      years.
AB  - INTRODUCTION: Febrile neutropenia (FN) is an oncological emergency. The choice of
      empiric therapy depends on the locally prevalent pathogens and their
      sensitivities, the sites of infection, and cost. The Infectious Diseases Society
      of America guidelines are being followed for the management of FN in India.
      METHODS: This is a prospective observational study conducted at a tertiary care
      cancer centre from September 2012 to September 2014. OBJECTIVES: The objectives
      of this study were as follows: (1) To review the pattern of microbial flora,
      susceptibility pattern, and important clinical variables among bloodstream
      infections in febrile neutropenic patients with solid tumors and hematological
      malignancies. (2) As per the institutional protocol to periodically review the
      antibiotic policy and susceptibility pattern, and compare the findings with an
      earlier study done in our institute in 2010. This was a prospective study
      conducted from September 2012 to September 2014. RESULTS: About 379 episodes of
      FN were documented among 300 patients. About 887 blood cultures were drawn. Of
      these, 137 (15%) isolates were cultured. Isolates having identical antibiograms
      obtained from a single patient during the same hospitalization were considered as
      one. Hence, 128 isolates were analyzed. About 74 (58%) cultures yielded Gram
      negative bacilli, 51 (40%) were positive for Gram-positive cocci, and 3 (2%) grew
      fungi. Among Gram-negative organisms, Escherichia coli followed by Acinetobacter
      baumannii and Klebsiella pneumoniae accounted for 78% of the isolates. Among Gram
      positive cocci, Staphylococcus species accounted for 84% of the isolates. We have
      noted a changing trend in the antibiotic sensitivity pattern over the years.
      Following the switch in empirical antibiotics, based on the results of the study
      done in 2010 (when the empirical antibiotics were ceftazidime + amikacin), the
      sensitivity to cefoperazone-sulbactam has plunged from about 80% to 60%%. Similar
      reduction in susceptibility was noted for piperacillin-tazobactam, imipenem, and
      meropenem. On the contrary, there was a marked increase in sensitivity to
      ceftazidime (50-76%). Based on these results, we have reverted to ceftazidime +
      amikacin as the empirical antibiotics. CONCLUSION: Every institute must have a
      regular revision of antibiotic policy based on periodic assessment of the
      clinical and microbiological profile in FN. This will combat antibiotic
      resistance.

PMID- 27688610
TI  - Newly established stem cell transplant program: 100 days follow-up of patients
      and its comparison with published Indian literature.
AB  - BACKGROUND: Hematopoietic progenitor stem cell transplantation (HPSCT) is used as
      a standard treatment option to improve outcome in hematological and
      nonhematological disorders. It is important for new HPSCT program to look at its
      patient outcome data and compare it with the published data to evaluate the
      efficacy of program. AIMS: The aim was to compile and collate the patient outcome
      data of HPSCT and compare with published reports. MATERIALS AND METHODS: Patient
      demographics, indications, stem cell harvest by apheresis, dose collected,
      infusion, engraftment, and follow-up data were collected from hospital
      information system from 2010 to 2013 in a tertiary care hospital. HPSCs were
      mobilized with granulocyte colony-stimulating factor, and harvests were done on
      the 5(th) day. Engraftment was decided for neutrophil when counts were 0.5 *
      10(9)/L and for platelets when counts were 20 * 10(9)/L on two consecutive days
      without any transfusion support. RESULTS: There were 133 harvests for 95 patients
      with various disorders; multiple myeloma was most common in autologous and acute
      lymphoblastic leukemia in allogeneic group. One hundred harvests were done for
      autologous and 33 for allogeneic HPSCT. In autologous group, of 66 patients, 60
      (90.9%) received stem cell infusion at median dose of 4.63 * 10(6) CD34(+)
      cells/kg. Similarly, in allogeneic group, of 29 patients, 27 (93.10%) received
      infusion at median dose of 5.8 * 10(6) CD34(+) cells/kg. 58 (96.9%) patients and
      25 (92.6%) engrafted in autologous and allogeneic group, respectively. The median
      time for neutrophils engraftment was 11 days in autologous group and 12 days in
      allogeneic group. The median time for platelet engraftment was 11.5 days in
      autologous group and 13 days in allogeneic group. The 100-day survival rate was
      95% (n = 57) in autologous group and 77.8% (n = 21) in allogeneic group.
      CONCLUSION: This data analysis shows reasonably good results of HPSCTs with
      majority of patients surviving at 100-day follow-up.

PMID- 27688612
TI  - Quantification of telomerase activity in normal oral mucosal tissue and oral
      squamous cell carcinoma.
AB  - BACKGROUND AND OBJECTIVE: The role of telomeres and telomerase in oral cancer is
      an area of much recent interest. The understanding of the role of telomere
      biology, the end replication problem leading to genomic instability and the
      reactivation of telomerase, is absolutely critical to our understanding of oral
      cancer, and more so, to our ability of early diagnosis and developing novel
      therapies and cancer prevention approaches. The aim of the present study was to
      quantify telomerase activity (TA) in oral squamous cell carcinoma (OSCC) and
      normal oral mucosa and assess the role of telomerase as diagnostic and prognostic
      marker of oral malignancy. MATERIALS AND METHODS: We quantified TA in 45 patients
      with OSCC and 20 normal oral mucosal specimens using polymerase chain reaction
      based telomeric repeat amplification protocol assay and compared it with the
      clinical status and grade of malignancy. RESULTS: TA was detected in 89% of
      malignant and 5% of normal oral mucosal tissue. The TA levels ranged from 0.28 to
      6.91 (mean 2.05, standard deviation [SD] 1.33) in OSCC and 0.21 to 1.09 (mean
      0.54, SD 0.27) in normal oral mucosa. There was no relationship between TA levels
      and clinical stages, site of the lesion, history of adverse habits, or sex of the
      patient. However, under the WHO classification, there were significant
      differences (P < 0.00) between Grades I, II, and III. Furthermore, increasing age
      of the patient significantly correlated with TA. INTERPRETATION AND CONCLUSION:
      The results of the present study indicate that activation of TA is frequent in
      OSCC. Statistically significant difference in quantified telomerase levels of
      OSCC and normal oral mucosa (P < 0.00) demonstrates the significant clinical
      usefulness of telomerase activation as a valuable marker for diagnosis while
      significant correlation of TA with grades of malignancy indicates its
      effectiveness as marker for prognosis of OSCC.

PMID- 27688614
TI  - Intrathecal trastuzumab for leptomeningeal carcinomatosis in patients with human
      epidermal growth factor receptor 2 positive breast cancer.
AB  - There has been recent increase in incidence of leptomeningeal carcinomatosis,
      possibly due to widespread use of adjuvant trastuzumab and its known poor CNS
      penetration. Currently there are limited therapeutic options for these patients
      and outcome is poor. We report two cases of women with HER2 positive breast
      cancer who developed leptomeningeal carcinomatosis for which they were treated
      with intrathecal trastuzumab in combination with systemic therapy. Both patients
      had rapid symptomatic benefit and radiological response and remained progression
      free for at least seven months. Intrathecal trastuzumab can be considered a
      reasonable therapeutic option for these difficult to treat patients. 

PMID- 27688613
TI  - Epidermal growth factor receptor mutation in adenocarcinoma lung in a North
      Indian population: Prevalence and relation with different clinical variables.
AB  - INTRODUCTION: Lung cancer is one of the most common causes of cancer deaths
      worldwide. Adenocarcinoma is taking over squamous cell lung cancer as the
      predominant histological subtype. Several cytotoxic drugs are available for the
      treatment of lung cancer, but side effects limit their use. Recently, targeted
      therapies for cancers have come into clinical practice. AIMS AND OBJECTIVES: To
      determine the prevalence of epidermal growth factor receptor (EGFR) mutation in
      adenocarcinoma lung in a North Indian population and its relation with different
      clinical variables. MATERIALS AND METHODS: A total of 57 patients who met
      inclusion criteria were recruited into the study. Relevant history, clinical
      examination and investigations were done. EGFR mutation was done in all patients.
      RESULTS: A total of twenty patients tested positive for EGFR mutation. EGFR was
      more frequently detected in female patients (53.8%), while as only 19.4% of the
      male patients expressed EGFR mutation, which was statistically very significant
      (P = 0.007). EGFR mutation was more frequently detected in nonsmokers (52%) as
      compared to smokers (21.9%) which also was statistically significant (P value of
      0.018). EGFR mutation was more common in Stage III and IV adenocarcinomas (48%)
      as compared to Stage I and II (21.4%) which was statistically significant (P
      value 0.034). CONCLUSION: EGFR mutation should be routinely done in all patients
      of adenocarcinoma lung particularly non-smoker females with Stage III and IV
      disease.

PMID- 27688615
TI  - Isolated humeral recurrence in endometrial carcinoma.
AB  - Isolated skeletal metastasis in endometrial carcinoma at recurrence is very rare.
      We report a 52-year-old woman diagnosed to have FIGO Stage 1b, Grade 1
      endometrioid adenocarcinoma, presenting with isolated distal humerus metastasis,
      2 years after surgery and adjuvant radiotherapy for primary disease. Imaging,
      bone scintigraphy, and cytology confirmed the diagnosis of poorly differentiated
      metastatic adenocarcinoma. She was treated with local radiotherapy followed by
      six cycles of paclitaxel and carboplatin chemotherapy along with zoledronic acid,
      monthly. She is symptom-free after the treatment and at a first follow-up visit
      after 3 months. 

PMID- 27688616
TI  - Early integration of palliative medicine into emergency care: Is it a feasible
      option.
AB  - Patients with advanced malignancy often experience symptoms of disease and
      treatment that contribute to distress and diminish their quality of life. Most of
      these patients present to the emergency department thus raising its importance in
      providing such care especially at the end of life situation. An approach that is
      aimed at controlling these symptoms, whether or not undergoing curative therapy,
      is a key feature of high-quality patient-centered care. This paper explores the
      potential role of palliative medicine in the emergency room and how early
      integration with emergency care can help improve the quality of life of patients
      and thus achieve better outcomes. 

PMID- 27688617
TI  - Neutropenia due to palbociclib: A word of caution?

PMID- 27688618
TI  - Subacute quadriplegic myelopathy following intrathecal methotrexate.

PMID- 27688620
TI  - Developmental Defects Mediated by the P1/HC-Pro Potyviral Silencing Suppressor
      Are Not Due to Misregulation of AUXIN RESPONSE FACTOR 8.
AB  - Plant viral suppressors of RNA silencing induce developmental defects similar to
      those caused by mutations in genes involved in the microRNA pathway. A recent
      report has attributed viral suppressor-mediated developmental defects to up
      regulation of AUXIN RESPONSE FACTOR 8 (ARF8), a target of miR167. The key piece
      of evidence was that the developmental defects in transgenic Arabidopsis
      (Arabidopsis thaliana) expressing viral suppressors were greatly alleviated in
      the F1 progeny of a cross with plants carrying the arf8-6 mutation. Arf8-6 is a
      SALK line T-DNA insertion mutant, a class of mutations prone to inducing
      transcriptional silencing of transgenes expressed from the 35S promoter. We have
      reinvestigated the role of ARF8 in viral suppressor-mediated developmental
      defects, using two independent arf8 mutations and the P1/HC-Pro potyviral
      suppressor of silencing. Progeny of a cross between P1/HC-Pro transgenic
      Arabidopsis and the arf8-6 T-DNA insertion mutant showed little effect on the
      P1/HC-Pro phenotype in the F1 generation, but almost all arf8-6/P1/HC-Pro progeny
      had lost the phenotype in the F2 generation. However, the loss of phenotype in
      the F2 generation was not correlated with the number of functional copies of the
      ARF8 gene. Instead, it reflected transcriptional silencing of the P1/HC-Pro
      transgene, as evidenced by a pronounced decrease in P1/HC-Pro mRNA and the
      appearance of 35S promoter small interfering RNAs. Furthermore, an independent
      loss-of-function point mutation, Arf8-8, had no detectable effects on P1/HC-Pro
      phenotype in either the F1 or F2 generations. Together, these data argue against
      the previously reported role of increased ARF8 expression in developmental
      defects caused by P1/HC-Pro.

PMID- 27688619
TI  - Class II Cytochrome P450 Reductase Governs the Biosynthesis of Alkaloids.
AB  - Expansion of the biosynthesis of plant specialized metabolites notably results
      from the massive recruitment of cytochrome P450s that catalyze multiple types of
      conversion of biosynthetic intermediates. For catalysis, P450s require a two
      electron transfer catalyzed by shared cytochrome P450 oxidoreductases (CPRs),
      making these auxiliary proteins an essential component of specialized metabolism.
      CPR isoforms usually group into two distinct classes with different proposed
      roles, namely involvement in primary and basal specialized metabolisms for class
      I and inducible specialized metabolism for class II. By studying the role of CPRs
      in the biosynthesis of monoterpene indole alkaloids, we provide compelling
      evidence of an operational specialization of CPR isoforms in Catharanthus roseus
      (Madagascar periwinkle). Global analyses of gene expression correlation combined
      with transcript localization in specific leaf tissues and gene-silencing
      experiments of both classes of CPR all point to the strict requirement of class
      II CPRs for monoterpene indole alkaloid biosynthesis with a minimal or null role
      of class I. Direct assays of interaction and reduction of P450s in vitro,
      however, showed that both classes of CPR performed equally well. Such high
      specialization of class II CPRs in planta highlights the evolutionary strategy
      that ensures an efficient reduction of P450s in specialized metabolism.

PMID- 27688621
TI  - Phosphorylation of GENOMES UNCOUPLED 4 Alters Stimulation of Mg Chelatase
      Activity in Angiosperms.
AB  - GENOMES UNCOUPLED 4 (GUN4) is a positive regulator of light-dependent chlorophyll
      biosynthesis. GUN4 activates Mg chelatase (MgCh) that catalyzes the insertion of
      an Mg2+ ion into protoporphyrin IX. We show that Arabidopsis (Arabidopsis
      thaliana) GUN4 is phosphorylated at Ser 264 (S264), the penultimate amino acid
      residue at the C terminus. While GUN4 is preferentially phosphorylated in
      darkness, phosphorylation is reduced upon accumulation of Mg porphyrins.
      Expression of a phosphomimicking GUN4(S264D) results in an incomplete
      complementation of the white gun4-2 null mutant and a chlorotic phenotype
      comparable to gun4 knockdown mutants. Phosphorylated GUN4 has a reduced
      stimulatory effect on MgCh in vitro and in vivo but retains its protein stability
      and tetrapyrrole binding capacity. Analysis of GUN4 found in oxygenic
      photosynthetic organisms reveals the evolution of a C-terminal extension, which
      harbors the phosphorylation site of GUN4 expressed in angiosperms. Homologs of
      GUN4 from Synechocystis and Chlamydomonas lack the conserved phosphorylation site
      found in a C-terminal extension of angiosperm GUN4. Biochemical studies proved
      the importance of the C-terminal extension for MgCh stimulation and inactivation
      of GUN4 by phosphorylation in angiosperms. An additional mechanism regulating
      MgCh activity is proposed. In conjunction with the dark repression of 5
      aminolevulinic acid synthesis, GUN4 phosphorylation minimizes the flow of
      intermediates into the Mg branch of the tetrapyrrole metabolic pathway for
      chlorophyll biosynthesis.

PMID- 27688622
TI  - Circadian Clock and Photoperiodic Flowering in Arabidopsis: CONSTANS Is a Hub for
      Signal Integration.

PMID- 27688624
TI  - Comparison of low- and high-dose recombinant activated factor VII for postcardiac
      surgical bleeding.
AB  - AIM OF THE STUDY: A retrospective observational study to compare safety and
      efficacy of high and low doses of recombinant activated factor VIIa (rFVIIa) in
      severe postcardiac surgical bleeding. PATIENTS AND METHODS: From 2004 to 2014,
      all patients who received rFVIIa for bleeding after cardiac surgery were included
      and arranged in two groups; Group 1: Low dose (40-50 mcg/kg) (n = 98) and Group
      2: High dose (90-120 mcg/kg) (n = 156). RESULTS: There was no significant
      difference in demographic and surgical characteristics of both groups on
      admission to Cardiac Surgical Intensive Care Unit (CSICU). There was no
      significant difference between the two groups regarding the reduction in chest
      tube bleeding in the first 6 h or the transfusion requirement in the 24 h after
      admission to CSICU. A total of 15 patients (5.9%) had thromboembolic adverse
      events. (Seven (7.1%) patients in Group 1 compared to 8 (5.1%) patients in Group
      2, P = 0.58). There were no significant differences in all-cause mortality at 30
      days (2% in Group 1 vs. 3.2% in Group 2, P = 0.6) and at hospital discharge
      between the two study groups (6.1% in Group 1 vs. 8.3% in Group 2, P = 0.5),
      respectively. There was no significant difference between the two groups
      regarding the need for re-exploration, days on mechanical ventilation, CSICU, or
      hospital stay. CONCLUSION: In this report, Low-dose rFVIIa showed equivalent
      efficacy and safety to high-dose rFVIIa. Further prospective randomized studies
      are needed to confirm these findings.

PMID- 27688625
TI  - Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord
      injury.
AB  - BACKGROUND: Patients with acute traumatic spinal cord injuries (SCIs) exhibit
      factors that, in other populations, have been associated with rhabdomyolysis.
      PURPOSE: The aim of the study is to determine the incidence of rhabdomyolysis in
      patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as
      well as the development of secondary acute kidney injury and associated factors.
      STUDY DESIGN AND SETTING: This was an observational, retrospective study. PATIENT
      SAMPLE: All adult patients admitted to the ICU with acute traumatic SCI who
      presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels
      >500 IU/L. OUTCOME MEASURES: Incidence of rhabdomyolysis and subsequent renal
      dysfunction was calculated. MATERIALS AND METHODS: Data about demographic
      variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI,
      severity scores, and laboratory parameters were obtained from clinical records.
      Multivariate logistic regression was used to identify renal injury risk factors.
      RESULTS: In 2006-2014, 200 patients with acute SCI were admitted to ICU. Of
      these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]:
      44.3%-58.7%). The most typical American Spinal Injury Association classification
      was A (70.3%). The injury severity score was 30.3 +/- 12.1 and sequential organ
      failure assessment (SOFA) score was 5.6 +/- 3.3 points. During their stay, 57
      patients (55.3%; 95% CI: 45.2%-65.4%) presented renal dysfunction (creatinine
      >=1.2 mg/dL). In the multivariate analysis, variables associated with renal
      dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and
      hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024).
      Creatinine was a better predictor of renal dysfunction than the peak CPK value
      during the rhabdomyolysis (area under the receiver operating characteristic
      curve: 0.91 vs. 0.63, respectively). CONCLUSIONS: Rhabdomyolysis is a frequent
      condition in patients with acute traumatic SCI admitted to the ICU, and renal
      dysfunction occurs in half of the cases. Creatinine values should be requested
      starting at the admission while neither the peak CPK values nor the hemodynamic
      SOFA scores could be used to properly discriminate between patients with and
      without renal dysfunction.

PMID- 27688623
TI  - The Nonspecific Lipid Transfer Protein AtLtpI-4 Is Involved in Suberin Formation
      of Arabidopsis thaliana Crown Galls.
AB  - Nonspecific lipid transfer proteins reversibly bind different types of lipid
      molecules in a hydrophobic cavity. They facilitate phospholipid transfer between
      membranes in vitro, play a role in cuticle and possibly in suberin formation, and
      might be involved in plant pathogen defense signaling. This study focuses on the
      role of the lipid transfer protein AtLTPI-4 in crown gall development.
      Arabidopsis (Arabidopsis thaliana) crown gall tumors, which develop upon
      infection with the virulent Agrobacterium tumefaciens strain C58, highly
      expressed AtLTPI-4 Crown galls of the atltpI-4 loss-of-function mutant were much
      smaller compared with those of wild-type plants. The gene expression pattern and
      localization of the protein to the plasma membrane pointed to a function of
      AtLTPI-4 in cell wall suberization. Since Arabidopsis crown galls are covered by
      a suberin-containing periderm instead of a cuticle, we analyzed the suberin
      composition of crown galls and found a reduction in the amounts of long-chain
      fatty acids (C18:0) in the atltpI-4 mutant. To demonstrate the impact of AtLtpI-4
      on extracellular lipid composition, we expressed the protein in Arabidopsis
      epidermis cells. This led to a significant increase in the very-long-chain fatty
      acids C24 and C26 in the cuticular wax fraction. Homology modeling and lipid
      protein-overlay assays showed that AtLtpI-4 protein can bind these very-long
      chain fatty acids. Thus, AtLtpI-4 protein may facilitate the transfer of long
      chain as well as very-long-chain fatty acids into the apoplast, depending on the
      cell type in which it is expressed. In crown galls, which endogenously express
      AtLtpI-4, it is involved in suberin formation.

PMID- 27688626
TI  - Bronchoalveolar lavage fluid cytokine bead array profile for prognostication of
      ventilated trauma patients.
AB  - AIM OF STUDY: Ventilator-associated pneumonia (VAP) is a common cause of
      mortality in trauma patients admitted to Intensive Care Units. The outcome of
      such patients may be dependent on local host immune response, which may be best
      reflected in studies using bronchoalveolar lavage (BAL) fluid. The present study
      was conducted to ascertain the cytokine profile of BAL using the cytometric bead
      array (CBA) in a flow cytometer and to correlate the levels of Th-1/Th-2
      cytokines in BAL with the clinical outcome of ventilated trauma patients.
      PATIENTS AND METHODS: BAL was collected from the patients with suspected VAP. CBA
      was performed to assess the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-1
      beta, interferon gamma (IFN-gamma), and tumor necrosis factor-alpha in the BAL
      samples. After acquiring the BAL samples on the flow cytometer, the results were
      generated using FCAP ArrayTM software. The cytokine profile was correlated to
      clinical outcomes. RESULTS: A total of forty patients were enrolled during the
      study period. Of these, 12 patients (30%) had confirmed VAP and 8 (20%) patients
      had a fatal outcome. The levels of IL-8 and IFN-gamma correlated significantly
      with the development of VAP and elevated IL-6 in BAL was associated with a poor
      outcome. CONCLUSION: A proinflammatory response in the form of elevated IL-6 and
      IL-8 correlated poorly with the clinical outcome. Th-1 response was significantly
      reduced in patients with VAP. A proinflammatory response in the form of elevated
      IL-6 and IL-8 correlated poorly with the clinical outcome.

PMID- 27688627
TI  - Association of serum interleukin-6, interleukin-8, and Acute Physiology and
      Chronic Health Evaluation II score with clinical outcome in patients with acute
      respiratory distress syndrome.
AB  - BACKGROUND AND AIM: Studies on potential biomarkers in experimental models of
      acute lung injury (ALI) and clinical samples from patients with ALI have provided
      evidence to the pathophysiology of the mechanisms of lung injury and predictor of
      clinical outcome. Because of the high mortality and substantial variability in
      outcomes in patients with acute respiratory distress syndrome (ARDS),
      identification of biomarkers such as cytokines is important to determine
      prognosis and guide clinical decision-making. MATERIALS AND METHODS: In this
      study, we have included thirty patients admitted to Intensive Care Unit diagnosed
      with ARDS, and serum samples were collected on day 1 and 7 and were analyzed for
      serum interleukin-6 (IL-6) and IL-8 by ELISA method, and Acute Physiology and
      Chronic Health Evaluation II (APACHE II) scoring was done on day 1. RESULTS: The
      mortality in the patients observed with ARDS was 34%. APACHE II score was
      significantly higher in nonsurvivors as compared to survivors. There were no
      significant differences in gender and biochemical and hematological parameters
      among the survivors and nonsurvivors. Serum IL-6 and IL-8 levels on day 1 were
      significantly higher in all the ARDS patients as compared to healthy controls and
      these levels were returned to near-normal basal levels on day 7. The serum IL-6
      and IL-8 levels measured on day 7 were of survivors. As compared to survivors,
      the IL-6 and IL-8 levels were significantly higher in nonsurvivors measured on
      day 1. Spearman's rank correlation analysis indicated a significant positive
      correlation of APACHE II with IL-8. By using APACHE II score, IL-6, and IL-8, the
      receiver operating characteristic curve was plotted and the provided predictable
      accuracy of mortality (outcome) was 94%. CONCLUSION: The present study
      highlighted the importance of measuring the cytokines such as IL-6 and IL-8 in
      patients with ARDS in predicting the clinical outcome.

PMID- 27688628
TI  - Acute kidney injury in Pediatric Intensive Care Unit: Incidence, risk factors,
      and outcome.
AB  - OBJECTIVE: To determine incidence, risk factors, and outcome of acute kidney
      injury (AKI) in Pediatric Intensive Care Unit (PICU). MATERIALS AND METHODS: This
      is a prospective, observational study conducted in PICU of Department of
      Paediatrics, S.P. Medical College, Bikaner, from October 2013 to May 2014. In
      this study, 536 patients of aged 29 days to 16 years were screened for AKI
      according to the Pediatric Risk, Injury, Failure, Loss, End-stage Renal Disease
      (pRIFLE) criteria. Their clinical and biochemical data were recorded and followed
      up to their discharge/death. RESULTS: During the study period, 230 (42.9%) out of
      536 patients developed AKI. Younger age (<5 years) and females (P <= 0.013) were
      more prone to develop AKI. Most common etiologies were septicemia, multiple organ
      dysfunction syndrome (MODS), gastroenteritis, and severe malaria (P <= 0.05). The
      maximal stage of AKI was stage "R" (49.1%), followed by "I" (29.5%) and "F"
      (21.3%). Major PICU-related risk factors were use of vasoactive drug (VD) and
      nephrotoxic drug (ND) and need of mechanical ventilation (MV) (P <= 0.05). Length
      of stay was significantly longer than non-AKI patients (P <= 0.05). Mortality in
      AKI (47.5%) was higher (P <= 0.05%) in comparison to non-AKI (25.56%).
      CONCLUSION: AKI is common in critically sick children, especially in younger age
      and in females with septicemia and MODS. Use of VD and ND and need of MV are
      common risk factors. AKI is associated with longer hospital stay and higher
      mortality. pRIFLE is better diagnostic criteria in early detection of AKI and
      reduction of their morbidity and mortality.

PMID- 27688629
TI  - Comparative evaluation of the role of single and multiple blood specimens in the
      outcome of blood cultures using BacT/ALERT 3D (automated) blood culture system in
      a tertiary care hospital.
AB  - INTRODUCTION: Bloodstream infection (BSI) is a leading cause of mortality in
      critically ill patients. The mortality directly attributable to BSI has been
      estimated to be around 16% and 40% in general hospital population and Intensive
      Care Unit (ICU) population, respectively. The detection rate of these infections
      increases with the number of blood samples obtained for culture. The newer
      continuous monitoring automated blood culture systems with enhanced culture media
      show increased yield and sensitivity. Hence, we aimed at studying the role of
      single and multiple blood specimens from different sites at the same time in the
      outcome of automated blood culture system. MATERIALS AND METHODS AND RESULTS: A
      total of 1054 blood culture sets were analyzed over 1 year, the sensitivity of
      one, two, and three samples in a set was found to be 85.67%, 96.59%, and 100%,
      respectively, which showed a statistically significant difference (P < 0.0001).
      Similar findings were seen in few more studies, however, among individual
      organisms in contrast to other studies, the isolation rates of Gram-positive
      bacteria were less than that of Gram-negative Bacilli with one (or first) sample
      in a blood culture set. In our study, despite using BacT/ALERT three-dimensional
      continuous culture monitoring system with FAN plus culture bottles, 15% of
      positive cultures would have been missed if only a single sample was collected in
      a blood culture set. CONCLUSION: The variables like the volume of blood and
      number of samples collected from different sites still play a major role in the
      outcome of these automated blood culture systems.

PMID- 27688631
TI  - Diagnosing obstructive shock: Echocardiography is the third eye of a vigilant
      intensivist.
AB  - Training in echocardiography is essential for an intensivist. We present a
      rapidly fatal case of obstructive shock where a vigilant intensivist could
      diagnose left atrial mass obstructing the mitral inflow as the etiology of shock.

PMID- 27688630
TI  - Systematic review of statins in sepsis: There is no evidence of dose response.
AB  - OBJECTIVES: Sepsis is a common cause of morbidity and mortality and is associated
      with significant costs to the healthcare organizations. We performed a systematic
      review and meta-analysis to assess whether high or low-dose statin therapy
      improved mortality in patients with sepsis. METHODS: The trials analyzed in this
      study were multicenter or single center randomized control studies using statins
      for sepsis in a hospital setting. The patients included were adults with
      suspected or confirmed infection. INTERVENTIONS: This study found eight
      randomized controlled trials where participants were given either a statin or
      placebo daily for 14-28 days, the duration of their illness, or until their death
      or discharge, which ever occurred first. PRIMARY AND SECONDARY OUTCOMES MEASURED:
      This meta-analysis measured the effect of statin therapy on in hospital and 28
      days mortality. RESULTS: In unselected patients, there was no demonstrable
      difference in the 28 days mortality (relative risk [RR] 0.88 95% confidence
      interval [CI], 0.70-1.12 and P = 0.16). There was also no significant difference
      between statin versus placebo for in-hospital mortality (RR 0.98 95% CI, 0.85
      1.14 P = 0.36). When the studies where divided into low-dose and high-dose
      groups, there were no statistically significant differences for in-hospital
      mortality between low-dose statin versus placebo for (RR 0.81 CI 0.44-1.49 P =
      0.27) or high-dose statin versus placebo (RR 0.99 95% CI 0.85-1.16, P = 0.28).
      There was no significant difference in adverse effects between the high- and low
      dose groups. CONCLUSIONS: In this meta-analysis, we found that the use of statins
      did not significantly improve either in-hospital mortality or 28-day mortality in
      patients with sepsis. In the low-dose group, there were fewer quality multicenter
      studies; hence, conclusions based on the results of this subgroup are limited.

PMID- 27688632
TI  - Point-of-care ultrasonography of the orbit for detection of retinal detachment in
      a patient with hemolysis, elevated liver enzymes, and low platelet count
      syndrome.
AB  - Retinal detachment is a rare, but well-known cause of visual impairment in
      patients with hemolysis, elevated liver enzymes, and low platelet count (HELLP)
      syndrome. With supportive care, patients usually improve, with complete recovery
      of vision. Bedside ultrasonography of the orbit can be helpful for early
      detection of retinal detachment in these patients. Here, we present a case of
      HELLP syndrome presenting with severe visual symptoms. Retinal detachment was
      detected with point-of-care ocular sonography, which was confirmed with
      ophthalmoscopic examination. The patient was reassured of the favorable
      prognosis. Early initiation of aggressive supportive care was followed by
      progressive improvement of vision, which correlated with sonographic evidence of
      resolution of detachment. Her vision recovered completely in 2 weeks. 

PMID- 27688633
TI  - Lance-Adams syndrome: A special case of a mother.
AB  - Predicting the neurological outcome in survivors of cardiorespiratory arrest is
      difficult. A distinction has been made between acute and chronic posthypoxic
      myoclonus, called myoclonic status epilepticus and Lance-Adams syndrome (LAS),
      respectively, with the acute condition carrying a bad prognosis. Here, we report
      a case of a 37-year-old female who developed seizures after a successful
      cardiopulmonary resuscitation. The available literature on such cases is very
      rare and has generally mentioned a poor outcome. However, our patient was
      successfully managed and showed clinical features of LAS. Thus, making an early
      diagnosis and proper management of hypoxic brain insults is positively related to
      improving the patient's functional outcome. 

PMID- 27688634
TI  - Hantavirus pulmonary syndrome in a postpartum woman.
AB  - Hantavirus infection, a rare disease diagnosed in India and carries a very high
      mortality. There are no reports of this infection in association with pregnancy
      or postpartum period in our country. We present a case of a 30-year-old female
      diagnosed to have hantavirus pulmonary syndrome in the postpartum period. We
      intend to create awareness about this infection and consider it in the
      differential diagnosis of patients presenting with acute respiratory distress
      syndrome and multiorgan dysfunction in association with pregnancy and postpartum
      period. 

PMID- 27688635
TI  - Aseptic handling of ultrasound probe: An easy solution.

PMID- 27688636
TI  - Author's reply to the letter to editor, "Yakson touch as a part of early
      intervention in the Neonatal Intensive Care Unit: A systematic narrative review -
      comment".

PMID- 27688637
TI  - Erratum: Acute intermittent porphyria: A critical diagnosis for favourable
      outcome.
AB  - [This corrects the article on p. 428 in vol. 20, PMID: 27555700.].

PMID- 27688638
TI  - E-learning in orthopedic surgery training: A systematic review.
AB  - E-learning is the use of internet-based resources in education. In the field of
      surgical education, this definition includes the use of virtual patient cases,
      digital modeling, online tutorials, as well as video recordings of surgical
      procedures and lectures. In recent years, e-learning has increasingly been
      considered a viable alternative to traditional teaching within a number of
      surgical fields. Here we present (1) a systematic review of literature assessing
      the efficacy of e-learning modules for orthopedic education and (2) a discussion
      of their relevance. A systematic search of PubMed, Embase, Web of Science, and
      the Cochrane Library was conducted according to the guidelines defined in the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement
      (PRISMA). The search yielded a total of 255 non-duplicate citations that were
      screened using predetermined inclusion/exclusion criteria. A total of 9 full text
      articles met inclusion criteria, which included the use of an objective outcome
      measure to evaluate an orthopedic e-learning module. Six studies assessed
      knowledge using a multiple-choice test and 4 assessed skills using a clinical
      exam. All studies showed positive score improvement pre- to post-intervention,
      and a majority showed greater score improvement than standard teaching methods in
      both knowledge (4/6 studies) and clinical skills (3/4 studies). E-learning
      represents an effective supplement or even alternative to standard teaching
      techniques within orthopedic education for both medical students and residents.
      Future work should focus on validating specific e-learning programs using
      standardized outcome measures and assessing long-term knowledge retention using e
      learning platforms. 

PMID- 27688639
TI  - Translated and annotated version of the 2015-2020 National Mental Health Work
      Plan of the People's Republic of China.
AB  - The following document is a translation of the 2015-2020 National Mental Health
      Work Plan of the People's Republic of China which was issued by the General
      Office of China's State Council on June 4, 2015. The original Chinese version of
      the document is available at the official government website:
      http://www.gov.cn/gongbao/content/2015/content_2883226.htm The translators have
      added annotations at the end of the document that provide background information
      to help contextualize content that may be unclear to readers unfamiliar with
      China and explain their decisions when translating terms that can have multiple
      interpretations. 

PMID- 27688640
TI  - Effect of group cognitive-behavioral therapy on the quality of life and social
      functioning of patients with mild depression.
AB  - BACKGROUND: Several studies of moderate-to-severe depression have shown that
      combined treatment with individual cognitive behavioral therapy (CBT) and
      antidepressant medication is better than either CBT or antidepressants alone.
      Less research has focused on the outcomes of group-CBT and antidepressants in
      persons with mild depression. AIM: Evaluate the effects of group-CBT in
      combination with antidepressants on the quality of life and social functioning of
      outpatients with mild depression. METHODS: We randomized 62 outpatients with mild
      depression into a control group (n=30) that received antidepressant medication
      for 12 weeks and an intervention group (n=32) that received antidepressants and
      group-CBT for 12 weeks; both groups were then continued on antidepressants alone
      for one year. Blinded evaluators used Chinese versions of the Hamilton Depression
      Rating Scale, Hamilton Anxiety Rating Scale, Social Disability Screening
      Schedule, Life Satisfaction Rating, Multidimensional Scale of Perceived Social
      Support, and Short Form Health Survey to assess participants after 12 weeks of
      treatment and at the end of one year of follow-up. RESULTS: Repeated measures
      analysis of variance showed that the depressive and anxiety symptoms of both
      groups improved significantly during treatment and that the improvement was
      greater in the CBT+antidepressant experimental group. Almost all of the social
      functioning, social support, and quality of life measures also showed
      significantly greater improvement in the CBT+antidepressant group than in the
      antidepressant-only group. Moreover, even after adjusting for differences in
      baseline demographic and clinical characteristics and for changes in the severity
      of depression and anxiety over time using an analysis of covariance, the greater
      improvement in the CBT+antidepressant group remained statistically significant
      both after the 12 weeks of group-CBT treatment and one year after the group CBT
      had ended. CONCLUSION: Antidepressants alone or combined treatment with
      antidepressants and group-CBT can effectively improve the social function,
      quality of life, and healthy functioning of individuals with mild depression.
      However, combined treatment with both antidepressants and group CBT is better
      than treatment with antidepressants alone, and these benefits persist for up to
      one year after the CBT sessions have ended.

PMID- 27688641
TI  - Comparison of cognitive flexibility and planning ability in patients with
      obsessive compulsive disorder, patients with obsessive compulsive personality
      disorder, and healthy controls.
AB  - BACKGROUND: Cognitive functioning in individuals with Obsessive Compulsive
      Disorder (OCD) and with Obsessive Compulsive Personality Disorder (OCPD) has not
      been adequately studied. AIM: Examine the cognitive flexibility and planning
      ability of individuals with OCD and OCPD. METHODS: Twenty patients with OCD and
      25 patients with OCPD who had not taken medication in the previous two weeks were
      identified in an outpatient psychology clinic in Tehran, and 25 healthy control
      subjects were identified from the university staff and local community residents.
      All participants were administered the 28-item version of the General Health
      Questionnaire (GHQ-28), the Wisconsin Card Sorting Test (WCST), and the Tower of
      London (TOL) test. Two measures of the WCTS (number of perseverative errors and
      number of categories completed) were used to assess cognitive flexibility and
      three measures of the TOL (total number of moves in 12 trials, total response
      time, and planning time) were used to assess planning ability. RESULTS: The level
      of current psychological distress in the two patient groups was significantly
      greater than that in the control group. After adjusting for demographic variables
      and the level of psychological distress, both OCD patients and OCPD patients made
      more perseverative errors on the WCST than control subjects, and the OCD patients
      (but not the OCPD patients) completed significantly fewer categories than the
      control subjects. Both the OCD patients and OCPD patients required significantly
      more moves than control subjects to complete the 12 TOL tasks and OCD patients
      took significantly longer than both OCPD patients and control subjects to
      complete the tasks. CONCLUSIONS: Individuals with OCD and OCPD have impaired
      cognitive flexibility and planning ability compared to healthy controls, and
      there are some differences in these measures of cognitive functioning between OCD
      and OCPD. Long term follow-up studies of OCD and OCPD that assess changes in
      cognitive measures as the severity of obsessive compulsive symptoms wax and wane
      will be needed to determine whether or not such cognitive measures have
      diagnostic or clinical relevance for obsessive compulsive disorders.

PMID- 27688642
TI  - Cross-sectional study of the severity of self-reported depressive symptoms in
      heroin users who participate in a methadone maintenance treatment program.
AB  - BACKGROUND: Methadone maintenance treatment (MMT) is widely recognized as an
      effective method of combatting narcotic addiction. MMT reduces heroin withdrawal
      symptoms and, thus, makes it possible to provide the psychological and social
      support that is essential to the rehabilitation of drug users. AIM: Compare the
      severity of depressive symptoms in heroin users who are currently receiving MMT
      to that of heroin users who are not receiving MMT. METHODS: We administered the
      13-item version of the Beck Depression Inventory (BDI-13) and a demographic
      history form to 929 heroin users who had been receiving MMT at nine methadone
      treatment clinics in three Chinese cities for an average of 9 months and to 238
      heroin users who had enrolled in a MMT program at the centers but had not yet
      begun MMT. RESULTS: Seventy-nine percent (188/238) of the untreated individuals
      reported depressive symptoms compared to 68% (628/929) of the individuals
      receiving MMT (chi (2)=11.69, p<0.001). The median (interquartile range) BDI
      score in the untreated group was 10.4 (7.9-11.4) compared to 8.0 (5.7-11.6) in
      the MMT group (Z=2.75, p=0.006). In the MMT group, there was a negative
      correlation between the severity of reported depressive symptoms and the duration
      of participation in the MMT program (rs =-0.24, Z=2.88, p=0.004). Multivariate
      linear regression analysis showed that after adjusting for all demographic
      variables the treated group still had less severe depressive symptoms than the
      untreated group. After adjusting for the effect of MMT treatment, depressive
      symptoms were more severe in heroin users who self-reported poor family
      relationships (standardized regression coefficient beta=0.118, t=6.56, p<0.001)
      and in those who were divorced (beta=0.120, t=3.73, p<0.001). CONCLUSIONS:
      Moderate to severe depressive symptoms are common in heroin users. MMT is
      associated with lower levels of depressive symptoms in heroin users, but
      prospective randomized controlled trials are needed to determine whether or not
      MMT actually improves depressive symptoms in heroin users. Poor relationships
      with family members are also associated with depressive symptoms in heroin users;
      this suggests that treatment of heroin addiction needs to incorporate methods for
      helping heroin users repair the severed social relationships that their addiction
      has caused.

PMID- 27688643
TI  - Genetic findings are challenging the symptom-based diagnostic classification
      system of mental disorders.
AB  - The present diagnostic classification of mental illnesses is primarily based on
      symptomatology. A recent cross-disorder genome-wide association study revealed
      that there were genetic similarities between multiple clinically defined
      diagnoses (including schizophrenia, bipolar disorder, depression, attention
      deficit hyperactivity disorder, and autism spectrum disorder) on regions of
      chromosomes 3p21 and 10q24 and single-nucleotide polymorphisms (SNPs) within two
      L-type voltage-gated calcium channel subunits of CACNA1C and CACNB2. These
      findings suggest that the pathogenesis of these five independent disorders are
      related. Such cross-disorder genetic studies challenge the current symptom-based
      diagnostic classification of mental disorders. Researchers need to identify
      creative ways to bridge the gap between these two approaches to understanding and
      labelling mental disorders. 

PMID- 27688644
TI  - Influence of cross-disorder analyses on the diagnostic criteria of mental
      illnesses.
AB  - Cross-disorder studies are identifying shared genetic variations among common
      mental illnesses - including schizophrenia, bipolar disorder, and major
      depression - which are classified as independent disorders in the current
      diagnostic system. These cross-disorder studies are challenging the traditional
      system of diagnosing mental disorders based on clinical symptoms, but it remains
      to be seen whether or not they will lead to an improved method of classifying
      psychiatric disorders that can, in turn, lead to better outcomes for individuals
      suffering from these conditions. 

PMID- 27688645
TI  - Case report of body dysmorphic disorder in a suicidal patient.
AB  - Few reports exist about the treatment of body dysmorphic disorder (BDD) in
      patients who are suicidal. This case report describes a 19-year-old male with BDD
      who had delusional-intensity beliefs about facial disfigurement that had
      gradually intensified over a 2-year period. However, he was initially
      misdiagnosed with depression partly because he was admitted immediately after a
      suicide attempt that was associated with depressive symptoms and social
      withdrawal, symptoms that subsequently proved to be secondary to his BDD. The
      symptoms resolved completely and his social functioning returned to normal after
      8 weeks of inpatient treatment with fluoxetine and cognitive behavioral therapy.
      This report is a reminder that suicidal behavior and ideation can have many
      causes; to avoid misdiagnosis and inappropriate treatment, clinicians should
      consider other possibilities before assuming that suicidal behavior or ideation
      is the direct result of depression. We discuss the many changes in the
      understanding and diagnostic classification of BDD since it was first reported by
      Enrico Morselli in 1886. 

PMID- 27688646
TI  - Case report of a child's anxiety disorder precipitated by tremors from a distant
      earthquake that was extensively covered in local news stories.
AB  - Earthquakes are relatively common natural disasters in many parts of the world,
      but research about the mental health effects of earthquakes remains limited.
      Individuals experiencing an earthquake often suffer significant loss and are at
      increased risk for developing mental disorders. However, the prevalence of mental
      disorders following less dramatic or non-destructive earthquake phenomena is
      unknown. We report the case of a 10-year-old girl who came to a psychiatric
      outpatient department with a 2-week history of severe, disabling anxiety symptoms
      precipitated by non-destructive tremors from a distant earthquake that received
      extensive coverage in the local press. Her condition did not meet criteria for
      any of the specific anxiety-related disorders, so the non-specific DSM-5 category
      'Other Specified Anxiety Disorder' was considered most appropriate. Her symptoms
      resolved over 4 weeks when treated with both a benzodiazepine and a selective
      serotonin reuptake inhibitor. 

PMID- 27688647
TI  - Relationships among three popular measures of differential risks: relative risk,
      risk difference, and odds ratio.
AB  - The relative risk, risk difference, and odds ratio are the three most commonly
      used measures for comparing the risk of disease between different groups.
      Although widely popular in biomedical and psychosocial research, the relationship
      among the three measures has not been clarified in the literature. Many
      researchers incorrectly assume a monotonic relationship, such that higher (or
      lower) values in one measure are associated with higher (or lower) values in the
      other measures. In this paper we discuss three theorems and provide examples
      demonstrating that this is not the case; there is no logical relationship between
      any of these measures. Researchers must be very cautious when implying a
      relationship between the different measures or when combining results of studies
      that use different measures of risk. 

PMID- 27688648
TI  - Segmental colitis associated diverticulosis syndrome.
AB  - Segmental colitis associated diverticulosis (SCAD) has become increasingly
      appreciated as a form of inflammatory disease of the colon. Several features
      suggest that SCAD is a distinct disorder. SCAD tends to develop almost
      exclusively in older adults, predominately, but not exclusively, males. The
      inflammatory process occurs mainly in the sigmoid colon, and usually remains
      localized to this region of the colon alone. SCAD most often presents with rectal
      bleeding and subsequent endoscopic visualization reveals a well localized process
      with non-specific histopathologic inflammatory changes. Granulomas are not seen,
      and if present, may be helpful in definition of other disorders such as Crohn's
      disease of the colon, an entity often confused with SCAD. Bacteriologic and
      parasitic studies for an infectious agent are negative. Normal rectal mucosa
      (i.e., "rectal sparing") is present and can be confirmed with normal rectal
      biopsies. SCAD often resolves spontaneously without treatment, or completely
      after a limited course of therapy with only a 5-aminosalicylate. Recurrent
      episodes may occur, but most often, patients with this disorder have an entirely
      self-limited clinical course. Occasionally, treatment with other agents,
      including corticosteroids, or surgical resection has been required. 

PMID- 27688649
TI  - Guanylyl cyclase C signaling axis and colon cancer prevention.
AB  - Colorectal cancer (CRC) is a major cause of cancer-related mortality and
      morbidity worldwide. While improved treatments have enhanced overall patient
      outcome, disease burden encompassing quality of life, cost of care, and patient
      survival has seen little benefit. Consequently, additional advances in CRC
      treatments remain important, with an emphasis on preventative measures. Guanylyl
      cyclase C (GUCY2C), a transmembrane receptor expressed on intestinal epithelial
      cells, plays an important role in orchestrating intestinal homeostatic
      mechanisms. These effects are mediated by the endogenous hormones guanylin
      (GUCA2A) and uroguanylin (GUCA2B), which bind and activate GUCY2C to regulate
      proliferation, metabolism and barrier function in intestine. Recent studies have
      demonstrated a link between GUCY2C silencing and intestinal dysfunction,
      including tumorigenesis. Indeed, GUCY2C silencing by the near universal loss of
      its paracrine hormone ligands increases colon cancer susceptibility in animals
      and humans. GUCY2C's role as a tumor suppressor has opened the door to a new
      paradigm for CRC prevention by hormone replacement therapy using synthetic
      hormone analogs, such as the FDA-approved oral GUCY2C ligand linaclotide
      (LinzessTM). Here we review the known contributions of the GUCY2C signaling axis
      to CRC, and relate them to a novel clinical strategy targeting tumor
      chemoprevention. 

PMID- 27688651
TI  - Epidemiology of hepatitis C in Greece.
AB  - Hepatitis C is a global health issue and constitutes a major cause of chronic
      liver disease worldwide. In this article, a comprehensive literature search was
      conducted for the prevalence of hepatitis C virus (HCV) infection in Greece,
      since data on the HCV prevalence, viremia and genotypes are important for
      developing strategies to manage or eliminate HCV infection. In addition, the
      pattern of HCV infection was analyzed according to the geographic region and the
      risk factors. These differences reflect not only distinct epidemiological
      characteristics among populations, but also differences on the strategy of data
      acquisition and quantification. Although there are not enough data, the
      estimation of the current prevalence of Hepatitis C in Greece ranges from 0.5% to
      2%. The most important risk factors for HCV infection include blood product
      transfusion, intravenous drug use, chronic hemodialysis, organ transplantation,
      occupational exposure, sexual transmission, and vertical transmission. Because of
      lack of vaccine or effective post-exposure prophylaxis for HCV, the main focus of
      prevention is to recognize and control these risk factors. HCV infection in
      Greece is closely associated with the development of chronic liver disease,
      cirrhosis, and primary hepatocellular carcinoma. As far as the genotype
      distribution is concerned genotype 1 estimated to be 45%-47% and it constitutes
      the prevalent genotype in Greece, followed by genotype 3. 

PMID- 27688650
TI  - Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues,
      and future research directions.
AB  - Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health
      concern. A "multiple-hit" pathogenetic model has been suggested to explain the
      progressive liver damage that occurs among children with NAFLD. In addition to
      the accumulation of fat in the liver, insulin resistance (IR) and oxidative
      stress due to genetic/epigenetic background, unfavorable lifestyles, gut
      microbiota and gut-liver axis dysfunction, and perturbations of trace element
      homeostasis have been shown to be critical for disease progression and the
      development of more severe inflammatory and fibrotic stages [non-alcoholic
      steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age,
      history, anthropometrical data (BMI and waist circumference percentiles), blood
      pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal
      ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow
      a clinician to identify children with obesity and obesity-related conditions,
      including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the
      "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis,
      particularly to exclude other treatable conditions or when advanced liver disease
      is expected on clinical and laboratory grounds and preferably prior to any
      controlled trial of pharmacological/surgical treatments. However, a biopsy
      clearly cannot represent a screening procedure. Advancements in diagnostic serum
      and imaging tools, especially for the non-invasive differentiation between NAFLD
      and NASH, have shown promising results, e.g., magnetic resonance elastography.
      Weight loss and physical activity should be the first option of intervention.
      Effective pharmacological treatments are still under development; however, drugs
      targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut
      microbiota and gut liver axis dysfunction are an option for patients who are
      unable to comply with the recommended lifestyle changes. When morbid obesity
      prevails, bariatric surgery should be considered. 

PMID- 27688652
TI  - How significant is the association between metabolic syndrome and prevalence of
      colorectal neoplasia?
AB  - The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer
      (CRC) has been rising in developed countries. The association between these two
      diseases has been widely studied and reported. Less evidence is available about
      the relationship between MS and CRC precancerous lesions (adenomatous polyps,
      adenomas). The aim of this paper is to present an overview of our scientific
      understanding of that topic and its implication in clinical practice. One of the
      principal goals of current CRC secondary prevention efforts is to detect and
      remove the precancerous lesions in individuals with an average CRC risk to
      prevent the development of invasive cancer. MS is not currently considered a high
      risk CRC factor and is therefore not included in the guidelines of organized
      screening programs. However, in light of growing scientific evidence, the
      approach to patients with MS should be changed. Metabolic risk factors for the
      development of adenomas and cancers are the same - obesity, impaired glucose
      tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes
      mellitus type 2. Therefore, the key issue in the near future is the development
      of a simple scoring system, easy to use in clinical practice, which would
      identify individuals with high metabolic risk of colorectal neoplasia and would
      be used for individual CRC secondary prevention strategies. Currently, such
      scoring systems have been published based on Asian (Asia-Pacific Colorectal
      Screening Score; APCS) and Polish populations. 

PMID- 27688653
TI  - Iron and non-alcoholic fatty liver disease.
AB  - The mechanisms that promote liver injury in non-alcoholic fatty liver disease
      (NAFLD) are yet to be thoroughly elucidated. As such, effective treatment
      strategies are lacking and novel therapeutic targets are required. Iron has been
      widely implicated in the pathogenesis of NAFLD and represents a potential target
      for treatment. Relationships between serum ferritin concentration and NAFLD are
      noted in a majority of studies, although serum ferritin is an imprecise measure
      of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in
      NAFLD have been demonstrated in animal and cell culture models. However, the
      human data linking hepatic iron to liver injury in NAFLD is less clear, with
      seemingly conflicting evidence, supporting either an effect of iron in
      hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a
      key site at which iron may have a pathogenic role in NAFLD. Evidence for this
      comes indirectly from studies that have evaluated the role of adipose tissue iron
      with respect to insulin resistance. Adding further complexity, multiple strands
      of evidence support an effect of NAFLD itself on iron metabolism. In this review,
      we summarise the human and basic science data that has evaluated the role of iron
      in NAFLD pathogenesis. 

PMID- 27688654
TI  - Inflammatory bowel disease in India - Past, present and future.
AB  - There is rising incidence and prevalence of inflammatory bowel disease (IBD) in
      India topping the Southeast Asian (SEA) countries. The common genes implicated in
      disease pathogenesis in the West are not causal in Indian patients and the role
      of "hygiene hypothesis" is unclear. There appears to be a North-South divide with
      more ulcerative colitis (UC) in north and Crohn's disease (CD) in south India.
      IBD in second generation Indian migrants to the West takes the early onset and
      more severe form of the West whereas it retains the nature of its country of
      origin in migrants to SEA countries. The clinical presentation is much like other
      SEA countries (similar age and sex profile, low positive family history and
      effect of smoking, roughly similar disease location, use of aminosalicylates for
      CD, low use of biologics and similar surgical rates) with some differences
      (higher incidence of inflammatory CD, lower perianal disease, higher use of
      aminosalicylates and azathioprine and lower current use of corticosteroids). UC
      presents more with extensive disease not paralleled in severity clinically or
      histologically, follows benign course with easy medical control and low incidence
      of fulminant disease, cancer, complications, and surgery. UC related colorectal
      cancer develop in an unpredictable manner with respect to disease duration and
      site questioning the validity of strict screening protocol. About a third of CD
      patients get antituberculosis drugs and a significant number presents with small
      intestinal bleed which is predominantly afflicted by aggressive inflammation.
      Biomarkers have inadequate diagnostic sensitivity and specificity for both.
      Pediatric IBD tends to be more severe than adult. Population based studies are
      needed to address the lacunae in epidemiology and definition of etiological
      factors. Newer biomarkers and advanced diagnostic techniques (in the field of
      gastrointestinal endoscopy, molecular pathology and genetics) needs to be
      developed for proper disease definition and treatment. 

PMID- 27688657
TI  - Impact of hepatitis B virus infection on hepatic metabolic signaling pathway.
AB  - A growing body of epidemiologic research has demonstrated that metabolic
      derangement exists in patients with hepatitis B virus (HBV) infection, indicating
      that there are clinical associations between HBV infection and host metabolism.
      In order to understand the complex interplay between HBV and hepatic metabolism
      in greater depth, we systematically reviewed these alterations in different
      metabolic signaling pathways due to HBV infection. HBV infection interfered with
      most aspects of hepatic metabolic responses, including glucose, lipid, nucleic
      acid, bile acid and vitamin metabolism. Glucose and lipid metabolism is a
      particular focus due to the significant promotion of gluconeogenesis, glucose
      aerobic oxidation, the pentose phosphate pathway, fatty acid synthesis or
      oxidation, phospholipid and cholesterol biosynthesis affected by HBV. These
      altered metabolic pathways are involved in the pathological process of not only
      hepatitis B, but also metabolic disorders, increasing the occurrence of
      complications, such as hepatocellular carcinoma and liver steatosis. Thus, a
      clearer understanding of the hepatic metabolic pathways affected by HBV and its
      pathogenesis is necessary to develop more novel therapeutic strategies targeting
      viral eradication. 

PMID- 27688656
TI  - Gastrointestinal disorders associated with migraine: A comprehensive review.
AB  - Migraine is a recurrent and commonly disabling primary headache disorder that
      affects over 17% of women and 5%-8% of men. Migraine susceptibility is
      multifactorial with genetic, hormonal and environmental factors all playing an
      important role. The physiopathology of migraine is complex and still not fully
      understood. Many different neuropeptides, neurotransmitters and brain pathways
      have been implicated. In connection with the myriad mechanisms and pathways
      implicated in migraine, a variety of multisystemic comorbidities (e.g.,
      cardiovascular, psychiatric and other neurological conditions) have been found to
      be closely associated with migraine. Recent reports demonstrate an increased
      frequency of gastrointestinal (GI) disorders in patients with migraine compared
      with the general population. Helicobacter pylori infection, irritable bowel
      syndrome, gastroparesis, hepatobiliary disorders, celiac disease and alterations
      in the microbiota have been linked to the occurrence of migraine. Several
      mechanisms involving the gut-brain axis, such as a chronic inflammatory response
      with inflammatory and vasoactive mediators passing to the circulatory system,
      intestinal microbiota modulation of the enteric immunological milieu and
      dysfunction of the autonomic and enteric nervous system, have been postulated to
      explain these associations. However, the precise mechanisms and pathways related
      to the gut-brain axis in migraine need to be fully elucidated. In this review, we
      survey the available literature linking migraine with GI disorders. We discuss
      the possible physiopathological mechanisms, and clinical implications as well as
      several future areas of interest for research. 

PMID- 27688655
TI  - Regulation of the serotonin transporter in the pathogenesis of irritable bowel
      syndrome.
AB  - Serotonin (5-HT) and the serotonin transporter (SERT) have earned a tremendous
      amount of attention regarding the pathogenesis of irritable bowel syndrome (IBS).
      Considering that enteric 5-HT is responsible for the secretion, motility and
      perception of the bowel, the involvement of altered enteric 5-HT metabolism in
      the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly
      associated with depressed SERT mRNA in patients with IBS compared with healthy
      controls. The expression difference of SERT between IBS patients and healthy
      controls might suggest that SERT plays an essential role in IBS pathogenesis, and
      SERT was expected to be a novel therapeutic target for IBS. Progress in this area
      has begun to illuminate the complex regulatory mechanisms of SERT in the etiology
      of IBS. In this article, current insights regarding the regulation of SERT in IBS
      are provided, including aspects of SERT gene polymorphisms, microRNAs, immunity
      and inflammation, gut microbiota, growth factors, among others. Potential SERT
      directed therapies for IBS are also described. The potential regulators of SERT
      are of clinical importance and are important for better understanding IBS
      pathophysiology and therapeutic strategies. 

PMID- 27688658
TI  - Carbonic anhydrase enzymes II, VII, IX and XII in colorectal carcinomas.
AB  - AIM: To investigate expression of four alpha-carbonic anhydrases (CAs) in
      colorectal carcinomas (CRC) and compare the results with patients' survival.
      METHODS: Colorectal carcinoma samples from 539 CRC patients and control tissues
      were arranged as tissue microarrays and analyzed with antibodies against CA II,
      CA VII, CA IX, and CA XII. Intensity and extent of staining were both scored from
      0 to 3 in each sample. These enzyme expression levels were then correlated to
      patients' survival and clinicopathological parameters, which were tumor
      differentiation grade and stage, site of tumor, patients' age, and gender. Kaplan
      Meier analysis and Cox regression hazard ratio model were used to analyze
      survival data. RESULTS: CA II and CA XII staining intensities correlated with
      patients' survival in that higher expression indicated poorer prognosis. In Cox
      regression analysis one unit increase in the CA II intensity increased the hazard
      ratio to 1.19 fold (CI: 1.04-1.37, P = 0.009). A significant correlation was also
      found when comparing CA XII staining intensity with survival of CRC patients (HR
      = 1.18, 95%CI: 1.01-1.38, P = 0.036). The extent of CA XII immunostaining did not
      correlate to the patients' survival (P = 0.242, Kaplan-Meier analysis). A
      significant interaction between age group and extent of the CA II staining was
      found. Increased extent of CA II had a significant hazard ratio among patients 65
      years and older (1.42, 95%CI: 1.16-1.73, P = 0.0006). No correlations were found
      between CA VII (intensity P = 0.566, extent P = 0.495, Kaplan-Meier analysis), or
      CA IX (intensity P = 0.879, extent P = 0.315, Kaplan-Meier analysis)
      immunostaining results and survival, or the other parameters. CONCLUSION: The
      present findings indicate that CA II and CA XII could be useful in predicting
      survival in CRC.

PMID- 27688660
TI  - Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014.
AB  - AIM: To assess the etiology of chronic liver diseases (CLD) from 1998 to 2014 at
      the outpatient clinic of Gastroenterology of the main hospital in Northwest of
      Italy among those dedicated to hepatology. METHODS: A random sample of charts of
      patients referred to for increased liver enzymes between January 1998 and
      December 2006, and between January 2012 and December 2014 were reviewed. Etiology
      search included testing for hepatitis B virus (HBV), hepatitis C virus (HCV),
      autoimmune hepatitis, primary biliary cirrhosis, Wilson's disease and hereditary
      hemocromatosis. A risky alcohol consumption was also considered. Non-alcoholic
      fatty liver disease (NAFLD) was diagnosed in patients with histological and/or
      ultrasound evidence of steatosis/steatohepatitis, and without other causes of
      CLD. RESULTS: The number of patients included was 1163. Of them, 528 (45%) had
      positivity for HCV and 85 (7%) for HBV. Among the virus-free patients, 417 (36%)
      had metabolic disorders whereas the remaining had history of alcohol abuse, less
      prevalent causes of CLD or concomitant conditions. In comparison to 1998-2000
      (41%), a reduction of HCV alone-related cases was detected during the periods
      2001-2003 (35%, OR = 0.75, 95%CI: 0.53-1.06), 2004-2006 (33%, OR = 0.70, 95%CI:
      0.50-0.97) and 2012-2014 (31%, OR = 0.64, 95%CI: 0.46-0.91). On the contrary, in
      comparison to 1998-2000 (31%), metabolic-alone disorders increased in the period
      2004-2006 (39%, OR = 1.37, 95%CI: 0.99-1.91) and 2012-2014 (41%, OR = 1.53,
      95%CI: 1.09-2.16). The other etiologies remained stable. The increase of
      incidence of metabolic-alone etiology during the period 2004-2006 and 2012-2014
      tended to be higher in older patients (>= 50 years) compared to younger (P =
      0.058). CONCLUSION: In the Northwest of Italy, during this study period, the
      prevalence of HCV infection decreased notably whereas that of NAFLD increased.

PMID- 27688659
TI  - Hepatocyte isolation from resected benign tissues: Results of a 5-year
      experience.
AB  - AIM: To analyze retrospectively a 5-year experience of human hepatocyte isolation
      from resected liver tissues with benign disease. METHODS: We established a method
      of modified four-step retrograde perfusion to isolate primary human hepatocytes.
      Samples were collected from the resected livers of patients with intrahepatic
      duct calculi (n = 7) and liver hemangioma (n = 17). Only the samples weighing >=
      15 g were considered suitable for hepatocyte isolation. By using the standard
      trypan blue exclusion technique, hepatocyte viability and yield were immediately
      determined after isolation. RESULTS: Twenty-four liver specimens, weighing 15-42
      g, were immediately taken from the margin of the removed samples and transferred
      to the laboratory for hepatocyte isolation. Warm ischemia time was 5-35 min and
      cold ischemia time was 15-45 min. For the 7 samples of intrahepatic duct calculi,
      the method resulted in a hepatocyte yield of 3.49 +/- 2.31 * 10(6) hepatocytes/g
      liver, with 76.4% +/- 10.7% viability. The 17 samples of liver hemangioma had
      significantly higher yield of cells (5.4 +/- 1.71 * 10(6) cells/g vs 3.49 +/-
      2.31 * 10(6) cells/g, P < 0.05) than the samples of intrahepatic duct calculi.
      However, there seems to be no clear difference in cell viability (80.3% +/- 9.67%
      vs 76.4% +/- 10.7%, P > 0.05). We obtained a cell yield of 5.31 +/- 1.87 * 10(6)
      hepatocytes/g liver when the samples weighed > 20 g. However, for the tissues
      weighing <= 20 g, a reduction in yield was found (3.08 +/- 1.86 * 10(6) cells/g
      vs 5.31 +/- 1.87 * 10(6) cells/g, P < 0.05). CONCLUSION: Benign diseased livers
      are valuable sources for large-number hepatocyte isolation. Our study represents
      the largest number of primary human hepatocytes isolated from resected specimens
      from patients with benign liver disease. We evaluated the effect of donor liver
      characteristics on cell isolation, and we found that samples of liver hemangioma
      can provide better results than intrahepatic duct calculi, in terms of cell
      yield. Furthermore, the size of the tissues can affect the outcome of hepatocyte
      isolation.

PMID- 27688661
TI  - Development of a prognostic scoring system for resectable hepatocellular
      carcinoma.
AB  - AIM: To develop a prognostic scoring system for overall survival (OS) of patients
      undergoing liver resection (LR) for hepatocellular carcinoma (HCC). METHODS:
      Consecutive patients who underwent curative LR for HCC between 2000 and 2013 were
      identified. The series was randomly divided into a training and a validation set.
      A multivariable Cox model for OS was fitted to the training set. The beta
      coefficients derived from the Cox model were used to define a prognostic scoring
      system for OS. The survival stratification was then tested, and the prognostic
      scoring system was compared with the European Association for the Study of the
      Liver (EASL)/American Association for the Study of Liver Diseases (AASLD)
      surgical criteria by means of Harrell's C statistics. RESULTS: A total of 917
      patients were considered. Five variables independently correlated with post-LR
      survival: Model for End-stage Liver Disease score, hepatitis C virus infection,
      number of nodules, largest diameter and vascular invasion. Three risk classes
      were identified, and OS for the three risk classes was significantly different
      both in the training (P < 0.0001) and the validation set (P = 0.0002). Overall,
      69.4% of patients were in the low-risk class, whereas only 37.8% were eligible to
      surgery according to EASL/AASLD. Survival of patients in the low-risk class was
      not significantly different compared with surgical indication for EASL/AASLD
      guidelines (77.2 mo vs 82.5 mo respectively, P = 0.22). Comparison of Harrell's C
      statistics revealed no significant difference in predictive power between the two
      systems (-0.00999, P = 0.667). CONCLUSION: This study established a new
      prognostic scoring system that may stratify HCC patients suitable for surgery,
      expanding surgical eligibility with respect to EASL/AASLD criteria with no harm
      on survival.

PMID- 27688662
TI  - Clinicopathological features of alpha-fetoprotein producing early gastric cancer
      with enteroblastic differentiation.
AB  - AIM: To investigate clinicopathological features of early stage gastric cancer
      with enteroblastic differentiation (GCED). METHODS: We retrospectively
      investigated data on 6 cases of early stage GCED and 186 cases of early stage
      conventional gastric cancer (CGC: well or moderately differentiated
      adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic
      mucosal resection from September 2011 to February 2015 in our hospital. GCED was
      defined as a tumor having a primitive intestine-like structure composed of
      cuboidal or columnar cells with clear cytoplasm and immunohistochemical
      positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were
      compared between GCED and CGC: age, gender, location and size of tumor,
      macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion,
      positive horizontal and vertical margin, curative resection rate. RESULTS: Six
      cases (5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer
      with a GCED component and 186 cases (139 males, 47 females; mean age 72.7 years;
      209 lesions) of early stage CGC were investigated. Mean tumor diameters were
      similar but rates of submucosal invasion, lymphatic invasion, venous invasion,
      and non-curative resection were higher in GCED than CGC (66.6% vs 11.4%, 33.3% vs
      2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal
      invasion was not revealed endoscopically or by preoperative biopsy.
      Histologically, in GCED the superficial mucosal layer was covered with a CGC
      component. The GCED component tended to exist in the deeper part of the mucosa to
      the submucosa by lymphatic and/or venous invasion, without severe stromal
      reaction. In addition, Glypican 3 was the most sensitive marker for GCED
      (positivity, 83.3%), immunohistochemically. CONCLUSION: Even in the early stage
      GCED has high malignant potential, and preoperative diagnosis is considered
      difficult. Endoscopists and pathologists should know the clinicopathological
      features of this highly malignant type of cancer.

PMID- 27688664
TI  - Pregnancy and inflammatory bowel disease: Do we provide enough patient education?
      A British study of 1324 women.
AB  - AIM: To examine patient knowledge and factors influencing knowledge about
      pregnancy in British women with inflammatory bowel disease (IBD). METHODS: This
      is a post hoc analysis of a study of female members of Crohn's and Colitis United
      Kingdom, aged 18-45 years who were sent an online questionnaire recording patient
      demographics, education, employment, marital status, and disease characteristics.
      Disease related pregnancy knowledge was recorded using Crohn's and colitis
      pregnancy knowledge score (CCPKnow). RESULTS: Of 1324 responders, 776 (59%)
      suffered from Crohn's disease, 496 (38%) from ulcerative colitis and 52 (4%) from
      IBD-uncategorised. CCPKnow scores were poor (0-7) in 50.8%, adequate (8-10) in
      23.6%, good (11-13) in 17.7% and very good (>= 14) in 7.8%. Multiple linear
      regression analysis revealed that higher CCPKnow scores were independently
      associated with higher educational achievement (P < 0.001), younger age at
      diagnosis (P = 0.003) and having consulted a health care professional about
      pregnancy and IBD (P = 0.001). CONCLUSION: Knowledge was poor in 50%. Speaking
      with health-care professionals was a modifiable factor associated with better
      knowledge. This illustrates the importance of disease related pregnancy
      education.

PMID- 27688663
TI  - FOCUS: Future of fecal calprotectin utility study in inflammatory bowel disease.
AB  - AIM: To evaluate the perspective of gastroenterologists regarding the impact of
      fecal calprotectin (FC) on the management of patients with inflammatory bowel
      disease (IBD). METHODS: Patients with known IBD or symptoms suggestive of IBD for
      whom the physician identified that FC would be clinically useful were recruited.
      Physicians completed an online "pre survey" outlining their rationale for the
      test. After receipt of the test results, the physicians completed an online "post
      survey" to portray their perceived impact of the test result on patient
      management. Clinical outcomes for a subset of patients with follow-up data
      available beyond the completion of the "post survey" were collected and analyzed.
      RESULTS: Of 373 test kits distributed, 290 were returned, resulting in 279 fully
      completed surveys. One hundred and ninety patients were known to have IBD; 147
      (77%) with Crohn's Disease, 43 (21%) Ulcerative Colitis and 5 (2%) IBD
      unclassified. Indications for FC testing included: 90 (32.2%) to differentiate a
      new diagnosis of IBD from Irritable Bowel Syndrome (IBS), 85 (30.5%) to
      distinguish symptoms of IBS from IBD in those known to have IBD and 104 (37.2%)
      as an objective measure of inflammation. FC levels resulted in a change in
      management 51.3% (143/279) of the time which included a significant reduction in
      the number of colonoscopies (118) performed (P < 0.001). Overall, 97.5% (272/279)
      of the time, the physicians found the test sufficiently useful that they would
      order it again in similar situations. Follow-up data was available for 172
      patients with further support for the clinical utility of FC provided.
      CONCLUSION: The FC test effected a change in management 51.3% of the time and
      receipt of the result was associated with a reduction in the number of
      colonoscopies performed.

PMID- 27688665
TI  - Clinical guidelines of non-alcoholic fatty liver disease: A systematic review.
AB  - AIM: To perform a systematic review to grade guidelines and present
      recommendations for clinical management of non-alcoholic fatty liver disease
      (NAFLD). METHODS: A database search was conducted on PubMed for guidelines
      published before May 2016, supplemented by reviewing relevant websites. The
      Appraisal of Guidelines for Research and Evaluation (ARGEE) Instrument II was a
      tool designed to appraise the methodological rigor and transparency in which a
      clinical guideline is developed and it is used internationally. It was used to
      appraise the quality of guidelines in this study. The inclusion criteria include:
      clinical NAFLD guidelines for adults, published in English, and released by
      governmental agencies or key organizations. RESULTS: Eleven guidelines were
      included in this study. Since 2007, guidelines have been released in Asia (3 in
      China, 1 in South Korea, and 1 in Japan), Europe (1 in Italy), America (1 in
      United States and 1 in Chile) and three international agencies [European
      associations joint, Asia-Pacific Working Party and World Gastroenterology
      Organization (WGO)]. Using the ARGEE II instrument, we found US 2012 and Europe
      2016 had the highest scores, especially in the areas of rigor of development and
      applicability. Additionally, Italy 2010 and Korea 2013 also presented
      comprehensive content, rigorous procedures and good applicability. And WGO 2014
      offered various algorithms for clinical practice. Lastly, a practical algorithm
      for the clinical management was developed, based on the recommended guidelines.
      CONCLUSION: This is the first systematic review of NAFLD guidelines. It may yield
      insights for physicians and policy-makers in the development and application of
      guidelines.

PMID- 27688666
TI  - Diagnosis of colonic amebiasis and coexisting signet-ring cell carcinoma in
      intestinal biopsy.
AB  - Amebiasis is uncommon in developed countries. Several case reports in the
      literature emphasize that both the presenting symptoms and the radiological
      findings of colonic amebiasis closely resemble more common conditions, such as
      idiopathic inflammatory bowel disease and gastro-intestinal malignancy. We
      describe a unique case of colonic amebiasis (amebomas) coexisting with signet
      ring cell carcinoma of the ileocecal valve, the cecum and the appendix.
      Endoscopically, the ulcerated tumor was indistinguishable from the ulcerations
      and pseudotumors (amebomas) detected in the ascending colon. Histological
      examination of biopsy specimens revealed the pathognomonic features of protozoa
      with ingested erythrocytes in combination with signet-ring cell infiltration. The
      author concludes that amebiasis may not only mimic carcinoma but, rarely, may
      coexist with carcinoma in the same patient. Clinicians and pathologists should be
      aware of this possibility in order not to delay diagnosis and treatment of
      malignant disease. 

PMID- 27688668
TI  - Editorial comments on "Mitral Valve Replacement for Mitral Stenosis: 15 years
      Single Center Experience".

PMID- 27688667
TI  - Case of a tumor comprising gastric cancer and duodenal neuroendocrine tumor.
AB  - The present report describes a rare case of a tumor composed of early gastric
      cancer and a duodenal neuroendocrine tumor (NET). A 78-year-old woman underwent
      esophagogastroduodenoscopy at a local institution for screening of the upper
      gastrointestinal tract which revealed a protruded tumor through the pyloric ring
      from the pyloric antrum. The tumor was too large to treat at the facility;
      consequently, she was referred to our hospital for further management.
      Esophagogastroduodenoscopy with tumor biopsy of the lesion revealed the diagnosis
      of early gastric cancer. Endoscopic submucosal dissection was performed with
      sufficient free margins in both vertical and horizontal directions.
      Histopathological findings showed NET confined to the submucosal layer and
      covered by well-differentiated adenocarcinoma. Immunohistochemical stainings
      showed that the two lesions existed continuously. While the possibility of a
      collision cancer was considered, it was suggested that the two lesions existed
      continuously. Finally, the tumor was diagnosed as gastric cancer composed of
      duodenal NET G1, with a lymphatic invasion of NET component. 

PMID- 27688669
TI  - Recombinant activated factor VII for uncontrolled bleeding postcardiac surgery.
AB  - A retrospective observational study to review the safety and efficacy of rFVIIa
      in persistent hemorrhage in post cardiac surgical patients. METHODS: Patients who
      had bleeding of 3 ml/kg/h or more for 2 consecutive hours after cardiac surgery
      were arranged into two groups; control group, who received conventional treatment
      and rFVIIa group, who received conventional treatment and rFVIIa. RESULTS: There
      was no significant difference in demographic and surgical characteristics of both
      groups. The chest tube output significantly decreased in the rFVIIa group
      compared to the other group 4 hours after admission {1.4 (IQR: 1-2.2) ml/kg/h vs
      3.9 (IQR: 3.1-5.6) ml/kg/h; p = 0.004} and continues to be significant till 9
      hours after CSICU admission {0.6 (IQR: 0.4-1.1) ml/kg/h vs 1.9 (IQR: 1.2-2.2)
      ml/kg/h; p = 0.04}. The median number of blood products units transfused to
      rFVIIa group was significantly lower compared to control group in the period from
      3-12 hours after CSICU admission. 13 (5.5%) patients in rFVIIa group had
      Thromboembolic adverse events (TAE) compared to 7 (2.4%) patients in other group
      p = 0.27. 8 patients in the rFVIIa group needed reexploration compared to 19
      patients in the other group, p = 0.01. No significant difference was noticed
      between the 2 groups regarding: new onset renal failure, median number of
      mechanical ventilator days, pneumonia, mediastinitis, ICU and hospital lengths of
      stay, survival at 30 days and at discharge. CONCLUSION: In this analysis, rFVIIa
      succefully reduced the chest tube bleeding and blood products transfused during
      severe post cardiac surgical bleeding. However, safety of rFVIIa remains unclear.
      Prospective controlled trials are still needed to confirm the role of rFVIIa.

PMID- 27688670
TI  - Mitral valve replacement for mitral stenosis: A 15-year single center experience.
AB  - OBJECTIVES: Mitral valve replacement with either a bioprosthetic or a mechanical
      valve is the treatment of choice for severe mitral stenosis. However, choosing a
      valve implant type is still a subject of debate. This study aimed to evaluate and
      compare the early and late outcomes of mitral valve replacement [mechanical (MMV)
      vs. bioprosthetic (BMV)] for severe mitral stenosis. METHODS: A retrospective
      cohort study was performed on data involving mitral stenosis patients who have
      undergone mitral valve replacement with either BMV (n = 50) or MMV (n = 145)
      valves from 1999 to 2012. Data were collected from the patients' records and
      follow-up through telephone calls. Data were analyzed for early and late
      mortality, New York Heart Association (NYHA) functional classes, stroke, pre- and
      postoperative echocardiographic findings, early and late valve-related
      complications, and survival. Chi-square test, logistic regression, Kaplan-Meier
      curve, and dependent proportions tests were some of the tests employed in the
      analysis. RESULTS: A total of 195 patients were included in the study with a 30
      day follow-up echocardiogram available for 190 patients (97.5%), while 103 (53%)
      were available for follow-up over the telephone. One patient died early
      postoperatively; twelve patients died late in the postoperative period, six in
      the bioprosthesis group and six in the mechanical group. The late mortality had a
      significant association with postoperative stroke (p < 0.001) and postoperative
      NYHA Classes III and IV (p = 0.002). Postoperative NYHA class was significantly
      associated with age (p = 0.003), pulmonary disease (p = 0.02), mitral valve
      implant type (p = 0.01), and postoperative stroke (p = 0.02); 14 patients had
      strokes in the mechanical (9) and in the bioprosthetic (5) groups. NYHA classes
      were significantly better after the replacement surgeries (p < 0.001). BMV were
      significantly associated with worse survival (p = 0.03), worse NYHA
      postoperatively (p = 0.01), and more reoperations (p = 0.006). Survival was
      significantly better with MMV (p = 0.03). When the two groups were matched for
      age and mitral regurgitation, the analysis revealed that BMV were significantly
      associated with reoperations (p = 0.02) but not significantly associated with
      worse survival (p = 0.4) or worse NYHA (p = 0.4). CONCLUSION: MMV replacement in
      mitral stenosis patients is associated with a lower reoperation rate, but there
      was no difference in survival compared with BMV replacement.

PMID- 27688671
TI  - Quality of anticoagulation control among patients with atrial fibrillation: An
      experience of a tertiary care center in Saudi Arabia.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common chronic rhythm disorder.
      Patients with AF are at an increased risk of ischemic stroke. Therefore, optimal
      anticoagulation is essential to reduce the risk of stroke. The aim of this study
      was to assess the level of anticoagulation control achieved in patients with
      nonvalvular AF receiving medical care in a tertiary care hospital. METHODS: This
      was a retrospective cohort study in ambulatory care clinics at tertiary care
      hospital in Saudi Arabia. We included 110 nonvalvular AF patients treated with
      warfarin for at least 3 months at King Abdulaziz Medical City, Riyadh, Saudi
      Arabia, between May 1, 2012, and July 31, 2012. Thereafter, international
      normalized ratio results were collected for 1 year. Anticoagulation control was
      assessed by calculating time within therapeutic range (TTR) as per the Rosendaal
      method. RESULTS: The mean age was 64.9 +/- 16.5 years; 60.9% were female. The
      mean TTR was 59%. Almost one third of the patients (32.7%) had poor
      anticoagulation control; TTR of <50%. Poor anticoagulation control was
      significantly associated with higher CHADS2 (congestive heart failure,
      hypertension, age, diabetes, stroke) score (p = 0.043). TTR was not significantly
      different between men and women. Similarly, TTR was not associated with age or
      duration of anticoagulation. There was no adequate information to assess the
      effect of other factors such as diet, compliance, and level of education on
      anticoagulation. Thirty-one patients (28.2%) had a history of prior stroke. The
      overall quality of anticoagulation was not significantly different between
      patients with and without stroke, (TTR was 56.3% and 60.1%, respectively; p =
      0.46). CONCLUSION: Quality of anticoagulation in patients with AF receiving
      medical care in a tertiary care hospital was suboptimal, with nearly 40% of the
      time spent outside the therapeutic range. Methods to improve anticoagulation
      control among patients with AF should be implemented.

PMID- 27688672
TI  - Predictors of cardio pulmonary resuscitation outcome in postoperative cardiac
      children.
AB  - BACKGROUND: Outcomes of cardiopulmonary resuscitation (CPR) in children with
      congenital heart disease have improved and many children have survived after an
      in-hospital cardiac arrest. AIM: The purpose of this study is to determine
      predictors of poor outcome after CPR in critical children undergoing cardiac
      surgery. METHODS: We conducted a retrospective chart review and data analysis of
      all CPR records and charts of all postoperative cardiac children who had a
      cardiac arrest and required resuscitation from 2011 until 2015. Demographic, pre
      operative, and postoperative data were reviewed and analyzed. RESULTS: During the
      study period, 18 postoperative pediatric cardiac patients had CPR. Nine of them
      had return of spontaneous circulation and survived (50%). On average CPR was
      required on the 3(rd) postoperative day. Univariate analysis demonstrated that
      poor outcome was associated with higher lactic acid measured 4-6 hours prior to
      arrest (p = 0.045; p = 0.02) coupled with higher heart rate (p = 0.031), lower O2
      saturation (p = 0.01), and lower core body temperature (p = 0.019) recorded 6
      hours before arrest. Nonsurvival required longer resuscitation duration and more
      epinephrine doses (p < 0.05). CONCLUSION: Higher heart rate, lower core body
      temperature, lower O2 saturation, and higher lactic acid measured 6 hours before
      arrest are possible predictors of poorer outcome and mortality following CPR in
      postoperative cardiac children.

PMID- 27688673
TI  - Arterial stiffness in metabolic syndrome.
AB  - Arterial stiffness is increasingly recognized as an important determinant of
      cardiovascular risk and may be directly involved in the process of
      atherosclerosis. As atherosclerosis leads to increased arterial resistance and
      decrease the flow propagation speed within the arterial lumen, a similar decrease
      in aortic flow propagation with increased downstream resistance is detected, so
      aortic flow propagation velocity AVP was evaluated in many studies as a new
      parameter of aortic stiffness. AIM: To measure arterial stiffness using the new
      parameter AVP and compare it to flow mediated dilatation FMD as a parameter of
      endothelial dysfunction in patients with metabolic syndrome MS. METHODS: AVP
      (assessed by transthoracic echocardiography) and FMD (assessed by brachial artery
      reactivity test) were measured in 100 patients with MS (Group 1) and were
      compared to 14 normal subjects (Group 2). RESULTS: Patients with MS had
      significantly lower values of AVP as compared to the normal subjects; 36 +/- 5
      cm/s vs 57 +/- 5, p < 0.05, and lower FMD; 6% +/- 1 vs 17 +/- 3 p < 0.05 as well,
      there was significant correlations between AVP and FMD (r = 0.89, p < 0.001).
      CONCLUSION: Transthoracic echocardiographic determination of AVP is a simple
      practical method and correlates well with FMD in patients with MS.

PMID- 27688674
TI  - Single coronary artery from right aortic sinus in a very elderly patient.
AB  - In the absence of other associated cardiac anomalies, single coronary artery
      (SCA) per se is a rare anomaly detected during coronary angiography or autopsy.
      Various types of SCA detected during coronary angiography have already been
      described. We herein report a type of SCA originating from the right sinus of
      Valsalva, with the right circumflex, left circumflex, and left anterior
      descending coronary arteries arising from the proximal part of the SCA in a 76
      year-old female patient. She developed ventricular fibrillation during coronary
      angiography, which calls for caution while performing a coronary angiogram in
      such patients. 

PMID- 27688675
TI  - A continuous murmur following a nonpenetrating chest trauma.
AB  - We reported a rare case of non-penetrating chest trauma-induced fistula from the
      right sinus of Valsalva to the right heart chambers. The ruptured sinus of
      Valsalva aneurysm was diagnosed preoperatively and operated on successfully. The
      rarity of this case highlights the need for a precise preoperative diagnosis, the
      role of transthoracic echocardiography, and the importance of a prompt surgical
      management. 

PMID- 27688676
TI  - Ortner's syndrome: Cardiovocal syndrome caused by aortic arch pseudoaneurysm.
AB  - 72-year-old hypertensive presented with two weeks history of left sided chest
      pain and hoarseness. Workup demonstrated a pseudoaneurysm in the lesser curvature
      of the distal aortic arch opposite the origin of the left subclavian artery from
      a penetrating atherosclerotic ulcer. Following a left carotid-subclavian bypass,
      endovascular stenting of the aorta was performed excluding the pseudoaneurysm.
      Patient had excellent angiographic results post-stenting. Follow up at 12 weeks
      demonstrated complete resolution of his symptoms and good stent position with no
      endo-leak. Ortner's syndrome describes vocal changes caused by cardiovascular
      pathology. It should be included in the differential diagnosis of patients with
      cardiovascular risk factors presenting with hoarseness. This case demonstrates
      the use of endovascular stents to treat the causative pathology with resolution
      of symptoms. In expert hands, it represents low risk, minimally invasive
      therapeutic strategy with excellent early results in patients who are high risk
      for open procedure. 

PMID- 27688677
TI  - Aorto-left atrial fistula: Rare cause of acute cardiac failure in a previously
      healthy individual.
AB  - Complications of valvular infective endocarditis involving the peri-annular
      region puts the patient at a significantly high risk of adverse outcomes
      including heart failure and death. The "mitral-aortic intervalvular fibrosa" is
      relatively avascular and offers little resistance to the spread of abscesses,
      aneurysm, and fistula formation. Aorto-cavitary fistulous tract formation in the
      setting of native valve infective endocarditis is associated with higher rates of
      heart failure, ventricular septal defect, and atrioventricular block than
      nonruptured abscesses. Thus, a high index of suspicion is needed for rapid and
      accurate diagnosis, which can guide further management. A transesophageal
      echocardiogram is the preferred modality of investigation in such cases.
      Staphylococci are reported to be the most common pathogen involved. In addition
      to early antibiotic therapy, prompt surgical intervention might save lives in
      these scenarios. 

PMID- 27688679
TI  - Pheochromocytoma presenting as an acute coronary syndrome complicated by acute
      heart failure: The challenge of a great mimic.
AB  - Pheochromocytoma is a rare neuroendocrine tumor with a highly variable clinical
      presentation. The serious and potentially lethal cardiovascular complications of
      these tumors are related to the effects of secreted catecholamines. We describe a
      case of a 50-year-old woman urgently admitted to our hospital because of symptoms
      and clinical and instrumental findings consistent with an acute coronary syndrome
      complicated by acute heart failure. Urgent coronary angiography showed normal
      coronary arteries. During her hospital stay, the recurrence of episodes
      characterized by a sudden increase in blood pressure, cold sweating, and nausea
      allowed us to hypothesize a pheochromocytoma. The diagnosis was confirmed by
      elevated levels of urinary catecholamines and by the finding of a left adrenal
      mass on magnetic resonance imaging. The patient underwent left adrenalectomy.
      Therefore, the initial diagnosis was critically reappraised and reviewed as a
      cardiac manifestation of a pheochromocytoma during catecholaminergic crisis. 

PMID- 27688678
TI  - All that looks like "Brugada" is not "Brugada": Case series of Brugada phenocopy
      caused by hyponatremia.
AB  - Brugada syndrome (BS), a life-threatening channelopathy associated with reduced
      inward sodium current due to dysfunctional sodium channels, is characterized by
      ST-segment elevation with downsloping "coved type" (type 1) or "saddle back"
      (type 2) pattern in V1-V3 precordial chest leads (1, 2). Brugada phenocopy, a
      term describing conditions inducing Brugada-like pattern of electrocardiogram
      (EKG) manifestations in patients without true BS, is an emerging condition (3).
      We describe a case series of Brugada phenocopy with hyponatremia. 

PMID- 27688680
TI  - Cardiac resynchronization therapy and challenging coronary sinus angiography.

PMID- 27688682
TI  - Gambling Modes and State Gambling Laws: Changes from 1999 to 2011 and Beyond.

PMID- 27688681
TI  - Ethical Considerations in Exposure Therapy With Children.
AB  - Despite the abundance of research that supports the efficacy of exposure therapy
      for childhood anxiety disorders and OCD, negative views and myths about the
      harmfulness of this treatment are prevalent. These beliefs contribute to the
      underutilization of this treatment and less robust effectiveness in community
      settings compared to randomized clinical trials. Although research confirms that
      exposure therapy is efficacious, safe, tolerable, and bears minimal risk when
      implemented correctly, there are unique ethical considerations in exposure
      therapy, especially with children. Developing ethical parameters around exposure
      therapy for youth is an important and highly relevant area that may assist with
      the effective generalization of these principles. The current paper reviews
      ethical issues and considerations relevant to exposure therapy for children and
      provides suggestions for the ethical use of this treatment.

PMID- 27688684
TI  - Alleviated negative rather than positive attentional bias in patients with
      depression in remission: an eye-tracking study.
AB  - Objective To investigate attentional bias toward happy and sad faces in remitted
      depressed (RD) patients compared with healthy control (HC) subjects. Methods This
      cross-sectional study enrolled RD patients and sex- and age-matched HC subjects.
      Eye movement data were acquired for all study participants while free viewing a 2
      * 2 matrix of emotional faces. The attentional bias toward different emotional
      faces and whether the attention maintenance components generated attentional bias
      in the RD patients were analysed by comparing the attentional modes of the RD
      group with the HC group. Results A total of 27 RD patients and 27 HC subjects
      were analysed in this study. The RD and HC groups exhibited no significant
      differences toward first fixation location and initial attentional maintenance.
      In later attentional maintenance, the RD group showed significantly less
      attentional bias toward happy faces, but there were no significant differences in
      their attentional bias toward sad faces, compared with the HC group. Conclusions
      This present study showed that the negative attentional bias of RD patients was
      successfully eased, but their positive attentional bias was still insufficient.

PMID- 27688683
TI  - The effect and mechanism of action of metformin on in vitro FaDu cell
      proliferation.
AB  - Objective To investigate the effect and mechanism of action of metformin on
      proliferation of a human hypopharyngeal carcinoma cell line (FaDu). Methods FaDu
      cells were treated with metformin (25-125 mmol/l). Cell proliferation was
      evaluated via CCK-8 assay. Real-time quantitative reverse transcription
      polymerase chain reaction was used to evaluate microRNA (miR)-21-5p and PDCD4
      (programmed cell death 4) expression. PDCD4 protein was quantified by Western
      blot. Results Metformin significantly inhibited FaDu cell proliferation in a dose
      (25-100 mmol/l) and time-dependent manner (12 h-36 h), significantly
      downregulated miR-21-5p, and upregulated PDCD4 mRNA and protein expression.
      Conclusions Metformin significantly inhibited FaDu cell proliferation , possibly
      via downregulation of miR-21-5p and upregulation of PDCD4.

PMID- 27688685
TI  - Comparison of saddle, lumbar epidural and caudal blocks on anal sphincter tone: A
      prospective, randomized study.
AB  - Objective To compare the effects of saddle, lumbar epidural and caudal blocks on
      anal sphincter tone using anorectal manometry. Methods Patients undergoing
      elective anorectal surgery with regional anaesthesia were divided randomly into
      three groups and received a saddle (SD), lumbar epidural (LE), or caudal (CD)
      block. Anorectal manometry was performed before and 30 min after each regional
      block. The degree of motor blockade of the anal sphincter was compared using the
      maximal resting pressure (MRP) and the maximal squeezing pressure (MSP). Results
      The study analysis population consisted of 49 patients (SD group, n = 18; LE
      group, n = 16; CD group, n = 15). No significant differences were observed in the
      percentage inhibition of the MRP among the three regional anaesthetic groups.
      However, percentage inhibition of the MSP was significantly greater in the SD
      group (83.6 +/- 13.7%) compared with the LE group (58.4 +/- 19.8%) and the CD
      group (47.8 +/- 16.9%). In all groups, MSP was reduced significantly more than
      MRP after each regional block. Conclusions Saddle block was more effective than
      lumbar epidural or caudal block for depressing anal sphincter tone. No
      differences were detected between lumbar epidural and caudal blocks.

PMID- 27688686
TI  - Laparoendoscopic single-site surgery varicocelectomy versus conventional
      laparoscopic varicocele ligation: A meta-analysis.
AB  - Objective To perform a meta-analysis of data from available published studies
      comparing laparoendoscopic single-site surgery varicocelectomy (LESSV) with
      conventional transperitoneal laparoscopic varicocele ligation. Methods A
      comprehensive data search was performed in PubMed and Embase to identify
      randomized controlled trials and comparative studies that compared the two
      surgical approaches for the treatment of varicoceles. Results Six studies were
      included in the meta-analysis. LESSV required a significantly longer operative
      time than conventional laparoscopic varicocelectomy but was associated with
      significantly less postoperative pain at 6 h and 24 h, a shorter recovery time
      and greater patient satisfaction with the cosmetic outcome. There was no
      difference between the two surgical approaches in terms of postoperative semen
      quality or the incidence of complications. Conclusion These data suggest that
      LESSV offers a well tolerated and efficient alternative to conventional
      laparoscopic varicocelectomy, with less pain, a shorter recovery time and better
      cosmetic satisfaction. Further well-designed studies are required to confirm
      these findings and update the results of this meta-analysis.

PMID- 27688687
TI  - Incidence and characteristics of hepatitis E virus infection in children in
      Assiut, Upper Egypt.
AB  - Objective To describe the characteristics of hepatitis E virus (HEV) infection in
      a cohort of children from Upper Egypt using data from a large multicentre
      prospective study of acute viral hepatitis (AVH). Methods Data from subjects aged
      2-18 years with AVH or close contacts of those with AVH found to have
      asymptomatic AVH were included in the analysis. Information concerning medical
      history, clinical examination, liver function tests and screening for
      hepatotropic viruses was recorded and analysed. Results A total of 123 patients
      (73 boys, 50 girls) were included in the analysis. Of these, 33 (26.8%) had HEV
      infection, 17 (13.8%) had hepatitis A virus infection, 10 (8.1%) had hepatitis B
      virus infection, 14 (11.4%) had cytomegalovirus hepatitis, five (4.1%) had
      autoimmune hepatitis, 11 (8.9%) had hepatitis due to mixed viral infections and
      33 (26.8%) had non A-E hepatitis. Overall, 38 (30.9%) had infection with HEV. HEV
      infection was significantly higher among those using underground wells as a water
      source compared with tap water. Liver enzymes were significantly raised in
      patients with non-HEV infection compared with those with HEV infection.
      Conclusions HEV is a significant cause of AVH among children in Upper Egypt.
      Contamination of drinking water appears to be a major source of infection.
      Screening for HEV should be considered in all Egyptian children with AVH.

PMID- 27688688
TI  - Incidence of insulin resistance and diabetes in patients with portosystemic
      shunts without liver dysfunction.
AB  - Objective To investigate the incidence of insulin resistance (IR) and diabetes in
      patients with chronic hepatic schistosomiasis japonica (HSJ) and portosystemic
      shunts (PSS). Methods Pre- and post-contrasted computed tomography images
      obtained from patients with HSJ and control subjects were reviewed by two
      radiologists who identified and graded any shunting vessels. Anthropometric
      measurements, hepatic enzymes, lipid profile, blood levels of albumin, glucose,
      insulin and homeostasis model assessment (HOMA-2) index of all participants were
      also assessed. Results Fifty-two patients with HSJ and 30 control subjects were
      involved in the study. The coronary, short gastric and perisplenic veins were the
      most common shunting vessels. There were no significant differences between
      patients and controls in terms of body mass index or liver function. The degree
      of shunting vessels, blood glucose, oral glucose tolerance test120/0, insulin,
      HOMA-2 index, glycosylated haemoglobin, cholesterol, high- and low-density
      lipoprotein, and C-reactive protein were significantly higher in the patients
      with IR. A positive correlation was found between the degree of the shunting
      vessels and the HOMA-2 index. Conclusions Patients with chronic HSJ and PSS
      without liver dysfunction had a high incidence of IR and diabetes. The study
      showed that PSS and IR are related and therefore patients with PSS should be
      screened for IR and vice versa.

PMID- 27688689
TI  - Evaluation of a liquid culture system in the detection of mycobacteria at an
      antituberculosis institution in China; A retrospective study.
AB  - Objective A retrospective study comparing the diagnostic performance of the
      BACTECTM MGITTM 960 system (M960 system; BD Worldwide, Franklin Lakes, NJ, USA)
      with Lowenstein-Jensen (L-J) culture to detect mycobacteria in sputum specimens
      from patients with suspected pulmonary tuberculosis (TB). Methods Sputum samples
      were analysed for the presence of acid-fast bacilli (AFB). Samples were
      inoculated into the M960 system and L-J culture. Positive cultures were examined
      for the presence of AFB. Results The M960 method detected significantly more
      positive samples than L-J culture (818/1676 [48.8%] vs 692/1676 [41.3%]). Using L
      J culture as reference, the sensitivity, specificity, positive predictive and
      negative predictive values of the M960 system were 91.0%, 76.1%, 77.0% and 92.2%,
      respectively. The time-to-detection of mycobacteria was 11.78 +/- 5.16 days for
      M960 and 24.17 +/- 8.73 days for L-J. Conclusions The M960 system had better
      diagnostic capability than L-J culture. Clinical value may be maximized by
      combining results from both methods.

PMID- 27688690
TI  - Long-lasting austerity in the Greek health care system: Could it influence the
      efforts to limit the spread of carbapenem-resistance in Europe?

PMID- 27688691
TI  - Effects of acute cigarette smoking on total blood count and markers of oxidative
      stress in active and passive smokers.
AB  - BACKGROUND: Free radicals, as a product of cigarette smoke, are considered to
      have deleterious effects causing oxidative stress. Acute active smoking seems to
      be followed by transient leukocytosis and delayed increase in neutrophil
      activation. The aim of the present study was to investigate the oxidative status
      of smokers and passive non-smokers, as well as the impact that acute cigarette
      smoking has on hematological parameters. METHODS: Thirty-two healthy volunteers,
      16 active smokers (Group A) aged 20-23 years and 16 age-matched, non-smokers
      (Group B), 18 women and 14 men in total, participated voluntarily in the study.
      All subjects did not have any food, drink, or cigarette smoking for eight hours
      before the study. Each time, two active smokers and two non-smokers were exposed
      simultaneously for half an hour to the smoke of two cigarettes smoked
      consecutively by the smokers. Blood was drawn before and after the exposure to
      cigarette smoke. Whole blood was analyzed immediately for total blood count
      parameters and serum was stored in -70(?)C until serum levels of malondialdehyde
      (MDA) and vitamin E (VitE), and total antioxidant capacity (TAC) were determined.
      RESULTS: No statistical significant difference was observed in the values of
      white blood cells and their subpopulations between the two groups and within the
      same group before and after exposure to cigarette smoke. In the group of smokers,
      granulocyte/lymphocyte ratio increased significantly, MDA levels showed
      significant elevation and protective VitE serum levels decreased significantly,
      whereas TAC was reduced, but not significantly, after the exposure. In the group
      of passive, non-smokers the results of the blood count parameters, MDA and VitE
      were similar to Group A, and there was a significant decrease in TAC, as well.
      Between the two groups, only hematocrit values and MDA levels differed
      significantly before the exposure to smoke, and no other significant difference
      was detected before or after the exposure, between active and passive smokers.
      CONCLUSIONS: Acute exposure to cigarette smoking affects hematological indexes
      and oxidative stress biomarkers negatively, in both active and passive smokers,
      with similar results. The outcome seems to be even worse in passive smokers
      regarding oxidative stress and antioxidant protection markers. Elimination of
      cigarette smoking could prevent the adverse effects for smokers, as well as for
      healthy non-smokers in their vicinity. Hippokratia 2015; 19 (4): 293-297.

PMID- 27688692
TI  - Effect of Ramadan fasting on metabolic markers, dietary intake and abdominal fat
      distribution in pregnancy.
AB  - BACKGROUND: The aim of this study is to evaluate the effect of Ramadan
      intermittent fasting on metabolic markers, dietary intake, anthropometric
      measurements, and abdominal visceral fat thickness (VFT) in pregnancy. METHODS:
      Seventy-eight healthy pregnant subjects who had fasted for at least 15 days
      during the month of Ramadan in 2012 and 2013 and 78 controls were included in
      this study. Metabolic markers, dietary intake, anthropometric measurements, and
      ultrasonographic VFT were calculated for each subject before and after Ramadan
      fasting. RESULTS: When before and after Ramadan values in the fasting group were
      compared, we found that daily protein intake was increased (p <0.001), but fat
      and carbohydrate intake remained unchanged. A significant reduction was observed
      in liquid consumption while the frequency of asymptomatic bacteriuria was
      increased. High-density lipoprotein significantly increased, and glycated
      hemoglobin, insulin, and homeostasis model index significantly decreased (p
      =0.005, p =0.01, p <0.001, and p =0.03, respectively). A significant increase in
      ferritin was found (p =0.02). No change was observed in subcutaneous fat
      thickness, while VFT significantly decreased (p =0.08, p =0.005). However, in the
      control group, only ferritin level increased. CONCLUSION: A combined change in
      the number and timing of meals and the portioning of the entire daily intake into
      only two meals per day may have beneficial metabolic effects and reduction in VFT
      during pregnancy. Hippokratia 2015; 19 (4): 298-303.

PMID- 27688693
TI  - Kidney length in healthy members of Balkan endemic nephropathy families.
AB  - BACKGROUND: Kidney size may differ between healthy members of Balkan endemic
      nephropathy (BEN) and non-BEN families. The present study was designed to
      elucidate this, in comparison with values for BEN patients. METHODS: A total of
      71 BEN patients (34 males, 64.4 +/- 12.0 years), 74 healthy BEN family members
      (39 males, 49.1 +/- 12.2 years), and 59 non-BEN family members (19 males, 49.2 +/
      12.3 years) were involved. We measured the longest craniocaudal length and
      minimal parenchymal thickness on each kidney of all examined subjects using
      ultrasound. RESULTS: No significant difference was found between the kidney
      length of healthy subjects from BEN (11.0 +/- 0.8 cm) and non-BEN families (10.9
      +/- 0.8 cm), but kidneys were significantly longer than in BEN patients (9.9 +/-
      1.3 cm). Minimal parenchymal thickness was similar in all three groups. When
      subjects from each group were divided according to estimated glomerular
      filtration rate (eGFR), kidney length of the healthy groups was significantly
      longer than in BEN patients both in stage 1 (p =0.039) and stage 2 (p =0.044) of
      chronic kidney disease. The parental history of BEN was not associated with
      kidney dimensions, eGFR, or urinary excretion of albumin and alpha1
      microglobulin. CONCLUSION: Kidneys of BEN patients were significantly shorter
      than in healthy members of both BEN and non-BEN families, but no difference was
      found in kidney length and parenchymal thickness between healthy members of BEN
      and non-BEN families. No significant association was found between parental
      history of BEN and kidney size and function either in BEN patients or in healthy
      members from BEN families. Hippokratia 2015; 19 (4): 304-308.

PMID- 27688694
TI  - The prevalence of Factor V Leiden, prothrombin G20210A, MTHFR C677T and MTHFR
      A1298C mutations in healthy Turkish population.
AB  - BACKGROUND: Factor V Leiden (FVL), prothrombin gene (PT G20210A) and
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms are the main
      biomarkers used in the evaluation of tendency to venous thromboembolism. Our
      study aimed to investigate the distribution frequencies of these polymorphisms in
      healthy Turks living in the urban Yozgat region.  MATERIAL AND METHODS: This
      study included 90 blood donor candidates. All the donors were apparently healthy,
      and there was no family relationship between them. Mutations including FVL, PT
      G20210A, and MTHFR (C677T, A1298C) were investigated in all participants.
      Screening of polymorphisms was carried out using the SNaPshot(r) multiplex
      system. RESULTS: There were 42 male and 48 female individuals with age range 17
      78 years and mean age 47.5 +/- 13.6 years. The heterozygous FVL mutation was
      noted in 17 (10 male and seven female) donors (19%). FVL mutation was more
      frequently encountered in males than in females (23.8% vs. 12.5%). The
      heterozygous PT G20210A mutation was observed in five (5.5%) of the 90 (three
      male, two female) donors. The prevalence of homozygous polymorphisms of MTHFR
      C677T was 8.8% and of MTHFR A1298C 13.3%. On the other hand, four of the 90
      participants (4.4%) carried none of these polymorphisms. CONCLUSION: This study
      showed that the prevalence of FVL, PT G20210A, MTHFR C677T and MTHFR A1298C
      polymorphisms is quite high, and the coexistence of FVL with other genotypes is
      not rare in a healthy Turkish population living in the Yozgat region. Of course,
      further detailed studies should be performed to support these findings.
      Hippokratia 2015; 19 (4): 309-313.

PMID- 27688695
TI  - The incidence of possible causes of membranoproliferative glomerulonephritis: a
      single-center experience.
AB  - BACKGROUND: Diagnosis of membranoproliferative glomerulonephritis (MPGN) is based
      on kidney biopsy findings: unique glomerular injury pattern and characteristic
      changes on light, electron microscopy and immunohistochemical analysis. The
      purpose of this study was to identify possible etiology and incidence of
      glomerular injury among patients with a diagnosed MPGN. MATERIALS AND METHODS: A
      retrospective analysis (years 2000-2014) of 81 clinical cases with a diagnosis of
      MPGN based on biopsy results was performed. Records were examined, and data about
      viral, bacterial infections, autoimmune and hematological diseases was collected.
      Test results of blood C3 and C4 factors of the complement system, and results of
      kidney biopsy immunohistochemical analysis were investigated. Statistical
      analysis was performed using Statistical Package for the Social Sciences and p
      value less than 0.05 was considered statistically significant. RESULTS: Study
      population consisted of 55 males (67.9%) and 26 females (32.1%). The average
      patients' age was 48.53 (standard deviation +/- 16.67) years. The identified
      etiology of MPGN was: idiopathic in 26 cases (32.10%), bacterial infections in 20
      cases (24.69%), viral hepatitis in 16 cases (19.75%), autoimmune diseases in 11
      cases (13.58%), and hematological diseases in eight cases (9.88%). Changes of the
      concentration of complement component C3 as well as component C4 were found;
      their concentration was decreased in 26 (32.1%) and 17 (20.99%) patients'
      respectively while concentration was within the normal range in 11 (13.58%) and
      19 (23.46%) patients respectively. Immunohistochemistry results revealed
      immunoglobulin (Ig) deposits: C3+/Ig+ was found in 47 (58.02%) cases, C3-/Ig+ was
      found in 16 (19.75%) cases and in six (7.41%) cases test was not performed. The
      total number of immunoglobulin positive biopsies (C3+/Ig+ and C3-/Ig+, also
      called immune-complex mediated MPGN) was 63 (77.78%). Complement-mediated MPGN
      (C3+/Ig-) was less common and was diagnosed only in seven cases (8.64%). C3-/Ig-
      was found in five cases (6.17%). CONCLUSIONS: The leading cause of MPGN was
      idiopathic as well as bacterial infections. Complement component C3 concentration
      was mostly decreased. The incidence of normal and decreased concentration of the
      complement component C4 was almost equal. Most immunohistochemical deposits in
      kidney biopsy appeared to be C3/Ig positive, and it was observed in more than
      half of the cases of each MPGN etiological group. Hippokratia 2015; 19 (4): 314
      318.

PMID- 27688696
TI  - The analgesic effect of apelin-13 and its mechanism of action within the nitric
      oxide and serotonin pathways.
AB  - BACKGROUND: Apelin has various effects on a lot of systems such as central
      nervous system and cardiovascular system. This study investigated the possible
      analgesic effects of apelin-13 using the hot-plate and the tail-flick thermal
      analgesia tests in rats. We also evaluated the mechanism underlying the analgesic
      effects of apelin-13 by pretreating with Nw-nitro-L-arginine methyl ester (L
      NAME) or ondansetron. MATERIAL & METHODS: Forty male rats were used. The rats
      were randomly assigned to five groups according to the treatment received: Group
      I: Control; Group II: Morphine; Group III: Apelin-13; Group IV: Apelin-13+L-NAME;
      Group V: Apelin-13+Ondansetron. Acute thermal pain was modeled using the hot
      plate and the tail-flick tests. RESULTS: During the hot-plate test, i.p. Morphine
      and apelin-13 administered at zero- and 30 min produced significantly greater
      analgesic effects compared to the control. When the nitric oxide pathway was
      inhibited by administration of L-NAME with apelin-13, the analgesic effect
      continued. When apelin-13 and ondansetron were co-administered, the analgesic
      effect of apelin-13 disappeared at zero- and 30 min. During the tail-flick test,
      at 30 min, significantly higher levels of analgesia were observed in both the
      morphine and apelin group (which did not differ from each other) compared to the
      control group. L-NAME co-administered with apelin-13 did not affect the degree of
      analgesia, but apelin-13 co-administered with ondansetron was associated with a
      greater reduction in analgesia compared to the other groups. CONCLUSION: Our
      results demonstrate that apelin-13 exerts an analgesic effect; co-administration
      of apelin-13 and ondansetron inhibits antinociception, an effect apparently
      mediated by five-hydroxytryptamine-three (5-HT3) receptors. Hippokratia 2015; 19
      (4): 319-323.

PMID- 27688697
TI  - Bioimpedance spectroscopy method to determine hypervolemia in maintenance
      hemodialysis patients.
AB  - BACKGROUND: Hypervolemia is a major risk factor for hypertension leading to
      cardiovascular diseases and also a frequent problem in maintenance hemodialysis
      (MHD) patients. Fluid overload (FO) can be determined by bioimpedance
      spectroscopy (BIS) which is a new, practical, and non-invasive method. We tried
      to determine FO by BIS in MHD patients and find out the relationship between FO
      and clinical features. MATERIAL AND METHODS: We studied 100 MHD patients aged
      between 20 and 85 years and undergoing hemodialysis three times weekly for
      minimum one year. By using BIS, we estimated FO and extracellular water (ECW).
      The patients who exhibited a FO/ECW ratio >15% were considered as FO. RESULTS:
      Twenty-nine (29.0%) patients had a FO/ECW ratio >15%. In the overhydrated group,
      the mean pre-hemodialysis systolic blood pressure was 153.3 +/- 20.0 mmHg and the
      mean diastolic blood pressure was 89.1 +/- 8.5 mmHg. These were significantly
      higher than in the non-overhydrated group (113.5 +/- 14.5 and 71.0 +/- 8.8, p
      <0.001). FO was significantly correlated with systolic and diastolic blood
      pressures (r =0.63, p <0.001 and r =0.59, p <0.001). The patients were divided
      into two groups, i.e. those with cardiothoracic index (CTI) of  >0.5 and those
      with CTI of <=0.5. The median FO/ECW ratio was 0.11 L in the former group and
      0.08 L in the latter group with a significant difference (p =0.006). CONCLUSIONS:
      Hypervolemia is associated with high blood pressure and left ventricular
      hypertrophy that should be treated effectively to prevent cardiovascular diseases
      in MHD patients. BIS is useful to assess hydration status in MHD patients.
      Hippokratia 2015; 19 (4): 324-331.

PMID- 27688698
TI  - Proton pump inhibitors and statins: a possible interaction that favors low
      density lipoprotein cholesterol reduction?
AB  - BACKGROUND: Proton pump inhibitors (PPIs) might influence the metabolism of
      cholesterol and statins in the liver. AIM: The impact of PPIs on low-density
      lipoprotein cholesterol (LDL-C) levels in statin-treated patients. METHODS:
      Retrospective observational study including consecutive statin-treated
      individuals followed for >=3 years in a university hospital lipid clinic.
      Demographic characteristics as well as clinical and laboratory data were recorded
      at baseline and the most recent visit. High, moderate and low-intensity statin
      therapy was defined according to the expected LDL-C reduction (>=50%, 30-50%, and
      <30%, respectively). We compared the LDL-C reduction in subjects receiving statin
      + PPI with those on statin alone and assessed the overall effect of PPI
      administration on LDL-C lowering. RESULTS: Of 648 statin-treated subjects, 7%
      were also taking a PPI. There was no difference between PPI vs. non-PPI group
      regarding baseline characteristics and intensity of lipid-lowering therapy.
      Stepwise linear regression analysis showed that PPI use was significantly
      associated with LDL-C reduction (b =0.104, p =0.005) along with baseline LDL-C
      levels (b =0.482, p <0.001), treatment with ezetimibe (b =0.198, p <0.001),
      presence of diabetes (b =0.168, p <0.001), compliance with treatment (b =0.205, p
      <0.001), intensity of statin treatment (b =0.101, p =0.005) and cardiovascular
      risk (b =0.082, p =0.049). Subjects receiving statin + PPI had a higher LDL-C
      reduction by 6.4% compared with those taking a statin alone (fully adjusted p
      =0.005). CONCLUSIONS: PPIs may modestly boost the statin-mediated LDL-C
      reduction. This effect should be confirmed by prospective clinical studies.
      Hippokratia 2015; 19 (4): 332-337.

PMID- 27688699
TI  - Sudden unexpected death in epilepsy: experience from a tertiary epilepsy centre
      in Cyprus with review of the literature.
AB  - BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) affects 0.09-9.3 per
      1,000 person-years depending on the population studied and constitutes the most
      common cause of death in people with epilepsy. The purpose of this study was to
      analyze epidemiological data of patients with SUDEP, identify possible risk
      factors in the population of a tertiary referral center and provide a review of
      the literature aiming to raise awareness of this phenomenon. METHODS: Data for
      this study originate from the records of the Cyprus Institute of Neurology and
      Genetics in Nicosia Cyprus. We performed a systematic review of patients with
      epilepsy who had died between 1997 and 2012 and identified those whose death
      circumstances met the definition of SUDEP. Information was collected regarding
      sex, age, type of seizures, anti-epileptic therapies, and circumstances of death.
      Ethical approval was obtained from the institutional medical ethics committee.
      RESULTS: Four hundred and forty four new patients were diagnosed with epilepsy
      among referrals to the epilepsy clinic and were followed to the end of the study
      period. Seven patients, six males, were identified who met criteria for SUDEP.
      The average age was 30 years. All patients had had either primary or secondary
      tonic-clonic seizures. Most were on polypharmacy, and two had Vagus Nerve
      Stimulation implanted. Most deaths were unwitnessed and nocturnal. The overall
      incidence rate for SUDEP in this population was 2.13 deaths/1000 person-years.
      Overall Cumulative Incidence (or lifetime risk) was calculated at 15.76 SUDEP
      deaths/1,000 patients. CONCLUSIONS: In our series, SUDEP was primarily a
      nocturnal and unwitnessed event that affected primarily young males. Among both
      males and females patients, 36.8% of all deaths were due to SUDEP. The major risk
      factor identified was the occurrence of generalized tonic-clonic seizures
      signifying that every effort should be made to control this type of seizures.
      Hippokratia 2015; 19 (4): 338-343.

PMID- 27688700
TI  - Peripheral blood monocytes can differentiate into efficient insulin-producing
      cells in vitro.
AB  - BACKGROUND: Recent studies provide evidence that peripheral blood monocytes have
      the ability to differentiate into mesenchymal-like cells. The ability of cultured
      monocytes to differentiate and produce insulin in vitro is analysed in the
      present study. METHODS: Peripheral blood monocytes were isolated from healthy
      donors and cultivated for fourteen days. Growth factors and liraglutide were used
      to induce pancreatic differentiation in most of the cultures. The growth factors
      were: monocyte colony-stimulating factor, interleukin-3, hepatocyte growth factor
      and epidermal growth factor. The rest of the cultures were cultivated only with
      nutrient medium and human serum. Insulin levels were measured by an enzyme-linked
      immunosorbent assay. Cellular morphology was observed using optical and electron
      microscopy. Cell membrane receptors were detected by flow cytometry. RESULTS:
      Monocytes were able to synthesize and excrete high levels of insulin after seven
      days in culture. A further increase in the excretion of insulin was observed
      after fourteen days. Cells were also able to differentiate and synthesize
      insulin, even if no growth factors were added to the culture medium. Some of the
      cultures were able to excrete insulin in a glucose-dependent manner.
      Differentiated monocytes were connected to neighbouring cells with axons and
      resembled the morphology of mesenchymal, dendritic and myeloid-progenitor cells.
      Cells retained their mature receptors and simultaneously developed immature
      receptors on their membrane. CONCLUSIONS: Monocytes can acquire morphological
      properties of multipotent cells when they are cultivated under specific
      conditions in vitro. Differentiated monocytes are able to synthesize and excrete
      insulin. Hippokratia 2015; 19 (4): 344-351.

PMID- 27688701
TI  - A novel surgical tool for the revision hip arthroplasty due to neck stem's
      fracture.
AB  - During revision surgery of total hip arthroplasties, surgeons may come across the
      challenging complication of a proximally fractured femoral stem, which however
      maintains sufficient distal fixation. Such cases, although rare, are extremely
      demanding due to lack of available attachments that would assist surgical
      explantation of the broken implant. It is herein presented a metal sterilisable
      surgical tool designed for the removal of the femoral stem broken at the level of
      the "neck". Hippokratia 2015; 19 (4): 352-355. 

PMID- 27688702
TI  - Evaluation and management of juvenile recurrent parotitis in children from
      northern Greece.
AB  - BACKGROUND: Juvenile Recurrent Parotitis (JRP) is a recurrent parotid
      inflammation of childhood.  The aim of our study was to investigate the clinical,
      laboratory and imaging profile of children with JRP as well as to estimate the
      impact of siadendoscopy as a therapeutic tool in the clinical outcome of JRP.
      METHODS: Twenty-three children with JRP aged 3.5-16 years, were investigated.
      Twelve of them underwent sialendoscopy: seven aged <8 years under general and
      five aged >8 years under local anesthesia. RESULTS: The age at onset ranged from
      2-15 years while the number of episodes from 2-8 per year. The autoantibody
      profile was negative in all patients, suggesting no evidence for autoimmune
      diseases.  Antibody deficiency was found in two children. The imaging studies
      reveal an overall parotid swelling and intraparotid lymph nodes while
      microabscesses were present in 31% of the patients. Twelve patients who underwent
      sialendoscopy had a significant improvement in their clinical outcome; the mean
      episodes of JRP before sialendoscopy was 3.9/year and reduced to 0.4 at the post
      intervention year. CONCLUSION: Sialendoscopy represents an alternative and
      promising perspective in the management of JRP. Hippokratia 2015; 19 (4): 356
      359.

PMID- 27688703
TI  - Analysis of Peristaltic Motion of a Nanofluid with Wall Shear Stress,
      Microrotation, and Thermal Radiation Effects.
AB  - This paper analyzes the peristaltic flow of an incompressible micropolar
      nanofluid in a tapered asymmetric channel in the presence of thermal radiation
      and heat sources parameters. The rotation of the nanoparticles is incorporated in
      the flow model. The equations governing the nanofluid flow are modeled and exact
      solutions are managed under long wavelength and flow Reynolds number and long
      wavelength approximations. Explicit expressions of axial velocity, stream
      function, microrotation, nanoparticle temperature, and concentration have been
      derived. The phenomena of shear stress and trapping have also been discussed.
      Finally, the influences of various parameters of interest on flow variables have
      been discussed numerically and explained graphically. Besides, the results
      obtained in this paper will be helpful to those who are working on the
      development of various realms like fluid mechanics, the rotation, Brownian
      motion, thermophoresis, coupling number, micropolar parameter, and the
      nondimensional geometry parameters. 

PMID- 27688704
TI  - Archival Collections are Important in the Study of the Biology, Diversity, and
      Evolution of Arboviruses.
AB  - Historically, classifications of arboviruses were based on serological
      techniques. Hence, collections of arbovirus isolates have been central to this
      process by providing the antigenic reagents for these methods. However, with
      increasing concern about biosafety and security, the introduction of molecular
      biology techniques has led to greater emphasis on the storage of nucleic acid
      sequence data over the maintenance of archival material. In this commentary, we
      provide examples of where archival collections provide an important source of
      genetic material to assist in confirming the authenticity of reference strains
      and vaccine stocks, to clarify taxonomic relationships particularly when isolates
      of the same virus species have been collected across a wide expanse of time and
      space, for future phenotypic analysis, to determine the historical diversity of
      strains, and to understand the mechanisms leading to changes in genome structure
      and virus evolution. 

PMID- 27688705
TI  - LPS-induced expression of CD14 in the TRIF pathway is epigenetically regulated by
      sulforaphane in porcine pulmonary alveolar macrophages.
AB  - Pulmonary alveolar macrophages (AMs) are important in defense against bacterial
      lung inflammation. Cluster of differentiation 14 (CD14) is involved in
      recognizing bacterial lipopolysaccharide (LPS) through MyD88-dependent and TRIF
      pathways of innate immunity. Sulforaphane (SFN) shows anti-inflammatory activity
      and suppresses DNA methylation. To identify CD14 epigenetic changes by SFN in the
      LPS-induced TRIF pathway, an AMs model was investigated in vitro. CD14 gene
      expression was induced by 5 ug/ml LPS at the time point of 12 h and suppressed by
      5 uM SFN. After 12 h of LPS stimulation, gene expression was significantly up
      regulated, including TRIF, TRAF6, NF-kappaB, TRAF3, IRF7, TNF-alpha, IL-1beta, IL
      6, and IFN-beta. LPS-induced TRAM, TRIF, RIPK1, TRAF3, TNF-alpha, IL-1beta and
      IFN-beta were suppressed by 5 uM SFN. Similarly, DNMT3a expression was increased
      by LPS but significantly down-regulated by 5 uM SFN. It showed positive
      correlation of CD14 gene body methylation with in LPS-stimulated AMs, and this
      methylation status was inhibited by SFN. This study suggests that SFN suppresses
      CD14 activation in bacterial inflammation through epigenetic regulation of CD14
      gene body methylation associated with DNMT3a. The results provide insights into
      SFN-mediated epigenetic down-regulation of CD14 in LPS-induced TRIF pathway
      inflammation and may lead to new methods for controlling LPS-induced inflammation
      in pigs.

PMID- 27688706
TI  - Identifying Significant Features in Cancer Methylation Data Using Gene Pathway
      Segmentation.
AB  - In order to provide the most effective therapy for cancer, it is important to be
      able to diagnose whether a patient's cancer will respond to a proposed treatment.
      Methylation profiling could contain information from which such predictions could
      be made. Currently, hypothesis testing is used to determine whether possible
      biomarkers for cancer progression produce statistically significant results.
      However, this approach requires the identification of individual genes, or sets
      of genes, as candidate hypotheses, and with the increasing size of modern
      microarrays, this task is becoming progressively harder. Exhaustive testing of
      small sets of genes is computationally infeasible, and so hypothesis generation
      depends either on the use of established biological knowledge or on heuristic
      methods. As an alternative machine learning, methods can be used to identify
      groups of genes that are acting together within sets of cancer data and associate
      their behaviors with cancer progression. These methods have the advantage of
      being multivariate and unbiased but unfortunately also rapidly become
      computationally infeasible as the number of gene probes and datasets increases.
      To address this problem, we have investigated a way of utilizing prior knowledge
      to segment microarray datasets in such a way that machine learning can be used to
      identify candidate sets of genes for hypothesis testing. A methylation dataset is
      divided into subsets, where each subset contains only the probes that relate to a
      known gene pathway. Each of these pathway subsets is used independently for
      classification. The classification method is AdaBoost with decision trees as weak
      classifiers. Since each pathway subset contains a relatively small number of gene
      probes, it is possible to train and test its classification accuracy quickly and
      determine whether it has valuable diagnostic information. Finally, genes from
      successful pathway subsets can be combined to create a classifier of high
      accuracy. 

PMID- 27688707
TI  - Novel Biomarker Candidates for Colorectal Cancer Metastasis: A Meta-analysis of
      In Vitro Studies.
AB  - Colorectal cancer (CRC) is one of the most common and lethal cancers. Although
      numerous studies have evaluated potential biomarkers for early diagnosis, current
      biomarkers have failed to reach an acceptable level of accuracy for distant
      metastasis. In this paper, we performed a gene set meta-analysis of in vitro
      microarray studies and combined the results from this study with previously
      published proteomic data to validate and suggest prognostic candidates for CRC
      metastasis. Two microarray data sets included found 21 significant genes. Of
      these significant genes, ALDOA, IL8 (CXCL8), and PARP4 had strong potential as
      prognostic candidates. LAMB2, MCM7, CXCL23A, SERPINA3, ABCA3, ALDH3A2, and POLR2I
      also have potential. Other candidates were more controversial, possibly because
      of the biologic heterogeneity of tumor cells, which is a major obstacle to
      predicting metastasis. In conclusion, we demonstrated a meta-analysis approach
      and successfully suggested ten biomarker candidates for future investigation. 

PMID- 27688708
TI  - DNA Methylation Heterogeneity Patterns in Breast Cancer Cell Lines.
AB  - Heterogeneous DNA methylation patterns are linked to tumor growth. In order to
      study DNA methylation heterogeneity patterns for breast cancer cell lines, we
      comparatively study four metrics: variance, I (2) statistic, entropy, and
      methylation state. Using the categorical metric methylation state, we select the
      two most heterogeneous states to identify genes that directly affect tumor
      suppressor genes and high- or moderate-risk breast cancer genes. Utilizing the
      Gene Set Enrichment Analysis software and the ConsensusPath Database
      visualization tool, we generate integrated gene networks to study biological
      relations of heterogeneous genes. This analysis has allowed us to contribute 19
      potential breast cancer biomarker genes to cancer databases by locating "hub
      genes" - heterogeneous genes of significant biological interactions, selected
      from numerous cancer modules. We have discovered a considerable relationship
      between these hub genes and heterogeneously methylated oncogenes. Our results
      have many implications for further heterogeneity analyses of methylation patterns
      and early detection of breast cancer susceptibility. 

PMID- 27688709
TI  - Evolution of Synonymous Codon Usage in the Mitogenomes of Certain Species of
      Bilaterian Lineage with Special Reference to Chaetognatha.
AB  - Chaetognatha is a minor phylum, comprising transparent marine invertebrates
      varying in size from 0.5 to 12 cm. The exact phylogenetic position of
      Chaetognatha in Metazoa has not been deciphered as some embryological
      characteristics place chaetognaths among deuterostomes and some morphological
      characteristics place these among protostomes. In this study, the major factors
      that drive synonymous codon usage bias (SCUB) in the mitogenomes of
      representative species of Chaetognatha and chosen species of other closely
      related phyla were analyzed. Spearman's rank correlation analyses of nucleotide
      contents suggested that mutational pressure and selection were acting in all
      examined mitogenomes but with varying intensities. The quantification of SCUB
      using effective number of codons vs. GC composition at the third codon position
      (GC3) plot suggested that mutational pressure due to GC compositional constraints
      might be one of the major influencing forces driving the SCUB in all chaetognaths
      except Sagitta enflata. However, neutrality plots revealed no significant
      correlation between GC3 and cumulative GC content at first and second codon
      positions (GC12) in all other species, except in Daphnia pulex. The parity rule 2
      bias plot showed that significant compositional differences existed between C and
      G, as well as between A and T, contents in most of the protein-coding genes
      (PCGs) and, comparatively, A and T contents were used more proportionally than C
      and G contents in all chosen mitogenomes. Chi-square analysis revealed the
      presence of putative optimal codons in all species, except in S. enflata. The
      correspondence analysis identified that mutational pressure and selection act on
      the mitogenomes of the selected chaetognaths and other phyla with varying
      intensities. The cluster analysis based on relative synonymous codon usage (RSCU)
      values revealed that RSCU variations in the PCGs of mitogenomes of chaetognaths
      are more comparable with those of protostomes. Apart from mutational pressure and
      selection, certain unknown selective forces might be acting on the PCGs in the
      analyzed mitogenomes as the phenomenon of SCUB could not be explained by
      mutational pressure, by selection, or by both. 

PMID- 27688710
TI  - A Single-Cell Platform for Monitoring Viral Proteolytic Cleavage in Different
      Cellular Compartments.
AB  - Infectious diseases affect human health despite advances in biomedical research
      and drug discovery. Among these, viruses are especially difficult to tackle due
      to the sudden transfer from animals to humans, high mutational rates, resistance
      to current treatments, and the intricacies of their molecular interactions with
      the host. As an example of these interactions, we describe a cell-based approach
      to monitor specific proteolytic events executed by either the viral-encoded
      protease or by host proteins on the virus. We then emphasize the significance of
      examining proteolysis within the subcellular compartment where cleavage occurs
      naturally. We show the power of stable expression, highlighting the usefulness of
      the cell-based multiplexed approach, which we have adapted to two independent
      assays previously developed to monitor (a) the activity of the HIV-1-encoded
      protease or (b) the cleavage of the HIV-1-encoded envelope protein by the host.
      Multiplexing was achieved by mixing cells each carrying a different assay or,
      alternatively, by engineering cells expressing two assays. Multiplexing relies on
      the robustness of the individual assays and their clear discrimination, further
      enhancing screening capabilities in an attempt to block proteolytic events
      required for viral infectivity and spread. 

PMID- 27688711
TI  - Vitamin D Deficiency in Medical Inpatients: A Retrospective Study of Implications
      of Untreated Versus Treated Deficiency.
AB  - Vitamin D deficiency and insufficiency may further increase fracture risk in
      patients with decreased bone mineral density. A cross-sectional study on serum
      vitamin D concentrations in medical inpatients was conducted at Bassetlaw
      District General Hospital between April 2014 and January 2015 (10 months), and
      the relationship of serum vitamin D concentrations with calcium and alkaline
      phosphatase was evaluated. 25-Hydroxyvitamin D immunoassays were used and
      analyzed in the local laboratory. The total number of patients analyzed was 200,
      age range 18-99 years, with mean age of 76 years. The most common presentation
      was found to be fall/collapse. The following cutoff points for serum vitamin D
      were used: levels <=30 nmol/L for severe deficiency, >30-50 nmol/L for moderate
      deficiency, >50-75 nmol/L for mild deficiency, and anything above 75 nmol/L as
      normal. Of the 209 participants examined, 78 (37.3%) participants had mild
      vitamin D deficiency, 54 (25.8%) participants had moderate vitamin D deficiency,
      68 (32.5%) participants had severe vitamin D deficiency, and 9 (4.3%)
      participants with low vitamin D levels died during their admission. Of the 122
      moderate/severe patients, 70 (57.4%) patients had their vitamin D deficiency
      treated, according to local Trust guidelines. The study found no relationship
      between serum calcium levels and vitamin D deficiency, whereas patients' alkaline
      phosphatase levels were found to be higher with increased severity of vitamin D
      deficiency. The study examined the implications of untreated severe/moderate
      vitamin D deficiency compared to treated deficiency, in terms of the frequency of
      readmission with similar complaints. It was found that the rate of readmission
      within one year in patients who were not treated was 57%, compared to 48% in
      patients whose vitamin D deficiency was treated. Presenting after falls was a
      recurring theme. It was concluded that even if moderate vitamin D deficiency can
      be asymptomatic, it is important to correct it as it can have an impact on
      morbidity and readmission rates in the long term. 

PMID- 27688712
TI  - Standardized Follow-up of Patients with Symptomatic Knee Osteoarthritis Treated
      with a Single Intra-articular Injection of a Combination of Cross-Linked
      Hyaluronic Acid and Mannitol.
AB  - OBJECTIVES: The objective of this study is to obtain pilot data from daily
      practice conditions of a viscosupplement made of a cross-linked high-molecular
      weight hyaluronic acid (HA) combined with mannitol in patients with knee
      osteoarthritis (KOA). METHODS: The data of 40 consecutive patients, 29 women and
      11 men, who were prospectively followed up for 6 months, using a standardized
      procedure, were retrospectively analyzed. All patients have received a single
      intra-articular injection of HAnox-M-XL (4.4 mL), viscosupplement made of a cross
      linked HA (16 mg/mL) + mannitol (35 mg/mL), in the target knee. The primary
      outcome was safety. The secondary end points included 3- and 6-month change in
      the WOMAC pain (0-50) and WOMAC total (0-240) and patient's global assessment
      (PGA). Patient's self-assessment of treatment efficacy (0-3) and analgesic
      consumption were obtained at months 3 and 6. An intent-to-treat analysis was
      performed. RESULTS: Mean (SD) age was 60.7 (13.9) years, and mean BMI was 28.6
      (5.0). Kellgren-Lawrence radiological grade was I/II and III/IV in 13 and 27 of
      the subjects, respectively. The average WOMAC pain and WOMAC total scores at
      baseline were 21.5 (9.8) and 89.9 (42.8), respectively. Thirty-nine patients
      completed the follow-up. HAnox-M-XL was well tolerated; two patients experienced
      knee pain after injection, which resolved within three days. No treatment-related
      severe adverse event was reported. Mean (SD) variations in WOMAC pain and WOMAC
      total scores were -8.2 (8.9) and -38.4 (35.6), respectively, at month 6 (P =
      0.001). PGA decreased from 5.5 (2.0) to 3.0 (2.2) (P = 0.006). Efficacy was rated
      as good or very good in 76.9% of the cases. Most of the regular analgesics users
      decreased their consumption. CONCLUSION: Treatment with one injection of 4.4 mL
      HAnox-M-XL is effective to alleviate KOA symptoms over six months, without safety
      concern. Controlled trials are needed to confirm these pilot data.

PMID- 27688714
TI  - Moving Medicine, Moving Minds: Helping Developing Countries Overcome Barriers to
      Outsourcing Health Commodity Distribution to Boost Supply Chain Performance and
      Strengthen Health Systems.

PMID- 27688713
TI  - Effective LARC Providers: Moving Beyond Training (Republication).

PMID- 27688715
TI  - Using Qualitative Methods to Validate and Contextualize Quantitative Findings: A
      Case Study of Research on Sexual Behavior and Gender-Based Violence Among Young
      Swazi Women.

PMID- 27688716
TI  - Successful Implementation of a Multicountry Clinical Surveillance and Data
      Collection System for Ebola Virus Disease in West Africa: Findings and Lessons
      Learned.
AB  - BACKGROUND: The 2014 outbreak of Ebola virus disease (EVD) in West Africa was the
      largest ever recorded. Starting in September 2014, International Medical Corps
      (IMC) managed 5 Ebola treatment units (ETUs) in Liberia and Sierra Leone, which
      cumulatively cared for about 2,500 patients. We conducted a retrospective cohort
      study of patient data collected at the 5 ETUs over 1 year of operations. METHODS:
      To collect clinical and epidemiological data from the patient care areas, each
      chart was either manually copied across the fence between the high-risk zone and
      low-risk zone, imaged across the fence, or imaged in the high-risk zone. Each
      ETU's data were entered into a separate electronic database, and these were later
      combined into a single relational database. Lot quality assurance sampling was
      used to ensure data quality, with reentry of data with high error rates from
      imaged records. RESULTS: The IMC database contains records on 2,768 patient
      presentations, including 2,351 patient admissions with full follow-up data. Of
      the patients admitted, 470 (20.0%) tested positive for EVD, with an overall case
      fatality ratio (CFR) of 57.0% for EVD-positive patients and 8.1% for EVD-negative
      patients. Although more men were admitted than women (53.4% vs. 46.6%), a larger
      proportion of women were diagnosed EVD positive (25.6% vs. 15.2%). Diarrhea, red
      eyes, contact with an ill person, and funeral attendance were significantly more
      common in patients with EVD than in those with other diagnoses. Among EVD
      positive patients, age was a significant predictor of mortality: the highest CFRs
      were among children under 5 (89.1%) and adults over 55 (71.4%). DISCUSSION: While
      several prior reports have documented the experiences of individual ETUs, this
      study is the first to present data from multiple ETUs across 2 countries run by
      the same organization with similar clinical protocols. Our experience
      demonstrates that even in austere settings under difficult conditions, it is
      possible for humanitarian organizations to collect high-quality clinical and
      epidemiologic data during a major infectious disease outbreak.

PMID- 27688717
TI  - Intensive Group Learning and On-Site Services to Improve Sexual and Reproductive
      Health Among Young Adults in Liberia: A Randomized Evaluation of HealthyActions.
AB  - INTRODUCTION: Young Liberians, particularly undereducated young adults, face
      substantial sexual and reproductive health (SRH) challenges, with low uptake of
      contraceptive methods, high rates of unintended pregnancy, and low levels of
      knowledge about HIV status. The purpose of this study was to assess the impact of
      a 6-day intensive group learning intervention combined with on-site SRH services
      (called HealthyActions) among out-of-school young adults, implemented through an
      existing alternative education program, on uptake of contraception and HIV
      testing and counseling (HTC). METHODS: The intervention was implemented among
      young women and men ages 15-35 who were enrolled in alternative basic education
      learning sites in 5 counties of Liberia. We conducted a randomized evaluation to
      assess program impact. Baseline data were collected in January-March 2014, and
      endline data in June-July 2014. Key outcomes of condom use, contraceptive use,
      and HTC were estimated with difference-in-difference models using fixed effects.
      All analyses were conducted in Stata 13. RESULTS: We assessed outcomes for 1,157
      learners at baseline and 1,052 learners at endline, across 29 treatment and 26
      control sites. After adjusting for potential confounders, learners in the
      HealthyActions intervention group were 12% less likely to report never using a
      condom with a regular partner over the last month compared with the control group
      (P = .02). Female learners who received HealthyActions were 13% more likely to
      use any form of modern contraception compared with learners in control sites
      (P<.001), with the greatest increase in the use of contraceptive implants.
      Learners in HealthyActions sites were 45% more likely to have received HTC
      (P<.001). CONCLUSION: Providing intensive group learning in a supportive
      environment coupled with on-site health services improved SRH outcomes among
      participating learners. The focus of HealthyActions on participatory learning for
      low-literacy populations presents an adaptable solution for health programming
      across Liberia and the region.

PMID- 27688718
TI  - Progress in Harmonizing Tiered HIV Laboratory Systems: Challenges and
      Opportunities in 8 African Countries.
AB  - In 2014, the Joint United Nations Programme on HIV/AIDS released its 90-90-90
      targets, which make laboratory diagnostics a cornerstone for measuring efforts
      toward the epidemic control of HIV. A data-driven laboratory harmonization and
      standardization approach is one way to create efficiencies and ensure optimal
      laboratory procurements. Following the 2008 "Maputo Declaration on Strengthening
      of Laboratory Systems"-a call for government leadership in harmonizing tiered
      laboratory networks and standardizing testing services-several national
      ministries of health requested that the United States Government and in-country
      partners help implement the recommendations by facilitating laboratory
      harmonization and standardization workshops, with a primary focus on improving
      HIV laboratory service delivery. Between 2007 and 2015, harmonization and
      standardization workshops were held in 8 African countries. This article reviews
      progress in the harmonization of laboratory systems in these 8 countries. We
      examined agreed-upon instrument lists established at the workshops and compared
      them against instrument data from laboratory quantification exercises over time.
      We used this measure as an indicator of adherence to national procurement
      policies. We found high levels of diversity across laboratories' diagnostic
      instruments, equipment, and services. This diversity contributes to different
      levels of compliance with expected service delivery standards. We believe the
      following challenges to be the most important to address: (1) lack of adherence
      to procurement policies, (2) absence or limited influence of a coordinating body
      to fully implement harmonization proposals, and (3) misalignment of laboratory
      policies with minimum packages of care and with national HIV care and treatment
      guidelines. Overall, the effort to implement the recommendations from the Maputo
      Declaration has had mixed success and is a work in progress. Program managers
      should continue efforts to advance the principles outlined in the Maputo
      Declaration. Quantification exercises are an important method of identifying
      instrument diversity, and provide an opportunity to measure efforts toward
      standardization.

PMID- 27688719
TI  - Improving the Quality of Postabortion Care Services in Togo Increased Uptake of
      Contraception.
AB  - High-quality postabortion care (PAC) services that include family planning
      counseling and a full range of contraceptives at point of treatment for abortion
      complications have great potential to break the cycle of repeat unintended
      pregnancies and demand for abortions. We describe the first application of a
      systematic approach to quality improvement of PAC services in a West African
      country. This approach-IntraHealth International's Optimizing Performance and
      Quality (OPQ) approach-was applied at 5 health care facilities in Togo starting
      in November 2014. A baseline assessment identified the following needs:
      reorganizing services to ensure that contraceptives are provided at point of
      treatment for abortion complications, before PAC clients are discharged;
      improving provider competencies in family planning services, including in
      providing long-acting reversible contraceptive implants and intrauterine devices;
      ensuring that contraceptive methods are available to all PAC clients free of
      charge; standardizing PAC registers and enhancing data collection and reporting
      systems; enhancing internal supervision systems at facilities and teamwork among
      PAC providers; and engaging PAC providers in community talks. Solutions devised
      and applied at the facilities during OPQ resulted in significant increases in
      contraceptive counseling and uptake among PAC clients: During the 5-month
      baseline period, 31% of PAC clients were counseled, while during the 13-month
      intervention period, 91% were counseled. Of all PAC clients counseled during the
      baseline period, 37% accepted a contraceptive, compared with 60% of those
      counseled during the intervention period. Oral contraceptive pills remained the
      most popular method during both periods, yet uptake of implants increased
      significantly during the intervention period-from 4% to 27% of those accepting
      contraceptives. This result demonstrates that the solutions applied maintained
      method choice while expanding access to underused long-acting reversible
      contraceptives. OPQ shows great potential for sustainability and scale in Togo
      and for application in similar contexts where the health system struggles to
      offer safe, high-quality, accessible PAC services.

PMID- 27688720
TI  - Use of the World Health Organization's Medical Eligibility Criteria for
      Contraceptive Use Guidance in sub-Saharan African Countries: A Cross-Sectional
      Study.
AB  - Given recent updates to the postpartum contraception recommendations in the fifth
      edition of the Medical Eligibility Criteria for Contraceptive Use (MEC),
      published by the World Health Organization (WHO), the purpose of this qualitative
      study was to assess the extent to which national family planning policies in sub
      Saharan African countries are in agreement with the WHO MEC, particularly with
      regard to postpartum contraceptive use. WHO headquarters sent questionnaires to
      country-level focal points to complete with their Ministry of Health
      counterparts. Between February and May 2016, 23 of 32 (72%) surveys were
      completed. All respondents reported that their countries had used the MEC
      document in the past, with most reporting that they had used the guidance as a
      reference (n = 20, 87%), for training purposes (n = 19, 83%), to change clinical
      practices (n = 17, 74%), and to develop national policies (n = 16, 70%). While
      many respondents (16, 70%) indicated their countries already include immediate
      postpartum intrauterine device insertion among breastfeeding women in their
      family planning policies, few reported currently allowing use of progestogen-only
      pills (n = 8, 35%) or implants (n = 8, 35%) during the immediate postpartum
      period (i.e., less than 48 hours after delivery) for breastfeeding women. A
      higher percentage of respondents indicated their countries allowed breastfeeding
      women the option of progestogen-only pills (n = 16, 70%) and implants (n = 13,
      57%) between 48 hours and 6 weeks postpartum. Findings from this baseline
      assessment suggest that many countries may benefit from training and policy
      formulation support to adapt both new WHO MEC updates as well as existing
      recommendations from previous MEC revisions into national family planning
      guidelines.

PMID- 27688721
TI  - Notch signalling pathway as an oncogenic factor involved in cancer development.
AB  - Notch signalling is an evolutionarily conserved signalling pathway, which plays a
      significant role in a wide array of cellular processes including proliferation,
      differentiation, and apoptosis. Nevertheless, it must be noted that Notch is a
      binary cell fate determinant, and its overexpression has been described as
      oncogenic in a broad range of human malignancies. This finding led to interest in
      therapeutically targeting this pathway especially by the use of GSIs, which block
      the cleavage of Notch at the cell membrane and inhibit release of the
      transcriptionally active NotchIC subunit. Preclinical cancer models have clearly
      demonstrated that GSIs suppress the growth of such malignancies as pancreatic,
      breast, and lung cancer; however, GSI treatment in vivo is associated with side
      effects, especially those within the gastrointestinal tract. Although intensive
      studies are associated with the role of gamma-secretase in pathological states,
      it should be pointed out that this complex impacts on proteolytic cleavages of
      around 55 membrane proteins. Therefore, it is clear that GSIs are highly non
      specific and additional drugs must be designed, which will more specifically
      target components of the Notch signalling. 

PMID- 27688724
TI  - Radiation-induced caries as the late effect of radiation therapy in the head and
      neck region.
AB  - Overall improvement in the nationwide system of medical services has consequently
      boosted the number of successfully treated patients who suffer from head and neck
      cancer. It is essential to effectively prevent development of radiation-induced
      caries as the late effect of radiation therapy. Incidence and severity of
      radiationinduced changes within the teeth individually vary depending on the
      patient's age, actual radiation dose, size of radiation exposure field, patient's
      general condition and additional risk factors. Inadequately managed treatment of
      caries may lead to loss of teeth, as well as prove instrumental in tangibly
      diminishing individual quality of life in patients. Furthermore, the need to have
      the teeth deemed unyielding or unsuitable for the application of conservative
      methods of treatment duly extracted is fraught for a patient with an extra hazard
      of developing osteoradionecrosis (ORN), while also increasing all attendant
      therapeutic expenditures. The present paper aims to offer some practical insights
      into currently available methods of preventing likely development of radiation
      induced caries. 

PMID- 27688723
TI  - Particular aspects in the cytogenetics and molecular biology of salivary gland
      tumours - current review of reports.
AB  - Salivary gland tumours are a group of lesions whose heterogeneity of biological
      and pathological features is widely reflected in the molecular aspect. This is
      demonstrated by an increasing number of studies in the field of genetics of these
      tumours. The aim of this study was to collect the most significant scientific
      reports on the cytogenetic and molecular data concerning these tumours, which
      might facilitate the identification of potential biomarkers and therapeutic
      targets. The analysis covered 71 papers included in the PubMed database. We
      focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour,
      mucoepidermoid carcinoma, and others. The aim of this study is to present current
      knowledge about widely explored genotypic alterations (such as PLAG1 gene in
      pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about
      rare markers, like Mena or SOX10 protein, which might also be associated with
      tumourigenesis and carcinogenesis of these tumours. 

PMID- 27688725
TI  - Impact of mTOR expression on clinical outcome in paediatric patients with B-cell
      acute lymphoblastic leukaemia - preliminary report.
AB  - AIM OF THE STUDY: To characterise expression of mTOR (mammalian target of
      rapamycin) in childhood B-cell acute lymphoblastic leukaemia (ALL), and to
      evaluate a possible link between mTOR and clinical characteristics. MATERIAL AND
      METHODS: The examined group consisted of 21 consecutive patients, aged 1-18
      years, diagnosed with B-cell ALL in 2010, and 10 relapsed B-cell ALL patients
      diagnosed for the first time between 2009 and 2011, who developed relapse before
      2014. All subjects were treated in the Department of Paediatric Haematology and
      Oncology of the Medical University of Warsaw according to the ALL-IC BFM 2002
      Protocol. We evaluated mTOR and phospho-mTOR expression by immunohistochemistry
      using rabbit monoclonal antibodies. RESULTS: mTOR expression was found to be
      significantly associated with the risk of relapse and was more frequent in ALL
      recurrence. No significant relationship was detected between mTOR expression and
      other features of high-risk disease in paediatric ALL. CONCLUSIONS: mTOR activity
      could be considered a high-risk feature in paediatric B-cell ALL. Expression of
      mTOR kinase is observed remarkably more frequently in disease recurrence than at
      first diagnosis, indicating higher proliferative and survival potential of
      leukaemic cells in relapse. Routine analysis of mTOR activity could be performed
      to select patients that may potentially benefit from mTOR inhibitors (MTI)
      treatment.

PMID- 27688722
TI  - The potential therapeutic applications and prognostic significance of metastasis
      associated in colon cancer-1 (MACC1) in cancers.
AB  - The metastasis-associated in colon cancer-1 (MACC1) gene was identified in 2009.
      Expression of MACC1 was found to be significantly upregulated in primary and
      metastatic colon carcinomas compared to normal tissues or adenomas. The induction
      of MACC1 occurs at the crucial step of transition from a benign to a malignant
      phenotype. The aim of this review was to summarise current results of non
      clinical and clinical studies on the role of MACC1 in the carcinogenesis and
      progression of cancer, as well its potential therapeutic and prognostic
      significance. The gene encoding the HGF receptor MET is a transcriptional target
      of MACC1. In addition to promoting the proliferation, invasion, and migration of
      colon cancer cells in cell culture and tumour growth and metastasis in mouse
      models, MACC1 also contributes to carcinogenesis and progression of colorectal
      cancer through the beta-catenin signalling pathway and mesenchymal-epithelial
      transition. MACC1 knockdown with si/sh RNA was investigated in cell lines of
      different types of cancer. MACC1 is a promising therapeutic target for antitumour
      and antimetastatic intervention strategies for cancers. Here, it is presented as
      a potential independent prognostic indicator of reduced overall survival as well
      as of the occurrence of distant metastasis in patients with different types of
      cancer. 

PMID- 27688726
TI  - Primary mediastinal B-cell lymphoma - metabolic and anatomical features in 18FDG
      PET/CT and response to therapy.
AB  - AIM OF THE STUDY: Determining the role of PET/CT imaging in the evaluation of
      treatment efficacy in primary mediastinal B-cell lymphoma (PMBCL). MATERIAL AND
      METHODS: Retrospective analysis of seven PMBCL patients, treated at the
      University Hospital in Krakow, with interim PET/CT after the third course of
      chemo-immunotherapy.The analysis was based on the calculation of exact tumour
      volume and metabolic activity, compared with initial values (directly after
      diagnosis). RESULTS: Patients (five females, two males, average age 26.2 years,
      range 18-40 years), in clinical stage IIBX at diagnosis, were treated with eight
      cycles of R-CHOP-14 regimen, with radiotherapy consolidation (7/7) and central
      nervous system prophylaxis (6/7). The observed decrease in tumour volume between
      the initial staging and the interim PET ranged 72-89%. The mean DeltaSUVmax
      reduction between initial (when available) and interim PET was 87% (range 84
      89%). In 3/7 cases in the interim PET/CT, the uptake of the tumour was higher
      than the liver (Deauville Criteria score 4-5), and in 4/7 it was lower than the
      liver but higher than mediastinal blood pool structures (score 3 according to
      Deauville Criteria). After a median follow-up of 58 months - OS and EFS is 100%.
      CONCLUSIONS: The excellent clinical outcome in the study group corresponds with
      very good metabolic and volumetric response in the interim PET. The DeltaSUVmax
      seems to be easier in implementation and has a more significant impact than other
      measurements.

PMID- 27688727
TI  - Total antioxidant status in lung cancer is associated with levels of endogenous
      antioxidants and disease stage rather than lifestyle factors - preliminary study.
AB  - AIM OF THE STUDY: Decreased total antioxidant capacity (TAC) has been reported in
      different neoplasms, including lung cancer. However, no study concerning the
      relationship between endogenous antioxidants, lifestyle factors, and TAC has been
      conducted among lung cancer patients. The purpose of the study was to investigate
      the associations between endogenous antioxidants, severity of disease, lifestyle
      factors, and TAC in lung cancer patients. MATERIAL AND METHODS: The study was
      conducted among 59 lung cancer patients. The levels of total antioxidant status
      (ATBS method), endogenous antioxidants, and C-reactive protein were measured in
      patients' sera automatically. Dietary habits of the subjects were evaluated based
      on the Food Frequency Questionnaire (FFQ) on the day of admission to hospital.
      RESULTS: We found a positive correlation between serum albumin, uric acid (UA),
      and TAC and a negative correlation between CRP and TAC. Moreover, TAC was
      significantly positively associated with disease stage. We did not find any
      significant relationship between the frequency of selected food consumption and
      TAC in lung cancer patients, except for a positive correlation between the
      frequency of refined cereal products consumption and TAC level. Smoking status
      did not correlate with TAC. CONCLUSIONS: Total antioxidant status of lung cancer
      patients results from their disease stage and levels of endogenous antioxidants
      rather than from lifestyle factors. The lack of influence of diet and smoking on
      the TAC presumably result from disturbed homeostasis in which cancer, while
      developing, could determine the redox state to a greater extent than lifestyle
      factors.

PMID- 27688728
TI  - Evaluation of a newly discovered breast cancer susceptibility locus at 6q25.1 in
      Iranian Azari-Turkish women.
AB  - AIM OF THE STUDY: A recent breast cancer genome-wide association study (GWAS)
      identified single-nucleotide polymorphism (SNP) rs2046210 on 6q25.1 showing a
      strong association with breast cancer risk. Numerous association studies have
      been conducted to investigate the relationship between this polymorphism and
      breast cancer risk in various populations. There have been conflicting reports
      about the association of this locus with breast cancer risk in different ethnic
      groups. For the first time, this study has investigated the association of
      rs2046210 SNP with breast cancer risk in Iranian Azari-Turkish women in North
      West Iran. MATERIAL AND METHODS: In this study 192 breast cancer subjects and 186
      healthy controls were genotyped using Taqman SNP genotyping assays for different
      SNP rs2046210 alleles. RESULTS: No significant association between rs2046210 SNP
      alleles and the risk of breast cancer was detected in Iranian Azari-Turkish
      women. CONCLUSIONS: The data suggests that rs2046210SNP does not play a role in
      the aetiology of breast cancer in the Iranian Azari-Turkish population, and it
      indicates possible genetic differences for breast cancer between different
      population ancestries. Our result is an important contribution to the literature
      about genetic susceptibility for breast cancer in Asian populations. Additional
      studies are required to confirm our findings.

PMID- 27688729
TI  - Histological characterisation and prognostic evaluation of 62 gastric
      neuroendocrine carcinomas.
AB  - AIM OF THE STUDY: To determine the significance of expression of synaptophysin,
      chromogranin A, and Ki-67 and their association with clinicopathological
      parameters, and to find out the possible prognostic factors in gastric
      neuroendocrine carcinoma (G-NEC). MATERIAL AND METHODS: We investigated the
      immunohistochemical features and prognosis of 62 G-NECs, and evaluated the
      association among expressions of synaptophysin, chromogranin A, and Ki-67,
      clinicopathological variables, and outcome. RESULTS: Chromogranin A expression
      was found more commonly in small-cell NECs (9/9, 100%) than in large-cell NECs
      (27/53, 51%) (p = 0.008). No statistical significance was found in Ki-67 (p =
      0.494) or synaptophysin (p > 0.1) expression between NEC cell types. Correlation
      analyses revealed that Ki-67 expression was significantly associated with mid
      third disease of stomach (p = 0.005) and vascular involvement (p = 0.006), and
      had a trend of significant correlation with tumour relapse (p = 0.078). High
      expression of chromogranin A was significantly associated with histology of small
      cell NECs (p = 0.008) and lesser tumour greatest dimension (p = 0.038). The
      prognostic significance was determined by means of Kaplan-Meier survival
      estimates and log-rank tests, and as a result, early TNM staging and
      postoperative chemotherapy were found to be correlated with longer overall
      survival (p < 0.05). Univariate analysis revealed associations between poor
      prognosis in NECs and several factors, including high TNM staging (p = 0.048),
      vascular involvement (p = 0.023), relapse (p = 0.004), and
      microscopic/macroscopic residual tumour (R1/2, p < 0.001). In a multivariate
      analysis, relapse was identified as the sole independent prognostic factor.
      CONCLUSIONS: No significant correlation between survival and expression of
      synaptophysin, chromogranin A, or Ki-67 has been determined in G-NECs. Our study
      indicated that early diagnosis, no-residual-tumour resection, and postoperative
      chemotherapy were possible prognostic factors.

PMID- 27688730
TI  - Interferon-alpha reduces the gefitinib sensitivity of human non-small cell lung
      cancer.
AB  - AIM OF THE STUDY: Many studies have shown that interferon-alpha (IFN-alpha)
      enhances the antiproliferative effect of gefitinib in some solid tumours. We
      aimed to determine the effect of combining IFN-alpha with gefitinib in human non
      small cell lung cancer (NSCLC) cell lines (A549, H1299, HCC827) with different
      EGFR and K-Ras gene statuses. MATERIAL AND METHODS: An MTT assay was used to
      assess cell proliferation. Apoptosis was detected by an Annexin V/propidium
      iodide assay using flow cytometry, and western blotting was used to determine the
      expression of epidermal growth factor receptor/phosphorylated epidermal growth
      factor receptor (EGFR/p-EGFR) and signal transducers and activators of
      transcription 3/phosphorylated signal transducers and activators of transcription
      3 (STAT3/p-STAT3). RESULTS: There was an additive interaction when gefitinib was
      combined with IFN-alpha in all cell lines; however, there was antagonism when
      gefitinib followed IFN-alpha pretreatment in three cell lines. Notably, IFN-alpha
      pretreatment significantly reduced the gefitinib sensitivity of HCC827 cells.
      Surprisingly, while IFN-alpha inhibited STAT3 phosphorylation in cell lines,
      gefitinib could do so. CONCLUSIONS: The results might confirm the hypothesis that
      IFN-alpha induces gefitinib sensitivity of NSCLC, and IFN-alpha inhibits
      phosphorylation of STAT3, which may be dependent on EGFR signal activation
      playing a role in the reduction of gefitinib sensitivity after IFN-alpha
      treatment in NSCLC cell lines.

PMID- 27688731
TI  - Comparison of the hypothetical (57)Co brachytherapy source with the (192)Ir
      source.
AB  - AIM OF THE STUDY: The (57)Co radioisotope has recently been proposed as a
      hypothetical brachytherapy source due to its high specific activity, appropriate
      half-life (272 days) and medium energy photons (114.17 keV on average). In this
      study, Task Group No. 43 dosimetric parameters were calculated and reported for a
      hypothetical (57)Co source. MATERIAL AND METHODS: A hypothetical (57)Co source
      was simulated in MCNPX, consisting of an active cylinder with 3.5 mm length and
      0.6 mm radius encapsulated in a stainless steel capsule. Three photon energies
      were utilized (136 keV [10.68%], 122 keV [85.60%], 14 keV [9.16%]) for the (57)Co
      source. Air kerma strength, dose rate constant, radial dose function, anisotropy
      function, and isodose curves for the source were calculated and compared to the
      corresponding data for a (192)Ir source. RESULTS: The results are presented as
      tables and figures. Air kerma strength per 1 mCi activity for the (57)Co source
      was 0.46 cGyh(-1) cm 2 mCi(-1). The dose rate constant for the (57)Co source was
      determined to be 1.215 cGyh(-1)U(-1). The radial dose function for the (57)Co
      source has an increasing trend due to multiple scattering of low energy photons.
      The anisotropy function for the (57)Co source at various distances from the
      source is more isotropic than the (192)Ir source. CONCLUSIONS: The (57)Co source
      has advantages over (192)Ir due to its lower energy photons, longer half-life,
      higher dose rate constant and more isotropic anisotropic function. However, the
      (192)Ir source has a higher initial air kerma strength and more uniform radial
      dose function. These properties make (57)Co a suitable source for use in
      brachytherapy applications.

PMID- 27688732
TI  - Male breast cancer: a clinicopathological study of an Egyptian population
      (Alexandria experience).
AB  - AIM OF THE STUDY: The purpose of this retrospective study is to evaluate the
      clinicopathological features and treatment results of male breast cancer
      presented to our tertiary referral center. MATERIAL AND METHODS: Between January
      1998 and December 2005, a total of 39 men with breast cancer treated at
      Alexandria Main University Hospital and their medical records were reviewed.
      RESULTS: The median age of patients was 59 years. Only 3 (7.7%) patients had
      positive family history. All patients presented by breast swellings that were
      associated with axillary mass in about one third of them. Around 80% had hormone
      receptor positive (estrogen and/or progesterone receptors). Two third of patients
      had advanced T-stage (T3 and T4). Left sided breast cancer occurred in 51.3%.
      Infiltrating ductal carcinoma was the most common type of histology encountered
      and grade 2 was the predominant grade of tumor. Modified radical mastectomy was
      the most common (87.2%) type of surgery done followed by chemotherapy for 32
      patients and loco-regional radiotherapy for 20 patients. Tamoxifen was
      administered in 31 patients. Distant relapse occurred in 7 patients (17.9%) and
      local recurrence occurred in 2 patients (5.1%). The 5-year disease-free survival
      (DFS) was 82% and the 5-year overall survival (OS) rate was 84%. Only negative
      axillary lymph node and positive hormone receptor status were significantly
      associated with favorable DFS and OS. T-stage, grade of tumor and type of
      chemotherapy given had no statistically significant impact on either DFS or OS.
      CONCLUSIONS: Male breast cancer is still under-investigated and further
      researches are warranted.

PMID- 27688733
TI  - Patterns of care in patients with muscle-invasive bladder cancer - a
      retrospective cohort study.
AB  - A potential reason for poor survival among patients with muscle-invasive bladder
      cancer (MIBC) in Poland is initial disqualification from curative treatment due
      to advanced stage of the disease or low performance status. The aim of this study
      was to describe patterns of care in patients with newly diagnosed MIBC. This is a
      multicentre retrospective cohort study involving 296 consecutive patients with
      primary histologically diagnosed MIBC. Therapeutic decisions and potentially
      underlying clinical factors were analysed. Full clinical data was available for
      285 patients. One hundred and sixty-four (57.5%) patients were qualified for
      radical cystectomy (RC), 32 (11.2%) patients for a second step of transurethral
      resection of the bladder tumour (TURBT) intentionally followed by systemic
      chemotherapy, four (1.4%) patients after complete TURBT were qualified for
      adjuvant intravesical chemotherapy only, while the remaining 85 (29.8%) patients
      were qualified for palliative treatment in the form of chemotherapy and/or
      radiotherapy and/or best supportive care. Patients disqualified from curative
      treatment were older (78 vs. 69 years, p < 0.02), had lower BMI values (24.5 vs.
      25.7 kg/m(2), p < 0.02), lower haemoglobin concentration (11.6 vs. 12.9 mg/l, p <
      0.02), declared lower rate of nicotine abuse (50.5% vs. 72.1%, p < 0.02), and had
      a shorter time interval between first symptom and diagnosis (30 vs. 60 days, p =
      0.02). As the majority of Polish patients with primary MIBC receive curative
      treatment, the stage of the disease alone seems not to be the leading cause of
      poor survival. However, appropriateness of qualification for RC and treatment
      quality needs to be assessed for final conclusion on the factors influencing
      outcomes of treatment in Poland. 

PMID- 27688734
TI  - Oxidative profile of sickle cell patients in a Cameroonian urban hospital.
AB  - BACKGROUND: Sickle cell disease (SCD) is a class of hemoglobinopathy resulting
      from a single mutation in the beta-globin chain inducing the substitution of
      valine for glutamic acid at the sixth amino acid position which leads to the
      production of abnormal haemoglobin (haemoglobin S [HbS]). Studies demonstrated
      the implication of oxidative stress in the development of the sickle cell
      disease. METHODS: The study aim was to determine the level of oxidative stress
      markers in a group of sickle cell homozygous patients (SS) in the Yaounde Central
      Hospital above 15 years of age. Hemolysates obtained from patients were used to
      investigate some oxidative stress markers including malondialdehyde (MDA), nitric
      oxide (NO), catalase (CAT), superoxide dismutase (SOD), peroxidase, total
      antioxidant capacity (TAC) and total protein concentration. RESULTS: Eighty four
      individuals, 42 males and 42 females participated (50 % each) with an age range
      of 15 to 55 years. The levels of markers were significantly higher in the healthy
      AA group than sickle (SS) (p < 0.05), with the exception of MDA which was
      significantly high in sickle cell (SS) patients than healthy (p = 0.037). With
      respect to the gender, both healthy and SS females showed a greater Total anti
      oxidant capacity (65 MUM) compared to the males (55 MUM). CONCLUSION: The
      increase in the oxidative stress level especially MDA in sickle cell homozygous
      patients compared to healthy AA individuals confirms that oxidative stress is
      involved in the pathogenesis of the sickle cell disease.

PMID- 27688735
TI  - Altering bioelectricity on inhibition of human breast cancer cells.
AB  - BACKGROUND: Membrane depolarization is associated with breast cancer.
      Depolarization-activated voltage-gated ion channels are directly implicated in
      the initiation, proliferation, and metastasis of breast cancer. METHODS: In this
      study, the role of voltage-gated potassium and calcium ion channel modulation was
      explored in two different invasive ductal human carcinoma cell lines, MDA-MB-231
      (triple-negative) and MCF7 (estrogen-receptor-positive). RESULTS: Resting
      membrane potential is more depolarized in MCF7 and MDA-MB-231 cells compared to
      normal human mammary epithelial cells. Increasing extracellular potassium
      concentration up to 50 mM depolarized membrane potential and greatly increased
      cell growth. Tetraethylammonium (TEA), a non-specific blocker of voltage-gated
      potassium channels, stimulated growth of MCF7 cells (control group grew by 201 %,
      1 mM TEA group grew 376 %). Depolarization-induced calcium influx was
      hypothesized as a requirement for growth of human breast cancer. Removing calcium
      from culture medium stopped growth of MDA and MCF7 cells, leading to cell death
      after 1 week. Verapamil, a blocker of voltage-gated calcium channels clinically
      used in treating hypertension and coronary disease, inhibited growth of MDA cells
      at low concentration (10-20 MUM) by 73 and 92 % after 1 and 2 days, respectively.
      At high concentration (100 MUM), verapamil killed >90 % of MDA and MCF7 cells
      after 1 day. Immunoblotting experiments demonstrated that an increased expression
      of caspase-3, critical in apoptosis signaling, positively correlated with
      verapamil concentration in MDA cells. In MCF7, caspase-9 expression is increased
      in response to verapamil. CONCLUSIONS: Our results support our hypotheses that
      membrane depolarization and depolarization-induced calcium influx stimulate
      proliferation of human breast cancer cells, independently of cancer subtypes. The
      underlying mechanism of verapamil-induced cell death involves different caspases
      in MCF7 and MDA-MB-231. These data suggest that voltage-gated potassium and
      calcium channels may be putative targets for pharmaceutical remediation in human
      invasive ductal carcinomas.

PMID- 27688736
TI  - Long noncoding RNA ANRIL is activated by hypoxia-inducible factor-1alpha and
      promotes osteosarcoma cell invasion and suppresses cell apoptosis upon hypoxia.
AB  - BACKGROUND: Osteosarcoma is the most common malignancy of bone. Intratumoral
      hypoxia occurs in many solid tumors, where it is associated with the development
      of aggressive phenotype. ANRIL has been shown to be a long noncoding RNA that
      facilitates the progression of a number of malignancies. Yet, few studies have
      explored the expression pattern of ANRIL in osteosarcoma and the effect of
      hypoxia on ANRIL. METHODS: We evaluated the expression levels of ANRIL in
      osteosarcoma tissues, adjacent normal tissues and cells with quantitative real
      time polymerase chain reaction. Multiple approaches including luciferase reporter
      assay with nucleotide substitutions, chromatin immunoprecipitation assay and
      electrophoretic mobility shift assay were used to confirm the direct binding of
      HIF-1alpha to the ANRIL promoter region. SiRNA-based knockdown and other
      molecular biology techniques were employed to measure the effect of HIF-1alpha on
      the expression of ANRIL. RESULTS: We found that the expression of ANRIL was
      upregulated in 15 pairs of osteosarcoma compared with adjacent normal tissues. We
      found that hypoxia is sufficient to upregulate ANRIL expression in osteosarcoma
      cells (MNNG and U2OS). HIF-1alpha directly binds to the putative hypoxia response
      element in the upstream region of ANRIL. What's more, siRNA and small molecular
      inhibitors-mediated HIF-1alpha suppression attenuated ANRIL upregulation under
      hypoxic conditions. Upon hypoxia, ANRIL promoted cancer cell invasion and
      suppressed cell apoptosis. CONCLUSION: Taken together, these data suggest that
      HIF-1alpha may contribute to the upregulation of ANRIL in osteosarcoma under
      hypoxic conditions. ANRIL is involved in hypoxia-induced aggressive phenotype in
      osteosarcoma.

PMID- 27688737
TI  - The effect of inhalation of Citrus sinensis flowers and Mentha spicata leave
      essential oils on lung function and exercise performance: a quasi-experimental
      uncontrolled before-and-after study.
AB  - BACKGROUND: Recently, there has been an increased interest in the effects of
      essential oils on athletic performances and other physiological effects. This
      study aimed to assess the effects of Citrus sinensis flower and Mentha spicata
      leaves essential oils inhalation in two different groups of athlete male students
      on their exercise performance and lung function. METHODS: Twenty physical
      education students volunteered to participate in the study. The subjects were
      randomly assigned into two groups: Mentha spicata and Citrus sinensis (ten
      participants each). One group was nebulized by Citrus sinensis flower oil and the
      other by Mentha spicata leaves oil in a concentration of (0.02 ml/kg of body
      mass) which was mixed with 2 ml of normal saline for 5 min before a 1500 m
      running tests. Lung function tests were measured using a spirometer for each
      student pre and post nebulization giving the same running distance pre and post
      oils inhalation. RESULTS: A lung function tests showed an improvement on the lung
      status for the students after inhaling of the oils. Interestingly, there was a
      significant increase in Forced Expiratory Volume in the first second and Forced
      Vital Capacity after inhalation for the both oils. Moreover significant
      reductions in the means of the running time were observed among these two groups.
      The normal spirometry results were 50 %, while after inhalation with M. spicata
      oil the ratio were 60 %. CONCLUSION: Our findings support the effectiveness of M.
      spicata and C. sinensis essential oils on the exercise performance and
      respiratory function parameters. However, our conclusion and generalisability of
      our results should be interpreted with caution due to small sample size and lack
      of control groups, randomization or masking. We recommend further investigations
      to explain the mechanism of actions for these two essential oils on exercise
      performance and respiratory parameters. TRIAL REGISTRATION: ISRCTN10133422,
      Registered: May 3, 2016.

PMID- 27688739
TI  - Prevalence and Predictors of Video Game Addiction: A Study Based on a National
      Representative Sample of Gamers.
AB  - Video gaming has become a popular leisure activity in many parts of the world,
      and an increasing number of empirical studies examine the small minority that
      appears to develop problems as a result of excessive gaming. This study
      investigated prevalence rates and predictors of video game addiction in a sample
      of gamers, randomly selected from the National Population Registry of Norway (N =
      3389). Results showed there were 1.4 % addicted gamers, 7.3 % problem gamers, 3.9
      % engaged gamers, and 87.4 % normal gamers. Gender (being male) and age group
      (being young) were positively associated with addicted-, problem-, and engaged
      gamers. Place of birth (Africa, Asia, South- and Middle America) were positively
      associated with addicted- and problem gamers. Video game addiction was negatively
      associated with conscientiousness and positively associated with neuroticism.
      Poor psychosomatic health was positively associated with problem- and engaged
      gaming. These factors provide insight into the field of video game addiction, and
      may help to provide guidance as to how individuals that are at risk of becoming
      addicted gamers can be identified.

PMID- 27688738
TI  - Detection of IL-17 and IL-23 in Plasma Samples of Children with Autism.
AB  - Interleukin-23 (IL-23) is a survival factor for a newly described population of T
      lymphocytes, namely Th-17 cells, that secrete IL-17, tumor necrosis factor- alpha
      (TNFalpha) and IL-6. It has been shown that Th-17 cells are a pathogenic T cell
      subset involved in autoimmune and chronic inflammatory diseases. Based on the
      increasing evidence of immune dysfunction in autism, including possible
      autoimmune and inflammatory processes, we hypothesized that Th-17 cells, a T cell
      lineage that has not been previously examined in this disorder, may be altered in
      autism. To assess the potential role, if any, of Th-17 cells in autism, we
      analyzed plasma samples obtained from children ranging in age from 2-5 years with
      a diagnosis of autism and age-matched typically developing controls for the
      presence of IL-17 and IL-23 cytokines. Plasma samples from 40 children with
      autism including 20 children with a regressive form of autism, 20 with early
      onset and no regression and 20 typically developing age-matched control children
      were analyzed for IL-17 and IL-23, under the hypothesis that altered number and
      function of Th-17 cells would directly correlate with altered levels of IL-17 and
      IL-23 in the plasma. In this study, we were able to demonstrate that IL-23
      cytokine levels were significantly different in children with autism compared
      with age-matched controls, a finding primarily driven by children with early
      onset autism. In contrast, there were no statistical differences in IL-17 levels
      autism compared with age-matched typically developing controls. This is the first
      study to report altered IL-23 production in autism. The decreased plasma IL-23
      production observed in children with autism warrants further research as to its
      affect on the generation and survival of Th-17 cells, a subset important in
      neuroinflammatory conditions that may include autism.

PMID- 27688740
TI  - The Mechanisms of Mindfulness in the Treatment of Mental Illness and Addiction.
AB  - Consistent with its growing popularity amongst the general public and medical
      community, throughout recent decades there have been increasing attempts to
      understand the mechanisms that underlie therapeutic improvement in individuals
      receiving mindfulness training. The current paper draws upon findings from
      various remits of scientific enquiry and summarises key evidence-based mechanisms
      of mindfulness that have been proposed in the academic literature to date.
      Empirical findings indicate that mindfulness targets biological, psychological,
      social, and spiritual psychopathology determinants. Furthermore, the mechanistic
      pathways exploited by mindfulness are likely to vary according to factors such as
      (i) the type of mindfulness-based intervention that is administered (e.g., first-
      or second-generation mindfulness-based interventions), (ii) the specific clinical
      disorder that is being targeted, (iii) the educational, social, and spiritual
      history of the participant, and (iv) the extent to which the mindfulness
      instructor truly embodies the principles of mindful living. It is hoped that the
      mechanisms of mindfulness discussed in this paper will contribute to the
      formulation of a more complete picture that can be tested and expanded upon
      during future scientific enquiry.

PMID- 27688742
TI  - Mapping paddy rice planting area in rice-wetland coexistent areas through
      analysis of Landsat 8 OLI and MODIS images.
AB  - Accurate and up-to-date information on the spatial distribution of paddy rice
      fields is necessary for the studies of trace gas emissions, water source
      management, and food security. The phenology-based paddy rice mapping algorithm,
      which identifies the unique flooding stage of paddy rice, has been widely used.
      However, identification and mapping of paddy rice in rice-wetland coexistent
      areas is still a challenging task. In this study, we found that the
      flooding/transplanting periods of paddy rice and natural wetlands were different.
      The natural wetlands flood earlier and have a shorter duration than paddy rice in
      the Panjin Plain, a temperate region in China. We used this asynchronous flooding
      stage to extract the paddy rice planting area from the rice-wetland coexistent
      area. MODIS Land Surface Temperature (LST) data was used to derive the
      temperature-defined plant growing season. Landsat 8 OLI imagery was used to
      detect the flooding signal and then paddy rice was extracted using the difference
      in flooding stages between paddy rice and natural wetlands. The resultant paddy
      rice map was evaluated with in-situ ground-truth data and Google Earth images.
      The estimated overall accuracy and Kappa coefficient were 95% and 0.90,
      respectively. The spatial pattern of OLI-derived paddy rice map agrees well with
      the paddy rice layer from the National Land Cover Dataset from 2010 (NLCD-2010).
      The differences between RiceLandsat and RiceNLCD are in the range of +/-20% for
      most 1-km grid cell. The results of this study demonstrate the potential of the
      phenology-based paddy rice mapping algorithm, via integrating MODIS and Landsat 8
      OLI images, to map paddy rice fields in complex landscapes of paddy rice and
      natural wetland in the temperate region.

PMID- 27688741
TI  - Increased sialylation of site specific O-glycoforms of hemopexin in liver
      disease.
AB  - BACKGROUND: Non-invasive monitoring of liver disease remains an important health
      issue. Liver secreted glycoproteins reflect pathophysiological states of the
      organ and represent a rational target for serologic monitoring. In this study, we
      describe sialylated O-glycoforms of liver-secreted hemopexin (HPX) and quantify
      them as a ratio of disialylated to monosialylated form (S-HPX). METHODS: We
      measured S-HPX in serum of participants of the HALT-C trial using a LC-MS/MS-MRM
      assay. RESULTS: Repeated measurements of S-HPX in the samples of 23 disease-free
      controls, collected at four different time points, show that the ratio remains
      stable in the healthy controls but increases with the progression of liver
      disease. The results of measurement of S-HPX in serum of participants of the HALT
      C trial show that it increased significantly (Kruskal-Wallis test, p < 0.01) in
      liver disease as the stage of fibrosis progressed in liver biopsies. We observed
      a 1.7-fold increase in fibrosis defined as Ishak score 3-4 (24.9 + 14.2, n = 22)
      and 4.7-fold increase in cirrhosis defined as Ishak score 5-6 (68.6 + 38.5; n =
      24) compared to disease-free controls (14.7 + 6.7, n = 23). S-HPX is correlated
      with AFP, bilirubin, INR, ALT, and AST while inversely correlated with platelet
      count and albumin. In an independent verification set of samples, S-HPX separated
      the Ishak 5-6 (n = 15) from the Ishak 3-4 (n = 15) participants with AuROC 0.84;
      at the same time, the Ishak 3-4 group was separated from disease-free controls (n
      = 15) with AuROC 0.82. CONCLUSION: S-HPX, a measure of sialylated O-glycoforms of
      hemopexin, progressively increases in fibrotic and cirrhotic patient of HCV
      etiology and can be quantified by an LC-MS/MS-MRM assay in unfractionated serum
      of patients. Quantification of sialylated O-glycoforms of this liver secreted
      glycoprotein represents a novel measure of the stage of liver disease that could
      have a role in monitoring the progression of liver pathology.

PMID- 27688744
TI  - Detecting Visually Observable Disease Symptoms from Faces.
AB  - Recent years have witnessed an increasing interest in the application of machine
      learning to clinical informatics and healthcare systems. A significant amount of
      research has been done on healthcare systems based on supervised learning. In
      this study, we present a generalized solution to detect visually observable
      symptoms on faces using semi-supervised anomaly detection combined with machine
      vision algorithms. We rely on the disease-related statistical facts to detect
      abnormalities and classify them into multiple categories to narrow down the
      possible medical reasons of detecting. Our method is in contrast with most
      existing approaches, which are limited by the availability of labeled training
      data required for supervised learning, and therefore offers the major advantage
      of flagging any unusual and visually observable symptoms.

PMID- 27688745
TI  - Retinal Fundus Image Enhancement Using the Normalized Convolution and Noise
      Removing.
AB  - Retinal fundus image plays an important role in the diagnosis of retinal related
      diseases. The detailed information of the retinal fundus image such as small
      vessels, microaneurysms, and exudates may be in low contrast, and retinal image
      enhancement usually gives help to analyze diseases related to retinal fundus
      image. Current image enhancement methods may lead to artificial boundaries,
      abrupt changes in color levels, and the loss of image detail. In order to avoid
      these side effects, a new retinal fundus image enhancement method is proposed.
      First, the original retinal fundus image was processed by the normalized
      convolution algorithm with a domain transform to obtain an image with the basic
      information of the background. Then, the image with the basic information of the
      background was fused with the original retinal fundus image to obtain an enhanced
      fundus image. Lastly, the fused image was denoised by a two-stage denoising
      method including the fourth order PDEs and the relaxed median filter. The retinal
      image databases, including the DRIVE database, the STARE database, and the
      DIARETDB1 database, were used to evaluate image enhancement effects. The results
      show that the method can enhance the retinal fundus image prominently. And,
      different from some other fundus image enhancement methods, the proposed method
      can directly enhance color images. 

PMID- 27688743
TI  - An Automated Approach for Localizing Retinal Blood Vessels in Confocal Scanning
      Laser Ophthalmoscopy Fundus Images.
AB  - In this work, we present a rules-based method for localizing retinal blood
      vessels in confocal scanning laser ophthalmoscopy (cSLO) images and evaluate its
      feasibility. A total of 31 healthy participants (17 female; mean age: 64.0 +/-
      8.2 years) were studied using manual and automatic segmentation. High-resolution
      peripapillary scan acquisition cSLO images were acquired. The automated
      segmentation method consisted of image pre-processing for gray-level
      homogenization and blood vessel enhancement (morphological opening operation,
      Gaussian filter, morphological Top-Hat transformation), binary thresholding
      (entropy-based thresholding operation), and removal of falsely detected isolated
      vessel pixels. The proposed algorithm was first tested on the publically
      available dataset DRIVE, which contains color fundus photographs, and compared to
      performance results from the literature. Good results were obtained.
      Monochromatic cSLO images segmented using the proposed method were compared to
      those manually segmented by two independent observers. For the algorithm, a
      sensitivity of 0.7542, specificity of 0.8607, and accuracy of 0.8508 were
      obtained. For the two independent observers, a sensitivity of 0.6579, specificity
      of 0.9699, and accuracy of 0.9401 were obtained. The results demonstrate that it
      is possible to localize vessels in monochromatic cSLO images of the retina using
      a rules-based approach. The performance results are inferior to those obtained
      using fundus photography, which could be due to the nature of the technology.

PMID- 27688747
TI  - High-Resolution Cortical Dipole Imaging Using Spatial Inverse Filter Based on
      Filtering Property.
AB  - Cortical dipole imaging has been developed to visualize brain electrical activity
      in high spatial resolution. It is necessary to solve an inverse problem to
      estimate the cortical dipole distribution from the scalp potentials. In the
      present study, the accuracy of cortical dipole imaging was improved by focusing
      on filtering property of the spatial inverse filter. We proposed an inverse
      filter that optimizes filtering property using a sigmoid function. The ability of
      the proposed method was compared with the traditional inverse techniques, such as
      Tikhonov regularization, truncated singular value decomposition (TSVD), and
      truncated total least squares (TTLS), in a computer simulation. The proposed
      method was applied to human experimental data of visual evoked potentials. As a
      result, the estimation accuracy was improved and the localized dipole
      distribution was obtained with less noise.

PMID- 27688746
TI  - Discovering Patterns in Brain Signals Using Decision Trees.
AB  - Even with emerging technologies, such as Brain-Computer Interfaces (BCI) systems,
      understanding how our brains work is a very difficult challenge. So we propose to
      use a data mining technique to help us in this task. As a case of study, we
      analyzed the brain's behaviour of blind people and sighted people in a spatial
      activity. There is a common belief that blind people compensate their lack of
      vision using the other senses. If an object is given to sighted people and we
      asked them to identify this object, probably the sense of vision will be the most
      determinant one. If the same experiment was repeated with blind people, they will
      have to use other senses to identify the object. In this work, we propose a
      methodology that uses decision trees (DT) to investigate the difference of how
      the brains of blind people and people with vision react against a spatial
      problem. We choose the DT algorithm because it can discover patterns in the brain
      signal, and its presentation is human interpretable. Our results show that using
      DT to analyze brain signals can help us to understand the brain's behaviour.

PMID- 27688748
TI  - Fuzzy Logic Based Control for Autonomous Mobile Robot Navigation.
AB  - This paper describes the design and the implementation of a trajectory tracking
      controller using fuzzy logic for mobile robot to navigate in indoor environments.
      Most of the previous works used two independent controllers for navigation and
      avoiding obstacles. The main contribution of the paper can be summarized in the
      fact that we use only one fuzzy controller for navigation and obstacle avoidance.
      The used mobile robot is equipped with DC motor, nine infrared range (IR) sensors
      to measure the distance to obstacles, and two optical encoders to provide the
      actual position and speeds. To evaluate the performances of the intelligent
      navigation algorithms, different trajectories are used and simulated using MATLAB
      software and SIMIAM navigation platform. Simulation results show the performances
      of the intelligent navigation algorithms in terms of simulation times and
      travelled path.

PMID- 27688749
TI  - Reduced Representation Bisulfite Sequencing Determination of Distinctive DNA
      Hypermethylated Genes in the Progression to Colon Cancer in African Americans.
AB  - Background and Aims. Many studies have focused on the determination of methylated
      targets in colorectal cancer. However, few analyzed the progressive methylation
      in the sequence from normal to adenoma and ultimately to malignant tumors. This
      is of utmost importance especially in populations such as African Americans who
      generally display aggressive tumors at diagnosis and for whom markers of early
      neoplasia are needed. We aimed to determine methylated targets in the path to
      colon cancer in African American patients using Reduced Representation Bisulfite
      Sequencing (RRBS). Methods. Genomic DNA was isolated from fresh frozen tissues of
      patients with different colon lesions: normal, a tubular adenoma, a tubulovillous
      adenoma, and five cancers. RRBS was performed on these DNA samples to identify
      hypermethylation. Alignment, mapping, and confirmed CpG methylation analyses were
      performed. Preferential hypermethylated pathways were determined using Ingenuity
      Pathway Analysis (IPA). Results. We identified hypermethylated CpG sites in the
      following genes: L3MBTL1, NKX6-2, PREX1, TRAF7, PRDM14, and NEFM with the number
      of CpG sites being 14, 17, 10, 16, 6, and 6, respectively, after pairwise
      analysis of normal versus adenoma, adenoma versus cancer, and normal versus
      cancer. IPA mapped the above-mentioned hypermethylated genes to the Wnt/beta
      catenin, PI3k/AKT, VEGF, and JAK/STAT3 signaling pathways. Conclusion. This work
      provides insight into novel differential CpGs hypermethylation sites in
      colorectal carcinogenesis. Functional analysis of the novel gene targets is
      needed to confirm their roles in their associated carcinogenic pathways. 

PMID- 27688751
TI  - Novel Bioceramic Urethral Bulking Agents Elicit Improved Host Tissue Responses in
      a Rat Model.
AB  - Objectives. To test the physical properties and host response to the bioceramic
      particles, silica-calcium phosphate (SCPC10) and Cristobalite, in a rat animal
      model and compare their biocompatibility to the current clinically utilized
      urethral bulking materials. Material and Methods. The novel bulking materials,
      SCPC10 and Cristobalite, were suspended in hyaluronic acid sodium salt and
      injected into the mid urethra of a rat. Additional animals were injected with
      bulking materials currently in clinical use. Physiological response was assessed
      using voiding trials, and host tissue response was evaluated using hard tissue
      histology and immunohistochemical analysis. Distant organs were evaluated for the
      presence of particles or their components. Results. Histological analysis of the
      urethral tissue five months after injection showed that both SCPC10 and
      Cristobalite induced a more robust fibroblastic and histiocytic reaction,
      promoting integration and encapsulation of the particle aggregates, leading to a
      larger bulking effect. Concentrations of Ca, Na, Si, and P ions in the
      experimental groups were comparable to control animals. Conclusions. This side-by
      side examination of urethral bulking agents using a rat animal model and hard
      tissue histology techniques compared two newly developed bioactive ceramic
      particles to three of the currently used bulking agents. The local host tissue
      response and bulking effects of bioceramic particles were superior while also
      possessing a comparable safety profile. 

PMID- 27688752
TI  - The Self-Perception and Usage of Medical Apps amongst Medical Students in the
      United States: A Cross-Sectional Survey.
AB  - Background. Mobile medical software applications (apps) are used for clinical
      decision-making at the point of care. Objectives. To determine (1) the usage,
      reliability, and popularity of mobile medical apps and (2) medical students'
      perceptions of app usage effect on the quality of patient-provider interaction in
      healthcare settings. Methods. An anonymous web-based survey was distributed to
      medical students. Frequency of use, type of app used, and perceptions of
      reliability were assessed via univariate analysis. Results. Seven hundred thirty
      one medical students responded, equating to a response rate of 29%. The majority
      (90%) of participants thought that medical apps enhance clinical knowledge, and
      61% said that medical apps are as reliable as textbooks. While students thought
      that medical apps save time, improve the care of their patients, and improve
      diagnostic accuracy, 53% of participants believed that mobile device use in front
      of colleagues and patients makes one appear less competent. Conclusion. While
      medical students believe in the utility and reliability of medical apps, they
      were hesitant to use them out of fear of appearing less engaged. Higher levels of
      training correlated with a greater degree of comfort when using medical apps in
      front of patients. 

PMID- 27688750
TI  - Nutrition and Helicobacter pylori: Host Diet and Nutritional Immunity Influence
      Bacterial Virulence and Disease Outcome.
AB  - Helicobacter pylori colonizes the stomachs of greater than 50% of the world's
      human population making it arguably one of the most successful bacterial
      pathogens. Chronic H. pylori colonization results in gastritis in nearly all
      patients; however in a subset of people, persistent infection with H. pylori is
      associated with an increased risk for more severe disease outcomes including B
      cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma) and invasive
      adenocarcinoma. Research aimed at elucidating determinants that mediate disease
      progression has revealed genetic differences in both humans and H. pylori which
      increase the risk for developing gastric cancer. Furthermore, host diet and
      nutrition status have been shown to influence H. pylori-associated disease
      outcomes. In this review we will discuss how H. pylori is able to create a
      replicative niche within the hostile host environment by subverting and modifying
      the host-generated immune response as well as successfully competing for limited
      nutrients such as transition metals by deploying an arsenal of metal acquisition
      proteins and virulence factors. Lastly, we will discuss how micronutrient
      availability or alterations in the gastric microbiome may exacerbate negative
      disease outcomes associated with H. pylori colonization. 

PMID- 27688753
TI  - Systematic Bioinformatic Approach for Prediction of Linear B-Cell Epitopes on
      Dengue E and prM Protein.
AB  - B-cell epitopes on the envelope (E) and premembrane (prM) proteins of dengue
      virus (DENV) were predicted using bioinformatics tools, BepiPred, Ellipro, and
      SVMTriP. Predicted epitopes, 32 and 17 for E and prM proteins, respectively, were
      then characterized for their level of conservations. The epitopes, EP4/E (48-55),
      epitope number 4 of E protein at amino acids 48-55, EP9/E (165-182), EP11/E (218
      233), EP20/E (322-349), EP21/E (326-353), EP23/E (356-365), and EP25/E (380-386),
      showed a high intraserotype conservancy with very low pan-serotype conservancy,
      demonstrating a potential target as serotype specific diagnostic markers. EP3 (30
      41) located in domain-I and EP26/E (393-409), EP27/E (416-435), EP28/E (417-430)
      located in the stem region of E protein, and EP8/prM (93-112) from the prM
      protein have a pan-serotype conservancy higher than 70%. These epitopes indicate
      a potential use as universal vaccine candidates, subjected to verification of
      their potential in viral neutralization. EP2/E (16-21), EP5/E (62-123), EP6/E (63
      89), EP19/E (310-329), and EP24/E (371-402), which have more than 50% pan
      serotype conservancies, were found on E protein regions that are important in
      host cell attachment. Previous studies further show evidence for some of these
      epitopes to generate cross-reactive neutralizing antibodies, indicating their
      importance in antiviral strategies for DENV. This study suggests that
      bioinformatic approaches are attractive first line of screening for
      identification of linear B-cell epitopes. 

PMID- 27688754
TI  - Inositols in the Treatment of Insulin-Mediated Diseases.
AB  - A growing body of research is currently focused on the role of inositol isomers
      and in particular myo-inositol (MYO-INS) and D-chiroinositol (DCI) in the
      treatment of insulin resistance states. Both isomers have been shown to exert
      insulin-mimetic action and to lower postprandial glucose. Further, insulin
      resistance-related diseases were associated to derangements in inositol
      metabolism. Thus, the aim of this review is to provide current evidence on the
      potential benefits of inositol isomers (MYO-INS and DCI) in the treatment of
      disease associated to insulin resistance such as polycystic ovary syndrome
      (PCOS), gestational diabetes, and metabolic syndrome. Finally, molecular insights
      into inositol insulin-sensitizing effects will be covered focusing on the
      possible role of inositol glycans as insulin second messengers. 

PMID- 27688755
TI  - Mammalian Period represses and de-represses transcription by displacing CLOCK
      BMAL1 from promoters in a Cryptochrome-dependent manner.
AB  - The mammalian circadian clock is based on a transcription-translation feedback
      loop (TTFL) consolidated by secondary loops. In the primary TTFL, the circadian
      locomotor output cycles kaput (CLOCK)-brain and muscle Arnt-like protein-1
      (BMAL1) heterodimer acts as the transcriptional activator, and Cryptochrome (CRY)
      and Period (PER) proteins function as repressors. PER represses by displacing
      CLOCK-BMAL1 from promoters in a CRY-dependent manner. Interestingly, genes with
      complex promoters may either be repressed or de-repressed by PER, depending on
      the particular promoter regulatory elements. Here, using mouse cell lines with
      defined knockout mutations in clock genes, RNA-seq, ChIP-seq, and reporter gene
      assays coupled with measurements of DNA-protein interactions in nuclear extracts,
      we elucidate the dual functions of PER as repressor and de-repressor in a context
      dependent manner.

PMID- 27688756
TI  - Blue protein with red fluorescence.
AB  - The walleye (Sander vitreus) is a golden yellow fish that inhabits the Northern
      American lakes. The recent sightings of the blue walleye and the correlation of
      its sighting to possible increased UV radiation have been proposed earlier. The
      underlying molecular basis of its adaptation to increased UV radiation is the
      presence of a protein (Sandercyanin)-ligand complex in the mucus of walleyes.
      Degradation of heme by UV radiation results in the formation of Biliverdin
      IXalpha (BLA), the chromophore bound to Sandercyanin. We show that Sandercyanin
      is a monomeric protein that forms stable homotetramers on addition of BLA to the
      protein. A structure of the Sandercyanin-BLA complex, purified from the fish
      mucus, reveals a glycosylated protein with a lipocalin fold. This protein-ligand
      complex absorbs light in the UV region (lambdamax of 375 nm) and upon excitation
      at this wavelength emits in the red region (lambdamax of 675 nm). Unlike all
      other known biliverdin-bound fluorescent proteins, the chromophore is
      noncovalently bound to the protein. We provide here a molecular rationale for the
      observed spectral properties of Sandercyanin.

PMID- 27688757
TI  - Cisplatin DNA damage and repair maps of the human genome at single-nucleotide
      resolution.
AB  - Cisplatin is a major anticancer drug that kills cancer cells by damaging their
      DNA. Cancer cells cope with the drug by removal of the damages with nucleotide
      excision repair. We have developed methods to measure cisplatin adduct formation
      and its repair at single-nucleotide resolution. "Damage-seq" relies on the
      replication-blocking properties of the bulky base lesions to precisely map their
      location. "XR-seq" independently maps the removal of these damages by capturing
      and sequencing the excised oligomer released during repair. The damage and repair
      maps we generated reveal that damage distribution is essentially uniform and is
      dictated mostly by the underlying sequence. In contrast, cisplatin repair is
      heterogeneous in the genome and is affected by multiple factors including
      transcription and chromatin states. Thus, the overall effect of damages in the
      genome is primarily driven not by damage formation but by the repair efficiency.
      The combination of the Damage-seq and XR-seq methods has the potential for
      developing novel cancer therapeutic strategies.

PMID- 27688758
TI  - Transferable model for chromosome architecture.
AB  - In vivo, the human genome folds into a characteristic ensemble of 3D structures.
      The mechanism driving the folding process remains unknown. We report a
      theoretical model for chromatin (Minimal Chromatin Model) that explains the
      folding of interphase chromosomes and generates chromosome conformations
      consistent with experimental data. The energy landscape of the model was derived
      by using the maximum entropy principle and relies on two experimentally derived
      inputs: a classification of loci into chromatin types and a catalog of the
      positions of chromatin loops. First, we trained our energy function using the Hi
      C contact map of chromosome 10 from human GM12878 lymphoblastoid cells. Then, we
      used the model to perform molecular dynamics simulations producing an ensemble of
      3D structures for all GM12878 autosomes. Finally, we used these 3D structures to
      generate contact maps. We found that simulated contact maps closely agree with
      experimental results for all GM12878 autosomes. The ensemble of structures
      resulting from these simulations exhibited unknotted chromosomes, phase
      separation of chromatin types, and a tendency for open chromatin to lie at the
      periphery of chromosome territories.

PMID- 27688760
TI  - Antimicrobial lipopeptide tridecaptin A1 selectively binds to Gram-negative lipid
      II.
AB  - Tridecaptin A1 (TriA1) is a nonribosomal lipopeptide with selective antimicrobial
      activity against Gram-negative bacteria. Here we show that TriA1 exerts its
      bactericidal effect by binding to the bacterial cell-wall precursor lipid II on
      the inner membrane, disrupting the proton motive force. Biochemical and
      biophysical assays show that binding to the Gram-negative variant of lipid II is
      required for membrane disruption and that only the proton gradient is dispersed.
      The NMR solution structure of TriA1 in dodecylphosphocholine micelles with lipid
      II has been determined, and molecular modeling was used to provide a structural
      model of the TriA1-lipid II complex. These results suggest that TriA1 kills Gram
      negative bacteria by a mechanism of action using a lipid-II-binding motif.

PMID- 27688759
TI  - Oligodendrocytes contribute to motor neuron death in ALS via SOD1-dependent
      mechanism.
AB  - Oligodendrocytes have recently been implicated in the pathophysiology of
      amyotrophic lateral sclerosis (ALS). Here we show that, in vitro, mutant
      superoxide dismutase 1 (SOD1) mouse oligodendrocytes induce WT motor neuron (MN)
      hyperexcitability and death. Moreover, we efficiently derived human
      oligodendrocytes from a large number of controls and patients with sporadic and
      familial ALS, using two different reprogramming methods. All ALS oligodendrocyte
      lines induced MN death through conditioned medium (CM) and in coculture. CM
      mediated MN death was associated with decreased lactate production and release,
      whereas toxicity in coculture was lactate-independent, demonstrating that MN
      survival is mediated not only by soluble factors. Remarkably, human SOD1 shRNA
      treatment resulted in MN rescue in both mouse and human cultures when knockdown
      was achieved in progenitor cells, whereas it was ineffective in differentiated
      oligodendrocytes. In fact, early SOD1 knockdown rescued lactate impairment and
      cell toxicity in all lines tested, with the exclusion of samples carrying
      chromosome 9 ORF 72 (C9orf72) repeat expansions. These did not respond to SOD1
      knockdown nor did they show lactate release impairment. Our data indicate that
      SOD1 is directly or indirectly involved in ALS oligodendrocyte pathology and
      suggest that in this cell type, some damage might be irreversible. In addition,
      we demonstrate that patients with C9ORF72 represent an independent patient group
      that might not respond to the same treatment.

PMID- 27688761
TI  - Transparent antifouling material for improved operative field visibility in
      endoscopy.
AB  - Camera-guided instruments, such as endoscopes, have become an essential component
      of contemporary medicine. The 15-20 million endoscopies performed every year in
      the United States alone demonstrate the tremendous impact of this technology.
      However, doctors heavily rely on the visual feedback provided by the endoscope
      camera, which is routinely compromised when body fluids and fogging occlude the
      lens, requiring lengthy cleaning procedures that include irrigation, tissue
      rubbing, suction, and even temporary removal of the endoscope for external
      cleaning. Bronchoscopies are especially affected because they are performed on
      delicate tissue, in high-humidity environments with exposure to extremely
      adhesive biological fluids such as mucus and blood. Here, we present a repellent,
      liquid-infused coating on an endoscope lens capable of preventing vision loss
      after repeated submersions in blood and mucus. The material properties of the
      coating, including conformability, mechanical adhesion, transparency, oil type,
      and biocompatibility, were optimized in comprehensive in vitro and ex vivo
      studies. Extensive bronchoscopy procedures performed in vivo on porcine lungs
      showed significantly reduced fouling, resulting in either unnecessary or ~10-15
      times shorter and less intensive lens clearing procedures compared with an
      untreated endoscope. We believe that the material developed in this study opens
      up opportunities in the design of next-generation endoscopes that will improve
      visual field, display unprecedented antibacterial and antifouling properties,
      reduce the duration of the procedure, and enable visualization of currently
      unreachable parts of the body, thus offering enormous potential for disease
      diagnosis and treatment.

PMID- 27688763
TI  - An advanced modeling study on the impacts and atmospheric implications of
      multiphase dimethyl sulfide chemistry.
AB  - Oceans dominate emissions of dimethyl sulfide (DMS), the major natural sulfur
      source. DMS is important for the formation of non-sea salt sulfate (nss-SO42-)
      aerosols and secondary particulate matter over oceans and thus, significantly
      influence global climate. The mechanism of DMS oxidation has accordingly been
      investigated in several different model studies in the past. However, these
      studies had restricted oxidation mechanisms that mostly underrepresented
      important aqueous-phase chemical processes. These neglected but highly effective
      processes strongly impact direct product yields of DMS oxidation, thereby
      affecting the climatic influence of aerosols. To address these shortfalls, an
      extensive multiphase DMS chemistry mechanism, the Chemical Aqueous Phase Radical
      Mechanism DMS Module 1.0, was developed and used in detailed model investigations
      of multiphase DMS chemistry in the marine boundary layer. The performed model
      studies confirmed the importance of aqueous-phase chemistry for the fate of DMS
      and its oxidation products. Aqueous-phase processes significantly reduce the
      yield of sulfur dioxide and increase that of methyl sulfonic acid (MSA), which is
      needed to close the gap between modeled and measured MSA concentrations. Finally,
      the simulations imply that multiphase DMS oxidation produces equal amounts of MSA
      and sulfate, a result that has significant implications for nss-SO42- aerosol
      formation, cloud condensation nuclei concentration, and cloud albedo over oceans.
      Our findings show the deficiencies of parameterizations currently used in higher
      scale models, which only treat gas-phase chemistry. Overall, this study shows
      that treatment of DMS chemistry in both gas and aqueous phases is essential to
      improve the accuracy of model predictions.

PMID- 27688762
TI  - Noninvasive chromosome screening of human embryos by genome sequencing of embryo
      culture medium for in vitro fertilization.
AB  - Preimplantation genetic screening (PGS) is widely used to select in vitro
      fertilized embryos free of chromosomal abnormalities and to improve the clinical
      outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it
      requires biopsy of the preimplantation human embryo, which can limit the clinical
      applicability of PGS due to the invasiveness and complexity of the process. Here,
      we present and validate a noninvasive chromosome screening (NICS) method based on
      sequencing the genomic DNA secreted into the culture medium from the human
      blastocyst. By using multiple annealing and looping-based amplification cycles
      (MALBAC) for whole-genome amplification (WGA), we performed next-generation
      sequencing (NGS) on the spent culture medium used to culture human blastocysts (n
      = 42) and obtained the ploidy information of all 24 chromosomes. We validated
      these results by comparing each with their corresponding whole donated embryo and
      obtained a high correlation for identification of chromosomal abnormalities
      (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we
      performed chromosome screening on IVF embryos from seven couples with balanced
      translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved
      successful clinical pregnancies, and five have already achieved healthy live
      births thus far. The NICS method avoids the need for embryo biopsy and therefore
      substantially increases the safety of its use. The method has the potential of
      much wider chromosome screening applicability in clinical IVF, due to its high
      accuracy and noninvasiveness.

PMID- 27688764
TI  - Rawlsian maximin rule operates as a common cognitive anchor in distributive
      justice and risky decisions.
AB  - Distributive justice concerns the moral principles by which we seek to allocate
      resources fairly among diverse members of a society. Although the concept of fair
      allocation is one of the fundamental building blocks for societies, there is no
      clear consensus on how to achieve "socially just" allocations. Here, we examine
      neurocognitive commonalities of distributive judgments and risky decisions. We
      explore the hypothesis that people's allocation decisions for others are closely
      related to economic decisions for oneself at behavioral, cognitive, and neural
      levels, via a concern about the minimum, worst-off position. In a series of
      experiments using attention-monitoring and brain-imaging techniques, we
      investigated this "maximin" concern (maximizing the minimum possible payoff) via
      responses in two seemingly disparate tasks: third-party distribution of rewards
      for others, and choosing gambles for self. The experiments revealed three robust
      results: (i) participants' distributive choices closely matched their risk
      preferences-"Rawlsians," who maximized the worst-off position in distributions
      for others, avoided riskier gambles for themselves, whereas "utilitarians," who
      favored the largest-total distributions, preferred riskier but more profitable
      gambles; (ii) across such individual choice preferences, however, participants
      generally showed the greatest spontaneous attention to information about the
      worst possible outcomes in both tasks; and (iii) this robust concern about the
      minimum outcomes was correlated with activation of the right temporoparietal
      junction (RTPJ), the region associated with perspective taking. The results
      provide convergent evidence that social distribution for others is
      psychologically linked to risky decision making for self, drawing on common
      cognitive-neural processes with spontaneous perspective taking of the worst-off
      position.

PMID- 27688765
TI  - Surfactant adsorption kinetics in microfluidics.
AB  - Emulsions are metastable dispersions. Their lifetimes are directly related to the
      dynamics of surfactants. We design a microfluidic method to measure the kinetics
      of adsorption of surfactants to the droplet interface, a key process involved in
      foaming, emulsification, and droplet coarsening. The method is based on the pH
      decay in the droplet as a direct measurement of the adsorption of a carboxylic
      acid surfactant to the interface. From the kinetic measurement of the bulk
      equilibration of the pH, we fully determine the adsorption process of the
      surfactant. The small droplet size and the convection during the droplet flow
      ensure that the transport of surfactant through the bulk is not limiting the
      kinetics of adsorption. To validate our measurements, we show that the adsorption
      process determines the timescale required to stabilize droplets against
      coalescence, and we show that the interface should be covered at more than
      [Formula: see text] to prevent coalescence. We therefore quantitatively link the
      process of adsorption/desorption, the stabilization of emulsions, and the
      kinetics of solute partitioning-here through ion exchange-unraveling the
      timescales governing these processes. Our method can be further generalized to
      other surfactants, including nonionic surfactants, by making use of fluorophore
      surfactant interactions.

PMID- 27688766
TI  - Catalysis at the nanoscale may change selectivity.
AB  - Among the many virtues ascribed to catalytic nanoparticles, the prospect that the
      passage from the macro- to the nanoscale may change product selectivity attracts
      increasing attention. To date, why such effects may exist lacks explanation.
      Guided by recent experimental reports, we propose that the effects may result
      from the coupling between the chemical steps in which the reactant,
      intermediates, and products are involved and transport of these species toward
      the catalytic surface. Considering as a thought experiment the competitive
      formation of hydrogen and formate upon reduction of hydrogenocarbonate ions on
      metals like palladium or platinum, a model is developed that allows one to
      identify the governing parameters and predict the effect of nanoscaling on
      selectivity. The model leads to a master equation relating product selectivity
      and thickness of the diffusion layer. The latter parameter varies considerably
      upon passing from the macro- to the nanoscale, thus predicting considerable
      variations of product selectivity. These are subtle effects in the sense that the
      same mechanism might exhibit a reverse variation of the selectivity if the set of
      parameter values were different. An expression is given that allows one to
      predict the direction of the effect. There has been a tendency to assign the
      catalytic effects of nanoscaling to chemical reactivity changes of the active
      surface. Such factors might be important in some circumstances. We, however,
      insist on the likely role of short-distance transport on product selectivity,
      which could have been thought, at first sight, as the exclusive domain of
      chemical factors.

PMID- 27688767
TI  - Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP
      peptide ex vivo.
AB  - Bladder cancer is the fifth most common in incidence and one of the most
      expensive cancers to treat. Early detection greatly improves the chances of
      survival and bladder preservation. The pH low insertion peptide (pHLIP)
      conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets
      low extracellular pH, allowing visualization of malignant lesions in human
      bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery
      were immediately irrigated with nonbuffered saline and instilled with a solution
      of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently
      opened and imaged, the fluorescent spots were marked, and a standard pathological
      analysis was carried out to establish the correlation between ICG pHLIP imaging
      and white light pathological assessment. Accurate targeting of bladder lesions
      was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80%
      if targeting of necrotic tissue from previous transurethral resections or
      chemotherapy are considered as false positives. The ICG pHLIP imaging agent
      marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle
      invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only
      four cases were seen using white light, so imaging with the ICG pHLIP peptide
      offers improved early diagnosis of bladder cancers and may also enable new
      treatment alternatives.

PMID- 27688769
TI  - Immunogenicity of RSV F DNA Vaccine in BALB/c Mice.
AB  - Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract
      disease leading to numerous hospitalizations and deaths among the infant and
      elderly populations worldwide. There is no vaccine or a less effective drug
      available against RSV infections. Natural RSV infection stimulates the Th1 immune
      response and activates the production of neutralizing antibodies, while earlier
      vaccine trials that used UV-inactivated RSV exacerbated the disease due to the
      activation of the allergic Th2 response. With a focus on Th1 immunity, we
      developed a DNA vaccine containing the native RSV fusion (RSV F) protein and
      studied its immune response in BALB/c mice. High levels of RSV specific
      antibodies were induced during subsequent immunizations. The serum antibodies
      were able to neutralize RSV in vitro. The RSV inhibition by sera was also shown
      by immunofluorescence analyses. Antibody response of the RSV F DNA vaccine showed
      a strong Th1 response. Also, sera from RSV F immunized and RSV infected mice
      reduced the RSV infection by 50% and 80%, respectively. Our data evidently showed
      that the RSV F DNA vaccine activated the Th1 biased immune response and led to
      the production of neutralizing antibodies, which is the desired immune response
      required for protection from RSV infections. 

PMID- 27688771
TI  - Phosphate Solubilization Potential of Rhizosphere Fungi Isolated from Plants in
      Jimma Zone, Southwest Ethiopia.
AB  - Phosphorus (P) is one of the major bioelements limiting agricultural production.
      Phosphate solubilizing fungi play a noteworthy role in increasing the
      bioavailability of soil phosphates for plants. The present study was aimed at
      isolating and characterizing phosphate solubilizing fungi from different
      rhizospheres using both solid and liquid Pikovskaya (PVK) medium. A total of 359
      fungal isolates were obtained from 150 rhizosphere soil samples of haricot bean,
      faba bean, cabbage, tomato, and sugarcane. Among the isolates, 167 (46.52%)
      solubilized inorganic phosphate. The isolated phosphate solubilizing fungi
      belonged to genera of Aspergillus (55.69%), Penicillium spp. (23.35%), and
      Fusarium (9.58%). Solubilization index (SI) ranged from 1.10 to 3.05. Isolates
      designated as JUHbF95 (Aspergillus sp.) and JUFbF59 (Penicillium sp.) solubilized
      maximum amount of P 728.77 MUg.mL(-1) and 514.44 MUg mL(-1), respectively, from
      TCP (tricalcium phosphate) after 15 days of incubation. The highest (363 MUg mL(
      1)) soluble-P was released from RP with the inoculation of JUHbF95 in the PVK
      broth after 10 days of incubation. The present study indicated the presence of
      diverse plant associated P-solubilizing fungi that may serve as potential
      biofertilizers. 

PMID- 27688768
TI  - Dysregulation of Notch and ERalpha signaling in AhR-/- male mice.
AB  - The aryl hydrocarbon receptor (AhR) is now recognized as an important
      physiological regulator in the immune and reproductive systems, and in the
      development of the liver and vascular system. AhR regulates cell cycle, cell
      proliferation, and differentiation through interacting with other signaling
      pathways, like estrogen receptor alpha (ERalpha), androgen receptor (AR), and
      Notch signaling. In the present study, we investigated Notch and estrogen
      signaling in AhR-/- mice. We found low fertility with degenerative changes in the
      testes, germ cell apoptosis, and a reduced number of early spermatids. There was
      no change in aromatase, AR, ERalpha, or ERbeta expression in the testis and no
      detectable change in serum estrogen levels. However, expression of Notch
      receptors (Notch1 and Notch3) and their target Hairy and Enhancer of Split
      homolog 1 (HES1) was reduced. In addition, the testosterone level was slightly
      reduced in the serum. In the mammary fat pad, AhR appeared to regulate estrogen
      signaling because, in AhR-/- males, there was significant growth of the mammary
      ducts with high expression of ERalpha in the ductal epithelium. The enhanced
      mammary ductal growth appears to be related to overexpression of ERalpha
      accompanied by a high proliferation index, whereas the reduced fertility appears
      to be related defects in Notch signaling that leads to reduced expression of HES1
      and, consequently, early maturation of spermatocytes and a depletion of primary
      spermatids. Previous reports have indicated that AhR pathway is associated with
      infertility in men. Our results provide a mechanistic explanation for this
      defect.

PMID- 27688770
TI  - A High-Throughput Size Exclusion Chromatography Method to Determine the Molecular
      Size Distribution of Meningococcal Polysaccharide Vaccine.
AB  - Molecular size distribution of meningococcal polysaccharide vaccine is a readily
      identifiable parameter that directly correlates with the immunogenicity. In this
      paper, we report a size exclusion chromatography method to determine the
      molecular size distribution and distribution coefficient value of meningococcal
      polysaccharide serogroups A, C, W, and Y in meningococcal polysaccharide (ACWY)
      vaccines. The analyses were performed on a XK16/70 column packed with sepharose
      CL-4B with six different batches of Ingovax(r) ACWY, a meningococcal
      polysaccharide vaccine produced by Incepta Vaccine Ltd., Bangladesh. A
      quantitative rocket immunoelectrophoresis assay was employed to determine the
      polysaccharide contents of each serogroup. The calculated distribution
      coefficient values of serogroups A, C, W, and Y were found to be 0.26 +/- 0.16,
      0.21 +/- 0.11, 0.21 +/- 0.11, and 0.14 +/- 0.12, respectively, and met the
      requirements of British Pharmacopeia. The method was proved to be robust for
      determining the distribution coefficient values which is an obligatory
      requirement for vaccine lot release. 

PMID- 27688772
TI  - Herbal Medicines and Ovarian Hyperstimulation Syndrome: A Retrospective Cohort
      Study.
AB  - Background. The aim of this study was to assess the association between herbal
      medication and OHSS. Methods. This retrospective cohort study was conducted with
      101 polycystic ovary syndrome patients. 66 patients took conventional
      pharmacological medications and 35 took herbal medications. Data were analyzed by
      statistical test including Fisher's Exact and binominal logistic regression. P <
      0.05 was considered significant. Results. Of the 101 females, 53 were married and
      48 were single. There was no significant association between the groups in
      marriage. No significant association was found in mean age between the two groups
      (23.9 +/- 5.8 years in the control group versus 26.3 +/- 6.7 years in the case
      group). There was a significant difference between the two groups .After adding
      the dependent (OHSS prevalence) and independent (marriage and group) variables
      into the model, the Hosmer-Lemeshow test showed suitability. Variances analyzed
      with this model ranged between 29.4% and 40.7%. Conclusion. The indiscriminate
      use of herbs is correlated with OHSS. Because patients increasingly consume
      herbs, they should be aware of potential side effects. However, appropriate
      dosages of herbs could be obtained for use instead of conventional treatments,
      which often have side effects. 

PMID- 27688773
TI  - Defining the extreme substrate specificity of Euonymus alatus diacylglycerol
      acetyltransferase, an unusual membrane-bound O-acyltransferase.
AB  - Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) synthesizes the
      unusually structured 3-acetyl-1,2-diacylglycerols (acetyl-TAG) found in the seeds
      of a few plant species. A member of the membrane-bound O-acyltransferase (MBOAT)
      family, EaDAcT transfers the acetyl group from acetyl-CoA to sn-1,2
      diacylglycerol (DAG) to produce acetyl-TAG. In vitro assays demonstrated that the
      enzyme is also able to utilize butyryl-CoA and hexanoyl-CoA as acyl donors,
      though with much less efficiency compared with acetyl-CoA. Acyl-CoAs longer than
      eight carbons were not used by EaDAcT. This extreme substrate specificity of
      EaDAcT distinguishes it from all other MBOATs which typically catalyze the
      transfer of much longer acyl groups. In vitro selectivity experiments revealed
      that EaDAcT preferentially acetylated DAG molecules containing more double bonds
      over those with less. However, the enzyme was also able to acetylate saturated
      DAG containing medium chain fatty acids, albeit with less efficiency.
      Interestingly, EaDAcT could only acetylate the free hydroxyl group of sn-1,2-DAG
      but not the available hydroxyl groups in sn-1,3-DAG or in monoacylglycerols
      (MAG). Consistent with its similarity to the jojoba wax synthase, EaDAcT could
      acetylate fatty alcohols in vitro to produce alkyl acetates. Likewise, when
      coexpressed in yeast with a fatty acyl-CoA reductase capable of producing fatty
      alcohols, EaDAcT synthesized alkyl acetates although the efficiency of production
      was low. This improved understanding of EaDAcT specificity confirms that the
      enzyme preferentially utilizes acetyl-CoA to acetylate sn-1,2-DAGs and will be
      helpful in engineering the production of acetyl-TAG with improved functionality
      in transgenic plants.

PMID- 27688774
TI  - Successful Tocilizumab Therapy for Macrophage Activation Syndrome Associated with
      Adult-Onset Still's Disease: A Case-Based Review.
AB  - We report the case of a 71-year-old Japanese woman with adult-onset Still's
      disease (AOSD) in whom macrophage activation syndrome (MAS) developed despite
      therapy with oral high-dose prednisolone and intravenous methylprednisolone pulse
      therapy twice. She was successfully treated with tocilizumab (TCZ). Soon
      afterward, her fever ceased and high levels of both ferritin and C-reactive
      protein levels decreased. Her course was complicated by disseminated
      intravascular coagulation, cytomegalovirus infection, and Pneumocystis jirovecii
      pneumonia. After these were resolved, AOSD-associated MAS was well controlled.
      She was discharged on hospital day 87. Although biologics such as TCZ are
      becoming established for the treatment of AOSD, there is no recommended therapy
      for AOSD-associated MAS. Several biologics have been tried for this complication,
      but their efficacy and safety remain controversial. We reviewed reported cases of
      AOSD-associated MAS successfully treated with various biologics. TCZ initiation
      after adequate nonselective immunosuppressive therapy, such as methylprednisolone
      pulse therapy or a prednisolone-based combination of immunosuppressants, can be
      an effective treatment for AOSD-associated MAS. On the other hand, biologics
      given after insufficient immunosuppressive therapy may cause MAS. A strategy
      combining adequate immunosuppression and a biologic could be safe if special
      attention is given to adverse events such as opportunistic infections or biologic
      associated MAS. 

PMID- 27688775
TI  - High-Fidelity Reprogrammed Human IPSCs Have a High Efficacy of DNA Repair and
      Resemble hESCs in Their MYC Transcriptional Signature.
AB  - Human induced pluripotent stem cells (hiPSCs) are reprogrammed from adult or
      progenitor somatic cells and must make substantial adaptations to ensure genomic
      stability in order to become "embryonic stem cell- (ESC-) like." The DNA damage
      response (DDR) is critical for maintenance of such genomic integrity. Herein, we
      determined whether cell of origin and reprogramming method influence the DDR of
      hiPSCs. We demonstrate that hiPSCs derived from cord blood (CB) myeloid
      progenitors (i.e., CB-iPSC) via an efficient high-fidelity stromal-activated (sa)
      method closely resembled hESCs in DNA repair gene expression signature and
      irradiation-induced DDR, relative to hiPSCs generated from CB or fibroblasts via
      standard methods. Furthermore, sa-CB-iPSCs also more closely resembled hESCs in
      accuracy of nonhomologous end joining (NHEJ), DNA double-strand break (DSB)
      repair, and C-MYC transcriptional signatures, relative to standard hiPSCs. Our
      data suggests that hiPSCs derived via more efficient reprogramming methods
      possess more hESC-like activated MYC signatures and DDR signaling. Thus, an
      authentic MYC molecular signature may serve as an important biomarker in
      characterizing the genomic integrity in hiPSCs. 

PMID- 27688776
TI  - Characterization of Neurogenic Potential of Dental Pulp Stem Cells Cultured in
      Xeno/Serum-Free Condition: In Vitro and In Vivo Assessment.
AB  - Neural stem cells (NSCs) have a high potency for differentiation to neurons and
      glial cells for replacement of damaged cells and paracrine effects for the
      regeneration and remyelination of host axons. Dental pulp is known to have a
      potential to differentiate into neural-like cells; therefore, dental pulp may be
      used as an autologous cell source for neural repair. In this study, we
      selectively expanded stem cells from human dental pulp in an initial culture
      using NSC media under xeno- and serum-free conditions. At the initial step of
      primary culture, human dental pulp was divided into two groups according to the
      culture media: 10% fetal bovine serum medium group (FBS group) and NSC culture
      medium group (NSC group). In the NSC group relative to the FBS group, the
      expression of NSC markers and the concentrations of leukemia inhibitory factor,
      nerve growth factor, and stem cell factor were higher, although their expression
      levels were lower than those of human fetal NSCs. The transplanted cells of the
      NSC group survived well within the normal brain and injured spinal cord of rats
      and expressed nestin and Sox2. Under the xeno- and serum-free conditions,
      autologous human dental pulp-derived stem cells might prove useful for clinical
      cell-based therapies to repair damaged neural tissues. 

PMID- 27688778
TI  - van Bekkum DW, van Noord MJ, Maat B, Dicke KA. Attempts at identification of
      hemopoietic stem cell in mouse. Blood. 1971;38(5):547-558.

PMID- 27688779
TI  - Myeloma CARs are rolling into the clinical arena.

PMID- 27688781
TI  - PolyP's many faces.

PMID- 27688780
TI  - A tip of the cap to procoagulant platelets.

PMID- 27688777
TI  - The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental
      Tissue Engineering.
AB  - Within the field of tissue engineering, natural tissues are reconstructed by
      combining growth factors, stem cells, and different biomaterials to serve as a
      scaffold for novel tissue growth. As adequate vascularization and innervation are
      essential components for the viability of regenerated tissues, there is a high
      need for easily accessible stem cells that are capable of supporting these
      functions. Within the human tooth and its surrounding tissues, different stem
      cell populations can be distinguished, such as dental pulp stem cells, stem cells
      from human deciduous teeth, stem cells from the apical papilla, dental follicle
      stem cells, and periodontal ligament stem cells. Given their straightforward and
      relatively easy isolation from extracted third molars, dental stem cells (DSCs)
      have become an attractive source of mesenchymal-like stem cells. Over the past
      decade, there have been numerous studies supporting the angiogenic,
      neuroprotective, and neurotrophic effects of the DSC secretome. Together with
      their ability to differentiate into endothelial cells and neural cell types, this
      makes DSCs suitable candidates for dental tissue engineering and nerve injury
      repair. 

PMID- 27688782
TI  - Morphology of Niemann-Pick type A metabolic storage disorder.

PMID- 27688783
TI  - Sun B, Shah B, Fiskus W, et al. Synergistic activity of BET protein antagonist
      based combinations in mantle cell lymphoma cells sensitive or resistant to
      ibrutinib. Blood. 2015;126(13):1565-1574.

PMID- 27688784
TI  - Wang L, Man N, Sun X-J, et al. Regulation of AKT signaling by Id1 controls
      t(8;21) leukemia initiation and progression. Blood. 2015;126(5):640-650.

PMID- 27688785
TI  - Validation of the English Version of the Scale for Psychosocial Factors in Food
      Allergy and the Relationship with Mental Health, Quality of Life, and Self
      Efficacy.
AB  - Background. The Scale for Psychosocial Factors in Food Allergy (SPS-FA) is based
      on the biopsychosocial model of health and was developed and validated in Chile
      to measure the interaction between psychological variables and allergy symptoms
      in the child. We sought to validate this scale in an English speaking population
      and explore its relationship with parental quality of life, self-efficacy, and
      mental health. Methods. Parents (n = 434) from the general population in the UK,
      who had a child with a clinical diagnosis of food allergy, completed the SPS-FA
      and validated scales on food allergy specific parental quality of life (QoL),
      parental self-efficacy, and general mental health. Findings. The SPS-FA had good
      internal consistency (alphas = .61-.86). Higher scores on the SPS-FA
      significantly correlated with poorer parental QoL, self-efficacy, and mental
      health. All predictors explained 57% of the variance in SPS-FA scores with QoL as
      the biggest predictor (beta = .52). Discussion. The SPS-FA is a valid scale for
      use in the UK and provides a holistic view of the impact of food allergy on the
      family. In conjunction with health-related QoL measures, it can be used by health
      care practitioners to target care for patients and evaluate psychological
      interventions for improvement of food allergy management. 

PMID- 27688787
TI  - Bioenergy and Breast Cancer: A Report on Tumor Growth and Metastasis.
AB  - As many as 80% of the 296,000 women and 2,240 men diagnosed with breast cancer in
      the United States will seek out complementary and alternative medicine (CAM)
      treatments. One such therapy is Healing Touch (HT), recognized by the National
      Center for Complementary and Integrative Health (NCCIH) as a treatment modality.
      Using a multiple experimental groups design, fifty-six six- to eight-week-old
      Balb/c mice were injected with 4T1 breast cancer tumor cells and randomly divided
      into intervention and positive control groups. Five days after tumor cell
      injection, mice in the intervention groups received HT either daily or every
      other day for 10 minutes by one HT practitioner. At 15 days after tumor cell
      injection, tumor size was measured, and metastasis was evaluated by a medical
      pathologist after necropsy. Tumor size did not differ significantly among the
      groups (F(3,52) = 0.75, p value = 0.53). The presence of metastasis did not
      differ across groups (chi-square(3) = 3.902, p = 0.272) or when compared within
      an organ (liver: chi-square(3) = 2.507, p = 0.474; lungs: chi-square(3) = 3.804,
      p = 0.283; spleen: chi-square(3) = 0.595, p = 0.898). However, these results did
      indicate a moderate, though insignificant, positive impact of HT and highlight
      the need for continued research into dose, length of treatment, and measurable
      outcomes (tumor size, metastasis) to provide evidence to suggest application for
      nursing care. 

PMID- 27688786
TI  - Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal
      and pharmacokinetic profiles: a pilot study in children with congenital adrenal
      hyperplasia.
AB  - BACKGROUND: Little is known about the comparative effects of different
      glucocorticoids on the adrenal and growth hormone (GH) axes in children with
      congenital adrenal hyperplasia (CAH). We sought to compare the effects of
      hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with
      classic CAH and to investigate a potential role of pharmacogenetics. METHODS:
      Subjects were randomly assigned to three sequential 6-week courses of HC, PDN,
      and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body
      mass index (BMI). Single nucleotide polymorphism (SNP) analysis of genes in the
      glucocorticoid pathway was also performed. RESULTS: Nine prepubertal subjects
      aged 8.1 +/- 2.3 years completed the study. Mean ACTH, androstenedione, and 17
      hydroxyprogesterone (17-OHP) values were lower following the DEX arm of the study
      than after subjects received HC (p <= 0.016) or PDN (p <= 0.002). 17-OHP was also
      lower after HC than PDN (p < 0.001). There was no difference in IGF-1, GH, or
      change in BMI. SNP analysis revealed significant associations between hormone
      concentrations, pharmacokinetic parameters, and variants in several
      glucocorticoid pathway genes (ABCB1, NR3C1, IP013, GLCCI1). CONCLUSIONS: DEX
      resulted in marked adrenal suppression suggesting that its potency relative to
      hydrocortisone and prednisone was underestimated. SNPs conferred significant
      differences in responses between subjects. Although preliminary, these pilot data
      suggest that incorporating pharmacogenetics has the potential to eventually lead
      to targeted therapy in children with CAH.

PMID- 27688788
TI  - Baicalin Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension to Improve
      Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway
      and MMP-9.
AB  - Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in
      rats, but the mechanism of this effect remains unclear. Thus, investigating the
      potential mechanism of this effect was the aim of the present study. Model rats
      that display hypoxic pulmonary hypertension and cor pulmonale under control
      conditions were successfully generated. We measured a series of indicators to
      observe the levels of pulmonary arterial hypertension, pulmonary arteriole
      remodeling, and right ventricular remodeling. We assessed the activation of p38
      mitogen-activated protein kinase (MAPK) in the pulmonary arteriole walls and
      pulmonary tissue homogenates using immunohistochemistry and western blot
      analyses, respectively. The matrix metalloproteinase- (MMP-) 9 protein and mRNA
      levels in the pulmonary arteriole walls were measured using immunohistochemistry
      and in situ hybridization. Our results demonstrated that baicalin not only
      reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue
      homogenates but also downregulated the protein and mRNA expression levels of MMP
      9 in the pulmonary arteriole walls. This downregulation was accompanied by the
      attenuation of pulmonary hypertension, arteriole remodeling, and right
      ventricular remodeling. These results suggest that baicalin may attenuate
      pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia,
      by downregulating the p38 MAPK/MMP-9 pathway. 

PMID- 27688790
TI  - Herb-Drug Interaction: Effects of Relinqing(r) Granule on the Pharmacokinetics of
      Ciprofloxacin, Sulfamethoxazole, and Trimethoprim in Rats.
AB  - Relinqing granule (RLQ) is the best-selling Chinese patent drug for treatment of
      urinary system diseases. In this study, the effects of RLQ on the
      pharmacokinetics of ciprofloxacin, sulfamethoxazole, and trimethoprim in SD rats
      were investigated. Rats were randomly divided into control group 1, control group
      2, RLQ group 1, and RLQ group 2. RLQ group 1 and RLQ group 2 were treated orally
      with RLQ for 7 days, and rats were treated with the same volume of water in
      control group 1 and control group 2. Then, RLQ group 1 and control group 1 were
      given intragastrically ciprofloxacin on day 8, while RLQ group 2 and control
      group 2 were given intragastrically sulfamethoxazole and trimethoprim on day 8.
      Blood samples were collected and determined. There was no significant influence
      of pharmacokinetic parameters of trimethoprim on two groups. But some
      pharmacokinetic parameters of ciprofloxacin and sulfamethoxazole in RLQ
      pretreated rats were evidently altered (P < 0.05), which indicated that
      absorption of ciprofloxacin and sulfamethoxazole in RLQ pretreated rats was
      significantly affected. It indicated the coadministration of RLQ would have an
      influence on the efficacy of ciprofloxacin and sulfamethoxazole, and the doses of
      ciprofloxacin tablet and compound sulfamethoxazole tablet need adjustment. 

PMID- 27688789
TI  - Application of Traditional Chinese Medical Herbs in Prevention and Treatment of
      Respiratory Syncytial Virus.
AB  - Respiratory syncytial virus (RSV) is a common viral pathogen of the lower
      respiratory tract, which, in the absence of effective management, causes millions
      of cases of severe illness per year. Many of these infections develop into fatal
      pneumonia. In a review of English and Chinese medical literature, recent
      traditional Chinese medical herb- (TCMH-) based progress in the area of
      prevention and treatment was identified, and the potential anti-RSV compounds,
      herbs, and formulas were explored. Traditional Chinese medical herbs have a
      positive effect on inhibiting viral attachment, inhibiting viral internalization,
      syncytial formation, alleviation of airway inflammation, and stimulation of
      interferon secretion and immune system; however, the anti-RSV mechanisms of TCMHs
      are complicated, which should be further investigated. 

PMID- 27688791
TI  - Acupuncture Decreases Blood Pressure Related to Hypothalamus Functional
      Connectivity with Frontal Lobe, Cerebellum, and Insula: A Study of Instantaneous
      and Short-Term Acupuncture Treatment in Essential Hypertension.
AB  - The therapeutic effects of acupuncture in decreasing blood pressure are ambiguous
      and underlying acupuncture in hypertension treatment has not been investigated.
      Our objective was to observe the change of quality of life and compare the
      differences in brain functional connectivity by investigating instantaneous and
      short-term acupuncture treatment in essential hypertension patients. A total of
      30 patients were randomly divided into the LR3 group and sham acupoint group.
      Subjects received resting-state fMRI among preacupuncture, postinstantaneous, and
      short-term acupuncture treatment in two groups. Hypothalamus was selected as the
      seed point to analyze the changes in connectivity. We found three kinds of
      results: (1) There was statistical difference in systolic blood pressure in LR3
      group after the short-term treatment and before acupuncture. (2) Compared with
      sham acupoint, acupuncture at LR3 instantaneous effects in the functional
      connectivity with seed points was more concentrated in the frontal lobe. (3)
      Compared with instantaneous effects, acupuncture LR3 short-term effects in the
      functional connectivity with seed points had more regions in frontal lobe,
      cerebellum, and insula. These brain areas constituted a neural network structure
      with specific functions that could explain the mechanism of therapy in
      hypertension patients by LR3 acupoint. 

PMID- 27688792
TI  - Effect of Heweianshen Decoction on Orexin-A and Cholecystokinin-8 Expression in
      Rat Models of Insomnia.
AB  - Objective. To study the effect of Heweianshen decoction (HAD) on orexin-A and
      cholecystokinin-8 (CCK-8) expression in rat models of insomnia caused by
      injecting parachlorophenylalanine (PCPA) intraperitoneally. Methods. Fifty male
      Wistar rats were randomly divided into five groups (10 rats in each group): blank
      group, model group, and low-, medium-, and high-dose HAD-treated groups. A rat
      model of insomnia was established by injecting intraperitoneally with PCPA (300
      mg/kg body weight). Rats were given normal saline (10 mL/kg) or 5.25, 10.5, and
      21 g/kg HAD by intragastric administration once a day for 6 days. After that, the
      rats were sacrificed to collect the hypothalamus for tests, using
      radioimmunoassay to detect the expression of orexin-A and CCK-8. Results.
      Heweianshen decoction reduced the expression of orexin-A and increased the
      expression of CCK-8 in the hypothalamus of rat model of insomnia. Conclusion. The
      therapeutic effect of HAD on insomnia is partially attributed to the decreased
      expression of orexin-A and increased expression of CCK-8. 

PMID- 27688793
TI  - Nutritional status and its effect on treatment outcome among HIV infected clients
      receiving HAART in Ethiopia: a cohort study.
AB  - PURPOSES: The aim of this study was to determine the effects of nutritional
      status at the start of highly active anti-retroviral therapy on treatment
      outcomes among HIV/AIDS patients taking HAART at Jimma University Specialized
      Hospital. METHODS: We performed a retrospective cohort study involving 340 adults
      who started highly active anti-retroviral therapy. The patients have been
      clinically followed for 2 years. Data were extracted from paper based medical
      charts by trained data collectors from January 30 to February 28, 2014 using data
      collection format. We entered data into Epi data version 3.1 and then exported to
      SPSS for windows version 21. Predictors of CD4 change were identified using
      multivariable linear regression model. Time to an event (death) was estimated by
      Kaplan-Meier and predictors of mortality were identified by Cox proportional
      hazard model. RESULTS: Out of 340 patients, 42 patients died during the follow
      up. Twenty-five (59.5 %) deaths were from malnourished group. Age, baseline CD4,
      sex, baseline HAART and marital status were significant predictors of immunologic
      recovery at different time points. Malnutrition was associated with lower CD4
      recovery and greater hazard of death. CONCLUSIONS: Malnutrition tends to decrease
      CD4 recovery and predisposes patient to early death.

PMID- 27688794
TI  - Targeting vulnerable populations: a synthetic review on alcohol use and risky
      sexual behaviour among migrant populations.
AB  - BACKGROUND: Research has demonstrated a link between alcohol use and risky sexual
      behaviour among different types of migrant populations. Therefore, research
      investigating risk factors associated with alcohol consumption among them is a
      public health priority. This review aimed to explore the intersection between
      migration, alcohol consumption and risky sexual behaviour. METHODS: This article
      is a synthetic review of empirical studies on the association of alcohol and high
      risk sexual behaviour among different types of the migrant populations, focusing
      on measurable outcomes generated from quantitative data. A descriptive analysis
      generated from global and situational studies was used to interpret the reviewed
      research and to discuss critically the factors that drive migrants to engage in
      alcohol consumption and high-risk behaviour. RESULTS: This review found out that
      there is a significant and positive association between global and situational
      alcohol use and several outcomes of risky sexual behaviour among different types
      of migrant populations. This association was however mainly observed at high
      quantities and frequencies of alcohol use, mainly among male migrants, and was
      often tied to a specific situation or context, for instance the type of sexual
      partner, the level of mobility and to environmental factors such as living
      arrangements and entertainment venues. CONCLUSIONS: The study supports previous
      research that alcohol use is associated with risky sexual behaviour among
      different types of migrant populations. Therefore, future interventions should
      target mobile, male migrant heavy drinkers. Additional research is needed using
      more event-level and longitudinal methodologies that overcome prior
      methodological limitations.

PMID- 27688796
TI  - Analysis of gene copy number changes in tumor phylogenetics.
AB  - BACKGOUND: Evolution of cancer cells is characterized by large scale and rapid
      changes in the chromosomal  landscape. The fluorescence in situ hybridization
      (FISH) technique provides a way to measure the copy numbers of preselected genes
      in a group of cells and has been found to be a reliable source of data to model
      the evolution of tumor cells. Chowdhury et al. (Bioinformatics 29(13):189-98, 23;
      PLoS Comput Biol 10(7):1003740, 24) recently develop a computational model for
      tumor progression driven by gains and losses in cell count patterns obtained by
      FISH probes. Their model aims to find the rectilinear Steiner minimum tree (RSMT)
      (Chowdhury et al. in Bioinformatics 29(13):189-98, 23) and the duplication
      Steiner minimum tree (DSMT) (Chowdhury et al. in PLoS Comput Biol 10(7):1003740,
      24) that describe the progression of FISH cell count patterns over its branches
      in a parsimonious manner. Both the RSMT and DSMT problems are NP-hard and
      heuristics are required to solve the problems efficiently. METHODS: In this paper
      we propose two approaches to solve the RSMT problem, one inspired by iterative
      methods to address the "small phylogeny" problem (Sankoff et al. in J Mol Evol
      7(2):133-49, 27; Blanchette et al. in Genome Inform 8:25-34, 28), and the other
      based on maximum parsimony phylogeny inference. We further show how to extend
      these heuristics to obtain solutions to the DSMT problem, that models large scale
      duplication events. RESULTS: Experimental results from both simulated and real
      tumor data show that our methods outperform previous heuristics (Chowdhury et al.
      in Bioinformatics 29(13):189-98, 23; Chowdhury et al. in PLoS Comput Biol
      10(7):1003740, 24) in obtaining solutions to both RSMT and DSMT problems.
      CONCLUSION: The methods introduced here are able to provide more parsimony
      phylogenies compared to earlier ones which are consider better choices.

PMID- 27688797
TI  - Narrative descriptions of miyo-mahcihoyan (physical, emotional, mental, and
      spiritual well-being) from a contemporary nehiyawak (Plains Cree) perspective.
AB  - BACKGROUND: There are unequivocal health disparities, both physical and mental,
      between the Indigenous and non-Indigenous peoples of Canada. METHODS: Utilizing
      narrative inquiry, 15 nehiyawak (Plains Cree people) between 18 and 71 years of
      age from Thunderchild First Nation were interviewed to explore what improved
      their mental health and well-being and what they needed to attain optimal mental
      health and well-being. By posing questions that focused on the positive, the
      strengths and resilience of the nehiyawak came to the forefront. RESULTS:
      Narrative thematic analysis of interview data consistently revealed four
      overarching themes that highlighted what positively impacted nehiyawak mental
      health and well-being and their perceived needs to attain optimal mental health
      and well-being: relationships; spiritual beliefs and cultural practices; tanisisi
      wapahtaman pimatisiwin (worldview); and ekwa ohi kikwaya piko ka-ispayiki kispin
      ka-nohte-miyo-mahcihoyan (these are the things that need to happen if I want to
      be healthy). The nehiyawak in this study described holistic health determinants
      that correlate with the medicine wheel and the determinants of health, and
      described these holistic health determinants as making a positive difference to
      their mental health and as necessary for them to obtain optimal mental health and
      well-being. CONCLUSIONS: These results suggest that mental health programming and
      interventions should be harmonious with Indigenous culture; utilize a holistic
      approach that takes physical, emotional, mental, and spiritual well-being into
      consideration; and address the existing mental health disparities using the
      determinants of health as a framework, with an increased focus on the current
      socio-economic status of Indigenous peoples in Canada.

PMID- 27688795
TI  - Fungal cell wall agents and bacterial lipopolysaccharide in organic dust as
      possible risk factors for pulmonary sarcoidosis.
AB  - BACKGROUND: Composition of organic dust is very complex, involving particles of
      microbial, animal and plant origin. Several environmental exposure studies
      associate microbial cell wall agents in organic dust with various respiratory
      symptoms and diseases. The aim of the present study was to investigate the in
      vitro effects of the co-exposure of fungal cell wall agents (FCWAs) and bacterial
      lipopolysaccharide (LPS) on inflammatory immune responses of peripheral blood
      mononuclear cells (PBMCs) from patients with pulmonary sarcoidosis. METHODS:
      PBMCs from 22 patients with pulmonary sarcoidosis and 20 healthy subjects were
      isolated and stimulated in vitro with FCWAs (soluble and particulate (1 -> 3)
      beta-D-glucan, zymosan and chitosan) and/or LPS. Subsequently, cytokines were
      measured by ELISA and the mRNA expression of dectin-1, toll-like receptor 2
      (TLR2), TLR4 and mannose receptor (MR) was analysed by real-time RT-PCR. RESULTS:
      Patients with sarcoidosis had a significantly higher secretion of inflammatory
      cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10
      and IL-12 (1.7-fold, 2.0-fold, 2.2-fold, and 2.8-fold, respectively; all p <
      0.05) after in vitro co-stimulation of PBMCs with FCWAs and LPS. We showed that
      PBMCs from patients with sarcoidosis had a higher baseline mRNA expression of
      dectin-1, TLR2, TLR4 and MR (6-fold, 11-fold, 18-fold, and 4-fold, respectively).
      Furthermore, we found a reduced expression of dectin-1, TLR2 and TLR4 after
      stimulation with FCWAs and/or LPS, although the reduction was significantly
      weaker in patients than in healthy subjects. CONCLUSIONS: In conclusion, co
      stimulation with FCWAs and LPS of PBMC from patients with sarcoidosis caused a
      weaker reduction of dectin-1, TLR2, TLR4 receptors expression, which could
      increase the sensitivity of PBMCs, leading to excessive inflammatory cytokine
      responses and result in the development or progression of pulmonary sarcoidosis.

PMID- 27688798
TI  - Feasibility of an interactive voice response system for monitoring depressive
      symptoms in a lower-middle income Latin American country.
AB  - BACKGROUND: Innovative, scalable solutions are needed to address the vast unmet
      need for mental health care in low- and middle-income countries (LMICs). METHODS:
      We conducted a feasibility study of a 14-week automated telephonic interactive
      voice response (IVR) depression self-care service among Bolivian primary care
      patients with at least moderately severe depressive symptoms. We analyzed IVR
      call completion rates, the reliability and validity of IVR-collected data, and
      participant satisfaction. RESULTS: Of the 32 participants, the majority were
      women (78 % or 25/32) and non-indigenous (75 % or 24/32). Participants had
      moderate depressive symptoms at baseline (PHQ-8 score mean 13.3, SD = 3.5) and
      reported good or fair general health status (88 % or 28/32). Fifty-four percent
      of weekly IVR calls (approximately 7 out of 13 active call-weeks) were completed.
      Neither PHQ-8 scores nor IVR call completion differed significantly by ethnicity,
      education, self-reported depression diagnosis, self-reported overall health,
      number of chronic conditions, or health literacy. The reliability for IVR
      collected PHQ-8 scores was good (Cronbach's alpha = 0.83). Virtually every
      participant (97 %) was "mostly" or "very" satisfied with the program. Many
      described the program as beneficial for their mood and self-care, albeit limited
      by some technological difficulties and the lack of human interaction. CONCLUSION:
      Findings suggest that IVR could feasibly be used to provide monitoring and self
      care education to depressed patients in Bolivia. An expanded stepped-care service
      offering contact with lay health workers for more depressed individuals and
      expanded mHealth content may foster greater patient engagement and enhance its
      therapeutic value while remaining cost-effective. Trial registration ISRCTN
      ISRCTN 18403214. Registered 14 September 2016. Retrospectively registered.

PMID- 27688800
TI  - New journal structure of child and adolescent psychiatry and mental health.

PMID- 27688799
TI  - The associations of cumulative adverse childhood experiences and irritability
      with mental disorders in detained male adolescent offenders.
AB  - BACKGROUND: Adverse childhood experiences (ACEs) and psychiatric disorders are
      common in juvenile detainees. Emotional dysregulation resulting from cumulated
      ACEs may be characterized by symptoms of irritability. The present study examined
      whether the accumulation of ACEs, irritability, or both predicted mental
      disorders in incarcerated adolescents with and without controlling for one
      another and for socio-demographic factors. METHODS: One hundred thirty male
      detained juvenile offenders (aged 13.8-19.5 years) were assessed by structured
      clinical interviews and a self-reporting scale for irritability. Univariate and
      multivariate regression models were used to examine the shared and distinct
      associations of ACEs and irritability with psychiatric diagnoses. RESULTS: A
      total of 75 % of the participants reported more than one ACE. The ACE total score
      was positively related to self-reported irritability. The ACE total score
      predicted depressive disorders, suicidality, post-traumatic stress disorder
      (PTSD), and anxiety disorders. Irritability was positively related to depressive
      disorders, suicidality, disruptive behavior disorder (DBD), substance use
      disorder (SUD), and attention deficit hyperactivity disorder (ADHD). These
      associations remained significant in multivariate models. CONCLUSIONS: This study
      provides evidence for the predictive impact of self-reported ACEs and
      irritability with regard to adolescent psychiatric disorders in young male
      inmates. Both variables differed in their predictive power for PTSD,
      internalizing, and externalizing disorders indicating the need for specific
      therapeutic interventions. Taking a close look at their trauma history seems to
      be of special importance for juveniles suffering from PTSD and anxiety disorders.
      For delinquent adolescents with DBD, ADHD and SUD, the training of emotion
      regulation techniques appears most promising. Approaches focusing on both, ACEs
      and emotion-focused contents may be implemented in the treatment of depressive
      disorders and suicidality.

PMID- 27688801
TI  - Design and integration of a problem-based biofabrication course into an
      undergraduate biomedical engineering curriculum.
AB  - BACKGROUND: The rapidly evolving discipline of biological and biomedical
      engineering requires adaptive instructional approaches that teach students to
      target and solve multi-pronged and ill-structured problems at the cutting edge of
      scientific research. Here we present a modular approach to designing a lab-based
      course in the emerging field of biofabrication and biological design, leading to
      a final capstone design project that requires students to formulate and test a
      hypothesis using the scientific method. RESULTS: Students were assessed on a
      range of metrics designed to evaluate the format of the course, the efficacy of
      the format for teaching new topics and concepts, and the depth of the
      contribution this course made to students training for biological engineering
      careers. The evaluation showed that the problem-based format of the course was
      well suited to teaching students how to use the scientific method to investigate
      and uncover the fundamental biological design rules that govern the field of
      biofabrication. CONCLUSIONS: We show that this approach is an efficient and
      effective method of translating emergent scientific principles from the lab bench
      to the classroom and training the next generation of biological and biomedical
      engineers for careers as researchers and industry practicians.

PMID- 27688802
TI  - Hydroxyurea: a new old therapy for Langerhans cell histiocytosis.

PMID- 27688803
TI  - Antigen modulation as a potential mechanism of anti-KEL immunoprophylaxis in
      mice.
AB  - Red blood cell (RBC) alloimmunization is a serious complication of transfusion or
      pregnancy. Despite the widespread use of Rh immune globulin to prevent pregnancy
      associated anti-D alloimmunization, its mechanism of action remains elusive. We
      have previously described a murine model in which immunoprophylaxis with
      polyclonal anti-KEL sera prevents alloimmunization in wild-type recipients
      transfused with transgenic murine RBCs expressing the human KEL glycoprotein. To
      investigate the mechanism of action, we have now evaluated the outcome of
      immunoprophylaxis treatment in mice lacking Fcgamma receptors (FcgammaRs),
      complement (C3), both, or none. Whereas polyclonal anti-KEL sera completely
      prevented alloimmunization in wild-type and single-knockout (KO) mice lacking
      FcgammaRs or C3, double-KO mice lacking both FcgammaRs and C3 became
      alloimmunized despite immunoprophylaxis. Rapid clearance of essentially all
      transfused RBCs with detectable KEL glycoprotein antigen occurred within 24 hours
      in wild-type and single-KO recipients treated with immunoprophylaxis, with the
      transfused RBCs remaining in circulation having minimal KEL glycoprotein antigen
      detectable by flow cytometry or western blot. In contrast, transfused RBCs with
      the KEL glycoprotein antigen fully intact continued to circulate for days in
      double-KO mice despite treatment with immunoprophylaxis. Further, in vitro
      phagocytosis assays showed no consumption of opsonized murine RBCs by double-KO
      splenocytes. Taken in combination, our data suggest that modulation of the KEL
      antigen (and potentially RBC clearance) by redundant recipient pathways involving
      both FcgammaRs and C3 may be critical to the mechanism of action of polyclonal
      anti-KEL immunoprophylaxis. These findings could have implications for the
      development of immunoprophylaxis programs in humans.

PMID- 27688807
TI  - How to perform a root cause analysis for workup and future prevention of medical
      errors: a review.
AB  - Providing quality patient care is a basic tenant of medical and surgical
      practice. Multiple orthopaedic programs, including The Patient Safety Committee
      of the American Academy of Orthopaedic Surgeons (AAOS), have been implemented to
      measure quality of surgical care, as well as reduce the incidence of medical
      errors. Structured Root Cause Analysis (RCA) has become a recent area of interest
      and, if performed thoroughly, has been shown to reduce surgical errors across
      many subspecialties. There is a paucity of literature on how the process of a RCA
      can be effectively implemented. The current review was designed to provide a
      structured approach on how to conduct a formal root cause analysis. Utilization
      of this methodology may be effective in the prevention of medical errors. 

PMID- 27688806
TI  - Comparative genomic, transcriptomic and secretomic profiling of Penicillium
      oxalicum HP7-1 and its cellulase and xylanase hyper-producing mutant EU2106, and
      identification of two novel regulatory genes of cellulase and xylanase gene
      expression.
AB  - BACKGROUND: The filamentous fungus Penicillium oxalicum is a potential
      alternative to Trichoderma reesei for industrial production of a complete
      cellulolytic enzyme system for a bio-refinery. Comparative omics approaches can
      support rational genetic engineering and/or breeding of filamentous fungi with
      improved cellulase production capacity. In this study, comparative genomic,
      transcriptomic and secretomic profiling of P. oxalicum HP7-1 and its cellulase
      and xylanase hyper-producing mutant EU2106 were employed to screen for novel
      regulators of cellulase and xylanase gene expression. RESULTS: The 30.62 Mb P.
      oxalicum HP7-1 genome was sequenced, and 9834 protein-coding genes were
      annotated. Re-sequencing of the mutant EU2106 genome identified 274 single
      nucleotide variations and 12 insertion/deletions. Comparative genomic,
      transcriptomic and secretomic profiling of HP7-1 and EU2106 revealed four
      candidate regulators of cellulase and xylanase gene expression. Deletion of these
      candidate genes and measurement of the enzymatic activity of the resultant
      mutants confirmed the identity of three regulatory genes. POX02484 and POX08522,
      encoding a putative Zn(II)2Cys6 DNA-binding domain and forkhead protein,
      respectively, were found to be novel, while PoxClrB is an ortholog of ClrB, a key
      transcriptional regulator of cellulolytic enzyme gene expression in filamentous
      fungi. DeltaPOX02484 and DeltaPOX08522 mutants exhibited significantly reduced
      beta-glucosidase activity, increased carboxymethylcellulose cellulase and
      xylanase activities, and altered transcription level of cellulase and xylanase
      genes compared with the parent strain DeltaPoxKu70, with Avicel as the sole
      carbon source. CONCLUSIONS: Two novel genes, POX02484 and POX08522, were found
      and characterized to regulate the expression of cellulase and xylanase genes in
      P. oxalicum. These findings are important for engineering filamentous fungi to
      improve cellulase and xylanase production.

PMID- 27688804
TI  - Reversible binding of hemoglobin to band 3 constitutes the molecular switch that
      mediates O2 regulation of erythrocyte properties.
AB  - Functional studies have shown that the oxygenation state of the erythrocyte
      regulates many important pathways, including glucose metabolism, membrane
      mechanical stability, and cellular adenosine triphosphate (ATP) release.
      Deoxyhemoglobin (deoxyHb), but not oxyhemoglobin, binds avidly and reversibly to
      band 3, the major erythrocyte membrane protein. Because band 3 associates with
      multiple metabolic, solute transport, signal transduction, and structural
      proteins, the hypothesis naturally arises that the O2-dependent regulation of
      erythrocyte properties might be mediated by the reversible association of deoxyHb
      with band 3. To explore whether the band 3-deoxyHb interaction constitutes a
      "molecular switch" for regulating erythrocyte biology, we have generated
      transgenic mice with mutations in the deoxyHb-binding domain of band 3. One
      strain of mouse contains a "humanized" band 3 in which the N-terminal 45 residues
      of mouse band 3 are replaced by the homologous sequence from human band 3,
      including the normal human band 3 deoxyHb-binding site. The second mouse contains
      the same substitution as the first, except the deoxyHb site on band 3 (residues
      12-23) has been deleted. Comparison of these animals with wild-type mice
      demonstrates that the following erythrocyte properties are controlled by the O2
      dependent association of hemoglobin with band 3: (1) assembly of a glycolytic
      enzyme complex on the erythrocyte membrane which is associated with a shift in
      glucose metabolism between the pentose phosphate pathway and glycolysis, (2)
      interaction of ankyrin with band 3 and the concomitant regulation of erythrocyte
      membrane stability, and (3) release of ATP from the red cell which has been
      linked to vasodilation.

PMID- 27688805
TI  - Photosynthetic conversion of CO2 to farnesyl diphosphate-derived phytochemicals
      (amorpha-4,11-diene and squalene) by engineered cyanobacteria.
AB  - BACKGROUND: Metabolic engineering of cyanobacteria has enabled photosynthetic
      conversion of CO2 to value-added chemicals as bio-solar cell factories. However,
      the production levels of isoprenoids in engineered cyanobacteria were quite low,
      compared to other microbial hosts. Therefore, modular optimization of multiple
      gene expressions for metabolic engineering of cyanobacteria is required for the
      production of farnesyl diphosphate-derived isoprenoids from CO2. RESULTS: Here,
      we engineered Synechococcus elongatus PCC 7942 with modular metabolic pathways
      consisting of the methylerythritol phosphate pathway enzymes and the amorphadiene
      synthase for production of amorpha-4,11-diene, resulting in significantly
      increased levels (23-fold) of amorpha-4,11-diene (19.8 mg/L) in the best strain
      relative to a parental strain. Replacing amorphadiene synthase with squalene
      synthase led to the synthesis of a high amount of squalene (4.98 mg/L/OD730).
      Overexpression of farnesyl diphosphate synthase is the most critical factor for
      the significant production, whereas overexpression of 1-deoxy-d-xylulose 5
      phosphate reductase is detrimental to the cell growth and the production.
      Additionally, the cyanobacterial growth inhibition was alleviated by expressing a
      terpene synthase in S. elongatus PCC 7942 strain with the optimized MEP pathway
      only (SeHL33). CONCLUSIONS: This is the first demonstration of photosynthetic
      production of amorpha-4,11-diene from CO2 in cyanobacteria and production of
      squalene in S. elongatus PCC 7942. Our optimized modular OverMEP strain (SeHL33)
      with either co-expression of ADS or SQS demonstrated the highest production
      levels of amorpha-4,11-diene and squalene, which could expand the list of
      farnesyl diphosphate-derived isoprenoids from CO2 as bio-solar cell factories.

PMID- 27688809
TI  - Mediterranean diet in UK shows positive effects in study.

PMID- 27688808
TI  - 19p13.2 Microdeletion including NFIX associated with overgrowth and intellectual
      disability suggestive of Malan syndrome.
AB  - BACKGROUND: Overgrowth syndromes represent clinically and genetically
      heterogeneous conditions characterized by a wide spectrum of malformations, tall
      stature, intellectual disability and/or macrocephaly. RESULTS: In a cohort of
      four clinically characterized patients with overgrowth syndrome without known
      causative gene mutation, we performed an Illumina SNP-array analysis to identify
      the pathogenic copy number variations. We identified two rare copy number
      variations harboring overgrowth syndrome related genes. Patient 1 was Malan
      syndrome with a 1.4 Mb 19p13.2-13.13 microdeletion including NFIX, and Patient 2
      was identified as Sotos syndrome with a 1.6 Mb 5q35.2 microdeletion encompassing
      NSD1. CONCLUSIONS: We identified two patients associated with Manlan syndrome and
      Sotos syndrome respectively. We also discuss the use of the microarrays-based
      candidate gene strategy in Mendelian disease-gene identification.

PMID- 27688811
TI  - ProtNN: fast and accurate protein 3D-structure classification in structural and
      topological space.
AB  - BACKGROUND: Studying the functions and structures of proteins is important for
      understanding the molecular mechanisms of life. The number of publicly available
      protein structures has increasingly become extremely large. Still, the
      classification of a protein structure remains a difficult, costly, and time
      consuming task. The difficulties are often due to the essential role of spatial
      and topological structures in the classification of protein structures. RESULTS:
      We propose ProtNN, a novel classification approach for protein 3D-structures.
      Given an unannotated query protein structure and a set of annotated proteins,
      ProtNN assigns to the query protein the class with the highest number of votes
      across the k nearest neighbor reference proteins, where k is a user-defined
      parameter. The search of the nearest neighbor annotated structures is based on a
      protein-graph representation model and pairwise similarities between vector
      embedding of the query and the reference protein structures in structural and
      topological spaces. CONCLUSIONS: We demonstrate through an extensive experimental
      evaluation that ProtNN is able to accurately classify several datasets in an
      extremely fast runtime compared to state-of-the-art approaches. We further show
      that ProtNN is able to scale up to a whole PDB dataset in a single-process mode
      with no parallelization, with a gain of thousands order of magnitude in runtime
      compared to state-of-the-art approaches.

PMID- 27688810
TI  - The tip of the iceberg: challenges of accessing hospital electronic health record
      data for biological data mining.
AB  - Modern cohort studies include self-reported measures on disease, behavior and
      lifestyle, sensor-based observations from mobile phones and wearables, and rich 
      omics data. Follow-up is often achieved through electronic health record (EHR)
      linkages across primary and secondary healthcare providers. Historically however,
      researchers typically only get to see the tip of the iceberg: coded
      administrative data relating to healthcare claims which mainly record billable
      diagnoses and procedures. The rich data generated during the clinical pathway
      remain submerged and inaccessible. While some institutions and initiatives have
      made good progress in unlocking such deep phenotypic data within their
      institutional realms, access at scale still remains challenging. Here we outline
      and discuss the main technical and social challenges associated with accessing
      these data for data mining and hauling the entire iceberg. 

PMID- 27688812
TI  - Imprinted DNA methylation reconstituted at a non-imprinted locus.
AB  - BACKGROUND: In mammals, tight regulation of cytosine methylation is required for
      embryonic development and cellular differentiation. The trans-acting DNA
      methyltransferases that catalyze this modification have been identified and
      characterized; however, these proteins lack sequence specificity, leaving the
      mechanism of targeting unknown. A cis-acting regulator within the Rasgrf1
      imprinting control region (ICR) is necessary for establishment and maintenance of
      local imprinted methylation. Here, we investigate whether 3-kb of sequence from
      the Rasgrf1 ICR is sufficient to direct appropriate imprinted methylation and
      target gene expression patterns when ectopically inserted at the Wnt1 locus.
      RESULTS: The Rasgrf1 ICR at Wnt1 lacked somatic methylation when maternally
      transmitted and was fully methylated upon paternal transmission, consistent with
      its behavior at the Rasgrf1 locus. It was unmethylated in the female germline and
      was enriched for methylation in the male germline, though not to the levels seen
      at the endogenous Rasgrf1 allele. Wnt1 expression was not imprinted by the
      ectopic ICR, likely due to additional sequences being required for this function.
      CONCLUSIONS: We have identified sequences that are sufficient for partial
      establishment and full maintenance of the imprinted DNA methylation patterns.
      Because full somatic methylation can occur without full gametic methylation, we
      infer that somatic methylation of the Rasgrf1 ICR is not simply a consequence of
      maintained gametic methylation.

PMID- 27688815
TI  - Hormonal contraception use among teenagers linked to depression.

PMID- 27688814
TI  - Multilocus sequence typing of Campylobacter concisus from Danish diarrheic
      patients.
AB  - The emerging enteric pathogen Campylobacter concisus is associated with prolonged
      diarrhea and inflammatory bowel disease. Previous studies have shown that C.
      concisus strains are very genetically diverse. Nevertheless, C. concisus strains
      have been divided into two genomospecies, where GS1 strains have been isolated
      predominantly from healthy individuals, while the GS2 cluster consists of
      isolates primarily from diarrheic individuals. The aim of the present study was
      to determine the genetic diversity of C. concisus isolates from Danish diarrheic
      patients. Multilocus sequence typing using the loci aspA, atpA, glnA, gltA, glyA,
      ilvD and pgm, as well as genomospecies based on specific differences in the 23S
      rRNA, was used to characterize 67 isolates (63 fecal and 4 oral), from 49
      patients with different clinical presentations (29 with diarrhea, eight with
      bloody diarrhea, seven with collagenous colitis and five with Crohn's disease).
      MLST revealed a high diversity of C. concisus with 53 sequence types (STs), of
      which 52 were identified as 'new' STs. Allele sequences showed more than 90 %
      similarity between isolates, with only four outliers. Dendrogram profiles of each
      allele showed a division into two groups, which more or less correlated with
      genomospecies A and genomospecies B. However, in contrary to previous results,
      this subgrouping had no association to the clinical severity of disease. 

PMID- 27688813
TI  - A survey exploring self-reported indoor and outdoor footwear habits, foot
      problems and fall status in people with stroke and Parkinson's.
AB  - BACKGROUND: Ill-fitting shoes have been implicated as a risk factor for falls but
      research to date has focused on people with arthritis, diabetes and the general
      older population; little is known about people with neurological conditions. This
      survey for people with stroke and Parkinson's explored people's choice of indoor
      and outdoor footwear, foot problems and fall history. METHODS: Following ethical
      approval, 1000 anonymous postal questionnaires were distributed to health
      professionals, leads of Parkinson's UK groups and stroke clubs in the wider
      Southampton area, UK. These collaborators handed out survey packs to people with
      a confirmed diagnosis of stroke or Parkinson's. RESULTS: Three hundred and sixty
      three completed surveys were returned (218 from people with Parkinson's and 145
      from people with stroke). Most respondents wore slippers indoors and walking
      shoes outdoors and considered comfort and fit the most important factors when
      buying footwear. Foot problems were reported by 43 % (95 % confidence intervals
      36 to 52 %; stroke) and 53 % (95 % confidence interval 46 to 59 %; Parkinson's)
      of respondents; over 50 % had never accessed foot care support. Fifty percent of
      all respondents reported falls. In comparison to non-fallers, a greater
      proportion of fallers reported foot problems (57 %), with greater proportions
      reporting problems impacting on balance and influencing choice of footwear (p <
      0.01) in comparison to non-fallers in each case. Forty-seven percent of fallers
      with foot problems had not accessed foot care support. CONCLUSIONS: Many people
      with stroke and Parkinson's wear slippers indoors. A high percentage of these
      individuals reported both foot problems and falls impacting on footwear habits
      and choice of footwear; however many did not receive foot care support. These
      findings highlight that further exploration of footwear and foot problems in
      these populations is warranted to provide evidence based advice on safe and
      appropriate footwear to support rehabilitation and fall prevention.

PMID- 27688816
TI  - A Capillary Electrophoresis Electrospray Ionization-Mass Spectrometry Method
      using a Borate Background Electrolyte for the Fingerprinting Analysis of
      Flavonoids in Ginkgo biloba Herbal Supplements.
AB  - A laboratory-built sheath liquid capillary electrophoresis-mass spectrometry
      interface was used to develop a qualitative method for fingerprinting analysis of
      14 structurally similar flavones, flavonols, flavonones, and several
      representative glycosides in plant samples. The migration order of the flavonoids
      was dependent on a the number of hydroxyl groups present on the flavonoid B-ring,
      extent of conjugation, number of glycosidic functionalities, and ability of the
      flavonoid to form stable borate complexes with the background electrolyte. Parent
      ion scans of the flavonoids yielded [M-H]-, except for catechol containing
      flavonoids, which were detected as borate adducts. These adducts can be used
      diagnostically to determine the presence or absence of catechol groups on unknown
      polyphenolic compounds. Product ion scans of the flavonoid glycosides and borate
      adducts typically yielded the deprotonated aglycone fragment as the base peak,
      which could be used to confirm the base structure of the flavonoid. This method's
      utility was demonstrated by analyzing flavonoids present in ethanolic extracts of
      Ginkgo biloba herbal supplements.

PMID- 27688817
TI  - MSP-HTPrimer: a high-throughput primer design tool to improve assay design for
      DNA methylation analysis in epigenetics.
AB  - BACKGROUND: Bisulfite (BS) conversion-based and methylation-sensitive restriction
      enzyme (MSRE)-based PCR methods have been the most commonly used techniques for
      locus-specific DNA methylation analysis. However, both methods have advantages
      and limitations. Thus, an integrated approach would be extremely useful to
      quantify the DNA methylation status successfully with great sensitivity and
      specificity. Designing specific and optimized primers for target regions is the
      most critical and challenging step in obtaining the adequate DNA methylation
      results using PCR-based methods. Currently, no integrated, optimized, and high
      throughput methylation-specific primer design software methods are available for
      both BS- and MSRE-based methods. Therefore an integrated, powerful, and easy-to
      use methylation-specific primer design pipeline with great accuracy and success
      rate will be very useful. RESULTS: We have developed a new web-based pipeline,
      called MSP-HTPrimer, to design primers pairs for MSP, BSP, pyrosequencing, COBRA,
      and MSRE assays on both genomic strands. First, our pipeline converts all target
      sequences into bisulfite-treated templates for both forward and reverse strand
      and designs all possible primer pairs, followed by filtering for single
      nucleotide polymorphisms (SNPs) and known repeat regions. Next, each primer pairs
      are annotated with the upstream and downstream RefSeq genes, CpG island, and cut
      sites (for COBRA and MSRE). Finally, MSP-HTPrimer selects specific primers from
      both strands based on custom and user-defined hierarchical selection criteria.
      MSP-HTPrimer produces a primer pair summary output table in TXT and HTML format
      for display and UCSC custom tracks for resulting primer pairs in GTF format.
      CONCLUSIONS: MSP-HTPrimer is an integrated, web-based, and high-throughput
      pipeline and has no limitation on the number and size of target sequences and
      designs MSP, BSP, pyrosequencing, COBRA, and MSRE assays. It is the only
      pipeline, which automatically designs primers on both genomic strands to increase
      the success rate. It is a standalone web-based pipeline, which is fully
      configured within a virtual machine and thus can be readily used without any
      configuration. We have experimentally validated primer pairs designed by our
      pipeline and shown a very high success rate of primer pairs: out of 66 BSP primer
      pairs, 63 were successfully validated without any further optimization step and
      using the same qPCR conditions. The MSP-HTPrimer pipeline is freely available
      from http://sourceforge.net/p/msp-htprimer.

PMID- 27688818
TI  - The emerging role of lysine methyltransferase SETD8 in human diseases.
AB  - SETD8/SET8/Pr-SET7/KMT5A is the only known lysine methyltransferase (KMT) that
      monomethylates lysine 20 of histone H4 (H4K20) in vivo. Lysine residues of non
      histone proteins including proliferating cell nuclear antigen (PCNA) and p53 are
      also monomethylated. As a consequence, the methyltransferase activity of the
      enzyme is implicated in many essential cellular processes including DNA
      replication, DNA damage response, transcription modulation, and cell cycle
      regulation. This review aims to provide an overview of the roles of SETD8 in
      physiological and pathological pathways and to discuss the progress made to date
      in inhibiting the activity of SETD8 by small molecules, with an emphasis on their
      discovery, selectivity over other methyltransferases and cellular activity.

PMID- 27688820
TI  - Interrelation of Glycemic Status and Neuropsychiatric Disturbances in Farmers
      with Organophosphorus Pesticide Toxicity.
AB  - BACKGROUND: Diverse group of agro-chemicals are indiscriminately sprayed by the
      farmers for pest control to enhance crop yield. About 25 million agricultural
      workers in the developing world suffer from at least one episode of poisoning
      each year, mainly by anticholinesterase- like organophosphates (OPs). OBJECTIVE:
      The present study was aimed to establish the OP toxicity in 187 occupationally
      exposed pesticide sprayers of mango plantation in rural Malihabad, Lucknow, in
      terms of neuro-cognitive impairment, mental health status, clinical symptoms,
      diabetes, and hematological factors. METHOD: The exposed group was compared to
      187 pesticides-unexposed normal healthy persons engaged in normal usual
      agricultural work (age, sex and education corresponding to age group of selected
      subject group) from Rural Malihabad, Lucknow (India). Neuro-cognitive impairment
      was measured using the Subjective Neurocognition Inventory and mental health
      status using the General Health questionnaire-28. The subjects were also tested
      for biochemical and enzymatic parameters. RESULTS: The exposed farmers showed
      alterations in enzymatic and clinical parameters. While the rates of anxiety /
      insomnia and severe depression were also significantly higher in the pesticide
      sprayers, disorders affecting psychomotor speed, selective attention, divided
      attention, verbal memory, nonverbal memory, prospective memory, spatial
      functioning, and initiative/energy were all lower in the sprayers. Pesticide
      sprayers showed a number of clinical symptoms like eczema, saliva secretion,
      fatigue, headache, sweating, abdominal pain, nausea, superior distal muscle
      weakness, inferior distal muscle weakness, hand tingling and etc. which all
      significantly correlated with the number of working years. CONCLUSION: These
      findings suggested that farmers who work with OPs are prone to neuro
      psychological disorders and diabetes.

PMID- 27688819
TI  - DNA methylation and smoking in Korean adults: epigenome-wide association study.
AB  - BACKGROUND: Exposure to cigarette smoking can increase the risk of cancers and
      cardiovascular and pulmonary diseases. However, the underlying mechanisms of how
      smoking contributes to disease risks are not completely understood. Epigenome
      wide association studies (EWASs), mostly in non-Asian populations, have been
      conducted to identify smoking-associated methylation alterations at individual
      probes. There are few data on regional methylation changes in relation to
      smoking. Few data link differential methylation in blood to differential gene
      expression in lung tissue. RESULTS: We identified 108 significant (false
      discovery rate (FDR) < 0.05) differentially methylated probes (DMPs) and 87
      significant differentially methylated regions (DMRs) (multiple-testing corrected
      p < 0.01) in current compared to never smokers from our EWAS of cotinine
      validated smoking in blood DNA from a Korean chronic obstructive pulmonary
      disease cohort (n = 100 including 31 current, 30 former, and 39 never smokers)
      using Illumina HumanMethylation450 BeadChip. Of the 108 DMPs (FDR < 0.05), nine
      CpGs were statistically significant based on Bonferroni correction and 93 were
      novel including five that mapped to loci previously associated with smoking. Of
      the 87 DMRs, 66 were mapped to novel loci. Methylation correlated with urine
      cotinine levels in current smokers at six DMPs, with pack-years in current
      smokers at six DMPs, and with duration of smoking cessation in former smokers at
      eight DMPs. Of the 143 genes to which our significant DMPs or DMRs annotated,
      gene expression levels at 20 genes were associated with pack-years in lung tissue
      transcriptome data of smokers (Asan Biobank, n = 188). CONCLUSIONS: Our study of
      differential methylation in Koreans confirmed previous findings from non-Asian
      populations and revealed novel loci in relation to smoking. Smoking-related
      differential methylation in blood is associated with gene expression in lung
      tissue, an important target of adverse health effects of smoking, supporting the
      potential functional importance of methylation in smoking-related disease.

PMID- 27688821
TI  - Structural and Optical Properties of Discrete Dendritic Pt Nanoparticles on
      Colloidal Au Nanoprisms.
AB  - Catalytic and optical properties can be coupled by combining different metals
      into nanoscale architectures in which both the shape and the composition provide
      fine-tuning of functionality. Here, discrete, small Pt nanoparticles (diameter =
      3-6 nm) were grown in linear arrays on Au nanoprisms, and the resulting
      structures are shown to retain strong localized surface plasmon resonances.
      Multidimensional electron microscopy and spectroscopy techniques (energy
      dispersive X-ray spectroscopy, electron tomography, and electron energy-loss
      spectroscopy) were used to unravel their local composition, three-dimensional
      morphology, growth patterns, and optical properties. The composition and
      tomographic analyses disclose otherwise ambiguous details of the Pt-decorated Au
      nanoprisms, revealing that both pseudospherical protrusions and dendritic Pt
      nanoparticles grow on all faces of the nanoprisms (the faceted or occasionally
      twisted morphologies of which are also revealed), and shed light on the alignment
      of the Pt nanoparticles. The electron energy-loss spectroscopy investigations
      show that the Au nanoprisms support multiple localized surface plasmon resonances
      despite the presence of pendant Pt nanoparticles. The plasmonic fields at the
      surface of the nanoprisms indeed extend into the Pt nanoparticles, opening
      possibilities for combined optical and catalytic applications. These insights
      pave the way toward comprehensive nanoengineering of multifunctional bimetallic
      nanostructures, with potential applications in plasmon-enhanced catalysis and in
      situ monitoring of chemical processes via surface-enhanced spectroscopy.

PMID- 27688822
TI  - Engaging Communities in Research on Cumulative Risk and Social Stress-Environment
      Interactions: Lessons Learned from EPA's STAR Program.
AB  - Studies have documented cumulative health effects of chemical and nonchemical
      exposures, particularly chronic environmental and social stressors. Environmental
      justice groups have advocated for community participation in research that
      assesses how these interactions contribute to health disparities experienced by
      low-income and communities of color. In 2009, the U.S. Environmental Protection
      Agency issued a request for research applications (RFA), "Understanding the Role
      of Nonchemical Stressors and Developing Analytic Methods for Cumulative Risk
      Assessments." Seven research projects were funded to help address this knowledge
      gap. Each engaged with communities in different ways. We describe the community
      engagement approaches of the seven research projects, which ranged from outreach
      through shared leadership/participatory. We then assess the experiences of these
      programs with respect to the community engagement goals of the RFA. We present
      insights from these community engagement efforts, including how the grants helped
      to build or enhance the capacity of community organizations in addition to
      contributing to the research projects. Our analysis of project proposals, annual
      grantee reports, and participant observation of these seven projects suggests
      guidelines for the development of future funding mechanisms and for conducting
      community-engaged research on cumulative risk involving environmental and social
      stressors including: 1) providing for flexibility in the mode of community
      engagement; 2) addressing conflict between research timing and engagement needs,
      3) developing approaches for communicating about the uniquely sensitive issues of
      nonchemical stressors and social risks; and 4) encouraging the evaluation of
      community engagement efforts.

PMID- 27688823
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1941874415591500.].

PMID- 27688824
TI  - Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic
      Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via
      P38/JNK Signaling Pathways.
AB  - Obstructive sleep apnea (OSA) associated chronic kidney disease is mainly caused
      by chronic intermittent hypoxia (CIH) triggered tissue damage. Receptor for
      advanced glycation end product (RAGE) and its ligand high mobility group box 1
      (HMGB1) are expressed on renal cells and mediate inflammatory responses in OSA
      related diseases. To determine their roles in CIH-induced renal injury, soluble
      RAGE (sRAGE), the RAGE neutralizing antibody, was intravenously administered in a
      CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis.
      Rats were divided into four groups: (1) normal air (NA), (2) CIH, (3) CIH+sRAGE,
      and (4) NA+sRAGE. Our results showed that CIH accelerated renal histological
      injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-kappaB, TNF
      alpha, and IL-6), apoptotic (Bcl-2/Bax), and mitogen-activated protein kinases
      (phosphorylation of P38, ERK, and JNK) signal transduction pathways, which were
      abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by
      attenuating tubular endothelial apoptosis determined by immunofluorescence
      staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated
      chronic inflammatory transduction cascades that contributed to the pathogenesis
      of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE
      provided a therapeutic potential for CIH-induced renal injury, inflammation, and
      apoptosis through P38 and JNK pathways.

PMID- 27688825
TI  - Rosmarinic Acid and Melissa officinalis Extracts Differently Affect Glioblastoma
      Cells.
AB  - Lemon balm (Melissa officinalis L.) has many biological effects but especially
      important is its neuroprotective activity. The aim of the study is to produce
      different extracts of Melissa officinalis and analyse their chemical composition
      and biological properties on rat glioblastoma C6 cells. Results revealed that
      rosmarinic acid (RA) is the predominant compound of lemon balm extracts. RA has
      cytotoxic effect on glioblastoma cells (LC50 290.5 MUM after the incubation of 24
      h and LC50 171.3 MUM after 48 h). RA at concentration 80-130 MUM suppresses the
      cell proliferation and has an antioxidant effect. 200 MUM and higher
      concentrations of RA have a prooxidant effect and initiate cell death through
      necrosis. The aqueous extract of lemon balm is also enriched in phenolic
      compounds: protocatechuic, caftaric, caffeic, ferulic, and cichoric acids and
      flavonoid luteolin-7-glucoside. This extract at concentrations 50 MUM-200 MUM RA
      has cytotoxic activity and initiates cell death through apoptosis. Extracts
      prepared with 70% ethanol contain the biggest amount of active compounds. These
      extracts have the highest cytotoxic activity on glioblastoma cells. They initiate
      generation of intracellular ROS and cell death through apoptosis and necrosis.
      Our data suggest that differently prepared lemon balm extracts differently affect
      glioblastoma cells and can be used as neuroprotective agents in several
      therapeutic strategies.

PMID- 27688826
TI  - Altered Striatocerebellar Metabolism and Systemic Inflammation in Parkinson's
      Disease.
AB  - Parkinson's disease (PD) is the most second common neurodegenerative movement
      disorder. Neuroinflammation due to systemic inflammation and elevated oxidative
      stress is considered a major factor promoting the pathogenesis of PD, but the
      relationship of structural brain imaging parameters to clinical inflammatory
      markers has not been well studied. Our aim was to evaluate the association of
      magnetic resonance spectroscopy (MRS) measures with inflammatory markers. Blood
      samples were collected from 33 patients with newly diagnosed PD and 30 healthy
      volunteers. MRS data including levels of N-acetylaspartate (NAA), creatine (Cre),
      and choline (Cho) were measured in the bilateral basal ganglia and cerebellum.
      Inflammatory markers included plasma nuclear DNA, plasma mitochondrial DNA, and
      apoptotic leukocyte levels. The Cho/Cre ratio in the dominant basal ganglion, the
      dominant basal ganglia to cerebellum ratios of two MRS parameters NAA/Cre and
      Cho/Cre, and levels of nuclear DNA, mitochondrial DNA, and apoptotic leukocytes
      were significantly different between PD patients and normal healthy volunteers.
      Significant positive correlations were noted between MRS measures and
      inflammatory marker levels. In conclusion, patients with PD seem to have abnormal
      levels of inflammatory markers in the peripheral circulation and deficits in MRS
      measures in the dominant basal ganglion and cerebellum.

PMID- 27688827
TI  - Antioxidant and Vasodilator Activity of Ugni molinae Turcz. (Murtilla) and Its
      Modulatory Mechanism in Hypotensive Response.
AB  - Hypertension is a systemic condition with high morbidity and mortality rates
      worldwide, which poses an increased risk for cardiovascular diseases. In this
      study, we demonstrated the antioxidant and vasodilator activity of Ugni molinae
      Turcz. (Murtilla) fruit, a berry native to Chile and proposed models to explain
      its modulatory mechanism in hypotensive response. Murtilla fruits were cultivated
      in a germplasm bank and submitted to chemical and biological analyses. The
      phenolic compounds gallic acid, Catechin, Quercetin-3-beta-D-glucoside,
      Myricetin, Quercetin, and Kaempferol were identified. Murtilla extract did not
      generate toxic effects on human endothelial cells and had significant antioxidant
      activity against ROS production, lipid peroxidation, and superoxide anion
      production. Furthermore, it showed dose-dependent vasodilator activity in aortic
      rings in the presence of endothelium, whose hypotensive mechanism is partially
      mediated by nitric oxide synthase/guanylate cyclase and large-conductance calcium
      dependent potassium channels. Murtilla fruits might potentially have beneficial
      effects on the management of cardiovascular diseases.

PMID- 27688829
TI  - Response to: Comment on "The Impact of Chronic Tobacco Smoking on Retinal and
      Choroidal Thickness in Greek Population".

PMID- 27688832
TI  - Patient-Reported Outcomes in Oncology Drug Labeling in the United States: A
      Framework for Navigating Early Challenges.
AB  - BACKGROUND: Despite an increased use of patient-reported outcomes (PROs) in
      oncology clinical trials, integrating the patient perspective into drug approval
      decisions and documentation has been challenging. OBJECTIVES: To review important
      regulatory and measurement terminology, and to provide oncology outcomes
      researchers and those involved with building oncology programs with tools to plan
      PRO data collection, particularly in relation to drug efficacy claims for drug
      labeling in the United States. DISCUSSION: When contemplating a PRO measurement
      strategy for oncology clinical trials, outcomes researchers are challenged in
      several ways. First, given multiple stakeholders, researchers must communicate
      with their scientific, commercial, and regulatory colleagues using often
      misunderstood terms, such as "label," "claim," "end point," "outcome," and
      "concept." Second, because stakeholders do not always have access to data from
      early-stage clinical trials and do not contribute to the target drug's profile in
      early development, researchers are often unable to address the most important
      question in building a measurement strategy: What do we want to say about our
      drug? To overcome these challenges, researchers can systematically develop an end
      point model to facilitate communication among drug development stakeholders using
      a common language and to link the building blocks of a PRO measurement strategy,
      including claims, concepts, questionnaires, and end points. We developed a model
      that characterizes a disease by its proximal signs and/or symptoms and
      increasingly distal health outcomes to provide researchers potential measurement
      concepts that can be instrumental in selecting PRO questionnaires for use in
      studies. CONCLUSION: PRO data collected in clinical trials should be used in drug
      development to evaluate the drug's efficacy; it is encouraging that US regulators
      are willing to work with drug sponsors to overcome the challenges associated with
      the development, implementation, and interpretation of PROs. The tools discussed
      in this article can facilitate the planning process for oncology researchers, as
      well as assist in communicating with US regulators.

PMID- 27688828
TI  - Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular
      Degeneration.
AB  - Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a
      circadian fashion, but it is produced in many other organs, including the retina,
      which seems to be especially important as the eye is a primary recipient of
      circadian signals. Melatonin displays strong antioxidative properties, which
      predispose it to play a protective role in many human pathologies associated with
      oxidative stress, including premature aging and degenerative disease. Therefore,
      melatonin may play a role in age-related macular degeneration (AMD), a disease
      affecting photoreceptors, and retinal pigment epithelium (RPE) with an
      established role of oxidative stress in its pathogenesis. Several studies have
      shown that melatonin could exert the protective effect against damage to RPE
      cells evoked by reactive oxygen species (ROS), but it has also been reported to
      increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like
      synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria
      at relatively high levels; thus, melatonin may prevent mitochondrial damage in
      AMD. The retina contains telomerase, an enzyme implicated in maintaining the
      length of telomeres, and oxidative stress inhibits telomere synthesis, while
      melatonin overcomes this effect. These features support considering melatonin as
      a preventive and therapeutic agent in the treatment of AMD.

PMID- 27688833
TI  - Economic Burden of Toxicities Associated with Treating Metastatic Melanoma in the
      United States.
AB  - BACKGROUND: Little has been reported on the costs of managing the adverse events
      (AEs) associated with current therapies for patients with regional or distant
      metastatic melanoma. OBJECTIVES: To identify treatment-related AEs in patients
      with metastatic melanoma and to estimate the associated costs of treating these
      AEs in the United States. METHODS: A cost-estimation study for AEs associated
      with treatment of metastatic melanoma was conducted from 2012 to 2013 by
      identifying grades 3 and 4 AEs through the use of a comprehensive search of drug
      labels and English-language, published phase 2/3 studies in PubMed, conference
      abstracts, and the National Comprehensive Cancer Network guidelines. Resource
      utilization for the management of each type of AE in the outpatient setting was
      obtained via interviews with 5 melanoma specialists in the United States. Unit
      costs for an AE associated with melanoma treatment in the outpatient setting were
      assigned using Medicare reimbursement rates to obtain these costs.
      Hospitalization and length-of-stay costs were estimated for each associated AE
      using the large national claims database Optum Clinformatics Data Mart for the
      period of July 1, 2004, to November 30, 2012. RESULTS: The most common AEs
      associated with chemotherapies used for melanoma were neutropenia, vomiting, and
      anemia. The most common AEs associated with vemurafenib were cutaneous squamous
      cell carcinoma or keratoacanthoma, rash, and elevated liver enzymes; the most
      common AEs associated with dabrafenib were cutaneous squamous-cell carcinoma and
      pyrexia. Trametinib was most often associated with hypertension and rash. The
      most common AEs with ipilimumab were immune-related diarrhea or colitis, dyspnea,
      anemia, vomiting, and, less frequently, hypophysitis. The most common grade 3/4
      AE with talimogene laherparepvec was cellulitis. The highest treatment costs for
      an AE in the outpatient setting were for neutropenia ($2092), headache ($609),
      and peripheral neuropathy ($539). The highest mean inpatient costs for an AE were
      for acute myocardial infarction, sepsis, and coma, which ranged from $31,682 to
      $47,069. Colitis or diarrhea, cutaneous squamous-cell carcinoma,
      thrombocytopenia, hyponatremia, oliguria or anuria, hypertension, anemia, and
      elevated liver enzymes were associated with mean costs for hospitalization
      ranging from $19,122 to $26,861. CONCLUSION: The costs of managing treatment
      related AEs in patients with metastatic melanoma are substantial. Effective
      treatments with improved safety profiles may help to reduce these costs. Until
      real-world evidence for the costs associated with treatment toxicity is available
      in the outpatient and inpatient settings, the costs estimated in this study can
      help inform decision makers about the cost-effectiveness of managing patients
      with metastatic melanoma.

PMID- 27688835
TI  - Innovation Tops Current Trends in the 2016 Oncology Drug Pipeline.

PMID- 27688834
TI  - Thromboembolic Events Associated with Bevacizumab plus Chemotherapy for Patients
      with Colorectal Cancer: A Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Bevacizumab is a recombinant, humanized monoclonal antibody that
      hinders the proliferation of new blood vessels required for malignant
      progression. The drug is considered safe and tolerable; however, some controversy
      remains about whether it is linked to venous and arterial thromboembolic events
      (TEEs). OBJECTIVE: To evaluate the risk for overall, venous, and arterial TEEs in
      patients with colorectal cancer (CRC) who are administered bevacizumab plus
      chemotherapy in randomized controlled trials (RCTs). METHODS: We searched PubMed
      and CENTRAL databases to extract reports of relevant trials that were published
      in English between January 1, 2003, and December 31, 2014. All RCTs in which
      bevacizumab plus chemotherapy was compared with standard chemotherapy or with
      placebo plus chemotherapy for the treatment of CRC, and TEEs were reported, were
      included in a meta-analysis. Risk ratios (RRs) with 95% confidence intervals
      (CIs) of TEEs were calculated for each RCT. Because the between-study
      heterogeneities (I2) were insignificant, a fixed-effect model was used to
      determine the effect size of each TEE. A funnel plot was created to assess
      publication bias, and 2 forms of sensitivity analyses were performed for each
      outcome. RESULTS: This meta-analysis included 22 RCTs with a total of 13,185
      patients. Overall, compared with the control groups, patients with CRC who
      received bevacizumab were at significant risk for overall TEEs (RR, 1.334; 95%
      CI, 1.191-1.494; P <.001; I2 = 1.37%). Regarding venous TEEs, a significant risk
      was observed for patients who received bevacizumab versus control patients (RR,
      1.244; 95% CI, 1.091-1.415; P = .001; I2 = 0.0%). Similarly, the risk for
      arterial TEEs was significant in bevacizumab-treated patients (RR, 1.627; 95% CI,
      1.162-2.279; P = .005; I2 = 0.0%). Sensitivity analyses did not affect the level
      of significance of the effect size for each outcome, and no significant
      publication bias was observed. CONCLUSION: In all the studies reviewed in this
      meta-analysis, the risk for venous or arterial TEEs was associated with
      bevacizumab use in patients with CRC. Healthcare providers are encouraged to
      consider thromboprophylaxis agents, periodically monitor their patients who
      receive bevacizumab, and carefully manage patients who are at increased risk for
      those complications.

PMID- 27688837
TI  - The First Study of Cartilage by Magnetic Resonance: A Historical Account.
AB  - OBJECTIVE: To recap the historical journey leading to the first cartilage
      research article using nuclear magnetic resonance (NMR), published in 1955 by 2
      Swedish researchers, Erik Odeblad and Gunnar Lindstrom. DESIGN: Extensive
      Internet search utilizing both English and Swedish websites, and reading the
      dissertations available at the Royal Institute of Technology (Stockholm, Sweden)
      and via interlibrary loans at Oakland University (Michigan, USA). RESULTS: Using
      a primitive NMR instrument that Lindstrom built for his graduate research at the
      Nobel Institute for Physics (Stockholm, Sweden), Odeblad and Lindstrom studied
      the characteristics of the NMR signal in calf cartilage. The authors wrote, "In
      cartilage and fibrous tissue, in which the proton signals probably arise from
      highly viscous water with short spin-lattice relaxation time, the signals were
      also larger than would correspond to the water content." The authors speculated
      the signal differences between water and biological tissues could be attributed
      to the absorption and organization of the water molecules to the proteins in the
      tissue, which was remarkably accurate. CONCLUSIONS: It is quite certain that
      Odeblad and Lindstrom published the first biomedical study using NMR in 1955. In
      this article, cartilage and a number of other biological tissues were examined
      for the first time using NMR.

PMID- 27688836
TI  - Whole genome shotgun sequence of Bacillus amyloliquefaciens TF28, a biocontrol
      entophytic bacterium.
AB  - Bacillus amyloliquefaciens TF28 is a biocontrol endophytic bacterium that is
      capable of inhibition of a broad range of plant pathogenic fungi. The strain has
      the potential to be developed into a biocontrol agent for use in agriculture.
      Here we report the whole-genome shotgun sequence of the strain. The genome size
      of B. amyloliquefaciens TF28 is 3,987,635 bp which consists of 3754 protein
      coding genes, 65 tandem repeat sequences, 47 minisatellite DNA, 2 microsatellite
      DNA, 63 tRNA, 7rRNA, 6 sRNA, 3 prophage and CRISPR domains. 

PMID- 27688839
TI  - Matrix-Associated Autologous Chondrocyte Implantation: A Clinical Follow-Up at 15
      Years.
AB  - INTRODUCTION: A prospective clinical investigation was carried out in order to
      clarify whether Matrix-associated autologous chondrocyte implantation (MACI)
      results in clinical improvement at long-term follow-up. HYPOTHESIS: MACI will
      result in clinical improvement at long-term follow-up. STUDY DESIGN: Case series;
      level of evidence, 4. METHODS: Thirty-eight patients were treated with MACI.
      These patients were evaluated for up to a mean of 16 years (range 15-17 years)
      after the intervention. Three different scores (Lysholm-Gilquist score,
      International Cartilage Repair Society score, and Tegner score) formed the basis
      of this study. Overall, we were able to obtain valid preoperative and
      postoperative results from 18 (47%) of 38 patients. In 1 patient, both knees were
      treated. In 4 patients, an arthroplasty was implanted over the course of time;
      thus they were excluded from this case series. In conclusion, follow-up of 15
      knees was performed in the recent series. RESULTS: In subjective rating, 12 out
      of 14 patients (86%) rated the function of their knee as much better or better
      than before the index procedure. All numerical outcome scores showed significant
      improvement compared to the preoperative value (preoperative/postoperative at 5
      years/postoperative at 15 years): Lysholm score 59.6 (+/-24.6)/78.6 (+/
      21.5)/82.7 (+/-11.3), International Knee Documentation Committee score 50.6 (+/
      22.7)/64.7 (+/-21.6)/69.7 (+/-18.7), Tegner score 3.0 (+/-2.2)/3.6 (+/-1.5)/5.2
      (+/-1.7). CONCLUSION: The significantly improved results on 3 scores after 15
      years suggest that MACI represents a suitable treatment of local cartilage
      defects in the knee.

PMID- 27688838
TI  - Long-Term Outcomes after Autologous Chondrocyte Implantation: A Systematic Review
      at Mean Follow-Up of 11.4 Years.
AB  - OBJECTIVE: Autologous chondrocyte implantation (ACI) has not been proven to be
      durable over the long-term. The purpose of this systematic review was (1) to
      evaluate activity level and knee function, (2) to evaluate reoperation and
      failure rates, and (3) to analyze risk factors for reoperation and failure of ACI
      at minimum long-term follow-up. DESIGN: A comprehensive review was performed for
      studies with long-term outcomes after ACI for cartilage defect repair. Studies
      reported outcome scores such as Tegner score, Lysholm score, and International
      Knee Documentation Society (IKDC) score along with rates of failure and
      reoperation. Modified Coleman Methodology Scores were calculated to assess study
      methodological quality. RESULTS: Nine studies with a total of 771 patients with a
      mean age of 33.4 +/- 2.5 years, mean defect size of 5.9 +/- 1.6 cm(2), and mean
      follow-up of 11.4 years were included. Tegner score, Lysholm score, and IKDC
      score change from preoperative to final follow-up was 1.1 (95% CI 0.8-1.4, P <
      0.001), 24.9 points (95% CI 18.8-31, P < 0.001), and 16.5 points (95% CI 5.4
      27.5, P < 0.01), respectively. The mean failure and reoperation rates were 18%
      and 37%, respectively. Increased age and lesion size (>4.5 cm(2)) were
      significantly correlated with increased risk of reoperation and failure.
      CONCLUSIONS: Overall, ACI demonstrated successful outcomes in 82% of patients
      over the long-term. Increased patient age and lesion size greater than 4.5 cm(2)
      were risk factors for a higher reoperation and failure rate. Nonetheless, this
      review is limited by heterogeneity in surgical technique, and lesion and patient
      characteristics.

PMID- 27688840
TI  - Acute Delamination of Commercially Available Decellularized Osteochondral
      Allograft Plugs: A Report of Two Cases.
AB  - Articular cartilage injuries, and corresponding surgical procedures, are
      occurring with increasing frequency as identified by a review of recent surgical
      trends. Concerns have grown in recent years regarding the longevity of results
      following microfracture, with a shift toward cartilage restoration procedures in
      recent years. This case report describes 2 cases of acute failure following the
      use of commercially available osteochondral allograft plugs used for the
      treatment of osteochondral defects of the distal femur. In both cases the
      chondral surface of the plug delaminated from the underlying cancellous bone,
      resulting in persistent pain and swelling requiring reoperation and removal of
      the loose fragments. Caution should be employed when considering use of these
      plugs for the treatment of osteochondral lesions, as similar outcomes have not
      been noted with other cartilage restoration techniques. 

PMID- 27688841
TI  - Safety of Repeated Injections of Sodium Hyaluronate (SUPARTZ) for Knee
      Osteoarthritis: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: Though there is no consensus on its efficacy, knee osteoarthritis is
      symptomatically managed with intra-articular hyaluronic acid (IAHA). Recent
      reports suggest that IAHA may delay the need for total knee replacement, with the
      magnitude of delay proportional to the number of injection series. However, the
      safety of repeated injection series is reported to vary between commercial
      products. This report describes a systematic review of safety data on repeated
      treatment courses of SUPARTZ. DESIGN: We performed a systematic search of
      MEDLINE, Cochrane database, EMBASE, Web of Science, Google Scholar, and
      unpublished data. We included all human randomized controlled trials or
      observational studies with adverse event (AE) data for SUPARTZ in knee
      osteoarthritis. Two independent reviewers extracted data and evaluated study
      quality. Data were analyzed separately for the first and subsequent series of
      injections. RESULTS: The primary sources for repeated-injection data on SUPARTZ
      were a postmarket registry (N = 7404), 4 prospective studies (N = 127 total), and
      a retrospective study (N = 220). None of the sources reported increased frequency
      or severity of AEs with repeated injections. In the registry, 95% of multiple
      injection-series patients who reported an AE did so during the first series. None
      of the AEs was serious, and most resolved spontaneously without medical
      intervention. The overall adverse event rate after repeat courses of SUPARTZ was
      0.008 (95% confidence interval: 0.001-0.055). CONCLUSIONS: Multiple courses of
      SUPARTZ injections appear to be at least as safe, and probably safer, than the
      first course. This study supports the safety of repeat courses of SUPARTZ
      injections for knee osteoarthritis.

PMID- 27688842
TI  - Expression of TGF-beta Signaling Regulator RBPMS (RNA-Binding Protein With
      Multiple Splicing) Is Regulated by IL-1beta and TGF-beta Superfamily Members, and
      Decreased in Aged and Osteoarthritic Cartilage.
AB  - OBJECTIVE: RNA-binding protein with multiple splicing (RBPMS) has been shown to
      physically interact with Smads and enhance transforming growth factor-beta (TGF
      beta)-mediated Smad2/3 transcriptional activity in mammalian cells. Objective of
      this study was to examine whether expression of RBPMS is regulated by interleukin
      1beta (IL)-1beta and TGF-beta superfamily growth factors and whether expression
      of RBPMS is altered during aging and experimental osteoarthritis. METHODS:
      Expression of RBPMS protein was investigated in chondrocyte cell lines of murine
      (H4) and human (G6) origin using Western blot analysis. Regulation of RBPMS
      expression in H4 chondrocytes at mRNA level was done by reverse transcriptase
      quantitative polymerase chain reaction. Furthermore, characterization of Smad
      signaling pathways regulating RBPMS expression was performed by blocking studies
      using small molecule inhibitors or by transfection studies with adenoviral vector
      constructs (constitutive-active ALK1 and constitutive-active ALK5). Expression of
      RBPMS in cartilage of different age groups of C57BL/6N mice (6 months and 20
      months) and in a surgically induced osteoarthritis (OA) mouse model was analyzed
      using immunohistochemistry. RESULTS: RBPMS was shown to be expressed in
      chondrocytes and cartilage of murine, human, and bovine origin. TGF-beta
      inhibited RBPMS expression while BMP2 and IL-1beta increased its expression. TGF
      beta-induced inhibition was blocked by ALK5 inhibitor. Overexpression of ca-ALK1
      stimulated RBPMS expression. Moreover, RBPMS expression was found to be reduced
      with ageing and in OA pathogenesis. CONCLUSIONS: Expression of RBPMS in
      chondrocytes is regulated by TGF-beta superfamily members and IL-1beta,
      indicating a counter-regulatory mechanism. Expression of RBPMS, in cartilage and
      its reduction during ageing and OA might suggest its potential role in the
      maintenance of normal articular cartilage.

PMID- 27688843
TI  - Bilayer Implants: Electromechanical Assessment of Regenerated Articular Cartilage
      in a Sheep Model.
AB  - OBJECTIVE: To compare the regenerative capacity of 2 distinct bilayer implants
      for the restoration of osteochondral defects in a preliminary sheep model.
      METHODS: Critical sized osteochondral defects were treated with a novel
      biomimetic poly-epsilon-caprolactone (PCL) implant (Treatment No. 2; n = 6) or a
      combination of Chondro-Gide and Orthoss (Treatment No. 1; n = 6). At 19 months
      postoperation, repair tissue (n = 5 each) was analyzed for histology and
      biochemistry. Electromechanical mappings (Arthro-BST) were performed ex vivo.
      RESULTS: Histological scores, electromechanical quantitative parameter values,
      dsDNA and sGAG contents measured at the repair sites were statistically lower
      than those obtained from the contralateral surfaces. Electromechanical mappings
      and higher dsDNA and sGAG/weight levels indicated better regeneration for
      Treatment No. 1. However, these differences were not significant. For both
      treatments, Arthro-BST revealed early signs of degeneration of the cartilage
      surrounding the repair site. The International Cartilage Repair Society II
      histological scores of the repair tissue were significantly higher for Treatment
      No. 1 (10.3 +/- 0.38 SE) compared to Treatment No. 2 (8.7 +/- 0.45 SE). The
      parameters cell morphology and vascularization scored highest whereas tidemark
      formation scored the lowest. CONCLUSION: There was cell infiltration and
      regeneration of bone and cartilage. However, repair was incomplete and
      fibrocartilaginous. There were no significant differences in the quality of
      regeneration between the treatments except in some histological scoring
      categories. The results from Arthro-BST measurements were comparable to
      traditional invasive/destructive methods of measuring quality of cartilage
      repair.

PMID- 27688844
TI  - Transplantation of Scaffold-Free Cartilage-Like Cell-Sheets Made from Human Bone
      Marrow Mesenchymal Stem Cells for Cartilage Repair: A Preclinical Study.
AB  - OBJECTIVE: The object of this study was to determine culture conditions that
      create stable scaffold-free cartilage-like cell-sheets from human bone marrow
      derived mesenchymal stem cells (hBMSCs) and to assess their effects after
      transplantation into osteochondral defects in nude rats. DESIGN: (Experiment 1)
      The hBMSCs were harvested from 3 males, the proliferative and chondrogenic
      capacities were assessed at passage 1, and the cells were expanded in 3 different
      culture conditions: (1) 5% fetal bovine serum (FBS), (2) 10% FBS, and (3) 5% FBS
      with fibroblast growth factor 2 (FGF-2). The cells were harvested and made
      chondrogenic pellet culture. The cell proliferation rate, glycosaminoglycan/DNA
      ratio, and safranin-O staining intensity of pellets cultured condition 3 were
      higher than those of conditions 1 and 2. (Experiment 2) The hBMSCs were expanded
      and passaged 3 times under culture condition 3, and fabricate the cell-sheets in
      chondrogenic medium either with or without FBS. The cell-sheets fabricated with
      FBS maintained their size with flat edges. (Experiment 3) The cell-sheets were
      transplanted into osteochondral defects in nude rats. Histological analysis was
      performed at 2, 4, and 12 weeks after surgery. RESULTS: The osteochondral repair
      was better after sheet transplantation than in the control group and
      significantly improved Wakitani score. Immunostaining with human-specific
      vimentin antibody showed that the transplanted cells became fewer and disappeared
      at 12 weeks. CONCLUSIONS: These results indicate that culture with FGF-2 may help
      to quickly generate sufficient numbers of cells to create stable and reliable
      scaffold-free cartilage-like cell-sheets, which contribute to the regeneration of
      osteochondral defects.

PMID- 27688847
TI  - Counting with Colours? Effect of Colours on the Numerical Abilities of House
      Crows (Corvus splendens) and Common Myna (Acridotheres tristis).
AB  - We conducted several aviary experiments to investigate the influence of colours
      in quantity judgments of two species of birds; house crow (Corvus splendens) and
      common myna (Acridotheres tristis). Different quantity (in seven different food
      proportions) of mealworms were presented nonsequentially to all birds using
      artificially coloured red mealworms, for experiment 1, and using artificially
      coloured green mealworms, for experiment 2. Both red and green coloured mealworms
      have no significant effect on house crow's quantity judgments (red: ANOVA: F6,30
      = 1.748, p = 0.144; and green: ANOVA: F6,30= 1.085, p = 0.394). Common myna,
      however, showed a strong influence of red colour in their quantity judgment (
      ANOVA: F6,30 = 2.922, p = 0.023) as they succeeded in choosing the largest amount
      of food between two cups, but not when offered food using green coloured
      mealworms ( ANOVA: F6,30 = 1.183, p = 0.342). In the next experiment, we
      hypothesised that both house crow and common myna will prefer red coloured food
      items over green coloured food items, when factors such as the amount of food is
      equal. We chose to test red and green colours because both colours play an
      important role in most avian food selections. Results showed that there were no
      significant differences in the selection of red or green coloured mealworms for
      both house crows ( ANOVA: F6,30 = 2.310, p = 0.06) and common myna ( ANOVA: F6,30
      = 0.823, p = 0.561).

PMID- 27688846
TI  - Modulation of Superficial Zone Protein/Lubricin/PRG4 by Kartogenin and
      Transforming Growth Factor-beta1 in Surface Zone Chondrocytes in Bovine Articular
      Cartilage.
AB  - OBJECTIVE: Superficial zone protein (SZP)/lubricin/PRG4 functions as a boundary
      lubricant in articular cartilage to decrease friction and wear. As articular
      cartilage lubrication is critical for normal joint function, the accumulation of
      SZP at the surface of cartilage is important for joint homeostasis. Recently, a
      heterocyclic compound called kartogenin (KGN) was found to induce chondrogenic
      differentiation and enhance mRNA expression of lubricin. The objective of this
      study was to determine whether KGN can stimulate synthesis of SZP in superficial
      zone, articular chondrocytes. DESIGN: We investigated the effects of KGN and
      transforming growth factor-beta1 (TGF-beta1) on articular cartilage and synovium
      of the bovine knee joint by evaluating SZP secretion by enzyme-linked
      immunosorbent assay analysis. Monolayer, micromass, and explant cultures of
      articular cartilage, and monolayer culture of synoviocytes, were treated with
      KGN. SZP accumulation in the medium was evaluated and mRNA expression was
      measured through quantitative polymerase chain reaction. RESULTS: TGF-beta1
      stimulated SZP secretion by superficial zone chondrocytes in monolayer, explant,
      and micromass cultures as expected. In addition, SZP secretion was inhibited by
      IL-1beta in explant cultures, and enhanced by TGF-beta1 in synoviocyte monolayer
      cultures. Although KGN elicited a 1.2-fold increase in SZP mRNA expression in
      combination with TGF-beta1, KGN neither stimulated any significant increases in
      SZP synthesis nor prevented catabolic decreases in SZP production from IL-1beta.
      CONCLUSIONS: These data suggest that the chondrogenic effects of KGN depend on
      cellular phenotype and differentiation status, as KGN did not alter SZP synthesis
      in differentiated, superficial zone articular chondrocytes.

PMID- 27688845
TI  - The Chondroprotective Role of Erythromycin in a Murine Joint Destruction Model.
AB  - OBJECTIVE: Inflammation is a major player in the joint destruction process.
      Macrolide antibiotics have recently been found to have a novel anti-inflammatory
      function, but their effects on the joint are unknown. Our objective was to
      investigate the effect of macrolide antibiotic erythromycin on cartilage gene
      expression under inflammatory conditions as well as on joint pathology in an in
      vivo inflammatory joint destruction model. DESIGN: In our in vivo studies, mouse
      knee joints were injected with monosodium iodoacetate (MIA), a chemical that
      inhibits glycolysis and causes joint inflammation and matrix loss. Erythromycin
      was administered by daily intraperitoneal injection. Changes in joint cartilage
      and synovium were evaluated by histological analysis. In our in vitro studies,
      primary bovine articular chondrocytes were treated with erythromycin in the
      presence of pro-inflammatory cytokine IL-1beta or lipopolysaccharide (LPS), and
      cartilage gene expression analysis was performed. RESULTS: Regional differences
      in cartilage matrix destruction along the medial-lateral axis were observed in
      joints of MIA-injected mice. Erythromycin treatment inhibited cartilage matrix
      loss and synovitis in these joints. In addition, erythromycin inhibited IL-1beta
      and LPS-induced expression of MMPs and iNOS, as well as the positive regulatory
      loop between IL-1beta and Toll-like receptor 4 (TLR4) in articular chondrocytes.
      Furthermore, erythromycin prevented LPS-induced NF-kappaB activation, a key
      mediator of TLR4-mediated cartilage destruction process. CONCLUSIONS:
      Erythromycin has the ability to inhibit catabolic gene expression mediated by IL
      1beta and TLR4 in chondrocytes in vitro and maintains cartilage matrix levels in
      experimental inflammatory joint destruction in vivo, suggesting that it possesses
      a chondroprotective activity.

PMID- 27688848
TI  - Current Status of the Milky Stork Re-introduction Programme in Malaysia and Its
      Challenges.
AB  - This review discussed the current status of the Milky Stork Re-introduction
      Programme in Malaysia and the challenges it faced. Although it has continued for
      almost seven years, more challenges appeared as time elapsed mainly due to the
      arising conflicts between the implementation of conservation policy versus the
      development projects in Kuala Gula. Hence, the released population is struggling
      to adapt mainly due to the reduction of suitable habitat for nesting and
      disturbed foraging areas by the continuous anthropogenic activities. Furthermore,
      the lack of appropriate training among captive storks prior to being released
      also slows the adaptation of the birds in their new habitat. The increasing
      pattern of pollution in the area is also highlighted. Several suggestions were
      given to help improve the current re-introduction programme. These include
      improvements to the captive training method, improvement of the existing
      enclosure's condition and environment, protection of remaining mangrove forest,
      creation of a buffer zone to mitigate the increasing pollution level in the area,
      close monitoring of the released population, and maintaining continuous support
      and awareness among the public. Considering the ongoing anthropogenic activities
      that may impair the status of Kuala Gula as an important bird sanctuary, emphasis
      should be given to achieve sustainable development throughout the area. 

PMID- 27688849
TI  - Toxicity of Chlorophyllin against Lymnaea acuminata at Different Wavelengths of
      Visible Light.
AB  - Fasciolosis is a water and food-borne disease caused by the liver fluke Fasciola
      hepatica and Fasciola gigantica. This disease is widespread in different parts of
      the world. Lymnaeidae and Planorbidae snails are the intermediate hosts of these
      flukes. Snail population management is a good tool to control fasciolosis because
      gastropods represent the weakest link in the life-cycle of trematodes.
      Chlorophyll can be extracted from any green plant. Chlorophyllin was prepared
      from spinach in 100% ethanol by using different types of chemicals. The
      chlorophyll obtained from spinach was transformed into water-soluble
      chlorophyllin. In the present paper, toxicity of chlorophyllin against the snail
      Lymnaea acuminata was time and concentration dependent. The toxicity of extracted
      and pure chlorophyllin at continuous 4 h exposure of sunlight was highest with
      lethal concentration (LC50) of 331.01 mg/L and 2.60 mg/L, respectively, than
      discontinuous exposure of sunlight up to 8 h with LC50 of 357.04 mg/L and 4.94
      mg/L, respectively. Toxicity of extracted chlorophyllin was noted in the presence
      of different monochromatic visible lights. The highest toxicity was noted in
      yellow light (96 h, LC50 392.77 mg/L) and the lowest in green light (96 h, LC50
      833.02 mg/L). Chlorophyllin in combination with solar radiation or different
      wavelength of monochromatic visible lights may become a latent remedy against the
      snail L. acuminata. It was demonstrated that chlorophyllin was more toxic in
      sunlight. Chlorophyllin is ecologically safe and more economical than synthetic
      molluscicides which have the potential to control the incidence of fasciolosis in
      developing countries. 

PMID- 27688850
TI  - Cellular Biochemical Changes in Selaginella tamariscina (Beauv.) Spring and
      Sellaginella plana (Desv. ex Poir.) Heiron. as Induced by Desiccation.
AB  - The biochemical changes in two Selaginella species namely, S. tamariscina
      (Beauv.) Spring and S. plana (Desv. ex Poir.) Heiron., as induced by desiccation
      and subsequent rehydration were explored. Plants were allowed to dehydrate
      naturally by withholding irrigation until shoot's relative water content (RWC)
      reached <10%. After which, dehydrated plants were watered until fully rehydrated
      states were obtained which was about 90% RWC or more. Desiccation-tolerance
      characteristics were observed in S. tamariscina while desiccation-sensitivity
      features were seen in S. plana. Membrane integrity was maintained in S.
      tamariscina but not in S. plana as evidenced in the relative electrolyte leakage
      measurements during desiccation phase and the subsequent rehydration stage.
      Pigment analyses revealed conservation of some chlorophylls and carotenoids
      during desiccation and reaching control levels following rehydration in S.
      tamariscina. Very low pigment contents were found in S. plana during desiccation
      phase and the pigments were not recovered during rehydration attempt. Meanwhile,
      compatible solute determination showed rise in total sugar and proline contents
      of desiccated S. tamariscina only, indicating presence of biochemical protection
      machineries in this species and absence of such in S. plana during dehydrating
      conditions. These data indicate that one key element for desiccation-tolerance in
      lower vascular plants is the ability to protect tissues from severe damages
      caused by intense desiccation. 

PMID- 27688851
TI  - Anti-malarial Activities of Two Soil Actinomycete Isolates from Sabah via
      Inhibition of Glycogen Synthase Kinase 3beta.
AB  - Exploiting natural resources for bioactive compounds is an attractive drug
      discovery strategy in search for new anti-malarial drugs with novel modes of
      action. Initial screening efforts in our laboratory revealed two preparations of
      soil-derived actinomycetes (H11809 and FH025) with potent anti-malarial
      activities. Both crude extracts showed glycogen synthase kinase 3beta (GSK3beta)
      inhibitory activities in a yeast-based kinase assay. We have previously shown
      that the GSK3 inhibitor, lithium chloride (LiCl), was able to suppress
      parasitaemia development in a rodent model of malarial infection. The present
      study aims to evaluate whether anti-malarial activities of H11809 and FH025
      involve the inhibition of GSK3beta. The acetone crude extracts of H11809 and
      FH025 each exerted strong inhibition on the growth of Plasmodium falciparum 3D7
      in vitro with 50% inhibitory concentration (IC50) values of 0.57 +/- 0.09 and
      1.28 +/- 0.11 ug/mL, respectively. The tested extracts exhibited Selectivity
      Index (SI) values exceeding 10 for the 3D7 strain. Both H11809 and FH025 showed
      dosage-dependent chemo-suppressive activities in vivo and improved animal
      survivability compared to non-treated infected mice. Western analysis revealed
      increased phosphorylation of serine (Ser 9) GSK3beta (by 6.79 to 6.83-fold) in
      liver samples from infected mice treated with H11809 or FH025 compared to samples
      from non-infected or non-treated infected mice. A compound already identified in
      H11809 (data not shown), dibutyl phthalate (DBP) showed active anti-plasmodial
      activity against 3D7 (IC50 4.87 +/- 1.26 ug/mL which is equivalent to 17.50 uM)
      and good chemo-suppressive activity in vivo (60.80% chemo-suppression at 300
      mg/kg body weight [bw] dosage). DBP administration also resulted in increased
      phosphorylation of Ser 9 GSK3beta compared to controls. Findings from the present
      study demonstrate that the potent anti-malarial activities of H11809 and FH025
      were mediated via inhibition of host GSK3beta. In addition, our study suggests
      that DBP is in part the bioactive component contributing to the anti-malarial
      activity displayed by H11809 acting through the inhibition of GSK3beta. 

PMID- 27688852
TI  - Beneficial Properties of Probiotics.
AB  - Probiotics are live microorganisms that can be found in fermented foods and
      cultured milk, and are widely used for the preparation of infant food. They are
      well-known as "health friendly bacteria", which exhibit various health beneficial
      properties such as prevention of bowel diseases, improving the immune system, for
      lactose intolerance and intestinal microbial balance, exhibiting
      antihypercholesterolemic and antihypertensive effects, alleviation of
      postmenopausal disorders, and reducing traveller's diarrhoea. Recent studies have
      also been focused on their uses in treating skin and oral diseases. In addition
      to that, modulation of the gut-brain by probiotics has been suggested as a novel
      therapeutic solution for anxiety and depression. Thus, this review discusses on
      the current probiotics-based products in Malaysia, criteria for selection of
      probiotics, and evidences obtained from past studies on how probiotics have been
      used in preventing intestinal disorders via improving the immune system, acting
      as an antihypercholesterolemic factor, improving oral and dermal health, and
      performing as anti-anxiety and anti-depressive agents. 

PMID- 27688853
TI  - Colour Cues: Effects of Ipomoea Plant Extract on Culex quinquefasciatus Say
      Gravid Females in Choosing Oviposition Site.
AB  - The interaction between plants and insects is dynamic, and may favour either the
      plant or the insect. Plant chemicals are deeply implicated in this relationship
      and influence insect behaviour. Here, we investigated the oviposition behaviour
      response of Culex quinquefasciatus mosquitoes based on the colour cues produced
      by Ipomoea cairica leaves extract. In this study, two sets of oviposition choice
      experiments were conducted: (1) single solution in a cage; and (2) multiple
      concentration solutions in a cage. In the single solution experiment, only 1
      available oviposition site was offered to 5 gravid females and in the multiple
      concentration tests, 4 available oviposition sites were offered to 20 gravid
      females. The tested concentrations were set up at 100 mL of: (1) control
      (distilled water only); (2) 50 ppm; (3) 150 ppm; and (4) 300 ppm of I. cairica
      plant extracts. The highest concentration of 300 ppm appeared to show the highest
      intensity with the darkest colour followed by 150 ppm and 50 ppm concentrations.
      More gravid females were found drowned in the highest concentration, 300 ppm of
      acethonilic leaves extract, compared to 150 ppm and 50 ppm of the tested extract.
      No eggs were found in all tested solutions. The studied extract was found to
      effectively attract gravid Cx. quinquefasciatus females and subsequently cause
      mortality and inhibit egg deposition. The interference caused by the acethonilic
      extract of I. cairica on the oviposition activity of Cx. quinquefasciatus can
      result in better control of the vector insect. 

PMID- 27688854
TI  - Five New Records of Terrestrial and Lithophytic Orchids (Orchidaceae) from Penang
      Hill, Malaysia.
AB  - Five new records of terrestrial and lithophytic orchid species were gathered from
      Penang Hill, Pulau Pinang, Malaysia namely Bulbophyllum depressum, Goodyera
      pusilla, Peristylus monticola, Podochilus microphyllus, and Zeuxine gracilis.
      Checklist of each species is provided and their distribution in Penang Hill is
      discussed. 

PMID- 27688855
TI  - Dietary Prebiotics and Probiotics Influence the Growth Performance, Feed
      Utilisation, and Body Indices of Snakehead (Channa striata) Fingerlings.
AB  - This study used a two-phase feeding trial to determine the influence of selected
      dietary prebiotics and probiotics on growth performance, feed utilisation, and
      morphological changes in snakehead (Channa striata) fingerlings as well as the
      duration of these effects over a post-experimental period without
      supplementation. Triplicate groups of fish (22.46 +/-0.17 g) were raised on six
      different treatment diets: three prebiotics (0.2% beta-glucan, 1% galacto
      oligosaccharides [GOS], 0.5% mannan-oligosaccharides [MOS]), two probiotics (1%
      live yeast [Saccharomyces cerevisiae] and 0.01% Lactobacillus acidophilus [LBA]
      powder) and a control (unsupplemented) diet; there were three replicates for each
      treatment. All diets contained 40% crude protein and 12% crude lipid. Fish were
      fed to satiation three times daily. No mortalities were recorded during Phase 1;
      however, 14% mortality was documented in the control and prebiotic-amended fish
      during Phase 2. At the end of Phase 1, growth performance and feed utilisation
      were significantly higher (p<0.05) in the LBA-treated fish, followed by live
      yeast treatment, compared with all other diets tested. The performance of fish on
      the three prebiotic diets were not significantly different from one another but
      was significantly higher than the control diet. During Phase 2 (the post-feeding
      phase), fish growth continued until the 6th week for the probiotic-based diets
      but levelled off after four weeks for the fish fed the prebiotic diets. The feed
      conversion ratio (FCR) was higher in all treatments during the post-feeding
      period. The hepatosomatic index (HSI) did not differ significantly among the
      tested diets. The visceral somatic index (VSI) and intraperitoneal fat (IPF) were
      highest in the LBA-based diet and the control diet, respectively. The body
      indices were significantly different (p<0.05) between Phases 1 and 2. This study
      demonstrates that probiotic-based diets have a more positive influence on the
      growth, feed utilisation, and survival of C. striata fingerlings compared with
      supplementation with prebiotics. 

PMID- 27688856
TI  - Usage of Nest Materials by House Sparrow (Passer domesticus) Along an Urban to
      Rural Gradient in Coimbatore, India.
AB  - The house sparrow (Passer domesticus) is a widely distributed bird species found
      throughout the world. Being a species which has close association with humans,
      they chiefly nest on man-made structures. Here we describe the materials used by
      the house sparrow for making nests along an urban to rural gradient. For the
      current study, we selected the Coimbatore to Anaikatty road (State Highway-164),
      a 27 km inter-state highway, which traverses along an urban core to rural
      outstretch of Coimbatore. Of the 30 nests observed, 15 nests were from the rural,
      8 were from the suburban, and 7 were from the urban areas. The nests had two
      distinct layers, specifically the structural layer and the inner lining. In the
      current study, we identified 11 plant species, 2 types of animal matter, and 6
      types of anthropogenic matter, including plastic pieces and fine rope. The amount
      of anthropogenic materials in the nest formation varied along the gradients. The
      usage of anthropogenic materials was high in urban areas (p<0.05) whereas it did
      not differ at the sub-urban regions (p>0.05). A gradual decrease in the usage of
      plant matter towards the urban area was noticed (p<0.05). This study explicitly
      documents the links between nest material usage along an urban to rural gradient,
      in a human associated bird. 

PMID- 27688857
TI  - Socioeconomic Disparities in Cancer Screening: Organized versus Opportunistic.

PMID- 27688858
TI  - Is It Possible to Delay or Prevent Age-Related Cognitive Decline?
AB  - Already in the 90s, Khachaturian stated that postponing dementia onset by five
      years would decrease the prevalence of the late onset dementia by 50%. After two
      decades of lack of success in dementia drug discovery and development, and
      knowing that worldwide, currently 36 million patients have been diagnosed with
      Alzheimer's disease, a number that will double by 2030 and triple by 2050, the
      World Health Organization and the Alzheimer's Disease International declared that
      prevention of cognitive decline was a 'public health priority.' Numerous
      longitudinal studies and meta-analyses were conducted to analyze the risk and
      protective factors for dementia. Among the 93 identified risk factors, seven
      major modifiable ones should be considered: low education, sedentary lifestyle,
      midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression.
      Three other important modifiable risk factors should also be added to this list:
      midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney
      disease. After their identification, numerous authors attempted to establish
      dementia risk scores; however, the proposed values were not convincing.
      Identifying the possible interventions, able to either postpone or delay dementia
      has been an important challenge. Observational studies focused on a single life
      style intervention increased the global optimism concerning these possibilities.
      However, a recent extensive literature review of the randomized control trials
      (RCTs) conducted before 2014 yielded negative results. The first results of RCTs
      of multimodal interventions (Finnish Geriatric Intervention Study to Prevent
      Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and
      Prediva) brought more optimism. Lastly, interventions targeting compounds of beta
      amyloid started in 2012 and no results have yet been published. 

PMID- 27688859
TI  - The Relationship between the Blood Level of Persistent Organic Pollutants and
      Common Gastrointestinal Symptoms.
AB  - BACKGROUND: Persistent organic pollutants (POPs) are toxic materials that cannot
      be broken down naturally and that easily accumulate in the body. Although several
      studies have attempted to reveal the effects of POPs on the endocrine and nervous
      system and on cancer, few studies focus on the relationship between low-dose POPs
      and public health. We attempted to find a relationship between the level of POPs
      and common gastrointestinal symptoms, including abdominal discomfort, diarrhea,
      and constipation. METHODS: We recruited 121 subjects who visited Kyungpook
      National University Hospital for a health screening. Plasma concentrations were
      evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls
      and 23 types of organochlorine pesticides. Furthermore, the Korean version of the
      Rome III criteria was used to identify gastrointestinal symptoms. RESULTS: Our
      results showed that abdominal discomfort had an inverse relationship with several
      polychlorinated biphenyls. Moreover, an inverted U-shaped relationship was
      observed between abdominal discomfort and several other organochlorine pesticides
      including p,p'-dichlorodiphenyldichloroethane and p,p'
      dichlorodiphenyltrichloroethane, and the effects of these pesticides on abdominal
      discomfort were similar to that of organochlorine pesticides on obesity and
      metabolic syndrome. CONCLUSION: Our results suggest that mild and unspecified
      gastrointestinal symptoms with no clear cause could be related to POPs levels.

PMID- 27688860
TI  - Relationship between Blood Mercury Concentration and Bone Mineral Density in
      Korean Men in the 2008-2010 Korean National Health and Nutrition Examination
      Survey.
AB  - BACKGROUND: The results of previous studies on the association between blood
      mercury (Hg) and bone mineral density (BMD) are inconsistent. We therefore used a
      large-scale nationwide representative sample of Korean men to investigate the
      relationship between these two parameters. METHODS: A nationwide cross-sectional
      study was conducted using data from the 2008 to 2010 Korean National Health and
      Nutrition Examination Survey to evaluate the relationship between blood Hg and
      BMD and the prevalence of osteopenia or osteoporosis in 1,190 men over 50 years
      of age. BMD was measured by dual-energy X-ray absorptiometry. Osteopenia and
      osteoporosis were diagnosed for each body site according to World Health
      Organization T-score criteria. RESULTS: After adjusting for age, body mass index,
      caloric energy and calcium intake, vitamin D levels, fish consumption, alcohol
      consumption, smoking, and exercise, quartiles of blood Hg were positively
      associated with femur neck T-scores in multiple linear regression analysis
      (beta=0.06, P-value=0.03). Compared with the lowest blood Hg quartile, the odds
      ratios and 95% confidence intervals for diagnosis of osteopenia or osteoporosis
      in the second and fourth quartiles were 0.63 (0.41-0.99) and 0.57 (0.36-0.91),
      respectively, in the femur neck after adjusting for the same co-variables.
      CONCLUSION: High blood Hg levels were associated with reduced odds of decreased
      femur neck BMD in Korean men. However, subgroup analysis did not show a
      significant protective effect of blood Hg on osteoporotic fractures. Further
      research is necessary to clarify the association between blood Hg and BMD.

PMID- 27688861
TI  - Association between Physical Activity Levels and Physical Symptoms or Illness
      among University Students in Korea.
AB  - BACKGROUND: Low levels of physical activity can cause various physical symptoms
      or illness. However, few studies on this association have been conducted in young
      adults. The aim of this study was to investigate the association between physical
      activity levels and physical symptoms or illness in young adults. METHODS:
      Subjects were university students who participated in a web-based self
      administered questionnaire in a university in Seoul in 2013. We obtained
      information on physical activities and physical symptoms or illness in the past
      year. Independent variables were defined as symptoms or illness which were
      associated with decreased academic performance. Logistic regression was performed
      to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of each
      physical symptom or illness with adjustment for covariables. RESULTS: A total of
      2,201 participants were included in the study. The main physical symptoms or
      illness among participants were severe fatigue (64.2%), muscle or joint pain
      (46.3%), gastrointestinal problems (43.1%), headache or dizziness (38.6%),
      frequent colds (35.1%), and sleep problems (33.3%). Low physical activity levels
      were significantly associated with high ORs of physical symptoms or illness.
      Multivariable-adjusted ORs (95% CIs) in the lowest vs. highest tertile of
      physical activity were 1.45 (1.14-1.83) for severe fatigue, 1.35 (1.07-1.70) for
      frequent colds, and 1.29 (1.02-1.63) for headaches or dizziness. We also found
      that lower levels of physical activity were associated with more physical
      symptoms or bouts of illness. CONCLUSION: Low physical activity levels were
      significantly associated with various physical symptoms or illness among
      university students. Also, individuals in the lower levels of physical activity
      were more likely to experience more physical symptoms or bouts of illness than
      those in the highest tertile of physical activity.

PMID- 27688862
TI  - Association between Socioeconomic Status and Cancer Screening in Koreans over 40
      Years in Age Based on the 2010-2012 Korean National Health and Nutrition
      Examination Survey.
AB  - BACKGROUND: We investigated the association between socioeconomic status (SES)
      and cancer screening in a Korean population aged 40 years or older. METHODS: This
      cross-sectional study included 12,303 participants (5,284 men and 7,019 women)
      who participated in the 2010-2012 Korean National Health and Nutrition
      Examination Survey. Self-reported questionnaires were used to assess
      participant's SES (household income, occupational, and educational status) and
      cancer screening behavior. RESULTS: Compared to the lowest household income
      group, the odds ratios (ORs) (95% confidence intervals [CIs]) for overall cancer
      screening of the highest income group were 2.113 (1.606-2.781) in men and 1.476
      (1.157-1.883) in women; those for private cancer screening of the highest income
      group were 2.446 (1.800-3.324) in men and 2.630 (2.050-3.373) in women, while
      those for National Cancer Screening Programs (NCSP) in the highest income group
      were 1.076 (0.805-1.439) in men and 0.492 (0.388-0.623) in women. Compared to
      manual workers, ORs (95% CIs) for private cancer screening of office workers were
      1.300 (1.018-1.660) in men and 0.822 (0.616-1.098) in women. In comparison to the
      least educated men, OR (95% CI) for private cancer screening of the most educated
      men was statistically significant (1.530 [1.117-2.095]). CONCLUSION: Higher
      economic status was associated with higher rates of overall and private cancer
      screening in both sexes and a lower rate of NCSP in women. Male office workers
      and more educated individuals underwent private cancer screening at a higher rate
      than manual workers and less educated individuals, respectively.

PMID- 27688863
TI  - Prevalence and Predictive Factors of Sexual Dysfunction in Iranian Women:
      Univariate and Multivariate Logistic Regression Analyses.
AB  - BACKGROUND: Female sexual dysfunction, which can occur during any stage of a
      normal sexual activity, is a serious condition for individuals and couples. The
      present study aimed to determine the prevalence and predictive factors of female
      sexual dysfunction in women referred to health centers in Ilam, the Western Iran,
      in 2014. METHODS: In the present cross-sectional study, 444 women who attended
      health centers in Ilam were enrolled from May to September 2014. Participants
      were selected according to the simple random sampling method. Univariate and
      multivariate logistic regression analyses were used to predict the risk factors
      of female sexual dysfunction. Diffe rences with an alpha error of 0.05 were
      regarded as statistically significant. RESULTS: Overall, 75.9% of the study
      population exhibited sexual dysfunction. Univariate logistic regression analysis
      demonstrated that there was a significant association between female sexual
      dysfunction and age, menarche age, gravidity, parity, and education (P<0.05).
      Multivariate logistic regression analysis indicated that, menarche age (odds
      ratio, 1.26), education level (odds ratio, 1.71), and gravida (odds ratio, 1.59)
      were independent predictive variables for female sexual dysfunction. CONCLUSION:
      The majority of Iranian women suffer from sexual dysfunction. A lack of awareness
      of Iranian women's sexual pleasure and formal training on sexual function and its
      influencing factors, such as menarche age, gravida, and level of education, may
      lead to a high prevalence of female sexual dysfunction.

PMID- 27688864
TI  - Development of Epidural and Paraspinal Abscesses after Insufficient Evaluation
      and Treatment of Acute Pyelonephritis Caused by Staphylococcus aureus.
AB  - Diagnoses of pyelonephritis caused by Staphylococcus aureus should be accompanied
      by investigations of concomitant bladder obstruction and metastatic infections,
      especially to the spine or heart. Complicated pyelonephritis due to S. aureus
      requires more than 2 weeks of antibiotics, which is the typically recommended
      treatment duration for pyelonephritis. We describe a patient who was diagnosed
      with complicated epidural and paraspinal abscesses after insufficient evaluation
      and treatment of acute pyelonephritis due to S. aureus. A 62-year-old man with
      type 2 diabetes was admitted with fever, increased urinary frequency, and left
      flank pain. He was diagnosed with acute pyelonephritis caused by S. aureus. His
      fever and flank pain subsided after 3 days of intravenous antibiotics. Evaluation
      of bladder obstruction and metastatic infection were not performed, as he
      declined further evaluation. The patient was discharged with oral antibiotics and
      was requested to attend weekly appointments but was lost to follow-up. One month
      later, the patient presented at the outpatient clinic with similar symptoms.
      Computed tomography showed recurrent pyelonephritis and a distended bladder. His
      flank pain persisted despite administration of an opioid agent. Therefore,
      magnetic resonance imaging was performed, revealing epidural and paraspinal
      abscesses. Ultrasound-guided aspiration of the paraspinal muscle layer was
      performed, and blood and percutaneous aspirated fluid cultures revealed S. aureus
      growth. The pattern of antimicrobial sensitivity was identical to that at his
      first admission. Following more than 4 weeks of antibiotics, magnetic resonance
      imaging showed the abscesses had decreased in size. The patient was discharged
      without neurologic sequelae and was provided with oral antibiotics. 

PMID- 27688865
TI  - Patients' Perceived Quality of Family Physicians' Primary Care with or without
      'Family Medicine' in the Clinic Name.
AB  - BACKGROUND: Patients' perspectives of family medicine according to the
      physician's identity and role as a primary-care specialist need to be
      investigated. This study was conducted to investigate the perceived quality of
      the primary care of family medicine clinics as assessed by patients in a
      community setting. METHODS: Patients (or their guardians) visiting nine community
      family medicine clinics were surveyed using the Korean Primary Care Assessment
      Tool from April 2014 to June 2014. The scores of the Korean Primary Care
      Assessment Tool domains were compared according to the clinics' designation (or
      not) as 'family medicine' and the patients' recognition (or not) of the
      physicians as board-certified family medicine specialists. RESULTS: A total of
      196 subjects responded to the questionnaire. They assessed the community clinics'
      quality of primary care as moderate to high. Of the clinics, those that were not
      designated as family medicine scored higher than those that were designated as
      family medicine (P<0.05). The group of patients that recognized a clinic as that
      of a board-certified family medicine specialist awarded higher scores than the
      non-recognition group in the domains of coordination function and personalized
      care (P<0.05). CONCLUSION: The moderate to high scores for the community family
      medicine clinics' quality of primary care are encouraging. It seems that
      patients' recognition of the family physician's role and of the physician-patient
      relationship has a significant influence on their assessment of the quality of
      primary care.

PMID- 27688866
TI  - Comparison of Cancer Prevalence in Physicians with That of the General
      Population, and Important Considerations.

PMID- 27688867
TI  - An Analysis of Electronic Cigarette and Cigarette Advertising in US Women's
      Magazines.
AB  - BACKGROUND: Traditional cigarette advertising has existed in the US for over 200
      years. Studies suggest that advertising has an impact on the initiation and
      maintenance of smoking behaviors. In recent years, electronic cigarettes (e
      cigarettes) emerged on the market as an alternative to the traditional tobacco
      cigarette. The purpose of this study was to describe advertisements in popular US
      magazines marketed to women for cigarettes and e-cigarettes. METHODS: This study
      involved analyzing 99 issues of 14 popular US magazines marketed to women.
      RESULTS: Compared to advertisements for traditional cigarettes, advertisements
      for e-cigarettes were more often found in magazines geared toward the 31-40-year
      old audience (76.5% vs. 53.1%, P = 0.011) whereas traditional cigarette
      advertisements were nearly equally distributed among women 31-40 and >=40 years.
      More than three-quarters of the e-cigarette advertisements presented in magazines
      aimed at the higher median income households compared to a balanced distribution
      by income for traditional cigarettes (P = 0.033). CONCLUSIONS: Future studies
      should focus on specific marketing tactics used to promote e-cigarette use as
      this product increases in popularity, especially among young women smokers.

PMID- 27688868
TI  - Epidemiological Study of Animal Bites and Rabies in Lorestan Province in West of
      Iran During 2004-2014 for Preventive Purposes.
AB  - BACKGROUND: Despite the progress made, animal bites and rabies are one of the
      important health problems in the country. The purpose of this study was to
      investigate the epidemiology of animal bites and rabies during 2004-2014 in
      Lorestan Province to prevent them in population of the province for the future
      prospective aspects. MATERIALS AND METHODS: In a descriptive cross-sectional
      study, all those cases bitten in the province, during 2004 and 2014, were
      studied. The required information about the age, sex, the bitten organ, type of
      the invasive animal time, and location of the event were collected in
      questionnaires and then analyzed. RESULTS: The total number of cases of animal
      rabies during the period of study was 43,892, shown at the rate of 223.23 in
      100,000 people. Seventy-eight percent of animal bites in rural areas, 41.42% in
      the ages 10-29-year-old, 26.8% of cases were students, 56.77% leg bites, and
      82.5% of dog bites. Four cases of human rabies were observed during this period.
      CONCLUSIONS: Rate of animal bites and rabies is high in Lorestan Province.
      Controlling animals such as dogs and cats in the province through training people
      at risk, especially among the students, rural areas and inter-sectorial
      coordination to eliminate stray animals should be considered over and over.
      Preventive actions to avoid bites are a priority.

PMID- 27688869
TI  - Tobacco Use and Substance Abuse in Students of Karaj Universities.
AB  - BACKGROUND: It is clear that tobacco smoking and substance abuse have negative
      consequences on adolescent and youth's health. Tobacco smoking especially hookah
      smoking has increased worldwide especially among university students. This study
      aimed to determine the prevalence of risk-taking behaviors such as cigarette
      smoking, hookah smoking, alcohol use, and drug abuse and its predictors in
      students of Karaj universities. METHODS: This cross-sectional study took place in
      Karaj in January and February 2014. The randomly selected sample consisted of
      1959 college students. A self-administered questionnaire was used to measure risk
      taking behaviors as well as demographic and related risk factors. Logistic
      regression model was performed in data analysis. RESULTS: The prevalence of
      cigarette smoking was 9.3%. The prevalence of hookah smoking was 9.3%. 7% of
      students used illegal drugs and 9.5% of students used alcohol at least once in
      last 30 days. After adjustment for other factors, being male, living without
      parents, having smoker friends, and presence any smoker in the family were
      factors associated with students' risk-taking behaviors. The results showed the
      co-occurrence of risk-taking behaviors. CONCLUSIONS: The prevalence of tobacco
      smoking and substance abuse, particular in males, are high. It seems that
      planning preventive interventions for this part of the population are necessary.
      This study emphasized the co-occurrence of risky behaviors, so, it is better high
      risk behaviors simultaneously targeted at reducing or preventing interventions.

PMID- 27688870
TI  - Sex-specific effects of dietary fatty acids on saliva cortisol and social
      behavior in guinea pigs under different social environmental conditions.
AB  - BACKGROUND: Unbalanced dietary intakes of saturated (SFAs) and polyunsaturated
      (PUFAs) fatty acids can profoundly influence the hypothalamic-pituitary-adrenal
      (HPA)-axis and glucocorticoid secretions in relation to behavioral performances.
      The beneficial effects of higher dietary PUFA intakes and PUFA:SFA ratios may
      also affect social interactions and social-living per se, where adequate
      physiological and behavioral responses are essential to cope with unstable social
      environmental conditions. METHODS: Effects of diets high in PUFAs or SFAs and a
      control diet were investigated in male and female guinea pigs after 60 days of
      supplementation. Plasma fatty acid patterns served as an indicator of the general
      fatty acid status. HPA-axis activities, determined by measuring saliva cortisol
      concentrations, social behaviors, and hierarchy ranks were analyzed during group
      housing of established single-sexed groups and during challenging social
      confrontations with unfamiliar individuals of the other groups. RESULTS: The
      plasma PUFA:SFA ratio was highest in PUFA supplemented animals, with female
      levels significantly exceeding males, and lowest in SFA animals. SFA males and
      females showed increased saliva cortisol levels and decreased aggressiveness
      during group housing, while sociopositive behaviors were lowest in PUFA males.
      Males generally showed higher cortisol increases in response to the challenging
      social confrontations with unfamiliar individuals than females. While increasing
      cortisol concentrations were detected in control and PUFA animals, no such effect
      was found in SFA animals. During social confrontations, PUFA males showed higher
      levels of agonistic and sociopositive behaviors and also gained higher dominance
      ranks among males, which was not detected for females. CONCLUSIONS: While SFAs
      seemingly impaired cortisol responses and social behaviors, PUFAs enabled
      adequate behavioral responses in male individuals under stressful new social
      environmental conditions. This sex-specific effect was possibly related to a
      general sex difference in the n-3 PUFA bioavailability and cortisol responses,
      which may indicate that males are more susceptible to changing environmental
      conditions, and shows how dietary fatty acids can shape social systems.

PMID- 27688871
TI  - Reduction of apoptosis and preservation of mitochondrial integrity under
      ischemia/reperfusion injury is mediated by estrogen receptor beta.
AB  - BACKGROUND: Estrogen improves cardiac recovery after ischemia/reperfusion (I/R)
      by yet incompletely understood mechanisms. Mitochondria play a crucial role in
      I/R injury through cytochrome c-dependent apoptosis activation. We tested the
      hypothesis that 17beta-estradiol (E2) as well as a specific ERbeta agonist
      improve cardiac recovery through estrogen receptor (ER)beta-mediated mechanisms
      by reducing mitochondria-induced apoptosis and preserving mitochondrial
      integrity. METHODS: We randomized ovariectomized C57BL/6N mice 24h before I/R to
      pre-treatment with E2 or a specific ERbeta agonist (ERbetaA). Isolated hearts
      were perfused for 20min prior to 30min global ischemia followed by 40min
      reperfusion. RESULTS: Compared with controls, ERbetaA and E2 treated groups
      showed a significant improvement in cardiac recovery, i.e. an increase in left
      ventricular developed pressure, dP/dtmax and dP/dtmin. ERbetaA and E2 pre
      treatment led to a significant reduction in apoptosis with decreased cytochrome c
      release from the mitochondria and increased mitochondrial levels of anti
      apoptotic Bcl2 and ACAA2. Protein levels of mitochondrial translocase inner
      membrane (TIM23) and mitochondrial complex I of respiratory chain were increased
      by ERbetaA and E2 pre-treatment. Furthermore, we found a significant increase of
      myosin light chain 2 (MLC2) phosphorylation together with ERK1/2 activation in
      E2, but not in ERbetaA treated groups. CONCLUSIONS: Activation of ERbeta is
      essential for the improvement of cardiac recovery after I/R through the
      inhibition of apoptosis and preservation of mitochondrial integrity and can be a
      achieved by a specific ERbeta agonist. Furthermore, E2 modulates MLC2 activation
      after I/R independent of ERbeta.

PMID- 27688872
TI  - Anticancer bioactive peptide-3 inhibits human gastric cancer growth by targeting
      miR-338-5p.
AB  - BACKGROUND: Cancer incidence and mortality have been increasing in China, making
      cancer the leading cause of death since 2010 and a major public health concern in
      the country. Cancer stem cells have been studied in relation to the treatment of
      different malignancies, including gastric cancer. Anticancer bioactive peptide-3
      (ACBP-3) can induce the apoptosis of gastric cancer stem cells (GCSCs) and reduce
      their tumorigenicity. In the present study, for the first time, we used a miRNA
      microarray and bioinformatics analysis to identify differentially expressed
      miRNAs in ACBP-3-treated GCSCs and GCSC-derived tumors in a xenograft model and
      functionally verified the identified miRNAs. miR-338-5p was selected based on its
      significant upregulation by ACBP-3 both in cultured GCSCs and in tumor tissues.
      RESULTS: miR-338-5p was downregulated in GCSCs compared with normal gastric
      epithelial cells, and the ectopic restoration of miR-338-5p expression in GCSCs
      inhibited cell proliferation and induced apoptosis, which correlated with the
      upregulation of the pro-apoptotic Bcl-2 proteins BAK and BIM. We also found that
      ACBP-3-treated GCSCs could respond to lower effective doses of cisplatin (DDP) or
      5-fluorouracil (5-FU), possibly because ACBP-3 induced the expression of miR-338
      5p and the BAK and BIM proteins and promoted GCSC apoptosis. CONCLUSIONS: Our
      data indicate that miR-338-5p is part of an important pathway for the inhibition
      of human gastric cancer stem cell proliferation by ACBP-3 combined with
      chemotherapeutics. ACBP-3 could suppress GCSC proliferation and lower the
      required effective dose of cisplatin or 5-fluorouracil. Therefore, this study
      provides not only further evidence for the remarkable anti-tumor effect of ACBP-3
      but also a possible new approach for the development of GCSC-targeting therapies.

PMID- 27688873
TI  - The cost and value of cancer drugs - are new innovations outpacing our ability to
      pay?
AB  - Cancer drug expenditures have been increasing significantly in countries around
      the world. A recent paper in the IJHPR provides new knowledge and insights into
      this global phenomenon by analyzing how it is playing out in an Israeli health
      plan with over two million members, whose state-of-the-art information systems
      provide an opportunity to explore these changes in a comprehensive, detailed and
      reliable manner. There is a wide variation in both the cost-effectiveness and the
      budget impact of individual drugs. These issues also vary when analyzing drugs in
      other countries due to differential pricing mechanisms. In addition to drug
      expenditure, the overall cost of cancer care is increasing, partly due to
      expenditures on non-pharmacologic treatments and diagnostic testing. With the
      arrival of new therapies, the future of cancer care is exciting. However, there
      will be many challenges ahead with regard to the ability to pay for such
      innovations. In this commentary we discuss the current problems and anticipate
      the future challenges. 

PMID- 27688874
TI  - Medical education in Israel 2016: five medical schools in a period of transition.
AB  - ABSTRACT: We reviewed the existing programs for basic medical education (BME) in
      Israel as well as their output, since they are in a phase of reassessment and
      transition. The transition has been informed, in part, by evaluation in 2014 by
      an International Review Committee (IRC). The review is followed by an analysis of
      its implications as well as the emergent roadmap for the future. The review
      documents a trend of modernizing, humanizing, and professionalizing Israeli
      medical education in general, and BME in particular, independently in each of the
      medical schools. Suggested improvements include an increased emphasis on
      interactive learner-centered rather than frontal teaching formats, clinical
      simulation, interprofessional training, and establishment of a national medical
      training forum for faculty development. In addition, collaboration should be
      enhanced between medical educators and health care providers, and among the
      medical schools themselves. The five schools admitted about 730 Israeli students
      in 2015, doubling admissions from 2000. In 2014, the number of new licenses,
      including those awarded to Israeli international medical graduates (IMGs),
      surpassed for the first time in more than a decade the estimated need for 1100
      new physicians annually. About 60 % of the licenses awarded in 2015 were to IMGs.
      CONCLUSIONS: Israeli BME is undergoing continuous positive changes, was supplied
      with a roadmap for even further improvement by the IRC, and has doubled its
      output of graduates. The numbers of both Israeli graduates and IMGs are higher
      than estimated previously and may address the historically projected physician
      shortage. However, it is not clear whether the majority of newly licensed
      physicians, who were trained abroad, have benefited from similar recent
      improvements in medical education similar to those benefiting graduates of the
      Israeli medical schools, nor is it certain that they will benefit from the
      further improvements that have recently been recommended for the Israeli medical
      schools. Inspired by the IRC report, this overview of programs and the updated
      physician manpower data, we hope the synergy between all stakeholders is enhanced
      to address the combined medical education quality enhancement and output
      challenge.

PMID- 27688875
TI  - Proficiency testing of skin prick testers as part of a quality assurance system.
AB  - BACKGROUND: Skin prick test is an important diagnostic procedure in clinical
      allergy but documentation of the quality is often missing. METHODS: We describe a
      proficiency system to evaluate staff members in relation to the international
      recommended reproducibility in terms of coefficient of variation (CV < 40 %) and
      the linearity (coefficient of regression >0.85) based on blinded octuplicate
      histamine testing using histamine 3, 10, 30 and 100 mg/ml. RESULTS: Fourteen
      trained allergy nurses participated in the proficiency testing. More than 95 % of
      the nurses, generated coefficient of variation less than 40 %, and for around 35
      % of testers the CV were below 20 % based on wheal area. Regarding the linearity
      (coefficient of regression), only two nurses produced tests with a value below
      0.85. On the contrary, 79 % of testers demonstrated a coefficient of regression
      >0.95. Depending on the gentleness of the prick procedure, the inter-nurse
      variability in wheal area varied more than twofold corresponding to a 10-doubling
      of histamine concentration. This would never have been detected without using a
      proficiency testing system. CONCLUSION: The described histamine testing provides
      an objective system for the evaluation of basic skin test quality assessment
      standards especially for documentation in scientific studies.

PMID- 27688876
TI  - Emergence of linezolid- and vancomycin-resistant Enterococcus faecium in a
      department for hematologic stem cell transplantation.
AB  - BACKGROUND: Prevalence of vancomycin-resistant enterococci has increased in
      Germany. Here, we report the cluster of linezolid- and vancomycin-resistant
      Enterococcus faecium (LVRE) in a German department for hematologic stem cell
      transplantation (HSCT). METHODS: In this retrospective analysis we included all
      patients with LVRE in a university-based department for HSCT in 2014 and 2015.
      Patients chart reviews were used to investigate the epidemiology and clinical
      outcome. Available LVRE isolates underwent detailed microbiological
      characterization and genotyping by pulsed-field gel electrophoresis (PFGE).
      RESULTS: In total, 20 patients with LVRE were identified within the observed time
      period. All except two patients underwent allogeneic HSCT. Surveillance culture
      results from incoming patients and chart review revealed that 10 of 20 patients
      were colonized at hospital admission. Eight of 10 patients with in-hospital
      acquired LVRE had previous linezolid treatment. Analysis of spatio-temporal
      patterns showed no evidence for LVRE patient-to-patient or environment-to-patient
      transmission within the HSCT department. In five cases (25 %) LVRE bloodstream
      infection occurred. Nine LVRE isolates could be saved for characterization. Eight
      isolates carried vanA, one isolate vanB. PFGE analysis showed that four different
      LVRE clones were responsible for the cluster. One single genotype was present in
      six LVRE isolates whereupon the corresponding patients were all referred from the
      same hospital to the HSCT department. CONCLUSIONS: This is the first report
      demonstrating the emergence of LVRE in a German HSCT department. (L)VRE screening
      at patients' admission and appropriate infection control strategies were
      sufficient to prevent any transmission. Further studies in this predisposed
      patient collective are warranted.

PMID- 27688877
TI  - Identifying conditions for elimination and epidemic potential of methicillin
      resistant Staphylococcus aureus in nursing homes.
AB  - BACKGROUND: Residents of nursing homes are commonly colonized with methicillin
      resistant Staphylococcus aureus (MRSA) but there is a limited understanding of
      the dynamics and determinants of spread in this setting. To address this gap, we
      sought to use mathematical modeling to assess the epidemic potential of MRSA in
      nursing homes and to determine conditions under which non-USA300 and USA300 MRSA
      could be eliminated or reduced in the facilities. METHODS: Model parameters were
      estimated from data generated during a longitudinal study of MRSA in 6 Wisconsin
      nursing homes. The data included subject colonization status with strain-specific
      MRSA collected every 3 months for up to 1 year. Deterministic and stochastic co
      colonization and single-strain models were developed to describe strain-specific
      dynamics of MRSA in these facilities. Basic reproduction numbers of strain
      independent MRSA, non-USA300 and USA300 MRSA were estimated numerically. The
      impact of antibiotic use in the past 3 months on the prevalence of strain
      specific MRSA and associated basic reproduction numbers were evaluated. RESULTS:
      Our models predicted that MRSA would persist in Wisconsin nursing homes, and non
      USA300 would remain the dominant circulating strain. MRSA eradication was
      theoretically achievable by elimination of MRSA-positive admissions over the
      course of years. Substantial reductions in MRSA prevalence could be attained
      through marked increase in clearance rates or reduction in MRSA-positive
      admissions sustained over years. The basic reproduction number of strain
      independent MRSA was 0.18 (95 % CI = 0.13-0.23). Recent antibiotic use increased
      the prevalence of strain-specific MRSA and associated basic reproduction numbers,
      but was unlikely to lead to an outbreak. CONCLUSIONS: Based on our model, MRSA
      elimination from nursing homes, while theoretically possible, was unlikely to be
      achieved in practice. Decolonization therapy that can sustain higher clearance
      rates or lower MRSA-positive introductions over years may reduce strain-specific
      prevalence of MRSA in the facilities, and antibiotic stewardship may contribute
      to this effort. Large-scale MRSA outbreaks were unlikely in this setting.

PMID- 27688878
TI  - How rare bone diseases have informed our knowledge of complex diseases.
AB  - Rare bone diseases, generally defined as monogenic traits with either autosomal
      recessive or dominant patterns of inheritance, have provided a rich database of
      genes and associated pathways over the past 2-3 decades. The molecular genetic
      dissection of these bone diseases has yielded some major surprises in terms of
      the causal genes and/or involved pathways. The discovery of genes/pathways
      involved in diseases such as osteopetrosis, osteosclerosis, osteogenesis
      imperfecta and many other rare bone diseases have all accelerated our
      understanding of complex traits. Importantly these discoveries have provided
      either direct validation for a specific gene embedded in a group of genes within
      an interval identified through a complex trait genome-wide association study
      (GWAS) or based upon the pathway associated with a monogenic trait gene, provided
      a means to prioritize a large number of genes for functional validation studies.
      In some instances GWAS studies have yielded candidate genes that fall within
      linkage intervals associated with monogenic traits and resulted in the
      identification of causal mutations in those rare diseases. Driving all of this
      discovery is a complement of technologies such as genome sequencing,
      bioinformatics and advanced statistical analysis methods that have accelerated
      genetic dissection and greatly reduced the cost. Thus, rare bone disorders in
      partnership with GWAS have brought us to the brink of a new era of personalized
      genomic medicine in which the prevention and management of complex diseases will
      be driven by the molecular understanding of each individuals contributing genetic
      risks for disease. 

PMID- 27688879
TI  - Selective ligninolysis of wheat straw and wood chips by the white-rot fungus
      Lentinula edodes and its influence on in vitro rumen degradability.
AB  - BACKGROUND: The present work investigated the influence of lignin content and
      composition in the fungal treatment of lignocellulosic biomass in order to
      improve rumen degradability. Wheat straw and wood chips, differing in lignin
      composition, were treated with Lentinula edodes for 0, 2, 4, 8 and 12 wk and the
      changes occurring during fungal degradation were analyzed using pyrolysis-gas
      chromatography-mass spectrometry and detergent fiber analysis. RESULTS: L. edodes
      preferentially degraded lignin, with only limited cellulose degradation, in wheat
      straw and wood chips, leaving a substrate enriched in cellulose. Syringyl (S)
      lignin units were preferentially degraded than guaiacyl (G)-lignin units,
      resulting in a decreased S/G ratio. A decreasing S/G ratio (wheat straw: r = 
      0.72, wood chips: r = -0.75) and selective lignin degradation (wheat straw: r = 
      0.69, wood chips: r = -0.88) were correlated with in vitro gas production (IVGP),
      a good indicator for rumen degradability. CONCLUSIONS: L. edodes treatment
      increased the IVGP of wheat straw and wood chips. Effects on IVGP were similar
      for wheat straw and wood chips indicating that lignin content and 3D-structure of
      cell walls influence in vitro rumen degradability more than lignin composition.

PMID- 27688880
TI  - Associations between psychological factors and the effect of home-based physical
      exercise in women with chronic neck and shoulder pain.
AB  - BACKGROUND: Exercise is often used in the treatment of chronic neck and shoulder
      muscle pain. It is likely that psychological aspects have an impact on the
      results of exercise-based treatments. OBJECTIVES: (1) To examine the associations
      between psychological factors and the effect of a home-based physical exercise
      intervention. (2) To examine differences in psychological factors at baseline
      between (a) subjects who continued in the trial and those who did not and (b)
      subjects who completed the intervention and those who did not. METHOD: A total of
      57 women with chronic neck and shoulder pain were included in a home-based
      exercise intervention trial. Pain intensity, disability, and psychological
      factors (anxiety and depression symptoms, catastrophizing, fear-avoidance
      beliefs, self-efficacy, and pain acceptance) were measured at baseline, after 4-6
      months, and after 1 year of exercise. Associations between the psychological
      factors and changes in pain intensity and disability were analysed, as well as
      differences in psychological factors at baseline between subjects who continued
      in and completed the intervention, and those who did not. RESULTS: Associations
      between positive changes in pain intensity and disability were found for low fear
      avoidance beliefs and low-pain self-efficacy at baseline. In addition, fear
      avoidance beliefs at baseline were higher in the subjects who dropped out of the
      intervention than in those who continued. Pain acceptance at baseline was higher
      in the subjects who completed the intervention at the end of the trial.
      CONCLUSION: Particularly, fear-avoidance beliefs and pain self-efficacy should be
      taken into consideration when implementing home-based physical exercise as
      treatment for chronic neck pain. In addition, high pain acceptance might improve
      the adherence to prescribed exercise.

PMID- 27688883
TI  - First case of a dog bite wound infection caused by Streptococcus minor in human.
AB  - We report the first case of human infection caused by Streptococcus minor in a 51
      year-old immunocompetent woman admitted for dog bite injuries. At present, the
      role of Streptococcus minor in bite wound infections is unknown. Further studies
      on virulence factors are needed to elucidate its pathogenicity mechanisms. 

PMID- 27688881
TI  - MR thermometry for focused ultrasound monitoring utilizing model predictive
      filtering and ultrasound beam modeling.
AB  - BACKGROUND: A major challenge in using magnetic resonance temperature imaging
      (MRTI) to monitor focused ultrasound (FUS) applications is achieving high spatio
      temporal resolution over a large field of view (FOV). This is important to
      accurately monitor all ultrasound (US) power depositions. Magnetic resonance (MR)
      subsampling in conjunction with thermal model-based reconstruction of the MRTI
      utilizing Pennes bioheat transfer equation (PBTE) is one promising approach. The
      thermal properties used in the thermal model are often estimated from a pre
      treatment, low-power sonication. METHODS: In this proof-of-concept study we
      investigate the use of US simulations computed using the hybrid angular spectrum
      (HAS) method to estimate the US power deposition density Q, thereby avoiding the
      pre-treatment sonication and any potential tissue damage. MRTI reconstructions
      are performed using a thermal model-based reconstruction method called model
      predictive filtering (MPF). Experiments are performed in a homogeneous gelatin
      phantom and in a gelatin phantom with embedded plastic skull. MPF reconstructions
      are compared to separate sonications imaged with fully sampled data over a
      smaller FOV. Temperature root-mean-square errors (RMSE) and focal spot positions
      and shapes are evaluated. RESULTS: HAS simulations accurately predict the
      location of the focal spot (to within 1 mm) in both phantoms. Accurate
      temperature maps (RMSE below 1  degrees C), where the location of the focal spot
      agrees well with fully sampled "truth" (to within 1 mm), are also achieved in
      both phantoms. CONCLUSIONS: HAS simulations can be used to accurately predict the
      focal spot location in homogeneous media and when focusing through an aberrating
      plastic skull. The HAS simulated power deposition (Q) patterns can be used in the
      MPF thermal model-based reconstruction to obtain accurate temperature maps with
      high spatio-temporal resolution over large FOVs.

PMID- 27688882
TI  - A spherical-plot solution to linking acceleration metrics with animal
      performance, state, behaviour and lifestyle.
AB  - BACKGROUND: We are increasingly using recording devices with multiple sensors
      operating at high frequencies to produce large volumes of data which are
      problematic to interpret. A particularly challenging example comes from studies
      on animals and humans where researchers use animal-attached accelerometers on
      moving subjects to attempt to quantify behaviour, energy expenditure and
      condition. RESULTS: The approach taken effectively concatinated three complex
      lines of acceleration into one visualization that highlighted patterns that were
      otherwise not obvious. The summation of data points within sphere facets and
      presentation into histograms on the sphere surface effectively dealt with data
      occlusion. Further frequency binning of data within facets and representation of
      these bins as discs on spines radiating from the sphere allowed patterns in
      dynamic body accelerations (DBA) associated with different postures to become
      obvious. METHOD: We examine the extent to which novel, gravity-based spherical
      plots can produce revealing visualizations to incorporate the complexity of such
      multidimensional acceleration data using a suite of different acceleration
      derived metrics with a view to highlighting patterns that are not obvious using
      current approaches. The basis for the visualisation involved three-dimensional
      plots of the smoothed acceleration values, which then occupied points on the
      surface of a sphere. This sphere was divided into facets and point density within
      each facet expressed as a histogram. Within each facet-dependent histogram, data
      were also grouped into frequency bins of any desirable parameters, most
      particularly dynamic body acceleration (DBA), which were then presented as discs
      on a central spine radiating from the facet. Greater radial distances from the
      sphere surface indicated greater DBA values while greater disc diameter indicated
      larger numbers of data points with that particular value. CONCLUSIONS: We
      indicate how this approach links behaviour and proxies for energetics and can
      inform our identification and understanding of movement-related processes,
      highlighting subtle differences in movement and its associated energetics. This
      approach has ramifications that should expand to areas as disparate as disease
      identification, lifestyle, sports practice and wild animal ecology. UCT Science
      Faculty Animal Ethics 2014/V10/PR (valid until 2017).

PMID- 27688884
TI  - Use of a fictitious community-based virtual teaching platform to aid in the
      teaching of pharmacy practice skills: Student perspectives after initial
      implementation.
AB  - BACKGROUND: Providing patient-centred care requires pharmacy students to learn
      how to interact effectively and understand individual differences that can
      influence patients' health. The School of Pharmacy at The University of Auckland,
      New Zealand (NZ), developed a virtual teaching platform, called NZ Pharmville,
      which consisted of twenty-one community-based patients who are members of six
      families; each family had a video vignette associated with it. Bachelor of
      Pharmacy (BPharm) students, enrolled in the third year pharmacy practice course,
      were able to view these recorded vignettes as part of their weekly pre-laboratory
      work for the course. All the clinical cases within the course were based on this
      community, with the aim of increasing the realism in the practical sessions and
      increasing patient-centred learning. This study aimed to explore the perspectives
      of pharmacy students regarding the integration of this virtual community into a
      third year undergraduate pharmacy practice course. METHODS: An anonymous,
      voluntary survey which consisted of twenty-one items, 13 requiring a Likert scale
      response and 8 requiring free text responses, was distributed to all students who
      had completed the third year pharmacy practice course. The responses to the
      questions were collated and analysed. Responses to questions one to thirteen were
      recorded in Excel, and results were presented as the combination of strongly
      agree and agree, strongly disagree and disagree and neutral. Responses to free
      text questions were read multiple times before being coded by two members of the
      research team into broad themes aligned to the overall aims of the evaluation.
      RESULTS: Eighty-six (80.4 %) of the eligible students completed the survey and
      the majority of responses were positive towards the benefits of using the virtual
      community in the course. Responses indicated that many of the students found the
      integration of the virtual community to be useful preparation for their practical
      sessions and the majority of students felt that the vignettes made it easier to
      develop empathy for the patients rather than reading about them. CONCLUSION: The
      use of virtual communities, for example, NZ Pharmville, show promise as a
      platform to aid in teaching and learning. The resources in NZ Pharmville allow
      students ongoing access to patient video clips that attempt to depict a real life
      situation, and enable students to engage with the fictional characters. The
      virtual community provided an educational experience which was well received by
      students. This teaching method appeared to promote active patient-centered
      learning and allowed students to reflect on and revisit these skills on a weekly
      basis.

PMID- 27688885
TI  - The fate of the new pharmacy bill: going backwards or forwards?
AB  - BACKGROUND: The proposed Pharmacy Bill of Malaysia which served to consolidate
      and harmonise the existing pharmacy legislation which has been used for more than
      60 years. This new Pharmacy Bill contains 17 parts and a total of 170 legislative
      sections covering laws governing pharmacy practice, medicinal products
      classification, registration, sale, supply, licensing etc. Our article could
      serve as a case study on pharmacy jurisprudence and drug regulation as well as
      the governance for medicines. DISCUSSION: Changes to the colonial era legislation
      are long overdue as the present pharmaceutical and medical controls are not
      integrated and various overlaps exist in terms of roles of control. However,
      various organisations of private general practitioners strongly opposed this
      Pharmacy Bill and lobbied for a revised version that greatly favours themselves.
      Thus, the latest revision of this Pharmacy Bill renders the power to medical
      doctors to not only continue selling and supplying medications but also compound
      medication. SUMMARY: A complete overhaul of pharmacy legislation in view of the
      current challenges faced in providing efficient and comprehensive health services
      in Malaysia is necessary. For the sake of patients' safety and good governance
      for medicines, the private general practitioners should empower the patients with
      their needs for prescription and itemised billing. The proposed Pharmacy Bill
      could make the whole mechanism of managing and controlling the use of medicines
      more transparent and synchronised.

PMID- 27688886
TI  - Forces influencing generic drug development in the United States: a narrative
      review.
AB  - BACKGROUND: The United States (U.S.) Food and Drug Administration, as protectors
      of public health, encourages generic drug development and use so that patients
      can access affordable medications. The FDA, however, has limited mechanisms to
      encourage generic drug manufacturing. MAIN RESULTS: Generic drug manufacturers
      make decisions regarding development of products based on expected profitability,
      influenced by market forces, features of the reference listed drug, and
      manufacturing capabilities, as well as regulatory restrictions. Barriers to the
      development of generic drugs include the challenge of demonstrating
      bioequivalence of some products, particularly those that are considered to be
      complex generics. CONCLUSIONS: We present here a focused review describing the
      influences on generic manufacturers who are prioritizing drugs for generic
      development. We also review proposed strategies that regulators may use to
      incentivize generic drug development.

PMID- 27688887
TI  - Assessment of WHO/INRUD core drug use indicators in two tertiary care hospitals
      of Bahawalpur, Punjab, Pakistan.
AB  - BACKGROUND: Medicines are a main therapeutic intervention provided within
      hospitals and their proper use in the outpatient setting is important for
      patients and the community. The objective of this study was to evaluate drug use
      patterns in the outpatient departments (OPDs) of two tertiary care hospitals
      (Bahawal Victoria Hospital and Civil Hospital) in the Bahawalpur district of the
      Punjab province of Pakistan by employing the standard World Health
      Organization/International Network of Rational Use of Drugs (WHO/INRUD) drug use
      indicators. METHODS: A descriptive, cross-sectional study design was employed.
      For assessing the prescribing indicators a sample of 2400 prescriptions were
      systematically reviewed out of a total of 1,560,000 prescriptions written from
      1st April 2014 to 31st March 2015. A total of 600 randomly selected patients and
      all pharmacy personnel were observed and interviewed to investigate the patient
      care and facility-specific indicators. We used the published ideal standards for
      each of the WHO/INRUD indicators for comparison purposes. RESULTS: Among the
      prescribing indicators, the average number of drugs per prescription was 2.8 (SD
      = 1.3), the drugs prescribed by generic name were 56.6 %, the encounters with an
      antibiotic prescribed were 51.5 %, no injections were prescribed and 98.8 % of
      the drugs prescribed were from the Essential Drugs List (EDL). Among the patient
      care indicators, the average consultation time was 1.2 min (SD = 0.8), the
      average dispensing time was 8.7 s (SD = 4.9), the percentage of drugs actually
      dispensed was 97.3 %, the percentage of drugs adequately labeled was 100 % and
      the patients' knowledge of correct dosage schedule was 61.6 %. Among the facility
      specific indicators, all OPDs had a copy of the EDL and 72.4 % of the key drugs
      were available in stock. CONCLUSION: Irrational use of drugs was observed in both
      OPDs. Polypharmacy, brand prescribing, over-prescribing of antibiotics, short
      consultation and dispensing times, lack of patients' knowledge about prescribed
      medicines and unavailability of all key drugs in stock were the major issues that
      need attention of the healthcare authorities. This study necessitates the
      requirement to implement the relevant WHO recommended core interventions to
      promote rational use of medicines in these hospital-based OPDs.

PMID- 27688888
TI  - Comparisons of hearing threshold changes in male workers with unilateral
      conductive hearing loss exposed to workplace noise: a retrospective cohort study
      for 8 years.
AB  - BACKGROUND: The purpose of this study was to investigate hearing threshold
      changes of workers with unilateral conductive hearing loss who were exposed to
      workplace noise for 8-years. METHODS: Among 1819 workers at a shipyard in Ulsan,
      78 subjects with an air-bone gap >=10 dBHL in unilateral ears were selected.
      Factors that could affect hearing were acquired from questionnaires, physical
      examinations, and biochemistry examinations. Paired t-test was conducted to
      compare the hearing threshold changes over time between conductive hearing loss
      (CHL) ear and sensorineural hearing loss (SNHL) ear. RESULTS: The study included
      male subjects aged 48.7 +/- 2.9, having worked for 29.8 +/- 2.7 years. Hearing
      thresholds increased significantly in CHL ears and SNHL ears at all frequencies
      (0.5-6 kHz) during follow-up period (p < 0.05). The threshold change at 4 kHz was
      3.2 dBHL higher in SNHL ears which was statistically significant (p < 0.05). When
      workers were exposed to noise levels of 85 dBA and above, threshold change at 4
      kHz was 5.6 dBHL higher in SNHL ears which was statistically significant (p <
      0.05). Among workers aged below 50, the threshold change values were lower in low
      frequency (0.5-2 kHz) in SNHL ears, with a small range of changes, whereas in
      high-frequency (3-6 kHz), the range of changes was greater SNHL ears (p < 0.05).
      Among workers aged 50 and above, SNHL ears showed a wider range of changes in
      both high- and low-frequency areas (p < 0.05). CONCLUSIONS: At high-frequencies,
      particularly at 4 kHz, the range of hearing threshold changes was lower in ears
      with conductive hearing loss than in contralateral ears. This is suggested as a
      protective effect against noise exposure.

PMID- 27688889
TI  - Comparative analysis of Cucurbita pepo metabolism throughout fruit development in
      acorn squash and oilseed pumpkin.
AB  - Both the fruit mesocarp and the seeds of winter squash can be used for
      consumption, although the focus of breeding efforts varies by cultivar. Cultivars
      bred for fruit consumption are selected for fruit mesocarp quality traits such as
      carotenoid content, percent dry matter, and percent soluble solids, while these
      traits are essentially ignored in oilseed pumpkins. To compare fruit development
      in these two types of squash, we sequenced the fruit transcriptome of two
      cultivars bred for different purposes: an acorn squash, 'Sweet REBA', and an
      oilseed pumpkin, 'Lady Godiva'. Putative metabolic pathways were developed for
      carotenoid, starch, and sucrose synthesis in winter squash fruit and squash
      homologs were identified for each of the structural genes in the pathways. Gene
      expression, especially of known rate-limiting and branch point genes,
      corresponded with metabolite accumulation both across development and between the
      two cultivars. Thus, developmental regulation of metabolite genes is an important
      factor in winter squash fruit quality. 

PMID- 27688891
TI  - Longitudinal changes in desired body weight compared to changes in body weight:
      evidence of adaptation to weight gain?
AB  - BACKGROUND: Overweight individuals desire a lower weight than they actually have.
      Little is known on the extent to which this discrepancy is reduced over time due
      to adaptation or resignation. The aim of this study is to describe cross
      sectional relationships and longitudinal changes in desired body weight and
      differences between actual and desired body weight according to gender, age and
      category of body mass index in a large, adult cohort in Tromso, Norway. METHODS:
      Cross-sectional analyses of 8960 men and 9992 women aged 25-69 participating in
      Tromso 4 (during 1994-1995), and longitudinal analyses of 3210 men and 3689 women
      participating in both Tromso 4 (during 1994-1995) and Tromso 6 (during 2007
      2008). Simple descriptive statistics and linear regression was used to describe
      actual and desired weight, the difference between them, and how gender and age
      are related to the changes in actual and desired weight over this 13-year period.
      RESULTS: The difference between actual and desired body weight was largest for
      the obese and higher among the overweight than the normal weight for both
      genders. While normal weight men were quite satisfied with their body weight,
      normal weight women were not. Actual weight increased more than desired weight
      for all age groups and both genders except the oldest women. The difference
      between change in actual body weight and change in desired body weight during the
      13-year follow-up was significantly larger among men (2.0 kg) than women (1.5 kg)
      (p < 0.001), and larger among young than older adults (p < 0.001). Adjusting for
      level of education had no impact on this relationship. Furthermore, the
      association between age and the difference between change in actual body weight
      during the 13 years and change in desired body weight in the same period did not
      differ between men and women and, in gender specific analyses, between subjects
      with normal weight and those who were overweight or obese at start of follow-up.
      CONCLUSION: Older people adapt more to weight gain than younger age groups, with
      clear gender differences. Further studies of longitudinal changes in desired
      weight are warranted.

PMID- 27688892
TI  - Changes in waist circumference and the prevalence of abdominal obesity during
      1994-2008 - cross-sectional and longitudinal results from two surveys: the Tromso
      Study.
AB  - BACKGROUND: Abdominal obesity increases all-cause mortality and is a risk factor
      for a number of diseases. There are few population-based studies of the
      longitudinal changes of abdominal obesity. METHODS: Based on data from the Tromso
      Study, we studied gender- and age-specific mean waist circumference and
      prevalence of abdominal overweight and abdominal obesity in two surveys in 1994
      1995 (Tromso 4, 6812 men and women aged 25 to 84) and 2007-2008 (Tromso 6, 12,493
      men and women aged 30 to 87). Furthermore, we describe the longitudinal changes
      of waist circumference and abdominal obesity during 13 years in 3144 subjects
      (aged 25-69 in 1994) who attended both surveys. RESULTS: Cross-sectional analyses
      found a higher mean waist circumference in men than women and a direct
      relationship with age in both men and women in both Tromso 4 and in Tromso 6. As
      the WHO cut-off points for abdominal obesity are gender-specific, however, the
      prevalence of abdominal obesity was lower in men than in women. In 2007-2008,
      approximately 37 and 55 % of men and women, respectively, were classified as
      abdominally obese. Thirteen years before, in 1994-1995, the corresponding figures
      were 20 and 35 %. Longitudinal analyses of changes during the 13-year period
      clearly demonstrated that mean waist circumference increased in all examined
      birth cohorts in both men (mean change 6.1 cm) and women (mean change 8.4 cm),
      but increased more markedly the younger the subjects were. The prevalence of
      abdominal obesity in men aged 25-34 increased from 5 % in 1994 to 31 % 13 years
      later. The prevalence of abdominal obesity more than doubled among both men and
      women. CONCLUSIONS: The increasing mean waist circumference is of concern. There
      is a need for further longitudinal studies of the changes in waist circumference.

PMID- 27688893
TI  - Recurrent anti-GBM disease with pulmonary artery aneurysms.
AB  - We present the first known case of pulmonary artery aneurysms as a feature of
      Recurrent Anti-Glomerular Basement Membrane disease. 

PMID- 27688894
TI  - Prevalence of malnutrition in hospitalised children: retrospective study in a
      Spanish tertiary-level hospital.
AB  - OBJECTIVE: To analyse the prevalence of malnutrition among paediatric patients at
      the time of hospital admission throughout a calendar year in a tertiary-level
      hospital and to identify those patients and/or groups of pathologies with a
      higher risk of malnutrition. DESIGN: Observational (retrospective evaluation of
      nutrition status). SETTING: Navarra Hospital Complex, Pamplona, Spain.
      PARTICIPANTS: A total of 852 patients hospitalised in 2013 in a Spanish tertiary
      level paediatric hospital (462 males and 390 females). MAIN OUTCOME MEASURES:
      Sex, age, body mass index at the moment of admission and days of hospitalisation
      and diagnosis codified according to the International Classification of Diseases
      were registered. RESULTS: The prevalence of malnutrition patients registered at
      the moment of admission was 8.2%. Diseases of the nervous system (22.9%),
      together with diseases of the respiratory system (22.9%), infectious diseases
      (18.6%), congenital malformations (11.4%) and diseases of the genitourinary
      system (8.6%) account for 84.4% of the cases with malnutrition. CONCLUSIONS: The
      overall prevalence rate for malnutrition in paediatric patients at the moment of
      admission in our hospital was 8.2%, being a figure similar to those published in
      occidental countries. It should be mandatory to accomplish an initial screening
      and follow-up during hospitalisation of younger patients and those suffering from
      diseases of the nervous and/or respiratory system and, especially, from
      congenital diseases.

PMID- 27688895
TI  - Fatal cerebral haemorrhage in a hypertensive seven-year-old boy.
AB  - A seven-year-old boy died from autopsy-proven brain haemorrhage due to
      hypertensive vasculopathy. This emphasizes the importance of early diagnosis and
      therapy of hypertension in children. Brain haemorrhage is a potentially fatal
      complication of paediatric hypertension. 

PMID- 27688896
TI  - Sodium glucose co-transporter 2 inhibitors in patients with resistant
      hypertension: a case study.
AB  - Sodium glucose co-transporter 2 inhibitors lower blood pressure by osmotic
      diuresis and can be considered in diabetic patients with resistant hypertension. 

PMID- 27688890
TI  - Biosynthesis and molecular actions of specialized 1,4-naphthoquinone natural
      products produced by horticultural plants.
AB  - The 1,4-naphthoquinones (1,4-NQs) are a diverse group of natural products found
      in every kingdom of life. Plants, including many horticultural species,
      collectively synthesize hundreds of specialized 1,4-NQs with ecological roles in
      plant-plant (allelopathy), plant-insect and plant-microbe interactions. Numerous
      horticultural plants producing 1,4-NQs have also served as sources of traditional
      medicines for hundreds of years. As a result, horticultural species have been at
      the forefront of many basic studies conducted to understand the metabolism and
      function of specialized plant 1,4-NQs. Several 1,4-NQ natural products derived
      from horticultural plants have also emerged as promising scaffolds for developing
      new drugs. In this review, the current understanding of the core metabolic
      pathways leading to plant 1,4-NQs is provided with additional emphasis on
      downstream natural products originating from horticultural species. An overview
      on the biochemical mechanisms of action, both from an ecological and
      pharmacological perspective, of 1,4-NQs derived from horticultural plants is also
      provided. In addition, future directions for improving basic knowledge about
      plant 1,4-NQ metabolism are discussed. 

PMID- 27688897
TI  - Cardiac sarcoma presenting with abdominal pain and mimicking myxoma on
      echocardiogram.
AB  - Cardiac sarcoma's are highly aggressive tumours. Clear resection margins +/-
      autotransplant, followed by chemotherapy, offers the best survival chance.
      Therefore, frozen section should be preformed when there is ambiguity in
      diagnosis. 

PMID- 27688898
TI  - Discussing sudden unexpected death in epilepsy: Are we empowering our patients? A
      questionnaire survey.
AB  - OBJECTIVE: To examine patient knowledge about sudden unexpected death in epilepsy
      (SUDEP) compared to other risks in epilepsy. To explore patients' experiences
      surrounding SUDEP disclosure and opinions on how information should be delivered.
      DESIGN: A cross-sectional questionnaire. SETTING: Royal Free Hospital, London
      outpatient epilepsy clinics. PARTICIPANTS: New and follow-up patients attending
      epilepsy clinics at a London teaching hospital over six months. Patients
      identified as being at risk of suffering negative emotional or psychological
      consequences of SUDEP discussions were excluded. MAIN OUTCOME MEASURES: Patient
      knowledge about epilepsy risks; patient opinion regarding source, timing and
      delivery of SUDEP information; impact on health seeking behaviour. RESULTS:
      Ninety-eight per cent of patients were aware of medication adherence, 84% of
      factors influencing seizure frequency, 78% of driving regulations, 50% of SUDEP
      and 38% of status epilepticus; 72% of patients felt that SUDEP information should
      be given to all patients. Preferences for timing of SUDEP discussions varied
      between those wanting information at diagnosis (40%) and those preferring to
      receive it after three clinic appointments (18%) to avoid information overload at
      the first consultation. Emotional responses (48% positive, 38% negative)
      predominated over measurable behavioural change following SUDEP discussions.
      CONCLUSIONS: Less than half the patients knew about SUDEP and status epilepticus.
      Although the majority of patients with epilepsy wish to be informed about SUDEP
      early on in their diagnosis, information must be delivered in a way that promotes
      patient knowledge and empowerment.

PMID- 27688899
TI  - Patterns and trends in mortality among HIV-infected and HIV-uninfected patients
      in a major Internal Medicine Unit in Yaounde, Cameroon: a retrospective cohort
      study.
AB  - OBJECTIVE: To describe the trends in mortality and the spectrum of disease in HIV
      infected and -uninfected inpatients in a population in Yaounde. DESIGN: A
      retrospective study. SETTING: Internal Medicine Unit, University Hospital Centre,
      Yaounde, Cameroon. PARTICIPANTS: All deaths registered between January 2000 and
      May 2007 in the unit. MAIN OUTCOMES MEASURES: Sociodemographic characteristics,
      clinical features and results of all investigations done, cause of death.
      RESULTS: During the study period, 362 deaths were registered, consisting of 281
      (77.6%) in HIV-infected patients, 54.4% of which were women. HIV-infected
      patients were younger (mean age: 40.2 (SD: 11.6) vs. 55.5 (SD: 18.3) years, p <
      0.001) and economically active (60.3% vs. 24.4%, p < 0.001). Most HIV-infected
      patients (77.6%) were classified as WHO stage IV, with the rest being WHO stage
      III. Most HIV-infected patients (87.8%) had evidence of profound
      immunosuppression (CD4 < 200 cells/mm(3)). The mortality trend appeared to be
      declining with appropriate interventions. The most frequent causes of death in
      HIV-infected patients were pleural/pulmonary tuberculosis (34.2%), undefined
      meningoencephalitis (20.3%), other pneumonias (18.2%), toxoplasmosis (16.4%),
      cryptococcal meningitis (14.2%) and Kaposi sarcoma (15.7%). HIV-uninfected
      patients died mostly as a result of chronic diseases including liver diseases
      (17.3%), kidney failure (13.6%), congestive heart failure (11.1%) and stroke
      (9.9%). CONCLUSION: There was a declining mortality due to HIV with appropriate
      interventions such as subsidised tests for HIV-infected patients, increased
      availability of HAART and other medications for prevention and treatment of
      opportunistic infections. The spectrum of HIV disease was wide and preventable.

PMID- 27688900
TI  - Plasma tenofovir trough concentrations are associated with renal dysfunction in
      Japanese patients with HIV infection: a retrospective cohort study.
AB  - BACKGROUND: Plasma tenofovir (TFV) trough concentrations may be relevant for
      tenofovir disoproxil fumarate (TDF)-induced renal dysfunction. The purpose of
      this study was to determine the association between plasma TFV trough
      concentrations and TDF-induced renal dysfunction in Japanese patients with human
      immunodeficiency virus (HIV) infection. METHODS: A 48-week, retrospective cohort
      study was performed with Japanese patients with HIV infection who started a TDF
      containing combination antiretroviral therapy regimen. Plasma TFV trough
      concentrations were obtained at steady state. The following variables were
      included in the analysis: sex, age, body weight, body mass index (BMI), serum
      creatinine, CD4+ cell count, HIV-RNA, concomitant medications, comorbidities,
      plasma TFV trough concentrations, and estimated glomerular filtration rate
      (eGFR). For comparisons of variables, we used Mann-Whitney U tests or Fisher's
      exact tests. Then, variables associated with renal dysfunction in the univariate
      analysis were entered into correlation analysis. RESULTS: The analysis included
      11 patients. The rate of decrease in eGFR was significantly correlated with body
      weight (Spearman correlation = -0.645, p = 0.041), BMI (Spearman correlation = 
      0.682, p = 0.031), and plasma TFV trough concentrations (Spearman correlation =
      0.709, p = 0.025). CONCLUSIONS: Despite the small sample size, our findings
      suggest that higher plasma TFV trough concentrations may cause TDF-induced renal
      dysfunction. To prevent TDF-induced renal dysfunction, we propose that individual
      monitoring of plasma TFV trough concentrations should be performed in Japanese
      patients with HIV infection.

PMID- 27688902
TI  - Neuromuscular study of early branching Diuronotus aspetos (Paucitubulatina)
      yields insights into the evolution of organs systems in Gastrotricha.
AB  - BACKGROUND: Diuronotus is one of the most recently described genera of
      Paucitubulatina, one of the three major clades in Gastrotricha. Its morphology
      suggests that Diuronotus is an early branch of Paucitubulatina, making it a key
      taxon for understanding the evolution of this morphologically understudied group.
      Here we test its phylogenetic position employing molecular data, and provide
      detailed descriptions of the muscular, nervous, and ciliary systems of Diuronotus
      aspetos, using immunohistochemistry and confocal laser scanning microscopy.
      RESULTS: We confirm the proposed position of D. aspetos within Muselliferidae,
      and find this family to be the sister group to Xenotrichulidae. The muscular
      system, revealed by F-actin staining, shows a simple, but unique organization of
      the trunk musculature with a reduction to three pairs of longitudinal muscles and
      addition of up to five pairs of dorso-ventral muscles, versus the six
      longitudinal and two dorso-ventral pairs found in most Paucitubulatina. Using
      acetylated alpha-tubulin immunoreactivity, we describe the pharynx in detail,
      including new nervous structures, two pairs of sensory cilia, and a unique canal
      system. The central nervous system, as revealed by immunohistochemistry, shows
      the general pattern of Gastrotricha having a bilobed brain and a pair of ventro
      longitudinal nerve cords. However, in addition are found an anterior nerve ring,
      several anterior longitudinal nerves, and four ventral commissures (pharyngeal,
      trunk, pre-anal, and terminal). Two pairs of protonephridia are documented, while
      other Paucitubulatina have one. Moreover, the precise arrangement of
      multiciliated cells is unraveled, yielding a pattern of possibly systematic
      importance. CONCLUSION: Several neural structures of Diuronotus resemble those
      found in Xenotrichula (Xenotrichulidae) and may constitute new apomorphies of
      Paucitubulatina, or even Gastrotricha. In order to test these new evolutionary
      hypotheses, comparable morphological data from other understudied gastrotrich
      branches and a better resolution of the basal nodes of the gastrotrich phylogeny
      are warranted. Nonetheless, the present study offers new insights into the
      evolution of organ systems and systematic importance of so-far neglected
      characters in Gastrotricha.

PMID- 27688901
TI  - Correlation between blood magnesium and calcium concentration in patients treated
      with an anti-EGFR antibody.
AB  - BACKGROUND: Hypomagnesemia is one of the characteristic side effects of the human
      anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, cetuximab and
      panitumumab. The major mechanism of anti-EGFR antibody-related hypomagnesemia is
      suppression of EGFR-mediated urinary Mg(2+) reabsorption in both the renal tubule
      the intestinal tract. Since Mg(2+) is known to affect blood Ca(2+) levels through
      regulation of parathyroid hormone (PTH) secretion, we investigated the
      correlation between Ca(2+) and Mg(2+) concentration in blood. METHODS: Between
      April 2012 and October 2015, blood Mg(2+) and Ca(2+) concentrations (albumin
      corrected value) of 22 colon cancer patients undergoing treatment with either
      cetuximab or panitumumab at Toyooka Public Hospital were measured simultaneously.
      RESULTS: Hypomagnesemia (of all Grades) was reported in 13 of 22 patients. Two
      patients had hypomagnesemia of severity > Grade 3. Changes in blood Mg(2+) and
      Ca(2+) concentration showed a significant correlation (r(2) = 0.7455), which
      could be expressed using the following equation, Ca(2+) concentration = 1.4268 *
      (Mg(2+) concentration) + 7.1126. CONCLUSION: Since the early stages of
      hypomagnesemia produce no characteristic clinical symptoms, it is easily
      overlooked until it becomes severe. The investigation results suggest that if low
      blood Ca(2+) concentration (mg/dL) is observed in patients administered anti-EGFR
      antibodies, early evaluation of blood Mg(2+) concentration (mg/dL) and prompt
      supportive care are required to prevent aggravation of hypomagnesemia.

PMID- 27688903
TI  - CRISPR, a Crossroads in Genetic Intervention: Pitting the Right to Health against
      the Right to Disability.
AB  - Reproductive genetic technologies (RGTs), including gene-editing technology, are
      being discovered and refined at an exponential pace. One gene-editing innovation
      that demands our swift attention is CRISPR/Cas9, a system of clustered regularly
      interspaced short palindromic repeats and a protein called Cas9. As CRISPR and
      other RGTs continue being developed, we must remain vigilant concerning the
      potential implications of genetic-engineering technology on our interpersonal and
      legal relationships. In the face of increasingly numerous and refined RGTs, we
      must maintain the rights of everyone: potential parents, prospective children,
      and individuals (both living and prospective) with disabilities. For those who
      wish to become parents, how should procreation be regulated in light of
      developing RGTs, especially gene-editing technology? What duties do parents owe
      their children, and when does such a duty attach? What role should RGTs play in
      parents' fulfillment of their duties to their children? This article will
      contextualize the right to health and what I will term the "right to disability"
      in the CRISPR/Cas9 landscape. The article will then explore these rights in
      reference to the "subjunctive-threshold" interpretation of harm. Finally, I will
      argue that RGTs must be thoughtfully regulated, with such regulations taking into
      account the opinions of geneticists, bioethicists, and lay people concerning both
      the right to health and the right to disability.

PMID- 27688904
TI  - C1Q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal
      Transplant Candidates with Donor-Specific Antibodies: High Specificity but Low
      Sensitivity When Predicting Flow Crossmatch.
AB  - The aim of the present study was to describe the association of positive flow
      cross match (FXM) and C1q-SAB. Methods. In this observational, cross-sectional,
      and comparative study, patients included had negative AHG-CDC-XM and donor
      specific antibodies (DSA) and were tested with FXM. All pretransplant sera were
      tested with C1q-SAB assay. Results. A total of 50 donor/recipient evaluations
      were conducted; half of them had at least one C1q+ Ab (n = 26, 52%). Ten patients
      (20.0%) had DSA C1q+ Ab. Twenty-five (50%) FXMs were positive. Factors associated
      with a positive FXM were the presence of C1q+ Ab (DSA C1q+ Ab: OR 27, 2.80
      259.56, P = 0.004, and no DSA C1q+ Ab: OR 5, 1.27-19.68, P = 0.021) and the DSA
      LABScreen-SAB MFI (OR 1.26, 95% CI 1.06-1.49, P = 0.007). The cutoff point of
      immunodominant LABScreen SAB DSA-MFI with the greatest sensitivity and
      specificity to predict FXM was 2,300 (sensitivity: 72% and specificity: 75%). For
      FXM prediction, DSA C1q+ Ab was the most specific (95.8%, 85-100) and the
      combination of DSA-MFI > 2,300 and C1q+ Ab was the most sensitive (92.0%, 79.3
      100). Conclusions. C1q+ Ab and LABScreen SAB DSA-MFI were significantly
      associated with FXM. DSA C1q+ Ab was highly specific but with low sensitivity. 

PMID- 27688905
TI  - Impact of Recipient and Donor Obesity Match on the Outcomes of Liver
      Transplantation: All Matches Are Not Perfect.
AB  - There is a paucity of literature examining recipient-donor obesity matching on
      liver transplantation outcomes. The United Network for Organ Sharing database was
      queried for first-time recipients of liver transplant whose age was >=18 between
      January 2003 and September 2013. Outcomes including patient and graft survival at
      30 days, 1 year, and 5 years and overall, liver retransplantation, and length of
      stay were compared between nonobese recipients receiving a graft from nonobese
      donors and obese recipient-obese donor, obese recipient-nonobese donor, and
      nonobese recipient-obese donor pairs. 51,556 LT recipients were identified,
      including 34,217 (66%) nonobese and 17,339 (34%) obese recipients. The
      proportions of patients receiving an allograft from an obese donor were 24% and
      29%, respectively, among nonobese and obese recipients. Graft loss (HR: 1.27; 95%
      CI: 1.09-1.46; p = 0.002) and mortality (HR: 1.38; 95% CI: 1.16-1.65; p < 0.001)
      at 30 days were increased in the obese recipient-obese donor pair. However, 1
      year graft (HR: 0.83; 95% CI: 0.74-0.93; p = 0.002) and patient (HR: 0.84; 95%
      CI: 0.74-0.95; p = 0.007) survival and overall patient (HR: 0.93; 95% CI: 0.86
      1.00; p = 0.042) survival were favorable. There is evidence of recipient and
      donor obesity disadvantage early, but survival curves demonstrate improved long
      term outcomes. It is important to consider obesity in the donor-recipient match. 

PMID- 27688906
TI  - The Intoxication Effects of Methanol and Formic Acid on Rat Retina Function.
AB  - Objective. To explore the potential effects of methanol and its metabolite,
      formic acid, on rat retina function. Methods. Sprague-Dawley rats were divided
      into 3- and 7-day groups and a control. Experimental groups were given methanol
      and the control group were provided saline by gavage. Retinal function of each
      group was assessed by electroretinogram. Concentrations of methanol and formic
      acid were detected by GC/HS and HPLC, respectively. Results. The a and b
      amplitudes of methanol treated groups decreased and latent periods delayed in
      scotopic and photopic ERG recordings. The summed amplitudes of oscillatory
      potentials (OPs) of groups B and C decreased and the elapsed time delayed. The
      amplitudes of OS1, OS3, OS4, and OS5 of group B and OS3, OS4, and OS5 of group C
      decreased compared with the control group. The IPI1 of group B and IPI1-4 of
      group C were broader compared with the control group and the IPI1-4 and ET of
      group B were broader than group C. CONCLUSIONS: Both of scotopic and photopic
      retinal functions were impaired by methanol poisoning, and impairment was more
      serious in the 7-day than in the 3-day group. OPs, especially later OPs and IPI2,
      were more sensitive to methanol intoxication than other eletroretinogram
      subcomponents.

PMID- 27688907
TI  - Scleral Buckling for Rhegmatogenous Retinal Detachment Associated with Pars
      Planitis.
AB  - Purpose. To evaluate the surgical outcome of scleral buckling (SB) in
      rhegmatogenous retinal detachment (RRD) patients associated with pars planitis.
      Methods. Retrospective review of RRD patients (32 eyes of pars planitis RRD and
      180 eyes of primary RRD) who underwent SB. We compared primary and final
      anatomical success rates and visual outcomes between two groups. Results. Primary
      and final anatomical success were achieved in 25 (78.1%) and 31 (96.8%) eyes in
      the pars planitis RRD group and in 167 eyes (92.7%) and 176 eyes (97.7%) in
      primary RRD group, respectively. Both groups showed significant visual
      improvement (p < 0.001) and there were no significant differences in final visual
      acuity. Pars planitis RRD group was associated with higher rate of postoperative
      proliferative vitreoretinopathy (PVR) development (12.5% versus 2.8%, p = 0.031).
      Pars planitis and high myopia were significant preoperative risk factors and
      pseudophakia was borderline risk for primary anatomical failure after adjusting
      for various clinical factors. Conclusions. Pars planitis associated RRD showed
      inferior primary anatomical outcome after SB due to postoperative PVR
      development. However, final anatomical and visual outcomes were favorable. RRD
      cases associated with pars planitis, high myopia, and pseudophakia might benefit
      from different surgical approaches, such as combined vitrectomy and SB. 

PMID- 27688909
TI  - Comment on "Evaluation of Subfoveal Choroidal Thickness in Internal Carotid
      Artery Stenosis".

PMID- 27688908
TI  - Corneal Biomechanical Findings in Contact Lens Induced Corneal Warpage.
AB  - Purpose. To evaluate the difference in biomechanical properties between contact
      lens induced corneal warpage and normal and keratoconic eyes. Method. Prospective
      observational case control study, where 94 eyes of 47 warpage suspicious and 46
      eyes of 23 keratoconic patients were included. Warpage suspected cases were
      followed until a definite diagnosis was made (warpage, normal, or keratoconus).
      Results. 44 eyes of 22 patients had contact lens related corneal warpage. 46 eyes
      of 23 people were diagnosed as nonwarpage normal eyes. 46 eyes of 23 known
      keratoconus patients were included for comparison. The mean age of the
      participants was 23.8 +/- 3.8 years, and 66.2% of the subjects were female. The
      demographic and refractive data were not different between warpage and normal
      groups but were different in the keratoconus group. The biomechanical properties
      (corneal hysteresis or CH and corneal resistance factor or CRF) were different
      with the highest value in the warpage group followed by normal and keratoconus
      groups. CRF was 10.08 +/- 1.75, 9.23 +/- 1.22, and 7.38 +/- 2.14 and CH was 10.21
      +/- 1.57, 9.59 +/- 1.21, and 8.69 +/- 2.34 in the warpage, normal, and
      keratoconus groups, respectively. Conclusion. Corneal biomechanics may be
      different in people who develop contact lens induced warpage. 

PMID- 27688910
TI  - Evaluation of Anterior Chamber Volume in Cataract Patients with Swept-Source
      Optical Coherence Tomography.
AB  - Purpose. To evaluate the anterior chamber volume in cataract patients with Swept
      Source Optical Coherence Tomography (SS-OCT) and its influencing factors.
      Methods. Anterior chamber volume of 92 cataract patients was evaluated with SS
      OCT in this cross-sectional study. Univariate analyses and multiple linear
      regression were used to investigate gender, age, operated eye, posterior vitreous
      detachment, lens opacity grading, and axial length (AXL) related variables
      capable of influencing the ACV. Results. The average ACV was 139.80 +/- 38.21
      mm(3) (range 59.41 to 254.09 mm(3)). The average ACV was significantly larger in
      male patients than in female patients (P = 0.001). ACV was negatively correlated
      with age and LOCS III cortical (C) grading of the lens (Pearson's correlation
      analysis, r = -0.443, P < 0.001, and Spearman's correlation analysis, rho = 
      0.450, P < 0.001). ACV was also increased with AXL (Pearson's correlation
      analysis, r = 0.552, P < 0.001). Multiple linear regression showed that, with all
      of the covariates entered into the model, gender (P = 0.002), age (P = 0.015),
      LOCS III C grade (P = 0.043), and AXL (P = 0.001) were still associated with ACV
      (F = 10.252  P < 0.001  R (2) = 0.498). Conclusion. With SS-OCT, we found that,
      in healthy cataract patients, ACV varied significantly among different subjects.
      Influencing factors that contribute to reduced ACV were female gender, increased
      age, LOCS III C grade, and shorter AXL. 

PMID- 27688911
TI  - Can Transcutaneous CO2 Tension Be Used to Calculate Ventilatory Dead Space? A
      Pilot Study.
AB  - Dead space fraction (V d/V t) measurement performed using volumetric capnography
      requires arterial blood gas (ABG) sampling to estimate the partial pressure of
      carbon dioxide (PaCO2). In recent years, transcutaneous capnography (PtcCO2) has
      emerged as a noninvasive method of estimating PaCO2. We hypothesized that PtcCO2
      can be used as a substitute for PaCO2 in the calculation of V d/V t. In this
      prospective pilot comparison study, 30 consecutive postcardiac surgery
      mechanically ventilated patients had V d/V t calculated separately using
      volumetric capnography by substituting PtcCO2 for PaCO2. The mean V d/V t
      calculated using PaCO2 and PtcCO2 was 0.48 +/- 0.09 and 0.53 +/- 0.08,
      respectively, with a strong positive correlation between the two methods of
      calculation (Pearson's correlation = 0.87, p < 0.05). Bland-Altman analysis
      showed a mean difference of -0.05 (95% CI: -0.01 to -0.09) between the two
      methods. PtcCO2 measurements can provide a noninvasive means to measure V d/V t,
      thus accessing important physiologic information and prognostic assessment in
      patients receiving mechanical ventilation. 

PMID- 27688912
TI  - Comparative Proteomic Analysis of Differential Proteins in Response to Aqueous
      Extract of Quercus infectoria Gall in Methicillin-Resistant Staphylococcus
      aureus.
AB  - The aim of this study is to analyze the differential proteins in MRSA ATCC 33591
      treated with aqueous extract from Q. infectoria gall. Protein extracts were
      obtained from MRSA cells by sonication and were separated by 2D polyacrylamide
      gels. Protein spots of interest were extracted from the gels and identified using
      LC-ESI-QTOF MS. The concentration of Q. infectoria extract used for 2D-gel
      electrophoresis was subinhibitory concentration. Minimum inhibitory concentration
      (MIC) value of the extract against MRSA was 19.50 MUg/mL with bacteriostatic
      action at 1x MIC from time-kill assay. However, the extract exhibited dose
      dependent manner and was bactericidal at 4x MIC with more than 3 log10 CFU/mL
      reduction at 4 h. 2D-GE map showed that 18 protein spots were upregulated and
      another six were downregulated more than twofold (p < 0.05) after treatment with
      subinhibitory concentration. Out of six proteins being downregulated, four
      proteins were identified as ferritin and catalase, branched-chain alpha-keto acid
      dehydrogenase subunit E2, and succinyl-CoA ligase [ADP-forming] subunit beta.
      Seven upregulated proteins which have been successfully identified were 3
      hydroxyacyl-CoA dehydrogenase, NAD binding domain protein, formate C
      acetyltransferase, 3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ, NAD
      dependent epimerase/dehydratase family protein, and phosphopantothenoyl cysteine
      decarboxylase. It is postulated that the main mechanism of aqueous extract from
      gall of Q. infectoria was most likely involved in energy metabolism and protein
      stress. 

PMID- 27688913
TI  - Predictors of Gestational Weight Gain among White and Latina Women and
      Associations with Birth Weight.
AB  - This study examined racial/ethnic differences in gestational weight gain (GWG)
      predictors and association of first-trimester GWG to overall GWG among 271 White
      women and 300 Latina women. Rates of within-guideline GWG were higher among
      Latinas than among Whites (28.7% versus 24.4%, p < 0.016). Adjusted odds of above
      guideline GWG were higher among prepregnancy overweight (OR = 3.4, CI = 1.8-6.5)
      and obese (OR = 4.5, CI = 2.3-9.0) women than among healthy weight women and
      among women with above-guideline first-trimester GWG than among those with within
      guideline first-trimester GWG (OR = 4.9, CI = 2.8-8.8). GWG was positively
      associated with neonate birth size (p < 0.001). Interventions targeting
      prepregnancy overweight or obese women and those with excessive first-trimester
      GWG are needed.

PMID- 27688914
TI  - The Prevalence of MRSA Nasal Carriage in Preoperative Pediatric Orthopaedic
      Patients.
AB  - Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) has been
      described as a risk factor for postsurgical infection. The purpose of this study
      is to determine the prevalence of MRSA in pediatric orthopaedic patients and
      whether being a MRSA carrier is a predictor of postoperative infection. Six
      hundred and ninety-nine consecutive pediatric patients who underwent MRSA nasal
      screening prior to surgery were studied. Postoperative cultures, total surgical
      site infections (SSIs), and epidemiological and surgical prophylaxis data were
      reviewed. Forty-four of 699 patients (6.29%) screened positive for MRSA. Nine of
      the 44 patients (20.5%) that screened positive for MRSA had a subsequent SSI
      compared to 10 of the 655 patients (1.52%) that screened negative (p < 0.05). All
      9 patients with a SSI had myelomeningocele. The prevalence of MRSA was 6.30% and
      was predictive of postoperative infection. Children with myelomeningocele were at
      the highest risk for having a positive MRSA screening and developing SSI. 

PMID- 27688916
TI  - Comment on "A Rare Case of Renal Infarct due to Noncompaction Cardiomyopathy: A
      Case Report and Literature Review".

PMID- 27688915
TI  - Wnt5a Increases the Glycolytic Rate and the Activity of the Pentose Phosphate
      Pathway in Cortical Neurons.
AB  - In the last few years, several reports have proposed that Wnt signaling is a
      general metabolic regulator, suggesting a role for this pathway in the control of
      metabolic flux. Wnt signaling is critical for several neuronal functions, but
      little is known about the correlation between this pathway and energy metabolism.
      The brain has a high demand for glucose, which is mainly used for energy
      production. Neurons use energy for highly specific processes that require a high
      energy level, such as maintaining the electrical potential and synthesizing
      neurotransmitters. Moreover, an important metabolic impairment has been described
      in all neurodegenerative disorders. Despite the key role of glucose metabolism in
      the brain, little is known about the cellular pathways involved in regulating
      this process. We report here that Wnt5a induces an increase in glucose uptake and
      glycolytic rate and an increase in the activity of the pentose phosphate pathway;
      the effects of Wnt5a require the intracellular generation of nitric oxide. Our
      data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect
      that could be important for the reported neuroprotective role of Wnt signaling in
      neurodegenerative disorders.

PMID- 27688917
TI  - Compartment Syndrome as a Result of Systemic Capillary Leak Syndrome.
AB  - Objective. To describe a single case of Systemic Capillary Leak Syndrome (SCLS)
      with a rare complication of compartment syndrome. Patient. Our patient is a 57
      year-old male, referred to our hospital due to polycythemia (hemoglobin (Hgb) of
      220 g/L), hypotension, acute renal failure, and bilateral calf pain. Measurements
      and Main Results. The patient required bilateral forearm, thigh, and calf
      fasciotomies during his ICU stay and continuous renal replacement therapy was
      instituted following onset of acute renal failure and oliguria. Ongoing
      hemodynamic (Norepinephrine and Milrinone infusion) and respiratory (ventilator)
      support in the ICU was provided until resolution of intravascular fluid
      extravasation. Conclusions. SCLS is an extremely rare disorder characterized by
      unexplained episodic capillary hyperpermeability, which causes shift of volume
      and protein from the intravascular space to the interstitial space. Patients
      present with significant hypotension, hemoconcentration, hypovolemia, and
      oliguria. Severe edema results from leakage of fluid and proteins into tissue.
      The most important part of treatment is maintaining stable hemodynamics, ruling
      out other causes of shock and diligent monitoring for complications. Awareness of
      the clinical syndrome with the rare complication of compartment syndrome may help
      guide investigations and diagnoses of these critically ill patients. 

PMID- 27688918
TI  - Rapidly Progressive Spontaneous Spinal Epidural Abscess.
AB  - Spinal epidural abscess (SEA) is a rare disease which is often rapidly
      progressive. Delayed diagnosis of SEA may lead to serious complications and the
      clinical findings of SEA are generally nonspecific. Paraspinal abscess should be
      considered in the presence of local low back tenderness, redness, and pain with
      fever, particularly in children. In case of delayed diagnosis and treatment, SEA
      may spread to the epidural space and may cause neurological deficits. Magnetic
      resonance imaging (MRI) remains the method of choice in the diagnosis of SEA.
      Treatment of SEA often consists of both medical and surgical therapy including
      drainage with percutaneous entry, corpectomy, and instrumentation. 

PMID- 27688919
TI  - Parkinson's Disease and Cryptogenic Epilepsy.
AB  - Epilepsy is an uncommon comorbidity of Parkinson's disease (PD) and has been
      considered not directly associated with PD. We present five patients (3 men and 2
      women; ages 49-85) who had concomitant PD and cryptogenic epilepsy. Although
      rare, epilepsy can coexist with PD and their coexistence may influence the
      progression of PD. While this may be a chance association, an evolving
      understanding of the neurophysiological basis of either disease may suggest a
      mechanistic association. 

PMID- 27688920
TI  - Chemotherapy Used to Halt Lower GI Bleeding in a Rare Case of Metastatic
      Choriocarcinoma to the GI Tract.
AB  - Choriocarcinoma, a nonseminomatous germ cell tumor, is a rare type of testicular
      malignancy that tends to occur in young males. It is, however, exceedingly rare
      for choriocarcinoma to involve the GI tract. In this article, we present a rare
      case of a 31-year-old male, diagnosed with choriocarcinoma of the left testes,
      along with several metastases to distant sites. The patient presented with
      headaches and severe lower GI bleeding due to metastases to the GI tract, which
      was eventually controlled with systemic chemotherapy, while requiring several
      units of packed RBCs during his admission to the hospital. An extensive
      literature review found very few cases of the occurrence of GI bleeding as a
      consequence of choriocarcinoma due to metastases to the GI tract. 

PMID- 27688921
TI  - Management of Ankyloglossia and Breastfeeding Difficulties in the Newborn:
      Breastfeeding Sessions, Myofunctional Therapy, and Frenotomy.
AB  - The problems of suction in newborns give rise to multiple consequences for both
      the mother and the newborn. The objective of this paper is to present a case of
      ankyloglossia ("tongue-tie") and the suction problems that were treated by a
      multidisciplinary team. The subject is a 17-day-old male patient, with
      ankyloglossia and suction problems during breastfeeding (pain in the
      breastfeeding mother, poor weight gain, and long breastfeeds). The patient
      followed the circuit established in our centre between the services of Oral and
      Maxillofacial Surgery and Breastfeeding and Speech Therapy and Orofacial
      Rehabilitation (CELERE). The evolution following the breastfeeding sessions, the
      myofunctional stimulation, and the lingual frenotomy was very favourable, thereby
      solving the suction problems that the newborn presented. All our patients receive
      breastfeeding sessions and myofunctional therapy as treatment. We know that a
      frenotomy is not always necessary and we believe that the stimulation of sucking
      before and after the surgical intervention is important in order to improve the
      final result.

PMID- 27688922
TI  - Delirious Mania Associated with Autoimmune Gastrothyroidal Syndrome of a Mid-Life
      Female: The Role of Hashimoto Encephalopathy and a 3-Year Follow-Up including
      Serum Autoantibody Levels.
AB  - We report the case study of a 57-year-old Caucasian female with steroid
      responsive encephalopathy associated with autoimmune thyroiditis (SREAT),
      commonly termed Hashimoto encephalopathy (HE). This presentation includes one of
      the longest lasting follow-up studies of HE considering the neuropsychiatric
      symptoms (here delirium, mania, and EEG-slowing) and their relation to serum
      autoantibody levels. Antithyroid-peroxidase autoantibodies, the hallmark of
      autoimmune thyroiditis, were found in the serum and also in the cerebrospinal
      fluid. Diagnostic analyses found no evidence of limbic encephalopathies
      characterized by serum antibodies against intracellular, synaptic, or further
      cell surface antigenic targets, neoplasm, and connective tissue or vasculitis
      diseases. A potential contribution of bipolar disorder and metabolic
      encephalopathies due to severe hypothyroidism, glucocorticoid treatment,
      accelerated thyroid hormone replacement therapy, or vitamin B deficiency is
      critically discussed. Another special feature of this case report is the linkage
      of HE to an autoimmune polyendocrine syndrome (type 3B) affecting the
      gastroduodenum in addition to the thyroid gland. 

PMID- 27688924
TI  - Ischemic Strokes: Observations from a Hospital Based Stroke Registry in
      Bangladesh.
AB  - Background. Stroke is an important morbidity for low and middle income countries
      like Bangladesh. We established the first stroke registry in Bangladesh. Methods.
      Data was collected from stroke patients who were admitted in Department of
      Neurology of BIRDEM with first ever stroke, aged between 30 and 90 years.
      Patients with intracerebral hemorrhage, subarachnoid and subdural hemorrhage, and
      posttrauma features were excluded. Results. Data was gathered from 679 stroke
      patients. Mean age was 60.6 years. Almost 68% of patients were male. Small vessel
      strokes were the most common accounting for 45.4% of all the patients followed by
      large vessel getting affected in 32.5% of the cases. Only 16 (2.4%) died during
      treatment, and 436 (64.2%) patients had their mRS score of 3 to 5. Age greater
      than 70 years was associated with poor outcome on discharge [OR 1.79 (95% CI:
      1.05 to 3.06)] adjusting for gender, duration of hospital stay, HDL, and
      pneumonia. Age, mRS, systolic blood pressure, urinary tract infection, pneumonia,
      and stroke severity explained the Barthel score. Conclusion. Mortality was low
      but most of patient had moderate to severe disability at discharge. Age, mRS,
      systolic blood pressure, urinary tract infection, pneumonia, and stroke severity
      influenced the Barthel score. 

PMID- 27688925
TI  - Direct Comparison of (19)F qNMR and (1)H qNMR by Characterizing Atorvastatin
      Calcium Content.
AB  - Quantitative nuclear magnetic resonance (qNMR) is a powerful tool in measuring
      drug content because of its high speed, sensitivity, and precision. Most of the
      reports were based on proton qNMR ((1)H qNMR) and only a few fluorine qNMR ((19)F
      qNMR) were reported. No research has been conducted to directly compare the
      advantage and disadvantage between these two methods. In the present study, both
      (19)F and (1)H qNMR were performed to characterize the content of atorvastatin
      calcium with the same internal standard. Linearity, precision, and results from
      two methods were compared. Results showed that (19)F qNMR has similar precision
      and sensitivity to (1)H qNMR. Both methods generate similar results compared to
      mass balance method. Major advantage from (19)F qNMR is that the analyte signal
      is with less or no interference from impurities. (19)F qNMR is an excellent
      approach to quantify fluorine-containing analytes. 

PMID- 27688923
TI  - Cognitive Training in Parkinson's Disease: A Review of Studies from 2000 to 2014.
AB  - Cognitive deficits are prevalent among patients with Parkinson's disease (PD), in
      both early and late stages of the disease. These deficits are associated with
      lower quality of life, loss of independence, and institutionalization. To date,
      there is no effective pharmacological treatment for the range of cognitive
      impairments presented in PD. Cognitive training (CT) has been explored as an
      alternative approach to remediating cognition in PD. In this review we present a
      detailed summary of 13 studies of CT that have been conducted between 2000 and
      2014 and a critical examination of the evidence for the effectiveness and
      applicability of CT in PD. Although the evidence shows that CT leads to short
      term, moderate improvements in some cognitive functions, methodological
      inconsistencies weaken these results. We discuss several key limitations of the
      literature to date, propose methods of addressing these questions, and outline
      the future directions that studies of CT in PD should pursue. Studies need to
      provide more detail about the cognitive profile of participants, include larger
      sample sizes, be hypothesis driven, and be clearer about the training
      interventions and the outcome measures. 

PMID- 27688926
TI  - The coming paradigm shift: A transition from manual to automated microscopy.
AB  - The field of pathology has used light microscopy (LM) extensively since the mid
      19(th) century for examination of histological tissue preparations. This
      technology has remained the foremost tool in use by pathologists even as other
      fields have undergone a great change in recent years through new technologies.
      However, as new microscopy techniques are perfected and made available, this
      reliance on the standard LM will likely begin to change. Advanced imaging
      involving both diffraction-limited and subdiffraction techniques are bringing
      nondestructive, high-resolution, molecular-level imaging to pathology. Some of
      these technologies can produce three-dimensional (3D) datasets from sampled
      tissues. In addition, block-face/tissue-sectioning techniques are already
      providing automated, large-scale 3D datasets of whole specimens. These datasets
      allow pathologists to see an entire sample with all of its spatial information
      intact, and furthermore allow image analysis such as detection, segmentation, and
      classification, which are impossible in standard LM. It is likely that these
      technologies herald a major paradigm shift in the field of pathology. 

PMID- 27688927
TI  - A novel method for morphological pleomorphism and heterogeneity quantitative
      measurement: Named cell feature level co-occurrence matrix.
AB  - BACKGROUND: Recent developments in molecular pathology and genetic/epigenetic
      analysis of cancer tissue have resulted in a marked increase in objective and
      measurable data. In comparison, the traditional morphological analysis approach
      to pathology diagnosis, which can connect these molecular data and clinical
      diagnosis, is still mostly subjective. Even though the advent and popularization
      of digital pathology has provided a boost to computer-aided diagnosis, some
      important pathological concepts still remain largely non-quantitative and their
      associated data measurements depend on the pathologist's sense and experience.
      Such features include pleomorphism and heterogeneity. METHODS AND RESULTS: In
      this paper, we propose a method for the objective measurement of pleomorphism and
      heterogeneity, using the cell-level co-occurrence matrix. Our method is based on
      the widely used Gray-level co-occurrence matrix (GLCM), where relations between
      neighboring pixel intensity levels are captured into a co-occurrence matrix,
      followed by the application of analysis functions such as Haralick features. In
      the pathological tissue image, through image processing techniques, each nucleus
      can be measured and each nucleus has its own measureable features like nucleus
      size, roundness, contour length, intra-nucleus texture data (GLCM is one of the
      methods). In GLCM each nucleus in the tissue image corresponds to one pixel. In
      this approach the most important point is how to define the neighborhood of each
      nucleus. We define three types of neighborhoods of a nucleus, then create the co
      occurrence matrix and apply Haralick feature functions. In each image
      pleomorphism and heterogeneity are then determined quantitatively. For our
      method, one pixel corresponds to one nucleus feature, and we therefore named our
      method Cell Feature Level Co-occurrence Matrix (CFLCM). We tested this method for
      several nucleus features. CONCLUSION: CFLCM is showed as a useful quantitative
      method for pleomorphism and heterogeneity on histopathological image analysis.

PMID- 27688928
TI  - Experience of maintaining laboratory educational website's sustainability.
AB  - Laboratory methodology websites are specialized niche websites. The visibility of
      a niche website transforms it into an authority site on a particular "niche of
      knowledge." This article presents some ways in which a laboratory methodology
      website can maintain its sustainability. The optimal composition of the website
      includes a basic content, a blog, and an ancillary part. This article discusses
      experimenting with the search engine optimization query results page. Strategic
      placement of keywords and even phrases, as well as fragmentation of the post's
      material, can improve the website's visibility to search engines. Hyperlinks open
      a chain reaction of additional links and draw attention to the previous posts.
      Publications in printed periodicals are a substantial part of a niche website
      presence on the Internet. Although this article explores a laboratory website on
      the basis of our hands-on expertise maintaining "Grossing Technology in Surgical
      Pathology" (www.grossing-technology.com) website with a high volume of traffic
      for more than a decade, the recommendations presented here for developing an
      authority website can be applied to other professional specialized websites. The
      authority websites visibility and sustainability are preconditions for
      aggregating them in a specialized educational laboratory portal. 

PMID- 27688929
TI  - Antibody-supervised deep learning for quantification of tumor-infiltrating immune
      cells in hematoxylin and eosin stained breast cancer samples.
AB  - BACKGROUND: Immune cell infiltration in tumor is an emerging prognostic biomarker
      in breast cancer. The gold standard for quantification of immune cells in tissue
      sections is visual assessment through a microscope, which is subjective and semi
      quantitative. In this study, we propose and evaluate an approach based on
      antibody-guided annotation and deep learning to quantify immune cell-rich areas
      in hematoxylin and eosin (H&E) stained samples. METHODS: Consecutive sections of
      formalin-fixed parafin-embedded samples obtained from the primary tumor of twenty
      breast cancer patients were cut and stained with H&E and the pan-leukocyte CD45
      antibody. The stained slides were digitally scanned, and a training set of immune
      cell-rich and cell-poor tissue regions was annotated in H&E whole-slide images
      using the CD45-expression as a guide. In analysis, the images were divided into
      small homogenous regions, superpixels, from which features were extracted using a
      pretrained convolutional neural network (CNN) and classified with a support of
      vector machine. The CNN approach was compared to texture-based classification and
      to visual assessments performed by two pathologists. RESULTS: In a set of 123,442
      labeled superpixels, the CNN approach achieved an F-score of 0.94 (range: 0.92
      0.94) in discrimination of immune cell-rich and cell-poor regions, as compared to
      an F-score of 0.88 (range: 0.87-0.89) obtained with the texture-based
      classification. When compared to visual assessment of 200 images, an agreement of
      90% (kappa = 0.79) to quantify immune infiltration with the CNN approach was
      achieved while the inter-observer agreement between pathologists was 90% (kappa =
      0.78). CONCLUSIONS: Our findings indicate that deep learning can be applied to
      quantify immune cell infiltration in breast cancer samples using a basic
      morphology staining only. A good discrimination of immune cell-rich areas was
      achieved, well in concordance with both leukocyte antigen expression and
      pathologists' visual assessment.

PMID- 27688930
TI  - A novel leadership fellowship in digital pathology.

PMID- 27688931
TI  - Rates of provision of clinical information in the skin biopsy requisition form
      and corresponding encounter visit note.
AB  - BACKGROUND: The skin biopsy requisition form (RF) serves as a key communication
      tool for transfer of relevant information related to skin biopsy between
      clinicians and pathologists. Clinical information in the skin biopsy RF is
      frequently missing or incomplete. OBJECTIVE: To determine the rates of provision
      of critical clinical information necessary for histopathologic interpretation in
      the skin biopsy RF and encounter visit note (EVN). METHODS: A retrospective
      review of 300 RFs and corresponding EVNs from May 1 to 7, 2012, in a tertiary
      care dermatology practice. RESULTS: Age (100%), lesion location (100%), and
      clinical impression (93%) were the most commonly supplied elements in the RF and
      EVN. Clinical elements that were commonly not provided in the RF but present in
      the EVN included sampling method - partial versus complete (46%), duration of
      lesion (54%), morphology of lesion (97%), clinical symptoms (63%), clinical
      photos (63%), previous clinical (97%), and dermatopathologic diagnoses (82%).
      LIMITATIONS: Retrospective study design. CONCLUSIONS: These data suggest that
      while missing critical clinical information in the RF is often present in the
      EVN, some information is still not present in either source.

PMID- 27688932
TI  - Unexpected Angiography Findings and Effects on Management.
AB  - Despite progress in noninvasive imaging with computed tomography and magnetic
      resonance imaging, conventional angiography still contributes to the diagnostic
      workup of oncologic and other diseases. Arteriography can reveal tumors not
      evident on cross-sectional imaging, in addition to defining aberrant or
      unexpected arterial supply to targeted lesions. This additional and potentially
      unanticipated information can alter management decisions during interventional
      procedures. 

PMID- 27688933
TI  - Physical comorbidities increase the risk of psychiatric comorbidity in multiple
      sclerosis.
AB  - BACKGROUND: Risk factors for psychiatric comorbidity in multiple sclerosis (MS)
      are poorly understood. OBJECTIVE: We evaluated the association between physical
      comorbidity and incident depression, anxiety disorder, and bipolar disorder in a
      MS population relative to a matched general population cohort. METHODS: Using
      population-based administrative data from Alberta, Canada we identified 9624
      persons with MS, and 41,194 matches. Using validated case definitions, we
      estimated the incidence of depression, anxiety disorder, and bipolar disorder,
      and their association with physical comorbidities using Cox regression, adjusting
      for age, sex, socioeconomic status, and index year. RESULTS: In both populations,
      men had a lower risk of depression and anxiety disorders than women, as did
      individuals who were >=45 years versus <45 years at the index date. The risk of
      bipolar disorder declined with increasing age. The risks of incident depression
      (HR 1.92; 1.82-2.04), anxiety disorders (HR 1.52; 1.42-1.63), and bipolar
      disorder (HR 2.67; 2.29-3.11) were higher in the MS population than the matched
      population. These associations persisted essentially unchanged after adjustment
      for covariates including physical comorbidities. Multiple physical comorbidities
      were associated with psychiatric disorders in both populations. CONCLUSION:
      Persons with MS are at increased risk of psychiatric comorbidity generally, and
      some physical comorbidities are associated with additional risk.

PMID- 27688935
TI  - A review of novel analytical diagnostics for liquid biopsies: spectroscopic and
      spectrometric serum profiling of primary and secondary brain tumors.
AB  - INTRODUCTION: Spectroscopic and spectrometric analysis of biological samples is
      regarded as quick, cost effective, easy to operate, and spectroscopic sample
      preparation involves minimal sample preparation. RESULTS: Techniques like
      infrared (IR) spectroscopy, surface-enhanced laser desorption/ionization (SELDI)
      mass spectroscopy (MS), and matrix-assisted laser desorption/ionization (MALDI) 
      MS could enable early diagnosis of cancer, disease monitoring, and assessment of
      treatment responses allowing refinement, if required. DISCUSSION: Carrying out
      analytical testing within outpatient clinics would dramatically cut the time
      spent by patients attending different appointments, at different locations, save
      hospital time and resources but importantly would theoretically enable a
      reduction in mortality and morbidity. While the advantages of such a prospect
      seem obvious, this review aims to evaluate the use of human serum spectroscopic
      and spectrometric analysis as a diagnostic tool for brain cancers, creating a
      platform for the future of cancer diagnostics.

PMID- 27688936
TI  - Review of clinical studies of perampanel in adolescent patients.
AB  - AIM: To assess the clinical trial and real-world data for adjunctive perampanel
      in adolescents and develop consensus recommendations to guide the use of
      perampanel in this population in clinical practice. METHODS: In May 2015, 15
      epilepsy experts attended a Consensus Development Meeting to assess the clinical
      trial data for perampanel, specific to the adolescent age group (12-17 years) and
      develop consensus treatment recommendations. RESULTS AND DISCUSSION: Analysis of
      the adolescent subgroup data of three pivotal placebo-controlled, double-blind,
      phase 3 trials investigating perampanel in patients with ongoing focal epileptic
      seizures despite receiving one to three antiepileptic drugs found that perampanel
      4-12 mg was superior to placebo. The tolerability profile of perampanel was
      generally acceptable. Adolescent patients receiving long-term treatment with
      perampanel in an open-label extension study maintained improvements in seizure
      control compared with baseline, with a favorable risk-benefit profile. A phase 2
      study showed that perampanel had no clinically important effects on cognitive
      function, growth, and development. CONCLUSION: Perampanel is a welcome addition
      to the armamentarium of existing antiepileptic drugs as it represents a new
      approach in the management of epilepsy, with a novel mechanism of action, and the
      potential to have a considerable impact on the treatment of adolescents with
      epilepsy.

PMID- 27688934
TI  - Dominant hemisphere functional networks compensate for structural connectivity
      loss to preserve phonological retrieval with aging.
AB  - INTRODUCTION: Loss of hemispheric asymmetry during cognitive tasks has been
      previously demonstrated in the literature. In the context of language, increased
      right hemisphere activation is observed with aging. Whether this relates to
      compensation to preserve cognitive function or dedifferentiation implying loss of
      hemispheric specificity without functional consequence, remains unclear. METHODS:
      With a multifaceted approach, integrating structural and functional imaging data
      during a word retrieval task, in a group of younger and older adults with
      equivalent cognitive performance, we aimed to establish whether interactions
      between hemispheres or reorganization of dominant hemisphere networks preserve
      function. We examined functional and structural connectivity on data from our
      previously published functional activation study. Functional connectivity was
      measured using psychophysiological interactions analysis from the left inferior
      frontal gyrus (LIFG) and the left insula (LINS), based on published literature,
      and the right inferior frontal gyrus (RIFG) based on our previous study. RESULTS:
      Although RIFG showed increased activation, its connectivity decreased with age.
      Meanwhile, LIFG and LINS connected more bilaterally in the older adults. White
      matter integrity, measured by fractional anisotropy (FA) from diffusion tensor
      imaging, decreased significantly in the older group. Importantly, LINS functional
      connectivity to LIFG correlated inversely with FA. CONCLUSIONS: We demonstrate
      that left hemispheric language areas show higher functional connectivity in older
      adults with intact behavioral performance, and thus, may have a role in
      preserving function. The inverse correlation of functional and structural
      connectivity with age is in keeping with emerging literature and merits further
      investigation with tractography studies and in other cognitive domains.

PMID- 27688937
TI  - The anterior versus posterior hippocampal oscillations debate in human spatial
      navigation: evidence from an electrocorticographic case study.
AB  - INTRODUCTION: Hippocampal oscillations have been regularly described as playing a
      dominant role in spatial memory and navigation in rodents. In humans, the
      relative role of anterior versus posterior rhythms during navigational memory is
      not established. METHODS: Here, we tested this hypothesis using direct brain ECoG
      recordings in the anterior and posterior hippocampus of a patient, in a
      navigational task requiring spatial memory. We assessed multiple oscillatory
      bands during encoding and retrieval phases. RESULTS: We found navigation related
      1-3.5 Hz activity during retrieval, both in the anterior and posterior
      hippocampus. Activity between 4 and 8 Hz was identified during both encoding and
      retrieval, only in the anterior hippocampus. CONCLUSIONS: Our findings are
      consistent with the view that an anterior/posterior functional gradient is
      present in the hippocampus, and involves two distinct neuronal networks,
      supporting either encoding or retrieval processes. Although this is a single case
      scenario, these findings suggest that neural oscillations during spatial
      navigation do vary across hippocampal subregions, as a function of encoding
      versus retrieval processes during the mnemonic process. In this single case
      study, the results point to the presence of a dual involvement of multiple
      frequency bands across hippocampal subregions during encoding and retrieval.
      Although these results need generalization, they provide a new perspective on
      distinct physiological properties of the anterior and posterior hippocampus in
      human spatial navigation during encoding and retrieval.

PMID- 27688938
TI  - Reduced specialized processing in psychotic disorder: a graph theoretical
      analysis of cerebral functional connectivity.
AB  - BACKGROUND: Previous research has shown that the human brain can be represented
      as a complex functional network that is characterized by specific topological
      properties, such as clustering coefficient, characteristic path length, and
      global/local efficiency. Patients with psychotic disorder may have alterations in
      these properties with respect to controls, indicating altered efficiency of
      network organization. This study examined graph theoretical changes in relation
      to differential genetic risk for the disorder and aimed to identify clinical
      correlates. METHODS: Anatomical and resting-state MRI brain scans were obtained
      from 73 patients with psychotic disorder, 83 unaffected siblings, and 72
      controls. Topological measures (i.e., clustering coefficient, characteristic path
      length, and small-worldness) were used as dependent variables in a multilevel
      random regression analysis to investigate group differences. In addition,
      associations with (subclinical) psychotic/cognitive symptoms were examined.
      RESULTS: Patients had a significantly lower clustering coefficient compared to
      siblings and controls, with no difference between the latter groups. No group
      differences were observed for characteristic path length and small-worldness.
      None of the topological properties were associated with (sub)clinical psychotic
      and cognitive symptoms. CONCLUSIONS: The reduced ability for specialized
      processing (reflected by a lower clustering coefficient) within highly
      interconnected brain regions observed in the patient group may indicate state
      related network alterations. There was no evidence for an intermediate phenotype
      and no evidence for psychopathology-related alterations.

PMID- 27688939
TI  - A multi-biomarker follow-up study of patients with multiple sclerosis.
AB  - OBJECTIVES: This study aimed to examine the levels of the macrophage marker
      sCD163 and other biomarkers at the time of diagnosis of patients with either
      clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis
      (RRMS), and assess relation to clinical indicators of prognosis, disease activity
      (DA), and changes in the levels of these biomarkers at follow-up. MATERIALS AND
      METHODS: The clinical status and MRI were reevaluated in 56 patients more than 1
      year after diagnosis with a median follow-up time of 2 years. Levels of
      biomarkers in serum and cerebrospinal fluid (CSF) samples were evaluated by
      enzyme-linked immunosorbent assays. RESULTS: There was no significant difference
      in time to DA between patients with CIS and RRMS. A high sCD163 ratio (>0.07) was
      significantly (P = 0.04) associated with time to DA in the untreated patient
      group. In 21 patients reevaluated with serum and CSF samples, the sCD163 ratio
      levels decreased from 0.068 to 0.054 (P = 0.026) in the CIS/RRMS-treated group.
      The CSF CXCL13, CXCL13 ratio, CSF neurofilament light polypeptide and osteopontin
      levels also decreased significantly in the CIS/RRMS-treated group. CONCLUSIONS:
      The levels of all biomarkers changed concurrently with MS treatment. The sCD163
      ratio was identified as a potential novel marker for time to DA.

PMID- 27688940
TI  - CBT reduces CBF: cognitive-behavioral therapy reduces cerebral blood flow in fear
      relevant brain regions in spider phobia.
AB  - BACKGROUND: Imaging studies have provided evidence that cognitive-behavioral
      therapy (CBT) is able to change brain activation in phobic patients in response
      to threatening stimuli. The changes occurred in both emotion-generating and
      modulatory regions. In this study, we use a data-driven approach to explore
      resting state cerebral blood flow (CBF) measured by arterial spin labeling (ASL),
      before and after CBT. METHODS: Eight female patients with spider phobia were
      scanned before and 1 month after an exposure-based group therapy for spider
      phobia. Each MRI session consisted of an ASL resting state measurement acquired
      before and after a symptom provocation task involving the showing of spider
      pictures in the scanner. The first ASL acquisition measured anticipatory anxiety
      and the second measured postprocessing of phobia-relevant stimuli. RESULTS:
      Cognitive-behavioral therapy significantly reduced spider phobic symptoms in all
      patients. Symptom reduction during anticipatory anxiety was accompanied by
      reduced bilateral CBF in the parahippocampal gyrus, ventral anterior thalamus,
      Brodmann area 8, and the anterior cingulate cortex. During postprocessing of
      phobia-relevant stimuli, patients showed reduced CBF in the bilateral insula,
      components of the motor cortex, and areas associated with language functions.
      CONCLUSIONS: Longitudinal CBF dynamics following CBT were in concordance with
      results from several studies using BOLD fMRI to investigate the effects of
      psychotherapy on brain activity. CBF can be quantified by ASL, with the principal
      advantage of sensitivity to slow variations in neural activity and task
      independence. Therefore, ASL may be a suitable method for monitoring and
      evaluating the efficacy of psychotherapy or pharmacotherapy approaches.

PMID- 27688941
TI  - Long-term acclimatization to high-altitude hypoxia modifies interhemispheric
      functional and structural connectivity in the adult brain.
AB  - BACKGROUND: Structural and functional networks can be reorganized to adjust to
      environmental pressures and physiologic changes in the adult brain, but such
      processes remain unclear in prolonged adaptation to high-altitude (HA) hypoxia.
      This study aimed to characterize the interhemispheric functionally and
      structurally coupled modifications in the brains of adult HA immigrants. METHODS:
      We performed resting-state functional magnetic resonance imaging (fMRI) and
      diffusion tensor imaging (DTI) in 16 adults who had immigrated to the Qinghai
      Tibet Plateau (2300-4400 m) for 2 years and in 16 age-matched sea-level (SL)
      controls. A recently validated approach of voxel-mirrored homotopic connectivity
      (VMHC) was employed to examine the interhemispheric resting-state functional
      connectivity. Areas showing changed VMHC in HA immigrants were selected as
      regions of interest for follow-up DTI tractography analysis. The fiber parameters
      of fractional anisotropy and fiber length were obtained. Cognitive and
      physiological assessments were made and correlated with the resulting image
      metrics. RESULTS: Compared with SL controls, VMHC in the bilateral visual cortex
      was significantly increased in HA immigrants. The mean VMHC value extracted
      within the visual cortex was positively correlated with hemoglobin concentration.
      Moreover, the path length of the commissural fibers connecting homotopic visual
      areas was increased in HA immigrants, covarying positively with VMHC.
      CONCLUSIONS: These observations are the first to demonstrate interhemispheric
      functional and structural connectivity resilience in the adult brain after
      prolonged HA acclimatization independent of inherited and developmental effects,
      and the coupled modifications in the bilateral visual cortex indicate important
      neural compensatory mechanisms underlying visual dysfunction in physiologically
      well-acclimatized HA immigrants. The study of human central adaptation to extreme
      environments promotes the understanding of our brain's capacity for survival.

PMID- 27688942
TI  - Collateral state and the effect of endovascular reperfusion therapy on clinical
      outcome in ischemic stroke patients.
AB  - PURPOSE: Clinically successful endovascular therapy (EVT) in ischemic stroke
      requires reliable noninvasive pretherapeutic selection criteria. We investigated
      the association of imaging parameters including CT angiographic collaterals and
      degree of reperfusion with clinical outcome after EVT. METHODS: In our database,
      we identified 93 patients with large vessel occlusion in the anterior circulation
      treated with EVT. Besides clinical data, we assessed the baseline Alberta Stroke
      Program Early CT score (ASPECTS) on noncontrast CT (NCCT) and CT angiography
      (CTA) source images, collaterals (CT-CS) and clot burden score (CBS) on CTA and
      the degree of reperfusion after EVT on angiography. Three readers, blinded to
      clinical information, evaluated the images in consensus. Data-driven
      multivariable ordinal regression analysis identified predictors of good outcome
      after 90 days as measured with the modified Rankin Scale. RESULTS: Successful
      angiographic reperfusion (OR 26.50; 95%-CI 9.33-83.61) and good collaterals (OR
      9.69; 95%-CI 2.28-59.27) were independent predictors of favorable outcome along
      with female sex (OR 0.35; 95%-CI 0.14-0.85), younger age (OR 0.88; 95%-CI 0.83
      0.92) and higher NCCT ASPECTS (OR 2.54; 95%-CI 1.01-6.63). Outcome was best in
      patients with good collaterals and successful reperfusion, but there was no
      statistical interaction between collaterals and reperfusion. CONCLUSIONS: CTA
      collateral status was the strongest pretherapeutic predictor of favorable outcome
      in ischemic stroke patients treated with EVT. CTA-collaterals are thus well
      suited for patient selection in EVT. However, the independent effect of
      reperfusion on outcome tended to be stronger than that of CTA-collaterals.

PMID- 27688943
TI  - Early-life single-episode sevoflurane exposure impairs social behavior and
      cognition later in life.
AB  - BACKGROUND: Single-episode anesthetic exposure is the most prevalent surgery
      related incidence among young children in the United States. Although numerous
      studies have used animals to model the effects of neonatal anesthetics on
      behavioral changes later on in life, our understanding of the functional
      consequences to the developing brain in a comprehensive and clinically relevant
      manner is unclear. METHODS: The volatile anesthetic, sevoflurane (sevo) was
      administered to C57BL6 postnatal day 7 (P7) mice in a 40% oxygen and 60% nitrogen
      gas mixture. In order to examine the effects of sevo alone on the developing
      brain in a clinically relevant manner, mice were exposed to an average of 2.38 +/
      0.11% sevo for 2 h. No sevo (control) mice were treated in an identical manner
      without sevo exposure. Mice were examined for cognition and neuropsychiatric-like
      behavioral changes at 1-5 months of age. RESULTS: Using the active place
      avoidance (APA) test and the novel object recognition (NOR) test, we demonstrated
      that P7 sevo-treated mice showed a deficit in learning and memory both during
      periadolescence and adulthood. We then employed a battery of neuropsychiatric
      like behavioral tests to examine social interaction, communication, and
      repetitive behavior. Interestingly, compared to the no-sevo-treated group, sevo
      treated mice showed significant reductions in the time interacting with a novel
      mouse (push-crawl and following), time and interaction in a chamber with a novel
      mouse, and time sniffing a novel social odor. CONCLUSIONS: Our study established
      that single-episode, 2-h sevo treatment during early life impairs cognition later
      on in life. With this approach, we also observed neuropsychiatric-like behavior
      changes such as social interaction deficits in the sevo-treated mice. This study
      elucidated the effects of a clinically relevant single-episode sevo application,
      given during the neonatal period, on neurodevelopmental behavioral changes later
      on in life.

PMID- 27688944
TI  - Reliable measurements of brain atrophy in individual patients with multiple
      sclerosis.
AB  - INTRODUCTION: As neurodegeneration is recognized as a major contributor to
      disability in multiple sclerosis (MS), brain atrophy quantification could have a
      high added value in clinical practice to assess treatment efficacy and disease
      progression, provided that it has a sufficiently low measurement error to draw
      meaningful conclusions for an individual patient. METHOD: In this paper, we
      present an automated longitudinal method based on Jacobian integration for
      measuring whole-brain and gray matter atrophy based on anatomical magnetic
      resonance images (MRI), named MSmetrix. MSmetrix is specifically designed to
      measure atrophy in patients with MS, by including iterative lesion segmentation
      and lesion filling based on FLAIR and T1-weighted MRI scans. RESULTS: MS metrix
      is compared with SIENA with respect to test-retest error and consistency,
      resulting in an average test-retest error on an MS data set of 0.13% (MS metrix)
      and 0.17% (SIENA) and a consistency error of 0.07% (MS metrix) and 0.05% (SIENA).
      On a healthy subject data set including physiological variability the test-retest
      is 0.19% (MS metrix) and 0.31% (SIENA). CONCLUSION: Therefore, we can conclude
      that MSmetrix could be of added value in clinical practice for the follow-up of
      treatment and disease progression in MS patients.

PMID- 27688947
TI  - Erratum: Cortical folding of the preterm brain: a longitudinal analysis of
      extremely preterm born neonates using spectral matching.
AB  - [This corrects the article DOI: 10.1002/brb3.488.].

PMID- 27688948
TI  - Point - Counterpoint.

PMID- 27688946
TI  - Concept of an upright wearable positron emission tomography imager in humans.
AB  - BACKGROUND: Positron Emission Tomography (PET) is traditionally used to image
      patients in restrictive positions, with few devices allowing for upright, brain
      dedicated imaging. Our team has explored the concept of wearable PET imagers
      which could provide functional brain imaging of freely moving subjects. To test
      feasibility and determine future considerations for development, we built a
      rudimentary proof-of-concept prototype (Helmet_PET) and conducted tests in
      phantoms and four human volunteers. METHODS: Twelve Silicon Photomultiplier-based
      detectors were assembled in a ring with exterior weight support and an interior
      mechanism that could be adjustably fitted to the head. We conducted brain phantom
      tests as well as scanned four patients scheduled for diagnostic F(18-) FDG PET/CT
      imaging. For human subjects the imager was angled such that field of view
      included basal ganglia and visual cortex to test for typical resting-state
      pattern. Imaging in two subjects was performed ~4 hr after PET/CT imaging to
      simulate lower injected F(18-) FDG dose by taking advantage of the natural
      radioactive decay of the tracer (F(18) half-life of 110 min), with an estimated
      imaging dosage of 25% of the standard. RESULTS: We found that imaging with a
      simple lightweight ring of detectors was feasible using a fraction of the
      standard radioligand dose. Activity levels in the human participants were
      quantitatively similar to standard PET in a set of anatomical ROIs. Typical
      resting-state brain pattern activation was demonstrated even in a 1 min scan of
      active head rotation. CONCLUSION: To our knowledge, this is the first
      demonstration of imaging a human subject with a novel wearable PET imager that
      moves with robust head movements. We discuss potential research and clinical
      applications that will drive the design of a fully functional device. Designs
      will need to consider trade-offs between a low weight device with high mobility
      and a heavier device with greater sensitivity and larger field of view.

PMID- 27688945
TI  - Kappa-opioid receptors differentially regulate low and high levels of ethanol
      intake in female mice.
AB  - INTRODUCTION: Studies in laboratory animals and humans indicate that endogenous
      opioids play an important role in regulating the rewarding value of various
      drugs, including ethanol (EtOH). Indeed, opioid antagonists are currently a front
      line treatment for alcoholism in humans. Although roles for mu- and delta-opioid
      receptors have been characterized, the contribution of kappa-opioid receptors
      (KORs) is less clear. There is evidence that changes in KOR system function can
      decrease or increase EtOH drinking, depending on test conditions. For example,
      female mice lacking preprodynorphin - the precursor to the endogenous KOR ligand
      dynorphin - have reduced EtOH intake. Considering that KORs can regulate dopamine
      (DA) transmission, we hypothesized that KORs expressed on DA neurons would play a
      prominent role in EtOH intake in females. METHODS: We used a Cre/loxP
      recombination strategy to ablate KORs throughout the body or specifically on
      dopamine uptake transporter (DAT)-expressing neurons to investigate the role of
      KORs on preference for and intake of EtOH (2-bottle choice), the transition from
      moderate to excessive EtOH drinking (intermittent EtOH access), and binge EtOH
      drinking (drinking in the dark [DID]). RESULTS: KOR deletion decreased preference
      for EtOH, although this effect was less pronounced when EtOH intake increased
      beyond relatively low levels. DISCUSSION: Our findings indicate that KOR
      activation increases EtOH drinking via effects mediated, at least in part, by
      KORs on DA neurons. While the mechanisms of this regulation remain unknown,
      previous work suggests that alterations in negative reinforcement processes or
      sensitivity to the sensory properties of EtOH can affect preference and intake.

PMID- 27688949
TI  - Commentary on Disparities in Infant Mortality Due to Congenital Anomalies on
      Guam.

PMID- 27688950
TI  - Response to Commentary on Disparities in Infant Mortality Due to Congenital
      Anomalies on Guam.

PMID- 27688951
TI  - Significance of Concussions in Hawai'i: From Land to Sea.
AB  - Head injuries are a particular concern in Hawai'i given the large military
      population, the presence of many land and water sports such as football and
      surfing, and the lenient helmet laws for motorcycle and bicycle riders. Physical,
      psychological, and cognitive symptoms from single or repeated concussions can
      affect an individual's reentry to society and activity. Current literature
      indicates that repeated head injuries are associated with chronic traumatic
      encephalopathy (CTE) which is thought to lead to dementia. This paper reviews
      literature discussing causes of concussion including its incidence and prevalence
      in Hawai'i. Furthermore, the neurophysiological and neurobiological etiologies
      are discussed followed by an overview of methods for identification and
      management of concussion. The paper serves as information for professionals in
      the community such as educators, military personnel, and healthcare workers to
      identify risks of concussion, management of symptoms, and to connect with
      resources and programs available in Hawai'i.

PMID- 27688952
TI  - Self-Reported Experiences of Discrimination and Depression in Native Hawaiians.
AB  - Discrimination is an acute and chronic stressor that negatively impacts the
      health of many ethnic groups in the United States. Individuals who perceive
      increased levels of discrimination are at risk of experiencing psychological
      distress and symptoms of depression. No study to date has examined the
      relationship between perceived discrimination and mental health in Native
      Hawaiians. The purpose of this study is to explore the relationship between
      perceived discrimination and depression based on the Homestead Health Survey
      mailed to Native Hawaiian residents of Hawaiian Home Lands. This study also
      explores the role of cultural identity and how it may impact experiences of
      discrimination and symptoms of depression. Based on cross-sectional data obtained
      from 104 Native Hawaiian residents, a significant positive correlation was found
      between perceived discrimination and symptoms of depression (r= 0.32, P<.001).
      Cultural identity did not significantly correlate with discrimination or
      depression. Multiple linear regression analyses indicate that the relationship
      between depression and discrimination remained statistically significant
      (coefficient estimate of 0.18; P<.01), after accounting for differences in socio
      demographics and degree of identification with the Native Hawaiian and American
      cultures. These findings are consistent with other studies that have focused on
      the effects of discrimination on psychological wellbeing for other ethnic
      minority populations.

PMID- 27688954
TI  - Medical School Hotline: Liaison Committee on Medical Education Accreditation,
      Part VIII: Faculty Development.

PMID- 27688953
TI  - Recovery of Left Ventricular Function After Percutaneous Coronary Intervention
      Compared to Coronary Artery Bypass Grafting in Patients with Multi-Vessel
      Coronary Disease and Left Ventricular Dysfunction.
AB  - Recovery of left ventricular (LV) function after revascularization has been
      described for coronary artery bypass grafting (CABG); however, LV recovery after
      percutaneous coronary intervention (PCI), and how it compares to CABG has not
      been well described in the literature. The aim of this single center
      retrospective study was to evaluate LV recovery in patients with severely reduced
      LV function undergoing PCI compared to those undergoing CABG. Patients with LV
      ejection fraction (LVEF) < 40% and multivessel coronary artery disease (CAD)
      undergoing revascularization with either CABG (n=16) or PCI (n=176), and with 12
      months of follow up data were included in the study. LVEF at baseline exhibited
      significant differences between PCI (28.5 +/- 8.0) and CABG (24.2 +/- 6.8) groups
      (P=.05). LVEF recovery at 6-month follow up showed no difference between PCI and
      CABG groups. LVEF recovery differences at one-year follow-up was significantly
      different between PCI (4.82) and CABG (15.25) groups (P=.005). Patients with
      severely reduced LV function undergoing multivessel PCI had a statistically
      significant increase in LVEF over time; however patients undergoing CABG
      demonstrated greater gains in LVEF over the same time period. Surgical
      revascularization with CABG may be a procedure of choice in patients with
      depressed LV function and multivessel CAD.

PMID- 27688955
TI  - Insights in Public Health: All About the Insurance: The US health-Care System
      Through a Foreigner's Eyes.
AB  - Hawai'i had high insurance coverage rates even before the Affordable Health Care
      Act and continues to have a high percentage of the population with health
      insurance today. However, high insurance rates can disguise wide variation in
      what is covered and what it costs. In this essay, an Australian Masters in Public
      Health student from the University of Hawai'i considers the strengths and
      weaknesses of insurance coverage in the US health-care system when her friend
      "Peter" becomes seriously ill.

PMID- 27688957
TI  - Are sites with multiple single nucleotide variants in cancer genomes a
      consequence of drivers, hypermutable sites or sequencing errors?
AB  - Across independent cancer genomes it has been observed that some sites have been
      recurrently hit by single nucleotide variants (SNVs). Such recurrently hit sites
      might be either (i) drivers of cancer that are postively selected during
      oncogenesis, (ii) due to mutation rate variation, or (iii) due to sequencing and
      assembly errors. We have investigated the cause of recurrently hit sites in a
      dataset of >3 million SNVs from 507 complete cancer genome sequences. We find
      evidence that many sites have been hit significantly more often than one would
      expect by chance, even taking into account the effect of the adjacent nucleotides
      on the rate of mutation. We find that the density of these recurrently hit sites
      is higher in non-coding than coding DNA and hence conclude that most of them are
      unlikely to be drivers. We also find that most of them are found in parts of the
      genome that are not uniquely mappable and hence are likely to be due to mapping
      errors. In support of the error hypothesis, we find that recurently hit sites are
      not randomly distributed across sequences from different laboratories. We fit a
      model to the data in which the rate of mutation is constant across sites but the
      rate of error varies. This model suggests that ~4% of all SNVs are errors in this
      dataset, but that the rate of error varies by thousands-of-fold between sites. 

PMID- 27688959
TI  - Polymorphic DNA microsatellite markers for forensic individual identification and
      parentage analyses of seven threatened species of parrots (family Psittacidae).
AB  - The parrot family represents one of the bird group with the largest number of
      endangered species, as a result of habitat destruction and illegal trade. This
      illicit traffic involves the smuggling of eggs and animals, and the laundering
      through captive breeding facilities of wild-caught animals. Despite the huge
      potential of wildlife DNA forensics to determine with conclusive evidence illegal
      trade, current usage of DNA profiling approaches in parrots has been limited by
      the lack of suitable molecular markers specifically developed for the focal
      species and by low cross-species polymorphism. In this study, we isolated DNA
      microsatellite markers in seven parrot species threatened with extinction
      (Amazona brasiliensis, A. oratrix, A. pretrei, A. rhodocorytha, Anodorhynchus
      leari, Ara rubrogenys and Primolius couloni). From an enriched genomic library
      followed by 454 pyrosequencing, we characterized a total of 106 polymorphic
      microsatellite markers (mostly tetranucleotides) in the seven species and tested
      them across an average number of 19 individuals per species. The mean number of
      alleles per species and across loci varied from 6.4 to 8.3, with the mean
      observed heterozygosities ranging from 0.65 to 0.84. Identity and parentage
      exclusion probabilities were highly discriminatory. The high variability
      displayed by these microsatellite loci demonstrates their potential utility to
      perform individual genotyping and parentage analyses, in order to develop a DNA
      testing framework to determine illegal traffic in these threatened species. 

PMID- 27688958
TI  - Contributions to the functional morphology of caudate skulls: kinetic and
      akinetic forms.
AB  - A strongly ossified and rigid skull roof, which prevents parietal kinesis, has
      been reported for the adults of all amphibian clades. Our MU-CT investigations
      revealed that the Buresch's newt (Triturus ivanbureschi) possess a peculiar
      cranial construction. In addition to the typical amphibian pleurokinetic
      articulation between skull roof and palatoquadrate associated structures, we
      found flexible connections between nasals and frontals (prokinesis), vomer and
      parasphenoid (palatokinesis), and between frontals and parietals (mesokinesis).
      This is the first description of mesokinesis in urodelans. The construction of
      the skull in the Buresch's newts also indicates the presence of an articulation
      between parietals and the exocipitals, discussed as a possible kind of
      metakinesis. The specific combination of pleuro-, pro-, meso-, palato-, and
      metakinetic skull articulations indicate to a new kind of kinetic systems unknown
      for urodelans to this date. We discuss the possible neotenic origin of the skull
      kinesis and pose the hypothesis that the kinesis in T. ivanbureschi increases the
      efficiency of fast jaw closure. For that, we compared the construction of the
      skull in T. ivanbureschi to the akinetic skull of the Common fire salamander
      Salamandra salamandra. We hypothesize that the design of the skull in the purely
      terrestrial living salamander shows a similar degree of intracranial mobility.
      However, this mobility is permitted by elasticity of some bones and not by true
      articulation between them. We comment on the possible relation between the skull
      construction and the form of prey shaking mechanism that the species apply to
      immobilize their victims. 

PMID- 27688960
TI  - Parameter estimation in tree graph metabolic networks.
AB  - We study the glycosylation processes that convert initially toxic substrates to
      nutritionally valuable metabolites in the flavonoid biosynthesis pathway of
      tomato (Solanum lycopersicum) seedlings. To estimate the reaction rates we use
      ordinary differential equations (ODEs) to model the enzyme kinetics. A popular
      choice is to use a system of linear ODEs with constant kinetic rates or to use
      Michaelis-Menten kinetics. In reality, the catalytic rates, which are affected
      among other factors by kinetic constants and enzyme concentrations, are changing
      in time and with the approaches just mentioned, this phenomenon cannot be
      described. Another problem is that, in general these kinetic coefficients are not
      always identifiable. A third problem is that, it is not precisely known which
      enzymes are catalyzing the observed glycosylation processes. With several hundred
      potential gene candidates, experimental validation using purified target proteins
      is expensive and time consuming. We aim at reducing this task via mathematical
      modeling to allow for the pre-selection of most potential gene candidates. In
      this article we discuss a fast and relatively simple approach to estimate time
      varying kinetic rates, with three favorable properties: firstly, it allows for
      identifiable estimation of time dependent parameters in networks with a tree-like
      structure. Secondly, it is relatively fast compared to usually applied methods
      that estimate the model derivatives together with the network parameters.
      Thirdly, by combining the metabolite concentration data with a corresponding
      microarray data, it can help in detecting the genes related to the enzymatic
      processes. By comparing the estimated time dynamics of the catalytic rates with
      time series gene expression data we may assess potential candidate genes behind
      enzymatic reactions. As an example, we show how to apply this method to select
      prominent glycosyltransferase genes in tomato seedlings. 

PMID- 27688961
TI  - In situ visualization of bacterial populations in coral tissues: pitfalls and
      solutions.
AB  - In situ visualization of microbial communities within their natural habitats
      provides a powerful approach to explore complex interactions between
      microorganisms and their macroscopic hosts. Specifically, the application of
      fluorescence in situ hybridization (FISH) to simultaneously identify and
      visualize diverse microbial taxa associated with coral hosts, including symbiotic
      algae (Symbiodinium), Bacteria, Archaea, Fungi and protists, could help untangle
      the structure and function of these diverse taxa within the coral holobiont.
      However, the application of FISH approaches to coral samples is constrained by
      non-specific binding of targeted rRNA probes to cellular structures within the
      coral animal tissues (including nematocysts, spirocysts, granular gland cells
      within the gastrodermis and cnidoglandular bands of mesenterial filaments). This
      issue, combined with high auto-fluorescence of both host tissues and
      endosymbiotic dinoflagellates (Symbiodinium), make FISH approaches for analyses
      of coral tissues challenging. Here we outline the major pitfalls associated with
      applying FISH to coral samples and describe approaches to overcome these
      challenges. 

PMID- 27688963
TI  - A comparison between traditional and measurement-error growth models for weakfish
      Cynoscion regalis.
AB  - Inferring growth for aquatic species is dependent upon accurate descriptions of
      age-length relationships, which may be degraded by measurement error in observed
      ages. Ageing error arises from biased and/or imprecise age determinations as a
      consequence of misinterpretation by readers or inability of ageing structures to
      accurately reflect true age. A Bayesian errors-in-variables (EIV) approach (i.e.,
      measurement-error modeling) can account for ageing uncertainty during nonlinear
      growth curve estimation by allowing observed ages to be parametrically modeled as
      random deviates. Information on the latent age composition then comes from the
      specified prior distribution, which represents the true age structure of the
      sampled fish population. In this study, weakfish growth was modeled by means of
      traditional and measurement-error von Bertalanffy growth curves using otolith- or
      scale-estimated ages. Age determinations were assumed to be log-normally
      distributed, thereby incorporating multiplicative error with respect to ageing
      uncertainty. The prior distribution for true age was assumed to be uniformly
      distributed between +/-4 of the observed age (yr) for each individual.
      Measurement-error growth models described weakfish that reached larger sizes but
      at slower rates, with median length-at-age being overestimated by traditional
      growth curves for the observed age range. In addition, measurement-error models
      produced slightly narrower credible intervals for parameters of the von
      Bertalanffy growth function, which may be an artifact of the specified prior
      distributions. Subjectivity is always apparent in the ageing of fishes and it is
      recommended that measurement-error growth models be used in conjunction with
      otolith-estimated ages to accurately capture the age-length relationship that is
      subsequently used in fisheries stock assessment and management. 

PMID- 27688962
TI  - Environment and host species shape the skin microbiome of captive neotropical
      bats.
AB  - BACKGROUND: A wide range of microorganisms inhabit animal skin. This microbial
      community (microbiome) plays an important role in host defense against pathogens
      and disease. Bats (Chiroptera: Mammalia) are an ecologically and evolutionarily
      diversified group with a relatively unexplored skin microbiome. The bat skin
      microbiome could play a role in disease resistance, for example, to white nose
      syndrome (WNS), an infection which has been devastating North American bat
      populations. However, fundamental knowledge of the bat skin microbiome is needed
      before understanding its role in health and disease resistance. Captive
      neotropical frugivorous bats Artibeus jamaicensis and Carollia
      perspicillataprovide a simple controlled system in which to characterize the
      factors shaping the bat microbiome. Here, we aimed to determine the relative
      importance of habitat and host species on the bat skin microbiome. METHODS: We
      performed high-throughput 16S rRNA gene sequencing of the skin microbiome of two
      different bat species living in captivity in two different habitats. In the first
      habitat, A. jamaicensis and C. perspicillata lived together, while the second
      habitat contained only A. jamaicensis. RESULTS: We found that both habitat and
      host species shape the composition and diversity of the skin microbiome, with
      habitat having the strongest influence. Cohabitating A. jamaicensis and C.
      perspicillata shared more similar skin microbiomes than members of the same
      species (A. jamaicensis) across two habitats. DISCUSSION: These results suggest
      that in captivity, the skin microbial community is homogenised by the shared
      environments and individual proximities of bats living together in the same
      habitat, at the expense of the innate host species factors. The predominant
      influence of habitat suggests that environmental microorganisms or pathogens
      might colonize bat skin. We also propose that bat populations could differ in
      pathogen susceptibility depending on their immediate environment and habitat.

PMID- 27688964
TI  - Successful population establishment from small introductions appears to be less
      common than believed.
AB  - Although small populations are at high risk of extinction, there are regular
      reports in the scientific literature of purported small, isolated, persistent
      populations. One source of evidence of the viability of small populations comes
      from the alleged successful introduction of species to areas outside their
      original range from introductions of few individuals. We reviewed the examples
      from introduction compendia on deliberate translocations of birds, and the
      original sources, to identify and evaluate purported examples of successful
      establishments from small introductions. We found 23 purportedly successful
      introductions from few (<30) individuals. After assessing original sources, we
      found that two of the claims were substantiated; the rest were ambiguous or could
      be rejected as examples, primarily due to a lack of evidence in original sources
      of the number of birds released and because of supplemental individuals from
      other releases, releases in nearby regions, and the possibility of natural
      invasion. Our results suggest that reports of successful establishment of birds
      from introductions of few individuals have been overstated. These results
      strengthen the relationship previously reported between propagule pressure and
      likelihood of establishment, and support the lack of viability of small
      populations presumed by population theory. We suggest that analyses of
      introduction failure and success would benefit from excluding studies where
      introduction effort is unknown or unreliably documented. 

PMID- 27688966
TI  - In vitro and in vivo comparison of transport media for detecting nasopharyngeal
      carriage of Streptococcus pneumoniae.
AB  - BACKGROUND: As a standard method for pneumococcal carriage studies, the World
      Health Organization recommends nasopharyngeal swabs be transported and stored at
      cool temperatures in a medium containing skim-milk, tryptone, glucose and
      glycerol (STGG). An enrichment broth used for transport at room temperature in
      three carriage studies performed in Norway may have a higher sensitivity than
      STGG. We therefore compared the media in vitro and in vivo. METHODS: For the in
      vitro component, three strains (serotype 4, 19F and 3) were suspended in STGG and
      enrichment broth. Recovery was compared using latex agglutination, quantification
      of bacterial loads by real-time PCR of the lytA gene, and counting colonies from
      incubated plates. For the in vivo comparison, paired swabs were obtained from 100
      children and transported in STGG at cool temperatures or in enrichment broth at
      room temperature. Carriage was identified by latex agglutination and confirmed by
      Quellung reaction. RESULTS: In vitro, the cycle threshold values obtained by PCR
      did not differ between the two media (p = 0.853) and no clear difference in
      colony counts was apparent after incubation (p = 0.593). In vivo, pneumococci
      were recovered in 46% of swabs transported in STGG and 51% of those transported
      in enrichment broth (Kappa statistic 0.90, p = 0.063). DISCUSSION: Overall, no
      statistical differences in sensitivity were found between STGG and enrichment
      broth. Nevertheless, some serotype differences were observed and STGG appeared
      slightly less sensitive than enrichment broth for detection of nasopharyngeal
      carriage of pneumococci by culturing. We recommend the continued use of STGG for
      transport and storage of nasopharyngeal swabs in pneumococcal carriage studies
      for the benefit of comparability between studies and settings, including more
      resource-limited settings.

PMID- 27688965
TI  - Short-term MRI measurements as predictors of EDSS progression in relapsing
      remitting multiple sclerosis: grey matter atrophy but not lesions are predictive
      in a real-life setting.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is the best biomarker of
      inflammatory disease activity in relapsing remitting Multiple Sclerosis (RRMS) so
      far but the association with disability is weak. Appearance of new MRI-lesions is
      used to evaluate response to immunotherapies in individual patients as well as
      being the most common primary outcome in phase-2 trials. Measurements of brain
      atrophy show promising outcomes in natural cohort studies and some phase-2
      trials. From a theoretical perspective they might represent irreversible
      neurodegeneration and be more closely associated with disability. However, these
      atrophy measurements are not yet established as prognostic factors in real-life
      clinical routine. High field MRI has improved image quality and resolution and
      new methods to measure atrophy dynamics have become available. OBJECTIVE: To
      investigate the predictive value of MRI classification criteria in to high/low
      atrophy and inflammation groups, and to explore predictive capacity of two
      consecutive routine MRI scans for disability progression in RRMS in a real-life
      prospective cohort. METHODS: 82 RRMS-patients (40 untreated, 42 treated with
      immunotherapies, mean age 40 years, median Expanded Disability Status Scale
      (EDSS) of 2, underwent two clinically indicated MRI scans (3 Tesla) within 5-14
      months, and EDSS assessment after a mean of 3.0 (1.5-4.2) years. We investigated
      the predictive value of predefined classifications in low/high inflammatory and
      atrophy groups for EDSS progression (>=1.5 if baseline EDSS = 0, >=1.0 if
      baseline EDSS <5, >=0.5 for other) by chi-square tests and by analysis of
      variance (ANOVA). The classifications were based on current scientific or
      clinical recommendation (e.g., treatment response criteria). Brain atrophy was
      assessed with three different methods (SIENA, SIENAX, and FreeSurfer). Post-hoc
      analyses aimed to explore clinical data and dynamics of MRI outcomes as
      predictors in multivariate linear and logit models. RESULTS: Progression was
      observed in 24% of patients and was independent from treatment status. None of
      the predefined classifications were predictive for progression. Explorative post
      hoc analyses found lower baseline EDSS and higher grey matter atrophy
      (FreeSurfer) as best predictors (R (2) = 0.29) for EDSS progression and the
      accuracy was overall good (Area under the curve = 0.81). CONCLUSION: Beside EDSS
      at baseline, short-term grey matter atrophy is predictive for EDSS progression in
      treated and untreated RRMS. The development of atrophy measurements for
      individual risk counselling and evaluation of treatment response seems possible,
      but needs further validation in larger cohorts. MRI-atrophy estimates from the
      FreeSurfer toolbox seem to be more reliable than older methods.

PMID- 27688967
TI  - Evolutionary morphology of the rabbit skull.
AB  - The skull of leporids (rabbits and hares) is highly transformed, typified by
      pronounced arching of the dorsal skull and ventral flexion of the facial region
      (i.e., facial tilt). Previous studies show that locomotor behavior influences
      aspects of cranial shape in leporids, and here we use an extensive 3D geometric
      morphometrics dataset to further explore what influences leporid cranial
      diversity. Facial tilt angle, a trait that strongly correlates with locomotor
      mode, significantly predicts the cranial shape variation captured by the primary
      axis of cranial shape space, and describes a small proportion (13.2%) of overall
      cranial shape variation in the clade. However, locomotor mode does not correlate
      with overall cranial shape variation in the clade, because there are two district
      morphologies of generalist species, and saltators and cursorial species have
      similar morphologies. Cranial shape changes due to phyletic size change
      (evolutionary allometry) also describes a small proportion (12.5%) of cranial
      shape variation in the clade, but this is largely driven by the smallest living
      leporid, the pygmy rabbit (Brachylagus idahoensis). By integrating phylogenetic
      history with our geometric morphometric data, we show that the leporid cranium
      exhibits weak phylogenetic signal and substantial homoplasy. Though these results
      make it difficult to reconstruct what the 'ancestral' leporid skull looked like,
      the fossil records suggest that dorsal arching and facial tilt could have
      occurred before the origin of the crown group. Lastly, our study highlights the
      diversity of cranial variation in crown leporids, and highlights a need for
      additional phylogenetic work that includes stem (fossil) leporids and includes
      morphological data that captures the transformed morphology of rabbits and hares.

PMID- 27688969
TI  - Development and characterization of fourteen novel microsatellite markers for the
      chestnut short-tailed fruit bat (Carollia castanea), and cross-amplification to
      related species.
AB  - Rapid anthropogenic land use change threatens the primary habitat of the Chestnut
      short-tailed bat (Carollia castanea) throughout much of its range. Information on
      population genetic structure can inform management strategies for this widespread
      frugivorous bat, and effective protection of C. castanea will also benefit the
      more than 20 mutualistic plant species of which this bat is the primary seed
      disperser. To facilitate understanding of population genetic structure in this
      species, fourteen novel microsatellite markers were developed using restriction
      site-associated DNA libraries and Illumina sequencing and tested on 28
      individuals from 13 locations in Costa Rica. These are the first microsatellite
      markers developed for C. castanea. All loci were polymorphic, with number of
      alleles ranging from 2-11 and average observed heterozygosity of 0.631. Markers
      were also cross-amplified in three additional frugivorous bat species threatened
      by habitat loss and fragmentation: Sowell's short-tailed bat (Carollia sowelli),
      Seba's short-tailed bat (Carollia perspicillata), and the Jamaican fruit bat
      (Artibeus jamaicensis), and 10, 11, and 8 were polymorphic, respectively. 

PMID- 27688970
TI  - Blue hypertext is a good design decision: no perceptual disadvantage in reading
      and successful highlighting of relevant information.
AB  - BACKGROUND: Highlighted text in the Internet (i.e., hypertext) is predominantly
      blue and underlined. The perceptibility of these hypertext characteristics was
      heavily questioned by applied research and empirical tests resulted in
      inconclusive results. The ability to recognize blue text in foveal and parafoveal
      vision was identified as potentially constrained by the low number of foveally
      centered blue light sensitive retinal cells. The present study investigates if
      foveal and parafoveal perceptibility of blue hypertext is reduced in comparison
      to normal black text during reading. METHODS: A silent-sentence reading study
      with simultaneous eye movement recordings and the invisible boundary paradigm,
      which allows the investigation of foveal and parafoveal perceptibility,
      separately, was realized (comparing fixation times after degraded vs. un-degraded
      parafoveal previews). Target words in sentences were presented in either black or
      blue and either underlined or normal. RESULTS: No effect of color and
      underlining, but a preview benefit could be detected for first pass reading
      measures. Fixation time measures that included re-reading, e.g., total viewing
      times, showed, in addition to a preview effect, a reduced fixation time for not
      highlighted (black not underlined) in contrast to highlighted target words
      (either blue or underlined or both). DISCUSSION: The present pattern reflects no
      detectable perceptual disadvantage of hyperlink stimuli but increased attraction
      of attention resources, after first pass reading, through highlighting. Blue or
      underlined text allows readers to easily perceive hypertext and at the same time
      readers re-visited highlighted words longer. On the basis of the present
      evidence, blue hypertext can be safely recommended to web designers for future
      use.

PMID- 27688968
TI  - Hyperbrain features of team mental models within a juggling paradigm: a proof of
      concept.
AB  - BACKGROUND: Research on cooperative behavior and the social brain exists, but
      little research has focused on real-time motor cooperative behavior and its
      neural correlates. In this proof of concept study, we explored the conceptual
      notion of shared and complementary mental models through EEG mapping of two
      brains performing a real-world interactive motor task of increasing difficulty.
      We used the recently introduced participative "juggling paradigm," and collected
      neuro-physiological and psycho-social data. We were interested in analyzing the
      between-brains coupling during a dyadic juggling task, and in exploring the
      relationship between the motor task execution, the jugglers'skill level and the
      task difficulty. We also investigated how this relationship could be mirrored in
      the coupled functional organization of the interacting brains. METHODS: To
      capture the neural schemas underlying the notion of shared and complementary
      mental models, we examined the functional connectivity patterns and hyperbrain
      features of a juggling dyad involved in cooperative motor tasks of increasing
      difficulty. Jugglers' cortical activity was measured using two synchronized 32
      channel EEG systems during dyadic juggling performed with 3, 4, 5 and 6 balls.
      Individual and hyperbrain functional connections were quantified through
      coherence maps calculated across all electrode pairs in the theta and alpha bands
      (4-8 and 8-12 Hz). Graph metrics were used to typify the global topology and
      efficiency of the functional networks for the four difficulty levels in the theta
      and alpha bands. RESULTS: Results indicated that, as task difficulty increased,
      the cortical functional organization of the more skilled juggler became
      progressively more segregated in both frequency bands, with a small-world
      organization in the theta band during easier tasks, indicative of a flow-like
      state in line with the neural efficiency hypothesis. Conversely, more integrated
      functional patterns were observed for the less skilled juggler in both frequency
      bands, possibly related to cognitive overload due to the difficulty of the task
      at hand (reinvestment hypothesis). At the hyperbrain level, a segregated
      functional organization involving areas of the visuo-attentional networks of both
      jugglers was observed in both frequency bands and for the easier task only.
      DISCUSSION: These results suggest that cooperative juggling is supported by
      integrated activity of specialized cortical areas from both brains only during
      easier tasks, whereas it relies on individual skills, mirrored in uncorrelated
      individual brain activations, during more difficult tasks. These findings suggest
      that task difficulty and jugglers' personal skills may influence the features of
      the hyperbrain network in its shared/integrative and complementary/segregative
      tendencies.

PMID- 27688971
TI  - Harvesting and chewing as constraints to forage consumption by the African
      savanna elephant (Loxodonta africana).
AB  - As a foundation for understanding the diet of African savanna elephants
      (Loxodonta africana), adult bulls and cows were observed over an annual cycle to
      determine whether harvesting (Pt ), chewing (Ct ) and handling times (Ht )
      differed across food types and harvesting methods (handling time is defined as
      the time to harvest, chew and swallow a trunkload of food). Bulls and cows were
      observed 105 and 26 times, respectively (94 and 26 individuals), with a total of
      64 h of feeding recorded across 32 vegetation types. Some food types took longer
      to harvest and chew than others, which may influence intake rate and affect
      choice of diet. The method used to gather a trunkload of food had a significant
      effect on harvesting time, with simple foraging actions being comparatively rapid
      and more difficult tasks taking longer. Handling time was constrained by chewing
      for bulls, except for the processing of roots from woody plants, which was
      limited by harvesting. Time to gather a trunkload had a greater influence on
      handling time for cows compared to bulls. Harvesting and handling times were
      longer for bulls than cows, with the sexes adopting foraging behaviors that best
      suited their energy requirements. 

PMID- 27688972
TI  - Overland movement in African clawed frogs (Xenopus laevis): a systematic review.
AB  - African clawed frogs (Xenopus laevis) are often referred to as 'purely aquatic'
      but there are many publications which suggest extensive overland movements.
      Previous reviews which considered the topic have not answered the following
      questions: (1) is there evidence for overland dispersal in native and invasive
      ranges; (2) what is the range of distances moved overland; (3) when does overland
      movement occur; and (4) is there evidence of breeding migratory behaviour? A
      systematic review was chosen to synthesise and critically analyse all literature
      on the overland movement in Xenopus laevis. Database searches resulted in 57
      documents which revealed a paucity of empirical studies, with 28 containing no
      data, and 19 having anecdotal content. Overwhelming evidence shows that both
      native and invasive populations of X. laevis move overland, with well documented
      examples for several other members of the genus (X. borealis, X. gilli, X.
      muelleri, X. fraseriand X. tropicalis). Reports of distances moved overland were
      from 40 m to 2 km, with no apparent difference between native and invasive
      ranges. Overland movements are not confined to wet seasons or conditions, but the
      literature suggests that moving overland does not occur in the middle of the day.
      Migrations to temporary water-bodies for breeding have been suggested, but
      without any corroborating data. 

PMID- 27688973
TI  - New beaked whales from the late Miocene of Peru and evidence for convergent
      evolution in stem and crown Ziphiidae (Cetacea, Odontoceti).
AB  - The Ziphiidae (beaked whales) represent a large group of open-ocean odontocetes
      (toothed cetaceans), whose elusive and deep diving behavior prevents direct
      observation in their natural habitat. Despite their generally large body size,
      broad geographical distribution, and high species number, ziphiids thus remain
      poorly known. Furthermore, the evolutionary processes that have led to their
      extreme adaptations and impressive extant diversity are still poorly understood.
      Here we report new fossil beaked whales from the late Miocene of the Pisco
      Formation (southern Peru). The best preserved remains here described are referred
      to two new genera and species, the Messinian Chavinziphius maxillocristatus and
      the Tortonian Chimuziphius coloradensis, based on skull remains from two marine
      vertebrate-rich localities: Cerro Los Quesos and Cerro Colorado, respectively. C.
      maxillocristatus is medium sized retains a complete set of functional lower
      teeth, and bears robust rostral maxillary crests similar to those of the extant
      Berardius. By contrast, C. coloradensis is small and characterized by large
      triangular nasals and moderately thickened premaxillae that dorsally close the
      mesorostral groove. Both species confirm the high past diversity of Ziphiidae,
      the richest cetacean family in terms of the number of genera and species. Our new
      phylogenetic and biogeographical analyses depart markedly from earlier studies in
      dividing beaked whales into two major clades: the Messapicetus clade, which,
      along with other stem ziphiids, once dominated the southeastern Pacific and North
      Atlantic; and crown Ziphiidae, the majority of which are found in deep-water
      regions of the Southern Ocean, with possible subsequent dispersal both globally
      (Mesoplodon and Ziphius) and to the cooler waters of the northern oceans
      (Berardius and Hyperoodon). Despite this relatively clear separation, both
      lineages seem to follow similar evolutionary trends, including (1) a progressive
      reduction of dentition; (2) an increase in the compactness and thickness of the
      rostral bones; (3) similar changes in facial morphology (e.g., elevation of the
      vertex); and (4) an increase of body size. We suggest that these trends may be
      linked to a convergent ecological shift to deep diving and suction feeding. 

PMID- 27688974
TI  - Evaluation of the effectiveness of insecticide trunk injections for control of
      Latoia lepida (Cramer) in the sweet olive tree Osmanthus fragrans.
AB  - The screening of suitable insecticides is a key factor in successfully applying
      trunk injection technology to ornamental plants. In this study, six chemical
      pesticides were selected and injected into the trunks of Osmanthus fragrans to
      control the nettle caterpillar, Latoia lepida (Lepidoptera: Limacodidae), using a
      no-pressure injection system. The absorption rate of the insecticides, the leaf
      loss due to insect damage, and the mortality and frass amount of L. lepida larvae
      were evaluated after 77 and 429 days. The results showed that 4% imidacloprid +
      carbosulfan and 21% abamectin + imidacloprid + omethoate had the fastest
      conductivity and were completely absorbed into the trunkswithin14 days; however,
      the efficiencies of these insecticides in controlling L. lepidawere extremely
      low. Additionally, the treatment 10% emamectin benzoate + clothianidin and 2.5%
      emamectin benzoate was almost completely absorbed within 30 days and exhibited a
      longer duration of insecticide efficiency (>80% mortality) in the upper and lower
      leaves of the canopy. Treatment with these insecticides also resulted in
      significantly lower leaf loss and frass amounts. We conclude that emamectin
      benzoate and emamectin benzoate + clothianidin have a rapid uptake into O.
      fragrans, and are effective as insecticides over long durations. Hence, they may
      be a suitable control option for L. lepida in O. fragrans plants. 

PMID- 27688975
TI  - A genetic programming approach to oral cancer prognosis.
AB  - BACKGROUND: The potential of genetic programming (GP) on various fields has been
      attained in recent years. In bio-medical field, many researches in GP are focused
      on the recognition of cancerous cells and also on gene expression profiling data.
      In this research, the aim is to study the performance of GP on the survival
      prediction of a small sample size of oral cancer prognosis dataset, which is the
      first study in the field of oral cancer prognosis. METHOD: GP is applied on an
      oral cancer dataset that contains 31 cases collected from the Malaysia Oral
      Cancer Database and Tissue Bank System (MOCDTBS). The feature subsets that is
      automatically selected through GP were noted and the influences of this subset on
      the results of GP were recorded. In addition, a comparison between the GP
      performance and that of the Support Vector Machine (SVM) and logistic regression
      (LR) are also done in order to verify the predictive capabilities of the GP.
      RESULT: The result shows that GP performed the best (average accuracy of 83.87%
      and average AUROC of 0.8341) when the features selected are smoking, drinking,
      chewing, histological differentiation of SCC, and oncogene p63. In addition,
      based on the comparison results, we found that the GP outperformed the SVM and LR
      in oral cancer prognosis. DISCUSSION: Some of the features in the dataset are
      found to be statistically co-related. This is because the accuracy of the GP
      prediction drops when one of the feature in the best feature subset is excluded.
      Thus, GP provides an automatic feature selection function, which chooses features
      that are highly correlated to the prognosis of oral cancer. This makes GP an
      ideal prediction model for cancer clinical and genomic data that can be used to
      aid physicians in their decision making stage of diagnosis or prognosis.

PMID- 27688976
TI  - Aggressive nutrition in extremely low birth weight infants: impact on parenteral
      nutrition associated cholestasis and growth.
AB  - BACKGROUND: Parenteral nutrition associated cholestasis (PNAC) is a frequently
      observed pathology in extremely low birth weight (ELBW) infants. Its pathogenesis
      is determined by the composition and duration of parenteral nutrition (PN) as
      well as the tolerance of enteral feeds (EF). "Aggressive" nutrition is
      increasingly used in ELBW infants to improve postnatal growth. Little is known
      about the effect of "aggressive" nutrition on the incidence of PNAC. We analyzed
      the influence of implementing an "aggressive" nutritional regimen on the
      incidence of PNAC and growth in a cohort of ELBW infants. METHODS: ELBW infants
      were nourished using a "conservative" (2005-6; n = 77) or "aggressive" (2007-9; n
      = 85) nutritional regimen that differed in the composition of PN after birth as
      well as the composition and timing of advancement of EFs. We analyzed the
      incidence of PNAC (conjugated bilirubin > 1.5 mg/dl (25 umol/l)) corrected for
      confounders of cholestasis (i.e., NEC and/or gastrointestinal surgery, sepsis,
      birth weight, Z-score of birth weight, time on PN and male sex), growth until
      discharge (as the most important secondary outcome) and neonatal morbidities.
      RESULTS: The incidence of PNAC was significantly lower during the period of
      "aggressive" vs. "conservative "nutrition (27% vs. 46%, P < 0.05; adjusted OR
      0.275 [0.116-0.651], P < 0.01). Body weight (+411g), head circumference (+1 cm)
      and length (+1 cm) at discharge were significantly higher. Extra-uterine growth
      failure (defined as a Z-score difference from birth to discharge lower than -1)
      was significantly reduced for body weight (85% vs. 35%), head circumference (77%
      vs. 45%) and length (85% vs. 65%) (P < 0.05). The body mass index (BMI) at
      discharge was significantly higher (11.1 vs. 12.4) using "aggressive" nutrition
      and growth became more proportionate with significantly less infants being
      discharged below the 10th BMI percentile (44% vs. 9%), while the percentage of
      infants discharged over the 90th BMI percentile (3% vs. 5%) did not significantly
      increase. DISCUSSION: "Aggressive" nutrition of ELBW infants was associated with
      a significant decrease of PNAC and marked improvement of postnatal growth.

PMID- 27688977
TI  - Chromosomal rearrangements and protein globularity changes in Mycobacterium
      tuberculosis isolates from cerebrospinal fluid.
AB  - BACKGROUND: Meningitis is a major cause of mortality in tuberculosis (TB). It is
      not clear what factors promote central nervous system invasion and pathology but
      it has been reported that certain strains of Mycobacterium tuberculosis (Mtb)
      might have genetic traits associated with neurotropism. METHODS: In this study,
      we generated whole genome sequences of eight clinical strains of Mtb that were
      isolated from the cerebrospinal fluid (CSF) of patients presenting with
      tuberculous meningitis (TBM) in Malaysia, and compared them to the genomes of
      H37Rv and other respiratory Mtb genomes either downloaded from public databases
      or extracted from local sputum isolates. We aimed to find genomic features that
      might be distinctly different between CSF-derived and respiratory Mtb. RESULTS:
      Genome-wide comparisons revealed rearrangements (translocations, inversions,
      insertions and deletions) and non-synonymous SNPs in our CSF-derived strains that
      were not observed in the respiratory Mtb genomes used for comparison. These
      rearranged segments were rich in genes for PE (proline-glutamate)/PPE (proline
      proline-glutamate), transcriptional and membrane proteins. Similarly, most of the
      ns SNPs common in CSF strains were noted in genes encoding PE/PPE proteins.
      Protein globularity differences were observed among mycobacteria from CSF and
      respiratory sources and in proteins previously reported to be associated with TB
      meningitis. Transcription factors and other transcription regulators featured
      prominently in these proteins. Homologs of proteins associated with Streptococcus
      pneumoniae meningitis and Neisseria meningitidis virulence were identified in
      neuropathogenic as well as respiratory mycobacterial spp. examined in this study.
      DISCUSSION: The occurrence of in silico genetic differences in CSF-derived but
      not respiratory Mtb suggests their possible involvement in the pathogenesis of
      TBM. However, overall findings in this comparative analysis support the
      postulation that TB meningeal infection is more likely to be related to the
      expression of multiple virulence factors on interaction with host defences than
      to CNS tropism associated with specific genetic traits.

PMID- 27688978
TI  - Validation of picogram- and femtogram-input DNA libraries for microscale
      metagenomics.
AB  - High-throughput sequencing libraries are typically limited by the requirement for
      nanograms to micrograms of input DNA. This bottleneck impedes the microscale
      analysis of ecosystems and the exploration of low biomass samples. Current
      methods for amplifying environmental DNA to bypass this bottleneck introduce
      considerable bias into metagenomic profiles. Here we describe and validate a
      simple modification of the Illumina Nextera XT DNA library preparation kit which
      allows creation of shotgun libraries from sub-nanogram amounts of input DNA.
      Community composition was reproducible down to 100 fg of input DNA based on
      analysis of a mock community comprising 54 phylogenetically diverse Bacteria and
      Archaea. The main technical issues with the low input libraries were a greater
      potential for contamination, limited DNA complexity which has a direct effect on
      assembly and binning, and an associated higher percentage of read duplicates. We
      recommend a lower limit of 1 pg (~100-1,000 microbial cells) to ensure community
      composition fidelity, and the inclusion of negative controls to identify reagent
      specific contaminants. Applying the approach to marine surface water, pronounced
      differences were observed between bacterial community profiles of microliter
      volume samples, which we attribute to biological variation. This result is
      consistent with expected microscale patchiness in marine communities. We thus
      envision that our benchmarked, slightly modified low input DNA protocol will be
      beneficial for microscale and low biomass metagenomics. 

PMID- 27688979
TI  - CD4 cell count and CD4/CD8 ratio increase during rituximab maintenance in
      granulomatosis with polyangiitis patients.
AB  - INTRODUCTION: Rituximab (RTX) is a B cell-depleting agent approved for the
      treatment of granulomatosis with polyangiitis (GPA). RTX reduces antibody
      producing precursor plasma cells and inhibits B and T cells interaction.
      Infections related to T cell immunodeficiency are not infrequent during RTX
      treatment. Our study investigated CD4 cell count and CD4/CD8 ratio in GPA
      patients during the first two years of long-term RTX treatment. METHODS: A single
      centre cohort study of 35 patients who received median total cumulative dose of
      cyclophosphamide (CYC) of 15 g and were treated with RTX 2 g followed by
      retreatment with either 2 g once annually or 1 g biannually. Serum levels of
      total immunoglobulin (Ig) and lymphocytes subsets were recorded at RTX initiation
      and at 3, 6, 12, 18 and 24 months. Low CD4 count and inverted CD4/CD8 ratio were
      defined as CD4 < 0.3 * 10(9)/l and ratio < 1. RESULTS: The CD4 cell count and
      CD4/CD8 ratio decreased slightly following the initial RTX treatment and then
      increased gradually during maintenance treatment. While the proportion of
      patients with low CD4 cell count decreased from 43% at baseline to 18% at 24
      months, the ratio remained inverted in 40%. Oral daily prednisolone dose at
      baseline, CYC exposure and the maintenance regimen did not influence the CD4 cell
      count and ratio. Being older (p = 0.012) and having a higher CRP (p = 0.044) and
      ESR (p = 0.024) at baseline significantly increased the risk of inverted CD4/CD8
      ratio at 24 months. Inverted ratio at baseline associated with lower total Ig
      levels during the study. CONCLUSIONS: Overall, the CD4 and CD4/CD8 ratio
      increased during maintenance RTX therapy in GPA with no discernible impact of
      other immunosuppressive therapy. However the increase in CD4 was not followed by
      an increase in the CD4/CD8 ratio, especially in older patients. Inverted CD4/CD8
      ratio associated with lower Ig levels, suggesting a more profound B cell
      depleting effect of RTX with a relative increase in CD8+ lymphocytes.

PMID- 27688980
TI  - Spermatozoon ultrastructure in two monorchiid digeneans.
AB  - Spermatological characteristics of species from two monorchiid genera,
      Opisthomonorchis and Paramonorcheides, have been investigated, for the first
      time, by means of transmission electron microscopy. The ultrastructural study
      reveals that the mature spermatozoon of Opisthomonorchis dinema and
      Paramonorcheides selaris share several characters such as the presence of two
      axonemes of different lengths showing the 9+"1" pattern of the Trepaxonemata, a
      nucleus, two mitochondria, two bundles of parallel cortical microtubules,
      external ornamentation of the plasma membrane, spine-like bodies, granules of
      glycogen and similar morphologies of the anterior and posterior extremities. The
      slight differences between the male gamete of O. dinema and P. selaris are the
      length of the first axoneme and the position of the second mitochondrion. This
      study also elucidates the general morphology of the spermatozoon in all
      monorchiid species described so far, which corresponds to a unique spermatozoon
      type. Other interesting finds concern the spermatological similarities between
      monorchiid spermatozoa and the mature spermatozoon reported in the apocreadiid
      Neoapocreadium chabaudi. These similarities allow us to suggest a close
      phylogenetical relationship between the Monorchiidae and the Apocreadiidae,
      although more studies are needed, especially in the unexplored taxa. 

PMID- 27688982
TI  - Self-rated mental health and race/ethnicity in the United States: support for the
      epidemiological paradox.
AB  - This paper evaluates racial/ethnic differences in self-rated mental health for
      adults in the United States, while controlling for demographic and socioeconomic
      characteristics as well as length of stay in the country. Using data from the
      2010 National Health Interview Survey Cancer Control Supplement (NHIS-CCS),
      binomial logistic regression models are fit to estimate the association between
      race/ethnicity and poor/fair self-reported mental health among US Adults. The
      size of the analytical sample was 22,844 persons. Overall prevalence of poor/fair
      self-rated mental health was 7.72%, with lower prevalence among Hispanics
      (6.93%). Non-Hispanic blacks had the highest prevalence (10.38%). After controls
      for socioeconomic characteristics are incorporated in the models, Hispanics were
      found to have a lower probability of reporting poor/fair self-rated mental health
      in comparison to non-Hispanic whites (OR = 0.70; 95% CI [0.55-0.90]). No
      difference was found for other minority groups when compared to the reference
      group in the final model. Contrary to global self-rated health, Hispanics were
      found to have a lower probability of reporting poor/fair self-rated mental health
      in comparison to non-Hispanic whites. No difference was found for non-Hispanic
      blacks when they were compared to non-Hispanic whites. Self-rated mental health
      is therefore one case of a self-rating of health in which evidence supporting the
      epidemiological paradox is found among adults in the United States. 

PMID- 27688981
TI  - A method for high precision sequencing of near full-length 16S rRNA genes on an
      Illumina MiSeq.
AB  - BACKGROUND: The bacterial 16S rRNA gene has historically been used in defining
      bacterial taxonomy and phylogeny. However, there are currently no high-throughput
      methods to sequence full-length 16S rRNA genes present in a sample with
      precision. RESULTS: We describe a method for sequencing near full-length 16S rRNA
      gene amplicons using the high throughput Illumina MiSeq platform and test it
      using DNA from human skin swab samples. Proof of principle of the approach is
      demonstrated, with the generation of 1,604 sequences greater than 1,300 nt from a
      single Nano MiSeq run, with accuracy estimated to be 100-fold higher than
      standard Illumina reads. The reads were chimera filtered using information from a
      single molecule dual tagging scheme that boosts the signal available for chimera
      detection. CONCLUSIONS: This method could be scaled up to generate many thousands
      of sequences per MiSeq run and could be applied to other sequencing platforms.
      This has great potential for populating databases with high quality, near full
      length 16S rRNA gene sequences from under-represented taxa and environments and
      facilitates analyses of microbial communities at higher resolution.

PMID- 27688984
TI  - Characteristics of the Contrast Enema Do Not Predict an Effective Bowel
      Management Regimen for Patients with Constipation or Fecal Incontinence.
AB  - BACKGROUND: A bowel management program using large volume enemas may be required
      for children with anorectal malformations (ARM), Hirschsprung's disease (HD),
      severe medically refractive idiopathic constipation (IC), and other conditions. A
      pretreatment contrast enema is often obtained. We sought to determine if the
      contrast enema findings could predict a final enema regimen. METHODS: A
      retrospective review was performed at a tertiary care children's hospital from
      2011 to 2014 to identify patients treated with enemas in our bowel management
      program. Patient characteristics, contrast enema findings (including volume to
      completely fill the colon), and final enema regimen were collected. RESULTS:
      Eighty-three patients were identified (37 ARM, 7 HD, 34 IC, and 5 other). Age
      ranged from 10 months to 24 years, and weight ranged from 6.21 kg to 95.6 kg at
      the time bowel management was initiated. Linear regression showed contrast enema
      volume was of limited value in predicting effective therapeutic saline enema
      volume (R(2 )= 0.21). The addition of diagnosis, colon dilation, and contrast
      retention on plain x-ray the day after the contrast enema moderately improved the
      predictive ability of the contrast enema (R(2 )= 0.35). Median final effective
      enema volume was 22 mL/kg (range: 5 - 48 mL/kg). CONCLUSIONS: We were unable to
      demonstrate a correlation with contrast enema findings and the effective enema
      volume. However, no patient required a daily enema volume greater than 48 mL/kg
      to stay clean.

PMID- 27688983
TI  - Effects of grip force on median nerve deformation at different wrist angles.
AB  - The present study investigated the effects of grip on changes in the median nerve
      cross-sectional area (MNCSA) and median nerve diameter in the radial-ulnar
      direction (D1) and dorsal-palmar direction (D2) at three wrist angles. Twenty
      nine healthy participants (19 men [mean age, 24.2 +/- 1.6 years]; 10 women [mean
      age, 24.0 +/- 1.6 years]) were recruited. The median nerve was examined at the
      proximal carpal tunnel region in three grip conditions, namely finger relaxation,
      unclenched fist, and clenched fist. Ultrasound examinations were performed in the
      neutral wrist position (0 degrees ), at 30 degrees wrist flexion, and at 30
      degrees wrist extension for both wrists. The grip condition and wrist angle
      showed significant main effects (p < 0.01) on the changes in the MNCSA, D1, and
      D2. Furthermore, significant interactions (p < 0.01) were found between the grip
      condition and wrist angle for the MNCSA, D1, and D2. In the neutral wrist
      position (0 degrees ), significant reductions in the MNCSA, D1, and D2 were
      observed when finger relaxation changed to unclenched fist and clenched fist
      conditions. Clenched fist condition caused the highest deformations in the median
      nerve measurements (MNCSA, approximately -25%; D1, -13%; D2, -12%). The MNCSA was
      significantly lower at 30 degrees wrist flexion and 30 degrees wrist extension
      than in the neutral wrist position (0 degrees ) at unclenched fist and clenched
      fist conditions. Notably, clenched fist condition at 30 degrees wrist flexion
      showed the highest reduction of the MNCSA (-29%). In addition, 30 degrees wrist
      flexion resulted in a lower D1 at clenched fist condition. In contrast, 30
      degrees wrist extension resulted in a lower D2 at both unclenched fist and
      clenched fist conditions. Our results suggest that unclenched fist and clenched
      fist conditions cause reductions in the MNCSA, D1, and D2. More importantly,
      unclenched fist and clenched fist conditions at 30 degrees wrist flexion and 30
      degrees wrist extension can lead to further deformation of the median nerve. 

PMID- 27688985
TI  - Cardiovascular Disease Death Before Age 65 in 168 Countries Correlated
      Statistically with Biometrics, Socioeconomic Status, Tobacco, Gender, Exercise,
      Macronutrients, and Vitamin K.
AB  - BACKGROUND: Nutrition researchers recently recognized that deficiency of vitamin
      K2 (menaquinone: MK-4-MK-13) is widespread and contributes to cardiovascular
      disease (CVD). The deficiency of vitamin K2 or vitamin K inhibition with warfarin
      leads to calcium deposition in the arterial blood vessels. METHODS: Using
      publicly available sources, we collected food commodity availability data and
      derived nutrient profiles including vitamin K2 for people from 168 countries. We
      also collected female and male cohort data on early death from CVD (ages 15-64
      years), insufficient physical activity, tobacco, biometric CVD risk markers,
      socioeconomic risk factors for CVD, and gender. The outcome measures included (1)
      univariate correlations of early death from CVD with each risk factor, (2) a
      multiple regression-derived formula relating early death from CVD (dependent
      variable) to macronutrient profile, vitamin K1 and K2 and other risk factors
      (independent variables), (3) for each risk factor appearing in the multiple
      regression formula, the portion of CVD risk attributable to that factor, and (4)
      similar univariate and multivariate analyses of body mass index (BMI), fasting
      blood sugar (FBS) (simulated from diabetes prevalence), systolic blood pressure
      (SBP), and cholesterol/ HDL-C ratio (simulated from serum cholesterol) (dependent
      variables) and dietary and other risk factors (independent variables). RESULTS:
      Female and male cohorts in countries that have vitamin K2 < 5ug per 2000 kcal/day
      per capita (n = 70) had about 2.2 times the rate of early CVD deaths as people in
      countries with > 24 ug/day of vitamin K2 per 2000 kcal/day (n = 72). A multiple
      regression-derived formula relating early death from CVD to dietary nutrients and
      other risk factors accounted for about 50% of the variance between cohorts in
      early CVD death. The attributable risks of the variables in the CVD early death
      formula were: too much alcohol (0.38%), too little vitamin K2 (6.95%), tobacco
      (6.87%), high blood pressure (9.01%), air pollution (9.15%), early childhood
      death (3.64%), poverty (7.66%), and male gender (6.13%). CONCLUSIONS: Worldwide
      dietary vitamin K2 data derived from food commodities add much understanding to
      the analysis of CVD risk factors and the etiology of CVD. Vitamin K2 in food
      products should be systematically quantified. Public health programs should be
      considered to increase the intake of vitamin K2-containing fermented plant foods
      such as sauerkraut, miso, and natto.

PMID- 27688986
TI  - Pulmonary Alveolar Microlithiasis "Stone Lungs": A Case of Clinico-Radiological
      Dissociation.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare infiltrative lung disease
      characterized by deposition of spherical calcium phosphate microliths called
      calcospherites within the alveoli. PAM was first described by Friedrich in 1856
      and then by Harbitz in 1918. The disease pathogenesis is based on mutations in
      the SLC34A2 gene that encodes for the Type IIb sodium-phosphate cotransporter.
      The majority of the patients are diagnosed at an early age, usually between the
      ages of 20 and 40 years. The hallmark of this disease is a striking dissociation
      between the radiological findings and the mild clinical symptoms.  We report a
      case of 35-year-old woman who presented post-motor vehicle accident with back
      pain and with minimal dyspnea on exertion. The final diagnosis was made after
      computed tomography and lung biopsy. The present case exhibits the remarkable
      clinico-radiological dissociation with complete calcification of the lungs on
      radiographic images with a relatively mild clinical presentation. 

PMID- 27688987
TI  - Hypoplastic Internal Carotid Artery Co-Presenting with Neurofibromatosis and
      Intracranial Masses.
AB  - Neurofibromatosis type 1 (NF1) is associated with systemic vascular disease, and
      it can also affect intracranial vasculature in a small percentage of patients.
      Very rarely, NF1 may co-present with hypoplasia of the internal carotid artery
      (ICA). Prior reports have documented NF1 with bilateral optic gliomas and a
      unilateral hypoplastic internal carotid artery; however, we report a case with
      the aforementioned findings in addition to a right-sided lentiform mass. This
      case report further suggests a common congenital pathway related to neurofibromin
      loss of function resulting in both nerve sheath tumors and cerebrovascular
      anomalies. 

PMID- 27688988
TI  - Chronic Pulmonary Histoplasmosis and its Clinical Significance: an Under-reported
      Systemic Fungal Disease.
AB  - Histoplasmosis is a systemic fungal mycosis caused by Histoplasma capsulatum. It
      is a dimorphic fungus which lives as a saprophyte in the environment and
      occasionally infects immunosuppressed people. H capsulatum is a ubiquitous fungus
      present throughout the globe and is more common in the temperate world. Human
      infection with H capsulatum occurs through respiratory route by inhalation of
      spores present in the air as droplet nuclei. Pulmonary histoplasmosis is
      difficult to diagnose, more so in the regions where tuberculosis is endemic, and
      many infected patients remain asymptomatic. In the case of immunosuppression,
      clinical symptoms of pulmonary infection may be seen along with chances of
      dissemination. We report a case of chronic pulmonary histoplasmosis in an
      immunocompetent individual. 

PMID- 27688989
TI  - Comparison of Pain Scores in Postoperative Patients: Intravenous Morphine Patient
      Controlled Analgesia vs Iontophoretic Transdermal Fentanyl.
AB  - Postoperative management of pain has traditionally utilized intravenous (IV)
      morphine for pain control. An alternative approach to the invasive patient
      controlled analgesia (PCA) system is the administration of transdermal
      analgesics, such as fentanyl. In 2006 the Food and Drug Administration (FDA)
      approved the fentanyl hydrochloride (fentanyl HCl) iontophoretic transdermal
      system (ITS), which utilizes iontophoretic technology to produce a controlled
      electrical current that propels ionized fentanyl molecules into the systemic
      vasculature. Transdermal fentanyl has been shown to be equivalent or superior to
      IV morphine PCA in a variety of postoperative settings with patients experiencing
      decreased pain scores and a favorable side effect profile. 

PMID- 27688990
TI  - Seizure Prophylaxis in Patients with Traumatic Brain Injury: A Single-Center
      Study.
AB  - The use of prophylactic anticonvulsants to prevent early post-traumatic seizures
      (PTSs) is recommended but inconsistently employed in patients with traumatic
      brain injury (TBI). The authors evaluated outcomes associated with prophylaxis
      administration in patients with TBI at a Level 1 trauma center. All patients
      admitted with TBI from October 2007 through May 2012 were included. Our primary
      outcome was the incidence of early PTSs. Secondary outcomes included mortality,
      length of hospital and intensive care unit (ICU) stays, and incidence of late
      seizures. Of the 2,111 patients with TBI, 557 (26.4%) received seizure
      prophylaxis and 1,554 (73.6%) did not. Two early PTSs occurred in the prophylaxis
      group (0.4%), whereas 21 occurred in the non-prophylaxis group (1.4%) (p = 0.05).
      The overall mortality rate was higher in patients who received prophylaxis (14.2%
      vs. 6.2%; p < 0.001), and the mean hospital length of stay (LOS) was longer (6.8
      +/- 6.9 vs. 3.8 +/- 5 days; p < 0.001). In patients with severe and moderate TBI,
      the rate of prophylaxis administration was approximately half, whereas
      significantly fewer patients with mild TBI received prophylaxis than did not
      (20.2% vs 79.8%, p < 0.001). Lower Glasgow Coma Scale (GCS) score and longer
      hospital LOS were associated with early PTS (p = 0.008 for both comparisons), but
      sex and age were not. Brain hemorrhage was present in 78.3% of those patients who
      experienced early seizures. In our cohort, patients who received seizure
      prophylaxis had a lower GCS score, higher overall mortality rate, longer LOS, and
      more frequent ICU admissions, suggesting that patients who received prophylaxis
      were likely more severely injured. 

PMID- 27688991
TI  - Correction: Generalized Tetanus Initially Presenting with Dysmasesis.
AB  - [This corrects the article DOI: 10.7759/cureus.644.].

PMID- 27688992
TI  - Interventions for drug-using offenders with co-occurring mental health problems:
      a systematic review and economic appraisal.
AB  - BACKGROUND: Drug-using offenders with co-occurring mental health problems are
      common in the criminal justice system. A combination of drug use and mental
      health problems makes people more likely to be arrested for criminal involvement
      after release compared to offenders without a mental health problem. Previous
      research has evaluated interventions aimed broadly at those with a drug problem
      but rarely with drug use and mental health problems. This systematic review
      considers the effectiveness of interventions for drug-using offenders with co
      occurring mental health problems. METHODS: We searched 14 electronic
      bibliographic databases up to May 2014 and five Internet resources. The review
      included randomised controlled trials designed to reduce, eliminate, or prevent
      relapse of drug use and/or criminal activity. Data were reported on drug and
      crime outcomes, the identification of mental health problems, diagnoses and
      resource information using the Drummond checklist. The systematic review used
      standard methodological procedures as prescribed by the Cochrane collaboration.
      RESULTS: Eight trials with 2058 participants met the inclusion criteria. These
      evaluated: case management (RR, 1.05, 95 % CI 0.90 to 1.22, 235 participants),
      motivational interviewing and cognitive skills, (MD-7.42, 95 % CI-0.20.12 to
      5.28, 162 participants) and interpersonal psychotherapy (RR 0.67, 95 % CI 0.3 to
      1.5, 38 participants). None of these trials reported significant reductions in
      self-report drug misuse or crime. Four trials evaluating differing therapeutic
      community models showed reductions in re-incarceration (RR 0.28, 95 % CI 0.13 to
      0.63, 139 participants) but not re-arrest (RR 1.65, 95 % CI 0.83 to 3.28, 370
      participants) or self-report drug use (RR 0.73, 95 % CI 0.53 to 1.01, 370
      participants). Mental health problems were identified across the eight trials and
      17 different diagnoses were described. Two trials reported some resource
      information suggesting a cost-beneficial saving when comparing therapeutic
      communities to a prison alternative. CONCLUSIONS: Overall, the studies showed a
      high degree of variation, warranting a degree of caution in the interpretation of
      the magnitude of effect and direction of benefit for treatment outcomes.
      Specifically, tailored interventions are required to assess the effectiveness of
      interventions for drug-using offenders with co-occurring mental health problems.

PMID- 27688994
TI  - Cellular Star Trek: A laser-based shuttle transfers mitochondria into cells.

PMID- 27688993
TI  - Participation in the special supplemental nutrition program for women, infants,
      and children is not associated with early childhood socioemotional development:
      Results from a longitudinal cohort study.
AB  - Socioemotional development in early childhood has long-term impacts on health
      status and social outcomes, and racial and socioeconomic disparities in
      socioemotional skills emerge early in life. The Special Supplemental Nutrition
      Program for Women, Infants, and Children (WIC) is an early childhood nutrition
      intervention with the potential to ameliorate these disparities. Our objective
      was to assess the impact of WIC on early socioemotional development in a
      longitudinal study. We examined the association between WIC participation and
      scores on the Brief Infant Toddler Social Emotional Assessment (BITSEA) in 327
      predominantly African American mother-child dyads who were participants in the
      longitudinal Conditions Affecting Neurocognitive Development in Early Life
      (CANDLE) Study (Memphis, TN). To account for selection bias, we used within-child
      fixed effects to model the variability in each child's BITSEA scores over two
      measurement occasions (ages 12 and 24 months). Final models were adjusted for
      time-varying characteristics including child age, maternal stress, mental health,
      child abuse potential, marital status, and food stamp participation. In fully
      adjusted models, we found no statistically significant effect of WIC on change in
      socioemotional development (beta = 0.22 [SD = 0.39] and beta = - 0.58 [SD = 0.79]
      for BITSEA Competence and Problem subdomains, respectively). Using rigorous
      methods and a longitudinal study design, we found no significant association
      between WIC and socioemotional development in a high needs population. This
      finding suggests that early childhood interventions that more specifically target
      socioemotional development are necessary if we are to reduce racial disparities
      in socioemotional skills and prevent poor social and health outcomes across the
      life course. 

PMID- 27688995
TI  - alpha-Melanocyte stimulating hormone promotes muscle glucose uptake via
      melanocortin 5 receptors.
AB  - OBJECTIVE: Central melanocortin pathways are well-established regulators of
      energy balance. However, scant data exist about the role of systemic melanocortin
      peptides. We set out to determine if peripheral alpha-melanocyte stimulating
      hormone (alpha-MSH) plays a role in glucose homeostasis and tested the hypothesis
      that the pituitary is able to sense a physiological increase in circulating
      glucose and responds by secreting alpha-MSH. METHODS: We established glucose
      stimulated alpha-MSH secretion using humans, non-human primates, and mouse
      models. Continuous alpha-MSH infusions were performed during glucose tolerance
      tests and hyperinsulinemic-euglycemic clamps to evaluate the systemic effect of
      alpha-MSH in glucose regulation. Complementary ex vivo and in vitro techniques
      were employed to delineate the direct action of alpha-MSH via the melanocortin 5
      receptor (MC5R)-PKA axis in skeletal muscles. Combined treatment of non
      selective/selective phosphodiesterase inhibitor and alpha-MSH was adopted to
      restore glucose tolerance in obese mice. RESULTS: Here we demonstrate that
      pituitary secretion of alpha-MSH is increased by glucose. Peripheral alpha-MSH
      increases temperature in skeletal muscles, acts directly on soleus and
      gastrocnemius muscles to significantly increase glucose uptake, and enhances
      whole-body glucose clearance via the activation of muscle MC5R and protein kinase
      A. These actions are absent in obese mice, accompanied by a blunting of alpha-MSH
      induced cAMP levels in skeletal muscles of obese mice. Both selective and non
      selective phosphodiesterase inhibition restores alpha-MSH induced skeletal muscle
      glucose uptake and improves glucose disposal in obese mice. CONCLUSION: These
      data describe a novel endocrine circuit that modulates glucose homeostasis by
      pituitary alpha-MSH, which increases muscle glucose uptake and thermogenesis
      through the activation of a MC5R-PKA-pathway, which is disrupted in obesity.

PMID- 27688996
TI  - Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited
      neurons.
AB  - OBJECTIVE: Brain regulation of glucose homeostasis is sexually dimorphic;
      however, the impact sex hormones have on specific neuronal populations within the
      ventromedial hypothalamic nucleus (VMN), a metabolically sensitive brain region,
      has yet to be fully characterized. Glucose-excited (GE) and -inhibited (GI)
      neurons are located throughout the VMN and may play a critical role in glucose
      and energy homeostasis. Within the ventrolateral portion of the VMN (VL-VMN),
      glucose sensing neurons and estrogen receptor (ER) distributions overlap. We
      therefore tested the hypothesis that VL-VMN glucose sensing neurons were sexually
      dimorphic and regulated by 17beta-estradiol (17betaE). METHODS:
      Electrophysiological recordings of VL-VMN glucose sensing neurons in brain slices
      isolated from age- and weight-matched female and male mice were performed in the
      presence and absence of 17betaE. RESULTS: We found a new class of VL-VMN GI
      neurons whose response to low glucose was transient despite continued exposure to
      low glucose. Heretofore, we refer to these newly identified VL-VMN GI neurons as
      'adapting' or AdGI neurons. We found a sexual dimorphic response to low glucose,
      with male nonadapting GI neurons, but not AdGI neurons, responding more robustly
      to low glucose than those from females. 17betaE blunted the response of both
      nonadapting GI and AdGI neurons to low glucose in both males and females, which
      was mediated by activation of estrogen receptor beta and inhibition of AMP
      activated kinase. In contrast, 17betaE had no impact on GE or non-glucose sensing
      neurons in either sex. CONCLUSION: These data suggest sex differences and
      estrogenic regulation of VMN hypothalamic glucose sensing may contribute to the
      sexual dimorphism in glucose homeostasis.

PMID- 27688997
TI  - The satiating hormone amylin enhances neurogenesis in the area postrema of adult
      rats.
AB  - OBJECTIVE: Adult neurogenesis in the subgranular zone and subventricular zone is
      generally accepted, but its existence in other brain areas is still
      controversial. Circumventricular organs, such as the area postrema (AP) have
      recently been described as potential neurogenic niches in the adult brain. The AP
      is the major site of action of the satiating hormone amylin. Amylin has been
      shown to promote the formation of neuronal projections originating from the AP in
      neonatal rodents but the role of amylin in adult neurogenesis remains unknown.
      METHODS: To test this, we first performed an RNA-sequencing of the AP of adult
      rats acutely injected with either amylin (20 MUg/kg), amylin plus the amylin
      receptor antagonist AC187 (500 MUg/kg) or vehicle. Second, animals were
      subcutaneously equipped with minipumps releasing either amylin (50 MUg/kg/day) or
      vehicle for 3 weeks to assess cell proliferation and differentiation with the 5'
      bromo-2-deoxyuridine (BrdU) technique. RESULTS: Acute amylin injections affected
      genes involved in pathways and processes that control adult neurogenesis. Amylin
      consistently upregulated NeuroD1 transcript and protein in the adult AP, and this
      effect was blocked by the co-administration of AC187. Further, chronic amylin
      treatment increased the number of newly proliferated AP-cells and significantly
      promoted their differentiation into neurons rather than astrocytes. CONCLUSION:
      Our findings revealed a novel role of the satiating hormone amylin in promoting
      neurogenesis in the AP of adult rats.

PMID- 27688998
TI  - Defining a novel leptin-melanocortin-kisspeptin pathway involved in the metabolic
      control of puberty.
AB  - OBJECTIVE: Puberty is a key developmental phenomenon highly sensitive to
      metabolic modulation. Worrying trends of changes in the timing of puberty have
      been reported in humans. These might be linked to the escalating prevalence of
      childhood obesity and could have deleterious impacts on later (cardio-metabolic)
      health, but their underlying mechanisms remain unsolved. The neuropeptide alpha
      MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating
      the actions of leptin and likely participates in the control of reproduction.
      However, its role in the metabolic regulation of puberty and interplay with
      kisspeptin, an essential puberty-regulating neuropeptide encoded by Kiss1, remain
      largely unknown. We aim here to unveil the potential contribution of central
      alpha-MSH signaling in the metabolic control of puberty by addressing its role in
      mediating the pubertal effects of leptin and its potential interaction with
      kisspeptin. METHODS: Using wild type and genetically modified rodent models, we
      implemented pharmacological studies, expression analyses, electrophysiological
      recordings, and virogenetic approaches involving DREADD technology to selectively
      inhibit Kiss1 neurons, in order to interrogate the physiological role of a
      putative leptin->alpha-MSH->kisspeptin pathway in the metabolic control of
      puberty. RESULTS: Stimulation of central alpha-MSH signaling robustly activated
      the reproductive axis in pubertal rats, whereas chronic inhibition of
      melanocortin receptors MC3/4R, delayed puberty, and prevented the permissive
      effect of leptin on puberty onset. Central blockade of MC3/4R or genetic
      elimination of kisspeptin receptors from POMC neurons did not affect kisspeptin
      effects. Conversely, congenital ablation of kisspeptin receptors or inducible,
      DREADD-mediated inhibition of arcuate nucleus (ARC) Kiss1 neurons resulted in
      markedly attenuated gonadotropic responses to MC3/4R activation. Furthermore,
      close appositions were observed between POMC fibers and ARC Kiss1 neurons while
      blockade of alpha-MSH signaling suppressed Kiss1 expression in the ARC of
      pubertal rats. CONCLUSIONS: Our physiological, virogenetic, and functional
      genomic studies document a novel alpha-MSH->kisspeptin->GnRH neuronal signaling
      pathway involved in transmitting the permissive effects of leptin on pubertal
      maturation, which is relevant for the metabolic (and, eventually,
      pharmacological) regulation of puberty onset.

PMID- 27688999
TI  - Mechanisms underlying prorenin actions on hypothalamic neurons implicated in
      cardiometabolic control.
AB  - BACKGROUND: Hypertension and obesity are highly interrelated diseases, being
      critical components of the metabolic syndrome. Despite the growing prevalence of
      this syndrome in the world population, efficient therapies are still missing.
      Thus, identification of novel targets and therapies are warranted. An enhanced
      activity of the hypothalamic renin-angiotensin system (RAS), including the
      recently discovered prorenin (PR) and its receptor (PRR), has been implicated as
      a common mechanism underlying aberrant sympatho-humoral activation that
      contributes to both metabolic and cardiovascular dysregulation in the metabolic
      syndrome. Still, the identification of precise neuronal targets, cellular
      mechanisms and signaling pathways underlying PR/PRR actions in cardiovascular-
      and metabolic related hypothalamic nuclei remain unknown. METHODS AND RESULTS:
      Using a multidisciplinary approach including patch-clamp electrophysiology, live
      calcium imaging and immunohistochemistry, we aimed to elucidate cellular
      mechanisms underlying PR/PRR actions within the hypothalamic supraoptic (SON) and
      paraventricular nucleus (PVN), key brain areas previously involved in
      cardiometabolic regulation. We show for the first time that PRR is expressed in
      magnocellular neurosecretory cells (MNCs), and to a lesser extent, in
      presympathetic PVN neurons (PVNPS). Moreover, we show that while PRR activation
      efficiently stimulates the firing activity of both MNCs and PVNPS neurons, these
      effects involved AngII-independent and AngII-dependent mechanisms, respectively.
      In both cases however, PR excitatory effects involved an increase in
      intracellular Ca(2+) levels and a Ca(2+)-dependent inhibition of a voltage-gated
      K(+) current. CONCLUSIONS: We identified novel neuronal targets and cellular
      mechanisms underlying PR/PRR actions in critical hypothalamic neurons involved in
      cardiometabolic regulation. This fundamental mechanistic information regarding
      central PR/PRR actions is essential for the development of novel RAS-based
      therapeutic targets for the treatment of cardiometabolic disorders in obesity and
      hypertension.

PMID- 27689000
TI  - Reprogramming the body weight set point by a reciprocal interaction of
      hypothalamic leptin sensitivity and Pomc gene expression reverts extreme obesity.
AB  - OBJECTIVE: A major challenge for obesity treatment is the maintenance of reduced
      body weight. Diet-induced obese mice are resistant to achieving normoweight once
      the obesogenic conditions are reversed, in part because lowered circulating
      leptin leads to a reduction in metabolic rate and a rebound of hyperphagia that
      defend the previously elevated body weight set point. Because hypothalamic POMC
      is a central leptin target, we investigated whether changes in circulating leptin
      modify Pomc expression to maintain normal energy balance in genetically
      predisposed obese mice. METHODS: Mice with reversible Pomc silencing in the
      arcuate nucleus (ArcPomc (-/-)) become morbidly obese eating low-fat chow. We
      measured body composition, food intake, plasma leptin, and leptin sensitivity in
      ArcPomc (-/-) mice weight-matched to littermate controls by calorie restriction,
      either from weaning or after developing obesity. Pomc was reactivated by
      tamoxifen-dependent Cre recombinase transgenes. Long acting PASylated leptin was
      administered to weight-reduced ArcPomc (-/-) mice to mimic the super-elevated
      leptin levels of obese mice. RESULTS: ArcPomc (-/-) mice had increased adiposity
      and leptin levels shortly after weaning. Despite chronic calorie restriction to
      achieve normoweight, ArcPomc (-/-) mice remained moderately hyperleptinemic and
      resistant to exogenous leptin's effects to reduce weight and food intake.
      However, subsequent Pomc reactivation in weight-matched ArcPomc (-/-) mice
      normalized plasma leptin, leptin sensitivity, adiposity, and food intake. In
      contrast, extreme hyperleptinemia induced by PASylated leptin blocked the full
      restoration of hypothalamic Pomc expression in calorie restricted ArcPomc (-/-)
      mice, which consequently regained 30% of their lost body weight and attained a
      metabolic steady state similar to that of tamoxifen treated obese ArcPomc (-/-)
      mice. CONCLUSIONS: Pomc reactivation in previously obese, calorie-restricted
      ArcPomc (-/-) mice normalized energy homeostasis, suggesting that their body
      weight set point was restored to control levels. In contrast, massively obese and
      hyperleptinemic ArcPomc (-/-) mice or those weight-matched and treated with
      PASylated leptin to maintain extreme hyperleptinemia prior to Pomc reactivation
      converged to an intermediate set point relative to lean control and obese ArcPomc
      (-/-) mice. We conclude that restoration of hypothalamic leptin sensitivity and
      Pomc expression is necessary for obese ArcPomc (-/-) mice to achieve and sustain
      normal metabolic homeostasis; whereas deficits in either parameter set a
      maladaptive allostatic balance that defends increased adiposity and body weight.

PMID- 27689001
TI  - Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons.
AB  - OBJECTIVE: Adiponectin receptors (AdipoRs) are located on neurons of the
      hypothalamus involved in metabolic regulation - including arcuate
      proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP)
      neurons. AdipoRs play a critical role in regulating glucose and fatty acid
      metabolism by initiating several signaling cascades overlapping with Leptin
      receptors (LepRs). However, the mechanism by which adiponectin regulates cellular
      activity in the brain remains undefined. METHODS: In order to resolve this issue,
      we utilized neuron-specific transgenic mouse models to identify Pomc and NPY/AgRP
      neurons which express LepRs for patch-clamp electrophysiology experiments.
      RESULTS: We found that leptin and adiponectin synergistically activated
      melanocortin neurons in the arcuate nucleus. Conversely, NPY/AgRP neurons were
      inhibited in response to adiponectin. The adiponectin-induced depolarization of
      arcuate Pomc neurons occurred via activation of Phosphoinositide-3-kinase (PI3K)
      signaling, independent of 5' AMP-activated protein kinase (AMPK) activity.
      Adiponectin also activated melanocortin neurons at various physiological glucose
      levels. CONCLUSIONS: Our results demonstrate a requirement for PI3K signaling in
      the acute adiponectin-induced effects on the cellular activity of arcuate
      melanocortin neurons. Moreover, these data provide evidence for PI3K as a
      substrate for both leptin and adiponectin to regulate energy balance and glucose
      metabolism via melanocortin activity.

PMID- 27689002
TI  - Physiological role for leptin in the control of thermal conductance.
AB  - OBJECTIVE: To investigate the role played by leptin in thermoregulation, we
      studied the effects of physiological leptin replacement in leptin-deficient ob/ob
      mice on determinants of energy balance, thermogenesis and heat retention under 3
      different ambient temperatures. METHODS: The effects of housing at 14  degrees C,
      22  degrees C or 30  degrees C on core temperature (telemetry), energy
      expenditure (respirometry), thermal conductance, body composition, energy intake,
      and locomotor activity (beam breaks) were measured in ob/ob mice implanted
      subcutaneously with osmotic minipumps at a dose designed to deliver a
      physiological replacement dose of leptin or its vehicle-control. RESULTS: As
      expected, the hypothermic phenotype of ob/ob mice was partially rescued by
      administration of leptin at a dose that restores plasma levels into the
      physiological range. This effect of leptin was not due to increased energy
      expenditure, as cold exposure markedly and equivalently stimulated energy
      expenditure and induced activation of brown adipose tissue irrespective of leptin
      treatment. Instead, the effect of physiological leptin replacement to raise core
      body temperature of cold-exposed ob/ob mice was associated with reduced thermal
      conductance, implying a physiological role for leptin in heat conservation.
      Finally, both leptin- and vehicle-treated ob/ob mice failed to match energy
      intake to expenditure during cold exposure, resulting in weight loss.
      CONCLUSIONS: The physiological effect of leptin to reduce thermal conductance
      contributes to maintenance of core body temperature under sub-thermoneutral
      conditions.

PMID- 27689004
TI  - Impact of statistical models on the prediction of type 2 diabetes using non
      targeted metabolomics profiling.
AB  - OBJECTIVE: Characterizing specific metabolites in sub-clinical phases preceding
      the onset of type 2 diabetes to enable efficient preventive and personalized
      interventions. RESEARCH DESIGN AND METHODS: We developed predictive models of
      type 2 diabetes using two strategies. One strategy focused on the probability of
      incidence only and was based on logistic regression (MRS1); the other strategy
      accounted for the age at diagnosis of diabetes and was based on Cox regression
      (MRS2). We assessed 293 metabolites using non-targeted metabolomics in fasting
      plasma samples of 1,044 participants (including 231 incident cases over 9 years)
      used as training population; and fasting serum samples of 128 participants (64
      incident cases versus 64 controls) used as validation population. We applied a
      LASSO-based variable selection aiming at maximizing the out-of-sample area under
      the receiver operating characteristic curve (AROC) and integrated AROC. RESULTS:
      Sixteen and 17 metabolites were selected for MRS1 and MRS2, respectively, with
      AROC = 90% and 73% in the training and validation populations, respectively for
      MRS1. MRS2 had a similar performance and was significantly associated with a
      younger age of onset of type 2 diabetes (beta = -3.44 years per MRS2 SD in the
      training population, p = 1.56 * 10(-7); beta = -4.73 years per MRS2 SD in the
      validation population, p = 4.04 * 10(-3)). CONCLUSIONS: Overall, this study
      illustrates that metabolomics improves prediction of type 2 diabetes incidence of
      4.5% on top of known clinical and biological markers, reaching 90% in total AROC,
      which is considered the threshold for clinical validity, suggesting it may be
      used in targeting interventions to prevent type 2 diabetes.

PMID- 27689003
TI  - TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced
      obesity and insulin resistance via inhibition of the IP6K1 pathway.
AB  - OBJECTIVE: Obesity and type 2 diabetes (T2D) lead to various life-threatening
      diseases such as coronary heart disease, stroke, osteoarthritis, asthma, and
      neurodegeneration. Therefore, extensive research is ongoing to identify novel
      pathways that can be targeted in obesity/T2D. Deletion of the inositol
      pyrophosphate (5-IP7) biosynthetic enzyme, inositol hexakisphosphate kinase-1
      (IP6K1), protects mice from high fat diet (HFD) induced obesity (DIO) and insulin
      resistance. Yet, whether this pathway is a valid pharmacologic target in
      obesity/T2D is not known. Here, we demonstrate that TNP [N2-(m-Trifluorobenzyl),
      N6-(p-nitrobenzyl)purine], a pan-IP6K inhibitor, has strong anti-obesity and anti
      diabetic effects in DIO mice. METHODS: Q-NMR, GTT, ITT, food intake, energy
      expenditure, QRT-PCR, ELISA, histology, and immunoblot studies were conducted in
      short (2.5-week)- and long (10-week)-term TNP treated DIO C57/BL6 WT and IP6K1-KO
      mice, under various diet and temperature conditions. RESULTS: TNP, when injected
      at the onset of HFD-feeding, decelerates initiation of DIO and insulin
      resistance. Moreover, TNP facilitates weight loss and restores metabolic
      parameters, when given to DIO mice. However, TNP does not reduce weight gain in
      HFD-fed IP6K1-KO mice. TNP specifically enhances insulin sensitivity in DIO mice
      via Akt activation. TNP decelerates weight gain primarily by enhancing
      thermogenic energy expenditure in the adipose tissue. Accordingly, TNP's effect
      on body weight is partly abolished whereas its impact on glucose homeostasis is
      preserved at thermoneutral temperature. CONCLUSION: Pharmacologic inhibition of
      the inositol pyrophosphate pathway has strong therapeutic potential in obesity,
      T2D, and other metabolic diseases.

PMID- 27689006
TI  - Depot specific differences in the adipogenic potential of precursors are mediated
      by collagenous extracellular matrix and Flotillin 2 dependent signaling.
AB  - OBJECTIVE: Adipose tissue shows a high degree of plasticity, and adipocyte
      hyperplasia is an important mechanism for adipose tissue expansion. Different
      adipose depots respond differently to an increased demand for lipid storage.
      Orchestrating cellular expansion in vivo requires extracellular matrix (ECM)
      remodeling and a high degree of interaction between cells and ECM. METHODS: We
      studied decellularized primary adipose stromal cell derived ECM of different
      adipose depots and reseeded them with primary adipose precursors. We tested ECM
      effect on adipocyte differentiation and analyzed ECM composition using proteomic
      and immunohistochemical approaches to identify factors in the ECM influencing
      adipogenesis. RESULTS: We show that the ECM of an adipose depot is the major
      determinant for the differentiation capacity of primary preadipocytes. Visceral
      adipose tissue stromal cells differentiate less than subcutaneous cells, which,
      in turn, are less adipogenic than BAT-derived cells. This effect is based on the
      ECM composition of the respective depot and not dependent on the precursor
      origin. Addition of vitamin C pronounces the pro-adipogenic effects of the ECM,
      indicating the importance of collagenous ECM in mediating the effect. Using a
      proteomic global and a targeted downstream analysis, we identify Flotillin 2 as a
      protein enriched in pro-adipogenic ECM, which is involved in orchestrating ECM to
      preadipocyte signaling. CONCLUSIONS: We show that adipose tissue SVF secretes
      collagenous ECM, which directly modulates terminal differentiation of adipocyte
      precursors in a depot specific manner. These data demonstrate the importance of
      the tissue microenvironment in preadipocyte differentiation.

PMID- 27689005
TI  - Defects in muscle branched-chain amino acid oxidation contribute to impaired
      lipid metabolism.
AB  - OBJECTIVE: Plasma levels of branched-chain amino acids (BCAA) are consistently
      elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict
      T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D
      remains unclear. METHODS: To identify pathways related to insulin resistance, we
      performed comprehensive gene expression and metabolomics analyses in skeletal
      muscle from 41 humans with normal glucose tolerance and 11 with T2D across a
      range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells
      and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and
      assessed the effects of altered BCAA flux on lipid and glucose homeostasis.
      RESULTS: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation
      in muscle from insulin resistant humans. Experimental alterations in BCAA flux in
      cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in
      mice alters muscle lipid metabolism in vivo, resulting in increased muscle
      triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and
      increased body weight after high-fat feeding. CONCLUSIONS: Our data indicate that
      impaired muscle BCAA catabolism may contribute to the development of insulin
      resistance by perturbing both amino acid and fatty acid metabolism and suggest
      that targeting BCAA metabolism may hold promise for prevention or treatment of
      T2D.

PMID- 27689007
TI  - Genetic backgrounds determine brown remodeling of white fat in rodents.
AB  - OBJECTIVE: Genetic background largely contributes to the complexity of metabolic
      responses and dysfunctions. Induction of brown adipose features in white fat,
      known as brown remodeling, has been appreciated as a promising strategy to offset
      the positive energy balance in obesity and further to improve metabolism. Here we
      address the effects of genetic background on this process. METHODS: We
      investigated browning remodeling in a depot-specific manner by comparing the
      response of C57BL/6J, 129/Sv and FVB/NJ mouse strains to cold. RESULTS:
      Surprisingly, 129/Sv and FVB/NJ mice showed distinct brown remodeling features
      despite their similar resistance to metabolic disorders in comparison to the
      obesity-prone C57BL/6J mice. FVB/NJ mice demonstrated a preference of brown
      remodeling in inguinal subcutaneous white adipose tissue (iWAT), whereas 129/Sv
      mice displayed robust brown remodeling in visceral epididymal fat (eWAT). We
      further compared gene expression in different depots by RNA-sequencing and
      identified Hoxc10 as a novel "brake" of brown remodeling in iWAT. CONCLUSION:
      Rodent genetic background determines the brown remodeling of different white fat
      depots. This study provides new insights into the role of genetic variation in
      fat remodeling in susceptibility to metabolic diseases.

PMID- 27689008
TI  - Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight.
AB  - OBJECTIVE: We previously demonstrated that the handle-region peptide, a
      prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may
      improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking
      out the adipose tissue (P)RR gene would prevent weight gain and insulin
      resistance. METHODS: An adipose tissue-specific (P)RR knockout (KO) mouse was
      created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR
      gene is located on the X chromosome, hemizygous males were complete KO and had a
      more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO
      females. Therefore, we challenged the female mice with a high-fat diet (HFD) to
      uncover certain phenotypes. Mice were maintained on either diet for 9 weeks.
      RESULTS: KO mice had lower body weights compared to wild-types (WT). Only
      hemizygous male KO mice presented with lower total fat mass, higher total lean
      mass as well as smaller adipocytes compared to WT mice. Although food intake was
      similar between genotypes, locomotor activity during the active period was
      increased in both male and female KO mice. Interestingly, only male KO mice had
      increased O2 consumption and CO2 production during the entire 24-hour period,
      suggesting an increased basal metabolic rate. Although glycemia during a glucose
      tolerance test was similar, KO males as well as HFD-fed females had lower plasma
      insulin and C-peptide levels compared to WT mice, suggesting improved insulin
      sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin
      levels, suggesting that this phenotype can occur even in the absence of a
      significant reduction in adipose tissue weight, as observed in females and, thus,
      may be a specific effect related to the (P)RR. CONCLUSIONS: (P)RR may be an
      important therapeutic target for the treatment of obesity and its associated
      complications such as type 2 diabetes.

PMID- 27689009
TI  - Myocardin-related transcription factor A (MRTFA) regulates the fate of bone
      marrow mesenchymal stem cells and its absence in mice leads to osteopenia.
AB  - OBJECTIVE: Arising from common progenitors in the bone marrow, adipogenesis and
      osteogenesis are closely associated yet mutually exclusive during bone marrow
      mesenchymal stem cell (BMSC) development. Previous studies have shown that
      morphological changes can affect the early commitment of pluripotent BMSCs to the
      adipose versus osteoblastic lineage via modulation of RhoA activity. The RhoA
      pathway regulates actin polymerization to promote the incorporation of globular
      actin (G-actin) into filamentous actin (F-actin). In doing so, myocardin-related
      transcription factors (MRTFs) dissociate from bound G-actin and enter the nucleus
      to co-activate serum response factor (SRF) target gene expression. In this study,
      we investigated whether MRTFA/SRF is acting downstream of the RhoA pathway to
      regulate BMSC commitment in mice. METHODS: The effects of knocking out MRTFA on
      skeletal homeostasis was studied in MRTFA KO mice using micro-CT, QPCR and
      western blot assays. To determine how MRTFA affects the mechanisms regulating
      BMSC fate decisions, primary bone marrow stromal cells from WT and MRTFA KO mice
      as well as C3H10T1/2 cell lines were analyzed in vitro. RESULTS: Global MRTFA KO
      mice have lower whole body weight, shorter femoral and tibial lengths as well as
      significantly decreased bone mass in their femurs. BMSCs isolated from the KO
      mice show increased adipogenesis and reduced osteogenesis when compared to WT
      littermates. KO mice, particularly females, develop osteopenia with age, and this
      was enhanced by a high fat diet. Over-expression of MRTFA or SRF enhances
      osteogenesis in CH310T1/2 cell lines. Sca1(+), CD45(-) cells from KO marrow
      express lower amounts of smooth muscle actin (SMA) and TAZ/YAP target genes
      compared to WT counterparts. CONCLUSION: This study identified MRTFA as a novel
      regulator of skeletal homeostasis by regulating the balance between adipogenic
      and osteogenic differentiation of BMSCs. We propose that MRTFA promotes the
      osteogenic activity of TAZ/YAP by maintaining SMA production in BMSCs.

PMID- 27689010
TI  - Knockdown of ATP citrate lyase in pancreatic beta cells does not inhibit insulin
      secretion or glucose flux and implicates the acetoacetate pathway in insulin
      secretion.
AB  - OBJECTIVE: Glucose-stimulated insulin secretion in pancreatic beta cells requires
      metabolic signals including the generation of glucose-derived short chain acyl
      CoAs in the cytosol from mitochondrially-derived metabolites. One concept of
      insulin secretion is that ATP citrate lyase generates short chain acyl-CoAs in
      the cytosol from mitochondrially-derived citrate. Of these, malonyl-CoA, is
      believed to be an important signal in insulin secretion. Malonyl-CoA is also a
      precursor for lipids. Our recent evidence suggested that, in the mitochondria of
      beta cells, glucose-derived pyruvate can be metabolized to acetoacetate that is
      exported to the cytosol and metabolized to the same short chain acyl-CoAs and
      fatty acids that can be derived from citrate. We tested for redundancy of the
      citrate pathway. METHODS: We inhibited ATP citrate lyase activity using
      hydroxycitrate as well as studying a stable cell line generated with shRNA
      knockdown of ATP citrate lyase in the pancreatic beta cell line INS-1 832/13.
      RESULTS: In both instances glucose-stimulated insulin release was not inhibited.
      Mass spectrometry analysis showed that the flux of carbon from [U-(13)C]glucose
      and/or [U-(13)C]alpha-ketoisocaproic acid (KIC) into short chain acyl-CoAs in
      cells with hydroxycitrate-inhibited ATP citrate lyase or in the cell line with
      stable severe (>90%) shRNA knockdown of ATP citrate lyase was similar to the
      controls. Both (13)C-glucose and (13)C-KIC introduced substantial (13)C labeling
      into acetyl-CoA, malonyl-CoA, and HMG-CoA under both conditions. Glucose flux
      into fatty acids was not affected by ATP citrate lyase knockdown. CONCLUSION: The
      results establish the involvement of the acetoacetate pathway in insulin
      secretion in pancreatic beta cells.

PMID- 27689012
TI  - Inhibition of RORalpha/gamma suppresses atherosclerosis via inhibition of both
      cholesterol absorption and inflammation.
AB  - OBJECTIVE: Cardiovascular diseases (CVDs) are the leading cause of mortality in
      Western countries. Atherosclerosis is a multi-step inflammatory disease
      characterized at early stages by accumulation of cholesterol in the arterial wall
      followed by recruitment of immune cells. We sought to determine if
      pharmacological suppression of RORalpha/gamma activity is beneficial in treatment
      of atherosclerosis. METHODS: To identify the role of RORalpha and RORgamma in
      atherosclerosis, we used the LDL-R(-/-) mouse model of atherosclerosis placed on
      a high cholesterol diet treated with SR1001, a RORalpha/gamma inverse agonist,
      for four weeks. RESULTS: Our results demonstrate that treatment with the ROR
      inverse agonist substantially decreases plaque formation in vivo. The mechanism
      of the anti-atherogenic activity of the inhibition of RORalpha/gamma activity
      appeared to be due to targeting two distinct pathways. SR1001 treatment reduced
      plasma low density lipoprotein (LDL) level without affecting high density
      lipoprotein (HDL) via increasing intestinal cholesterol excretion. Treatment with
      SR1001 also induced an anti-atherogenic immune profile that was characterized by
      a reduction in Th17 cells and an increase in Treg and Th2 cells. Our data suggest
      that RORalpha and RORgamma play a critical role in atherosclerosis development by
      regulating at least two major pathways important in the pathology of this
      disease: cholesterol flux and inflammation. CONCLUSION: Our data suggest that
      pharmacological targeting of RORalpha/gamma may be an effective method for
      treatment of atherosclerosis offering a distinct mechanism of action relative to
      statins.

PMID- 27689011
TI  - The regulator of G-protein signaling RGS16 promotes insulin secretion and beta
      cell proliferation in rodent and human islets.
AB  - OBJECTIVE: G protein-coupled receptor (GPCR) signaling regulates insulin
      secretion and pancreatic beta cell-proliferation. While much knowledge has been
      gained regarding how GPCRs are activated in beta cells, less is known about the
      mechanisms controlling their deactivation. In many cell types, termination of
      GPCR signaling is controlled by the family of Regulators of G-protein Signaling
      (RGS). RGS proteins are expressed in most eukaryotic cells and ensure a timely
      return to the GPCR inactive state upon removal of the stimulus. The aims of this
      study were i) to determine if RGS16, the most highly enriched RGS protein in beta
      cells, regulates insulin secretion and beta-cell proliferation and, if so, ii) to
      elucidate the mechanisms underlying such effects. METHODS: Mouse and human islets
      were infected with recombinant adenoviruses expressing shRNA or cDNA sequences to
      knock-down or overexpress RGS16, respectively. 60 h post-infection, insulin
      secretion and cAMP levels were measured in static incubations in the presence of
      glucose and various secretagogues. beta-cell proliferation was measured in
      infected islets after 72 h in the presence of 16.7 mM glucose +/- somatostatin
      and various inhibitors. RESULTS: RGS16 mRNA levels are strongly up-regulated in
      islets of Langerhans under hyperglycemic conditions in vivo and ex vivo. RGS16
      overexpression stimulated glucose-induced insulin secretion in isolated mouse and
      human islets while, conversely, insulin secretion was impaired following RGS16
      knock-down. Insulin secretion was no longer affected by RGS16 knock-down when
      islets were pre-treated with pertussis toxin to inactivate Galphai/o proteins, or
      in the presence of a somatostatin receptor antagonist. RGS16 overexpression
      increased intracellular cAMP levels, and its effects were blocked by an adenylyl
      cyclase inhibitor. Finally, RGS16 overexpression prevented the inhibitory effect
      of somatostatin on insulin secretion and beta-cell proliferation. CONCLUSIONS:
      Our results identify RGS16 as a novel regulator of beta-cell function that
      coordinately controls insulin secretion and proliferation by limiting the tonic
      inhibitory signal exerted by delta-cell-derived somatostatin in islets.

PMID- 27689013
TI  - Roux-en-Y gastric bypass surgery is effective in fibroblast growth factor-21
      deficient mice.
AB  - OBJECTIVE: The mechanisms by which bariatric surgeries so effectively and
      lastingly reduce body weight and normalize metabolic dysfunction are not well
      understood. Fibroblast growth fator-21 (FGF21) is a key regulator of metabolism
      and is currently considered for treatment of obesity. Although elevated by acute
      food deprivation, it is downregulated after weight loss induced by chronic
      calorie restriction but not after Roux-en-Y gastric bypass surgery. Therefore,
      the goal of the present study was to assess the role of FGF21-signaling in the
      beneficial effects of Roux-en-Y gastric bypass surgery (RYGB). METHODS: High-fat
      diet-induced obese FGF21-deficient (FGF21(-/-)) and wildtype (WT) mice were
      subjected to RYGB, sham surgery, or caloric restriction to match body weight of
      RYGB mice. Body weight, body composition, food intake, energy expenditure,
      glucose tolerance, and insulin sensitivity, as well as plasma levels and hepatic
      mRNA expression of FGF21 were measured. RESULTS: Hepatic expression and plasma
      levels of FGF21 are higher after RYGB compared with similar weight loss induced
      by caloric restriction, suggesting that elevated FGF21 might play a role in
      preventing increased hunger and weight regain after RYGB. However, although the
      body weight differential between RYGB and sham surgery was significantly reduced
      in FGF21(-/-) mice, RYGB induced similarly sustained body weight and fat mass
      loss, initial reduction of food intake, increased energy expenditure, and
      improvements in glycemic control in FGF21(-/-) and WT mice. CONCLUSIONS: FGF21
      signaling is not a critical single factor for the beneficial metabolic effects of
      RYGB. This may open up the possibility to use FGF21 as adjuvant therapy in
      patients with ineffective bariatric surgeries.

PMID- 27689015
TI  - Sex differences in obesity development in pair-fed neuronal lipoprotein lipase
      deficient mice.
AB  - OBJECTIVE: Compared to men, postmenopausal women suffer from a disproportionate
      burden of many co-morbidities associated with obesity, e.g. cardiovascular
      disease, cancer, and dementia. The underlying mechanism for this sex difference
      is not well understood but is believed to relate to absence of the protective
      effect of estrogen through the action of estrogen receptor alpha (ERalpha) in the
      central nervous system. With the recently developed neuron-specific lipoprotein
      lipase deficient mice (NEXLPL-/-) (Wang et al., Cell Metabolism, 2011 [15]), we
      set to explore the possible role of lipid sensing in sex differences in obesity
      development. METHODS: Both male and female NEXLPL-/- mice and littermate WT
      controls were subjected to pair feeding (pf) where daily food amount given was
      adjusted according to body weight to match the food intake of ad libitum (ad) fed
      control WT mice. Food intake and body weight were measured daily, and pair
      feeding was maintained to 42 wk in male mice and to 38 wk in female mice. Various
      brain regions of the mice were harvested, and ERalpha gene expression was
      examined in both male and female NEXLPL-/- and WT control mice under both ad- and
      pf-fed conditions. RESULTS: Although both male and female NEXLPL-/- mice
      developed obesity similarly on standard chow, male NEXLPL-/- mice still developed
      obesity under with pair feeding, but on a much delayed time course, while female
      NEXLPL-/- mice were protected from extra body weight and fat mass gain compared
      to pair-fed WT control mice. Pair feeding alone induced extra fat mass gain in
      both male and female WT mice, and this was mostly driven by the reduction in
      physical activity. LPL deficiency resulted in an increase in ERalpha mRNA in the
      hypothalamus of ad-fed female mice, while pair feeding alone also resulted in an
      increase of ERalpha in both female WT control and NEXLPL-/- mice. The effect on
      increasing ERalpha by pair feeding and LPL deficiency was additive in pair-fed
      female NEXLPL-/- mice. ERalpha mRNA levels were not significantly modified in
      other brain regions examined, nor in the hypothalamus of male NEXLPL-/- mice
      compared to control mice. CONCLUSIONS: These results suggest that the mechanism
      underlying ERalpha regulation of body weight interacts with the LPL-dependent
      lipid processing in the hypothalamus in a sex specific way. ERalpha could provide
      the link between brain lipid sensing and sex differences in obesity development.
      This study has the potential important clinical implication to provide better
      management for women who suffer from obesity and obesity-related co-morbidities.

PMID- 27689016
TI  - Dynamic DNA methylation landscape defines brown and white cell specificity during
      adipogenesis.
AB  - OBJECTIVE: DNA methylation may be a stable epigenetic contributor to defining fat
      cell lineage. METHODS: We performed reduced representation bisulfite sequencing
      (RRBS) and RNA-seq to depict a genome-wide integrative view of the DNA methylome
      and transcriptome during brown and white adipogenesis. RESULTS: Our analysis
      demonstrated that DNA methylation is a stable epigenetic signature for brown and
      white cell lineage before, during, and after differentiation. We identified 31
      genes whose promoters were significantly differentially methylated between white
      and brown adipogenesis at all three time points of differentiation. Among them,
      five genes belong to the Hox family; their expression levels were anti-correlated
      with promoter methylation, suggesting a regulatory role of DNA methylation in
      transcription. Blocking DNA methylation with 5-Aza-cytidine increased the
      expression of these genes, with the most prominent effect on Hoxc10, a repressor
      of BAT marker expression. CONCLUSIONS: Our data suggest that DNA methylation may
      play an important role in lineage-specific development in adipocytes.

PMID- 27689014
TI  - Fibroblast activation protein (FAP) as a novel metabolic target.
AB  - OBJECTIVE: Fibroblast activation protein (FAP) is a serine protease belonging to
      a S9B prolyl oligopeptidase subfamily. This enzyme has been implicated in cancer
      development and recently reported to regulate degradation of FGF21, a potent
      metabolic hormone. Using a known FAP inhibitor, talabostat (TB), we explored the
      impact of FAP inhibition on metabolic regulation in mice. METHODS: To address
      this question we evaluated the pharmacology of TB in various mouse models
      including those deficient in FGF21, GLP1 and GIP signaling. We also studied the
      ability of FAP to process FGF21 in vitro and TB to block FAP enzymatic activity.
      RESULTS: TB administration to diet-induced obese (DIO) animals led to profound
      decreases in body weight, reduced food consumption and adiposity, increased
      energy expenditure, improved glucose tolerance and insulin sensitivity, and
      lowered cholesterol levels. Total and intact plasma FGF21 were observed to be
      elevated in TB-treated DIO mice but not lean animals where the metabolic impact
      of TB was significantly attenuated. Furthermore, and in stark contrast to naive
      DIO mice, the administration of TB to obese FGF21 knockout animals demonstrated
      no appreciable effect on body weight or any other measures of metabolism. In
      support of these results we observed no enzymatic degradation of human FGF21 at
      either end of the protein when FAP was inhibited in vitro by TB. CONCLUSIONS: We
      conclude that pharmacological inhibition of FAP enhances levels of FGF21 in obese
      mice to provide robust metabolic benefits not observed in lean animals, thus
      validating this enzyme as a novel drug target for the treatment of obesity and
      diabetes.

PMID- 27689017
TI  - Osteocalcin is necessary and sufficient to maintain muscle mass in older mice.
AB  - OBJECTIVE: A decrease in muscle protein turnover and therefore in muscle mass is
      a hallmark of aging. Because the circulating levels of the bone-derived hormone
      osteocalcin decline steeply during aging in mice, monkeys and humans we asked
      here whether this hormone might regulate muscle mass as mice age. METHODS: We
      examined muscle mass and strength in mice lacking osteocalcin (Ocn-/-) or its
      receptor in all cells (Gprc6a-/-) or specifically in myofibers (Gprc6a Mck -/-)
      as well as in 9 month-old WT mice receiving exogenous osteocalcin for 28 days. We
      also examined protein synthesis in WT and Gprc6a-/- mouse myotubes treated with
      osteocalcin. RESULTS: We show that osteocalcin signaling in myofibers is
      necessary to maintain muscle mass in older mice in part because it promotes
      protein synthesis in myotubes without affecting protein breakdown. We further
      show that treatment with exogenous osteocalcin for 28 days is sufficient to
      increase muscle mass of 9-month-old WT mice. CONCLUSION: This study uncovers that
      osteocalcin is necessary and sufficient to prevent age-related muscle loss in
      mice.

PMID- 27689018
TI  - The diabetes medication Canagliflozin reduces cancer cell proliferation by
      inhibiting mitochondrial complex-I supported respiration.
AB  - OBJECTIVE: The sodium-glucose transporter 2 (SGLT2) inhibitors Canagliflozin and
      Dapagliflozin are recently approved medications for type 2 diabetes. Recent
      studies indicate that SGLT2 inhibitors may inhibit the growth of some cancer
      cells but the mechanism(s) remain unclear. METHODS: Cellular proliferation and
      clonogenic survival were used to assess the sensitivity of prostate and lung
      cancer cell growth to the SGLT2 inhibitors. Oxygen consumption, extracellular
      acidification rate, cellular ATP, glucose uptake, lipogenesis, and
      phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase,
      and the p70S6 kinase were assessed. Overexpression of a protein that maintains
      complex-I supported mitochondrial respiration (NDI1) was used to establish the
      importance of this pathway for mediating the anti-proliferative effects of
      Canagliflozin. RESULTS: Clinically achievable concentrations of Canagliflozin,
      but not Dapagliflozin, inhibit cellular proliferation and clonogenic survival of
      prostate and lung cancer cells alone and in combination with ionizing radiation
      and the chemotherapy Docetaxel. Canagliflozin reduced glucose uptake,
      mitochondrial complex-I supported respiration, ATP, and lipogenesis while
      increasing the activating phosphorylation of AMPK. The overexpression of NDI1
      blocked the anti-proliferative effects of Canagliflozin indicating reductions in
      mitochondrial respiration are critical for anti-proliferative actions.
      CONCLUSION: These data indicate that like the biguanide metformin, Canagliflozin
      not only lowers blood glucose but also inhibits complex-I supported respiration
      and cellular proliferation in prostate and lung cancer cells. These observations
      support the initiation of studies evaluating the clinical efficacy of
      Canagliflozin on limiting tumorigenesis in pre-clinical animal models as well
      epidemiological studies on cancer incidence relative to other glucose lowering
      therapies in clinical populations.

PMID- 27689019
TI  - Volumetric, relaxometric and diffusometric correlates of psychotic experiences in
      a non-clinical sample of young adults.
AB  - BACKGROUND: Grey matter (GM) abnormalities are robust features of schizophrenia
      and of people at ultra high-risk for psychosis. However the extent to which
      neuroanatomical alterations are evident in non-clinical subjects with isolated
      psychotic experiences is less clear. METHODS: Individuals (mean age 20 years)
      with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified
      from a population-based cohort. All underwent T1-weighted structural, diffusion
      and quantitative T1 relaxometry MRI, to characterise GM macrostructure,
      microstructure and myelination respectively. Differences in quantitative GM
      structure were assessed using voxel-based morphometry (VBM). Binary and ordinal
      models of PEs were tested. Correlations between socioeconomic and other risk
      factors for psychosis with cortical GM measures were also computed. RESULTS: GM
      volume in the left supra-marginal gyrus was reduced in individuals with PEs
      relative to those with no PEs. The greater the severity of PEs, the greater the
      reduction in T1 relaxation rate (R1) across left temporoparietal and right pre
      frontal cortices. In these regions, R1 was positively correlated with maternal
      education and inversely correlated with general psychopathology. CONCLUSIONS: PEs
      in non-clinical subjects were associated with regional reductions in grey-matter
      volume reduction and T1 relaxation rate. The alterations in T1 relaxation rate
      were also linked to the level of general psychopathology. Follow up of these
      subjects should clarify whether these alterations predict the later development
      of an ultra high-risk state or a psychotic disorder.

PMID- 27689020
TI  - Influence of aerobic exercise training on the neural correlates of motor learning
      in Parkinson's disease individuals.
AB  - BACKGROUND: Aerobic exercise training (AET) has been shown to provide general
      health benefits, and to improve motor behaviours in particular, in individuals
      with Parkinson's disease (PD). However, the influence of AET on their motor
      learning capacities, as well as the change in neural substrates mediating this
      effect remains to be explored. OBJECTIVE: In the current study, we employed
      functional Magnetic Resonance Imaging (fMRI) to assess the effect of a 3-month
      AET program on the neural correlates of implicit motor sequence learning (MSL).
      METHODS: 20 healthy controls (HC) and 19 early PD individuals participated in a
      supervised, high-intensity, stationary recumbent bike training program (3
      times/week for 12 weeks). Exercise prescription started at 20 min (+ 5 min/week
      up to 40 min) based on participant's maximal aerobic power. Before and after the
      AET program, participants' brain was scanned while performing an implicit version
      of the serial reaction time task. RESULTS: Brain data revealed pre-post MSL
      related increases in functional activity in the hippocampus, striatum and
      cerebellum in PD patients, as well as in the striatum in HC individuals.
      Importantly, the functional brain changes in PD individuals correlated with
      changes in aerobic fitness: a positive relationship was found with increased
      activity in the hippocampus and striatum, while a negative relationship was
      observed with the cerebellar activity. CONCLUSION: Our results reveal, for the
      first time, that exercise training produces functional changes in known motor
      learning related brain structures that are consistent with improved behavioural
      performance observed in PD patients. As such, AET can be a valuable non
      pharmacological intervention to promote, not only physical fitness in early PD,
      but also better motor learning capacity useful in day-to-day activities through
      increased plasticity in motor related structures.

PMID- 27689021
TI  - Direct estimation of patient attributes from anatomical MRI based on multi-atlas
      voting.
AB  - MRI brain atlases are widely used for automated image segmentation, and in
      particular, recent developments in multi-atlas techniques have shown highly
      accurate segmentation results. In this study, we extended the role of the atlas
      library from mere anatomical reference to a comprehensive knowledge database with
      various patient attributes, such as demographic, functional, and diagnostic
      information. In addition to using the selected (heavily-weighted) atlases to
      achieve high segmentation accuracy, we tested whether the non-anatomical
      attributes of the selected atlases could be used to estimate patient attributes.
      This can be considered a context-based image retrieval (CBIR) approach, embedded
      in the multi-atlas framework. We first developed an image similarity measurement
      to weigh the atlases on a structure-by-structure basis, and then, the attributes
      of the multiple atlases were weighted to estimate the patient attributes. We
      tested this concept first by estimating age in a normal population; we then
      performed functional and diagnostic estimations in Alzheimer's disease patients.
      The accuracy of the estimated patient attributes was measured against the actual
      clinical data, and the performance was compared to conventional volumetric
      analysis. The proposed CBIR framework by multi-atlas voting would be the first
      step toward a knowledge-based support system for quantitative radiological image
      reading and diagnosis.

PMID- 27689022
TI  - Longitudinal cerebellar diffusion tensor imaging changes in posterior fossa
      syndrome.
AB  - Posterior fossa syndrome is a severe transient loss of language that frequently
      complicates resection of tumors of the cerebellum. The associated pathophysiology
      and relevant anatomy to this language deficit remains controversial. We performed
      a retrospective analysis of all cerebellar tumor resections at Seattle Children's
      Hospital from 2010 to 2015. Diffusion tensor imaging was performed on each of the
      patients as part of their clinical scan. Patients included in the study were
      divided into groups based on language functioning following resection: intact (N
      = 19), mild deficit (N = 19), and posterior fossa syndrome (N = 9). Patients with
      posterior fossa syndrome showed white matter changes evidenced by reductions in
      fractional anisotropy in the left and right superior cerebellar peduncle
      following resection, and these changes were still evident 1-year after surgery.
      These changes were greater in the superior cerebellar peduncle than elsewhere in
      the cerebellum. Prior to surgery, posterior fossa patients did not show changes
      in fractional anisotropy however differences were observed in mean and radial
      diffusivity measures in comparison to other groups which may provide a
      radiographic marker of those at greatest risk of developing post-operative
      language loss.

PMID- 27689023
TI  - Human case of bacteremia due to Streptococcus suis serotype 5 in Japan: The first
      report and literature review.
AB  - Streptococcus suis is a zoonotic pathogen that can be transferred from pigs to
      humans. The serotypes 2 and 14 are prevalent among patients with S. suis
      infections, while other serotypes (i.e., 1, 4, 5, 16, and 24) have been detected
      in rare human cases. To the best of our knowledge, the present patient handling
      with raw pork is the first human case of uncomplicated bacteremia due to S. suis
      serotype 5 in Japan. We confirmed the new sequence type 752 of this isolate.
      Virulence-associated gene profiling was performed; both sly (encoding the
      hemolysin suilysin) and mrp (encoding a muramidase-released protein) were
      detected without amplification of epf (encoding the extracellular factor). Our
      polymerase chain reaction-based results indicated that this isolate possessed
      both tet(O), the tetracycline-resistance determinant, and erm(B), the
      macrolide/lincosamide-resistance determinant. In addition, we provide the review
      of literature concerning clinical and microbiological features of four human
      cases of infection due to S. suis serotype 5. Clinicians should be aware of this
      microorganism when examining and treating patients with fever, who are handling
      raw pork or having close contact with infected pigs even if they are
      immunocompetent. 

PMID- 27689024
TI  - (123)I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and
      Application to Neurological Diseases.
AB  - (123)I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since
      its introduction to clinical cardiology and neurology practice in the 1990s.
      Neurological studies found decreased cardiac uptake of (123)I-MIBG in Lewy-body
      diseases including Parkinson's disease and dementia with Lewy bodies. Thus,
      cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although
      scintigraphic images of (123)I-MIBG can be visually interpreted, an average count
      ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative
      marker of sympathetic activity. Since H/M ratios significantly vary according to
      acquisition and processing conditions, quality control should be appropriate, and
      quantitation should be standardized. The threshold H/M ratio for differentiating
      Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to
      comparable values of medium-energy collimators. Parkinson's disease can be
      separated from various types of parkinsonian syndromes using cardiac (123)I-MIBG,
      whereas activity is decreased on images of Lewy-body diseases using both (123)I
      ioflupane for the striatum and (123)I-MIBG. Despite being a simple index, the H/M
      ratio of (123)I-MIBG uptake is reproducible and can serve as an effective tool to
      support a diagnosis of Lewy-body diseases in neurological practice. 

PMID- 27689025
TI  - Circulating Tumor Cell and Cell-free Circulating Tumor DNA in Lung Cancer.
AB  - Circulating tumor cells (CTCs) are tumor cells that are separated from the
      primary site or metastatic lesion and disseminate in blood circulation. CTCs are
      considered to be part of the long process of cancer metastasis. As a 'liquid
      biopsy', CTC molecular examination and investigation of single cancer cells
      create an important opportunity for providing an understanding of cancer biology
      and the process of metastasis. In the last decade, we have seen dramatic
      development in defining the role of CTCs in lung cancer in terms of diagnosis,
      genomic alteration determination, treatment response and, finally, prognosis
      prediction. The aims of this review are to understand the basic biology and to
      review methods of detection of CTCs that apply to the various types of solid
      tumor. Furthermore, we explored clinical applications, including treatment
      monitoring to anticipate therapy resistance as well as biomarker analysis, in the
      context of lung cancer. We also explored the potential use of cell-free
      circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer. 

PMID- 27689026
TI  - Second Generation Antipsychotics in the Treatment of Major Depressive Disorder:
      An Update.
AB  - Less than one third of patients who suffer from major depressive disorder (MDD)
      report remission following antidepressant treatments requiring more diverse
      treatment approaches. Augmentation of second generation antipsychotics (SGAs) has
      been increasingly recognized as an important treatment option. The authors have
      previously provided a comprehensive review of SGAs for the treatment of MDD in
      2013. Since then, numerous additional clinical trials have been conducted to
      investigate diverse issues regarding the utility of SGAs in MDD. Moreover, a new
      SGA, brexpiprazole, was recently approved by the Food and Drug Administration in
      July 2015 for the treatment of MDD as an augmentation agent to antidepressants.
      Thus, the aim of this study was to provide a concise update of all the available
      SGAs for the treatment of MDD, in particular on the additional clinical trials
      which have been published since 2013. 

PMID- 27689027
TI  - Targeted Cancer Therapy Using Engineered Salmonella typhimurium.
AB  - Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium,
      Salmonella, or Escherichia coli specifically colonize and proliferate inside
      tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella
      typhimurium (S. typhimurium) has been widely studied in animal cancer models and
      Phase I clinical trials in human patients. S. typhimurium genes are easily
      manipulated; thus diverse attenuated strains of S. typhimurium have been designed
      and engineered as tumor-targeting therapeutics or drug delivery vehicles that
      show both an excellent safety profile and therapeutic efficacy in mouse models.
      An attenuated strain of S. typhimurium, VNP20009, successfully targeted human
      metastatic melanoma and squamous cell carcinoma in Phase I clinical trials;
      however, the efficacy requires further refinement. Along with the characteristics
      of self-targeting, proliferation, and deep tissue penetration, the ease of
      genetic manipulation allows for the production of more attenuated strains with
      greater safety profiles and vector systems that deliver designable cargo
      molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress
      in the field of Salmonellae-mediated cancer therapy. 

PMID- 27689028
TI  - Cutaneous Melanoma in Asians.
AB  - Malignant melanoma is a rare disease in Asians but potentially the most
      aggressive form of skin cancer worldwide. It can occur in any melanocyte
      containing anatomic site. Four main cutaneous melanoma subtypes are recognized:
      lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous
      melanoma (ALM), and nodular melanoma. Generally, excessive exposure to
      ultraviolet (UV) radiation increases the risk of melanoma. The exception is ALM,
      which is the most common melanoma subtype in Asians and is not associated with UV
      radiation. ALM presents as dark brownish to black, irregular maculopatches,
      nodules, or ulcers on the palms, soles, and nails. The lesions may be
      misdiagnosed as more benign lesions, such as warts, ulcers, hematomas, foreign
      bodies, or fungal infections, especially in amelanotic acral melanomas where
      black pigments are absent. The aim of this brief review is to improve
      understanding and the rate of early detection thereby reducing mortality,
      especially regarding cutaneous melanoma in Asians. 

PMID- 27689029
TI  - Clinical Usefulness of Spectral-Domain Optical Coherence Tomography in Glaucoma
      and NAION.
AB  - The development of optical coherence tomography (OCT) has changed the clinical
      management of ophthalmic diseases by furthering the understanding of
      pathogenesis, as well as improving the monitoring of their progression and
      assisting in quantifying the response to treatment modalities in ophthalmic
      diseases. Initially, the two-dimensional configuration of the optic nerve head
      (ONH) and the thickness of the retinal nerve fiber layer (RNFL) were the main OCT
      structural parameters used in clinical management of optic nerve diseases. Now,
      with higher resolution power and faster acquisition times, the details of ONH and
      the retina including the macular area can be measured using spectral domain OCT
      (SD-OCT) with high reproducibility and increased diagnostic ability. OCT can
      provide structural information to improve the understanding and management of
      optic nerve diseases. In this review, we will briefly summarize the clinical
      applications of SD-OCT in glaucoma and nonarteritic anterior ischemic optic
      neuropathy, which are two representative optic nerve diseases. 

PMID- 27689030
TI  - Peroxisome Proliferator-Activated Receptor-gammaGene Expression and Its
      Association with Oxidative Stress in Patients with Metabolic Syndrome.
AB  - Regulation of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      gene plays an important role in controlling the metabolism of lipids and
      inflammatory processes. Therefore, it can be associated with the pathogenesis of
      metabolic syndrome (MetS). The purpose of this study was to determine the
      expression of this gene in peripheral blood mononuclear cells (PBMC) in patients
      with metabolic syndrome. Using real-time polymerase chain reaction (PCR), mRNA
      expression of PPAR-gamma was found in PBMC from 37 subjects with MetS and 30
      healthy controls. Serum levels of glucose and lipid profiles were measured. The
      total antioxidant capacity (TAC) was measured using the ferric reducing ability
      of plasma (FRAP) test. Malondialdehyde (MDA) was determined using a fluorimetric
      method. Total oxidant status (TOS) in serum was assayed according to oxidation of
      ferric to ferrous in the presence of methyl orange. Super oxide dismutase (SOD)
      activity was measured using a Randox kit. Expression of PPAR-gamma gene was
      significantly increased in patients with MetS compared to the control subjects
      (p=0.002). There was no difference in serum levels of TAC, MDA and SOD between
      the two study groups, but a significant difference was observed in the TOS
      (p=0.03). Serum levels of triglycerides and glucose were significantly higher in
      subjects with MetS. According to the results of our study, an increase in the
      expression of PPAR-gamma in subjects with MetS indicated a possible role of PPAR
      gamma in the pathogenesis of this disease. 

PMID- 27689031
TI  - Diagnosis and Management of Pediatric and Adolescent Varicocele: A Survey of
      Pediatric Urologists in Korea.
AB  - The aim of this study was to evaluate current practice patterns on diagnosis and
      management of pediatric varicoceles. Questionnaires of approaches to diagnosis
      and management of pediatric varicoceles were sent electronically to pediatric
      urologists. Of the 70 questionnaires e-mailed, 37 (53%) responded to the survey.
      10 respondents (27%) chose to operate on varicoceles, whereas 9 (24%) chose to
      observe, and 18 (49%) chose to decide upon treatment depending on the clinical
      situation. The most important indication for varicocelectomy was a decrease in
      ipsilateral testicular size (n=29, 78%) followed by testicular or scrotal pain
      (n=4, 11%) and varicocele grade (n=4, 11%). The optimal age for varicocelectomy
      was answered as 13.8+/-2.3 years mean. 32 respondents (86%) have used
      ultrasonography to aid in the diagnosis of varicoceles, and 26 respondents (70%)
      have considered repairing varicocele incidentally detected on ultrasonography. In
      an otherwise asymptomatic patient with varicocele, 17 respondents (46%)
      considered surgery for grade 3, but 15 respondents (41%) would not repair the
      varicocele. The most commonly used surgical approach was subinguinal
      microsurgical (n=19, 51%), followed by inguinal (n=9, 24%) and laparascopic (n=5,
      14%) procedures. The most commonly experienced post-operative complication was
      recurrence (n=22, 59%) followed by persistence (n=13, 35%) and hydrocele (n=10,
      27%). 28 respondents (76%) did not have long-term follow-up data including
      regarding fertility on their varicocele patients. Our survey demonstrates that
      there is lack of consensus on diagnosis and management of pediatric and
      adolescent varicoceles among pediatric urologists. A prospective randomized study
      of pediatric and adolescent varicoceles is needed to assess the outcomes and
      develop universal management guidelines. 

PMID- 27689033
TI  - Extreme Metabolic Alkalosis Caused by Gastrostomy Tube Malposition Treated Using
      Conventional Hemodialysis.

PMID- 27689032
TI  - Association between Vitamin D Status and Risk of Peripheral Arterial Disease: The
      Dong-gu Study.
AB  - Low levels of vitamin D have been associated with increased cardiovascular
      disease risk. However, few studies have evaluated the association between vitamin
      D status and peripheral arterial disease (PAD). We therefore aimed to investigate
      whether low 25-hydroxyvitamin D (25(OH)D) levels were associated with increased
      risk of PAD in the Korean population. This cross-sectional study was conducted
      among 8,960 subjects aged 50 years or older without known myocardial infarction
      or stroke. PAD was defined by an ankle brachial blood pressure index <0.9.
      Multivariate logistic regression was used to evaluate the association between
      serum 25(OH)D levels and risk of PAD. Of the 8,960 subjects, 3.0% had PAD and the
      age and sex adjusted prevalence of PAD decreased with the increasing 25(OH)D
      quartile. After adjusting for potential confounders and parathyroid hormones,
      serum 25(OH)D levels were associated with a significantly decreased risk of PAD
      (OR for one SD increase, 0.98; 95% CI, 0.95-1.0, P for trend=0.040). Compared
      with the first 25(OH)D quartile, the odds of PAD were 0.86 (95% CI, 0.62-1.21),
      0.67 (95% CI, 0.46-0.97), and 0.71 (95% CI, 0.49-1.04) for the second, third, and
      fourth quartiles, respectively. In this cross-sectional study, we found that low
      serum 25(OH)D levels were associated with an increased risk of PAD, independent
      of traditional cardiovascular risk factors and parathyroid hormone. Our findings
      suggest that low vitamin D levels may contribute to PAD in the Korean population.

PMID- 27689034
TI  - A Case of Acute Pyelonephritis in Bilateral Renal Malrotation.

PMID- 27689035
TI  - The meaning of anti-Mullerian hormone levels in patients at a high risk of poor
      ovarian response.
AB  - Measurements of ovarian reserve play an important role in predicting the clinical
      results of assisted reproductive technology (ART). The ideal markers of ovarian
      reserve for clinical applications should have high specificity in order to
      determine genuine poor responders. Basal follicle-stimulating hormone levels,
      antral follicle count, and serum anti-Mullerian hormone (AMH) levels have been
      suggested as ovarian reserve tests that may fulfill this requirement, with serum
      AMH levels being the most promising parameter. Serum AMH levels have been
      suggested to be a predictor of clinical pregnancy in ART for older women, who are
      at a high risk for decreased ovarian response. We reviewed the prognostic
      significance of ovarian reserve tests for patients undergoing ART treatment, with
      a particular focus on the significance of serum AMH levels in patients at a high
      risk of poor ovarian response. 

PMID- 27689036
TI  - Comparison of static culture, micro-vibration culture, and micro-vibration
      culture with co-culture in poor ovarian responders.
AB  - OBJECTIVE: This study was conducted to compare the effects of static culture,
      dynamic culture, and the combination of dynamic culture with specialized surfaces
      involving co-culture on human embryonic development. Embryos cultured using
      conventional static culture (SC) techniques served as a control group. We
      compared dynamic culture using micro-vibration culture (MVC) and micro-vibration
      with co-culture (MCoC), in which autologous cumulus cells were used as a
      specialized surface. METHODS: We conducted a chart review of patients who were
      treated between January 2011 and November 2014 in order to compare embryonic
      development rates and pregnancy rates among the groups. Zygotes were cultured in
      micro-droplets, and embryos were subsequently selected for transfer. Some surplus
      embryos were cryopreserved, and the others were cultured for blastocyst
      development. A micro-vibrator was set at the frequency of 42 Hz for duration of 5
      seconds per 60 minutes to facilitate embryo development. RESULTS: No significant
      differences among the groups were present in patient's characteristics. However,
      the clinical pregnancy rates were significantly higher in the MVC group and the
      MCoC group than in the SC group. No significant differences were found in the
      blastocyst development rate between the SC group and the MVC group, but the
      blastocyst development rate in the MCoC group was significantly higher than in
      the SC and MVC groups. CONCLUSION: The clinical pregnancy rate was significantly
      increased by the application of micro-vibration to the embryonic cultures of poor
      responders. The blastocyst development rate was significantly increased by the
      application of MCoC to surplus embryos.

PMID- 27689037
TI  - The effect of the site of laser zona opening on the complete hatching of mouse
      blastocysts and their cell numbers.
AB  - OBJECTIVE: We studied the effect of the site of laser zona opening on the
      complete hatching of mouse blastocysts and the cell numbers of the completely
      hatched blastocysts. METHODS: Mouse blastocysts were randomly allocated to the
      inner cell mass (ICM) group (zona opening performed at the site of the ICM,
      n=125), the trophectoderm (TE) group (zona opening performed opposite to the ICM,
      n=125) and the control group (no zona opening, n=125). RESULTS: The rate of
      complete hatching of the blastocysts was not significantly different in the ICM
      and the TE group (84.8% vs 80.8%, respectively; p=0.402), but was significantly
      lower in the control group (51.2%, p<0.001). The cell numbers in the completely
      hatched blastocysts were comparable in the control group, the ICM group, and the
      TE group (69+/-19.3, 74+/-15.7, and 71+/-16.8, respectively; p=0.680).
      CONCLUSION: These findings indicate that the site of laser zona opening did not
      influence the rate of complete hatching of mouse blastocysts or their cell
      numbers.

PMID- 27689038
TI  - Percentage of motile spermatozoa at 22 hours after swim-up procedure: An
      indicator for intracytoplasmic sperm injection?
AB  - OBJECTIVE: The decision to use in vitro fertilization (IVF), intracytoplasmic
      sperm injection (ICSI), or split insemination (IVF-ICSI) in the first cycle is
      based on the number of motile sperm. Hence, total fertilization failure (TFF)
      often occurs during IVF cycles, despite normozoospermia. To investigate whether
      the cumulative motile swim-up spermatozoa percentage at 22 hours post
      insemination (MSPPI) is an indicator for ICSI, we analyzed TFF, fertilization,
      blastocyst development, chemical pregnancy, clinical pregnancy, and live birth
      rates. METHODS: This prospective study was performed using data obtained from 260
      IVF cycles. At 22 hours after insemination, the remaining swim-up spermatozoa
      were observed and divided into six groups according to MSPPI (<10%, 10% to <30%,
      30% to <50%, 50% to <70%, 70% to <90%, and 90% to 100%). RESULTS: Regardless of
      the ejaculated motile sperm concentration (0.6-280*10(6)/mL motile spermatozoa),
      the incidence of TFF significantly increased when MSPPI was <10%, and the
      fertilization rate significantly decreased when MSPPI was <30%. We found that
      cumulative MSPPI correlated with the cumulative fertilization rate (Spearman
      correlation, 0.508, p<0.001). Regarding embryo development, we observed no
      significant differences in the rates of blastocyst development, chemical
      pregnancy, clinical pregnancy, or live birth among all groups. CONCLUSION: Our
      findings suggest that MSPPI is a viable indicator for split IVF-ICSI and ICSI.
      Taken together, by employing the MSPPI test in advance before IVF, ICSI, or split
      IVF-ICSI cycles, unnecessary split IVF-ICSI and ICSI may be avoided.

PMID- 27689039
TI  - Clinical outcomes of single versus double blastocyst transfer in fresh and
      vitrified-warmed cycles.
AB  - OBJECTIVE: Assisted reproductive technology has been associated with an increase
      in multiple pregnancies. The most effective strategy for reducing multiple
      pregnancies is single embryo transfer. Beginning in October 2015, the National
      Supporting Program for Infertility in South Korea has limited the number of
      embryos that can be transferred per in vitro fertilization (IVF) cycle depending
      on the patient's age. However, little is known regarding the effect of age and
      number of transferred embryos on the clinical outcomes of Korean patients. Thus,
      this study was performed to evaluate the effect of the number of transferred
      blastocysts on clinical outcomes. METHODS: This study was carried out in the
      Fertility Center of CHA Gangnam Medical Center from January 2013 to December
      2014. The clinical outcomes of 514 women who underwent the transfer of one or two
      blastocysts on day 5 after IVF and of 721 women who underwent the transfer of one
      or two vitrified-warmed blastocysts were analyzed retrospectively. RESULTS: For
      both fresh and vitrified-warmed cycles, the clinical pregnancy rate and live
      birth or ongoing pregnancy rate were not significantly different between patients
      who underwent elective single blastocyst transfer (eSBT) and patients who
      underwent double blastocyst transfer (DBT), regardless of age. However, the
      multiple pregnancy rate was significantly lower in the eSBT group than in the DBT
      group. CONCLUSION: The clinical outcomes of eSBT and DBT were equivalent, but
      eSBT had a lower risk of multiple pregnancy and is, therefore, the best option.

PMID- 27689040
TI  - Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo
      transfer cycles following gonadotropin-releasing hormone agonist treatment.
AB  - OBJECTIVE: To determine the preferred regimen for women with adenomyosis
      undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh
      embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH)
      agonist pretreatment and of frozen-thawed embryo transfer (FET) cycles following
      GnRH agonist treatment. METHODS: This retrospective study included 241 IVF cycles
      of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles
      without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist
      pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group
      C) were compared. Adenomyosis was identified by using transvaginal ultrasound at
      the initial workup and classified into focal and diffuse types. The IVF outcomes
      were also subanalyzed according to the adenomyotic region. RESULTS: GnRH agonist
      pretreatment increased the stimulation duration (11.5+/-2.1 days vs. 9.9+/-2.0
      days) and total dose of gonadotropin (3,421+/-1,141 IU vs. 2,588+/-1,192 IU),
      which resulted in a significantly higher number of retrieved oocytes (10.0+/-8.2
      vs. 7.9+/-6.8, p=0.013) in group B than in group A. Controlled ovarian
      stimulation for freezing resulted in a significantly higher number of retrieved
      oocytes (14.3+/-9.2 vs. 10.0+/-8.2, p=0.022) with a lower dose of gonadotropin
      (2,974+/-1,112 IU vs. 3,421+/-1,141 IU, p=0.037) in group C than in group B. The
      clinical pregnancy rate in group C (39.5%) tended to be higher than those in
      groups B (30.5%) and A (25.2%) but without a significant difference. CONCLUSION:
      FET following GnRH agonist pretreatment tended to increase the pregnancy rate in
      patients with adenomyosis. Further large-scale prospective studies are required
      to confirm this result.

PMID- 27689041
TI  - Psychological distress and fertility quality of life (FertiQoL) in infertile
      Korean women: The first validation study of Korean FertiQoL.
AB  - OBJECTIVE: To investigate psychological distress and fertility quality of life
      (FertiQoL) in infertile Korean women, and to investigate whether a correlation
      exists between psychological distress and FertiQoL. METHODS: Participants in this
      study were made up of 141 infertile women and 65 fertile women. We conducted a
      survey on psychological distress (using the Depression Anxiety Stress Scales
      [DASS]-42 questionnaire) and administered a FertiQoL questionnaire. The levels of
      stress hormones (adrenocorticotropic hormone [ACTH] and cortisol) in serum were
      assessed. RESULTS: The scores for depression (13.7+/-8.4), anxiety (10.7+/-6.4),
      and stress (18.0+/-8.3) among the infertile women were significantly higher than
      the scores for depression (9.4+/-7.5), anxiety (6.6+/-6.0), and stress (12.2+/
      8.3, p<0.001) among the fertile women. There was no difference in the scores for
      depression (13.5+/-8.2, 13.8+/-8.6), anxiety (10.0+/-6.2, 11.5+/-6.6) and stress
      (17.7+/-8.4, 18.4+/-8.1) between younger (<=34) and older (>=35) participants.
      The mind-body (r =-0.495) and emotional (r =-0.590) subscales showed a higher
      negative correlation with stress compared with other scales of psychological
      distress. At the same time, the social (r =-0.537) and relational (r =-0.385)
      subscales showed a higher negative correlation with depression. Levels of
      cortisol and ACTH in infertile women were 9.1 ug/mL and 11.9 pg/mL, respectively,
      which are within normal ranges. CONCLUSION: The levels of psychological distress
      and quality of life in infertile Korean women seem to require psychological
      intervention. This study provides a baseline measurement of psychological
      distress and FertiQoL in infertile women in Korea, which will be available for
      developing psychological interventions for infertile Korean women.

PMID- 27689042
TI  - Live birth in a woman with recurrent implantation failure and adenomyosis
      following transfer of refrozen-warmed embryos.
AB  - The aim was to report a healthy live birth using re-vitrified-warmed cleavage
      stage embryos derived from supernumerary warmed embryos after frozen embryo
      transfer (ET) in a patient with recurrent implantation failure (RIF). The case
      was a 39-year-old female with a history of polycystic ovarian syndrome and
      adenomyosis, along with RIF. After ovarian hyperstimulation, 33 cumulus-oocyte
      complexes were retrieved and fertilized with conventional in vitro fertilization
      and intracytoplasmic sperm injection. Because of the risk of ovarian
      hyperstimulation syndrome, 16 grade B and C embryos were vitrified. After 3 and 6
      months, 3 and 4 B-C warmed embryos were transferred to the uterus, respectively.
      However, implantation did not take place. Ten months later, four embryos were
      warmed, two grade B 8-cell embryos were transferred, and two embryos were re
      vitrified. One year later, the two re-vitrified cleavage-stage embryos were
      warmed, which resulted in a successful live birth. This finding showed that
      following first warming, it is feasible to refreeze supernumerary warmed embryos
      for subsequent ET in patients with a history of RIF. 

PMID- 27689043
TI  - Why Are Some Periods and Places So Astonishingly More Productive than Others?

PMID- 27689044
TI  - PRS Korea 2016 in Its 50th Anniversary.

PMID- 27689045
TI  - The Efficacy and Safety of Tetrachlorodecaoxide in Comparison with Super-oxidised
      Solution in Wound Healing.
AB  - BACKGROUND: Some of the relatively newer, more efficacious, and potent topical
      wound dressing solutions include tetrachlorodecaoxide and super-oxidised
      solution. This study compares the efficacy and safety of these two drugs.
      METHODS: This is a block-randomised, double blind, parallel-arm, post-marketing
      study. One hundred fifty patients with ulcers (75 blocks uniform for sex, ulcer
      aetiology, diabetes mellitus, and wound area score) were randomised into the two
      treatment arms. Patients were observed for eight weeks with weekly assessments.
      One hundred and twenty patients completed the study. Wound healing was
      objectively assessed by measurement of wound area, scoring of wound exudation and
      tissue type, and using the pressure ulcer scale of healing Tool (validated for
      multiple wound aetiologies). Subjective improvement in pain was noted using a
      visual analogue scale. Both groups were compared using Mann-Whitney U test on all
      indicators. RESULTS: Difference in change in wound tissue type in the two groups
      was significant (alpha=0.05) by intention-to-treat (ITT) and per-protocol (PP)
      analysis at the end of week two (ITT and PP, P<0.001) and week four (ITT,
      P=0.010; PP, P=0.009). P-values for other comparisons were not significant
      (P>0.05). No study-related adverse events were observed. CONCLUSIONS: Both drugs
      are efficacious. Tetrachlorodecaoxide yields healthy granulation tissue earlier.
      Both drugs appear to be safe for application.

PMID- 27689046
TI  - Informed Consent as a Litigation Strategy in the Field of Aesthetic Surgery: An
      Analysis Based on Court Precedents.
AB  - BACKGROUND: In an increasing number of lawsuits doctors lose, despite providing
      preoperative patient education, because of failure to prove informed consent. We
      analyzed judicial precedents associated with insufficient informed consent to
      identify judicial factors and trends related to aesthetic surgery medical
      litigation. METHODS: We collected data from civil trials between 1995 and 2015
      that were related to aesthetic surgery and resulted in findings of insufficient
      informed consent. Based on these data, we analyzed the lawsuits, including the
      distribution of surgeries, dissatisfactions, litigation expenses, and
      relationship to informed consent. RESULTS: Cases were found involving the
      following types of surgery: facial rejuvenation (38 cases), facial contouring
      surgery (27 cases), mammoplasty (16 cases), blepharoplasty (29 cases),
      rhinoplasty (21 cases), body-contouring surgery (15 cases), and breast
      reconstruction (2 cases). Common reasons for postoperative dissatisfaction were
      deformities (22%), scars (17%), asymmetry (14%), and infections (6%). Most of the
      malpractice lawsuits occurred in Seoul (population 10 million people; 54% of
      total plastic surgeons) and in primary-level local clinics (113 cases, 82.5%). In
      cases in which only invalid informed consent was recognized, the average amount
      of consolation money was KRW 9,107,143 (USD 8438). In cases in which both
      violation of non-malfeasance and invalid informed consent were recognized, the
      average amount of consolation money was KRW 12,741,857 (USD 11,806),
      corresponding to 38.6% of the amount of the judgment. CONCLUSIONS: Surgeons
      should pay special attention to obtaining informed consent, because it is a
      double-edged sword; it has clinical purposes for doctors and patients but may
      also be a litigation strategy for lawyers.

PMID- 27689047
TI  - The Measurement of the Sensory Recovery Period in Zygoma and Blow-Out Fractures
      with Neurometer Current Perception Threshold.
AB  - BACKGROUND: Facial hypoesthesia is one of the most troublesome complaints in the
      management of facial bone fractures. However, there is a lack of literature on
      facial sensory recovery after facial trauma. The purpose of this study was to
      evaluate the facial sensory recovery period for facial bone fractures using
      Neurometer. METHODS: Sixty-three patients who underwent open reduction of
      zygomatic and blowout fractures between December 2013 and July 2015 were included
      in the study. The facial sensory status of the patients was repeatedly examined
      preoperatively and postoperatively by Neurometer current perception threshold
      (CPT) until the results were normalized. RESULTS: Among the 63 subjects, 30
      patients had normal Neurometer results preoperatively and postoperatively.
      According to fracture types, 17 patients with blowout fracture had a median
      recovery period of 0.25 months. Twelve patients with zygomatic fracture had a
      median recovery period of 1.00 month. Four patients with both fracture types had
      a median recovery period of 0.625 months. The median recovery period of all 33
      patients was 0.25 months. There was no statistically significant difference in
      the sensory recovery period between types and subgroups of zygomatic and blowout
      fractures. In addition, there was no statistically significant difference in the
      sensory recovery period according to Neurometer results and the patients' own
      subjective reports. CONCLUSIONS: Neurometer CPT is effective for evaluating and
      comparing preoperative and postoperative facial sensory status and evaluating the
      sensory recovery period in facial bone fracture patients.

PMID- 27689048
TI  - Feasibility of the Use of RapiGraft and Skin Grafting in Reconstructive Surgery.
AB  - BACKGROUND: Skin grafting is a relatively simple and thus widely used procedure.
      However, the elastic and structural quality of grafted skin is poor. Recently,
      various dermal substitutes have been developed to overcome this disadvantage of
      split-thickness skin grafts. The present study aims to determine the feasibility
      of RapiGraft as a new dermal substitute. METHODS: This prospective study included
      20 patients with partial- or full-thickness skin defects; the patients were
      enrolled between January 2013 and March 2014. After skin defect debridement, the
      wound was divided into two parts by an imaginary line. Split-thickness skin
      grafting alone was performed on one side (group A), and RapiGraft and split
      thickness skin grafting were used on the other side (group B). All patients were
      evaluated using photographs and self-questionnaires. The Manchester scar scale
      (MSS), a chromameter, and a durometer were used for the scar evaluation. The
      average follow-up period was 6 months. RESULTS: The skin graft take rates were
      93% in group A and 89% in group B, a non-significant difference (P=0.082).
      Statistically, group B had significantly lower MSS, vascularity, and pigmentation
      results than group A (P<0.05 for all). However, the groups did not differ
      significantly in pliability (P=0.155). CONCLUSIONS: The present study indicates
      that a simultaneous application of RapiGraft and a split-thickness skin graft is
      safe and yields improved results. Therefore, we conclude that the use of
      RapiGraft along with skin grafting will be beneficial for patients requiring
      reconstructive surgery.

PMID- 27689049
TI  - Acellular Dermal Matrix as a Core Strut for Projection in Nipple Reconstruction:
      Approaches for Three Different Methods of Breast Reconstruction.
AB  - BACKGROUND: The objective of this paper was to describe a novel technique for
      improving the maintenance of nipple projection in primary nipple reconstruction
      by using acellular dermal matrix as a strut in one of three different
      configurations, according to the method of prior breast reconstruction. The
      struts were designed to best fill the different types of dead spaces in nipple
      reconstruction depending on the breast reconstruction method. METHODS: A total of
      50 primary nipple reconstructions were performed between May 2012 and May 2015.
      The prior breast reconstruction methods were latissimus dorsi (LD) flap (28
      cases), transverse rectus abdominis myocutaneous (TRAM) flap (10 cases), or
      tissue expander/implant (12 cases). The nipple reconstruction technique involved
      the use of local flaps, including the C-V flap or star flap. A 1*2-cm acellular
      dermal matrix was placed into the core with O-, I-, and L-shaped struts for prior
      LD, TRAM, and expander/implant methods, respectively. The projection of the
      reconstructed nipple was measured at the time of surgery and at 3, 6, and 9
      months postoperatively. RESULTS: The nine-month average maintenance of nipple
      projection was 73.0%+/-9.67% for the LD flap group using an O-strut, 72.0%+/
      11.53% for the TRAM flap group using an I-strut, and 69.0%+/-10.82% for the
      tissue expander/implant group using an L-strut. There were no cases of infection,
      wound dehiscence, or flap necrosis. CONCLUSIONS: The application of an acellular
      dermal matrix with a different kind of strut for each of 3 breast reconstruction
      methods is an effective addition to current techniques for improving the
      maintenance of long-term projection in primary nipple reconstruction.

PMID- 27689051
TI  - Clinical Experiences with the Scapular Fascial Free Flap.
AB  - BACKGROUND: The goal of reconstruction is to provide coverage of exposed vital
      structures with well-vascularized tissue for optimal restoration of form and
      function. Here, we present our clinical experience with the use of the scapular
      fascial free flap to correct facial asymmetry and to reconstruct soft tissue
      defects of the extremities. METHODS: We used a scapular fascial free flap in 12
      cases for soft tissue coverage of the extremities or facial soft tissue
      augmentation. RESULTS: The flaps ranged in size from 3*12 to 13*23 cm. No cases
      of total loss of the flap occurred. Partial loss of the flap occurred in 1
      patient, who was treated with a turnover flap using the adjacent scapular fascial
      flap and a skin graft. Partial loss of the skin graft occurred in 4 patients due
      to infection or hematoma beneath the graft, and these patients underwent another
      skin graft. Four cases of seroma at the donor site occurred, and these cases were
      treated with conservative management or capsulectomy and quilting sutures.
      CONCLUSIONS: The scapular fascial free flap has many advantages, including a
      durable surface for restoration of form and contours, a large size with a
      constant pedicle, adequate surface for tendon gliding, and minimal donor-site
      scarring. We conclude that despite the occurrence of a small number of
      complications, the scapular fascial free flap should be considered to be a viable
      option for soft tissue coverage of the extremities and facial soft tissue
      augmentation.

PMID- 27689050
TI  - Three-Dimensional Surface Imaging is an Effective Tool for Measuring Breast
      Volume: A Validation Study.
AB  - BACKGROUND: Accurate breast volume assessment is a prerequisite to preoperative
      planning, as well as intraoperative decision making in breast reconstruction
      surgery. The use of three-dimensional surface imaging (3D scanning) to assess
      breast volume has many advantages. However, before employing 3D scanning in the
      field, the tool's validity should be demonstrated. The purpose of this study was
      to confirm the validity of 3D-scanning technology for evaluating breast volume.
      METHODS: We reviewed the charts of 25 patients who underwent breast
      reconstruction surgery immediately after total mastectomy. Breast volumes using
      the Axis Three 3D scanner, water-displacement technique, and magnetic resonance
      imaging (MRI) were obtained bilaterally in the preoperative period. During the
      operation, the tissue removed during total mastectomy was weighed and the
      specimen volume was calculated from the weight. Then, we compared the volume
      obtained from 3D scanning with those obtained using the water-displacement
      technique, MRI, and the calculated volume of the tissue removed. RESULTS: The
      intraclass correlation coefficient (ICC) of breast volumes obtained from 3D
      scanning, as compared to the volumes obtained using the water-displacement
      technique and specimen weight, demonstrated excellent reliability. The ICC of
      breast volumes obtained using 3D scanning, as compared to those obtained by MRI,
      demonstrated substantial reliability. Passing-Bablok regression showed agreement
      between 3D scanning and the water-displacement technique, and showed a linear
      association of 3D scanning with MRI and specimen volume, respectively.
      CONCLUSIONS: When compared with the classical water-displacement technique and
      MRI-based volumetry, 3D scanning showed significant reliability and a linear
      association with the other two methods.

PMID- 27689052
TI  - Reconstruction of Large Defects in the Perineal Area Using Multiple Perforator
      Flaps.
AB  - BACKGROUND: Perineal defects are commonly encountered during the treatment of
      conditions such as malignancy, infectious disease, and trauma. Covering large
      defects in the perineal area is challenging due to its complicated anatomy and
      the need for functional preservation. METHODS: Fourteen patients who underwent
      reconstructive surgery with multiple perforator flaps for defects >100 cm(2) in
      the perineal area were included in this retrospective cohort study.
      Characteristics of the perforator flap operation and postoperative outcomes were
      reviewed. RESULTS: Reconstruction was performed using 2 perforator flaps for 13
      patients and 3 perforator flaps for 1 patient. Internal pudendal artery
      perforator flaps were mainly used for covering the defects. The average defect
      size was 176.3+/-61.8 cm(2) and the average size of each flap was 95.7+/-31.9
      cm(2). Six patients had minor complications, such as wound dehiscence and partial
      necrosis of the flap margin, which were corrected with simple revision
      procedures. CONCLUSIONS: Multiple perforator flaps can be used to achieve
      successful reconstructions of large perineal defects that are difficult to
      reconstruct with other coverage methods.

PMID- 27689053
TI  - Rhinoplasty Education Using a Standardized Patient Encounter.
AB  - BACKGROUND: Comprehensive aesthetic surgery training continues to be a challenge
      for residency programs. Our residency program developed a rhinoplasty-based
      objective structured clinical examination (OSCE) based upon validated methods as
      part of the residency education curriculum. We report our experience with the
      rhinoplasty-based OSCE and offer guidance to its incorporation within residency
      programs. METHODS: The encounter involved resident evaluation and operative
      planning for a standardized patient desiring a rhinoplasty procedure. Validated
      OSCE methods currently used at our medical school were implemented. Residents
      were evaluated on appropriate history taking, physical examination, and
      explanation to the patient of treatment options. Examination results were
      evaluated using analysis of variance (statistical significance P<0.05). RESULTS:
      Twelve residents completed the rhinoplasty OSCE. Medical knowledge assessment
      showed increasing performance with clinical year, 50% versus 84% for postgraduate
      year 3 and 6, respectively (P<0.005). Systems-based practice scores showed that
      all residents incorrectly submitted forms for billing and operative scheduling.
      All residents confirmed that the OSCE realistically represents an actual patient
      encounter. All faculty confirmed the utility of evaluating resident performance
      during the OSCE as a useful assessment tool for determining the Next
      Accreditation System Milestone level. CONCLUSIONS: Aesthetic surgery training for
      residents will require innovative methods for education. Our examination showed a
      program-educational weakness in billing/coding, an area that will be improved
      upon by topic-specific lectures. A thoroughly developed OSCE can provide a
      realistic educational opportunity to improve residents' performance on the
      nonoperative aspects of rhinoplasty and should be considered as an adjunct to
      resident education.

PMID- 27689054
TI  - Immediate Bilateral Breast Reconstruction with Unilateral Deep Superior
      Epigastric Artery and Superficial Circumflex Iliac Artery Flaps.
AB  - Autologous breast reconstruction utilizing a perforator flap is an increasingly
      popular method for reducing donor site morbidity and implant-related
      complications. However, aberrant anatomy not readily visible on computed
      tomography angiography is a rare albeit real risk when undergoing perforator flap
      reconstruction. We present an operative case of a patient who successfully
      underwent a bilateral breast reconstruction sourced from a unilateral abdominal
      flap divided into deep superior epigastric artery and superficial circumflex
      iliac artery flap segments. 

PMID- 27689056
TI  - A Simple, Reliable, and Inexpensive Intraoperative External Expansion System for
      Enhanced Autologous Structural Fat Grafting.
AB  - External volume expansion of the recipient site by suction has been proposed as a
      way of improving fat graft survival. The objective of this study was to present
      an innovative and simple intraoperative external expansion system to enhance
      small-volume autologous fat grafting (40-80 mL) and to discuss its background and
      its mechanism of action. In this system, expansion is performed using a complete
      vacuum delivery system known as the Kiwi VAC-6000M with a PalmPump (Clinical
      Innovations). The recipient site is rapidly expanded intraoperatively 10 times
      for 30 seconds each with a negative pressure of up to 550 mm Hg before autologous
      fat injection. During this repetitive stimulation, the tissues become grossly
      expanded, developing macroscopic swelling that regresses slowly over the course
      of hours following the cessation of the stimulus. The system sets various
      mechanisms in motion, including scar release, mechanical stimulation, edema,
      ischemia, and inflammation, which provide an environment conducive for cell
      proliferation and angiogenesis. In order to maintain the graft construct in its
      expansive state, all patients are encouraged postoperatively to use the Kiwi
      three times daily for one minute per session over the course of three days. The
      handling of this system is simple for both the patients and the surgeon.
      Satisfactory clinical outcomes have been achieved without significant
      complications. 

PMID- 27689055
TI  - Three-Directional Reconstruction of a Massive Perineal Defect after Wide Local
      Excision of Extramammary Paget's Disease.
AB  - Extramammary Paget's disease (EMPD) is a rare, slow-growing intraepithelial
      malignancy that mainly involves the genital region, including the vulva, penis,
      scrotum, perianal, and periurethral areas. Although several treatment options
      exist, wide local excision with a safe margin is considered the treatment of
      choice. After resection of the lesion, it is often challenging to reconstruct the
      defect because defects in the perineal region require adequate volume for
      protection and are susceptible to infections, which is a particularly significant
      risk for large defects. We report a case of perivulvar EMPD that was
      reconstructed with three-directional local flaps after wide excision of the
      tumor. We covered the defect sequentially using the following 3 flaps: a gracilis
      myocutaneous flap from the left thigh, a bipedicled V-Y advancement flap from the
      lower abdomen, and an internal pudendal artery perforator-based island flap from
      the right buttock. To the best of our knowledge, this report is the first to
      describe a three-directional approach to extensive perivulvar reconstruction. 

PMID- 27689057
TI  - A Novel Nipple Reconstruction Technique for Maintaining Nipple Projection: The
      Boomerang Flap.
AB  - Nipple-areolar complex (NAC) reconstruction is the final step in the long journey
      of breast reconstruction for mastectomy patients. Successful NAC reconstruction
      depends on the use of appropriate surgical techniques that are simple and
      reliable. To date, numerous techniques have been used for nipple reconstruction,
      including contralateral nipple sharing and various local flaps. Recently, it has
      been common to utilize local flaps. However, the most common nipple
      reconstruction problem encountered with local flaps is the loss of nipple
      projection; there can be approximately 50% projection loss in reconstructed
      nipples over long-term follow-up. Several factors might contribute to nipple
      projection loss, and we tried to overcome these factors by performing nipple
      reconstructions using a boomerang flap technique, which is a modified C-V flap
      that utilizes the previous mastectomy scar to maintain long-term nipple
      projection. 

PMID- 27689058
TI  - Kabuki Syndrome with Cleft Palate.

PMID- 27689059
TI  - Hydrocele of the Canal of Nuck in a Female Adult.

PMID- 27689060
TI  - Acute Febrile Neutrophilic Dermatosis after Deep Inferior Epigastric Perforator
      Flap Breast Reconstruction.

PMID- 27689061
TI  - Calcifications on the Entire Legs of a Systemic Lupus Erythematosus Patient.

PMID- 27689062
TI  - Incidental Finding of Mucosa-Associated Lymphoid Tissue Lymphoma during Lower
      Blepharoplasty.

PMID- 27689063
TI  - Correlation between clinicians-assigned weights to findings and their diagnostic
      odd ratio; case of congestive heart failure.
AB  - BACKGROUND: Incorrect estimation of pretest probability and misinterpretation of
      test results can change post-test probability in medical decision making. The aim
      of this study was to evaluate how physicians assess weight of findings of
      congestive heart failure (CHF) and how much their estimation is correlated with
      findings' Diagnostic Odd Ratio (DOR). METHODS: The participants were asked to
      answer a questionnaire based on a scenario of a patient having dyspnea. Eighteen
      findings in 3 categories including: history, examination and radiographic
      findings were inserted along a column and a row as a matrix. The respondents had
      to compare each finding in the column with all other findings in the row and
      insert a mark in boxes below the findings of the row that had greater weight
      compared to the finding in the column. The weight of each finding was considered
      as total number of "marked boxes" in front of that finding. DOR of findings was
      calculated using their positive and negative likelihood ratios (LRs) based on
      current best evidence. Findings ranked in the order of their DOR and were
      compared with the ranking in the order of participants-assigned weights. We
      examined correlation between average weights assigned by physicians and DOR of
      findings. In subgroup analysis correlations between average weights assigned by
      physicians and DOR of history, examination and radiographic findings were
      examined. RESULTS: Seventy five physicians completed the questionnaire.
      Correlation between ranking in the order of findings' DOR and ranking in the
      order of clinicians-assigned weights was significant (p-value = 0.005 r = 0.64).
      In contrast correlations between participants-assigned weights and DOR of
      history, examination and radiographic findings were positive but non- significant
      (r = 0.181, p-value = 0.7, r = 0.343, p-value = 0.506 and r = 0.219, p-value =
      0.723 respectively). CONCLUSION: Our result show that although correlation
      between clinicians-assigned weights and DOR of entire findings was significant,
      correlations between clinicians-assigned weights to the different categories of
      findings and their DOR were not significant. Reevaluating probabilistic reasoning
      by emphasis on using LRs can make pretest probability estimating and
      interpretation of test results more objective and would ultimate in more precise
      and homogenous post-test probabilities.

PMID- 27689064
TI  - Oxidative stress in prostate cancer patients: A systematic review of case control
      studies.
AB  - BACKGROUND: Prostate cancer (PCa) is the most common cancer in men in Western
      countries. In-vitro and in-vivo studies suggest that oxidative stress (OS) and
      antioxidants play a key role in the pathogenesis of chronic diseases including
      PCa, which is promoted by the production of reactive oxygen species and impaired
      antioxidant defense mechanisms. This study evaluates the association between OS
      and men with PCa. METHODS: A literature search was carried out on Medline,
      PubMed, and ScienceDirect databases, as well as manual searches from inception up
      to August 2015 using the keywords "Oxidative stress" or "Reactive oxygen species"
      or "Lipid peroxidation" AND "Prostate cancer." All studies including data on the
      measurement of OS biomarkers in PCa were included. RESULTS: Twenty-three case
      control studies were retrieved with sample sizes ranging from 15 to 3,613 (6,439
      participants in total). Markers of OS were significantly higher in patients with
      PCa compared with control groups in 21 studies. Two self-controlled case studies
      comparing OS between PCa cells and non-PCa cells in tissue biopsies found OS to
      be statistically higher in PCa cancer cells. Results on markers of antioxidant
      capacity (superoxide dismutase, catalase, glutathione, glutathione reductase,
      glutathione peroxidase, uric acid, lutein, lycopene, beta carotein, vitamin A,
      vitamin C, vitamin E, and total antioxidants) were not completely consistent in
      their association with PCa. CONCLUSIONS: Upregulated OS profiles and impairment
      of antioxidant defense systems may play a role in men with PCa. To confirm these
      findings, robust clinical trials utilizing a personalized approach which monitors
      both OS and antioxidant markers during therapy are warranted.

PMID- 27689065
TI  - Asia prostate cancer study (A-CaP Study) launch symposium.
AB  - The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been
      developed over the course of 2 years. The A-CaP Study is scheduled to begin in
      2016, when each participating country or region will begin registration of newly
      diagnosed prostate cancer patients and conduct prognosis investigations. From the
      data gathered, common research themes will be identified, such as comparisons
      among Asian countries of background factors in newly diagnosed prostate cancer
      patients. This is the first Asia-wide study of prostate cancer and has developed
      from single country research efforts in this field, including in Japan and Korea.
      The inaugural Board Meeting of A-CaP was held on December 11, 2015 at the
      Research Center for Advanced Science and Technology, The University of Tokyo,
      attended by representatives of all participating countries and regions, who
      signed a memorandum of understanding concerning registration for A-CaP. Following
      the Board Meeting an A-CaP Launch Symposium was held. The symposium was attended
      by representatives of countries and regions participating in A-CaP, who gave
      presentations. Presentations and a keynote address were also delivered by
      representatives of the University of California San Francisco, USA, and the Peter
      MacCallum Cancer Centre, Australia, who provided insight and experience on
      similar databases compiled in their respective countries. 

PMID- 27689067
TI  - Cytoreductive surgery for men with metastatic prostate cancer.
AB  - BACKGROUND: Cytoreductive surgery for metastatic prostate cancer is an emerging
      area of interest with a potential upside that includes local control, delayed
      initiation of hormone therapy, and possibly improved cancer specific survival. In
      order for radical prostatectomy to be an effective treatment option for men in
      this group, the benefits must outweigh the surgical morbidity. The aim of this
      study was to present a case series and assess the literature feasibility of
      cytoreductive surgery for men with metastatic prostate cancer. METHODS: A
      retrospective review of clinical notes was performed to identify men with
      metastatic prostate cancer who underwent cytoreductive surgery between 2012 and
      2014 for a group of urologists at a single institution in Melbourne. Each patient
      was evaluated with regard to preoperative prostate-specific antigen, grade,
      stage, adjuvant therapy, and surgical outcomes. RESULTS: Six cases were
      identified. This included 1 pelvic exenteration and 5 robot-assisted radical
      prostatectomies. The men who underwent RARP had uncomplicated recoveries,
      regained continence within 3 months and remained pad-free at follow up. All
      patients proceeded to additional treatment of sites of metastatic disease with a
      variable PSA response, however, 3 of 6 men required recommencement of ADT for
      biochemical progression at follow up. CONCLUSIONS: This data supports recent
      findings demonstrating that radical prostatectomy for metastatic prostate cancer
      is feasible. Further studies are needed to explore the role of cytoreductive
      surgery with regards to the potential oncological benefit.

PMID- 27689066
TI  - Prostate-based biofluids for the detection of prostate cancer: A comparative
      study of the diagnostic performance of cell-sourced RNA biomarkers.
AB  - BACKGROUND: Prostate cancer (PCa) diagnosis requires improvement with the aid of
      more accurate biomarkers. Postejaculate urethral washings (PEUW) could be a
      physiological equivalent to urine obtained following rectal prostatic massage,
      the current basis for the prostate cancer antigen 3 (PCA3) test. The aim of this
      study was to investigate if PEUW contained prostate-based material, evidenced by
      the presence of prostate specific antigen (PSA), and to evaluate the diagnostic
      performance of PEUW-based biomarkers. METHODS: Male patients referred for
      elevated serum PSA or abnormal digital rectal examination provided ejaculate and
      PEUW samples. PSA, PCA3, and beta2-microglobulin (beta2M) were quantified in
      ejaculate and PEUW and compared with absolute and clinically significant
      (according to D'Amico criteria) PCa presence, as determined by biopsies.
      Diagnostic performance was determined and compared with serum PSA using receiver
      operating characteristic analysis. RESULTS: From 83 patients who provided PEUW
      samples, paired analysis with ejaculate samples was possible for 38 patients,
      while analysis in an unpaired, extended cohort was possible for 62 patients. PSA
      and PCA3 were detected in PEUW, normalized to beta2M, and PCA3:PSA was
      calculated. In predicting absolute PCa status, PCA3:beta2M in ejaculate [area
      under the curve (AUC) 0.717] and PEUW (AUC 0.569) were insignificantly better
      than PCA3:PSA (AUC 0.668 and 0.431, respectively) and comparable with serum PSA
      (AUC 0.617) with similar trends observed for the extended cohort. When
      considering clinically significant PCa presence, serum PSA in the comparison (AUC
      0.640) and extended cohorts (AUC 0.665) was comparable with PCA3: beta2M (AUC
      0.667) and PCA3:PSA (AUC 0.605) in ejaculate, with lower estimates for PEUW in
      the comparison (PCA3: beta2M AUC 0.496; PCA3:PSA AUC 0.342) and extended (PCA3:
      beta2M AUC 0.497; PCA3:PSA AUC 0.469) cohorts. The statistical analysis was
      limited by sample size. CONCLUSION: PEUW contains prostatic material, but has
      limited diagnostic accuracy when considering cell-derived DNA analysis. PCA3
      based markers in ejaculate are comparable to serum PSA and digital rectal
      examination-urine markers.

PMID- 27689068
TI  - Incidental prostate cancer diagnosed at radical cystoprostatectomy for bladder
      cancer: disease-specific outcomes and survival.
AB  - BACKGROUND: The current standard of care for men with muscle-invasive bladder
      cancer is radical cystoprostatectomy (RCP). One-third of RCP specimens
      demonstrate incidental prostate cancer, primarily reported in small series with
      limited follow-up. The aim of this study is to report mature outcomes, including
      patterns of failure and disease-specific recurrence rates, and survival, for a
      large cohort of men with incidental prostate cancer at RCP performed at a
      tertiary referral center. METHODS: This retrospective study describes cancer
      control and survival rates for men who underwent RCP for bladder cancer and were
      found incidentally to have prostate cancer. Analysis of patient-, tumor-, and
      treatment-specific factors were analyzed for association with disease control and
      survival endpoints. RESULTS: Between 2002 and 2010, 94 patients with incidental
      discovery of prostate cancer postRCP were identified for inclusion in this study.
      Forty-five patients (45%) underwent RCP for recurrent (rather than initial
      presentation of) bladder carcinoma. At a median follow-up of 40.3 months (71.2
      months for survivors; range, 8.9-155.5 months), 42 patients were alive without
      recurrence and 52 patients had died (25 associated with disease). The estimated 5
      year bladder cancer disease-free, urinary tract malignancy disease-free, and
      prostate specific antigen (PSA) relapse-free survivals were 76% [95% confidence
      interval (CI), 65-84%], 64% (52-74%), and 97% (79-100%), respectively. The
      estimated 5-year urinary tract malignancy-specific and overall survivals were 61%
      (49-71%) and 52% (41-62%), respectively. Univariate analysis demonstrated
      associations between pathologic T/N-stage and nodal ratio with bladder cancer
      disease-free, urinary tract malignancy disease-specific, and overall survivals,
      with patient age at diagnosis as an additional adverse factor associated with
      overall survival. Multivariate analysis confirmed pN-stage and age as
      independently associated with worse survival. CONCLUSION: For men undergoing RCP
      for bladder cancer, the present study suggests that incidentally discovered
      prostate cancers, irrespective of pathologic stage, Gleason score, or clinical
      significance, do not impact 5-year disease control or survival outcomes.

PMID- 27689069
TI  - Optimizing prophylactic antibiotic regimen in patients admitted for transrectal
      ultrasound-guided prostate biopsies: A prospective randomized study.
AB  - BACKGROUND: Transrectal ultrasound-guided prostate biopsies (TRUSBx), in spite of
      being one of the most frequently performed urological office procedures, are
      associated with a spectrum of complications, most significantly including
      infection. The aim of the study is to evaluate the prevalence of fluoroquinolone
      resistant bacteria in rectal swabs from our local population prior to TRUSBx and
      to identify risk factors among a patient population harboring fluoroquinolone
      resistant organisms. METHODS: We prospectively included 541 men who were
      submitted for TRUSBx in our center from March 2011 to June 2015. The indications
      for TRUSBx were an elevated prostate-specific antigen level and/or abnormal
      digital rectal exam. All patients were randomly divided into two groups: Group 1
      (n = 279 cases) who received standard empirical prophylactic antibiotics and
      Group 2 who received targeted prophylaxis based on a rectal swab culture and
      susceptibility result. Differences in risk factors between quinolone-resistant
      and nonresistant patients were compared. Univariate and multivariate analyses
      were performed to identify independent potential risk factors associated with
      fluoroquinolone-resistant rectal flora. RESULTS: Sixteen out of 271 men developed
      infectious complications after TRUSBx in the group receiving standard empirical
      prophylaxis (5.7%). No men in the group who received targeted prophylactic
      antibiotic guided by rectal swab developed infectious complications. Among the
      262 patients who underwent prebiopsy rectal swab cultures, 76 men (29%) displayed
      fluoroquinolone-resistant rectal flora (29%). In the multivariate analysis, a
      history of antibiotic exposure before prostate biopsy was the only independent
      factor associated with an increased risk of fluoroquinolone resistance.
      CONCLUSION: Determining the prevalence of fluoroquinolone resistance in rectal
      flora has important implications in the selection of targeted prophylactic
      antibiotic regimens. Antimicrobial profiles guided by rectal swabs may prove
      useful to optimize prophylaxis prior to TRUSBx; this strategy is effective at
      reducing the rates of infectious complications, including sepsis, especially in
      men at higher risk of infectious complications.

PMID- 27689070
TI  - Incidence and mortality of prostate cancer and their relationship with the Human
      Development Index worldwide.
AB  - BACKGROUND: The aim of this study was to evaluate the incidence and mortality of
      prostate cancer and their relationship with the Human Development Index (HDI) and
      its components in Asia in 2012. METHODS: This study was an ecological study
      conducted based on the GLOBOCAN project of the World Health Organization. The
      correlation between standardized incidence rate (SIR) and standardized mortality
      rate (SMR) of prostate cancer with HDI and its components was assessed using SPSS
      Inc Version 18.0 (Chicago). RESULTS: There were 1,094,916 incident cases of
      prostate cancer and 307,481 deaths recorded in 2012 worldwide. SIR and SMR due to
      HDI were 72 and 9.7 in very high human development regions, 37.5 and 12.9 in high
      human development regions, 7 and 3.7 in medium human development regions, and
      14.9 and 12.1 in low human development regions per 100,000 people, respectively.
      A positive correlation of 0.475 was seen between SIR of prostate cancer and HDI
      (P <= 0.001). Also, a negative correlation of 0.160 was seen between SMR of
      prostate cancer and HDI (P = 0.032). CONCLUSION: The incidence of prostate cancer
      is high in countries with higher development. A positive correlation was observed
      between the SIR of prostate cancer and the HDI and its components, such as life
      expectancy at birth, mean years of schooling, and the gross national income per
      capita. In addition, there was a negative correlation between SMR and HDI.

PMID- 27689071
TI  - Embracing Integrative Multiomics Approaches.
AB  - As "-omics" data technology advances and becomes more readily accessible to
      address complex biological questions, increasing amount of cross "-omics" dataset
      is inspiring the use and development of integrative bioinformatics analysis. In
      the current review, we discuss multiple options for integrating data across "
      omes" for a range of study designs. We discuss established methods for such
      analysis and point the reader to in-depth discussions for the various topics.
      Additionally, we discuss challenges and new directions in the area. 

PMID- 27689072
TI  - The Role of Pancreatic Stone Protein in Diagnosis of Early Onset Neonatal Sepsis.
AB  - Introduction. Early diagnosis and treatment of neonatal sepsis may help decrease
      neonatal mortality. Aim of the Study. To evaluate the role of pancreatic stone
      protein as a marker for early onset neonatal sepsis. Methods. A hospital-based
      prospective study was conducted on 104 (52 uninfected and 52 infected neonates)
      admitted to the Neonatal Intensive Care Unit (NICU) of Zagazig University
      hospitals during the period from April 2014 to April 2015. All newborns were
      subjected to full history taking, careful neonatal assessment, blood, C-reactive
      protein (CRP), and serum pancreatic stone protein. Results. Serum PSP levels were
      significantly higher in the infected group than in the uninfected group. At a
      cutoff level of PSP 12.96 ng/mL, the sensitivity was 96.2%, the specificity was
      88.5%, positive predictive value was 95.8%, negative predictive value was 89.3%,
      and area under the curve was 0.87. A significant positive correlation between CRP
      and PSP was found in infected group. Conclusion. The high negative predictive
      value of PSP (89.3%) indicates that the serum PSP level is a good marker for
      diagnosis of early onset neonatal sepsis and can be used to limit hospital stay
      and antibiotic use in neonates treated for suspected sepsis.

PMID- 27689073
TI  - Differences in Dry Eye Questionnaire Symptoms in Two Different Modalities of
      Contact Lens Wear: Silicone-Hydrogel in Daily Wear Basis and Overnight
      Orthokeratology.
AB  - Purpose. To compare the ocular surface symptoms and signs in an adult population
      of silicone-hydrogel (Si-Hy) contact lens (CL) wearers with another modality of
      CL wear, overnight orthokeratology (OK). Materials and Methods. This was a
      prospective and comparative study in which 31 myopic subjects were fitted with
      the same Si-Hy CL and 23 underwent OK treatment for 3 months. Dry eye
      questionnaire (DEQ) was filled in at the beginning of the study and then after 15
      days, 1 month, and 3 months using each CL modality. The tear quality was
      evaluated with noninvasive tear break-up time. Tear production was measured with
      Schirmer test. Tear samples were collected with Schirmer strips being frozen to
      analyze the dinucleotide diadenosine tetraphosphate (Ap4A) concentration with
      High-Performance Liquid Chromatography (HPLC). Results. After refitting with
      ortho-k, a reduction in discomfort and dryness symptoms at the end of the day (p
      < 0.05, chi2) was observed. No significant changes were observed in Ap4A
      concentration in any group. Bulbar redness, limbal redness, and conjunctival
      staining increased significantly in the Si-Hy group (p < 0.05, Kruskal-Wallis
      test). Conclusion. Discomfort and dryness symptoms at the end of the day are
      lower in the OK CL group than in the Si-Hy CL group.

PMID- 27689074
TI  - Molecular Characterization of LRB7 Gene and a Water Channel Protein TIP2 in
      Chorispora bungeana.
AB  - Background. Water channel proteins, also called aquaporins, are integral membrane
      proteins from major intrinsic protein (MIP) family and involved in several
      pathways including not only water transport but also cell signaling,
      reproduction, and photosynthesis. The full cDNA and protein sequences of
      aquaporin in Chorispora bungeana Fisch. & C.A. Mey (C. bungeana) are still
      unknown. Results. In this study, PCR and rapid amplification of cDNA ends
      approaches were used to clone the full cDNA of LRB7 (GenBank accession number:
      EU636988) of C. bungeana. Sequence analysis indicated that it was 1235 bp, which
      had two introns and encoded a protein of 250 amino acids. Structure analysis
      revealed that the protein had two conserved NPA motifs, one of which is MIP
      signature sequence (SGxHxNPAVT), six membrane helix regions, and additional
      membrane-embedded domains. Phylogenetic analysis suggested that the protein was
      from TIP2 subgroup. Surprisingly, semiquantitative RT-PCR experiment and western
      blot analysis showed that LRB7 and TIP2 were only detectable in roots, unlike
      Arabidopsis and Raphanus. Connecting with our previous studies, LRB7 was
      supported to associate with chilling-tolerance in C. bungeana. Conclusion. This
      is the first time to characterize the full sequences of LRB7 gene and water
      channel protein in C. bungeana. Our findings contribute to understanding the
      water transports in plants under low temperatures.

PMID- 27689075
TI  - Effects of Berberine on NLRP3 and IL-1beta Expressions in Monocytic THP-1 Cells
      with Monosodium Urate Crystals-Induced Inflammation.
AB  - Background. Urate crystals-induced inflammation is a critical factor during the
      initiation of gouty arthritis. Berberine is well known for its anti-inflammatory
      activity. However, the underlying effects of berberine on monosodium urate
      crystals-induced inflammation remain obscure. Objectives. This study is set to
      explore the protective effect and mechanism of berberine on monosodium urate
      crystals-induced inflammation in human monocytic THP-1 cells. Methods. The mRNA
      levels of NLRP3 and IL-1beta were measured by Real-Time PCR, and the protein
      levels of NLRP3 and IL-1beta were determined by ELISA, Western blot, and
      immunofluorescence. Results. The NLRP3 and IL-1beta expressions were
      significantly increased in model group compared to that in normal group (P <
      0.05). Meanwhile, there was significant reduction in the expressions of NLRP3 and
      IL-1beta mRNA in groups 6.25 MUM berberine and 25 MUM berberine when compared
      with model group (P < 0.05). Conclusions. Therefore, berberine alleviates
      monosodium urate crystals-induced inflammation by downregulating NLRP3 and IL
      1beta expressions. The regulatory effects of berberine may be related to the
      inactivation of NLRP3 inflammasome.

PMID- 27689076
TI  - An Improved Total Variation Minimization Method Using Prior Images and Split
      Bregman Method in CT Reconstruction.
AB  - Compressive Sensing (CS) theory has great potential for reconstructing Computed
      Tomography (CT) images from sparse-views projection data and Total Variation- (TV
      ) based CT reconstruction method is very popular. However, it does not directly
      incorporate prior images into the reconstruction. To improve the quality of
      reconstructed images, this paper proposed an improved TV minimization method
      using prior images and Split-Bregman method in CT reconstruction, which uses
      prior images to obtain valuable previous information and promote the subsequent
      imaging process. The images obtained asynchronously were registered via Locally
      Linear Embedding (LLE). To validate the method, two studies were performed.
      Numerical simulation using an abdomen phantom has been used to demonstrate that
      the proposed method enables accurate reconstruction of image objects under sparse
      projection data. A real dataset was used to further validate the method.

PMID- 27689077
TI  - The Relationship between Neurocircuitry Dysfunctions and Attention Deficit
      Hyperactivity Disorder: A Review.
AB  - The prefrontal cortex is the superlative structure of brain that needs the
      longest developmental and maturational duration that highlights the region of
      attention deficit hyperactivity disorder (ADHD) in neuroimaging studies.
      Prefrontal cortex functions generate enormously complex and its abundant feedback
      neurocircuitries with subcortical structures such as striatum and thalamus
      established through dual neural fibers. These microneurocircuitries are called
      corticostriatothalamocortical (CSTC) circuits. The CSTC circuits paly an
      essential role in flexible behaviors. The impaired circuits increase the risk of
      behavioral and psychological symptoms. ADHD is an especial developmental stage of
      paediatric disease. It has been reported that the CSTC circuits dysfunctions in
      ADHD are related to homologous symptoms. This study aimed to review the symptoms
      of ADHD and discuss the recent advances on the effects of the disease as well as
      the new progress of treatments with each circuit.

PMID- 27689080
TI  - Retracted: Leaf Rolling and Stem Fasciation in Grass Pea (Lathyrus sativus L.)
      Mutant Are Mediated through Glutathione-Dependent Cellular and Metabolic Changes
      and Associated with a Metabolic Diversion through Cysteine during Phenotypic
      Reversal.
AB  - [This retracts the article DOI: 10.1155/2014/479180.].

PMID- 27689079
TI  - Effects of Betaine Aldehyde Dehydrogenase-Transgenic Soybean on Phosphatase
      Activities and Rhizospheric Bacterial Community of the Saline-Alkali Soil.
AB  - The development of transgenic soybean has produced numerous economic benefits;
      however the potential impact of root exudates upon soil ecological systems and
      rhizospheric soil microbial diversity has also received intensive attention. In
      the present study, the influence of saline-alkali tolerant transgenic soybean of
      betaine aldehyde dehydrogenase on bacterial community structure and soil
      phosphatase during growth stages was investigated. The results showed that,
      compared with nontransgenic soybean as a control, the rhizospheric soil pH of
      transgenic soybean significantly decreased at the seedling stage. Compared to
      HN35, organic P content was 13.5% and 25.4% greater at the pod-filling stage and
      maturity, respectively. The acid phosphatase activity of SRTS was significantly
      better than HN35 by 12.74% at seedling, 14.03% at flowering, and 59.29% at
      podding, while alkaline phosphatase achieved maximum activity in the flowering
      stage and was markedly lower than HN35 by 13.25% at pod-filling. The 454
      pyrosequencing technique was employed to investigate bacterial diversity, with a
      total of 25,499 operational taxonomic units (OTUs) obtained from the 10 samples.
      Notably, the effect of SRTS on microbial richness and diversity of rhizospheric
      soil was marked at the stage of podding and pod-filling. Proteobacteria,
      Acidobacteria, and Actinobacteria were the dominant phyla among all samples.
      Compared with HN35, the relative abundance of Proteobacteria was lower by 2.01%,
      2.06%, and 5.28% at the stage of seedling, at pod-bearing, and at maturity. In
      genus level, the relative abundance of Gp6, Sphingomonas sp., and GP4 was
      significantly inhibited by SRTS at the stage of pod-bearing and pod-filling.

PMID- 27689078
TI  - Can Molecular Biomarkers Change the Paradigm of Pancreatic Cancer Prognosis?
AB  - Pancreatic ductal adenocarcinoma is one of the most lethal types of tumour, and
      its incidence is rising worldwide. Although survival can be improved when these
      tumours are detected at an early stage, this cancer is usually asymptomatic, and
      the disease only becomes apparent after metastasis. The only prognostic biomarker
      approved by the FDA to date is carbohydrate antigen 19-9 (CA19-9); however, the
      specificity of this biomarker has been called into question, and diagnosis is
      usually based on clinical parameters. Tumour size, degree of differentiation,
      lymph node status, presence of distant metastasis at diagnosis, protein levels of
      KI-67 or C-reactive protein, and mutational status of P53, KRAS, or BRCA2 are the
      most useful biomarkers in clinical practice. In addition to these, recent
      translational research has provided evidence of new biomarkers based on different
      molecules involved in endoplasmic reticulum stress, epithelial-to-mesenchymal
      transition, and noncoding RNA panels, especially microRNAs and long noncoding
      RNAs. These new prospects open new paths to tumour detection using minimally or
      noninvasive techniques such as liquid biopsies. To find sensitive and specific
      biomarkers to manage these patients constitutes a challenge for the research
      community and for public health policies.

PMID- 27689082
TI  - Efficacy and Safety of LASIK Combined with Accelerated Corneal Collagen Cross
      Linking for Myopia: Six-Month Study.
AB  - This was a prospective controlled clinical trial. 48 myopia patients (96 eyes)
      were included in this study. After LASIK, accelerated corneal collagen cross
      linking (ACXL) was used for myopia treatment. During 6-month follow-up, the
      results of LASIK-ACXL treatment were studied and compared to the LASIK-only
      procedure. The results showed that no statistically significant differences in
      UDVA, CDVA, MRSE, K mean, pachymetry, or ECD were found between the two groups at
      the visit after 6 months of follow-up (all P > 0.05). At 6 months
      postoperatively, 2 eyes lost one or more lines of visual acuity in the LASIK-ACXL
      group, whereas all LASIK-only treated eyes had a stable CDVA. In vivo confocal
      microscopy showed a decrease of keratocyte density and appearance of honeycomb
      like structures in the anterior residual stroma bed; the changes were similar but
      more pronounced following LASIK-only. None of the cases in both groups developed
      signs of significant keratitis, regression, or ectasia during the 6-month follow
      up. LASIK-ACXL can effectively correct refractive error in patients with myopia,
      with no significant complications during 6-month follow-up, indicating stability
      and morphologic change similar to those with LASIK-only treatment.

PMID- 27689081
TI  - Potential Effects of Corneal Cross-Linking upon the Limbus.
AB  - Corneal cross-linking is nowadays the most used strategy for the treatment of
      keratoconus and recently it has been exploited for an increasing number of
      different corneal pathologies, from other ectatic disorders to keratitis. The
      safety of this technique has been widely assessed, but clinical complications
      still occur. The potential effects of cross-linking treatment upon the limbus are
      incompletely understood; it is important therefore to investigate the effect of
      UV exposure upon the limbal niche, particularly as UV is known to be mutagenic to
      cellular DNA and the limbus is where ocular surface tumors can develop. The risk
      of early induction of ocular surface cancer is undoubtedly rare and has to date
      not been published other than in one case after cross-linking. Nevertheless it is
      important to further assess, understand, and reduce where possible any potential
      risk. The aim of this review is to summarize all the reported cases of a
      pathological consequence for the limbal cells, possibly induced by cross-linking
      UV exposure, the studies done in vitro or ex vivo, the theoretical bases for the
      risks due to UV exposure, and which aspects of the clinical treatment may produce
      higher risk, along with what possible mechanisms could be utilized to protect the
      limbus and the delicate stem cells present within it.

PMID- 27689085
TI  - Retracted: Superoxide-Dismutase Deficient Mutants in Common Beans (Phaseolus
      vulgaris L.): Genetic Control, Differential Expressions of Isozymes, and
      Sensitivity to Arsenic.
AB  - [This retracts the article DOI: 10.1155/2013/782450.].

PMID- 27689083
TI  - Meta-Analysis of the Association between Vitiligo and Human Leukocyte Antigen-A.
AB  - Objective. The objective of this study was to systematically evaluate the
      association between vitiligo and human leukocyte antigen- (HLA-) A. Methods.
      PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and
      reference lists were searched for relevant original articles. Results. Nineteen
      case-control studies comprising 3042 patients and 5614 controls were included, in
      which 33 HLA-A alleles were reported. Overall, three alleles (HLA-A*02, A*33, and
      Aw*31) were significantly associated with increased risk of vitiligo, two (HLA
      A*09 and Aw*19) were associated with decreased risk, and the remaining 28 were
      unassociated. Twelve alleles, seven alleles, and 19 alleles were common to three
      ethnicities, both types of vitiligo, and both typing methods, respectively. In
      the subgroup analysis by ethnicity and typing methods, the association of six
      alleles and five alleles was inconsistent in three populations and both typing
      methods, respectively. In the subgroup analysis by clinical type, the association
      of all seven alleles was consistent in both types of vitiligo. Conclusion. The
      meta-analysis suggests that HLA-A*02, A*33, and Aw*31 are associated with
      increased risk of vitiligo, while HLA-A*09 and Aw*19 are associated with
      decreased risk of vitiligo. The association of some alleles varies in terms of
      ethnicity and typing methods.

PMID- 27689084
TI  - Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of
      Human and Mouse.
AB  - Genetic networks provide new mechanistic insights into the diversity of species
      morphology. In this study, we have integrated the MGI, GEO, and miRNA database to
      analyze the genetic regulatory networks under morphology difference of integument
      of humans and mice. We found that the gene expression network in the skin is
      highly divergent between human and mouse. The GO term of secretion was highly
      enriched, and this category was specific in human compared to mouse. These
      secretion genes might be involved in eccrine system evolution in human. In
      addition, total 62,637 miRNA binding target sites were predicted in human
      integument genes (IGs), while 26,280 miRNA binding target sites were predicted in
      mouse IGs. The interactions between miRNAs and IGs in human are more complex than
      those in mouse. Furthermore, hsa-miR-548, mmu-miR-466, and mmu-miR-467 have an
      enormous number of targets on IGs, which both have the role of inhibition of host
      immunity response. The pattern of distribution on the chromosome of these three
      miRNAs families is very different. The interaction of miRNA/IGs has added the new
      dimension in traditional gene regulation networks of skin. Our results are
      generating new insights into the gene networks basis of skin difference between
      human and mouse.

PMID- 27689086
TI  - The Effect of Advanced Motherhood on Newborn Offspring's Hippocampal Neural Stem
      Cell Proliferation.
AB  - Objective. To investigate the effect of advanced motherhood on rat hippocampal
      neural stem cell proliferation. Methods. Female parents were subdivided into
      control and old mother group by age, and neural stem cells were cultured from
      hippocampal tissues for 24 h newborn offspring. The diameter and numbers of
      neurospheres were examined by microscopy, and differences in proliferation were
      examined by EdU immunofluorescence, CCK-8 assay, and cell cycle analysis.
      Results. The number of neurospheres in the old mother group after culture was
      lower than the control group. Additionally, neurospheres' diameter was smaller
      than that of the control group (P < 0.05). The EdU positive rate of the old
      mother group was lower than that of the control group (P < 0.05). CCK-8 assay
      results showed that the absorbance values for the old mother group were lower
      than that of the control group at 48 h and 72 h (P < 0.05). The proportions of
      cells in the S and G2/M phases of the cell cycle for the older mother group were
      less than that found for the control group (P < 0.05). Conclusion. The
      proliferation rates of hippocampal NSCs seen in the older mother group were lower
      than that seen in the control group.

PMID- 27689087
TI  - rLj-RGD3, a Novel Three-RGD-Motif-Containing Recombinant Protein from Lampetra
      japonica, Protects PC12 Cells from Injury Induced by Oxygen-Glucose Deprivation
      and Reperfusion.
AB  - rLj-RGD3 is a 14.5 kDa recombinant protein with 3 RGD (Arg-Gly-Asp) motifs from
      the salivary gland secretions of Lampetra japonica, which is a histidine-rich and
      arginine-rich protein. Previous reports indicated that rLj-RGD3 has typical
      functions of RGD-toxin protein, such as platelet aggregation suppression tumour
      metastasis and angiogenesis inhibition. Because histidine and arginine have
      cerebral ischemia-reperfusion and neuroprotective functions, we investigated
      whether rLj-RGD3 has such activities and studied the mechanism. The effects of
      rLj-RGD3 on neuroprotection and antiapoptosis were determined. The expression
      level of focal adhesion kinase (FAK), p-FAK, Caspase-3, and Bcl-2 after oxygen
      glucose deprivation and reperfusion (OGD-R) was examined. The viability of PC12
      cells incubated with rLj-RGD3 at high concentrations (16 MUmol/L) increased
      significantly due to its ability to protect the cells from apoptosis after OGD-R
      induced injury. Furthermore, rLj-RGD3 attenuated the damage due to OGD-R. Most of
      the PC12 cells were apoptotic after OGD-R. In contrast, the number of apoptotic
      PC12 cells was significantly decreased in the group treated with a high-dose of
      rLj-RGD3. In addition, rLj-RGD3 activated FAK and p-FAK protein. rLj-RGD3
      inhibited Caspase-3 and upregulated Bcl-2 protein expression in PC12 cells after
      OGD-R. The study provides the first evidence for neuroprotective effects of rLj
      RGD3 in ischemic injury that may be partly mediated through inhibition of Caspase
      3 and upregulation of Bcl-2, FAK, and p-FAK protein expression.

PMID- 27689089
TI  - New Trends of Digital Data Storage in DNA.
AB  - With the exponential growth in the capacity of information generated and the
      emerging need for data to be stored for prolonged period of time, there emerges a
      need for a storage medium with high capacity, high storage density, and
      possibility to withstand extreme environmental conditions. DNA emerges as the
      prospective medium for data storage with its striking features. Diverse encoding
      models for reading and writing data onto DNA, codes for encrypting data which
      addresses issues of error generation, and approaches for developing codons and
      storage styles have been developed over the recent past. DNA has been identified
      as a potential medium for secret writing, which achieves the way towards DNA
      cryptography and stenography. DNA utilized as an organic memory device along with
      big data storage and analytics in DNA has paved the way towards DNA computing for
      solving computational problems. This paper critically analyzes the various
      methods used for encoding and encrypting data onto DNA while identifying the
      advantages and capability of every scheme to overcome the drawbacks identified
      priorly. Cryptography and stenography techniques have been analyzed in a critical
      approach while identifying the limitations of each method. This paper also
      identifies the advantages and limitations of DNA as a memory device and memory
      applications.

PMID- 27689090
TI  - Robust Individual-Cell/Object Tracking via PCANet Deep Network in Biomedicine and
      Computer Vision.
AB  - Tracking individual-cell/object over time is important in understanding drug
      treatment effects on cancer cells and video surveillance. A fundamental problem
      of individual-cell/object tracking is to simultaneously address the cell/object
      appearance variations caused by intrinsic and extrinsic factors. In this paper,
      inspired by the architecture of deep learning, we propose a robust feature
      learning method for constructing discriminative appearance models without large
      scale pretraining. Specifically, in the initial frames, an unsupervised method is
      firstly used to learn the abstract feature of a target by exploiting both classic
      principal component analysis (PCA) algorithms with recent deep learning
      representation architectures. We use learned PCA eigenvectors as filters and
      develop a novel algorithm to represent a target by composing of a PCA-based
      filter bank layer, a nonlinear layer, and a patch-based pooling layer,
      respectively. Then, based on the feature representation, a neural network with
      one hidden layer is trained in a supervised mode to construct a discriminative
      appearance model. Finally, to alleviate the tracker drifting problem, a sample
      update scheme is carefully designed to keep track of the most representative and
      diverse samples during tracking. We test the proposed tracking method on two
      standard individual cell/object tracking benchmarks to show our tracker's state
      of-the-art performance.

PMID- 27689091
TI  - Anaerobic Codigestion of Municipal Wastewater Treatment Plant Sludge with Food
      Waste: A Case Study.
AB  - The aim of this study was to assess the effects of the codigestion of food
      manufacturing and processing wastes (FW) with sewage sludge (SS), that is,
      municipal wastewater treatment plant primary sludge and waste activated sludge.
      Bench scale mesophilic anaerobic reactors were fed intermittently with varying
      ratio of SS and FW and operated at a hydraulic retention time of 20 days and
      organic loading of 2.0 kg TS/m3.d. The specific biogas production (SBP) increased
      by 25% to 50% with the addition of 1%-5% FW to SS which is significantly higher
      than the SBP from SS of 284 +/- 9.7 mLN/g VS added. Although the TS, VS, and tCOD
      removal slightly increased, the biogas yield and methane content improved
      significantly and no inhibitory effects were observed as indicated by the stable
      pH throughout the experiment. Metal screening of the digestate suggested the
      biosolids meet the guidelines for use as a soil conditioner. Batch biochemical
      methane potential tests at different ratios of SS : FW were used to determine the
      optimum ratio using surface model analysis. The results showed that up to 47-48%
      FW can be codigested with SS. Overall these results confirm that codigestion has
      great potential in improving the methane yield of SS.

PMID- 27689088
TI  - Influence of Botulinumtoxin A on the Expression of Adult MyHC Isoforms in the
      Masticatory Muscles in Dystrophin-Deficient Mice (Mdx-Mice).
AB  - The most widespread animal model to investigate Duchenne muscular dystrophy is
      the mdx-mouse. In contrast to humans, phases of muscle degeneration are replaced
      by regeneration processes; hence there is only a restricted time slot for
      research. The aim of the study was to investigate if an intramuscular injection
      of BTX-A is able to break down muscle regeneration and has direct implications on
      the gene expression of myosin heavy chains in the corresponding treated and
      untreated muscles. Therefore, paralysis of the right masseter muscle was induced
      in adult healthy and dystrophic mice by a specific intramuscular injection of BTX
      A. After 21 days the mRNA expression and protein content of MyHC isoforms of the
      right and left masseter, temporal, and the tongue muscle were determined using
      quantitative RT-PCR and Western blot technique. MyHC-IIa and MyHC-I-mRNA
      expression significantly increased in the paralyzed masseter muscle of control
      mice, whereas MyHC-IIb and MyHC-IIx/d-mRNA were decreased. In dystrophic muscles
      no effect of BTX-A could be detected at the level of MyHC. This study suggests
      that BTX-A injection is a suitable method to simulate DMD-pathogenesis in healthy
      mice but further investigations are necessary to fully analyse the BTX-A effect
      and to generate sustained muscular atrophy in mdx-mice.

PMID- 27689092
TI  - Aberrant LncRNA Expression Profile in a Contusion Spinal Cord Injury Mouse Model.
AB  - Long noncoding RNAs (LncRNAs) play a crucial role in cell growth, development,
      and various diseases related to the central nervous system. However, LncRNA
      differential expression profiles in spinal cord injury are yet to be reported. In
      this study, we profiled the expression pattern of LncRNAs using a microarray
      method in a contusion spinal cord injury (SCI) mouse model. Compared with a
      spinal cord without injury, few changes in LncRNA expression levels were noted 1
      day after injury. The differential changes in LncRNA expression peaked 1 week
      after SCI and subsequently declined until 3 weeks after injury. Quantitative real
      time polymerase chain reaction (qRT-PCR) was used to validate the reliability of
      the microarray, demonstrating that the results were reliable. Gene ontology (GO)
      analysis indicated that differentially expressed mRNAs were involved in
      transport, cell adhesion, ion transport, and metabolic processes, among others.
      Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that
      the neuroactive ligand-receptor interaction, the PI3K-Akt signaling pathway, and
      focal adhesions were potentially implicated in SCI pathology. We constructed a
      dynamic LncRNA-mRNA network containing 264 LncRNAs and 949 mRNAs to elucidate the
      interactions between the LncRNAs and mRNAs. Overall, the results from this study
      indicate for the first time that LncRNAs are differentially expressed in a
      contusion SCI mouse model.

PMID- 27689093
TI  - Angiogenic Effects of Collagen/Mesoporous Nanoparticle Composite Scaffold
      Delivering VEGF165.
AB  - Vascularization is a key issue for the success of tissue engineering to repair
      damaged tissue. In this study, we report a composite scaffold delivering
      angiogenic factor for this purpose. Vascular endothelial growth factor (VEGF) was
      loaded on mesoporous silica nanoparticle (MSN), which was then incorporated
      within a type I collagen sponge, to produce collagen/MSN/VEGF (CMV) scaffold. The
      CMV composite scaffold could release VEGF sustainably over the test period of 28
      days. The release of VEGF improved the cell proliferation. Moreover, the in vivo
      angiogenesis of the scaffold, as studied by the chick chorioallantoic membrane
      (CAM) model, showed that the VEGF-releasing scaffold induced significantly
      increased number of blood vessel complexes when compared with VEGF-free scaffold.
      The composite scaffold showed good biocompatibility, as examined in rat
      subcutaneous tissue. These results demonstrate that the CMV scaffold with VEGF
      releasing capacity can be potentially used to stimulate angiogenesis and tissue
      repair.

PMID- 27689094
TI  - Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and
      Their Application in the Treatment of Multidrug-Resistant Bacteria.
AB  - Levofloxacin is a synthetic broad-spectrum antibacterial agent for oral or
      intravenous administration. Chemically, levofloxacin is the levorotatory isomer
      (L-isomer) of racemate ofloxacin, a fluoroquinolone antibacterial agent.
      Quinolone derivatives rapidly and specifically inhibit the synthesis of bacterial
      DNA. Levofloxacin has in vitro activity against a broad range of aerobic and
      anaerobic Gram-positive and Gram-negative bacteria. However, formulation of
      combined poloxamers thermoregulated (as Pluronic(r) F127) and levofloxacin for
      use in multiresistant bacterial treatment were poorly described in the current
      literature. Thus, the aim of the present work is to characterize poloxamers for
      levofloxacin controlled release and their use in the treatment of multidrug
      bacterial resistance. Micelles were produced in colloidal dispersions, with a
      diameter between 5 and 100 nm, which form spontaneously from amphiphilic
      molecules under certain conditions as concentration and temperature.
      Encapsulation of levofloxacin into nanospheres showed efficiency and enhancement
      of antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and
      Klebsiella pneumoniae when compared with only levofloxacin. Furthermore, all
      formulations were not cytotoxic for NIH/3T3 cell lineage. In conclusion,
      poloxamers combined with levofloxacin have shown promising results, better than
      alone, decreasing the minimal inhibitory concentration of the studied bacterial
      multiresistance strains. In the future, this new formulation will be used after
      being tested in animal models in patients with resistant bacterial strains.

PMID- 27689096
TI  - Development and Validation of a Simple Risk Score for Undiagnosed Type 2 Diabetes
      in a Resource-Constrained Setting.
AB  - Objective. To develop and validate a risk score for detecting cases of
      undiagnosed diabetes in a resource-constrained country. Methods. Two population
      based studies in Peruvian population aged >=35 years were used in the analysis:
      the ENINBSC survey (n = 2,472) and the CRONICAS Cohort Study (n = 2,945). Fasting
      plasma glucose >=7.0 mmol/L was used to diagnose diabetes in both studies.
      Coefficients for risk score were derived from the ENINBSC data and then the
      performance was validated using both baseline and follow-up data of the CRONICAS
      Cohort Study. Results. The prevalence of undiagnosed diabetes was 2.0% in the
      ENINBSC survey and 2.9% in the CRONICAS Cohort Study. Predictors of undiagnosed
      diabetes were age, diabetes in first-degree relatives, and waist circumference.
      Score values ranged from 0 to 4, with an optimal cutoff >=2 and had a moderate
      performance when applied in the CRONICAS baseline data (AUC = 0.68; 95% CI: 0.62
      0.73; sensitivity 70%; specificity 59%). When predicting incident cases, the AUC
      was 0.66 (95% CI: 0.61-0.71), with a sensitivity of 69% and specificity of 59%.
      Conclusions. A simple nonblood based risk score based on age, diabetes in first
      degree relatives, and waist circumference can be used as a simple screening tool
      for undiagnosed and incident cases of diabetes in Peru.

PMID- 27689097
TI  - Structural and Functional Characterization of Recombinant Interleukin-10 from
      Indian Major Carp Labeo rohita.
AB  - Interleukin-10, an important regulator of both the innate and adaptive immune
      systems, is a multifunctional major cytokine. Though it is one of the major
      cytokines, IL-10 from the Indian major carp, Labeo rohita, has not yet been
      characterized. In the present study, we report large scale production and
      purification of biologically active recombinant IL-10 of L. rohita (rLrIL-10)
      using a heterologous expression system and its biophysical and functional
      characterization. High yield (~70 mg/L) of soluble rLrIL-10 was obtained at shake
      flask level. The rLrIL-10 was found to exist as a dimer. Far-UV CD spectroscopy
      showed presence of predominantly alpha helices. The tertiary structure of the
      purified rLrIL-10 was verified by fluorescence spectroscopy. Two-dimensional gel
      analysis revealed the presence of six isoforms of the rLrIL-10. The rLrIL-10 was
      biologically active and its administration significantly reduced serum
      proinflammatory cytokines, namely, interleukin 1beta, TNFalpha, and IL-8, and
      augmented the NKEF transcript levels in spleen of L. rohita. Anti-inflammatory
      role of the rLrIL-10 was further established by inhibition of phagocytosis using
      NBT reduction assay in vitro. The data indicate that the dimeric alpha helical
      structure and function of IL-10 of L. rohita as a key regulator of anti
      inflammatory response have remained conserved during evolution.

PMID- 27689098
TI  - Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley
      Fever: A Review Study.
AB  - Rift Valley Fever (RVF) is an infectious illness with serious clinical
      manifestations and health consequences in humans as well as a wide range of
      domestic ruminants. This review provides significant information about the
      prevention options of RVF along with the safety-efficacy profile of commercial
      vaccines and some of RVF vaccination strategies. Information presented in this
      paper was obtained through a systematic investigation of published data about RVF
      vaccines. Like other viral diseases, the prevention of RVF relies heavily on
      immunization of susceptible herds with safe and cost-effective vaccine that is
      able to confer long-term protective immunity. Several strains of RVF vaccines
      have been developed and are available in commercial production including Formalin
      Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent
      Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn
      vaccine are immunogenic and widely used in prevention programs, they proved to be
      accompanied by significant concerns. Despite Clone13 vaccine being suggested as
      safe in pregnant ewes and as highly immunogenic along with its potential for
      differentiating infected from vaccinated animals (DIVA), a recent study raised
      concerns about the safety of the vaccine during the first trimester of gestation.
      Accordingly, RVF vaccines that are currently available in the market to a
      significant extent do not fulfill the requirements of safety, potency, and DIVA.
      These adverse effects stressed the need for developing new vaccines with an
      excellent safety profile to bridge the gap in safety and immunity. Bringing RVF
      vaccine candidates to local markets besides the absence of validated serological
      test for DIVA remain the major challenges of RVF control.

PMID- 27689095
TI  - Key Challenges and Opportunities Associated with the Use of In Vitro Models to
      Detect Human DILI: Integrated Risk Assessment and Mitigation Plans.
AB  - Drug-induced liver injury (DILI) is a major cause of late-stage clinical drug
      attrition, market withdrawal, black-box warnings, and acute liver failure.
      Consequently, it has been an area of focus for toxicologists and clinicians for
      several decades. In spite of considerable efforts, limited improvements in DILI
      prediction have been made and efforts to improve existing preclinical models or
      develop new test systems remain a high priority. While prediction of intrinsic
      DILI has improved, identifying compounds with a risk for idiosyncratic DILI
      (iDILI) remains extremely challenging because of the lack of a clear mechanistic
      understanding and the multifactorial pathogenesis of idiosyncratic drug
      reactions. Well-defined clinical diagnostic criteria and risk factors are also
      missing. This paper summarizes key data interpretation challenges, practical
      considerations, model limitations, and the need for an integrated risk
      assessment. As demonstrated through selected initiatives to address other types
      of toxicities, opportunities exist however for improvement, especially through
      better concerted efforts at harmonization of current, emerging and novel in vitro
      systems or through the establishment of strategies for implementation of
      preclinical DILI models across the pharmaceutical industry. Perspectives on the
      incorporation of newer technologies and the value of precompetitive consortia to
      identify useful practices are also discussed.

PMID- 27689100
TI  - Daptomycin-Vancomycin-Resistant Enterococcus faecium Native Valve Endocarditis:
      Successfully Treated With Off-Label Quinupristin-Dalfopristin.
AB  - Multidrug-resistant enterococcal nosocomial invasive infections are a rising
      concern faced by the medical community. Not many options are available to treat
      these highly virulent organisms. Risk factors for developing these highly
      resistant organisms include prolonged hospital stay, previous antibiotic use, and
      immunosuppression. In this article, we report a case of daptomycin-resistant
      enterococcal native infective endocarditis treated with off-label use of
      quinupristin-dalfopristin. 

PMID- 27689101
TI  - Expression mediated by three partial sequences of the human tyrosine hydroxylase
      promoter in vivo.
AB  - The use of viral vectors to transfect postmitotic neurons has provided an
      important research tool, and it offers promise for treatment of neurologic
      disease. The utility of vectors is enhanced by the use of selective promoters
      that permit control of the cellular site of expression. One potential clinical
      application is in the neurorestorative treatment of Parkinson's disease by the
      induction of new axon growth. However, many of the genes with an ability to
      restore axons have oncogenic potential. Therefore, clinical safety would be
      enhanced by restriction of expression to neurons affected by the disease,
      particularly dopamine neurons. To achieve this goal we have evaluated in vivo
      three partial sequences of the promoter for human tyrosine hydroxylase, the rate
      limiting enzyme in catecholamine synthesis. All sequences induced expression in
      dopamine neurons. None of them induced expression in glia or in nondopaminergic
      neurons in striatum or cortex. We conclude that these sequences have potential
      use for targeting dopamine neurons in research and clinical applications. 

PMID- 27689102
TI  - Bronchopulmonary Dysplasia in Preterm Infants Born at Less Than 32 Weeks
      Gestation.
AB  - OBJECTIVES: Bronchopulmonary dysplasia (BPD) is a chronic pulmonary disorder
      affecting preterm infants. We studied the factors and echocardiographic evidence
      of early pulmonary hypertension (PH) associated with moderate or severe BPD.
      METHODS: We retrospectively reviewed preterm infants who were born at <32 weeks
      gestation and admitted to the neonatal intensive care unit at the Children's
      Hospital of Zhejiang University School of Medicine between July 2013 and July
      2015. RESULTS: Forty-two preterm infants were enrolled in the study. All the
      patients received oxygen treatment for a mean of 62.5 +/- 28.0 days. The grades
      of BPD were classified as follows: severe, 35.7%; moderate, 40.5%; and mild,
      23.8%. The time of ventilator and oxygen supplementation was longer in infants
      who developed PH. Severe BPD was related to PH at 28 days. CONCLUSIONS: These
      findings support the notion that early pulmonary vascular disease and long-term
      infection in preterm infants contributes to increased susceptibility for severe
      BPD.

PMID- 27689099
TI  - Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery
      Vehicle for Norovirus Virus-Like Particles.
AB  - We have recently shown that tubular form of rotavirus (RV) recombinant VP6
      protein has an in vivo adjuvant effect on the immunogenicity of norovirus (NoV)
      virus-like particle (VLP) vaccine candidate. In here, we investigated in vitro
      effect of VP6 on antigen presenting cell (APC) activation and maturation and
      whether VP6 facilitates NoV VLP uptake by these APCs. Mouse macrophage cell line
      RAW 264.7 and dendritic cell line JAWSII were used as model APCs. Internalization
      of VP6, cell surface expression of CD40, CD80, CD86, and major histocompatibility
      class II molecules, and cytokine and chemokine production were analyzed. VP6
      nanotubes were efficiently internalized by APCs. VP6 upregulated the expression
      of cell surface activation and maturation molecules and induced secretion of
      several proinflammatory cytokines and chemokines. The mechanism of VP6 action was
      shown to be partially dependent on lipid raft-mediated endocytic pathway as shown
      by methyl-beta-cyclodextrin inhibition on tumor necrosis factor alpha secretion.
      These findings add to the understanding of mechanism by which VP6 exerts its
      immunostimulatory and immunomodulatory actions and further support its use as a
      part of nonlive RV-NoV combination vaccine.

PMID- 27689103
TI  - Small Steps in Impacting Clinical Auscultation of Medical Students.
AB  - The objective of this study was to determine if a training module improves the
      auscultation skills of medical students at the University of Maryland School of
      Medicine. Second-year medical students completed pretests on 12 heart sounds
      followed by a 45-minute training module on clinical auscultation, with retesting
      immediately after the intervention and during their third-year pediatrics
      clerkship. The control group consisted of third-year medical students who did not
      have the intervention. There was a 23% improvement in the identification of heart
      sounds postintervention (P < .001). Diastolic and valvular murmurs were poorly
      identified pre- and post intervention. There was a 6% decline in accuracy of the
      intervention group in the following academic year. The intervention group was
      superior to the control group at identifying the tested heart sounds (49% vs 43%,
      P = .04). The accuracy of second-year medical students in identifying heart
      sounds improved after a brief training module. 

PMID- 27689104
TI  - Early prediction of renal parenchymal injury with serum procalcitonin.
AB  - INTRODUCTION: Urinary tract infection (UTI) is one of the most common bacterial
      infections in children that can be associated with renal parenchymal injuries and
      late scars. Dimercaptosuccinic acid (DMSA) renal scan is known as golden standard
      for detecting acute pyelonephritis (APN) that has a lot of difficulties and
      limitations. OBJECTIVES: we designed this study the accuracy of one inflammatory
      marker, serum procalcitonin (PCT) to identify as an early predictor of renal
      injuries. PATIENTS AND METHODS: A prospective study was carried out in 95
      patients who admitted in the hospital with the first febrile UTI. Serum PCT of
      all patients was measured; sensitivity, specificity, positive and negative
      predictive value (PPV and NPV) of this marker was analyzed compared to DMSA scan.
      P value <0.05 was taken as significant. RESULTS: In total, 79 females and 16
      males were investigated. There are 42 cases in group 1 with normal DMSA scan and
      53 patients in group two with renal parenchymal injuries in their scans. Mann
      Whitney test showed a meaningful relation between the two groups regarding PCT
      level (P<0.0001). Sensitivity, specificity, PPV and NPV of PCT reported in
      optimum cut off were 70%, 88.1%, 88.1% and 70%, respectively. The positive
      likelihood ratio (PLR) of PCT test was 5.8. CONCLUSION: In the current survey,
      PCT was the eligible inflammatory marker to predict renal parenchymal injuries in
      children with proper sensitivity, specificity, PPV and NPV that play also a
      pivotal role in the children aged less than 24 months, although, more studies
      should be undertaken to confirm.

PMID- 27689105
TI  - Correlation between serum leptin and bone mineral density in hemodialysis
      patients.
AB  - INTRODUCTION: For diagnosing of specific types of bone lesions in hemodialysis
      (HD) patients, it is necessary to conduct a bone biopsy as the gold standard
      method. However, it is an invasive procedure. While different markers have been
      suggested as alternative methods, none of them has been selected. The frequency
      of hip fractures is 80 fold in HD patients who have two-fold mortality as
      compared with general population. OBJECTIVES: Recently, serum leptin has been
      suggested as a bone density marker. This study tries to confirm this proposal.
      PATIENTS AND METHODS: In this study about 104 HD patients (53.8% male and 46.2%
      female) were enrolled. The average age was 38.28+/-7.89 years. Serum leptin, bone
      alkaline phosphatase, intact parathyroid hormone (iPTH), 25(OH)D, calcium,
      phosphorus and bone mineral density (BMD) (at the femoral neck and lumbar spine,
      as measured by dual-energy x-ray absorptiometry [DXA]) were assessed. RESULTS:
      Analysis by polynomial regression revealed no correlation between BMD Z-score at
      two points and serum leptin level. According to the thresholds of 25 ng/mL and 18
      24 ng/mL in some studies, we detected 25 ng/mL as the threshold in our patients.
      Under this threshold, the leptin effect on bone mass was negative, and above the
      threshold of 25 ng/mL, we found leptin had positive effect on bone mass.
      CONCLUSION: In this investigation, we found, leptin has a bimodal effect on bone
      mass. Cortical bones assessment may be a better option for assessment.

PMID- 27689106
TI  - The evaluation of relationship between blood pressure and dialysate Na
      concentration in chronic hemodialysis patients.
AB  - INTRODUCTION: Hypertension is one of the traditional risk factors of
      cardiovascular disease (CVD). Extra cellular volume expansion and Na retention
      remain the main cause of hypertension. OBJECTIVES: The aim of this study was to
      investigate the relation between concentration of Na dialysate and blood pressure
      (BP) in chronic hemodialysis (HD) patient. PATIENTS AND METHODS: This cross
      sectional study was performed on 266 adult patients undergoing HD for at least
      three months. Pre-HD systolic BP (SBP) and post-HD SBP during 4 weeks were
      measured in relation to Na dialysate concentration. The other main factors
      affecting the post-dialysis BP, such as body mass index (BMI), pump speed,
      dialysis solution temperature, duration of dialysis and intradialysis weight gain
      (IDWG) were also considered. Mean of DeltaSBP (post-HD SBP - pre-HD SBP) in each
      patient in 12 session of HD was measured and statistically analyzed in relation
      to dialysate Na with SPSS 21. Backward multivariable linear regression analysis
      and Pearson's correlation coefficients were used to evaluate the correlation
      between sodium gradient and DeltaSBP. RESULTS: SBP was significantly changed
      before and after dialysis in relation to dialysate Na (P<0.001). The Pearson's
      correlation between DeltaSBP with dialysate sodium and blood flow rate (pump
      speed) were statistically significant(P<0.05). CONCLUSION: We found that changes
      in SBP before and after dialysis is significantly associated with dialysate
      sodium concentration.

PMID- 27689107
TI  - An ethnobotanical study of medicinal plants administered for the treatment of
      hypertension.
AB  - INTRODUCTION: The incidence of cardiovascular diseases (CVDs) is very high in
      human societies and their prevention and treatment are the most important
      priority in many countries. Hypertension makes an important contribution to the
      development of CVDs. OBJECTIVES: This study aimed to collect the ethno-medicinal
      knowledge of the traditional healers of Shiraz on medicinal plants used in the
      treatment of hypertension. MATERIALS AND METHODS: Ethno-medicinal data were
      collected from September 2012 to July 2013 through direct interview. Twenty-five
      healers were interviewed using semi-structured questionnaires and their
      traditional ethno-medicinal knowledge was recorded. Questionnaires were included
      apothecary personal information, plant local name, plant parts used, method of
      preparation, season of harvest and traditional use. Data collected from surveys
      and interviews were transferred to Microsoft Excel 2007 and analyzed. RESULTS:
      Analysis of data showed that, 27 medicinal plants from 22 families are used for
      the treatment of hypertension. The families with most antihypertensive species
      were Apiaceae (8%), Rosaceae (8%) and Papaveraceae (8%). The most frequently used
      plant parts were leaves (36%) followed by fruits (30%), aerial part (17%) and
      branches (7%). The most frequently used preparation method was decoction (95%).
      Borago officinalis (51.85%), Berberis vulgaris (51.58%) had the highest frequency
      of mention. CONCLUSION: The ethno-medicinal survey of medicinal plants
      recommended by traditional healers for the treatment of hypertension provides new
      areas of research on the antihypertensive effect of medicinal plants. In the case
      of safety and effectiveness, they can be refined and processed to produce natural
      drugs.

PMID- 27689108
TI  - Identification of medicinal plants for the treatment of kidney and urinary
      stones.
AB  - INTRODUCTION: Kidney stones are the third most common urinary tract problems
      after urinary tract infections and prostate pathology. Kidney stones may cause
      extreme pain and blockage of urine flow. They are usually treated with
      medications that may cause a number of side-effects. Medicinal herbs are used in
      different cultures as a reliable source of natural remedies. OBJECTIVES: This
      study aimed to determine native medicinal plants used by traditional healers of
      Shiraz for the treatment of kidney stones. MATERIALS AND METHODS: The ethno
      medicinal data were collected between July and September 2012 through face-to
      face interview with local herbalist. RESULTS: A total of 18 species belonging to
      19 botanical families were recorded in study area. Species with the highest
      frequency of mentions were Alhagi maurorum (51.58%), Tribulus terrestris
      (51.58%), and Nigella sativa (48.14). The most frequently used plant parts were
      aerial parts (38%), leaf (33%) and fruits (17%). Decoction (68%) was the most
      frequently prescribed method of preparation. Most of the medicinal plants
      recommended by Shirazian herbalists have not been investigated in animal and
      humane models of renal stone which provides a new area of research. CONCLUSION:
      In the case of safety and effectiveness, they can be refined and processed to
      produce natural drugs.

PMID- 27689109
TI  - High doses of oral folate and sublingual vitamin B12 in dialysis patients with
      hyperhomocysteinemia.
AB  - INTRODUCTION: Folic acid and vitamin B12, alone or in combination have been used
      to reduce homocysteine (Hcy) levels in dialysis patients. OBJECTIVES: We aimed to
      assess the efficacy of high doses of oral folate and vitamin B12 in reducing
      plasma Hcy levels after a 12-week treatment. PATIENTS AND METHODS: Thirty-two
      dialysis patients aged 10-324 months screened for hyperhomocysteinuria. Then
      cases with hyperhomocysteinemia received oral folate 10 mg/day with sublingual
      methylcobalamin 1 mg/day for 12 weeks. In pre- and post-intervention phases
      plasma Hcy concentration, serum folate, and vitamin B12 levels were measured.
      Changes in plasma Hcy, serum folate, and vitamin B12 concentrations were analyzed
      by paired t tests, and P values < 0.05 were considered significant. RESULTS:
      Eighteen (56.2%) patients had hyperhomocysteinuria. Vitamin B12 and folate levels
      were normal or high in all cases. Two patients were lost due to transplant or
      irregular drugs consumption. Plasma Hcy levels were reduced in all, and reached
      normal values in 50%. A statistically significant differences between first Hcy
      levels with levels after intervention was found (95% CI, 5.1-8.9, P = 0.0001).
      CONCLUSION: Oral folate 10 mg/day in combination with sublingual vitamin B12, 1
      mg/day can be considered as a favorable treatment for hyperhomocysteinemia in
      dialysis patients.

PMID- 27689110
TI  - Effect of angiotensin II type 1 receptor blockade on kidney ischemia/reperfusion;
      a gender-related difference.
AB  - BACKGROUND: Renal ischemia/reperfusion (I/R) injury may be related to activity of
      reninangiotensin system (RAS), which is gender-related. In this study, it was
      attempted to compare the effect of angiotensin II (Ang II) receptor type 1 (AT1R)
      blockade; losartan in I/R injury in male and female rats. MATERIALS AND METHODS:
      Male and female Wistar rats were assigned as sham surgery, control I/R groups
      treated with vehicle, and case I/R groups treated with losartan (30 mg/kg).
      Vehicle and losartan were given 2 hours before bilateral kidney ischemia induced
      by clamping renal arteries for 45 minutes followed by 24 hours of renal
      reperfusion. RESULTS: The I/R injury significantly increased the serum levels of
      blood urea nitrogen (BUN) and creatinine (Cr), and kidney tissue damage score in
      both genders. However, losartan decreased these values in female rats
      significantly (P < 0.05). This was not observed in male rats. CONCLUSION:
      Losartan protects the kidney from I/R injury in female but not in male rats
      possibly because of gender-related difference of RAS.

PMID- 27689111
TI  - Comparing between results and complications of doing voiding cystourethrogram in
      the first week following urinary tract infection and in 2-6 weeks after urinary
      tract infection in children referring to a teaching hospital.
AB  - INTRODUCTION: Urinary tract infection is the most common genitourinary disease in
      children so about 40% of the children with urinary tract infection suffering from
      reflux that caused some consequences such as pyelonephritis and kidney
      parenchymal injury. OBJECTIVES: This research was conducted to compare the timing
      of voiding cystourethrogram (VCUG) in children with urinary tract infection in
      first week and after the first week of urinary tract infection. PATIENTS AND
      METHODS: This research is a case-control study that both case and control groups
      include 208 children from 1 month to 12 years old with the complain of urinary
      tract infection. In case group, the VCUG was performed at the first week of
      infection and in control group, the VCUG was performed after the first week of
      infection. RESULTS: complication such as dysuria was observed in two-thirds of
      children who VCUG was performed during first week after urinary tract infection.
      Parents stress in case group was more than the other (P=0.015). For overall, the
      incidence of reflux in case and control groups was 49.5% and 50%, respectively.
      The mean of reflux grading in right kidney in case group was lower than control
      group resulting in significant differences between two groups. CONCLUSION:
      According to higher grade of stress in parents and complications due to VCUG at
      the first week of urinary tract infection, it is suggested that VCUG be conducted
      on selective patients in the hospital at the first week of urinary tract
      infection and during hospitalization.

PMID- 27689112
TI  - Comparison of oral Lactobacillus and Streptococcus mutans between diabetic
      dialysis patients with non-diabetic dialysis patients and healthy people.
AB  - INTRODUCTION: Diabetes is associated with higher rates of caries, on the other
      hand some studies have shown that renal failure can be protective against dental
      caries. OBJECTIVES: In this study we compared oral Lactobacillus and
      Streptococcus mutans between diabetic dialysis and non-diabetic dialysis patients
      and the normal population. PATIENTS AND METHODS: During November 2014 to January
      2014, 85 people that referred to our medical care center entered the study. The
      sample included 30 diabetic dialysis, 28 non-diabetic dialysis patients and 27
      healthy people. Oral saliva samples were obtained from their tongue and oral
      floor for microbiological examination. Patients' data were compared before and
      after dialysis. RESULTS: The amount of Lactobacillus and S. mutans did not show a
      significant difference between the three groups (P=0.092 and P=0.966 for S.
      mutans and lactobacillus, respectively). A positive and meaningful correlation
      was seen between fasting blood sugar (FBS) levels and the amount of S. mutans in
      the diabetic dialysis group (P=0.023; r=0.413). A meaningful and positive
      correlation was also seen between the amount of blood urea nitrogen (BUN) after
      dialysis and the amount of oral S. mutans in the non-diabetic dialysis group
      (P=0.03; r=0.403). CONCLUSION: Despite the differences in the prevalence of
      caries that have been reported between renal failure patients and diabetic
      patients, we did not find any significant difference between diabetic dialysis,
      non-diabetic dialysis patients and the healthy population, regarding their amount
      of oral cariogenic bacteria.

PMID- 27689113
TI  - The effects of different electrolyte composition in dialysate on QTc interval; a
      controlled trial.
AB  - INTRODUCTION: Hemodialysis (HD) has impact on the cardiovascular system by
      inducing changes in the characteristics of body fluids such as PH, temperature
      and electrolyte concentrations. In the previous studies, prolongation of the QT
      interval and increase of QT dispersion have been reported during HD sessions.
      These changes were more significant while using solutions with less potassium and
      higher bicarbonate during dialysis. OBJECTIVES: The aim of our study was to
      investigate the effects of different potassium and bicarbonate concentrations on
      electrocardiography (ECG) parameters and the electrochemical balance of cell
      membranes. PATIENTS AND METHODS: This is a double blind controlled clinical trial
      with crossover design. This interventional study has been conducted on 36
      patients over 18 years who undergoing HD 3 times a week for at least 6 months.
      Twelve-lead ECG has been obtained before starting and one hour after end of each
      HD session. The QTc was measured and changes recorded by a cardiologist.
      Correlations were evaluated by univariate regression analysis. RESULTS: 54.38
      years (16 to 77 years), 66.7% were male. No significant increase in QT interval
      has been seen while dialyzing with 2 meq/l potassium and 24 meq/l bicarbonate, 2
      meq/l potassium and 28 meq/l bicarbonate and 3 meq/l potassium and 24 meq/l
      bicarbonate beside high calcium (2.5 meq/l) dialysate was conducted. Age, gender,
      serum calcium and serum bicarbonate level before HD session did not influence the
      mean QT intervals before and after dialysis. CONCLUSION: Concentration of
      potassium beside moderate dose of bicarbonate in dialysis bath had not any
      significant influence on QT intervals after dialysis.

PMID- 27689114
TI  - Correlation between cystatin C-based formulas, Schwartz formula and urinary
      creatinine clearance for glomerular filtration rate estimation in children with
      kidney disease.
AB  - INTRODUCTION: Assessment of glomerular filtration rate (GFR) is an important tool
      for monitoring renal function. OBJECTIVES: Regarding to limitations in available
      methods, we intended to calculate GFR by cystatin C (Cys C) based formulas and
      determine correlation rate of them with current methods. PATIENTS AND METHODS: We
      studied 72 children (38 boys and 34 girls) with renal disorders. The 24 hour
      urinary creatinine (Cr) clearance was the gold standard method. GFR was measured
      with Schwartz formula and Cys C-based formulas (Grubb, Hoek, Larsson and Simple).
      Then correlation rates of these formulas were determined. RESULTS: Using Pearson
      correlation coefficient, a significant positive correlation between all formulas
      and the standard method was seen (R(2) for Schwartz, Hoek, Larsson, Grubb and
      Simple formula was 0.639, 0.722, 0.705, 0.712, 0.722, respectively) (P<0.001).
      Cys C-based formulas could predict the variance of standard method results with
      high power. These formulas had correlation with Schwarz formula by R(2) 0.62-0.65
      (intermediate correlation). Using linear regression and constant (y-intercept),
      it revealed that Larsson, Hoek and Grubb formulas can estimate GFR amounts with
      no statistical difference compared with standard method; but Schwartz and Simple
      formulas overestimate GFR. CONCLUSION: This study shows that Cys C-based formulas
      have strong relationship with 24 hour urinary Cr clearance. Hence, they can
      determine GFR in children with kidney injury, easier and with enough accuracy. It
      helps the physician to diagnosis of renal disease in early stages and improves
      the prognosis.

PMID- 27689115
TI  - The effect of lactulose supplementation on fecal microflora of patients with
      chronic kidney disease; a randomized clinical trial.
AB  - INTRODUCTION: Lactulose is a prebiotic with bifidogenic and urea reduction
      effects. It can improve Bifidobacteria and Lactobacilli counts in healthy humans
      and it may possibly have similar effects in chronic kidney disease (CKD)
      patients. OBJECTIVES: To investigate the effect of lactulose on fecal microflora
      of patients with CKD. PATIENTS AND METHODS: Thirty-two patients with stages 3 and
      4 of CKD (43.8% male with mean age of 58.09+/-12.75 years) were randomly assigned
      to intervention (n=16) and control (n=16) groups. Patients in intervention group
      received 30 mm lactulose syrup three times a day for an 8-week period. Control
      group received placebo 30 mm three times a day. A fecal sample was obtained from
      all patients at the beginning and at the end of the study and Bifidobacteria and
      Lactobacilli was counted. RESULTS: Creatinine (Cr) significantly decreased in
      intervention group (3.90+/-1.43 to 3.60+/-1.44, P=0.003) and increased in control
      group (3.87+/-2.08 to 4.11+/-1.99, P=0.03). Although Bifidobacterial and
      Lactobacilli counts were similar before intervention, they were significantly
      higher at the end of the study in lactulose group (P=0.01 and P=0.04,
      respectively). Lactulose led to significant increase in fecal Bifidobacterial
      counts (3.61+/-0.54 to 4.90+/-0.96, P<0.001) and Lactobacilli counts (2.79+/-1.00
      to 3.87+/-1.13, P<0.001), while the change in placebo group was not significant.
      CONCLUSION: Lactulose administration will increase Bifidobacteria and
      Lactobacillus counts in patients with CKD.

PMID- 27689117
TI  - Hypertension in children in emergency department.

PMID- 27689116
TI  - Splenic abscess due to fungal infection after kidney transplantation; a case
      report.
AB  - Splenic abscess is one of the rare and potentially life-threatening complications
      after kidney transplantation. Splenic abscess generally occurs in patients who
      have immunodeficiency state. It becomes more important with the increased use of
      immunosuppressed drugs and organ transplantation. The clinical presentation of
      splenic abscess is insidious, often with constitutional symptoms. Left upper
      quadrant tenderness is an uncommon sign. Therefore, its diagnosis is difficult
      and requires a high degree of clinical suspicion. We report a case under renal
      transplantation with recurrent fungal infection in different organs with two
      episodes of fungemia who died after splenectomy. 

PMID- 27689118
TI  - Association of bone mineral density with biochemical markers of bone turnover in
      hemodialysis children.
AB  - INTRODUCTION: Although some descriptive and cross-sectional studies have been
      reported about bone mass in chronic kidney disease (CKD) children, only a few
      studies investigated markers of bone turnover and the bone mass measurements.
      OBJECTIVES: The aim of this study was to evaluate the association between bone
      mineral density (BMD) and biochemical markers of bone turnover in hemodialysis
      (HD) children. PATIENTS AND METHODS: The children who had received dialysis for
      at least the preceding 6-month were included. BMD was measured for total body,
      the lumbar spine and the femoral neck and the blood samples were tested to assess
      biochemical bone turnover markers. RESULTS: The study group was comprised of 27
      patients with CKD, 9 males (33%) and 18 females (67%) with the mean+/-SD age of
      the subjects 14.9+/-4.5 years. Positive significant correlations of parathyroid
      hormone (PTH) with total body bone densitometry Z-score, lumbar spine and femoral
      neck Z-score(r=0.43, P=0.06; r=0.41, P=0.08 and r=0.45, P=0.05, respectively) was
      noted. In addition, positive significant correlations calcium and total body,
      lumbar spine and femoral neck Z-score (r=0.52, P=0.02; r=0.28, P=0.23 and r=0.36,
      P=0.12, respectively) was seen. Interestingly, a positive significant correlation
      between alkaline phosphatase (ALP) and lumbar spine Z-score was found (r=0.46,
      P=0.04), while the correlation of this parameter with total body and femoral neck
      Z-score was not significant (P>0.05). CONCLUSION: In our study, majority of
      patients with CKD had low level of BMD. In addition, lower levels of calcium
      (Ca), phosphorus (P), PTH and 25 (OH) vitamins D in patients with abnormal BMD Z
      scores were detected.

PMID- 27689119
TI  - Effect of selenium supplementation on lipid profile in hemodialysis patients.
AB  - INTRODUCTION: One of the major causes of mortality in chronic kidney disease
      (CKD) patients on hemodialysis is premature atherosclerosis. Selenium, a trace
      element involved in important enzymatic activities inside the body, has
      protective effects against lipid oxidation and inhibits cholesterol accumulation
      in blood vessels. OBJECTIVES: To determine the effect of selenium supplementation
      on lipid profile in hemodialysis patients. PATIENTS AND METHODS: In this double
      blinded randomized clinical trial which lasted for 3 months, 84 hemodialysis
      patients with selenium deficiency were divided into experimental group (received
      selenium supplementation) or control group (received placebo). Total cholesterol,
      low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), blood urea
      nitrogen (BUN), creatinine, and selenium level were measured before and after the
      study. RESULTS: Mean (+/-SD) serum LDL-C level significantly increased in
      experimental group from 85.66 (+/-31.12) to 109.12 (+/-32.29) mg/dl (P<0.001).
      Likewise, in control group serum LDL-C significantly increased from 80.55 (+/
      21.13) to 97.05 (+/-28.07) mg/dl (P<0.001). However, with control of LDL-C effect
      before and after the study, it was revealed that LDL-C change was not
      statistically significant (P=0.21). Similarly, total cholesterol and triglyceride
      levels did not show significant changes before and after the study in any group.
      CONCLUSION: Selenium supplementation had no beneficial effect on lipid profile in
      hemodialysis patients.

PMID- 27689120
TI  - Effect of aerobic exercise against vanadyl sulphate-induced nephrotoxicity and
      hepatotoxicity in rats.
AB  - INTRODUCTION: Vanadium compounds are insulin like drugs which are accompanied
      with nephrotoxicity and hepatotoxicity as their major side effects. Aerobic
      exercise is well known as an approach to reduce the side effects of many drugs.
      OBJECTIVES: This study was designed to determine the role of aerobic exercise
      against vanadyl sulphate induced nephrotoxicity and hepatotoxicity in male rats.
      MATERIALS AND METHODS: Twenty-four male Wistar rats were randomly divided into
      three groups. Group I had aerobic exercise on a treadmill 5 days/week for 6
      weeks. Group II received vanadyl sulphate (50 mg/kg/week; i.p.) for 6 weeks.
      Group III had combination of exercise and vanadyl sulphate therapy as groups 1
      and 2. At the end of study, blood samples were obtained, and the animals were
      sacrificed for the tissues injury determination. RESULTS: Vanadyl sulphate alone
      increased serum levels of blood urea nitrogen (BUN), creatinine (Cr), and kidney
      weight (KW) and kidney tissue damage score (KTDS) (P<0.05). These observations
      revealed nephrotoxicity induced by vanadyl sulphate, although exercise training
      did not attenuate these results. In addition, vanadyl sulphate alone induced
      liver tissue damage score and exercise training intensified it insignificantly,
      while the serum levels of aspartate amino transferase and alanine amino
      transferase were greater in exercise alone group than others groups. CONCLUSION:
      Aerobic exercise could not attenuate vanadyl sulphate induced nephrotoxicity and
      hepatotoxicity. These findings must be considered when vanadyl sulphate is
      suggested as insulin like drug.

PMID- 27689121
TI  - Gamma-aminobutyric acid aggravates nephrotoxicity induced by cisplatin in female
      rats.
AB  - INTRODUCTION: Cisplatin (CP) is a major antineoplastic drug for treatment of
      solid tumors. CP-induced nephrotoxicity may be gender-related. This is while
      gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central
      nervous system that has renoprotective impacts on acute renal injury. OBJECTIVES:
      This study was designed to investigate the protective role of GABA against CP
      induced nephrotoxicity in male and female rats. MATERIALS AND METHODS: Sixty
      Wistar male and female rats were used in eight experimental groups. Both genders
      received GABA (50 MUg/kg/day; i. p.) for 14 days and CP (2.5 mg/kg/day; i. p.)
      was added from day 8 to the end of the study, and they were compared with the
      control groups. At the end of the study, all animals were sacrificed and the
      serum levels of blood urea nitrogen (BUN), creatinine (Cr), nitrite,
      malondialdehyde (MDA), and magnesium (Mg) were measured. The kidney tissue damage
      was also determined via staining. RESULTS: CP significantly increased the serum
      levels of Cr and BUN, kidney weight, and kidney tissue damage score in both
      genders (P<0.05). GABA did not attenuate these markers in males; even these
      biomarkers were intensified in females. Serum level of Mg, and testis and uterus
      weights did not alter in the groups. However, the groups were significantly
      different in terms of nitrite and MDA levels. CONCLUSION: It seems that GABA did
      not improve nephrotoxicity induced by CP-treated rats, and it exacerbated renal
      damage in female rats.

PMID- 27689122
TI  - Attention-deficit/hyperactivity disorder in children with overactive bladder; a
      case-control study.
AB  - INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is the most common
      childhood psychiatric disorder. This disorder is more prevalent in some chronic
      diseases. OBJECTIVES: To investigate ADHD in children with overactive bladder.
      PATIENTS AND METHODS: A number of 92 children with overactive bladder and 92
      healthy children without overactive bladder (age range of both groups 5 to 12
      years old) were included in this study as case and control groups, respectively.
      Participants were selected from children who had referred to a pediatric clinic
      in Arak city, Iran. ADHD types (inattentive, hyperactive-impulsive, and mixed)
      were diagnosed by Conner's Parent Rating Scale and Diagnostic and Statistical
      Manual of Mental Disorders IV-TR (DSM-IV-TR) criteria. Data were analyzed by chi
      square and t tests. RESULTS: In both groups, 51 children (27.7%) had ADHD. The
      prevalence of ADHD in the case group (33 cases, 35.9%) was significantly higher
      than the control group (18 cases, 19.6%) (P = 0.021). Inattentive ADHD was
      observed in 22 participants (23.9%) of the case group and nine participants of
      the control group (9.7%) (P = 0.047). Despite this significant difference, three
      (3.2%) and four (4.3%) children were affected by hyperactive-impulsive ADHD (P =
      0.73), and eight (8.6%) and five (5.4%) children were affected by mixed ADHD (P =
      0.42) in the case and control groups, respectively. CONCLUSION: ADHD bladder is
      significantly more common in children with overactive bladder than healthy
      children. The observed correlation between ADHD and overactive bladder makes
      psychological counseling mandatory in children with overactive bladder.

PMID- 27689124
TI  - Acute kidney injury in patients with paraquat intoxication; a case report and
      review of the literature.
AB  - Paraquat and diquat are classified as bipyridyl compounds not only leads to acute
      organ damage, but also to a variety of complications. Patients with severe
      paraquat-induced poisoning may succumb to multiple organ failure involving the
      circulatory and respiratory systems. Deliberate self-poisoning with paraquat
      continues to be a major public health concern in many developing countries. At
      present there is no specific antidote to paraquat poisoning, hence the need to
      more focus on prevention and in cases of poisoning aggressive decontamination to
      prevent further absorption. This article presented a 12-year-old male with acute
      kidney injury following the ingestion of paraquat in suicidal attempt and serves
      to explore the complications associated with paraquat poisoning and current
      recommended treatment. 

PMID- 27689123
TI  - Cross-fused renal ectopia associated with vesicoureteral reflux; a case report.
AB  - Crossed renal ectopia is a rare urinary system anomaly which mostly is
      asymptomatic and is diagnosed incidentally. Urinary obstruction, infection, and
      neoplasia of the urinary system and nephrolithiasis are main complications of
      this anomaly. A 6-year-old boy admitted to the hospital with colicky abdominal
      pain and nausea. Abdominal examination revealed tenderness in right lower
      quadrant. Urine analysis and culture were normal. Kidney ultrasonography showed
      right kidney in pelvis cavity with no kidney tissue in left side. TC 99-DMSA scan
      demonstrated no radiotracer accumulation in the normal renal area. Radiotracer
      accumulation was seen in the pelvis area with a deviation to the left. Voiding
      cystoureterogram revealed right sided grade II vesicoureteral reflux. Severe
      urological anomalies in children may be asymptomatic or have nonspecific symptoms
      such as abdominal pain. 

PMID- 27689125
TI  - Paraneoplastic proteinuria in papillary renal cell carcinoma; a case report.
AB  - We report a 55-year-old man presented with anemia and weakness, history of flank
      pain, hematuria and nephrotic syndrome. Spiral abdominopelvic computerized
      tomography (CT) scan showed multiloculated cystic mass (120 *100 *80 mm) in lower
      portion of left kidney with internal enhancing solid components and coarse
      peripheral calcifications. Radical nephrectomy of left kidney was done and biopsy
      confirmed renal cell carcinoma (RCC), papillary type, sarcomatoid foci, Fuhrman
      grade III. We assumed that, presence of nephrotic syndrome and paraneoplastic
      glomerulopathy leaded to heavy proteinuria in this case. Secondary,
      paraneoplastic glomerulopathy such as immunoglobulin A nephropathy and focal
      segmental glomerulosclerosis as a paraneoplastic syndrome of RCC have been
      reported previously. RCC can present with a wide range of signs and symptoms.
      Atypical presentations of papillary RCC such as proteinuria should be considered
      for patients presenting with nephrotic syndrome. 

PMID- 27689126
TI  - Principal component analysis (PCA) of volatile terpene compounds dataset emitted
      by genetically modified sweet orange fruits and juices in which a D-limonene
      synthase was either up- or down-regulated vs. empty vector controls.
AB  - We have categorized the dataset from content and emission of terpene volatiles of
      peel and juice in both Navelina and Pineapple sweet orange cultivars in which D
      limonene was either up- (S), down-regulated (AS) or non-altered (EV; control)
      ("Impact of D-limonene synthase up- or down-regulation on sweet orange fruit and
      juice odor perception"(A. Rodriguez, J.E. Peris, A. Redondo, T. Shimada, E.
      Costell, I. Carbonell, C. Rojas, L. Pena, (2016)) [1]). Data from volatile
      identification and quantification by HS-SPME and GC-MS were classified by
      Principal Component Analysis (PCA) individually or as chemical groups. AS juice
      was characterized by the higher influence of the oxygen fraction, and S juice by
      the major influence of ethyl esters. S juices emitted less linalool compared to
      AS and EV juices. 

PMID- 27689127
TI  - Data on the histological and immune cell response in the popliteal lymph node in
      mice following exposure to metal particles and ions.
AB  - Hip implants containing cobalt-chromium (CoCr) have been used for over 80 years.
      In patients with metal-on-metal (MoM) hip implants, it has been suggested that
      wear debris particles may contribute to metal sensitization in some individuals,
      leading to adverse reactions. This article presents data from a study in which
      the popliteal lymph node assay (PLNA) was used to assess immune responses in mice
      treated with chromium-oxide (Cr2O3) particles, metal salts (CoCl2, CrCl3, and
      NiCl2) or Cr2O3 particles with metal salts ("A preliminary evaluation of immune
      stimulation following exposure to metal particles and ions using the mouse
      popliteal lymph node assay" (B.E. Tvermoes, K.M. Unice, B. Winans, M. Kovochich,
      E.S. Fung, W.V. Christian, E. Donovan, B.L. Finley, B.L. Kimber, I. Kimber, D.J.
      Paustenbach, 2016) [1]). Data are presented on (1) the chemical characterization
      of TiO2 particles (used as a particle control), (2) clinical observations in mice
      treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts,
      (3) PLN weight and weight index (WI) in mice treated with Cr2O3 particles, metal
      salts or Cr2O3 particles with metal salts, (4) histological changes in PLNs of
      mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal
      salts, (5) percentages of immune cells in the PLNs of mice treated with Cr2O3
      particles, metal salts or Cr2O3 particles with metal salts, and (6) percentages
      of proliferating cells in the PLNs of mice treated with Cr2O3 particles, metal
      salts or Cr2O3 particles with metal salts. 

PMID- 27689128
TI  - Data on recovery of 21 amino acids, 9 biogenic amines and ammonium ions after
      spiking four different beers with five concentrations of these analytes.
AB  - A novel chromatographic method for the simultaneous analysis of nine biogenic
      amines, 21 amino acids and ammonium ions in beer has been recently described in
      "A UHPLC method for the simultaneous analysis of biogenic amines, amino acids and
      ammonium ions in beer" (Redruello et al., 2017) [1]. The present article provides
      recovery data of the 31 analytes after spiking four different beers with five
      concentrations of each analyte (15, 30, 60, 120 and 240 uM). 

PMID- 27689129
TI  - Data on the application of Functional Data Analysis in food fermentations.
AB  - This article refers to the paper "Assessment of table olive fermentation by
      functional data analysis" (Ruiz-Bellido et al., 2016) [1]. The dataset include
      pH, titratable acidity, yeast count and area values obtained during fermentation
      process (380 days) of Alorena de Malaga olives subjected to five different
      fermentation systems: i) control of acidified cured olives, ii) highly acidified
      cured olives, iii) intermediate acidified cured olives, iv) control of
      traditional cracked olives, and v) traditional olives cracked after 72 h of
      exposure to air. Many of the Tables and Figures shown in this paper were deduced
      after application of Functional Data Analysis to raw data using a routine
      executed under R software for comparison among treatments by the transformation
      of raw data into smooth curves and the application of a new battery of
      statistical tools (functional pointwise estimation of the averages and standard
      deviations, maximum, minimum, first and second derivatives, functional
      regression, and functional F and t-tests). 

PMID- 27689130
TI  - Retracted: Flavonoid-Deficient Mutants in Grass Pea (Lathyrus sativus L.):
      Genetic Control, Linkage Relationships, and Mapping with Aconitase and S
      Nitrosoglutathione Reductase Isozyme Loci.
AB  - [This retracts the article DOI: 10.1100/2012/345983.].

PMID- 27689131
TI  - Reactive-Diffusive-Advective Traveling Waves in a Family of Degenerate Nonlinear
      Equations.
AB  - This paper deals with the analysis of existence of traveling wave solutions (TWS)
      for a diffusion-degenerate (at D(0) = 0) and advection-degenerate (at h'(0) = 0)
      reaction-diffusion-advection (RDA) equation. Diffusion is a strictly increasing
      function and the reaction term generalizes the kinetic part of the Fisher-KPP
      equation. We consider different forms of the convection term h(u): (1)  h'(u) is
      constant k, (2)  h'(u) = ku with k > 0, and (3) it is a quite general form which
      guarantees the degeneracy in the advective term. In Case 1, we prove that the
      task can be reduced to that for the corresponding equation, where k = 0, and then
      previous results reported from the authors can be extended. For the other two
      cases, we use both analytical and numerical tools. The analysis we carried out is
      based on the restatement of searching TWS for the full RDA equation into a two
      dimensional dynamical problem. This consists of searching for the conditions on
      the parameter values for which there exist heteroclinic trajectories of the
      ordinary differential equations (ODE) system in the traveling wave coordinates.
      Throughout the paper we obtain the dynamics by using tools coming from
      qualitative theory of ODE.

PMID- 27689132
TI  - Insulin-Like Growth Factor-1 and Selected Insulin-Like Growth Factor Binding
      Protein Concentrations during an Ultramarathon Sled Dog Race.
AB  - The objective of this study was to investigate the effects of running a 1000-mile
      (1600 km) endurance sled dog race on serum insulin-like growth factor-1 (IGF-1)
      and insulin-like growth factor binding proteins 1 and 3 (IGFBP-1 and IGFBP-3).
      Serum was examined from 12 sled dogs prior to the race, at midrace (approximately
      690 km), and again at the finish. IGF-1, IGFBP-1, and IGFBP-3 were assessed using
      radioimmunoassay or enzyme linked immune-absorbance assays. Mean prerace
      concentrations were significantly higher than midrace and end-race concentrations
      at 215.93 +/- 80.51 ng/mL, 54.29 +/- 25.45 ng/mL, and 55.53 +/- 28.25 ng/mL,
      respectively (P < 0.001). Mean IGFBP-1 concentrations were not different across
      these time periods at 24.1 +/- 15.8 ng/mL, 25.7 +/- 14.0 ng/mL, and 26.6 +/- 17.6
      ng/mL, respectively. IGFBP-3 concentrations showed a modest significant decrease
      across time periods at 3,067 +/- 2,792 ng/mL, 2,626 +/- 2,310 ng/mL, and 2,331 +/
      2,301 ng/mL, respectively (P < 0.01). Endurance sled dogs show a precipitous
      drop in serum IGF-1 concentrations. These differences may be related to fuel
      utilization and excessive negative energy balance associated with the loss of
      body condition during racing. The relative stability of IGFBP-1 and IGFBP-3
      suggests that IGF-1 anabolic signaling is diminished during ultramarathon racing.
      Further studies comparing the influence of time and duration of exercise versus
      negative energy balance on serum IGF-1 status are warranted to better understand
      exercise versus negative energy balance differences.

PMID- 27689133
TI  - Fuzzy Logic for Incidence Geometry.
AB  - The paper presents a mathematical framework for approximate geometric reasoning
      with extended objects in the context of Geography, in which all entities and
      their relationships are described by human language. These entities could be
      labelled by commonly used names of landmarks, water areas, and so forth. Unlike
      single points that are given in Cartesian coordinates, these geographic entities
      are extended in space and often loosely defined, but people easily perform
      spatial reasoning with extended geographic objects "as if they were points."
      Unfortunately, up to date, geographic information systems (GIS) miss the
      capability of geometric reasoning with extended objects. The aim of the paper is
      to present a mathematical apparatus for approximate geometric reasoning with
      extended objects that is usable in GIS. In the paper we discuss the fuzzy logic
      (Aliev and Tserkovny, 2011) as a reasoning system for geometry of extended
      objects, as well as a basis for fuzzification of the axioms of incidence
      geometry. The same fuzzy logic was used for fuzzification of Euclid's first
      postulate. Fuzzy equivalence relation "extended lines sameness" is introduced.
      For its approximation we also utilize a fuzzy conditional inference, which is
      based on proposed fuzzy "degree of indiscernibility" and "discernibility measure"
      of extended points.

PMID- 27689134
TI  - The Relationship between Body Mass Index and Depression among High School Girls
      in Ahvaz.
AB  - Objective. Today, obesity and depression are two major illnesses that are on the
      rise all over the world and threaten human health. This research was done to
      determine the relationship between Body Mass Index (BMI) and depression among
      Ahvaz high school female students. Method. In a descriptive-analytical study
      using stratified random sampling, 400 female high school students in academic
      year of 2013-2014 were picked and their height and weight were measured. BMI was
      classified based on World Health Organization classification. To assess the
      severity of depression, Beck depression questionnaire was used. In order to
      analyze the data, descriptive statistics and Pearson correlation test were used.
      Results. In terms of BMI 9% of students were slim, 77% were at an acceptable
      level, and 14% were overweight. Also, the prevalence of depression was 86.20%
      major depression and 13.79% moderate depression for obese persons, 10.41% major
      depression and 70.83% moderate depression for overweight persons, 8.78% major
      depression and 12.97% moderate depression for normal weight persons, and 9%
      moderate depression for slim persons. The relationship between BMI and depression
      among high school students is positive and significant (P < 0.001; r = 0.555).
      Conclusion. There is a positive and significant relationship between BMI and the
      severity of depression among Ahvaz high school female students. 

PMID- 27689135
TI  - Topical Colchicine Gel versus Diclofenac Sodium Gel for the Treatment of Actinic
      Keratoses: A Randomized, Double-Blind Study.
AB  - Introduction. Actinic keratoses (AKs), a premalignant skin lesion, are a common
      lesion in fair skin. Although destructive treatment remains the gold standard for
      AKs, medical therapies may be preferable due to the comfort and reliability .This
      study aims to compare the effects of topical 1% colchicine gel and 3% diclofenac
      sodium gel in AKs. Materials and Methods. In this randomized double-blind study,
      70 lesions were selected. Patients were randomized before receiving either 1%
      colchicine gel or 3% diclofenac sodium cream twice a day for 6 weeks. Patients
      were evaluated in terms of their lesion size, treatment complications, and
      recurrence at 7, 30, 60, and 120 days after treatment. Results. The mean of
      changes in the size was significant in both groups both before and after
      treatment (<0.001). The mean lesion size before treatment and at 30, 60, and 120
      days was not different between the two groups (p > 0.05). No case of erythema was
      seen in the colchicine group, while erythema was seen in 22.9% (eight cases) of
      patients in the diclofenac sodium group (p = 0.005). Conclusions. 1% colchicine
      gel was a safe and effective medication with fewer side effects and lack of
      recurrence of the lesion. 

PMID- 27689137
TI  - In utero Diagnosis of Long QT Syndrome: Challenges, Progress, and the Future.

PMID- 27689136
TI  - Endothelial Cellular Responses to Biodegradable Metal Zinc.
AB  - Biodegradable zinc (Zn) metals, a new generation of biomaterials, have attracted
      much attention due to their excellent biodegradability, bioabsorbability, and
      adaptability to tissue regeneration. Compared with magnesium (Mg) and iron (Fe),
      Zn exhibits better corrosion and mechanical behaviors in orthopedic and stent
      applications. After implantation, Zn containing material will slowly degrade, and
      Zn ions (Zn2+) will be released to the surrounding tissue. For stent
      applications, the local Zn2+concentration near endothelial tissue/cells could be
      high. However, it is unclear how endothelia will respond to such high
      concentrations of Zn2+, which is pivotal to vascular remodeling and regeneration.
      Here, we evaluated the short-term cellular behaviors of primary human coronary
      artery endothelial cells (HCECs) exposed to a concentration gradient (0-140 MUM)
      of extracellular Zn2+. Zn2+ had an interesting biphasic effect on cell viability,
      proliferation, spreading, and migration. Generally, low concentrations of Zn2+
      promoted viability, proliferation, adhesion, and migration, while high
      concentrations of Zn2+ had opposite effects. For gene expression profiles, the
      most affected functional genes were related to cell adhesion, cell injury, cell
      growth, angiogenesis, inflammation, vessel tone, and coagulation. These results
      provide helpful information and guidance for Zn-based alloy design as well as the
      controlled release of Zn2+in stent and other related medical applications.

PMID- 27689138
TI  - Characteristics of Cannabis-Only and Other Drug Users Who Visit the Emergency
      Department.
AB  - Emergency department (ED) settings have gained interest as venues for illegal
      drug misuse prevention and intervention, with researchers and practitioners
      attempting to capitalize on the intersection of need and opportunity within these
      settings. This study of 686 adult patients visiting two EDs for various reasons
      who admitted drug use compared daily cannabis-only users, nondaily cannabis-only
      users, and other drug users on sociodemographic and drug-related severity
      outcomes. The three drug use groups did not differ on most sociodemographic
      factors or medical problem severity scores. Forty-five percent of the sample was
      identified as having a drug use problem. ED patients who used drugs other than
      cannabis were at particular risk for high drug use severity indicators and
      concomitant problems such as psychiatric problems and alcohol use severity.
      However, 19-29% of cannabis-only users were identified as having problematic drug
      use. Furthermore, daily cannabis-only users fared less well than nondaily
      cannabis users with regard to drug use severity indicators and self-efficacy for
      avoiding drug use. Results may assist emergency medicine providers and medical
      social workers in matching patients to appropriate intervention. For example,
      users of drugs other than cannabis (and perhaps heavy, daily cannabis-only users)
      may need referral to specialty services for further assessment. Enhancement of
      motivation and self-efficacy beliefs could be an important target of prevention
      and treatment for cannabis-only users screened in the ED.

PMID- 27689139
TI  - Determinants of and Barriers to Hormonal and Surgical Treatment Receipt Among
      Transgender People.
AB  - Purpose: Medical gender confirmation therapy (GCT) plays an important role in
      transgender health; however, its prevalence and determinants constitute an area
      of uncertainty. Methods: Data for this cross-sectional study were obtained from
      an online survey distributed from October 2012 through the end of 2013 among
      persons who visited the social media sites of a transgender education and social
      networking meeting. Eligible respondents (n=280) were persons whose gender
      identity was different from their sex assigned at birth and who responded to
      questions about previously received or planned hormonal therapy (HT), chest
      reconstruction, or genital surgery. Multivariable logistic regression models
      examined how receipt and plans to receive different GCT types were associated
      with participants' characteristics and gender identity. Results: The respective
      percentages of ever and current HT were 58% and 47% for transwomen and 63% and
      57% for transmen. Genital surgery was reported by 11 participants; all
      transwomen. Relative to transmen, transwomen were thrice more likely to report
      plans to undergo genital surgery. By contrast, transmen were more than 10 times
      as likely as transwomen to have had or planned chest surgery. Older participants
      and those who were in a committed relationship were less likely to plan future
      GCT. Having health insurance was not associated with GCT receipt. Treatment cost
      was named as the main problem by 23% of transwomen and 29% of transmen. Accessing
      a qualified healthcare provider for transgender-related care was listed as the
      primary reason for not receiving surgery by 41% of transmen and 2% of transwomen.
      Conclusions: Prevalence of GCT differed across subgroups of participants and was
      lower than corresponding estimates reported elsewhere. The variability of results
      may reflect differences in recruitment procedures and response rates; however, it
      is also possible that it may be driven by geographic, socioeconomic, and health
      related heterogeneity of the transgender population.

PMID- 27689140
TI  - Flexible growing rods: a biomechanical pilot study of polymer rod constructs in
      the stability of skeletally immature spines.
AB  - BACKGROUND: Surgical treatments for early onset scoliosis (EOS) correct
      curvatures and improve respiratory function but involve many complications. A
      distractible, or 'growing rod,' implant construct that is more flexible than
      current metal rod systems may sufficiently correct curves in small children and
      reduce complications due to biomechanical factors. The purpose of this pilot
      study was to determine ranges of motion (ROM) after implantation of simulated
      growing rod constructs with a range of clinically relevant structural properties.
      The hypothesis was that ROM of spines instrumented with polymer rods would be
      greater than conventional metal rods and lower than non-instrumented controls.
      METHODS: Biomechanical tests were conducted on six thoracic spines from
      skeletally immature domestic swines (35-40 kg). Paired pedicle screws were used
      as anchors at proximal and distal levels. Specimens were tested under the
      following conditions: control, then dual rods of polyetheretherketone (PEEK)
      (diameter 6.25 mm), titanium (4 mm), and cobalt-chrome alloy (CoCr) (5 mm).
      Lateral bending (LB) and flexion-extension (FE) moments were applied, and
      vertebral rotations were measured. Differences were determined by two-tailed t
      tests and Bonferroni for four primary comparisons: PEEK vs control and PEEK vs
      CoCr, in LB and FE (alpha = 0.05/4). RESULTS: In LB, ROM of spine segments after
      instrumenting with PEEK rods was lower than the non-instrumented control
      condition at each instrumented level. ROM was greater with PEEK rods than with Ti
      and CoCr rods at every instrumented level. Combining treated levels, in LB, ROM
      for PEEK rods was 35 % of control (p < 0.0001) and 270 % of CoCr rods (p < 0.01).
      In FE, ROM with PEEK was 27 % of control (p < 0.001) and 180 % of CoCr (p <
      0.01). At proximal and distal adjacent non-instrumented levels in FE, mean ROM
      was lower for PEEK than for either metal. CONCLUSIONS: PEEK rods increased
      flexibility versus metal rods, and decreased flexibility versus non-instrumented
      controls, both over the entire instrumented segment and at each individual level.
      Smaller mean increases in ROM at proximal and distal adjacent motion segments
      occurred with PEEK compared to metal rods, which may help decrease complications,
      such as junctional kyphosis. Flexible growing rods may eventually help improve
      treatment options for young patients with severe deformity.

PMID- 27689141
TI  - Adjuvant Aromatase Inhibitors in Early Breast Cancer May Not Increase the Risk of
      Falls.
AB  - BACKGROUND: Falling increases the risk for fracture. The impact of adjuvant
      aromatase inhibitors (AI) on the risk of falls is undefined. METHODS: A
      retrospective case control study was performed examining women with early stage
      breast cancer on adjuvant AI and matched controls without cancer. Fall and
      fracture data were abstracted from the medical record. RESULTS: Matched pairs of
      332 women were identified (total N = 664). There was no statistically significant
      difference in the odds of a fall between cases and controls, p = 0.86. Similarly,
      the odds of a fracture between cases and controls was not significantly
      different, p = 1.0. There were 35 pairs in which the case fractured but the
      control did not and equal number of pairs where the control fractured but the
      case did not. For pairs in which control fractured but case did not, the median
      age at fracture was significant higher than that for pairs in which case
      fractured but the control did not (71 vs. 63 years p = 0.0003). CONCLUSION: This
      study did not identify a difference in the incidence of falls or fractures in
      women on adjuvant AI compared to their age matched controls without breast
      cancer. Prospective studies of falls and fracture in women on adjuvant AI therapy
      compared to age match controls would aid in the identification of fracture risk.

PMID- 27689142
TI  - Editorial.
AB  - I am delighted to introduce you to the very first issue of Ultrasound
      International Open (UIO), a new journal on interdisciplinary ultrasound in
      medicine and biology! 

PMID- 27689143
TI  - Accuracy of Contrast-Enhanced Ultrasound in the Diagnosis of Bile Duct
      Obstruction.
AB  - PURPOSE: To investigate the ability of contrast-enhanced ultrasound (CEUS) to
      differentiate benign from malignant lesions causing biliary duct obstruction.
      MATERIALS AND METHODS: Between November 2006 and December 2013, 59 patients with
      bile duct obstruction of undetermined cause in baseline ultrasound underwent CEUS
      study. The enhancement and posterior washout were analyzed in real time all along
      the study duration (5'). The final diagnosis suggested by CEUS was compared with
      histologic diagnosis (47.5%) or with radiologic follow-up with TC, RM or ERCP.
      RESULTS: Final diagnoses included 42 malignant lesions (cholangiocarcinoma n=22,
      metastases n=6, pancreatic carcinoma n=6, hepatocarcinoma n=4, gallbladder
      carcinoma n=2, ampullary carcinoma n=1 and lymphoma n=1) and 17 benign lesions
      (lithiasis or biliary sludge n=15, xanthogranulomatous cholecystitis n=1 and
      indeterminate n=1). CEUS accuracy compared with final diagnoses based on combined
      reference standard was 86.4%. CEUS correctly identified 36 of 42 malignant
      lesions (sensibility 85.7%) and 15 of 17 benign lesions (specificity 88.2%). The
      positive predictive value of CEUS for malignancy was 94.7%, while the negative
      predictive value was 71.4%. CONCLUSION: CEUS is useful to differentiate between
      benign and malignant causes of obstructive jaundice. This technique improves the
      detection of bile duct invasion in hepatic neoplasms and permits better
      evaluation of intra- and extraductal extension of hilar hepatobiliary tumors.

PMID- 27689144
TI  - Assessment of Ultrasound Features Predicting Axillary Nodal Metastasis in Breast
      Cancer: The Impact of Cortical Thickness.
AB  - PURPOSE: To evaluate the accuracy of axillary ultrasound (AUS) in detecting nodal
      metastasis in patients with early-stage breast cancer and to identify AUS
      features with high predictive power. MATERIALS AND METHODS: Prospective single
      center preliminary study in 105 patients with a primary diagnosis of breast
      cancer and clinically negative axilla. AUS was performed using a 12 MHz linear
      array transducer before ultrasound-guided needle biopsy. Nodal characteristics
      (shape, longitudinal-transverse [LT] axis ratio, margins, cortical thickness,
      hyperechoic hilum) were correlated with histopathological nodal status after SLNB
      or axillary lymph node dissection (ALND). RESULTS: Nodal metastases were present
      in 42/105 patients (40.0%). Univariate analyses showed that absence of
      hyperechoic hilum, round shape, LT axis ratio<2, sharp margins and cortical
      thickness>3 mm were associated with lymph node metastasis. Multivariate logistic
      regression analysis revealed cortical thickness > 3 mm as an independent
      predictive parameter for nodal involvement. Sensitivity, specificity, positive
      predictive value, negative predictive value and accuracy were 66.7, 74.6, 63.6,
      77.0% and 71.4% respectively when cortical thickness > 3 mm was applied as the
      criterion for AUS positivity. Axillary tumor volume was low in patients with
      pT1/2 tumors and negative AUS, since only 3.2% of patients had > 2 metastatic
      lymph nodes. CONCLUSION: Cortical thickness>3 mm is a reliable predictor of nodal
      metastatic involvement. Negative AUS does not exclude lymph node metastases, but
      extensive axillary tumor volume is rare.

PMID- 27689146
TI  - Unusual Hyperechoic Appearance of Hodgkin's Lymphoma in the Liver.

PMID- 27689147
TI  - Contrast-Enhanced Ultrasound of Anaplastic Thyroid Cancer: A Case Report and
      Review of the Literature.

PMID- 27689145
TI  - Evaluation of Acoustic Radiation Force Impulse Imaging (ARFI) for the
      Determination of Liver Stiffness Using Transient Elastography as a Reference in
      Children.
AB  - PURPOSE: Transient elastography (Fibroscan((c)); (FS)) and acoustic radiation
      force impulse imaging (ARFI) represent noninvasive, user-friendly and quick
      methods providing an objective and reproducible measure of liver stiffness. The
      aim of the study was to evaluate cut-off values and performance of ARFI
      measurements in children using transient elastography as a reference.
      METHODS/PATIENTS: A total of 198 children were enrolled in this study. All
      patients underwent liver stiffness measurements with FS (FS-LS) as well as ARFI
      (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI
      in comparison to FS was studied. RESULTS: Significantly higher rates of
      successful measurements were found for ARFI compared to FS (198/198 (100%) vs.
      160/198 (80.8%); p<0.001). ARFI-SWV correlated significantly with FS-LS (r=0.751,
      p=0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.19+0.15
      m/s for patients with FS-LS<7.6 kPa); 1.34+0.22 m/s for patients with 7.6<FS
      LS<13.0 kPa); and 1.83+0.58 m/s for patients with FS-LS>13.0 kPa). ARFI-SWV cut
      off values were identified for no significant fibrosis (1.31 m/s; sensitivity
      61.8% and specificity 79.5%) and for liver cirrhosis (1.63 m/s; sensitivity 70.0%
      and specificity 97.4%). The median values of liver stiffness measured by FS were
      age-dependent in 90 children without liver diseases with 4.8, 5.6, and 5.7 kPa in
      children 0-5, 6-11, and 12-18 years, respectively.

PMID- 27689148
TI  - Image Fusion and Electromagnetic Needle Tracking for the Biopsy of Pelvic Lesions
      - Report of 2 Cases.

PMID- 27689150
TI  - Editorial.

PMID- 27689151
TI  - Common and Uncommon Presentation of Fluid within the Scrotal Spaces.
AB  - Ultrasonography(US) of the scrotum has been demonstrated to be useful in the
      diagnosis of fluid in the scrotal sac. Grayscale US characterizes the lesions as
      testicular or extratesticular and, with color Doppler, power Doppler and pulse
      Doppler, any perfusion can also be assessed. Cystic or encapsulated fluid
      collections are relatively common benign lesions that usually present as palpable
      testicular lumps. Most cysts arise in the epidydimis, but all anatomical
      structures of the scrotum can be the site of their origin. US may suggest a
      specific diagnosis for a wide variety of intrascrotal cystic and fluid lesions
      and appropriately guide therapeutic options. The paper reviews the current
      knowledge of ultrasound in conditions with fluid in the testis and scrotum. The
      review presents the applications of ultrasonography in the diagnosis of
      hydrocele, testicular cysts, epididymal cysts, spermatoceles, tubular ectasia,
      hernia and hematoceles. The aim of this paper is to provide a pictorial review of
      the common and uncommon presentation of fluid within the scrotal spaces. 

PMID- 27689149
TI  - Single Nucleotide Polymorphism-Based Analysis of Cell-Free Fetal DNA in 3000
      Cases from Germany and Austria.
AB  - BACKGROUND & PATIENT: Data from 3 008 patients, who underwent single-nucleotide
      polymorphism (SNP)-based noninvasive prenatal testing (NIPT) are presented.
      METHOD: The PanoramaTM test (Natera, San Carlos, CA) was used to analyze cell
      free fetal DNA from maternal blood for trisomies 21, 18, and 13, triploidy and
      sex-chromosome aneuploidies. RESULT: In 2 942 (97.8%) cases, a result was
      obtained. The average fetal fraction was 10.2%. A high-risk result for fetal
      aneuploidy was made for 65 (2.2%) cases. In 59 (90.8%) of these cases, invasive
      testing confirmed the aneuploidy. There were 6 false-positive cases. In the false
      positive group, the fetal fraction was significantly lower. The overall positive
      predictive value was 90.8%. No false-negative cases were reported but many
      patients in this study have not delivered yet. Therefore, exact data cannot be
      given for potential false-negative cases. CONCLUSION: SNP-based NIPT is a
      reliable screening method for evaluating the risk of aneuploidies of chromosomes
      21, 18 and 13. By using NIPT, the number of invasive procedures may be reduced
      significantly compared to maternal age and first-trimester screening.

PMID- 27689152
TI  - Positive Predictive Value of Abdominal Sonography in the Diagnosis of Ischemic
      Colitis.
AB  - AIM: The aim was to prospectively evaluate the positive predictive value of
      ultrasound in the diagnosis of ischemic colitis, with colonoscopy as the
      reference standard. METHODS: During a 2-year period we included consecutive
      patients over 50 years of age with sudden abdominal pain and/or rectal bleeding
      who underwent abdominal sonography in an emergency setting with a thickened
      segment of colon with a length of more than 10 cm. This clinical-sonographic
      triad was considered diagnostic for ischemic colitis. A thickened bowel location
      or color Doppler flow findings on ultrasound examination were evaluated but were
      not considered to make the diagnosis of ischemic colitis. Basic descriptive
      statistics were used to characterize the study patients. The positive predictive
      value was calculated as: number of patients with the definitive diagnosis of
      ischemic colitis (colonoscopic or follow-up)/number of patients with a
      sonographic diagnosis of ischemic colitis. RESULTS: A total of 48 patients had
      the clinical-sonographic triad; mean age: 74.3 years (range 54-90 years). The
      most frequent clinical manifestation was rectal bleeding (83% of the cases)
      followed by abdominal pain (81%) and diarrhea (45%). A total of 42 cases of
      ischemic colitis were confirmed by endoscopy (n=35) and biopsy (n=34) or clinical
      evaluation (n=7). The positive predictive value of the clinical-sonographic
      diagnosis of ischemic colitis was 87.5%. Thickening of the colon wall was
      detected on the left side in 35 patients with ischemic colitis, on the right side
      in 3 and pancolitis was identified in 5 patients. CONCLUSION: In an appropriate
      clinical setting, ultrasound has a high positive predictive value for the
      diagnosis of ischemic colitis.

PMID- 27689153
TI  - A Protocol for Improved Measurement of Arterial Flow Rate in Preclinical
      Ultrasound.
AB  - PURPOSE: To describe a protocol for the measurement of blood flow rate in small
      animals and to compare flow rate measurements against measurements made using a
      transit time flowmeter. MATERIALS AND METHODS: Measurements were made in rat and
      mice using a Visualsonics Vevo 770 scanner. The flow rate in carotid and femoral
      arteries was calculated from the time-average maximum velocity and vessel
      diameter. A correction factor was applied to correct for the overestimation of
      velocity arising from geometric spectral broadening. Invasive flow rate
      measurements were made using a Transonics system. RESULTS: Measurements were
      achieved in rat carotid and femoral arteries and in mouse carotid arteries. Image
      quality in the mouse femoral artery was too poor to obtain diameter measurements.
      The applied correction factor in practice was 0.71-0.77. The diameter varied by 6
      18% during the cardiac cycle. There was no overall difference in the flow rate
      measured using ultrasound and using transit-time flowmeters. The flow rates were
      comparable with those previously reported in the literature. There was wide
      variation in flow rates in the same artery in individual animals. Transit-time
      measurements were associated with changes of a factor of 10 during the typical 40
      min measurement period, associated with probe movement, vessel spasm, vessel
      kinking and other effects. CONCLUSION: A protocol for the measurement of flow
      rate in arteries in small animals has been described and successfully used in rat
      carotid and femoral arteries and in mouse carotid arteries. The availability of a
      noninvasive procedure for flow rate measurement avoids the problems with changes
      in flow associated with an invasive procedure.

PMID- 27689154
TI  - The Posterior Cerebral Artery and its Main Cortical Branches Identified with
      Noninvasive Transcranial Color-Coded Duplex Sonography.
AB  - PURPOSE: To differentiate PCA segments and cortical branches by means of
      transcranial color-coded duplex sonography (TCCD) and to measure flow parameters
      at rest and during visual stimulation. MATERIALS AND METHODS: 60 healthy subjects
      with a good acoustic temporal bone window were examined. The main stem of the PCA
      (P1, P2 and P3) and 4 main cortical branches - the anterior temporal artery
      (ATA), the occipital temporal artery (OTA), the parietooccipital artery (POA) and
      the calcarine artery (CA) - were assessed using an axial transtemporal approach.
      Systolic and diastolic blood flow velocities (BFVs) were recorded at rest and
      during visual stimulation. RESULTS: Identification of the P1 segment of the PCA
      was successful in 97.5% (117/120) of cases. The P2 and P3 segments were
      visualized in all cases. The 4 main cortical branches could be identified to
      varying degrees: ATA in 88%, OTA in 96%, POA in 69% and CA in 62%. There was an
      evoked flow response in the P2 main stem and in all cortical branches. The most
      pronounced increase in diastolic/systolic BFV after visual stimulation test was
      seen in the CA (42%/35%), followed by P2 (30%/24%), the POA (27%/27%), the OTA
      (16%/13%) and the ATA (9%/8%). CONCLUSION: Insonation through the temporal bone
      window with TCCD confidently allows the assessment of the P1 to P3 segments of
      the PCA as well as the 2 proximal branches, the ATA and the OTA. An ultrasound
      based classification of PCA anatomy and its cortical branches may be used as a
      noninvasive method for the evaluation of posterior circulation pathology.

PMID- 27689155
TI  - Point-of-Care Clinical Ultrasound for Medical Students.
AB  - PURPOSE: Our institution has recently implemented a point-of-care (POC)
      ultrasound training program, consisting of an e-learning course and systematic
      practical hands-on training. The aim of this prospective study was to evaluate
      the learning outcome of this curriculum. MATERIALS AND METHODS: 16 medical
      students with no previous ultrasound experience comprised the study group. The
      program covered a combination of 4 well-described point-of-care (POC) ultrasound
      protocols (focus assessed transthoracic echocardiography, focused assessment with
      sonography in trauma, lung ultrasound, and dynamic needle tip positioning for
      ultrasound-guided vascular access) and it consisted of an e-learning course
      followed by 4 h of practical hands-on training. Practical skills and image
      quality were tested 3 times during the study: at baseline, after e-learning, and
      after hands-on training. RESULTS: Practical skills improved for all 4 protocols;
      after e-learning as well as after hands-on training. The number of students who
      were able to perform at least one interpretable image of the heart increased from
      7 at baseline to 12 after e-learning, p<0.01, and to all 16 students after hands
      on-training, p<0.01. The number of students able to cannulate an artificial
      vessel increased from 3 to 8 after e-learning and to 15 after hands-on training.
      CONCLUSION: Medical students with no previous ultrasound experience demonstrated
      a considerable improvement in practical skill after interactive e-learning and 4
      h of hands-on training.

PMID- 27689158
TI  - Aortico-Left Ventricular Tunnel: Report of Two Prenatal Cases and Review of the
      Literature.

PMID- 27689157
TI  - "The Effervescent Gallbladder": A Rare Ultrasonographic Finding that Reflects the
      Presence of Gas within the Gallbladder.
AB  - This article deals with the "effervescent gallbladder", a rare ultrasonographic
      finding indicative of the presence of gas within the gallbladder. 3 cases are
      described and illustrated with photographs. Possible causes are reviewed and
      discussed. 

PMID- 27689156
TI  - Live Observation of Atherosclerotic Plaque Disruption in Apolipoprotein E
      Deficient Mouse.
AB  - AIM: The actual occurrence of spontaneous plaque rupture in mice has been a
      matter of debate. We report on an in vivo observation of the actual event of
      possible plaque disruption in a living ApoE(-/-) mouse. METHODS AND RESULTS:
      During live contrast-enhanced ultrasonography of a 50-week-old ApoE(-/-) male
      mouse, symptoms suggesting plaque disruption in the brachiocephalic artery were
      observed. Histological analysis confirmed the presence of advanced
      atherosclerotic lesions with dissections and intraplaque hemorrhage in the
      affected brachiocephalic trunk, pointing towards plaque rupture as the cause of
      the observed event. However, we did not detect a luminal thrombus or cap rupture,
      which is a key criterion for plaque rupture in human atherosclerosis. CONCLUSION:
      This study reports the real-time occurrence of a possible plaque rupture in a
      living ApoE(-/-) mouse.

PMID- 27689159
TI  - Investigation of Penile Conditions by Ultrasound and Contrast-Enhanced Ultrasound
      - Presentation of Three Clinical Cases.

PMID- 27689160
TI  - Editorial.

PMID- 27689161
TI  - Is Sonographic Assessment of Intratendinous Blood Flow in Achilles Tendinopathy
      Patients Reliable?: Consistency of Doppler Ultrasound Modes and Intra- and Inter
      observer Reliability.
AB  - PURPOSE: The purpose of this study was to investigate the consistency between
      different Doppler ultrasound (DU) modes as well as the intra- and inter-observer
      reliability of investigators with different experience level in assessing
      intratendinous blood flow (IBF) in Achilles tendinopathy patients. MATERIAL AND
      METHODS: 18 participants (36 Achilles tendons, AT) with Achilles tendinopathy (24
      AT) were examined with power Doppler ultrasound (PDU), colour Doppler ultrasound
      (CDU) and "Advanced Dynamic Flow" (ADF) (Toshiba Xario SSA-660 A; 14MHz
      transducer) by 2 investigators (experienced, EI; inexperienced, II) in a test
      retest design (M1/M2). A modified Ohberg score was used to quantify IBF. Data was
      analysed descriptively (absolute and relative). Consistency of the 3 modes was
      presented by Kendall's Coefficient of Concordance (Kendall's W). Intra- and inter
      observer reliability were calculated by use of Kendall's tau b correlation
      coefficient. RESULTS: IBF was detected in 79-92% of symptomatic AT and in 33-50%
      of contralateral asymptomatic AT. Comparing the 3 modes, Kendall's W ranged from
      0.97-0.98. Analysis of intra-observer reliability resulted in Kendall's tau 0.90
      0.92 for EI and 0.84-0.87 for II. Inter-observer reliability resulted in
      Kendall's tau 0.64-0.69 in M1 and 0.68-0.70 in M2. CONCLUSION: The very good
      consistency between PDU, CDU and ADF indicates a comparable applicability for
      assessing IBF in ATs. Intra-observer reliability was high for both investigators,
      independent of experience. The moderate inter-observer reliability reflects the
      challenge in sonographic detection of intratendinous blood flow (IBF) amount.

PMID- 27689162
TI  - Prenatal Risk Calculation (PRC) 3.0: An Extended DoE-Based First-Trimester
      Screening Algorithm Allowing For Early Blood Sampling.
AB  - AIM: Both previous versions of the German PRC algorithm developed by our group
      for routine first-trimester screening relied on the assumption that maternal
      blood sampling and fetal ultrasonography are performed at the same visit of a
      pregnant women. In this paper we present an extension of our method allowing also
      for constellations where this synchronization is abandoned through preponing
      blood sampling to dates before 11 weeks of gestation. METHODS: In contrast to the
      directly measured concentrations of the serum parameters PAPP-A and free beta
      hCG, the logarithmically transformed values could be shown to admit the
      construction of reference bands covering the whole range from 16 to 84 mm CRL
      [corresponding to 63 to 98 days of gestation]. Prior to determining reference
      limits from which the DoEs for each individual patient had to be calculated, the
      log concentrations of all PAPP-A and free beta-hCG values were transformed once
      more using the calibration approach established in 1 for the elimination of the
      influence of maternal weight. RESULTS: Although that part of the database which
      was available for estimating the reference bands for blood sampling times prior
      to 11 weeks of gestation was comparatively sparse (898 out of 186 215 pregnancies
      with euploid outcome), the key statistical characteristics of the extended risk
      calculation procedure turned out to be very satisfactory. Using the same cutoff
      value of 1:150 for the posterior risks of trisomy 21 and 13/18, the overall FPR
      (false positive rate) for diagnosing a T21 was found to be 3.42%. The
      corresponding DTR (detection rate) was obtained to be 86.8% and thus exceeded the
      DTR attained by PRC 2.0 for trisomy 21. For trisomies 13 and 18, the proportions
      of patients with calculated posterior risks exceeding the cutoff value of 1:150
      were obtained to be 1.60% (=FPR) and 86.4% (=DTR). CONCLUSION: Transforming the
      measured concentrations of PAPP-A and free beta-hCG to the logarithmic scale
      allows one to extend the DoE-based algorithm developed by the FMF Germany for
      diagnosing trisomies 21 and 13/18 in such a way that it can be applied to
      constellations where blood sampling is done before 11 weeks of gestation.

PMID- 27689163
TI  - EFSUMB Statement on Medical Student Education in Ultrasound [long version].
AB  - The European Federation of Societies for Ultrasound in Medicine and Biology
      (EFSUMB) recommends that ultrasound should be used systematically as an easy
      accessible and instructive educational tool in the curriculum of modern medical
      schools. Medical students should acquire theoretical knowledge of the modality
      and hands-on training should be implemented and adhere to evidence-based
      principles. In this paper we report EFSUMB policy statements on medical student
      education in ultrasound that in a short version is already published in
      Ultraschall in der Medizin 1. 

PMID- 27689164
TI  - Ultrasound Diagnosis of Hepatic Steatosis as a Surrogate for Atherosclerosis.

PMID- 27689165
TI  - Transcranial Color-coded Sonography to assess Collateral Posterior Pathways in a
      case of spontaneous Bilateral Carotid Arteries Dissection in the Absence of
      Ischaemic Event.

PMID- 27689166
TI  - Fibrous Pseudotumor of the Tunica Vaginalis of the Scrotum: Is there a Typical
      Ultrasound Pattern?

PMID- 27689167
TI  - Determining Tarsus Curvature in Relation To Direction of Gaze Using Non-contact
      Ultrasound Video Assistance.
AB  - PURPOSE: Plastic surgery on the eyelids for the purpose of aesthetic or
      functional correction requires precise knowledge of lid anatomy. Changes in the
      tarsal curvature of the upper eyelid relative to line of vision are important,
      particularly when a surgical correction of paralytic lagophthalmos is undertaken.
      We used a computer-based image-processing algorithm to establish a relationship
      between changes in the curvature of the tarsus relative to the line of vision.
      MATERIAL AND METHODS: A dynamic, ultrasound examination of the upper eyelids of
      100 participants (100 eyes) was performed transpalpebrally using a 7.5 MHz
      scanner with the patient looking straight ahead, away from and towards the
      midline of the body. A computer-aided examination of the upper eyelid tarsus was
      then performed, followed by the calculation of the radius of curvature of the
      tarsus relative to the line of vision in each position. RESULTS: Using regression
      of a Taylor polynomial, the shape of the tarsus was mapped by a quadratic
      function, and the change in tarsal curvature relative to line of sight could be
      demonstrated. CONCLUSION: With objective evidence of change in the tarsal
      curvature relative to the line of sight, this may influence the treatment of
      pathological changes in the upper eyelid.

PMID- 27689168
TI  - Editorial.

PMID- 27689170
TI  - Can New Ultrasound Signs Help in Identifying Follicular Variant of Papillary
      Carcinoma of Thyroid? - A Pilot Study.
AB  - AIM: To describe two new ultrasound signs for thyroid nodules - "nodule in
      nodule" and "hypoechoic internal septae" and assess their usefulness in
      differentiating follicular variant of papillary thyroid carcinoma (FVPTC) from
      benign thyroid nodules (BTN). METHODOLOGY: Ultrasound findings of 210 patients
      with histopathologically proven FVPTC (68 nodules, M:F=13:47 with mean age of
      39.5+/-11.9 years) and BTN (165 nodules, (M:F=41:109 with mean age of 44+/-11.3
      years) were retrospectively reviewed from PACS by a single radiologist blinded to
      the final diagnosis. Logistic regression analysis was performed to identify the
      best predictors of FVPTC and their diagnostic performance was assessed. RESULTS:
      The "nodule in nodule" sign was seen in 80.9% of FVPTC and only 12.1% of BTN. The
      "hypoechoic internal septae" sign was seen in 44.1% of FVPTC and 17% of BTN.
      Younger patients, heterogeneous echotexture, nodule in nodule sign, thick
      incomplete non-uniform halo and presence of significant nodes were the best
      predictors of FVPTC (p<0.05). The sensitivity, specificity, positive predictive
      value, negative predictive value, accuracy and relative risk for FVPTC given as
      odds ratio (95% CI) for heterogeneous echotexture and nodule in nodule sign which
      were the best 2 predictors of FVPTC were 91.2%, 81.8%, 67.3%, 95.7%, 84.5%, 46.5
      (18.5-117.4) and 80.9%, 87.7%, 74.3%, 91.2%, 86.2%, 32.5 (15.04-70.2),
      respectively. There was improvement in the specificity (91.5%) and accuracy
      (86.6%) when a combined criterion of heterogeneous echotexture and nodule in
      nodule sign was applied to predict FVPTC. CONCLUSION: The "nodule in nodule" sign
      is common in FVPTC and when combined with heterogeneous echotexture can
      differentiate FVPTC and BTN with high specificity.

PMID- 27689171
TI  - Very Early In-Utero Diagnosis of Walker-Warburg Phenotype: The Cutting Edge of
      Technology.
AB  - BACKGROUND: Walker-Warburg phenotype is a severe and lethal autosomal recessive
      disorder, belonging to a group of congenital malformations defined as abnormal
      pial basement membrane formation. So far, prenatal diagnosis was considered
      possible only during late pregnancy. METHODS: First trimester assessment of a
      pregnancy suspected to be affected by Walker-Warburg phenotype, using a high
      resolution transvaginal ultrasound probe (6-12 MHz), T2 MR imaging (1.5T),
      molecular genetics and histopathology. RESULTS: Very early diagnosis of the
      Walker-Warburg phenotype at 11 weeks of gestation proved possible by depicting
      the classic signs of this entity, confirmed by molecular genetics, post-abortion
      MR imaging and histopathology. CONCLUSION: Advancements in ultrasound equipment
      and technology, molecular genetics and histopathology have made very early
      detection of this syndrome possible, thus shedding new light on the natural
      history of this malformation.

PMID- 27689169
TI  - Ultrasonographic Differentiation of Lateral Elbow Pain.
AB  - Lateral elbow pain is often attributed to degenerative or posttraumatic
      impairment of the common extensor tendon. Ultrasonography assesses the soft
      tissue structures of the lateral elbow, allowing the differentiation between
      various underlying processes, including angiofibroblastic degeneration, hyaline
      degeneration, and inflammation, and exclusion of other possible causes of pain
      such as posterior interosseous and lateral antebrachial nerve compression.
      Furthermore, the real-time imaging nature of ultrasonography enables the
      detection of impingement of the lateral synovial fold, degenerative changes in
      the elbow recess, and elbow posterolateral instability during dynamic maneuvers.
      Ultrasonography is widely accessible and well tolerated by patients, making it a
      perfect method for establishing an initial diagnosis and monitoring the healing
      process. This review describes the possible causes of lateral elbow pain and
      their ultrasonographic differentiation. 

PMID- 27689174
TI  - Hepatic Epiteloid Hemangioendothelioma, a Diagnosis to keep in mind when finding
      Incidentalomas.

PMID- 27689175
TI  - Percutaneous or Open Surgical Biopsy in a Case of Symptomatic Neoplastic Brachial
      Plexus Infiltration?

PMID- 27689172
TI  - Assessment of Midfacial Hypoplasia in Down Syndrome Fetuses - Validity of a Two
      Line Approach and Introduction of a Novel Angle (Maxilla-Mandible-Nasion Angle).
AB  - PURPOSE: To scrutinize the validity of a novel angle (maxilla-mandible-nasion
      angle, MMN) as objective proof of midfacial hypoplasia in trisomy 21 fetuses.
      MATERIALS AND METHODS: Volume data sets of 2(nd) trimester fetuses were reviewed
      in this retrospective study. After achievement of the correct midsagittal
      position, the fetal profile line (FP line) and the mandibulo-maxillary line (MML)
      were applied and the resulting angle was calculated. Additionally, the prefrontal
      space ratio (PFSR) was assessed. Both measurements were obtained from 401 euploid
      fetuses and 42 fetuses with trisomy 21. Values for MMN and PFSR<5(th) percentile
      were considered abnormal. RESULTS: The study included 443 fetuses with a mean
      gestational age of 21.3 weeks (range: 14.0-26.3). The MMN angle sufficiently
      identified hypoplasia of the midface in trisomy 21 fetuses (mean: 14.6 degrees ;
      range: 10.1 degrees - 22.0 degrees ) compared to controls (mean: 20.5 degrees ;
      range: 17.3 degrees -23.7 degrees ; p<0.0001). Concomitantly, the PFSR of Down
      syndrome fetuses was significantly lower (mean: 0.53; range: 0.21-1.22) than in
      euploid individuals (1.38; range: 0.54-2.23; p<0.0001). CONCLUSION: Calculation
      of the novel MMN angle in 2(nd) trimester fetuses reliably allows rapid
      assessment of craniofacial anatomy in order to rule out the midfacial hypoplasia
      frequently found in trisomy 21.

PMID- 27689173
TI  - Objective Assessment of Cervical Stiffness after Administration of Misoprostol
      for Intrauterine Contraceptive Insertion.
AB  - PURPOSE: The goal of this study was to objectively quantify cervical stiffness in
      misoprostol users prior to IUC insertion and at follow-up consultation to
      evaluate the feasibility of assessing cervical stiffness and to study the
      influence of misoprostol on cervical softening. MATERIALS AND METHODS: This was a
      cross-sectional study that evaluated 40 women who wished to use the LNG IUS.
      These women were evaluated immediately before LNG IUS insertion and 6 weeks later
      at follow-up consultation. Participants received 200 MUg of misoprostol combined
      with 75 mg of diclofenac in a single tablet orally (Arthrotec forte 75/200((r)),
      Pfizer, USA) 6-12 h prior to insertion in "off label" use. On both occasions,
      cervical stiffness was determined using a novel medical device based on the
      aspiration technique. The Wilcoxon rank-sum and the Wilcoxon signed-rank test
      were applied to compare cervical stiffness assessments at insertion of the IUD
      and at follow-up. RESULTS: For the first time, cervical stiffness was
      quantitatively assessed in misoprostol users prior to IUD insertion, proving that
      the aspiration technique enables detection of pharmacologically induced cervical
      changes, and also that misoprostol has a detectable softening effect on cervical
      tissue. CONCLUSION: The clinical value of the detected cervical softening after
      misoprostol administration remains unclear. Aspiration measurements could be
      helpful in searching for the ideal candidate, the appropriate route, dosage and
      interval of misoprostol intake prior to IUC insertion.

PMID- 27689176
TI  - More to be Learned about Cotyledonoid Dissecting Leiomyoma.

PMID- 27689179
TI  - Editorial.

PMID- 27689177
TI  - 71-Year-Old Patient with Chronic Lymphocytic Leukemia (CLL) and Hypoechoic
      Nodular Spleen and Liver Lesions with Fatal Outcome: Presentation of Mucormycosis
      in B-Mode Imaging and Contrast-Enhanced Ultrasound (CEUS).

PMID- 27689178
TI  - Unilateral Stimulation of the Right Ovary in a 10-Year-Old Girl with Perforated
      Appendicitis.

PMID- 27689180
TI  - Cervical Sonoelastography and Cervical Length Measurement but not Cervicovaginal
      Interleukin-6 Are Predictors for Preterm Birth.

PMID- 27689182
TI  - Accuracy of Point-of-Care B-Line Lung Ultrasound in Comparison to NT-ProBNP for
      Screening Acute Heart Failure.
AB  - AIM: The objective of this pilot study was to determine the accuracy of point-of
      care B-line lung ultrasound in comparison to NT Pro-BNP for screening acute heart
      failure. MATERIALS AND METHODS: An 8-zone lung ultrasound was performed by
      experienced sonographers in patients presenting with acute dyspnea in the ED. AHF
      was determined as the final diagnosis by 2 independent reviewers. RESULTS:
      Contrary to prior studies, B-line ultrasound in our study was highly specific,
      but moderately sensitive for identifying patients with AHF. There was a strong
      association between elevated NT-proBNP levels and an increased number of B-lines.
      CONCLUSION: In conclusion, point-of-care lung ultrasound is a helpful tool for
      ruling in or ruling out important differential diagnoses in ED patients with
      acute dyspnea.

PMID- 27689181
TI  - Clinical Data as an Adjunct to Ultrasound Reduces the False-Negative Malignancy
      Rate in BI-RADS 3 Breast Lesions.
AB  - PURPOSE: Ultrasound (US) is a well-established diagnostic procedure for breast
      examination. We investigated the malignancy rate in solid breast lesions
      according to their BI-RADS classification with a particular focus on false
      negative BI-RADS 3 lesions. We examined whether patient history and clinical
      findings could provide additional information that would help determine further
      diagnostic steps in breast lesions. MATERIALS AND METHODS: We conducted a
      retrospective study by exploring US BI-RADS in 1469 breast lesions of 1201
      patients who underwent minimally invasive breast biopsy (MIBB) from January 2002
      to December 2011. RESULTS: The overall sensitivity and specificity of BI-RADS
      classification was 97.4% and 66.4%, respectively, with a positive (PPV) and
      negative predictive value (NPV) of 65% and 98%, respectively. In 506 BI-RADS 3
      lesions, histology revealed 15 malignancies (2.4% malignancy rate), which
      corresponds to a false-negative rate (FNR) of 2.6%. Clinical evaluation and
      patient requests critically influenced the further diagnostic procedure, thereby
      prevailing over the recommendation given by the BI-RADS 3 classification.
      CONCLUSION: Clinical criteria including age, family and personal history,
      clinical examination, mammography and patient choice ensure adequate diagnostic
      procedures such as short-term follow-up or MIBB in patients with lesions
      classified as US-BI-RADS 3.

PMID- 27689184
TI  - Dynamic Change of Focal Fatty Sparing in Non-Alcoholic Fatty Liver Disease after
      Treatment with Sitagliptin.

PMID- 27689183
TI  - Easy Pulsatile Phantom for Teaching and Validation of Flow Measurements in
      Ultrasound.
AB  - PURPOSE: To build a simple model to teach and validate non-pulsatile and
      pulsatile flow quantification in ultrasound. MATERIALS AND METHODS: The setting
      consists of the following connected components: (1) medical syringe pump
      producing an adjustable constant flow (ml/min), (2) modulator modifying constant
      flow to a reproducible pulsatile flow, (3) water tank containing a diagonal
      running silicone tube (0.5 mm inner diameter), and (4) a fixated ultrasound probe
      (L9 Linear Array 9 MHz, GE Logiq E9) measuring the flow inside the tube.
      Commercially available microbubbles suspended with physiological saline solution
      were used for ultrasonic visibility. Spectral Doppler of different flow profiles
      is performed. RESULTS: The syringe pump produces an adjustable, constant flow and
      serves as the reference standard. The filling volume of the tube system is 1.2
      ml. Microbubbles are very well detected by ultrasound and can be used as an easy
      and clean blood mimicking substance. The modulator generates different
      physiological and pathological flow profiles. Velocities are similar to those
      found within human blood vessels. Thus, it is possible to train and validate flow
      measurements in ultrasound. CONCLUSION: The model produces non-pulsatile and
      various pulsatile flow profiles and allows validation of flow measurements. The
      compact size permits easy and economic setup for flow measurements in research,
      skills lab and continuing education.

PMID- 27689185
TI  - Computed Tomographic Colonography Findings in Ileocecal Tuberculosis.

PMID- 27689186
TI  - Pancreatic Cystic Lesion with Baffling Fluid Levels of CEA and Amylase.

PMID- 27689187
TI  - A Rare Complication of Liver Hydatid Cyst Surgery: Budd-Chiari Syndrome.

PMID- 27689188
TI  - Cystic Pancreatic Lesion Discovered in the Setting of Abdominal Trauma: a
      Diagnostic Challenge.

PMID- 27689189
TI  - Toll-like Receptor 2 Signalling and the Lysosomal Machinery in Barrett's
      Esophagus.
AB  - BACKGROUND AND AIMS: Inflammation plays an important role in the development of
      esophageal adenocarcinoma and its metaplastic precursor lesion, Barrett's
      esophagus. Toll-like receptor (TLR) 2 signalling and lysosomal function have been
      linked to inflammation-associated carcinogenesis. We examined the expression of
      TLR2 in the esophagus and the effect of long-term TLR2 activation on
      morphological changes and expression of factors involved in lysosomal function in
      a Barrett's esophagus epithelium cell line. METHODS: TLR2 expression in normal
      squamous esophagus, reflux esophagitis, Barrett's esophagus and esophageal
      adenocarcinoma biopsies was assessed with Q-RT-PCR, in situ hybridization and
      immunohistochemistry. Barrett's esophagus epithelium cells (BAR-T) were incubated
      with acid and bile salts in the presence or absence of the TLR2 agonist Pam3CSK4
      for a period up to 4 weeks. Morphological changes were assessed with electron
      microscopy, while Q-RT-PCR was used to determine the expression of lysosomal
      enzymes (Cathepsin B and C) and factors involved in endocytosis (LAMP-1 and M6PR)
      and autophagy (LC3 and Rab7). RESULTS: TLR2 was expressed in normal squamous
      esophagus, reflux esophagitis, Barrett's esophagus but was most prominent in
      esophageal adenocarcinoma. Long-term TLR2 activation in acid and bile salts
      exposed BAR-T cells resulted in more and larger lysosomes, more mitochondria and
      increased expression of LAMP-1, M6PR, Cathepsin B and C when compared to BAR-T
      cells incubated with acid and bile salts but no TLR2 agonist. Factors associated
      with autophagy (LC3 and Rab7) expression remained largely unchanged. CONCLUSION:
      Activation of TLR2 in acid and bile salts exposed Barrett epithelium cells
      resulted in an increased number of mitochondria and lysosomes and increased
      expression of lysosomal enzymes and factors involved in endocytosis.

PMID- 27689191
TI  - The Efficacy of Virtual Chromoendoscopy in the Diagnosis of Portal Hypertensive
      Gastropathy.
AB  - BACKGROUND: Diagnosis of portal hypertensive gastropathy (PHG) is based on
      endoscopic criteria. I-scan technology, a new technique of virtual
      chromoendoscopy, increases the diagnostic accuracy for lesions in the
      gastrointestinal tract. AIM: To establish the role of i-scan endoscopy in the
      diagnosis of PHG. METHOD: In this prospective study, endoscopic examination was
      conducted first by using white light and after that i-scan 1 and i-scan 2
      technology in a group of 50 consecutive cirrhotic patients. The endoscopic
      diagnostic criteria for PHG followed the Baveno criteria. The interobserver
      agreement between white light endoscopy and i-scan endoscopy was determined using
      Cohen's kappa statistics. RESULTS: Forty-five of the 50 patients met the
      diagnostic criteria for PHG when examined by i-scan endoscopy and 39 patients
      were diagnosed with PHG by white light endoscopy. The strength of agreement
      between the two methods for the diagnosis of PHG was moderate (k=0.565; 95%CI
      0.271-0.859; p<0.001). I-scan 1 classified the mosaic pattern better than classic
      endoscopy; i-scan 2 described better the red spots. CONCLUSION: I-scan
      examination increased the diagnostic sensitivity of PHG. The diagnostic criteria
      (mosaic pattern and red spots) were easier to observe endoscopically using i-scan
      than in white light.

PMID- 27689190
TI  - A Novel Potassium-Competitive Acid Blocker Improves the Efficacy of
      Clarithromycin-containing 7-day Triple Therapy against Helicobacter pylori.
AB  - BACKGROUND AND AIMS: In Japan, 7-day triple therapy for Helicobacter pylori
      including clarithromycin (CAM) was approved in 2000. However, antibiotic
      resistance subsequently reduced this rate to an unacceptable level (70%).
      Vonoprazan, an orally bioavailable potassium-competitive acid blocker (P-CAB),
      was approved in Japan in 2014. This could improve eradication rates by increasing
      the intragastric pH, thus increasing bacterial antibiotic susceptibility. This
      study compared the efficacy of 7-day triple therapies that included CAM and
      vonoprazan or proton pump inhibitor (PPI). METHODS: We prospectively analyzed H.
      pylori eradication rates in 146 patients receiving 7-day triple therapy
      containing P-CAB (April 2015 to September 2015), and in a retrospective cohort of
      1,305 patients who received 7-day triple therapy containing a PPI (April 2011 to
      September 2015). RESULTS: H. pylori was eradicated in a significantly higher
      number of P-CAB-treated patients (89.7% [131/146]) than PPI-treated patients
      (73.9% [965/1305]; p < 0.05). The eradication rates in P-CAB-treated CAM
      sensitive and CAM-resistant bacteria were 100% (44/44) and 87.5% (28/32),
      respectively, which were significantly higher than the corresponding rates in PPI
      treated patients (88.0% [22/25] and 53.8% [7/13], p < 0.05). CONCLUSION: P-CAB
      improved the efficacy of CAM-containing 7-day triple therapy and would be a
      valuable first-line treatment for H. pylori infection.

PMID- 27689192
TI  - Superiority of a Split-dose Regimen of Sodium Picosulfate/Magnesium Citrate
      (SPMC) in Comparison to a Prior-day Schedule (AM/PM) for Colonoscopy Preparation.
      A Randomized Single-blinded Study.
AB  - BACKGROUND AND AIMS: Split-dose regimens are generally recommended for bowel
      cleansers. However, other regimens still remain in the summary of product
      characteristics of some bowel cleansers in Europe. The aim of this study is to
      compare the efficacy and safety of a split-dose regimen of sodium
      picosulfate/magnesium citrate (SPMC) with a prior-day schedule (AM/PM). METHODS:
      Multicenter, randomized (EudraCT no. 2013-001620-20), endoscopist-blinded,
      parallel study, carried out in subjects 18 years or older undergoing elective
      colonoscopy. The primary endpoint was the bowel cleansing assessment using a
      binary transformation (adequate/inadequate) of the Global Preparation Assessment
      (GPA) scale. Additional parameters analyzed were the segmental assessment of
      bowel cleansing (RSS), the adenoma detection rate and safety evaluations.
      RESULTS: 315 subjects comprised the ITT set. A significantly higher proportion of
      patients in the split-dose regimen had an adequate bowel preparation (AM/PM:
      30.8% vs split-dose: 79.9%; p<0.0001). The mean global RSS was significantly
      lower in the split-dose group (AM/PM: 5.0 [SD: 2.91] vs split-dose: 2.6 [SD:
      2.14]; p<0.0001). Flat polyps were detected in a higher proportion of subjects in
      the split-dose group compared with the AM/PM group (AM/PM: 16.0% vs split-dose:
      22.0%). Both regimens were equally safe and well tolerated, with no serious
      treatment-emergent adverse events or discontinuations due to adverse events.
      CONCLUSION: A split-dose regimen of SPMC is superior to the AM/PM regimen
      administered the day before colonoscopy. Split regimen of SPMC should be
      considered the standard of use.

PMID- 27689193
TI  - Should we Investigate Gastroenterology Patients for Pancreatic Exocrine
      Insufficiency? A Dual Centre UK Study.
AB  - BACKGROUND AND AIMS: Pancreatic exocrine insufficiency may be under recognised in
      gastroenterological practice. We aimed to identify the prevalence of pancreatic
      insufficiency in secondary care gastroenterology clinics and determine if co
      morbidity or presenting symptoms could predict diagnosis. A secondary aim was to
      assess response to treatment. METHODS: A dual centre retrospective analysis was
      conducted in secondary care gastroenterology clinics. Patients tested for
      pancreatic exocrine insufficiency with faecal elastase-1 (FEL-1) between 2009 and
      2013 were identified in two centres. Demographics, indication and co-morbidities
      were recorded in addition to dose and response to pancreatic enzyme replacement
      therapy. Binary logistic regression was used to assess if symptoms or co
      morbidities could predict pancreatic insufficiency. RESULTS: 1821 patients were
      tested, 13.1% had low FEL-1 (<200ug/g). This prevalence was sub-analysed with
      5.4% having FEL-1 100-200ug/g (mild insufficiency) and 7.6% having faecal
      elastase readings <100ug/g. Low FEL-1 was most significantly associated with
      weight loss or steatorrhoea. Co-morbidity analysis showed that low levels were
      significantly associated with excess alcohol intake, diabetes mellitus or human
      immunodeficiency virus; 80.0% treated with enzyme supplements reported
      symptomatic benefit with no difference in response between high and low dose
      supplementation (p=0.761). CONCLUSION: Targeting the use of FEL-1 in individuals
      with specific symptoms and associated conditions can lead to improved recognition
      of pancreatic exocrine insufficiency in a significant proportion of secondary
      care patients. Intervening with lifestyle advice such as smoking cessation and
      minimising alcohol intake could improve outcomes. In addition, up to 80% of
      patients with low faecal elastase respond to supplementation.

PMID- 27689194
TI  - Single Nucleotide Polymorphisms within the 8Q24 Region are Not Associated with
      the Risk of Intraductal Papillary Mucinous Neoplasms of the Pancreas.
AB  - BACKGROUND AND AIMS: Intraductal papillary mucinous neoplasms (IPMNs) of the
      pancreas have been reported to be associated with an increased risk of developing
      extra-pancreatic malignancies. A common genetic background has been hypothesised
      to be responsible for such an association. Human chromosomal region 8q24 has been
      associated with many types of cancer. The majority of these associations lie at
      approximately 128 Mb on chromosome 8. We conducted a study in order to examine
      the association between IPMN and single nucleotide polymorphisms (SNPs) from the
      8q24 region, namely rs10505477, rs6983267, rs7014346, rs6993464, previously
      reported to influence general cancer susceptibility. METHODS: The study was
      performed on 117 IPMN cases and 231 controls. Cases were enrolled at the
      Digestive Endoscopy Unit, Policlinico Agostino Gemelli from January, 2010 to
      June, 2011, with either a prevalent or incident IPMN diagnosis. Status of SNPs
      was determined using a StepOne Real-time PCR system (Applied Biosystems) and
      TaqMan SNP Genotyping AssayTM 40X. Unconditional multiple logistic regression
      models were used to estimate odds ratios and 95% confidence intervals for the
      association of selected SNPs and IPMNs. RESULTS: Cases were more likely to report
      a 1st degree family history of cancer (p<0.001), as well as heavy smoking
      (p=0.001) and heavy drinking habits (p<0.001). No significant association was
      observed between IPMN and selected SNPs. The results were confirmed also when
      stratified according to any 1st-degree family history of cancer. CONCLUSION:
      Patients with IPMN do not have a higher prevalence of SNPs in the human
      chromosomal region 8q24 in respect to the control population.

PMID- 27689195
TI  - Pre-operative Diagnosis of Pancreatic Neuroendocrine Tumors with Endoscopic
      Ultrasonography and Computed Tomography in a Large Series.
AB  - BACKGROUND AND AIMS: Diagnosis of pancreatic neuroendocrine tumors (p-NETs) is
      frequently challenging. We describe a large series of patients with p-NETs in
      whom both pre-operative Computed Tomography (CT) and Endoscopic Ultrasonography
      (EUS) were performed. METHODS: This was a retrospective analysis of prospectively
      collected sporadic p-NET cases. All patients underwent both standard
      multidetector CT study and EUS with fine-needle aspiration (FNA). The final
      histological diagnosis was achieved on a post-surgical specimen. Chromogranin A
      (CgA) levels were measured. RESULTS: A total of 80 patients (mean age: 58 +/-
      14.2 years; males: 42) were enrolled. The diameter of functioning was
      significantly lower than that of non-functioning p-NETs (11.2 +/- 8.5 mm vs 19.8
      +/- 12.2 mm; P = 0.0004). The CgA levels were more frequently elevated in non
      functioning than functioning pNET patients (71.4% vs 46.9%; P = 0.049). Overall,
      the CT study detected the lesion in 51 (63.7%) cases, being negative in 26
      (68.4%) patients with a tumor </=10 mm, and in a further 3 (15%) cases with a
      tumor diameter </=20 mm. CT overlooked the pancreatic lesion more frequently in
      patients with functioning than non-functioning p-NETs (46.5% vs 24.3%; P =
      0.002). EUS allowed a more precise pre-operative tumor measurement, with an
      overall incorrect dimension in only 9 (11.2%) patients. Of note, the EUS-guided
      FNA suspected the neuroendocrine nature of tumor in all cases. CONCLUSIONS: Data
      of this large case series would suggest that the EUS should be included in the
      diagnostic work-up in all patients with a suspected p-NET, even when the CT study
      was negative for a primary lesion in the pancreas.

PMID- 27689196
TI  - Body Composition Changes in Patients with Chronic Hepatitis C.
AB  - AIMS: We aimed to quantify global and regional body composition changes in
      chronic hepatitis C (CHC) patients, compare them to healthy controls and identify
      possible association between body composition changes and CHC. To our knowledge,
      this study is the first one comparing CHC patients to controls with regard to
      soft tissue body composition changes. METHODS: We assessed 60 CHC patients and 60
      healthy controls by Dual Energy X-Ray Absorptiometry. Soft tissue and bone body
      composition parameters were compared between the groups (using the Mann-Whitney
      test). These parameters were correlated (using Spearman's rank correlation
      coefficient - rho) with independent variables (age, gender, body mass index -
      BMI, cigarette smoking, time since CHC diagnosis, viral load, fibrosis grade,
      type of treatment, time of treatment) for the entire CHC group and also for
      subgroups according to gender. RESULTS: Total fat mass, trunk fat mass and
      percent body fat were lower in CHC patients as compared to controls. Several risk
      factors were associated with the reduced fat mass: low BMI, cigarette smoking and
      peginterferon alpha 2a plus ribavirin treatment. Peginterferon alpha 2a and
      ribavirin treatment negatively correlated with lean body parameters, especially
      in CHC males group. Bone mineral density (BMD) was lower as compared to controls
      and was correlated with low BMI, cigarette smoking and peginterferon alpha 2a and
      ribavirin treatment. CONCLUSIONS: Patients with CHC have an acquired type of
      lipodystrophy (particularly in the trunk region), and also a reduced BMD as
      compared with controls. A low BMI, cigarette smoking and peginterferon alpha 2a
      and ribavirin therapy were associated with a low fat mass and low BMD.

PMID- 27689197
TI  - Accuracy of the ElastPQ Technique for the Assessment of Liver Fibrosis in
      Patients with Chronic Hepatitis C: a "Real Life" Single Center Study.
AB  - BACKGROUND AND AIMS: Noninvasive assessment of liver stiffness has been
      increasingly used to evaluate fibrosis instead of liver biopsy, especially in
      patients with chronic viral hepatitis. The aim of this study was to assess the
      performance in staging liver fibrosis of the updated ElastPQ(r) technique (EPIQ7
      ultrasound system, Philips Healthcare, Bothell, WA, USA) in the "real life"
      setting by using the FibroScan as the reference standard and to understand
      whether the use of the quality criteria improves the performance of the
      technique. METHODS: This was a cross-sectional study: 278 patients affected by
      chronic hepatitis C referred for liver stiffness measurement with the
      FibroScan(r) 502 Touch device (Echosens, Paris, France) underwent measurements
      also with the ElastPQ(r) technique. For the assessment of significant fibrosis
      (F>/=2), advanced fibrosis (F>/=3) and cirrhosis (F=4), respectively, we used the
      cutoffs of 7.0, 9.5 and 12.0 kPa. The diagnostic performance of ElastPQ(r) was
      assessed using the area under the ROC (AUROC) curve analysis and was evaluated
      overall and for cases with (a) 10 measurements and IQR/M</=30%, (b) 5
      measurements and IQR/M </=30%, (c) 10 measurements and IQR/M>30%, (d) 5
      measurements and IQR/M>30%. RESULTS: The optimal cutoffs of ElastPQ(r) for
      significant fibrosis, advanced fibrosis and cirrhosis were 6.43, 9.54 and 11.34
      kPa, respectively. For measurements with an IQR/M</=30%, there was no
      statistically significant decrease in sensitivity between 10 and 5 measurements
      (p=0.26, p=0.09, p=0.71, for F>/=2, F>/=3, and F=4, respectively). CONCLUSION:
      The ElastPQ(r) technique is reliable and accurate for staging liver fibrosis. The
      number of measurements does not affect the performance.

PMID- 27689199
TI  - Analysis of p53 Protein Expression in Hepatocellular Carcinoma.
AB  - BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) has a growing incidence and
      studies regarding the risk factors or pathogenesis for this type of carcinoma
      benefit special interest. This study evaluates the correlations between p53
      protein expression and clinical and laboratory factors in patients with HCC.
      METHODS: The study group included 76 patients diagnosed with HCC, either by
      biopsy or after surgical resection (with curative intent). Immunohistochemistry
      for p53 protein assessment was performed in all patients. Correlations between
      the protein 53 expression and age, tumour size, viral infection, liver cirrhosis
      were performed using the chi-square test (Pearson's chi-square) together with the
      contingency coefficient Kendall's coefficient in the tau-b form. RESULTS: In the
      study group, 51 patients were male (67%) and 25 female (33%). Cirrhosis due to
      hepatitis virus B or C infection (in a proportion of 63% of the study group) was
      not significantly associated with the presence of HCC. Altered expression of p53
      protein was observed in 69 patients (91%). The relationship between p53 protein
      expression and patient sex (p=0.067), age (p=0.531), tumour size (p=0.270),
      presence of hepatitis B and C viral infections (p=0.7), and of liver cirrhosis
      (p=0.511) was not statistically significant. CONCLUSION: The p53 protein
      expression was not significantly associated with the demographic characteristics
      of the patients, tumour size, presence of viral B and C infections or liver
      cirrhosis.

PMID- 27689200
TI  - Mucin Genes Expression in the Intestine of Crohn's Disease Patients: a Systematic
      Review and Meta-analysis.
AB  - BACKGROUND AND AIMS: The mucus layer of the intestinal tract is the main barrier
      between luminal microbes and the mucosa, and has an essential role in the body
      defense mechanisms. Previous research could not establish consistent results for
      mucin genes expression in Crohn's disease (CD) patients. In this meta-analysis we
      looked at the mucin expression in CD patients and compared it with healthy
      controls. METHOD: English medical literature searches were conducted for mucin
      expression in the mucosa of the ileum and colon of CD patients and compared it
      with normal mucosa. Case-control studies were included. Meta-analysis was
      performed by using Comprehensive meta-anaslysis software. Pooled odds ratios and
      95% confidence intervals were calculated. RESULTS: We found 160 eligible studies.
      Twenty studies were rejected because they have been performed in animals or did
      not have full text, and 134 studies were excluded because of language, being
      editorials, review articles, or because of duplications. We were left with 6 case
      control studies from 4 countries that fulfilled the inclusion criteria, published
      till 31.12.2015. No significant heterogeneity was demonstrated: Q = 149.256, df
      (Q) = 40.00, I2= 73.2% (less than 75%). We found a decrease of 34% in the total
      mucin expression in CD patients (Odds Ratio 0.660, 95% CI 0.486-0.897, P =
      0.008). We also found a significantly decreased expression in CD patients for
      MUC5AC, MUC5B and MUC7. CONCLUSION: We demonstrated a global decrease in mucin
      expression in CD patients when compared with healthy controls.

PMID- 27689198
TI  - Prognostic Value of Metabolic Liver Function Tests: a Study on 711 Cirrhotic
      Patients.
AB  - BACKGROUND AND AIMS: The prognosis of cirrhotic patients is usually assessed by
      Child-Pugh and MELD scores. Metabolic liver function tests such as aminopyrine
      breath test (ABT) and indocyanine green clearance (IGC) have been shown to reveal
      hepatocellular dysfunction. The aim of this retrospective study was to compare
      the prognostic value of the MELD score, Child-Pugh score, ABT and IGC in a large
      cohort of cirrhotic patients. METHODS: Between January 1996 and June 2008, 711
      cirrhotic patients were included and the primary endpoint was survival without
      LT. The ROC curves with c-statistics, correlation coefficient and survival were
      calculated. RESULTS: Metabolic function tests and scores were strongly
      correlated. At the time of evaluation, 111 patients had died and 520 had received
      a transplant. Prognostic ability (estimated by the AUROC curve) to predict
      survival without LT at 6 months was 0.662, 0.691, 0.738 and 0.715 for ABT, IGC,
      Child-Pugh score and MELD score, respectively. Similarly, at 1 year, AUROC was
      0.738 for Child-Pugh score, 0.716 for MELD score, 0.693 for IGC clearance and
      0.651 for ABT. CONCLUSIONS: Our results strongly confirm that IGC and ABT have a
      high prognostic value in cirrhotic patients, similar to Child-Pugh and MELD
      scores. They could be developed to routinely evaluate the prognosis of patients
      in addition to clinical and biochemical data.

PMID- 27689201
TI  - Psychological Interventions for Irritable Bowel Syndrome.
AB  - Irritable bowel syndrome (IBS) patients often present psychoform symptoms or
      psychiatric disorders. Among the psychological factors studied in IBS patients,
      two seem to influence mostly its severity: catastrophizing and somatization.
      Somatization is an independent risk factor for IBS. In addition, somatization
      more than the severity of IBS influences the way the patients perceive their
      illness, the outcome and the efficacy of treatment. Irritable bowel syndrome
      patients demonstrate greater catastrophizing scores than controls, and pain
      catastrophizing is a significant predictor of gastrointestinal symptoms related
      to pain. In this context we analysed the data regarding the efficacy of two
      psychological treatments in IBS: cognitive behavioral therapy and hypnosis.
      Cognitive behavioral therapy is focused on replacing maladaptive coping
      strategies with more positive cognitions and behaviors. Several studies showed
      that cognitive behavioral therapy is effective in reducing bowel symptoms in IBS,
      both post-treatment and short-term follow-up. Gut-directed hypnotherapy has
      beneficial short-term effects in improving gastrointestinal symptoms of patients
      with IBS, and the results are maintained after one year in half of the patients.
      Psychological treatments are a suitable option for selected IBS patients. 

PMID- 27689202
TI  - Gastrointestinal Side Effects of Post-Transplant Therapy.
AB  - Modern immunosuppressive therapy has produced a real revolution in renal and
      organ transplantation but it comes with the price of multiple side effects. There
      are many gastrointestinal (GI) complications that are the consequence of
      transplant immunosuppressant medication. In fact, for any immunosuppressant
      therapy, certain standardized precepts and attitudes that aim to reduce the
      incidence and the impact of the medication side effects must be applied. Many
      patients undergo renal transplantation and the physicians have to be aware of the
      advantages and the risks associated. This article reviews the main GI
      complications that may arise as a consequence of immunosuppressive therapy after
      solid organ transplantation, focusing on renal and renal/pancreas
      transplantation, as well as the ways in which the incidence of these
      complications can be reduced. Management of the post-transplant therapy is
      mandatory in order to increase not only the grafts' and the patients' survival,
      but also their quality of life by the occurrence of fewer complications. 

PMID- 27689203
TI  - Magnetic Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy.
AB  - Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver,
      ranking as the second most common cause of death from cancer worldwide. Magnetic
      nanoparticles (MNPs) have been used so far in tumor diagnosis and treatment,
      demonstrating great potential and promising results. In principle, three
      different approaches can be used in the treatment of tumors with
      superparamagnetic iron oxide nanoparticles: magnetically induced hyperthermia,
      drug targeting and selective suppression of tumor growth. This review focuses on
      the use of iron oxide nanoparticles for the diagnosis and treatment of liver
      cancer and offers a walkthrough from the MNPs imaging applicability to further
      therapeutic options, including their potential flaws. The MNP unique physical and
      biochemical properties will be mentioned in close relationship to their
      subsequent effects on the human body, and, also, their toxic potential will be
      noted. A presentation of what barriers the MNPs should overcome to be more
      successful will conclude this review. 

PMID- 27689204
TI  - Serendipity in Refractory Celiac Disease: Full Recovery of Duodenal Villi and
      Clinical Symptoms after Fecal Microbiota Transfer.
AB  - Treatment of refractory celiac disease type II (RCD II) and preventing the
      development of an enteropathy associated T-cell lymphoma in these patients is
      still difficult. In this case report, we describe a patient with RCD II who
      received fecal microbiota transfer as treatment for a recurrent Clostridium
      difficile infection, and remarkably showed a full recovery of duodenal villi and
      disappearance of celiac symptoms. This case suggests that altering the gut
      microbiota may hold promise in improving the clinical and histological
      consequences of celiac disease and/or RCD II. 

PMID- 27689205
TI  - Non-gastric Gastrointestinal Xanthomas: Case Series and Literature Review.
AB  - Gastrointestinal xanthomas are infrequent non-neoplastic lesions characterized by
      the accumulation of foam cells in the lamina propria. They are commonly seen in
      association with dyslipidemia, chemotherapy or radiotherapy, and infections in
      immunosuppressed patients. However, no clear connection to hyperlipidemia has
      been found. They occur more frequently in the stomach, and are very rare in the
      small bowel and esophagus. We identified all cases of non-gastric xanthoma or
      xanthomatosis reported in the English literature by searching the PubMed database
      and retrospectively reviewed the clinical, endoscopic, and histopathologic
      features of the 11 cases of non-gastric gastrointestinal xanthomas diagnosed in
      our hospital. Nine lesions were located in the large bowel, one in the duodenum
      and one in the esophagus. All xanthomas were small (<5 mm) sessile polyps except
      the esophageal xanthoma, which measured 13 mm. Two cases in the large bowel and
      the case in the small bowel were multiple. Most patients with large bowel
      xanthomas had hypercholesterolemia, unlike esophageal and small bowel cases. The
      esophageal lesion occurred in a patient with a history of partial fundoplication
      due to gastroesophageal reflux disease and the small bowel case was associated to
      chronic atrophic gastritis with intense activity. In our search of the English
      literature, we found 19 cases of xanthoma or xanthomatosis in the esophagus, 13
      cases in the small bowel and 61 cases in the large bowel. In conclusion,
      gastrointestinal xanthomas, other than the gastric ones, are rare, and are
      usually incidental findings. 

PMID- 27689206
TI  - Therapeutic Challenges for Symptomatic Portal Cavernoma Cholangiopathy.
AB  - Although transjugular intrahepatic portosystemic shunts are most frequently used
      for the management of portal hypertension, the surgical approach is preferred for
      symptomatic portal cavernoma cholangiopathy. We present the case of a 25-year old
      female patient with a portal cavernoma secondary to catheterization of the
      umbilical vein at birth. She had had two episodes of esophageal variceal
      bleeding, successfully treated by endoscopic banding. and an episode of acute
      cholangitis secondary to portal cavernoma cholangiopathy. Endoscopic
      sphincterotomy and biliary stenting were performed, and were followed by repeated
      episodes of biliary stent occlusion. The last biliary drainage procedure
      triggered a massive hemobilia. Since endoscopic therapy was ineffective, a
      surgical mesocaval shunt with graft interposition and splenectomy was performed
      with favorable outcome. In selected cases, the mesocaval shunting plays an
      essential role in the treatment of portal cavernoma cholangiopathy even in the
      era of interventional radiology. 

PMID- 27689207
TI  - Multimodal Therapy including Yttrium-90 Radioembolization as a Bridging Therapy
      to Liver Transplantation for a Huge and Locally Advanced Intrahepatic
      Cholangiocarcinoma.
AB  - Treatment of intrahepatic cholangiocarcinoma remains a major challenge. For an
      unresectable lesion without extrahepatic spread, liver transplantation could be a
      potential solution but it is still associated with poor oncologic results owing
      to the absence of effective neoadjuvant treatment. We report the case of a young
      man with locally advanced intrahepatic cholangiocarcinoma presenting with
      multiple intrahepatic metastases and vascular structure involvement. The lesion
      was significantly downstaged by a multimodal therapy including intra-arterial
      Yttrium-90 radioembolization, systemic chemotherapy and external radiotherapy,
      allowing liver transplantation. Three years after the procedure, oncologic
      outcome is excellent with no sign of recurrence. Multimodal therapy including
      Yttrium-90 radioembolization could be relevant as neoadjuvant treatment before
      liver transplantation for unresectable intrahepatic cholangiocarcinoma. 

PMID- 27689208
TI  - A potential impact of Helicobacter pylori infection on minimal hepatic
      encephalopathy pathobiology.

PMID- 27689209
TI  - Reply.

PMID- 27689210
TI  - Feasibility of volumetric laser endomicroscopy in Barrett's esophagus with
      dysplasia and in post-ablation surveillance.

PMID- 27689211
TI  - Occurrence of hepatocellular carcinoma 13 years after successful antiviral
      treatment for HCV infection.

PMID- 27689212
TI  - Mesalazine in preventing acute diverticulitis occurrence: a meta-analysis of
      randomized controlled trials.

PMID- 27689213
TI  - Henoch Schonlein purpura and Clostridium difficile infection: a hematologist's
      point of view.

PMID- 27689214
TI  - Reply.

PMID- 27689215
TI  - In Memoriam. Mihai Voiculescu (1945-2016).

PMID- 27689222
TI  - [Surgical treatment of lumbar disc herniation].
AB  - OBJECTIVE: Herniated disc tissue removal to decompress the spinal nerve/cauda
      equina. Minimization of iatrogenic trauma and associated injuries. INDICATIONS:
      Conservative treatment did not sufficiently improve clinical symptoms. This is
      true for progressive or persisting neurological deficits, as well as for
      persisting pain which alters the quality of the patient's life. Results of
      surgery are strongly dependent on the preoperative duration of symptoms.
      Paramount is the "timing" of surgery: poorer surgical results associated with
      increasing preoperative duration of symptoms. CONTRAINDICATIONS: Conservative
      treatment modalities have not been exhausted. SURGICAL TECHNIQUES: There are 2
      technologies (endoscopic/microsurgical) and 5 different approach strategies
      (endoscopic: interlaminar, transforaminal; microsurgical: interlaminar,
      translaminar, extraforaminal), whereby the choice is determined by morphology and
      location of the herniated disc. All techniques are minimally invasive and lead to
      comparable clinical results. POSTOPERATIVE MANAGEMENT: For all techniques,
      patients are mobilized early. Light sports activities allowed after 2 weeks and
      return to work after about 4 weeks. RESULTS: Good clinical outcomes in meta
      analyses/large case series are between 80-95 %.

PMID- 27689223
TI  - [Autonomy and welfare in intensive care medicine : Practical approach in
      difficult situations].
AB  - In intensive care units far-reaching decisions are often made at short notice
      that require the consent of the informed patient. If this is not possible due to
      the patient's condition, physicians and legal representatives must ascertain the
      previously expressed or presumed will of the patient and act accordingly. The
      legal principles are specified in the Patient Advance Directives Act and the
      Patient Rights Act. Any indications for medical treatment need a clearly defined
      aim of the therapy, which can be questioned during the progress of the disease.
      To avoid conflicts between patient autonomy and medical treatment, the aims of
      therapy must be regularly discussed with the patient, representatives or
      relatives and documented in a written form. Checklists can be useful for
      structured consultations, to promote transparency and to avoid misunderstandings.
      Ethics consultations can help to deescalate critical situations.

PMID- 27689224
TI  - [Surgical innovations require testing in controlled clinical studies].

PMID- 27689225
TI  - [Local health study : Outreach medical services for female sex workers in
      Bochum].
AB  - BACKGROUND: Inadequate access to prevention and medical treatment for female sex
      workers (SW) represents a challenge for the German health system. Accessibility
      and care for SW in Bochum (Germany) through a cooperation between the
      Interdisciplinary Immunology Outpatient Clinic, Center for Sexual Health and
      Medicine of St. Josef's Hospital, the Bochum health department and the Madonna
      e.V. was the focus of this work. PATIENTS AND METHODS: Medical outreach services
      were provided for the diagnosis of sexually transmitted infections (STI) in SW in
      brothels in Bochum between August 2013 and January 2014. After clarification and
      verbal consent from the SW, free HIV, syphilis, chlamydia, gonorrhea and
      trichomoniasis tests were offered and carried out using pseudonyms for the SW.
      RESULTS: A total of 112 SW were reached (up to 55.4 % within the framework of the
      STI Outreach Study). Of the SW, 94.6 % had an immigrant background. The majority
      (61.3 %) of SW were between 20 und 29 years old. Only 19.0 % of the collective
      had health insurance. The following STIs were diagnosed: 12.5 % chlamydia, 6.2 %
      syphilis, 3.6 % gonorrhea, 3.6 % trichomoniasis, and 0.9 % HIV. These results
      were compared with results from STI studies in SW in Germany. Treatment was
      performed in accordance with the standards of the German STI Society. CONCLUSION:
      The offer improved the accessibility and the utilization of medical services by
      SW in Bochum. A further improvement of services is urgently needed.

PMID- 27689226
TI  - [Hypoglossal nerve stimulation in patients with CPAP failure : Evolution of an
      alternative treatment for patients with obstructive sleep apnea].
AB  - Obstructive sleep apnea (OSA) is a common disease in western industrialized
      countries with increasing prevalence. Gold standard of therapy is nocturnal
      positive pressure ventilation by continuous positive airway pressure (CPAP). Due
      to complications and side effects of ventilation, therapy adherence is limited.
      Recently an alternative surgical treatment has become available for these
      patients, which uses established techniques to stimulate the hypoglossus nerve to
      open the upper airway during sleep. The aim of this work is to provide an
      overview of the history and current state of scientific knowledge of this therapy
      in the treatment of OSA. Currently, two systems are available on the market:
      respiratory-driven hypoglossal nerve stimulation (Inspire Medical Systems) and
      continuous hypoglossal nerve stimulation (ImThera Medical). For respiratory
      driven hypoglossal nerve stimulation, a solid body of evidence is available and
      the therapy has been investigated in numerous multicenter clinical studies with
      regard to safety and efficacy. Only a small number of publications is available
      for continuous hypoglossal nerve stimulation. At the end of the last century,
      promising clinical results were shown in the first patients treated with
      hypoglossal nerve stimulation. Consequent technological and scientific
      development of respiratory-driven hypoglossal nerve stimulation in recent years
      led to its implementation in today's clinical routine. This therapy significantly
      broadens the spectrum of therapies in the treatment of OSA, especially for
      patients with CPAP intolerance.

PMID- 27689227
TI  - [Endoscopic ear surgery - complement to microscopic ear surgery].
AB  - Wullstein, the founder of modern microscopic ear surgery, already used an oto
      endoscope intraoperatively. However, it is only after the recent development of
      modern video-endoscopy with high definition, 4-k, and 3-dimensional imaging that
      endoscopically guided surgery of the middle ear is gaining some importance. Key
      ventilation routes like the isthmus tympani and the epitympanic diaphragma can be
      visualized far better by using an endoscope rather than a microscope. Going
      through the external meatus surgery of middle ear pathologies is possible without
      external incision. This type of primary endoscopic ear surgery has to be
      distinguished from secondary endoscopic ear surgery, where standard microscopic
      ear surgery is supplemented by endoscopic surgery. Having to hold the endoscope
      in one hand, surgery has to be performed single-handed, which is awkward. In case
      of extensive bone removal or excessive bleeding the view through the endoscope
      lense is obscured, the endoscope therefore cannot fully substitute the use of the
      microscope. It is however an interesting adjunct to microscopic ear surgery.

PMID- 27689229
TI  - [Not Available].

PMID- 27689228
TI  - [Speech audiometry in expert assessment of hearing impairment].
AB  - In the assessment process of hearing impairment the medical expert has to verify
      its causality and to quantify its severity as hearing loss in percentage. Based
      on the determined hearing loss in percentage, the degree of impairment/disability
      or, in the case of work-related noise-induced hearing loss, the reduction in
      earning capacity is estimated. In Germany the guideline for the expert assessment
      of work-related noise-induced hearing loss is the Konigstein Guideline.
      Currently, the 5th edition from 2012 is used. Here, the hearing loss
      quantification depends mainly on the results of speech audiometry. Based on the
      Freiburg speech test, the hearing loss in percentage is determined using approved
      tables. For patients with a mild hearing loss, typically characterized by a high
      frequency hearing loss, tone audiometry results are consulted additionally.
      Speech-in-noise tests are available and are frequently used to measure the
      benefit of hearing systems. They allow for the detection of these patients'
      hearing impairment, which generally occurs in noisy environments. The first
      suggestions for a table to determine hearing loss in noise in percent are
      available. In experimental studies it was shown that tests in quiet, other than
      the Freiburg speech test, can be used and the same tables can be applied. In this
      article the current use of speech audiometry for expert assessment is presented,
      and options of using further developed speech test material are discussed.

PMID- 27689230
TI  - [Prostate carcinoma + swelling of the leg = lymphedema : Is the equation
      correct?]
AB  - Prostate carcinomas are often associated with lymphedemas of the leg following
      surgical treatment. Lymphedema is treated using complete decongestive therapy
      (CDT) with manual lymph drainage and compressive bandaging or stockings.
      Lymphedema resulting from a distinct iliac lymph node metastasis is a rare
      condition. A 73-year-old patient with a diagnosed prostate carcinoma presented
      with distinct swelling in the right leg. Iliac and leg vein thrombosis could not
      be ruled out. An ultrasound image revealed a large lesion surrounding the right
      iliac arteries. The patient was treated using percutaneous transluminal
      angioplasty and a stent was implanted in the right external iliac vein. This
      resulted in an almost complete regression of the swelling in the leg within a
      short period of time. While lymphedema can generally be established by clinical
      examination, this specific case demonstrates that an additional vascular
      examination is advisable in the context of an underlying malignant condition.

PMID- 27689231
TI  - [Not Available].

PMID- 27689221
TI  - Molecular modulators of the circadian clock: lessons from flies and mice.
AB  - Circadian timekeeping is a ubiquitous mechanism that enables organisms to
      maintain temporal coordination between internal biological processes and time of
      the local environment. The molecular basis of circadian rhythms lies in a set of
      transcription-translation feedback loops (TTFLs) that drives the rhythmic
      transcription of core clock genes, whose level and phase of expression serve as
      the marker of circadian time. However, it has become increasingly evident that
      additional regulatory mechanisms impinge upon the TTFLs to govern the properties
      and behavior of the circadian clock. Such mechanisms include changes in chromatin
      architecture, interactions with other transcription factor networks, post
      transcriptional control by RNA modifications, alternative splicing and microRNAs,
      and post-translational regulation of subcellular trafficking and protein
      degradation. In this review, we will summarize the current knowledge of circadian
      clock regulation-from transcriptional to post-translational-drawing from
      literature pertaining to the Drosophila and murine circadian systems.

PMID- 27689232
TI  - Scale insect larvae preserved in vertebrate coprolites (Le Quesnoy, France, Lower
      Eocene): paleoecological insights.
AB  - Coprolites of terrestrial vertebrates from the Sparnacian Le Quesnoy locality
      (Ypresian, Eocene, MP7, 53 Ma; Oise, France) were examined for possible parasitic
      helminth eggs. The extraction of the coprolite components was performed by a weak
      acetolyse and a slide mounting in glycerin. This long examination did not reveal
      paleoparasite remains, which may be explained through several arguments. However,
      some pollen grains, some enigmatic components, and two well-preserved first
      instar cochineal nymphs (Hemiptera: Sternorrhyncha: Coccoidea) were evidenced in
      coprolites. Identified as Coccidae, these larvae are the earliest stage of the
      scale insect development ever reported as fossil, revealing the specific
      environment of preservation that fossilized scats may provide. These
      observations, combined to the coprolites morphotype, enable to ascribe the fossil
      scats producer to a small herbivorous mammal present in the deposit (early
      perissodactyls or Plesiadapidae). Regarding the ecology of extant representatives
      of Coccidae, this mammal was a likely foliage consumer, and the abundant
      Juglandaceae and/or Tiliaceae from Le Quesnoy might have lived parasitized by
      scale insects. These Early Eocene parasites had an already well-established
      dissemination strategy, with prevalent minute first-instar larvae. The herein
      performed extraction technique appears well-suited for the study of carbonate
      coprolites and could certainly be useful for evidencing other kind of
      microorganisms (including internal parasites).

PMID- 27689234
TI  - Multimodal Imaging-Guided Antitumor Photothermal Therapy and Drug Delivery Using
      Bismuth Selenide Spherical Sponge.
AB  - Elaborately designed biocompatible nanoplatforms simultaneously having diverse
      therapeutic and imaging functions are highly desired for biomedical applications.
      Herein, a Bi2Se3 nanoagent with a special morphology as a nanoscale spherical
      sponge (NSS) has been fabricated and investigated in vitro and in vivo. The
      highly porous NSS exhibits strong, steady, and broad-band absorbance in the near
      infrared range as well as high efficiency and stability of photothermal
      conversion, resulting in high antitumor efficacy for photothermal therapy (PTT).
      Together with a high X-ray attenuation coefficient (218% that of the clinically
      used iopromide), the NSS shows excellent performance on triple-modal high
      contrast imaging, including X-ray-computed tomography, multispectral optoacoustic
      tomography, and infrared thermal imaging. Furthermore, the high surface area and
      porous structure impart the NSS a competent drug loading capability as high as
      600% of that on Bi2Se3 nanoplates, showing a bimodal pH/photothermal sensitive
      drug release and pronounced synergetic effects of thermo-chemotherapy with a
      tumor inhibition ratio even higher than that of PTT alone (~94.4% vs ~66.0%).
      Meanwhile, the NSS is highly biocompatible with rather low in vitro/in vivo
      toxicity and high stability, at variance with easily oxidized Bi2Se3 nanoagents
      reported previously. Such biocompatible single-component theranostic nanoagents
      produced by a facile synthesis and highly integrated multimodal imaging and
      multiple therapeutic functions may have substantial potentials for clinical
      antitumor applications. This highly porous nanostructure with a large fraction of
      void space may allow versatile use of the NSS, for example, in catalysis, gas
      sensing, and energy storage, in addition to accommodating drugs and other
      biomolecules.

PMID- 27689235
TI  - One-Step Synthesis of Water-Dispersible and Biocompatible Silicon Nanoparticles
      for Selective Heparin Sensing and Cell Imaging.
AB  - A sensitive and selective fluorescence "turn-off" sensor to detect heparin using
      water-soluble silicon nanoparticles (Si NPs) was developed for the first time.
      The Si NPs were synthesized by a simple one-step procedure, which did not need
      high-temperature and complex modification. The as-prepared Si NPs featured strong
      fluorescence, favorable biocompatibility, and robust photo- and pH stability.
      Significantly, the Si NPs were induced to assemble or aggregate via hydrogen
      bonding, which resulted in the fluorescence of Si NPs quenched. Under the
      optimized conditions, the linear range was obtained from 0.02 to 2.0 MUg/mL, with
      a limit of detection of 18 ng/mL (equal to 0.004 U/mL). It was lower than the
      proper therapeutic level of heparin during cardiovascular surgery and long-term
      therapy. This proposed method was relatively free of interference from heparin
      analogues, which commonly existed in heparin samples and could possibly affect
      heparin detection. Moreover, it did not need to introduce any control medium. As
      expected, the method was successfully applied to detect heparin in human serum
      samples with satisfactory recovery ranging from 98.8 to 102.5%. The Si NPs were
      superbly suitable for cell imaging owing to the negligible cytotoxicity and
      excellent biocompatibility.

PMID- 27689233
TI  - An interpretative phenomenological analysis (IPA) of coercion towards community
      dwelling older adults with dementia: findings from Mysore studies of natal
      effects on ageing and health (MYNAH).
AB  - PURPOSE: Limited availability of specialist services places a considerable burden
      on caregivers of Persons with Dementia (PwD) in Low- and Middle-Income Countries
      (LMICs). There are limited qualitative data on coercive behavior towards PwD in
      an LMIC setting. AIM: The aim of this study was to find relevant themes of the
      lived experience of relatives as caregivers for PwD in view of their use of
      coercive measures in community setting in South India. METHOD: Primary caregivers
      (n = 13) of PwDs from the Mysore study of Natal effects on Ageing and Health
      (MYNAH) in South India were interviewed to explore the nature and impact of
      coercion towards community dwelling older adults with dementia. The narrative
      data were coded using an Interpretative Phenomenological Analysis (IPA) approach
      for thematic analysis and theory formation. RESULTS: Caregivers reported feeling
      physical and emotional burn-out, a lack of respite care, an absence of shared
      caregiving arrangements, limited knowledge of dementia, and a complete lack of
      community support services. They reported restrictions on their lives through not
      being able take employment, a poor social life, reduced income and job
      opportunities, and restricted movement that impacted on their physical and
      emotional well-being. Inappropriate use of sedatives, seclusion and environmental
      restraint, and restricted dietary intake, access to finances and participation in
      social events, was commonly reported methods of coercion used by caregivers
      towards PwD. Reasons given by caregivers for employing these coercive measures
      included safeguarding of the PwD and for the management of behavioral problems
      and physical health. CONCLUSION: There is an urgent need for training health and
      social care professionals to better understand the use of coercive measures and
      their impact on persons with dementia in India. It is feasible to conduct
      qualitative research using IPA in South India.

PMID- 27689236
TI  - Microfiber Masses Recovered from Conventional Machine Washing of New or Aged
      Garments.
AB  - Synthetic textiles can shed numerous microfibers during conventional washing, but
      evaluating environmental consequences as well as source-control strategies
      requires understanding mass releases. Polyester apparel accounts for a large
      proportion of the polyester market, and synthetic jackets represent the broadest
      range in apparel construction, allowing for potential changes in manufacturing as
      a mitigation measure to reduce microfiber release during laundering. Here,
      detergent-free washing experiments were conducted and replicated in both front-
      and top-load conventional home machines for five new and mechanically aged
      jackets or sweaters: four from one name-brand clothing manufacturer (three
      majority polyester fleece, and one nylon shell with nonwoven polyester
      insulation) and one off-brand (100% polyester fleece). Wash water was filtered to
      recover two size fractions (>333 MUm and between 20 and 333 MUm); filters were
      then imaged, and microfiber masses were calculated. Across all treatments, the
      recovered microfiber mass per garment ranged from approximately 0 to 2 g, or
      exceeding 0.3% of the unwashed garment mass. Microfiber masses from top-load
      machines were approximately 7 times those from front-load machines; garments
      mechanically aged via a 24 h continuous wash had increased mass release under the
      same wash protocol as new garments. When published wastewater treatment plant
      influent characterization and microfiber removal studies are considered, washing
      synthetic jackets or sweaters as per this study would account for most
      microfibers entering the environment.

PMID- 27689238
TI  - Oxidative Coupling of (-)-Sclareol and Related Diols Leading to Oxepane
      Terpenoids.
AB  - Treatment of (-)-sclareol and related compounds with lead tetraacetate affords
      tetracyclic compounds bearing a 2,8-dioxabicyclo[5.2.0]nonane moiety with
      complete regio- and stereoselectivity. This process, which is also applicable to
      1,5-diols with a similar substitution pattern, facilitates the development of
      efficient syntheses toward oxepane terpenoids, such as aplysistatin derivatives.

PMID- 27689237
TI  - Strong Coupling of Localized Surface Plasmons to Excitons in Light-Harvesting
      Complexes.
AB  - Gold nanostructure arrays exhibit surface plasmon resonances that split after
      attaching light harvesting complexes 1 and 2 (LH1 and LH2) from purple bacteria.
      The splitting is attributed to strong coupling between the localized surface
      plasmon resonances and excitons in the light-harvesting complexes. Wild-type and
      mutant LH1 and LH2 from Rhodobacter sphaeroides containing different carotenoids
      yield different splitting energies, demonstrating that the coupling mechanism is
      sensitive to the electronic states in the light harvesting complexes. Plasmon
      exciton coupling models reveal different coupling strengths depending on the
      molecular organization and the protein coverage, consistent with strong coupling.
      Strong coupling was also observed for self-assembling polypeptide maquettes that
      contain only chlorins. However, it is not observed for monolayers of
      bacteriochlorophyll, indicating that strong plasmon-exciton coupling is sensitive
      to the specific presentation of the pigment molecules.

PMID- 27689239
TI  - Treatment options for hypertension in pregnancy and puerperium.
AB  - INTRODUCTION: Hypertensive disorders have become increasingly prevalent and
      complicate an increasing number of pregnancies. Therefore it is essential that
      the medications used to treat these disorders be well understood. Furthermore the
      management is complicated by special consideration needed for the physiologic
      changes of pregnancy as well as the consideration for possible adverse fetal
      effects. Areas covered: We performed a review of the scientific literature of
      medications used to treat hypertensive disorders in pregnancy. We reviewed the
      guidelines used by different societies all over the world. We also discussed the
      pharmacodynamics, pharmacokinetics and possible adverse effects relating to the
      antihypertensive medications. Finally, we discussed the long-term maternal
      implications of these diseases. Expert opinion: Overall, we encourage a step-wise
      approach to treating hypertensive disorders of pregnancy. While making sure to
      max out the use of one medications prior to shifting to another. Also, it is
      imperative not to be aggressive with treatment due to risk of compromising utero
      placental blood flow. There is research currently involving biomarkers, nano
      medicine and the placenta project with hopes of developing new targeted
      medications with a good fetal safety profile.

PMID- 27689240
TI  - Enhanced Electroreductive Removal of Bromate by a Supported Pd-In Bimetallic
      Catalyst: Kinetics and Mechanism Investigation.
AB  - In this work, the electroreductive removal of bromate by a Pd1-In4/Al2O3 catalyst
      in a three-dimensional electrochemical reactor was investigated. A total of 96.4%
      of bromate could be efficiently reduced and completely converted into bromide
      within 30 min under optimized conditions. On the basis of the characterization
      results and kinetics analysis, a synergistic effect of Pd and In was observed,
      and Pd1-In4/Al2O3 had the highest reaction rate constant of 0.1275 min-1 (vs
      0.0413, 0.0328, and 0.0253 min-1 for In/Al2O3, Pd/Al2O3, and Al2O3). The results
      of electron spin resonance and scavenger experiments confirmed that both direct
      electron transfer and indirect reduction by atomic H* were involved in the
      bromate removal process, while the direct reduction played a more important role.
      Moreover, the introduction of In could increase the zeta potential of Pd1
      In4/Al2O3, facilitating bromate adsorption and its subsequent reduction on the
      catalyst. Finally, a reaction mechanism for bromate reduction by Pd1-In4/Al2O3
      was proposed based on all the experimental results.

PMID- 27689241
TI  - QTAIM-Based Characteristic Group Infrared Intensities of Amino Acids and Their
      Transference to Peptides.
AB  - Dynamic atomic contributions (DACs) to the infrared intensities of 14 amino acids
      have been transferred to three peptide molecules, glycylglycine, trialanine, and
      the melanocyte-inhibiting factor MIF-1, to estimate the infrared intensities of
      the most strategic peptide bands. The DACs of the amino acids and infrared
      intensities of the peptides were determined at the DFT B3LYP/6-311+(d,p) level.
      The Quantum Theory of Atoms In Molecules (QTAIM) Charge-Charge Transfer-Dipolar
      Polarization (CCTDP) model at this Density Functional Theory (DFT) level was used
      to classify the O-H, NH2, N-H, and C?O stretching as well as the NH2 bending
      characteristic groups for use in the transference procedure. Contrary to the
      frequencies, the intensities within these groups can have very diverse values,
      although their electronic structure changes upon vibration have predictable QTAIM
      behaviors for each group. Compared to the DFT calculated values, the two
      transferred O-H stretching intensities of the peptides are estimated with a root
      mean-square (rms) error of 19.1 km mol-1. Six NH2 symmetric and antisymmetric
      stretching intensities were determined with a 9.9 km mol-1 error. The eight
      estimated C?O stretching bands have a rms error of 78.0 km mol-1 or 23.6% of the
      average DFT peptide C?O intensity of 328.4 km mol-1. The proposed procedure is
      applicable to experimental infrared intensities if a calibration set of molecules
      with known atomic polar tensors and normal coordinate transformations is
      available.

PMID- 27689242
TI  - Latent variable modeling to analyze the effects of process parameters on the
      dissolution of paracetamol tablet.
AB  - The dissolution is one of the critical quality attributes (CQAs) of oral solid
      dosage forms because it relates to the absorption of drug. In this paper, the
      influence of raw materials, granules and process parameters on the dissolution of
      paracetamol tablet was analyzed using latent variable modeling methods. The
      variability in raw materials and granules was understood based on the principle
      component analysis (PCA), respectively. A multi-block partial least squares
      (MBPLS) model was used to determine the critical factors affecting the
      dissolution. The results showed that the binder amount, the post granulation
      time, the API content in granule, the fill depth and the punch tip separation
      distance were the critical factors with variable importance in the projection
      (VIP) values larger than 1. The importance of each unit of the whole process was
      also ranked using the block importance in the projection (BIP) index. It was
      concluded that latent variable models (LVMs) were very useful tools to extract
      information from the available data and improve the understanding on dissolution
      behavior of paracetamol tablet. The obtained LVMs were also helpful to propose
      the process design space and to design control strategies in the further
      research.

PMID- 27689243
TI  - Transcranial motor evoked potential waveform changes in corrective fusion for
      adolescent idiopathic scoliosis.
AB  - OBJECTIVE Corrective surgery for spinal deformities can lead to neurological
      complications. Several reports have described spinal cord monitoring in surgery
      for spinal deformity, but only a few have included patients younger than 20 years
      with adolescent idiopathic scoliosis (AIS). The goal of this study was to
      evaluate the characteristics of cases with intraoperative transcranial motor
      evoked potential (Tc-MEP) waveform deterioration during posterior corrective
      fusion for AIS. METHODS A prospective database was reviewed, comprising 68
      patients with AIS who were treated with posterior corrective fusion in a
      prospective database. A total of 864 muscles in the lower extremities were chosen
      for monitoring, and acceptable baseline responses were obtained from 819 muscles
      (95%). Intraoperative Tc-MEP waveform deterioration was defined as a decrease in
      intraoperative amplitude of >= 70% of the control waveform. Age, Cobb angle,
      flexibility, operative time, estimated blood loss (EBL), intraoperative body
      temperature, blood pressure, number of levels fused, and correction rate were
      examined in patients with and without waveform deterioration. RESULTS The
      patients (3 males and 65 females) had an average age of 14.4 years (range 11-19
      years). The mean Cobb angles before and after surgery were 52.9 degrees  and 11.9
      degrees , respectively, giving a correction rate of 77.4%. Fourteen patients
      (20%) exhibited an intraoperative waveform change, and these occurred during
      incision (14%), after screw fixation (7%), during the rotation maneuver (64%),
      during placement of the second rod after the rotation maneuver (7%), and after
      intervertebral compression (7%). Most waveform changes recovered after decreased
      correction or rest. No patient had a motor deficit postoperatively. In
      multivariate analysis, EBL (OR 1.001, p = 0.085) and number of levels fused (OR
      1.535, p = 0.045) were associated with waveform deterioration. CONCLUSIONS
      Waveform deterioration commonly occurred during rotation maneuvers and more
      frequently in patients with a larger preoperative Cobb angle. The significant
      relationships of EBL and number of levels fused with waveform deterioration
      suggest that these surgical invasions may be involved in waveform deterioration.

PMID- 27689244
TI  - Clinical predictors of vestibulo-ocular dysfunction in pediatric sports-related
      concussion.
AB  - OBJECTIVE There were 2 objectives of this study. The first objective was to
      identify clinical variables associated with vestibulo-ocular dysfunction (VOD)
      detected at initial consultation among pediatric patients with acute sports
      related concussion (SRC) and postconcussion syndrome (PCS). The second objective
      was to reexamine the prevalence of VOD in this clinical cohort and evaluate the
      effect of VOD on length of recovery and the development of PCS. METHODS A
      retrospective review was conducted for all patients with acute SRC and PCS who
      were evaluated at a pediatric multidisciplinary concussion program from September
      2013 to May 2015. Acute SRS was defined as presenting < 30 days postinjury, and
      PCS was defined according to the International Classification of Diseases, 10th
      Revision criteria and included being symptomatic 30 days or longer postinjury.
      The initial assessment included clinical history and physical examination
      performed by 1 neurosurgeon. Patients were assessed for VOD, defined as the
      presence of more than 1 subjective vestibular and oculomotor complaint
      (dizziness, diplopia, blurred vision, etc.) and more than 1 objective physical
      examination finding (abnormal near point of convergence, smooth pursuits,
      saccades, or vestibulo-ocular reflex testing). Poisson regression analysis was
      used to identify factors that increased the risk of VOD at initial presentation
      and the development of PCS. RESULTS Three hundred ninety-nine children, including
      306 patients with acute SRC and 93 with PCS, were included. Of these patients,
      30.1% of those with acute SRC (65.0% male, mean age 13.9 years) and 43.0% of
      those with PCS (41.9% male, mean age 15.4 years) met the criteria for VOD at
      initial consultation. Independent predictors of VOD at initial consultation
      included female sex, preinjury history of depression, posttraumatic amnesia, and
      presence of dizziness, blurred vision, or difficulty focusing at the time of
      injury. Independent predictors of PCS among patients with acute SRC included the
      presence of VOD at initial consultation, preinjury history of depression, and
      posttraumatic amnesia at the time of injury. CONCLUSIONS This study identified
      important potential risk factors for the development of VOD following pediatric
      SRC. These results provide confirmatory evidence that VOD at initial consultation
      is associated with prolonged recovery and is an independent predictor for the
      development of PCS. Future studies examining clinical prediction rules in
      pediatric concussion should include VOD. Additional research is needed to
      elucidate the natural history of VOD following SRC and establish evidence-based
      indications for targeted vestibular rehabilitation.

PMID- 27689245
TI  - Vessel-preserving stent-assisted coil embolization of an extracranial internal
      carotid artery pseudoaneurysm that developed after tonsillectomy in a pediatric
      patient: initial case report.
AB  - Although there have been reports of carotid artery pseudoaneurysm formation after
      adenoidectomy and/or tonsillectomy secondary to iatrogenic injury, there are no
      case reports of successful endovascular reconstruction of the injured artery in
      the pediatric population. In most pediatric cases, the internal carotid artery
      (ICA) is sacrificed. The authors report on a 6-year-old girl who presented with
      odynophagia, left-sided Horner's syndrome, hematemesis, and severe anemia 6
      months after a tonsillectomy. On examination she was found to have a pulsatile
      mass along the left posterior lateral oropharynx, and imaging demonstrated a
      dissection of the extracranial left ICA and an associated pseudoaneurysm. The
      lesion was managed endovascularly with stent-assisted coil embolization and ICA
      reconstruction. The child had a somewhat complicated postoperative course,
      requiring additional coil embolization for treatment of a minor recurrence of the
      pseudoaneurysm at 5 months after the initial treatment and then presenting with
      extrusion of a portion of the coil mass into the oropharyngeal cavity a year
      later. She underwent surgical removal of the extruded coils and repair of the
      defect and has since been free of symptoms or signs of recurrence. The authors
      conclude that this strategy definitively protected the patient against an oral
      exsanguination or aspiration event secondary to aneurysm rupture and reduced her
      risk of stroke by preserving vessel patency and caliber. Moreover, they note that
      covered stent reconstruction surrenders endovascular access and cannot
      immediately provide these benefits.

PMID- 27689246
TI  - Hemisacrectomy with preservation of the contralateral sacral nerve roots and
      sacroiliac joint for pelvic neurofibrosarcoma in a 7-year-old child: case report
      with 2-year follow-up.
AB  - Neurofibrosarcoma is rare in the pediatric age group. A malignant tumor of the
      sacrum presents significant challenges, especially if the goals are to resect
      with wide and clean surgical margins and to achieve acceptable functional
      outcomes. The authors report a case of this rare tumor affecting the sacrum and
      sacral nerve roots of a 7-year-old girl and review the role of total
      hemisacrectomy sparing the contralateral sacral nerve roots and lumbopelvic
      reconstruction in the treatment of this disease. This patient is, to the best of
      the authors' knowledge, the youngest to be treated in this manner.

PMID- 27689248
TI  - Trends and Predictors of Limb Tourniquet Use by Civilian Emergency Medical
      Services in the United States.
AB  - BACKGROUND: Tourniquet use by Emergency Medical Services (EMS) can be life saving
      for severely injured patients. The adoption of this intervention is not well
      described in civilian settings. This study describes patterns and trends of
      tourniquet use by civilian EMS and identifies predictors of such use. METHODS: A
      retrospective study of four consecutive releases of the U.S. National Emergency
      Medical Services Information System (NEMSIS) public research dataset (2011-14)
      was conducted. Descriptive analysis was performed to compare two groups of EMS
      activations for injuries with or without tourniquet application. This was
      followed by multivariate logistic regression to identify predictors of tourniquet
      use. RESULTS: A total of 2,048 tourniquet applications were documented among all
      EMS activations for injured patients (N = 10,366,537) yielding a prevalence of
      0.2 per 1,000 EMS activations. Tourniquets were mainly applied in young (mean age
      44.0 +/- 21.1 years) male patients (76.5%) in urban and suburban EMS activations
      (86.4%) and by advanced life support (ALS) EMS services (81.6%). Most common
      complaints reported by dispatch for EMS activations with tourniquet use were
      Traumatic injury (25.3%), Hemorrhage/laceration (23.5%), and Traffic accident
      (16.8%) with injuries mainly related to Stabbing/Accidental cutting (20.3%),
      Falls (17.1%), and Motor vehicle traffic accident (11.5%). Upper extremity
      injuries (39.6%) were more common than Lower extremity injuries (27.3%). The
      providers' primary impression was predominantly Traumatic injury (92.8%), and
      patients' primary symptoms were mainly Bleeding (50.4%) and Wound (28.7%). All
      prehospital time intervals except on-scene time interval were significantly
      shorter in the group with tourniquets compared to the group without tourniquets
      (p < 0.05). Reported prevalence of tourniquet use by EMS (per 1,000 EMS injury
      activations) increased from 2011 to 2012 then stabilized over the following years
      (2012-14). Significant predictors of tourniquet use reported by the provider were
      identified and included demographic characteristics, EMS agency type, specific
      complaints, injury cause, injury anatomic location, chief complaint organ system,
      and primary symptom. CONCLUSION: Reported tourniquet use by EMS for injured
      patients in the U.S. is low. Increasing adoption mainly by urban services was
      noted. Predictors for tourniquet use in civilian trauma were identified.
      Establishing the effectiveness of this intervention by comparing patient outcomes
      is needed. Key words: emergency medical services; prehospital; tourniquet;
      injury; NEMSIS; hemorrhage.

PMID- 27689249
TI  - Predominance of Streptococcus suis ST1 and ST7 in human cases in China, and
      detection of a novel sequence type, ST658.

PMID- 27689250
TI  - Subclinical Thyroid Dysfunction and the Risk of Cognitive Decline: a Meta
      Analysis of Prospective Cohort Studies.
AB  - CONTEXT: Although both overt hyper- and hypothyroidism are known to lead to
      cognitive impairment, data on the association between subclinical thyroid
      dysfunction and cognitive function are conflicting. OBJECTIVE: This study sought
      to determine the risk of dementia and cognitive decline associated with
      subclinical thyroid dysfunction among prospective cohorts. DATA SOURCES: We
      searched in MEDLINE and EMBASE from inception until November 2014. STUDY
      SELECTION: Two physicians identified prospective cohorts that assessed thyroid
      function and cognitive outcomes (dementia; Mini-Mental State Examination [MMSE]).
      DATA EXTRACTION: Data were extracted by one reviewer following standardized
      protocols and verified by a second reviewer. The primary outcome was dementia and
      decline in cognitive function was the secondary outcome. DATA SYNTHESIS: Eleven
      prospective cohorts followed 16,805 participants during a median followup of 44.4
      months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism
      (SHyper) (n = 6410), six in subclinical hypothyroidism (SHypo) (n = 7401). Five
      studies analyzed MMSE decline in SHyper (n = 7895), seven in SHypo (n = 8960). In
      random-effects models, the pooled adjusted risk ratio for dementia in SHyper was
      1.67 (95% confidence interval, 1.04; 2.69) and 1.14 (95% confidence interval,
      0.84; 1.55) in SHypo vs euthyroidism, both without evidence of significant
      heterogeneity (I2 = 0.0%). The pooled mean MMSE decline from baseline to followup
      (mean 32 mo) did not significantly differ between SHyper or SHypo vs
      euthyroidism. CONCLUSIONS: SHyper might be associated with an elevated risk for
      dementia, whereas SHypo is not, and both conditions are not associated with
      faster decline in MMSE over time. Available data are limited, and additional
      large, high-quality studies are needed.

PMID- 27689251
TI  - miR-146a, miR-155, miR-370, and miR-708 Are CFTR-Dependent, Predicted FOXO1
      Regulators and Change at Onset of CFRDs.
AB  - CONTEXT: Cystic fibrosis-related diabetes (CFRD) is the most frequent and severe
      co-morbidity in cystic fibrosis (CF). Presentation and severity are quite
      variable. OBJECTIVE: To investigate changes in microRNAs (miRNAs) due to CF
      transmembrane conductance regulator malfunctioning in vitro, to study the
      circulating levels of selected miRNAs in serum samples from patients, and to
      assess their relationships in different age groups with genotype, glucose
      tolerance state, and at onset of CFRD. Design/Setting/Patients/Interventions:
      Transcriptional profiling of all known miRNAs in CFBE41o- cells, in their normal
      counterparts (16HBE14o- cells), and in IB3 cells was performed. A set of miRNAs
      was differentially expressed in the CF cells. By in silico analysis, four miRNAs
      (miR-146a, miR-155, miR-370, and miR-708) were selected as potential regulators
      of the FOXO1 gene. Seventy-four CF patients and 50 healthy subjects whose glucose
      tolerance was characterized by an oral glucose tolerance test were enrolled in
      the study, and the identified miRNAs were quantified in serum by quantitative RT
      PCR. Main Outcome Measurements/Results: A total of 111 miRNAs were differentially
      expressed in the two CF cell lines. miR-155, miR-370, and miR-708 were up
      regulated and miR-146a was down-regulated in vitro, whereas in vivo, miR-146a,
      miR-155, and miR-370 were up-regulated, and miR-708 was down-regulated. These
      changes showed relationships with genotype, glucose tolerance state, and onset of
      CFRD. CONCLUSIONS: The data showed significant changes in miRNAs dependent on
      genotype and glucose tolerance state in CF patients and highlighted some miRNAs
      of importance in CFRD at onset. miRNAs could explain some of the variability
      observed in CF.

PMID- 27689252
TI  - Clinical, Sonographic, and Pathological Characteristics of RAS-Positive Versus
      BRAF-Positive Thyroid Carcinoma.
AB  - CONTEXT: Mutations in the BRAF and RAS oncogenes are responsible for most well
      differentiated thyroid cancer. Yet, our clinical understanding of how BRAF
      positive and RAS-positive thyroid cancers differ is incomplete. OBJECTIVE: We
      correlated clinical, radiographic, and pathological findings from patients with
      thyroid cancer harboring a BRAF or RAS mutation. DESIGN: Prospective cohort
      study. SETTING: Academic, tertiary care hospital. PATIENTS: A total of 101
      consecutive patients with well-differentiated thyroid cancer. MAIN OUTCOME
      MEASURE: We compared the clinical, sonographic, and pathological characteristics
      of patients with BRAF-positive cancer to those with RAS-positive cancer. RESULTS:
      Of 101 patients harboring these mutations, 71 were BRAF-positive, whereas 30 were
      RAS-positive. Upon sonographic evaluation, RAS-positive nodules were
      significantly larger (P = .04), although BRAF-positive nodules were more likely
      to harbor concerning sonographic characteristics (hypoechogenicity [P < .001];
      irregular margins [P = .04]). Cytologically, 70% of BRAF-positive nodules were
      classified positive for PTC, whereas 87% of RAS-positive nodules were
      indeterminate (P < .001). Histologically, 96% of RAS-positive PTC malignancies
      were follicular variants of PTC, whereas 70% of BRAF-positive malignancies were
      classical variants of PTC. BRAF-positive malignancies were more likely to
      demonstrate extrathyroidal extension (P = .003), lymphovascular invasion (P =
      .02), and lymph node metastasis (P < .001). CONCLUSIONS: BRAF-positive malignant
      nodules most often demonstrate worrisome sonographic features and are frequently
      associated with positive or suspicious Bethesda cytology. In contrast, RAS
      positive malignancy most often demonstrates indolent sonographic features and
      more commonly associates with lower risk, "indeterminate" cytology. Because BRAF
      and RAS mutations are the most common molecular perturbations associated with
      well-differentiated thyroid cancer, these findings may assist with improved
      preoperative risk assessment by suggesting the likely molecular profile of a
      thyroid cancer, even when postsurgical molecular analysis is unavailable.

PMID- 27689254
TI  - Doctors' recognition and management of melanoma patients' risk: An Australian
      population-based study.
AB  - BACKGROUND: Guidelines recommend that health professionals identify and manage
      individuals at high risk of developing melanoma, but there is limited population
      based evidence demonstrating real-world practices. OBJECTIVE: A population-based,
      observational study was conducted in the state of New South Wales, Australia to
      determine doctors' knowledge of melanoma patients' risk and to identify factors
      associated with better identification and clinical management. METHODS: Data were
      analysed for 1889 patients with invasive, localised melanoma in the Melanoma
      Patterns of Care study. This study collected data on all melanoma diagnoses
      notified to the state's cancer registry during a 12-month period from 2006 to
      2007, as well as questionnaire data from the doctors involved in their care.
      RESULTS: Three-quarters (74%) of patients had doctors who were aware of their
      risk factor status with respect to personal and family history of melanoma and
      the presence of many moles. Doctors working in general practice, skin cancer
      clinics and dermatology settings had better knowledge of patients' risk factors
      than plastic surgeons. Doctors were 15% more likely to know the family history of
      younger melanoma patients (<40years) than of those >=80 years (95% confidence
      interval 4-26%). Early detection-related follow-up advice was more likely to be
      given to younger patients, by doctors aware of their patients' risk status, by
      doctors practising in plastic surgery, dermatology and skin cancer clinic
      settings, and by female doctors. CONCLUSION: Both patient-related and doctor
      related factors were associated with doctors' recognition and management of
      melanoma patients' risk and could be the focus of strategies for improving care.

PMID- 27689255
TI  - Direct Measurement of the Density Matrix of a Quantum System.
AB  - One drawback of conventional quantum state tomography is that it does not readily
      provide access to single density matrix elements since it requires a global
      reconstruction. Here, we experimentally demonstrate a scheme that can be used to
      directly measure individual density matrix elements of general quantum states.
      The scheme relies on measuring a sequence of three observables, each
      complementary to the last. The first two measurements are made weak to minimize
      the disturbance they cause to the state, while the final measurement is strong.
      We perform this joint measurement on polarized photons in pure and mixed states
      to directly measure their density matrix. The weak measurements are achieved
      using two walk-off crystals, each inducing a polarization-dependent spatial shift
      that couples the spatial and polarization degrees of freedom of the photons. This
      direct measurement method provides an operational meaning to the density matrix
      and promises to be especially useful for large dimensional states.

PMID- 27689253
TI  - Role of Cytokine Gene Score in Risk Prediction of Premature Coronary Artery
      Disease.
AB  - AIMS: Pro- and anti-inflammatory cytokines play a significant role in early
      atherosclerosis. Linkage disequilibrium patterns differ between ethnic groups
      pointing toward the need to develop population-specific gene risk scores. Our
      objective was to investigate the role of a cytokine gene score in the risk
      prediction of premature coronary artery disease (PCAD). METHODS: A case-control
      study was performed at the National University of Sciences and Technology (NUST)
      in collaboration with the Cardiovascular Genetics Institute, University College
      London, United Kingdom. Three hundred forty subjects with >70% stenosis in at
      least one coronary vessel on angiography were labeled as PCAD cases and compared
      with 310 angio-negative controls. Genotyping of the rs187238 (interleukin [IL]
      18), rs1800795 (IL-6), rs1800629 (tumor necrosis factor [TNF]-alpha), rs1800871
      (IL-10), and rs1946519 (IL-18) SNPs was performed using KASPar and TaqMan assays.
      RESULTS: The odds ratio for cytokine gene score was significantly higher for PCAD
      (p = 0.025) when adjusted for age, sex, and ethnicity. There was a highly
      significant difference in gene risk allele frequency between Pakistanis and
      Caucasians (Northwick Park Heart Study II [NPHSII]) for rs187238 (IL-18),
      rs1800795 (IL-6), rs1800629 (TNF-alpha), and rs1800871 (IL-10) (p < 0.01).
      CONCLUSIONS: A cytokine gene score has significant discriminatory ability and
      potential in the risk prediction of PCAD. Cytokine gene risk allele frequencies
      differ significantly between Pakistanis and Caucasians supporting the need to
      develop population-specific gene scores.

PMID- 27689256
TI  - Accessing Many-Body Localized States through the Generalized Gibbs Ensemble.
AB  - We show how the thermodynamic properties of large many-body localized systems can
      be studied using quantum Monte Carlo simulations. We devise a heuristic way of
      constructing local integrals of motion of high quality, which are added to the
      Hamiltonian in conjunction with Lagrange multipliers. The ground state simulation
      of the shifted Hamiltonian corresponds to a high-energy state of the original
      Hamiltonian in the case of exactly known local integrals of motion. The
      inevitable mixing between eigenstates as a consequence of nonperfect integrals of
      motion is weak enough such that the characteristics of many-body localized
      systems are not averaged out, unlike the standard ensembles of statistical
      mechanics. Our method paves the way to study higher dimensions and indicates that
      a fully many-body localized phase in 2D, where (nearly) all eigenstates are
      localized, is likely to exist.

PMID- 27689257
TI  - Noise Threshold and Resource Cost of Fault-Tolerant Quantum Computing with
      Majorana Fermions in Hybrid Systems.
AB  - Fault-tolerant quantum computing in systems composed of both Majorana fermions
      and topologically unprotected quantum systems, e.g., superconducting circuits or
      quantum dots, is studied in this Letter. Errors caused by topologically
      unprotected quantum systems need to be corrected with error-correction schemes,
      for instance, the surface code. We find that the error-correction performance of
      such a hybrid topological quantum computer is not superior to a normal quantum
      computer unless the topological charge of Majorana fermions is insusceptible to
      noise. If errors changing the topological charge are rare, the fault-tolerance
      threshold is much higher than the threshold of a normal quantum computer and a
      surface-code logical qubit could be encoded in only tens of topological qubits
      instead of about 1,000 normal qubits.

PMID- 27689258
TI  - Quasiprobability Representations of Quantum Mechanics with Minimal Negativity.
AB  - Quasiprobability representations, such as the Wigner function, play an important
      role in various research areas. The inevitable appearance of negativity in such
      representations is often regarded as a signature of nonclassicality, which has
      profound implications for quantum computation. However, little is known about the
      minimal negativity that is necessary in general quasiprobability representations.
      Here we focus on a natural class of quasiprobability representations that is
      distinguished by simplicity and economy. We introduce three measures of
      negativity concerning the representations of quantum states, unitary
      transformations, and quantum channels, respectively. Quite surprisingly, all
      three measures lead to the same representations with minimal negativity, which
      are in one-to-one correspondence with the elusive symmetric informationally
      complete measurements. In addition, most representations with minimal negativity
      are automatically covariant with respect to the Heisenberg-Weyl groups.
      Furthermore, our study reveals an interesting tradeoff between negativity and
      symmetry in quasiprobability representations.

PMID- 27689259
TI  - Grover Search and the No-Signaling Principle.
AB  - Two of the key properties of quantum physics are the no-signaling principle and
      the Grover search lower bound. That is, despite admitting stronger-than-classical
      correlations, quantum mechanics does not imply superluminal signaling, and
      despite a form of exponential parallelism, quantum mechanics does not imply
      polynomial-time brute force solution of NP-complete problems. Here, we
      investigate the degree to which these two properties are connected. We examine
      four classes of deviations from quantum mechanics, for which we draw inspiration
      from the literature on the black hole information paradox. We show that in these
      models, the physical resources required to send a superluminal signal scale
      polynomially with the resources needed to speed up Grover's algorithm. Hence the
      no-signaling principle is equivalent to the inability to solve NP-hard problems
      efficiently by brute force within the classes of theories analyzed.

PMID- 27689260
TI  - Observation of Noise Correlated by the Hawking Effect in a Water Tank.
AB  - We measured the power spectrum and two-point correlation function for the
      randomly fluctuating free surface on the downstream side of a stationary flow
      with a maximum Froude number F_{max}~0.85 reached above a localized obstacle. On
      such a flow the scattering of incident long wavelength modes is analogous to that
      responsible for black hole radiation (the Hawking effect). Our measurements of
      the noise show a clear correlation between pairs of modes of opposite energies.
      We also measure the scattering coefficients by applying the same analysis of
      correlations to waves produced by a wave maker.

PMID- 27689261
TI  - Detectability of Light Dark Matter with Superfluid Helium.
AB  - We show that a two-excitation process in superfluid helium, combined with
      sensitivity to meV energy depositions, can probe dark matter down to the ~keV
      warm dark matter mass limit. This mass reach is 3 orders of magnitude below what
      can be probed with ordinary nuclear recoils in helium at the same energy
      resolution. For dark matter lighter than ~100  keV, the kinematics of the process
      requires the two athermal excitations to have nearly equal and opposite momentum,
      potentially providing a built-in coincidence mechanism for controlling
      backgrounds.

PMID- 27689263
TI  - Classically Stable Nonsingular Cosmological Bounces.
AB  - One of the fundamental questions of theoretical cosmology is whether the Universe
      can undergo a nonsingular bounce, i.e., smoothly transit from a period of
      contraction to a period of expansion through violation of the null energy
      condition (NEC) at energies well below the Planck scale and at finite values of
      the scale factor such that the entire evolution remains classical. A common claim
      has been that a nonsingular bounce either leads to ghost or gradient
      instabilities or a cosmological singularity. In this Letter, we consider a well
      motivated class of theories based on the cubic Galileon action and present a
      procedure for explicitly constructing examples of a nonsingular cosmological
      bounce without encountering any pathologies and maintaining a subluminal sound
      speed for comoving curvature modes throughout the NEC violating phase. We also
      discuss the relation between our procedure and earlier work.

PMID- 27689264
TI  - Matrix Product Approximations to Multipoint Functions in Two-Dimensional
      Conformal Field Theory.
AB  - Matrix product states (MPSs) illustrate the suitability of tensor networks for
      the description of interacting many-body systems: ground states of gapped 1D
      systems are approximable by MPSs, as shown by Hastings [M. B. Hastings, J. Stat.
      Mech. (2007) P08024]. By contrast, whether MPSs and more general tensor networks
      can accurately reproduce correlations in critical quantum systems or quantum
      field theories has not been established rigorously. Ample evidence exists:
      entropic considerations provide restrictions on the form of suitable ansatz
      states, and numerical studies show that certain tensor networks can indeed
      approximate the associated correlation functions. Here, we provide a complete
      positive answer to this question in the case of MPSs and 2D conformal field
      theory: we give quantitative estimates for the approximation error when
      approximating correlation functions by MPSs. Our work is constructive and yields
      an explicit MPS, thus providing both suitable initial values and a rigorous
      justification of variational methods.

PMID- 27689265
TI  - Dense Axion Stars.
AB  - If the dark matter particles are axions, gravity can cause them to coalesce into
      axion stars, which are stable gravitationally bound systems of axions. In the
      previously known solutions for axion stars, gravity and the attractive force
      between pairs of axions are balanced by the kinetic pressure. The mass of these
      dilute axion stars cannot exceed a critical mass, which is about 10^{-14}M_{?} if
      the axion mass is 10^{-4}  eV. We study axion stars using a simple approximation
      to the effective potential of the nonrelativistic effective field theory for
      axions. We find a new branch of dense axion stars in which gravity is balanced by
      the mean-field pressure of the axion Bose-Einstein condensate. The mass on this
      branch ranges from about 10^{-20}M_{?} to about M_{?}. If a dilute axion star
      with the critical mass accretes additional axions and collapses, it could produce
      a bosenova, leaving a dense axion star as the remnant.

PMID- 27689266
TI  - Two-Flavor Simulations of rho(770) and the Role of the KK[over -] Channel.
AB  - The rho(770) meson is the most extensively studied resonance in lattice QCD
      simulations in two (N_{f}=2) and three (N_{f}=2+1) flavor formulations. We
      analyze N_{f}=2 lattice scattering data using unitarized chiral perturbation
      theory, allowing not only for the extrapolation in mass but also in flavor,
      N_{f}=2->N_{f}=2+1. The flavor extrapolation requires information from a global
      fit to pipi and piK phase shifts from experiment. While the chiral extrapolation
      of N_{f}=2 lattice data leads to masses of the rho(770) meson far below the
      experimental one, we find that the missing KK[over -] channel is able to explain
      this discrepancy.

PMID- 27689267
TI  - Formation of CN^{-}, C_{3}N^{-}, and C_{5}N^{-} Molecules by Radiative Electron
      Attachment and their Destruction by Photodetachment.
AB  - The existence of negative ions in interstellar clouds has been associated for
      several decades with the process of radiative electron attachment. In this
      Letter, we report compelling evidence supporting the fact that the radiative
      attachment of a low-energy electron is inefficient to form the carbon chain
      anions CN^{-}, C_{3}N^{-}, and C_{5}N^{-} detected in interstellar clouds. The
      validity of the approach is confirmed by good agreement with experimental data
      obtained for the inverse photodetachment process, which represents the major
      cause of anion destruction in interstellar space. As a consequence, we suggest
      alternative models that could explain the formation of anions.

PMID- 27689262
TI  - Dark Matter Results from First 98.7 Days of Data from the PandaX-II Experiment.
AB  - We report the weakly interacting massive particle (WIMP) dark matter search
      results using the first physics-run data of the PandaX-II 500 kg liquid xenon
      dual-phase time-projection chamber, operating at the China JinPing underground
      laboratory. No dark matter candidate is identified above background. In
      combination with the data set during the commissioning run, with a total exposure
      of 3.3*10^{4}  kg day, the most stringent limit to the spin-independent
      interaction between the ordinary and WIMP dark matter is set for a range of dark
      matter mass between 5 and 1000  GeV/c^{2}. The best upper limit on the scattering
      cross section is found 2.5*10^{-46}  cm^{2} for the WIMP mass 40  GeV/c^{2} at
      90% confidence level.

PMID- 27689268
TI  - Rydberg Molecule-Induced Remote Spin Flips.
AB  - We have performed high resolution photoassociation spectroscopy of rubidium
      ultralong-range Rydberg molecules in the vicinity of the 25P state. Because of
      the hyperfine interaction in the ground state perturber atom, the emerging mixed
      singlet-triplet potentials contain contributions from both hyperfine states. We
      show that this can be used to induce remote spin flips in the perturber atom upon
      excitation of a Rydberg molecule. Furthermore, when the spin-orbit splitting of
      the Rydberg state is comparable to the hyperfine splitting in the ground state,
      the orbital angular momentum of the Rydberg electron is entangled with the
      nuclear spin of the perturber atom. Our results open new possibilities for the
      implementation of spin-dependent interactions for ultracold atoms in bulk systems
      and in optical lattices.

PMID- 27689269
TI  - Coherence Preservation of a Single Neutral Atom Qubit Transferred between Magic
      Intensity Optical Traps.
AB  - We demonstrate that the coherence of a single mobile atomic qubit can be well
      preserved during a transfer process among different optical dipole traps (ODTs).
      This is a prerequisite step in realizing a large-scale neutral atom quantum
      information processing platform. A qubit encoded in the hyperfine manifold of an
      ^{87}Rb atom is dynamically extracted from the static quantum register by an
      auxiliary moving ODT and reinserted into the static ODT. Previous experiments
      were limited by decoherences induced by the differential light shifts of qubit
      states. Here, we apply a magic-intensity trapping technique which mitigates the
      detrimental effects of light shifts and substantially enhances the coherence time
      to 225+/-21  ms. The experimentally demonstrated magic trapping technique relies
      on the previously neglected hyperpolarizability contribution to the light shifts,
      which makes the light shift dependence on the trapping laser intensity parabolic.
      Because of the parabolic dependence, at a certain "magic" intensity, the first
      order sensitivity to trapping light-intensity variations over ODT volume is
      eliminated. We experimentally demonstrate the utility of this approach and
      measure hyperpolarizability for the first time. Our results pave the way for
      constructing scalable quantum-computing architectures with single atoms trapped
      in an array of magic ODTs.

PMID- 27689271
TI  - Quantum Phase Transition in the Finite Jaynes-Cummings Lattice Systems.
AB  - Phase transitions are commonly held to occur only in the thermodynamical limit of
      a large number of system components. Here, we exemplify at the hand of the
      exactly solvable Jaynes-Cummings (JC) model and its generalization to finite JC
      lattices that finite component systems of coupled spins and bosons may exhibit
      quantum phase transitions (QPTs). For the JC model we find a continuous symmetry
      breaking QPT, a photonic condensate with a macroscopic occupation as the ground
      state, and a Goldstone mode as a low-energy excitation. For the two site JC
      lattice we show analytically that it undergoes a Mott-insulator to superfluid
      QPT. We identify as the underlying principle of the emergence of finite system
      QPTs the combination of increasing atomic energy and increasing interaction
      strength between the atom and the bosonic mode, which allows for the exploration
      of an increasingly large portion of the infinite dimensional Hilbert space of the
      bosonic mode. This suggests that finite system phase transitions will be present
      in a broad range of physical systems.

PMID- 27689270
TI  - Observation of Parity-Time Symmetry in Optically Induced Atomic Lattices.
AB  - We experimentally demonstrate PT-symmetric optical lattices with periodical gain
      and loss profiles in a coherently prepared four-level N-type atomic system. By
      appropriately tuning the pertinent atomic parameters, the onset of PT-symmetry
      breaking is observed through measuring an abrupt phase-shift jump between
      adjacent gain and loss waveguides. The experimental realization of such a readily
      reconfigurable and effectively controllable PT-symmetric waveguide array
      structure sets a new stage for further exploiting and better understanding the
      peculiar physical properties of these non-Hermitian systems in atomic settings.

PMID- 27689272
TI  - Multimode Strong Coupling in Superconducting Cavity Piezoelectromechanics.
AB  - High-frequency mechanical resonators subjected to low thermal phonon occupancy
      are easier to be prepared to the ground state by direct cryogenic cooling. Their
      extreme stiffness, however, poses a significant challenge for external
      interrogations. Here we demonstrate a superconducting cavity
      piezoelectromechanical system in which multiple modes of a bulk acoustic
      resonator oscillating at 10 GHz are coupled to a planar microwave superconducting
      resonator with a cooperativity exceeding 2*10^{3}, deep in the strong coupling
      regime. By implementation of the noncontact coupling scheme to reduce mechanical
      dissipation, the system exhibits excellent coherence characterized by a frequency
      quality-factor product of 7.5*10^{15}  Hz. Interesting dynamics of classical
      temporal oscillations of the microwave energy is observed, implying the coherent
      conversion between phonons and photons. The demonstrated high-frequency cavity
      piezoelectromechanics is compatible with superconducting qubits, representing an
      important step towards hybrid quantum systems.

PMID- 27689273
TI  - Torsional Optomechanics of a Levitated Nonspherical Nanoparticle.
AB  - An optically levitated nanoparticle in vacuum is a paradigm optomechanical system
      for sensing and studying macroscopic quantum mechanics. While its center-of-mass
      motion has been investigated intensively, its torsional vibration has only been
      studied theoretically in limited cases. Here we report the first experimental
      observation of the torsional vibration of an optically levitated nonspherical
      nanoparticle in vacuum. We achieve this by utilizing the coupling between the
      spin angular momentum of photons and the torsional vibration of a nonspherical
      nanoparticle whose polarizability is a tensor. The torsional vibration frequency
      can be 1 order of magnitude higher than its center-of-mass motion frequency,
      which is promising for ground state cooling. We propose a simple yet novel scheme
      to achieve ground state cooling of its torsional vibration with a linearly
      polarized Gaussian cavity mode. A levitated nonspherical nanoparticle in vacuum
      will also be an ultrasensitive nanoscale torsion balance with a torque detection
      sensitivity on the order of 10^{-29}  N m/sqrt[Hz] under realistic conditions.

PMID- 27689274
TI  - Optomagnonic Whispering Gallery Microresonators.
AB  - Magnons in ferrimagnetic insulators such as yttrium iron garnet (YIG) have
      recently emerged as promising candidates for coherent information processing in
      microwave circuits. Here we demonstrate optical whispering gallery modes of a YIG
      sphere interrogated by a silicon nitride photonic waveguide, with quality factors
      approaching 10^{6} in the telecom c band after surface treatments. Moreover, in
      contrast to conventional Faraday setups, this implement allows an input photon
      polarized colinearly to the magnetization to be scattered to a sideband mode of
      orthogonal polarization. This Brillouin scattering process is enhanced through
      triply resonant magnon, pump, and signal photon modes within an "optomagnonic
      cavity." Our results show the potential use of magnons for mediating microwave-to
      optical carrier conversion.

PMID- 27689275
TI  - Generation of Photon-Plasmon Quantum States in Nonlinear Hyperbolic
      Metamaterials.
AB  - We develop a general theoretical framework of integrated paired photon-plasmon
      generation through spontaneous wave mixing in nonlinear plasmonic and
      metamaterial nanostructures, rigorously accounting for material dispersion and
      losses in the quantum regime through the electromagnetic Green function. We
      identify photon-plasmon correlations in layered metal-dielectric structures with
      70% internal heralding quantum efficiency and reveal a novel mechanism of
      broadband generation enhancement due to topological transition in hyperbolic
      metamaterials.

PMID- 27689276
TI  - On-Chip Strong Coupling and Efficient Frequency Conversion between Telecom and
      Visible Optical Modes.
AB  - While the frequency conversion of photons has been realized with various
      approaches, the realization of strong coupling between optical modes of different
      colors has never been reported. Here, we present an experimental demonstration of
      strong coupling between telecom (1550 nm) and visible (775 nm) optical modes on
      an aluminum nitride photonic chip. The nonreciprocal normal-mode splitting is
      demonstrated as a result of the coherent interference between photons with
      different colors. Furthermore, a wideband, bidirectional frequency conversion
      with 0.14 on-chip conversion efficiency and a bandwidth up to 1.2 GHz is
      demonstrated.

PMID- 27689277
TI  - Compton Scattered X-Gamma Rays with Orbital Momentum.
AB  - We study the possibility of producing x-gamma rays with orbital angular momentum
      by means of the inverse Compton backscattering between a high brightness electron
      beam and a twisted laser pulse. We use the classical electrodynamics retarded
      fields for evaluating the orbital angular momentum of the radiation and
      connecting it to that of the primary laser pulse. We then propose the
      dimensioning of a linearly polarized x-ray source with orbital angular momentum,
      starting from the parameters of operating Thomson setups.

PMID- 27689278
TI  - Nonlinear Plasmonic Sensing with Nanographene.
AB  - Plasmons provide excellent sensitivity to detect analyte molecules through their
      strong interaction with the dielectric environment. Plasmonic sensors based on
      noble metals are, however, limited by the spectral broadening of these
      excitations. Here we identify a new mechanism that reveals the presence of
      individual molecules through the radical changes that they produce in the
      plasmons of graphene nanoislands. An elementary charge or a weak permanent dipole
      carried by the molecule are shown to be sufficient to trigger observable
      modifications in the linear absorption spectra and the nonlinear response of the
      nanoislands. In particular, a strong second-harmonic signal, forbidden by
      symmetry in the unexposed graphene nanostructure, emerges due to a redistribution
      of conduction electrons produced by interaction with the molecule. These results
      pave the way toward ultrasensitive nonlinear detection of dipolar molecules and
      molecular radicals that is made possible by the extraordinary optoelectronic
      properties of graphene.

PMID- 27689279
TI  - Internal Stresses Lead to Net Forces and Torques on Extended Elastic Bodies.
AB  - A geometrically frustrated elastic body will develop residual stresses arising
      from the mismatch between the intrinsic geometry of the body and the geometry of
      the ambient space. We analyze these stresses for an ambient space with gradients
      in its intrinsic curvature, and show that residual stresses generate effective
      forces and torques on the center of mass of the body. We analytically calculate
      these forces in two dimensions, and experimentally demonstrate their action by
      the migration of a non-Euclidean gel disc in a curved Hele-Shaw cell. An
      extension of our analysis to higher dimensions shows that these forces are also
      generated in three dimensions, but are negligible compared to gravity.

PMID- 27689280
TI  - High-Brightness High-Energy Electron Beams from a Laser Wakefield Accelerator via
      Energy Chirp Control.
AB  - By designing a structured gas density profile between the dual-stage gas jets to
      manipulate electron seeding and energy chirp reversal for compressing the energy
      spread, we have experimentally produced high-brightness high-energy electron
      beams from a cascaded laser wakefield accelerator with peak energies in the range
      of 200-600 MeV, 0.4%-1.2% rms energy spread, 10-80 pC charge, and ~0.2  mrad rms
      divergence. The maximum six-dimensional brightness B_{6D,n} is estimated as
      ~6.5*10^{15}  A/m^{2}/0.1%, which is very close to the typical brightness of e
      beams from state-of-the-art linac drivers. These high-brightness high-energy e
      beams may lead to the realization of compact monoenergetic gamma-ray and intense
      coherent x-ray radiation sources.

PMID- 27689281
TI  - Waveform-Controlled Relativistic High-Order-Harmonic Generation.
AB  - We consider the efficiency limit of relativistic high-order-harmonic emission
      from solid targets achievable with tailored light fields. Using one-dimensional
      particle-in-cell simulations, the maximum energy conversion efficiency is shown
      to reach as high as 10% for the harmonics in the range of 80-200 eV and is
      largely independent of laser intensity and plasma density. The waveforms most
      effective at driving harmonics have a broad spectrum with a lower-frequency limit
      set by the width of the incident pulse envelope and an upper limit set by the
      relativistic plasma frequency.

PMID- 27689282
TI  - Zonal Flow Patterns: How Toroidal Coupling Induces Phase Jumps and Shear Layers.
AB  - A new, frequency modulation mechanism for zonal flow pattern formation is
      presented. The model predicts the probability distribution function of the flow
      strength as well as the evolution of the characteristic spatial scale. Magnetic
      toroidicity-induced global phase dynamics is shown to determine the spatial
      structure of the flow. A key result is the observation that global phase
      patterning can lead to zonal flow formation in the absence of turbulence
      inhomogeneity.

PMID- 27689283
TI  - Tricriticalities and Quantum Phases in Spin-Orbit-Coupled Spin-1 Bose Gases.
AB  - We study the zero-temperature phase diagram of a spin-orbit-coupled Bose-Einstein
      condensate of spin 1, with equally weighted Rashba and Dresselhaus couplings.
      Depending on the antiferromagnetic or ferromagnetic nature of the interactions,
      we find three kinds of striped phases with qualitatively different behaviors in
      the modulations of the density profiles. Phase transitions to the zero-momentum
      and the plane-wave phases can be induced in experiments by independently varying
      the Raman coupling strength and the quadratic Zeeman field. The properties of
      these transitions are investigated in detail, and the emergence of tricritical
      points, which are the direct consequence of the spin-dependent interactions, is
      explicitly discussed.

PMID- 27689284
TI  - Tuning the Fabrication of Nanostructures by Low-Energy Highly Charged Ions.
AB  - Slow highly charged ions have been utilized recently for the creation of monotype
      surface nanostructures (craters, calderas, or hillocks) in different materials.
      In the present study, we report on the ability of slow highly charged xenon ions
      (^{129}Xe^{Q+}) to form three different types of nanostructures on the LiF(100)
      surface. By increasing the charge state from Q=15 to Q=36, the shape of the
      impact induced nanostructures changes from craters to hillocks crossing an
      intermediate stage of caldera structures. A dimensional analysis of the
      nanostructures reveals an increase of the height up to 1.5 nm as a function of
      the potential energy of the incident ions. Based on the evolution of both the
      geometry and size of the created nanostructures, defect-mediated desorption and
      the development of a thermal spike are utilized as creation mechanisms of the
      nanostructures at low and high charge states, respectively.

PMID- 27689285
TI  - Giant Rashba Splitting in CH_{3}NH_{3}PbBr_{3} Organic-Inorganic Perovskite.
AB  - As they combine decent mobilities with extremely long carrier lifetimes, organic
      inorganic perovskites open a whole new field in optoelectronics. Measurements of
      their underlying electronic structure, however, are still lacking. Using angle
      resolved photoelectron spectroscopy, we measure the valence band dispersion of
      single-crystal CH_{3}NH_{3}PbBr_{3}. The dispersion of the highest energy band is
      extracted applying a modified leading edge method, which accounts for the
      particular density of states of organic-inorganic perovskites. The surface
      Brillouin zone is consistent with bulk-terminated surfaces both in the low
      temperature orthorhombic and the high-temperature cubic phase. In the low
      temperature phase, we find a ring-shaped valence band maximum with a radius of
      0.043  A^{-1}, centered around a 0.16 eV deep local minimum in the dispersion of
      the valence band at the high-symmetry point. Intense circular dichroism is
      observed. This dispersion is the result of strong spin-orbit coupling. Spin-orbit
      coupling is also present in the room-temperature phase. The coupling strength is
      one of the largest ones reported so far.

PMID- 27689286
TI  - Carrier-Multiplication-Induced Structural Change during Ultrafast Carrier
      Relaxation and Nonthermal Phase Transition in Semiconductors.
AB  - While being extensively studied as an important physical process to alter exciton
      population in nanostructures at the fs time scale, carrier multiplication has not
      been considered seriously as a major mechanism for phase transition. Real-time
      time-dependent density functional theory study of Ge_{2}Sb_{2}Te_{5} reveals that
      carrier multiplication can induce an ultrafast phase transition in the solid
      state despite that the lattice remains cold. The results also unify the
      experimental findings in other semiconductors for which the explanation remains
      to be the 30-year old phenomenological plasma annealing model.

PMID- 27689287
TI  - J_{eff} Description of the Honeycomb Mott Insulator alpha-RuCl_{3}.
AB  - Novel ground states might be realized in honeycomb lattices with strong spin
      orbit coupling. Here we study the electronic structure of alpha-RuCl_{3}, in
      which the Ru ions are in a d^{5} configuration and form a honeycomb lattice, by
      angle-resolved photoemission, x-ray photoemission, and electron energy loss
      spectroscopy supported by density functional theory and multiplet calculations.
      We find that alpha-RuCl_{3} is a Mott insulator with significant spin-orbit
      coupling, whose low energy electronic structure is naturally mapped onto J_{eff}
      states. This makes alpha-RuCl_{3} a promising candidate for the realization of
      Kitaev physics. Relevant electronic parameters such as the Hubbard energy U, the
      crystal field splitting 10 Dq, and the charge transfer energy Delta are
      evaluated.

PMID- 27689288
TI  - Anomalous Dynamical Behavior of Freestanding Graphene Membranes.
AB  - We report subnanometer, high-bandwidth measurements of the out-of-plane
      (vertical) motion of atoms in freestanding graphene using scanning tunneling
      microscopy. By tracking the vertical position over a long time period, a 1000
      fold increase in the ability to measure space-time dynamics of atomically thin
      membranes is achieved over the current state-of-the-art imaging technologies. We
      observe that the vertical motion of a graphene membrane exhibits rare long-scale
      excursions characterized by both anomalous mean-squared displacements and Cauchy
      Lorentz power law jump distributions.

PMID- 27689289
TI  - Observation of the Quantum Anomalous Hall Insulator to Anderson Insulator Quantum
      Phase Transition and its Scaling Behavior.
AB  - Fundamental insight into the nature of the quantum phase transition from a
      superconductor to an insulator in two dimensions, or from one plateau to the next
      or to an insulator in the quantum Hall effect, has been revealed through the
      study of its scaling behavior. Here, we report on the experimental observation of
      a quantum phase transition from a quantum-anomalous-Hall insulator to an Anderson
      insulator in a magnetic topological insulator by tuning the chemical potential.
      Our experiment demonstrates the existence of scaling behavior from which we
      extract the critical exponent for this quantum phase transition. We expect that
      our work will motivate much further investigation of many properties of quantum
      phase transition in this new context.

PMID- 27689290
TI  - Dynamical Buildup of a Quantized Hall Response from Nontopological States.
AB  - We consider a two-dimensional system initialized in a topologically trivial state
      before its Hamiltonian is ramped through a phase transition into a Chern
      insulator regime. This scenario is motivated by current experiments with
      ultracold atomic gases aimed at realizing time-dependent dynamics in topological
      insulators. Our main findings are twofold. First, considering coherent dynamics,
      the nonequilibrium Hall response is found to approach a topologically quantized
      time-averaged value in the limit of slow but nonadiabatic parameter ramps, even
      though the Chern number of the state remains trivial. Second, adding dephasing,
      the destruction of quantum coherence is found to stabilize this Hall response,
      while the Chern number generically becomes undefined. We provide a geometric
      picture of this phenomenology in terms of the time-dependent Berry curvature.

PMID- 27689291
TI  - Transition from Strong to Weak Electronic Coupling in a Single-Molecule Junction.
AB  - We have investigated charge transport in single-molecule junctions using gold
      nanoelectrodes at room and cryogenic (10 K) temperatures. A statistical analysis
      of the low-bias conductance, measured during the stretching of the molecular
      junctions, shows that the most probable single-molecule conductance is
      insensitive to the temperature as expected for off-resonant coherent transport.
      Low-temperature current-voltage measurements show that these junction
      conformations have a smooth tunnelinglike shape. While separating the electrodes
      further we find that, in about one-fourth of the cases, the junction switches in
      an abrupt way to a configuration with I-V characteristics exhibiting a gap around
      zero bias and resonances at finite bias. The analysis of the I-V shape and of the
      conductance distance dependence suggests a stretching-induced transition from the
      strong to the weak electronic coupling regime. The transition involves a large
      renormalization of the injection barrier and of the electronic coupling between
      the molecule and the electrodes.

PMID- 27689293
TI  - Relaxation of a Classical Spin Coupled to a Strongly Correlated Electron System.
AB  - A classical spin which is antiferromagnetically coupled to a system of strongly
      correlated conduction electrons is shown to exhibit unconventional real-time
      dynamics which cannot be described by Gilbert damping. Depending on the strength
      of the local Coulomb interaction U, the two main electronic dissipation channels,
      namely transport of excitations via correlated hopping and via excitations of
      correlation-induced magnetic moments, become active on largely different time
      scales. We demonstrate that correlations can lead to a strongly suppressed
      relaxation which so far has been observed in purely electronic systems only and
      which is governed here by proximity to the divergent magnetic time scale in the
      infinite-U limit.

PMID- 27689292
TI  - Origin of the Resistivity Anisotropy in the Nematic Phase of FeSe.
AB  - The in-plane resistivity anisotropy is studied in strain-detwinned single
      crystals of FeSe. In contrast to other iron-based superconductors, FeSe does not
      develop long-range magnetic order below the tetragonal-to-orthorhombic transition
      at T_{s}~90  K. This allows for the disentanglement of the contributions to the
      resistivity anisotropy due to nematic and magnetic orders. Comparing direct
      transport and elastoresistivity measurements, we extract the intrinsic
      resistivity anisotropy of strain-free samples. The anisotropy peaks slightly
      below T_{s} and decreases to nearly zero on cooling down to the superconducting
      transition. This behavior is consistent with a scenario in which the in-plane
      resistivity anisotropy is dominated by inelastic scattering by anisotropic spin
      fluctuations.

PMID- 27689294
TI  - Large Unidirectional Magnetoresistance in a Magnetic Topological Insulator.
AB  - We report current-direction dependent or unidirectional magnetoresistance (UMR)
      in magnetic or nonmagnetic topological insulator (TI) heterostructures,
      Cr_{x}(Bi_{1-y}Sb_{y})_{2-x}Te_{3}/(Bi_{1-y}Sb_{y})_{2}Te_{3}, that is several
      orders of magnitude larger than in other reported systems. From the magnetic
      field and temperature dependence, the UMR is identified to originate from the
      asymmetric scattering of electrons by magnons. In particular, the large magnitude
      of UMR is an outcome of spin-momentum locking and a small Fermi wave number at
      the surface of TI. In fact, the UMR is maximized around the Dirac point with the
      minimal Fermi wave number.

PMID- 27689295
TI  - Resonant Inelastic X-Ray Scattering Response of the Kitaev Honeycomb Model.
AB  - We calculate the resonant inelastic x-ray scattering (RIXS) response of the
      Kitaev honeycomb model, an exactly solvable quantum-spin-liquid model with
      fractionalized Majorana and flux excitations. We find that the fundamental RIXS
      channels, the spin-conserving (SC) and the non-spin-conserving (NSC) ones, do not
      interfere and give completely different responses. SC RIXS picks up exclusively
      the Majorana sector with a pronounced momentum dispersion, whereas NSC RIXS also
      creates immobile fluxes, thereby rendering the response only weakly momentum
      dependent, as in the spin structure factor measured by inelastic neutron
      scattering. RIXS can, therefore, pick up the fractionalized excitations of the
      Kitaev spin liquid separately, making it a sensitive probe to detect spin-liquid
      character in potential material incarnations of the Kitaev honeycomb model.

PMID- 27689296
TI  - Compensated Semimetal LaSb with Unsaturated Magnetoresistance.
AB  - By combining angle-resolved photoemission spectroscopy and quantum oscillation
      measurements, we performed a comprehensive investigation on the electronic
      structure of LaSb, which exhibits near-quadratic extremely large
      magnetoresistance (XMR) without any sign of saturation at magnetic fields as high
      as 40 T. We clearly resolve one spherical and one intersecting-ellipsoidal hole
      Fermi surfaces (FSs) at the Brillouin zone (BZ) center Gamma and one ellipsoidal
      electron FS at the BZ boundary X. The hole and electron carriers calculated from
      the enclosed FS volumes are perfectly compensated, and the carrier compensation
      is unaffected by temperature. We further reveal that LaSb is topologically
      trivial but shares many similarities with the Weyl semimetal TaAs family in the
      bulk electronic structure. Based on these results, we have examined the
      mechanisms that have been proposed so far to explain the near-quadratic XMR in
      semimetals.

PMID- 27689297
TI  - Observation of the Transition from Lasing Driven by a Bosonic to a Fermionic
      Reservoir in a GaAs Quantum Well Microcavity.
AB  - We show that, by monitoring the free carrier reservoir in a GaAs-based quantum
      well microcavity under nonresonant pulsed optical pumping, lasing supported by a
      fermionic reservoir (photon lasing) can be distinguished from lasing supported by
      a reservoir of bosons (polariton lasing). Carrier densities are probed by
      measuring the photocurrent between lateral contacts deposited directly on the
      quantum wells of a microcavity that are partially exposed by wet chemical
      etching. We identify two clear thresholds in the input-output characteristic of
      the photoluminescence signal which can be attributed to polariton and photon
      lasing, respectively. The power dependence of the probed photocurrent shows a
      distinct kink at the threshold power for photon lasing due to an increased
      radiative recombination of free carriers as stimulated emission into the cavity
      mode sets in. At the polariton lasing threshold, on the other hand, the nonlinear
      increase of the luminescence is caused by stimulated scattering of exciton
      polaritons to the ground state which do not contribute directly to the
      photocurrent.

PMID- 27689298
TI  - Rotator-to-Lamellar Phase Transition in Janus Colloids Driven by Pressure
      Anisotropy.
AB  - We demonstrate through Brownian dynamics simulations a phase transition in
      plastic crystalline assemblies of Janus spheres through controlled pressure
      anisotropy. When the pressure in plane with hexagonally ordered layers is
      increased relative to that normal to the layers, a rapid first-order rotator-to
      lamellar transition of Janus sphere orientation occurs at constant temperature.
      We show that the underlying mechanism closely follows the Maier-Saupe theory,
      originally developed for isotropic-to-nematic transition in positionally
      disordered materials but here applied to positionally ordered ones. Since the
      transition involves almost no translational diffusion or volume change, and
      occurs rapidly by particle rotation, the results should help guide the design of
      rapidly switchable colloidal crystals.

PMID- 27689299
TI  - Embodiment of Learning in Electro-Optical Signal Processors.
AB  - Delay-coupled electro-optical systems have received much attention for their
      dynamical properties and their potential use in signal processing. In particular,
      it has recently been demonstrated, using the artificial intelligence algorithm
      known as reservoir computing, that photonic implementations of such systems solve
      complex tasks such as speech recognition. Here, we show how the backpropagation
      algorithm can be physically implemented on the same electro-optical delay-coupled
      architecture used for computation with only minor changes to the original design.
      We find that, compared to when the backpropagation algorithm is not used, the
      error rate of the resulting computing device, evaluated on three benchmark tasks,
      decreases considerably. This demonstrates that electro-optical analog computers
      can embody a large part of their own training process, allowing them to be
      applied to new, more difficult tasks.

PMID- 27689300
TI  - Erratum: Topological Optical Waveguiding in Silicon and the Transition between
      Topological and Trivial Defect States [Phys. Rev. Lett. 116, 163901 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.116.163901.

PMID- 27689301
TI  - Erratum: Compression-Driven Mass Flow in Bulk Solid ^{4}He [Phys. Rev. Lett. 117,
      025301 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.117.025301.

PMID- 27689302
TI  - Biocompatible and High Stiffness Nanophotonic Trap Array for Precise and
      Versatile Manipulation.
AB  - The advent of nanophotonic evanescent field trapping and transport platforms has
      permitted increasingly complex single molecule and single cell studies on-chip.
      Here, we present the next generation of nanophotonic Standing Wave Array Traps
      (nSWATs) representing a streamlined CMOS fabrication process and compact
      biocompatible design. These devices utilize silicon nitride (Si3N4) waveguides,
      operate with a biofriendly 1064 nm laser, allow for several watts of input power
      with minimal absorption and heating, and are protected by an anticorrosive layer
      for sustained on-chip microelectronics in aqueous salt buffers. In addition, due
      to Si3N4's negligible nonlinear effects, these devices can generate high
      stiffness traps while resolving subnanometer displacements for each trapped
      particle. In contrast to traditional table-top counterparts, the stiffness of
      each trap in an nSWAT device scales linearly with input power and is independent
      of the number of trapping centers. Through a unique integration of microcircuitry
      and photonics, the nSWAT can robustly trap, and controllably position, a large
      number of nanoparticles along the waveguide surface, operating in an all-optical,
      constant-force mode without need for active feedback. By reducing device
      fabrication cost, minimizing trapping laser specimen heating, increasing trapping
      force, and implementing commonly used trapping techniques, this new generation of
      nSWATs significantly advances the development of a high performance, low cost
      optical tweezers array laboratory on-chip.

PMID- 27689303
TI  - Difference of auditory brainstem responses by stimulating to round and oval
      window in animal experiments.
AB  - ABSTACT To ensure the safety and efficacy of implantable hearing aids, animal
      experiments are an essential developmental procedure, in particular, auditory
      brainstem responses (ABRs) can be used to verify the objective effectiveness of
      implantable hearing aids. This study measured and compared the ABRs generated
      when applying the same vibration stimuli to an oval window and round window. The
      ABRs were measured using a TDT system 3 (TDT, USA), while the vibration stimuli
      were applied to a round window and oval window in 4 guinea pigs using a piezo
      electric transducer with a proper contact tip. A paired t-test was used to
      determine any differences between the ABR amplitudes when applying the
      stimulation to an oval window and round window. The paired t-test revealed a
      significant difference between the ABR amplitudes generated by the round and oval
      window stimulation (t = 10.079, alpha < .0001). Therefore, the results confirmed
      that the biological response to round window stimulation was not the same as that
      to oval window stimulation.

PMID- 27689305
TI  - Energy evaluation of protection effectiveness of anti-vibration gloves.
AB  - This article describes an energy method of assessing protection effectiveness of
      anti-vibration gloves on the human dynamic structure. The study uses dynamic
      models of the human and the glove specified in Standard No. ISO 10068:2012. The
      physical models of human-tool systems were developed by combining human physical
      models with a power tool model. The combined human-tool models were then
      transformed into mathematical models from which energy models were finally
      derived. Comparative energy analysis was conducted in the domain of rms powers.
      The energy models of the human-tool systems were solved using numerical
      simulation implemented in the MATLAB/Simulink environment. The simulation
      procedure demonstrated the effectiveness of the anti-vibration glove as a method
      of protecting human operators of hand-held power tools against vibration. The
      desirable effect is achieved by lowering the flow of energy in the human-tool
      system when the anti-vibration glove is employed.

PMID- 27689304
TI  - Effects of post-harvest stigmasterol treatment on quality-related parameters and
      antioxidant enzymes of green asparagus (Asparagus officinalis L.).
AB  - The effects of immersion of green asparagus spears in stigmasterol solution (0,
      0.5 and 1.0 g l-1, 15 min, 25 degrees C) on weight loss, surface colour, enzyme
      activities and content of malondialdehyde, total phenol, lignin and chlorophyll
      were investigated during 40 days of storage at 4 +/- 0.5 degrees C. Of the
      concentrations tested, 0.5 g l-1 treatment was most effective. Stigmasterol (0.5
      g l-1) treatment significantly reduced colour changes and losses of fresh weight
      and chlorophyll content. Superoxide dismutase (SOD) and catalase (CAT) activities
      were maintained higher in stigmasterol-treated (0.5 g l-1) asparagus, whereas the
      activity of peroxidase (POD) was significantly reduced. Stigmasterol treatment
      (0.5 g l-1) also significantly decreased the content of malondialdehyde (MDA) and
      increased total phenol content. Accumulation of lignin was positively correlated
      to activity of guaiacol-POD (r = 0.960, p < 0.01) in stigmasterol-treated (0.5 g
      l-1) asparagus. The polyphenol oxidase (PPO) activity decreased and showed a
      significant negative correlation with the chroma L* value (r = -0.899, p < 0.01)
      in stigmasterol-treated (0.5 g l-1) asparagus. It was concluded that stigmasterol
      treatment (0.5 g l-1) could inhibit the senescence of green asparagus, and
      therefore prolong its shelf-life, maintaining the quality of post-harvest green
      asparagus.

PMID- 27689306
TI  - Tobacco 21: An Important Public Policy to Protect Our Youth.
AB  - An important approach to reduce youth tobacco use is the adoption of regulations
      to prohibit tobacco product sale to individuals younger than 21 years, termed
      Tobacco 21. In the United States, close to 90% of current smokers started smoking
      before the age of 18 years, and 99% before age 26 years. Earlier age of tobacco
      use initiation is associated with lower rates of smoking cessation. Increasing
      minimum age to purchase has been shown to reduce tobacco product use among youth.
      The critical determinant is likely the loss of social sources of tobacco
      products. Enforcement activities are important for age-of-purchase laws to be
      effective. Raising the minimum legal age to purchase tobacco products to 21 years
      is highly supported among both the smoking and nonsmoking public. Tobacco sales
      to those younger than 21 years account for just 2% of total tobacco sales, yet
      produce 90% of new smokers. The short-term effect on small business of raising
      the minimum age to purchase would be minimal. Small businesses will have time to
      adapt to the decrease in tobacco sales as fewer youth grow up nicotine addicted.
      Raising the minimum age to purchase of tobacco and nicotine products to 21 years,
      combined with enforcement of those restrictions, will help protect future
      generations from a lifetime of tobacco dependence and associated morbidity. These
      regulations should apply to all tobacco products, including electronic nicotine
      delivery systems. Respiratory health care providers should educate their local,
      state, and federal policy makers on the importance of Tobacco 21.

PMID- 27689307
TI  - Serum protein concentration in low-dose total body irradiation of normal and
      malnourished rats.
AB  - Among the radiotherapeutics' modalities, total body irradiation (TBI) is used as
      treatment for certain hematological, oncological and immunological diseases. The
      aim of this study was to evaluate the long-term effects of low-dose TBI on plasma
      concentration of total protein and albumin using prematurely and undernourished
      rats as animal model. For this, four groups with 9 animals each were formed:
      Normal nourished (N); Malnourished (M); Irradiated Normal nourished (IN);
      Irradiated Malnourished (IM). At the age of 28 days, rats of the IN and IM groups
      underwent total body gamma irradiation with a source of cobalt-60. Total protein
      and Albumin in the blood serum was quantified by colorimetry. This research
      indicates that procedures involving low-dose total body irradiation in children
      have repercussions in the reduction in body-mass as well as in the plasma levels
      of total protein and albumin. Our findings reinforce the periodic monitoring of
      total serum protein and albumin levels as an important tool in long-term follow
      up of pediatric patients in treatments associated to total body irradiation.

PMID- 27689308
TI  - Determination of the conventional true value of gamma-ray air kerma in a minitype
      reference radiation.
AB  - To develop mobile calibration equipment for gamma-ray dose or dose rate meters in
      the field of radiation protection, a minitype reference radiation (MRR) of
      0.5m*0.5m*0.5m cube was set up and used for investigation. Two types, which add
      up to 12 daily used gamma-ray dose rate meters, were used as samples to determine
      the conventional true value of air kerma (CAK) at the point of test in the MRR. A
      gamma-ray spectrometer was also used to monitor the scattering gamma rays in the
      MRR, which were applied further to characterize the disturbance of scattering
      gamma ray in CAK determination. On the basis of the sample data sets of CAKs,
      scattering gamma spectra and air kerma values at the point of test without sample
      meters, a CAK prediction model at the point of test was developed by the least
      square support vector machine, which is a multiple nonlinear regression method.
      For reducing the amount of data and improving the regression efficiency,
      principal component analysis (PCA) was used to extract feature components from
      the scattering gamma-ray spectra before regression. A relative standard
      uncertainty of 4.65% was achieved in determining CAK in the MRR using the
      constructed prediction model.

PMID- 27689309
TI  - A novel method of combined detector model for gamma-ray densitometer: Theoretical
      calculation and MCNP4C simulation.
AB  - This study focuses on investigating a new model of combined backscatter and
      transmission method for nuclear densitometer. In this method for density
      measurement, a true combination of transmission and backscatter methods was
      studied and related equations were developed. The MCNP4C code was used for
      simulation of this combined detector model (CDM) and by applying theoretical
      calculations, density equation was corrected for the proposed nuclear
      densitometer. In the new method presented here, the buildup effect was estimated
      by an online system that was improved in our laboratory and was replaced by a new
      conceptual calculation. Hence, for the purpose of buildup reduction, there was no
      need for the shield around the detector, as it was monitored and reduced online.
      Furthermore, this study showed that the RSQ function could be improved by the
      CDM. The measurement technique proposed in this study has a better linearity
      trend than the transmission technique. Thus, the ability of CDM to improve the
      accuracy of the nuclear densitometer was shown.

PMID- 27689310
TI  - VoxelMages: a general-purpose graphical interface for designing geometries and
      processing DICOM images for PENELOPE.
AB  - The design and construction of geometries for Monte Carlo calculations is an
      error-prone, time-consuming, and complex step in simulations describing particle
      interactions and transport in the field of medical physics. The software
      VoxelMages has been developed to help the user in this task. It allows to design
      complex geometries and to process DICOM image files for simulations with the
      general-purpose Monte Carlo code PENELOPE in an easy and straightforward way.
      VoxelMages also allows to import DICOM-RT structure contour information as
      delivered by a treatment planning system. Its main characteristics, usage and
      performance benchmarking are described in detail.

PMID- 27689311
TI  - Gaseous nitrous acid (HONO) and nitrogen oxides (NOx) emission from gasoline and
      diesel vehicles under real-world driving test cycles.
AB  - : Reactive nitrogen species emission from the exhausts of gasoline and diesel
      vehicles, including nitrogen oxides (NOx) and nitrous acid (HONO), contributes as
      a significant source of photochemical oxidant precursors in the ambient air.
      Multiple laboratory and on-road exhaust measurements have been performed to
      estimate the NOx emission factors from various vehicles and their contribution to
      atmospheric pollution. Meanwhile, HONO emission from vehicle exhaust has been
      under-measured despite the fact that HONO can contribute up to 60% of the total
      hydroxyl budget during daytime and its formation pathway is not fully understood.
      A profound traffic-induced HONO to NOx ratio of 0.8%, established by Kurtenbach
      et al. since 2001, has been widely applied in various simulation studies and
      possibly linked to under-estimation of HONO mixing ratios and OH radical budget
      in the morning. The HONO/NOx ratios from direct traffic emission have become
      debatable when it lacks measurements for direct HONO emission from vehicles upon
      the fast-changing emission reduction technology. Several recent studies have
      reported updated values for this ratio. This study has reported the measurement
      of HONO and NOx emission as well as the estimation of exhaust-induced HONO/NOx
      ratios from gasoline and diesel vehicles using different chassis dynamometer
      tests under various real-world driving cycles. For the tested gasoline vehicle,
      which was equipped with three-way catalyst after-treatment device, HONO/NOx
      ratios ranged from 0 to 0.95 % with very low average HONO concentrations. For the
      tested diesel vehicle equipped with diesel particulate active reduction device,
      HONO/NOx ratios varied from 0.16 to 1.00 %. The HONO/NOx ratios in diesel exhaust
      were inversely proportional to the average speeds of the tested vehicles.
      IMPLICATIONS: Photolysis of HONO is a dominant source of morning OH radicals.
      Conventional traffic-induced HONO/NOx ratio of 0.8% has possibly linked to
      underestimation of the total HONO budget and consequently underestimation of OH
      radical budget. The recently reported HONO/NOx ratio of ~1.6% was used to
      stimulate HONO emission, which resulted in increased HONO concentrations during
      morning peak hours and its impact of 14% OH increment in the morning. However,
      the results were still lower than the measured concentrations. More studies
      should be conducted to establish an updated traffic-induced HONO/NOx ratio.

PMID- 27689312
TI  - The effects of informal carers' characteristics on their information needs: The
      information needs state approach.
AB  - BACKGROUND: There has been little research that provides a comprehensive account
      of the nature and aspects of information needs of informal carers. The authors
      have previously developed and validated a framework that accounts for major
      underlying states of information need. This paper aims to apply this framework to
      explore whether there are common demographic and socioeconomic characteristics
      that affect the information needs states of carers. A questionnaire about the
      information needs states was completed by 198 carers above 18 years old. We use
      statistical methods to look for similarities and differences in respondents'
      information needs states, in terms of the demographic and socioeconomic
      variables. At least one information needs state varies among carers, in terms of
      seven demographic and socioeconomic variables: the age of the patient(s) that
      they are caring for; the condition(s) of the patient(s) that they are caring for;
      the number of patients that they are caring for; their length of time as a carer;
      their gender; the country that they live in; and the population of the area that
      they live in. The findings demonstrate the utility of the information needs state
      framework. We outline some practical implications of the framework.

PMID- 27689313
TI  - A review of fundamental principles for animal models of DOHaD research: an
      Australian perspective.
AB  - Epidemiology formed the basis of 'the Barker hypothesis', the concept of
      'developmental programming' and today's discipline of the Developmental Origins
      of Health and Disease (DOHaD). Animal experimentation provided proof of the
      underlying concepts, and continues to generate knowledge of underlying
      mechanisms. Interventions in humans, based on DOHaD principles, will be informed
      by experiments in animals. As knowledge in this discipline has accumulated, from
      studies of humans and other animals, the complexity of interactions between
      genome, environment and epigenetics, has been revealed. The vast nature of
      programming stimuli and breadth of effects is becoming known. As a result of our
      accumulating knowledge we now appreciate the impact of many variables that
      contribute to programmed outcomes. To guide further animal research in this
      field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of
      DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in
      Melbourne, Australia in April 2015. This review summarizes the contributions of
      animal research to the understanding of DOHaD, and makes recommendations for the
      design and conduct of animal experiments to maximize relevance, reproducibility
      and translation of knowledge into improving health and well-being.

PMID- 27689314
TI  - Reversible Polymorphism, Liquid Crystallinity, and Stimuli-Responsive
      Luminescence in a Bola-amphiphilic pi-System: Structure-Property Correlations
      Through Nanoindentation and DFT Calculations.
AB  - We report the design, synthesis, detailed characterization, and analysis of a new
      multifunctional pi-conjugated bola-amphiphilic chromophore: oligo-(p
      phenyleneethynylene)dicarboxylic acid with dialkoxyoctadecyl side chains (OPE-C18
      1). OPE-C18-1 shows two polymorphs at 123 K (OPE-C18-1') and 373 K (OPE-C18-1"),
      whose crystal structures were characterized via single crystal X-ray diffraction.
      OPE-C18-1 also exhibits thermotropic liquid crystalline property revealing a
      columnar phase. The inherent pi-conjugation of OPE-C18-1 imparts luminescence to
      the system. Photoluminescence measurements on the mesophase also reveal similar
      luminescence as in the crystalline state. Additionally, OPE-C18-1 shows mechano
      hypsochromic luminescence behavior. Density functional theory (DFT)-based
      calculations unravel the origins behind the simultaneous existence of all these
      properties. Nanoindentation experiments on the single crystal reveal its
      mechanical strength and accurately correlate the molecular arrangement with the
      liquid crystalline and mechanochromic luminescence behavior.

PMID- 27689315
TI  - Pilot testing of the "First You Should Get Stronger" program among caregivers of
      older adults with dementia.
AB  - OBJECTIVE: In this study, randomized controlled interventional study pattern was
      used to examine the effects of the "First You Should Get Stronger" program on the
      caregiving burden and healthy life style behavior of caregivers of dementia
      patients. METHODS: "Zarit Caregiver Burden Scale" and "Healthy Life Style
      Behavior Scale" were used. The study was completed with 40 caregivers in total
      with 20 in the intervention group and 20 in the control group. A statistically
      significant difference was determined between the "Zarit Caregiving Burden Scale"
      and "Healthy Life Style Behavior Scale" score averages of the intervention group
      that participated in the "First You Should Get Stronger" program in comparison
      with those of the control group. RESULTS: It is important for the healths of
      caregivers to include similar programs for the caregivers of dementia patients in
      continuous and regular applications. DISCUSSION: The results highlight the
      importance of the "First You Should Get Stronger" program significantly decreased
      the caregiving burden and significantly developed the healthy lifestyle behaviors
      of caregivers in the intervention group. Since dementia is a difficult
      neurological syndrome with patients cared at home, it generally wears out the
      caregivers significantly. It is suggested that the nurses and healthcare
      professionals working with dementia patients are evaluated separately and that
      they carry out caregiving applications within the scope of the "First You Should
      Get Stronger" program.

PMID- 27689316
TI  - Results of scalp cooling during anthracycline containing chemotherapy depend on
      scalp skin temperature.
AB  - OBJECTIVES: The success of scalp cooling in preventing or reducing chemotherapy
      induced alopecia (CIA) is highly variable between patients undergoing similar
      chemotherapy regimens. A decrease of the scalp skin temperature seems to be an
      important factor, but data on the optimum temperature reached by scalp cooling to
      prevent CIA are lacking. This study investigated the relation between scalp skin
      temperature and its efficacy to prevent CIA. MATERIALS AND METHODS: In this
      explorative study, scalp skin temperature was measured during scalp cooling in 62
      breast cancer patients undergoing up to six cycles of anthracycline containing
      chemotherapy. Scalp skin temperature was measured by using two thermocouples at
      both temporal sides of the head. The primary end-point was the need for a wig or
      other head covering. RESULTS: Maximal cooling was reached after 45 min and was
      continued for 90 min after chemotherapy infusion. The scalp skin temperature
      after 45 min cooling varied from 10  degrees C to 31  degrees C, resulting in a
      mean scalp skin temperature of 19  degrees C (SEM: 0,4). Intrapersonal scalp skin
      temperatures during cooling were consistent for each chemotherapy cycle (ANOVA: P
      = 0,855). Thirteen out of 62 patients (21%) did not require a wig or other head
      covering. They appeared to have a significantly lower mean scalp skin temperature
      (18  degrees C; SEM: 0,7) compared to patients with alopecia (20  degrees C; SEM:
      0,5) (P = 0,01). CONCLUSION: The efficacy of scalp cooling during chemotherapy is
      temperature dependent. A precise cut-off point could not be detected, but the
      best results seem to be obtained when the scalp temperature decreases below 18 
      degrees C. TRIALREGISTER. NL NTR NUMBER: 3082.

PMID- 27689318
TI  - Phthalates in Fast Food: A Potential Dietary Source of Exposure.

PMID- 27689317
TI  - The effect of in-hospital acquired thrombocytopenia on the outcome of patients
      with acute coronary syndromes: A systematic review and meta-analysis.
AB  - BACKGROUND: In-hospital acquired thrombocytopenia (TP) is relatively common among
      patients hospitalized with acute coronary syndromes (ACS). However, its effect on
      short-term and long-term outcomes has yet to be reviewed systematically. METHODS:
      We conducted a systematic review and meta-analysis of clinical studies assessing
      the relationship between new-onset in-hospital TP and adverse outcomes among ACS
      patients. MEDLINE, Scopus and the Cochrane Library were searched for eligible
      studies published before March 20, 2016. RESULTS: Ten studies reporting on a
      total of 142,161 ACS patients were identified. 8133 patients showed evidence of
      new-onset TP during the course of their hospitalization. Compared with patients
      with normal platelet counts, patients with new-onset TP had a prolonged in
      hospital stay, significantly higher risk of both short-term mortality (<30days)
      (Odds ratio (OR) [95% confidence interval (CI)]: 5.58 [3.63-8.57]) and late death
      (6months to 1year) (OR [95% CI]: 3.45 [2.35-5.07]), as well as a significantly
      higher risk of major bleeding events in the first 30days (OR [95% CI]: 6.93 [5.13
      9.38]). In addition, risk for other secondary cardiovascular endpoints, including
      recurrent myocardial infarction, stroke, in-hospital heart failure, stent
      thrombosis and unplanned revascularization was also significantly higher in the
      TP versus the no TP group. CONCLUSIONS: Development of TP during the in-hospital
      management of ACS patients is a significant predictor of both short- and long
      term adverse events, including mortality. In the light of this evidence,
      clinicians should be cautious and closely monitor abnormal platelet counts that
      present early following an ACS.

PMID- 27689319
TI  - Field-based Evaluation of a Novel SPME-GC-MS Method for Investigation of Below
      ground Interaction between Brassica Roots and Larvae of Cabbage Root Fly, Delia
      radicum L.
AB  - INTRODUCTION: Collection of volatiles from plant roots poses technical challenges
      due to difficulties accessing the soil environment without damaging the roots.
      OBJECTIVES: To validate a new non-invasive method for passive sampling of root
      volatiles in situ, from plants grown under field conditions, using solid phase
      micro-extraction (SPME). METHODS: SPME fibres were inserted into perforated
      polytetrafluoroethene (PTFE) tubes positioned in the soil next to broccoli plants
      for collection of root volatiles pre- and post-infestation with Delia radicum
      larvae. After sample analysis by gas chromatography-mass spectrometry (GC-MS),
      principal component analysis (PCA) was applied to determine differences in the
      profiles of volatiles between samples. RESULTS: GC-MS analysis revealed that this
      method can detect temporal changes in root volatiles emitted before and after
      Delia radicum damage. PCA showed that samples collected pre- and post-infestation
      were compositionally different due to the presence of root volatiles induced by
      D. radicum feeding. Sulphur containing compounds, in particular, accounted for
      the differences observed. Root volatiles emission patterns post-infestation are
      thought to follow the feeding and developmental progress of larvae. CONCLUSION:
      This study shows that volatiles released by broccoli roots can be collected in
      situ using SPME fibres within perforated PTFE tubes under field conditions.
      Plants damaged by Delia radicum larvae could be distinguished from plants sampled
      pre-infestation and soil controls on the basis of larval feeding-induced sulphur
      containing volatiles. These results show that this new method is a powerful tool
      for non-invasive sampling of root volatiles below-ground. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27689321
TI  - Fatigued Elderly Adults with End-Stage Renal Disease are More Likely to have Low
      Bone Mass than those Who are not Fatigued.

PMID- 27689320
TI  - Local depletion of glycogen with supramaximal exercise in human skeletal muscle
      fibres.
AB  - KEY POINTS: Glycogen is stored in local spatially distinct compartments within
      skeletal muscle fibres and is the main energy source during supramaximal
      exercise. Using quantitative electron microscopy, we show that supramaximal
      exercise induces a differential depletion of glycogen from these compartments and
      also demonstrate how this varies with fibre types. Repeated exercise alters this
      compartmentalized glycogen depletion. The results obtained in the present study
      help us understand the muscle metabolic dynamics of whole body repeated
      supramaximal exercise, and suggest that the muscle has a compartmentalized local
      adaptation to repeated exercise, which affects glycogen depletion. ABSTRACT:
      Skeletal muscle glycogen is heterogeneously distributed in three separated
      compartments (intramyofibrillar, intermyofibrillar and subsarcolemmal). Although
      only constituting 3-13% of the total glycogen volume, the availability of
      intramyofibrillar glycogen is of particular importance to muscle function. The
      present study aimed to investigate the depletion of these three subcellular
      glycogen compartments during repeated supramaximal exercise in elite athletes.
      Ten elite cross-country skiers (aged 25 +/- 4 years, VO2 max : 65 +/- 4 ml kg-1 
      min-1 ; mean +/- SD) performed four ~4 min supramaximal sprint time trials (STT 1
      4) with 45 min of recovery. The subcellular glycogen volumes in musculus triceps
      brachii were quantified from electron microscopy images before and after both STT
      1 and 4. During STT 1, the depletion of intramyofibrillar glycogen was higher in
      type 1 fibres [-52%; (-89:-15%)] than type 2 fibres [-15% (-52:22%)] (P = 0.02),
      whereas the depletion of intermyofibrillar glycogen [main effect: -19% (-33:0%),
      P = 0.006] and subsarcolemmal glycogen [main effect: -35% (-66:0%), P = 0.03] was
      similar between fibre types. By contrast, only intermyofibrillar glycogen volume
      was significantly reduced during STT 4, in both fibre types [main effect: -31% (
      50:-11%), P = 0.002]. Furthermore, for each of the subcellular compartments, the
      depletion of glycogen during STT 1 was associated with the volumes of glycogen
      before STT 1. In conclusion, the depletion of spatially distinct glycogen
      compartments differs during supramaximal exercise. Furthermore, the depletion
      changes with repeated exercise and is fibre type-dependent.

PMID- 27689322
TI  - Case-specific potentiation of glioblastoma drugs by pterostilbene.
AB  - Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant
      primary brain tumor in adults. Addressing the shortage of effective treatment
      options for this cancer, we explored repurposing of existing drugs into
      combinations with potent activity against GBM cells. We report that the
      phytoalexin pterostilbene is a potentiator of two drugs with previously reported
      anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant
      sertraline. Combinations of either of these two compounds with pterostilbene
      suppress cell growth, viability, sphere formation and inhibit migration in tumor
      GBM cell (GC) cultures. The potentiating effect of pterostilbene was observed to
      a varying degree across a panel of 41 patient-derived GCs, and correlated in a
      case specific manner with the presence of missense mutation of EGFR and PIK3CA
      and a focal deletion of the chromosomal region 1p32. We identify pterostilbene
      induced cell cycle arrest, synergistic inhibition of MAPK activity and induction
      of Thioredoxin interacting protein (TXNIP) as possible mechanisms behind
      pterostilbene's effect. Our results highlight a nontoxic stilbenoid compound as a
      modulator of anticancer drug response, and indicate that pterostilbene might be
      used to modulate two anticancer compounds in well-defined sets of GBM patients.

PMID- 27689323
TI  - ADH1B and CDH1 polymorphisms predict prognosis in male patients with non
      metastatic laryngeal cancer.
AB  - In this study, we assessed the association between single nucleotide
      polymorphisms (SNPs) in candidate genes and the prognosis of laryngeal cancer
      (LC) patients. Thirty-seven SNPs in 26 genes were genotyped in 170 male Han
      Chinese patients with LC. The effects of the candidate genes on the prognosis of
      LC patients were evaluated using Kaplan-Meier curves and Cox proportional hazards
      regression models. The GA genotype of rs1229984 (hazard ratio [HR], 0.537; 95%
      confidence interval [CI], 0.340-0.848; p = 0.008) in alcohol dehydrogenase 1B
      (ADH1B), and the AA genotype of rs9929218 (HR, 6.074; 95% CI, 1.426-25.870; p =
      0.015) in CDH1 were associated with overall survival. Our data suggest that
      polymorphisms in ADH1B and CDH1 may be prognostic indicators in LC.

PMID- 27689324
TI  - Enhancement of endothelial permeability by free fatty acid through lysosomal
      cathepsin B-mediated Nlrp3 inflammasome activation.
AB  - Obesity is an important risk factor for exacerbating chronic diseases such as
      cardiovascular disease and cancer. High serum level of saturated free fatty acids
      such as palmitate is an important contributor for obesity-induced diseases. Here,
      we examined the contribution of inflammasome activation in vascular cells to free
      fatty acid-induced endothelial dysfunction and vascular injury in obesity. Our
      findings demonstrated that high fat diet-induced impairment of vascular integrity
      and enhanced vascular permeability in the myocardium in mice were significantly
      attenuated by Nlrp3 gene deletion. In microvascular endothelial cells (MVECs),
      palmitate markedly induces Nlrp3 inflammasome complex formation leading to
      caspase-1 activation and IL1beta production. By fluorescence microscopy and flow
      cytometry, we observed that such palmitate-induced Nlrp3 inflammasome activated
      was accompanied by a reduction in inter-endothelial tight junction proteins ZO
      1/ZO-2. Such palmitate-induced decrease of ZO-1/ZO-2 was also correlated with an
      increase in the permeability of endothelial monolayers treated with palmitates.
      Moreover, palmitate-induced alterations in ZO-1/ZO-2 or permeability were
      significantly reversed by an inflammasome activity inhibitor, YVAD, or a high
      mobility group box 1 (HMGB1) activity inhibitor glycyrrhizin. Lastly, blockade of
      cathepsin B with Ca-074Me significantly abolished palmitate-induced activation of
      Nlrp3 inflammasomes, down-regulation of ZO-1/ZO-2, and enhanced permeability in
      MVECs or their monolayers. Together, these data strongly suggest that activation
      of endothelial inflammasomes due to increased free fatty acids produces HMGB1,
      which disrupts inter-endothelial junctions and increases paracellular
      permeability of endothelium contributing to early onset of endothelial injury
      during obesity.

PMID- 27689325
TI  - Catalytically defective receptor protein tyrosine kinase PTK7 enhances invasive
      phenotype by inducing MMP-9 through activation of AP-1 and NF-kappaB in
      esophageal squamous cell carcinoma cells.
AB  - Protein tyrosine kinase 7 (PTK7), a member of the catalytically defective
      receptor protein tyrosine kinase family, is upregulated in various cancers
      including esophageal squamous cell carcinoma (ESCC). Here, we have explored the
      molecular mechanism of PTK7-dependent invasiveness in ESCC cells. PTK7 knockdown
      reduced gelatin degradation and MMP-9 secretion in cultures of ESCC TE-10 cells,
      and showed reduced levels of MMP9 mRNA using real-time RT-PCR and luciferase
      reporter assays. PTK7 knockdown decreased not only phosphorylation of NF-kappaB,
      IkappaB, ERK, and JNK, but also nuclear localization of NF-kappaB and AP-1
      consisting of c-Fos and c-Jun. Activation of AP-1 and NF-kappaB requires PTK7
      mediated activation of tyrosine kinases, including Src. In addition, NF-kappaB
      activation by PTK7 involves the PI3K/Akt signaling pathway. PTK7-mediated
      upregulation of MMP9 was also observed in other ESCC cell lines and in three
      dimensional cultures of TE-10 cells. Moreover, MMP-9 expression positively
      correlated with PTK7 expression in ESCC tumor tissue. These findings demonstrate
      that PTK7 upregulates MMP9 through activation of AP-1 and NF-kappaB and, thus
      increases invasive properties of ESCC cells.

PMID- 27689326
TI  - An artificial lncRNA targeting multiple miRNAs overcomes sorafenib resistance in
      hepatocellular carcinoma cells.
AB  - Sorafenib resistance remains a major obstacle for the effective treatment of
      hepatocellular carcinoma (HCC), and a number of miRNAs contribute to this
      resistance. However, the regulatory networks of miRNAs are very complex, thus
      inhibiting a single miRNA may sequentially activate other compensatory pathways.
      In the present study, we generated an artificial long non-coding RNA (AlncRNA),
      which simultaneously targets multiple miRNAs including miR-21, miR-153, miR-216a,
      miR-217, miR-494 and miR-10a-5p. These miRNAs have been shown to be upregulated
      in sorafenib-resistant cells and participate in the mechanisms underlying
      sorafenib resistance. The AlncRNA contains tandem sequences of 6 copies of the
      complementary binding sequences to the target miRNAs and is expressed by an
      adenoviral vector (Ad5-AlncRNA). Infection of Ad5-AlncRNA into sorafenib
      resistant HCC cells blocked the function of miRNAs, and sequentially inhibited
      the downregulation of PTEN and activation of AKT. Ad5-AlncRNA significantly
      inhibited proliferation and induced apoptosis of sorafenib-resistant cells and
      enhanced the effects of sorafenib in vitro and in animal models. Inhibition of
      autophagy decreased the sensitivity of sorafenib-resistant cells to Ad5-AlncRNA,
      while its induction had the opposite effect. These results indicate that
      targeting multiple miRNAs by the artificial lncRNA could be a potential promising
      strategy for overcoming sorafenib resistance in the treatment of HCC.

PMID- 27689327
TI  - Low carbohydrate diet prevents Mcl-1-mediated resistance to BH3-mimetics.
AB  - Overexpression of Mcl-1 is implicated in resistance of several cancers to
      chemotherapeutic treatment, therefore identifying a safe way to decrease its
      expression in tumor cells represents a central goal. We investigated if a
      modulation of the diet could impact on Mcl-1 expression using a Myc-driven
      lymphoma model. We established that a partial reduction of caloric intake by 25%
      represents an efficient way to decrease Mcl-1 expression in tumor cells.
      Furthermore, using isocaloric custom diets, we observed that carbohydrates (CHO)
      are the main regulators of Mcl-1 expression within the food. Indeed, feeding
      lymphoma-bearing mice with a diet having 25% less carbohydrates was sufficient to
      decrease Mcl-1 expression by 50% in lymphoma cells. We showed that a low CHO diet
      resulted in AMPK activation and mTOR inhibition leading to eukaryotic elongation
      factor 2 (eEF2) inhibition, blocking protein translation elongation. Strikingly,
      a low CHO diet was sufficient to sensitize Myc-driven lymphoma-bearing mice to
      ABT-737-induced cell death in vivo. Thus reducing carbohydrate intake may
      represent a safe way to decrease Mcl-1 expression and to sensitize tumor cells to
      anti-cancer therapeutics.

PMID- 27689328
TI  - c-MYC drives histone demethylase PHF8 during neuroendocrine differentiation and
      in castration-resistant prostate cancer.
AB  - Epigenetic factors play critical roles in prostate cancer (PCa) development.
      However, how they contribute to neuroendocrine differentiation (NED) and
      castration-resistant PCa (CRPC) is not fully understood. Using bioinformatics and
      biochemical approaches to analyze cell-based models of NED and CRPC, we found a
      cluster of epigenetic factors whose expression is downregulated during NED and
      upregulated in CRPC (i.e. follow a Down-Up pattern). Two histone demethylases
      within this cluster, PHF8 and KDM3A, are post-transcriptionally regulated by c
      MYC through miR-22, which targets both PHF8 and KDM3A. We also found that the c
      MYC/miR-22/PHF8 axis is downstream of androgen receptor (AR) signaling in CRPC
      cells. The co-expression of PHF8 with AR in clinical CRPC samples, normal mouse
      prostate, and adenocarcinomas of the prostate during PCa progression in a
      transgenic (TRAMP) mouse model supports the connection between PHF8 and AR.
      Knockdown of PHF8 impedes cell cycle progression in CRPC cells and has more
      profound effects on their growth than on the parental LNCaP cell line.
      Furthermore, PHF8 knockdown sensitizes LNCaP-Abl cells to the AR antagonist
      enzalutamide. Our data reveal novel mechanisms that underlie the regulation of
      PHF8 and KDM3A during NED and in CRPC, and support the candidacy of PHF8 as a
      therapeutic target in CRPC.

PMID- 27689329
TI  - Age and cellular context influence rectal prolapse formation in mice with caecal
      wall colorectal cancer xenografts.
AB  - In patients with rectal prolapse is the prevalence of colorectal cancer
      increased, suggesting that a colorectal tumor may induce rectal prolapse.
      Establishment of tumor xenografts in immunodeficient mice after orthotopic
      inoculations of human colorectal cancer cells into the caecal wall is a widely
      used approach for the study of human colorectal cancer progression and
      preclinical evaluation of therapeutics. Remarkably, 70% of young mice carrying a
      COLO320DM caecal tumor showed symptoms of intussusception of the large bowel
      associated with intestinal lumen obstruction and rectal prolapse. The quantity of
      the COLO320DM bioluminescent signal of the first three weeks post-inoculation
      predicts prolapse in young mice. Rectal prolapse was not observed in adult mice
      carrying a COLO320DM caecal tumor or young mice carrying a HT29 caecal tumor. In
      contrast to HT29 tumors, which showed local invasion and metastasis, COLO320DM
      tumors demonstrated a non-invasive tumor with pushing borders without presence of
      metastasis. In conclusion, rectal prolapse can be linked to a non-invasive, space
      occupying COLO320DM tumor in the gastrointestinal tract of young immunodeficient
      mice. These data reveal a model that can clarify the association of patients
      showing rectal prolapse with colorectal cancer.

PMID- 27689330
TI  - Interconnections between apoptotic and autophagic pathways during thiopurine
      induced toxicity in cancer cells: the role of reactive oxygen species.
AB  - Thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) are a class of
      genotoxic drugs extensively used in the treatment of various illnesses including
      leukemia. Their underlying molecular mechanism of action involves the activation
      of apoptosis and autophagy but remains widely unclear. Here we present evidence
      that autophagy induction by thiopurines is a survival mechanism that antagonizes
      apoptosis and is involved in degrading damaged mitochondria through mitophagy. On
      the other hand, apoptosis is the main cell death mechanism by thiopurines as its
      inhibition prohibited cell death. Thus a tight interplay between apoptosis and
      autophagy controls cell fate in response to thiopurine treatment. Moreover,
      thiopurines disrupt mitochondrial function and induce a loss of the mitochondrial
      transmembrane potential. The involvement of the mitochondrial pathway in
      thiopurine-induced apoptosis was further confirmed by increased formation of
      reactive oxygen species (ROS). Inhibiting oxidative stress protected the cells
      from thiopurine-induced cell death and ROS scavenging prohibited autophagy
      induction by thiopurines. Our data indicate that the anticarcinogenic effects of
      thiopurines are mediated by complex interplay between cellular mechanisms
      governing redox homeostasis, apoptosis and autophagy.

PMID- 27689331
TI  - Fluorescence-guided surgery of a highly-metastatic variant of human triple
      negative breast cancer targeted with a cancer-specific GFP adenovirus prevents
      recurrence.
AB  - We have previously developed a genetically-engineered GFP-expressing telomerase
      dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In
      the present report, we demonstrate that targeting a triple-negative high-invasive
      human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables
      curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection
      and prevented local recurrence and greatly inhibited lymph-node metastasis due to
      the ability of the virus to selectively label and subsequently kill cancer cells.
      In contrast, residual breast cancer cells become more aggressive after bright
      (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival
      compared with conventional BLS. Thus, metastasis from a highly-aggressive triple
      negative breast cancer can be prevented by FGS in a clinically-relevant mouse
      model.

PMID- 27689332
TI  - Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent
      copy number variation in IPO11 and prognostic significance of importin-11
      overexpression on poor survival.
AB  - Non-muscle-invasive bladder cancer (NMIBC) often has a worse prognosis following
      its progression to muscle-invasive bladder cancer (MIBC), despite radical
      cystectomy with pelvic lymph node dissection combined with chemotherapy.
      Therefore, the discovery of novel biomarkers for predicting the progression of
      this disease and of therapeutic targets for preventing it is crucial. We
      performed whole-exome sequencing to analyze superficial tumor tissues (Tsup) and
      basal tumor tissues (Tbas) from 3 MIBC patients and identified previously
      unreported copy number variations in IPO11 that warrants further investigation as
      a molecular target. In addition, we identified a significant association between
      the absolute copy number and mRNA expression of IPO11 and found that high
      importin-11 expression was correlated with poor 3-year overall survival (OS),
      cancer-specific survival (CSS) and cancer-free survival (CFS) compared with low
      expression in the BCa patients. Importin-11 overexpression was also an
      independent risk factor for CSS and CFS in the BCa patients. Our study has
      revealed that IPO11 copy number amplification contributes to its overexpression
      and that these changes are unfavorable prognostic factors in NMIBC. Thus, IPO11
      copy number amplification and importin-11 overexpression are promising biomarkers
      for predicting the progression and poor prognosis of patients with NMIBC.

PMID- 27689333
TI  - Curcumin targets the TFEB-lysosome pathway for induction of autophagy.
AB  - Curcumin is a hydrophobic polyphenol derived from the herb Curcumalonga and its
      wide spectrum of pharmacological activities has been widely studied. It has been
      reported that Curcumin can induce autophagy through inhibition of the Akt-mTOR
      pathway. However, the effect of Curcumin on lysosome remains largely elusive. In
      this study, we first found that Curcumin treatment enhances autophagic flux in
      both human colon cancer HCT116 cells and mouse embryonic fibroblasts (MEFs).
      Moreover, Curcumin treatment promotes lysosomal function, evidenced by the
      increased lysosomal acidification and enzyme activity. Second, Curcumin is
      capable of suppressing the mammalian target of rapamycin (mTOR). Interestingly,
      Curcumin fails to inhibit mTOR and to activate lysosomal function in Tsc2-/-MEFs
      with constitutive activation of mTOR, indicating that Curcumin-mediated lysosomal
      activation is achieved via suppression of mTOR. Third, Curcumin treatment
      activates transcription factor EB (TFEB), a key nuclear transcription factor in
      control of autophagy and lysosome biogenesis and function, based on the following
      observations: (i) Curcumin directly binds to TFEB, (ii) Curcumin promotes TFEB
      nuclear translocation; and (iii) Curcumin increases transcriptional activity of
      TFEB. Finally, inhibition of autophagy and lysosome leads to more cell death in
      Curcumin-treated HCT116 cells, suggesting that autophagy and lysosomal activation
      serves as a cell survival mechanism to protect against Curcumin-mediated cell
      death. Taken together, data from our study provide a novel insight into the
      regulatory mechanisms of Curcumin on autophagy and lysosome, which may facilitate
      the development of Curcumin as a potential cancer therapeutic agent.

PMID- 27689334
TI  - Clinicopathological characteristics and long-term prognosis of screening detected
      non-palpable breast cancer by ultrasound in hospital-based Chinese population
      (2001-2014).
AB  - PURPOSE: The mainstay modality of breast cancer screening in China is the
      hospital-based opportunistic screening among asymptomatic self-referred women.
      There is little data about the ultrasound (US) detected non-palpable breast
      cancer (NPBC) in Chinese population. METHODS: We analyzed 699 consecutive NPBC
      from 1.8-2.3 million asymptomatic women from 2001 to 2014, including 572 US
      detected NPBC from 3,786 US-positive women and 127 mammography (MG) detected NPBC
      from 788 MG-positive women. The clinicopathological features, disease-free
      survival (DFS) and overall survival (OS) were compared between the US- and MG
      detected NPBC. Prognostic factors of NPBC were identified. RESULTS: Compared to
      MG, US could detect more invasive NPBC (83.6% vs 54.3%, p<0.001), lymph node
      positive NPBC (19.1% vs 10.2%, p=0.018), lower grade (24.8% vs 16.5%, p<0.001),
      multifocal (19.2% vs 6.3%, p<0.001), PR positive (71.4% vs 66.9%, p=0.041), Her2
      negative (74.3% vs 54.3%, p<0.001), Ki67 high (defined as >14%, 46.3% vs 37.0%,
      p=0.031) cancers and more NPBC who received chemotherapy (40.7% vs 21.3%,
      p<0.001). There was no significant difference in 10-year DFS and OS between US
      detected vs MG-detected NPBC, DCIS and invasive NPBC. For all NPBC and the US
      detected NPBC, the common DFS-predictors included pT, pN, p53 and bilateral
      cancers. CONCLUSION: US could detect more invasive, node-positive, multifocal
      NPBC in hospital-based asymptomatic Chinese female, who could achieve comparable
      10-year DFS and OS as MG-detected NPBC. US would not delay early detection of
      NPBC with improved cost-effectiveness, thus could serve as the feasible initial
      imaging modality in hospital-based opportunistic screening among Chinese women.

PMID- 27689336
TI  - Keratin 18-deficiency results in steatohepatitis and liver tumors in old mice: A
      model of steatohepatitis-associated liver carcinogenesis.
AB  - : Backround: Steatohepatitis (SH)-associated liver carcinogenesis is an
      increasingly important issue in clinical medicine. SH is morphologically
      characterized by steatosis, hepatocyte injury, ballooning, hepatocytic
      cytoplasmic inclusions termed Mallory-Denk bodies (MDBs), inflammation and
      fibrosis. RESULTS: 17-20-months-old Krt18-/- and Krt18+/- mice in contrast to wt
      mice spontaneously developed liver lesions closely resembling the morphological
      spectrum of human SH as well as liver tumors. The pathologic alterations were
      more pronounced in Krt18-/- than in Krt18+/- mice. The frequency of liver tumors
      with male predominance was significantly higher in Krt18-/- compared to age
      matched Krt18+/- and wt mice. Krt18-deficient tumors in contrast to wt animals
      displayed SH features and often pleomorphic morphology. aCGH analysis of tumors
      revealed chromosomal aberrations in Krt18-/- liver tumors, affecting loci of
      oncogenes and tumor suppressor genes. MATERIALS AND METHODS: Livers of 3-, 6-, 12
      and 17-20-months-old aged wild type (wt), Krt18+/- and Krt18-/- (129P2/OlaHsd
      background) mice were analyzed by light and immunofluorescence microscopy as well
      as immunohistochemistry. Liver tumors arising in aged mice were analyzed by array
      comparative genomic hybridization (aCGH). CONCLUSIONS: Our findings show that K18
      deficiency of hepatocytes leads to steatosis, increasing with age, and finally to
      SH. K18 deficiency and age promote liver tumor development in mice, frequently on
      the basis of chromosomal instability, resembling human HCC with stemness
      features.

PMID- 27689337
TI  - p53 in the mitochondria, as a trans-acting protein, provides error-correction
      activities during the incorporation of non-canonical dUTP into DNA.
AB  - Mutations in mitochondrial DNA is an outcome of errors produced by DNA polymerase
      gamma during replication and failure of the repair mechanism. Misincorporation of
      non-canonical dUTP leads to mutagenesis or apoptosis, and may contribute to the
      cytotoxic effects of 5'-fluorouracil chemotherapy. Tumor suppressor p53 protein
      in the mitochondria displays physical and functional interactions with
      mitochondrial DNA and polymerase gamma, and by its intrinsic 3'->5' exonuclease
      activity can diminish the polymerization errors. Here we demonstrate the impact
      of p53 on incorporation of uracil into DNA examined with mitochondrial fractions,
      as the source of polymerase gamma. p53 in mitochondria facilitates DNA damage
      repair functions resulting from uracil-DNA misincorporation. Our biochemical
      studies revealed that the procession of U:A and mismatched U:G lesions enhances
      in the presence of recombinant or endogenous cytoplasmic p53. p53 in mitochondria
      can function as an exonuclease/proofreader for polymerase gamma by either
      decreasing the incorporation of non-canonical dUTP into DNA or by promoting the
      excision of incorporated nucleotide from nascent DNA, thus expanding the spectrum
      of DNA damage sites exploited for proofreading as a trans-acting protein. The
      data suggest that p53 may contribute to defense of the cells from consequences of
      dUTP misincorporation in both normal and tumor cells.

PMID- 27689335
TI  - Co-application of canavanine and irradiation uncouples anticancer potential of
      arginine deprivation from citrulline availability.
AB  - The moderate anticancer effect of arginine deprivation in clinical trials has
      been linked to an induced argininosuccinate synthetase (ASS1) expression in
      initially ASS1-negative tumors, and ASS1-positive cancers are anticipated as non
      responders. Our previous studies indicated that arginine deprivation and low
      doses of the natural arginine analog canavanine can enhance radioresponse.
      However, the efficacy of the proposed combination in the presence of
      extracellular citrulline, the substrate for arginine synthesis by ASS1, remains
      to be elucidated, in particular for malignant cells with positive and/or
      inducible ASS1 as in colorectal cancer (CRC). Here, the physiological citrulline
      concentration of 0.05 mM was insufficient to overcome cell cycle arrest and
      radiosensitization triggered by arginine deficiency. Hyperphysiological
      citrulline (0.4 mM) did not entirely compensate for the absence of arginine and
      significantly decelerated cell cycling. Similar levels of canavanine-induced
      apoptosis were detected in the absence of arginine regardless of citrulline
      supplementation both in 2-D and advanced 3-D assays, while normal colon
      epithelial cells in organoid/colonosphere culture were unaffected. Notably,
      canavanine tremendously enhanced radiosensitivity of arginine-starved 3-D CRC
      spheroids even in the presence of hyperphysiological citrulline. We conclude that
      the novel combinatorial targeting strategy of metabolic-chemo-radiotherapy has
      great potential for the treatment of malignancies with inducible ASS1 expression.

PMID- 27689338
TI  - Promoter methylation patterns of ABCB1, ABCC1 and ABCG2 in human cancer cell
      lines, multidrug-resistant cell models and tumor, tumor-adjacent and tumor
      distant tissues from breast cancer patients.
AB  - Overexpression of ABCB1, ABCC1 and ABCG2 in tumor tissues is considered a major
      cause of limited efficacy of anticancer drugs. Gene expression of ABC
      transporters is regulated by multiple mechanisms, including changes in the DNA
      methylation status. Most of the studies published so far only report promoter
      methylation levels for either ABCB1 or ABCG2, and data on the methylation status
      for ABCC1 are scarce. Thus, we determined the promoter methylation patterns of
      ABCB1, ABCC1 and ABCG2 in 19 human cancer cell lines. In order to contribute to
      the elucidation of the role of DNA methylation changes in acquisition of a
      multidrug resistant (MDR) phenotype, we also analyzed the promoter methylation
      patterns in drug-resistant sublines of the cancer cell lines GLC-4, SW1573, KB-3
      1 and HL-60. In addition, we investigated if aberrant promoter methylation levels
      of ABCB1, ABCC1 and ABCG2 occur in tumor and tumor-surrounding tissues from
      breast cancer patients.Our data indicates that hypomethylation of the ABCC1
      promoter is not cancer type-specific but occurs in cancer cell lines of different
      origins. Promoter methylation was found to be an important mechanism in gene
      regulation of ABCB1 in parental cancer cell lines and their drug-resistant
      sublines. Overexpression of ABCC1 in MDR cell models turned out to be mediated by
      gene amplification, not by changes in the promoter methylation status of ABCC1.
      In contrast to the promoters of ABCC1 and ABCG2, the promoter of ABCB1 was
      significantly higher methylated in tumor tissues than in tumor-adjacent and tumor
      distant tissues from breast cancer patients.

PMID- 27689340
TI  - Preferential 5-Methylcytosine Oxidation in the Linker Region of Reconstituted
      Positioned Nucleosomes by Tet1 Protein.
AB  - Tet (ten-eleven translocation) family proteins oxidize 5-methylcytosine (mC) to 5
      hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxycytosine (caC),
      and are suggested to be involved in the active DNA demethylation pathway. In this
      study, we reconstituted positioned mononucleosomes using CpG-methylated 382 bp
      DNA containing the Widom 601 sequence and recombinant histone octamer, and
      subjected the nucleosome to treatment with Tet1 protein. The sites of oxidized
      methylcytosine were identified by bisulfite sequencing. We found that, for the
      oxidation reaction, Tet1 protein prefers mCs located in the linker region of the
      nucleosome compared with those located in the core region.

PMID- 27689341
TI  - Extracellular mycosynthesis of silver nanoparticles and their microbicidal
      activity.
AB  - Myconanotechnology, a combination of mycology and nanotechnology that deals with
      the synthesis of nanoparticles using fungi or their metabolites, has great
      potential in the area of agriculture owing to the high surface-to-volume ratio
      and excellent biomedical, electronic, mechanical and physicochemical properties
      of these myconanoparticles. Extracellular mycosynthesis of Aspergillus flavus
      (KF934407) silver nanoparticles (AgNPs) was performed, which were produced by
      redox reaction. Furthermore, the extracellular synthesised AgNPs were
      characterised by ultraviolet/visible spectrophotometry, differential light
      scattering (DLS) and transmission electron microscopy. The bactericidal and
      fungicidal actions of synthesised silver myconanoparticles (myco-AgNPs) were
      studied against pathogenic bacteria and fungi. The formulated myco-AgNPs were
      spherical in shape, with a size in the range of 50nm and DLS at an intensity of
      107.8nm. The myco-AgNPs showed effective antimicrobial properties against
      Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Trichoderma spp.
      at high concentrations. In conclusion, AgNPs have a prolonged microbicidal effect
      as a result of continuous release of Ag+ at sufficient concentrations. Thus, A.
      flavus-based myco-AgNPs have the potential to be used as a non-toxic and cheap
      antimicrobial agent against various pathogenic bacteria and fungi.

PMID- 27689342
TI  - Syntheses and Structures of Xenon Trioxide Alkylnitrile Adducts.
AB  - The potent oxidizer and highly shock-sensitive binary noble-gas oxide XeO3
      interacts with CH3 CN and CH3 CH2 CN to form O3 XeNCCH3 , O3 Xe(NCCH3 )2 , O3
      XeNCCH2 CH3 , and O3 Xe(NCCH2 CH3 )2 . Their low-temperature single-crystal X-ray
      structures show that the xenon atoms are consistently coordinated to three donor
      atoms, which results in pseudo-octahedral environments around the xenon atoms.
      The adduct series provides the first examples of a neutral xenon oxide bound to
      nitrogen bases. Raman frequency shifts and Xe-N bond lengths are consistent with
      complex formation. Energy-minimized gas-phase geometries and vibrational
      frequencies were obtained for the model compounds O3 Xe(NCCH3 )n (n=1-3) and O3
      Xe(NCCH3 )n ?[O3 Xe(NCCH3 )2 ]2 (n=1, 2). Natural bond orbital (NBO), quantum
      theory of atoms in molecules (QTAIM), electron localization function (ELF), and
      molecular electrostatic potential surface (MEPS) analyses were carried out to
      further probe the nature of the bonding in these adducts.

PMID- 27689339
TI  - Circulating immune cells in multiple sclerosis.
AB  - Circulating T and B lymphocytes contribute to the pathogenesis of the
      neuroinflammatory autoimmune disease, multiple sclerosis (MS). Further progress
      in the development of MS treatments is dependent upon a greater understanding of
      the immunological disturbances that underlie the disease. Analyses of circulating
      immune cells by flow cytometry have revealed MS-associated alterations in the
      composition and function of T and B cell subsets, including temporal changes
      associated with disease activity. Disturbances in circulating immune populations
      reflect those observed in the central nervous system and include skewing towards
      proinflammatory CD4+ and CD8+ T cells and B cells, greater proportions of
      follicular T helper cells and functional defects in the corresponding T and B
      regulatory subsets. Utilizing the analytical power of modern flow cytometers,
      researchers are now well positioned to monitor immunological changes associated
      with disease activity or intervention, describe immunological signatures with
      predictive value and identify targets for therapeutic drug development. This
      review discusses the contribution of various T and B lymphocyte subsets to MS
      pathogenesis, provides current and relevant phenotypical descriptions to assist
      in experimental design and highlights areas of future research.

PMID- 27689343
TI  - A serum metabolomics-driven approach predicts orange juice consumption and its
      impact on oxidative stress and inflammation in subjects from the BIONAOS study.
AB  - SCOPE: To identify biomarkers of orange juice (OJ) consumption containing
      different doses of polyphenols and to determine its impact on oxidative stress
      and inflammation using an untargeted metabolomics analysis. METHODS AND RESULTS:
      Thirty subjects aged 22-63 years from the BIONAOS study consumed a normal
      polyphenol OJ (NPJ) or a high-polyphenol OJ (HPJ) (299 or 745 mg/L, respectively)
      for 12 weeks in a randomized, parallel, double-blind study. UHPLC-MS, univariate
      and multivariate statistical analysis and ROC curves were used to design
      biomarkers of consumption in serum. We propose betonicine, stachydrine, methyl
      glucopyranoside (alpha+beta), dihydroferulic acid and galactonate as a new
      metabolic signature to distinguish the intake of OJ with a different polyphenol
      content. Changes in metabolites related to OJ, oxidative stress and inflammation
      were observed. After HPJ consumption, the serum levels of hydroxyoctadecadienoic
      acid (9-HODE+13-HODE) and dihydroxyoctadecanoic acid (12,13-DiHOME and 9,10
      DiHOME) decreased, whereas levels of 12-hydroxyeicosatetraenoic acid (12-HETE)
      increased. 5-HETE increased after the NPJ intervention exclusively. CONCLUSION:
      We designed a new panel of biomarkers to differentiate the intake of OJs
      containing different doses of polyphenols. On the other hand, the consumption of
      an OJ with a high content of flavanones improved oxidative stress and
      inflammatory biomarkers.

PMID- 27689344
TI  - Evaluation of acute traumatic coagulopathy in dogs and cats following blunt force
      trauma.
AB  - OBJECTIVE: To evaluate the presence of acute traumatic coagulopathy (ATC) in dogs
      and cats following blunt trauma and to relate coagulation variables with injury
      severity and admission variables. DESIGN: Prospective, single center,
      observational study from 2013 to 2014. SETTING: Urban private referral hospital.
      ANIMALS: Eighteen and 19 client-owned dogs and cats, respectively, sustaining
      blunt trauma within 8 hours of presentation without prior resuscitation; 17
      healthy staff and client-owned control cats METHODS: Blood samples were collected
      upon presentation for measurement of blood gas, lactate, blood glucose, ionized
      calcium, PCV, total plasma protein, prothrombin time (PT), activated partial
      thromboplastin time (aPTT), fibrinogen, platelet count, and thromboelastography.
      RESULTS: ATC was diagnosed in 1 dog and 1 cat on presentation. Hypercoagulability
      was documented in 4/18 (22%) of dogs and 1/19 (5.3%) of cats. In dogs,
      prolongation of PT (P = 0.018), aPTT (P = 0.013) and decrease in maximum
      amplitude (MA) (P = 0.027) were significantly associated with injury severity as
      measured by the animal trauma triage (ATT) score. In cats, PT, aPTT, MA, and clot
      strength (G) were not associated with injury severity. In cats, increasing blood
      glucose and lactate were significantly associated with decreasing MA (P = 0.041,
      P = 0.031) and G (P = 0.014, P = 0.03). In both dogs (P = 0.002) and cats (P =
      0.007), fibrinogen concentration was significantly correlated with G.
      CONCLUSIONS: ATC is rare in minimally injured dogs and cats following blunt
      trauma. In dogs, ATT score is significantly associated with PT, aPTT, and MA,
      suggesting an increased risk of ATC in more severely injured animals. ATT score
      does not appear to predict coagulopathies in cats. Future studies including more
      severely injured animals are warranted to better characterize coagulation changes
      associated with blunt trauma.

PMID- 27689345
TI  - Ghrelin is a possible new predictor associated with executive function in
      patients with type 2 diabetes mellitus.
AB  - AIMS/INTRODUCTION: The aim of the present research was to study the ghrelin
      level, executive function and their possible association in patients with type 2
      diabetes mellitus. MATERIALS AND METHODS: A total of 370 people were recruited
      between March 2015 and March 2016 in this study. Among them, 212 participants
      were patients with type 2 diabetes mellitus and 158 participants were included as
      the control group. Their blood sample was analyzed for the level of ghrelin and
      other clinical indexes. Cognitive function was measured by the Montreal Cognitive
      Assessment, and executive function was evaluated by the Wisconsin Card Sorting
      Test. RESULTS: In the type 2 diabetes mellitus group, age, years of education,
      duration of diabetes, fasting blood glucose, glycated hemoglobin, hypertension
      and waist-to-hip ratio were correlated with total Montreal Cognitive Assessment
      scores. No association was found between ghrelin level and total Montreal
      Cognitive Assessment score in patients with type 2 diabetes mellitus. However,
      ghrelin was found to be a significant predictor for executive function impairment
      measured by the Wisconsin Card Sorting Test in patients with type 2 diabetes
      mellitus. CONCLUSIONS: The level of serum ghrelin might be a biomarker of
      executive function and become a strong predictor of executive function impairment
      in patients with type 2 diabetes mellitus. Ghrelin might have a potential
      protective effect against cognitive function impairment in type 2 diabetes
      patients.

PMID- 27689346
TI  - Homogeneous Cobalt/Vanadium Complexes as Precursors for Functionalized Mixed
      Oxides in Visible-Light-Driven Water Oxidation.
AB  - The heterometallic complexes (NH4 )2 [Co(H2 O)6 ]2 [V10 O28 ]?4 H2 O (1) and (NH4
      )2 [Co(H2 O)5 (beta-HAla)]2 [V10 O28 ]?4 H2 O (2) have been synthesized and used
      for the preparation of mixed oxides as catalysts for water oxidation. Thermal
      decomposition of 1 and 2 at relatively low temperatures (<500  degrees C) leads
      to the formation of the solid mixed oxides CoV2 O6 /V2 O5 (3) and Co2 V2 O7 /V2
      O5 (4). The complexes (1, 2) and heterogeneous materials (3, 4) act as catalysts
      for photoinduced water oxidation. A modification of the thermal decomposition
      procedure allowed the deposition of mixed metal oxides (MMO) on a mesoporous TiO2
      film. The electrodes containing Co/V MMOs in TiO2 films were used for
      electrocatalytic water oxidation and showed good stability and sustained anodic
      currents of about 5 mA cm-2 at 1.72 V versus relative hydrogen electrode (RHE).
      This method of functionalizing TiO2 films with MMOs at relatively low
      temperatures (<500  degrees C) can be used to produce other oxides with different
      functionality for applications in, for example, artificial photosynthesis.

PMID- 27689347
TI  - Variable Stiffness Fiber with Self-Healing Capability.
AB  - A variable stiffness fiber made of silicone and low melting point alloys quickly
      becomes >700 times softer and >400 times more deformable when heated above 62 
      degrees C. It shows remarkable self-healing properties and can be clamped,
      knitted, and bonded, as shown in a foldable multi-purpose drone, a wearable cast
      for bone injuries, and a soft multi-directional actuator.

PMID- 27689348
TI  - Neither nefopam nor acetaminophen can be used as postoperative analgesics in a
      rat model of ischemic stroke.
AB  - : Analgesics such as opioid agonists are usually not given during the
      postoperative phase of experimental stroke because they are susceptible to
      interfere with the evaluation of neuroprotective therapies. Here, we investigate
      the potential of acetaminophen and nefopam, two nonopioid analgesic drugs, to
      exert an analgesic effect without inducing neuroprotection in a murine model of
      ischemic stroke. We demonstrate that acetaminophen (200 mg/kg, PO) induces a
      significant decrease in the infarct volume, particularly in the cortex (VEHICLE:
      200.1 mm3 vs. ACETAMINOPHEN: 140.9 mm3 , P < 0.05), while nefopam (2, 20 or 40
      mg/kg, IM), administered at the end of middle cerebral artery occlusion (MCAO),
      do not influence the infarct size (VEHICLE: 268.6 mm3 vs. NEFOPAM 2: 248.8 mm3 ,
      NEFOPAM 20: 250.6 mm3 and NEFOPAM 40: 215.9 mm3 , P > 0.05). Moreover, we find
      that nefopam administration (20 mg/kg, IM) in the acute postoperative phase do
      not change the level of neuroprotection induced by MK801 (3 mg/kg, IV), a well
      known neuroprotectant (VEHICLE: 268.6 mm3 vs. MK801: 194.4 mm3 and vs. MK801 +
      NEFOPAM 20: 195.2 mm3 ). On the other hand, although nefopam induces analgesia in
      healthy animals, it is not the case when administered during MCAO (behavior
      scores at 5 min: HEALTHY: 2.1 vs. HEALTHY + NEFOPAM 20: 0.6, P < 0.5; IR: 0.40
      vs. IR + NEFOPAM 20: 0.67, P > 0.05). Our data suggest that neither acetaminophen
      nor nefopam can be used as analgesic agents to meet the needs of limiting rodent
      pain and distress during experimental stroke surgery.

PMID- 27689349
TI  - Striking impact of Na insertion on structural and electronic properties of the
      electrode material Na2+x V6O16.
AB  - The Na2.55V6O16 structure is a promising material for sodium ion batteries due to
      a significant capacity and stability at high current rates, but its cycle
      stability for Na application is significantly lower than that obtained with Li
      (de-)insertion. In this work, we present the results of density functional theory
      (DFT) calculations on the structural and electronic properties of Na2+x V6O16
      compounds up to x  =  2. As x increases, we evidence a strong deformation of the
      tetrahedral sites occupied by sodium ions, leading to new highly stable sites for
      these inserted ions at x  =  2. Comparing with Li4V6O16, we demonstrate that the
      stability of these new Na sites can be attributed to the electrostatic
      interactions between sodium ions and atoms of the host structure, the evolution
      of the oxidation degree of Vanadium atoms being another indicator of such
      effects.

PMID- 27689350
TI  - Kinetics of coffee industrial residue pyrolysis using distributed activation
      energy model and components separation of bio-oil by sequencing temperature
      raising pyrolysis.
AB  - This study was carried out to investigate the kinetics of coffee industrial
      residue (CIR) pyrolysis, the effect of pyrolysis factors on yield of bio-oil
      component and components separation of bio-oil. The kinetics of CIR pyrolysis was
      analyzed using distributed activation energy model (DAEM), based on the
      experiments in thermogravimetric analyzer (TGA), and it indicated that the
      average of activation energy (E) is 187.86kJ.mol-1. The bio-oils were prepared
      from CIR pyrolysis in vacuum tube furnace, and its components were determined by
      gas chromatography/mass spectrometry (GC-MS). Among pyrolysis factors, pyrolysis
      temperature is the most influential factor on components yield of bio-oil,
      directly concerned with the volatilization and yield of components (palmitic
      acid, linoleic acid, oleic acid, octadecanoic acid and caffeine). Furthermore, a
      new method (sequencing temperature-raising pyrolysis) was put forward and applied
      to the components separation of bio-oil. Based on experiments, a solution of
      components separation of bio-oil was come out.

PMID- 27689351
TI  - Enhanced lipid production in thermo-tolerant mutants of Chlorella pyrenoidosa
      NCIM 2738.
AB  - The present study aimed to develop thermo-tolerant mutants of Chlorella
      pyrenoidosa NCIM 2738 for high lipids production. For this, ethyl methane
      sulfonate was used, which generated two effective thermo-tolerant mutants, M18
      and M24 of Chlorella pyrenoidosa NCIM 2738, capable of surviving at temperature
      up to 47 degrees C and showing improved lipid and biomass yields. They showed
      59.62% and 50.75% increase, respectively in lipid content compared to wild type
      at 30 degrees C, which could not grow at temperature above 35 degrees C. The
      novelty of this study lied in incorporation of PAM Flurometry with mutagenesis to
      generate thermo-tolerant mutants of C. pyrenoidosa and investigating the reasons
      for increased yields of mutants at cellular and photosynthetic levels with the
      aim to use them for commercial biodiesel production.

PMID- 27689352
TI  - Shift in microbial community structure of anaerobic side-stream reactor in
      response to changes to anaerobic solid retention time and sludge interchange
      ratio.
AB  - A laboratory scale nutrient removal activated sludge system coupled with an
      anaerobic side-stream reactor was operated for 300 days treating real urban
      wastewater. A significant decrease in sludge production was obtained increasing
      the anaerobic solid retention time (SRTASSR) and decreasing the sludge
      interchange ratio (IR). In this study, the microbial community structure was
      analyzed and compared with the sludge reduction performance. Quantitative
      polymerase chain reaction analyses encoding 16 ribosomal RNA and functional genes
      revealed a wide diversity of phylogenetic groups in each experimental period,
      resulting from long solids retention time and recirculation of sludge under
      aerobic, anoxic and anaerobic conditions. However, decreasing SRTASSR from 10 to
      2.5d and increasing IR from 27 to 100%, an increasing selection of both
      fermenting bacteria able to release extracellular polymeric substances and
      hydrolyze organic matter and slow growing bacteria involved in nutrient removal
      were detected and linked to the sludge reduction mechanisms.

PMID- 27689353
TI  - Rapid and visual Chlamydia trachomatis detection using loop-mediated isothermal
      amplification and hydroxynaphthol blue.
AB  - : We developed an assay comprising crude DNA lysis by simple heat treatment
      coupled loop-mediated isothermal amplification with hydroxynaphthol blue for
      Chlamydia trachomatis detection (petty patent pending), and evaluated the
      developed assay for its feasibility as a one-step point-of-care detection on 284
      endocervical swab specimens from clinically symptomatic C. trachomatis and
      healthy subjects. This assay is sensitive to 0.04 pg of ompA, specific with six
      primers targeting C. trachomatis ompA region, rapid (45 min total assay time),
      inexpensive (approx. 3 USD/reaction), does not require sophisticated
      instrumentation, and has comparable assay effectiveness (95% specificity, 90-100%
      sensitivity) to bacterial DNA isolation by a commercial kit coupled with
      polymerase chain reaction and gel electrophoresis (98-100% specificity, 87-100%
      sensitivity) based on the clinical samples test. The test result could be read by
      naked eye through the colour change from violet (negative) to sky blue (positive)
      for C. trachomatis-infected specimens. Further, this assay uses all safe chemical
      reagents and is hence safe to the users. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Chlamydia trachomatis is the major bacterial sexually transmitted disease
      worldwide. The clinical symptoms are broad, and chronic C. trachomatis infections
      could lead to blindness, ectopic pregnancy, sterility in males and females, and a
      higher risk of the development of cervical cancer. The result indicates the
      potential usefulness of our crude DNA lysis coupled loop-mediated isothermal
      amplification with hydroxynaphthol blue for a simple, rapid, specific, sensitive
      and cost-effective assay for C. trachomatis detection from suspected specimens.
      This assay offers an alternative in the clinical diagnosis of C. trachomatis in
      resource-limited health-care facilities and clinical laboratories in developing
      countries, and in field tests.

PMID- 27689354
TI  - Suitability Analysis and Projected Climate Change Impact on Banana and Coffee
      Production Zones in Nepal.
AB  - The Government of Nepal has identified opportunities in agricultural
      commercialization, responding to a growing internal demand and expansion of
      export markets to reduce the immense trade deficit. Several cash crops, including
      coffee and bananas, have been identified in the recently approved Agriculture
      Development Strategy. Both of these crops have encouraged smallholder farmers to
      convert their subsistence farming practices to more commercial cultivation.
      Identification of suitable agro-ecological zones and understanding climate
      related issues are important for improved production and livelihoods of
      smallholder farmers. Here, the suitability of coffee and banana crops is analyzed
      for different agro-ecological zones represented by Global Environmental
      Stratification (GEnS). Future shifts in these suitability zones are also
      predicted. Plantation sites in Nepal were geo-referenced and used as input in
      species distribution modelling. The multi-model ensemble model suggests that
      climate change will reduce the suitable growing area for coffee by about 72%
      across the selected emission scenarios from now to 2050. Impacts are low for
      banana growing, with a reduction in suitability by about 16% by 2050. Bananas
      show a lot of potential for playing an important role in Nepal as a sustainable
      crop in the context of climate change, as this study indicates that the amount of
      area suited to banana growing will grow by 40% by 2050. Based on our analysis we
      recommend possible new locations for coffee plantations and one method for
      mitigating climate change-related problems on existing plantations. These
      findings are expected to support planning and policy dialogue for mitigation and
      support better informed and scientifically based decision-making relating to
      these two crops.

PMID- 27689355
TI  - Apo AIV and Citrulline Plasma Concentrations in Short Bowel Syndrome Patients:
      The Influence of Short Bowel Anatomy.
AB  - INTRODUCTION: Parenteral nutrition (PN) dependence in short bowel syndrome (SBS)
      patients is linked to the functionality of the remnant small bowel (RSB).
      Patients may wean off PN following a period of intestinal adaptation that
      restores this functionality. Currently, plasma citrulline is the standard
      biomarker for monitoring intestinal functionality and adaptation. However,
      available studies reveal that the relationship the biomarker with the length and
      function of the RSB is arguable. Thus, having additional biomarkers would improve
      pointing out PN weaning. AIM: By measuring concomitant changes in citrulline and
      the novel biomarker apolipoprotein AIV (Apo AIV), as well as taking into account
      the anatomy of the RSB, this exploratory study aims to a better understanding of
      the intestinal adaptation process and characterization of the SBS patients under
      PN. METHODS: Thirty four adult SBS patients were selected and assigned to adapted
      (aSBS) and non-adapted (nSBS) groups after reconstructive surgeries. Remaining
      jejunum and ileum lengths were recorded. The aSBS patients were either on an oral
      diet (ORAL group), those with intestinal insufficiency, or on oral and home
      parenteral nutrition (HPN group), those with chronic intestinal failure. Apo AIV
      and citrulline were analyzed in plasma samples after overnight fasting. An
      exploratory ROC analysis using citrulline as gold standard was performed.
      RESULTS: Biomarkers, Apo AIV and citrulline showed a significant correlation with
      RSBL in aSBS patients. In jejuno-ileocolic patients, only Apo AIV correlated with
      RSBL (rb = 0.54) and with ileum length (rb = 0.84). In patients without ileum
      neither biomarker showed any correlation with RSBL. ROC analysis indicated the
      Apo AIV cut-off value to be 4.6 mg /100 mL for differentiating between the aSBS
      HPN and ORAL groups. CONCLUSIONS: Therefore, in addition to citrulline, Apo AIV
      can be set as a biomarker to monitor intestinal adaptation in SBS patients. As
      short bowel anatomy is shown to influence citrulline and Apo AIV plasma values,
      both biomarkers complement each other furnishing a new insight to manage PN
      dependence.

PMID- 27689356
TI  - Potential Cost-Effectiveness of RSV Vaccination of Infants and Pregnant Women in
      Turkey: An Illustration Based on Bursa Data.
AB  - BACKGROUND: Worldwide, respiratory syncytial virus (RSV) is considered to be the
      most important viral cause of respiratory morbidity and mortality among infants
      and young children. Although no active vaccine is available on the market yet,
      there are several active vaccine development programs in various stages. To
      assess whether one of these vaccines might be a future asset for national
      immunization programs, modeling the costs and benefits of various vaccination
      strategies is needed. OBJECTIVES: To evaluate the potential cost-effectiveness of
      RSV vaccination of infants and/or pregnant women in Turkey. METHODS: A multi
      cohort static Markov model with cycles of one month was used to compare the cost
      effectiveness of vaccinated cohorts versus non-vaccinated cohorts. The 2014
      Turkish birth cohort was divided by twelve to construct twelve monthly birth
      cohorts of equal size (111,459 new-borns). Model input was based on clinical data
      from a multicenter prospective study from Bursa, Turkey, combined with figures
      from the (inter)national literature and publicly available data from the Turkish
      Statistical Institute (TUIK). Incremental cost-effectiveness ratios (ICERs) were
      expressed in Turkish Lira (TL) per quality-adjusted life year (QALY) gained.
      RESULTS: Vaccinating infants at 2 and 4 months of age would prevent 145,802 GP
      visits, 8,201 hospitalizations and 48 deaths during the first year of life,
      corresponding to a total gain of 1650 QALYs. The discounted ICER was estimated at
      51,969 TL (26,220 US $ in 2013) per QALY gained. Vaccinating both pregnant women
      and infants would prevent more cases, but was less attractive from a pure
      economic point of view with a discounted ICER of 61,653 TL (31,106 US $ in 2013)
      per QALY. Vaccinating only during pregnancy would result in fewer cases prevented
      than infant vaccination and a less favorable ICER. CONCLUSION: RSV vaccination of
      infants and/or pregnant women has the potential to be cost-effective in Turkey.
      Although using relatively conservative assumptions, all evaluated strategies
      remained slightly below the threshold of 3 times the GDP per capita.

PMID- 27689359
TI  - Searching for trust.

PMID- 27689358
TI  - Allatostatin A Signalling in Drosophila Regulates Feeding and Sleep and Is
      Modulated by PDF.
AB  - Feeding and sleep are fundamental behaviours with significant interconnections
      and cross-modulations. The circadian system and peptidergic signals are important
      components of this modulation, but still little is known about the mechanisms and
      networks by which they interact to regulate feeding and sleep. We show that
      specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing
      PLP neurons and enteroendocrine cells reduces feeding and promotes sleep in the
      fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA
      peptides with receptors homolog to galanin receptors subserving similar and
      apparently conserved functions in vertebrates. We further identify the PLP
      neurons as a downstream target of the neuropeptide pigment-dispersing factor
      (PDF), an output factor of the circadian clock. PLP neurons are contacted by PDF
      expressing clock neurons, and express a functional PDF receptor demonstrated by
      cAMP imaging. Silencing of AstA signalling and continuous input to AstA cells by
      tethered PDF changes the sleep/activity ratio in opposite directions but does not
      affect rhythmicity. Taken together, our results suggest that pleiotropic AstA
      signalling by a distinct neuronal and enteroendocrine AstA cell subset adapts the
      fly to a digestive energy-saving state which can be modulated by PDF.

PMID- 27689357
TI  - Fis Is Essential for Yersinia pseudotuberculosis Virulence and Protects against
      Reactive Oxygen Species Produced by Phagocytic Cells during Infection.
AB  - All three pathogenic Yersinia species share a conserved virulence plasmid that
      encodes a Type 3 Secretion System (T3SS) and its associated effector proteins.
      During mammalian infection, these effectors are injected into innate immune
      cells, where they block many bactericidal functions, including the production of
      reactive oxygen species (ROS). However, Y. pseudotuberculosis (Yptb) lacking the
      T3SS retains the ability to colonize host organs, demonstrating that chromosome
      encoded factors are sufficient for growth within mammalian tissue sites.
      Previously we uncovered more than 30 chromosomal factors that contribute to
      growth of T3SS-deficient Yptb in livers. Here, a deep sequencing-based approach
      was used to validate and characterize the phenotype of 18 of these genes during
      infection by both WT and plasmid-deficient Yptb. Additionally, the fitness of
      these mutants was evaluated in immunocompromised mice to determine whether any
      genes contributed to defense against phagocytic cell restriction. Mutants
      containing deletions of the dusB-fis operon, which encodes the nucleoid
      associated protein Fis, were markedly attenuated in immunocompetent mice, but
      were restored for growth in mice lacking neutrophils and inflammatory monocytes,
      two of the major cell types responsible for restricting Yersinia infection. We
      determined that Fis was dispensable for secretion of T3SS effectors, but was
      essential for resisting ROS and regulated the transcription of several ROS
      responsive genes. Strikingly, this protection was critical for virulence, as
      growth of DeltadusB-fis was restored in mice unable to produce ROS. These data
      support a model in which ROS generated by neutrophils and inflammatory monocytes
      that have not been translocated with T3SS effectors enter bacterial cells during
      infection, where their bactericidal effects are resisted in a Fis-dependent
      manner. This is the first report of the requirement for Fis during Yersinia
      infection and also highlights a novel mechanism by which Yptb defends against ROS
      in mammalian tissues.

PMID- 27689360
TI  - Clinical significance and prognostic value of TRIM24 expression in esophageal
      squamous cell carcinoma.
AB  - Tripartite motif-containing 24 (TRIM24), a member of the transcription
      intermediary factor 1 family, is defined as a co-regulator with several nuclear
      receptors, such as RARalpha. TRIM24 has been reported to be involved in many
      cancers. In this study, we aimed to investigate the expression pattern and
      prognostic significance of TRIM24 and its relationship with RARalpha in
      esophageal squamous cell cancer (ESCC). Both mRNA and protein expression levels
      of TRIM24 were found to be significantly decreased in ESCC, as judged by qRT-PCR
      and western blot. Immunohistochemistry staining shows that the reduced TRIM24
      protein is associated with lymph node metastasis (P=0.024), advance pathological
      TNM (pTNM) stage (P=0.046) and recurrence/metastasis (P=0.001). Upregulated
      TRIM24 protein predicts longer overall survival and disease-free survival (both
      P<0.001) and is an independent predictor for good prognosis (HR, 0.519; 95%CI,
      0.341-0.788; P=0.002). TRIM24 expression has been proven remarkably to improve
      prediction of survival of pTNM stage in ESCC patients, especially in stage I and
      II. However, no significant relationship was found between TRIM24 and RARalpha
      expression levels. In conclusion, reduced TRIM24 protein is associated with poor
      survival in ESCC patients, suggesting TRIM24 protein is a potential prognostic
      biomarker for ESCC.

PMID- 27689361
TI  - The Edge of Stability: Response Times and Delta Oscillations in Balanced
      Networks.
AB  - The standard architecture of neocortex is a network with excitation and
      inhibition in closely maintained balance. These networks respond fast and with
      high precision to their inputs and they allow selective amplification of
      patterned signals. The stability of such networks is known to depend on balancing
      the strengths of positive and negative feedback. We here show that a second
      condition is required for stability which depends on the relative strengths and
      time courses of fast (AMPA) and slow (NMDA) currents in the excitatory
      projections. This condition also determines the response time of the network. We
      show that networks which respond quickly to an input are necessarily close to an
      oscillatory instability which resonates in the delta range. This instability
      explains the existence of neocortical delta oscillations and the emergence of
      absence epilepsy. Although cortical delta oscillations are a network-level
      phenomenon, we show that in non-pathological networks, individual neurons receive
      sufficient information to keep the network in the fast-response regime without
      sliding into the instability.

PMID- 27689362
TI  - Stochastic Optimization for an Analytical Model of Saltwater Intrusion in Coastal
      Aquifers.
AB  - The present study implements a stochastic optimization technique to optimally
      manage freshwater pumping from coastal aquifers. Our simulations utilize the well
      known sharp interface model for saltwater intrusion in coastal aquifers together
      with its known analytical solution. The objective is to maximize the total volume
      of freshwater pumped by the wells from the aquifer while, at the same time,
      protecting the aquifer from saltwater intrusion. In the direction of dealing with
      this problem in real time, the ALOPEX stochastic optimization method is used, to
      optimize the pumping rates of the wells, coupled with a penalty-based strategy
      that keeps the saltwater front at a safe distance from the wells. Several
      numerical optimization results, that simulate a known real aquifer case, are
      presented. The results explore the computational performance of the chosen
      stochastic optimization method as well as its abilities to manage freshwater
      pumping in real aquifer environments.

PMID- 27689363
TI  - TCCC Updates: TCCC Abstracts.

PMID- 27689364
TI  - TacMed Updates: TEMS v. 2014.

PMID- 27689365
TI  - C-TECC Update.

PMID- 27689366
TI  - TCCC Updates: Committee on Tactical Combat Casualty Care Meeting Minutes. Davis
      Conference Center, MacDill AFB, Fl 4-5 February 2014.

PMID- 27689367
TI  - TacMed Updates: Development of a National Consensus for Tactical Emergency
      Medical Support (TEMS) Training Programs-Operators and Medical Providers.

PMID- 27689368
TI  - Committee for Tactical Emergency Casualty Care (CoTECC) Update: Summer 2014.

PMID- 27689369
TI  - TCCC Updates.

PMID- 27689370
TI  - TacMed Updates: Committee for Tactical Emergency Casualty Care (C-TECC) Update:
      Summer 2014.

PMID- 27689372
TI  - TCCC Updates: Tactical Combat Casualty Care Curriculum Annual Update 2014.

PMID- 27689371
TI  - Committee for Tactical Emergency Casualty Care (C-TECC) Update: Fall 2014.
AB  - The Johns Hopkins Center for Law Enforcement Medicine and Division of Special
      Operations in Baltimore generously hosted the June 2014 Committee for Tactical
      Emergency Casualty Care meeting (C-TECC). The C-TECC meeting focused on several
      critical issues including guideline updates, review of C-TECC member involvement
      in recent federal efforts regarding active violent incidents, examination of
      national best practices, and new partnership agreements.

PMID- 27689373
TI  - TacMed Updates: Tactical Emergency Casualty Care (TECC) Update: Winter 2014.

PMID- 27689375
TI  - TacMed Updates: Spring Committee for Tactical Emergency Casualty Care (C-TECC)
      Update.

PMID- 27689376
TI  - TCCC Updates: Committee on Tactical Combat Casualty Care Meeting: 3-4 February
      2014, Atlanta, Georgia. Meeting Minutes: 17 April 2015.

PMID- 27689374
TI  - TCCC Updates: CoTCCC Meeting 3-4 February 2015 Atlanta, Georgia.
AB  - Selected Meeting Highlights.

PMID- 27689378
TI  - TCCC Updates: Tactical Combat Casualty Care Guidelines for Medical Personnel: 3
      June 2015.

PMID- 27689377
TI  - TacMed Updates: The Committee for Tactical Emergency Casualty Care (C-TECC):
      Summer Update.

PMID- 27689379
TI  - TCCC Updates: Translating Military Advances in Exdternal Hemorrhage Control to
      Law Enforcement.

PMID- 27689381
TI  - TCCC Updates.

PMID- 27689380
TI  - TacMed Updates: Building Community Resilience to Dynamic Mass Casualty Incidents:
      A Multiagency White Paper in Support of the First Care Provider.

PMID- 27689382
TI  - Tactical Combat Casualty Care: Top Lessons for Civilian EMS Systems from 14 Years
      of War.

PMID- 27689383
TI  - Committee on Tactical Combat Casualty Care Meeting. 2-3 February 2016, Atlanta,
      Georgia: Meeting Minutes.

PMID- 27689384
TI  - Proceedings of the 2016 Spring/Summer Meeting of the Committee for Tactical
      Emergency Casualty Care.

PMID- 27689385
TI  - High-Efficiency Fog Collector: Water Unidirectional Transport on Heterogeneous
      Rough Conical Wires.
AB  - An artificial periodic roughness-gradient conical copper wire (PCCW) can be
      fabricated by inspiration from cactus spines and wet spider silks. PCCW can
      harvest fog on periodic points of the conical surface from air and transports the
      drops for a long distance without external force, which is attributed to dynamic
      as-released energy generated from drop deformation in drop coalescence, in
      addition to both gradients of geometric curve (inducing Laplace pressure) and
      periodic roughness (inducing surface energy difference). It is found that the
      ability of fog collection can be related to various tilt-angle wires, thus a fog
      collector with an array system of PCCWs is further designed to achieve a
      continuous process of efficient water collection. As a result, the effect of
      water collection on PCCWs is better than previous results. These findings are
      significant to develop and design materials with water collection and water
      transport for promising application in fogwater systems to ease the water crisis.

PMID- 27689387
TI  - Comparative Mammalian Cell Cytotoxicity of Wastewaters for Agricultural Reuse
      after Ozonation.
AB  - Reusing wastewater in agriculture is becoming increasingly common, which
      necessitates disinfection to ensure reuse safety. However, disinfectants can
      react with wastewater constituents to form disinfection byproducts (DBPs), many
      of which are toxic and restrict the goal of safe reuse. Our objective was to
      benchmark the induction of mammalian cell cytotoxicity after ozonation against
      chlorination for three types of real wastewaters: municipal secondary effluent
      and two sources of minimally treated swine farm wastewaters. A new method to
      evaluate samples of suspected high cytotoxicity was devised. For the secondary
      effluent, ozonation reduced the cytotoxicity by as much as 10 times; chlorination
      lowered the cytotoxicity only when followed by dechlorination. The swine farm
      wastewaters were up to 2000 times more cytotoxic than the secondary effluent, and
      the highest reduction in cytotoxicity was 17 times as achieved by ozonation.
      These results indicate that secondary effluent is preferred over swine
      wastewaters for agricultural reuse regardless of the tested disinfectants.
      Ozonation consistently reduced the cytotoxicity of both the full strength and the
      organic extracts of all tested wastewaters more than chlorination. The only
      significant correlation was observed in the secondary wastewater between total
      haloacetonitriles and cytotoxicity. While the association of reduced toxicity
      with the modification or reduction of specific compound(s) is unclear, regulated
      DBPs may not be the primary forcing agents.

PMID- 27689386
TI  - Copolymer Brush-Based Ultralow-Fouling Biorecognition Surface Platform for Food
      Safety.
AB  - Functional polymer coatings that combine the ability to resist nonspecific
      fouling from complex media with high biorecognition element (BRE) immobilization
      capacity represent an emerging class of new functional materials for a number of
      bioanalytical and biosensor technologies for medical diagnostics, security, and
      food safety. Here, we report on a random copolymer brush surface - poly(CBMAA-ran
      HPMAA) - providing high BRE immobilization capacity while simultaneously
      exhibiting ultralow-fouling behavior in complex food media. We demonstrate that
      both the functionalization and fouling resistance capabilities of such copolymer
      brushes can be tuned by changing the surface contents of the two monomer units:
      nonionic N-(2-hydroxypropyl) methacrylamide (HPMAA) and carboxy-functional
      zwitterionic carboxybetaine methacrylamide (CBMAA). It is demonstrated that the
      resistance to fouling decreases with the surface content of CBMAA; poly(CBMAA-ran
      HPMAA) brushes with CBMAA molar content up to 15 mol % maintain excellent
      resistance to fouling from a variety of homogenized foods (hamburger, cucumber,
      milk, and lettuce) even after covalent attachment of BREs to carboxy groups of
      CBMAA. The poly(CBMAA 15 mol %-ran-HPMAA) brushes functionalized with antibodies
      are demonstrated to exhibit fouling resistance from food samples by up to 3
      orders of magnitude better when compared with the widely used low-fouling carboxy
      functional oligo(ethylene glycol) (OEG)-based alkanethiolate self-assembled
      monolayers (AT SAMs) and, furthermore, by up to 2 orders of magnitude better when
      compared with the most successful ultralow-fouling biorecognition coatings -
      poly(carboxybetaine acrylamide), poly(CBAA). When model SPR detections of food
      borne bacterial pathogens in homogenized foods are used, it is also demonstrated
      that the antibody-functionalized poly(CBMAA 15 mol %-ran-HPMAA) brush exhibits
      superior biorecognition properties over the poly(CBAA).

PMID- 27689388
TI  - First-in-Class Chemical Probes against Poly(ADP-ribose) Glycohydrolase (PARG)
      Inhibit DNA Repair with Differential Pharmacology to Olaparib.
AB  - The enzyme poly(ADP-ribose) glycohydrolase (PARG) performs a critical role in the
      repair of DNA single strand breaks (SSBs). However, a detailed understanding of
      its mechanism of action has been hampered by a lack of credible, cell-active
      chemical probes. Herein, we demonstrate inhibition of PARG with a small molecule,
      leading to poly(ADP-ribose) (PAR) chain persistence in intact cells. Moreover, we
      describe two advanced, and chemically distinct, cell-active tool compounds with
      convincing on-target pharmacology and selectivity. Using one of these tool
      compounds, we demonstrate pharmacology consistent with PARG inhibition. Further,
      while the roles of PARG and poly(ADP-ribose) polymerase (PARP) are closely
      intertwined, we demonstrate that the pharmacology of a PARG inhibitor differs
      from that observed with the more thoroughly studied PARP inhibitor olaparib. We
      believe that these tools will facilitate a wider understanding of this important
      component of DNA repair and may enable the development of novel therapeutic
      agents exploiting the critical dependence of tumors on the DNA damage response
      (DDR).

PMID- 27689390
TI  - NaCl-Dependent Ordering and Dynamic Mechanical Response in Nanoconfined Water.
AB  - Understanding the dynamics of water under nanoscale confinement is important for
      biology, geology, tribology, and nanotechnology. In many naturally occurring
      situations, ions are present in water at various concentrations. Here we report
      on how the addition of sodium ions alters the squeeze-out behavior of water
      nanoconfined between a mica surface and silicon oxide tip. We find that Na+ ions
      enhance molecular ordering and lead to longer mechanical relaxation times. We
      also observed a critical ion concentration, above which the confined water
      switches from a viscous to an elastic (solid-like) response at very slow,
      quasistatic compression speeds.

PMID- 27689389
TI  - Room-Temperature Micron-Scale Exciton Migration in a Stabilized Emissive
      Molecular Aggregate.
AB  - We report 1.6 +/- 1 MUm exciton transport in self-assembled supramolecular light
      harvesting nanotubes (LHNs) assembled from amphiphillic cyanine dyes. We
      stabilize LHNs in a sucrose glass matrix, greatly reducing light and oxidative
      damage and allowing the observation of exciton-exciton annihilation signatures
      under weak excitation flux. Fitting to a one-dimensional diffusion model, we find
      an average exciton diffusion constant of 55 +/- 20 cm2/s, among the highest
      measured for an organic system. We develop a simple model that uses cryogenic
      measurements of static and dynamic energetic disorder to estimate a diffusion
      constant of 32 cm2/s, in agreement with experiment. We ascribe large exciton
      diffusion lengths to low static and dynamic energetic disorder in LHNs. We argue
      that matrix-stabilized LHNS represent an excellent model system to study coherent
      excitonic transport.

PMID- 27689391
TI  - Dependence of Adenine Raman Spectrum on Excitation Laser Wavelength: Comparison
      between Experiment and Theoretical Simulations.
AB  - We acquired the Raman spectra of adenine in powder and aqueous phase using
      excitation lasers with 532, 633, and 785 nm wavelengths for the region between
      300 and 1500 cm-1. In comparison to the most distinct peak at 722 cm-1, the peaks
      between 1200 and 1500 cm-1 exhibited a characteristic increase in cross-section
      with decreasing excitation wavelength in both phases. This trend can be
      reproduced by different density functional theory (DFT) calculations for the
      adenine molecule in the gas phase as well as in the aqueous phase. Furthermore,
      from the calculation on the pi-stacked dimer, hydrogen-bonded dimer, and trimer,
      we find that this trend toward excitation laser wavelength is not sensitive to
      the packing. When comparing the Raman spectra given by different excitation
      wavelength, one should take care in analyzing the cross-section, and present day
      DFT calculations are able to capture general trends in the excitation laser
      wavelength dependence of the Raman activity.

PMID- 27689392
TI  - Self-Protection Mechanism of Hexagonal WO3-Based DeNOx Catalysts against Alkali
      Poisoning.
AB  - A good catalyst for efficiently controlling NOx emissions often demands strong
      resistance against alkali poisoning. Although the traditional ion-exchange model,
      based on acid-base reactions of alkalis with Bronsted acid sites, has been
      established over the past two decades, it is difficult to be used as a guideline
      to develop such an alkali-resistant catalyst. Here we establish a self-protection
      mechanism of deNOx catalysts against alkali poisoning by systematically studying
      the intrinsic nature of alkali resistance of V2O5/HWO (HWO = hexagonal WO3) that
      shows excellent resistance to alkali poisoning in selective catalytic reduction
      of NOx with NH3 (SCR). Synchrotron X-ray diffraction and absorption
      spectroscopies demonstrate that V2O5/HWO has spatially separated catalytically
      active sites (CASs) and alkali-trapping sites (ATSs). During the SCR process,
      ATSs spontaneously trap alkali ions such as K+, even if alkali ions initially
      block CASs, thus releasing CASs to realize the self-protection against alkali
      poisoning. X-ray photoelectron spectra coupled with theoretical calculations
      indicate that the electronic interaction between the alkali ions and ATSs with an
      energy saving is the driving force of the self-protection. This work provides a
      strategy to design alkali-resistant deNOx catalysts.

PMID- 27689393
TI  - Computational Modeling of beta-Secretase 1 (BACE-1) Inhibitors Using Ligand Based
      Approaches.
AB  - The binding affinities (IC50) reported for diverse structural and chemical
      classes of human beta-secretase 1 (BACE-1) inhibitors in literature were modeled
      using multiple in silico ligand based modeling approaches and statistical
      techniques. The descriptor space encompasses simple binary molecular fingerprint,
      one- and two-dimensional constitutional, physicochemical, and topological
      descriptors, and sophisticated three-dimensional molecular fields that require
      appropriate structural alignments of varied chemical scaffolds in one universal
      chemical space. The affinities were modeled using qualitative classification or
      quantitative regression schemes involving linear, nonlinear, and deep neural
      network (DNN) machine-learning methods used in the scientific literature for
      quantitative-structure activity relationships (QSAR). In a departure from
      tradition, ~20% of the chemically diverse data set (205 compounds) was used to
      train the model with the remaining ~80% of the structural and chemical analogs
      used as part of an external validation (1273 compounds) and prospective test (69
      compounds) sets respectively to ascertain the model performance. The machine
      learning methods investigated herein performed well in both the qualitative
      classification (~70% accuracy) and quantitative IC50 predictions (RMSE ~ 1 log).
      The success of the 2D descriptor based machine learning approach when compared
      against the 3D field based technique pursued for hBACE-1 inhibitors provides a
      strong impetus for systematically applying such methods during the lead
      identification and optimization efforts for other protein families as well.

PMID- 27689394
TI  - Water Rearrangements upon Disorder-to-Order Amyloid Transition.
AB  - Water plays a critical role in governing the intricate balance between chain
      chain and chain-solvent interactions during protein folding, misfolding, and
      aggregation. Previous studies have indicated the presence of different types of
      water in folded (globular) proteins. In this work, using femtosecond and
      picosecond time-resolved fluorescence measurements, we have characterized the
      solvation dynamics from ultrafast to ultraslow time scale both in the monomeric
      state and in the amyloid state of an intrinsically disordered protein, namely
      kappa-casein. Monomeric kappa-casein adopts a compact disordered state under
      physiological conditions and is capable of spontaneously aggregating into highly
      ordered beta-rich amyloid fibrils. Our results indicate that the mobility of
      "biological water" (type I) gets restrained as a result of conformational
      sequestration during amyloid formation. Additionally, a significant decrease in
      the bulk water component with a concomitant increase in the ultraslow component
      revealed the ordering of trapped interstitial water (type II) upon disorder-to
      order amyloid transition. Our results provide an experimental underpinning of
      significant water rearrangements associated with both chain desolvation and water
      confinement upon amyloid formation.

PMID- 27689395
TI  - Public Health Stops at the School House Door.

PMID- 27689396
TI  - Prognostic nomogram for previously untreated adult patients with acute myeloid
      leukemia.
AB  - This study was designed to perform an acceptable prognostic nomogram for acute
      myeloid leukemia. The clinical data from 311 patients from our institution and
      165 patients generated with Cancer Genome Atlas Research Network were reviewed. A
      prognostic nomogram was designed according to the Cox's proportional hazard model
      to predict overall survival (OS). To compare the capacity of the nomogram with
      that of the current prognostic system, the concordance index (C-index) was used
      to validate the accuracy as well as the calibration curve. The nomogram included
      6 valuable variables: age, risk stratifications based on cytogenetic
      abnormalities, status of FLT3-ITD mutation, status of NPM1 mutation, expression
      of CD34, and expression of HLA-DR. The C-indexes were 0.71 and 0.68 in the
      primary and validation cohort respectively, which were superior to the predictive
      capacity of the current prognostic systems in both cohorts. The nomogram allowed
      both patients with acute myeloid leukemia and physicians to make prediction of OS
      individually prior to treatment.

PMID- 27689398
TI  - Comparative effectiveness of image-guided radiotherapy for non-operated localized
      esophageal squamous cell carcinoma patients receiving concurrent
      chemoradiotherapy: A population-based propensity score matched analysis.
AB  - BACKGROUND: Although concurrent chemoradiotherapy (CCRT) coupled with image
      guided radiotherapy (IGRT) is associated with a theoretical benefit in non
      operated localized esophageal squamous cell carcinoma (NOL-ESCC) patients, there
      is currently no clinical evidence to support this. RESULTS: The study population
      in the primary analysis comprised 866 patients who were well balanced in terms of
      their co-variables. The HR for mortality when group A was compared with group B
      was 0.82 (95% confidence interval, 0.7-0.95). SA revealed that the result was
      moderately sensitive. MATERIALS AND METHODS: Eligible patients diagnosed between
      2008 and 2013 were identified in the Taiwan Cancer Registry. A propensity score
      matched cohort was constructed [1:1 in groups A (with IGRT) and B (without IGRT)]
      to balance any observable potential confounders. The hazard ratio (HR) for
      mortality was compared between groups A and B during the follow-up period.
      Sensitivity analyses (SA) were performed to evaluate the robustness of the
      findings regarding the selection of confounders and a potential unobserved
      confounder. CONCLUSIONS: The current results provide the first clinical evidence
      that CCRT coupled with IGRT is associated with better overall survival when
      compared with CCRT without IGRT in NOL-ESCC patients. However, this study should
      be interpreted with caution given its non-randomized nature and the moderate
      sensitivity of the data. Further studies are needed to clarify this finding.

PMID- 27689397
TI  - A CD22-reactive TCR from the T-cell allorepertoire for the treatment of acute
      lymphoblastic leukemia by TCR gene transfer.
AB  - CD22 is currently evaluated as a target-antigen for the treatment of B-cell
      malignancies using chimeric antigen receptor (CAR)-engineered T-cells or
      monoclonal antibodies (mAbs). CAR- and mAbs-based immunotherapies have been
      successfully applied targeting other antigens, however, occurrence of refractory
      disease to these interventions urges the identification of additional strategies.
      Here, we identified a TCR recognizing the CD22-derived peptide RPFPPHIQL
      (CD22RPF) presented in human leukocyte antigen (HLA)-B*07:02. To overcome
      tolerance to self-antigens such as CD22, we exploited the immunogenicity of
      allogeneic HLA. CD22RPF-specific T-cell clone 9D4 was isolated from a healthy HLA
      B*07:02neg individual, efficiently produced cytokines upon stimulation with
      primary acute lymphoblastic leukemia and healthy B-cells, but did not react
      towards healthy hematopoietic and nonhematopoietic cell subsets, including
      dendritic cells (DCs) and macrophages expressing low levels of CD22. Gene
      transfer of TCR-9D4 installed potent CD22-specificity onto recipient CD8+ T-cells
      that recognized and lysed primary B-cell leukemia. TCR-transduced T-cells spared
      healthy CD22neg hematopoietic cell subsets but weakly lysed CD22low-expressing
      DCs and macrophages. CD22-specific TCR-engineered T-cells could form an
      additional immunotherapeutic strategy with a complementary role to CAR- and
      antibody-based interventions in the treatment of B-cell malignancies. However,
      CD22 expression on non-B-cells may limit the attractiveness of CD22 as target
      antigen in cellular immunotherapy.

PMID- 27689399
TI  - Epigenetic silencing of tumor suppressor long non-coding RNA BM742401 in chronic
      lymphocytic leukemia.
AB  - BM742401 is a tumor suppressor lncRNA downregulated in gastric cancer. As the
      promoter region and the entire transcript are embedded in a CpG island, we
      postulated that BM742401 is a tumor suppressor lncRNA inactivated by DNA
      methylation in chronic lymphocytic leukemia (CLL). The promoter of BM742401 was
      unmethylated in normal controls including three each of normal bone marrow,
      peripheral blood buffy coats, and CD19-sorted peripheral B-cells, but methylated
      in four (57.1%) CLL cell lines. Methylation of BM742401 correlated inversely with
      expression. In the completely methylated WAC3CD5+ CLL cells, 5-Aza-2'
      deoxycytidine treatment led to promoter demethylation and re-expression of
      BM742401 transcript. Functionally, stable overexpression of BM742401 resulted in
      inhibition of cellular proliferation and enhanced apoptosis through caspase-9
      dependent intrinsic but not caspase-8-dependent extrinsic apoptosis pathway,
      suggesting a tumor suppressor role of BM742401 in CLL. In primary CLL samples,
      methylation of BM742401 was detected in 43/98 (43.9%) of patients. Moreover,
      among CLL patients with standard-risk cytogenetic aberrations, methylation of
      BM742401 correlated with advanced Rai stage (>= stage 2)(P = 0.002). Furthermore,
      BM742401 methylation was associated with miR-129-2 methylation (P = 0.05).
      BM742401 is a tumor suppressor lncRNA frequently methylated in CLL. The mechanism
      of BM742401 as a tumor suppressor warrants further studies.

PMID- 27689400
TI  - Long noncoding RNA uc.345 promotes tumorigenesis of pancreatic cancer by
      upregulation of hnRNPL expression.
AB  - Increasing evidence points to an important functional or regulatory role of long
      noncoding RNA in cellular processes as well as cancer diseases resulted from the
      aberrant lncRNA expression. LncRNA could participate in the cancer progression
      and develop a significant role through the interaction with proteins. In the
      present study, we report a lncRNA termed uc.345 that is up-regulated in tumor
      tissues, compared to the corresponding noncancerous tissues. We found that a
      higher uc.345 expression level was more frequently observed in tissues with
      increased depth of invasion and advanced TNM tumor node metastasis T stage.
      Moreover, uc.345 could be used as an independent risk factor for the overall
      survival (OS) of the pancreatic cancer patients. By employing soft agar assays
      and tumor xenograft models, we showed that uc.345 could accelerate tumor growth.
      Further, we discovered that uc.345 could upregulate the hnRNPL expression and
      that inhibition of (hnRNPL) dampens the tumorigenesis capability of uc.345.
      Collectively, these results demonstrate that uc.345 functions as an oncogenic
      lncRNA that promotes tumor progression and serves as a poor predictor for
      pancreatic cancer patients' overall survival.

PMID- 27689401
TI  - Expression of the TPalpha and TPbeta isoforms of the thromboxane prostanoid
      receptor (TP) in prostate cancer: clinical significance and diagnostic potential.
AB  - The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is
      increasingly implicated in cancer progression. TXA2 signals through two T
      Prostanoid receptor (TP) isoforms termed TPalpha and TPbeta, with both encoded by
      the TBXA2R gene. Despite exhibiting several functional and regulatory
      differences, the role of the individual TP isoforms in neoplastic diseases is
      largely unknown.This study evaluated expression of the TPalpha and TPbeta
      isoforms in tumour microarrays of the benign prostate and different pathological
      (Gleason) grades of prostate cancer (PCa). Expression of TPbeta was significantly
      increased in PCa relative to benign tissue and strongly correlated with
      increasing Gleason grade. Furthermore, higher TPbeta expression was associated
      with increased risk of biochemical recurrence (BCR) and significantly shorter
      disease-free survival time in patients post-surgery. While TPalpha was more
      variably expressed than TPbeta in PCa, increased/high TPalpha expression within
      the tumour also trended toward increased BCR and shorter disease-free survival
      time. Comparative genomic CpG DNA methylation analysis revealed substantial
      differences in the extent of methylation of the promoter regions of the TBXA2R
      that specifically regulate expression of TPalpha and TPbeta, respectively, both
      in benign prostate and in clinically-derived tissue representative of precursor
      lesions and progressive stages of PCa. Collectively, TPalpha and TPbeta
      expression is differentially regulated both in the benign and tumourigenic
      prostate, and coincides with clinical pathology and altered CpG methylation of
      the TBXA2R gene. Analysis of TPbeta, or a combination of TPalpha/TPbeta,
      expression levels may have significant clinical potential as a diagnostic
      biomarker and predictor of PCa disease recurrence.

PMID- 27689402
TI  - Integration of zebrafish fin regeneration genes with expression data of human
      tumors in silico uncovers potential novel melanoma markers.
AB  - Tissue regeneration requires expression of a large, unknown number of genes to
      initiate and maintain cellular processes such as proliferation, extracellular
      matrix synthesis, differentiation and migration. A unique model to simulate this
      process in a controlled manner is the re-growth of the caudal fin of zebrafish
      after amputation. Within this tissue stem cells differentiate into fibroblasts,
      epithelial and endothelial cells as well as melanocytes. Many genes implicated in
      the regeneration process are deregulated in cancer. We therefore undertook a
      systematic gene expression study to identify genes upregulated during the re
      growth of caudal fin tissue. By applying a high stringency cut-off value of 4
      fold change, we identified 54 annotated genes significantly overexpressed in
      regenerating blastema. Further bioinformatics data mining studies showed that 22
      out of the 54 regeneration genes where overexpressed in melanoma compared to
      normal skin or other cancers. Whereas the role of TNC (tenascin C) and FN1
      (fibronectin 1) in melanoma development is well documented, implication of
      MARCKS, RCN3, BAMBI, PEA3/ETV4 and the FK506 family members FKBP7, FKBP10 and
      FKBP11 in melanoma progression is unclear. Corresponding proteins were detected
      in melanoma tissue but not in normal skin. High expression of FKBP7, DPYSL5 and
      MDK was significantly associated with poor survival. We discuss a potential role
      of these novel melanoma genes, which have promising potential as new therapeutic
      targets or diagnostic markers.

PMID- 27689404
TI  - In vivo phage display screening for tumor vascular targets in glioblastoma
      identifies a llama nanobody against dynactin-1-p150Glued.
AB  - Diffuse gliomas are primary brain cancers that are characterised by infiltrative
      growth. Whereas high-grade glioma characteristically presents with perinecrotic
      neovascularisation, large tumor areas thrive on pre-existent vasculature as well.
      Clinical studies have revealed that pharmacological inhibition of the angiogenic
      process does not improve survival of glioblastoma patients. Direct targeting of
      tumor vessels may however still be an interesting therapeutic approach as it
      allows pinching off the blood supply to tumor cells. Such tumor vessel targeting
      requires the identification of tumor-specific vascular targeting agents
      (TVTAs).Here we describe a novel TVTA, C-C7, which we identified via in vivo
      biopanning of a llama nanobody phage display library in an orthotopic mouse model
      of diffuse glioma. We show that C-C7 recognizes a subpopulation of tumor blood
      vessels in glioma xenografts and clinical glioma samples. Additionally, C-C7
      recognizes macrophages and activated endothelial cells in atherosclerotic
      lesions. By using C-C7 as bait in yeast-2-hybrid (Y2H) screens we identified
      dynactin-1-p150Glued as its binding partner. The interaction was confirmed by co
      immunostainings with C-C7 and a commercial anti-dynactin-1-p150Glued antibody,
      and via co-immunoprecipitation/western blot studies. Normal brain vessels do not
      express dynactin-1-p150Glued and its expression is reduced under anti-VEGF
      therapy, suggesting that dynactin-1-p150Glued is a marker for activated
      endothelial cells.In conclusion, we show that in vivo phage display combined with
      Y2H screenings provides a powerful approach to identify tumor-targeting
      nanobodies and their binding partners. Using this combination of methods we
      identify dynactin-1-p150Glued as a novel targetable protein on activated
      endothelial cells and macrophages.

PMID- 27689405
TI  - Progressive changes in composition of lymphocytes in lung tissues from patients
      with non-small-cell lung cancer.
AB  - Immune cell infiltration is a common feature of many human solid tumors. Innate
      and adaptative immune systems contribute to tumor immunosurveillance. We
      investigated whether tumors evade immune surveillance by inducing states of
      tolerance and/or through the inability of some immune subpopulations to
      effectively penetrate tumor nests. Immunohistochemistry and flow cytometry
      analysis were used to study the composition and distribution of immune
      subpopulations in samples of peripheral blood, tumor tissue (TT), adjacent tumor
      tissue (ATT), distant non-tumor tissue (DNTT), cancer nests, cancer stroma, and
      invasive margin in 61 non-small-cell lung cancer (NSCLC) patients. A
      significantly higher percentage of T and B cells and significantly lower
      percentage of NK cells were detected in TT than in DNTT. Memory T cells
      (CD4+CD45RO+, CD8+CD45RO+) and activated T cells (CD8+DR+) were more prevalent in
      TT. Alongside this immune activation, the percentage of T cells with
      immunosuppressive activity was higher in TT than in DNTT. B- cells were
      practically non-existent in tumor nests and were preferentially located in the
      invasive margin. The dominant NK cell phenotype in peripheral blood and DNTT was
      the cytotoxic phenotype (CD56+ CD16+), while the presence of these cells was
      significantly decreased in ATT and further decreased in TT. Finally, the
      immunologic response differed between adenocarcinoma and squamous cell carcinoma
      and according to the tumor differentiation grade. These findings on the
      infiltration of innate and adaptative immune cells into tumors contribute to a
      more complete picture of the immune reaction in NSCLC.

PMID- 27689403
TI  - Blockade of the Hedgehog pathway downregulates estrogen receptor alpha signaling
      in breast cancer cells.
AB  - Anti-estrogen treatment, exemplified by tamoxifen, is a well-established adjuvant
      therapy for estrogen receptor alpha (ERalpha)-positive breast cancer. However,
      the effectiveness of this drug is limited due to the development of resistance.
      The Hedgehog (HH) signaling pathway is critical in embryonic development, and
      aberrant activation of this transduction cascade is linked to various
      malignancies. However, it remains unclear whether HH signaling is activated in
      human breast cancer and related to tamoxifen resistance. Deciphering how this
      pathway may be involved in breast cancer is a crucial step towards the
      establishment of targeted combinatorial treatments for this disease. Here, we
      show that the expression of the HH signaling effector protein GLI1 is higher in
      tamoxifen resistant compared to sensitive cells. Tamoxifen resistant cells have
      stronger ERalpha transcriptional activity relative to sensitive cells, even
      though the ERalpha expression is similar in both cell types. Knockdown of GLI1
      attenuates cell proliferation and reduces ERalpha transcriptional activity in
      both sensitive and resistant cells, irrespective of estrogen stimulation.
      Combinatorial treatment of tamoxifen and the GLI antagonist GANT61 further
      suppresses the growth of sensitive and resistant cells relative to administration
      of only tamoxifen, and this was irrespective of estrogen stimulation. Moreover, a
      positive correlation between GLI1 and ERalpha expression was identified in breast
      cancer samples. Additionally, high GLI1 expression predicted worse distant
      metastasis-free survival in breast cancer patients. These data suggest that the
      HH pathway may be a new candidate for therapeutic targeting and prognosis in
      ERalpha-positive breast cancer.

PMID- 27689406
TI  - Measuring the Pharmacokinetic Properties of Drugs with a Novel Surgical Rat
      Model.
AB  - : Purpose/aim of the study: The pharmacokinetic (PK) parameters in animal models
      can help optimize novel candidate drugs prior to human trials. However, due to
      the complexity of pharmacokinetic experiments, their use is limited in academia.
      We present a novel surgical rat model for investigation of pharmacokinetic
      parameters and its use in an anti-obesity drug development program. MATERIALS AND
      METHODS: The model uses anesthetized male Wistar rats, a jugular, a femoral
      catheter, and an insulin pump for peptide infusion. The following pharmacokinetic
      parameters were measured: metabolic clearance rate (MCR), half-life, and volume
      of distribution (Vd). Glucagon-like peptide 1 (GLP-1), glucagon (GCG), and
      exendin-4 (Ex-4) were used to validate the model. The pharmacokinetic parameters
      of anti-obesity drug candidates X1, X2, and X3 were measured. RESULTS: GLP-1 had
      a significantly higher MCR (83.9 +/- 14.1 mL/min/kg) compared to GCG (40.7 +/-
      14.3 mL/min/kg) and Ex-4 (10.1 +/- 2.5 mL/min/kg) (p < .01 and p < .001
      respectively). Ex-4 had a statistically significant longer half-life (35.1 +/-
      7.4 min) compared to both GCG (3.2 +/- 1.7 min) and GLP-1 (1.2 +/- 0.4 min) (p <
      .01 for both GCG and GLP-1). Ex-4 had a statistically significant higher volume
      of distribution (429.7 +/- 164.9 mL/kg) compared to both GCG (146.8 +/- 49.6
      mL/kg) and GLP-1 (149.7 +/- 53.5 mL/kg) (p < .01 for both GCG and GLP-1). Peptide
      X3 had a statistically significant longer half-life (21.3 +/- 3.5 min) compared
      to both X1 (3.9 +/- 0.4 min) and X2 (16.1 +/- 2.8 min) (p < .001 for both X1 and
      X2). CONCLUSIONS: We present an affordable and easily accessible platform for the
      measurement of PK parameters of peptides. This novel surgical rat model produces
      consistent and reproducible results while minimizing animal use.

PMID- 27689407
TI  - Contraceptive counselling of women seeking abortion - a qualitative interview
      study of health professionals' experiences.
AB  - OBJECTIVES: A substantial proportion of women who undergo an abortion continue
      afterwards without switching to more effective contraceptive use. Many
      subsequently have repeat unintended pregnancies. This study, therefore, aimed to
      identify and describe health professionals experiences of providing contraceptive
      counselling to women seeking an abortion. METHODS: We interviewed 21 health
      professionals (HPs), involved in contraceptive counselling of women seeking
      abortion at three differently sized hospitals in Sweden. The interviews were
      recorded and transcribed verbatim and analysed using conventional qualitative
      content analysis. RESULTS: Three clusters were identified: 'Complex counselling',
      'Elements of counselling' and 'Finding a method'. HPs often experienced
      consultations including contraceptive counselling at the time of an abortion as
      complex, covering both pregnancy termination and contraceptive counselling. Women
      with vulnerabilities placed even greater demands on the HPs providing
      counselling. The HPs varied in their approaches when providing contraceptive
      counselling but also in their knowledge about certain contraception methods. HPs
      described challenges in finding out if women had found an effective method and in
      the practicalities of arranging intrauterine device (IUD) insertion post
      abortion, when a woman asked for this method. CONCLUSIONS: HPs found it
      challenging to provide contraceptive counselling at the time of an abortion and
      to arrange access to IUDs post-abortion. There is a need to improve their
      counselling, their skills and their knowledge to prevent repeat unintended
      pregnancies.

PMID- 27689408
TI  - Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ
      ophthalmic gel for sustained delivery and enhanced ocular bioavailability.
AB  - A novel cationic nanoemulsified in-situ ophthalmic gel of loteprednol etabonate
      (LE) was developed to improve the permeability and retention time of formulations
      for overall improvement of drug's ocular bioavability. Capryol 90 (oil phase),
      tween 80 (surfactant) and transcutol P (cosurfactant) was selected as formulation
      excipients to construct pseudoternary phase diagrams and nanoemulsion region was
      recognized from diagrams. Spontaneous emulsification method was used to
      manufacture LE nanoemulsion and it was optimized using 32 factorial design by
      considering the amount of oil and the ratio of surfactant to cosurfactant (Smix)
      as independent variables and evaluated for various physicochemical properties.
      Optimized NE was dispersed in Poloxamer 407 and 188 solution to form
      nanoemulsified sols that were predictable to transform into in-situ gels at
      corneal temperature. Drug pharmacokinetics of sterilized optimized in situ NE
      gel, NE-ISG2 [0.69% w/w Capryol 90, 0.99%w/w Smix (3:1), 13% Poloxamer 407, 4%
      w/w Poloxamer 188] and marketed formulation were assessed in rabbit aqueous
      humor. The in-situ gels were clear, shear thinning in nature and displayed zero
      order drug release kinetics. NE-ISG2 showed the minimum ocular irritation
      potential and significantly (p < 0.01) higher Cmax and AUC(0-10 h), delayed Tmax,
      extended mean residence time and improved (2.54-fold times) bioavailability
      compared to marketed formulation.

PMID- 27689409
TI  - Increased Metabolic Disorders and Impaired Insulin Secretory Function in the
      First-Degree Relatives of Type 2 Diabetic Patients with Normal Glucose Tolerance.
AB  - OBJECTIVE: To compare the metabolic status and pancreatic beta-cell function in
      first-degree relatives (FDRs) of type 2 diabetic patients with normal glucose
      tolerance (NGT). MATERIALS AND METHODS: Three hundred twelve subjects, who were
      NGT-FDR of type 2 diabetic patients and 1348 subjects, who were NGT individuals
      with no family history of diabetes, were defined as NGT-FDRs and NGT-controls
      (NGT-C), respectively. Blood pressure, body weight, waist circumference, plasma
      glucose, lipid profile, and insulin levels were measured in all subjects.
      Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-beta, insulin
      sensitivity index (ISI), and disposition index (DI) was used to evaluate insulin
      resistance and insulin sensitivity. RESULTS: The HOMA-IR and HOMA-beta indices
      were significantly higher in the NGT-FDR group relative to the NGT-C, while the
      ISI, DI, and DeltaI30/DeltaG30 were lower (P < 0.05). The prevalence rate of
      greater than or equal to three metabolic disorders was higher in the NGT-FDR
      group compared to the NGT-C (P < 0.05). In the NGT-FDR group, compared to people
      with normal metabolism, HOMA-beta decreased when there was only one metabolic
      disorder, increased slightly when there were two to three metabolic
      abnormalities, and decreased again when there were four or more metabolic
      abnormalities. The data also indicated that having a family history of type 2
      diabetes maybe an independent risk factor of beta-cell dysfunction. CONCLUSIONS:
      Metabolic disorders developed frequently in the NGT-FDRs of type 2 diabetic
      patients. As the number of coexisting metabolic disorders increased, pancreatic
      beta-cell secretory ability and insulin sensitivity decreased. Therefore, it is
      necessary to provide early preventive interventions and monitoring of metabolic
      indices for NGT-FDRs of type 2 diabetic patients.

PMID- 27689410
TI  - The Effects of Costaria costata Extracts on Atopic Dermatitis in an In Vitro
      Model.
AB  - We have provided a protocol for establishing an atopic dermatitis (AD) in vitro
      model, and evaluated the effects of Costaria costata (CC) extracts on AD in an in
      vitro model using keratinocytes and splenocytes from AD-induced mice and mast
      cells. HaCaT cells were each treated with 200 MUg/mL of CC water extract (CCW),
      CC 10% ethanol extract (CCE10%), and CC 70% ethanol extract (CCE70%), immediately
      followed by stimulation with 20 ng/mL tumor necrosis factor (TNF)-alpha, and 20
      ng/mL interferon (IFN)-gamma for inflammation. The splenocytes from AD-induced
      mice were each treated with 200 MUg/mL of CCW, CCE10%, and CCE70%, followed by
      stimulation with 5 MUg/mL ConA or lipopolysaccharide (LPS), to induce T cell or B
      cell activation, and 5 MUg/mL LPS and 50 ng/mL interleukin-4, to induce
      immunoglobulin (Ig) E production. We investigated the effects of CCW, CCE10%, and
      CCE70% on the production of histamine in PMA, and A23187-stimulated MC/9 cells.
      We found that treatments with CC extracts decreased the production of
      proinflammatory cytokines in TNF-alpha and IFN-gamma-stimulated HaCaT cells, and
      the suppression of the imbalance of Th1/Th2 cytokines and IgE production on
      primary splenocytes. In addition, CC extracts resulted in a decrease in histamine
      release in the PMA and A23187-simulated MC/9 cells. According to our present
      results, we can conclude that CC extracts may be effective for the treatment of
      other allergy diseases, and AD, via the attenuation of allergic reactions.

PMID- 27689412
TI  - Development and optimization of transferrin-conjugated nanostructured lipid
      carriers for brain delivery of paclitaxel using Box-Behnken design.
AB  - The treatment of brain cancer remains one of the most difficult challenges in
      oncology. The purpose of this study was to develop transferrin-conjugated
      nanostructured lipid carriers (Tf-NLCs) for brain delivery of paclitaxel (PTX).
      PTX-loaded NLCs (PTX-NLCs) were prepared using solvent evaporation method and the
      impact of various formulation variables were assessed using Box-Behnken design.
      Optimized PTX-NLC was coupled with transferrin as targeting ligand and in vitro
      cytotoxicity of it was investigated against U-87 brain cancer cell line. As a
      result, 14.1 mg of cholesterol, 18.5 mg of triolein, and 0.5% poloxamer were used
      to prepare the optimal formulation. Mean particle size (PS), zeta potential (ZP),
      entrapment efficiency (EE), drug loading (DL), mean release time (MRT) of adopted
      formulation were confirmed to be 205.4 +/- 11 nm, 25.7 +/- 6.22 mV, 91.8 +/-
      0.5%, 5.38 +/- 0.03% and 29.3 h, respectively. Following conjugation of optimized
      PTX-NLCs with transferrin, coupling efficiency was 21.3 mg transferrin per mmol
      of stearylamine; PS and MRT were increased while ZP, EE and DL decreased non
      significantly. Tf-PTX-NLCs showed higher cytotoxic activity compared to non
      targeted NLCs and free drug. These results indicated that the Tf-PTX-NLCs could
      potentially be exploited as a delivery system in brain cancer cells.

PMID- 27689413
TI  - Estrogens Exacerbate Nociceptive Pain via Up-Regulation of TRPV1 and ANO1 in
      Trigeminal Primary Neurons of Female Rats.
AB  - Several trigeminal pain disorders show sex differences, and high levels of
      estrogens may underlie these differences. The interaction between transient
      receptor potential vanilloid 1 (TRPV1) and anoctamin 1 (ANO1) plays an important
      role in peripheral nociception. However, whether TRPV1 and ANO1 are involved in
      estrogen-modulated trigeminal pain sensitivity is unclear. In this study, we
      examined estradiol (E2) modulation of nociception through behavioral and
      immunohistological experiments after application of capsaicin (Cap), a selective
      TRPV1 agonist, onto the ocular surface in ovariectomized rats treated with high
      dose E2 (HE) or low-dose E2 (LE) for 2 days. In addition, we used real-time PCR
      to study the effects of E2 on the expression levels of TRPV1 and ANO1 mRNA in
      trigeminal ganglia. In the behavioral experiment, the HE group showed significant
      potentiation of Cap-evoked nocifensive behavior compared with the LE group.
      Immunohistochemistry showed that Cap evoked a significantly greater number of
      cells that were immunoreactive for c-Fos, a marker of nociceptive activation, in
      the trigeminal subnucleus caudalis/upper cervical cord in the HE group than in
      the LE group. The number of c-Fos-immunoreactive cells in the ventral trigeminal
      interpolaris/caudalis were similar in the 2 groups. Real-time PCR showed that the
      levels of TRPV1 and ANO1 mRNA in the HE group were significantly higher than
      levels in the LE group. Thus, high levels of estrogens may be a risk factor for
      Cap-evoked nociceptive pain, and estrogen-dependent increases in TRPV1 and ANO1
      are likely involved in modulating the nociceptive response in the trigeminal
      area.

PMID- 27689414
TI  - Igf Binding Proteins Protect Undifferentiated Spermatogonia in the Zebrafish
      Testis Against Excessive Differentiation.
AB  - IGF binding proteins (IGFBPs) modulate the availability of IGFs for their cognate
      receptors. In zebrafish testes, IGF3 promotes the proliferation and
      differentiation of type A undifferentiated (Aund) spermatogonia, and igf3
      expression is strongly elevated by FSH but also responds to T3. Here we report
      the effects of FSH and T3 on igfbp transcript levels in adult zebrafish testis.
      We then examined T3 and FSH effects on zebrafish spermatogenesis and explored the
      relevance of IGFBPs in modulating these T3 or FSH effects, using a primary tissue
      culture system for adult zebrafish testis. T3 up-regulated igfbp1a and igfbp3
      expression, whereas FSH reduced igfbp1a transcript levels. To quantify effects on
      spermatogenesis, we determined the mitotic index and relative section areas
      occupied by Aund, type A differentiating, or type B spermatogonia. In general, T3
      and FSH stimulated spermatogonial proliferation and increased the areas occupied
      by spermatogonia, suggesting that both self-renewal and differentiating divisions
      were stimulated. Preventing IGF/IGFBP interaction by NBI-31772 further increased
      T3- or FSH-induced spermatogonial proliferation. However, under these conditions
      the more differentiated type A differentiating and B spermatogonia occupied
      larger surface areas at the expense of the area held by Aund spermatogonia.
      Clearly decreased nanos2 transcript levels are in agreement with this finding,
      and reduced amh expression may have facilitated spermatogonial differentiation.
      We conclude that elevating IGF3 bioactivity by blocking IGFBPs shifted T3- or FSH
      induced signaling from stimulating spermatogonial self-renewal as well as
      differentiation toward predominantly stimulating spermatogonial differentiation,
      which leads to a depletion of type Aund spermatogonia.

PMID- 27689411
TI  - Mechanisms and functions of extracellular vesicle release in vivo-What we can
      learn from flies and worms.
AB  - Cells from bacteria to man release extracellular vesicles (EVs) that contain
      signaling molecules like proteins, lipids, and nucleic acids. The content,
      formation, and signaling roles of these conserved vesicles are diverse, but the
      physiological relevance of EV signaling in vivo is still debated. Studies in
      classical genetic model organisms like C. elegans and Drosophila have begun to
      reveal the developmental and behavioral roles for EVs. In this review, we discuss
      the emerging evidence for the in vivo signaling roles of EVs. Significant effort
      has also been made to understand the mechanisms behind the formation and release
      of EVs, specifically of exosomes derived from exocytosis of multivesicular bodies
      and of microvesicles derived from plasma membrane budding called ectocytosis. In
      this review, we detail the impact of flies and worms on understanding the
      proteins and lipids involved in EV biogenesis and highlight the open questions in
      the field.

PMID- 27689415
TI  - Glucose Transporter-4 Facilitates Insulin-Stimulated Glucose Uptake in
      Osteoblasts.
AB  - Recent studies have identified the osteoblast as an insulin responsive cell that
      participates in global energy homeostasis. Here, we show that glucose transporter
      4 (Glut4) is required for insulin-dependent uptake and oxidation of glucose in
      mature osteoblasts. In primary cultures of mouse osteoblasts, insulin increased
      uptake and oxidation of 14C-glucose in a dose-dependent fashion but did not
      significantly affect uptake or oxidation of 14C-oleate. In vitro,
      undifferentiated osteoblasts expressed 3 high-affinity Gluts: Glut1, Glut4, and
      Glut3. However, although levels of Glut1 and Glut3 remained constant during the
      course of osteoblast differentiation, Glut4 expression increased by 5-fold in
      association with enhanced insulin-stimulated glucose uptake. Glut4 ablation in
      osteoblasts in vitro eliminated insulin-stimulated glucose uptake, reduced
      proliferation and diminished measures of osteoblast maturation. In vivo, Glut4
      expression was observed in osteoblasts, osteocytes, and chondrocytes at a level
      approaching that observed in adjacent skeletal muscle. To determine the
      importance of Glut4 in bone in vivo, we generated mice lacking Glut4 in
      osteoblasts and osteocytes (DeltaGlut4). DeltaGlut4 mice exhibited normal bone
      architecture but exhibited an increase in peripheral fat in association with
      hyperinsulinemia, beta-cell islet hypertrophy, and reduced insulin sensitivity.
      Surprisingly, the expression of insulin target genes in liver, muscle, and
      adipose from DeltaGlut4 mice were unchanged or increased, indicating that
      alterations in glucose homeostasis were the result of reduced clearance by bone.
      These findings suggest that Glut4 mediates insulin-stimulated glucose uptake by
      mature osteoblasts/osteocytes and that the magnitude of glucose use by bone cells
      is sufficient to impact global glucose disposal in the mouse.

PMID- 27689416
TI  - Attitudes in Patients with Autosomal Dominant Polycystic Kidney Disease Toward
      Prenatal Diagnosis and Preimplantation Genetic Diagnosis.
AB  - AIMS: No recommendations currently exist regarding implementation of both
      prenatal diagnosis and preimplantation genetic diagnosis (PGD) for autosomal
      dominant polycystic kidney disease (ADPKD). This study evaluated attitudes in
      ADPKD patients with either chronic kidney disease (CKD) stages I-IV or end-stage
      renal failure (ESRF) toward prenatal diagnosis and PGD. METHODS: Ninety-six ADPKD
      patients were recruited from an outpatient clinic, wards, and dialysis units.
      Thirty-eight patients had ESRF and 58 had CKD stages I-IV. Participants were
      given an information sheet on prenatal diagnosis and PGD and subsequently
      completed a questionnaire. RESULTS: The median age of participants was 51.5
      years. Seventeen percent of ADPKD patients with CKD and 18% of ADPKD patients
      with ESRF would consider prenatal diagnosis and termination of pregnancy for
      ADPKD. Fifty percent with CKD would have opted for PGD (or might consider it in
      the future) were it available and funded by the UK National Health Service,
      compared to 63% in the ESRF group (p = 0.33). Sixty-nine percent in the CKD group
      and 68% in the ESRF group believed that PGD should be offered to other patients.
      DISCUSSION: There was a spectrum of attitudes among this cohort. A proportion of
      patients believe that PGD should be made available to prospective parents with
      this disease. The discrepancy between the low proportion (17% CKD, 18% ESRF) who
      would consider prenatal diagnosis and termination of pregnancy and the higher
      number who hypothetically express an intention or wish to access PGD (50% CKD and
      63% ESRF) indicates far greater acceptability for diagnostic methods that occur
      before embryo implantation. It is not known how the development of methods to
      identify patients whose renal function is likely to decline rapidly and
      treatments altering the natural history of ADPKD will affect these attitudes.

PMID- 27689417
TI  - Immunovirological Efficacy of Once-Daily Maraviroc Plus Ritonavir-Boosted
      Atazanavir After 48 Weeks in Naive HIV-Infected Patients.
AB  - Toxicities related to the use of nucleoside analogues have increased the interest
      in developing nucleoside-sparing regimens, mainly combining protease inhibitors
      with raltegravir. However, data regarding the use of CCR5-antagonists in this
      setting and in the naive scenario are scarce. The main objective was to analyze
      the immunovirological efficacy and tolerability of a low-dose, once-daily,
      maraviroc (MVC)-containing, nucleoside reverse transcriptase inhibitor-sparing
      dual therapy compared with standard triple therapy after 48 weeks for naive HIV
      infected patients in the routine clinical practice setting. All naive HIV
      infected patients with stable clinical condition that started antiretroviral
      treatment since February 1, 2008 to May 30,h 2012 were included. MVC clinical
      test was used to select candidate subjects to MVC therapy. Thirty-two subjects
      with MVC + atazanavir/ritonavir (ATV/r) and 66 with standard triple therapy were
      analyzed. A comparable virological efficacy between groups was found after 48
      weeks (87.5% vs. 80.3% of HIV undetectability, p = 0.37, MVC + ATV/r and triple
      therapy groups, respectively). The CD4 recovery after 48 weeks was similar and
      more than 200 cells/mm3 in both groups. No need of therapy changes or treatment
      discontinuations was observed in the MVC + ATV/r group. Effect on lipid profile,
      high-sensitivity C reactive protein, and beta2-microglobulin was similar for both
      groups. Noteworthy, a significant increase of erythrocyte mean corpuscular volume
      was observed only in the triple therapy group. A nucleoside-sparing MVC
      containing dual therapy showed similar immunovirological efficacy and
      tolerability than standard triple therapy in naive HIV-infected patients.

PMID- 27689418
TI  - Differences in the chemical composition of Enterococcus faecalis biofilm under
      conditions of starvation and alkalinity.
AB  - ABSTACT This study aimed to investigate the dynamic changes that occur in the
      chemical composition of an Enterococcus faecalis (E. faecalis) biofilm under
      conditions of starvation and in an alkaline environment and to explore the
      function of chemical composition changes in the resistance of the E. faecalis
      biofilm to an extreme environment. This study established an in vitro E. faecalis
      biofilm model under starvation and in an alkaline environment. During the
      formation of the biofilm, the pH value and nutritional condition of the culture
      medium were changed, and the changes in chemical composition were observed using
      biochemical measures. The results showed that, when the pH value of the culture
      medium was 11, the percentage of water-insoluble polysaccharides in the biofilm
      was significantly lower than under other conditions. In addition, the percentage
      of water-soluble polysaccharides in culture medium with pH values of 9 and 11
      gradually decreased. The level of the water-soluble polysaccharides in each
      milligram of dry weight of biofilm at pH 11 increased compared to that under
      other conditions. The results from this study indicate that the chemical
      composition of E. faecalis biofilm changed in extreme environments. These changes
      served as a defensive mechanism for E. faecalis against environmental pressures.

PMID- 27689419
TI  - Control of disinfection by-products in canned vegetables caused by water used in
      their processing.
AB  - Canned vegetables come into contact with sanitizers and/or treated water in
      industry during several steps (namely washing, sanitising, blanching and filling
      with sauces or brine solutions) and therefore they can contain disinfection by
      products - DBPs). This study focused on the occurrence of trihalomethanes (THMs)
      and haloacetic acids (HAAs) in a wide variety of canned vegetables (75 samples).
      For each vegetable, the edible solid and liquid phases of the package were
      separated and analysed individually. DBPs can be present in both solid (up to
      eight species) and liquid (up to 11 species) phases, their levels being higher in
      liquid ones. Volatile THMs predominate in the edible solid phase (up to four
      species), while HAAs do so in the liquid phase (up to five species) according to
      their ionic and non-volatile nature. The lowest concentrations of DBPs were found
      in tomatoes because they were often preserved in their own juice, without water.

PMID- 27689420
TI  - A novel minimally invasive, dorsolateral, tubular partial odontoidectomy and
      autologous bone augmentation to treat dens pseudarthrosis: cadaveric, 3D virtual
      simulation study and technical report.
AB  - OBJECTIVE The goal of this study was to demonstrate the clinical and technical
      nuances of a minimally invasive, dorsolateral, tubular approach for partial
      odontoidectomy, autologous bone augmentation, and temporary C1-2 fixation to
      treat dens pseudarthrosis. METHODS A cadaveric feasibility study, a 3D virtual
      reality reconstruction study, and the subsequent application of this approach in
      2 clinical cases are reported. Eight procedures were completed in 4 human
      cadavers. A minimally invasive, dorsolateral, tubular approach for odontoidectomy
      was performed with the aid of a tubular retraction system, using a posterolateral
      incision and an oblique approach angle. Fluoroscopy and postprocedural CT, using
      3D volumetric averaging software, were used to evaluate the degree of bone
      removal of C1-2 lateral masses and the C-2 pars interarticularis. Two clinical
      cases were treated using the approach: a 23-year-old patient with an odontoid
      fracture and pseudarthrosis, and a 35-year-old patient with a history of failed
      conservative treatment for odontoid fracture. RESULTS At 8 cadaveric levels, the
      mean volumetric bone removal of the C1-2 lateral masses on 1 side was 3% +/- 1%,
      and the mean resection of the pars interarticularis on 1 side was 2% +/- 1%. The
      median angulation of the trajectory was 50 degrees , and the median distance from
      the midline of the incision entry point on the skin surface was 67 mm. The
      authors measured the diameter of the working channel in relation to head
      positioning and assessed a greater working corridor of 12 +/- 4 mm in 20 degrees 
      inclination, 15 degrees  contralateral rotation, and 5 degrees  lateral flexion
      to the contralateral side. There were no violations of the dura. The reliability
      of C-2 pedicle screws and C-1 lateral mass screws was 94% (15 of 16 screws) with
      a single lateral breach. The patients treated experienced excellent clinical
      outcomes. CONCLUSIONS A minimally invasive, dorsolateral, tubular odontoidectomy
      and autologous bone augmentation combined with C1-2 instrumentation has the
      ability to provide excellent 1-stage management of an odontoid pseudarthrosis.
      The procedure can be completed safely and successfully with minimal blood loss
      and little associated morbidity. This approach has the potential to provide not
      only a less invasive approach but also a function-preserving option to treat
      complex C1-2 anterior disease.

PMID- 27689421
TI  - Diffusion tensor imaging as a biomarker for assessing neuronal stem cell
      treatments affecting areas distal to the site of spinal cord injury.
AB  - OBJECTIVE The aims of this study were to determine if the morphological and
      functional changes induced by neural stem cell (NSC) grafts after transplantation
      into the rodent spinal cord can be detected using MR diffusion tensor imaging
      (DTI) and, furthermore, if the DTI-derived mean diffusivity (MD) metric could be
      a biomarker for cell transplantation in spinal cord injury (SCI). METHODS A
      spinal contusion was produced at the T-8 vertebral level in 40 Sprague Dawley
      rats that were separated into 4 groups, including a sham group (injury without
      NSC injection), NSC control group (injury with saline injection), co-injection
      control group (injury with Prograf), and the experimental group (injury with NSC
      and Prograf injection). The NSC injection was completed 1 week after injury into
      the site of injury and the rats in the experimental group were compared to the
      rats from the sham, NSC control, and co-injection groups. The DTI index, MD, was
      assessed in vivo at 2, 5, and 10 weeks and ex vivo at 10 weeks postinjury on a
      9.4-T Bruker scanner using a spin-echo imaging sequence. DTI data of the cervical
      spinal cord from the sham surgery, injury with saline injection, injury with
      injection of Prograf only, and injury with C17.2 NSC and Prograf injection were
      examined to evaluate if cellular proliferation induced by intrathoracic C17.2
      engraftment was detectable in a noninvasive manner. RESULTS At 5 weeks after
      injury, the average fractional anisotropy, longitudinal diffusion (LD) and radial
      diffusion (RD) coefficients, and MD of water (average of the RD and LD
      eigenvalues in the stem cell line-treated group) increased to an average of 1.44
      * 10-3 sec/mm2 in the cervical segments, while the control groups averaged 0.98 *
      10-3 s/mm2. Post hoc Tukey's honest significant difference tests demonstrated
      that the transplanted stem cells had significantly higher MD values than the
      other groups (p = 0.032 at 5 weeks). In vivo and ex vivo findings at 10 weeks
      displayed similar results. This statistical difference between the stem cell line
      and the other groups was maintained at the 10-week postinjury in vivo and ex vivo
      time points. CONCLUSIONS These results indicate that the DTI-derived MD metric
      collected from noninvasive imaging techniques may provide useful biomarker
      indices for transplantation interventions that produce changes in the spinal cord
      structure and function. Though promising, the results demonstrated here suggest
      additional work is needed before implementation in a clinical setting.

PMID- 27689422
TI  - Intraoperative electrophysiological monitoring for C1-2 spinal cord stimulation.
AB  - OBJECTIVE This study is a retrospective case series involving C1-2 spinal cord
      stimulation in patients with complex regional pain syndrome (CRPS) under general
      endotracheal anesthesia. Currently, C1-2 paddle lead placement is an accepted
      practice, which provides effective cervical stimulation to ameliorate upper
      extremity and sometimes lower-extremity symptoms experienced by patients with
      CRPS. However, this technique must be performed under general endotracheal
      anesthesia rather than in an awake or semiconscious state due to intraoperative
      safety concerns and patient comfort. The authors aim to provide additional data
      to support the following novel technique: the use of somatosensory evoked
      potential (SSEP) diminution data to assist with proper midline placement of C1-2
      leads under general anesthesia. METHODS SSEP median nerve (MN) and posterior
      tibial nerve (PTN) data were collected from 6 patients undergoing placement of C1
      2 leads under general anesthesia. Fluoroscopy was used as an initial guide for
      proper anatomical midline placement. This was followed by the activation of the
      spinal cord stimulator and simultaneous collection of primarily MN SSEPs as well
      as PTN SSEPs for physiological midline placement. Unilateral and bilateral
      reductions in SSEPs assisted with the correct lateralization of the lead to
      ensure effective postoperative coverage according to the patient's individual
      preoperative symptoms. RESULTS Six patients were monitored using SSEPs and
      repeatable, reliable MN and PTN baseline responses were obtained from all. A
      reduction in amplitude ranging from 5% to 87% was observed, confirming inhibition
      of dorsal column conduction, and an average pain relief of 63% at short-term and
      64% at long-term follow-up was recorded with 6 of 6 and 5 of 6 patients
      responding, respectively. CONCLUSIONS Intraoperative SSEP collision study testing
      appears to be a safe technique to monitor placement of C1-2 paddle leads
      intraoperatively under general anesthesia.

PMID- 27689423
TI  - Letter to the Editor: Electrical activity in limb muscles after spinal cord
      stimulation is not specific for the corticospinal tract.

PMID- 27689424
TI  - Preoperative mental health status may not be predictive of improvements in
      patient-reported outcomes following an anterior cervical discectomy and fusion.
AB  - OBJECTIVE Prior studies have correlated preoperative depression and poor mental
      health status with inferior patient-reported outcomes following lumbar spinal
      procedures. However, literature regarding the effect of mental health on outcomes
      following cervical spinal surgery is limited. As such, the purpose of this study
      is to test for the association of preoperative SF-12 Mental Component Summary
      (MCS) scores with improvements in Neck Disability Index (NDI), SF-12 Physical
      Component Summary (PCS), and neck and arm pain following anterior cervical
      discectomy and fusion (ACDF). METHODS A prospectively maintained surgical
      database of patients who underwent a primary 1- or 2-level ACDF during 2014-2015
      was reviewed. Patients were excluded if they did not have complete patient
      reported outcome data for the preoperative or 6-week, 12-week, or 6-month
      postoperative visits. At baseline, preoperative SF-12 MCS score was assessed for
      association with preoperative NDI, neck visual analog scale (VAS) score, arm VAS
      score, and SF-12 PCS score. The preoperative MCS score was then tested for
      association with changes in NDI, neck VAS, arm VAS, and SF-12 PCS scores from the
      preoperative visit to postoperative visits. These tests were conducted using
      multivariate regression controlling for baseline characteristics as well as for
      the preoperative score for the patient-reported outcome being assessed. RESULTS A
      total of 52 patients were included in the analysis. At baseline, a higher
      preoperative MCS score was negatively associated with a lower preoperative NDI
      (coefficient: -0.74, p < 0.001) and preoperative arm VAS score (-0.06, p =
      0.026), but not preoperative neck VAS score (-0.03, p = 0.325) or SF-12 PCS score
      (0.04, p = 0.664). Additionally, there was no association between preoperative
      MCS score and improvement in NDI, neck VAS, arm VAS, or SF-12 PCS score at any of
      the postoperative time points (6 weeks, 12 weeks, and 6 months, p > 0.05 for
      each). The percentage of patients achieving a minimum clinically important
      difference at 6 months did not differ between the bottom and top MCS score halves
      (p > 0.05 for each). CONCLUSIONS The results of this study suggest that better
      preoperative mental health status is associated with lower perceived preoperative
      disability but is not associated with severity of preoperative neck or arm pain.
      In contrast to other studies, the present study was unable to demonstrate that
      preoperative mental health is predictive of improvement in patient-reported
      outcomes at any postoperative time point following an ACDF.

PMID- 27689425
TI  - Prediction based on preoperative opioid use of clinical outcomes after
      transforaminal lumbar interbody fusions.
AB  - OBJECTIVE Opioid analgesics have become some of the most prescribed drugs in the
      world, despite the lack of long-term studies evaluating the benefits of opioid
      medications versus their risks associated with chronic use. In addition, long
      term opioid use may be associated with worse long-term clinical outcomes. The
      primary objective of this study was to evaluate whether preoperative opioid use
      predicted inferior clinical outcomes among patients undergoing transforaminal
      lumbar interbody fusion (TLIF) for symptomatic lumbar degenerative disc disease.
      METHODS The authors of this observational study prospectively enrolled 93
      patients who underwent 1-level to 2-level TLIFs in 2011-2014; the patient cohort
      was divided into 2 groups according to preoperative opioid use or no such use.
      Visual analog scale (VAS) scores for low-back pain and leg pain, Oswestry
      Disability Index scores, and the scores of the mental component summary (MCS) and
      physical component summary (PCS) on the 36-Item Short Form Health Survey were
      used to assess pain, disability, and health-related quality of life outcomes,
      respectively. The clinical scores for the 2 groups were determined preoperatively
      and at a 12-month follow-up examination. RESULTS In total, 60 (64.5%) patients
      took prescribed opioid medications preoperatively. Compared with those not taking
      opioids preoperatively, these patients had significantly higher VAS scores for
      low-back pain (p = 0.016), greater disability (p = 0.013), and lower PCS scores
      (p = 0.03) at the 12-month follow-up. The postoperative MCS scores were also
      significantly lower (p = 0.035) in the opioid-use group, but these lower scores
      were due to significantly lower baseline MCS scores in this group. A linear
      regression analysis did not detect opioid dose-related effects on leg and back
      pain, disability, and MCS and PCS scores, suggesting that poorer outcomes are not
      significantly correlated with higher opioid doses taken by the patients.
      CONCLUSIONS The use of opioid medications to control pain before patients
      underwent lumbar fusion for degenerative lumbar conditions was associated with
      less favorable clinical outcomes postoperatively. This is the first study that
      has demonstrated this association in a homogeneous cohort of patients undergoing
      TLIF; this association should be studied further to evaluate the conclusions of
      the present study. Clinical trial registration no.: NCT01406405 (
      clinicaltrials.gov ).

PMID- 27689428
TI  - Safety of intensivist-led bedside decannulation of internal jugular bi-caval dual
      lumen veno-venous extracorporeal membrane oxygenation cannulas and report of
      technique.
AB  - BACKGROUND: In the past decade, the rate and utilization of veno-venous
      extracorporeal membrane oxygenation (VV-ECMO) has increased dramatically. A
      single catheter technique has recently come into favour for providing VV-ECMO.
      Although it has been shown that intensivists can safely place these catheters,
      the safety of decannulation by intensivists has not been reported in the
      literature. OBJECTIVE: We describe a technique for safely decannulating the
      Avalon Elite VV-ECMO catheter at the bedside and assess the safety of this
      technique, as compared with the standard technique of decannulation in the
      operating room by a surgeon. METHODS: This was a retrospective cohort design
      conducted at a tertiary care cardiovascular intensive care unit at an academic
      medical centre. All patients who underwent VV-ECMO from 2009 to 2014 were
      included in the study except for those who had been decannulated for withdrawal
      of care. Complication rates from decannulation were compared between patients who
      were decannulated by surgeons in the operating room and those decannulated by
      intensivists in the intensive care unit (ICU). RESULTS: Twenty-eight patients
      were included in this study, of whom twenty-three patients (82%) were
      decannulated by intensivists, board certified in Critical Care Medicine through
      the American Board of Anesthesiology, while five (18%) the patients were
      decannulated by a surgeon. There was no significant difference in the
      complications rates between the surgeons (0) and intensivists (1) (P = 1.00).
      There were no major complications requiring operative intervention associated
      with decannulation identified in this study. CONCLUSIONS: It is safe for
      intensivists to decannulate the Avalon Elite VV-ECMO cannula in the ICU using our
      purse-string suture technique. Performing these decannulations at the bedside
      compared to operating room may have positive clinical ramifications that include
      improved patient safety, timely patient care and reduced operating room costs.

PMID- 27689427
TI  - Development and Validation of the EXPECT Questionnaire: Assessing Patient
      Expectations of Outcomes of Complementary and Alternative Medicine Treatments for
      Chronic Pain.
AB  - BACKGROUND: Patient expectations may be associated with outcomes of complementary
      and alternative medicine (CAM) treatments for chronic pain. However, a
      psychometrically sound measure of such expectations is needed. OBJECTIVES: The
      purpose of this study was to develop and evaluate a questionnaire to assess
      individuals' expectations regarding outcomes of CAM treatments for chronic low
      back pain (CLBP), as well as a short form of the questionnaire. METHODS: An 18
      item draft questionnaire was developed through literature review, cognitive
      interviews with individuals with CLBP, CAM practitioners, and expert
      consultation. Two samples completed the questionnaire: (1) a community sample (n
      = 141) completed it via an online survey before or soon after starting a CAM
      treatment for CLBP, and (2) participants (n = 181) in randomized clinical trials
      evaluating CAM treatments for CLBP or fibromyalgia completed it prior to or
      shortly after starting treatment. Factor structure, internal consistency, test
      retest reliability, and criterion validity were examined. RESULTS: Based on
      factor analyses, 10 items reflecting expectations (used to create a total score)
      and three items reflecting hopes (not scored) were selected for the
      questionnaire. The questionnaire had high internal consistency, moderate test
      retest reliability, and moderate correlations with other measures of
      expectations. A three-item short form also had adequate reliability and validity.
      CONCLUSIONS: The Expectations for Complementary and Alternative Medicine
      Treatments (EXPECT) questionnaire can be used in research to assess individuals'
      expectations of treatments for chronic pain. It is recommended that the three
      hope questions are included (but not scored) to help respondents distinguish
      between hopes and expectations. The short form may be appropriate for clinical
      settings and when expectation measurement is not a primary focus.

PMID- 27689426
TI  - Hysteresis in voltage-gated channels.
AB  - Ion channels constitute a superfamily of membrane proteins found in all living
      creatures. Their activity allows fast translocation of ions across the plasma
      membrane down the ion's transmembrane electrochemical gradient, resulting in a
      difference in electrical potential across the plasma membrane, known as the
      membrane potential. A group within this superfamily, namely voltage-gated
      channels, displays activity that is sensitive to the membrane potential. The
      activity of voltage-gated channels is controlled by the membrane potential, while
      the membrane potential is changed by these channels' activity. This interplay
      produces variations in the membrane potential that have evolved into electrical
      signals in many organisms. These signals are essential for numerous biological
      processes, including neuronal activity, insulin release, muscle contraction,
      fertilization and many others. In recent years, the activity of the voltage-gated
      channels has been observed not to follow a simple relationship with the membrane
      potential. Instead, it has been shown that the activity of voltage-gated channel
      displays hysteresis. In fact, a growing number of evidence have demonstrated that
      the voltage dependence of channel activity is dynamically modulated by activity
      itself. In spite of the great impact that this property can have on electrical
      signaling, hysteresis in voltage-gated channels is often overlooked. Addressing
      this issue, this review provides examples of voltage-gated ion channels
      displaying hysteretic behavior. Further, this review will discuss how Dynamic
      Voltage Dependence in voltage-gated channels can have a physiological role in
      electrical signaling. Furthermore, this review will elaborate on the current
      thoughts on the mechanism underlying hysteresis in voltage-gated channels.

PMID- 27689429
TI  - Changes in heart rate variability during anaesthesia induction using sevoflurane
      or isoflurane with nitrous oxide.
AB  - BACKGROUND: The purpose of this study was to compare cardiac sympathetic and
      parasympathetic balance using heart rate variability (HRV) during induction of
      anaesthesia between sevoflurane and isoflurane in combination with nitrous oxide.
      METHODS: 40 individuals aged from 30 to 60 years, scheduled for general
      anaesthesia were equally divided into sevoflurane or isoflurane groups. After
      100% oxygen inhalation for a few minutes, anaesthesia was induced with nitrous
      oxide 3 L min-1, oxygen 3 L min-1 and sevoflurane or isoflurane. Sevoflurane or
      isoflurane concentration was increased by 0.5% every 2 to 3 breaths until 5% was
      attained for sevoflurane, or 3% for isoflurane. Vecuronium was administered to
      facilitate tracheal intubation. After intubation, sevoflurane was set to 2% while
      isoflurane was set to 1% with nitrous oxide with oxygen (1:1) for 5 min. RESULTS:
      Both sevoflurane and isoflurane provoked a decrease in blood pressure, total
      power, the low frequency component (LF), and high frequency component (HF) of
      HRV. Although the heart rate increased during isoflurane anaesthesia, it
      decreased under sevoflurane. The power of LF and HF also decreased in both
      groups. LF was higher in the isoflurane group while HF was higher in the
      sevoflurane group. The LF/HF ratio increased transiently in the isoflurane group,
      but decreased in the sevoflurane group. CONCLUSION: Anaesthesia induction with
      isoflurane-nitrous oxide transiently increased cardiac sympathetic activity,
      while sevoflurane-nitrous oxide decreased both cardiac sympathetic and
      parasympathetic activities. The balance of cardiac parasympathetic/sympathetic
      activity was higher in sevoflurane anaesthesia.

PMID- 27689430
TI  - Anaphylaxis and cardiac surgery for hypertrophic obstructive cardiomyopathy: a
      case report and review of anaesthetic management.
AB  - BACKGROUND: The aim of this paper is to describe clinical management in a
      situation where patient has experienced anaphylaxis while undergoing surgical
      septal myectomy for hypertrophic obstructive cardiomyopathy (HOCM). CASE REPORT:
      A 40-yr-old female was scheduled to undergo surgical septal myectomy for the
      treatment of HOCM. After induction, the patient developed refractory hypotension
      that did not respond to escalating doses of vasopressors and volume therapy.
      Although a clinical examination led to the diagnosis of anaphylaxis, epinephrine,
      which is the usual treatment of choice, failed to improve the patient's
      haemodynamics. A transesophageal echocardiography revealed a worsening of left
      ventricular outflow tract obstruction (LVOTO) after epinephrine administration.
      In the end, the rapid institution of a cardiopulmonary bypass was required as a
      rescue therapy instead of to save a patient. CONCLUSION: The anaesthetic goals in
      a patient in HOCM are to maintain preload and afterload and to avoid stimulation
      of inotropy and chronotropy to leading to left ventricular outflow obstruction.
      In a patient with anaphylaxis, maintaining these haemodynamic goals becomes much
      more difficult since the pathophysiology and usual treatment of choice will
      worsen LVOTO. Special consideration for the need to have extracorporeal life
      support to treat refractory hypotension in surgical patients with HOCM may be
      warranted.

PMID- 27689431
TI  - Selected aspects of epidemiological surveillance in the intensive care unit of
      the Centre of Pulmonology and Thoracic Surgery in Bystra.

PMID- 27689432
TI  - Enantioselective Cu-Catalyzed Arylation of Secondary Phosphine Oxides with
      Diaryliodonium Salts toward the Synthesis of P-Chiral Phosphines.
AB  - Catalytic synthesis of nonracemic P-chiral phosphine derivatives remains a
      significant challenge. Here we report Cu-catalyzed enantioselective arylation of
      secondary phosphine oxides with diaryliodonium salts for the synthesis of
      tertiary phosphine oxides with high enantiomeric excess. The new process is
      demonstrated on a wide range of substrates and leads to products that are well
      established P-chiral catalysts and ligands.

PMID- 27689433
TI  - Piperitone Profiling in Fine Red Bordeaux Wines: Geographical Influences in the
      Bordeaux Region and Enantiomeric Distribution.
AB  - Piperitone was recently identified in red Bordeaux wines, and this study was
      designed to further explore its contribution to wine aroma. Firstly, a
      geographical origin effect was detected within the Bordeaux region (left versus
      right banks of the Gironde estuary), with significantly higher mint aroma
      intensities and piperitone levels in wines from the left bank (Medoc
      appellations). Statistical analysis of chemical and sensory data highlighted a
      correlation with the proportion of Cabernet Sauvignon in the wine blends.
      Accordingly, it was suggested that these sensory and chemical differences may be
      of varietal origin. Secondly, the contribution of piperitone to minty aromas in
      the aging bouquet was confirmed by combining both sensory and chemical data from
      a wide range of red Bordeaux wines. Subsequent investigation of the enantiomeric
      distribution of piperitone found a significantly higher proportion of the (+)
      (6S) enantiomeric form in wines displaying a strong aging bouquet.

PMID- 27689434
TI  - Cabergoline or bromocriptine for prolactinoma?
AB  - Cabergoline and bromocriptine are among the most commonly used drugs to treat
      prolactinoma. Cabergoline is a long-acting dopamine receptor agonist which might
      offer advantages over bromocriptine. However, it is not clear if this translates
      into clinical benefits. Searching in Epistemonikos database, which is maintained
      by screening 30 databases, we identified two systematic reviews including 12
      studies addressing the question of this article, including five randomized
      controlled trials. We combined the evidence using meta-analysis and generated a
      summary of findings following the GRADE approach. We concluded cabergoline is
      more effective than bromocriptine in resolution of amenorrhea/oligomenorrhea and
      galactorrhea, it probably increases pregnancy rate, and it is associated to less
      adverse effects. It is not clear whether cabergoline is also more effective with
      respect to tumor growth because the certainty of the evidence is very low.

PMID- 27689435
TI  - Specific premature epigenetic aging of cartilage in osteoarthritis.
AB  - Osteoarthritis (OA) is a disease affecting multiple tissues of the joints in the
      elderly, but most notably articular cartilage. Premature biological aging has
      been described in this tissue and in blood cells, suggesting a systemic component
      of premature aging in the pathogenesis of OA. Here, we have explored epigenetic
      aging in OA at the local (cartilage and bone) and systemic (blood) levels. Two
      DNA methylation age-measures (DmAM) were used: the multi-tissue age estimator for
      cartilage and bone; and a blood-specific biomarker for blood. Differences in DmAM
      between OA patients and controls showed an accelerated aging of 3.7 years in
      articular cartilage (95% CI = 1.1 to 6.3, P = 0.008) of OA patients. By contrast,
      no difference in epigenetic aging was observed in bone (0.04 years; 95% CI = -1.8
      to 1.9, P = 0.3) and in blood (-0.6 years; 95% CI = -1.5 to 0.3, P = 0.2) between
      OA patients and controls. Therefore, premature epigenetic aging according to DNA
      methylation changes was specific of OA cartilage, adding further evidence and
      insight on premature aging of cartilage as a component of OA pathogenesis that
      reflects damage and vulnerability.

PMID- 27689436
TI  - Quantification of Small Extracellular Vesicles by Size Exclusion Chromatography
      with Fluorescence Detection.
AB  - Chemical analysis of small extracellular vesicles (sEVs) circulating in body
      fluids holds potentials in noninvasive diagnosis of diseases and evaluation of
      therapeutic treatments. However, quantification of sEVs remains a challenge due
      to lacking of cost-effective analytical protocols. Herein we report a facile
      method based on size exclusion chromatography with fluorescence detection (SEC
      FD) for sEVs quantification. After removal of cells and cell debris, a 0.50 mL
      sample (e.g., cell culture medium) is incubated with CM-Dil dye to fluorescently
      label sEVs. The incubation solution is then separated on a SEC column packed with
      Sepharose CL-4B. The eluent is monitored fluorescently at Ex553 nm/Em570 nm by
      using a fluorometer equipped with a 50-MUL flow through cuvette. Separation
      efficiency of the proposed SEC-FD method was evaluated by analyzing 100 nm
      liposomes and albumin-FITC conjugate. Liposomes were eluted out in less than 6
      min, about 10 min before albumin-FITC. A separation repeatability (RSD in
      retention time) of 1.4% (n = 5) was obtained for liposomes. In analysis of cell
      culture media, linear calibration curves based on SEC-FD peak height versus sEVs
      concentration were obtained with r2 value of 0.996. Intraday quantification
      repeatability (RSD in peak height) was 3.2% (n = 5). The detection limit was
      estimated to be 2.9 * 107 exosome particles/mL. The proposed assay was applied to
      the first study of sEVs secretion from TK6 cells cultured in serum-free medium
      for a culturing period from 1 to 48 h.

PMID- 27689437
TI  - Levels, Isomer Profiles, and Estimated Riverine Mass Discharges of Perfluoroalkyl
      Acids and Fluorinated Alternatives at the Mouths of Chinese Rivers.
AB  - An extensive sampling campaign was undertaken to study the levels, isomer
      profiles and riverine mass discharges of perfluoroalkyl acids (PFAAs) and
      fluorinated alternatives in 19 Chinese rivers. The levels and homologue profiles
      of Sigma10PFAAs varied considerably among the 19 rivers (mean 106; median 16.3,
      range 8.9-1240 ng/L), indicating the influence of specific point sources. Highly
      branched isomer profiles of perfluorooctanoic acid (18-25% br-PFOA) in rivers
      with elevated concentrations (96-352 ng/L) indicate that releases during
      production of PFOA by electrochemical fluorination and/or its use in
      fluoropolymer manufacture were the dominant sources to these rivers. The
      fluorinated alternatives 6:2 fluorotelomer sulfonate (detection frequency 21%, <
      0.1-3.1 ng/L) and chlorinated polyfluoroalkyl ether sulfonate F-53B (51%, < 0.56
      78.5 ng/L) were also found in some rivers. The total Chinese riverine mass
      discharges of PFOA (mean 80.9; range 16.8-168 t/y) (including monitoring data
      from this and other studies) were in good agreement with theoretical PFOA
      emission estimates (17.3-203 t/y) whereas riverine mass discharges of PFOS (mean
      3.6; range 1.9-5.6 t/y) could only account for a minor fraction of theoretically
      estimated PFOS releases (70 t/y). This study provides empirical evidence that
      emissions from Chinese point sources likely dominate the global emissions of
      several legacy PFASs (notably PFOA) and fluorinated alternatives (e.g., F-53B).

PMID- 27689438
TI  - Computational Exploration of the Li-Electrode|Electrolyte Interface in the
      Presence of a Nanometer Thick Solid-Electrolyte Interphase Layer.
AB  - A nanometer thick passivation layer will spontaneously form on Li-metal in
      battery applications due to electrolyte reduction reactions. This passivation
      layer in rechargeable batteries must have "selective" transport properties:
      blocking electrons from attacking the electrolytes, while allowing Li+ ion to
      pass through so the electrochemical reactions can continue. The classical
      description of the electrochemical reaction, Li+ + e -> Li0, occurring at the Li
      metal|electrolyte interface is now complicated by the passivation layer and will
      reply on the coupling of electronic and ionic degrees of freedom in the layer.
      This passivation layer is called "solid electrolyte interphase (SEI)" and is
      considered as "the most important but the least understood in rechargeable Li-ion
      batteries," partly due to the lack of understanding of its structure-property
      relationship. Predictive modeling, starting from the ab initio level, becomes an
      important tool to understand the nanoscale processes and materials properties
      governing the interfacial charge transfer reaction at the Li
      metal|SEI|electrolyte interface. Here, we demonstrate pristine Li-metal surfaces
      indeed dissolve in organic carbonate electrolytes without the SEI layer. Based on
      joint modeling and experimental results, we point out that the well-known two
      layer structure of SEI also exhibits two different Li+ ion transport mechanisms.
      The SEI has a porous (organic) outer layer permeable to both Li+ and anions
      (dissolved in electrolyte), and a dense (inorganic) inner layer facilitate only
      Li+ transport. This two-layer/two-mechanism diffusion model suggests only the
      dense inorganic layer is effective at protecting Li-metal in electrolytes. This
      model suggests a strategy to deconvolute the structure-property relationships of
      the SEI by analyzing an idealized SEI composed of major components, such as
      Li2CO3, LiF, Li2O, and their mixtures. After sorting out the Li+ ion diffusion
      carriers and their diffusion pathways, we design methods to accelerate the Li+
      ion conductivity by doping and by using heterogonous structure designs. We will
      predict the electron tunneling barriers and connect them with measurable first
      cycle irreversible capacity loss. Finally, we note that the SEI not only affects
      Li+ and e- transport, but it can also impose a potential drop near the Li
      metal|SEI interface. Our challenge is to fully describe the electrochemical
      reactions at the Li-metal|SEI|electrolyte interface. This will be the subject of
      ongoing efforts.

PMID- 27689439
TI  - Slow Auger Recombination of Charged Excitons in Nonblinking Perovskite
      Nanocrystals without Spectral Diffusion.
AB  - Over the last two decades, intensive research efforts have been devoted to the
      suppressions of photoluminescence (PL) blinking and Auger recombination in metal
      chalcogenide nanocrystals (NCs), with significant progresses being made only very
      recently in few specific NC structures. Here we show that nonblinking PL is
      readily available in the newly synthesized perovskite CsPbI3 NCs and that their
      Auger recombination of charged excitons is greatly slowed down, as signified by a
      PL lifetime about twice shorter than that of neutral excitons. Moreover, spectral
      diffusion is completely absent in single CsPbI3 NCs at the cryogenic temperature,
      leading to a resolution-limited PL line width of ~200 MUeV.

PMID- 27689440
TI  - Multisynergistic Platform for Tumor Therapy by Mild Microwave Irradiation
      Activated Chemotherapy and Enhanced Ablation.
AB  - Microwave (MW) therapy, as a promising type of thermal therapy, has been
      attracting more and more attention from scientists. The combination of thermal
      and chemotherapy is of great significance in the latest studies of synergistic
      tumor therapy. However, the research on the MW therapy mechanism, especially the
      nonthermal effect applied in the combined cancer therapy, is not thorough enough.
      Pleasantly, we have discovered that nonthermal MW irradiation can promote the
      cellular uptake of nanoparticles and anticancer drugs via experiments in vitro
      and in vivo. Therefore, multifunctional nanoplatforms have been designed for
      enhanced tumor inhibition by loading ionic liquids (ILs), doxorubicin
      hydrochloride (DOX), and phase change materials (PCMs) into ZrO2 hollow
      nanoparticles. PCMs act as MW switches. The as-made IL-DOX-PCM@ZrO2 nanoplatforms
      were injected into H22-tumor-bearing mice via the tail vein. Mild microwave
      irradiation (0.9 W, 450 MHz) was then applied. The thermal effect of MW could
      cause the temperature of the tumor site to rise (58  degrees C). On the other
      hand, it will trigger the MW switch to open and release DOX when the temperature
      is high enough. At the same time as drug release, a MW nonthermal effect could
      improve the cellular uptake of nanomaterials and anticancer drugs. The
      multisynergistic effect can promote the survival rate of the IL-DOX-PCM@ZrO2+MW
      group to 100%. The results of the tumor therapy experiment in vivo demonstrated
      that as-made multifunctional IL-DOX-PCM@ZrO2 nanoplatforms could enhance the
      therapeutic outcome of combined thermal and chemotherapy under mild MW
      irradiation.

PMID- 27689441
TI  - Enhanced Radiosensitization of Gold Nanospikes via Hyperthermia in Combined
      Cancer Radiation and Photothermal Therapy.
AB  - Metallic nanostructures as excellent candidates for nanosensitizers have shown
      enormous potentials in cancer radiotherapy and photothermal therapy. Clinically,
      a relatively low and safe radiation dose is highly desired to avoid damage to
      normal tissues. Therefore, the synergistic effect of the low-dosed X-ray
      radiation and other therapeutic approaches (or so-called "combined therapeutic
      strategy") is needed. Herein, we have synthesized hollow and spike-like gold
      nanostructures by a facile galvanic replacement reaction. Such gold nanospikes
      (GNSs) with low cytotoxicity exhibited high photothermal conversion efficiency
      (eta = 50.3%) and had excellent photostability under cyclic near-infrared (NIR)
      laser irradiations. We have demonstrated that these GNSs can be successfully used
      for in vitro and in vivo X-ray radiation therapy and NIR photothermal therapy.
      For the in vitro study, colony formation assay clearly demonstrated that GNS
      mediated photothermal therapy and X-ray radiotherapy reduced the cell survival
      fraction to 89% and 51%, respectively. In contrast, the cell survival fraction of
      the combined radio- and photothermal treatment decreased to 33%. The synergistic
      cancer treatment performance was attributable to the effect of hyperthermia,
      which efficiently enhanced the radiosensitizing effect of hypoxic cancer cells
      that were resistant to ionizing radiation. The sensitization enhancement ratio
      (SER) of GNSs alone was calculated to be about 1.38, which increased to 1.63 when
      the GNS treatment was combined with the NIR irradiation, confirming that GNSs are
      effective radiation sensitizers to enhance X-ray radiation effect through
      hyperpyrexia. In vivo tumor growth study indicated that the tumor growth
      inhibition (TGI) in the synergistically treated group reached 92.2%, which was
      much higher than that of the group treated with the GNS-enhanced X-ray radiation
      (TGI = 29.8%) or the group treated with the GNS-mediated photothermal therapy
      (TGI = 70.5%). This research provides a new method to employ GNSs as
      multifunctional nanosensitizers for synergistic NIR photothermal and X-ray
      radiation therapy in vitro and in vivo.

PMID- 27689443
TI  - Master Equation Analysis of Thermal and Nonthermal Microwave Effects.
AB  - Master equation is a successful model to describe the conventional heating
      reaction, it is expanded to capture the "microwave effect" in this work. The work
      equation of "microwave effect" included master equation presents the direct
      heating, indirect heating, and nonthermal effect about the microwave field. The
      modified master equation provides a clear physics picture to the nonthermal
      microwave effect: (1) The absorption and the emission of the microwave, which is
      dominated by the transition dipole moment between two corresponding states and
      the intensity of the microwave field, provides a new path to change the reaction
      rate constants. (2) In the strong microwave field, the distribution of internal
      states of the molecules will deviate from the equilibrium distribution, and the
      system temperature defined in the conventional heating reaction is no longer
      available. According to the general form of "microwave effect" included master
      equation, a two states model for unimolecular dissociation is proposed and is
      used to discuss the microwave nonthermal effect particularly. The average rate
      constants can be increased up to 2400 times for some given cases without the
      temperature changed in the two states model. Additionally, the simulation of a
      model system was executed using our State Specified Master Equation package.
      Three important conclusions can be obtained in present work: (1) A reasonable
      definition of the nonthermal microwave effect is given in the work equation of
      "microwave effect" included master equation. (2) Nonthermal microwave effect
      possibly exists theoretically. (3) The reaction rate constants perhaps can be
      changed obviously by the microwave field for the non-RRKM and the mode-specified
      reactions.

PMID- 27689442
TI  - Fabrication and Unique Optical Properties of Two-Dimensional Silver Nanorod
      Arrays with Nanometer Gaps on a Silicon Substrate from a Self-Assembled Template
      of Diblock Copolymer.
AB  - A periodic array of nanoholes was fabricated via the self-assembly of a
      polystyrene(PS)-b-poly(methyl methacrylate) (PMMA) block copolymer (BCP) on a
      silicon substrate and selective etching of the PMMA moieties. Silver nanorods
      (AgNRs) were then selectively deposited in the nanoholes by a galvanic
      displacement reaction where the pattern was hexagonally aligned according to the
      template. The diameter of AgNRs was controlled by changing the immersion time.
      Optical measurements of the AgNR arrays revealed that the extinction peak was
      split into two because of the electromagnetically induced transparency effect. In
      addition, the AgNR arrays showed a surface-enhanced Raman scattering response and
      were successfully transferred from a silicon substrate to a transparent and
      flexible polymer film while retaining the rod arrangement.

PMID- 27689444
TI  - Phosphatidylserine Allows Observation of the Calcium-Myristoyl Switch of
      Recoverin and Its Preferential Binding.
AB  - Recoverin undergoes a calcium-myristoyl switch during visual phototransduction.
      Indeed, calcium binding by recoverin results in the extrusion of its myristoyl
      group, which allows its membrane binding. However, the contribution of particular
      lipids and of specific amino acids of recoverin in its membrane binding has not
      yet been demonstrated. In the present work, the affinity of recoverin for the
      negatively charged phosphatidylserine has been clearly shown to be governed by a
      cluster of positively charged residues located in its N-terminal segment.
      Moreover, the calcium-myristoyl switch of recoverin was only observed upon
      binding onto monolayers of phosphatidylserine and not in the case of other
      anionic phospholipids. Fluorescence microscopy experiments with mixed lipid
      monolayers allowed confirmation of the specific binding of myristoylated
      recoverin to phosphatidylserine, whereas the extent of penetration of recoverin
      in phosphatidylserine monolayers was estimated by ellipsometry. A model has thus
      been proposed for the membrane binding of myristoylated recoverin in the presence
      of calcium.

PMID- 27689445
TI  - A Water-Soluble Cationic Zinc Lysine Precursor for Coating ZnO on Biomaterial
      Surfaces.
AB  - A novel water-soluble cationic zinc lysine coordination compound,
      [Zn[(C6H14N2O2)]2Cl]Cl.2H2O (1), has been designed and synthesized and its
      crystal structure determined. The aqueous solution of this coordination compound
      is not only transparent and stable at room temperature but it is also nearly
      neutral (pH ~ 7). It is worth noting that zinc oxide (ZnO) forms in situ upon
      dilution of a solution of the compound. The bioactivity of ZnO has been confirmed
      using an Alarma Blue assay. These unique properties allow the coordination
      compound to gently grow ZnO coating with excellent antibacterial benefits onto
      biomaterial surfaces in a facile and safe manner.

PMID- 27689446
TI  - Red-Emitting Tetracoordinate Organoboron Chelates: Synthesis, Photophysical
      Properties, and Fluorescence Microscopy.
AB  - Seven tetracoordinate organoboron fluorophores with heterobiaryl N,O- or N,N
      chelate ligands were prepared and photophysically characterized (in toluene). The
      electronic variation of the heteroaromatic moiety provided a means for the fine
      tuning of the UV/vis absorption and emission spectra. In the most interesting
      cases, the spectra were red-shifted to maximum absorbance at wavelengths longer
      than 500 nm and emission maxima between 620 and 660 nm. The pronounced
      intramolecular charge-transfer character of the dyes yielded large Stokes shifts
      (3500-5100 cm-1), while maintaining appreciable fluorescence quantum yields of up
      to 0.2 for emission maxima longer than 600 nm. The lipophilic character of the
      dyes enabled their application as stains of vesicle substructures in confocal
      fluorescence microscopy imaging.

PMID- 27689447
TI  - Influence of time dependent longitudinal magnetic fields on the cooling process,
      exchange bias and magnetization reversal mechanism in FM core/AFM shell
      nanoparticles: a Monte Carlo study.
AB  - Using Monte Carlo simulations, we have investigated the dynamic phase transition
      properties of magnetic nanoparticles with ferromagnetic core coated by an
      antiferromagnetic shell structure. Effects of field amplitude and frequency on
      the thermal dependence of magnetizations, magnetization reversal mechanisms
      during hysteresis cycles, as well as on the exchange bias and coercive fields
      have been examined, and the feasibility of applying dynamic magnetic fields on
      the particle have been discussed for technological and biomedical purposes.

PMID- 27689448
TI  - State-of-the-Art Thermochemical and Kinetic Computations for Astrochemical
      Complex Organic Molecules: Formamide Formation in Cold Interstellar Clouds as a
      Case Study.
AB  - We describe an integrated computational strategy aimed at providing reliable
      thermochemical and kinetic information on the formation processes of
      astrochemical complex organic molecules. The approach involves state-of-the-art
      quantum-mechanical computations, second-order vibrational perturbation theory,
      and kinetic models based on capture and transition state theory together with the
      master equation approach. Notably, tunneling, quantum reflection, and leading
      anharmonic contributions are accounted for in our model. Formamide has been
      selected as a case study in view of its interest as a precursor in the abiotic
      amino acid synthesis. After validation of the level of theory chosen for
      describing the potential energy surface, we have investigated several pathways of
      the OH + CH2NH and NH2 + H2CO reaction channels. Our results show that both
      reaction channels are essentially barrierless (in the sense that all relevant
      transition states lie below or only marginally above the reactants) and once
      tunneling is taken into the proper account indicate that the reaction can occur
      under the low temperature conditions of interstellar environments.

PMID- 27689449
TI  - Managing and Mitigating the Health Risks of Climate Change: Calling for Evidence
      Informed Policy and Action.

PMID- 27689450
TI  - Theoretical Foundation for Electric-Dipole-Allowed Chiral-Specific Fluorescence
      Optical Rotary Dispersion (F-ORD) from Interfacial Assemblies.
AB  - Fluorescence optical rotary dispersion (F-ORD) is proposed as a novel chiral
      specific and interface-specific spectroscopic method. F-ORD measurements of
      uniaxial assemblies are predicted to be fully electric-dipole-allowed, with
      corresponding increases in sensitivity to chirality relative to chiral-specific
      measurements in isotropic assemblies that are commonly interpreted through
      coupling between electric and magnetic dynamic dipoles. Observations of strong
      chiral sensitivity in prior single-molecule fluorescence measurements of chiral
      interfacial molecules are in excellent qualitative agreement with the predictions
      of the F-ORD mechanism and challenging to otherwise explain. F-ORD may provide
      methods to suppress background fluorescence in studies of biological interfaces,
      as the detected signal requires both polar local order and interfacial chirality.
      In addition, the molecular-level descriptions of the mechanisms underpinning F
      ORD may also potentially apply to aid in interpreting chiral-specific Raman and
      surface-enhanced Raman spectroscopy measurements of uniaxially oriented
      assemblies, opening up opportunities for chiral-specific and interface-specific
      vibrational spectroscopy.

PMID- 27689452
TI  - Financial Burden Secondary to Delay in Cholecystectomy Following Mild Biliary
      Pancreatitis.
AB  - AIM OF THE STUDY: The guidelines recommend that patients with mild gallstones
      pancreatitis should undergo a definitive management for gallstones during the
      same admission or within the next two weeks. The aim of this study was to
      estimate the financial cost resulting from a delay in surgical management
      following mild gallstones pancreatitis. This includes the costs of readmissions
      with biliary events and the subsequent investigations required during these
      admissions. MATERIALS AND METHODS: A retrospective analysis included patients
      with gallstone pancreatitis who were admitted to a district general hospital in
      the United Kingdom over one year. Patients with severe pancreatitis and those
      unfit for surgery were excluded. RESULTS: Forty patients were included in the
      study, 27 females (67%) and 13 males (33%). Mean age was 50.2 years. Twenty-two
      patients of the total presented with a single admission with gallstone
      pancreatitis prior to an elective surgery; however, 18 patients (45%) required
      recurrent admissions. The duration between the first admission and surgery ranged
      from 14 to 389 days (median of 99 days). Only one patient (2.5%) had
      cholecystectomy within two weeks of admission as per guidelines. Twenty-two
      ultrasound scans, four computed tomography scans, 15 magnetic resonance
      cholangiopancreatography, and two endoscopic retrograde cholangiopancreatography
      were the total of the extra-investigations required during readmissions.
      Estimated costs of extra admissions and extra investigations exceeded L33,000.
      CONCLUSIONS: The delay in cholecystectomy for patients admitted with mild
      gallstone pancreatitis and fit for surgery has resulted in high readmission rate
      with biliary events, and subsequently high extrax costs.

PMID- 27689451
TI  - Delivery of bevacizumab to atheromatous porcine carotid tissue using echogenic
      liposomes.
AB  - Ultrasound is both a valuable diagnostic tool and a promoter of beneficial tissue
      bioeffects for the treatment of cardiovascular disease. Vascular effects can be
      mediated by mechanical oscillations of circulating microbubbles that may also
      encapsulate and shield therapeutic agents in the bloodstream. Here, the effect of
      color-Doppler ultrasound exposure on bevacizumab-loaded liposome delivery into
      the vascular bed was assessed in atheromatous porcine carotids. Bevacizumab, an
      anti-angiogenic antibody to vascular endothelial growth factor (VEGF-A), was
      loaded into echogenic liposomes (BEV-ELIP) and confirmed to be immunoreactive.
      BEV-ELIP flowing within the lumen were exposed to color-Doppler ultrasound at
      three acoustic pressures for 3.5 min during treatment at physiologic temperature
      and fluid pressure. To confirm the presence of bubble activity, cavitation was
      detected within the lumen by a single-element passive cavitation detector. After
      treatment, the artery was fixed at physiologic pressure and subjected to
      immunohistochemical analysis to assess the penetration of bevacizumab within the
      carotid wall. The results suggest that other factors may more strongly influence
      the deposition of bevacizumab into carotid tissue than color-Doppler ultrasound
      and cavitation. In both sets of arteries, preferential accumulation of
      bevacizumab occurred in locations associated with atheroma progression and
      neointimal thickening: fibrous tissue, necrotic plaque and areas near macrophage
      infiltration. The delivery of bevacizumab to carotid vascular tissue correlated
      with the properties of the tissue bed, such as permeability, or affinity for
      growth-factor binding. Future investigations using this novel therapeutic
      strategy may focus on characterizing the spatial extent of delivery and
      bevacizumab colocalization with biochemical markers of atheroma.

PMID- 27689453
TI  - Concomitant Medication Use and New-Onset Diabetes Among Medicaid Beneficiaries
      with Chronic Obstructive Pulmonary Disease.
AB  - Use of multiple prescription medications is common among individuals with chronic
      obstructive pulmonary disease (COPD) because of coexisting inflammatory-related
      conditions. Specifically, the use of antidepressants, inhaled corticosteroids
      (ICSs), and statins may place individuals with COPD at high risk for new-onset
      diabetes. The objective was to examine the relationship between the use of
      antidepressants, ICSs, and statins and new-onset diabetes among Medicaid
      beneficiaries with COPD. This study used a retrospective longitudinal cohort
      design using multiple years (2005-2008) of Medicaid claims for beneficiaries with
      newly diagnosed COPD (n = 15,287), who were diabetes free at baseline. National
      Drug Codes were used to determine the receipt of antidepressants, ICSs, and
      statins, and International Classification of Diseases, Ninth Revision, Clinical
      Modification codes were used to define new-onset diabetes (250.x2). Multivariable
      logistic regression was used to examine the adjusted relationship between
      medication use and new-onset diabetes. Overall, 6.3% of the study population was
      diagnosed with new-onset diabetes. After controlling for baseline
      characteristics, individuals using ICSs (adjusted odds ratio [AOR]: 1.23; 95%
      confidence interval [CI]: 1.07, 1.47) or statins (AOR: 1.48; 95% CI: 1.27, 1.72)
      had a greater risk of new-onset diabetes compared to those not given ICSs,
      statins, or antidepressants. Analyses using combined medication categories
      revealed that adults using statins in combination with both antidepressants and
      ICSs, or when combined with ICS, were more likely to have new-onset diabetes.
      These findings indicate that multiple medication use (ICSs and statins) was
      associated with increased rates of new-onset diabetes. Further research is
      warranted to understand this association.

PMID- 27689454
TI  - PulseRider-assisted treatment of wide-necked intracranial bifurcation aneurysms:
      safety and feasibility study.
AB  - OBJECTIVE The goal of this study was to assess the safety and feasibility of
      PulseRider, a novel endovascular stent, in the treatment of intracranial
      bifurcation aneurysms with wide necks. The authors present the initial results of
      the first 10 cases in which the PulseRider device was used. METHODS Patients
      whose aneurysms were intended to be treated with the PulseRider device at 2
      institutions in the United Kingdom were identified prospectively. Patient
      demographics, procedural details, immediate neurological and clinical status, and
      immediate angiographic outcomes and 6-month clinical and imaging follow-up were
      recorded prospectively. RESULTS At the end of the procedure, all 10 patients
      showed complete aneurysm occlusion (Raymond Class 1). There were no significant
      intraprocedural complications except for an occurrence of thromboembolism without
      clinical sequelae. There was no occurrence of aneurysm rupture or vessel
      dissection. At 6-month follow-up, 7 and 3 patients had modified Rankin Scale
      scores of 0 and 1, respectively. All 10 patients had stable aneurysm occlusion
      (Raymond Class 1) and daughter vessel intraluminal patency on 6-month follow-up
      catheter angiography. CONCLUSIONS The authors' early experience with the
      PulseRider device demonstrates that it is a safe and effective adjunct in the
      treatment of bifurcation aneurysms with wide necks arising at the middle cerebral
      artery bifurcation, anterior cerebral artery, basilar apex, and carotid terminus.
      It works by providing a scaffold at the neck of the bifurcation aneurysm,
      enabling neck remodeling and coil support while maintaining parent vessel
      intraluminal patency. Early clinical and radiological follow-up showed good
      functional outcome and stable occlusion rates, respectively. Further data are
      needed to assess medium- and long-term outcomes with PulseRider.

PMID- 27689455
TI  - Letter to the Editor: Cranioplasty after decompressive craniectomy.

PMID- 27689456
TI  - Editorial. Initial experience with PulseRider treatment for wide-necked
      bifurcation aneurysms.

PMID- 27689457
TI  - Letter to the Editor: Enlargement of the middle meningeal artery.

PMID- 27689458
TI  - The force pyramid: a spatial analysis of force application during virtual reality
      brain tumor resection.
AB  - OBJECTIVE Virtual reality simulators allow development of novel methods to
      analyze neurosurgical performance. The concept of a force pyramid is introduced
      as a Tier 3 metric with the ability to provide visual and spatial analysis of 3D
      force application by any instrument used during simulated tumor resection. This
      study was designed to answer 3 questions: 1) Do study groups have distinct force
      pyramids? 2) Do handedness and ergonomics influence force pyramid structure? 3)
      Are force pyramids dependent on the visual and haptic characteristics of
      simulated tumors? METHODS Using a virtual reality simulator, NeuroVR (formerly
      NeuroTouch), ultrasonic aspirator force application was continually assessed
      during resection of simulated brain tumors by neurosurgeons, residents, and
      medical students. The participants performed simulated resections of 18 simulated
      brain tumors with different visual and haptic characteristics. The raw data,
      namely, coordinates of the instrument tip as well as contact force values, were
      collected by the simulator. To provide a visual and qualitative spatial analysis
      of forces, the authors created a graph, called a force pyramid, representing
      force sum along the z-coordinate for different xy coordinates of the tool tip.
      RESULTS Sixteen neurosurgeons, 15 residents, and 84 medical students participated
      in the study. Neurosurgeon, resident and medical student groups displayed easily
      distinguishable 3D "force pyramid fingerprints." Neurosurgeons had the lowest
      force pyramids, indicating application of the lowest forces, followed by resident
      and medical student groups. Handedness, ergonomics, and visual and haptic tumor
      characteristics resulted in distinct well-defined 3D force pyramid patterns.
      CONCLUSIONS Force pyramid fingerprints provide 3D spatial assessment displays of
      instrument force application during simulated tumor resection. Neurosurgeon force
      utilization and ergonomic data form a basis for understanding and modulating
      resident force application and improving patient safety during tumor resection.

PMID- 27689459
TI  - The effects of new or worsened postoperative neurological deficits on survival of
      patients with glioblastoma.
AB  - OBJECTIVE An increased extent of resection (EOR) has been shown to improve
      overall survival of patients with glioblastoma (GBM) but has the potential for
      causing a new postoperative neurological deficit. To investigate the impact of
      surgical neurological morbidity on survival, the authors performed a
      retrospective analysis of the clinical data from patients with GBM to quantify
      the impact of a new neurological deficit on the survival benefit achieved with an
      increased EOR. METHODS The data from all GBM patients who underwent resection at
      the University of Florida from 2010 to 2015 with postoperative imaging within 72
      hours of surgery were included in the study. Retrospective analysis was performed
      on clinical outcomes and tumor volumes determined on postoperative and follow-up
      imaging examinations. RESULTS Overall, 115 patients met the inclusion criteria
      for the study. Tumor volume at the time of presentation was a median of 59 cm3
      (enhanced on T1-weighted MRI scans). The mean EOR (+/- SD) was 94.2% +/- 8.7%
      (range 59.9%-100%). Almost 30% of patients had a new postoperative neurological
      deficit, including motor weakness, sensory deficits, language difficulty, visual
      deficits, confusion, and ataxia. The neurological deficits had resolved in 41% of
      these patients on subsequent follow-up examinations. The median overall survival
      was 13.1 months (95% CI 10.9-15.2 months). Using a multipredictor Cox model, the
      authors observed that increased EOR was associated with improved survival except
      for patients with smaller tumor volumes (<= 15 cm3). A residual volume of 2.5 cm3
      or less predicted a favorable overall survival. Developing a postoperative
      neurological deficit significantly affected survival (9.2 months compared with
      14.7 months, p = 0.02), even if the neurological deficit had resolved by the
      first follow-up. However, there was a trend of improved survival among patients
      with resolution of a neurological deficit by the first follow-up compared with
      patients with a permanent neurological deficit. Any survival benefit from
      achieving a 95% EOR was abrogated by the development of a new neurological
      deficit postoperatively. CONCLUSIONS Developing a new neurological deficit after
      resection of GBM is associated with a decrease in overall survival. A careful
      balance between EOR and neurological compromise needs to be taken into account to
      reduce the likelihood of neurological morbidity from surgery.

PMID- 27689460
TI  - A rare case of central nervous system amyloidoma treated with fractionated
      radiotherapy.
AB  - A 54-year-old female presented with multiple episodes of emesis, intractable
      headaches, worsening balance, and slowly progressive right facial weakness.
      Imaging demonstrated a 3-cm mass in the left internal capsule and corona radiata
      region with associated edema, mass effect, and midline shift concerning for high
      grade glioma, lymphoma, or brain metastasis. Stereotactic biopsy of the mass was
      consistent with amyloid deposition. Systemic workup for amyloidosis was negative,
      and the mass was thought to represent a focal tumor-like deposit of amyloid, also
      referred to as "amyloidoma." In the absence of systemic disease, therapy, which
      can include surgery or radiotherapy, can be directed at the local process. The
      location of the patient's lesion was not amenable to resection; therefore, she
      was treated with fractionated radiotherapy of 30.6 Gy at 1.8 Gy per fraction.
      Serial brain MRI demonstrated stability 18 months out from therapy. To the
      authors' knowledge, this is the first documented case of focal fractionated
      radiotherapy for CNS amyloidoma. The authors concluded that radiotherapy can
      prevent further progression of amyloidomas in anatomical locations that prohibit
      resection.

PMID- 27689462
TI  - Occipital transtentorial/falcine approach, a "cross-court" trajectory to
      accessing contralateral posterior thalamic lesions: case report.
AB  - Surgical treatment of lesions in the posterior thalamus, especially those
      extending laterally, is technically challenging because of a deep surgical field,
      narrow operative corridor, and the surrounding critical neurovascular structures.
      The authors describe an occipital transtentorial/falcine approach (OTFA) that was
      successfully used in the treatment of a cavernous malformation (CM) extending
      laterally from thalamus to midbrain. A 40-year-old man complained of progressive
      right hemiparesis and numbness. Radiological evaluation revealed a large CM in
      the left thalamus, surfacing on the pulvinar thalami, and extending 4 cm
      laterally from the midline. In addition to the usual procedures of a right-sided
      occipital transtentorial approach, the authors incised the falx cerebri to expand
      the operative corridor to the left thalamus. They achieved generous exposure of
      the left thalamus through a "cross-court" oblique trajectory while avoiding
      excessive retraction on the occipital lobe. The CM was completely removed, and no
      newly developed or worsening deficits were detected postoperatively. To better
      understand the OTFA and its application, the authors performed a cadaveric
      dissection. The OTFA provides increased exposure of the posterior thalamus
      without cortical incision and facilitates lateral access to this area through the
      "cross-court" operative corridor. This approach adds to the armamentarium for
      neurosurgeons treating thalamic lesions.

PMID- 27689461
TI  - Stereotactic radiosurgery for cerebellar arteriovenous malformations: an
      international multicenter study.
AB  - OBJECTIVE Cerebellar arteriovenous malformations (AVMs) represent the majority of
      infratentorial AVMs and frequently have a hemorrhagic presentation. In this
      multicenter study, the authors review outcomes of cerebellar AVMs after
      stereotactic radiosurgery (SRS). METHODS Eight medical centers contributed data
      from 162 patients with cerebellar AVMs managed with SRS. Of these patients, 65%
      presented with hemorrhage. The median maximal nidus diameter was 2 cm. Favorable
      outcome was defined as AVM obliteration and no posttreatment hemorrhage or
      permanent radiation-induced complications (RICs). Patients were followed
      clinically and radiographically, with a median follow-up of 60 months (range 7
      325 months). RESULTS The overall actuarial rates of obliteration at 3, 5, 7, and
      10 years were 38.3%, 74.2%, 81.4%, and 86.1%, respectively, after single-session
      SRS. Obliteration and a favorable outcome were more likely to be achieved in
      patients treated with a margin dose greater than 18 Gy (p < 0.001 for both),
      demonstrating significantly better rates (83.3% and 79%, respectively). The rate
      of latency preobliteration hemorrhage was 0.85%/year. Symptomatic post-SRS RICs
      developed in 4.5% of patients (n = 7). Predictors of a favorable outcome were a
      smaller nidus (p = 0.0001), no pre-SRS embolization (p = 0.003), no prior
      hemorrhage (p = 0.0001), a higher margin dose (p = 0.0001), and a higher maximal
      dose (p = 0.009). The Spetzler-Martin grade was not found to be predictive of
      outcome. The Virginia Radiosurgery AVM Scale score (p = 0.0001) and the
      Radiosurgery-Based AVM Scale score (p = 0.0001) were predictive of a favorable
      outcome. CONCLUSIONS SRS results in successful obliteration and a favorable
      outcome in the majority of patients with cerebellar AVMs. Most patients will
      require a nidus dose of higher than 18 Gy to achieve these goals. Radiosurgical
      and not microsurgical scales were predictive of clinical outcome after SRS.

PMID- 27689463
TI  - Association between shunt-responsive idiopathic normal pressure hydrocephalus and
      alcohol.
AB  - OBJECTIVE Idiopathic normal pressure hydrocephalus (iNPH) is characterized by
      ventriculomegaly, gait difficulty, incontinence, and dementia. The symptoms can
      be ameliorated by CSF drainage. The object of this study was to identify factors
      associated with shunt-responsive iNPH. METHODS The authors reviewed the medical
      records of 529 patients who underwent shunt placement for iNPH at their
      institution between July 2001 and March 2015. Variables associated with shunt
      responsive iNPH were identified using bivariate and multivariate analyses.
      Detailed alcohol consumption information was obtained for 328 patients and was
      used to examine the relationship between alcohol and shunt-responsive iNPH. A
      computerized patient registry from 2 academic medical centers was queried to
      determine the prevalence of alcohol abuse among 1665 iNPH patients. RESULTS
      Bivariate analysis identified associations between shunt-responsive iNPH and gait
      difficulty (OR 4.59, 95% CI 2.32-9.09; p < 0.0001), dementia (OR 1.79, 95% CI
      1.14-2.80; p = 0.01), incontinence (OR 1.77, 95% CI 1.13-2.76; p = 0.01), and
      alcohol use (OR 1.98, 95% CI 1.23-3.16; p = 0.03). Borderline significance was
      observed for hyperlipidemia (OR 1.56, 95% CI 0.99-2.45; p = 0.054), a family
      history of hyperlipidemia (OR 3.09, 95% CI 0.93-10.26, p = 0.054), and diabetes
      (OR 1.83, 95% CI 0.96-3.51; p = 0.064). Multivariate analysis identified
      associations with gait difficulty (OR 3.98, 95% CI 1.81-8.77; p = 0.0006) and
      alcohol (OR 1.94, 95% CI 1.10-3.39; p = 0.04). Increased alcohol intake
      correlated with greater improvement after CSF drainage. Alcohol abuse was 2.5
      times more prevalent among iNPH patients than matched controls. CONCLUSIONS
      Alcohol consumption is associated with the development of shunt-responsive iNPH.

PMID- 27689464
TI  - Letter to the Editor: Neurosurgery skills training laboratories and curriculum: a
      supplement to Halstedian practice.

PMID- 27689465
TI  - Relationship of A1 segment hypoplasia to anterior communicating artery aneurysm
      morphology and risk factors for aneurysm formation.
AB  - OBJECTIVE Hypoplasia of the A1 segment of the anterior cerebral artery is
      frequently observed in patients with anterior communicating artery (ACoA)
      aneurysms. The effect of this anatomical variant on ACoA aneurysm morphology is
      not well understood. METHODS Digital subtraction angiography images were reviewed
      for 204 patients presenting to the authors' institution with either a ruptured or
      an unruptured ACoA aneurysm. The ratio of the width of the larger A1 segment to
      the smaller A1 segment was calculated. Patients with an A1 ratio greater than 2
      were categorized as having A1 segment hypoplasia. The relationship of A1 segment
      hypoplasia to both patient and aneurysm characteristics was then assessed.
      RESULTS Of 204 patients that presented with an ACoA aneurysm, 34 (16.7%) were
      found to have a hypoplastic A1. Patients with A1 segment hypoplasia were less
      likely to have a history of smoking (44.1% vs 62.9%, p = 0.0410). ACoA aneurysms
      occurring in the setting of a hypoplastic A1 were also found to have a larger
      maximum diameter (mean 7.7 vs 6.0 mm, p = 0.0084). When considered as a
      continuous variable, increasing A1 ratio was associated with decreasing aneurysm
      dome-to-neck ratio (p = 0.0289). There was no significant difference in the
      prevalence of A1 segment hypoplasia between ruptured and unruptured aneurysms
      (18.9% vs 10.7%; p = 0.1605). CONCLUSIONS Our results suggest that a hypoplastic
      A1 may affect the morphology of ACoA aneurysms. In addition, the relative lack of
      traditional risk factors for aneurysm formation in patients with A1 segment
      hypoplasia argues for the importance of hemodynamic factors in the formation of
      ACoA aneurysms in this anatomical setting.

PMID- 27689467
TI  - Problem Features versus Algorithm Performance on Rugged Multiobjective
      Combinatorial Fitness Landscapes.
AB  - In this article, we attempt to understand and to contrast the impact of problem
      features on the performance of randomized search heuristics for black-box
      multiobjective combinatorial optimization problems. At first, we measure the
      performance of two conventional dominance-based approaches with unbounded archive
      on a benchmark of enumerable binary optimization problems with tunable
      ruggedness, objective space dimension, and objective correlation ([Formula: see
      text]MNK-landscapes). Precisely, we investigate the expected runtime required by
      a global evolutionary optimization algorithm with an ergodic variation operator
      (GSEMO) and by a neighborhood-based local search heuristic (PLS), to identify a
      ([Formula: see text]approximation of the Pareto set. Then, we define a number of
      problem features characterizing the fitness landscape, and we study their
      intercorrelation and their association with algorithm runtime on the benchmark
      instances. At last, with a mixed-effects multilinear regression we assess the
      individual and joint effect of problem features on the performance of both
      algorithms, within and across the instance classes defined by benchmark
      parameters. Our analysis reveals further insights into the importance of
      ruggedness and multimodality to characterize instance hardness for this family of
      multiobjective optimization problems and algorithms.

PMID- 27689468
TI  - Performance Analysis of Continuous Black-Box Optimization Algorithms via
      Footprints in Instance Space.
AB  - This article presents a method for the objective assessment of an algorithm's
      strengths and weaknesses. Instead of examining the performance of only one or
      more algorithms on a benchmark set, or generating custom problems that maximize
      the performance difference between two algorithms, our method quantifies both the
      nature of the test instances and the algorithm performance. Our aim is to gather
      information about possible phase transitions in performance, that is, the points
      in which a small change in problem structure produces algorithm failure. The
      method is based on the accurate estimation and characterization of the algorithm
      footprints, that is, the regions of instance space in which good or exceptional
      performance is expected from an algorithm. A footprint can be estimated for each
      algorithm and for the overall portfolio. Therefore, we select a set of features
      to generate a common instance space, which we validate by constructing a
      sufficiently accurate prediction model. We characterize the footprints by their
      area and density. Our method identifies complementary performance between
      algorithms, quantifies the common features of hard problems, and locates regions
      where a phase transition may lie.

PMID- 27689466
TI  - Activation of estrogen receptor alpha by estradiol and cisplatin induces platinum
      resistance in ovarian cancer cells.
AB  - Activation of Estrogen receptor (ER) alpha (alpha) promotes cell growth and
      influences the response of cancer cell to chemotherapeutic agents. However, the
      mechanism by which ERalpha activation antagonizes cells to chemotherapy-induced
      cytotoxicity remains unclear. Here, we investigated the effect of cisplatin on
      ERalpha activation. In addition, we examined whether down-regulation of ERalpha
      modulate cisplatin-mediated cytotoxicity using 2 human ovarian cancer cells (Caov
      3 and Ovcar-3) transduced with ERalpha short hairpin RNA (shRNA). The
      proliferation assay showed that 17beta-estradiol (E2) induced cell proliferation
      via activation of Akt and extracellular signal-regulated kinase (ERK) cascades,
      while shRNA mediated downregulation of ERalpha inhibited the cell proliferation.
      Immunoblot analysis revealed that cisplatin induced the phosphorylation of
      ERalpha at serine 118 via ERK cascade. Luciferase assay showed that cisplatin
      increases transcriptional activity of estrogen-responsive element (ERE). The E2
      stimulated ERalpha activation attenuated cisplatin-induced cytotoxicity.
      Meanwhile, down-regulation of ERalpha inhibited E2-induced protective effect on
      cisplatin toxicity as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays. Moreover, Pretreatment with E2 followed
      by cisplatin decreased the expression of cleaved PARP, and increased the
      expression of anti-apoptotic protein Bcl-2. Collectively, our findings suggest
      that activation of ERalpha by E2 and cisplatin can induce platinum-resistance by
      increasing the expression of anti-apoptotic protein in ovarian cancer cells.
      Therefore, our findings provide valuable information that ERalpha might be a
      promising therapeutic target for platinum-resistant ovarian cancer.

PMID- 27689469
TI  - ?

PMID- 27689470
TI  - Normobaric Hypoxia Effects on Balance Measured by Computerized Dynamic
      Posturography.
AB  - : Wagner, Dale R., Skyler Saunders, Brady Robertson, and John E. Davis.
      Normobaric hypoxia effects on balance measured by computerized dynamic
      posturography. High Alt Med Biol. 17:222-227, 2016.-Background/Aim: Equilibrium
      was measured by computerized dynamic posturography at varying levels of
      normobaric hypoxia before and after exercise. METHODS: Following a
      familiarization trial, 12 males (27.3 +/- 7.1 years) completed three sessions in
      random order on a NeuroCom SMART Balance Master: a sham trial at the ambient
      altitude of 1500 m and simulated altitudes of 3000 and 5000 m created by a
      hypoxic generator. The NeuroCom provided composite scores for a sensory
      organization test of equilibrium and a motor control test to assess the
      appropriate motor response. Additional information on somatosensory, visual, and
      vestibular responses was obtained. Each session consisted of 20 minutes of rest
      followed by the NeuroCom test, then 10 minutes of exercise, and 10 minutes of
      recovery followed by a second NeuroCom test, all while connected to the hypoxic
      generator. Mean differences were identified with a two-way (pre/postexercise and
      altitude condition), repeated-measures analysis of variance. RESULTS: The
      composite sensory score was significantly lower (p < 0.001) during the 5000 m
      trial (73.4 +/- 12.0) compared to the 1500 m (80.8 +/- 7.0) and 3000 m (84.1 +/-
      5.0) altitudes. The inability to ignore inaccurate visual cues in a situation of
      visual conflict was the most common sensory error. Motor control was not affected
      by altitude or exercise. DISCUSSION: These results suggest that moderate hypoxia
      does not affect balance, but severe hypoxia significantly reduces equilibrium.
      Furthermore, it appears that the alterations in equilibrium are primarily from
      impairments in visual function.

PMID- 27689471
TI  - Letter to the Editor re: "Bicarbonate Values for Healthy Residents Living in
      Cities Above 1500 Meters of Altitude: A Theoretical Model and Systematic Review"
      by Ramirez-Sandoval et al. (High Alt Med Biol 2016;17:85-92).

PMID- 27689472
TI  - Professor Almaz A. Aldashev (1953-2016).

PMID- 27689474
TI  - Phthalates exposure indicators determined by urinary phthalate metabolites in
      healthy non-obese Czech adults: FANTOM study.
AB  - It is assumed that human exposure to phthalates may be associated with adverse
      health effects. The indicators of urinary phthalate metabolite concentrations in
      healthy adults are limited. In this study, the phthalate metabolites
      concentrations were detected from 24-h urine collection in non-obese Czech adults
      (n = 201). Each participant filled in an 80-item questionnaire (FANTOM-SQ 2013)
      regarding the outdoor and indoor sources of phthalates, the use of personal care
      products and food intake sources. The concentrations of 15 phthalates metabolites
      were analysed following enzymatic cleavage of the glucuronide using ultra-high
      performance liquid chromatography-electrospray ionisation tandem mass
      spectrometry (UHPLC-ESI-MS/MS). The indicators of chronic or acute exposure
      phthalate-containing materials were identified. It is shown that higher fruit
      consumption was positively and significantly associated with a higher level of
      total 15 urinary phthalates biomarkers (p < 0.001). Regular meat consumption
      showed a negative significant association with total 15 phthalates metabolites (p
      < 0.01). The use of personal care products was significantly and positively
      correlated with monoethyl phthalate urine concentrations (p < 0.05). The analysis
      of the dietary behaviour and personal care products use in the Czech non-obese
      population showed it to be a predictable tool in the level of phthalates exposure
      when high fruit consumption and personal care products use are linked to higher
      phthalate metabolite contents in the urine. However, this topic deserves more
      research.

PMID- 27689473
TI  - Altered microRNA expression profiles in lung damage induced by nanosized SiO2.
AB  - The objective of the present research is to explore miRNAs expression profiles in
      lung tissue of rat treated by nanosized SiO2 in the light of normal at diverse
      dosages, time, predict their target genes, and probe the biological function and
      regulation of miRNA in the lung damage process caused by nanosized SiO2. Up
      regulation of rno-miR-208, rno-miR-212 and rno-miR-18a in lung tissue mainly
      characterized by inflammation of SD rats caused by nanosized SiO2 particles
      instilled intratracheally at 7th, 15th 30th d using Illumina HiSeq2000 sequencing
      technique and were further verified by quantitative reverse transcriptase
      polymerase chain reaction (qRT PCR) assay. Lung damage is mainly with
      characteristics of lung interstitial fibrosis, upregulation of rno-miR-212, rno
      miR-144, rno-miR-702-3p, rno-miR-379 and rno-miR-127, down-regulation of rno-miR
      541 at 60th, 90th d post-exposure. As target genes of rno-miR-208, rno-miR-212
      and rno-miR-18a respectively, there was no statistical significance of programmed
      cell death 4 (PDCD4), LIN28B and connective tissue growth factor (CTGF) mRNA
      expression level (P > 0.05) compared to beta-actin as internal controls detected
      by Real-time quantitative PCR. The differences in protein gray value ratio of
      PDCD4, LIN28B and CTGF detected by Western blotting test were statistically
      significant (P < 0.05). These results suggested that miR-208, miR-212 and miR-18a
      may take effects in rats' lung damage lead by nanosized SiO2. Their target genes
      of PDCD4, LIN28B and CTGF functioned in translation level of target genes in
      regulation of inflammatory signaling pathways and involved in the formation of
      tissue fibrosis.

PMID- 27689475
TI  - CDO1 promoter methylation is associated with gene silencing and is a prognostic
      biomarker for biochemical recurrence-free survival in prostate cancer patients.
AB  - Molecular biomarkers may facilitate the distinction between aggressive and
      clinically insignificant prostate cancer (PCa), thereby potentially aiding
      individualized treatment. We analyzed cysteine dioxygenase 1 (CDO1) promoter
      methylation and mRNA expression in order to evaluate its potential as prognostic
      biomarker. CDO1 methylation and mRNA expression were determined in cell lines and
      formalin-fixed paraffin-embedded prostatectomy specimens from a first cohort of
      300 PCa patients using methylation-specific qPCR and qRT-PCR. Univariate and
      multivariate Cox proportional hazards and Kaplan-Meier analyses were performed to
      evaluate biochemical recurrence (BCR)-free survival. Results were confirmed in an
      independent second cohort comprising 498 PCa cases. Methylation and mRNA
      expression data from the second cohort were generated by The Cancer Genome Atlas
      (TCGA) Research Network by means of Infinium HumanMethylation450 BeadChip and
      RNASeq. CDO1 was hypermethylated in PCa compared to normal adjacent tissues and
      benign prostatic hyperplasia (P < 0.001) and was associated with reduced gene
      expression (rho = -0.91, P = 0.005). Using two different methodologies for
      methylation quantification, high CDO1 methylation as continuous variable was
      associated with BCR in univariate analysis (first cohort: HR = 1.02, P = 0.002,
      95% CI [1.01-1.03]; second cohort: HR = 1.02, P = 0.032, 95% CI [1.00-1.03]) but
      failed to reach statistical significance in multivariate analysis. CDO1 promoter
      methylation is involved in gene regulation and is a potential prognostic
      biomarker for BCR-free survival in PCa patients following radical prostatectomy.
      Further studies are needed to validate CDO1 methylation assays and to evaluate
      the clinical utility of CDO1 methylation for the management of PCa.

PMID- 27689476
TI  - Healthy Futures Program and Adolescent Sexual Behaviors in 3 Massachusetts
      Cities: A Randomized Controlled Trial.
AB  - OBJECTIVES:  We evaluated the impact of the 3-year Healthy Futures program on
      reducing sexual behaviors among middle school students. METHODS:  Fifteen public
      middle schools in Haverhill, Lowell, and Lynn, Massachusetts, participated in
      this longitudinal school-cluster randomized controlled trial (2011-2015), which
      included 1344 boys and girls. We collected student survey data at baseline,
      immediately after each Nu-CULTURE curriculum (classroom component of Healthy
      Futures) in the sixth, seventh, and eighth grades, and at a 1-year follow-up in
      the ninth grade (cohort 1 students only). RESULTS:  Healthy Futures did not
      reduce the overall prevalence of eighth-grade students who reported ever having
      vaginal sex. In the eighth-grade follow-up, fewer girls in the treatment group
      than in the control group reported ever having vaginal sex (P = .04), and fewer
      Hispanic treatment students than Hispanic control students reported ever having
      vaginal sex (P = .002). CONCLUSIONS:  There was some evidence of delaying sexual
      initiation by the end of Nu-CULTURE, for girls and Hispanics, but not for boys.
      Future research should focus on improving implementation of the supplemental
      components intended to foster interpersonal and environmental protective factors
      associated with sustained delays in sexual activity.

PMID- 27689477
TI  - Culturally Responsive Adolescent Pregnancy and Sexually Transmitted Infection
      Prevention Program for Middle School Students in Hawai'i.
AB  - OBJECTIVES:  To evaluate the effectiveness of Pono Choices, a culturally
      responsive adolescent pregnancy and sexually transmitted infection (STI)
      prevention program targeting middle school youths in Hawai'i. METHODS:  We
      conducted a cluster randomized controlled trial with the school as the unit of
      random assignment over 3 semesters between 2012 and 2013. The sample consisted of
      36 middle schools and 2203 students. We administered student surveys to collect
      baseline outcomes, student demographic data, and outcomes at 12 months after
      baseline. RESULTS:  We found statistically significant effects for the knowledge
      assessment, which focused on basic understanding of adolescent pregnancy and STI
      prevention. The average percentage of correct responses was 73.6 for the
      treatment group and 60.4 for the control group (P < .001). We did not find
      statistically significant effects on behavioral outcomes (initiation of sexual
      activity or engagement in high-risk sexual behavior) or on other nonbehavioral
      outcomes (attitudes, skills, intentions). CONCLUSIONS:  Pono Choices had a
      statistically significant impact on knowledge of adolescent pregnancy and STI
      prevention among middle school students at 12 months after baseline, though it
      did not lead to detectable changes in behavioral outcomes within the 1-year
      observation period. These results call for an exploration of longer-term outcomes
      to assess effects on knowledge retention and behavioral changes.

PMID- 27689478
TI  - Text Messaging, Teen Outreach Program, and Sexual Health Behavior: A Cluster
      Randomized Trial.
AB  - OBJECTIVES: To consider whether Youth All Engaged! (a text message intervention)
      intensified the effects of the adolescent pregnancy prevention Teen Outreach
      Program (control) for youths. METHODS: In this trial performed in Denver,
      Colorado, from 2011 to 2014, we randomized 8 Boys & Girls Clubs each of 4 years
      into 32 clubs per year combinations to ensure each club would serve as a
      treatment site for 2 years and a control site for 2 years. Control intervention
      consisted of the Teen Outreach Program only. We enrolled 852 youths (aged 14-18
      years), and 632 were retained at follow-up, with analytic samples ranging from 50
      to 624 across outcomes. We examined program costs, and whether the intervention
      increased condom and contraceptive use, access to care, and pregnancy prevention.
      RESULTS: Control program costs were $1184 per participant, and intervention costs
      were an additional $126 per participant (+10.6%). There were no statistically
      significant differences in primary outcomes for the full sample. Hispanic
      participants in the intervention condition had fewer pregnancies at follow-up
      (1.79%) than did those in the control group (6.72%; P = .02). CONCLUSIONS: Youth
      All Engaged is feasible, low cost, and could have potential benefits for Hispanic
      youths.

PMID- 27689479
TI  - Impacts of an Enhanced Family Health and Sexuality Module of the HealthTeacher
      Middle School Curriculum: A Cluster Randomized Trial.
AB  - OBJECTIVES:  To evaluate the impacts of an enhanced version of the Family Life
      and Sexuality Module of the HealthTeacher middle school curriculum. METHODS:  We
      conducted a cluster randomized trial of Chicago, Illinois, middle schools. We
      randomly assigned schools to a treatment group that received the intervention
      during the 2010-2011 school year or a control group that did not. The primary
      analysis sample included 595 students (7 schools) in the treatment group and 594
      students (7 schools) in the control group. RESULTS:  Students in the treatment
      schools reported greater exposure to information on reproductive health topics
      such as sexually transmitted infections (STIs; 78% vs 60%; P < .01), abstinence
      (64% vs 37%; P < .01), and birth control (45% vs 29%; P < .01). They also
      reported higher average scores on an index of knowledge of contraceptive methods
      and STI transmission (0.5 vs 0.3; P = .02). We found no statistically significant
      differences in rates of sexual intercourse (12% vs 12%; P = .99), oral sex (12%
      vs 9%; P = .18), or other intermediate outcomes. CONCLUSIONS:  The program had
      modest effects when tested among Chicago middle school students.

PMID- 27689480
TI  - Evaluation of the Be the Exception Sixth-Grade Program in Rural Communities to
      Delay the Onset of Sexual Behavior.
AB  - OBJECTIVES:  To investigate the impact of Be the Exception, a newly developed
      program to delay onset of sexual behaviors, in a White, rural population.
      METHODS:  A cluster randomized controlled trial in northwestern Indiana (14
      schools, 1776 students, 2011-2015) compared an intervention (5 group sessions and
      multimedia assembly) with a no-intervention group; both continued usual standard
      health education. Multilevel mixed-effects logistic regressions with 1455
      students measured long-term outcomes 12 months after baseline questionnaire.
      RESULTS:  Intervention group students reported ever having had sexual intercourse
      and sexual intercourse in past 3 months significantly less often than did the
      comparison group (1.91% vs 6.29% and 1.09% vs 4.26%, respectively). No
      statistical differences were observed for reported sexual intercourse in past 3
      months with risky behavior (1.23% vs 2.24%), without condom use (1.04% vs 1.73%),
      or without birth control (1.00% vs 1.53%). Cumulatively, intervention group
      students significantly more often reported no activity, holding hands, hugging
      and kissing and less often reported touching above and below the waist, other
      sex, or sexual intercourse. CONCLUSIONS:  Be the Exception is effective in
      delaying the onset of sexual behavior among rural middle school students.

PMID- 27689481
TI  - Comprehensive Reporting of Adolescent Pregnancy Prevention Programs.

PMID- 27689482
TI  - Replication Typology and Guidelines for Adolescent Pregnancy Prevention
      Initiatives.

PMID- 27689483
TI  - The Promise of Technology to Advance Rigorous Evaluation of Adolescent Pregnancy
      Prevention Programs in American Indian and Alaska Native Tribal Communities.

PMID- 27689484
TI  - Exploring Alternative Outcome Measures to Improve Pregnancy Prevention
      Programming in Younger Adolescents.

PMID- 27689485
TI  - Establishing an Evaluation Technical Assistance Contract to Support Studies in
      Meeting the US Department of Health and Human Services Evidence Standards.

PMID- 27689486
TI  - A Framework for Evaluation Technical Assistance.

PMID- 27689487
TI  - Challenges and Lessons Learned From Providing Large-Scale Evaluation Technical
      Assistance to Build the Adolescent Pregnancy Evidence Base.

PMID- 27689488
TI  - Adolescent Pregnancy Prevention Programs and Research: A Time To Revisit Theory.

PMID- 27689489
TI  - Video for Adolescent Pregnancy Prevention: Promises, Challenges, and Future
      Directions.

PMID- 27689490
TI  - Scalability of an Evidence-Based Adolescent Pregnancy Prevention Program: New
      Evidence From 5 Cluster-Randomized Evaluations of the Teen Outreach Program.
AB  - OBJECTIVES:  To determine if the Teen Outreach Program (TOP), a youth development
      and service learning program, can reduce sexual risk-taking behaviors compared
      with a business as usual or benign counterfactual. METHODS:  We synthesized
      results of 5 independent studies conducted in 5 geographically and ethnically
      diverse locations between 2011 and 2015 with 17 194 middle and high school
      students. Each study cluster-randomized classes, teachers, or schools to
      treatment or control groups and included the students enrolled in those clusters
      at baseline in an intent-to-treat analysis. Multilevel models tested impacts on
      recent sexual activity, recent unprotected sexual activity, and sexual initiation
      among the sexually inexperienced at baseline at approximately 1 and 2 years after
      baseline. RESULTS:  Precision-weighted average effect sizes showed nonsignificant
      reductions of 1 percentage point or less in recent sexual activity (5 studies: 
      0.6; P = .32), recent unprotected sex (5 studies: -0.2; P = .76), and sexual
      initiation (4 studies: -1.1; P = .10) after 1 year. CONCLUSIONS:  There was
      little evidence of the effectiveness of TOP in reducing sexual risk-taking
      behaviors. Results underscored the importance of continually evaluating evidence
      based programs that have previously been shown to be effective.

PMID- 27689491
TI  - Randomized Trials of the Teen Outreach Program in Louisiana and Rochester, New
      York.
AB  - OBJECTIVES:  To evaluate the Teen Outreach Program, a pregnancy prevention
      program, in 2 community-based settings. METHODS:  We evaluated the Teen Outreach
      Program, a 9-month positive youth development program, in 3 cohorts of youths
      from 2012 to 2015 in 2 states. In Louisiana, 7 agencies participated in an
      individualized randomized controlled trial, with youths randomly assigned to a
      treatment or control condition. Fourteen agencies in Rochester, New York,
      participated in a cluster randomized controlled trial. RESULTS:  We found no
      differences between the intervention and control youths on delay of sexual onset
      in Louisiana (adjusted odds ratio [AOR] = 0.80; 95% confidence interval [CI] =
      0.62, 1.03) or in Rochester, New York (AOR = 0.89; 95% CI = 0.45, 1.77), or for
      sex with no effective means of birth control (Louisiana, AOR = 1.18; 95% CI =
      0.78, 1.78; Rochester, AOR = 0.41; 95% CI = 0.13, 1.27) after controlling for
      relevant covariates. CONCLUSIONS:  We found no short-term effects for the offer
      of the intervention. Research might be needed for the long-term and intermediate
      impacts of youth development programs on these and other adolescent risk
      behaviors.

PMID- 27689492
TI  - Replicating Reducing the Risk: 12-Month Impacts of a Cluster Randomized
      Controlled Trial.
AB  - OBJECTIVES:  To test the effectiveness of Reducing the Risk, an evidence-based
      sexual health curriculum designed to help prevent adolescent pregnancy and
      sexually transmitted infections, on youth sexual behavior and intermediate
      outcomes thought to lead to these behaviors. METHODS:  Classes within schools in
      St. Louis, Missouri; Austin, Texas; and San Diego, California; were randomly
      assigned to receive Reducing the Risk or "business as usual." Youths completed
      Web-based surveys at baseline (preintervention, August 2012-January 2014) and 12
      months later (August 2013-January 2015). Intent-to-treat analyses were conducted
      across sites; we tested for differences in impacts between sites and other
      subgroups. RESULTS:  The program had no overall impact on sexual behaviors.
      However, at 1 site, program participants were significantly less likely to have
      engaged in recent sexual intercourse than were control group members. There were
      positive overall impacts on intermediate outcomes (e.g., knowledge, attitudes).
      CONCLUSIONS:  After 12 months, Reducing the Risk was unsuccessful at changing
      sexual behaviors. Other results were mixed, but promising evidence (e.g.,
      behavioral impacts at 1 site, impacts on intermediate outcomes) suggests
      potential for more widespread behavioral impacts over a longer term.

PMID- 27689493
TI  - Building the Evidence to Prevent Adolescent Pregnancy.

PMID- 27689494
TI  - Replicating the Safer Sex Intervention: 9-Month Impact Findings of a Randomized
      Controlled Trial.
AB  - OBJECTIVES:  To test the effects of the Safer Sex Intervention (SSI) on female
      adolescents' sexual behavior and possible antecedents of behavior such as sexual
      health attitudes, knowledge, motivation, intentions, and skills. METHODS:  A
      randomized controlled trial compared SSI (n = 1196) with no intervention (n =
      613) among female adolescents aged 13 to 20 years at 3 sites across the United
      States from 2012 to 2015. Intent-to-treat impacts were estimated at 9 months
      after baseline, overall, and for key subgroups. RESULTS:  Compared with control
      participants, SSI participants were less likely to have sexual intercourse
      without birth control, more likely to report positive attitudes toward protection
      and intention to use condoms, and more confident of their ability to refuse sex.
      SSI did not affect sexual risk knowledge or motivation to delay childbearing.
      Positive impacts on sexual behavior and sexual risk were observed among key
      subgroups of youths who were aged 18 years or older, Hispanic, not sexually
      experienced at baseline, and enrolled at the Minnesota site. CONCLUSIONS:  SSI
      produced meaningful changes in sexual behavior and sexual risk and successfully
      addressed some potential antecedents of sexual risk behavior.

PMID- 27689495
TI  - Building the Evidence to Prevent Adolescent Pregnancy: Contents of the Volume.

PMID- 27689496
TI  - It's Your Game...Keep It Real in South Carolina: A Group Randomized Trial
      Evaluating the Replication of an Evidence-Based Adolescent Pregnancy and Sexually
      Transmitted Infection Prevention Program.
AB  - OBJECTIVES:  To evaluate the effectiveness of an evidence-based HIV/sexually
      transmitted infection (STI)/pregnancy prevention program for middle schools
      implemented by school staff in South Carolina. METHODS:  Twenty-four schools,
      representing 3143 youths, participated in a randomized trial from 2011 to 2014.
      Students completed surveys before programming (fall of seventh grade), after
      completing the 2-year It's Your Game...Keep It Real program (spring of eighth
      grade), and 1-year postprogram (spring of ninth grade). RESULTS:  There was no
      statistically significant effect on initiation of vaginal sex between baseline
      and eighth grade. Significantly fewer students in the comparison condition
      reported initiating sex at ninth grade, relative to the intervention condition.
      No group differences existed on other behavioral outcomes that addressed sexual
      activity in the past 3 months at ninth grade. Seven of 26 psychosocial outcomes
      (3 knowledge, 1 attitude, 1 self-efficacy, 2 personal limits) were positively
      affected at eighth grade; 4 remained significant at ninth grade. CONCLUSIONS: 
      The original studies' behavioral effects were not replicated in this population,
      possibly as a result of this being an effectiveness trial instead of an efficacy
      trial, counterfactual exposure design issues, or postprogram exposure to evidence
      based programming.

PMID- 27689497
TI  - Informing The Evidence Base On Adolescent Pregnancy and Sexually Transmitted
      Infections: Important Lessons.

PMID- 27689498
TI  - Replicating !Cuidate!: 6-Month Impact Findings of a Randomized Controlled Trial.
AB  - OBJECTIVES:  To test whether !Cuidate!, a program culturally adapted for Hispanic
      youths, affects sexual risk behavior. METHODS:  We evaluated 3 replications of
      !Cuidate! in California, Arizona, and Massachusetts in a randomized controlled
      trial (registry no. NCT02540304) in which 2169 primarily Hispanic participants
      were randomly assigned to an intervention (n = 1326) or a control (n = 870)
      group. Youths were surveyed at baseline (September 2012-April 2014) and 6 months
      postbaseline (March 2013-October 2014). We estimated pooled and subgroup impacts
      using a regression framework with baseline covariates to increase statistical
      precision (1216 youths analyzed in the treatment group, 806 analyzed in the
      control group). RESULTS:  We found no impacts on the study's primary outcomes of
      recent sexual activity or recent unprotected sexual activity. However, !Cuidate!
      improved knowledge (10%-20% increase; P < .001), attitudes (effect size = .24; P
      < .001), and skills (effect size = .14; P = .002). Exploratory subgroup analyses
      suggest potentially problematic effects for some groups. CONCLUSIONS:  Findings
      suggest that !Cuidate! was effective in improving youths' knowledge and
      attitudes. However, after 6 months, these changes did not translate to
      improvements in reported sexual risk behaviors.

PMID- 27689499
TI  - Impact of an Intervention Designed to Reduce Sexual Health Risk Behaviors of
      African American Adolescents: Results of a Randomized Controlled Trial.
AB  - OBJECTIVES:  To replicate an evidence-based HIV risk reduction program and assess
      its impact on 2 behavioral outcomes-inconsistency of condom use and frequency of
      sex-6 months after the program. METHODS:  The study was an individual-level
      randomized controlled trial in which we randomly assigned 850 youths (aged 14-18
      years) to 1 of 2 conditions. The treatment (Becoming a Responsible Teen) is a
      group-level sociocognitive and skills training sexual education course; the
      control is a general health intervention that includes the same initial
      informational component as the treatment. Participants were recruited over 3
      summers (2012-2014) from a summer employment program in New Orleans, Louisiana,
      that serves primarily African American adolescents. RESULTS:  Six months after
      program exposure, we found no statistically significant difference between
      treatment and control group members' self-reported inconsistency of condom use or
      frequency of sex (P > .05). CONCLUSIONS:  Although previous evidence has
      indicated that this particular program can be effective, this study's findings
      indicate that it was not effective in this setting with this specific population.
      Results should provide an incentive to learn why the intervention works in some
      cases and what conditions are necessary for causal impacts.

PMID- 27689500
TI  - Impact of Two Adolescent Pregnancy Prevention Interventions on Risky Sexual
      Behavior: A Three-Arm Cluster Randomized Control Trial.
AB  - OBJECTIVES:  To test the efficacy of Reducing the Risk (RTR) and Love Notes (LN)
      on reducing risky sexual behavior among youths yet to experience or cause a
      pregnancy. METHODS:  The four dependent variables were ever had sex, condom use,
      birth control use, and number of sexual partners at 3- and 6-month follow-up in a
      3-arm cluster randomized controlled trial of 1448 impoverished youths, aged 14 to
      19 years, in 23 community-based organizations in Louisville, Kentucky, from
      September 2011 through March 2014. RESULTS:  At 3 and 6 months, compared with the
      control condition, youths in RTR reported fewer sexual partners and greater use
      of birth control. At 6 months, LN participants reported greater use of birth
      control and condoms, fewer sexual partners, and were less likely to have ever had
      sex compared with the control condition. CONCLUSIONS:  We provided additional
      evidence for the continued efficacy of RTR and the first rigorous study of LN,
      which embeds sex education into a larger curriculum on healthy relationships and
      violence prevention.

PMID- 27689501
TI  - The Teen Pregnancy Prevention Program (2010-2015): Synthesis of Impact Findings.

PMID- 27689502
TI  - A Clustered Randomized Controlled Trial of the Positive Prevention PLUS
      Adolescent Pregnancy Prevention Program.
AB  - OBJECTIVES:  To determine the impact of Positive Prevention PLUS, a school-based
      adolescent pregnancy prevention program on delaying sexual intercourse, birth
      control use, and pregnancy. METHODS:  I randomly assigned a diverse sample of
      ninth grade students in 21 suburban public high schools in California into
      treatment (n = 2483) and control (n = 1784) groups that participated in a
      clustered randomized controlled trial. Between October 2013 and May 2014,
      participants completed baseline and 6-month follow-up surveys regarding sexual
      behavior and pregnancy. Participants in the treatment group were offered Positive
      Prevention PLUS, an 11-lesson adolescent pregnancy prevention program. RESULTS: 
      The program had statistically significant impacts on delaying sexual intercourse
      and increasing the use of birth control. However, I detected no program effect on
      pregnancy rates at 6-month follow-up. CONCLUSIONS:  The Positive Prevention PLUS
      program demonstrated positive impacts on adolescent sexual behavior. This
      suggests that programs that focus on having students practice risk reduction
      skills may delay sexual activity and increase birth control use.

PMID- 27689503
TI  - Preventing Pregnancy in High School Students: Observations From a 3-Year
      Longitudinal, Quasi-Experimental Study.
AB  - OBJECTIVES:  To assess whether a sexual health education intervention reduces
      pregnancy rates in high school students. METHODS:  We performed a secondary
      analysis of a 3-year quasi-experimental study performed in South Texas from 2011
      to 2015 in which 1437 students without a history of pregnancy at baseline were
      surveyed each fall and spring. Potentially confounding risk factors considered
      included sexual behaviors, intentions, and demographics. The outcome measure was
      self-reported pregnancy status for male and female students. We performed
      analyses for male and female students using separate discrete time-to-event
      models. RESULTS:  We found no difference in pregnancy rates between intervention
      and comparison students within the first 3 years of high school. Female and male
      students in the intervention groups had pregnancy hazard ratios of, respectively,
      1.62 (95% CI = 0.9, 2.61; P = .1) and 0.78 (95% CI = 0.44, 1.48; P = .4) relative
      to the comparison groups. CONCLUSIONS:  The educational intervention had no
      impact on the pregnancy rate. Social media tools in pregnancy prevention programs
      should be adaptive to new technologies and rapidly changing adolescent
      preferences for these services.

PMID- 27689504
TI  - Cementless hip implants: an expanding choice.
AB  - INTRODUCTION: Total hip replacement is a successful procedure with long survival
      records compared to other joint arthroplasties. Cemented implants have been
      available for many years, however the complications associated with loosening
      and, ultimately, failure over time has led to the development of cementless stems
      and implants.The ideal prosthesis should recreate a biomechanically normal hip
      joint, allow pain-free function and last the patient's life span without
      requiring revision. Optimal results with uncemented femoral stems rely on
      obtaining initial stability, osseointegration, biological fixation, and uniform
      stress transfer to the proximal bone.There are a multitude of factors that can
      affect the integration, stability and fixation of these stems into bone, and
      understanding these factors is the key to choosing the appropriate implant for a
      specific femur. METHODS: This article aims to discuss cementless prostheses based
      on evidence-based practice. Geometry, roughness, stem coating, technique and bone
      quality are among the factors discussed. This was achieved through a review of
      the current literature. CONCLUSIONS: Uncemented femoral stems have shown good,
      long-term survivorship and functional outcome, with promising results in younger
      patients.Limitations in the current literature make it difficult to assess and
      compare different designs to determine optimal indications for each
      type.Biological fixation, in which the prosthesis is directly fixed to the bone,
      is the preferred fixation method.Future studies of cementless implants should
      consistently address patient age, activity level, bone type, and deformities so
      that more definitive conclusions can be drawn about when to use each design.

PMID- 27689505
TI  - Noise characteristics in ceramic-on-ceramic vs. metal-on-polyethylene total hip
      arthroplasty: a comparative study.
AB  - INTRODUCTION: A comparison of noise in ceramic-on-ceramic (CoC) bearings and
      metal-on-polyethylene (MoP) bearings after total hip arthroplasty (THA) was
      undertaken. Noise associated with MoP implants is rarely reported and has not
      been linked to squeaking. METHODS: A noise characterising hip questionnaire and
      Oxford Hip Score (OHS) was sent to 1,000 THA patients; there were 509 respondents
      282 CoC and 227 MoP; mean age 63.7 years (range 45-92 years), mean follow up 33
      months (range 6-156 months). RESULTS: Of 282 repsondents 47 (17%) of the CoC
      patients reported noise compared to 19 (8%) of the MoP patients (p = 0.048); 9
      CoC patients and 4 MoP patients reported squeaking. Overall, 27% patients with
      noise reported avoiding recreational activities because of it and patients with
      noisy hips scored on average 5 points less on the OHS (CoC: p = 0.04 and MoP: p =
      0.007). DISCUSSION: This is the first study to report squeaking from MoP THAs.
      The squeaking hip phenomenon is not exclusive to CoC THAs. Noisy hip implants may
      have social implications, and patients should be aware of this. We have shown a
      relationship between noise and a lower OHS. However, longer follow-up is needed
      to link noise to a poorly functioning implant.

PMID- 27689506
TI  - Erratum to: Assessing reproducibility for radiographic measurement of leg length
      inequality after total hip replacement, Hip Int. 2012 Sep-Oct;22(5):539-544.
AB  - Erratum to: Hip Int. 2012 Sep-Oct;22(5):539-544. Assessing reproducibility for
      radiographic measurement of leg length inequality after total hip replacement.
      McWilliams AB, Grainger AJ, O'Connor PJ, Redmond AC, Stewart TD, Stone MH. PMID:
      23100154 DOI:10.5301/HIP.2012.9751 [PubMed - indexed for MEDLINE] In the article
      "Assessing reproducibility for radiographic measurement of leg length inequality
      after total hip replacement", by Anthony B. McWilliams, Andrew J. Grainger,
      Philip J. O'Connor, Anthony C. Redmond, Todd D. Stewart, Martin H. Stone,
      published in Hip International 2012; 22 (5): 539-544, there is an error in the
      labelling of Figure 4. The radiograph of the CFR-T-LT method is incorrectly
      labelled. The S (or stem) measurement and the O (or overall) measurement should
      be switched. The text in the caption is corrected below. This is an error in
      labelling and makes no difference to the results of the study; the measurements
      and methodology remain unchanged and the authors stand by the results. Fig. 4 -
      The CFR-T-LT Method. An initial reference line is drawn between the centres of
      femoral rotation. Two further lines are drawn parallel to this. The first at the
      level of the most inferior part of the acetabular teardrop to give measurement C,
      which corresponds to any inequality (CA-CN) due to the position of the cup. The
      second is at the level of the centre of the lesser trochanter to give measurement
      S, which corresponds to inequality (SA-SN) due to position of the stem. The
      measurement between these two additional lines is the overall LLI, (OA-ON).

PMID- 27689507
TI  - Characterization of Glutamine Deamidation by Long-Length Electrostatic Repulsion
      Hydrophilic Interaction Chromatography-Tandem Mass Spectrometry (LERLIC-MS/MS) in
      Shotgun Proteomics.
AB  - Deamidation of glutamine (Gln) residues is a spontaneous or enzymatic process
      with significant implications in aging and human pathology. Although some methods
      are available to identify the gamma/alpha-glutamyl products of deamidation, none
      of these methods allows the characterization of this post-translational
      modification (PTM) from complex biological samples by shotgun proteomics. Here we
      present LERLIC-MS/MS, a chromatographic strategy that uses a long (50 cm) anion
      exchange capillary column operating in the electrostatic repulsion-hydrophilic
      interaction mode (ERLIC) and coupled directly to tandem mass spectrometry (MS/MS)
      for proteome analysis in a single injection. Profiling of soluble extracts of
      brain tissues by LERLIC-MS/MS distinguished for the first time gamma/alpha
      glutamyl isomers of deamidation, encountering a 1.7 gamma/alpha-glutamyl ratio
      for most Gln deamidation products. A detailed analysis of any deviation from that
      observed ratio allowed the identification of transglutaminase-mediated gamma
      glutamyl isomers as intermediate products of transamidation. Furthermore, LERLIC
      MS/MS was able to simultaneously separate Gln and asparagine (Asn) deamidation
      products even for those peptides showing multiple deamidated proteoforms. The
      characterization of Asn deamidated residues by LERLIC-MS/MS also uncovered novel
      PIMT (protein L-isoaspartyl methyltransferase) substrate proteins in human brain
      tissues that deviated from the expected 3:1 isoAsp/Asp ratio. Taken together, our
      results demonstrate that LERLIC-MS/MS can be used to perform an in-depth study of
      protein deamidation on a global proteome scale. This new strategy should help to
      elucidate the biological implications of deamidation in aging and disease
      conditions.

PMID- 27689509
TI  - Job control, work-family balance and nurses' intention to leave their profession
      and organization: A comparative cross-sectional survey.
AB  - BACKGROUND: The shortage of nurses is a problem in many countries. In Japan, the
      distribution of nurses across different care settings is uneven: the shortage of
      nurses in home healthcare and nursing homes is more serious than in hospitals.
      Earlier research has identified numerous factors affecting nurses' intention to
      leave work (e.g., job control, family-related variables, work-family conflict);
      however, these factors' levels and effect size may vary between nurses in
      hospitals, home healthcare, and nursing homes. OBJECTIVES: This study measured
      job control, family-related variables, and work-family conflict among nurses in
      hospitals, home healthcare, and nursing homes, and compared these variables'
      levels and effect size on nurses' intention to leave their organization or
      profession between these care settings. DESIGN: The research design was cross
      sectional. METHODS: Participating nurses from hospitals, home healthcare
      facilities, and nursing homes self-administered an anonymous questionnaire
      survey; nurses were recruited from the Kyushu district of Japan. Nurses from nine
      hospitals, 86 home healthcare offices, and 107 nursing homes participated. We
      measured nurses' intention to leave nursing or their organization, perceived job
      control, family variables and work-family conflict. We analyzed 1461 participants
      (response rate: 81.7%). RESULTS: The level of job control, family variables, and
      work-family conflict affecting nurses varied between hospitals, home healthcare,
      and nursing homes; additionally, these variables' effect on nurses' intention to
      leave their organization or profession varied between these care settings. Work
      family conflict, family variables, and job control most strongly predicted
      nurses' intention to leave their organization or profession in hospitals, home
      healthcare, and nursing homes, respectively. CONCLUSIONS: Interventions aiming to
      increase nurse retention should distinguish between care settings. Regarding
      hospitals, reducing nurses' work-family conflict will increase nurse retention.
      Regarding home healthcare, allowing nurses to fulfill family responsibilities
      will increase nurse retention. Regarding nursing home nurses, increasing nurses'
      job control will increase nurse retention.

PMID- 27689508
TI  - College students' perceptions and knowledge of hookah use.
AB  - PURPOSE: Hookah is an increasingly popular tobacco product among college
      students. The purpose of this study was to determine if college students are
      aware of tobacco and nicotine content in hookah, and examine associations between
      college students' knowledge and perceptions of hookah and their past 30-day
      hookah use. METHODS: Participants were 5451 young adults attending one of 24 2-
      and 4-year colleges. Analyses examined if hookah knowledge was uniquely
      associated with current hookah use, over and above perceptions of harm and
      addictiveness, number of other tobacco products currently used, and socio
      demographic factors. Analyses were first conducted for the entire sample and then
      only for current hookah users. RESULTS: 26.9% of all students believed hookah did
      not contain tobacco and 38% believed that hookah did not contain nicotine.
      Students who believed that hookah contained tobacco were at increased odds of
      hookah use, and those with increased perceptions of harm were at decreased odds
      of hookah use. However, hookah knowledge was not associated with hookah users'
      intensity of use. Moreover, although increased perceptions of harm were
      associated with lower intensity of use among current users, increased perceptions
      of addictiveness were associated with higher intensity of use. CONCLUSIONS: This
      study shows gaps in knowledge of hookah contents, and adds to the body of
      literature, which provides evidence for mandating warning labels as well as
      tobacco interventions for college students.

PMID- 27689510
TI  - Synthesis and Application of Organic Phosphonate Salts as Draw Solutes in Forward
      Osmosis for Oil-Water Separation.
AB  - The development of suitable draw solution in forward osmosis (FO) process has
      attracted the growing attention for water treatment purpose. In this study, a
      series of organic phosphonate salts (OPSs) are synthesized by one-step Mannich
      like reaction, confirmed by FTIR and NMR characterizations, and applied as novel
      draw solutes in FO applications. Their solution properties including osmotic
      pressures and viscosities, as well as their FO performance as a function of the
      solution concentration are investigated systematically. In FO process, a higher
      water flux of 47-54 LMH and a negligible reverse solute flux can be achieved in
      the PRO (AL-DS) mode (active layer faces the draw solution) using a homemade thin
      film composite membrane (PSF-TFC) and deionized water as the feed solution. Among
      all OPS draw solutes, the tetraethylenepentamine heptakis(methylphosphonic)
      sodium salt (TPHMP-Na) exhibits the best FO flux at 0.5 mol/kg concentration,
      which is further applied for the separation of emulsified oil-water mixture. The
      recovery of diluted OPS solutions is carried out via a nanofiltration (NF) system
      with a rejection above 92%. The aforementioned features show the great potential
      of OPS compounds as a novel class of draw solutes for FO applications.

PMID- 27689511
TI  - Integrating social and facial models of person perception: Converging and
      diverging dimensions.
AB  - Models of first impressions from faces have consistently found two underlying
      dimensions of trustworthiness and dominance. These dimensions show apparent
      parallels to social psychological models of inter-group perception that describe
      dimensions of warmth (cf. trustworthiness) and competence (cf. dominance), and it
      has been suggested that they reflect universal dimensions of social cognition. We
      investigated whether the dimensions from face and inter-group social perception
      models are indeed equivalent by evaluating first impressions of faces. Across
      four studies with differing methods we consistently found that while perceptions
      of trustworthiness and warmth were closely related, perceptions of dominance and
      competence were less strongly related. Taken together, our results demonstrate
      strong similarity on the first dimension across facial and social models, with
      less similarity on the second dimension. We suggest that facial impressions of
      competence and dominance may represent different routes to judging a stranger's
      capability to help or harm.

PMID- 27689512
TI  - Comparable rest-related promotion of spatial memory consolidation in younger and
      older adults.
AB  - Flexible spatial navigation depends on cognitive mapping, a function that
      declines with increasing age. In young adults, a brief period of postnavigation
      rest promotes the consolidation and integration of spatial memories into accurate
      cognitive maps. We examined (1) whether rest promotes spatial memory
      consolidation and integration in older adults; and (2) whether the magnitude of
      the rest benefit changes with increasing age. Young and older adults learned a
      route through a virtual environment, followed by a 10-minute delay comprising
      either wakeful rest or a perceptual task, and a subsequent cognitive mapping
      task, requiring the pointing to landmarks from different locations. Pointing
      accuracy was lower in the older than younger adults. However, there was a
      comparable rest-related enhancement in pointing accuracy in the 2 age groups.
      Together our findings suggest that (1) the age-related decline in cognitive
      mapping cannot be explained by increased consolidation interference in older
      adults; and (2) as we grow older, rest continues to support the consolidation and
      integration of spatial memories.

PMID- 27689513
TI  - A social network analysis of substance use among immigrant adolescents in six
      European cities.
AB  - BACKGROUND: Social integration and the health of adolescents with a migration
      background is a major concern in multicultural societies. The literature,
      however, has paid little attention to the wider determinants of their health
      behaviours, including the composition of their social networks. The aim of this
      study was to describe the composition of adolescents' social networks according
      to migration background, and to examine how social networks are associated with
      substance use. METHOD: In 2013, the SILNE study surveyed 11,015 secondary-school
      adolescents in 50 schools in six European cities in Belgium, Finland, Germany,
      Italy, the Netherlands, and Portugal, using a social network design. Each
      adolescent nominated up to five of their best and closest friends. Migration
      status was defined as first-generation migrants, second-generation migrants, and
      speaking another language at home. We computed two groups of network structural
      positions, the centrality of individual adolescents in networks, and the
      homophily of their social ties regarding migration (same-migration). Multilevel
      logistic regression was used to model the association between network structural
      position and smoking, alcohol use, and cannabis use. RESULTS: Compared with non
      migrant adolescents, adolescents with migration backgrounds had similar
      relationship patterns. But almost half their social ties were with same-migration
      background adolescents; non-migrants had few social ties to migrants. For
      adolescents with a migration background, a higher proportion of social ties with
      non-migrants was associated with increased use of cannabis (OR = 1.07, p = 0.03)
      and alcohol (OR = 1.08, p < 0.01), but not with increased smoking (p = 0.60).
      Popular migrant adolescents were at less risk of smoking, alcohol use, and
      cannabis use than popular non-migrant adolescents. CONCLUSION: Homophily of
      social ties by migration background is noticeable in European schools. The
      tendency of migrant adolescents to have same-migration social ties may isolate
      them from non-migrant adolescents, but also reduces their risky health
      behaviours, in particular cannabis and alcohol use.

PMID- 27689514
TI  - The second me: Seeing the real body during humanoid robot embodiment produces an
      illusion of bi-location.
AB  - Whole-body embodiment studies have shown that synchronized multi-sensory cues can
      trick a healthy human mind to perceive self-location outside the bodily borders,
      producing an illusion that resembles an out-of-body experience (OBE). But can a
      healthy mind also perceive the sense of self in more than one body at the same
      time? To answer this question, we created a novel artificial reduplication of
      one's body using a humanoid robot embodiment system. We first enabled individuals
      to embody the humanoid robot by providing them with audio-visual feedback and
      control of the robot head movements and walk, and then explored the self-location
      and self-identification perceived by them when they observed themselves through
      the embodied robot. Our results reveal that, when individuals are exposed to the
      humanoid body reduplication, they experience an illusion that strongly resembles
      heautoscopy, suggesting that a healthy human mind is able to bi-locate in two
      different bodies simultaneously.

PMID- 27689515
TI  - Presacral retroperitoneal hematoma after blunt trauma presents with rectal
      bleeding - A case report.
AB  - INTRODUCTION: We present a case of a presacral hematoma, which penetrated into
      the rectum resulting in rectal bleeding. This is an unusual presentation of a
      presacral hematoma. PRESENTATION OF THE CASE: A 76-year-old woman, using warfarin
      anticoagulant prophylaxis, presented with a rectal bleed two days after a fall. A
      sigmoidoscopy revealed that the source of bleeding was a presacral hematoma
      penetrating into the rectum. A Computed Tomography scan of the pelvis confirmed
      the presence of a hematoma measuring 10*9.4cm in the presacral space, as well as
      a fracture of os coccygis. She was transferred to a highly specialized facility,
      where she was treated conservatively with blood transfusions and repeated
      endoscopic toilet of the presacral cavity. One month after her initial fall, the
      patient had fully recovered. DISCUSSION: Rectal bleeding usually causes suspicion
      of a bleeding in the gastrointestinal tract. In this report the patient's
      anticoagulant treatment has likely contributed to bleeding and the formation of
      the hematoma. To our knowledge, this is the first case report of a presacral
      hematoma acutely penetrating into the rectum and causing lower gastrointestinal
      bleeding. CONCLUSION: Rectal bleed after trauma, in a patient receiving
      anticoagulant treatment, should raise suspicion of a penetrating hematoma, and
      such patients should be managed at highly specialized facilities.

PMID- 27689516
TI  - Granular cell tumour developing in the background of a previous mandibular giant
      cell lesion: Case report.
AB  - INTRODUCTION: Granular cell tumours of the mandible are very rare. We present a
      unique case which has developed at the site of a previous giant cell lesion.
      PRESENTATION: 51 year old Caucasian lady had excision of a recurrent giant cell
      lesion of the anterior mandible. Follow up showed evidence of radiographic
      recurrence. However, further biopsies from the same site showed granular cell
      tumour with soft tissues extension. The patient remains well on long term follow
      up with no evidence of recurrence. DISCUSSION: This case is unique because the
      granular cell tumour has evolved from the site of a recurrent giant cell lesion.
      Conservative surgical excision was an adequate treatment option. CONCLUSION:
      Within the limitations of our case study, a correlation between granular cell
      tumour and giant cell lesion is possible. However, more research is needed to
      prove this.

PMID- 27689517
TI  - Platelet-rich fibrin (PRF) in implant dentistry in combination with new bone
      regenerative technique in elderly patients.
AB  - INTRODUCTION: Some studies have demonstrated that platelet rich fibrin (PRF) is a
      healing biomaterial with a great potential for bone and soft tissue regeneration,
      without any inflammatory reactions and may be used alone or in combination with
      bone grafts, promoting hemostasis, bone growth, and maturation. PRF appears as a
      natural and satisfactory aid in bone regenerative surgery in elderly patients
      with favorable results and low risks. AIM: This study wants to demonstrate how
      PRF in association with a new split crest augmentation technique can be a great
      aid in implant rehabilitation, especially in the elderly patients, when bone
      regeneration is required. MATERIALS AND METHODS: Ten patients were treated in
      this study, five following the flapless split crest new procedure and other five
      patients following traditional procedure without split crest as control. Five
      patients with an average age between 50 and 60 years were selected to be operated
      with a split crest flapless modified technique in order to optimize the
      regenerative conditions with a bone augmentation and implant insertion in one
      single stage procedure. For all the patients autologous PRF has been used to fill
      the split crest gap or simply as regenerative material. Orthopantomography,
      intraoral radiography and CT DentaScan/CT Cone beam were performed for every
      patient before the treatment and at follow-up time exeption made for CT. RESULTS:
      All cases were successful, there were no problems at surgery time, at post
      operative and at osteointegration periods. All implants achieved
      osteointegration. These results were obtained by accurately managing immediate
      and late post operative period in all of the operated cases. Mean difference for
      height bone loss between the two groups of patients was 2.4mm at T1 and 2.2mm at
      T3. DISCUSSION: The rationale of this split crest flapless modified technique is
      to obtain a proper buccal cortex expansion preserving its vascular supply
      avoiding periosteal elevation for better cortical bone nourishing. Moreover,
      advantages are reported related to the use of PRF. The effectiveness of PRF is
      shown in promoting the healing of surgical wounds, it has, in fact, platelet
      growth factors that can improve the vascularisation of the surgical site,
      promoting neoangiogenesis. Furthermore, by simply changing the settings of the
      centrifuge, it is possible to obtain a normal gelling if it has to be used as
      regenerative and stimulating material, or more consistent substance to be used as
      a filler in the split crest gap. CONCLUSIONS: The main advantages in using the
      platelet-rich fibrin are healing and bone regenerative properties in combination
      with its complete resorption after surgery, thus avoiding a second surgery time,
      important factor in the elderly patients. Currently, it is a minimally invasive
      technique with low risks and satisfactory clinical results such preventing
      complications or implant failure particularly in elderly patients for age related
      conditions.

PMID- 27689518
TI  - A retained foreign body granuloma mimicking a left ventricular psuedoanuerysm.
AB  - INTRODUCTION: Gossypiboma, also referred to as a textiloma, gauzoma or muslinoma
      describe a mass in the body composed of a central cotton core surrounded by a
      foreign body reaction. It has an estimated incidence of 1/1000-1/10000 surgeries,
      occurring in the abdomen (56%), pelvis (18%) and least commonly the thorax (11%)
      and represents an unfortunate event for both the patient and the operating
      surgeon with severe liability implications. PRESENTATION OF CASE: We report a
      case of a 49-year-old male with Marfan Syndrome who was admitted to the
      cardiology department with a four day history of shortness of breath and
      associated dull, non-radiating chest pain. Past history included a previous
      Bentall procedure for a type-A aortic dissection and coronary artery bypass
      grafting involving a saphenous vein graft to the right coronary artery. A
      computed tomography (CT) scan showed a round, heterogeneous mass measuring 14*9cm
      with lobulated contours, situated adjacent to the left ventricle along the left
      posterior region of the aorta. The mass was resected and further dissection
      revealed a plastic band harboured from the core of the mass. DISCUSSION: The
      majority of cases of intrathoracic gossypiboma present as intractable cough or an
      incidental finding on radiological evaluation. Dyspnoea alone is relatively
      underreported as a presenting symptom of this condition CONCLUSION: This case
      highlights the important clinical history features for diagnosing this surgical
      error, including persistent respiratory symptoms and a history of cardio-thoracic
      surgery. It also emphasizes on the need for implementing definite strategies to
      prevent the occurrence of gossypiboma in surgical practice.

PMID- 27689520
TI  - Sigmoid endometriosis in a post-menopausal woman leading to acute large bowel
      obstruction: A case report.
AB  - INTRODUCTION: Endometriosis is usually a disease involving women of reproductive
      age. Colonic endometriosis is a rare sequelae. It usually presents vaguely with
      nonspecific abdominal pain, dyspareunia, fecal tenesmus, rectal bleeding or
      painful defecation. There are very few case reports of sigmoid endometriosis in
      the literature, more so ones involving post-menopausal women. Our report
      highlights such a case, mimicking a malignant rectosigmoid stricture leading to a
      large bowel obstruction. CASE PRESENTATION: A 63year old lady was referred by her
      General Practitioner for further investigation of recent altered bowel habit. She
      underwent an incomplete colonoscopy due to stricturing in the sigmoid. She
      subsequently was admitted with abdominal pain, distension and vomiting, with
      imaging consistent with a large bowel obstruction secondary to a stricturing mass
      within the rectosigmoid which was suspicious for malignancy. An emergency
      laparotomy and Hartmann's procedure was performed. She had an uncomplicated post
      surgical recovery. Histology revealed no underlying malignancy, but confirmed
      colonic endometriosis. CONCLUSION: This case report shows that colonic
      endometriosis, although rare, can be significantly infiltrative and lead to
      complications such as a large bowel obstruction. Diagnosing this condition can be
      challenging and usually requires histological confirmation.

PMID- 27689519
TI  - Gastric GIST or gastric schwannoma-A diagnostic dilemma in a young female.
AB  - INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the commonest mesenchymal
      tumor of GI tract and 60-70% of it seen in the stomach, whereas Gastric
      schwannoma is a benign, slow growing and one of the rare neoplasms of stomach.
      Age distribution, clinical, radiological features and gross appearance of both
      tumors are similar. PRESENTATION OF CASE: We report a rare case of gastric
      schwannoma in a 20-year-old girl, who underwent subtotal gastrectomy with the
      suspicion of a GIST preoperatively but later confirmed to be gastric schwannoma
      postoperatively after immunohistochemical study. DISCUSSION: Accordingly, the
      differential diagnosis for gastric submucosal mass should be gastric schwannoma.
      Furthermore, Gastric schwannoma is a benign neoplasm with excellent prognosis
      after surgical resection, whereas 10-30% of GIST has malignant behavior.
      Therefore, it is important to distinguish between gastric schwannoma and GIST so
      as to make an accurate diagnosis for optimally guide treatment options.
      CONCLUSION: Due to the paucity of gastric schwannoma, the index of suspicion for
      this diagnosis is low. So it is important to include gastric schwannoma in the
      differential diagnosis when preoperative imaging studies reveal submucosal
      exophytic gastric mass and after resection of the tumor with a negative margin,
      it should be sent for immunohistochemical study for confirmation of diagnosis.

PMID- 27689521
TI  - Migration of an intrauterine device to the left inguinal region, the first
      reported case.
AB  - INTRODUCTION: A large number of complications are reported with the use of IUD.
      Migration to inguinal region has not been mentioned in literature. We report a
      rare case of migrated IUD to inguinal canal. CASE REPORT: A 25-year-old lady
      presented with a painfull mass in the left inguinal region. Diagnostic work up
      showed migrated IUD to inguinal region. Operation was done and the impacted IUD
      with surrounding granuloma was retrieved. DISCUSSION: When the string of the IUD
      is no longer visible at the external os of the cervix, radiological scan must be
      performed, this should begin with a sonographic examination and plain abdominal
      radiography may be used to localize the IUD. CONCLUSION: IUD Migration may occur
      to unusual area and perforation can be misdiagnosed as non-witnessed expulsion.

PMID- 27689522
TI  - Angiomyxolipoma of the right sub-brow: Case report with review of the literature.
AB  - INTRODUCTION: Angiomyxolipoma (AML) is a rare variant of benign lipoma with
      characteristic histopathological and immuno-histochemical features. It consists
      of fatty tissue admixed with myxoid stroma and blood vessels. It was first
      described by Mai et al. in 1996 [1], with a total number of 19 cases reported
      since. PRESENTATION: This is the first report of an AML in subcutaneous tissue of
      the face, presenting as a 4-month old cystic lesion in a 78-year old lady.
      Diagnosis was based on radiological and histopathological with cytochemical
      findings. DISCUSSION: It is important to distinguish this lesion as distinct from
      malignant subcutaneous lesions of fatty tissue, especially with short history as
      seen in our case. CONCLUSION: Precise diagnosis of angiomyxolipoma is important
      to avoid unnecessary investigations, stress and misdiagnosis of myxoid
      liposarcoma.

PMID- 27689523
TI  - Thoracoscopic treatment of a broncho-esophageal fistula: A case report.
AB  - INTRODUCTION: Broncho-esophageal fistula is a rare clinical condition which can
      be manifested with non-specific signs and symptoms. PRESENTATION OF A CASE: Here,
      we report an adult case of a broncho-esophageal fistula in a 43-year-old man
      referred for chronic cough after fluid food intake and weight loss. Barium
      swallow, esophagogastroduodenoscopy, bronchoscopy and Computed Tomography of the
      chest demonstrated a broncho-esophageal fistula between the apical segmental
      bronchus of the lower right lobe and the middle section of the esophagus. The
      patient underwent video-assisted thoracoscopic surgery for resection of the
      fistula. No post-operative complications occurred. DISCUSSION: Broncho-esophageal
      fistula in adults is rare and its diagnosis is often delayed due to the frequent
      lack of specific symptoms. Although there is no standard protocol, the most
      widely used treatment is thoracotomy with identification and dissection of the
      fistula tract followed by repair of bronchial and esophageal defects.
      CONCLUSIONS: Video-assisted thoracoscopic surgery appears to be an effective and
      minimally invasive approach for the treatment of broncho-esophageal fistulas,
      especially in young, healthy subjects.

PMID- 27689524
TI  - Primary umbilical endometriosis: A painful swelling in the umbilicus
      concomitantly with menstruation.
AB  - BACKGROUND: Primary umblikal endometriosis is a rare illness. In this report we
      aimed to discuss the management of this rare condition. CASE SUMMARY: A 28-year
      old nulliparous woman was present at our clinic who was suffering from painful
      swelling in the umbilicus during her menstruation for the last 3 months. Her
      examination showed a dark-color sensitive nodule of 20*15mm in size in the
      umbilicus. A lower abdominal tomography was performed to exclude the presence of
      a concomitant pelvic endometriosis, and it showed increased density consistent
      with subcutaneous inflammation in the umbilicus. Her medical history and physical
      examination suggested primary umbilical endometriosis. A total resection
      including umbilicus was performed. DISCUSSION: Primary umbilical endometriosis is
      a rare benign disease and clinically difficult to differentiate from other
      diseases that cause umbilical nodule. Imaging modalities have no pathognomonic
      findings for diagnosis. Surgical exploration and excision are the definitive and
      safe treatment of primary umbilical endometriosis. CONCLUSION: Total umbilical
      resection should be preferred to avoid local recurrent.

PMID- 27689525
TI  - Nonfunctional paraganglioma of the head of the pancreas: A rare case report.
AB  - BACKGROUND: Paragangliomas are rare neoplasms that originate from the neural
      crest. They are malignant in approximately 10% of cases, with a 50% survival rate
      at 5 years from diagnosis. In most cases, manifestations of malignancy (such as
      metastasis) are lacking, and paragangliomas are considered benign lesions.
      Pancreatic paragangliomas are extremely rare, with only 31 cases described in the
      scientific literature to date. CASE SUMMARY: Here we describe a case of a 55-year
      old Caucasian male patient referred to our institution in September 2013 for
      lumbar pain lasting five months. The ultrasound and the CT scan revealed a 2.5cm
      solid nodule located in the uncinate process of the pancreas. On the basis of
      this evidence, the preoperative diagnosis was a pancreatic neuroendocrine tumor
      (NET), which was further confirmed by a subsequent In-Pentetreotide Scan
      examination. A pylorus-preserving duodenocephalopancreasectomy was performed.
      Pancreatic paraganglioma was the final pathological diagnosis. Rare localizations
      of paraganglioma are often discovered casually, during imaging examinations for
      other clinical reasons, as happened in the case of our patient. It appears
      evident that the preoperative diagnosis of pancreatic paragangliomas is extremely
      challenging. Surgery represents the cornerstone of the clinical management of
      these neoplasms, primarily for the need of a definitive diagnosis, which is
      difficult to assess preoperatively in most cases. CONCLUSIONS: Our strategy is
      the same as that adopted for the management of pancreatic NETs; the dimensional
      limit for a conservative resection is 2cm, while major resections (Whipple's
      approach or distal pancreatectomy) should be employed in larger tumors, which are
      generally associated with a worse prognosis.

PMID- 27689526
TI  - Perivascular epithelioid cell tumor of the uterus: Report of two cases and mini
      review of the literature.
AB  - INTRODUCTION: Perivascular Epithelioid Cell tumor (PEComa) is a rare neoplasm of
      mesenchymal origin, with the uterus being the most common site of appearance,
      regarding the female genital tract. CASE REPORT: We present two cases of PEComas
      of the uterus in patients aged 57 and 42-years-old, presented to our department
      with palpable abdominal masses and abnormal vaginal bleeding. During follow up
      period, both patients are free of recurrent disease one and two years after
      surgery, respectively, without receiving any adjuvant treatment. CONCLUSIONS:
      PEComa of the female gynecological tract is a rare entity presenting with
      variable symptoms and different prognosis for each individual case. The diagnosis
      is based on histopathology and immunohistochemistry reports and the optimal
      treatment is the surgical resection of the tumor.

PMID- 27689527
TI  - Successful laparoscopic cholecystectomy for acute cholecystitis with
      kyphoscoliosis by the devised placement of trocar ports: A case report.
AB  - INTRODUCTION: Kyphoscoliosis, which is a deformity of the spine caused by aging
      and osteoporosis, results in various surgical difficulties for laparoscopic
      cholecystectomy (LC) due to low-lying costal arches, such as a small abdominal
      working space, disturbance of the surgical view and decreased controllability of
      the surgical instrument. PRESENTATION OF CASE: We herein report the case of a 92
      year old woman with severe kyphoscoliosis who was diagnosed with Grade II acute
      cholecystitis. Taking her general status into consideration, emergency
      percutaneous transhepatic gallbladder drainage (PTGBD) was initially performed.
      After PTGBD, the patient's physical status and systemic inflammation markedly
      improved. She then underwent interval LC. The surgical view of the upper abdomen
      including the gallbladder was entirely interrupted by bilateral low-lying costal
      arches with adhesion to the greater omentum. To access the gallbladder without
      interruption by the low-lying costal arch, the first umbilical port was changed
      to a multi-port with surgical glove and an additional port was added in the left
      abdomen. Consequently, LC was safely accomplished with the creation of the
      critical view. DISCUSSION: A low-lying costal arch due to kyphoscoliosis can
      prevent surgeons from accessing the gallbladder. LC with the standard 4-port
      method could not be accomplished because of insufficient lifting of the low-lying
      costal arch. Devised placement of the ports is needed to access the gallbladder
      between bilateral low-lying costal arches. CONCLUSION: A transumbilical multi
      port and left abdominal port may be effective for successful LC of acute
      cholecystitis with kyphoscoliosis.

PMID- 27689528
TI  - Multiple hormone deficiency syndrome in heart failure with preserved ejection
      fraction.

PMID- 27689530
TI  - ME-CAGEBIRDr,X-CPMG-HSQMBC. A phase sensitive, multiplicity edited long range
      HSQC with absorptive line shapes.
AB  - ME-CAGEBIRDr,X-CPMG-HSMBC pulse sequence is a phase sensitive, carbon
      multiplicity edited 2D-experiment for detecting heteronuclear correlations
      originating from long-range 1H, 13C-couplings, nJCH. The presented method allows
      measurement of nJCH-values as well as is capable of separating different carbon
      types in subspectra (13C/13CH2 and 13CH/13CH3) with minimal amount of cross talk
      i.e. cross peaks from wrong carbon multiplicity. Pure lineshapes and clean
      subspectra are achieved by utilizing CPMG in polarization transfer period, CRISIS
      approach in multiplicity editing period and zero-quantum filtration. The obtained
      spectral properties together with simple setup of the experiment make ME
      CAGEBIRDr,X-CPMG-HSMBC a useful addition into synthetic organic chemistry
      oriented NMR-tool collection.

PMID- 27689531
TI  - Reaction monitoring using hyperpolarized NMR with scaling of heteronuclear
      couplings by optimal tracking.
AB  - Off-resonance decoupling using the method of Scaling of Heteronuclear Couplings
      by Optimal Tracking (SHOT) enables determination of heteronuclear correlations of
      chemical shifts in single scan NMR spectra. Through modulation of J-coupling
      evolution by shaped radio frequency pulses, off resonance decoupling using SHOT
      pulses causes a user-defined dependence of the observed J-splitting, such as the
      splitting of 13C peaks, on the chemical shift offset of coupled nuclei, such as
      1H. Because a decoupling experiment requires only a single scan, this method is
      suitable for characterizing on-going chemical reactions using hyperpolarization
      by dissolution dynamic nuclear polarization (D-DNP). We demonstrate the
      calculation of [13C, 1H] chemical shift correlations of the carbanionic active
      sites from hyperpolarized styrene polymerized using sodium naphthalene as an
      initiator. While off resonance decoupling by SHOT pulses does not enhance the
      resolution in the same way as a 2D NMR spectrum would, the ability to obtain the
      correlations in single scans makes this method ideal for determination of
      chemical shifts in on-going reactions on the second time scale. In addition, we
      present a novel SHOT pulse that allows to scale J-splittings 50% larger than the
      respective J-coupling constant. This feature can be used to enhance the
      resolution of the indirectly detected chemical shift and reduce peak overlap, as
      demonstrated in a model reaction between p-anisaldehyde and isobutylamine. For
      both pulses, the accuracy is evaluated under changing signal-to-noise ratios
      (SNR) of the peaks from reactants and reaction products, with an overall standard
      deviation of chemical shift differences compared to reference spectra of 0.02ppm
      when measured on a 400MHz NMR spectrometer. Notably, the appearance of decoupling
      side-bands, which scale with peak intensity, appears to be of secondary
      importance.

PMID- 27689529
TI  - Global gene profiling of aging lungs in Atp8b1 mutant mice.
AB  - OBJECTIVE: Recent studies implicate cardiolipin oxidation in several age-related
      diseases. Atp8b1 encoding Type 4 P-type ATPases is a cardiolipin transporter.
      Mutation in Atp8b1 gene or inflammation of the lungs impairs the capacity of
      Atp8b1 to clear cardiolipin from lung fluid. However, the link between Atp8b1
      mutation and age-related gene alteration is unknown. Therefore, we investigated
      how Atp8b1 mutation alters age-related genes. METHODS: We performed Affymetrix
      gene profiling of lungs isolated from young (7-9 wks, n=6) and aged (14 months,
      14 M, n=6) C57BL/6 and Atp8b1 mutant mice. In addition, Ingenuity Pathway
      Analysis (IPA) was performed. Differentially expressed genes were validated by
      quantitative real-time PCR (qRT-PCR). RESULTS: Global transcriptome analysis
      revealed 532 differentially expressed genes in Atp8b1 lungs, 157 differentially
      expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related
      genes in Atp8b1 lungs showed enrichment of Xenobiotic metabolism and Nrf2
      mediated signaling pathways. The increase in Adamts2 and Mmp13 transcripts in
      aged Atp8b1 lungs was validated by qRT-PCR. Similarly, the decrease in Col1a1 and
      increase in Cxcr6 transcripts was confirmed in both Atp8b1 mutant and C57BL/6
      lungs. CONCLUSION: Based on transcriptome profiling, our study indicates that
      Atp8b1 mutant mice may be susceptible to age-related lung diseases.

PMID- 27689532
TI  - Low-power suppression of fast-motion spin 3/2 signals.
AB  - Triple Quantum Filters (TQFs) are frequently used for the selection of bi
      exponentially relaxing spin 3/2 nuclei (in particular 23Na) in ordered
      environments, such as biological tissues. These methods provide an excellent
      selection of slow-motion spins, but their sensitivity is generally low, and
      coherence selection requirements may lead to long experiments when applied in
      vivo. Alternative methods, such as 2P DIM, have demonstrated that the
      sensitivities of the signals from bi-exponentially relaxing sodium can be
      significantly increased using strategies other than TQFs. A shortcoming of the 2P
      DIM method is its strong dependence on B0 inhomogeneities. We describe here a
      method, which is sensitive to the slow-motion regime, while the signal from spins
      in the fast-motion regime is suppressed. This method is shown to be more
      effective than TQFs, requires minimal phase cycling for the suppression of the
      influence of rf inhomogeneity, and has less dependence on resonance offsets and
      B0-inhomogeneity than 2P DIM.

PMID- 27689534
TI  - Is N-acetylcysteine effective in the treatment of pulmonary fibrosis?
AB  - Idiopathic pulmonary fibrosis is a progressive chronic respiratory disease that
      in final stages carries high mortality. Several treatment options have been
      proposed, including N-acetylcysteine, but its role is not clearly established.
      Searching in Epistemonikos database, which is maintained by screening 30
      databases, we identified eight systematic reviews including 16 trials addressing
      the question of this article. We combined the evidence using meta-analysis and
      generated a summary of findings following the GRADE approach. We concluded N
      acetylcysteine might increase the risk of hospitalizations and exacerbations.
      While it is unclear whether this leads to increased mortality because the
      certainty of the evidence is very low, in general there is consensus that it
      should not be used except in the context of a new clinical trial.

PMID- 27689535
TI  - Versatile and Resilient Hydrogen-Bonded Host Frameworks.
AB  - Low-density molecular host frameworks, whether equipped with persistent molecular
      scale pores or virtual pores that are sustainable only when occupied by guest
      molecules, have emerged as a promising class of materials owing to the ability to
      tailor the size, geometry, and chemical character of their free space through the
      versatility of organic synthesis. As such, molecular frameworks are promising
      candidates for storage, separations of commodity and fine chemicals,
      heterogeneous catalysis, and optical and electronic materials. Frameworks
      assembled through hydrogen bonds, though generally not stable toward collapse in
      the absence of guests, promise significant chemical and structural diversity,
      with pores that can be tailored for a wide range of guest molecules. The utility
      of these frameworks, however, depends on the resilience of n-dimensional hydrogen
      bonded motifs that serve as reliable building blocks so that the molecular
      constituents can be manipulated without disruption of the anticipated global
      solid-state architecture. Though many hydrogen-bonded frameworks have been
      reported, few exist that are amenable to systematic modification, thus limiting
      the design of functional materials. This Account reviews discoveries in our
      laboratory during the past decade related to a series of host frameworks based on
      guanidinium cations and interchangeable organosulfonate anions, in which the 3
      fold symmetry and hydrogen-bonding complementarity of these ions prompt the
      formation of a two-dimensional (2-D) quasi-hexagonal hydrogen-bonding network
      that has proven to be remarkably resilient toward the introduction of a wide
      range of organic pendant groups attached to the sulfonate. Since an earlier
      report in this journal that focused primarily on organodisulfonate host
      frameworks with lamellar architectures, this unusually persistent network has
      afforded an unparalleled range of framework architectures and hundreds of new
      crystalline materials with predictable solid-state architectures. These range
      from the surprising discovery of inclusion compounds in organomonosulfonates
      (GMS), as well as organodisulfonates (GDS), structural isomerism reminiscent of
      microstructures observed in soft matter, a retrosynthetic approach to the
      synthesis of polar crystals, separation of molecular isomers, storage of unstable
      molecules, formation of a zeolite-like hydrogen-bonded framework, and
      postsynthetic pathways to inclusion compounds through reversible guest swapping
      in flexible GS frameworks. Collectively, the examples described in this Account
      illustrate the potential for hydrogen-bonded frameworks in the design of
      molecular materials, the prediction of solid-state architecture from simple
      empirical parameters, and the importance of design principles based on robust
      high dimensional networks. These and other emerging hydrogen-bonded frameworks
      promise new advanced materials that capitalize fully on the ability of materials
      chemists to manipulate solid-state structure through molecular design.

PMID- 27689533
TI  - Iodinated benzimidazole PARP radiotracer for evaluating PARP1/2 expression in
      vitro and in vivo.
AB  - BACKGROUND: PARP inhibitors (PARPi) have the potential to impact cancer therapy
      in a selective patient population; however, despite current patient selection
      methods clinical trials have shown mixed response rates. It is therefore
      clinically useful to determine which patients will respond prior to receiving
      PARPi therapy. One essential biomarker is to measure the level of PARP enzyme
      expression in tumors. Small molecule radiotracers have been developed to
      accurately quantify PARP-1 expression in vitro and in vivo. [125I]KX-02-019 is
      the first report of a radioiodinated analogue of the benzimidazole class of
      PARPi. Herein, we studied the pharmacological properties of [125I]KX-02-019 as
      well as the in vivo biodistribution. METHODS: [125I]KX-02-019 was evaluated in
      both cancer and non-cancer cell lines. We evaluated the pharmacologic properties
      of [125I]KX-02-019 in live cells by measuring enzyme association and dissociation
      kinetics, saturation, and specificity. In addition, competitive inhibition
      experiments were carried out with commercially available PARPi. Protein
      expression was analyzed by Western blot to compare PARP-1 and PARP-2 expression
      across cell lines studied. The biodistribution was studied in a mouse EMT6 tumor
      model at time points of 0.5, 1, 2, 4 and 6h. RESULTS: [125I]KX-02-019 showed
      subtle differences in pharmacological properties in the absence of PARP-2. In
      addition, [125I]KX-02-019 was competitively displaced by clinical PARPi. In vivo
      biodistribution studies showed an increasing tumor to muscle ratio over 6h as
      well as fast clearance from healthy tissues. CONCLUSION: [125I]KX-02-019 has
      binding sites in both PARP1 KO cells as well as PARP2 KO cells showing higher
      affinity for PARP-2. This observation is supported by a decrease in binding
      affinity in PARP2 KO cells compared to PARP1 KO cells. The pharmacologic and
      biological properties of [125I]KX-02-019 studied in vitro and in vivo showed that
      this analogue may be useful in determining pharmacokinetic and pharmacodynamic
      properties of clinical PARPi.

PMID- 27689536
TI  - Charge-Carrier Dynamics in 2D Hybrid Metal-Halide Perovskites.
AB  - Hybrid metal-halide perovskites are promising new materials for use in solar
      cells; however, their chemical stability in the presence of moisture remains a
      significant drawback. Quasi two-dimensional (2D) perovskites that incorporate
      hydrophobic organic interlayers offer improved resistance to degradation by
      moisture, currently still at the cost of overall cell efficiency. To elucidate
      the factors affecting the optoelectronic properties of these materials, we have
      investigated the charge transport properties and crystallographic orientation of
      mixed methylammonium (MA)-phenylethylammonium (PEA) lead iodide thin films as a
      function of the MA-to-PEA ratio and, thus, the thickness of the "encapsulated" MA
      lead-halide layers. We find that monomolecular charge-carrier recombination rates
      first decrease with increasing PEA fraction, most likely as a result of trap
      passivation, but then increase significantly as excitonic effects begin to
      dominate for thin confined layers. Bimolecular and Auger recombination rate
      constants are found to be sensitive to changes in electronic confinement, which
      alters the density of states for electronic transitions. We demonstrate that
      effective charge-carrier mobilities remain remarkably high (near 10 cm2V-1s-1)
      for intermediate PEA content and are enhanced for preferential orientation of the
      conducting lead iodide layers along the probing electric field. The trade-off
      between trap reduction, electronic confinement, and layer orientation leads to
      calculated charge-carrier diffusion lengths reaching a maximum of 2.5 MUm for
      intermediate PEA content (50%).

PMID- 27689537
TI  - Enhancement of Energy Storage and Photoresponse Properties of Folic Acid
      Polyaniline Hybrid Hydrogel by in Situ Growth of Ag Nanoparticles.
AB  - Electrically conductive hydrogels are a fascinating class of materials that
      exhibit multifarious applications such as photoresponse, energy storage, etc.,
      and the three-dimensional micro- and nanofibrillar structures of the gels are the
      key to those applications. Herein, we have synthesized a hybrid hydrogel based on
      folic acid (F) and polyaniline (PANI) in which F acts as a supramolecular cross
      linker of PANI chains. The gels are mechanically robust and are characterized by
      field-emission scanning electron microscopy, transmission electron microscopy,
      and spectroscopic, rheological, and universal testing measurements. The hybrid
      xerogel exhibit a BET surface area 238 m2 g-1, conductivity of 0.04 S/cm,
      specific capacitance of 295 F/g at a current density of 1A/g, and photocurrent of
      ~2 mA under white-light illumination. Silver nanoparticles (AgNPs) are in situ
      grown to elegantly improve the conductivity, energy storage, and photoresponse
      capability of the gels. The formation of AgNPs drastically improves the specific
      capacitances up to 646 F/g (at current density 1A/g), excellent rate capability
      (403 F/g at 20 A/g), and stable cycling performance with a retention ratio of 74%
      after 5000 cycles. The AgNPs embedded gel exhibits dramatic enhancement of
      photocurrent to 56 mA, and its time-dependent photoillumination corroborates
      faster rise and decay of current compared to those of folic acid-polyaniline
      hydrogel.

PMID- 27689538
TI  - DPPTE Thiolipid Self-Assembled Monolayer: A Critical Assay.
AB  - Supported lipid membranes represent an elegant way to design a fluid interface
      able to mimic the physicochemical properties of biological membranes, with
      potential biotechnological applications. In this work, a diacyl phospholipid, the
      1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol (DPPTE), functionalized with a
      thiol group, was immobilized on a gold surface. In this molecule, the thiol
      group, responsible for the Au-S bond (45 kJ/mol) is located on the phospholipid
      polar head, letting the hydrophobic chain protrude from the film. This system is
      widely used in the literature but is no less challenging, since its
      characterization is not complete, as several discordant data have been obtained.
      In this work, the film was characterized by cyclic voltammetry blocking
      experiments, to verify the SAM formation, and by reductive desorption
      measurements, to estimate the molecular density of DPPTE on the gold surface.
      This value has been compared to that obtained by quartz crystal microbalance
      measurements. Ellipsometry and impedance spectroscopy measurements have been
      performed to obtain information about the monolayer thickness and capacitance.
      The film morphology was investigated by atomic force microscopy. Finally, Monte
      Carlo simulations were carried out, in order to gain molecular information about
      the morphologies of the DPPTE SAM and compare them to the experimental results.
      We demonstrate that DPPTE molecules, incubated 18 h below the phase transition
      temperature (T = 41.1 +/- 0.4  degrees C) in ethanol solution, are able to form a
      self-assembled monolayer on the gold surface, with domain structures of different
      order, which have never been reported before. Our results make possible
      rationalization of the scattered results so far obtained on this system, giving a
      new insight into the formation of phospholipids SAMs on a gold surface.

PMID- 27689539
TI  - DFT Study of Hydrogen-Bonding Interaction, Solvation Effect, and Electric-Field
      Effect on Raman Spectra of Hydrated Proton.
AB  - Strong hydrogen-bonding interaction and Raman spectra of hydrated proton have
      been investigated using hybrid density functional theory method B3LYP. The
      solvation model of density (SMD) approach is employed in the present calculation
      to simulate hydrated protons in aqueous solution. Focusing on the different
      hydrogen-bonded Eigen-water and Zundel-water interactions, we present a better
      assignment of Raman signals of hydrated proton on the basis of vibrational
      analysis in different environments. Our results showed that B3LYP calculations
      could give a good prediction for characteristic vibrational frequencies of Eigen
      and Zundel isomers in liquid phase. The O-H stretching vibrational frequencies
      from Eigen and Zundel units are very sensitive to hydrogen-bonding interaction
      with solvent water molecules. Moreover, the solvation effect and the external
      electric-field effect lead to the proton deviating from the central position of
      Zundel structure and finally resulting in a transition to Eigen one in aqueous
      solution. Furthermore, by combining theoretical prediction and Raman scattering
      theory, we calculate absolute Raman intensities of characteristic signals based
      on the polarizability tensor derivatives of hydrated proton clusters. This is
      very helpful to infer the microstructure of hydrated protons in aqueous solution
      by using Raman measurements.

PMID- 27689540
TI  - Highly Preorganized Ligand 1,10-Phenanthroline-2,9-dicarboxylic Acid for the
      Selective Recovery of Uranium from Seawater in the Presence of Competing Vanadium
      Species.
AB  - Studies of the complexation of new promising ligands with uranyl (UO22+) and
      other seawater cations can aid the development of more efficient, selective, and
      robust sorbents for the recovery of uranium from seawater. In this work, we
      propose that the ligand design principles based on structural preorganization can
      be successfully applied to obtain a dramatic enhancement in UO22+ ion binding
      affinity and selectivity. This concept is exemplified through the investigation
      of the complexes of UO22+, VO2+, and VO2+ with the highly preorganized ligand
      1,10-phenanthroline-2,9-dicarboxylic acid (PDA) using a combination of
      fluorescence and absorbance techniques, along with density functional theory
      (DFT) calculations. The measured stability constant value, log K1, of 16.5 for
      the UO22+/PDA complex is very high compared to uranyl complexes with other
      dicarboxylic ligands. Moreover, PDA exhibits strong selectivity for uranyl over
      vanadium ions, since the determined stability constant values of the PDA
      complexes of the vanadium ions are quite low (V(IV) log K1 = 7.4, V(V) = 7.3).
      The structures of the corresponding UO22+, VO2+, and VO2+ complexes with PDA were
      identified by systematic DFT calculations and helped to interpret the stronger
      binding affinity for uranium over the vanadium ions. Because of its high chemical
      stability, selectivity, and structural preorganization for UO22+ complexation,
      PDA is a very promising candidate that can be potentially used in the development
      of novel adsorbent materials for the selective extraction of uranium from
      seawater.

PMID- 27689541
TI  - Z-Selective Cross-Metathesis and Homodimerization of 3E-1,3-Dienes: Reaction
      Optimization, Computational Analysis, and Synthetic Applications.
AB  - Olefin metathesis reactions with 3E-1,3-dienes using Z-selective cyclometalated
      ruthenium benzylidene catalysts are described. In particular, a procedure for
      employing 3E-1,3-dienes in Z-selective homodimerization and cross-metathesis with
      terminal alkenes is detailed. The reaction takes advantage of the pronounced
      chemoselectivity of a recently reported ruthenium-based catalyst containing a
      cyclometalated NHC ligand for terminal alkenes in the presence of internal E
      alkenes. A wide array of commonly encountered functional groups can be tolerated,
      and only a small excess (1.5 equiv) of the diene coupling partner is required to
      achieve high yields of the desired internal E,Z-diene cross-metathesis product.
      Computational studies have been performed to elucidate the reaction mechanism.
      The computations are consistent with a diene-first pathway. The reaction can be
      used to quickly assemble structurally complex targets. The power of this cross
      metathesis reaction is demonstrated by the concise syntheses of two insect
      pheromones.

PMID- 27689544
TI  - Access to 6a-Alkyl Aporphines: Synthesis of (+/-)-N-Methylguattescidine.
AB  - (-)-N-Methylguattescidine (3) is an alkaloid recently isolated from Fissistigma
      latifolium and assigned as a rare example of a 6a-alkyl aporphine. Herein, we
      report the synthesis of (+/-)-3 and the des-hydroxyl derivative 4 using our
      previously reported ortho-phenol arylation methodology mediated by the XPhos
      precatalyst as a key synthetic step. In addition, substituents on the aryl halide
      portion of the ortho-phenol arylation substrates significantly influenced the
      formation of an oxidized side product.

PMID- 27689543
TI  - Experimental and theoretical analysis of organic dyes having a double D-pi-A
      configurations for dye-sensitized solar cells.
AB  - Two spiro-like organic dyes linked at the thiophene bridge (KS-11 and KS-12)
      together with the original rod-shaped D-pi-A configuration (C1) were designed,
      synthesized, and characterized based on their electronic structure, and determine
      the photophysical and photovoltaic properties for its application in dye
      sensitized solar cells. Compared to C1, the double D-pi-A spiro-like
      configuration, which consists of two separated light-harvesting moieties, was
      found to be beneficial to photocurrent generation provided that they are
      separated properly to prevent intramolecular exciton annihilation. This was
      observed when KS-11, which is linked at the beta-position of the thiophene moiety
      of D-pi-A, was compared with KS-12, where the two D-pi-A are linked with an
      additional thiophene using a alpha-beta linkage. The results show that KS-12
      produced a 20% and 17% increase in photovoltaic efficiency under simulated AM
      1.5G solar irradiation compared to KS-11 and C1, respectively. This increase in
      photovoltaic performance is credited mostly to the reduction of recombination
      effects and the increase in the density of states at the semiconductor surface
      due to high dye loading and better charge-transfer properties.

PMID- 27689542
TI  - Safe Routes to Play? Pedestrian and Bicyclist Crashes Near Parks in Los Angeles.
AB  - BACKGROUND: Areas near parks may present active travelers with higher risks than
      in other areas due to the confluence of more pedestrians and bicyclists, younger
      travelers, and the potential for increased traffic volumes. These risks may be
      amplified in low-income and minority neighborhoods due to generally higher rates
      of active travel or lack of safety infrastructure. This paper examines active
      travel crashes near parks and builds on existing research around disparities in
      park access and extends research from the Safe Routes to School and Safe Routes
      to Transit movements to parks. METHODS: We utilized the Green Visions Parks
      coverage, encompassing Los Angeles County and several other cities in the LA
      Metropolitan area. We used negative bionomial regression modeling techniques and
      ten years of geolocated pedestrian and bicyclist crash data to assess the number
      of active travel injuries within a quarter mile (~400m) buffer around parks. We
      controlled for differential exposures to active travel using travel survey data
      and Bayesian smoothing models. RESULTS: Of 1,311,736 parties involved in 608,530
      crashes, there were 896,359 injuries and 7317 fatalities. The number of active
      travel crash injuries is higher within a quarter-mile of a park, with a ratio of
      1.52 per 100,000 residents, compared to areas outside that buffer. This higher
      rate near parks is amplified in neighborhoods with high proportions of minority
      and low-income residents. Higher traffic levels are highly predictive of active
      travel crash injuries. CONCLUSIONS: Planners should consider the higher risks of
      active travel near parks and the socioeconomic modification of these risks.
      Additional traffic calming and safety infrastructure may be needed to provide
      safe routes to parks.

PMID- 27689545
TI  - Effect of Chlorine Substitution in Modulating the Relative Importance of Two
      Intermolecular Interactions: The Microwave Spectrum and Molecular Structure of
      (E)-1-Chloro-2-fluoroethylene-HCl.
AB  - Fourier transform microwave rotational spectroscopy is used to determine the
      structure of the gas-phase bimolecular complex formed between (E)-1-chloro-2
      fluoroethylene and hydrogen chloride. Extensively split by nuclear quadrupole
      hyperfine structure and isotopic dilution, the spectrum is first identified via
      weak features observed using a broadband chirped pulse spectrometer in the 5.6
      18.1 GHz range and studied in detail with greater sensitivity and resolution over
      6.0-20.0 GHz with a Balle-Flygare, narrowband instrument. The complex has a
      geometry similar to that of vinyl fluoride-HCl, with HCl binding across the C?C
      double bond, forming a hydrogen bond to the fluorine atom of the haloethylene and
      bending to allow a secondary interaction to develop with the hydrogen atom in the
      cis position. Further consideration of structural details among the complexes of
      hydrogen fluoride and hydrogen chloride with (E)-1-chloro-2-fluoroethylene and
      vinyl fluoride suggests that the addition of a trans Cl atom in vinyl fluoride
      enhances the significance of the secondary interaction while deemphasizing that
      of the hydrogen bond.

PMID- 27689546
TI  - The Water Quality in Rio Highlights the Global Public Health Concern Over
      Untreated Sewage.

PMID- 27689547
TI  - Steroid/Antiviral for the treatment of Bell's palsy: Double blind randomized
      clinical trial.
AB  - BACKGROUND: A large number of patients with Bell's palsy fail to recover facial
      function completely after steroid therapy. Only a few small trials have been
      conducted to test whether outcomes can be improved by the addition of antiviral
      therapy. OBJECTIVE: To evaluate the efficacy of treatment with steroid alone
      versus steroid + antiviral in a group of patients with moderately severe to
      severe acute Bell's palsy. METHODS: Fifty eligible patients out of a total of 65
      with acute onset Bell's palsy were randomized to receive the two treatments.
      Evaluation was performed before starting treatment, after 2 weeks of treatment
      and 3 months after onset, using the House and Brackmann facial nerve grading
      system (HB) and the Sunnybrook grading system.This study was registered with
      ClinicalTrials.gov, number NCT02328079. RESULTS: Both treatments had comparable
      demographics and clinical scores at baseline. There was greater improvement in
      the mean HB and Sunnybrook scores of the steroid + antiviral group in comparison
      to steroid group at 3 months. At the end of the 3rd month, 17 patients (68%) had
      good recovery and 8 patients (32%) had poor recovery in the steroid group
      compared with 23 patients (92%) and 2 (8%) respectively in the steroid and
      antiviral group (p = 0.034). CONCLUSION: The combination of steroid and antiviral
      treatment increases the possibility of recovery in moderately severe to complete
      acute Bell's palsy.

PMID- 27689548
TI  - Mental chronometry and mental rotation abilities in stroke patients with
      different degrees of sensory deficit.
AB  - BACKGROUND: Motor imagery is used for treatment of motor deficits after stroke.
      Clinical observations suggested that motor imagery abilities might be reduced in
      patients with severe sensory deficits. This study investigated the influence of
      somatosensory deficits on temporal (mental chronometry, MC) and spatial aspects
      of motor imagery abilities. METHODS: Stroke patients (n = 70; <6 months after
      stroke) were subdivided into 3 groups according to their somatosensory functions.
      Group 1 (n = 31) had no sensory deficits, group 2 (n = 27) had a mild to moderate
      sensory impairment and group 3 (n = 12) had severe sensory deficits. Patients and
      a healthy age-matched control group (n = 23) participated in a mental chronometry
      task (Box and Block Test, BBT) and a mental rotation task (Hand Identification
      Test, HIT). MC abilities were expressed as a ratio (motor execution time-motor
      imagery time/motor execution time). RESULTS: MC for the affected hand was
      significantly impaired in group 3 in comparison to stroke patients of group 1 (p
      = 0.006), group 2 (p = 0.005) and healthy controls (p < 0.001). For the non
      affected hand MC was similar across all groups. Stroke patients had a slower BBT
      motor execution than healthy controls (p < 0.001), and group 1 executed the task
      faster than group 3 (p = 0.002). The percentage of correct responses in the HIT
      was similar for all groups. CONCLUSION: Severe sensory deficits impair mental
      chronometry abilities but have no impact on mental rotation abilities. Future
      studies should explore whether the presence of severe sensory deficits in stroke
      patients reduces the benefit from motor imagery therapy.

PMID- 27689549
TI  - The effects of combined repetitive transcranial magnetic stimulation and
      transcranial direct current stimulation on motor function in patients with
      stroke.
AB  - BACKGROUND: Both transcranial magnetic stimulation (rTMS) and transcranial direct
      current stimulation (tDCS), when provided to stroke patients in combination with
      motor training, enhance therapeutic efficacy and motor function. However, the
      majority of previous studies have only examined a single treatment modality.
      OBJECTIVE: The authors investigated the modulating influence of combination dual
      mode brain stimulation upon bihemispheric stimulation with motor training in
      stroke patients. METHODS: Twenty stroke patients with hemiparesis underwent five
      randomly arranged sessions of diverse combinations of rTMS and tDCS. We applied
      cathodal or anodal tDCS over the contralesional primary motor cortex (cM1) and 10
      Hz rTMS over the ipsilesional primary motor cortex (iM1) in a simultaneous or
      preconditioning method including sham stimulation. Immediately after dual-mode
      stimulation, sequential hand motor training was performed for 5 minutes. The
      total pulses of rTMS and the duration of tDCS and motor training were the same
      for all sessions. Cortical excitability and sequential motor performance were
      evaluated before and after each session. RESULTS: Motor function and corticomotor
      excitability following simultaneous stimulation via cathodal tDCS over the cM1
      combined with 10 Hz rTMS over the iM1 were significantly increased after the
      intervention, with significantly greater motor improvement than seen with other
      treatment conditions (P < 0.05). CONCLUSION: For the combination of bihemispheric
      rTMS and tDCS, simultaneous stimulation of cathodal tDCS and 10 Hz rTMS results
      in better motor performance in stroke patients than other combination methods.
      This result seemed to be related to effective modulation of interhemispheric
      imbalance of cortical excitability by dual-mode stimulation.

PMID- 27689550
TI  - Association between genetic variation in the dopamine system and motor recovery
      after stroke.
AB  - BACKGROUND: The dopamine system plays a key role in motor learning and
      neuroplasticity. Several studies have studied the efficacy of dopaminergic drugs
      in enhancing motor recovery after stroke, but the effects are controversial.
      Although genetic variations in plasticity-related genes influence each
      individual's capacity for recovery after stroke, limited studies have
      investigated the effects of polymorphism of dopamine-related genes. OBJECTIVE: We
      aimed to investigate the association between motor recovery in stroke patients
      and polymorphisms in the dopamine-related genes catechol-O-methyltransferase
      (COMT), dopamine receptor D1 (DRD1), DRD2, and DRD3. METHODS: We enrolled 74
      patients with first-ever stroke (42 males, 32 females, mean age: 61.4+/-14.1 y).
      During admission, blood samples were collected, and the genotypes of COMT, DRD1,
      DRD2, and DRD3 were analyzed. The primary outcome was assessed with Fugl-Meyer
      Assessment (FMA) at 1 week, 3 months, and 6 months after stroke; secondary
      outcomes were assessed with Functional Independence Measure (FIM) and mini-mental
      state examination at 3 and 6 months after stroke. The association between
      polymorphisms and functional outcome was analyzed. RESULTS: There were no
      significant associations between COMT polymorphisms and FMA or FIM scores at 1
      week after stroke or between DRD1, DRD2, or DRD3 genotypes and FMA or FIM scores
      at any point. COMT genotypes were significantly associated with FMA and FIM at 3
      months (p < 0.01 and p < 0.05, respectively) and at 6 months (p < 0.01 and p <
      0.05, respectively). CONCLUSION: These data suggest that genetic variation of
      dopamine-related genes may affect motor recovery after stroke and that COMT
      polymorphism could be useful for predicting motor recovery.

PMID- 27689551
TI  - Effects of anodal tDCS and occupational therapy on fine motor skill deficits in
      patients with chronic stroke.
AB  - BACKGROUND: A growing body of evidence supports the effectiveness of using
      transcranial direct current stimulation (tDCS) in patients with chronic hand
      motor impairment resulting from stroke. OBJECTIVE: In this study, we investigate
      and compare the combined effects of anodal tDCS and occupational therapy (OT) to
      sham stimulation with OT (control) on fine motor skill deficits of chronic stroke
      patients. METHODS: A total of 26 stroke patients (at >= 9 months) were randomly
      assigned to an active treatment or a control group in a double-blinded, sham
      controlled, parallel design study. Each group received OT for 45 min/day (10
      sessions for 2 weeks). Treatment was preceded by either 20 minutes of 2 mA anodal
      tDCS over ipsilesional M1 or sham tDCS. A modified Jebsen-Taylor Hand Function
      Test (mJTHFT) was administered as primary outcome measure, and handgrip
      dynamometer and upper limb Fugl-Meyer (ULFM) assessments were performed as
      secondary outcomes. The assessment was done at baseline (T0), after the
      interventions on day 1(T1), day 10 (T2) and day 40 (T3). RESULTS: We observed a
      statistically significant effect in the tDCS group when the results were compared
      to the sham group. The mJTHFT times were significantly shorter immediately after
      treatment and at day 40. The intervention had no effect on handgrip strength or
      ULFM score. CONCLUSION: Fine motor skill deficits in chronic stroke survivors can
      be improved when intensive OT is primed with anodal tDCS over the ipsilesional
      hemisphere.

PMID- 27689552
TI  - An education management information system with simultaneous monitoring of stress
      stimulators for students Mental Health management.
AB  - Education Management Information System (EMIS) is a widely acceptable and
      developing technology within the Information Technology field. The advancement in
      technology in this century is being collaborated with scientific invention or
      explorer and information strengthening or development. This paper presents the
      results and experiences gained from applying students oriented EMIS for
      monitoring and managing mental health. The Mental Health of students depends on
      the acquiring adequate knowledge on basic concepts within a time period or
      academic schedule. It's obviously significance to evaluate and appraise the
      stress stimulators as a challenge or threat. The theoretical framework for the
      study was designed for analyzing the stress stimulators, academic performance and
      EMIS accessibility. The sample examined in this study was stratified random
      sample from 75 students specifically all engineering college in Dindigul District
      of Tamilnadu. The primary factor is the academic stress stimulators that form one
      module of EMIS for each of the key variable such as curriculum & instruction
      related stressors, placement related, teamwork related and assessment related.
      The Mental Health related stress stimulators namely curriculum & syllabus,
      placement related, assessment related and team work related have a significant
      influence on academic performance by students in various institution. The
      important factor leading to the EMIS application in monitoring stress stimulators
      is curriculum & syllabus related and assessment related.

PMID- 27689553
TI  - Personalized reminiscence therapy M-health application for patients living with
      dementia: Innovating using open source code repository.
AB  - Dementia is known to be an illness which brings forth marked disability amongst
      the elderly individuals. At times, patients living with dementia do also
      experience non-cognitive symptoms, and these symptoms include that of
      hallucinations, delusional beliefs as well as emotional liability, sexualized
      behaviours and aggression. According to the National Institute of Clinical
      Excellence (NICE) guidelines, non-pharmacological techniques are typically the
      first-line option prior to the consideration of adjuvant pharmacological options.
      Reminiscence and music therapy are thus viable options. Lazar et al. [3]
      previously performed a systematic review with regards to the utilization of
      technology to delivery reminiscence based therapy to individuals who are living
      with dementia and has highlighted that technology does have benefits in the
      delivery of reminiscence therapy. However, to date, there has been a paucity of M
      health innovations in this area. In addition, most of the current innovations are
      not personalized for each of the person living with Dementia. Prior research has
      highlighted the utility for open source repository in bioinformatics study. The
      authors hoped to explain how they managed to tap upon and make use of open source
      repository in the development of a personalized M-health reminiscence therapy
      innovation for patients living with dementia. The availability of open source
      code repository has changed the way healthcare professionals and developers
      develop smartphone applications today. Conventionally, a long iterative process
      is needed in the development of native application, mainly because of the need
      for native programming and coding, especially so if the application needs to have
      interactive features or features that could be personalized. Such repository
      enables the rapid and cost effective development of application. Moreover,
      developers are also able to further innovate, as less time is spend in the
      iterative process.

PMID- 27689554
TI  - Modeling the virus-immune system interactions in the peripheral bloodstream of
      HIV infected individuals using a cellular automata model with considering the
      effects of antiretroviral therapy.
AB  - BACKGROUND: According to the World Health Organization, by the end of last year,
      about 37 million people throughout the world were diagnosed with AIDS and
      millions of people die each year from this disease. OBJECTIVE: To develop an
      appropriate model which depicts the mechanism of the dynamics involved in the
      interactions between HIV and immune system in peripheral bloodstream of HIV
      infected individuals by considering the phenomena of virus mutation and taking
      into account the role of latently infected cells in speared of infection and
      considering the effects of antiretroviral drugs and occurrence of drug resistance
      in our model in order to assess the results obtained from applying different
      therapeutic methods. METHODS: Two-dimensional CA model with Moor neighboring was
      developed. Various agents which they were referring to peripheral bloodstream
      particles of HIV infected individuals were defined. Then the biological rules
      were extracted from both expert knowledge and the authoritative articles. The
      extracted rules were applied for updating the states of these agents. The effects
      of using antiretroviral drug treatment were considered by applying drug's
      effectiveness of both of protease and reverse transcriptase inhibitors as two
      separate inputs of model. RESULTS: Time evolution curves of concentrations of
      defined agents were shown as our results. In case of considering no treatment,
      our results showed that concentrations of healthy CD4+T cells reached the
      threshold of AIDS after a bout 250 weeks. By applying monotherapy method, the
      concentrations of these cells remained on the threshold of AIDS for a long time
      and applying combined antiretroviral therapy (cART) method leaded to increase the
      concentration of these cells 20% upper than threshold of AIDS. Also, by applying
      monotherapy and cART compared with no treatment, the concentrations of infected
      CD4+T cells 10% and 40% decreased further, respectively and for the level of
      viral load, leads to a reduction of almost 55% and 90%, respectively. Belated
      treatment, comparison with early treatment, caused almost 10% reduce (increase)
      in steady state concentrations of healthy (infected) cells.

PMID- 27689555
TI  - Forecasting behavior in smart homes based on sleep and wake patterns.
AB  - BACKGROUND: The goal of this research is to use smart home technology to assist
      people who are recovering from injuries or coping with disabilities to live
      independently. OBJECTIVE: We introduce an algorithm to model and forecast wake
      and sleep behaviors that are exhibited by the participant. Furthermore, we
      propose that sleep behavior is impacted by and can be modeled from wake behavior,
      and vice versa. METHODS: This paper describes the Behavior Forecasting (BF)
      algorithm. BF consists of 1) defining numeric values that reflect sleep and wake
      behavior, 2) forecasting wake and sleep values from past behavior, 3) analyzing
      the effect of wake behavior on sleep and vice versa, and 4) improving prediction
      performance by using both wake and sleep scores. RESULTS: The BF method was
      evaluated with data collected from 20 smart homes. We found that regardless of
      the forecasting method utilized, wake behavior and sleep behavior can be modeled
      with a minimum accuracy of 84%. Additionally, normalizing the wake and sleep
      scores drastically improves the accuracy to 99%. CONCLUSIONS: The results show
      that we can effectively model wake and sleep behaviors in a smart environment.
      Furthermore, wake behaviors can be predicted from sleep behaviors and vice versa.

PMID- 27689556
TI  - Muscle synergy extraction during arm reaching movements at different speeds.
AB  - OBJECTIVE: Muscle synergy is the activation of a group of muscles that contribute
      to a particular movement. The goal of the present study is to examine the
      hypothesis that human reaching movements at different speeds share similar muscle
      synergies and to investigate the kinesiology basis and innervation of muscles.
      METHODS: Electromyographic activity from six muscles of the upper limb and
      shoulder girdle were recorded during three movements at different speeds, i.e.
      slow, moderate and fast. The effect of window length on the RMS signal of the EMG
      was analyzed and then EMG envelope signals were decomposed using non-negative
      matrix factorization. For each of the ten subjects, three synergies were
      extracted which accounted for at least 99% of the VAF. For each movement, the
      muscle synergies and muscle activation coefficients of all participants were
      clustered in to three partitions. Investigation showed a high similarity and
      dependency of cluster members due to the cosine similarity and mutual information
      in muscle synergy clustering. For further verification, the EMG envelope signals
      for all subjects were reconstructed. RESULTS: The results indicated a lower
      reconstruction error using the center of the muscle synergy clusters in
      comparison with the average of the activation coefficients, which confirms the
      current research's hypothesis.

PMID- 27689557
TI  - Increased rate of bacterial colonization on PE-components in total joint
      arthroplasty: An evaluation through sonication.
AB  - BACKGROUND: It is currently unclear if an isolated exchange of the mobile
      components, in cases of periprosthetic joint infection (PJI), leads to a complete
      eradication of all bacteria or if residual bacteria remain attached to the
      retained components? OBJECTIVE: The purpose of this study was to investigate if
      bacteria only adhere to certain components or materials, or if they are
      ubiquitously distributed throughout the joint. METHODS: Twenty hundred and eighty
      four patients undergoing revision total hip or total knee arthroplasty surgery
      were included in this retrospective cohort study. Synovial fluid cultures,
      periprosthetic tissue cultures, histological samples and sonicate fluid cultures
      (SFC) from the individual endoprosthetic components were acquired. The isolated
      bacterial species were recorded according to their endoprosthetic component of
      origin. RESULTS: In 72% of all cases with multiple SFC, the cultures were
      concordant with all samples being either homogenously negative or showing
      positive bacterial growth. The polyethylene (PE) components showed a
      significantly higher rate of bacterial isolation than the non-mobile components.
      All components and materials showed bacterial colonization, however between all
      other components or materials were not statistically significant. CONCLUSIONS: PE
      components show a higher rate of bacterial isolation than other components. If an
      isolated bearing exchange is performed this should be supplemented by adequate
      antimicrobial therapy.

PMID- 27689558
TI  - Recommendations for measuring non-image-forming effects of light: A practical
      method to apply on cognitive impaired and unaffected participants.
AB  - BACKGROUND: The non-image-forming effects of luminous radiation on people with
      intellectual disabilities or dementia received attention from researchers. Such
      studies, however, have generally been conducted using disparate methodologies
      which precludes generalization and reproducibility. OBJECTIVE: The aim of this
      study was to determine the practical applicability of measurement devices for
      studies investigating non-image-forming effects of luminous radiation,
      specifically for people with intellectual disabilities or dementia. METHODS: In
      three experiments, ten cognitive impaired people and thirty-nine unaffected
      subjects participated by wearing one or more portable devices. Six devices were
      assessed in total. Measurement data was accompanied with user experiences
      obtained from questionnaires, interviews and observations in order to assess the
      devices on practical and comfort issues. RESULTS: On average, the devices worn by
      the cognitive impaired subjects were not experienced as annoying or irritating.
      No significant differences are found between genders and for one of the portable
      devices significantly less annoyance was reported by the cognitive impaired
      participants compared to the unaffected group of participants. INNOVATIVE
      SOLUTION: The three phases of the research process in towards measuring personal
      luminous exposures are: selection of the most suitable portable device,
      application of the assessment method, and the application of the device in the
      (pilot) study. CONCLUSIONS: However, the findings of this study suggest that
      inaccuracies potentially caused by practical and comfort issues associated with
      the portable devices need to be considered.

PMID- 27689559
TI  - Development of a mobile application for oral cancer screening.
AB  - PURPOSE: To develop a mobile application (app) for oral cancer screening.
      METHODS: The app was developed using Android system version 4.4.2, with JAVA
      language. Information concerning sociodemographic data and risk factors for oral
      cancer development, e.g., tobacco and alcohol use, sun exposure and other
      contributing factors, such as unprotected oral sex, oral pain and denture use,
      were included. We surveyed a population at high risk for oral cancer development
      and then evaluated the sensitivity/specificity/accuracy and predictive values of
      clinical oral diagnosis between two blinded trained examiners, who used movies
      and data from the app, and in loco oral examination as gold-standard. RESULTS: A
      total of 55 individuals at high risk for oral cancer development were surveyed.
      Of these, 31% presented homogeneous/heterogeneous white lesions with potential of
      malignancy. The clinical diagnoses performed by the two examiners using videos
      were found to have sensitivity of 82%-100% (average 91%), specificity of 81%-100%
      (average 90.5%), and accuracy of 87.27%-95.54% (average 90.90%), as compared with
      the gold-standard. The Kappa agreement value between the gold-standard and the
      examiner with the best agreement was 0.597. CONCLUSION: Mobile apps including
      videos and data collection interfaces could be an interesting alternative in oral
      cancer research development.

PMID- 27689560
TI  - Moodle: The cost effective solution for internet cognitive behavioral therapy (I
      CBT) interventions.

PMID- 27689561
TI  - Angiojet rheolytic thrombectomy combined with catheter fragmentation in a patient
      presenting with massive pulmonary embolism and cardiogenic shock.
AB  - Massive pulmonary embolism (MPE) is associated with a high rate of mortality, and
      chronic thromboembolic pulmonary hypertension leads to ongoing morbidity among
      many survivors. Here we report a case of a MPE successfully treated by Angiojet
      rheolytic thrombectomy combined with catheter fragmentation. This is the first
      report of the use of these two methods together for MPE treatment.

PMID- 27689562
TI  - Cybersecurity in healthcare: A systematic review of modern threats and trends.
AB  - BACKGROUND: The adoption of healthcare technology is arduous, and it requires
      planning and implementation time. Healthcare organizations are vulnerable to
      modern trends and threats because it has not kept up with threats. OBJECTIVE: The
      objective of this systematic review is to identify cybersecurity trends,
      including ransomware, and identify possible solutions by querying academic
      literature. METHODS: The reviewers conducted three separate searches through the
      CINAHL and PubMed (MEDLINE) and the Nursing and Allied Health Source via ProQuest
      databases. Using key words with Boolean operators, database filters, and hand
      screening, we identified 31 articles that met the objective of the review.
      RESULTS: The analysis of 31 articles showed the healthcare industry lags behind
      in security. Like other industries, healthcare should clearly define
      cybersecurity duties, establish clear procedures for upgrading software and
      handling a data breach, use VLANs and deauthentication and cloud-based computing,
      and to train their users not to open suspicious code. CONCLUSIONS: The healthcare
      industry is a prime target for medical information theft as it lags behind other
      leading industries in securing vital data. It is imperative that time and funding
      is invested in maintaining and ensuring the protection of healthcare technology
      and the confidentially of patient information from unauthorized access.

PMID- 27689563
TI  - Relative lower body circumferences are associated with the prevalence of
      metabolic syndrome and arterial stiffness.
AB  - Body circumference is a known health-related factor. This cross-sectional study
      aimed to investigate the associations of relative lower body circumferences with
      metabolic syndrome (MetS) and arterial stiffness (AS) in 684 men aged > 40 (mean,
      54.6 +/- 8.5) years. Participants were measured for waist, thigh, and calf
      circumferences; underwent blood tests and blood pressure measurements to detect
      MetS; and received brachial ankle pulse wave velocity measurements to measure AS.
      The waist-to-thigh, waist-to-calf, and thigh-to-calf circumferences were
      calculated and classified into quartiles. Age-adjusted multiple logistic
      regression models were used to assess the associations between the circumference
      ratios and AS vs. non-AS and MetS vs. non-MetS (systolic and diastolic blood
      pressure, triglycerides, high-density lipoprotein cholesterol, and fasting plasma
      glucose). The mean body mass index was 24.9 +/- 2.8 kg/m2; the mean waist, thigh,
      and calf circumferences were 87.4 +/- 7.6, 53.8 +/- 4.2, and 36.4 +/- 2.7 cm,
      respectively. Compared to the lowest quartiles, participants in waist-to-thigh
      circumference quartiles 3 (odds ratio [OR] = 3.195, 95% confidence interval [CI]
      = 1.825-5.594, p < 0.001) and 4 (OR = 4.755, 95% CI = 2.715-8.325, p < 0.001),
      and participants in waist-to-calf circumference quartiles 2 (OR = 2.511, 95% CI =
      1.397-4.511, p = 0.002), 3 (OR = 3.929, 95% CI = 2.076-7.435, p < 0.001), and 4
      (OR = 5.298, 95% CI = 2.847-9.858, p < 0.001) had significantly greater risks of
      MetS; participants in waist-to-calf circumference quartile 4 (OR = 2.481, 95% CI
      = 1.477-4.167, p < 0.001) and participants in waist-to-calf circumference
      quartile 4 (OR = 1.763, 95% CI = 1.088-2.856, p = 0.021) had a significantly
      greater risk of AS, indicating that age-adjusted relative lower body
      circumferences associate with MetS and AS. Large thigh and calf circumferences
      may indicate reduced risks for cardiovascular disease.

PMID- 27689564
TI  - A new approach for speech synthesis in cochlear implant systems based on
      electrophysiological factors.
AB  - BACKGROUND: Speech synthesis models have been considered as viable tools for
      performance evaluation of cochlear stimulation algorithms, due to the
      difficulties of clinical tests. OBJECTIVE: The present study has developed a tool
      that can be used before any audio signal reconstruction algorithm, which shows
      more conformity with the electrophysiological parameters of the patient in
      evaluation of the cochlear implant stimulation algorithms. METHODS: In this
      method, excitable nerve fiber characteristics such as stimulation threshold and
      effective refractory period have been considered in the signal pre-reconstruction
      process. This algorithm subsumes the user's biological parameters (e.g., the
      manner of distribution of the remaining intact nerve fibers) as well as the
      stimulation signal parameters (e.g., stimulation rate, pulse width, amplitude of
      stimulation, the distance between stimulation electrode and fibers) in the signal
      pre-reconstruction. RESULTS: Effect of changes in these parameters can be
      observed by the number of excited fibers, which is directly related to the signal
      intensity and pitch frequency perceived by the user. The obtained results from
      simulations are in accordance with previous clinical findings. Also, the ability
      of the proposed tool can be seen by the correspondence between the results
      obtained from the proposed model and the amplitude growth functions of the
      cochlear implant users. CONCLUSIONS: This paper has introduced a tool for signal
      reconstruction from electrical stimulation so that a more comprehensive criterion
      for examination of the stimulating algorithms in cochlear implant can be
      achieved.

PMID- 27689565
TI  - Comparison of knee characteristics between professional and amateur golfers
      during the downswing.
AB  - Evaluating the biomechanical and performance factors of the knee joint during
      golf swing can provide objective and quantitative information about improving the
      performance and development of efficient physical training, as the legs are
      important for achieving an efficient swing and maximum speed of the club head in
      golf. In the present study, kinematic movements of the knee joint were identified
      during the downswing by using 3-dimensional motion analysis, and isokinetic
      strength was measured with driver and 5-iron clubs in 15 professional (PRO)
      golfers and 10 amateur (AMA) golfers. Results showed that PRO golfers had a
      narrower minimal angle between the thigh and lower leg in the trail knee than the
      AMA golfers, regardless of the club used, and the angular velocity of the lead
      knee was faster during the downswing with a 5-iron club in the AMA golfers than
      in the PRO golfers. The PRO and AMA golfers had a wider minimal angle between the
      thigh and lower leg, smaller total range of movement, and slower angular velocity
      of the trail knee when swinging a 5-iron club than when swinging a driver club.
      These results are expected to provide useful information to prevent golf-related
      injuries that usually arise in the knee joint and help improve the golf
      performance of amateur golfers.

PMID- 27689566
TI  - Comparison of distribution of lung aeration measured with EIT and CT in
      spontaneously breathing, awake patients1.
AB  - BACKGROUND: Both Electrical Impedance Tomography (EIT) and Computed Tomography
      (CT) allow the estimation of the lung area. We compared two algorithms for the
      detection of the lung area per quadrant from the EIT images with the lung areas
      derived from the CT images. METHODS: 39 outpatients who were scheduled for an
      elective CT scan of the thorax were included in the study. For each patient we
      recorded EIT images immediately before the CT scan. The lung area per quadrant
      was estimated from both CT and EIT data using two different algorithms for the
      EIT data. RESULTS: Data showed considerable variation during spontaneous
      breathing of the patients. Overall correlation between EIT and CT was poor (0.58
      0.77), the correlation between the two EIT algorithms was better (0.90-0.92).
      Bland-Altmann analysis revealed absence of bias, but wide limits of agreement.
      CONCLUSIONS: Lung area estimation from CT and EIT differs significantly, most
      probably because of the fundamental difference in image generation.

PMID- 27689567
TI  - Effect of crosslinking methods on the structure and biocompatibility of polyvinyl
      alcohol/gelatin cryogels.
AB  - In this study, polyvinyl alcohol (PVA) and gelatin based cryogels were prepared
      by crosslinking chemically or physically for tissue engineering applications.
      Different PVA/Gelatin ratios (100:0, 90:10, 70:30, 50:50) and crosslinking
      methods have been used to prepare cryogels; chemical and physical structure of
      the prepared matrices were analysed by FTIR and SEM; swelling and degradation
      profiles were followed. Chemical and physical crosslinking was obtained by using
      glutaraldehyde as crosslinker and by applying freeze thawing cycle, respectively.
      Gelatin concentration and crosslinking method had significant effect on the pore
      size, swelling ratio and degradation profiles of the cryogels. Biocompatibility
      of the cryogels were also investigated by MTT assay. SEM was used to investigate
      the cell morphology on the scaffolds. The MTT assay findings prove that
      physically crosslinked PVA/Gelatin scaffolds are more biocompatible and enhance
      more the adhesion and proliferation of mouse embryonic fibroblast cells (MEF)
      than chemically crosslinked PVA/Gelatin scaffolds. The overall results
      demonstrated that, the PVA/Gelatin cyrogels as a suitable biomaterial for tissue
      engineering applications and crosslinking methods affect the architecture and
      characteristic properties of the cryogels.

PMID- 27689568
TI  - A study of the effect of clinical washing decontamination process on corrosion
      resistance of Martensitic Stainless Steel 420.
AB  - Corrosion of surgical instruments provides a seat for contamination and prevents
      proper sterilisation, placing both patients and medical staff at risk of
      infection. Corrosion can also compromise the structural integrity of instruments
      and lead to mechanical failure in use. It is essential to understand the various
      factors affecting corrosion resistance of surgical instruments and how it can be
      minimised.This paper investigates the effect on corrosion resistance from the
      clinical washing decontamination (WD) process, specifically by studying the
      changes in surface roughness and Cr/Fe ratio. Results indicate that the WD
      process provides a positive effect on smooth polished samples, while a lesser
      positive effect was observed on rough reflection reduced samples.

PMID- 27689569
TI  - Hemostyptic property of chitosan: Opportunities and pitfalls.
AB  - BACKGROUND: Chitosan is used in a wide field of applications and therapies and
      has been reported to be an effective hemostyptic. The objective of this study was
      to provide further information about the use of chitosan as a hemostyptic agent
      also taking into focus its hemocompatible effects. METHODS: Human whole blood
      (n=5) was anticoagulated with heparin, treated with different chitosan
      concentrations (0, 2.5, 5, 7.5, 10, 12.5, 25 mg/mL) and incubated at 37 degrees C
      for 30 minutes. Before and after incubation different parameters for coagulation
      and hemocompatibility were evaluated. RESULTS: Blood treated with high chitosan
      concentrations showed enhanced coagulation, which we evaluated with activated
      clotting time, activated partial thromboplastin time and concentration of
      thrombin-antithrombin complexes. Furthermore, we observed an activation of blood
      platelets, complement cascade and granulocytes in the groups treated with
      chitosan. CONCLUSION: Our data indicate that chitosan activates human blood
      coagulation and hence has good properties as a hemostyptic agent. However,
      inflammatory parameters were upregulated after direct contact with human blood
      indicating that systemic administration of chitosans should not be performed
      whereas the topical use of chitosan as a hemostypticum should not present any
      hazard with regard to adverse inflammatory reactions at the site of application.

PMID- 27689570
TI  - Influence of tooth brushing on adhesion strength of orthodontic brackets bonded
      to porcelain.
AB  - BACKGROUND: Adhesive resin composite, which is used to bond orthodontic bracket
      to tooth surface is exposed to the influence of wear by tooth brushing and wear
      may influence loosening of the bracket. OBJECTIVE: The aim of this study was to
      evaluate in vitro the effect of tooth brushing on the adhesion strength of
      orthodontic brackets bonded to surface treated porcelain. METHOD: A total of 90
      glazed porcelain fused to metal facets (PFM) were randomly assigned into 3 groups
      according to the surface treatment to be received. Group 1 was conditioned with
      hydrofluoric acid (HF), group 2 conditioned with grit-blasting (GB) and group 3
      conditioned with tribochemical silica coating (RC). The groups were evaluated for
      surface roughness (Ra) before and after surface treatment. Next, 15 samples from
      each group were subjected to brushing and remaining 15 samples served as the
      baseline (n=15). Adhesion strength (shear bond strength)was recorded using a
      universal testing machine. Data collected were analyzed by ANOVA and Tukey's
      multiple comparison post hoc analysis. RESULTS: Tooth brushing decreased the bond
      strength in all groups. The highest adhesion strength (baseline and after
      brushing) was observed in group 3 (26.8 +/- 1.77 MPa and 23.57 +/- 1.02 MPa) and
      the lowest was found in group 1 (9.6 +/- 1.5 MPa and 5.87 +/- 0.77 MPa). Group 3
      specimens exhibited the highest Ra (1.24 +/- 0.08). CONCLUSION: It was found that
      tooth brushing of the exposed adhesive resin composite at the bracket-bonding
      substrate interface lowers the bonding strength regardless of the surface
      treatment of the substrate.

PMID- 27689571
TI  - Orthodontic tunnel miniscrews with and without TiO2 nanotube arrays as a drug
      delivery system: In vivo study.
AB  - Orthodontic tunnel miniscrews with and without TiO2 nanotube arrays were
      fabricated to improve the induction of new bone formation and osseointegration.
      To inject the drug of recombinant human bone morphogenetic protein, tunnels in a
      conventional machined miniscrew were machined by a computer-numerical-control
      lathe. TiO2 nanotube arrays to load the drug were also formed on the surface of
      the tunnel miniscrew by anodic oxidation. To obtain clean TiO2 nanotube arrays,
      two-step anodic oxidation was conducted. The diameters of TiO2 nanotube window
      and TiO2 nanotube were ~70 nm and ~110 nm, respectively. Three groups, i.e., a
      conventional machined miniscrew, a tunnel miniscrew without TiO2 nanotube arrays,
      and a tunnel miniscrew with TiO2 nanotube arrays, were prepared and inserted in
      the legs of five New Zealand White rabbits. In a histomorphometric analysis, the
      bone implant contact ratios of the tunnel miniscrews with the TiO2 nanotube
      arrays and without the TiO2 nanotube arrays were 5.84% and 5.88%, respectively.
      These values were higher than the value of 4.30% for the conventional machined
      miniscrew. The bone surface ratios in the tunnel miniscrew with and without the
      TiO2 nanotube were also higher than those of the conventional machined miniscrew.
      The measured values of the tunnel miniscrew with and without the nanotube and the
      conventional miniscrew were 76.75%, 73.41%, and 44.82%, respectively, although
      the differences were statistically insignificant. New bone at three weeks and six
      weeks after the operations were found in the tunnel miniscrews in fluorescent
      images. Both the tunnel miniscrews with and without the TiO2 nanotube arrays
      demonstrated greater bone formation compared to the conventional miniscrews.
      However, TiO2 nanotube arrays was not likely to provide additional benefit to the
      tunnel miniscrew. An in vivo study suggested that the tunnel fabricated in the
      miniscrew can be efficient drug-delivery systems to improve osseointegration.

PMID- 27689572
TI  - Interfragmentary motion assessment for three different fixation techniques of
      femoral neck fractures in young adults.
AB  - BACKGROUND: Vertical femoral neck fractures in the youth could be happened in
      high-energy accidents, and because of dominant shearing forces, this fracture is
      considered as a troublesome injury with a controversy regarding selection of the
      best fixation method. OBJECTIVE: The long term goal of this quasi-experimental
      study was to find the more stable fixation method among cannulated screws (CSs),
      proximal femoral locking plate (PFLP), and dynamic hip screw with derotational
      screw (DHS+DS) for this kind of fracture. METHODS: Twelve fresh-frozen cadaveric
      femurs were assigned to three groups that were matched for mean bone mineral
      density and stiffness of intact bone. Vertical fractures were artificially
      mimicked in the specimens and fixed using three different implants, i.e. CSs,
      PFLP, and DHS+DS. Then, the samples were tested under incremental, cyclic, and
      failure loading phases. RESULTS: The differences in all biomechanical parameters
      were statistically significant among tested groups (p<0.05). All biomechanical
      parameters for the DHS+DS method of fixation are significantly different from
      those corresponding to CSs (p<0.05). There were no significant differences in
      failure load and failure energy between the PFLP and CSs techniques (p>0.05).
      Also, there were no significant differences in relative stiffness and femoral
      head displacement between the PFLP and DHS+DS groups (p>0.05). CONCLUSIONS: Based
      on the clinical assumption that restricted weight-bearing regimen is recommended
      in the postoperative rehabilitation protocol, the results of this study suggest
      that the priority order of selection for the stable fixation implant of vertical
      femoral neck fracture in young patients is DHS+DS, then PFLP, and finally CSs.

PMID- 27689573
TI  - Differences in bead-milling-induced hemolysis of red blood cells due to shape and
      size of oscillating bead.
AB  - BACKGROUND: Red blood cell (RBC) susceptibility to hemolysis - or fragility - can
      be profiled by subjecting a sample to progressive durations of mechanical stress
      and measuring hemolysis upon each. The ability to control stress application with
      multiple variable parameters can be useful in various areas of research. Bead
      milling, by oscillating an object in a blood sample, can offer control of
      parameters including oscillation force and frequency. OBJECTIVE: This work
      addresses the role of bead shape and size, for a given container, in potentially
      creating qualitatively as well as quantitatively different fluidic stresses in
      the sample. METHODS: Identical, diluted RBC samples were stressed via bead
      milling using different beads, with other parameters the same. Resulting
      hemolysis was plotted for several time increments in each case. RESULTS: For a
      cylindrical bead oscillating at a given frequency and force, bead length was a
      determinant of albumin's protective effect on RBC, as reflected by mechanical
      fragility. Compared to a sphere of same diameter, the protective effect was
      absent with shorter cylinders, whereas for longer ones it appeared enhanced.
      CONCLUSIONS: Bead milling based RBC fragility testing could present a useful tool
      for creating, and studying effects of different shear stress types in inducing
      hemolysis.

PMID- 27689574
TI  - Effect of the surface morphology of silk fibroin scaffolds for bone regeneration.
AB  - Existing scaffolds cannot adequately satisfy the simultaneous requirements for
      the regeneration of bone. The challenge remains of how to improve the integration
      of newly formed bone with the surrounding tissues. The purpose of this study was
      to investigate the effects of two silk fibroin scaffolds, a hexafluoro
      isopropanol-based silk fibroin (HFIP-F) and an aqueous-based silk fibroin (A-F),
      for their osteoinductive potentials in large critical size bone defects in vivo.
      beta-tricalcium phosphate (beta-TCP) was used as a positive control. After
      implantation into defects created in the knee joints of rabbits for 1 and 2
      weeks, hematoxylin and eosin (H-E) and Azan staining revealed that the A-F
      scaffold as well as beta-TCP had stronger osteoinductive ability than the HFIP-F
      scaffold. The A-F scaffold exhibited prominent areas of neo-tissue containing
      bone-like nodules. Furthermore, induced osteointegration was observed between
      native and neo-tissue within the osteo defects in the knee joints of rabbits.
      Immunohistochemical staining showed the highest expression of Runx2, BMP-2, BMP
      7, Smad1/5/9 and Phospho-Smad in the A-F scaffold implants. Osteoinduction of the
      porous A-F scaffold might be influenced by the amount of BMP signaling present in
      the local microenvironment in the implants. This study opens a new avenue to use
      A-F silk fibroin scaffolds for the regeneration of bone defects.

PMID- 27689575
TI  - Compression properties and dissolution of bioactive glass S53P4 and n-butyl-2
      cyanoacrylate tissue adhesive-composite.
AB  - Bioactive glass (BG)-containing fiber-reinforced composite implants, typically
      screw-retained, have started to be used clinically. In this study, we tested the
      mechanical strength of composites formed by a potential implant adhesive of n
      butyl-2-cyanoacrylate glue and BG S53P4 particles. Water immersion for 3, 10 or
      30 days had no adverse effect on the compression strength. When cyanoacrylate
      glue-BG-composites were subjected to simulated body fluid immersion, the average
      pH rose to 7.52 (SD 0.066) from the original value of 7.35 after 7 days, and this
      pH increment was smaller compared to BG particle-group or fibrin glue-BG
      composite group. Based on these results n-butyl-2 cyanoacrylate glue, by
      potentially producing a strong adhesion, might be considered a possible
      alternative for fixation of BG S53P4 containing composite implants. However, the
      mechanical and solubility properties of the cyanoacrylate glue may not encourage
      the use of this tissue adhesive with BG particles.

PMID- 27689576
TI  - The demands and benefits of ergonomics in Sri Lankan apparel industry: A case
      study at MAS holdings.
AB  - BACKGROUND: Apparel exports bring in sizeable foreign income to Sri Lanka. To
      protect and promote this industry is a paramount need. This can be carried out by
      applying Human Factors/Ergonomics (HFE) which has proved to control negative
      effects at work places. OBJECTIVES: This paper reports a case study which
      describes the demands and benefits of HFE in MAS Holdings which owns a large
      share of the apparel industry in Sri Lanka. METHODS: The study consisted of walk
      through observation survey, a questionnaire survey and ergonomic work place
      analysis followed by a training programme to selected employees in three
      companies. RESULTS: Positive responses to questionnaires revealed good ergonomic
      practices in the work places surveyed. Ergonomically unfit chairs and potential
      hazards e.g. exposure to noise and hot environment were detected. It is seen that
      MAS have introduced strategies originated by Toyota Production System viz. 5S,
      Kaizen, six sigma etc., which are in fact ergonomic methods. A progressive
      project MAS boast of viz. 'MAS Operating System' (MOS) empowers training and
      development to employees. CONCLUSIONS: MAS Holdings has adequately realized the
      benefits of applying HFE as evident by the number of awards received. Relevant
      companies were advised to take appropriate corrective measures to control the
      potential hazards.

PMID- 27689577
TI  - Tool development to assess the work related neck and upper limb musculoskeletal
      disorders among female garment workers in Sri-Lanka.
AB  - BACKGROUND: Musculoskeletal disorders (MSDs) have been identified as a
      predisposing factor for lesser productivity, but no validated tool has been
      developed to assess them in the Sri- Lankan context. OBJECTIVE: To develop a
      validated tool to assess the neck and upper limb MSDs. METHODS: It comprises
      three components: item selections, item reduction using principal component
      analysis, and validation. A tentative self-administrated questionnaire was
      developed, translated, and pre-tested. Four important domains - neck, shoulder,
      elbow and wrist - were identified through principal component analysis. RESULTS:
      Prevalence of any MSDs was 38.1% and prevalence of neck, shoulder, elbow and
      wrist MSDs are 12.85%, 13.71%, 12%, 13.71% respectively. Content and criterion
      validity of the tool was assessed. Separate ROC curves were produced and
      sensitivity and specificity of neck (83.1%, 71.7%), shoulder (97.6%, 91.9%),
      elbow (98.2%, 87.2%), and wrist (97.6%, 94.9%) was determined. Cronbach's Alpha
      and correlation coefficient was above 0.7. CONCLUSION: The tool has high
      sensitivity, specificity, internal consistency, and test re-test reliability.

PMID- 27689578
TI  - Improving performance and happiness among healthcare workers through a body-mind
      approach in a healthcare setting in Sri Lanka.
AB  - BACKGROUND: Cognitive ergonomics in the work place has become a serious concern
      with the need to keep people happy at work while maintaining high productivity.
      Hence, it is worth exploring how the outcomes of lifestyle-based mind development
      programs can bring about happiness in workplace while keeping productivity and
      quality of services high. OBJECTIVE: The objective of the present work was to
      test a body-mind technique to improve cognitive ergonomics in a health care work
      setting. METHODS: Principal investigator explored many body-mind techniques
      before selecting the present method of "insight meditation" which he mastered
      before applying it on a group of scholars who made it a part of their lifestyle.
      Later it was introduced to a sample of 500 volunteer health personnel in the
      western province to generate a ripple effect of happiness at work. RESULTS:
      Initial qualitative information indicated improvement of some aspects of
      cognitive ergonomics among those who practiced it. There was a relief from stress
      during the practice sessions and improvements in the commitment to work and in
      team spirit. A demand was observed for further training. A quasi-experimental
      study to test the improvements is underway. CONCLUSIONS: Health workers showed
      interest in the mind training and potential benefits to individuals and the
      institutions were observed.

PMID- 27689579
TI  - Knowledge, attitudes and practices regarding handling mercury containing medical
      devices among nurses in a tertiary care paediatric hospital in Sri Lanka.
AB  - BACKGROUND: Mercury is a highly toxic heavy metal used in many medical devices in
      the healthcare sector, making nurses one of the vulnerable occupational groups.
      OBJECTIVE: To assess knowledge, attitudes and practices regarding handling
      mercury containing devices and factors associated with knowledge among nurses in
      a paediatric hospital in Sri Lanka. METHODS: A descriptive cross-sectional study
      was conducted among nurses (n = 538) working in Lady Ridgeway Hospital, Sri
      Lanka. Information on the use of mercury containing medical devices, accidental
      exposure, management of spillage and disposal was gathered using a self
      administered questionnaire. RESULTS: A total of 472 nurses responded with a
      response rate of 87.7%. Of the 347 mercury thermometer users, 67.1% had
      experienced breakages while among 405 mercury sphygmomanometer users, 20.0% had
      experienced mercury spillages, during a three months period prior to the study. A
      majority (56.8%) had 'good' overall knowledge regarding mercury and its adverse
      effects while 94.1% had favorable attitudes towards protecting themselves/others
      from mercury. Practices related to managing a mercury spill were poor. Work
      experience >10 years (p = 0.032) and favorable attitude (p = 0.007) were
      associated with good knowledge while having a training on managing a mercury
      spillage was not (p = 0.850). CONCLUSIONS: Gaps in practices on managing a
      mercury spillage were evident. Current training programmes were not found to be
      effective.

PMID- 27689580
TI  - Occupational health issues in small-scale industries in Sri Lanka: An
      underreported burden.
AB  - BACKGROUND: Work-related diseases and occupational accidents affect a significant
      number of workers globally. The majority of these diseases and accidents are
      reported from developing countries; and a large percentage of the workforce in
      developing countries is estimated to be employed in small-scale industries. Sri
      Lanka is no exception. These workers are exposed to occupational hazards and are
      at a great risk of developing work- related diseases and injuries. OBJECTIVE: To
      identify occupational health issues faced by small-scale industry workers in Sri
      Lanka. METHODS: A cross sectional study was conducted among workers in four
      selected small-scale industry categories in two districts of Sri Lanka. A small
      scale industry was defined as a work setting with less than 20 workers. Cluster
      sampling using probability proportionate to size of workers was used. Eighty
      clusters with a cluster size of eight from each district were selected. Data was
      collected using a pre-tested interviewer administered questionnaire. RESULTS: Our
      study surveyed 198 industries. Headache (2.2%, 95% CI 1.5-3.1) and eye problems
      (2.1%, 95% CI 1.4-2.9) were the commonest general health issues detected. Back
      pain (4.8%, 95% CI 3.8-6.1) was the most prevalent work-related musculoskeletal
      pain reported. Knee pain was the second highest (4.4%, 95% CI 3.4-5.6). Most of
      the work-related musculoskeletal pain was either of short duration or long
      lasting. CONCLUSIONS: Work-related musculoskeletal pain was much more common than
      the general health issues reported. Health promotional programs at workplaces
      focusing ergonomics will benefit the workers at small-scale industries inSri
      Lanka.

PMID- 27689581
TI  - Burden of lupus on work: Issues in the employment of individuals with lupus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) or Lupus is one of the leading
      causes of work disability in the United States, accounting for about 20% of the
      more than estimated 1.5 million Americans with a work disability. The symptoms of
      lupus can have a profound impact on the person's employment. Impacts of lupus are
      more pronounced among young and middle-adulthood. Studies have shown that loss in
      work hours cost the nation nearly $13 billion annually. The loss also impacts the
      individual's work, quality of life, self-management, and self-efficacy.
      OBJECTIVE: In this article, the author describes the financial burden of lupus.
      The article also describes the substantial impact of lupus on employment outcomes
      for individuals living with the condition. The author also reviews major signs
      and symptoms of disease and their impact on employment. RESULTS: Findings from
      this research can be used to identify various accommodations and strategies for
      individuals to prevent flare-ups. CONCLUSIONS: The paper presents innovative
      strategies that include early interventions and how employers andco-workers can
      provide helpful support that includes job accommodations to individuals with
      lupus.

PMID- 27689582
TI  - Methods of 3D data applications to inform design decisions for physical comfort.
AB  - BACKGROUND: Past research on anthropometry, especially in the industry of
      external ear worn products, stresses that positive comfort is enhanced when there
      is sufficient knowledge of human factors; however, most anthropometric studies
      focus only on the acquirement and presentation of data. OBJECTIVE: The aim of
      this paper is to provide with different methods to support design applications of
      3-dimensional head and ear data with a focus on external ear products. METHODS:
      Two hundred persons representing the Danish population were scanned. The 3D data
      was collected, refined and analysed in 3 meaningful ways: Advanced geometry,
      visualisations of data and for the generation of archetypes. RESULTS: A matrix
      containing 29 new ear dimensions was generated. The application of methods led to
      the development of 9 additional dimensions. The paper finally presents all phases
      of the analysis of the 3D data in the form of a methodological framework.
      CONCLUSIONS: The paper contributes with, in addition to the methodological
      framework, techniques to extract data based on product understanding and how the
      data can be used to define archetypes for focus groups and other qualitative
      assessments. In their endeavour to develop successful and comfortable products
      designers should focus more on fitting the task into the human by benchmarking
      human dimensions against product data.

PMID- 27689583
TI  - Integrating ergonomics knowledge into business-driven design projects: The
      shaping of resource constraints in engineering consultancy.
AB  - BACKGROUND: The integration of ergonomics knowledge into engineering projects
      leads to both healthier and more efficient workplaces. There is a lack of
      knowledge about integrating ergonomic knowledge into the design practice in
      engineering consultancies. OBJECTIVES: This study explores how organizational
      resources can pose constraints for the integration of ergonomics knowledge into
      engineering design projects in a business-driven setting, and how ergonomists
      cope with these resource constraints. PARTICIPANTS: An exploratory case study in
      an engineering consultancy was conducted. A total of 27 participants were
      interviewed. METHODS: Data were collected applying semi-structured interviews,
      observations, and documentary studies. Interviews were transcribed, coded, and
      categorized into themes. RESULTS: From the analysis five overall themes emerged
      as major constituents of resource constraints: 1) maximizing project revenue, 2)
      payment for ergonomics services, 3) value of ergonomic services, 4) role of the
      client, and 5) coping strategies to overcome resource constraints. CONCLUSION: We
      hypothesize that resource constraints were shaped due to sub-optimization of
      costs in design projects. The economical contribution of ergonomics measures was
      not evaluated in the entire life cycle of a designed workplace. Coping strategies
      included teaming up with engineering designers in the sales process or creating
      an alliance with ergonomists in the client organization.

PMID- 27689584
TI  - Ergonomic workplace assessment in orthotic and prosthetic workshops.
AB  - BACKGROUND: In Iranian orthotic and prosthetic workshops, the majority of
      activities are carried out by manpower and the tasks are labor-intensive. In
      these workshops, ergonomic aspects of working conditions are seldom considered.
      OBJECTIVE: This study was conducted in orthotic and prosthetic workshops with the
      objectives of determination of prevalence rate of MSDs among employees and
      assessment of ergonomics working conditions. METHODS: In this cross-sectional
      study, all employees (n = 42; 29 males and 13 females) in 11 active orthotic and
      prosthetic production centers of Shiraz city participated. Data were collected
      using Nordic Musculoskeletal disorders Questionnaire (NMQ) and observational
      technique by an ergonomics checklist for assessment of working conditions.
      RESULTS: The means (SD) of age and job tenure (years) in the study individuals
      were 37.26 (10.21) and 12.8 (9.39), respectively. The most prevalent MSD symptoms
      in the past 12 months were reported in the lower back (42.9%), shoulders (40.5%)
      and knees (40.5%). Working conditions assessment showed that the main ergonomic
      problems in the workshops studied originated from awkward working posture,
      improper workstation design, poorly designed hand tools and incorrect manual
      material handling. CONCLUSION: Any interventional program for working conditions
      improvement should, therefore, focus on these areas.

PMID- 27689585
TI  - From the Editor.

PMID- 27689586
TI  - The effectiveness of rehabilitation on pain-free farming in agriculture workers
      with low back pain in India.
AB  - BACKGROUND: Studies have shown that farming is associated with many agricultural
      workers experiencing low back pain (LBP). The rehabilitation of these workers
      should facilitate their functioning, activities and level of participation in an
      adequate way. OBJECTIVE: The objectives of this study were to identify the health
      components associated with LBP and to evaluate the effectiveness of the
      interventions in returning agricultural workers with LBP to their vocation using
      the International Classification of Function (ICF) -based tools. METHODS: Thirty
      one full time agricultural workers from 3 different Indian states were
      prospectively assessed using the ICF core set for LBP. ICF core sets permitted
      analysis of limitations of function from both the participant and rehabilitation
      team's perspectives. Each ICF category was rated using an ICF qualifier. The
      components identified were linked to the ICF categorical profile and assessment
      sheet. The clinicians identified the global, service program and cycle goals
      based on ICF. The participants' functioning was followed over a 4-month period.
      RESULTS: After intervention, the participants were able to undergo their routine
      activities without increases in pain. However, on returning to active farming,
      participants noted few improvements in the components d410 (changing basic body
      position), d415 (maintaining body position), d430 (lifting and carrying objects),
      d465 (moving around using equipment), d850 (remunerative employment) and d859
      (work and employment, other specified and unspecified). CONCLUSION: The results
      of the study conclude that the current interventions for LBP are not effective in
      returning agriculture workers with LBP in India to pain-free farming. There is an
      urgent need to individualize the health needs of agriculture workers.

PMID- 27689587
TI  - Insufficient time for leisure and perceived health and stress in working parents
      with small children.
AB  - BACKGROUND: More knowledge about how recovery may promote health among parents
      with small children is needed. OBJECTIVE: To explore whether insufficient time
      for leisure was associated with poorer perceived health and higher stress in
      working parents. A further aim was to explore potential gender differences in the
      association between insufficient time for leisure and poor perceived health.
      METHODS: A postal survey including the perceived stress scale and three measures
      of subjective health - self-rated health (SF-36), work-related fatigue (Swedish
      occupational fatigue questionnaire), and Lund subjective health complaints - as
      well as questions about time for leisure was completed by 965 women and 597 men.
      Risk ratios for poor perceived health and stress were estimated using Poisson
      regression, in which also gender interaction was analysed. RESULTS: The results
      showed higher risk for perceived stress among parents reporting insufficient time
      for relaxation, and more subjective health complaints among those reporting
      insufficient time to spend with their children. Overall, effects were larger
      among women than among men. CONCLUSION: A good balance between work and leisure
      seems to be of importance for working parents' perceived health and stress.

PMID- 27689588
TI  - The role of psychosocial and physical work-related factors on the health-related
      quality of life of Iranian industrial workers.
AB  - BACKGROUND: The role of psychosocial and physical work factors in predicting
      health related quality of life (HRQOL) has not been investigated among Iranian
      industrial workers. OBJECTIVE: The present study is designed to assess these
      relationships among Iranian workers from steel and cosmetic factories. METHODS: A
      cross-sectional study was conducted among 280 workers from two factories.
      Psychosocial and physical work factors and HRQOL were measured by the Persian
      translations of the following questionnaires: Job Content Questionnaire (JCQ) and
      the World Health Organization Quality of Life-Brief (WHOQOL-Brief). An instrument
      was developed to assess socio-demographic, health, and other work-related
      factors. The data were analyzed using independent t-tests, Pearson product moment
      correlation and hierarchical multiple regression. RESULTS: Results revealed that
      the respondents generally had poor HRQOLs especially in the environmental domain.
      The steel factory workers who were exposed to higher levels of occupational risk
      factors suffered from poorer HRQOL compared to the cosmetic factory workers. The
      results of hierarchical regression for all participants revealed that social
      support, sleep quality, work schedule, smoking and exercise were significant
      predictors of all domains of HRQOL. CONCLUSIONS: To improve the worker's HRQOL,
      intervention programs should focus on promoting social support, sleep quality,
      exercise and smoking habits. Moreover, reducing hazardous work environments
      should be considered an important intervention to promote HRQOL.

PMID- 27689589
TI  - Stuck in the middle: The emotional labours of case managers in the personal
      injury compensation system.
AB  - BACKGROUND: Case managers within injury compensation systems are confronted with
      various emotional demands. OBJECTIVE: Employing the concept of emotional labour,
      this paper explores distinctive aspects of these demands. METHODS: The findings
      are drawn from focus groups with 21 Australian case managers. RESULTS: Case
      managers work was characterised by extra-role commitments, emotional control,
      stress and balancing tensions arising from differing stakeholder expectations
      about outcomes related to compensation and return to work. CONCLUSIONS: By
      examining the experiences of case managers, the findings add to the literature on
      the emotional labour of front line service workers, especially with respect to
      the demands involved in managing the conflicting demands of work.

PMID- 27689590
TI  - Interventions to reduce injuries among older workers in agriculture: A review of
      evaluated intervention projects.
AB  - BACKGROUND: The number of older workers is increasing throughout the
      industrialised world and older workers are known to be more frequent in the
      injury-prone agricultural sector. OBJECTIVE: This paper sought to extend
      knowledge by reviewing evaluated intervention studies intended to decrease risks
      and work injuries among older workers in agriculture. METHODS: A systematic
      literature review regarding: evaluated intervention projects on injury
      prevention, including participants aged 55 years and older, and working in
      agriculture. RESULTS: This review identified evaluated intervention projects
      regarding: i) intervention in injury prevention; ii) interventions to increase
      knowledge in health and safety tasks and practice; and iii) interventions to
      increase the use of safety equipment in work. The evaluations reviewed showed
      that the interventions were less successful in involving older agricultural
      workers than their younger counterparts. The evaluations also showed that the
      outcome of interventions was generally less positive or brought about no
      significant difference in risk awareness and behaviour change among older
      agricultural workers. CONCLUSIONS: Many articles and statistics describe injuries
      in agriculture. Especially older farm workers are one of the groups with most
      work injuries and deaths. Despite this, an important finding in this review was
      shortage of implemented and evaluated intervention studies orientated toward
      reduce injuries among older workers in agriculture. This review also found that
      no intervention project in the evaluations studied had a clear positive effect.
      Many intervention studies have problems with or lack of evaluation in the study
      design. Based on the results in this review, important future research tasks are
      to improve the design of interventions, devise implementation methods and
      formulate appropriate evaluation methods to measure the outcome of the
      interventions. Intervention programmes also need to involve older workers
      specific physical and cognitive age aspects in the design to increases their
      willingness to participate and to be successful to reduce injuries.

PMID- 27689591
TI  - Elucidating the relationship between work attention performance and emotions
      arising from listening to music.
AB  - BACKGROUND: In addition to demonstrating that human emotions improve work
      attention performance, numerous studies have also established that music alters
      human emotions. Given the pervasiveness of background music in the workplace,
      exactly how work attention, emotions and music listening are related is of
      priority concern in human resource management. OBJECTIVES: This preliminary study
      investigates the relationship between work attention performance and emotions
      arising from listening to music. PARTICIPANTS: Thirty one males and 34 females,
      ranging from 20-24 years old, participated in this study following written
      informed consent. METHODS: A randomized controlled trial (RCT) was performed in
      this study, which consisted of six steps and the use of the standard attention
      test and emotion questionnaire. RESULTS: Background music with lyrics adversely
      impacts attention performance more than that without lyrics. Analysis results
      also indicate that listeners self-reported feeling "loved" while music played
      that implied a higher score on their work-attention performance. Moreover, a
      greater ability of music to make listeners feel sad implied a lower score on
      their work-attention performance. CONCLUSIONS: Results of this preliminary study
      demonstrate that background music in the workplace should focus mainly on
      creating an environment in which listeners feel loved or taken care and avoiding
      music that causes individuals to feel stressed or sad. We recommend that future
      research increase the number of research participants to enhance the
      applicability and replicability of these findings.

PMID- 27689592
TI  - Health promotion in the trucking setting: Understanding Dutch truck drivers' road
      to healthy lifestyle changes.
AB  - BACKGROUND: The working environment, the nature of the work, and the
      characteristics of truck drivers as a social group typically pose great
      challenges for the truck drivers' health and health promotion activities aiming
      to improve it. OBJECTIVE: The purpose was to obtain a better understanding of (a)
      Dutch truck drivers' perceptions of health and lifestyle themes, and (b) the
      challenges they experience in their pursuit of a more healthy lifestyle, as a
      guiding framework for the development of health interventions targeting this
      occupational group. METHODS: In this qualitative study, we conducted and analyzed
      20 semi-structured interviews and seven cases of participant observations with
      Dutch truck drivers. Grounded theory was used to analyze the data. RESULTS: Our
      findings illustrate that Dutch truck drivers wish to improve their lifestyle but
      have unproductive associations with concepts of healthy living as well as a
      tendency to downplay their health risks. In addition, they experience barriers
      within their work and personal environment that prevent them from translating
      their intentions into actual lifestyle changes. CONCLUSIONS: Based on the
      insights derived from the interviews, we discuss recommendations for the
      development of more effective health promotion interventions for truck drivers.

PMID- 27689593
TI  - Uprising: An examination of sit-stand workstations, mental health and work
      ability in sedentary office workers, in Western Australia.
AB  - BACKGROUND: Office-based staff spend around three quarters of their work day
      sitting. People who sit for long periods while at work are at greater risk of
      adverse health outcomes. OBJECTIVE: The pilot study aimed to determine the effect
      of sit-stand workstations on office-based staff sedentary and physical activity
      behaviors, work ability and self-reported physical and mental health outcomes.
      METHODS: A two-group pre-post study design assessed changes in sedentary and
      physical activity behaviors (time spent sitting, standing and stepping and sit
      stand transitions and number of steps taken) work ability and physical and mental
      health. Physical activity behaviors were measured using activPAL activity
      monitors and self-reported data on work ability and physical and mental health
      were collected using an online questionnaire. RESULTS: Relative to the controls
      (n=19), the intervention group (n=18) significantly decreased time spent sitting
      by 100 minutes (p<0.001) and increased standing time by 99 minutes (p<0.001).
      There was a decrease in self-reported current work ability when compared to
      lifetime best (p=0.008). There were no significant differences for all other
      sedentary behavior, other workability outcomes, physical health or mental health
      outcomes at follow-up. CONCLUSIONS: The Uprising Study found that sit-stand
      workstations are an effective strategy to reduce occupational sitting time in
      office-based workers over a one month period.

PMID- 27689594
TI  - Small opportunities are often the beginning of great enterprises: The role of
      work engagement in support of people through the recovery process and in
      preventing relapse in drug and alcohol abuse.
AB  - BACKGROUND: This study, carried out in five Therapeutic Communities (TCs), aims
      to evaluate the relationship between social support and sense of community for
      people with pathological addictions and the personal and professional dimensions
      of hope, resilience, work engagement, future time perspective, and job
      performance. Support to the person is attained through social support at work by
      the supervisor and the person's sense of belonging to the community. OBJECTIVE:
      The purpose of this article is to analyze the relationship between social
      support, sense of community, hope, resilience, work engagement, future time
      perspective, and job performance. METHODS: In order to verify the relations
      between those variables, structural equation models with observed variables (path
      analysis) were estimated using LISREL 8.80. RESULTS: The results show a direct
      relationship between social support at work by the supervisor and hope, as well
      as between sense of community and resilience at work, while work engagement plays
      a mediating role between the two antecedents and the personal and professional
      variables investigated - hope, resilience, future time perspective and
      performance at work. Performance was measured through both people's self
      perceptions and their supervisors' evaluations. A positive correlation exists
      between the two assessments. CONCLUSIONS: The positive consequences of the
      research entail both theoretical and practical aspects.

PMID- 27689595
TI  - Australian fly-in, fly-out operations: Impacts on communities, safety, workers
      and their families.
AB  - BACKGROUND: Australia's mineral, resource and infrastructure sectors continues to
      expand as operations in rural and remote locations increasingly rely on fly-in,
      fly-out or drive-in, drive-out workforces in order to become economically
      competitive. The issues in effectively managing these workforces are becoming
      more apparent with reported high amounts of turnover and concerns for safety and
      performance. The issues presented include a range of physical, mental,
      psychosocial, safety and community challenges. OBJECTIVES: This review aims to
      consolidate a range of research conducted to communicate potential challenges for
      industry in relation to a wide variety of issues when engaging and using
      FIFO/DIDO workforces which includes compressed working schedule design (work
      schedules), working hours, fatigue, safety performance, employee wellbeing,
      turnover, psychosocial relationships and community concerns. METHODS: A
      comprehensive literature review was performed using EBSCOhost, PubMed and google
      scholar, with a focus on FIFO or DIDO workforces engaged within the resources
      sector. Search terms were kept broad in order to capture all national and
      international research conducted and included: "fly-in, fly-out" "FIFO" "DIDO"
      "drive-in, drive-out" "mining". There was no date restriction included in the
      search. RESULTS: Many of the studies were focused on sleep quality, fatigue and
      the influence of lowered safety performance while at work, presenting an
      increased risk for health and safety. These issues may be exacerbated for the
      FIFO workforce when linked to additional research surrounding the extended
      periods of absence from families influencing workers personal relationships,
      psychological wellbeing, job satisfaction and the reported high amounts of
      turnover within the industry. Taken together, this presents a unique implication
      for the management and continued use of FIFO workforces when considering
      balancing safety and performance with economic viability of production and
      operations. CONCLUSIONS: The issues of long working hours, fatigue, turnover and
      job satisfaction are not new to the management of workers. However, FIFO
      workforces appear to be at an increased risk physically and mentally due to a
      culmination of other influences, such as extended and frequent periods of absence
      from friends and families which contribute to feelings of isolation and lowered
      psychological wellbeing. FIFO workers and their families, engage in a unique
      lifestyle, rarely are other workers subjected to long hours and compressed work
      weeks while separated or isolated from their families for extended periods of
      time. Recently, FIFO interest has shifted to understanding the influences on
      employee engagement, satisfaction, retention and safety. Considering the
      management of FIFO workforces from a holistic perspective incorporating all of
      the issues impacting on these workers may assist to ensure the challenges
      associated with FIFO employment are understood, addressed and communicated to
      workers and their families is crucial for safety and health.

PMID- 27689596
TI  - Health promotion in workplaces as a strategy for modification of risk factors for
      Non Communicable Diseases (NCDs): A practical example from Sri Lanka.
AB  - BACKGROUND: Non communicable diseases (NCDs) are emerging as a major public
      health concern worldwide and became a leading cause of mortality in Sri Lanka
      accounting for 65% of deaths. Health promotion strategies aimed at lifestyle
      modification are helpful in modifying risk factors for NCDs. OBJECTIVES: To
      transform a workplace to a health promotion setting where lifestyle changes in
      workers lead to a modification of risk factors for NCDs. METHODS: A health
      promotion program was conducted in a divisional administrative office, in Sri
      Lanka. An office health promotion committee was established and an action plan
      was prepared with participation of the workers. An interviewer administrated
      questionnaire was used to assess risk factors for NCDs. Workers were then
      screened for NCDs. Behavioral change and communication (BCC) programs were
      conducted to improve physical activity and dietary modifications. RESULTS:
      Workers actively participated realizing the ownership of their health. 32 males
      and 49 females (mean age of 40.8 years) were assessed. Among them, 23.4% were
      overweight and obese while 26% reported physical inactivity. Among males, 12.5%
      were smokers. Hypertension and dyslipidaemia were present among 9.9% and 12.3%,
      respectively. 6.2% had high fasting blood glucose values. The program resulted in
      identifying 12 new patients with NCDs. After initiating health promotion
      activities, smoking rate dropped by 75%. Physical inactivity was reduced by 14%
      and consumption of fresh fruits and vegetables increased by 19%. CONCLUSIONS:
      Programs targeting office settings are a new strategy for reduction of NCDs in
      Sri Lanka. True benefit of risk factor modification through BCC programs will
      become apparent in longitudinal assessments.

PMID- 27689597
TI  - Sri Lanka: Adding Ergonomics Dimension in the Health Agenda.

PMID- 27689598
TI  - Ergonomic footwear for Sri Lankan primary schoolchildren: A review of the
      literature.
AB  - BACKGROUND: Foot ailments are common among schoolchildren, some of which may be
      attributed to wearing ill-fitting footwear. As schoolchildren often participate
      in athletic activity, they are doubly vulnerable to foot ailments, and are
      particularly vulnerable to conditions such as hallux valgus, Achilles tendonitis,
      athlete's foot, corns and calluses. Thus, there is an acute need for the design
      and manufacture of ergonomic footwear for this target group. While research on
      appropriate footwear for children has been carried out in relation to child
      populations in other societies, research on the circumstances of Sri Lankan
      schoolchildren is lacking. Neither the requisite design know-how nor the
      information for design is available to footwear manufacturers. OBJECTIVES: This
      review of the literature is aimed at confirming the need for ergonomic footwear
      from the point of view of the effects of wearing ill-fitting shoes and at
      identifying the requirements in terms of design information, especially for
      schoolchildren of the age group five to ten years, to empower footwear
      manufacturers. METHODS: PubMed, Google scholar and Science Direct were used for
      the literature search. RESULTS: 208 publications were read in full, 94 of which
      are referenced in this review. CONCLUSION: The review shows morphological
      measurements, behavior and activity patterns of schoolchildren and environmental
      conditions they are exposed to should be determined to formulate design
      information.

PMID- 27689599
TI  - Ergonomics for enhancing detection of machine abnormalities.
AB  - BACKGROUND: Detecting abnormal machine conditions is of great importance in an
      autonomous maintenance environment. Ergonomic aspects can be invaluable when
      detection of machine abnormalities using human senses is examined. OBJECTIVES:
      This research outlines the ergonomic issues involved in detecting machine
      abnormalities and suggests how ergonomics would improve such detections. METHODS:
      Cognitive Task Analysis was performed in a plant in Sri Lanka where Total
      Productive Maintenance is being implemented to identify sensory types that would
      be used to detect machine abnormalities and relevant Ergonomic characteristics.
      RESULTS AND CONCLUSIONS: As the outcome of this research, a methodology
      comprising of an Ergonomic Gap Analysis Matrix for machine abnormality detection
      is presented.

PMID- 27689600
TI  - Important skills for biomedical services: The perspectives of Malaysian employers
      and employees.
AB  - BACKGROUND: Increase in the occurrence of existing diseases, continual emergence
      of new or exotic diseases and re-emergence of old diseases have placed increasing
      demands on biomedical services in Malaysia. Biomedical technicians play an
      important role in operating biomedical instruments. However, there are no clear
      specifications about characteristics and traits for these semi-professional
      employees. Employers in a few studies claimed that biomedical graduates are not
      ready to enter and face challenges in the job market. OBJECTIVE: Therefore, the
      purpose of this study is to identify technical and generic skills for a
      biomedical technician from the perspectives of the biomedical technicians and
      their employers. METHODS: A quantitative survey design was employed whereby data
      were obtained through the administration of an instrument developed by the
      researchers. The sample consisted of 20 hospital managers and 186 biomedical
      technicians who are currently working in Malaysian government hospitals. RESULTS:
      The findings show that there are no difference in the perceptions of hospital
      managers and biomedical technicians regarding technical and non-technical skills.
      CONCLUSIONS: These findings resulted in a checklist which can be used for
      institutions to produce future biomedical technician graduates in order to meet
      job demands. However, future research is needed to validate the findings and
      explore the variables in depth.

PMID- 27689601
TI  - The aetiologies of Failed Back Surgery Syndrome: A systematic review.
AB  - PURPOSE: Four to fifty percent of patients will develop Failed Back Surgery
      Syndrome (FBSS) following lumbar spine surgery. Repeated surgeries lead to
      escalating costs and subsequent decreases in success rate. Much of the research
      to date has focused on the psychosocial factors associated with FBSS. All factors
      including physical and pathological aetiologies should be examined. These factors
      may be independent, co-exist with or predispose patients to the psychological
      factors associated with FBSS. Previous reviews on the topic have been limited by
      a lack of systematic overview. The aim of this review is to identify the
      physical, physiological and pathological aetiologies of FBSS. METHODS: This
      review was done in accordance with the PRISMA guidelines. A computer-aided search
      of the electronic databases from inception to December 2014 was performed.
      Outcome measures of interest included pain, functional and radiological
      assessments. Two reviewers independently selected studies for inclusion.
      Methodological quality was assessed using the Newcastle Ottawa Scale. RESULTS:
      Six studies met the inclusion criteria and included a total of 663 patients. A
      total of twenty two aetiologies were identified. Only three studies reviewed non
      surgical aetiologies. Many of the studies relied on medical imaging to identify
      the aetiologies. A meta-analysis was not undertaken due to the heterogeneity of
      studies. CONCLUSIONS: The causes of FBSS can be attributed to patho-anatomical,
      peripheral pain generators, physical/ mechanical, neurophysiological, surgical
      and 'other' aetiologies. Three of the studies only examined surgical causes of
      FBSS. Further research, that examines surgical and non-surgical aetiologies, is
      required to draw firm conclusions. With nineteen aetiologies identified, FBSS
      remains an unclear diagnosis for a complex heterogeneous group of patients.

PMID- 27689602
TI  - The clinical factors associated with benefit finding of complementary medicine
      use in patients with back pain: A cross-sectional study with cluster analysis.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) use has been increasing.
      OBJECTIVE: To identify the factors associated with perceived benefit from CAM
      methods in back problems. METHODS: The study was conducted on patients who
      practiced any CAM methods due to complaints of back pain. Social-demographic
      properties, details of CAM methods employed were questioned. Severity of pain was
      measured by visual analog scale (VAS); benefits were evaluated by the Likert
      scale. Hierarchical cluster analysis was used to discover relationships among
      variables. RESULTS: In total, 500 patients (265 female, 235 male) were included
      in the study. Mostly used methods were herbal therapy (32%), balneotherapy (31%),
      cupping (19.4%) and massage-manipulation (19.2%). Of patients, 355 (71%) were
      satisfied. The variables associated with benefit finding were female gender, age,
      chronicity and severity of pain, high educational level, upper middle income
      status, use as a result of recommendation, dissatisfaction with conventional
      methods, residence in an urban area, non-herbal method use, being married, and
      social insurance (p < 0.005). CONCLUSION: The majority of patients using CAM
      perceived benefits; in particular, women living in urban areas, highly educated,
      aged more than 40, who suffer from severe chronic back pain, may be more inclined
      to go to CAM therapists.

PMID- 27689603
TI  - Association of low back pain on physical, sociodemographic and lifestyle factors
      across a general population sample within Greece.
AB  - BACKGROUND: Although low back pain (LBP) is a debilitating problem
      internationally, there is not a lot of research on its impact on physical,
      psychosocial and lifestyle factors. Especially in mediterranean countries, such
      as Greece, it is not sufficiently explored whether physical (pain location,
      activity limitation etc.), sociodemographic (education, smoking etc.) or
      lifestyle factors (i.e. quality of life or anxiety) are influenced by LBP.
      OBJECTIVE: To estimate LBP prevalence in the Greek general population and explore
      its association with particular sociodemographic, physical and lifestyle factors.
      METHOD: A sample of 3125 people of the Greek adult population was randomly
      selected by stratified sampling encompassing rural and urban representation
      within the Greek mainland. An extended survey form was developed entailing three
      sections; personal (sociodemographic) information, questions on symptomatology
      and physical factors (i.e. pain characteristics, recurrence, physical disability
      etc.) and 3 self-administered questionnaires (including mostly lifestyle
      factors); Hospital Anxiety and Depression (HAD) scale for anxiety and depression,
      SF-12 for quality of life (QoL) and Roland-Morris for disability. RESULTS: A
      total of 471 (15%) people reported LBP (210 males, mean age: 47.04 +/- 15.03).
      Amongst them 60% reported sciatica, 76% suffered recurrent LBP and 70% received
      specialist care. Low disability levels, moderate to high pain intensity, gender
      differences and good self-reported QoL and psychosocial status were reported.
      Sociodemographic characteristics (income, smoking, marital status etc.) were not
      associated with LBP physical factors, apart from age which correlated with
      physical disability and wellness (r being 0.446 and 0.405, respectively, p<
      0.001). Physical factors (particularly pain intensity and location) correlated
      with lifestyle factors (QoL) and disability (r ranging between 0.396 and 0.543,
      p< 0.001). Mental wellness, anxiety and depression (as lifestyle factors) were
      not associated with sociodemographic or physical factors. CONCLUSIONS: Physical
      parameters were amongst the most prevalent characteristics of the Greek sample,
      thus offering a direction towards a more targeted treatment and rehabilitation
      planning. Unlike previous literature, most sociodemographic characteristics were
      not correlated with any LBP physical or lifestyle factors, thus possibly
      indicating a different socioeconomic background and aetiology domain to that of
      the usual non-specific LBP spectrum.

PMID- 27689604
TI  - Hip abductor, trunk extensor and ankle plantar flexor endurance in females with
      and without patellofemoral pain.
AB  - BACKGROUND: Previous studies have reported strength deficit in hip abduction,
      extension and external rotation in females with patellofemoral pain (PFP) when
      compared with healthy control; however, there is conflicting evidence for a
      decrease in hip muscle endurance. Therefore, it seems important to evaluate hip
      muscle endurance in females with PFP. Moreover, trunk extensor and ankle plantar
      flexor endurance have not yet been evaluate in females with PFP. OBJECTIVE: To
      compare hip abductor, trunk extensor and ankle plantar flexor endurance between
      females with and without PFP. METHODS: Twenty females with PFP (mean age, 21.1
      years) and 76 healthy females (mean age, 20.5 years) were recruited. Subject
      performed three endurance clinical tests: (1) The hip abductor isometric
      endurance test, (2) The Sorensen test and (3) The heel rise test. Group
      differences were assessed using an independent t tests, or Mann-Whitney U tests
      for non-normally distributed data. RESULTS: Subjects with PFP exhibited
      significantly lower hip abductor, trunk extensor and ankle plantar flexor
      endurance than healthy controls. On average, subjects with PFP had deficits of
      16% in hip abduction, 14% in trunk extension and 26% in ankle plantar flexion.
      CONCLUSION: Females with PFP exhibited diminished hip abductor, trunk extensor
      and ankle plantar flexor endurance compared to healthy controls.

PMID- 27689605
TI  - From Theory to Practice: Engagement in Neurorehabilitation.

PMID- 27689606
TI  - Patient centered care: A path to better health outcomes through engagement and
      activation.
AB  - BACKGROUND: Patient Activation and Health confidence are constructs to assess
      patient engagement and are utilized to encourage patient engagement. A health
      care provider may increase patient engagement further by utilizing behavior
      change theories and models such as the Trans-Theoretical Model of Change (TTM),
      Self-Determination Theory (SDT) and Motivational Interviewing (MI) to realize
      effective and lasting health behavior change by placing accountability
      increasingly on the patient/caregiver to choose to make changes in their health
      behavior on their terms. Reducing or eliminating harmful behaviors such as
      smoking and/or beginning or increasing beneficial health behaviors such as diet
      modification or performance of an exercise program, patients realize improved
      outcomes and better health. PURPOSE: The purpose of this article is to define
      health confidence as a measurement tool for patient engagement, use the TTM as a
      measure of the patient's readiness to change, use TTM, SDT and MI as
      interventional approaches to effect patient change of behavior encouraged by
      physical therapists and incorporate the ICF as a means of identifying barriers
      and facilitators and incorporate the bio-psychosocial model for patient-centered
      care to improve health behavior, health and patient outcomes. CONCLUSION: Patient
      centered care requires involvement of the patient and/or their caregiver at the
      center of the plan. Use of the International Classification of Functioning,
      Disability and Health (ICF) to identify facilitators and barriers unique to the
      patient/caregiver offers another opportunity to successfully engage the patient
      by incorporating the patient's bio-psychosocial support system into care delivery
      and for sustainability. The ICF is a taxonomy and classification system that
      prompts clinicians to identify environmental factors (facilitators and barriers)
      that will influence the patient's ability to perform during therapy session and
      to sustain the interventions and employ suggestions outside of formal therapy
      sessions. Using the facilitators to encourage sustainable change and removing
      barriers, patients are more likely to realize positive health behavior change and
      in turn demonstrate improved outcomes and health as a result of physical therapy
      intervention.

PMID- 27689607
TI  - Building Bridges between healthcare professionals, patients and families: A
      coproduced and integrated approach to self-management support in stroke.
AB  - BACKGROUND: Programmes providing self-management support for patients and
      families are gaining attention and have shown promising outcomes with regards to
      reducing long-term unmet needs post stroke. However, notions of what good self
      management support looks like can differ depending on professional opinion,
      individual preferences, skills and experiences of patients and their families as
      well as on how care and rehabilitation is organised in a particular healthcare
      setting. This resonates with the perspective of patient-centred care, according
      to which the meaning of good care is not universal, but rather jointly shaped
      between healthcare professionals and patients in everyday interactions. While
      self-management support is continuously co-produced in care and rehabilitation
      practices, most self-management programmes are typically provided as an 'add-on'
      to existing statutory care. OBJECTIVE: This paper aims to deepen the
      understanding of how self-management support can be made an integral part of
      everyday care and rehabilitation using Bridges methodology. METHODS: The authors
      provide a self-reflective account on 'Bridges' an integrated approach to self
      management support, which is used by healthcare professionals within acute and
      community stroke rehabilitation across the UK, and in some parts of New Zealand
      and Australia. RESULTS: Bridges is based on self-efficacy principles, but has a
      central aim of professionals sharing decision-making and expertise with patients
      and families in every healthcare interaction. Methodologically, the co-production
      of a Bridges support package with local healthcare professionals and patients is
      critical. The authors present the values articulated by the support package and
      how it engages professionals, patients and Bridges training facilitators in a
      continuous process of adjusting and re-adjusting situated self-management support
      practices. CONCLUSIONS: Our reflections reveal the need to consider development
      and implementation of self-management support as one and the same on-going
      process, if we are to facilitate successful engagement and interest from
      healthcare professionals as well as their patients and families.

PMID- 27689609
TI  - Engagement in social media environments for individuals with who use augmentative
      and alternative communication.
AB  - BACKGROUND: Communicative interactions, despite the mode (e.g., face-to-face,
      online) rely on the communication skills of each individual participating. Some
      individuals have significant speech and language impairments and require the use
      of augmentative and alternative communication (AAC) (i.e., signs, speech
      generating devices) to maximize their communication participation across a
      variety of on and offline contexts. Use of social media has brought about changes
      to communication environments, contributing new contexts for engagement.
      OBJECTIVES: To provide a framework for considering application of engagement
      theory for interventions around social media use by individuals who use AAC.
      METHODS: The author has applied examples from qualitative social media and AAC
      research to a framework of engagement. No formal data collection was used.
      RESULTS: Social media use has become a conventional form of communication. Yet
      recognition of the value of social media (and other electronic modalities) for
      individuals who use AAC has not been fully translated into practice. The examples
      used illustrated how the proposed framework can assist in clinical practice and
      future research directions. CONCLUSION: Engagement, including the proposed
      framework for considerations of social media engagement activities, can provide a
      systematic way to approach social media use for individuals who use AAC.

PMID- 27689608
TI  - Enhanced Medical Rehabilitation: Effectiveness of a clinical training model.
AB  - BACKGROUND: Patient engagement in medical rehabilitation can be greatly
      influenced by their provider during therapy sessions. We developed Enhanced
      Medical Rehabilitation (EMR), a set of provider skills grounded in theories of
      behavior change. EMR utilizes 18 motivational techniques focused on providing
      frequent feedback to patients on their effort and progress and linking these to
      patient goals. OBJECTIVE: To examine the effectiveness of a clinical training
      protocol for clinicians to do EMR, as measured by clinician adherence. METHODS: A
      physical therapist, physical therapist assistant, occupational therapist, and
      certified occupational therapist assistant were trained in EMR. Training
      consisted of five formal training sessions and individual and group coaching.
      Adherence to EMR techniques was measured during two phases: Pre-Training and
      Maintenance, with an a priori target of 90% adherence by clinicians to each EMR
      technique. RESULTS: With training and coaching, clinician adherence per
      therapeutic activity significantly improved in 13 out of 18 items (p < 0.05). The
      target of 90% adherence was not achieved for many items. CONCLUSIONS: Our
      training and coaching program successfully trained clinicians to promote patient
      engagement during therapeutic service delivery, although not typically to 90% or
      greater adherence. Ongoing coaching efforts were necessary to increase adherence.

PMID- 27689610
TI  - What influences acceptability and engagement with a high intensity exercise
      programme for people with stroke? A qualitative descriptive study.
AB  - BACKGROUND: Intensity refers to the amount of effort or rate of work undertaken
      during exercise. People receiving rehabilitation after stroke frequently do not
      reach the moderate to high intensity exercise recommended to maximise gains.
      OBJECTIVE: To explore the factors that influence the acceptability of, and
      engagement with, a high intensity group-based exercise programme for people with
      stroke. METHODS: This qualitative descriptive study included 14 people with
      stroke who had completed a 12-week, high intensity group-based exercise
      rehabilitation programme. Semi-structured interviews were used to explore the
      acceptability of high intensity exercise and the barriers and facilitators to
      engagement. Interviews were recorded, transcribed and analysed using qualitative
      content analysis. RESULTS: The participants found high intensity exercise
      rehabilitation acceptable despite describing the exercise intensity as hard and
      reporting post-exercise fatigue. Participants accepted the fatigue as a normal
      response to exercise, and it did not appear to negatively influence engagement.
      The ease with which an individual engaged in high intensity exercise
      rehabilitation appeared to be mediated by inter-related factors, including:
      seeing progress, sourcing motivation, working hard, the people involved and the
      fit with the person and their life. Participants directly related the intensity
      of their effort to the gains that they made. CONCLUSIONS: In this study, people
      with stroke viewed training at higher intensities as a facilitator, not a
      barrier, to engagement in exercise rehabilitation. The findings may challenge
      assumptions about the influence of exercise intensity on engagement.

PMID- 27689611
TI  - A fine balance and a shared learning journey: Exploring healthcare engagement
      through the experiences of youth with Neuromuscular Disorders.
AB  - BACKGROUND: Youth with Neuromuscular Disorders (NMD) who are wheelchair users can
      now survive well into adulthood if their multisystem comorbidities are prudently
      managed. Uptake of health behaviors may optimize their health outcomes.
      OBJECTIVE: To explore youths' perceptions of health, health behaviors and
      healthcare engagement. METHODS: This qualitative study purposefully recruited 11
      youth with NMD from a concurrent, population-based study for variability of age,
      gender, type of NMD and their ratings of motivation and engagement. Interview
      data were analyzed and synthesized by thematic content. RESULTS: Participants
      perceived healthcare engagement as being given tools (knowledge and
      responsibility) and using them to maintain their finely balanced health. Nested
      in adequate social, emotional and physical support, they took responsibility for
      creatively integrating health behaviors they felt were informed by credible
      knowledge, gained primarily through personal experience. CONCLUSION: Cognizant of
      their compromised health, youth with NMD in this study were motivated to maintain
      their physical health. Limited NMD condition specific knowledge challenged
      youths' uptake of health behaviors. They valued a learning partnership with their
      healthcare professionals. By embracing the youth's experience based knowledge and
      through facilitating supportive relationships, healthcare professionals co
      construct youth's healthcare engagement that may optimize health behaviors and
      outcomes.

PMID- 27689614
TI  - WITHDRAWN: Serum miRNA-203 expression, a potential biomarker for recurrence and
      prognosis in papillary thyroid carcinoma.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 27689612
TI  - Pain, cognition and quality of life associate with structural measures of brain
      volume loss in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is characterized by physical and mental
      impairments that often result in pain and reduced quality of life. OBJECTIVE: To
      understand the relationship of pain, quality of life, and cognition to structural
      measures of brain volume. METHODS: Behavioral measures were assessed in a single
      session using standardized questionnaires and rating scales. Brain volume
      measures were assessed with structural magnetic resonance imaging (MRI). RESULTS:
      Twenty-nine individuals with relapsing-remitting MS and 29 age-matched controls
      participated in this study. Pain, quality of life, and cognition were
      significantly interrelated. Higher fluid attenuation inversion recovery weighted
      lesion volume was significantly associated with increased reports of pain (p =
      0.01), lower physical quality of life (p < 0.0001), and lower cognitive
      performance (p = 0.001) in our cohort. CONCLUSIONS: Assessment of pain and
      quality of life along with structural MRI highlights the importance of
      understanding structure-function relationships in MS and suggests that therapists
      should not only evaluate individuals for cognition and quality of life, but
      should consider rehabilitation goals that target these areas.

PMID- 27689613
TI  - Increased expression ratio of matrix metalloproteinase-9 (MMP9) and tissue
      inhibitor of matrix metalloproteinase (TIMP-1) RNA levels in Iranian multiple
      sclerosis patients.
AB  - OBJECTIVES: Multiple sclerosis (MS) is an autoimmune disease involving the
      central nervous system (CNS) with unknown immunopathogenic mechanisms. Matrix
      metalloproteinase-9 (MMP-9) facilitates T-cell migration into the CNS while the
      tissue inhibitor matrix metalloproteinase-1 (TIMP-1) inhibits MMP-9 actions. The
      aim of this study was to evaluate the expression of TIMP-1 RNA and MMP-9/TIMP-1
      RNA ratio in blood cells of Iranian patients with relapsing-remitting multiple
      sclerosis (RRMS) treated with IFNb. MATERIAL AND METHODS: The study compared the
      expression level of TIMP-1 gene in RRMS samples with normal individuals in Iran
      and the results were compared using a ratio of MMP-9 to TIMP-1. All patients were
      HLA-DRB1*15 negative and were responders to interferon-beta with a normal vitamin
      D level. RESULTS: The RRMS patients manifested a lower expression level of TIMP-1
      RNA than their normal counterparts although the result was not significant (P=
      0.06). Also, the ratio of MMP-9 to TIMP-1 RNA increased significantly (P= 0.009).
      There was no linear correlation between TIMP-1 expression level and risk of
      Expanded Disability Status Scale of Kurtzke (EDSS); nor was there any significant
      correlation between expression status of TIMP-1 and duration of the disease.
      Although there was no significant decrease in TIMP-1 expression level, the MMP
      9/TIMP-1 RNA ratio in RRMS was significantly higher than normal subjects.
      CONCLUSION: Further studies are recommended to compare MMP-9/TIMP-1 RNA ratio in
      patients before and after taking IFN-beta in order to find out if MMP-9/TIMP-1
      RNA ratio can function as a proper marker of the bio efficacy of IFN-beta
      treatment of MS.

PMID- 27689615
TI  - High apelin levels could be used as a diagnostic marker in multiple myeloma: A
      comparative study.
AB  - BACKGROUND: Apelin/APJ system regulates angiogenesis and is overexpressed in some
      malignancies. Apelin can induce lymphangiogenesis and lymph node metastasis.
      OBJECTIVE: We evaluated apelin levels in multiple myeloma (MM) and non-Hodgkin
      lymphoma (NHL); and analyzed the association between apelin levels and clinical
      findings. METHODS: We included consecutive 29 MM, 31 NHL patients, and 19 healthy
      controls. Patients' demographic and clinical features, treatment modalities, and
      responses were recorded from hospital records. Plasma apelin was determined by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: MM patients had significantly
      higher plasma apelin level than NHL and healthy control groups (p< 0.001). Apelin
      level in NHL group was similar to controls (p> 0.05). ROC curve analysis showed
      that the area under the curve value for apelin level in MM was 0.842 ng/ml
      (95%CI: 0.739-0.945, p< 0.001). Plasma apelin level >= 0.827 ng/ml had 76%
      sensitivity and 86% specificity for the diagnosis of MM. Multivariate Cox
      regression analysis showed that MM patients with high apelin level had better
      prognosis and patients with advanced stage of disease (ISS-3) had significantly
      poor prognosis when compared to others. In the MM group, apelin level correlated
      negatively with LDH (r = -0.39, p= 0.038). CONCLUSIONS: In MM, plasma apelin
      level was significantly higher than in NHL and control groups. Apelin could be
      playing a role in MM pathogenesis; and apelin level could be used as a diagnostic
      and prognostic biomarker in MM.

PMID- 27689616
TI  - Glypican-3 and KRT19 are markers associating with metastasis and poor prognosis
      of pancreatic ductal adenocarcinoma.
AB  - OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor
      with metastasis in most patients at diagnosis. The molecular mechanisms
      associated with its high malignancy have not been fully elucidated. This study
      investigated the clinicopathological significances of GPC3 and KRT19 expression
      in PDAC. METHODS: GPC3, KRT19, and CA19-9 protein expression were measured by
      immunohistochemistry. RESULTS: GPC3 and KRT19 protein levels were overexpressed
      in PDAC tumors compared to normal pancreatic tissues, benign pancreatic tissues,
      and peritumoral tissues (P< 0.01). The percentage of positive GPC3 and KRT19
      expression were significantly higher in PDAC patients with larger tumor size,
      poorly differentiated tumor, lymph node metastasis, invasion, and TNM stage
      III/IV disease than in patients with small tumor size, well-differentiated tumor,
      no lymph node metastasis and invasion, as well as TNM stage I/II stage disease
      (P< 0.05 or P< 0.01). Benign pancreatic lesions with positive GPC3 and KRT19
      protein expression exhibited dysplasia or intraepithelial neoplasia. Kaplan-Meier
      survival analysis showed that PDAC patients with positive GPC3 and KRT19
      expression survived significantly shorter than patients with negative GPC3 and
      KRT19 expression (P < 0.05 or P< 0.001). Cox multivariate analysis revealed that
      positive GPC3 and KRT19 expression were independent poor prognosis factors in
      PDAC patients. CONCLUSIONS: GPC3 and KRT19 overexpression are associated with
      carcinogenesis, progression, and poor prognosis in patients with PDAC and a
      valuable biomarker for diagnosis of PDAC.

PMID- 27689617
TI  - Clinical Complexity and Use of Antipsychotics and Restraints in Long-Term Care
      Residents with Parkinson's Disease.
AB  - BACKGROUND: Patients with Parkinson's disease (PD) and/or Parkinsonism are
      affected by a complex burden of comorbidity. Many ultimately require
      institutional care, where they may be subject to the application of physical
      restraints or the prescription of antipsychotic medications, making them more
      vulnerable to adverse outcomes. OBJECTIVES: The objectives of this paper are to:
      1) describe the clinical complexity of older institutionalized persons with PD;
      and 2) examine patterns and predictors of restraint use and prescription of
      antipsychotics in this population. METHODS: Population-based cross-sectional
      cohort study. Residents with PD and/or Parkinsonism living in long-term care
      (LTC) facilities in 6 Canadian provinces and 1 Northern Territory and Complex
      Continuing Care (CCC) facilities in Manitoba and Ontario, Canada. The RAI MDS 2.0
      instrument was used to assess all LTC residents and CCC residents. Clinical
      characteristics and the prevalence of major comorbidities were examined.
      Multivariate modeling was used to identify the characteristics of PD residents
      most associated with the prescription of antipsychotics and the use of restraints
      in LTC and CCC facilities. RESULTS: Residents with PD in LTC and CCC exhibit a
      high prevalence of dementia, major psychiatric disorders, stroke, heart failure,
      chronic obstructive pulmonary disease and diabetes mellitus. More than 90% of LTC
      and CCC residents with PD had cognitive impairment; with more than half having
      moderate to severe impairment. Residents with PD were more likely to receive
      antipsychotics than those without PD. Antipsychotic use was associated with
      psychosis and aggressive behaviours, but also with unsteady gait and higher
      comorbidity and medication count. Similarly, although more common in CCC than LTC
      facilities, both psychosis and aggressive behaviours were associated with
      restraint use, as was greater cognitive and functional impairment, and urinary
      incontinence. Younger age, male gender, and lower physician access were all
      associated with greater antipsychotic and restraint use. CONCLUSIONS: LTC and CCC
      residents with PD are very complex medically. Use of antipsychotics and
      restraints is common, and their use is often associated with factors other than
      psychosis or aggression.

PMID- 27689618
TI  - Assistive Technology for Cognition and Health-related Quality of Life in
      Huntington's Disease.
AB  - BACKGROUND: Assistive technology for cognition (ATC) can be defined as external
      devices aimed at supporting cognitive function. Studies in neurological
      populations suggest that use of ATC is a promising strategy to ameliorate
      negative effects of cognitive impairment and improve Health-related Quality of
      Life (HRQoL). There is a lack of studies on the effects of ATC in HD. OBJECTIVE:
      This study aimed to describe the use of ATC in patients with HD, and to
      investigate the association between ATC and HRQoL. METHODS: A cross-sectional
      population-based study, including eighty-four patients with a clinical HD
      diagnosis (stages I-V). Socio-demographic and clinical data were collected,
      including information regarding various aspects of ATC use and an evaluation of
      cognitive impairment was performed. The Unified Huntington's Disease Rating Scale
      (UHDRS) Total Functional Capacity scale (TFC) and the EQ-5D Visual Analogue Scale
      were used to evaluate functional ability and HRQoL. Descriptive analyses were
      conducted to describe ATC use and regression analyses to investigate associations
      between ATC and HRQoL. RESULTS: Thirty-seven percent of the patients had ATC, and
      ATC was used most frequently in stages I-III. Information about ATC, needs
      evaluation and training was provided to 44%, 32.1% and 20.2% respectively. The
      regression analysis showed a significant association between TFC and HRQoL (beta
      value = -0.564, p = 0.001), but there was no association between ATC and HRQoL.
      CONCLUSIONS: One-third of all patients used ATC, mainly those with mild to
      moderate cognitive impairment (stage I -III). No association between ATC and
      HRQoL was found. More research is needed to investigate effects of ATC in HD.

PMID- 27689621
TI  - Polymorphism in a Cobalt-Based Single-Ion Magnet Tuning Its Barrier to
      Magnetization Relaxation.
AB  - A large barrier to magnetization reversal, a signature of a good single-molecule
      magnet (SMM), strongly depends on the structural environment of a paramagnetic
      metal ion. In a crystalline state, where SMM properties are usually measured,
      this environment is influenced by crystal packing, which may be different for the
      same chemical compound, as in polymorphs. Here we show that polymorphism can
      dramatically change the magnetic behavior of an SMM even with a very rigid
      coordination geometry. For a cobalt(II) clathrochelate, it results in an increase
      of the effective barrier from 109 to 180 cm-1, the latter value being the largest
      one reported to date for cobalt-based SMMs. Our finding thus highlights the
      importance of identifying possible polymorphic phases in search of new, even more
      efficient SMMs.

PMID- 27689620
TI  - Cellular Analysis of Silencing the Huntington's Disease Gene Using AAV9 Mediated
      Delivery of Artificial Micro RNA into the Striatum of Q140/Q140 Mice.
AB  - BACKGROUND: The genetic mutation in Huntington's disease (HD) is a CAG repeat
      expansion in the coding region of the huntingtin (Htt) gene. RNAi strategies have
      proven effective in substantially down-regulating Htt mRNA in the striatum
      through delivery of siRNAs or viral vectors based on whole tissue assays, but the
      extent of htt mRNA lowering in individual neurons is unknown. OBJECTIVE: Here we
      characterize the effect of an AAV9-GFP-miRHtt vector on Htt mRNA levels in
      striatal neurons of Q140/Q140 knock-in mice. METHODS: HD mice received bilateral
      striatal injections of AAV9-GFP-miRHtt or AAV9-GFP at 6 or 12 weeks and striata
      were evaluated at 6 months of age for levels of Htt mRNA and protein and for mRNA
      signal within striatal neurons using RNAscope multiplex fluorescence in situ
      hybridization. RESULTS: Compared to controls, the striatum of 6-month old mice
      treated at 6 or 12 weeks of age with AAV9-GFP-miRHtt showed a reduction of 40-50%
      in Htt mRNA and lowering of 25-40% in protein levels. The number of Htt mRNA foci
      in medium spiny neurons (MSNs) of untreated Q140/Q140 mice varied widely per cell
      (0 to 34 per cell), with ~10% of MSNs devoid of foci. AAV9-GFP-miRHtt treatment
      shifted the distribution toward lower numbers and the percentage of cells without
      foci increased to 14-20%. The average number of Htt mRNA foci per MSN was reduced
      by 43%. CONCLUSIONS: The findings here show that intrastriatal infusion of an
      AAV9-GFP-miRHtt vector lowers mRNA expression of Htt in striatum by ~50%, through
      a partial reduction in the number of copies of mutant Htt mRNAs per cell. These
      findings demonstrate at the neuronal level the variable levels of Htt mRNA
      expression in MSNs and the neuronal heterogeneity of RNAi dependent Htt mRNA
      knockdown.

PMID- 27689619
TI  - Autophagy Activation by Transcription Factor EB (TFEB) in Striatum of HDQ175/Q7
      Mice.
AB  - BACKGROUND: Mutant huntingtin (mHTT) is encoded by the Huntington's disease (HD)
      gene and its accumulation in the brain contributes to HD pathogenesis. Reducing
      mHTT levels through activation of the autophagosome-lysosomal pathway may have
      therapeutic benefit. Transcription factor EB (TFEB) regulates lysosome biogenesis
      and autophagy. OBJECTIVE: To examine if increasing TFEB protein levels in HD
      mouse striatum induces autophagy and influences mHTT levels. METHODS: We
      introduced cDNA encoding TFEB with an HA tag (TFEB-HA) under the control of
      neuron specific synapsin 1 promoter into the striatum of 3 month old HDQ175/Q7
      mice using adeno-associated virus AAV2/9. The levels of exogenous TFEB were
      analyzed using qPCR and Western blot. Proteins involved in autophagy, levels of
      huntingtin, and striatal-enriched proteins were examined using biochemical and/or
      immunohistochemical methods. RESULTS: In HD mice expressing TFEB-HA, HA
      immunoreactivity distributed throughout the striatum in neuronal cell bodies and
      processes and preferentially in neuronal nuclei and overlapped with a loss of
      DARPP32 immunoreactivity. TFEB-HA mRNA and protein were detected in striatal
      lysates. There were increased levels of proteins involved with
      autophagosome/lysosome activity including LAMP-2A, LC3II, and cathepsin D and
      reduced levels of mutant HTT and the striatal enriched proteins DARPP32 and
      PDE10A. Compared to WT mice, HDQ175/Q7 mice had elevated levels of the ER stress
      protein GRP78/BiP and with TFEB-HA expression, increased levels of the astrocyte
      marker GFAP and pro-caspase 3. CONCLUSION: These results suggest that TFEB
      expression in the striatum of HDQ175/Q7 mice stimulates autophagy and lysosome
      activity, and lowers mHTT, but may also increase a neuronal stress response.

PMID- 27689622
TI  - Sophoridine-loaded PLGA microspheres for lung targeting: preparation, in vitro,
      and in vivo evaluation.
AB  - Lung-targeting sophoridine-loaded poly(lactide-co-glycolide) (PLGA) microspheres
      were constructed by a simple oil-in-oil emulsion-solvent evaporation method. The
      obtained microspheres were systematically studied on their morphology, size
      distribution, drug loading, encapsulation efficiency, in vitro release profile,
      and biodistribution in rats. The drug-loaded microparticles showed as tiny
      spheres under SEM and had an average size of 17 MUm with 90% of the microspheres
      ranging from 12 to 24 MUm. The drug loading and encapsulation efficiency were 65%
      and 6.5%, respectively. The in vitro drug release behavior of microspheres
      exhibited an initial burst of 16.6% at 4 h and a sustained-release period of 14
      days. Drug concentration in lung tissue of rats was 220.10 MUg/g for microspheres
      and 6.77 MUg/g for solution after intraveneous injection for 30 min,
      respectively. And the microsphere formulation showed a significantly higher drug
      level in lung tissue than in other major organs and blood samples for 12 days.
      These results demonstrated that the obtained PLGA microspheres could potentially
      improve the treatment efficacy of sophoridine against lung cancer.

PMID- 27689623
TI  - Alarmins and Clinical Outcomes After Major Abdominal Surgery-A Prospective Study.
AB  - PURPOSE: Tissue injury causing immune response is an integral part of surgical
      procedure. Evaluation of the degree of surgical trauma could help to improve
      postoperative management and determine the clinical outcomes. MATERIALS AND
      METHODS: We analyzed serum levels of alarmins, including S100A5, S100A6, S100A8,
      S100A9, S100A11, and S100A12; high-mobility group box 1; and heat-shock protein
      70, after elective major abdominal surgery (n = 82). Blood samples were collected
      for three consecutive days after surgery. The goals were to evaluate the
      relationships among the serum levels of alarmins and selected surgical
      characteristics and to test potential of alarmins to predict the clinical
      outcomes. RESULTS: Significant, positive correlations were found for high
      mobility group box 1 with the length of surgery, blood loss, and intraoperative
      fluid intake for all three days of blood sampling. The protein S100A8 serum
      levels showed positive correlations with intensive care unit length of stay, 28
      day and in-hospital mortality. The protein S100A12 serum levels had significant,
      positive correlations with intensive care unit length of stay, 28-day mortality,
      and in-hospital mortality. We did not find significant differences in alarmin
      levels between cancer and noncancer subjects. CONCLUSION: The high-mobility group
      box 1 serum levels reflect the degree of surgical injury, whereas proteins S100A8
      and S100A12 might be considered good predictors of major abdominal surgery
      morbidity and mortality.

PMID- 27689624
TI  - Subcellular proteomics analysis of different stages of colorectal cancer cell
      lines.
AB  - Studying cell differentiation and transformation allows a better understanding of
      the mechanisms involved in the initiation and the evolution of cancer. The role
      of proteins which participate in these processes is dependent on their location
      within the cell. Determining the subcellular localization of proteins or the
      changes in localization is, therefore, paramount in elucidating their role. Using
      quantitative mass spectrometry, we characterized the protein expression and
      subcellular localization of nearly 5000 proteins from seven different colorectal
      cancer (CRC) cell lines, as well as normal colon fibroblasts and intestinal
      epithelial cells. This cellular characterization allowed the identification of
      colon cancer-associated proteins with differential expression patterns as well as
      deregulated protein networks and pathways. Indeed, our results demonstrate
      differential expression of proteins involved in cell adhesion, cytoskeleton, and
      transcription in colon cancer cells compared to normal colon-derived cells.
      Pathway analyses identified different cellular functions, including endocytosis
      and eIF2 signaling, whose deregulation correlates with mutations found in the
      different CRC phenotypes. Our results provide an unbiased, quantitative and high
      throughput approach to measure changes in protein expression and subcellular
      protein locations in different CRC cell lines.

PMID- 27689625
TI  - The positive net radiative greenhouse gas forcing of increasing methane emissions
      from a thawing boreal forest-wetland landscape.
AB  - At the southern margin of permafrost in North America, climate change causes
      widespread permafrost thaw. In boreal lowlands, thawing forested permafrost peat
      plateaus ('forest') lead to expansion of permafrost-free wetlands ('wetland').
      Expanding wetland area with saturated and warmer organic soils is expected to
      increase landscape methane (CH4 ) emissions. Here, we quantify the thaw-induced
      increase in CH4 emissions for a boreal forest-wetland landscape in the southern
      Taiga Plains, Canada, and evaluate its impact on net radiative forcing relative
      to potential long-term net carbon dioxide (CO2 ) exchange. Using nested wetland
      and landscape eddy covariance net CH4 flux measurements in combination with flux
      footprint modeling, we find that landscape CH4 emissions increase with increasing
      wetland-to-forest ratio. Landscape CH4 emissions are most sensitive to this ratio
      during peak emission periods, when wetland soils are up to 10  degrees C warmer
      than forest soils. The cumulative growing season (May-October) wetland CH4
      emission of ~13 g CH4  m-2 is the dominating contribution to the landscape CH4
      emission of ~7 g CH4  m-2 . In contrast, forest contributions to landscape CH4
      emissions appear to be negligible. The rapid wetland expansion of 0.26 +/- 0.05%
      yr-1 in this region causes an estimated growing season increase of 0.034 +/-
      0.007 g CH4  m-2  yr-1 in landscape CH4 emissions. A long-term net CO2 uptake of
      >200 g CO2  m-2  yr-1 is required to offset the positive radiative forcing of
      increasing CH4 emissions until the end of the 21st century as indicated by an
      atmospheric CH4 and CO2 concentration model. However, long-term apparent carbon
      accumulation rates in similar boreal forest-wetland landscapes and eddy
      covariance landscape net CO2 flux measurements suggest a long-term net CO2 uptake
      between 49 and 157 g CO2  m-2  yr-1 . Thus, thaw-induced CH4 emission increases
      likely exert a positive net radiative greenhouse gas forcing through the 21st
      century.

PMID- 27689626
TI  - Distinct protein and mRNA kinetics of skeletal muscle proton transporters
      following exercise can influence interpretation of adaptations to training.
AB  - NEW FINDINGS: What is the central question of this study? Following a training
      intervention, how is the interpretation of adaptations in skeletal muscle H+
      transporters influenced by biopsy timing in the context of individual protein and
      mRNA kinetics after the final exercise bout? What is the main finding and its
      importance? We show that distinct postexercise protein and mRNA kinetics for
      monocarboxylate transporter 1/4 and sodium-hydrogen exchanger 1 indicate that
      timing of a single end-point biopsy after a training intervention can influence
      the inferences made. Furthermore, we found the intrasubject, intersample
      variability of the muscle buffer capacity titration assay to be greater than the
      typical training effect. In order to gain a better understanding of training
      induced adaptations in skeletal muscle pH regulation, in this study we measured
      protein and mRNA kinetics of proton (H+ ) transporters for 72 h following a bout
      of high-intensity interval exercise (HIIE), conducted after 4 weeks of similar
      training. We also assayed muscle buffer capacity (betam) by a titration technique
      (betamin vitro ) over the same period. Sixteen active men cycled for seven bouts
      of 2 min at ~80% of peak aerobic power, interspersed with 1 min rest. Compared
      with the first 9 h postexercise, monocarboxylate transporter (MCT) 1 protein
      content was ~1.3-fold greater 24-72 h post-HIIE, whereas there was no such change
      in MCT4 protein content. Conversely, MCT1 and MCT4 mRNA expression progressively
      decreased 9-72 h post-HIIE. Sodium-hydrogen exchanger 1 (NHE1) protein content
      was lower 9 h post-HIIE (~0.8-fold) compared with every other postexercise time
      point, but NHE1 mRNA expression was 2.2 to 2.9-fold greater 24-72 h post-HIIE,
      compared with the first 24 h post-HIIE. Furthermore, we determined the
      intrasubject, intersample variability (11.5%) of betamin vitro for resting
      samples taken on consecutive days to be greater than the typical training effect
      (mean 6%; 95% confidence limits +/-4%). In conclusion, the delay in steady-state
      protein turnover should inform biopsy timing in studies investigating the
      response to training of the H+ transport proteins, whereas the temporal
      resolution provided by single time points has been shown to be of limited
      epistemological value for their corresponding mRNA expression. Finally, our data
      cast doubt on the ecological validity of the betamin vitro assay for measuring
      true changes in betam.

PMID- 27689628
TI  - Why nurses leave.
AB  - 'I left because I was utterly exhausted. I was frustrated because I couldn't do
      the job properly, I wasn't nursing, I was trying to survive each shift. When I
      asked for help nobody was interested; not being able to cope was seen as my
      personal failure. When I offered advice no-one listened; management simply didn't
      care about me, my views, or the care we were giving to patients.' These comments
      came from a nurse who, after six years as a sister in an acute medical ward, left
      nursing to join a large pharmaceutical company. Now she feels part of a team,
      valued by management and encouraged to take part in continuing education to meet
      new demands and responsibilities.

PMID- 27689629
TI  - ?
AB  - Splashing about: Physiotherapist and client making waves in a hydrotherapy pool
      on display at the Healthcare "91 Exhibition in Birmingham last week.

PMID- 27689627
TI  - Incidence Rate of Prediabetes Progression to Diabetes: Modeling an Optimum Target
      Group for Intervention.
AB  - Thirty-seven percent of US adults have prediabetes. Various interventions can
      delay diabetes progression; however, the optimum target group for risk reduction
      is uncertain. This study estimated rate of progression to diabetes at 1 and 5
      years among a cohort of patients from 3 primary care clinics and modeled the
      potential magnitude in diabetes incidence risk reduction of an intervention
      program among specific subgroups. Records of 106,821 empaneled patients in 2005
      were reviewed. Generalized population attributable risk (PAR) statistics were
      calculated to estimate the impact of reducing fasting blood glucose on diabetes
      progression. Multiple intervention effects (varying levels of glucose reduction
      along with multiple adherence rates) were examined for those with baseline
      glucose from 110 to 119 mg/dL and >=120 mg/dL. Ten percent of patients (n =
      10,796) met criteria for prediabetes. The 1- and 5-year diabetes incidence rate
      was 38.6 and 40.24 per 1000 person-years, respectively. Age and obesity were
      independent predictors of increased progression rate. The generalized PAR for a
      10-point reduction in the 110-119 mg/dL subgroup with 25% adherence was 7.6%. The
      generalized PAR for similar percent reduction and adherence level in patients
      with baseline glucose of >=120 mg/dL was only 3.0%. Rate of progression to
      diabetes increased over time and with associated independent risk factors.
      Greater risk reduction in diabetes progression within the target population can
      be achieved when the intervention is successful in those with baseline glucose of
      110-119 mg/dL. Modeling an optimum target group for a diabetes prevention
      intervention offers a novel and useful guide to planning and allocating resources
      in population health management.

PMID- 27689630
TI  - Community health.
AB  - Nurses' unions last week criticised as 'window dressing' Glasgow Health Board's
      new community health strategy which proposes to 'boost' health promotion work.
      But Scottish Health Visitors' Association General Secretary David Forbes said:
      'The draft documents suggest that health visiting time will be halved for all
      clients.'

PMID- 27689631
TI  - Employment conditions 'have worsened'.
AB  - NHS Trusts have only changed nurses' employment conditions for the worse, an RCN
      survey revealed last week.

PMID- 27689632
TI  - RCN defends itself against criticism.
AB  - The Royal College of Nursing has strongly defended its legal action against the
      News of the World in the controversial Nurse Lim case, in response to criticism
      from the newspaper.

PMID- 27689633
TI  - Ashworth opens inquiry into MIND allegations.
AB  - Ashworth Hospital has launched a high- level internal inquiry after allegations
      by MIND, the mental health charity, that nurses showed pornographic films to
      patients.

PMID- 27689634
TI  - ?
AB  - Health minister Virginia Bottomley revealed at a conference last week that the
      Government is set to crack down on poor standards in smaller residential homes by
      closing a loophole in the Registered Homes Act which placed small units outside
      their control.

PMID- 27689635
TI  - Millions of pounds 'are wasted' by training cuts.
AB  - More than L3m earmarked for training health visitors is 'going to waste' because
      the number of students being sponsored by health authorities this year has been
      cut by a third, the Health Visitors' Association has claimed.

PMID- 27689636
TI  - Study finds midwives' time is often wasted.
AB  - Midwives are often on duty at the wrong time, in the wrong place and spend less
      than 50 per cent of their working time providing maternity care, a new study
      based on a Yorkshire hospital's staff activity forms has found.

PMID- 27689637
TI  - Reformed health services 'must safeguard equality'.
AB  - Health authorities and NHS Trusts are being asked to give a written commitment to
      safeguard racial equality in the reformed health service.

PMID- 27689638
TI  - Trevor clay scholarship.
AB  - RCN membersare invited to apply for a Trevor Clay Scholarship worth L4,000 for
      nursing study or research.

PMID- 27689639
TI  - ?
AB  - Jean Hooper, currently Principal of the Solent School of Health Studies and
      English National Board Chair, has been appointed Professor of Nursing Education
      at Portsmouth Polytechnic.

PMID- 27689640
TI  - Sickle cell pain control is poor'.
AB  - Services in South London hospitals for people with sickle cell disease have come
      under attack following conflict about inadequate levels of pain control.

PMID- 27689641
TI  - Midwives should be first contact.
AB  - One in ten mothers have their first contact with a midwife at the time of birth,
      the results of a Gallup Poll show.

PMID- 27689642
TI  - ?
AB  - Cancer care: Tom Bolger (left), Gill Oliver, Viscount Tonypandy, Susie Wilkinson
      and Sheila MacBride launch the RCN's Standards of Care in Cancer Nursing.

PMID- 27689644
TI  - Increase in day cases.
AB  - The number of NHS day-case patients has increased significantly over the past
      year. A recent survey of district health and family health service authorities
      showed an 8.5 per cent increase in the number of day-case patients treated in the
      1990-1991 financial year.

PMID- 27689643
TI  - Cancer nursing guidelines.
AB  - National guidelines for cancer nursing were launched last week by the Royal
      College of Nursing as part of its Standards of Care series.

PMID- 27689645
TI  - Queen rewards nurses' outstanding work.
AB  - More than 40 nurses were honoured in the Queen's Birthday Honours list, with two
      receiving the Order of the British Empire.

PMID- 27689647
TI  - London services may be pared.
AB  - Health Secretary William Waldegrave is bracing himself to tackle the
      restructuring of London's teaching hospitals.

PMID- 27689646
TI  - ?
AB  - Public appeal: Martyn Lewis, BBC news presenter and Director of the Cancer Relief
      Macmillan Fund, has launched an appeal to raise the .C2.5 million needed to
      build, equip and operate a new home for St Nicholas' Hospice in Bury St Edmunds.

PMID- 27689651
TI  - World news.
AB  - United States The Center for Disease Control in America is said to be close to
      formally recommending universal vaccination against hepatitis B.

PMID- 27689649
TI  - Parliament.
AB  - Multi-million pound savings on the National Health Service's purchasing bills arc
      being sought following allegations of negligence and incompetence.

PMID- 27689652
TI  - ?
AB  - Italy Between nine and 11 million adults worldwide could be infected with HIV -
      and this figure could be an underestimate - the seventh international AIDS
      conference in Florence heard last week.

PMID- 27689653
TI  - Sport as a factor in severe eye injuries.
AB  - Sport is the most common cause of severe eye injury in Britain, and the incidence
      seems to be increasing.

PMID- 27689654
TI  - Aspirin prevents fetal growth retardation.
AB  - Aspirin is effective in preventing fetal growth retardation, French researchers
      have found.

PMID- 27689655
TI  - Stress prevention may reduce cot deaths.
AB  - Understanding how babies respond to overheating and other forms of stress may
      help to prevent cot deaths, research funded by the Foundation for the Study of
      Infant Deaths has shown.

PMID- 27689656
TI  - Most men reluctant to seek advice on BPH.
AB  - Most men suffering from the symptoms of benign prostatic hypertrophy (BPH) say
      they are willing to consult a nurse about the problem, but only two per cent do.
      A national survey by the British Market Research Bureau, which questioned 998 men
      over the age of 50, found that although the symptoms of BPH were widespread,
      knowledge of the condition and its treatment was poor.

PMID- 27689657
TI  - Vaccine to prevent the spread of malaria.
AB  - A vaccine which might halt the transmission of malaria could be ready to undergo
      human trials within two years.

PMID- 27689659
TI  - 'Safer sex' may increase hepatitis A infection.
AB  - The adoption of safer sexual practices might lead to an increase in acute
      infection with hepatitis A.

PMID- 27689658
TI  - Asthma mortality increase questioned.
AB  - There is no evidence for an increase in . asthma mortality in children between
      1979 and 1989.

PMID- 27689660
TI  - Critical age for childbearing.
AB  - The probability of conception falls rapidly after the age of 31 and the
      probability of an adverse pregnancy outcome increases about the same time.

PMID- 27689661
TI  - Gentamicin resistance causing concern.
AB  - Screening for strains of high-level gentamicin-resistant E faeciumshould be
      initiated, following their first appearance outside the United States.

PMID- 27689662
TI  - Emotional rescue.
AB  - Virtually every home boasts at least one picture on its walls. We hang them
      because we like the image portrayed or because they demand our attention. Just
      looking at pictures can be therapeutic, but the therapeutic effect of producing
      them is less well acknowledged.

PMID- 27689663
TI  - On extended loan only.
AB  - Megan Edwards had never had any intention of becoming a nurse. She was more
      interested in domestic science as a teenager in a village in North Wales.

PMID- 27689664
TI  - Speaking out against abortion.
AB  - In response to Abortion and nurses who say no (Nursing Standard Letters, June
      12), I appeal to nurses who participate in abortions to examine their practice in
      terms of the UK Central Council's Code of Professional Conduct.

PMID- 27689665
TI  - Another view of conversion.
AB  - After reading the view of conversion courses (Nursing Standard Points of View,
      June 12) I feel that, as I have completed such a course, I could offer a more
      experienced point of view.

PMID- 27689666
TI  - Pick on someone your own size.
AB  - I've had a weight problem all my life, but it has never stopped me doing anything
      my thinner and supposedly fitter colleagues have done.

PMID- 27689667
TI  - Only joking.
AB  - I would like it to be known that my recent article (Nursing StandardPoints of
      View, June 12) was meant entirely as a humourous piece, and should in no way be
      taken as a slight against anyone working for the South West Manchester College of
      Nursing, whether they be tutors, administrative personnel or librarians.

PMID- 27689669
TI  - Cutting out the eyewash.
AB  - I was most interested in the article Conjunctival Swabs: assessment of value
      (Nursing Standard May 29).

PMID- 27689668
TI  - Some more equal than others?
AB  - I have been to RCN Congress many times in the past 10 years and, I think, there
      has always been an item on the agenda concerning the problems of enrolled nurses
      who wish to convert.

PMID- 27689670
TI  - Information exchange.
AB  - I am a staff nurse on a mixed general surgical ward. My colleagues and I are
      considering the implementation of primary nursing, and would be grateful for any
      information on its successful use in the surgical field. We would also appreciate
      the opportunity to visit any surgical ward which has implemented primary nursing.

PMID- 27689671
TI  - A month in pictures.
AB  - We've seen some remarkable costumes and props during the past month's events.

PMID- 27689672
TI  - AIDS - A strategy for nursing care AIDS - A strategy for nursing care 3 R Pratt
      Edward Arnold 280pp L9.95 0-340-54841-X [Formula: see text].
AB  - Those of us who work with people with HIV eagerly awaited the third edition of
      Pratt's book. When I got the first edition of AIDS - A Strategy for Nursing Care,
      in 1986, I remember what a lifeline it was in this confusing 'new' field. The
      second edition came out in 1988 and provided us with a more comprehensive book,
      which included more about the organisation of HIV care with models and a
      philosophy emanating from the Riverside experience in London.

PMID- 27689673
TI  - HIV roundup.
AB  - A survey of AIDS education in secondary schools This survey on the provision of
      AIDS education in secondary schools in South East England is the second phase of
      the HIV/AIDS Education and Young People Project. Results include.

PMID- 27689674
TI  - Listings.
AB  - Nursing Standard regrets that owing to unprecedented demand we are no longer able
      to take listings over the telephone. We would like to remind our readers that the
      listings section is for use by charitable organisations, unions, professional
      organisations and health authorities to publicise forthcoming events. Your
      listings should contain all relevant details and be posted or faxed to Clare
      Ward, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex
      HA1 2AX (Fax 081-423 3867).

PMID- 27689676
TI  - New Pathways for the Dual Gold-Catalyzed Cyclization of Diynes.
AB  - The reaction of thiophene-based diynes with dual-activation gold catalysts can
      provide cyclobutene derivatives or different polycycles by selective C-H
      insertion reactions. Also, the first sigma,pi-digold diyne complex was obtained
      in a stoichiometric reaction, providing insight into the dual activation
      mechanism. The new products were unambiguously identified by X-ray single-crystal
      structure analysis.

PMID- 27689675
TI  - Fall Risk Assessment Predicts Fall-Related Injury, Hip Fracture, and Head Injury
      in Older Adults.
AB  - OBJECTIVES: To investigate the role of a fall risk assessment, using the Downton
      Fall Risk Index (DFRI), in predicting fall-related injury, fall-related head
      injury and hip fracture, and death, in a large cohort of older women and men
      residing in Sweden. DESIGN: Cross sectional observational study. SETTING: Sweden.
      PARTICIPANTS: Older adults (mean age 82.4 +/- 7.8) who had a fall risk assessment
      using the DFRI at baseline (N = 128,596). MEASUREMENTS: Information on all fall
      related injuries, all fall-related head injuries and hip fractures, and all-cause
      mortality was collected from the Swedish Patient Register and Cause of Death
      Register. The predictive role of DFRI was calculated using Poisson regression
      models with age, sex, height, weight, and comorbidities as covariates, taking
      time to outcome or end of study into account. RESULTS: During a median follow-up
      of 253 days (interquartile range 90-402 days) (>80,000 patient-years), 15,299
      participants had a fall-related injury, 2,864 a head injury, and 2,557 a hip
      fracture, and 23,307 died. High fall risk (DFRI >=3) independently predicted fall
      related injury (hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.39
      1.49), hip fracture (HR = 1.51, 95% CI =1.38-1.66), head injury (HR = 1.12, 95%
      CI = 1.03-1.22), and all-cause mortality (HR = 1.39, 95% CI = 1.35-1.43). DFRI
      more strongly predicted head injury (HR = 1.29, 95% CI = 1.21-1.36 vs HR = 1.08,
      95% CI = 1.04-1.11) and hip fracture (HR = 1.41, 95% CI = 1.30-1.53 vs HR = 1.08,
      95% CI = 1.05-1.11) in 70-year old men than in 90-year old women (P < .001).
      CONCLUSION: Fall risk assessment using DFRI independently predicts fall-related
      injury, fall-related head injury and hip fracture, and all-cause mortality in
      older men and women, indicating its clinical usefulness to identify individuals
      who would benefit from interventions.

PMID- 27689677
TI  - Highly Transparent Conducting Nanopaper for Solid State Foldable Electrochromic
      Devices.
AB  - It is of great challenge to develop a transparent solid state electrochromic
      device which is foldable at the device level. Such devices require delicate
      designs of every component to meet the stringent requirements for transparency,
      foldability, and deformation stability. Meanwhile, nanocellulose, a ubiquitous
      natural resource, is attracting escalating attention recently for foldable
      electronics due to its extreme flexibility, excellent mechanical strength, and
      outstanding transparency. In this article, transparent conductive nanopaper
      delivering the state-of-the-art electro-optical performance is achieved with a
      versatile nanopaper transfer method that facilitates junction fusing for high
      quality electrodes. The highly compliant nanopaper electrode with excellent
      electrode quality, foldability, and mechanical robustness suits well for the
      solid state electrochromic device that maintains good performance through
      repeated folding, which is impossible for conventional flexible electrodes. A
      concept of camouflage wearables is demonstrated using gloves with embedded
      electrochromics. The discussed strategies here for foldable electrochromics serve
      as a platform technology for futuristic deformable electronics.

PMID- 27689678
TI  - Acute calcium kinetics in haemodialysis patients.
AB  - INTRODUCTION: To avoid excessive calcium loading in haemodialysis (HD) patients,
      current guidelines suggest a dialysate calcium concentration (dCa) of 2.5 mEq/L
      based on relatively stable intradialytic serum calcium levels. However, the
      latter do not account for possible calcium storage in acutely accessible pools. A
      rapidly exchangeable calcium pool located at the bone level has been previously
      proposed to be involved in acute (minute-to-minute) extracellular calcium
      regulation. DESIGN: To evaluate the contribution of this pool in the maintenance
      of serum calcium levels, acute calcium buffer capacity was assessed by measuring
      intradialytic dialysate-sided ionized calcium mass balance (iCaMB ) and change in
      extracellular fluid calcium mass in chronic HD patients using a dCa of 3.5 (n =
      28) and 2.5 (n = 10) mEq/L. Serum osteocalcin, the most abundant noncollagenous
      bone protein, was measured before the HD session. RESULTS: iCaMB was invariably
      positive for both 2.5 and 3.5 mEq/L dCa, with a mean of 434 (+/-125) and 725 (+/
      162) mg/HD, respectively (P < 0.001). Buffered intradialytic calcium load was 410
      (+/-116) and 565 (+/-130) mg/HD, and acute calcium buffer capacity was 95 (+/-8)%
      and 78 (+/-7)% (mean values at 2.5 and 3.5 mEq/L dCa, respectively) (P < 0.001).
      Using 3.5 mEq/L dCa, an independent association of acute calcium buffer capacity
      with undercarboxylated osteocalcin (beta = 0.512, P = 0.002) was demonstrated.
      CONCLUSIONS: Our data strongly suggest the existence of a rapidly exchangeable
      calcium pool that counteracts acute serum calcium deviations in HD patients. This
      study provides, for the first time, experimental evidence for the involvement of
      bone in acute extracellular calcium regulation in vivo.

PMID- 27689679
TI  - A Star-shaped Oligo(phenylenevinylene) Liquid Crystal Host with an Anthracene
      Guest-A Double Nanosegregating Supermesogen.
AB  - Hexasubstituted C3 -symmetric benzenes with three elongated shape-persistent
      oligo(phenylenevinylene) arms and three pyridyl hydrogen-bond acceptors have been
      synthesized. These mesogens assemble in a double-helical columnar liquid crystal
      (LC) structure, owing to the compensation of free spaces between conjugated arms
      by dimer formation. The void is filled also by up to three anthracene carboxylic
      acids as guests forming hydrogen bonded supermesogens assembling in columnar LC
      and soft-crystal phases. Thin film fluorescence and solid-state NMR spectroscopy
      imply a transition from a disordered columnar LC to an unexpected double
      nanosegregated morphology of a filled soft columnar crystal phase. An additional
      intracolumnar separation of anthracene and oligo(phenylenevinylene) chromophores
      occurs, separate to the general segregation of aliphatic and aromatic building
      blocks in LC structures. The new type of supermesogens will enable the rational
      design of host-guest double cables with a wide range of different conjugated
      building blocks.

PMID- 27689680
TI  - Synthesis and Reactivity of Discrete Calcium Imides.
AB  - Protonolysis of dibenzylcalcium with triphenylsilylamine affords a thf
      coordinated tetrametallic calcium imide with a heterocuboid core structure. The
      use of calcium bis(tetramethylaluminate) as a precursor for tandem salt
      metathesis/protonolysis reactions with alkali metal amides of 2,6
      diisopropylaniline and triphenylsilylamine provides access to Lewis acid
      stabilized monocalcium imides of the type [(thf)4 Ca(MU2 -NR)(MU2 -Me)AlMe2 ].
      Treatment of [(thf)4 Ca(MU2 -NSiPh3 )(MU2 -Me)AlMe2 ] with phenylsilane results
      in H-Si addition across the Ca-N imido bond, producing a homoleptic calcium
      amidoaluminate complex and putative CaH2 whereas reaction with phenylacetylene
      leads to protonation of an AlMe moiety to yield the dimeric complex
      [(thf)Ca{NSiPh3 }{AlMe2 (CCPh)}]2 .

PMID- 27689681
TI  - Gold Nanorods, DNA Origami, and Porous Silicon Nanoparticle-functionalized
      Biocompatible Double Emulsion for Versatile Targeted Therapeutics and Antibody
      Combination Therapy.
AB  - Gold nanorods, DNA origami, and porous silicon nanoparticle-functionalized
      biocompatible double emulsion are developed for versatile molecular targeted
      therapeutics and antibody combination therapy. This advanced photothermal
      responsive all-in-one biocompatible platform can be easily formed with great
      therapeutics loading capacity for different cancer treatments with synergism and
      multidrug resistance inhibition, which has great potential in advancing
      biomedical applications.

PMID- 27689682
TI  - Developmental study identifies the ages at which the processes involved in the
      perception of verticality and in postural stability occur.
AB  - AIM: The aim of this study was to understand the role played by visual
      information on the development of verticality and postural stability in healthy
      children. METHODS: The study comprised 66 healthy children from 4.0 to 15.7 years
      of age. Postural performances were recorded with a TechnoConcept platform. At the
      same time, the children's perception of subjective visual vertical (SVV) was
      recorded while they adjusted a vertical fluorescent line, either in the dark or
      in the presence of perturbing visual stimuli. Two testing control conditions
      without an SVV task were also performed by all of the children: static
      posturographic recording with open eyes and closed eyes. RESULTS: Postural
      measurements provided evidence of a correlation between the children's age and
      the tasks performed. Postural stability improved with age until eight to nine
      years, and SVV performance improved after 10-11 years. After these ages, postural
      and SVV capabilities did not change until at least 15 years of age. CONCLUSION:
      Our findings suggest that the maturation of cortical and central processes
      involved in both the perception of verticality and in postural stability took
      place during childhood. However, maturation occurred later for vertical
      perception, which could imply delayed maturation of sensory integration
      processes.

PMID- 27689683
TI  - Shock wave treatment after hindlimb ischaemia results in increased perfusion and
      M2 macrophage presence.
AB  - Shock wave therapy (SWT) has been shown to induce angiogenesis in ischaemic
      muscle. However, the mechanism of action remains unknown. Macrophages are crucial
      for angiogenic responses after ischaemic injury. The M2 macrophage subset enables
      tissue repair and induces angiogenesis. It was hypothesized that the angiogenic
      effects of SWT are at least partly caused by enhanced macrophage recruitment.
      C57BL/6 mice were subjected to hind limb ischaemia with subsequent SWT or sham
      treatment. Muscles were analysed via immunofluorescence staining, reverse
      transcription polymerase chain reaction and western blot. Gene expression and
      proteins involved in macrophage recruitment were analysed and tissue sections
      were stained for macrophages, including subsets, capillaries and arterioles.
      Laser Doppler perfusion imaging was performed to assess functional outcome.
      Treated muscles showed increased expression of the pivotal macrophage recruiting
      factor monocyte chemotactic protein 1 (MCP-1). Higher levels of macrophage marker
      CD14 were found. Increased numbers of macrophages after SWT could be confirmed by
      immunofluorescence staining. The expression of the M2 polarization promoting
      chemokine interleukin 13 was significantly elevated in the treatment group.
      Elevated mRNA expression of the M2 scavenger receptor CD163 was found after SWT.
      Immunofluorescence staining confirmed increased numbers of M2 macrophages after
      treatment. It was found that SWT resulted in higher number of capillaries and
      arterioles. Assessment of functional outcome revealed significantly improved limb
      perfusion in treated animals. Shock wave therapy causes increased macrophage
      recruitment and enhanced polarization towards reparative M2 macrophages in
      ischaemic muscle resulting in angiogenesis and improved limb perfusion and
      therefore represents a promising new treatment option for the treatment of
      ischaemic heart disease. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27689684
TI  - Understanding protein glycosylation pathways in bacteria.
AB  - Through advances in analytical methods to detect glycoproteins and to determine
      glycan structures, there have been increasing reports of protein glycosylation in
      bacteria. In this review, we summarize the known pathways for bacterial protein
      glycosylation: lipid carrier-mediated 'en bloc' glycosylation; and cytoplasmic
      stepwise protein glycosylation. The exploitation of bacterial protein
      glycosylation systems, especially the 'mix and match' of three independent but
      similar pathways (oligosaccharyltransferase-mediated protein glycosylation,
      lipopolysaccharide and peptidoglycan biosynthesis) in Gram-negative bacteria for
      glycoengineering recombinant glycoproteins is also discussed.

PMID- 27689685
TI  - Bioaccessibility of Fukushima-Accident-Derived Cs in Soils and the Contribution
      of Soil Ingestion to Radiation Doses in Children.
AB  - Ingestion of contaminated soil is one potential internal exposure pathway in
      areas contaminated by the Fukushima Daiichi Nuclear Power Plant accident. Doses
      from this pathway can be overestimated if the availability of radioactive
      nuclides in soils for the gastrointestinal tract is not considered. The concept
      of bioaccessibility has been adopted to evaluate this availability based on in
      vitro tests. This study evaluated the bioaccessibility of radioactive cesium from
      soils via the physiologically-based extraction test (PBET) and the extractability
      of those via an extraction test with 1 mol/L of hydrochloric acid (HCl). The
      bioaccessibility obtained in the PBET was 5.3% +/- 1%, and the extractability in
      the tests with HCl was 16% +/- 3%. The bioaccessibility was strongly correlated
      with the extractability. This result indicates the possibility that the
      extractability in HCl can be used as a good predictor of the bioaccessibility
      with PBET. In addition, we assessed the doses to children from the ingestion of
      soil via hand-to-mouth activity based on our PBET results using a probabilistic
      approach considering the spatial distribution of radioactive cesium in Date City
      in Fukushima Prefecture and the interindividual differences in the surveyed
      amounts of soil ingestion in Japan. The results of this assessment indicate that
      even if children were to routinely ingest a large amount of soil with relatively
      high contamination, the radiation doses from this pathway are negligible compared
      with doses from external exposure owing to deposited radionuclides in Fukushima
      Prefecture.

PMID- 27689686
TI  - Recombinant exochitinase of the thermophilic mould Myceliopthora thermophila BJA:
      Characteristics and utility in generating N-acetyl glucosamine and in biocontrol
      of phytopathogenic fungi.
AB  - Chitinase from the thermophilic mould Myceliopthora thermophila BJA (MtChit) is
      an acid tolerant, thermostable and organic solvent stable biocatalyst which does
      not require any metal ions for its activity. To produce high enzyme titres,
      reduce fermentation time and overcome the need for induction, this enzyme has
      been heterologously expressed under GAP promoter in the GRAS yeast, Pichia
      pastoris. The production medium supplemented with the permeabilizing agent Tween
      20 supported two-fold higher rMtChit production (5.5 * 103 U L-1 ). The consensus
      sequences S(132)xG(133)G(134) and D(168)xxD(171)xD(173)xE(175) in the enzyme have
      been found to represent the substrate binding and catalytic sites, respectively.
      The rMtChit, purified to homogeneity by a two-step purification strategy, is a
      monomeric glycoprotein of ~48 kDa, which is optimally active at 55 degrees C and
      pH 5.0. The enzyme is thermostable with t1/2 values of 113 and 48 min at 65 and
      75 degrees C, respectively. Kinetic parameters Km , Vmax , kcat , and kcat /Km of
      the enzyme are 4.655 mg mL-1 , 34.246 nmol mg-1  s-1 , 3.425 * 106 min-1 , and
      1.36 * 10-6 mg mL-1  min-1 , respectively. rMtChit is an unique exochitinase,
      since its action on chitin liberates N-acetylglucosamine NAG. The enzyme inhibits
      the growth of phytopathogenic fungi like Fusarium oxysporum and Curvularia
      lunata, therefore, this finds application as biofungicide at high temperatures
      during summer in tropics. (c) 2016 American Institute of Chemical Engineers
      Biotechnol. Prog., 33:70-80, 2017.

PMID- 27689687
TI  - Pineal cysts-A benign association with familial retinoblastoma.
AB  - Patients with familial/heritable retinoblastoma (RB) are at increased risk of
      developing second malignancies throughout life, including a pineoblastoma
      (trilateral RB [TRB]) in early childhood. Current guidelines recommend regular
      surveillance brain imaging for those with heritable RB until 5 years of age. The
      presence of pineal cysts has been reported in patients with RB. Pineal cysts are
      thought to arise due to focal degeneration of the pineal gland and can be found
      incidentally. The finding of pineal abnormalities including cysts in children
      with RB on imaging is disconcerting, as it raises the possibility of an
      underlying malignancy, specifically a pinealoblastoma. The authors reviewed the
      imaging findings and clinical significance of pineal cysts in 69 patients
      diagnosed with RB at our center between December 1999 and November 2015. Twenty
      six patients had pineal cysts found on brain magnetic resonance imaging (MRI)
      scans performed either at diagnosis or follow-up. Thirty-eight of 69 patients had
      underlying heritable RB. Nineteen of 38 familial RB patients had a pineal cyst
      compared with 3 out of 26 with sporadic RB (P = .004). In the majority, the
      imaging characteristics and size of the cysts remained stable or resolved. In
      this cohort, pineal cysts were detected at significantly increased frequency in
      heritable RB. This may be a benign association or may reflect abnormal underlying
      biology of pineal tissue in individuals highly susceptible to malignancy. Imaging
      characteristics can be helpful in distinguishing between benign and malignant
      lesions. The presence of a pineal cyst in patients with unilateral disease may be
      a useful indicator of underlying heritable RB.

PMID- 27689689
TI  - Evidence for phase-based psychotherapy as a treatment for dissociative identity
      disorder comorbid with major depressive disorder and alcohol dependence.
AB  - We report on the treatment and successful outcome of a 58-year-old Native
      American male with a history of complex trauma presenting with dissociative
      identity disorder (DID) and major depressive disorder. The treatment included a
      trauma-informed phase-based psychotherapy as recommended by the International
      Society for the Study of Trauma and Dissociation for treating DID. We assessed
      symptoms at baseline and at three additional time points over the course of 14
      months. We utilized the Reliable Change Index to examine statistically
      significant change in symptoms over the course of treatment. Significant symptom
      improvements were realized posttreatment across all measured domains of
      functioning, including dissociative symptoms, alcohol abuse, depression, anxiety,
      and emotion regulation skills. Moreover, the client no longer met criteria for
      DID, major depressive disorder, or alcohol abuse. Results are discussed in terms
      of the effectiveness of trauma-focused, phase-based treatment for DID for cases
      of complex trauma with comorbid disorders.

PMID- 27689690
TI  - The effect of cushion properties on skin temperature and humidity at the body
      support interface.
AB  - The purpose of this study is to explore the effects of various cushions on skin
      temperature and moisture at the body-seat interface during a 2-hour period of
      continuous sitting. Seventy-eight participants were randomly assigned to sit on
      one of the three types of wheelchair cushions for unrelieved sitting for over 2
      hours. Skin temperature and relative humidity (RH) were measured under the
      subjects' ischial tuberosities and thighs bilaterally with digital temperature
      and humidity sensors. Data were collected before sitting and at 15-minute
      intervals thereafter. Participants sitting on foam-fluid hybrid cushions showed
      significantly lower skin temperatures than those sitting on air-filled and foam
      cushions (p < 0.05), but RH did not differ significantly among the cushions (p =
      0.97). The three cushions produced a similar increasing trend in RH over time and
      RH reached a plateau during the 2-hour sitting period. To select the appropriate
      wheelchair cushion, the microclimate (heat and moisture control) between the body
      seat interface should be considered as well as pressure distribution. In
      comparison with foam-fluid hybrid cushions, the air-filled rubber and foam
      cushions tended to increase skin temperature by several degrees after prolonged
      sitting. However, cushion materials did not have significant differences in
      moisture accumulations.

PMID- 27689688
TI  - A Randomized Controlled Trial to Increase Navy Bean or Rice Bran Consumption in
      Colorectal Cancer Survivors.
AB  - Consumption of navy beans (NB) and rice bran (RB) have been shown to inhibit
      colon carcinogenesis. Given the overall poor diet quality in colorectal cancer
      (CRC) survivors and low reported intake of whole grains and legumes, practical
      strategies to increase consumption merit attention. This study determined
      feasibility of increasing NB or RB intake in CRC survivors to increase dietary
      fiber and examined serum inflammatory biomarkers and telomere lengths. Twenty
      nine subjects completed a randomized controlled trial with foods that included
      cooked NB powder (35 g/day), heat-stabilized RB (30 g/day), or no additional
      ingredient. Fasting blood, food logs, and gastrointestinal health questionnaires
      were collected. The amount of NB or RB consumed equated to 4-9% of subjects'
      daily caloric intake and no major gastrointestinal issues were reported with
      increased consumption. Dietary fiber amounts increased in NB and RB groups at
      Weeks 2 and 4 compared to baseline and to control (P <= 0.01). Telomere length
      correlated with age and HDL cholesterol at baseline, and with improved serum
      amyloid A (SAA) levels at Week 4 (P <= 0.05). This study concludes feasibility of
      increased dietary NB and RB consumption to levels associated with CRC
      chemoprevention and warrants longer-term investigations with both foods in high
      risk populations that include cancer prevention and control outcomes.

PMID- 27689691
TI  - Effect of media composition on bioavailability and toxicity of silver and silver
      nanoparticles in fish intestinal cells (RTgutGC).
AB  - To understand conditions affecting bioavailability and toxicity of citrate-coated
      silver nanoparticles (cit-AgNP) and dissolved silver at the luminal enterocyte
      interface, we exposed rainbow trout (Oncorhynchus mykiss) gut cells (RTgutGC) in
      media of contrasting composition: two amino acid-containing media, one of which
      was supplemented with proteins, as can be expected during digestion; and two
      protein and amino acid-free media contrasting low and high chloride content, as
      can be expected in the lumen of fish adapting to freshwater or seawater,
      respectively. Dose-response curves were generated measuring cell metabolic
      activity, membrane and lysosome integrity over a period of 72 hours. Then,
      nontoxic doses were applied and total silver accumulation, metallothionein and
      glutathione reductase mRNA levels were determined. The presence of proteins
      stabilized cit-AgNP keeping them in suspension. Conversely, in protein-free
      media, cit-AgNP agglomerated and settled, resulting in higher cellular
      accumulation of silver and toxicity. Chloride concentrations in exposure media
      modulated the toxicity of AgNO3 but not of cit-AgNP. Moreover, while amino acid
      containing media are protective against AgNO3, likely due to the formation of
      thiolate complexes, they are only partially protective against cit-AgNP.
      Viability assays indicated that lysosomes are targets of cit-AgNP, supporting the
      hypothesis that cit-AgNP exert toxicity intracellularly. Metallothionein, a
      sensor of metal bioavailability, was induced by cit-AgNP in high chloride medium
      but not in low chloride medium, indicating that chloride might have a role in
      mobilizing silver from intercellular vesicles. Overall, this study shows that
      AgNP bioavailability and toxicity in the intestine is linked to its luminal
      content.

PMID- 27689692
TI  - Protective effect of Schizandrin B against damage of UVB irradiated skin cells
      depend on inhibition of inflammatory pathways.
AB  - Schizandrin B is extracted from Schisandra chinensis (Turcz.) Baill. This study
      evaluated the photoprotective effect of Schizandrin B on oxidative stress injury
      of the skin caused by UVB-irradiation and the molecular mechanism of the
      photoprotective effect of Schizandrin B, and we firstly found that Schizandrin B
      could block Cox-2, IL-6 and IL-18 signal pathway to protect damage of skin cells
      given by UVB-irradiation. In the research, we found that Schizandrin B can
      attenuate the UVB-induced toxicity on keratinocytes and dermal fibroblasts in
      human body, and can outstandingly eliminated intracellular ROS produced by UVB
      irradiation. These results demonstrate that Schizandrin B can regulate the
      function of decreasing intracellular SOD's activity and increasing the expression
      level of MDA in HaCaT cells result from the guidance of UVB, and it markedly
      reduced the production of inflammatory factors such as Cox-2, IL-6 or IL-18,
      decreased the expression level of MMP-1, and interdicted degradation process of
      collagens in UVB-radiated cells. Therefore, skin keratinocytes can be effectively
      protected from UVB-radiated damage by Schizandrin B, and UVB-irradiation caused
      inflammatory responses can be inhibited by attenuating process of ROS generating.

PMID- 27689693
TI  - Observation of residues in tissues of chickens exposed to low dietary
      concentrations of chloramphenicol.
AB  - To investigate potential residues in tissues arising from naturally occurring low
      levels of chloramphenicol in plant material, feeding studies were conducted with
      chickens. A common chicken feed was prepared containing 0, 10, 50 and 200 MUg kg
      1 chloramphenicol and levels were confirmed by LC-MS/MS. Four separate groups of
      broiler chickens, eight animals in each group, were fed all their 35-day life
      with this contaminated feed. They were allowed ad libitum access to this feed and
      fresh water. After slaughtering the chickens, the residues in muscle and liver
      tissues were determined using GC/MS-NCI method. No residues were detected in
      tissues of animals from groups fed with feed containing 0, 10 or 50 ug kg-1. Low
      chloramphenicol residual concentrations were observed in a few of the muscle
      samples obtained from the group of chickens fed with feed containing
      chloramphenicol in added concentration 200 ug kg-1. No residues were detected in
      the remaining samples of this group. These results indicate that when residues of
      chloramphenicol are detected it is in all probability through illegal use.

PMID- 27689694
TI  - Characterization of Two Monoclonal Antibodies That Recognize Linker Region and
      Carboxyl Terminal Domain of Coronavirus Nucleocapsid Protein.
AB  - The transmissible gastroenteritis virus (TGEV) nucleocapsid (N) protein plays
      important roles in the replication and translation of viral RNA. The present
      study provides the first description of two monoclonal antibodies (mAbs) (5E8 and
      3D7) directed against the TGEV N protein linker region (LKR) and carboxyl
      terminal domain (CTD). The mAbs 5E8 and 3D7 reacted with native N protein in
      western blotting and immunofluorescence assay (IFA). Two linear epitopes,
      189SVEQAVLAALKKLG202 and 246VTRFYGARSSSA257, located in the LKR and CTD of TGEV N
      protein, respectively, were identified after truncating the protein and applying
      a peptide scanning technique. Using mAb 5E8, we observed that the N protein was
      expressed in the cytoplasm during TGEV replication and that the protein could be
      immunoprecipitated from TGEV-infected PK-15 cells. The mAb 5E8 can be applied for
      different approaches to diagnosis of TGEV infection. In addition, the antibodies
      represent useful tools for investigating the antigenic properties of the N
      protein.

PMID- 27689696
TI  - High Resolution Mapping of Bactericidal Monoclonal Antibody Binding Epitopes on
      Staphylococcus aureus Antigen MntC.
AB  - The Staphylococcus aureus manganese transporter protein MntC is under
      investigation as a component of a prophylactic S.aureus vaccine. Passive
      immunization with monoclonal antibodies mAB 305-78-7 and mAB 305-101-8 produced
      using MntC was shown to significantly reduce S. aureus burden in an infant rat
      model of infection. Earlier interference mapping suggested that a total of 23
      monoclonal antibodies generated against MntC could be subdivided into three
      interference groups, representing three independent immunogenic regions. In the
      current work binding epitopes for selected representatives of each of these
      interference groups (mAB 305-72-5 - group 1, mAB 305-78-7 - group 2, and mAB 305
      101-8 - group 3) were mapped using Hydrogen-Deuterium Exchange Mass Spectrometry
      (DXMS). All of the identified epitopes are discontinuous, with binding surface
      formed by structural elements that are separated within the primary sequence of
      the protein but adjacent in the context of the three-dimensional structure. The
      approach was validated by co-crystallizing the Fab fragment of one of the
      antibodies (mAB 305-78-7) with MntC and solving the three-dimensional structure
      of the complex. X-ray results themselves and localization of the mAB 305-78-7
      epitope were further validated using antibody binding experiments with MntC
      variants containing substitutions of key amino acid residues. These results
      provided insight into the antigenic properties of MntC and how these properties
      may play a role in protecting the hostagainst S. aureus infection by preventing
      the capture and transport of Mn2+, a key element that the pathogen uses to evade
      host immunity.

PMID- 27689697
TI  - Mtu1-Mediated Thiouridine Formation of Mitochondrial tRNAs Is Required for
      Mitochondrial Translation and Is Involved in Reversible Infantile Liver Injury.
AB  - Reversible infantile liver failure (RILF) is a unique heritable liver disease
      characterized by acute liver failure followed by spontaneous recovery at an early
      stage of life. Genetic mutations in MTU1 have been identified in RILF patients.
      MTU1 is a mitochondrial enzyme that catalyzes the 2-thiolation of 5-taurinomethyl
      2-thiouridine (taum5s2U) found in the anticodon of a subset of mitochondrial
      tRNAs (mt-tRNAs). Although the genetic basis of RILF is clear, the molecular
      mechanism that drives the pathogenesis remains elusive. We here generated liver
      specific knockout of Mtu1 (Mtu1LKO) mice, which exhibited symptoms of liver
      injury characterized by hepatic inflammation and elevated levels of plasma
      lactate and AST. Mechanistically, Mtu1 deficiency resulted in a loss of 2
      thiolation in mt-tRNAs, which led to a marked impairment of mitochondrial
      translation. Consequently, Mtu1LKO mice exhibited severe disruption of
      mitochondrial membrane integrity and a broad decrease in respiratory complex
      activities in the hepatocytes. Interestingly, mitochondrial dysfunction induced
      signaling pathways related to mitochondrial proliferation and the suppression of
      oxidative stress. The present study demonstrates that Mtu1-dependent 2-thiolation
      of mt-tRNA is indispensable for mitochondrial translation and that Mtu1
      deficiency is a primary cause of RILF. In addition, Mtu1 deficiency is associated
      with multiple cytoprotective pathways that might prevent catastrophic liver
      failure and assist in the recovery from liver injury.

PMID- 27689695
TI  - Epigenetic regulation of glycosylation and the impact on chemo-resistance in
      breast and ovarian cancer.
AB  - Glycosylation is one of the most fundamental posttranslational modifications in
      cellular biology and has been shown to be epigenetically regulated. Understanding
      this process is important as epigenetic therapies such as those using DNA
      methyltransferase inhibitors are undergoing clinical trials for the treatment of
      ovarian and breast cancer. Previous work has demonstrated that altered
      glycosylation patterns are associated with aggressive disease in women presenting
      with breast and ovarian cancer. Moreover, the tumor microenvironment of hypoxia
      results in globally altered DNA methylation and is associated with aggressive
      cancer phenotypes and chemo-resistance, a feature integral to many cancers. There
      is sparse knowledge on the impact of these therapies on glycosylation. Moreover,
      little is known about the efficacy of DNA methyltransferase inhibitors in hypoxic
      tumors. In this review, we interrogate the impact that hypoxia and epigenetic
      regulation has on cancer cell glycosylation in relation to resultant tumor cell
      aggressiveness and chemo-resistance.

PMID- 27689698
TI  - Interacting Social Processes on Interconnected Networks.
AB  - We propose and study a model for the interplay between two different dynamical
      processes -one for opinion formation and the other for decision making- on two
      interconnected networks A and B. The opinion dynamics on network A corresponds to
      that of the M-model, where the state of each agent can take one of four possible
      values (S = -2,-1, 1, 2), describing its level of agreement on a given issue. The
      likelihood to become an extremist (S = +/-2) or a moderate (S = +/-1) is
      controlled by a reinforcement parameter r >= 0. The decision making dynamics on
      network B is akin to that of the Abrams-Strogatz model, where agents can be
      either in favor (S = +1) or against (S = -1) the issue. The probability that an
      agent changes its state is proportional to the fraction of neighbors that hold
      the opposite state raised to a power beta. Starting from a polarized case
      scenario in which all agents of network A hold positive orientations while all
      agents of network B have a negative orientation, we explore the conditions under
      which one of the dynamics prevails over the other, imposing its initial
      orientation. We find that, for a given value of beta, the two-network system
      reaches a consensus in the positive state (initial state of network A) when the
      reinforcement overcomes a crossover value r*(beta), while a negative consensus
      happens for r < r*(beta). In the r - beta phase space, the system displays a
      transition at a critical threshold betac, from a coexistence of both orientations
      for beta < betac to a dominance of one orientation for beta > betac. We develop
      an analytical mean-field approach that gives an insight into these regimes and
      shows that both dynamics are equivalent along the crossover line (r*, beta*).

PMID- 27689700
TI  - Opportunist Turns Allergen: Double Life of Pneumocystis jirovecii in Asthma.

PMID- 27689699
TI  - "A Baby Was an Added Burden": Predictors and Consequences of Unintended
      Pregnancies for Female Sex Workers in Mombasa, Kenya: A Mixed-Methods Study.
AB  - INTRODUCTION: Female sex workers (FSW) have high rates of unintended pregnancy,
      sexually transmitted infections including HIV, and other adverse sexual and
      reproductive health outcomes. Few services for FSWs include contraception. This
      mixed-methods study aimed to determine the rate, predictors and consequences of
      unintended pregnancy among FSWs in Mombasa, Kenya. METHODS: A prospective cohort
      study of non-pregnant FSWs was conducted. Quantitative data were collected
      quarterly, including a structured questionnaire and testing for pregnancy and
      HIV. Predictors of unintended pregnancy were investigated using multivariate
      logistic regression. Qualitative data were gathered through focus group
      discussions and in-depth interviews with FSWs who became pregnant during the
      study, and interviews with five key informants. These data were transcribed,
      translated and analysed thematically. RESULTS: Four hundred women were enrolled,
      with 92% remaining in the cohort after one year. Fifty-seven percent reported
      using a modern contraceptive method (including condoms when used consistently).
      Over one-third (36%) of women were using condoms inconsistently without another
      method. Twenty-four percent had an unintended pregnancy during the study. Younger
      age, having an emotional partner and using traditional or no contraception, or
      condoms only, were independent predictors of unintended pregnancy. Women
      attributed pregnancy to forgetting to use contraception and being pressured not
      to by clients and emotional partners, as well as "bad luck". They described
      numerous negative consequences of unintended pregnancy. CONCLUSION: Modern
      contraceptive uptake is surprisingly low in this at-risk population, which in
      turn has a high rate of unintended pregnancy. The latter may result in financial
      hardship, social stigma, risk of abandonment, or dangerous abortion practices.
      FSWs face considerable barriers to the adoption of dual method contraceptive use,
      including low levels of control in their emotional and commercial relationships.
      Reproductive health services need to be incorporated into programs for sexually
      transmitted infections and HIV, which address the socially-determined barriers to
      contraceptive use.

PMID- 27689701
TI  - Muscle Regeneration after Critical Illness: Are Satellite Cells the Answer?

PMID- 27689702
TI  - Advancing a Third Revolution in Critical Care.

PMID- 27689703
TI  - Of Pigs, Mice, and Men: Understanding Early Triggers of Cystic Fibrosis Lung
      Disease.

PMID- 27689704
TI  - Physical Activity and Air Pollution Exposures in the Urban Environment.

PMID- 27689705
TI  - The HIPPO-Thesis of Pulmonary HYPERtension.

PMID- 27689706
TI  - Genome-Wide Association Studies in Obstructive Sleep Apnea. Will We Catch a Black
      Cat in a Dark Room?

PMID- 27689708
TI  - Who Says There Is No "I" in Team? Achieving Individual Success in Collaborative
      Clinical Research in Critical Care.

PMID- 27689707
TI  - Executive Summary of the American Heart Association and American Thoracic Society
      Joint Guidelines for Pediatric Pulmonary Hypertension.
AB  - Although pulmonary hypertension (PH) contributes significantly to poor outcomes
      in diverse pediatric diseases, approaches toward the care of children with PH
      have been limited by the lack of consensus guidelines from experts in the field.
      In a joint effort from the American Heart Association and American Thoracic
      Society, a committee of experienced clinicians was formed to systematically
      identify, synthesize, and appraise relevant evidence and then to formulate
      evidence-based recommendations regarding the diagnosis and management of
      pediatric PH. This brief report is an executive summary of the officially
      approved guidelines developed by the committee, highlighting a few key
      recommendations regarding the care of children with PH. Guidelines and the
      rationale for grading the strength of each recommendation are included in the
      online supplement.

PMID- 27689709
TI  - The Effect of Colonization with Potentially Pathogenic Microorganisms on
      Efferocytosis in Chronic Obstructive Pulmonary Disease.

PMID- 27689710
TI  - Continuous Positive Airway Pressure and Weight Gain: Do We Know the Mechanisms?

PMID- 27689711
TI  - Reply: Continuous Positive Airway Pressure and Weight Gain: Do We Know the
      Mechanisms?

PMID- 27689712
TI  - Lung Deflation and Cardiac Volumes: Not a Simple Relationship.

PMID- 27689713
TI  - How to Prepare for an Emergency or Disaster When You Have Lung Disease or a Sleep
      Disorder.

PMID- 27689714
TI  - Novel Covariance-Based Neutrality Test of Time-Series Data Reveals Asymmetries in
      Ecological and Economic Systems.
AB  - Systems as diverse as the interacting species in a community, alleles at a
      genetic locus, and companies in a market are characterized by competition (over
      resources, space, capital, etc) and adaptation. Neutral theory, built around the
      hypothesis that individual performance is independent of group membership, has
      found utility across the disciplines of ecology, population genetics, and
      economics, both because of the success of the neutral hypothesis in predicting
      system properties and because deviations from these predictions provide
      information about the underlying dynamics. However, most tests of neutrality are
      weak, based on static system properties such as species-abundance distributions
      or the number of singletons in a sample. Time-series data provide a window onto a
      system's dynamics, and should furnish tests of the neutral hypothesis that are
      more powerful to detect deviations from neutrality and more informative about to
      the type of competitive asymmetry that drives the deviation. Here, we present a
      neutrality test for time-series data. We apply this test to several microbial
      time-series and financial time-series and find that most of these systems are not
      neutral. Our test isolates the covariance structure of neutral competition, thus
      facilitating further exploration of the nature of asymmetry in the covariance
      structure of competitive systems. Much like neutrality tests from population
      genetics that use relative abundance distributions have enabled researchers to
      scan entire genomes for genes under selection, we anticipate our time-series test
      will be useful for quick significance tests of neutrality across a range of
      ecological, economic, and sociological systems for which time-series data are
      available. Future work can use our test to categorize and compare the dynamic
      fingerprints of particular competitive asymmetries (frequency dependence,
      volatility smiles, etc) to improve forecasting and management of complex adaptive
      systems.

PMID- 27689716
TI  - Avoidance of bottles during the establishment of breast feeds in preterm infants.
AB  - BACKGROUND: Preterm infants start milk feeds by gavage tube. As they mature,
      sucking feeds are gradually introduced. Women who choose to breast feed their
      preterm infant are not always able to be in hospital with their baby and need an
      alternative approach to feeding. Most commonly, milk (expressed breast milk or
      formula) is given by bottle. Whether using bottles during establishment of breast
      feeds is detrimental to breast feeding success is a topic of ongoing debate.
      OBJECTIVES: To identify the effects of avoidance of bottle feeds during
      establishment of breast feeding on the likelihood of successful breast feeding,
      and to assess the safety of alternatives to bottle feeds. SEARCH METHODS: We used
      the standard search strategy of the Cochrane Neonatal Review Group to search the
      Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE
      via PubMed (1966 to July 2016), Embase (1980 to July 2016) and CINAHL (1982 to
      July 2016). We also searched databases of clinical trials and the reference lists
      of retrieved articles for randomised controlled trials and quasi-randomised
      trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials
      comparing avoidance of bottles with use of bottles in women who have chosen to
      breast feed their preterm infant. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trial quality and extracted data. When
      appropriate, we contacted study authors for additional information. Review
      authors used standard methods of The Cochrane Collaboration and the Cochrane
      Neonatal Review Group. MAIN RESULTS: We included seven trials with 1152 preterm
      infants. Five studies used a cup feeding strategy, one used a tube feeding
      strategy and one used a novel teat when supplements to breast feeds were needed.
      We included the novel teat study in this review, as the teat was designed to more
      closely mimic the sucking action of breast feeding. The trials were of small to
      moderate size, and two had high risk of attrition bias. Adherence with cup
      feeding was poor in one of the studies, indicating dissatisfaction with this
      method by staff and/or parents; the remaining four cup feeding studies provided
      no such reports of dissatisfaction or low adherence. Meta-analyses provided
      evidence of low to moderate quality indicating that avoiding bottles increases
      the extent of breast feeding on discharge home (full breast feeding typical risk
      ratio (RR) 1.47, 95% confidence interval (CI) 1.19 to 1.80; any breast feeding RR
      1.11, 95% CI 1.06 to 1.16). Limited available evidence for three months and six
      months post discharge shows that avoiding bottles increases the occurrence of
      full breast feeding and any breast feeding at discharge and at six months post
      discharge, and of full (but not any) breast feeding at three months post
      discharge. This effect was evident at all time points for the tube alone strategy
      and for all except any breast feeding at three months post discharge for cup
      feeding. Investigators reported no clear benefit when the novel teat was used. No
      other benefits or harms were evident, including, in contrast to the previous
      (2008) review, length of hospital stay. AUTHORS' CONCLUSIONS: Evidence of low to
      moderate quality suggests that supplementing breast feeds by cup increases the
      extent and duration of breast feeding. Current insufficient evidence provides no
      basis for recommendations for a tube alone approach to supplementing breast
      feeds.

PMID- 27689715
TI  - Affective Disorders, Psychosis and Dementia in a Community Sample of Older Men
      with and without Parkinson's Disease.
AB  - BACKGROUND: Dementia and affective and psychotic symptoms are commonly associated
      with Parkinson's disease, but information about their prevalence and incidence in
      community representative samples remains sparse. METHODS: We recruited a
      community-representative sample 38173 older men aged 65-85 years in 1996 and used
      data linkage to ascertain the presence of PD, affective disorders, psychotic
      disorders and dementia. Diagnoses followed the International Classification of
      Disease coding system. Age was recorded in years. Follow up data were available
      until December 2011. RESULTS: The mean age of participants was 72.5 years and 333
      men (0.9%) had PD at study entry. Affective and psychotic disorders and dementia
      were more frequent in men with than without PD (respective odds ratios: 6.3
      [95%CI = 4.7, 8.4]; 14.2 [95%CI = 8.4, 24.0] and 18.2 [95%CI = 13.4, 24.6]).
      Incidence rate ratios of affective and psychotic disorders were higher among men
      with than without PD, although ratios decreased with increasing age. The age
      adjusted hazard ratio (HR) of an affective episode associated with PD was 5.0
      (95%CI = 4.2, 5.9). PD was associated with an age-adjusted HR of 8.6 (95%CI =
      6.1, 12.0) for psychotic disorders and 6.1 (95%CI = 5.5, 6.8) for dementia. PD
      and dementia increased the HR of depressive and psychotic disorders. CONCLUSIONS:
      PD increases the risk of affective and psychotic disorders, as well as dementia,
      among community dwelling older men. The risk of a recorded diagnosis of affective
      and psychotic disorders decreases with increasing age.

PMID- 27689717
TI  - Phase i trials in melanoma: A framework to translate preclinical findings to the
      clinic.
AB  - BACKGROUND: One of major issues in clinical trials in oncology is their high
      failure rate, despite the fact that the trials were designed based on the data
      from successful equivalent preclinical studies. This is in part due to the
      intrinsic homogeneity of preclinical model systems and the contrasting
      heterogeneity of actual patient responses. METHODS: We present a mathematical
      model-driven framework, phase i (virtual/imaginary) trials, that integrates the
      heterogeneity of actual patient responses and preclinical studies through a
      cohort of virtual patients. The framework includes an experimentally calibrated
      mathematical model, a cohort of heterogeneous virtual patients, an assessment of
      stratification factors, and treatment optimisation. We show the detailed process
      through the lens of melanoma combination therapy (chemotherapy and an AKT
      inhibitor), using both preclinical and clinical data. RESULTS: The mathematical
      model predicts melanoma treatment response and resistance to mono and combination
      therapies and was calibrated and then validated with in vitro experimental data.
      The validated model and a genetic algorithm were used to generate virtual
      patients whose tumour volume responses to the combination therapy matched
      statistically the actual heterogeneous patient responses in the clinical trial.
      Analyses on simulated cohorts revealed key model parameters such as a tumour
      volume doubling rate and a therapy-induced phenotypic switch rate that may have
      clinical correlates. Finally, our approach predicts optimal AKT inhibitor
      scheduling suggesting more effective but less toxic treatment strategies.
      CONCLUSION: Our proposed computational framework to implement phase i trials in
      cancer can readily capture observed heterogeneous clinical outcomes and predict
      patient survival. Importantly, phase i trials can be used to optimise future
      clinical trial design.

PMID- 27689718
TI  - Predicting the Dynamics and Heterogeneity of Genomic DNA Content within Bacterial
      Populations across Variable Growth Regimes.
AB  - For many applications in microbial synthetic biology, optimizing a desired
      function requires careful tuning of the degree to which various genes are
      expressed. One challenge for predicting such effects or interpreting typical
      characterization experiments is that in bacteria such as E. coli, genome copy
      number varies widely across different phases and rates of growth, which also
      impacts how and when genes are expressed from different loci. While such
      phenomena are relatively well-understood at a mechanistic level, our quantitative
      understanding of such processes is essentially limited to ideal exponential
      growth. In contrast, common experimental phenomena such as growth on
      heterogeneous media, metabolic adaptation, and oxygen restriction all cause
      substantial deviations from ideal exponential growth, particularly as cultures
      approach the higher densities at which industrial biomanufacturing and even
      routine screening experiments are conducted. To meet the need for predicting and
      explaining how gene dosage impacts cellular functions outside of exponential
      growth, we here report a novel modeling strategy that leverages agent-based
      simulation and high performance computing to robustly predict the dynamics and
      heterogeneity of genomic DNA content within bacterial populations across variable
      growth regimes. We show that by feeding routine experimental data, such as
      optical density time series, into our heterogeneous multiphasic growth simulator,
      we can predict genomic DNA distributions over a range of nonexponential growth
      conditions. This modeling strategy provides an important advance in the ability
      of synthetic biologists to evaluate the role of genomic DNA content and
      heterogeneity in affecting the performance of existing or engineered microbial
      functions.

PMID- 27689720
TI  - A versatile route to polymer-reinforced, broadband antireflective and
      superhydrophobic thin films without high-temperature treatment.
AB  - Broadband high transmittance, good mechanical robustness as well as simple and
      low temperature fabrication are three important aspects that dictate the
      practical applications of superhydrophobic thin films, especially on organic
      substrates. However, it has proved difficult to meet these challenges. In the
      present work, superhydrophobic thin films were prepared by first dip-coating
      solid silica nanoparticles, then spray-coating hollow silica nanoparticles,
      followed by spray-coating mesoporous silica nanosheets & poly(vinyl alcohol)
      (PVA), and eventually chemical vapor deposition of 1H,1H,2H,2H
      perflurooctyltriethoxysilane (POTS) at 90 degrees C. The optimized thin film has
      a maximum transmittance of 96.0% in the wavelength range of 300-2500nm and a WCA
      of 164 degrees  and a RA of 1 degrees . The thin film also shows good mechanical
      robustness toward water droplet impact test, sand impact abrasion test and tape
      adhesion tests, which results from PVA as a binder, the formation of covalent
      bond between the hydroxyl group of PVA and the ethoxy group of POTS and the
      chemical inertness of CC, CF bonds of POTS molecules. To our best knowledge, it
      is the first example where antireflective and superhydrophobic thin films of
      excellent mechanical robustness were realized at low temperature on organic
      substrates (PMMA, PC). The current work would provide a promising route to meet
      the challenges in practical applications simultaneously posed by the requirements
      of broadband antireflection, good mechanical robustness as well as simple and low
      temperature fabrication of superhydrophobic thin films.

PMID- 27689719
TI  - Bile acid profiles in diabetic (db/db) mice and their wild type littermates.
AB  - This study aimed to obtain information on bile acid profiles in diabetic (db/db)
      mice and their wild type (wt) littermates for the understanding of pathogenesis
      and discovery of potential biomarkers of type 2 diabetes. Analytical methods
      based on protein precipitation or solid-phase extraction together with liquid
      chromatography-tandem mass spectrometry were developed for the determination of
      25 bile acids in plasma, urine and feces samples collected from db/db and wt
      mice. GLP-1 concentration and hepatic genes related to bile acid synthesis were
      also investigated. The results showed that the concentrations of individual bile
      acids varied notably both interindividually and temporally. However, plasma,
      urine and feces samples displayed discriminating bile acid profiles between the
      db/db and wt groups, with the plasma profile showing the best differentiation
      capacity. In plasma and urine, the concentration variation of taurine-conjugated
      bile acids was more correlated with that of other taurine-conjugated bile acids,
      and vice versa for the unconjugated bile acids. Transcription of hepatic gene
      Cyp7b1 was downregulated, and Hsd3b7 upregulated in db/db mice. In conclusion,
      the bile acid profile, particularly that in plasma, can distinguish the two
      animal groups and is a promising biomarker for type 2 diabetes.

PMID- 27689721
TI  - Facile synthesis, structure and enhanced photocatalytic activity of novel
      BiOBr/Bi(C2O4)OH composite photocatalysts.
AB  - Novel composite photocatalysts BiOBr/Bi(C2O4)OH were successfully fabricated via
      a chemical etching method. After flower-like Bi(C2O4)OH microstructure assembled
      by nanorods was etched by KBr under an appropriate acidic condition, BiOBr nano
      rods could be in-situ generated in nanorods, forming a heterostructure. The
      heterostructures exhibited a commendable photocatalytic performance toward the
      degradation of rhodamine B under the visible light irradiation. The effective
      separation and transfer of the photogenerated electrons and holes were believed
      to be the main factor for the enhanced activity, which resulted from the
      intrinsic characteristic of p-n junction. The responsible mechanism was
      detailedly discussed, and the photogenerated holes and O2- radicals were
      confirmed to be the main active species for the photodegradation of RhB.

PMID- 27689722
TI  - Microfluidic synthesis of Ag@Cu2O core-shell nanoparticles with enhanced
      photocatalytic activity.
AB  - A microfluidic-based method for the continuous synthesis of Ag@Cu2O core-shell
      nanoparticles (NPs) has been developed. It only took 32s to obtain Ag@Cu2O core
      shell NPs, indicating a high efficiency of this microfluidic-based method.
      Triangular Ag nanoprisms were employed as the cores for the overgrowth of Cu2O
      through the reduction of Cu(OH)42- with ascorbic acid. The as-synthesized samples
      were characterized by XRD, TEM, SEM, HAADF-STEM, EDX, HRTEM, UV-vis spectra and
      N2 adsorption-desorption. The characterization results revealed that the as
      synthesized Ag@Cu2O core-shell NPs exhibited a well-defined core-shell
      nanostructure with a polycrystalline shell, which was composed of numbers of Cu2O
      domains epitaxially growing on the triangular Ag nanoprism. It was concluded that
      the synthesis parameters such as the molar ratio of trisodium citrate to AgNO3,
      H2O2 to AgNO3, NaOH to CuSO4, ascorbic acid to CuSO4 and AgNO3 to CuSO4 had
      significant effect on the synthesis of Ag@Cu2O core-shell NPs. Moreover, Ag@Cu2O
      core-shell NPs exhibited superior catalytic activity in comparison with pristine
      Cu2O NPs towards the visible light-driven degradation of methyl orange. This
      enhanced photocatalytic activity of Ag@Cu2O core-shell NPs was attributed to the
      larger BET surface area and improved charge separation efficiency. The trapping
      experiment indicated that holes and superoxide anion radicals were the major
      reactive species in the photodegradation of methyl orange over Ag@Cu2O core-shell
      NPs. In addition, Ag@Cu2O core-shell NPs showed no obvious deactivation in the
      cyclic test.

PMID- 27689723
TI  - Population Size, Growth, and Environmental Justice Near Oil and Gas Wells in
      Colorado.
AB  - We evaluated population size and factors influencing environmental justice near
      oil and gas (O&G) wells. We mapped nearest O&G well to residential properties to
      evaluate population size, temporal relationships between housing and O&G
      development, and 2012 housing market value distributions in three major Colorado
      O&G basins. We reviewed land use, building, real estate, and state O&G
      regulations to evaluate distributive and participatory justice. We found that by
      2012 at least 378,000 Coloradans lived within 1 mile of an active O&G well, and
      this population was growing at a faster rate than the overall population. In the
      Denver Julesburg and San Juan basins, which experienced substantial O&G
      development prior to 2000, we observed a larger proportion of lower value homes
      within 500 feet of an O&G well and that most O&G wells predated houses. In the
      Piceance Basin, which had not experienced substantial prior O&G development, we
      observed a larger proportion of high value homes within 500 feet of an O&G well
      and that most houses predated O&G wells. We observed economic, rural,
      participatory, and/or distributive injustices that could contribute to health
      risk vulnerabilities in populations near O&G wells. We encourage policy makers to
      consider measures to reduce these injustices.

PMID- 27689724
TI  - Design, synthesis and biological evaluation of novel 2,3-dihydroquinazolin- 4(1H)
      one derivatives as potential fXa inhibitors.
AB  - Coagulation factor Xa (fXa) is a particularly attractive target for the
      development of effective and safe anticoagulants. In this study, novel 2,3
      dihydroquinazolin-4(1H)-one derivatives were designed as potential fXa inhibitors
      based on anthranilamide structure which has been reported in our previous
      research. The experimental data showed that most of the designed compounds
      exhibited significant in vitro potency against fXa. Among them, compound 8e
      displayed the strongest potency against fXa with the IC50 value of 21 nM and
      highly selectivity versus thrombin (IC50 = 67 MUM) and excellent in vitro
      antithrombotic activity with its 2 * PT value of 1.2 MUM and 2 * aPTT value of
      0.6 MUM. In addition, 8e also displayed excellent in vivo antithrombotic activity
      in the rat arteriovenous shunt (AV-SHUNT) model. The bleeding risk evaluation
      showed that 8e had a similar safety profile as that of betrixaban. All results
      demonstrated that compound 8e could be considered as a potential fXa inhibitor
      for the prevention and treatment of thromboembolic diseases.

PMID- 27689725
TI  - Synthesis, in vitro evaluation and molecular docking studies of novel triazine
      triazole derivatives as potential alpha-glucosidase inhibitors.
AB  - A novel series of triazine-triazole derivatives 7a-7m were synthesized,
      characterized by 1H NMR and evaluated for their alpha-glucosidase inhibitory
      activity. All the synthesized compounds displayed potent alpha-glucosidase
      inhibitory activity with IC50 range of 11.63 +/- 0.15 to 37.44 +/- 0.35 MUM, when
      compared to the standard drug acarbose (IC50 = 817.38 +/- 6.27 MUM). Among the
      series, compound 7i (IC50 = 11.63 +/- 0.15 MUM) bearing 2,5-dichloro substitution
      at phenyl ring, represented the most potent alpha-glucosidase inhibitory
      activity. Molecular docking studies of the most active compounds with the
      homology modelled alpha-glucosidase were also performed to explore the possible
      inhibitory mechanism. Our studies shown that these triazine-triazole derivatives
      are a new class of alpha-glucosidase inhibitors.

PMID- 27689726
TI  - Repurposing N,N'-bis-(arylamidino)-1,4-piperazinedicarboxamidines: An unexpected
      class of potent inhibitors of cholinesterases.
AB  - Drug repurposing (=drug repositioning) is an effective way to cut costs for the
      development of new therapeutics and to reduce the time-to-market time-span.
      Following this concept a small library of compounds was screened for their
      ability to act as inhibitors of acetyl- and butyrylcholinesterase. Picloxydine,
      an established antiseptic, was shown to be an inhibitor for both enzymes.
      Systematic variation of the aryl substituents led to analogs possessing almost
      the same good properties as gold standard galantamine hydrobromide.

PMID- 27689727
TI  - Synthesis, biological evaluation and molecular modeling of 1-oxa-4-thiaspiro- and
      1,4-dithiaspiro[4.5]decane derivatives as potent and selective 5-HT1A receptor
      agonists.
AB  - Recently, 1-(1,4-dioxaspiro[4,5]dec-2-ylmethyl)-4-(2-methoxyphenyl)piperazine (1)
      was reported as a potent 5-HT1AR agonist with a moderate 5-HT1AR selectivity. In
      an extension of this work a series of derivatives of 1, obtained by combining
      different heterocyclic rings with a more flexible amine chain, was synthesized
      and tested for binding affinity and activity at 5-HT1AR and alpha1 adrenoceptors.
      The results led to the identification of 14 and 15 as novel 5-HT1AR partial
      agonists, the first being outstanding for selectivity (5-HT1A/alpha1d = 80), the
      latter for potency (pD2 = 9.58) and efficacy (Emax = 74%). Theoretical studies of
      ADME properties shows a good profile for the entire series and MDCKII-MDR1 cells
      permeability data predict a good BBB permeability of compound 15, which possess a
      promising neuroprotective activity. Furthermore, in mouse formalin test, compound
      15 shows a potent antinociceptive activity suggesting a new strategy for pain
      control.

PMID- 27689728
TI  - Piperlongumine (piplartine) and analogues: Antiproliferative microtubule
      destabilising agents.
AB  - Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving
      intense interest due to its antiproliferative and anticancer activities. We
      investigated the effects of 1 on tubulin and microtubules. Using both an isolated
      tubulin assay, and a combination of sedimentation and western blotting, we
      demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed
      by immunofluorescence and confocal microscopy, which showed that microtubules in
      MCF-7 breast cancer cells were depolymerized when treated with 1. We synthesised
      a number of analogues of 1 to explore structure-activity relationships. Compound
      13 had the best cytotoxic profile of this series, showing potent effects in human
      breast carcinoma MCF-7 cells whilst being relatively non-toxic to non-tumorigenic
      MCF-10a cells. These compounds will be further developed as potential clinical
      candidates for the treatment of breast cancer.

PMID- 27689729
TI  - Natural and synthetic bioactive inhibitors of glycogen synthase kinase.
AB  - Glycogen synthase kinase-3 is a multi-functional serine-threonine kinase and is
      involved in diverse physiological processes, including metabolism, cell cycle,
      and gene expression by regulating a wide variety of known substrates like
      glycogen synthase, tau-protein and beta-catenin. Aberrant GSK-3 has been involved
      in diabetes, inflammation, cancer, Alzheimer's and bipolar disorder. In this
      review, we present an overview of the involvement of GSK-3 in various signalling
      pathways, resulting in a number of adverse pathologies due to its dysregulation.
      In addition, a detailed description of the small molecule inhibitors of GSK-3
      with different mode of action discovered or specifically developed for GSK-3 has
      been presented. Furthermore, some clues for the future optimization of these
      promising molecules to develop specific drugs inhibiting GSK-3, for the treatment
      of associated disease conditions have also been discussed.

PMID- 27689730
TI  - Development of resveratrol-curcumin hybrids as potential therapeutic agents for
      inflammatory lung diseases.
AB  - Acute lung injury (ALI) is a major cause of acute respiratory failure in
      critically-ill patients. Resveratrol and curcumin are proven to have potent anti
      inflammatory efficacy, but their clinical application is limited by their
      metabolic instability. Here, a series of resveratrol and the Mono-carbonyl
      analogs of curcumin (MCAs) hybrids were designed and synthesized by efficient
      aldol construction strategy, and then screened for anti-inflammatory activities
      in vitro and in vivo. The results showed that the majority of analogs effectively
      inhibited the LPS-induced production of IL-6 and TNF-alpha. Five analogs, a9,
      a18, a19, a20 and a24 exhibited excellent anti-inflammatory activity in a dose
      dependent manner along with low toxicity in vitro. Structure activity
      relationship study revealed that the electron-withdrawing groups at meta-position
      and methoxyl group (OCH3) at the para position of the phenyl ring were important
      for anti-inflammatory activities. The most promising compound a18 decreased LPS
      induced TNF-alpha, IL-6, IL-12, and IL-33 mRNA expression. Additionally, a18
      significantly protected against LPS-induced acute lung injury in the in vivo
      mouse model. The research of resveratrol and MCAs hybrids could bring insight
      into the treatment of inflammatory diseases and compound a18 may serve as a lead
      compound for the development of anti-ALI agents.

PMID- 27689731
TI  - Structure-activity relationships and optimization of acyclic acylphloroglucinol
      analogues as novel antimicrobial agents.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to
      global public health, because it exhibits resistance to existing antibiotics and
      therefore high rates of morbidity and mortality. In this study, twenty-one
      natural product-based acylphloroglucinol congeners were synthesized, which
      possessed different side chains. Antibacterial screening against MRSA strains
      revealed that acyl moiety tailoring is a prerequisite for the antibacterial
      activity. Moreover, the lipophilicity, rather than the magnitude of the
      hydrophobic acyl tail dominates variability in activity potency. Compound 11j was
      identified as a promising lead for the generation of new anti-MRSA drug
      development. It was discovered by optimization of the side chain length in light
      of the potency, the breadth of the antibacterial spectrum, the rate of
      bactericidal action, as well as the membrane selectivity. Compound 11j exerted
      profound in vitro antibacterial activity against the MRSA strain (JCSC 2172), and
      its MIC was 3-4 orders of magnitude lower than that of vancomycin. A preliminary
      mode of action study of compound 11j at the biophysical and morphology levels
      disclosed that the mechanism underlying its anti-MRSA activity included membrane
      depolarization and, to a lesser extent, membrane disruption and cell lysis.

PMID- 27689732
TI  - Linker-switch approach towards new ATP binding site inhibitors of DNA gyrase B.
AB  - Due to increasing emergence of bacterial resistance, compounds with new
      mechanisms of action are of paramount importance. One of modestly researched
      therapeutic targets in the field of antibacterial discovery is DNA gyrase B. In
      the present work we synthesized a focused library of potential DNA gyrase B
      inhibitors composed of two key pharmacophoric moieties linked by three types of
      sp3-rich linkers to obtain three structural classes of compounds. Using molecular
      docking, molecular dynamics and analysis of conserved waters in the binding site,
      we identified a favourable binding mode for piperidin-4-yl and 4-cyclohexyl
      pyrrole-2-carboxamides while predicting unfavourable interactions with the active
      site for piperazine pyrrole-2-carboxamides. Biological evaluation of prepared
      compounds on isolated enzyme DNA gyrase B confirmed our predictions and afforded
      multiple moderately potent inhibitors of DNA gyrase B. Namely trans-4-(4,5
      dibromo-1H-pyrrole-2-carboxamide)cyclohexyl)glycine and 4-(4-(3,4-dichloro-5
      methyl-1H-pyrrole-2-carboxamido)piperidin-1-yl)-4-oxobutanoic acid with an IC50
      value of 16 and 0.5 MUM respectively.

PMID- 27689734
TI  - Importance of 'meeting of the minds': patient-reported outcomes and MRI.

PMID- 27689733
TI  - Synthesis, evaluation, and CoMFA study of fluoroquinophenoxazine derivatives as
      bacterial topoisomerase IA inhibitors.
AB  - New antibacterial agents with novel target and mechanism of action are urgently
      needed to combat problematic bacterial infections and mounting antibiotic
      resistances. Topoisomerase IA represents an attractive and underexplored
      antibacterial target, as such, there is a growing interest in developing
      selective and potent topoisomerase I inhibitors for antibacterial therapy. Based
      on our initial biological screening, fluoroquinophenoxazine 1 was discovered as a
      low micromolar inhibitor against E. coli topoisomerase IA. In the literature,
      fluoroquinophenoxazine analogs have been investigated as antibacterial and
      anticancer agents, however, their topoisomerase I inhibition was relatively
      underexplored and there is little structure-activity relationship (SAR)
      available. The good topoisomerase I inhibitory activity of 1 and the lack of SAR
      prompted us to design and synthesize a series of fluoroquinophenoxazine analogs
      to systematically evaluate the SAR and to probe the structural elements of the
      fluoroquinophenoxazine core toward topoisomerase I enzyme target recognition. In
      this study, a series of fluoroquinophenoxazine analogs was designed, synthesized,
      and evaluated as topoisomerase I inhibitors and antibacterial agents. Target
      based assays revealed that the fluoroquinophenoxazine derivatives with 9-NH2
      and/or 6-substituted amine functionalities generally exhibited good to excellent
      inhibitory activities against topoisomerase I with IC50s ranging from 0.24 to 3.9
      MUM. Notably, 11a bearing the 6-methylpiperazinyl and 9-amino motifs was
      identified as one of the most potent topoisomerase I inhibitors (IC50 = 0.48
      MUM), and showed broad spectrum antibacterial activity (MICs = 0.78-7.6 MUM)
      against all the bacteria strains tested. Compound 11g with the 6-bipiperidinyl
      lipophilic side chain exhibited the most potent antituberculosis activity (MIC =
      2.5 MUM, SI = 9.8). In addition, CoMFA analysis was performed to investigate the
      3D-QSAR of this class of fluoroquinophenoxazine derivatives. The constructed
      CoMFA model produced reasonable statistics (q2 = 0.688 and r2 = 0.806). The
      predictive power of the developed model was obtained using a test set of 7
      compounds, giving a predictive correlation coefficient r2pred of 0.767.
      Collectively, these promising data demonstrated that fluoroquinophenoxazine
      derivatives have the potential to be developed as a new chemotype of potent
      topoisomerase IA inhibitors with antibacterial therapeutic potential.

PMID- 27689736
TI  - Disease activity and left ventricular systolic function in rheumatoid arthritis.

PMID- 27689735
TI  - Baricitinib in patients with inadequate response or intolerance to conventional
      synthetic DMARDs: results from the RA-BUILD study.
AB  - BACKGROUND: Baricitinib is an oral, reversible, selective Janus kinase 1 and 2
      inhibitor. METHODS: In this phase III, double-blind 24-week study, 684 biologic
      disease-modifying antirheumatic drug (DMARD)-naive patients with rheumatoid
      arthritis and inadequate response or intolerance to >=1 conventional synthetic
      DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once
      daily, stratified by region and the presence of joint erosions. Endpoint measures
      included American College of Rheumatology 20% response (ACR20, primary endpoint),
      Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score
      <=3.3. RESULTS: More patients achieved ACR20 response at week 12 with baricitinib
      4 mg than with placebo (62% vs 39%, p<=0.001). Compared with placebo,
      statistically significant improvements in DAS28, SDAI remission, Health
      Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint
      pain and worst tiredness were observed. In a supportive analysis, radiographic
      progression of structural joint damage at week 24 was reduced with baricitinib
      versus placebo. Rates of adverse events during the treatment period and serious
      adverse events (SAEs), including serious infections, were similar among groups
      (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of
      tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma
      skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular
      events occurred (placebo). Baricitinib was associated with a decrease in
      neutrophils and increases in low-density and high-density lipoprotein.
      CONCLUSIONS: In patients with rheumatoid arthritis and an inadequate response or
      intolerance to conventional synthetic DMARDs, baricitinib was associated with
      clinical improvement and inhibition of progression of radiographic joint damage.
      TRIAL REGISTRATION NUMBER: NCT01721057; Results.

PMID- 27689737
TI  - Monocyte type I interferon signature in antiphospholipid syndrome is related to
      proinflammatory monocyte subsets, hydroxychloroquine and statin use.

PMID- 27689739
TI  - The influence of abscisic acid on the ethylene biosynthesis pathway in the
      functioning of the flower abscission zone in Lupinus luteus.
AB  - Flower abscission is a highly regulated developmental process activated in
      response to exogenous (e.g. changing environmental conditions) and endogenous
      stimuli (e.g. phytohormones). Ethylene (ET) and abscisic acid (ABA) are very
      effective stimulators of flower abortion in Lupinus luteus, which is a widely
      cultivated species in Poland, Australia and Mediterranean countries. In this
      paper, we show that artificial activation of abscission by flower removal caused
      an accumulation of ABA in the abscission zone (AZ). Moreover, the blocking of
      that phytohormone's biosynthesis by NDGA (nordihydroguaiaretic acid) decreased
      the number of abscised flowers. However, the application of NBD - an inhibitor of
      ET action - reversed the stimulatory effect of ABA on flower abscission,
      indicating that ABA itself is not sufficient to turn on the organ separation. Our
      analysis revealed that exogenous ABA significantly accelerated the
      transcriptional activity of the ET biosynthesis genes ACC synthase (LlACS) and
      oxidase (LlACO), and moreover, strongly increased the level of 1
      aminocyclopropane-1-carboxylic acid (ACC) - ET precursor, which was specifically
      localized within AZ cells. We cannot exclude the possibility that ABA mediates
      flower abscission processes by enhancing the ET biosynthesis rate. The findings
      of our study will contribute to the overall basic knowledge on the phytohormone
      regulated generative organs abscission in L. luteus.

PMID- 27689738
TI  - Salinity stress from the perspective of the energy-redox axis: Lessons from a
      marine intertidal flatworm.
AB  - In the context of global change, there is an urgent need for researchers in
      conservation physiology to understand the physiological mechanisms leading to the
      acquisition of stress acclimation phenotypes. Intertidal organisms continuously
      cope with drastic changes in their environmental conditions, making them
      outstanding models for the study of physiological acclimation. As the
      implementation of such processes usually comes at a high bioenergetic cost, a
      mitochondrial/oxidative stress approach emerges as the most relevant approach
      when seeking to analyze whole-animal responses. Here we use the intertidal
      flatworm Macrostomum lignano to analyze the bioenergetics of salinity acclimation
      and its consequences in terms of reactive oxygen/nitrogen species formation and
      physiological response to counteract redox imbalance. Measures of water fluxes
      and body volume suggest that M. lignano is a hyper-/iso-regulator. Higher
      salinities were revealed to be the most energetically expensive conditions, with
      an increase in mitochondrial density accompanied by increased respiration rates.
      Such modifications came at the price of enhanced superoxide anion production,
      likely associated with a high caspase 3 upregulation. These animals nevertheless
      managed to live at high levels of environmental salinity through the upregulation
      of several mitochondrial antioxidant enzymes such as superoxide dismutase.
      Contrarily, animals at low salinities decreased their respiration rates, reduced
      their activity and increased nitric oxide formation, suggesting a certain degree
      of metabolic arrest. A contradictory increase in dichlorofluorescein fluorescence
      and an upregulation of gluthathione-S-transferase pi 1 (GSTP1) expression were
      observed in these individuals. If animals at low salinity are indeed facing
      metabolic depression, the return to seawater may result in an oxidative burst. We
      hypothesize that this increase in GSTP1 could be a "preparation for oxidative
      stress", i.e. a mechanism to counteract the production of free radicals upon
      returning to seawater. The results of the present study shed new light on how
      tolerant organisms carry out subcellular adaptations to withstand environmental
      change.

PMID- 27689740
TI  - Synthesis, characterization, anti-bacterial, anti-fungal and nematicidal
      activities of 2-amino-3-cyanochromenes.
AB  - Soil-borne plant pathogens such as nematodes, fungi and some bacteria not only
      affect the plant cultures but also economy and environmental implications. As a
      result of these pathogens attacks, the yield and quality of crops is affected.
      Therefore, synthesis of new compounds to control these pathogens is very
      important and need of time. Chromenes are considered important group of
      heterocyclic compounds and exhibited significant biological activities. 2-amino-3
      cyano chromenes are considered important medicinal scaffolds among the chromenes.
      We describe three component microwave assisted synthesis of 2-amino-3-cyano
      chromenes. The versatility of the reaction was examined by varying the aldehydes
      in the reaction mixture which lead to the synthesis of series of 2-amino-3
      cyanochromenes (1-9). The structural elucidations of the compounds were studied
      by 1H NMR, 13C NMR, HRMS and FTIR spectrometer and results were well correlated.
      The synthesized compounds were evaluated for their anti-bacterial, anti-fungal
      and nematicidal activities. Among the synthesized compounds, compound 6 showed
      good anti-bacterial activity while compound 9 exhibited high anti-fungal
      activity. In case of nematicidal activity, compound 8 indicated high activity as
      compare with other compounds followed by compound 9. Results indicate that these
      synthesized compounds could be used as effective control for soil-borne plant
      pathogens such as nematodes, fungi and bacteria and can help to improve the plant
      production.

PMID- 27689741
TI  - Sapium sebiferum leaf extract mediated synthesis of palladium nanoparticles and
      in vitro investigation of their bacterial and photocatalytic activities.
AB  - There is a growing need to introduce eco-friendly and sustainable procedures for
      the synthesis of metal nanoparticles that include a mild reaction conditions,
      simple reaction setup, use of nontoxic medium such as water and plant extract,
      cost effectiveness as well as greater efficiency for biomedical and catalytic
      applications. For this purpose, small and highly dispersed palladium
      nanoparticles (PdNPs) were prepared by eco-friendly and cost effective green
      method using water soluble leaf extract of Sapium sebiferum as a reducing and
      capping agent. The formation of PdNPs was optimized at various temperatures i.e.
      (30 degrees C, 60 degrees C and 90 degrees C) and different leaves extract (5mL
      and 10mL) in order to control their size and shape. The results indicated that
      PdNPs synthesized at 10mL leaf extract concentration and 60 degrees C temperature
      have small sized (5nm) and spherical shape. The nanoparticles formation, their
      dispersion, size and shape were confirmed by various characterization techniques
      i.e. UV-Vis spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, X-ray
      diffraction (XRD), scanning electron microscopy (SEM), high resolution
      transmission electron microscopy (HRTEM), thermo gravimetric analysis (TGA) and
      Dynamic light scattering technique (DLS) analysis. The biologically synthesized
      PdNPs were tested for size dependent photo degradation of methylene blue and
      inactivation of bacteria. The PdNPs synthesized at optimized condition (10mL
      extract concentration and 60 degrees C) have strong photo catalytic activity and
      reduced 90% methylene blue in 70min. The optimized PdNPs also showed strong
      bacterial inhibition against Staphylococcus aureus 29(+/-0.8mm), Bacillus
      subtilis 19(+/-0.6mm) and pseudomonas aeruginosa 11(+/-0.6mm). The results of
      this examination demonstrate effective applications of extremely active PdNPs.

PMID- 27689742
TI  - Toxicity and efficacy of CdO nanostructures on the MDCK and Caki-2 cells.
AB  - This article reports the toxicological effects of synthesized cadmium oxide (CdO)
      nanostructures via a simple green route using a Polygala tenuifolia root extract
      on normal and renal tumor cells. First, the formation of cadmium oxide
      nanostructures were confirmed structurally by Fourier transform infrared
      spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy (XPS). The
      powder was crystallized in a cubic structure with a space group of Fm-3m. The
      mean crystallize size was approximately 40 and 44nm from the Scherrer and size
      strain plots, respectively. The surface states of the cadmium oxide nanostructure
      using the O 1s and Cd 3d spectra were analyzed by XPS. Transmission electron
      microscopy showed that the simple green route resulted in various morphologies of
      synthesized cadmium oxide, such as trigonal-, tetrahedron-, and sheet-like
      structures. Finally, the toxic effects of the cadmium oxide nanostructures on
      Madin-Darby canine kidney epithelial cells (MDCK cells), as well as the human
      renal cancer cell line (Caki-2 cells) were investigated using a SRB assay and two
      color flow cytometry analysis. The cadmium oxide nanostructures showed
      significant cell growth inhibition in normal and also tumor cells in a dose
      dependent manner. On the other hand, the inhibition was higher in the cancer
      cells compared to the normal cells.

PMID- 27689743
TI  - Impact of the double expression of MYC and BCL2 on outcomes of localized primary
      gastric diffuse large B-cell lymphoma patients in the rituximab era.

PMID- 27689744
TI  - Novel function of FAXDC2 in megakaryopoiesis.
AB  - FAXDC2 (fatty acid hydroxylase domain containing 2) is a member of the fatty acid
      hydroxylase superfamily. Given the important role of fatty acids in
      megakaryocytes, we have studied the role of this gene in the development of this
      lineage. Here we show that the expression of FAXDC2 is constantly elevated during
      megakaryocyte maturation. In contrast, FAXDC2 is significantly downregulated in
      acute myeloid leukemia and acute megakaryoblastic leukemia. Moreover, FAXDC2
      overexpression promotes the differentiation of megakaryocytic cell lines and
      primary cells, whereas its knockdown disrupts their maturation. Mechanism study
      shows that FAXDC2 overexpression enhances extracellular signal-regulated kinase
      (ERK) signaling and increases RUNX1 (Runt-related transcription factor 1)
      expression. FAXDC2 also restores megakaryocytic differentiation in cells exposed
      to an ERK inhibitor or those expressing a dominant negative form of RUNX1.
      Finally, FAXDC2 overexpression leads to an increase in sphingolipid GM3 synthase,
      suggesting a potential role of FAXDC2 in lipid metabolism that increases ERK
      signaling and facilitates megakaryocyte differentiation. Together, these results
      show that FAXDC2 plays a novel role in development of megakaryocytes and its
      dysregulation may contribute to abnormal hematopoietic cell development in
      leukemia.

PMID- 27689745
TI  - Palladium(II)-Catalyzed Enantioselective Reactions Using COP Catalysts.
AB  - Allylic amides, amines, and esters are key synthetic building blocks. Their
      enantioselective syntheses under mild conditions is a continuing pursuit of
      organic synthesis methods development. One opportunity for the synthesis of these
      building blocks is by functionalization of prochiral double bonds using
      palladium(II) catalysis. In these reactions, nucleopalladation mediated by a
      chiral palladium(II) catalyst generates a new heteroatom-substituted chiral
      center. However, reactions where nucleopalladation occurs with antarafacial
      stereoselectivity are difficult to render enantioselective because of the
      challenge of transferring chiral ligand information across the square-planar
      palladium complex to the incoming nucleophile. In this Account, we describe the
      development and use of enantiopure palladium(II) catalysts of the COP (chiral
      cobalt oxazoline palladacyclic) family for the synthesis of enantioenriched
      products from starting materials derived from prochiral allylic alcohols. We
      begin with initial studies aimed at rendering catalyzed [3,3]-sigmatropic
      rearrangements of allylic imidates enantioselective, which ultimately led to the
      identification of the significant utility of the COP family of Pd(II) catalysts.
      The first use of an enantioselective COP catalyst was reported by Richards' and
      our laboratories in 2003 for the enantioselective rearrangement of allylic N
      arylimidates. Shortly thereafter, we discovered that the chloride-bridged COP
      dimer, [COP-Cl]2, was an excellent enantioselective catalyst for the
      rearrangement of (E)-allylic trichloroacetimidates to enantioenriched allylic
      trichloroacetamides, this conversion being the most widely used of the allylic
      imidate rearrangements. We then turn to discuss SN2' reactions catalyzed by the
      acetate-bridged COP dimer, [COP-OAc]2, which proceed by a unique mechanism to
      provide branched allylic esters and allylic phenyl ethers in high
      enantioselectivity. Furthermore, because of the unique
      nucleopalladation/deoxypalladation mechanism of these SN2' reactions, they
      provide exclusively the branched allylic product. Importantly, both enantiomers
      of the [COP-Cl]2 and [COP-OAc]2 catalysts are commercially available. We also
      briefly consider several other enantioselective reactions catalyzed by COP
      complexes. The mechanism of enantioselective COP-catalyzed allylic rearrangements
      and allylic substitutions is discussed in some detail. In both reactions,
      nucleopalladation is found to be the enantiodetermining step. The cyclobutadienyl
      "floor" of the COP catalyst is critical for transmitting chiral information
      across the palladium square plane in these reactions. This structural feature
      enables high enantioselection to be realized in spite of the nearly 180 degrees 
      angle between the catalyst, electrophile and nucleophile in the
      enantiodetermining step. Our discussion concludes by considering several uses of
      the COP family of catalysts by other researchers for the enantioselective
      synthesis of biologically active chiral molecules. We anticipate that additional
      uses for COP catalysts will emerge in the future. In addition, the structural
      features of these catalysts that we have identified as important for achieving
      high enantioselection should be useful in the future development of improved
      enantioselective Pd(II) catalysts.

PMID- 27689746
TI  - Copper-Mediated C-N Coupling of Arylsilanes with Nitrogen Nucleophiles.
AB  - A method for the oxidative coupling of arylsilanes with nitrogen nucleophiles is
      reported. This method occurs with a broad range of heptamethyltrisiloxylarenes
      and nitrogen nucleophiles, proceeds with the arylsilane as limiting reagent, and
      does not require a fluoride activator with electron-poor arylsilanes. The
      combination of this method with C-H silylation generates arylamines from
      unactivated arenes with site selectivity controlled by steric effects. This
      combination of steps gives direct access to many compounds that cannot be
      accessed via alternative C-H functionalization methods, including direct C-H
      amination or the combination of C-H borylation and amination.

PMID- 27689747
TI  - Electrically Conductive Hierarchical Carbon Nanotube Networks with Tunable
      Mechanical Response.
AB  - Small diameter carbon nanotube (CNTs) are synthesized directly from a parent CNT
      forest using a floating catalyst chemical vapor deposition (CVD) method. To
      support a new CNT generation from an existing forest, an alumina coating was
      applied to the CNT forest using atomic layer deposition (ALD). The new generation
      of small diameter CNTs (8 nm average) surround the first generation, filling the
      interstitial regions. The hierarchical forests exhibit a 5-10-fold increase in
      stiffness, and the two generations are electrically addressable in spite of the
      interfacial alumina layer between them. This work enables the design of complex
      CNT architectures with hierarchical features that bring tailored properties such
      as high specific surface area and robust mechanical properties that can benefit a
      range of applications.

PMID- 27689750
TI  - Prolongation of kidney allograft survival regulated by indoleamine 2, 3
      dioxygenase in immature dendritic cells generated from recipient type bone marrow
      progenitors.
AB  - Immature dendritic cells (iDCs) are bone marrow-derived professional antigen
      presenting cells, exhibit very low levels of the co-stimulatory molecules CD80
      (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II
      and play a critical role in triggering antigen-specific immunotolerance. The
      enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism
      rate-limiting step enzyme. IDO secreted by DCs shows an association with the
      suppression of T-cell responses and promotion of tolerance. In this study, BN rat
      recipients were pre-injected with donor renal alloantigen-treated recipient iDCs
      before kidney transplantation. The renal allograft exhibited a lighter renal
      rejection response, prolonged graft survival time, and an increasing content of
      CD4+CD25+Foxp3+ regulatory T cells (Tregs). Additionally, up-regulated secretion
      of Th2 cytokines were found in recipient sera post-transplantation. Transfection
      of si-IDO1 RNA into renal-antigen-treated recipient iDCs reversed these changes,
      which suggested that IDO channel signaling may be involved in iDC-induced
      allograft immunotolerance. These results suggested that iDC-induced and IDO
      mediated allograft immunotolerance might be a potentially feasible tactic to
      prolong allograft survival, in addition to immunosuppressive drugs.

PMID- 27689749
TI  - Tuberculosis-sensitized monocytes sustain immune response of interleukin-37.
AB  - Roles of human IL-37 in infections remain poorly characterized. Although plasma
      IL-37 is elevated in patients with tuberculosis (TB), IL-37 source and immune
      correlate in TB have not been investigated. It is also unknown whether and how TB
      can influence the ability of immune cells to mount innate responses of IL-37 and
      pre-inflammatory cytokines. Here, we demonstrated that IL-37b-producing monocytes
      coincided with a source of elevated plasma IL-37b in TB patients. While IL-37b
      production in TB was associated with prolonged/complicated TB, TB burdens and
      inflammatory reactions, it negatively correlated with immune responses of pro
      inflammatory cytokines IL-1beta, IL-6 and TNF-alpha or IL-10. Interestingly,
      mycobacterial re-infection of monocytes from TB patients, but not healthy BCG
      vaccinated controls, enhanced or sustained IL-37b production by cultured
      monocytes. TB-sensitized monocytes from TB patients mounted more robust immune
      responses of IL-37b than those of pre-inflammatory cytokines during mycobacterial
      re-infection in culture. Our data represent new findings in terms of IL-37b
      responses, immune correlates and potential mechanisms in TB patients.

PMID- 27689751
TI  - Cholesterol-Based Grafted Polymer Brushes as Alignment Coating with Temperature
      Tuned Anchoring for Nematic Liquid Crystals.
AB  - Novel alignment coating with temperature-tuned anchoring for nematic liquid
      crystals (NLCs) was successfully fabricated in three step process, involving
      polymerization of poly(cholesteryl methacrylate) (PChMa) from oligoproxide
      grafted to the glass surface premodified with 3-aminopropyltriethoxysilane.
      Molecular composition, thickness, wettability of the PChMa coating and its
      alignment action for a NLC were examined with time of flight-secondary ion mass
      spectrometry, ellipsometry, contact angle measurements, polarization optical
      microscopy and commercially produced PolScope technique allowing for mapping of
      the optic axis and optical retardance within the microscope field view. We find
      that the PChMa coating provides a specific monotonous increase (decrease) in the
      tilt angle of the NLC director with respect to the substrates normal upon heating
      (cooling) referred to as anchoring tuning.

PMID- 27689748
TI  - Age-related changes in cerebellar and hypothalamic function accompany non
      microglial immune gene expression, altered synapse organization, and excitatory
      amino acid neurotransmission deficits.
AB  - We describe age-related molecular and neuronal changes that disrupt mobility or
      energy balance based on brain region and genetic background. Compared to young
      mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance)
      impairments. In contrast, aged BALB mice exhibit marked energy balance (but not
      locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene
      expression accompany these phenotypes. Aging evokes upregulation of immune
      pattern recognition receptors and cell adhesion molecules. However, these changes
      do not localize to microglia, the major CNS immunocyte. Consistent with a
      neuronal role, there is a marked age-related increase in excitatory synapses over
      the cerebellum and hypothalamus. Functional imaging of these regions is
      consistent with age-related synaptic impairments. These studies suggest that
      aging reactivates a developmental program employed during embryogenesis where
      immune molecules guide synapse formation and pruning. Renewed activity in this
      program may disrupt excitatory neurotransmission, causing significant behavioral
      deficits.

PMID- 27689752
TI  - Solvent and Heavy-Atom Effects on the O2(X3Sigmag-) -> O2(b1Sigmag+) Absorption
      Transition.
AB  - The effect of 16 liquid solvents on both the spectrum and molar absorption
      coefficient of the X3Sigmag- -> b1Sigmag+ transition in molecular oxygen has been
      examined. The ability to monitor this weak transition using air or oxygen
      saturated samples at atmospheric pressure was facilitated by the rapid and
      efficient O2(b1Sigmag+) -> O2(a1Deltag) transition, which allowed the use of
      O2(a1Deltag) phosphorescence as a sensitive probe of O2(b1Sigmag+) production.
      The results of these O2(a1Deltag) phosphorescence experiments are consistent with
      the results of independent experiments in which the O2(a1Deltag) thus produced
      was "trapped" via a chemical reaction. The data recorded were used to calculate
      rate constants for the O2(b1Sigmag+) -> O2(X3Sigmag-) radiative transition, a
      parameter that is otherwise difficult to directly obtain from such a wide range
      of solvents using O2(b1Sigmag+) -> O2(X3Sigmag-) phosphorescence. The data show
      that the response of the O2(b1Sigmag+) -> O2(X3Sigmag-) radiative transition to
      solvent is not the same as that of the O2(b1Sigmag+) -> O2(a1Deltag) and
      O2(a1Deltag) -> O2(X3Sigmag-) radiative transitions, both of which have been
      extensively examined over the years. However, our data are consistent with a
      theoretical model proposed by Minaev for the effect of solvent on radiative
      transitions in oxygen and, as such, arguably provide one of the final chapters in
      describing a system that has challenged the scientific community for years.

PMID- 27689753
TI  - Remote Substituent Effects on the Structures and Stabilities of P?E pi-Stabilized
      Diphosphatetrylenes (R2P)2E (E = Ge, Sn).
AB  - A rare P-E pi interaction between the lone pair of a planar P center and the
      vacant p orbital at the Ge or Sn center provides efficient stabilization for P
      substituted tetrylenes (R2P)2E (E = Ge, Sn) and enables isolation of the first
      example of a compound with a crystallographically authenticated P?Sn bond. Subtle
      changes in the electronic properties of the bulky aryl substituents in these
      compounds change the preference for planar versus pyramidal P centers in the
      solid state; however, variable-temperature NMR spectroscopy indicates that in
      solution these species are subject to a dynamic equilibrium, which interconverts
      the planar and pyramidal P centers. Consistent with this, density functional
      theory studies suggest that there is only a small energy difference between the
      planar and pyramidal forms of these compounds and reveal a small singlet-triplet
      energy separation, suggesting potentially interesting reactivities.

PMID- 27689754
TI  - Synergy between Experimental and Computational Chemistry Reveals the Mechanism of
      Decomposition of Nickel-Ketene Complexes.
AB  - A series of (dppf)Ni(ketene) complexes were synthesized and fully characterized.
      In the solid state, the complexes possess eta2-(C,O) coordination of the ketene
      in an overall planar configuration. They display similar structure in solution,
      except in some cases, the eta2-(C,C) coordination mode is also detected. A
      combination of kinetic analysis and DFT calculations reveals the complexes
      undergo thermal decomposition by isomerization from eta2-(C,O) to eta2-(C,C)
      followed by scission of the C?C bond, which is usually rate limiting and results
      in an intermediate carbonyl carbene complex. Subsequent rearrangement of the
      carbene ligand is rate limiting for electron poor and sterically large ketenes,
      and results in a carbonyl alkene complex. The alkene readily dissociates,
      affording alkenes and (dppf)Ni(CO)2. Computational modeling of the
      decarbonylation pathway with partial phosphine dissociation reveals the barrier
      is reduced significantly, explaining the instability of ketene complexes with
      monodentate phosphines.

PMID- 27689755
TI  - Different forms of alpha-1 antitrypsin and neutrophil activation mediated by
      human anti-PR3 IgG antibodies.
AB  - BACKGROUND: One of characteristic findings in granulomatosis with polyangiitis
      (GPA) is the presence of proteinase-3 (anti-PR3) specific antibodies. These
      antibodies can cause neutrophil activation, degranulation and generation of
      reactive oxygen species (ROS). Each of these inflammatory events can be
      suppressed by circulating alpha-1 antitrypsin (A1AT). A1AT is an acute phase
      protein increasing during inflammation, however, it may circulate as an inactive
      polymeric protein. The aim was to analyze how different types of A1AT can affect
      anti-PR3 mediated neutrophil activation. METHODS: Granulocytes were obtained from
      the blood of healthy volunteers and purified by density gradient centrifugation.
      Effects of A1AT on IgG anti-PR3-mediated neutrophil activation were evaluated by
      stimulation of the cells with native IgG anti-PR3 antibodies in the presence of
      native or polymerized A1AT. Analyses of selected proinflammatory genes expression
      were performed using quantitative real-time. Flow cytometry was used to study the
      cell membrane PR3, its binding by anti-PR3 IgG, and production of ROS at presence
      A1AT. Neutrophil elastase complexes with A1AT were measured by ELISA. RESULTS:
      Native A1AT inhibited formation of the immune complex of PR3 with anti-PR3 and
      anti-PR3-mediated neutrophil activation/ROS production. Protective effect of
      polymerized A1AT against these events was diminished at least fivefold.
      CONCLUSIONS: Native A1AT can prevent pivotal events of neutrophils' activation by
      anti-PR3 IgG, the main autoantibody in anti-PR3 dependent vasculitis. Inhibitory
      properties of polymerized A1AT, decreased plausibly due to a loss of anti
      protease function, can explain more severe course of the disease in subjects with
      deficiency of A1AT.

PMID- 27689756
TI  - Evaluation of antidepressant-like and anxiolytic-like activity of purinedione
      derivatives with affinity for adenosine A2A receptors in mice.
AB  - BACKGROUND: It has recently been suggested that the adenosine A2A receptor plays
      a role in several animal models of depression. Additionally, A2A antagonists have
      reversed behavioral deficits and exhibited a profile similar to classical
      antidepressants. METHODS: In the present study, imidazo- and pyrimido[2,1
      f]purinedione derivatives (KD 66, KD 167, KD 206) with affinity to A2A receptors
      but poor A1 affinity were evaluated for their antidepressant- and anxiolytic-like
      activity. The activity of these derivatives was tested using a tail suspension
      and forced swim test, two widely-used behavioral paradigms for the evaluation of
      antidepressant-like activity. In turn, the anxiolytic activity was evaluated
      using the four-plate test. RESULTS: The results showed the antidepressant-like
      activity of pyrimido- and imidazopurinedione derivatives (i.e. KD 66, KD 167 and
      KD 206) in acute and chronic behavioral tests in mice. KD 66 revealed an
      anxiolytic-like effect, while KD 167 increased anxiety behaviors. KD 206 had no
      effect on anxiety. Furthermore, none of the tested compounds increased locomotor
      activity. CONCLUSION: Available data support the proposition that the examined
      compounds with adenosine A2A receptor affinity may be an interesting target for
      the development of antidepressant and/or anxiolytic agents.

PMID- 27689758
TI  - TSCA 2.0: A New Era in Chemical Risk Management.

PMID- 27689759
TI  - Quantum Strong Coupling with Protein Vibrational Modes.
AB  - In quantum electrodynamics, matter can be hybridized to confined optical fields
      by a process known as light-matter strong coupling. This gives rise to new hybrid
      light-matter states and energy levels in the coupled material, leading to
      modified physical and chemical properties. Here, we report for the first time the
      strong coupling of vibrational modes of proteins with the vacuum field of a Fabry
      Perot mid-infrared cavity. For two model systems, poly(l-glutamic acid) and
      bovine serum albumin, strong coupling is confirmed by the anticrossing in the
      dispersion curve, the square root dependence on the concentration, and a vacuum
      Rabi splitting that is larger than the cavity and vibration line widths. These
      results demonstrate that strong coupling can be applied to the study of proteins
      with many possible applications including the elucidation of the role of
      vibrational dynamics in enzyme catalysis and in H/D exchange experiments.

PMID- 27689757
TI  - Mechanisms underlying the hyperalgesic responses triggered by joint activation of
      TLR4.
AB  - BACKGROUND: Toll-like receptors (TLRs) including TLR4 and their signal pathways
      contribute to the pathogenesis of arthritis. Herein, we evaluated the mechanisms
      underlying the hyperalgesic response caused by TLR4 activation in the tibio
      tarsal joint in mice. METHODS: Joint inflammatory hyperalgesia was induced by
      intra-articular (ia) injection of LPS (lipopolysaccharide- TLR4 agonist) in
      C57BL/6, TLR4, TLR2, MyD88, TRIF, TNFR1/2 and IL-1R1 knockout (-/-) mice. Joint
      hyperalgesia was evaluated using an electronic von Frey. Neutrophil recruitment
      was assessed by MPO activity. Joint levels of cytokines were measured by ELISA.
      RESULTS: Firstly, it was shown that LPS injected into the joints causes a dose-
      and time-dependent reduction in the mechanical nociceptive threshold. The TLR4
      activation in the joint triggers mechanical hyperalgesia and neutrophil
      migration, which was abolished in TLR4 -/- and MyD88-/-, but not in TLR2-/- and
      TRIF-/- mice. Besides, joint administration of LPS increased the release of TNF
      alpha, IL-1beta, and KC/CXCL1, which were reduced in TLR4-/- and MyD88-/-, but
      not in TRIF-/- mice. In agreement, the LPS-induced joint nociceptive effect was
      decreased in TNFR1/2-/- and IL-1R1-/- mice or in mice pre-treated with a CXCR1/2
      selective antagonist (DF2156A). CONCLUSIONS: These results suggest that TLR4
      activation in the joint produces articular hyperalgesia via MyD88 signaling
      pathway. Moreover, this pathway is involved in the cascade of events of articular
      hyperalgesia through mechanisms dependent on cytokines and chemokines production.
      Thus, TLR4/MyD88 signaling pathway inhibitors might be useful for the treatment
      of inflammatory joint pain.

PMID- 27689760
TI  - Complications, Readmissions, and Reoperations in Posterior Cervical Fusion.
AB  - STUDY DESIGN: Retrospective cohort study of the American College of Surgeons
      National Surgical Quality Improvement Program database from 2011 to 2012.
      OBJECTIVE: Minimizing the morbidity of posterior cervical fusion can be improved
      with identification of patient risk factors. SUMMARY OF BACKGROUND DATA:
      Posterior cervical fusion is an effective technique for treating a variety of
      pathology. Stability and neurological improvement have been well documented. The
      increasing frequency of these procedures necessitates further investigation into
      the factors that may negatively impact perioperative care. METHODS: The American
      College of Surgeons National Surgical Quality Improvement Program was queried for
      all patients undergoing posterior cervical fusion in 2011 and 2012. Preoperative
      and intraoperative variables were investigated for correlation to complications,
      readmissions, prolonged intubation, reintubation, and reoperation. A frailty
      based score was used to assess preoperative risk. Regression models for
      prediction were performed. RESULTS: The study identified 5627 patients of
      posterior cervical fusion in 2011 and 2012. Of these, 2029 patients (36.1%) had
      any of our identified complications. Transfusion was the most common in 1482
      (26.3%) patients. Excluding transfusion, the complication rate was 9.8%.
      Prolonged intubation greater than 48 hours occurred in 83 (1.5%) patients.
      Reintubation occurred in 72 (1.3%) patients. Readmission occurred in 398 (7.8%)
      patients. Reoperation was necessary in 273 (4.9%) patients with postoperative
      infection being the most common reason. The frailty-based score was shown to be
      predictive of any of the above events (P < 0.0001). The majority of patients
      (54.9%) in the group that had complications was found to have a frailty score of
      1 or higher. CONCLUSION: The predictors for any event included female sex,
      increased surgical time, combined anterior-posterior procedures, preoperative
      inpatient status, diabetes, smoking, American Society of Anesthesiologists class
      3 or higher, and increasing age. The frailty-based score is a viable option to
      predict morbidity in posterior cervical fusion. LEVEL OF EVIDENCE: 3.

PMID- 27689761
TI  - Is There an Association of Epidural Corticosteroid Injection With Postoperative
      Surgical Site Infection After Surgery for Lumbar Degenerative Spine Disease?
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To assess the relation between
      exposure to epidural steroid injection (ESI) before surgery and occurrence of
      surgical site infection (SSI) for degenerative lumbar spine conditions. SUMMARY
      OF BACKGROUND DATA: The effect of local ESI on the occurrence of SSI is
      controversial. METHODS: Patients who underwent surgery for degenerative lumbar
      spine conditions at two centers between 2005 and 2015 were identified. Primary
      outcome measure was SSI within 90 days requiring surgical intervention. RESULTS:
      A total of 5311 patients (age 57 +/- 16 years) were analyzed of which 945 (18%)
      had at least one ESI within 90 days of surgery. One hundred thirty-four (2.5%)
      patients developed an SSI requiring reoperation. No association of exposure or
      dose-response relationship was identified between ESI and SSI for any of the time
      periods (90-, 30-, and 30-90-day). Five (1.7%) of the 290 patients who had at
      least one ESI within 30 days before surgery had a postoperative infection
      compared to 129 (2.6%) of the 5021 in the non-ESI group (unadjusted odds ratio:
      0.67, 95% CI: 0.27-1.64, P = 0.376). Fifteen (2.0%) of the 761 patients who had
      at least one ESI within 30 to 90 days before surgery had a postoperative
      infection, compared to 119 (2.6%) of the 4550 in the non-ESI group (unadjusted
      odds ratio: 0.75, 95% CI: 0.44-1.29, P = 0.296). CONCLUSION: In this
      retrospective study we investigated whether an ESI and its timing influences the
      postoperative risk of an SSI. We found no association-exposure or dose-response
      relationship-between ESI and postoperative infection, even after adjusting for
      potential confounders, for any of the time periods (90-, 30-, and 30-90-day ESI).
      In addition, we did find that longer hospital stay, greater EBL, posterior
      approach, and drain placement were associated with higher infection rates. LEVEL
      OF EVIDENCE: 3.

PMID- 27689762
TI  - Remodeling of the Cervical Facet Joint After Minimally Invasive Microendoscopic
      Resection for Cervical Osteoid Osteoma.
AB  - STUDY DESIGN: Case report and systematic review of the literature. OBJECTIVE: To
      describe a rare case of remodeling of the cervical facet joint after the
      microendoscopic resection of an osteoid osteoma. SUMMARY OF BACKGROUND DATA:
      Osteoid osteoma, the third most common benign bone tumor, is often treated by
      image-guided percutaneous removal of the nidus. However, percutaneous resection
      poses technical difficulties when the tumor is located near the spinal cord or
      nerve roots. To our knowledge, there are no reports describing postoperative
      remodeling of the cervical facet joint after surgical resection of an osteoid
      osteoma. METHODS: A 13-year-old boy was presented with neck pain that became
      worse at night. Computed tomography showed an osteoid osteoma in the right 7th
      cervical superior articular process. We successfully resected the nidus of the
      osteoid osteoma using minimally invasive microendoscopy. RESULTS: The patient was
      symptom-free at the 1-year follow up, and computed tomography images showed new
      bone formation at the C6/7 facet joint. CONCLUSION: This case indicates that
      microendoscopic resection is safe and effective for treating a cervical osteoid
      osteoma. This technique allowed total resection of the nidus with only minimal
      damage to the adjacent soft tissue and bone, and induced remodeling of the
      resection site. LEVEL OF EVIDENCE: 4.

PMID- 27689763
TI  - The role of topical anesthetics in the management of chronic pruritus.

PMID- 27689764
TI  - Bioconjugation and Applications of Amino Functional Fluorescence Polymers.
AB  - Synthesis and novel applications of biofunctional polymers for diagnosis and
      therapy are promising area involving various research domains. Herein, three
      fluorescent polymers, poly(p-phenylene-co-thiophene), poly(p-phenylene), and
      polythiophene with amino groups (PPT-NH2 , PPP-NH2 , and PT-NH2 , respectively)
      are synthesized and investigated for cancer cell targeted imaging, drug delivery,
      and radiotherapy. Polymers are conjugated to anti-HER2 antibody for targeted
      imaging studies in nontoxic concentrations. Three cell lines (A549, Vero, and
      HeLa) with different expression levels of HER2 are used. In a model of HER2
      expressing cell line (A549), radiotherapy experiments are carried out and results
      show that all three polymers increase the efficacy of radiotherapy. This effect
      is even more increased when conjugated to anti-HER2. In the second part of this
      work, one of the selected polymers (PT-NH2 ) is conjugated with a drug model;
      methotrexate via pH responsive hydrazone linkage and a drug carrier property of
      PT-NH2 is demonstrated on neuroblastoma (SH-SY5Y) cell model. Our results
      indicate that, PPT-NH2 , PPP-NH2 , and PT-NH2 have a great potential as
      biomaterials for various bioapplications in cancer research.

PMID- 27689765
TI  - Increased lipogenesis in spite of upregulated hepatic 5'AMP-activated protein
      kinase in human non-alcoholic fatty liver.
AB  - AIMS: Molecular adaptations in human non-alcoholic fatty liver disease (NAFLD)
      are incompletely understood. This study investigated the main gene categories
      related to hepatic de novo lipogenesis and lipid oxidation capacity. METHODS:
      Liver specimens of 48 subjects were histologically classified according to
      steatosis severity. In-depth analyses were undertaken using real-time polymerase
      chain reaction, immunoblotting, and immunohistochemistry. Lipid profiles were
      analyzed by gas chromatography/flame ionization detection, and effects of key
      fatty acids were studied in primary human hepatocytes. RESULTS: Real-time
      polymerase chain reaction, immunoblotting, and immunohistochemistry indicated
      5'AMP-activated protein kinase (AMPK) to be increased with steatosis score >= 2
      (all P < 0.05), including various markers of de novo lipogenesis and lipid
      degradation (all P < 0.05). Regarding endoplasmic reticulum stress, X-Box binding
      protein-1 (XBP1) was upregulated in steatosis score >= 2 (P = 0.029) and
      correlated with plasma palmitate (r = 0.34; P = 0.035). Palmitate incubation of
      primary human hepatocytes increased XBP1 and downstream stearoyl CoA desaturase-1
      mRNA expression (both P < 0.05). Moreover, plasma and liver tissue exposed a
      NAFLD-related lipid profile with reduced polyunsaturated/saturated fatty acid
      ratio, increased palmitate and palmitoleate, and elevated lipogenesis and
      desaturation indices with steatosis score >= 2 (all P < 0.05). CONCLUSION: In
      humans with advanced fatty liver disease, hepatic AMPK protein is upregulated,
      potentially in a compensatory manner. Moreover, pathways of lipid synthesis and
      degradation are co-activated in subjects with advanced steatosis. Palmitate may
      drive lipogenesis by activating XBP1-mediated endoplasmic reticulum stress and
      represent a target for future dietary or pharmacological intervention.

PMID- 27689766
TI  - The ABCs of flower development: mutational analysis of AP1/FUL-like genes in rice
      provides evidence for a homeotic (A)-function in grasses.
AB  - The well-known ABC model describes the combinatorial interaction of homeotic
      genes in specifying floral organ identities. While the B- and C-functions are
      highly conserved throughout flowering plants and even in gymnosperms, the A
      function, which specifies the identity of perianth organs (sepals and petals in
      eudicots), remains controversial. One reason for this is that in most plants that
      have been investigated thus far, with Arabidopsis being a remarkable exception,
      one does not find recessive mutants in which the identity of both types of
      perianth organs is affected. Here we report a comprehensive mutational analysis
      of all four members of the AP1/FUL-like subfamily of MADS-box genes in rice
      (Oryza sativa). We demonstrate that OsMADS14 and OsMADS15, in addition to their
      function of specifying meristem identity, are also required to specify palea and
      lodicule identities. Because these two grass-specific organs are very likely
      homologous to sepals and petals of eudicots, respectively, we conclude that there
      is a floral homeotic (A)-function in rice as defined previously. Together with
      other recent findings, our data suggest that AP1/FUL-like genes were
      independently recruited to fulfil the (A)-function in grasses and some eudicots,
      even though other scenarios cannot be excluded and are discussed.

PMID- 27689767
TI  - Relationship Between Number of Household Members and Prevalence of Chronic
      Diseases: A Cross-Sectional Analysis of Korea Health Panel Data.

PMID- 27689768
TI  - A Conservative Technique for Repairing Class IV Composite Restorations.
AB  - Composite resin may make a restoration noticeable as time passes, on account of
      its color instability. The repair technique is a minimally invasive treatment for
      class IV composite resin restorations that show unsatisfactory coloration. Thus,
      the objective of the present article was to report a clinical case involving a
      conservative technique used for repairing a class IV composite resin restoration
      in the left maxillary central incisor and the replacement of a class IV
      restoration in the right maxillary central incisor.

PMID- 27689769
TI  - Microcomputed Tomography Evaluation of Polymerization Shrinkage of Class I
      Flowable Resin Composite Restorations.
AB  - The present study aimed to characterize the pattern and volume of polymerization
      shrinkage of flowable resin composites, including one conventional, two bulk
      fill, and one self-adhesive. Standardized class I preparations (2.5 mm depth * 4
      mm length * 4 mm wide) were performed in 24 caries-free human third molars that
      were randomly divided in four groups, according to the resin composite and
      adhesive system used: group 1 = Permaflo + Peak Universal Bond (PP); group 2 =
      Filtek Bulk Fill + Scotchbond Universal (FS); group 3 = Surefil SDR + XP Bond
      (SX); and group 4 = Vertise flow self-adhering (VE) (n=6). Each tooth was scanned
      three times using a microcomputed tomography (MUCT) apparatus. The first scan was
      done after the cavity preparation, the second after cavity filling with the
      flowable resin composite before curing, and the third after it was cured. The
      MUCT images were imported into three-dimensional rendering software, and
      volumetric polymerization shrinkage percentage was calculated for each sample.
      Data were submitted to one-way analysis of variance and post hoc comparisons. No
      significant difference was observed among PP, FS, and VE. SX bulk fill resin
      composite presented the lowest values of volumetric shrinkage. Shrinkage was
      mostly observed along the occlusal surface and part of the pulpal floor. In
      conclusion, polymerization shrinkage outcomes in a 2.5-mm deep class I cavity
      were material dependent, although most materials did not differ. The location of
      shrinkage was mainly at the occlusal surface.

PMID- 27689770
TI  - Microtensile Bond Strength of Composite Cement to Novel CAD/CAM Materials as a
      Function of Surface Treatment and Aging.
AB  - OBJECTIVES: To evaluate the effect of different surface treatments on the bond
      strength to a composite and a polymer-infiltrated ceramic CAD/CAM block after six
      month artificial aging. METHODS AND MATERIALS: Two types of CAD/CAM blocks
      (Cerasmart, GC; Enamic, Vita Zahnfabrik) were cut in slabs of 4-mm thickness,
      divided into six groups, and subjected to the following surface treatments: group
      1: no treatment; group 2: sandblasting (SB); group 3: SB + silane (Si); group 4:
      SB + Si + flowable composite (see below); group 5: 5% hydrofluoric acid etching
      (HF) + Si; and group 6: 37% phosphoric acid etching (H3PO4) + Si. Sections of the
      same group were luted together (n=3: 3 sandwich specimens/group) using a dual
      cure self-adhesive cement for all groups, except for the sections of group 4 that
      were luted using a light-curing flowable composite. After three weeks of storage
      in 0.5% chloramine at 37 degrees C, the sandwich specimens were sectioned in
      rectangular microspecimens and trimmed at the interface to a dumbbell shape (1.1
      mm diameter). One half of the specimens was subjected to a microtensile bond
      strength (MUTBS) test, and the other half was tested after six months of water
      storage (aging). Data were statistically analyzed with a linear mixed-effects
      model for the factors surface treatment, material type, and aging, together with
      their first-degree interactions (alpha=0.05). RESULTS: The lowest bond strengths
      were obtained in the absence of any surface treatment (group 1), while the
      highest MUTBSs were obtained when the surface was roughened by either SB or HF,
      this in combination with chemical adhesion through Si. Loss in bond strength was
      observed after six-month aging when either surface roughening or silanization, or
      both, were omitted. CONCLUSIONS: Both the composite and polymer-infiltrated
      ceramic CAD/CAM blocks appeared equally bonding-receptive regardless of the
      surface treatment used. Creating a microretentive surface by either SB or HF,
      followed by chemical adhesion using Si, is mandatory to maintain the bond
      strength after six months.

PMID- 27689771
TI  - Effect of Insufficient Light Exposure on Polymerization Kinetics of Conventional
      and Self-adhesive Dual-cure Resin Cements.
AB  - OBJECTIVES: The purpose of this study was to investigate the influence of
      insufficient light exposure on the polymerization of conventional and self
      adhesive dual-cure resin cements under ceramic restorations. METHODS: Two
      conventional dual-cure resin cements (Rely-X ARC, Duolink) and two self-adhesive
      resin cements (Rely-X U200, Maxcem Elite) were polymerized under different curing
      modes (dual-cure or self-cure), curing times (20 and 120 seconds), and thickness
      of a ceramic overlay (2 and 4 mm). Polymerization kinetics was measured by
      Fourier transform infrared spectroscopy for the initial 10 minutes and after 24
      hours. Data were analyzed using mixed model analysis of variance (ANOVA), one-way
      ANOVA/Student-Newman-Keuls post hoc test, and paired t-test (alpha=0.05).
      RESULTS: When light-curing time was set to 20 seconds, the presence of the
      ceramic block significantly affected the degree of conversion (DC) of all resin
      cements. Especially, the DC of the groups with 20 seconds of light-curing time
      under 4 mm of ceramic thickness was even lower than that of the self-cured groups
      at 24 hours after polymerization (p<0.05). However, when light-curing time was
      set to 120 seconds, a similar DC compared with the group with direct light
      exposure (p>0.05) was achieved in all dual-cure groups except Maxcem Elite, at 24
      hours after polymerization. CONCLUSIONS: For both conventional and self-adhesive
      dual-cure resin cements, insufficient light exposure (20 seconds of light-curing
      time) through thick ceramic restoration (4 mm thick) resulted in a DC even lower
      than that of self-curing alone.

PMID- 27689772
TI  - Effect of Nd:YAG Laser Irradiation Pretreatment on the Long-Term Bond Strength of
      Etch-and-Rinse Adhesive to Dentin.
AB  - PURPOSE: To investigate the effect of neodymium-doped yttrium aluminum garnet
      (Nd:YAG) laser irradiation pretreatment on the long-term bond strength of an etch
      and-rinse adhesive to dentin. METHODS: Fifty molars were sectioned parallel to
      the occlusal plane and randomly divided into two groups (n=25 per group): control
      group (no treatment) and laser group (dentin surfaces were treated with Nd:YAG
      laser at a setting of 100 mJ/10 Hz). Afterward, resin was bonded to the dentin
      surface using a two-step etch-and-rinse adhesive (Adper SingleBond 2), and then
      150 beams of each group were produced. Each group was divided into three
      subgroups (n=50 each group): 24 hours of water storage, thermocycling, and NaOCl
      storage. The microtensile bond strength (MTBS), failure modes, nanoleakage
      expression, and Masson's trichrome staining were evaluated. An additional 20
      molars were sectioned to obtain 2-mm-thick flat dentin slices. These slices were
      randomly divided into control and laser-treated groups as mentioned previously.
      Then slices of each group were examined by scanning electron microscopy,
      attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X
      ray diffraction (XRD), and the Knoop hardness test. RESULTS: The results of ATR
      FTIR and Masson's trichrome verified that laser irradiation partly removed
      collagen fibers from the dentin surface; however, no significant difference was
      found in the Knoop hardness (p>0.05). The XRD result showed similar crystalline
      structure regardless of laser pretreatment. There is no significant difference in
      short-term MTBS between control and laser-treated groups (p>0.05); however, long
      term MTBS differed between the groups (p>0.05). Furthermore, the laser-treated
      group showed less silver deposition than the control group after aging (p<0.05).
      CONCLUSION: Pretreatment by Nd:YAG laser irradiation appeared to have a positive
      effect on the adhesive-dentin bonding in vitro test, and the bonding
      effectiveness could be preserved after aging.

PMID- 27689773
TI  - Evaluation of root maturation after revitalization in immature permanent teeth
      with nonvital pulps by cone beam computed tomography and conventional
      radiographs.
AB  - AIM: To investigate the response of immature permanent teeth with nonvital pulps
      after revitalization procedures using cone beam computed tomography imaging and
      conventional radiograph. METHODOLOGY: Clinical records of patients who had
      undergone revitalization between 1997 and 2014 were collected. Seventeen patients
      attended the follow-up examination. Clinical examination and radiographic
      examination by means of CBCT imaging and conventional radiographs were conducted
      to evaluate treatment outcomes, especially the dimensional changes of the root
      and the pattern of root maturation. Statistical analysis was conducted using
      Fisher's exact test and Monte Carlo test to investigate the effect of potential
      outcome predictors. RESULTS: For the follow-up period as far as 96 months,
      thirteen teeth (76%) were classified as a 'success'. Conventional radiographs
      showed various degrees of dimensional changes in the immature roots ranging from
      0% to 73% changes. The mean percentage changes of root length and root wall
      thickness were 14.38 +/- 20.92% and 13.82 +/- 11.17%, respectively. CBCT images
      illustrated various patterns of root maturation including incomplete root
      development with wide-open apices and fully formed roots with various apical
      shapes. Root canal contents varied radiographically from empty canals to many
      degrees of unpredictable patterning of radiopaque deposits. CONCLUSION:
      Revitalization in immature teeth with nonvital pulps resulted in unpredictable
      responses in terms of continued root development. Various types of root
      maturation and root canal contents were observed radiographically, which were
      different from typical root development.

PMID- 27689774
TI  - Impact of Nonthermal Atmospheric Plasma on the Structure of Cellulose: Access to
      Soluble Branched Glucans.
AB  - We have investigated the effect of non-thermal atmospheric plasma (NTAP) on the
      structure of microcrystalline cellulose. In particular, by means of different
      characterization methods, we demonstrate that NTAP promotes the partial cleavage
      of the beta-1,4 glycosidic bond of cellulose leading to the release of short
      chain cellodextrins that are reassembled in situ, preferentially at the C6
      position, to form branched glucans with either a glucosyl or anhydroglucosyl
      terminal residue. The ramification of cellulosic chain induced by NTAP yields
      branched glucans that are soluble in DMSO or in water, thus opening a
      straightforward access to processable glucans from cellulose. Importantly, the
      absence of solvent and catalyst considerably facilitates downstream processing as
      compared to (bio)catalytic processes which typically occur in diluted conditions.

PMID- 27689775
TI  - Probing Membrane Viscosity and Interleaflet Friction of Supported Lipid Bilayers
      by Tracking Electrostatically Adsorbed, Nano-Sized Vesicles.
AB  - Particle tracking is used to measure the diffusional motion of nanosized (~100
      nm), lipid vesicles that are electrostatically adsorbed onto a solid supported
      lipid bilayer. It is found that the motion of membrane-adhering vesicles is
      Brownian and depends inversely on the vesicle size, but is insensitive to the
      vesicle surface charge. The measured diffusivity agrees well with the Evans
      Sackmann model for the diffusion of inclusions in supported, fluidic membranes.
      The agreement implies that the vesicle motion is coupled to that of a nanoscopic
      lipid cluster in the upper leaflet, which slides over the lower leaflet. The
      diffusivity of membrane-adhering vesicles is therefore predominantly governed by
      the interleaflet friction coefficient, while the diffusivity of single lipids is
      mainly governed by the membrane viscosity. Combined with fluorescence recovery
      after photobleaching analysis, the interleaflet friction coefficient and the
      membrane viscosity are determined by applying the Evans-Sackmann model to the
      measured diffusivity of membrane adhering vesicles and that of supported membrane
      lipids. This approach provides an alternative to existing methods for measuring
      the interleaflet friction coefficient and the membrane viscosity.

PMID- 27689776
TI  - Groundwater Exploration in India Using Hydrogeological & Resistivity Method in
      Past 60 Years.

PMID- 27689778
TI  - Highly Enantioselective Synthesis of Indolines: Asymmetric Hydrogenation at
      Ambient Temperature and Pressure with Cationic Ruthenium Diamine Catalysts.
AB  - A highly enantioselective synthesis of indolines by asymmetric hydrogenation of
      1H-indoles and 3H-indoles at ambient temperature and pressure, catalyzed by
      chiral phosphine-free cationic ruthenium complexes, has been developed. Excellent
      enantio- and diastereoselectivities (up to >99 % ee, >20:1 d.r.) were obtained
      for a wide range of indole derivatives, including unprotected 2-substituted and
      2,3-disubstituted 1H-indoles, as well as 2-alkyl- and 2-aryl-substituted 3H
      indoles.

PMID- 27689777
TI  - Gas chromatography/mass spectrometry measurement of xenon in gas-loaded liposomes
      for neuroprotective applications.
AB  - RATIONALE: We have produced a liposomal formulation of xenon (Xe-ELIP) as a
      neuroprotectant for inhibition of brain damage in stroke patients. This mandates
      development of a reliable assay to measure the amount of dissolved xenon released
      from Xe-ELIP in water and blood samples. METHODS: Gas chromatography/mass
      spectrometry (GC/MS) was used to quantify xenon gas released into the headspace
      of vials containing Xe-ELIP samples in water or blood. In order to determine
      blood concentration of xenon in vivo after Xe-ELIP administration, 6 mg of Xe
      ELIP lipid was infused intravenously into rats. Blood samples were drawn directly
      from a catheterized right carotid artery. After introduction of the samples, each
      vial was allowed to equilibrate to 37 degrees C in a water bath, followed by 20
      minutes of sonication prior to headspace sampling. Xenon concentrations were
      calculated from a gas dose-response curve and normalized using the published
      xenon water-gas solubility coefficient. RESULTS: The mean corrected percent of
      xenon from Xe-ELIP released into water was 3.87 +/- 0.56% (SD, n = 8),
      corresponding to 19.3 +/- 2.8 MUL/mg lipid, which is consistent with previous
      independent Xe-ELIP measurements. The corresponding xenon content of Xe-ELIP in
      rat blood was 23.38 +/- 7.36 MUL/mg lipid (n = 8). Mean rat blood xenon
      concentration after intravenous administration of Xe-ELIP was 14 +/- 10 MUM,
      which is approximately 15% of the estimated neuroprotective level. CONCLUSIONS:
      Using this approach, we have established a reproducible method for measuring
      dissolved xenon in fluids. These measurements have established that
      neuroprotective effects can be elicited by less than 20% of the calculated
      neuroprotective xenon blood concentration. More work will have to be done to
      establish the protective xenon pharmacokinetic range. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27689779
TI  - Sub-5 nm Patterning by Directed Self-Assembly of Oligo(Dimethylsiloxane) Liquid
      Crystal Thin Films.
AB  - Highly ordered nanopatterns are obtained at sub-5 nm periodicities by the
      graphoepitaxial directed self-assembly of monodisperse, oligo(dimethylsiloxane)
      liquid crystals. These hybrid organic/inorganic liquid crystals are of high
      interest for nanopatterning applications due to the combination of their
      ultrasmall feature sizes and their ability to be directed into highly ordered
      domains without additional annealing.

PMID- 27689780
TI  - A policy of routine umbilical cord blood gas analysis decreased missing samples
      from high-risk births.
AB  - AIM: This study compared obstetric units practicing routine or selective
      umbilical cord blood gas analysis, with respect to the risk of missing samples in
      high-risk deliveries and in infants with birth asphyxia. METHODS: This was a
      Swedish population-based cohort study that used register data for 155 235
      deliveries of live singleton infants between 2008 and 2014. Risk ratios and 95%
      confidence intervals were calculated to estimate the association between routine
      and selective umbilical cord blood gas sampling strategies and the risk of
      missing samples. RESULTS: Selective sampling increased the risk ratios when
      routine sampling was used as the reference, with a value of 1.0, and these were
      significant in high-risk deliveries and birth asphyxia. The risk ratios for
      selective sampling were large-for-gestational age (9.07), preterm delivery at up
      to 36 weeks of gestation (8.24), small-for-gestational age (7.94), two or more
      foetal scalp blood samples (5.96), an Apgar score of less than seven at one
      minute (2.36), emergency Caesarean section (1.67) and instrumental vaginal
      delivery (1.24). CONCLUSION: Compared with routine sampling, selective umbilical
      cord blood gas sampling significantly increased the risks of missing samples in
      high-risk deliveries and in infants with birth asphyxia.

PMID- 27689782
TI  - Computational chemistry and computer-aided drug discovery: Part II.

PMID- 27689781
TI  - Poly(3-hydroxyoctanoate), a promising new material for cardiac tissue
      engineering.
AB  - Cardiac tissue engineering (CTE) is currently a prime focus of research because
      of an enormous clinical need. In the present work, a novel functional material,
      poly(3-hydroxyoctanoate), P(3HO), a medium chain-length polyhydroxyalkanoate
      (PHA), produced using bacterial fermentation, was studied as a new potential
      material for CTE. Engineered constructs with improved mechanical properties,
      crucial for supporting the organ during new tissue regeneration, and enhanced
      surface topography, to allow efficient cell adhesion and proliferation, were
      fabricated. Results showed that the mechanical properties of the final patches
      were close to that of cardiac muscle. Biocompatibility of neat P(3HO) patches,
      assessed using neonatal ventricular rat myocytes (NVRM), showed that the polymer
      was as good as collagen in terms of cell viability, proliferation and adhesion.
      Enhanced cell adhesion and proliferation properties were observed when porous and
      fibrous structures were incorporated into the patches. In addition, no
      deleterious effect was observed on adult cardiomyocyte contraction when
      cardiomyocytes were seeded on the P(3HO) patches. Hence, P(3HO)-based
      multifunctional cardiac patches are promising constructs for efficient CTE. This
      work will have a positive impact on the development of P(3HO) and other PHAs as a
      novel new family of biodegradable functional materials with huge potential in a
      range of different biomedical applications, particularly CTE, leading to further
      interest and exploitation of these materials. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27689783
TI  - Resilience Analytics with Application to Power Grid of a Developing Region.
AB  - Infrastructure development of volatile regions is a significant investment by
      international government and nongovernment organizations, with attendant
      requirements for risk management. Global development banks may be tasked to
      manage these investments and provide a channel between donors and borrowers.
      Moreover, various stakeholders from the private sector, local and international
      agencies, and the military can be engaged in conception, planning, and
      implementation of constituent projects. Emergent and future conditions of
      military conflict, politics, economics, technology, environment, behaviors,
      institutions, and society that stress infrastructure development are prevalent,
      and funding mechanisms are vulnerable to fraud, waste, and abuse. This article
      will apply resilience analytics with scenario-based preferences to identify the
      stressors that most influence a prioritization of initiatives in the electric
      power sector of Afghanistan. The resilience in this article is conceived in terms
      of the degree of disruption of priorities when stressors influence the
      preferences of stakeholders, and ultimately a prioritization of initiatives. The
      ancillary results include an understanding of which initiatives contribute most
      and least across strategic criteria and which criteria have the most impact for
      the analysis. The article concludes with recommendations for risk monitoring and
      risk management of the portfolio of stressors through the life cycle and horizon
      of grid capacity expansion.

PMID- 27689784
TI  - The Proteolytic Activity of Porphyromonas gingivalis Is Critical in a Murine
      Model of Periodontitis.
AB  - BACKGROUND: Porphyromonas gingivalis (Pg), a periodontal pathogen, has
      interstrain variability in virulence. The aim of this study is to determine the
      contribution of the cell invasion ability and proteolytic activity of Pg to its
      virulence in a murine model of periodontitis. METHODS: Three clinical isolates:
      KUMC-P1 (P1: low cell invasion ability and low proteolytic activity); KUMC-P4
      (P4: low cell invasion ability and high proteolytic activity); and KUMC-P8 (P8:
      high cell invasion ability and low proteolytic activity), were orally
      administered into mice. Alveolar bone loss (ABL) and bacterial invasion of
      gingival tissues were measured. Additionally, effects of the three strains on
      transepithelial electrical resistance (TER) and the levels of tight-junction
      proteins in gingival epithelial cells were evaluated in vitro. RESULTS: ABL
      induced by the three strains was in the sequence P4 > P8 > P1, and the difference
      between P8 and P1 was not significant. Amounts of Pg detected within the gingival
      tissues were increased by all three strains compared with the sham group, and
      bacterial level was positively correlated with ABL. In vitro, P4 had a greater
      effect than the other strains on epithelial barrier disruption, as evidenced by
      the reduced levels of tight-junction proteins and TER. CONCLUSION: The
      proteolytic activity of Pg was more critical than the cell invasion ability for
      inducing experimental periodontitis in mice, which could be attributed to the
      paracellular pathway dependence of gingival tissue invasion by bacteria in the
      mice.

PMID- 27689785
TI  - Methionine sulfoximine supplementation enhances productivity in GS-CHOK1SV cell
      lines through glutathione biosynthesis.
AB  - In Lonza Biologics' GS Gene Expression SystemTM, recombinant protein-producing GS
      CHOK1SV cell lines are generated by transfection with an expression vector
      encoding both GS and the protein product genes followed by selection in MSX and
      glutamine-free medium. MSX is required to inhibit endogenous CHOK1SV GS, and in
      effect create a glutamine auxotrophy in the host that can be complemented by the
      expression vector encoded GS in selected cell lines. However, MSX is not a
      specific inhibitor of GS as it also inhibits the activity of GCL (a key enzyme in
      the glutathione biosynthesis pathway) to a similar extent. Glutathione species
      (GSH and GSSG) have been shown to provide both oxidizing and reducing equivalents
      to ER-resident oxidoreductases, raising the possibility that selection for
      transfectants with increased GCL expression could result in the isolation of GS
      CHOKISV cell lines with improved capacity for recombinant protein production. In
      this study we have begun to address the relationship between MSX supplementation,
      the amount of intracellular GCL subunit and mAb production from a panel of GS
      CHOK1SV cell lines. We then evaluated the influence of reduced GCL activity on
      batch culture of an industrially relevant mAb-producing GS-CHOK1SV cell line. To
      the best of our knowledge, this paper describes for the first time the change in
      expression of GCL subunits and recombinant mAb production in these cell lines
      with the degree of MSX supplementation in routine subculture. Our data also shows
      that partial inhibition of GCL activity in medium containing 75 uM MSX increases
      mAb productivity, and its more specific inhibitor BSO used at a concentration of
      80 uM in medium increases the specific rate of mAb production eight-fold and the
      concentration in harvest medium by two-fold. These findings support a link
      between the inhibition of glutathione biosynthesis and recombinant protein
      production in industrially relevant systems and provide a process-driven method
      for increasing mAb productivity from GS-CHOK1SV cell lines. (c) 2016 American
      Institute of Chemical Engineers Biotechnol. Prog., 33:17-25, 2017.

PMID- 27689786
TI  - Health promotion and information provision during long-term follow-up for
      childhood cancer survivors: A service evaluation.
AB  - Health promotion is an important component of long-term follow-up (LTFU) care for
      childhood cancer survivors (CCS). However, little information exists about how
      survivors perceive their own health promotion needs. As part of a service
      evaluation, 51 CCS who had previously attended the LTFU clinic took part in a
      single semistructured interview to seek their views on information they had
      received regarding late adverse effects (LAEs) of treatment, the purpose of LTFU,
      and the provision of health promotion information. Although most (93%) CCS were
      satisfied with the information received about LAEs, 37% desired further details.
      Over half (59%) believed that the purpose of LTFU was to screen for LAEs, whereas
      31% felt that it was to check for relapse. No survivor reported health promotion
      to be an aim of LTFU; only 14% of CCS expected to receive healthy lifestyle
      advice, and fewer than 10% wanted dietary and physical activity advice. Most
      (88%) CCS felt that their hospital-based health care professional was best placed
      to give healthy lifestyle advice, but there was no consensus about the optimum
      timing for health promotion. CCS varied in their knowledge, needs, and wishes
      regarding LTFU care. The results of this evaluation strongly indicate that the
      profile of health promotion needs to be raised within our service and identifies
      issues that may be pertinent to similar services. Further research is needed to
      understand the views of CCS regarding health promotion and lifestyle behaviors,
      with the aim of tailoring and improving the delivery of effective health
      education to CCS.

PMID- 27689787
TI  - Marijuana use among young people in an era of policy change: what does recent
      evidence tell us?

PMID- 27689788
TI  - Experiences of therapeutic relationships on hospital wards, dissociation, and
      making connections.
AB  - An interpretive phenomenological analysis sought to explore how people reporting
      moderate to high levels of dissociation experienced relationships with
      multidisciplinary hospital ward staff. Three superordinate themes were developed.
      First, the theme "multiple me and multiple them" explores the instability
      experienced by the participants as they managed their dissociative experiences
      alongside many inconsistencies. Second, "recognizing, meeting, or neglecting
      interpersonal and care needs" reflects on participants' needs within therapeutic
      relationships. Third, "between the needs of the internal system: navigating
      between 'better on my own' and 'someone to talk to'" discusses the confusion and
      understanding around dissociation and the importance of working with parts, not
      around them. Findings suggested that the current culture of some hospital wards
      directly influenced participants' distress, which could lead to further
      dissociation as a means of coping with perceived threats. Reflections on
      relational complexities and developing ward-based treatment are discussed.

PMID- 27689789
TI  - Feasibility of rehabilitation using the single-joint hybrid assistive limb to
      facilitate early recovery following total knee arthroplasty: A pilot study.
AB  - We aimed to evaluate the feasibility of robot-assisted rehabilitation in an early
      postoperative setting to improve knee mobility following total knee arthroplasty
      (TKA). A total of 20 patients were alternatively assigned to robotassisted
      rehabilitation (n = 10; all women) or a control group (n = 10; 2 men and 8
      women). The use of a single-joint hybrid assistive limb (HAL-SJ) in active
      assistive knee exercise was performed for the robot-assisted rehabilitation group
      while the control patients underwent conventional active assistive knee exercise.
      We measured the extension lag (defined as the difference between active and
      passive range of knee extension). We also evaluated the visual analog scale score
      (VAS) during active movements and active assistive movement. Concerning the
      extension lag, the robot-assisted rehabilitation group showed 89.4% +/- 15.7%
      improvement (p < 0.01) while the control group showed 34.8% +/- 32.1% improvement
      (p = 0.016). As to the VAS, the robot-assisted rehabilitation group showed 40.7%
      +/- 23.5% improvement while the control group showed 20.4% +/- 25.8% improvement
      (p < 0.01). The use of HAL-SJ may facilitate early recovery from knee surgery and
      prevent long-term complications such as quadriceps arthrogenic muscle inhibition.

PMID- 27689791
TI  - Teaching Evidence-Based Practice across Curricula-An Overview of a Professional
      Development Course for Occupational Therapy Educators.
AB  - A professional development course for occupational therapy educators about
      teaching evidence-based practice (EBP) was developed and piloted. The course was
      developed to promote increased awareness of resources and methods for teaching
      EBP that are applicable across entry-level curricula. Participants included full
      time faculty (n = 7) from one entry-level occupational therapy program in the New
      York City area. The results of the pilot informed refinement of the course in
      preparation for delivery to a wider audience of educators. This paper provides a
      description of the course, results of the pilot, and implications for future
      delivery of the course.

PMID- 27689792
TI  - Development of ligustrazine hydrochloride carboxymethyl chitosan and collagen
      microspheres: Formulation optimization, characterization, and vitro release.
AB  - This study investigates the preparation of ligustrazine hydrochloride
      carboxymethyl chitosan and collagen microspheres. This experiment investigates
      effects of the ratio of carboxymethyl chitosan and collagen blend, water to oil
      ratio, stirring speed, and other factors on the microsphere properties. The
      experiment had the following conditions: a 1:2 proportion of carboxymethyl
      chitosan and collagen, a 1:2 proportion of drugs and materials, a 5:1 proportion
      of oil phase and water phase, 0.5% of span80, a 600r/min stirring speed, 3 ml of
      a cross-linking agent, 3 h of cross-linking curing, 1.25 +/- 0.05 mm diameter LTH
      microcapsules, a 54.08% envelop rate, and a 14.16% carrier rate. The microspheres
      release rate reached 66% within 1 h, then steadily released within 5 h in vitro.
      The experimental results showed that the ligustrazine hydrochloride microsphere
      production process was stable and exhibited a good release effect compared with
      other ligustrazine hydrochloride tablets and pills.

PMID- 27689793
TI  - AHRQ Director Sets Course for Agency's Health Services Research.

PMID- 27689794
TI  - Hidden in Plain Sight: The Overlooked Role of Pulmonary Macrophages in the
      Pathogenesis of Asthma.

PMID- 27689796
TI  - October Highlights/Papers by Junior Investigators/NIH News.

PMID- 27689795
TI  - Persistent Pathology in Influenza-Infected Mouse Lungs.

PMID- 27689797
TI  - A New Beginning for the Red Journal.

PMID- 27689798
TI  - 1800MHz Microwave Induces p53 and p53-Mediated Caspase-3 Activation Leading to
      Cell Apoptosis In Vitro.
AB  - Recent studies have reported that exposure of mammalian cells to microwave
      radiation may have adverse effects such as induction of cell apoptosis. However,
      the molecular mechanisms underlying microwave induced mammalian cell apoptosis
      are not fully understood. Here, we report a novel mechanism: exposure to 1800MHz
      microwave radiation induces p53-dependent cell apoptosis through cytochrome c
      mediated caspase-3 activation pathway. We first measured intensity of microwave
      radiation from several electronic devices with an irradiation detector. Mouse
      NIH/3T3 and human U-87 MG cells were then used as receivers of 1800MHz
      electromagnetic radiation (EMR) at a power density of 1209 mW/m2. Following EMR
      exposure, cells were analyzed for viability, intracellular reactive oxygen
      species (ROS) generation, DNA damage, p53 expression, and caspase-3 activity. Our
      analysis revealed that EMR exposure significantly decreased viability of NIH/3T3
      and U-87 MG cells, and increased caspase-3 activity. ROS burst was observed at 6
      h and 48 h in NIH/3T3 cells, while at 3 h in U-87 MG cells. Hoechst 33258
      staining and in situ TUNEL assay detected that EMR exposure increased DNA damage,
      which was significantly restrained in the presence of N-acetyl-L-cysteine (NAC,
      an antioxidant). Moreover, EMR exposure increased the levels of p53 protein and
      p53 target gene expression, promoted cytochrome c release from mitochondrion, and
      increased caspase-3 activity. These events were inhibited by pretreatment with
      NAC, pifithrin-alpha (a p53 inhibitor) and caspase inhibitor. Collectively, our
      findings demonstrate, for the first time, that 1800MHz EMR induces apoptosis
      related events such as ROS burst and more oxidative DNA damage, which in turn
      promote p53-dependent caspase-3 activation through release of cytochrome c from
      mitochondrion. These findings thus provide new insights into physiological
      mechanisms underlying microwave-induced cell apoptosis.

PMID- 27689799
TI  - ATX-2, the C. elegans Ortholog of Human Ataxin-2, Regulates Centrosome Size and
      Microtubule Dynamics.
AB  - Centrosomes are critical sites for orchestrating microtubule dynamics, and
      exhibit dynamic changes in size during the cell cycle. As cells progress to
      mitosis, centrosomes recruit more microtubules (MT) to form mitotic bipolar
      spindles that ensure proper chromosome segregation. We report a new role for ATX
      2, a C. elegans ortholog of Human Ataxin-2, in regulating centrosome size and MT
      dynamics. ATX-2, an RNA-binding protein, forms a complex with SZY-20 in an RNA
      independent fashion. Depleting ATX-2 results in embryonic lethality and
      cytokinesis failure, and restores centrosome duplication to zyg-1 mutants. In
      this pathway, SZY-20 promotes ATX-2 abundance, which inversely correlates with
      centrosome size. Centrosomes depleted of ATX-2 exhibit elevated levels of
      centrosome factors (ZYG-1, SPD-5, gamma-Tubulin), increasing MT nucleating
      activity but impeding MT growth. We show that ATX-2 influences MT behavior
      through gamma-Tubulin at the centrosome. Our data suggest that RNA-binding
      proteins play an active role in controlling MT dynamics and provide insight into
      the control of proper centrosome size and MT dynamics.

PMID- 27689800
TI  - Estimating Age-Specific Immunity and Force of Infection of Varicella Zoster Virus
      in Norway Using Mixture Models.
AB  - This study applies mixture modelling to examine age-specific immunity to
      varicella zoster virus (VZV) infection in Norway based on the first large-scale
      serological study in the general population. We estimated the seropositive
      proportions at different ages and calculated the underlying force of infection by
      using a sample of 2103 residual sera obtained from patients seeking primary and
      hospital care. A rapid increase in the VZV-associated immunity is observed in the
      first years of life with 63% of children being immune by age 5. The increase in
      the immunity levels slows down thereafter, with a large proportion of adults
      still susceptible by age 20 (around 14.5%), thus at risk of serious sequelae of
      varicella infection. The corresponding force of infection peaks during the
      preschool period, subsequently declines to a minimum between ages 10 and 20
      years, and afterwards moderately increases to reach a plateau lasting throughout
      the childbearing period. In comparison with the traditional cut-off approach,
      mixture modelling used the whole data without producing any inconclusive cases,
      led to an unbiased classification of individuals between susceptible and immune,
      and provided a smoother immune profile by age. These findings represent an
      important step towards any decision about the introduction of varicella
      vaccination in Norway, as they are a primary input for mathematical transmission
      models aimed at evaluating potential vaccination scenarios.

PMID- 27689801
TI  - Antecolic versus retrocolic reconstruction after partial pancreaticoduodenectomy.
AB  - BACKGROUND: Pancreatic cancer remains one of the five leading causes of cancer
      deaths in industrialized nations. For adenocarcinomas in the head of the gland
      and premalignant lesions, partial pancreaticoduodenectomy represents the standard
      treatment for resectable tumours. The gastro- or duodenojejunostomy after partial
      pancreaticoduodenectomy can be reestablished via either an antecolic or a
      retrocolic route. The debate about the more favourable technique for bowel
      reconstruction is ongoing. OBJECTIVES: To compare the effectiveness and safety of
      antecolic and retrocolic gastro- or duodenojejunostomy after partial
      pancreaticoduodenectomy. SEARCH METHODS: We conducted a systematic literature
      search on 29 September 2015 to identify all randomised controlled trials in the
      Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library
      2015, issue 9, MEDLINE (1946 to September 2015), and EMBASE (1974 to September
      2015). We applied no language restrictions. We handsearched reference lists of
      identified trials to identify further relevant trials, and searched the trial
      registry clinicaltrials.gov for ongoing trials. SELECTION CRITERIA: We considered
      all randomised controlled trials that compared antecolic versus retrocolic
      reconstruction of bowel continuity after partial pancreaticoduodenectomy for any
      given indication to be eligible. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened the identified references and extracted data from the
      included trials. The same two review authors independently assessed risk of bias
      of included trials, according to standard Cochrane methodology. We used a random
      effects model to pool the results of the individual trials in a meta-analysis. We
      used odds ratios to compare binary outcomes and mean differences for continuous
      outcomes. MAIN RESULTS: Of a total of 216 citations identified by the systematic
      literature search, we included six randomised controlled trials (reported in nine
      publications), with a total of 576 participants. We identified a moderate
      heterogeneity of methodological quality and risk of bias of the included trials.
      None of the pooled results for our main outcomes of interest showed significant
      differences: delayed gastric emptying (OR 0.60; 95% CI 0.31 to 1.18; P = 0.14),
      mortality (RD -0.01; 95% CI -0.03 to 0.02; P = 0.72), postoperative pancreatic
      fistula (OR 0.98; 95% CI 0.65 to 1.47; P = 0.92), postoperative haemorrhage (OR
      0.79; 95% CI 0.38 to 1.65; P = 0.53), intra-abdominal abscess (OR 0.93; 95% CI
      0.52 to 1.67; P = 0.82), bile leakage (OR 0.89; 95% CI 0.36 to 2.15; P = 0.79),
      reoperation rate (OR 0.59; 95% CI 0.27 to 1.31; P = 0.20), and length of hospital
      stay (MD -0.67; 95%CI -2.85 to 1.51; P = 0.55). Furthermore, the perioperative
      outcomes duration of operation, intraoperative blood loss and time to NGT removal
      showed no relevant differences. Only one trial reported quality of life, on a
      subgroup of participants, also without a significant difference between the two
      groups at any time point. The overall quality of the evidence was only low to
      moderate, due to heterogeneity, some inconsistency and risk of bias in the
      included trials. AUTHORS' CONCLUSIONS: There was low to moderate quality evidence
      suggesting no significant differences in morbidity, mortality, length of hospital
      stay, or quality of life between antecolic and retrocolic reconstruction routes
      for gastro- or duodenojejunostomy. Due to heterogeneity in definitions of the
      endpoints between trials, and differences in postoperative management, future
      research should be based on clearly defined endpoints and standardised
      perioperative management, to potentially elucidate differences between these two
      procedures. Novel strategies should be evaluated for prophylaxis and treatment of
      common complications, such as delayed gastric emptying.

PMID- 27689802
TI  - Microbiome in the Apical Root Canal System of Teeth with Post-Treatment Apical
      Periodontitis.
AB  - INTRODUCTION: Bacteria present in the apical root canal system are directly
      involved with the pathogenesis of post-treatment apical periodontitis. This study
      used a next-generation sequencing approach to identify the bacterial taxa
      occurring in cryopulverized apical root samples from root canal-treated teeth
      with post-treatment disease. METHODS: Apical root specimens obtained during
      periradicular surgery of ten adequately treated teeth with persistent apical
      periodontitis were cryogenically ground. DNA was extracted from the powder and
      the microbiome was characterized on the basis of the V4 hypervariable region of
      the 16S rRNA gene by using paired-end sequencing on Illumina MiSeq device.
      RESULTS: All samples were positive for the presence of bacterial DNA. Bacterial
      taxa were mapped to 11 phyla and 103 genera composed by 538 distinct operational
      taxonomic units (OTUs) at 3% of dissimilarity. Over 85% of the sequences belonged
      to 4 phyla: Proteobacteria, Firmicutes, Fusobacteria and Actinobacteria. In
      general, these 4 phyla accounted for approximately 80% of the distinct OTUs found
      in the apical root samples. Proteobacteria was the most abundant phylum in 6/10
      samples. Fourteen genera had representatives identified in all cases. Overall,
      the genera Fusobacterium and Pseudomonas were the most dominant. Enterococcus was
      found in 4 cases, always in relatively low abundance. CONCLUSIONS: This study
      showed a highly complex bacterial community in the apical root canal system of
      adequately treated teeth with persistent apical periodontitis. This suggests that
      this disease is characterized by multispecies bacterial communities and has a
      heterogeneous etiology, because the community composition largely varied from
      case to case.

PMID- 27689803
TI  - Correction: Direct Correlation between Motile Behavior and Protein Abundance in
      Single Cells.
AB  - [This corrects the article DOI: 10.1371/journal.pcbi.1005041.].

PMID- 27689806
TI  - Antimicrobial Silver Nanoclusters Bearing Biocompatible Phosphorylcholine-Based
      Zwitterionic Protection.
AB  - Infection is one of the most serious issues in medical treatments leading to the
      development of several antimicrobial agents. In particular, silver ions released
      from silver substrates is well-known as a reliable antimicrobial agent that
      either kills the microorganisms or inhibits their growth. Unfortunately, many
      reports have shown that silver-based antimicrobial agents are toxic for human
      cells as well. To improve the biocompatibility of silver antimicrobial agents, we
      have synthesized thiol-terminated phosphorylcholine (PC-SH)-protected silver
      nanoclusters (PC-AgNCs) via strong thiol-metal coordination with controlled
      ultrasmall size of the clusters. A change in plasmon-like optical absorption was
      studied to affirm the successful synthesis of small thiolated AgNCs through the
      absorption spectra that become molecular-like for the AgNCs. We observed that PC
      AgNCs were spherical with an average diameter of <2 nm. The ultrasmall size
      clusters were exceedingly immobilized by the PC-SH on the surface, resulting in
      excellent biocompatibility and antibacterial activity simultaneously. The
      biocompatible, antimicrobial PC-AgNCs exhibit interesting advantages compared
      with other silver antimicrobial agents for medical applications.

PMID- 27689805
TI  - The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity
      and Affect Coagulation In Vitro.
AB  - Organophosphates (OPs) are potentially able to affect serine proteases by
      reacting with their active site. The potential effects of OPs on coagulation
      factors such as thrombin and on coagulation tests have been only partially
      characterized and potential interactions with OPs antidotes such as oximes and
      muscarinic blockers have not been addressed. In the current study, we
      investigated the in vitro interactions between coagulation, thrombin, the OP
      paraoxon, and its antidotes obidoxime and atropine. The effects of these
      substances on thrombin activity were measured in a fluorescent substrate and on
      coagulation by standard tests. Both paraoxon and obidoxime but not atropine
      significantly inhibited thrombin activity, and prolonged prothrombin time,
      thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were
      combined, a significant synergistic effect was found on both thrombin activity
      and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin
      activity and consequently alter the function of the coagulation system. Similar
      interactions may be clinically relevant for coagulation pathways in the blood and
      possibly in the brain.

PMID- 27689808
TI  - Assessing Urban Wastewater System Upgrades Using Integrated Modeling, Life Cycle
      Analysis, and Shadow Pricing.
AB  - This study assesses the environmental impacts of four measures proposed for
      upgrading of the urban wastewater system of Eindhoven and the Dommel River in The
      Netherlands, against the base case, "do-nothing" option. The measures aim to
      reduce the overall environmental impact of the Eindhoven urban wastewater system
      (UWS) by targeting river dissolved oxygen depletion and ammonia peaks, reducing
      combined sewer overflows, and enhancing nutrient removal. The measures are
      evaluated using a life cycle analysis with the boundaries including the receiving
      river section by means of an integrated model of the UWS. An uncertainty analysis
      of the estimated impacts has been performed to support the outcomes. The study
      also uses the economic concept of shadow prices to assign relative weights of
      socio-economic importance to the estimated life cycle impacts. This novel
      integration of tools complements the assessments of this UWS with the inclusion
      of long-term global environmental impacts and the investigation of trade-offs
      between different environmental impacts through a single monetary unit. The
      results support the selection of deeper clarifiers as the most environmentally
      beneficial measure for upgrade.

PMID- 27689807
TI  - Expression of microRNA-129-2-3p and microRNA-935 in plasma and brain tissue of
      human refractory epilepsy.
AB  - OBJECTIVE: Numerous microRNAs (miRNAs) are differentially expressed in specific
      diseases, suggesting possible use as diagnostic or prognostic biomarkers. The
      purpose of this study is to investigate the expression levels of miR-129-2-3p and
      miR-935 in cortical brain tissue and plasma samples from controls and refractory
      temporal lobe epilepsy (TLE) patients to evaluate the utility of these measures
      as diagnostic biomarkers. METHODS: The study was divided into three phases.
      First, cortical brain tissue samples from nine refractory TLE patients and eight
      controls were screened for differential miRNA expression using the Affymetrix
      miRNA 4.0 microarray. Second, real-time quantitative PCR (qRT-PCR) was used to
      verify the microarray results in brain tissue samples from 13 refractory TLE
      patients and 13 healthy controls (including those studied by microarray
      analysis). Third, we tested the expression levels of selected miRNAs in plasma
      samples from 25 refractory TLE patients and 25 healthy volunteers by qRT-PCR. The
      capacity of miR-129-2-3p and miR-935 expression to distinguish refractory TLE
      from health controls was tested by receiver operator characteristics (ROC) curve
      analysis. RESULTS: (1) High-resolution miRNA arrays indicated that miR-129-2-3p
      and miR-935 were significantly upregulated in the cortical brain tissues of TLE
      patients compared to controls. (2) qRT-PCR confirmed upregulated miR-129-2-3p
      expression in the brain tissue(P<0.0001) and plasma samples(P=0.0008) of
      refractory TLE patients. (3) The expression of miR-935 in epilepsy patients was
      higher than control group, however, there are no significant statistical
      differences between them whether in plasma samples(P=0.644) or in tissue
      samples(P=0.258). (4) ROC analysis of miRNA-129-2-3p showed that the area under
      the curve (AUC) was 0.929 (95% CI: 0.833-1.000; p=0.000) for brain tissue and
      0.778 (95% CI: 0.640-0.915; p=0.001) for plasma. CONCLUSION: Expression of miRNA
      129-2-3p was upregulated in cortical brain tissue and plasma samples from
      patients with refractory TLE, but miR-935 not. Plasma miRNA-129-2-3p has great
      potential as a non-invasive biomarker for early detection and clinical evaluation
      of refractory TLE.

PMID- 27689809
TI  - Age related normogram for antral follicle count in general population and
      comparison with previous studies.
AB  - OBJECTIVE: To construct antral follicle count (AFC) nomogram of general
      population for every age and to compare our data with previous studies to assess
      whether available AFC nomograms present any geographical inconsistency. STUDY
      DESIGN: A prospective cross-sectional study was conducted to document AFC
      nomogram among women in 20-50 years with regular menstrual bleeding. Patients
      admitted with hirsutism, menstrual irregularity, diagnosis of current/history of
      endometrioma and hormonal drug use within the last 6 months were excluded. For
      the final analysis, a total of 381 eligible women were recruited in which all
      scanning was performed in the early follicular phase. The 25th, 50th and 75th
      percentiles were compared with previous nomogram. RESULTS: The mean decrease of
      AFC in each year was 0.41. Among the age groups, there were no statistical
      significance between 20-24, 25-29 and 30-34, whereas decline in AFC was obvious
      after 35 years and beyond. The figures comparing our data and previous studies
      depicted similar steady decline at 25th, 50th and 75th percentiles. CONCLUSION:
      The current age related nomogram presented a steady decline in AFC that became
      significant after 35 years in otherwise healthy women with regular menstrual
      bleeding. Those percentiles might be used as a reference guide to point out the
      current status of ovarian reserve for a given woman. Additionally, producing
      nomogram might enforce using percentiles instead of constant thresholds to define
      various medical conditions such as polycystic ovarian morphology or diminished
      ovarian reserve. However, longitudinal data with larger sample size are still
      needed for the validation of those percentiles.

PMID- 27689810
TI  - The immune responses and expression of metallothionein (MT) gene and heat shock
      protein 70 (HSP 70) in juvenile rockfish, Sebastes schlegelii, exposed to
      waterborne arsenic (As3+).
AB  - Juvenile rockfish, Sebastes schlegelii (mean length 16.4+/-1.9cm, and mean weight
      71.6+/-6.4g) were exposed for 20days with the different levels of waterborne
      arsenic concentration (0, 50, 100, 200 and 400MUg/L). The plasma cortisol of S.
      schlegelii was significantly increased by the waterborne arsenit exposure. In the
      immune responses, the immunoglobulin M (Ig M) and lysozyme activity of S.
      schlegelii were significantly increased by the waterborne arsenic exposure. The
      acetylcholinesterase (AChE) activity of S. schlegelii was inhibited by the
      waterborne arsenic exposure. The substantial increases in the gene expression
      such as metallothionein (MT) and heat shock protein 70 (HSP 70) were observed by
      the waterborne arsenic exposure. The results demonstrated that waterborne arsenic
      exposure can induce the significant alterations in the immune responses and
      specific gene expression of S. schlegelii.

PMID- 27689811
TI  - Role of miR-199b-5p in regulating angiogenesis in mouse myocardial microvascular
      endothelial cells through HSF1/VEGF pathway.
AB  - Our study explored effects of miR-199b-5p on angiogenesis in mouse myocardial
      microvascular endothelial cells (MMVECs) and the involved working mechanisms. We
      applied explant culture to incubate C57/BL6 mouse MMVECs. Lipofection was used to
      transfect miR-199b-5p mimic, miR-199b-5p inhibitor and miR-199b-5p scramble
      respectively. MMVECs were divided into miR-199b-5p up-regulation, miR-199b-5p
      down-regulation and control groups based on above sequence. Expressions of miR
      199b-5p, heat shock factor protein 1 (HSF1) mRNA were assessed by real-time
      quantitative polymerase chain reaction (RT-QPCR). Expressions of HSF1 and
      vascular endothelial growth factor (VEGF) were assessed by Western Blotting. Cell
      proliferation was assessed by CCK8. Tubule formation assay was conducted to
      assess formation of blood vessels. Results showed that miR-199b-5p up/down
      regulation groups exhibited no obvious differences in the expressions of HSF1
      mRNA compared to control group. However, miR-199b-5p up-regulation group recorded
      lower expressions of HSF1 and VEGF in the level of protein, and reduced cell
      proliferation and tubule formation. Whereas, miR-199b-5p down-regulation group
      presented the contrary results. The experiment indicated that miR-199b-5p can
      regulate proliferation and angiogenesis in mouse MMVECs through the pathway of
      HSF1/VEGF.

PMID- 27689813
TI  - Conformational Change in the Mechanism of Inclusion of Ketoprofen in beta
      Cyclodextrin: NMR Spectroscopy, Ab Initio Calculations, Molecular Dynamics
      Simulations, and Photoreactivity.
AB  - Inclusion of drugs in cyclodextrins (CDs) is a recognized tool for modifying
      several properties such as solubility, stability, bioavailability, and so on. The
      photoreactive behavior of the beta-CD/ketoprofen (KP) complex upon UV exposure
      showed a significant increase in photodecarboxylation, whereas the secondary
      degradation products by hydroxylation of the benzophenone moiety were inhibited.
      The results may account for an improvement of KP photophysical properties upon
      inclusion, thus better fostering its topical use. To correlate the structural
      details of the inclusion with these results, an NMR spectroscopic study of KP
      upon inclusion in beta-CD was performed. Effects of the magnetically anisotropic
      centers of KP, changing their orientations upon inclusion and giving chemical
      shift variations, were specifically correlated with the results of the molecular
      dynamic simulations and ab initio calculations. In the large variety of papers
      focusing on the structural analysis of beta-CD complexes, this work represents
      one of the few examples in which a detailed analysis of these simultaneous
      upfield-downfield NMR shifts of the same aromatic molecule upon inclusion is
      reported. Interestingly, the results demonstrate that the observed upfield and
      downfield shifts upon inclusion are not related to any direct magnetic role of
      beta-CD. The conformational change of KP upon the inclusion process consists of a
      slight reduction in the angle between the two phenyl rings and in a remarkable
      reduction in the mobility of the carboxyl group, the latter being one of the main
      contributions to the NMR resonance shifts. These structural details help in
      understanding the features of the inclusion complex and, eventually, the driving
      force for its formation.

PMID- 27689812
TI  - Cryo-EM in the study of challenging systems: the human transcription pre
      initiation complex.
AB  - Single particle cryo-Electron Microscopy (cryo-EM) is a technique that allows the
      structural characterization of macromolecules without the need for
      crystallization. For certain type of samples that are ideally suited for cryo-EM
      studies it has been possible to reach high-resolution structures following
      relatively standard procedures. Other biological systems remain highly
      challenging, even for cryo-EM. Challenges may involve the scarcity of the sample,
      poor stability of the complexes, and most often, the intrinsic flexibility of
      biological molecules. Among these challenging samples are large eukaryotic
      transcription complexes, which suffer from all such shortcomings. Here we report
      how we have recently tried to overcome those challenges in order to improve our
      structural understanding of the human transcription pre-initiation complex
      assembly and the transcription initiation process. Parallel efforts have also
      been carried out for budding yeast transcription initiation complexes, allowing
      comparisons that establish both the overall conservation and the specific
      structural differences between the two systems.

PMID- 27689804
TI  - Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions.
AB  - Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful
      methods to synthesize anilines and aniline derivatives, an important class of
      compounds throughout chemical research. A key factor in the widespread adoption
      of these methods has been the continued development of reliable and versatile
      catalysts that function under operationally simple, user-friendly conditions.
      This review provides an overview of Pd-catalyzed N-arylation reactions found in
      both basic and applied chemical research from 2008 to the present. Selected
      examples of C-N cross-coupling reactions between nine classes of nitrogen-based
      coupling partners and (pseudo)aryl halides are described for the synthesis of
      heterocycles, medicinally relevant compounds, natural products, organic
      materials, and catalysts.

PMID- 27689814
TI  - Heparan sulfates and the decrease of N-glycans promote early adipogenic
      differentiation rather than myogenesis of murine myogenic progenitor cells.
AB  - In vitro, extracted muscle satellite cells, called myogenic progenitor cells, can
      differentiate either in myotubes or preadipocytes, depending on environmental
      factors and the medium. Transcriptomic analyses on glycosylation genes during
      satellite cells differentiation into myotubes showed that 31 genes present a
      significant variation of expression at the early stages of murine myogenic
      progenitor cells (MPC) differentiation. In the present study, we analyzed the
      expression of 383 glycosylation related genes during murine MPC differentiation
      into preadipocytes and compared the data to those previously obtained during
      their differentiation into myotubes. Fifty-six glycosylation related genes are
      specifically modified in their expression during early adipogenesis. The
      variations correspond mainly to: a decrease of N-glycans, and of alpha (2,3) and
      (2,6) linked sialic acids, and to a high level of heparan sulfates. A high amount
      of TGF-beta1 in extracellular media during early adipogenesis was also observed.
      It seems that the increases of heparan sulfates and TGF-beta1 favor pre
      adipogenic differentition of MPC and possibly prevent their myogenic
      differentiation.

PMID- 27689815
TI  - Motor cortical dysfunction develops in spinocerebellar ataxia type 3.
AB  - OBJECTIVE: Spinocerebellar ataxia type 3 (SCA3) is an inherited neurodegenerative
      disorder characterized by cerebellar ataxia and variable expression of clinical
      features beyond the cerebellum. To gain further insights into disease
      pathophysiology, the present study explored motor cortex function in SCA3 to
      determine whether cortical dysfunction was present and if this contributed to the
      development of clinical manifestations. METHODS: Clinical phenotyping and
      longitudinal assessments were combined with central (threshold-tracking
      transcranial magnetic stimulation) and peripheral (nerve excitability) techniques
      in 11 genetically characterized SCA3 patients. RESULTS: Short-interval
      intracortical inhibition was significantly reduced in presymptomatic and
      symptomatic SCA3 patients (-1.3+/-1.4%) compared to healthy controls (10.3+/
      0.7%, P<0.0005), with changes evident prior to clinical onset of ataxia and
      related to worsening severity (R=-0.78, P<0.005). Central motor conduction time
      was also significantly prolonged in presymptomatic and symptomatic SCA3 patients
      (7.5+/-0.4ms) compared to healthy controls (5.3+/-0.2ms, P<0.0005) and related to
      clinical severity (R=0.81, P<0.005). Markers of peripheral motor
      neurodegeneration and excitability did not correlate with cortical
      hyperexcitability or ataxia. CONCLUSIONS: Simultaneous investigation of clinical
      status, and central and peripheral nerve function has identified progressive
      cortical dysfunction in SCA3 patients related to the development of ataxia.
      SIGNIFICANCE: These findings suggest alteration in cortical activity is
      associated with SCA3 pathogenesis and neurodegeneration.

PMID- 27689816
TI  - Voltage-Rectified Current and Fluid Flow in Conical Nanopores.
AB  - Ion current rectification (ICR) refers to the asymmetric potential-dependent rate
      of the passage of solution ions through a nanopore, giving rise to electrical
      current-voltage characteristics that mimic those of a solid-state electrical
      diode. Since the discovery of ICR in quartz nanopipettes two decades ago,
      synthetic nanopores and nanochannels of various geometries, fabricated in
      membranes and on wafers, have been extensively investigated to understand
      fundamental aspects of ion transport in highly confined geometries. It is now
      generally accepted that ICR requires an asymmetric electrical double layer within
      the nanopore, producing an accumulation or depletion of charge-carrying ions at
      opposite voltage polarities. Our research groups have recently explored how the
      voltage-dependent ion distributions and ICR within nanopores can induce novel
      nanoscale flow phenomena that have applications in understanding ionics in porous
      materials used in energy storage devices, chemical sensing, and low-cost
      electrical pumping of fluids. In this Account, we review our most recent
      investigations on this topic, based on experiments using conical nanopores (10
      300 nm tip opening) fabricated in thin glass, mica, and polymer membranes.
      Measurable fluid flow in nanopores can be induced either using external pressure
      forces, electrically via electroosmotic forces, or by a combination of these two
      forces. We demonstrate that pressure-driven flow can greatly alter the electrical
      properties of nanopores and, vice versa, that the nonlinear electrical properties
      of conical nanopores can impart novel and useful flow phenomena. Electroosmotic
      flow (EOF), which depends on the magnitude of the ion fluxes within the double
      layer of the nanopore, is strongly coupled to the accumulation/depletion of ions.
      Thus, the same underlying cause of ICR also leads to EOF rectification, i.e.,
      unequal flows occurring for the same voltage but opposite polarities. EOF
      rectification can be used to electrically pump fluids with very precise control
      across membranes containing conical pores via the application of a symmetric
      sinusoidal voltage. The combination of pressure and asymmetric EOF can also
      provide a means to generate new nanopore electrical behaviors, including negative
      differential resistance (NDR), in which the current through a conical pore
      decreases with increasing driving force (applied voltage), similar to solid-state
      tunnel diodes. NDR results from a positive feedback mechanism between the ion
      distributions and EOF, yielding a true bistability in both fluid flow and
      electrical current at a critical applied voltage. Nanopore-based NDR is extremely
      sensitive to the surface charge near the nanopore opening, suggesting possible
      applications in chemical sensing.

PMID- 27689817
TI  - A Single Electron Transfer (SET) Approach to C-H Amidation of Hydrazones via
      Visible-Light Photoredox Catalysis.
AB  - The reductive single electron transfer (SET) umpolung amination of aldehyde
      derived hydrazones has been developed through visible-light-promoted photoredox
      catalysis. The ideal transformation of hydrazones into the corresponding
      hydrazonamide through selective carbon-hydrogen (C-H) bond functionalization
      represents one of the most step- and atom-economical methods. This SET umpolung
      strategy features mild conditions and a remarkably broad substrate scope,
      offering an entirely new substrate class to direct C-H amination.

PMID- 27689818
TI  - Supercapattery Based on Binder-Free Co3(PO4)2.8H2O Multilayer Nano/Microflakes on
      Nickel Foam.
AB  - A binder-free cobalt phosphate hydrate (Co3(PO4)2.8H2O) multilayer
      nano/microflake structure is synthesized on nickel foam (NF) via a facile
      hydrothermal process. Four different concentrations (2.5, 5, 10, and 20 mM) of
      Co2+ and PO4-3 were used to obtain different mass loading of cobalt phosphate on
      the nickel foam. The Co3(PO4)2.8H2O modified NF electrode (2.5 mM) shows a
      maximum specific capacity of 868.3 C g-1 (capacitance of 1578.7 F g-1) at a
      current density of 5 mA cm-2 and remains as high as 566.3 C g-1 (1029.5 F g-1) at
      50 mA cm-2 in 1 M NaOH. A supercapattery assembled using Co3(PO4)2.8H2O/NF as the
      positive electrode and activated carbon/NF as the negative electrode delivers a
      gravimetric capacitance of 111.2 F g-1 (volumetric capacitance of 4.44 F cm-3).
      Furthermore, the device offers a high specific energy of 29.29 Wh kg-1 (energy
      density of 1.17 mWh cm-3) and a specific power of 4687 W kg-1 (power density of
      187.5 mW cm-3).

PMID- 27689819
TI  - Block Copolymer-Assisted Solvothermal Synthesis of Hollow Bi2MoO6 Spheres
      Substituted with Samarium.
AB  - Hollow spherical structures of ternary bismuth molybdenum oxide doped with
      samarium (Bi2-xSmxMoO6) were successfully synthesized via development of a
      Pluronic P123 (PEO20-PPO70-PEO20)-assisted solvothermal technique. Density
      functional theory calculations have been performed to improve our understanding
      of the effects of Sm doping on the electronic band structure, density of states,
      and band gap of the material. The calculations for 0 <= x <= 0.3 revealed a
      considerably flattened conduction band minimum near the Gamma point, suggesting
      that the material can be considered to possess a quasi-direct band gap. In
      contrast, for x = 0.5, the conduction band minimum is deflected toward the U
      point, making it a distinctly indirect band gap material. The effects of a hollow
      structure as well as Sm substitution on the absorbance and fluorescence
      properties of the materials produced increased emission intensities at low Sm
      concentrations (x = 0.1 and 0.3), with x = 0.1 displaying a peak
      photoluminescence intensity 13.2 times higher than for the undoped bulk sample.
      Subsequent increases in the Sm concentration resulted in quenching of the
      emission intensity, indicative of the onset of a quasi-direct-to-indirect
      electronic band transition. These results indicate that both mesoscale
      structuring and Sm doping will be promising routes for tuning optoelectronic
      properties for future applications such as catalysis and photocatalysis.

PMID- 27689820
TI  - Kinetics of Excited Oxygen Formation in Shock-Heated O2-Ar Mixtures.
AB  - The formation of electronically excited atomic oxygen was studied behind
      reflected shock waves using cavity-enhanced absorption spectroscopy. Mixtures of
      1% O2-Ar were shock-heated to 5400-7500 K, and two distributed-feedback diode
      lasers near 777.2 and 844.6 nm were used to measure time-resolved populations of
      atomic oxygen's 5S degrees  and 3S degrees  electronic states, respectively.
      Measurements were compared with simulated population time histories obtained
      using two different kinetic models that accounted for thermal nonequilibrium
      effects: (1) a multitemperature model and (2) a reduced collisional-radiative
      model. The former assumed a Boltzmann distribution of electronic energy, whereas
      the latter allowed for non-Boltzmann populations by treating the probed
      electronic states as pseudospecies and accounting for dominant electronic
      excitation/de-excitation processes. The effects of heavy-particle collisions were
      investigated and found to play a major role in the kinetics of O atom electronic
      excitation at the conditions studied. For the first time, rate constants (kM) for
      O atom electronic excitation from the ground state (3P) due to collisions with
      argon atoms were directly inferred using the reduced collisional-radiative model,
      kM(3P -> 5S degrees ) = 7.8 * 10-17T0.5 exp(-1.061 * 105K/T) +/- 25% cm3 s-1 and
      kM(3P -> 3S degrees ) = 2.5 * 10-17T0.5 exp(-1.105 * 105K/T) +/- 25% cm3 s-1.

PMID- 27689823
TI  - A Strong Case for Prudent School Siting: The West Fertilizer Company Explosion.

PMID- 27689822
TI  - Transcriptomic profiles of the upper olfactory rosette in cultured and wild
      Senegalese sole (Solea senegalensis) males.
AB  - The aims of this study were the characterization of the upper olfactory
      epithelium of cultured and wild Senegalese sole mature males at histological and
      transcriptomic (using RNA-Seq) level. No significant differences in tissue
      structure, cell types and cellular distribution pattern (olfactory sensory
      neurons) were identified between cultured and wild specimens. Deep transcriptomic
      analysis showed 2387 transcripts were differentially expressed between cultured
      and wild groups. A detailed analysis identified the differentially expressed
      transcripts included some olfactory receptors (OR, TAAR and V2R-like) and
      transcripts related with the control of reproduction such as the brain aromatase
      cytochrome P450 and tachykinin-3. Also a wide set of genes related with lipid
      sensing, metabolism and transport were differentially expressed and these
      transcripts were often down-regulated in cultured fish. Furthermore, cultured
      males presented a higher expression of genes related with goblet cells and mucin
      production that modulates innate and adaptive immune responses. All these changes
      in gene expression could be explained by different nutritional status and diet
      preference. The different expression of transcripts related to olfaction,
      reproduction, nutrient sensing and immune system demonstrate distinct differences
      in functionalities between cultured and wild soles providing new clues about the
      sexual dysfunction in this species.

PMID- 27689821
TI  - High-Valent Manganese-Oxo Valence Tautomers and the Influence of Lewis/Bronsted
      Acids on C-H Bond Cleavage.
AB  - The addition of Lewis or Bronsted acids (LA = Zn(OTf)2, B(C6F5)3, HBArF, TFA) to
      the high-valent manganese-oxo complex MnV(O)(TBP8Cz) results in the stabilization
      of a valence tautomer MnIV(O-LA)(TBP8Cz*+). The ZnII and B(C6F5)3 complexes were
      characterized by manganese K-edge X-ray absorption spectroscopy (XAS). The
      position of the edge energies and the intensities of the pre-edge (1s to 3d)
      peaks confirm that the Mn ion is in the +4 oxidation state. Fitting of the
      extended X-ray absorption fine structure (EXAFS) region reveals 4 N/O ligands at
      Mn-Nave = 1.89 A and a fifth N/O ligand at 1.61 A, corresponding to the terminal
      oxo ligand. This Mn-O bond length is elongated compared to the MnV(O) starting
      material (Mn-O = 1.55 A). The reactivity of MnIV(O-LA)(TBP8Cz*+) toward C-H
      substrates was examined, and it was found that H* abstraction from C-H bonds
      occurs in a 1:1 stoichiometry, giving a MnIV complex and the dehydrogenated
      organic product. The rates of C-H cleavage are accelerated for the MnIV(O
      LA)(TBP8Cz*+) valence tautomer as compared to the MnV(O) valence tautomer when LA
      = ZnII, B(C6F5)3, and HBArF, whereas for LA = TFA, the C-H cleavage rate is
      slightly slower than when compared to MnV(O). A large, nonclassical kinetic
      isotope effect of kH/kD = 25-27 was observed for LA = B(C6F5)3 and HBArF,
      indicating that H-atom transfer (HAT) is the rate-limiting step in the C-H
      cleavage reaction and implicating a potential tunneling mechanism for HAT. The
      reactivity of MnIV(O-LA)(TBP8Cz*+) toward C-H bonds depends on the strength of
      the Lewis acid. The HAT reactivity is compared with the analogous corrole complex
      MnIV(O-H)(tpfc*+) recently reported (J. Am. Chem. Soc. 2015, 137, 14481-14487).

PMID- 27689824
TI  - Effects of Intermolecular Charge Transfer in Liquid Water on Raman Spectra.
AB  - The low-frequency vibrational spectrum of liquid water is composed of
      contributions from the intermolecular librational and translation modes. The
      existence of these two modes introduces difficulty into the simulation of
      experimentally obtained Raman spectra. We constructed a polarizability function
      for a water model that includes intramolecular charge flow (CF) effects,
      intermolecular charge transfer (CT) effects, and intermolecular dipole-induced
      dipole (DID) effects. We computed the one-dimensional (1D) Raman and terahertz
      (THz) spectra with all of these effects included (CFCT-DID) and compared with
      experimental spectra. We find that the CFCT-DID function provides a better
      description of the experimental results, because the CT effects reduce the
      polarizability only for translational motion to which parallelly polarized (VV)
      and perpendicularly polarized (VH) Raman spectra are sensitive. In our
      calculations of two-dimensional (2D) Raman and THz-Raman spectra, we observe the
      enhancement of echo signals in both cases. The details of the CFCT-DID function,
      along with its source code, are provided in the Supporting Information.

PMID- 27689826
TI  - Natpara for the treatment of hypoparathyroidism.
AB  - INTRODUCTION: Hypoparathyroidism is a rare endocrine disorder characterized by
      hypocalcaemia and hyperphosphatemia, due to absent or inappropriately low
      parathyroid hormone levels. For management of chronic hypoparathyroidism, current
      treatment options involve oral calcium and vitamin D. This standard treatment
      cannot resolve all problematic aspects of the disease, such as abnormal bone
      remodeling and reduced quality of life, and is associated with long-term
      complications, including nephrolithiasis, nephrocalcinosis, renal impairment,
      cataracts and cerebral calcifications. AREAS COVERED: In 2015, the FDA (Food and
      Drug Administration) approved rhPTH (1-84), named Natpara(r), a bioengineered
      recombinant human PTH, for the management of hypoparathyroidism of any etiology,
      except Autosomal Dominant Hypocalcemia, not well controlled with calcium and
      active vitamin D. Herein, the authors review its chemistry, pharmacodynamics,
      pharmacokinetics and clinical efficacy for hypoparathyroidism. EXPERT OPINION:
      Replacement therapy with rhPTH (1-84) is a fundamental step in the treatment of
      chronic hypoparathyroidism in cases not well controlled by standard therapy,
      providing the natural hormone that is lacking for the maintenance of normal
      calcium levels, and reducing long-term risks associated with conventional
      therapy. Nevertheless, given the chronic nature of the disease, in the future,
      further studies will have to be performed to evaluate long-term efficacy and
      safety of the drug.

PMID- 27689825
TI  - Inhibin A and inhibin B producing ovarian fibrothecoma revealed by suppression of
      follicle stimulating hormone (FSH) in a post-menopausal woman: report of the
      first case.
AB  - In this report, we describe the first case ever reported in the literature, of an
      inhibin-A (INHA) and inhibin-B (INHB) producing fibrothecoma. A post-menopausal
      woman was referred to our unit because of follicle stimulating hormone (FSH)
      level below the reference interval for postmenopausal women. By contrast
      luteinizing hormone, hCG, and estradiol levels were within normal range. This
      discrepancy suggested the secretion of FSH inhibitory factors. INHB and INHA
      levels were markedly elevated for age, 475 pg/mL and 100 pg/mL, respectively.
      Ultrasonography and MRI showed a pelvic mass of indeterminate nature. Abnormal
      inhibin secretion is generally observed in granulosa cell tumors. In this case
      this etiology was unlikely because of low estradiol and AMH levels. Surgical
      exploration revealed a 10 cm mass of the left ovary proven histologically to be
      an ovarian fibrothecoma (OFT). After tumor removal, INHB and INHA levels
      decreased rapidly. Only three cases of OFT with an important secretion of INHB
      have been reported to date. INHA secretion has never been associated with OFT.
      There is a need to develop coupled hormone and imaging strategies to diagnose the
      source of INH secretion in case of FSH/LH discrepancy.

PMID- 27689827
TI  - Development of a P((MAA-co-NVP)-g-EG) Hydrogel Platform for Oral Protein
      Delivery: Effects of Hydrogel Composition on Environmental Response and Protein
      Partitioning.
AB  - Hydrogels based upon terpolymers of methacrylic acid, N-vinyl pyrrolidone, and
      poly(ethylene glycol) are developed and characterized for their ability to
      respond to changes in environmental pH and to partition protein therapeutics of
      varying molecular weights and isoelectric points. P((MAA-co-NVP)-g-EG) hydrogels
      are synthesized with PEG-based cross-linking agents of varying length and
      incorporation densities. The composition is confirmed using FT-IR spectroscopy
      and shows peak shifts indicating hydrogen bonding. Scanning electron microscopy
      reveals microparticles with an irregular, planar morphology. The pH-responsive
      behavior of the hydrogels is confirmed under equilibrium and dynamic conditions,
      with the hydrogel collapsed at acidic pH and swollen at neutral pH. The ability
      of the hydrogels to partition model protein therapeutics at varying pH and ionic
      strength is evaluated using three model proteins: insulin, porcine growth
      hormone, and ovalbumin. Finally, the microparticles are evaluated for adverse
      interactions with two model intestinal cell lines and show minimal cytotoxicity
      at concentrations below 5 mg mL-1 .

PMID- 27689828
TI  - Metabolic Fate of Branched-Chain Amino Acids During Adipogenesis, in Adipocytes
      From Obese Mice and C2C12 Myotubes.
AB  - Branched-chain amino acid (BCAA) catabolism is regulated by the branched-chain
      aminotransferase (BCAT2) and the branched-chain alpha-keto acid dehydrogenase
      complex (BCKDH). BCAT2 and BCKDH expression and activity are modified during
      adipogenesis and altered in adipose tissues of mice with genetic or diet-induced
      obesity. However, little is known about how these modifications and alterations
      affect the intracellular metabolic fate of BCAAs during adipogenesis, in
      adipocytes from mice fed a control or high-fat diet or in C2C12 myotubes. Here,
      we demonstrate that BCAAs are mainly incorporated into proteins during the early
      stages of adipocyte differentiation. However, they are oxidized and incorporated
      into lipids during the late days of differentiation. Conversely, 92% and 97% of
      BCAA were oxidized, 1.6% and 6% were used for protein synthesis and 1.2% and 1.5%
      were incorporated into lipids in adipocytes from epididymal and subcutaneous
      adipose tissue, respectively. All three pathways were decreased in adipocytes
      from mice fed a high-fat diet. In C2C12 myotubes, leucine is mainly used for
      protein synthesis and palmitate is incorporated into lipids. Interestingly,
      leucine decreased both palmitate oxidation and its incorporation to lipids and
      proteins; and palmitate increased leucine oxidation and decreased its
      incorporation to lipids and proteins in a dose-dependent manner. These results
      demonstrate that BCAA metabolic fate differs between the early and late stages of
      adipocyte differentiation and in adipocytes from mice fed a control or high-fat
      diet; and that leucine affects the metabolic fate of palmitate and vice versa in
      C2C12 myotubes. J. Cell. Biochem. 118: 808-818, 2017. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27689829
TI  - Chronic, intractable nodules after filler injection successfully treated with a
      bipolar radiofrequency device.

PMID- 27689831
TI  - Noninvasive Physiologic Vascular Studies: A Guide to Diagnosing Peripheral
      Arterial Disease.
AB  - Noninvasive physiologic vascular studies play an important role in the diagnosis
      and characterization in peripheral arterial disease (PAD) of the lower extremity.
      These studies evaluate the physiologic parameters of blood flow through segmental
      arterial pressures, Doppler waveforms, and pulse volume recordings. Collectively,
      they comprise a powerful toolset for defining the functionality of the arterial
      system, localizing the site of disease, and providing prognostic data. This
      technology has been widely adopted by diverse medical specialty practitioners,
      including radiologists, surgeons, cardiologists, and primary care providers. The
      use of these studies increased substantially between 2000 and 2010. Although they
      do not employ imaging, they remain a critical component for a comprehensive
      radiologic vascular laboratory. A strong presence of radiology in the diagnosis
      of PAD adds value in that radiologists have shifted to noninvasive alternatives
      to diagnostic catheter angiography (DCA), such as computed tomography (CT) and
      magnetic resonance (MR) angiography, which provide a more efficient, less
      expensive, and lower-risk alternative. Other specialties have increased the use
      of DCA during the same period. The authors provide a review of the relevant
      anatomy and physiology of PAD as well as the associated clinical implications. In
      addition, guidelines for interpreting the ankle-brachial index, segmental
      pressures, Doppler waveforms, and pulse volume recordings are reviewed as well as
      potential limitations of these studies. Noninvasive physiologic vascular studies
      are provided here for review with associated correlating angiographic, CT, and/or
      MR findings covering the segmental distribution of PAD as well as select
      nonatherosclerotic diagnoses. (c)RSNA, 2016.

PMID- 27689830
TI  - RGD targeting of human ferritin iron oxide nanoparticles enhances in vivo MRI of
      vascular inflammation and angiogenesis in experimental carotid disease and
      abdominal aortic aneurysm.
AB  - PURPOSE: To evaluate Arg-Gly-Asp (RGD)-conjugated human ferritin (HFn) iron oxide
      nanoparticles for in vivo magnetic resonance imaging (MRI) of vascular
      inflammation and angiogenesis in experimental carotid disease and abdominal
      aortic aneurysm (AAA). MATERIALS AND METHODS: HFn was genetically engineered to
      express the RGD peptide and Fe3 O4 nanoparticles were chemically synthesized
      inside the engineered HFn (RGD-HFn). Macrophage-rich left carotid lesions were
      induced by ligation in FVB mice made hyperlipidemic and diabetic (n = 14), with
      the contralateral right carotid serving as control. Murine AAAs were created by
      continuous angiotensin II infusion in ApoE-deficient mice (n = 12), while control
      mice underwent saline infusion (n = 8). All mice were imaged before and after
      intravenous injection with either RGD-HFn-Fe3 O4 or HFn-Fe3 O4 using a gradient
      echo sequence on a whole-body 3T clinical scanner, followed by histological
      analysis. The nanoparticle accumulation was assessed by the extent of T2*-induced
      carotid lumen reduction (% lumen loss) or aortic T2*-weighted signal intensity
      reduction (% SI [signal intensity] loss). RESULTS: RGD-HFn-Fe3 O4 was taken up
      more than HFn-Fe3 O4 in both the ligated left carotid arteries (% lumen loss; 69
      +/- 9% vs. 36 +/- 7%, P = 0.01) and AAAs (% SI loss; 47 +/- 6% vs. 20 +/- 5%, P =
      0.01). The AAA % SI loss correlated positively with AAA size (r = 0.89, P <
      0.001). Histology confirmed the greater accumulation and colocalization of RGD
      HFn-Fe3 O4 to both vascular macrophages and endothelial cells. CONCLUSION: RGD
      HFn-Fe3 O4 enhances in vivo MRI by targeting both vascular inflammation and
      angiogenesis, and provides a promising translatable MRI approach to detect high
      risk atherosclerotic and aneurysmal vascular diseases. LEVEL OF EVIDENCE: 1 J.
      Magn. Reson. Imaging 2017;45:1144-1153.

PMID- 27689832
TI  - Invited Commentary on "Elastography in Chronic Liver Disease".

PMID- 27689834
TI  - AAGFO Distinguished Member Award.

PMID- 27689836
TI  - Blue-Light Transmittance of Esthetic Monolithic CAD/CAM Materials With Respect to
      Their Composition, Thickness, and Curing Conditions.
AB  - Determining the amount of blue light (360-540nm) passing through nine monolithic
      computer-aided design/computer-aided manufacturing (CAD/CAM) materials depends on
      material thickness, initial irradiance, and the distance between the curing unit
      and the specimen's surface. A total of 180 specimens of two thicknesses (1 mm and
      2 mm, n=10/subgroup) were fabricated from TelioCAD, VITA CAD-Temp (VCT),
      experimental nanocomposite, LAVA Ultimate (LU), VITA ENAMIC (VE), VITA MarkII
      (VM), IPS EmpressCAD (IEC), IPS e.maxCAD (IEM), and CELTRA DUO (CD). The
      irradiance passing through the CAD/CAM materials and thicknesses was measured
      using a light-emitting-diode curing unit with standard-power, high-power, and
      plasma modes by means of a USB4000 spectrometer. The curing unit was placed
      directly on the specimen's surface at 2- and 4-mm distances from the specimen's
      surface. Data were analyzed using a multivariate analysis and one-way analysis of
      variance with the post hoc Scheffe test (p<0.05). The highest transmitted
      irradiance was measured for VM and LU, followed by VCT and IEC, while the lowest
      values showed VE, followed by IEM and CD. The highest transmitted irradiance was
      recorded by exposing the material to the plasma mode, followed by the high- and
      standard-power modes. The measured irradiance was decreased by increasing the
      specimen's thickness from 1 to 2 mm. Fewer differences were measured when the
      curing unit was placed at 0 or 2 mm from the specimen's surface, and the
      irradiance passing through the specimens was lower at a distance of 4 mm.

PMID- 27689838
TI  - Faculty Posting.

PMID- 27689837
TI  - Microleakage of Lithium Disilicate Crown Margins Finished on Direct Restorative
      Materials.
AB  - OBJECTIVE: For some esthetic clinical situations, it is necessary to finish crown
      margins on direct restorative materials to preserve tissue integrity, bonding
      integrity, and biological width. The purpose of this research was to investigate
      microleakage at the interface between bonded lithium disilicate crowns and
      various direct restorative materials in a class III and class V position. METHODS
      AND MATERIALS: Class III or class V restorations were prepared on one side of
      extracted incisors with either Tetric EvoCeram, Tetric Evoceram Bulk, Fuji II LC,
      or Tetric Evoflow. The teeth were prepared for and received a lithium disilicate
      crown. After load fatiguing, the specimens were thermo-cycled with a fuchsin dye
      and sectioned. The depth and area of dye penetration were measured with a
      dimensional grid in micrometers using stereomicroscopy and reported as mean dye
      depth and area (MUm) +/- SD. The comparison of multiple categorical independent
      variables with ratio scale dependent variables was evaluated with an analysis of
      variance and Tukey's post hoc analysis. RESULTS: A statistically significant
      higher dye penetration was noted for all treatment groups compared with the
      positive control (side opposite the restoration after sagittal sectioning was
      used as positive control) regardless of material or placement area (p<0.05). In
      comparing treatment groups, the Tetric EvoFlow experienced a statistically higher
      dye penetration than did the other treatment groups regardless of material or
      placement area (p<0.05). There was no statistically significant difference
      between the Tetric EvoCeram, Tetric Evoceram Bulk, and Fuji II LC materials
      regardless of placement area (p>0.05). CONCLUSIONS: Within the limitations of
      this study, it can be concluded that flowable composite materials as finish lines
      that interact with resin cements could lead to exacerbated interfacial
      degradation. Finishing lithium disilicate all-ceramic crowns on flowable resin
      composite materials in the esthetic zone should be used with caution. If
      necessary, finishing lithium disilicate all-ceramic crowns on nanofilled resin
      composite or resin-modified glass ionomer materials seems to provide the least
      dye penetration depth and area.

PMID- 27689833
TI  - Elastography in Chronic Liver Disease: Modalities, Techniques, Limitations, and
      Future Directions.
AB  - Chronic liver disease has multiple causes, many of which are increasing in
      prevalence. The final common pathway of chronic liver disease is tissue
      destruction and attempted regeneration, a pathway that triggers fibrosis and
      eventual cirrhosis. Assessment of fibrosis is important not only for diagnosis
      but also for management, prognostic evaluation, and follow-up of patients with
      chronic liver disease. Although liver biopsy has traditionally been considered
      the reference standard for assessment of liver fibrosis, noninvasive techniques
      are the emerging focus in this field. Ultrasound-based elastography and magnetic
      resonance (MR) elastography are gaining popularity as the modalities of choice
      for quantifying hepatic fibrosis. These techniques have been proven superior to
      conventional cross-sectional imaging for evaluation of fibrosis, especially in
      the precirrhotic stages. Moreover, elastography has added utility in the follow
      up of previously diagnosed fibrosis, the assessment of treatment response,
      evaluation for the presence of portal hypertension (spleen elastography), and
      evaluation of patients with unexplained portal hypertension. In this article, a
      brief overview is provided of chronic liver disease and the tools used for its
      diagnosis. Ultrasound-based elastography and MR elastography are explored in
      depth, including a brief glimpse into the evolution of elastography. Elastography
      is based on the principle of measuring tissue response to a known mechanical
      stimulus. Specific elastographic techniques used to exploit this principle
      include MR elastography and ultrasonography-based static or quasistatic strain
      imaging, one-dimensional transient elastography, point shear-wave elastography,
      and supersonic shear-wave elastography. The advantages, limitations, and pitfalls
      of each modality are emphasized. (c)RSNA, 2016.

PMID- 27689839
TI  - Epub Clinical Relevance Statements.

PMID- 27689840
TI  - Water Sorption and Solubility of Luting Agents Used Under Ceramic Laminates With
      Different Degrees of Translucency.
AB  - PURPOSE: The aim of this study was to evaluate the effect of low-thickness
      ceramic laminate translucency on water sorption and solubility in resin luting
      agents. METHODS AND MATERIALS: Ceramic slides (15*0.7 mm) were generated using
      lithium disilicate (IPS e.max Press, Ivoclar-Vivadent, Schaan, Liechtenstein)
      that were A1 in color and had decreasing degrees of translucency (high, medium,
      and low). A slide of transparent glass of similar size was used as the control.
      Under each slide, 15 specimens (8*0.5 mm) of differing composite materials from
      the same manufacturer (3M ESPE Dental Products, St Paul, MN, USA) were prepared
      (n=5): light-cured resin cement (RelyX Veneer); dual-cured resin cement (RelyX
      ARC); and flowable composite (Z350XT Flow). To evaluate the loss or gain of mass,
      the specimens were dried until a constant mass was reached. Then, they were
      immersed in water for seven days and weighed immediately following removal from
      water. Subsequently, the specimens were dried again until a constant mass was
      obtained. The mass measurements were used to calculate the water sorption and
      solubility. Statistical analyses were carried out using a two-way analysis of
      variance and the Tukey test. RESULTS: Under the high-translucency ceramic slides,
      all of the luting agents showed similar performance regarding water sorption; the
      flowable composite resin and the light-cured resin cement had the lowest
      solubility values. Under the medium- and low-translucency surfaces, the dual
      cured resin cement and the flowable composite resin showed better performance
      with respect to water sorption and solubility. CONCLUSIONS: In the case of high
      translucency laminates, luting agents with different activation methods might be
      used. However, even in thin sections, decreasing the translucency of the laminate
      led to significant loss of light penetration, indicating a decreased likelihood
      of the physical activation of the resin cement.

PMID- 27689841
TI  - Fractographical Analysis and Biomechanical Considerations of a Tooth Restored
      With Intracanal Fiber Post: Report of the Fracture and Importance of the Fiber
      Arrangements.
AB  - OBJECTIVE: This article aims to present a fractographic analysis of an anterior
      tooth restored with a glass fiber post with parallel fiber arrangement, taking
      into account force vectors, finite element analysis, and scanning electron
      microscopy (SEM). METHODS: A patient presented at the Faculty of Dentistry
      (Federal University of Santa Maria, Brazil) with an endodontically treated tooth
      (ETT), a lateral incisor that had a restorable fracture. The treatment was
      performed, and the fractured piece was analyzed using stereomicroscopy, SEM, and
      finite element analysis. RESULTS: The absence of remaining coronal tooth
      structure might have been the main factor for the clinical failure. We observed
      different stresses actuating in an ETT restored with a fiber post as well as
      their relationship with the ultimate fracture. Tensile, compression, and shear
      stresses presented at different levels inside the restored tooth. Tensile and
      compressive stresses acted together and were at a maximum in the outer portions
      and a minimum in the inner portions. In contrast, shear stresses acted
      concomitantly with tensile and compressive stresses. Shear was higher in the
      inner portions (center of the post), and lower in the outer portions. This was
      confirmed by finite element analysis. The SEM analysis showed tensile and
      compression areas in the fiber post (exposed fibers=tensile areas=lingual
      surface; nonexposed fibers=compression areas=buccal surface) and shear areas
      inside the post (scallops and hackle lines). Stereomicroscopic analysis showed
      brown stains in the crown/root interface, indicating the presence of microleakage
      (tensile area=lingual surface). CONCLUSION: We concluded that glass fiber posts
      with parallel fibers (0 degrees ), when restoring anterior teeth, present a
      greater fracture potential by shear stress because parallel fibers are not
      mechanically resistant to support oblique occlusal loads. Factors such as the
      presence of remaining coronal tooth structure and occlusal stability assist in
      the biomechanical equilibrium of stresses that act upon anterior teeth.

PMID- 27689842
TI  - Aging and well-being in Goa, India: a qualitative study.
AB  - OBJECTIVES: The population of India is aging rapidly. This demographic shift
      brings with it a host of challenges to the health and well-being of older adults,
      including the increased prevalence of non-communicable diseases, among them
      depressive disorders. In this paper, we report on qualitative research intended
      to inform the development of a locally acceptable and appropriate intervention to
      improve the well-being of older adults in Goa, India and, specifically, to
      prevent late-life depression. METHOD: Semi-structured interviews with 20
      individuals, aged 60 years and older, attending two primary care clinics in Goa,
      India. Transcripts were reviewed to identify emerging themes, a coding scheme was
      developed and thematic analyses were conducted. RESULTS: Analyses of the
      interview transcripts revealed the following key themes: (1) notions of old age
      tended to be negative and there were widespread fears of becoming widowed or
      incapacitated; (2) the most frequently reported health conditions were joint
      pain, diabetes and heart disease; (3) emotional distress was described using the
      terms 'tension', 'stress', 'worry' and 'thinking'; (4) family issues often
      involved financial matters, difficult relationships with daughters-in-law and
      conflicted feelings about living with the family or independently; (5) other than
      a pension scheme, participants did not know of community resources available to
      older adults. CONCLUSIONS: Our findings are in general agreement with those of
      previous research, and with our experiences of working with older adults in
      Pittsburgh and the Netherlands. This research will inform the development of an
      intervention to prevent depression in older adults in Goa.

PMID- 27689843
TI  - Trading direct for indirect defense? Phytochrome B inactivation in tomato
      attenuates direct anti-herbivore defenses whilst enhancing volatile-mediated
      attraction of predators.
AB  - Under conditions of competition for light, which lead to the inactivation of the
      photoreceptor phytochrome B (phyB), the growth of shade-intolerant plants is
      promoted and the accumulation of direct anti-herbivore defenses is down
      regulated. Little is known about the effects of phyB on emissions of volatile
      organic compounds (VOCs), which play a major role as informational cues in
      indirect defense. We investigated the effects of phyB on direct and indirect
      defenses in tomato (Solanum lycopersicum) using two complementary approaches to
      inactivate phyB: illumination with a low red to far-red ratio, simulating
      competition, and mutation of the two PHYB genes present in the tomato genome.
      Inactivation of phyB resulted in low levels of constitutive defenses and down
      regulation of direct defenses induced by methyl jasmonate (MeJA). Interestingly,
      phyB inactivation also had large effects on the blends of VOCs induced by MeJA.
      Moreover, in two-choice bioassays using MeJA-induced plants, the predatory mirid
      bug Macrolophus pygmaeus preferred VOCs from plants in which phyB was inactivated
      over VOCs from control plants. These results suggest that, in addition to
      repressing direct defense, phyB inactivation has consequences for VOC-mediated
      tritrophic interactions in canopies, presumably attracting predators to less
      defended plants, where they are likely to find more abundant prey.

PMID- 27689844
TI  - Micro-CT assessment of dentinal micro-cracks after root canal filling procedures.
AB  - AIM: To evaluate the frequency of dentinal micro-cracks after root canal filling
      procedures with GuttaCore (GC), cold lateral compaction (CLC) and warm vertical
      compaction (WVC) techniques in mandibular molars using micro-computed tomographic
      analysis. METHODOLOGY: Thirty mesial roots of mandibular molars, with a type II
      Vertucci's canal configuration, were prepared to working length with a Reciproc
      R40 instrument and randomly assigned to one of the three experimental groups (n =
      10), according to the technique used for root filling: GC, CLC or WVC. The GC
      group was filled with a size 40 GC obturator, whilst CLC and WVC groups used
      conventional gutta-percha cones. AH Plus sealer was used in all groups. The
      specimens were scanned at an isotropic resolution of 14.25 MUm before and after
      root canal preparation and after root filling. Then, all pre- and postoperative
      cross-sectional images of the roots (n = 41 660) were screened to identify the
      presence of dentinal defects. RESULTS: Overall, 30.75% (n = 12 810) of the pre- +
      post-filling images displayed dentinal defects. In the GC, CLC and WVC groups,
      dentinal micro-cracks were observed in 18.68% (n = 2510), 15.99% (n = 2389) and
      11.34% (n = 1506) of the cross-sectional images, respectively. All micro-cracks
      identified in the post-filling scans were also observed in the corresponding post
      preparation images. CONCLUSION: Root fillings in all techniques did not induce
      the development of new dentinal micro-cracks.

PMID- 27689845
TI  - Outcome of neoadjuvant therapies for cancer of the oesophagus or gastro
      oesophageal junction based on a national data registry.
AB  - BACKGROUND: Randomized trials have shown that neoadjuvant treatment improves
      survival in the curative treatment of oesophageal and gastro-oesophageal junction
      cancer. Results from population-based observational studies are, however, sparse
      and ambiguous. METHODS: This prospective population-based cohort study included
      all patients who had oesophagectomy for cancer in Sweden, excluding clinical T1
      N0, recorded in the National Register for Oesophageal and Gastric Cancer, 2006
      2014. Patients were stratified into three groups: surgery alone, neoadjuvant
      chemotherapy and neoadjuvant chemoradiotherapy. RESULTS: Neoadjuvant treatment
      was given to 521 patients (51.1 per cent) and 499 (48.9 per cent) received
      surgery alone. Neoadjuvant chemotherapy increased the risk of postoperative
      surgical complications compared with surgery alone (adjusted odds ratio 2.01, 95
      per cent c.i. 1.24 to 3.25; P = 0.005). Postoperative mortality was significantly
      increased after neoadjuvant chemoradiotherapy compared with surgery alone (odds
      ratio 2.37, 1.06 to 5.29; P = 0.035). Survival improved in patients with squamous
      cell carcinoma after neoadjuvant chemotherapy, whereas after neoadjuvant
      chemoradiotherapy survival was significantly improved only in the subgroup with
      the highest performance status and without known co-morbidity. In adenocarcinoma
      there was a trend towards improved overall survival after neoadjuvant
      chemotherapy, but neoadjuvant chemoradiotherapy did not offer a survival benefit.
      Stratified analysis including only patients with adenocarcinoma in the highest
      performance category without known co-morbidity showed a strong trend towards
      improved survival after neoadjuvant chemotherapy compared with surgery alone
      (adjusted hazard ratio 0.47, 0.21 to 1.04; P = 0.061). CONCLUSION: For patients
      with squamous cell carcinoma of the oesophagus or gastro-oesophageal junction,
      neoadjuvant treatments seemed to increase long-term survival, but also the risk
      of postoperative morbidity and mortality, compared with surgery alone. Neither
      neoadjuvant treatment option seemed to improve survival significantly among
      patients with adenocarcinoma, compared with surgery alone.

PMID- 27689846
TI  - Enzymatic Ugi Reaction with Amines and Cyclic Imines.
AB  - The application of the Ugi reaction to the construction of new peptide scaffolds
      is an important goal of organic chemistry. To date, there are no examples of the
      Ugi reaction being performed with a cyclic imine and amine simultaneously. The
      application of 2-substituted cyclic imines in an enzymatic three-component Ugi
      type reaction provides an elegant and attractive synthesis of substituted
      pyrrolidine and piperidine derivatives in up to 60 % yield. Results on studies of
      the selection of an enzyme, amount of water, and solvent used in a novel three
      component Ugi reaction and the limitations thereof are reported herein. The
      presented methodology exploiting enzyme promiscuity in the multicomponent
      reaction fulfills the requirements associated with green chemistry. Several
      methods, such as isotope labeling and enzyme inhibition, were used to probe the
      possible mechanism of this complex synthesis. This research is the first example
      of an enzyme-catalyzed Ugi-type reaction with an imine, amine, and isocyanide.

PMID- 27689848
TI  - Tandem mass spectrometry of novel ether-linked phospholipid analogs of anionic
      pulmonary surfactant phospholipids.
AB  - RATIONALE: Structural analogs of the bioactive lipid 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphoglycerol were synthesized with a xylitol polar head group and
      both diacyl and diether radyl groups. Mass spectral characterization of xylitol
      phospholipids (PX) was carried out using collisional activation and high
      resolution mass measurements of positive molecular ion species and compared with
      the phosphatidylglycerol (PG) analogs. METHODS: PX were synthesized using a
      transphosphatidylation reaction catalyzed by phospholipase D and purified by high
      performance liquid chromatography (HPLC). Compounds were subjected to
      electrospray ionization and collision-induced dissociation (CID) was performed
      using a tandem quadrupole mass spectrometer to generate positive and negative
      molecular ions. Diether phospholipids were additionally analyzed by high
      resolution mass spectrometry as protonated and sodiated molecular species in
      positive ion mode. RESULTS: Ester-linked PX analogs behaved similarly to PG after
      collisional activation of [M - H]- . The product ions formed by CID of the
      diether PG and PX negative ions only revealed information about the head group
      with no information about the aliphatic chains. In contrast, CID of protonated
      and sodiated diether phospholipid positive ions revealed reactions corresponding
      to cleavage of the ether chain, likely occurring by charge-driven reaction
      mechanisms. CONCLUSIONS: Novel PX analogs with diacyl and diether radyl
      substituents of the glycerol backbone were characterized by tandem mass
      spectrometry. These unique diether phospholipid analogs enabled exploration of
      ether cleavage reactions of the positive molecular ion species resulting from
      collision-induced decomposition. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27689847
TI  - Facile Fabrication of Tumor Redox-Sensitive Nanoassemblies of Small-Molecule
      Oleate Prodrug as Potent Chemotherapeutic Nanomedicine.
AB  - The conjugate of paclitaxel (PTX) and docosahexaenoic acid has entered into
      clinical trials. However, the most recent clinical outcomes fell short of
      expectations, due to the extremely slow drug release from the hydrophobic
      conjugates. Herein, a novel prodrug-based nanoplatform self-assembled by the
      disulfide bond linked conjugates of PTX and oleic acid for rapid and differential
      release of PTX in tumor cells is reported. This redox-responsive prodrug
      nanosystem demonstrates multiple therapeutic advantages, including one-step
      facile fabrication, high drug-loading efficiency (56%, w/w), on-demand drug
      release responding to redox stimuli, as well as favorable cellular uptake and
      biodistribution. These advantages result in significantly enhanced antitumor
      efficacy in vivo, with the tumor almost completely disappearing in mice. Such a
      uniquely engineered prodrug-nanosystem has great potential to be used as potent
      chemotherapeutic nanomedicine in clinical cancer therapy.

PMID- 27689850
TI  - Silica-Supported Silver Nitrate as a Highly Active Dearomatizing Spirocyclization
      Catalyst: Synergistic Alkyne Activation by Silver Nanoparticles and Silica.
AB  - Silica-supported AgNO3 (AgNO3 -SiO2 ) catalyzes the dearomatizing
      spirocyclization of alkyne-tethered aromatics far more effectively than the
      analogous unsupported reagent; in many cases, reactions which fail using
      unsupported AgNO3 proceed effectively with AgNO3 -SiO2 . Mechanistic studies
      indicate that this is a consequence of silver nanoparticle formation on the
      silica surface combined with a synergistic effect caused by the silica support
      itself. The remarkable ease with which the reagent can be prepared and used is
      likely to be of much synthetic importance, in particular, by making nanoparticle
      catalysis more accessible to non-specialists.

PMID- 27689849
TI  - Improved human endometrial stem cells differentiation into functional hepatocyte
      like cells on a glycosaminoglycan/collagen-grafted polyethersulfone nanofibrous
      scaffold.
AB  - Liver tissue engineering (TE) is rapidly emerging as an effective technique which
      combines engineering and biological processes to compensate for the shortage of
      damaged or destroyed liver tissues. We examined the viability, differentiation,
      and integration of hepatocyte-like cells on an electrospun polyethersulfone (PES)
      scaffold, derived from human endometrial stem cells (hEnSCs). Natural polymers
      were separately grafted on plasma-treated PES nanofibers, that is, collagen,
      heparan sulfate (HS) and collagen-HS. Galactosilated PES (PES-Gal) nanofibrous
      were created. The engineering and cell growth parameters were considered and
      compared with each sample. The cellular studies revealed increased cell survival,
      attachment, and normal morphology on the bioactive natural polymer-grafted
      scaffolds after 30 days of hepatic differentiation. The chemical and molecular
      assays displayed hepatocyte differentiation. These cells were also functional,
      showing glycogen storage, alpha-fetoprotein, and albumin secretion. The HS
      nanoparticle-grafted PES nanofibers demonstrated a high rate of cell
      proliferation, differentiation, and integration. Based on the observations
      mentioned above, engineered tissue is a good option in the future, for the
      commercial production of three-dimensional liver tissues for clinical purposes.
      (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B:
      2516-2529, 2017.

PMID- 27689851
TI  - The Role of Excitons on Light Amplification in Lead Halide Perovskites.
AB  - The role of excitons on the amplifications of lead halide perovskites has been
      explored. Unlike the photoluminescence, the intensity of amplified spontaneous
      emission is partially suppressed at low temperature. The detailed analysis and
      experiments show that the inhibition is attributed to the existence of exciton
      and a quantitative model has been built to explain the experimental observations.

PMID- 27689852
TI  - Hyaluronan oligosaccharides stimulate matrix metalloproteinase and anabolic gene
      expression in vitro by intervertebral disc cells and annular repair in vivo.
AB  - The role of hyaluronan (HA) oligosaccharides in disc cell-mediated matrix
      metalloproteinase (MMP) and anabolic gene expression in vitro and annular repair
      in vivo were examined. Monolayer and alginate bead cultures of ovine
      intervertebral disc cells were stimulated with 10-12 mer hyaluronan
      oligosaccharides (HA-oligos). Annulus fibrosus (AF) monolayers were poorly
      responsive to the HA-oligos, proMMP-2 levels were marginally elevated and levels
      were MMP-9 unaffected. ProMMP-2 displayed a strong dose-dependent increase in the
      nucleus pulposus (NP) monolayers. In AF alginate bead cultures, proMMP-2 and
      active MMP-9 increased up to day 10, in NP cultures proMMP-2 was progressively
      converted to active MMP-2 over days 7-10 and active MMP-9 levels were elevated on
      day 10. A steady decline in MMP-2 and MMP-9 activity was evident over days 2-10
      in the non-stimulated NP cultures. Disc cell viabilities were >=92 +/- 5% in all
      cultures indicating that the HA-oligo was not cytotoxic. Reverse-transcription
      polymerase chain reaction demonstrated an upregulation in MMP1, MMP113 and
      ADAMTS1 and the anabolic matrix repair genes ACAN, COL1A1 and COL2A1 in the NP by
      HA-oligos, whereas AF MMP13, ADAMTS1, ADAMTS4 and ADAMTS5, ACAN and COL2A1 were
      down-regulated; this differential regulation is expected to promote clearance of
      granulation/scar tissue from AF defects and matrix replenishment. The AF defect
      sites contained enlarged annular lamellae in vivo in response to the HA oligos,
      which is consistent with an active repair response. Masson trichrome and
      PicroSirius red histology and immunolocalization of type I collagen supported
      active remodelling in the outer lesion zone by the HA-oligo treatment but not the
      inner lesion. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27689853
TI  - Communicating Conservation Status: How Different Statistical Assessment Criteria
      Affect Perceptions of Extinction Risk.
AB  - Although alternative forms of statistical and verbal information are routinely
      used to convey species' extinction risk to policymakers and the public, little is
      known about their effects on audience information processing and risk
      perceptions. To address this gap in literature, we report on an experiment that
      was designed to explore how perceptions of extinction risk differ as a function
      of five different assessment benchmarks (Criteria A-E) used by scientists to
      classify species within IUCN Red List risk levels (e.g., Critically Endangered,
      Vulnerable), as well as the role of key individual differences in these effects
      (e.g., rational and experiential thinking styles, environmental concern). Despite
      their normative equivalence within the IUCN classification system, results
      revealed divergent effects of specific assessment criteria: on average,
      describing extinction risk in terms of proportional population decline over time
      (Criterion A) and number of remaining individuals (Criterion D) evoked the
      highest level of perceived risk, whereas the single-event probability of a
      species becoming extinct (Criterion E) engendered the least perceived risk.
      Furthermore, participants scoring high in rationality (analytic thinking) were
      less prone to exhibit these biases compared to those low in rationality. Our
      findings suggest that despite their equivalence in the eyes of scientific
      experts, IUCN criteria are indeed capable of engendering different levels of risk
      perception among lay audiences, effects that carry direct and important
      implications for those tasked with communicating about conservation status to
      diverse publics.

PMID- 27689854
TI  - Understanding PPAR-delta affinity and selectivity using hologram quantitative
      structure-activity modeling, molecular docking and GRID calculations.
AB  - AIM: Type 2 diabetes mellitus and metabolic syndrome are two diseases related to
      disorders of lipid and carbohydrate metabolism and insulin resistance. Peroxisome
      proliferator-activated receptors (PPARs) are a class of nuclear receptors that
      control the metabolism of lipids/carbohydrates and are considered targets for
      both diseases. PPAR affinity and selectivity are critical points to design drug
      candidates with appropriated pharmacodynamic/kinetic profiles. MATERIALS &
      METHODS: Hologram quantitative structure-activity relationships studies were
      conducted, as well molecular docking and molecular interaction field
      calculations, in order to explain affinity and selectivity of selected compounds.
      RESULTS: The constructed hologram quantitative structure-activity relationship
      models are robust and predictive (values of q2 and r2test above 0.70).
      CONCLUSION: The quantitative structure-activity relationship models and
      docking/GRID analyses indicated that carboxyl group of indole-sulfonamide
      derivatives could interact at helix-3 region, being considered important point of
      PPAR-delta selectivity.

PMID- 27689855
TI  - ?

PMID- 27689856
TI  - Providing Palliative Care, and Beyond....

PMID- 27689857
TI  - Application of flow cytometry for monitoring the production of poly(3
      hydroxybutyrate) by Halomonas boliviensis.
AB  - In this study, a flow cytometry (FC) protocol was implemented to measure poly(3
      hydroxybutyrate) (PHB) content in a halophilic bacterium, to have a faster and
      easier control of the process. The halophilic bacterium Halomonas boliviensis was
      stained with BODIPY 493/503 and analyzed using FC. Bacterial polymer accumulation
      induced by two different nutrient limitations during the operation of a 2 L
      bioreactor was studied using traditional gas chromatography (GC) analysis and FC.
      The application of this rapid and straightforward method is useful to obtain
      complex and precise information about PHB accumulation that could be used for the
      monitoring, control and optimization of the production of PHB. A clear
      correlation between the PHB concentration determined by GC and the fluorescence
      signal obtained from stained bacteria by using FC was observed. Additionally, the
      heterogeneity of bacterial population as a function of PHB content was measured.
      (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:276-284,
      2017.

PMID- 27689858
TI  - Long-term effect of chemotherapy-intensity-modulated radiation therapy (chemo
      IMRT) on dentofacial development in head and neck rhabdomyosarcoma patients.
AB  - Dentofacial developmental abnormalities have been reported in head and neck
      rhabdomyosarcoma (HNRMS) patients treated with conventional radiotherapy
      technique and chemotherapy. This current study investigates dentofacial long-term
      effects among HNRMS survivors managed with intensity-modulated radiotherapy
      (IMRT) and chemotherapy. In general, IMRT is a more effective 3D-conformal
      radiotherapy technique, which delivers high doses of radiation to the tumor
      target while minimizing doses received by the surrounding normal tissues. The
      medical records and radiographs of thirteen patients were reviewed to identify
      the following: 1. Facial asymmetry and jaw hypoplasia. 2. Effects on the dental
      tissue causing tooth agenesis/hypodontia, root agenesis/stunting/malformation,
      and/or enamel hypoplasia. 3. Trismus, hyposalivation/xerostomia. Seven patients
      presented with facial asymmetry and jaw hypoplasia, 9 patients presented with
      effects on the dental tissue [root agenesis/stunting/malformation (9), tooth
      agenesis/hypodontia (7) and enamel hypoplasia (3)] and 7 patients developed
      trismus and /or xerostomia. All patients with facial asymmetry and jaw hypoplasia
      also developed dental abnormalities. Patients with dentofacial developmental
      abnormalities were <=7 years of age at treatment. Our study shows that
      dentofacial developmental abnormalities are still a burden in the era of IMRT and
      as prognosis of childhood malignancy improves and more patients survive, these
      late dentofacial sequelae among childhood cancer survivors will become more
      common. Dental oncologists should be integral members in the management of
      children with head and neck cancers.

PMID- 27689859
TI  - Effect of uric acid-lowering therapy on blood pressure: systematic review and
      meta-analysis.
AB  - BACKGROUND: The purpose of this meta-analysis was to determine if uric acid
      lowering therapy is associated with a decrease in blood pressure (BP) and serum
      creatinine levels. MATERIALS AND METHODS: Medline, Cochrane, EMBASE, and Google
      Scholar databases were searched until 29 June 2016, with keywords: uric-acid
      lowering therapy, allopurinol, febuxostat, uricosuric, and BP. Only randomized
      controlled trials were included. The primary outcomes were reduction in systolic
      BP (SBP) and diastolic BP (DBP), and secondary was reduction in serum creatinine
      level. RESULTS: Patients treated with allopurinol had greater reduction in SBP
      (standardized difference in means [SDM] = 0.321, 95% confidence interval [CI]:
      0.145-0.497, p < 0.001), DBP (SDM = 0.260, 95% CI: 0.102 to 0.417, p = 0.001),
      and creatinine level (SDM = 0.312, 95% CI: 0.008 to 0.615, p = 0.044) than
      control patients. Subgroup analysis showed that allopurinol significantly
      decreased SBP whether or not antihypertensive drugs were being administered; a
      decrease in DBP was only seen in patients receiving antihypertensive drugs. Low
      dose allopurinol (<=300 mg/day) was more effective at reducing SBP than high-dose
      (>300 mg/day) in patients receiving antihypertensive drugs. CONCLUSIONS: These
      results support that allopurinol decreases BP and creatinine levels in patients
      with hyperuricemia. KEY MESSAGES Allopurinol decreases SBP and DPB, and
      creatinine levels in patients with hyperuricemia. Allopurinol resulted in a
      significant decrease in SBP in patients with or without treatment of
      antihypertensive drugs. A dose of allopurinol of <=300 mg per day might be more
      effective than a higher dose.

PMID- 27689860
TI  - Hearing voices, dissociation, and the self: A functional-analytic perspective.
AB  - In the current article, we review existing models of the etiology of voice
      hearing. We summarize the argument and evidence that voice hearing is primarily a
      dissociative process involving critical aspects of self. We propose a
      complementary perspective on these phenomena that is based on a modern behavioral
      account of complex behavior known as relational frame theory. This type of
      approach to voice hearing concerns itself with the functions served for the
      individual by this voice hearing; the necessary history, such as trauma, that
      establishes these functions; and the relevant dissociative processes involving
      self and others. In short, we propose a trauma-dissociation developmental
      trajectory in which trauma impacts negatively on the development of self through
      the process of dissociation. Using the relational frame theory concept of
      relations of perspective taking, our dissociation model purports that trauma
      gives rise to more coordination than distinction relations between self and
      others, thus weakening an individual's sense of a distinct self. Voice hearing
      experiences, therefore, reflect an individual's perceptions of self and others
      and may indicate impairments in the natural psychological boundaries between
      these critical related concepts. One clinical implication suggested by this model
      is that therapeutic intervention should understand the behaviors associated with
      a sense of self that is fragile and threatened by others. Relations with self and
      others should be a key focus of therapy as well as interventions designed to
      enhance a coherent distinct sense of self.

PMID- 27689861
TI  - Pillbox use, satisfaction, and effectiveness among persons with chronic health
      conditions.
AB  - The purpose of this study was to understand how persons with chronic health
      conditions use pillboxes, their satisfaction with current devices, and the impact
      of pillbox use on medication adherence. We used convergent parallel mixed methods
      approach to explore the experiences of 13 regular, 3 occasional, and 5 non
      pillbox users. Medication consumers completed the Quebec User Evaluation of
      Satisfaction with Assistive Technology (QUEST 2.0), an interview about their
      medication routines, and a medication adherence diary to describe their
      experiences with their pillboxes. Results demonstrated most participants use
      pillboxes to help manage their medications, and pillbox users tended to have
      better medication adherence than nonusers. Participants used a variety of
      pillboxes differing in size, shape, and color. Users reported selecting pillboxes
      based on their needs in addition to the demands of their habits and medication
      regimens. Users were generally satisfied with their pillboxes with an average
      QUEST score of 4.33. However, participants also identified areas for an improved
      design of pillboxes. Pillboxes can be an effective strategy to improve medication
      adherence. Improvements in device prescription, training, research, and design
      are needed to understand the mechanisms and size of effects of this intervention.

PMID- 27689863
TI  - Use of a Modified Canadian Occupational Performance Measure for Assistive
      Technology Outcomes in Postsecondary Education.
AB  - The Canadian Occupational Performance Measure (COPM) has been used to assess the
      effectiveness of assistive technology (AT). We explored whether a modified COPM
      was sensitive to change in perceived performance and satisfaction, and whether
      frequency of AT use resulted in greater change in the domains measured (reading,
      writing, note-taking, test-taking, and study skills). Significant interactions
      were found between time and use frequency with greater change in perceived
      performance in the daily-use group in several domains. In addition, the intra
      class correlation showed moderate to strong equivalent forms reliability between
      two assessment formats. Based on these preliminary results, the ATRC-mCOPM was
      found to be a sensitive measure of perceived performance and satisfaction
      utilizing AT services in a postsecondary education setting.

PMID- 27689864
TI  - Thrombolysis based on magnetically-controlled surface-functionalized Fe3O4
      nanoparticle.
AB  - In this study, the control of magnetic fields to manipulate surface
      functionalized Fe3O4 nanoparticles by urokinase coating is investigated for
      thrombolysis in a microfluidic channel. The urokinase-coated Fe3O4 nanoparticles
      are characterized using particle size distribution, zeta potential measurement
      and spectroscopic data. Thrombolytic ratio tests reveal that the efficiency for
      thrombus cleaning is significantly improved when using magnetically-controlled
      urokinase-coated Fe3O4 nanoparticles than pure urokinase solution. The average
      increase in the rate of thrombolysis with the use of urokinase-coated Fe3O4
      nanoparticles is about 50%. In vitro thrombolysis test in a microfluidic channel
      using the coated nanoparticles shows nearly complete removal of thrombus, a
      result that can be attributed to the clot busting effect of the urokinase as it
      inhibits the possible formation of blood bolus during the magnetically-activated
      microablation process. The experiment further demonstrates that a thrombus mass
      of 10.32 mg in the microchannel is fully removed in about 180 s.

PMID- 27689865
TI  - Cadherin-11 modulates cell morphology and collagen synthesis in periodontal
      ligament cells under mechanical stress.
AB  - OBJECTIVE: To examine the role of cadherin-11, an integral membrane adhesion
      molecule, in periodontal ligament cells (PDLCs) under mechanical stimulation.
      MATERIALS AND METHODS: Human PDLCs were cultured and subjected to mechanical
      stress. Cadherin-11 expression and cell morphology of PDLCs were investigated via
      immunofluorescence staining. The mRNA and protein expressions of cadherin-11 and
      type I collagen (Col-I) of PDLCs were evaluated by quantitative real-time
      polymerase chain reaction and Western blot, respectively. Small interfering RNA
      was used to knock down cadherin-11 expression in PDLCs. The collagen matrix of
      PDLCs was examined using toluidine blue staining. RESULTS: Cadherin-11 was
      expressed in PDLCs. Mechanical stress suppressed cadherin-11 expression in PDLCs
      with prolonged force treatment time and increased force intensity, accompanied by
      suppressed beta-catenin expression. Simultaneously, mechanical stress altered
      cell morphology and repressed Col-I expression in a time- and dose-dependent
      manner in PDLCs. Moreover, knockdown of cadherin-11 with suppressed beta-catenin
      expression resulted in altered PDLC morphology and repressed collagen expression,
      which were consistent with the changes observed under mechanical stress.
      CONCLUSIONS: Results of this study suggest that cadherin-11 is expressed in PDLCs
      and modulates PDLC morphology and collagen synthesis in response to mechanical
      stress, which may play an important role in the homeostasis and remodeling of the
      PDL under mechanical stimulation.

PMID- 27689867
TI  - Use of Carbon Nanotubes as a Solid Support To Establish Quantitative
      (Centrifugation) and Qualitative (Filtration) Immunoassays To Detect Gentamicin
      Contamination in Commercial Milk.
AB  - Current methods to detect gentamicin (GEN), a broad-spectrum antibiotic that
      causes ototoxicity and nephrotoxicity when present in excess, have several
      limitations. Hence, we have developed two methods using multi-walled carbon
      nanotubes (MWCNTs) as a solid support to detect GEN. Hybridoma cells (2D12)
      producing high-sensitivity antibodies against GEN were established. The goat anti
      mouse antibody was immobilized on MWCNTs directly or using bifunctional
      polyethylene glycol as a linker. On the basis of the physical characteristics of
      MWCNTs, a quantitative method involving centrifugation separation and a
      qualitative method involving filtration separation were established. Various
      experimental parameters were optimized for GEN detection, and recovery tests were
      performed. For the quantitative method, the limit of detection (LOD) was 0.048
      ng/mL, whereas for the qualitative method, a LOD of 0.1 ng/mL was observed by the
      naked eye. The proposed immunoassays were applied to commercial milk samples.
      Thus, these methods show potential application for the detection of GEN.

PMID- 27689868
TI  - Oral health educational interventions for nursing home staff and residents.
AB  - BACKGROUND: Associations between nursing home residents' oral health status and
      quality of life, respiratory tract infections, and nutritional status have been
      reported. Educational interventions for nurses or residents, or both, focusing on
      knowledge and skills related to oral health management may have the potential to
      improve residents' oral health. OBJECTIVES: To assess the effects of oral health
      educational interventions for nursing home staff or residents, or both, to
      maintain or improve the oral health of nursing home residents. SEARCH METHODS: We
      searched the Cochrane Oral Health Trials Register (to 18 January 2016), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library,
      2015, Issue 12), MEDLINE Ovid (1946 to 18 January 2016), Embase Ovid (1980 to 18
      January 2016), CINAHL EBSCO (1937 to 18 January 2016), and Web of Science
      Conference Proceedings (1990 to 18 January 2016). We searched ClinicalTrials.gov
      and the World Health Organization International Clinical Trials Registry Platform
      for ongoing trials to 18 January 2016. In addition, we searched reference lists
      of identified articles and contacted experts in the field. We placed no
      restrictions on language or date of publication when searching the electronic
      databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster
      RCTs comparing oral health educational programmes for nursing staff or residents,
      or both with usual care or any other oral healthcare intervention. DATA
      COLLECTION AND ANALYSIS: Two review authors independently screened articles
      retrieved from the searches for relevance, extracted data from included studies,
      assessed risk of bias for each included study, and evaluated the overall quality
      of the evidence. We retrieved data about the development and evaluation processes
      of complex interventions on the basis of the Criteria for Reporting the
      Development and Evaluation of Complex Interventions in healthcare: revised
      guideline (CReDECI 2). We contacted authors of relevant studies for additional
      information. MAIN RESULTS: We included nine RCTs involving 3253 nursing home
      residents in this review; seven of these trials used cluster randomisation. The
      mean resident age ranged from 78 to 86 years across studies, and most
      participants were women (more than 66% in all studies). The proportion of
      residents with dental protheses ranged from 62% to 87%, and the proportion of
      edentulous residents ranged from 32% to 90% across studies.Eight studies compared
      educational interventions with information and practical components versus
      (optimised) usual care, while the ninth study compared educational interventions
      with information only versus usual care. All interventions included educational
      sessions on oral health for nursing staff (five trials) or for both staff and
      residents (four trials), and used more than one active component. Follow-up of
      included studies ranged from three months to five years.No study showed overall
      low risk of bias. Four studies had a high risk of bias, and the other five
      studies were at unclear risk of bias.None of the trials assessed our predefined
      primary outcomes 'oral health' and 'oral health-related quality of life'. All
      trials assessed our third primary outcome, 'dental or denture plaque'. Meta
      analyses showed no evidence of a difference between interventions and usual care
      for dental plaque (mean difference -0.04, 95% confidence interval (CI) -0.26 to
      0.17; six trials; 437 participants; low quality evidence) or denture plaque
      (standardised mean difference -0.60, 95% CI -1.25 to 0.05; five trials; 816
      participants; low quality evidence). None of the studies assessed adverse events
      of the intervention. AUTHORS' CONCLUSIONS: We found insufficient evidence to draw
      robust conclusions about the effects of oral health educational interventions for
      nursing home staff and residents. We did not find evidence of meaningful effects
      of educational interventions on any measure of residents' oral health; however,
      the quality of the available evidence is low. More adequately powered and high
      quality studies using relevant outcome measures are needed.

PMID- 27689866
TI  - Chemical Proteomic Profiling of Human Methyltransferases.
AB  - Methylation is a fundamental mechanism used in Nature to modify the structure and
      function of biomolecules, including proteins, DNA, RNA, and metabolites. Methyl
      groups are predominantly installed into biomolecules by a large and diverse class
      of S-adenosyl methionine (SAM)-dependent methyltransferases (MTs), of which there
      are ~200 known or putative members in the human proteome. Deregulated MT activity
      contributes to numerous diseases, including cancer, and several MT inhibitors are
      in clinical development. Nonetheless, a large fraction of the human MT family
      remains poorly characterized, underscoring the need for new technologies to
      characterize MTs and their inhibitors in native biological systems. Here, we
      describe a suite of S-adenosyl homocysteine (SAH) photoreactive probes and their
      application in chemical proteomic experiments to profile and enrich a large
      number of MTs (>50) from human cancer cell lysates with remarkable specificity
      over other classes of proteins. We further demonstrate that the SAH probes can
      enrich MT-associated proteins and be used to screen for and assess the
      selectivity of MT inhibitors, leading to the discovery of a covalent inhibitor of
      nicotinamide N-methyltransferase (NNMT), an enzyme implicated in cancer and
      metabolic disorders. The chemical proteomics probes and methods for their
      utilization reported herein should prove of value for the functional
      characterization of MTs, MT complexes, and MT inhibitors in mammalian biology and
      disease.

PMID- 27689869
TI  - Rapid, Surfactant-Free, and Quantitative Functionalization of Gold Nanoparticles
      with Thiolated DNA under Physiological pH and Its Application in Molecular Beacon
      Based Biosensor.
AB  - The controlled attachment of thiolated DNA to gold nanoparticles (AuNPs) dictates
      many applications. This is typically achieved by either "aging-salting" processes
      or low-pH method, where either Na+ or H+ is used to minimize charge repulsion and
      facilitate attachment of thiolated DNA onto AuNPs. However, the "aging-salting"
      process takes a long time, and is prone to aggregation when used with larger
      AuNPs. Surfactants are needed to precoat and thereby enhance the stability of
      AuNPs. The low-pH method can disrupt the structural integrity of DNAs. We report
      here an oligoethylene glycol (OEG) spacer-assisted method that enables
      quantitative and instantaneous attachment at physiological pH without the need
      for surfactants. The method is based on our finding that an uncharged OEG spacer
      as short as six EG units can effectively shield against repulsion between AuNPs
      and DNAs, substantially enhancing both the adsorption kinetics and thermodynamics
      of thiolated DNAs. We applied this to thiolated DNAs of various lengths and thiol
      modification positions and to large AuNPs. Importantly, our method also allows
      for the direct immobilization of thiolated molecular beacons (MB), and avoids
      particle aggregation due to intermolecular hydrogen bonding. The prepared MB
      AuNPs were successfully used for the fluorescent detection of target DNA at
      nanomolar concentrations. The OEG spacer appears to offer a highly effective
      parameter for tuning DNA adsorption kinetics and thermodynamics besides pH and
      salt, providing a novel means for highly controllable and versatile
      functionalization of AuNPs.

PMID- 27689870
TI  - Novel Bivalent 99mTc-Complex with N-Methyl-Substituted Hydroxamamide as Probe for
      Imaging of Cerebral Amyloid Angiopathy.
AB  - Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid
      aggregates in the walls of the cerebral vasculature. Recently, the development of
      molecular imaging probes targeting CAA has been attracting much attention. We
      previously reported the 99mTc-hydroxamamide (99mTc-Ham) complex with a bivalent
      benzothiazole scaffold as a binding moiety for amyloid aggregates ([99mTc]BT2)
      and its utility for CAA-specific imaging. However, the simultaneous generation of
      two radiolabeled complexes derived from the geometric isomers was observed in the
      99mTc-labeling reaction. It was recently reported that the complexation reaction
      of 99Tc with N-methyl-substituted Ham provided a single 99Tc-Ham complex
      consisting of two N-methylated Ham ligands with marked stability. In this
      article, we designed and synthesized a novel N-methylated bivalent 99mTc-Ham
      complex ([99mTc]MBT2) and evaluated its utility for CAA-specific imaging. N
      Methyl substitution of [99mTc]BT2 prevented the generation of its isomer in the
      99mTc-labeling reaction. Enhanced in vitro stability of [99mTc]MBT2 as compared
      with [99mTc]BT2 was observed. [99mTc]MBT2 showed very low brain uptake, which is
      favorable for CAA-specific imaging. An in vitro inhibition assay using beta
      amyloid aggregates and in vitro autoradiographic examination of brain sections
      from a Tg2576 mouse and a CAA patient showed a decline in the binding affinity
      for amyloid aggregates due to N-methylation of the 99mTc-Ham complex. These
      results suggest that the scaffold of the 99mTc-Ham complex may play important
      roles in the in vitro stability and the binding affinity for amyloid aggregates.

PMID- 27689871
TI  - Functional disparities among BCL-2 members in tonsillar and leukemic B-cell
      subsets assessed by BH3-mimetic profiling.
AB  - For successful treatment of malignant B-cells it is crucial to understand
      intrinsic survival requirements in relation to their normal progenitors. Long
      lived humoral immunity as well as most B-cell malignancies, originate in the
      germinal center (GC). Murine GC B-cells depend on pro-survival protein MCL-1, but
      not BCL-XL. In contrast, naive and memory B-cells depend on BCL-2, but not BCL-XL
      or MCL-1. For human B-cell subsets, the functional relationships among BCL-2
      members are unclear, and also if and how they shift after malignant
      transformation. We here dissect these aspects in human tonsil and primary
      leukemia (CLL) cells by single and combined treatment with novel, highly specific
      BH3-mimetics. We found that MCL-1 expression in GC B-cells is regulated post
      translationally and its importance is highlighted by preferential binding to pro
      apoptotic BIM. In contrast, BCL-XL is transcriptionally induced and binds solely
      to weak sensitizer BIK, potentially explaining why BCL-XL is not required for GC
      B-cell survival. Using novel BH3-mimetics, we found that naive and memory B-cells
      depend on BCL-2, GC cells predominantly on MCL-1, whereas plasma cells need both
      BCL-XL and MCL-1 for survival. CLL cells switch from highly sensitive for BCL-2
      inhibition to resistant after CD40-stimulation. However, combined inhibition of
      BCL-2, plus BCL-XL or MCL-1 effectively kills these cells, thus exposing a
      weakness that may be therapeutically useful. These general principles offer
      important clues for designing treatment strategies for B-cell malignancies.

PMID- 27689873
TI  - Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export.
AB  - AMPK is a central energy sensor linking extracellular milieu fluctuations with
      the autophagic machinery. In the current study we uncover that Poly(ADP
      ribosyl)ation (PARylation), a post-translational modification (PTM) of proteins,
      accounts for the spatial and temporal regulation of autophagy by modulating AMPK
      subcellular localisation and activation. More particularly, we show that the
      minority AMPK pool needs to be exported to the cytosol in a PARylation-dependent
      manner for optimal induction of autophagy, including ULK1 phosphorylation and
      mTORC1 inactivation. PARP-1 forms a molecular complex with AMPK in the nucleus in
      non-starved cells. In response to nutrient deprivation, PARP-1 catalysed
      PARylation, induced the dissociation of the PARP-1/AMPK complex and the export of
      free PARylated nuclear AMPK to the cytoplasm to activate autophagy. PARP
      inhibition, its silencing or the expression of PARylation-deficient AMPK mutants
      prevented not only the AMPK nuclear-cytosolic export but also affected the
      activation of the cytosolic AMPK pool and autophagosome formation. These results
      demonstrate that PARylation of AMPK is a key early signal to efficiently convey
      extracellular nutrient perturbations with downstream events needed for the cell
      to optimize autophagic commitment before autophagosome formation.

PMID- 27689872
TI  - Alternative splicing and cell survival: from tissue homeostasis to disease.
AB  - Most human genes encode multiple mRNA variants and protein products through
      alternative splicing of exons and introns during pre-mRNA processing. In this
      way, alternative splicing amplifies enormously the coding potential of the human
      genome and represents a powerful evolutionary resource. Nonetheless, the
      plasticity of its regulation is prone to errors and defective splicing underlies
      a large number of inherited and sporadic diseases, including cancer. One key
      cellular process affected by alternative splicing is the programmed cell death or
      apoptosis. Many apoptotic genes encode for splice variants having opposite roles
      in cell survival. This regulation modulates cell and tissue homeostasis and is
      implicated in both developmental and pathological processes. Furthermore, recent
      evidence has also unveiled splicing-mediated regulation of genes involved in
      autophagy, another essential process for tissue homeostasis. In this review, we
      highlight some of the best-known examples of alternative splicing events involved
      in cell survival. Emphasis is given to the role of this regulation in human
      cancer and in the response to chemotherapy, providing examples of how alternative
      splicing of apoptotic genes can be exploited therapeutically.

PMID- 27689874
TI  - Hepatocyte growth factor renders BRAF mutant human melanoma cell lines resistant
      to PLX4032 by downregulating the pro-apoptotic BH3-only proteins PUMA and BIM.
AB  - A large proportion of melanomas harbour the activating BRAFV600E mutation that
      renders these cells dependent on MAPK signalling for their survival. Although the
      highly specific and clinically approved BRAFV600E kinase inhibitor, PLX4032,
      induces apoptosis of melanoma cells bearing this mutation, the underlying
      molecular mechanisms are not fully understood. Here, we reveal that PLX4032
      induced apoptosis depends on the induction of the pro-apoptotic BH3-only protein
      PUMA with a minor contribution of its relative BIM. Apoptosis could be
      significantly augmented when PLX4032 was combined with an inhibitor of the pro
      survival protein BCL-XL, whereas neutralization of the pro-survival family member
      BCL-2 caused no additional cell death. Although the initial response to PLX4032
      in melanoma patients is very potent, resistance to the drug eventually develops
      and relapse occurs. Several factors can cause melanoma cells to develop
      resistance to PLX4032; one of them is the activation of the receptor tyrosine
      kinase cMET on melanoma cells by its ligand, hepatocyte growth factor (HGF),
      provided by the tumour microenvironment or the cancer cells themselves. We found
      that HGF mediates resistance of cMET-expressing BRAF mutant melanoma cells to
      PLX4032-induced apoptosis through downregulation of PUMA and BIM rather than by
      increasing the expression of pro-survival BCL-2-like proteins. These results
      suggest that resistance to PLX4032 may be overcome by specifically increasing the
      levels of PUMA and BIM in melanoma cells through alternative signalling cascades
      or by blocking pro-survival BCL-2 family members with suitable BH3 mimetic
      compounds.

PMID- 27689875
TI  - The role of 53BP1 protein in homology-directed DNA repair: things get a bit
      complicated.

PMID- 27689877
TI  - Lymph node stroma join the cancer support network.

PMID- 27689876
TI  - LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility
      in mouse.
AB  - Premature ovarian failure and female infertility are frequent side effects of
      anticancer therapies, owing to the extreme sensitivity of the ovarian reserve
      oocytes to the damaging effects of irradiation and chemotherapy on DNA. We report
      here a robust protective effect of luteinizing hormone (LH) on the primordial
      follicle pool of prepubertal ovaries against the cisplatin (Cs)-induced
      apoptosis. In vitro LH treatment of prepubertal ovarian fragments generated anti
      apoptotic signals by a subset of ovarian somatic cells expressing LH receptor
      (LHR) through cAMP/PKA and Akt pathways. Such signals, reducing the oocyte level
      of pro-apoptotic TAp63 protein and favoring the repair of the Cs-damaged DNA in
      the oocytes, prevented their apoptosis. Noteworthy, in vivo administration to
      prepubertal female mice of a single dose of LH together with Cs inhibited the
      depletion of the primordial follicle reserve caused by the drug and preserved
      their fertility in reproductive age, preventing significant alteration in the
      number of pregnancy and of delivered pups. In conclusion, these findings
      establish a novel ovoprotective role for LH and further support the very
      attracting prospective to use physiological 'fertoprotective' approaches for
      preventing premature infertility and risks linked to precocious menopause in
      young patients who survived cancer after chemotherapy.

PMID- 27689879
TI  - Mass Spectrometric and Functional Aspects of Drug-Protein Conjugation.
AB  - The covalent binding of drugs (metabolites) to proteins to form drug-protein
      adducts can have an adverse effect on the body. These adducts are thought to be
      responsible for idiosyncratic drug reactions including severe drug
      hypersensitivity reactions. Major advances in proteomics technology have allowed
      for the identification and quantification of target proteins for certain drugs.
      Human serum albumin (HSA) and Hb have been identified as accessible targets and
      potential biomarkers for drug-protein adducts formation, for numerous drugs
      (metabolites) including beta-lactam antibiotics, reactive drug metabolites such
      as quinone imines (acetaminophen) and acyl glucuronides (diclofenac), and
      covalent inhibitors (neratinib). For example, MS/MS analysis of plasma samples
      from patients taking flucloxacillin revealed that flucloxacillin and its 5
      hydroxymethyl metabolite formed covalent adducts with lysine residues on albumin
      via opening of the beta-lactam ring. Other proteins such as P450 and keratin are
      also potential targets for covalent binding. However, for most drugs, the
      properties of these target proteins including their location, their quantity, the
      timing of conjugate generation, and their biological function are not well
      understood. In this review, currently available proteomic technologies including
      MS/MS analysis to identify antigens, precise location of modifications, and the
      immunological consequence of hapten-protein complex are illustrated. Moving
      forward, identification of the nature of the antigenic determinants that trigger
      immune responses to drug-protein adducts will increase our ability to predict
      idiosyncratic toxicity for a given compound.

PMID- 27689878
TI  - Deficiency of Parkinson's disease-related gene Fbxo7 is associated with impaired
      mitochondrial metabolism by PARP activation.
AB  - The Parkinson's disease (PD)-related protein F-box only protein 7 (Fbxo7) is the
      substrate-recognition component of the Skp1-Cullin-F-box protein E3 ubiquitin
      ligase complex. We have recently shown that PD-associated mutations in Fbxo7
      disrupt mitochondrial autophagy (mitophagy), suggesting a role for Fbxo7 in
      modulating mitochondrial homeostasis. Here we report that Fbxo7 deficiency is
      associated with reduced cellular NAD+ levels, which results in increased
      mitochondrial NADH redox index and impaired activity of complex I in the electron
      transport chain. Under these conditions of compromised respiration, mitochondrial
      membrane potential and ATP contents are reduced, and cytosolic reactive oxygen
      species (ROS) production is increased. ROS activates poly (ADP-ribose) polymerase
      (PARP) activity in Fbxo7-deficient cells. PARP inhibitor restores cellular NAD+
      content and redox index and ATP pool, suggesting that PARP overactivation is
      cause of decreased complex I-driven respiration. These findings bring new insight
      into the mechanism of Fbxo7 deficiency, emphasising the importance of
      mitochondrial dysfunction in PD.

PMID- 27689880
TI  - The Gastroprotective Effect of Vitex pubescens Leaf Extract against Ethanol
      Provoked Gastric Mucosal Damage in Sprague-Dawley Rats.
AB  - Vitex pubescens is a Malaysian therapeutic plant employed in traditional drug to
      remedy a variety of disorders. The purpose of this research is to assess the
      gastroprotective efficiency of V. pubescens leaves against ethanol-induced
      gastric hemorrhagic laceration in rats. Animals were randomly allocated into
      seven groups and pre-treated, separately, with 10% Tween 20 (normal and ulcer
      control groups), 20 mg/kg omeprazole (reference group), and 62.5, 125, 250, and
      500 mg/kg of V. pubescens extract (experimental groups). All animals were
      sacrificed after another hour. Histological evaluation of the ulcer control group
      revealed significant injury to the gastric mucosa with edema and leucocyte
      infiltration of the submucosal layer. PAS staining, showed remarkably intense
      magenta color, remarkable increase of HSP70 and decrease of Bax proteins in rats
      pre-treated with plant extracts compared to the ulcer control group. Gastric
      homogenates revealed a remarkable increase in endogenous antioxidant enzyme
      activities (CAT, SOD, GSH) and a decrease in the lipid peroxidation level (MDA)
      in animals pre-treated with V. pubescens extract compared with the ulcer control
      group. The gastroprotective activity of this plant might be related to increased
      antioxidant enzymes and decrease lipid peroxidation upsurge of HSP70 and reduced
      expression of Bax proteins.

PMID- 27689881
TI  - The Insulin-Like Proteins dILPs-2/5 Determine Diapause Inducibility in
      Drosophila.
AB  - Diapause is an actively induced dormancy that has evolved in Metazoa to resist
      environmental stresses. In temperate regions, many diapausing insects overwinter
      at low temperatures by blocking embryonic, larval or adult development. Despite
      its Afro-tropical origin, Drosophila melanogaster migrated to temperate regions
      of Asia and Europe where females overwinter as adults by arresting gonadal
      development (reproductive diapause) at temperatures <13 degrees C. Recent work in
      D. melanogaster has implicated the developmental hormones dILPs-2 and/or dILP3,
      and dILP5, homologues of vertebrate insulin/insulin-like growth factors (IGFs),
      in reproductive arrest. However, polymorphisms in timeless (tim) and couch potato
      (cpo) dramatically affect diapause inducibility and these dILP experiments could
      not exclude this common genetic variation contributing to the diapause phenotype.
      Here, we apply an extensive genetic dissection of the insulin signaling pathway
      which allows us to see both enhancements and reductions in egg development that
      are independent of tim and cpo variations. We show that a number of manipulations
      dramatically enhance diapause to ~100%. These include ablating, or reducing the
      excitability of the insulin-producing cells (IPCs) that express dILPs-2,3,5
      employing the dilp2,3,5-/- triple mutant, desensitizing insulin signaling using a
      chico mutation, or inhibiting dILP2 and 5 in the hemolymph by over-expressing
      Imaginal Morphogenesis Protein-Late 2 (Imp-L2). In addition, triple mutant
      dilp2,3,5-/- females maintain high levels of diapause even when temperatures are
      raised in adulthood to 19 degrees C. However at 22 degrees C, these females all
      show egg development revealing that the effects are conditional on temperature
      and not a general female sterility. In contrast, over-expression of dilps-2/5 or
      enhancing IPC excitability, led to levels of ovarian arrest that approached zero,
      underscoring dILPs-2 and 5 as key antagonists of diapause.

PMID- 27689883
TI  - Efficacy of Six-Week Extended-Dose Nevirapine Varies by Infant Birth Weight with
      Greatest Relative Efficacy in Low Birth Weight Infants.
AB  - Latest World Health Organization guidelines recommend weight-based nevirapine
      prophylaxis for all HIV-exposed infants in resource-limited settings, yet low
      birth weight (LBW) infants (< 2500 g) have been understudied. Using data from the
      NIH-funded India six-week extended-dose nevirapine (SWEN) study, a randomized
      clinical trial of SWEN versus single-dose nevirapine (SD) for prevention of
      breast-milk HIV-1 transmission, we examined the relative impact of SWEN among 737
      mother-infant pairs stratified by infant birth weight. Birth weight groups were
      defined as very LBW (VLBW) <= 2000 g, moderate LBW (MLBW) >2000 g and <= 2500 g,
      and normal birth weight (NBW) > 2500 g. Outcomes were HIV-1 infection, HIV-1
      infection or death by 12 months, and severe adverse events (SAEs). The Kaplan
      Meier method was used to estimate probability of efficacy outcomes in birth
      weight groups, and differential effects of SWEN by birth weight group were
      examined using Cox proportional hazards models adjusting for independent risk
      factors for HIV maternal-to-child transmission and significant covariates. Among
      50 VLBW, 249 MLBW, and 433 NBW infants, 50% were randomized to SWEN; median
      gestational age was 36, 38 and 38 weeks, respectively; and there was no
      difference in breastfeeding duration (p = 0.99). Compared to SD: SWEN-treated
      VLBW had lower estimates of HIV-1 infection (13% vs. 38%, p = 0.004) and HIV-1
      infection or death (13% vs. 41%, p = 0.002); SWEN-treated MLBW had lower
      estimated HIV-1 infection (13% vs. 17%, p = 0.042); and efficacy endpoints were
      similar by treatment arm in NBW. In multivariate analysis, SWEN was associated
      with reduced risk of HIV-1 infection or death by 83% (p = 0.03) in VLBW versus
      45% (p = 0.05) in MLBW. SAE frequency was similar by treatment arm in VLBW (68%
      vs. 76%, p = 0.53) and MLBW (37% vs. 36%, p = 0.93). SWEN may safely increase HIV
      free survival among HIV-exposed LBW infants with greatest protective advantage
      among infants <= 2000 g.

PMID- 27689882
TI  - Synthesis and Evaluation of Paclitaxel-Loaded Gold Nanoparticles for Tumor
      Targeted Drug Delivery.
AB  - The synthesis of a series of thiolated paclitaxel analogs is described as part of
      a novel nanomedicine program aimed at developing formulations of paclitaxel that
      will bind to gold nanoparticles for tumor targeted drug delivery. Preliminary
      evaluation of the new nanomedicine composed of 27 nm gold nanoparticles, tumor
      necrosis factor alpha (TNFalpha), thiolated polyethylene glycol (PEG-thiol), and
      one of several thiolated paclitaxel analogs is presented.

PMID- 27689884
TI  - Knockdown of the schizophrenia susceptibility gene TCF4 alters gene expression
      and proliferation of progenitor cells from the developing human neocortex.
AB  - BACKGROUND: Common variants in the TCF4 gene are among the most robustly
      supported genetic risk factors for schizophrenia. Rare TCF4 deletions and loss-of
      function point mutations cause Pitt-Hopkins syndrome, a developmental disorder
      associated with severe intellectual disability. METHODS: To explore molecular and
      cellular mechanisms by which TCF4 perturbation could interfere with human
      cortical development, we experimentally reduced the endogenous expression of TCF4
      in a neural progenitor cell line derived from the developing human cerebral
      cortex using RNA interference. Effects on genome-wide gene expression were
      assessed by microarray, followed by Gene Ontology and pathway analysis of
      differentially expressed genes. We tested for genetic association between the set
      of differentially expressed genes and schizophrenia using genome-wide association
      study data from the Psychiatric Genomics Consortium and competitive gene set
      analysis (MAGMA). Effects on cell proliferation were assessed using high content
      imaging. RESULTS: Genes that were differentially expressed following TCF4
      knockdown were highly enriched for involvement in the cell cycle. There was a
      nonsignificant trend for genetic association between the differentially expressed
      gene set and schizophrenia. Consistent with the gene expression data, TCF4
      knockdown was associated with reduced proliferation of cortical progenitor cells
      in vitro. LIMITATIONS: A detailed mechanistic explanation of how TCF4 knockdown
      alters human neural progenitor cell proliferation is not provided by this study.
      CONCLUSION: Our data indicate effects of TCF4 perturbation on human cortical
      progenitor cell proliferation, a process that could contribute to cognitive
      deficits in individuals with Pitt-Hopkins syndrome and risk for schizophrenia.

PMID- 27689885
TI  - Prion Aggregates Are Recruited to the Insoluble Protein Deposit (IPOD) via Myosin
      2-Based Vesicular Transport.
AB  - Aggregation of amyloidogenic proteins is associated with several
      neurodegenerative diseases. Sequestration of misfolded and aggregated proteins
      into specialized deposition sites may reduce their potentially detrimental
      properties. Yeast exhibits a distinct deposition site for amyloid aggregates
      termed "Insoluble PrOtein Deposit (IPOD)", but nothing is known about the
      mechanism of substrate recruitment to this site. The IPOD is located directly
      adjacent to the Phagophore Assembly Site (PAS) where the cell initiates autophagy
      and the Cytoplasm-to-Vacuole Targeting (CVT) pathway destined for delivery of
      precursor peptidases to the vacuole. Recruitment of CVT substrates to the PAS was
      proposed to occur via vesicular transport on Atg9 vesicles and requires an intact
      actin cytoskeleton and "SNAP (Soluble NSF Attachment Protein) Receptor Proteins
      (SNARE)" protein function. It is, however, unknown how this vesicular transport
      machinery is linked to the actin cytoskeleton. We demonstrate that recruitment of
      model amyloid PrD-GFP and the CVT substrate precursor-aminopeptidase 1 (preApe1)
      to the IPOD or PAS, respectively, is disturbed after genetic impairment of Myo2
      based actin cable transport and SNARE protein function. Rather than accumulating
      at the respective deposition sites, both substrates reversibly accumulated often
      together in the same punctate structures. Components of the CVT vesicular
      transport machinery including Atg8 and Atg9 as well as Myo2 partially co
      localized with the joint accumulations. Thus we propose a model where vesicles,
      loaded with preApe1 or PrD-GFP, are recruited to tropomyosin coated actin cables
      via the Myo2 motor protein for delivery to the PAS and IPOD, respectively. We
      discuss that deposition at the IPOD is not an integrated mandatory part of the
      degradation pathway for amyloid aggregates, but more likely stores excess
      aggregates until downstream degradation pathways have the capacity to turn them
      over after liberation by the Hsp104 disaggregation machinery.

PMID- 27689886
TI  - Variation in perfluoroalkyl acids in the American alligator (Alligator
      mississippiensis) at Merritt Island National Wildlife Refuge.
AB  - This study aimed to quantify concentrations of fifteen perfluoroalkyl acids
      (PFAAs) in the plasma of American alligators (Alligator mississippiensis)
      inhabiting wetlands surrounding the Kennedy Space Center (KSC) in Florida, USA
      located at Merritt Island National Wildlife Refuge (MINWR). Approximately 10 male
      and 10 female alligators (ntotal = 229) were sampled each month during 2008 and
      2009 to determine if seasonal or spatial trends existed with PFAA burden. PFOS
      represented the highest plasma burden (median 185 ng/g) and PFHxS the second
      highest (median 7.96 ng/g). While no significant seasonal trends were observed,
      unique spatial trends emerged. Many of the measured PFAAs co-varied strongly
      together and similar trends were observed for PFOS, PFDA, PFUnA, and PFDoA, as
      well as for PFOA, PFHxS, PFNA, PFTriA, and PFTA, suggesting more than one source
      of PFAAs at MINWR. Higher concentrations of PFOS and the PFAAs that co-varied
      with PFOS were collected from animals around sites that included the Shuttle
      Landing Facility (SLF) fire house and the Neil Armstrong Operations and Checkout
      (O&C) retention pond, while higher concentrations of PFOA and the PFAA that co
      varied with PFOA were sampled from animals near the gun range and the old fire
      training facility. Sex-based differences and snout-vent length (SVL) correlations
      with PFAA burden were also investigated.

PMID- 27689887
TI  - Facile green synthesis of functional nanoscale zero-valent iron and studies of
      its activity toward ultrasound-enhanced decolorization of cationic dyes.
AB  - For the first time, an integrated green technology by coupling functional
      nanoscale zero-valent iron (NZVI) with ultrasound (US) was innovatively developed
      for the enhanced decolorization of malachite green (MG) and methylene blue (MB).
      The functional NZVI (TP-Fe) was successfully fabricated via a facile, one-step
      and environmentally-benign approach by directly introducing high pure tea
      polyphenol (TP), where TP contenting abundant epicatechin was employed as
      reductant, dispersant and capping agent. Note that neither additional extraction
      procedure nor protection gas was needed during the entire synthesis process.
      Affecting factors (including US frequency, initial pH, dye concentration, and
      reaction temperature) were investigated. Results show that TP-Fe exhibited
      enhanced activity, antioxidizability and stability over the reaction course,
      which could be attributed to the functionalization of TP on NZVI and the
      invigorating effect of US (i.e., improving the mass transfer rate, breaking up
      the aggregates of TP-Fe nanoparticles, and maintaining the TP-Fe surface
      activity). The kinetics for MG and MB decolorization by the TP-Fe/US system could
      be well described by a two-parameter pseudo-first-order decay model, and the
      activation energies of MG and MB decolorization in this new system were
      determined to be 21 kJ mol-1 and 24 kJ mol-1, respectively. In addition,
      according to the identified reaction products, a possible mechanism associated
      with MG and MB decolorization with the TP-Fe/US system was proposed.

PMID- 27689888
TI  - Copper-catalyzed activation of molecular oxygen for oxidative destruction of
      acetaminophen: The mechanism and superoxide-mediated cycling of copper species.
AB  - In this study, the commercial zero-valent copper (ZVC) was investigated to
      activate the molecular oxygen (O2) for the degradation of acetaminophen (ACT). 50
      mg/L ACT could be completely decomposed within 4 h in the ZVC/air system at
      initial pH 3.0. The H2O2, hydroxyl radical (OH) and superoxide anion radical (O2
      ) were identified as the main reactive oxygen species (ROSs) generated in the
      above reaction; however, only OH caused the decomposition and mineralization of
      ACT in the copper-catalyzed O2 activation process. In addition, the in-situ
      generated Cu+ from ZVC dissolution not only activated O2 to produce H2O2, but
      also initiated the decomposition of H2O2 to generate OH. Meanwhile, the H2O2
      could also be partly decomposed into O2-, which served as a mediator for copper
      cycling by reduction of Cu2+ to Cu+ in the ZVC/air system. Therefore, OH could be
      continuously generated; and then ACT was effectively degraded. Additionally, the
      effect of solution pH and the dosage of ZVC were also investigated. As a result,
      this study indicated the key behavior of the O2- during Cu-catalyzed activation
      of O2, which further improved the understanding of O2 activation mechanism by
      zero-valent metals.

PMID- 27689889
TI  - Bioelectrochemical approaches for removal of sulfate, hydrocarbon and salinity
      from produced water.
AB  - Produced water (PW) is the largest liquid waste stream generated during the
      exploration and drilling process of both the conventional hydrocarbon based
      resources like crude oil and natural gas, as well as the new fossil resources
      like shale gas and coal bed methane. Resource management, efficient utilization
      of the water resources, and water purification protocols are the conventionally
      used treatment methods applied to either treat or utilize the generated PW. This
      review provides a comprehensive overview of these conventional PW treatment
      strategies with special emphasises on electrochemical treatment. Key
      considerations associated with these approaches for efficient treatment of PW are
      also discussed. After a thorough assessment of the salient features of these
      treatment platforms, we propose a new strategy of uniquely integrating
      bioelectrochemical processes with biological system for more effective PW
      treatment and management.

PMID- 27689890
TI  - Rattle-type magnetic mesoporous hollow carbon as a high-performance and reusable
      adsorbent for water treatment.
AB  - Rattle-type magnetic mesoporous hollow carbon (RMMHC) materials have shown great
      promise as adsorbents for water treatment. In this work, we report a surfactant
      free synthesis of RMMHC nanoparticles (NPs) using magnetite NPs as the core,
      tetrapropyl orthosilicate, resorcinol and formaldehyde to form the shell followed
      by carbonization and selective silica etching. The pore size, specific surface
      area and pore volume of RMMHC NPs can be tuned by varying the carbonization
      temperature (500, 700 and 900  degrees C). At the optimized temperature of 700 
      degrees C, the RMMHC NPs possess the highest specific surface area of 579 m2 g-1,
      the largest pore volume of 0.795 cm3 g-1, and the largest pore size of 7.6 nm
      among all three samples. The adsorption capacity of optimized RMMHC NPs towards
      di (2-ethylhexyl) phthalate (a model organic pollutant) reaches as high as 783.1
      mg g-1. Taking advantage of the magnetic property, the adsorbents retain more
      than 87% of their initial adsorption capacity over five times' reuse.

PMID- 27689891
TI  - Simultaneous Quantification of Antioxidant Compounds in Phellinus igniarius Using
      Ultra Performance Liquid Chromatography-Photodiode Array Detection-Electrospray
      Ionization Tandem Mass Spectrometry.
AB  - Natural antioxidants are widely used in the life sciences. Phellinus igniarius is
      a historically used natural antioxidant containing a variety of active compounds.
      Phenols, particularly Inoscavin A and Hypholomine B, are found in the high
      concentrations. Better quantitative methods are needed to perform quality control
      in order to support further research of this mushroom. An ultra-performance
      liquid chromatography method coupled to photodiode-array detection and an
      electrospray ionization tandem mass spectrometry method (UPLC-PAD-MS) was
      developed to simultaneously quantify Inoscavin A and Hypholomine B levels in the
      medicinal fungus Phellinus igniarius. The two compounds were quantified using
      UPLC-PAD and UPLC-MS. The methods were accurate (mean accuracy for spiked matrix
      ranged from 101.5% to 105.8%), sensitive (limit of detection ranged from 0.28 to
      1.14 mg L-1) and precise (the relative standard deviations ranged from 0.13 to
      2.8%). Inoscavin A and Hypholomine B were purified using high-speed counter
      current chromatography (HSCCC), structural evaluated to meet the request of
      standard substances. UPLC separation was performed on a reversed-phase C18 column
      using gradient elution with acetonitrile and 0.1% formic acid over 10 min. The
      developed method was successfully applied to determine Inoscavin A and
      Hypholomine B in twelve Phellinus igniarius samples of different origins and the
      results showed that it was suitable for the analysis of these active components
      in Phellinus igniarius samples.

PMID- 27689892
TI  - High Throughput Analysis of Integron Gene Cassettes in Wastewater Environments.
AB  - Integrons are extensively targeted as a proxy for anthropogenic impact in the
      environment. We developed a novel high-throughput amplicon sequencing pipeline
      that enables characterization of thousands of integron gene cassette-associated
      reads, and applied it to acquire a comprehensive overview of gene cassette
      composition in effluents from wastewater treatment facilities across Europe.
      Between 38 100 and 172 995 reads per-sample were generated and functionally
      characterized by screening against nr, SEED, ARDB and beta-lactamase databases.
      Over 75% of the reads were characterized as hypothetical, but thousands were
      associated with toxin-antitoxin systems, DNA repair, cell membrane function,
      detoxification and aminoglycoside and beta-lactam resistance. Among the reads
      characterized as beta-lactamases, the carbapenemase blaOXA was dominant in most
      of the effluents, except for Cyprus and Israel where blaGES was also abundant.
      Quantitative PCR assessment of blaOXA and blaGES genes in the European effluents
      revealed similar trends to those displayed in the integron amplicon sequencing
      pipeline described above, corroborating the robustness of this method and
      suggesting that these integron-associated genes may be excellent targets for
      source tracking of effluents in downstream environments. Further application of
      the above analyses revealed several order-of-magnitude reductions in effluent
      associated beta-lactamase genes in effluent-saturated soils, suggesting marginal
      persistence in the soil microbiome.

PMID- 27689893
TI  - Using the Novel Method of Nonthermal Plasma To Add Cl Active Sites on Activated
      Carbon for Removal of Mercury from Flue Gas.
AB  - A new method using nonthermal plasma to add Cl active sites on activated carbon
      was proposed to improve the efficiency of activated carbon (AC) for removal of
      mercury from flue gas. The experiments were conducted via a lab-scale dielectric
      barrier discharge nonthermal plasma system and a vertical adsorption reactor. The
      results showed that the nonthermal plasma treatment with a small amount of Cl2
      successfully added Cl active sites on AC and greatly increased the mercury
      removal efficiency of AC by chemisorption in a very short treatment time. The
      increase in Cl2 concentration for AC treatment promoted the efficiency of AC. The
      capacity of mercury adsorption positively correlated with the content of Cl2 for
      AC treatment, which depends on the number of Cl active sites on activated carbon.
      The treated AC maintained a high mercury removal efficiency within a temperature
      range of 30-210  degrees C. SO2 and H2O in flue gas inhibited the removal of
      mercury by AC, while HCl had a promotional effect. Scanning electron microscopy
      and X-ray photoelectron spectroscopy analysis indicated the chemisorption of
      mercury was attributed to the C-Cl groups generated on AC surfaces during Cl2
      nonthermal plasma treatment. The C-Cl groups as active sites had strong
      adsorption energy for mercury, which converted elemental mercury to HgCl2.

PMID- 27689894
TI  - Does the development of executive functioning in infants born preterm benefit
      from maternal directiveness?
AB  - OBJECTIVE: Problems in early development of executive functioning may underlie
      the vulnerability and individual variability of infants born preterm for
      behavioral and learning problems. Parenting behaviors may aggravate or temper
      this increased risk for dysfunction. This study assessed how maternal parenting
      behaviors predict individual differences in early development of executive
      functioning in infants born preterm, and whether this varies with infant
      temperament, i.e., self-regulation. METHODS: Participants were 76 infants born
      preterm (<=36weeks' gestation and <2500g birth weight) and their mothers.
      Maternal sensitive responsiveness and directiveness were observed during a mother
      infant interaction situation at 7, 10 and 14months corrected age. At the same
      ages, executive functioning was measured using the A-not-B task. An infant self
      regulation questionnaire (IBQ-R) was completed by mothers at 7months. RESULTS:
      After controlling for perinatal risk factors, Multivariate Latent Growth Modeling
      showed that consistently higher levels of maternal directiveness predicted a
      stronger increase in A-not-B performance, which did not vary with infant self
      regulation. No relationship between maternal sensitive responsiveness and
      development in A-not-B performance in infants born preterm was found.
      CONCLUSIONS: These results suggest that preterm infants' early executive
      functioning development in the first year of life may benefit from a more and
      consistent directive approach by their mothers. These findings have important
      implications for early intervention programs aimed at facilitating preterm
      infants' development.

PMID- 27689895
TI  - Children's representations of another person's spatial perspective: Different
      strategies for different viewpoints?
AB  - The current study investigated development and strategy use of spatial
      perspective taking (i.e., the ability to represent how an object or array of
      objects looks from other viewpoints) in children between 8 and 12years of age. We
      examined this ability with a task requiring children to navigate a route through
      a model city of wooden blocks from a 90 degrees  and 180 degrees  rotated
      perspective. We tested two hypotheses. First, we hypothesized that children's
      perspective-taking skills increase during this age period and that this process
      is related to a co-occurring increase in working memory capacity. Results indeed
      showed clear age effects; accuracy and speed of perspective-taking performance
      were higher in the older age groups. Positive associations between perspective
      taking performance and working memory were observed. Second, we hypothesized that
      children, like adults, use a mental self-rotation strategy during spatial
      perspective taking. To confirm this hypothesis, children's performance should be
      better in the 90 degrees  condition than in the 180 degrees  condition of the
      task. Overall, the results did show the reversed pattern; children were less
      accurate, were slower, and committed more egocentric errors in the 90 degrees 
      condition than in the 180 degrees  condition. These findings support an
      alternative scenario in which children employ different strategies for different
      rotation angles. We propose that children mentally rotated their egocentric
      reference frame for 90 degrees  rotations; for the 180 degrees  rotations, they
      inverted the left-right and front-back axes without rotating their mental
      position.

PMID- 27689896
TI  - Atlas-based shape analysis and classification of retinal optical coherence
      tomography images using the functional shape (fshape) framework.
AB  - We propose a novel approach for quantitative shape variability analysis in
      retinal optical coherence tomography images using the functional shape (fshape)
      framework. The fshape framework uses surface geometry together with functional
      measures, such as retinal layer thickness defined on the layer surface, for
      registration across anatomical shapes. This is used to generate a population mean
      template of the geometry-function measures from each individual. Shape
      variability across multiple retinas can be measured by the geometrical
      deformation and functional residual between the template and each of the
      observations. To demonstrate the clinical relevance and application of the
      framework, we generated atlases of the inner layer surface and layer thickness of
      the Retinal Nerve Fiber Layer (RNFL) of glaucomatous and normal subjects,
      visualizing detailed spatial pattern of RNFL loss in glaucoma. Additionally, a
      regularized linear discriminant analysis classifier was used to automatically
      classify glaucoma, glaucoma-suspect, and control cases based on RNFL fshape
      metrics.

PMID- 27689897
TI  - Real-time target tracking of soft tissues in 3D ultrasound images based on robust
      visual information and mechanical simulation.
AB  - In this paper, we present a real-time approach that allows tracking deformable
      structures in 3D ultrasound sequences. Our method consists in obtaining the
      target displacements by combining robust dense motion estimation and mechanical
      model simulation. We perform evaluation of our method through simulated data,
      phantom data, and real-data. Results demonstrate that this novel approach has the
      advantage of providing correct motion estimation regarding different ultrasound
      shortcomings including speckle noise, large shadows and ultrasound gain
      variation. Furthermore, we show the good performance of our method with respect
      to state-of-the-art techniques by testing on the 3D databases provided by MICCAI
      CLUST'14 and CLUST'15 challenges.

PMID- 27689898
TI  - Hostility and telomere shortening among U.S. military veterans: Results from the
      National Health and Resilience in Veterans Study.
AB  - : Chronic disorders of aging are critical concerns for the U.S. veteran
      population, which is, on average, two decades older than the non-veteran
      population. Characterization of risk factors that may accelerate biological aging
      is important in identifying targets for prevention and intervention. In the
      current study, we analyzed data from a contemporary, and nationally
      representative sample of U.S. veterans to evaluate the relationship between a
      broad range of sociodemographic, military, and clinical variables, and peripheral
      telomere length, which is an indicator of biological age and linked to risk for
      aging-related disorders and mortality. Data from 468U.S. military veterans who
      participated in the National Health and Resilience in Veterans Study were
      analyzed. Telomere length was assessed from cells isolated from saliva using
      quantitative polymerase chain reaction methods. A multivariable binary logistic
      regression analysis was conducted to evaluate the relations between hostility and
      telomere length, while controlling for sociodemographic, military, and clinical
      variables. Greater scores on a measure of hostility were independently associated
      with telomere shortening, even after adjustment for a broad range of other
      variables (odds ratio [OR]=1.58, 95% confidence interval [CI]=1.15-2.18).
      Secondary analyses revealed that this association was driven by difficulties
      controlling anger (OR=1.72, 95%CI=1.14-2.61), which reflect the external
      manifestation of hostility, rather than aggressive urges or impulses. Hostility,
      particularly difficulties controlling anger, is associated with peripheral
      telomere shortening in U.S. military veterans. Prevention and treatment efforts
      designed to reduce hostility may help mitigate risk for accelerated cellular
      aging in this growing segment of the U.S. POPULATION: 

PMID- 27689899
TI  - Sleep restriction alters plasma endocannabinoids concentrations before but not
      after exercise in humans.
AB  - Following binding to cannabinoid receptors, endocannabinoids regulate a variety
      of central nervous system processes including appetite and mood. Recent evidence
      suggests that the systemic release of these lipid metabolites can be altered by
      acute exercise and that their levels also vary across the 24-h sleep-wake cycle.
      The present study utilized a within-subject design (involving 16 normal-weight
      men) to determine whether daytime circulating endocannabinoid concentrations
      differ following three nights of partial sleep deprivation (4.25-h sleep
      opportunity, 2:45-7a.m. each night) vs. normal sleep (8.5-h sleep opportunity,
      10:30p.m.-7a.m. each night), before and after an acute bout of ergometer cycling
      in the morning. In addition, subjective hunger and stress were measured. Pre
      exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher
      1.5h after awakening (vs. normal sleep, p<0.05) when participants were sleep
      deprived. This coincided with increased hunger ratings (+25% vs. normal sleep,
      p<0.05). Moreover, plasma 2AG was elevated 15min post-exercise (+44%, p<0.05).
      Sleep duration did not however modulate this exercise-induced rise. Finally,
      subjective stress was generally lower on the day after three nights of short
      sleep vs. normal sleep, especially after exercise (p<0.05). Given that activation
      of the endocannabinoid system has been previously shown to acutely increase
      appetite and mood, our results could suggest that behavioral effects of acute
      sleep loss, such as increased hunger and transiently improved psychological
      state, may partially result from activation of this signaling pathway. In
      contrast, more pronounced exercise-induced elevations of endocannabinoids appear
      to be less affected by short sleep duration.

PMID- 27689901
TI  - The ability of athletes with long-standing groin pain to maintain a stable
      lumbopelvic position: A laboratory study.
AB  - OBJECTIVES: The ability to maintain a lumbopelvic position (LPP) was assessed in
      athletes with a history of long-standing groin pain (LSGP) and athletes without
      LSGP. DESIGN: Case-control study. SETTING: University motion analysis laboratory.
      PARTICIPANTS: Thirty male athletes-15 with a history of LSGP (>12 weeks) and 15
      without. MAIN OUTCOME MEASURES: Maintenance of LPP was assessed using a pressure
      biofeedback unit (PBU) during supine single leg lift (SLL), single leg extension
      (SLE) and bent knee fallout (BKFO). Repeatability was assessed using intra-class
      correlation coefficients (ICC) and group differences analysed using MANOVA.
      RESULTS: Differences were detected between involved and uninvolved sides in the
      LSGP group during SLL (mean difference [md] = 9.82 mmHg, p < 0.01) and BKFO (md =
      8.56 mmHg, p < 0.01) but not during SLE (md = 0.38 mmHg, p = 0.96). Between group
      differences were found during the SLL of the involved leg (md = 5.22 mmHg p =
      0.034) and the BKFO of the uninvolved leg (md = 6.22 mmHg p = 0.017). Inter
      session reliability varied for the different movement tasks in both groups (ICC =
      0.35-0.94). CONCLUSIONS: Ability to maintain LPP differed between the involved
      and uninvolved legs within the LSGP group and between the athletes with and
      without LSGP. Despite resolution of groin pain, altered control of lumbopelvic
      position existed with possible implications for later injury recurrence.

PMID- 27689900
TI  - Stress management, leukocyte transcriptional changes and breast cancer recurrence
      in a randomized trial: An exploratory analysis.
AB  - PURPOSE: Cognitive behavioral stress management (CBSM) is an empirically
      validated group-based psychosocial intervention. CBSM is related to decreased
      self-reported indicators of psychological adversity during breast cancer
      treatment and greater disease-free survival (DFS) vs. a control condition. This
      study examined relationships between CBSM, DFS, and a potential biobehavioral
      pathway linking these variables in breast cancer patients through a gene
      expression composite representing the leukocyte conserved transcriptional
      response to adversity (CTRA). DESIGN: Women with stage 0-IIIb breast cancer
      completed questionnaires and provided blood samples post-surgery. Participants
      were randomized to 10-week group-based CBSM or a psychoeducation control group
      and followed at 6 months, 12 months, and median 11 years. In total, 51
      participants provided blood data for longitudinal analyses (CBSM n=28; Control
      n=23). Mixed model analyses examined CBSM effects on 6-12 month changes in CTRA
      expression (53 indicator genes representing pro-inflammatory, anti-viral and
      antibody production signaling). Cox regression models assessed the relationship
      between 6 and 12 month changes in CTRA expression and 11-year DFS. RESULTS:
      Patients randomized to CBSM showed attenuated 6-12 month change in CTRA gene
      expression, whereas patients randomized to control showed increased CTRA
      expression (p=0.014). Average DFS was 5.92 years (SD=3.90). Greater 6-12 month
      CTRA increases predicted shorter 11-year DFS controlling for covariates
      (p=0.007). CONCLUSIONS: CBSM attenuated CTRA gene expression during the initial
      year of breast cancer treatment. In turn, greater increases in CTRA gene
      expression predicted shorter long-term DFS. These findings identify a
      biobehavioral oncology pathway to examine in future work.

PMID- 27689903
TI  - Precious-Metal-Free Heteroarylation of Azlactones: Direct Synthesis of alpha
      Pyridyl, alpha-Substituted Amino Acid Derivatives.
AB  - A one-pot, three-component synthesis of alpha-pyridyl, alpha-substituted amino
      acid derivatives is described. The key transformation is a direct, precious-metal
      free heteroarylation of readily available, amino acid derived azlactones with
      electrophilically activated pyridine N-oxides. The resulting intermediates can be
      used directly as efficient acylating agents for a range of nucleophiles, leading
      to the heteroarylated amino acid derivatives in a single vessel.

PMID- 27689904
TI  - Anisotropic Dielectric Breakdown Strength of Single Crystal Hexagonal Boron
      Nitride.
AB  - Dielectric breakdown has historically been of great interest from the
      perspectives of fundamental physics and electrical reliability. However, to date,
      the anisotropy in the dielectric breakdown has not been discussed. Here, we
      report an anisotropic dielectric breakdown strength (EBD) for h-BN, which is used
      as an ideal substrate for two-dimensional (2D) material devices. Under a well
      controlled relative humidity, EBD values in the directions both normal and
      parallel to the c axis (EBD?c and EBD?c) were measured to be 3 and 12 MV/cm,
      respectively. When the crystal structure is changed from sp3 of cubic-BN (c-BN)
      to sp2 of h-BN, EBD?c for h-BN becomes smaller than that for c-BN, while EBD?c
      for h-BN drastically increases. Therefore, h-BN can possess a relatively high EBD
      concentrated only in the direction parallel to the c axis by conceding a weak
      bonding direction in the highly anisotropic crystal structure. This explains why
      the EBD?c for h-BN is higher than that for diamond. Moreover, the presented EBD
      value obtained from the high quality bulk h-BN crystal can be regarded as the
      standard for qualifying the crystallinity of h-BN layers grown via chemical vapor
      deposition for future electronic applications.

PMID- 27689902
TI  - Cell biology of Candida albicans-host interactions.
AB  - Candida albicans is a commensal coloniser of most people and a pathogen of the
      immunocompromised or patients in which barriers that prevent dissemination have
      been disrupted. Both the commensal and pathogenic states involve regulation and
      adaptation to the host microenvironment. The pathogenic potential can be
      downregulated to sustain commensalism or upregulated to damage host tissue and
      avoid and subvert immune surveillance. In either case it seems as though the cell
      biology of this fungus has evolved to enable the establishment of different types
      of relationships with the human host. Here we summarise latest advances in the
      analysis of mechanisms that enable C. albicans to occupy different body sites
      whilst avoiding being eliminated by the sentinel activities of the human immune
      system.

PMID- 27689906
TI  - Aqueous Synthesis of (210) Oxygen-Terminated Defect-Free Hierarchical ZnO
      Particles and Their Heat Treatment for Enhanced Reactivity.
AB  - Controlled aqueous growth of 1 MUm flower-shaped ZnO particles with a
      hierarchical subset of exposed nanosheets represented by {210} crystal faces,
      followed by annealing at temperatures up to 1000  degrees C, is presented. The
      flower-shaped particles showed superior photocatalytic performance compared to
      the crystal faces of 20 nm ZnO nanoparticles. The photocatalytic reaction rate of
      the flower-shaped particles before annealing was 2.4 times higher per m2 compared
      with that of the nanoparticles with double specific surface area. Crystal surface
      defects and nanosized pores within the flower-shaped particles were revealed by
      porosity measurements and electron microscopy. A heat treatment at 400  degrees C
      was found to be optimal for removal of nanoporosity/surface defects and
      impurities while retaining the hierarchical superstructure. The heat treatment
      resulted in a photodegradation efficiency that increased by an additional 43%,
      although the specific surface area decreased from 16.7 to 13.0 m2g-1. The
      enhanced photocatalytic effect remained intact under both acidic and alkaline
      environments owing to the {210} crystal surfaces, which were less prone to
      dissolution than the nanoparticles. The photocatalytic performance relied on
      primarily three factors: the removal of surface impurities, the oxygen
      termination of the {210} crystal faces, and the promotion of charge carrier
      lifetime by removal of lattice defects acting as recombination centers. The
      synthesis presented is an entirely hydrocarbon- and surfactant-free ("green")
      preparation scheme, and the formation of the flower-shaped particles was favored
      solely by optimization of the reaction temperature after the correct nitrate salt
      precursor concentrations had been established.

PMID- 27689905
TI  - Enhanced non-invasive respiratory sampling from bottlenose dolphins for breath
      metabolomics measurements.
AB  - Chemical analysis of exhaled breath metabolites is an emerging alternative to
      traditional clinical testing for many physiological conditions. The main
      advantage of breath analysis is its inherent non-invasive nature and ease of
      sample collection. Therefore, there exists a great interest in further
      development of this method for both humans and animals. The physiology of
      cetaceans is exceptionally well suited for breath analysis due to their explosive
      breathing behavior and respiratory tract morphology. At the present time, breath
      analysis in cetaceans has very limited practical applications, in large part due
      to lack of widely adopted sampling device(s) and methodologies that are well
      standardized. Here, we present an optimized design and the operating principles
      of a portable apparatus for reproducible collection of exhaled breath condensate
      from small cetaceans, such as bottlenose dolphins (Tursiops truncatus). The
      device design is optimized to meet two criteria: standardized collection and
      preservation of information-rich metabolomic content of the biological sample,
      and animal comfort and ease of breath sample collection. The intent is to furnish
      a fully-benchmarked technology that can be widely adopted by researchers and
      conservationists to spur further developments of breath analysis applications for
      marine mammal health assessments.

PMID- 27689907
TI  - Irida-beta-ketoimines Derived from Hydrazines To Afford Metallapyrazoles or N-N
      Bond Cleavage: A Missing Metallacycle Disclosed by a Theoretical and Experimental
      Study.
AB  - Unprecedented metallapyrazoles [IrH2{Ph2P(o-C6H4)CNNHC(o-C6H4)PPh2}] (3) and
      [IrHCl{Ph2P(o-C6H4)CNNHC(o-C6H4)PPh2}] (4) were obtained by the reaction of the
      irida-beta-ketoimine [IrHCl{(PPh2(o-C6H4CO))(PPh2(o-C6H4CNNH2))H}] (2) in MeOH
      heated at reflux in the presence and absence of KOH, respectively. In solution,
      iridapyrazole 3 undergoes a dynamic process due to prototropic tautomerism with
      an experimental barrier for the exchange of DeltaGcoal? = 53.7 kJ mol-1. DFT
      calculations agreed with an intrapyrazole proton transfer process assisted by two
      water molecules (DeltaG = 63.1 kJ mol-1). An X-ray diffraction study on 4
      indicated electron delocalization in the iridapyrazole ring. The reaction of the
      irida-beta-diketone [IrHCl{(PPh2(o-C6H4CO))2H}] (1) with H2NNRR' in aprotic
      solvents gave irida-beta-ketoimines [IrHCl{(PPh2(o-C6H4CO))(PPh2(o
      C6H4CNNRR'))H}] (R = R' = Me (5); R = H, R' = Ph (8)), which can undergo N-N bond
      cleavage to afford the acyl-amide complex [IrHCl(PPh2(o-C6H4CO))(PPh2(o
      C6H4C(O)N(CH3)2))-kappaP,kappaO] (6) or [IrHCl(PPh2(o-C6H4CO))(PPh2(o-C6H4CN)
      kappaP)(NH2NHPh-kappaNH2)] (9) containing o-(diphenylphosphine)benzonitrile and
      phenylhydrazine, respectively. From a CH2Cl2/CH3OH solution of 9 kept at -18 
      degrees C, single crystals of [IrHCl(PPh2(o-C6H4CO))(PPh2(o-C6H4CN)
      kappaP))(HN?NPh-kappaNH)] (10) containing o-(diphenylphosphine)benzonitrile and
      phenyldiazene were formed, as shown by X-ray diffraction. The reaction of 1 with
      methylhydrazine in methanol gave the hydrazine complex [IrCl(PPh2(o
      C6H4CO))2(NH2NH(CH3)-kappaNH2)] (7). Single-crystal X-ray diffraction analysis
      was performed on 6 and 7.

PMID- 27689908
TI  - Determination and evaluation of heavy metals in soils under two different
      greenhouse vegetable production systems in eastern China.
AB  - The evaluation of heavy metals (HMs) in greenhouse soils is crucial for both
      environmental monitoring and human health; thus, it is imperative to determine
      their concentrations, identify their sources and assess their potential risks. In
      this study, eight metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in 167 surface
      soils were investigated in two representative greenhouse vegetable systems of
      China: perennial solar greenhouse (SG) and seasonal plastic greenhouse (PG). The
      results indicated accumulations of Cd, Cu, Hg and Zn in the SG soils and Cd, Pb,
      Hg and Zn in the PG soils, with higher concentrations than the background values.
      In particular, Cd and Hg exhibited high levels of pollution under both GVP
      systems due to their positive Igeo values. Principle component analysis (PCA) and
      correlation analysis suggested that Cd, Cu, Hg and Zn in the SG soils and Cd, Hg
      and Zn in the PG soils were mainly related to intensive farming practices; Pb in
      the PG soils was significantly affected by atmospheric deposition. The results
      showed that soil characteristics, in particular soil organic matter, total
      nitrogen and total phosphorus, exerted significant influence on Hg, Cu, Cd, and
      Zn under the SG system. However, the HMs in the PG soils were weakly affected by
      soil properties. Overall, this study provides comparative research on the
      accumulation, potential risks and sources of HMs in two typical greenhouse soils
      in China, and our findings suggest that, Cd and Hg in both greenhouse soils could
      potentially represent environmental problems.

PMID- 27689910
TI  - Synthesis, Electrochemical Characterization, and Linear Free Energy Relationship
      of 1,3-Diphenyl-6-alkyl/arylfulvenes.
AB  - A series of 1,3-diphenyl-6-alkyl/arylfulvenes was prepared, and the
      electrochemical properties were investigated. The addition of phenyl groups about
      the fulvene raised the reduction potential and helped to stabilize the
      electrochemically generated radical anion. The addition of various functional
      groups onto the phenyl ring at the 6-position of 1,3,6-triphenylfulvene results
      in a linear free energy relationship between reduction potential and the Hammett
      substituent constant, sigma. Further extending the conjugation at the 6-position
      of 1,3-diphenyl-6-arylfulvenes increases the reversibility of the redox
      reactions, but does not appear to further stabilize the generated radical anion.
      This in-depth investigation provides evidence that the compounds studied may have
      utility in light-harvesting applications.

PMID- 27689909
TI  - Malaria - how this parasitic infection aids and abets EBV-associated Burkitt
      lymphomagenesis.
AB  - Burkitt lymphoma (BL) is >90% EBV-associated when this pediatric cancer is
      diagnosed in regions heavily burden by endemic Plasmodium falciparum malaria and
      thus has been geographically classified as endemic BL. The incidence of endemic
      BL is 10-fold higher compared to BL diagnosed in non-malarious regions of the
      world. The other forms of BL have been classified as sporadic BL which contain
      EBV in ~30% of cases and immunodeficiency BL which occurs in HIV-infected adults
      with ~40% of tumors containing EBV. Within malaria endemic regions, epidemiologic
      studies replicating Denis Burkitt's seminal observation continue to show
      differences in endemic BL incidence linked to intensity of malaria transmission.
      However, the mechanisms by which malaria contributes to B cell tumorigenesis have
      not been resolved to the point of designing cancer prevention strategies. The
      focus of this review is to summarize our current knowledge regarding the
      influence of prolonged, chronic malaria exposure on defects in immunosurveillance
      that would otherwise control persistent EBV infections. And thus, set the stage
      for ensuing mechanisms by which malaria could instigate B cell activation and
      aberrant activation-induced cytidine deaminase expression initiating somatic
      hypermutation and thereby increasing the likelihood of an Ig/Myc translocation,
      the hallmark of all BL tumors. Malaria appears to play multiple, sequential and
      simultaneous roles in endemic BL etiology; the complexity of these interactions
      are being revealed by applying computational methods to human immunology.
      Remaining questions yet to be addressed and prevention strategies will also be
      discussed.

PMID- 27689911
TI  - Electrochemically Induced Transformations of Vanadium Dioxide Nanocrystals.
AB  - Vanadium dioxide (VO2) undergoes significant optical, electronic, and structural
      changes as it transforms between the low-temperature monoclinic and high
      temperature rutile phases. Recently, alternative stimuli have been utilized to
      trigger insulator-to-metal transformations in VO2, including electrochemical
      gating. Here, we prepare and electrochemically reduce mesoporous films of VO2
      nanocrystals, prepared from colloidally synthesized V2O3 nanocrystals that have
      been oxidatively annealed, in a three-electrode electrochemical cell. We observe
      a reversible transition between infrared transparent insulating phases and a
      darkened metallic phase by in situ visible-near-infrared spectroelectrochemistry
      and correlate these observations with structural and electronic changes monitored
      by X-ray absorption spectroscopy, X-ray diffraction, Raman spectroscopy, and
      conductivity measurements. An unexpected reversible transition from conductive,
      reduced monoclinic VO2 to an infrared-transparent insulating phase upon
      progressive electrochemical reduction is observed. This insulator-metal-insulator
      transition has not been reported in previous studies of electrochemically gated
      epitaxial VO2 films and is attributed to improved oxygen vacancy formation
      kinetics and diffusion due to the mesoporous nanocrystal film structure.

PMID- 27689913
TI  - Toward a Better Beauty Regimen: Reducing Potential EDC Exposures from Personal
      Care Products.

PMID- 27689912
TI  - Antivirulence C-Mannosides as Antibiotic-Sparing, Oral Therapeutics for Urinary
      Tract Infections.
AB  - Gram-negative uropathogenic Escherichia coli (UPEC) bacteria are a causative
      pathogen of urinary tract infections (UTIs). Previously developed antivirulence
      inhibitors of the type 1 pilus adhesin, FimH, demonstrated oral activity in
      animal models of UTI but were found to have limited compound exposure due to the
      metabolic instability of the O-glycosidic bond (O-mannosides). Herein, we
      disclose that compounds having the O-glycosidic bond replaced with carbon
      linkages had improved stability and inhibitory activity against FimH. We report
      on the design, synthesis, and in vivo evaluation of this promising new class of
      carbon-linked C-mannosides that show improved pharmacokinetic (PK) properties
      relative to O-mannosides. Interestingly, we found that FimH binding is
      stereospecifically modulated by hydroxyl substitution on the methylene linker,
      where the R-hydroxy isomer has a 60-fold increase in potency. This new class of C
      mannoside antagonists have significantly increased compound exposure and, as a
      result, enhanced efficacy in mouse models of acute and chronic UTI.

PMID- 27689914
TI  - Can Neuroimaging Markers of Vascular Pathology Explain Cognitive Performance in
      Adults With Sickle Cell Anemia? A review of the Literature.
AB  - Adults with homozygous sickle cell anemia have, on average, lower cognitive
      function than unaffected controls. The mechanisms underlying cognitive
      deterioration in this population are poorly understood, but cerebral small vessel
      disease (CSVD) is likely to be implicated. We conducted a systematic review using
      the Prisma Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines of articles that included both measures of cognitive function and
      magnetic resonance imaging (MRI) neuroimaging markers of small vessel disease.
      While all five studies we identified reported small vessel disease by MRI, only
      two of them found a significant relationship between structural changes and
      cognitive performance. Differences in methodologies and small sample sizes likely
      accounted for the discrepancies between the studies. We conclude that while MRI
      is a valuable tool to identify markers of CSVD in this population, larger studies
      are needed to definitely establish a link between MRI-detectable abnormalities
      and cognitive function in sickle cell anemia.

PMID- 27689916
TI  - A novel puborectalis muscle artificial anal sphincter system with the module of
      sensory perception.
AB  - This article presents a novel puborectalis muscle artificial anal sphincter
      system (PM-AASS) with the module of sensory perception for treating severe faecal
      incontinence (FI). Due to the implantable feature of PM-AASS, this system applied
      low-power design and the total energy consumption could drop to 48.8 Ah/d. To
      reduce the injury of intestine and the pressure exerted on intestine, the
      actuator, including the structure of tings and the robot mechanism, of PM-AASS
      was presented and the middle ring was optimised. To realise the sensory
      perception, the intestinal flexible pressure sensors, comprising the radial
      sensors and the axial sensors, were designed. The sensors calibration showed the
      R-square of each fitting line were above 0.998, which presented a high goodness
      of fit and indicated we could figure out the pressure value with the analogue
      voltage captured by MCU. Through the in-vitro experiment, the results that the
      radial sensors were more relevant to the occlusion threshold while the axial
      sensors had more effect on the alarm threshold could be concluded. The
      practicability of the PM-AASS was verified by the results of the in-vivo
      experiment, which showed that the PM-AASS had the effect of improvement to the
      anorectal internal pressure.

PMID- 27689915
TI  - In silico frameworks for systematic pre-clinical screening of potential anti
      leukemia therapeutics.
AB  - INTRODUCTION: Leukemia is a collection of highly heterogeneous cancers that arise
      from neoplastic transformation and clonal expansion of immature hematopoietic
      cells. Post-treatment recurrence is high, especially among elderly patients, thus
      necessitating more effective treatment modalities. Development of novel anti
      leukemic compounds relies heavily on traditional in vitro screens which require
      extensive resources and time. Therefore, integration of in silico screens prior
      to experimental validation can improve the efficiency of pre-clinical drug
      development. Areas covered: This article reviews different methods and frameworks
      used to computationally screen for anti-leukemic agents. In particular, three
      approaches are discussed including molecular docking, transcriptomic integration,
      and network analysis. Expert opinion: Today's data deluge presents novel
      opportunities to develop computational tools and pipelines to screen for likely
      therapeutic candidates in the treatment of leukemia. Formal integration of these
      methodologies can accelerate and improve the efficiency of modern day anti
      leukemic drug discovery and ease the economic and healthcare burden associated
      with it.

PMID- 27689917
TI  - Generating Aptamers Interacting with Polymeric Surfaces for Biofunctionalization.
AB  - Common strategies for biofunctionalization of surfaces comprise the
      immobilization of bioactive molecules used as cell-binding ligands for cell
      recruitment. Besides covalent binding, multivalent noncovalent physical forces
      between substrate and ligand are an alternative way to equip surfaces with
      biomacromolecules. In this study, polymer binding ligands are screened by means
      of a DNA-based in vitro selection process. As candidate biomaterials poly(ether
      imide) (PEI), polystyrene, and poly[ethylene-co-(vinyl acetate)] are selected,
      due to their different chemical structure, but similar macroscopic interface
      properties, allowing physical interaction with nucleotide bases by varying
      valences. Multivalent interacting aptamers are successfully enriched by SELEX
      method and an area-wide surface functionalization is achieved, which can be used
      for further binding of bioactive molecules. In vitro selection against the
      polymers result in thymine-dominated aptamer binding motifs. The preferential
      interaction with thymine is attributed to its chemical structure, connected with
      a decreased electrostatic repulsion of the pi-system and the hydrophobic
      character maximizing entropy. The aptamer binding stability correlates with
      available valences for interaction, resulting in a more stable functionalization
      of PEI.

PMID- 27689918
TI  - Treatment response of ethyl pyruvate in a mouse model of chronic obstructive
      pulmonary disease studied by hyperpolarized 129 Xe MRI.
AB  - PURPOSE: The purpose of this work was to investigate disease progression and
      treatment response in a murine model of chronic obstructive pulmonary disease
      (COPD) using a preclinical hyperpolarized 129 Xe (HPXe) magnetic resonance
      imaging (MRI) strategy. METHODS: COPD phenotypes were induced in 32 mice by 10
      weeks of exposure to cigarette smoke (CS) and lipopolysaccharide (LPS). Efficacy
      of ethyl pyruvate (EP), an anti-inflammatory drug, was investigated by
      administering EP to 16 of the 32 mice after 6 weeks of CS and LPS exposure. HPXe
      MRI was performed to monitor changes in pulmonary function during disease
      progression and pharmacological therapy. RESULTS: HPXe metrics of fractional
      ventilation and gas-exchange function were significantly reduced after 6 weeks of
      CS and LPS exposure compared to sham-instilled mice administered with saline (P <
      0.05). After this observation, EP administration was started in 16 of the 32 mice
      and continued for 4 weeks. EP was found to improve HPXe MRI metrics to a similar
      level as in sham-instilled mice (P < 0.01). Histological analysis showed
      significant alveolar tissue destruction in the COPD group, but relatively normal
      alveolar structure in the EP and sham-instilled groups. CONCLUSION: This study
      demonstrates the potential efficacy of EP for COPD therapy, as assessed by a
      noninvasive, translatable 129 Xe MRI procedure. Magn Reson Med 78:721-729, 2017.
      (c) 2016 International Society for Magnetic Resonance in Medicine.

PMID- 27689920
TI  - Toehold-Mediated Displacement of an Adenosine-Binding Aptamer from a DNA Duplex
      by its Ligand.
AB  - DNA is increasingly used to engineer dynamic nanoscale circuits, structures, and
      motors, many of which rely on DNA strand-displacement reactions. The use of
      functional DNA sequences (e.g., aptamers, which bind to a wide range of ligands)
      in these reactions would potentially confer responsiveness on such devices, and
      integrate DNA computation with highly varied molecular stimuli. By using high
      throughput single-molecule FRET methods, we compared the kinetics of a putative
      aptamer-ligand and aptamer-complement strand-displacement reaction. We found that
      the ligands actively disrupted the DNA duplex in the presence of a DNA toehold in
      a similar manner to complementary DNA, with kinetic details specific to the
      aptamer structure, thus suggesting that the DNA strand-displacement concept can
      be extended to functional DNA-ligand systems.

PMID- 27689919
TI  - Tethered capsule endomicroscopy: from bench to bedside at a primary care
      practice.
AB  - Due to the relatively high cost and inconvenience of upper endoscopic biopsy and
      the rising incidence of esophageal adenocarcinoma, there is currently a need for
      an improved method for screening for Barrett's esophagus. Ideally, such a test
      would be applied in the primary care setting and patients referred to endoscopy
      if the result is suspicious for Barrett's. Tethered capsule endomicroscopy (TCE)
      is a recently developed technology that rapidly acquires microscopic images of
      the entire esophagus in unsedated subjects. Here, we present our first experience
      with clinical translation and feasibility of TCE in a primary care practice. The
      acceptance of the TCE device by the primary care clinical staff and patients
      shows the potential of this device to be useful as a screening tool for a broader
      population.

PMID- 27689921
TI  - Diagnosis of Vein of Galen aneurysmal malformation using fetal MRI.
AB  - PURPOSE: To present three fetal vein of Galen aneurysmal malformations (VGAMs),
      which were diagnosed through magnetic resonance imaging (MRI), and highlight
      these cardiovascular findings. MATERIALS AND METHODS: We retrospectively reviewed
      three fetuses with VGAM at 31, 32, and 33 weeks of gestation. Feeding arteries
      and draining veins were observed by MRI. Secondary changes in the brain and high
      output heart failure caused by high blood flow in the lesion were evaluated. Two
      fetuses were born, and neonatal MRI was performed. One fetus was terminated.
      RESULTS: A characteristic dilated structure in the midline of the brain presented
      in each fetus. The arteriovenous fistula led to anatomical brain changes such as
      in the hydrocephalus, dilated feeding vessels (one or more), jugular vein, and/or
      superior vena cava. Substantial brachiocephalic vessel dilation was observed in
      two fetuses. Following parturition, one baby had neonatal asphyxia and sinus
      thrombosis, and MRI revealed hypoxic-ischemic encephalopathy. Cardiomegaly was
      detected in all three cases. CONCLUSION: With a large field of view, fetal MRI
      can observe brain VGAM, as well as the heart and affected large vessels. It can
      determine hydrocephalus, ischemia, intracranial hemorrhage, and sinus thrombosis.
      Providing such information on the infant's entire body can aid clinicians in
      determining the most appropriate treatment. LEVEL OF EVIDENCE: 4 J. Magn. Reson.
      Imaging 2017;46:1535-1539.

PMID- 27689923
TI  - Cervical Spondylotic Myelopathy: Metabolite Changes in the Primary Motor Cortex
      after Surgery.
AB  - Purpose To characterize longitudinal metabolite alterations in the motor cortex
      of patients with cervical spondylotic myelopathy (CSM) by using proton magnetic
      resonance (MR) spectroscopy and to evaluate white matter integrity with diffusion
      tensor imaging in patients who are recovering neurologic function after
      decompression surgery. Materials and Methods Informed written consent was
      obtained for all procedures and the study was approved by Western University's
      Health Sciences Research Ethics Board. Twenty-eight patients with CSM and 10
      healthy control subjects were prospectively recruited and underwent two separate
      3-T MR imaging examinations 6 months apart. Patients with CSM underwent surgery
      after the first examination. N-acetylaspartate (NAA), an indicator of neuronal
      mitochondrial function, normalized to creatine (Cr) levels were measured from the
      motor cortex contralateral to the greater functional deficit side in the patient
      group and on both sides in the control group. Fractional anisotropy and mean
      diffusivity were measured by means of diffusion-tensor imaging in the white
      matter adjacent to the motor and sensory cortices of the hand and the entire
      cerebral white matter. Clinical data were analyzed by using Student t tests.
      Results In patients with CSM, NAA normalized to Cr (NAA/Cr) levels were
      significantly lower 6 months after surgery (1.48 +/- 0.08; P < .03) compared with
      preoperative levels (1.73 +/- 0.09), despite significant improvement in clinical
      questionnaire scores. Fractional anisotropy and mean diffusivity were the same (P
      > .05) between the patient and control groups in all measured regions at all time
      points. Conclusion NAA/Cr levels decreased in the motor cortex in patients with
      CSM 6 months after successful surgery. Intact white matter integrity with
      decreased NAA/Cr levels suggests that mitochondrial metabolic dysfunction
      persists after surgery. (c) RSNA, 2016 Online supplemental material is available
      for this article.

PMID- 27689922
TI  - Yield of CT Pulmonary Angiography in the Emergency Department When Providers
      Override Evidence-based Clinical Decision Support.
AB  - Purpose To determine the frequency of, and yield after, provider overrides of
      evidence-based clinical decision support (CDS) for ordering computed tomographic
      (CT) pulmonary angiography in the emergency department (ED). Materials and
      Methods This HIPAA-compliant, institutional review board-approved study was
      performed at a tertiary care, academic medical center ED with approximately 60
      000 annual visits and included all patients who were suspected of having
      pulmonary embolism (PE) and who underwent CT pulmonary angiography between
      January 1, 2011, and August 31, 2013. The requirement to obtain informed consent
      was waived. Each CT order for pulmonary angiography was exposed to CDS on the
      basis of the Wells criteria. For patients with a Wells score of 4 or less, CDS
      alerts suggested d-dimer testing because acute PE is highly unlikely in these
      patients if d-dimer levels are normal. The yield of CT pulmonary angiography
      (number of positive PE diagnoses/total number of CT pulmonary angiographic
      examinations) was compared in patients in whom providers overrode CDS alerts (by
      performing CT pulmonary angiography in patients with a Wells score <=4 and a
      normal d-dimer level or no d-dimer testing) (override group) and those in whom
      providers followed Wells criteria (CT pulmonary angiography only in patients with
      Wells score >4 or <=4 with elevated d-dimer level) (adherent group). A validated
      natural language processing tool identified positive PE diagnoses, with
      subsegmental and/or indeterminate diagnoses removed by means of chart review.
      Statistical analysis was performed with the chi2 test, the Student t test, and
      logistic regression. Results Among 2993 CT pulmonary angiography studies in 2655
      patients, 563 examinations had a Wells score of 4 or less but did not undergo d
      dimer testing and 26 had a Wells score of 4 or less and had normal d-dimer
      levels. The yield of CT pulmonary angiography was 4.2% in the override group (25
      of 589 studies, none with a normal d-dimer level) and 11.2% in the adherent group
      (270 of 2404 studies) (P < .001). After adjustment for the risk factor
      differences between the two groups, the odds of an acute PE finding were 51.3%
      lower when providers overrode alerts than when they followed CDS guidelines.
      Comparison of the two groups including only patients unlikely to have PE led to
      similar results. Conclusion The odds of an acute PE finding in the ED when
      providers adhered to evidence presented in CDS were nearly double those seen when
      providers overrode CDS alerts. Most overrides were due to the lack of d-dimer
      testing in patients unlikely to have PE. (c) RSNA, 2016.

PMID- 27689924
TI  - Impact of in Vivo High-Field-Strength and Ultra-High-Field-Strength MR Imaging on
      DNA Double-Strand-Break Formation in Human Lymphocytes.
AB  - Purpose To determine the impact of different magnetic field strengths (1, 1.5, 3,
      and 7 T) and the effect of contrast agent on DNA double-strand-break (DSB)
      formation in patients undergoing magnetic resonance (MR) imaging. Materials and
      Methods This in vivo study was approved by the local ethics committee, and
      written informed consent was obtained from each patient. To analyze the level of
      DNA DSBs, peripheral blood mononuclear cells were isolated from blood samples
      drawn directly before, as well as 5 minutes and 30 minutes after MR imaging
      examination. After performing gammaH2AX immunofluorescence staining, DSBs were
      quantified with automated digital microscopy. MR group consisted of 43 patients
      (22 women, 21 men; mean age, 46.1 years; range, 20-77 years) and was further
      subdivided according to the applied field strength and administration of contrast
      agent. Additionally, 10 patients undergoing either unenhanced or contrast
      material-enhanced computed tomography (CT) served as positive control subjects.
      Statistical analysis was performed with Friedman test. Results Whereas DSBs in
      lymphocytes increased after CT exposure (before MR imaging: 0.14 foci per cell +/
      0.05; 5 minutes after: 0.26 foci per cell +/- 0.07; 30 minutes after: 0.24 foci
      per cell +/- 0.07; P <= .05), no alterations were observed in patients examined
      with MR imaging (before MR imaging: 0.13 foci per cell +/- 0.02; 5 minutes after:
      0.12 foci per cell +/- 0.02; 30 minutes after: 0.11 foci per cell +/- 0.02; P >
      .05). Differentiated analysis of MR imaging subgroups again revealed no
      significant changes in gammaH2AX level. Conclusion Analysis of gammaH2AX foci
      showed no evidence of DSB induction after MR examination, independent of the
      applied field strength and administration of gadolinium-based contrast agent.

PMID- 27689925
TI  - Internal Hernia after Laparoscopic Roux-en-Y Gastric Bypass: Optimal CT Signs for
      Diagnosis and Clinical Decision Making.
AB  - Purpose To evaluate the accuracy of computed tomography (CT) for diagnosis of
      internal hernia (IH) in patients who have undergone laparoscopic Roux-en-Y
      gastric bypass and to develop decision tree models to optimize diagnostic
      accuracy. Materials and Methods This was a retrospective, ethics-approved study
      of patients who had undergone laparoscopic Roux-en-Y gastric bypass with
      surgically confirmed IH (n = 76) and without IH (n = 78). Two radiologists
      independently reviewed each examination for the following previously established
      CT signs of IH: mesenteric swirl, small-bowel obstruction (SBO), mushroom sign,
      clustered loops, hurricane eye, small bowel behind the superior mesenteric
      artery, and right-sided anastomosis. Radiologists also evaluated images for two
      new signs, superior mesenteric vein (SMV) "beaking" and "criss-cross" of the
      mesenteric vessels. Overall impressions for diagnosis of IH were recorded.
      Diagnostic accuracy and interobserver agreement were calculated, and multivariate
      recursive partitioning was performed to evaluate various decision tree models by
      using the CT signs. Results Accuracy and interobserver agreement regarding the
      nine CT signs of IH showed considerable variation. The best signs were mesenteric
      swirl (sensitivity and specificity, 86%-89% and 86%-90%, respectively; kappa =
      0.74) and SMV beaking (sensitivity and specificity, 80%-88% and 94%-95%,
      respectively; kappa = 0.83). Overall reader impression yielded the highest
      sensitivity and specificity (96%-99% and 90%-99%, respectively; kappa = 0.79).
      The decision tree model with the highest overall accuracy and sensitivity
      included mesenteric swirl and SBO, with a diagnostic odds ratio of 154 (95%
      confidence interval [CI]: 146, 161), sensitivity of 96% (95% CI: 87%, 99%), and
      specificity of 87% (95% CI: 75%, 93%). The decision tree with the highest
      specificity included SMV beaking and SBO, with a diagnostic odds ratio of 105
      (95% CI: 101, 109), sensitivity of 90% (95% CI: 79%, 95%), and specificity of 92%
      (95% CI: 83%, 97%). Conclusion The decision tree with the highest accuracy and
      sensitivity for diagnosis of IH included mesenteric swirl and SBO, the model with
      the highest specificity included SMV beaking and SBO, and the remaining signs
      showed lower accuracy and/or poor to fair interobserver agreement. Overall reader
      impression yielded the highest accuracy for diagnosis of IH, likely because
      alternate diagnoses not incorporated in the models were considered. (c) RSNA,
      2016 Online supplemental material is available for this article.

PMID- 27689927
TI  - The Use of Direct Composite.

PMID- 27689928
TI  - Operative Dentistry in a Changing Dental Health Care Environment.

PMID- 27689929
TI  - When and How to Intervene in the Caries Process.
AB  - The decrease in caries prevalence in many industrialized countries and the
      improved knowledge about the etiology and pathogenesis of caries have shifted the
      focus of caries therapy over the past decades toward less invasive approaches.
      Studies on caries progression indicate that it is generally quite slow in most
      patients today which should lead to a reconsideration of the practice of early
      invasive intervention. Today noninvasive (eg, fluorides) and microinvasive
      (occlusal sealing, proximal infiltration) therapeutic options that address
      etiological factors are gaining importance. The goal of these therapies is to
      heal or at least to slow down the progress of the disease. Noninvasive treatments
      are mainly related to controlling pathogenic factors (ie, sugar consumption) and
      enhancing protective factors (mainly oral hygiene and fluorides). Microinvasive
      treatments do not rely on the compliance of the patient as much, since these
      treatments include a resinous material that is applied to serve as a diffusion
      barrier for acids formed by cariogenic bacteria in the overlying plaque. To
      establish a minimum intervention treatment strategy for caries, the disease must
      be diagnosed at an early stage. In addition to assessing caries lesions in single
      teeth, individual risk factors need to be identified so that the underlying
      causes related to patients' behavioral patterns that led to the disease can be
      addressed as well. The patient should be informed about the scientific evidence
      related to the treatment choices in a participative atmosphere. Decision trees
      may help to make the range of findings comprehensible and the therapeutic shared
      decision-making process understandable to the patients.

PMID- 27689930
TI  - Criteria for the Replacement of Restorations: Academy of Operative Dentistry
      European Section.
AB  - The replacement of a restoration is one of the most common procedures in
      dentistry. However, the criteria for such intervention, excluding catastrophic
      failure and persistent discomfort and pain, continue to be the subject of
      considerable debate. The decision-making process remains subjective on the part
      of the treating clinician, while the evidence base for refurbishment and repair
      rather than replacement for the management of defective and failing restorations
      continues to grow and strengthen. This article, prepared as an Academy of
      Operative Dentistry European Section consensus publication, reviews existing
      criteria for the replacement of restorations and encourages practitioners to
      shift, if not already doing so, to considering the replacement of a restoration
      as a last resort rather than as a prudent action to be taken if in any doubt
      about clinical acceptability. Further research in the area, spanning the risk
      assessment of defective and failing restorations and new diagnostic tools and
      processes, together with work to enhance the evidence base of restoration repair
      vs replacement, would be of immense value.

PMID- 27689931
TI  - Restoration Survival: Revisiting Patients' Risk Factors Through a Systematic
      Literature Review.
AB  - A literature review was conducted to investigate the influence of patient-related
      factors on restoration survival in posterior permanent teeth as well as to report
      the methods used to collect these factors. The selection of articles on
      longitudinal clinical studies investigating the survival of posterior
      restorations (except full crowns and temporary fillings) and including patient
      related factors was performed by applying predefined criteria. The review was
      organized into two parts, the first describing how patient factors were assessed
      in the studies (n=45) and the second presenting the statistical significance
      (n=27) and size of the effect (n=11) of these factors on restoration survival.
      Patient-related factors mentioned in the studies included age; gender; caries
      risk; caries activity/severity; decayed, missing, filled teeth; number of
      restorations; oral hygiene; and bruxism, among others. Sixteen studies included
      the patient age or age range in the analysis, which was found to be significant
      in 47% of the studies. Regarding gender, four of 17 reports found a significant
      effect on survival, showing more failures for men in three studies. The caries
      risk profile or related variables were included in the analysis of 15 studies,
      and a significant effect on survival was reported for high-caries-risk
      individuals (or related variables) in 67% of these studies. Bruxism was also
      found to influence restoration survival in three of six studies where this
      variable was investigated. Some issues were found regarding the reporting of
      methods used to classify patients according to risk and were thoroughly
      discussed. In view of the information gathered in this review, the assessment of
      patient factors along with other variables should become part of clinical studies
      investigating restoration survival, since several of these factors were shown to
      influence the failure of restorations, regardless of the material type.

PMID- 27689932
TI  - Professional Variability in Decision Making in Modern Dentistry: A Pilot Study.
AB  - Dental treatment planning is usually expected to take account of the individual
      patient's clinical risks and benefits. Ideally, the therapeutic choice for each
      and every patient should be based on adequate clinical diagnostics and risk
      assessment that facilitates stabilization of the patient's clinical condition as
      well as prevents further oral impairment. However, identification of the most
      suitable approach tends to become more and more challenging as the number of
      therapeutic alternatives continues to increase due to medical innovation. In this
      study, the challenge of decision making in modern dentistry is illustrated using
      the example of bounded edentulous spaces. Many therapeutic alternatives exist for
      such clinical scenarios, including a noninvasive monitoring approach, minimally
      invasive tooth recontouring, orthodontic and prosthodontic treatment, and implant
      placement. The findings of this pilot study highlight the utmost relevance of
      incorporating individual patients' needs and risks into clinical treatment
      planning and providing appropriate guidelines.

PMID- 27689933
TI  - Improved In Vivo Stability of Radioiodinated Rituximab Using an Iodination Linker
      for Radioimmunotherapy.
AB  - PURPOSE: Directly radioiodinated [131I]-rituximab has been developed as a
      radioimmunotherapeutic agent in patients with CD20-positive B cell non-Hodgkin's
      lymphoma. However, there are concerns over its in vivo catabolism and
      deiodination. A novel radioiodination linker, N-(4-isothiocyanatobenzyl)-2-(3
      (tributylstannyl)phenyl) acetamide (IBPA), was synthesized for the preparation of
      stable radioiodinated proteins. METHODS: The authors evaluated the potential of
      IBPA as a stable radioiodinated linker for rituximab. [125I]-IBPA was purified
      and conjugated with rituximab, and in vitro stability testing was performed in
      serum and liver microsomes. In vivo studies were performed after i.v. injection
      of [125I]-rituximab or [125I]-IBPA-rituximab to nude mice. RESULTS: In in vitro
      studies, [125I]-IBPA-rituximab was stable in serum and liver microsomes. In
      static scans, high radioactivity was evident in the thyroid following injection
      of [125I]-rituximab, but low radioactivity was seen in the thyroid following
      injection of [125I]-IBPA-rituximab. In biodistribution studies, radioactivity
      uptake in thyroid glands of [125I]-IBPA-rituximab was decreased by approximately
      sevenfold compared to [125I]-rituximab. In pharmacokinetics, the half-life of
      [125I]-rituximab was shorter than that of [125I]-IBPA-rituximab in plasma of nude
      mice. CONCLUSIONS: The authors demonstrate that [125I]-IBPA-rituximab is more
      stable to metabolic deiodination in vivo than is [125I]-rituximab.
      Radioiodination of rituximab using IBPA is thus preferable to direct labeling in
      terms of in vivo stability.

PMID- 27689934
TI  - Epigenetic Signatures at the RUNX2-P1 and Sp7 Gene Promoters Control Osteogenic
      Lineage Commitment of Umbilical Cord-Derived Mesenchymal Stem Cells.
AB  - Wharton's Jelly mesenchymal stem cells (WJ-MSCs) are an attractive potential
      source of multipotent stem cells for bone tissue replacement therapies. However,
      the molecular mechanisms involved in their osteogenic conversion are poorly
      understood. Particularly, epigenetic control operating at the promoter regions of
      the two master regulators of the osteogenic program, RUNX2/P57 and SP7 has not
      yet been described in WJ-MSCs. Via quantitative PCR profiling and chromatin
      immunoprecipitation (ChIP) studies, here we analyze the ability of WJ-MSCs to
      engage osteoblast lineage. In undifferentiated WJ-MSCs, RUNX2/P57 P1, and SP7
      promoters are found deprived of significant levels of the histone post
      translational marks that are normally associated with transcriptionally active
      genes (H3ac, H3K27ac, and H3K4me3). Moreover, the RUNX2 P1 promoter lacks two
      relevant histone repressive marks (H3K9me3 and H3K27me3). Importantly, RUNX2 P1
      promoter is found highly enriched in the H3K4me1 mark, which has been shown
      recently to mediate gene repression of key regulatory genes. Upon induction of WJ
      MSCs osteogenic differentiation, we found that RUNX2/P57, but not SP7 gene
      expression is strongly activated, in a process that is accompanied by enrichment
      of activating histone marks (H3K4me3, H3ac, and H3K27ac) at the P1 promoter
      region. Histone mark analysis showed that SP7 gene promoter is robustly enriched
      in epigenetic repressive marks that may explain its poor transcriptional response
      to osteoblast differentiating media. Together, these results point to critical
      regulatory steps during epigenetic control of WJ-MSCs osteogenic lineage
      commitment that are relevant for future applications in regenerative medicine. J.
      Cell. Physiol. 232: 2519-2527, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27689937
TI  - Calibration bias of experimentally determined chlorine isotope enrichment
      factors: the need for a two-point calibration in compound-specific chlorine
      isotope analysis.
AB  - RATIONALE: The recent development of compound-specific online chlorine isotope
      analysis (37 Cl-CSIA) methods has fostered dual chlorine-carbon isotope studies
      to gain better insights into sources and environmental transformation reactions
      of chlorinated ethenes. One-point and two-point calibration schemes are currently
      used to convert raw data to the international delta37 ClSMOC scale, but a
      critical evaluation of best practices to arrive at reliable delta37 ClSMOC
      signatures and enrichment factors was missing and is presented here. METHODS:
      Aqueous solutions of neat perchloroethylene and trichloroethylene (TCE) and
      aqueous samples from a TCE biodegradation experiment with pure cultures of
      Desulfitobacterium hafniense Y51 were analysed for their chlorine isotope ratios
      using GC/qMS and GC/IRMS. The delta37 ClSMOC values were obtained using one-point
      and two-point calibration schemes. Chlorine isotope enrichment factors, epsilonCl
      , were calculated using both approaches and the corresponding bias of delta37
      ClSMOC values introduced by the different types of calibration was determined.
      RESULTS: Different calibration methods resulted in significant differences (up to
      30%) in both delta37 Cl signatures and epsilonCl values. CONCLUSIONS: Our results
      demonstrate that a two-point calibration together with comprehensive information
      on reference materials is indispensable and should become standard practice for
      reliable 37 Cl-CSIA of organic compounds. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 27689936
TI  - Local Mechanical Perturbation Provides an Effective Means to Regulate the Growth
      and Assembly of Functional Peptide Fibrils.
AB  - Mucin 1 (MUC1) peptide fused with Q11 (MUC1-Q11) having 35 residues has
      previously been shown to form amyloid fibrils. Using time-dependent and high
      resolution atomic force microscopy (AFM) imaging, it is revealed that the
      formation of individual MUC1-Q11 fibrils entails nucleation and extension at both
      ends. This process can be altered by local mechanical perturbations using AFM
      probes. This work reports two specific perturbations and outcomes. First, by
      increasing load while maintaining tip-surface contact, the fibrils are cut during
      the scan due to shearing. Growth of fibrils occurs at the newly exposed termini,
      following similar mechanism of the MUC1-Q11 nucleation growth. As a result,
      branched fibrils are seen on the surface whose orientation and length can be
      controlled by the nuclei orientation and reaction time. In contrast to the "one
      time-cut", fibrils can be continuously fragmented by modulation at sufficiently
      high amplitude. As a result, short and highly branched fibrils accumulate and
      pile on surfaces. Since the fibril formation and assembly of MUC1-Q11 can be
      impacted by local mechanical force, this approach offers a nonchemical and label
      free means to control the presentation of MUC1 epitopes, and has promising
      application in MUC1 fibril-based immunotherapy.

PMID- 27689935
TI  - Coordination-Driven Self-Assembly and Anticancer Potency Studies of Ruthenium
      Cobalt-Based Heterometallic Rectangles.
AB  - Three new cobalt-ruthenium heterometallic molecular rectangles, 1-3, were
      synthesized through the coordination-driven self-assembly of a new cobalt
      sandwich donor, (eta5 -Cp)Co[C4 -trans-Ph2 (4-Py)2 ] (L; Cp: cyclopentyl; Py:
      pyridine), and one of three dinuclear precursors, [(p-cymene)2 Ru2 (OO?OO)2 Cl2 ]
      [OO?OO: oxalato (A1 ), 5,8-dioxido-1,4-naphthoquinone (A2 ), or 6,11-dioxido-5,12
      naphthacenedione (A3 )]. All of the self-assembled architectures were isolated in
      very good yield (92-94 %) and were fully characterized by spectroscopic analysis;
      the molecular structures of 2 and 3 were determined by single-crystal X-ray
      diffraction analysis. The anticancer activities of bimetallic rectangles 1-3 were
      evaluated with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
      (MTT) assay, an autophagy assay, and Western blotting. Rectangles 1-3 showed
      higher cytotoxicity than doxorubicin in AGS human gastric carcinoma cells. In
      addition, the autophagic activities and apoptotic cell death ratios were
      increased in AGS cells by treatment with 1-3; the rectangles induced
      autophagosome formation by promoting LC3-I to LC3-II conversion and apoptotic
      cell death by increasing caspase-3/7 activity. Our results suggest that
      rectangles 1-3 induce gastric cancer cell death by modulating autophagy and
      apoptosis and that they have potential use as agents for the treatment of human
      gastric cancer.

PMID- 27689938
TI  - NMR Diffusion Measurements as a Simple Method to Examine Solvent-Solvent and
      Solvent-Solute Interactions in Mixtures of the Ionic Liquid [Bmim][N(SO2 CF3 )2 ]
      and Acetonitrile.
AB  - The self-diffusion coefficients of each component in mixtures of 1-butyl-3
      methylimidazolium bis(trifluoromethanesulfonyl)imide ([Bmim][N(SO2 CF3 )2 ]) and
      acetonitrile were determined. The results suggest that the hydrodynamic boundary
      conditions change from "stick" to "slip" as the solvent composition transitions
      from "ionic liquid dissolved in acetonitrile" (chiIL <0.4) to "acetonitrile
      dissolved in ionic liquid" (chiIL >0.4). At higher chiIL , the acetonitrile
      species are affected by "cage" and "jump" events, as the acetonitrile molecules
      reside nearer to the charged centre on the ions than in the "non-polar" regions.
      The self-diffusion coefficients of hexan-1-amine, dipropylamine, 1-hexanol and
      dipropylether in mixtures of [Bmim][N(SO2 CF3 )2 ] and acetonitrile were
      determined. In general, the nitrogen-containing solutes were found to diffuse
      slower than the oxygen-containing solutes; this indicates that there are greater
      ionic liquid-N interactions than ionic liquid-O interactions. This work
      demonstrates that the self-diffusion coefficients of species can provide valuable
      information about solvent-solvent and solvent-solute interactions in mixtures
      containing an ionic liquid.

PMID- 27689939
TI  - Three-dimensional direct cell bioprinting for tissue engineering.
AB  - Bioprinting is a relatively new technology where living cells with or without
      biomaterials are printed layer-by-layer in order to create three-dimensional (3D)
      living structures. In this article, novel bioprinting methodologies are developed
      to fabricate 3D biological structures directly from computer models using live
      multicellular aggregates. Multicellular aggregates made out of at least two cell
      types from fibroblast, endothelial and smooth muscle cells are prepared and
      optimized. A novel bioprinting approach is proposed in order to continuously
      extrude cylindrical multicellular aggregates through the bioprinter's glass
      microcapillaries. The multicellular aggregates are first aspirated into a
      capillary and then compressed to form a continuous cylindrical multicellular
      bioink. To overcome surface tension-driven droplet formation, the required
      compression ratio is calculated. Based on the developed bioprinting strategies,
      multicellular aggregates and their support structures are bioprinted to form 3D
      tissue constructs with predefined shapes. The effect of the bioprinting process
      was examined for fusion, cell viability at different compression ratios, and f
      actin cytoskeletal organization. The results show that the bioprinted 3D
      constructs fuse rapidly and have high cell viability after printing. (c) 2016
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2530
      2544, 2017.

PMID- 27689940
TI  - Metal-Phenolic Supramolecular Gelation.
AB  - Materials assembled by coordination interactions between naturally abundant
      polyphenols and metals are of interest for a wide range of applications,
      including crystallization, catalysis, and drug delivery. Such an interest has led
      to the development of thin films with tunable, dynamic properties, however,
      creating bulk materials remains a challenge. Reported here is a class of
      metallogels formed by direct gelation between inexpensive, naturally abundant
      tannic acid and group(IV) metal ions. The metallogels exhibit diverse properties,
      including self-healing and transparency, and can be doped with various materials
      by in situ co-gelation. The robustness and flexibility, combined with the ease,
      low cost, and scalability of the coordination-driven assembly process make these
      metallogels potential candidates for chemical, biomedical, and environmental
      applications.

PMID- 27689941
TI  - Taming Liquid Crystal Self-Assembly: The Multifaceted Response of Nematic and
      Smectic Shells to Polymerization.
AB  - By photopolymerizing liquid crystal shells, their rich variety of self-assembled
      structures can be rendered permanent and the lifetime extended from days to
      months, without removing the characteristic responsiveness. If polymerization is
      carried out close to either boundary of the nematic phase, the process triggers
      the transition into the adjacent phase, to higher or to lower degree of order.

PMID- 27689942
TI  - Bioactive coating of decellularized vascular grafts with a temperature-sensitive
      VEGF-conjugated hydrogel accelerates autologous endothelialization in vivo.
AB  - No ideal small-diameter vascular graft for widespread clinical application has
      yet been developed and current approaches still suffer from graft failure because
      of thrombosis or degeneration. Decellularized vascular grafts are a promising
      strategy as they preserve native vessel architecture while eliminating cell-based
      antigens and allow for autologous recellularization. In the present study, a
      functional in vivo rodent aortic transplantation model was used in order to
      evaluate the benefit of bioactive coating of decellularized vascular grafts with
      vascular endothelial growth factor (VEGF) conjugated to a temperature-sensitive
      aliphatic polyester hydrogel (HG). Luminal HG-VEGF coating persistence up to 4
      weeks was confirmed in vivo by rhodamine-labelling. Doppler-sonography showed
      that the grafts were functional for up to 8 weeks in vivo. Histological and
      immunohistochemical analysis of the explanted grafts after 4 weeks and 8 weeks in
      vivo demonstrated significantly increased endothelium formation in the HG-VEGF
      group compared with the control group (luminal surface covered with single
      layered endothelium, 4 weeks: 64.8 +/- 7.6% vs. 40.4 +/- 8.3%, p = 0.025) as well
      as enhanced media recellularization (absolute cell count, 8 weeks: 22.1 +/- 13.0
      vs. 3.2 +/- 3.6, p = 0.0039). However, HG-VEGF coating also led to increased neo
      intimal hyperplasia, resulting in a significantly increased intima-to-media ratio
      in the perianastomotic regions (intima-to-media ratio, 8 weeks: 1.61 +/- 0.17 vs.
      0.93 +/- 0.09, p = 0.008; HG-VEGF vs. control). The findings indicate that HG
      VEGF coating has potential for the development of engineered small-diameter
      artificial grafts, although further research is needed to prevent neo-intimal
      hyperplasia. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27689943
TI  - High fear of intra-oral injections: prevalence and relationship to dental fear
      and dental avoidance among 10- to 16-yr-old children.
AB  - The present study aimed to: (i) estimate the prevalence of self-reported high
      fear of intra-oral injections, high blood-injury fear, and injection fear; (ii)
      explore the overlap between high fear of intra-oral injections and high fear of
      dental treatment; and (iii) evaluate the possible consequence of high fear of
      intra-oral injections in terms of avoidance of dental care. The sample included
      1,441 subjects, 10- to 16-yr of age, attending elementary schools in a county of
      Norway. Data were collected using questionnaires that were completed in
      classrooms. The survey instruments used were the Intra-Oral Injection Fear-scale,
      the Children's Fear Survey Schedule-Dental Subscale, the Injection Phobia scale
      for children, and the Mutilation Questionnaire for children. In total, 13.9% of
      the children reported high intra-oral injection fear. A strong association was
      found between fear of intra-oral injections and dental fear. When an intra-oral
      injection was needed, 10.6% would avoid dental treatment. In multiple regression
      analysis, high intra-oral injection fear was found to be associated with
      avoidance of dental treatment (OR = 6.52; 95% CI: 3.99-10.67). It was concluded
      that high fear of intra-oral injections was prevalent and might lead to avoidance
      of necessary dental treatment. Hence, intra-oral injection fear should be
      addressed before treatment of dental fear.

PMID- 27689944
TI  - Metabolic health profile in young adults with Prader-Willi syndrome: results of a
      2-year randomized, placebo-controlled, crossover GH trial.
AB  - CONTEXT: Patients with Prader-Willi syndrome (PWS) have an increased fat mass and
      decreased lean body mass. GH-treated young adults with PWS who have attained
      adult height benefit from continuation of growth hormone (GH) treatment, as GH
      maintained their improved body composition, whereas fat mass increased during the
      placebo period. Adults with PWS are predisposed to T2DM and cardiovascular
      disease. Whether GH affects metabolic health profile of this patient group is
      unknown. OBJECTIVE: To investigate the effects of GH vs placebo on metabolic
      health, in young adults with PWS who were GH-treated for many years during
      childhood and had attained adult height (AH). METHOD: A 2-year, randomized,
      double-blind, placebo-controlled crossover study with stratification for gender
      and BMI in 27 young adults with PWS. Intervention with GH (0.67 mg/m2 /day) and
      placebo, both for 1-year duration. RESULTS: Compared to placebo, GH treatment
      resulted in similar glucose and insulin levels during oral glucose tolerance
      test. Only fasting glucose and insulin were slightly higher during GH vs placebo
      (+0.2 mmol/l and +18.4 pmol/l), although both remained within normal ranges in
      both phases. Blood pressure and lipid profile were similar after GH vs placebo.
      At baseline (AH) and during GH, no patients had metabolic syndrome, while 1
      developed it during placebo treatment. CONCLUSIONS: Growth hormone treatment has
      no adverse effects on metabolic health profile. Thus, GH-treated young adults
      with PWS who have attained AH benefit from continuation of GH treatment without
      safety concerns regarding metabolic health.

PMID- 27689945
TI  - Effect of Active Videogames on Underserved Children's Classroom Behaviors,
      Effort, and Fitness.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of active
      videogames (AVGs) on underserved minority children's on-task classroom behavior,
      academic effort, and fitness. MATERIALS AND METHODS: A one group pre- and
      posttest repeated measures design was used. In Fall 2013, 95 fourth grade
      children (57 boys, 38 girls; 96% of minority) from three classes at an
      underserved urban elementary school participated in teacher-supervised AVG
      activities (e.g., Wii Sports, Xbox Just Dance). Specifically, students
      participated in a 50-minute weekly AVG program at school for 6 weeks. Children's
      academic effort was evaluated by classroom teachers using a validated scale that
      assessed activity, attention, conduct, and social/emotional behavior. Moreover,
      children's classroom behavior was observed immediately before and after each AVG
      session by trained researchers. Finally, cardiovascular fitness was also
      measured. RESULTS: A paired t-test was used to assess teacher-rated student
      effort, while one-way (gender) analysis of variance (ANOVA) with repeated
      measures was performed to analyze children's on-task classroom behavior. There
      was a significant effect on children's effort between the first (mean = 3.24, SD
      = 0.75) and last week (mean = 3.41, SD = 0.73) assessments, t = 2.42, P = 0.02.
      In addition, there was a significant effect on classroom behavior, F = 33.103, P
      < 0.01. In detail, children scored significantly higher on on-task behavior
      during the post-AVG observation (mean = 81.4, SD = 12.3) than seen during the pre
      AVG observation (mean = 69.8, SD = 14.9). However, no main effect was indicated
      for gender, F = 0.39, P = 0.54. No significant improvement in cardiovascular
      fitness was observed, although slight improvements were seen. CONCLUSION:
      Offering an AVG program at school could improve underserved minority children's
      classroom on-task behavior and academic effort. Future studies may include a
      control group to further confirm the effectiveness of AVG activities. Practical
      implications for educators and other stakeholders are provided.

PMID- 27689946
TI  - Expectations of Graduate Communication Skills in Professional Veterinary
      Practice.
AB  - Good communication skills are an important entry-level attribute of graduates of
      professional degrees. The inclusion of communication training within the
      curriculum can be problematic, particularly in programs with a high content load,
      such as veterinary science. This study examined the differences between the
      perceptions of students and qualified veterinarians with regards to the entry
      level communication skills required of new graduates in clinical practice.
      Surveys were distributed to students in each of the four year levels of the
      veterinary science degree at the University of Melbourne and to recent graduates
      and experienced veterinarians registered in Victoria, Australia. Respondents were
      asked to rank the relative importance of six different skill sets: knowledge
      base; medical and technical skills; surgical skills; verbal communication and
      interpersonal skills; written communication skills; and critical thinking and
      problem solving. They were then asked to rate the importance of specific
      communication skills for new graduate veterinarians. Veterinarians and students
      ranked verbal communication and interpersonal skills as the most important skill
      set for an entry-level veterinarian. Veterinarians considered many new graduates
      to be deficient in these skills. Students often felt they lacked confidence in
      this area. This has important implications for veterinary educators in terms of
      managing the expectations of students and improving the delivery of communication
      skills courses within the veterinary curriculum.

PMID- 27689947
TI  - Patients Without Borders: Using Telehealth to Provide an International Experience
      in Veterinary Global Health for Veterinary Students.
AB  - There is an increasing need to produce veterinarians with knowledge and critical
      thinking skills that will allow them to participate in veterinary global health
      equity delivery, particularly in the developing world, where many people remain
      dependent on animal-based agriculture for a living. This need for veterinarians
      trained in global health is reflected by the demand among students for greater
      exposure and education. At the same time, many students are held back from on
      site training in global health due to constraints of cost, time, or family
      obligations. The purpose of this article is to describe the use of a telemedicine
      approach to educating veterinary students at Tufts Cummings School of Veterinary
      Medicine. This approach simultaneously provides expert consultation and support
      for a pro bono hospital in the developing world. The development of a
      telemedicine teaching service is discussed, from initial ad hoc email
      consultation among friends and associates to a more formal use of store-and
      forward delivery of data along with real-time videoconferencing on a regular
      basis, termed tele-rounds. The practicalities of data delivery and exchange and
      best use of available bandwidth are also discussed, as this very mundane
      information is critical to efficient and useful tele-rounds. Students are able to
      participate in discussion of cases that they would never see in their usual
      clinical sphere and to become familiar with diagnostic and treatment approaches
      to these cases. By having the patient "virtually" brought to us, tele-rounds also
      decrease the usual carbon footprint of global health delivery.

PMID- 27689948
TI  - Professional Veterinary Programs' Perceptions and Experiences Pertaining to
      Emotional Support Animals and Service Animals, and Recommendations for Policy
      Development.
AB  - Given the unique nature of programs in professional veterinary medicine (PVM),
      the increasing numbers of students requesting accommodations for emotional
      support animals (ESAs) in higher education settings is of growing interest to
      student affairs and administrative staff in PVM settings. Since the legislation
      pertaining to this type of support animal differs from the laws governing
      disability service animals, colleges and universities now need to develop new
      policies and guidelines. Representatives from a sample of 28 PVM programs
      completed a survey about the prevalence of student requests for ESAs and service
      animals. PVM associate deans for academic affairs also reported their perceptions
      of this issue and the challenges these requests might pose within veterinary
      teaching laboratories and patient treatment areas. Responses indicated that
      approximately one third of PVM programs have received requests for ESAs (32.1%)
      in the last 2 years, 17.9% have had requests for psychiatric service animals, and
      17.9% for other types of service animals. Despite this, most associate deans
      reported not having or not being aware of university or college policies
      pertaining to these issues. Most associate deans are interested in learning more
      about this topic. This paper provides general recommendations for establishing
      university or PVM program policies.

PMID- 27689951
TI  - Diagnosis of Cutaneous T-Cell Lymphoma Detecting T-Cell Receptor gamma Chain Gene
      Monoclonality By Denaturing Gradient Gel Electrophoresis.
AB  - Cutaneous T-cell lymphomas represent a group of malignant lymphoproliferative
      disorders characterised by the occurrence of a monoclonal population of T
      lymphocytes. Diagnosis of early stages of this disease is a difficult challenge
      for both the dermatologist and the dermatopathologist. With the aid of the
      polymerase chain reaction it is possible to amplify specific regions of the T
      cell receptor gamma gene. The amplification products can then be separated by
      denaturing gradient gel electrophoresis in order to detect a monoclonal
      population of T-lymphocytes in the infiltrate. We studied 4 patients with the
      clinicopathologic diagnosis of mycosis fungoides and 2 patients diagnosed as
      large plaque parapsoriasis. A monoclonal population was detected in 3 of the 4
      mycosis fungoides cases and in 1 of the patients with large plaque parapsoriasis.
      This indicates that our analysis can help us establishing a diagnosis, and it can
      also help us to identify patients with a possible early stage of the disease,
      which clinically or histologically is not yet recognised as such.

PMID- 27689949
TI  - Robust factor selection in early cell culture process development for the
      production of a biosimilar monoclonal antibody.
AB  - This work presents a multivariate methodology combining principal component
      analysis, the Mahalanobis distance and decision trees for the selection of
      process factors and their levels in early process development of generic
      molecules. It is applied to a high throughput study testing more than 200
      conditions for the production of a biosimilar monoclonal antibody at microliter
      scale. The methodology provides the most important selection criteria for the
      process design in order to improve product quality towards the quality attributes
      of the originator molecule. Robustness of the selections is ensured by cross
      validation of each analysis step. The concluded selections are then successfully
      validated with an external data set. Finally, the results are compared to those
      obtained with a widely used software revealing similarities and clear advantages
      of the presented methodology. (c) 2016 American Institute of Chemical Engineers
      Biotechnol. Prog., 33:181-191, 2017.

PMID- 27689952
TI  - Belgian Consensus Recommendations for Flow Cytometric Immunophenotyping.
AB  - This paper summarises the guidelines and recommendations that were generated
      during a number of discussion forums attended by the majority of Belgian
      cytometry laboratory professionals. These forums focused on the rational and
      optimal use of flow cytometric evaluations in the clinical laboratory setting.
      The aim was to improve the coherence of the testing panels and the quality of the
      results and -as such-the clinical diagnostic information. It was also the aim to
      provide the Belgian prescribing physician and interested laymen with an updated
      overview of the flow cytometric possibilities. Emphasis is placed on
      immunophenotyping of haematological malignancies, hematopoietic progenitor cell
      counting and follow-up of the viral infection caused by the human
      immunodeficiency virus.

PMID- 27689953
TI  - Belgian Association for the Study of Cancer.

PMID- 27689955
TI  - The dynamic factors in regeneration. First published in 1909 in The Biological
      Bulletin, Vol. 16: 265-276.
AB  - With the publication of the data here presented the series of experiments that I
      have carried out on Tubularia for several years may be considered as temporarily
      brought to a close. I take this opportunity therefore to sum up the evidence
      bearing on the problem of the formative factors of regeneration, as exhibited by
      this hydroid. In the course of my experiments tentative hypotheses have been
      proposed here and there that have at least served to suggest further experiments.
      The conflicting evidence sometimes inclined me towards one point of view,
      sometimes towards another; yet, all in all, the same general line of thought, if
      sometimes vague, can be traced through the attempts to analyze the results. It
      will be my endeavor here to bring more into the foreground those theoretical
      deductions that seem to me at present to be best in harmony with the experimental
      evidence...

PMID- 27689956
TI  - Risk Factors for All-Cause Rehospitalization Among Medicare Recipients with Heart
      Failure Receiving Telehomecare.
AB  - OBJECTIVE: To identify potential risk factors associated with rehospitalization
      among Medicare recipients with heart failure (HF) receiving telehomecare.
      MATERIALS AND METHODS: This study is a nonexperimental, cross-sectional secondary
      data analysis of the Centers for Medicare and Medicaid (CMS) mandated assessment
      called the Outcome and Assessment Information Set (OASIS)-C, provided by a large
      home care company. A total of 526 patients who received telehomecare from January
      1, 2011 to August 31, 2013 were included in the analyses, which used multiple
      logistic regression. RESULTS: The overall rate of rehospitalization was 36% while
      patients were receiving telehomecare. Moderately frail health status (p = 0.01),
      the presence of severe pain (p = 0.01), the presence of dermatologic problems (p
      = 0.03), and independence in dressing one's lower body (compared to slightly
      dependent [p = 0.01] or mostly dependent patient groups [p = 0.02]) were
      identified as risk factors for rehospitalization. CONCLUSIONS: The risk factors
      identified from this study may be used to drive more effective telehomecare
      placements, and referrals for additional services among telehomecare patients
      with HF.

PMID- 27689957
TI  - Anti-calreticulin antibodies and calreticulin in sera of patients diagnosed with
      dilated or hypertrophic cardiomyopathy.
AB  - Distinct cellular level of the Ca2+-binding chaperone calreticulin (CRT) is
      essential for correct embryonal cardiac development and postnatal function.
      However, CRT is also a potential autoantigen eliciting formation of antibodies
      (Ab), whose role is not yet clarified. Immunization with CRT leads to cardiac
      injury, while overexpression of CRT in cardiomyocytes induces dilated
      cardiomyopathy (DCM) in animals. Hence, we analysed levels of anti-CRT Ab and
      calreticulin in the sera of patients with idiopatic DCM and hypertrophic
      cardiomyopathy (HCM). ELISA and immunoblot using human recombinant CRT and
      Pepscan with synthetic, overlapping decapeptides of CRT were used to detect anti
      CRT Ab. Serum CRT concentration was tested by ELISA. Significantly increased
      levels of anti-CRT Ab of isotypes IgA (p < 0.001) and IgG (p < 0.05) were found
      in patients with both DCM (12/34 seropositive for IgA, 7/34 for IgG) and HCM
      (13/38 seropositive for IgA, 11/38 for IgG) against healthy controls (2/79 for
      IgA, 1/79 for IgG). Titration analysis in seropositive DCM and HCM patients
      documented anti-CRT Ab detected at 1/1600 dilution for IgG and 1/800 for IgA (and
      IgA1) and at least at 1/200 dilution for IgA2, IgG1, IgG2 and IgG3. Pepscan
      identified immunogenic CRT epitopes recognized by IgA and IgG Ab of these
      patients. Significantly increased levels of CRT relative to healthy controls were
      found in sera of patients with HCM (p < 0.01, 5/19). These data extend the
      knowledge of seroprevalence of anti-CRT Ab and CRT, and suggest possible
      involvement of autoimmune mechanisms directed to CRT in some forms of
      cardiomyopathies, which are clinically heterogeneous.

PMID- 27689959
TI  - Tell all the good news as soon as possible.

PMID- 27689958
TI  - Barriers to Translation of Physical Activity into the Lung Cancer Model of Care.
      A Qualitative Study of Clinicians' Perspectives.
AB  - RATIONALE: Evidence-based clinical practice guidelines recommend physical
      activity for people with lung cancer, however evidence has not translated into
      clinical practice and the majority of patients do not meet recommended activity
      levels. OBJECTIVES: To identify factors (barriers and enablers) that influence
      clinicians' translation of the physical activity guidelines into practice.
      METHODS: Qualitative study involving 17 participants (three respiratory
      physicians, two thoracic surgeons, two oncologists, two nurses, and eight
      physical therapists) who were recruited using purposive sampling from five
      hospitals in Melbourne, Victoria, Australia. Nine semistructured interviews and a
      focus group were conducted, transcribed verbatim, and independently cross-checked
      by a second researcher. Thematic analysis was used to analyze data. MEASUREMENTS
      AND MAIN RESULTS: Five consistent themes emerged: (1) the clinicians perception
      of patient-related physical and psychological influences (including symptoms and
      comorbidities) that impact on patient's ability to perform regular physical
      activity; (2) the influence of the patient's past physical activity behavior and
      their perceived relevance and knowledge about physical activity; (3) the
      clinicians own knowledge and beliefs about physical activity; (4) workplace
      culture supporting or hindering physical activity; and (5) environmental and
      structural influences in the healthcare system (included clinicians time,
      staffing, protocols and services). Clinicians described potential strategies,
      including: (1) the opportunity for nurse practitioners to act as champions of
      regular physical activity and triage referrals for physical activity services;
      (2) opportunistically using the time when patients are in hospital after surgery
      to discuss physical activity; and (3) for all members of the multidisciplinary
      team to provide consistent messages to patients about the importance of physical
      activity. CONCLUSIONS: Key barriers to implementation of the physical activity
      guidelines in lung cancer are diverse and include both clinician- and healthcare
      system-related factors. A combined approach to target a number of these factors
      should be used to inform research, improve clinical services, and develop
      policies aiming to increase physical activity and improve survivorship outcomes
      for patients with lung cancer.

PMID- 27689960
TI  - Corrigendum.

PMID- 27689961
TI  - Highly enhanced compatibility of human brain vascular pericyte cells on monolayer
      graphene.
AB  - We introduce a method for increasing the compatibility of human brain vascular
      pericyte (HBVP) cells on a glass substrate, based on wet transferred monolayer
      graphene without any treatment. As a novel material, graphene has key properties
      for incubating cells, such as chemical stability, transparency, appropriate
      roughness, hydrophobicity and high electrical conductivity. These outstanding
      properties of graphene were examined by Raman spectroscopy, water contact angle
      measurements and atomic force microscopy. The performance of this graphene-based
      implant was investigated by a cell compatibility test, comparing the growth rate
      of cells on the graphene surface and that on a bare glass substrate. After an
      incubation period of 72 h, the number of live HBVP cells on a graphene surface
      with an area of 1*1 mm2 was 1.83 times greater than that on the glass substrate.

PMID- 27689962
TI  - Can photoreceptor loss also account for changes in pupil size following
      panretinal photocoagulation?

PMID- 27689963
TI  - Multicolor imaging in the diagnosis and follow up of type 2 acute macular
      neuroretinopathy.
AB  - PurposeTo study the usefulness of multicolor imaging (MC) photographs in addition
      to near infrared reflectance (NIR) and spectral domain optical coherence
      tomography (SD-OCT) in the detection and follow up of acute macular
      neuroretinopathy (AMN).Patients and methodsSix patients with a complaint of
      paracentral scotomas in at least one eye due to AMN were included. They underwent
      full ophthalmic examination and multimodal imaging including color fundus
      photographs, (SD-OCT), NIR, and MC at baseline and follow up.ResultsFour females
      and two males, aged 19-64 years, and eight eyes affected by AMN, were included.
      Acute phase SD-OCT in all patients confirmed the diagnosis of type 2 AMN with
      partial recovery of the outer retina in the convalescent phase. NIR and MC
      elicited in all cases hypo-reflective AMN lesions pointing toward the fovea. MC
      exhibited a higher contrast between the affected and the physiologic retina that
      slowly attenuated during the follow up showing a decrease in the hypo-reflectance
      of the lesions.ConclusionMC imaging was more detailed than fundus color
      photographs and as detailed as NIR in the detection of AMN. When available, MC
      imaging should complement SD-OCT and NIR in the diagnosis and follow up of this
      rare inflammatory condition that may be underdiagnosed.

PMID- 27689965
TI  - Maxillary distraction osteogenesis versus orthognathic surgery for cleft lip and
      palate patients.
AB  - BACKGROUND: Cleft lip and palate is one of the most common birth defects and can
      cause difficulties with feeding, speech and hearing, as well as psychosocial
      problems. Treatment of orofacial clefts is prolonged; it typically commences
      after birth and lasts until the child reaches adulthood or even into adulthood.
      Residual deformities, functional disturbances, or both, are frequently seen in
      adults with a repaired cleft. Conventional orthognathic surgery, such as Le Fort
      I osteotomy, is often performed for the correction of maxillary hypoplasia. An
      alternative intervention is distraction osteogenesis, which achieves bone
      lengthening by gradual mechanical distraction. OBJECTIVES: To provide evidence
      regarding the effects and long-term results of maxillary distraction osteogenesis
      compared to orthognathic surgery for the treatment of hypoplastic maxilla in
      people with cleft lip and palate. SEARCH METHODS: We searched the following
      electronic databases: Cochrane Oral Health's Trials Register (to 16 February
      2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane
      Library, 2016, Issue 1), MEDLINE Ovid (1946 to 16 February 2016), Embase Ovid
      (1980 to 16 February 2016), LILACS BIREME (1982 to 16 February 2016), the US
      National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) (to 16
      February 2016), and the World Health Organization (WHO) International Clinical
      Trials Registry Platform (to 16 February 2016). There were no restrictions
      regarding language or date of publication in the electronic searches. We
      performed handsearching of six speciality journals and we checked the reference
      lists of all trials identified for further studies. SELECTION CRITERIA: We
      included randomised controlled trials (RCTs) comparing maxillary distraction
      osteogenesis to conventional Le Fort I osteotomy for the correction of cleft lip
      and palate maxillary hypoplasia in non-syndromic cleft patients aged 15 years or
      older. DATA COLLECTION AND ANALYSIS: Two review authors assessed studies for
      eligibility. Two review authors independently extracted data and assessed the
      risk of bias in the included studies. We contacted trial authors for
      clarification or missing information whenever possible. All standard
      methodological procedures expected by Cochrane were used. MAIN RESULTS: We found
      six publications involving a total of 47 participants requiring maxillary
      advancement of 4 mm to 10 mm. All of them related to a single trial performed
      between 2002 and 2008 at the University of Hong Kong, but not all of the
      publications reported outcomes from all 47 participants. The study compared
      maxillary distraction osteogenesis with orthognathic surgery, and included
      participants from 13 to 45 years of age.Results and conclusions should be
      interpreted with caution given the fact that this was a single trial at high risk
      of bias, with a small sample size.The main outcomes assessed were hard and soft
      tissue changes, skeletal relapse, effects on speech and velopharyngeal function,
      psychological status, and clinical morbidities.Both interventions produced
      notable hard and soft tissue improvements. Nevertheless, the distraction group
      demonstrated a greater maxillary advancement, evaluated as the advancement of
      Subspinale A-point: a mean difference of 4.40 mm (95% CI 0.24 to 8.56) was
      recorded two years postoperatively.Horizontal relapse of the maxilla was
      significantly less in the distraction osteogenesis group five years after
      surgery. A total forward movement of A-point of 2.27 mm was noted for the
      distraction group, whereas a backward movement of 2.53 mm was recorded for the
      osteotomy group (mean difference 4.8 mm, 95% CI 0.41 to 9.19).No statistically
      significant differences could be detected between the groups in speech outcomes,
      when evaluated through resonance (hypernasality) at 17 months postoperatively (RR
      0.11, 95% CI 0.01 to 1.85) and nasal emissions at 17 months postoperatively (RR
      3.00, 95% CI 0.14 to 66.53), or in velopharyngeal function at the same time point
      (RR 1.28, 95% CI 0.65 to 2.52).Maxillary distraction initially lowered social
      self-esteem at least until the distractors were removed, at three months
      postoperatively, compared to the osteotomy group, but this improved over time and
      the distraction group had higher satisfaction with life in the long term (two
      years after surgery) (MD 2.95, 95% CI 014 to 5.76).Adverse effects, in terms of
      clinical morbidities, included mainly occlusal relapse and mucosal infection,
      with the frequency being similar between groups (3/15 participants in the
      distraction osteogenesis group and 3/14 participants in the osteotomy group).
      There was no severe harm to any participant. AUTHORS' CONCLUSIONS: This review
      found only one small randomised controlled trial concerning the effectiveness of
      distraction osteogenesis compared to conventional orthognathic surgery. The
      available evidence is of very low quality, which indicates that further research
      is likely to change the estimate of the effect. Based on measured outcomes,
      distraction osteogenesis may produce more satisfactory results; however, further
      prospective research comprising assessment of a larger sample size with
      participants with different facial characteristics is required to confirm
      possible true differences between interventions.

PMID- 27689964
TI  - Subfoveal choroidal thickness as a predictor of central serous chorioretinopathy.
AB  - PurposeThe purpose of the study was to evaluate the role of subfoveal choroidal
      thickness (CT) measurements as a predictor for the course of central serous
      chorioretinopathy (CSC).Patients and methodsThirty-eight eyes of 33 patients with
      CSC were analyzed retrospectively. Key inclusion criteria were naive (acute or
      recurrent) CSC; a minimum of 12 months of follow up; and the availability of good
      quality enhanced depth imaging SD-OCT images at each visit. Eyes with changes
      suggestive of chronic CSC and history of any treatment were excluded. Collected
      data included demographic profile, visual acuity, subfoveal CT, central macular
      thickness (CMT), and treatment details. Univariate and multivariate analyses for
      association of baseline features with need for treatment were performed. On the
      basis of results of this analysis, the 38 eyes were divided into two groups:
      Group A (subfoveal CT<=356 MUm) and Group B (subfoveal CT>356 MUm).ResultsOn
      univariate analysis, the need for treatment had significantly positive
      correlation with duration of symptoms (P=0.02), negative correlation with the
      baseline CT (P<0.01), and no significant correlation with CMT (P=0.13). On
      multivariate regression analysis, only baseline CT had a statistically
      significant association with the need for treatment (odds ratio (OR), 0.989; CI,
      0.979-0.999; P=0.048). Group A eyes were more likely to require treatment (Group
      A: 54.55%, 12 of 22 eyes; Group B: 18.75%, 3 of 16 eyes; OR: 5.2, 95% CI, 1.15
      23.54; P=0.04). There was a significant decrease in subfoveal CT in Group B (
      105.62+/-108.91 MUm; P=0.002).ConclusionCSC with a subfoveal CT<=356 MUm is of
      chronic nature and is more likely to require treatment rather than observation.

PMID- 27689966
TI  - Single-Layer Halide Perovskite Light-Emitting Diodes with Sub-Band Gap Turn-On
      Voltage and High Brightness.
AB  - Charge-carrier injection into an emissive semiconductor thin film can result in
      electroluminescence and is generally achieved by using a multilayer device
      structure, which requires an electron-injection layer (EIL) between the cathode
      and the emissive layer and a hole-injection layer (HIL) between the anode and the
      emissive layer. The recent advancement of halide perovskite semiconductors opens
      up a new path to electroluminescent devices with a greatly simplified device
      structure. We report cesium lead tribromide light-emitting diodes (LEDs) without
      the aid of an EIL or HIL. These so-called single-layer LEDs have exhibited a sub
      band gap turn-on voltage. The devices obtained a brightness of 591 197 cd m-2 at
      4.8 V, with an external quantum efficiency of 5.7% and a power efficiency of 14.1
      lm W-1. Such an advancement demonstrates that very high efficiency of electron
      and hole injection can be obtained in perovskite LEDs even without using an EIL
      or HIL.

PMID- 27689967
TI  - Recent Advances in the Determination of Biogenic Amines in Food Samples by
      (U)HPLC.
AB  - The determination of biogenic amines (BAs) in food products stirs increasing
      interest because of the implications in toxicological and food quality issues.
      Apart from these aspects, in recent years, the relevance of BAs because of some
      organoleptic and descriptive concerns has been pointed out by several
      researchers. This overview aims at revising recent advances in the determination
      of BAs in food samples based on liquid chromatography. In particular, papers
      published in the past five years have been commented. Special attention has been
      paid to the great possibilities of ultrahigh-performance liquid chromatography
      and high-resolution mass spectrometry. With regard to applications, apart from
      the determination of BAs in a wide range of food matrices, novel lines of
      research focused on the characterization, classification, and authentication of
      food products based on chemometrics have also been discussed.

PMID- 27689968
TI  - Asymmetrically Functionalized Antibody-Gold Nanoparticle Conjugates to Form
      Stable Antigen-Assembled Dimers.
AB  - Biomolecular assays based on the aggregation of modified gold nanoparticles
      (AuNPs) have been developed to provide low detection limits and rapid results
      with a simple one-step, wash-free procedure. However, a relatively narrow dynamic
      range, low sensitivity, and poor precision due to time-sensitive readout limit
      the application of these assay platforms. In this work we synthesized
      asymmetrically functionalized antibody-AuNP conjugates that are rationally
      designed to overcome the limitations of aggregation-based immunoassays. Solid
      phase synthesis was used to chemically passivate the majority of the AuNP surface
      and restrict antibody immobilization into a small area of the AuNP surface. These
      asymmetric conjugates assembled into dimers with the addition of antigen and were
      stable for over 24 h. In contrast, conventional antibody-AuNP conjugates which
      are symmetrically modified with antibody assembled into large aggregates that
      continuously increased in size with the addition of target antigen. These results
      suggest that asymmetric antibody-AuNP conjugates have the potential to
      significantly improve the analytical performance of aggregation-based
      immunoassays.

PMID- 27689970
TI  - Enzymatic Synthesis of Glucose-Based Fatty Acid Esters in Bisolvent Systems
      Containing Ionic Liquids or Deep Eutectic Solvents.
AB  - Sugar fatty acid esters (SFAEs) are biocompatible nonionic surfactants with broad
      applications in food, cosmetic, and pharmaceutical industries. They can be
      synthesized enzymatically with many advantages over their chemical synthesis. In
      this study, SFAE synthesis was investigated by using two reactions: (1)
      transesterification of glucose with fatty acid vinyl esters and (2)
      esterification of methyl glucoside with fatty acids, catalyzed by Lipozyme TLIM
      and Novozym 435 respectively. Fourteen ionic liquids (ILs) and 14 deep eutectic
      solvents (DESs) were screened as solvents, and the bisolvent system composed of 1
      hexyl-3-methylimidazolium trifluoromethylsulfonate ([HMIm][TfO]) and 2-methyl-2
      butanol (2M2B) was the best for both reactions, yielding optimal productivities
      (769.6 and 397.5 umol/h/g, respectively) which are superior to those reported in
      the literature. Impacts of different reaction conditions were studied for both
      reactions. Response surface methodology (RSM) was employed to optimize the
      transesterification reaction. Results also demonstrated that as co-substrate,
      methyl glucoside yielded higher conversions than glucose, and that conversions
      increased with an increase in the chain length of the fatty acid moieties. DESs
      were poor solvents for the above reactions presumably due to their high viscosity
      and high polarity.

PMID- 27689969
TI  - An international randomised controlled trial to compare TARGeted Intraoperative
      radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast
      conserving surgery for women with early-stage breast cancer (the TARGIT-A trial).
AB  - BACKGROUND: Based on our laboratory work and clinical trials we hypothesised that
      radiotherapy after lumpectomy for breast cancer could be restricted to the tumour
      bed. In collaboration with the industry we developed a new radiotherapy device
      and a new surgical operation for delivering single-dose radiation to the tumour
      bed - the tissues at highest risk of local recurrence. We named it TARGeted
      Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and
      safety in pilot studies. OBJECTIVE: To compare TARGIT within a risk-adapted
      approach with whole-breast external beam radiotherapy (EBRT) over several weeks.
      DESIGN: The TARGeted Intraoperative radioTherapy Alone (TARGIT-A) trial was a
      pragmatic, prospective, international, multicentre, non-inferiority, non-blinded,
      randomised (1 : 1 ratio) clinical trial. Originally, randomisation occurred
      before initial lumpectomy (prepathology) and, if allocated TARGIT, the patient
      received it during the lumpectomy. Subsequently, the postpathology stratum was
      added in which randomisation occurred after initial lumpectomy, allowing
      potentially easier logistics and a more stringent case selection, but which
      needed a reoperation to reopen the wound to give TARGIT as a delayed procedure.
      The risk-adapted approach meant that, in the experimental arm, if pre-specified
      unsuspected adverse factors were found postoperatively after receiving TARGIT,
      EBRT was recommended. Pragmatically, this reflected how TARGIT would be practised
      in the real world. SETTING: Thirty-three centres in 11 countries. PARTICIPANTS:
      Women who were aged >= 45 years with unifocal invasive ductal carcinoma
      preferably <= 3.5 cm in size. INTERVENTIONS: TARGIT within a risk-adapted
      approach and whole-breast EBRT. MAIN OUTCOME MEASURES: The primary outcome
      measure was absolute difference in local recurrence, with a non-inferiority
      margin of 2.5%. Secondary outcome measures included toxicity and breast cancer
      specific and non-breast-cancer mortality. RESULTS: In total, 3451 patients were
      recruited between March 2000 and June 2012. The following values are 5-year
      Kaplan-Meier rates for TARGIT compared with EBRT. There was no statistically
      significant difference in local recurrence between TARGIT and EBRT. TARGIT was
      non-inferior to EBRT overall [TARGIT 3.3%, 95% confidence interval (CI) 2.1% to
      5.1% vs. EBRT 1.3%, 95% CI 0.7% to 2.5%; p = 0.04; Pnon-inferiority = 0.00000012]
      and in the prepathology stratum (n = 2298) when TARGIT was given concurrently
      with lumpectomy (TARGIT 2.1%, 95% CI 1.1% to 4.2% vs. EBRT 1.1%, 95% CI 0.5% to
      2.5%; p = 0.31; Pnon-inferiority = 0.0000000013). With delayed TARGIT
      postpathology (n = 1153), the between-group difference was larger than 2.5% and
      non-inferiority was not established for this stratum (TARGIT 5.4%, 95% CI 3.0% to
      9.7% vs. EBRT 1.7%, 95% CI 0.6% to 4.9%; p = 0.069; Pnon-inferiority = 0.06640].
      The local recurrence-free survival was 93.9% (95% CI 90.9% to 95.9%) when TARGIT
      was given with lumpectomy compared with 92.5% (95% CI 89.7% to 94.6%) for EBRT (p
      = 0.35). In a planned subgroup analysis, progesterone receptor (PgR) status was
      found to be the only predictor of outcome: hormone-responsive patients (PgR
      positive) had similar 5-year local recurrence with TARGIT during lumpectomy
      (1.4%, 95% CI 0.5% to 3.9%) as with EBRT (1.2%, 95% CI 0.5% to 2.9%; p = 0.77).
      Grade 3 or 4 radiotherapy toxicity was significantly reduced with TARGIT.
      Overall, breast cancer mortality was much the same between groups (TARGIT 2.6%,
      95% CI 1.5% to 4.3% vs. EBRT 1.9%, 95% CI 1.1% to 3.2%; p = 0.56) but there were
      significantly fewer non-breast-cancer deaths with TARGIT (1.4%, 95% CI 0.8% to
      2.5% vs. 3.5%, 95% CI 2.3% to 5.2%; p = 0.0086), attributable to fewer deaths
      from cardiovascular causes and other cancers, leading to a trend in reduced
      overall mortality in the TARGIT arm (3.9%, 95% CI 2.7% to 5.8% vs. 5.3%, 95% CI
      3.9% to 7.3%; p = 0.099]. Health economic analyses suggest that TARGIT was
      statistically significantly less costly than EBRT, produced similar quality
      adjusted life-years, had a positive incremental net monetary benefit that was
      borderline statistically significantly different from zero and had a probability
      of > 90% of being cost-effective. There appears to be little uncertainty in the
      point estimates, based on deterministic and probabilistic sensitivity analyses.
      If TARGIT were given instead of EBRT in suitable patients, it might potentially
      reduce costs to the health-care providers in the UK by L8-9.1 million each year.
      This does not include environmental, patient and societal costs. LIMITATIONS: The
      number of local recurrences is small but the number of events for local
      recurrence-free survival is not as small (TARGIT 57 vs. EBRT 59); occurrence of
      so few events (< 3.5%) also implies that both treatments are effective and any
      difference is unlikely to be large. Not all 3451 patients were followed up for 5
      years; however, more than the number of patients required to answer the main
      trial question (n = 585) were followed up for > 5 years. CONCLUSIONS: For
      patients with breast cancer (women who are aged >= 45 years with hormone
      sensitive invasive ductal carcinoma that is up to 3.5 cm in size), TARGIT
      concurrent with lumpectomy within a risk-adapted approach is as effective as,
      safer than and less expensive than postoperative EBRT. FUTURE WORK: The analyses
      will be repeated with longer follow-up. Although this may not change the primary
      result, the larger number of events may confirm the effect on overall mortality
      and allow more detailed subgroup analyses. The TARGeted Intraoperative
      radioTherapy Boost (TARGIT-B) trial is testing whether or not a tumour bed boost
      given intraoperatively (TARGIT) boost is superior to a tumour bed boost given as
      part of postoperative EBRT. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN34086741 and ClinicalTrials.gov NCT00983684. FUNDING: University College
      London Hospitals (UCLH)/University College London (UCL) Comprehensive Biomedical
      Research Centre, UCLH Charities, Ninewells Cancer Campaign, National Health and
      Medical Research Council and German Federal Ministry of Education and Research
      (BMBF). From September 2009 this project was funded by the NIHR Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment; Vol. 20, No. 73. See the NIHR Journals Library website for further
      project information.

PMID- 27689971
TI  - Glycyrrhizic Acid Reduces Heart Rate and Blood Pressure by a Dual Mechanism.
AB  - Beta adrenergic receptors are crucial for their role in rhythmic contraction of
      heart along with their role in the pathological conditions such as tachycardia
      and high risk of heart failure. Studies report that the levels of beta-1
      adrenergic receptor tend to decrease by 50%, whereas, the levels of beta-2
      adrenergic receptor remains constant during the risk of heart failure. Beta
      blockers-the antagonistic molecules for beta-adrenergic receptors, function by
      slowing the heart rate, which thereby allows the left ventricle to fill
      completely during tachycardia incidents and hence helps in blood pumping capacity
      of heart and reducing the risk of heart failure. In the present study, we
      investigate the potential of glycyrrhizic acid (GA) as a possible principal drug
      molecule for cardiac arrhythmias owing to its ability to induce reduction in the
      heart rate and blood pressure. We use in vitro and in silico approach to study
      GA's effect on beta adrenergic receptor along with an in vivo study to examine
      its effect on heart rate and blood pressure. Additionally, we explore GA's
      proficiency in eliciting an increase in the plasma levels of vasoactive
      intestinal peptide, which by dilating the blood vessel consequently, can be a
      crucial aid during the occurrence of a potential heart attack. Therefore, we
      propose GA as a potential principal drug molecule via its potential in modulating
      heart rate and blood pressure.

PMID- 27689972
TI  - CO Oxidation over Pd/ZrO2 Catalysts: Role of Support's Donor Sites.
AB  - A series of supported Pd/ZrO2 catalysts with Pd loading from 0.2 to 2 wt % was
      synthesized. The ZrO2 material prepared by a similar technique was used as a
      reference sample. The samples have been characterized by means of transmission
      electron microscopy (TEM), X-ray diffraction analysis (XRD), X-ray photoelectron
      spectroscopy (XPS), temperature-programmed reduction (TPR), testing reaction of
      ethane hydrogenolysis (HGE), N2 adsorption, and electron paramagnetic resonance
      (EPR) spectroscopy. 1,3,5-trinitrobenzene was used as a probe molecule for the
      EPR spin probe method. The catalytic performance of samples was tested in the
      model reaction of CO oxidation. It was shown that the concentration of donor
      sites of support measured by EPR spin probe correlates with catalytic behavior
      during light-off tests. Low concentration of donor sites on a support's surface
      was found to be caused by the presence of the specific surface defects that are
      related to existence of coordinately unsaturated structures.

PMID- 27689973
TI  - Design, Synthesis, and Cytotoxicity of 5-Fluoro-2-methyl-6-(4-aryl-piperazin-1
      yl) Benzoxazoles.
AB  - To design new compounds suitable as starting points for anticancer drug
      development, we have synthesized a novel series of benzoxazoles with
      pharmaceutically advantageous piperazine and fluorine moieties attached to them.
      The newly synthesized benzoxazoles and their corresponding precursors were
      evaluated for cytotoxicity on human A-549 lung carcinoma cells and non-cancer
      HepaRG hepatocyes. Some of these new benzoxazoles show potential anticancer
      activity, while two of the intermediates show lung cancer selective properties at
      low concentrations where healthy cells are unaffected, indicating a selectivity
      window for anticancer compounds.

PMID- 27689974
TI  - Cordycepin Induces Apoptosis and Inhibits Proliferation of Human Lung Cancer Cell
      Line H1975 via Inhibiting the Phosphorylation of EGFR.
AB  - Cordycepin is an active component of the traditional Chinese medicine Cordyceps
      sinensis and Cordyceps militaris with notable anticancer activity. Though the
      prominent inhibitory activity was reported in different kinds of cancer cell
      lines, the concrete mechanisms remain elusive. It was reported that cordycepin
      could be converted into tri-phosphates in vivo to confuse a number of enzymes and
      interfere the normal cell function. For the inhibitory mechanism of EGFR
      inhibitors and the structure similarity of ATP and tri-phosphated cordycepin,
      human lung cancer cell line H1975 was employed to investigate the inhibitory
      effect of cordycepin. The results showed that cordycepin could inhibit cell
      proliferation and induce apoptosis in a dose-dependent manner. Cell cycle
      analysis revealed that H1975 cells could be arrested at the G0/G1 phase after
      cordycepin treatment. The expression levels of apoptosis-related protein Caspase
      3 and Bcl-2 and phosphorylated expression levels of EGFR, AKT and ERK1/2 were all
      decreased compared with the control group stimulated with EGF. However, the
      protein expression levels of proapoptotic protein Bax and cleaved caspase-3 were
      increased. These results implied that cordycepin could inhibit cell proliferation
      and induce apoptosis via the EGFR signaling pathway. Our results indicated that
      there was potential to seek a novel EGFR inhibitor from cordycepin and its
      chemical derivatives.

PMID- 27689975
TI  - Phytochemical Compositions of Immature Wheat Bran, and Its Antioxidant Capacity,
      Cell Growth Inhibition, and Apoptosis Induction through Tumor Suppressor Gene.
AB  - The purpose of this study was to investigate the phytochemical compositions and
      antioxidant capacity, cell growth inhibition, and apoptosis induction in extracts
      of immature wheat bran. Immature wheat bran (IWB) was obtained from immature
      wheat harvested 10 days earlier than mature wheat. The phytochemical compositions
      of bran extract samples were analyzed by ultra-high performance liquid
      chromatography. The total ferulic acid (3.09 mg/g) and p-coumaric acid (75 ug/g)
      in IWB were significantly higher than in mature wheat bran (MWB, ferulic acid:
      1.79 mg/g; p-coumaric acid: 55 ug/g). The oxygen radical absorbance capacity
      (ORAC: 327 uM Trolox equivalents (TE)/g) and cellular antioxidant activity (CAA:
      4.59 uM Quercetin equivalents (QE)/g) of the IWB were higher than those of the
      MWB (ORAC: 281 uM TE/g; CAA: 0.63 uM QE/g). When assessing cell proliferation,
      the IWB extracts resulted in the lowest EC50 values against HT-29 (18.9 mg/mL),
      Caco-2 (7.74 mg/mL), and HeLa cells (8.17 mg/mL) among bran extract samples.
      Additionally, the IWB extracts increased the gene expression of p53 and PTEN
      (tumor suppressor genes) in HT-29 cells, indicating inhibited cell growth and
      induced apoptosis through tumor suppressor genes.

PMID- 27689976
TI  - Structural Characterization of the Avidin Interactions with Fluorescent Pyrene
      Conjugates: 1-Biotinylpyrene and 1-Desthiobiotinylpyrene.
AB  - Avidin is a tetrameric protein that belongs to the calycin superfamily. It has
      been studied mainly because of its extraordinary affinity to biotin, which led to
      a wide range of applications based on the avidin-biotin system. In the present
      study, we report the first crystal structures of avidin in a complex with two
      novel fluorescent pyrene derivatives: 1-biotinylpyrene (B9P) and 1
      desthiobiotinylpyrene (D9P). The crystal structures were solved by molecular
      replacement using the coordinates of avidin molecule as a starting model and the
      final models of avidin/B9P and avidin/D9P were refined to resolutions of 2.0 A
      and 2.1 A, respectively. Our data reveal changes in loop conformation as well as
      in overall fold and quaternary arrangement of the avidin upon the binding of
      these fluorescent probes. Moreover, the crystal structures allowed analysis of
      the details of the interactions between the protein and the pyrene derivatives.
      Structural description of the complexes will contribute to the design of
      conjugates for expanding the capabilities of avidin-biotin technology.

PMID- 27689977
TI  - Group I Intron Internal Guide Sequence Binding Strength as a Component of
      Ribozyme Network Formation.
AB  - Origins-of-life research requires searching for a plausible transition from
      simple chemicals to larger macromolecules that can both hold information and
      catalyze their own production. We have previously shown that some group I intron
      ribozymes possess the ability to help synthesize other ribozyme genotypes by
      recombination reactions in small networks in an autocatalytic fashion. By
      simplifying these recombination reactions, using fluorescent anisotropy, we
      quantified the thermodynamic binding strength between two nucleotides of two
      group I intron RNA fragments for all 16 possible genotype combinations. We
      provide evidence that the binding strength (KD) between the 3-nucleotide internal
      guide sequence (IGS) of one ribozyme and its complement in another is correlated
      to the catalytic ability of the ribozyme. This work demonstrates that one can
      begin to deconstruct the thermodynamic basis of information in prebiotic RNA
      systems.

PMID- 27689978
TI  - Identification of the Main Intermediate Precursor of l-Ergothioneine Biosynthesis
      in Human Biological Specimens.
AB  - A capillary electrophoresis coupled to tandem mass spectrometry (CE-MS/MS) has
      been used to make a qualitative determination of hercynine-the main precursor of
      l-ergothioneine biosynthesis-in some key human biological specimens, such as
      urine, whole blood, plasma, and saliva. From semiquantitative analysis results,
      the highest concentrations of hercynine were detected in saliva and whole blood,
      whereas much lower concentrations were measured in urine and plasma. Whole blood
      was the biological matrix with the highest concentration of l-ergothioneine
      followed by plasma, saliva, and urine. The antioxidant effects attributed to l
      ergothioneine, along with its peculiar antioxidant mechanism, offer a possible
      explanation for the presence of the hercynine, as well as its concentration, in
      the considered biological matrices.

PMID- 27689979
TI  - Palladium-Catalyzed Allylation/Benzylation of H-Phosphinate Esters with Alcohols.
AB  - The Pd-catalyzed direct alkylation of H-phosphinic acids and hypophosphorous acid
      with allylic/benzylic alcohols has been described previously. Here, the extension
      of this methodology to H-phosphinate esters is presented. The new reaction
      appears general, although its scope is narrower than with the acids, and its
      mechanism is likely different. Various alcohols are examined in their reaction
      with phosphinylidene compounds R1R2P(O)H.

PMID- 27689980
TI  - Advances in Organic and Organic-Inorganic Hybrid Polymeric Supports for Catalytic
      Applications.
AB  - In this review, the most recent advances (2014-2016) on the synthesis of new
      polymer-supported catalysts are reported, focusing the attention on the synthetic
      strategies developed for their preparation. The polymer-supported catalysts
      examined will be organic-based polymers and organic-inorganic hybrids and will
      include, among others, polystyrenes, poly-ionic liquids, chiral ionic polymers,
      dendrimers, carbon nanotubes, as well as silica and halloysite-based catalysts.
      Selected examples will show the synthesis and application in the field of
      organocatalysis and metal-based catalysis both for non-asymmetric and asymmetric
      transformations.

PMID- 27689981
TI  - New Diphenol and Isocoumarins from the Aerial Part of Lawsonia inermis and Their
      Inhibitory Activities against NO Production.
AB  - Lawsonia inermis Linn (Lythraceae), also known as henna, is a small shrub or tree
      distributed throughout Taiwan's Lanyu Island, in North Africa, and in Australia.
      Its leaves are used as a folk medicine for the treatment of external hemorrhage
      and fingernail abscesses. Investigation of the ethyl acetate (EtOAc)-soluble
      fractions from methanol extract of the aerial part of Lawsonia inermis has led to
      the isolation of a new diphenol, (Z)-4,4'-(prop-1-ene-1,3-diyl)diphenol (1), two
      new isocoumarin carbonates, inermiscarbonates A (2) and B (3), and six known
      compounds, 4'-hydroxyflavanone (4), apigenine (5), kampferol (6), luteolin (7),
      quercetin (8), and (-)-catechin (9). Their structures were determined by detailed
      analysis of spectroscopic data and comparison with the data of known analogues.
      Compounds 1 and 4-9 were evaluated for the inhibition of nitric oxide production
      in lipopolysaccharide (LPS)-stimulated product of nitrite in RAW 264.7 cells with
      IC50 values of 5.63, 15.72, 8.67, 6.67, 6.17, 7.61, and 14.52 MUg/mL,
      respectively.

PMID- 27689983
TI  - Catalytic Synthesis of a New Series of Alkyl Uronates and Evaluation of Their
      Physicochemical Properties.
AB  - Large quantities (>3 g) of a new series of alkyl uronates were synthesized in two
      steps from commercial methyl hexopyranosides. Firstly, several tens of grams of
      free methyl alpha-d-glucopyranoside were selectively and quantitatively oxidized
      into corresponding sodium uronate using 2,2,6,6-tetramethyl-1-piperidinyloxy free
      radical (TEMPO)-catalyzed oxidation. Hydrophobic chains of different length were
      then introduced by acid-mediated esterification with fatty alcohols (ethyl to
      lauryl alcohol) leading to the desired alkyl glucuronates with moderate to good
      yields (49%-72%). The methodology was successfully applied to methyl alpha-d
      mannopyranoside and methyl beta-d-galactopyranoside. Physicochemical properties,
      such as critical micelle concentration (CMC), equilibrium surface tension at CMC
      (gammacmc), solubility, and Krafft temperature were measured, and the effect of
      structural modifications on surface active properties and micelle formation was
      discussed.

PMID- 27689982
TI  - Constituents of Cryptotaenia japonica Inhibit Melanogenesis via CREB- and MAPK
      Associated Signaling Pathways in Murine B16 Melanoma Cells.
AB  - Melanin plays an important role in protecting the skin against ultraviolet light
      and is responsible for skin color. However, overproduction of melanin is related
      to several skin disorders, such as age spots, freckles, cafe au lait spots,
      Becker's nevus and other hyperpigmentation syndromes. The aim of this study was
      to identify the effects of kaempferol-7-O-beta-d-glucuronide (K7G) and tilianin,
      isolated from Cryptotaenia japonica, on melanogenesis and their mechanisms of
      action in murine B16 melanoma cells. The alpha-melanocyte-stimulating hormone
      (alpha-MSH)-induced melanin production was significantly inhibited by K7G and
      tilianin in a dose-dependent manner. The effects of these compounds on the
      signaling pathway of melanogenesis were examined. K7G and tilianin downregulated
      the expression of microphthalmia-associated transcription factor (MITF) and
      melanocyte-specific enzymes, i.e., tyrosinase and TRP1. These compounds also
      inhibited the phosphorylation of cyclic adenosine monophosphate (cAMP)-response
      element binding protein (CREB) in a dose-dependent manner. In addition, these
      compounds increased the phosphorylation of extracellular signal-regulated kinase
      (ERK) but decreased the phosphorylation of c-Jun N-terminal kinase (JNK) in B16
      cells. Based on the above results, the anti-melanogenic effects of these
      compounds are caused by suppression of the MAPK signaling pathway through the
      down-regulation of alpha-MSH-induced CREB accumulation. This finding suggests
      that K7G and tilianin may be good candidates for further research to develop
      therapeutic agents for hyperpigmentation diseases.

PMID- 27689984
TI  - Flavonoid Interaction with a Chitinase from Grape Berry Skin: Protein
      Identification and Modulation of the Enzymatic Activity.
AB  - In the present study, an antibody raised against a peptide sequence of rat
      bilitranslocase (anti-peptide Ab) was tested on microsomal proteins obtained from
      red grape berry skin. Previously, this antibody had demonstrated to recognize
      plant membrane proteins associated with flavonoid binding and transport. Immuno
      proteomic assays identified a number of proteins reacting with this particular
      antibody, suggesting that the flavonoid binding and interaction may be extended
      not only to carriers of these molecules, but also to enzymes with very different
      functions. One of these proteins is a pathogenesis-related (PR) class IV
      chitinase, whose in vitro chitinolytic activity was modulated by two of the most
      representative flavonoids of grape, quercetin and catechin, as assessed by both
      spectrophotometric and fluorimetric assays in grape microsomes and commercial
      enzyme preparations. The effect of these flavonoids on the catalysis and its
      kinetic parameters was also evaluated, evidencing that they determine a hormetic
      dose-dependent response. These results highlight the importance of flavonoids not
      only as antioxidants or antimicrobial effectors, but also as modulators of plant
      growth and stress response. Implications of the present suggestion are here
      discussed in the light of environment and pesticide-reduction concerns.

PMID- 27689985
TI  - Beneficial Effects of Tea and the Green Tea Catechin Epigallocatechin-3-gallate
      on Obesity.
AB  - Green tea has been shown to have beneficial effects against cancer, obesity,
      atherosclerosis, diabetes, bacterial and viral infections, and dental caries. The
      catechin (-)-epigallocatechin-3-gallate (EGCG) has shown the highest biological
      activity among green tea catechins (GTCs) in most of the studies. While several
      epidemiological studies have shown the beneficial effects of tea and GTCs on
      obesity, some studies have failed to do this. In addition, a large number of
      interventional clinical studies have shown these favorable effects, and cellular
      and animal experiments have supported those findings, and revealed the underlying
      anti-obesity mechanisms. One of the mechanisms is enhanced cellular production of
      reactive oxygen species, which is mediated through the pro-oxidant action of
      EGCG, leading to the activation of adenosine monophosphate-activated protein
      kinase, which suppresses gene and protein expression of enzymes and transcription
      factors involved in adipogenesis and lipogenesis, and stimulates those involved
      in lipolysis. Recently, scientific evidence supporting the beneficial anti
      obesity effects of green tea and GTCs has been increasing. However, future
      investigations are still required to clarify the reasons for the inconsistent
      results reported in the human studies; to achieve this, careful adjustment of
      confounding factors will be required.

PMID- 27689986
TI  - Traceability of Satsuma Mandarin (Citrus unshiu Marc.) Honey through Nectar/Honey
      Sac/Honey Pathways of the Headspace, Volatiles, and Semi-Volatiles: Chemical
      Markers.
AB  - Headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction
      (USE), followed by GC-MS/FID, were applied for monitoring the nectar (NE)/honey
      sac (HoS)/honey (HO) pathways of the headspace, volatiles, and semi-volatiles.
      The major NE (4 varieties of Citrus unshiu) headspace compounds were linalool,
      alpha-terpineol, 1H-indole, methyl anthranilate, and phenylacetonitrile.
      Corresponding extracts contained, among others, 1H-indole, methyl anthranilate,
      1,3-dihydro-2H-indol-2-one and caffeine. The major HoS headspace compounds were
      linalool, alpha-terpineol, 1,8-cineole, 1H-indole, methyl anthranilate, and cis
      jasmone. Characteristic compounds from HoS extract were caffeine, 1H-indole, 1,3
      dihydro-2H-indol-2-one, methyl anthranilate, and phenylacetonitrile. However, HO
      headspace composition was significantly different in comparison to NE and HoS
      with respect to phenylacetaldehyde and linalool derivatives abundance that
      appeared as the consequence of the hive conditions and the bee enzyme activity.
      C. unshiu honey traceability is determined by chemical markers:
      phenylacetaldehyde, phenylacetonitrile, linalool and its derivatives, as well as
      1H-indole, 1,3-dihydro-2H-indol-2-one, and caffeine.

PMID- 27689987
TI  - Mining Chromatographic Enantioseparation Data Using Matched Molecular Pair
      Analysis.
AB  - We apply matched molecular pair (MMP) analysis to data from ChirBase, which
      contains literature reports of chromatographic enantioseparations. For the 19
      chiral stationary phases we examined, we were able to identify 289 sets of pairs
      where there is a statistically significant and consistent difference in
      enantioseparation due to a small chemical change. In many cases these changes
      highlight enantioselectivity differences between pairs or small families of
      closely related molecules that have for many years been used to probe the
      mechanisms of chromatographic chiral recognition; for example, the comparison of
      N-H vs. N-Me analytes to determine the criticality of an N-H hydrogen bond in
      chiral molecular recognition. In other cases, statistically significant MMPs
      surfaced by the analysis are less familiar or somewhat puzzling, sparking a need
      to generate and test hypotheses to more fully understand. Consequently, mining of
      appropriate datasets using MMP analysis provides an important new approach for
      studying and understanding the process of chromatographic enantioseparation.

PMID- 27689988
TI  - Increasing the Level of IRS-1 and Insulin Pathway Sensitivity by Natural Product
      Carainterol A.
AB  - Carainterol A is a eudesmane sesquiterpenoid extracted from Caragana intermedia.
      We have reported that carainterol A showed potent glucose consumption activity in
      C2C12 muscle cells and the db/db mouse model. However, the mechanism of the
      hypoglycemic effect of carainterol A remains elusive. In this article, we present
      a network pharmacology approach to predict the target and signaling pathway of
      carainterol A which was subsequently validated in HepG2 cells. It was
      demonstrated that carainterol A could increase the protein levels of IRS-1 and
      the downstream protein kinase AKT phosphorylation at a low micromolar level.
      These findings suggest that carainterol A can be a valuable lead compound and a
      promising chemical probe for the insulin signaling pathway.

PMID- 27689989
TI  - Chlorella sorokiniana Extract Improves Short-Term Memory in Rats.
AB  - Increasing evidence shows that eukaryotic microalgae and, in particular, the
      green microalga Chlorella, can be used as natural sources to obtain a whole
      variety of compounds, such as omega (omega)-3 and omega-6 polyunsatured fatty
      acids (PUFAs). Although either beneficial or toxic effects of Chlorella
      sorokiniana have been mainly attributed to its specific omega-3 and omega-6 PUFAs
      content, the underlying molecular pathways remain to be elucidated yet. Here, we
      investigate the effects of an acute oral administration of a lipid extract of
      Chlorella sorokiniana, containing mainly omega-3 and omega-6 PUFAs, on cognitive,
      emotional and social behaviour in rats, analysing possible underlying
      neurochemical alterations. Our results showed improved short-term memory in
      Chlorella sorokiniana-treated rats compared to controls, without any differences
      in exploratory performance, locomotor activity, anxiety profile and depressive
      like behaviour. On the other hand, while the social behaviour of Chlorella
      sorokiniana-treated animals was significantly decreased, no effects on
      aggressivity were observed. Neurochemical investigations showed region-specific
      effects, consisting in an elevation of noradrenaline (NA) and serotonin (5-HT)
      content in hippocampus, but not in the prefrontal cortex and striatum. In
      conclusion, our results point towards a beneficial effect of Chlorella
      sorokiniana extract on short-term memory, but also highlight the need of caution
      in the use of this natural supplement due to its possible masked toxic effects.

PMID- 27689990
TI  - Homeodomain-Interacting Protein Kinase-2: A Critical Regulator of the DNA Damage
      Response and the Epigenome.
AB  - Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine kinase
      that phosphorylates and activates the apoptotic program through interaction with
      diverse downstream targets including tumor suppressor p53. HIPK2 is activated by
      genotoxic stimuli and modulates cell fate following DNA damage. The DNA damage
      response (DDR) is triggered by DNA lesions or chromatin alterations. The DDR
      regulates DNA repair, cell cycle checkpoint activation, and apoptosis to restore
      genome integrity and cellular homeostasis. Maintenance of the DDR is essential to
      prevent development of diseases caused by genomic instability, including cancer,
      defects of development, and neurodegenerative disorders. Recent studies reveal a
      novel HIPK2-mediated pathway for DDR through interaction with chromatin
      remodeling factor homeodomain protein 1gamma. In this review, we will highlight
      the molecular mechanisms of HIPK2 and show its functions as a crucial DDR
      regulator.

PMID- 27689991
TI  - MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting
      Recepteur d'Origine Nantais.
AB  - Emerging evidence supports a fundamental role for microRNAs (miRNA) in regulating
      cancer metastasis. Recently, microRNA-375 (miR-375) was reported to be
      downregulated in many types of cancers, including gastric cancer. Increase in the
      expression of Recepteur d'Origine Nantais (RON), a receptor tyrosine kinase, has
      been reported in tumors. However, the function of miR-375 and RON expression in
      gastric cancer metastasis has not been sufficiently studied. In silico analysis
      identified miR-375 binding sites in the 3'-untranslated regions (3'-UTR) of the
      RON-encoding gene. Expression of miR-375 resulted in reduced activity of a
      luciferase reporter containing the 3'-UTR fragments of RON-encoding mRNA,
      confirming that miR-375 directly targets the 3'-UTR of RON mRNA. Moreover, we
      found that overexpression of miR-375 inhibited mRNA and protein expression of
      RON, which was accompanied by the suppression of cell proliferation, migration,
      and invasion in gastric cancer AGS and MKN-28 cells. Ectopic miR-375 expression
      also induced G1 cell cycle arrest through a decrease in the expression of cyclin
      D1, cyclin D3, and in the phosphorylation of retinoblastoma (Rb). Knockdown of
      RON by RNAi, similar to miR-375 overexpression, suppressed tumorigenic properties
      and induced G1 arrest through a decrease in the expression of cyclin D1, cyclin
      D3, and in the phosphorylation of Rb. Thus, our study provides evidence that miR
      375 acts as a suppressor of metastasis in gastric cancer by targeting RON, and
      might represent a new potential therapeutic target for gastric cancer.

PMID- 27689992
TI  - Urine Levels of Defensin alpha1 Reflect Kidney Injury in Leptospirosis Patients.
AB  - Leptospirosis is a zoonotic disease whose severe forms are often accompanied by
      kidney dysfunction. In the present study, urinary markers were studied for
      potential prediction of disease severity. Urine samples from 135 patients with or
      without leptospirosis at San Lazaro Hospital, the Philippines, were analyzed.
      Urine levels of defensin alpha1 (uDA1) were compared with those of neutrophil
      gelatinase-associated lipocalin (uNGAL) and N-acetyl-beta-d-glucosidase (uNAG).
      Serum creatinine (Cr) was used as a marker of kidney injury. The levels of
      uDA1/Cr, uNGAL/Cr, and uNAG/Cr were positive in 46%, 90%, and 80% of
      leptospirosis patients, and 69%, 70%, and 70% of non-leptospirosis patients,
      respectively. In leptospirosis patients, the correlation of uDA1/Cr, uNGAL/Cr and
      uNAG/Cr levels with serum Cr were r = 0.3 (p < 0.01), r = 0.29 (p < 0.01), and r
      = 0.02 (p = 0.81), respectively. uDA1/Cr levels were correlated with uNGAL/Cr
      levels (r = 0.49, p < 0.01) and uNAG/Cr levels (r = 0.47, p < 0.0001) in
      leptospirosis patients. These findings suggest that uDA1, uNGAL, and uNAG were
      elevated in leptospirosis patients and reflected various types of kidney damage.
      uDA1 and uNGAL can be used to track kidney injury in leptospirosis patients
      because of their correlation with the serum Cr level.

PMID- 27689993
TI  - Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric
      Cancer after Gastrectomy.
AB  - Calpain-4 belongs to the calpain family of calcium-dependent cysteine proteases,
      and functions as a small regulatory subunit of the calpains. Recent evidence
      indicates that calpain-4 plays critical roles in tumor migration and invasion.
      However, the roles of calpain-4 in gastric tumorigenesis remain poorly
      understood. Herein, we examined calpain-4 expression by immunohistochemical
      staining on tissue microarrays containing tumor samples of 174 gastric cancer
      patients between 2004 and 2008 at a single center. The Kaplan-Meier method was
      used to compare survival curves, and expression levels were correlated to
      clinicopathological factors and overall survival. Our data demonstrated that
      calpain-4 was generally increased in gastric cancer cell lines and primary tumor
      tissues. High expression of calpain-4 was positively associated with vessel
      invasion, lymph node metastasis, and advanced TNM (Tumor Node Metastasis) stage.
      Multivariate analysis identified calpain-4 as an independent prognostic factor
      for poor prognosis. A predictive nomogram integrating calpain-4 expression with
      other independent prognosticators was constructed, which generated a better
      prognostic value for overall survival of gastric cancer patients than a TNM
      staging system. In conclusion, calpain-4 could be regarded as a potential
      prognosis indicator for clinical outcomes in gastric cancer.

PMID- 27689994
TI  - Selenomethionine Ameliorates Neuropathology in the Olfactory Bulb of a Triple
      Transgenic Mouse Model of Alzheimer's Disease.
AB  - Olfactory dysfunction is an early and common symptom in Alzheimer's disease (AD)
      and is reported to be related to several pathologic changes, including the
      deposition of Abeta and hyperphosphorylated tau protein as well as synaptic
      impairment. Selenomethionine (Se-Met), the major form of selenium in animals and
      humans, may be a promising therapeutic option for AD as it decreases the
      deposition of Abeta and tau hyperphosphorylation in a triple transgenic mouse
      model of AD (3* Tg-AD). In this study, 4-month-old AD mice were treated with 6
      ug/mL Se-Met in drinking water for 12 weeks and the effect of Se-Met on
      neuropathological deficits in olfactory bulb (OB) of 3* Tg-AD mice was
      investigated. The administration of Se-Met effectively decreased the production
      and deposition of Abeta by inhibiting beta-site amyloid precursor protein
      cleaving enzyme 1 (BACE1)-regulated amyloid precursor protein (APP) processing
      and reduced the level of total tau and phosphorylated tau, which depended on
      depressing the activity and expression of glycogen synthase kinase-3beta (GSK
      3beta) and cyclin-dependent kinase 5 (CDK5). Meanwhile, Se-Met reduced glial
      activation, relieved neuroinflammation and attenuated neuronal cell death in the
      OB of AD mice. So Se-Met could improve pathologic changes of AD in the OB, which
      further demonstrated the potential therapeutic effect of Se-Met in AD.

PMID- 27689995
TI  - Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3
      Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral
      Treated HIV-1 Infected Patients: A Pilot Study.
AB  - Recently the tryptophan pathway has been considered an important determinant of
      HIV-1 infected patients' quality of life, due to the toxic effects of its
      metabolites on the central nervous system (CNS). Since the dysbiosis described in
      HIV-1 patients might be responsible for the microbial translocation, the chronic
      immune activation, and the altered utilization of tryptophan observed in these
      individuals, we speculated a correlation between high levels of immune activation
      markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over
      expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface. In
      order to evaluate this issue, we measured the levels of neopterin in CSF, and the
      expression of IDO mRNA in gut-associated lymphoid tissue (GALT), in HIV-1
      infected patients on effective combined antiretroviral therapy (cART), at
      baseline and after six months of probiotic dietary management. We found a
      significant reduction of neopterin and IDO mRNA levels after the supplementation
      with probiotic. Since the results for the use of adjunctive therapies to reduce
      the levels of immune activation markers in CSF have been disappointing so far,
      our pilot study showing the efficacy of this specific probiotic product should be
      followed by a larger confirmatory trial.

PMID- 27689997
TI  - Preparation, Characterization and in Vivo Antimycobacterial Studies of
      Panchovillin-Chitosan Nanocomposites.
AB  - Chitosan (CS, molecular weight 20.2 kDa, degree of deacylation (DD) 73.31%) was
      successfully obtained by deacetylation of chitin extracted from shrimp
      (Litopenaeus vannamei) shell wastes. The encapsulation of the bioactive natural
      product, panchovillin (PANV), isolated from Erythrina schliebenii, on a chitosan
      tripolyphosphate (CS/TPP) nano-framework was achieved by ionotropic gelation.
      Characterization of pure CS, CS/TPP and PANV-CS/TPP nanocomposites was performed
      by FTIR, SEM and XRD. The molecular weight of chitosan and the thermal stability
      of the materials were determined by MALDI-TOF-MS and simultaneous thermal
      analyzer (STA)/DTG, respectively. The respective encapsulation efficiency and
      loading capacity of the PANV were found to be 70% and 0.36%. The in vitro release
      studies showed an initial burst of 42% of PANV in the first six hours. This was
      followed by a slow and sustained release up to 72 h. The in vivo
      antimycobacterial activities of both PANV and PANV-CS/TPP nanocomposite against
      Mycobacterium indicus pranii (MIP) using Galleria mellonella larvae as an in vivo
      infection model are reported in this paper.

PMID- 27689996
TI  - An Inflammatory Nucleus Pulposus Tissue Culture Model to Test Molecular
      Regenerative Therapies: Validation with Epigallocatechin 3-Gallate.
AB  - Organ cultures are practical tools to investigate regenerative strategies for the
      intervertebral disc. However, most existing organ culture systems induce severe
      tissue degradation with only limited representation of the in vivo processes. The
      objective of this study was to develop a space- and cost-efficient tissue culture
      model, which represents degenerative processes of the nucleus pulposus (NP).
      Intact bovine NPs were cultured in a previously developed system using Dyneema
      jackets. Degenerative changes in the NP tissue were induced either by the direct
      injection of chondroitinase ABC (1-20 U/mL) or by the diffusion of interleukin-1
      beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) (both 100 ng/mL) from
      the culture media. Extracellular matrix composition (collagens, proteoglycans,
      water, and DNA) and the expression of inflammatory and catabolic genes were
      analyzed. The anti-inflammatory and anti-catabolic compound epigallocatechin 3
      gallate (EGCG, 10 uM) was employed to assess the relevance of the degenerative NP
      model. Although a single injection of chondroitinase ABC reduced the proteoglycan
      content in the NPs, it did not activate cellular responses. On the other hand, IL
      1beta and TNF-alpha significantly increased the mRNA expression of inflammatory
      mediators IL-6, IL-8, inducible nitric oxide synthase (iNOS), prostaglandin
      endoperoxide synthase 2 (PTGS2) and matrix metalloproteinases (MMP1, MMP3, and
      MMP13). The cytokine-induced gene expression in the NPs was ameliorated with
      EGCG. This study provides a proof of concept that inflammatory NP cultures, with
      appropriate containment, can be useful for the discovery and evaluation of
      molecular therapeutic strategies against early degenerative disc disease.

PMID- 27689998
TI  - Isobaric Tags for Relative and Absolute Quantitation (iTRAQ)-Based Comparative
      Proteome Analysis of the Response of Ramie under Drought Stress.
AB  - In this study, we conducted the first isobaric tags for relative and absolute
      quantitation (isobaric tags for relative and absolute quantitation (iTRAQ))-based
      comparative proteomic analysis of ramie plantlets after 0 (minor drought stress),
      24 (moderate drought stress), and 72 h (severe drought stress) of treatment with
      15% (w/v) poly (ethylene glycol)6000 (PEG6000) to simulate drought stress. In our
      study, the association analysis of proteins and transcript expression revealed
      1244 and 968 associated proteins identified in leaves and roots, respectively.
      L1, L2, and L3 are leaf samples which were harvested at 0, 24, and 72 h after
      being treated with 15% PEG6000, respectively. Among those treatment groups, a
      total of 118, 216, and 433 unique proteins were identified as differentially
      expressed during L1 vs. L2, L2 vs. L3, and L1 vs. L3, respectively. R1, R2, and
      R3 are root samples which were harvested at 0, 24, and 72 h after being treated
      with 15% PEG6000, respectively. Among those treatment groups,a total of 124, 27,
      and 240 unique proteins were identified as differentially expressed during R1 vs.
      R2, R2 vs. R3, and R1 vs. R3, respectively. Bioinformatics analysis indicated
      that glycolysis/gluconeogenesis was significantly upregulated in roots in
      response to drought stress. This enhancement may result in more glycolytically
      generated adenosine triphosphate (ATP) in roots to adapt to adverse environmental
      conditions. To obtain complementary information related to iTRAQ data, the mRNA
      levels of 12 proteins related to glycolysis/gluconeogenesis in leaves and 7 in
      roots were further analyzed by qPCR. Most of their expression levels were higher
      in R3 than R1 and R2, suggesting that these compounds may promote drought
      tolerance by modulating the production of available energy.

PMID- 27689999
TI  - CAPS1 Negatively Regulates Hepatocellular Carcinoma Development through
      Alteration of Exocytosis-Associated Tumor Microenvironment.
AB  - The calcium-dependent activator protein for secretion 1 (CAPS1) regulates
      exocytosis of dense-core vesicles (DCVs) in neurons and neuroendocrine cells. The
      role of CAPS1 in cancer biology remains unknown. The purpose of this study was to
      investigate the role of CAPS1 in hepatocellular carcinoma (HCC). We determined
      the levels of CAPS1 in eight hepatoma cell lines and 141 HCC specimens. We
      evaluated the prognostic value of CAPS1 expression and its association with
      clinical parameters. We investigated the biological consequences of CAPS1
      overexpression in two hepatoma cell lines in vitro and in vivo. The results
      showed that loss of CAPS1 expression in HCC tissues was markedly correlated with
      aggressive tumor phenotypes, such as high-grade tumor node metastasis (TNM) stage
      (p = 0.003) and absence of tumor encapsulation (p = 0.016), and was associated
      with poor overall survival (p = 0.008) and high recurrence (p = 0.015). CAPS1
      overexpression inhibited cell proliferation and migration by changing the
      exocytosis-associated tumor microenvironment in hepatoma cells in vitro. The in
      vivo study showed that CAPS1 overexpression inhibited xenograft tumor growth.
      Together, these results identified a previously unrecognized tumor suppressor
      role for CAPS1 in HCC development.

PMID- 27690000
TI  - Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes.
AB  - To investigate whether ocular albinism type 1 (OA1) is differentially expressed
      in the skin of mice with different coat colors and to determine its correlation
      with coat color establishment in mouse, the expression patterns and tissue
      distribution characterization of OA1 in the skin of mice with different coat
      colors were qualitatively and quantitatively analyzed by real-time quantitative
      PCR (qRT-PCR), immunofluorescence staining and Western blot. The qRT-PCR analysis
      revealed that OA1 mRNA was expressed in all mice skin samples tested, with the
      highest expression level in brown skin, a moderate expression level in black skin
      and the lowest expression level in gray skin. Positive OA1 protein bands were
      also detected in all skin samples by Western blot analysis. The relative
      expression levels of OA1 protein in both black and brown skin were significantly
      higher than that in gray skin, but there was no significant difference between
      black and brown mice. Immunofluorescence assays revealed that OA1 was mainly
      expressed in the hair follicle matrix, the inner and outer root sheath in the
      skin tissues with different coat colors. To get further insight into the
      important role of OA1 in the melanocytes' pigmentation, we transfected the OA1
      into mouse melanocytes and then detected the relative expression levels of
      pigmentation-related gene. Simultaneously, we tested the melanin content of
      melanocytes. As a result, the overexpression of OA1 significantly increased the
      expression levels of microphthalmia-associated transcription factor (MITF),
      tyrosinase (TYR), tyrosinase-related protein 1 (TRP1) and premelanosome protein
      (PMEL). However, the tyrosinase-related protein 2 (TRP2) level was attenuated. By
      contrast, the level of glycoprotein non-metastatic melanoma protein b (GPNMB) was
      unaffected by OA1 overexpression. Furthermore, we observed a significant increase
      in melanin content in mouse melanocyte transfected OA1. Therefore, we propose
      that OA1 may participate in the formation of coat color by regulating the level
      of MITF and the number, size, motility and maturation of melanosome.

PMID- 27690001
TI  - Sodium Copper Chlorophyllin Immobilization onto Hippospongia communis Marine
      Demosponge Skeleton and Its Antibacterial Activity.
AB  - In this study, Hippospongia communis marine demosponge skeleton was used as an
      adsorbent for sodium copper chlorophyllin (SCC). Obtained results indicate the
      high sorption capacity of this biomaterial with respect to SCC. Batch experiments
      were performed under different conditions and kinetic and isotherms properties
      were investigated. Acidic pH and the addition of sodium chloride increased SCC
      adsorption. The experimental data were well described by a pseudo-second order
      kinetic model. Equilibrium adsorption isotherms were determined and the
      experimental data were analyzed using both Langmuir and Freundlich isotherms. The
      effectiveness of the process was confirmed by 13C Cross Polarization Magic Angle
      Spinning Nuclear Magnetic Resonance (13C CP/MAS NMR), Fourier transform infrared
      spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS) and
      thermogravimetric analysis (TG). This novel SCC-sponge-based functional hybrid
      material was found to exhibit antimicrobial activity against the gram-positive
      bacterium Staphylococcus aureus.

PMID- 27690002
TI  - Serum 25(OH) Vitamin D Levels in Polish Women during Pregnancies Complicated by
      Hypertensive Disorders and Gestational Diabetes.
AB  - BACKGROUND: An association between the level of vitamin D and the risk of
      pregnancy-related complications remains unclear. The aim of this study was to
      examine concentrations of 25(OH) vitamin D in Polish women with normal
      pregnancies and pregnancies complicated by gestational hypertension, preeclampsia
      or gestational diabetes mellitus (GDM). Moreover, we analyzed an association
      between maternal serum 25(OH)D and the risk of gestational hypertension,
      preeclampsia and GDM. MATERIAL AND METHODS: The study included 207 pregnant
      women, among them 171 with pregnancy-related complications: gestational
      hypertension (n = 45), preeclampsia (n = 23) or GDM (n = 103). The control group
      consisted of 36 women with normal pregnancies. Concentrations of serum 25(OH)D
      were measured at admission to the hospital prior to delivery Results: Patients
      with hypertension did not differ significantly from the controls in terms of
      their serum 25(OH)D concentrations (18.20 vs. 22.10 ng/mL, p = 0.15). Highly
      significant differences were found in 25(OH)D concentrations of women with
      preeclampsia and the controls (14.75 vs. 22.10 ng/mL, p = 0.0021). GDM was not
      associated with significant differences in 25(OH)D concentration. A low level of
      25(OH)D turned out to be associated with an increased risk of preeclampsia during
      pregnancy on both univariate and multivariate regression analysis, and was a
      significant predictor of this condition on ROC (receiver operating
      characteristic) analysis (AUC = 0.70, p < 0.01). CONCLUSIONS: 25(OH)D deficiency
      is common among pregnant Polish women. Low concentrations of 25(OH)D may play a
      role in the etiopathogenesis of preeclampsia. Routine assessment of the 25(OH)D
      level during pregnancy may be crucial for the identification of women at
      increased risk of preeclampsia.

PMID- 27690003
TI  - Decreased Expression of SRSF2 Splicing Factor Inhibits Apoptotic Pathways in
      Renal Cancer.
AB  - Serine and arginine rich splicing factor 2(SRSF2) belongs to the serine/arginine
      (SR)-rich family of proteins that regulate alternative splicing. Previous studies
      suggested that SRSF2 can contribute to carcinogenic processes. Clear cell renal
      cell carcinoma (ccRCC) is the most common subtype of kidney cancer, highly
      aggressive and difficult to treat, mainly due to resistance to apoptosis. In this
      study we hypothesized that SRSF2 contributes to the regulation of apoptosis in
      ccRCC. Using tissue samples obtained from ccRCC patients, as well as independent
      validation on The Cancer Genome Atlas (TCGA) data, we demonstrate for the first
      time that expression of SRSF2 is decreased in ccRCC tumours when compared to non
      tumorous control tissues. Furthermore, by employing a panel of ccRCC-derived cell
      lines with silenced SRSF2 expression and qPCR arrays we show that SRSF2
      contributes not only to splicing patterns but also to expression of multiple
      apoptotic genes, including new SRSF2 targets: DIABLO, BIRC5/survivin, TRAIL, BIM,
      MCL1, TNFRSF9, TNFRSF1B, CRADD, BCL2L2, BCL2A1, and TP53. We also identified a
      new splice variant of CFLAR, an inhibitor of caspase activity. These changes
      culminate in diminished caspase-9 activity and inhibition of apoptosis. In
      summary, we show for the first time that decreased expression of SRSF2 in ccRCC
      contributes to protection of cancer cells viability.

PMID- 27690004
TI  - Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes.
AB  - Red dragon fruit or red pitaya (Hylocereus polyrhizus) is the only edible fruit
      that contains betalains. The color of betalains ranges from red and violet to
      yellow in plants. Betalains may also serve as an important component of health
      promoting and disease-preventing functional food. Currently, the biosynthetic and
      regulatory pathways for betalain production remain to be fully deciphered. In
      this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based
      proteomic analyses were used to reveal the molecular mechanism of betalain
      biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively.
      A total of 1946 proteins were identified as the differentially expressed between
      the two samples, and 936 of them were significantly highly expressed at the red
      pulp stage of H. polyrhizus. RNA-seq and iTRAQ analyses showed that some
      transcripts and proteins were positively correlated; they belonged to
      "phenylpropanoid biosynthesis", "tyrosine metabolism", "flavonoid biosynthesis",
      "ascorbate and aldarate metabolism", "betalains biosynthesis" and "anthocyanin
      biosynthesis". In betalains biosynthesis pathway, several proteins/enzymes such
      as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA)
      dioxygenase extradiol-like protein were identified. The present study provides a
      new insight into the molecular mechanism of the betalain biosynthesis at the
      posttranscriptional level.

PMID- 27690005
TI  - Oral Supplementation with a Special Additive of Retinyl Palmitate and Alpha
      Tocopherol Reduces Growth Retardation in Young Pancreatic Duct Ligated Pigs Used
      as a Model for Children Suffering from Exocrine Pancreatic Insufficiency.
AB  - Pancreatic exocrine insufficiency (PEI) is a disease of diverse aetiology-e.g.,
      majority of patients suffering from cystic fibrosis (CF) show PEI congenitally.
      Malnutrition and malabsorption of nutrients impair growth and nutritional status.
      As reduced fat digestion leads to a deficiency of fat-soluble vitamins the
      supplementation is standard, but absorption is a critical point in PEI-patients.
      The pancreatic duct ligated (PL) pig is an established model for PEI in humans
      and has been proven to be a suitable model to compare different vitamin additives
      for supplementation. In a former study, PEI caused distinct growth retardation in
      young piglets, but did not affect growth in older ones. Our study hypothesised
      that this age-dependent effect is caused by exhausted body reserves of fat
      soluble vitamins and, therefore, extra supply reduces growth retardation. PEI was
      induced by PL at the age of seven (PL-7) or 16 weeks (PL-16). Controls (C)
      underwent a sham surgery. Some PL-7 pigs (PL-7 + Vit) were fed a special vitamin
      additive. PEI reduced the mean final body weight (kg) at 26 weeks of age
      significantly with lower effect in PL-16-pigs (C:117; PL-7:49.5; PL-7 + Vit:77.1;
      PL-16:96.4). Extra vitamin supply resulted in an increased growth and normalised
      serum concentration of alpha-tocopherol, underlining the importance of special
      supplementation in PEI-patients.

PMID- 27690006
TI  - iTRAQ-Based Proteomics Analysis of Serum Proteins in Wistar Rats Treated with
      Sodium Fluoride: Insight into the Potential Mechanism and Candidate Biomarkers of
      Fluorosis.
AB  - Fluorosis induced by exposure to high level fluoride is quite widespread in the
      world. The manifestations of fluorosis include dental mottling, bone damage, and
      impaired malfunction of soft tissues. However, the molecular mechanism of
      fluorosis has not been clarified until now. To explore the underlying mechanisms
      of fluorosis and screen out serum biomarkers, we carried out a quantitative
      proteomics study to identify differentially expressed serum proteins in Wistar
      rats treated with sodium fluoride (NaF) by using a proteomics approach of
      isobaric tagging for relative and absolute quantitation (iTRAQ). We fed Wistar
      rats drinking water that had 50, 150, and 250 mg/L of dissolved NaF for 24 weeks.
      For the experimental duration, each rat was given an examination of the lower
      incisors to check for the condition of dental fluorosis (DF). By the end of the
      treatment, fluoride ion concentration in serum and lower incisors were detected.
      The results showed that NaF treatment can induce rat fluorosis. By iTRAQ
      analysis, a total of 37 differentially expressed serum proteins were identified
      between NaF-treated and control rats. These proteins were further analyzed by
      bioinformatics, out of which two proteins were validated by enzyme-linked
      immunoadsorbent assays (ELISA). The major proteins were involved in complement
      and coagulation cascade, inflammatory response, complement activation, defense
      response, and wound response, suggesting that inflammation and immune reactions
      may play a key role in fluorosis pathogenesis. These proteins may contribute to
      the understanding of the mechanism of fluoride toxicity, and may serve as
      potential biomarkers for fluorosis.

PMID- 27690007
TI  - Stereoselective Blockage of Quinidine and Quinine in the hERG Channel and the
      Effect of Their Rescue Potency on Drug-Induced hERG Trafficking Defect.
AB  - Diastereoisomers of quinidine and quinine are used to treat arrhythmia and
      malaria, respectively. It has been reported that both drugs block the hERG (human
      ether-a-go-go-related gene) potassium channel which is essential for myocardium
      repolarization. Abnormality of repolarization increases risk of arrhythmia. The
      aim of our research is to study and compare the impacts of quinidine and quinine
      on hERG. Results show that both drugs block the hERG channel, with quinine 14
      fold less potent than quinidine. In addition, they presented distinct impacts on
      channel dynamics. The results imply their stereospecific block effect on the hERG
      channel. However, F656C-hERG reversed this stereoselectivity. The mutation
      decreases affinity of the two drugs with hERG, and quinine was more potent than
      quinidine in F656C-hERG blockage. These data suggest that F656 residue
      contributes to the stereoselective pocket for quinidine and quinine. Further
      study demonstrates that both drugs do not change hERG protein levels. In rescue
      experiments, we found that they exert no reverse effect on pentamidine- or
      desipramine-induced hERG trafficking defect, although quinidine has been reported
      to rescue trafficking-deficient pore mutation hERG G601S based on the interaction
      with F656. Our research demonstrated stereoselective effects of quinidine and
      quinine on the hERG channel, and this is the first study to explore their
      reversal potency on drug-induced hERG deficiency.

PMID- 27690008
TI  - Diatom Valve Three-Dimensional Representation: A New Imaging Method Based on
      Combined Microscopies.
AB  - The frustule of diatoms, unicellular microalgae, shows very interesting photonic
      features, generally related to its complicated and quasi-periodic micro- and nano
      structure. In order to simulate light propagation inside and through this natural
      structure, it is important to develop three-dimensional (3D) models for synthetic
      replica with high spatial resolution. In this paper, we present a new method that
      generates images of microscopic diatoms with high definition, by merging scanning
      electron microscopy and digital holography microscopy or atomic force microscopy
      data. Starting from two digital images, both acquired separately with standard
      characterization procedures, a high spatial resolution (Deltaz = lambda/20,
      Deltax = Deltay ? 100 nm, at least) 3D model of the object has been generated.
      Then, the two sets of data have been processed by matrix formalism, using an
      original mathematical algorithm implemented on a commercially available software.
      The developed methodology could be also of broad interest in the design and
      fabrication of micro-opto-electro-mechanical systems.

PMID- 27690009
TI  - CXCL12/CXCR4 Axis Regulates Aggrecanase Activation and Cartilage Degradation in a
      Post-Traumatic Osteoarthritis Rat Model.
AB  - We evaluated the role of the CXCL12/CXCR4 (C-X-C motif chemokine ligand 12/C-X-C
      chemokine receptor type 4) axis in aggrecanase-mediated cartilage degradation,
      and explored the underlying mechanism in a post-traumatic osteoarthritis rat
      model. Expression of CXCL12/CXCR4 and ADAMTS-5 was analyzed in the knees of
      osteoarthritic and non-arthritic rats using Western blot, ELISA,
      immunohistochemistry and immunofluorescence. Rodent studies were performed using
      Sprague-Dawley rats, with animals divided into three groups: Destabilization of
      the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), DMM/PBS-treated, and
      sham controls. Rats were sacrificed after eight weeks, and samples were collected
      for histology and immunohistochemistry analyses. IL-1-pretreated primary
      chondrocytes were cultured with untreated control, CXCL12a, siNC + CXCL12a, or
      siRNA CXCR4 + CXCL12a, and analyzed for expression of relevant markers and
      cellular pathways. Higher levels of CXCL12 were detected in the knee fluid of
      osteoarthritic subjects, with strong staining for CXCR4 in chondrocytes and
      CXCL12 in synoviocytes together with enhanced expression of ADAMTS-5. DMM/AMD3100
      treated rats showed a significantly reduced immunological response, with minimal
      evidence of pathology in both histological and immunohistochemical analyses.
      Treatment with CXCL12a increased the expression of ACAN, RUNX-2, and ADAMTS-4/5
      in IL-1-pretreated primary chondrocytes, together with a decrease in the
      expression of SOX-9. Molecular analyses revealed strong induction of NF-kappaB
      activation, along with phosphorylation of MAPKs, and activation of canonical
      Wnt/beta-catenin signaling. In conclusion, inhibition of SDF-1alpha/CXCR4
      signaling axis was able to inhibit aggrecanase expression and lessen cartilage
      degeneration in post-traumatic osteoarthritis rats.

PMID- 27690010
TI  - Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate
      mTORC1.
AB  - The mammalian target of rapamycin (mTOR) is the central regulator of mammalian
      cell growth, and is essential for the formation of two structurally and
      functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple
      cues such as nutrients, energy status, growth factors and hormones to control
      cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of
      the key environmental stimuli, amino acids (AAs), especially leucine, glutamine
      and arginine, play a crucial role in mTORC1 activation, but where and how AAs are
      sensed and signal to mTORC1 are not fully understood. Classically, AAs activate
      mTORC1 by Rag GTPases which recruit mTORC1 to lysosomes, where AA signaling
      initiates. Plasma membrane transceptor L amino acid transporter 1 (LAT1)-4F2hc
      has dual transporter-receptor function that can sense extracellular AA
      availability upstream of mTORC1. The lysosomal AA sensors (PAT1 and SLC38A9) and
      cytoplasmic AA sensors (LRS, Sestrin2 and CASTOR1) also participate in regulating
      mTORC1 activation. Importantly, AAs can be sensed by plasma membrane receptors,
      like G protein-coupled receptor (GPCR) T1R1/T1R3, and regulate mTORC1 without
      being transported into the cells. Furthermore, AA-dependent mTORC1 activation
      also initiates within Golgi, which is regulated by Golgi-localized AA transporter
      PAT4. This review provides an overview of the research progress of the AA sensing
      mechanisms that regulate mTORC1 activity.

PMID- 27690012
TI  - EpCAM Expression in Lymph Node and Bone Metastases of Prostate Carcinoma: A Pilot
      Study.
AB  - There is an urgent need for new imaging modalities in prostate carcinoma staging.
      A non-invasive modality that can assess lymph node and bone metastases
      simultaneously is preferred. Epithelial cell adhesion molecule (EpCAM) is a
      membranous protein of interest as an imaging target since it is overexpressed in
      prostatic carcinoma compared with benign prostate epithelium and compared with
      stroma. However, EpCAM expression in lymph node metastases is sparsely available
      in the literature and EpCAM expression in bone metastases is yet unknown. The
      current study evaluates the expression of EpCAM in prostate carcinoma lymph
      nodes, in matched normal lymph nodes, in prostate carcinoma bone metastases, and
      in normal bone by immunohistochemistry. EpCAM was expressed in 100% of lymph node
      metastases (21 out of 21), in 0% of normal lymph nodes (0 out of 21), in 95% of
      bone metastases (19 out of 20), and in 0% of normal bone (0 out of 14). Based on
      these results, EpCAM may be a feasible imaging target in prostate carcinoma lymph
      node and bone metastases. Prospective clinical trials are needed to confirm
      current results. Preoperative visualization of prostate carcinoma metastases will
      improve disease staging and will prevent unnecessary invasive surgery.

PMID- 27690011
TI  - Aquaporin-4: A Potential Therapeutic Target for Cerebral Edema.
AB  - Aquaporin-4 (AQP4) is a family member of water-channel proteins and is dominantly
      expressed in the foot process of glial cells surrounding capillaries. The
      predominant expression at the boundaries between cerebral parenchyma and major
      fluid compartments suggests the function of aquaporin-4 in water transfer into
      and out of the brain parenchyma. Accumulating evidences have suggested that the
      dysregulation of aquaporin-4 relates to the brain edema resulting from a variety
      of neuro-disorders, such as ischemic or hemorrhagic stroke, trauma, etc. During
      edema formation in the brain, aquaporin-4 has been shown to contribute to the
      astrocytic swelling, while in the resolution phase, it has been seen to
      facilitate the reabsorption of extracellular fluid. In addition, aquaporin-4
      deficient mice are protected from cytotoxic edema produced by water intoxication
      and brain ischemia. However, aquaporin-4 deletion exacerbates vasogenic edema in
      the brain of different pathological disorders. Recently, our published data
      showed that the upregulation of aquaporin-4 in astrocytes probably contributes to
      the transition from cytotoxic edema to vasogenic edema. In this review, apart
      from the traditional knowledge, we also introduce our latest findings about the
      effects of mesenchymal stem cells (MSCs) and microRNA-29b on aquaporin-4, which
      could provide powerful intervention tools targeting aquaporin-4.

PMID- 27690013
TI  - Time in Redox Adaptation Processes: From Evolution to Hormesis.
AB  - Life on Earth has to adapt to the ever changing environment. For example, due to
      introduction of oxygen in the atmosphere, an antioxidant network evolved to cope
      with the exposure to oxygen. The adaptive mechanisms of the antioxidant network,
      specifically the glutathione (GSH) system, are reviewed with a special focus on
      the time. The quickest adaptive response to oxidative stress is direct enzyme
      modification, increasing the GSH levels or activating the GSH-dependent
      protective enzymes. After several hours, a hormetic response is seen at the
      transcriptional level by up-regulating Nrf2-mediated expression of enzymes
      involved in GSH synthesis. In the long run, adaptations occur at the epigenetic
      and genomic level; for example, the ability to synthesize GSH by phototrophic
      bacteria. Apparently, in an adaptive hormetic response not only the dose or the
      compound, but also time, should be considered. This is essential for targeted
      interventions aimed to prevent diseases by successfully coping with changes in
      the environment e.g., oxidative stress.

PMID- 27690015
TI  - GSPE Inhibits HMGB1 Release, Attenuating Renal IR-Induced Acute Renal Injury and
      Chronic Renal Fibrosis.
AB  - Grape seed proanthocyanindin extract (GSPE) is a polyphenolic bioflavonoid
      derived from grape seeds and has been widely studied for its potent antioxidant,
      anti-inflammatory and antitumor activities. HMGB1 is a newly discovered danger
      associated molecular pattern (DAMP) that has potent proinflammatory effects once
      released by necrotic cells. However, the effect of GSPE on the HMGB1, and the
      relationship of those two with acute kidney injury and chronic kidney fibrosis
      are unknown. This study aimed to investigate the impact of GSPE on acute kidney
      injury and chronic fibrosis. C57bl/6 mice were subjected to bilateral
      ischemia/reperfusion (I/R) and unilateral I/R with or without GSPE
      administration. After bilateral I/R, mice administered GSPE had a marked
      improvement in renal function (BUN and Cr), decreased pathological damage and
      reduced inflammation. In unilateral I/R, mice subjected GSPE showed reduced
      tubulointerstitial fibrosis and decreased inflammatory reaction. The
      renoprotection of GSPE on both models was associated with the inhibition of HMGB1
      nucleocytoplasmic shuttling and release, which can amplify the inflammation
      through binding to its downstream receptor TLR4 and facilitated P65
      transcription. Thus, we have reason to believe that GSPE could be a good
      alternative therapy for the prevention and treatment of IR-induced renal injury
      and fibrosis in clinical practice.

PMID- 27690017
TI  - Extracellular Self-DNA (esDNA), but Not Heterologous Plant or Insect DNA (etDNA),
      Induces Plasma Membrane Depolarization and Calcium Signaling in Lima Bean
      (Phaseolus lunatus) and Maize (Zea mays).
AB  - Extracellular self-DNA (esDNA) is produced during cell and tissue damage or
      degradation and has been shown to induce significant responses in several
      organisms, including plants. While the inhibitory effects of esDNA have been
      shown in conspecific individuals, little is known on the early events involved
      upon plant esDNA perception. We used electrophysiology and confocal laser
      scanning microscopy calcium localization to evaluate the plasma membrane
      potential (Vm) variations and the intracellular calcium fluxes, respectively, in
      Lima bean (Phaseolus lunatus) and maize (Zea mays) plants exposed to esDNA and
      extracellular heterologous DNA (etDNA) and to etDNA from Spodoptera littoralis
      larvae and oral secretions. In both species, esDNA induced a significant Vm
      depolarization and an increased flux of calcium, whereas etDNA was unable to
      exert any of these early signaling events. These findings confirm the specificity
      of esDNA to induce plant cell responses and to trigger early signaling events
      that eventually lead to plant response to damage.

PMID- 27690014
TI  - New Treatment Strategies for Alcohol-Induced Heart Damage.
AB  - High-dose alcohol misuse induces multiple noxious cardiac effects, including
      myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular
      contraction and ventricle enlargement. These effects produce diastolic and
      systolic ventricular dysfunction leading to congestive heart failure, arrhythmias
      and an increased death rate. There are multiple, dose-dependent, synchronic and
      synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane
      permeability and composition, interferes with receptors and intracellular
      transients, induces oxidative, metabolic and energy damage, decreases protein
      synthesis, excitation-contraction coupling and increases cell apoptosis. In
      addition, ethanol decreases myocyte protective and repair mechanisms and their
      regeneration. Although there are diverse different strategies to directly target
      alcohol-induced heart damage, they are partially effective, and can only be used
      as support medication in a multidisciplinary approach. Alcohol abstinence is the
      preferred goal, but control drinking is useful in alcohol-addicted subjects not
      able to abstain. Correction of nutrition, ionic and vitamin deficiencies and
      control of alcohol-related systemic organ damage are compulsory. Recently,
      several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK
      inhibitors) and new cardiomyokines such as FGF21 have been described to regulate
      cardiac plasticity and decrease cardiac damage, improving cardiac repair
      mechanisms, and they are promising agents in this field. New potential
      therapeutic targets aim to control oxidative damage, myocyte hypertrophy,
      interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may
      improve myocyte regeneration. However, these strategies are not yet approved for
      clinical use.

PMID- 27690016
TI  - Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and
      Its Molecular Link to Patient Osteoporosis.
AB  - Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing
      disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and
      osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD
      is still unclear because of a lack of human cell lines and animal models. Here,
      we study 106 clinical characteristics and gene expression changes from 118
      patients, the largest cohort of CD in a single-center. RNA deep sequencing is
      used to examine genotypic changes in nine paired female ACTH-secreting pituitary
      adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel
      analysis linking disease clinical characteristics and whole transcriptomic
      changes, using Pearson Correlation Coefficient to discover a molecular network
      mechanism. We report that osteoporosis is distinguished from the phenotype and
      genotype analysis. A cluster of genes involved in osteoporosis is identified
      using Pearson correlation coefficient analysis. Most of the genes are reported in
      the bone related literature, confirming the feasibility of phenotype-genotype
      association analysis, which could be used in the analysis of almost all diseases.
      Secreted phosphoprotein 1 (SPP1), collagen type I alpha 1 chain (COL1A1), 5'
      nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1
      (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis
      in CD patients. Our discoveries provide a molecular link for osteoporosis in CD
      patients, and may open new potential avenues for osteoporosis intervention and
      treatment.

PMID- 27690018
TI  - Essential Roles of Natural Products and Gaseous Mediators on Neuronal Cell Death
      or Survival.
AB  - Although precise cellular and molecular mechanisms underlying neurodegeneration
      still remain enigmatic, key factors associated with degenerative disorders, such
      as glutamate toxicity and oxidative stress, have been recently identified.
      Accordingly, there has been growing interest in examining the effects of
      exogenous and endogenous molecules on neuroprotection and neurodegeneration. In
      this paper, we review recent studies on neuroprotective and/or neurodegenerative
      effects of natural products, such as caffeic acid and chlorogenic acid, and
      gaseous mediators, including hydrogen sulfide and nitric oxide. Furthermore,
      possible molecular mechanisms of these molecules in relation to glutamate signals
      are discussed. Insight into the pathophysiological role of these molecules will
      make progress in our understanding of molecular mechanisms underlying
      neurodegenerative diseases, and is expected to lead to potential therapeutic
      approaches.

PMID- 27690019
TI  - Longitudinal Claudin Gene Expression Analyses in Canine Mammary Tissues and
      Thereof Derived Primary Cultures and Cell Lines.
AB  - Human and canine mammary tumours show partial claudin expression deregulations.
      Further, claudins have been used for directed therapeutic approaches. However,
      the development of claudin targeting approaches requires stable claudin
      expressing cell lines. This study reports the establishment and characterisation
      of canine mammary tissue derived cell lines, analysing longitudinally the claudin
      1, -3, -4 and -7 expressions in original tissue samples, primary cultures and
      developed cell lines. Primary cultures were derived from 17 canine mammary
      tissues: healthy, lobular hyperplasia, simple adenoma, complex adenoma, simple
      tubular carcinoma, complex carcinoma, carcinoma arising in a benign mixed tumour
      and benign mixed tissue. Cultivation was performed, if possible, until passage
      30. Claudin mRNA and protein expressions were analysed by PCR, QuantiGene Plex
      Assay, immunocytochemistry and immunofluorescence. Further, cytokeratin
      expression was analysed immunocytochemically. Cultivation resulted in 11
      established cell lines, eight showing epithelial character. In five of the early
      passages the claudin expressions decreased compared to the original tissues. In
      general, claudin expressions were diminished during cultivation. Three cell lines
      kept longitudinally claudin, as well as epithelial marker expressions,
      representing valuable tools for the development of claudin targeted anti-tumour
      therapies.

PMID- 27690020
TI  - Fruit Antioxidants during Vinegar Processing: Changes in Content and in Vitro Bio
      Accessibility.
AB  - BACKGROUND: Vinegars based on fruit juices could conserve part of the health
      associated compounds present in the fruits. However, in general very limited
      knowledge exists on the consequences of vinegar-making on different antioxidant
      compounds from fruit. In this study vinegars derived from apple and grape are
      studied. METHODS: A number of steps, starting from the fermentation of the fruit
      juices to the formation of the final vinegars, were studied from an industrial
      vinegar process. The effect of each of the vinegar processing steps on content of
      antioxidants, phenolic compounds and flavonoids was studied, by spectroscopic
      methods and by high-performance liquid chromatography (HPLC). RESULTS: The major
      observation was that spectrophotometric methods indicate a strong loss of
      antioxidant phenolic compounds during the transition from fruit wine to fruit
      vinegar. A targeted HPLC analysis indicates that metabolites such as gallic acid
      are lost in later stages of the vinegar process. CONCLUSION: The major conclusion
      of this work is that major changes occur in phenolic compounds during vinegar
      making. An untargeted metabolite analysis should be used to reveal these changes
      in more detail. In addition, the effect of vinegar processing on bio
      accessibility of phenolic compounds was investigated by mimicking the digestive
      tract in an in vitro set up. This study is meant to provide insight into the
      potential of vinegar as a source of health-related compounds from fruit.

PMID- 27690021
TI  - ns-MUs Time-Resolved Step-Scan FTIR of ba3 Oxidoreductase from Thermus
      thermophilus: Protonic Connectivity of w941-w946-w927.
AB  - Time-resolved step-scan FTIR spectroscopy has been employed to probe the dynamics
      of the ba3 oxidoreductase from Thermus thermophilus in the ns-MUs time range and
      in the pH/pD 6-9 range. The data revealed a pH/pD sensitivity of the D372 residue
      and of the ring-A propionate of heme a3. Based on the observed transient changes
      a model in which the protonic connectivity of w941-w946-927 to the D372 and the
      ring-A propionate of heme a3 is described.

PMID- 27690022
TI  - Cinnamide Derivatives as Mammalian Arginase Inhibitors: Synthesis, Biological
      Evaluation and Molecular Docking.
AB  - Arginases are enzymes that are involved in many human diseases and have been
      targeted for new treatments. Here a series of cinnamides was designed,
      synthesized and evaluated in vitro and in silico for their inhibitory activity
      against mammalian arginase. Using a microassay on purified liver bovine arginase
      (b-ARG I), (E)-N-(2-phenylethyl)-3,4-dihydroxycinnamide, also named caffeic acid
      phenylamide (CAPA), was shown to be slightly more active than our natural
      reference inhibitor, chlorogenic acid (IC50 = 6.9 +/- 1.3 and 10.6 +/- 1.6 uM,
      respectively) but it remained less active that the synthetic reference inhibitor
      Nomega-hydroxy-nor-l-arginine nor-NOHA (IC50 = 1.7 +/- 0.2 uM). Enzyme kinetic
      studies showed that CAPA was a competitive inhibitor of arginase with Ki = 5.5 +/
      1 uM. Whereas the activity of nor-NOHA was retained (IC50 = 5.7 +/- 0.6 uM)
      using a human recombinant arginase I (h-ARG I), CAPA showed poorer activity (IC50
      = 60.3 +/- 7.8 uM). However, our study revealed that the cinnamoyl moiety and
      catechol function were important for inhibitory activity. Docking results on h
      ARG I demonstrated that the caffeoyl moiety could penetrate into the active-site
      pocket of the enzyme, and the catechol function might interact with the cofactor
      Mn2+ and several crucial amino acid residues involved in the hydrolysis mechanism
      of arginase. The results of this study suggest that 3,4-dihydroxycinnamides are
      worth being considered as potential mammalian arginase inhibitors, and could be
      useful for further research on the development of new arginase inhibitors.

PMID- 27690023
TI  - Gait Phase Recognition for Lower-Limb Exoskeleton with Only Joint Angular
      Sensors.
AB  - Gait phase is widely used for gait trajectory generation, gait control and gait
      evaluation on lower-limb exoskeletons. So far, a variety of methods have been
      developed to identify the gait phase for lower-limb exoskeletons. Angular sensors
      on lower-limb exoskeletons are essential for joint closed-loop controlling;
      however, other types of sensors, such as plantar pressure, attitude or inertial
      measurement unit, are not indispensable.Therefore, to make full use of existing
      sensors, we propose a novel gait phase recognition method for lower-limb
      exoskeletons using only joint angular sensors. The method consists of two
      procedures. Firstly, the gait deviation distances during walking are calculated
      and classified by Fisher's linear discriminant method, and one gait cycle is
      divided into eight gait phases. The validity of the classification results is
      also verified based on large gait samples. Secondly, we build a gait phase
      recognition model based on multilayer perceptron and train it with the phase
      labeled gait data. The experimental result of cross-validation shows that the
      model has a 94.45% average correct rate of set (CRS) and an 87.22% average
      correct rate of phase (CRP) on the testing set, and it can predict the gait phase
      accurately. The novel method avoids installing additional sensors on the
      exoskeleton or human body and simplifies the sensory system of the lower-limb
      exoskeleton.

PMID- 27690024
TI  - Infrared LED Enhanced Spectroscopic CdZnTe Detector Working under High Fluxes of
      X-rays.
AB  - This paper describes an application of infrared light-induced de-polarization
      applied on a polarized CdZnTe detector working under high radiation fluxes. We
      newly demonstrate the influence of a high flux of X-rays and simultaneous 1200-nm
      LED illumination on the spectroscopic properties of a CdZnTe detector. CdZnTe
      detectors operating under high radiation fluxes usually suffer from the
      polarization effect, which occurs due to a screening of the internal electric
      field by a positive space charge caused by photogenerated holes trapped at a deep
      level. Polarization results in the degradation of detector charge collection
      efficiency. We studied the spectroscopic behavior of CdZnTe under various X-ray
      fluxes ranging between 5 * 10 5 and 8 * 10 6 photons per mm 2 per second. It was
      observed that polarization occurs at an X-ray flux higher than 3 * 10 6 mm - 2 .s
      - 1 . Using simultaneous illumination of the detector by a de-polarizing LED at
      1200 nm, it was possible to recover X-ray spectra originally deformed by the
      polarization effect.

PMID- 27690025
TI  - Analysis of Abnormal Intra-QRS Potentials in Signal-Averaged Electrocardiograms
      Using a Radial Basis Function Neural Network.
AB  - Abnormal intra-QRS potentials (AIQPs) are commonly observed in patients at high
      risk for ventricular tachycardia. We present a method for approximating a
      measured QRS complex using a non-linear neural network with all radial basis
      functions having the same smoothness. We extracted the high frequency, but low
      amplitude intra-QRS potentials using the approximation error to identify possible
      ventricular tachycardia. With a specified number of neurons, we performed an
      orthogonal least squares algorithm to determine the center of each Gaussian
      radial basis function. We found that the AIQP estimation error arising from part
      of the normal QRS complex could cause clinicians to misjudge patients with
      ventricular tachycardia. Our results also show that it is possible to correct
      this misjudgment by combining multiple AIQP parameters estimated using various
      spread parameters and numbers of neurons. Clinical trials demonstrate that higher
      AIQP-to-QRS ratios in the X, Y and Z leads are visible in patients with
      ventricular tachycardia than in normal subjects. A linear combination of 60 AIQP
      to-QRS ratios can achieve 100% specificity, 90% sensitivity, and 95.8% total
      prediction accuracy for diagnosing ventricular tachycardia.

PMID- 27690026
TI  - Inferring Human Activity Recognition with Ambient Sound on Wireless Sensor Nodes.
AB  - A wireless sensor network that consists of nodes with a sound sensor can be used
      to obtain context awareness in home environments. However, the limited processing
      power of wireless nodes offers a challenge when extracting features from the
      signal, and subsequently, classifying the source. Although multiple papers can be
      found on different methods of sound classification, none of these are aimed at
      limited hardware or take the efficiency of the algorithms into account. In this
      paper, we compare and evaluate several classification methods on a real sensor
      platform using different feature types and classifiers, in order to find an
      approach that results in a good classifier that can run on limited hardware. To
      be as realistic as possible, we trained our classifiers using sound waves from
      many different sources. We conclude that despite the fact that the classifiers
      are often of low quality due to the highly restricted hardware resources,
      sufficient performance can be achieved when (1) the window length for our
      classifiers is increased, and (2) if we apply a two-step approach that uses a
      refined classification after a global classification has been performed.

PMID- 27690027
TI  - Effective Waterline Detection of Unmanned Surface Vehicles Based on Optical
      Images.
AB  - Real-time and accurate detection of the sailing or water area will help realize
      unmanned surface vehicle (USV) systems. Although there are some methods for using
      optical images in USV-oriented environmental modeling, both the robustness and
      precision of these published waterline detection methods are comparatively low
      for a real USV system moving in a complicated environment. This paper proposes an
      efficient waterline detection method based on structure extraction and texture
      analysis with respect to optical images and presents a practical application to a
      USV system for validation. First, the basic principles of local binary patterns
      (LBPs) and gray level co-occurrence matrix (GLCM) were analyzed, and their
      advantages were integrated to calculate the texture information of river images.
      Then, structure extraction was introduced to preprocess the original river images
      so that the textures resulting from USV motion, wind, and illumination are
      removed. In the practical application, the waterlines of many images captured by
      the USV system moving along an inland river were detected with the proposed
      method, and the results were compared with those of edge detection and super
      pixel segmentation. The experimental results showed that the proposed algorithm
      is effective and robust. The average error of the proposed method was 1.84
      pixels, and the mean square deviation was 4.57 pixels.

PMID- 27690028
TI  - Enhanced RGB-D Mapping Method for Detailed 3D Indoor and Outdoor Modeling.
AB  - RGB-D sensors (sensors with RGB camera and Depth camera) are novel sensing
      systems that capture RGB images along with pixel-wise depth information. Although
      they are widely used in various applications, RGB-D sensors have significant
      drawbacks including limited measurement ranges (e.g., within 3 m) and errors in
      depth measurement increase with distance from the sensor with respect to 3D dense
      mapping. In this paper, we present a novel approach to geometrically integrate
      the depth scene and RGB scene to enlarge the measurement distance of RGB-D
      sensors and enrich the details of model generated from depth images. First,
      precise calibration for RGB-D Sensors is introduced. In addition to the
      calibration of internal and external parameters for both, IR camera and RGB
      camera, the relative pose between RGB camera and IR camera is also calibrated.
      Second, to ensure poses accuracy of RGB images, a refined false features matches
      rejection method is introduced by combining the depth information and initial
      camera poses between frames of the RGB-D sensor. Then, a global optimization
      model is used to improve the accuracy of the camera pose, decreasing the
      inconsistencies between the depth frames in advance. In order to eliminate the
      geometric inconsistencies between RGB scene and depth scene, the scale ambiguity
      problem encountered during the pose estimation with RGB image sequences can be
      resolved by integrating the depth and visual information and a robust rigid
      transformation recovery method is developed to register RGB scene to depth scene.
      The benefit of the proposed joint optimization method is firstly evaluated with
      the publicly available benchmark datasets collected with Kinect. Then, the
      proposed method is examined by tests with two sets of datasets collected in both
      outside and inside environments. The experimental results demonstrate the
      feasibility and robustness of the proposed method.

PMID- 27690029
TI  - The Design and Analysis of Split Row-Column Addressing Array for 2-D Transducer.
AB  - For 3-D ultrasound imaging, the row-column addressing (RCA) with 2N connections
      for an N * N 2-D array makes the fabrication and interconnection simpler than the
      fully addressing with N2 connections. However, RCA degrades the image quality
      because of defocusing in signal channel direction in the transmit event. To solve
      this problem, a split row-column addressing scheme (SRCA) is proposed in this
      paper. Rather than connecting all the elements in the signal channel direction
      together, this scheme divides the elements in the signal channel direction into
      several disconnected blocks, thus enables focusing beam access in both signal
      channel and switch channel directions. Selecting an appropriate split scheme is
      the key for SRCA to maintaining a reasonable tradeoff between the image quality
      and the number of connections. Various split schemes for a 32 * 32 array are
      fully investigated with point spread function (PSF) analysis and imaging
      simulation. The result shows the split scheme with five blocks (4, 6, 12, 6, and
      4 elements of each block) can provide similar image quality to fully addressing.
      The splitting schemes for different array sizes from 16 * 16 to 96 * 96 are also
      discussed.

PMID- 27690030
TI  - Adaptive Connectivity Restoration from Node Failure(s) in Wireless Sensor
      Networks.
AB  - Recently, there is a growing interest in the applications of wireless sensor
      networks (WSNs). A set of sensor nodes is deployed in order to collectively
      survey an area of interest and/or perform specific surveillance tasks in some of
      the applications, such as battlefield reconnaissance. Due to the harsh deployment
      environments and limited energy supply, nodes may fail, which impacts the
      connectivity of the whole network. Since a single node failure (cut-vertex) will
      destroy the connectivity and divide the network into disjoint blocks, most of the
      existing studies focus on the problem of single node failure. However, the
      failure of multiple nodes would be a disaster to the whole network and must be
      repaired effectively. Only few studies are proposed to handle the problem of
      multiple cut-vertex failures, which is a special case of multiple node failures.
      Therefore, this paper proposes a comprehensive solution to address the problems
      of node failure (single and multiple). Collaborative Single Node Failure
      Restoration algorithm (CSFR) is presented to solve the problem of single node
      failure only with cooperative communication, but CSFR-M, which is the extension
      of CSFR, handles the single node failure problem more effectively with node
      motion. Moreover, Collaborative Connectivity Restoration Algorithm (CCRA) is
      proposed on the basis of cooperative communication and node maneuverability to
      restore network connectivity after multiple nodes fail. CSFR-M and CCRA are
      reactive methods that initiate the connectivity restoration after detecting the
      node failure(s). In order to further minimize the energy dissipation, CCRA opts
      to simplify the recovery process by gridding. Moreover, the distance that an
      individual node needs to travel during recovery is reduced by choosing the
      nearest suitable candidates. Finally, extensive simulations validate the
      performance of CSFR, CSFR-M and CCRA.

PMID- 27690031
TI  - Home Automation System Based on Intelligent Transducer Enablers.
AB  - This paper presents a novel home automation system named HASITE (Home Automation
      System based on Intelligent Transducer Enablers), which has been specifically
      designed to identify and configure transducers easily and quickly. These features
      are especially useful in situations where many transducers are deployed, since
      their setup becomes a cumbersome task that consumes a significant amount of time
      and human resources. HASITE simplifies the deployment of a home automation system
      by using wireless networks and both self-configuration and self-registration
      protocols. Thanks to the application of these three elements, HASITE is able to
      add new transducers by just powering them up. According to the tests performed in
      different realistic scenarios, a transducer is ready to be used in less than 13
      s. Moreover, all HASITE functionalities can be accessed through an API, which
      also allows for the integration of third-party systems. As an example, an Android
      application based on the API is presented. Remote users can use it to interact
      with transducers by just using a regular smartphone or a tablet.

PMID- 27690032
TI  - Characterization of Screen-Printed Organic Electrochemical Transistors to Detect
      Cations of Different Sizes.
AB  - A novel screen-printing fabrication method was used to prepare organic
      electrochemical transistors (OECTs) based on poly(3,4-ethylenedioxythiophene)
      doped with polysterene sulfonate (PEDOT:PSS). Initially, three types of these
      screen-printed OECTs with a different channel and gate areas ratio were compared
      in terms of output characteristics, transfer characteristics, and current
      modulation in a phosphate buffered saline (PBS) solution. Results confirm that
      transistors with a gate electrode larger than the channel exhibit higher
      modulation. OECTs with this geometry were therefore chosen to investigate their
      ion-sensitive properties in aqueous solutions of cations of different sizes
      (sodium and rhodamine B). The effect of the gate electrode was additionally
      studied by comparing these all-PEDOT:PSS transistors with OECTs with the same
      geometry but with a non-polarizable metal gate (Ag). The operation of the all
      PEDOT:PSS OECTs yields a response that is not dependent on a Na+ or rhodamine
      concentration. The weak modulation of these transistors can be explained assuming
      that PEDOT:PSS behaves like a supercapacitor. In contrast, the operation of Ag
      Gate OECTs yields a response that is dependent on ion concentration due to the
      redox reaction taking place at the gate electrode with Cl- counter-ions. This
      indicates that, for cation detection, the response is maximized in OECTs with non
      polarizable gate electrodes.

PMID- 27690033
TI  - The Usability of a Pressure-Indicating Film to Measure the Teat Load Caused by a
      Collapsing Liner.
AB  - Prevention of damage to the teat and mastitis requires determination of the teat
      load caused by a collapsing liner. The aim of this study was to test a pressure
      indicating film designed to measure the pressure between a collapsing liner and
      artificial teats. The Ultra Super Low and the Extreme Low pressure-indicating
      films were tested on two types of artificial teat. The experiments were performed
      with a conventional milking cluster equipped with round silicone liners. For each
      teat and film type, 30 repetitions were performed. Each repetition was performed
      with a new piece of film. Kruskal-Wallis tests were performed to detect
      differences between the pressure values for the different teats. The area of
      regions where pressure-indication color developed was calculated to determine the
      most suitable film type. Both film types measured the pressure applied to both
      artificial teats by the teat cup liner. Thus, the pressure-indicating films can
      be used to measure the pressure between a collapsing liner and an artificial
      teat. Based on the results of the present investigation, a pressure-indicating
      film with the measurement ranges of both film types combined would be an optimal
      tool to measure the overall pressure between an artificial teat and a collapsing
      liner.

PMID- 27690034
TI  - Broadband Cooperative Spectrum Sensing Based on Distributed Modulated Wideband
      Converter.
AB  - The modulated wideband converter (MWC) is a kind of sub-Nyquist sampling system
      which is developed from compressed sensing theory. It accomplishes highly
      accurate broadband sparse signal recovery by multichannel sub-Nyquist sampling
      sequences. However, when the number of sparse sub-bands becomes large, the amount
      of sampling channels increases proportionally. Besides, it is very hard to adjust
      the number of sampling channels when the sparsity changes, because its
      undersampling board is designed by a given sparsity. Such hardware cost and
      inconvenience are unacceptable in practical applications. This paper proposes a
      distributed modulated wideband converter (DMWC) scheme innovatively, which
      regards one sensor node as one sampling channel and combines MWC technology with
      a broadband cooperative spectrum sensing network perfectly. Being different from
      the MWC scheme, DMWC takes phase shift and transmission loss into account in the
      input terminal, which are unavoidable in practical application. Our scheme is not
      only able to recover the support of broadband sparse signals quickly and
      accurately, but also reduces the hardware cost of the single node drastically.
      Theoretical analysis and numerical simulations show that phase shift has no
      influence on the recovery of frequency support, but transmission loss degrades
      the recovery performance to a different extent. Nevertheless, we can increase the
      amount of cooperative nodes and select satisfactory nodes by a different
      transmission distance to improve the recovery performance. Furthermore, we can
      adjust the amount of cooperative nodes flexibly when the sparsity changes. It
      indicates DMWC is extremely effective in the broadband cooperative spectrum
      sensing network.

PMID- 27690035
TI  - Temporal Data-Driven Sleep Scheduling and Spatial Data-Driven Anomaly Detection
      for Clustered Wireless Sensor Networks.
AB  - The spatial-temporal correlation is an important feature of sensor data in
      wireless sensor networks (WSNs). Most of the existing works based on the spatial
      temporal correlation can be divided into two parts: redundancy reduction and
      anomaly detection. These two parts are pursued separately in existing works. In
      this work, the combination of temporal data-driven sleep scheduling (TDSS) and
      spatial data-driven anomaly detection is proposed, where TDSS can reduce data
      redundancy. The TDSS model is inspired by transmission control protocol (TCP)
      congestion control. Based on long and linear cluster structure in the tunnel
      monitoring system, cooperative TDSS and spatial data-driven anomaly detection are
      then proposed. To realize synchronous acquisition in the same ring for analyzing
      the situation of every ring, TDSS is implemented in a cooperative way in the
      cluster. To keep the precision of sensor data, spatial data-driven anomaly
      detection based on the spatial correlation and Kriging method is realized to
      generate an anomaly indicator. The experiment results show that cooperative TDSS
      can realize non-uniform sensing effectively to reduce the energy consumption. In
      addition, spatial data-driven anomaly detection is quite significant for
      maintaining and improving the precision of sensor data.

PMID- 27690036
TI  - Multi-Frequency Target Detection Techniques for DVB-T Based Passive Radar
      Sensors.
AB  - This paper investigates the possibility to improve target detection capability in
      a DVB-T- based passive radar sensor by jointly exploiting multiple digital
      television channels broadcast by the same transmitter of opportunity. Based on
      the remarkable results obtained by such a multi-frequency approach using other
      signals of opportunity (i.e., FM radio broadcast transmissions), we propose
      appropriate modifications to the previously devised signal processing techniques
      for them to be effective in the newly considered scenarios. The resulting
      processing schemes are extensively applied against experimental DVB-T-based
      passive radar data pertaining to different surveillance applications. The
      obtained results clearly show the effectiveness of the proposed multi-frequency
      approaches and demonstrate their suitability for application in the considered
      scenarios.

PMID- 27690037
TI  - Phosphor-Doped Thermal Barrier Coatings Deposited by Air Plasma Spray for In
      Depth Temperature Sensing.
AB  - Yttria-stabilized zirconia (YSZ)-based thermal barrier coating (TBC) has been
      integrated with thermographic phosphors through air plasma spray (APS) for in
      depth; non-contact temperature sensing. This coating consisted of a thin layer of
      Dy-doped YSZ (about 40 um) on the bottom and a regular YSZ layer with a thickness
      up to 300 um on top. A measurement system has been established; which included a
      portable; low-cost diode laser (405 nm); a photo-multiplier tube (PMT) and the
      related optics. Coating samples with different topcoat thickness were calibrated
      in a high-temperature furnace from room temperature to around 900  degrees C. The
      results convincingly showed that the current sensor and the measurement system
      was capable of in-depth temperature sensing over 800  degrees C with a YSZ top
      layer up to 300 um. The topcoat thickness was found to have a strong effect on
      the luminescent signal level. Therefore; the measurement accuracy at high
      temperatures was reduced for samples with thick topcoats due to strong light
      attenuation. However; it seemed that the light transmissivity of YSZ topcoat
      increased with temperature; which would improve the sensor's performance at high
      temperatures. The current sensor and the measurement technology have shown great
      potential in on-line monitoring of TBC interface temperature.

PMID- 27690038
TI  - A Real-Time Web of Things Framework with Customizable Openness Considering Legacy
      Devices.
AB  - With the development of the Internet of Things (IoT), resources and applications
      based on it have emerged on a large scale. However, most efforts are "silo"
      solutions where devices and applications are tightly coupled. Infrastructures are
      needed to connect sensors to the Internet, open up and break the current
      application silos and move to a horizontal application mode. Based on the concept
      of Web of Things (WoT), many infrastructures have been proposed to integrate the
      physical world with the Web. However, issues such as no real-time guarantee, lack
      of fine-grained control of data, and the absence of explicit solutions for
      integrating heterogeneous legacy devices, hinder their widespread and practical
      use. To address these issues, this paper proposes a WoT resource framework that
      provides the infrastructures for the customizable openness and sharing of users'
      data and resources under the premise of ensuring the real-time behavior of their
      own applications. The proposed framework is validated by actual systems and
      experimental evaluations.

PMID- 27690039
TI  - An Impedance-Based Mold Sensor with on-Chip Optical Reference.
AB  - A new miniaturized sensor system with an internal optical reference for the
      detection of mold growth is presented. The sensor chip comprises a reaction
      chamber provided with a culture medium that promotes the growth of mold species
      from mold spores. The mold detection is performed by measuring impedance changes
      with integrated electrodes fabricated inside the reaction chamber. The impedance
      change in the culture medium is caused by shifts in the pH (i.e., from 5.5 to 8)
      as the mold grows. In order to determine the absolute pH value without the need
      for calibration, a methyl red indicator dye has been added to the culture medium.
      It changes the color of the medium as the pH passes specific values. This
      colorimetric principle now acts as a reference measurement. It also allows the
      sensitivity of the impedance sensor to be established in terms of impedance
      change per pH unit. Major mold species that are involved in the contamination of
      food, paper and indoor environments, like Fusarium oxysporum, Fusarium
      incarnatum, Eurotium amstelodami, Aspergillus penicillioides and Aspergillus
      restrictus, have been successfully analyzed on-chip.

PMID- 27690040
TI  - Design of a Sub-Picosecond Jitter with Adjustable-Range CMOS Delay-Locked Loop
      for High-Speed and Low-Power Applications.
AB  - A Delay-Locked Loop (DLL) with a modified charge pump circuit is proposed for
      generating high-resolution linear delay steps with sub-picosecond jitter
      performance and adjustable delay range. The small-signal model of the modified
      charge pump circuit is analyzed to bring forth the relationship between the DLL's
      internal control voltage and output time delay. Circuit post-layout simulation
      shows that a 0.97 ps delay step within a 69 ps delay range with 0.26 ps Root-Mean
      Square (RMS) jitter performance is achievable using a standard 0.13 um
      Complementary Metal-Oxide Semiconductor (CMOS) process. The post-layout
      simulation results show that the power consumption of the proposed DLL
      architecture's circuit is 0.1 mW when the DLL is operated at 2 GHz.

PMID- 27690041
TI  - Colorimetric Integrated PCR Protocol for Rapid Detection of Vibrio
      parahaemolyticus.
AB  - Rapid detection of pathogens is of great significance for food safety and disease
      diagnosis. A new colorimetric method for rapid and easy detection of Vibrio
      parahaemolyticus (V. parahaemolyticus or Vp) has been developed in this research.
      A specific sequence was designed and integrated with the forward primer for
      molecular detection of Vp. This specific sequence was tested and treated as the
      horseradish peroxidase (HRP)-mimicking DNAzyme and could be amplified during the
      polymerase chain reaction (PCR) process. The products of PCR including the
      sequence of HRP-mimicking DNAzyme could produce the distinguished color in the
      presence of catalysis substrates. The optical signal of the catalysis reaction,
      which is in a linear relationship with the initial template of Vp, could be
      determined with the naked eye or measured with Ultraviolet-visible (UV-vis) for
      qualitative and quantitative detections, respectively. Based on the optical
      signal intensity, rapid and easy detection of Vp was successfully achieved with
      satisfied sensitivity and specificity. Furthermore, the detection of tdh, trh,
      tlh and toxR virulence genes of two Vp species (Vp 33847 and Vp 17802) were all
      performed successfully with this developed colorimetric integrated PCR protocol,
      which demonstrated potential applicability for the rapid detection of other
      bacteria.

PMID- 27690042
TI  - A Hybrid Secure Scheme for Wireless Sensor Networks against Timing Attacks Using
      Continuous-Time Markov Chain and Queueing Model.
AB  - Wireless sensor networks (WSNs) have recently gained popularity for a wide
      spectrum of applications. Monitoring tasks can be performed in various
      environments. This may be beneficial in many scenarios, but it certainly exhibits
      new challenges in terms of security due to increased data transmission over the
      wireless channel with potentially unknown threats. Among possible security issues
      are timing attacks, which are not prevented by traditional cryptographic
      security. Moreover, the limited energy and memory resources prohibit the use of
      complex security mechanisms in such systems. Therefore, balancing between
      security and the associated energy consumption becomes a crucial challenge. This
      paper proposes a secure scheme for WSNs while maintaining the requirement of the
      security-performance tradeoff. In order to proceed to a quantitative treatment of
      this problem, a hybrid continuous-time Markov chain (CTMC) and queueing model are
      put forward, and the tradeoff analysis of the security and performance attributes
      is carried out. By extending and transforming this model, the mean time to
      security attributes failure is evaluated. Through tradeoff analysis, we show that
      our scheme can enhance the security of WSNs, and the optimal rekeying rate of the
      performance and security tradeoff can be obtained.

PMID- 27690043
TI  - Fast Industrial Inspection of Optical Thin Film Using Optical Coherence
      Tomography.
AB  - An application of spectral domain optical coherence tomography (SD-OCT) was
      demonstrated for a fast industrial inspection of an optical thin film panel. An
      optical thin film sample similar to a liquid crystal display (LCD) panel was
      examined. Two identical SD-OCT systems were utilized for parallel scanning of a
      complete sample in half time. Dual OCT inspection heads were utilized for
      transverse (fast) scanning, while a stable linear motorized translational stage
      was used for lateral (slow) scanning. The cross-sectional and volumetric images
      of an optical thin film sample were acquired to detect the defects in glass and
      other layers that are difficult to observe using visual inspection methods. The
      rapid inspection enabled by this setup led to the early detection of product
      defects on the manufacturing line, resulting in a significant improvement in the
      quality assurance of industrial products.

PMID- 27690045
TI  - Towards Enhanced Gas Sensor Performance with Fluoropolymer Membranes.
AB  - In this paper we report on how to increase the selectivity of gas sensors by
      using fluoropolymer membranes. The mass transport of polar and non-polar gases
      through a polymer membrane matrix was studied by systematic selection of polymers
      with different degrees of fluorination, as well as polymers whose monomers have
      ether groups (-O-) in addition to fluorine groups (-F). For the study, a set of
      application-relevant gases including H2, CO, CO2, NO2, methane, ethanol, acetone,
      and acetaldehyde as well as various concentrations of relative humidity were
      used. These gases have different functional groups and polarities, yet have a
      similar kinetic diameter and are therefore typically difficult to separate. The
      concentrations of the gases were chosen according to international indicative
      limit values (TWA, STEL). To measure the concentration in the feed and permeate,
      we used tin-dioxide-based metal oxide gas sensors with palladium catalyst
      (SnO2:Pd), catalytic sensors (also SnO2:Pd-based) and thermal conductivity
      sensors. This allows a close examination of the interdependence of diffusion and
      physicochemical operating principle of the sensor. Our goal is to increase the
      selectivity of gas sensors by using inexpensive fluoropolymer membranes. The
      measurements showed that through membranes with low polarity, preferably non
      polar gases are transported. Furthermore, the degree of crystallization
      influences the permeability and selectivity of a polymer membrane. Basically the
      polar polymers showed a higher permeability to water vapor and polar substances
      than non-polar polymer membranes.

PMID- 27690044
TI  - A Toolbox of Genetically Encoded FRET-Based Biosensors for Rapid l-Lysine
      Analysis.
AB  - Background: The fast development of microbial production strains for basic and
      fine chemicals is increasingly carried out in small scale cultivation systems to
      allow for higher throughput. Such parallelized systems create a need for new
      rapid online detection systems to quantify the respective target compound. In
      this regard, biosensors, especially genetically encoded Forster resonance energy
      transfer (FRET)-based biosensors, offer tremendous opportunities. As a proof-of
      concept, we have created a toolbox of FRET-based biosensors for the ratiometric
      determination of l-lysine in fermentation broth. Methods: The sensor toolbox was
      constructed based on a sensor that consists of an optimized central lysine
      /arginine-/ornithine-binding protein (LAO-BP) flanked by two fluorescent proteins
      (enhanced cyan fluorescent protein (ECFP), Citrine). Further sensor variants with
      altered affinity and sensitivity were obtained by circular permutation of the
      binding protein as well as the introduction of flexible and rigid linkers between
      the fluorescent proteins and the LAO-BP, respectively. Results: The sensor
      prototype was applied to monitor the extracellular l-lysine concentration of the
      l-lysine producing Corynebacterium glutamicum (C. glutamicum) strain DM1933 in a
      BioLector(r) microscale cultivation device. The results matched well with data
      obtained by HPLC analysis and the Ninhydrin assay, demonstrating the high
      potential of FRET-based biosensors for high-throughput microbial bioprocess
      optimization.

PMID- 27690046
TI  - Atmospheric Measurements by Ultra-Light SpEctrometer (AMULSE) Dedicated to
      Vertical Profile in Situ Measurements of Carbon Dioxide (CO2) Under Weather
      Balloons: Instrumental Development and Field Application.
AB  - The concentration of greenhouse gases in the atmosphere plays an important role
      in the radiative effects in the Earth's climate system. Therefore, it is crucial
      to increase the number of atmospheric observations in order to quantify the
      natural sinks and emission sources. We report in this paper the development of a
      new compact lightweight spectrometer (1.8 kg) called AMULSE based on near
      infrared laser technology at 2.04 um coupled to a 6-m open-path multipass cell.
      The measurements were made using the Wavelength Modulation Spectroscopy (WMS)
      technique and the spectrometer is hence dedicated to in situ measuring the
      vertical profiles of the CO2 at high precision levels (sigmaAllan = 0.96 ppm in 1
      s integration time (1sigma)) and with high temporal/spatial resolution (1 Hz/5 m)
      using meteorological balloons. The instrument is compact, robust, cost-effective,
      fully autonomous, has low-power consumption, a non-intrusive probe and is plug &
      play. It was first calibrated and validated in the laboratory and then used for
      17 successful flights up to 10 km altitude in the region Champagne-Ardenne,
      France in 2014. A rate of 100% of instrument recovery was validated due to the
      pre-localization prediction of the Meteo-France based on the flight simulation
      software.

PMID- 27690047
TI  - A Fourier Transform Spectrometer Based on an Electrothermal MEMS Mirror with
      Improved Linear Scan Range.
AB  - A Fourier transform spectrometer (FTS) that incorporates a closed-loop
      controlled, electrothermally actuated microelectromechanical systems (MEMS)
      micromirror is proposed and experimentally verified. The scan range and the
      tilting angle of the mirror plate are the two critical parameters for MEMS-based
      FTS. In this work, the MEMS mirror with a footprint of 4.3 mm * 3.1 mm is based
      on a modified lateral-shift-free (LSF) bimorph actuator design with large piston
      and reduced tilting. Combined with a position-sensitive device (PSD) for tilt
      angle sensing, the feedback controlled MEMS mirror generates a 430 um stable
      linear piston scan with the mirror plate tilting angle less than +/-0.002 degrees
      . The usable piston scan range is increased to 78% of the MEMS mirror's full scan
      capability, and a spectral resolution of 0.55 nm at 531.9 nm wavelength, has been
      achieved. It is a significant improvement compared to the prior work.

PMID- 27690048
TI  - Planar Indium Tin Oxide Heater for Improved Thermal Distribution for Metal Oxide
      Micromachined Gas Sensors.
AB  - Metal oxide gas sensors with integrated micro-hotplate structures are widely used
      in the industry and they are still being investigated and developed. Metal oxide
      gas sensors have the advantage of being sensitive to a wide range of organic and
      inorganic volatile compounds, although they lack selectivity. To introduce
      selectivity, the operating temperature of a single sensor is swept, and the
      measurements are fed to a discriminating algorithm. The efficiency of those data
      processing methods strongly depends on temperature uniformity across the active
      area of the sensor. To achieve this, hot plate structures with complex resistor
      geometries have been designed and additional heat-spreading structures have been
      introduced. In this work we designed and fabricated a metal oxide gas sensor
      integrated with a simple square planar indium tin oxide (ITO) heating element, by
      using conventional micromachining and thin-film deposition techniques. Power
      consumption-dependent surface temperature measurements were performed. A 420 
      degrees C working temperature was achieved at 120 mW power consumption.
      Temperature distribution uniformity was measured and a 17  degrees C difference
      between the hottest and the coldest points of the sensor at an operating
      temperature of 290  degrees C was achieved. Transient heat-up and cool-down cycle
      durations are measured as 40 ms and 20 ms, respectively.

PMID- 27690049
TI  - Development of a Flexible Non-Metal Electrode for Cell Stimulation and Recording.
AB  - This study presents a method of producing flexible electrodes for potentially
      simultaneously stimulating and measuring cellular signals in retinal cells.
      Currently, most multi-electrode applications rely primarily on etching, but the
      metals involved have a certain degree of brittleness, leaving them prone to
      cracking under prolonged pressure. This study proposes using silver chloride ink
      as a conductive metal, and polydimethysiloxane (PDMS) as the substrate to provide
      electrodes with an increased degree of flexibility to allow them to bend. This
      structure is divided into the electrode layer made of PDMS and silver chloride
      ink, and a PDMS film coating layer. PDMS can be mixed in different proportions to
      modify the degree of rigidity. The proposed method involved three steps. The
      first segment entailed the manufacturing of the electrode, using silver chloride
      ink as the conductive material, and using computer software to define the
      electrode size and micro-engraving mechanisms to produce the electrode pattern.
      The resulting uniform PDMS pattern was then baked onto the model, and the flow
      channel was filled with the conductive material before air drying to produce the
      required electrode. In the second stage, we tested the electrode, using an
      impedance analyzer to measure electrode cyclic voltammetry and impedance. In the
      third phase, mechanical and biocompatibility tests were conducted to determine
      electrode properties. This study aims to produce a flexible, non-metallic sensing
      electrode which fits snugly for use in a range of measurement applications.

PMID- 27690050
TI  - Ontology-Based High-Level Context Inference for Human Behavior Identification.
AB  - Recent years have witnessed a huge progress in the automatic identification of
      individual primitives of human behavior, such as activities or locations.
      However, the complex nature of human behavior demands more abstract contextual
      information for its analysis. This work presents an ontology-based method that
      combines low-level primitives of behavior, namely activity, locations and
      emotions, unprecedented to date, to intelligently derive more meaningful high
      level context information. The paper contributes with a new open ontology
      describing both low-level and high-level context information, as well as their
      relationships. Furthermore, a framework building on the developed ontology and
      reasoning models is presented and evaluated. The proposed method proves to be
      robust while identifying high-level contexts even in the event of erroneously
      detected low-level contexts. Despite reasonable inference times being obtained
      for a relevant set of users and instances, additional work is required to scale
      to long-term scenarios with a large number of users.

PMID- 27690051
TI  - Analysis on Target Detection and Classification in LTE Based Passive Forward
      Scattering Radar.
AB  - The passive bistatic radar (PBR) system can utilize the illuminator of
      opportunity to enhance radar capability. By utilizing the forward scattering
      technique and procedure into the specific mode of PBR can provide an improvement
      in target detection and classification. The system is known as passive Forward
      Scattering Radar (FSR). The passive FSR system can exploit the peculiar advantage
      of the enhancement in forward scatter radar cross section (FSRCS) for target
      detection. Thus, the aim of this paper is to show the feasibility of passive FSR
      for moving target detection and classification by experimental analysis and
      results. The signal source is coming from the latest technology of 4G Long-Term
      Evolution (LTE) base station. A detailed explanation on the passive FSR receiver
      circuit, the detection scheme and the classification algorithm are given. In
      addition, the proposed passive FSR circuit employs the self-mixing technique at
      the receiver; hence the synchronization signal from the transmitter is not
      required. The experimental results confirm the passive FSR system's capability
      for ground target detection and classification. Furthermore, this paper
      illustrates the first classification result in the passive FSR system. The great
      potential in the passive FSR system provides a new research area in passive radar
      that can be used for diverse remote monitoring applications.

PMID- 27690052
TI  - Integration of Error Compensation of Coordinate Measuring Machines into Feature
      Measurement: Part I-Model Development.
AB  - The development of an error compensation model for coordinate measuring machines
      (CMMs) and its integration into feature measurement is presented. CMMs are
      widespread and dependable instruments in industry and laboratories for
      dimensional measurement. From the tip probe sensor to the machine display, there
      is a complex transformation of probed point coordinates through the geometrical
      feature model that makes the assessment of accuracy and uncertainty measurement
      results difficult. Therefore, error compensation is not standardized, conversely
      to other simpler instruments. Detailed coordinate error compensation models are
      generally based on CMM as a rigid-body and it requires a detailed mapping of the
      CMM's behavior. In this paper a new model type of error compensation is proposed.
      It evaluates the error from the vectorial composition of length error by axis and
      its integration into the geometrical measurement model. The non-explained
      variability by the model is incorporated into the uncertainty budget. Model
      parameters are analyzed and linked to the geometrical errors and uncertainty of
      CMM response. Next, the outstanding measurement models of flatness, angle, and
      roundness are developed. The proposed models are useful for measurement
      improvement with easy integration into CMM signal processing, in particular in
      industrial environments where built-in solutions are sought. A battery of
      implementation tests are presented in Part II, where the experimental endorsement
      of the model is included.

PMID- 27690053
TI  - Spectral Skyline Separation: Extended Landmark Databases and Panoramic Imaging.
AB  - Evidence from behavioral experiments suggests that insects use the skyline as a
      cue for visual navigation. However, changes of lighting conditions, over hours,
      days or possibly seasons, significantly affect the appearance of the sky and
      ground objects. One possible solution to this problem is to extract the "skyline"
      by an illumination-invariant classification of the environment into two classes,
      ground objects and sky. In a previous study (Insect models of illumination
      invariant skyline extraction from UV (ultraviolet) and green channels), we
      examined the idea of using two different color channels available for many
      insects (UV and green) to perform this segmentation. We found out that for
      suburban scenes in temperate zones, where the skyline is dominated by trees and
      artificial objects like houses, a "local" UV segmentation with adaptive
      thresholds applied to individual images leads to the most reliable
      classification. Furthermore, a "global" segmentation with fixed thresholds
      (trained on an image dataset recorded over several days) using UV-only
      information is only slightly worse compared to using both the UV and green
      channel. In this study, we address three issues: First, to enhance the limited
      range of environments covered by the dataset collected in the previous study, we
      gathered additional data samples of skylines consisting of minerals (stones,
      sand, earth) as ground objects. We could show that also for mineral-rich
      environments, UV-only segmentation achieves a quality comparable to multi
      spectral (UV and green) segmentation. Second, we collected a wide variety of
      ground objects to examine their spectral characteristics under different lighting
      conditions. On the one hand, we found that the special case of diffusely
      illuminated minerals increases the difficulty to reliably separate ground objects
      from the sky. On the other hand, the spectral characteristics of this collection
      of ground objects covers well with the data collected in the skyline databases,
      increasing, due to the increased variety of ground objects, the validity of our
      findings for novel environments. Third, we collected omnidirectional images, as
      often used for visual navigation tasks, of skylines using an UV-reflective
      hyperbolic mirror. We could show that "local" separation techniques can be
      adapted to the use of panoramic images by splitting the image into segments and
      finding individual thresholds for each segment. Contrarily, this is not possible
      for 'global' separation techniques.

PMID- 27690054
TI  - Ensemble of One-Class Classifiers for Personal Risk Detection Based on Wearable
      Sensor Data.
AB  - This study introduces the One-Class K-means with Randomly-projected features
      Algorithm (OCKRA). OCKRA is an ensemble of one-class classifiers built over
      multiple projections of a dataset according to random feature subsets. Algorithms
      found in the literature spread over a wide range of applications where ensembles
      of one-class classifiers have been satisfactorily applied; however, none is
      oriented to the area under our study: personal risk detection. OCKRA has been
      designed with the aim of improving the detection performance in the problem posed
      by the Personal RIsk DEtection(PRIDE) dataset. PRIDE was built based on 23 test
      subjects, where the data for each user were captured using a set of sensors
      embedded in a wearable band. The performance of OCKRA was compared against
      support vector machine and three versions of the Parzen window classifier. On
      average, experimental results show that OCKRA outperformed the other classifiers
      for at least 0.53% of the area under the curve (AUC). In addition, OCKRA achieved
      an AUC above 90% for more than 57% of the users.

PMID- 27690056
TI  - Monitoring Heritage Buildings with Open Source Hardware Sensors: A Case Study of
      the Mosque-Cathedral of Cordoba.
AB  - A number of physical factors can adversely affect cultural heritage. Therefore,
      monitoring parameters involved in the deterioration process, principally
      temperature and relative humidity, is useful for preventive conservation. In this
      study, a total of 15 microclimate stations using open source hardware were
      developed and stationed at the Mosque-Cathedral of Cordoba, which is registered
      with UNESCO for its outstanding universal value, to assess the behavior of
      interior temperature and relative humidity in relation to exterior weather
      conditions, public hours and interior design. Long-term monitoring of these
      parameters is of interest in terms of preservation and reducing the costs of
      future conservation strategies. Results from monitoring are presented to
      demonstrate the usefulness of this system.

PMID- 27690055
TI  - Arbitrarily Accessible 3D Microfluidic Device for Combinatorial High-Throughput
      Drug Screening.
AB  - Microfluidics-based drug-screening systems have enabled efficient and high
      throughput drug screening, but their routine uses in ordinary labs are limited
      due to the complexity involved in device fabrication and system setup. In this
      work, we report an easy-to-use and low-cost arbitrarily accessible 3D
      microfluidic device that can be easily adopted by various labs to perform
      combinatorial assays for high-throughput drug screening. The device is capable of
      precisely performing automatic and simultaneous reagent loading and aliquoting
      tasks and performing multistep assays with arbitrary sequences. The device is not
      intended to compete with other microfluidic technologies regarding ultra-low
      reaction volume. Instead, its freedom from tubing or pumping systems and easy
      operation makes it an ideal platform for routine high-throughput drug screening
      outside traditional microfluidic labs. The functionality and quantitative
      reliability of the 3D microfluidic device were demonstrated with a histone
      acetyltransferase-based drug-screening assay using the recombinant Plasmodium
      falciparum GCN5 enzyme, benchmarked with a traditional microtiter plate-based
      method. This arbitrarily accessible, multistep capable, low-cost, and easy-to-use
      device can be widely adopted in various combinatorial assays beyond high
      throughput drug screening.

PMID- 27690057
TI  - A Mechatronic Loading Device to Stimulate Bone Growth via a Human Knee.
AB  - This paper presents the design of an innovative device that applies dynamic
      mechanical load to human knee joints. Dynamic loading is employed by applying
      cyclic and periodic force on a target area. The repeated force loading was
      considered to be an effective modality for repair and rehabilitation of long
      bones that are subject to ailments like fractures, osteoporosis, osteoarthritis,
      etc. The proposed device design builds on the knowledge gained in previous animal
      and mechanical studies. It employs a modified slider-crank linkage mechanism
      actuated by a brushless Direct Current (DC) motor and provides uniform and cyclic
      force. The functionality of the device was simulated in a software environment
      and the structural integrity was analyzed using a finite element method for the
      prototype construction. The device is controlled by a microcontroller that is
      programmed to provide the desired loading force at a predetermined frequency and
      for a specific duration. The device was successfully tested in various
      experiments for its usability and full functionality. The results reveal that the
      device works according to the requirements of force magnitude and operational
      frequency. This device is considered ready to be used for a clinical study to
      examine whether controlled knee-loading could be an effective regimen for
      treating the stated bone-related ailments.

PMID- 27690058
TI  - Vehicle Maneuver Detection with Accelerometer-Based Classification.
AB  - In the mobile computing era, smartphones have become instrumental tools to
      develop innovative mobile context-aware systems. In that sense, their usage in
      the vehicular domain eases the development of novel and personal transportation
      solutions. In this frame, the present work introduces an innovative mechanism to
      perceive the current kinematic state of a vehicle on the basis of the
      accelerometer data from a smartphone mounted in the vehicle. Unlike previous
      proposals, the introduced architecture targets the computational limitations of
      such devices to carry out the detection process following an incremental
      approach. For its realization, we have evaluated different classification
      algorithms to act as agents within the architecture. Finally, our approach has
      been tested with a real-world dataset collected by means of the ad hoc mobile
      application developed.

PMID- 27690060
TI  - Nanosized Drug Delivery Systems in Gastrointestinal Targeting: Interactions with
      Microbiota.
AB  - The new age of nanotechnology has signaled a stream of entrepreneurial
      possibilities in various areas, form industry to medicine. Drug delivery has
      benefited the most by introducing nanostructured systems in the transport and
      controlled release of therapeutic molecules at targeted sites associated with a
      particular disease. As many nanosized particles reach the gastrointestinal tract
      by various means, their interactions with the molecular components of this highly
      active niche are intensively investigated. The well-characterized antimicrobial
      activities of numerous nanoparticles are currently being considered as a reliable
      and efficient alternative to the eminent world crisis in antimicrobial drug
      discovery. The interactions of nanosystems present in the gastrointestinal route
      with host microbiota is unavoidable; hence, a major research initiative is needed
      to explore the mechanisms and effects of these nanomaterials on microbiota and
      the impact that microbiota may have in the outcome of therapies entailing drug
      delivery nanosystems through the gastrointestinal route. These coordinated
      studies will provide novel techniques to replace or act synergistically with
      current technologies and help develop new treatments for major diseases via the
      discovery of unique antimicrobial molecules.

PMID- 27690061
TI  - Bioactive Chaetoglobosins from the Mangrove Endophytic Fungus Penicillium
      chrysogenum.
AB  - A novel chaetoglobosin named penochalasin I (1) with a unprecedented six-cyclic
      6/5/6/5/6/13 fused ring system, and another new chaetoglobosin named penochalasin
      J (2), along with chaetoglobosins G, F, C, A, E, armochaetoglobosin I, and
      cytoglobosin C (3-9) were isolated from the culture of Penicillium chrysogenum
      V11. Their structures were elucidated by 1D, 2D NMR spectroscopic analysis and
      high resolution mass spectroscopic data. The absolute configuration of compounds
      1 and 2 were determined by comparing the theoretical electronic circular
      dichroism (ECD) calculation with the experimental CD. Compound 1 was the first
      example, with a six-cyclic fused ring system formed by the connection of C-5 and
      C-2' of the chaetoglobosin class. Compounds 5-8 remarkably inhibited the plant
      pathogenic fungus R. solani (minimum inhibitory concentrations (MICs) = 11.79
      23.66 MUM), and compounds 2, 6, and 7 greatly inhibited C. gloeosporioides (MICs
      = 23.58-47.35 MUM), showing an antifungal activity higher than that of
      carbendazim. Compound 1 exhibited marked cytotoxicity against MDA-MB-435 and SGC
      7901 cells (IC50 < 10 MUM), and compounds 6 and 9 showed potent cytotoxicity
      against SGC-7901 and A549 cells (IC50 < 10 MUM).

PMID- 27690059
TI  - Lactoferrin from Milk: Nutraceutical and Pharmacological Properties.
AB  - Lactoferrin is an iron-binding protein present in large quantities in colostrum
      and in breast milk, in external secretions and in polymorphonuclear leukocytes.
      Lactoferrin's main function is non-immune protection. Among several protective
      activities shown by lactoferrin, those displayed by orally administered
      lactoferrin are: (i) antimicrobial activity, which has been presumed due to iron
      deprivation, but more recently attributed also to a specific interaction with the
      bacterial cell wall and extended to viruses and parasites; (ii) immunomodulatory
      activity, with a direct effect on the development of the immune system in the
      newborn, together with a specific antinflammatory effects; (iii) a more recently
      discovered anticancer activity. It is worth noting that most of the protective
      activities of lactoferrin have been found, sometimes to a greater extent, also in
      peptides derived from limited proteolysis of lactoferrin that could be generated
      after lactoferrin ingestion. Lactoferrin could therefore be considered an ideal
      nutraceutic product because of its relatively cheap production from bovine milk
      and of its widely recognized tolerance after ingestion, along with its well
      demonstrated protective activities. The most important protective activities
      shown by orally administered bovine lactoferrin are reviewed in this article.

PMID- 27690063
TI  - Empirical Likelihood-Based ANOVA for Trimmed Means.
AB  - In this paper, we introduce an alternative to Yuen's test for the comparison of
      several population trimmed means. This nonparametric ANOVA type test is based on
      the empirical likelihood (EL) approach and extends the results for one population
      trimmed mean from Qin and Tsao (2002). The results of our simulation study
      indicate that for skewed distributions, with and without variance heterogeneity,
      Yuen's test performs better than the new EL ANOVA test for trimmed means with
      respect to control over the probability of a type I error. This finding is in
      contrast with our simulation results for the comparison of means, where the EL
      ANOVA test for means performs better than Welch's heteroscedastic F test. The
      analysis of a real data example illustrates the use of Yuen's test and the new EL
      ANOVA test for trimmed means for different trimming levels. Based on the results
      of our study, we recommend the use of Yuen's test for situations involving the
      comparison of population trimmed means between groups of interest.

PMID- 27690062
TI  - Novel Spray Dried Glycerol 2-Phosphate Cross-Linked Chitosan Microparticulate
      Vaginal Delivery System-Development, Characterization and Cytotoxicity Studies.
AB  - Chitosan microparticulate delivery systems containing clotrimazole were prepared
      by a spray drying technique using glycerol 2-phosphate as an ion cross-linker.
      The impact of a cross-linking ratio on microparticle characteristics was
      evaluated. Drug-free and drug-loaded unmodified or ion cross-linked chitosan
      microparticles were examined for the in vitro cytotoxicity in VK2/E6E7 human
      vaginal epithelial cells. The presence of glycerol 2-phosphate influenced drug
      loading and encapsulation efficacy in chitosan microparticles. By increasing the
      cross-linking ratio, the microparticles with lower diameter, moisture content and
      smoother surface were observed. Mucoadhesive studies displayed that all
      formulations possessed mucoadhesive properties. The in vitro release profile of
      clotrimazole was found to alter considerably by changing the glycerol 2
      phosphate/chitosan ratio. Results from cytotoxicity studies showed occurrence of
      apoptotic cells in the presence of chitosan and ion cross-linked chitosan
      microparticles, followed by a loss of membrane potential suggesting that cell
      death might go through the mitochondrial apoptotic pathway.

PMID- 27690064
TI  - The Built Environment-A Missing "Cause of the Causes" of Non-Communicable
      Diseases.
AB  - The United Nations "25 * 25 Strategy" of decreasing non-communicable diseases
      (NCDs), including cardiovascular diseases, diabetes, cancer and chronic
      respiratory diseases, by 25% by 2025 does not appear to take into account all
      causes of NCDs. Its focus is on a few diseases, which are often linked with life
      style factors with "voluntary" "modifiable behavioral risk factors" causes
      tending towards an over-simplification of the issues. We propose to add some
      aspects of our built environment related to hazardous building materials, and
      detailed form of the construction of infrastructure and buildings, which we think
      are some of the missing causes of NCDs. Some of these could be termed
      "involuntary causes", as they relate to factors that are beyond the control of
      the general public.

PMID- 27690065
TI  - A Case Study of Environmental Injustice: The Failure in Flint.
AB  - The failure by the city of Flint, Michigan to properly treat its municipal water
      system after a change in the source of water, has resulted in elevated lead
      levels in the city's water and an increase in city children's blood lead levels.
      Lead exposure in young children can lead to decrements in intelligence,
      development, behavior, attention and other neurological functions. This lack of
      ability to provide safe drinking water represents a failure to protect the
      public's health at various governmental levels. This article describes how the
      tragedy happened, how low-income and minority populations are at particularly
      high risk for lead exposure and environmental injustice, and ways that we can
      move forward to prevent childhood lead exposure and lead poisoning, as well as
      prevent future Flint-like exposure events from occurring. Control of the
      manufacture and use of toxic chemicals to prevent adverse exposure to these
      substances is also discussed. Environmental injustice occurred throughout the
      Flint water contamination incident and there are lessons we can all learn from
      this debacle to move forward in promoting environmental justice.

PMID- 27690066
TI  - Relationship between Pesticide Metabolites, Cytokine Patterns, and Asthma-Related
      Outcomes in Rural Women Workers.
AB  - The objective of this study was to investigate the relationship between exposure
      to organophosphate (OP) and pyrethroid (PYR) pesticides with serum cytokine
      patterns and asthma-related outcomes among rural women workers. A cross-sectional
      study was conducted among rural women (n = 211), including those working and
      living on farms and nearby town dwellers. Pesticide exposure was assessed using
      urinary metabolite concentrations of OP and PYR pesticides. Health outcome
      assessment was ascertained through the European Community Respiratory Health
      Survey (ECRHS) questionnaire, fractional exhaled nitric oxide (FeNO), and serum
      cytokines associated with asthma. The prevalence of doctor-diagnosed asthma was
      11%, adult-onset asthma 9%, and current asthma 6%. In this population, the
      proportion of T helper type 2 (Th2) cytokines (interleukin (IL)-4, IL-5, and IL
      13) detectable in subjects was between 18% and 40%, while the proportion of non
      Th2 cytokines (IL-6, IL-8, IL-10, IL-17, and interferon gamma) was between 35%
      and 71%. Most Th2 and non-Th2 cytokines were positively associated with either OP
      or PYR metabolites. Non-Th2 cytokines showed much stronger associations with OP
      metabolites (Dimethyl phosphate OR = 4.23; 95% CI: 1.54-11.65) than Th2 cytokines
      (Dimethyl phosphate OR = 1.69; 95% CI: 0.83-3.46). This study suggests that
      exposure to most OP and some PYR pesticides may be associated with asthma-related
      cytokines, with non-Th2 cytokines demonstrating consistently stronger
      relationships.

PMID- 27690067
TI  - Patterns of Psychiatric Outpatient Practice in Taiwan: A Nationwide Survey.
AB  - (1) Background: Limited studies have utilized nationwide data to assess the
      patterns of psychiatric practice in other countries. In this study, data from the
      National Health Insurance Research Database in Taiwan (NHIRD-TW) for 2012 was
      analyzed to determine the patterns of psychiatric outpatient practice in Taiwan;
      (2) Methods: To determine the patterns of psychiatric outpatient practice in
      Taiwan, the data were drawn from the datasets of Taiwan's National Health
      Insurance Research Database for 2012, with 619,760 records of outpatient visits
      representing 1/500 of all the claims in Taiwan for that year. The analysis of
      psychiatric outpatient visits included patient demographics, diagnoses, and
      prescribed medications; (3) Results: Neurotic disorders were the most prevalent
      diagnoses (43.1%, n = 5714). Hypnotics-sedatives and anxiolytics were prescribed
      in 51.7% (n = 6850) and 39.1% (n = 5181) of psychiatric visits, respectively,
      with zolpidem being the most commonly prescribed drug (22.6%, n = 2998); and (4)
      Conclusion: Hypnotics and sedatives were widely prescribed for the outpatient
      population, and zolpidem had the highest annual prevalence of use. These findings
      deserve the attention of clinicians and policy makers for monitoring the abuse
      and dependence of these agents and subsequent adverse events.

PMID- 27690068
TI  - A Brief Cognitive-Behavioral Psycho-Education (B-CBE) Program for Managing Stress
      and Anxiety of Main Family Caregivers of Patients in the Intensive Care Unit.
AB  - Having a loved one in the intensive care unit (ICU) is a stressful event, which
      may cause a high level of anxiety to the family members. This could threaten
      their wellbeing and ability to support the patients in, or after discharge from,
      the ICU. To investigate the outcomes of a brief cognitive-behavioral psycho
      education program (B-CBE) to manage stress and anxiety of the main family
      caregivers (MFCs), a pragmatic quasi-experimental study involving 45 participants
      (treatment group: 24; control group: 21) was conducted in an ICU. The Depression
      and Anxiety Stress Scale and the Critical Care Family Need Inventory were used to
      evaluate the primary outcomes on stress and anxiety, and satisfaction with family
      needs. The treatment group reported significantly better improvement in the
      information satisfaction score compared to the control group (p < 0.05; eta2 =
      0.09). Overall main effects were observed on the stress (p < 0.01; eta2 = 0.20),
      anxiety (p < 0.01; eta2 = 0.18), depression (p < 0.05; eta2 = 0.13), support
      satisfaction (p < 0.05; eta2 = 0.13), and comfort satisfaction (p < 0.05; eta2 =
      0.11) scores. The experience of this study suggest that MFCs are in great need of
      additional support like B-CBE to manage their stress and anxiety. Given the
      brevity of B-CBE, it is practical for critical care nurses to deliver and MFCs to
      take within the industrious context of an ICU. More studies are needed to
      investigate these types of brief psychological interventions.

PMID- 27690069
TI  - Is Multidirectional UV Exposure Responsible for Increasing Melanoma Prevalence
      with Altitude? A Hypothesis Based on Calculations with a 3D-Human Exposure Model.
AB  - In a recent study, melanoma incidence rates for Austrian inhabitants living at
      higher altitudes were found to increase by as much as 30% per 100 m altitude.
      This strong increase cannot simply be explained by the known increase of
      erythemally-weighted irradiance with altitude, which ranges between 0.5% and 4%
      per 100 m. We assume that the discrepancy is partially explainable by upwelling
      UV radiation; e.g., reflected by snow-covered surfaces. Therefore, we present an
      approach where the human UV exposure is derived by integrating incident radiation
      over the 3D geometry of a human body, which enables us to take upwelling
      radiation into account. Calculating upwelling and downwelling radiance with a
      radiative transfer model for a snow-free valley and for snow-covered mountain
      terrain (with albedo of 0.6) yields an increase in UV exposure by 10% per 100 m
      altitude. The results imply that upwelling radiation plays a significant role in
      the increase of melanoma incidence with altitude.

PMID- 27690070
TI  - Has Child Restraint System Use Increased among Parents of Children in Shantou,
      China?
AB  - OBJECTIVE: to examine parents' use of child restraint systems (CRS), and
      determine if parents' knowledge of, attitude toward, and use behavior of child
      restraint systems have improved following enactment of child restraint use laws
      in other cities. DESIGN: Observations and a cross-sectional survey of drivers
      transporting children 17 years and under were conducted at the gate of the
      schools and parking lots of hospitals in Shantou. Observers recorded the seating
      location of child passengers, the type of restraint, and appropriate use of CRS
      and safety belts based on the observation. Knowledge of and attitudes towards use
      of CRS were reported by the driver following observation. RESULTS: Approximately
      6.6% of passengers aged 0-12 were in CRS; rate of forward-facing CRS in children
      aged 3-5 (9.9%) was higher than rear-facing CRS for children aged 0-2 (1.1%) and
      booster seat use among children aged 6-12 (0.1%). Children younger than four
      years old (OR = 3.395, 95% CI = 2.125-5.424), drivers having a college or higher
      lever education (OR = 2.908, 95% CI = 1.878-4.500) and drivers wearing seatbelt
      (OR = 3.194, 95% CI = 1.605-6.356) had greater odds of CRS use. Over half (56.6%)
      of parents might or would use CRS if they could rent CRSs with fees. CONCLUSIONS:
      The rate of CRS is still low in Shantou. Comprehensive public education programs
      supported by legislation might be an effective way to improve child passenger
      safety. Renting CRSs to parents could be a new approach to encourage use.

PMID- 27690071
TI  - Activity Pattern of Urban Adult Students in an Eastern Mediterranean Society.
AB  - Knowledge of human activity patterns is needed in air pollution exposure and
      health risk assessment. However, human activity patterns have never been
      evaluated in the Eastern Mediterranean societies. Therefore, we investigated the
      activity pattern of 285 subjects (17-63 years) in Amman, Jordan during October to
      November, 2015. The subjects spent >80% of their time indoors during weekend days
      and >85% on workdays. They spent ~4.8% and ~5.7% in transportation during weekend
      days and workdays, respectively. Males had a different activity pattern than
      females on weekend days, but both genders had similar activity patterns on
      workdays. On workdays, males spent less time indoors than females. The activity
      pattern found in this study is a bit different than that for North Americans and
      Europeans, who spend more time indoors and in transit. The activity pattern found
      in this study was very different than that observed for Koreans, who spent about
      59% and 67% indoors on workdays and weekend, respectively. The main outcomes of
      this survey can be utilized in human exposure studies. This study and the
      upcoming future studies have been encouraged and supported by the regional WHO
      office in Amman.

PMID- 27690072
TI  - A Cross-Sectional Study of Tobacco Advertising, Promotion, and Sponsorship in
      Airports across Europe and the United States.
AB  - Tobacco advertising, promotion, and sponsorship (TAPS) bans are effective and are
      increasingly being implemented in a number of venues and countries, yet the state
      of TAPS in airports and their effect on airport smoking behavior is unknown. The
      objective of this study was to evaluate the presence of TAPS in airports across
      Europe and the US, and to begin to examine the relationship between TAPS and
      smoking behaviors in airports. We used a cross-sectional study design to observe
      21 airports in Europe (11) and the US (10). Data collectors observed points of
      sale for tobacco products, types of products sold, advertisements and promotions,
      and branding or logos that appeared in the airport. Tobacco products were sold in
      95% of all airports, with significantly more sales in Europe than the US.
      Advertisements appeared mostly in post-security areas; however, airports with
      advertisements in pre-security areas had significantly more smokers observed
      outdoors than airports without advertisements in pre-security areas. Tobacco
      branding appeared in designated smoking rooms as well as on non-tobacco products
      in duty free shops. TAPS are widespread in airports in Europe and the US and
      might be associated with outdoor smoking, though further research is needed to
      better understand any relationship between the two. This study adds to a growing
      body of research on tobacco control in air transit and related issues. As smoke
      free policies advance, they should include comprehensive TAPS bans that extend to
      airport facilities.

PMID- 27690073
TI  - Temporal Trends in Geographical Variation in Breast Cancer Mortality in China,
      1973-2005: An Analysis of Nationwide Surveys on Cause of Death.
AB  - To describe geographical variation in breast cancer mortality over time, we
      analysed breast cancer mortality data from three retrospective national surveys
      on causes of death in recent decades in China. We first calculated the age
      standardized mortality rate (ASMR) for each of the 31 provinces in mainland China
      stratified by survey period (1973-1975, 1990-1992 and 2004-2005). To test whether
      the geographical variation in breast cancer mortality changed over time, we then
      estimated the rate ratio (RR) for the aggregated data for seven regions and three
      economic zones using generalized linear models. Finally, we examined the
      correlation between mortality rate and several macro-economic measures at the
      provincial level. We found that the overall ASMR increased from 2.98 per 100,000
      in 1973-1975 to 3.08 per 100,000 in 1990-1992, and to 3.85 per 100,000 in 2004
      2005. Geographical variation in breast cancer mortality also increased
      significantly over time at the regional level (p = 0.002) but not at the economic
      zone (p = 0.089) level, with RR being generally lower for Western China
      (Northwest and Southwest) and higher in Northeast China over the three survey
      periods. These temporal and spatial trends in breast cancer mortality were found
      to be correlated with per capita gross domestic product, number of hospitals and
      health centres' beds per 10,000 population and number of practicing doctors per
      10,000 population, and average number of live births for women aged 15-64. It may
      be necessary to target public health policies in China to address the widening
      geographic variation in breast cancer mortality, and to take steps to ensure that
      the ease of access and the quality of cancer care across the country is improved
      for all residents.

PMID- 27690074
TI  - Effects of Octylphenol and Bisphenol A on the Metal Cation Transporter Channels
      of Mouse Placentas.
AB  - Octylphenol (OP) and bisphenol A (BPA) are known as endocrine-disrupting
      chemicals (EDCs). During pregnancy, the expression of steroid hormone receptors
      is controlled by maternal and fetal nutrition. To evaluate the impact of EDCs
      during pregnancy, ethinyl estradiol (EE, 0.2 mg/kg/day), OP (50 mg/kg/day), and
      BPA (50 mg/kg/day) were administered to pregnant mice. The mRNA levels of TRPV6
      (transient receptor potential cation channels in subfamily V, member 6) decreased
      significantly by EE and OP. The PMCA1 (ATPase, Ca++ transporting, plasma membrane
      1) mRNA and protein levels decreased significantly by EE, OP, and BPA. CTR1
      (solute carrier family 31, member 1) and ATP7A (ATPase, Cu++ transporting, alpha
      polypeptide) expression decreased significantly by EE, OP, and BPA. The mRNA
      levels of IREG1 (iron-regulated transporter, member 1) decreased significantly by
      EE. Hephaestin (HEPH) mRNA levels decreased significantly by EE, OP, and BPA, and
      protein levels decreased significantly by BPA. As a result of
      immunohistochemistry analysis, all cation transporter proteins were found in
      labyrinth of placenta. To confirm the cytosolic level of cations, levels of
      cation level in fetal serum were measured. EE, OP, and BPA significantly reduced
      serum calcium and copper levels, and iron levels were reduced by BPA. Taken
      together, some EDCs, such as OP and BPA, could modulate the calcium, copper, and
      iron ion-transporting channels during pregnancy. The fetus relies on the mother
      for ionic transportation, and, therefore, pregnant women should avoid exposure to
      cation-channel-disrupting chemicals.

PMID- 27690075
TI  - Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly
      Used in Sunscreen Products.
AB  - Sunscreen products are predominantly regulated as over-the-counter (OTC) drugs by
      the US FDA. The "active" ingredients function as ultraviolet filters. Once a
      sunscreen product is generally recognized as safe and effective (GRASE) via an
      OTC drug review process, new formulations using these ingredients do not require
      FDA review and approval, however, the majority of ingredients have never been
      tested to uncover any potential endocrine activity and their ability to interact
      with the estrogen receptor (ER) is unknown, despite the fact that this is a very
      extensively studied target related to endocrine activity. Consequently, we have
      developed an in silico model to prioritize single ingredient estrogen receptor
      activity for use when actual animal data are inadequate, equivocal, or absent. It
      relies on consensus modeling to qualitatively and quantitatively predict ER
      binding activity. As proof of concept, the model was applied to ingredients
      commonly used in sunscreen products worldwide and a few reference chemicals. Of
      the 32 chemicals with unknown ER binding activity that were evaluated, seven were
      predicted to be active estrogenic compounds. Five of the seven were confirmed by
      the published data. Further experimental data is needed to confirm the other two
      predictions.

PMID- 27690078
TI  - An Examination of the Ethnicity-Specific Prevalence of and Factors Associated
      with Substance Use and Misuse: Cross-Sectional Analysis of Croatian and Bosniak
      Adolescents in Bosnia and Herzegovina.
AB  - Substance use and misuse (SUM) in adolescence is a significant public health
      problem and the extent to which adolescents exhibit SUM behaviors differs across
      ethnicity. This study aimed to explore the ethnicity-specific and gender-specific
      associations among sports factors, familial factors, and personal satisfaction
      with physical appearance (i.e., covariates) and SUM in a sample of adolescents
      from Federation of Bosnia and Herzegovina. In this cross-sectional study the
      participants were 1742 adolescents (17-18 years of age) from Bosnia and
      Herzegovina who were in their last year of high school education (high school
      seniors). The sample comprised 772 Croatian (558 females) and 970 Bosniak (485
      females) adolescents. Variables were collected using a previously developed and
      validated questionnaire that included questions on SUM (alcohol drinking,
      cigarette smoking, and consumption of other drugs), sport factors, parental
      education, socioeconomic status, and satisfaction with physical appearance and
      body weight. The consumption of cigarettes remains high (37% of adolescents smoke
      cigarettes), with a higher prevalence among Croatians. Harmful drinking is also
      alarming (evidenced in 28.4% of adolescents). The consumption of illicit drugs
      remains low with 5.7% of adolescents who consume drugs, with a higher prevalence
      among Bosniaks. A higher likelihood of engaging in SUM is found among children
      who quit sports (for smoking and drinking), boys who perceive themselves to be
      good looking (for smoking), and girls who are not satisfied with their body
      weight (for smoking). Higher maternal education is systematically found to be
      associated with greater SUM in Bosniak girls. Information on the associations
      presented herein could be discretely disseminated as a part of regular school
      administrative functions. The results warrant future prospective studies that
      more precisely identify the causality among certain variables.

PMID- 27690077
TI  - Are Non-Pharmacological Interventions Effective in Reducing Drug Use and
      Criminality? A Systematic and Meta-Analytical Review with an Economic Appraisal
      of These Interventions.
AB  - Background: The numbers of incarcerated people suffering from drug dependence has
      steadily risen since the 1980s and only a small proportion of these receive
      appropriate treatment. A systematic review to evaluate the effectiveness and
      economic evidence of non-pharmacological interventions for drug using offenders
      was conducted. Methods: Cochrane Collaboration criteria were used to identify
      trials across 14 databases between 2004 and 2014. A series of meta-analyses and
      an economic appraisal were conducted. Results: 43 trials were identified showing
      to have limited effect in reducing re-arrests RR 0.97 (95% CI 0.89-1.07) and drug
      use RR 0.90 (95% CI 0.80-1.00) but were found to significantly reduce re
      incarceration RR 0.70 (95% CI 0.57-0.85). Therapeutic community programs were
      found to significantly reduce the number of re-arrests RR 0.70 (95% CI 0.56
      0.87). 10 papers contained economic information. One paper presented a cost
      benefit analysis and two reported on the cost and cost effectiveness of the
      intervention. Conclusions: We suggest that therapeutic community interventions
      have some benefit in reducing subsequent re-arrest. We recommend that economic
      evaluations should form part of standard trial protocols.

PMID- 27690079
TI  - l-Arginine Enhances Resistance against Oxidative Stress and Heat Stress in
      Caenorhabditis elegans.
AB  - The antioxidant properties of l-arginine (l-Arg) in vivo, and its effect on
      enhancing resistance to oxidative stress and heat stress in Caenorhabditis
      elegans were investigated. C. elegans, a worm model popularly used in molecular
      and developmental biology, was used in the present study. Here, we report that l
      Arg, at a concentration of 1 mM, prolonged C. elegans life by 26.98% and 37.02%
      under oxidative and heat stress, respectively. Further experiments indicated that
      the longevity-extending effects of l-Arg may be exerted by its free radical
      scavenging capacity and the upregulation of aging-associated gene expression in
      worms. This work is important in the context of numerous recent studies that
      concluded that environment stresses are associated with an increased population
      death rate.

PMID- 27690076
TI  - Bioelectromagnetics Research within an Australian Context: The Australian Centre
      for Electromagnetic Bioeffects Research (ACEBR).
AB  - Mobile phone subscriptions continue to increase across the world, with the
      electromagnetic fields (EMF) emitted by these devices, as well as by related
      technologies such as Wi-Fi and smart meters, now ubiquitous. This increase in use
      and consequent exposure to mobile communication (MC)-related EMF has led to
      concern about possible health effects that could arise from this exposure.
      Although much research has been conducted since the introduction of these
      technologies, uncertainty about the impact on health remains. The Australian
      Centre for Electromagnetic Bioeffects Research (ACEBR) is a National Health and
      Medical Research Council Centre of Research Excellence that is undertaking
      research addressing the most important aspects of the MC-EMF health debate, with
      a strong focus on mechanisms, neurodegenerative diseases, cancer, and exposure
      dosimetry. This research takes as its starting point the current scientific
      status quo, but also addresses the adequacy of the evidence for the status quo.
      Risk communication research complements the above, and aims to ensure that
      whatever is found, it is communicated effectively and appropriately. This paper
      provides a summary of this ACEBR research (both completed and ongoing), and
      discusses the rationale for conducting it in light of the prevailing science.

PMID- 27690080
TI  - Vesicular Nucleo-Cytoplasmic Transport-Herpesviruses as Pioneers in Cell Biology.
AB  - Herpesviruses use a vesicle-mediated transfer of intranuclearly assembled
      nucleocapsids through the nuclear envelope (NE) for final maturation in the
      cytoplasm. The molecular basis for this novel vesicular nucleo-cytoplasmic
      transport is beginning to be elucidated in detail. The heterodimeric viral
      nuclear egress complex (NEC), conserved within the classical herpesviruses,
      mediates vesicle formation from the inner nuclear membrane (INM) by
      polymerization into a hexagonal lattice followed by fusion of the vesicle
      membrane with the outer nuclear membrane (ONM). Mechanisms of capsid inclusion as
      well as vesicle-membrane fusion, however, are largely unclear. Interestingly, a
      similar transport mechanism through the NE has been demonstrated in nuclear
      export of large ribonucleoprotein complexes during Drosophila neuromuscular
      junction formation, indicating a widespread presence of a novel concept of
      cellular nucleo-cytoplasmic transport.

PMID- 27690081
TI  - Molecular Characterization of a Trisegmented Mycovirus from the Plant Pathogenic
      Fungus Colletotrichum gloeosporioides.
AB  - A novel double-stranded RNA (dsRNA) mycovirus, consisting of three dsRNA genome
      segments and possibly belonging to the family Chrysoviridae, was isolated from
      the filamentous phytopathogenic fungus Colletotrichum gloeosporioides and
      designated as Colletotrichum gloeosprioides chrysovirus 1 (CgCV1). The three
      dsRNAs of the CgCV1 genome with lengths of 3397, 2869, and 2630 bp (dsRNAs1-3)
      were found to contain a single open reading frame (ORF) putatively encoding the
      RNA-dependent RNA polymerase (RdRp), a capsid protein, and a protease,
      respectively, all of which exhibited some degree of sequence similarity to the
      comparable putative proteins encoded by the genus Chrysovirus. The 5'- and 3'
      untranslated regions in each dsRNA segment contained similar sequences that were
      strictly conserved at the termini. Moreover, isometric virus-like particles
      (VLPs) with a diameter of approximately 40 nm were extracted from fungal mycelia.
      Phylogenetic analysis based on the conserved dsRNA1-encoded RdRp showed that
      CgCV1 is a new virus belonging to the Chrysoviridae family. BLAST analysis
      revealed the presence of CgCV1-like sequences in the chromosomes of Medicago
      truncatula and Solanum tuberosum. Moreover, some sequences in the transcriptome
      shotgun assembly (TSA) library and expressed sequence tag database (ESTdb) of
      other eudicot and monocot plants were also found to be related to CgCV1.

PMID- 27690083
TI  - The VP1u Receptor Restricts Parvovirus B19 Uptake to Permissive Erythroid Cells.
AB  - Parvovirus B19 (B19V) is a small non-enveloped virus and known as the causative
      agent for the mild childhood disease erythema infectiosum. B19V has an
      extraordinary narrow tissue tropism, showing only productive infection in
      erythroid precursor cells in the bone marrow. We recently found that the viral
      protein 1 unique region (VP1u) contains an N-terminal receptor-binding domain
      (RBD), which mediates the uptake of the virus into cells of the erythroid
      lineage. To further investigate the role of the RBD in connection with a B19V
      unrelated capsid, we chemically coupled the VP1u of B19V to the bacteriophage MS2
      capsid and tested the internalization capacity of the bioconjugate on permissive
      cells. In comparison, we studied the cellular uptake and infection of B19V along
      the erythroid differentiation. The results showed that the MS2-VP1u bioconjugate
      mimicked the specific internalization of the native B19V into erythroid precursor
      cells, which further coincides with the restricted infection profile. The
      successful mimicry of B19V uptake demonstrates that the RBD in the VP1u is
      sufficient for the endocytosis of the viral capsid. Furthermore, the recombinant
      VP1u competed with B19V uptake into permissive cells, thus excluding a
      significant alternative uptake mechanism by other receptors. Strikingly, the VP1u
      receptor appeared to be expressed only on erythropoietin-dependent erythroid
      differentiation stages that also provide the necessary intracellular factors for
      a productive infection. Taken together, these findings suggest that the VP1u
      binds to a yet-unknown erythroid-specific cellular receptor and thus restricts
      the virus entry to permissive cells.

PMID- 27690082
TI  - Structural Maturation of HIV-1 Reverse Transcriptase-A Metamorphic Solution to
      Genomic Instability.
AB  - Human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT)-a critical
      enzyme of the viral life cycle-undergoes a complex maturation process, required
      so that a pair of p66 precursor proteins can develop conformationally along
      different pathways, one evolving to form active polymerase and ribonuclease H
      (RH) domains, while the second forms a non-functional polymerase and a
      proteolyzed RH domain. These parallel maturation pathways rely on the structural
      ambiguity of a metamorphic polymerase domain, for which the sequence-structure
      relationship is not unique. Recent nuclear magnetic resonance (NMR) studies
      utilizing selective labeling techniques, and structural characterization of the
      p66 monomer precursor have provided important insights into the details of this
      maturation pathway, revealing many aspects of the three major steps involved: (1)
      domain rearrangement; (2) dimerization; and (3) subunit-selective RH domain
      proteolysis. This review summarizes the major structural changes that occur
      during the maturation process. We also highlight how mutations, often viewed
      within the context of the mature RT heterodimer, can exert a major influence on
      maturation and dimerization. It is further suggested that several steps in the RT
      maturation pathway may provide attractive targets for drug development.

PMID- 27690084
TI  - Emergence of a Latent Indian Cassava Mosaic Virus from Cassava Which Recovered
      from Infection by a Non-Persistent Sri Lankan Cassava Mosaic Virus.
AB  - The major threat for cassava cultivation on the Indian subcontinent is cassava
      mosaic disease (CMD) caused by cassava mosaic geminiviruses which are bipartite
      begomoviruses with DNA A and DNA B components. Indian cassava mosaic virus (ICMV)
      and Sri Lankan cassava mosaic virus (SLCMV) cause CMD in India. Two isolates of
      SLCMV infected the cassava cultivar Sengutchi in the fields near Malappuram and
      Thiruvananthapuram cities of Kerala State, India. The Malappuram isolate was
      persistent when maintained in the Madurai Kamaraj University (MKU, Madurai, Tamil
      Nadu, India) greenhouse, whereas the Thiruvananthapuram isolate did not persist.
      The recovered cassava plants with the non-persistent SLCMV, which were maintained
      vegetative in quarantine in the University of Basel (Basel, Switzerland)
      greenhouse, displayed re-emergence of CMD after a six-month period.
      Interestingly, these plants did not carry SLCMV but carried ICMV. It is
      interpreted that the field-collected, SLCMV-infected cassava plants were co
      infected with low levels of ICMV. The loss of SLCMV in recovered cassava plants,
      under greenhouse conditions, then facilitated the re-emergence of ICMV. The
      partial dimer clones of the persistent and non-persistent isolates of SLCMV and
      the re-emerged isolate of ICMV were infective in Nicotiana benthamiana upon
      agroinoculation. Studies on pseudo-recombination between SLCMV and ICMV in N.
      benthamiana provided evidence for trans-replication of ICMV DNA B by SLCMV DNA A.

PMID- 27690085
TI  - Enhanced Replication of Hepatitis E Virus Strain 47832c in an A549-Derived
      Subclonal Cell Line.
AB  - Hepatitis E virus (HEV) is a human pathogen with increasing importance. The lack
      of efficient cell culture systems hampers systematic studies on its replication
      cycle, virus neutralization and inactivation. Here, several cell lines were
      inoculated with the HEV genotype 3c strain 47832c, previously isolated from a
      chronically infected transplant patient. At 14 days after inoculation the highest
      HEV genome copy numbers were found in A549 cells, followed by PLC/PRF/5 cells,
      whereas HepG2/C3A, Huh-7 Lunet BLR and MRC-5 cells only weakly supported virus
      replication. Inoculation of A549-derived subclone cell lines resulted in most
      cases in reduced HEV replication. However, the subclone A549/D3 was susceptible
      to lower virus concentrations and resulted in higher virus yields as compared to
      parental A549 cells. Transcriptome analysis indicated a downregulation of genes
      for carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 5 and 6,
      and an upregulation of the syndecan 2 (SDC2) gene in A549/D3 cells compared to
      A549 cells. However, treatment of A549/D3 cells or A549 cells with CEACAM- or
      syndecan 2-specific antisera did not influence HEV replication. The results show
      that cells supporting more efficient HEV replication can be selected from the
      A549 cell line. The specific mechanisms responsible for the enhanced replication
      remain unknown.

PMID- 27690087
TI  - A Trypsin Inhibitor from Tamarind Reduces Food Intake and Improves Inflammatory
      Status in Rats with Metabolic Syndrome Regardless of Weight Loss.
AB  - Trypsin inhibitors are studied in a variety of models for their anti-obesity and
      anti-inflammatory bioactive properties. Our group has previously demonstrated the
      satietogenic effect of tamarind seed trypsin inhibitors (TTI) in eutrophic mouse
      models and anti-inflammatory effects of other trypsin inhibitors. In this study,
      we evaluated TTI effect upon satiety, biochemical and inflammatory parameters in
      an experimental model of metabolic syndrome (MetS). Three groups of n = 5 male
      Wistar rats with obesity-based MetS received for 10 days one of the following:
      (1) Cafeteria diet; (2) Cafeteria diet + TTI (25 mg/kg); and (3) Standard diet.
      TTI reduced food intake in animals with MetS. Nevertheless, weight gain was not
      different between studied groups. Dyslipidemia parameters were not different with
      the use of TTI, only the group receiving standard diet showed lower very low
      density lipoprotein (VLDL) and triglycerides (TG) (Kruskal-Wallis, p < 0.05).
      Interleukin-6 (IL-6) production did not differ between groups. Interestingly,
      tumor necrosis factor-alpha (TNF-alpha) was lower in animals receiving TTI. Our
      results corroborate the satietogenic effect of TTI in a MetS model. Furthermore,
      we showed that TTI added to a cafeteria diet may decrease inflammation regardless
      of weight loss. This puts TTI as a candidate for studies to test its
      effectiveness as an adjuvant in MetS treatment.

PMID- 27690088
TI  - The Growth of SGC-7901 Tumor Xenografts Was Suppressed by Chinese Bayberry
      Anthocyanin Extract through Upregulating KLF6 Gene Expression.
AB  - To investigate the antitumor effect of anthocyanins extracted from Chinese
      bayberry fruit (Myrica rubra Sieb. et Zucc.), a nude mouse tumor xenograft model
      was established. Treatments with C3G (cyanidin-3-glucoside, an anthocyanin)
      significantly suppressed the growth of SGC-7901 tumor xenografts in a dose
      dependent manner. Immunohistochemical staining showed a significant increase in
      p21 expression, indicating that the cell cycle of tumor xenografts was inhibited.
      qPCR screening showed that C3G treatment up-regulated the expression of the KLF6
      gene, which is an important tumor suppressor gene inactivated in many human
      cancers. Western blot showed that C3G treatments markedly increased KLF6 and p21
      protein levels, inhibited CDK4 and Cyclin D1 expression, but did not notably
      change the expression of p53. These results indicated that KLF6 up-regulates p21
      in a p53-independent manner and significantly reduces tumor proliferation. This
      study provides important information for the possible mechanism of C3G-induced
      antitumor activity against gastric adenocarcinoma in vivo.

PMID- 27690090
TI  - A Courageous Report on the Management of Malnutrition.
AB  - Globally, childhood undernutrition continues to be a major public health concern,
      with an estimated 165 million children classified as stunted and 51.5 million
      suffering from acute malnutrition.[...].

PMID- 27690089
TI  - Immune-Enhancing Effects of a High Molecular Weight Fraction of Cynanchum
      wilfordii Hemsley in Macrophages and Immunosuppressed Mice.
AB  - The objective of this study was to investigate the immune-enhancing activity of a
      high molecular weight fraction (HMF) of Cynanchum wilfordii in RAW 264.7
      macrophages and the cyclophosphamide (CYC)-induced mouse model of
      immunosuppression. To identify the bioactive substances of HMF, a crude
      polysaccharide (HMFO) was obtained and treated with sodium periodate (an
      oxidation agent) or digested with protease. In macrophages, HMF treatment
      enhanced the production of nitric oxide (NO) and cytokines (tumor necrosis factor
      alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 1beta (IL-1beta)), as
      well as phagocytic ability. In CYC-immunosuppressed mice, HMF improved relative
      spleen and thymus weights, natural killer (NK) cell activity, and splenic
      lymphocyte proliferation. These increases in NO and cytokines were mediated by up
      regulation of nuclear factor kappa B (NF-kappaB) and mitogen-activated protein
      kinase (MAPK) signaling pathways. Periodate treatment, but not protease
      treatment, decreased the immune-enhancing activity of HMFO, suggesting that
      polysaccharides are the active ingredients in C. wilfordii extract.

PMID- 27690086
TI  - Multi-Omics Studies towards Novel Modulators of Influenza A Virus-Host
      Interaction.
AB  - Human influenza A viruses (IAVs) cause global pandemics and epidemics. These
      viruses evolve rapidly, making current treatment options ineffective. To identify
      novel modulators of IAV-host interactions, we re-analyzed our recent
      transcriptomics, metabolomics, proteomics, phosphoproteomics, and
      genomics/virtual ligand screening data. We identified 713 potential modulators
      targeting 199 cellular and two viral proteins. Anti-influenza activity for 48 of
      them has been reported previously, whereas the antiviral efficacy of the 665
      remains unknown. Studying anti-influenza efficacy and immuno/neuro-modulating
      properties of these compounds and their combinations as well as potential viral
      and host resistance to them may lead to the discovery of novel modulators of IAV
      host interactions, which might be more effective than the currently available
      anti-influenza therapeutics.

PMID- 27690091
TI  - Intakes of Folate and Vitamin B12 and Biomarkers of Status in the Very Old: The
      Newcastle 85+ Study.
AB  - Very old adults are at increased risk of folate and vitamin B12 deficiencies due
      to reduced food intake and gastrointestinal absorption. The main aim was to
      determine the association between folate and vitamin B12 intake from total diets
      and food groups, and status. Folate or vitamin B12 intakes (2 * 24 h multiple
      pass recalls) and red blood cell (RBC) folate or plasma vitamin B12
      (chemiluminescence immunoassays) concentrations were available at baseline for
      731 participants aged 85 from the Newcastle 85+ Study (North-East England).
      Generalized additive and binary logistic models estimated the associations
      between folate and vitamin B12 intakes from total diets and food groups, and RBC
      folate and plasma B12. Folate intake from total diets and cereal and cereal
      products was strongly associated with RBC folate (p < 0.001). Total vitamin B12
      intake was weakly associated with plasma vitamin B12 (p = 0.054) but those with
      higher intakes from total diets or meat and meat products were less likely to
      have deficient status. Women homozygous for the FUT2 G allele had higher
      concentrations of plasma vitamin B12. Cereals and cereal products are a very
      important source of folate in the very old. Higher intakes of folate and vitamin
      B12 lower the risk of "inadequate" status.

PMID- 27690092
TI  - Food and Nutrient Intake among 12-Month-Old Norwegian-Somali and Norwegian-Iraqi
      Infants.
AB  - The aim of the present paper was to describe food and nutrient intake among 12
      month-old Norwegian-Somali and Norwegian-Iraqi infants, with a focus on iron and
      vitamin D intake. A cross-sectional survey was conducted from August 2013 through
      September 2014. Eighty-nine mothers/infants of Somali origin and 77
      mothers/infants of Iraqi origin residing in Eastern Norway participated in the
      study. Data were collected using two 24-h multiple-pass recalls. Forty percent of
      the Norwegian-Somali infants and 47% of the Norwegian-Iraqi infants were
      breastfed at 12 months of age (p = 0.414). Median energy percentages (E%) from
      protein, fat and carbohydrates were within the recommended intake ranges, except
      the level of saturated fats (12-13 E%). Median intakes of almost all
      micronutrients were above the recommended daily intakes. Most of the infants
      consumed iron-enriched products (81%) and received vitamin D supplements (84%).
      The median intakes of iron and vitamin D were significantly higher among infants
      receiving iron-enriched products and vitamin D supplements compared to infants
      not receiving such products (p < 0.001). The findings indicate that the food and
      nutrient intake of this group of infants in general seems to be in accordance
      with Norwegian dietary recommendations. Foods rich in iron and vitamin D
      supplements were important sources of the infants' intake of iron and vitamin D
      and should continue to be promoted.

PMID- 27690093
TI  - Efficacy of Synbiotics in Patients with Slow Transit Constipation: A Prospective
      Randomized Trial.
AB  - Synbiotic intake may efficiently restore the balance of gut microbiota and
      improve gastrointestinal functions. The aim of the study was to evaluate the
      efficacy of a synbiotic in patients with slow transit constipation. A total of
      100 patients with slow transit constipation were randomized to receive either a
      synbiotic or placebo twice daily for 12 weeks. The primary efficacy endpoints
      were the clinical remission and improvement rates at weeks 4 and 12. Stool
      frequency and consistency, colonic transit time (CTT), evacuation and abdominal
      symptoms, patient assessment of constipation symptoms, gastrointestinal quality
      of-life index scores, satisfaction scores, and adverse events were also
      monitored. The clinical remission rates reached 37.5% at week 4 and 45.8% at week
      12 in the treatment group, compared to 13.3% at week 4 and 16.7% at week 12 in
      the placebo group (p < 0.01 for both comparisons). Over 12 weeks, 64.6% of the
      patients who received the synbiotic experienced clinical improvement, compared to
      29.2% of the patients in the placebo group (p < 0.01). During the intervention
      period, patients who were treated with the synbiotic exhibited increased stool
      frequency, improved stool consistency, decreased CTT, and improved constipation
      related symptoms. This randomized, placebo-controlled trial suggested that
      dietary supplementation with a synbiotic improved evacuation-parameters
      associated symptoms and colonic motility in patients with slow transit
      constipation (STC).

PMID- 27690094
TI  - Amino Acid Composition of Breast Milk from Urban Chinese Mothers.
AB  - Human breast milk (BM) amino acid (AA) composition may be impacted by lactation
      stage or factors related to geographical location. The present cross-sectional
      study is aimed at assessing the temporal changes of BMAA over lactation stages in
      a large cohort of urban mothers in China. Four hundred fifty BM samples,
      collected in three Chinese cities covering eight months of lactation were
      analyzed for free (FAA) and total (TAA) AA by o-phthalaldehyde/
      fluorenylmethylchloroformate (OPA/FMOC) derivatization. Concentrations and
      changes over lactation were aligned with previous reports. Both the sum and the
      individual TAA values significantly decreased during the first periods of
      lactation and then generally leveled off. Leucine and methionine were
      respectively the most and the least abundant indispensable amino acids across all
      the lactation stages, whereas glutamic acid + glutamine (Glx) was the most and
      cystine the least abundant dispensable AA. The contribution of FAA to TAA levels
      was less than 2%, except for free Glx, which was the most abundant FAA. In
      conclusion, the AA composition of the milk from our cohort of urban Chinese
      mothers was comparable to previous studies conducted in other parts of the world,
      suggesting that this is an evolutionary conserved trait largely independent of
      geographical, ethnic, or dietary factors.

PMID- 27690095
TI  - The VITAH Trial-Vitamin D Supplementation and Cardiac Autonomic Tone in Patients
      with End-Stage Kidney Disease on Hemodialysis: A Blinded, Randomized Controlled
      Trial.
AB  - : End-stage kidney disease (ESKD) patients are at increased cardiovascular risk.
      Vitamin D deficiency is associated with depressed heart rate variability (HRV), a
      risk factor depicting poor cardiac autonomic tone and risk of cardiovascular
      death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD
      population. We aimed to determine the effects of oral vitamin D supplementation
      on HRV ((low frequency (LF) to high frequency (HF) spectral ratio (LF:HF)) in
      ESKD patients on hemodialysis. Fifty-six subjects with ESKD requiring
      hemodialysis were recruited from January 2013-March 2015 and randomized 1:1 to
      either conventional (0.25 mcg alfacalcidol plus placebo 3*/week) or intensive
      (0.25 mcg alfacalcidol 3*/week plus 50,000 international units (IU)
      ergocalciferol 1*/week) vitamin D for six weeks. The primary outcome was the
      change in LF:HF. There was no difference in LF:HF from baseline to six weeks for
      either vitamin D treatment (conventional: p = 0.9 vs. baseline; intensive: p =
      0.07 vs. baseline). However, participants who remained vitamin D-deficient (25
      hydroxyvitamin D < 20 ng/mL) after treatment demonstrated an increase in LF:HF
      (conventional: n = 13, ?LF:HF: 0.20 +/- 0.06, p < 0.001 vs. insufficient and
      sufficient vitamin D groups; intensive: n = 8: ?LF:HF: 0.15 +/- 0.06, p < 0.001
      vs. sufficient vitamin D group). Overall, six weeks of conventional or intensive
      vitamin D only augmented LF:HF in ESKD subjects who remained vitamin D-deficient
      after treatment. Our findings potentially suggest that while activated vitamin D,
      with or without additional nutritional vitamin D, does not appear to improve
      cardiac autonomic tone in hemodialysis patients with insufficient or sufficient
      baseline vitamin D levels, supplementation in patients with severe vitamin D
      deficiency may improve cardiac autonomic tone in this higher risk sub-population
      of ESKD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01774812.

PMID- 27690096
TI  - Effects of n-3 PUFAs on Intestinal Mucosa Innate Immunity and Intestinal
      Microbiota in Mice after Hemorrhagic Shock Resuscitation.
AB  - n-3 polyunsaturated fatty acids (PUFAs) can improve the function of the
      intestinal barrier after damage from ischemia-reperfusion or hemorrhagic shock
      resuscitation (HSR). However, the effects of n-3 PUFAs on intestinal microbiota
      and the innate immunity of the intestinal mucosa after HSR remain unclear. In the
      present study, 40 C57BL/6J mice were randomly assigned to five groups: control,
      sham, HSR, HSR + n-3 PUFAs and HSR + n-6 PUFAs. Mice were sacrificed 12 h after
      HSR. Liver, spleen, mesenteric lymph nodes and terminal ileal tissues were
      collected. Intestinal mucosae were scraped aseptically. Compared with the HSR
      group, the number of goblet cells increased, expression of mucin 2 was restored
      and disturbed intestinal microbiota were partly stabilized in the PUFA
      administered groups, indicating that both n-3 and n-6 PUFAs reduced
      overproliferation of Gammaproteobacteria while promoting the growth of
      Bacteroidetes. Notably, n-3 PUFAs had an advantage over n-6 PUFAs in improving
      ileal tissue levels of lysozyme after HSR. Thus, PUFAs, especially n-3 PUFAs,
      partly improved the innate immunity of intestinal mucosa in mice after HSR. These
      findings suggest a clinical rationale for providing n-3 PUFAs to patients
      recovering from ischemia-reperfusion.

PMID- 27690097
TI  - Vitamin D Intake and Serum 25-Hydroxyvitamin D Levels in Korean Adults: Analysis
      of the 2009 Korea National Health and Nutrition Examination Survey (KNHANES IV-3)
      Using a Newly Established Vitamin D Database.
AB  - Vitamin D is important for maintaining bone health and may prevent various
      diseases (i.e., cardiovascular disease and cancer). The aim of this study was to
      estimate vitamin D intakes of Korean adults using the Korea National Health and
      Nutrition Examination Survey (KNHANES, 2009) data and a newly established vitamin
      D database. KNHANES (2009) participants (n = 4541; 2021 men; 2520 women) aged
      >=20 years were included. Dietary vitamin D intake, serum 25-hydroxyvitamin D
      (25(OH)D), and the relationship between vitamin D intake and serum 25(OH)D were
      evaluated. In men and women, vitamin D intakes were 4.00 +/- 0.17 ug/day and 2.6
      +/- 0.1 ug/day respectively, and serum 25(OH)D concentrations were 19.78 +/- 0.33
      ng/mL and 17.10 +/- 0.26 ng/mL respectively. Serum 25(OH)D concentrations of men
      aged <50 years and women aged >20 years were under 20 ng/mL. After adjusting for
      confounding factors, the positive relationship between vitamin D intake and serum
      25(OH)D was observed in total subjects (p < 0.05), excluding participants >=50
      years old. The main food sources for vitamin D among Korean adults were
      fish/shellfish (71.34%) and egg (14.89%). Korean adults should increase their
      serum 25(OH)D concentrations by increasing vitamin D intake.

PMID- 27690098
TI  - BmP02 Atypically Delays Kv4.2 Inactivation: Implication for a Unique Interaction
      between Scorpion Toxin and Potassium Channel.
AB  - BmP02, a short-chain peptide with 28 residues from the venom of Chinese scorpion
      Buthus martensi Karsch, has been reported to inhibit the transient outward
      potassium currents (Ito) in rat ventricular muscle cells. However, it remains
      unclear whether BmP02 modulates the Kv4.2 channel, one of the main contributors
      to Ito. The present study investigated the effects of BmP02 on Kv4.2 kinetics and
      its underlying molecular mechanism. The electrophysiological recordings showed
      that the inactivation of Kv4.2 expressed in HEK293T cells was significantly
      delayed by BmP02 in a dose-response manner with EC50 of ~850 nM while the peak
      current, activation and voltage-dependent inactivation of Kv4.2 were not
      affected. Meanwhile, the recovery from inactivation of Kv4.2 was accelerated and
      the deactivation was slowed after the application of BmP02. The site-directed
      mutagenesis combined with computational modelling identified that K347 and K353,
      located in the turret motif of the Kv4.2, and E4/E5, D20/D21 in BmP02 are key
      residues to interact with BmP02 through electrostatic force. These findings not
      only reveal a novel interaction between Kv4.2 channel and its peptidyl modulator,
      but also provide valuable information for design of highly-selective Kv4.2
      modulators.

PMID- 27690099
TI  - Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related
      Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin
      Secretions.
AB  - Bradykinin-related peptides (BRPs) are one of the most extensively studied frog
      secretions-derived peptide families identified from many amphibian species. The
      diverse primary structures of BRPs have been proven essential for providing
      valuable information in understanding basic mechanisms associated with drug
      modification. Here, we isolated, identified and characterized a dodeca-BRP (RAP
      L1, T6-BK), with primary structure RAPLPPGFTPFR, from the skin secretions of
      Chinese large odorous frogs, Odorrana livida. This novel peptide exhibited a dose
      dependent contractile property on rat bladder and rat ileum, and increased the
      contraction frequency on rat uterus ex vivo smooth muscle preparations; it also
      showed vasorelaxant activity on rat tail artery smooth muscle. In addition, the
      analogue RAP-L1, T6, L8-BK completely abolished these effects on selected rat
      smooth muscle tissues, whilst it showed inhibition effect on bradykinin-induced
      rat tail artery relaxation. By using canonical antagonist for bradykinin B1 or B2
      type receptors, we found that RAP-L1, T6-BK -induced relaxation of the arterial
      smooth muscle was very likely to be modulated by B2 receptors. The analogue RAP
      L1, T6, L8-BK further enhanced the bradykinin inhibitory activity only under the
      condition of co-administration with HOE140 on rat tail artery, suggesting a
      synergistic inhibition mechanism by which targeting B2 type receptors.

PMID- 27690100
TI  - Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin
      Systems.
AB  - Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that
      targets an essential cellular process) and an antitoxin that neutralises or
      suppresses the deleterious effect of the toxin. Based on the molecular nature of
      the toxin and antitoxin components, TA systems are categorised into different
      types. Type III TA systems, the focus of this review, are composed of a toxic
      endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted
      configuration. Bioinformatic analysis shows that the Type III systems can be
      classified into subtypes. These TA systems were originally discovered through a
      phage resistance phenotype arising due to a process akin to an altruistic
      suicide; the phenomenon of abortive infection. Some Type III TA systems are
      bifunctional and can stabilise plasmids during vegetative growth and sporulation.
      Features particular to Type III systems are explored here, emphasising some of
      the characteristics of the RNA antitoxin and how these may affect the co
      evolutionary relationship between toxins and cognate antitoxins in their
      quaternary structures. Finally, an updated analysis of the distribution and
      diversity of these systems are presented and discussed.

PMID- 27690101
TI  - Effects of Citric and Lactic Acid on the Reduction of Deoxynivalenol and Its
      Derivatives in Feeds.
AB  - Exposure to mycotoxin-contaminated feeds represents a serious health risk. This
      has necessitated the need for the establishment of practical methods for
      mycotoxin decontamination. This study investigated the effects of citric acid
      (CA) and lactic acid (LA) on common trichothecene mycotoxins in feeds
      contaminated with Fusarium mycotoxins. Contaminated feed samples were processed
      either with 5% CA or 5% LA solutions in a ratio of 1:1.2 (w/v) for 5, 24, or 48
      h, and analyzed for multiple mycotoxin metabolites using a liquid chromatography
      tandem mass spectrometric method. The analyses showed that treating the feed with
      CA and LA lowered the concentration of deoxynivalenol (DON), whereby 5% LA
      lowered the original DON concentration in the contaminated feed samples by half,
      irrespective of the processing time. Similar lowering effects were observed for
      the concentrations of 15Ac-DON, 5-hydroxyculmorin, and sambucinol. The
      concentration of nivalenol was only lowered by the LA treatment. In contrast, CA
      and LA treatments showed no or only small effects on the concentration of several
      mycotoxins and their derivatives, including zearalenone, fumonisins, and
      culmorin. In conclusion, the present results indicate that the use of 5%
      solutions of LA and CA might reduce the concentration of common trichothecene
      mycotoxins, especially DON and its derivate 15Ac-DON. However, further research
      is required to determine the effect on overall toxicity and to identify the
      underlying mechanisms.

PMID- 27690103
TI  - Transcript Abundance of Photorhabdus Insect-Related (Pir) Toxin in Manduca sexta
      and Galleria mellonella Infections.
AB  - In this study, we assessed pirAB toxin transcription in Photorhabdus luminescens
      laumondii (strain TT01) (Enterobacteriaceae) by comparing mRNA abundance under in
      vivo and in vitro conditions. In vivo assays considered both natural and forced
      infections with two lepidopteran hosts: Galleria mellonella and Manduca sexta.
      Three portals of entry were utilized for the forced infection assays: (a)
      integument; (b) the digestive route (via mouth and anus); and (c) the tracheal
      route (via spiracles). We also assessed plu4093-2 transcription during the course
      of a natural infection; this is when the bacteria are delivered by
      Heterorhabditis bacteriophora nematodes. Transcript abundance in G. mellonella
      was higher than in M. sexta at two of the observed time points: 15 and 18 h.
      Expression of pirAB plu4093-2 reached above endogenous control levels at 22 h in
      G. mellonella but not in M. sexta. Overall, pirAB plu4093-2 transcripts were not
      as highly expressed in M. sexta as in G. mellonella, from 15 to 22 h. This is the
      first study to directly compare pirAB plu4093-2 toxin transcript production
      considering different portals of entry.

PMID- 27690104
TI  - Translating into Practice Cancer Patients' Views on Do-Not-Resuscitate Decision
      Making.
AB  - Do-not-resuscitate (DNR) orders are necessary if resuscitation, the default
      option in hospitals, should be avoided because a patient is known to be dying and
      attempted resuscitation would be inappropriate. To avoid inappropriate
      resuscitation at night, if no DNR order has been recorded, after-hours medical
      staff are often asked to have a DNR discussion with patients whose condition is
      deteriorating, but with whom they are unfamiliar. Participants in two qualitative
      studies of cancer patients' views on how to present DNR discussions recognized
      that such patients are at different stages of understanding of their situation
      and may not be ready for a DNR discussion; therefore, a one-policy-fits-all
      approach was thought to be inappropriate. To formulate a policy that incorporates
      the patient's views, we propose that a standard form which mandates a DNR
      discussion is replaced by a "blank sheet" with instructions to record the
      progress of the discussion with the patient, and a medical recommendation for a
      DNR decision to guide the nursing staff in case of a cardiac arrest. Such an
      advance care directive would have to honor specifically expressed patient or
      guardian wishes whilst allowing for flexibility, yet would direct nurses or other
      staff so that they can avoid inappropriate cardiopulmonary resuscitation of a
      patient dying of cancer.

PMID- 27690105
TI  - Decreased Expression of KIFC1 in Human Testes with Globozoospermic Defects.
AB  - Globozoospermia is a rare (prevalence of <0.1%) but severe male infertility
      condition. In our previous study, we found that robust KIFC1 immunostaining was
      detected in the human elongating/elongated spermatids during human
      acrosomogenesis. However, the relationship between the decreased expression of
      KIFC1 and human globozoospermia remains largely unknown. Testicular biopsies of
      30 globozoospermia and 30 obstructive azoospermia patients who underwent
      infertility evaluation and treatment were utilized in this study. Reverse
      transcriptase polymerase chain reaction (RT-PCR), Western blots,
      immunohistochemistry, an in vivo model, and intratesticular injection of small
      inhibitory RNA (siRNA) against the Kifc1 gene were employed, and sperm
      abnormalities were evaluated by hematoxylin and eosin (H&E) staining and
      immunocytochemistry. We revealed that the testicular level of KIFC1 mRNA in
      globozoospermia was significantly reduced compared with that in obstructive
      azoospermia, and the KIFC1 protein was barely detectable in testicular specimens
      in 30% (9 of 30) of patients with globozoospermia. Furthermore, knockdown of the
      Kifc1 gene in mice increased the percentage of sperm with globozoospermic defects
      (26.5%). Decreased KIFC1 expression was mainly observed in the testes of patients
      with globozoospermia at the spermatid stage, which may be useful for counseling
      and management of such patients.

PMID- 27690102
TI  - Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet
      Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites.
AB  - Snake venom metalloproteases, in addition to their contribution to the digestion
      of the prey, affect various physiological functions by cleaving specific
      proteins. They exhibit their activities through activation of zymogens of
      coagulation factors, and precursors of integrins or receptors. Based on their
      structure-function relationships and mechanism of action, we have defined
      classification and nomenclature of functional sites of proteases. These
      metalloproteases are useful as research tools and in diagnosis and treatment of
      various thrombotic and hemostatic conditions. They also contribute to our
      understanding of molecular details in the activation of specific factors involved
      in coagulation, platelet aggregation and matrix biology. This review provides a
      ready reference for metalloproteases that interfere in blood coagulation,
      fibrinolysis and platelet aggregation.

PMID- 27690106
TI  - Impact of the Autism-Associated Long Noncoding RNA MSNP1AS on Neuronal
      Architecture and Gene Expression in Human Neural Progenitor Cells.
AB  - We previously identified the long noncoding RNA (lncRNA) MSNP1AS (moesin
      pseudogene 1, antisense) as a functional element revealed by genome wide
      significant association with autism spectrum disorder (ASD). MSNP1AS expression
      was increased in the postmortem cerebral cortex of individuals with ASD and
      particularly in individuals with the ASD-associated genetic markers on chromosome
      5p14.1. Here, we mimicked the overexpression of MSNP1AS observed in postmortem
      ASD cerebral cortex in human neural progenitor cell lines to determine the impact
      on neurite complexity and gene expression. ReNcell CX and SK-N-SH were
      transfected with an overexpression vector containing full-length MSNP1AS.
      Neuronal complexity was determined by the number and length of neuronal
      processes. Gene expression was determined by strand-specific RNA sequencing.
      MSNP1AS overexpression decreased neurite number and neurite length in both human
      neural progenitor cell lines. RNA sequencing revealed changes in gene expression
      in proteins involved in two biological processes: protein synthesis and chromatin
      remodeling. These data indicate that overexpression of the ASD-associated lncRNA
      MSNP1AS alters the number and length of neuronal processes. The mechanisms by
      which MSNP1AS overexpression impacts neuronal differentiation may involve protein
      synthesis and chromatin structure. These same biological processes are also
      implicated by rare mutations associated with ASD, suggesting convergent
      mechanisms.

PMID- 27690108
TI  - Cloning and Expression Analysis of MEP Pathway Enzyme-encoding Genes in Osmanthus
      fragrans.
AB  - The 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway is responsible for the
      biosynthesis of many crucial secondary metabolites, such as carotenoids,
      monoterpenes, plastoquinone, and tocopherols. In this study, we isolated and
      identified 10 MEP pathway genes in the important aromatic plant sweet osmanthus
      (Osmanthus fragrans). Multiple sequence alignments revealed that 10 MEP pathway
      genes shared high identities with other reported proteins. The genes showed
      distinctive expression profiles in various tissues, or at different flower stages
      and diel time points. The qRT-PCR results demonstrated that these genes were
      highly expressed in inflorescences, which suggested a tissue-specific transcript
      pattern. Our results also showed that OfDXS1, OfDXS2, and OfHDR1 had a clear
      diurnal oscillation pattern. The isolation and expression analysis provides a
      strong foundation for further research on the MEP pathway involved in gene
      function and molecular evolution, and improves our understanding of the molecular
      mechanism underlying this pathway in plants.

PMID- 27690107
TI  - Modeling Fragile X Syndrome Using Human Pluripotent Stem Cells.
AB  - Fragile X syndrome (FXS) is the most common heritable form of cognitive
      impairment. It results from a loss-of-function mutation by a CGG repeat expansion
      at the 5' untranslated region of the X-linked fragile X mental retardation 1
      (FMR1) gene. Expansion of the CGG repeats beyond 200 copies results in protein
      deficiency by leading to aberrant methylation of the FMR1 promoter and the switch
      from active to repressive histone modifications. Additionally, the CGGs become
      increasingly unstable, resulting in high degree of variation in expansion size
      between and within tissues of affected individuals. It is still unclear how the
      FMR1 protein (FMRP) deficiency leads to disease pathology in neurons. Nor do we
      know the mechanisms by which the CGG expansion results in aberrant DNA
      methylation, or becomes unstable in somatic cells of patients, at least in part
      due to the lack of appropriate animal or cellular models. This review summarizes
      the current contribution of pluripotent stem cells, mutant human embryonic stem
      cells, and patient-derived induced pluripotent stem cells to disease modeling of
      FXS for basic and applied research, including the development of new therapeutic
      approaches.

PMID- 27690109
TI  - Metabolic Genes within Cyanophage Genomes: Implications for Diversity and
      Evolution.
AB  - Cyanophages, a group of viruses specifically infecting cyanobacteria, are
      genetically diverse and extensively abundant in water environments. As a result
      of selective pressure, cyanophages often acquire a range of metabolic genes from
      host genomes. The host-derived genes make a significant contribution to the
      ecological success of cyanophages. In this review, we summarize the host-derived
      metabolic genes, as well as their origin and roles in cyanophage evolution and
      important host metabolic pathways, such as the light-dependent reactions of
      photosynthesis, the pentose phosphate pathway, nutrient acquisition and
      nucleotide biosynthesis. We also discuss the suitability of the host-derived
      metabolic genes as potential diagnostic markers for the detection of genetic
      diversity of cyanophages in natural environments.

PMID- 27690111
TI  - Prey-Mediated Effects of Drought on the Consumption Rates of Coccinellid
      Predators of Elatobium abietinum.
AB  - Climate change in the UK is predicted to cause an increase in summer drought
      events. Elatobium abietinum is an important pest of Sitka spruce (Picea
      sitchensis), causing defoliation of trees, and is predicted to become more
      abundant in response to climatic change, reducing spruce productivity.
      Populations are also moderated by invertebrate predators, though the extent to
      which this might be modified under a changing climate is unclear. Elatobium
      abietinum is preyed upon by the coccinellid species Aphidecta obliterata (a
      spruce specialist) and Adalia bipunctata (a generalist), populations of which
      naturally occur in spruce plantations. This study sought to investigate the
      effect of different intensities and frequencies of drought on the consumption
      rate of the aphids by the two coccinellids. In Petri dish trials, severe drought
      stress increased the consumption rates of 3rd instar aphids by both adult and
      larval coccinellids. Moderate intermittent stress tended to result in a reduced
      consumption rate for larval coccinellids only, suggesting an age-dependent
      response. The findings of this study suggest that, under drought conditions, a
      prey-mediated effect on predator consumption, and, therefore, biocontrol
      efficacy, is likely, with drought intensity and frequency playing an important
      role in determining the nature of the response.

PMID- 27690110
TI  - Genome-Wide Identification, Characterization and Expression Profiling of ADF
      Family Genes in Solanum lycopersicum L.
AB  - The actin depolymerizing factor (ADF) proteins have growth, development, defense
      related and growth regulatory functions in plants. The present study used genome
      wide analysis to investigate ADF family genes in tomato. Eleven tomato ADF genes
      were identified and differential expression patterns were found in different
      organs. SlADF6 was preferentially expressed in roots, suggesting its function in
      root development. SlADF1, SlADF3 and SlADF10 were predominately expressed in the
      flowers compared to the other organs and specifically in the stamen compared to
      other flower parts, indicating their potential roles in pollen development. The
      comparatively higher expression of SlADF3 and SlADF11 at early fruit
      developmental stages might implicate them in determining final fruit size. SlADF5
      and SlADF8 had relatively higher levels of expression five days after the breaker
      stage of fruit development, suggesting their possible role in fruit ripening.
      Notably, six genes were induced by cold and heat, seven by drought, five by NaCl,
      and four each by abscisic acid (ABA), jasmonic acid (JA) and wounding treatments.
      The differential expression patterns of the SlADF genes under different types of
      stresses suggested their function in stress tolerance in tomato plants. Our
      results will be helpful for the functional characterization of ADF genes during
      organ and fruit development of tomato under different stresses.

PMID- 27690112
TI  - Research Contributing to Improvements in Controlling Florida's Mosquitoes and
      Mosquito-borne Diseases.
AB  - Research on mosquitoes and mosquito-borne diseases has contributed to
      improvements in providing effective, efficient, and environmentally proper
      mosquito control. Florida has benefitted from several research accomplishments
      that have increased the state's mosquito control capabilities. Research with
      Florida's mosquitoes has resulted in the development of ecologically sound
      management of mosquito impoundments on Florida's east coast. This strategy,
      called Rotational Impoundment Management (RIM), has improved the ability to
      target the delivery of pesticides and has helped to reduce non-target effects and
      environmental damage. Research has led to the development of an arbovirus
      surveillance system which includes sentinel chicken surveillance, real time use
      of environmental contributing factors like meteorology and hydrology to target
      mosquito control, as well as public health efforts to mitigate disease outbreaks
      to areas with risk of disease. These research driven improvements have provided
      substantial benefits to all of Florida. More research is needed to meet the
      future challenges to reduce emerging pathogens like Zika virus and the
      consequences of environmental changes like global climate change that are likely
      to influence the effects of mosquito-borne pathogens on human health and well
      being.

PMID- 27690113
TI  - Periodic Physical Disturbance: An Alternative Method for Controlling Sitophilus
      zeamais (Maize Weevil) Infestation.
AB  - Sitophilus zeamais Motschulsky is the most important insect pest of stored maize
      in tropical regions. The objective of this study was to determine the
      practicality of periodic physical disturbance on S. zeamais mortality and its
      adoption by smallholder farmers in developing countries. In this experiment,
      treatments and control were arranged in a randomized block design with three
      replications and three storage times in three regions of Tanzania. Region was
      used as the blocking variable. A total of 108 clean 20-L plastic containers were
      each loaded with 10 kg of fresh white dent corn and 0.50 kg of maize infested
      with S. zeamais. For the treatment, containers were disturbed twice a day,
      whereas for the controls the containers were not disturbed until the end of
      storage. The overall mortality rate (%) after 30, 60, and 90 days of storage were
      88%, 96%, and 98%, respectively. A statistically significant difference (p <
      0.05) was observed for the number of live S. zeamais between the control and
      experimental treatments. Additionally, the number of live S. zeamais in the
      treatment significantly decreased as storage time increased. This study shows the
      potential of a feasible, simple, affordable, and effective method of protecting
      maize grain for small-holder farmers in developing countries without using
      chemicals.

PMID- 27690114
TI  - Long-Term Engagement in Formal Volunteering and Well-Being: An Exploratory Indian
      Study.
AB  - Sustained engagement in volunteering and its correlates have been examined in
      many studies across the globe. However, there is a dearth of research that
      explores the perspectives of long-term formal volunteers on the nature of changes
      perceived in oneself as a result of volunteering. Moreover, the linkages between
      psychological well-being and volunteering have been insufficiently explored. The
      present study was aimed at addressing these gaps. A heterogeneous sample of 20
      long-term formal volunteer engaged in volunteering across different voluntary
      organisations in a southern metropolitan Indian city formed the primary sample
      for the study. In addition, a group of 21 short-term volunteers, matched on age,
      income and gender, was utilised for comparison with long-term volunteers on well
      being indices. A semi structured interview schedule was used to explore self
      perceived changes attributable to volunteering experience. In addition, a few
      standardised measures were used to comprehensively assess subjective well-being
      and psychological well-being. The interview data provided rich descriptions of
      perceived positive changes in self across cognitive, behavioral and emotional
      domains. Mirroring these patterns, the quantitative analyses indicated that long
      term volunteers experienced higher levels of psychological well-being (sense of
      mastery and competence, self-acceptance and sense of engagement and growth) than
      short-term volunteers. The potential mechanisms involved in beneficial outcomes
      of long-term volunteering and implications for further research are highlighted.

PMID- 27690115
TI  - Morphology of Donor and Recipient Nerves Utilised in Nerve Transfers to Restore
      Upper Limb Function in Cervical Spinal Cord Injury.
AB  - Loss of hand function after cervical spinal cord injury (SCI) impacts heavily on
      independence. Multiple nerve transfer surgery has been applied successfully after
      cervical SCI to restore critical arm and hand functions, and the outcome depends
      on nerve integrity. Nerve integrity is assessed indirectly using muscle strength
      testing and intramuscular electromyography, but these measures cannot show the
      manifestation that SCI has on the peripheral nerves. We directly assessed the
      morphology of nerves biopsied at the time of surgery, from three patients within
      18 months post injury. Our objective was to document their morphologic features.
      Donor nerves included teres minor, posterior axillary, brachialis, extensor carpi
      radialis brevis and supinator. Recipient nerves included triceps, posterior
      interosseus (PIN) and anterior interosseus nerves (AIN). They were fixed in
      glutaraldehyde, processed and embedded in Araldite Epon for light microscopy.
      Eighty percent of nerves showed abnormalities. Most common were myelin thickening
      and folding, demyelination, inflammation and a reduction of large myelinated axon
      density. Others were a thickened perineurium, oedematous endoneurium and Renaut
      bodies. Significantly, very thinly myelinated axons and groups of unmyelinated
      axons were observed indicating regenerative efforts. Abnormalities exist in both
      donor and recipient nerves and they differ in appearance and aetiology. The
      abnormalities observed may be preventable or reversible.

PMID- 27690116
TI  - Prenatal Ethanol Exposure and Whisker Clipping Disrupt Ultrasonic Vocalizations
      and Play Behavior in Adolescent Rats.
AB  - Prenatal ethanol exposure can result in social deficits in humans and animals,
      including altered social interaction and poor communication. Rats exposed to
      ethanol prenatally show reduced play fighting, and a combination of prenatal
      ethanol exposure and neonatal whisker clipping further reduces play fighting
      compared with ethanol exposure alone. In this study, we explored whether
      expression of hedonic ultrasonic vocalizations (USVs) correlated with the number
      of playful attacks by ethanol-exposed rats, rats subjected to postnatal sensory
      deprivation by whisker clipping or both compared to control animals. In normally
      developing rats, hedonic USVs precede such interactions and correlate with the
      number of play interactions exhibited in dyads. Pregnant Long-Evans rats were fed
      an ethanol-containing liquid diet or a control diet. After birth, male and female
      pups from each litter were randomly assigned to the whisker-clipped or non
      whisker-clipped condition. Animals underwent a social interaction test with a
      normally developing play partner during early or late-adolescence. USVs were
      recorded during play. Prenatal ethanol exposure reduced both play and hedonic
      USVs in early adolescence compared to control rats and persistently reduced
      social play. Interestingly, ethanol exposure, whisker clipping and the
      combination abolished the significant correlation between hedonic USVs and social
      play detected in control rats in early adolescence. This relationship remained
      disrupted in late adolescence only in rats subjected to both prenatal ethanol and
      whisker clipping. Thus, both insults more persistently disrupted the relationship
      between social communication and social play.

PMID- 27690117
TI  - Effect of Experimental Cutaneous Hand Pain on Corticospinal Excitability and
      Short Afferent Inhibition.
AB  - Sensorimotor integration is altered in people with chronic pain. While there is
      substantial evidence that pain interferes with neural activity in primary sensory
      and motor cortices, much less is known about its impact on integrative
      sensorimotor processes. Here, the short latency afferent inhibition (SAI)
      paradigm was used to assess sensorimotor integration in the presence and absence
      of experimental cutaneous heat pain applied to the hand. Ulnar nerve stimulation
      was combined with transcranial magnetic stimulation to condition motor evoked
      potentials (MEPs) in the first dorsal interosseous muscle. Four interstimulus
      intervals (ISI) were tested, based on the latency of the N20 component of the
      afferent sensory volley (N20-5 ms, N20+2 ms, N20+4 ms, N20+10 ms). In the PAIN
      condition, MEPs were smaller compared to the NEUTRAL condition (p = 0.005), and
      were modulated as a function of the ISI (p = 0.012). Post-hoc planned comparisons
      revealed that MEPs at N20+2 and N20+4 were inhibited compared to unconditioned
      MEPs. However, the level of inhibition (SAI) was similar in the PAIN and NEUTRAL
      conditions. This suggests that the interplay between pain and sensorimotor
      integration is not mediated through direct and rapid pathways as assessed by SAI,
      but rather might involve higher-order integrative areas.

PMID- 27690119
TI  - Biosensing with Paper-Based Miniaturized Printed Electrodes-A Modern Trend.
AB  - From the bench-mark work on microfluidics from the Whitesides's group in 2007,
      paper technology has experienced significant growth, particularly regarding
      applications in biomedical research and clinical diagnostics. Besides the
      structural properties supporting microfluidics, other advantageous features of
      paper materials, including their versatility, disposability and low cost, show
      off the great potential for the development of advanced and eco-friendly
      analytical tools. Consequently, paper was quickly employed in the field of
      electrochemical sensors, being an ideal material for producing custom, tailored
      and miniaturized devices. Stencil-, inkjet-, or screen-printing are the
      preferential techniques for electrode manufacturing. Not surprisingly, we
      witnessed a rapid increase in the number of publications on paper based screen
      printed sensors at the turn of the past decade. Among the sensing strategies,
      various biosensors, coupling electrochemical detectors with biomolecules, have
      been proposed. This work provides a critical review and a discussion on the
      future progress of paper technology in the context of miniaturized printed
      electrochemical biosensors.

PMID- 27690118
TI  - Recent Advances in the Fabrication and Application of Screen-Printed
      Electrochemical (Bio)Sensors Based on Carbon Materials for Biomedical, Agri-Food
      and Environmental Analyses.
AB  - This review describes recent advances in the fabrication of electrochemical
      (bio)sensors based on screen-printing technology involving carbon materials and
      their application in biomedical, agri-food and environmental analyses. It will
      focus on the various strategies employed in the fabrication of screen-printed
      (bio)sensors, together with their performance characteristics; the application of
      these devices for the measurement of selected naturally occurring biomolecules,
      environmental pollutants and toxins will be discussed.

PMID- 27690120
TI  - Discrepancy in Vancomycin AUC/MIC Ratio Targeted Attainment Based upon the
      Susceptibility Testing in Staphylococcus aureus.
AB  - This study demonstrated a statistically significant difference in vancomycin
      minimum inhibitory concentration (MIC) for Staphylococcus aureus between a common
      automated system (Vitek 2) and the E-test method in patients with S. aureus
      bloodstream infections. At an area under the serum concentration time curve (AUC)
      threshold of 400 mg?h/L, we would have reached the current Infectious Diseases
      Society of America (IDSA)/American Society of Health System Pharmacists
      (ASHP)/Society of Infectious Diseases Pharmacists (SIDP) guideline suggested
      AUC/MIC target in almost 100% of patients while using the Vitek 2 MIC data;
      however, we could only generate 40% target attainment while using E-test MIC data
      (p < 0.0001). An AUC of 450 mg?h/L or greater was required to achieve 100% target
      attainment using either Vitek 2 or E-test MIC results.

PMID- 27690121
TI  - Resistance to beta-Lactams in Neisseria ssp Due to Chromosomally Encoded
      Penicillin-Binding Proteins.
AB  - Neisseria meningitidis and Neisseria gonorrhoeae are human pathogens that cause a
      variety of life-threatening systemic and local infections, such as meningitis or
      gonorrhoea. The treatment of such infection is becoming more difficult due to
      antibiotic resistance. The focus of this review is on the mechanism of reduced
      susceptibility to penicillin and other beta-lactams due to the modification of
      chromosomally encoded penicillin-binding proteins (PBP), in particular PBP2
      encoded by the penA gene. The variety of penA alleles and resulting variant PBP2
      enzymes is described and the important amino acid substitutions are presented and
      discussed in a structural context.

PMID- 27690122
TI  - Effectiveness of a Lifestyle Intervention in Patients with Type 2 Diabetes: The
      Physical Activity and Nutrition for Diabetes in Alberta (PANDA) Trial.
AB  - Type 2 diabetes (T2D) patients often find integrating a new dietary pattern into
      their lifestyle challenging; therefore, the PANDA (Physical Activity and
      Nutrition for Diabetes in Alberta) menu plan intervention was developed to help
      people incorporate the Canadian Diabetes Association (CDA) nutrition therapy
      guidelines into their daily lives. The menu plan focused on recipes and foods
      that were accessible, available and acceptable to Albertans. The objective was to
      evaluate the effectiveness of the intervention on blood glucose control and
      dietary adherence and quality among patients with T2D. Participants with T2D (n =
      73) enrolled in a single-arm incorporating interactive education based on a four
      week menu plan that incorporated the recommendations of the CDA nutrition therapy
      guidelines. Post-intervention follow-up was conducted at three and six months.
      After three months, there were beneficial changes in A1c (-0.7%), body mass index
      (BMI, -0.6 kg/m2), diastolic blood pressure (-4 mmHg), total cholesterol (-63
      mg/dL), HDL- (+28 mg/dL) and LDL-cholesterol (-89 mg/dL), Healthy Eating Index
      (+2.1 score) and perceived dietary adherence (+8.5 score) (all p < 0.05). The
      significant improvements in A1c, BMI and lipids were maintained at six months.
      The PANDA menu plan intervention was effective in improving glycemic control and
      diet quality. The results suggest that a dietary intervention incorporating
      interactive education sessions focused on menu planning with familiar, accessible
      foods may be effective for diabetes management.

PMID- 27690123
TI  - The role of Polycomb in stem cell genome architecture.
AB  - Polycomb-group proteins maintain embryonic stem cell identity by repressing genes
      that encode for developmental regulatory factors. Failure to properly control
      developmental transcription programs by Polycomb proteins is linked to disease
      and embryonic lethality. Recent technological advances have revealed that
      developmentally repressed genes tend to cluster in the three-dimensional space of
      the nucleus. Importantly, spatial clustering of developmental genes is
      fundamental for the correct regulation of gene expression during early
      development. Here, we outline novel insights and perspectives regarding the
      function of Polycomb complexes in shaping the stem cell genome architecture, and
      discuss how this function might be required to properly orchestrate
      transcriptional programs during differentiation.

PMID- 27690124
TI  - Effects of acoustic periodicity, intelligibility, and pre-stimulus alpha power on
      the event-related potentials in response to speech.
AB  - Magneto- and electroencephalographic (M/EEG) signals in response to acoustically
      degraded speech have been examined by several recent studies. Unambiguously
      interpreting the results is complicated by the fact that speech signal
      manipulations affect acoustics and intelligibility alike. In the current EEG
      study, the acoustic properties of the stimuli were altered and the trials were
      sorted according to the correctness of the listeners' spoken responses to
      separate out these two factors. Firstly, more periodicity (i.e. voicing) rendered
      the event-related potentials (ERPs) more negative during the first second after
      sentence onset, indicating a greater cortical sensitivity to auditory input with
      a pitch. Secondly, we observed a larger contingent negative variation (CNV)
      during sentence presentation when the subjects could subsequently repeat more
      words correctly. Additionally, slow alpha power (7-10Hz) before sentences with
      the least correctly repeated words was increased, which may indicate that
      subjects have not been focussed on the upcoming task.

PMID- 27690125
TI  - Bilateral parietal contributions to spatial language.
AB  - It is commonly held that language is largely lateralized to the left hemisphere
      in most individuals, whereas spatial processing is associated with right
      hemisphere regions. In recent years, a number of neuroimaging studies have
      yielded conflicting results regarding the role of language and spatial processing
      areas in processing language about space (e.g., Carpenter, Just, Keller, Eddy, &
      Thulborn, 1999; Damasio et al., 2001). In the present study, we used sparse
      scanning event-related functional magnetic resonance imaging (fMRI) to
      investigate the neural correlates of spatial language, that is; language used to
      communicate the spatial relationship of one object to another. During scanning,
      participants listened to sentences about object relationships that were either
      spatial or non-spatial in nature (color or size relationships). Sentences
      describing spatial relationships elicited more activation in the superior
      parietal lobule and precuneus bilaterally in comparison to sentences describing
      size or color relationships. Activation of the precuneus suggests that spatial
      sentences elicit spatial-mental imagery, while the activation of the SPL suggests
      sentences containing spatial language involve integration of two distinct sets of
      information - linguistic and spatial.

PMID- 27690126
TI  - Urine Bacterial Community Convergence through Fertilizer Production: Storage,
      Pasteurization, and Struvite Precipitation.
AB  - Source-separated human urine was collected from six public events to study the
      impact of urine processing and storage on bacterial community composition and
      viability. Illumina 16S rRNA gene sequencing revealed a complex community of
      bacteria in fresh urine that differed across collection events. Despite the harsh
      chemical conditions of stored urine (pH > 9 and total ammonia nitrogen > 4000 mg
      N/L), bacteria consistently grew to 5 +/- 2 * 108 cells/mL. Storing hydrolyzed
      urine for any amount of time significantly reduced the number of operational
      taxonomic units (OTUs) to 130 +/- 70, increased Pielou evenness to 0.60 +/- 0.06,
      and produced communities dominated by Clostridiales and Lactobacillales. After 80
      days of storage, all six urine samples from different starting materials
      converged to these characteristics. Urine pasteurization or struvite
      precipitation did not change the microbial community, even when pasteurized urine
      was stored for an additional 70 days. Pasteurization decreased metabolic activity
      by 50 +/- 10% and additional storage after pasteurization did not lead to
      recovery of metabolic activity. Urine-derived fertilizers consistently contained
      16S rRNA genes belonging to Tissierella, Erysipelothrix, Atopostipes,
      Bacteroides, and many Clostridiales OTUs; additional experiments must determine
      whether pathogenic species are present, responsible for observed metabolic
      activity, or regrow when applied.

PMID- 27690127
TI  - Depletion of Neutrophils Promotes the Resolution of Pulmonary Inflammation and
      Fibrosis in Mice Infected with Paracoccidioides brasiliensis.
AB  - Chronic stages of paracoccidioidomycosis (PCM) are characterized by granulomatous
      lesions which promote the development of pulmonary fibrosis leading to the loss
      of respiratory function in 50% of patients; in addition, it has been observed
      that neutrophils predominate during these chronic stages of P. brasiliensis
      infection. The goal of this study was to evaluate the role of the neutrophil
      during the chronic stages of experimental pulmonary PCM and during the fibrosis
      development and tissue repair using a monoclonal specific to this phagocytic
      cell. Male BALB/c mice were inoculated intranasally with 1.5x106 P. brasiliensis
      yeast cells. A monoclonal antibody specific to neutrophils was administered at 4
      weeks post-inoculation followed by doses every 48h during two weeks. Mice were
      sacrificed at 8 and 12 weeks post-inoculation to assess cellularity, fungal load,
      cytokine/chemokine levels, histopathological analysis, collagen and expression of
      genes related to fibrosis development. Depletion of neutrophils was associated
      with a significant decrease in the number of eosinophils, dendritic cells, B
      cells, CD4-T cells, MDSCs and Treg cells, fungal load and levels of most of the
      pro-inflammatory cytokines/chemokines evaluated, including IL-17, TNF-alpha and
      TGF-beta1. Recovery of lung architecture was also associated with reduced levels
      of collagen, high expression of TGF-beta3, matrix metalloproteinase (MMP)-12 and 
      14, and decreased expression of tissue inhibitor metalloproteinase (TIMP)-2, and
      MMP-8. Depletion of neutrophils might attenuate lung fibrosis and inflammation
      through down-regulating TGF-beta1, TNF-alpha, IL-17, MMP-8 and TIMP-2. These
      results suggest that neutrophil could be considered as a therapeutic target in
      pulmonary fibrosis induced by P. brasiliensis.

PMID- 27690128
TI  - Characterization of a Thermoresponsive Chitosan Derivative as a Potential Draw
      Solute for Forward Osmosis.
AB  - A thermoresponsive chitosan derivative was synthesized by reacting chitosan (CS)
      with butyl glycidyl ether (BGE) to break the inter- and intramolecular hydrogen
      bonds of the polymer. An aqueous solution of the thermoresponsive CS derivative
      exhibits a lower critical solution temperature (LCST) than CS, and it undergoes a
      phase transition separation when the temperature changes. Successful
      incorporation of BGE into the CS was confirmed by FTIR and XPS analyses. Varying
      the BGE content and the concentration of the aqueous solution produced different
      LCST ranges, as shown by transmittance vs temperature curves. The particle size
      was observed by scanning electron microscopy, which revealed that the particles
      were smaller and well dispersed at 15  degrees C, whereas the particles became
      larger and tended to aggregate at 60  degrees C. A similar trend was observed
      with the mean particle size measured using dynamic light scattering. Positron
      annihilation lifetime spectroscopy data also revealed the reversibility of the
      particle properties as a function of temperature. Microstructure analysis showed
      that the particles had larger free-volume sizes at 15  degrees C than at 60 
      degrees C. The particles were also found to be nontoxic with 92% cell survival. A
      simple forward osmosis (FO) test for dye dehydration revealed the potential use
      of the thermoresponsive chitosan derivative as a draw solute with a flux of 8.6
      L/m2 h and rejection of 99.8%.

PMID- 27690130
TI  - Identification and Characterization of Two Human Monocyte-Derived Dendritic Cell
      Subpopulations with Different Functions in Dying Cell Clearance and Different
      Patterns of Cell Death.
AB  - Human monocyte-derived dendritic cells (mdDCs) are versatile cells that are used
      widely for research and experimental therapies. Although different culture
      conditions can affect their characteristics, there are no known subpopulations.
      Since monocytes differentiate into dendritic cells (DCs) in a variety of tissues
      and contexts, we asked whether they can give rise to different subpopulations. In
      this work we set out to characterize two human mdDC subpopulations that we
      identified and termed small (DC-S) and large (DC-L). Morphologically, DC-L are
      larger, more granular and have a more complex cell membrane. Phenotypically, DC-L
      show higher expression of a wide panel of surface molecules and stronger
      responses to maturation stimuli. Transcriptomic analysis confirmed their separate
      identities and findings were consistent with the phenotypes observed. Although
      they show similar apoptotic cell uptake, DC-L have different capabilities for
      phagocytosis, demonstrate better antigen processing, and have significantly
      better necrotic cell uptake. These subpopulations also have different patterns of
      cell death, with DC-L presenting an inflammatory, "dangerous" phenotype while DC
      S mostly downregulate their surface markers upon cell death. Apoptotic cells
      induce an immune-suppressed phenotype, which becomes more pronounced among DC-L,
      especially after the addition of lipopolysaccharide. We propose that these two
      subpopulations correspond to inflammatory (DC-L) and steady-state (DC-S) DC
      classes that have been previously described in mice and humans.

PMID- 27690129
TI  - Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired
      Growth in Children in Northeast Brazil.
AB  - Critical to the design and assessment of interventions for enteropathy and its
      developmental consequences in children living in impoverished conditions are non
      invasive biomarkers that can detect intestinal damage and predict its effects on
      growth and development. We therefore assessed fecal, urinary and systemic
      biomarkers of enteropathy and growth predictors in 375 6-26 month-old children
      with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil.
      301 of these children returned for followup anthropometry after 2-6m. Biomarkers
      that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin
      (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption);
      and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting
      impaired defenses). In contrast, subsequent growth was predicted in those with
      higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA
      (showing intestinal barrier disruption and inflammation). Better growth was
      predicted in girls with higher plasma citrulline and in boys with higher plasma
      tryptophan. Interactions were also seen with fecal MPO and neopterin in
      predicting subsequent growth impairment. Biomarkers clustered into markers of 1)
      functional intestinal barrier disruption and translocation, 2) structural
      intestinal barrier disruption and inflammation and 3) systemic inflammation.
      Principle components pathway analyses also showed that L/M with %L, I-FABP and
      MPO associate with impaired growth, while also (like MPO) associating with a
      systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic
      evidence of LPS translocation associated with stunting, while markers of barrier
      disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO
      and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier
      disruption, LPS translocation and of intestinal and systemic inflammation can
      help elucidate how we recognize, understand, and assess effective interventions
      for enteropathy and its growth and developmental consequences in children in
      impoverished settings.

PMID- 27690131
TI  - Outcome Reporting Bias in Government-Sponsored Policy Evaluations: A Qualitative
      Content Analysis of 13 Studies.
AB  - The reporting of evaluation outcomes can be a point of contention between
      evaluators and policy-makers when a given reform fails to fulfil its promises.
      Whereas evaluators are required to report outcomes in full, policy-makers have a
      vested interest in framing these outcomes in a positive light-especially when
      they previously expressed a commitment to the reform. The current evidence base
      is limited to a survey of policy evaluators, a study on reporting bias in
      education research and several studies investigating the influence of industry
      sponsorship on the reporting of clinical trials. The objective of this study was
      twofold. Firstly, it aimed to assess the risk of outcome reporting bias (ORB or
      'spin') in pilot evaluation reports, using seven indicators developed by
      clinicians. Secondly, it sought to examine how the government's commitment to a
      given reform may affect the level of ORB found in the corresponding evaluation
      report. To answer these questions, 13 evaluation reports were content-analysed,
      all of which found a non-significant effect of the intervention on its stated
      primary outcome. These reports were systematically selected from a dataset of 233
      pilot and experimental evaluations spanning three policy areas and 13 years of
      government-commissioned research in the UK. The results show that the risk of ORB
      is real. Indeed, all studies reviewed here resorted to at least one of the
      presentational strategies associated with a risk of spin. This study also found a
      small, negative association between the seniority of the reform's champion and
      the risk of ORB in the evaluation of that reform. The publication of protocols
      and the use of reporting guidelines are recommended.

PMID- 27690132
TI  - Deficits in metaphor but not in idiomatic processing are related to verbal
      hallucinations in patients with psychosis.
AB  - There is scant evidence that the verbal cognitive deficits observed in patients
      with psychosis are related to auditory verbal hallucinations. The understanding
      of metaphors and idiomatic expressions was investigated in a cohort of 90
      patients with active psychosis, and in 44 healthy controls. The Psychotic Symptom
      Rating Scales (PSYRATS: verbal hallucinations subscale) was used to measure the
      current verbal hallucinations episode; a subscore of the Launay-Slade
      Hallucination Scale was used to measure long-term propensity to auditory verbal
      hallucination-like experiences (HLEs) in the sample. The concurrent influence of
      education, IQ, and cognitive functioning in memory, attention, fluency, and
      processing speed on metaphor and idioms processing was investigated. Patients
      performed worse than healthy controls on all neuropsychological measures.
      Metaphor, but not idioms processing was poorer in patients with verbal
      hallucinations (n=46) when compared to patients without verbal hallucinations in
      the current episode (n=44). By taking into account confounding variables, the
      ability to produce explanations of metaphors was related to scores on the verbal
      HLEs in the whole sample of patients. Metaphor-comprehension deficit was related
      to the occurrence of auditory verbal hallucinations in patients with psychosis,
      suggesting that abnormal pragmatic inferential abilities have an impact on the
      mechanisms that cause hallucinatory experiences.

PMID- 27690133
TI  - Mediating and moderating effects of attentional control on the relationship
      between personality traits and attentional bias among Chinese medical students.
AB  - This study aimed to explore the mediating and moderating effects in the
      relationship between personality traits and attentional bias. A cross-sectional
      study was conducted among Chinese medical students. A total of 1047 Chinese
      medical students completed self-report measures of extraversion, neuroticism,
      attentional control, attention to positive information (API) and negative
      information (ANI). The data were analyzed with correlation, structural equation
      modeling, and multiple linear regression. The results revealed that attentional
      control mediated the effects of extraversion and neuroticism on attentional bias.
      Moreover, the association of neuroticism and ANI, and that of extraversion and
      API were both moderated by attentional control. These results extended our
      understanding of the relationship between extraversion, neuroticism, and
      attentional bias, by demonstrating that attentional control may serve as a
      protective factor for amplifying the positive emotional bias of extraverts and
      alleviating or eliminating the negative emotional bias of neurotics.

PMID- 27690134
TI  - Induced Obsessive Compulsive Symptoms (OCS) in schizophrenia patients under
      Atypical 2 Antipsychotics (AAPs): review and hypotheses.
AB  - The prevalence of OCS and OCD is higher in schizophrenic patients than in the
      general population. These disorders are sometimes induced by AAPs. There is
      higher frequency of OCS and greater severity in patients treated with
      antipsychotics with predominant anti-serotoninergic profiles opposed to those
      with predominant dopaminergic blockade. Induced OCS may be due to complex
      neuromodulation involving many serotonin, dopamine and glutamate receptors and
      several subtypes. Concerning connectivity, AAPs differentially influence the BOLD
      signal, depending on the intensity of D2 receptor blockade. The OFC could play a
      significant role, on account of its involvement in inhibitory control. There is a
      paradox: AAPs are efficient as augmentation to SSRI in treatment resistant OCD,
      some of them such as risperidone or aripiprazole have favourable effects in
      schizoptypic OCD, but AAPs cause induced OCS in schizophrenic patients. When
      prescribing AAPs, we should inform patients about this potential side effect and
      assess systematically OCS with Y-BOCS assessment after 1 month of treatment.
      Afterwards there are different strategies: Aripiprazole in combination can reduce
      OCS induced by clozapine, SSRI are slightly effective and CBT shows a few
      encouraging results. OCS are sometimes dose-dependent, so we also recommend
      prescribing the minimum effective dose and gradual introduction.

PMID- 27690135
TI  - Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and
      Enhanced Resistance to ER Stress in Caenorhabditis elegans.
AB  - The translation initiation factor eIF3 is a multi-subunit protein complex that
      coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior
      studies have demonstrated that not all subunits of eIF3 are essential for the
      initiation of translation, suggesting that some subunits may serve regulatory
      roles. Here, we show that loss-of-function mutations in the genes encoding the
      conserved eIF3k and eIF3l subunits of the translation initiation complex eIF3
      result in a 40% extension in lifespan and enhanced resistance to endoplasmic
      reticulum (ER) stress in Caenorhabditis elegans. In contrast to previously
      described mutations in genes encoding translation initiation components that
      confer lifespan extension in C. elegans, loss-of-function mutations in eif-3.K or
      eif-3.L are viable, and mutants show normal rates of growth and development, and
      have wild-type levels of bulk protein synthesis. Lifespan extension resulting
      from EIF-3.K or EIF-3.L deficiency is suppressed by a mutation in the Forkhead
      family transcription factor DAF-16. Mutations in eif-3.K or eif-3.L also confer
      enhanced resistance to ER stress, independent of IRE-1-XBP-1, ATF-6, and PEK-1,
      and independent of DAF-16. Our data suggest a pivotal functional role for
      conserved eIF3k and eIF3l accessory subunits of eIF3 in the regulation of
      cellular and organismal responses to ER stress and aging.

PMID- 27690137
TI  - A cut above the rest? Private anthropometrics in marriage markets.
AB  - A large body of economic research suggests that publicly observable
      anthropometric characteristics affect labor and marriage market outcomes. Private
      anthropometrics may not affect these outcomes. We examine male circumcision in
      marriage markets in Zambia. Our analysis reveals substantial variation across
      local marriage markets in circumcision prevalence relative to preference for
      circumcised partners, as well as excess aggregate demand for circumcised males.
      Regression estimates suggest a marriage market premium of approximately one-half
      to one year of additional schooling for matching with a partner of preferred
      anthropometric type in a local marriage market with excess demand for that
      anthropometric characteristic.

PMID- 27690136
TI  - Chrysin exerts neuroprotective effects against 3-Nitropropionic acid induced
      behavioral despair-Mitochondrial dysfunction and striatal apoptosis via
      upregulating Bcl-2 gene and downregulating Bax-Bad genes in male wistar rats.
AB  - 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of mitochondrial
      complex-II that causes transcriptional dysregulation, bioenergetics failure,
      protein aggregation and oxidative damage similar to Huntington's disease (HD)
      pathogenesis. Chrysin, a bioactive flavonoid reported to have anti-inflammation,
      antioxidant, vasorelaxant and neuroprotective property. The present study was
      framed to determine the neuroprotective efficiency of chrysin upon 3-NP induced
      oxidative stress, mitochondrial dysfunctions and neurodegeneration. 3-NP (10mg/kg
      b.w. i.p.) administration for 14days exhibited significant (P<0.01) behavioral
      alterations, mitochondrial dysfunction and oxidative damages to biomolecules,
      finally causes cell death. Chrysin at 50mg/kg b.w. orally for 14days improved all
      the behavioral performances and regulated the complex activities in mitochondria.
      Further, chrysin diminished the oxidative stress markers (lipid peroxidation,
      nitrite and protein carbonyls) by significantly (P<0.01) improving the
      antioxidant status (superoxide dismutase, catalase and reduced glutathione) in
      striatal mitochondria. Indeed, chrysin prevents apoptosis by upregulating the Bcl
      2 mRNA expression and downregulating the pro-apoptotic (Bax, Bad) mRNAs in 3-NP
      induced condition. Furthermore, the survival of striatal neurons against 3-NP
      toxicity was enhanced upon chrysin treatment which was evidenced by observing
      histopathological studies. Hence, the present study collectively suggests that
      the chrysin can serve as a potential therapeutic agent on 3-NP induced
      mitochondrial deficits and subsequent apoptosis.

PMID- 27690138
TI  - Discriminative Analysis of Migraine without Aura: Using Functional and Structural
      MRI with a Multi-Feature Classification Approach.
AB  - Magnetic resonance imaging (MRI) is by nature a multi-modality technique that
      provides complementary information about different aspects of diseases. So far no
      attempts have been reported to assess the potential of multi-modal MRI in
      discriminating individuals with and without migraine, so in this study, we
      proposed a classification approach to examine whether or not the integration of
      multiple MRI features could improve the classification performance between
      migraine patients without aura (MWoA) and healthy controls. Twenty-one MWoA
      patients and 28 healthy controls participated in this study. Resting-state
      functional MRI data was acquired to derive three functional measures: the
      amplitude of low-frequency fluctuations, regional homogeneity and regional
      functional correlation strength; and structural MRI data was obtained to measure
      the regional gray matter volume. For each measure, the values of 116 pre-defined
      regions of interest were extracted as classification features. Features were
      first selected and combined by a multi-kernel strategy; then a support vector
      machine classifier was trained to distinguish the subjects at individual level.
      The performance of the classifier was evaluated using a leave-one-out cross
      validation method, and the final classification accuracy obtained was 83.67%
      (with a sensitivity of 92.86% and a specificity of 71.43%). The anterior
      cingulate cortex, prefrontal cortex, orbitofrontal cortex and the insula
      contributed the most discriminative features. In general, our proposed framework
      shows a promising classification capability for MWoA by integrating information
      from multiple MRI features.

PMID- 27690139
TI  - Trends in cigarette use, by serious psychological distress status in the United
      States, 1998-2013.
AB  - OBJECTIVES: The study compared trends in current and heavy cigarette smoking
      between adults with and without serious psychological distress (SPD). METHODS:
      This study examined data from 480,024 adults aged 18years or older in the 1998
      2013 National Health Interview Survey (NHIS) public use files. SPD is defined as
      having a Kessler-6 score of 13 or higher in the past month. Trends in the
      prevalence of current smoking and heavy smoking for 2-year time periods were
      assessed among those with versus those without SPD using logistic regression;
      tests of interaction terms determined whether smoking trends differed by SPD
      status. RESULTS: The prevalence of current smoking decreased over time among
      adults without SPD (adjusted odds ratio [AOR]=0.97, 95% CI=0.97-0.98), but
      remained stable among adults with SPD (AOR=1.01, 95% CI=0.99-1.03). Both groups
      had significant declines in heavy smoking over time; however, the rates of
      decline were greater among adults without versus with SPD (AOR=0.87, 95% CI=0.86
      0.88 and AOR=0.91, 95% CI=0.88-0.94, respectively). CONCLUSIONS: The prevalence
      of current smoking is not declining among adults with SPD, and the prevalence of
      heavy smoking is not declining as quickly among adults with SPD as compared with
      those without SPD. Smoking cessation efforts may need to target these populations
      and tailor programs accordingly.

PMID- 27690140
TI  - Performance of a real-time PCR-based approach and droplet digital PCR in
      detecting human parechovirus type 3 RNA.
AB  - BACKGROUND: Human parechovirus type 3 (HPeV3) is an emerging virus that causes
      sepsis and meningoencephalitis in neonates and young infants. Correct diagnosis
      of HPeV3 infection is critical in determining appropriate management and
      predicting patients' clinical course. Real-time reverse transcription PCR (RT
      PCR) analysis of serum and/or cerebrospinal fluid (CSF) has been used to diagnose
      HPeV3 infection; however, the assay detection limits have not been fully
      evaluated. OBJECTIVES: We tested the hypothesis that droplet digital RT-PCR (RT
      ddPCR)-a novel technique that precisely quantitates low-copy target genes by
      diluting and partitioning samples into compartments-increases the detection rate
      of HPeV3 RNA as compared with real-time RT-PCR. STUDY DESIGN: Using samples with
      predetermined HPeV3 copy numbers, we evaluated one-step and two-step RT-ddPCR.
      Then, we tested two-step RT-ddPCR and real-time RT-PCR, using clinical samples
      with low copy numbers. Finally, we used two-step RT-ddPCR to evaluate clinical
      samples obtained from HPeV3-infected patients with positive serum but negative
      CSF, as determined by real-time RT-PCR. RESULTS: Two-step RT-ddPCR was less
      variable and more specific than one-step RT-ddPCR. Two-step RT-ddPCR detected
      HPeV3 RNA in all six CSF samples; four samples (67%) were reproducibly positive
      and the other two samples (33%) were positive at least once in four replicates.
      Finally, no nonspecific droplet was positive by two-step RT-ddPCR. CONCLUSIONS:
      Two-step RT-ddPCR may enhance the rate of HPeV3 RNA detection from samples with
      low viral loads, thereby improving diagnosis and management of HPeV3-infected
      patients.

PMID- 27690142
TI  - Visible-Light Photoredox Borylation of Aryl Halides and Subsequent Aerobic
      Oxidative Hydroxylation.
AB  - Efficient and practical visible-light photoredox borylation of aryl halides and
      subsequent aerobic oxidative hydroxylation were developed. The protocols use
      readily available aryl halides and bis(pinacolato)diboron as the starting
      materials, fac-Ir(ppy)3 as the photocatalyst, and corresponding arylboronic
      esters and phenols were obtained in good yields. The methods show some advantages
      including simple equipment, mild conditions, easy operation, and wide substrate
      scope. Therefore, they should provide a valuable strategy for chemical
      transformations.

PMID- 27690143
TI  - Bioinspired Design of Polycaprolactone Composite Nanofibers as Artificial Bone
      Extracellular Matrix for Bone Regeneration Application.
AB  - The design and development of functional biomimetic systems for programmed stem
      cell response is a field of topical interest. To mimic bone extracellular matrix,
      we present an innovative strategy for constructing drug-loaded composite
      nanofibrous scaffolds in this study, which could integrate multiple cues from
      calcium phosphate mineral, bioactive molecule, and highly ordered fiber
      topography for the control of stem cell fate. Briefly, inspired by mussel
      adhesion mechanism, a polydopamine (pDA)-templated nanohydroxyapatite (tHA) was
      synthesized and then surface-functionalized with bone morphogenetic protein-7
      derived peptides via catechol chemistry. Afterward, the resulting peptide-loaded
      tHA (tHA/pep) particles were blended with polycaprolactone (PCL) solution to
      fabricate electrospun hybrid nanofibers with random and aligned orientation. Our
      research demonstrated that the bioactivity of grafted peptides was retained in
      composite nanofibers. Compared to controls, PCL-tHA/pep composite nanofibers
      showed improved cytocompatibility. Moreover, the incorporated tHA/pep particles
      in nanofibers could further facilitate osteogenic differentiation potential of
      human mesenchymal stem cells (hMSCs). More importantly, the aligned PCL-tHA/pep
      composite nanofibers showed more osteogenic activity than did randomly oriented
      counterparts, even under nonosteoinductive conditions, indicating excellent
      performance of biomimetic design in cell fate decision. After in vivo
      implantation, the PCL-tHA/pep composite nanofibers with highly ordered structure
      could significantly promote the regeneration of lamellar-like bones in a rat
      calvarial critical-sized defect. Accordingly, the presented strategy in our work
      could be applied for a wide range of potential applications in not only bone
      regeneration application but also pharmaceutical science.

PMID- 27690141
TI  - Genetic characterization of influenza viruses from influenza-related hospital
      admissions in the St. Petersburg and Valencia sites of the Global Influenza
      Hospital Surveillance Network during the 2013/14 influenza season.
AB  - BACKGROUND: Continuous surveillance for genetic changes in circulating influenza
      viruses is needed to guide influenza prevention and control. OBJECTIVES: To
      compare intra-seasonal influenza genetic diversity of hemagglutinin in influenza
      A strains isolated from influenza hospital admissions collected at two distinct
      sites during the same season. STUDY DESIGN: Comparative phylogenetic analysis of
      full-length hemagglutinin genes from 77 isolated influenza A viruses from the St.
      Petersburg, Russian Federation and Valencia, Spain sites of the Global Influenza
      Hospital Surveillance Network (GIHSN) during the 2013/14 season. RESULTS: We
      found significant variability in A(H3N2) and A(H1N1)pdm09 viruses between the two
      sites, with nucleotide variation at antigenic positions much lower for
      A(H1N1)pdm09 than for A(H3N2) viruses. For A(H1N1)pdm09, antigenic sites differed
      by three to four amino acids from the vaccine strain, two of them common to all
      tested isolates. For A(H3N2) viruses, antigenic sites differed by six to nine
      amino acids from the vaccine strain, four of them common to all tested isolates.
      A fifth amino acid substitution in the antigenic sites of A(H3N2) defined a new
      clade, 3C.2. For both influenza A subtypes, pairwise amino acid distances between
      circulating viruses and vaccine strains were significantly higher at antigenic
      than at non-antigenic sites. Whereas A(H1N1)pdm09 viruses clustered with clade 6B
      and 94% of A(H3N2) with clade 3C.3, at both study sites A(H3N2) clade 3C.2
      viruses emerged towards the end of the season, showing greater pairwise amino
      acid distances from the vaccine strain compared to the predominant clade 3C.3.
      CONCLUSIONS: Influenza A antigenic variants differed between St. Petersburg and
      Valencia, and A(H3N2) clade 3C.2 viruses were characterized by more amino acid
      differences from the vaccine strain, especially at the antigenic sites.

PMID- 27690144
TI  - Sequential oxygen chemisorption on Fe13 clusters: from first-principles to
      practical insights.
AB  - With the advent of more precise technologies allowing manipulation of matter at
      nanoscopic scales and novel characterization techniques, a growing field of
      research is focused on magnetic materials of technical interest-such as Fe
      clusters-and their related physical-chemical processes. In this study, we present
      the results of the sequential oxidation process of the Fe13 cluster by
      considering the physical-chemistry properties of the ground state configurations
      of Fe13O n ([Formula: see text]) clusters. We develop an exhaustive ab initio
      study into the GGA approach and explore the effect of the chemisorption of oxygen
      on the structural properties, the chemical stability, the magnetization and the
      magnetic anisotropy energy (MAE) of the systems. Our results clearly indicate
      that: (i) one of the studied clusters, Fe13O17, presents the biggest
      electrophilicity index and the lowest chemical hardness, being the most reactive
      among the systems studied; (ii) the Fe13O10 exhibits a much more enhanced
      magnetization than other related clusters intended for health and technology
      applications (Sun et al 2007 J. Phys. Chem. C 111 4159-63), so that it might be a
      better candidate for those purposes; and (iii) the MAE presents a complex and
      intriguing landscape that encourages thinking about the plausible control of
      magnetic states focused on technical applications.

PMID- 27690145
TI  - Role of Surface Perfection in Chemical Force Microscopy.
AB  - In this paper we investigate the effect that the quality of the gold substrate
      has upon the distribution of adhesion force measurements in chemical force
      microscopy. Gold samples have been prepared by two protocols which give either
      predominantly single-crystal Au(111) or polycrystalline gold films on mica. Gold
      coated tips and surfaces were functionalized with self-assembled monolayers
      terminating in carboxylic groups, and more that 500 force-distance plots were
      taken. Analysis of these plots revealed a 50% narrower distribution of adhesion
      forces between monolayers prepared on single-crystal surfaces and monolayers
      prepared on polycrystalline gold, when measurements were repeated at a single
      point. However when measurements were taken over a 1-MUm2 area, the distribution
      of adhesion forces was similar for both samples. An explanation for this may lie
      in the size of the domains on the gold surface relative to the contact area of
      the tip.

PMID- 27690146
TI  - LnBSb2O8 (Ln = Sm, Eu, Gd, Tb): A Series of Lanthanide Boroantimonates with
      Unusual 3D Anionic Structures.
AB  - A series of lanthanide boroantimonates, namely, LnBSb2O8 (Ln = Sm 1, Eu 2, Gd 3,
      and Tb 4) have been successfully synthesized by high temperature solid-state
      reactions for the first time. They are isostructural and feature novel three
      dimensional (3D) frameworks composed of 2D [Sb3O12]9- layers interconnected by 1D
      [SbBO7]6- chains with remaining BO3 groups hanging on the walls of the 1D 6
      membered-ring (MR) tunnels along the a-axis, and the lanthanide ions filled in
      the voids of the anionic structure. They exhibit high thermal stability (up to
      900  degrees C). Luminescent studies suggest that compounds 1, 2, and 4 have
      potential application as orange, red, and green light luminescent materials,
      respectively. Magnetic measurements reveal ferromagnetic coupling interactions in
      compound 3 and antiferromagnetic coupling interactions between magnetic centers
      in compounds 1, 2, and 4.

PMID- 27690147
TI  - Phthalate exposure, flavonoid consumption and breast cancer risk among Mexican
      women.
AB  - OBJECTIVE: To evaluate if selected phthalate exposure and flavonoid intake
      interact on breast cancer (BC) risk. MATERIAL AND METHODS: Interviews and urine
      samples were obtained from 233 women with histologically confirmed BC and 221
      healthy controls matched by age and place of residence, from various states of
      northern Mexico. Urinary metabolites concentrations of diethyl phthalate (DEP),
      butyl benzyl phthalate (BBzP) and dioctyl phthalate (DOP) were determined by
      solid-phase extraction coupled with high-performance liquid
      chromatography/isotope dilution/tandem mass spectrometry. Using a
      semiquantitative food frequency questionnaire, consumption of five types of
      flavonoids (anthocyanidins, flavan-3-ols, flavanones, flavones and flavonols) was
      estimated according to three food groups: vegetables, fruits and legumes-oil
      seeds. RESULTS: A higher intake of anthocyanidins and flavan-3-ols (from
      vegetables), synergistically increased the negative association between BBzP and
      BC. No other significant flavonoid-phthalate multiplicative interactions on the
      risk for BC were found. CONCLUSION: The consumption of some flavonoids may
      interact with exposure to phthalates on the risk of BC. Epidemiological and
      underlying mechanisms information is still insufficient and requires further
      investigations.

PMID- 27690149
TI  - Chemoenzymatic Total Synthesis of Hydromorphone by an Oxidative
      Dearomatization/Intramolecular [4 + 2] Cycloaddition Sequence: A Second
      Generation Approach.
AB  - A second-generation approach to the synthesis of hydromorphone by oxidative
      dearomatization/Diels-Alder cycloaddition was investigated. Detailed analysis of
      the stereochemical outcome of the [4 + 2] cycloaddition was performed first on a
      truncated model system as well as on the material leading to ent-hydromorphone.
      The stereochemical assignments were made by NMR and X-ray methods. The second
      generation synthesis of hydromorphone was completed in both enantiomeric series.
      Improvements in the dearomatization conditions were attained using hypervalent
      iodine reagents instead of Pb(OAc)4. Electrochemical methods of oxidative
      dearomatization were also investigated. New conditions enabling the
      rearomatization of ring A from the methoxyketal were developed, and a formal
      synthesis of the natural enantiomer of hydromorphone was completed. Experimental
      and spectral data are provided for all new compounds.

PMID- 27690148
TI  - In search of the severity dimension of traffic events: Extended Delta-V as a
      traffic conflict indicator.
AB  - Most existing traffic conflict indicators do not sufficiently take into account
      the severity of the injuries resulting from a collision had it occurred. Thus
      far, most of the indicators that have been developed express the severity of a
      traffic encounter as their proximity to a collision in terms of time or space.
      This paper presents the theoretical framework and the first implementation of
      Extended Delta-V as a measure of traffic conflict severity in site-based
      observations. It is derived from the concept of Delta-V as it is applied in crash
      reconstructions, which refers to the change of velocity experienced by a road
      user during a crash. The concept of Delta-V is recognised as an important
      predictor of crash outcome severity. The paper explains how the measure is
      operationalised within the context of traffic conflict observations. The Extended
      Delta-V traffic conflict measure integrates the proximity to a crash as well as
      the outcome severity in the event a crash would have taken place, which are both
      important dimensions in defining the severity of a traffic event. The results
      from a case study are presented in which a number of traffic conflict indicators
      are calculated for interactions between left turning vehicles and vehicles
      driving straight through a signalised intersection. The results suggest that the
      Extended Delta-V indicator seems to perform well at selecting the most severe
      traffic events. The paper discusses how the indicator overcomes a number of
      limitations of traditional measures of conflict severity. While this is a
      promising first step towards operationalising an improved measure of traffic
      conflict severity, additional research is needed to further develop and validate
      the indicator.

PMID- 27690150
TI  - Correction of C(O)F2 Yields in "Atmospheric Chemistry of (CF3)2CHOCH3,
      (CF3)2CHOCHO, and CF3C(O)OCH3".

PMID- 27690151
TI  - Red Meat and Colorectal Cancer: Exploring the Potential HCA Connection.

PMID- 27690152
TI  - Molecular Study of Deletional and Nondeletional Mutations on the alpha-Globin
      Locus in the Azeri Population of Northwestern Iran.
AB  - The aim of this study was to determine the molecular spectrum and frequency of
      deletional and nondeletional alpha-thalassemia (alpha-thal) mutations and the
      genotype-phenotype correlation in common mutations in the Azeri population of
      Northwestern Iran. A total of 1256 potential carriers with microcytic and
      hypochromic anemia and normal Hb A2 levels (<3.5%) and without iron deficiency
      anemia plus three fetuses were identified. Multiplex gap-polymerase chain
      reaction (gap-PCR) and sequencing for alpha-thal mutations were carried out. In
      606 individuals, the alpha-globin gene was normal, but in 650 persons (51.6%) and
      three fetuses, 10 different mutations were detected. The most frequent deletional
      genotypes were as follows: alphaalpha/-alpha3.7 (61.7%), -alpha3.7/-alpha3.7
      (11.9%), alphaalpha/-alpha4.2 (4.6%), alphaalpha/- -MED (4.3%) and alphaalpha/
      (alpha)20.5 (3.8%). The most frequent nondeletional genotypes were
      alphaalpha/alphaIVS-I (-5 nt)alpha (HBA2: c.95+2_95+6delTGAGG) and
      alphaalpha/alphaPoly A2alpha [polyadenylation signal (polyA2) (AATAAA>AATGAA);
      HBA2: c.*96G>A] with frequencies of 1.08% and 0.92%, respectively. Meanwhile,
      7.71% of individuals with a proven beta-thalassemia (beta-thal) mutation were
      found to also carry an alpha-thal mutation. Persons having two functional alpha
      globin genes showed lower mean corpuscular volume (MCV) and mean corpuscular
      hemoglobin (Hb) (MCH) values compared to those with one mutated alpha-globin
      gene, provided that they had normal beta-globin genes. Overall, the incidence of
      alpha-thal was 2.7% in the Azeri population in Northwestern Iran. Our results
      showed that the variability of alpha-thal mutations are high in the Azeri
      population and that alpha-thal mutations are highly heterogeneous in both
      deletional and nondeletional genotype aspects.

PMID- 27690154
TI  - Secretome derived from breast tumor cell lines alters the morphology of human
      umbilical vein endothelial cells.
AB  - Metastases, responsible for most of the solid tumor associated deaths, require
      angiogenesis and changes in endothelial cells. In this work, the effect of the
      secretomes of three breast tumor cell lines (MCF-7, MDA-MB-231 and ZR-75-30) on
      human umbilical vein endothelial cells (HUVEC) morphology was investigated. HUVEC
      treated with secretomes from breast cells were analyzed by confocal and time
      lapse microscopy. Secretomes from ZR-75-30 and MDA-MB-231 cells modify the
      morphology and adhesion of HUVEC. These changes may provoke the loss of
      endothelial monolayer integrity. In consequence, tumor cells could have an
      increased access to circulation, which would then enhance metastasis.

PMID- 27690153
TI  - Strategies for improving drug delivery: nanocarriers and microenvironmental
      priming.
AB  - INTRODUCTION: The ultimate goal in the field of drug delivery is to exclusively
      direct therapeutic agents to pathological tissues in order to increase
      therapeutic efficacy and eliminate side effects. This goal is challenging due to
      multiple transport obstacles in the body. Strategies that improve drug transport
      exploit differences in the characteristics of normal and pathological tissues.
      Within the field of oncology, these concepts have laid the groundwork for a new
      discipline termed transport oncophysics. Areas covered: Efforts to improve drug
      biodistribution have mainly focused on nanocarriers that enable preferential
      accumulation of drugs in diseased tissues. A less common approach to enhance drug
      transport involves priming strategies that modulate the biological environment in
      ways that favor localized drug delivery. This review discusses a variety of
      priming and nanoparticle design strategies that have been used for drug delivery.
      Expert opinion: Combinations of priming agents and nanocarriers are likely to
      yield optimal drug distribution profiles. Although priming strategies have yet to
      be widely implemented, they represent promising solutions for overcoming
      biological transport barriers. In fact, such strategies are not restricted to
      priming the tumor microenvironment but can also be directed toward healthy tissue
      in order to reduce nanoparticle uptake.

PMID- 27690155
TI  - Cyclosporin a induces renal episodic hypoxia.
AB  - AIM: Cyclosporin A (CsA) causes renal toxicity. The underlying mechanisms are
      incompletely understood, but may involve renal hypoxia and hypoxia-inducible
      factors (Hifs). We sought for hypoxia and Hif in mouse kidneys with CsA-induced
      toxicity, assessed their time course, Hif-mediated responses and the impact of
      interventional Hif upregulation. METHODS: Mice received CsA or its solvent
      cremophore for up to 6 weeks. Low salt diet (Na+ ?) was given in combination with
      CsA to enhance toxicity. We assessed fine morphology, renal function, blood
      oxygen level-dependent magnetic resonance imaging under room air and following
      changes in breathing gas composition which correlate with vascular reactivity,
      pimonidazole adducts (which indicate O2 tensions below 10 mmHg), Hif-alpha
      proteins, as well as expression of Hif target genes. Stable Hif upregulation was
      achieved by inducible, Pax8-rtTA-based knockout of von Hippel-Lindau protein (Vhl
      KO), which is crucial for Hif-alpha degradation. RESULTS: Cyclosporin A
      transiently increased renal deoxyhaemoglobin (R2*). Augmented vascular reactivity
      was observed at 2 h, but decreased at 24 h after CsA treatment. Na+ ?/CsA
      provoked chronic renal failure with tubular degeneration and interstitial
      fibrosis. Nephron segments at risk for injury accumulated pimonidazole adducts,
      as well as Hif-alpha proteins. Remarkably, Hif target gene expression remained
      unchanged, while factor-inhibiting Hif (Fih) was enhanced. Na+ ?/CsA/Vhl-KO
      aggravated morpho-functional outcome of chronic renal CsA toxicity. CONCLUSIONS:
      Cyclosporin A provokes episodic hypoxia in nephron segments most susceptible to
      chronic CsA toxicity. Fih is upregulated and likely blocks further Hif activity.
      Continuous tubular Hif upregulation via Vhl-KO worsens the outcome of chronic CsA
      induced renal toxicity.

PMID- 27690156
TI  - Chemical exchange saturation transfer for predicting response to stereotactic
      radiosurgery in human brain metastasis.
AB  - PURPOSE: The purpose of this work was to determine the predictive value of
      chemical exchange saturation transfer (CEST) metrics in brain metastases treated
      with stereotactic radiosurgery (SRS). METHODS: CEST spectra at a radiofrequency
      power of 0.52 uT were collected on a 3 Tesla (T) magnetic resonance imaging from
      25 patients at three time points: pretreatment, 1 week, and 1 month post
      treatment. Amide proton transfer-weighted images and maps of the amplitude and
      width of Lorentzian-shaped CEST peaks and the relaxation-compensated AREX metric
      were constructed at the offset frequencies of amide, amine, and relayed nuclear
      Overhauser effect (NOE) from aliphatic groups as well as the broad magnetization
      transfer effect. Pretreatment CEST metrics, as well as CEST metric changes at 1
      week post-treatment, were compared to changes in tumor volume at 1 month.
      RESULTS: Significant (P < 0.05) 1-week predictive metrics included NOE peak
      amplitude (R = 0.69) in normal-appearing white matter (NAWM) and width (R = 
      0.55) in tumor. Baseline NOE in contralateral NAWM was negatively correlated (R =
      -0.69) with volume changes at 1 month. Metrics-defined outside tumor margins had
      higher correlation with volume changes than tumor regions of interest.
      CONCLUSION: CEST metrics, in particular, the NOE peak amplitude, can predict
      volume changes 1 month post-SRS. Magn Reson Med 78:1110-1120, 2017. (c) 2016
      International Society for Magnetic Resonance in Medicine.

PMID- 27690157
TI  - Testing the role of Michelson contrast for the perception of surface lightness.
AB  - It is still an unresolved question how the visual system perceives surface
      lightness given the ambiguity of the sensory input signal. We studied lightness
      perception using two-dimensional images of variegated checkerboards shown as
      perspective projections of three-dimensional objects. We manipulated the contrast
      of a target check relative to its surround either by rendering the image under
      different viewing conditions or by introducing noncoincidental changes of the
      reflectance of the surfaces adjacent to the target. We examined the predictive
      power of the normalized contrast model (Zeiner & Maertens, 2014) for the
      different viewing conditions (plain view vs. dark and light transparency) as well
      as for the noncoincidental surround changes (only high or only low reflectances
      in the surround). The model accounted for lightness matches across different
      viewing conditions but not for the surround changes. The observed simultaneous
      contrast effects were smaller than what would be predicted by the model. We
      evaluated two model extensions that-both relying on contrast-predicted the
      observed data well. Both model extensions point to the importance of contrast
      statistics across space and/or time for the computation of lightness, but it
      awaits future testing to evaluate whether and how the visual system could
      represent such statistics.

PMID- 27690158
TI  - Clarifying signal detection theoretic interpretations of the Muller-Lyer and
      sound-induced flash illusions.
AB  - In a recent article, Witt, Taylor, Sugovic, and Wixted (2015) made several claims
      about the way the Muller-Lyer and sound-induced flash illusions should influence
      the signal detection theory criterion and sensitivity measures, c and d'. Here,
      we address some crucial conceptual inconsistencies in their simulation of the
      Muller-Lyer illusion and clarify a previous analysis of the sound-induced flash
      illusion from the literature that is misinterpreted in their discussion.
      Alternative signal detection theoretic interpretations of both illusions are
      offered.

PMID- 27690159
TI  - Further clarifying signal detection theoretic interpretations of the Muller-Lyer
      and sound-induced flash illusions.

PMID- 27690160
TI  - The perceived depth from disparity as function of luminance contrast.
AB  - Does human vision show the contrast invariance expected of an ideal stereoscopic
      system for computing depth from disparity? We used random-dot stereograms to
      investigate the luminance contrast effect on perceived depth from disparity. The
      perceived depth of disparity corrugations was measured by adjusting the length of
      a horizontal line to match the perceived depth of the corrugations at various
      luminance contrasts. At each contrast, the perceived depth increased with
      disparity up to a critical value, decreasing with further increases in disparity.
      Both the maximum perceived depth and the disparity modulation level where this
      maximum occurred changed as a sigmoid function of luminance contrast. These
      results show that perceived depth from disparity depends in a complex manner on
      the luminance contrast in the image, providing significant limitations on depth
      perception at low contrasts in a lawful manner but that are incompatible with
      existing models of cortical disparity processing.

PMID- 27690161
TI  - Corrections.

PMID- 27690162
TI  - Corrections.

PMID- 27690164
TI  - Corrections.

PMID- 27690163
TI  - Temporal synchrony is an effective cue for grouping and segmentation in the
      absence of form cues.
AB  - The synchronous change of a feature across multiple discrete elements, i.e.,
      temporal synchrony, has been shown to be a powerful cue for grouping and
      segmentation. This has been demonstrated with both static and dynamic stimuli for
      a range of tasks. However, in addition to temporal synchrony, stimuli in previous
      research have included other cues which can also facilitate grouping and
      segmentation, such as good continuation and coherent spatial configuration. To
      evaluate the effectiveness of temporal synchrony for grouping and segmentation in
      isolation, here we measure signal detection thresholds using a global-Gabor
      stimulus in the presence/absence of a synchronous event. We also examine the
      impact of the spatial proximity of the to-be-grouped elements on the
      effectiveness of temporal synchrony, and the duration for which elements are
      bound together following a synchronous event in the absence of further
      segmentation cues. The results show that temporal synchrony (in isolation) is an
      effective cue for grouping local elements together to extract a global signal.
      Further, we find that the effectiveness of temporal synchrony as a cue for
      segmentation is modulated by the spatial proximity of signal elements. Finally,
      we demonstrate that following a synchronous event, elements are perceptually
      bound together for an average duration of 200 ms.

PMID- 27690165
TI  - What crowds in crowding?

PMID- 27690166
TI  - Visual input that matches the content of visual working memory requires less (not
      faster) evidence sampling to reach conscious access.
AB  - The content of visual working memory (VWM) affects the processing of concurrent
      visual input. Recently, it has been demonstrated that stimuli are released from
      interocular suppression faster when they match rather than mismatch a color that
      is memorized for subsequent recall. In order to investigate the nature of the
      interaction between visual representations elicited by VWM and visual
      representations elicited by retinal input, we modeled the perceptual processes
      leading up to this difference in suppression durations. We replicated the VWM
      modulation of suppression durations, and fitted sequential sampling models
      (linear ballistic accumulators) to the response time data. Model comparisons
      revealed that the data was best explained by a decrease in threshold for visual
      input that matches the content of VWM. Converging evidence was obtained by
      fitting similar sequential sampling models (shifted Wald model) to published
      datasets. Finally, to confirm that the previously observed threshold difference
      reflected processes occurring before rather than after the stimuli were released
      from suppression, we applied the same procedure to the data of an experiment in
      which stimuli were not interocularly suppressed. Here, we found no decrease in
      threshold for stimuli that match the content of VWM. We discuss our findings in
      light of a preactivation hypothesis, proposing that matching visual input taps
      into the same neural substrate that is already activated by a representation
      concurrently maintained in VWM, thereby reducing its threshold for reaching
      visual awareness.

PMID- 27690167
TI  - Age-dependent distractor suppression across the vision and motor domain.
AB  - The ability to inhibit distracting information-distractor suppression-is a
      fundamental process for the visual and motor systems. Whereas aging is typically
      linked to a general decline in cognitive processing, a specific impairment in
      distractor suppression is found during visual attention tasks. Despite this, the
      effect of aging on a human's capacity to inhibit distracting information during a
      motor task is currently unknown. Therefore, we tested the ability of young and
      older adults to inhibit distracting information during a visual attention (global
      local) and a motor (reaching) task. When faced with distractors, younger and
      older adults displayed significant behavioral impairments (accuracy and speed)
      across both tasks. However, these deficits were substantially enhanced in older
      adults. Intriguingly, the amount of distractor impairment observed within each
      participant was correlated across the visual and motor tasks, irrespective of age
      group. Thus, while all participants' ability to inhibit distractors was
      correlated across the visual and motor domain, older adults displayed a
      generalized distractor inhibition deficit. We propose that a shift from proactive
      to reactive control in older adults could explain such impairment. These results
      may have important implications regarding the ability of older adults to
      effectively deal with distractors during complex visuomotor tasks such as
      driving.

PMID- 27690168
TI  - Differential effects of visual uncertainty and contextual guidance on perceptual
      decisions: Evidence from eye and mouse tracking in visual search.
AB  - Visual search can be seen as a decision-making process that aims to assess
      whether a target is present or absent from a scene. In this perspective, eye
      movements collect evidence related to target detection and verification to guide
      the decision. We investigated whether, in real-world scenes, target detection and
      verification are differentially recruited in the decision-making process in the
      presence of prior information (expectations about target location) and perceptual
      uncertainty (noise). We used a mouse-tracking methodology with which mouse
      trajectories unveil components of decision-making and eye-tracking measures
      reflect target detection and verification. Indoor scenes were presented,
      including a target in usual or unusual locations or no target, and were degraded
      with additive noise (or no noise). Participants had to respond to the target's
      presence or absence. Degrading the scene delayed the decision due to increased
      verification times and reduced mouse velocity. Targets in unusual locations
      delayed the decision and deviated mouse trajectories toward the target-absent
      response. Detection times played a major role in these effects. Thus, target
      detection and verification processes influence decision-making by integrating the
      available sources of information differently and lead to an accumulation of
      evidence toward both the presence of a target and its absence.

PMID- 27690169
TI  - Luminance and chromatic signals interact differently with melanopsin activation
      to control the pupil light response.
AB  - Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the
      photopigment melanopsin. These cells receive afferent inputs from rods and cones,
      which provide inputs to the postreceptoral visual pathways. It is unknown,
      however, how melanopsin activation is integrated with postreceptoral signals to
      control the pupillary light reflex. This study reports human flicker pupillary
      responses measured using stimuli generated with a five-primary photostimulator
      that selectively modulated melanopsin, rod, S-, M-, and L-cone excitations in
      isolation, or in combination to produce postreceptoral signals. We first analyzed
      the light adaptation behavior of melanopsin activation and rod and cones signals.
      Second, we determined how melanopsin is integrated with postreceptoral signals by
      testing with cone luminance, chromatic blue-yellow, and chromatic red-green
      stimuli that were processed by magnocellular (MC), koniocellular (KC), and
      parvocellular (PC) pathways, respectively. A combined rod and melanopsin response
      was also measured. The relative phase of the postreceptoral signals was varied
      with respect to the melanopsin phase. The results showed that light adaptation
      behavior for all conditions was weaker than typical Weber adaptation. Melanopsin
      activation combined linearly with luminance, S-cone, and rod inputs, suggesting
      the locus of integration with MC and KC signals was retinal. The melanopsin
      contribution to phasic pupil responses was lower than luminance contributions,
      but much higher than S-cone contributions. Chromatic red-green modulation
      interacted with melanopsin activation nonlinearly as described by a "winner-takes
      all" process, suggesting the integration with PC signals might be mediated by a
      postretinal site.

PMID- 27690171
TI  - The flash-lag effect and the flash-drag effect in the same display.
AB  - Visual motion distorts the perceived position of a stimulus. In the flash-drag
      effect (FDE), the perceived position of a flash appears to be shifted in the
      direction of nearby motion. In the flash-lag effect (FLE), a flash adjacent to a
      moving stimulus appears to lag behind. The FLE has been explained by several
      models, including the differential latency hypothesis, that a moving stimulus has
      a shorter processing latency than a flash does. The FDE even occurs when the
      flash is presented earlier than the moving stimulus, and it has been discussed
      whether this temporal property can be explained by the differential latency
      model. In the present study, we simultaneously quantified the FDE and FLE using
      the random jump technique (Murakami, 2001b) and compared their temporal
      properties. While the positional offset between a randomly jumping stimulus and a
      flashed stimulus determined the FLE, a drifting grating appeared next to the
      flash at various stimulus-onset asynchronies to induce the FDE. The grating
      presented up to 200 ms after the flash onset induced the FDE, whose temporal
      tuning was explained by a simple convolution model incorporating stochastic
      fluctuations of differential latency estimated from the FLE data and a transient
      sustained temporal profile of motion signals. Thus, a common temporal mechanism
      to compute the stimulus position in reference to surrounding stimuli governs both
      the FDE and the FLE.

PMID- 27690170
TI  - The crowding factor method applied to parafoveal vision.
AB  - Crowding increases with eccentricity and is most readily observed in the
      periphery. During natural, active vision, however, central vision plays an
      important role. Measures of critical distance to estimate crowding are difficult
      in central vision, as these distances are small. Any overlap of flankers with the
      target may create an overlay masking confound. The crowding factor method avoids
      this issue by simultaneously modulating target size and flanker distance and
      using a ratio to compare crowded to uncrowded conditions. This method was
      developed and applied in the periphery (Petrov & Meleshkevich, 2011b). In this
      work, we apply the method to characterize crowding in parafoveal vision (<3.5
      visual degrees) with spatial uncertainty. We find that eccentricity and hemifield
      have less impact on crowding than in the periphery, yet radial/tangential
      asymmetries are clearly preserved. There are considerable idiosyncratic
      differences observed between participants. The crowding factor method provides a
      powerful tool for examining crowding in central and peripheral vision, which will
      be useful in future studies that seek to understand visual processing under
      natural, active viewing conditions.

PMID- 27690172
TI  - Synthesis of Complex Druglike Molecules by the Use of Highly Functionalized Bench
      Stable Organozinc Reagents.
AB  - The reactivity of a representative set of 17 organozinc pivalates with 18
      polyfunctional druglike electrophiles (informers) in Negishi cross-coupling
      reactions was evaluated by high-throughput experimentation protocols. The high
      fidelity scaleup of successful reactions in parallel enabled the isolation of
      sufficient material for biological testing, thus demonstrating the high value of
      these new solid zinc reagents in a drug-discovery setting and potentially for
      many other applications in chemistry. Principal component analysis (PCA) clearly
      defined the independent roles of the zincates and the informers toward druggable
      space coverage.

PMID- 27690174
TI  - Sensitive Detection of Radiation-Induced Medulloblastomas after Acute or
      Protracted Gamma-Ray Exposures in Ptch1 Heterozygous Mice Using a Radiation
      Specific Molecular Signature.
AB  - Recently reported studies have led to a heightened awareness of the risks of
      cancer induced by diagnostic radiological imaging, and in particular, the risk of
      brain cancer after childhood CT scans. One feature of Ptch1+/- mice is their
      sensitivity to radiation-induced medulloblastomas (an embryonic cerebellar tumor)
      during a narrow window of time centered on the days around birth. Little is known
      about the dynamics of how dose protraction interacts with such narrow windows of
      sensitivity in individual tissues. Using medulloblastomas from irradiated Ptch1+/
      mice with a hybrid C3H * C57BL/6 F1 genetic background, we previously showed
      that the alleles retained on chromosome 13 (which harbors the Ptch1 gene) reveal
      two major mechanisms of loss of the wild-type allele. The loss of parental
      alleles from the telomere extending up to or past the Ptch1 locus by
      recombination (spontaneous type) accounts for almost all medulloblastomas in
      nonirradiated mice, while tumors in irradiated mice often exhibited interstitial
      deletions, which start downstream of the wild-type Ptch1 and extend up varying
      lengths towards the centromere (radiation type). In this study, Ptch1+/- mice
      were exposed to an acute dose of either 100 or 500 mGy gamma rays in utero or
      postnatally, or the same radiation doses protracted over a four-day period, and
      were monitored for medulloblastoma development. The results showed dose- and age
      dependent radiation-induced type tumors. Furthermore, the size of the radiation
      induced deletion differed with the dose rate. The results of this work suggest
      that tumor latency may be related to the size of the deletion. In this study, 500
      mGy exposure produced radiation-induced type tumors at all ages and dose rates,
      while 100 mGy exposure did not significantly produce radiation-induced type
      tumors. The radiation signature allows for unique mechanistic insight into the
      action of radiation to induce DNA lesions with known causal relationship to a
      specific tumor type, particularly for doses and dose rates that are relevant to
      both diagnostic and accidental radiological exposures.

PMID- 27690175
TI  - Risk of Hematologic Malignancies in the Offspring of Female Workers of the Mayak
      Nuclear Facility in the Southern Urals, Russian Federation.
AB  - Long-term effects of in utero exposure to ionizing radiation remain poorly
      quantified in humans. In this study, the risk of hematologic malignancies was
      investigated in offspring of female workers of the Mayak Production Association,
      a large Russian nuclear facility. Excess relative risks (ERR) for exposure to
      gamma radiation and plutonium were estimated in a cohort of 8,466 offspring who
      were born between January 1, 1948 and December 31, 1988 and followed until 2009.
      An unstable linear ERR of 1.12 (95% CI 0.11-3.44) per 100 mGy gamma exposure in
      utero was estimated based on 32 incident hematologic malignancies in 277,002
      person-years under risk. The ERR was increased in the dose category 20-79 mGy
      gamma exposure in utero (1.75, 95% CI 0.04; 5.63), while the other dose
      categories showed decreased or unstable estimates. Leukemia showed an ERR of 1.76
      (95% CI 0.01-8.33) per 100 mGy based on 13 cases. There was no consistent
      association with plutonium exposure. While an increased risk of hematologic
      malignancies after gamma exposure in utero was suggested, the small numbers
      prevented more definitive conclusions.

PMID- 27690176
TI  - The role of cognitive control mechanisms in selective attention towards emotional
      stimuli.
AB  - The role of cognitive control mechanisms in reducing interference from
      emotionally salient distractors was investigated. In two experiments,
      participants performed a flanker task in which target-distractor affective
      compatibility and cognitive load were manipulated. Differently from past studies,
      targets and distractors were presented at separate spatial locations and
      cognitive load was not domain-specific. In Experiment 1, words (positive vs.
      negative) and faces (angry, happy or neutral faces), were used respectively as
      targets and distractors, whereas in Experiment 2, both targets (happy vs. angry)
      and distractors were faces. Findings showed interference from distractor
      processing only when cognitive load was high. The present findings indicate that,
      when targets and distractors are presented at different spatial locations,
      cognitive control mechanisms are involved in preventing interference from
      positive (Exp. 1) or negative distractors (Exp. 2). The role of stimulus valence
      and type is also discussed with regard to different patterns of interference
      observed.

PMID- 27690173
TI  - Diffusion-weighted breast MRI: Clinical applications and emerging techniques.
AB  - : Diffusion-weighted MRI (DWI) holds potential to improve the detection and
      biological characterization of breast cancer. DWI is increasingly being
      incorporated into breast MRI protocols to address some of the shortcomings of
      routine clinical breast MRI. Potential benefits include improved differentiation
      of benign and malignant breast lesions, assessment and prediction of therapeutic
      efficacy, and noncontrast detection of breast cancer. The breast presents a
      unique imaging environment with significant physiologic and inter-subject
      variations, as well as specific challenges to achieving reliable high quality
      diffusion-weighted MR images. Technical innovations are helping to overcome many
      of the image quality issues that have limited widespread use of DWI for breast
      imaging. Advanced modeling approaches to further characterize tissue perfusion,
      complexity, and glandular organization may expand knowledge and yield improved
      diagnostic tools. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2016 J. Magn.
      Reson. Imaging 2017;45:337-355.

PMID- 27690178
TI  - Special issue of selected papers from the 2nd European Section Meeting of the
      International Academy of Cardiovascular Sciences held in Belgrade, Serbia, on 8
      10 October 2015 / Numero special d'articles selectionnes de la 2e reunion de la
      section europeenne de l'International Academy of Cardiovascular Sciences tenue a
      Belgrade (Serbie) du 8 au 10 octobre 2015.

PMID- 27690179
TI  - Preface.

PMID- 27690177
TI  - Antibiotic resistance and repetitive-element PCR fingerprinting in Aeromonas
      veronii isolates.
AB  - This study evaluated antibiotic resistance and the related genes in total 47
      Aeromonas veronii isolates from pet fish, eel (Anguilla japonica) and koi
      (Cyprinus carpio) in Korea. In comparison with the antibiotic susceptibilities of
      isolates from eel and koi, those of pet fish were more resistant to ceftiofur,
      aminoglycosides, tetracycline and nitrofurantoin. And isolates from pet fish
      showed high prevalences of class 1 integron, quinolones and tetracycline
      resistance determinants than those from eel and koi. Repetitive-element
      palindromic PCR (rep-PCR) showed larger diversities among A. veronii isolates.
      Collectively, pet fish may be a reservoir for multiple clones of A. veronii
      involved in antibiotic resistance. In this aspect, imported fish in the
      aquaculture trade should be steadily and continually screened for bacterial
      antibiotic resistance and related genes.

PMID- 27690180
TI  - Exopolymer production as a function of cell permeability and death in a diatom
      (Thalassiosira weissflogii) and a cyanobacterium (Synechococcus elongatus).
AB  - Exopolymer particles are found throughout the ocean and play a significant
      biogeochemical role in carbon cycling. Transparent exopolymer particles (TEP) are
      composed of acid polysaccharides, and Coomassie staining particles (CSP) are
      proteins. TEPs have been extensively studied in the ocean, while CSP have been
      largely overlooked. The objective of this research was to determine the role of
      stress and cell permeability in the formation of TEP and CSP. The diatom
      Thalassiosira weissflogii and cyanobacterium Synechococcus elongatus were grown
      in batch cultures and exposed to hydrogen peroxide (0, 10, and 100 MUM) as an
      environmental stressor. There was no correlation between TEP and CSP
      concentrations, indicating that they are different populations of particles
      rather than different chemical components of the same particles. CSP
      concentrations were not affected by hydrogen peroxide concentration and did not
      correlate with indicators of stress and cell death. In contrast, TEP
      concentrations in both taxa were correlated with a decrease in the effective
      quantum yield of photosystem II, increased activity of caspase-like enzymes, and
      an increase in the proportion of the population with permeable cell membranes,
      indicating that TEP production was associated with the process of cell death.
      These data show that different environmental factors and physiological processes
      affected the production of TEP and CSP by phytoplankton. TEP and CSP are separate
      populations of exopolymer particles with potentially different biogeochemical
      roles in the ocean.

PMID- 27690181
TI  - Harnessing the Lewis Acidity of HFIP through its Cooperation with a Calcium(II)
      Salt: Application to the Aza-Piancatelli Reaction.
AB  - A method to extend the scope of the aza-Piancatelli reaction between 2
      furylcarbinols and anilines is depicted. We found that 1,1,1,3,3,3-hexafluoro-2
      propanol (HFIP) is the solvent of choice for this transformation, as it
      outcompetes the usual solvents in terms of rate and yield. Side reactions and
      other issues raised by the title reaction are prevented, thereby providing an
      avenue to complex molecules that were previously inaccessible. Lewis acidity
      studies and computations were carried out to unveil the role of HFIP. Based on
      these results, we propose that HFIP is, in fact, acting as a Lewis acid and that
      its acidity can be enhanced when combined with a calcium(II) salt.

PMID- 27690182
TI  - Differences in treatment goals and perception of symptom burden between patients
      with myeloproliferative neoplasms (MPNs) and hematologists/oncologists in the
      United States: Findings from the MPN Landmark survey.
AB  - BACKGROUND: This analysis of the myeloproliferative neoplasm (MPN) Landmark
      survey evaluated gaps between patient perceptions of their disease management and
      physician self-reported practices. METHODS: The survey included 813 patient
      respondents who had MPNs (myelofibrosis [MF], polycythemia vera [PV], or
      essential thrombocythemia [ET]) and 457 hematologist/oncologist respondents who
      treated patients with these conditions. RESULTS: Greater proportions of physician
      respondents reported using prognostic risk classifications (MF, 83%; PV, 59%; ET,
      77%) compared with patient recollections (MF, 54%; PV, 17%; ET, 31%). Most
      physician respondents reported that their typical symptom assessments included
      asking patients about the most important symptoms or a full list of symptoms,
      whereas many patient respondents reported less specific assessments (eg, they
      were asked how they were feeling). Many patient respondents did not recognize
      common symptoms as MPN-related. For example, approximately one-half or more did
      not believe difficulty sleeping resulted from their MPN (MF, 49%; PV, 64%; ET,
      76%). Physician respondents underestimated the proportion of patients who had
      symptomatic PV or ET at diagnosis compared with patient respondents. There was
      discordance regarding treatment goals: among patient respondents with MF or PV,
      "slow/delay progression of condition" was the most important treatment goal,
      whereas physician respondents reported "symptom improvement" and "prevention of
      vascular/thrombotic events," respectively. Finally, more than one-third of
      patient respondents were not "very satisfied" with their physician's overall
      management/communication. CONCLUSIONS: The care and satisfaction of patients with
      MPN may be improved with increased patient education and improved patient
      physician communication. Cancer 2017;123:449-458. (c) 2016 The Authors. Cancer
      published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

PMID- 27690183
TI  - Bacterial Hyaluronidase Self-Triggered Prodrug Release for Chemo-Photothermal
      Synergistic Treatment of Bacterial Infection.
AB  - A novel platform for targeted on-demand prodrug ascorbic acid (AA) delivery is
      fabricated using a bacterial hyaluronidase sensitive graphene-mesoporous silica
      nanosheet@hyaluronic acid-magnetic nanoparticles as the nanocarrier to treat
      bacterial infections. The released AA can be converted to detrimental *OH in situ
      on the surface of bacteria. With the chemo-photothermal synergistic effect, the
      designed antibacterial system can effectively inactivate bacteria and disperse
      stubborn biofilm.

PMID- 27690185
TI  - Structure and temporal dynamics of the bacterial communities associated to
      microhabitats of the coral Oculina patagonica.
AB  - Corals are known to contain a diverse microbiota that plays a paramount role in
      the physiology and health of holobiont. However, few studies have addressed the
      variability of bacterial communities within the coral host. In this study,
      bacterial community composition from the mucus, tissue and skeleton of the
      scleractinian coral Oculina patagonica were investigated seasonally at two
      locations in the Western Mediterranean Sea, to further understand how
      environmental conditions and the coral microbiome structure are related. We used
      denaturing gradient gel electrophoresis in combination with next-generation
      sequencing and electron microscopy to characterize the bacterial community. The
      bacterial communities were significantly different among coral compartments, and
      coral tissue displayed the greatest changes related to environmental conditions
      and coral health status. Species belonging to the Rhodobacteraceae and
      Vibrionaceae families form part of O. patagonica tissues core microbiome and may
      play significant roles in the nitrogen cycle. Furthermore, sequences related to
      the coral pathogens, Vibrio mediterranei and Vibrio coralliilyticus, were
      detected not only in bleached corals but also in healthy ones, even during cold
      months. This fact opens a new view onto unveiling the role of pathogens in the
      development of coral diseases in the future.

PMID- 27690186
TI  - Substitutional limit of gadolinium in beta-tricalcium phosphate and its magnetic
      resonance imaging characteristics.
AB  - To compensate the limitations of bone tissue magnetic resonance imaging (MRI), a
      series of gadolinium (Gd3+ ) substituted beta-Tricalcium phosphate [beta-TCP,
      beta-Ca3 (PO4 )2 ] were developed. All the powders were characterized using XRD,
      Raman spectroscopy, Rietveld refinement of the XRD data and the studies confirmed
      the Gd3+ occupancy at Ca2+ (1), Ca2+ (2) and Ca2+ (3) lattice sites of beta-Ca3
      (PO4 )2. HR-TEM analysis revealed the spherical nature of particles with diameter
      about 100 nm. The Gd3+ doped beta-Ca3 (PO4 )2 exhibited non-toxic behaviour to MG
      63 cells in vitro and the room temperature magnetic field versus magnetization
      measurements confirmed its paramagnetic behaviour. MRI analysis revelas that it
      shorten both T1 and T2 proton relaxation times, thus influencing both r1 and r2
      relaxivity values that reach 61.97 mM-1 s-1 and 73.35 mM-1 s-1 . (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2545-2552,
      2017.

PMID- 27690184
TI  - Are reprogrammed cells a useful tool for studying dopamine dysfunction in
      psychotic disorders? A review of the current evidence.
AB  - Since 2006, reprogrammed cells have increasingly been used as a biomedical
      research technique in addition to neuro-psychiatric methods. These rapidly
      evolving techniques allow for the generation of neuronal sub-populations, and
      have sparked interest not only in monogenetic neuro-psychiatric diseases, but
      also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ)
      and bipolar disorder (BPD). This review provides a summary of 19 publications on
      reprogrammed adult somatic cells derived from patients with SCZ, and five
      publications using this technique in patients with BPD. As both disorders are
      complex and heterogeneous, there is a plurality of hypotheses to be tested in
      vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are
      sparse, despite the great explanatory power of the so-called DA hypothesis of
      SCZ. Some findings correspond to perturbations of cell energy metabolism, and
      observations in reprogrammed cells suggest neuro-developmental alterations. Some
      studies also report on the efficacy of medicinal compounds to revert alterations
      observed in cellular models. However, due to the paucity of replication studies,
      no comprehensive conclusions can be drawn from studies using reprogrammed cells
      at the present time. In the future, findings from cell culture methods need to be
      integrated with clinical, epidemiological, pharmacological and imaging data in
      order to generate a more comprehensive picture of SCZ and BPD.

PMID- 27690187
TI  - Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs.
AB  - Therapeutic nucleic acids hold great promise for the treatment of disease but
      require vectors for safe and effective delivery. Synthetic nanoparticle vectors
      composed of poly(beta-amino esters) (PBAEs) and nucleic acids have previously
      demonstrated potential utility for local delivery applications. To expand this
      potential utility to include systemic delivery of mRNA, hybrid polymer-lipid
      nanoformulations for systemic delivery to the lungs were developed. Through
      coformulation of PBAEs with lipid-polyethylene glycol (PEG), mRNA formulations
      were developed with increased serum stability and increased in vitro potency. The
      formulations were capable of functional delivery of mRNA to the lungs after
      intravenous administration in mice. To our knowledge, this is the first report of
      the systemic administration of mRNA for delivery to the lungs using degradable
      polymer-lipid nanoparticles.

PMID- 27690188
TI  - Machine-Washable Textile Triboelectric Nanogenerators for Effective Human
      Respiratory Monitoring through Loom Weaving of Metallic Yarns.
AB  - Textile triboelectric nanogenerators for human respiratory monitoring with
      machine washability are developed through loom weaving of Cu-PET and PI-Cu-PET
      yarns. Triboelectric charges are generated at the yarn crisscross intersections
      to achieve a maximum short circuit current density of 15.50 mA m-2 . By
      integrating into a chest strap, human respiratory rate and depth can be
      monitored.

PMID- 27690189
TI  - Synthesis and characterization of divinyl-fumarate poly-epsilon-caprolactone for
      scaffolds with controlled architectures.
AB  - A vinyl-terminated polycaprolactone has been developed for tissue engineering
      applications using a one-step synthesis and functionalization method based on
      ring opening polymerization (ROP) of epsilon-Caprolactone, with hydroxyl ethyl
      vinyl ether (HEVE) acting both as the initiator of ROP and as photo-curable
      functional group. The proposed method employs a catalyst based on aluminium,
      instead of the most popular Tin(II) 2-ethylhexanoate, to reduce the cytotoxicity.
      Following the synthesis of the vinyl-terminated polycaprolactone, its reaction
      with fumaryl chloride (FuCl) results in a divinyl-fumarate polycaprolactone
      (VPCLF). The polymers obtained were thoroughly characterized using Fourier
      transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC)
      techniques. The polymer has been successfully employed, in combination with N
      vinyl pyrrolidone (NVP), to fabricate films and computer-designed porous
      scaffolds by micro-stereolithography (MU-SL) with gyroid and diamond
      architectures. Characterization of the networks indicated the influence of NVP
      content on the network properties. Human mesenchymal stem cells adhered and
      spread onto VPCLF/NVP networks showing good biological properties and no
      cytotoxic effect. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27690190
TI  - Ferroelectric-Driven Performance Enhancement of Graphene Field-Effect Transistors
      Based on Vertical Tunneling Heterostructures.
AB  - A vertical graphene heterostructure field-effect transistor (VGHFET) using an
      ultrathin ferroelectric film as a tunnel barrier is developed. The
      heterostructure is capable of providing new degrees of tunability and
      functionality via coupling between the ferroelectricity and the tunnel current of
      the VGHFET, which results in a high-performance device. The results pave the way
      for developing novel atomic-scale 2D heterostructures and devices.

PMID- 27690191
TI  - Personality of young drivers in Oman: Relationship to risky driving behaviors and
      crash involvement among Sultan Qaboos University students.
AB  - OBJECTIVE: Drivers' behaviors such as violations and errors have been
      demonstrated to predict crash involvement among young Omani drivers. However,
      there is a dearth of studies linking risky driving behaviors to the personality
      of young drivers. The aim of the present study was to assess such traits within a
      sample of young Omani drivers (as measured through the behavioral inhibition
      system [BIS] and the behavioral activation system [BAS]) and determine links with
      aberrant driving behaviors and self-reported crash involvement. METHODS: A cross
      sectional study was conducted at the Sultan Qaboos University that targeted all
      licensed Omani's undergraduate students. A total of 529 randomly selected
      students completed the self-reported questionnaire that included an assessment of
      driving behaviors (e.g., Driver Behaviour Questionnaire, DBQ) as well as the
      BIS/BAS measures. RESULTS: A total of 237 participants (44.8%) reported
      involvement in at least one crash since being licensed. Young drivers with lower
      BIS-Anxiety scores and higher BAS-Fun Seeking tendencies as well as male drivers
      were more likely to report driving violations. Statistically significant gender
      differences were observed on all BIS and BAS subscales (except for BAS-Fun) and
      the DBQ subscales, because males reported higher trait scores. Though personality
      traits were related to aberrant driving behaviors at the bivariate level, the
      constructs were not predictive of engaging in violations or errors. Furthermore,
      consistent with previous research, a supplementary multivariate logistic
      regression analysis revealed that only driving experience was predictive of crash
      involvement. CONCLUSIONS: The findings highlight that though personality traits
      influence self-reported driving styles (and differ between the genders), the
      relationship with crash involvement is not as clear. This article further
      outlines the key findings of the study in regards to understanding core
      psychological constructs that increase crash risk.

PMID- 27690192
TI  - Systemic Collyriclum faba (Trematoda: Collyriclidae) Infection in a Wild Common
      Raven ( Corvus corax ).
AB  - A hatch-year Common Raven ( Corvus corax ) with subcutaneous and internal
      pseudocysts, filled with fluid, containing a pair of adult trematodes and
      numerous eggs consistent with Collyriclum faba, died near a riverbank in
      California, US. While C. faba is incidental in many Passeriformes, this case was
      a fatal systemic infection.

PMID- 27690193
TI  - How Respiratory Pathogens Contribute to Lamb Mortality in a Poorly Performing
      Bighorn Sheep ( Ovis canadensis ) Herd.
AB  - We evaluated bighorn sheep ( Ovis canadensis ) ewes and their lambs in captivity
      to examine the sources and roles of respiratory pathogens causing lamb mortality
      in a poorly performing herd. After seven consecutive years of observed December
      recruitments of <10%, 13 adult female bighorn sheep from the remnant Gribbles
      Park herd in Colorado, US were captured and transported to the Thorne-Williams
      Wildlife Research Center in Wyoming in March 2013. Ewes were sampled repeatedly
      over 16 mo. In April 2014, ewes were separated into individual pens prior to
      lambing. Upon death, lambs were necropsied and tested for respiratory pathogens.
      Six lambs developed clinical respiratory disease and one lamb was abandoned.
      Pathology from an additional six lambs born in 2013 was also evaluated.
      Mycoplasma ovipneumoniae , leukotoxigenic Mannheimia spp., leukotoxigenic
      Bibersteinia trehalosi , and Pasteurella multocida all contributed to lamb
      pneumonia. Histopathology suggested a continuum of disease, with lesions typical
      of pasteurellosis predominating in younger lambs and lesions typical of
      mycoplasmosis predominating in older lambs. Mixed pathology was observed in lambs
      dying between these timeframes. We suspected that all the ewes in our study were
      persistently infected and chronically shedding the bacteria that contributed to
      summer lamb mortality.

PMID- 27690194
TI  - PREVALENCE AND POTENTIAL IMPACT OF TOXOPLASMA GONDII ON THE ENDANGERED AMARGOSA
      VOLE (MICROTUS CALIFORNICUS SCIRPENSIS), CALIFORNIA, USA.
AB  - We investigated the prevalence of Toxoplasma gondii in 2011-15 to assess its
      potential threat on the endangered Amargosa vole ( Microtus californicus
      scirpensis) in California, US. Surveillance was simultaneously performed on
      populations of syntopic rodent species. We detected antibodies to T. gondii in
      sera from 10.5% of 135 wild-caught Amargosa voles; 8% of 95 blood samples were
      PCR-positive for the T. gondii B1 gene, and 5.0% of 140 sympatric rodent brain
      samples were PCR-positive. Exposure to T. gondii did not change the probability
      that an animal would be recaptured in the field study. Behavioral response to
      domestic cat ( Felis catus ) and bobcat ( Lynx rufus ) urine was evaluated in
      five nonendangered Owens Valley voles ( Microtus californicus vallicola) as
      surrogates for Amargosa voles and seven uninfected controls. Voles showed mild
      attraction to mouse urine and had neutral reactions to domestic cat urine whether
      or not infected. Time spent near bobcat urine was approximately twice as high in
      infected than in uninfected voles (although not statistically significant). The
      presence of T. gondii in wild Amargosa vole and sympatric rodent populations may
      hinder the endangered Amargosa vole population's ability to recover in the wild.

PMID- 27690195
TI  - Associations among Habitat Characteristics and Meningeal Worm Prevalence in
      Eastern South Dakota, USA.
AB  - Few studies have evaluated how wetland and forest characteristics influence the
      prevalence of meningeal worm ( Parelaphostrongylus tenuis ) infection of deer
      throughout the grassland biome of central North America. We used previously
      collected, county-level prevalence data to evaluate associations between habitat
      characteristics and probability of meningeal worm infection in white-tailed deer
      ( Odocoileus virginianus ) across eastern South Dakota, US. The highest-ranked
      binomial regression model for detecting probability of meningeal worm infection
      was spring temperature + summer precipitation + percent wetland; weight of
      evidence (wi=0.71) favored this model over alternative models, though predictive
      capability was low (Receiver operating characteristic=0.62). Probability of
      meningeal worm infection increased by 1.3- and 1.6-fold for each 1-cm and 1-C
      increase in summer precipitation and spring temperature, respectively. Similarly,
      probability of infection increased 1.2-fold for each 1% increase in wetland
      habitat. Our findings highlight the importance of wetland habitat in predicting
      meningeal worm infection across eastern South Dakota. Future research is
      warranted to evaluate the relationships between climatic conditions (e.g.,
      drought, wet cycles) and deer habitat selection in maintaining P. tenuis along
      the western boundary of the parasite.

PMID- 27690196
TI  - Studies on fluid dynamics of the flow field and gas transfer in orbitally shaken
      tubes.
AB  - Orbitally shaken cylindrical bioreactors [OrbShake bioreactors (OSRs)] without an
      impeller or sparger are increasingly being used for the suspension cultivation of
      mammalian cells. Among small volume OSRs, 50-mL tubes with a ventilated cap
      (OSR50), originally derived from standard laboratory centrifuge tubes with a
      conical bottom, have found many applications including high-throughput screening
      for the optimization of cell cultivation conditions. To better understand the
      fluid dynamics and gas transfer rates at the liquid surface in OSR50, we
      established a three-dimensional simulation model of the unsteady liquid forms
      (waves) in this vessel. The studies verified that the operating conditions have a
      large effect on the interfacial surface. The volumetric mass transfer coefficient
      (kL a) was determined experimentally and from simulations under various working
      conditions. We also determined the liquid-phase mass transfer coefficient (kL )
      and the specific interfacial area (a) under different conditions to demonstrate
      that the value of a affected the gas transfer rate more than did the value of kL
      . High oxygen transfer rates, sufficient for supporting the high-density culture
      of mammalian cells, were found. Finally, the average axial velocity of the liquid
      was identified to be an important parameter for maintaining cells in suspension.
      Overall these studies provide valuable insights into the preferable operating
      conditions for the OSR50, such as those needed for cell cultures requiring high
      oxygen levels. (c) 2016 American Institute of Chemical Engineers Biotechnol.
      Prog., 33:192-200, 2017.

PMID- 27690197
TI  - Special issue on electronic cigarettes.

PMID- 27690198
TI  - E-cigarette aerosols induce lower oxidative stress in vitro when compared to
      tobacco smoke.
AB  - Tobacco smoking is a risk factor for various diseases. The underlying cellular
      mechanisms are not fully characterized, but include oxidative stress, apoptosis,
      and necrosis. Electronic-cigarettes (e-cigarettes) have emerged as an alternative
      to and a possible means to reduce harm from tobacco smoking. E-cigarette vapor
      contains significantly lower levels of toxicants than cigarette smoke, but
      standardized methods to assess cellular responses to exposure are not well
      established. We investigated whether an in vitro model of the airway epithelium
      (human bronchial epithelial cells) and commercially available assays could
      differentiate cellular stress responses to aqueous aerosol extracts (AqE)
      generated from cigarette smoke and e-cigarette aerosols. After exposure to AqE
      concentrations of 0.063-0.500 puffs/mL, we measured the intracellular glutathione
      ratio (GSH:GSSG), intracellular generation of oxidant species, and activation of
      the nuclear factor erythroid-related factor 2 (Nrf2)-controlled antioxidant
      response elements (ARE) to characterize oxidative stress. Apoptotic and necrotic
      responses were characterized by increases in caspase 3/7 activity and reductions
      in viable cell protease activities. Concentration-dependent responses indicative
      of oxidative stress were obtained for all endpoints following exposure to
      cigarette smoke AqE: intracellular generation of oxidant species increased by up
      to 83%, GSH:GSSG reduced by 98.6% and transcriptional activation of ARE increased
      by up to 335%. Caspase 3/7 activity was increased by up to 37% and the viable
      cell population declined by up to 76%. No cellular stress responses were detected
      following exposure to e-cigarette AqE. The methods used were suitably sensitive
      to be employed for comparative studies of tobacco and nicotine products.

PMID- 27690199
TI  - Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco
      smoke.
AB  - Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm
      to public health caused by tobacco smoking by offering smokers a less harmful
      means of receiving nicotine. As e-cigarettes are a relatively new phenomenon,
      there are limited scientific data on the longer-term health effects of their use.
      This study describes a robust in vitro method for assessing the cytotoxic
      response of e-cigarette aerosols that can be effectively compared with
      conventional cigarette smoke. This was measured using the regulatory accepted
      Neutral Red Uptake assay modified for air-liquid interface (ALI) exposures. An
      exposure system, comprising a smoking machine, traditionally used for in vitro
      tobacco smoke exposure assessments, was adapted for use with e-cigarettes to
      expose human lung epithelial cells at the ALI. Dosimetric analysis methods using
      real-time quartz crystal microbalances for mass, and post-exposure chemical
      analysis for nicotine, were employed to detect/distinguish aerosol dilutions from
      a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes
      (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity
      than 3R4F cigarette smoke based on matched EC50 values at different dilutions
      (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1 MUg/cm2) and nicotine (0.89 vs. 0.27
      MUg/cm2), respectively. Test doses where cigarette smoke and e-cigarette aerosol
      cytotoxicity were observed are comparable with calculated daily doses in
      consumers. Such experiments could form the basis of a larger package of work
      including chemical analyses, in vitro toxicology tests and clinical studies, to
      help assess the safety of current and next generation nicotine and tobacco
      products.

PMID- 27690202
TI  - Erratum.

PMID- 27690200
TI  - Zika virus infection and pregnancy: what we do and do not know.
AB  - Recent data strongly suggest an association between the current outbreak of ZIKA
      virus (ZIKV) in many countries of Central and South America and a sharp increase
      in the detection of microcephaly and fetal malformations. The link with brain
      defect, which has been detected mainly in some areas of Brazil, is supported by
      the following evidence: (1) ZIKV transmission from infected pregnant women to
      their fetuses; (2) the potential of ZIKV to determine a specific congenital fetal
      syndrome characterized by abnormalities involving primarily the developing brain
      and eye. In particular, the risk of transmission and congenital disease appears
      to be restricted to mother's infection during the first trimester of pregnancy.
      Among brain defects, microcephaly, brain calcifications, and ventriculomegaly are
      the most frequent abnormalities of the central nervous system detected so far.
      However, relevant information on effect of maternal infection with ZIKV on the
      fetus is still limited. In this review, we focus our attention on current
      knowledge about ZIKV infection in pregnancy, discussing relevant issues and open
      problems which merit further investigation.

PMID- 27690204
TI  - Introduction to the special series: Technology and disabilities in education.
AB  - In the nearly 30 years since the passage of the Technology-Related Assistance to
      Individuals with Disabilities Act of 1988, technology-mediated instruction has
      been implemented successfully with both students without disabilities and
      students with a range of disabilities to help them meet the demands of
      instruction. In this special issue of Assistive Technology, a number of noted
      scholars contribute research findings designed to add to the growing body of
      knowledge validating the use of assistive and instructional technology in the
      classroom.

PMID- 27690203
TI  - Practice Guidelines for Teledermatology.
AB  - Previous American Telemedicine Association (ATA) Teledermatology Practice
      Guidelines were issued in 2007. This updated version reflects new knowledge in
      the field, new technologies, and the need to incorporate teledermatology practice
      in a variety of settings, including hospitals, urgent care centers, Federally
      Qualified Health Centers, school-based clinics, public health facilities, and
      patient homes.

PMID- 27690205
TI  - Baseline adiponectin and leptin levels in predicting an increased risk of disease
      activity in rheumatoid arthritis: A meta-analysis and systematic review.
AB  - To determine the pathogenic role of adipokines, such as adiponectin and leptin,
      in rheumatoid arthritis (RA) by investigating whether serum levels of these
      adipokines correlated with disease activity in RA patients. Medline, Cochrane,
      EMBASE and Google Scholar were searched for studies published until 5 November
      2015 reporting serum levels of leptin and adiponectin and measures of disease
      activity including DAS scores and radiographic progression scores (such as total
      change in SHS scores and number of erosions). Secondary outcomes included pain
      scores, functional status and health questionnaires. Only randomized controlled
      trials, cohort studies, or two-armed prospective or retrospective studies were
      included. A chi2-based test of homogeneity was performed using Cochran's Q
      statistic and I2. A total of 917 predominantly female participants (average age
      range, 39-56 years) from six prospective cohort studies were included for
      assessment. A fixed-effects analysis was applied for leptin levels due to lack of
      heterogeneity among the studies (Q = 4.4364; I2 = 32.38). A random-effects
      analysis was applied to serum levels of adiponectin because of significant
      heterogeneity between studies (Q = 4.444, I2 = 77.50%). Serum leptin levels were
      higher in RA patients with high disease activity (pooled SMD: 0.53, 95% CI: 0.24
      0.82); however, serum adiponectin levels did not correlate with RA disease
      activity (pooled OR: 1.38, 95% CI: 0.77-2.47). The meta-analysis provides an
      additional factor to determine high disease activity index in RA, that is, serum
      leptin levels, which can be of benefit when choosing treatment strategies.

PMID- 27690206
TI  - The Interaction of Obesity and Nocturnal Hypoxemia on Cardiovascular Consequences
      in Adults with Suspected Obstructive Sleep Apnea. A Historical Observational
      Study.
AB  - RATIONALE: The interrelationships between obstructive sleep apnea (OSA) and
      obesity are complex and bidirectional; however, current evidence regarding their
      combined effect on cardiovascular risk is limited and conflicting. Animal studies
      suggest that obesity may exacerbate the cardiovascular consequences of
      intermittent hypoxemia. OBJECTIVES: In this historical observational study, we
      investigated whether obesity increases the effect of nocturnal hypoxemia on the
      incidence of cardiovascular events in adults with suspected OSA. METHODS: All
      adults with suspected OSA who underwent diagnostic polysomnography at a large
      academic hospital between 1994 and 2010 were linked to provincial health
      administrative data to determine a composite cardiovascular outcome
      (hospitalization due to heart failure, myocardial infarction, stroke, or
      revascularization procedures). Using a competing-risk model and controlling for
      confounders, hazards were compared between four groups: group 1 comprised obese
      patients (body mass index >30 kg/m2) with oxygen desaturation (>9 min of sleep
      spent with SaO2 <90%); group 2 comprised obese patients without desaturation;
      group 3 comprised nonobese patients with desaturation; and group 4 comprised
      nonobese patients without desaturation. Interaction was measured using the
      relative excess risk due to interaction. MEASUREMENTS AND MAIN RESULTS: A total
      of 10,149 participants were followed, with 17%, 25%, 8%, and 50% in groups 1-4,
      respectively. Over a median of 7.8 years, 896 (8.8%) first cardiovascular events
      occurred. Group 1 was associated with the highest hazard compared with the other
      groups, using group 4 as a reference (hazard ratio [HR] for group 1, 1.84; 95%
      confidence interval [CI], 1.46-2.32; HR for group 2, 1.59, 95% CI, 1.29-1.95; HR
      for group 3, 1.51; 95% CI, 1.15-1.98). The relative excess risk due to
      interaction was -0.25 (95% CI, -0.78 to 0.27), indicating no interaction.
      CONCLUSIONS: In adults with suspected OSA, the highest cardiovascular risk was
      found in obese patients with nocturnal oxygen desaturation; however, the effect
      of these two factors together does not exceed the effect of each factor
      considered individually.

PMID- 27690207
TI  - Prehospital Nitroglycerin in Tachycardic Chest Pain Patients: A Risk for
      Hypotension or Not?
AB  - BACKGROUND: The American Heart Association guidelines (AHA) guidelines list
      tachycardia as a contraindication for the administration of nitroglycerin (NTG),
      despite limited evidence of adverse events. We sought to determine whether NTG
      administered for chest pain was a predictor of hypotension (systolic blood
      pressure <90 mmHg) in patients with tachycardia, compared to patients without
      tachycardia (50>= heart rate <=100). METHODS: We performed a retrospective cohort
      study using patient care reports completed by basic life support (BLS) providers
      in a large urban Canadian EMS system for the period 2010-2012. We used logistic
      regression to test the association between post-NTG hypotension and tachycardia,
      independent of pre-NTG blood pressure, age, sex, and comorbidities. Using
      identical models, we tested four secondary outcomes (drop in blood pressure,
      reduced consciousness, bradycardia, and cardiac arrest). RESULTS: The cohort
      included 10,308 patients who were administered NTG by BLS in the prehospital
      setting; 2,057 (20%) of patients were tachycardic before NTG administration.
      Hypotension occurred in 320 of all patients (3.1%): 239 without tachycardia
      (2.9%) and 81 with tachycardia (3.9%). Compared to non-tachycardic patients,
      tachycardic patients showed increased adjusted odds of hypotension (AOR: 1.60;
      95% CI: 1.23-2.08) or of a drop in blood pressure of 30mm Hg or greater (AOR:
      1.11; CI: 1.00-1.24). Tachycardia was associated with decreased odds of
      bradycardia (OR: 0.33; CI: 0.17-0.64). We did not find a significant association
      between tachycardia and either post-NTG reduced level of consciousness or cardiac
      arrest. We did find a strong, significant association between pre-NTG blood
      pressure and post-NTG hypotension (AOR for units of 10mmHg: 0.64; CI: 0.61-0.69).
      CONCLUSION: Hypotension following prehospital administration of NTG was
      infrequent in patients with chest pain. However, while the absolute risk of NTG
      induced hypotension was low, patients with pre-NTG tachycardia had a significant
      increase in the relative risk of hypotension. In addition, hypotension occurred
      most frequently in patients presenting with a lower pre-NTG blood pressure, which
      may prove to be a more discriminating basis for future guidelines. EMS medical
      directors should review BLS chest pain protocols to weigh the benefits of NTG
      administration against its risks.

PMID- 27690208
TI  - Genomic feature extraction and comparison based on global alignment of ChIP
      sequencing data.
AB  - Enhanced accuracy and high-throughput capability in capturing genetic activities
      lead ChIP-sequencing technology to be applied prevalently in diverse study for
      tackling DNA-protein interaction problems. Till now, such questions as deciding
      suitable ChIP-seq arguments and comparing sample quality still haunt biologists.
      We propose the methods for answering such questions as deciding optimal argument
      pairs in global alignment of ChIP sequencing data; then we employ a modern signal
      processing approach to extract inherent genomic features from the global
      alignments of transcriptional binding activities; together with pairwise
      comparison from intra- and inter-sample perspectives; thus we can further
      determine alignment quality and decide the optimal candidate for multi-source
      heterogeneous high-throughput sequences. The work provides a practical approach
      to quantitatively compare the alignment quality for heterogeneous sequencing
      data, especially in determining the efficiency of transcriptional binding from
      replicate samples, thus it helps to exploit the potentiality of ChIP-seq for deep
      comprehension of inherent biological meanings from the high-throughput genomic
      sequences.

PMID- 27690209
TI  - Characterization of the transcriptomes and cuticular protein gene expression of
      alate adult, brachypterous neotenic and adultoid reproductives of Reticulitermes
      labralis.
AB  - The separation of primary reproductive and secondary reproductive roles based on
      the differentiation of alate adults and neotenic reproductives is the most
      prominent characteristic of termites. To clarify the mechanism underlying this
      differentiation, we sequenced the transcriptomes of alate adults (ARs),
      brachypterous neotenics (BNs) and adultoid reproductives (ANs) from the last
      instar nymphs of Reticulitermes labralis. A total of 404,152,188 clean sequencing
      reads was obtained and 61,953 unigenes were assembled. Of the 54 identified
      cuticular protein (CP) genes of the reproductives, 22 were classified into the
      CPR family and 7 were classified into the CPG family. qRT-PCR analyses of the 6
      CP genes revealed that the CP genes involved in exocuticle sclerotization were
      highly expressed in the ARs and RR-1 involved in soft endocuticle was highly
      expressed in the ARs and ANs. These results suggest that the alate adults might
      increase cuticular component deposition to adapt to new or changing environments
      and that the development of reproductive individuals into primary or secondary
      reproductives is controlled by the expression of cuticular protein genes involved
      in the hardening of the exocuticle. In addition, the AN caste is a transitional
      type between the BN and AR castes in the process of evolution.

PMID- 27690210
TI  - A systematic review of trial registration and selective outcome reporting in
      psychotherapy randomized controlled trials.
AB  - OBJECTIVE: Selective outcome reporting poses serious implications on our evidence
      base for best practice. The extent to which selective outcome reporting and trial
      registration occurs in the wider psychotherapy literature needs to be
      investigated. METHOD: Randomized controlled psychotherapy trials published
      between 2010 and 2014 were selected from the five highest impact factor journals
      in clinical psychology that publish clinical trials. Data on primary and
      secondary outcomes, funding, and participant numbers were extracted from the
      article and registry and compared. RESULTS: From 112 trials, 67 (59.8%) were
      registered, 27 (24.1%) were prospectively registered, and only 13 (11.6%) were
      correctly registered and reported. Seven of these 13 trials showed evidence of
      selective outcome reporting, of which four had discrepancies favoring significant
      outcomes. One of the remaining six trials changed their primary outcomes during
      participant enrollment. Overall, only five (4.5%) trials were free from selective
      outcome reporting. Three of these five trials had more than a 10% change between
      planned and achieved sample size. Funding was not associated with correct
      registration or reporting. CONCLUSIONS: The proportion of psychotherapy
      randomized controlled trials correctly registered and transparently reported is
      poor. Psychologists should consider the impact these results have on public
      confidence in reported outcomes.

PMID- 27690211
TI  - Self-Assembly and Conformational Changes of Hydrophobin Classes at the Air-Water
      Interface.
AB  - We use surface-specific vibrational sum-frequency generation spectroscopy (VSFG)
      to study the structure and self-assembling mechanism of the class I hydrophobin
      SC3 from Schizophyllum commune and the class II hydrophobin HFBI from Trichoderma
      reesei. We find that both hydrophobins readily accumulate at the water-air
      interface and form rigid, highly ordered protein films that give rise to
      prominent VSFG signals. We identify several resonances that are associated with
      beta-sheet structures and assign them to the central beta-barrel core present in
      both proteins. Differences between the hydrophobin classes are observed in their
      interfacial self-assembly. For HFBI, we observe no changes in conformation upon
      adsorption to the water surface. For SC3, we observe an increase in beta-sheet
      specific signals that supports a surface-driven self-assembly mechanism in which
      the central beta-barrel remains intact and stacks into a larger-scale
      architecture, amyloid-like rodlets.

PMID- 27690212
TI  - DNA Polymerase-Directed Hairpin Assembly for Targeted Drug Delivery and Amplified
      Biosensing.
AB  - Due to the predictable conformation and programmable Watson-Crick base-pairing
      interactions, DNA has proven to be an attractive material to construct various
      nanostructures. Herein, we demonstrate a simple model of DNA polymerase-directed
      hairpin assembly (PDHA) to construct DNA nanoassemblies for versatile
      applications in biomedicine and biosensing. The system consists of only two
      hairpins, an initiator and a DNA polymerase. Upon addition of aptamer-linked
      initiator, the inert stems of the two hairpins are activated alternately under
      the direction of DNA polymerase, which thus grows into aptamer-tethered DNA
      nanoassemblies (AptNAs). Moreover, through incorporating fluorophores and drug
      loading sites into the AptNAs, we have constructed multifunctional DNA
      nanoassemblies for targeted cancer therapy with high drug payloads and good
      biocompatibility. Interestingly, using the as-prepared AptNAs as building blocks,
      DNA nanohydrogels are self-assembled after centrifugation driven by liquid
      crystallization and dense packaging of DNA duplexes. Taking advantage of easy
      preparation and high loading capacity, the PDHAs are readily extended to the
      fabrication of a label-free biosensing platform, achieving amplified
      electrochemical detection of microRNA-21 (miR-21) with a detection limit as low
      as 0.75 fM and a dynamic range of 8 orders of magnitude. This biosensor also
      demonstrates excellent specificity to discriminate the target miR-21 from the
      control microRNAs and even the one-base mismatched one and further performs well
      in analyzing miR-21 in MCF-7 tumor cells.

PMID- 27690213
TI  - Natural and induced direct reprogramming: mechanisms, concepts and general
      principles-from the worm to vertebrates.
AB  - Elucidating the mechanisms underlying cell fate determination, cell identity
      maintenance and cell reprogramming in vivo is one of the main challenges in
      today's science. Such knowledge of fundamental importance will further provide
      new leads for early diagnostics and targeted therapy approaches both in
      regenerative medicine and cancer research. This review focuses on recent
      mechanistic findings and factors that influence the differentiated state of cells
      in direct reprogramming events, aka transdifferentiation. In particular, we will
      look at the mechanistic and conceptual advances brought by the use of the
      nematode Caenorhabditis elegans and highlight common themes across phyla.

PMID- 27690214
TI  - Low Pretreatment Acoustic Radiation Force Impulse Imaging (ARFI) Values Predict
      Sustained Virological Response in Antiviral Hepatitis C Virus (HCV) Therapy.
AB  - BACKGROUND Non-invasive procedures such as acoustic radiation force impulse
      imaging (ARFI) shear-wave elastography are currently used for the assessment of
      liver fibrosis. In the course of chronic hepatitis C, significant liver fibrosis
      or cirrhosis develops in approximately 25% of patients, which is a negative
      predictor of antiviral treatment response. Cirrhosis can be prevented by
      successful virus elimination. In this prospective study, a pretreatment ARFI
      cutoff value of 1.5 m/s was evaluated in relation to sustained virological
      response to anti-HCV therapy. MATERIAL AND METHODS In 23 patients with chronic
      hepatitis C, liver stiffness was examined with ARFI at defined times before and
      under antiviral triple therapy (peginterferon, ribavirin in combination with a
      first-generation protease inhibitor, and telaprevir or boceprevir). Patients were
      stratified into 2 groups based on pretreatment ARFI values (<1.5 m/s and >=1.5
      m/s) for the assessment of virological response. RESULTS The liver stiffness at
      baseline for all patients was 1.57+/-0.79 m/s (ARFI median +/- standard
      deviation; margin: 0.81 m/s to 3.45 m/s). At week 4 of triple therapy, patients
      with low pretreatment ARFI values had higher rates of HCV-RNA negativity (69% vs.
      43%), reflecting an early rapid virological response (eRVR). Sustained
      virological response (SVR) was found in 75% (12/16) of patients with an ARFI
      value <1.5 m/s and only 57% (4/7) of patients with ARFI value >=1.5 m/s.
      CONCLUSIONS Patients with chronic hepatitis C and pretreatment ARFI <1.5 m/s
      showed earlier virus elimination and better response to treatment.

PMID- 27690215
TI  - The nullifying experience of self-objectification: The development and
      psychometric evaluation of the Self-Objectification Scale.
AB  - Self-objectification is a process or state in which an individual loses his/her
      sense of subjectivity. Although several measures assess self-objectification as
      representing self-perception based on sexual and bodily appearance, there is a
      need for a measure assessing self-objectification as reflecting dehumanization.
      This study aims to evaluate the psychometric properties of a new measure, the
      Self-Objectification Scale (SOS). In Study 1, the SOS was administered to 373
      students. In Study 2, the SOS was administered to 300 female students along with
      a battery of questionnaires, including the Experience of Shame Scale (ESS) and
      the Objectified Body Consciousness Scale (OBC). In addition, participants were
      asked about their history of childhood maltreatment, via the Childhood Trauma
      Questionnaire (CTQ), as well as about their experience of sexual and/or physical
      assault, at any age. Two reliable SOS subscales emerged from Study 1:
      Invisibility and Lack of Autonomy. In Study 2, a confirmatory factor analysis
      confirmed the scale's underlying factor structure, which was obtained in Study 1.
      The two factors were significantly correlated with measures of shame and body
      objectification. Finally, individuals who reported childhood maltreatment, as
      well as those who reported sexual and/or physical assault at any age, had higher
      scores of Invisibility and Lack of Autonomy than those who did not have such
      experiences. The results of the present analyses suggest that the SOS has good
      psychometric properties, making it useful as an assessment tool in future
      research.

PMID- 27690216
TI  - Victimization and psychopathic features in a population-based sample of Finnish
      adolescents.
AB  - We examined different forms of victimization experiences in relation to
      psychopathic features and whether these associations differed in boys and girls
      among 4855 Finnish school adolescents aged 15-16 years. Psychopathic features
      were measured with the Antisocial Process Screening Device- Self Report (APSD
      SR). Victimization was assessed with questions about violent and abusive
      experiences across lifetime and within the last 12 months. Results from linear
      regression analysis showed that victimization was significantly associated with
      higher APSD-SR total scores, more strongly in girls than boys. Recent (12-month)
      victimization showed significance in the relationship between victimization and
      psychopathic features; especially recent sexual abuse and parental corporal
      punishment were strong determinants of higher APSD-SR total scores. The present
      study demonstrates novel findings on how severe victimization experiences relate
      to psychopathic features in community youth, especially in girls. The findings
      underscore the need for comprehensive evaluation of victimization experiences
      when psychopathic features are present in youth.

PMID- 27690217
TI  - The p53 status can influence the role of Sam68 in tumorigenesis.
AB  - The expression and activities of RNA binding proteins are frequently dysregulated
      in human cancer. Their roles, however, appears to be complex, with reports
      indicating both pro-tumorigenic and tumor suppressive functions. Here we show,
      using two classical mouse cancer models, that the role of KH-type RNA binding
      protein, Sam68, in tumor development can be influenced by the status of the p53
      tumor suppressor. We demonstrate that in mice expressing wild type p53, Sam68
      deficiency resulted in a higher incidence and malignancy of carcinogen-induced
      tumors, suggesting a tumor suppressive role for Sam68. In marked contrast, Sam68
      haploinsufficiency significantly delayed the onset of tumors in mice lacking p53
      and prolonged their survival, indicating that Sam68 accelerates the development
      of p53-deficient tumors. These findings provide considerable insight into a
      previously unknown relationship between Sam68 and the p53 tumor suppressor in
      tumorigenesis.

PMID- 27690218
TI  - Prognostic significance of BRCA mutations in ovarian cancer: an updated
      systematic review with meta-analysis.
AB  - There is no consensus on the syntheses concerning the impact of BRCA mutation on
      ovarian cancer survival. A systematic review and meta-analysis of observational
      studies was conducted that evaluated the impact of BRCA mutations on the survival
      outcomes of patients with ovarian cancer. The primary outcome measure was overall
      survival (OS) and secondary outcome was progression-free survival (PFS). We
      presented data with hazard ratios (HRs) and 95% confidence interval (CI) and
      pooled them using the random-effects models. From 2,624 unique records, 34
      eligible studies including 18,396 patients were identified. BRCA1/2 mutations
      demonstrated both OS and PFS benefits in patients with ovarian cancer (OS: HR =
      0.67, 95% CI, 0.57 to 0.78, I2 = 76.5%, P <0.001; PFS: HR = 0.62, 95% CI, 0.53 to
      0.73, I2 = 18.1%, P = 0.261). For BRCA1 mutation carriers, the HRs for OS and PFS
      benefits were 0.73 (95% CI, 0.63 to 0.86) and 0.68 (95% CI, 0.52 to 0.89),
      respectively. For BRCA2 mutation carriers, the HRs for OS and PFS benefits were
      0.57 (95% CI, 0.45 to 0.73) and 0.48 (95% CI, 0.30 to 0.75), respectively. The
      results of subgroup analyses for OS stratified by study quality, tumor stage,
      study design, sample size, number of research center, duration of follow-up,
      baseline characteristics adjusted and tumor histology were mostly constant across
      BRCA1/2, BRCA1 and BRCA2 mutation subtypes. In summary, for patients with ovarian
      cancer, BRCA mutations were associated with improved OS and PFS. Further large
      scale prospective cohort studies should be conducted to test its benefits in
      specific patients.

PMID- 27690219
TI  - MK-8776, a novel chk1 kinase inhibitor, radiosensitizes p53-defective human tumor
      cells.
AB  - Radiotherapy is commonly used to treat a variety of solid tumors but improvements
      in the therapeutic ratio are sorely needed. The aim of this study was to assess
      the Chk1 kinase inhibitor, MK-8776, for its ability to radiosensitize human tumor
      cells. Cells derived from NSCLC and HNSCC cancers were tested for
      radiosensitization by MK-8776. The ability of MK-8776 to abrogate the radiation
      induced G2 block was determined using flow cytometry. Effects on repair of
      radiation-induced DNA double strand breaks (DSBs) were determined on the basis of
      rad51, gamma-H2AX and 53BP1 foci. Clonogenic survival analyses indicated that MK
      8776 radiosensitized p53-defective tumor cells but not lines with wild-type p53.
      Abrogation of the G2 block was evident in both p53-defective cells and p53 wild
      type lines indicating no correlation with radiosensitization. However, only p53
      defective cells entered mitosis harboring unrepaired DSBs. MK-8776 appeared to
      inhibit repair of radiation-induced DSBs at early times after irradiation. A
      comparison of MK-8776 to the wee1 inhibitor, MK-1775, suggested both similarities
      and differences in their activities. In conclusion, MK-8776 radiosensitizes tumor
      cells by mechanisms that include abrogation of the G2 block and inhibition of DSB
      repair. Our findings support the clinical evaluation of MK-8776 in combination
      with radiation.

PMID- 27690220
TI  - Vemurafenib-resistant BRAF-V600E-mutated melanoma is regressed by MEK-targeting
      drug trametinib, but not cobimetinib in a patient-derived orthotopic xenograft
      (PDOX) mouse model.
AB  - Melanoma is a recalcitrant disease. The present study used a patient-derived
      orthotopic xenograft (PDOX) model of melanoma to test sensitivity to three
      molecularly-targeted drugs and one standard chemotherapeutic. A BRAF-V600E-mutant
      melanoma obtained from the right chest wall of a patient was grown orthotopically
      in the right chest wall of nude mice to establish a PDOX model. Two weeks after
      implantation, 50 PDOX nude mice were divided into 5 groups: G1, control without
      treatment; G2, vemurafenib (VEM) (30 mg/kg); G3; temozolomide (TEM) (25 mg/kg);
      G4, trametinib (TRA) (0.3 mg/kg); and G5, cobimetinib (COB) (5 mg/kg). Each drug
      was administered orally, daily for 14 consecutive days. Tumor sizes were measured
      with calipers twice a week. On day 14 from initiation of treatment, TRA, an MEK
      inhibitor, was the only agent of the 4 tested that caused tumor regression (P <
      0.001 at day 14). In contrast, another MEK inhibitor, COB, could slow but not
      arrest growth or cause regression of the melanoma. First-line therapy TEM could
      slow but not arrest tumor growth or cause regression. The patient in this study
      had a BRAF-V600E-mutant melanoma and would be considered to be a strong candidate
      for VEM as first-line therapy, since VEM targets this mutation. However, VEM was
      not effective. The PDOX model thus helped identify the very-high efficacy of TRA
      against the melanoma PDOX and is a promising drug for this patient. These results
      demonstrate the powerful precision of the PDOX model for cancer therapy, not
      achievable by genomic analysis alone.

PMID- 27690221
TI  - RAB22A overexpression promotes the tumor growth of melanoma.
AB  - Malignant melanoma is the most aggressive type of skin cancer. RAB22A, a member
      of RAS oncogene family, has been found to be significantly upregulated in
      multiple human cancers. In the present study, we found that RAB22A mRNA
      expression was significantly upregulated in melanoma tissues (including 60
      primary melanomas and 84 metastatic melanomas) compared to benign nevi (n = 20),
      which were significantly higher in metastatic melanoma tissues than primary
      tissues. Immunohistochemistry data further showed that the positive
      immunoreactivity of RAB22A was detected in 66% (95/144) melanoma tissues, but not
      in benign nevi. Moreover, high expression of RAB22A was significantly associated
      with advanced clinical stage in melanoma. Furthermore, patients with high RAB22A
      expression had shorter overall survival compared those with low expression of
      RAB22A. In-vitro study showed that RAB22A was also upregulated in melanoma cell
      lines WM35, A375, WM451, and SK-MEL-1, when compared with the normal melanocyte
      HM cells. Knockdown of RAB22A significantly reduced the proliferation, migration
      and invasion of melanoma A375 cells, while overexpression of RAB22A significantly
      promoted these malignant phenotypes. In addition, RAB22A was found to be a target
      of miR-203, a tumor suppressive miRNA in melanoma. Besides, miR-203 was
      downregulated in melanoma tissues and cell lines, when compared with benign nevi
      and HM cells, respectively. Taken these findings together, our study could
      validate an oncogenic role of RAB22A in melanoma, suggesting that RAB22A may be a
      potential therapeutic target for melanoma.

PMID- 27690222
TI  - Identification of Anthropogenic CO2 Using Triple Oxygen and Clumped Isotopes.
AB  - Quantification of contributions from various sources of CO2 is important for
      understanding the atmospheric CO2 budget. Considering the number and diversity of
      sources and sinks, the widely used proxies such as concentration and conventional
      isotopic compositions (delta13C and delta18O) are not always sufficient to fully
      constrain the CO2 budget. Additional constraints may help in understanding the
      mechanisms of CO2 production and consumption. The anomaly in triple oxygen
      isotopes or 17O excess (denoted by Delta17O) and molecules containing two rare
      isotopes, called clumped isotopes, are two recently developed tracers with
      potentials to independently constrain some important processes that regulate CO2
      in the atmosphere. The clumped isotope for CO2, denoted by Delta47, is the excess
      of 13C16O18O over a random distribution of isotopes in a CO2 molecule. We
      measured the concentrations of delta13C, delta18O, Delta17O, and Delta47 in air
      CO2 samples collected from the Hsuehshan tunnel (length: 12.9 km), and applied
      linear and polynomial regressions to obtain the fossil fuel end-members for all
      these isotope proxies. The other end-members, the values of all these proxies for
      background air CO2, are either assumed or taken as the values obtained over the
      tunnel and ocean. The fossil fuel (anthropogenic) CO2 end-member values for
      delta13C, delta18O, Delta17O, and Delta47 are estimated using the two component
      mixing approach: the derived values are -26.76 +/- 0.250/00, 24.57 +/- 0.330/00, 
      0.219 +/- 0.0210/00, and 0.267 +/- 0.0360/00, respectively. These four major CO2
      isotope tracers along with the concentration were used to estimate the
      anthropogenic contribution in the atmospheric CO2 in urban and suburban
      locations. We demonstrate that Delta17O and Delta47 have the potential to
      independently estimate anthropogenic contribution, and the advantages of these
      two over the conventional isotope proxies are discussed.

PMID- 27690223
TI  - Temporal proteomic analysis of HIV infection reveals remodelling of the host
      phosphoproteome by lentiviral Vif variants.
AB  - Viruses manipulate host factors to enhance their replication and evade cellular
      restriction. We used multiplex tandem mass tag (TMT)-based whole cell proteomics
      to perform a comprehensive time course analysis of >6500 viral and cellular
      proteins during HIV infection. To enable specific functional predictions, we
      categorized cellular proteins regulated by HIV according to their patterns of
      temporal expression. We focussed on proteins depleted with similar kinetics to
      APOBEC3C, and found the viral accessory protein Vif to be necessary and
      sufficient for CUL5-dependent proteasomal degradation of all members of the B56
      family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E).
      Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif
      dependent hyperphosphorylation of >200 cellular proteins, particularly substrates
      of the aurora kinases. The ability of Vif to target PPP2R5 subunits is found in
      primate and non-primate lentiviral lineages, and remodeling of the cellular
      phosphoproteome is therefore a second ancient and conserved Vif function.

PMID- 27690224
TI  - Critical roles of mTOR Complex 1 and 2 for T follicular helper cell
      differentiation and germinal center responses.
AB  - T follicular helper (Tfh) cells play critical roles for germinal center responses
      and effective humoral immunity. We report here that mTOR in CD4 T cells is
      essential for Tfh differentiation. In Mtorf/f-Cd4Cre mice, both constitutive and
      inducible Tfh differentiation is severely impaired, leading to defective germinal
      center B cell formation and antibody production. Moreover, both mTORC1 and mTORC2
      contribute to Tfh and GC B cell development but may do so via distinct
      mechanisms. mTORC1 mainly promotes CD4 T cell proliferation to reach the cell
      divisions necessary for Tfh differentiation, while Rictor/mTORC2 regulates Tfh
      differentiation by promoting Akt activation and TCF1 expression without grossly
      influencing T cell proliferation. Together, our results reveal crucial but
      distinct roles for mTORC1 and mTORC2 in CD4 T cells during Tfh differentiation
      and germinal center responses.

PMID- 27690225
TI  - Ongoing resolution of duplicate gene functions shapes the diversification of a
      metabolic network.
AB  - The evolutionary mechanisms leading to duplicate gene retention are well
      understood, but the long-term impacts of paralog differentiation on the
      regulation of metabolism remain underappreciated. Here we experimentally dissect
      the functions of two pairs of ancient paralogs of the GALactose sugar utilization
      network in two yeast species. We show that the Saccharomyces uvarum network is
      more active, even as over-induction is prevented by a second co-repressor that
      the model yeast Saccharomyces cerevisiae lacks. Surprisingly, removal of this
      repression system leads to a strong growth arrest, likely due to overly rapid
      galactose catabolism and metabolic overload. Alternative sugars, such as
      fructose, circumvent metabolic control systems and exacerbate this phenotype. We
      further show that S. cerevisiae experiences homologous metabolic constraints that
      are subtler due to how the paralogs have diversified. These results show how the
      functional differentiation of paralogs continues to shape regulatory network
      architectures and metabolic strategies long after initial preservation.

PMID- 27690227
TI  - Dynamic control of gene regulatory logic by seemingly redundant transcription
      factors.
AB  - Many transcription factors co-express with their homologs to regulate identical
      target genes, however the advantages of such redundancies remain elusive. Using
      single-cell imaging and microfluidics, we study the yeast general stress response
      transcription factor Msn2 and its seemingly redundant homolog Msn4. We find that
      gene regulation by these two factors is analogous to logic gate systems. Target
      genes with fast activation kinetics can be fully induced by either factor,
      behaving as an 'OR' gate. In contrast, target genes with slow activation kinetics
      behave as an 'AND' gate, requiring distinct contributions from both factors, upon
      transient stimulation. Furthermore, such genes become an 'OR' gate when the input
      duration is prolonged, suggesting that the logic gate scheme is not static but
      rather dependent on the input dynamics. Therefore, Msn2 and Msn4 enable a time
      based mode of combinatorial gene regulation that might be applicable to
      homologous transcription factors in other organisms.

PMID- 27690226
TI  - Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with
      diverse long QT mutations.
AB  - About 300 loss-of-function mutations in the IKs channel have been identified in
      patients with Long QT syndrome and cardiac arrhythmia. How specific mutations
      cause arrhythmia is largely unknown and there are no approved IKs channel
      activators for treatment of these arrhythmias. We find that several Long QT
      syndrome-associated IKs channel mutations shift channel voltage dependence and
      accelerate channel closing. Voltage-clamp fluorometry experiments and kinetic
      modeling suggest that similar mutation-induced alterations in IKs channel
      currents may be caused by different molecular mechanisms. Finally, we find that
      the fatty acid analogue N-arachidonoyl taurine restores channel gating of many
      different mutant channels, even though the mutations are in different domains of
      the IKs channel and affect the channel by different molecular mechanisms. N
      arachidonoyl taurine is therefore an interesting prototype compound that may
      inspire development of future IKs channel activators to treat Long QT syndrome
      caused by diverse IKs channel mutations.

PMID- 27690228
TI  - Impairment of Biofilm Formation by TiO2 Photocatalysis through Quorum Quenching.
AB  - The release of nanomaterials into the environment, due to their massive
      production and application today, has caused ecological and health safety
      concerns. Semiconductor photocatalysts like TiO2 exhibit cytotoxicity to
      bacterial cells when exposed to UV irradiation. However, information about their
      impacts on individual or group bacterial behaviors is limited. In this work, the
      biofilm formation of Escherichia coli K12 in the presence of TiO2 with and
      without UV irradiation was investigated and biofilm formation was found not to be
      affected under the sole application of TiO2 or UV irradiation. However, biofilm
      development was substantially delayed by TiO2 under UV irradiation, although no
      obvious cytotoxicity to cell growth was observed. The reactive oxygen species
      photogenerated by TiO2 were found to quench the autoinducer 2 (AI-2) signals
      secreted by E. coli K12. As a result, the initiation of quorum sensing for
      biofilm formation activated by AI-2 was restrained. The expressions of two
      biofilm-formation-related genes, motA and rcsB, were also suppressed. A dose of
      an AI-2 precursor, 4,5-dihydroxy-2,3-pentanedione, effectively restored the
      biofilm development. These results show that the photoexcited TiO2 could suppress
      biofilm formation through quenching AI-2 signals. This work may facilitate a
      better understanding about the ecological effects of increasingly released
      nanomaterials and provide implications for development of antifouling membranes.

PMID- 27690229
TI  - The Utilization of Rehabilitation in Patients with Hemophilia A in Taiwan: A
      Nationwide Population-Based Study.
AB  - INTRODUCTION: Rehabilitation plays an important role in the physical health of
      patients with hemophilia. However, comprehensive information regarding the
      utilization of rehabilitation for such patients remains scarce. AIM: This
      population-based study aimed to examine the characteristics, trends, and most
      important factors affecting rehabilitation usage in patients with hemophilia A
      using a nationwide database in Taiwan. METHODS: Data from 777 patients with
      hemophilia A who were registered in the National Health Insurance Research
      Database between 1998 and 2008 were analyzed using SAS 9.0. RESULTS:
      Musculoskeletal or nervous system-related surgical procedures and clotting factor
      VIII concentrate costs were identified as factors affecting rehabilitation usage;
      musculoskeletal or nervous system-related surgical procedures (odds ratio =
      3.788; P < 0.001) were the most important predictor of whether a patient with
      hemophilia A would use rehabilitation services. Joint disorders, arthropathies,
      bone and cartilage disorders, intracranial hemorrhage, and brain trauma were
      common diagnoses during rehabilitation use. The costs of physical therapy
      (physiotherapy) comprised the majority (71.2%) of rehabilitation therapy
      categories. Increasingly, rehabilitation therapy was performed at physician
      clinics. The total rehabilitation costs were <0.1% of the total annual medical
      costs. CONCLUSION: Musculoskeletal or nervous system-related surgical procedures
      and increased use of clotting factor VIII concentrate affect the rehabilitation
      utilization of patients with hemophilia A the most. The findings in this study
      could help clinicians comprehensively understand the rehabilitation utilization
      of patients with hemophilia A.

PMID- 27690230
TI  - Turnover of 137Cs in 'soil-tree' system: An experience of measuring the isotope
      flows in a Siberian conifer forest.
AB  - Little attention has been paid to the uptake of 137Cs in natural forests under
      low levels of the isotope fallout when no immediate ecological danger presents.
      Here we present the extended assessments of the soil-to-plant and canopy-to
      litter flows of 137Cs recently evaluated in a native Siberian forested area. The
      area undergoes a typical after-fire long term succession, with light-conifer
      upper story being followed by undergrowth of Siberian fir and other dark-conifer
      species. The one-year-old needles of Siberian fir were found to accumulate the
      largest concentration of the isotope, 4.10 Bq/kg oven-dry weight during the first
      growth season, as compared with older needles that accumulated 4.67 Bq/kg oven
      dry weight in 2-3 years of growth. Based on these data an approach was developed
      that, hypothetically, can allow one to estimate the 137Cs activity concentration
      in soil solutions. Direct activity measurements in the soil solutions were not
      possible. The isotope activity in soil solutions was estimated to be 0.0061
      0.0105 Bq/L. Based on the original data from the litter fall the annual flow of
      the isotope from the upper canopy to on-ground litter was found to be 0.42-0.84
      Bq/m2. The amount of 137Cs that returns yearly back from canopy with falling
      litter was estimated to be 0.012-0.015% of the total soil isotope content. A
      combination of the estimations obtained in our study with the values of global
      137Cs fallout allowed us to assess the ages (the time of formation) of horizons
      of the soils in the area.

PMID- 27690231
TI  - Genome Sequence Variability Predicts Drug Precautions and Withdrawals from the
      Market.
AB  - Despite substantial premarket efforts, a significant portion of approved drugs
      has been withdrawn from the market for safety reasons. The deleterious impact of
      nonsynonymous substitutions predicted by the SIFT algorithm on structure and
      function of drug-related proteins was evaluated for 2504 personal genomes. Both
      withdrawn (n = 154) and precautionary (Beers criteria (n = 90), and US FDA
      pharmacogenomic biomarkers (n = 96)) drugs showed significantly lower genomic
      deleteriousness scores (P < 0.001) compared to others (n = 752). Furthermore, the
      rates of drug withdrawals and precautions correlated significantly with the
      deleteriousness scores of the drugs (P < 0.01); this trend was confirmed for all
      drugs included in the withdrawal and precaution lists by the United Nations,
      European Medicines Agency, DrugBank, Beers criteria, and US FDA. Our findings
      suggest that the person-to-person genome sequence variability is a strong
      independent predictor of drug withdrawals and precautions. We propose novel
      measures of drug safety based on personal genome sequence analysis.

PMID- 27690232
TI  - Patient-Reported Vision-Related Quality-of-Life Differences between Primary Angle
      Closure Glaucoma and Primary Open-Angle Glaucoma.
AB  - PURPOSE: To investigate the different impacts on patient-reported vision-related
      quality of life (pVRQOL) outcomes in patients with primary angle-closure
      glaucoma(PACG) and primary open-angle glaucoma(POAG). METHODS: Prospective cross
      sectional study. PACG and POAG patients who had a best-corrected visual
      acuity(BCVA) in the better eye equal to or better than 20/60, intraocular
      pressure controlled at or below 25 mmHg and reliable visual field test were
      invited to participate. The control group included patients with BCVA in the
      better eye equal to or better than 20/60 and who did not have major eye disease.
      A validated Taiwanese version of the 25-item National Eye Institute Visual
      Function Questionnaire (NEI VFQ-25(T)) was performed to assess pVRQOL. The
      association between each domain of NEI VFQ-25(T) among 3 groups was determined
      using multivariable linear regression analysis. RESULTS: A total of 106 PACG, 186
      POAG, and 95 controls were enrolled. In multivariable regression analysis of all
      three groups(PACG/POAG/controls), compared to POAG, PACG showed a weakly positive
      association with social functioning (R2 = 0.13, beta = 0.22, P = 0.04). PACG
      showed no significantly negative impact on pVRQOL compared to controls. Taking
      only glaucoma patients into consideration, PACG patients had a higher score on
      social functioning compared to POAG (R2 = 0.16, beta = 0.27, P = 0.01). The
      results of other domains of NEI VFQ-25(T) between the two groups did not differ
      significantly(p>0.05). CONCLUSIONS: In patients with controlled disease, the
      impact of PACG and POAG on most domains of NEI VFQ-25(T) were similar, except for
      better social functioning in PACG compared to POAG.

PMID- 27690233
TI  - Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic
      Alterations in Mouse Germ Cells.
AB  - Dexrazoxane has been approved to treat anthracycline-induced cardiomyopathy and
      extravasation. However, the effect of dexrazoxane on epirubicin-induced genetic
      alterations in germ cells has not yet been reported. Thus, the aim of this study
      was to determine whether dexrazoxane modulates epirubicin-induced genetic damage
      in the germ cells of male mice. Our results show that dexrazoxane was not
      genotoxic at the tested doses. Furthermore, it protected mouse germ cells against
      epirubicin-induced genetic alterations as detected by the reduction in disomic
      and diploid sperm, spermatogonial chromosomal aberrations, and abnormal sperm
      heads. The attenuating effect of dexrazoxane was greater at higher dose,
      indicating a dose-dependent effect. Moreover, sperm motility and count were
      ameliorated by dexrazoxane pretreatment. Epirubicin induced marked biochemical
      changes characteristic of oxidative DNA damage including elevated 8-hydroxy-2'
      deoxyguanosine levels and reduction in reduced glutathione. Pretreatment of mice
      with dexrazoxane before epirubicin challenge restored these altered endpoints. We
      conclude that dexrazoxane may efficiently mitigate the epirubicin insult in male
      germ cells, and prevent the enhanced risk of abnormal reproductive outcomes and
      associated health risks. Thus, pretreating patients with dexrazoxane prior to
      epirubicin may efficiently preserve not only sperm quality but also prevent the
      transmission of genetic damage to future generations.

PMID- 27690234
TI  - Selective internal radiation therapy for liver metastases from colorectal cancer.
AB  - Liver metastases are often the dominant site of metastatic disease in colorectal
      cancer. Selective internal radiation therapy (SIRT) involves embolising
      radiolabeled spheres (SIR-Spheres) into the arterial supply of the liver. This
      review assesses the effectiveness and toxicity of SIRT in the treatment of
      metastatic colorectal cancer liver metastasis when given alone or with systemic
      or regional hepatic artery chemotherapy. We reviewed only randomised controlled
      trials comparing SIRT and chemotherapy (systemic and/or regional) with
      chemotherapy alone, or comparing SIRT alone with best supportive care. Only four
      randomized trials were identified. Due to heterogeneity of the patients and
      treatments received it was not possible to perform a formal meta-analysis,
      therefore this is a descriptive analysis only. All studies included patients with
      either liver only or liver dominant metastatic colorectal cancer. Two trials
      compared SIRT alone and SIRT with chemotherapy first line. The first with only 21
      patients revealed a significant improvement in PFS and median survival with SIRT.
      The larger second study SIRFLOX of 530 patients comparing SIRT and current
      standard first line FOLFOX chemotherapy (+/- bevacizumab) with standard FOLFOX+/
      bevacizumab alone. There was no improvement in overall PFS with addition of SIRT.
      In chemotherapy refractory patients SIRT and systemic chemotherapy (fluorouracil)
      improved progression free survival but not overall survival. A final study (63
      patients) compared SIRT and regional chemotherapy (floxuridine) with regional
      chemotherapy alone in first line showed no significant difference in progression
      free survival and median survival. There remains a lack of evidence that SIRT
      improves survival or quality of life in patients with metastatic colorectal
      cancer. The overall survival results from SIRFLOX combined with FOXFIRE and
      FOXFIRE Global are awaited.

PMID- 27690236
TI  - Specific directions of ultrasound propagation in double potassium tungstates for
      light modulation.
AB  - Acousto-optical characteristics of double potassium tungstates are analyzed and
      specific directions for light modulation are found. First, an important subgroup
      of elasto-optic coefficients of KYb(WO4)2 and KLu(WO4)2 crystals are calculated
      with use of experimental data. It is revealed that with proper choice of
      ultrasound direction the acousto-optical figure-of-merit approximately 2 times
      exceeds the maximum value detected in previous experiments. Another unique
      direction is determined, which permits modulation of randomly polarized light.
      The elasto-optic characteristics of KYb(WO4)2 and KLu(WO4)2 crystals are compared
      to those of previously investigated materials of the same crystal group:
      KY(WO4)2, KGd(WO4)2.

PMID- 27690235
TI  - Dnmt3a Is a Haploinsufficient Tumor Suppressor in CD8+ Peripheral T Cell
      Lymphoma.
AB  - DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that
      is frequently mutated in human hematologic malignancies. We have previously shown
      that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic
      leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+
      mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both
      diseases. 10% of Dnmt3a+/- mice develop lymphomas, suggesting that Dnmt3a is a
      haploinsufficient tumor suppressor in PTCL. DNA methylation was deregulated
      genome-wide with 10-fold more hypo- than hypermethylated promoters and enhancers,
      demonstrating that hypomethylation is a major event in the development of PTCL.
      Hypomethylated promoters were enriched for binding sites of transcription factors
      AML1, NF-kappaB and OCT1, implying the transcription factors potential
      involvement in Dnmt3a-associated methylation. Whereas 71 hypomethylated genes
      showed an increased expression in PTCL, only 3 hypermethylated genes were
      silenced, suggesting that cancer-specific hypomethylation has broader effects on
      the transcriptome of cancer cells than hypermethylation. Interestingly,
      transcriptomes of Dnmt3a+/- and Dnmt3aDelta/Delta lymphomas were largely
      conserved and significantly overlapped with those of human tumors. Importantly,
      we observed downregulation of tumor suppressor p53 in Dnmt3a+/- and
      Dnmt3aDelta/Delta lymphomas as well as in pre-tumor thymocytes from 9 months old
      but not 6 weeks old Dnmt3a+/- tumor-free mice, suggesting that p53 downregulation
      is chronologically an intermediate event in tumorigenesis. Decrease in p53 is
      likely an important event in tumorigenesis because its overexpression inhibited
      proliferation in mouse PTCL cell lines, suggesting that low levels of p53 are
      important for tumor maintenance. Altogether, our data link the haploinsufficient
      tumor suppressor function of Dnmt3a in the prevention of mouse mature CD8+ PTCL
      indirectly to a bona fide tumor suppressor of T cell malignancies p53.

PMID- 27690237
TI  - Acoustical spinner tweezers with nonparaxial Hermite-Gaussian acoustical-sheets
      and particle dynamics.
AB  - Hermite-Gaussian (HGl) acoustical-sheets are introduced and their beamforming
      properties are examined. A general nonparaxial mathematical solution for the
      incident beam of any order l is derived based on the angular spectrum
      decomposition in plane waves. The beam-shape coefficients characterizing the
      incident beam in cylindrical coordinates are expressed in an integral form and
      computed using the standard numerical integration procedure based on the
      trapezoidal rule. The analysis is further extended to calculate the longitudinal
      and transverse acoustic radiation force functions as well as the axial radiation
      torque function for a viscous fluid cylindrical cross-section submerged in a non
      viscous fluid and located arbitrarily in space in the field of the HGl beams in
      the Rayleigh and resonance (Mie) regimes. The numerical results show that the
      absorptive cylinder can be pulled, pushed, or manipulated and rotated around its
      center of mass when placed in the acoustical field of a HGl beam. Clockwise or
      anticlockwise rotations can arise depending on the cylinder position in the
      acoustic field. Moreover, a particle dynamics analysis is established based on
      Newton's second law of motion during which the trajectories of the cylinder
      subjected to the acoustical field of forces are computed. The results can find
      potential applications in particle manipulation and handling, acoustical
      microscopy imaging, and surface acoustic waves to name a few examples.

PMID- 27690239
TI  - Synthesis and characterization of biocompatible antimicrobial N-halamine
      functionalized titanium dioxide core-shell nanoparticles.
AB  - As one of the most powerful biocides, N-halamine based antimicrobial materials
      have attracted much interest due to their non-toxicity, rechargeability, and
      rapid inactivation against a broad range of microorganisms. In this study, novel
      titanium dioxide-ADMH core-shell nanoparticles [TiO2@poly (ADMH-co-MMA) NPs] were
      prepared via miniemulsion polymerization using 3-allyl-5,5-dimethylhydantoin
      (ADMH) and methyl methacrylate (MMA) with nano-TiO2. The produced nanoparticles
      were characterized by FT-IR, TEM, TGA, and XPS. The UV stability of N-halamine
      nanoparticles has been improved with the addition of titanium dioxide. After
      chlorination treatment by sodium hypochlorite, biocidal efficacies of the
      chlorinated nanoparticles against S. aureus (ATCC 6538) and E. coli O157:H7 (ATCC
      43895) were determined. The nanoparticles showed excellent antimicrobial
      properties against bacteria within brief contact time. In addition, in vitro cell
      cytocompatibility tests showed that the antibacterial nanoparticles had good
      biocompatibility.

PMID- 27690238
TI  - CXCL1-Mediated Interaction of Cancer Cells with Tumor-Associated Macrophages and
      Cancer-Associated Fibroblasts Promotes Tumor Progression in Human Bladder Cancer.
AB  - Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are
      reported to be associated with poor prognosis, depending on their pro-tumoral
      roles. Current knowledge of TAMs and CAFs in the tumor microenvironment of
      urothelial cancer of the bladder (UCB) is limited. Therefore, we investigated the
      paracrine effect induced by TAMs and CAFs in the tumor microenvironment of human
      UCB. For this, we first carried out immunohistochemical analysis for CXCL1, CD204
      (TAM marker), alphaSMA (CAF marker), E-cadherin, and MMP2 using 155 UBC tissue
      samples. Next, CXCL1-overexpressing clones of THP-1-derived TAMs and NIH3T3
      derived CAFs were developed by lentiviral vector infection. The
      immunohistochemical study showed high CXCL1 levels in UCB cells to be associated
      with enhanced recruitment of TAMs/CAFs, higher metastatic potential, and poor
      prognosis. Three-dimensional (3D) co-culture of UCB cells and TAMs/CAFs suggested
      that CXCL1 production in TAMs/CAFs play an important role in cell-to-cell
      adhesion and interaction among cancer cells and these stromal cells. CXCL1
      expressing TAMs/CAFs enhanced tumor growth of subcutaneous UCB tumors in nude
      mice when injected together. In addition, an experiment using the orthotopic
      bladder cancer model revealed that CXCL1 production in TAMs/CAFs supported tumor
      implantation into the murine bladder wall and UCB growth when injected together,
      which was confirmed by clinical data of patients with bladder cancer. Thus, CXCL1
      signaling in the tumor microenvironment is highly responsible for repeated
      intravesical recurrence, disease progression, and drug resistance through
      enhanced invasion ability. In conclusion, disrupting CXCL1 signaling to
      dysregulate this chemokine is a promising therapeutic approach for human UCB.

PMID- 27690241
TI  - In vitro drug release and percutaneous behavior of poloxamer-based hydrogel
      formulation containing traditional Chinese medicine.
AB  - For the treatment of atopic dermatitis (AD), we have developed a transdermal
      functionalized textile therapy based on thermosensitive poloxamer 407 (P407)
      hydrogel containing a traditional Chinese herbal medicine. This study aims to
      investigate the effects of various formulation variables of P407/carboxymethyl
      cellulose sodium (P407/CMCs) composite hydrogel on the release of Cortex Moutan
      (CM) extract. Concentrations of P407 and CMCs showed significant influence on the
      release due to alteration of bulk viscosity of the system. An increase in pH
      values of release medium was found to appreciably impede the release of polar
      drug (CM) due to ionization. Elevated temperatures were also shown to facilitate
      the drug release. Moreover, the diffusional release behavior of CM from P407/CMCs
      composite hydrogel was found to follow the first-order kinetic model.
      Additionally, transdermal studies showed that permeability of the drug through
      the skin can be enhanced with addition of CMCs in the hydrogel formulation.

PMID- 27690240
TI  - Redox responsive liposomal nanohybrid cerasomes for intracellular drug delivery.
AB  - Cerasome is a freshly developped bilayer vehicle that resemble traditional
      liposome but has higher mophorlogical stability. In this study, a novel redox
      responsive cerasome (RRC) was developed for tumor-targeting drug delivery. The
      cerasome-forming lipid (CFL) that comprise a cleavable disulfide bond as
      connector unit of the triethoxysilyl head and the hydrophobic alkyl double chain
      was synthesized and subsequently used to prepare cerasome through ethanol
      injection method. RRC that has liposome-resembling lipid bilayer structure was
      proved being outstanding at drug loading capacity as well as morphological
      stability as compared to conventional liposomes. In addition, in vitro drug
      release tests of DOX/RRCs showed a redox-responsive drug release profile:
      accelerated DOX releasing compared to reduction-insensitive cerasomes (RICs) in
      the presence of 10mM of GSH. Under the same condition, the reduction sensibility
      of RRC was further proved by increased hydrodynamic diameter and destroying of
      integrity from DLS and SEM results. RRC showed non-toxic to human embryonic
      kidney 293 cells, indicating that this material has good biocompatibility. On the
      other hand, DOX/RRCs showed a resemble IC50 (half inhibitory concentration) value
      to that of free DOX to human hepatoma SMMC-7721 cells and breast cancer MCF-7
      cells. IC50 values at 48h were found to decrease in the following order:
      DOX/RIC>DOX/RRC>DOX. Taken together, the RRC developped in this study is of great
      potential to be utilized as a promising platform for intracellular anticancer
      drug delivery.

PMID- 27690242
TI  - Biomimetic HDL nanoparticle mediated tumor targeted delivery of indocyanine green
      for enhanced photodynamic therapy.
AB  - Photodynamic therapy has emerged as a promising strategy for cancer treatment. To
      ensure the efficient delivery of a photosensitizer to tumor for anticancer
      effect, a safe and tumor-specific delivery system is highly desirable. Herein, we
      introduce a novel biomimetic nanoparticle named rHDL/ICG (rHDL/I), by loading
      amphiphilic near-infrared (NIR) fluorescent dye indocyanine green (ICG) into
      reconstituted high density lipoproteins (rHDL). In this system, rHDL can mediate
      photoprotection effect and receptor-guided tumor-targeting transportation of
      cargos into cells. Upon NIR irradiation, ICG can generate fluorescent imaging
      signals for diagnosis and monitoring therapeutic activity, and produce singlet
      oxygen to trigger photodynamic therapy (PDT). Our studies demonstrated that
      rHDL/I exhibited excellent size and fluorescence stability, light-triggered
      controlled release feature, and neglectable hemolytic activity. It also showed
      equivalent NIR response compared to free ICG under laser irradiation.
      Importantly, the fluorescent signal of ICG loaded in rHDL/I could be visualized
      subcellularly in vitro and exhibited metabolic distribution in vivo, presenting
      superior tumor targeting and internalization. This NIR-triggered image-guided
      nanoparticle produced outstanding therapeutic outcomes against cancer cells,
      demonstrating great potential of biomimetic delivery vehicles in future clinical
      practice.

PMID- 27690243
TI  - Zeta-potential data reliability of gold nanoparticle biomolecular conjugates and
      its application in sensitive quantification of surface absorbed protein.
AB  - Zeta potentials (ZP) of gold nanoparticle bioconjugates (AuNP-bios) provide
      important information on surface charge that is critical for many applications
      including drug delivery, biosensing, and cell imaging. The ZP measurements (ZPMs)
      are conducted under an alternative electrical field at a high frequency under
      laser irradiation, which may strongly affect the status of surface coating of
      AuNP-bios and generate unreliable data. In this study, we systemically evaluated
      the ZP data reliability (ZPDR) of citrate-, thiolated single stranded DNA-, and
      protein-coated AuNPs mainly according to the consistence of ZPs in the repeated
      ZPMs and the changes of the hydrodynamic size before and after the ZPMs. We found
      that the ZPDR was highly dependent on both buffer conditions and surface
      modifications. Overall, the higher ionic strength of the buffer and the lower
      affinity of surface bounders were related with the worse ZPDR. The ZPDR of
      citrate-coated AuNP was good in water, but bad in 10mM phosphate buffer (PB),
      showing substantially decrease of the absolute ZP values after each measurement,
      probably due to the electrical field facilitated adsorption of negatively charged
      phosphate ions on AuNPs. The significant desorption of DNAs from AuNP was
      observed in the PB containing medium concentration of NaCl, but not in PB. The
      excellent ZPDR of bovine serum albumin (BSA)-coated AuNP was observed at high
      salt concentrations and low surface coverage, enabling ZPM as an ultra-sensitive
      tool for protein quantification on the surface of AuNPs with a single molecule
      resolution.

PMID- 27690244
TI  - Surface chemistry from wettability and charge for the control of mesenchymal stem
      cell fate through self-assembled monolayers.
AB  - Self-assembled monolayers (SAMs) of alkanethiols on gold are highly controllable
      model substrates and have been employed to mimic the extracellular matrix for
      cell-related studies. This study aims to systematically explore how surface
      chemistry influences the adhesion, morphology, proliferation and osteogenic
      differentiation of mouse mesenchymal stem cells (mMSCs) using various functional
      groups (-OEG, -CH3, -PO3H2, -OH, -NH2 and -COOH). Surface analysis demonstrated
      that these functional groups produced a wide range of wettability and charge: 
      OEG (hydrophilic and moderate iso-electric point (IEP)), -CH3 (strongly
      hydrophobic and low IEP), -PO3H2 (moderate wettability and low IEP), -OH
      (hydrophilic and moderate IEP), -NH2 (moderate wettability and high IEP) and 
      COOH (hydrophilic and low IEP). In terms of cell responses, the effect of
      wettability may be more influential than charge for these groups. Moreover,
      compared to -OEG and -CH3 groups, -PO3H2, -OH, -NH2 and -COOH functionalities
      tended to promote not only cell adhesion, proliferation and osteogenic
      differentiation but also the expression of alphav and beta1 integrins. This
      finding indicates that the surface chemistry may guide mMSC activities through
      alphav and beta1 integrin signaling pathways. Model surfaces with controllable
      chemistry may provide insight into biological responses to substrate surfaces
      that would be useful for the design of biomaterial surfaces.

PMID- 27690246
TI  - The use of team-based learning in a second year undergraduate pre-registration
      nursing course on evidence-informed decision making.
AB  - More engaging teaching and learning strategies are needed to teach research
      related courses to pre-registration nursing students. Team-based learning was
      implemented within a second year pre-registration nursing evidence-informed
      decision making course. Results from a questionnaire survey indicated that 70%
      believed team-based learning was appropriate for the course, 60% that it was an
      effective and motivating learning strategy, and 54% recommended using team-based
      learning in other courses. The results from ten student interviews illustrated
      the positive way in which team-based learning was perceived, and how the students
      thought it contributed to their learning. Test results were improved with an
      increase in the numbers of students achieving 70% or higher; and higher scores
      for students in the lowest quartile. Team-based learning was shown to be an
      effective strategy that preserved the benefits of small group teaching with large
      student groups.

PMID- 27690245
TI  - Biocompatible electrically conductive nanofibers from inorganic-organic shape
      memory polymers.
AB  - A porous shape memory scaffold with both biomimetic structures and electrical
      conductivity properties is highly promising for nerve tissue engineering
      applications. In this study, a new shape memory polyurethane polymer which
      consists of inorganic polydimethylsiloxane (PDMS) segments with organic
      poly(epsilon-caprolactone) (PCL) segments was synthesized. Based on this
      poly(PCL/PDMS urethane), a series of electrically conductive nanofibers were
      electrospun by incorporating different amounts of carbon-black. Our results
      showed that after adding carbon black into nanofibers, the fiber diameters
      increased from 399+/-76 to 619+/-138nm, the crystallinity decreased from 33 to
      25% and the resistivity reduced from 3.6 GOmega/mm to 1.8 kOmega/mm. Carbon black
      did not significantly influence the shape memory properties of the resulting
      nanofibers, and all the composite nanofibers exhibited decent shape recovery
      ratios of >90% and shape fixity ratios of >82% even after 5 thermo-mechanical
      cycles. PC12 cells were cultured on the shape memory nanofibers and the composite
      scaffolds showed good biocompatibility by promoting cell-cell interactions. Our
      study demonstrated that the poly(PCL/PDMS urethane)/carbon-black nanofibers with
      shape memory properties could be potentially used as smart 4-dimensional (4D)
      scaffolds for nerve tissue regeneration.

PMID- 27690248
TI  - Confocal Luminescence Lifetime Imaging with Variable Scan Velocity and Its
      Application to Oxygen Sensing.
AB  - The dependence of the luminescence lifetime on the probe environment is the basis
      of a range of sensing techniques. The major advantage of using the lifetime as
      the sensitive parameter is its independence on the probe concentration. However,
      the instrumentation for lifetime measurements is complex, generally requiring
      time-resolved excitation and detection. Here, we present a simple method for the
      measurement of luminescence lifetimes on the microsecond scale based on variable
      excitation time determined by the scanning velocity. The technique is implemented
      in a confocal laser scanning microscope (CLSM), thus allowing not only simple
      lifetime measurement but also phosphorescence lifetime imaging. Since the method
      exploits the spatiotemporal dependence of sample excitation in a CLSM, there is
      no need for a pulsed or modulated light source or for additional time-resolved
      detection. The method can be realized in a standard CLSM without any
      modifications. The principle is demonstrated on oxygen sensing by collisional
      quenching of an oxygen-sensitive ruthenium(II) complex.

PMID- 27690249
TI  - Chiral Phosphoric Acid Catalyzed Asymmetric Oxidative Dearomatization of
      Naphthols with Quinones.
AB  - A highly enantioselective oxidative dearomatization of naphthols with quinones
      catalyzed by a chiral spirocyclic phosphoric acid is described. The strategy
      provides concise access to enantioenriched cyclohexadienones with a quinone
      moiety. Remarkably, the obtained products could be easily transformed to a
      potentially useful dihydronaphtho[2,1-b]benzofuran scaffold.

PMID- 27690247
TI  - Mathematical Modeling of the Transmission Dynamics of Clostridium difficile
      Infection and Colonization in Healthcare Settings: A Systematic Review.
AB  - BACKGROUND: We conducted a systematic review of mathematical models of
      transmission dynamic of Clostridium difficile infection (CDI) in healthcare
      settings, to provide an overview of existing models and their assessment of
      different CDI control strategies. METHODS: We searched MEDLINE, EMBASE and Web of
      Science up to February 3, 2016 for transmission-dynamic models of Clostridium
      difficile in healthcare settings. The models were compared based on their natural
      history representation of Clostridium difficile, which could include health
      states (S-E-A-I-R-D: Susceptible-Exposed-Asymptomatic-Infectious-Resistant
      Deceased) and the possibility to include healthcare workers and visitors (vectors
      of transmission). Effectiveness of interventions was compared using the relative
      reduction (compared to no intervention or current practice) in outcomes such as
      incidence of colonization, CDI, CDI recurrence, CDI mortality, and length of
      stay. RESULTS: Nine studies describing six different models met the inclusion
      criteria. Over time, the models have generally increased in complexity in terms
      of natural history and transmission dynamics and number/complexity of
      interventions/bundles of interventions examined. The models were categorized into
      four groups with respect to their natural history representation: S-A-I-R, S-E-A
      I, S-A-I, and S-E-A-I-R-D. Seven studies examined the impact of CDI control
      strategies. Interventions aimed at controlling the transmission, lowering CDI
      vulnerability and reducing the risk of recurrence/mortality were predicted to
      reduce CDI incidence by 3-49%, 5-43% and 5-29%, respectively. Bundles of
      interventions were predicted to reduce CDI incidence by 14-84%. CONCLUSIONS:
      Although CDI is a major public health problem, there are very few published
      transmission-dynamic models of Clostridium difficile. Published models vary
      substantially in the interventions examined, the outcome measures used and the
      representation of the natural history of Clostridium difficile, which make it
      difficult to synthesize results and provide a clear picture of optimal
      intervention strategies. Future modeling efforts should pay specific attention to
      calibration, structural uncertainties, and transparent reporting practices.

PMID- 27690250
TI  - Validity of the Stokes-Einstein relation in liquids: simple rules from the excess
      entropy.
AB  - It is becoming common practice to consider that the Stokes-Einstein relation D/T~
      eta -1 usually works for liquids above their melting temperatures although there
      is also experimental evidence for its failure. Here we investigate numerically
      this commonly-invoked assumption for simple liquid metals as well as for their
      liquid alloys. Using ab initio molecular dynamics simulations we show how entropy
      scaling relationships developed by Rosenfeld can be used to predict the
      conditions for the validity of the Stokes-Einstein relation in the liquid phase.
      Specifically, we demonstrate the Stokes-Einstein relation may break down in the
      liquid phase of some liquid alloys mainly due to the presence of local structural
      ordering as evidenced in their partial two-body excess entropies. Our findings
      shed new light on the understanding of transport properties of liquid materials
      and will trigger more experimental and theoretical studies since excess entropy
      and its two-body approximation are readily obtainable from standard experiments
      and simulations.

PMID- 27690251
TI  - Subependymal giant cell astrocytoma in a genetically negative tuberous sclerosis
      complex adult: Case report.
AB  - INTRODUCTION: The well-described entity of Subependymal Giant Cell Astrocytoma
      (SEGA) in the setting of Tuberous Sclerosis Complex (TSC) is profound in current
      literature. It has been described in children as well as adults with or without
      identifiable clinical presentations of tuberous sclerosis. To our knowledge there
      has not been any report of a negative genetic workup of Tuberous Sclerosis
      Complex in an adult patient presenting with an isolated SEGA. CASE REPORT: We
      present a case of a 25-year-old female with no medical history who presented to
      the emergency room for headaches. Further workup included gadolinium enhanced MRI
      of the brain which revealed a homogenously enhancing mass in the left lateral
      ventricle with eccentric calcification and resultant obstructive hydrocephalus. A
      left frontal craniotomy with an interhemispheric transcallosal approach was taken
      for complete removal of the mass. DISCUSSION: Final pathological diagnosis was
      SEGA with suggestive cell population, positive GFAP and positive synaptophysin.
      Genetic testing included TSC1 (MLPA, DNA Sequencing) and TSC2 (MLPA, DNA
      Sequencing), which were all negative. The panel did not identify mutations
      associated with Tuberous Sclerosis. CONCLUSION: Rare cases of isolated SEGA have
      been reported in patients who do not have typical features of tuberous sclerosis,
      and may represent minimal penetrance of the disease with an attenuated phenotype.
      Negative genetic testing, as demonstrated, can be seen in adults with isolated
      SEGA. With a negative genetic workup of TSC, regular follow up may still be
      necessary; however this may prove to be low yield for identifying any TSC
      features in the future.

PMID- 27690252
TI  - Octreotide: The IIH therapy beyond weight loss, carbonic anhydrase inhibitors,
      lumbar punctures and surgical/interventional treatments.
AB  - OBJECTIVE: Idiopathic intracranial hypertension (IIH) is characterized by
      elevated intracranial pressure without a space-occupying cerebral lesion, venous
      sinus thrombosis or hydrocephalus and with normally composited cerebrospinal
      fluid (CSF). Main symptoms are headache, sight disturbances and potential visual
      impairment. Weight loss, carbonic anhydrase inhibitors, lumbar punctures with CSF
      drain, CSF shunting, optic nerve sheath fenestration, and venous sinus stenting
      are common IIH therapies. Octreotide, a synthetic somatostatin analogue, also
      effectively suspends IIH symptoms. Here, treatment with octreotide on five so far
      inefficiently treated IIH patients is presented and discussed. METHODS: Five
      female patients with IIH and a history of failed therapy regimes were treated
      with octreotide, to be administered everyday subcutaneously for six months with
      identified doses high enough to suspend all clinical IIH symptoms. After tapering
      for two months, the further clinical course was to be monitored. RESULTS: All
      patients were IIH symptom-free under octreotide. After tapering, one patient
      remained IIH symptom-free; one patient became IIH symptom-free under
      intramuscular octreotide after failure of former therapy regimes; one patient
      became IIH symptom-free on low-dose carbonic anhydrase inhibitors; one patient
      had an allergic reaction and paused octreotide, after successful desensitization,
      tooth ache developed, forcing octreotide tapering; one patient had another shunt
      revision alleviating IIH symptoms. CONCLUSION: We confirmed that a) clinical IIH
      symptoms are suspended during octreotide exposure; b) 6-month administration can
      sustainably abolish IIH symptoms; c) desensitization is possible for octreotide
      allergy. When IIH symptoms reoccur after limited-time octreotide administration,
      re-application of formerly ineffective carbonic anhydrase inhibitors can suspend
      IIH symptoms. Intramuscular octreotide is a promising long-term therapy option.

PMID- 27690253
TI  - One-Pot Synthesis of Chiral, Spirocyclic 4-Hydantoin-Proline Derivatives for
      Incorporation into Spiroligomer-Based Macromolecules.
AB  - Derivatives of 4-hydantoin-proline have been synthesized via a direct two-step
      alkylation method. This method is valuable in the development of applications of
      N,N'-disubstituted hydantoin bearing alpha-amino acids by improving yields,
      reducing the time and number of steps required to synthesize these substituted
      molecules, and enabling late stage functionalization of spiroligomer termini.
      Over 20 unique electrophiles have been tested, highlighting the inherent
      versatility of this chemistry.

PMID- 27690255
TI  - Aromaticity and Through-Space Interaction between Aromatic Rings in
      [2.2]Paracyclophanes.
AB  - The HOMA index calculated for [2.2]paracyclophanes in the solid state reveals a
      slight decrease of aromaticity. Interactions between aromatic rings of
      [2.2]paracyclophane have been investigated using AIM and NCI analysis in both
      crystal and optimized [2.2]paracyclophane structures. AIM analysis showed that
      the C...C bond path between the two aromatic rings is present only in few
      [2.2]paracyclophanes. The NCI approach visualized the dispersion and repulsive
      interactions between the aromatic rings of every [2.2]paracyclophane. Combination
      of AIM and the NCI approach is necessary for determining and identifying
      nonbonded interactions in [2.2]paracyclophanes.

PMID- 27690254
TI  - Aldgamycins J-O, 16-Membered Macrolides with a Branched Octose Unit from
      Streptomycetes sp. and Their Antibacterial Activities.
AB  - Six new 16-membered macrolides with a rare branched octose unit, aldgamycins J-O
      (1-6), along with two known compounds, swalpamycin B (7) and chalcomycin (8),
      were isolated from Streptomyces sp. HK-2006-1. Their structures were determined
      by detailed spectroscopic and X-ray crystallographic analysis. Natural products
      containing branched sugar units are rare. Aldgaropyranose and decarboxylated
      aldgaropyranose are branched octoses, specifically aldgarose-type branched
      octose. Until now, only 11 compounds have been reported to contain an aldgarose
      type branched octose. The discovery of aldgamycins J-O (1-6) adds new members of
      this type of natural product. All the compounds (1-8) herein were tested for
      antimicrobial activities against Gram-positive Staphylococcus aureus 209P, Gram
      negative Escherichia coli ATCC0111, and two fungi, Candida albicans FIM709 and
      Aspergillus niger R330. Most of these compounds showed antibacterial activity
      against S. aureus. Their preliminary structure-activity relationships are
      proposed.

PMID- 27690256
TI  - PM2.5 Exposure and Intrauterine Inflammation: A Possible Mechanism for Preterm
      and Underweight Birth.

PMID- 27690257
TI  - Hb Midnapore [beta53(D4)Ala->Val; HBB: c.161C>T]: A Novel Hemoglobin Variant with
      a Structural Abnormality Associated with IVS-I-5 (G>C) (HBB: c.92+5G>C) Found in
      a Bengali Indian Family.
AB  - We describe a novel C>T substitution at codon 53 of the HBB gene (HBB: c.161C>T).
      The proband was a transfusion-dependent beta-thalassemia major (beta-TM) patient.
      DNA was extracted and subsequently, DNA sequencing was done to detect the
      mutations on the HBB gene. Capillary zone electrophoresis (CZE) revealed the
      presence of an unknown peak. She inherited this mutation from her grandmother
      through her mother. This mutation exists in cis with the common beta0 mutation
      IVS-I-5 (G>C) (HBB: c.92+5G>C). The proband is homozygous for HBB: c.92+5G>C and
      needs monthly transfusions. On the other hand, her grandmother, mother and sister
      all possess this novel mutation cis with the heterozygous HBB: c.92+5G>C. They
      are carriers not thalassemic. This mutation produces the substitution
      beta53(D4)Ala->Val; HBB: c.161C>T, a new structural hemoglobin (Hb) variant. As
      this variant was identified in a Bengali family from Paschim Midnapore district
      of West Bengal, India, it has been designated as Hb Midnapore. This variant has
      now been reported to the HbVar database.

PMID- 27690259
TI  - Spaces and Places in the Lives of Urban Adolescents at Risk for Substance Misuse.

PMID- 27690260
TI  - Hope and Mental Health Nursing.

PMID- 27690258
TI  - Protein cage nanostructure as drug delivery system: magnifying glass on
      apoferritin.
AB  - INTRODUCTION: New frontiers in nanomedicine are moving towards the research of
      new biomaterials. Apoferritin (APO), is a uniform regular self-assemblies nano
      sized protein with excellent biocompatibility and a unique structure that affords
      it the ability to stabilize small active molecules in its inner core. Areas
      covered: APO can be loaded by applying a passive process (mainly used for ions
      and metals) or by a unique formulative approach based on disassemby/reassembly
      process. In this article, we aim to organize the experimental evidence provided
      by a number of studies on the loading, release and targeting. Attention is
      initially focused on the most investigated antineoplastic drug and contrast
      agents up to the most recent application in gene therapy. Expert opinion: Various
      preclinical studies have demonstrated that APO improved the potency and
      selectivity of some chemotherapeutics. However, in order to translate the use of
      APO into therapy, some issues must be solved, especially regarding the
      reproducibility of the loading protocol used, the optimization of nanocarrier
      characterization, detailed understanding of the final structure of loaded APO,
      and the real mechanism and timing of drug release.

PMID- 27690261
TI  - Development of Tetrachlorophthalimides as Liver X Receptor beta (LXRbeta)
      Selective Agonists.
AB  - Liver X receptor (LXR) agonists are candidates for the treatment of
      atherosclerosis via induction of ABCA1 (ATP-binding cassette A1) gene expression,
      which contributes to reverse cholesterol transport (RCT) and to cholesterol
      efflux from the liver and intestine. However, LXR agonists also induce genes
      involved in lipogenesis, such as SREBP-1c (sterol regulatory binding element
      protein 1c) and FAS (fatty acid synthase), thereby causing an undesirable
      increase in plasma and hepatic triglyceride (TG) levels. Recent studies indicate
      that LXRalpha contributes to lipogenesis in liver, and selective LXRbeta
      activation improves RCT in mice. Therefore, LXRbeta-selective agonists are
      promising candidates to improve atherosclerosis without increasing plasma or
      hepatic TG levels. However, the ligand-binding domains in the two LXR isoforms
      alpha/beta share high sequence identity, and few LXR ligands show subtype
      selectivity. In this study we identified a tetrachlorophthalimide analogue as an
      LXRbeta-selective agonist. Structural development led to (E)-4,5,6,7-tetrachloro
      2-(2-styrylphenyl)isoindoline-1,3-dione (24 a), which shows potent and selective
      LXRbeta agonistic activity in reporter gene assays. In binding assays, compound
      24 a bound to LXRbeta preferentially over LXRalpha. It also induced the
      expression of ABCA1 mRNA but not SREBP-1c mRNA in cells. Compound 24 a appears to
      be a promising lead compound for therapeutic agents to treat atherosclerosis
      without the side effects induced by LXRalpha/beta dual agonists.

PMID- 27690263
TI  - Metal Nanoparticle-Catalyzed Reduction Using Borohydride in Aqueous Media: A
      Kinetic Analysis of the Surface Reaction by Microfluidic SERS.
AB  - Hydrides are widely used in reduction reactions. In protic solvents, their
      hydrolysis generates molecular hydrogen as a second reducing agent. The
      competition between these two parallel reduction pathways has been overlooked so
      far since both typically yield the same product. We investigated the platinum
      catalyzed reduction of 4-nitrothiophenol to 4-aminothiophenol in aqueous sodium
      borohydride solution as a prominent model reaction, by using label-free SERS
      monitoring in a microfluidic reactor. Kinetic analysis revealed a strong pH
      dependence. Surprisingly, only at pH>13 the reduction is driven exclusively by
      sodium borohydride. This study demonstrates the potential of microfluidics-based
      kinetic SERS monitoring of heterogeneous catalysis in colloidal suspension.

PMID- 27690262
TI  - Detection of bone marrow changes related to estrogen withdrawal in rats with a
      tabletop stray-field NMR scanner.
AB  - PURPOSE: Osteoporosis is characterized by a decrease in bone mineral density
      (BMD). A preliminary stage of the disease is progressive bone marrow adiposity,
      caused by imbalance between osteogenesis and adipogenesis in the marrow.
      Detection of osteoporosis relies on the quantification of BMD with techniques
      such as dual-energy X-ray absorptiometry. This work aimed to detect bone marrow
      changes in an experimental model of osteopenia using a low-field tabletop NMR
      scanner. METHODS: An experiment was performed on 32 female rats, 3 months old, 16
      of which were ovariectomized (OVX) and 16 were sham-operated (sham). The femur
      and tibia from both hind limbs were isolated and underwent ex vivo NMR scans at
      four time points after the OVX and sham operations. NMR scans were complemented
      by BMD measurements and histology. RESULTS: Significant changes in the bone
      marrow of ovariectomized rats, relative to sham operated rats, were observed
      after 3.5 and 4.5 months. Bone marrow adiposity was detected by significant
      changes in T1 and T2 relaxation times, and in the diffusion coefficient.
      CONCLUSIONS: This study suggests a potential detection of changes to the bone
      marrow using a tabletop NMR device. Clinical translation may facilitate
      screening, early detection of bone weakening as a result of estrogen withdrawal,
      and monitoring of treatment efficacy. Magn Reson Med 78:860-870, 2017. (c) 2016
      International Society for Magnetic Resonance in Medicine.

PMID- 27690264
TI  - Measurement of fat content in vertebral marrow using a modified dixon sequence to
      differentiate benign from malignant processes.
AB  - PURPOSE: To determine whether fat-signal-fraction (FF) map using a modified Dixon
      sequence could help differentiate benign from malignant bone lesions. MATERIALS
      AND METHODS: Spine magnetic resonance images (MRIs) of 120 consecutive patients
      were studied by using a 3T MRI with standard T1 -weighted image (T1 WI) and
      modified-Dixon sequence for FF measurement. There were three groups: a control
      group (n = 51) with normal vertebrae; a benign group (n = 40) with focal red
      marrow deposition, Schmorl's nodes, benign compression fracture, or Modic type 1
      endplate degeneration; a malignant group (n = 29) with spinal malignancies. The
      following three parameters were measured on T1 WI and FF map by two radiologists
      independently: T1 signal intensity (SI), FF and T1 SI of normal disc (SI). Then,
      Lesion-to-disc ratio (LDR = SI of the lesion/SId ) and FF ratio of lesion and
      normal marrow were calculated. The mean values of the parameters were compared
      among the groups and Receiver Operating Characteristic (ROC) curves were
      analyzed. Then a logistic regression was performed. RESULTS: The FF (2.8%) and FF
      ratio (0.082) of malignancy were lower than benign lesions (P < 0.001). There was
      no difference in the LDR between malignancy and Schmorl's nodes (P = 0.795) or a
      benign compression fracture (P = 0.866). The areas under the ROC curves of FF and
      FF ratio were 93% and 87%, respectively, which were higher than those of the
      other parameters used for differentiation (P < 0.001). In logistic regression
      analyses, FF remained a significant variable that could be used to independently
      differentiate benign from malignant lesions, with an odds ratio of 1.9 (P <
      0.001). CONCLUSION: The FF and FF ratio obtained from FF maps using modified
      Dixon sequence could be used to distinguish between benign and malignant causes
      of focal bone marrow abnormalities when difficulty in the qualitative
      interpretation of conventional MR images arises. LEVEL OF EVIDENCE: 3 J. MAGN.
      RESON. IMAGING 2017;45:1534-1544.

PMID- 27690266
TI  - The shared and unique genetic relationship between mental well-being, depression
      and anxiety symptoms and cognitive function in healthy twins.
AB  - Alterations to cognitive function are often reported with depression and anxiety
      symptoms, yet few studies have examined the same associations with mental well
      being. This study examined the association between mental well-being, depression
      and anxiety symptoms and cognitive function in 1502 healthy adult monozygotic
      (MZ) and dizygotic (DZ) twins, and the shared/unique contribution of genetic (G)
      and environmental (E) variance. Using linear mixed models, mental well-being was
      positively associated (p < .01) with sustained attention (beta = 0.127),
      inhibition (beta = 0.096), cognitive flexibility (beta = 0.149), motor
      coordination (beta = 0.114) and working memory (beta = 0.156), whereas depression
      and anxiety symptoms were associated (p < .01) with poorer sustained attention
      (beta = -0.134), inhibition (beta = -0.139), cognitive flexibility (beta = 
      0.116) and executive function (beta = -0.139). Bivariate twin modelling showed
      well-being shared a small environmental correlation with motor coordination and a
      small genetic correlation with working memory. Trivariate twin modelling showed
      well-being shared a small genetic correlation with inhibition, whereas depression
      and anxiety symptoms shared a small environmental correlation with inhibition.
      The remaining variance was mostly driven by unique G and/or E variance. Overall,
      well-being and depression and anxiety symptoms show both independent and shared
      relationships with cognitive functions but this is largely attributable to unique
      G or E variance and small shared G/E variance between pairs of variables.

PMID- 27690267
TI  - Effect of feed supplementation with kynurenic acid on the morphology of the
      liver, kidney and gills in rainbow trout (Oncorhynchus mykiss Walbaum, 1792),
      healthy and experimentally infected with Yersinia ruckeri.
AB  - Kynurenic acid (KYNA) is an endogenous substance produced on the kynurenine
      pathway which is primarily known for its neuroactive properties. Recently, it has
      been proven that KYNA is a selective ligand for G protein-coupled receptor (GPR
      35), presented on immunocompetent cells such as T lymphocytes. This opens up new
      possibilities of its application as an immunostimulating substance in
      aquaculture. Thus far, no histopathological investigations in fish have been
      completed to evaluate influence of KYNA supplementation in feed. This study has
      been undertaken to determine the effect of feed supplementation with KYNA (2.5,
      25, 250 mg kg-1 of feed) for 28 days on the liver, gills and kidney in healthy
      fish and experimentally infected with Yersinia ruckeri. In a control group were
      observed a fatty liver, which is natural for this fish species in the autumn and
      winter season. As the dose of the supplement was increased, the fat liver
      changed, it decreased or completely disappeared. Additionally, inflammatory
      changes occurred in all the analysed organs, and their intensification was dose
      dependent. In the fish experimentally infected, KYNA caused aggravation of the
      signs in the liver, kidneys and gills, and the effect was dose dependent. The
      results implicate that KYNA may be a stressor for fish.

PMID- 27690268
TI  - The role of dispersive forces determining the energetics of adsorption in Ti
      zeolites.
AB  - Ti-zeolites are interesting materials because of their key role in partial
      oxidation reactions, as well as under a fundamental point of view being regarded
      as single site catalysts. Both experimental and computational approaches have
      been widely applied to the characterization of their active sites, reaching a
      level of knowledge unmatchable by most other important catalysts. However,
      several questions are still open, being a proper energetic simulation of the
      adsorption process of simple molecules, fitting with the experimental outcomes,
      still missing. The present work wants to underline the role of dispersive forces
      in correctly determining the adsorption energies of H2 O and NH3 in Ti chabazite:
      first dispersive contributions have been included through an ONIOM scheme,
      comparing the results from semiempirical Grimme scheme and fully ab initio MP2.
      Being the key contribution of dispersion proved, a fully periodic, Grimme
      dispersions inclusive approach has been applied, coming to results close to the
      experimental values. (c) 2016 Wiley Periodicals, Inc.

PMID- 27690269
TI  - The effects of Symbiodinium (Pyrrhophyta) identity on growth, survivorship, and
      thermal tolerance of newly settled coral recruits.
AB  - For many coral species, the obligate association with phylogenetically diverse
      algal endosymbiont species is dynamic in time and space. Here, we used controlled
      laboratory inoculations of newly settled, aposymbiotic corals (Orbicella
      faveolata) with two cultured species of algal symbiont (Symbiodinium
      microadriaticum and S. minutum) to examine the role of symbiont identity on
      growth, survivorship, and thermal tolerance of the coral holobiont. We evaluated
      these data in the context of Symbiodinium photophysiology for 9 months post
      settlement and also during a 5-d period of elevated temperatures Our data show
      that recruits that were inoculated with S. minutum grew significantly slower than
      those inoculated with S. microadriaticum (occasionally co-occurring with S.
      minutum), but that there was no difference in survivorship of O. faveolata polyps
      infected with Symbiodinium. However, photophysiological metrics (?Fv/F'm, the
      efficiency with which available light is used to drive photosynthesis and alpha,
      the maximum light utilization coefficient) were higher in those slower growing
      recruits containing S. minutum. These findings suggest that light use (i.e.,
      photophysiology) and carbon acquisition by the coral host (i.e., host growth) are
      decoupled, but did not distinguish the source of this difference. Neither
      Symbiodinium treatment demonstrated a significant negative effect of a 5-d
      exposure to temperatures as high as 32 degrees C under low light conditions
      similar to those measured at settlement habitats.

PMID- 27690270
TI  - Hepatotoxicity prediction by systems biology modeling of disturbed metabolic
      pathways using gene expression data.
AB  - The present study applies a systems biology approach for the in silico predictive
      modeling of drug toxicity on the basis of high-quality preclinical drug toxicity
      data with the aim of increasing the mechanistic understanding of toxic effects of
      compounds at different levels (pathway, cell, tissue, organ). The model
      development was carried out using 77 compounds for which gene expression data for
      treated primary human hepatocytes is available in the LINCS database and for
      which rodent in vivo hepatotoxicity information is available in the eTOX
      database. The data from LINCS were used to determine the type and number of
      pathways disturbed by each compound and to estimate the extent of disturbance
      (network perturbation elasticity), and were used to analyze the correspondence
      with the in vivo information from eTOX. Predictive models were developed through
      this integrative analysis, and their specificity and sensitivity were assessed.
      The quality of the predictions was determined on the basis of the area under the
      curve (AUC) of plots of true positive vs. false positive rates (ROC curves). The
      ROC AUC reached values of up to 0.9 (out of 1.0) for some hepatotoxicity
      endpoints. Moreover, the most frequently disturbed metabolic pathways were
      determined across the studied toxicants. They included, e.g., mitochondrial beta
      oxidation of fatty acids and amino acid metabolism. The process was exemplified
      by successful predictions on various statins. In conclusion, an entirely new
      approach linking gene expression alterations to the prediction of complex organ
      toxicity was developed and evaluated.

PMID- 27690265
TI  - DNA methylation-based measures of biological age: meta-analysis predicting time
      to death.
AB  - Estimates of biological age based on DNA methylation patterns, often referred to
      as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age
      in humans. We previously demonstrated that independent of chronological age,
      epigenetic age assessed in blood predicted all-cause mortality in four human
      cohorts. Here, we expanded our original observation to 13 different cohorts for a
      total sample size of 13,089 individuals, including three racial/ethnic groups. In
      addition, we examined whether incorporating information on blood cell composition
      into the epigenetic age metrics improves their predictive power for mortality.
      All considered measures of epigenetic age acceleration were predictive of
      mortality (p<=8.2x10-9), independent of chronological age, even after adjusting
      for additional risk factors (p<5.4x10-4), and within the racial/ethnic groups
      that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic
      age estimates that incorporated information on blood cell composition led to the
      smallest p-values for time to death (p=7.5x10-43). Overall, this study a)
      strengthens the evidence that epigenetic age predicts all-cause mortality above
      and beyond chronological age and traditional risk factors, and b) demonstrates
      that epigenetic age estimates that incorporate information on blood cell counts
      lead to highly significant associations with all-cause mortality.

PMID- 27690271
TI  - Chiral N,N'-Dioxide-Organocatalyzed Regio-, Diastereo- and Enantioselective
      Michael Addition-Alkylation Reaction.
AB  - A highly regio-, diastereo- and enantioselective Michael addition-alkylation
      reaction between alpha-substituted cyano ketones and (Z)-bromonitrostyrenes has
      been realized by using a chiral N,N'-dioxide as organocatalyst. A variety of
      substrates performed well in this reaction, and the corresponding
      multifunctionalized chiral 2,3-dihydrofurans were obtained in up to 95 % yield
      with 95:5 dr and 93 % ee.

PMID- 27690273
TI  - High Spatial Resolution Imaging of Transient Thermal Events Using Materials with
      Thermal Memory.
AB  - The working principle of a new kind of nanothermometer is experimentally
      demonstrated using bistable materials with thermal memory. This thermometry
      approach allows for acquiring sub-wavelength resolution images of fast, transient
      heating events.

PMID- 27690272
TI  - Considerations for successful cancer immunotherapy in aged hosts.
AB  - Immunotherapy is now experiencing unprecedented successes in treating various
      cancers based on new understandings of cancer immunopathogenesis. Nonetheless,
      although ageing is the biggest risk factor for cancer, the majority of cancer
      immunotherapy preclinical studies are conducted in young hosts. This review will
      explore age-related changes in immunity as they relate to cancer immune
      surveillance, immunopathogenesis and responses to immunotherapy. Although it is
      recognized that declining T cell function with age poses a great challenge to
      developing effective age-related cancer immunotherapies, examples of successful
      approaches to overcome this hurdle have been developed. Further, it is now
      recognized that immune functions do not simply decline with age, but rather
      change in ways than can be detrimental. For example, with age, specific immune
      cell populations with detrimental functions can become predominant (such as cells
      producing proinflammatory cytokines), suppressive cells can become more numerous
      or more suppressive (such as myeloid-derived suppressor cells), drugs can affect
      aged immune cells distinctly and the aged microenvironment is becoming recognized
      as a significant barrier to address. Key developments in these and other areas
      will be surveyed as they relate to cancer immunotherapy in aged hosts, and areas
      in need of more study will be assessed with some speculations for the future. We
      propose the term 'age-related immune dysfunction' (ARID) as best representative
      of age-associated changes in immunity.

PMID- 27690274
TI  - Activation of adenylate cyclase-cyclic AMP-protein kinase A signaling by
      corticotropin-releasing factor within the dorsolateral bed nucleus of the stria
      terminalis is involved in pain-induced aversion.
AB  - Pain is a complex experience involving sensory and affective components. Although
      the neuronal mechanisms underlying the sensory component of pain have been
      extensively studied, those underlying its affective component have yet to be
      elucidated. Recently, we reported that corticotrophin-releasing factor (CRF)
      induced depolarization in type II neurons within the dorsolateral bed nucleus of
      the stria terminalis (dlBNST) is critical for pain-induced aversive responses in
      rats. However, the intracellular signaling underlying the excitatory effects of
      CRF and the contribution of such signaling to the induction of pain-induced
      aversion remain unclear. In the present study, we addressed these issues by
      conducting whole-cell patch-clamp recordings in rat brain slices and by
      undertaking behavioral pharmacological analyses. Intracellular perfusion of
      protein kinase A (PKA) inhibitor Rp-cyclic adenosine monophosphorothioate (Rp
      cAMPS) or KT5720 suppressed the excitatory effects of CRF in type II dlBNST
      neurons, and bath application of Rp-cAMPS also suppressed it. In addition, bath
      application of forskolin, an adenylate cyclase (AC) activator, mimicked the
      effects of CRF, and pretreatment with forskolin diminished the excitatory effects
      of CRF. Furthermore, a conditioned place aversion (CPA) test showed that co
      administration of Rp-cAMPS with CRF into the dlBNST suppressed CRF-induced CPA.
      Intra-dlBNST injection of Rp-cAMPS also suppressed pain-induced CPA. These
      results suggest that CRF increases excitability of type II dlBNST neurons through
      activation of the AC-cAMP-PKA pathway, thereby causing pain-induced aversive
      responses. The present findings shed light on the neuronal mechanisms underlying
      the negative affective component of pain and may provide therapeutic targets for
      treating intractable pain accompanied by psychological factors.

PMID- 27690275
TI  - Acidification and warming affect prominent bacteria in two seasonal phytoplankton
      bloom mesocosms.
AB  - In contrast to clear stimulatory effects of rising temperature, recent studies of
      the effects of CO2 on planktonic bacteria have reported conflicting results. To
      better understand the potential impact of predicted climate scenarios on the
      development and performance of bacterial communities, we performed bifactorial
      mesocosm experiments (pCO2 and temperature) with Baltic Sea water, during a
      diatom dominated bloom in autumn and a mixed phytoplankton bloom in summer. The
      development of bacterial community composition (BCC) followed well-known algal
      bloom dynamics. A principal coordinate analysis (PCoA) of bacterial OTUs
      (operational taxonomic units) revealed that phytoplankton succession and
      temperature were the major variables structuring the bacterial community whereas
      the impact of pCO2 was weak. Prokaryotic abundance and carbon production, and
      organic matter concentration and composition were partly affected by temperature
      but not by increased pCO2 . However, pCO2 did have significant and potentially
      direct effects on the relative abundance of several dominant OTUs; in some cases,
      these effects were accompanied by an antagonistic impact of temperature. Our
      results suggest the necessity of high-resolution BCC analyses and statistical
      analyses at the OTU level to detect the strong impact of CO2 on specific
      bacterial groups, which in turn might also influence specific organic matter
      degradation processes.

PMID- 27690276
TI  - Characterization and biocompatibility evaluation of bacterial cellulose-based
      wound dressing hydrogel: effect of electron beam irradiation doses and
      concentration of acrylic acid.
AB  - The use of bacterial cellulose (BC)-based hydrogel has been gaining attention
      owing to its biocompatibility and biodegradability. This study was designed to
      investigate the effect of radiation doses and acrylic acid (AA) composition on in
      vitro and in vivo biocompatibility of BC/AA as wound dressing materials. Physical
      properties of the hydrogel, that is, thickness, adhesiveness, rate of water vapor
      transmission, and swelling were measured. Moreover, the effect of these
      parameters on skin irritation and sensitization, blood compatibility, and
      cytotoxicity was studied. Increased AA content and irradiation doses increased
      the thickness, crosslinking density, and improved the mechanical properties of
      the hydrogel, but reduced its adhesiveness. The swelling capacity of the hydrogel
      increased significantly with a decrease in the AA composition in simulated wound
      fluid. The water vapor permeability of polymeric hydrogels was in the range of
      2035-2666 [g/(m-2  day-1 )]. Dermal irritation and sensitization test
      demonstrated that the hydrogel was nonirritant and nonallergic. The BC/AA
      hydrogel was found to be nontoxic to primary human dermal fibroblast skin cells
      with viability >88% and was found to be biocompatible with blood with a low
      hemolytic index (0.80-1.30%). Collectively, these results indicate that these
      hydrogels have the potential to be used as wound dressings. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2553-2564,
      2017.

PMID- 27690278
TI  - Controlled Synthesis of Core-Shell Carbon@MoS2 Nanotube Sponges as High
      Performance Battery Electrodes.
AB  - Heterogeneous inorganic nanotube structures consisting of multiwalled carbon
      nanotubes coated by long, continuous MoS2 sheets with tunable sheet number are
      synthesized using a carbon-nanotube sponge as a template. The resulting 3D porous
      hybrid sponges have potential applications as high-performance freestanding
      anodes for Li-ion batteries with excellent specific capacity and cycling
      stability.

PMID- 27690277
TI  - Direct Mannich-Type Reactions Promoted by Frustrated Lewis Acid/Bronsted Base
      Catalysts.
AB  - Direct Mannich-type reactions that afford both alpha- and beta-amino esters by
      the reaction of a broad range of carbonyl compounds and aldimines are disclosed.
      The transformation is promoted by a sterically frustrated Lewis acid/Bronsted
      base pair, which is proposed to operate cooperatively: Within the catalyst
      complex, an enolate is generated that then reacts with a hydrogen-bond-activated
      imine. Noncovalent interactions between reactants and the catalyst provide
      selectivity and new opportunities for future catalyst design.

PMID- 27690279
TI  - Ectopic models for endochondral ossification: comparing pellet and alginate bead
      culture methods.
AB  - Key aspects of native endochondral bone development and fracture healing can be
      mimicked in mesenchymal stem cells (MSCs) through standard in vitro chondrogenic
      induction. Exploiting this phenomenon has recently emerged as an attractive
      technique to engineer bone tissue, however, relatively little is known about the
      best conditions for doing so. The objective of the present study was to compare
      the bone-forming capacity and angiogenic induction of hypertrophic cell
      constructs containing human adipose-derived stem cells (hASCs) primed for
      chondrogenesis in two different culture systems: high-density pellets and
      alginate bead hydrogels. The hASC constructs were subjected to 4 weeks of
      identical chondrogenic induction in vitro, encapsulated in an agarose carrier,
      and then implanted subcutaneously in immune-compromised mice for 8 weeks to
      evaluate their endochondral potential. At the time of implantation, both pellets
      and beads expressed aggrecan and type II collagen, as well as alkaline
      phosphatase (ALP) and type X collagen. Interestingly, ASCs in pellets formed a
      matrix containing higher glycosaminoglycan and collagen contents than that in
      beads, and ALP activity per cell was higher in pellets. However, after 8 weeks in
      vivo, pellets and beads induced an equivalent volume of mineralized tissue and a
      comparable level of vascularization. Although osteocalcin and osteopontin
      positive osteogenic tissue and new vascular growth was found within both types of
      constructs, all appeared to be better distributed throughout the hydrogel beads.
      The results of this ectopic model indicate that hydrogel culture may be an
      attractive alternative to cell pellets for bone tissue engineering via the
      endochondral pathway. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27690281
TI  - Assessment of risk factors for oro-facial pain and recent developments in
      classification: implications for management.
AB  - Oro-facial pain research has during the last decades provided important novel
      insights into the basic underlying mechanisms, the need for standardised
      diagnostic procedures and classification systems, and multiple treatment options
      for successful rehabilitation of the patient in pain. Notwithstanding the
      significant progress in our knowledge spanning from molecules to chair, there may
      also be limitations in our ability to integrate and interpret the tremendous
      amount of new data and information, in particular in terms of the clinical
      implications and overriding conceptual models for oro-facial pain. The aim of the
      present narrative review is to briefly summarise some of the current thoughts on
      oro-facial pain mechanisms and recent attempts to identify biomarkers and risk
      factors leading to the proposal of a new risk assessment diagram for oro-facial
      pain (RADOP) and a provocative new concept based on stochastic variation between
      multiple risk factors. Finally, the implications for novel management strategies
      will briefly be discussed.

PMID- 27690280
TI  - Van der Waals Force Isolation of Monolayer MoS2.
AB  - Monolayer MoS2 can effectively screen the vdW interaction of underlying
      substrates with external systems by >90% because of the substantial increase in
      the separation between the substrate and external systems due to the presence of
      the monolayer. This substantial screening of vdW interactions by MoS2 monolayer
      is different from what reported at graphene.

PMID- 27690282
TI  - Validation of a Chromosomal Microarray for Prenatal Diagnosis Using a Prospective
      Cohort of Pregnancies with Increased Risk for Chromosome Abnormalities.
AB  - AIM: Validation of a chromosomal microarray for improved prenatal diagnosis for
      chromosomal abnormalities among high-risk pregnancies. METHODS: A cohort of 213
      pregnancies was investigated by chromosomal microarray and the results were
      compared with quantitative fluorescent polymerase chain reaction (QF-PCR),
      karyotype, and 850K single-nucleotide polymorphism microarray results. The
      detection limit of mosaicism was determined by assaying different trisomy mosaic
      constructs down to ~12%. Imprecision estimates from replicates of mean log2 ratio
      values for a 200 kb deletion and 400 kb duplication were determined by evaluating
      the coefficient of variation (CV%). RESULTS: Excluding pregnancies with
      aneuploidy, the chromosomal microarray detected 19/213 (8.9%) pregnancies with
      copy number abnormalities. These were classified as pathogenic in 11/213 (5.2%)
      cases, as variants of uncertain significance in 4/213 (1.9%) cases, and as likely
      benign in 4/213 (1.9%) cases. In 15/213 (7.0%) pregnancies, these abnormalities
      were not detectable by karyotype. Importantly, 8/11 (72.7%) of the pathogenic
      abnormalities detected by chromosomal microarray were only detectable by this
      modality. There were no false-positive results and only eight false-negative
      results. The chromosomal microarray showed excellent sensitivity (96.2%) and
      specificity (100.0%). The lower detection limit for mosaicism was ~12%.
      Imprecision for the 0.2 Mb deletion (11.6 CV%) and 0.4 Mb duplication (5.9 CV%)
      was very low. CONCLUSION: This chromosomal microarray showed excellent diagnostic
      performance with improved detection rates compared to karyotyping for prenatal
      diagnosis of clinically relevant fetal chromosomal abnormalities.

PMID- 27690284
TI  - Recovery of functionally-active protein from inclusion bodies using a thermal
      cycling method.
AB  - Heterologous overexpression of genes in Escherichia coli has made it possible to
      obtain high titers of recombinant proteins. However, this can result in the
      formation of aggregated protein particles known as 'inclusion bodies'. Protein
      sequestered as inclusion body is inactive and needs to be converted back to its
      functional form by refolding using appropriate techniques. In the current study
      inclusion bodies of the enzyme aminoglycoside nucleotidyl transferase (or ANT(2")
      Ia) were first solubilized in urea and subsequently subjected to thermal cycling
      under controlled conditions as part of the refolding strategy. Thermal cycling
      led to disaggregation of the individual protein chains and simultaneously
      refolding the released protein molecules to their native state. The optimum
      condition was identified as 10-80 degrees C thermal cycling at 3 degrees C s-1
      for 2 h. Enzyme activity measurements showed that thermal cycling under optimized
      conditions resulted in 257% activity recovery when compared with nonrefolded
      protein. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog.,
      33:133-139, 2017.

PMID- 27690283
TI  - Sexual Function, Contraception, Relationship, and Lifestyle in Female Medical
      Students.
AB  - BACKGROUND: We undertook to study possible determinants of female sexual
      dysfunction (FSD) in a large cohort of female medical students from German
      speaking countries. METHODS: We conducted an online questionnaire-based anonymous
      survey in a cohort of >2600 female medical students enrolled at German-speaking
      universities. The questionnaire comprised the Female Sexual Function Index (FSFI)
      plus additional questions regarding contraception, sexual activity, age, height,
      weight, lifestyle, activity at work, sexuality and emotional interaction with a
      steady partner, pregnancy history and plans, health problems, and self
      acceptance. Data analysis employed descriptive statistics, univariate and
      multivariate analyses, and standard nonparametric tests. RESULTS: Of the 2612
      respondents aged <=30 years included in the analysis (mean age [standard
      deviation], 23.5 [2.5] years), 38.7% of the overall cohort and 33.5% of the
      sexually active subcohort (91.8% of all students) were at risk for FSD (FSFI
      score <26.55). Multivariate analysis revealed the following significant factors
      to be associated with the FSFI: alcohol consumption, level of fitness, use of
      contraception, steady relationship, and self-acceptance (overall cohort and
      sexually active subcohort); smoking (overall cohort only); and body mass index
      and activity at work (sexually active subcohort only). CONCLUSIONS: Almost 40% of
      German-speaking female medical students are at risk for FSD. Contraception,
      smoking, alcohol, steady relationship, physical fitness, and self-acceptance are
      significantly associated with the FSFI total score. Being in a steady
      relationship, better physical fitness, higher activity at work, and subjectively
      positive self-acceptance, in particular, are associated with higher FSFI total
      scores, that is, with less risk for sexual dysfunction.

PMID- 27690285
TI  - Individual joint contribution to body weight support in the affected lower limb
      during walking in post-stroke hemiplegia.
AB  - OBJECTIVE: Patients with post-stroke hemiplegia have difficulty with body weight
      support during walking. However, it is unclear which intra-limb strategy for body
      weight support tends to predominate, and how the intra-limb strategy is related
      to gait function. Support moment and individual joint contribution to support
      moment are the parameters that reflect intra-limb strategy for body weight
      supporting. The aim of this study was to test whether support moment and
      individual joint contributions differed between post-stroke subjects with
      different gait function. METHOD: Laboratory gait analysis was performed for 14
      non-hemiplegic elderly (NE) and 12 post-stroke hemiplegic elderly walking without
      cane (HNC) and 11 walking with a cane (HWC). Data were obtained for the vertical
      ground reaction force (vGRF) curve, 1st peak and 2nd peak of vGRF and
      corresponding temporal occurrences. Support moment (Ms) was numerical sum of hip
      extension, knee extension, and ankle plantar flexion moment. Individual joint
      contribution was calculated as the ratio of each joint moment to support moment.
      At temporal occurrences of vGRF peaks, Ms and individual joint contribution to Ms
      were calculated. Ms and individual joint contribution to Ms were compared among
      NE, HNC and HWC groups. Each subject's characteristics of individual joint
      contribution to Ms were explored. RESULTS: At the 1st peak of vGRF, support
      moments were similar among the three groups. However, the hip contributions were
      significantly greater in the NE group than in the other two groups, the ankle
      contributions were significantly greater in the HNC group than in the NE group.
      Notably, some of the subjects with post-stroke hemiplegia showed atypical
      characteristics that did not correspond to the group characteristics. CONCLUSION:
      Observing support moment and individual joint contribution is helpful to
      ascertain not only group characteristics, but also individual characteristics of
      intra-limb strategy for weight support in patients with post-stroke hemiplegia.

PMID- 27690286
TI  - Effects of physical exercise on musculoskeletal disorders, stress and quality of
      life in workers.
AB  - BACKGROUND: The effect of physical exercise in the workplace (PEW) on health
      promotion of workers is contradictory. OBJECTIVE: To evaluate the effects of the
      PEW in musculoskeletal disorders (MSDs), perception of stress and quality of life
      in workers. METHODS: The participants were divided into two groups: control group
      (n = 46) including non-participant workers of the PEW program, and PEW group (n =
      50) including workers who regularly participate in the exercise program. All
      workers answered the Nordic general questionnaire, the perceived stress scale and
      the quality-of-life questionnaire. RESULTS: The PEW group reported a lower
      prevalence of MSDs for the trunk in the last 7 days and 12 months (p = 0.021 and
      p = 0.001, respectively), and for the upper limbs in the last 12 months (p =
      0.001) compared with the control group . The results for the perception of stress
      and quality of life showed no significant differences between the groups.
      CONCLUSION: PEW is a potential method to reduce MSDs in workers, but it was not
      efficient in reducing stress levels or improving the quality of life of the
      workers.

PMID- 27690287
TI  - Feasibility of using low-cost portable particle monitors for measurement of fine
      and coarse particulate matter in urban ambient air.
AB  - : Exposure to ambient particulate matter (PM) is known as a significant risk
      factor for mortality and morbidity due to cardiorespiratory causes. Owing to
      increased interest in assessing personal and community exposures to PM, we
      evaluated the feasibility of employing a low-cost portable direct-reading
      instrument for measurement of ambient air PM exposure. A Dylos DC 1700 PM sensor
      was collocated with a Grimm 11-R in an urban residential area of Houston Texas.
      The 1-min averages of particle number concentrations for sizes between 0.5 and
      2.5 um (small size) and sizes larger than 2.5 um (large size) from a DC 1700 were
      compared with the 1-min averages of PM2.5 (aerodynamic size less than 2.5 um) and
      coarse PM (aerodynamic size between 2.5 and 10 um) concentrations from a Grimm 11
      R. We used a linear regression equation to convert DC 1700 number concentrations
      to mass concentrations, utilizing measurements from the Grimm 11-R. The estimated
      average DC 1700 PM2.5 concentration (13.2 +/- 13.7 ug/m3) was similar to the
      average measured Grimm 11-R PM2.5 concentration (11.3 +/- 15.1 ug/m3). The
      overall correlation (r2) for PM2.5 between the DC 1700 and Grimm 11-R was 0.778.
      The estimated average coarse PM concentration from the DC 1700 (5.6 +/- 12.1
      ug/m3) was also similar to that measured with the Grimm 11-R (4.8 +/- 16.5 ug/m3)
      with an r2 of 0.481. The effects of relative humidity and particle size on the
      association between the DC 1700 and the Grimm 11-R results were also examined.
      The calculated PM mass concentrations from the DC 1700 were close to those
      measured with the Grimm 11-R when relative humidity was less than 60% for both
      PM2.5 and coarse PM. Particle size distribution was more important for the
      association of coarse PM between the DC 1700 and Grimm 11-R than it was for
      PM2.5. IMPLICATIONS: The performance of a low-cost particulate matter (PM) sensor
      was evaluated in an urban residential area. Both PM2.5 and coarse PM (PM10-2.5)
      mass concentrations were estimated using a DC1700 PM sensor. The calculated PM
      mass concentrations from the number concentrations of DC 1700 were close to those
      measured with the Grimm 11-R when relative humidity was less than 60% for both
      PM2.5 and coarse PM. Particle size distribution was more important for the
      association of coarse PM between the DC 1700 and Grimm 11-R than it was for
      PM2.5.

PMID- 27690288
TI  - The distribution of melanopsin (OPN4) protein in the human brain.
AB  - Until now, melanopsin (OPN4) - a specialized photopigment being responsive
      especially to blue light wavelengths - has not been found in the human brain at
      protein level outside the retina. More specifically, OPN4 has only been found in
      about 2% of retinal ganglion cells (i.e. in intrinsically photosensitive retinal
      ganglion cells), and in a subtype of retinal cone-cells. Given that Allen
      Institute for Brain Science has described a wide distribution of OPN4 mRNA in two
      human brains, we aimed to investigate whether OPN4 is present in the human brain
      also at protein level. Western blotting and immunohistochemistry, as well as
      immunoelectron microscopy, were used to analyse the existence and distribution of
      OPN4 protein in 18 investigated areas of the human brain in samples obtained in
      forensic autopsies from 10 male subjects (54 +/- 3.5 years). OPN4 protein
      expression was found in all subjects, and, furthermore, in 5 out of 10 subjects
      in all investigated brain areas localized in membranous compartments and
      cytoplasmic vesicles of neurons. To our opinion, the wide distribution of OPN4 in
      central areas of the human brain evokes a question whether ambient light has
      important straight targets in the human brain outside the retinohypothalamic
      tract (RHT). Further studies are, however, needed to investigate the putative
      physiological phototransductive actions of inborn OPN4 protein outside the RHT in
      the human brain.

PMID- 27690289
TI  - Emergency Medical Dispatchers Can Obtain Accurate Pediatric Weights from 9-1-1
      Callers.
AB  - BACKGROUND: Prehospital pediatric drug dosing errors affect 56,000 U.S. children
      annually. An accurate weight is the first step in accurate dosing. To date, the
      accuracy of Emergency Medical Dispatcher (EMD) obtained weights has not been
      evaluated. We hypothesized that EMD could obtain accurate pediatric weights.
      METHODS: We used a convenience sample of patients 12 years and younger that were
      transported by EMS to one children's hospital. EMD obtained patient weight (DW)
      from the 9-1-1 caller. Paramedics reported their estimate of the patient's weight
      on arrival to the hospital (PW). The DW and PW were compared to the hospital
      scale weight (HW) for accuracy. RESULTS: A total of 197 patients were included.
      Parent/guardians were the most frequent 9-1-1 callers (74%). The most frequent
      method utilized by paramedics to obtain patient weight was to ask a family
      member. For 0-2 year olds, the mean differences between HW and DW/PW were 0.239kg
      (SD 3.117)/ -0.374 (SD 2.528). For 3-7 year olds, the mean differences between HW
      and DW/PW were 0.041kg (SD 4.684)/1.007 (SD 2.466). For 8-11 year olds the mean
      difference between HW and DW/PW was 2.768 kg (SD 10.926)/ 1.919 (SD 6.909).
      CONCLUSION: EMD were able to obtain pediatric patient weights with relative
      accuracy for patients 0-7 year old. Using this EMD-obtained weight to carry out a
      drug dose calculation would be unlikely to result in a clinically significant
      dose error in the vast majority of cases. Communicating an EMD-obtained weight to
      EMS crews en route to a pediatric patient offers additional preparation time for
      drug calculations, which could improve accuracy.

PMID- 27690290
TI  - Non-Fourier based thermal-mechanical tissue damage prediction for thermal
      ablation.
AB  - Prediction of tissue damage under thermal loads plays important role for thermal
      ablation planning. A new methodology is presented in this paper by combing non
      Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid
      motion of dynamics to predict and analyze thermal distribution, thermal-induced
      mechanical deformation and thermal-mechanical damage of soft tissues under
      thermal loads. Simulations and comparison analysis demonstrate that the proposed
      methodology based on the non-Fourier bio-heat transfer can account for the
      thermal-induced mechanical behaviors of soft tissues and predict tissue thermal
      damage more accurately than classical Fourier bio-heat transfer based model.

PMID- 27690291
TI  - Differences According to Sex in Perspectives and Beliefs on Osteoporosis: A Cross
      Sectional Survey Study.

PMID- 27690292
TI  - In Search of Autism's Roots.

PMID- 27690293
TI  - Socioeconomic evaluation of vagus stimulation: A controlled national study.
AB  - PURPOSE: We aimed to determine the health costs and social outcomes in terms of
      education, employment and income level after insertion of a vagus nerve
      stimulator (VNS) in patients with epilepsy. METHODS: This is a case-control study
      using Danish health care and socioeconomic register data. The analysis of the
      effect involved a comparison of the health care costs, occupation and income
      status of VNS-treated epilepsy patients with those of a control group of epilepsy
      patients who had a VNS implanted during the 12 months before the index date (pre
      period) and during the two years after the index date (post-period). RESULTS: 101
      patients who had undergone VNS implantation and 390 control patients were
      included. VNS implantation was associated with fewer inpatient admissions and
      emergency room visits and less frequent use of prescription medication compared
      with epilepsy patients without VNS implantation. VNS implantation was not
      associated with changes in occupational status (including employment and income).
      In fact, the number of people on disability pension increased during the period.
      CONCLUSIONS: VNS implantation in people with epilepsy is associated with reduced
      health care use, but not with occupational or social status.

PMID- 27690294
TI  - Phase III randomized trial of autologous cytokine-induced killer cell
      immunotherapy for newly diagnosed glioblastoma in Korea.
AB  - PURPOSE: Adoptive cell immunotherapy involves an ex vivo expansion of autologous
      cytokine-induced killer (CIK) cells before their reinfusion into the host. We
      evaluated the efficacy and safety of CIK cell immunotherapy with radiotherapy
      temozolomide (TMZ) for the treatment of newly diagnosed glioblastomas.
      EXPERIMENTAL DESIGN: In this multi-center, open-label, phase 3 study, we randomly
      assigned patients with newly diagnosed glioblastoma to receive CIK cell
      immunotherapy combined with standard TMZ chemoradiotherapy (CIK immunotherapy
      group) or standard TMZ chemoradiotherapy alone (control group). The efficacy
      endpoints were analyzed in the intention-to-treat set and in the per protocol
      set. RESULTS: Between December 2008 and October 2012, a total of 180 patients
      were randomly assigned to the CIK immunotherapy (n = 91) or control group (n =
      89). In the intention-to-treat analysis set, median PFS was 8.1 months (95%
      confidence interval (CI), 5.8 to 8.5 months) in the CIK immunotherapy group, as
      compared to 5.4 months (95% CI, 3.3 to 7.9 months) in the control group (one
      sided log-rank, p = 0.0401). Overall survival did not differ significantly
      between two groups. Grade 3 or higher adverse events, health-related quality of
      life and performance status between two groups did not show a significant
      difference. CONCLUSIONS: The addition of CIK cells immunotherapy to standard
      chemoradiotherapy with TMZ improved PFS. However, the CIK immunotherapy group did
      not show evidence of a beneficial effect on overall survival.

PMID- 27690297
TI  - Improving needle biopsy accuracy in small renal mass using tumor-specific DNA
      methylation markers.
AB  - PURPOSE: The clinical management of small renal masses (SRMs) is challenging
      since the current methods for distinguishing between benign masses and malignant
      renal cell carcinomas (RCCs) are frequently inaccurate or inconclusive. In
      addition, renal cancer subtypes also have different treatments and outcomes. High
      false negative rates increase the risk of cancer progression and indeterminate
      diagnoses result in unnecessary and potentially morbid surgical procedures.
      EXPERIMENTAL DESIGN: We built a predictive classification model for kidney tumors
      using 697 DNA methylation profiles from six different subgroups: clear cell,
      papillary and chromophobe RCC, benign angiomylolipomas, oncocytomas, and normal
      kidney tissues. Furthermore, the DNA methylation-dependent classifier has been
      validated in 272 ex vivo needle biopsy samples from 100 renal masses (71% SRMs).
      RESULTS: In general, the results were highly reproducible (89%, n=70) in
      predicting identical malignant subtypes from biopsies. Overall, 98% of adjacent
      normals (n=102) were correctly classified as normal, while 92% of tumors (n=71)
      were correctly classified malignant and 86% of benign (n=29) were correctly
      classified benign by this classification model. CONCLUSIONS: Overall, this study
      provides molecular-based support for using routine needle biopsies to determine
      tumor classification of SRMs and support the clinical decision-making.

PMID- 27690296
TI  - Immune cells in liver regeneration.
AB  - After partial hepatectomy, hepatocytes proliferate to restore mass and function
      of the liver. Macrophages, natural killer (NK) cells, natural killer T (NKT)
      cells, dendritic cells (DC), eosinophils, gamma delta T (gammadeltaT) cells, and
      conventional T cells, as well as other subsets of the immune cells residing in
      the liver control liver regeneration, either through direct interactions with
      hepatocytes or indirectly by releasing inflammatory cytokines. Here, we review
      recent progress regarding the immune cells in the liver and their functions
      during liver regeneration.

PMID- 27690298
TI  - Glucuronidation and UGT isozymes in bladder: new targets for the treatment of
      uroepithelial carcinomas?
AB  - Bladder cancer has been linked to numerous toxins which can be concentrated in
      the bladder after being absorbed into the blood and filtered by the kidneys.
      Excessive carcinogenic load to the bladder urothelium may result in the
      development of cancer. However, enzymes within the bladder can metabolize
      carcinogens into substrates that are safer. Importantly, these proteins, namely
      the UGT's (uridine 5'-diphospho-glucuronosyltransferases), have been shown to
      possibly prevent bladder cancer. Also, studies have shown that the UGT1
      expression is decreased in uroepithelial carcinomas, which may allow for the
      accumulation of carcinogens in the bladder. In this review, we discuss the UGT
      system and its' protective role against bladder cancer, UGT genetic mutations
      that modulate risk from chemicals and environmental toxins, as well as targeting
      of the UGT enzymes by nuclear receptors.

PMID- 27690295
TI  - Factors and pathways involved in capacitation: how are they regulated?
AB  - In mammals, fertilization occurs via a comprehensive progression of events.
      Freshly ejaculated sperm have yet to acquire progressive motility or
      fertilization ability. They must first undergo a series of biochemical and
      physiological changes, collectively known as capacitation. Capacitation is a
      significant prerequisite to fertilization. During the process of capacitation,
      changes in membrane properties, intracellular ion concentration and the
      activities of enzymes, together with other protein modifications, induce multiple
      signaling events and pathways in defined media in vitro or in the female
      reproductive tract in vivo. These, in turn, stimulate the acrosome reaction and
      prepare spermatozoa for penetration of the egg zona pellucida prior to
      fertilization. In the present review, we conclude all mainstream factors and
      pathways regulate capacitation and highlight their crosstalk. We also summarize
      the relationship between capacitation and assisted reproductive technology or
      human disease. In the end, we sum up the open questions and future avenues in
      this field.

PMID- 27690300
TI  - Correlation analysis between 2D and quasi-3D gamma evaluations for both intensity
      modulated radiation therapy and volumetric modulated arc therapy.
AB  - The aim of this work was to investigate correlations between 2D and quasi-3D
      gamma passing rates. A total of 20 patients (10 prostate cases and 10 head and
      neck cases, H&N) were retrospectively selected. For each patient, both intensity
      modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)
      plans were generated. For each plan, 2D gamma evaluation with radiochromic films
      and quasi-3D gamma evaluation with fluence measurements were performed with both
      2%/2 mm and 3%/3 mm criteria. Gamma passing rates were grouped together according
      to delivery techniques and treatment sites. Statistical analyses were performed
      to examine the correlation between 2D and quasi-3D gamma evaluations.
      Statistically significant difference was observed between delivery techniques
      only in the quasi-3D gamma passing rates with 2%/2 mm. Statistically significant
      differences were observed between treatment sites in the 2D gamma passing rates
      (differences of less than 8%). No statistically significant correlations were
      observed between 2D and quasi-3D gamma passing rates except the VMAT group and
      the group including both IMRT and VMAT with 3%/3 mm (r = 0.564 with p = 0.012 for
      theVMAT group and r = 0.372 with p = 0.020 for the group including both IMRT and
      VMAT), however, those were not strong. No strong correlations were observed
      between 2D and quasi-3D gamma evaluations.

PMID- 27690301
TI  - MiR-128 reverses the gefitinib resistance of the lung cancer stem cells by
      inhibiting the c-met/PI3K/AKT pathway.
AB  - Gefitinib is a first line anti-tumor drug used for the treatment of patients with
      non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, the drug
      resistance to gefitinib limits its clinical application. Here, we observed the
      CSCs of PC9 are obviously resistant to gefitinib compared with the non-CSCs.
      Furthermore, we found the gefitinib failed to suppress the PI3K/AKT pathway in
      the PC9-CSCs. Mechanically, we showed significant down-regulation of miR-128 in
      the PC9-CSCs compared with the non-CSCs. Overexpression of miR-128 significantly
      increased the sensitivity of PC9-CSCs to gefitinib-induced apoptosis. In
      addition, the gene of c-met was proved to be directly inhibited by miR-128.
      Enforced expression of c-met could "rescue" the miR-128 promoted apoptosis and
      cleavage of caspases in PC9-CSCs treated with gefitinib. Thus, these results
      indicate that the miR-128/c-met pathway enhances the gefitinib sensitivity of the
      lung cancer stem cells by suppressing the PI3K/AKT pathway.

PMID- 27690302
TI  - Identification of novel prognostic indicators for triple-negative breast cancer
      patients through integrative analysis of cancer genomics data and protein
      interactome data.
AB  - Triple negative breast cancers (TNBCs) are highly heterogeneous and aggressive
      without targeted treatment. Here, we aim to systematically dissect TNBCs from a
      prognosis point of view by building a subnetwork atlas for TNBC prognosis through
      integrating multi-dimensional cancer genomics data from The Cancer Genome Atlas
      (TCGA) project and the interactome data from three different interaction
      networks. The subnetworks are represented as the protein-protein interaction
      modules perturbed by multiple genetic and epigenetic interacting mechanisms
      contributing to patient survival. Predictive power of these subnetwork-derived
      prognostic models is evaluated using Monte Carlo cross-validation and the
      concordance index (C-index). We uncover subnetwork biomarkers of low oncogenic
      GTPase activity, low ubiquitin/proteasome degradation, effective protection from
      oxidative damage, and tightly immune response are linked to better prognosis.
      Such a systematic approach to integrate massive amount of cancer genomics data
      into clinical practice for TNBC prognosis can effectively dissect the molecular
      mechanisms underlying TNBC patient outcomes and provide potential opportunities
      to optimize treatment and develop therapeutics.

PMID- 27690299
TI  - On the origin of myeloid-derived suppressor cells.
AB  - Myeloid-derived suppressor cells (MDSCs) have a strong immunosuppressive
      character that allows them to regulate immune responses and hinder overt
      inflammatory responses. In cancer, this leads to tumor immune evasion and disease
      progression. MDSCs come in at least two forms: monocytic (Mo-MDSCs) and
      granulocytic (G-MDSCs). The classical definition of MDSCs as immature myeloid
      cells blocked from differentiating has been challenged by recent studies
      suggesting that Mo-MDSCs and G-MDSCs may represent monocytes and granulocytes
      that have acquired immunosuppressive properties. The molecular mechanism behind
      their generation and their true origins are now widely debated. In this review we
      discuss the different proposed mechanisms of the generation of both types of
      MDSCs, with a special focus on human MDSCs in cancer.

PMID- 27690303
TI  - Intratumoral radiofrequency hyperthermia-enhanced direct chemotherapy of
      pancreatic cancer.
AB  - PURPOSE: To investigate the technical feasibility of using ultrasound-guided
      intratumoral radiofrequency hyperthermia (RFH) to enhance local chemotherapy of
      rat orthotopic pancreatic cancers. MATERIALS AND METHODS: Orthotopic pancreatic
      cancer masses were established by inoculating luciferase/mCherry labeled
      pancreatic cancer cells into the pancreatic tails of Lewis model rats via a
      laparotomy approach. Twenty-four rats with pancreatic cancer and 24 mice with
      subcutaneous pancreatic cancer xenografts in four study groups (n = 6/group)
      received various treatments: i) combination therapy of intratumoral MR imaging
      heating-guidewire-mediated RFH (42oC) plus local chemotherapy (gemcitabine); ii)
      intratumoral chemotherapy alone; iii) RFH alone; and (iv)phosphate-buffered
      saline (PBS). Transcutaneous ultrasound imaging was used to guide the treatment
      and subsequently follow changes in tumor sizes. Bioluminescence optical imaging
      was performed to follow photon signal changes. Sonographic and optical findings
      were correlated with histology at 14 days. RESULTS: Optical imaging demonstrated
      a significantly decreased bioluminescence signal in mice with combination therapy
      group, compared with the other control groups (0.51+/-0.18 VS 1.6+/-0.4 VS 3.18+/
      0.9 VS 3.5+/-0.96, p < 0.05). Ultrasound imaging showed the smallest tumor
      volumes of both mice and rat group with the combination therapy, compared with
      other control groups (0.62+/-0.16 VS 1.25+/-0.19 VS 2.28+/-0.25 VS 2.64+/-0.26, p
      < 0.05) and (0.75+/-0.18 VS 1.31+/-0.30 VS 1.61+/-0.28 VS 1.72+/-0.28, p < 0.05).
      Both imaging findings were confirmed by histologic correlation. CONCLUSION:
      Intratumoral RFH can augment the chemotherapeutic effect in an orthotopic
      pancreatic cancer model.

PMID- 27690305
TI  - Determining the relative orientation between the chemical shift anisotropy and
      heteronuclear dipolar tensors in static solids by SEDOR NMR.
AB  - The measurement of the dipolar interaction between two spins provides the
      distance between nuclei. A better structural picture emerges when the distance is
      combined with the orientation of the internuclear vector in the principal axis
      system of the chemical shift anisotropy tensor. The SEDOR experiment is used on a
      static sample of alanine to show that the orientation of the vector connecting
      the nitrogen and carboxylate carbon nuclei can be accurately determined in the
      CSA PAS of the 13C carboxylate spin.

PMID- 27690304
TI  - How exactly can computer simulation predict the kinematics and contact status
      after TKA? Examination in individualized models.
AB  - BACKGROUND: It is unknown whether a computer simulation with simple models can
      estimate individual in vivo knee kinematics, although some complex models have
      predicted the knee kinematics. The purposes of this study are first, to validate
      the accuracy of the computer simulation with our developed model during a
      squatting activity in a weight-bearing deep knee bend and then, to analyze the
      contact area and the contact stress of the tri-condylar implants for individual
      patients. METHODS: We compared the anteroposterior (AP) contact positions of
      medial and lateral condyles calculated by the computer simulation program with
      the positions measured from the fluoroscopic analysis for three implanted knees.
      Then the contact area and the stress including the third condyle were calculated
      individually using finite element (FE) analysis. FINDINGS: The motion patterns
      were similar in the simulation program and the fluoroscopic surveillance. Our
      developed model could nearly estimate the individual in vivo knee kinematics. The
      mean and maximum differences of the AP contact positions were 1.0mm and 2.5mm,
      respectively. At 120 degrees  of knee flexion, the contact area at the third
      condyle was wider than the both condyles. The mean maximum contact stress at the
      third condyle was lower than the both condyles at 90 degrees  and 120 degrees  of
      knee flexion. INTERPRETATION: Individual bone models are required to estimate in
      vivo knee kinematics in our simple model. The tri-condylar implant seems to be
      safe for deep flexion activities due to the wide contact area and low contact
      stress.

PMID- 27690306
TI  - Liver steatosis and nonalcoholic steatohepatitis: from pathogenesis to therapy.
AB  - Non-alcoholic fatty liver disease refers to a disease spectrum that ranges from
      steatosis to non-alcoholic steatohepatitis, which leads to fibrosis, cirrhosis
      and hepatocellular carcinoma. Given the increasing prevalence of obesity
      worldwide, the incidence of non-alcoholic fatty liver disease has become a world
      health problem. Non-alcoholic fatty liver disease is considered to be the hepatic
      manifestation of metabolic syndrome associated with insulin resistance, central
      obesity, and type 2 diabetes mellitus. Allegedly, insulin resistance plays a
      pivotal role in its pathogenesis. Here we highlight non-alcoholic fatty liver
      disease epidemiology and pathophysiology, its progression towards steatohepatitis
      with particular emphasis in liver fibrosis and participation of advanced
      glycation end products. The different treatments reported are described here as
      well. We conducted a search in PubMed with the terms steatohepatitis, steatosis
      advanced glycation end products, liver fibrosis and adipocytokines. Articles were
      selected according to their relevance.

PMID- 27690307
TI  - Ossicular Bone Damage and Hearing Loss in Rheumatoid Arthritis: A Correlated
      Functional and High Resolution Morphometric Study in Collagen-Induced Arthritic
      Mice.
AB  - Globally, a body of comparative case-control studies suggests that rheumatoid
      arthritis (RA) patients are more prone to developing hearing loss (HL). However,
      experimental evidence that supports this hypothesis is still lacking because the
      human auditory organ is not readily accessible. The aim of this study was to
      determine the association between bone damage to the ossicles of the middle ear
      and HL, using a widely accepted murine model of collagen-induced arthritis (RA
      mice). Diarthrodial joints in the middle ear were examined with microcomputer
      tomography (microCT), and hearing function was assessed by auditory brainstem
      response (ABR). RA mice exhibited significantly decreased hearing sensitivity
      compared to age-matched controls. Additionally, a significant narrowing of the
      incudostapedial joint space and an increase in the porosity of the stapes were
      observed. The absolute latencies of all ABR waves were prolonged, but mean
      interpeak latencies were not statistically different. The observed bone defects
      in the middle ear that were accompanied by changes in ABR responses were
      consistent with conductive HL. This combination suggests that conductive
      impairment is at least part of the etiology of RA-induced HL in a murine model.
      Whether the inner ear sustains bone erosion or other pathology, and whether the
      cochlear nerve sustains pathology await subsequent studies. Considering the fact
      that certain anti-inflammatories are ototoxic in high doses, monitoring RA
      patients' auditory function is advisable as part of the effort to ensure their
      well-being.

PMID- 27690308
TI  - The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture
      and tetramerizes histones.
AB  - The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric
      (H3/H4)2 histones onto newly-synthesized DNA during DNA replication. To
      understand the mechanism of the tri-subunit CAF-1 complex in this process, we
      investigated the protein-protein interactions within the CAF-1-H3/H4 architecture
      using biophysical and biochemical approaches. Hydrogen/deuterium exchange and
      chemical cross-linking coupled to mass spectrometry reveal interactions that are
      essential for CAF-1 function in budding yeast, and importantly indicate that the
      Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex. Cac1 alone
      not only binds H3/H4 with high affinity, but also promotes histone
      tetramerization independent of the other subunits. Moreover, we identify a
      minimal region in the C-terminus of Cac1, including the structured winged helix
      domain and glutamate/aspartate-rich domain, which is sufficient to induce
      (H3/H4)2 tetramerization. These findings reveal a key role of Cac1 in histone
      tetramerization, providing a new model for CAF-1-H3/H4 architecture and function
      during eukaryotic replication.

PMID- 27690310
TI  - Transformation of diclofenac in hybrid biofilm-activated sludge processes.
AB  - The biotransformation of diclofenac during wastewater treatment was investigated.
      Attached growth biomass from a carrier-filled compartment of a hybrid-MBBR at the
      wastewater treatment plant (WWTP) in Bad Ragaz, Switzerland was used to test the
      biotransformation. Laboratory-scale incubation experiments were performed with
      diclofenac and carriers and high-resolution LC-QTof-MS was implemented to monitor
      the biotransformation. Up to 20 diclofenac transformation products (TPs) were
      detected. Tentative structures were proposed for 16 of the TPs after
      characterization by MS2 fragmentation and/or inferring the structure from the
      transformation pathway and the molecular formula given by the high resolution
      ionic mass. The remaining four TPs were unambiguously identified via analytical
      reference standards. The postulated reactions forming the TPs were:
      hydroxylation, decarboxylation, oxidation, amide formation, ring-opening and
      reductive dechlorination. Incubation experiments of individual TPs, those which
      were available as reference standards, provided a deeper look into the
      transformation pathways. It was found that the transformation consists of four
      main pathways but no pathway accounted for a clear majority of the
      transformation. A 10-day monitoring campaign of the full-scale plant confirmed an
      88% removal of diclofenac (from approximately 1.6 MUg/L in WWTP influent) and the
      formation of TPs as found in the laboratory was observed. One of the TPs, N-(2,6
      dichlorophenyl)-2-indolinone detected at concentrations of around 0.25 MUg/L in
      WWTP effluent, accounting for 16% of the influent diclofenac concentration. The
      biotransformation of carriers was compared to a second WWTP not utilising
      carriers. It was found that in contact with activated sludge, similar
      hydroxylation and decarboxylation reactions occurred but at much slower rates,
      whereas some reactions, e.g. reductive dechlorination, were not detected at all.
      Finally, incubation experiments were performed with attached growth biomass from
      a third WWTP with a similar process configuration to Bad Ragaz WWTP. A similarly
      effective removal of diclofenac was found with a similar presence of TPs.

PMID- 27690309
TI  - Identification of Position-Specific Correlations between DNA-Binding Domains and
      Their Binding Sites. Application to the MerR Family of Transcription Factors.
AB  - The large and increasing volume of genomic data analyzed by comparative methods
      provides information about transcription factors and their binding sites that, in
      turn, enables statistical analysis of correlations between factors and sites,
      uncovering mechanisms and evolution of specific protein-DNA recognition. Here we
      present an online tool, Prot-DNA-Korr, designed to identify and analyze crucial
      protein-DNA pairs of positions in a family of transcription factors. Correlations
      are identified by analysis of mutual information between columns of protein and
      DNA alignments. The algorithm reduces the effects of common phylogenetic history
      and of abundance of closely related proteins and binding sites. We apply it to
      five closely related subfamilies of the MerR family of bacterial transcription
      factors that regulate heavy metal resistance systems. We validate the approach
      using known 3D structures of MerR-family proteins in complexes with their cognate
      DNA binding sites and demonstrate that a significant fraction of correlated
      positions indeed form specific side-chain-to-base contacts. The joint
      distribution of amino acids and nucleotides hence may be used to predict changes
      of specificity for point mutations in transcription factors.

PMID- 27690311
TI  - Knowledge about Cervical Cancer and Associated Factors among 15-49 Year Old Women
      in Dessie Town, Northeast Ethiopia.
AB  - BACKGROUND: Cervical cancer is one of the leading causes of morbidity and
      mortality amongst female cancer worldwide, especially in developing countries,
      including Ethiopia. The level of women's knowledge about cervical cancer is not
      well documented in Ethiopia. The current study sought to assess women's knowledge
      about cervical cancer and associated factors. METHODS: A community based cross
      sectional survey was conducted with a sample of 620 women aged 15-49 years
      residing in Dessie town, Northeast Ethiopia. Respondents were selected using a
      multistage sampling technique. The women were interviewed at home by trained data
      collectors using a structured questionnaire on cervical cancer knowledge.
      Knowledge about cervical cancer was measured using an eight item instrument. The
      maximum possible score was 8; those scoring 5 or more were categorized as having
      "sufficient" knowledge. Binary and multiple logistic regressions were employed to
      determine factors associated with knowledge about cervical cancer. RESULTS: A
      total of 51% of the participants had sufficient knowledge about cervical cancer.
      After adjusting for covariates, having sufficient knowledge about cervical cancer
      was positively associated with better educational level and income. Women with
      primary education (Adjusted Odds Ratio (AOR): 3.4; 95% CI: 2.2-5.1) and those who
      had secondary and above education (AOR: 8.7; 95% CI: 5.5-13.7) were more likely
      to have sufficient knowledge about cervical cancer compared to those who had no
      formal education. Furthermore, women earning an average household monthly income
      above 1500 Ethiopian birr (ETB) (~75 U.S. dollars) were more likely to have
      sufficient knowledge (AOR: 2.3; 95% CI: 1.3-3.9) than women with an average
      household monthly income less than 500 ETB (~25 U.S. dollars). CONCLUSION: This
      study shows a suboptimal knowledge about cervical cancer regarding its risk
      factors, signs and symptoms, prevention and treatment among women in the study
      site. The level of education and economic status were found to be important
      determinants for knowledge about cervical cancer. Prevention programs should
      focus cervical cancer educational resources on women with less education and
      women with lower economic status groups.

PMID- 27690312
TI  - Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac
      Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects.
AB  - Although the therapeutic effects of Vagus Nerve Stimulation (VNS) have been
      recognized in pre-clinical and pilot clinical studies, the effect of different
      stimulation configurations on the cardiovascular response is still an open
      question, especially in the case of VNS delivered synchronously with cardiac
      activity. In this paper, we propose a formal mathematical methodology to analyze
      the acute cardiac response to different VNS configurations, jointly considering
      the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube
      sampling method was chosen to design a uniform experimental plan, composed of 75
      different VNS configurations, with different values for the main parameters
      (current amplitude, number of delivered pulses, pulse width, interpulse period
      and the delay between the detected cardiac event and VNS onset). These VNS
      configurations were applied to 6 healthy, anesthetized sheep, while acquiring the
      associated cardiovascular response. Unobserved VNS configurations were estimated
      using a Gaussian process regression (GPR) model. In order to quantitatively
      analyze the effect of each parameter and their combinations on the cardiac
      response, the Sobol sensitivity method was applied to the obtained GPR model and
      inter-individual sensitivity markers were estimated using a bootstrap approach.
      Results highlight the dominant effect of pulse current, pulse width and number of
      pulses, which explain respectively 49.4%, 19.7% and 6.0% of the mean global
      cardiovascular variability provoked by VNS. More interestingly, results also
      quantify the effect of the interactions between VNS parameters. In particular,
      the interactions between current and pulse width provoke higher cardiac effects
      than the changes on the number of pulses alone (between 6 and 25% of the
      variability). Although the sensitivity of individual VNS parameters seems similar
      for chronotropic, dromotropic and inotropic responses, the interacting effects of
      VNS parameters provoke significantly different cardiac responses, showing the
      feasibility of a parameter-based functional selectivity. These results are of
      primary importance for the optimal, subject-specific definition of VNS parameters
      for a given therapy and may lead to new closed-loop methods allowing for the
      optimal adaptation of VNS therapy through time.

PMID- 27690313
TI  - Recent advancements in matrix-assisted laser desorption/ionization mass
      spectrometry imaging.
AB  - Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI)
      is a robust tool for spatially resolved analysis of biomolecules in situ. Recent
      advances in high ionization-efficiency MALDI matrices, new matrix deposition
      procedures, and the development of high spatial-resolution and high sensitivity
      MS instruments continue to drive new applications of MALDI-MSI, along with other
      MSI techniques, which allow us to visualize and determine the regio-specific and
      temporal changes in proteins, peptides, lipids, drug molecules, and metabolites
      within the tissues, cells and microorganisms. These provide researchers with a
      new route to the discovery of potential biomarkers of human disease and
      elucidation of the underlying biology of metabolic regulation, thus bringing our
      understanding of human health to a new level.

PMID- 27690316
TI  - Valley filtering by a line-defect in graphene: quantum interference and inversion
      of the filter effect.
AB  - Valley filters are crucial to any device exploiting the valley degree of freedom.
      By using an atomistic model, we analyze the mechanism leading to the valley
      filtering produced by a line-defect in graphene and show how it can be inverted
      by external means. Thanks to a mode decomposition applied to a tight-binding
      model we can resolve the different transport channels in k-space while keeping a
      simple but accurate description of the band structure, both close and further
      away from the Dirac point. This allows the understanding of a destructive
      interference effect, specifically a Fano resonance or antiresonance located on
      the p-side of the Dirac point leading to a reduced conductance. We show that in
      the neighborhood of this feature the valley filtering can be reversed by changing
      the occupations with a gate voltage, the mechanism is explained in terms of a
      valley-dependent Fano resonance splitting. Our results open the door for enhanced
      control of valley transport in graphene-based devices.

PMID- 27690315
TI  - The relationship between psoriasis and depression: A multiple mediation model.
AB  - This study examined the relationship between psoriasis and depression, proposing
      a multiple mediation model to analyse the relationship. A total of 193 patients
      with psoriasis aged 20-67 years completed the Beck Depression Inventory, the
      Stigmatization Scale, the Appearance Schemas Inventory-Revised, and the Body
      Emotions Scale. The Body Surface Area index was used to assess severity of
      psoriasis. Serial multiple mediation analysis revealed that experiences of
      stigmatization, maladaptive beliefs about appearance and its salience to one's
      self-evaluation, and negative emotional attitudes towards the body, jointly,
      sequentially mediated the relationship between the presence of skin lesions of
      psoriasis and depressive symptoms. These results highlight the importance of the
      associations between stigmatization and cognitive and affective aspects of body
      image in relation to depression in patients with psoriasis. We suggest that
      prevention and intervention programs for psoriasis patients that target body
      image enhancement would be worthy of further research.

PMID- 27690314
TI  - Widespread Shortening of 3' Untranslated Regions and Increased Exon Inclusion Are
      Evolutionarily Conserved Features of Innate Immune Responses to Infection.
AB  - The contribution of pre-mRNA processing mechanisms to the regulation of immune
      responses remains poorly studied despite emerging examples of their role as
      regulators of immune defenses. We sought to investigate the role of mRNA
      processing in the cellular responses of human macrophages to live bacterial
      infections. Here, we used mRNA sequencing to quantify gene expression and isoform
      abundances in primary macrophages from 60 individuals, before and after infection
      with Listeria monocytogenes and Salmonella typhimurium. In response to both
      bacteria we identified thousands of genes that significantly change isoform usage
      in response to infection, characterized by an overall increase in isoform
      diversity after infection. In response to both bacteria, we found global shifts
      towards (i) the inclusion of cassette exons and (ii) shorter 3' UTRs, with near
      universal shifts towards usage of more upstream polyadenylation sites. Using
      complementary data collected in non-human primates, we show that these features
      are evolutionarily conserved among primates. Following infection, we identify
      candidate RNA processing factors whose expression is associated with individual
      specific variation in isoform abundance. Finally, by profiling microRNA levels,
      we show that 3' UTRs with reduced abundance after infection are significantly
      enriched for target sites for particular miRNAs. These results suggest that the
      pervasive usage of shorter 3' UTRs is a mechanism for particular genes to evade
      repression by immune-activated miRNAs. Collectively, our results suggest that
      dynamic changes in RNA processing may play key roles in the regulation of innate
      immune responses.

PMID- 27690317
TI  - Restricted Gene Flow among Lineages of Thrips tabaci Supports Genetic Divergence
      Among Cryptic Species Groups.
AB  - Knowledge of the relative influence of population- versus species-level genetic
      variation is important to understand patterns of phenotypic variation and
      ecological relationships that exist among and within morphologically
      indistinguishable cryptic species and subspecies. In the case of cryptic species
      groups that are pests, such knowledge is also essential for devising effective
      population management strategies. The globally important crop pest Thrips tabaci
      is a taxonomically difficult group of putatively cryptic species. This study
      examines population genetic structure of T. tabaci and reproductive isolation
      among lineages of this species complex using microsatellite markers and
      mitochondrial COI sequences. Overall, genetic structure supports T. tabaci as a
      cryptic species complex, although limited interbreeding occurs between different
      clonal groups from the same lineage as well as between individuals from different
      lineages. These results also provide evidence that thelytoky and arrhenotoky are
      not fixed phenotypes among members of different T. tabaci lineages that have been
      generally associated with either reproductive mode. Possible biological and
      ecological factors contributing to these observations are discussed.

PMID- 27690318
TI  - Prevalence of diagnosed diabetes and quality of care among Greenlanders and non
      Greenlanders in Greenland.
AB  - AIMS: To estimate the actual prevalence of diagnosed diabetes in Greenland as at
      2014, and to evaluate the quality of diabetes care among Greenlanders and non
      Greenlanders in Greenland, six years after a national diabetes program was
      initiated. METHODS: The study was designed as an observational cross-sectional
      study based on review of data obtained from the electronic medical record (EMR)
      in Greenland. All permanent residents of Greenland who as at October 2014 were
      registered with the diagnosis diabetes in the EMR (n=1071) were included in the
      study. The prevalence was calculated using the population in Greenland as at
      first of June 2014 as background population. Quality of diabetes care was
      determined using indicators proposed by the Organization for Economic Cooperation
      and Development. RESULTS: The prevalence among Greenlanders aged 20-79years was
      2.36% (95% CI 2.19-2.52) and significantly lower than the prevalence among non
      Greenlanders in the same age group, which was 3.69% (95% CI 2.18-4.20). More
      Greenlanders than non-Greenlanders had glycosylated haemoglobin below 7.0%
      (53mmol/mol), blood pressure below 140/90mmHg and their blood pressure measured
      within the last year. No other differences in quality of diabetes care were
      observed between the groups. CONCLUSIONS: A higher prevalence of diagnosed
      diabetes was observed among non-Greenlanders compared to Greenlanders, while no
      major differences were observed in quality of care between the two groups. The
      overall prevalence of diagnosed diabetes has increased compared to earlier
      studies. Continued monitoring of prevalence and quality of care is recommended.

PMID- 27690319
TI  - Physical activity does not inevitably improve quality of life in young adults
      with type 1 diabetes.
AB  - Relationships between exercise, glucose control and diabetes dependent quality of
      life (DDQoL) are not straightforward. We investigated the DDQoL of 99 persons
      with type 1 diabetes and linked it to individual amount of weekly physical
      activity and HbA1c. Physically active lifestyle was not associated with better
      DDQoL or glucose control.

PMID- 27690320
TI  - Preliminary MALDI-TOF-MS analysis of seminal plasma N-glycome of infertile men.
AB  - Glycosylation pattern within reproductive tract is now suggested to be involved
      in providing female immune tolerance for allograft sperm and developing embryo,
      but the information whether impaired glycosylation may influence male fertility
      potential is still limited. We have analyzed seminal plasma N-glycome in pooled
      samples derived from fertile and infertile men by means of MALDI-TOF/TOF tandem
      mass spectrometry. Among infertile subjects, normozoospermic, oligozoospermic,
      asthenozoospermic and oligoasthenozoospermic samples were obtained. Eighty-six
      oligosaccharides were identified in all the analyzed samples. Differences in the
      content of unique glycans: high mannose and hybrid type, lacking terminal sialic
      acid and highly fucosylated were found when samples derived from infertile
      subjects with different semen patterns were compared to the fertile control. The
      content of highly branched glycans was 3-fold elevated in normozoospermic
      infertile men, while the expression of highly fucosylated oligosaccharides was
      increased in asthenozoospermic, oligozoospermic and oligoasthenozoospermic
      samples. Sialylation of oligosaccharides was decreased in oligozoospermic,
      oligoasthenozoospermic and especially asthenozoospermic samples, but increased in
      infertile normozoospermic subjects. Altered glycosylation observed in seminal
      plasma may reflect similar changes in sperm surface glycoproteins, and may
      disturb sperm interaction with female immune system. We suggest that at least
      some cases of unexplained male infertility may be associated with impaired
      glycosylation.

PMID- 27690321
TI  - The Versatile 2-Substituted Imidazoline Nucleus as a Structural Motif of Ligands
      Directed to the Serotonin 5-HT1A Receptor.
AB  - The involvement of the serotonin 5-HT1A receptor (5-HT1A -R) in the
      antidepressant effect of allyphenyline and its analogues indicates that ligands
      bearing the 2-substituted imidazoline nucleus as a structural motif interact with
      5-HT1A -R. Therefore, we examined the 5-HT1A -R profile of several imidazoline
      molecules endowed with a common scaffold consisting of an aromatic moiety linked
      to the 2-position of an imidazoline nucleus by a biatomic bridge. Our aim was to
      discover other ligands targeting 5-HT1A -R and to identify the structural
      features favoring 5-HT1A -R interaction. Structure-activity relationships,
      supported by modeling studies, suggested that some structural cliche such as a
      polar function and a methyl group in the bridge, as well as proper steric
      hindrance in the aromatic area of the above scaffold, favored 5-HT1A -R
      recognition and activation. We also highlighted the potent antidepressant-like
      effect (mouse forced swimming test) of (S)-(+)-19 [(S)-(+)-naphtyline] at very
      low dose (0.01 mg kg-1 ). This effect was clearly mediated by 5-HT1A , as it was
      significantly reduced by pretreatment with the 5-HT1A antagonist WAY100635.

PMID- 27690322
TI  - Investigation of control scans in pseudo-continuous arterial spin labeling
      (pCASL): Strategies for improving sensitivity and reliability of pCASL.
AB  - PURPOSE: To investigate the performance of control scans in pseudo-continuous ASL
      (pCASL) and propose strategies for improving sensitivity and reliability of
      pCASL. METHODS: The labeling efficiencies of pCASL with conventional control scan
      and distal control scan were investigated at various radiofrequency (RF)
      duration/spacing of 0.5/1-2/4 ms, mean slice-selection gradients (GSS ) of 1 and
      0 mT/m, and total labeling durations of 1.5-3 s, through Bloch equation
      simulations and in vivo experiments. In addition, the feasibility of three
      dimensional (3D) pCASL with the distal control scan and control scan with no RF
      preparation was demonstrated in a wide brain area, by suppressing the
      magnetization transfer (MT) effects with high GSS while maintaining the GSS /mean
      GSS ratio. RESULTS: The distal control scan provided pCASL signals approximately
      40% higher and more robust to variations in the labeling conditions than those
      from the conventional control scan. The distal and no RF control scans with high
      GSS provided uniform pCASL signals in approximately 8-cm-thick imaging region
      with MT contributions <10% of the perfusion signals. CONCLUSIONS: pCASL perfusion
      signals can be enhanced (~40%) and become more stable by using the distal or no
      RF control scan, which can be applied in a wide area by increasing GSS while
      maintaining GSS /mean GSS . Magn Reson Med 78:917-929, 2017. (c) 2016
      International Society for Magnetic Resonance in Medicine.

PMID- 27690323
TI  - Highly Luminescent Cesium Lead Halide Perovskite Nanocrystals with Tunable
      Composition and Thickness by Ultrasonication.
AB  - We describe the simple, scalable, single-step, and polar-solvent-free synthesis
      of high-quality colloidal CsPbX3 (X=Cl, Br, and I) perovskite nanocrystals (NCs)
      with tunable halide ion composition and thickness by direct ultrasonication of
      the corresponding precursor solutions in the presence of organic capping
      molecules. High angle annular dark field scanning transmission electron
      microscopy (HAADF-STEM) revealed the cubic crystal structure and surface
      termination of the NCs with atomic resolution. The NCs exhibit high
      photoluminescence quantum yields, narrow emission line widths, and considerable
      air stability. Furthermore, we investigated the quantum size effects in CsPbBr3
      and CsPbI3 nanoplatelets by tuning their thickness down to only three to six
      monolayers. The high quality of the prepared NCs (CsPbBr3 ) was confirmed by
      amplified spontaneous emission with low thresholds. The versatility of this
      synthesis approach was demonstrated by synthesizing different perovskite NCs.

PMID- 27690324
TI  - T(Rho) and magnetization transfer and INvErsion recovery (TRAMINER)-prepared
      imaging: A novel contrast-enhanced flow-independent dark-blood technique for the
      evaluation of myocardial late gadolinium enhancement in patients with myocardial
      infarction.
AB  - PURPOSE: To evaluate a new dark-blood late gadolinium enhancement (LGE) technique
      called "T(Rho) And Magnetization transfer and INvErsion Recovery" (TRAMINER) for
      the ability to detect myocardial LGE versus standard "bright-blood" inversion
      recovery (SIR) imaging. MATERIALS AND METHODS: This Institutional Review Board
      (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)
      compliant prospective study included 40 patients (62 +/- 14 years [mean +/-
      standard deviation (SD)], 29 males) with suspected myocardial infarction (MI)
      referred for the assessment of myocardial viability. The patients underwent a
      1.5T cardiac magnetic resonance imaging (MRI) including postcontrast SIR and
      TRAMINER acquisitions. Normalized images were evaluated by two readers.
      Subjective (3-point Likert scale) and objective image qualities were compared
      using Mann-Whitney U-test and paired t-test, respectively. Interobserver
      agreement, LGE detection rate, and level of certainty were compared using Cohen's
      kappa, Wilcoxon-test, and Mann-Whitney U-test, respectively. Results are reported
      as mean +/- SD or mean [95% confidence interval]. RESULTS: Overall, image quality
      was rated similar between TRAMINER and SIR; however, TRAMINER performed better on
      a visual assessment of the ability to differentiate LGE from blood (Likert scale:
      3.0 [3.0-3.0] vs. 2.0 [1.7-2.2], P < 0.0001). TRAMINER provided significantly
      higher signal intensity range (69.8 +/- 10.2 vs. 9.6 +/- 7.6, P < 0.0001) and a 4
      fold higher signal intensity ratio (4.2 +/- 1.9 vs. 1.1 +/- 0.1, P < 0.0001)
      between LGE and blood signals. TRAMINER detected more patients (19/40 vs. 17/40)
      and segments (91/649 vs. 79/649) with LGE with higher level of certainty (2.9
      [2.8-3.0] vs. 2.7 [2.5-2.8], P = 0.0185). Interobserver agreement was good to
      excellent for LGE detection. CONCLUSION: TRAMINER provides better contrast
      between LGE and blood and consequently may have increased ability to discriminate
      thin subendocardial and papillary muscle enhancement from the blood signal, which
      can have an indistinct appearance using SIR. LEVEL OF EVIDENCE: 2 J. MAGN. RESON.
      IMAGING 2017;45:1429-1437.

PMID- 27690325
TI  - Biotransformation of cholesterol and 16,17-alpha epoxypregnenolone by novel
      Cladosporium sp. strain IS547.
AB  - Nowadays, there are a few steroid drugs or intermediates that have been obtained
      via the transformation of microorganisms, and many strains of transformed
      steroids have not been found yet. Therefore, it is very significant to screen for
      the strains that have the abilities to transform steroids to produce valuable
      products. This study has focused on the screen and identification of strains, the
      structural identification of converted products, and the optimization of
      transformation conditions, as well as the establishment of transformation
      systems. A soil microbiota was screened for strain involved in the
      biotransformation of steroids. A new isolate IS547 is capable of converting a
      variety of steroids (such as cholesterol, ergosterol, hydrocortisone,
      progesterone, pregnenolone, and 16,17-alpha-epoxypregnenolone). Based on the 18S
      rDNA gene sequence comparison, the isolate IS547 has been demonstrated to be very
      closely related to Cladosporium sp. genus. Present paper is the first report
      regarding the microbial transformation by Cladosporium sp. to produce active
      intermediates, which include 7-hydroxy cholesterol, 20-droxyl-16alpha,17alpha
      epoxypregna-4-dien-3-one, 7-ketocholesterol, and 7-droxyl-16alpha,17alpha
      epoxypregna-4-dien-3,20-dione. Under the optimum conditions, the yields of
      product 3 and product 4 were 20.58 and 17.42%, respectively, higher than that
      prior to the optimization. The transformation rate increased significantly under
      the optimum fermentation conditions. This study describes an efficient, rapid,
      and inexpensive biotransformation system for the production of active
      pharmaceutical intermediates.

PMID- 27690326
TI  - Analysis of the complete plastomes of three species of Membranoptera (Ceramiales,
      Rhodophyta) from Pacific North America.
AB  - Next generation sequence data were generated and used to assemble the complete
      plastomes of the holotype of Membranoptera weeksiae, the neotype (designated
      here) of M. tenuis, and a specimen examined by Kylin in making the new
      combination M. platyphylla. The three plastomes were similar in gene content and
      length and showed high gene synteny to Calliarthron, Grateloupia, Sporolithon,
      and Vertebrata. Sequence variation in the plastome coding regions were 0.89%
      between M. weeksiae and M. tenuis, 5.14% between M. weeksiae and M. platyphylla,
      and 5.18% between M. tenuis and M. platyphylla. We were unable to decipher the
      complete mitogenomes of the three species due to low coverage and structural
      problems; however, we assembled and analyzed, the cytochrome oxidase I, II, and
      III loci and found that M. weeksiae and M. tenuis differed in sequence by 1.3%,
      M. weeksiae and M. platyphylla by 8.4%, and M. tenuis and M. platyphylla by 8.1%.
      Evaluation of standard marker genes indicated that sequences from the rbcL,
      RuBisCO spacer, and CO1 genes closely approximated the pair-wise genetic
      distances observed between the plastomes of the three species of Membranoptera. A
      phylogenetic tree based on rbcL sequences showed that M. tenuis and M. weeksiae
      were sister taxa. Short rbcL sequences were obtained from type specimens of M.
      dimorpha, M. multiramosa, and M. edentata and confirmed their conspecificity with
      M. platyphylla. The data support the recognition of three species of
      Membranoptera occurring south of Alaska: M. platyphylla, M. tenuis, and M.
      weeksiae.

PMID- 27690327
TI  - Tetraarylethylenes from Diarylmethanones and Hexachlorodisilane: The "Sila
      McMurry" Reaction.
AB  - Hexachlorodisilane reacts with diarylmethanones (aryl=C6 H5 , 4-MeC6 H4 , 4-tBuC6
      H4 , 4-ClC6 H4 , 4-BrC6 H4 ) to furnish the corresponding tetraarylethylenes in
      good yields. The reductive conversion requires temperatures of about 160  degrees
      C and reaction times of 60-72 h. In the initial step, the Lewis-basic carbonyl
      groups likely generate low-valent [SiCl2 ] as an analogue of [TiCl2 ] in the
      classical McMurry reaction. The coupling sequence further proceeds via
      benzopinacolones, which have been isolated as key intermediates.

PMID- 27690328
TI  - The convergence of senescence and nutrient sensing during lymphocyte ageing.
AB  - Immunosurveillance requires the migration of lymphocytes and their activation to
      induce proliferation and effector function. Effective immunity requires an
      optimal supply of nutrients to lymphocytes. Cells contain nutrient sensing
      apparatus such as adenosine 5'-monophosphate-activated protein kinase (AMPK) that
      surveys intracellular ATP levels. Immunity declines during ageing and one
      possibility is that the energy balance may be altered in old lymphocytes. This
      paper summarizes recent data identifying a convergence of senescence and nutrient
      signalling pathways in lymphocytes that inhibit both T cell and natural killer
      (NK) cell function during ageing. Significantly, these pathways can be inhibited
      to enhance the activity of these cells.

PMID- 27690329
TI  - Real-Time Label-Free Monitoring of Nanoparticle Cell Uptake.
AB  - The surface plasmon resonance technique in combination with whole cell sensing is
      used for the first time for real-time label-free monitoring of nanoparticle cell
      uptake. The uptake kinetics of several types of nanoparticles relevant to drug
      delivery applications into HeLa cells is determined. The cell uptake of the
      nanoparticles is confirmed by confocal microscopy. The cell uptake of silica
      nanoparticles and polyethylenimine-plasmid DNA polyplexes is studied as a
      function of temperature, and the uptake energies are determined by Arrhenius
      plots. The phase transition temperature of the HeLa cell membrane is detected
      when monitoring cell uptake of silica nanoparticles at different temperatures.
      The HeLa cell uptake of the mesoporous silica nanoparticles is energy-independent
      at temperatures slightly higher than the phase transition temperature of the HeLa
      cell membrane, while the uptake of polyethylenimine-DNA polyplexes is energy
      dependent and linear as a function of temperature with an activation energy of Ea
      = 62 +/- 7 kJ mol-1 = 15 +/- 2 kcal mol-1 . The HeLa cell uptake of red blood
      cell derived extracellular vesicles is also studied as a function of the
      extracellular vesicle concentration. The results show a concentration dependent
      behavior reaching a saturation level of the extracellular vesicle uptake by HeLa
      cells.

PMID- 27690330
TI  - Mapping of a FEB3 homologous febrile seizure locus on mouse chromosome 2
      containing candidate genes Scn1a and Scn3a.
AB  - Febrile seizures (FS) are the most common seizure type in children. Recurrent FS
      are a risk factor for developing temporal lobe epilepsy later in life and are
      known to have a strong genetic component. Experimental FS (eFS) can be elicited
      in mice by warm-air induced hyperthermia. We used this model to screen the
      chromosome substitution strain (CSS) panel derived from C57BL/6J and A/J for FS
      susceptibility and identified C57BL/6J-Chr2A /NaJ (CSS2), as the strain with the
      strongest FS susceptibility phenotype. The aim of this study was to map FS
      susceptibility loci and select candidate genes on mouse chromosome 2. We
      generated an F2 population by intercrossing the hybrids (F1 ) that were derived
      from CSS2 and C57BL/6J mice. All CSS2-F2 individuals were genotyped and
      phenotyped for eFS susceptibility, and QTL analysis was performed. Candidate gene
      selection was based on bioinformatics analyses and differential brain expression
      between CSS2 and C57BL/6J strains determined by microarray analysis. Genetic
      mapping of the eFS susceptibility trait identified two significant loci: FS-QTL2a
      (LOD-score 3.6) and FS-QTL2b (LOD-score 6.2). FS-QTL2a contained 44 genes
      expressed in the brain at post natal day 14. Four of these (Arl6ip6, Cytip, Fmnl2
      Ifih1) contained a non-synonymous SNP comparing CSS2 and C57BL/6J, six genes
      (March7, Nr4a2, Gpd2, Grb14, Scn1a, Scn3a) were differentially expressed between
      these strains. A region within FS-QTL2a is homologous to the human FEB3 locus.
      The fact that we identify mouse FS-QTL2a with high FEB3 homology is strong
      support for the validity of the eFS mouse model to study genetics of human FS.

PMID- 27690331
TI  - Could metformin be used in patients with diabetes and advanced chronic kidney
      disease?
AB  - Diabetes is an important cause of end stage renal failure worldwide. As renal
      impairment progresses, managing hyperglycaemia can prove increasingly
      challenging, as many medications are contra-indicated in moderate to severe renal
      impairment. Whilst evidence for tight glycaemic control reducing progression to
      renal failure in patients with established renal disease is limited, poor
      glycaemic control is not desirable, and is likely to lead to progressive
      complications. Metformin is a first-line therapy in patients with Type 2
      diabetes, as it appears to be effective in reducing diabetes related end points
      and mortality in overweight patients. Cessation of metformin in patients with
      progressive renal disease may not only lead to deterioration in glucose control,
      but also to loss of protection from cardiovascular disease in a cohort of
      patients at particularly high risk. We advocate the need for further study to
      determine the role of metformin in patients with severe renal disease (chronic
      kidney disease stage 4-5), as well as patients on dialysis, or pre-/peri-renal
      transplantation. We explore possible roles of metformin in these circumstances,
      and suggest potential key areas for further study.

PMID- 27690332
TI  - Validation and application of a nondestructive and contactless method for
      rheological evaluation of biomaterials.
AB  - Hydrogels are extensively used for tissue engineering, cell therapy or controlled
      release of bioactive factors. Nondestructive techniques that can follow their
      viscoelastic properties during polymerization, remodeling, and degradation are
      needed, since these properties are determinant for their in vivo efficiency. In
      this work, we proposed the viscoelastic testing of bilayered materials (VeTBiM)
      as a new method for nondestructive and contact-less mechanical characterization
      of soft materials. The VeTBiM method measures the dynamic displacement response
      of a material, to a low amplitude vibration in order to characterize its
      viscoelastic properties. We validated VeTBiM by comparing data obtained on
      various agar and chitosan hydrogels with data from rotational rheometry, and
      compression tests. We then investigated its potential to follow the mechanical
      properties of chitosan hydrogels during gelation and in the presence of papain
      and lysozyme that induce fast or slow enzymatic degradation. Due to this
      nondestructive and contactless approach, samples can be removed from the
      instrument and stored in different conditions between measurements. VeTBiM is
      well adapted to follow biomaterials alone or with cells, over long periods of
      time. This new method will help in the fine tuning of the mechanical properties
      of biomaterials used for cell therapy and tissue engineering. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2565-2573,
      2017.

PMID- 27690333
TI  - A Highly Efficient and Self-Stabilizing Metallic-Glass Catalyst for
      Electrochemical Hydrogen Generation.
AB  - A multicomponent metallic glass (MG) with highly efficient and anomalous
      durability for catalyzing water splitting is reported. The outstanding
      performance of the MG catalyst contributed by self-optimized active sites
      originates from the intrinsic chemical heterogeneity and selective dealloying on
      the disordered surface; thus, a new mechanism for improving the durability of
      catalysts is uncovered.

PMID- 27690334
TI  - Human umbilical cord derivatives regenerate intervertebral disc.
AB  - Intervertebral disc (IVD) degeneration is characterized by the loss of nucleus
      pulposus (NP), which is a common cause for lower back pain. Although, currently,
      there is no cure for the degenerative disc disease, stem cell therapy is
      increasingly being considered for its treatment. In this study, we investigated
      the feasibility and efficacy of human umbilical cord mesenchymal stem cells
      (MSCs) and chondroprogenitor cells (CPCs) derived from those cells to regenerate
      damaged IVD in a rabbit model. Transplanted cells survived, engrafted and
      dispersed into NP in situ. Significant improvement in the histology, cellularity,
      extracellular matrix proteins, and water and glycosaminoglycan contents in IVD
      recipients of CPCs was observed compared to MSCs. In addition, IVDs receiving
      CPCs exhibited higher expression of NP-specific human markers, SOX9, aggrecan,
      collagen 2, FOXF1 and KRT19. The novelty of the study is that in vitro
      differentiated CPCs derived from umbilical cord MSCs, demonstrated far greater
      capacity to regenerate damaged IVDs, which provides basis and impetus for stem
      cell based clinical studies to treat degenerative disc disease. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27690335
TI  - Tuning Nanowires and Nanotubes for Efficient Fuel-Cell Electrocatalysis.
AB  - Developing new synthetic methods for the controlled synthesis of Pt-based or non
      Pt nanocatalysts with low or no Pt loading to facilitate sluggish cathodic oxygen
      reduction reaction (ORR) and organics oxidation reactions is the key in the
      development of fuel-cell technology. Various nanoparticles (NPs), with a range of
      size, shape, composition, and structure, have shown good potential to catalyze
      the sluggish cathodic and anodic reactions. In contrast to NPs, one-dimensional
      (1D) nanomaterials such as nanowires (NWs), and nanotubes (NTs), exhibit
      additional advantages associated with their anisotropy, unique structure, and
      surface properties. The prominent characteristics of NWs and NTs include fewer
      lattice boundaries, a lower number of surface defect sites, and easier electron
      and mass transport for better electrocatalytic activity and lower vulnerability
      to dissolution, Ostwald ripening, and aggregation than Pt NPs for enhanced
      stability. An overview of recent advances in tuning 1D nanostructured Pt-based,
      Pd-based, or 1D metal-free nanomaterials as advanced electrocatalysts is provided
      here, for boosting fuel-cell reactions with high activity and stability,
      including the oxygen reduction reaction (ORR), methanol oxidation reaction (MOR),
      and ethanol oxidation reaction (EOR). After highlighting the different strategies
      developed so far for the synthesis of Pt-based 1D nanomaterials with controlled
      size, shape, and composition, special emphasis is placed on the rational design
      of diverse NWs and NTs catalysts such as Pt-based NWs or NTs, non-Pt NTs, and
      carbon NTs with molecular engineering, etc. for enhancing the ORR, MOR, and EOR.
      Finally, some perspectives are highlighted on the development of more efficient
      fuel-cell electrocatalysts featuring high stability, low cost, and enhanced
      performance, which are the key factors in accelerating the commercialization of
      fuel-cell technology.

PMID- 27690336
TI  - Bioprocess development workflow: Transferable physiological knowledge instead of
      technological correlations.
AB  - Microbial bioprocesses need to be designed to be transferable from lab scale to
      production scale as well as between setups. Although substantial effort is
      invested to control technological parameters, usually the only true constant
      parameter is the actual producer of the product: the cell. Hence, instead of
      solely controlling technological process parameters, the focus should be
      increasingly laid on physiological parameters. This contribution aims at
      illustrating a workflow of data life cycle management with special focus on
      physiology. Information processing condenses the data into physiological
      variables, while information mining condenses the variables further into
      physiological descriptors. This basis facilitates data analysis for a
      physiological explanation for observed phenomena in productivity. Targeting
      transferability, we demonstrate this workflow using an industrially relevant
      Escherichia coli process for recombinant protein production and substantiate the
      following three points: (1) The postinduction phase is independent in terms of
      productivity and physiology from the preinduction variables specific growth rate
      and biomass at induction. (2) The specific substrate uptake rate during induction
      phase was found to significantly impact the maximum specific product titer. (3)
      The time point of maximum specific titer can be predicted by an easy accessible
      physiological variable: while the maximum specific titers were reached at
      different time points (19.8 +/- 7.6 h), those maxima were reached all within a
      very narrow window of cumulatively consumed substrate dSn (3.1 +/- 0.3 g/g).
      Concluding, this contribution provides a workflow on how to gain a physiological
      view on the process and illustrates potential benefits. (c) 2016 American
      Institute of Chemical Engineers Biotechnol. Prog., 33:261-270, 2017.

PMID- 27690337
TI  - Determination of sex from the patella in a contemporary Spanish population.
AB  - The skull and pelvis have been used for the determination of sex for unknown
      human remains. However, in forensic cases where skeletal remains often exhibit
      postmortem damage and taphonomic changes the patella may be used for the
      determination of sex as it is a preservationally favoured bone. The goal of the
      present research was to derive discriminant function equations from the patella
      for estimation of sex from a contemporary Spanish population. Six parameters were
      measured on 106 individuals (55 males and 51 females), ranging in age from 22 to
      85 years old, from the Granada Osteological Collection. The statistical analyses
      showed that all variables were sexually dimorphic. Discriminant function score
      equations were generated for use in sex determination. The overall accuracy of
      sex classification ranged from 75.2% to 84.8% for the direct method and 75.5%
      83.8% for the stepwise method. When the South African White discriminant
      functions were applied to the Spanish sample they showed high accuracy rates for
      sexing female patellae (90%-95.9%) and low accuracy rates for sexing male
      patellae (52.7%-58.2%). When the South African Black discriminant functions were
      applied to the Spanish sample they showed high accuracy rates for sexing male
      patellae (90.9%) and low accuracy rates for sexing female patellae (70%-75.5%).
      The patella was shown to be useful for sex determination in the contemporary
      Spanish population.

PMID- 27690338
TI  - Cardiovascular pharmacotherapy.

PMID- 27690339
TI  - Echo and natriuretic peptide guided therapy improves outcome and reduces
      worsening renal function in systolic heart failure: An observational study of
      1137 outpatients.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) and echocardiography are potentially
      useful adjunct to guide management of patients with chronic heart failure
      (HF).Thus, the aim of this retrospective, multicenter study was to compare
      outcomes and renal function in outpatients with chronic HF with reduced ejection
      fraction (HFrEF) who underwent an echo and BNP guided or a clinically driven
      protocol for follow-up. METHODS AND RESULTS: In 1137 consecutive outpatients,
      management was guided according to echo-Doppler signs of elevated left
      ventricular filling pressure and BNP levels conforming to the protocol of the
      Network Labs Ultrasound (NEBULA) in HF Study Group in 570 (mean EF=30%), while
      management was clinically driven based on the institutional protocol of the HF
      Unit of the Cardiovascular and Thoracic Department in 567 (mean EF=33%).
      Propensity score, matching several confounding baseline variables, was used to
      match pairs based on treatment strategy. The median follow-up was 37.4months.
      After propensity matching, a lower incidence of death (HR 0.45, 95%CI: 0.30-0.67,
      p<0.0001), and death or worsening renal function (HR 0.49, 95%CI 0.36-0.67,
      p<0.0001) was apparent in echo-BNP-guided group compared to clinically-guided
      group. Worsening of renal function (>=0.3mg/dl increase in serum creatinine) was
      observed in 9.8% of echo-BNP-guided group and in 21.4% of clinical assessed group
      (p<0.0001). The daily dose of loop diuretics did not change in echo-BNP-guided
      group, while it increased in 65% of patients in clinically-guided group
      (p<0.0001). CONCLUSIONS: Echo and BNP guided management may improve the outcome
      and reduce worsening of renal function in outpatients with chronic HFrEF.

PMID- 27690340
TI  - Gastrointestinal complications associated with catheter ablation for atrial
      fibrillation.
AB  - Atrial fibrillation is the most common arrhythmia in the United States. With the
      ageing population, the incidence and prevalence of atrial fibrillation are on the
      rise. Catheter ablation of atrial fibrillation is a widely accepted treatment
      modality in patients with drug refractory symptomatic paroxysmal or persistent
      atrial fibrillation. The close proximity to the left atrium posterior wall makes
      the thermosensitive esophagus a potential site of injury during catheter ablation
      of AF leading to various gastrointestinal complications. The major
      gastrointestinal complications associated with catheter ablation include
      atrioesophageal fistula, gastroparesis, esophageal thermal lesions and esophageal
      ulcers. Multiple studies, case reports and series have described these
      complications with various catheter ablation techniques such as radiofrequency,
      cryoenergy and high frequency focused ultrasound energy ablation. This review
      addresses the gastrointestinal complications after AF ablation procedures and
      aims to provide the clinicians with an overview of clinical presentation,
      etiology, pathogenesis, prevention and management of these conditions.

PMID- 27690341
TI  - Hormonal receptors in lung adenocarcinoma: expression and difference in outcome
      by sex.
AB  - BACKGROUND: Lung cancer seems to have different epidemiological, biomolecular and
      clinical characteristics in females than in males, with a better prognosis for
      women. The aim of the study is to determine gender differences in lung
      adenocarcinoma in terms of androgen (AR), estrogen (ER)alpha and progesterone
      (PgR) receptors expression and their impact on outcome. RESULTS: Overall survival
      was significantly better in ERalpha and in PgR positive lung adenocarcinoma
      patients (median survival 45 vs. 19 months).Eight out of 62 patients showed
      positive expression of nuclear (n) AR and 18 of cytoplasmic (c) AR with a
      significantly better survival (49 vs. 19 and 45 vs. 19 months, respectively).
      There was a significant difference in survival between patients with vs. without
      c-AR expression (30 vs. 17 months). Finally, in the subgroup of women, median
      survival was greater in positive expression of c-AR than for women with negative
      c-AR (45 vs. 21 months). MATERIALS AND METHODS: We conducted an analysis on a
      cohort of 62 patients with advanced NSCLC treated at our institution. We
      investigated the immunohistochemical expression of n/c AR, ERalpha and PgR in 62
      NSCLC and we correlated it with patients' clinic-pathologic characteristics and
      with prognosis. CONCLUSIONS: Our results showed that the positive expression of
      one hormonal receptor could represent a prognostic factor.Furthermore our study
      suggests that AR should become object of close examination in a larger series of
      lung adenocarcinoma patients, also for selection of the patients with best
      prognosis that can perform more chemotherapy lines.

PMID- 27690342
TI  - Tyrosine kinase LYN is an oncotarget in human cervical cancer: A quantitative
      proteomic based study.
AB  - Cervical cancer is one of the most common malignant tumor in women. The
      mechanisms of cervical cancer are intricate and have not been fully understood.
      Therefore, we employed iTRAQ to obtain novel proteins profile which participates
      in the tumor oncogenesis of cervical cancer. 3300 proteins were identified
      aberrantly expressed in cervical cancer, and western bolt was performed to
      validate the results of iTRAQ. Then, we selected LYN for further study.
      Immunohistochemistry identified that LYN expression was significantly increased
      in cervical cancer tissues than that in cancer adjacent normal cervical tissues
      and normal cervical tissues. The increased LYN expression was significantly
      correlated with cancer differentiation and FIGO stage. Silencing LYN inhibited
      cell proliferation, migration and invasion, conversely, overexpression LYN
      promoted cell proliferation, migration and invasion. In terms of mechanism, LYN
      could also promote cervical cancer cells metastasis through activating IL-6/STAT3
      pathway. In vivo study, overexpression LYN promoted tumor growth, meanwhile
      knockdown LYN inhibited tumor growth. These results indicate that LYN tyrosine
      kinase is an oncogenic gene and can serve as a novel target for cervical cancer
      research and therapy.

PMID- 27690343
TI  - Should all breast cancer patients with four or more positive lymph nodes who
      underwent modified radical mastectomy be treated with postoperative radiotherapy?
      A population-based study.
AB  - Postmastectomy radiotherapy (PMRT) has become a standard adjuvant postoperative
      therapy for breast cancer patients with four or more positive lymph nodes.
      However, some studies have demonstrated that some subgroups of the breast cancer
      patients with four or more positive lymph nodes did not benefit substantially
      from PMRT. Therefore, it is of great necessity to identify whether all breast
      cancer patients with four or more positive lymph nodes who underwent modified
      radical mastectomy be treated with PMRT. In our study, we first established a
      prognostic model using the Surveillance Epidemiology and End Results (SEER)
      database between 1998 and 2001. Univariate and multivariate Cox models were used
      to assess the prognostic factors, and five risk factors individually associated
      with prognosis including AJCC stage, AJCC T, Grade, ER status, PR status.
      Prognostic index of PMRT were defined as the number of risk factor (NRF). The NRF
      scores correlated well with overall survival of PMRT even if the patients were in
      the sub-poor prognosis group. Then the prognostic model was validated using the
      SEER database between 2006 and 2009, and the same results were obtained. In
      conclusion, different from others studies, our study demonstrated that all
      patients with four or more positive lymph nodes after modified radical mastectomy
      need to be treated with PMRT ever if the patients belonged to AJCC T4 in a poor
      prognosis group.

PMID- 27690344
TI  - The effect of the severity of obstructive sleep apnea syndrome on telomere
      length.
AB  - Aging is associated with an increase in the prevalence of obstructive sleep apnea
      syndrome (OSAS) as well as the shortening of telomeres. It is known that OSAS
      related factors are stimuli that can contribute to the acceleration of cellular
      senescence. Thus, the present study aimed to compare the leukocyte telomere
      length (LTL) between OSAS patients and controls, as well as to verify the
      correlation between LTL and sleep parameters. We used DNA extracted of 928
      individuals from EPISONO to measure the LTL by the quantitative real-time
      polymerase chain reaction. All individuals were subjected to one full-night
      polysomnography. LTL was significantly shorter in OSAS patients compared to
      controls. The results showed negative correlations between LTL and the following
      variables: apnea-hypopnea index, respiratory disturbance index, desaturation
      index and wake after sleep onset. LTL was positively correlated with sleep
      efficiency, total sleep time, basal, minimum and maximum oxygen saturation.
      Lastly, it was observed that OSAS severity was associated with shorter LTL even
      after adjusting for sex, age, years of schooling, body mass index, diabetes,
      stroke and heart attack. In conclusion, our study indicates the presence of an
      association between LTL and OSAS and a significant impact of severity of OSAS in
      telomeres shortening.

PMID- 27690346
TI  - Preventing probe induced topography correlated artifacts in Kelvin Probe Force
      Microscopy.
AB  - Kelvin Probe Force Microscopy (KPFM) on samples with rough surface topography can
      be hindered by topography correlated artifacts. We show that, with the proper
      experimental configuration and using homogeneously metal coated probes, we are
      able to obtain amplitude modulation (AM) KPFM results on a gold coated sample
      with rough topography that are free from such artifacts. By inducing tip
      inhomogeneity through contact with the sample, clear potential variations appear
      in the KPFM image, which correlate with the surface topography and, thus, are
      probe induced artifacts. We find that switching to frequency modulation (FM) KPFM
      with such altered probes does not remove these artifacts. We also find that the
      induced tip inhomogeneity causes a lift height dependence of the KPFM
      measurement, which can therefore be used as a check for the presence of probe
      induced topography correlated artifacts. We attribute the observed effects to a
      work function difference between the tip and the rest of the probe and describe a
      model for such inhomogeneous probes that predicts lift height dependence and
      topography correlated artifacts for both AM and FM-KPFM methods. This work
      demonstrates that using a probe with a homogeneous work function and preventing
      tip changes is essential for KPFM on non-flat samples. From the three
      investigated probe coatings, PtIr, Au and TiN, the latter appears to be the most
      suitable, because of its better resistance against coating damage.

PMID- 27690345
TI  - Comparative effectiveness of combined therapy inhibiting EGFR and VEGF pathways
      in patients with advanced non-small-cell lung cancer: a meta-analysis of 16 phase
      II/III randomized trials.
AB  - BACKGROUND & AIMS: Combined therapy inhibiting EGFR and VEGF pathways is becoming
      a promising therapy in the treatment of advanced non-small-cell lung cancer
      (NSCLC), however, with controversy. The study aims to compare the efficacy of
      combined inhibition therapy versus control therapy (including placebo, single
      EGFR inhibition and single VEGF inhibition) in patients with advanced NSCLC.
      MATERIALS AND METHODS: An adequate literature search in EMBASE, Cochrane Central
      Register of Controlled Trials (CENTRAL), American Society of Clinical Oncology
      (ASCO) and European Society of Medical Oncology (ESMO) was conducted. Phase II or
      III randomized controlled trials (RCTs) that compared effectiveness between
      combined inhibition therapy and control therapy in patients with advanced NSCLC
      were eligible. The endpoint was overall response rate (ORR), progression free
      survival (PFS) and overall survival (OS). RESULTS: Sixteen phase II or III RCTs
      involving a total of 7,109 patients were included. The results indicated that the
      combined inhibition therapy significantly increased the ORR (OR = 1.59, 95% CI =
      1.36-1.87, p<0.00001; I2 = 36%) when compared to control therapy. In the subgroup
      analysis, the combined inhibition therapy clearly increased the ORR (OR = 2.04,
      95% CI = 1.60-2.60, p<0.00001; I2 = 0%) and improved the PFS (HR = 0.78, 95% CI =
      0.71-0.85, p<0.00001;I2 = 0%) when compared with the placebo, and similar results
      was detected when compared with the single EGFR inhibition in terms of ORR (OR =
      1.39, 95% CI = 1.12-1.74, p = 0.003; I2 = 30%) and PFS (HR = 0.73, 95% CI = 0.67
      0.81, p<0.0001; I2 = 50%). No obvious difference was found between the combined
      inhibition therapy and single VEGF inhibition in term of ORR, however, combined
      inhibition therapy significantly decreased the PFS when compared to the single
      VEGF inhibition therapy (HR = 1.70, 95% CI = 1.34-2.17, p<0.0001; I2 = 50%).
      Besides, no significant difference was observed between the combined inhibition
      therapy and control therapy in term of OS (including placebo, single EGFR
      inhibition and single VEGF inhibition) (HR = 0.98, 95% CI = 0.92-1.04, p = 0.41;
      I2 = 0%). CONCLUSIONS: Combined inhibition therapy was superior to placebo and
      single EGFR inhibition in terms of ORR, PFS for advanced NSCLC, however, no
      statistical difference were found in term of OS. Besides, combined inhibition
      therapy was not superior to single VEGF inhibition in terms of ORR, PFS and OS.
      Therefore, combined inhibition therapy is recommended to treat advanced NSCLC
      patients.

PMID- 27690347
TI  - Dark-field image contrast in transmission scanning electron microscopy: Effects
      of substrate thickness and detector collection angle.
AB  - An annular dark field (ADF) detector was placed beneath a specimen in a field
      emission scanning electron microscope operated at 30kV to calibrate detector
      response to incident beam current, and to create transmission images of gold
      nanoparticles on silicon nitride (SiN) substrates of various thicknesses. Based
      on the linear response of the ADF detector diodes to beam current, we developed a
      method that allowed for direct determination of the percentage of that beam
      current forward scattered to the ADF detector from the sample, i.e. the
      transmitted electron (TE) yield. Collection angles for the ADF detector region
      were defined using a masking aperture above the detector and were systematically
      varied by changing the sample to detector distance. We found the contrast of the
      nanoparticles, relative to the SiN substrate, decreased monotonically with
      decreasing inner exclusion angle and increasing substrate thickness. We also
      performed Monte Carlo electron scattering simulations, which showed quantitative
      agreement with experimental contrast associated with the nanoparticles. Together,
      the experiments and Monte Carlo simulations revealed that the decrease in
      contrast with decreasing inner exclusion angle was due to a rapid increase in the
      TE yield of the low atomic number substrate. Nanoparticles imaged at low inner
      exclusion angles (<150mrad) and on thick substrates (>50nm) showed low image
      contrast in their centers surrounded by a bright high-contrast halo on their
      edges. This complex image contrast was predicted by Monte Carlo simulations,
      which we interpreted in terms of mixing of the nominally bright field (BF) and
      ADF electron signals. Our systematic investigation of inner exclusion angle and
      substrate thickness effects on ADF t-SEM imaging provides fundamental
      understanding of the contrast mechanisms for image formation, which in turn
      suggest practical limitations and optimal imaging conditions for different
      substrate thicknesses.

PMID- 27690348
TI  - EBSD spatial resolution for detecting sigma phase in steels.
AB  - The spatial resolution of the electron backscatter diffraction signal is explored
      by Monte Carlo simulation for the sigma phase in steel at a typical instrumental
      set-up. In order to estimate the active volume corresponding to the diffracted
      electrons, the fraction of the backscattered electrons contributing to the
      diffraction signal was inferred by extrapolating the Kikuchi pattern contrast
      measured by other authors, as a function of the diffracted electron energy. In
      the resulting estimation, the contribution of the intrinsic incident beam size
      and the software capability to deconvolve patterns were included. A strong
      influence of the beam size on the lateral resolution was observed, resulting in
      20nm for the aperture considered. For longitudinal and depth directions the
      resolutions obtained were 75nm and 16nm, respectively. The reliability of this
      last result is discussed in terms of the survey of the last large-angle
      deflection undergone by the backscattered electrons involved in the diffraction
      process. Bearing in mind the mean transversal resolution found, it was possible
      to detect small area grains of sigma phase by EBSD measurements, for a stabilized
      austenitic AISI 347 stainless steel under heat treatments, simulating post
      welding (40h at 600 degrees C) and aging (284h at 484 degrees C) effects-as
      usually occurring in nuclear reactor pressure vessels.

PMID- 27690349
TI  - Nonlinear Hebbian Learning as a Unifying Principle in Receptive Field Formation.
AB  - The development of sensory receptive fields has been modeled in the past by a
      variety of models including normative models such as sparse coding or independent
      component analysis and bottom-up models such as spike-timing dependent plasticity
      or the Bienenstock-Cooper-Munro model of synaptic plasticity. Here we show that
      the above variety of approaches can all be unified into a single common
      principle, namely nonlinear Hebbian learning. When nonlinear Hebbian learning is
      applied to natural images, receptive field shapes were strongly constrained by
      the input statistics and preprocessing, but exhibited only modest variation
      across different choices of nonlinearities in neuron models or synaptic
      plasticity rules. Neither overcompleteness nor sparse network activity are
      necessary for the development of localized receptive fields. The analysis of
      alternative sensory modalities such as auditory models or V2 development lead to
      the same conclusions. In all examples, receptive fields can be predicted a priori
      by reformulating an abstract model as nonlinear Hebbian learning. Thus nonlinear
      Hebbian learning and natural statistics can account for many aspects of receptive
      field formation across models and sensory modalities.

PMID- 27690350
TI  - Mothers and fathers of young Dutch adolescents with Down syndrome: Health related
      quality of life and family functioning.
AB  - BACKGROUND: Like any child, children with Down syndrome (DS) affect the lives of
      their families. Most studies focus on the adaptation of parents and families of
      young children with DS, while relatively few studies include the perspective of
      fathers. AIMS: To determine 1) whether mothers and fathers of 11 to 13-year-olds
      with DS differ from reference parents in health related quality of life (HRQoL)
      and family functioning, and 2) whether HRQoL in parents of children with DS
      changes over time, from when the child was 6-8 years old to when the child was 11
      13 years old. METHODS: 80 mothers and 44 fathers completed HRQoL and family
      functioning questionnaires. 58 parents (53 mothers) had completed the HRQoL
      questionnaire in a previous study. RESULTS: Mothers differed from reference
      mothers in one HRQoL-domain (Sexuality), while fathers' HRQoL did not
      significantly differ from reference fathers. Both mothers and fathers scored in
      the (sub)clinical range more frequently than reference parents in Total family
      functioning, and in the domains Partner relation and Social network. Furthermore,
      fathers scored in the (sub)clinical range more frequently than reference parents
      in Responsiveness and Organization. HRQoL showed no significant change over time.
      CONCLUSIONS AND IMPLICATIONS: Our findings indicate frequent family functioning
      problems but few HRQoL problems in parents and families of children with DS. In
      offering care, a family based approach with special attention for partner
      relation and social functioning is needed.

PMID- 27690351
TI  - Disrupted latent decision processes in medication-free pediatric OCD patients.
AB  - BACKGROUND: Decision-making in Obsessive Compulsive Disorder has typically been
      investigated in the adult population. Computational approaches have recently
      started to get integrated into these studies. However, decision-making research
      in pediatric OCD populations is scarce. METHODS: We investigated latent decision
      processes in 21 medication-free pediatric OCD patients and 23 healthy control
      participants. We hypothesized that OCD patients would be more cautious and less
      efficient in evidence accumulation than controls in a two alternative forced
      choice (2AFC) task. RESULTS: Pediatric OCD patients were less efficient than
      controls in accumulating perceptual evidence and showed a tendency to be more
      cautious. In comparison to post-correct decisions, OCD patients increased
      decision thresholds after erroneous decisions, whereas healthy controls decreased
      decision thresholds. These changes were coupled with weaker evidence accumulation
      after errors in both groups. LIMITATIONS: The small sample size limited the power
      of the study. CONCLUSIONS: Our results demonstrate poorer decision-making
      performance in pediatric OCD patients at the level of latent processes,
      specifically in terms of evidence accumulation.

PMID- 27690352
TI  - Reconsidering the definition of Major Depression based on Collaborative
      Psychiatric Epidemiology Surveys.
AB  - BACKGROUND: Diagnostic definitions for depressive disorders remain a debated
      topic, despite their central role in clinical practice and research. We use both
      recent evidence and nationally representative data to derive an empirically-based
      modification of DSM-IV/-5 Major Depressive Disorder (MDD). METHOD: A modified MDD
      diagnosis was derived by analyzing data from Collaborative Psychiatric
      Epidemiology Surveys, a multistage probability sample of adults (n=20 013; age >=
      18 years) in coterminous USA, Alaska and Hawaii. The old and the newly suggested
      MDD definitions were compared for their associated disability (WHO Disability
      Assessment Schedule and number of disability days in past month), suicide
      attempt, and other covariates. RESULTS: Our data-driven definition for major
      depression was "lack of interest to all or most things" plus four other symptoms
      from the set {weight gain, weight loss, insomnia, psychomotor retardation,
      fatigue, feelings of worthlessness, diminished ability to think/concentrate,
      suicidal ideation/attempt}. The new definition captured all the disability
      implied by MDD and excluded cases that showed no greater disability than the
      general population nor increased risk of suicide attempts. The lifetime
      prevalence of the new diagnosis was 14.7% (95% CI=14-15.4%) of the population,
      slightly less than for the old definition (16.4%; CI=15.4-17.3%). LIMITATIONS:
      Only conservative modifications of MDD could be studied, because of restrictions
      in the symptom data. CONCLUSIONS: With only small adjusting, the new definition
      for major depression may be more clinically relevant than the old one, and could
      serve as a conservative replacement for the old definition.

PMID- 27690353
TI  - Fixed-dose versus separate drug combinations for antihypertensive treatment:
      literature review.
AB  - INTRODUCTION: Hypertension requires effective interventions to reduce
      cardiovascular morbidity and mortality. Drug therapies have achieved optimal
      blood pressure levels in affected patients. Recent clinical guidelines suggest
      drug combinations a fact that has led to the development of various fixed-dose
      combinations. OBJECTIVE: To find the best available evidence about the
      effectiveness of antihypertensive drugs in fixed-dose combinations compared with
      separate dose combinations for blood pressure control, treatment adherence and
      reducing cardiovascular morbidity and mortality. METHODS: Systematic literature
      search of the best evidence available in the following databases was performed:
      MEDLINE/PubMed, LILACS, Cochrane and institutional publications of WHO and PAHO.
      RESULTS: Two meta-analyses comparing the two combinations were found, in both
      studies medication compliance was evaluated, no control of blood pressure or
      effects on cardiovascular events was assessed. Both studies are of very low
      quality of evidence due to limitations in search methodology, suboptimal quality
      of the included studies and heterogeneity of the analyzed variables. WHO drug use
      policies for antihypertensive drugs do not suggest fixed-drug combinations. These
      combinations are not included in Chile's national drug formulary. CONCLUSION:
      Well-designed studies are required to demonstrate the effectiveness of
      antihypertensive drugs in fixed-dose combination compared with separate dose
      combinations for controlling blood pressure, treatment adherence and reducing
      cardiovascular morbidity and mortality.

PMID- 27690354
TI  - Correction: Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator
      Complex Causes Lethal Dilated Cardiomyopathy in Mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0160755.].

PMID- 27690355
TI  - Admixture in Latin America.
AB  - Latin Americans arguably represent the largest recently admixed populations in
      the world. This reflects a history of massive settlement by immigrants (mostly
      Europeans and Africans) and their variable admixture with Natives, starting in
      1492. This process resulted in the population of Latin America showing an
      extensive genetic and phenotypic diversity. Here we review how genetic analyses
      are being applied to examine the demographic history of this population,
      including patterns of mating, population structure and ancestry. The admixture
      history of Latin America, and the resulting extensive diversity of the region,
      represents a natural experiment offering an advantageous setting for genetic
      association studies. We review how recent analyses in Latin Americans are
      contributing to elucidating the genetic architecture of human complex traits.

PMID- 27690356
TI  - Impact of Malocclusion on the Quality of Life of Brazilian Adolescents: A
      Population-Based Study.
AB  - The objective of this study was to evaluate the impact of malocclusion on the
      quality of life (QOL) of adolescents in Brazil. We carried out a cross-sectional
      study in a sample population of 1015 schoolchildren aged 12 to 15 years from Sao
      Luis, Maranhao, Brazil. The explanatory variable was malocclusion, evaluated on
      the basis of the normative need or the adolescent's self-perceived need for
      dental treatment. Normative need for dental treatment was determined by
      professional diagnosis, made on the basis of Angle's classification, the Dental
      Aesthetic Index, and other morphological deviations (e.g., posterior crossbite,
      posterior open bite, and deep overbite). We analyzed the impact of malocclusion
      on the QOL using the Portuguese version of the Oral Health Impact Profile-14.
      Associations were estimated by using the prevalence ratio (PR) in Poisson
      regression analysis, with hierarchized modeling. An alpha of 5% was adopted as
      the criterion for statistical significance. The QOL of adolescents was impacted
      by malocclusion, classified by a normative need for treatment according to the
      Dental Aesthetic Index (PR = 1.27; 95% confidence interval [CI] = 1.03-1.56) or
      by the self-perceived need for treatment (PR = 2.54; 95% CI = 1.81-3.56). Certain
      sociodemographic variables, including the head of the family (PR = 1.52; 95% CI =
      1.02-2.23), greater educational level of the head of the family (PR = 0.32; 95%
      CI = 0.17-0.61), and female sex (PR = 1.40; 95% CI = 1.05-1.89), had negative
      associations with QOL. We conclude that malocclusion has a negative impact on the
      QOL of adolescents, associated with socioeconomic conditions and the cosmetic
      effects of malocclusion.

PMID- 27690357
TI  - Motility and microtubule depolymerization mechanisms of the Kinesin-8 motor,
      KIF19A.
AB  - The kinesin-8 motor, KIF19A, accumulates at cilia tips and controls cilium
      length. Defective KIF19A leads to hydrocephalus and female infertility because of
      abnormally elongated cilia. Uniquely among kinesins, KIF19A possesses the dual
      functions of motility along ciliary microtubules and depolymerization of
      microtubules. To elucidate the molecular mechanisms of these functions we solved
      the crystal structure of its motor domain and determined its cryo-electron
      microscopy structure complexed with a microtubule. The features of KIF19A that
      enable its dual function are clustered on its microtubule-binding side.
      Unexpectedly, a destabilized switch II coordinates with a destabilized L8 to
      enable KIF19A to adjust to both straight and curved microtubule protofilaments.
      The basic clusters of L2 and L12 tether the microtubule. The long L2 with a
      characteristic acidic-hydrophobic-basic sequence effectively stabilizes the
      curved conformation of microtubule ends. Hence, KIF19A utilizes multiple
      strategies to accomplish the dual functions of motility and microtubule
      depolymerization by ATP hydrolysis.

PMID- 27690358
TI  - Formulation and communication of evaluative forensic science expert opinion-A
      GHEP-ISFG contribution to the establishment of standards.
AB  - Communicating and interpreting genetic evidence in the administration of justice
      is currently a matter of great concern, due to the theoretical and technical
      complexity of the evaluative reporting and large difference in expertise between
      forensic experts and law professionals. A large number of initiatives have been
      taken trying to bridge this gap, contributing to the education of both parties.
      Results however have not been very encouraging, as most of these initiatives try
      to cope globally with the problem, addressing simultaneously theoretical and
      technical approaches which are in a quite heterogeneous state of development and
      validation. In consequence, the extension and complexity of the resulting
      documents disheartens their study by professionals (both jurists and geneticists)
      and makes a consensus very hard to reach even among the genetic experts'
      community. Here we propose a 'back-to-basics', example-driven approach, in which
      a model report for the two most common situations faced by forensic laboratories
      is presented. We do hope that this strategy will provide a solid basis for a
      stepwise generalisation.

PMID- 27690359
TI  - Safely Discharging Infants with Bronchiolitis from an Emergency Department: A
      Five Step Guide for Pediatricians.
AB  - Recent publications have established the pulse oxygen saturation (SpO2) threshold
      of 90% for the hospitalization and discharge of infant patients with
      bronchiolitis. However, there is no clear recommendation regarding the Emergency
      Department (ED) observation period necessary before allowing safe home discharge
      for patients with SpO2 above 90%-92%. Our primary aims were to evaluate the risk
      factors associated with delayed desaturation in infants with SpO2 >= 92% on
      arrival at the ED as well as the ED observation period necessary before allowing
      safe home discharge. A secondary aim was to identify the risk factors for ED
      readmission. Of 581 episodes of bronchiolitis in patients < 1 year old admitted
      to the ED, only 47 (8%) had SpO2 < 92% on arrival there, although 106 (18%)
      exhibited a delayed desaturation (to < 92%) during ED observation. Female sex,
      age < 3 months old, ED readmission, more severe initial clinical presentation,
      and higher pCO2 level (> 6KPa) were risk factors for delayed desaturation with OR
      varying from 1.7 to 7.5. In patients < 3 months old, mean desaturation occured
      later than in older patients [6.0 hours (IQR 3.0-14.0) vs. 3.0 hours (IQR 2.0
      6.0), P = 0.0018]. In 95% of patients with a delayed desaturation this decrease
      occurred within 25 hours for patients < 3 months old and within 11 hours for
      patients >= 3 months old. In patients < 3 months old with respiratory rates above
      the normal range for their age the desaturation occurred earlier than in patients
      < 3 months with normal respiratory rates [4.4 hours (IQR 3.0-11.7) vs. 14.6 hours
      (IQR 7.6-22.2), P = 0.037]. Based on the present study's results, we propose a
      five step guide for pediatricians on discharging children with bronchiolitis from
      the ED. By using the threshold of an 11 hour ED observation period for patients
      >= 3 months old and a 25 hour period for patients < 3 months old we are able to
      detect 95% of the patients with bronchiolitis who are at risk of delayed
      desaturation.

PMID- 27690360
TI  - Exposure to Corticosterone Affects Host Resistance, but Not Tolerance, to an
      Emerging Fungal Pathogen.
AB  - Host responses to pathogens include defenses that reduce infection burden (i.e.,
      resistance) and traits that reduce the fitness consequences of an infection
      (i.e., tolerance). Resistance and tolerance are affected by an organism's
      physiological status. Corticosterone ("CORT") is a hormone that is associated
      with the regulation of many physiological processes, including metabolism and
      reproduction. Because of its role in the stress response, CORT is also considered
      the primary vertebrate stress hormone. When secreted at high levels, CORT is
      generally thought to be immunosuppressive. Despite the known association between
      stress and disease resistance in domesticated organisms, it is unclear whether
      these associations are ecologically and evolutionary relevant in wildlife
      species. We conducted a 3x3 fully crossed experiment in which we exposed American
      toads (Anaxyrus [Bufo] americanus) to one of three levels of exogenous CORT (no
      CORT, low CORT, or high CORT) and then to either low or high doses of the
      pathogenic chytrid fungus Batrachochytrium dendrobatidis ("Bd") or a sham
      exposure treatment. We assessed Bd infection levels and tested how CORT and Bd
      affected toad resistance, tolerance, and mortality. Exposure to the high CORT
      treatment significantly elevated CORT release in toads; however, there was no
      difference between toads given no CORT or low CORT. Exposure to CORT and Bd each
      increased toad mortality, but they did not interact to affect mortality. Toads
      that were exposed to CORT had higher Bd resistance than toads exposed to ethanol
      controls/low CORT, a pattern opposite that of most studies on domesticated
      animals. Exposure to CORT did not affect toad tolerance to Bd. Collectively,
      these results show that physiological stressors can alter a host's response to a
      pathogen, but that the outcome might not be straightforward. Future studies that
      inhibit CORT secretion are needed to better our understanding of the relationship
      between stress physiology and disease resistance and tolerance in wild
      vertebrates.

PMID- 27690361
TI  - Anchoring of Heterochromatin to the Nuclear Lamina Reinforces Dosage Compensation
      Mediated Gene Repression.
AB  - Higher order chromosome structure and nuclear architecture can have profound
      effects on gene regulation. We analyzed how compartmentalizing the genome by
      tethering heterochromatic regions to the nuclear lamina affects dosage
      compensation in the nematode C. elegans. In this organism, the dosage
      compensation complex (DCC) binds both X chromosomes of hermaphrodites to repress
      transcription two-fold, thus balancing gene expression between XX hermaphrodites
      and XO males. X chromosome structure is disrupted by mutations in DCC subunits.
      Using X chromosome paint fluorescence microscopy, we found that X chromosome
      structure and subnuclear localization are also disrupted when the mechanisms that
      anchor heterochromatin to the nuclear lamina are defective. Strikingly, the
      heterochromatic left end of the X chromosome is less affected than the gene-rich
      middle region, which lacks heterochromatic anchors. These changes in X chromosome
      structure and subnuclear localization are accompanied by small, but significant
      levels of derepression of X-linked genes as measured by RNA-seq, without any
      observable defects in DCC localization and DCC-mediated changes in histone
      modifications. We propose a model in which heterochromatic tethers on the left
      arm of the X cooperate with the DCC to compact and peripherally relocate the X
      chromosomes, contributing to gene repression.

PMID- 27690362
TI  - Renal MR angiography and perfusion in the pig using hyperpolarized water.
AB  - PURPOSE: To study hyperpolarized water as an angiography and perfusion tracer in
      a large animal model. METHODS: Protons dissolved in deuterium oxide (D2 O) were
      hyperpolarized in a SPINlab dissolution dynamic nuclear polarization (dDNP)
      polarizer and subsequently investigated in vivo in a pig model at 3 Tesla (T).
      Approximately 15 mL of hyperpolarized water was injected in the renal artery by
      hand over 4-5 s. RESULTS: A liquid state polarization of 5.3 +/- 0.9% of 3.8 M
      protons in 15 mL of deuterium oxide was achieved with a T1 of 24 +/- 1 s. This
      allowed injection through an arterial catheter into the renal artery and
      subsequently high-contrast imaging of the entire kidney parenchyma over several
      seconds. The dynamic images allow quantification of tissue perfusion, with a mean
      cortical perfusion of 504 +/- 123 mL/100 mL/min. CONCLUSION: Hyperpolarized water
      MR imaging was successfully demonstrated as a renal angiography and perfusion
      method. Quantitative perfusion maps of the kidney were obtained in agreement with
      literature and control experiments with gadolinium contrast. Magn Reson Med
      78:1131-1135, 2017. (c) 2016 International Society for Magnetic Resonance in
      Medicine.

PMID- 27690363
TI  - Hydrogenation of Esters to Alcohols Catalyzed by Defined Manganese Pincer
      Complexes.
AB  - The first manganese-catalyzed hydrogenation of esters to alcohols has been
      developed. The combination of Mn(CO)5 Br with [HN(CH2 CH2 P(Et)2 )2 ] leads to a
      mixture of cationic and neutral Mn PNP pincer complexes, which enable the
      reduction of various ester substrates, including aromatic and aliphatic esters as
      well as diesters and lactones. Notably, related pincer complexes with isopropyl
      or cyclohexyl substituents showed very low activity.

PMID- 27690364
TI  - Maximum Bite Force of Edentulous Patients before and after Dental Implant
      Rehabilitation: Long-Term Follow-Up and Facial Type Influence.
AB  - PURPOSE: (1) To evaluate patients' long-term maximum bite force (MBF) after
      rehabilitation with mandibular implant-supported prosthesis, (2) to assess the
      influence of facial pattern in MBF, and (3) to evaluate the relation between the
      dominant chewing side and MBF. MATERIALS AND METHODS: Twenty-nine patients were
      selected. Pre- (T0) and immediate post-rehabilitation (T1) data of MBF were
      collected. In a follow-up visit 3 to 5 years after rehabilitation (T2), 24
      patients participated. The patients were asked about dominant chewing side, and
      facial pattern was obtained by the initial lateral radiographs. RESULTS: There
      was statistically significant increase in MBF in T1 - T0 = 5.4 +/- 4.3 kgf, T2 -
      T1 = 5.5 +/- 6.0 kgf. There was no statistically significant difference in MBF
      considering facial type, brachyfacial (T0 = 4.4, T1 = 10.7, T2 = 17.6 kgf),
      mesofacial (T0 = 4.1, T1 = 9.7, T2 = 16.5 kgf), and dolichofacial (T0 = 3.4, T1 =
      7.9, T2 = 12.6 kgf). CONCLUSIONS: There was no statistically significant relation
      between MBF and the dominant chewing side. It can be concluded that mandibular
      rehabilitation with dental implants improves MBF independent of the facial
      pattern and dominant chewing side.

PMID- 27690366
TI  - Rate of rise in diastolic blood pressure influences vascular sympathetic response
      to mental stress.
AB  - KEY POINTS: Research indicates that individuals may experience a rise (positive
      responders) or fall (negative responders) in muscle sympathetic nerve activity
      (MSNA) during mental stress. In this study, we examined the early blood pressure
      responses (including the peak, time of peak and rate of rise in blood pressure)
      to mental stress in positive and negative responders. Negative MSNA responders to
      mental stress exhibit a more rapid rise in diastolic pressure at the onset of the
      stressor, suggesting a baroreflex-mediated suppression of MSNA. In positive
      responders there is a more sluggish rise in blood pressure during mental stress,
      which appears to be MSNA-driven. This study suggests that whether MSNA has a role
      in the pressor response is dependent upon the reactivity of blood pressure early
      in the task. ABSTRACT: Research indicates that individuals may experience a rise
      (positive responders) or fall (negative responders) in muscle sympathetic nerve
      activity (MSNA) during mental stress. The aim was to examine the early blood
      pressure response to stress in positive and negative responders and thus its
      influence on the direction of change in MSNA. Blood pressure and MSNA were
      recorded continuously in 21 healthy young males during 2 min mental stressors
      (mental arithmetic, Stroop test) and physical stressors (cold pressor, handgrip
      exercise, post-exercise ischaemia). Participants were classified as negative or
      positive responders according to the direction of the mean change in MSNA during
      the stressor tasks. The peak changes, time of peak and rate of changes in blood
      pressure were compared between groups. During mental arithmetic negative
      responders experienced a significantly greater rate of rise in diastolic blood
      pressure in the first minute of the task (1.3 +/- 0.5 mmHg s-1 ) compared with
      positive responders (0.4 +/- 0.1 mmHg s-1 ; P = 0.03). Similar results were found
      for the Stroop test. Physical tasks elicited robust parallel increases in blood
      pressure and MSNA across participants. It is concluded that negative MSNA
      responders to mental stress exhibit a more rapid rise in diastolic pressure at
      the onset of the stressor, suggesting a baroreflex-mediated suppression of MSNA.
      In positive responders there is a more sluggish rise in blood pressure during
      mental stress, which appears to be MSNA-driven. This study suggests that whether
      MSNA has a role in the pressor response is dependent upon the reactivity of blood
      pressure early in the task.

PMID- 27690365
TI  - Mesoscale imaging with cryo-light and X-rays: Larger than molecular machines,
      smaller than a cell.
AB  - In the context of cell biology, the term mesoscale describes length scales
      ranging from that of an individual cell, down to the size of the molecular
      machines. In this spatial regime, small building blocks self-organise to form
      large, functional structures. A comprehensive set of rules governing mesoscale
      self-organisation has not been established, making the prediction of many cell
      behaviours difficult, if not impossible. Our knowledge of mesoscale biology comes
      from experimental data, in particular, imaging. Here, we explore the application
      of soft X-ray tomography (SXT) to imaging the mesoscale, and describe the
      structural insights this technology can generate. We also discuss how SXT imaging
      is complemented by the addition of correlative fluorescence data measured from
      the same cell. This combination of two discrete imaging modalities produces a 3D
      view of the cell that blends high-resolution structural information with precise
      molecular localisation data.

PMID- 27690368
TI  - Hereditary Dopamine Transporter Deficiency Syndrome: Challenges in Diagnosis and
      Treatment.
AB  - Hereditary dopamine transporter deficiency syndrome (DTDS) is a neurotransmitter
      disorder caused by a defect in the neuronal uptake of dopamine. To date, 20
      patients are reported in the literature, and we present 2 additional patients
      with DTDS harboring novel homozygous SLC6A3 gene mutations. Patient A is an 8
      month-old male with neonatal-onset hypotonia, who developed orolingual dyskinetic
      movements and oculogyric crises after 4 months of age, with evolution to status
      dystonicus episodes. Patient B is a 4-year-old male who also had hypotonia since
      birth, with additional severe limb contractions and oculogyric crises after the
      age of 3 months, with a misdiagnosis of epileptic encephalopathy. Both patients
      had consanguineous parents and similar cerebrospinal fluid (CSF) neurotransmitter
      profiles with elevated homovanillic acid and increased the ratio of homovanillic
      acid to 5-hydroxyindoleacetic acid. Diagnostic delay is 4 months, and 3 years 9
      months, respectively. Treatment response to levodopa is poor. Early infantile
      onset progressive dystonia with oculogyric crises, hypotonia, developmental
      delay, and CSF neurotransmitter profile led to a diagnosis of DTDS in these two
      patients. Management of hyperkinetic movement disorder, status dystonicus, and
      feeding difficulties are challenging. Detailed phenotyping of individual patients
      along with treatment response should provide insight into dopamine homeostasis.

PMID- 27690367
TI  - Decision Making Impairment: A Shared Vulnerability in Obesity, Gambling Disorder
      and Substance Use Disorders?
AB  - INTRODUCTION: Addictions are associated with decision making impairments. The
      present study explores decision making in Substance use disorder (SUD), Gambling
      disorder (GD) and Obesity (OB) when assessed by Iowa Gambling Task (IGT) and
      compares them with healthy controls (HC). METHODS: For the aims of this study,
      591 participants (194 HC, 178 GD, 113 OB, 106 SUD) were assessed according to DSM
      criteria, completed a sociodemographic interview and conducted the IGT. RESULTS:
      SUD, GD and OB present impaired decision making when compared to the HC in the
      overall task and task learning, however no differences are found for the overall
      performance in the IGT among the clinical groups. Results also reveal some
      specific learning across the task patterns within the clinical groups: OB
      maintains negative scores until the third set where learning starts but with a
      less extend to HC, SUD presents an early learning followed by a progressive
      although slow improvement and GD presents more random choices with no learning.
      CONCLUSIONS: Decision making impairments are present in the studied clinical
      samples and they display individual differences in the task learning. Results can
      help understanding the underlying mechanisms of OB and addiction behaviors as
      well as improve current clinical treatments.

PMID- 27690370
TI  - Magnetometry of Individual Polycrystalline Ferromagnetic Nanowires.
AB  - Ferromagnetic nanowires are finding use as untethered sensors and actuators for
      probing micro- and nanoscale biophysical phenomena, such as for localized sensing
      and application of forces and torques on biological samples, for tissue heating
      through magnetic hyperthermia, and for microrheology. Quantifying the magnetic
      properties of individual isolated nanowires is crucial for such applications.
      Dynamic cantilever magnetometry is used to measure the magnetic properties of
      individual sub-500 nm diameter polycrystalline nanowires of Ni and Ni80 Co20
      fabricated by template-assisted electrochemical deposition. The values are
      compared with bulk, ensemble measurements when the nanowires are still embedded
      within their growth matrix. It is found that single-particle and ensemble
      measurements of nanowires yield significantly different results that reflect
      inter-nanowire interactions and chemical modifications of the sample during the
      release process from the growth matrix. The results highlight the importance of
      performing single-particle characterization for objects that will be used as
      individual magnetic nanoactuators or nanosensors in biomedical applications.

PMID- 27690371
TI  - Economical, Plain, and Rapid Authentication of Actaea racemosa L. (syn.
      Cimicifuga racemosa, Black Cohosh) Herbal Raw Material by Resilient RP-PDA-HPLC
      and Chemometric Analysis.
AB  - INTRODUCTION: The medicinal plant Actaea racemosa L. (Ranunculaceae, aka black
      cohosh) is widely used to treat climacteric complaints as an alternative to
      hormone substitution. Recent trials prove efficacy and safety of the approved
      herbal medicinal products from extracts of pharmaceutical quality. This led to
      worldwide increasing sales. A higher demand for the plant material results in
      problems with economically motivated adulteration. Thus, reliable tools for
      herbal drug authentication are necessary. OBJECTIVE: To develop an economical,
      plain, and rapid method to distinguish between closely related American and Asian
      Actaea species, using securely established and resilient analytical methods
      coupled to a chemometric evaluation of the resulting data. METHODOLOGY: We
      developed and validated a RP-PDA-HPLC method including an extraction by ultra
      sonication to determine the genuine contents of partly hydrolysis-sensitive
      polyphenols in Actaea racemosa roots and rhizomes, and applied it to a large
      number of 203 Actaea samples consisting of seven species. RESULTS: We were able
      to generate reliable data with regards to the polyphenolic esters in the samples.
      The evaluation of this data by principle component analysis (PCA) made a
      discrimination between Asian Actaea species (sheng ma), one American Actaea
      species (Appalachian bugbane), and A. racemosa possible. CONCLUSION: The
      developed RP-PDA-HPLC method coupled to PCA is an excellent tool for
      authentication of the Actaea racemosa herbal drug, and can be a powerful addition
      to the TLC methods used in the dedicated pharmacopoeias, and is a promising
      alternative to expensive and lots of expertise requiring methods. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27690369
TI  - DNA methylation alterations in the pathogenesis of lupus.
AB  - Although lupus is, by definition, associated with genetic and immunological
      factors, its molecular mechanisms remain unclear. The up-to-date research
      findings point out that various genetic and epigenetic factors, especially gene
      specific and site-specific methylation, are believed to contribute to the
      initiation and development of systemic lupus erythematosus (SLE). This review
      presents and summarizes the association between abnormal DNA methylation of
      immune-related cells and lupus-like diseases, as well as the possible mechanisms
      of immune disorder caused by DNA methylation, aiming at a better understanding of
      the roles of aberrant DNA methylation in the initiation and development of
      certain forms of lupus and providing a new insight into promising therapeutic
      regimens in lupus-like diseases.

PMID- 27690372
TI  - Isotropic Conduction Network and Defect Chemistry in Mg3+delta Sb2 -Based Layered
      Zintl Compounds with High Thermoelectric Performance.
AB  - Thermoelectric performance in the layered Zintl phase n-type Mg3+delta (Sb,Bi)2
      is reported. Insertion of the excess Mg into the compounds is crucial for
      realizing n-type carrier transport with multivalley and isotropic character. An
      excellent ZT of 1.51 +/- 0.06 at 716 K is achieved in the sintered polycrystals
      at the composition of Mg3.2 Sb1.5 Bi0.49 Te0.01 .

PMID- 27690373
TI  - Investigating cellulose derived glycosaminoglycan mimetic scaffolds for cartilage
      tissue engineering applications.
AB  - Articular cartilage has a limited capacity to heal and, currently, no treatment
      exists that can restore normal hyaline cartilage. Creating tissue engineering
      scaffolds that more closely mimic the native extracellular matrix may be an
      attractive approach. Glycosaminoglycans, which are present in native cartilage
      tissue, provide signalling and structural cues to cells. This study evaluated the
      use of a glycosaminoglycan mimetic, derived from cellulose, as a potential
      scaffold for cartilage repair applications. Fully sulfated sodium cellulose
      sulfate (NaCS) was initially evaluated in soluble form as an additive to cell
      culture media. Human mesenchymal stem cell (MSC) chondrogenesis in pellet culture
      was enhanced with 0.01% NaCS added to induction media as demonstrated by
      significantly higher gene expression for type II collagen and aggrecan. NaCS was
      combined with gelatine to form fibrous scaffolds using the electrospinning
      technique. Scaffolds were characterized for fibre morphology, overall hydrolytic
      stability, protein/growth factor interaction and for supporting MSC
      chondrogenesis in vitro. Scaffolds immersed in phosphate buffered saline for up
      to 56 days had no changes in swelling and no dissolution of NaCS as compared to
      day 0. Increasing concentrations of the model protein lysozyme and transforming
      growth factor-beta3 were detected on scaffolds with increasing concentrations of
      NaCS (p < 0.05). MSC chondrogenesis was enhanced on the scaffold with the lowest
      NaCS concentration as seen with the highest collagen type II production, collagen
      type II immunostaining, and expression of cartilage-specific genes. These studies
      demonstrate the feasibility of cellulose sulfate as a scaffolding material for
      cartilage tissue engineering. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27690374
TI  - A Novel Approach to Developing Biomimetic ("Nacre-Like") Metal-Compliant-Phase
      (Nickel-Alumina) Ceramics through Coextrusion.
AB  - Bioinspired "brick-and-mortar" alumina ceramics containing a nickel compliant
      phase are synthesized by coextrusion of alumina and nickel oxide. Results show
      that these structures are coarser yet exhibit exceptional resistance-curve
      behavior with a fracture toughness three or more times higher than that of
      alumina, consistent with significant extrinsic toughening, from crack bridging
      and "brick" pull-out, in the image of natural nacre.

PMID- 27690375
TI  - A Novel Entry/Uncoating Assay Reveals the Presence of at Least Two Species of
      Viral Capsids During Synchronized HIV-1 Infection.
AB  - To better characterize the behavior of HIV-1 capsids we developed EURT, for
      Entry/Uncoating assay based on core-packaged RNA availability and Translation.
      EURT is an alternative to Blam-Vpr, but as reporter RNA translation relies on
      core opening, it can be used to study viral capsids behavior. Our study reveals
      the existence of two major capsid species, a dead end one in which the viral
      genome is readily exposed to the cytoplasm and a functional one in which such
      exposure requires artificial core destabilization. Although reverse transcription
      drives a faster loss of susceptibility of viral cores to high doses of PF74, it
      does not lead to higher exposure of the viral genome, implying that viral cores
      protect the genome irrespectively of reverse transcription. Lastly, IFNalpha
      drifts cores from functional to non-functional species, revealing a novel core
      destabilizing activity. This assay sheds new light on the behavior of viral cores
      inside target cells.

PMID- 27690376
TI  - Diversity and Variation of Bacterial Community Revealed by MiSeq Sequencing in
      Chinese Dark Teas.
AB  - Chinese dark teas (CDTs) are now among the popular tea beverages worldwide due to
      their unique health benefits. Because the production of CDTs involves
      fermentation that is characterized by the effect of microbes, microorganisms are
      believed to play critical roles in the determination of the chemical
      characteristics of CDTs. Some dominant fungi have been identified from CDTs. In
      contrast, little, if anything, is known about the composition of bacterial
      community in CDTs. This study was set to investigate the diversity and variation
      of bacterial community in four major types of CDTs from China. First, the
      composition of the bacterial community of CDTs was determined using MiSeq
      sequencing. From the four typical CDTs, a total of 238 genera that belong to 128
      families of bacteria were detected, including most of the families of beneficial
      bacteria known to be associated with fermented food. While different types of
      CDTs had generally distinct bacterial structures, the two types of brick teas
      produced from adjacent regions displayed strong similarity in bacterial
      composition, suggesting that the producing environment and processing condition
      perhaps together influence bacterial succession in CDTs. The global
      characterization of bacterial communities in CDTs is an essential first step for
      us to understand their function in fermentation and their potential impact on
      human health. Such knowledge will be important guidance for improving the
      production of CDTs with higher quality and elevated health benefits.

PMID- 27690377
TI  - Central Nervous System Injury - A Newly Observed Bystander Effect of Radiation.
AB  - The unintended side effects of cancer treatment are increasing recognized. Among
      these is a syndrome of long-term neurocognitive dysfunction called
      cancer/chemotherapy related cognitive impairment. To date, all studies examining
      the cognitive impact of cancer treatment have emphasized chemotherapy. Radiation
      induced bystander effects have been described in cell culture and, to a limited
      extent, in rodent model systems. The purpose of this study was to examine, for
      the first time, the impact of non-brain directed radiation therapy on the brain
      in order to elucidate its potential relationship with cancer/chemotherapy related
      cognitive impairment. To address this objective, female BALB/c mice received
      either a single 16 gray fraction of ionizing radiation to the right hind limb or
      three doses of methotrexate, once per week for three consecutive weeks. Mice were
      sacrificed either 3 or 30 days post-treatment and brain injury was determined via
      quantification of activated astrocytes and microglia. To characterize the effects
      of non-brain directed radiation on brain glucose metabolism, mice were evaluated
      by fluorodeoxygluocose positron emission tomography. A single fraction of 16 gray
      radiation resulted in global decreases in brain glucose metabolism, a significant
      increase in the number of activated astrocytes and microglia, and increased TNF
      alpha expression, all of which lasted up to 30 days post-treatment. This
      inflammatory response following radiation therapy was statistically
      indistinguishable from the neuroinflammation observed following methotrexate
      administration. In conclusion, non-brain directed radiation was sufficient to
      cause significant brain bystander injury as reflected by multifocal
      hypometabolism and persistent neuroinflammation. These findings suggest that
      radiation induces significant brain bystander effects distant from the irradiated
      cells and tissues. These effects may contribute to the development of cognitive
      dysfunction in treated human cancer patients and warrant further study.

PMID- 27690378
TI  - IL-33-Induced Cytokine Secretion and Survival of Mouse Eosinophils Is Promoted by
      Autocrine GM-CSF.
AB  - Eosinophils are major effector cells during allergic responses and helminth
      infections. Recent studies further highlight eosinophils as important players in
      many other biological processes. Therefore it is important to understand how
      these cells can be modulated in terms of survival and effector function. In the
      present study we investigated how eosinophils respond to the alarmin IL-33. We
      show that IL-33 promotes eosinophil survival in a ST2- and MyD88-dependent
      manner. IL-33-mediated protection from apoptosis was dependent on autocrine GM
      CSF release. In addition, GM-CSF increased the IL-33-induced secretion of IL-4
      and IL-13 from eosinophils. Unexpectedly, this effect was further enhanced by
      cross-linking of Siglec-F, a proposed inhibitory and apopotosis-inducing receptor
      on eosinophils. Co-culture experiments with eosinophils and macrophages revealed
      that the IL-33-induced release of IL-4 and IL-13 from eosinophils was required
      for differentiation of alternatively activated macrophages (AAMs). The
      differentiation of AAMs could be further increased in the presence of GM-CSF.
      These results indicate that cross-talk between Siglec-F and the receptors for IL
      33, LPS and GM-CSF plays an important role for efficient secretion of IL-4 and IL
      13. Deciphering the molecular details of this cross-talk could lead to the
      development of new therapeutic option to treat eosinophil-associated diseases.

PMID- 27690379
TI  - STN1 OB Fold Mutation Alters DNA Binding and Affects Selective Aspects of CST
      Function.
AB  - Mammalian CST (CTC1-STN1-TEN1) participates in multiple aspects of telomere
      replication and genome-wide recovery from replication stress. CST resembles
      Replication Protein A (RPA) in that it binds ssDNA and STN1 and TEN1 are
      structurally similar to RPA2 and RPA3. Conservation between CTC1 and RPA1 is less
      apparent. Currently the mechanism underlying CST action is largely unknown. Here
      we address CST mechanism by using a DNA-binding mutant, (STN1 OB-fold mutant,
      STN1-OBM) to examine the relationship between DNA binding and CST function. In
      vivo, STN1-OBM affects resolution of endogenous replication stress and telomere
      duplex replication but telomeric C-strand fill-in and new origin firing after
      exogenous replication stress are unaffected. These selective effects indicate
      mechanistic differences in CST action during resolution of different replication
      problems. In vitro binding studies show that STN1 directly engages both short and
      long ssDNA oligonucleotides, however STN1-OBM preferentially destabilizes binding
      to short substrates. The finding that STN1-OBM affects binding to only certain
      substrates starts to explain the in vivo separation of function observed in STN1
      OBM expressing cells. CST is expected to engage DNA substrates of varied length
      and structure as it acts to resolve different replication problems. Since STN1
      OBM will alter CST binding to only some of these substrates, the mutant should
      affect resolution of only a subset of replication problems, as was observed in
      the STN1-OBM cells. The in vitro studies also provide insight into CST binding
      mechanism. Like RPA, CST likely contacts DNA via multiple OB folds. However, the
      importance of STN1 for binding short substrates indicates differences in the
      architecture of CST and RPA DNA-protein complexes. Based on our results, we
      propose a dynamic DNA binding model that provides a general mechanism for CST
      action at diverse forms of replication stress.

PMID- 27690380
TI  - Flavonoids from Litsea japonica Inhibit AGEs Formation and Rat Lense Aldose
      Reductase In Vitro and Vessel Dilation in Zebrafish.
AB  - In our ongoing efforts to identify effective naturally sourced agents for the
      treating of diabetic complications, two new (1 and 2) and 11 known phenolic
      compounds (3-13) were isolated from an 80 % ethanol extract of Litsea japonica
      leaves. The structures of the new compounds were established by spectroscopic and
      chemical studies. These isolates (1-13) were subjected to an in vitro bioassay
      evaluating their inhibitory activity on advanced glycation end products formation
      and rat lens aldose reductase activity. Of the compounds evaluated, the
      flavonoids (3, 4, 6-8, 11, and 12) markedly inhibited advanced glycation end
      products formation, with IC50 values of 7.4-72.0 uM, compared with the positive
      control, aminoguanidine (IC50 = 975.9 uM). In the rat lens aldose reductase
      assay, consistent with the inhibition of advanced glycation end products
      formation, the flavonoids (3, 4, 6-8, 11, and 12) exhibited considerable
      inhibition of rat lens aldose reductase activity, with IC50 values of 1.1-12.5
      uM. In addition, the effects of kaempferol (4) and tiliroside (7) on the dilation
      of hyaloid-retinal vessels induced by high glucose in larval zebrafish were
      investigated. Only kaempferol significantly reduced the diameters of high glucose
      induced hyaloid-retinal vessels, by 52.2 % at 10 uM, compared with those in the
      high glucose-treated control group.

PMID- 27690381
TI  - Association of Apolipoprotein C3 Genetic Polymorphisms with the Risk of Ischemic
      Stroke in the Northern Chinese Han Population.
AB  - The apolipoprotein C3 (APOC3) gene, which is a member of the APOA1/C3/A4/A5 gene
      cluster, plays a crucial role in lipid metabolism. Dyslipidemia is an important
      risk factor for ischemic stroke. In the present study, we performed a hospital
      based case-control study of 895 ischemic stroke patients and 883 control subjects
      to examine the effects of four APOC3 single nucleotide polymorphisms (SNPs)
      (rs2854116, rs2854117, rs4520 and rs5128) on the risk of ischemic stroke in a
      northern Chinese Han population. The SNaPshot Multiplex sequencing assay was used
      for SNP genotyping, and the potential association of genotype distributions and
      allele frequencies with ischemic stroke was analyzed statistically. Compared with
      the GG genotype, the CC+GC genotype of rs5128 was significantly associated with
      an increased risk in females (adjusted OR = 3.38, 95% CI = 1.82-6.28, P <0.01)
      after all of the risk factors were adjusted for with logistic regression
      analyses. A similar relationship was found between the rs4520 polymorphism and
      ischemic stroke risk in Han Chinese women. Under a recessive genetic model, the
      TT+TC genotypes of this variant increased ischemic stroke risk (adjusted OR =
      2.05; 95% CI = 1.28-3.29; P <0.01). Haplotype analysis revealed that in males,
      the T-C-T-C haplotype of rs2854116-rs2854117-rs4520-rs5128 was significantly more
      frequent in the ischemic stroke group than in the control group (OR = 1.49, 95%
      CI = 1.18-1.87, P<0.01). The results of our study indicate that the APOC3
      polymorphisms contribute to ischemic stroke susceptibility in females in the
      northern Chinese Han population.

PMID- 27690382
TI  - Surface Functionalization of Metal Nanoparticles by Conjugated Metal-Ligand
      Interfacial Bonds: Impacts on Intraparticle Charge Transfer.
AB  - Noble metal nanoparticles represent a unique class of functional nanomaterials
      with physical and chemical properties that deviate markedly from those of their
      atomic and bulk forms. In order to stabilize the nanoparticles and further
      manipulate the materials properties, surface functionalization with organic
      molecules has been utilized as a powerful tool. Among those, mercapto derivatives
      have been used extensively as the ligands of choice for nanoparticle surface
      functionalization by taking advantage of the strong affinity of thiol moieties to
      transition metal surfaces forming (polar) metal-thiolate linkages. Yet, the
      nanoparticle material properties are generally discussed within the context of
      the two structural components, the metal cores and the organic capping layers,
      whereas the impacts of the metal-sulfur interfacial bonds are largely ignored
      because of the lack of interesting chemistry. In recent years, it has been found
      that metal nanoparticles may also be functionalized by stable metal-carbon (or
      even -nitrogen) covalent bonds. Because of the formation of dpi-ppi interactions
      between the transition-metal nanoparticles and terminal carbon moieties, the
      interfacial resistance at the metal-ligand interface is markedly reduced, leading
      to the emergence of unprecedented optical and electronic properties. In this
      Account, we summarize recent progress in the studies of metal nanoparticles
      functionalized by conjugated metal-ligand interfacial bonds that include metal
      carbene (M?C) and metal-acetylide (M-C=)/metal-vinylidene (M?C?C) bonds. Such
      interfacial bonds are readily formed by ligand self-assembly onto nanoparticle
      metal cores. The resulting nanoparticles exhibit apparent intraparticle charge
      delocalization between the particle-bound functional moieties, leading to the
      emergence of optical and electronic properties that are analogous to those of
      their dimeric counterparts, as manifested in spectroscopic and electrochemical
      measurements. This is first highlighted by ferrocene-functionalized nanoparticles
      that exhibit nanoparticle-mediated intervalence charge transfer (IVCT) among the
      particle-bound ferrocenyl moieties, as manifested in electrochemical and
      spectroscopic measurements. Such intraparticle charge delocalization has also
      been observed with other functional moieties such as pyrene and anthracene, where
      the photoluminescence emissions are consistent with those of their dimeric
      derivatives. Importantly, as such electronic communication occurs via a through
      bond pathway, it may be readily manipulated by the valence states of the
      nanoparticle cores as well as specific binding of selective molecules/ions to the
      organic capping shells. These fundamental insights may be exploited for diverse
      applications, ranging from chemical sensing to (nano)electronics and fuel cell
      electrochemistry. Several examples are included, such as sensitive detection of
      nitroaromatic derivatives, metal cations, and fluoride anions by fluorophore
      functionalized metal nanoparticles, fabrication of nanoparticle-bridged molecular
      dyads by, for instance, using nanoparticles cofunctionalized with 4-ethynyl-N,N
      diphenyl-aniline (electron donor) and 9-vinylanthracene (electron acceptor), and
      enhanced electrocatalytic activity of acetylene derivatives-functionalized
      metal/alloy nanoparticles for oxygen reduction reaction by manipulation of the
      metal core electron density and hence interactions with reaction intermediates.
      We conclude this Account with a perspective where inspiration from conventional
      organometallic chemistry may be exploited for more complicated nanoparticle
      surface functionalization through the formation of diverse metal-nonmetal bonds.
      This is a unique platform for ready manipulation of nanoparticle properties and
      applications.

PMID- 27690383
TI  - Discovery of N-Alkyl Catecholamides as Selective Phosphodiesterase-4 Inhibitors
      with Anti-neuroinflammation Potential Exhibiting Antidepressant-like Effects at
      Non-emetic Doses.
AB  - Depression involving neuroinflammation is one of the most common disabling and
      life-threatening psychiatric disorders. Phosphodiesterase 4 (PDE4) inhibitors
      produce potent antidepressant-like and cognition-enhancing effects. However,
      their clinical utility is limited by their major side effect of emesis. To obtain
      more selective PDE4 inhibitors with antidepressant and anti-neuroinflammation
      potential and less emesis, we designed and synthesized a series of N-alkyl
      catecholamides by modifying the 4-methoxybenzyl group of our hit compound,
      FCPE07, with an alkyl side chain. Among these compounds, 10 compounds displayed
      submicromolar IC50 values in the mid- to low-nanomolar range. Moreover, 4
      difluoromethoxybenzamides 10g and 10j, bearing isopropyl groups, exhibited the
      highest PDE4 inhibitory activities, with IC50 values in the low-nanomolar range
      and with higher selectivities for PDE4 (approximately 5000-fold and 2100-fold
      over other PDEs, respectively). Furthermore, compound 10j displayed anti
      neuroinflammation potential, promising antidepressant-like effects, and a zero
      incidence rate of emesis at 0.8 mg/kg within 180 min.

PMID- 27690384
TI  - Isotope Dilution UPLC-APCI-MS/MS Method for the Quantitative Measurement of
      Aromatic Diamines in Human Urine: Biomarkers of Diisocyanate Exposure.
AB  - Urinary diamines are biomarkers of diisocyanate exposure. Diisocyanates are
      considered as skin and respiratory sensitizers and are the most frequently
      reported cause of occupational asthma. Herein we report on the development and
      validation of an ultraperformance liquid chromatography-tandem mass spectrometry
      (UPLC-MS/MS) method for the measurement of five aromatic diamines, 4,4'
      methylenedianiline (MDA), 2,4-toluenediamine (4TDA), 2,6-toluenediamine (6TDA),
      1,5-naphthalenediamine (NDA), and p-phenylenediamine (PPDA) in human urine. The
      method incorporates sample preparation steps, which include a 4 h acid hydrolysis
      followed by high-throughput solid-phase extraction prior to chromatographic
      separation. Chromatographic separation was achieved using a C18 reversed phase
      column with gradient elution of basic mobile phases (pH 9.2). The duty cycle of
      the method was less than 5 min, including both the column equilibration and
      autosampler movement. Analytical detection was performed using positive ion
      atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) in
      scheduled multiple reaction monitoring (sMRM) mode. Excellent linearity was
      observed over standard calibration curve concentration ranges of 3 orders of
      magnitude with method detection limit ranging from 10 to 100 pg/mL. The interday
      and intraday reproducibility and accuracy were within +/-15%. This method is
      fast, accurate, and reproducible and is suitable for assessment of exposure to
      the most common aromatic diisocyanates within targeted groups as well as larger
      population studies such as the National Health and Nutrition Examination Survey
      (NHANES).

PMID- 27690385
TI  - Small-Molecule Probes Reveal Esterases with Persistent Activity in Dormant and
      Reactivating Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb) is the deadliest bacterial pathogen in the
      world. An estimated one-third of humans harbor Mtb in a dormant state. These
      asymptomatic, latent infections impede tuberculosis eradication due to the long
      term potential for reactivation. Dormant Mtb has reduced enzymatic activity, but
      hydrolases that remain active facilitate pathogen survival. We targeted Mtb
      esterases, a diverse set of enzymes in the serine hydrolase family, and studied
      their activities using both activity-based probes (ABPs) and fluorogenic esterase
      substrates. These small-molecule probes revealed functional esterases in active,
      dormant, and reactivating cultures. Using ABPs, we identified five esterases that
      remained active in dormant Mtb, including LipM (Rv2284), LipN (Rv2970c), CaeA
      (Rv2224c), Rv0183, and Rv1683. Three of these, CaeA, Rv0183, and Rv1683, were
      catalytically active in all three culture conditions. Fluorogenic probes
      additionally revealed LipH (Rv1399c), Culp1 (Rv1984c), and Rv3036c esterase
      activity in dormant and active cultures. Esterases with persistent activity are
      potential diagnostic biomarkers or therapeutic targets for Mtb-infected
      individuals with latent or active tuberculosis.

PMID- 27690386
TI  - Colloidal Spherical Quantum Wells with Near-Unity Photoluminescence Quantum Yield
      and Suppressed Blinking.
AB  - Thick inorganic shell endows colloidal nanocrystals (NCs) with enhanced
      photochemical stability and suppression of photoluminescence intermittency (also
      known as blinking). However, the progress of using thick-shell heterostructure
      NCs in applications has been limited, due to low photoluminescence quantum yield
      (PL QY ? 60%) at room temperature. Here, we demonstrate thick-shell NCs with
      CdS/CdSe/CdS seed/spherical quantum well/shell (SQW) geometry that exhibit near
      unity PL QY at room temperature and suppression of blinking. In SQW NCs, the
      lattice mismatch is diminished between the emissive CdSe layer and the
      surrounding CdS layers as a result of coherent strain, which suppresses the
      formation of misfit defects and consequently permits ~ 100% PL QY for SQW NCs
      with thick CdS shell (>= 5 nm). High PL QY of thick-shell SQW NCs are preserved
      even in concentrated dispersion and in film under thermal stress, which makes
      them promising candidates for applications in solid-state lightings and
      luminescent solar concentrators.

PMID- 27690387
TI  - Quantum Dots-Ligand Complex as Ratiometric Fluorescent Nanoprobe for Visual and
      Specific Detection of G-Quadruplex.
AB  - By complexing a nonionic G-quadruplex ligand with hybrid dual-emission quantum
      dots (QDs), a ratiometric fluorescent nanoprobe is developed for G-quadruplex
      detection in a sensitive and specific manner. The QDs nanohybrid comprised of a
      green-emission QD (gQD) and multiple red-emission QDs (rQDs) inside and outside
      of a silica shell, respectively, is utilized as the signal displaying unit. Only
      the presence of G-quadruplex can displace the ligand from QDs, breaking up the
      QDs-ligand complexation, and inducing the restoration of the rQDs fluorescence.
      Since the fluorescence of embedded gQD stays constant, variations of the dual
      emission intensity ratios display continuous color changes from green to bright
      orange, which can be clearly observed by the naked eye. Furthermore, by utilizing
      competitive binding of a cationic ligand versus the nonionic ligand toward G
      quadruplex, the nanoprobe is demonstrated to be applicable for assessing the
      affinity of a G-quadruplex-targeted anticancer drug candidate, exhibiting
      ratiometric fluorescence signals (reverse of that for G-quadruplex detection). By
      making use of the specificity of the ligand binding with G-quadruplex against a
      double helix, this nanoprobe is also demonstrated to be capable of sensitive
      detection of one-base mutation, exhibiting sequence-specific ratiometric
      fluorescence signals. By functionalizing with a nuclear localization peptide, the
      nanoprobe can be used for visualization of G-quadruplex in the nucleus of human
      cells.

PMID- 27690388
TI  - Bioluminescent Indicator for Highly Sensitive Analysis of Estrogenic Activity in
      a Cell-Based Format.
AB  - Estrogens regulate different physiological systems with wide ranges of
      concentrations. The rapid analysis of estrogens is crucially important for drug
      discovery and medical diagnosis, but quantitation of nanomolar estrogens in live
      cells persists as an important challenge. We herein describe a bioluminescent
      indicator used to detect low concentrations of estrogens quantitatively with a
      high signal-to-background ratio. The indicator comprises a ligand-binding domain
      of an estrogen receptor connected with its binding peptide, which is sandwiched
      between split fragments of a luciferase mutant. Results show that the indicator
      recovered its bioluminescence upon binding to 17beta-estradiol at concentrations
      higher than 1.0 * 10-10 M. The indicator was reactive to agonists but did not
      respond to antagonists. The indicator is expected to be applicable for rapid
      screening estrogenic compounds and inhibitors, facilitating the discovery of drug
      candidates in a high-throughput manner.

PMID- 27690389
TI  - Curcumin-Based "Enhanced SNAr" Promoted Ultrafast Fluorescent Probe for
      Thiophenols Detection in Aqueous Solution and in Living Cells.
AB  - We report herein a highly selective and sensitive turn-on fluorescent probe
      (compound 1) with a fast response time (less than 2 min) for thiophenol detection
      based on an "enhanced SNAr" reaction between thiophenols and a sulfonyl-ester
      moiety covalently attach to curcumin. Reaction of 1 in Hepes-MeOH (1:1, v/v, pH
      7.4) in the presence of 4-methylthiophenol (MTP) resulted in a remarkable
      enhancement of the fluorescence. A linear response in the presence of MTP of the
      relative fluorescent intensity (F - F0) of 1 at 536 nm in the 0-40 MUM MTP
      concentration range was found. A limit of detection (LOD) for the detection of
      MTP of 26 nM, based on the definition by IUPAC (CDL = 3 Sb/m), was calculated.
      Probe 1 was applied to monitor and imaging exogenous MTP in live cells and to the
      detection of MTP in real water samples.

PMID- 27690390
TI  - Resource Sharing Controls Gene Expression Bursting.
AB  - Episodic gene expression, with periods of high expression separated by periods of
      no expression, is a pervasive biological phenomenon. This bursty pattern of
      expression draws from a finite reservoir of expression machinery in a highly time
      variant way, i.e., requiring no resources most of the time but drawing heavily on
      them during short intense bursts, that intimately links expression bursting and
      resource sharing. Yet, most recent investigations have focused on specific
      molecular mechanisms intrinsic to the bursty behavior of individual genes, while
      little is known about the interplay between resource sharing and global
      expression bursting behavior. Here, we confine Escherichia coli cell extract in
      both cell-sized microfluidic chambers and lipid-based vesicles to explore how
      resource sharing influences expression bursting. Interestingly, expression burst
      size, but not burst frequency, is highly sensitive to the size of the shared
      transcription and translation resource pools. The intriguing implication of these
      results is that expression bursts are more readily amplified than initiated,
      suggesting that burst formation occurs through positive feedback or
      cooperativity. When extrapolated to prokaryotic cells, these results suggest that
      large translational bursts may be correlated with large transcriptional bursts.
      This correlation is supported by recently reported transcription and translation
      bursting studies in E. coli. The results reported here demonstrate a strong
      intimate link between global expression burst patterns and resource sharing, and
      they suggest that bursting plays an important role in optimizing the use of
      limited, shared expression resources.

PMID- 27690391
TI  - Concurrent Glycogen and Lactate Imaging with FTIR Spectroscopy To Spatially
      Localize Metabolic Parameters of the Glial Response Following Brain Ischemia.
AB  - Imaging energy metabolites as markers of the energy shuttle between glia and
      neurons following ischemia is an ongoing challenge. Traditional microscopies in
      combination with histochemistry reveal glycogen accumulation within glia
      following ischemia, indicating an altered metabolic profile. Although
      semiquantitative histochemical glycogen analysis is possible, the method suffers
      from typical confounding factors common to histochemistry, such as variation in
      reagent penetration and binding. In addition, histochemical detection of glycogen
      does not reveal information on the metabolic fate of glycogen (i.e., lactate
      production). Therefore, validation of a direct semiquantitative method to
      simultaneously image both brain glycogen and lactate in the same tissue section
      would benefit this research field. In this study, we demonstrate the first
      application of Fourier transform infrared (FTIR) spectroscopy for simultaneous
      direct spectroscopic imaging of brain glycogen and lactate, in situ within ex
      vivo tissue sections. Serial tissue sections were analyzed with anti-glial
      fibrillary acidic protein (GFAP) immunohistochemistry to provide a comparison
      between the glycogen and lactate distribution revealed by FTIR and the glial
      distribution revealed by GFAP immunohistochemistry. The distribution of glycogen
      revealed by FTIR spectroscopic imaging has been further compared with
      histochemical detection of glycogen on the adjacent tissue sections. This
      approach was then applied to study spatiotemporal disturbances in metabolism,
      relative to glia and neuronal populations, following cerebral ischemia in a
      murine model of stroke.

PMID- 27690392
TI  - Chemical Isotope Labeling LC-MS for High Coverage and Quantitative Profiling of
      the Hydroxyl Submetabolome in Metabolomics.
AB  - A key step in metabolomics is to perform accurate relative quantification of the
      metabolomes in comparative samples with high coverage. Hydroxyl-containing
      metabolites are an important class of the metabolome with diverse structures and
      physical/chemical properties; however, many of them are difficult to detect with
      high sensitivity. We present a high-performance chemical isotope labeling liquid
      chromatography mass spectrometry (LC-MS) technique for in-depth profiling of the
      hydroxyl submetabolome, which involves the use of acidic liquid-liquid extraction
      to enrich hydroxyl metabolites into ethyl acetate from an aqueous sample. After
      drying and then redissolving in acetonitrile, the metabolite extract is labeled
      using a base-activated 12C- or 13C-dansylation reaction. A fast step-gradient LC
      UV method is used to determine the total concentration of labeled metabolites. On
      the basis of the concentration information, a 12C-labeled individual sample is
      mixed with an equal mole amount of a 13C-labeled pool or control for relative
      metabolite quantification. The 12C-/13C-labeled mixtures are individually
      analyzed by LC-MS, and the resultant peak pairs of labeled metabolites in MS are
      measured for relative quantification and metabolite identification. A standard
      library of 85 hydroxyl compounds containing MS, retention time, and MS/MS
      information was constructed for positive metabolite identification based on
      matches of two or all three of these parameters with those of an unknown. Using
      human urine as an example, we analyzed samples of 1:1 12C-/13C-labeled urine in
      triplicate with triplicate runs per sample and detected an average of 3759 +/- 45
      peak pairs or metabolites per run and 3538 +/- 71 pairs per sample with 3093
      pairs in common (n = 9). Out of the 3093 peak pairs, 2304 pairs (75%) could be
      positively or putatively identified based on metabolome database searches,
      including 20 pairs positively identified using the dansylated hydroxyl standards
      library. The majority of detected metabolites were those containing hydroxyl
      groups. This technique opens a new avenue for the detailed characterization of
      the hydroxyl submetabolome in metabolomics research.

PMID- 27690393
TI  - Efficient Synthetic Approach to Linear Dasatinib-DNA Conjugates by Click
      Chemistry.
AB  - Two synthetic approaches to linear dasatinib-DNA conjugates via click chemistry
      are described. One approach involves the reaction of excess azido dasatinib
      derivative with 5'-(5-hexynyl) tagged DNAs and the other involves the reaction of
      excess alkynyl linked dasatinib with 5'-azido tagged DNA. The second approach
      using alkynyl derived dasatinib and 5'-azido tagged DNA yielded the corresponding
      dasatinib-DNA conjugates in higher yield (47% versus 10-33% for the first
      approach). Studies have shown these linear dasatinib-DNA conjugates derived gold
      nanoparticles exhibit efficacy against leukemia cancer cells with reduced
      toxicity toward normal cells compared to free dasatinib.

PMID- 27690394
TI  - Limits of Detection and Quantification of Electrochemical Quartz-Crystal
      Nanobalance in Platinum Electrochemistry and Electrocatalysis Research.
AB  - The electrochemical quartz-crystal nanobalance has been used in electrochemistry
      research for over three decades. It provides an atomic/molecular level insight
      into the nature of interfacial electrochemical phenomena by measuring in situ
      mass changes on the nanogram scale. The sensitivity of this technique remains
      unknown because there have been no attempts to determine its limits of detection
      (LOD) or quantification (LOQ). We propose an experimental approach for
      determining the values of LOD and LOQ for Pt electrodes in aqueous H2SO4
      solutions that employs cyclic voltammetry and frequency variation measurements.
      However, this methodology is also appropriate to other electrode materials and
      electrolytes. The LOD and LOQ values depend on the electrolyte concentration and
      decrease (i.e., the sensitivity increases) as the concentration decreases.
      Knowledge of the LOD and LOQ values determines the applicability of this
      technique in research on the oxidation and degradation of Pt catalysts employed
      in fuel cells.

PMID- 27690395
TI  - Catalytic Hydrogenation of Carbon Dioxide with Ammonia-Borane by Pincer-type
      Phosphorus Compound: A Theoretical Prediction.
AB  - Theoretically designed pincer-type phosphorus compound is found to be active for
      the hydrogenation of carbon dioxide (CO2) with ammonia-borane. DFT,
      ONIOM(CCSD(T):MP2), and CCSD(T) computational results demonstrated that the
      reaction occurs through the phosphorus-ligand cooperative catalysis function,
      which provides an unprecedented protocol for metal-free CO2 conversion. The
      phosphorus compounds with the NNN ligand are more active than those with the ONO
      ligand. The conjugate and planar ligand considerably improves the efficiency of
      the catalyst.

PMID- 27690396
TI  - Formation, Characterization, and Reactivity of a Nonheme Oxoiron(IV) Complex
      Derived from the Chiral Pentadentate Ligand asN4Py.
AB  - The chiral pentadentate low-spin (S = 1) oxoiron(IV) complex [FeIV(O)(asN4Py)]2+
      (2) was synthesized and spectroscopically characterized. Its formation kinetics,
      reactivity, and (enantio)selectivity in an oxygen-atom-transfer reaction was
      investigated in detail and compared to a similar pentadentate ligand-containing
      system.

PMID- 27690397
TI  - CoII4, CoII7, and a Series of CoII2LnIII (LnIII = NdIII, SmIII, GdIII, TbIII,
      DyIII) Coordination Clusters: Search for Single Molecule Magnets.
AB  - We report herein the syntheses and investigation of the magnetic properties of a
      CoII4 compound, a series of trinuclear CoII2LnIII (LnIII = NdIII, SmIII, GdIII,
      TbIII, DyIII) complexes, and a CoII7 complex. The homometallic CoII4 core was
      obtained from the reaction of Ln(NO3)3.xH2O/Co(NO3)2.6H2O/H2vab/Et3N in a
      0.5:0.5:1:2 ratio in methanol. Variation in synthetic conditions was necessary to
      get the desired CoII-LnIII complexes. The CoII-LnIII assembly was synthesized
      from Ln(NO3)3.xH2O/Co(OAc)2.4H2O/H2vab/NaOMe in a 0.4:0.5:1:1 ratio in methanol.
      The isostructural CoII2LnIII complexes have a core structure with the general
      formula [Co2Ln(Hvab)4(NO3)](NO3)2.MeOH.H2O, (where H2vab = 2-[(2-hydroxymethyl
      phenylimino)-methyl]-6-methoxy-phenol) with simultaneous crystallization of CoII7
      complex in each reaction. The magnetic investigation of these complexes reveals
      that both homometallic complexes and four CoII-LnIII complexes (except CoII
      NdIII) display behavior characteristic of single molecule magnets.

PMID- 27690398
TI  - Manifestation of Anomalous Weak Space-Charge-Density Acentricity for a Tl4HgBr6
      Single Crystal.
AB  - Density functional theory (DFT) calculations within the concept of the MBJ+U+SO
      (modified Becke-Johnson potential + U + spin orbit) approach were performed for a
      Tl4HgBr6 single crystal for the first time assuming weak noncentrosymmetry (space
      group P4nc). Excellent agreement was achieved between the calculated and
      experimental band-gap-energy magnitudes as well as the density of electronic
      states measured by the X-ray photoelectron spectroscopy method. It is a very
      principal result because usually the DFT calculations underestimate the energy
      gap values. In the present study, we carry out calculations of the optical
      properties (absorption coefficient, real and imaginary parts of the dielectric
      function, electron energy-loss spectrum, refractive index, extinction
      coefficient, and optical reflectivity dispersions). It has been established that
      the principal origin of the observed weak acentricity is determined by
      delocalized band states at the top of the valence band originating from the p
      states of the Br atoms.

PMID- 27690399
TI  - Controls on Nitrous Oxide Emissions from the Hyporheic Zones of Streams.
AB  - The magnitude and mechanisms of nitrous oxide (N2O) release from rivers and
      streams are actively debated. The complex interactions of hydrodynamic and
      biogeochemical controls on emissions of this important greenhouse gas preclude
      prediction of when and where N2O emissions will be significant. We present
      observations from column and large-scale flume experiments supporting an
      integrative model of N2O emissions from stream sediments. Our results show a
      distinct, replicable, pattern of nitrous oxide generation and consumption
      dictated by subsurface (hyporheic) residence times and biological nitrogen
      reduction rates. Within this model, N2O emission from stream sediments requires
      subsurface residence times (and microbially mediated reduction rates) be
      sufficiently long (and fast reacting) to produce N2O by nitrate reduction but
      also sufficiently short (or slow reacting) to limit N2O conversion to dinitrogen
      gas. Most subsurface exchange will not result in N2O emissions; only specific,
      intermediate, residence times (reaction rates) will both produce and release N2O
      to the stream. We also confirm previous observations that elevated nitrate and
      declining organic carbon reactivity increase N2O production, highlighting the
      importance of associated reaction rates in controlling N2O accumulation.
      Combined, these observations help constrain when N2O release will occur,
      providing a predictive link between stream geomorphology, hydrodynamics, and N2O
      emissions.

PMID- 27690400
TI  - Environmental Origins of Methylmercury Accumulated in Subarctic Estuarine Fish
      Indicated by Mercury Stable Isotopes.
AB  - Methylmercury (MeHg) exposure can cause adverse reproductive and
      neurodevelopmental health effects. Estuarine fish may be exposed to MeHg produced
      in rivers and their watersheds, benthic sediment, and the marine water column,
      but the relative importance of each source is poorly understood. We measured
      stable isotopes of mercury (delta202Hg, Delta199Hg, and Delta201Hg), carbon
      (delta13C), and nitrogen (delta15N) in fish with contrasting habitats from a
      large subarctic coastal ecosystem to better understand MeHg exposure sources. We
      identify two distinct food chains exposed to predominantly freshwater and marine
      MeHg sources but do not find evidence for a benthic marine MeHg signature. This
      is consistent with our previous research showing benthic sediment is a net sink
      for MeHg in the estuary. Marine fish display lower and less variable Delta199Hg
      values (0.780/00 to 1.770/00) than freshwater fish (0.720/00 to 3.140/00) and
      higher delta202Hg values (marine: 0.10/00 to 0.570/00; freshwater: -0.760/00 to
      0.150/00). We observe a shift in the Hg isotopic composition of juvenile and
      adult rainbow smelt (Osmerus mordax) when they transition between the freshwater
      and marine environment as their dominant foraging territory. The Hg isotopic
      composition of Atlantic salmon (Salmo salar) indicates they receive most of their
      MeHg from the marine environment despite a similar or longer duration spent in
      freshwater regions. We conclude that stable Hg isotopes effectively track fish
      MeHg exposure sources across different ontogenic stages.

PMID- 27690401
TI  - Light-Induced Activation of a Molybdenum Oxotransferase Model within a Ru(II)
      Mo(VI) Dyad.
AB  - Nature uses molybdenum-containing enzymes to catalyze oxygen atom transfer (OAT)
      from water to organic substrates. In these enzymes, the two electrons that are
      released during the reaction are rapidly removed, one at a time, by spatially
      separated electron transfer units. Inspired by this design, a Ru(II)-Mo(VI) dyad
      was synthesized and characterized, with the aim of accelerating the rate
      determining step in the cis-dioxo molybdenum-catalyzed OAT cycle, the transfer of
      an oxo ligand to triphenyl phosphine, via a photo-oxidation process. The dyad
      consists of a photoactive bis(bipyridyl)-phenanthroline ruthenium moiety that is
      covalently linked to a bioinspired cis-dioxo molybdenum thiosemicarbazone
      complex. The quantum yield and luminescence lifetimes of the dyad
      [Ru(bpy)2(L2)MoO2(solv)]2+ were determined. The major component of the
      luminescence decay in MeCN solution (tau = 1149 +/- 2 ns, 67%) corresponds
      closely to the lifetime of excited [Ru(bpy)2(phen-NH2)]2+, while the minor
      component (tau = 320 +/- 1 ns, 31%) matches that of [Ru(bpy)2(H2-L2)]2+. In
      addition, the (spectro)electrochemical properties of the system were
      investigated. Catalytic tests showed that the dyad-catalyzed OAT from dimethyl
      sulfoxide to triphenyl phosphine proceeds significantly faster upon irradiation
      with visible light than in the dark. Methylviologen acts as a mediator in the
      photoredox cycle, but it is regenerated and hence only required in stoichiometric
      amounts with respect to the catalyst rather than sacrificial amounts. It is
      proposed that oxidative quenching of the photoexcited Ru unit, followed by
      intramolecular electron transfer, leads to the production of a reactive one
      electron oxidized catalyst, which is not accessible by electrochemical methods. A
      significant, but less pronounced, rate enhancement was observed when an analogous
      bimolecular system was tested, indicating that intramolecular electron transfer
      between the photosensitizer and the catalytic center is more efficient than
      intermolecular electron transfer between the separate components.

PMID- 27690402
TI  - Polymorphism in Strontium Tungstate SrWO4 under Quasi-Hydrostatic Compression.
AB  - The structural and vibrational properties of SrWO4 have been studied
      experimentally up to 27 and 46 GPa, respectively, by angle-dispersive synchrotron
      X-ray diffraction and Raman spectroscopy measurements as well as using ab initio
      calculations. The existence of four polymorphs upon quasi-hydrostatic compression
      is reported. The three phase transitions were found at 11.5, 19.0, and 39.5 GPa.
      The ambient-pressure SrWO4 tetragonal scheelite-type structure (S.G. I41/a)
      undergoes a transition to a monoclinic fergusonite-type structure (S.G. I2/a) at
      11.5 GPa with a 1.5% volume decrease. Subsequently, at 19.0 GPa, another
      structural transformation takes place. Our calculations indicate two possible
      post-fergusonite phases, one monoclinic and the other orthorhombic. In the
      diffraction experiments, we observed the theoretically predicted monoclinic
      LaTaO4-type phase coexisting with the fergusonite-type phase up to 27 GPa. The
      coexistence of the two phases and the large volume collapse at the transition
      confirm a kinetic hindrance typical of first-order phase transitions. Significant
      changes in Raman spectra suggest a third pressure-induced transition at 39.5 GPa.
      The conclusions extracted from the experiments are complemented and supported by
      ab initio calculations. Our data provides insight into the structural mechanism
      of the first transition, with the formation of two additional W-O contacts. The
      fergusonite-type phase can be therefore considered as a structural bridge between
      the scheelite structure, composed of [WO4] tetrahedra, and the new higher
      pressure phases, which contain [WO6] octahedra. All the observed phases are
      compatible with the high-pressure structural systematics predicted for ABO4
      compounds using crystal-chemistry arguments such as the diagram proposed by
      Bastide.

PMID- 27690403
TI  - First Measurements of the Nitrogen Isotopic Composition of NOx from Biomass
      Burning.
AB  - The nitrogen isotopic composition (delta15N) of NOx (NO + NO2) was measured
      during the fourth Fire Lab at Missoula Experiment (FLAME-4). The delta15N-NOx
      produced by burning a variety of biomass types ranged from -7 to +120/00 (vs air
      N2). In the laboratory experiments, two types of emissions were sampled: "stack"
      fires where the emissions were measured within a few seconds of production from
      the fire and "chamber" fires where the emissions were held in a room for 1-2 h
      and sampled continuously. For both types of emissions sampled, the primary
      control on delta15N-NOx is the delta15N of the biomass burned (delta15N-biomass),
      although differences were found for delta15N-NOx between the two types of fires.
      For the stack emissions, delta15N-NOx = 0.41 * delta15N-biomass +1.0 (R2 = 0.83,
      p-value <0.001) and for the chamber fires, delta15N-NOx = 0.98 * delta15N-biomass
      +1.7 (R2 = 0.94, p-value <0.001). While a large range of delta15N-NOx values were
      observed, the strong relationship between delta15N-NOx and delta15N-biomass
      suggests that in any given environment, the delta15N-NOx can be predicted.

PMID- 27690404
TI  - Gas-Phase Mechanisms of the Reactions of Reduced Organic Nitrogen Compounds with
      OH Radicals.
AB  - Research on the fate of reduced organic nitrogen compounds in the atmosphere has
      gained momentum since the identification of their crucial role in particle
      nucleation and the scale up of carbon capture and storage technology which
      employs amine-based solvents. Reduced organic nitrogen compounds have strikingly
      different lifetimes against OH radicals, from hours for amines to days for amides
      to years for isocyanates, highlighting unique functional group reactivity. In
      this work, we use ab initio methods to investigate the gas-phase mechanisms
      governing the reactions of amines, amides, isocyanates and carbamates with OH
      radicals. We determine that N-H abstraction is only a viable mechanistic pathway
      for amines and we identify a reactive pathway in amides, the formyl C-H
      abstraction, not currently considered in structure-activity relationship (SAR)
      models. We then use our acquired mechanistic knowledge and tabulated literature
      experimental rate coefficients to calculate SAR factors for reduced organic
      nitrogen compounds. These proposed SAR factors are an improvement over existing
      SAR models because they predict the experimental rate coefficients of amines,
      amides, isocyanates, isothiocyanates, carbamates and thiocarbamates with OH
      radicals within a factor of 2, but more importantly because they are based on a
      sound fundamental mechanistic understanding of their reactivity.

PMID- 27690405
TI  - Defining a physical basis for diversity in protein self-assemblies using a
      minimal model.
AB  - Self-assembly of proteins into ordered, fibrillar structures is a commonly
      observed theme in biology. It has been observed that diverse set of proteins (e.g
      alpha-synuclein, insulin, TATA-box binding protein, Sup35, p53), independent of
      their sequence, native structure, or function could self-assemble into highly
      ordered structures known as amyloids. What are the crucial features underlying
      amyloidogenesis that make it so generic? Using coarse-grained simulations of
      peptide self-assembly, we argue that variation in two physical parameters-
      bending-stiffness of the polypeptide and strength of inter-molecular interactions
      can give rise to many of the structural features typically associated with
      amyloid self-assembly. We show that the interplay between these two factors gives
      rise to a rich phase diagram displaying high diversity in aggregated states. For
      certain parameters, we find a bimodal distribution for the order parameter
      implying the co-existence of ordered and disordered aggregates. Our findings may
      explain the experimentally observed variability including the 'off-pathway'
      aggregated structures. Further, we demonstrate that sequence-dependence and
      protein-specific signatures could be mapped to our coarse-grained framework to
      study self-assembly behavior of realistic systems such as the STVIIE peptide and
      Abeta42. The work also provides certain guiding principles which could be used to
      design novel peptides with desired self-assembly properties, by tuning a few
      physical parameters.

PMID- 27690406
TI  - Why is the Ir(III)-Mediated Amido Transfer Much Faster Than the Rh(III)-Mediated
      Reaction? - A Combined Experimental and Computational Study.
AB  - The mechanism of the Ir(III) and Rh(III)-mediated C-N coupling reaction, which is
      the key step of catalytic C-H amidation, was investigated in an integrated
      experimental and computational study. Novel amidating agents containing a 1,4,2
      dioxazole moiety allowed for designing a stoichiometric version of the catalytic
      C-N coupling reaction and giving access to reaction intermediates that reveal
      details about each step of the reaction. Both DFT and kinetic studies strongly
      point to a mechanism where the M(III) complex engages the amidating agent via
      oxidative coupling to form a M(V)-imido intermediate, which then undergoes
      migratory insertion to afford the final C-N coupled product. For the first time,
      the stoichiometric versions of the Ir and Rh-mediated amidation reaction were
      compared systematically to each other. Iridium reacts much faster than rhodium (~
      1100 times at 6.7  degrees C) with the oxidative coupling being so fast that the
      activation of the initial Ir(III)-complex becomes rate-limiting. In the case of
      Rh, the Rh-imido formation step is rate-limiting. These qualitative difference
      stems from a unique bonding feature of the dioxazole moiety and the relativistic
      contraction of the Ir(V), which affords much more favorable energetics for the
      reaction. For the first time, a full molecular orbital analysis is presented to
      rationalize and explain the electronic features that govern this behavior.

PMID- 27690407
TI  - Colloidal Single-Layer Quantum Dots with Lateral Confinement Effects on 2D
      Exciton.
AB  - Controlled lateral quantum confinement in single-layer transition-metal
      chalcogenides (TMCs) can potentially combine the unique properties of two
      dimensional (2D) exciton with the size-tunability of exciton energy, creating the
      single-layer quantum dots (SQDs) of 2D TMC materials. However, exploring such
      opportunities has been challenging due to the limited ability to produce well
      defined SQDs with sufficiently high quality and size control, in conjunction with
      the commonly observed inconsistency in the optical properties. Here, we report an
      effective method to synthesize high-quality and size-controlled SQDs of WSe2 via
      multilayer quantum dots (MQDs) precursors, which enables grasping a clear picture
      of the role of lateral confinement on the optical properties of the 2D exciton.
      From the single-particle optical spectra and polarization anisotropy of WSe2 SQDs
      of varying sizes in addition to their ensemble data, we reveal how the properties
      of 2D exciton in single-layer TMCs evolve with increasing lateral quantum
      confinement.

PMID- 27690408
TI  - Stimulation and Inhibition of Anaerobic Digestion by Nickel and Cobalt: A Rapid
      Assessment Using the Resazurin Reduction Assay.
AB  - Stimulation of anaerobic digestion by essential trace metals is beneficial from a
      practical point of view to enhance the biodegradability and degradation rate of
      wastes. Hence, a quick method to determine which metal species, and at what
      concentration, can optimize anaerobic digestion is of great interest to both
      researchers and operators. In this present study, we investigated the effect of
      nickel(II), cobalt(II), and their mixture, on the anaerobic digestion of
      synthetic municipal wastewater. Using a volumetric method, that is, measuring
      methane production over time, revealed that anaerobic digestion was stimulated by
      the addition of 5 mg L-1 nickel(II), and cobalt(II), and their mixture in day(s).
      However, using a novel resazurin reduction assay, and based on its change in rate
      over time, we evaluated both inhibition at 250 mg L-1 nickel(II) and cobalt(II),
      and also the stimulatory effect of 5 mg L-1 nickel(II), and cobalt(II), and their
      mixture, in just 6 h. By investigating the dynamic distribution of these metals
      in the liquid phase of the anaerobic system and kinetics of resazurin reduction
      by nickel spiked anaerobic sludge, the concentration of nickel(II) on anaerobic
      digestion performance was profiled. Three critical concentrations were
      determined; stimulation starting (around 1 mg L-1), stimulation ending (around
      100 mg L-1) and stimulation maximizing (around 10 mg L-1). Hence, we propose that
      the resazurin reduction assay is a novel and quick protocol for studying the
      stimulation of anaerobic bioprocesses by bioavailable essential trace metals.

PMID- 27690409
TI  - Photoelectrochemical Reduction of CO2 Coupled to Water Oxidation Using a
      Photocathode With a Ru(II)-Re(I) Complex Photocatalyst and a CoOx/TaON
      Photoanode.
AB  - Photoelectrochemical CO2 reduction activity of a hybrid photocathode, based on a
      Ru(II)-Re(I) supramolecular metal complex photocatalyst immobilized on a NiO
      electrode (NiO-RuRe) was confirmed in an aqueous electrolyte solution. Under half
      reaction conditions, the NiO-RuRe photocathode generated CO with high
      selectivity, and its turnover number for CO formation reached 32 based on the
      amount of immobilized RuRe. A photoelectrochemical cell comprising a NiO-RuRe
      photocathode and a CoOx/TaON photoanode showed activity for visible-light-driven
      CO2 reduction using water as a reductant to generate CO and O2, with the
      assistance of an external electrical (0.3 V) and chemical bias (0.10 V) produced
      by a pH difference. This is the first example of a molecular and semiconductor
      photocatalyst hybrid-constructed photoelectrochemical cell for visibl-light
      driven CO2 reduction using water as a reductant.

PMID- 27690410
TI  - Sub-stoichiometric Molybdenum Sulfide Phases with Catalytically Active Basal
      Planes.
AB  - Molybdenum sulfide (MoS2) is widely recognized for its catalytic activities where
      the edges of the crystals turn over reactions. Generating sulfur defects on the
      basal plane of MoS2 can improve its catalytic activity, but generally there is a
      lack of model system for understanding metal-centered catalysis on the basal
      planes. Here, we synthesized a new phase of sub-stoichiometric molybdenum sulfide
      (s-MoSx) on sulfur-enriched copper substrate. The basal plane of s-MoSx contains
      chemically reactive Mo-rich sites that can undergo dynamic dissociative
      adsorption/desorption processes with molecular hydrogen, thus demonstrating its
      usefulness for hydrogen-transfer catalysis. In addition, scanning tunneling
      microscopy was used to monitor surface-directed Ullmann coupling of 2,8-dibromo
      dibenzothiophene (DBDBT) molecules on s-MoSx nanosheets, where the four-fold
      symmetric surface sites on s-MoSx direct C-C coupling to form cyclic tetramers
      with high selectivity.

PMID- 27690411
TI  - Characterization of Indium Phosphide Quantum Dot Growth Intermediates Using MALDI
      TOF Mass Spectrometry.
AB  - Clusters have been identified as important growth intermediates during III-V
      quantum dot (QD) formation. Here we report a one-solvent protocol that integrates
      synthesis, purification and mass characterization of indium phosphide quantum dot
      growth mixtures. The use of matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometry (MS) successfully tracks the evolution of clusters and the
      formation of quantum dots throughout the synthesis. Similar clusters are observed
      during the formation of large particles, suggesting that these clusters serve as
      a reservoir for quantum dot formation. Combining MALDI and NMR techniques further
      enables us to extract extinction coefficients and construct sizing curves for
      cluster-free indium phosphide QDs. The use of MALDI MS opens new opportunities
      for characterization and mechanistic studies of small-sized air-sensitive
      clusters or QDs.

PMID- 27690412
TI  - Biosynthesis of Strained Piperazine Alkaloids - Uncovering the Concise Pathway of
      Herquline A.
AB  - Nature synthesizes many strained natural products that have diverse biological
      activities. Uncovering these biosynthetic pathways may lead to biomimetic
      strategies for organic synthesis of such compounds. In this work, we elucidated
      the concise biosynthetic pathway of herquline A, a highly strained and reduced
      fungal piperazine alkaloid. The pathway builds on a nonribosomal peptide
      synthetase de-rived di-tyrosine piperazine intermediate. Following enzymatic
      reduction of the P450-crosslinked di-cyclohexadienone, N-methylation of the
      piperazine serves as a trigger that leads to a cascade of stereoselective and
      nonenzymatic transformations. Computational analysis of key steps in the pathway
      rationalizes the observed reactivities.

PMID- 27690413
TI  - [MoO(S2)2L]1- (L = picolinate or pyrimidine-2-carboxylate) Complexes as MoSx
      Inspired Electrocatalysts for Hydrogen Production in Aqueous Solution.
AB  - Crystalline and amorphous molybdenum sulfide (Mo-S) catalysts are leaders as
      earth abundant materials for electrocatalytic hydrogen production. The
      development of a molecular motif inspired by the Mo-S catalytic materials and
      their active sites is of interest, as molecular species possess a great degree of
      tunable electronic prop-erties. Furthermore, these molecular mimics may be
      important for providing mechanistic insights towards the hydrogen evolution
      reaction (HER) with Mo-S electrocatalysts. Herein is presented two water soluble
      Mo-S complexes based around the [MoO(S2)2L2]1- motif. We present 1H-NMR spectra
      that reveal (NEt4)[MoO(S2)2picolinate] (Mo-pic) is stable in a d6-DMSO solution
      after heating at 100  degrees C, in air, revealing unprecedented thermal and
      aerobic stability of the homogenous electrocatalyst. Both Mo-pic and
      (NEt4)[MoO(S2)2pyrimidine-2-carboxylate] (Mo-pym) are shown to be homogenous
      electrocatalysts for the HER. The TOF of 27-34 s-1 and 42-48 s-1 for Mo-pic and
      Mo-pym and onset potentials of 240 mV and 175 mV for Mo-pic and Mo-pym
      respectively reveal these complexes as promising electrocatalysts for the HER.

PMID- 27690414
TI  - Urinary Clearance of Cranberry Flavonol Glycosides in Humans.
AB  - Cranberry is reported to have health benefits including prevention of urinary
      tract infections and other chronic diseases, due to the high content of
      polyphenols including flavonols and flavan-3-ols. The aim of this study was to
      determine the clearance of flavonol glycosides and flavan-3-ols and/or their
      metabolites in human urine. Ten healthy women volunteers ingested 240 ml
      cranberry juice containing flavonol glycosides. Urine samples were collected at
      0, 90, 225 and 360 minutes post-ingestion. While flavan-3-ols were not detected,
      five flavonol glycosides common in cranberry were identified. Quercetin-3
      galactoside, the most abundant cranberry flavonol, exhibited highest peak urine
      concentration (Cmax) of 1315 pg/mg creatinine, followed by quercetin-3
      rhamnoside, quercetin-3-arabinoside, myricetin-3-arabinoside and myricetin-3
      galactoside. Quercetin-3-arabinoside showed delayed clearance, Cmax at 237 min
      (Tmax), relative to other flavonols (90-151 min). Both aglycone and conjugated
      sugar moiety structure mediates the flavonol's bioavailability. Inter-individual
      variation for bioavailability and clearance is also apparent. Metabolites, e.g.
      glucoronides, were not detected.

PMID- 27690415
TI  - Effects of Sodium Chloride, Potassium Chloride and Calcium Chloride on the
      Formation of alpha-Dicarbonyl Compounds, Furfurals and Development of Browning in
      Cookies during Baking.
AB  - Effect of NaCl, KCl, CaCl2, NaHCO3, and NH4HCO3 on the formation of glucosone, 1
      deoxyglucosone, 3-deoxyglucosone, glyoxal, methylglyoxal, diacetyl, 5
      hydroxymethyl-2-furfural, 2-furfural and browning were investigated in cookies.
      Presence of 1.5% NaCl, 1% KCl, and 1% CaCl2 on flour basis had no effect on alpha
      dicarbonyl compounds, except 1-deoxyglucosone increased in the presence of KCl
      and CaCl2. The increase in 5-hydroxymethyl-2-furfural formation in the presence
      of NaCl, KCl, and CaCl2 did not relate to 3-deoxyglucosone formation and pH
      changes. NaCl, KCl, and CaCl2 increased browning in cookies. Model reaction
      systems indicated that NaCl, KCl, and CaCl2 enhance browning by increasing
      furfurals in caramelization. NaCl, KCl, and CaCl2 decreased browning intensity in
      heated glucose-glycine system. Usage of CaCl2 in cookies may considerably
      increase furfurals but not alpha-dicarbonyl compounds. Sodium reduction can be
      obtained by replacement with potassium without sacrificing the desired
      consequences of caramelization in sugar rich bakeries.

PMID- 27690416
TI  - 2-D Visualization of Nitrogen Distribution in Leaf of Chinese Cabbage (Brassica
      rapa Chinensis) by FTIR-PAS Technique.
AB  - Understanding nitrogen (N) status in the leaves of Chinese cabbage (Brassica rapa
      Chinensis) is of significance to both vegetable growth and quality control.
      Fourier transform infrared photoacoustic spectroscopy was used to perform rapid
      qualification of N distribution in leaf, a partial least squares algorithm was
      used to develop a model for prediction of N content, and N distribution in
      individual leaves was mapped based on interpolation analysis, which was found to
      be variable. A reasonable N input level (12 mmol L-1 N) showed the largest
      variance of N content, benefiting N redistribution and use efficiency, but
      variance decreased at old stage. Moreover, the pattern of N distribution within a
      leaf was irregular even among the replications performed for each treatment, and
      sunlight was found to be the dominant factor because of leaves receiving variable
      light intensities.

PMID- 27690417
TI  - Transcriptional Analysis of Stearoyl-Acyl Carrier Protein Desaturase Genes from
      Olive (Olea europaea) in Relation to the Oleic Acid Content of the Virgin Olive
      Oil.
AB  - The specific contribution of different stearoyl-ACP desaturase (SAD) genes to the
      oleic acid content in olive (Olea europaea) fruit has been studied. Towards that
      end, we isolated three distinct cDNA clones encoding three SAD isoforms from
      olive (cv. Picual), as revealed by sequence analysis. The expression levels of
      olive SAD genes were determined in different tissues from Picual and Arbequina
      cultivars, including developing mesocarp and seed, together with the unsaturated
      fatty acid content. Lipid and gene expression analysis indicate that OeSAD2 seems
      to be the main gene contributing to the oleic acid content of the olive fruit
      and, therefore, of the virgin olive oil. This conclusion was confirmed when the
      study was extended to Hojiblanca, Picudo and Manzanilla cultivars. Furthermore,
      our data indicate that the olive microsomal oleate desaturase gene OeFAD2-2, but
      not OeSAD2, is responsible for the linoleic acid content in the virgin olive oil.

PMID- 27690419
TI  - Overexpression of tomato Prosystemin (LePS) enhances pest resistance and the
      production of tanshinones in Salvia miltiorrhiza Bunge.
AB  - Tanshinones are a group of active diterpenes with pharmacological properties, are
      widely used in treatment of cardiovascular diseases. Jasmonate (JA) acts as an
      elicitor to enhance tanshinone biosynthesis in Salvia miltiorrhiza. However, due
      to high labor costs and undesirable chemical characteristics, the use of JA
      elicitation is still in the experimental stage. In our experiments,
      overexpression of Lycopersicon esculentum (tomato) Prosystemin (LePS) in
      transgenic plants of S. miltiorrhiza increased their JA concentrations,
      significantly enhanced productions of tanshinone, as well as activated the
      expression of key genes in the tanshinone biosynthesis pathway. Meanwhile, the
      relative levels of metabolites related to defense such as sterols, terpenes, and
      phenolic acids were also increased in our OEP lines. In addition, when the larvae
      of cotton bollworms (Heliothis armigera) were fed with leaves from transgenic
      lines, their mortality rates rose by nearly four-fold when compared with larvae
      exposed to leaves from the non-transformed wild type. Our study provides a new
      strategy for genetic engineering by which tanshinone production and pest
      resistance can be improved in S. miltiorrhiza. This is accomplished by simulating
      the wounding signal that increases endogenous levels of JA.

PMID- 27690418
TI  - Effect of Coffee in Lipopolysaccharide-Induced Indoleamine 2,3-Dioxygenase
      Activation and Depressive-like Behavior in Mice.
AB  - Research has identified a potential inverse correlation between coffee
      consumption and the risk of depression. The aim of this study was to investigate
      the effects of caffeinated coffee on lipopolysaccharide-induced depressive-like
      behaviors and inflammatory biomarkers in an in vivo model of depression in a
      C57BL/6J mouse model. The behavioral studies showed that caffeinated coffee
      decreased immobility time in both the tail suspension test (caffeinated coffee
      56.60 +/- 9.17; p < 0.0001) and the forced swimming test (caffeinated coffee
      28.80 +/- 5.93; p < 0.0001), suggesting antidepressant-like activity. The effects
      of caffeinated coffee on the inflammatory biomarkers associated with depression
      supported the results observed in the behavioral studies. Statistically
      significant decreases in indoleamine 2,3-dioxygenase activity (p < 0.001) and the
      neopterin/biopterin ratio (p < 0.001) were observed in animals pretreated with
      caffeinated coffee 24 h post-lipopolysaccharide exposure in comparison to the
      lipopolysaccharide control group. In conclusion, this study has provided evidence
      to suggest that caffeinated coffee has antidepressant-like activities; however,
      further studies are required to fully investigate these effects.

PMID- 27690421
TI  - Flexible Method for Conjugation of Phenol Lignin Model Compounds to Carrier
      Proteins.
AB  - Linking lignin model compounds to carrier proteins is required in order either to
      raise antibodies to them or to structurally screen antibodies raised against
      lignins or models. We describe a flexible method to link phenolic compounds of
      interest to cationic bovine serum albumin (cBSA) without interfering with their
      important structural features. With the guaiacylglycerol-beta-guaiacyl ether
      dimer, for example, the linking was accomplished in 89% yield with the number of
      dimers per carrier protein being as high as 50; NMR experiments on a 15N- and 13C
      labeled conjugation product indicated that 13 dimers were added to the native
      lysine residues and the remainder (~37) to the amine moieties on the
      ethylenediamine linkers added to BSA; ~32% of the available primary amine groups
      on cBSA were therefore conjugated to the hapten. This loading is suitable for
      attempting to raise new antibodies to plant lignins and for screening.

PMID- 27690420
TI  - New Broad-Spectrum Antibacterial Amphiphilic Aminoglycosides Active against
      Resistant Bacteria: From Neamine Derivatives to Smaller Neosamine Analogues.
AB  - Aminoglycosides (AGs) constitute a major family of potent and broad-spectrum
      antibiotics disturbing protein synthesis through binding to the A site of 16S
      rRNA. Decades of widespread clinical use of AGs strongly reduced their clinical
      efficacy through the selection of resistant bacteria. Recently, conjugation of
      lipophilic groups to AGs generated a novel class of potent antibacterial
      amphiphilic aminoglycosides (AAGs) with significant improved activities against
      various sensitive and resistant bacterial strains. We have identified amphiphilic
      3',6-dialkyl derivatives of the small aminoglycoside neamine as broad spectrum
      antibacterial agents targeting bacterial membranes. Here, we report on the
      synthesis and the activity against sensitive and resistant Gram-negative and/or
      Gram-positive bacteria of new amphiphilic 3',4'-dialkyl neamine derivatives and
      of their smaller analogues in the 6-aminoglucosamine (neosamine) series prepared
      from N-acetylglucosamine.

PMID- 27690422
TI  - Effects of engineered nanoparticles on the enantioselective transformation of
      metalaxyl agent and commercial metalaxyl in agricultural soils.
AB  - The adsorption coefficient of racemic metalaxyl onto an agriculture soil was
      small and non-enantioselective. Biotransformation was the predominant pathway for
      the elimination of R-metalaxyl, while abiotic and biotransformation made a
      comparable contribution to the degradation of S-metalaxyl. Metalaxyl acid was the
      main transformation intermediate. The enantiomer fraction of metalaxyl decreased
      with an increase in its initial spike concentration or the presence of the co
      constituents in metalaxyl commercial products. Under simulated solar irradiation,
      the presence of TiO2 promoted the overall transformation kinetics through
      enhanced biotransformation and extra photo-induced chemical reactions. The
      promotion was enantioselective and thereafter changed the enantiomer fraction.
      The results obtained in this study showed that some achiral parameters, although
      they have no direct impact on enantioselective reactions with enantiomers, can
      significantly affect the enantioselective transformation of racemic metalaxyl.
      Thus, our results indicate that the contribution of chemical interactions on the
      enantioselective transformation of chiral pesticides may be underestimated.

PMID- 27690424
TI  - Elucidation of Thermally Induced Changes in Key Odorants of White Mustard Seeds
      (Sinapis alba L.) and Rapeseeds (Brassica napus L.) Using Molecular Sensory
      Science.
AB  - Heat-processing of Brassica seeds led to the formation of a characteristic
      pleasant popcorn-like and coffee-like aroma impression compared to the mainly pea
      like aroma of the corresponding raw seeds. To analyze this phenomenon on a
      molecular basis, raw and roasted white mustard seeds and rapeseeds were analyzed
      using the sensomics approach. Application of comparative aroma extract dilution
      analysis (cAEDA) and identification experiments to raw and roasted (140  degrees
      C, 30 min) mustard seeds revealed 36 odorants (all identified for the first time)
      and 47 odorants (41 newly identified), respectively. Twenty-seven odorants in raw
      and 43 odorants in roasted (140  degrees C, 60 min) rapeseeds were found, which
      were all described for the first time. Among the set of volatiles, 2-isopropyl-3
      methoxypyrazine (earthy, pea-like) and 4-ethenyl-2-methoxyphenol (clove-like,
      smoky) showed high FD factors in both raw seeds. 4-Hydroxy-2,5-dimethylfuran
      3(2H)-one (caramel-like), 2,3-diethyl-5-methylpyrazine (earthy), dimethyl
      trisulfide (cabbage-like), and 2-acetyl-1-pyrroline (popcorn-like) were present
      at high flavor dilution (FD) factors in both roasted Brassica seeds. Odorants,
      differing in cAEDA or showing high FD factors in at least one of the seeds, were
      quantitated by stable isotope dilution analysis (SIDA), followed by the
      calculation of odor activity values (OAVs) using odor thresholds determined in
      refined sunflower oil. Eighteen aroma compounds in raw and 28 in roasted mustard
      seeds as well as 14 in raw and 25 in roasted rapeseeds revealed OAVs >=1. All
      four aroma recombinates, prepared by mixing the odorants showing OAVs >=1 in
      their naturally occurring concentrations, showed a very good similarity with the
      original seeds and, thus, proved the successful characterization of the
      respective key odorants.

PMID- 27690425
TI  - Antioxidant Properties of Heterocyclic Intermediates of the Maillard Reaction and
      Structural Related Compounds.
AB  - It is well established that a wide range of reductones is formed in the course of
      the Maillard reaction and that these substances contribute to the oxidative
      stability of food. The aim of this study was to analyze twelve important
      heterocyclic intermediates with and without reductone structure as well as
      structural related substances under equal conditions to compare their antioxidant
      properties in detail. For this purpose, five methods were selected including
      photometrical methods like the trolox equivalent antioxidant capacity assay and
      an electron paramagnetic resonance spectroscopic method. Reductones with furan-3
      one structure and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one were reducing
      in all assays while isomaltol and maltol did not react in assays based on the
      reduction of metal ions because of their complexing abilities. The introduction
      of protecting groups to the free hydroxyl functions of selected reductones could
      nearly eliminate their reducing abilities. In addition, the oxidation products of
      the different reductive heterocycles were compared after treatment with iodine.
      Mainly short-chained organic acids like lactic, glycolic and glyceric acid are
      formed as result of the degradation which indicate 1,3-dicarbonyl cleavage
      reactions of corresponding tricarbonyl compounds as intermediates of the
      oxidation.

PMID- 27690423
TI  - Effectiveness of FeEDDHA, FeEDDHMA, and FeHBED in Preventing Iron-Deficiency
      Chlorosis in Soybean.
AB  - The performance of FeHBED in preventing Fe deficiency chlorosis in soybean
      (Glycine max (L.) Merr.) in comparison to FeEDDHA and FeEDDHMA was studied, as
      well as the importance of the ortho-ortho and ortho-para/rest isomers in defining
      the performance. To this end, chlorophyll production (SPAD), plant dry matter
      yield, and the mass fractions of important mineral elements in the plant were
      quantified in a greenhouse pot experiment. All three Fe chelates increased SPAD
      index and dry matter yield compared to the control. The effect of FeHBED on
      chlorophyll production was visible over a longer time span than that of FeEDDHA
      and FeEDDHMA. Additionally, FeHBED did not suppress Mn uptake as much as the
      other Fe chelates. Compared to the other Fe chelates, total Fe content in the
      young leaves was lower in the FeHBED treatment; however, total Fe content was not
      directly related to chlorophyll production and biomass yield. For each chelate,
      the ortho-ortho isomer was found to be more effective than the other isomers
      evaluated.

PMID- 27690426
TI  - Synthesis, structure and spectroscopic properties of early transition metal
      .eta.2-iminoacyl complexes containing aryl oxide ligation.

PMID- 27690427
TI  - Discovery of Dihydrobenzoxazepinone (GS-6615) Late Sodium Current Inhibitor (Late
      INai), a Phase II Agent with Demonstrated Preclinical Anti-Ischemic and
      Antiarrhythmic Properties.
AB  - Late sodium current (late INa) is enhanced during ischemia by reactive oxygen
      species (ROS) modifying the Nav 1.5 channel, resulting in incomplete
      inactivation. Compound 4 (GS-6615, eleclazine) a novel, potent, and selective
      inhibitor of late INa, is currently in clinical development for treatment of long
      QT-3 syndrome (LQT-3), hypertrophic cardiomyopathy (HCM), and ventricular
      tachycardia-ventricular fibrillation (VT-VF). We will describe structure-activity
      relationship (SAR) leading to the discovery of 4 that is vastly improved from the
      first generation late INa inhibitor 1 (ranolazine). Compound 4 was 42 times more
      potent than 1 in reducing ischemic burden in vivo (S-T segment elevation, 15 min
      left anteriorior descending, LAD, occlusion in rabbits) with EC50 values of 190
      and 8000 nM, respectively. Compound 4 represents a new class of potent late INa
      inhibitors that will be useful in delineating the role of inhibitors of this
      current in the treatment of patients.

PMID- 27690428
TI  - 4-(((4-Iodophenyl)methyl)-4H-1,2,4-triazol-4-ylamino)-benzonitrile: A Potential
      Imaging Agent for Aromatase.
AB  - Aromatase (CYP19) is a rate-limiting enzyme that catalyzes the biosynthesis of
      estrogens. Imaging agents based on aromatase inhibitors (AIs) have been developed
      for a PET/SPECT study. A series of compounds was synthesized based on YM511,
      which has previously been used for breast cancer treatment. Two examples of these
      derivatives, 4-(((4-iodophenyl)methyl)-4H-1,2,4-triazol-4-yl-amino)-benzonitrile
      (5) and 4-((1H-imidazol-1-yl)(4-iodobenzyl)amino)benzonitrile (11), displayed
      potent binding affinities to human aromatase (IC50 = 0.17 and 0.04 nM,
      respectively). Biodistribution and autoradiographic studies revealed that [125I]5
      and [125I]11 were highly accumulated in the stomach (16.21 and 10.88% dose/g,
      respectively) and ovaries (8.56 and 3.32% dose/g, respectively) of female rats.
      Log P of [125I]5 was 2.49, meaning good brain penetration. Autoradiograms of
      brain sections showed a high uptake in the bed nucleus of the stria terminalis
      and amygdala. These results suggest that [125I]5 and [125I]11 are potent probes
      for aromatase imaging in both the brain and peripheral organs.

PMID- 27690429
TI  - New Inhibitors of Indoleamine 2,3-Dioxygenase 1: Molecular Modeling Studies,
      Synthesis, and Biological Evaluation.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive target for anticancer
      therapy. Herein, we report a virtual screening study which led to the
      identification of compound 5 as a new IDO1 inhibitor. In order to improve the
      biological activity of the identified hit, arylthioindoles 6-30 were synthesized
      and tested. Among these, derivative 21 exhibited an IC50 value of 7 MUM, being
      the most active compound of the series. Furthermore, compounds 5 and 21 induced a
      dose-dependent growth inhibition in IDO1 expressing cancer cell lines HTC116 and
      HT29. Three-dimensional quantitative structure-activity relationship studies were
      carried out in order to rationalize obtained results and suggest new chemical
      modifications.

PMID- 27690430
TI  - Side Chain Cyclized Aromatic Amino Acids: Great Tools as Local Constraints in
      Peptide and Peptidomimetic Design.
AB  - Constraining the conformation of flexible peptides is a proven strategy to
      increase potency, selectivity, and metabolic stability. The focus has mostly been
      on constraining the backbone dihedral angles; however, the correct orientation of
      the amino acid side chains (chi-space) that constitute the peptide pharmacophore
      is equally important. Control of chi-space utilizes conformationally constrained
      amino acids that favor, disfavor, or exclude the gauche (-), the gauche (+), or
      the trans conformation. In this review we focus on cyclic aromatic amino acids in
      which the side chain is connected to the peptide backbone to provide control of
      chi1- and chi2-space. The manifold applications for cyclized analogues of the
      aromatic amino acids Phe, Tyr, Trp, and His within peptide medicinal chemistry
      are showcased herein with examples of enzyme inhibitors and ligands for G protein
      coupled receptors.

PMID- 27690431
TI  - Sydnone Cycloaddition Route to Pyrazole-Based Analogs of Combretastatin A4.
AB  - The combretastatins are an important class of tubulin-binding agents. Of this
      family, a number of compounds are potent tumor vascular disrupting agents (VDAs)
      and have shown promise in the clinic for cancer therapy. We have developed a
      modular synthetic route to combretastatin analogs based on a pyrazole core
      through highly regioselective alkyne cycloaddition reactions of sydnones. These
      compounds show modest to high potency against human umbilical vein endothelial
      cell proliferation. Moreover, evidence is presented that these novel VDAs have
      the same mode of action as CA4P and bind reversibly to beta-tubulin, believed to
      be a key feature in avoiding toxicity. The most active compound from in vitro
      studies was taken forward to an in vivo model and instigated an increase in tumor
      cell necrosis.

PMID- 27690433
TI  - Oregonator Scaling Motivated by Showalter-Noyes Limit.
AB  - The Belousov-Zhabotinsky (BZ) reaction is the prototype oscillatory chemical
      system. We investigate here a new scaling of the Oregonator model of BZ chemical
      kinetics, and use this scaling to elucidate fundamental properties of BZ
      dynamics. In the Showalter-Noyes criterion for oscillation, that the product
      [H+][BrO3+] exceed a critical value, arises naturally as a critical value for a
      subcritical Hopf bifurcation in this setting, as does the reduction to a two
      variable model. We thus provide chemical explanations of the role of time scales
      in the BZ reaction.

PMID- 27690432
TI  - Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an
      Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986).
AB  - A novel series of second generation DPP1 inhibitors free from aorta binding
      liabilities found for earlier compound series was discovered. This work
      culminated in the identification of compound 30 (AZD7986) as a highly potent,
      reversible, and selective clinical candidate for COPD, with predicted human PK
      properties suitable for once daily human dosing.

PMID- 27690434
TI  - Passive Membrane Permeability in Cyclic Peptomer Scaffolds Is Robust to Extensive
      Variation in Side Chain Functionality and Backbone Geometry.
AB  - Synthetic and natural cyclic peptides provide a testing ground for studying
      membrane permeability in nontraditional drug scaffolds. Cyclic peptomers, which
      incorporate peptide and N-alkylglycine (peptoid) residues, combine the
      stereochemical and geometric complexity of peptides with the functional group
      diversity accessible to peptoids. We synthesized cyclic peptomer libraries by
      split-pool techniques, separately permuting side chain and backbone geometry, and
      analyzed their membrane permeabilities using the parallel artificial membrane
      permeability assay. Nearly half of the side chain permutations had permeability
      coefficients (Papp) > 1 * 10-6 cm/s. Some backbone geometries enhanced
      permeability due to their ability to form more stable intramolecular hydrogen
      bond networks compared with other scaffolds. These observations suggest that
      hexameric cyclic peptomers can have good passive permeability even in the context
      of extensive side chain and backbone variation, and that high permeability can
      generally be achieved within a relatively wide lipophilicity range.

PMID- 27690435
TI  - Discovery and Development of Kelch-like ECH-Associated Protein 1. Nuclear Factor
      Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction Inhibitors:
      Achievements, Challenges, and Future Directions.
AB  - The transcription factor Nrf2 is the primary regulator of the cellular defense
      system, and enhancing Nrf2 activity has potential usages in various diseases,
      especially chronic age-related and inflammatory diseases. Recently, directly
      targeting Keap1-Nrf2 protein-protein interaction (PPI) has been an emerging
      strategy to selectively and effectively activate Nrf2. This Perspective
      summarizes the progress in the discovery and development of Keap1-Nrf2 PPI
      inhibitors, including the Keap1-Nrf2 regulatory mechanisms, biochemical
      techniques for inhibitor identification, and approaches for identifying peptide
      and small-molecule inhibitors, as well as discusses privileged structures and
      future directions for further development of Keap1-Nrf2 PPI inhibitors.

PMID- 27690436
TI  - Coupled Electron-Nuclear Dynamics on H2+ Within Time-Dependent Born-Oppenheimer
      Approximation.
AB  - Quantum dynamical behaviour of H2+ in the presence of linearly polarized,
      ultrashort, intense, infrared laser pulse has been studied by numerically solving
      the time-dependent Schrodinger equation with nuclear motion restricted in one
      dimension along the direction of laser polarization and electronic motion in
      three-dimensions. Based on time-dependent Born-Oppenheimer approximation, we have
      constructed time-dependent potentials for the ground electronic state 1ssigmag of
      H2+. Subsequent nuclear dynamics is then carried out on these field-dressed
      potential energy surfaces and the dissociation dynamics is investigated. Our
      analysis reveal that although the electronic longitudinal degree of freedom plays
      the major role in governing the dissociation dynamics, contribution from the
      electronic transverse degree of freedom should also have to be taken into account
      in order to obtain accurate results. Also, modelling electron-nuclei Coulomb
      interaction in an one dimensional calculation with artificially chosen constant
      softening parameter leads to discrepancy with the exact results. Comparing our
      results with other quantum and classical dynamical studies showed a good
      agreement with exact results.

PMID- 27690437
TI  - Dynamic Behavior of Secondary Electrons in Liquid Water at the Earliest Stage
      upon Irradiation: Implications for DNA Damage Localization Mechanism.
AB  - To clarify the formation of radiation damage in DNA, the dynamic behavior of low
      energy secondary electrons produced by ionizing radiation in water was studied by
      using a dynamic Monte Carlo code that considers the Coulombic force between
      electrons and their parent cations. The calculated time evolution of the mean
      energy, total track length, and mean traveling distance of the electrons
      indicated that the prehydration of the electrons occurs competitively with
      thermalization on a timescale of hundreds of femtoseconds. The decelerating
      electrons are gradually attracted to their parent cations by Coulombic force
      within hundreds of femtoseconds, and finally about 12.6% electrons are
      distributed within 2 nm of the cations. The collision fraction for ionization and
      electronic excitation within 1 nm of the cation was estimated to be about 40%. If
      these electrons are decelerated in a living cell, they may cause highly localized
      lesions around a cation in a DNA molecule through additional dissociative
      electron transfer (DET) as well as ionization and electronic excitation (EXC),
      possibly resulting in cell death or mutation.

PMID- 27690438
TI  - IRMPD Spectroscopy of Metalated Flavins: Structure and Bonding of Lumiflavin
      Complexes with Alkali and Coinage Metal Ions.
AB  - Flavins are a fundamental class of biomolecules, whose photochemical properties
      strongly depend on their environment and their redox and metalation state.
      Infrared multiphoton dissociation (IRMPD) spectra of mass selected isolated metal
      lumiflavin ionic complexes (M+LF) are analyzed in the fingerprint range (800-1830
      cm-1) to determine the bonding of lumiflavin with alkali (M=Li, Na, K, Cs) and
      coinage (M=Cu, Ag) metal ions. The complexes are generated in an electrospray
      ionization source coupled to an ion cyclotron resonance mass spectrometer and the
      IR free electron laser FELIX. Vibrational and isomer assignments of the IRMPD
      spectra are accomplished by comparison to quantum chemical calculations at the
      B3LYP/cc-pVDZ level, yielding structure, binding energy, bonding mechanism, and
      spectral properties of the complexes. The most stable binding sites identified in
      the experiments involve metal bonding to the oxygen atoms of the two available CO
      groups of LF. Hence, CO stretching frequencies are a sensitive indicator of both
      the metal binding site and the metal bond strength. More than one isomer is
      observed for M=Li, Na, and K, and the preferred CO binding site changes with the
      size of the alkali ion. For Cs+LF only one isomer is identified although the
      energies of the two most stable structures differ by less than 7 kJ/mol. While
      the M+-LF bonds for alkali ions are mainly based on electrostatic forces,
      substantial covalent contributions lead to stronger bonds for the coinage metal
      ions. Comparison between lumiflavin and lumichrome reveals substantial
      differences in the metal binding motifs and interactions due to the different
      flavin structures.

PMID- 27690439
TI  - Synthesis of N-Alkenyl 2-Pyridonyl Ethers via a Au(I)-Catalyzed Rearrangement of
      2-Propargyloxypyridines.
AB  - N-Alkyl 2-pyridones and other enolizable heterocycles are important synthetic
      constructs, due to their prevalence in natural products and pharmaceutical
      targets and their capacity to serve as models for a number of biological and
      chemical processes. The disclosed Au(I)-catalyzed reaction utilizes 2
      propargyloxypyridines to access N-alkylated 2-pyridone products derived from both
      5-exo and 6-endo addition of the nitrogen to the pendent alkyne. Experimental and
      computational studies suggest that the desired 5-exo N-alkenyl 2-pyridonyl ethers
      are formed reversibly in the transformation. After extensive optimization, biaryl
      Au(I) catalyst 21 was found to overcome the inherent preference for the 6-endo
      pathway and provide the highest combination of 5-exo selectivity and yield.
      Herein, we report the application of this new Au(I)-catalyzed C-N bond formation
      to the preparation of a variety of N-alkenyl 2-pyridonyl ether analogues, which
      have the potential to serve as an entry point for the synthesis of complex N
      alkyl 2-pyridone-containing frameworks.

PMID- 27690440
TI  - Liquid-Assisted Grinding Accelerating: Suzuki-Miyaura Reaction of Aryl Chlorides
      under High-Speed Ball-Milling Conditions.
AB  - The effect of liquid-assisted grinding has been studied using mechanical Suzuki
      Miyaura reaction of aryl chlorides as the model reaction. Catalytic systems of
      Davephos and PCy3 are tested respectively showing strong influences from
      different liquids. Unexpected improvement of yield over 55% is observed using
      alcohols as additives, which is explained by in situ formed alkoxides and their
      participation in oxidative addition. Further expansion of substrates using
      Pd(OAc)2/PCy3/MeOH system gives desired products in good to high yields.

PMID- 27690441
TI  - DFT Mechanistic Study of Rh(III)-Catalyzed [3 + 2]/[5 + 2] Annulation of 4-Aryl
      1,2,3-triazoles and Alkynes Unveils the Dual C-H Activation Strategy.
AB  - Li and co-workers recently developed a dual C-H bond activation strategy, using a
      Rh(III) catalyst, for [3 + 2]/[5 + 2] annulation of primary 4-aryl-1,2,3
      triazoles and alkynes. The Rh(III)-catalyzed dual annulation of 4-aryl-1,2,3
      triazoles and alkynes is challenging because only single annulation is achieved
      using Rh(II) and Ni(0) catalysts. Intrigued by the novel strategy, we performed a
      density functional theory study to unravel this challenging dual C-H bond
      activation. A Friedel-Crafts type mechanism proved be more favorable than a
      concerted metalation-deprotonation (CMD) mechanism for the first C-H bond
      activation. The second C-H bond activation proceeded via a CMD mechanism. More
      importantly, the calculation explained why only AgSbF6, among several candidates,
      performed perfectly, whereas others failed, and why the dual annulation of 4-aryl
      1,2,3-triazoles with alkynes was achieved with a Rh(III) catalyst but not with
      Rh(II) and Ni(0) catalysts. Due to the active catalyst being [Cp*Rh(OAc)]+,
      AgSbF6, in which SbF6- is a stable anion, among several candidates performed
      perfectly. The success of the Rh(III)-catalyzed dual C-H bond activation has two
      origins: (i) the active catalyst [Cp*Rh(OAc)]+ is more stable than Cp*Rh(OAc)2
      when the Ag salt is AgSbF6, and this facilitates the first alkyne insertion; and
      (ii) a rhodium-carbene is easily formed.

PMID- 27690442
TI  - Aerobic Copper-Catalyzed Halocyclization of Methyl N-Heteroaromatics with
      Aliphatic Amines: Access to Functionalized Imidazo-Fused N-Heterocycles.
AB  - A new aerobic copper-catalyzed halocyclization reaction of methyl N
      heteroaromatics and aliphatic amines has been developed, which enables
      straightforward access to functionalized imidazo-fused N-heterocycles with the
      merits of good functional tolerance, use of easily available copper salts as the
      catalysts, lithium halides as the halogen sources, and O2 as a sole oxidant. Due
      to the reaction features' selective introduction of halogen functionalities to
      the newly formed imidazo ring, further extensions of the developed chemistry
      toward synthetic diversity, including effective access to functional materials,
      are easily envisioned.

PMID- 27690443
TI  - Variations in Rotational Barriers of Allyl and Benzyl Cations, Anions, and
      Radicals.
AB  - High accuracy quantum chemical calculations show that the barriers to rotation of
      a CH2 group in the allyl cation, radical, and anion are 33, 14, and 21 kcal/mol,
      respectively. The benzyl cation, radical, and anion have barriers of 45, 11, and
      24 kcal/mol, respectively. These barrier heights are related to the magnitude of
      the delocalization stabilization of each fully conjugated system. This paper
      addresses the question of why these rotational barriers, which at the Huckel
      level of theory are independent of the number of nonbonding electrons in allyl
      and benzyl, are in fact calculated to be factors that are of 2.4 and 4.1 higher
      in the cations and 1.5 and 1.9 higher in the anions than in the radicals. We also
      investigate why the barrier to rotation is higher for benzyl than for allyl in
      the cations and in the anions. Only in the radicals is the barrier for benzyl
      lower than that for allyl, as Huckel theory predicts should be the case. These
      fundamental questions in electronic structure theory, which have not been
      addressed previously, are related to differences in electron-electron repulsions
      in the conjugated and nonconjugated systems, which depend on the number of
      nonbonding electrons.

PMID- 27690444
TI  - Raman and IR Spectra of Ice Ih and Ice XI with an Assessment of DFT Methods.
AB  - IR and Raman spectroscopic technology can be directly used to identify the
      occurrence of ferroelectric ice XI in laboratory or extraterrestrial settings.
      The performance of 16 different DFT methods applied on the ice Ih, VIII, IX, and
      XI crystal phases are evaluated. Based on a selected DFT computational scheme,
      the IR and Raman spectra of ice Ih and XI are derived and compared. When
      comparing the spectra of ice Ih and ice XI, both IR and Raman, the librational
      vibrations are found to be the most affected by the proton ordering. The
      spectroscopic fingerprint of ice XI can be used to distinguish ferroelectric ice
      XI from ice Ih in the universe. Furthermore, the existence of only one kind of H
      bond in ice Ih is demonstrated from the overlapping sub-spectra for different
      types of H-bonded pair configurations in 16 isomers of ice Ih, which provides an
      illustration to the historic debate on whether one or two kinds of H-bonds
      existed in ice.

PMID- 27690445
TI  - A Chemical Activation Study of the Unimolecular Reactions of CD3CD2CHCl2 and
      CHCl2CHCl2 with Analysis of the 1,1-HCl Elimination Pathway.
AB  - Chemically activated C2D5CHCl2 molecules were generated with 88 kcal mol-1 of
      vibrational energy by the recombination of C2D5 and CHCl2 radicals in a room
      temperature bath gas. The competing 2,1-DCl and 1,1-HCl unimolecular reactions
      were identified by the observation of the CD3CD=CHCl and CD3CD=CDCl products. The
      initial CD3CD2C-Cl carbene product from 1,1-HCl elimination rearranges to
      CD3CD=CDCl under the conditions of the experiments. The experimental rate
      constants were 2.7 x107 and 0.47 x107 s-1 for 2,1-DCl and 1,1-HCl elimination
      reactions, respectively, which corresponds to branching fractions of 0.84 and
      0.16. The experimental rate constants were compared to calculated statistical
      rate constants to assign threshold energies of 54 and ~ 66 kcal mol-1 for the 1,2
      DCl and 1,1-HCl reactions, respectively. The statistical rate constants were
      obtained from models developed from electronic-structure calculations for the
      molecule and its transition states. The rate constant (5.3 x 107 s-1) for the
      unimolecular decomposition of CHCl2CHCl2 molecules formed with 82 kcal mol-1 of
      vibrational energy by the recombination of CHCl2 radicals also is reported. Based
      upon the magnitude of the calculated rate constant, 1,1-HCl elimination must
      contribute less than 15% to the reaction; 1,2-HCl elimination is the major
      reaction and the threshold energy is 59 kcal mol-1. Calculations also were done
      to analyze previously published rate constants for chemically activated CD2Cl
      CHCl2 molecules with 86 kcal mol-1 of energy in order to obtain a better overall
      description of the nature of the 1,1-HCl pathway for 1,1-dichloroalkanes. The
      interplay of the threshold energies for the 2,1-HCl and 1,1-HCl reactions and the
      available energy determines the product branching fractions for individual
      molecules. The unusual nature of the transition state for 1,1-HCl elimination is
      discussed.

PMID- 27690446
TI  - Molecular Recognition of tRNA with 1-Naphthyl Acetyl Spermine, Spermine and
      Spermidine: A Thermodynamic, Biophysical and Molecular Docking Investigative
      Approach.
AB  - A major thrust of anticancer therapeutics is the dynamic quest for small
      molecules that binds and modifies nucleic acids and proteins effectively. The
      role of tRNA in the protein translational machinery and the influence of
      polyamines on the interaction of acylated and deacylated tRNA to ribosomes,47-48
      make polyamine-tRNA interactions conspicuous. Therefore, we have studied the
      interaction of two biogenic polyamines spermine and spermidine with tRNAPhe and
      compared the interaction with the polyamine analog, 1-naphthyl acetyl spermine to
      fathom the thermodynamic and structural basis of the binding interaction. The
      binding affinity of spermine was comparable to 1-naphthyl acetyl spermine and
      both were greater than spermidine. The interactions led to significant thermal
      stabilization of the tRNAPhe and an increase in the enthalpy of transition. All
      the interactions were exothermic in nature and displayed prominent enthalpy
      entropy compensation behavior. The entropy driven nature of the interaction, the
      structural perturbations observed in circular dichroism spectra and docking
      results proved that the polyamines were bound in the groove of the anticodon arm
      of tRNAPhe. The amine groups in the polyamines were involved in extensive
      electrostatic, H-bonding and van der Waals interactions with the tRNAPhe
      molecule. The naphthyl group of 1-naphthyl acetyl spermine made additional
      stacking interaction with G24 and G26 of tRNAPhe, which was absent in the case of
      spermine and spermidine. Thus, the results demonstrate that the polyamine analog
      has a strong capability to target the same binding sites as biogenic polyamines
      but without substituting for the functions played by them, which may lead to
      exhibition of selective anti-cancer cytotoxicity. Therefore, this study on the
      interaction of 1-napthyl acetyl spermine with tRNAPhe potentiates further
      development of this analog as an anti-cancer therapeutic.

PMID- 27690447
TI  - Examining Ionic Liquid Effects on Mononuclear Rearrangement of Heterocycles using
      QM/MM Simulations.
AB  - The mononuclear rearrangement of heterocycles (MRH) reaction of the Z
      phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole into 4-benzoylamino-2,5
      diphenyl-1,2,3-triazole derives a sizable rate enhancement in the 1-butyl-3
      methylimidazolium tetrafluoroborate [BMIM][BF4] ionic liquid as compared to the
      hexafluorophosphate-based [BMIM][PF6] and conventional organic solvents. However,
      the origin of the rate difference between [BMIM][BF4] and [BMIM][PF6] has proven
      difficult to rationalize as no experimental trend relates the physical properties
      of the solvents, e.g., polarity and viscosity, to the rates of reaction. QM/MM
      calculations in combination with free-energy perturbation theory and Monte Carlo
      sampling have been carried out for the MRH reaction to elucidate the disparities
      in rates when using ionic liquids, methanol, and acetonitrile. Activation
      barriers and solute-solvent interactions have been computed for both an
      uncatalyzed and a specific base-catalyzed mechanism. Energetic and structural
      analyses determined that favorable pi+-pi interactions between the BMIM cation,
      the substrate phenyl rings, and the bicyclic quasi-aromatic 10pi
      oxadiazole/triazole transition state region imposed a pre-ordered geometric
      arrangement that enhanced the rate of reaction. An ionic liquid clathrate
      formation enforced a coplanar orientation of the phenyl rings that maximized the
      electronic effects exerted on the reaction route. In addition, site-specific
      electrostatic stabilization between the ions and the MRH substrate was more
      prevalent in [BMIM][BF4] as compared to [BMIM][PF6].

PMID- 27690448
TI  - Structural Basis of Tonic Inhibition by Dimers of Dimers in Hyperpolarization
      Activated Cyclic-Nucleotide-Modulated (HCN) Ion Channels.
AB  - The hyperpolarization-activated cyclic-nucleotide-modulated (HCN) ion channels
      control rhythmicity in neurons and cardiomyocytes. Cyclic AMP (cAMP) modulates
      HCN activity through cAMP-dependent formation of a tetrameric gating ring
      spanning the intracellular region (IR) of HCN. In the absence of cAMP, the IR
      cAMP-binding domain (CBD) mainly samples its inactive conformation, resulting in
      steric clashes that destabilize the IR tetramer. Although these clashes with the
      inactive CBD are released through tetramer dissociation into monomers, functional
      mutagenesis suggests that the apo IR is not fully monomeric. To investigate the
      inhibitory non-monomeric IR species, we performed molecular dynamics simulations
      starting from "hybrid" structures that are tetrameric, but contain inactive apo
      state CBD conformations. The ensemble of simulated trajectories reveals that full
      dissociation of the tetramer into monomers is not necessary to release the steric
      hindrance with the inactive CBD. Specifically, we found that partial dissociation
      of the tetramer into dimers is sufficient to accommodate four inactive CBDs,
      while reduction of the quaternary symmetry of the non-dissociated tetramer from
      four- to two-fold permits accommodation of two inactive CBDs. Our findings not
      only rationalize available electrophysiological, fluorometry and sedimentation
      equilibrium data, but they also provide unprecedented structural insight into
      previously elusive non-monomeric auto-inhibitory HCN species.

PMID- 27690449
TI  - Polarization of Gold in Nanopores Leads to Ion Current Rectification.
AB  - Biomimetic nanopores with rectifying properties are relevant components of ionic
      switches, ionic circuits, and biological sensors. Rectification indicates that
      currents for voltages of one polarity are higher than currents for voltages of
      the opposite polarity. Ion current rectification requires the presence of surface
      charges on the pore walls, achieved either by the attachment of charged groups,
      or in multi-electrode systems by applying voltage to integrated gate electrodes.
      Here, we present a simpler concept for introducing surface charges via
      polarization of a thin layer of Au present at one entrance of a silicon nitride
      nanopore. In an electric field applied by two electrodes placed in bulk solution
      on both sides of the membrane, the Au layer polarizes such that excess positive
      charge locally concentrates at one end and negative charge at the other end.
      Consequently, a junction is formed between zones with enhanced anion and cation
      concentrations in the solution adjacent to the Au layer. This bipolar double
      layer together with enhanced cation concentration in a negatively charged silicon
      nitride nanopore leads to voltage-controlled surface-charge patterns and ion
      current rectification. The experimental findings are supported by numerical
      modeling that confirm modulation of ionic concentrations by the Au layer and ion
      current rectification even in low-aspect ratio nanopores. Our findings enable a
      new strategy for creating ionic circuits with diodes and transistors.

PMID- 27690450
TI  - Correction to Synthesis of Bulk BC8 Silicon Allotrope by Direct Transformation
      and Reduced-Pressure Chemical Pathways.

PMID- 27690451
TI  - Targeting 24 bp within Telomere Repeat Sequences with Tandem Tetramer Pyrrole
      Imidazole Polyamide Probes.
AB  - Synthetic molecules that bind sequence-specifically to DNA have been developed
      for varied biological applications, including anticancer activity, regulation of
      gene expression, and visualization of specific genomic regions. Increasing the
      number of base pairs targeted by synthetic molecules strengthens their sequence
      specificity. Our group has been working on the development of pyrrole-imidazole
      polyamides that bind to the minor groove of DNA in a sequence-specific manner
      without causing denaturation. Recently, we reported a simple synthetic method of
      fluorescent tandem dimer polyamide probes composed of two hairpin moieties with a
      linking hinge, which bound to 12 bp in human telomeric repeats (5'-(TTAGGG)n-3')
      and could be used to specifically visualize telomeres in chemically fixed cells
      under mild conditions. We also performed structural optimization and extension of
      the target base pairs to allow more specific stain-ing of telomeres. In the
      present study, we synthesized tandem tetramer polyamides composed of four hairpin
      moieties, targeting 24 bp in telomeric repeats, the longest reported binding site
      for synthetic, non-nucleic-acid-based, sequence-specific DNA-binding molecules.
      The novel tandem tetramers bound with a nanomolar dissociation constant to 24 bp
      sequences made up of four telomeric repeats. Fluorescently labeled tandem
      tetramer polyamide probes could visualize human telomeres in chemically fixed
      cells with lower background signals than polyamide probes reported previously,
      suggesting that they had higher specificity for telomeres. Furthermore, high
      throughput sequencing of human genomic DNA pulled down by the biotin-labeled
      tandem tetramer polyamide probe confirmed its effective binding to telomeric
      repeats in the complex chromatinized genome.

PMID- 27690453
TI  - Surface Adsorption Energetics Studied with "Gold Standard" Wavefunction Based Ab
      Initio Methods: Small Molecule Binding to TiO2(110).
AB  - Coupled cluster theory with single, double and perturbative triple excitations
      (CCSD(T)) is widely considered to be the 'gold standard' of ab initio quantum
      chemistry. Using the domain-based pair natural orbital local correlation concept
      (DLPNO-CCSD(T)), these calculations can be performed on systems with hundreds of
      atoms at an accuracy of about 99.9% of the canonical CCSD(T) method. This allows
      for ab initio calculations providing reference adsorption energetics at solid
      surfaces with an accuracy approaching 1 kcal/mol. This is an invaluable asset,
      not least for the assessment of density-functional theory (DFT) as the prevalent
      approach for large-scale production calculations in energy or catalysis
      applications. Here we use DLPNO-CCSD(T) with embedded cluster models to compute
      entire adsorbate potential energy surfaces for the binding of a set of
      prototypical closed-shell molecules (H2O, NH3, CH4, CH3OH, CO2) to the rutile
      TiO2(110) surface. The DLPNO-CCSD(T) calculations show excellent agreement with
      available experimental data, even for the 'infamous' challenge of correctly
      predicting the CO2 adsorption geometry. The numerical efficiency of the approach
      is within one order of magnitude of hybrid-level DFT calculations, hence blurring
      the borders between reference and production technique.

PMID- 27690452
TI  - Quantitative Protein Sulfenic Acid Analysis Identifies Platelet Releasate-Induced
      Activation of Integrin beta2 on Monocytes via NADPH Oxidase.
AB  - Physiological stimuli such as thrombin, or pathological stimuli such as
      lysophosphatidic acid (LPA), activate platelets. The activated platelets bind to
      monocytes through P-selectin-PSGL-1 interactions but also release the contents of
      their granules, commonly called "platelet releasate". It is known that monocytes
      in contact with platelet releasate produce reactive oxygen species (ROS).
      Reversible cysteine oxidation by ROS is considered to be a potential regulator of
      protein function. In a previous study, we used THP-1 monocytic cells exposed to
      LPA- or thrombin-induced platelet releasate and a modified biotin switch assay to
      unravel the biological processes that are influenced by reversible cysteine
      oxidation. To gain a better understanding of the redox regulation of monocytes in
      atherosclerosis, we have now altered the modified biotin switch to selectively
      quantify protein sulfenic acid, a subpopulation of reversible cysteine oxidation.
      Using arsenite as reducing agent in the modified biotin switch assay, we were
      able to quantify 1161 proteins, in which more than 100 sulfenic acid sites were
      identified. Bioinformatics analysis of the quantified sulfenic acid sites
      highlighted the relevant, previously missed biological process of monocyte
      transendothelial migration, which included integrin beta2. Flow cytometry
      validated the activation of LFA-1 (alphaLbeta2) and Mac-1 (alphaMbeta2), two
      subfamilies of integrin beta2 complexes, on human primary monocytes following
      platelet releasate treatment. The activation of LFA-1 was mediated by ROS from
      NADPH oxidase (NOX) activation. Production of ROS and activation of LFA-1 in
      human primary monocytes were independent of P-selectin-PSGL-1 interaction. Our
      results proved the modified biotin switch assay to be a powerful tool with the
      ability to reveal new regulatory mechanisms and identify new therapeutic targets.

PMID- 27690454
TI  - Encapsulation and controlled release of rapamycin from polycaprolactone
      nanoparticles prepared by membrane micromixing combined with antisolvent
      precipitation.
AB  - Rapamycin loaded polycaprolactone nanoparticles (RAPA-PCL NPs) with a low
      polydispersity index of 0.006-0.073 were produced by anti-solvent precipitation
      using a ringed stainless steel membrane with 10-MUm diameter laser-drilled pores.
      The organic phase composed of 6 g L-1 of PCL and 0.6-3.0 g L-1 of RAPA in acetone
      was injected through the membrane at 140 L m-2 h-1 into 0.2 wt% aqueous polyvinyl
      alcohol solution stirred at 1300 rpm, resulting in a Z-average mean of 189-218
      nm, a drug encapsulation efficiency of 98.8-98.9 % and a drug loading in the NPs
      of 9-33 %. The encapsulation of RAPA was confirmed by UV-Vis spectroscopy, XRD,
      DSC, and ATR-FTIR. The disappearance of sharp characteristic peaks of crystalline
      RAPA in the XRD pattern of RAPA-PCL NPs revealed that the drug was molecularly
      dispersed in the polymer matrix or present in individual amorphous domains. The
      rate of drug release in pure water was negligible due to low aqueous solubility
      of RAPA. RAPA-PCL NPs released more than 91 % of their drug cargo after 2.5 h in
      the release medium composed of 0.78-1.5 M of the hydrotropic agent N,N
      diethylnicotinamide (DENA), 10 vol% of ethanol, and 2 vol% of Tween 20 in
      phosphate buffered saline. The release rate of RAPA was faster when the concentra
      tion of DENA in the dissolution medium was higher. The dissolution of RAPA was
      slower when the drug was embedded in the PCL matrix of the NPs than dispersed in
      the form of pure RAPA nanocrystals.

PMID- 27690456
TI  - Molecular organization of an adsorbed layer: a zwitterionic, pH-sensitive
      surfactant at the air/water interface.
AB  - Neutron and X-ray reflection measurements have been used to study the structure
      of the adsorbed layer of a chelating surfactant at the air/liquid interface. The
      chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (C12-DTPA) has a
      large head group containing eight donor atoms that can participate in the
      coordination of metal ions. The donor atoms are also titrating, resulting in an
      amphoteric surfactant that can adopt a number of differently charged species
      depending on the pH. Very strong coordination complexes are formed with metal
      ions, where the metal ion can be considered as part of the surfactant structure,
      in contrast to monovalent cations that act as regular counter-ions to the
      negative net charge. Adsorption was investigated over a large concentration
      interval, from well below the critical micelle concentration (cmc) to five times
      the cmc. The most striking result is the maximum in the surface excess found
      around the cmc, which is consistent with previous indications from surface
      tension measurements. Adding divalent metal ions has a limited effect on the
      adsorption at the air/liquid interface. The reason is the coordination of the
      metal ion, resulting in compensating deprotonation of the complex. Small
      variations in the head group area of different metal complexes are found,
      correlating to the conditional stability constants. Adding sodium chloride has a
      significant effect on the adsorption behavior and the results indicate that the
      protonation equilibrium is more important than the ionic strength effects. From
      combined fits of the neutron and X-ray data, a model that consists of a thick
      head group region and a relatively thin dehydrated tail region is found, and it
      indicates that the tails are not fully extended and that the limiting area per
      molecule is determined by the bulky head group.

PMID- 27690455
TI  - Tracking the Antibody Immunome in Type 1 Diabetes Using Protein Arrays.
AB  - We performed an unbiased proteome-scale profiling of humoral autoimmunity in
      recent-onset type 1 diabetes (T1D) patients and nondiabetic controls against ~10
      000 human proteins using a Nucleic Acid Programmable Protein Array (NAPPA)
      platform, complemented by a knowledge-based selection of proteins from genes
      enriched in human pancreas. Although the global response was similar between
      cases and controls, we identified and then validated six specific novel T1D
      associated autoantibodies (AAbs) with sensitivities that ranged from 16 to 27% at
      95% specificity. These included AAbs against PTPRN2, MLH1, MTIF3, PPIL2, NUP50
      (from NAPPA screening), and QRFPR (by targeted ELISA). Immunohistochemistry
      demonstrated that NUP50 protein behaved differently in islet cells, where it
      stained both nucleus and cytoplasm, compared with only nuclear staining in
      exocrine pancreas. Conversely, PPIL2 staining was absent in islet cells, despite
      its presence in exocrine cells. The combination of anti-PTPRN2, -MLH1, -PPIL2,
      and -QRFPR had an AUC of 0.74 and 37.5% sensitivity at 95% specificity. These
      data indicate that these markers behave independently and support the use of
      unbiased screening to find biomarkers because the majority was not predicted
      based on predicted abundance. Our study enriches the knowledge of the
      "autoantibody-ome" in unprecedented breadth and width.

PMID- 27690458
TI  - Correction to Highly Dense Cu Nanowires for Low-Overpotential CO2 Reduction.

PMID- 27690459
TI  - Improved Protein Conjugation with Uniform, Macroporous Poly(Acrylamide-co-Acrylic
      Acid) Hydrogel Microspheres via EDC/NHS Chemistry.
AB  - We demonstrate a robust and tunable micromolding method to fabricate chemically
      functional poly(acrylamide-co-acrylic acid) (p(AAm-co-AA)) hydrogel microspheres
      with uniform dimensions and controlled porous network structures for rapid
      biomacromolecular conjugation. Specifically, p(AAm-co-AA) microspheres with
      abundant carboxylate functional groups are fabricated via surface tension-induced
      droplet formation in patterned poly(dimethylsiloxane) (PDMS) molds and photo
      induced radical polymerization. To demonstrate chemical functionality, we
      enlisted a rapid EDC/NHS (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and
      N-hydroxysuccinimide (NHS)) chemistry for fluorescent labeling of the
      microspheres with a small molecule dye fluorescein glycine amide. Epifluorescence
      imaging results illustrate the uniform incorporation of carboxylate groups within
      the microspheres and rapid conjugation kinetics. Furthermore, protein conjugation
      results using red fluorescent protein R-phycoerythrin demonstrate highly porous
      nature of the microspheres as well as the utility of the microspheres and the
      EDC/NHS scheme for facile biomacromolecular conjugation. Combined, these results
      illustrate significant potential for our fabrication-conjugation strategy in the
      development of biofunctionalized polymeric hydrogel microparticles toward rapid
      biosensing, bioprocess monitoring, and biodiagnostics.

PMID- 27690457
TI  - Maximizing Headgroup Repulsion: Hybrid Surfactants with Ultrahighly Charged
      Inorganic Heads and Their Unusual Self-Assembly.
AB  - Nonequilibrium states of matter are arousing huge interest because of the
      outstanding possibilities to generate unprecedented structures with novel
      properties. Self-organizing soft matter is the ideal object of study as it
      unifies periodic order and high dynamics. Compared to settled systems, it becomes
      vital to realize more complex interaction patterns. A promising and intricate
      approach is implementing controlled balance between attractive and repulsive
      forces. We try to answer a fundamental question in surfactant science: How are
      processes like lyotropic liquid crystals and micellization affected, when
      headgroup charge becomes so large that repulsive interactions are inevitable? A
      particular challenge is that size and shape of the surfactant must not change. We
      could realize the latter by means of new hybrid surfactants with a
      heteropolyanion head [EW11O39]n- (E = PV, SiIV, BIII; n = 3, 4, 5). Among the
      unusual self-assembled structures, we report a new type of micelle with dumbbell
      morphology.

PMID- 27690461
TI  - Interactions of sulfobetaine zwitterionic surfactants with water on water
      surface.
AB  - We carried out a combined study using surface tension, phase-sensitive frequency
      generation (SFG) vibrational spectroscopy, and MD simulations to investigate the
      industrially-relevant zwitterionic surfactant N-dodecyl-N, N-dimethyl-3-ammonio-1
      propanesulfonate (DDAPS) on water surface. The SFG Im(chi(2)) spectra showed that
      the interaction between DDAPS and water was different from those between
      biologically-relevant zwitterionic phospholipids and water. While zwitterionic
      phospholipids were found to be anionic-like and flipped water molecules with
      their OHs pointing toward the air, DDAPS oriented water molecules with their OHs
      mostly pointing toward the liquid water. We built a new force field for the MD
      simulation which produced the correct surface tension of water with various DDPAS
      coverage. The MD simulation showed that the head groups of DDPAS were nearly
      parallel to the water surface. When the surface coverage of DDPAS was increased,
      the averaged tilting angle of DDPAS's tails decreased but it had little effect on
      the orientation of the head group. The sulfobetaine zwitterionic surfactant was
      found to be more cationic-like because the positively charged group was more
      capable of orienting interfacial water.

PMID- 27690460
TI  - Synthesis, in Vitro Evaluation, and Radiolabeling of Fluorinated Puromycin
      Analogues: Potential Candidates for PET Imaging of Protein Synthesis.
AB  - There is currently no ideal radiotracer for imaging of protein synthesis rate
      (PSR) by positron emission tomography (PET). Existing fluorine-18-labeled amino
      acid-based radiotracers predominantly visualize amino acid transporter processes,
      and in many cases they are not incorporated into nascent proteins at all. Others
      are radiolabeled with the short-half-life positron emitter carbon-11, which is
      rather impractical for many PET centers. Based on the puromycin (6) structural
      manifold, a series of 10 novel derivatives of 6 was prepared via Williamson ether
      synthesis from a common intermediate. A bioluminescence assay was employed to
      study their inhibitory action on protein synthesis, which identified the
      fluoroethyl analogue 7b as a lead compound. The fluorine-18 analogue was prepared
      via nucleophilic substitution of the corresponding tosylate precursor in a modest
      radiochemical yield of 2 +/- 0.6% with excellent radiochemical purity (>99%) and
      showed complete stability over 3 h at ambient temperature.

PMID- 27690462
TI  - Dielectric and Mechanical Investigations on the Hydrophilicity and Hydrophobicity
      of Polyethylene Oxide Modified on a Silicon Surface.
AB  - Polyethylene oxide (PEO) has been widely used in biomedical fields. The
      antibiofouling property of the PEO-modified surface has been extensively
      investigated but is far from being fully understood. A series of PEOs with
      narrowly distributed molecular weight (Mw), synthesized with the technique of
      high vacuum anionic polymerization, have been successfully grafted onto the
      surface of silicon wafers. The power-law relationship between the thickness of
      the monolayer versus the Mw of the grafted PEO shows a scaling of 0.3, indicating
      compact condensing of the chains. The static contact angles show higher
      hydrophobicity for the layer of PEO with higher Mw, which can be attributed to
      the closely packed conformation of the chains with high density. The frequency
      shift of the contact resonance indicates that the Young's modulus decreases and
      the loss factor increases with the increase in the Mw of PEO and the thickness of
      the PEO layers. Dielectric spectroscopy of bare or PEO-grafted wafers in the
      aqueous solutions reveals an interfacial polarization, which results from
      compositional and structural changes in the interface layer and depends on
      temperatures and salt concentrations. At a given grafting density, the PEO chains
      are swollen in pure water, demonstrating hydrophilic behavior, whereas they
      collapse in salt solutions, showing hydrophobic characteristics.

PMID- 27690463
TI  - Design and Synthesis of Orthogonally Protected d- and l-beta
      Hydroxyenduracididines from d-lyxono-1,4-Lactone.
AB  - A practical synthesis of the orthogonally protected d- and l-beta
      hydroxyenduracididines (d- and l-betahEnds), the unique, nonproteinogenic alpha
      amino acids found in mannopeptimycin antibiotics, is described. We appropriately
      applied d-lyxono-1,4-lactone derivatives as a starting template and investigated
      two transformations: (i) reduction of the lactone in a two-step sequence and (ii)
      regioselective ring opening of the benzylidene acetal. By careful evaluation of
      reaction conditions, multigram amounts of both orthogonally protected d- and l
      betahEnds were successfully prepared.

PMID- 27690464
TI  - Near Axisymmetric Partial Wetting Using Interface-Localized Liquid
      Dielectrophoresis.
AB  - The wetting of solid surfaces can be modified by altering the surface free energy
      balance between the solid, liquid, and vapor phases. Liquid dielectrophoresis (L
      DEP) can produce wetting on normally nonwetting surfaces, without modification of
      the surface topography or chemistry. L-DEP is a bulk force acting on the dipoles
      of a dielectric liquid and is not normally considered to be a localized effect
      acting at the interface between the liquid and a solid or other fluid. However,
      if this force is induced by a nonuniform electric field across a solid-liquid
      interface, it can be used to enhance and control the wetting of a dielectric
      liquid. Recently, it was reported theoretically and experimentally that this
      approach can cause a droplet of oil to spread along parallel interdigitated
      electrodes thus forming a stripe of liquid. Here we show that by using spiral
      shaped electrodes actuated with four 90 degrees  successive phase-shifted
      signals, a near axisymmetric spreading of droplets can be achieved. Experimental
      observations show that the induced wetting can achieve film formation, an effect
      not possible with electrowetting. We show that the spreading is reversible thus
      enabling a wide range of partial wetting droplet states to be achieved in a
      controllable manner. Furthermore, we find that the cosine of the contact angle
      has a quadratic dependence on applied voltage during spreading and deduce a
      scaling law for the dependence of the strength of the effect on the electrode
      size.

PMID- 27690465
TI  - Residual Silver Remarkably Enhances Electrocatalytic Activity and Durability of
      Dealloyed Gold Nanosponge Particles.
AB  - Percolation dealloying of multimetallic alloys entangles the selective
      dissolution of the less-noble elements with nanoscale restructuring of the more
      noble components, resulting in the formation of spongelike, nanoporous
      architectures with a unique set of structural characteristics highly desirable
      for heterogeneous catalysis. Although the dealloyed nanoporous materials are
      compositionally dominated by the more-noble elements, they inevitably contain
      residual less-noble elements that cannot be completely removed through the
      percolation dealloying process. How to employ the less-noble elements to
      rationally guide the structural evolution and optimize the catalytic performances
      of the dealloyed noble metal nanocatalysts still remains largely unexplored.
      Here, we have discovered that incorporation of Ag into Au-Cu binary alloy
      nanoparticles substantially enhances the Cu leaching kinetics while effectively
      suppressing the ligament coarsening during the nanoporosity-evolving percolation
      dealloying of the alloy nanoparticles. The controlled coleaching of Ag and Cu
      from Au-Ag-Cu ternary alloy nanoparticles provides a unique way to optimize both
      the surface area-to-mass ratios and specific activities of the dealloyed
      nanosponge particles for the electrocatalytic oxidation of alcohols. The residual
      Ag in the fully dealloyed nanosponge particles plays crucial roles in stabilizing
      the surface active sites and maintaining the nanoporous architectures during the
      electrocatalytic reactions, thereby greatly enhancing the durability of the
      electrocatalysts. The insights gained from this work shed light on the underlying
      roles of residual less-noble elements that are crucial to the rational
      optimization of electrocatalysis on noble-metal nanostructures.

PMID- 27690466
TI  - Catalytic Asymmetric Conjugate Addition of Carboxylic Acids via Oxa-Michael
      Reaction of Peroxy Hemiacetals followed by Kornblum DeLaMare Fragmentation.
AB  - Disclosed herein an overall methodology constitutes an equivalent to the long
      sought after enantioselective intramolecular oxa-Michael (IOM) reaction of
      carboxylic acids. An organocatalyzed IOM reaction of in situ formed peroxy
      hemiacetals followed by a Kornblum DeLaMare type rearrangement cascade provides a
      broad class of chiral lactones in good yields and with excellent
      enatioselectvities. Remarkably, the pure chiral lactones are obtained without any
      silica gel column chromatography, and in many cases, the enantioselectivity is
      further increased by a simple hexane wash of the isolated solid products.

PMID- 27690467
TI  - Stereocontrolled Synthesis of (+)-Plagiogyrin A.
AB  - Plagiogyrin A (1) was first isolated from the fronds of Plagiogyria matsumureana.
      Structurally, it features an alpha-ketoaldehyde functional group in its
      hemiacetal form, fused in a cis-substituted lactone ring. We have successfully
      synthesized the skeleton of this natural product by employing a stereocontrolled
      aldol reaction followed by the installation of the alpha-ketoaldehyde moiety
      derived from the mild oxidation of an alpha-diazoketone. Finally, anhydrous
      acidic conditions released the protected diol and provided the required cyclized
      hemiacetal.

PMID- 27690468
TI  - Probing the Interaction between a DNA Nucleotide (Adenosine-5'-Monophosphate
      Disodium) and Surface Active Ionic Liquids by Rotational Relaxation Measurement
      and Fluorescence Correlation Spectroscopy.
AB  - This article demonstrates the interaction of a deoxyribonucleic acid (DNA)
      nucleotide, adenosine-5'-monophosphate disodium (AMP) with a cationic surface
      active ionic liquid (SAIL) 1-dodecyl-3-methylimidazoium chloride (C12mimCl) and
      an anionic SAIL, 1-butyl-3-methylimidazolium n-octylsulfate ([C4mim][C8SO4]).
      Dynamic light scattering (DLS) measurements and 1H NMR (nuclear magnetic
      resonance) studies indicate that substantial interaction is taking place among
      the DNA nucleotide, AMP and the SAILs. Moreover, cryogenic transmission electron
      microscopy (cryo-TEM) suggests that SAILs containing micellar assemblies are
      transformed into larger micellar assemblies in presence of DNA nucleotide.
      Additionally, the rotational motion of two oppositely charged molecules,
      Rhodamine 6G perchlorate (R6G) and Fluorescein sodium salt (Fl-Na) have been
      monitored in these aggregates. The rotational motion of R6G and Fl-Na differs
      significantly between SAILs micelles, and SAILs-AMP containing larger micellar
      aggregates. The effect of negatively charged DNA nucleotide (AMP) addition into
      the cationic and anionic SAILs is more prominent for the cationic charged
      molecule R6G than that of anionic probe Fl-Na due to the favourable electrostatic
      interaction between the AMP and cationic R6G. Moreover, the influence of the
      anionic DNA nucleotide on the cationic and anionic SAIL micelles is monitored
      through the variation of the lateral diffusion motion of oppositely charged probe
      molecules (R6G and Fl-Na) inside these aggregates. This variation in diffusion
      coefficient values also suggests that interaction pattern of these oppositely
      charged probes are different within the SAILs-nucleotide containing aggregates.
      Therefore, both rotational and translational diffusion measurements confirm that
      the DNA nucleotide (AMP) renders more rigid microenvironment within the micellar
      solution of SAILs.

PMID- 27690469
TI  - A Reaction Valley Investigation of the Cycloaddition of 1,3-Dipoles with the
      Dipolarophiles Ethene and Acetylene - Solution of a Mechanistic Puzzle.
AB  - The reaction mechanism of the cycloaddition of ten 1,3-dipoles with the two
      dipolarphiles ethene and acetylene is investigated and compared using the unified
      reaction valley approach (URVA) in a new form, which is based on a dual level
      strategy, an accurate description of the reaction valley far out into the van der
      Waals region, and a comparative analysis of the electronic properties of the
      reaction complex. A detailed one-to-one compar- ison of 20 different 1,3-dipolar
      cycloadditions is carried out and so far unknown mechanistic features are
      revealed. There are significant differences in the reaction mechanisms for the
      two dipolarophiles that result from the van der Waals complex formation in the
      entrance channel of the cycloadditions. Hydrogen bonding between the 1,3-dipole
      and acetylene is generally stronger, which leads to higher reaction barriers in
      the acetylene case. Elementary differences are found with regard to charge
      transfer, charge polarization, rehybridization, and bond formation of the two
      dipolarophiles, which explain their different reaction energies. It is shown that
      similarities in the reaction barriers as determined by CCSD(T)-F12/aug-cc- pVTZ
      calculations are accidental because of a fortuitous cancellation of different
      electronic effects. In general, a caveat has to be made with regard to
      oversimplified descriptions of the reaction mechanism based on orbital theory or
      energy decomposition schemes.

PMID- 27690470
TI  - Guidelines to improve urticarial care and the remaining research gaps.

PMID- 27690471
TI  - Clinical practice guideline for diagnosis and management of urticaria.
AB  - Urticaria is a common skin condition that can compromise quality of life and may
      affect individual performance at work or school. Remission is common in majority
      of patients with acute spontaneous urticaria (ASU); however, in chronic cases,
      less than 50% had remission. Angioedema either alone or with urticaria is
      associated with a much lower remission rate. Proper investigation and treatment
      is thus required. This guideline, a joint development of the Dermatological
      Society of Thailand, the Allergy, Asthma, and Immunology Association of Thailand
      and the Pediatric Dermatological Society of Thailand, is graded and recommended
      based on published evidence and expert opinion. With simple algorithms, it is
      aimed to help guiding both adult and pediatric physicians to better managing
      patients who have urticaria with/without angioedema. Like other recent guideline,
      urticaria is classified into spontaneous versus inducible types. Patients present
      with angioedema or angioedema alone, drug association should be excluded, acetyl
      esterase inhibitors (ACEIs) and non-steroidal anti-inflammatory drugs (NSAIDs) in
      particular. Routine laboratory investigation is not cost-effective in chronic
      spontaneous urticaria (CSU), unless patients have clinical suggesting autoimmune
      diseases. Non-sedating H1-antihistamine is the first-line treatment for 2-4
      weeks; if urticaria was not controlled, increasing the dose up to 4 times is
      recommended. Sedating first-generation antihistamines have not been proven more
      advantage than non-sedating antihistamines. The only strong evidence-based
      alternative regimen for CSU is an anti-IgE: omalizumab; due to very high cost it
      however might not be accessible in low-middle income countries. Non
      pharmacotherapeutic means to minimize hyper-responsive skin are also important
      and recommended, such as prevention skin from drying, avoidance of hot shower,
      scrubbing, and excessive sun exposure.

PMID- 27690472
TI  - Avidity of selected autoantibodies - usefulness of their determination for
      clinical purposes.
AB  - Autoantibodies directed against various self-antigens comprise a heterogeneous
      group of immunoglobulins, which differ in their qualitative and quantitative
      features. An important qualitative characteristic of antibodies is
      affinity/avidity, which changes in the process of its maturation during the
      immune response.This study is aimed to summarize the knowledge about avidity of
      selected autoantibodies in certain autoimmune diseases. The avidity of various
      autoantibodies differs under distinct clinical situations. High-, moderate or low
      avidity may be found in biological fluids in patients with autoimmune
      diseases.The avidity maturation associated with progression from low to high
      values typical for antibodies against exogenous antigens is not always uniform in
      autoimmune diseases; therefore, the avidity of each autoantibody should be judged
      individually. Some studies promise the possible benefit of avidity examination
      for the refinement of diagnosis and prediction of selected autoimmune
      diseases.Key words: affinity - anti-citrullinated protein antibodies - anti
      glomerular basement membrane antibodies - anti-glutamate decarboxylase antibodies
      - anti-insulin antibodies - autoantibodies - avidity - onconeuronal antibodies.

PMID- 27690473
TI  - [The incidence of viral hepatitis A in the Hradec Kralove Region in the Czech
      Republic in the last decade].
AB  - OBJECTIVE: Viral hepatitis A continues to occur in the Czech Republic due to the
      high susceptibility of the population and existing opportunities for the
      transmission of the disease. The aim was to describe and analyse the incidence of
      viral hepatitis A in the Hradec Kralove Region in the Czech Republic in 2005
      2014, including the study of two outbreaks that required a different approach of
      field epidemiologists. MATERIAL AND METHODS: In 2015, a retrospective analysis
      was carried out of the data on the incidence of viral hepatitis A in Hradec
      Kralove Region in 2005-2014. The EPIDAT system where cases of infectious diseases
      and data from epidemiological investigations are reported was used as a data
      source for the purposes of the present analysis. In addition, two final reports
      on epidemic outbreaks of viral hepatitis A from 2014 were assessed. RESULTS: The
      incidence of viral hepatitis A at the regional level follows, to a certain
      extent, the pattern of the incidence of this disease at the national level. The
      highest number of cases was reported in 2010 due to a country-wide epidemic. The
      most affected age groups were children, adolescents, and young adults. The
      incidence of viral hepatitis A in individual years has a significant effect on
      the emergence of local outbreaks. CONCLUSION: The incidence of viral hepatitis A
      in the Czech Republic has a fluctuating trend, at both the national and regional
      levels. The highest incidence of viral hepatitis A was observed in the younger
      and middle-age categories. The high susceptibility of these population groups
      suggests the importance of vaccination against viral hepatitis A that confers
      specific personal protection.Key words: viral hepatitis A - incidence - outbreak 
      Czech Republic.

PMID- 27690474
TI  - [Effect of lipophosphonoxins on inhibition of bacterial colonization of bone
      cements].
AB  - OBJECTIVE: The study aimed at determining the ability of lipophosphonoxin DR5026
      to inhibit the formation of bacterial biofilm on the bone cement surface and
      assessing potential development of bacterial resistance. MATERIAL AND METHODS:
      Bone cement (Hi-Fatigue Bone Cement 2x40, aap Biomaterials GmbH, Germany) was
      polymerized with lipophosphonoxin DR5026. Cement samples were cultured using
      bacterial suspension containing Staphylococcus epidermidis CCM7221 at an inoculum
      density of 106 CFU/mL. After three, 24, and 48 hours of incubation at 35  degrees
      C, the number of bacteria adhered to the sample was measured and their growth
      curve was plotted. In 14 cycles, strains of Staphylococcus aureus, Enterococcus
      faecalis, Pseudomonas aeruginosa, and Streptococcus agalactiae were exposed to
      subinhibitory concentrations of DR5026 and the minimum inhibitory concentrations
      (MICs) were determined. RESULTS: After three hours of culture in the bacterial
      inoculum with an initial concentration of 106 CFU/mL, the number of colonies
      isolated from the cement sample treated with DR5026 was smaller by two orders of
      magnitude when compared to a control cement sample. After 24 and 48 hours of
      incubation, the number of CFU remained at 50 in the treated cement, whereas 109
      CFU were cultured from control cement samples. The plotted growth curves for
      bacteria adhered to cements clearly showed the inhibitory effect of
      lipophosphonoxin on their growth and multiplication, particularly after 48 hours.
      Following 14 cycles of repeated exposure to subinhibitory concentrations of
      DR5026, no increase in MICs was noted in the tested strains. CONCLUSION:
      Lipophosphonoxin DR5026 used to treat bone cement was found to have antibacterial
      effects and to inhibit the formation of bacterial biofilm. Repeated exposure of
      the tested bacteria to subinhibitory concentrations of the above lipophosphonoxin
      did not induce their resistance or increase their MICs.Key words: bone cement -
      joint replacement infections - lipophosphonoxins - antibacterial effect -
      biofilm.

PMID- 27690475
TI  - [Stenotrophomonas maltophilia as the cause of ventilator-associated pneumonia in
      a female patient with toxic epidermal necrolysis and Clostridium colitis: time
      for off-label tigecycline?]
AB  - Toxic epidermal necrolysis (TEN) is an autoimmune disease which is usually caused
      by a reaction to drugs. It affects mainly the skin and mucous membranes. It is a
      rare condition with a high mortality rate. Fatal outcomes in patients with TEN
      are mostly due to infectious complications. As antimicrobial drugs may induce
      this syndrome, the management of this condition is very complicated. Tigecycline
      is still a relatively new antibiotic approved in Europe for use in complicated
      intra-abdominal infections and complicated skin and soft tissue infections. Among
      major advantages of tigecycline in patients with TEN are its good penetrability
      into tissues, wide spectrum of activity that makes it suitable for use as
      monotherapy, and last but not least, in comparison with other antimicrobials, a
      very low potential for exacerbation of the severity of the underlying disease by
      further stimulation of the immune system. A case report is presented of a
      successful management of an 81-year-old woman with TEN and multiple infectious
      complications in different anatomic locations, the most serious of which was
      ventilator-associated pneumonia caused by Stenotrophomonas maltophilia. Her
      general condition was further aggravated by Clostridium colitis. Tigecycline was
      used as the therapeutic option for ventilator-associated pneumonia, although
      prescribed off-label.Key words: toxic epidermal necrolysis - tigecycline - off
      label indications - Clostridium colitis.

PMID- 27690476
TI  - The occurrence of Ixodes ricinus ticks and important tick-borne pathogens in
      areas with high tick-borne encephalitis prevalence in different altitudinal
      levels of the Czech Republic Part II. Ixodes ricinus ticks and genospecies of
      Borrelia burgdorferi sensu lato complex.
AB  - STUDY OBJECTIVE: Three years long research study (2011-2013) on population
      density of Ixodes ricinus and the infection rate of the pathogens that they
      transmit was conducted in four topographically distant areas in the Czech
      Republic. In the previous decade (2001-2010) thirteen loci with increased
      incidence of tick borne encephalitis cases were defined, suggesting the permanent
      interaction of human population with ticks and indicating the landmarks for study
      of the presence of other tick borne pathogens. The work program included the
      identification of existing spectrum of spirochetes from Borrelia burgdorferi
      sensu lato complex and the conditions of their occurrence and distribution.
      MATERIAL AND METHODS: In the areas of the Usti nad Labem Region, Olomouc Region,
      South Bohemian Region, and Highlands Region, 600 m2 plots were selected in the
      local optimal I. ricinus habitats where tick flagging was performed every year in
      the spring-summer and autumn seasons of the tick questing activity. Collected
      adult ticks (1369 males and 1404 females) were individually screened for B.
      burgdorferi s. l. spirochets. RESULTS: Spirochetes from B. burgdorferi s.l.
      complex were detected in all 13 studies sites in all altitudes from 280 to 1030
      meters a. s. l. The total rate of infection was determined as 11.4% (males 10.4%,
      females 12.4%) with range limits from 1.4% (Usti nad Labem in 2011) to 19.7%
      (South Bohemian Region, 2012).Genospecies were detected in various proportions
      and in different combinations: Borrelia afzelii, B. garinii, B. burgdorferi s.
      s., B. bavariensis, B. bissettii, B. valaisiana, B. spielmanii and B. lusitaniae.
      The three-year observation justifies the assumption that the regional differences
      in infectivity of I. ricinus are based on the character of the local biocenosis
      of the respective region. The dynamics of its seasonal changes, conditioned by
      climatic factors, determines the annual differences. CONCLUSION: Three of the
      medically most important Borrelia species formed a core group among all detected
      genospecies. B. afzelii was a dominated one (115 detections), followed by B.
      garinii (100) and by B. burgdorferi s.s. (19). Other genospecies were detected
      sporadically. However, the detection of B. bissettii should be emphasized due to
      the recently proven pathogenic effects of this genospecies and yet little-known
      sporadic expansion in the Czech Republic. The medical importance and distribution
      of other sporadically occurred genospecies is also discussed.Key words: Ixodes
      ricinus - Borrelia afzelii - B. garinii - B. burgdorferi s. s. - B. bavariensis -
      B. valaisiana - B. spielmanii - B. lusitaniae - B. bissettii - distribution -
      altitude - season - medical importance.

PMID- 27690477
TI  - Campylobacteriosis in the South Bohemian Region - a Recurrent Problem.
AB  - AIM: Campylobacteriosis is among the most frequently reported foodborne diseases
      in both the Czech Republic (CR) and South Bohemian Region (SBR).
      Campylobacteriosis has been a notifiable disease in the CR since 1984. The
      objective of this study is the analysis of the data reported to the surveillance
      system between 2005 and 2014 to describe the seasonal variation, age specific
      incidence, and route of transmission of campylobacteriosis in the South Bohemian
      Region. MATERIAL AND METHODS: The data reported to the surveillance system EPIDAT
      from 2005 to 2014 were analysed in order to determine the incidence trends and
      seasonality, age distribution, and route of transmission of campylobacteriosis in
      the South Bohemian Region. RESULTS: Campylobacteriosis incidence in the South
      Bohemian Region follows the same annual pattern as in the Czech Republic. There
      is a very slight declining trend in the incidence over the study period. A strong
      seasonal variation was observed, with a late summer peak and a winter low. An
      exception to the regularity of the incidence pattern was an outbreak notified in
      2010. The most affected age groups are children 1 to 5 years and newborns (0 age
      group). In the other age groups, the incidence has a declining tendency. The most
      common vehicles for the transmission of campylobacteriosis are chicken and meat
      products while other vehicles and routes of transmission have been reported
      exceptionally. CONCLUSION: Only one third of cases have been notified along with
      the suspected route of transmission. The most common route of transmission is
      through the consumption of contaminated chicken and meat, including smoked meat
      products. Therefore, the measures targeting consumers and also producers of
      poultry, meat, and unpasteurized milk products may contribute to the reduction of
      campylobacteriosis incidence.

PMID- 27690478
TI  - [HIV/AIDS epidemics in sub-Saharan regions in the 2010s: Regional analysis of
      UNAIDS data].
AB  - Of all HIV-positive people worldwide, more than two thirds live in Sub-Saharan
      Africa. Using updated data from UNAIDS, this article analyses whether there is
      still a signi-ficant increase in HIV in this region or whether national and
      international programmes and campaigns have successfully contributed to slowing
      down the epidemic or even reversing its trend. The historical context of the
      global pandemic of HIV/AIDS is discussed and regional specificities of the HIV
      spread in the UNAIDS African macro-regions are outlined. The issue of the key
      factors in the battle against HIV across the Sub-Saharan countries in the second
      decade of the 21st century is also considered.Key words: HIV/AIDS - Sub-Saharan
      Africa - regions - ART - history of the spread of HIV/AIDS - pandemics.

PMID- 27690479
TI  - Sleep quality affects cognitive functioning in returning combat veterans beyond
      combat exposure, PTSD, and mild TBI history.
AB  - OBJECTIVE: The purpose of this study was to determine how sleep quality affects
      cognitive functioning in returning combat veterans after accounting for effects
      of combat exposure, posttraumatic stress disorder (PTSD), and mild traumatic
      brain injury (mTBI) history. METHOD: This was a cross-sectional assessment study
      evaluating combat exposure, PTSD, mTBI history, sleep quality, and
      neuropsychological functioning. One hundred and nine eligible male
      Iraq/Afghanistan combat veterans completed an assessment consisting of a
      structured clinical interview, neuropsychological battery, and self-report
      measures. RESULTS: Using partial least squares structural equation modeling,
      combat experiences and mTBI history were not directly associated with sleep
      quality. PTSD was directly associated with sleep quality, which contributed to
      deficits in neuropsychological functioning independently of and in addition to
      combat experiences, PTSD, and mTBI history. Combat experiences and PTSD were
      differentially associated with motor speed. CONCLUSIONS: Sleep affected cognitive
      function independently of combat experiences, PTSD, and mTBI history. Sleep
      quality also contributed to cognitive deficits beyond effects of PTSD. An
      evaluation of sleep quality may be a useful point of clinical intervention in
      combat veterans with cognitive complaints. Improving sleep quality could
      alleviate cognitive complaints, improving veterans' ability to engage in
      treatment. (PsycINFO Database Record

PMID- 27690480
TI  - Helping employees sleep well: Effects of cognitive behavioral therapy for
      insomnia on work outcomes.
AB  - Drawing from recent research advances indicating the harmful effects of insomnia
      on negative affect, job satisfaction, self-control, organizational citizenship
      behavior, and interpersonal deviance, we hypothesized that treating insomnia with
      Internet based cognitive behavior therapy for insomnia would lead to improvements
      in these outcomes. In a field experiment with a randomized wait-list control
      group, we found that treatment had a beneficial direct effect on negative affect,
      job satisfaction, and self-control. Moreover, the effect of treatment on job
      satisfaction was mediated by negative affect. We were not able to detect a direct
      effect of treatment on organizational citizenship behavior or interpersonal
      deviance. However, treatment had a beneficial indirect effect on organizational
      citizenship behavior through the mediators of negative affect and job
      satisfaction, and a beneficial indirect effect on interpersonal deviance through
      the mediator of self-control. These results move the applied psychology
      literature on insomnia beyond simply pointing out problematic effects of employee
      insomnia to providing evidence of a partial solution to such effects. (PsycINFO
      Database Record

PMID- 27690481
TI  - Understanding diabetes and the role of psychology in its prevention and
      treatment.
AB  - Diabetes is a common, chronic, and costly condition that currently affects
      millions of individuals in the United States and worldwide with even greater
      numbers at high risk for developing the disease. Dramatic increases in diagnosed
      diabetes are projected for the decades to come meaning that most people will be
      affected by diabetes; either personally or through a family member. This article
      introduces the special issue of the American Psychologist focused on diabetes by
      providing an overview of the scope of diabetes and the importance of
      psychologists for improving disease management and quality of life. This includes
      an overview of the contributions of the behavioral and social sciences toward
      improved diabetes prevention and treatment. Finally, the article will point to
      opportunities for psychologists to close the gaps in the research, develop
      practice competencies, and increase training opportunities to meet the challenges
      of diabetes today and in the future.

PMID- 27690482
TI  - The social context of managing diabetes across the life span.
AB  - Diabetes self-management is crucial to maintaining quality of life and preventing
      long-term complications, and it occurs daily in the context of close
      interpersonal relationships. This article examines how social relationships are
      central to meeting the complex demands of managing Type I and Type 2 diabetes
      across the life span. The social context of diabetes management includes multiple
      resources, including family (parents, spouses), peers, romantic partners, and
      health care providers. We discuss how these social resources change across the
      life span, focusing on childhood and adolescence, emerging adulthood, and
      adulthood and aging. We review how diabetes both affects and is affected by key
      social relationships at each developmental period. Despite high variability in
      how the social context is conceptualized and measured across studies, findings
      converge on the characteristics of social relationships that facilitate or
      undermine diabetes management across the life span. These characteristics are
      consistent with both Interpersonal Theory and Self-Determination Theory, 2
      organizing frameworks that we utilize to explore social behaviors that are
      related to diabetes management. Involvement and support from one's social
      partners, particularly family members, is consistently associated with good
      diabetes outcomes when characterized by warmth, collaboration, and acceptance.
      Underinvolvement and interactions characterized by conflict and criticism are
      consistently associated with poor diabetes outcomes. Intrusive involvement that
      contains elements of social control may undermine diabetes management,
      particularly when it impinges on self-efficacy. Implications for future research
      directions and for interventions that promote the effective use of the social
      context to improve diabetes self-management are discussed. (PsycINFO Database
      Record

PMID- 27690485
TI  - Neurocognitive consequences of diabetes.
AB  - Mild cognitive dysfunction is a well-established complication of diabetes and its
      management, although large numbers of psychologists and health professionals may
      be unaware of its existence, clinical implications, and etiology. Drawing on
      results from key studies, systematic reviews, and meta-analyses, this article
      delineates the neurocognitive phenotypes characteristic of Type 1 diabetes (T1D)
      and Type 2 diabetes (T2D), and identifies the most plausible risk factors, both
      those that may be modifiable, like degree of metabolic control, and those that
      cannot be changed, like the age when a child or adult is diagnosed. Most children
      and adults with T1D typically manifest lower scores on measures of intelligence
      and academic achievement, attention, psychomotor speed, and executive functions.
      These effects are especially pronounced in those who develop diabetes early in
      life, before the age of 6 or 7 years. Chronically elevated blood glucose values
      increase the risk of both cognitive dysfunction and microstructural changes in
      white matter tracts. Adults with T2D manifest cognitive dysfunction characterized
      by poorer performance on tasks requiring attention, psychomotor speed, planning
      and executive functions, and learning and memory. They are also at increased risk
      of developing dementia. Poorer metabolic control accelerates the rate of
      cognitive decline over time, and research suggests that improving metabolic
      control may slow the rate of decline. Psychologists and behavioral scientists can
      play a key role in preventing the onset of cognitive complications or in
      ameliorating their severity by implementing behavioral strategies known to
      increase adherence to medical regimens and improve metabolic control. (PsycINFO
      Database Record

PMID- 27690483
TI  - Psychosocial factors in medication adherence and diabetes self-management:
      Implications for research and practice.
AB  - Diabetes is a chronic illness that places a significant self-management burden on
      affected individuals and families. Given the importance of health behaviors-such
      as medication adherence, diet, physical activity, blood glucose self-monitoring
      in achieving optimal glycemic control in diabetes, interventions designed and
      delivered by psychologists hold promise in assisting children, adolescents, and
      adults with diabetes in improving their health status and lowering their risk of
      serious complications. This article first provides an overview of diabetes self
      management and associated challenges and burdens. Socioeconomic status factors
      that may influence diabetes management and outcomes are briefly highlighted. We
      then review the evidence base for select psychosocial factors that may be
      implicated in diabetes self-management. Modifiable targets of psychological
      intervention are presented across 3 overarching domains: (a) knowledge, beliefs,
      and related cognitive constructs; (b) emotional distress and well-being; and (c)
      behavioral skills and coping. Important methodological issues facing future
      research are discussed, along with opportunities for psychologists in improving
      the care and treatment outcomes of individuals and families living with diabetes.
      In conclusion, we advocate for continued research emphasis on improving
      psychosocial aspects of living with diabetes, with greater attention to the
      situational context in which the self-regulatory processes underlying self
      management occur. Psychologists have important roles to play in reducing
      emotional distress, improving patient knowledge, and providing training in
      behavioral skills to promote successful self-management and to support patient
      centered diabetes care. (PsycINFO Database Record

PMID- 27690484
TI  - Psychological conditions in adults with diabetes.
AB  - Type 1 (T1D) and Type 2 diabetes (T2D) represent a demanding set of
      biopsychosocial challenges for patients and their families, whether the age of
      disease onset occurs in childhood, adolescence, or adulthood. Psychological
      conditions, defined as syndromes, disorders, and diabetes-specific psychological
      issues affect a larger proportion of individuals with T1D and T2D compared to the
      general population. In this review, we summarize the prevalence, impact and
      psychological treatments associated with the primary categories of psychological
      conditions that affect adults with T1D and T2D: depressive symptoms and
      syndromes, anxiety disorders, eating behaviors and disorders and serious mental
      illness. The implications of the literature for psychologists are discussed, and
      priorities for future research to advance the science of psychological conditions
      for adults with T1D and T2D are identified. (PsycINFO Database Record

PMID- 27690486
TI  - Psychology, technology, and diabetes management.
AB  - Use of technology in diabetes management is rapidly advancing and has the
      potential to help individuals with diabetes achieve optimal glycemic control.
      Over the past 40 years, several devices have been developed and refined,
      including the blood glucose meter, insulin pump, and continuous glucose monitor.
      When used in tandem, the insulin pump and continuous glucose monitor have
      prompted the Artificial Pancreas initiative, aimed at developing control system
      for fully automating glucose monitoring and insulin delivery. In addition to
      devices, modern technology, such as the Internet and mobile phone applications,
      have been used to promote patient education, support, and intervention to address
      the behavioral and emotional challenges of diabetes management. These state-of
      the-art technologies not only have the potential to improve clinical outcomes,
      but there are possible psychological benefits, such as improved quality of life,
      as well. However, practical and psychosocial limitations related to advanced
      technology exist and, in the context of several technology-related theoretical
      frameworks, can influence patient adoption and continued use. It is essential for
      future diabetes technology research to address these barriers given that the
      clinical benefits appear to largely depend on patient engagement and consistence
      of technology use. (PsycINFO Database Record

PMID- 27690488
TI  - Behavior change to prevent or delay Type 2 diabetes: Psychology in action.
AB  - Self-management is critical for the prevention and control of chronic health
      conditions. Research shows that dietary and physical activity behaviors related
      to obesity are inextricably linked to the development, course, and outcomes of
      Type 2 diabetes and its comorbidities. Therefore, a compelling case has been made
      for behavioral lifestyle intervention as the first-line approach. Academic
      psychologists and other behavioral scientists have contributed to all stages of
      obesity and diabetes prevention research and practice. They have made seminal
      contributions to the evidence-based science of health behavior change with the
      National Institutes of Health funded Diabetes Prevention Program randomized
      clinical trial and subsequent translation and dissemination efforts as exemplars.
      Beginning with social-cognitive learning theory and behavior modification for
      obesity, research psychologists have elucidated the critical elements associated
      with treatment efficacy and have demonstrated the benefits of identifying
      individuals at elevated risk and providing early intervention. Most often, the
      psychologist's role has been to design and evaluate programs based on behavioral
      principles, or supervise, train, and facilitate adherence to interventions,
      rather than function as the primary provider. Lifestyle interventions have made a
      strong public health impact, but pressing challenges remain. Issues include
      difficulties with long-term weight loss maintenance, heterogeneity of treatment
      response, pragmatic translation and dissemination concerns such as optimal
      training and delivery formats, scalability of lifestyle intervention programs,
      reimbursement, and a need for environmental and policy approaches that promote
      healthy lifestyle norms and behaviors for all communities. Health psychology
      should be at the forefront in addressing all of these concerns. (PsycINFO
      Database Record

PMID- 27690489
TI  - Evidence-based lifestyle interventions for obesity and Type 2 diabetes: The Look
      AHEAD intensive lifestyle intervention as exemplar.
AB  - The majority of individuals with Type 2 diabetes (T2D) are overweight or obese,
      and this excess adiposity negatively impacts cardiovascular risk and contributes
      to challenges in disease management. Treatment of obesity by behavioral lifestyle
      intervention, within the context of diabetes, produces broad and clinically
      meaningful health improvements, and recent studies demonstrate long-term
      sustained weight management success with behavioral lifestyle interventions.
      Details of the Look AHEAD intensive lifestyle intervention are provided as an
      exemplar approach to the secondary prevention of T2D and obesity. The presence of
      behavior change expertise in the development and delivery of evidence-based
      behavioral weight control is discussed, and issues of adaptation and
      dissemination are raised, with a model to guide these important steps provided.
      (PsycINFO Database Record

PMID- 27690487
TI  - Evidence-based behavioral interventions to promote diabetes management in
      children, adolescents, and families.
AB  - As members of multidisciplinary diabetes care teams, psychologists are well
      suited to support self-management among youth with Type 1 diabetes (T1D) and Type
      2 diabetes (T2D) and their families. Psychological and behavioral interventions
      can promote adherence to the complex and demanding diabetes care regimen, with
      the goals of promoting high quality of life, achieving optimal glycemic control,
      and ultimately preventing disease-related complications. This article reviews
      well-researched contemporary behavioral interventions to promote optimal diabetes
      family- and self-management and health outcomes in youth with T1D, in the context
      of key behavioral theories. The article summarizes the evidence base for
      established diabetes skills training programs, family interventions, and
      multisystemic interventions, and introduces emerging evidence for technology and
      mobile health interventions and health care delivery system interventions. Next
      steps in behavioral T1D intervention research include tailoring interventions to
      meet individuals' and families' unique needs and strengths, and systematically
      evaluating cost-effectiveness to advocate for dissemination of well-developed
      interventions. Although in its infancy, this article reviews observational and
      intervention research for youth with T2D and their families and discusses lessons
      for future research with this population. Interventions for youth with T2D will
      need to incorporate family members, consider cultural and family issues related
      to health behaviors, and take into account competing priorities for resources. As
      psychologists and behavioral scientists, we must advocate for the integration of
      behavioral health into routine pediatric diabetes care in order to effectively
      promote meaningful change in the behavioral and medical well-being of youth and
      families living with T1D and T2D. (PsycINFO Database Record

PMID- 27690490
TI  - Innovations in healthcare delivery and policy: Implications for the role of the
      psychologist in preventing and treating diabetes.
AB  - Although the biomedical model has dominated U.S. health care for more than a
      century, it has failed to adequately address current U.S. health care challenges,
      including the treatment and prevention of chronic disease; the epidemic rise in
      diabetes is one important example. In response, newer models of health care have
      been developed that address patients' mental and physical health concerns by
      multidisciplinary care teams that place the patient and family in the center of
      shared decision making. These new models of care offer many important
      opportunities for psychologists to play a larger role in the prevention and
      treatment of diabetes. However, for psychology's role to be fully realized, both
      external and internal challenges must be addressed. This will require
      psychologists to become more interdisciplinary, more familiar with the larger
      health care culture, more willing to expand their skill sets, and more
      collaborative with other health disciplines both from a patient-care and a larger
      advocacy perspective. (PsycINFO Database Record

PMID- 27690491
TI  - Phonological skills, visual attention span, and visual stress in developmental
      dyslexia.
AB  - In this study, we concurrently investigated 3 possible causes of dyslexia-a
      phonological deficit, visual stress, and a reduced visual attention span-in a
      large population of 164 dyslexic and 118 control French children, aged between 8
      and 13 years old. We found that most dyslexic children showed a phonological
      deficit, either in terms of response accuracy (92.1% of the sample), speed
      (84.8%), or both (79.3%). Deficits in visual attention span, as measured by
      partial report ability, affected 28.1% of dyslexic participants, all of which
      also showed a phonological deficit. Visual stress, as measured by subjective
      reports of visual discomfort, affected 5.5% of dyslexic participants, not more
      than controls (8.5%). Although phonological variables explained a large amount of
      variance in literacy skills, visual variables did not explain any additional
      variance. Finally, children with comorbid phonological and visual deficits did
      not show more severe reading disability than children with a pure phonological
      deficit. These results (a) confirm the importance of phonological deficits in
      dyslexia; (b) suggest that visual attention span may play a role, but a minor
      one, at least in this population; (c) do not support any involvement of visual
      stress in dyslexia. Among the factors that may explain some differences with
      previously published studies, the present sample is characterized by very
      stringent inclusion criteria, in terms of the severity of reading disability and
      in terms of exclusion of comorbidities. This may exacerbate the role of
      phonological deficits to the detriment of other factors playing a role in reading
      acquisition. (PsycINFO Database Record

PMID- 27690492
TI  - Children's processing and comprehension of complex sentences containing temporal
      connectives: The influence of memory on the time course of accurate responses.
AB  - In a touch-screen paradigm, we recorded 3- to 7-year-olds' (N = 108) accuracy and
      response times (RTs) to assess their comprehension of 2-clause sentences
      containing before and after. Children were influenced by order: performance was
      most accurate when the presentation order of the 2 clauses matched the
      chronological order of events: "She drank the juice, before she walked in the
      park" (chronological order) versus "Before she walked in the park, she drank the
      juice" (reverse order). Differences in RTs for correct responses varied by
      sentence type: accurate responses were made more speedily for sentences that
      afforded an incremental processing of meaning. An independent measure of memory
      predicted this pattern of performance. We discuss these findings in relation to
      children's knowledge of connective meaning and the processing requirements of
      sentences containing temporal connectives. (PsycINFO Database Record

PMID- 27690494
TI  - "Life-span development of visual working memory: When is feature binding
      difficult?": Correction to Cowan et al. (2006).
AB  - Reports an error in "Life-span development of visual working memory: When is
      feature binding difficult?" by Nelson Cowan, Moshe Naveh-Benjamin, Angela Kilb
      and J. Scott Saults (Developmental Psychology, 2006[Nov], Vol 42[6], 1089-1102).
      In the article, there were two errors in experiment 1a. The mean for color item
      information in older adults was incorrectly calculated. As a result, Figure 3
      shows a mean of over .70. The true mean was .63 (SEM=.04). This change diminishes
      the magnitude of the aging deficit for associative information, although this
      deficit still appears to remain, to a smaller extent. (For a conceptual
      replication see Peterson & Naveh-Benjamin, 2016). There also was an error in the
      experimental procedure of Experiment 1a. The older adults in that experiment
      received only half the number of trials specified in the methods section, and
      half as much as the other groups. For all groups, when there were 4 or 6 items
      and the probe was a binding change, the probed location was matched by the same
      color at 1 other location but, when there were 8 or 10 squares, the probed
      location was matched by the same color at 1, 2, or 3 other locations. For 8
      squares the number of trials was identical for these three trial subtypes
      whereas, for 10 squares, most of the trials had the same color at just 1 other
      location. These errors suggest that the experiment should be taken as only
      preliminary evidence that there is an aging deficit in color-location binding in
      visual working memory when color and binding trials are mixed in the same trial
      blocks. (The following abstract of the original article appeared in record 2006
      20488-009.) We asked whether the ability to keep in working memory the binding
      between a visual object and its spatial location changes with development across
      the life span more than memory for item information. Paired arrays of colored
      squares were identical or differed in the color of one square, and in the latter
      case, the changed color was unique on that trial (item change) or was duplicated
      elsewhere in the array (color-location binding change). Children (8-10 and 11-12
      years old) and older adults (65-85 years old) showed deficits relative to young
      adults. These were only partly simulated by dividing attention in young adults.
      The older adults had an additional deficiency, specifically in binding
      information, which was evident only when item- and binding-change trials were
      mixed together. In that situation, the older adults often overlooked the more
      subtle, binding-type changes. Some working memory processes related to binding
      undergo life-span development in an inverted-U shape, whereas other, bias- and
      salience-related processes that influence the use of binding information seem to
      develop monotonically.

PMID- 27690493
TI  - Children's and adults' interpretation of covariation data: Does symmetry of
      variables matter?
AB  - In a series of 3 experiments, the authors investigated the influence of symmetry
      of variables on children's and adults' data interpretation. They hypothesized
      that symmetrical (i.e., present/present) variables would support correct
      interpretations more than asymmetrical (i.e., present/absent) variables.
      Participants were asked to judge covariation in a series of data sets presented
      in contingency tables and to justify their judgments. Participants in Experiments
      1 and 2 were elementary school children (Experiment 1: n = 52 second graders, n =
      44 fourth graders; Experiment 2: n = 50 second graders). Participants in
      Experiment 3 were adults (n = 62). In Experiment 1, children in the symmetrical
      variables condition performed better than those in the asymmetrical variables
      condition. Children in the symmetrical variables condition judged more data
      patterns correctly and they more frequently justified their choices by referring
      to the complete table. Experiment 2 ruled out the possibility that this effect
      was caused by differences in question format. Even when question format was held
      constant, second graders performed better with symmetrical variables. Experiment
      3 showed that adults' data interpretation is also affected by symmetry of
      variables. Collectively, these results indicate that symmetry of variables
      affects interpretation of covariation data. The authors argue that symmetrical
      variables provide a context for meaningful comparison. With asymmetrical
      variables, the importance of the comparison is less salient. Thus, the symmetry
      of variables should be considered by researchers as well as educators. (PsycINFO
      Database Record

PMID- 27690495
TI  - Subjective and objective peer approval evaluations and self-esteem development: A
      test of reciprocal, prospective, and long-term effects.
AB  - A large body of literature suggests a clear, concurrent association between peer
      approval and self-esteem in adolescence. However, little empirical work exists on
      either the prospective or reciprocal relation between peer approval and self
      esteem during this age period. Moreover, it is unclear from past research whether
      both subjectively perceived peer approval and objectively measured peer approval
      are related to subsequent self-esteem over time (and vice versa) and whether
      these paths have long-term associations into adulthood. Using data from a large
      longitudinal study that covers a time span of 2 decades, we examined reciprocal,
      prospective relations between self-esteem and peer approval during ages 12-16 in
      addition to long-term relations between these variables and later social
      constructs at age 35. Cross-lagged regression analyses revealed small but
      persistent effect sizes from both types of peer approval to subsequent self
      esteem in adolescence, controlling for prior self-esteem. However, effects in the
      reverse direction were not confirmed. These findings support the notion that peer
      relationships serve an important function for later self-esteem, consistent with
      many theoretical tenets of the importance of peers for building a strong
      identity. Finally, we found long-term relations between adult social constructs
      and adolescent objective and subjective peer approval as well as self-esteem.
      Therefore, not only do peer relationships play a role in self-esteem development
      across adolescence, but they remain impactful throughout adulthood. In sum, the
      current findings highlight the lasting, yet small link between peer relationships
      and self-esteem development and call for investigations of further influential
      factors for self-esteem over time. (PsycINFO Database Record

PMID- 27690496
TI  - Early child care and adolescent functioning at the end of high school: Results
      from the NICHD Study of Early Child Care and Youth Development.
AB  - Relations between early child care and adolescent functioning at the end of high
      school (EOHS; M age = 18.3 years) were examined in a prospective longitudinal
      study of 1,214 children. Controlling for extensive measures of family background,
      early child care was associated with academic standing and behavioral adjustment
      at the EOHS. More experience in center-type care was linked to higher class rank
      and admission to more selective colleges, and for females to less risk taking and
      greater impulse control. Higher quality child care predicted higher academic
      grades and admission to more selective colleges. Fewer hours in child care was
      related to admission to more selective colleges. These findings suggest long-term
      benefits of higher quality child care, center-type care, and lower child-care
      hours for measures of academic standing at the EOHS. (PsycINFO Database Record

PMID- 27690497
TI  - Effects of the interparental relationship on adolescents' emotional security and
      adjustment: The important role of fathers.
AB  - We examined the mediational roles of multiple types of adolescents' emotional
      security in relations between multiple aspects of the interparental relationship
      and adolescents' mental health from ages 13 to 16 (N = 392). General marital
      quality, nonviolent parent conflict, and physical intimate partner violence
      independently predicted mental health. Security in the father-adolescent
      relationship, over and above security with the mother and security in regard to
      parent conflict, mediated the link from general marital quality to adolescents'
      mental health. With 2 exceptions, paths were stable for boys and girls,
      biological- and stepfathers, and Anglo- and Mexican Americans. The findings
      reveal the need to expand the traditional foci on parent conflict and
      relationships with mothers to include general marital quality and relationships
      with fathers. (PsycINFO Database Record

PMID- 27690498
TI  - "Temporal attitudes profile transition among adolescents: A longitudinal
      examination using mover-stayer latent transition analysis": Correction to Morgan
      et al. (2016).
AB  - Reports an error in "Temporal attitudes profile transition among adolescents: A
      longitudinal examination using mover-stayer latent transition analysis" by Grant
      B. Morgan, Kevin E. Wells, James R. Andretta and Michael T. McKay (Psychological
      Assessment, Advanced Online Publication, Sep 5, 2016, np). In the article, the
      affiliation for Michael T. McKay should be Department of Psychological Sciences,
      University of Liverpool. All versions of this article have been corrected. (The
      following abstract of the original article appeared in record 2016-42727-001.)
      Over the last 20 years, the study of Temporal Psychology and its relationship
      with a range of psychosocial indicators has increased exponentially. The present
      study makes use of recent advances in analytic methods and uses statistical
      inference via longitudinal examination of latent profiles through Latent
      Transition Analyses (LTA). The first 2 available waves of data from a
      longitudinal study in the United Kingdom were used to assess the following: (a)
      the factor structure of Adolescent Time Inventory-Time Attitudes Scale (ATAS)
      scores at Waves 1 and 2, (b) the viability of time attitudes profiles based on
      ATAS scores at both time points, (c) the degree of stability and/or transition
      between membership of these profiles at +12 months, and (d) the relationship
      between profiles and scores on 4 distal outcomes, including academic, social and
      emotional self-efficacy, and sensation seeking. Four latent profiles called
      Positives, Ambivalents, Negatives, and Negative-Futures were identified and their
      relationship with the 4 distal outcomes was examined. Results showed that time
      attitude profiles were unstable across the first year of high school.
      Furthermore, instability was explained by transitions to more negative profiles,
      and these transitions were associated with unfavorable outcomes. (PsycINFO
      Database Record

PMID- 27690499
TI  - Positive family relationships: Longitudinal network of relations.
AB  - The construct of positive family relationships (PFR), defined as family members
      getting along well and supporting each other, was investigated in a long-term
      prospective study. A newly constructed scale of positive family relationships
      developed using the nominal response model of item-response theory, was subject
      to a longitudinal network of relations analysis. The conceptualization for this
      research was founded on a positive psychology framework. Data derived from the
      Fullerton Longitudinal Study and spanned 20 years from middle childhood (age 9
      years) to early adulthood (age 29 years). Evidence indicated both stability and
      change in PFR across time. Moderate to high stability of individual differences
      among families across 9 annual assessments was found from ages 9-17 years.
      Concomitantly across these years, there was a progressive decline in PFR. PFR
      proved to be independent of socioeconomic status. Specific conceptually based
      directional hypotheses were tested using structural equation modeling. Multiple
      sources of information included intra- and cross-informant, as well as objective
      and ecologically valid data. The network of relations involved concurrent and
      predictive criterion-related variables. PFR had a pervasive relation to a variety
      of psychological domains across time. As predicted, PFR related (a) positively to
      family cohesion and inversely to family conflict, (b) positively to parental
      social support, (c) positively to children's self-concept, (d) positively to
      children's academic performance and educational attainment, and (e) inversely to
      children's behavior problems. The theoretical importance of the findings and the
      applicability of the PFR Scale for both researchers and practitioners in the
      field of family psychology are discussed. (PsycINFO Database Record

PMID- 27690500
TI  - Dyadic effects of resilience on well-being in Chinese older couples: Mediating
      role of spousal support.
AB  - Concerning the interdependence of married couples, the strengths of not only
      actors but also of partners might improve aging successfully. This study aimed to
      examine the actor and partner effects of resilience on well-being in Chinese
      older couples and the potential mediating role of spousal exchanges at the actor
      and partner levels. Using a 2-wave longitudinal design, a total of 158 Chinese
      couples (age range 60-97 years) completed measures of resilience, perceived
      spousal exchanges (spousal support and negative exchanges), and well-being. The
      results showed that (a) the dyad had significant congruence in resilience and
      well-being, respectively; (b) resilience had significant actor and partner
      effects on well-being within the dyad; and (c) negative spousal exchanges could
      not mediate the actor and partner effects of resilience on well-being, and a
      gender difference emerged for the mediation role of spousal support: Actor and
      partner effects of husbands' resilience on well-being were mediated by both
      partners' perceived spousal support, whereas the actor and partner effects of
      wives' resilience on well-being were not mediated by perceived spousal support.
      Focusing on couples' interdependence, this study highlighted the role of spousal
      resilience and support on successful aging. Interventions should focus on
      enhancing both partners' resilience and promoting mutual support within the
      couple. (PsycINFO Database Record

PMID- 27690501
TI  - Alternative and complementary reinforcers as mechanisms linking adolescent
      conduct problems and substance use.
AB  - The present study tested the hypothesis that teens who engage in conduct problems
      are more likely to use substances because they engage in fewer alternative
      reinforcing (i.e., pleasurable) substance-free activities and more complementary
      reinforcing substance-associated activities. In a cross-sectional, correlational
      design, 9th grade students (N = 3,383; mean age = 14.6 years) in Los Angeles,
      California, U.S.A. completed surveys in 2013 measuring conduct problems (e.g.,
      stealing, lying, getting in fights); alternative and complementary reinforcement;
      use of a number of licit, illicit, and prescription drugs; and other cofactors.
      Conduct problems were positively associated with past 6-month use of any
      substance (yes/no) among the overall sample and past 30-day use frequency on a
      composite index that included 6 substances among past 6-month users. These
      associations were statistically mediated by diminished alternative reinforcement
      and increased complementary reinforcement when adjusting for relevant covariates.
      Conduct problems were associated with lower engagement in alternative reinforcers
      and increased engagement in complementary reinforcers, which, in turn, were
      associated with greater likelihood and frequency of substance use. Most
      mediational relations persisted adjusting for demographic, environmental, and
      intrapersonal cofactors and generalized to alcohol, cigarette, and marijuana use,
      although, complementary reinforcers did not significantly mediate the relation of
      conduct problems with alcohol use frequency. These results point to diminished
      alternative reinforcement and increased complementary reinforcement as mechanisms
      linking conduct problems and adolescent substance use. Interventions that
      increase access to and engagement in a diverse set of alternative substance-free
      activities and deter activities that complement use may prevent substance use in
      adolescents who engage in conduct problems. (PsycINFO Database Record

PMID- 27690502
TI  - Acute and chronic effects of cannabidiol on Delta9-tetrahydrocannabinol (Delta9
      THC)-induced disruption in stop signal task performance.
AB  - Recent clinical and preclinical research has suggested that cannabidiol (CBD) and
      Delta9-tetrahydrocannabinol (Delta9-THC) have interactive effects on measures of
      cognition; however, the nature of these interactions is not yet fully
      characterized. To address this, we investigated the effects of Delta9-THC and CBD
      independently and in combination with proposed therapeutic dose ratios of 1:1 and
      1:3 Delta9-THC:CBD in adult rhesus monkeys (n = 6) performing a stop signal task
      (SST). Additionally, the development of tolerance to the effects of Delta9-THC on
      SST performance was evaluated by determining the effects of acutely administered
      Delta9-THC (0.1-3.2 mg/kg), during a 24-day chronic Delta9-THC treatment period
      with Delta9-THC alone or in combination with CBD. Results indicate that Delta9
      THC (0.032-0.32 mg/kg) dose-dependently decreased go success but did not alter go
      reaction time (RT) or stop signal RT (SSRT); CBD (0.1-1.0 mg/kg) was without
      effect on all measures and, when coadministered in a 1:1 dose ratio, did not
      exacerbate or attenuate the effects of Delta9-THC. When coadministered in a 1:3
      dose ratio, CBD (1.0 mg/kg) attenuated the disruptive effects of 0.32 mg/kg
      Delta9-THC but did not alter the effects of other Delta9-THC doses. Increases in
      ED50 values for the effects of Delta9-THC on SST performance were apparent during
      chronic Delta9-THC treatment, with little evidence for modification of changes in
      sensitivity by CBD. These results indicate that CBD, when combined with Delta9
      THC in clinically available dose ratios, does not exacerbate and, under
      restricted conditions may even attenuate, Delta9-THC's behavioral effects.
      (PsycINFO Database Record

PMID- 27690504
TI  - The role of past interactions in great apes' communication about absent entities.
AB  - Recent evidence suggests that great apes can use the former location of an entity
      to communicate about it. In this study we built on these findings to investigate
      the social-cognitive foundations of great apes' communicative abilities. We
      tested whether great apes (n = 35) would adjust their requests for absent
      entities to previous interactions they had with their interlocutor. We
      manipulated the apes' experience with respect to the interlocutor's knowledge
      about the previous content of the now-empty location as well as their experience
      with the interlocutor's competence to provide additional food items. We found
      that apes adjusted their requests to both of these aspects but failed to
      integrate them with one another. These results demonstrate a surprising amount of
      flexibility in great apes' communicative abilities while at the same time
      suggesting some important limitations in their social communicative skills.
      (PsycINFO Database Record

PMID- 27690503
TI  - Use of an automated mobile application to assess effects of nicotine withdrawal
      on verbal fluency: A pilot study.
AB  - Mild-to-moderate impairment in frontally mediated functions such as sustained
      attention, working memory, and inhibition have been found to occur during tobacco
      withdrawal and may present a barrier to successful cessation. These findings have
      led to studies evaluating cessation treatments that target nicotine withdrawal
      related cognitive impairment. The instruments currently used to assess cognitive
      function provide detailed and specific information but have limitations including
      being time consuming, cumbersome, anxiety provoking, and having poor ecological
      validity. The authors examined the feasibility of using a mobile computer
      application to test verbal fluency (VF) as a quick, easy-to-administer, and more
      ecologically valid method of measuring the effects of short-term smoking
      abstinence on frontally mediated cognitive functions. Thirty participants
      completed 2 assessments-1 during ad lib smoking and 1 after overnight abstinence.
      At each assessment, semantic and phonemic VF tests were administered using a
      mobile application and nicotine craving and withdrawal symptom severity was
      assessed. In repeated assessments, performance on both semantic and phonemic VF
      tests is expected to improve due to practice effects; however, significant
      improvements were observed only in semantic (p = .012) but not phonemic (p =
      .154) VF. In addition, the change between assessments in phonemic (but not
      semantic) score was significantly associated with withdrawal (p = .006) and
      craving (p = .037) severity measured postabstinence. This study demonstrates that
      nicotine withdrawal has differential effects on semantic versus phonemic VF
      suggesting impairments of working memory, attention, and inhibition. These
      effects were measured using methods easily used in large groups of participants,
      potentially with remote test administration and automated scoring. (PsycINFO
      Database Record

PMID- 27690505
TI  - Daily relations among affect, urge, targeted naltrexone, and alcohol use in young
      adults.
AB  - Heavy drinking among young adults is a serious public health problem. Naltrexone,
      an opioid antagonist, has been shown to reduce drinking in young adults compared
      to placebo and can be taken on a targeted (i.e., as needed) basis. Understanding
      risk factors for drinking and naltrexone effects within-person in young adults
      may help to optimize the use of targeted naltrexone. The current study was a
      secondary analysis of daily diary data from 127 (n = 40 female) young adults (age
      18-25) enrolled in a double-blind clinical trial of daily (25 mg) plus targeted
      (25 mg) naltrexone versus placebo. Hierarchical linear models were used to
      examine the effects of daily affect, urge, and taking targeted medication on same
      day risk of drinking to intoxication (defined as estimated blood-alcohol
      concentration, BAC >= .08 g%). Results indicated urge significantly mediated
      within-person positive affect-drinking relations on a daily level. Specifically,
      positive affect was associated with greater urge to drink, which in turn was
      associated with greater odds of BAC >= .08 g%. Furthermore, days of greater
      positive affect and urge were associated with taking a targeted dose of
      medication, which reduced the likelihood of intoxication by nearly 23% in the
      naltrexone group compared to placebo. Gender and family history of alcohol
      dependence were examined as moderators of these daily level effects. These
      results provide further evidence of naltrexone's ability to reduce alcohol
      consumption in young adults and identify potential within-person risk processes
      related to heavy drinking that could inform alcohol-related interventions for
      this population. (PsycINFO Database Record

PMID- 27690506
TI  - Initial feasibility and validity of a prospective memory training program in a
      substance use treatment population.
AB  - Individuals with substance use disorders have shown deficits in the ability to
      implement future intentions, called prospective memory. Deficits in prospective
      memory and working memory, a critical underlying component of prospective memory,
      likely contribute to substance use treatment failures. Thus, improvement of
      prospective memory and working memory in substance use patients is an innovative
      target for intervention. We sought to develop a feasible and valid prospective
      memory training program that incorporates working memory training and may serve
      as a useful adjunct to substance use disorder treatment. We administered a single
      session of the novel prospective memory and working memory training program to
      participants (n = 22; 13 men, 9 women) enrolled in outpatient substance use
      disorder treatment and correlated performance to existing measures of prospective
      memory and working memory. Generally accurate prospective memory performance in a
      single session suggests feasibility in a substance use treatment population.
      However, training difficulty should be increased to avoid ceiling effects across
      repeated sessions. Consistent with existing literature, we observed superior
      performance on event-based relative to time-based prospective memory tasks.
      Performance on the prospective memory and working memory training components
      correlated with validated assessments of prospective memory and working memory,
      respectively. Correlations between novel memory training program performance and
      established measures suggest that our training engages appropriate cognitive
      processes. Further, differential event- and time-based prospective memory task
      performance suggests internal validity of our training. These data support the
      development of this intervention as an adjunctive therapy for substance use
      disorders. (PsycINFO Database Record

PMID- 27690508
TI  - Emotion and decision-making under uncertainty: Physiological arousal predicts
      increased gambling during ambiguity but not risk.
AB  - Uncertainty, which is ubiquitous in decision-making, can be fractionated into
      known probabilities (risk) and unknown probabilities (ambiguity). Although
      research has illustrated that individuals more often avoid decisions associated
      with ambiguity compared to risk, it remains unclear why ambiguity is perceived as
      more aversive. Here we examine the role of arousal in shaping the representation
      of value and subsequent choice under risky and ambiguous decisions. To
      investigate the relationship between arousal and decisions of uncertainty, we
      measure skin conductance response-a quantifiable measure reflecting sympathetic
      nervous system arousal-during choices to gamble under risk and ambiguity. To
      quantify the discrete influences of risk and ambiguity sensitivity and the
      subjective value of each option under consideration, we model fluctuating
      uncertainty, as well as the amount of money that can be gained by taking the
      gamble. Results reveal that although arousal tracks the subjective value of a
      lottery regardless of uncertainty type, arousal differentially contributes to the
      computation of value-that is, choice-depending on whether the uncertainty is
      risky or ambiguous: Enhanced arousal adaptively decreases risk-taking only when
      the lottery is highly risky but increases risk-taking when the probability of
      winning is ambiguous (even after controlling for subjective value). Together,
      this suggests that the role of arousal during decisions of uncertainty is
      modulatory and highly dependent on the context in which the decision is framed.
      (PsycINFO Database Record

PMID- 27690509
TI  - Replicable effects of primes on human behavior.
AB  - [Correction Notice: An Erratum for this article was reported online in Journal of
      Experimental Psychology: General on Oct 31 2016 (see record 2016-52334-001). ]
      The effect of primes (i.e., incidental cues) on human behavior has become
      controversial. Early studies reported counterintuitive findings, suggesting that
      primes can shape a wide range of human behaviors. Recently, several studies
      failed to replicate some earlier priming results, raising doubts about the
      reliability of those effects. We present a within-subjects procedure for priming
      behavior, in which participants decide whether to bet or pass on each trial of a
      gambling game. We report 6 replications (N = 988) showing that primes
      consistently affected gambling decisions when the decision was uncertain.
      Decisions were influenced by primes presented visibly, with a warning to ignore
      the primes (Experiments 1 through 3) and with subliminally presented masked
      primes (Experiment 4). Using a process dissociation procedure, we found evidence
      that primes influenced responses through both automatic and controlled processes
      (Experiments 5 and 6). Results provide evidence that primes can reliably affect
      behavior, under at least some conditions, without intention. The findings suggest
      that the psychological question of whether behavior priming effects are real
      should be separated from methodological issues affecting how easily particular
      experimental designs will replicate.

PMID- 27690507
TI  - Prescription stimulant medication misuse: Where are we and where do we go from
      here?
AB  - Prescription stimulants, including methylphenidate (e.g., Ritalin) and
      amphetamine compounds (e.g., dextroamphetamine; Adderall), have been approved by
      the U.S. Food and Drug Administration for the treatment of attention
      deficit/hyperactivity disorder (ADHD) and are classified by the United States
      Drug Enforcement Administration as Schedule II medications because of their high
      potential for abuse and dependence (Drug Enforcement Administration, U.S.
      Department of Justice, 2015). Despite the potential health and judicial
      consequences, misuse of prescription stimulants, typically defined as taking
      stimulants without a valid prescription, or use of stimulants other than as
      prescribed, has become a serious problem in the United States and abroad,
      especially on college campuses. The purpose of the present article is to review
      historical information concerning prescription stimulants and to summarize the
      literature with respect to misuse among adults, particularly college students,
      including risk factors, mediators and moderators, and motivations for
      prescription stimulant misuse. In addition, evidence is presented concerning the
      question of whether prescription stimulants truly enhance cognitive functioning
      in individuals with and without ADHD, and the ethical and professional
      implications of these findings are explored. Lastly, recommendations for
      addressing prescription stimulant misuse and suggestions for future research are
      advanced. (PsycINFO Database Record

PMID- 27690510
TI  - An integrated perspective on insight.
AB  - The present study on insight is based on an integration of Kaplan and Simon's
      (1990) information processing theory of insight, a cognitive style theory, and
      achievement motivation theory. The style theory is the Assimilator (rule
      oriented, familiarity seeking)-Explorer (novelty seeking, explorative) styles
      (Kaufmann, 1979). Our hypothesis is that the effectiveness of 2 types of search
      constraints (prior experience and solution hints) for solving insight problems is
      moderated by both cognitive style and achievement needs, and depending on optimal
      levels of achievement motivation for different task conditions. We tested the
      hypothesis in a randomized experiment in which 3 levels of achievement needs and
      1 type of search constraint (solution hints were available or not available) were
      experimentally manipulated. In addition, participants completed a cognitive style
      test, a measure of prior problem-solving experience (the second type of search
      constraint), and controls for intelligence. There were 476 participants (the mean
      age was 18.4 years). Results revealed 2 similar and significant 3-way
      interactions between styles, achievement needs, and the 2 types of search
      constraints. The pattern of interaction supported the idea that stylistic
      competence for the task characteristics (with and without search constraints
      available), when combined with manipulated achievement needs, predicted
      performance in counterintuitive ways but in line with the classic achievement
      motivation theory. With appropriate stylistic competence for the task
      characteristics elevated achievement needs led to poorer performance. With less
      appropriate stylistic competence, performance improved with increasing
      motivation. Implications for information processing theory are discussed.
      (PsycINFO Database Record

PMID- 27690511
TI  - "A general benevolence dimension that links neural, psychological, economic, and
      life-span data on altruistic tendencies": Correction to Hubbard et al. (2016).
AB  - Reports an error in "A general benevolence dimension that links neural,
      psychological, economic, and life-span data on altruistic tendencies" by Jason
      Hubbard, William T. Harbaugh, Sanjay Srivastava, David Degras and Ulrich Mayr
      (Journal of Experimental Psychology: General, Advanced Online Publication, Aug
      11, 2016, np). In the article, there was an error in the Task, Stimuli, and
      Procedures section. In the 1st sentence in the 6th paragraph, "Following the
      scanning phase, participants completed self-report questionnaires meant to
      reflected the Prosocial Disposition construct: the agreeableness scale from the
      Big F, which includes empathic concern and perspective-taking, and a scale of
      personality descriptive adjectives related to altruistic behavior (Wood, Nye, &
      Saucier, 2010)." should have read: "Following the scanning phase, participants
      completed self-report questionnaires that contained scales to reflect the
      Prosocial Disposition construct: the Big Five Inventory (BFI; John et al., 1991),
      from which we used the agreeableness scale to measure prosocial disposition; the
      Interpersonal Reactivity Index (IRI; Davis, 1980), from which we used the
      empathic concern and perspective-taking scales; and a scale of personality
      descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier,
      2010)." (The following abstract of the original article appeared in record 2016
      39037-001.) Individual and life span differences in charitable giving are an
      important economic force, yet the underlying motives are not well understood. In
      an adult, life span sample, we assessed manifestations of prosocial tendencies
      across 3 different measurement domains: (a) psychological self-report measures,
      (b) actual giving choices, and (c) fMRI-derived, neural indicators of "pure
      altruism." The latter expressed individuals' activity in neural valuation areas
      when charities received money compared to when oneself received money and thus
      reflected an altruistic concern for others. Results based both on structural
      equation modeling and unit-weighted aggregate scores revealed a strong higher
      order General Benevolence dimension that accounted for variability across all
      measurement domains. The fact that the neural measures likely reflect pure
      altruistic tendencies indicates that General Benevolence is based on a genuine
      concern for others. Furthermore, General Benevolence exhibited a robust increase
      across the adult life span, potentially providing an explanation for why older
      adults typically contribute more to the public good than young adults.

PMID- 27690512
TI  - Distractibility is a function of engagement, not task difficulty: Evidence from a
      new oculomotor capture paradigm.
AB  - It has been shown that when humans require a brief moment of concentration or
      mental effort, they tend to avert their gaze away from the attended location (or
      even blink). Similarly, participants tend to miss unexpected events when they are
      highly focused on a task. We present an engagement theory of distractibility that
      is meant to capture the relationship between participants' engagement in a task
      and reduction in sensitivity to new sensory events in a broad range of
      situations. In a series of experiments, we asked participants to perform
      different cognitive tasks of varying degrees of difficulty while we measured
      spontaneous oculomotor capture by new images that were completely unrelated to
      the participants' task. The images appeared while participants were cognitively
      engaged in the task. Our results showed that increased cognitive engagement
      produced decreased sensitivity to visual events. We propose that individual
      differences in intrinsic motivation play a large role in determining sensitivity
      to task unrelated events. In addition, our results also indicate that changes in
      task difficulty on a trial-to-trial basis do not generate trial-by-trial
      differences in oculomotor capture. Importantly, we believe our framework provides
      us with a promising way of extending laboratory findings to many real world
      situations. (PsycINFO Database Record

PMID- 27690513
TI  - Long-term working memory and transient storage in reading comprehension: What is
      the evidence? Comment on Foroughi, Werner, Barragan, and Boehm-Davis (2015).
AB  - In a recent article, Foroughi, Werner, Barragan, and Boehm-Davis (2015)
      demonstrated that interspersing interruptions between paragraphs during reading
      sometimes reduces accuracy on comprehension questions. We propose an account of
      their findings within long-term working memory (LTWM) theory. Our account
      proposes that interruptions interfere with the accessibility of the generated
      encodings of the text in long-term memory (LTM) and that unimpaired continued
      comprehension requires restoration of access to these memory encodings during the
      resumption of reading after the interruptions. It is consistent with the accuracy
      of question answering being substantially preserved in their study, which is
      seemingly inconsistent with their transient storage account. This theoretical
      controversy does not diminish the importance of Foroughi et al.'s results: We
      agree that additional research is needed to understand when and how interruptions
      impact various aspects of comprehension. (PsycINFO Database Record

PMID- 27690514
TI  - Multiple interpretations of long-term working memory theory: Reply to Delaney and
      Ericsson (2016).
AB  - This reply is in response to Delaney and Ericsson (2016), who argue that the
      results of our recent research (Foroughi, Werner, Barragan, & Boehm-Davis, 2015)
      can be explained by Ericsson and Kintsch's (1995) long-term working memory (LTWM)
      theory. Our original work was designed to test the prediction made by LTWM theory
      that interruptions of up to 30 s in duration would not disrupt reading
      performance. We conducted the work following the method and outcome measures
      recommended by Ericsson and Kintsch (1995). Our data were clear: interruptions
      disrupted reading comprehension. We believe that these data do not support
      predictions made by LTWM theory. Although we appreciate Delaney and Ericsson's
      (2016) comments, we are unsure how best to move forward because it appears that
      some of their comments are not consistent with the published work on LTWM theory.
      Because of the inconsistent and contradictory claims surrounding LTWM theory, the
      theory does not appear to be falsifiable, or is in danger of becoming
      unfalsifiable. Creating and testing theory is vital for the advancement of
      psychological science, but it appears that testing predictions made by LTWM would
      be very difficult, if not impossible, given the fluid state of the theory.
      (PsycINFO Database Record

PMID- 27690515
TI  - The roles of perceptual and conceptual information in face recognition.
AB  - The representation of familiar objects is comprised of perceptual information
      about their visual properties as well as the conceptual knowledge that we have
      about them. What is the relative contribution of perceptual and conceptual
      information to object recognition? Here, we examined this question by designing a
      face familiarization protocol during which participants were either exposed to
      rich perceptual information (viewing each face in different angles and
      illuminations) or with conceptual information (associating each face with a
      different name). Both conditions were compared with single-view faces presented
      with no labels. Recognition was tested on new images of the same identities to
      assess whether learning generated a view-invariant representation. Results showed
      better recognition of novel images of the learned identities following
      association of a face with a name label, but no enhancement following exposure to
      multiple face views. Whereas these findings may be consistent with the role of
      category learning in object recognition, face recognition was better for labeled
      faces only when faces were associated with person-related labels (name,
      occupation), but not with person-unrelated labels (object names or symbols).
      These findings suggest that association of meaningful conceptual information with
      an image shifts its representation from an image-based percept to a view
      invariant concept. They further indicate that the role of conceptual information
      should be considered to account for the superior recognition that we have for
      familiar faces and objects. (PsycINFO Database Record

PMID- 27690516
TI  - Off the rails in rural South Carolina: a qualitative study of healthcare provider
      perspectives on the long-term health impact of the Graniteville train disaster.
AB  - INTRODUCTION: In 2005, a train derailment and subsequent chlorine spill ravaged
      the rural town of Graniteville in South Carolina, resulting in one of the worst
      chlorine gas exposures in US. HISTORY: Significant health and economic challenges
      persist in the community more than a decade later. Healthcare providers offered
      healthcare services to community members in the immediate aftermath of the
      disaster, and many still live in the community and continue to provide healthcare
      services. As such, healthcare professionals provide a unique and important
      perspective to help understand the impact of the disaster on the community's
      health. The purpose of this study was to explore healthcare providers'
      perspectives about the long-term effects of the disaster on community health,
      healthcare access, and wellbeing. METHODS: Semi-structured interviews were
      conducted with 30 healthcare providers who treated survivors of the Graniteville
      train disaster. A qualitative, essentialist, inductive thematic analytic approach
      was used to analyze study data. RESULTS: Four themes emerged regarding the
      disaster's long-term impact: effects of chlorine exposure on physical health,
      issues with healthcare access, residual effects of the disaster on personal and
      community wellbeing, and improving health and community wellbeing. CONCLUSIONS:
      Disaster recovery should not be considered solely an acute event; agencies must
      be prepared for long-term, potentially chronic ailments, particularly in
      underserved, rural communities. Efforts to address the long-term health needs of
      communities post-disaster should consider the perspectives of healthcare
      providers to offer a well-rounded assessment of community needs. Study findings
      can help inform future disaster response strategies in communities locally and
      globally.

PMID- 27690518
TI  - You Seldom Get a Second Chance With a Gunshot: Lethality of Suicidal Acts.

PMID- 27690517
TI  - The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder.
AB  - OBJECTIVE: The authors sought to determine the risk of treatment-emergent mania
      associated with methylphenidate, used in monotherapy or with a concomitant mood
      stabilizing medication, in patients with bipolar disorder. METHOD: Using linked
      Swedish national registries, the authors identified 2,307 adults with bipolar
      disorder who initiated therapy with methylphenidate between 2006 and 2014. The
      cohort was divided into two groups: those with and those without concomitant mood
      stabilizing treatment. To adjust for individual-specific confounders, including
      disorder severity, genetic makeup, and early environmental factors, Cox
      regression analyses were used, conditioning on individual to compare the rate of
      mania (defined as hospitalization for mania or a new dispensation of stabilizing
      medication) 0-3 months and 3-6 months after medication start following nontreated
      periods. RESULTS: Patients on methylphenidate monotherapy displayed an increased
      rate of manic episodes within 3 months of medication initiation (hazard
      ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By
      contrast, for patients taking mood stabilizers, the risk of mania was lower after
      starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results
      were observed when only hospitalizations for mania were counted. CONCLUSIONS: No
      evidence was found for a positive association between methylphenidate and
      treatment-emergent mania among patients with bipolar disorder who were
      concomitantly receiving a mood-stabilizing medication. This is clinically
      important given that up to 20% of people with bipolar disorder suffer from
      comorbid ADHD. Given the markedly increased hazard ratio of mania following
      methylphenidate initiation in bipolar patients not taking mood stabilizers,
      careful assessment to rule out bipolar disorder is indicated before initiating
      monotherapy with psychostimulants.

PMID- 27690519
TI  - Broad- versus Narrow-Spectrum Oral Antibiotic Transition and Outcomes in Health
      Care-associated Pneumonia.
AB  - RATIONALE: Guidelines recommend a switch from intravenous to oral antibiotics
      once patients who are hospitalized with pneumonia achieve clinical stability.
      However, little evidence guides the selection of an oral antibiotic for patients
      with health care-associated pneumonia, especially where no microbiological
      diagnosis is made. OBJECTIVES: To compare outcomes between patients who were
      transitioned to broad- versus narrow-spectrum oral antibiotics after initially
      receiving broad-spectrum intravenous antibiotic coverage. METHODS: We performed a
      secondary analysis of an existing database of adults with community-onset
      pneumonia admitted to seven Utah hospitals. We identified 220 inpatients with
      microbiology-negative health care-associated pneumonia from 2010 to 2012. After
      excluding inpatient deaths and treatment failures, 173 patients remained in which
      broad-spectrum intravenous antibiotics were transitioned to an oral regimen. We
      classified oral regimens as broad-spectrum (fluoroquinolone) versus narrow
      spectrum (usually a beta-lactam). We compared demographic and clinical
      characteristics between groups. Using a multivariable regression model, we
      adjusted outcomes by severity (electronically calculated CURB-65), comorbidity
      (Charlson Index), time to clinical stability, and length of intravenous therapy.
      MEASUREMENTS AND MAIN RESULTS: Age, severity, comorbidity, length of intravenous
      therapy, and clinical response were similar between the two groups. Observed 30
      day readmission (11.9 vs. 21.4%; P = 0.26) and 30-day all-cause mortality (2.3
      vs. 5.3%; P = 0.68) were also similar between the narrow and broad oral
      antibiotic groups. In multivariable analysis, we found no statistically
      significant differences for adjusted odds of 30-day readmission (adjusted odds
      ratio, 0.56; 95% confidence interval, 0.06-5.2; P = 0.61) or 30-day all-cause
      mortality (adjusted odds ratio, 0.55; 95% confidence interval, 0.19-1.6; P =
      0.26) between narrow and broad oral antibiotic groups. CONCLUSIONS: On the basis
      of analysis of a limited number of patients observed retrospectively, our
      findings suggest that it may be safe to switch from broad-spectrum intravenous
      antibiotic coverage to a narrow-spectrum oral antibiotic once clinical stability
      is achieved for hospitalized patients with health care-associated pneumonia when
      no microbiological diagnosis is made. A larger retrospective study with
      propensity matching or regression-adjusted test of equivalence or ideally a
      prospective comparative effectiveness study will be necessary to confirm our
      observations.

PMID- 27690522
TI  - A Message From the Editor.

PMID- 27690520
TI  - Introduction.

PMID- 27690524
TI  - Introduction.

PMID- 27690526
TI  - Stephen Morris: Scientist, Editor, Educator, Scholar (1956-2009).

PMID- 27690525
TI  - Anticoagulation Practices during Venovenous Extracorporeal Membrane Oxygenation
      for Respiratory Failure. A Systematic Review.
AB  - BACKGROUND: The optimal anticoagulation strategy for venovenous extracorporeal
      membrane oxygenation (VV-ECMO) is not known. OBJECTIVES: To evaluate the safety
      of anticoagulation strategies and monitoring during VV-ECMO for respiratory
      failure. DATA SOURCES: We conducted a systematic review to evaluate the
      association between anticoagulation strategies during VV-ECMO and prespecified
      outcomes, including major bleeding episodes, thrombotic events, and in-hospital
      mortality. We included articles published between 1977 and January 30, 2015.
      Study quality was assessed using the Newcastle-Ottawa scoring system. A separate
      meta-analysis was not planned. DATA EXTRACTION: Data were independently extracted
      by two authors and collected on a standardized report form. SYNTHESIS: A total of
      18 studies (n = 646) were included; 17 studies enrolled patients with acute
      respiratory distress syndrome. Across all studies, the duration of VV-ECMO
      support ranged from 4 to 20 days. Patients received an average of 2.3 (+/-3.9)
      units of transfused red blood cells per day. The bleeding rate across all studies
      was 16%, and the rate of thrombosis was 53%. Among seven studies (199 patients)
      targeting a specified activated partial thromboplastin time (aPTT), there were 37
      (19%) major bleeding episodes and 53 (27%) major thromboses. Among five studies
      (43 patients) with aPTT targets of 60 seconds or greater, there were 24 (56%)
      bleeding episodes and 3 (7%) clotting events. Three studies (156 patients) with
      an aPTT target under 60 seconds reported 13 (8%) and 50 (32%) significant
      bleeding and thrombotic events, respectively. The most commonly reported
      thrombotic events were circuit-related clotting and deep-vein thrombosis.
      Mortality during VV-ECMO varied across the studies, ranging from 0 to at least
      50% at heterogeneous time points. The total number of deaths for all studies
      combined was 186 (29%). CONCLUSIONS: The role and optimal therapeutic targets for
      anticoagulation during VV-ECMO are unclear. Previously published studies are
      limited by retrospective, observational design, small cohorts, and patient
      heterogeneity. The clinical significance of reported thrombotic complications is
      largely unknown. This systematic review underscores the need for randomized
      controlled trials of anticoagulation strategies for patients undergoing VV-ECMO
      for respiratory failure.

PMID- 27690528
TI  - Intrinsic Foot Muscle Activation During Specific Exercises: A T2 Time Magnetic
      Resonance Imaging Study.
AB  - CONTEXT: The intrinsic foot muscles maintain the medial longitudinal arch and aid
      in force distribution and postural control during gait. Impaired intrinsic foot
      muscle function has been linked to various foot conditions. Several
      rehabilitative exercises have been proposed to improve it; however, literature
      that identifies which individual muscles are activated during specific intrinsic
      foot-muscle exercises is lacking. OBJECTIVE: To describe changes in activation of
      the intrinsic plantar foot muscles after 4 exercises as measured with T2 magnetic
      resonance imaging (MRI). DESIGN: Descriptive laboratory study. SETTING: Research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Eight healthy National Collegiate
      Athletic Association Division I collegiate cross-country and track athletes (5
      men and 3 women: age = 20 +/- 0.93 years, height = 180.98 +/- 10.84 cm, mass =
      70.91 +/- 7.82 kg). INTERVENTION(S): Participants underwent T2 MRI before and
      after each exercise. They completed 1 set of 40 repetitions of each exercise
      (short-foot exercise, toes spread out, first-toe extension, second- to fifth-toes
      extension). MAIN OUTCOME MEASURE(S): Percentage increases in muscle activation of
      the abductor hallucis, flexor digitorum brevis, abductor digiti minimi, quadratus
      plantae, flexor digiti minimi, adductor hallucis oblique, flexor hallucis brevis,
      and interossei and lumbricals (analyzed together) after each exercise were
      assessed using T2 MRI. RESULTS: All muscles showed increased activation after all
      exercises. The mean percentage increase in activation ranged from 16.7% to 34.9%
      for the short-foot exercise, 17.3% to 35.2% for toes spread out, 13.1% to 18.1%
      for first-toe extension, and 8.9% to 22.5% for second- to fifth-toes extension.
      All increases in activation had associated 95% confidence intervals that did not
      cross zero. CONCLUSIONS: Each of the 4 exercises was associated with increased
      activation in all of the plantar intrinsic foot muscles evaluated. These results
      may have clinical implications for the prescription of specific exercises to
      target individual intrinsic foot muscles.

PMID- 27690530
TI  - Introduction.

PMID- 27690531
TI  - Premature Ovarian Insufficiency: New Perspectives on Genetic Cause and Phenotypic
      Spectrum.
AB  - Premature ovarian insufficiency (POI) is one form of female infertility, defined
      by loss of ovarian activity before the age of 40 and characterized by amenorrhea
      (primary or secondary) with raised gonadotropins and low estradiol. POI affects
      up to one in 100 females, including one in 1000 before the age of 30. Substantial
      evidence suggests a genetic basis for POI; however, the majority of cases remain
      unexplained, indicating that genes likely to be associated with this condition
      are yet to be discovered. This review discusses the current knowledge of the
      genetic basis of POI. We highlight genes typically known to cause syndromic POI
      that can be responsible for isolated POI. The role of mouse models in
      understanding POI pathogenesis is discussed, and a thorough list of candidate POI
      genes is provided. Identifying a genetic basis for POI has multiple advantages,
      such as enabling the identification of presymptomatic family members who can be
      offered counseling and cryopreservation of eggs before depletion, enabling
      personalized treatment based on the cause of an individual's condition, and
      providing better understanding of disease mechanisms that ultimately aid the
      development of improved treatments.

PMID- 27690529
TI  - Association of Physical Inactivity, Weight, Smoking, and Prior Injury on Physical
      Performance in a Military Setting.
AB  - CONTEXT:  Although inactivity, being overweight, smoking, and a history of injury
      are identified as risk factors for poor health and injury, few authors have
      examined their association on physical performance. Young adults may be more
      likely to adopt healthier lifestyles if they understand the effect of health
      behaviors on performance. OBJECTIVE:  To determine the association of being
      overweight, smoking, inactivity, and a history of injury with physical
      performance. DESIGN:  Cross-sectional study. SETTING:  Military population.
      PATIENTS OR OTHER PARTICIPANTS:  Active-duty service members (N = 1466; 1380 men,
      86 women; age = 24.7 +/- 5.0 years; body mass index = 26.7 +/- 3.4 kg/m2). MAIN
      OUTCOME MEASURE(S):  Participants performed 8 measures (the triple-crossover hop
      for distance, the 6-m timed-hop test, the Functional Movement Screen, the Lower
      Quarter Y-Balance Test, the Upper Quarter Y-Balance Test, and the 3-event Army
      Physical Fitness Test) for evaluation of endurance, strength, muscular endurance,
      power, agility, balance, and motor control. Participants were categorized based
      on the number of health risk factors present. Using an analysis of covariance, we
      assessed the relationship between risk factors and physical performance with age
      and sex as covariates. RESULTS:  Compared with those who had no risk factors
      (27.9% of men, 34.9% of women), physical performance was worse in those who had
      1, 2, or 3 to 4 risk factors present by 4.3%, 6.7%, and 10.3%, respectively.
      Decrements in performance for those with 3 to 4 risk factors ranged from 3.3% to
      14.4%. CONCLUSIONS:  An unhealthy lifestyle habit or a history of injury was
      negatively associated with physical performance. Physical performance decrements
      were associated with the number of risk factors present. Understanding how risk
      factors contribute to decreased physical performance may enable clinicians to
      improve compliance with injury-prevention programs in occupational settings in
      which a young and relatively healthy workforce may be more concerned about
      performance than health.

PMID- 27690532
TI  - Correction for Volume 216, Table 1, p. 26, in the article titled "Mass culture
      and characterization of tumor cells from a naturally occurring invertebrate
      cancer model: applications for human and animal disease and environmental
      health." Biol. Bull. 216(1): 23-39.

PMID- 27690533
TI  - A Special Role for Marine Biology.

PMID- 27690536
TI  - Record keeping in radiology: are we doing enough?
AB  - In modern medical practice, there is an ever-increasing rise in litigation. A
      strong emphasis is placed on good record keeping as an integral part of patient
      care and the clinician legal defence. This commentary describes the potential
      flaws and vulnerabilities in the radiologist record keeping and the potential
      implications for patient care.

PMID- 27690538
TI  - Role of diffusion weighted magnetic resonance imaging in a rat model of
      testicular torsion.
AB  - OBJECTIVE: The purpose of this study was to investigate the usefulness of
      diffusion-weighted imaging (DWI) in the detection of different degrees of
      testicular torsion (TT) at the 8th hour and testicular salvageability at the 24th
      hour of torsion. METHODS: 31 rats were randomly classified into 4 groups. In
      Group 1 (sham-control group), the left testicle was kept outside and replaced.
      Left testicles were kept outside and twisted 360 degrees  in Group 2, 720 degrees
      in Group 3 and 1080 degrees  in Group 4. Later, DWI was performed at 8th and
      24th hours. After DWI, bilateral radical orchiectomy and histopathological
      examination were performed. Apparent diffusion coefficient (ADC) maps were
      obtained with b-factors of 0 and 800 s mm-2. Comparisons of ADC values and damage
      in testicles were performed with Kruskal-Wallis test. RESULTS: Sensitivity of DWI
      in the diagnosis of TT was 12.5% for 360 degrees  torsion, 100% for 720 degrees 
      torsion and 1080 degrees  torsion at the 8th hour of torsion. Mean ADC values of
      the left testicles increased significantly at the 24th hour of torsion in Groups
      3 and 4. All testicles in Groups 3 and 4 were observed to be irrecoverable on
      histopathological examination. CONCLUSION: Increased ADC values in the affected
      testicle may represent irreversible tissue damage. So, immediate surgery is not
      required at this stage, which may reduce morbidity and mortality caused by
      immediate surgery and anaesthesia. Advances in knowledge: TT can be diagnosed
      easily by DWI without administrating any contrast material. DWI findings in the
      affected testicle may represent testicular salvageability.

PMID- 27690540
TI  - Theodore Holmes Bullock (1915-2005).

PMID- 27690539
TI  - Intimate relationship quality, self-concept and illness acceptance in those with
      multiple sclerosis.
AB  - Lower levels of Intimate Relationship Quality (IRQ) have been found in those with
      Multiple Sclerosis (MS) compared to the general population. This study examined
      an MS sample to see whether IRQ was positively associated with self-concept,
      whether IRQ was positively associated with MS illness acceptance and whether IRQ
      was predicted by self-concept and illness acceptance. In this cross-sectional
      study, 115 participants with MS who were in an intimate relationship completed an
      online survey advertised on MS related websites. The survey assessed demographic
      variables, MS illness variables and levels of IRQ, self-concept and illness
      acceptance. Results revealed that IRQ was significantly positively associated
      with self-concept and with illness acceptance. Multiple hierarchical linear
      regression analysis revealed that, after controlling for illness duration and
      level of disability, self-concept significantly predicted IRQ but illness
      acceptance did not significantly predict IRQ. This study addressed several gaps
      and methodological flaws in the literature and was the first known to assess
      predictors of IRQ in those with MS. The results suggest that self-concept could
      be a potential target for individual and couple psychological interventions to
      improve IRQ and contribute to improved outcomes for those with MS.

PMID- 27690541
TI  - Dart Symposium on Learning and Memory.

PMID- 27690542
TI  - Biological Bulletin Virtual Symposium: Marine Invertebrate Models of Learning and
      Memory.

PMID- 27690543
TI  - Causes of variation in the neutrophil-lymphocyte and platelet-lymphocyte ratios:
      a twin-family study.
AB  - AIM: Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are
      biomarkers for disease development, for whom little is known about causes of
      variation in the general population. MATERIALS & METHODS: We estimated the
      heritability of PLR and NLR and examined their association with gender,
      demographic, lifestyle and environmental factors in a Dutch nonpatient twin
      family population (n = 8108). RESULTS: Heritability was estimated at 64% for PLR
      and 36% for NLR. Men had on average higher NLR, but lower PLR levels than women.
      PLR and NLR increased significantly with age, decreased in colder months and
      showed small but significant sex- and age-specific associations with body
      composition and smoking. CONCLUSION: NLR and PLR levels are heritable and
      influenced by age, sex and environmental factors, such as seasonal conditions and
      lifestyle.

PMID- 27690545
TI  - Lynn Margulis (1938-2011) Truth Straight On: Reflections on the Vision and Spirit
      of Lynn Margulis.

PMID- 27690544
TI  - Prevalence and psychosocial correlates of suicidal ideation among pregnant women
      living with HIV in Mpumalanga Province, South Africa.
AB  - Pregnant women living with HIV (WLHIV) in South Africa (SA) report higher rates
      of suicidal ideation than those who are HIV uninfected, and antenatal suicidal
      ideation has been previously associated with adverse maternal and neonatal
      outcomes. Few studies have attempted to identify correlates and psychosocial
      predictors of suicidal ideation in this population. In this study, we sought to
      estimate the prevalence of and identify risk factors for suicidal ideation among
      pregnant WLHIV in rural SA (N = 673). Thirty-nine percent of women endorsed
      suicidal ideation (95% CI: 35.2% to 42.3%) and in multivariable logistic
      regression analysis, suicidal ideation was associated with intimate partner
      violence and stigma, which interacted to multiplicatively increase the odds of
      suicidal thoughts. Given the high rates of reported suicidal ideation identified
      in this sample, and the potential harm to mothers and neonates, suicide risk
      assessment and management protocols for pregnant WLHIV should be considered for
      inclusion in the standard of care in rural SA.

PMID- 27690546
TI  - Compassion in the Eye of the Beholder.

PMID- 27690547
TI  - Edward Cowles (1837-1919).

PMID- 27690548
TI  - Early Detection of Psychosis Vulnerability: Progress, Opportunity, and Caution.

PMID- 27690550
TI  - CORRECTION.

PMID- 27690549
TI  - Effects of Ultra-Low-Dose Buprenorphine on Suicidal Ideation Confounded by
      Physical Pain Relief?

PMID- 27690551
TI  - Treatment Controversies in Adult ADHD.

PMID- 27690552
TI  - Children of Depressed Parents: The Long View.

PMID- 27690553
TI  - Ultra-Low-Dose Buprenorphine for Mental Pain: Response to Ruan et al.

PMID- 27690555
TI  - Detrimental Side Effects of Repeated Ketamine Infusions in the Brain.

PMID- 27690556
TI  - Putting Psychosis in Its Place.

PMID- 27690557
TI  - Sustaining the Long-Term Effects of Supported Employment for Persons With
      Psychiatric Disabilities.

PMID- 27690559
TI  - APA Council Reports.
AB  - At the fall component meetings of the American Psychiatric Association in Crystal
      City, Va., September 14-17, 2016, the APA councils heard reports from their
      components. Following are summaries of the activities of the councils and their
      components.

PMID- 27690560
TI  - Antidepressant Efficacy and Dosing Comparisons of Ketamine Enantiomers: Response
      to Hashimoto.

PMID- 27690561
TI  - Down-Regulation of SIRT1 Gene Expression in Major Depressive Disorder.

PMID- 27690564
TI  - Empirical modeling of metabolic alkalosis induced by sodium bicarbonate
      ingestion.
AB  - Biphasic responses of blood HCO3- concentration and H+ concentration following
      ingestion of 3 doses of NaHCO3 (0.1, 0.2, 0.3 g.kg-1) were assessed in 8 men. For
      HCO3- concentration, there were significant effects of dose on maximum responses
      and timing, as well amplitudes, onsets, and/or time constants of phases 1 and 2.
      Fewer significant effects of dose were observed for H+ concentration and
      additional data demonstrated differential effects of dose on HCO3- concentration
      and H+ concentration responses and underlying phases.

PMID- 27690562
TI  - Transactional sex among men who have sex with men in the French Antilles and
      French Guiana: frequency and associated factors.
AB  - The French Antilles (Martinique, Saint Martin and Guadeloupe) and French Guiana
      are the French territories most affected by the HIV epidemic. Some population
      groups such as men who have sex with men (MSM), especially those involved in
      transactional sex, are thought to be particularly vulnerable to HIV but few data
      exist to help characterize their health-related needs and thus implement relevant
      prevention interventions. To fill this knowledge gap, we used data collected from
      an HIV/AIDS Knowledge, Attitudes, Behaviours and Practices survey conducted in
      2012 among MSM living in the French Antilles and French Guiana and recruited
      through snowball sampling. Our objectives were to compare social and demographic
      characteristics and sexual behaviours between MSM engaging in transactional sex
      and MSM not engaging in transactional sex and to identify factors associated with
      transactional sex involvement using a logistic regression model. A total of 733
      MSM were interviewed, 21% of whom reported to undergo transactional sex. Their
      behaviour and social and demographic characteristics were different from other
      MSMs' and they were more exposed to factors that are recognized to potentiate HIV
      vulnerability, at the individual, community, network and structural levels. The
      variables positively associated with sex trade involvement were having ever
      consumed drug (OR = 2.84 [1.23-6.52]; p = .002), having a greater number of sex
      partners than the median (OR = 8.31 [4.84-14.30]; p < .001), having experienced
      intimate partner violence (OR = 1.72 [0.99-3.00]; p = .053) and having undergone
      physical aggression because of sexual orientation (OR = 2.84 [1.23-6.52]; p =
      .014). Variables negatively associated with sex trade involvement were being
      older (OR = 0.93 [0.90-0.97] per year; p = .001), having a stable administrative
      situation (OR = 0.10 [0.06-0.19]; p < .001), having a stable housing (OR = 0.29
      [0.15-0.55]; p < .001) and being employed full-time (OR = 0.29 [1.23-6.52]; p =
      .002).

PMID- 27690565
TI  - Proton-pump inhibitor therapy and vitamin B12 status in an inpatient hospital
      setting.
AB  - The risk for impaired vitamin B12 status increases with age, as does the use of
      proton pump inhibitors (PPI). Long-term use of PPIs is associated with several
      nutritional deficiencies including B12. Currently, there are no recommendations
      for B12 screening among patients taking PPIs. Data were abstracted on B12
      concentrations, B12-containing supplement use, medications, and select
      hematological values from a retrospective chart review of 658 adults, 391 with
      serum B12 concentrations, admitted to 6 different medical units at 2 regional
      hospitals in Southwestern Ontario between 2010 and 2012. We found no difference
      between PPI users and nonusers and serum B12 concentrations (404 +/- 224 vs 369
      +/- 213 pmol/L; P = 0.0690). This may be due to use of B12 containing
      multivitamins in 41% of PPI users. Regression modelling found that aging
      increases the odds of having an impaired B12 status (<220 pmol/L) by 1.4 times
      and those using B12 supplements are almost 4 times more likely to have an
      impaired status. Mean corpuscular volume was not related to B12 status. In this
      population, older PPI users are more likely to be using multivitamins, which may
      delay nutritional deficiencies. However, the lower B12 concentrations of PPI
      users taking only B12 supplements is a concern and requires further research.
      Finally, physicians need to be aware that mean corpuscular volume is no longer
      recommended as an effective biomarker for B12 screening and updated screening
      protocols need to be used to reduce the possibility of adverse neurological
      effects from impaired B12 status.

PMID- 27690566
TI  - The effects of muscle action, repetition duration, and loading strategies of a
      whole-body, progressive resistance training programme on muscular performance and
      body composition in trained males and females.
AB  - Research has produced equivocal results with regard to eccentric (ECC) only
      compared with traditional concentric/eccentric resistance training (RT). When
      considered in relation to load- and repetition duration-accentuated (ECC)
      training as well as the use of isokinetic and isoinertial training methods, there
      is a relative dearth of literature considering multi-joint, multi-exercise RT
      interventions. The present study considered 59 male and female participants
      randomly divided in to 3 sex counterbalanced groups; ECC only (ECC, n = 20),
      repetition duration-accentuated ECC (ECC-A, n = 20), and traditional (CON, n =
      19) performing full-body, effort matched RT programmes for 2 days.week-1 for 10
      weeks. Outcomes were muscular performance, including absolute muscular endurance
      and predicted 1-repetition maximum, in addition to body composition. No
      significant between-groups differences were identified for change in muscular
      performance measures for leg press or chest press exercises, or for body
      composition changes. Analyses revealed a significantly greater improvement for
      CON compared with ECC groups (p < 0.05) for change in absolute muscular endurance
      for the pull-down exercise. Effect sizes for muscular performance changes were
      moderate to large for all groups and exercises (0.75-2.00). The present study
      supports previous research that ECC-only training produces similar improvements
      in muscular performance to traditional training where intensity of effort is
      controlled. Data herein further supports the use of uncomplicated, low-volume RT
      to momentary failure as an efficacious method of improving muscular performance
      in trained persons.

PMID- 27690567
TI  - The influence of subcutaneous fat on the relationship between body composition
      and ultrasound-derived muscle quality.
AB  - Ultrasound echo intensity (EI) values are a popular assessment of muscle quality.
      The relationship between EI and total (%fat) and regional (%fatlimb) body
      composition was examined in 40 men, prior to and after accounting for
      subcutaneous fat thickness. Uncorrected EI values suggest that muscle quality
      improves (r = -0.329 to -0.224; P = 0.038-0.165) with greater %fat and %fatlimb.
      However, corrected EI values indicated that muscle quality decreases (r = 0.711
      to 0.798; P < 0.001) with greater %fat and %fatlimb.

PMID- 27690568
TI  - A single session of exhaustive exercise markedly decreases circulating levels of
      guanidinoacetic acid in healthy men and women.
AB  - We evaluated the effects of exercise on circulating concentrations of
      guanidinoacetic acid (GAA) and creatine in 23 healthy volunteers subjected to
      running to exhaustion and free-weight bench-press to volitional failure. Blood
      was taken before and following each exercise session. Running induced a
      significant decrease in serum GAA by 20.1% (P < 0.001), while free-weight
      exercise reduced GAA by 11.7% (P < 0.001), suggesting the possible use of serum
      GAA as a novel biomarker of exhaustion.

PMID- 27690569
TI  - Short-term green tea extract supplementation attenuates the postprandial blood
      glucose and insulin response following exercise in overweight men.
AB  - Green tea extract (GTE) ingestion improves glucose homeostasis in healthy and
      diabetic humans, but the interactive effect of GTE and exercise is unknown. The
      present study examined the effect of short-term GTE supplementation on the
      glycemic response to an oral glucose load at rest and following an acute bout of
      exercise, as well as substrate oxidation during exercise. Eleven sedentary,
      overweight men with fasting plasma glucose (FPG) >=5.6 mmol.L-1 (age, 34 +/- 13
      years; body mass index = 32 +/- 5 kg.m-2; FPG = 6.8 +/- 1.0; mean +/- SD)
      ingested GTE (3* per day, 1050 mg.day-1 total) or placebo (PLA) for 7 days in a
      double-blind, crossover design. The effects of a 75-g glucose drink were assessed
      on 4 occasions during both GTE and PLA treatments: On days 1 and 5 at rest, and
      again following an acute bout of exercise on days 3 and 8. The glycemic response
      was assessed via an indwelling continuous glucose monitor (CGM) and venous blood
      draws. At rest, 1-h CGM glucose area under the curve was not different (P >
      0.05), but the postexercise response was lower after GTE versus PLA (330 +/- 53
      and 393 +/- 65 mmol.L-1.min-1, main effect of treatment, P < 0.05). The 1-h
      postprandial peaks in venous blood glucose (8.6 +/- 1.6 and 9.8 +/- 2.2 mmol.L-1)
      and insulin (96 +/- 59 and 124 +/- 68 MUIU.ml-1) were also lower postexercise
      with GTE versus PLA (time * treatment interactions, P < 0.05). In conclusion,
      short-term GTE supplementation did not affect postprandial glucose at rest;
      however, GTE was associated with an attenuated glycemic response following a
      postexercise oral glucose load. These data suggest that GTE might alter skeletal
      muscle glucose uptake in humans.

PMID- 27690570
TI  - Memory Enhancement by Bryostatin in Hermissenda.

PMID- 27690571
TI  - Blood Clotting in Limulus Immunity: Physiological Impairment of Clot-Entrapped
      Bacteria.

PMID- 27690572
TI  - Zinc Transport in Vertebrate Retina.

PMID- 27690573
TI  - Characterization of Anastral, Bipolar Spindle Development and Atypical
      Cytokinesis in Ammonia-Activated Sea Urchin Eggs.

PMID- 27690574
TI  - Sperm Load Impact on Female Courtship Behavior in the American Lobster (Homarus
      americanus).

PMID- 27690575
TI  - Visual Background Features That Elicit Mottled Body Patterns in Cuttlefish, Sepia
      officinalis.

PMID- 27690576
TI  - Anterograde Transport of Peptide-Conjugated Fluorescent Beads in the Squid Giant
      Axon Identifies a Zip-Code for the Synapse.

PMID- 27690577
TI  - Membrane Properties of Two Subtypes of Skate Bipolar Cells.

PMID- 27690578
TI  - Circadian Rhythms in the Locomotor Activity of Juvenile Horseshoe Crabs.

PMID- 27690579
TI  - The Second Transmembrane Domain 7' Position Influences Channel Kinetics in the
      Glycine alpha1 Receptor.

PMID- 27690580
TI  - The MBL Awards for 2004.
AB  - MBL Awards are given for the best paper presented at the General Scientific
      Meetings by a senior investigator, a junior investigator, a graduate student, and
      an undergraduate; additional papers are selected for Honorable Mention. The five
      presentations selected for MBL Awards this year reflect the broad scope of
      science at the Laboratory. Among these reports we find that lipopolysaccharide,
      the prime cause of gram-negative bacterial toxicity, occurs in eukaryotes; that a
      long-term decrease in synaptic strength is induced by a transient suppression of
      NMDA receptor activity; that cis editing in a trypanosome is a model of guide-RNA
      structure and function; that a female lobster's sperm load affects her choice of
      a mate; and that enzyme activities can be used to assess the stimulatory effect
      of increased estuarine nitrogen on the growth of sea lettuce. This year's
      awardees are listed below with the title of their presentation and the page on
      which their abstract appears. -The Editor August 2004.

PMID- 27690581
TI  - Genes Differentially Expressed in Growth Hormone Transgenic Salmon.

PMID- 27690582
TI  - Circadian Clock: Where Is It Located in the Limulus Brain?

PMID- 27690583
TI  - Local Synthesis of Presynaptic RNA in Squid Optic Lobe Slices.

PMID- 27690585
TI  - Diagnosis of Edwardsiella tarda Infection in Oyster Toadfish (Opsanus tau) Held
      at the Marine Resources Center.

PMID- 27690584
TI  - Circadian Rhythms in Limulus Visual Sensitivity Compensate for Day-Night Changes
      in Light Intensity.

PMID- 27690586
TI  - Abstracts from the 2004 General Scientific Meetings of the Marine Biological
      Laboratory.

PMID- 27690587
TI  - Transient NMDA Receptor Suppression Induces Long-Lasting Synaptic Depression.

PMID- 27690588
TI  - Life History Analysis of the Juvenile Horseshoe Crab in Pleasant Bay, Cape Cod.

PMID- 27690589
TI  - Isolation of the Myosin-V/Kinesin Heteromotor Complex by Sucrose Gradient
      Fractionation.

PMID- 27690590
TI  - Use of the Split-Ubiquitin Two-Hybrid System to Identify Proteins Interacting
      With the Alzheimer Proteins APP and LRP.

PMID- 27690591
TI  - Mitochondrial Dynamics in Synaptic Plasticity in Drosophila melanogaster.

PMID- 27690592
TI  - Gill and Lung Rhythm in the Late-Stage Tadpole Rana catesbeiana.

PMID- 27690594
TI  - Alkaline Phosphatase Activity in the Toxic Dinoflagellate Karenia brevis.

PMID- 27690593
TI  - The Time Course of the Camouflage Response of Cuttlefish (Sepia officinalis).

PMID- 27690595
TI  - Spatial Distribution of Land Type in Regression Models of Pollutant Loading.

PMID- 27690596
TI  - Histochemical Evidence for Lipopolysaccharide (Endotoxin) in Eukaryotes.

PMID- 27690597
TI  - Histidine Suppresses Zinc Modulation of Connexin Hemichannels Expressed in
      Xenopus Oocytes.

PMID- 27690598
TI  - Nitrate Reductase and Glutamine Synthetase Activity and Growth in Ulva lactuca in
      Waquoit Bay: A Time Sequence of Responses to Differences in Nitrogen Supply.

PMID- 27690599
TI  - Effect of Nutrient Enrichment and Salinity on Salt Marsh Invertebrates in the
      Plum Island Estuary.

PMID- 27690600
TI  - Characterization of Bacteria Associated With Lobster Shell Disease.

PMID- 27690601
TI  - Development of a Global Collaborative Taxonomic Name Service for the Location and
      Retrieval of Electronic Resources in Biology.

PMID- 27690602
TI  - Estimating Groundwater-Derived Nitrogen Flux Into a Coastal Embayment: Salt Pond,
      Cape Cod, Massachusetts.

PMID- 27690603
TI  - Cis Editing in Trypanosoma brucei brucei as a Model for Understanding Guide-RNA
      Structural and Functional Requirements.

PMID- 27690604
TI  - Cell Division Dynamics of Drosophila Kc Cells Without Functional Mitotic
      Centrosomes.

PMID- 27690605
TI  - MAP Kinase Expression Correlates With the Posterior Midline in Early Cleavage
      Stage Squid Embryos.

PMID- 27690606
TI  - Imaging Patterns of Ca2+ Transients During the Blastula Period in Zebrafish
      Embryos.

PMID- 27690607
TI  - Role of Ca2+ Signaling During Early Pronephric Development in Zebrafish and
      Xenopus Embryos.

PMID- 27690608
TI  - Evolution of Myelin Proteins.

PMID- 27690609
TI  - Disruptive Body Patterning of Cuttlefish (Sepia officinalis) Requires Visual
      Information on Edges and Brightness of Objects on Natural Substrate Backgrounds.

PMID- 27690610
TI  - Characterization of the Myostatin-Like Gene in Argopecten irradians.

PMID- 27690611
TI  - Immunocytochemical Detection of Integrins alpha3 and beta1 in Allografts of the
      Marine Sponge, Microciona prolifera.

PMID- 27690612
TI  - Actin-Mediated Retrograde Flow in Sea Urchin Coelomocytes: Conversion From a
      Lamellipodial-Dominated to a Filopodial-Dominated Form.

PMID- 27690614
TI  - Identification of Novel Myosin-V Binding Partners by Immunoprecipitation and
      Column Chromatography.

PMID- 27690613
TI  - Initial Sequence and Protein Modeling Results of a Mitochondrial Genome Project
      on Understudied Invertebrate Phyla.

PMID- 27690615
TI  - Role of Rab GTPases in Recruitment of Myosin- V to Vesicles of Squid Giant Axon.

PMID- 27690616
TI  - Marine Plants May Polarize Remote Fucus Eggs via Luminescence.

PMID- 27690618
TI  - Errata.

PMID- 27690617
TI  - Young adults perinatally infected with HIV perform more poorly on measures of
      executive functioning and motor speed than ethnically matched healthy controls.
AB  - Perinatal HIV is associated with significant neurocognitive morbidities, but few
      studies have examined cognitive impact of early HIV infection on patients
      surviving to adulthood. The purpose of this study was to evaluate neurocognitive
      outcomes among a cohort of perinatally infected young adults. Individuals between
      the ages of 18 and 24 with perinatal infection were recruited for this cross
      sectional study along with similarly aged healthy controls. Participants
      completed an MRI and brief neuropsychological assessment battery. Multivariate
      analysis of covariance controlling for age, gender, race/ethnicity, and education
      was completed to detect differences between the HIV+ and control groups.
      Multivariable linear regression was performed to assess HIV-associated factors
      potentially impacting neuropsychological findings among the HIV+ group. Twenty
      nine HIV+ young adults and 13 healthy controls were included in the study. After
      adjusting for age and sociodemographic variables, the HIV+ group scored lower on
      attention/working memory (Digit Span (p = .008) and Letter-Number Sequencing (p =
      .038)), set-shifting (DKEFS Trail Making Test Condition 4 (p = .026) and motor
      speed (DKEFS Trail Making Test Condition 5 (p = .003)). For the HIV+ group, nadir
      CD4 was associated with better Letter-Number Sequencing score (p = .029) and use
      of highly active antiretroviral therapy was associated with better performance on
      Category Fluency (p = .040). After controlling for sociodemographic variables,
      executive dysfunction persists among young adults with perinatal HIV infection in
      comparison to controls. Future studies to further elucidate the impact of
      executive dysfunction on independent living and functional outcomes are
      indicated.

PMID- 27690620
TI  - [Change in our approach in the surgical management of congenital heart defects in
      patients with Down syndrome, 1974-2016].
AB  - INTRODUCTION: Congenital heart defects are frequently present in patients with
      Down syndrome. AIM: The authors analyzed the impact of changing approach in
      surgical management of congenital heart defect on the life expectancy of patients
      with Down syndrome. METHOD: Between 1974 and 1997 the data of 359 children with
      Down syndrome were collected. Among them 255 patients had no surgery and the
      mortality in this group was 25.9%, whereas the mortality in the group of 104
      patients who underwent palliative surgery was 8.6%. RESULTS: Surgical management
      of congenital heart defects provides the same life expectancy for these patients
      as compared to Down patients without cardiac defects. Primary reconstruction is
      the preferable surgical procedure in infancy that provides good results. Nowadays
      the number of the operated grown-up congenital heart disease patients with Down
      syndrome is increasing. During the last three years 82 grown-up congenital heart
      disease patients, including 4 patients with Down syndrome (aged between 24 and 60
      years) were reconstructed successfully. CONCLUSIONS: Due to the successful
      surgery in infancy the population of grown-up congenital heart disease patients
      with Down syndrome is increasing. The cardiac surgeons are ready to do everything
      for the optimal life expectancy of these patients. However, management of special
      problems (indication and necessity of reoperation, optimal age) in patients with
      Down syndrome poses a great challenge for cardiologists and cardiac surgeons.
      Orv. Hetil., 2016, 157(40), 1601-1603.

PMID- 27690619
TI  - Characteristics of intermittent smokers and their association with quit
      intentions in a sample of heavy-drinking HIV-infected men who have sex with men.
AB  - Intermittent smokers (ITS) have increased health risks compared with non-smokers
      (NS). Cigarette smoking remains prevalent among men who have sex with men (MSM)
      and persons living with HIV (PLWH), yet most studies in PLWH do not discriminate
      between daily smokers (DS) and ITS. In this study, the characteristics and quit
      intentions of ITS and DS are compared in a sample of heavy-drinking HIV-infected
      MSM. Of the 185 participants enrolled, 49.2% reported having smoked cigarettes in
      the past month; among those, 50.5% were DS, and 49.5% were ITS. Compared with DS,
      ITS were significantly more likely to be White and to have a college degree or
      higher. DS reported significantly higher average number of drinks per week
      compared with both ITS and NS. Compared with DS, ITS were significantly more
      likely to report future quit intentions (i.e., within 6 months or more) compared
      to no intentions at all; DS were more likely to report immediate quit intentions
      (i.e., within 30 days) compared to future quit intentions. Among heavy-drinking
      MSM living with HIV, intermittent smoking was associated with being White,
      college educated, and having future quit intentions. Considering that smoking in
      ITS may be less driven by nicotine dependence, tailored approaches to smoking
      cessation may be needed. Specifically, it may be important for interventions for
      ITS to address social and situational cues to smoke, including the influence of
      heavy alcohol use on smoking behaviors, and to provide information regarding the
      adverse health effects of even low-level smoking.

PMID- 27690621
TI  - [A rare zoonosis in Hungary: cercarial dermatitis caused by Schistosoma
      turkestanicum blood-fluke].
AB  - Several trematodes that parasitize vertebrate animals utilize swimming aquatic
      larvae to infect the host percutaneously. The most important ones among these
      parasites are the blood-flukes of birds and mammals comprising species that are
      also zoonotic. Within this latter group are species that cause the bilharziasis
      or schistosomiasis of inhabitants of the tropical countries, and other trematode
      species that are able to penetrate human skin, but do not develop to an adult
      form of the worm in the body. In temperate climates this latter type of infection
      occurs mainly in the form of an unpleasant inflammation of the skin and is often
      called "swimmer's itch". In most of these cases, the origin of the larvae remains
      unexplored, the source of the infection is neglected by the medical or
      veterinarian practitioners. Herein we report for the first time in Hungary that
      the cause of such dermatitis was the cercariae of Schistosoma turkestanicum,
      which infected red deer (Cervus elaphus) in this country. The local name of this
      pristine disease is "water mange" and it occurs only in one of the floodplains of
      the Danube. On the basis of informal communication this symptom seems to be
      rather regular among people who do fishing or have a bath in the habitat of the
      blood-fluke. In the case of adequate anamnesis it is worth examining the origin
      of the cercarial dermatitis which may give cross-reactions with human
      schistosomiasis during serological tests. Orv. Hetil., 2016, 157(40), 1579-1586.

PMID- 27690623
TI  - [Abstracts of lectures to be presented at the 2016 Annual Congress of the
      Hungarian Society of Clinical Nutrition. Matrahaza, Lifestyle Hotel Matra,
      October 6-8, 2016].

PMID- 27690622
TI  - [Ramucirumab - a new anticancer agent].
AB  - Ramucirumab is a humanized monoclonal antibody against vascular endothelial
      growth factor receptor-2, which inhibits the binding of vascular endothelial
      growth factor-A, -C and -D ligands. Furthermore it blocks the ligand stimulated
      activation of p44/p42 mitogen activated protein kinases, thus neutralizing the
      ligand induced proliferation and migration of human endothelial cells. Based on
      the results of the REGARD (Ramucirumab monotherapy for previously treated
      advanced gastric or gastro-oesophageal junction adenocarcinoma) and the RAINBOW
      (Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with
      previously treated advanced gastric or gastro-oesophageal junction
      adenocarcinoma) studies ramucirumab was approved for 2nd line treatment as
      monotherapy and in combination with paclitaxel for patients with local relapse
      and unresectable or metastatic gastric cancer (including gastro-esophegal
      junction adenocarcinoma). Based on the results, in advanced solid malignancies,
      ramucirumab may prolong progression free survival and overall survival, although
      it may increase the risk of all adverse events (fatigue, neutropenia,
      haemorrhage, nausea, stomatitis). The authors review the clinical studies of
      ramucirumab. Orv. Hetil., 2016, 157(40), 1587-1594.

PMID- 27690624
TI  - [Active euthanasia, or assisted suicide?]
AB  - INTRODUCTION: Both active euthanasia and assisted suicide are legal in The
      Netherlands, Belgium, Luxemburg and, most recently, in Canada. AIM: Examination
      of national legislations of countries where both active euthanasia and assisted
      suicide are legal. The number of accomplished active euthanasia cases and that of
      assisted suicide cases. METHOD: Analysis of national statistical data. Comparison
      of statistical data before and after 2010. Comparison of the related practices in
      the surveyed countries. RESULTS: The number of active euthanasia cases markedly
      predominates over the number of assisted suicide cases. Cancer is a main reason
      for active euthanasia, or assisted suicide. In countries with a larger
      population, the number of active euthanasia cases is higher than that in
      countries with a smaller population. CONCLUSIONS: Regarding the fact that the
      applicants for active euthanasia withdraw their requests in a smaller number than
      the applicants for assisted suicide, patients prefer the choice of active
      euthanasia. Since the related legislative product is too recent in Canada at
      present, it may be only presumed that a certain preference will also develop in
      the related practices in Canada. Orv. Hetil., 2016, 157(40), 1595-1600.

PMID- 27690625
TI  - [Miscellaneous].

PMID- 27690626
TI  - The Andrea Yates Effect: Priming Mental Illness Stereotypes Through
      Exemplification of Postpartum Disorders.
AB  - In a randomized between-subjects design, participants (N = 80) were assigned to
      one of four conditions, 2 (pregnant, not pregnant) * 2 (extreme prime, moderate
      prime). It was hypothesized that primes involving moderate mental illness would
      be positively associated with increased perceived risk of developing postpartum
      depression. Hayes and Preacher's bootstrapping procedure was used to test the
      direct, indirect, and conditional indirect effects related to the hypothesized
      model. In addition, further analyses evaluated whether implicitly activated goals
      (to be healthy or to be a good mother) were positively associated with increased
      perceptions of risk and engagement of downstream avoidance behavioral intentions.
      Findings show that for pregnant participants, the effect of the prime condition
      on perceived personal risk of developing postpartum depression was mediated by
      perceptions about the target character's sanity. However, activated "healthy" and
      "good mother" goals are not influencing behavioral intentions.

PMID- 27690627
TI  - One new flavanocoumarin from the thorns of Gleditsia sinensis.
AB  - One new flavanocoumarin (1), as well as six known flavonoids (2-7), was isolated
      from the ethyl acetate extract of the thorns of Gleditsia sinensis. The
      structures of these compounds were elucidated by extensive spectroscopic
      measurements and comparison with data reported in literatures. Cytotoxic
      activities of compounds 1-6 were evaluated against human liver cancer SK-hep-1
      cells in vitro by the MTT method, with compound 1 displaying moderate activity
      (IC50 of 62.53 MUM). Furthermore, compound 1 could increase the number of
      apoptosis cells in a concentration-dependent manner.

PMID- 27690628
TI  - Synthesis and antioxidant activity of curcumin analogs.
AB  - Numerous biological activities including antioxidant, antitumor, anti
      inflammation, and antivirus of the natural product curcumin were reported.
      However, the clinical application of it was significantly limited by its
      instability, poor solubility, less body absorbing, and low bioavailability. This
      review focuses on the structure modification and antioxidant activity evaluation
      of curcumin. To study the structure-activity relationship (SAR), five series of
      curcumin analogs were synthesized and their antioxidant activity were evaluated
      in vitro. The results showed that electron-donating groups, especially the
      phenolic hydroxyl group are an essential component to improve the antioxidant
      activity.

PMID- 27690629
TI  - Optimizing antifungal strategies to improve patient survival.
AB  - Report from the 26th European Congress of Clinical Microbiology and Infectious
      Diseases (ECCMID 2016), 9-12 April Amsterdam, The Netherlands Invasive fungal
      infections are a major threat to the lives of the increasing number of
      immunocompromized patients, but neutropenic hemato-oncology patients are at
      especially high risk. Since effective antifungal treatment and prophylaxis are
      critical to improve survival in these patients, the emergence of antifungal drug
      resistance has become an increasing cause of concern. Mortality from invasive
      fungal infection also remains high even when patients receive appropriate and
      timely antifungal therapy. These important topics were among those discussed by
      the over 11,600 clinical microbiologists and infectious disease physicians from
      more than 120 countries attending the 26th European Congress of Clinical
      Microbiology and Infectious Diseases.

PMID- 27690630
TI  - Examining How Racial Discrimination Impacts Sleep Quality in African Americans:
      Is Perseveration the Answer?
AB  - BACKGROUND: African Americans experience more problematic and disordered sleep
      than White Americans. Racial discrimination has been implicated in this
      disparity. However, the mechanisms by which discrimination disrupts sleep are
      unclear. It has been theorized that Perseverative Cognition (PC), characterized
      by recurrent patterns of reflective (i.e., rumination) and anticipatory (i.e.,
      worry) negative thinking about personally relevant stressors, may reflect the
      functional mechanism linking discrimination to sleep. The present study is the
      first to empirically examine the dual components of PC as a candidate functional
      mechanism in the association between racial discrimination and subjective sleep
      quality. PARTICIPANTS: Sixty-eight self-identified African American college
      students (55.9% female; Mage = 20.18, SD = 2.93) were recruited at a large
      predominantly white public university in the Midwest. METHODS: The participants
      completed the Perceived Ethnic Discrimination Questionnaire (PEDQ), Pittsburgh
      Sleep Quality Index (PSQI), Penn State Worry Questionnaire (PSWQ), and Ruminative
      Responses Scale (RRS). RESULTS: After adjusting for age, gender, and social
      class, results revealed a significant indirect effect of racial discrimination
      (RD) on subjective sleep quality through rumination, 95% CI [.008, .125], but not
      worry. RD was positively associated with rumination, b =.50, SE =.16, p = .003,
      and rumination, in turn, was positively associated with poorer sleep quality, b =
      .09, SE = .04, p = .012. CONCLUSIONS: As both RD and poor sleep quality have been
      directly linked to heart disease, diabetes, depression, and a number of other
      maladies, our findings suggest that RD, sleep, and coping strategies (e.g.,
      rumination) employed to manage RD experiences may be important targets for
      addressing racial disparities in health.

PMID- 27690632
TI  - 3D CT scan for perioperative identification of anatomical variations of lungs.
AB  - AIM: The aim of this study is to investigate anatomical lung variations and
      vascular patterns using volumetric 3D computed tomography (CT) representations.
      METHODS & RESULTS: We considered 24 major thoracic surgery performed in our ward.
      In these, we discovered some interesting anatomical variations of the main
      pulmonary fissures. These findings were not visible on the plain x-ray or during
      routine examination of a preoperative CT scan. After re-examination of 3D CT scan
      reconstruction the anatomical variations were detected. DISCUSSION: General
      thoracic surgeons must familiarize themselves with anatomical variations in
      lungs. 3D images may aid the general thoracic surgeon in performing safer
      surgeries. CONCLUSION: 3D CT scan should be performed before surgery if possible.

PMID- 27690631
TI  - HOTAIR rs920778 polymorphism is associated with ovarian cancer susceptibility and
      poor prognosis in a Chinese population.
AB  - AIM: The aim of this study was to determine if HOTAIR rs920778 polymorphism is
      associated with ovarian cancer susceptibility and prognosis. MATERIALS & METHODS:
      The data were obtained from two independent groups including 329 ovarian cancer
      patients and 680 cancer-free, age-matched women. Blood samples were collected and
      genomic DNA was extracted for genotyping. RESULTS: TT genotype and T allele of
      HOTAIR rs920778 were significantly associated with a decreased ovarian cancer
      risk (p = 0.0004 and p < 0.0001, respectively), which associated with advanced
      tumor stage, lymph node metastasis and poor prognosis. Moreover, TT and TC
      carriers obtained a much shorter survival (p = 0.026). CONCLUSION: These findings
      propose that HOTAIR rs920778 polymorphism influences ovarian cancer
      susceptibility and prognosis, and further studies are warranted in other
      populations.

PMID- 27690633
TI  - A new flavonol glycoside from the aerial parts of Epimedium koreanum Nakai.
AB  - A new prenylated flavonol glycoside (1) was isolated from a 95% methanol extract
      of the dried and powdered aerial parts of Epimedium koreanum Nakai (Herba
      Epimedii), along with seven previously known flavonoids (2-8). The chemical
      structure of the new compound (1) was established to be 5-hydroxy-4'-methoxy-8-(2
      hydroxy-3-methyl-3-butenyl)flavone 3-O-alpha-l-rhamnopyranosyl-7-O-beta-D-gluco
      pyranoside on the basis of spectroscopic methods. The antioxidant activities of
      these compounds were determined by the DPPH (2,2-diphenyl-1-picrylhydrazyl) free
      radical scavenging assay and kaempferitrin (8) showed a high reactivity with
      DPPH.

PMID- 27690635
TI  - Development and Evaluation of the Sugar-Sweetened Beverages Media Literacy (SSB
      ML) Scale and Its Relationship With SSB Consumption.
AB  - Understanding how adults' media literacy skill sets impact their sugar-sweetened
      beverage (SSB) intake provides insight into designing effective interventions to
      enhance their critical analysis of marketing messages and thus improve their
      healthy beverage choices. However, a media literacy scale focusing on SSBs is
      lacking. This cross-sectional study uses baseline data from a large randomized
      controlled trial to (a) describe the psychometric properties of an SSB Media
      Literacy Scale (SSB-ML) scale and its subdomains, (b) examine how the scale
      varies across demographic variables, and (c) explain the scale's concurrent
      validity to predict SSB consumption. Results from 293 adults in rural
      southwestern Virginia (81.6% female, 94.0% White, 54.1% receiving SNAP and/or WIC
      benefits, average 410 SSB kcal daily) show that overall SSB-ML scale and its
      subdomains have strong internal consistencies (Cronbach's alphas ranging from
      0.65 to 0.83). The Representation & Reality domain significantly predicted SSB
      kilocalories, after controlling for demographic variables. This study has
      implications for the assessment and inclusion of context-specific media literacy
      skills in behavioral interventions.

PMID- 27690636
TI  - Reducing Resistance to Narrative Persuasion About Binge Drinking: The Role of
      Self-Activation and Habitual Drinking Behavior.
AB  - This study explores the effects of habitual health risk behaviors and self
      activation on resistance to narrative persuasion. In two experiments, heavier
      drinkers were more resistant to an anti-binge-drinking narrative public service
      announcement (PSA) in which a binge drinker suffers a negative outcome.
      Specifically, heavier drinkers were more likely to generate counterarguments,
      unrealism judgments, and negative evaluations about the message compared to
      lighter drinkers or nondrinkers. However, activating self-concept when processing
      the persuasive narrative reduced unrealism judgments and negative evaluations,
      particularly among heavier drinkers. Self-activation also decreased perceived
      freedom threat among both heavier and lighter drinkers, which further led to
      higher perceived risk of binge drinking. Theoretical and practical implications
      are discussed.

PMID- 27690634
TI  - Caregiving-Related Sleep Problems and Their Relationship to Mental Health and
      Daytime Function in Female Veterans.
AB  - OBJECTIVE/BACKGROUND: To identify caregiving-related sleep problems and their
      relationship to mental health and daytime function in female Veterans.
      PARTICIPANTS: Female Veterans (N = 1,477) from cross-sectional, nationwide,
      postal survey data. METHODS: The survey respondent characteristics included
      demographics, comorbidity, physical activity, health, use of sleep medications,
      and history of sleep apnea. They self-identified caregiving- related sleep
      problems (i.e., those who had trouble sleeping because of caring for a sick
      adult, an infant/child, or other respondents). Patient Health Questionnaire (PHQ
      4) was used to assess mental health, and daytime function was measured using 11
      items of International Classification of Sleep Disorders-2 (ICSD-2). RESULTS:
      Female Veterans with self-identified sleep problems due to caring for a sick
      adult (n = 59) experienced significantly more symptoms of depression and anxiety
      (p < 0.001) and impairment in daytime function (e.g., fatigue, daytime
      sleepiness, loss of concentration, p < 0.001) than those with self-identified
      sleep problems due to caring for an infant or child (n = 95) or all other
      respondents (n = 1,323) after controlling for the respondent characteristics.
      CONCLUSIONS: Healthcare providers should pay attention to assessing sleep
      characteristics of female Veterans with caregiving responsibilities, particularly
      those caregiving for a sick adult.

PMID- 27690637
TI  - Referential communication abilities in children with 22q11.2 deletion syndrome.
AB  - PURPOSE: This study describes the performance on a perspective- and role-taking
      task in 27 children, ages 6-13 years, with 22q11.2 deletion syndrome (22q11.2DS).
      A cross-cultural design comparing Dutch- and English-speaking children with
      22q11.2DS explored the possibility of cultural differences. METHOD:
      Chronologically age-matched and younger typically developing (TD) children
      matched for receptive vocabulary served as control groups to identify challenges
      in referential communication. RESULTS: The utterances of children with 22q11.2DS
      were characterised as short and simple in lexical and grammatical terms. However,
      from a language use perspective, their utterances were verbose, ambiguous and
      irrelevant given the pictured scenes. They tended to elaborate on visual details
      and conveyed off-topic, extraneous information when participating in a barrier
      game procedure. Both types of aberrant utterances forced a listener to
      consistently infer the intended message. Moreover, children with 22q11.2DS
      demonstrated difficulty selecting correct speech acts in accordance with
      contextual cues during a role-taking task. CONCLUSION: Both English- and Dutch
      speaking children with 22q11.2DS showed impoverished information transfer and an
      increased number of elaborations, suggesting a cross-cultural syndrome-specific
      feature.

PMID- 27690638
TI  - Effectively Coping With Task Stress: A Study of the Validity of the Trait
      Emotional Intelligence Questionnaire-Short Form (TEIQue-SF).
AB  - In this study, we investigated the validity of the Trait Emotional Intelligence
      Questionnaire-Short Form (TEIQue-SF; Petrides, 2009) in the context of task
      induced stress. We used a total sample of 225 volunteers to investigate (a) the
      incremental validity of the TEIQue-SF over other predictors of coping with task
      induced stress, and (b) the construct validity of the TEIQue-SF by examining the
      mechanisms via which scores from the TEIQue-SF predict coping outcomes. Results
      demonstrated that the TEIQue-SF possessed incremental validity over the Big Five
      personality traits in the prediction of emotion-focused coping. Results also
      provided support for the construct validity of the TEIQue-SF by demonstrating
      that this measure predicted adaptive coping via emotion-focused channels.
      Specifically, results showed that, following a task stressor, the TEIQue-SF
      predicted low negative affect and high task performance via high levels of
      emotion-focused coping. Consistent with the purported theoretical nature of the
      trait emotional intelligence (EI) construct, trait EI as assessed by the TEIQue
      SF primarily enhances affect and performance in stressful situations by
      regulating negative emotions.

PMID- 27690639
TI  - Discard the Smoking Cues-Keep the Disgust: An Investigation of Tobacco Smokers'
      Motivated Processing of Anti-tobacco Commercials.
AB  - This study experimentally examines the effect of smoking cues and disgust images
      commonly found in anti-tobacco advertisements on tobacco smokers' message
      processing. In a 2 (smoking cues) * 2 (disgust) within-subjects experiment,
      smokers watched anti-tobacco advertisements selected to vary in presence/absence
      of smoking cues and high/low ratings of disgust. The results of the experiment
      suggest that smoking cues and disgust images each have effects on resource
      allocation, recognition memory, emotional responses, smoking urges, and
      intentions to quit smoking. However, the most notable finding in this study was
      how the combination of smoking cues and disgust images in a single anti-tobacco
      message resulted in defensive message processing. Theoretical and applied
      implications of these findings are discussed along with future research
      directions.

PMID- 27690640
TI  - Role of catalase overproduction in drug resistance and virulence in Candida
      albicans.
AB  - AIM: To investigate the role of Cat1 overproduction in Candida albicans.
      MATERIALS & METHODS: Strains overproducing the CAT1 gene were constructed.
      RESULTS: Cells overproducing CAT1 were found to be more resistant to some
      oxidants and mammalian phagocytic cells. They also showed reduced intracellular
      reactive oxygen species generated by amphotericin B or ciclopirox olamine. CAT1
      overproduction did not change the minimum inhibitory concentration of fungal
      cells to fungistatic or fungicidal azoles nor to amphotericin B although
      increased twofold the minimum inhibitory concentration to caspofungin. The role
      of Cat1 overproduction in virulence and colonization was also analyzed in mouse
      models. CONCLUSION: The overproduction of Cat1 protects against oxidants,
      phagocytes and certain antifungals at subinhibitory concentration but does not
      increase virulence in a systemic infection mouse model.

PMID- 27690641
TI  - Chemical constituents of Cinnamomum septentrionale leaf litter and its
      allelopathic activity on the growth of maize (Zea mays).
AB  - A pot experiment was conducted to study the effect of decomposing Cinnamomum
      septentrionale leaf litter on the growth of maize. In this study, the
      morphological traits of maize were significantly inhibited when the leaf litter
      amount reached or exceeded 40 g per pot; Furthermore, during the early growth
      stage or with a large amount of litter addition, the pigment contents were
      inhibited by C. septentrionale leaf litter. Gas chromatography-mass spectrometry
      was used to determine the volatile substances of leaf litter and 34 compounds
      were identified, several of which were reported to be phytotoxic. In conclusion,
      the leaf litter of C. septentrionale showed a strong allelopathic effect on the
      growth of maize. Thus, it is better to avoid the growing of maize under or near
      the C. septentrionale plantation unless the leaf litter could be eliminated in
      time or other effective leaf litter processing methods could be implemented.

PMID- 27690642
TI  - Regulatory T CD4 + CD25+ lymphocytes increase in symptomatic carotid artery
      stenosis.
AB  - BACKGROUND: Atherosclerosis is a multifactorial disease characterized by an
      immune-inflammatory remodeling of the arterial wall. Treg and Th17 subpopulations
      are detectable inside atherosclerotic plaque; however, their behavior in
      symptomatic carotid artery stenosis (CAS) is not fully elucidated. The aim of
      this study was to evaluate Th17 and Treg subsets and their ratio in patients
      affected by symptomatic and asymptomatic CAS. METHODS: 14 patients with
      symptomatic CAS (CAS-S group), 41 patients with asymptomatic CAS (CAS-A group),
      32 subjects with traditional cardiovascular risk factors (RF group), and 10
      healthy subjects (HS group) were enrolled. Th17 and Treg frequency was determined
      by flow cytometry and by histology and immunohistochemistry. Interleukin (IL)-10,
      IL-17, and metalloproteinase (MMP)-12 levels were measured by ELISA. RESULTS:
      Th17 were significantly increased in CAS-A versus RF and versus HS. Tregs were
      significantly increased in CAS-S versus CAS-A. Tregs/Th17 ratio was significantly
      reduced in CAS-A versus RF and versus HS, whereas it was significantly increased
      in CAS-S versus CAS-A. CONCLUSIONS: The results of this study suggest that Th17
      are related to the late stages of CAS but not to plaque instability. Moreover,
      Treg expansion seems to represent a specific cellular pattern displayed by
      patients with symptomatic CAS and associated with brain injury. KEY MESSAGES
      Tregs expansion seems to represent a specific cellular pattern displayed by
      patients with symptomatic CAS and associated with CD4+ effector depletion and
      brain ischemic injury. Th17 lymphocytes are related to the late stages of CAS but
      not to plaque instability.

PMID- 27690643
TI  - Helsinn: 20 years in primary cancer supportive care.
AB  - Sergio Cantoreggi speaks to Henry Ireland, Commissioning Editor: Sergio
      Cantoreggi, PhD, is the Chief Scientific Officer and Global Head of Research and
      Development of the Helsinn Group, a mid-sized pharmaceutical company
      headquartered in Lugano, Switzerland, and focused on providing cancer supportive
      care solutions to oncology patients worldwide. Dr Cantoreggi has overall
      responsibility for all R&D activities of the Helsinn Group and has contributed to
      six major regulatory approvals of cancer supportive care agents in the USA,
      Europe and Japan. Dr Cantoreggi joined Helsinn Healthcare in 2000 as drug
      development scientist and was appointed Head of R&D in 2005. In 2010, he was
      promoted to his current role. From 1994 to 2000 he worked as toxicologist and
      regulatory scientist for Du Pont, Sandoz and Novartis. Prior to joining industry,
      Dr Cantoreggi completed a postdoctoral fellowship and earned a Master of Science
      degree in chemistry and a Doctoral degree in natural sciences with a thesis on
      the mechanism of chemical carcinogenesis from the Swiss Federal Institute of
      Technology in Zurich, Switzerland. Sergio Cantoreggi discusses Helsinn's role in
      cancer supportive care, describing current treatment options for patients, the
      company's pipeline and Helsinn's work in supporting the field as a whole.

PMID- 27690644
TI  - Isolation, structure elucidation, and induction of hepatoma cell apoptosis of
      abietane diterpenoids from Abies faxoniana.
AB  - Two new abietane diterpenoids (1-2) and 13 known compounds (3-15) were
      characterized from the branches and leaves of Abies faxoniana. The chemical
      structures of the new diterpenoids (1-2) were determined through the analysis of
      various 1D/2D NMR techniques. Compound 3 is 151,617-trinor-abietane diterpenoid
      conjugated with a three-membered epoxide ring. The isolated diterpenoids were
      tested for their cytotoxicities. Among them, compound 3 exhibited the strongest
      antiproliferative effect against human hepatoma cell SMMC7721 with an IC50 value
      of 12.5 MUM. To elucidate the preliminary mechanism responsible for compound 3
      induced inhibition of cell proliferation, we investigated the effects of compound
      3 on apoptosis, cell cycle progression, and reactive oxygen species generation in
      SMMC7721 cells. The results showed that compound 3 induced cell apoptosis and
      excessive ROS production, but did not change the cell cycle distribution in
      SMMC7721 cells.

PMID- 27690645
TI  - Augmenting effect of vitrification on lipid peroxidation in mouse preantral
      follicle during cultivation: Modulation by coenzyme Q10.
AB  - Cryopreservation-induced oxidative stress (OS) may lead to lipid peroxidation,
      which may be responsible for decreased cell survival rate. Coenzyme Q10 (CoQ10)
      as a potent antioxidant may improve cell viability by neutralizing OS. In this
      study, oxidative lipid injury following the vitrification of preantral follicles
      was investigated. The effects of CoQ10 treatment on the malondialdehyde (MDA)
      levels, lipid peroxidation products, and activities of enzymatic and nonenzymatic
      antioxidants of vitrified preantral follicles were also studied. Preantral
      follicles were isolated from immature mouse ovaries and were vitrified. After
      warming, these follicles were cultured with or without CoQ10 for four days. The
      levels of total antioxidant capacity (TAC) and MDA, as well as the activities of
      superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT),
      were assessed at 0, 24, 48, 72, and 96 hours of culture period. The MDA level in
      the vitrified preantral follicles was higher than that in the fresh groups. By
      contrast, the MDA level was significantly lower in the groups with CoQ10
      treatment than in those without this treatment during cultivation. The TAC level
      was higher in the fresh preantral follicles than in the vitrified groups. The
      rates were also higher in the CoQ10-treated groups than in those without this
      treatment. The activities of SOD, GPX, and CAT were also significantly higher in
      the fresh groups than in the vitrified groups, especially in the groups with
      CoQ10 treatment than in those without this treatment. Lowering the vitrification
      induced lipid peroxidation of preantral follicles by CoQ10-supplemented
      maturation medium may be mediated by increasing SOD, GPX, and CAT activities and
      TAC level during cultivation.

PMID- 27690646
TI  - Laser interstitial thermal therapy for subependymal giant cell astrocytoma:
      technical case report.
AB  - Subependymal giant cell astrocytoma (SEGA) is a rare tumor occurring almost
      exclusively in patients with tuberous sclerosis complex. Although open resection
      remains the standard therapy, complication rates remain high. To minimize
      morbidity, less invasive approaches, such as endoscope-assisted resection,
      radiosurgery, and chemotherapy with mTOR pathway inhibitors, are also used to
      treat these lesions. Laser interstitial thermal therapy (LITT) is a relatively
      new modality that is increasingly used to treat a variety of intracranial
      lesions. In this report, the authors describe two pediatric cases of SEGA that
      were treated with LITT. In both patients the lesion responded well to this
      treatment modality, with tumor shrinkage observed on follow-up MRI. These cases
      highlight the potential of LITT to serve as a viable minimally invasive
      therapeutic approach to the management of SEGAs in the pediatric population.

PMID- 27690647
TI  - Letter to the Editor: Identification of residual glioma using ultrasound
      miniprobes.

PMID- 27690648
TI  - Safety of stereotactic laser ablations performed as treatment for glioblastomas
      in a conventional magnetic resonance imaging suite.
AB  - OBJECTIVE Stereotactic laser ablation (SLA) is typically performed in the setting
      of intraoperative MRI or in a staged manner in which probe insertion is performed
      in the operating room and thermal ablation takes place in an MRI suite. METHODS
      The authors describe their experience, in which SLA for glioblastoma (GBM)
      treatment was performed entirely within a conventional MRI suite using the
      SmartFrame stereotactic device. RESULTS All 10 patients with GBM (2 with
      isocitrate dehydrogenase 1 mutation [mIDH1] and 8 with wild-type IDH1 [wtIDH1])
      were followed for > 6 months. One of these patients underwent 2 independent SLAs
      approximately 12 months apart. Biopsies were performed prior to SLA for all
      patients. There were no perioperative morbidities, wound infections, or unplanned
      30-day readmissions. The average time for a 3-trajectory SLA (n = 3) was 436 +/-
      102 minutes; for a 2-trajectory SLA (n = 4) was 321 +/- 85 minutes; and for a
      single-trajectory SLA (n = 4) was 254 +/- 28 minutes. No tumor recurrence
      occurred within the blue isotherm line ablation zone, although 2 patients
      experienced recurrence immediately adjacent to the blue isotherm ablation line.
      Overall survival for the patient cohort averaged 356 days, with the 2 patients
      who had mIDH1 GBMs exhibiting the longest survival (811 and 654 days).
      CONCLUSIONS Multitrajectory SLA for treatment of GBM can be safely performed
      using the SmartFrame stereotactic device in a conventional MRI suite.

PMID- 27690649
TI  - The use of custom 3D printed stereotactic frames for laser interstitial thermal
      ablation: technical note.
AB  - Over the last several years, laser interstitial thermotherapy (LITT) has gained
      wide acceptance for the treatment of a myriad of cranial lesions. A wide variety
      of techniques for placement of the laser fiber have been reported with a spectrum
      of perceived benefits and drawbacks. The authors present the first report of a
      customized 3D printed stereotactic frame for LITT. Approximately 1 week prior to
      surgery, 3-4 skull fiducials were placed after each of 5 patients received a
      local anesthetic as an outpatient. Radiographs with these fiducials were then
      used to create a trajectory to the lesion that would be treated with LITT. After
      the plan was completed, software was used to render a customized frame. On the
      day of surgery, the frame was attached to the implanted skull fiducials and the
      LITT catheter was placed. This procedure was carried out in 5 consecutive
      patients. In 2 patients, a needle biopsy was also performed. Intraoperative and
      postoperative imaging studies confirmed the accurate placement of the LITT
      catheter and the lesion created. Mean operating room time for all patients was 45
      minutes but only 26 minutes when excluding the cases in which a biopsy was
      performed. To the best of the authors' knowledge, this is the first report of the
      use of a specific system, the STarFix microTargeting system, for use with LITT
      and brain biopsy. This system offers several advantages including fast operating
      times, extensive preoperative planning, no need for cranial fixation, and no need
      for frame or fiducial placement on the day of surgery. The accuracy of the system
      combined with these advantages may make this a preferred stereotactic method for
      LITT, especially in centers where LITT is performed in a diagnostic MRI suite.

PMID- 27690650
TI  - Introduction: Laser ablation techniques.

PMID- 27690651
TI  - Magnetic resonance imaging-guided laser interstitial thermal therapy for
      previously treated hypothalamic hamartomas.
AB  - OBJECTIVE Hypothalamic hamartomas (HHs) are associated with gelastic seizures and
      the development of medically refractory epilepsy. Magnetic resonance imaging
      guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive
      ablative treatment that may have applicability for these deep-seated lesions.
      Here, the authors describe 3 patients with refractory HHs who they treated with
      MRg-LITT. METHODS An institutional review board-approved prospective database of
      patients undergoing Visualase MRg-LITT was retrospectively reviewed. Demographic
      and historical medical data, including seizure and medication histories, previous
      surgeries, procedural details, and surgical complications, along with
      radiological interpretation of the HHs, were recorded. The primary outcome was
      seizure freedom, and secondary outcomes included medication reduction, seizure
      frequency, operative morbidity, and clinical outcome at the latest follow-up.
      RESULTS All 3 patients in the multi-institutional database had developed gelastic
      seizures related to HH at the ages of 7, 7, and 9 years. They presented for
      further treatment at 25, 28, and 48 years of age, after previous treatments with
      stereotactic radiosurgery in all cases and partial hamartoma resection in one
      case. One ablation was complicated by a small tract hemorrhage, which was stable
      on postoperative imaging. One patient developed hyponatremia and experienced
      weight gain, which were respectively managed with fluid restriction and
      counseling. At the most recent follow-up at a mean of 21 months (range 1-32
      months), one patient was seizure free while another had meaningful seizure
      reduction. Medication was reduced in one case. CONCLUSIONS Adults with gelastic
      seizures despite previous treatments can undergo MRg-LITT with reasonable safety
      and efficacy. This novel therapy may provide a minimally invasive alternative for
      primary and recurrent HH as the technique is refined.

PMID- 27690652
TI  - Utilizing personalized stereotactic frames for laser interstitial thermal
      ablation of posterior fossa and mesiotemporal brain lesions: a single-institution
      series.
AB  - OBJECTIVE The precision of laser probe insertion for interstitial thermal therapy
      of deep-seated lesions is limited by the method of stereotactic guidance. The
      objective of this study was to evaluate the feasibility of customized STarFix 3D
      printed stereotactic platforms to guide laser probe insertion into mesiotemporal
      and posterior fossa targets. METHODS The authors conducted a retrospective review
      of 5 patients (12-55 years of age) treated with laser interstitial thermal
      therapy (LITT) in which STarFix platforms were used for probe insertion. Bone
      fiducials were implanted in each patient's skull, and subsequent CT scans were
      used to guide the design of each platform and incorporate desired treatment
      trajectories. Once generated, the platforms were mounted on the patients'
      craniums and used to position the laser probe during surgery. Placement of the
      laser probe and the LITT procedure were monitored with intraoperative MRI.
      Perioperative and follow-up MRI were performed to identify and monitor changes in
      target lesions. RESULTS Accurate placement of the laser probe was observed in all
      cases. For all patients, thermal ablation was accomplished without intraoperative
      complications. Of the 4 patients with symptomatic lesions, 2 experienced complete
      resolution of symptoms, and 1 reported improved symptoms compared with baseline.
      CONCLUSIONS Customized stereotactic platforms were seamlessly incorporated into
      the authors' previously established LITT workflow and allowed for accurate
      treatment delivery.

PMID- 27690653
TI  - Thermal injury to corticospinal tracts and postoperative motor deficits after
      laser interstitial thermal therapy.
AB  - OBJECTIVE Laser interstitial thermal therapy (LITT) has been increasingly used to
      treat deep-seated tumors. Despite its being minimally invasive, there is a risk
      of LITT damaging adjacent critical structures, including corticospinal tracts
      (CSTs). In this study, the authors investigated the predictive value of overlap
      between the hyperthermic field and CSTs in determining postoperative motor
      deficit (PMDs). METHODS More than 140 patients underwent an LITT procedure in our
      institution between April 2011 and June 2015. Because of the tumor's proximity to
      critical structures, 80 of them underwent preoperative diffusion tensor imaging
      and were included in this study. Extent of the hyperthermic field was delineated
      by the software as thermal-damage-threshold (TDT) lines (yellow [43 degrees C for
      2 minutes], blue [43 degrees C for 10 minutes], and white [43 degrees C for 60
      minutes]). The maximum volume and the surface area of overlaps between motor
      fibers and the TDT lines were calculated and compared with the PMDs. RESULTS High
      grade glioma (n = 46) was the most common indication for LITT. Postoperative
      motor deficits (partial or complete) were seen in 14 patients (11 with permanent
      and 3 with temporary PMDs). The median overlap volumes between CSTs with yellow,
      blue, and white TDT lines in patients with any PMD (temporary or permanent) were
      1.15, 0.68, and 0.41 cm3, respectively. The overlap volumes and surface areas
      revealed significant differences in those with PMDs and those with no deficits (p
      = 0.0019 and 0.003, 0.012 and 0.0012, and 0.001 and 0.005 for the yellow, blue,
      and white TDT lines, respectively). The receiver operating characteristic was
      used to select the optimal cutoff point of the overlapped volumes and areas.
      Cutoff points for overlap volumes and areas based on optimal sensitivity (92%
      100%) and specificity (80%-90%) were 0.103, 0.068, and 0.046 cm3 and 0.15, 0.07,
      and 0.11 mm2 for the yellow, blue, and white TDT lines, respectively. CONCLUSIONS
      Even a minimal overlap between the TDT lines and CSTs can cause a PMD after LITT.
      Precise planning and avoidance of critical structures and important white matter
      fibers should be considered when treating deep-seated tumors.

PMID- 27690654
TI  - Stereotactic laser ablation as treatment for brain metastases that recur after
      stereotactic radiosurgery: a multiinstitutional experience.
AB  - OBJECTIVE Therapeutic options for brain metastases (BMs) that recur after
      stereotactic radiosurgery (SRS) remain limited. METHODS The authors provide the
      collective experience of 4 institutions where treatment of BMs that recurred
      after SRS was performed with stereotactic laser ablation (SLA). RESULTS Twenty
      six BMs (in 23 patients) that recurred after SRS were treated with SLA (2
      patients each underwent 2 SLAs for separate lesions, and a third underwent 2
      serial SLAs for discrete BMs). Histological findings in the BMs treated included
      the following: breast (n = 6); lung (n = 6); melanoma (n = 5); colon (n = 2);
      ovarian (n = 1); bladder (n = 1); esophageal (n = 1); and sarcoma (n = 1). With a
      median follow-up duration of 141 days (range 64-794 days), 9 of the SLA-treated
      BMs progressed despite treatment (35%). All cases of progression occurred in BMs
      in which < 80% ablation was achieved, whereas no disease progression was observed
      in BMs in which >= 80% ablation was achieved. Five BMs were treated with SLA,
      followed 1 month later by adjuvant SRS (5 Gy daily * 5 days). No disease
      progression was observed in these patients despite ablation efficiency of < 80%,
      suggesting that adjuvant hypofractionated SRS enhances the efficacy of SLA. Of
      the 23 SLA-treated patients, 3 suffered transient hemiparesis (13%), 1 developed
      hydrocephalus requiring temporary ventricular drainage (4%), and 1 patient who
      underwent SLA of a 28.9-cm3 lesion suffered a neurological deficit requiring an
      emergency hemicraniectomy (4%). Although there is significant heterogeneity in
      corticosteroid treatment post-SLA, most patients underwent a 2-week taper.
      CONCLUSIONS Stereotactic laser ablation is an effective treatment option for BMs
      in which SRS fails. Ablation of >= 80% of BMs is associated with decreased risk
      of disease progression. The efficacy of SLA in this setting may be augmented by
      adjuvant hypofractionated SRS.

PMID- 27690655
TI  - Percutaneous surgery for treatment of epidural spinal cord compression and spinal
      instability: technical note.
AB  - OBJECTIVE An emerging paradigm for treating patients with epidural spinal cord
      compression (ESCC) caused by metastatic tumors is surgical decompression and
      stabilization, followed by stereotactic radiosurgery. In the setting of rapid
      progressive disease, interruption or delay in return to systemic treatment can
      lead to a negative impact in overall survival. To overcome this limitation, the
      authors introduce the use of spinal laser interstitial thermotherapy (sLITT) in
      association with percutaneous spinal stabilization to facilitate a rapid return
      to oncological treatment. METHODS The authors retrospectively reviewed a
      consecutive series of patients with ESCC and spinal instability who were
      considered to be poor surgical candidates and instead were treated with sLITT and
      percutaneous spinal stabilization. Demographic data, Spine Instability Neoplastic
      Scale score, degree of epidural compression before and after the procedure,
      length of hospital stay, and time to return to oncological treatment were
      analyzed. RESULTS Eight patients were treated with thermal ablation and
      percutaneous spinal stabilization. The primary tumors included melanoma (n = 3),
      lung (n = 3), thyroid (n = 1), and renal cell carcinoma (n = 1). The median
      Karnofsky Performance Scale score before and after the procedure was 60, and the
      median hospital stay was 5 days (range 3-18 days). The median Spine Instability
      Neoplastic Scale score was 13 (range 12-16). The mean modified postoperative ESCC
      score (2.75 +/- 0.37) was significantly lower than the preoperative score (4.5 +/
      0.27) (Mann-Whitney test, p = 0.0044). The median time to return to oncological
      treatment was 5 days (range 3-10 days). CONCLUSIONS The authors present the first
      cohort of sLITT associated with a percutaneous spinal stabilization for the
      treatment of ESCC and spinal instability. This minimally invasive technique can
      allow a faster recovery without prejudice of adjuvant systemic treatment, with
      adequate local control and spinal stabilization.

PMID- 27690656
TI  - Stereotactic laser ablation for hypothalamic and deep intraventricular lesions.
AB  - OBJECTIVE Laser ablation is a novel, minimally invasive procedure that utilizes
      MRI-guided thermal energy to treat epileptogenic and other brain lesions. In
      addition to treatment of mesial temporal lobe epilepsy, laser ablation is
      increasingly being used to target deep or inoperable lesions, including
      hypothalamic hamartoma (HH), subependymal giant cell astrocytoma (SEGA), and
      exophytic intrinsic hypothalamic/third ventricular tumors. The authors reviewed
      their early institutional experience with these patients to characterize clinical
      outcomes in patients undergoing this procedure. METHODS A retrospective cohort (n
      = 12) of patients undergoing laser ablation at a single institution was
      identified, and clinical and radiographic records were reviewed. RESULTS Laser
      ablation was successfully performed in all patients. No permanent neurological or
      endocrine complications occurred; 2 (17%) patients developed acute obstructive
      hydrocephalus or shunt malfunction following treatment. Laser ablation of HH
      resulted in seizure freedom (Engel Class I) in 67%, with the remaining patients
      having a clinically significant reduction in seizure frequency of greater than
      90% compared with preoperative baseline (Engel Class IIB). Treatment of SEGAs
      resulted in durable clinical and radiographic tumor control in 2 of 3 cases, with
      one patient receiving adjuvant everolimus and the other receiving no additional
      therapy. Palliative ablation of hypothalamic/third ventricular tumors resulted in
      partial tumor control in 1 of 3 patients. CONCLUSIONS Early experience suggests
      that laser ablation is a generally safe, durable, and effective treatment for
      patients harboring HHs. It also appears effective for local control of SEGAs,
      especially in combination therapy with everolimus. Its use as a palliative
      treatment for intrinsic hypothalamic/deep intraventricular tumors was less
      successful and associated with a higher risk of serious complications. Additional
      experience and long-term follow-up will be beneficial in further characterizing
      the effectiveness and risk profile of laser ablation in treating these lesions in
      comparison with conventional resective surgery or stereotactic radiosurgery.

PMID- 27690657
TI  - Laser interstitial thermal therapy for newly diagnosed and recurrent
      glioblastoma.
AB  - OBJECTIVE Glioblastoma (GBM) is the most common and deadly malignant primary
      brain tumor. Better surgical therapies are needed for newly diagnosed GBMs that
      are difficult to resect and for GBMs that recur despite standard therapies. The
      authors reviewed their institutional experience of using laser interstitial
      thermal therapy (LITT) for the treatment of newly diagnosed or recurrent GBMs.
      METHODS This study reports on the pre-LITT characteristics and post-LITT outcomes
      of 8 patients with newly diagnosed GBMs and 13 patients with recurrent GBM who
      underwent LITT. RESULTS Compared with the group with recurrent GBMs, the patients
      with newly diagnosed GBMs who underwent LITT tended to be older (60.8 vs 48.9
      years), harbored larger tumors (22.4 vs 14.6 cm3), and a greater proportion had
      IDH wild-type GBMs. In the newly diagnosed GBM group, the median progression-free
      survival and the median survival after the procedure were 2 months and 8 months,
      respectively, and no patient demonstrated radiographic shrinkage of the tumor on
      follow-up imaging. In the 13 patients with recurrent GBM, 5 demonstrated a
      response to LITT, with radiographic shrinkage of the tumor following ablation.
      The median progression-free survival was 5 months, and the median survival was
      greater than 7 months. CONCLUSIONS In carefully selected patients with recurrent
      GBM, LITT may be an effective alternative to surgery as a salvage treatment. Its
      role in the treatment of newly diagnosed unresectable GBMs is not established yet
      and requires further study.

PMID- 27690658
TI  - Laser interstitial thermal therapy followed by minimal-access transsulcal
      resection for the treatment of large and difficult to access brain tumors.
AB  - OBJECTIVE Laser interstitial thermal therapy (LITT), sometimes referred to as
      "stereotactic laser ablation," has demonstrated utility in a subset of high-risk
      surgical patients with difficult to access (DTA) intracranial neoplasms. However,
      the treatment of tumors larger than 10 cm3 is associated with suboptimal outcomes
      and morbidity. This may limit the utility of LITT in dealing with precisely those
      large or deep tumors that are most difficult to treat with conventional
      approaches. Recently, several groups have reported on minimally invasive
      transsulcal approaches utilizing tubular retracting systems. However, these
      approaches have been primarily used for intraventricular or paraventricular
      lesions, and subtotal resections have been reported for intraparenchymal lesions.
      Here, the authors describe a combined approach of LITT followed by minimally
      invasive transsulcal resection for large and DTA tumors. METHODS The authors
      retrospectively reviewed the results of LITT immediately followed by minimally
      invasive, transsulcal, transportal resection in 10 consecutive patients with
      unilateral, DTA malignant tumors > 10 cm3. The patients, 5 males and 5 females,
      had a median age of 65 years. Eight patients had glioblastoma multiforme (GBM), 1
      had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain
      metastasis. The median tumor volume treated was 38.0 cm3. RESULTS The median
      tumor volume treated to the yellow thermal dose threshold (TDT) line was 83%
      (range 76%-92%), the median tumor volume treated to the blue TDT line was 73%
      (range 60%-87%), and the median extent of resection was 93% (range 84%-100%). Two
      patients suffered mild postoperative neurological deficits, one transiently. Four
      patients have died since this analysis and 6 remain alive. Median progression
      free survival was 280 days, and median overall survival was 482 days. CONCLUSIONS
      Laser interstitial thermal therapy followed by minimally invasive transsulcal
      resection, reported here for the first time, is a novel option for patients with
      large, DTA, malignant brain neoplasms. There were no unexpected neurological
      complications in this series, and operative characteristics improved as surgeon
      experience increased. Further studies are needed to elucidate any differences in
      survival or quality of life metrics.

PMID- 27690660
TI  - Stereotactic robot-assisted MRI-guided laser thermal ablation of radiation
      necrosis in the posterior cranial fossa: technical note.
AB  - Laser interstitial thermal therapy (LITT) is a minimally invasive procedure used
      to treat a variety of intracranial lesions. Utilization of robotic assistance
      with stereotactic procedures has gained attention due to potential for advantages
      over conventional techniques. The authors report the first case in which robot
      assisted MRI-guided LITT was used to treat radiation necrosis in the posterior
      fossa, specifically within the cerebellar peduncle. The use of a stereotactic
      robot allowed the surgeon to perform LITT using a trajectory that would be
      extremely difficult with conventional arc-based techniques. A 60-year-old man
      presented with facial weakness and brainstem symptoms consistent with radiation
      necrosis. He had a history of anaplastic astrocytoma that was treated with
      CyberKnife radiosurgery 1 year prior to presentation, and he did well for 11
      months until his symptoms recurred. The location and form of the lesion precluded
      excision but made the patient a suitable candidate for LITT. The location and
      configuration of the lesion required a trajectory for LITT that was too low for
      arc-based stereotactic navigation, and thus the ROSA robot (Medtech) was used.
      Using preoperative MRI acquisitions, the lesion in the posterior fossa was
      targeted. Bone fiducials were used to improve accuracy in registration, and the
      authors obtained an intraoperative CT image that was then fused with the MR image
      by the ROSA robot. They placed the laser applicator and then ablated the lesion
      under real-time MR thermometry. There were no complications, and the patient
      tolerated the procedure well. Postoperative 2-month MRI showed complete
      resolution of the lesion, and the patient had some improvement in symptoms.

PMID- 27690659
TI  - Intracerebral laser interstitial thermal therapy followed by tumor resection to
      minimize cerebral edema.
AB  - OBJECTIVE Laser interstitial thermal therapy (LITT) is used in numerous
      neurosurgical applications including lesions that are difficult to resect. Its
      rising popularity can be attributed to its minimally invasive approach, improved
      accuracy with real-time MRI guidance and thermography, and enhanced control of
      the laser. One of its drawbacks is the possible development of significant edema,
      which contributes to extended hospital stays and often necessitates hyperosmolar
      or steroid therapy. Here, the authors discuss the use of minimally invasive
      craniotomy to resect tissue ablated with LITT in attempt to minimize cerebral
      edema. METHODS Five patients with glioblastoma multiforme prospectively underwent
      LITT followed by resection. The LITT was performed with the aid of an MR
      compatible skull-mounted frame in the MRI suite. Ablated tumor was then resected
      via small craniotomy by using the NICO Myriad system or cavitron ultrasonic
      surgical aspirator. Postoperative management involved dexamethasone
      administration slowly tapered over several weeks. RESULTS The use of resection
      following LITT, as compared with open resection or LITT alone, did not extend the
      hospital stay except in 1 patient who required 3-day inpatient management of
      edema with a trapped ventricle. No new neurological deficits were encountered,
      although 1 patient developed seizures postoperatively. No increase in infection
      rates was identified. CONCLUSIONS Resection of ablated tumor is a viable option
      to reduce the incidence of neurological deficits due to edema following LITT.
      This approach appears to mitigate cerebral edema by increasing available volume
      for mass effect and reducing the tissue burden that may promote an inflammatory
      response.

PMID- 27690661
TI  - Putting the Fear Back Again (and Within Individuals): Revisiting the Role of Fear
      in Persuasion.
AB  - The overwhelming majority of fear appeal research came from the between
      individuals approach and yielded consistent evidence for a linear fear-persuasion
      relationship. A recent review suggested that the within-individuals approach
      might be more appropriate. Studies that measured fear at multiple time points
      have consistently revealed a curvilinear association between fear and persuasion
      predicted by the drive model. A Web-based experiment (N = 454) using tobacco
      warning labels was conducted to replicate the inverted-U shape curvilinear
      relationship between fear and persuasion, and to revisit the role of fear in fear
      appeal theories. Results showed that the inverted-U fear curve positively
      predicted persuasion and reduced maladaptive responses, and that the linear
      trajectory of fear positively predicted maladaptive responses and failure of
      persuasion.

PMID- 27690662
TI  - Titanium-nitride-oxide-coated coronary stents: insights from the available
      evidence.
AB  - Coating of stent surface with a biocompatible material is suggested to improve
      stent safety profile. A proprietary process was developed to coat titanium
      nitride-oxide on the stent surface, based on plasma technology that uses the nano
      synthesis of gas and metal. Preclinical in vitro and in vivo investigation
      confirmed blood compatibility of titanium (nitride-) oxide films. Titanium
      nitride-oxide-coated stents demonstrated a better angiographic outcome, compared
      with bare-metal stents at mid-term follow-up; however, they failed to achieve non
      inferiority for angiographic outcome versus second-generation drug-eluting
      stents. Observational studies showed adequate clinical outcome at mid-term follow
      up. Non-randomized studies showed an outcome of titanium-nitride-oxide-coated
      stents comparable to - or better than - first-generation drug-eluting stents at
      long-term follow-up. Two randomized controlled trials demonstrated comparable
      efficacy outcome, and a better safety outcome of titanium-nitride-oxide-coated
      stents versus drug-eluting stents at long-term follow-up. Evaluation by optical
      coherence tomography at mid-term follow-up revealed better neointimal strut
      coverage associated with titanium-nitride-oxide-coated stents versus drug-eluting
      stents; yet, neointimal hyperplasia thickness was greater. Key messages Stents
      coated with titanium-nitride-oxide demonstrated biocompatibility in preclinical
      studies: they inhibit platelet and fibrin deposition, and reduce neointimal
      growth. In observational and non-randomized studies, titanium-nitride-oxide
      coated stents were associated with adequate safety and efficacy outcome. In
      randomized trials of patients with acute coronary syndrome, titanium-nitride
      oxide-coated stents were associated with a better safety outcome, compared with
      drug-eluting stents; efficacy outcome was comparable.

PMID- 27690663
TI  - Pharmacological treatment of children and adolescents with depression.
AB  - INTRODUCTION: Despite an increasing number of studies, there is debate whether
      antidepressants have a favorable benefit/risk balance in depressed youth. Areas
      covered: A systematic search identified 23 systematic reviews and meta-analyses
      published between 2010-2016. More than 30 controlled clinical trials were
      conducted in adolescents, but only a few in pre-pubertal patients. About one
      third of the trials were severely statistically underpowered. Most studies failed
      to detect differences from placebo, but a few found fluoxetine effective.
      Although no suicide occurred in these studies, antidepressants increased
      suicidality risk (including suicidal ideation and behavior) versus placebo (OR =
      2.39). Only two placebo-controlled trials with acceptable statistical power were
      publicly funded: both showed efficacy of fluoxetine, and one found a higher
      incidence of suicidality (OR = 3.7, 95% C.I. 1.00-13.7). Expert opinion: In
      youth, antidepressants have, on average, a small therapeutic effect. The high
      placebo response is exacerbated by the large number of sites in many industry
      funded studies. There is evidence that fluoxetine leads to greater and faster
      improvement than placebo or psychotherapy in adolescents. Considering both the
      high response to non-specific interventions and safety concerns, antidepressants
      should be used cautiously in youth, and limited to patients with moderate-to
      severe depression for whom psychosocial interventions are either ineffective or
      not feasible.

PMID- 27690664
TI  - Emerging growth factor receptor antagonists for the treatment of renal cell
      carcinoma.
AB  - INTRODUCTION: The landscape of systemic treatment for metastatic renal cell
      carcinoma (RCC) has dramatically changed with the introduction of targeted agents
      including vascular endothelial growth factor (VEGF) inhibitors. Recently,
      multiple new agents including growth factor receptor antagonists and a checkpoint
      inhibitor were approved for the treatment of refractory metastatic RCC based on
      encouraging benefit shown in clinical trials. Areas covered: The background and
      biological rationale of existing treatment options including a brief discussion
      of clinical trials which led to their approval, is presented. This is followed by
      reviewing the limitations of these therapeutic options, medical need to develop
      new treatments and major goals of ongoing research. We then discuss two recently
      approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and
      a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to
      drug development, and future directions in treatment of metastatic RCC. Expert
      opinion: Recently approved growth factor receptor antagonists have shown
      encouraging survival benefit but associated drug toxicity is a major issue.
      Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, has similarly shown
      survival benefit and is well tolerated. With multiple options now available in
      this patient population, the right sequence of these agents remains to be
      determined.

PMID- 27690665
TI  - Chemical JAK inhibitors for the treatment of rheumatoid arthritis.
AB  - INTRODUCTION: Considerable advances in the treatment of rheumatoid arthritis (RA)
      have been made following the advent of biological disease-modifying anti
      rheumatic drugs (DMARDs). However, biological DMARDs require intravenous or
      subcutaneous injection and some patients fail to respond to these drugs or lose
      their primary response. Currently, Janus kinase (JAK) inhibitors have been
      developed as a new class of DMARD that inhibits the non-receptor tyrosine kinase
      family JAK involved in intracellular signaling of various cytokines and growth
      factors. Area covered: Several JAK inhibitors such as tofacitinib and baricitinib
      are oral synthetic DMARD that inhibit JAK1, 2 and 3. Both drugs have shown
      feasible efficacy and tolerable safety. In this article, efficacy and adverse
      events from the phase III trials of JAK inhibitors are overviewed. In addition,
      pharmacokinetics and mechanism of action of JAK inhibitors in relevance to
      efficacy and adverse events are covered. Expert opinion: JAK inhibitors are novel
      therapies for RA that inhibit multiple cytokines and signaling pathways. Further
      studies are needed to determine their risk-benefit ratio and selection of the
      most appropriate patients for such therapy.

PMID- 27690666
TI  - Do oral contraceptives increase epileptic seizures?
AB  - INTRODUCTION: Hormonal contraceptives are used by over 100 million people
      worldwide. Recently, there has been an emerging interest in studying the
      potential impact of oral contraceptives (OCs) on certain neurological conditions.
      It has been suspected for some time that hormonal birth control increases seizure
      activity in women with epilepsy, but there is little supportive data. Areas
      covered: Literature from PubMed and online sources was analyzed with respect to
      hormonal contraception and epilepsy or seizures. New evidence indicates that OCs
      can cause an increase in seizures in women with epilepsy. The epilepsy birth
      control registry, which surveyed women with epilepsy, found that those using
      hormonal contraceptives self-reported 4.5 times more seizures than those that did
      not use such contraceptives. A preclinical study confirmed these outcomes wherein
      epileptic animals given ethinyl estradiol, the primary component of OCs, had more
      frequent seizures that are more likely to be resistant. Expert commentary: OC
      pills may increase seizures in women with epilepsy and such refractory seizures
      are more likely to cause neuronal damage in the brain. Thus, women of child
      bearing age with epilepsy should consider using non-hormonal forms of birth
      control to avoid risks from OC pills. Additional research into the mechanisms and
      prospective clinical investigation are needed.

PMID- 27690667
TI  - Pharmacodynamics, pharmacokinetics and clinical efficacy of phosphodiesterase-5
      inhibitors.
AB  - INTRODUCTION: Phosphodiesterase type 5 inhibitors (PDE5Is) are the first-line
      drugs in the management of erectile dysfunction (ED). However, over the past two
      decades tremendous efforts have been made to identify new clinical uses of PDE5Is
      beyond their roles in ED. Areas covered: Basic science articles, clinical trials,
      reviews, and meta-analysis published between 1996 and 2015 were searched using
      MEDLINE (PubMed interface) to collect the most relevant and impactful studies
      from our perspectives as practicing urologists. This review mainly focuses on the
      level one evidence-based clinical efficacy and drug-related toxicity of oral
      PDE5Is. In addition, drug discovery, pharmacokinetics and pharmacodynamics,
      potential use in other diseases, and future directions are discussed. Expert
      opinion: On-demand PED5Is for the treatment of ED has shifted toward chronic
      administration in a broad spectrum of conditions that are thought to be
      associated with endovascular health. Several studies have shown that PDE5Is may
      play a cardioprotective or neuroprotective role. Further studies are under way to
      verify beneficial effects of PDE5I in non-urological conditions.

PMID- 27690668
TI  - Are emerging PGD2 antagonists a promising therapy class for treating asthma?

PMID- 27690670
TI  - STARTING ARIPIPRAZOLE LONG-ACTING-ONCE-A-MONTH EARLY IN TREATMENT: WHY, HOW AND
      FOR WHOM? EXPERT CONSENSUS AND PRACTICAL RECOMMENDATIONS BY A PANEL OF ITALIAN
      CLINICIANS.
AB  - INTRODUCTION: Aripiprazole long acting once-monthly (AOM) is approved for the
      treatment of schizophrenia in adults. Despite recent evidence of AOM efficacy in
      the acute treatment of schizophrenia, it is recommended that AOM should be
      started once the acute symptoms are controlled and patients are stabilized.
      However, there currently are no definitive guidelines exactly describing when a
      patient is to be considered stabilized enough to start AOM and which the patients
      are for whom an early AOM start is to be preferred. AREAS COVERED: A panel of
      Italian clinicians experienced with real world use of AOM met to discuss the
      scenarios where an early (i.e., immediately after controlling the acute symptoms)
      start of AOM may be suggested. Real life clinical experiences were shared and a
      consensus was reached. EXPERT OPINION: There are cases when the risks/benefits
      ratio suggests to start AOM early, i.e. immediately after the acute symptoms have
      been stabilized, as opposed to starting it several days/weeks after the
      stabilization of acute symptoms. Clinical pearls, guidelines and opinions are
      provided.

PMID- 27690669
TI  - Ixekizumab for treatment of adults with moderate-to-severe plaque psoriasis and
      psoriatic arthritis.
AB  - INTRODUCTION: The interleukin (IL)-17 family of cytokines has emerged as an
      important pro-inflammatory mediator of psoriasis and psoriatic arthritis (PsA).
      Ixekizumab is an IL17A inhibitor that has been approved for the treatment of
      chronic plaque psoriasis. Phase III studies of ixekizumab in treating of PsA
      demonstrated promise by minimizing disease severity and progression. Areas
      covered: This review focuses on the biologic properties, pharmacokinetics and key
      clinical trial results that demonstrated the safety and efficacy of ixekizumab in
      treating psoriatic disease. Expert commentary: Ixekizumab is a biologic that has
      been approved for the treatment of chronic plaque psoriasis. With respect to
      safety, ixekizumab is generally well tolerated with injection-site reactions,
      nasopharyngitis, and upper respiratory tract infections being the most common
      adverse events. Most patients with anti-drug antibodies have low antibody titer
      levels resulting in no meaningful interference in clinical response to
      ixekizumab.

PMID- 27690671
TI  - Peptides as a therapeutic avenue for nanocarrier-aided targeting of glioma.
AB  - INTRODUCTION: Very few successful interventions have been possible in glioma
      therapy owing to its aggressive nature as well as its hindrance of targeted
      therapy together with the limited access afforded by the blood-brain barrier
      (BBB). With the advent of nanotechnology based delivery vehicles such as
      micelles, dendrimers, polymer-based nanoparticles and nanogels, the breach of the
      BBB has been facilitated. However, there remains the issue of targeted therapy
      for glioma cells. Peptide-mediated surface modification of nanocarriers serves
      this purpose, extending the ability to target glioma further than the enhanced
      permeability and retention effect. Areas covered: Here we have tried to re
      establish the significance of peptides that could be used in various ways for
      treating glioma. Peptide-embellished nanocarriers used to deliver anticancer
      drugs; nucleic acids (siRNA, miRNA); micelles or dendrimers grafted with
      immunogenic glioma-derived peptides used for stimulating active immunity in
      vaccine therapy, glioma targets for cell penetrating peptides and homing to
      specific receptors are reviewed. Expert opinion: Peptides have multifunctional
      potential in targeting, BBB and cell penetration, and can serve as antagonists of
      various ligands and agonists of particular over-expressed receptors as discussed
      in this review. Using peptides in targeted personalized therapy would be one step
      forward and may offer new avenues for glioma therapeutics.

PMID- 27690672
TI  - Myasthenia gravis: recent advances in immunopathology and therapy.
AB  - INTRODUCTION: Myasthenia gravis is the most frequent acquired disorder of
      neuromuscular transmission. In the majority of cases, pathogenic antibodies
      against components of the postsynaptic muscle endplate membrane can be detected.
      In recent years there have been significant advances in the pathophysiological
      understanding and therapy of the disease. Areas covered: PubMed searches were
      conducted for the term 'myasthenia gravis' cross-referenced with the terms
      'immunology', 'subgroups', 'antibody', 'ocular', 'thymoma', 'treatment' and
      'thymectomy'. Additionally, we summarized the current state of immunopathology
      and therapy. Expert commentary: Immunological research defined new target
      antigens at the postsynaptic neuromuscular junction which along with clinical
      features allow a refined definition of disease subgroups. Overall the prognosis
      of myasthenia gravis with best possible symptomatic, immunosuppressive and
      supportive treatment is good but new immunomodulatory treatment options are
      developed for patients who do not respond well to the first line therapy. For
      most patients individually adapted long-term drug therapy is needed.

PMID- 27690673
TI  - Systemic inflammatory immune signatures in a patient with CRB1 linked retinal
      dystrophy.
AB  - BACKGROUND: In this report we describe, for the first time, the activation of the
      peripheral immune compartment in a patient with a CRB1 linked retinal
      degenerative disease, masquerading as intermediate uveitis. METHODS: To monitor
      the immune system during systemic immunosuppressive treatment, given for the
      initial diagnosis of intermediate uveitis, blood samples were taken before and
      during therapy, for analysis of peripheral blood mononuclear cell-subsets and
      circulating immune mediators. RESULTS: The levels of various pro-inflammatory
      immune mediators (including MIF, TSLP, CCL2/MCP-1, CXCL9, CXCL10, IFN-beta, IL-6,
      IL-17, IL-21, IL-22, and IL-23) were elevated in serum at the first time point,
      and decreased under immunosuppressive treatment. In parallel, the frequency of
      activated (CD86+) CD1c+ myeloid dendritic cells in blood was proportional to the
      central foveal thickness measured by optical coherence tomography. CONCLUSIONS:
      These observations challenge the current view on the distinct pathophysiology of
      retinal degenerative and retinal inflammatory conditions in this patient.

PMID- 27690675
TI  - Adapting L-Cells to the Rescue!

PMID- 27690674
TI  - Loop recorders for syncope evaluation: what is the evidence?
AB  - INTRODUCTION: Implantable loop recorders (ILRs) have become an important pillar
      in the diagnostic work-up of patients with unexplained syncope. Areas covered:
      The modern ILR is minimally-invasive and provides an extended-duration of
      monitoring with high diagnostic yield. These insertable cardiac monitors (ICMs)
      enable prolonged monitoring that extends the opportunity for symptom-rhythm
      correlation from days-weeks to years, with associated incremental diagnostic
      yield. Over the years, observational studies and randomized trials have supported
      a unique role for ILRs in the assessment of recurrent or high-risk unexplained
      syncope. Furthermore, ILRs have been used in the elderly, in children, patients
      with overt heart disease, and patients with conduction block with varying
      success. The current guidelines recommend ILRs in the early phase of evaluation
      in recurrent syncope, and as part of the comprehensive evaluation of high-risk
      patients with syncope. Expert commentary: In this review, we discuss the evidence
      surrounding ILRs, including comparison studies with 'conventional' management and
      the external loop recorder.

PMID- 27690676
TI  - Differential Effects of Two Antialdosterone Agents on Glycemic Control.

PMID- 27690678
TI  - Targeted therapies: what they teach us about the pathogenesis of psoriasis and
      psoriatic arthritis.
AB  - INTRODUCTION: Biologic therapy has revolutionized treatment pathways in psoriatic
      joint and skin disease. It has also provided a useful tool with which
      pathological pathways of this condition may be explored. Areas covered: This
      review presents data on the clinical and biological effects of targeted therapy
      in psoriatic arthritis and psoriasis. Therapeutic agents covered include
      inhibitors of TNFalpha, inhibitors of the IL-23/IL-17 axis and inhibitors of
      intracellular small molecules involved in the transduction of the inflammatory
      signal. Trial data on clinical and imaging efficacy is reviewed in parallel with
      studies on biological effects at tissue level. Pathological insights gained from
      the use of these treatments are explored. Expert commentary: A close relationship
      exists between specific pathological types and clinical manifestations of
      psoriatic disease, including responses to treatment. Studying these relationships
      is likely to improve understanding of disease and enable rational selection of
      specific treatments for patients with specific pathotypes.

PMID- 27690679
TI  - Recent advances in the management of juvenile systemic sclerosis.
AB  - INTRODUCTION: Juvenile Systemic Sclerosis (JSSc) is one of the most severe multi
      systemic connective tissue conditions encountered in pediatric rheumatology. Due
      to its high morbidity and mortality rate, early diagnosis, proper assessment and
      effective treatment are crucial. Areas covered: In this review, we will focus on
      the recent advances on the classification and general management of JSSc based on
      the literature search and on the Authors' experience. Expert commentary:
      Classification criteria for the pediatric forms of systemic sclerosis, the new
      proposed assessment tools, such as the juvenile systemic sclerosis severity
      score, named J4S, and new techniques for the internal organs assessment, will
      facilitate both daily practice and research projects. Unfortunately, no known
      drugs seem to be effective in preventing the development of disease complications
      although a few treatments, undertaken according to experience in adults, have
      shown some effects in arresting the disease progression.

PMID- 27690680
TI  - Neratinib for the treatment of breast cancer.
AB  - INTRODUCTION: Neratinib is an orally available, pan-HER inhibitor with clinical
      activity in patients with HER2-amplified and HER2-mutated breast cancer. Areas
      Covered. A summary of publically available and relevant clinical data on
      neratinib. Expert Opinion. Neratinib (N) is clearly distinct from lapatinib (L),
      a difference based on its broad anti-HER effect, its covalent target binding and
      its toxicity profile. The main toxicity of neratinib is gastro-intestinal and is
      essentially limited to diarrhea. Although not directly compared with single agent
      lapatinib, skin toxicity is much less pronounced with N. The direct clinical
      comparison of N-capecitabine versus L-capecitabine is the subject of the ongoing
      NALA-trial. In patients with advanced disease, neratinib has clinically relevant
      activity in patients with trastuzumab(T)-pretreated and unpretreated disease. In
      patients having completed one year of adjuvant trastuzumab, an additional year of
      neratinib further reduces the risk of recurrence of invasive disease. The
      activity of neratinib in HER2-mutated advanced disease is subject of ongoing
      clinical trials but preclinical and early clinical results are promising.
      Neratinib is a usefull drug and a valuable addition to the different anti-HER2
      drugs avalaible for patients with HER2-overexpressing and HER2-mutated breast
      cancer.

PMID- 27690681
TI  - Magnetic silica nanocomposites for magnetic hyperthermia applications.
AB  - This paper summarizes nearly all magnetic silica nanocomposites that have been
      synthesized for biomedical applications and evaluated under alternating magnetic
      field (AMF) from the point of view of heat generation. The use of these
      nanocomposites as a drug delivery system for remote control of drug release via
      applying AMF is described. Different parameters that affect the magnetic
      properties and therefore affect the amount of generated heat and the fact that
      sometimes these parameters are in conflict with each other are discussed. This
      review article presents insight into the synthesis of nanocomposites with optimal
      characteristics and use of them in optimal conditions to achieve the optimal
      magnetic properties for magnetic hyperthermia.

PMID- 27690682
TI  - Impact of nitroglycerin and glucagon administration on selective common bile duct
      cannulation and prevention of post-ERCP pancreatitis.
AB  - OBJECTIVE: Easy common bile duct (CBD) cannulation is associated with low
      complication rate. This study aimed to investigate the potential impact of
      nitroglycerin and glucagon administration on selective CBD cannulation and
      prevention of post-ERCP pancreatitis. METHODS: A prospective single center,
      double-blind randomized study in which a total of 455 patients were randomly
      assigned to CBD cannulation by receiving 6 puffs (2.4 mg) sublingual
      nitroglycerin and glucagon 1 mg intravenously (n = 227, group A) or 6 puffs
      sterile water and 20 mg hyoscine-n-butyl bromide intravenously (n = 228, group
      B). After ERCP, patients were followed for the development of drugs' side-effects
      and post-ERCP complications. RESULTS: There were no statistically significant
      differences between the two groups regarding demographic data and ERCP findings.
      Success rate of selective CBetaD cannulation was 95.15% in group A versus 82.29%
      in group B (p < .001). Time required for CBD cannulation was 2.82 +/- 2.31 min in
      group A versus 4.27 +/- 3.84 min in group B (p = .021). Needle-knife papillotomy
      was used in 11 (4.85%) patients of group A and 39 (17.11%) patients of group B (p
      = .001). The frequency of post-ERCP pancreatitis was significantly lower in group
      A than in group B (3.08% versus 7.46%, p = .037). No difference was observed
      between the two groups with regard to the occurrence of post-procedure
      hemorrhage. There was no procedure-related mortality; no adverse event related to
      the combination regimen was observed. CONCLUSIONS: Combined nitroglycerin and
      glucagon administration achieves a high selective CBC cannulation rates with
      concomitant reduction of post-ERCP pancreatitis incidence. However, further
      relative large-scale studies are needed to confirm our findings before definite
      conclusions can be drawn (Clinical trial registration number: NT: 4321).

PMID- 27690683
TI  - Cytomegalovirus in hematopoietic stem cell transplant recipients - management of
      infection.
AB  - INTRODUCTION: Cytomegalovirus (CMV) still causes significant morbidity and
      mortality in patients given allogeneic hematopoietic stem cell transplantation
      (HSCT). Despite effective pharmacotherapy, potentially life-threatening CMV
      disease occurs nowadays in up to 10% of HSCT recipients; moreover, routinely used
      anti-CMV agents have been shown to be associated with morbidity. Areas covered:
      This review examines different issues related to diagnosis and management of CMV
      infection in HSCT recipients, paying particular attention to the monitoring of
      CMV-specific immune recovery, approaches of adoptive cell therapy and new
      antiviral drugs. Expert commentary: Despite advances in diagnostic tests and
      treatment, there is still room for refining management of CMV in HSCT recipients.
      Immunological monitoring should be associated in the future to virological
      monitoring. The safety profile and efficacy of new anti-CMV agents should be
      compared with that of standard-of-care drugs. Donor-derived, pathogen-specific T
      cells adoptively transferred after transplantation could contribute to reduce the
      impact of CMV infection on patient's outcome.

PMID- 27690684
TI  - Novel adipokines WISP1 and betatrophin in PCOS: relationship to AMH levels,
      atherogenic and metabolic profile.
AB  - OBJECTIVE: To determine the levels of WISP1 and betatrophin in normal weight and
      obese women with polycystic ovary syndrome (PCOS) and to assess their
      relationship with anti-Mullerian hormone (AMH) levels, atherogenic profile and
      metabolic parameters Methods: In this prospective cross-sectional study, the
      study group was composed of 49 normal weighed and 34 obese women with PCOS
      diagnosed based on the Rotterdam criteria; 36 normal weight and 26 obese age
      matched non-hyperandrogenemic women with regular menstrual cycle. Serum WISP1,
      betatrophin, homeostasis model assessment of insulin resistance (HOMA-IR) and AMH
      levels were evaluated. Univariate and multivariate analyses were performed
      between betatrophin, WISP1 levels and AMH levels, metabolic and atherogenic
      parameters. RESULTS: Serum WISP1 and betatrophin values were elevated in the PCOS
      group than in the control group. Moreover, serum WISP1 and betatrophin levels
      were higher in the obese PCOS subgroup than in normal weight and obese control
      subgroups. Multivariate analyses revealed that Body mass index, HOMA-IR, AMH
      independently and positively predicted WISP1 levels. Serum betatrophin level
      variability was explained by homocysteine, HOMA-IR and androstenedione levels.
      CONCLUSION: WISP1 and betatrophin may play a key role on the pathogenesis of
      PCOS.

PMID- 27690685
TI  - Transanal total mesorectal excision for rectal cancer: The journey towards a new
      technique and its current status.
AB  - INTRODUCTION: The surgical approach to total mesorectal excision (TME) for rectal
      cancer has undergone a substantial evolution with the adoption of more minimally
      invasive procedures. Transanal TME (taTME) is the latest advanced technique
      pioneered to tackle difficult pelvic dissections. Areas covered: The evolution of
      TME surgery from open to laparoscopic, robotic and transanal techniques was
      explored in this review. The outcomes to date on the latest approach, taTME, are
      reviewed and the future direction of rectal cancer surgery proposed. A literature
      search was performed using Embase, Medline, Web of Science and Cochrane databases
      for articles published between January 2005 to May 2016 using the keywords
      "transanal", "TME", "laparoscopy", "robotics", "minimally invasive", "outcomes"
      and "training". Expert Commentary: Surgical experience in taTME is growing and
      randomised controlled trials have been planned and initiated worldwide. However,
      the learning curve for this procedure remains to be established and a structured
      training programme is necessary to ensure safe introduction and dissemination of
      the technique in the clinical setting. Further innovation including stereotactic
      navigation and more specialised transanal equipment are currently being explored
      and are likely to enhance the technique further.

PMID- 27690686
TI  - Vaccines for piscirickettsiosis (salmonid rickettsial septicaemia, SRS): the
      Chile perspective.
AB  - INTRODUCTION: Piscirickettsia salmonis (P. salmonis) is the aetiological
      bacterium of the contagious disease piscirickettsiosis or salmonid rickettsial
      septicaemia (SRS) and causes significant economic losses to aquaculture
      production in Chile. Current strategies to control infection are i)
      indiscriminate antibiotic use and ii) vaccination with predominantly P. salmonis
      bacterin vaccines that do not provide acceptable levels of protection against
      piscirickettsiosis. Areas covered: This review covers the basic biology of P.
      salmonis, clinical piscirickettsiosis and disease control, the development of
      current P. salmonis vaccines, innate and adaptive immunity and a 5-year plan to
      develop new piscirickettsiosis vaccines. Expert commentary: Fundamental knowledge
      is lacking on the complexities of P. salmonis-host interactions, relating to
      bacterial virulence and host innate and adaptive immune responses, which needs to
      be addressed. The development of new P. salmonis vaccines needs the application
      of comprehensive 'omics' technologies to identify candidate vaccine antigens
      capable of stimulating long-lasting protective immune responses.

PMID- 27690687
TI  - A comparison between the effects of metformin and megestrol on simple endometrial
      hyperplasia.
AB  - INTRODUCTION: Endometrial hyperplasia is one of the most serious causes of severe
      abnormal bleeding and also can be a precursor of endometrial carcinoma.
      OBJECTIVE: The purpose of the present study was to compare the effects of
      metformin and megestrol on the endometrial hyperplasia. METHODS: The study was
      performed as a randomized clinical trial on 42 cases of histopathologically
      confirmed simple endometrial hyperplasia without atypia. The eligible women were
      randomly assigned into two groups. In metformin group, metformin was prescribed,
      500 mg twice a day (1000 mg daily), for a duration of 4 weeks, and then, followed
      by 1500 mg daily, for 8 more weeks. In the megestrol group, megestrol was
      prescribed 40 mg daily for 12 weeks. At the end of the duration of the treatment,
      endometrial sampling was performed and the results were compared between the two
      groups. RESULTS: The women of the two groups did not have significant difference
      according to age, BMI and gravidity, parity and history of abortion. Overall, 18
      women (81.8%) in metformin group and 12 women (60%) in the megestrol group had
      normal endometrial histology, after 12 weeks of treatment (p = 0.11). CONCLUSION:
      Metformin is comparable with megestrol for the treatment of simple endometrial
      hyperplasia.

PMID- 27690689
TI  - Ceftobiprole medocaril (BAL-5788) for the treatment of complicated skin
      infections.
AB  - INTRODUCTION: With resistance of S. aureus, the most prevalent identified
      pathogen in skin and soft tissue infections, on the rise, the need for safe,
      effective, and well-tolerated antibiotics is crucial. Ceftobiprole medocaril (BAL
      5788), ceftobiprole's parenteral prodrug, is a bactericidal cephalosporin with
      broad Gram-positive and Gram-negative activity that has shown to be well
      tolerated and noninferior to vancomycin and vancomycin plus ceftazidime in the
      treatment of MRSA complicated skin and skin structure infections (cSSSIs) in
      clinical trials. Areas Covered: This article overviews ceftobiprole medocaril's
      use for cSSSI, with specific focus on clinical efficacy and safety data in
      addition to summary information on its basic chemistry, microbiological profile,
      and pharmacokinetic/pharmacodynamic relationships supporting its use in cSSSIs.
      Information sources include peer-reviewed scientific literature, conference
      proceedings, publically available regulatory reports, as well as information from
      the drug sponsor's website. Expert Commentary: With increasing antibiotic
      resistance, safe, effective antibiotics agents are a welcome sight. There has
      been clinical evidence in support of using ceftobiprole for treatment of Gram
      positive and -negative infections, including MRSA and susceptible P. aeruginosa.
      This broad antimicrobial activity might allow ceftobiprole to be an alternative
      to dual therapy combinations when potential drug toxicities, drug-drug or drug
      disease interactions are concerns for other agents.

PMID- 27690688
TI  - Infections caused by Mycobacterium abscessus: epidemiology, diagnostic tools and
      treatment.
AB  - INTRODUCTION: Mycobacterium abscessus is an emerging mycobacteria that is
      responsible for lung diseases and healthcare-associated extrapulmonary
      infections. Recent findings support its taxonomic status as a single species
      comprising 3 subspecies designated abscessus, bolletii and massiliense. We
      performed a review of English-language publications investigating all three of
      these subspecies. Areas covered: Worldwide, human infections are often
      attributable to environmental contamination, although the isolation of M.
      abscessus in this reservoir is very rare. Basic research has demonstrated an
      association between virulence and cell wall components and cording, and genome
      analysis has identified gene transfer from other bacteria. The bacteriological
      diagnosis of M. abscessus is based on innovative tools combining molecular
      biology and mass spectrometry. Genotypic and phenotypic susceptibility testing
      are required to predict the success of macrolide (clarithromycin or azithromycin)
      based therapeutic regimens. Genotyping methods are helpful to assess relapse and
      cross-transmission and to search for a common source. Treatment is not
      standardised, and outcomes are often unsatisfactory. Expert commentary: M.
      abscessus is still an open field in terms of clinical and bacteriological
      research. Further knowledge of its ecology and transmission routes, as well as
      host-pathogen interactions, is required. Because the number of human cases is
      increasing, it is also necessary to identify more active treatments and perform
      clinical trials to assess standard effective regimens.

PMID- 27690690
TI  - Dissociation of Molecular and Endocrine Circadian Rhythms in Male Mice Lacking
      Bmal1 in the Adrenal Cortex.
AB  - The circadian rhythm of glucocorticoids affects diverse physiological systems,
      including stress responses and the coordination of rhythmic functions in
      peripheral and central tissues. Circadian clocks are considered to be important
      coordinators of glucocorticoid release and loss of the core clock component Brain
      and muscle Arnt-like protein-1 leads to ablation of behavioral and physiological
      rhythms, hypocortisolism, impaired ACTH, and behavioral stress responses.
      Transplantation and conditional clock gene knock-down studies in mice suggest an
      important role of local adrenocortical clock function in this context. Here, we
      present a Cre-loxP-mediated conditional knockout of Bmal1 in the steroidogenic
      cells of the adrenal cortex in mice. Mutant animals show a loss of molecular
      clock gene activity rhythms in this tissue with subsequent disruption of rhythmic
      steroidogenic gene expression. However, despite this loss of normal clock
      rhythmicity in the adrenal cortex, behavioral and physiological rhythms and acute
      stress responses persist in mutant mice. These findings reveal a dissociation of
      transcriptional and endocrine rhythm regulation in the adrenal cortex, arguing
      for a less pivotal function of the local clock machinery in the regulation of
      circadian and acute glucocorticoid outputs.

PMID- 27690691
TI  - Induction of Amnion Epithelial Apoptosis by Cortisol via tPA/Plasmin System.
AB  - Rupture of fetal membranes (ROM) can initiate parturition at both term and
      preterm birth. Apoptosis of the amnion epithelium plays a key role in structural
      remodeling of the membranes preceding ROM. However, the causative factors for
      apoptosis remain unidentified. Toward the end of gestation, a feed-forward
      regeneration of cortisol via 11beta-hydroxysteroid dehydrogenase 1 exists in the
      fetal membranes. Here, we have examined whether cortisol accumulation is a
      causative factor for amnion cells apoptosis. By using primary human amnion
      epithelial and fibroblast cells, we demonstrated cortisol induced apoptosis
      specifically in epithelial cells but not in fibroblasts via reciprocal regulation
      of tissue-type plasminogen activator (tPA)/plasmin system. Cortisol increased
      PLAT expression, the gene encoding tPA, via glucocorticoid receptor binding to a
      glucocorticoid response element in PLAT promoter, thereby increasing plasmin
      activity in epithelial cells. Further study revealed that a Fas-mediated
      extrinsic apoptotic pathway was involved in the induction of epithelial cells
      apoptosis by cortisol, which was blocked by inhibiting either tPA or plasmin.
      Consistently, cortisol increased cleaved-caspase-3 and tPA abundance in amnion
      tissue explants. Moreover, the abundance of cortisol, cleaved-caspase-3, and tPA
      was significantly increased in amnion tissue after labor-initiated spontaneous
      rupture of membranes. In conclusion, local accumulation of cortisol is a
      causative factor for amnion epithelial apoptosis via activation of tPA/plasmin
      system toward the end of gestation. This may contribute to the ROM at both term
      and preterm birth.

PMID- 27690692
TI  - FGF21-FGFR1 Coordinates Phospholipid Homeostasis, Lipid Droplet Function, and ER
      Stress in Obesity.
AB  - The antiobese and antidiabetic fibroblast growth factor 21 (FGF21) regulates
      lipid metabolism and energy homeostasis by targeting the betaKlotho-FGFR1
      (fibroblast growth factor receptor 1) binary complex in adipose tissue
      adipocytes. Because lipid droplet is the organelle responsible for storing lipid
      energy in adipocytes, it is the plausible target of FGF21 action. However, the
      impact of the FGF21-betaKlotho-FGFR1 signaling pathway on the functions of the
      lipid droplet is not clearly understood. Using our mouse models of adipocyte
      specific FGFR1 ablation and hepatic overexpression of FGF21 with diet-induced
      obesity established previously, we analyzed the alterations of the pathways
      involved in energy and substrate metabolism that is attributable to the dynamic
      functions of the lipid droplet. In addition to the previous reports showing that
      FGFR1 deficiency abrogated lipolysis, fatty acid oxidation, and energy
      expenditure promoted by the elevated FGF21 signal, we observed that the
      deficiency up-regulated the biosynthesis and remodeling of membrane phospholipids
      that are important for the biogenesis and expansion of the droplet, whereas the
      enhanced FGF21 signal constrained the biosynthesis of phospholipids. As a result,
      the loss of adipose FGFR1 led to a sustained droplet expansion and endoplasmic
      reticulum (ER) stress, whereas the enhanced FGF21 signal suppressed them in
      obesogenesis. These new findings reveal that the FGF21-betaKlotho-FGFR1 signaling
      axis plays roles in maintaining phospholipid homeostasis and the dynamic
      functions of the lipid droplet, whereas protecting against ER stress, and suggest
      a potential link of phospholipid biosynthesis, lipid droplet dynamics, ER stress,
      and energy homeostasis in adipose tissue coordinated by this signaling axis.

PMID- 27690693
TI  - Applicability of the Proposed Japanese Model for the Classification of Gastric
      Cancer Location: The "PROTRADIST" Retrospective Study.
AB  - BACKGROUND: The extension of lymphadenectomy for surgical treatment of gastric
      cancer remains discordant among European and Japanese surgeons. Kinami et al.
      (Kinami S, Fujimura T, Ojima E, et al. PTD classification: proposal for a new
      classification of gastric cancer location based on physiological lymphatic flow.
      Int. J. Clin. Oncol. 2008;13:320-329) proposed a new experimental classification,
      the "Proximal zone, Transitional zone, Distal zone" (PTD) classification, based
      on the physiological lymphatic flow of gastric cancer site. The aim of the
      present retrospective study is to assess the applicability of PTD Japanese model
      in gastric cancer patients of our Western surgical department. METHODS: Two
      groups of patients with histologically documented adenocarcinoma of the stomach
      were retrospectively obtained: In the first group were categorized 89 patients
      with T1a-T1b tumor invasion; and in the second group were 157 patients with T2-T3
      category. The data collected were then categorized according to the PTD
      classification. RESULTS: In the T1a-T1b group there were no lymph node metastases
      within the r-GA or r-GEA compartments for tumors located in the P portion, and
      similarly there were no lymphatic metastases within the l-GEA or p-GA
      compartments for tumors located in the D portion. On the contrary, in the T2-T3
      group the lymph node metastases presented a diffused spreading with no
      statistical significance between the two classification models. CONCLUSIONS: Our
      results show that the PTD classification based on physiological lymphatic flow of
      the gastric cancer site is a more physiological and clinical version than the
      Upper, Medium And Lower classification. It represents a valuable and applicable
      model of cancer location that could be a guide to a tailored surgical approach in
      Italian patients with neoplasm confined to submucosa. Nevertheless, in order to
      confirm our findings, larger and prospective studies are needed.

PMID- 27690694
TI  - Complications of invasive mycoses in organ transplant recipients.
AB  - INTRODUCTION: Opportunistic mycoses remain a significant complication in organ
      recipients. Areas covered: This review is an evidence-based presentation of
      current state-of-knowledge and our perspective on recent developments in the
      field Expert commentary: Invasive fungal infections are associated with reduced
      allograft and patient survival, increase in healthcare resource utilization, and
      newly appreciated but largely unrecognized immunologic sequelae, such as immune
      reconstitution syndrome. Given adverse outcomes associated with established
      infections, prophylaxis is a widely used strategy for the prevention of these
      infections. Currently available biomarkers that detect circulating fungal cell
      wall constituents i.e., galactomannan and 1, 3-beta-D-glucan have not proven to
      be beneficial as screening tools for employing targeted prophylaxis or as
      diagnostic assays in this patient population. However, subsets of patients at
      risk for opportunistic fungal infections can be identified based on clinically
      identifiable characteristics or events. Preventive strategies targeted towards
      these patients are a rational approach for optimizing outcomes.

PMID- 27690695
TI  - Placental leptin mRNA expression and serum leptin levels in pre-eclampsia
      associated with HIV infection.
AB  - Leptin, primarily produced by adipocytes, is implicated in the development of pre
      eclampsia. This study examines placental leptin production and serum leptin
      levels in HIV infected and uninfected normotensive and pre-eclamptic pregnancies.
      Placental leptin production was analysed by RT-PCR and serum leptin levels by
      ELISA in normotensive (n = 90) and pre-eclamptic (n = 90) pregnancies which were
      further stratified by HIV status. Placental leptin production was higher in pre
      eclampsia compared to normotensive pregnancies irrespective of HIV status (p =
      .04). Serum leptin was non-significantly raised in HIV uninfected (p = .42) but
      lower in HIV-infected (p = .03) pre-eclampsia. The latter had lower BMI (p =
      .007) and triceps skin-fold thickness (p < .001) than the HIV uninfected groups
      with a significant correlation between serum leptin and triceps skin-fold
      thickness (p < .001), indicative of less adipose tissue in HIV-infected women
      with consequently lower serum leptin. Thus, serum leptin levels are not
      indicative of increased placental production when pre-eclampsia is associated
      with HIV infection.

PMID- 27690696
TI  - Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off
      Target Transfection. Role of EZH2 in Adhesion Formation.
AB  - AIM OF THE STUDY: Adenovector encoding tissue plasminogen activator (tPA) was
      shown to reduce experimental peritoneal adhesion. We investigated the targeting
      potential of our modified adenovector, its ability to reduce adhesions and the
      epigenetic role of histone methyltransferase EZH2 in adhesion formation.
      MATERIALS AND METHODS: Control lacZ, nonmodified tPA or modified tPA vectors were
      instilled in the peritoneal cavity after injury in de novo adhesions or after
      lysis of adhesions in recurrent adhesions. Adhesion severity was scored and
      adhesions and liver tissues were examined for adenovirus E4 gene and tPA mRNA
      expression. Levels of tPA, plasminogen activator inhibitor-1 (PAI-1),
      transforming growth factor-beta1 (TGF-beta1), and EZH2 expression were measured.
      RESULTS: E4 transcripts were detected in adhesions of nonmodified and modified
      and in livers of nonmodified but not in livers of modified de novo adhesions.
      Both nonmodified (p = 0.021) and modified vectors (p = 0.036) reduced the
      severity of de novo adhesions compared to lacZ vector. Levels of tPA in
      nonmodified (p = 0.021) and modified adhesions (p = 0.001) were elevated while
      PAI-1 (p = 0.013 and p = 0.001, respectively) and TGF-beta1 levels (p = 0.002 and
      p = 0.016, respectively) were reduced compared with lacZ group. All vectors were
      not expressed in recurrent adhesions and severity score were not different among
      groups. EZH2 levels were elevated in de novo nontreated (p = 0.001) and was
      further increased in recurrent (p = 0.001) nontreated adhesions compared with
      noninjured peritoneum. CONCLUSION: Modified adenovirus successfully targeted de
      novo adhesions but not liver tissues and reduced the severity of de novo
      adhesions. EZH2 is involved in the development and progression of peritoneal
      adhesions.

PMID- 27690698
TI  - Allopurinol Protective Effect of Renal Ischemia by Downregulating TNF-alpha, IL
      1beta, and IL-6 Response.
AB  - Allopurinol is a well-known antioxidant that protects tissue against ischemia and
      reperfusion injury, blocking purine catabolism, and possibly reducing TNF-alpha
      and other cytokines. It also plays a significant role in reducing the
      inflammatory processes by inhibiting chemotaxis and other inflammatory mediators.
      The objective of this study was to define the role of allopurinol regarding
      kidney ischemic injury particularly as to its effect on inflammatory molecules
      such as TNF-alpha, IL-1beta, and IL-6 response. One hundred and twenty five rats
      were subjected to warm renal ischemia. Five more animals were included as sham.
      Animal survival and plasma levels of lipid peroxidation, myeloperoxidase, lactate
      dehydrogenase, glutathione, urea, creatinine, and cytokines were determined.
      Inflammatory parameters (TNF-alpha, IL-1beta, and IL-6) were measured in all
      groups by quantitative immunosorbent assay. Further, immunohistological and
      histopathological studies were carried out on animals treated prior to, or
      following reperfusion with 10 and 50 mg/kg of Allopurinol. The statistical
      analysis included ANOVA and Fisher test as well as chi2 test. Significance was
      reached at a p < 0.05. The results of this study indicated that Allopurinol
      protected against kidney ischemia-reperfusion injury since significantly better
      results of survival, biochemical analysis, and histopathological testing were
      observed in treated animals as compared to ischemic controls. In conclusion,
      Allopurinol protected ischemic kidneys through a mechanism associated with
      downregulation of TNF-alpha, IL-1 beta, and IL-6, in addition to other well-known
      effects such as decreased lipid peroxidation and neutrophil activity. It also
      increased antioxidant capacity and diminished endogenous peroxidase stain in
      renal ischemic tissue. Therefore, this experiment showed an effectiveness of
      allopurinol protection against proteomic and morphological damage.

PMID- 27690697
TI  - Antioxidant Effect of Ukrain Versus N-Acetylcysteine Against Acute Biliary
      Pancreatitis in An Experimental Rat Model.
AB  - : Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of
      acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC
      631570) and N-acetylcysteine (NAC) in rats with AP. MATERIALS AND METHODS: Forty
      male Sprague Dawley rats were divided into four groups: controls; AP; AP with
      NAC; and AP with Ukrain. AP was induced via the ligation of the bile-pancreatic
      duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP
      induction. Twenty-four hours after AP induction, animals were sacrificed and the
      pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and
      activity levels of tumor necrosis factor (TNF)-alpha, and myeloperoxidase (MPO)
      were measured in tissue samples. Total oxidant status (TOS), total antioxidant
      status (TAS), and total bilirubin, as well as activity levels of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were
      measured in serum samples. Pancreatic tissue histopathology was also evaluated.
      RESULTS: Test drugs reduced levels of MDA, NO, TNF-alpha, total bilirubin, AST,
      ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P
      < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes
      and decreased pancreatic damage scores compared with the AP group (P < 0.05).
      Both test drugs attenuated pancreatic damage, but the therapeutic effect was more
      pronounced in rats that received Ukrain than in those receiving NAC. CONCLUSIONS:
      These results suggest that treatment with Ukrain or NAC can reduce pancreatic
      damage via anti-inflammatory and antioxidant effects.

PMID- 27690699
TI  - Serum lipid profile and fatty acid composition of erythrocyte phospholipids in
      children and adolescents with primary hyperlipidemia.
AB  - This study aimed at characterizing the fatty acid (FA) composition of red blood
      cell (RBC) phospholipids in children and adolescents with primary hyperlipidemia,
      and to ascertain potential association with serum lipid profile and dietary
      factors. At this purpose, 54 probands aged 6-17 years were recruited. Subjects
      showed a low omega-3 index (eicosapentaenoic acid, EPA + docosahexaenoic acid,
      DHA <4%). Compared to males, females had a trend toward lower levels of total
      monounsaturated fatty acids (MUFA) and MUFA/saturated fatty acids (SFAs) ratio in
      RBCs. An inverse relationship between MUFA concentration in RBCs and serum
      cholesterol or HDL-C/triglycerides ratio was found. Omega-6 polyunsaturated fatty
      acids (n-6 PUFA) were positively associated to serum HDL-C levels, and inversely
      to dietary cholesterol. Fiber intake was positively associated with MUFA/SFA
      ratio. In conclusion, we provide the first experimental data on phospholipid FA
      composition of RBCs in hyperlipidemic children, showing sex differences and an
      overall low omega 3-index.

PMID- 27690700
TI  - The Role of Minimally Invasive Surgery in the Treatment of Lung Metastases.
AB  - INTRODUCTION: The ideal surgical approach for pulmonary metastasectomy remains
      controversial. Thoracoscopic surgery may offer advantages in quality of life
      outcomes, with equivalent oncologic long-term results. This study aimed to
      demonstrate the validity of video-assisted thoracoscopic surgery (VATS) in the
      treatment of lung metastases. METHODS: In all 224 patients who underwent 300 VATS
      metastasectomies from January 2000 to December 2013 were retrospectively
      reviewed. Sixty-nine patients underwent major resection (68 thoracoscopic
      lobectomies and one pneumonectomy) and 155 patients underwent a wedge
      resection/segmentectomy. Complete curative pulmonary resections were performed in
      219 (97%) cases. The Kaplan-Meier method was used to estimate survival curves.
      Univariate and subsequent multivariate Cox model regression were performed to
      identify independent factors of overall survival. RESULTS: One hundred eighty-six
      patients developed lung metastases from epithelial tumors, 28 from sarcomas,
      seven from melanomas, and three from germ cell tumors. The final pathological
      examination revealed no cases of R1 disease. After a mean follow-up of 40 months,
      118 patients (53%) had died. According to a multivariate analysis, a better
      prognosis was not observed for patients with a particular histological type; in
      addition, disease-free interval time, age, number of metastases, and type of
      surgery did not have any statistical influence on long-term survival.
      CONCLUSIONS: Thoracoscopic surgery is a safe and efficacious procedure, with a
      five-year overall survival that is equivalent to open surgery.

PMID- 27690701
TI  - Calcium phosphate: a substitute for aluminum adjuvants?
AB  - INTRODUCTION: Calcium phosphate was used as an adjuvant in France in diphtheria,
      tetanus, pertussis and poliomyelitis vaccines. It was later completely
      substituted by alum salts in the late 80's, but it still remains as an approved
      adjuvant for the World Health Organization for human vaccination. Area covered:
      Thus, calcium phosphate is now considered as one of the substances that could
      replace alum salts in vaccines. The aim of this paper is to draw a review of
      existing data on calcium phosphate as an adjuvant in order to bring out the
      strengths and weaknesses for its use on a large scale. Expert commentary: Calcium
      phosphate is a compound naturally present in the organism, safe and already used
      in human vaccination. Beyond comparisons with the other adjuvants, calcium
      phosphate represents a good candidate to replace or to complete alum salts as a
      vaccine adjuvant.

PMID- 27690702
TI  - Clinical Management of Community Acquired Pneumonia in the Elderly Patient.
AB  - INTRODUCTION: Community acquired pneumonia (CAP) is a major health problem in
      elderly persons and is associated with high morbidity and mortality. Areas
      covered: This article reviews the most recent publications relative to CAP in the
      elderly population, with a focus on epidemiology, prognostic factors, microbial
      etiology, therapy and prevention. The data discussed in this review were mainly
      obtained from a non-systematic review using Medline, and references from relevant
      articles. Expert Commentary: CAP can occur at any age, but its incidence and risk
      of death are linked to increasing age. Age-related changes in the immune system
      make this population more vulnerable to CAP. Mortality in hospitalized patients
      with CAP ranges from 10% to 12%. However, in the case of elderly patients,
      several studies have reported mortality rates of up to 25%. Pneumococcal and
      influenza vaccination comprise one of the most important preventive approaches
      for CAP in the elderly.

PMID- 27690703
TI  - A Novel Method for Evaluating Postoperative Adhesions in Rats.
AB  - : Purpose/Aim: Postoperative adhesions remain an undesirable and commonly
      symptomatic side effect of abdominopelvic surgeries. Animal models of
      postoperative adhesions typically yield heterogeneous adhesions throughout the
      abdominal cavity and are not easily quantified. Here we present a novel method of
      postoperative adhesion assessment and report its reliability and measurement
      error. MATERIALS AND METHODS: A model of cecal abrasion with partial sidewall
      attachment was performed on female rats. After 1, 2, 4, or 7 days of recovery,
      the rats were euthanized and their abdominopelvic cavities were systematically
      evaluated for postoperative adhesions. The necropsy was recorded through the
      surgical microscope. Four raters were trained to use a ballot to capture key
      factors of the adhesions as they viewed the recordings. Their ratings were
      compared for measurement error and reliability (using Bland-Altman plots and
      intraclass correlation coefficients, respectively) and for the ability to
      discriminate differences in experimental groups. A subset of the data was
      analyzed to determine practical utility. RESULTS: The rating system was shown to
      have low measurement error and high inter-rater reliability for all parameters
      measured. Applied practically, the system was able to discriminate groups in a
      manner that was expected. CONCLUSIONS: We have developed and validated a rating
      system for postoperative adhesions and shown that it can detect group
      differences. This method can be used to quantify postoperative adhesions in
      rodent models.

PMID- 27690704
TI  - A review of measles supplementary immunization activities and the implications
      for Pacific Island countries and territories.
AB  - INTRODUCTION: Standard measles control strategies include achieving high levels
      of measles vaccine coverage using routine delivery systems, supplemented by mass
      immunization campaigns as needed to close population immunity gaps. Areas
      covered: This review looks at how supplementary immunization activities (SIAs)
      have contributed to measles control globally, and asks whether such a strategy
      has a place in Pacific Islands today. Expert commentary: Very high coverage with
      two doses of measles vaccine seems to be the optimal strategy for controlling
      measles. By 2015, all but two Pacific Islands had introduced a second dose in the
      routine schedule; however, a number of countries have not yet reached high
      coverage with their second dose. The literature and the country reviews reported
      here suggest that a high coverage SIA combined with one dose of measles vaccine
      given in the routine system will also do the job. The arguments for and against
      the use of SIAs are complex, but it is clear that to be effective, SIAs need to
      be well designed to meet specific needs, must be carried out effectively and
      safely with very high coverage, and should, when possible, carry with them other
      public health interventions to make them even more cost-effective.

PMID- 27690705
TI  - Refinement of Tissue-Engineering Chamber Implantation in the Rat.
AB  - PURPOSE: Rodent in vivo models that successfully generate new adipose, muscle, or
      vascular tissue in a tissue-engineering chamber (TEC) has advanced in the last
      decade. In this article, technical refinements in these operative foreign body
      implantations have been described to improve the execution of animal models in a
      way so that they can reduce wastage of time and resources. MATERIALS & METHODS:
      Male Sprague-Dawley rats were studied and randomly divided into two equal sized
      groups. In each group, a different operative procedure was used for implanting
      the TEC. Twenty animals were operated with diagonal incisions in the groin
      region, followed by staples for wound closure after TEC implantation. The
      remaining 20 animals received longitudinal incisions in the abdominal region
      followed by wound closure with ongoing intradermal nonresorbable sutures and skin
      glue. The outcome of both procedures with regard to complications, animal growth,
      and experimental failure was compared. Statistical analysis was performed using
      the nonparametric chi-squared (chi2) test. RESULTS: Significant difference in
      wound dehiscence was recorded in Group I as compared to Group II (p = 0.0001).
      Consequently, 55% of the experiments had to be aborted in Group I and the animals
      were removed from the experiment. On the contrary, in Group II, all the animals
      could be kept. CONCLUSION: Median longitudinal incisions and thorough wound
      closure with ongoing intradermal nonresorbable sutures, followed by application
      of skin glue, are strongly recommended to prevent surgical site complications,
      such as wound dehiscence, animal harm, and failure of the individual experiment.

PMID- 27690707
TI  - Muscle strength and quality of life in patients with childhood cancer at early
      phase of primary treatment.
AB  - Cancer- and treatment-related side effects in patients with childhood cancer may
      cause limitations in motor performance affecting activities of daily living
      (ADLs). Data focusing on long-term effects are available, but little is known
      with regard to the short-term perspective. Therefore, the purpose of this study
      was to assess muscle strength performance and quality of life (QoL) in children
      and adolescents with cancer at the beginning of primary treatment. Forty children
      and adolescents aged 5-18 years (mean: 11.39 +/- 4.08 years) with different types
      of childhood cancer were enrolled. On average 36 +/- 20.5 days after diagnosis,
      strength performance in 7 muscle groups was assessed by handheld dynamometry.
      KINDL questionnaires were completed to evaluate QoL (children's self-report and
      parents' report). All parameters were compared with age- and gender-matched
      reference values. Patients with childhood cancer showed significantly lower
      strength values in all muscle groups (P < .01) compared with age- and gender
      matched controls. Most affected were the lower extremities, with a -57.1% +/-
      10.4%, median: -59.2%, minimum: -75.4%, maximum: -41.4% percentage deviation in
      knee flexion from healthy peers. Children themselves and parents assessed total
      QoL significantly below age- and gender-matched reference values (P < .01).
      Correlation between elbow flexion and self-reported QoL was detected. Broader
      correlations were found for the parents' report. Muscle weakness and decreased
      QoL in children and adolescents seem to persist already at the beginning of
      anticancer treatment. This underlines the need of counteracting measures, such as
      exercise intervention programs, starting as early as possible during the
      treatment process. Efforts on this topic are currently being carried out by our
      group.

PMID- 27690706
TI  - Families and medication use and adherence among Latinos with schizophrenia.
AB  - BACKGROUND: Medication nonadherence among Latinos with schizophrenia represents a
      significant treatment obstacle. Although some studies have examined patient and
      family perceptions of adherence, few have examined these perceptions together.
      However, such knowledge can provide a deeper understanding of how family
      processes may contribute to or impede adherence among underserved groups such as
      Latinos. AIMS: This study explored perceptions of medication and adherence among
      Latinos with schizophrenia and key family members. METHOD: Purposive sampling was
      used to collect data from 34 participants: 14 patients with schizophrenia
      receiving community-based mental health services in an urban public setting and
      20 key family members. Informed by grounded theory, semistructured interviews
      were analyzed by bilingual-bicultural team members. RESULTS: Salient themes
      emerged indicating facilitators of and obstacles to medication use. Specifically,
      challenges centered on medication side effects, autonomy and choice, and illness
      insight, whereas facilitators focused on family support and holistic views of
      treatment and empowerment. CONCLUSIONS: Because the majority of Spanish-speaking
      Latinos with schizophrenia live with family, it is important to examine family
      factors that may influence medication use. Findings suggest that patient and
      family perceptions of medication should be examined as part of the treatment
      process, particularly regarding issues of autonomy and choice.

PMID- 27690708
TI  - Characterization of mothers at risk of delivery at the limit of viability and
      factors related to infant survival.
AB  - OBJECTIVES: To determine the sociodemographic and clinical characteristics of
      mothers of infants at the limit of viability and to know the perinatal factors
      associated to infants' survival. METHOD: Single-center cohort study of mothers
      and newborns assisted in our tertiary care center (2004-2010). Demographic and
      perinatal variables were compared between mothers who gave birth  <=26 weeks GA
      and the general population. The association between perinatal factors and
      neonatal survival was studied by Cox regression analysis. RESULTS: Mothers of
      newborns  <=26 weeks (n = 136) had less education and pregnancy control. They had
      more frequently assisted reproductive technologies (ART) (5.2% versus 2.3%; p<
      0.05), multiple gestations (16.6% versus 2.1%; p < 0.05), pregnancy complications
      and C-section (39.7% versus 13.4%; p  < 0.001). After correcting for confounders,
      the perinatal factors independently associated with a variation in the risk of
      mortality were the administration of antenatal steroid [aHR (95%CI): 0.465 (0.254
      0.853), p = 0.013], singleton pregnancy [aHR (95%CI): 0.482 (0.279-0.834), p =
      0.009], infant's temperature on admission [aHR (95%CI): 0.642 (0.426-0.968), p =
      0.035] and CRIB score [aHR (95%CI): 1.151 (1.058-1.251), p  = 0.001].
      CONCLUSIONS: Mothers of preterm infants at the limit of viability had more ART,
      multiple pregnancies, obstetrical complications and C-section. Infants' survival
      was independently associated to antenatal steroids, singleton pregnancy,
      temperature on admission and CRIB score.

PMID- 27690709
TI  - Glomerular Glucocorticoid Receptors Expression and Clinicopathological Types of
      Childhood Nephrotic Syndrome.
AB  - Glucocorticoids are primary therapy of idiopathic nephrotic syndrome (INS).
      However, not all children respond to steroid therapy. We assessed glomerular
      glucocorticoid receptor expression in fifty-one children with INS and its
      relation to response to steroid therapy and to histopathological type. Clinical,
      laboratory and glomerular expression of glucocorticoid receptors were compared
      between groups with different steroid response. Glomerular glucocorticoid
      expression was slightly higher in controls than in minimal change early
      responders, which in turn was significantly higher than in minimal change late
      responders. There was significantly lower glomerular glucocorticoid receptor
      expression in steroid-resistance compared to early responders, late responders
      and controls. Glomerular glucocorticoid expression was significantly higher in
      all minimal change disease (MCD) compared to focal segmental glomerulosclerosis.
      In INS, response to glucocorticoid is dependent on glomerular expression of
      receptors and peripheral expression. Evaluation of glomerular glucocorticoid
      receptor expression at time of diagnosis of NS can predict response to steroid
      therapy.

PMID- 27690711
TI  - The factor structure of the mental health continuum-short form (MHC-SF) in
      Serbia: an evaluation using exploratory structural equation modeling.
AB  - BACKGROUND: The Mental Health Continuum-Short Form (MHC-SF) is a brief measure to
      assess emotional, social, and psychological well-being. AIMS: We examined the
      factor structure of the MHC-SF in Serbia. A secondary goal was to examine
      measurement invariance and latent mean differences across gender. METHOD: The
      methods of Confirmatory Factor Analysis (CFA) and Exploratory Structural Equation
      Modeling (ESEM) were used to investigate the factor structure of the scale in a
      large sample (N = 1883). We compared 1-, 2-, and 3-factor models of mental well
      being. RESULTS: The results supported the superiority of the 3-factor model of
      well-being over the alternatives. ESEM yielded better fit with the data and
      considerably smaller factor correlations than did CFA. ESEM also uncovered a
      number of cross-loadings in the MHC-SF. Full measurement invariance was
      established across gender, yet no significant gender differences were identified
      in the latent means. CONCLUSIONS: These results indicate that emotional, social,
      and psychological well-being represents correlated yet distinct factors in
      Serbia. The results also suggest that ESEM is a more appropriate method than CFA
      for examining the factor structure of mental well-being. The contributions of
      ESEM to current debates surrounding the distinction between hedonic and
      eudaimonic well-being are discussed.

PMID- 27690710
TI  - Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus
      other basal insulins in insulin-naive patients with type 2 diabetes.
AB  - OBJECTIVE: This study aims to compare the effectiveness of insulin glargine 300
      U/mL (Gla-300) with its accompanying patient support program with that of other
      basal insulin and available patient support programs in patients with type 2
      diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare
      Effectiveness Data and Information Set) individualized glycemic targets without
      documented symptomatic hypoglycemia. METHODS: Achieve Control is a US-based,
      multicenter, randomized, open-label, active-controlled, parallel group pragmatic
      Phase IV trial in insulin-naive patients with T2D uncontrolled on >=2 oral
      antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP
      1 RA). Inclusion criteria include a diagnosis of T2D, age >=18 years, and
      glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to
      either the Gla-300 or other basal insulin group. The primary end point is the
      proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in
      patients with comorbidities or aged >=65 years; <7.0% [58 mmol/mol] in all other
      patients) without occurrence of symptomatic hypoglycemia (blood glucose <=70
      mg/dL) from baseline to 6 months. Secondary end points include rates of
      documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change
      from baseline in HbA1c, fasting glucose, and body weight; treatment persistence;
      patient-reported outcomes; and healthcare resource utilization. Planned
      enrollment is 3270 patients across approximately 400 clinical sites. CONCLUSION:
      Pragmatic clinical trials offer the potential to assess comparative effectiveness
      in broadly based patient populations receiving care (with or without a
      corresponding educational support program) in real-world clinical settings. The
      results of Achieve Control should elucidate the benefits of management of T2D
      with Gla-300 versus other basal insulins in terms of patient outcomes,
      experiences, and perceptions, and its impact on healthcare resource utilization
      and cost. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is
      NCT02451137.

PMID- 27690712
TI  - Australian mental health nurses' perspectives about the identification and
      management of antipsychotic medication side effects: a cross-sectional survey.
AB  - BACKGROUND: Currently, little is known about mental health nurses' management of
      antipsychotic medication side effects. AIMS: This study examined how Australian
      mental health nurses' attitudes and service processes influence the assessment of
      antipsychotic medication side effects. METHODS: Participants were included if
      they were registered nurses in Australian mental health settings. An online
      questionnaire was distributed via email. Multivariate logistic regression was
      used to examine associations between attitudes and awareness, and use of
      antipsychotic medication assessment tools. RESULTS: Only one quarter of the
      respondents were currently using a tool. In cases where the service had a clear
      system for agreeing responsibility about monitoring consumers between primary and
      secondary care, respondents were three times more likely to still be using one or
      more tool. When the service had reliable systems in place to remind staff that
      side effect assessments were due, respondents were five times more likely to
      continue using assessment tools. CONCLUSION: Australian mental nurses are not
      routinely using antipsychotic medication side effect assessment tools. The
      routine use of assessment tools would improve if systems were implemented to
      enhance their use.

PMID- 27690713
TI  - Targeting microsomal triglyceride transfer protein and lipoprotein assembly to
      treat homozygous familial hypercholesterolemia.
AB  - Homozygous familial hypercholesterolemia (HoFH) is a polygenic disease arising
      from defects in the clearance of plasma low-density lipoprotein (LDL), which
      results in extremely elevated plasma LDL cholesterol (LDL-C) and increased risk
      of atherosclerosis, coronary heart disease, and premature death. Conventional
      lipid-lowering therapies, such as statins and ezetimibe, are ineffective at
      lowering plasma cholesterol to safe levels in these patients. Other therapeutic
      options, such as LDL apheresis and liver transplantation, are inconvenient,
      costly, and not readily available. Recently, lomitapide was approved by the
      Federal Drug Administration as an adjunct therapy for the treatment of HoFH.
      Lomitapide inhibits microsomal triglyceride transfer protein (MTP), reduces
      lipoprotein assembly and secretion, and lowers plasma cholesterol levels by over
      50%. Here, we explain the steps involved in lipoprotein assembly, summarize the
      role of MTP in lipoprotein assembly, explore the clinical and molecular basis of
      HoFH, and review pre-clinical studies and clinical trials with lomitapide and
      other MTP inhibitors for the treatment of HoFH. In addition, ongoing research and
      new approaches underway for better treatment modalities are discussed.

PMID- 27690714
TI  - Can EMS Providers Provide Appropriate Tidal Volumes in a Simulated Adult-sized
      Patient with a Pediatric-sized Bag-Valve-Mask?
AB  - INTRODUCTION: In the prehospital setting, Emergency Medical Services (EMS)
      professionals rely on providing positive pressure ventilation with a bag-valve
      mask (BVM). Multiple emergency medicine and critical care studies have shown that
      lung-protective ventilation protocols reduce morbidity and mortality. Our primary
      objective was to determine if a group of EMS professionals could provide
      ventilations with a smaller BVM that would be sufficient to ventilate patients.
      Secondary objectives included 1) if the pediatric bag provided volumes similar to
      lung-protective ventilation in the hospital setting and 2) compare volumes
      provided to the patient depending on the type of airway (mask, King tube, and
      intubation). METHODS: Using a patient simulator of a head and thorax that was
      able to record respiratory rate, tidal volume, peak pressure, and minute volume
      via a laptop computer, participants were asked to ventilate the simulator during
      six 1-minute ventilation tests. The first scenario was BVM ventilation with an
      oropharyngeal airway in place ventilating with both an adult- and pediatric-sized
      BVM, the second scenario had a supraglottic airway and both bags, and the third
      scenario had an endotracheal tube and both bags. Participants were enrolled in
      convenience manner while they were on-duty and the research staff was able to
      travel to their stations. Prior to enrolling, participants were not given any
      additional training on ventilation skills. RESULTS: We enrolled 50 providers from
      a large, busy, urban fire-based EMS agency with 14.96 (SD = 9.92) mean years of
      experience. Only 1.5% of all breaths delivered with the pediatric BVM during the
      ventilation scenarios were below the recommended tidal volume. A greater
      percentage of breaths delivered in the recommended range occurred when the
      pediatric BVM was used (17.5% vs 5.1%, p < 0.001). Median volumes for each
      scenario were 570.5mL, 664.0mL, 663.0mL for the pediatric BMV and 796.0mL,
      994.5mL, 981.5mL for the adult BVM. In all three categories of airway devices,
      the pediatric BVM provided lower median tidal volumes (p < 0.001). CONCLUSION:
      The study suggests that ventilating an adult patient is possible with a smaller,
      pediatric-sized BVM. The tidal volumes recorded with the pediatric BVM were more
      consistent with lung-protective ventilation volumes.

PMID- 27690715
TI  - Economic and clinical burden of opioid-induced nausea and vomiting.
AB  - Opioids are the standard of care for treating moderate-to-severe pain; however,
      their efficacy can be limited by adverse events (AEs), including nausea and
      vomiting. Opioid-induced nausea and vomiting (OINV) is an inherent adverse effect
      of opioid treatment, exerting effects centrally and peripherally. Opioid-related
      AEs can impact treatment adherence and discontinuation, which can result in
      inadequate pain management. OINV may persist long-term, negatively affecting
      patient functional outcomes, physical and mental health, patient satisfaction,
      and overall costs of treatment. Multiple factors may contribute to OINV,
      including activation of opioid receptors in the chemoreceptor trigger zone,
      vestibular apparatus, and gastrointestinal tract. Prophylactic or early treatment
      with antiemetics may be appropriate for patients who are at high risk for OINV.

PMID- 27690716
TI  - Development of a combined radiation and full thickness burn injury minipig model
      to study the effects of uncultured adipose-derived regenerative cell therapy in
      wound healing.
AB  - PURPOSE: To develop an approach that models the cutaneous healing that occurs in
      a patient with full thickness thermal burn injury complicated by total body
      radiation exposure sufficient to induce sub-lethal prodromal symptoms. An
      assessment of the effects of an autologous cell therapy on wound healing on
      thermal burn injury with concomitant radiation exposure was used to validate the
      utility of the model. METHODS: Gottingen minipigs were subjected to a 1.2 Gy
      total body irradiation by exposure to a 6 MV X-ray linear accelerator followed by
      ~10 cm2 full thickness burns (pre-heated brass block with calibrated spring).
      Three days after injury, wounds were excised to the underlying fascia and each
      animal was randomized to receive treatment with autologous adipose-derived
      regenerative cells (ADRC) delivered by local or intravenous injection, or vehicle
      control. Blood counts were used to assess radiation-induced marrow suppression.
      All animals were followed using digital imaging to assess wound healing. Full
      thickness biopsies were obtained at 7, 14, 21 and 30 days' post-treatment.
      RESULTS: Compared to animals receiving burn injury alone, significant transient
      neutropenia and thrombocytopenia were observed in irradiated subjects with
      average neutrophil nadir of 0.79 * 103/MUl (day 15) and platelet nadir of 60 *
      103/MUl (day 12). Wound closure through a combination of contraction and
      epithelialization from the wound edges occurred over a period of approximately 28
      days' post excision and treatment. Re-epithelialization was accelerated in wounds
      treated with ADRC (mean 3.5-fold increase at 2 weeks post-treatment relative to
      control). This acceleration was accompanied by an average 67% increase in blood
      vessel density and 30% increase in matrix (collagen) deposition. Similar results
      were observed when ADRC were injected either directly into the wound or by
      intravenous administration. CONCLUSIONS: Although preliminary, this study
      provides a reproducible minipig model of thermal burn injury complicated by
      myelosuppressive total body irradiation that utilizes standardized procedures to
      evaluate novel countermeasures for potential use following attack by an
      improvised nuclear device.

PMID- 27690717
TI  - The glycosylation of the extracellular loop of beta2 subunits diversifies
      functional phenotypes of BK Channels.
AB  - Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels
      are composed of a pore-forming alpha subunit (Slo) and 4 types of auxiliary beta
      subunits or just a pore-forming alpha subunit. Although multiple N-linked
      glycosylation sites in the extracellular loop of beta subunits have been
      identified, very little is known about how glycosylation influences the structure
      and function of BK channels. Using a combination of site-directed mutagenesis,
      western blot and patch-clamp recordings, we demonstrated that 3 sites in the
      extracellular loop of beta2 subunit are N-glycosylated (N-X-T/S at N88, N96 and
      N119). Glycosylation of these sites strongly and differentially regulate gating
      kinetics, outward rectification, toxin sensitivity and physical association
      between the alpha and beta2 subunits. We constructed a model and used molecular
      dynamics (MD) to simulate how the glycosylation facilitates the association of
      alpha/beta2 subunits and modulates the dimension of the extracellular cavum above
      the pore of the channel, ultimately to modify biophysical and pharmacological
      properties of BK channels. Our results suggest that N-glycosylation of beta2
      subunits plays crucial roles in imparting functional heterogeneity of BK
      channels, and is potentially involved in the pathological phenotypes of
      carbohydrate metabolic diseases.

PMID- 27690718
TI  - Water or realistic compositions in proton radiotherapy? An analytical study.
AB  - PURPOSE: Pre-clinical tests and simulation studies for radiotherapy are generally
      carried out using water or simplified materials. Investigating the effects of
      defining compositionally realistic media in proton transport studies was the
      objective of this work. Accurate modeling of the Bragg curve is a fundamental
      requirement for such a study. METHODS AND MATERIALS: An equation previously
      validated by experiments provides an appropriate analytical method for proton
      dose calculation in depth of the target. Owing to the dependency on protons
      ranges and the probability of undergoing non-elastic nuclear interactions (NNI),
      this formula comprises three parameters with values specified for initial proton
      energy and for the target material. As a result, knowledge of the depth-dose
      distribution using this analytical model is limited to the materials for which
      the data has been provided in nuclear data tables. In this study, we used our
      general formulas for calculating the protons ranges and the probability of
      undergoing NNI in desired compounds and mixtures with an arbitrary number of
      constituent elements. Furthermore, the protons dose distribution in the depth of
      these targets was leading off with determining the parameters appeared in the
      employed model using our mathematically easy to handle relations. For a number of
      tissues which may be of interest in proton radiotherapy studies but are missing
      in reference data tables, the mentioned parameters were calculated. Moreover, the
      resultant values for the protons ranges and the probability of undergoing NNIs
      were compared with those in water. RESULTS: The results showed that the
      differences between the position of Bragg peaks in water and realistic media
      considered in this study were energy dependent, and ranged between a few
      millimeters. For proton beams of arbitrary chosen initial energies, the maximum
      dose delivered to the realistic media varied between about -0.02-4.42% in
      comparison with that to water. CONCLUSIONS: The effects observed (both in
      penetration and in the magnitude of the Bragg peaks) may be overshadowed by the
      different dose prescriptions depending on the quality of the treatment planning
      system, and dosimetry protocols used at the various therapy centers.

PMID- 27690719
TI  - Gold nanoparticles in combination with megavoltage radiation energy increased
      radiosensitization and apoptosis in colon cancer HT-29 cells.
AB  - PURPOSE: Gold nanoparticles (GNP) act as a radiosensitizer in radiation therapy.
      However, recent studies have shown contradictory evidence in terms of
      radiosensitization in the presence of GNP combined with X-ray megavoltage energy
      (MV) on different cell types. In this study, the effect of GNP on
      radiosensitization enhancement of HT-29 human colorectal cancer cells at MV X-ray
      energy was evaluated. MATERIALS AND METHODS: The cytotoxicity and
      radiosensitization of GNP were evaluated in HT-29 human colorectal cancer cells
      by MTS-assay and multiple MTS-assay, respectively. Cellular uptake was assayed
      using graphite furnace atomic absorption spectrometry (GFAAS). Apoptosis and cell
      cycle progression were determined by an Annexin V-FITC/propidium iodide (PI) kit
      and PI/RNase solution with flow cytometry, respectively. RESULTS: Results showed
      that the cell viability of the HT-29 cells was not influenced by exposure to
      different concentrations of GNP (10-100 MUM). GNP alone did not affect the cell
      cycle progression and apoptosis. In contrast, GNP, in combination with radiation
      (9 MV), induced more apoptosis. The interaction of GNP with MV energy resulted in
      a significant radiosensitization enhancement compared with irradiation alone.
      CONCLUSION: It was concluded that GNP may work as bio-inert material on HT-29
      cancer cells and their enhancement of radiosensitization may be due to increase
      in the absorbed irradiation dose.

PMID- 27690720
TI  - Alpha-fetoprotein and Fanconi Anemia: Relevance to DNA Repair and Breast Cancer
      Susceptibility.
AB  - Elevations of serum alpha-fetoprotein (sAFP) have been reported in fetal and
      infant states of anemia. Fanconi anemia (FA) belongs to a family of genetic
      instability disorders which lack the capability to repair DNA breaks. The lesion
      occurs at a checkpoint regulatory step of the G2 to mitotic transition, allowing
      FA cells to override cell-cycle arrest. FA DNA repair pathways contain
      complementation groups known as FANC proteins. FANC proteins form multi-protein
      complexes with BRCA proteins and are involved in homologous DNA repair. An
      impaired cascade in these events imparts an increased breast cancer
      susceptibility to female FA patients. Elevations of sAFP have availed this fetal
      protein to serve as a biomarker for FA disease. However, the origin of the
      synthesis of sAFA has not been determined in FA patients. We hypothesize that
      hematopoietic multipotent progenitor stem cells in the bone marrow are the source
      of sAFP production in FA patients.

PMID- 27690721
TI  - Contemporary challenges and opportunities in the diagnosis and outbreak detection
      of multidrug-resistant infectious disease.
AB  - INTRODUCTION: The dissemination of multi-drug resistant bacteria (MDRB) has
      become a major public health concern worldwide because of the increase in
      infections caused by MDRB, the difficulty in treating them, and expenditures in
      patient care. Areas covered: We have reviewed challenges and contemporary
      opportunities for rapidly confronting infections caused by MDRB in the 21st
      century, including surveillance, detection, identification of resistance
      mechanisms, and action steps. Expert commentary: In this context, the first
      critical point for clinical microbiologists is to be able to rapidly detect an
      abnormal event, an outbreak and/or the spread of a MDRB with surveillance tools
      so that healthcare policies and therapies adapted to a new stochastic event that
      will certainly occur again in the future can be implemented.

PMID- 27690722
TI  - Differential neutrophil chemotactic response towards IL-8 and bacterial N-formyl
      peptides in term newborn infants.
AB  - BACKGROUND: A prerequisite for an effective innate immunity is the migrative
      ability of neutrophils to respond to inflammatory and infectious agents such as
      the intermediate interleukin (IL)-8 and the end-target formyl-methionyl-leucyl
      phenylalanine (fMLP) chemoattractants. The aim was to study the chemotactic
      capacity of neutrophils from newborn infants and adults in response to IL-8 and
      the bacterial peptide fMLP. METHODS: In the under-agarose cell migration assay,
      isolated leukocytes from healthy adults and from cord blood of healthy term
      newborn infants were studied with dose responses towards IL-8 and fMLP. The same
      number of leukocytes (1 * 105 cells), with the same distribution of neutrophils
      and monocytes, were analyzed in neonates and adults. Chemotaxis was distinguished
      from randomly migrating neutrophils, and the neutrophil pattern of migration,
      i.e. the migration distance and the number of migrating neutrophils per distance,
      was evaluated. RESULTS: In comparison to adults, fewer neutrophils from newborn
      infants migrated towards IL-8 and for a shorter distance (P < .01, respectively).
      The number of neutrophils migrating to different gradients of fMLP, the distance
      they migrated, and the correlation between the number and the distance were the
      same for neonates and adults. Random migration did not differ in any instance.
      CONCLUSION: Chemotaxis of neutrophils from newborn infants was as co-ordinated as
      neutrophils from adults in response to fMLP, whereas the response to IL-8 was
      reduced. The differential response of neutrophils from neonates to intermediate
      and end-target chemoattractants could indicate a reduced infectious response.

PMID- 27690723
TI  - The relationship between: occupational status, biological condition and androgen
      hormone level among Polish adult men: the Wroclaw Male Study.
AB  - Population health and its determinants are one of the major challenges to social
      and economic policy. The aim of this study was to investigate the relationship
      between occupational activity and biological condition in adult working Polish
      men. The participants of the study were 300 men (30-65 years), healthy
      inhabitants of the city of Wroclaw, Poland. Seventeen measures of biological
      condition were examined. The subjects were divided into three different
      occupational groups: professionals, soldiers and skilled workers. A comparison of
      biological age profiles of three occupational groups showed that in the majority
      of characteristics, professionals had the youngest biological age, whereas
      skilled workers had the highest biological age. The results for soldiers were not
      as unambiguous, but biological parameters were generally closer to those for
      professionals. Inborn biological predispositions and long-term impact of the
      working environment can influence on the biological condition of various
      professional groups. Knowledge of the determinants of biological condition might
      result in efficient use of predisposition to work or may be of help in extending
      their time of work ability.

PMID- 27690724
TI  - Correlation of the leucocyte count with traditional and non-traditional
      components of metabolic syndrome.
AB  - OBJECTIVES: To investigate correlation of the white blood cell (WBC) and its
      subtype count with the traditional and non-traditional components of the
      metabolic syndrome. METHODS: Between January 2012 and December 2013, 18,222
      people were enrolled in this study. The height, weight, body mass index (BMI) and
      blood pressure were measured, and blood samples were tested for all subjects
      after an overnight fast. The count of WBC and its subtypes, total cholesterol,
      triglyceride, high density lipoprotein (HDL), low-density lipoprotein,
      aminotransferases, fibrinogen, uric acid, and fasting blood glucose were all
      assessed. RESULTS: Metabolic syndrome was found in 2502 of 18,222 healthy Chinese
      people (16.41%). The prevalence of metabolic syndrome was 22.61% for men
      significantly (P < 0.05) greater than for women (6.83%). The prevalence of
      obesity, hypertension, hyperglycemia and hyperlipidemia was significantly (P <
      0.001) higher in people with than without metabolic syndrome. With increase of
      the WBC count, BMI, systolic and diastolic pressure, fasting blood glucose,
      triglyceride, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase,
      glutamyltranspetidase, blood urea nitrogen fibrinogen and uric acid all went up
      significantly (P < 0.001) while HDL decreased significantly (P < 0.05). The
      creatinine remained relatively sTable After adjustment of age, sex, alcoholic
      drinking and education, the metabolic components of obesity, hypertension,
      diabetes and hyperlipidemia rose significantly (P < 0.05) positively with
      increased counts of the total WBC, neutrophil and lymphocyte, and the WBC and its
      subtypes were an independent risk factor for metabolic syndrome. CONCLUSION:
      Aminotransferases, fibrinogen and uric acid all significantly increase with
      increased WBC count in a dose-dependent manner. Increased counts of the total WBC
      and its subtypes are positively associated with presence of metabolic syndrome.

PMID- 27690725
TI  - Histological chorioamnionitis in preterm prelabor rupture of the membranes is
      associated with increased expression of galectin-3 by amniotic epithelium.
AB  - PURPOSE: Gal-3, which can regulate immune responses upon infection and
      inflammation, was not studied so far in intrauterine infection leading to preterm
      prelabor rupture of the membranes (PPROM), although gal-1 was reported to be
      implicated in the process. Gal-3 mRNA and protein expression in amnion and its
      changes during histological chorioamnionitis were studied here. MATERIALS AND
      METHODS: Fetal membranes were obtained from women with PPROM with (n =15) and
      without histological chorioamnionitis (n =15) during second and third trimester.
      Immunohistochemical reactivity was evaluated semiquantitatively and analyzed
      using t-test. Galectin profile of amniotic epithelia was determined by polymerase
      chain reaction (PCR) and change assessed in gal-3 in PPROM with (n =5) or without
      histological chorioamnionitis (n =5) by real-time PCR. RESULTS: Human amniotic
      epithelium was found to express gal-1, gal-3, gal-7 and gal-8 mRNA. Gal-3 mRNA
      and protein is increased in fetal membranes and in the amniotic epithelium in
      patients with chorionamnionitis. CONCLUSION: Histological chorioamnionitis is
      associated with increased gal-3 expression and strong immunoreactivity of the
      amnion. Gal-3 may participate in the regulation of the inflammatory responses to
      chorioamniotic infection and/or direct interaction with pathogens.

PMID- 27690726
TI  - Can Human Recombinant Epidermal Growth Factor Improve Ischemia and Induce Healing
      of Anastomosis in an Experimental Study in a Rabbit Model?
AB  - PURPOSE: Anastomotic leaks following intestinal operations may cause devastating
      effects on patients. Ischemia may also occur at the intestinal walls in the
      presence of strangulations. In this study, we examined the effects of human
      recombinant (Hr)-epidermal growth factor (EGF) given at a single intramural dose
      into the intestinal walls and daily intraperitoneal cavity on ischemia and the
      healing process of anastomosis. MATERIALS AND METHODS: Sixteen male New Zeland
      white rabbits were randomly divided into four groups (n = 4 in each group). In
      Group 1, two different segments of ileum were identified and, then, transected
      and the free ends were sutured each other. In the other groups, ischemia was
      induced by ligating the mesenteric vascular arcade. After the ischemic induction,
      Group 2 received intramural injections of %0.9 saline, Group 3 received
      intramural injections of a single dose of EGF, and Group 4 received intramural
      and intraperitoneal injections of EGF. Bursting pressures and tissue
      hydroxyproline levels were analyzed. Necrosis, fibroblastic activity, collagen
      deposition and neovascularization were also studied. RESULTS: The mean levels of
      bursting pressures in Group 4 (148.6 +/- 25.3 mmHg) were higher than Group 2 (70
      +/- 21.5 mmHg) (p = 0.001). The mean level of bursting pressures was not
      statistically significant between Group 1 (170.1 +/- 35 mmHg) and Group 4 (p =
      0.073). Hydroxyproline levels in Group 2 were lower than Groups 3 and 4. There
      was a statistically significant difference in the mucosal ischemia, mucosal
      healing and degree of adhesion, but not in the mural anastomotic healing among
      the groups. CONCLUSIONS: Intramural injection with daily intraperitoneal
      administration of low-dose EGF enhances the bursting pressure and collagen
      accumulation in ischemic anastomosis, improving many histological variables
      associated with ischemic intestinal anastomosis.

PMID- 27690727
TI  - Cord blood erythropoietin and cord blood nucleated red blood cells for prediction
      of adverse neonatal outcome associated with maternal obesity in term pregnancy:
      prospective cohort study.
AB  - OBJECTIVE: To determine the adverse pregnancy outcomes associated with maternal
      pre-pregnancy overweight and obesity and we measure cord blood erythropoietin and
      NRBC count as indices of hypoxia and predictors of neonatal outcome. STUDY
      DESIGN: This prospective cohort study was done in Minia University Hospital,
      carried out from May 2015 to April 2016. Two hundred and seventy full-term
      neonates born to mothers of various body mass indices were included. Excluded
      were neonates with major factors known to be associated with a potential increase
      in fetal erythropoiesis. Pre-pregnancy maternal BMI was calculated from
      maternally reported weight and height. Cord blood erythropoietin and nucleated
      red blood cells were measured. RESULTS: There is a significant increase of
      various adverse pregnancy outcomes as cesarean section. Postpartum hemorrhage and
      macrosomia with the increase of maternal pre-pregnancy BMI. Significant positive
      correlations between cord blood erythropoietin and nucleated red blood cells with
      maternal BMI. CONCLUSION: The increase in the maternal pre-pregnancy BMI is
      associated with poor pregnancy outcomes. Cord blood erythropoietin and nucleated
      red blood cells can predict the poor neonatal outcome.

PMID- 27690728
TI  - Vacuum erection device in treatment of organic erectile dysfunction and penile
      vascular differences between patients with DM type I and DM type II.
AB  - The aim of this study is to investigate changes in the vascular system and
      hemodynamics between patients with organic erectile dysfunction (ED) (DM type I
      and II), as well as to compare the quality of sexual life between those two
      groups after the treatment with vacuum erection device (VED). Study enrolled 50
      males with DM, aged from 35 to 67 years, who have attended the urologic clinic
      due to inability to attain and maintain an erection of the penis sufficient to
      permit satisfactory sexual intercourse. Patients were using VED and six months
      later were assessed for therapy results. The International Index of Erectile
      Function (IIEF) was used to quantify erectile dysfunction. Alprostadil injection
      test was also used, with Doppler color flow imaging system, to evaluate the peak
      systolic velocity (PSV) and diameter of cavernosal artery (DCA). Significantly
      higher values of PSV were obtained in patients with DM type II. Also, DCA showed
      significant difference between two groups of patients. There was significant
      improvement in three items of IIEF after six months of treatment among both
      groups of examinees. Patients with DM type I had more serious risk for
      development of arteriogenic ED. VED could be a good alternative therapy for
      patients who denied peroral therapy.

PMID- 27690731
TI  - Corrigendum.

PMID- 27690729
TI  - Endothelin-1 receptor drives invadopodia: Exploiting how beta-arrestin-1 guides
      the way.
AB  - Metastatization is a complex multistep process requiring fine-tuned regulated
      cytoskeleton re-modeling, mediated by the cross-talk of actin with interacting
      partners, such as the Rho GTPases. Our expanding knowledge of invadopodia, small
      invasive membrane protrusions composed of a core of F-actin, actin regulators and
      actin-binding proteins, and hotspots for secretion of extracellular matrix (ECM)
      proteinases, contributes to clarify critical steps of the metastatic program.
      Growth factor receptors and their intermediate signaling molecules, along with
      matrix adhesion and rigidity, pH and hypoxia, act as drivers of cytoskeleton
      changes and invadopodia formation. We recently pro-posed a novel route map by
      which cancer cells regulates invadopodia dynamics supporting metastasis as
      response to the endothelin A receptor (ETAR), among the highly druggable G
      protein coupled receptors in cancer. The metastatic behavior exhibited by ovarian
      cancer cells overe-xpressing ETAR is now explained by the interplay with beta
      arrestin1 (beta-arr1), a scaffold protein acting as signal-integrating module of
      RhoC and cofilin signaling for specific invadopodia formation, accomplished by
      its interaction with a Rho guanine nucleotide exchange factor (GEF), PDZ-RhoGEF,
      in a G-protein independent manner. Here, we summarize this novel activation of
      the RhoC pathway from ETAR/beta-arr1 signaling that may be exploited
      therapeutically and discuss new perspectives for future directions of
      investigations.

PMID- 27690730
TI  - Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in
      human colon cancer cells.
AB  - Recently, we showed that the metal chelator TPEN targets colon cancer cells
      through redox cycling of copper. Here, we studied the DNA damage potential of
      TPEN and deciphered the role of Chk1, ATM and DNA-PK in TPEN-induced toxicity in
      3 human colon cancer cell lines, HCT116, SW480 and HT29. We also investigated the
      role of reactive oxygen species (ROS) in TPEN-induced DNA damage. TPEN reduced
      cell viability in a dose- and time-dependent manner. Cytotoxicity was associated
      with significant DNA damage and higher expression of gamma-H2AX protein and
      activation of ATM/ATR signaling pathway. Cell death by TPEN was dependent on ROS
      generation as evidenced by the reversal of cell viability, and DNA damage and the
      abrogation of gamma-H2AX levels in the presence of antioxidants. Treatment with
      antioxidants, however, failed to reverse cytotoxicity at high TPEN concentrations
      (10uM). TPEN-induced cell death was also dependent on the redox cycling of copper
      since the copper chelator neocuproine inhibited DNA damage and reduced pChk1,
      gamma-H2AX, and ATM protein expression. Cell death by low TPEN concentrations,
      involved ATM/ATR signaling in all 3 cell lines, since pre-incubation with
      specific inhibitors of ATM and DNA-PK led to the recovery of cells from TPEN
      induced DNA damage. In addition, siRNA silencing of Chk1, DNA-PK and ATM
      abrogated the expression of gamma-H2AX and reversed cell death, suggesting that
      Chk1 and DNA-PK mediate TPEN-induced cytotoxicity in colon cancer cells. This
      study shows for the first time the involvement of Chk1, DNA-PK and ATM in TPEN
      induced DNA damage and confirms our previous findings that ROS generation and the
      redox cycling of copper in response to TPEN are the main mechanisms by which this
      compound induces cell death in human colon cancer cells. Inhibition of ATM or DNA
      PK did not reverse cytotoxicity at high TPEN concentrations that cause excessive
      levels of ROS and irreversible cellular damage.

PMID- 27690732
TI  - "The roots" of selenium toxicity: A new concept.
AB  - Elevated levels of selenium (Se) cause toxicity in non-accumulator plant species.
      The primary reasons for toxic Se effect have been considered to be selenoprotein
      accumulation and oxidative stress. However, based on our recent paper in Plant
      Cell Reports and previous literature data we suggest that disturbances in the
      homeostasis of both reactive oxygen and nitrogen species result in selenium
      induced nitro-oxidative stress, contributing to toxicity. The most characteristic
      symptom of Se exposure is the inhibited root elongation which is partly caused by
      hormonal disturbances. Our recent paper suggests the involvement of cytokinin in
      selenium stress sensing of the root systemAltogether, the aim of this Addendum is
      to present reactive nitrogen species and phytohormones as new players in plant
      selenium toxicity.

PMID- 27690733
TI  - Influence of diosmin on the metabolism and disposition of carbamazepine in
      healthy subjects.
AB  - 1. Carbamazepine (CBZ) is an antiepileptic drug with narrow therapeutic window
      and administration in humans receiving long-term therapy with diosmin (DSN) may
      occur, which leads to CYP3A4-mediated drug interactions. The purpose of the
      present study was to assess the influence of DSN on the metabolism and
      pharmacokinetics of CBZ in healthy volunteers. 2. An open-label, sequential, two
      period study was conducted in 12 healthy male volunteers. A single dose of DSN
      500 mg was administered once daily for 10 days during treatment phase. A single
      dose of CBZ 200 mg was administered during control and after treatment phases
      under fasting conditions. The blood samples were collected after CBZ dosing at
      predetermined time intervals and analyzed by LC-MS/MS. 3. Treatment with DSN
      significantly enhanced the maximum plasma concentration (Cmax), area under the
      curve (AUC), half-life (t1/2) and significantly decreased the apparent oral
      clearance (CL/F) and elimination rate constant (Kel) of CBZ. On the other hand,
      treatment with DSN significantly decreased the Cmax and AUC of carbamazepine 10,
      11-epoxide (CBZE). Furthermore, treatment with DSN significantly decreased the
      metabolite to parent ratios of Cmax and AUC, indicating the reduced metabolism of
      CBZ to CBZE. 4. The results suggest that the altered CYP3A4 enzyme activity and
      pharmacokinetics of CBZ might be attributed to DSN-mediated inhibition of CYP3A4
      enzyme, which indicates pharmacokinetic interaction present between DSN and CBZ.
      Therefore, we conclude that DSN has an inhibiting effect on the metabolism and
      disposition of CBZ.

PMID- 27690734
TI  - Quality evaluation for the surveillance system of human prion diseases in China
      based on the data from 2010 to 2016.
AB  - The surveillance of CJD or human prion diseases (PrDs) has been conducted for 10
      y in China. To evaluate the quality of China CJD surveillance system, the
      collections of the clinical and epidemiological information, the sampling, the
      clinical examinations and laboratory tests and follow-up survey were separately
      analyzed based on the data from 2010 to 2015. The obtaining rates of clinical
      information table, epidemiological-information table, sample inspection sheet and
      medical record of the referring patients from reporting units to the center of
      CJD surveillance maintained or reached at very high levels, being close to 100%
      in the past 3 y. 93.82%, 85.23%, 96.21% and 94.70% of the reported cases had the
      data of MRI, EEG, CSF 14-3-3 and PRNP sequencing, respectively. Follow-up surveys
      were conducted in about 50% cases in 2010 and 2011, 93.39% cases in 2012 and 100%
      cases in the last 3 y. High obtaining rates of the clinical and epidemiological
      data, high conducting rates of the relevant clinical examinations and laboratory
      tests, high performing rates of follow-up survey for every referring case reflect
      a good implemental capacity in China CJD surveillance system, which supplies
      solid basis for recognition and diagnosis of human prion diseases and guarantees
      good quality of China CJD surveillance system.

PMID- 27690735
TI  - Effectiveness of interventions to prevent motorcycle injuries: systematic review
      of the literature.
AB  - Globally, 49% of deaths from traffic crashes occur among vulnerable road users,
      including pedestrians, bicyclists, and motorcyclists. Approximately, a quarter of
      those killed are motorcyclists. The authors carried out a systematic review of
      the literature to evaluate the effectiveness of interventions to prevent
      motorcycle crashes and the associated morbidity and mortality. The studies
      included in this review provide evidence for the effectiveness of helmet use,
      protective clothing, training, and penalties for alcohol consumption and speeding
      in preventing injury and death to motorcyclists. The use of helmets is effective,
      especially if it is universally required by law for drivers and passengers.
      Training to obtain a license also has positive effects but not when it is totally
      voluntary. There is limited but consistent evidence that strengthening laws for
      penalties related to alcohol consumption or speeding has an impact on risk.
      Traffic calming interventions could help reduce crashes in urban areas. In
      jurisdictions where there is limited regulation or adherence to effective
      measures, such as the use of helmets, efforts should be directed primarily at
      expanding such practices. In other areas, efforts can focus on approaches based
      on alternative effective measures or on more innovative interventions adapted to
      local conditions.

PMID- 27690737
TI  - Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits
      to future therapies.
AB  - INTRODUCTION: The mTOR pathway is involved in the regulation of a wide repertoire
      of cellular functions in the brain and its dysregulation is emerging as a
      leitmotif in a large number of neurological disorders. In AD, altered mTOR
      signaling contributes to the inhibition of autophagy deposition of Abeta and tau
      aggregates and to the alteration of several neuronal metabolic pathways. Areas
      covered: In this review, we report all the current findings on the use of mTOR
      inhibitors (rapamycin, rapalogues) in the treatment of AD. These results support
      the role of mTOR inhibitors as potential therapeutic agents able to reduce AD
      hallmarks and recover cognitive performances. Expert commentary: Despite mTOR
      inhibitors appearing to be ideal compounds to counteract AD, further studies are
      needed in order to gain knowledge on the involvement of aberrant mTOR in AD, and
      to standardize a valuable therapeutic approach that can be translated to humans.

PMID- 27690736
TI  - The 3'-untranslated region of mRNAs as a site for ribozyme cleavage-dependent
      processing and control in bacteria.
AB  - Besides its primary informational role, the sequence of the mRNA (mRNA) including
      its 5'- and 3'- untranslated regions (UTRs), contains important features that are
      relevant for post-transcriptional and translational regulation of gene
      expression. In this work a number of bacterial twister motifs are characterized
      both in vitro and in vivo. The analysis of their genetic contexts shows that
      these motifs have the potential of being transcribed as part of polycistronic
      mRNAs, thus we suggest the involvement of bacterial twister motifs in the
      processing of mRNA. Our data show that the ribozyme-mediated cleavage of the
      bacterial 3'-UTR has major effects on gene expression. While the observed effects
      correlate weakly with the kinetic parameters of the ribozymes, they show
      dependence on motif-specific structural features and on mRNA stabilization
      properties of the secondary structures that remain on the 3'-UTR after ribozyme
      cleavage. Using these principles, novel artificial twister-based riboswitches are
      developed that exert their activity via ligand-dependent cleavage of the 3'-UTR
      and the removal of the protective intrinsic terminator. Our results provide
      insights into possible biological functions of these recently discovered and
      widespread catalytic RNA motifs and offer new tools for applications in
      biotechnology, synthetic biology and metabolic engineering.

PMID- 27690738
TI  - The small heat shock protein Hsp31 cooperates with Hsp104 to modulate Sup35 prion
      aggregation.
AB  - The yeast homolog of DJ-1, Hsp31, is a multifunctional protein that is involved
      in several cellular pathways including detoxification of the toxic metabolite
      methylglyoxal and as a protein deglycase. Prior studies ascribed Hsp31 as a
      molecular chaperone that can inhibit alpha-Syn aggregation in vitro and alleviate
      its toxicity in vivo. It was also shown that Hsp31 inhibits Sup35 aggregate
      formation in yeast, however, it is unknown if Hsp31 can modulate [PSI+] phenotype
      and Sup35 prionogenesis. Other small heat shock proteins, Hsp26 and Hsp42 are
      known to be a part of a synergistic proteostasis network that inhibits Sup35
      prion formation and promotes its disaggregation. Here, we establish that Hsp31
      inhibits Sup35 [PSI+] prion formation in collaboration with a well-known
      disaggregase, Hsp104. Hsp31 transiently prevents prion induction but does not
      suppress induction upon prolonged expression of Sup35 indicating that Hsp31 can
      be overcome by larger aggregates. In addition, elevated levels of Hsp31 do not
      cure [PSI+] strains indicating that Hsp31 cannot intervene in a pre-existing
      prion oligomerization cycle. However, Hsp31 can modulate prion status in
      cooperation with Hsp104 because it inhibits Sup35 aggregate formation and
      potentiates [PSI+] prion curing upon overexpression of Hsp104. The absence of
      Hsp31 reduces [PSI+] prion curing by Hsp104 without influencing its ability to
      rescue cellular thermotolerance. Hsp31 did not synergize with Hsp42 to modulate
      the [PSI+] phenotype suggesting that both proteins act on similar stages of the
      prion cycle. We also showed that Hsp31 physically interacts with Hsp104 and
      together they prevent Sup35 prion toxicity to greater extent than if they were
      expressed individually. These results elucidate a mechanism for Hsp31 on prion
      modulation that suggest it acts at a distinct step early in the Sup35 aggregation
      process that is different from Hsp104. This is the first demonstration of the
      modulation of [PSI+] status by the chaperone action of Hsp31. The delineation of
      Hsp31's role in the chaperone cycle has implications for understanding the role
      of the DJ-1 superfamily in controlling misfolded proteins in neurodegenerative
      disease and cancer.

PMID- 27690739
TI  - Neurocognition and inhibitory control in polysubstance use disorders: Comparison
      with alcohol use disorders and changes with abstinence.
AB  - INTRODUCTION: Intact neurocognition and early cognitive recovery during
      abstinence are important for substance use treatment outcome. Yet, little is
      known about them in the largest group of treatment seekers today, individuals
      with polysubstance use disorders (PSU). This study primarily contrasted PSU and
      individuals with an alcohol use disorder (AUD) on neurocognitive and inhibitory
      control measures and, secondarily, measured changes during abstinence in PSU.
      METHOD: At one month of abstinence from all substances except tobacco, 36 PSU and
      69 AUD completed neurocognitive assessments of executive function, general
      intelligence, auditory-verbal learning/memory, visuospatial
      learning/memory/skills, processing speed, working memory, fine motor skills, and
      cognitive efficiency. The groups were also assessed on inhibitory control
      measures of self-reported impulsivity, risk-taking, and decision-making.
      Seventeen PSU repeated the assessments after approximately four months of
      abstinence. All cross-sectional and longitudinal analyses included smoking status
      as a possible confound. RESULTS: At baseline, PSU performed significantly worse
      than AUD on auditory-verbal memory and on an inhibitory control measure of
      impulsivity. Polysubstance users showed trends to worse performance than AUD on
      general intelligence, auditory-verbal learning, and a decision-making task.
      Between one and four months of abstinence, PSU showed significant improvements on
      several neurocognitive and inhibitory control measures. CONCLUSIONS:
      Polysubstance users exhibit distinct differences in neurocognition and inhibitory
      control compared to AUD. Between one and four months of abstinence,
      neurocognition and inhibitory control improve in PSU. This neurocognitive
      recovery in some domains of abstinent PSU is influenced by smoking status. These
      results underscore the clinical value of select methods to augment neurocognitive
      recovery in PSU through appropriate interventions.

PMID- 27690740
TI  - Effect of trait anxiety on cognitive test performance in adolescents with and
      without attention-deficit/hyperactivity disorder.
AB  - INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) and anxiety are
      frequently comorbid disorders associated with different types of abnormal
      performance on neuropsychological tests. Although some studies have shown that
      comorbid anxiety alters ADHD test performance, results inconsistently show both
      improvements and worsening of different abilities, with failures to replicate
      across different anxiety disorders. Alternatively, trait anxiety may reflect a
      more stable influence on ADHD test performance than various diagnosable anxiety
      disorders. METHOD: To better understand the possible enhancing or deleterious
      effects of anxiety on ADHD cognitive impairments, this study examined the effect
      of individual differences in trait anxiety measured by the Multidimensional
      Anxiety Scale for Children (MASC) on a battery of computerized, rapid-performance
      tests measuring attention and impulsivity-related performance in 98 Diagnostic
      and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) Combined
      Subtype ADHD adolescents and 123 healthy controls. It was hypothesized that trait
      anxiety would attenuate response inhibition and attention deficits in ADHD.
      RESULTS: ADHD-diagnosed adolescents with higher trait anxiety performed better on
      indices of sustained attention, reaction time, and motor variability, and had
      altered overall test-performance strategy, while response inhibition was affected
      in both ADHD and non-ADHD. CONCLUSIONS: This study provides the first evidence
      that pathological levels of anxiety are not needed to see differences in ADHD
      neuropsychological test performance. Instead, mildly elevated trait anxiety
      confers a protective influence by reducing the degree of impairment seen in ADHD.
      These findings suggest that better performing ADHD adolescents might have
      optimized levels of cortical arousal, and raise new questions about how best to
      identify the neurobiological substrates responsible for the beneficial effects.

PMID- 27690742
TI  - The impact of administration order in studies of computerized neurocognitive
      assessment tools (NCATs).
AB  - Computerized neurocognitive assessment tools (NCATs) have become a common way to
      assess postconcussion symptoms. As there is increasing research directly
      comparing multiple NCATs to each other, it is important to consider the impact
      that order of test administration may have on the integrity of the results. This
      study investigates the impact of administration order in a study of four
      different NCATs; Automated Neuropsychological Assessment Metrics (ANAM4), CNS
      Vital Signs (CNS-VS), CogState, and Immediate Post-Concussion Assessment and
      Cognitive Test (ImPACT). A total of 272 healthy active duty Service Members were
      enrolled into this study. All participants were randomly assigned to take two of
      the four NCATs with order of administration counterbalanced. Analyses attempted
      to investigate the effect of administration order alone (e.g., Time 1 versus Time
      2), the effect of administration order combined with the impact of the specific
      NCAT received at Time 1, and only the impact of the Time 1 NCAT on Time 2 score
      variability. Specifically, independent samples t tests were used to compare Time
      1 and Time 2 scores within each NCAT. Additional t tests compared Time 1 to Time
      2 scores with Time 2 scores grouped by the NCAT received at Time 1. One-way
      analysis of variance (ANOVA) was used to compare only an NCAT's Time 2 scores
      grouped by the NCAT received at Time 1. Cohen's d effect sizes were calculated
      for all comparisons. The results from this study revealed statistically
      significant order effects for CogState and CNS-VS, though with effect sizes
      generally indicating minimum practical value, and marginal or absent order
      effects for ANAM4 and ImPACT with no clinically meaningful implications. Despite
      finding minimal order effects, clinicians should be mindful of the impact of
      administering multiple NCATs in a single session. Future studies should continue
      to be designed to minimize the potential effect of test administration order.

PMID- 27690743
TI  - Empathising with the enemy: emotion regulation and support for humanitarian aid
      in violent conflicts.
AB  - Considering that negative intergroup emotions can hinder conflict resolution, we
      proposed integrative emotion regulation (IER) as possibly predicting conciliatory
      policies towards outgroups in violent conflict. Two studies examined Jewish
      Israelis' self-reported IER, empathy, liberal attitudes, and support for
      humanitarian aid to Palestinians in Gaza. Study 1 (N = 298) found that unlike
      reappraisal Jewish Israelis' ability to explore emotions (e.g. IER) promoted
      concern for others' emotions (empathy), which in turn predicted support for
      humanitarian aid (while controlling for education level, and religiosity). Study
      2 (N = 291) replicated this mediation model, additionally confirming that liberal
      attitudes (upholding equal, fair treatment for minorities) moderated the relation
      between IER and support for humanitarian aid. Thus, IER linked more strongly with
      humanitarian support when the commitment for liberal egalitarian beliefs was
      high. Preliminary results hold important theoretical and practical implications
      regarding the potential to empathise with outgroup members in intractable
      conflicts.

PMID- 27690744
TI  - RigiScan data under long-term testosterone therapy: improving long-term blood
      circulation of penile arteries, penile length and girth, erectile function, and
      nocturnal penile tumescence and duration.
AB  - BACKGROUND: Late-onset hypogonadism (LOH) presents with low serum testosterone
      (TT) levels and sexual and nonsexual symptoms. Erectile dysfunction affects a
      man's self-esteem and as a result partner relationship and quality of life.
      OBJECTIVES: To investigate the andrological clinical profile outcomes of
      testosterone therapy (TTh) in men (n = 88) with symptomatic LOH complaints and
      symptoms. MAIN OUTCOME MEASURES: Erectile function was assessed using the
      International Index of Erectile Function-5 questionnaire at baseline and at 6 and
      12 months of TTh. In addition, penile length was measured at baseline and 12
      months. We also evaluated nocturnal penile tumescence (NPT, using RigiScan) and
      blood flow of cavernous arteries (penile Doppler ultrasonography) at baseline and
      12 months of TT. MATERIALS AND METHODS: Eighty-eight LOH men (Mage 51.1 years)
      with erectile dysfunction, all with serum TT <10.4 nmol/L before TTh. Patients
      received intramuscular long-acting testosterone undecanoate for 12 months.
      RESULTS: Following TTh, in all patients, serum TT levels were restored within 3
      months to normal levels. Compared with baseline values, erectile function
      significantly improved at 6 (mean score increase 1.95) and 12 months (mean score
      increase 2.16). No significant changes in penile length were observed. NPT
      significantly improved at 12 months in terms of both the frequency (mean increase
      1.27 times) and duration of rigidity (mean increase 5.12 min). As regards the
      blood flow of the cavernous arteries, we observed a significant improvement
      (decrease of 1.16 cm/s) and end diastolic velocity of the penile arteries.
      CONCLUSION: TTh in men with LOH resulted in improvement of the erectile function,
      NPT, and to some extent the blood flow of the cavernous arteries.

PMID- 27690746
TI  - Cognitive risk factors explain the relations between neuroticism and social
      anxiety for males and females.
AB  - The hierarchical model of vulnerabilities to emotional distress contextualizes
      the relation between neuroticism and social anxiety as occurring indirectly
      through cognitive risk factors. In particular, inhibitory intolerance of
      uncertainty (IU; difficulty in uncertain circumstances), fear of negative
      evaluation (FNE; fear of being judged negatively), and anxiety sensitivity (AS)
      social concerns (fear of outwardly observable anxiety) are related to social
      anxiety. It is unclear whether these risk factors uniquely relate to social
      anxiety, and whether they account for the relations between neuroticism and
      social anxiety. The indirect relations between neuroticism and social anxiety
      through these and other risk factors were examined using structural equation
      modeling in a sample of 462 individuals (M age = 36.56, SD = 12.93; 64.3%
      female). Results indicated that the relations between neuroticism and social
      anxiety could be explained through inhibitory IU, FNE, and AS social concerns. No
      gender differences were found. These findings provide support for the
      hierarchical model of vulnerabilities to emotional distress disorders, although
      the cognitive risk factors accounted for variance beyond their contribution to
      the relation between neuroticism and social anxiety, suggesting a more complex
      model than that expressed in the hierarchical model of vulnerabilities.

PMID- 27690745
TI  - Within-session and one-week practice effects on a motor task in amnestic mild
      cognitive impairment.
AB  - Practice effects on neuropsychological tests, which are improvements in test
      scores due to repeated exposure to testing materials, are robust in healthy
      elders, but muted in older adults with cognitive disorders. Conversely, few
      studies have investigated practice effects on motor tasks involving procedural
      memory, particularly across test-retest periods exceeding 24 hours. The current
      study examined one-week practice effects on a novel upper extremity motor task in
      54 older adults with amnestic mild cognitive impairment. Results indicate that
      these individuals with primary memory deficits did improve on this motor task
      within a brief training session as well as across one week. These practice
      effects were unrelated to demographic characteristics or global cognition. One
      week practice effects were, however, negatively related to delayed memory
      function, with larger practice effects being associated with poorer delayed
      memory and potentially better visuospatial ability. The presence of longer term
      practice effects on a procedural motor task not only has implications for how
      longitudinal assessments with similar measures involving implicit memory might be
      interpreted, but may also inform future rehabilitative strategies for patients
      with more severe declarative memory deficits.

PMID- 27690747
TI  - Use of Er:YAG for the treatment of recalcitrant facial verruca plana.
AB  - BACKGROUND: Recalcitrant facial verruca plana (FVP) may persist for years and
      full remission is not always achieved with conventional therapies. The clinical
      success rates reported for different lasers are highly variable and only one
      study evaluated the Er:YAG laser for the treatment of FVP. OBJECTIVE: To
      determine whether Er:YAG is safe and effective for the treatment of recalcitrant
      FVP. METHODS: Forty-six patients with recalcitrant FVP were treated by Er:YAG at
      four-week intervals. The patients' clinical response, adverse effects such as
      scarring and pigment change, recurrence and patient satisfaction were assessed.
      Patients were clinically evaluated after each session over a six-month follow-up.
      RESULTS: A total of 550 lesions of 46 participants were treated with 1-3 passes.
      The patients received 1-4 laser sessions with one session on average. Thirty-two
      patients (62.5%) achieved a complete response with 458 lesions (83.3%) being
      completely and 30 (5.5%) being partially healed. The post-treatment side effects
      were post-inflammatory hyperpigmentation and mild scar formation. FVP recurred in
      12 patients (26.0%). Twenty-six patients (56.5%) were completely satisfied and
      nine (19.5%) were mostly satisfied with the treatment. CONCLUSIONS: Er:YAG laser
      is a good treatment option in patients with recalcitrant FVP, particularly for
      cosmetically sensitive areas.

PMID- 27690748
TI  - Neurological soft signs are associated with attentional dysfunction in children
      with attention deficit hyperactivity disorder.
AB  - INTRODUCTION: Inattention is one of the core symptoms of Attention Deficit
      Hyperactivity Disorder (ADHD). Most of patients with ADHD show motor impairment,
      consisting in the persistence of neurological soft signs (NSS). Our aim was to
      evaluate attentional and motor functioning in an ADHD sample and healthy children
      (HC) and possible link between attentional dysfunction and motor impairment in
      ADHD. METHOD: Twenty-seven drug-naive patients with ADHD and 23 HC were tested
      with a test battery, measuring different aspects of attention. Motor evaluation
      has provided three primary variables: overflow movements (OM), dysrhythmia and
      total speed of timed activities. RESULTS: Compared to HC, patients were impaired
      in a considerable number of attentional processes and showed a greater number of
      NSS. Significant correlations between disturbances of attention and motor
      abnormalities were observed in ADHD group. CONCLUSION: Our findings suggest that
      attentional processes could be involved in the pathophysiology of the NSS and add
      scientific evidence to the predictive value of NSS as indicators of the severity
      of functional impairment in ADHD. Given the marked improvement or complete
      resolution of NSS following treatment with methylphenidate, we suggest that
      evaluation of NSS is useful to monitor the effectiveness of pharmacological
      treatment with MPH in ADHD.

PMID- 27690749
TI  - The effect of core training on distal limb performance during ballistic strike
      manoeuvres.
AB  - Ballistic limb motion is enabled by proximal "core" stiffness. However,
      controversy exists regarding the best method of training this characteristic.
      This study sought to determine the most effective core training method to enhance
      distal limb athleticism. A total of 12 participants (24 +/- 3 years, 1.8 +/- 0.05
      m, 76.8 +/- 9.7 kg) consisting of Muay Thai athletes performed a core training
      protocol (Isometric vs. Dynamic, with Control) for 6 weeks, using a repeated
      measures design to assess performance (peak strike velocity, peak impact force,
      muscular activation) in various strikes. Isometric training increased impact
      force in Jab (554.4 +/- 70.1 N), Cross (1895.2 +/- 203.1 N), Combo (616.8 +/-
      54.9 N), and Knee (1240.0 +/- 89.1 N) trials (P < 0.05). Dynamic training
      increased strike velocity in Jab (1.3 +/- 0.2 m . s-1), Cross (5.5 +/- 0.9 m . s
      1), Combo (0.7 +/- 0.1, 2.8 +/- 0.3 m . s-1), and Knee (3.2 +/- 0.3 m . s-1)
      trials (P < 0.05). Isometric training increased Combo impact force 935.1 +/-
      100.3 N greater than Dynamic and 931.6 +/- 108.5 N more than Control (P < 0.05).
      Dynamic training increased Jab strike velocity 1.3 +/- 0.1 m . s-1 greater than
      Isometric and 0.8 +/- 0.1 m . s-1 more than Control (P < 0.05). It appears that
      both static and dynamic approaches to core training are needed to enhance both
      velocity and force in distal limbs.

PMID- 27690750
TI  - Women's agency and its relationship to current contraceptive use in lower- and
      middle-income countries: A systematic review of the literature.
AB  - Research shows a positive relationship between women's empowerment and
      reproductive health. Yet we know little about the quantitative relationship
      between women's agency and contraceptive use. We conducted a systematic review of
      peer-reviewed literature assessing the link between women's decision-making and
      freedom of movement with their contraceptive use in lower- and middle-income
      countries. Of 102 articles that met the initial screening criteria, 12 met all
      inclusion and exclusion criteria. Of the 12 included studies, consistently
      positive associations with contraceptive use were found in those that measured
      decision-making and freedom of movement as separate constructs. Composite
      measures had a less clear relationship with contraceptive use. In conclusion,
      women's agency is associated with women's contraceptive use in lower- and middle
      income countries. However, the relationship is sensitive to how agency and its
      components are measured. Our review suggests the need for consistent validation
      of scales for women's agency as well as more rigorous research using standardised
      and validated scales, when possible. Longitudinal and intervention studies in
      lower- and middle-income countries will be useful for understanding the causal
      impact of women's agency on contraceptive use, and will help to inform policies
      and programmes to increase contraceptive use in these settings.

PMID- 27690751
TI  - The relationship between sleep and working memory in children with neurological
      conditions.
AB  - The objective of this study is to investigate whether sleep problems might
      account for the increased working memory deficits observed in school-aged
      children with neurological conditions. A novel, transdiagnostic approach to the
      investigation was chosen, and sleep is treated as a process that can potentially
      account for working memory difficulties across a range of neurological
      conditions. Prevalence estimates of sleep problems are also examined. Archival
      data of 237 children aged 6 to 11 years were collected from a Western Australian
      statewide neuropsychological service for the period 26 July 2011 to 14 January
      2014. Measures of parent-reported sleep quality, snoring, and daytime sleepiness
      were obtained, in addition to objective measures of verbal and spatial working
      memory, storage capacity, and processing speed. The results of the data analysis
      reveal that over one third of participants reported having clinically-significant
      levels of sleep problems and that poor sleep quality is significantly associated
      with verbal working memory difficulties. This association remains after
      partialling out the variance contributed to performance by storage capacity and
      processing speed, suggesting that sleep is impacting upon an executive component
      of working memory. No other significant associations are observed. The results
      suggest that poor sleep quality is associated with an executive component of
      verbal (rather than spatial) working memory in children with neurological
      conditions. This has implications for the biological mechanisms thought to
      underlie the relationship between sleep and cognition in children. The results
      also demonstrate the clinical utility of a transdiagnostic approach when
      investigating sleep and cognition in children with neurological conditions.

PMID- 27690741
TI  - Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.
AB  - BACKGROUND: Dupilumab, a human monoclonal antibody against interleukin-4 receptor
      alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines
      that may be important drivers of atopic or allergic diseases such as atopic
      dermatitis. METHODS: In two randomized, placebo-controlled, phase 3 trials of
      identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe
      atopic dermatitis whose disease was inadequately controlled by topical treatment.
      Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks,
      subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab
      every other week alternating with placebo. The primary outcome was the proportion
      of patients who had both a score of 0 or 1 (clear or almost clear) on the
      Investigator's Global Assessment and a reduction of 2 points or more in that
      score from baseline at week 16. RESULTS: We enrolled 671 patients in SOLO 1 and
      708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who
      received dupilumab every other week and in 83 (37%) who received dupilumab
      weekly, as compared with 23 (10%) who received placebo (P<0.001 for both
      comparisons with placebo). The results were similar in SOLO 2, with the primary
      outcome occurring in 84 patients (36%) who received dupilumab every other week
      and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who
      received placebo (P<0.001 for both comparisons). In addition, in the two trials,
      an improvement from baseline to week 16 of at least 75% on the Eczema Area and
      Severity Index was reported in significantly more patients who received each
      regimen of dupilumab than in patients who received placebo (P<0.001 for all
      comparisons). Dupilumab was also associated with improvement in other clinical
      end points, including reduction in pruritus and symptoms of anxiety or depression
      and improvement in quality of life. Injection-site reactions and conjunctivitis
      were more frequent in the dupilumab groups than in the placebo groups.
      CONCLUSIONS: In two phase 3 trials of identical design involving patients with
      atopic dermatitis, dupilumab improved the signs and symptoms of atopic
      dermatitis, including pruritus, symptoms of anxiety and depression, and quality
      of life, as compared with placebo. Trials of longer duration are needed to assess
      the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and
      Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2
      ClinicalTrials.gov number, NCT02277769 .).

PMID- 27690753
TI  - Cytochrome P450 2W1 (CYP2W1) - ready for use as the biomarker and drug target for
      cancer?
AB  - 1. This article aims to evaluate the potentials of using cytochrome P450 2W1
      (CYP2W1) as a biomarker and a drug target of cancer because of its characteristic
      cancer-specific expression. 2. Discrepant findings comparing the expression
      levels of CYP2W1 in cancer and non-cancer samples were reported. In general, the
      expression followed a developmental pattern. The demethylation status of CpG
      island and the expression levels of CYP2W1 genes was positively correlated. 3.
      CYP2W1 was able to activate several procarcinogens, anticancer pro-drugs and to
      metabolise many endogenous substances including fatty acids and
      lysophospholipids. 4. CYP2W1 expression level was suggested to serve as an
      independent prognostic biomarker in colorectal cancer and hepatocellular
      carcinoma. The correlation of genetic polymorphisms of CYP2W1 and cancer risk was
      uncertain. 5. Further characterisation of CYP2W1 structure is suggested to link
      to its functions. More studies are warranted to reveal the true status and the
      regulation of CYP2W1 expression across normal and cancer tissues. Catalytic
      activity of CYP2W1 should be tested on a wider spectrum of endogenous and
      exogenous substances before its use as the drug target. Larger size of clinical
      samples can be included to verify the potential of CYP2W1 as the prognostic or
      cancer risk biomarker.

PMID- 27690752
TI  - Multicomponent analysis of a digital Trail Making Test.
AB  - OBJECTIVE: The purpose of the current study was to use a newly developed digital
      tablet-based variant of the TMT to isolate component cognitive processes
      underlying TMT performance. METHOD: Similar to the paper-based trail making test,
      this digital variant consists of two conditions, Part A and Part B. However, this
      digital version automatically collects additional data to create component
      subtest scores to isolate cognitive abilities. Specifically, in addition to the
      total time to completion and number of errors, the digital Trail Making Test
      (dTMT) records several unique components including the number of pauses, pause
      duration, lifts, lift duration, time inside each circle, and time between
      circles. Participants were community-dwelling older adults who completed a
      neuropsychological evaluation including measures of processing speed, inhibitory
      control, visual working memory/sequencing, and set-switching. The abilities
      underlying TMT performance were assessed through regression analyses of component
      scores from the dTMT with traditional neuropsychological measures. RESULTS:
      Results revealed significant correlations between paper and digital variants of
      Part A (rs = .541, p < .001) and paper and digital versions of Part B (rs = .799,
      p < .001). Regression analyses with traditional neuropsychological measures
      revealed that Part A components were best predicted by speeded processing, while
      inhibitory control and visual/spatial sequencing were predictors of specific
      components of Part B. Exploratory analyses revealed that specific dTMT-B
      components were associated with a performance-based medication management task.
      CONCLUSIONS: Taken together, these results elucidate specific cognitive abilities
      underlying TMT performance, as well as the utility of isolating digital
      components.

PMID- 27690754
TI  - The location of the tibial accelerometer does influence impact acceleration
      parameters during running.
AB  - Tibial accelerations have been associated with a number of running injuries.
      However, studies attaching the tibial accelerometer on the proximal section are
      as numerous as those attaching the accelerometer on the distal section. This
      study aimed to investigate whether accelerometer location influences acceleration
      parameters commonly reported in running literature. To fulfil this purpose, 30
      athletes ran at 2.22, 2.78 and 3.33 m . s-1 with three accelerometers attached
      with double-sided tape and tightened to the participants' tolerance on the
      forehead, the proximal section of the tibia and the distal section of the tibia.
      Time-domain (peak acceleration, shock attenuation) and frequency-domain
      parameters (peak frequency, peak power, signal magnitude and shock attenuation in
      both the low and high frequency ranges) were calculated for each of the tibial
      locations. The distal accelerometer registered greater tibial acceleration peak
      and shock attenuation compared to the proximal accelerometer. With respect to the
      frequency-domain analysis, the distal accelerometer provided greater values of
      all the low-frequency parameters, whereas no difference was observed for the high
      frequency parameters. These findings suggest that the location of the tibial
      accelerometer does influence the acceleration signal parameters, and thus,
      researchers should carefully consider the location they choose to place the
      accelerometer so that equivalent comparisons across studies can be made.

PMID- 27690755
TI  - Steady states and outbreaks of two-phase nonlinear age-structured model of
      population dynamics with discrete time delay.
AB  - In this paper we study the nonlinear age-structured model of a polycyclic two
      phase population dynamics including delayed effect of population density growth
      on the mortality. Both phases are modelled as a system of initial boundary values
      problem for semi-linear transport equation with delay and initial problem for
      nonlinear delay ODE. The obtained system is studied both theoretically and
      numerically. Three different regimes of population dynamics for asymptotically
      stable states of autonomous systems are obtained in numerical experiments for the
      different initial values of population density. The quasi-periodical travelling
      wave solutions are studied numerically for the autonomous system with the
      different values of time delays and for the system with oscillating death rate
      and birth modulus. In both cases it is observed three types of travelling wave
      solutions: harmonic oscillations, pulse sequence and single pulse.

PMID- 27690756
TI  - Resolution of a disputed albendazole result in the UK Official Control System -
      time for more guidance?
AB  - Albendazole, one of the benzimidazole anthelmintics, is used in ruminants and has
      maximum residue limits in muscle, fat and other tissue owing to reported
      teratogenicity. Albendazole is extensively metabolised in domestic animals and
      humans with rapid conversion to a sulphoxide and subsequently sulphone and amino
      sulphone metabolites. Sulphoxide metabolites are responsible for the systemic
      biological activity of benzimidazole drugs. Herein we report a case of disputed
      results for albendazole in a consignment sampled at import in which the Official
      Analyst certified against the consignment for excess albendazole. A laboratory
      acting for the importer reported data below the MRL, including a finding of the
      parent drug which is not included in the residue definition. The Government
      Chemist has a statutory duty as a route of technical appeal in the UK Official
      Food Control system and the case was referred for referee analysis. We report our
      findings based on a LC-MS/MS method, which confirmed the official findings, did
      not reveal the presence of the parent drug but identified hot spots of
      albendazole marker residues in the consignment. We discuss the need for
      recommendations on official sampling at import and interpretation of results.

PMID- 27690757
TI  - Correlates of influenza vaccine uptake among community-dwelling older adults in
      Brazil.
AB  - This study aimed at assessing the factors associated with vaccine uptake in a
      representative sample of community-dwelling Brazilian older adults, specifically
      focusing on differences in socioeconomic factors among the country regions. We
      conducted a cross-sectional, population-based study, using a probabilistic
      household sample in 2013. Individuals aged 60 years or more answered a structured
      questionnaire informing on vaccination status and sociodemographic and behavioral
      covariates. Associations between variables were evaluated using prevalence ratios
      estimated by Poisson regression models. The overall vaccination coverage (72.6%)
      in older adults ranked lower than the goal of 80% stipulated by the Brazilian
      health authority; vaccine uptake differed significantly among the country
      regions. The prevalence of vaccination was lower in black individuals in Brazil
      than that in their white counterparts. The prevalence of vaccine uptake was
      significantly associated with covariates on current life style, use of health
      care, and socioeconomic determinants. Compared with individuals with 0-3 years of
      education, more schooled individuals had higher prevalence of vaccine uptake in
      the North, Northeast, and South regions of the country. This study showed that
      there is room for increasing vaccination coverage among the elderly in Brazil.
      The knowledge previously obtained on factors significantly associated with
      vaccine uptake has not prevented them to continue influencing this outcome. The
      socioeconomic inequality in vaccination in some Brazilian regions reinforces the
      need of targeting the intervention toward the most vulnerable groups.

PMID- 27690758
TI  - An effective self-control strategy for the reduction of aflatoxin M1 content in
      milk and to decrease the exposure of consumers.
AB  - The study reports the results of testing the sensitivity of an early warning
      sampling plan for detecting milk batches with high aflatoxin AFM1 concentration.
      The effectiveness of the method was investigated by the analysis of 9017 milk
      samples collected in Italian milk processing plants that applied control plans
      with different action limits (AL). For those milk processing plants where 30 ng
      kg-1 AL has been applied, the AFM1 contamination was significantly lower at or
      above the 95th percentile of the milk samples when compared with plants that used
      40 ng kg-1 AL. The results show that the control plan can be used effectively for
      early warning of occurrence of high AFM1 contamination of milk and to carry out
      pro-active measures to limit the level of contamination. Estimation of dietary
      exposure was also carried out, based on the aflatoxin M1 content of the milk
      samples and on Italian food consumption data. Estimated Daily Intakes (EDI) and
      Hazard Indices (HI) were calculated for different age groups of the population.
      HIs show that no adverse effects are expected for the adult population, but in
      the case of children under age three, the approximate HI values were considerably
      higher. This underlines the importance of the careful monitoring and control of
      aflatoxin M1 in milk and dairy products.

PMID- 27690759
TI  - Body dissatisfaction in women's artistic gymnastics: A longitudinal study of
      psychosocial indicators.
AB  - Body dissatisfaction is prevalent in women's artistic gymnastics (WAG). Cross
      sectional research points to social and individual risk factors, however it does
      not account for potential changes in body dissatisfaction during an athletic
      season. This study aimed to determine how gymnasts' body dissatisfaction, risk
      factors for eating disorders, media internalisation, perfectionism and mood state
      change during pre-competition, competition and post-competition seasons and to
      identify how these psychosocial indicators impact on body dissatisfaction during
      the athletic year. The sample consisted of 20 Brazilian elite women's artistic
      gymnasts aged 10-16 years. Data were obtained from a 9-month study using: Body
      Shape Questionnaire (BSQ); Eating Attitude Test-26; Sociocultural Attitudes
      Towards Appearance Questionnaire-3 (SATAQ-3); Multidimensional Perfectionism
      Scale (MPS); Brunel Mood Scale (BRUMS) and triceps and subscapular skinfolds.
      Body dissatisfaction was higher during the competition season and disordered
      eating, perfectionism and vigour values were higher in the pre-competition
      season. Disordered eating has been found as the strongest predictor of body
      dissatisfaction during all seasons, and mood state partly contributed to body
      dissatisfaction in the competitive season. Stakeholders should understand that
      body dissatisfaction and the prevalence of disordered eating may change over
      time.

PMID- 27690760
TI  - Residue analysis of thyreostats in baby foods via matrix solid phase dispersion
      and liquid chromatography - dual-polarity electrospray - tandem mass
      spectrometry.
AB  - This paper describes a rapid method for confirming residues of thyreostats in
      meat-based baby foods by using liquid chromatography - dual polarity electrospray
      - tandem mass spectrometry (LC-ES(+/-)-MS/MS). Six thioureylenes, belonging to
      the group of thiouracil and imidazole, were selected for this work: thiouracil
      (TU), methylthiouracil (MTU), propylthiouracil (PTU), phenylthiouracil (PhTU),
      mercaptobenzimidazole (MBI) and tapazole (TAP). The amphoteric nature of these
      compounds allows their electrospray detection in both positive and negative
      ionisation. Nevertheless, MS detection is not favoured by their low molecular
      weights, while their chromatographic retention is also thwarted by their high
      polarity. A pentafluorophenyl (PFP) core-shell phase column was selected to avoid
      peak asymmetry or peak splitting, and a dual-polarity ionisation method was
      optimised to obtain a sensitivity as high as possible. The method was validated
      according to the Commission Decision 657/2002/EC. A simple and fast procedure
      based on matrix solid phase dispersion (MSPD) was optimised to extract analytes
      from baby foods with recoveries exceeding 82%. Limit of decision (CCalpha) and
      detection capability (CCbeta) were lower than the permissible maximum
      concentration (10 ng g-1). The validated method was then applied to assess the
      potential occurrence of the six selected thyreostats in nine commercial products.
      All the samples were found free of contamination.

PMID- 27690761
TI  - The effect of natural and built environmental characteristics on pedestrian
      vehicle crash severity in Ghana.
AB  - Despite the benefits of walking as a means of travelling, walking can be quite
      hazardous. Pedestrian-vehicle crashes remain a major concern in Ghana as they
      account for the highest percentage of fatalities. The objective of this study is
      to determine the effect of both natural and built environmental features on
      pedestrian-vehicle crash severity in Ghana. The study is based on an extensive
      pedestrian-vehicle crash dataset extracted from the National Road Traffic
      Accident Database at the Building and Road Research Institute (BRRI) of the
      Council for Scientific and Industrial Research (CSIR), Ghana. Using a multinomial
      logit modelling framework, possible determinants of pedestrian-vehicle crash
      severity were identified. The study found that fatal crashes are likely to occur
      during unclear weather conditions, on weekends, at night time where there are no
      lights, on curved and inclined roads, on untarred roads, at mid-blocks and on
      wider roads. The developed model and its interpretations will make important
      contributions to road crash analysis and prevention in Ghana with the possibility
      of extension to other developing countries. These contributing factors could
      inform policy makers on road design and operational improvements.

PMID- 27690764
TI  - Editorial: Final Musings on the Impact of Molecular Endocrinology.

PMID- 27690766
TI  - Editorial: Reflections on the Impact of Molecular Endocrinology on a Scientific
      Career.

PMID- 27690765
TI  - Reflections on the Merger of Molecular Endocrinology and Endocrinology.

PMID- 27690767
TI  - Editorial: Centennial Celebration - An Interview With Professor Evan Simpson on
      Hormones and Cancer.

PMID- 27690768
TI  - Bidding a Fond Farwell to Molecular Endocrinology.

PMID- 27690769
TI  - Origins of the Field of Molecular Endocrinology: A Personal Perspective.

PMID- 27690762
TI  - Immunogenicity of AS03-adjuvanted and non-adjuvanted trivalent inactivated
      influenza vaccines in elderly adults: A Phase 3, randomized trial and post-hoc
      correlate of protection analysis.
AB  - In this study we describe the immunogenicity results from a subset of older
      people (N = 5187) who participated in a Phase 3 randomized, observer-blinded
      trial of AS03-TIV versus TIV (FluarixTM) (ClinicalTrials.gov, NCT00753272).
      Participants received one dose of AS03-TIV or TIV in each study year and antibody
      titers against the vaccine strains were assessed using hemagglutination
      inhibition (HI) assay at 21 d and 180 d post-vaccination in each vaccine group in
      the 2008/09 (Year 1) and 2009/10 (Year 2) influenza seasons. Manufacturing
      consistency of 3 lots of AS03-TIV for HI antibody responses in Year 1 was a co
      primary objective. In a post-hoc analysis, a statistical regression model
      included 4830 subjects in whom immunogenicity and laboratory-confirmed attack
      rate data were available; the analysis was performed to assess HI antibody titers
      against A/H3N2 as a correlate of protection for laboratory-confirmed A/H3N2
      influenza. AS03-TIV and TIV elicited strong HI antibody responses against each
      vaccine strain 21 d post-vaccination in both years. The manufacturing consistency
      of 3 lots of AS03-TIV was demonstrated. In both years and each vaccine group, HI
      antibody responses were lower for A/H1N1 than the other vaccine strains. Day 180
      seroconversion rates (proportion with >=4-fold increase in titer compared with
      pre-vaccination titer) in Year 1 in the AS03-TIV and TIV groups, respectively,
      were 87.7% and 74.1% for A/H3N2, 69.7% and 59.6% for influenza B, and 58.3% and
      47.4% for A/H1N1. The post-hoc statistical model based on A/H3N2 attack rates and
      HI antibody titers estimated that a 4-fold increase in post-vaccination titers
      against A/H3N2 was associated with a 2-fold decrease in the odds of A/H3N2
      infection.

PMID- 27690770
TI  - Editorial Reflections on the Demise of Molecular Endocrinology and the Future of
      Molecular Hormone Action Research.

PMID- 27690831
TI  - Quercetin attenuates neuronal autophagy and apoptosis in rat traumatic brain
      injury model via activation of PI3K/Akt signaling pathway.
AB  - OBJECTIVE: Neuronal autophagy and apoptosis play an irreplaceable role in brain
      injury pathogenesis and may represent a hopeful target for treatment. Previous
      studies have demonstrated that administration of quercetin-attenuated brain
      damage in a variety of brain injury models including traumatic brain injury
      (TBI). However, whether PI3K/Akt signaling pathway mediates the neuroprotection
      of quercetin following TBI is not well clarified. We sought to propose a
      hypothesis that quercetin could attenuate neuronal autophagy and apoptosis via
      enhancing PI3K/Akt signaling. METHODS: All rats were randomly arranged into four
      groups as follows: sham group (n = 25), TBI group (n = 25), TBI + quercetin group
      (n = 25), TBI + quercetin + LY294002 group (n = 25). Quercetin (Sigma, USA,
      dissolved in 0.9% saline solution) was administered intraperitoneally at a dose
      of 50 mg/kg at 30 min, 12 h, and 24 h after TBI. The neurological impairment and
      spatial cognitive function was assessed by the neurologic severity score and
      Morris water maze, respectively. Immunohistochemistry staining and western
      blotting was used to evaluate the expression of LC3, p-Akt, caspase-3, Bcl-2, and
      Bax. RESULTS: Quercetin treatment significantly attenuated TBI-induced
      neurological impairment (1-3 days, p < 0.05) and improved cognitive function (5-8
      days, p < 0.05). Double immunolabeling demonstrated that quercetin significantly
      reduced the LC3-positive cells co-labeled with NeuN, whereas significantly
      enhanced p-Akt-positive cells co-labeled with NeuN. Furthermore, quercetin
      treatment reduced the expression of LC3,caspase-3 and Bax levels induced
      following TBI (p < 0.05), and increased the expression of p-Akt and Bcl-2 at 48 h
      (p < 0.05). CONCLUSION: In conclusion, our observations indicate that post-injury
      treatment with quercetin could inhibit neuronal autophagy and apoptosis in the
      hippocampus in a rat model of TBI. The neuroprotective effects of quercetin may
      be related to modulation of PI3K/Akt signaling pathway.

PMID- 27690832
TI  - Intraoral extraction of an ectopic mandibular third molar detected in the
      subcondylar region without a pathological cause: A case report and literature
      review.
AB  - PURPOSE: To present a case report on the presence of an ectopic mandibular third
      molar (EMTM), the surgical treatment, and outcome. CASE REPORT: A 63-year-old
      woman presented with right preauricular facial swelling, limited jaw function,
      and pain. Radiographic assessment demonstrated an EMTM positioned in the
      superoposterior aspect of the ramus. Radiographically, there was a bony tunnel
      extending from the third molar to distal of the second molar. The patient was
      treated by an intraoral approach on the medial aspect of the ramus for removal of
      the ectopic third molar, as well as the tissue in the bony tunnel. RESULTS: The
      patient healed uneventfully. The soft tissue in the bony canal was granulation
      tissue, and nerve function was preserved. A literature search of EMTMs was
      conducted identifying 17 reported cases. CONCLUSION: Three-dimensional imaging in
      the management of EMTM can be beneficial in identifying position of the tooth,
      associated pathology, and identifying the position of neurovascular structures to
      aid in removal of the ectopic tooth.

PMID- 27690833
TI  - Unstable Os Odontoideum.
AB  - A 24-year-old male Marine presented to a direct-access physical therapy clinic
      with a chief complaint of bilateral hand paresthesia secondary to a parachuting
      accident when his neck was forced into lateral flexion. Due to the positive
      neurologic findings and history of trauma, the physical therapist ordered
      cervical spine imaging. The odontoid was not adequately visualized on
      radiographs, but computed tomography revealed an os odontoideum. J Orthop Sports
      Phys Ther 2016;46(10):930. doi:10.2519/jospt.2016.0417.

PMID- 27690834
TI  - Whiplash Injury or Concussion? A Possible Biomechanical Explanation for
      Concussion Symptoms in Some Individuals Following a Rear-End Collision.
AB  - Study Design Finite element modeling of experimental data. Background The
      clinical presentations of whiplash injury and concussion have considerable
      overlap. Both diagnoses are generally based on presenting signs and symptoms, and
      a history of neck or head trauma. With incomplete knowledge of the trauma,
      differentiating between whiplash injury and concussion can be clinically
      challenging. Objectives To estimate the brain strains that develop during rear
      end car crashes, evaluate how these strains vary with different head kinematic
      parameters, and compare these strains to those generated during potentially
      concussive football helmet impacts. Methods Head kinematic data were analyzed
      from 2 prior studies, one that focused on head restraint impacts in rear-end
      crash tests and another that focused on football helmet impacts. These data were
      used as inputs to a finite element model of the human brain. Brain strains were
      calculated and compared to different peak kinematic parameters and between the 2
      impact conditions. Results Brain strains correlated best with the head's angular
      velocity change for both impact conditions. The 4 crashes with head angular
      velocity changes greater than 30 rad/s (greater than 1719 degrees /s) generated
      the highest brain stains. One crash, in which the head wrapped onto the top of
      the head restraint, generated brain strains similar to a 9.3-m/s rear football
      helmet impact, a level previously associated with concussion. Conclusion This
      work provides new insight into a potential biomechanical link between whiplash
      injury and concussion, and advances our understanding of how head restraint
      interaction during a rear-end crash may cause an injury more typically associated
      with sports-related head impacts. J Orthop Sports Phys Ther 2016;46(10):874-885.
      doi:10.2519/jospt.2016.7049.

PMID- 27690835
TI  - MicroRNA 320a Predicts Chronic Axial and Widespread Pain Development Following
      Motor Vehicle Collision in a Stress-Dependent Manner.
AB  - Study Design Prospective human cohort study combined with molecular studies.
      Background A microRNA is a small, noncoding RNA molecule that can play a role in
      disease onset. Recent studies found that circulating levels of microRNA 320a (miR
      320a) are associated with musculoskeletal pain conditions and that miR-320a is
      stress responsive. Objectives To investigate whether circulating expression
      levels of miR-320a in the peritraumatic period predict persistent axial
      musculoskeletal pain 6 months after motor vehicle collision (MVC). Methods We
      evaluated whether (1) circulating miR-320a and related members of the miR-320a
      family predict axial musculoskeletal pain and other musculoskeletal pain outcomes
      6 months following MVC, and (2) miR-320a regulates stress system and pain-related
      transcripts in cell culture. Given the wealth of data suggesting that biological
      mechanisms influencing pain outcomes are often sex and/or stress dependent,
      interactions between miR-320a, stress, and sex were evaluated. Results In primary
      analyses (n = 69), a significant crossover interaction was observed between the
      influence of circulating miR-320a and peritraumatic distress (beta = -0.01, P =
      .002) on post-MVC axial musculoskeletal pain. Reduced peritraumatic miR-320a
      expression levels predicted axial musculoskeletal pain in distressed individuals
      (beta = -0.12, P = .006) but not nondistressed individuals. In secondary
      analyses, miR-320a predicted widespread musculoskeletal pain, and related members
      of the miR-320a family also predicted axial and widespread musculoskeletal pain.
      In cell culture, miR-320a bound stress and pain-associated 3'UTR transcripts
      (FKBP5, ADCYAP1, PER2, and NR3C1). Conclusion These data suggest that miR-320a
      may help mediate regional and widespread changes in pain sensitivity after MVC. J
      Orthop Sports Phys Ther 2016;46(10):911-919. doi:10.2519/jospt.2016.6944.

PMID- 27690836
TI  - Advancements in Imaging Technology: Do They (or Will They) Equate to Advancements
      in Our Knowledge of Recovery in Whiplash?
AB  - Synopsis It is generally accepted that up to 50% of those with a whiplash injury
      following a motor vehicle collision will fail to fully recover. Twenty-five
      percent of these patients will demonstrate a markedly complex clinical picture
      that includes severe pain-related disability, sensory and motor disturbances, and
      psychological distress. A number of psychosocial factors have shown prognostic
      value for recovery following whiplash from a motor vehicle collision. To date, no
      management approach (eg, physical therapies, education, psychological
      interventions, or interdisciplinary strategies) for acute whiplash has positively
      influenced recovery rates. For many of the probable pathoanatomical lesions (eg,
      fracture, ligamentous rupture, disc injury), there remains a lack of available
      clinical tests for identifying their presence. Fractures, particularly at the
      craniovertebral and cervicothoracic junctions, may be radiographically occult.
      While high-resolution computed tomography scans can detect fractures, there
      remains a lack of prevalence data for fractures in this population. Conventional
      magnetic resonance imaging has not consistently revealed lesions in patients with
      acute or chronic whiplash, a "failure" that may be due to limitations in the
      resolution of available devices and the use of standard sequences. The
      technological evolution of imaging techniques and sequences eventually might
      provide greater resolution to reveal currently elusive anatomical lesions (or,
      perhaps more importantly, temporal changes in physiological responses to assumed
      lesions) in those patients at risk of poor recovery. Preliminary findings from 2
      prospective cohort studies in 2 different countries suggest that this is so, as
      evidenced by changes to the structure of skeletal muscles in those who do not
      fully recover. In this clinical commentary, we will briefly introduce the
      available imaging decision rules and the current knowledge underlying the
      pathomechanics and pathophysiology of whiplash. We will then acknowledge known
      prognostic factors underlying functional recovery. Last, we will highlight
      emerging evidence regarding the pathobiology of muscle degeneration/regeneration,
      as well as advancements in neuroimaging and musculoskeletal imaging techniques
      (eg, functional magnetic resonance imaging, magnetization transfer imaging,
      spectroscopy, diffusion-weighted imaging) that may be used as noninvasive and
      objective complements to known prognostic factors associated with whiplash
      recovery, in particular, poor functional recovery. J Orthop Sports Phys Ther
      2016;46(10):861-872. doi:10.2519/jospt.2016.6735.

PMID- 27690837
TI  - Cervical Spine Fracture With Vertebral Artery Dissection.
AB  - A 51-year-old man presented to a direct-access physical therapy clinic with
      persistent neck pain for 5 days after a fall in shallow water while surfing.
      Based on "dangerous mechanism of injury" from the Canadian cervical spine rule as
      being a high risk factor, the physical therapist ordered radiographs of the
      cervical spine, which were suggestive of a more serious injury. Computed
      tomography suggested and magnetic resonance imaging confirmed vertebral artery
      dissection. J Orthop Sports Phys Ther 2016;46(10):929.
      doi:10.2519/jospt.2016.0416.

PMID- 27690838
TI  - Whiplash-Associated Disorders: Occupant Kinematics and Neck Morphology.
AB  - Synopsis Despite considerable research effort, the incidence of whiplash injury
      during automotive collisions has continued to rise. This is due, at least in
      part, to a limited recognition of biomechanical injury mechanisms and factors
      influencing injury risk. While automotive safety modifications reduced injury
      risk in some cases, impact on the overall whiplash incidence was limited. This is
      likely attributable to significant occupant-related differences that have a
      profound impact on injury risk. Many of those differences were outlined in
      research studies, and examples include female sex and the associated sex-based
      anthropometrical variation that can affect seating orientation; cervical spinal
      posture; and anatomical attributes, including cervical column slenderness and
      neck muscle morphometry. This review highlights these anatomical attributes and
      explains, based on biomechanical concepts, the method by which these attributes
      may alter cervical spine response during automotive rear impacts to affect injury
      risk. The biomechanical explanations are based on existing studies that have
      incorporated postmortem human subjects, computational models, and anthropomorphic
      test devices (ie, crash test dummies), as well as medical imaging in human
      volunteers. These biomechanical explanations may provide improved understanding
      of injury risk. J Orthop Sports Phys Ther 2016;46(10):834-844.
      doi:10.2519/jospt.2016.6846.

PMID- 27690839
TI  - Preventable Injuries/Fatalities Due to Distracted Driving: A Call for a
      Coordinated Action.
AB  - In the past decade, distracted driving has emerged as one of the most prominent
      global road safety concerns. The singular and combined efforts of many
      organizations, such as Drop It And Drive (DIAD) and the Traffic Injury Research
      Foundation (TIRF), have identified the need for partnerships, shared information,
      and access to interpretable research findings to guide decision making and to
      identify effective strategies to reduce, if not eliminate, preventable
      injuries/fatalities from distracted driving, including whiplash-associated
      disorders. This editorial describes activities in 5 target areas identified in
      our environmental scan in Canada: (1) provincial/territorial government
      strategies, (2) enforcement, (3) data collection and measurement, (4) awareness
      campaigns, and (5) legislation. We will also reinforce the potential benefits of
      seeking and establishing meaningful interdisciplinary partnerships to reduce
      distracted driving across the globe. Finally, this editorial provides an example
      of how these interdisciplinary partnerships can help reduce preventable, life
      altering injuries/deaths caused by distracted driving. J Orthop Sports Phys Ther
      2016;46(10):818-821. doi:10.2519/jospt.2016.0113.

PMID- 27690840
TI  - Whiplash Continues Its Challenge.
AB  - There have been many advances in the management of neck pain disorders, but a
      personal frustration as a clinician and researcher in the field is that the
      incidence of full recovery following a whiplash injury as a result of a motor
      vehicle crash has not increased and, subsequently, the rate of transition to
      chronic neck pain has not lessened. The commentaries in this special issue
      reflect the multifaceted nature of whiplash-associated disorders and the wide
      ranging research in the field. While management of whiplash, especially the
      challenge of lessening the rate of transition to chronicity, has yet to be
      achieved, the picture is becoming clearer. This should give great confidence and
      some hope to individuals with whiplash-associated disorders who have long-term
      pain and functional disability that after the next decade of research and
      clinical development, the outcomes following whiplash are likely to be vastly
      improved. J Orthop Sports Phys Ther 2016;46(10):815-817.
      doi:10.2519/jospt.2016.0112.

PMID- 27690841
TI  - Assessment and Management of Whiplash From the Emergency and Acute Care Setting:
      Care, Questions, and Future Global Research Needs.
AB  - The primary goal of this editorial is to discuss the care patients typically
      receive in the immediate post-motor vehicle collision setting and the questions
      patients typically ask with respect to their symptoms and prognosis. Commentary
      and guidance are provided from the perspective of an acute care physician on what
      we should be able to tell patients and providers going forward. J Orthop Sports
      Phys Ther 2016;46(10):822-825. doi:10.2519/jospt.2016.0114.

PMID- 27690843
TI  - Corrigendum.

PMID- 27690842
TI  - Distinction of clenbuterol intake from drug or contaminated food of animal origin
      in a controlled administration trial - the potential of enantiomeric separation
      for doping control analysis.
AB  - The differentiation of clenbuterol abuse and unintentional ingestion from
      contaminated meat is crucial with respect to the valuation of an adverse
      analytical finding in human sports doping control. The proportion of the two
      enantiomers of clenbuterol may serve as potential discriminating parameter. For
      the determination of the individual enantiomers, specific methods were developed
      and validated for the different matrices under investigation based on chiral
      chromatography coupled to tandem mass spectrometry. Data are presented from the
      administration to humans of clenbuterol from a pharmaceutical preparation, and
      from cattle meat and liver containing residues. A shift in the proportion of the
      enantiomers in cattle meat is detected and this signature is also found in human
      urine after ingestion. Thus, an altered enantiomeric composition of clenbuterol
      may be used to substantiate athletes' claims following adverse analytical
      findings in doping control. However, in meat, the enantiomeric composition was
      found to be highly variable. Species as well as tissue dependent variances need
      to be considered in interpreting enantiomer discrimination. Analysis of post
      administration urines from a controlled experiment comparing the administration
      of racemic clenbuterol from a registered pharmaceutical preparation and the
      administration of residue-containing meat and liver (nonracemic mixture) from
      treated animals is reported. Furthermore doping control samples from Mexican U17
      World Championship 2011 of the Federation Internationale de Football Association
      (FIFA), with adverse analytical findings for clenbuterol, were re-analysed.

PMID- 27691050
TI  - Probing the interaction of thionine with human serum albumin by
      multispectroscopic studies and its in vitro cytotoxic activity toward MCF-7
      breast cancer cells.
AB  - The studies on protein-dye interactions are important in biological process and
      it is regarded as vital step in rational drug design. The interaction of thionine
      (TH) with human serum albumin (HSA) was analyzed using isothermal titration
      calorimetry (ITC), spectroscopic, and molecular docking technique. The emission
      spectral titration of HSA with TH revealed the formation of HSA-TH complex via
      static quenching process. The results obtained from absorption, synchronous
      emission, circular dichroism, and three-dimensional (3D) emission spectral
      studies demonstrated that TH induces changes in the microenvironment and
      secondary structure of HSA. Results from ITC experiments suggested that the
      binding of TH dye was favored by negative enthalpy and a favorable entropy
      contribution. Site marker competitive binding experiments revealed that the
      binding site of TH was located in subdomain IIA (Sudlow site I) of HSA. Molecular
      docking study further substantiates that TH binds to the hydrophobic cavity of
      subdomain IIA (Sudlow site I) of HSA. Further, we have studied the cytotoxic
      activity of TH and TH-HSA complex on breast cancer cell lines (MCF-7) by MTT
      assay and LDH assay. These studies revealed that TH-HSA complex showed the higher
      level of cytotoxicity in cancer cells than TH dye-treated MCF-7 cells and the
      significant adverse effect did not found in the normal HBL-100 cells.
      Fluorescence microscopy analyses of nuclear fragmentation studies validate the
      significant reduction of viability of TH-HSA-treated human MCF-7 breast cancer
      cells through activation of apoptotic-mediated pathways.

PMID- 27691051
TI  - Career Advancement: Meeting the Challenges Confronting the Next Generation of
      Endocrinologists and Endocrine Researchers.
AB  - CONTEXT: Challenges and opportunities face the next generation (Next-Gen) of
      endocrine researchers and clinicians, the lifeblood of the field of endocrinology
      for the future. A symposium jointly sponsored by The Endocrine Society and the
      Endocrine Society of Australia was convened to discuss approaches to addressing
      the present and future Next-Gen needs. EVIDENCE ACQUISITION: Data collection by
      literature review, assessment of previously completed questionnaires,
      commissioning of a new questionnaire, and summarization of symposium discussions
      were studied. EVIDENCE SYNTHESIS: Next-Gen endocrine researchers face diminishing
      grant funding in inflation-adjusted terms. The average age of individuals being
      awarded their first independent investigator funding has increased to age 45
      years. For clinicians, a workforce gap exists between endocrinologists needed and
      those currently trained. Clinicians in practice are increasingly becoming
      employees of integrated hospital systems, resulting in greater time spent on
      nonclinical issues. Workforce data and published reviews identify challenges
      specifically related to early career women in endocrinology. Strategies to
      Address Issues: Recommendations encompassed the areas of grant support for
      research, mentoring, education, templates for career development, specific
      programs for Next-Gen members by senior colleagues as outlined in the text,
      networking, team science, and life/work integration. Endocrine societies focusing
      on Next-Gen members provide a powerful mechanism to support these critical areas.
      CONCLUSIONS: A concerted effort to empower, train, and support the next
      generation of clinical endocrinologists and endocrine researchers is necessary to
      ensure the viability and vibrancy of our discipline and to optimize our
      contributions to improving health outcomes. Collaborative engagement of endocrine
      societies globally will be necessary to support our next generation moving
      forward.

PMID- 27691052
TI  - mTOR Inhibitors for the Treatment of Severe Congenital Hyperinsulinism:
      Perspectives on Limited Therapeutic Success.
AB  - CONTEXT: Congenital hyperinsulinism (CHI) is the most common cause of persistent
      hypoglycemia in neonates and infants. In medically unresponsive CHI, subtotal
      pancreatectomy is performed to achieve euglycemia with consequent diabetes in
      later life. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been
      reported to obviate the need for pancreatectomy, but experience is limited.
      OBJECTIVE: We have investigated the efficacy and adverse effect profile of mTOR
      inhibitors in the treatment of severe CHI. DESIGN, SETTING, AND PATIENTS: This
      was an observational review of 10 severe CHI patients treated with mTOR
      inhibitors, in France and the United Kingdom, with the intention of achieving
      glycemic control without pancreatectomy. Safety information was recorded. MAIN
      OUTCOME MEASURE(S): We examined whether mTOR inhibitors achieved glycemic
      control, fasting tolerance, and weaning of supportive medical therapy. RESULTS:
      mTOR inhibition achieved euglycemia, fasting tolerance, and reduced medical
      therapy in only three patients (30%). Triglyceride levels were elevated in five
      patients (50%). One child required a blood transfusion for anemia, four had
      stomatitis, two had sepsis, one developed varicella zoster, and two patients
      developed gut dysmotility in association with exocrine pancreatic insufficiency.
      In silico analysis of transcriptome arrays from CHI patients revealed no
      significant association between mTOR signaling and disease. Pancreatic tissue
      from two patients who did not respond to sirolimus showed no reduction in cell
      proliferation, further suggesting that mTOR signaling did not down-regulate
      proliferation in the CHI pancreas. CONCLUSION: mTOR inhibitor treatment is
      associated with very limited success and must be used with caution in children
      with severe CHI.

PMID- 27691373
TI  - Psychological factors influence the gastroesophageal reflux disease (GERD) and
      their effect on quality of life among firefighters in South Korea.
AB  - OBJECTIVES: The purpose of this study was to examine psychosocial factors related
      to gastroesophageal reflux disease (GERD) and their effects on quality of life
      (QOL) in firefighters. METHODS: Data were collected from 1217 firefighters in a
      Korean province. We measured psychological symptoms using the scale. In order to
      observe the influence of the high-risk group on occupational stress, we conduct
      logistic multiple linear regression. The correlation between psychological
      factors and QOL was also analyzed and performed a hierarchical regression
      analysis. RESULTS: GERD was observed in 32.2% of subjects. Subjects with GERD
      showed higher depressive symptom, anxiety and occupational stress scores, and
      lower self-esteem and QOL scores relative to those observed in GERD - negative
      subject. GERD risk was higher for the following occupational stress
      subcategories: job demand, lack of reward, interpersonal conflict, and
      occupational climate. The stepwise regression analysis showed that depressive
      symptoms, occupational stress, self-esteem, and anxiety were the best predictors
      of QOL. CONCLUSIONS: The results suggest that psychological and medical
      approaches should be combined in GERD assessment.

PMID- 27691374
TI  - State-to-State Variation in SSI Enrollment for Children With Mental Disabilities:
      An Administrative and Ethical Challenge.
AB  - OBJECTIVE: The study examined state variation in rates of Supplemental Security
      Income (SSI) determinations, allowances, and receipt of benefits for ten selected
      child mental disabilities in 2013. METHODS: SSI administrative and U.S. Census
      Bureau data collected by a multidisciplinary consensus committee convened by the
      National Academies of Science, Engineering, and Medicine in 2015 were examined.
      RESULTS: Less than 1% of children in 2013 were recipients of SSI for mental
      disabilities. Determination rates ranged from 1,441 to 251 per 100,000 low-income
      children, an almost sixfold difference. Allowance rates varied from 16% to 78%, a
      fivefold difference. Receipt of benefits ranged from .7% to 5.3%, a sevenfold
      difference. CONCLUSIONS: Large unexplained discrepancies across states were found
      in review and receipt of SSI benefits for low-income children with mental
      disabilities. Inequities that cannot be explained by disability severity or
      financial need violate the ethos of equitable access to federally entitled
      services.

PMID- 27691375
TI  - Utilization and Cost of Health Care Services During the First Episode of
      Psychosis.
AB  - OBJECTIVE: Because of the chronicity, severity, and marked psychosocial
      impairment that may characterize the illness, schizophrenia is an incredibly
      costly disease. Recent data indicate that intervention earlier in the course of
      schizophrenia produces cost savings. This study compared health service
      utilization and associated costs for patients receiving treatment for first
      episode psychosis (FEP) delivered within the early-intervention (EI) model at the
      Prevention and Recovery Center for Early Psychosis (PARC) and for a matched
      sample of FEP patients receiving treatment as usual at a geographically similar
      mental health clinic. METHODS: This study was a retrospective assessment of 76
      PARC patients and 75 patients receiving treatment as usual who were matched by
      age, race, sex, and diagnosis. Clinical and health service utilization data were
      extracted from the Midtown and Regenstrief Medical Record Systems, and
      differences between demographic variables, health service utilization, and cost
      of services were compared. RESULTS: Although individuals at PARC had higher
      physician and nurse visit costs, these were offset by a decrease in costs for
      acute service utilization. The PARC cohort did not show any difference from the
      comparison group in terms of total outpatient clinic services used and had fewer
      inpatient, psychiatric crisis, and emergency room services. Cost analyses
      reflected a total estimated savings of just over $6,900 per patient. CONCLUSIONS:
      These findings indicate not only that EI results in cost savings but that
      increasing medical services may be key in reducing the use of acute services,
      presumably because of a reduction in psychiatric and general medical pathology.

PMID- 27691377
TI  - Ethics of Coercive Treatment and Misuse of Psychiatry.
AB  - The author discusses a pragmatic approach to decisions about coercive treatment
      that is based on four principles from principle-based ethics: respect for
      autonomy, nonmaleficence, beneficence, and justice. This approach can reconcile
      psychiatry's perspective with the U.N. Convention on the Rights of Persons With
      Disabilities. Coercive treatment can be justified only when a patient's capacity
      to consent is substantially impaired and severe danger to health or life cannot
      be prevented by less intrusive means. In this case, withholding treatment can
      violate the principle of justice. In the case of danger to others, social
      exclusion and loss of freedom can be seen as harming psychosocial health, which
      can justify coercive treatment. Considerable efforts are required to support
      patients' informed decisions and avoid allowing others to make substitute
      decisions. Mental disorder alone without impaired capacity does not justify
      involuntary treatment, which can be considered a misuse of psychiatry.
      Involuntary detention without treatment can be justified for short periods for
      assessment and to offer treatment options.

PMID- 27691376
TI  - Collaborative Care for Perinatal Depression Among Socioeconomically Disadvantaged
      Women: Adverse Neonatal Birth Events and Treatment Response.
AB  - OBJECTIVE: The study examined the effectiveness of a perinatal collaborative care
      intervention in moderating the effects of adverse neonatal birth events on risks
      of postpartum depressive symptoms and impaired functioning among women of lower
      socioeconomic status with antenatal depression. METHODS: A randomized controlled
      trial with blinded outcome assessments was conducted in ten public health
      centers, comparing MOMCare (choice of brief interpersonal psychotherapy,
      pharmacotherapy, or both) with intensive maternity support services (MSS-Plus).
      Participants had probable diagnoses of major depressive disorder or dysthymia
      during pregnancy. Generalized estimating equations estimated differences in
      depression and functioning measures between groups with and without adverse birth
      events within the treatment arms. A total of 160 women, 43% of whom experienced
      at least one adverse birth event, were included in the analyses. RESULTS: For
      women who received MOMCare, postpartum depression scores (measured with the
      Symptom Checklist-20) did not differ by whether or not they experienced an
      adverse birth event (mean+/-SD scores of .86+/-.51 for mothers with an adverse
      birth event and .83+/-.56 for mothers with no event; p=.78). For women who
      received MSS-Plus, having an adverse birth event was associated with persisting
      depression in the postpartum period (mean scores of 1.20+/-.0.61 for mothers with
      an adverse birth event and .93+/-.52 for mothers without adverse birth event;
      p=.04). Similar results were seen for depression response rates and functioning.
      CONCLUSIONS: MOMCare mitigated the risk of postpartum depressive symptoms and
      impaired functioning among women of low socioeconomic status who had antenatal
      depression and who experienced adverse birth events.

PMID- 27691378
TI  - Antidepressant Medication Prescribing Practices for Treatment of Major Depressive
      Disorder.
AB  - OBJECTIVE: The purpose of this study was to describe the prescribing practices of
      clinicians for patients with major depressive disorder (MDD). METHODS: This
      population-based, descriptive study of insured patients (N=54,107) identified
      people who were 18 years or older, had a claim for MDD, had at least one
      prescription for an antidepressant medication in 2013, and had continuous
      insurance coverage during the study period. Prescription claims were evaluated to
      determine the most commonly prescribed antidepressant medication and most common
      dose. RESULTS: The three most commonly prescribed antidepressant medications were
      citalopram (N=11,995, 22.2%), sertraline (N=10,791, 19.9%), and trazodone
      (N=9,501, 17.6%). The most common daily doses were 20 mg citalopram (N=6,304,
      52.6%), 50 mg sertraline (N=4,173, 38.7%), and 100 mg trazodone (N=3,220, 33.9%).
      CONCLUSIONS: This is the first report of its kind that provides drug- and dosage
      level details to demonstrate that antidepressant prescribing in clinical practice
      is largely within recommended guidelines.

PMID- 27691379
TI  - The Connecticut Mental Health Center: Celebrating 50 Years of a Successful
      Partnership Between the State and Yale University.
AB  - September 28, 2016, marked the 50th anniversary of the Connecticut Mental Health
      Center, a state-owned and state-operated joint venture between the state and Yale
      University built and sustained with federal, state, and university funds.
      Collaboration across these entities has produced a wide array of clinical,
      educational, and research initiatives, a few of which are described in this
      column. The missions of clinical care, research, and education remain the
      foundation for an organization that serves 5,000 individuals each year who are
      poor and who experience serious mental illnesses and substance use disorders.

PMID- 27691380
TI  - The Humble Leader: Association of Discrepancies in Leader and Follower Ratings of
      Implementation Leadership With Organizational Climate in Mental Health.
AB  - OBJECTIVES: Discrepancies, or perceptual distance, between leaders' self-ratings
      and followers' ratings of the leader are common but usually go unrecognized.
      Research on discrepancies is limited, but there is evidence that discrepancies
      are associated with organizational context. This study examined the association
      of leader-follower discrepancies in Implementation Leadership Scale (ILS) ratings
      of mental health clinic leaders and the association of those discrepancies with
      organizational climate for involvement and performance feedback. Both involvement
      and performance feedback are important for evidence-based practice (EBP)
      implementation in mental health. METHODS: A total of 593 individuals-supervisors
      (leaders, N=80) and clinical service providers (followers, N=513)-completed
      surveys that included ratings of implementation leadership and organizational
      climate. Polynomial regression and response surface analyses were conducted to
      examine the associations of discrepancies in leader-follower ILS ratings with
      organizational involvement climate and performance feedback climate, aspects of
      climate likely to support EBP implementation. RESULTS: Both involvement climate
      and performance feedback climate were highest where leaders rated themselves low
      on the ILS and their followers rated those leaders high on the ILS ("humble
      leaders"). CONCLUSIONS: Teams with "humble leaders" showed more positive
      organizational climate for involvement and for performance feedback, contextual
      factors important during EBP implementation and sustainment. Discrepancy in
      leader and follower ratings of implementation leadership should be a
      consideration in understanding and improving leadership and organizational
      climate for mental health services and for EBP implementation and sustainment in
      mental health and other allied health settings.

PMID- 27691381
TI  - Assessing Telemedicine Utilization by Using Medicaid Claims Data.
AB  - OBJECTIVE: This study characterized telemedicine utilization among Medicaid
      enrollees by patients' demographic characteristics, geographic location,
      enrollment type, eligibility category, and clinical conditions. METHODS: This
      study used 2008-2009 Medicaid claims data from 28 states and the District of
      Columbia to characterize telemedicine claims (indicated by GT for professional
      fee claims or Q3014 for facility fees) on the basis of patients' demographic
      characteristics, geographic location, enrollment type, eligibility category, and
      clinical condition as indicated by ICD-9 codes. States lacking Medicaid
      telemedicine reimbursement policies were excluded. Chi-square tests were used to
      compare telemedicine utilization rates and one-way analysis of variance was used
      to estimate mean differences in number of telemedicine encounters among
      subgroups. RESULTS: A total of 45,233,602 Medicaid enrollees from the 22 states
      with telemedicine reimbursement policies were included in the study, and .1% were
      telemedicine users. Individuals ages 45 to 64 (16.4%), whites (11.3%), males
      (8.5%), rural residents (26.0%), those with managed care plans (7.9%), and those
      categorized as aged, blind, and disabled (28.1%) were more likely to receive
      telemedicine (p<.001). Nearly 95% of telemedicine claims were associated with a
      behavioral health diagnosis, of which over 50% were for bipolar disorder and
      attention-deficit disorder or attention-deficit hyperactivity disorder (29.3% and
      23.4%, respectively). State-level variation was high, ranging from .0 to 59.91
      claims per 10,000 enrollees (Arkansas and Arizona, respectively). CONCLUSIONS:
      Despite the touted potential for telemedicine to improve health care access,
      actual utilization of telemedicine in Medicaid programs was low. It was
      predominantly used to treat behavioral health diagnoses. Reimbursement alone is
      insufficient to support broad utilization for Medicaid enrollees.

PMID- 27691387
TI  - News & Notes.

PMID- 27691388
TI  - Opening More Doors to End Homelessness Through a Shared Housing Approach.

PMID- 27691382
TI  - Qualitative Analysis of Resources and Barriers Related to Treatment of Borderline
      Personality Disorder in the United States.
AB  - OBJECTIVE: Resources and treatment for individuals with borderline personality
      disorder (BPD) are limited and often difficult to obtain. This article aimed to
      identify key resources for and barriers to obtaining supportive and treatment
      services for BPD from the perspective of individuals seeking information or
      services related to BPD ("BPD care seekers"). METHODS: Data came from transcripts
      of resource requests to the Borderline Personality Disorder Resource Center from
      January 2008 to December 2015 (N=6,253). Basic statistics, including the type of
      service requested, demographic information for the BPD care seeker, and national
      distribution of requests, were generated for all eligible transcripts.
      Qualitative analysis of a random subset of 500 transcripts was used to identify
      themes, challenges, and common experiences reported by BPD care seekers. RESULTS:
      The greatest number of requests for primary services or resources among the
      random subset of transcripts was for outpatient services (51%), informational
      materials (13%), and day programs (9%). Family services, crisis intervention, and
      mental health literacy were identified as areas where available resources did not
      meet current demand and that could be improved or expanded. Factors identified as
      potential barriers to finding and obtaining appropriate treatment for BPD
      included stigmatization and marginalization within mental health care systems,
      financial concerns, and comorbidity with psychiatric or medical disorders.
      CONCLUSIONS: BPD care seekers face numerous barriers to obtaining appropriate
      care. Expanded services and resources to connect individuals with treatment are
      needed to meet the current demands and preferences of those seeking care.

PMID- 27691390
TI  - Folie a Trois: Prescribers', Pharmacists', and Patients' Shared Delusion of
      Medication Reconciliation.

PMID- 27691391
TI  - Electronic Psychiatric Consultation in Primary Care in the Safety Net.

PMID- 27691392
TI  - Work Is Integral to Mental Health.

PMID- 27691398
TI  - Preparation and characterization of polyelectrolyte complex nanoparticles based
      on poly (malic acid), chitosan. A pH-dependent delivery system.
AB  - The main objective of this work was to develop polyelectrolyte complex (PEC)
      nanoparticles based on poly (malic acid), chitosan (PMLA/CS) as pH-dependent
      delivery systems. The results indicated that the PMLA/CS Nps were successfully
      prepared. The prepared PMLA/CS Nps showed spherical morphology with a mean
      diameter of 212.81 nm and negative surface charge of -24.60 mV, and revealing
      significant pH-sensitive properties as the mass ratio of PMLA to CS was 5:5. The
      prepared PMLA/CS Nps were characterized by FT-IR, TEM and DLS. The prepared
      PMLA/CS Nps remained stable over a temperature range of 4-53  degrees C.
      Doxorubicin (Dox) as a model drug was loaded on the nanoparticles through the
      physical adsorption method. The high drug loading efficiency (16.9%) and the
      sustained release patterns in acidic media were observed, and the release
      accelerated in alkaline solutions. MTT based cytotoxic analysis also depicted the
      non-toxic nature of PMLA/CS Nps, while Dox-PMLA/CS Nps showed dose-dependent
      cytotoxicity towards MDA-MB-231 cells. Hence, the nanoparticles could be
      potentially applied as pH sensitive drug vehicles for controlled release.

PMID- 27691399
TI  - Affinity enhancement of nanobody binding to EGFR: in silico site-directed
      mutagenesis and molecular dynamics simulation approaches.
AB  - Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein, is
      overexpressed in many cancers such as head-neck, breast, prostate, and skin
      cancers for this reason it is a good target in cancer therapy and diagnosis. In
      nanobody-based cancer diagnosis and treatment, nanobodies with high affinity
      toward receptor (e.g. EGFR) results in effective treatment or diagnosis of
      cancer. In this regard, the main aim of this study is to develop a method based
      on molecular dynamic (MD) simulations for designing of 7D12 based nanobody with
      high affinity compared with wild-type nanobody. By surveying electrostatic and
      desolvation interactions between different residues of 7D12 and EGFR, the
      critical residues of 7D12 that play the main role in the binding of 7D12 to EGFR
      were elucidated and based on these residues, five logical variants were designed.
      Following the 50 ns MD simulations, pull and umbrella sampling simulation were
      performed for 7D12 and all its variants in complex with EGFR. Binding free energy
      of 7D12 (and all its variants) with EGFR was obtained by weighted histogram
      analysis method. According to binding free energy results, GLY101 to GLU mutation
      showed the highest binding affinity but this variant is unstable after 50 ns MD
      simulations. ALA100 to GLU mutation shows suitable binding enhancement with
      acceptable structural stability. Suitable position and orientation of GLU in
      residue 100 of 7D12 against related amino acids of EGFR formed some extra
      hydrogen and electrostatic interactions which resulted in binding enhancement.

PMID- 27691453
TI  - Study of positive and negative plasma catalytic oxidation of ethylene.
AB  - The effect of introducing a photocatalytically active coating inside a plasma
      unit is investigated. This technique combines the advantages of high product
      selectivity from catalysis and the fast start-up from plasma technology. In this
      study, a preselected TiO2 coating is applied on the collector electrode of a DC
      corona discharge unit as non-thermal plasma reactor, in order to study the
      oxidation of ethylene. For both positive and negative polarities an enhanced
      mineralization is observed while the formation of by-products drastically
      decreases. The plasma catalytic unit gave the best results when using negative
      polarity at a voltage of 15 kV. This shows the potential of plasma catalysis as
      indoor air purification technology.

PMID- 27691454
TI  - Force- and power-time curve comparison during jumping between strength-matched
      male and female basketball players.
AB  - The purpose of this study was to compare force- and power-time curve variables
      during jumping between Division I strength-matched male and female basketball
      athletes. Males (n = 8) and females (n = 8) were strength matched by testing a
      one-repetition maximum (1RM) back squat. 1RM back squat values were normalised to
      body mass in order to demonstrate that strength differences were a function of
      body mass alone. Subjects performed three countermovement jumps (CMJ) at maximal
      effort. Absolute and relative force- and power-time curve variables from the CMJs
      were analysed between males and females. Average force- and power-time curves
      were generated for all subjects. Jump height was significantly greater (p <= .05)
      in males than females. Absolute force was higher in males during the concentric
      phase, but not significantly different (p >= .05) when normalised to body mass.
      Significance was found in absolute concentric impulse between sexes, but not when
      analysed relative to body mass. Rate of force development, rate of power
      development, relative peak force, and work were not significantly different
      between sexes. Males had significantly greater impulse during the eccentric phase
      as well as peak power (PP) during the concentric phase of the CMJ than did
      females in both absolute and relative terms. It is concluded that sex differences
      are not a determining factor in measured force during a CMJ when normalised to
      body mass between strength-matched subjects. However, eccentric phase impulse and
      concentric phase PP appear to be influenced by sex differences independent of
      matching strength levels.

PMID- 27691601
TI  - Methoxy poly (ethylene glycol)-b-poly (delta-valerolactone) copolymeric micelles
      for improved skin delivery of ketoconazole.
AB  - Ketoconazole is a broad spectrum imidazole antifungal drug. For the treatment of
      superficial fungal infections with ketoconazole, it needs to be permeated to deep
      skin layers. In order to develop topical formulation of ketoconazole for
      improving its skin deposition and water-solubility, ketoconazole-loaded methoxy
      poly (ethylene glycol)-b-poly (delta-valerolactone) micelles were developed
      through thin-film hydration method. Particle size, drug loading capacity,
      infrared spectrum and X-ray diffraction of drug-loaded micelles were
      characterized. The optimal drug formulation was selected for skin delivery and
      deposition investigation performed by use of mice skin, and its in vitro release
      and antifungal activity were also investigated. Penetration and distribution in
      the skin were also visualized using fluorescein-loaded micelles and fluorescence
      microscopy. The drug-loaded micelles were obtained with encapsulation efficiency
      of 86.39% and particle diameter of about 12 nm. The micelles made ketoconazole
      aqueous solubility increase to 86-fold higher than crude one. Ketoconazole-loaded
      micelles showed no skin permeation of ketoconazole, obviously enhance skin
      deposition and demonstrated similar antifungal activity as compared with marketed
      ketoconazole cream. Fluorescein-loaded micelles displayed higher skin deposition
      than fluorescein water solution. These results demonstrate that the MPEG-PVL
      micelle is a potential delivery system for ketoconazole in the field of skin
      delivery.

PMID- 27691659
TI  - Synthesis of monodisperse core shell PVA@P(AMPS-co-NIPAm) nanogels structured for
      pre-concentration of Fe(III) ions.
AB  - Core shell-structured poly(vinyl alcohol) @ poly(2-acrylamido-2-methyl-1-propane
      sulfonic acid-co-N-isopropylacrylamide) PVA@P(AMPS-co-NIPAm) spheres are
      synthesized. The well-defined PVA@P(AMPS-co-NIPAm) core shell nanogels with
      diameter nearly 30 nm enriches Fe(III), and the nanogels are characterized by FT
      IR, TEM, SEM and X-ray diffraction (XRD). The many factors affecting adsorption
      were successfully investigated. The maximum capacity of Fe(III) ions was 320
      (mg/g) for PVA@P(90AMPS-co-10NIPAm) (wt.: wt%). The equilibrium data matching
      well with the Langmuir model and the pseudo-second-order form described the
      adsorption process better than the pseudo-first-order model. Findings of the
      present study highlight using a simple synthesis of PVA@P(AMPS-co-NIPAm) nanogels
      as superior and recyclable nanoadsorbents.

PMID- 27691718
TI  - Reduction of excess sludge in a sequencing batch reactor by lysis-cryptic growth
      using quick lime for disintegration under low temperature.
AB  - In the present study, quick-lime-based thermal-alkaline sludge disintegration
      (SD) under low temperature was combined with cryptic growth to investigate the
      excess sludge reduction efficiency in the sequencing batch reactor (SBR). The
      optimized condition of SD was as follows: T = 80C, pH = 11, t = 180 min, and the
      SD rate was about 42.1%. With 65.6% of excess sludge disintegrated and returned
      to the SBR, the system achieved sludge reduction rate of about 40.1%. The lysis
      cryptic growth still obtained satisfactory sludge reduction efficiency despite
      the comparative low SD rate, which suggested that disintegration rate might not
      be the decisive factor for cryptic-growth-based sludge reduction. Lysis-cryptic
      growth did not impact the effluent quality, yet the phosphorus removal
      performance was enhanced, with effluent total phosphorus concentration decreased
      by 0.3 mg/L (33%). Crystal compounds of calcium phosphate precipitate were
      detected in the system by Fourier transform infrared spectroscopy and X-ray
      diffraction, which indicated the phosphorus removal potential of SD using lime.
      Moreover, endogenous dehydrogenase activity of activated sludge in the lysis
      cryptic system was enhanced, which was beneficial for sludge reduction. SD and
      cryptic growth in the present study demonstrates an economical and effective
      approach for sludge reduction.

PMID- 27691719
TI  - The (oxalato)aluminate complex as an antimicrobial substance protecting the
      "shiro" of Tricholoma matsutake from soil micro-organisms.
AB  - Tricholoma matsutake, a basidiomycete, forms ectomycorrhizas with Pinus
      densiflora as the host tree. Its fruiting body, "matsutake" in Japanese, is an
      edible and highly prized mushroom, and it grows in a circle called a fairy ring.
      Beneath the fairy ring of T. matsutake, a whitish mycelium-soil aggregated zone,
      called "shiro" in Japanese, develops. The front of the shiro, an active
      mycorrhizal zone, functions to gather nutrients from the soil and roots to
      nourish the fairy ring. Bacteria and sporulating fungi decrease from the shiro
      front, whereas they increase inside and outside the shiro front. Ohara
      demonstrated that the shiro front exhibited antimicrobial activity, but the
      antimicrobial substance has remained unidentified for 50 years. We have
      identified the antimicrobial substance as the (oxalato)aluminate complex, known
      as a reaction product of oxalic acid and aluminum phosphate to release soluble
      phosphorus. The complex protects the shiro from micro-organisms, and contributes
      to its development.

PMID- 27691720
TI  - Effect of seven Indian plant extracts on Fenton reaction-mediated damage to DNA
      constituents.
AB  - The influences of substoichiometric amounts of seven plant extracts in the Fenton
      reaction-mediated damage to deoxynucleosides, deoxynucleoside monophosphates,
      deoxynucleoside triphosphates, and supercoiled plasmid DNA were studied to
      rationalize anticancer properties reported in some of these extracts. Extracts
      from Acacia catechu, Emblica officinalis, Spondias dulcis, Terminalia belerica,
      Terminalia chebula, as well as gallic acid, epicatechin, chebulagic acid and
      chebulinic acid enhance the extent of damage in Fenton reactions with all
      monomeric substrates but protect supercoiled plasmid DNA, compared to standard
      Fenton reactions. The damage to pyrimidine nucleosides/nucleotides is enhanced by
      these extracts and compounds to a greater extent than for purine ones in a
      concentration dependent manner. Dolichos biflorus and Hemidesmus indicus extracts
      generally do not show this enhancement for the monomeric substrates though they
      protect plasmid DNA. Compared to standard Fenton reactions for deoxynucleosides
      with ethanol, the presence of these five plant extracts render ethanol scavenging
      less effective as the radical is generated in the vicinity of the target. Since
      substoichiometric amounts of these extracts and the four compounds produce this
      effect, a catalytic mechanism involving the presence of a ternary complex of the
      nucleoside/nucleotide substrate, a plant compound and the hydroxyl radical is
      proposed. Such a mechanism cannot operate for plasmid DNA as the planar rings in
      the extract compounds cannot stack with the duplex DNA bases. These plant
      extracts, by enhancing Fenton reaction-mediated damage to deoxynucleoside
      triphosphates, slow down DNA replication in rapidly dividing cancer cells, thus
      contributing to their anticancer properties.

PMID- 27691721
TI  - Sensitivity, reliability and the effects of diurnal variation on a test battery
      of field usable upper limb fatigue measures.
AB  - Fatigue has been linked to deficits in production quality and productivity and,
      if of long duration, work-related musculoskeletal disorders. It may thus be a
      useful risk indicator and design and evaluation tool. However, there is limited
      information on the test-retest reliability, the sensitivity and the effects of
      diurnal fluctuation on field usable fatigue measures. This study reports on an
      evaluation of 11 measurement tools and their 14 parameters. Eight measures were
      found to have test-retest ICC values greater than 0.8. Four measures were
      particularly responsive during an intermittent fatiguing condition. However, two
      responsive measures demonstrated rhythmic behaviour, with significant time
      effects from 08:00 to mid-afternoon and early evening. Action tremor, muscle
      mechanomyography and perceived fatigue were found to be most reliable and most
      responsive; but additional analytical considerations might be required when
      interpreting daylong responses of MMG and action tremor. Practitioner Summary:
      This paper presents findings from test-retest and daylong reliability and
      responsiveness evaluations of 11 fatigue measures. This paper suggests that
      action tremor, muscle mechanomyography and perceived fatigue were most reliable
      and most responsive. However, mechanomyography and action tremor may be
      susceptible to diurnal changes.

PMID- 27691776
TI  - Current Status of Home Medical Care Waste Collection by Nurses in Japan.
AB  - : A questionnaire survey was conducted to determine the current status of home
      medical care (HMC) waste collection by nurses for individual items and whether
      the collection rate differs with city size. The questionnaire was mailed to 1,022
      nursing offices, of which 645 offices provided valid responses. Offices were
      classified into three groups according to the local population size. Responses
      indicated that used syringes and needles, except for pen-type self-injection
      needles, were collected by >50% of HMC nurses. On the other hand, enteral
      nutrients, nutritional adjustment diet vessels, feeding tubes, portable
      injectors, ventilator masks, endotracheal suction catheters, tracheal cannulas,
      continuous ambulatory peritoneal dialysis (CAPD) bags, and urinary catheters and
      bags had a low collection rate in comparison with syringes or needles. The
      collection percentage of used syringes, needles, and infusion needles (p < 0.05)
      and that for infusion bags, tubes, and catheters (p < 0.001) differed among the
      three population groups. Although municipalities are responsible for collect all
      HMC waste, sharp or infectious items should be collected by HMC doctors or
      nurses. On the contrary, nonhazardous HMC waste should be collected by
      municipalities. IMPLICATIONS: This paper illustrates the status of waste
      collection of individual home medical care (HMC) items by HMC nurses. Infectious
      waste, such as needles and syringes, is collected by nurses. The collection rate
      of infectious waste by nurses in large cities was low compared with that in small
      cities. Although municipalities are responsible for collecting all HMC waste,
      sharp or infectious items should be collected by HMC doctors or nurses, whereas
      nonhazardous HMC waste should be collected by the municipalities.

PMID- 27691777
TI  - Remembering Robert Geary.

PMID- 27691778
TI  - Gallbladder incisional hernia: CT findings with surgical correlation.

PMID- 27691779
TI  - Understanding How Policy and Culture Create Oppressive Conditions for LGBTQ2S
      Youth in the Shelter System.
AB  - This study examined the experiences that lesbian, gay, bisexual, transgender,
      queer, questioning, and two-spirit (LGBTQ2S) homeless youth have in shelters and
      the disjunctures that occur for this population in Toronto's shelter system. The
      attitudes and behaviors of shelter workers and management toward LGBTQ2S youth
      were also explored. A critical action research approach, informed by critical
      ethnography and institutional ethnography was employed. Thirty-three people
      participated in this study in the Greater Toronto Area. The study triangulated
      data from interviews, focus groups, observations, and document analysis. The
      systemic enactment of homophobia, transphobia, and hegemonic masculinity are
      often normalized in shelters and create significant barriers to safe, accessible,
      and supportive services for LGBTQ2S youth. Excessive bureaucratic regulation and
      the lack of necessary bureaucratic regulation in highly significant areas play a
      key role in creating the disjunctures that occur for LGBTQ2S youth in shelters.

PMID- 27691780
TI  - Torsion of a mesenchymal hamartoma of the liver in a 1-year-old boy.
AB  - We report a case of a one-year-old boy who was referred to our clinic suspected
      of having acute abdomen. On physical examination, the abdomen was soft, diffusely
      tender with weak peristalsis. Ultrasonography and MRI of the right hemiabdomen
      demonstrated a well-defined, solid, expansive formation with slightly lobulated
      contours and an interspersed inhomogeneous structure with overall dimensions of
      59 * 45 * 50 mm. After midline laparotomy was performed, a cystic tumor was
      found, twisted around a pedicle which was arising from the falciform ligament and
      it measured 5-6 cm in diameter. The tumor appeared to be necrotic. The mass was
      ligated and extirpated on the pedicle and sent for histopathological analysis.
      After the surgery, the boy was hemodynamically stable, without respiratory
      complications and all laboratory findings were within normal limits.
      Histopathological analysis showed that the tumor was composed of mesenchymal
      stroma with sparse glimpses of hepatocytes and bile ducts with partly cystic
      changes lined by orderly epithelium. Given the clinical data, histology and
      immunohistochemistry analysis (alpha-fetoprotein, CK8/18, hepatocyte, desmin and
      CD31) a diagnosis of a twisted mesenchymal hamartoma of the liver was made.

PMID- 27691783
TI  - Exploring stereochemical specificity of phosphotriesterase by MM-PBSA and MM-GBSA
      calculation and steered molecular dynamics simulation.
AB  - Wild-type phosphotriesterase (PTE) prefers the SP-enantiomers over the
      corresponding RP-enantiomers by factors ranging from 10 to 90. To satisfy the
      binding modes of the PTE of SP- and RP-enantiomers, all-atom molecular dynamics
      simulations were carried out on two paraoxon SP and RP derivatives, namely, Sp-1
      and Rp-1. Molecular mechanics Poisson-Boltzmann surface area and molecular
      mechanics generalized Born surface area (MM-PBSA and MM-GBSA) calculations
      indicated that His230 in Sp-1-PTE had a closer interaction with the substrate
      than that in Rp-1-PTE and that such interaction increased the catalytic
      efficiency of PTE for Sp-1. The steered molecular dynamics simulation indicated
      that, compared with Sp-1, Rp-1 in the unbinding (binding) may hinder some residue
      displacement, thus requiring more effort to escape the binding pocket of PTE. In
      addition, Trp131, Phe306, and Tyr309 are deemed important residues for the Sp-1
      unbinding pathway via PTE, whereas Tyr309 alone is considered an important
      residue for the Rp-1 unbinding pathway. These results demonstrate the possibility
      of dramatically altering the stereoselectivity and overall reactivity of the
      native enzyme toward chiral substrates by modifying specific residues located
      within the active site of PTE.

PMID- 27691840
TI  - Is Gaydar Affected by Attitudes Toward Homosexuality? Confidence, Labeling Bias,
      and Accuracy.
AB  - Previous research has largely ignored the relationship between sexual orientation
      judgement accuracy, confidence, and attitudes toward homosexuality. In an online
      study, participants (N = 269) judged the sexual orientation of homosexual and
      heterosexual targets presented via a series of facial photographs. Participants
      also indicated their confidence in each judgment and completed the Modern
      Homonegativity Scale (Morrison & Morrison, 2002). We found that (1) homosexual
      men and heterosexual women were more accurate when judging photographs of women
      as opposed to photographs of men, and (2) in heterosexual men, negative attitudes
      toward homosexual men predicted confidence and bias when rating men's
      photographs. Findings indicate that homosexual men and heterosexual women are
      similar in terms of accuracy in judging women's sexuality. Further, especially in
      men, homophobia is associated with cognitive biases in labeling other men but
      does not have a relationship with increased accuracy.

PMID- 27691784
TI  - Personal value preferences, group identifications, and cultural practices of
      Palestinian Israelis working in close contact with Jewish Israelis.
AB  - The present study investigates the connection between personal value preferences,
      group identifications, and cultural practices among Palestinian Israelis working
      in close contact with the Jewish population in Israel. One hundred twenty-two
      Palestinian Israelis participated in the study. The participants were employed in
      different professional positions in the Tel Aviv Metropolitan area and were
      recruited to the study using the snowball technique. A stronger national
      identification was associated with a higher preference for the security and
      conformity values, and a lower preference for the humility values. A stronger
      ethnic identification was associated with a lower preference for the security,
      power, and stimulation values. Group identifications mediated the connection
      between personal value preferences and cultural practices. A longer time working
      in close contact with the majority group and less frequent visits home were
      associated with a greater adherence to the majority group's cultural practices
      but not with adherence to the ethnic group's practices and not with the group
      identifications.

PMID- 27691841
TI  - Contribution of 2-methyl-3-furanthiol to the cooked meat-like aroma of fermented
      soy sauce.
AB  - The cooked meat-like aroma compound, 2-methyl-3-furanthiol (2M3F), was detected
      in fermented soy sauce (FSS) by GC-olfactometry and GC-MS. 2M3F was present in
      FSS at a concentration considerably greater than the perception threshold, and
      the 2M3F concentration increased with heating temperature. Sensory analysis
      indicated that with the addition of only 0.2 MUg/L of 2M3F to the soy sauce
      sample, the cooked meat-like aroma is significantly stronger than that of sample
      without the addition of 2M3F. Hence, 2M3F contributes to the cooked meat-like
      aroma of FSS, which constitutes the key aroma component of FSS. In addition, 2M3F
      was generated from the addition of ribose and cysteine in FSS by heating at 120 
      degrees C, but it was not detected in a phosphate buffer under the same
      condition. Furthermore, 2M3F was not detected in acid-hydrolyzed vegetable
      protein-mixed soy sauce (ASS) and heated ASS. These results indicated that
      fermentation by micro-organisms facilitates the generation of 2M3F in FSS.

PMID- 27691842
TI  - Design of novel lead molecules against RhoG protein as cancer target - a
      computational study.
AB  - Cancer is a class of diseases characterized by uncontrolled cell growth. Every
      year more than 2 million people are affected by the disease. Rho family proteins
      are actively involved in cytoskeleton regulation. Over-expression of Rho family
      proteins show oncogenic activity and promote cancer progression. In the present
      work RhoG protein is considered as novel target of cancer. It is a member of Rho
      family and Rac subfamily protein, which plays pivotal role in regulation of
      microtubule formation, cell migration and contributes in cancer progression. In
      order to understand the binding interaction between RhoG protein and the DH
      domain of Ephexin-4 protein, the 3D structure of RhoG was evaluated and Molecular
      Dynamic Simulations was performed to stabilize the structure. The 3D structure of
      RhoG protein was validated and active site identified using standard
      computational protocols. Protein-protein docking of RhoG with Ephexin-4 was done
      to understand binding interactions and the active site structure. Virtual
      screening was carried out with ligand databases against the active site of RhoG
      protein. The efficiency of virtual screening is analysed with enrichment factor
      and area under curve values. The binding free energy of docked complexes was
      calculated using prime MM-GBSA module. The SASA, FOSA, FISA, PISA and PSA values
      of ligands were carried out. New ligands with high docking score, glide energy
      and acceptable ADME properties were prioritized as potential inhibitors of RhoG
      protein.

PMID- 27691903
TI  - Association between possible sleep bruxism and sleep characteristics in children.
AB  - AIMS: To evaluate the relationship between possible sleep bruxism and sleep
      characteristics in children. METHODOLOGY: A cross-sectional study was conducted
      through data collection of a pre-tested questionnaire answered by 111 parents on
      behalf of their children in the waiting room during their appointment at the
      Pediatric Dentistry Clinic of a public Brazilian university. The diagnosis of
      possible sleep bruxism was based on the international classification of sleep
      disorders (ICSD) criteria. The Chi-square test and logistic multinomial
      regression test were used in the statistical analysis. RESULTS: The final model
      of logistic multinomial regression demonstrated that children with muscle pain in
      the mouth region (OR = 19.70 95% IC = 1.82-212.69), snoring (OR = 8.25 95% IC =
      2, 56-26, 54), and those with parents with possible sleep bruxism have more of a
      probability of sleep bruxism. CONCLUSION: Potential sleep bruxism tends to be
      hereditary. Muscle pain, snoring, and mouth breathing were important signals
      associated with possible sleep bruxism among children.

PMID- 27691904
TI  - Pharmacokinetics and estimated bioavailability of grapiprant, a novel selective
      prostaglandin E2 receptor antagonist, after oral administration in fasted and fed
      dogs.
AB  - AIMS: To assess the effect of food intake on the pharmacokinetics of grapiprant
      administered orally at 2 mg/kg, and to estimate its oral bioavailability in dogs.
      METHODS: Eight healthy female Labrador Retriever dogs, aged 4-10 years were used.
      In the initial trial two dogs were administered a 0.5 mg/kg I/V bolus of
      grapiprant dissolved in ethanol. In the second trial, six dogs were assigned to
      two treatment groups, using a randomised cross-over design, and received 2 mg/kg
      of grapiprant orally, as pure powder, after fasting for 12 hours or after being
      fed. Blood samples were collected at preassigned times up to 36 hours after
      administration, and concentrations of grapiprant in plasma determined using
      validated high performance liquid chromatography. RESULTS: After I/V
      administration in the two dogs the terminal half life was 5.30 and 6.06 hours,
      clearance was 444 and 476 mL/hours/kg, and volume of distribution was 3,642 and
      3,883 mL/kg. Compared with fasted dogs, oral administration in fed dogs resulted
      in reduced median peak concentrations in plasma (1,598 vs. 614 ng/mL) and delayed
      median time of peak concentration (1.0 vs. 3.0 hours). The estimated
      bioavailability in fasted and fed dogs was 111.9 and 59.1%, respectively.
      Concentrations of grapiprant in plasma following oral administration, in either
      fed or fasted dogs, remained higher than 164 ng/mL for up to 6 hours. This
      concentration has been estimated to be the minimal effective concentration
      required to control pain in dogs. CONCLUSION AND RELEVANCE: Oral administration
      of 2 mg/kg grapiprant in fed and fasted dogs resulted in different
      pharmacokinetics of the drug, but did not influence the length of time when
      concentrations in plasma exceeded theoretical effective concentrations. Further
      studies are necessary to verify these findings using pharmacokinetic
      pharmacodynamic studies and in clinical subjects.

PMID- 27691905
TI  - Genome shuffling of Lactobacillus plantarum C88 improves adhesion.
AB  - Genome shuffling is an important method for rapid improvement in microbial
      strains for desired phenotypes. In this study, ultraviolet irradiation and
      nitrosoguanidine were used as mutagens to enhance the adhesion of the wild-type
      Lactobacillus plantarum C88. Four strains with better property were screened
      after mutagenesis to develop a library of parent strains for three rounds of
      genome shuffling. Fusants F3-1, F3-2, F3-3, and F3-4 were screened as the
      improved strains. The in vivo and in vitro tests results indicated that the
      population after three rounds of genome shuffling exhibited improved adhesive
      property. Random Amplified Polymorphic DNA results showed significant differences
      between the parent strain and recombinant strains at DNA level. These results
      suggest that the adhesive property of L. plantarum C88 can be significantly
      improved by genome shuffling. Improvement in the adhesive property of bacterial
      cells by genome shuffling enhances the colonization of probiotic strains which
      further benefits to exist probiotic function.

PMID- 27691906
TI  - Skeletal deformities associated with nutritional congenital rickets in newborn
      lambs.
AB  - CASE HISTORY: A group of 545 pregnant rising 2-year-old Coopdale ewes on a
      Southland sheep farm were grazed over winter on a fodder beet (Beta vulgaris)
      crop. Subsequently, 45 out of approximately 750 lambs were born with a variety of
      skeletal deformities, including shortened limbs, varus and valgus angular limb
      deformities, palmar grade stance and cranial bowing of the carpus. Analysis of
      the crop showed the fodder beet contained a low percentage of phosphorus. In
      addition, 60 out of 460 rising 2-year-old ewes that had been grazed on the fodder
      beet crop as 1-year-olds had incisor abnormalities and malocclusion. PATHOLOGICAL
      FINDINGS: Two affected lambs (1-day-old and 3-days-old) with representative
      clinical signs examined postmortem were found to have markedly enlarged
      costochondral junctions, and noticeably enlarged long bone metaphyses. In
      addition, one lamb had a dense band of metaphyseal sclerosis beneath the physes
      of all long bones examined. Histopathological findings included small islands and
      columns of chondrocytes and eosinophilic cartilage matrix present in the
      metaphysis. Metaphyseal trabeculae were disorganised and often lined by
      accumulations of pale pink osteoid; similar pale pink osteoid was also present in
      the cortices. Unerupted molar teeth in the affected lambs lacked a layer of
      enamel, and the dentine was irregular with globular basophilia. DIAGNOSIS: The
      gross and histopathological lesions were consistent with a diagnosis of rickets.
      CLINICAL RELEVANCE: Nutritional congenital rickets has not been previously
      diagnosed in sheep, but is a recognised disease of human infants with vitamin D
      deficient mothers. The rickets in affected lambs was most likely associated with
      phosphorus deficiency as a result of the pregnant ewes grazing fodder beet during
      gestation. While vitamin D deficiency was not definitively ruled out in these
      cases, practitioners are alerted to the possible effects of feeding phosphorus
      deficient fodder beet to ewes for long periods during gestation and to 1-year-old
      sheep during important growth periods.

PMID- 27691907
TI  - Investigation of fetal loss in ewe lambs in relation to liveweight changes and
      progesterone concentrations in early to mid gestation.
AB  - AIMS: To investigate associations between changes in liveweight and fetal loss in
      ewe lambs and to determine whether fetal loss was associated with concentrations
      of progesterone in early and mid-gestation. METHODS: Ewe lambs on two commercial
      sheep farms (Flock A; n=504 and Flock B; n=460) in the southern North Island of
      New Zealand were weighed, and body condition score was assessed, prior to
      breeding and throughout pregnancy. Pregnancy diagnosis was undertaken
      approximately 56 (PD1), 80 (PD2) and 110 (PD3) days after the start of breeding
      and fetal loss determined. Blood samples were collected from a cohort of 407 ewe
      lambs between 45-54 and 73-84 days of gestation. Those that subsequently were
      diagnosed with fetal loss (n=16) were matched with ewe lambs that maintained
      pregnancy (n=16), and concentrations of progesterone were measured in the plasma
      samples from these animals. RESULTS: Fetal loss was diagnosed in 55/472 (11.7%)
      pregnant ewes from Flock A and 14/378 (3.7%) from Flock B. In both flocks the
      change in conceptus-free liveweight (CFLW) between PD1 and PD2 differed between
      ewe lambs with and without fetal loss; in Flock A the mean change was -59.9 (95%
      CI=-80.1 to -39.7) g/day vs. -3.43 (95% CI=-9.8 to 3.0) g/day (p<0.001), and in
      Flock B the change was -38.5 (95% CI=-78.9 to 1.94) g/day vs. 79.5 (95% CI=72.6
      86.4) g/day (p<0.001). Similarly in Flock A the mean increase in CFLW between PD2
      and PD3 was lower in ewe lambs with fetal loss than in those that maintained
      pregnancy (25.8 (95% CI=-13.8 to 65.4) g/day vs. 181.9 (95% CI=175.1-188.7)
      g/day) (p<0.001). There was no difference (p>0.05) in early and mid-gestation
      mean concentrations of progesterone in plasma between ewe lambs that had fetal
      loss compared with those that maintained pregnancy. CONCLUSIONS: Ewe lambs with
      fetal loss had a marked reduction in CFLW in the 24-30 days leading up to the
      identification of the fetal loss compared with those that maintained pregnancy.
      Early and mid-gestation concentrations of progesterone in plasma were similar
      between ewe lambs who went on to have fetal loss and those that maintained
      pregnancy.

PMID- 27691908
TI  - A global perspective on education for primary care: a WONCA special edition.

PMID- 27691909
TI  - Corrigendum.

PMID- 27691910
TI  - Primary care education: medical student and young doctors' perspective from
      Brazil, India and Portugal.
AB  - This opinion paper is a collaborative effort describing recent developments in
      primary care education in three different countries; representing diverse
      socioeconomic and political systems. The authors describe their respective
      perspectives from the point of student (Brazil), trainee (Portugal) and young
      doctor (India). The section on Brazil focuses on the response of the medical
      education system to the developments before and after political reforms, leading
      to creation of the Unified Health System. The Indian experience focuses on the
      challenges faced by recently qualified doctors and ongoing debates about the
      medical education system in a highly populated but rapidly growing economy. The
      Portuguese section presents an evolving primary care education system for family
      doctors and describes the detail of the training programme. Education in primary
      care is an ever-evolving process that needs to be adequate for each country's
      health care system. Reading and learning from other experiences may highlight
      education strategies that may be adopted by peers from other countries. Medical
      students, doctors in training and recently qualified doctors are the key
      stakeholders in this process.

PMID- 27691911
TI  - Overcoming the challenges for primary care education - how can WONCA help?

PMID- 27691921
TI  - High production of a class III lantipeptide AmfS in Streptomyces griseus.
AB  - AmfS, a class III lantipeptide serves as a morphogen in Streptomyces griseus.
      Here, we constructed a high production system of AmfS in S. griseus. We isolated
      S. griseus Grd1 strain defective in glucose repression of aerial mycelium
      formation and found it suitable for the overproduction of AmfS. Two expression
      vectors carrying the strong and constitutive ermE2 promoter were constructed
      using a multicopy number plasmid, pIJ702. The use of the Grd1 strain combined
      with the expression vectors enabled high production of AmfS by S. griseus into
      its culture broth. The expression system was also effective for the generation of
      abundant AmfS derived from Streptomyces avermitilis. In addition, site-directed
      mutagenesis revealed the amino acid residues essential for the morphogen activity
      of AmfS. These results indicate that the constructed system enables efficient
      production of class III lantipeptides by Streptomyces.

PMID- 27691922
TI  - Using peer-mediated instruction to support communication involving a student with
      autism during mathematics activities: A case study.
AB  - This study employed an A-B singled subject design to explore the extent to which
      a peer-mediated intervention supported a first-grade student with autism's usage
      both in purpose and frequency of a speech-generating device (SGD) during
      mathematics activities. The intervention involved teaching a peer without a
      disability to encourage the student with autism to use the SGD during partnered
      mathematics activities. Our analysis involved visual and descriptive examination
      of trends and patterns over time, and comparison of means between and within
      phases. We found during the course of this study that (1) the student with
      autism's level of overall communication, which included the relevancy of these
      communicative behaviors, increased; (2) the student with autism's level of
      spontaneous communication acts increased; and (3) the peer became more
      independent with supporting the student with autism's communication. Implications
      for future research and practice are provided.

PMID- 27691923
TI  - Effects of GABA on the expression of type I collagen gene in normal human dermal
      fibroblasts.
AB  - We examined the effects of GABA on type I collagen gene expression in normal
      human dermal fibroblasts. Real-time PCR analysis indicated GABA increased the
      level of type I collagen transcripts, and suppressed the expression of matrix
      metalloproteinase-1, which is a collagen-degrading enzyme. These results suggest
      GABA improves the skin elasticity by regulating type I collagen expression.

PMID- 27691924
TI  - Temperature measurement and control system for transtibial prostheses: Functional
      evaluation.
AB  - The accumulation of heat inside the prosthetic socket increases skin temperature
      and fosters perspiration, which consequently leads to high tissue stress,
      friction blister, discomfort, unpleasant odor, and decreased prosthesis
      suspension and use. In the present study, the prototype of a temperature
      measurement and control (TM&C) system was designed, fabricated, and functionally
      evaluated in a phantom model of the transtibial prosthetic socket. The TM&C
      system was comprised of 12 thermistors divided equally into two groups that
      arranged internal and external to a prosthetic silicone liner. Its control system
      was programmed to select the required heating or cooling function of a thermal
      pump to provide thermal equilibrium based on the amount of temperature difference
      from a defined set temperature, or the amount of difference between the mean
      temperature recorded by inside and outside thermistors. A thin layer of aluminum
      was used for thermal conduction between the thermal pump and different sites
      around the silicone liner. The results showed functionality of the TM&C system
      for thermoregulation inside the prosthetic socket. However, enhancing the
      structure of this TM&C system, increasing its thermal power, and decreasing its
      weight and cost are main priorities before further development.

PMID- 27691934
TI  - Outcomes of cochlear implantation in patients with neurofibromatosis type 2.
AB  - In neurofibromatosis type 2 (NF2) bilateral vestibular schwannomas (VS) or their
      treatment usually results in bilateral hearing loss. Cochlear implantation (CI)
      was traditionally not used in these patients due to concern that retrocochlear
      disease would render the implant ineffective. This paper describes the auditory
      outcomes of CI in 13 patients with NF2 and includes patients with untreated VS
      and patients undergoing VS removal with cochlear nerve preservation. The non-user
      rate was 7.7%. Of the active users, median CUNY score was 98%, median BKB score
      in quiet was 90% and median BKB score in noise was 68%. CI is a viable option in
      selected patients with NF2.

PMID- 27691935
TI  - COMBINATION THERAPY WITH FLUOXETINE AND ALPRAZOLAM TO CONTROL ANXIETY IN A HAND
      REARED SNOW LEOPARD (UNCIA UNCIA).
AB  - A captive hand-reared adult male snow leopard ( Uncia uncia ) was treated for
      anxiety associated with taunting from visitors, the presence of large crowds, and
      introduction to a female for breeding. Behaviors included shaking, chewing on
      tail, panting, panicking, and bouncing off the viewing glass, pacing, and
      avoidance of the female. Combination therapy of oral fluoxetine and alprazolam
      were administered initially to minimize anxious behaviors while the fluoxetine
      achieved therapeutic levels. The alprazolam was tapered completely and was only
      used episodically on two occasions. Although a palatability issue with alprazolam
      initially prevented consistent dosing, anxious behavior was eliminated and
      successful breeding behavior was achieved for the first time. After 44 mo of
      therapy, there have been no anxious behaviors requiring additional medications,
      two additional breeding behaviors observed, and no evidence of adverse side
      effects with long-term use.

PMID- 27691936
TI  - EVALUATION OF ETORPHINE AND MIDAZOLAM ANESTHESIA, AND THE EFFECT OF INTRAVENOUS
      BUTORPHANOL ON CARDIOPULMONARY PARAMETERS IN GAME-RANCHED WHITE RHINOCEROSES
      (CERATOTHERIUM SIMUM).
AB  - Nineteen white rhinoceroses ( Ceratotherium simum ) were anesthetized with 4 mg
      of etorphine hydrochloride; 35-40 mg of midazolam; and 7,500 international units
      of hyaluronidase for dehorning purposes at a game ranch in South Africa, to
      investigate this anesthetic combination. Median time to recumbency was 548 sec
      (range 361-787 sec). Good muscle relaxation and no muscle rigidity or tremors
      were observed in 18 animals, and only 1 individual showed slight tremors. In
      addition, all animals received butorphanol i.v. 5 min after recumbency at the
      ratio of 10 mg of butorphanol per 1 mg of etorphine. Blood gas and selected
      physiologic parameters were measured in the recumbent animal, immediately before
      and 10 min after the administration of butorphanol. Statistically significant
      improvements were observed in blood gas physiologic and cardiopulmonary
      parameters 10 min after the administration of butorphanol, with a reduction in
      arterial partial pressure of carbon dioxide, systolic blood pressure, and heart
      rate and an increase in pH, arterial partial pressure of oxygen, oxygen
      saturation, and respiratory rate (all P < 0.005). After i.v. naltrexone reversal,
      recovery was uneventful, and median time to walking or running was 110 sec (range
      71-247 sec). The results indicate etorphine and midazolam combination is an
      effective alternative anesthetic protocol and produces good muscle relaxation.
      Furthermore, i.v. butorphanol was associated with improved blood gas values and
      cardiopulmonary function for at least 10 min postinjection.

PMID- 27691937
TI  - MEASUREMENT OF INTRAOCULAR PRESSURE IN THE DOMESTIC PIGEON (COLUMBIA LIVIA).
AB  - The purpose of this study was to establish intraocular pressure values in
      clinically normal pigeons. One hundred (52 male and 48 female) healthy pigeons (
      Columbia livia ) of six different breeds, ranging in age from 20 to 51 mo were
      used in the study. Pigeons were gently physically restrained in a dorsoventral
      position without any pressure or extension to the head and neck. A rebound
      tonometer with a disposable probe was held horizontally and 4-5 mm from the
      central corneal surface. Calibration of the device was set to "P." Overall, the
      mean +/- SD intraocular pressure values of all eyes were 6.1 +/- 0.9 mmHg
      (ranging from 3 to 9 mmHg). Mean +/- SD values for left and right eyes were 6.1
      +/- 1.0 and 6.0 +/- 1.2 mmHg, respectively. There was no statistically
      significant difference in IOP between the left eye and right eye or between males
      and females (P = 0.49; P = 0.74). Analysis of variance revealed that there were
      no significant differences in the IOP between the breeds (P = 0.22).

PMID- 27691938
TI  - MEDICAL MANAGEMENT OF COELOMIC DISTENTION, ABNORMAL SWIMMING, SUBSTRATE
      RETENTION, AND HEMATOLOGIC CHANGES IN A REEF MANTA RAY (MANTA ALFREDI).
AB  - An adult, female, reef manta ray (Manta alfredi) was evaluated for abnormal
      swimming and coelomic distention after colliding with a floating dock in an
      exhibit. Initial clinical signs included abnormal posture and swimming. Clinical
      signs progressed to include muscle wasting, poor body condition, and coelomic
      distention. Further diagnostics revealed excessive exhibit substrate within the
      gastrointestinal tract, gastric ulcers, free coelomic fluid, possible spinal
      lesion, possible uterine abnormality, and hematologic changes. The ray was
      treated with repeated gastroscopic examinations to remove substrate from the
      stomach. Psyllium and mineral oil were administered in gel food to assist with
      passage of substrate through the gastrointestinal tract. Gastric ulcers were
      treated with sucralfate. Vitamin B complex, iron dextran, and Yunnan Paiyao were
      used to treat the anemia. Amikacin and sulfadimethoxine-ormetoprim were
      administered for suspected bacterial and coccidial infections, respectively. Over
      the course of 11 mo the ray returned to normal health.

PMID- 27691939
TI  - CLINICAL CHALLENGE: RENAL ADENOCARINCOMA IN A BEADED LIZARD (HELODERMA HORRIDUM
      HORRIDUM).

PMID- 27691940
TI  - POISONING BY THE SWAINSONINE-CONTAINING PLANT SIDA CARPINIFOLIA IN CAPTIVE SAMBAR
      DEER (CERVUS UNICOLOR).
AB  - Plant intoxications in wildlife are difficult to diagnose, are overlooked, or are
      sometimes even neglected. Hence, factors that induce wild animals to ingest
      poisonous plants have not been sufficiently documented. An outbreak of
      glycoprotein storage disease in sambar deer ( Cervus unicolor ), induced by
      ingestion of the swainsonine-containing plant, common wireweed (Sida
      carpinifolia), is reported. Nine out of 55 deer held by a zoo in Brazil were
      affected. The poisoning was characterized by emaciation and neurologic signs
      followed by unexpected death in some of the animals. Animals presented abnormal
      consciousness, posterior paresis, and musculoskeletal weakness; less evident were
      vestibulo-cerebellar signs. Histologically, there was vacuolation of neurons and
      epithelial cells of the pancreatic acines, thyroid follicules, and renal tubules.
      Furthermore, in the central nervous system were axonal degeneration, necrosis,
      and loss of neurons. Three factors may lead to the ingestion of S. carpinifolia
      by sambar deer: 1) A grazing field with only S. carpinifolia as a source of
      forage; 2) a large number of animals kept in this field; and 3) a hierarchy
      within a cervid group in which dominant males isolated and displaced juvenile and
      weaker adult males, leaving them with access to only S. carpinifolia.

PMID- 27691941
TI  - INFECTIOUS DISEASE AND TOXICOLOGICAL MONITORING OF STRANDED PACIFIC HARBOR SEALS
      (PHOCA VITULINA RICHARDSI) IN COOK INLET AS SURROGATES FOR MONITORING ENDANGERED
      BELUGAS (DELPHINAPTERUS LEUCAS).
AB  - Pacific harbor seals ( Phoca vitulina richardsi) and belugas ( Delphinapterus
      leucas ) eat many of the same prey species, occupy the same geographic area, and
      demonstrate site fidelity in Cook Inlet, Alaska. Although most direct research
      involving the critically endangered belugas is currently prohibited, studying
      harbor seals may provide important information about this beluga population. In
      recent years, harbor seal populations in Alaska have declined for unknown
      reasons. As part of its stranding program, the Alaska SeaLife Center (ASLC)
      managed 59 cases of live and dead stranded harbor seals from Cook Inlet between
      1997 and 2011. Animals were screened for a variety of diseases and contaminants
      of concern. Animals were negative by serology to the following diseases: avian
      influenza, canine distemper virus, dolphin morbillivirus, porpoise morbillivirus,
      Leptospira canicola, L. grippotyphosa, L. pomona, Neospora caninum , Sarcocystis
      neurona , and Toxoplasma gondii . Positive titers were found against Brucella
      spp., phocine distemper virus, seal herpesvirus-1, L. bratislava, L. hardjo, and
      L. icterohemorrhagiae. All titers were stable or declining except in one animal
      with an increasing titer for seal herpesvirus-1. Fecal pathogen screenings
      identified normal flora as well as stable or declining low levels of potentially
      pathogenic and opportunistic bacteria, though most were of little concern for
      seal health. In most animals, toxicology screening showed that the majority of
      tested contaminants were below detectable limits. The level of evidence of
      exposure to pathogens of concern was low in harbor seals. Although the infectious
      disease burden and contaminant levels in belugas in Cook Inlet cannot be
      definitively determined without direct testing, pathogen and contaminant exposure
      is expected to be similar to that found in harbor seals in this region, as the
      harbor seals and belugas share the habitat and food resources.

PMID- 27691944
TI  - AAZV PUBLICATIONS AVAILABLE.

PMID- 27691942
TI  - LEISHMANIA SPP. IN DIDELPHIS SPP. FROM NORTHEASTERN BRAZIL.
AB  - The synanthropic behavior of marsupials of the genus Didelphis in endemic areas
      of leishmaniasis suggests that these animals may play an important role in the
      epidemiology of this infection. The aim of the present study was to detect
      Leishmania spp. DNA in Didelphis albiventris (white-eared opossum) and Didelphis
      aurita (big-eared opossum) living in forested and peridomestic areas of
      northeastern Brazil. Blood samples were collected from 25 animals (23 D.
      albiventris and 2 D. aurita ) by cardiac puncture and then analyzed via PCR.
      Leishmania (Viannia) braziliensis DNA complex was detected in 4 (16%) of the 25
      samples, whereas no samples scored positive for Leishmania (Leishmania) donovani
      complex. Our data suggest that D. albiventris participates in the wild enzootic
      cycle of the L. (V.) braziliensis complex. Therefore, humans living in this area
      are at risk of infection, because Didelphis species are in constant movement
      between wild and urban environments.

PMID- 27691945
TI  - PREVALENCE OF HEALED LONG-BONE FRACTURES IN WILD CARNIVORES FROM THE NORTHEASTERN
      UNITED STATES.
AB  - Museum specimens representing 12 species of terrestrial carnivores from the
      northeastern United States were inspected for evidence of healed long-bone
      fractures. Of 413 individuals, 18 (4.4%) exhibited healed fractures. Thirteen
      (72.2%) occurred in hind limbs; five (27.8%) occurred in forelimbs. Mustelids had
      the highest prevalence of healed long-bone fractures (38.8%) of all observed
      fractures. Within family, 5.6% of Canidae and 2.8% of Mustelidae exhibited healed
      fractures. Bobcats had the highest taxon prevalence of fractures, 18%.
      Observational data to assess use of and behavior near roads could provide insight
      to causes of fracture. Capture in combination with noninvasive examination
      techniques could be employed to determine incidence of healed fractures in wild
      populations. Individuals with healed fractures could then be tracked via radio
      telemetry to determine if these animals behave differently than uninjured
      conspecifics, and assess long-term survivability and fitness.

PMID- 27691946
TI  - PLASMA BIOCHEMISTRY AND HEMATOLOGY REFERENCE VALUES OF CAPTIVE PANTHER CHAMELEONS
      (FURCIFER PARDALIS) WITH SPECIAL EMPHASIS ON SEASONALITY AND GENDER DIFFERENCES.
AB  - Blood samples of 86 captive panther chameleons (Furcifer pardalis) were collected
      in January and August from the ventral coccygeal vein in order to establish
      reference intervals of clinical healthy individuals under similar husbandry
      conditions for plasma biochemistry and hematology for this species. Significant
      differences were found in phosphorus, glucose, total protein, albumin, and white
      blood cell count between males and females in both seasons. Calcium, alanine
      aminotransferase, aspartate aminotransferase, and lactate dehydrogenase varied in
      only one season between genders. Significant differences between summer and
      winter values were present in both genders for uric acid, calcium, phosphorus,
      glucose, total protein, creatine kinase, and albumin. Additionally, females
      showed seasonal variations for alanine aminotransferase and aspartate
      aminotransferase whereas packed cell volume varied in males. Gravid females had
      significantly higher body weights and increased values for uric acid, calcium,
      phosphorus, alanine aminotransferase, total protein, and albumin. Cytomorphologic
      characteristics of blood cells in stained blood films were evaluated to serve as
      additional parameters for hematology.

PMID- 27691947
TI  - PHARMACOKINETIC EVALUATION OF MELOXICAM AFTER INTRAVENOUS AND INTRAMUSCULAR
      ADMINISTRATION IN NILE TILAPIA (OREOCHROMIS NILOTICUS).
AB  - Critically evaluating the pharmacokinetic behavior of a drug in the body provides
      crucial information about how to effectively treat a patient. Pharmacokinetic
      studies that exist in fish have primarily focused on drugs used to treat
      infectious disease, with minimal attention given to analgesic drugs. The
      objective of this study was to determine the pharmacokinetics of meloxicam (1
      mg/kg) in Nile tilapia ( Oreochromis niloticus ) (n = 12). A single dose of
      meloxicam was administered either i.v. or i.m. Blood samples were obtained at
      predetermined times after drug injection. Plasma meloxicam concentrations were
      determined by a validated liquid chromatography/mass spectrometry method, and
      noncompartmental pharmacokinetic analysis was performed. The mean peak plasma
      concentration after i.m. injection was 1.95 MUg/ml. The mean terminal half-life
      of meloxicam after i.v. and i.m. administration was 1.36 and 1.8 hr,
      respectively. The area under the plasma concentration-versus-time curve
      extrapolated to infinity was 11.26 hr.MUg/ml after i.v. administration and 5.72
      hr.MUg/ml after i.m. administration. Bioavailability of meloxicam after i.m.
      administration was approximately half that of i.v. administration. Elimination
      was rapid in both the i.m. and i.v. routes of administration, suggesting that
      maintaining clinically relevant plasma concentrations may be difficult using this
      dose. This study represents the first pharmacokinetic evaluation of a
      nonsteroidal anti-inflammatory drug in a fish species, and further studies
      evaluating efficacy are needed.

PMID- 27691948
TI  - RADIOGRAPHIC THORACIC ANATOMY OF THE RED PANDA (AILURUS FULGENS).
AB  - The red panda ( Ailurus fulgens ) is classified as an endangered species by the
      International Union for Conservation of Nature and Natural Resources. The natural
      distribution of the red panda is in the Himalayas and southern China. Thoracic
      diseases such as dirofilariasis, hypertrophic cardiomyopathy, tracheal
      obstruction, lung worm infestation, and pneumonia have been reported in the red
      panda. The aim of this study was to describe the normal radiographic thoracic
      anatomy of captive red pandas as a species-specific reference for routine health
      examinations and clinical cases. Right lateral (RL) and dorsoventral (DV)
      inspiratory phase views of the thorax were obtained in 11 adult captive red
      pandas. Measurements were made and ratios calculated to establish reference
      ranges for the mean vertebral heart score on the RL (8.34 +/- 0.25) and DV (8.78
      +/- 0.34) views and the mean ratios of the caudal vena cava diameter to the
      vertebral body length above tracheal bifurcation (0.67 +/- 0.05) and tracheal
      diameter to the width of the third rib (2.75 +/- 0.24). The majority of animals
      (10/11) had 14 thoracic vertebrae, except for one animal that had 15 thoracic
      vertebrae. Rudimentary clavicles were seen in 3/11 animals. The ovoid, oblique
      cardiac silhouette was more horizontally positioned and elongated in older
      animals. A redundant aortic arch was seen in the oldest animal. The trachea was
      seen with mineralized cartilage rings in all animals. The carina was clearly seen
      in the majority of animals (10/11). Variations exist in the normal radiographic
      thoracic anatomy of different species. Knowledge of the normal radiographic
      thoracic anatomy of the red panda should prove useful for routine health
      examinations and in the diagnosis of thoracic diseases.

PMID- 27691949
TI  - HEMATOLOGY AND PLASMA BIOCHEMISTRY INTERVALS FOR CAPTIVE-BORN CALIFORNIA TIGER
      SALAMANDERS (AMBYSTOMA CALIFORNIENSE).
AB  - Hematology and plasma biochemistry parameters were determined for 34 captive-born
      California tiger salamanders ( Ambystoma californiense ). The animals were
      manually restrained for general examination and venipuncture. This is the first
      comprehensive report of hematology and plasma biochemistry parameters in
      apparently healthy California tiger salamanders and may serve as a reference for
      clinical assessment and future study of this species.

PMID- 27691951
TI  - BILATERAL HYDRONEPHROSIS IN A SUGAR GLIDER (PETAURUS BREVICEPS).
AB  - An adult, intact male sugar glider ( Petaurus breviceps ) presented for acute
      caudal abdominal swelling. Treatment by the referring veterinarian included
      aspiration of urine from the swelling. On physical examination, mild depression,
      pale mucus membranes, and caudal abdominal swelling were noted. Focused
      ultrasonographic assessment revealed a fluid-filled caudal abdominal structure
      and subjective bladder wall thickening. The following day, the sugar glider was
      severely depressed. Hematology results included hypoglycemia, hyperkalemia,
      hyponatremia, and azotemia. Ultrasonography revealed bilateral hydronephrosis and
      hydroureter. Despite supportive care, the animal died. Postmortem examination
      confirmed bilateral ureteral dilation, renal petechial hemorrhage, and dilation
      of the right renal pelvis. Submucosal edema, hemorrhage, and lymphoplasmacytic
      infiltration of the urinary bladder, ureters, and renal pelvises were noted.
      Hyperplasia of the urinary bladder and ureteral epithelium, coupled with
      inflammation, may have caused functional obstruction leading to bilateral
      hydronephrosis and hydroureter. This is the first reported case of hydronephrosis
      in a marsupial.

PMID- 27691950
TI  - CARDIOVASCULAR EFFECTS OF ETORPHINE, AZAPERONE, AND BUTORPHANOL COMBINATIONS IN
      CHEMICALLY IMMOBILIZED CAPTIVE WHITE RHINOCEROS (CERATOTHERIUM SIMUM).
AB  - Chemical capture is an essential tool in the management and conservation of white
      rhinoceros ( Ceratotherium simum ); however, cardiovascular responses in
      immobilized megaherbivores are poorly understood. Blood pressure and heart rate
      responses in rhinoceros immobilized with etorphine or etorphine plus azaperone,
      and the effects of subsequent i.v. butorphanol administration were investigated.
      Six white rhinoceros were used in a randomized crossover study design with four
      interventions: 1) etorphine i.m.; 2) etorphine plus azaperone i.m.; 3) etorphine
      i.m. and butorphanol i.v.; and 4) etorphine plus azaperone i.m., and butorphanol
      i.v. Etorphine resulted in hypertension and tachycardia in immobilized rhinoceros
      on initial measurements. Over the 25-min study period, blood pressures and heart
      rate declined. Heart rates were slower, although the rhinoceros were still
      tachycardic, and blood pressures lower during the whole study period in animals
      immobilized with etorphine and azaperone compared with those that received only
      etorphine. Butorphanol administration resulted in lower arterial blood pressures
      and heart rates in etorphine-immobilized rhinoceros. In rhinoceros immobilized
      with etorphine and azaperone, heart rate slowed following administration of
      butorphanol i.v., although blood pressures remained unchanged. Azaperone reduced
      hypertension associated with etorphine immobilization, but animals remained
      tachycardic. Administration of butorphanol to etorphine/azaperone-immoblized
      rhinoceros lowered heart rate to values approaching normal resting levels without
      altering blood pressure.

PMID- 27691952
TI  - GROSS ANATOMY AND SURGICAL APPROACH TO THE HUMERAL SHAFT IN GIANT ANTEATER
      (MYRMECOPHAGA TRIDACTYLA).
AB  - Anteater forelimbs are distinguished morphologically from domestic animals,
      especially due to their unique movement and their natural habits. A knowledge of
      the pectoral limb anatomy and the proper surgical approach are fundamental to
      success in osteosynthesis and other surgeries. This study aimed to describe the
      muscles and neurovascular structures of the pectoral limb and the surgical
      approach to the humeral shaft of the giant anteater ( Myrmecophaga tridactyla ).
      Dissections of the forelimbs of seven cadavers were performed to identify the
      major muscles and neurovascular structures. Three of these animals' contralateral
      forearms were used to simulate the surgical approach to the humeral shaft. Some
      specific characteristics of the muscle morphology were biceps muscle had two
      heads, triceps muscle had three heads, and there was an olecranon-epicondylar
      muscle. To expose the shaft of the humerus, it was necessary to incise the
      superficial pectoral muscle and separate the heads of the biceps muscle. Due to
      the anatomical characteristics of the humerus, the craniomedial approach was the
      most appropriate because it accommodated the anatomical peculiarities of the
      giant anteater.

PMID- 27691953
TI  - PROSPECTIVE POPULATION MANAGEMENT FOR HEPATITIS B IN THE CHIMPANZEE (PAN
      TROGLODYTES) SSP(r) POPULATION.
AB  - Hepatitis B virus causes horizontally transmitted infectious hepatopathy of
      primates and may progress to hepatocellular carcinoma. Historically, a small
      number of chimpanzees ( Pan troglodytes ) living in accredited North American
      zoos have been confirmed with positive hepatitis B serology consistent with
      exposure. However, the overall status for this population and the interpretation
      of these individual test results have not been established previously. The
      current U.S. zoo-housed population (n = 259) was assessed serologically for
      hepatitis B by surface protein antigen (HbsAg) and surface antibodies (anti-Hbs).
      Signalment, origin, current health status, history of liver disease, and
      hepatitis B vaccination history were obtained for each animal. Serologic status
      was measured directly in 86.5% (n = 224) of these individuals, with 2.2% (n = 5)
      of the study population determined to be chronically infected by positive HbsAg
      and negative anti-Hbs status. Additionally, 11.6% (n = 26) of the directly
      measured population tested were HbsAg negative and anti-Hbs positive, which was
      indicative of viral exposure. No animals were determined to be acutely infected
      as HbsAg and anti-Hbs positive. Although these results demonstrated a relatively
      low prevalence of hepatitis B infection among these chimpanzees, the varied
      serologic results between institutions underscored the importance of routine
      serologic testing, especially at times of proposed transfers, and consideration
      of species vaccination protocols.

PMID- 27691954
TI  - DETECTION OF COXIELLA BURNETII INFECTION IN A SAHARAWI DORCAS GAZELLE (GAZELLA
      DORCAS NEGLECTA).
AB  - Coxiella burnetii, the causative agent of Q fever, can infect a wide range of
      host species, but limited information exists on the occurrence and implications
      of infection in wild species. This study describes a natural infection in a
      population of dorcas gazelles ( Gazella dorcas ) from a zoo. A 9-yr-old male
      Saharawi dorcas gazelle ( Gazella dorcas neglecta) tested positive on enzyme
      linked immunosorbent assay (ELISA) and fecal polymerase chain reaction (PCR).
      Despite treatment with oxytetracycline, the animal did not clear the infection
      after 6 mo, as confirmed by a PCR test on a semen sample. This is the first
      report of a Saharawi dorcas gazelle infection with C. burnetii and the first time
      that C. burnetii was detected in semen from a zoo animal, suggesting the
      possibility of venereal transmission in captive wild species. This may have major
      implications for management of zoo populations, particularly in endangered
      species.

PMID- 27691955
TI  - DIVERSITY OF THE TYPE 1 INTRON-ITS REGION OF THE 18S rRNA GENE IN
      PSEUDOGYMNOASCUS SPECIES FROM THE RED HILLS OF KANSAS.
AB  - Gypsum caves found throughout the Red Hills of Kansas have the state's most
      diverse and largest population of cave-roosting bats. White-nose syndrome (WNS),
      a disease caused by the fungus Pseudogymnoascus destructans, which threatens all
      temperate bat species, has not been previously detected in the gypsum caves as
      this disease moves westward from the eastern United States. Cave soil was
      obtained from the gypsum caves, and using the polymerase chain reaction, a 624
      nucleotide DNA fragment specific to the Type 1 intron-internal transcribed spacer
      region of the 18S rRNA gene from Pseudogymnoascus species was amplified.
      Subsequent cloning and DNA sequencing indicated P. destructans DNA was present,
      along with 26 uncharacterized Pseudogymnoascus DNA variants. However, no evidence
      of WNS was observed in bat populations residing in these caves.

PMID- 27691956
TI  - MOLECULAR IDENTIFICATION AND SEQUENCE CHARACTERIZATION OF MYCOPLASMAS IN FREE
      LIVING BIRDS OF PREY.
AB  - Mycoplasma spp. have been detected in birds of prey, but their prevalence in free
      living raptors and their significance to birds' health need further
      investigation. Molecular techniques have been increasingly used to identify
      mycoplasmas in various avian species, due to the fastidious nature of these
      pathogens hampering traditional bacteriologic tests. This study reports the
      identification of 23 novel mycoplasma sequences during the monitoring of 62 birds
      of prey on admission to wildlife centers in Sardinia, Italy. Molecular
      investigation performed on pharyngeal swabs revealed 26 birds positive to
      Mycoplasma (42%). Sequence analysis based on 16S rRNA, 16S-23S rRNA intergenic
      spacer, and RNA polymerase beta subunit (rpoB) gene highlighted cluster
      assignment and phylogenetic relationships among the identified types, classified
      within the hominis group. Additionally, Ornithobacterium rhinotracheale ,
      associated with respiratory disease in poultry, was identified in 17 birds (27%).
      Potential coinfection and mycoplasma opportunistic nature present implications
      for raptor species conservation.

PMID- 27691957
TI  - ISOLATION AND IDENTIFICATION OF MICROSPORUM CANIS FROM ASIAN ELEPHANTS (ELEPHAS
      MAXIMUS) IN THE CHONGQING ZOO, CHINA.
AB  - Skin diseases affect millions of people and animals worldwide, including Asian
      elephants. This study sought to determine the pathogen of skin diseases that
      occurred in Asian elephants in Chongqing Zoo, China. The isolated fungus was
      identified through its cultural characteristics, morphology, and polymerase chain
      reaction (PCR) amplification. The PCR amplification using common fungal primers
      (ITS1 and ITS4) determined that the pathogen was 99.7% homologous to Microsporum
      canis. This is the first report on elephants infected with Microsporum canis in
      China.

PMID- 27691958
TI  - RETROSPECTIVE ANALYSIS OF ADULT-ONSET CARDIAC DISEASE IN FRANCOIS' LANGURS
      (TRACHYPITHECUS FRANCOISI) HOUSED IN U.S. ZOOS.
AB  - Cardiac disease is a common condition in captive primates, and multiple cases in
      Francois' langurs ( Trachypithecus francoisi ) were noted on review of the
      Species Survival Plan studbook. To determine the prevalence of cardiac disease in
      this species, surveys were distributed to current and previous holding
      institutions (n = 23) for the U.S. studbook population (n = 216). After exclusion
      of stillbirths (n = 48), animals less than 1 yr of age (n = 8), and animals
      housed internationally (n = 2), a study group (n = 158) was identified for this
      analysis. Robust data was received for 98.7% (n = 156) of the study group and
      antemortem and postmortem cardiac abnormalities were reported for 25.3% (n = 40)
      of these animals. Eight animals were reported as medically managed for clinical
      cardiac disease, and three of these were alive at the time of survey. Six of 11
      animals with radiographic cardiac silhouette enlargement antemortem were noted
      with cardiomegaly on postmortem examination. Of 102 deceased animals in the study
      group, four were identified with dilated cardiomyopathy, and varying degrees of
      myocardial fibrosis was observed in 18 animals. Langurs with cardiac fibrosis
      were found to be significantly older than langurs without cardiac fibrosis (P =
      0.003) and more commonly were male (P = 0.036). Screening tests for cardiac
      disease, such as thoracic radiographs and echocardiography, are recommended to
      diagnose affected animals earlier, to monitor progression of disease, and to
      guide treatment, although they should be interpreted with caution because of
      apparent insensitivity when compared with pathologic results.

PMID- 27691959
TI  - TREATMENT OF DIABETES MELLITUS IN A GOLDEN LION TAMARIN (LEONTOPITHECUS ROSALIA)
      WITH THE GLUCAGON-LIKE PEPTIDE-1 MIMETIC EXENATIDE.
AB  - An 8-yr-old male golden lion tamarin ( Leontopithecus rosalia ) was diagnosed
      with diabetes mellitus based on hyperglycemia and persistent glycosuria. Initial
      treatment consisted of the oral antihyperglycemic medications glipizide and
      metformin that resulted in decreased blood glucose concentrations; however,
      marked glycosuria persisted. Insufficient improvement on oral antihyperglycemic
      therapy and poor feasibility of daily subcutaneous insulin therapy led to an
      investigation into an alternative therapy with extended-release exenatide, a
      glucagon-like peptide-1 (GLP-1) mimetic, at a dosage of 0.13 mg/kg subcutaneously
      once per month. Following treatment with exenatide, the persistent glycosuria
      resolved, the animal maintained normal blood glucose concentrations, and had
      lower serum fructosamine concentrations compared to pretreatment levels. Based on
      these findings, extended-release exenatide could be considered as a therapeutic
      option in nonhuman primates with diabetes mellitus that do not respond to oral
      antihyperglycemics and in which daily subcutaneous insulin is not feasible.

PMID- 27691960
TI  - EVALUATION OF SERUM FERRITIN AND SERUM IRON IN FREE-RANGING BLACK RHINOCEROS
      (DICEROS BICORNIS) AS A TOOL TO UNDERSTAND FACTORS AFFECTING IRON-OVERLOAD
      DISORDER.
AB  - Iron overload disorder (IOD) is a significant health issue for captive black
      rhinoceros ( Diceros bicornis ). Measurement of serum ferritin with a validated
      rhinoceros ferritin ELISA has been used extensively to detect animals in U.S.
      zoos that are at risk of developing IOD. However, there is limited information on
      serum ferritin levels in free-ranging black rhinoceros using this same assay.
      Serum ferritin, iron, and gamma-glutamyl transpeptidase (GGT) were determined in
      194 black rhinoceros from southern Africa. Mean ferritin in free-ranging black
      rhinoceros (290.54 +/-247.4 ng/ml) was significantly higher than in free-ranging
      white rhinoceros (64.0 +/- 102.4 ng/ml) sampled in this study from Kruger
      National Park, South Africa. However, there were no significant differences
      between genders or age groups. Ferritin values varied with geographical location
      of the black rhinoceros, although this was not clinically significant. Serum iron
      values were also higher in black rhinoceros (40.4 +/- 19.1 MUmol/L) compared to
      white rhinoceros (29.7 +/- 10.7 MUmol/L). There was no association between
      ferritin and GGT. This study provides serum ferritin, iron, and GGT values from
      free-ranging black rhinoceros that can be used for as comparative target values
      for captive animals.

PMID- 27691961
TI  - CONGENITAL CLEFT PALATE AND CARDIAC SEPTAL DEFECTS IN A NEONATAL SOUTHERN BLACK
      RHINOCEROS (DICEROS BICORNIS MINOR).
AB  - A female Southern black rhinoceros ( Diceros bicornis minor) calf died
      unexpectedly at less than 12 hr of age, after an uncomplicated birth and
      uneventful early postpartum period. Gross necropsy revealed a 15-cm full
      thickness cleft palate, a patent foramen ovale, and four septal defects ranging
      from 0.3 to 1 cm in diameter. Histologic findings did not reveal any significant
      abnormalities. Karyotyping did not indicate any significant numerical or
      structural chromosomal abnormalities.

PMID- 27691962
TI  - CUTANEOUS SQUAMOUS CELL CARCINOMA IN A PANTHER CHAMELEON (FURCIFER PARDALIS) AND
      TREATMENT WITH CARBOPLATIN IMPLANTABLE BEADS.
AB  - A 3-yr-old male panther chameleon (Furcifer pardalis) presented with bilateral
      raised crusted skin lesions along the lateral body wall that were found to be
      carcinoma in situ and squamous cell carcinoma. Similar lesions later developed on
      the caudal body wall and tail. A subcutaneous implantable carboplatin bead was
      placed in the first squamous cell carcinoma lesion identified. Additional new
      lesions sampled were also found to be squamous cell carcinomas, and viral
      polymerase chain reaction was negative for papillomaviruses and herpesviruses.
      Significant skin loss would have resulted from excision of all the lesions, so
      treatment with only carboplatin beads was used. No adverse effects were observed.
      Lesions not excised that were treated with beads decreased in size. This is the
      first description of cutaneous squamous cell carcinoma and treatment with
      carboplatin implantable beads in a panther chameleon.

PMID- 27691963
TI  - EVALUATION OF POTENTIAL RISK FACTORS ASSOCIATED WITH CATARACT IN CAPTIVE MACARONI
      (EUDYPTES CHRYSOLOPHUS) AND ROCKHOPPER PENGUINS (EUDYPTES CHRYSOCOME).
AB  - Complete ophthalmic examinations were performed on 160 Macaroni penguins (
      Eudyptes chrysolophus ) and 90 Rockhopper penguins ( Eudyptes chrysocome ) at
      eight North American zoological institutions. Cataract prevalence in the Macaroni
      population was 46.5% (n = 74) of penguins and 42.3% (135/319) of eyes. Cataract
      prevalence in the Rockhopper population was 45.5% (n = 40) of penguins and 40.6%
      (73/180) of eyes. The mean age of Macaroni penguins without ocular disease was
      7.4 +/- 5.8 yr, while that of Rockhoppers was 9.8 +/- 6.4 yr. Risk factors for
      cataract were examined through husbandry surveys completed by each institution
      and by evaluation of light intensity and ultraviolet (UV) light measurements
      acquired in each penguin exhibit. Risk factors associated with cataract in
      Macaroni penguins included age, dietary smelt, hand-feeding, and fluorescent
      exhibit lighting. Risk factors associated with cataract in Rockhopper penguins
      included age, dietary capelin, increasing population density, and increasing
      length of minimum photoperiod. Factors associated with decreased odds of cataract
      in Macaroni penguins included saltwater pool, monitoring of water quality for
      salinity, pH, and alkalinity; use of water additives; presence of pool filtration
      and sterilization systems; use of metal halide lightbulbs; increasing light
      intensity; and UV spectrum lighting. Factors associated with decreased odds of
      cataract in Rockhoppers included dietary herring and krill, increasing exhibit
      land area, pool temperature monitoring, increasing maximum photoperiod, and
      increasing minimum UV light.

PMID- 27691964
TI  - CLINICAL CHALLENGE.

PMID- 27691965
TI  - ANESTHESIA IN A CAPTIVE JUVENILE BLACK RHINOCEROS (DICEROS BICORNIS) FOR MAGNETIC
      RESONANCE IMAGING AND COMPUTED TOMOGRAPHY.
AB  - A hand-reared, 53-kg, female, 30-day-old black rhinoceros ( Diceros bicornis )
      calf presented for magnetic resonance imaging and computed tomography after
      demonstrating neurologic signs. The rhino was premedicated intramuscularly with
      butorphanol and midazolam, yielding satisfactory sedation. Induction was achieved
      using intravenous propofol until the trachea could be intubated. Anesthesia was
      maintained with sevoflurane in 100% oxygen (mean end-tidal concentration of 2 +/-
      0.5%). Mean values recorded during anesthesia included were heart rate, end-tidal
      carbon dioxide, respiratory rate, noninvasive blood pressure, and pulse oximetry.
      A balanced electrolyte solution of 10 mL/kg per hour was given intravenously. It
      was concluded that anesthesia was safely induced and maintained with a
      combination of butorphanol, midazolam, propofol, and sevoflurane. Total
      anesthesia time was 3 hr, with no perianesthetic complications and an uneventful
      recovery.

PMID- 27691966
TI  - INVESTIGATION ON CRYPTOSPORIDIUM INFECTIONS IN WILD ANIMALS IN A ZOO IN ANHUI
      PROVINCE.
AB  - To assess Cryptosporidium infections among wild animals in a zoo located in Anhui
      province, we conducted an investigation on the fecal samples collected from 44
      primates, 41 herbivores, 44 carnivores and omnivores, and 103 birds in the zoo
      with the use of Sheather's sugar flotation technique and modified acid-fast
      staining. Cryptosporidium oocysts were detected in the fecal samples from six
      primates, two herbivores, four carnivores and omnivores, and seven birds by using
      Sheather's sugar flotation technique; the prevalence of Cryptosporidium infection
      in primates, herbivores, carnivores and omnivores and birds was 13.64, 4.88,
      9.09, and 6.80%, respectively. Modified acid-fast staining detected the presence
      of Cryptosporidium oocysts in the fecal samples of one primate, three herbivores,
      0 carnivores and omnivores, and one bird, and the prevalence of Cryptosporidium
      infection in primates, herbivores, carnivores and omnivores and birds was 2.27,
      7.32, 0.00, and 0.97%, respectively. Polymerase chain reaction-restriction
      fragment-length polymorphism (PCR-RFLP) and phylogenetic analysis with the use of
      the neighbor-joining (NJ) method based on the aligned partial small-subunit (SSU)
      rRNA gene sequences showed that the protozoan pathogen isolated from primates was
      Cryptosporidium hominis and the pathogen isolated from camels ( Camelus
      dromedarius ) was Cryptosporidium andersoni. Subtyping the Cryptosporidium
      hominis by 60-kDa glycoprotein (GP60) gene phylogenetic analysis showed the
      Cryptosporidium hominis belongs to the subtype IdA and IbA.

PMID- 27691967
TI  - ISONIAZID AND RIFAMPIN PHARMACOKINETICS IN TWO ASIAN ELEPHANTS (ELEPHAS MAXIMUS)
      INFECTED WITH MYCOBACTERIUM TUBERCULOSIS.
AB  - This report describes the pharmacokinetic profiles of chronically administered
      oral isoniazid and rifampin in one adult male and one adult female Asian elephant
      ( Elephas maximus ) that were asymptomatically infected with Mycobacterium
      tuberculosis . Rifampin's half-life was reduced when compared to previous single
      dose pharmacokinetic profiles of healthy uninfected Asian elephants. Both
      elephants experienced delayed absorption of isoniazid and rifampin as compared to
      previous pharmacokinetic studies in this species. The altered pharmacokinetics of
      both drugs in repeated-dosing clinical situations underscores the need for
      individual therapeutic drug monitoring for tuberculosis treatment.

PMID- 27691968
TI  - EFFECTS OF EXERCISE ON THE PLASMA LIPID PROFILE IN HISPANIOLAN AMAZON PARROTS
      (AMAZONA VENTRALIS) WITH NATURALLY OCCURRING HYPERCHOLESTEROLEMIA.
AB  - Hypercholesterolemia is common in psittacines, and Amazon parrots ( Amazona spp.)
      are particularly susceptible. Associations have been demonstrated between
      naturally occurring and experimentally induced hypercholesterolemia and
      atherosclerosis in psittacines. Daily exercise improves lipid metabolism in
      humans and other mammals, as well as pigeons and chickens, under varying
      experimental conditions. Hispaniolan Amazon parrots ( Amazona ventralis ) with
      naturally occurring hypercholesterolemia (343-576 mg/dl) were divided into two
      groups. An exercised group (n = 8) was housed as a flock and exercised daily with
      30 min of aviary flight and 30 min walking on a rotating perch. A sedentary
      control group (n = 4) was housed in individual cages with no exercise regime. A
      plasma lipid panel, including total cholesterol, high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglycerides, was
      validated for this species. Body weight, chest girth, and the lipid panel were
      measured at 0, 61, and 105 days. Hematology and plasma biochemistry were measured
      at 0 and 105 days. Weight and girth were significantly lower in exercised than
      sedentary parrots at 61 and 105 days. HDL-C concentrations were significantly
      higher in exercised parrots at 61 days but returned to near baseline by 105 days.
      There were no significant changes in hematology, biochemistry, or other lipid
      panel parameters. Results were similar to studies in humans and animal models, in
      which increased HDL-C was the most consistent effect of exercise on circulating
      lipid and lipoprotein parameters. The return toward baseline HDL-C may have
      resulted from decreased participation in aviary flight. Additional investigation
      will be required to determine the amount of exercise and change in circulating
      lipid-related parameters necessary to improve long-term wellness in psittacine
      species predisposed to hypercholesterolemia.

PMID- 27691969
TI  - MEDICAL MANAGEMENT OF RECURRENT EOSINOPHILIC GRANULOMA IN TWO BLACK RHINOCEROS
      (DICEROS BICORNIS).
AB  - Recurrent eosinophilic granuloma (EG) in two captive eastern black rhinoceros (
      Diceros bicornis michaeli) was effectively managed with glucocorticoids and
      antihistamines. The first case was a female and the second case was a male. The
      animals were housed at separate institutions and initially presented with
      hemorrhagic oral lesions. Multifocal lesions occurred in the second case.
      Multiple biopsies were taken from each animal, all of which were consistent with
      EG. Each animal was anesthetized multiple times for surgical treatment but
      experienced frequent recurrence. Due to lack of response to therapy and the risks
      and adverse events associated with repeated anesthesia, medical treatment was
      initiated in both cases using a tapering dose of oral dexamethasone. The lesions
      dramatically improved, but would recur frequently after treatment. Hydroxyzine,
      an oral antihistamine, greatly reduced the incidence and severity of the lesions.
      Medical management with glucocorticoids and antihistamines minimized stressful
      anesthetic events in both cases and contributed to the successful management of
      this recurrent disease. The exact pathogenesis of EG in black rhinoceros remains
      unknown but response to antihistamines suggests an allergic etiology.

PMID- 27691970
TI  - MYOSITIS OSSIFICANS TRAUMATICA IN A VAMPIRE BAT (DESMODUS ROTUNDUS).
AB  - A 15-yr-old sexually intact female vampire bat ( Desmodus rotundus ) was
      diagnosed with myositis ossificans traumatica of the abdominal wall. The bat
      presented with a large ulcerated firm mass along the abdomen. Radiographs and
      cytology were performed, followed by surgical exploration. The mass was
      determined to be nonresectable and the bat was euthanized. Histopathology showed
      severe necrotizing, degenerative, and pyogranulomatous myositis with osseous and
      cartilaginous metaplasia, fibrosis, and ulceration, which were consistent with
      myositis ossificans traumatica. Myositis ossificans traumatica is commonly
      associated with previous trauma to skeletal muscle. Two years prior, this bat had
      an emergency Caesarian section at this site, which was postulated to elicit a
      marked tissue response leading to this condition. Myositis ossificans traumatica
      is infrequently reported in humans, dogs, cats, pigs, and horses. To the author's
      knowledge, this is the first report of this condition in a bat.

PMID- 27691971
TI  - SYSTEMIC BLASTOMYCOSIS IN A CAPTIVE RED RUFFED LEMUR (VARECIA RUBRA).
AB  - A 5-yr-old, intact male red ruffed lemur ( Varecia rubra ) presented for
      evaluation as the result of a 1-wk history of lethargy and hyporexia. Physical
      examination findings included thin body condition, muffled heart sounds, harsh
      lung sounds, and liquid brown diarrhea. Complete blood count and serum
      biochemistry showed an inflammatory leukogram, mild hyponatremia, and mild
      hypochloremia. Orthogonal trunk radiographs revealed a severe alveolar pattern in
      the right cranial lung lobes with cardiac silhouette effacement. Thoracic
      ultrasound confirmed a large, hypoechoic mass in the right lung lobes. Fine
      needle aspiration of the lung mass and cytology revealed fungal yeast organisms,
      consistent with Blastomyces dermatitidis. Blastomyces Quantitative EIA Test on
      urine was positive. Postmortem examination confirmed systemic blastomycosis
      involving the lung, tracheobronchial lymph nodes, spleen, kidney, liver,
      cerebrum, and eye. To the authors' knowledge, this is the first report of
      blastomycosis in a prosimian species.

PMID- 27691972
TI  - SURGICAL CORRECTION OF TRAUMATIC PATELLAR LUXATION IN AN EURASIAN LYNX (LYNX
      LYNX).
AB  - The aim of this report is to describe the successful surgical repair of a
      traumatic medial patellar luxation in a 4-yr-old female Eurasian lynx ( Lynx lynx
      ). The animal presented with hind limb lameness. Physical and radiographic
      examinations were performed under sedation. After diagnosing a medial patellar
      luxation, surgical repair was recommended. A combination of soft tissue
      reconstructive techniques was used to repair the medial patellar luxation. The
      limb was not immobilized postoperatively, but the animal was confined to a cage
      for 1 mo. The recovery was uneventful and return to normal activity was observed
      within 1 mo. Soft tissue reconstructive techniques can be used as the only
      surgical treatment for the repair of a traumatic patellar luxation in both
      domestic and wild animals.

PMID- 27691973
TI  - XENOTRANSFUSION IN AN ISLAND FOX (UROCYON LITTORALIS CLEMENTAE) USING BLOOD FROM
      A DOMESTIC DOG (CANIS LUPUS FAMILIARIS).
AB  - Successful xenotransfusion in an island fox ( Urocyon littoralis clementae) has
      not been previously reported but may be necessary in an emergency. An 11-yr-old
      male, intact, captive island fox was exhibiting clinical signs of rattlesnake
      envenomation including hypoperfusion, tachypnea, facial edema, and multifocal
      facial and cervical ecchymosis. Blood work revealed severe thrombocytopenia (18
      K/MUl) and anemia (Hct 15.8%). A presumptive diagnosis of rattlesnake ( Crotalus
      sp.) envenomation was made. Initial treatment included oxygen therapy, fluid
      therapy, antibiotics, antacids, pain medications, and polyvalent crotalid anti
      venom. Emergency xenotransfusion using whole blood (45 ml) from a domestic dog
      was used due to worsening clinical signs from anemia. No acute or delayed
      transfusion reactions were observed in the fox and the patient made a full
      recovery 5 days later. Successful xenotransfusion in an island fox using whole
      blood from a domestic dog ( Canis lupus familiaris) is possible and may be
      lifesaving.

PMID- 27691974
TI  - ESTABLISHMENT OF A FIBRINOGEN REFERENCE INTERVAL IN ORNATE BOX TURTLES (TERRAPENE
      ORNATA ORNATA).
AB  - This study sought to establish a reference interval for fibrinogen in healthy
      ornate box turtles ( Terrapene ornata ornata). A total of 48 turtles were
      enrolled, with 42 turtles deemed to be noninflammatory and thus fitting the
      inclusion criteria and utilized to estimate a fibrinogen reference interval.
      Turtles were excluded based upon physical examination and blood work
      abnormalities. A Shapiro-Wilk normality test indicated that the noninflammatory
      turtle fibrinogen values were normally distributed (Gaussian distribution) with
      an average of 108 mg/dl and a 95% confidence interval of the mean of 97.9-117
      mg/dl. Those turtles excluded from the reference interval because of
      abnormalities affecting their health had significantly different fibrinogen
      values (P = 0.313). A reference interval for healthy ornate box turtles was
      calculated. Further investigation into the utility of fibrinogen measurement for
      clinical usage in ornate box turtles is warranted.

PMID- 27691975
TI  - HEPATIC OSTEODYSTROPHY IN A GOLDEN LION TAMARIN (LEONTOPITHECUS ROSALIA).
AB  - An 8-yr-old, captive, female golden lion tamarin ( Leontopithecus rosalia ) with
      a 6-yr history of hyperbilirubinemia was examined for inappetence and weight
      loss. Physical examination and blood pressure monitoring under anesthesia
      revealed hypothermia and hypotension, and blood work revealed hypoglycemia,
      markedly elevated liver enzymes, including serum alkaline phosphatase, aspartate
      aminotransferase, and alanine aminotransferase, and confirmed the
      hyperbilirubinemia. A complete blood count suggested chronic lymphoid leukemia.
      The animal's condition deteriorated during recovery, and the animal died despite
      aggressive treatment. Grossly, there was micronodular cirrhosis of the liver,
      severe icterus, and diffuse osteopenia of all examined bones. Microscopic
      examination of the liver confirmed the micronodular cirrhosis and bone lesions
      were compatible with diffuse osteopenia and osteomalacia. This brief
      communication presents a case of chronic liver disease and lesions indicative of
      metabolic bone disease, also known as hepatic osteodystrophy. To the authors'
      knowledge, this is the first documented case of hepatic osteodystrophy in the
      veterinary literature.

PMID- 27691976
TI  - NEPHROPATHIES IN THE EUROPEAN CAPTIVE CHEETAH (ACINONYX JUBATUS) POPULATION.
AB  - According to previous studies in captive cheetah ( Acinonyx jubatus )
      populations, one of the most threatening diseases besides amyloidosis,
      myelopathy, veno occlusive disease, and gastritis, is renal failure. Contrary to
      captive cheetahs in North America and South Africa, morphological data concerning
      renal lesions in the cheetah European Endangered Species Program (EEP) are
      lacking. This study details the histological characterization as well as
      immunohistochemical and morphometrical analysis of nephropathies in 35 captive
      cheetahs from the EEP, which were necropsied between 1985 and 2003. Examination
      of paraffin- and glycolmethacrylate-methylmethacrylate (GMA-MMA) embedded kidney
      samples by light microscopy revealed glomerulonephritis in 91%, with a high
      prevalence for glomerulosclerosis and glomerulonephritis with the histologic
      pattern of membranous glomerulonephritis (77%). Besides these predominating
      glomerulopathies, a wide range of other renal lesions, like acute tubular
      necrosis, interstitial nephritis, calcinosis, and amyloidosis, were present.
      Pathological expression of collagen type IV, complement C3, fibronectin, and IgG
      was demonstrated in the glomeruli of the cheetah kidneys with the use of the
      avidin-biotin complex method. Morphometrical analysis was performed on GMA-MMA
      embedded kidney samples to obtain glomerulosclerosis index and glomerulosclerosis
      incidence.

PMID- 27691977
TI  - A SYSTEMATIC REVIEW OF THE LITERATURE RELATING TO CAPTIVE GREAT APE MORBIDITY AND
      MORTALITY.
AB  - Wild bonobos (Pan paniscus), chimpanzees (Pan troglodytes), Western gorillas
      (Gorilla gorilla), and orangutans (Pongo pygmaeus, Pongo abelii) are threatened
      with extinction. In order to help maintain a self-sustaining zoo population,
      clinicians require a sound understanding of the diseases with which they might be
      presented. To provide an up-to-date perspective on great ape morbidity and
      mortality, a systematic review of the zoological and veterinary literature of
      great apes from 1990 to 2014 was conducted. This is the first review of the great
      ape literature published since 1990 and the first-ever systematic literature
      review of great ape morbidity and mortality. The following databases were
      searched for relevant articles: CAB Abstracts, Web of Science Core Collection,
      BIOSIS Citation Index, BIOSIS Previews, Current Contents Connect, Data Citation
      Index, Derwent Innovations Index, MEDLINE, SciELO Citation Index, and Zoological
      Record. A total of 189 articles reporting on the causes of morbidity and
      mortality among captive great apes were selected and divided into comparative
      morbidity-mortality studies and case reports-series or single-disease prevalence
      studies. The content and main findings of the morbidity-mortality studies were
      reviewed and the main limitations identified. The case reports-case series and
      single-disease prevalence studies were categorized and coded according to taxa,
      etiology, and body system. Subsequent analysis allowed the amount of literature
      coverage afforded to each category to be calculated and the main diseases and
      disorders reported within the literature to be identified. This review concludes
      that reports of idiopathic and infectious diseases along with disorders of the
      cardiovascular, respiratory, and gastrointestinal body systems were particularly
      prominent within the great ape literature during 1990-2014. However, recent and
      accurate prevalence figures are lacking and there are flaws in those reviews that
      do exist. There is therefore a critical need for a robust, widespread, and more
      up-to-date review of mortality among captive great apes.

PMID- 27691978
TI  - The Role of microRNA in Ischemic and Hemorrhagic Stroke.
AB  - BACKGROUND: Stroke is the second leading cause of death worldwide. Understanding
      of gene expression dynamics could bring new approaches in diagnostics and therapy
      of stroke. Small noncoding molecules termed "microRNA" represent the most
      flexible network of gene expression regulators. METHOD: The aim of this review
      was to briefly describe the structure and function of microRNA and summarize the
      current knowledge about the involvement of microRNAs in the pathophysiology of
      ischemic and hemorrhagic stroke based on both experimental and clinical studies.
      RESULTS: Numerous profiling studies identified candidate microRNAs and partially
      described dynamics of their expression after the stroke. However, complex
      associations of specific microRNAs expression with main clinical characteristics
      and deeper insight into mechanisms of their regulatory functions are still
      missing. In this review, we put special emphasis on several microRNA clusters
      involved in neuroprotection (miR-124, miR-181, miR-21, miR-29, miR-210 and let7).
      Potential application of microRNAs as biomarkers and diagnostic or therapeutic
      targets was also discussed. CONCLUSION: Full understanding of the regulatory
      mechanisms of the microRNA networks represents a novel direction for stroke
      research. To date, we do not have effective tools to control pathophysiological
      processes associated with stroke. Thus the microRNAs have to be considered as a
      very promising target for future stroke therapies.

PMID- 27691980
TI  - Why is the topic of the biological embedding of experiences important for
      translation?
AB  - Translational research focuses on innovation in healthcare settings, but this is
      a two-way process that may have implications for either treatment or prevention.
      Smoking and lung cancer and the fetal alcohol syndrome are used as examples.
      Experimental medicine that budges basic and clinical science often constitutes a
      key way forward. Areas of scientific progress and challenge are discussed in
      relation to drug action, social cognition, cognitive neuroscience, molecular
      genetics, gene-environment interaction, and epigenetics. Key concepts and
      challenges in relation to stress include toxicity, allostatic load, the
      hypothalamus-pituitary-adrenal axis, and objectives versus subjective stress. The
      reasons for the need to test causal inferences are discussed. Various kinds of
      "natural experiments" are discussed in illustration using the assisted conception
      design, the discordant monozygotic twin design, and the study of universal
      exposure. Animal models are discussed in relation to enrichment and deprivation
      effects and the effects of infant separation experiences, epigenetic effects, and
      the biological embedding of experiences. Translational issues are discussed in
      relation to the hypothalamic-pituitary-adrenal axis, epigenetics, and
      inflammation. In conclusion, it is suggested that there are immediate
      possibilities for experimental medicine but caution is needed with respect to
      moving into translation too quickly.

PMID- 27691979
TI  - An investigation of child maltreatment and epigenetic mechanisms of mental and
      physical health risk.
AB  - In the present investigation, differential methylation analyses of the whole
      genome were conducted among a sample of 548 school-aged low-income children
      (47.8% female, 67.7% Black, M age = 9.40 years), 54.4% of whom had a history of
      child maltreatment. In the context of a summer research camp, DNA samples via
      saliva were obtained. Using GenomeStudio, Methylation Module, and the Illumina
      Custom Model, differential methylation analyses revealed a pattern of greater
      methylation at low methylation sites (n = 197 sites) and medium methylation sites
      (n = 730 sites) and less methylation at high methylation sites (n = 907 sites)
      among maltreated children. The mean difference in methylation between the
      maltreated and nonmaltreated children was 6.2%. The relative risk of maltreatment
      with known disease biomarkers was also investigated using GenoGo MetaCore
      Software. A large number of network objects previously associated with mental
      health, cancer, cardiovascular systems, and immune functioning were identified
      evidencing differential methylation among maltreated and nonmaltreated children.
      Site-specific analyses were also conducted for aldehyde dehydrogenase 2 (ALDH2),
      ankyrin repeat and kinase domain containing 1 (ANKK1), and nuclear receptor
      subfamily 3, group C, member 1 (NR3C1) genes, and the results highlight the
      importance of considering gender and the developmental timing of maltreatment.
      For ALDH2, the results indicated that maltreated girls evidenced significantly
      lower methylation compared to nonmaltreated girls, and maltreated boys evidenced
      significantly higher methylation compared to nonmaltreated boys. Moreover, early
      onset-not recently maltreated boys evidenced significantly higher methylation at
      ALDH2 compared to nonmaltreated boys. Similarly, children with early onset
      nonrecent maltreatment evidenced significantly higher methylation compared to
      nonmaltreated children at ANKK1. The site-specific results were not altered by
      controlling for genotypic variation of respective genes. The findings demonstrate
      increased risk for adverse physical and mental health outcomes associated with
      differences in methylation in maltreated children and indicate differences among
      maltreated children related to developmental timing of maltreatment and gender in
      genes involved in mental health functioning.

PMID- 27691982
TI  - Epigenetic regulation of cognition: A circumscribed review of the field.
AB  - The last decade has been marked by an increased interest in relating epigenetic
      mechanisms to complex human behaviors, although this interest has not been
      balanced, accentuating various types of affective and primarily ignoring
      cognitive functioning. Recent animal model data support the view that epigenetic
      processes play a role in learning and memory consolidation and help transmit
      acquired memories even across generations. In this review, we provide an overview
      of various types of epigenetic mechanisms in the brain (DNA methylation, histone
      modification, and noncoding RNA action) and discuss their impact proximally on
      gene transcription, protein synthesis, and synaptic plasticity and distally on
      learning, memory, and other cognitive functions. Of particular importance are
      observations that neuronal activation regulates the dynamics of the epigenome's
      functioning under precise timing, with subsequent alterations in the gene
      expression profile. In turn, epigenetic regulation impacts neuronal action,
      closing the circle and substantiating the signaling pathways that underlie, at
      least partially, learning, memory, and other cognitive processes.

PMID- 27691983
TI  - Can Fecal Microbiota Transplantation (FMT) Eradicate Fecal Colonization With
      Vancomycin-Resistant Enterococci (VRE)?

PMID- 27691981
TI  - Testing the biological embedding hypothesis: Is early life adversity associated
      with a later proinflammatory phenotype?
AB  - Accumulating evidence suggests that the experience of early life adversity is a
      risk factor for a range of poor outcomes across development, including poor
      physical health in adulthood. The biological embedding model of early adversity
      (Miller, Chen, & Parker, 2011) suggests that early adversity might become
      embedded within immune cells known as monocytes/macrophages, programming them to
      be overly aggressive to environmental stimuli and insensitive to inhibitory
      signals, creating a "proinflammatory phenotype" that increases vulnerability to
      chronic diseases across the life span. We tested this hypothesis in the present
      study. Adolescent girls (n = 147) had blood drawn every 6 months across a 2.5
      year period. To assess inflammatory responses to challenge, their monocytes were
      stimulated in vitro with a bacterial product, and production of the cytokine
      interleukin-6 was quantified. Hydrocortisone was added to cultures to assess the
      cells' sensitivity to glucocorticoids' anti-inflammatory signal. Using cluster
      analyses, we found that early life adversity was associated with greater odds of
      displaying a proinflammatory phenotype characterized by relatively larger
      interleukin-6 responses and relatively less sensitivity to glucocorticoids. In
      contrast, ongoing social stress was not associated with increasing odds of being
      categorized in the proinflammatory cluster. These findings suggest that early
      life adversity increases the probability of developing a proinflammatory
      phenotype, which, if sustained, could forecast risk for health problems later in
      life.

PMID- 27691984
TI  - Increase in Prevalence of KPC-2-Producing Klebsiella pneumoniae Recovered From
      Respiratory Secretions of Intensive Care Patients-Getting a Free Ride on a
      Menacing Colistin Resistance.

PMID- 27691986
TI  - An Evaluation of Food as a Potential Source for Clostridium difficile Acquisition
      in Hospitalized Patients.
AB  - OBJECTIVE To determine whether Clostridium difficile is present in the food of
      hospitalized patients and to estimate the risk of subsequent colonization
      associated with C. difficile in food. METHODS This was a prospective cohort study
      of inpatients at a university-affiliated tertiary care center, May 9, 2011-July
      12, 2012. Enrolled patients submitted a portion of food from each meal. Patient
      stool specimens and/or rectal swabs were collected at enrollment, every 3 days
      thereafter, and at discharge, and were cultured for C. difficile. Clinical data
      were reviewed for evidence of infection due to C. difficile. A stochastic,
      discrete event model was developed to predict exposure to C. difficile from food,
      and the estimated number of new colonization events from food exposures per 1,000
      admissions was determined. RESULTS A total of 149 patients were enrolled and 910
      food specimens were obtained. Two food specimens from 2 patients were positive
      for C. difficile (0.2% of food samples; 1.3% of patients). Neither of the 2
      patients was colonized at baseline with C. difficile. Discharge colonization
      status was available for 1 of the 2 patients and was negative. Neither was
      diagnosed with C. difficile infection while hospitalized or during the year
      before or after study enrollment. Stochastic modeling indicated contaminated
      hospital food would be responsible for less than 1 newly colonized patient per
      1,000 hospital admissions. CONCLUSIONS The recovery of C. difficile from the food
      of hospitalized patients was rare. Modeling suggests hospital food is unlikely to
      be a source of C. difficile acquisition. Infect Control Hosp Epidemiol 2016;1401
      1407.

PMID- 27691988
TI  - QUALITY OF HEALTH TECHNOLOGY ASSESSMENT REPORTS PREPARED FOR THE MEDICAL SERVICES
      ADVISORY COMMITTEE.
AB  - OBJECTIVES: The Medical Services Advisory Committee (MSAC) makes recommendations
      to the Australian Government for funding health technologies under the Medicare
      Benefits Schedule (MBS). Differences in public, clinical, commercial, and
      political opinions on health expenditure emphasize the importance of defensible
      funding decisions. We aimed to evaluate the quality of health technology
      assessment (HTA) reports over time and among health technologies assessed for
      MSAC. MAIN OUTCOME MEASURES: A cohort study was performed of HTA reports prepared
      for MSAC between 1998 and 2013. We measured the quality of HTA reports using
      reporting guidelines proposed by the European Collaboration for Assessment of
      Health Interventions. Individual component scores across eleven domains were
      calculated, and summed for an overall aggregate score. We used linear regression
      to investigate any change in quality over time and among the types of
      technologies assessed. RESULTS: We included 110 HTA reports. The safety (80
      percent), effectiveness (84 percent), economic (74 percent), and organizational
      (99 percent) domains were better reported than the psychological, social, and
      ethical considerations (34 percent). The basic (75 percent), methodological (62
      percent), background (82 percent), contextual (46 percent), status quo (54
      percent), and technical information (66 percent) that framed each assessment were
      inconsistently reported. On average, overall quality scores increased by 2
      percent (p < 0.001) per year, from approximately 60 percent to 80 percent over
      the 15-year period, with no significant difference among surgical, diagnostic or
      other nonpharmaceutical health technologies (p = 0.22). CONCLUSIONS: HTA reports
      prepared for MSAC are a key tool in allocating scarce health resources. The
      overall quality of these reports has improved, but the reporting of specific
      domains and subthemes therein could be better addressed.

PMID- 27691987
TI  - Claw disorders in dairy cattle - an unexpected association between energy
      metabolism and sole haemorrhages.
AB  - The present study investigated whether changes of energy metabolism post-partum
      (pp) are associated with claw health. For this purpose, back-fat-thickness (BFT)
      was measured and blood samples were taken from 146 cows at four examination
      times. The serum levels of free fatty acids (FFA), beta-hydroxybutyrate (BHB) and
      glucose were measured. Furthermore, in the first week postpartum (pp) and at 8
      weeks pp, a claw trimming was done and the presence and extent of sole
      haemorrhages (SH) was recorded. Animals with high BFT at calving and therefore
      high fat mobilisation and whose FFA and BHB levels in the first week pp exceeded
      the reference values had fewer pathological changes of the claws than thinner
      animals whose FFA and BHB levels stayed within reference ranges. The body
      condition before calving, represented in this study by BFT, plays an important
      role in non-infectious claw disorders. Poorer body condition was found to be
      associated with the SH that develop in the first 2 months of lactation.

PMID- 27691985
TI  - Childhood adversity and epigenetic regulation of glucocorticoid signaling genes:
      Associations in children and adults.
AB  - Early childhood experiences have lasting effects on development, including the
      risk for psychiatric disorders. Research examining the biologic underpinnings of
      these associations has revealed the impact of childhood maltreatment on the
      physiologic stress response and activity of the hypothalamus-pituitary-adrenal
      axis. A growing body of literature supports the hypothesis that environmental
      exposures mediate their biological effects via epigenetic mechanisms.
      Methylation, which is thought to be the most stable form of epigenetic change, is
      a likely mechanism by which early life exposures have lasting effects. We present
      recent evidence related to epigenetic regulation of genes involved in
      hypothalamus-pituitary-adrenal axis regulation, namely, the glucocorticoid
      receptor gene (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) and FK506
      binding protein 51 gene (FKBP5), after childhood adversity and associations with
      risk for psychiatric disorders. Implications for the development of interventions
      and future research are discussed.

PMID- 27691990
TI  - TESTING MULTI-CRITERIA DECISION ANALYSIS FOR MORE TRANSPARENT RESOURCE-ALLOCATION
      DECISION MAKING IN COLOMBIA.
AB  - OBJECTIVES: In 2012, Colombia experienced an important institutional
      transformation after the establishment of the Health Technology Assessment
      Institute (IETS), the disbandment of the Regulatory Commission for Health and the
      reassignment of reimbursement decision-making powers to the Ministry of Health
      and Social Protection (MoHSP). These dynamic changes provided the opportunity to
      test Multi-Criteria Decision Analysis (MCDA) for systematic and more transparent
      resource-allocation decision-making. METHODS: During 2012 and 2013, the MCDA
      framework Evidence and Value: Impact on Decision Making (EVIDEM) was tested in
      Colombia. This consisted of a preparatory stage in which the investigators
      conducted literature searches and produced HTA reports for four interventions of
      interest, followed by a panel session with decision makers. This method was
      contrasted with a current approach used in Colombia for updating the publicly
      financed benefits package (POS), where narrative health technology assessment
      (HTA) reports are presented alongside comprehensive budget impact analyses
      (BIAs). RESULTS: Disease severity, size of population, and efficacy ranked at the
      top among fifteen preselected relevant criteria. MCDA estimates of technologies
      of interest ranged between 71 to 90 percent of maximum value. The ranking of
      technologies was sensitive to the methods used. Participants considered that a
      two-step approach including an MCDA template, complemented by a detailed BIA
      would be the best approach to assist decision-making in this context.
      Participants agreed that systematic priority setting should take place in
      Colombia. CONCLUSIONS: This work may serve as the basis to the MoHSP on its
      interest of setting up a systematic and more transparent process for resource
      allocation decision-making.

PMID- 27691989
TI  - Comparison of Data Collection for Healthcare-Associated Infection Surveillance in
      Nursing Homes.
AB  - OBJECTIVE To facilitate surveillance and describe the burden of healthcare
      associated infection (HAI) in nursing homes (NHs), we compared the quality of
      resident-level data collected by NH personnel and external staff. DESIGN A 1-day
      point-prevalence survey SETTING AND PARTICIPANTS Overall, 9 nursing homes among 4
      Centers for Disease Control and Prevention (CDC) Emerging Infection Program (EIP)
      sites were included in this study. METHODS NH personnel collected data on
      resident characteristics, clinical risk factors for HAIs, and the presence of 3
      HAI screening criteria on the day of the survey. Trained EIP surveillance
      officers collected the same data elements via retrospective medical chart review
      for comparison; surveillance officers also collected available data to identify
      HAIs (using revised McGeer definitions). Overall agreement was calculated among
      residents identified by both teams with selected risk factors and HAI screening
      criteria. The impact of using NH personnel to collect screening criteria on HAI
      prevalence was assessed. RESULTS The overall prevalence of clinical risk factors
      among the 1,272 residents was similar between NH personnel and surveillance
      officers, but the level of positive agreement (residents with factors identified
      by both teams) varied between 39% and 87%. Surveillance officers identified 253
      residents (20%) with >=1 HAI screening criterion, resulting in 67 residents with
      an HAI (5.3 per 100 residents). The NH personnel identified 152 (12%) residents
      with >=1 HAI screening criterion; 42 residents had an HAI (3.5 per 100
      residents). CONCLUSION We identified discrepancies in resident-level data
      collection between surveillance officers and NH personnel, resulting in varied
      estimates of the HAI prevalence. These findings have important implications for
      the design and implementation of future HAI prevalence surveys. Infect Control
      Hosp Epidemiol 2016;1440-1445.

PMID- 27691991
TI  - Haplotypic variation in the UCP1 gene is associated with milk traits in dairy
      cows.
AB  - Uncoupling protein-1 (UCP1) plays a role in the regulation of body temperature,
      metabolic rate and energy expenditure in animals. While variation in UCP1 and its
      phenotypic effect has been investigated in humans and sheep, little is known
      about this gene in cattle. In this study, four regions of bovine UCP1 were
      investigated in 612 Holstein-Friesian * Jersey (HF * J) dairy cows using
      polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP)
      analyses. In the four regions of the gene analysed, a total of 13 SNPs were
      detected. Three sequences (a, b and c) were found in Region-2 and three sequences
      (A, B and C) were found in Region-4, and these were assembled into three (a-B, b
      B and c-A) common and three (b-C, c-B and c-C) rare haplotypes. Of the three
      common haplotypes, b-B and c-A were associated (P < 0.007 and P < 0.043,
      respectively) with increased milk yield and tended to be associated (P < 0.085
      and P < 0.070, respectively) with decreased fat percentage. Cows with genotype b
      B/a-B produced more milk (P < 0.004), but with a lower percentage of fat (P <
      0.035) and protein (P < 0.038) than cows with genotype a-B/a-B. Cows of genotype
      a-B/c-A had milk of low fat percentage (P < 0.017), but tended to produce more
      milk (P < 0.059) than cows of genotype a-B/a-B. This suggests that UCP1 affects
      milk yield, milk fat percentage and milk protein percentage.

PMID- 27691992
TI  - EARLY COST-EFFECTIVENESS ANALYSIS OF NEW MEDICAL TESTS: RESPONSE.
AB  - As strong advocates and adopters of early cost-effectiveness modeling for test
      evaluation, we were excited to see the recent article "The Early Bird Catches the
      Worm: Early Cost-Effectiveness Analysis of New Medical Tests," in which Buisman
      and colleagues present a succinct and generalizable framework for conducting this
      type of analysis. The authors have done an excellent job in identifying and
      summarizing the key components of this methodology, as well as highlighting
      fundamental differences between early analyses versus the traditional late-stage
      approach. As the number of medical tests coming to market continues to grow,
      there is an ever growing need to develop rigorous methodology in this area, and
      we commend the authors for this timely work.

PMID- 27691993
TI  - EMERGENCE OF "DRIVERS" FOR THE IMPLEMENTATION OF HEALTH TECHNOLOGY ASSESSMENT.
AB  - BACKGROUND: Health technology assessment (HTA) examines the consequences of the
      application of health technologies and is aimed at better informing decision
      makers. Over the past 30 years, different countries have implemented HTA
      organizations. Colombia established by law its own HTA agency (IETS) in 2011
      which started operations in November 2012. The aim of this study was to assess
      the feasibility of conducting and using HTA to inform decision-making in this
      context. Through a qualitative approach, ten "drivers" emerged with the ability
      to help or hinder HTA development in this context: availability and quality of
      data, implementation strategy, cultural aspects, local capacity, financial
      support, policy/political support, globalization, stakeholder pressure, health
      system context, and usefulness perception. METHODS: Semi-structured interviews
      were conducted with key HTA researchers, after following rigorous transcription,
      and thematic content analysis, those aspects that may be barriers or facilitator
      for HTA development and use in Colombia were identified. RESULTS: Although HTA
      has become a tool to inform decision-making around the world, its use may vary
      according to setting. Determining those aspects which may enable or interfere
      with HTA development and use in Colombia may be useful for other countries when
      considering the establishment of HTA systems. CONCLUSIONS: The conceptual
      transferability of concepts like "drivers" with caveats may be of interest for
      similar settings trying to incorporate HTA processes and institutions into
      systematic decision-making.

PMID- 27691994
TI  - Determinants of Engagement in Leisure-time Physical Activity - Dialogue with
      Senior Athletes.
AB  - This article explores the factors determining whether older adults engage in the
      Senior Games and related leisure-time physical activity through examining the
      adults' salient beliefs. We conducted 10 in-depth interviews with older adults
      who have participated in the Senior Games. Underpinned by the planned behavior
      theory's framework, we explored three types of beliefs: advantages and
      disadvantages (behavioral beliefs), social support and pressure (normative
      beliefs), and facilitators and impediments (control beliefs). Interview
      respondents were found to engage in the Senior Games and related physical
      activity to the extent that they associated various intangible advantages with
      the games and valued psychological satisfaction. They viewed their peers and
      families as supporting and approving of their engagement and recognized the
      physical capabilities required, and structural constraints necessary, to engage
      in the games and related activity. With these findings, pertinent beliefs can be
      combined with interventions designed to encourage leisure-time physical
      activities by older adults.

PMID- 27691996
TI  - Variation of milk coagulation properties, cheese yield, and nutrients recovery in
      curd of cows of different breeds before, during and after transhumance to
      highland summer pastures.
AB  - This paper aimed at evaluating the effect of summer transhumance to mountain
      pastures of dairy cows of different breeds on cheese-making ability of milk. Data
      were from 649 dairy cows of specialized (Holstein Friesian and Brown Swiss) dual
      purpose (Simmental) and local (mostly Rendena and Alpine Grey) breeds. The
      Fourier-Transform Infra-Red Spectra (FTIRS) of their milk samples were collected
      before and after transhumance in 109 permanent dairy farms, and during
      transhumance in 14 summer farms (with multi-breeds herds) of the Trento Province,
      north-eastern Italy. A variety of 18 traits describing milk coagulation, curd
      firming, cheese yield and nutrients recovery in curd/loss in whey were predicted
      on the basis of FTIRS collected at the individual cow level. Moving the cows to
      summer farms improved curd firming traits but reduced cheese yields because of an
      increase of water and fat lost in the whey. During summer grazing, most of cheese
      making traits improved, often non-linearly. The milk from summer farms
      supplementing cows with more concentrates showed better curd firming and cheese
      yield, because of lower fat lost in the whey. The breed of cows affected almost
      all the traits with a worst cheese-making ability for milk samples of Holsteins
      through all the trial, and interacted with concentrate supplementation because
      increasing compound feed tended to improve cheese-making traits for all breed,
      with the exception of local breeds for coagulation time and of Brown Swiss for
      curd firming time. In general, summer transhumance caused a favourable effect on
      cheese-making aptitude of milk, even though with some difference according to
      parity, initial days in milk, breed and concentrate supplementation of cows.

PMID- 27691995
TI  - The presence of fever in adults with influenza and other viral respiratory
      infections.
AB  - We compared the rates of fever in adult subjects with laboratory-confirmed
      influenza and other respiratory viruses and examined the factors that predict
      fever in adults. Symptom data on 158 healthcare workers (HCWs) with a laboratory
      confirmed respiratory virus infection were collected using standardized data
      collection forms from three separate studies. Overall, the rate of fever in
      confirmed viral respiratory infections in adult HCWs was 23.4% (37/158). Rates
      varied by virus: human rhinovirus (25.3%, 19/75), influenza A virus (30%, 3/10),
      coronavirus (28.6%, 2/7), human metapneumovirus (28.6%, 2/7), respiratory
      syncytial virus (14.3%, 4/28) and parainfluenza virus (8.3%, 1/12). Smoking
      [relative risk (RR) 4.65, 95% confidence interval (CI) 1.33-16.25] and co
      infection with two or more viruses (RR 4.19, 95% CI 1.21-14.52) were significant
      predictors of fever. Fever is less common in adults with confirmed viral
      respiratory infections, including influenza, than described in children. More
      than 75% of adults with a viral respiratory infection do not have fever, which is
      an important finding for clinical triage of adult patients with respiratory
      infections. The accepted definition of 'influenza-like illness' includes fever
      and may be insensitive for surveillance when high case-finding is required. A
      more sensitive case definition could be used to identify adult cases,
      particularly in event of an emerging viral infection.

PMID- 27691997
TI  - Reproductive efficiency of the bethylid wasp Cephalonomia tarsalis: the
      influences of spatial structure and host density.
AB  - The parasitoid wasp Cephalonomia tarsalis (Ashmead) (Hymenoptera: Bethylidae) is
      commonly present in stored product facilities. While beneficial, it does not
      provide a high degree of biological pest control against its host, the saw
      toothed beetle Oryzaephilus surinamensis (L.) (Coleoptera: Silvanidae). A
      candidate explanation for poor host population suppression is that adult females
      interfere with each other's foraging and reproductive behavior. We used simple
      laboratory microcosms to evaluate such mutual interference in terms of its
      overall effects on offspring production. We varied the density of the hosts and
      also the spatial structure of the environment, via the extent of population sub
      division and the provision of different substrates. Production of C. tarsalis
      offspring was positively influenced by host density and by the isolation of
      females. With incomplete sub-division within microcosms offspring production was,
      in contrast, low and even zero. The provision of corrugated paper as a substrate
      enhanced offspring production and partially mitigated the effects of mutual
      interference. We recommend simple improvements to mass rearing practice and
      identify promising areas for further behavioral and chemical studies towards a
      better understanding of the mechanisms of mutual interference.

PMID- 27691999
TI  - Control of oxidation-reduction potential during Cheddar cheese ripening and its
      effect on the production of volatile flavour compounds.
AB  - In cheese, a negative oxidation-reduction (redox) potential is required for the
      stability of aroma, especially that associated with volatile sulphur compounds.
      To control the redox potential during ripening, redox agents were added to the
      salted curd of Cheddar cheese before pressing. The control cheese contained only
      salt, while different oxidising or reducing agents were added with the NaCl to
      the experimental cheeses. KIO3 (at 0.05, 0.1 and 1%, w/w) was used as the
      oxidising agent while cysteine (at 2%, w/w) and Na2S2O4 (at 0.05 and 0.1%, w/w)
      were used as reducing agents. During ripening the redox potential of the cheeses
      made with the reducing agents did not differ significantly from the control
      cheese (E h ~ -120 mV) while the cheeses made with 0.1 and 0.05% KIO3 had a
      significantly higher and positive redox potential in the first month of ripening.
      Cheese made with 1% KIO3 had positive values of redox potential throughout
      ripening but no starter lactic acid bacteria survived in this cheese; however,
      numbers of starter organisms in all other cheeses were similar. Principal
      component analysis (PCA) of the volatile compounds clearly separated the cheeses
      made with the reducing agents from cheeses made with the oxidising agents at 2
      month of ripening. Cheeses with reducing agents were characterized by the
      presence of sulphur compounds whereas cheeses made with KIO3 were characterized
      mainly by aldehydes. At 6 month of ripening, separation by PCA was less evident.
      These findings support the hypothesis that redox potential could be controlled
      during ripening and that this parameter has an influence on the development of
      cheese flavour.

PMID- 27691998
TI  - Characterisation of equine satellite cell transcriptomic profile response to beta
      hydroxy-beta-methylbutyrate (HMB).
AB  - beta-Hydroxy-beta-methylbutyrate (HMB) is a popular ergogenic aid used by human
      athletes and as a supplement to sport horses, because of its ability to aid
      muscle recovery, improve performance and body composition. Recent findings
      suggest that HMB may stimulate satellite cells and affect expressions of genes
      regulating skeletal muscle cell growth. Despite the scientific data showing
      benefits of HMB supplementation in horses, no previous study has explained the
      mechanism of action of HMB in this species. The aim of this study was to reveal
      the molecular background of HMB action on equine skeletal muscle by investigating
      the transcriptomic profile changes induced by HMB in equine satellite cells in
      vitro. Upon isolation from the semitendinosus muscle, equine satellite cells were
      cultured until the 2nd day of differentiation. Differentiating cells were
      incubated with HMB for 24 h. Total cellular RNA was isolated, amplified, labelled
      and hybridised to microarray slides. Microarray data validation was performed
      with real-time quantitative PCR. HMB induced differential expressions of 361
      genes. Functional analysis revealed that the main biological processes influenced
      by HMB in equine satellite cells were related to muscle organ development,
      protein metabolism, energy homoeostasis and lipid metabolism. In conclusion, this
      study demonstrated for the first time that HMB has the potential to influence
      equine satellite cells by controlling global gene expression. Genes and
      biological processes targeted by HMB in equine satellite cells may support HMB
      utility in improving growth and regeneration of equine skeletal muscle; however,
      the overall role of HMB in horses remains equivocal and requires further
      proteomic, biochemical and pharmacokinetic studies.

PMID- 27692001
TI  - Acetoacetic acid induces oxidative stress to inhibit the assembly of very low
      density lipoprotein in bovine hepatocytes.
AB  - Dairy cows with fatty liver or ketosis exhibit hyperketonemia, oxidative stress,
      and a low rate of very low density lipoprotein (VLDL) assembly, and there may be
      a potential link among these characteristics. Therefore, the objective of this
      study was to determine the effect of acetoacetic acid (AcAc) on the assembly of
      VLDL in cow hepatocytes. Cultured cow hepatocytes were treated with different
      concentrations of AcAc with or without N-acetylcysteine (NAC, an antioxidant).
      AcAc treatment decreased the mRNA expression and activities of antioxidant
      enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      (GSH-Px), and significantly increased malondialdehyde (MDA) content, indicative
      of oxidative stress. Furthermore, AcAc treatment significantly down-regulated the
      mRNA expression of apolipoprotein B100 (ApoB100), apolipoprotein E (ApoE), and
      low density lipoprotein receptor (LDLR), which thus decreased VLDL assembly and
      increased triglyceride (TG) accumulation in these bovine hepatocytes.
      Importantly, NAC relieved AcAc-induced oxidative stress and increased VLDL
      assembly. In summary, these results suggest that AcAc-induced oxidative stress
      affects the assembly of VLDL, which increases TG accumulation in bovine
      hepatocytes.

PMID- 27692000
TI  - Frequency of autoimmune disorders and autoantibodies in patients with
      neuromyelitis optica.
AB  - OBJECTIVE: The aim of this study was to report the frequency of autoimmune
      disorders and autoantibodies in 22 patients with neuromyelitis optica (NMO), as
      well as whether the seropositivity for autoantibodies differs between anti
      aquaporin 4 (AQP4) positive and AQP4 negative NMO patients. METHODS: Demographic,
      medical records, and a profile of autoantibodies were evaluated in 22 NMO
      patients, including AQP4, anti-thyroid-stimulating hormone receptor, antinuclear
      antibodies (ANA), anti-thyroperoxidase (anti-TPO), anti-thyroglobulin (anti-Tg),
      anti-double-stranded DNA, anti-neutrophil cytoplasmic, anti-cyclic citrullinate
      peptide, rheumatoid factor, anti-SSA/Ro, anti-SSB/La, anti-Smith antibodies (anti
      Sm), anti-ribonucleoprotein, anti-nucleosome, and anti-Scl70. Thyroid-stimulating
      hormone and free thyroxin were measured. RESULTS: The frequency of women was
      higher than men (95.5% vs. 4.5%) and 68.2% were Afro-Brazilians. Six (27.3%)
      patients presented other autoimmune disorders, such as Hashimoto thyroiditis
      (n=2), Graves' disease (n=1), juvenile idiopathic arthritis (n=1), systemic lupus
      erythematosus and systemic sclerosis (n=1), and Raynaud's phenomenon (n=1). The
      most frequent autoantibodies were anti-AQP4 (54.5%), anti-nucleosome (31.8%), ANA
      (27.3%), anti-TPO (22.7%), and anti-Tg (22.7%). Difference was not observed in
      the frequency of autoimmune disorders when the patients were compared according
      to their anti-AQP4 status. CONCLUSION: The results of the present study
      underscored that the NMO patients present high frequency of autoantibodies
      against cellular antigens and the presence of autoimmune disorders. Further
      studies with large number of NMO patients may contribute to advances in the
      understanding of NMO disease mechanisms.

PMID- 27692002
TI  - SURVEY OF SEXUAL ACTIVITY AND CONTRACEPTIVE USE AMONG UNMARRIED YOUNG SCHOOL AND
      COLLEGE DROP-OUTS IN A DEFINED NIGERIAN POPULATION.
AB  - This study sought to characterize sexual behaviour, contraceptive use and
      contributory upbringing factors among young people who had dropped out of school
      or college in a Nigerian setting. A community-based, cross-sectional sexual
      survey of 161 young people aged between 15 and 35 who had dropped out of school
      or college was performed in Ado-Ekiti, south-west Nigeria, in April 2015. One
      hundred and nineteen of the respondents (73.9%) had had sexual intercourse. Mean
      age at sexual debut was 19.08+/-3.5 years. Of those with sexual experience, 79
      (66.4%) had their sexual debut with a previous boy/girlfriend and 33 (27.7%) had
      it in their current relationship. Three (2.5%) respondents had first sex with a
      stranger. About 90% were still having sexual intercourse within 12 months of the
      survey; more males had had sex than females (81.1% versus 67.8%). Around 80% of
      those with sexual exposure practised a form of contraception, mainly use of the
      male condom, but fewer than 25% were all-time contraceptive users. Coming from a
      single-parent family (p=0.04) or from a family of poor economic status (AOR:
      7.41; 95% CI: 0.69-0.83) were found to be associated with sexual debut by the age
      of 19 and premarital sex, respectively, in these young people. Unprotected sexual
      intimacy was found to be high among young school/college drop-outs in this region
      of Nigeria. This group of young people need targeted reproductive health
      intervention as they represent a potent route for HIV transmission in the region.

PMID- 27692003
TI  - REPRODUCTIVE AND CHILD HEALTH SERVICES AND DEMOGRAPHIC CHANGE IN THE DISTRICTS OF
      UTTAR PRADESH, 2002-13.
AB  - This study examined the effect of reproductive and child health (RCH) services on
      fertility and child mortality in the districts of Uttar Pradesh. It specifically
      measured the effect of antenatal care, medical assistance at birth, child
      immunization and use of modern methods of contraception on Total Fertility Rate
      (TFR), Infant Mortality Rate (IMR) and Under-five Morality Rate (U5MR) before and
      after the National Rural Health Mission (NRHM) period. Data from the 2002-04
      District Level Household Survey (DLHS-2), 2012-13 Annual Health Survey (AHS) and
      the 2001 and 2011 Censuses of India were used. The TFR and U5MR were estimated
      from the Census of India with district as the unit of analysis. Descriptive
      statistics, composite indices, random- and fixed-effects models and difference-in
      difference models were used to understand the effect of RCH services on the
      reduction in TFR, IMR and the U5MR. The results suggest large inter-district
      variations in the coverage of RCH services in the state. During the post-NRHM
      period, improvement was highest in safe delivery followed by immunization
      coverage and antenatal care and least for contraceptive use in most districts.
      The relative ranking of districts has not changed much over time. In 2002-04, the
      RCH Index was highest in Lucknow (0.442) followed by Ballia and least in
      Kaushambi (0.115). By 2012-13, it was highest in Jhansi (0.741) and lowest in
      Shrawasti (0.241). The districts of Kaushambi, Unnao, Mahoba, Banda and Hardoi
      performed better in the RCH Index over time, while Ballia, Gautam Buddha Nagar,
      Kanpur Nagar, Pratapgarh and Sonbhadra remained poor. The RCH service coverage
      and demographic outcomes were poor in seven districts, particularly those in
      eastern and western Uttar Pradesh. The regression analyses suggest that the RCH
      Index exerts greater influence on the reduction in IMR and U5MR, while female
      literacy exerts greater influence on the reduction in TFR. The results of the
      hybrid model suggest that a 10% change in RCH Index would lead to a 3 point
      decline in IMR, and a 10% increase in female literacy would lead to a 0.2 point
      decline in TFR. The study suggests continuing investment in female education and
      RCH services with a greater focus on poor-performing districts to realize
      demographic and health targets.

PMID- 27692004
TI  - Inflammatory aspects of epileptogenesis: contribution of molecular inflammatory
      mechanisms.
AB  - OBJECTIVE: Epilepsy is a chronic neurological disease characterised with
      seizures. The aetiology of the most generalised epilepsies cannot be explicitly
      determined and the seizures are pronounced to be genetically determined by
      disturbances of receptors in central nervous system. Besides, neurotransmitter
      distributions or other metabolic problems are supposed to involve in
      epileptogenesis. Lack of adequate data about pharmacological agents that have
      antiepileptogenic effects point to need of research on this field. Thus, in this
      review, inflammatory aspects of epileptogenesis has been focussed via considering
      several concepts like role of immune system, blood-brain barrier and antibody
      involvement in epileptogenesis. METHODS: We conducted an evidence-based review of
      the literatures in order to evaluate the possible participation of inflammatory
      processes to epileptogenesis and also, promising agents which are effective to
      these processes. We searched PubMed database up to November 2015 with no date
      restrictions. RESULTS: In the present review, 163 appropriate articles were
      included. Obtained data suggests that inflammatory processes participate to
      epileptogenesis in several ways like affecting fibroblast growth factor-2 and
      tropomyosin receptor kinase B signalling pathways, detrimental proinflammatory
      pathways [such as the interleukin-1 beta (IL-1beta)-interleukin-1 receptor type 1
      (IL-1R1) system], mammalian target of rapamycin pathway, microglial activities,
      release of glial inflammatory proteins (such as macrophage inflammatory protein,
      interleukin 6, C-C motif ligand 2 and IL-1beta), adhesion molecules that are
      suggested to function in signalling pathways between neurons and microglia and
      also linkage between these molecules and proinflammatory cytokines. CONCLUSION:
      The literature research indicated that inflammation is a part of epileptogenesis.
      For this reason, further studies are necessary for assessing agents that will be
      effective in clinical use for therapeutic treatment of epileptogenesis.

PMID- 27692005
TI  - Impact of an Infection Control and Antimicrobial Stewardship Program on Solid
      Organ Transplantation and Hepatobiliary Surgical Site Infections.
AB  - OBJECTIVE The goal of this long-term quasi-experimental retrospective study was
      to assess the impact of a 5-year serial infection control and antimicrobial
      stewardship intervention on surgical site infections (SSIs). METHODS This study
      was conducted in a tertiary-care public teaching institution over a 5-year period
      from January 2010 to December 2014. All patients undergoing hepatobiliary surgery
      and liver, kidney, pancreas, and simultaneous pancreas-kidney transplantation
      were included. Outcomes were compared between a preintervention group (2010-2011)
      and a postintervention group (2012-2014). RESULTS A total of 1,424 procedures
      averaged an overall SSI rate of 11.2%. After implementation of the interventions,
      a decrease of 52.8% in SSI rates from 17.4% to 8.2% was observed (P50% (relative
      rate; P<.001) was observed in superficial incisional and organ-space infections
      between pre- and postintervention groups. In addition, a 54.9% decrease from
      19.7% to 8.9% (P<.001; OR, 2.2; 95% CI, 1.4-3.5) and a 51.6% decrease from 15.5%
      to 7.5% (P=.001; OR, 2.2; 95% CI, 1.4-3.5) were observed for SSI rates in
      hepatobiliary surgery and solid organ transplantation, respectively. The
      antimicrobial stewardship intervention increased overall conformity to the
      internal surgical prophylaxis protocol by 15.2% (absolute rate) from 45.1% to
      60.3% (P<.003; 95% CI, 5.4-24.9). CONCLUSIONS A long-term serial infection
      control and antimicrobial stewardship intervention decreased SSIs among patients
      undergoing hepatobiliary surgery and liver, kidney, pancreas, and simultaneous
      pancreas-kidney transplantation. Infect Control Hosp Epidemiol 2016;1468-1474.

PMID- 27692006
TI  - PERCEPTIONS OF STIGMA AND DISCRIMINATION IN HEALTH CARE SETTINGS TOWARDS SUB
      SAHARAN AFRICAN MIGRANT WOMEN LIVING WITH HIV/AIDS IN BELGIUM: A QUALITATIVE
      STUDY.
AB  - Stigma and discrimination within health care settings remain a public health
      challenge across diverse cultural environments and may have deleterious effects
      on mental and physical health. This study explores the causes, forms and
      consequences of HIV-related stigma and discrimination among migrant sub-Saharan
      African women living with HIV in Belgium. A qualitative study was conducted with
      44 HIV-positive sub-Saharan African migrant women between April 2013 and December
      2014 in health care settings in Belgium. Data were analysed using thematic
      content analysis. Twenty-five of the women reported overt stigma and
      discrimination and fifteen reported witnessing behaviours that they perceived to
      be stigmatizing and discriminatory in health care settings. The themes that
      emerged as to the causes of stigma and discrimination were: public perceptions of
      migrants and HIV, fear of contamination and institutional policies on HIV
      management. Reported forms of stigma and discrimination included: delayed or
      denied care, excessive precautions, blame and humiliation. The consequences of
      stigma and discrimination were: emotional stress, inconsistent health-care
      seeking behaviour and non-disclosure to non-HIV treating personnel. Stigma and
      discrimination in health care settings towards people with HIV, and more
      specifically towards HIV-positive sub-Saharan African migrant women, impedes
      sustainable preventive measures. Specialized education and training programmes
      for non-HIV health care providers require in-depth investigation.

PMID- 27692008
TI  - MATERNAL HEIGHT AND PRE-PREGNANCY WEIGHT STATUS ARE ASSOCIATED WITH FETAL GROWTH
      PATTERNS AND NEWBORN SIZE.
AB  - The impact of maternal height, pre-pregnancy weight status and gestational weight
      gain on fetal growth patterns and newborn size was analysed using a dataset of
      4261 singleton term births taking place at the Viennese Danube Hospital between
      2005 and 2013. Fetal growth patterns were reconstructed from three ultrasound
      examinations carried out at the 11th/12th, 20th/21th and 32th/33th weeks of
      gestation. Crown-rump length, biparietal diameter, fronto-occipital diameter,
      head circumference, abdominal transverse diameter, abdominal anterior-posterior
      diameter, abdominal circumference and femur length were determined. Birth weight,
      birth length and head circumference were measured immediately after birth. The
      vast majority of newborns were of normal weight, i.e. between 2500 and 4000 g.
      Maternal height showed a just-significant but weak positive association (r=0.03:
      p=0.039) with crown-rump length at the first trimester and with the majority of
      fetal parameters at the second trimester (r>0.06; p0.09; p0.08; p0.17; p0.13;
      p0.13; p<0.001), were significantly positively associated with newborn size. Some
      of these associations were quite weak and the statistical significance was mainly
      due to the large sample size. The association patterns between maternal height
      and pre-pregnancy weight status with fetal growth patterns (p<0.001), as well as
      newborn size (p<0.001), were independent of maternal age, nicotine consumption
      and fetal sex. In general, taller and heavier women gave birth to larger infants.
      This association between maternal size and fetal growth patterns was detectable
      from the first trimester onwards.

PMID- 27692007
TI  - Resilience to adversity and the early origins of disease.
AB  - For the past quarter century, scientists at the Center for Family Research at the
      University of Georgia have conducted research designed to promote understanding
      of normative developmental trajectories among low socioeconomic status African
      American children, youths, and young adults. In this paper, we describe a recent
      expansion of this research program using longitudinal, epidemiological studies
      and randomized prevention trials to test hypotheses about the origins of disease
      among rural African American youths. The contributions of economic hardship,
      downward mobility, neighborhood poverty, and racial discrimination to allostatic
      load and epigenetic aging are illustrated. The health benefits of supportive
      family relationships in protecting youths from these challenges are also
      illustrated. A cautionary set of studies is presented showing that some
      psychosocially resilient youths demonstrate high allostatic loads and accelerated
      epigenetic aging, suggesting that, for some, "resilience is just skin deep."
      Finally, we end on an optimistic note by demonstrating that family-centered
      prevention programs can have health benefits by reducing inflammation, helping to
      preserve telomere length, and inhibiting epigenetic aging.

PMID- 27692010
TI  - Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line
      rats to model treatment-resistant depression II: response to antidepressant
      augmentation strategies.
AB  - OBJECTIVE: Post-traumatic stress disorder (PTSD) displays high co-morbidity with
      major depression and treatment-resistant depression (TRD). Earlier work
      demonstrated exaggerated depressive-like symptoms in a gene*environment model of
      TRD and an abrogated response to imipramine. We extended the investigation by
      studying the behavioural and monoaminergic response to multiple antidepressants,
      viz. venlafaxine and ketamine with/without imipramine. METHODS: Male Flinders
      sensitive line (FSL) rats, a genetic model of depression, were exposed to a time
      dependent sensitisation (TDS) model of PTSD and compared with stress naive
      controls. 7 days after the TDS procedures, immobility and coping (swimming and
      climbing), behaviours in the forced swim test (FST) as well as hippocampal and
      cortical 5-hydroxyindoleacetic acid (5HIAA) and noradrenaline (NA) levels were
      analysed. Response to imipramine, venlafaxine and ketamine treatment (all 10
      mg/kg*7 days) alone and in combination were subsequently studied. RESULTS: TDS
      exacerbated depressive-like behaviour of FSL rats in the FST. Imipramine,
      venlafaxine and ketamine were ineffective as monotherapy in TDS-exposed FSL rats.
      However, combining imipramine with either venlafaxine or ketamine resulted in
      significant anti-immobility effects and enhanced coping behaviours. Only
      ketamine+imipramine (frontal-cortical 5HIAA and NA), ketamine alone (frontal
      cortical and hippocampal NA) and venlafaxine+imipramine (frontal-cortical NA)
      altered monoamine responses versus untreated TDS-exposed FSL rats. CONCLUSION:
      Exposure of FSL rats to TDS inhibits antidepressant response at behavioural and
      neurochemical levels. Congruent with TRD, imipramine plus venlafaxine or ketamine
      overcame treatment resistance in these animals. These data further support the
      hypothesis that exposure of FSL rats to a PTSD-like paradigm produces a valid
      animal model of TRD and warrants further investigation.

PMID- 27692009
TI  - Exploring genetic moderators and epigenetic mediators of contextual and family
      effects: From Gene * Environment to epigenetics.
AB  - In the current manuscript, we provide an overview of a research program at the
      University of Georgia's Center for Family Research designed to expand upon rapid
      and ongoing developments in the fields of genetics and epigenetics. By placing
      those developments in the context of translational research on family and
      community determinants of health and well-being among rural African Americans, we
      hope to identify novel, modifiable environments and biological processes. In the
      first section of the article, we review our earlier work on genotypic variation
      effects on the association between family context and mental and physical health
      outcomes as well as differential responses to family-based intervention. We then
      transition to discuss our more recent research on the association of family and
      community environments with epigenetic processes. In this second section of the
      article, we begin by briefly reviewing terminology and basic considerations
      before describing evidence that early environments may influence epigenetic
      motifs that potentially serve as mediators of long-term effects of early family
      and community environments on longer term health outcomes. We also provide
      evidence that genotype may sometimes influence epigenetic outcomes. Finally, we
      describe our recent efforts to use genome-wide characterization of epigenetic
      patterns to better understand the biological impact of protective parenting on
      long-term shifts in inflammatory processes and its potential implications for
      young adult health. As will be clear, research on epigenetics as a mediator of
      the connections between family/community processes and a range of health outcomes
      is still in its infancy, but the potential to develop important insights
      regarding mechanisms linking modifiable environments to biological processes and
      long-term health outcomes already is coming into view.

PMID- 27692011
TI  - Work-to-Family Enrichment and Conflict Profiles: Job Characteristics and
      Employees' Well-Being.
AB  - This article aims to analyze work-to-family conflict (WFC) and enrichment (WFE)
      profiles related to job characteristics and well-being at work and general well
      being. A cross-sectional survey data of 1885 employees was analyzed. The Latent
      Profile Analysis revealed that the five-profile solution exhibited strong
      statistical significance (p > .001). ANCOVAs were performed to analyze the
      relationship of the identified profiles with job characteristics and well-being.
      Employees in the Beneficial profile had the best perception of job
      characteristics (lowest demands and the highest control and support) and the
      highest well-being, and those in the Harmful profile had the lowest job
      characteristics perceptions and the lowest well-being. Through a comparison of
      the Moderate Active profile and the Moderate Harmful profile, WFE was found to
      buffer the effects of the WFC on well-being at work (burnout; engagement) and on
      general well-being (i.e., health perceptions). The promotion of WFE through
      higher job autonomy, job support, and fewer demands is a crucial aspect to
      consider. This study helps to consolidate the work-family balance typology and
      its effects on employees' well-being, and broadens this framework to consider job
      characteristics.

PMID- 27692012
TI  - How to support teenagers who are losing a parent to cancer: Bereaved young
      adults' advice to healthcare professionals-A nationwide survey.
AB  - OBJECTIVE: The loss of a parent to cancer is considered one of the most traumatic
      events a teenager can experience. Studies have shown that teenagers, from the
      time of diagnosis, are already extremely worried about the consequences of a
      parent's cancer but tend to be left to manage these concerns on their own. The
      present study aimed to explore young adults' advice to healthcare professionals
      on how to support teenagers who are losing a parent to cancer. METHODS: This work
      derives from a Swedish nationwide survey and employs a qualitative approach with
      a descriptive/interpretive design to obtain answers to an open-ended question
      concerning advice to healthcare professionals. Of the 851 eligible young adults
      who had lost a parent to cancer when they were 13-16 years of age within the
      previous 6 to 9 years, 622 participated in our survey (response rate = 73%). Of
      these 622 young adults, 481 responded to the open-ended question about what
      advice to give healthcare professionals. RESULTS: Four themes emerged: (1) to be
      seen and acknowledged; (2) to understand and prepare for illness, treatment, and
      the impending death; (3) to spend time with the ill parent, and (4) to receive
      support tailored to the individual teenager's needs. SIGNIFICANCE OF RESULTS:
      This nationwide study contributes hands-on suggestions to healthcare staff
      regarding attitudes, communication, and support from the perspective of young
      adults who, in their teenage years, lost a parent to cancer. Teenagers may feel
      better supported during a parent's illness if healthcare professionals take this
      manageable advice forward into practice and see each teenager as individuals;
      explain the disease, its treatments, and consequences; encourage teenagers to
      spend time with their ill parent; and recommend sources of support.

PMID- 27692013
TI  - A comparative study of patient characteristics, opinions, and outcomes, for
      patients who leave the emergency department before medical assessment.
AB  - OBJECTIVE: The emergency department (ED) left-without-being-seen (LWBS) rate is a
      performance indicator, although there is limited knowledge about why people
      leave, or whether they seek alternate care. We studied characteristics of ED LWBS
      patients to determine factors associated with LWBS. METHODS: We collected
      demographic data on LWBS patients at two urban hospitals. Sequential LWBS
      patients were contacted and surveyed using a standardized telephone survey. A
      matched group of patients who did not leave were also surveyed. Data were
      analysed using the Fisher exact test, chi-square test, and student t-test.
      RESULTS: The LWBS group (n=1508) and control group (n=1504) were matched for sex,
      triage category, recorded wait times, employment and education, and having a
      family physician. LWBS patients were younger, more likely to present in the
      evening or at night, and lived closer to the hospital. A long wait time was the
      most cited reason for leaving (79%); concern about medical condition was the most
      common reason for staying (96%). Top responses for improved likelihood of waiting
      were shorter wait times (LWBS, 66%; control, 31%) and more information on wait
      times (41%; 23%). A majority in both groups felt that their condition was a true
      emergency (63%; 72%). LWBS patients were more likely to seek further health care
      (63% v. 28%; p<0.001) and sooner (median time 1 day v. 2-4 days; p=0.002). Among
      patients who felt that their condition was not a true emergency, the top reason
      for ED attendance was the inability to see their family doctor (62% in both
      groups). CONCLUSION: LWBS patients had similar opinions, experiences, and
      expectations as control patients. The main reason for LWBS was waiting longer
      than expected. LWBS patients were more likely to seek further health care, and
      did so sooner. Patients wait because of concern about their health problem.
      Shorter wait times and improved communication may reduce the LWBS rate.

PMID- 27692014
TI  - Comparison of organoleptic quality and composition of beef from suckler bulls
      from different production systems.
AB  - Bull beef production is traditionally based on high concentrate rations fed
      indoors. Inclusion of grazed grass, which is generally a cheaper feed, would
      decrease the cost of bull beef production, but may affect beef quality.
      Accordingly, the organoleptic quality and composition of beef from continental
      sired suckler bulls (n=126) assigned to either ad libitum concentrates to
      slaughter (C), grass silage (GS) ad libitum for 120 days followed by C (GSC) or
      GS followed by 100 days at pasture and then C (GSPC) and slaughtered at target
      carcass weights (CW) of 360, 410 or 460 kg was examined. Tenderness, flavour
      liking and overall liking were lower (P<0.05) for GSPC than for C and GSC.
      Intramuscular fat content and soluble collagen proportion were lower (P<0.05) for
      GSPC than GSC which was lower (P<0.05) than C. Soluble collagen proportion was
      lower (P<0.05) for 460 kg than 410 kg CW, which was lower (P<0.05) than 360 kg
      CW. Inclusion of a grazing period decreased the ratings of tenderness, flavour
      liking and overall liking, but age of the bulls at slaughter had no clear
      influence on sensory characteristics.

PMID- 27692015
TI  - Simple dietary criteria to improve serum n-3 fatty acid levels of mothers and
      their infants.
AB  - OBJECTIVE: Sufficient maternal dietary intake of n-3 fatty acids (FA) supports
      offspring development. We aimed to construct simple criteria for dietary
      counselling to improve intake of n-3 FA. DESIGN: Serum phospholipid FA from
      mothers and infants were analysed by GC one month after delivery. Dietary intake
      of foods during pregnancy and one month after delivery were recorded using 3 d
      food diaries and an index for healthy eating was calculated. Fish consumption was
      established by questionnaires. Dietary consumption of foods resulting in an
      increase in serum n-3 FA was defined. SETTING: A mother-child follow-up study in
      Southwest Finland. SUBJECTS: Mothers (n 90) and 1-month-old infants (n 63).
      RESULTS: After delivery, the mother's consumption of fish at least three times
      per week resulted in an increase in total serum n-3 FA (mean difference (95 %
      CI): 1.7 (0.7, 2.8) % of total FA, P<0.001) and DHA (1.1 (0.5, 1.8) % of total
      FA, P<0.001) compared with non-consumers. Persistent fish intake once weekly
      throughout pregnancy increased total serum n-3 FA (P=0.001) and DHA (P<0.001).
      Overall, a healthy diet (middle and highest tertiles of healthy eating index
      score v. the lowest tertile) resulted in higher total serum n-3 FA (P=0.004) and
      DHA (P=0.008). Mother's diet along with higher serum levels of n-3 FA were
      related to serum FA levels in 1-month-old infants. CONCLUSIONS: An overall
      healthy diet and persistent consumption of fish at least once weekly throughout
      pregnancy or more frequent fish intake three times per week increases n-3 FA in
      serum phospholipids of both mothers and their infants.

PMID- 27692016
TI  - Obesity services planning framework for interprofessional primary care
      organizations.
AB  - : Aim We report on a formative project to develop an organization-level planning
      framework for obesity prevention and management services. BACKGROUND: It is
      common when developing new services to first develop a logic model outlining
      expected outcomes and key processes. This can be onerous for single primary care
      organizations, especially for complex conditions like obesity. METHODS: The
      initial draft was developed by the research team, based on results from provider
      and patient focus groups in one large Family Health Team (FHT) in Ontario. This
      draft was reviewed and activities prioritized by 20 FHTs using a moderated
      electronic consensus process. A national panel then reviewed the draft. Findings
      Providers identified five main target groups: pregnancy to 2, 3-12, 13-18, 18+
      years at health risk, and 18+ with complex care needs. Desired outcomes were
      identified and activities were prioritized under categories: raising awareness
      (eg, providing information and resources on weight-health), identification and
      initial management (eg, wellness care), follow-up management (eg, group
      programs), expanded services (eg, availability of team services), and practice
      initiatives (eg, interprofessional education). Overall, there was strong support
      for raising awareness by providing information on the weight-health connection
      and on community services. There was also strong support for growth assessment in
      pediatric care. In adults, there was strong support for wellness care/health
      check visits and episodic care to identify people for interventions, for group
      programs, and for additional provider education. CONCLUSIONS: Joint development
      by different teams proved useful for consensus on outcomes and for ensuring
      relevancy across practices. While priorities will vary depending on local
      context, the basic descriptions of care processes were endorsed by reviewers. Key
      next steps are to trial the use of the framework and for further implementation
      studies to find optimally effective approaches for obesity prevention and
      management across the lifespan.

PMID- 27692017
TI  - Internal Structure and Clinical Utility of the Anxiety Control Questionnaire
      Revised (ACQ-R) Spanish Version.
AB  - Perceived control has shown predictive value for anxiety severity symptoms as
      well as cognitive-behavior therapy outcomes. The most commonly used measure of
      perceived control is the Anxiety Control Questionnaire (ACQ), and more recently
      the ACQ Revised (ACQ-R). However, both questionnaires have shown structural
      inconsistencies among several studies. Also, although the ACQ and ACQ-R seem to
      be multidimensional instruments, a single total score have been commonly used.
      This study examined the internal structure of the ACQ-R Spanish version using
      exploratory factor and exploratory bi-factor analysis in a sample of 382 college
      students and 52 people diagnosed of panic disorder (with or without agoraphobia).
      Also, in this study we assessed the preliminary diagnostic value of the ACQ-R
      scores. The results indicated that the ACQ-R Spanish version structure consisted
      of two factors: one related with perceived control of internal emotional
      reactions (Emotion Control) and another related with perceived control of
      external events (Threat and Stress Control). Both specific factors can be
      adequately summarized by a general factor (General Anxiety Perception of Control;
      CFI = .973, TLI = .954, RMSEA = .039; p = .002), which accounted for 70% of the
      common explained variance. The correlations between the ACQ-R scores and with
      variables like anxiety (r = -.66) or anxiety sensitivity (r = -.50) presented the
      expected pattern of results. Either the two dimensions structure or the total
      score have proved to be a good tool to distinguish between participants with
      panic disorder and non-clinical samples (area under the curve = 0.79).

PMID- 27692018
TI  - The European School Fruit Scheme: impact on children's fruit and vegetable
      consumption in North Rhine-Westphalia, Germany.
AB  - OBJECTIVE: To assess the impact of the European School Fruit Scheme (SFS) in
      North Rhine-Westphalia, Germany, on children's fruit and vegetable (F&V)
      consumption, in particular frequency. DESIGN: The study consisted of a pre
      test/post-test design with an intervention (eight primary schools) and a control
      group (two primary schools). Children's F&V consumption frequency was measured
      prior to the introduction of the SFS in 2010 and after one year's delivery of F&V
      (2011). SETTING: Ten primary schools in North Rhine-Westphalia, Germany.
      SUBJECTS: In total, 499 primary-school children aged 6-11 years, 390 in the
      intervention and 109 in the control schools. RESULTS: Children highly appreciated
      the SFS. More than 90 % evaluated the programme positively. Children in the
      intervention group showed a significant increase in F&V intake frequency from
      baseline to follow-up, from on average 1.26 (sd 1.37) to 2.02 (sd 1.33) times/d
      (P=0.000). The intervention variable had a highly significant impact on
      children's F&V consumption frequency, even after controlling for gender, age and
      stay at school for lunch (beta=0.773; 95 % CI 0.59, 0.96). The SFS did not induce
      a reduction of F&V consumption at home. In the control group a non-significant
      decline in F&V consumption frequency from 1.31 (sd 1.26) to 1.18 (sd 1.34)
      times/d (P=0.325) was observed. CONCLUSION: One year after the programme's
      implementation, the SFS led to a significant short-term increase in children's
      F&V consumption.

PMID- 27692019
TI  - Practices, predictors and consequences of expressed breast-milk feeding in
      healthy full-term infants.
AB  - OBJECTIVE: To investigate the prevalence and predictors of expressed breast-milk
      feeding in healthy full-term infants and its association with total duration of
      breast-milk feeding. DESIGN: Prospective cohort study. SETTING: In-patient
      postnatal units of four public hospitals in Hong Kong. SUBJECTS: A total of 2450
      mother-infant pairs were recruited in 2006-2007 and 2011-2012 and followed up
      prospectively for 12 months or until breast-milk feeding had stopped. RESULTS:
      Across the first 6 months postpartum, the rate of exclusive expressed breast-milk
      feeding ranged from 5.1 to 8.0 % in 2006-2007 and from 18.0 to 19.8 % in 2011
      2012. Factors associated with higher rate of exclusive expressed breast-milk
      feeding included supplementation with infant formula, lack of previous breast
      milk feeding experience, having a planned caesarean section delivery and
      returning to work postpartum. Exclusive expressed breast-milk feeding was
      associated with an increased risk of early breast-milk feeding cessation when
      compared with direct feeding at the breast. The hazard ratio (95 % CI) ranged
      from 1.25 (1.04, 1.51) to 1.91 (1.34, 2.73) across the first 6 months.
      CONCLUSIONS: Mothers of healthy term infants should be encouraged and supported
      to feed directly at the breast. Exclusive expressed breast-milk feeding should be
      recommended only when medically necessary and not as a substitute for feeding
      directly at the breast. Further research is required to explore mothers' reasons
      for exclusive expressed breast-milk feeding and to identify the health outcomes
      associated with this practice.

PMID- 27692020
TI  - The Posttraumatic Growth Inventory: Factor Structure and Invariance in a Sample
      of Breast Cancer Patients and in a Non-Clinical Sample.
AB  - The Posttraumatic Growth Inventory (PTGI) is frequently used to assess positive
      changes following a traumatic event. The aim of the study is to examine the
      factor structure and the latent mean invariance of PTGI. A sample of 205 (M age =
      54.3, SD = 10.1) women diagnosed with breast cancer and 456 (M age = 34.9, SD =
      12.5) adults who had experienced a range of adverse life events were recruited to
      complete the PTGI and a socio-demographic questionnaire. We use Confirmatory
      Factor Analysis (CFA) to test the factor-structure and multi-sample CFA to
      examine the invariance of the PTGI between the two groups. The goodness of fit
      for the five-factor model is satisfactory for breast cancer sample (chi2(175) =
      396.265; CFI = .884; NIF = .813; RMSEA [90% CI] = .079 [.068, .089]), and good
      for non-clinical sample (chi2(172) = 574.329; CFI = .931; NIF = .905; RMSEA [90%
      CI] = .072 [.065, .078]). The results of multi-sample CFA show that the model fit
      indices of the unconstrained model are equal but the model that uses constrained
      factor loadings is not invariant across groups. The findings provide support for
      the original five-factor structure and for the multidimensional nature of
      posttraumatic growth (PTG). Regarding invariance between both samples, the factor
      structure of PTGI and other parameters (i.e., factor loadings, variances, and co
      variances) are not invariant across the sample of breast cancer patients and the
      non-clinical sample.

PMID- 27692021
TI  - Effects of Brief Behavioural Activation on Approach and Avoidance Tendencies in
      Acute Depression: Preliminary Findings.
AB  - BACKGROUND: It has been suggested that the behavioural activation (BA) treatments
      for depression unfold their effects, at least partly, through changes in approach
      and avoidance tendencies. However, as yet, little research has examined the
      cognitive effects of these interventions. AIMS: This study investigated the
      impact of a single session of BA on depressive symptomatology, self-reported
      avoidance, and behavioural approach and avoidance tendencies. METHOD: Forty-six
      patients with a diagnosis of Major Depression were recruited from primary care
      psychological therapies services and block randomized to either a single session
      of behavioural activation (n = 22) or waiting list control (n = 24) delivered by
      an unblinded therapist. Self-reports of symptoms and cognitive factors were
      assessed before and after the one-week intervention phase. Approach and avoidance
      behavioural tendencies were assessed using the Approach-Avoidance Task (AAT).
      RESULTS: Data from 40 participants (n = 20 in each group) was available for
      analyses. Depressive symptoms significantly decreased, and activation
      significantly increased from before to after treatment in the treatment group,
      but not in the control group. Performance on the AAT showed a trend indicating
      increased approach to positive valence stimuli in the treatment group, but not in
      the control group. Mediational analyses indicated small indirect effects of self
      reported change in activation as mediators of the effect of condition on
      symptoms. CONCLUSIONS: The findings suggest that a single session of BA can have
      significant effects on symptoms in clinically depressed patients. Results hint at
      the possibility that increased behavioural approach might mediate the effect of
      BA.

PMID- 27692022
TI  - Addition of granulosa cell mass to the culture medium of oocytes derived from
      early antral follicles increases oocyte growth, ATP content, and acetylation of
      H4K12.
AB  - The main aim of the present study was to examine the hypothesis that an increase
      in the number of granulosa cells surrounding developing bovine oocytes results in
      both high ATP levels and an increase in the acetylation level of H4K12 in oocytes
      grown in vitro. Oocyte-granulosa cell complexes (OGCs) were collected from early
      antral follicles (EAFs, 0.4-0.7 mm in diameter), and individually cultured on 96
      well plates with or without additional granulosa cell mass that had been prepared
      from other OGCs. After 16 days of culture, we examined: (i) the rate of antrum
      formation of the OGCs; (ii) the diameter, maturation, and fertilization rate of
      the oocytes; and (iii) the ATP content and acetylation level of H4K12 in the
      oocytes grown in vitro. Granulosa cell mass added to the culture medium
      contributed to the development of OGCs with a higher rate of antrum formation and
      oocyte growth. Furthermore, the addition of granulosa cells increased the ATP
      content and acetylation level of H4K12 in oocytes grown in vitro compared with
      those developed without addition of granulosa cells. In addition, there was a
      positive correlation between the ATP content in oocytes grown in vitro and the
      number of granulosa cells in the corresponding OGCs. The results suggest that
      granulosa cells play a role not only in the development of OGCs and the growth of
      oocytes, but also in the determination of ATP content and the acetylation of
      H4K12 in the oocytes developed in vitro.

PMID- 27692024
TI  - A home-based, carer-enhanced exercise program improves balance and falls efficacy
      in community-dwelling older people with dementia.
AB  - BACKGROUND: Older people with dementia are at increased risk of physical decline
      and falls. Balance and mood are significant predictors of falls in this
      population. The aim of this study was to determine the effect of a tailored home
      based exercise program in community-dwelling older people with dementia. METHODS:
      Forty-two participants with mild to moderate dementia were recruited from routine
      health services. All participants were offered a six-month home-based, carer
      enhanced, progressive, and individually tailored exercise program. Physical
      activity, quality of life, physical, and psychological assessments were
      administered at the beginning and end of the trial. RESULTS: Of 33 participants
      (78.6%) who completed the six-month reassessment ten (30%) reported falls and six
      (18%) multiple falls during the follow-up period. At reassessment, participants
      had better balance (sway on floor and foam), reduced concern about falls,
      increased planned physical activity, but worse knee extension strength and no
      change in depression scores. The average adherence to the prescribed exercise
      sessions was 45% and 22 participants (52%) were still exercising at trial
      completion. Those who adhered to >=70% of prescribed sessions had significantly
      better balance at reassessment compared with those who adhered to <70% of
      sessions. CONCLUSIONS: This trial of a tailored home-based exercise intervention
      presents preliminary evidence that this intervention can improve balance, concern
      about falls, and planned physical activity in community-dwelling older people
      with dementia. Future research should determine whether exercise interventions
      are effective in reducing falls and elucidate strategies for enhancing uptake and
      adherence in this population.

PMID- 27692023
TI  - Effects of initiating moderate wine intake on abdominal adipose tissue in adults
      with type 2 diabetes: a 2-year randomized controlled trial.
AB  - OBJECTIVE: To generate evidence-based conclusions about the effect of wine
      consumption on weight gain and abdominal fat accumulation and distribution in
      patients with type 2 diabetes. DESIGN: In the 2-year randomized controlled
      CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, patients following a
      Mediterranean diet were randomly assigned to drink 150 ml of mineral water, white
      wine or red wine with dinner for 2 years. Visceral adiposity and abdominal fat
      distribution were measured in a subgroup of sixty-five participants, using
      abdominal MRI. SETTING: Ben-Gurion University of the Negev, Soroka-Medical Center
      and the Nuclear Research Center Negev, Israel. SUBJECTS: Alcohol-abstaining
      adults with well-controlled type 2 diabetes. RESULTS: Forty-eight participants
      (red wine, n 27; mineral water, n 21) who completed a second MRI measurement were
      included in the 2-year analysis. Similar weight losses (sd) were observed: red
      wine 1.3 (3.9) kg; water 1.0 (4.2) kg (P=0.8 between groups). Changes (95 % CI)
      in abdominal adipose-tissue distribution were similar: red wine, visceral adipose
      tissue (VAT) -3.0 (-8.0, 2.0) %, deep subcutaneous adipose tissue (DSAT) +5.2 (
      1.1, 11.6) %, superficial subcutaneous adipose tissue (SSAT) -1.9 (-5.0, 1.2) %;
      water, VAT -3.2 (-8.9, 2.5) %, DSAT +2.9 (-2.8, 8.6) %, SSAT -0.15 (-3.3, 2.9) %.
      No changes in antidiabetic medication and no substantial changes in energy intake
      (+126 (sd 2889) kJ/d (+30.2 (sd 690) kcal/d), P=0.8) were recorded. A 2-year
      decrease in glycated Hb (beta=0.28, P=0.05) was associated with a decrease in
      VAT. CONCLUSIONS: Moderate wine consumption, as part of a Mediterranean diet, in
      persons with controlled diabetes did not promote weight gain or abdominal
      adiposity.

PMID- 27692025
TI  - Development and validation of the patient evaluation scale (PES) for primary
      health care in Nigeria.
AB  - BACKGROUND: Questionnaires developed for patient evaluation of the quality of
      primary care are often focussed on primary care systems in developed countries.
      Aim To report the development and validation of the patient evaluation scale
      (PES) designed for use in the Nigerian primary health care context. METHODS: An
      iterative process was used to develop and validate the questionnaire using
      patients attending 28 primary health centres across eight states in Nigeria. The
      development involved literature review, patient interviews, expert reviews,
      cognitive testing with patients and waves of quantitative cross-sectional
      surveys. The questionnaire's content validity, internal structures,
      acceptability, reliability and construct validity are reported. Findings The full
      and shortened version of PES with 27 and 18 items, respectively, were developed
      through these process. The low item non-response from the serial cross-sectional
      surveys depicts questionnaire's acceptability among the local population. PES
      short form (SF) has Cronbach's alpha of 0.87 and three domains (codenamed
      'facility', 'organisation' and 'health care') with Cronbach's alphas of 0.78,
      0.79 and 0.81, respectively. Items in the multi-dimensional questionnaire
      demonstrated adequate convergent and discriminant properties. PES-SF scores show
      significant positive correlation with scores of the full PES and also
      discriminated population groups in support of a priori hypotheses. CONCLUSION:
      The PES and PES-SF contain items that are relevant to the needs of patients in
      Nigeria. The good measurement properties of the questionnaire demonstrates its
      potential usefulness for patient-focussed quality improvement activities in
      Nigeria. There is still need to translate these questionnaires into major
      languages in Nigeria and assess their validity against external quality criteria.

PMID- 27692027
TI  - Principal Component Analysis of Working Memory Variables during Child and
      Adolescent Development.
AB  - Correlation and Principal Component Analysis (PCA) of behavioral measures from
      two experimental tasks (Delayed Match-to-Sample and Oddball), and standard scores
      from a neuropsychological test battery (Working Memory Test Battery for Children)
      was performed on data from participants between 6-18 years old. The correlation
      analysis (p 1), the scores of the first extracted component were significantly
      correlated (p < .05) to most behavioral measures, suggesting some commonalities
      of the processes of age-related changes in the measured variables. The results
      suggest that this first component would be related to age but also to individual
      differences during the cognitive maturation process across childhood and
      adolescence stages. The fourth component would represent the speed-accuracy trade
      off phenomenon as it presents loading components with different signs for
      reaction times and errors.

PMID- 27692026
TI  - Providers' perceptions of barriers and facilitators to disclosure of alcohol use
      by women veterans.
AB  - : Aim To better understand barriers and facilitators that hinder or help women
      veterans discuss their alcohol use with providers in primary care in order to
      better identify problematic drinking and enhance provider-patient communication
      about harmful drinking. BACKGROUND: Women presenting to primary care may be less
      likely than men to disclose potentially harmful alcohol use. No studies have
      qualitatively examined the perspectives of primary care providers about factors
      that affect accurate disclosure of alcohol use by women veterans during routine
      clinic visits. METHODS: Providers (n=14) were recruited from primary care at two
      veterans Administration Women's Health Clinics in California, United States. An
      open-ended interview guide was developed from domains of the consolidated
      framework for implementation science. Interviews elicited primary care providers'
      perspectives on barriers and facilitators to women veterans' (who may or may not
      be using alcohol in harmful ways) disclosure of alcohol use during routine clinic
      visits. Interview data were analyzed deductively using a combination of template
      analysis and matrix analysis. Findings Participants reported six barriers and
      five facilitators that they perceived affect women veteran's decision to
      accurately disclose alcohol use during screenings and openness to discussing
      harmful drinking with a primary care provider. The most commonly described
      barriers to disclosure were stigma, shame, and discomfort, and co-occuring mental
      health concerns, while building strong therapeutic relationships and using probes
      to 'dig deeper' were most often described as facilitators. Findings from this
      study may enhance provider-patient discussions about alcohol use and help primary
      care providers to better identify problematic drinking among women veterans,
      ultimately improving patient outcomes.

PMID- 27692028
TI  - An evaluation of the CARES(r) Dementia Basics Program among caregivers.
AB  - BACKGROUND: In 2014, the state of Oregon established Oregon Care Partners to
      provide high quality, free training to all dementia caregivers. This study
      evaluated participants' changes in knowledge, sense of competency in dementia
      caregiving, and ability to identify person-centered caregiving techniques after
      completing CARES(r) Dementia Basics online program, one of the educational
      resources available through this initiative. METHODS: A convenience sample of
      informal and formal caregivers (N = 51) provided data at three points in time;
      pre-test, post-test, and a follow-up test after an additional 30-day period to
      determine sustained changes in knowledge, sense of competency, and person
      centered care. RESULTS: From pre-test to post-test, modest improvements were
      detected in sense of competence in performing dementia care (ps < 0.01) and
      dementia-based knowledge, F(2, 150) = 7.71, p < 0.001, a multivariate effect size
      of w 2 = 0.09. Even though improvements in sense of competency were not
      universal, three out of five individual items demonstrated positive growth from
      pre-test to post-test as well as four out of the five items from pre-test to
      follow-up test. Importantly, gains observed in dementia-based knowledge from pre
      test to post-test were largely maintained at the 30-day follow-up. No significant
      changes were found in the correct identification of person-centered techniques
      after the training F(5, 150) = 1.63, p = 0.19. CONCLUSIONS: Future research
      should investigate how best to maintain educational interventions within the
      caregiving environment and to assess subsequent skill change.

PMID- 27692029
TI  - Development of Ca2+-release mechanisms during oocyte maturation of the starfish
      Asterina pectinifera.
AB  - An important step for successful fertilization and further development is the
      increase in intracellular Ca2+ in the activated oocyte. It has been known that
      starfish oocytes become increasingly sensitive to inositol 1,4,5-trisphosphate
      (IP3) during meiotic maturation to exhibit highly efficient IP3-induced Ca2+
      release (IICR) by the time of germinal vesicle breakdown (GVBD). However, we
      noted that the peak level of intracellular Ca2+ increase after insemination is
      already high in the maturing oocytes before GVBD. Using maturing oocytes before
      GVBD, we investigated Ca2+ release mechanisms other than IICR. We report here
      that Ca2+-release mechanisms dependent on nicotinic acid adenine dinucleotide
      phosphate (NAADP) and nicotinamide adenine dinucleotide (NADP), the precursor of
      NAADP, became functional prior to the development of IICR mechanisms. As with
      IP3, but unlike NAADP, the Ca2+ stores responsive to NADP are sensitized during
      the meiotic maturation induced by 1-methyladenine (1-MA). This suggests that the
      process may represent a physiological response to the maturation hormone. NADP
      dependent Ca2+ release in immature oocytes, however, did not induce oocyte
      maturation by itself, but was enhanced by the conditions mimicking the increases
      of intracellular Ca2+ and pH that take place in the maturing oocytes of starfish.

PMID- 27692030
TI  - Frailty and adverse outcomes: impact of multiple bed moves for older inpatients.
AB  - BACKGROUND: A consequence of pressure on hospitals to accommodate care needs of
      older patients is "boarding" or out-lying from their home ward. This may have
      greater adverse effects on older inpatients who are frail. METHODS: A
      retrospective matched cohort study was conducted in an outer metropolitan general
      hospital. Randomly selected patients hospitalized between July 2012 and June 2013
      under the care of an Older Person Evaluation Review and Assessment (OPERA) team
      (n = 300) were age and sex matched with patients under the care of general
      physicians (n = 300). Frequency of boarding and number of bed moves were recorded
      for all patients. For patients who had three or more moves, adverse outcomes were
      compared between the two groups. RESULTS: A higher proportion of OPERA patients
      (n = 143; 47.7%) were out-lied from medical wards compared with 94 (31.3%)
      General Medicine patients (p < 0.001). Three or more bed moves were recorded for
      67 (22.3%) OPERA and 24 (8%) General Medicine patients (p < 0.001). Of those with
      multiple moves, OPERA patients were more likely to have pre-morbid cognitive
      impairment (p = 0.005), to be moderately to severely frail (p = 0.016) and to
      suffer acute delirium and falls during admission (p = 0.03), compared with
      General Medicine patients. OPERA patients were also more at risk of adverse
      outcomes such as increased dependence, discharge to residential care or death (p
      = 0.023). CONCLUSION: Compared with age- and sex-matched General Medicine
      patients, OPERA patients were more likely to undergo multiple bed moves and out
      lying, which may have contributed to negative outcomes for these patients.

PMID- 27692031
TI  - Aggregation of cloned embryos in empty zona pellucida improves derivation
      efficiency of pig ES-like cells.
AB  - The development of embryonic stem cells (ESCs) from large animal species has
      become an important model for therapeutic cloning using ESCs derived by somatic
      cell nuclear transfer (SCNT). However, poor embryo quality and blastocyst
      formation have been major limitations for derivation of cloned ESCs (ntESCs). In
      this study, we have tried to overcome these problems by treating these cells with
      histone deacetylase inhibitors (HDACi) and aggregating porcine embryos. First,
      cloned embryos were treated with Scriptaid to confirm the effect of HDACi on
      cloned embryo quality. The Scriptaid-treated blastocysts showed significantly
      higher total cell numbers (29.50 +/- 2.10) than non-treated blastocysts (22.29 +/
      1.50, P < 0.05). Next, cloned embryo quality and blastocyst formation were
      analyzed in aggregates. Three zona-free, reconstructed, four-cell-stage SCNT
      embryos were injected into the empty zona of hatched parthenogenetic (PA)
      blastocysts. Blastocyst formation and total cell number of cloned blastocysts
      increased significantly for all aggregates (76.4% and 83.18 +/- 8.33) compared
      with non-aggregates (25.5% and 27.11 +/- 1.67, P < 0.05). Finally, aggregated
      blastocysts were cultured on a feeder layer to examine the efficiency of porcine
      ES-like cell derivation. Aggregated blastocysts showed a higher primary colony
      formation rate than non-aggregated cloned blastocysts (17.6 +/- 12.3% vs. 2.2 +/-
      1.35%, respectively, P < 0.05). In addition, derived ES-like cells showed typical
      characters of ESCs. In conclusion, the aggregation of porcine SCNT embryos at the
      four-cell stage could be a useful technique for improving the development rate
      and quality of porcine-cloned blastocysts and the derivation efficiency of
      porcine ntESCs.

PMID- 27692032
TI  - Acinetobacter pakistanensis Abbas et al. 2014 is a later heterotypic synonym of
      Acinetobacter bohemicus Krizova et al. 2014.
AB  - Two novel species names, Acinetobacter bohemicus and Acinetobacter pakistanensis,
      appeared on validation list no. 161 (January 2015) under priority numbers 26 and
      28, respectively. As the published data suggested a high similarity of the
      organisms associated with these names, we aimed to define their taxonomic
      relationship. The study set included all strains used in the original
      nomenclatural proposals, i.e. 25 strains of A. bohemicus and one strain of A.
      pakistanensis. The average nucleotide identity values (95.9 and 96.1 % based on
      blast and MUMmer, respectively) between the whole-genome sequences of A.
      bohemicus ANC 3994T and A. pakistanensis KCTC 42081T supported the identity of
      these type strains at the species level. Based on the genus-wide comparative
      analyses of the rpoB sequences and whole-cell fingerprints generated by matrix
      assisted laser desorption/ionization-time-of-flight MS, A. pakistanensis KCTC
      42081T fell within the respective clusters formed by the 25 A. bohemicus strains.
      The same picture was obtained on the basis of comparative analysis of 16S rRNA
      gene sequences of KCTC 42081T and three A. bohemicus strains. Finally, the
      metabolic and physiological features of KCTC 42081T were found to be congruent
      with those of A. bohemicus. Based on these results, we conclude that
      Acinetobacter pakistanensis is a later heterotypic synonym of Acinetobacter
      bohemicus.

PMID- 27692033
TI  - Huakuichenia soli gen. nov., sp. nov., a new member of the family
      Microbacteriaceae, isolated from contaminated soil.
AB  - A novel Gram-stain-positive, non-motile, rod-shaped bacterial strain designated
      LIP-1T was isolated from the contaminated soil of a pesticide factory in Xinyi,
      China, was investigated for its taxonomic allocation by a polyphasic approach.
      Cell growth occurred at 16-37  degrees C (optimum, 30  degrees C), in the
      presence of 0-2.0 % (w/v) NaCl (optimum, 0 %) and at pH 6.0-9.0 (optimum, pH
      7.0). The major fatty acids of strain LIP-1T were anteiso-C15 : 0 (50.8 %), iso
      C16 : 0 (17.6 %) and anteiso-C17 : 0 (17.4 %). The cell-wall peptidoglycan type
      was B2delta with 2,4-diaminobutyric acid as the diagnostic diamino acid. The
      major polar lipids were diphosphatidylglycerol and two unidentified glycolipids.
      The major menaquinones were MK-12 and MK-11. The genomic DNA G+C content was
      approximately 63.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences
      showed that strain LIP-1T formed a distinct clade within the radiation of the
      family Microbacteriaceae and had the highest sequence similarity with
      Microbacterium ginsengisoli Gsoil 259T (96.01 %) followed by Cryobacterium
      arcticum SK1T (94.94 %). On the basis of the phylogenetic analyses and distinct
      phenotypic characteristics, a new genus, namely Huakuichenia gen. nov., is
      proposed, harbouring the novel species Huakuichenia soli gen. nov., sp. nov. with
      the type strain LIP-1T (=CCTCC AB 2015422T=KCTC 39698T).

PMID- 27692034
TI  - Carboxylicivirga flava sp. nov., isolated from marine surface sediment.
AB  - A novel bacterial strain, designated Q15T, was isolated from sediments obtained
      from the Bohai Sea in China and subjected to a polyphasic taxonomic study. Cells
      of strain Q15T were Gram-stain-negative, strictly aerobic rods that produced
      circular, flat, orange colonies. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that Q15T was affiliated with the genus Carboxylicivirga in
      the family Marinilabiliaceae of the phylum Bacteroidetes. Strain Q15T differed
      genotypically from the type strains of the three recognized species of this genus
      (Carboxylicivirga taeanensis MEBiC 08903T, Carboxylicivirga mesophila MEBiC
      07026T and Carboxylicivirga linearis FB218T) and shared 94.0-95.2 % 16S rRNA gene
      sequence similarity with them. The DNA G+C content of strain Q15T was 44.7 mol%.
      The predominant cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0 and iso
      C17 : 0 3-OH, and menaquinone MK-7 was the main respiratory quinone. Polar lipids
      contained phosphatidylethanolamine, an unidentified aminolipid, an unidentified
      phospholipid and other unknown lipids. Based on the data from the current
      polyphasic analysis, a novel species, Carboxylicivirga flava sp. nov., is hereby
      proposed with Q15T (=CICC 23923T=KCTC 42707T) as the type strain.

PMID- 27692035
TI  - Acinetobactercelticus sp. nov., a psychrotolerant species widespread in natural
      soil and water ecosystems.
AB  - A novel, taxonomically unique group of six strains of the genus Acinetobacter was
      discovered during an exploratory study on strains culturable from soil and water
      natural ecosystems in the Bohemian part of the Czech Republic. Based on the
      comparative analyses of the 16S rRNA gene, gyrB and rpoB sequences, these strains
      formed strongly supported and internally coherent clusters (intracluster
      identities of >=99.9, >=96.1 and >=97.3 %, respectively), which were clearly
      separated from all known species of the genus Acinetobacter (<=98.7, <=83.2 and
      <=88.9 %, respectively). The distinctness of the group at the species level was
      evidenced also by the results of the genus-wide analyses of the whole-cell mass
      fingerprints of the six strains generated by matrix-assisted laser
      desorption/ionization-time-of-flight MS and the whole-genome sequence of a group
      member, ANC 4603T. Compared with the known species of the genus Acinetobacter,
      all six strains exhibited a unique phenotype, characterized by psychrotolerance
      (growth at 1  degrees C through 28  degrees C), the inability to grow at 32 
      degrees C and the ability to assimilate l-aspartate and malonate but not 2,3
      butanediol or citrate. Based on these results, the name Acinetobacter celticus
      sp. nov. is proposed for the taxon represented by the six strains. The type
      strain is ANC 4603T (=CCM 8700T=CCUG 69239T=CNCTC 7549T).

PMID- 27692036
TI  - Idiomarina tyrosinivorans sp. nov., isolated from estuarine surface water.
AB  - A tyrosine-metabolizing, Gram-stain-negative, strictly aerobic, non-spore
      forming, curved-rod-shaped, motile (due to monopolar flagellum) marine bacterium,
      designated strain CC-PW-9T, was isolated from estuarine water off Pingtung,
      Taiwan. Strain CC-PW-9T not only shared highest 16S rRNA gene sequence
      similarities with Idiomarina representatives (96.4-93.4 %, n=26), but also formed
      a distinct phyletic lineage and coherent phylogenetic cluster associated with
      those species. Cells of strain CC-PW-9T grew with 6-12 % (w/v) NaCl, at 20-40 
      degrees C and at pH 6-9. It produced predominant amounts of
      phosphatidylethanolamine, plus diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylserine, two unidentified phospholipids, an unidentified
      phosphoglycolipid, two unidentified lipids and an unidentified aminolipid in
      moderate to trace amounts. Fatty acids such as iso-C15 : 0, iso-C17 : 0 and iso
      C17 : 1omega9c and/or C16 : 010-methyl (summed feature 9) were found in major
      amounts. The DNA G+C content was 51.1 mol%. Ubiquinone-8 (Q-8) was the sole
      respiratory quinone. Based on evidence from this polyphasic taxonomic study,
      strain CC-PW-9T is considered to represent a novel species of the genus
      Idiomarina, affiliated to the family Idiomarinaceae, for which the name
      Idiomarina tyrosinivorans sp. nov. is proposed. The type strain is CC-PW-9T (=JCM
      19757T=BCRC 80745T).

PMID- 27692037
TI  - Gilvimarinus japonicus sp. nov., a cellulolytic and agarolytic marine bacterium
      isolated from coastal debris.
AB  - A cellulolytic and agarolytic bacterial strain, designated 12-2T, was isolated
      from a piece of cotton rope fragment washed ashore on a beach and was studied
      phenotypically, genotypically and phylogenetically. Analyses of 16S rRNA and gyrB
      gene sequences and DNA base composition suggested that the strain is a member of
      the genus Gilvimarinus. However, levels of 16S rRNA and gyrB gene sequence
      similarity between it and the type strains of Gilvimarinus species were no higher
      than 97.9 and 78.7 %, respectively, suggesting that the strain is distinct.
      Moreover, the results of DNA-DNA hybridization experiments and physiological
      characterization clearly differentiated the strain from its closest neighbours.
      The strain is therefore considered to represent a novel species of the genus
      Gilvimarinus, for which the name Gilvimarinus japonicus sp. nov. is proposed. The
      type strain is 12-2T (=NBRC 111987T=KCTC 52141T).

PMID- 27692038
TI  - Isolation and characterization of Acidobacterium ailaaui sp. nov., a novel member
      of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial
      mat.
AB  - A novel member of Acidobacteria was isolated from a microbial mat growing on a
      geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA).
      The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile
      and catalase and oxidase negative. Growth occurred aerobically from 15 to 55 
      degrees C (optimum, 40  degrees C) and at pH values from 4.5 to 7.0 (optimum,
      6.5). A limited range of sugars and organic acids supported growth. However,
      results of a genomic analysis suggested that various polysaccharides might be
      hydrolysed as carbon sources, and evidence for pectin degradation was observed in
      liquid cultures. A genomic analysis also revealed genes for a Group 1f uptake
      hydrogenase; assays with liquid cultures confirmed hydrogen consumption,
      including uptake at sub-atmospheric concentrations. Nitrate was not dissimilated
      to nitrite. Major membrane fatty acids included iso-C15 : 0 and iso-C17 : 0. The
      G+C content was 57.2mol%. A comparative genome analysis revealed an average
      nucleotide identity of 72.2 % between PMMR2T and its nearest cultured
      phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T);
      analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with
      Acidobacterium capsulatum ATCC 51196T. These results and other phenotypic
      differences indicated that strain PMMR2T represents a novel species in the genus
      Acidobacterium, for which the name Acidobacterium ailaaui sp. nov. is proposed.
      The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition
      to the genus Acidobacterium.

PMID- 27692040
TI  - Altererythrobacter sediminis sp. nov., isolated from lagoon sediments.
AB  - A Gram-stain-negative, non-motile, non-spore-forming, ovoid rod-shaped bacterium,
      designated strain CAU1172T, was isolated from lagoon sediments along the east
      coast of the Republic of Korea. Strain CAU1172T formed a yellow pigment on marine
      agar. Growth occurred at 20-37  degrees C (optimum, 30  degrees C), at pH 6.5-10
      (optimum, 7.5) and in the presence of 0-4 % (w/v) NaCl (optimum, 1 %).
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strain
      CAU1172T formed a separate lineage within the genus Altererythrobacter, and was
      most closely related to Altererythrobacter gangjinensis KJ7T (96.1 % similarity).
      Ubiquinone 10 (Q-10) was the predominant respiratory quinone. The dominant fatty
      acids were C18 : 1omega7c, C17 : 1omega6c and summed feature 3 (comprising C16 :
      1omega7c and/or C16 : 1omega6c). The polar lipids were composed of
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol,
      sphingoglycolipid, phospatidylcholine and four unidentified lipids. The DNA G+C
      content of strain CAU1172T was 63.2 mol%. On the basis of phenotypic and
      chemotaxonomic data, strain CAU1172T represents a novel species of the genus
      Altererythrobacter, for which the name Altererythrobacter sediminis sp. nov. is
      proposed. The type strain is CAU1172T (=KCTC 42453T=NBRC 110917T).

PMID- 27692039
TI  - Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within
      the Flaviviridae family.
AB  - Proposals are described for the assignment of recently reported viruses,
      infecting rodents, bats and other mammalian species, to new species within the
      Hepacivirus and Pegivirus genera (family Flaviviridae). Assignments into 14
      Hepacivirus species (Hepacivirus A-N) and 11 Pegivirus species (Pegivirus A-K)
      are based on phylogenetic relationships and sequence distances between conserved
      regions extracted from complete coding sequences for members of each proposed
      taxon. We propose that the species Hepatitis C virus is renamed Hepacivirus C in
      order to acknowledge its unique historical position and so as to minimize
      confusion. Despite the newly documented genetic diversity of hepaciviruses and
      pegiviruses, members of these genera remain phylogenetically distinct, and differ
      in hepatotropism and the possession of a basic core protein; pegiviruses in
      general lack these features. However, other characteristics that were originally
      used to support their division into separate genera are no longer definitive;
      there is overlap between the two genera in the type of internal ribosomal entry
      site and the presence of miR-122 sites in the 5' UTR, the predicted number of N
      linked glycosylation sites in the envelope E1 and E2 proteins, the presence of
      poly U tracts in the 3' UTR and the propensity of viruses to establish a
      persistent infection. While all classified hepaciviruses and pegiviruses have
      mammalian hosts, the recent description of a hepaci-/pegi-like virus from a shark
      and the likely existence of further homologues in other non-mammalian species
      indicate that further species or genera remain to be defined in the future.

PMID- 27692041
TI  - Functional analysis of a novel hydrogen peroxide resistance gene in Lactobacillus
      casei strain Shirota.
AB  - Lactic acid bacteria have a variety of mechanisms for tolerance to oxygen and
      reactive oxygen species, and these mechanisms differ among species. Lactobacillus
      casei strain Shirota grows well under aerobic conditions, indicating that the
      various systems involved in oxidative stress resistance function in this strain.
      To elucidate the mechanism of oxidative stress resistance in L. casei strain
      Shirota, we examined the transcriptome response to oxygen or hydrogen peroxide
      exposure. We then focused on an uncharacterized gene that was found to be up
      regulated by both oxygen and hydrogen peroxide stress; we named the gene hprA1
      (hydrogen peroxide resistance gene). This gene is widely distributed among
      lactobacilli. We investigated the involvement of this gene in oxidative stress
      resistance, as well as the mechanism of tolerance to hydrogen peroxide. Growth of
      L. casei MS105, an hprA1-disrupted mutant, was not affected by oxygen stress,
      whereas the survival rate of MS105 after hydrogen peroxide treatment was markedly
      reduced compared to that of the wild-type. However, the activity of MS105 in
      eliminating hydrogen peroxide was similar to that of the wild-type. We cloned
      hprA1 from L. caseiShirota and purified recombinant HprA1 protein from
      Escherichia coli. We demonstrated that the recombinant HprA1 protein bound to
      iron and prevented the formation of a hydroxyl radical in vitro. Thus, HprA1
      protein probably contributes to hydrogen peroxide tolerance in L. casei strain
      Shirota by binding to iron in the cells and preventing the formation of a
      hydroxyl radical.

PMID- 27692042
TI  - Characterization of germinants and their receptors for spores of non-food-borne
      Clostridium perfringens strain F4969.
AB  - Clostridium perfringens type A can cause both food poisoning (FP) and non-food
      borne (NFB) gastrointestinal diseases. Our previous study reported that a mixture
      of l-asparagine and KCl (AK)-germinated spores of FP and NFB isolates well, but
      KCl and, to a lesser extent, l-asparagine induced spore germination only in FP
      isolates. We now report that the germination response of FP and NFB spores
      differsignificantly in several defined germinants and rich media. Spores of NFB
      strain F4969 gerAA, gerKA-KC or gerKC mutants lacking specific germinant receptor
      proteins germinated more slowly than wild-type spores with rich media, did not
      germinate with AK and germinated poorly compared to wild-type spores with l
      cysteine. The germination defects in the gerKA-KC spores were largely due to loss
      of GerKC as (i) gerKA spores germinated significantly with all tested germinants,
      while gerKC spores exhibited poor or no germination; and (ii) germination defects
      in gerKC spores were largely restored by expressing the wild-type gerKA-KC operon
      in trans. We also found that gerKA-KC, gerAA and gerKC spores, but not gerKA
      spores, released dipicolinic acid at a slower rate than wild-type spores with AK.
      The colony-forming efficiency of F4969 gerKC spores was also ~35-fold lower than
      that of wild-type spores, while gerAA and wild-type spores had similar viability.
      Collectively, these results suggest that the GerAA and GerKC proteins play roles
      in normal germination of C. perfringens NFB isolates and that GerKC, but not
      GerAA, is important in these spores' apparent viability.

PMID- 27692043
TI  - Wolbachia restricts insect-specific flavivirus infection in Aedes aegypti cells.
AB  - Mosquito-borne viruses are known to cause disease in humans and livestock and are
      often difficult to control due to the lack of specific antivirals and vaccines.
      The Wolbachia endosymbiont has been widely studied for its ability to restrict
      positive-strand RNA virus infection in mosquitoes, although little is known about
      the precise antiviral mechanism. In recent years, a variety of insect-specific
      viruses have been discovered in mosquitoes and an interaction with mosquito-borne
      viruses has been reported for some of them; however, nothing is known about the
      effect of Wolbachia on insect-specific virus infection in mosquitoes. Here, we
      show that transinfection of the Drosophila-derived wMelPop Wolbachia strain into
      Aedes aegypti-derived cells resulted in inhibition and even clearance of the
      persistent cell-fusing agent flavivirus infection in these cells. This broadens
      the antiviral activity of Wolbachia from acute infections to persistent
      infections and from arboviruses to mosquito-specific viruses. In contrast, no
      effect on the Phasi Charoen-like bunyavirus persistent infection in these cells
      was observed, suggesting a difference in Wolbachia inhibition between positive-
      and negative-strand RNA viruses.

PMID- 27692044
TI  - Molecular epidemiology and the evolution of human coxsackievirus A6.
AB  - Coxsackievirus A6 (CV-A6) is a major aetiologic agent for hand, foot and mouth
      disease (HFMD) in recent years. HFMD outbreaks associated with CV-A6 resulted
      from the evolutionary dynamics of CV-A6 and the appearance of novel recombinant
      forms (RFs). To examine this, 151 variants collected in 2013 and 2014 from
      Germany, Spain, Sweden, Denmark and Thailand were genotyped for the VP1 capsid
      and 3Dpol genes. Analysis of the VP1 gene showed an increasing correspondence
      between CV-A6 genome recombination and sequence divergence (estimated
      substitution rate of 8.1*10-3 substitutions site-1 year-1 and RF half-life of 3.1
      years). Bayesian phylogenetic analysis showed that recent recombination groups
      (RF-E, -F, -H, -J and -K) shared a common ancestor (RF-A). Thirty-nine full
      length genomes of different RFs revealed recombination breakpoints between the 2A
      2C and the 5' UTRs. The emergence of new CV-A6 recombination groups has become
      widespread in Europe and Asia within the last 8 years.

PMID- 27692045
TI  - Herpes simplex virus particles interact with chemokines and enhance cell
      migration.
AB  - Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively) are among
      the most prevalent human pathogens, causing a variety of diseases. HSV modulation
      of the chemokine network remains poorly understood. We have previously identified
      secreted glycoprotein G (SgG) as the first viral chemokine-binding protein that
      enhances chemokine function as a novel viral immunomodulatory mechanism. However,
      gG is also present at the viral envelope and its role in the virus particle
      remains unknown. Here we have addressed the chemokine-binding capacity of HSV
      particles and the functionality of such interaction in vitro. We adapted surface
      plasmon resonance assays and demonstrated the ability of HSV particles to bind a
      specific set of human chemokines with high affinity. Moreover, we identified gG
      as the envelope glycoprotein mediating such interaction, as shown by the lack of
      binding to a HSV-1 gG mutant. In contrast to HSV-1, HSV-2 gG is cleaved and the
      chemokine-binding domain is secreted (SgG2). However, we found that HSV-2
      particles retain the ability to bind chemokines, potentially through SgG2
      associated to the viral envelope or non-processed precursor protein. Moreover, we
      found that HSV particles increase cell migration independently of chemokine
      binding to envelope gG. This work provides insights into HSV manipulation of the
      host immune system.

PMID- 27692046
TI  - Transfer of the potato plant isolates of Pectobacterium wasabiae to
      Pectobacterium parmentieri sp. nov.
AB  - Pectobacterium wasabiae was originally isolated from Japanese horseradish
      (Eutrema wasabi), but recently some Pectobacterium isolates collected from potato
      plants and tubers displaying blackleg and soft rot symptoms were also assigned to
      P. wasabiae. Here, combining genomic and phenotypical data, we re-evaluated their
      taxonomic position. PacBio and Illumina technologies were used to complete the
      genome sequences of P. wasabiae CFBP 3304T and RNS 08-42-1A. Multi-locus sequence
      analysis showed that the P. wasabiae strains RNS 08-42-1A, SCC3193, CFIA1002 and
      WPP163, which were collected from potato plant environment, constituted a
      separate clade from the original Japanese horseradish P. wasabiae. The taxonomic
      position of these strains was also supported by calculation of the in-silico DNA
      DNA hybridization, genome average nucleotide indentity, alignment fraction and
      average nucleotide indentity values. In addition, they were phenotypically
      distinguished from P. wasabiae strains by producing acids from (+)-raffinose,
      alpha-d(+)-alpha-lactose, d(+)-galactose and (+)-melibiose but not from methyl
      alpha-d-glycopyranoside, (+)-maltose or malonic acid. The name Pectobacterium
      parmentieri sp. nov. is proposed for this taxon; the type strain is RNS 08-42-1AT
      (=CFBP 8475T=LMG 29774T).

PMID- 27692047
TI  - Discovery of a polyomavirus in European badgers (Meles meles) and the evolution
      of host range in the family Polyomaviridae.
AB  - Polyomaviruses infect a diverse range of mammalian and avian hosts, and are
      associated with a variety of symptoms. However, it is unknown whether the viruses
      are found in all mammalian families and the evolutionary history of the
      polyomaviruses is still unclear. Here, we report the discovery of a novel
      polyomavirus in the European badger (Meles meles), which to our knowledge
      represents the first polyomavirus to be characterized in the family Mustelidae,
      and within a European carnivoran. Although the virus was discovered
      serendipitously in the supernatant of a cell culture inoculated with badger
      material, we subsequently confirmed its presence in wild badgers. The European
      badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1).
      The genome is 5187 bp long and encodes proteins typical of polyomaviruses.
      Phylogenetic analyses including all known polyomavirus genomes consistently group
      MmelPyV1 with California sea lion polyomavirus 1 across all regions of the
      genome. Further evolutionary analyses revealed phylogenetic discordance amongst
      polyomavirus genome regions, possibly arising from evolutionary rate
      heterogeneity, and a complex association between polyomavirus phylogeny and host
      taxonomic groups.

PMID- 27692048
TI  - Infectivity of wild bird-origin avian paramyxovirus serotype 1 and vaccine
      effectiveness in chickens.
AB  - Newcastle disease virus, a prototype avian paramyxovirus serotype 1 (APMV-1),
      causes economically devastating disease in avian species around the world.
      Newcastle disease is enzootic in Pakistan and recurrent outbreaks are frequent in
      multiple avian species even after continuous and extensive use of vaccines. A
      number of APMV-1 and pigeon paramyxovirus serotype 1 (PPMV-1) strains have been
      isolated and genetically characterized in recent years. However, the impact of
      recently characterized wild bird-origin APMVs in domestic poultry, and the
      potency of routinely used vaccines against these novel and genetically diverse
      viruses remain unknown. Here, we applied next-generation sequencing for unbiased
      complete genome characterization of APMV-1 and PPMV-1 strains isolated from
      clinically diseased peacocks (Pavocristatus) and pigeons (Columbalivia),
      respectively. Global phylodynamics and evolutionary analysis demonstrates
      Pigeon/MZS-UVAS-Pak/2014 is clustered into lineage 4 (or genotype VI) and
      Peacock/MZS-UVAS-Pak/2014 into lineage 5 (or genotype VII). The genomes of both
      isolates encoded for polybasic residues (112RRQKR?F117) at the fusion protein
      cleavage motif along with a number of important substitutions in the surface
      glycoproteins compared with the vaccine strains. Clinicopathological and
      immunological investigations in domesticated chickens indicate that these
      isolates can potentially transmit between tested avian species, can cause
      systemic infections, and can induce antibodies that are unable to prevent virus
      shedding. Collectively, the data from these genomic and biological assessments
      highlight the potential of wild birds in transmitting APMVs to domesticated
      chickens. The study also demonstrates that the current vaccine regimens are
      incapable of providing complete protection against wild bird-origin APMVs and
      PPMVs.

PMID- 27692061
TI  - Effects of freezing and activation on membrane quality and DNA damage in Xenopus
      tropicalis and Xenopus laevis spermatozoa.
AB  - There is growing concern over the effect of sperm cryopreservation on DNA
      integrity and the subsequent development of offspring generated from this
      cryopreserved material. In the present study, membrane integrity and DNA
      stability of Xenopus laevis and Xenopus tropicalis spermatozoa were evaluated in
      response to cryopreservation with or without activation, a process that happens
      upon exposure to water to spermatozoa of some aquatic species. A dye exclusion
      assay revealed that sperm plasma membrane integrity in both species decreased
      after freezing, more so for X. laevis than X. tropicalis spermatozoa. The sperm
      chromatin dispersion (SCD) test showed that for both X. tropicalis and X. laevis,
      activated frozen spermatozoa produced the highest levels of DNA fragmentation
      compared with all fresh samples and frozen non-activated samples (P<0.05).
      Understanding the nature of DNA and membrane damage that occurs in cryopreserved
      spermatozoa from Xenopus species represents the first step in exploiting these
      powerful model organisms to understand the developmental consequences of
      fertilising with cryopreservation-damaged spermatozoa.

PMID- 27692062
TI  - Assessing change in perceived community leadership readiness in the Obesity
      Prevention and Lifestyle program.
AB  - Issue addressed The context of community-based childhood obesity prevention
      programs can influence the effects of these intervention programs. Leadership
      readiness for community mobilisation for childhood obesity prevention is one such
      contextual factor. This study assessed perceived community leadership readiness
      (PCLR) at two time points in a state-wide, multisite community-based childhood
      obesity prevention program. Methods PCLR was assessed across 168 suburbs of 20
      intervention communities participating in South Australia's Obesity Prevention
      and Lifestyle (OPAL) program. Using a validated online PCLR tool, four key
      respondents from each community rated each suburb within their respective
      community on a nine-point scale for baseline and 2015. Average PCLR and change
      scores were calculated using the general linear model with suburbs nested in
      communities. Relationships between demographic variables and change in PCLR were
      evaluated using multiple regression. Ease of survey use was also assessed.
      Results Average PCLR increased between baseline (3.51, s.d.=0.82) and 2015 (5.23,
      s.d.=0.89). PCLR rose in 18 of 20 intervention communities. PCLR was inversely
      associated with suburb population size (r2=0.03, P=0.03, beta=-0.25) and
      positively associated with intervention duration (r2 change=0.08, P=0.00,
      beta=0.29). Only 8% of survey respondents considered the online assessment tool
      difficult to use. Conclusions PCLR increased over the course of the OPAL
      intervention. PCLR varied between and within communities. Online assessment of
      PCLR has utility for multisite program evaluations. So what? Use of a novel,
      resource-efficient online tool to measure the key contextual factors of PCLR has
      enabled a better understanding of the success and generalisability of the OPAL
      program.

PMID- 27692064
TI  - Phenotypic plasticity as an adaptation to a functional trade-off.
AB  - We report the evolution of a phenotypically plastic behavior that circumvents the
      hardwired trade-off that exists when resources are partitioned between growth and
      motility in Escherichia coli. We propagated cultures in a cyclical environment,
      alternating between growth up to carrying capacity and selection for chemotaxis.
      Initial adaptations boosted overall swimming speed at the expense of growth. The
      effect of the trade-off was subsequently eased through a change in behavior;
      while individual cells reduced motility during exponential growth, the faction of
      the population that was motile increased as the carrying capacity was approached.
      This plastic behavior was produced by a single amino acid replacement in FliA, a
      regulatory protein central to the chemotaxis network. Our results illustrate how
      phenotypic plasticity potentiates evolvability by opening up new regions of the
      adaptive landscape.

PMID- 27692065
TI  - Sparse activity of identified dentate granule cells during spatial exploration.
AB  - In the dentate gyrus - a key component of spatial memory circuits - granule cells
      (GCs) are known to be morphologically diverse and to display heterogeneous
      activity profiles during behavior. To resolve structure-function relationships,
      we juxtacellularly recorded and labeled single GCs in freely moving rats. We
      found that the vast majority of neurons were silent during exploration. Most
      active GCs displayed a characteristic spike waveform, fired at low rates and
      showed spatial activity. Primary dendritic parameters were sufficient for
      classifying neurons as active or silent with high accuracy. Our data thus support
      a sparse coding scheme in the dentate gyrus and provide a possible link between
      structural and functional heterogeneity among the GC population.

PMID- 27692063
TI  - ATPase activity of the DEAD-box protein Dhh1 controls processing body formation.
AB  - Translational repression and mRNA degradation are critical mechanisms of
      posttranscriptional gene regulation that help cells respond to internal and
      external cues. In response to certain stress conditions, many mRNA decay factors
      are enriched in processing bodies (PBs), cellular structures involved in
      degradation and/or storage of mRNAs. Yet, how cells regulate assembly and
      disassembly of PBs remains poorly understood. Here, we show that in budding
      yeast, mutations in the DEAD-box ATPase Dhh1 that prevent ATP hydrolysis, or that
      affect the interaction between Dhh1 and Not1, the central scaffold of the CCR4
      NOT complex and an activator of the Dhh1 ATPase, prevent PB disassembly in vivo.
      Intriguingly, this process can be recapitulated in vitro, since recombinant Dhh1
      and RNA, in the presence of ATP, phase-separate into liquid droplets that rapidly
      dissolve upon addition of Not1. Our results identify the ATPase activity of Dhh1
      as a critical regulator of PB formation.

PMID- 27692067
TI  - Social observation enhances cross-environment activation of hippocampal place
      cell patterns.
AB  - Humans and animals frequently learn through observing or interacting with others.
      The local enhancement theory proposes that presence of social subjects in an
      environment facilitates other subjects' understanding of the environment. To
      explore the neural basis of this theory, we examined hippocampal place cells,
      which represent spatial information, in rats as they stayed in a small box while
      a demonstrator rat running on a separate, nearby linear track, and as they ran on
      the same track themselves. We found that place cell firing sequences during self
      running on the track also appeared in the box. This cross-environment activation
      occurred even prior to any self-running experience on the track and was absent
      without a demonstrator. Our data thus suggest that social observation can
      facilitate the observer's spatial representation of an environment without actual
      self-exploration. This finding may contribute to neural mechanisms of local
      enhancement.

PMID- 27692066
TI  - Macrophage PPARgamma inhibits Gpr132 to mediate the anti-tumor effects of
      rosiglitazone.
AB  - Tumor-associated macrophage (TAM) significantly contributes to cancer
      progression. Human cancer is enhanced by PPARgamma loss-of-function mutations,
      but inhibited by PPARgamma agonists such as TZD diabetes drugs including
      rosiglitazone. However, it remains enigmatic whether and how macrophage
      contributes to PPARgamma tumor-suppressive functions. Here we report that
      macrophage PPARgamma deletion in mice not only exacerbates mammary tumor
      development but also impairs the anti-tumor effects of rosiglitazone.
      Mechanistically, we identify Gpr132 as a novel direct PPARgamma target in
      macrophage whose expression is enhanced by PPARgamma loss but repressed by
      PPARgamma activation. Functionally, macrophage Gpr132 is pro-inflammatory and pro
      tumor. Genetic Gpr132 deletion not only retards inflammation and cancer growth
      but also abrogates the anti-tumor effects of PPARgamma and rosiglitazone.
      Pharmacological Gpr132 inhibition significantly impedes mammary tumor malignancy.
      These findings uncover macrophage PPARgamma and Gpr132 as critical TAM
      modulators, new cancer therapeutic targets, and essential mediators of TZD anti
      cancer effects.

PMID- 27692068
TI  - The novel SH3 domain protein Dlish/CG10933 mediates fat signaling in Drosophila
      by binding and regulating Dachs.
AB  - Much of the Hippo and planar cell polarity (PCP) signaling mediated by the
      Drosophila protocadherin Fat depends on its ability to change the subcellular
      localization, levels and activity of the unconventional myosin Dachs. To better
      understand this process, we have performed a structure-function analysis of
      Dachs, and used this to identify a novel and important mediator of Fat and Dachs
      activities, a Dachs-binding SH3 protein we have named Dlish. We found that Dlish
      is regulated by Fat and Dachs, that Dlish also binds Fat and the Dachs regulator
      Approximated, and that Dlish is required for Dachs localization, levels and
      activity in both wild type and fat mutant tissue. Our evidence supports dual
      roles for Dlish. Dlish tethers Dachs to the subapical cell cortex, an effect
      partly mediated by the palmitoyltransferase Approximated under the control of
      Fat. Conversely, Dlish promotes the Fat-mediated degradation of Dachs.

PMID- 27692069
TI  - The fail-safe mechanism of post-transcriptional silencing of unspliced HAC1 mRNA.
AB  - HAC1 encodes a transcription factor that is the central effector of the unfolded
      protein response (UPR) in budding yeast. When the UPR is inactive, HAC1 mRNA is
      stored as an unspliced isoform in the cytoplasm and no Hac1 protein is
      detectable. Intron removal is both necessary and sufficient to relieve the post
      transcriptional silencing of HAC1 mRNA, yet the precise mechanism by which the
      intron prevents Hac1 protein accumulation has remained elusive. Here, we show
      that a combination of inhibited translation initiation and accelerated protein
      degradation-both dependent on the intron-prevents the accumulation of Hac1
      protein when the UPR is inactive. Functionally, both components of this fail-safe
      silencing mechanism are required to prevent ectopic production of Hac1 protein
      and concomitant activation of the UPR. Our results provide a mechanistic
      understanding of HAC1 regulation and reveal a novel strategy for complete post
      transcriptional silencing of a cytoplasmic mRNA.

PMID- 27692073
TI  - The Orwellian Nature of Radio-Frequency Identification in the Perioperative
      Setting.

PMID- 27692072
TI  - The Power of Respect.

PMID- 27692070
TI  - Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment
      by genome cyclization.
AB  - Viral replicase recruitment and long-range RNA interactions are essential for RNA
      virus replication, yet the mechanism of their interplay remains elusive.
      Flaviviruses include numerous important human pathogens, e.g., dengue virus
      (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, conformation
      tunable cis-acting element named 5'-UAR-flanking stem (UFS) in the flavivirus
      genomic 5' terminus. We demonstrated that the UFS was critical for efficient NS5
      recruitment and viral RNA synthesis in different flaviviruses. Interestingly,
      stabilization of the DENV UFS impaired both genome cyclization and vRNA
      replication. Moreover, the UFS unwound in response to genome cyclization, leading
      to the decreased affinity of NS5 for the viral 5' end. Thus, we propose that the
      UFS is switched by genome cyclization to regulate dynamic RdRp binding for vRNA
      replication. This study demonstrates that the UFS enables communication between
      flavivirus genome cyclization and RdRp recruitment, highlighting the presence of
      switch-like mechanisms among RNA viruses.

PMID- 27692074
TI  - Analyzing Quality Assessment and Performance Improvement Programs in Ambulatory
      Surgery Centers.

PMID- 27692075
TI  - Big Data and Perioperative Nursing.
AB  - Big data are large volumes of digital data that can be collected from disparate
      sources and are challenging to analyze. These data are often described with the
      five "Vs": volume, velocity, variety, veracity, and value. Perioperative nurses
      contribute to big data through documentation in the electronic health record
      during routine surgical care, and these data have implications for clinical
      decision making, administrative decisions, quality improvement, and big data
      science. This article explores methods to improve the quality of perioperative
      nursing data and provides examples of how these data can be combined with broader
      nursing data for quality improvement. We also discuss a national action plan for
      nursing knowledge and big data science and how perioperative nurses can engage in
      collaborative actions to transform health care. Standardized perioperative
      nursing data has the potential to affect care far beyond the original patient.

PMID- 27692076
TI  - Totally Endoscopic Robotic Mitral Valve Surgery.
AB  - Mitral valve dysfunction can seriously impair patients' lives and may require
      valve repair or replacement. Surgery can be performed using techniques including
      sternotomy; right thoracotomy with or without robot assistance; and the totally
      endoscopic robotic technique, which requires percutaneous techniques, femoral
      cannulation, and endovascular aortic cross-clamping. The totally endoscopic
      robotic technique has been facilitated by minimally invasive surgical techniques,
      the evolution of endoscopic techniques, and the development of surgical robots.
      These advances have enhanced the view of the surgical field and provide better
      exposure for the repair or replacement of the mitral valve and subvalvular
      apparatus. This article describes the totally endoscopic robotic approach to
      mitral valve surgery as performed at Temple University Hospital, Philadelphia,
      Pennsylvania.

PMID- 27692071
TI  - Evidence for evolutionary divergence of activity-dependent gene expression in
      developing neurons.
AB  - Evolutionary differences in gene regulation between humans and lower mammalian
      experimental systems are incompletely understood, a potential translational
      obstacle that is challenging to surmount in neurons, where primary tissue
      availability is poor. Rodent-based studies show that activity-dependent
      transcriptional programs mediate myriad functions in neuronal development, but
      the extent of their conservation in human neurons is unknown. We compared
      activity-dependent transcriptional responses in developing human stem cell
      derived cortical neurons with those induced in developing primary- or stem cell
      derived mouse cortical neurons. While activity-dependent gene-responsiveness
      showed little dependence on developmental stage or origin (primary tissue vs.
      stem cell), notable species-dependent differences were observed. Moreover,
      differential species-specific gene ortholog regulation was recapitulated in
      aneuploid mouse neurons carrying human chromosome-21, implicating
      promoter/enhancer sequence divergence as a factor, including human-specific
      activity-responsive AP-1 sites. These findings support the use of human neuronal
      systems for probing transcriptional responses to physiological stimuli or indeed
      pharmaceutical agents.

PMID- 27692077
TI  - Perioperative Heat Loss Prevention-A Feasibility Trial.
AB  - Preventing unplanned perioperative hypothermia is crucial. Thermal reflective
      blankets may reduce heat loss, promote normothermia, increase patient comfort,
      and decrease cotton blanket expenses. Our purpose was to determine whether a
      thermal reflective blanket plus one warmed cotton blanket provides better
      temperature control and thermal comfort than warmed cotton blankets only. We
      compared two groups of perioperative patients who received a thermal reflective
      blanket plus one warmed cotton blanket (n = 110) or warmed cotton blankets only
      (n = 114) for temperature control and comfort, and we evaluated outcomes in the
      preoperative holding area, the OR, and the postanesthesia care unit. There were
      no significant differences in patient temperature or comfort between groups. Use
      of thermal reflective blankets led to significantly reduced use of warmed cotton
      blankets (t209 = -10.51, P < .001), and a cost threshold for clinical adoption
      was identified. The hospital opted not to purchase thermal reflective blankets
      because of equivalent performance and minimal cost savings.

PMID- 27692078
TI  - Achieving Cost Reduction Through Data Analytics.
AB  - The reimbursement structure of the US health care system is shifting from a
      volume-based system to a value-based system. Adopting a comprehensive data
      analytics platform has become important to health care facilities, in part to
      navigate this shift. Hospitals generate plenty of data, but actionable analytics
      are necessary to help personnel interpret and apply data to improve practice.
      Perioperative services is an important revenue-generating department for
      hospitals, and each perioperative service line requires a tailored approach to be
      successful in managing outcomes and controlling costs. Perioperative leaders need
      to prepare to use data analytics to reduce variation in supplies, labor, and
      overhead. Mercy, based in Chesterfield, Missouri, adopted a perioperative
      dashboard that helped perioperative leaders collaborate with surgeons and
      perioperative staff members to organize and analyze health care data, which
      ultimately resulted in significant cost savings.

PMID- 27692079
TI  - Body Art and the Perioperative Process.
AB  - Body modification, also known as body art, has been a common cultural practice
      for thousands of years and includes body piercings, transdermal and subdermal
      implants, tattoos, scarification, body stretching and sculpting, dental grills,
      and nail art. Perioperative nurses must learn more about body art to provide
      nonjudgmental, nonprejudicial care and to ensure patient safety when they prepare
      patients for surgery. A welcoming environment engages patients and fosters
      communication so that patients are more likely to share hidden body art. It is
      also necessary for the preoperative nurse to communicate with the perioperative
      team about patients' body art to avoid airway complications, tissue trauma,
      pressure ulcers, burns, postoperative surgical site infections, or distorted
      fluoroscopy or magnetic resonance images. Identifying patients' body art in
      advance allows the perioperative team to be better prepared to deliver safe care.

PMID- 27692080
TI  - Crisis Management of Hypoxia in the OR.

PMID- 27692081
TI  - Antimicrobial Stewardship and Patient Safety.

PMID- 27692082
TI  - Clinical Issues-October 2016.
AB  - Wearing nail polish Key words: nail, polish, UV-cured, gel nail, Shellac.
      Preventing dry skin Key words: dry skin, chapped, dermatitis, hand hygiene.
      Wearing rings Key words: ring, jewelry, wedding ring, band, hand hygiene.

PMID- 27692083
TI  - Evidence appraisal of Winter A, Steurer MP, Dullenkopf A. Postoperative delirium
      assessed by post anesthesia care unit staff utilizing the Nursing Delirium
      Screening Scale: a prospective observational study of 1000 patients in a single
      Swiss institution.: BMC Anesthesiol. 2015;15:184.

PMID- 27692084
TI  - Guideline at a Glance: Surgical Attire.

PMID- 27692085
TI  - Dissecting the Presentation.

PMID- 27692086
TI  - Industry Perspectives: A new online information resource for IPs.

PMID- 27692087
TI  - Reasons for influenza vaccination underutilization: A case-control study.
AB  - BACKGROUND: Influenza vaccines are underused. METHODS: Most (131/140) patients
      from a pediatric practice who were tested for influenza in the 2012-2013 season
      were enrolled. Medical records plus questionnaires determined vaccine and past
      disease histories and influenza vaccine attitudes. Influenza-negative tested
      cases (n = 65) and negative controls (n = 110) closely age-matched to 55 test
      positive cases were compared with influenza-positive cases (n = 66) regarding
      prior influenza, vaccine efficacy, and limited vaccine season conflicting with
      birth dates and preventative visit timing to determine possible validity of
      reasons given for underutilization. RESULTS: The most common parental reason for
      not vaccinating was lack of perceived need. History of previous influenza was
      significantly (P < .0001) associated with disease. Live attenuated vaccine rates
      were greater in controls than in influenza patients for ages 2-18 years (P <
      .005) and for ages 6-18 years (P < .0001), whereas injectable vaccine rates were
      not (P = .30 and P = .60, respectively). Most positive cases (59%) and controls
      (89%) had no prior influenza. CONCLUSIONS: Prior influenza disease may be a risk
      factor for infection that could influence vaccination benefit. Live attenuated
      influenza vaccine outperformed trivalent inactivated influenza vaccine. Limited
      disease experience in individuals with low influenza vaccination rates, along
      with vaccine efficacy limitations, lends validity to some underutilization.

PMID- 27692088
TI  - Introducing In Vivo.

PMID- 27692089
TI  - Immunoproteomic characterization of a Dermatophagoides farinae extract used in
      the treatment of canine atopic dermatitis.
AB  - BACKGROUND: Canine atopic dermatitis is a pruritic allergic skin disease. House
      dust mites have been identified as the main non-seasonal responsible agent.
      Unlike in human allergic patients, groups 1 and 2 antigens have been described as
      minor allergens in dogs, while groups 15 and 18 are considered the major
      allergens. Despite these differences, allergic dogs have traditionally been
      treated using extracts intended for human immunotherapy. OBJECTIVES: To
      investigate the immunological characteristics and the allergen reactivity of dogs
      with atopic dermatitis using a Dermatophagoides farinae commercial extract.
      METHODS: Eighteen dogs diagnosed with atopic dermatitis and 3 healthy control
      dogs from the Iberian Peninsula were included in the study. All the animals were
      older than 12 months, from both sexes and different breeds and showed positive
      specific IgE against D. farinae (>2500 ELISA Absorbance Units). The D. farinae
      allergenic extract used in this study was manufactured and characterized. The
      allergenic profile of the dogs was investigated by immunoblot and specific IgE,
      IgG, IgG1 and IgG2 measured by direct ELISA. Allergen identity was confirmed by
      immunoblot inhibition and mass spectrometry analyses. RESULTS: The results
      confirmed the relevance of groups 15 and 18 antigens, but also groups 1, 2 and
      other medium molecular weight allergens in the sensitization of dogs with atopic
      dermatitis. Immunoblot inhibition and mass spectrometry assays confirmed these
      results. Relevant allergens were quantified by scanning densitometry (Der f 1:
      17MUg/mg, Der f 2: 20.3MUg/mg, Der f 15: 18.1MUg/mg and Der f 18: 9.4MUg/mg).
      Concerning immunoglobulins profile, differences in IgE and IgG1 levels were
      observed between non-atopic and atopic dogs. CONCLUSIONS: The commercial D.
      farinae extract characterized in this study contains the major allergens involved
      in the sensitization of dogs with atopic dermatitis, representing a suitable
      candidate for its use in the diagnosis and immunotherapy of mite allergic dogs.

PMID- 27692090
TI  - Comparison of cytokine responses between dogs with sepsis and dogs with immune
      mediated hemolytic anemia.
AB  - Cytokine abnormalities have been described previously in dogs with varied immune
      mediated and inflammatory conditions such as IMHA and sepsis. The purpose of this
      study was to establish references ranges for cytokine levels in dogs and to
      compare cytokine levels in normal dogs and dogs with two common inflammatory
      diseases (sepsis and IMHA). We hypothesized that cytokine response profiles in
      dogs with sepsis would be significantly different from those in dogs with IMHA
      due to the very different etiologies of the two diseases. Concentrations of 14
      different cytokines in serum were measured and values grouped according to
      cytokine function. Serum from clinically normal dogs was used to establish
      cytokine concentration reference ranges. Rank values for each of the 4 cytokine
      groups were then compared statistically between healthy control, septic and IMHA
      dogs. This analysis revealed differences in cytokine groups between dogs with
      sepsis and IMHA when compared to healthy control dogs but no difference between
      dogs with either of these conditions. In conclustion, dogs in the early stage of
      sepsis and IMHA have similar circulating cytokines despite different etiologies
      suggesting activation of common immunologic pathways. This may have implications
      for immunotherapy of immune mediated diseases in dogs of varying etiology.

PMID- 27692091
TI  - Marek's disease virus immunosuppression alters host cellular responses and immune
      gene expression in the skin of infected chickens.
AB  - Marek's disease virus (MDV), a highly cell-associated lymphotropic alpha
      herpesvirus, is the causative agent of Marek's disease (MD) in domestic chickens.
      MDV replicates in chicken lymphocytes and establishes a latent infection within
      CD4+ T cells. The latently infected CD4+ T cells carry the virus to visceral
      organs, peripheral nerves, and feather follicle epithelium (FFE). FFE is the only
      anatomical site where infectious enveloped cell-free virus particles are produced
      and disseminated into the environment. This study investigated the immunological
      responses and mechanism of viral-induced immunosuppression and immune evasion in
      the FFE. Strong viral replication and lack of a significant number of cytotoxic T
      lymphocytes (CTL) in the infected tissues was prominent. Although the overall
      gene expression pattern was suggestive of a Th1 type immune response, the
      expression levels of several key immune genes were down regulated in the infected
      tissues. The mechanism of MDV-induced immunosuppression appears to be through
      inhibition of CTL function due to down regulation of CD8 glycoprotein and/or
      blocking of CTL migration due to decrease expression of cell adhesion molecules.

PMID- 27692092
TI  - Demonstration of the ability of a canine Lyme vaccine to reduce the incidence of
      histological synovial lesions following experimentally-induced canine Lyme
      borreliosis.
AB  - Lyme disease in dogs can be effectively prevented by vaccination against antigens
      expressed by the spirochete Borrelia burgdorferi during transmission by the tick
      vector Ixodes sp. Lyme vaccine efficacy has traditionally been based on
      indicators of infection following wild-caught tick challenge whereas most other
      types of vaccine are required to demonstrate protection from clinical signs of
      disease. In this vaccination-challenge study we sought to demonstrate the ability
      of a nonadjuvanted, outer surface protein A (OspA) vaccine to protect from
      infection and to prevent synovial lesions consistent with Borreliosis. Thirty,
      purpose-bred beagles were randomly divided into vaccinated and unvaccinated
      groups. The vaccinated group was administered two subcutaneous doses of a
      nonadjuvanted, purified, Borrelia burgdorferi OspA vaccine at a 21- day interval.
      Dogs were challenged by wild-caught, B. burgdorferi-infected ticks (Ixodes
      scapularis). Clinical signs, serology, Borrelia isolation and PCR evaluated
      antemortem vaccine efficacy. Postmortem histopathological analysis of synovial
      tissue was compared to antemortem infection status. Borreliosis was demonstrated
      by Borrelia isolation from skin biopsies in 13 out of 15 unvaccinated dogs. All
      unvaccinated dogs' Western blot profiles were consistent with infection. Two of
      15 vaccinated dogs had at least one positive spirochete culture which cleared
      91days post-challenge, and Western blot profiles were consistent with vaccination
      alone. No dogs, vaccinated or unvaccinated, exhibited clinical signs consistent
      with borreliosis. Based on a histopathological cumulative joint scoring system
      (CJS), all unvaccinated dogs had synovial lesions indicative of Lyme disease.
      Only one of the vaccinated dogs had a CJS that was greater than the statistical
      cut off score for the absence of synovial lesions. There was high correlation
      between clinical histopathology and spirochete isolation. Infection with B
      burgdorferi may produce inconsistent clinical signs of lameness.
      Histopathological changes in joints from infected dogs are reliable indicators of
      borreliosis and correlate well with other indicators of infection. This model
      provides support that vaccination with a nonadjuvanted, purified OspA vaccine
      offers protection from Borrelia infection and the resulting synovial lesions that
      can lead to clinical signs of lameness.

PMID- 27692093
TI  - Multinucleated giant cell cytokine expression in pulmonary granulomas of cattle
      experimentally infected with Mycobacterium bovis.
AB  - Regardless of host, pathogenic mycobacteria of the Mycobacterium tuberculosis
      complex such as Mycobacterium bovis, induce a characteristic lesion known as a
      granuloma, tubercle or tuberculoid granuloma. Granulomas represent a distinct
      host response to chronic antigenic stimuli, such as foreign bodies, certain
      bacterial components, or persistent pathogens such as M. bovis. Granulomas are
      composed of specific cell types including epithelioid macrophages, lymphocytes
      and a morphologically distinctive cell type, the multinucleated giant cell.
      Multinucleated giant cells are formed by the fusion of multiple macrophages;
      however, their function remains unclear. In humans, giant cells in tuberculous
      granulomas have been shown to express various cytokines, chemokines and enzymes
      important to the formation and maintenance of the granuloma. The objective of
      this study was to quantitatively assess multinucleated giant cell cytokine
      expression in bovine tuberculoid granulomas; focusing on cytokines of suspected
      relevance to bovine tuberculosis. Using calves experimentally infected with M.
      bovis, in situ cytokine expression was quantitatively assessed using RNAScope(r)
      for the following cytokines TNF-alpha, IFN-gamma, TGF-beta, IL-17A and IL-10.
      Multinucleated giant cells in bovine tuberculoid granulomas expressed all
      examined cytokines to varying degrees, with differential expression of TGF-beta,
      IL-17A and IL-10 in giant cells from early versus late stage granulomas. There
      was a modest, positive correlation between the level of cytokine expression and
      cell size or number of nuclei. These results suggest that multinucleated giant
      cells are active participants within bovine tuberculoid granulomas, contributing
      to the cytokine milieu necessary to form and maintain granulomas.

PMID- 27692094
TI  - Macrophage effector responses of horses are influenced by expression of CD154.
AB  - Reactive intermediates contribute to innate immunity by providing phagocytes with
      a mechanism of defense against bacteria, viruses and parasites. To better
      characterize the role of CD154 in the production of reactive intermediates, we
      cloned and expressed recombinant equine CD154 (reqCD154) in Chinese Hamster Ovary
      (CHO). In co-culture experiments, CHO cells ectopically expressing reqCD154
      elicited superoxide production in monocyte-derived macrophages (MDM).
      Collectively, our results indicate that regulation of CD154 expression plays a
      role in innate host defenses.

PMID- 27692095
TI  - Screening scFv antibodies against infectious bursal disease virus by co
      expression of antigen and antibody in the bacteria display system.
AB  - We have previously reported an antigen and antibody co-expression (AAC)
      technology to demonstrate the interaction between a known antigen and antibody.
      To validate the co-expression system for screening antibody libraries, a single
      chain fragment variable(scFv)antibody library was constructed from chickens
      immunized with the VP2 protein of infectious bursal disease virus (IBDV). The
      genes of both VP2 and scFv antibodies were inserted into the pBFD-Ab-Ag vector.
      The co-expression library was subjected to three rounds of screening by flow
      cytometry (FCM) using a polyclonal antibody against VP2 through a bacteria
      display system. We achieved enrichment of scFv specific for IBDV. 110 individual
      clones were initially selected and sequenced. Twenty clones were selected based
      on fluorescence intensity by FCM. The scFv antibodies were expressed by pET-27b
      in E.coli and purified. The specificity and affinity of the selected scFv
      antibodies were confirmed by western blotting assay and ELISA analysis. What's
      more, the neutralizing capacity was measured with IBDV-B87(100 TCID50) in vitro.
      Four scFvs (clone 8(1), Y8, L10 and L7) showed significant neutralizing capacity.
      Two of the four scFvs (clone 8(1) and Y8) demonstrated a higher neutralizing
      activity to IBDV-B87 and the titers were 16,384 and 8,192, respectively. The two
      scFvs had higher neutralizing capacity than those obtained in previous studies.
      We demonstrated that the AAC technology could be applied to screen antibody
      libraries without baiting antigen to make antibody screening process easier and
      obtain scFvs with higher neutralizing capacity.

PMID- 27692096
TI  - Haemophilus parasuis vaccines.
AB  - Glasser's disease, which is caused by Haemophilus parasuis, is a major threat to
      swine throughout the world. At present, the predominant method of controlling
      this disease is through vaccination with an inactivated vaccine, which has many
      limitations. For example, there is no available method to differentiate between
      infected and vaccinated animals. In addition, inactivated vaccines do not contain
      all of the virulent serovars that circulate in a region. Additionally, novel
      vaccines that address the shortcomings of inactivated vaccines are not available.
      Here, we summarize existing knowledge concerning H. parasuis vaccines, and
      provide some suggestions that may help to improve H. parasuis vaccines.

PMID- 27692097
TI  - Secretory immunoglobulin A and immunoglobulin G in horse saliva.
AB  - This study aimed to increase the knowledge on salivary antibodies in the horse
      since these constitute an important part of the immune defence of the oral
      cavity. For that purpose assays to detect horse immunoglobulin A (IgA) including
      secretory IgA (SIgA) were set up and the molecular weights of different
      components of the horse IgA system were estimated. Moreover, samples from 51
      clinically healthy horses were tested for total SIgA and IgG amounts in saliva
      and relative IgG3/5 (IgG(T)) and IgG4/7 (IgGb) content were tested in serum and
      saliva. Results showed a mean concentration of 74MUg SIgA/ml horse saliva and
      that there was a large inter-individual variation in salivary SIgA concentration.
      For total IgG the mean concentration was approx. 5 times lower than that of SIgA,
      i.e. 20MUg IgG/ml saliva and the inter-individual variation was lower than that
      observed for SIgA. The saliva-serum ratio for IgG isotypes IgG3/5 and IgG4/7 was
      also assessed in the sampled horses and this analysis showed that the saliva
      serum ratio of IgG4/7 was in general approximately 4 times higher than that of
      IgG3/5. The large inter-individual variation in salivary SIgA levels observed for
      the normal healthy horses in the present study emphasises the need for a large
      number of observations when studying this parameter especially in a clinical
      setting. Moreover, our results also indicated that some of the salivary IgG does
      not originate from serum but may be produced locally. Thus, these results provide
      novel insight, and a base for further research, into salivary antibody responses
      of horses.

PMID- 27692098
TI  - Effects of choline treatment in concentrations of serum matrix metalloproteinases
      (MMPs), MMP tissue inhibitors (TIMPs) and immunoglobulins in an experimental
      model of canine sepsis.
AB  - The aim of the present study was to investigate effects of intravenous (i.v.)
      choline treatment on serum matrix metalloproteinases (MMP), MMP tissue inhibitors
      (TIMP) and immunoglobulins (Igs), and to determine if there were relations
      between serum MMPs/TIMPs and C-reactive protein (CRP) (as a marker of the acute
      phase response), immunoglobulin G and M (IgG and IgM) (as a maker of the Ig
      responses) and markers of organ damage such as muscular damage (creatine
      phosphokinase, [CPK]), liver damage (alanine aminotransferase [ALT]) and renal
      dysfunction (blood urea nitrogen [BUN] and creatinine, [Cr]) in dogs with
      endotoxemia. Healthy dogs (n=24) were randomized to Saline, Choline (C),
      Lipopolysaccharide (LPS), and LPS+C groups and received 0.9% NaCl (5mL/i.v.),
      choline chloride (20mg/kg/i.v.), LPS (0.02mg/kg/i.v.) and LPS (0.02mg/kg/i.v.)
      plus choline chloride (20mg/kg/i.v.), respectively. Serum MMPs and TIMPs
      concentrations were analyzed by commercial ELISA kits. MMP and TIMP increased at
      1-48h (P<0.05), whereas IgG and IgM decreased at 24-48h in LPS group, compared to
      their baselines. Choline treatment reduced changes in serum MMPs, TIMPs and
      markers of organ damage, and prevented the hypoimmunoglobulinemia in LPS+C. MMPs
      and TIMPs were correlated positively (P<0.05) with serum CRP, CPK, ALT, BUN and
      Cr, but not with serum Igs. Our findings suggest that the serum MMPs, TIMPs and
      Igs are involved in the pathophysiology of endotoxemia, and MMPs and TIMPs are
      correlated with the acute phase reaction and multi-organ failure. In addition, we
      demonstrated a direct effect of choline administration in decreasing serum MMPs
      and TIMPs, and preserving serum Igs in the course of endotoxemia.

PMID- 27692099
TI  - [2016 - European Society of Hypertension Guidelines for the management of high
      blood pressure in children and adolescents].

PMID- 27692100
TI  - Orthopaedic trauma clinical and basic science research in Spain: An update.

PMID- 27692101
TI  - Application of calcium phosphates and fibronectin as complementary treatment for
      osteoporotic bone fractures.
AB  - INTRODUCTION: The gradual aging of the population results in increased incidence
      of osteoporotic bone fractures. In a good quality bone, the fixation with the
      usual methods is adequate, but not in osteoporotic bone, in which consolidation
      delays and other complications are common, with failure rates for screws up to
      25%. OBJECTIVE: To test fibronectin loaded hydroxyapatite as a complementary
      treatment for osteoporotic fractures. MATERIAL AND METHODS: This study was
      performed in a vivo model; 42 female osteoporotic adult rabbits 4-5kg (White New
      Zealand) were used. Two groups (hydroxyapatite and fibronectin loaded
      hydroxyapatite) and a control group were tested. 3 time points 24h, 48h and 5days
      were studied. Defects were created in both femurs, in one of them, a cannulated
      screw (4mm) and a biocompatible material were placed; in the other femur a screw
      was inserted without supplemented material forming the control group.
      Osteoporosis was induced from models already known throughout administration of
      steroids. Samples were analyzed histologically and through imaging (micro Ct).
      RESULTS: Basal levels of BMD are observed below to normal when compared to other
      studies (0.25/0.3 instead of 0.4). Global and dependent of time analysis of
      samples, show no significant differences for samples analyzed. However, an
      important trend was noted for variables that define the trabecular bone
      microarchitecture. Indices that define trabecular microarchitecture in the
      comparative analysis found to have statistical differences (p<0.01). DISCUSSION:
      Osteosynthesis in an osteoporotic bone is a challenge for the surgeon, due to a
      reduced bone mineral density and different bone architecture. The main finding
      was the verification of the hypothesis that the trabecular bone parameters
      increases with our augmentation material in weak rabbit bone quality. Also, the
      histological analyses of samples show an increase of non inflammatory cells in
      protein samples (OHAp-Fn) from the first 24hours. CONCLUSION: An early response
      of rabbit osteroporotic bone to a complementary treatment with fibronectin loaded
      hydroxyapatite has been observed. This response is reflected in greater values
      for indices that define the trabecular bone microarchitecture, thickness and
      separation, a greater non-inflammatory cellularity after only 24hours and an
      increased amount of connective tissue observed at 48hours.

PMID- 27692102
TI  - Minimally invasive polyaxial locking plate osteosynthesis for 3-4 part proximal
      humeral fractures: our institutional experience.
AB  - INTRODUCTION: The objectives of this study were to describe the surgical
      technique of fixation of 3-4 part proximal humeral fractures with polyaxial
      locking plates utilising a minimally invasive approach and to evaluate the
      accuracy of reduction and stability of fixation. PATIENTS AND METHODS: We
      retrospectively reviewed 90 patients. Fractures were classified according to the
      Neer classification system. Different radiological parameters were measured to
      assess the quality of reduction and the stability of fixation. Complications and
      clinical outcomes were evaluated after one year of minimum follow up. RESULTS:
      There were 76 women and 14 men, with a mean age of 67.4years +/-13 (range, 29
      85). There were 60 3-part and 30 4-part fractures. Frozen cancellous allograft
      was used in 30 cases (33.3%). All fractures progressed to union and at one year
      follow up, the mean Constant score was 79.6+/-12(range, 62-100). Mean forward
      flexion, abduction, external rotation and internal rotation were 155 degrees ,
      148 degrees , 39 degrees  and vertebra Dorsal 8, respectively. Complications were
      noted in seven patients while the postoperative "head-diaphysis angle", "greater
      tuberosity height" and "medial metaphysis reconstruction" were close to the
      anatomical parameters; no significant differences were noted at one year
      radiological follow up. CONCLUSION: Reliable and stable fixation can be expected
      with the use of polyaxial locking plate through a minimally invasive approach for
      the treatment of 3-4 part proximal humeral fractures. Satisfactory functional
      results for this procedure can be obtained.

PMID- 27692104
TI  - Effect of cefazolin and cefuroxime on fracture healing in rats.
AB  - OBJECTIVE: To determine the effect of cefazolin and cefuroxime (the two most
      commonly used beta lactam antibiotics) at therapeutic doses in fracture healing
      in an animal model. MATERIAL AND METHODS: 75 adult male wistar rats (3months old)
      were selected. They were divided into three groups of 25 animals each (placebo,
      cefazolin and cefuroxime). A closed fracture was made in the middle third of the
      right femur of each rat and fixed with a Kirschner wire. Each group was treated
      with either saline (placebo), cefazolin or cefuroxime at therapeutic doses during
      fracture healing. Four weeks after fracture rats were killed and femora analysed
      through mechanical and histological testing. RESULTS: The group treated with
      cefuroxime showed a lower mechanical resistance of the healing callus and a lower
      histological grade than placebo. The group treated with cefazoline showed a
      similar mechanical resistance and histological grade of callus to placebo.
      CONCLUSION: Cefuroxime appear to disturb fracture healing more than cefazolin or
      placebo in Wistar rats. If those results are similar to human, the use of
      cefuroxime during fracture healing should be avoided in the clinical setting, if
      possible.

PMID- 27692103
TI  - Comminuted fractures of the radial head: resection or prosthesis?
AB  - INTRODUCTION: At present, surgical treatment of comminuted radial head fractures
      without associated instability continues to be controversial. When anatomical
      reconstruction is not possible, radial head excision is performed. However, the
      appearance of long-term complications with this technique, along with the
      development of new radial head implants situates arthroplasty as a promising
      surgical alternative. The purpose of the present study was to compare the mid
      term functional outcomes of both techniques. MATERIALS AND METHODS: A
      retrospective study was performed between 2002 and 2011 on 25 Mason type-III
      fractures, 11 patients treated with primary radial head resection and 14 who
      received treatment of the fracture with metal prosthesis. At the end of follow
      up, patients were contacted and outcomes evaluated according to: Mayo Elbow
      Performance Score (MEPS), the Disabilities of the Arm, Shoulder and Hand score
      (DASH) and strength measurement. Radiographic assessment (proximal migration of
      the radius, osteoarthritic changes, and signs of prosthesis loosening) was also
      performed. RESULTS: The average age of the sample was 53.7 years in the resection
      group, and 54.4 years in the replacement group, with a mean follow-up of 60.3 and
      42 months respectively. According to the MEPS scale, there were 6 excellent
      cases, 3 good and 2 acceptable in the resection group, and 6 excellent cases, 3
      good, 3 acceptable, and 2 poor in the prosthesis group. The mean DASH score were
      13.5, and 24.8 for the resection and the replacement group respectively. We found
      one postoperative complication in the resection group (stiffness and valgus
      instability) and 6 in the replacement group: 3 of joint stiffness, 1 case of
      prosthesis breakage, and 2 neurological injuries. CONCLUSIONS: Although this is a
      retrospective study, the high complication rate occurring after radial head
      replacement in comparison with radial head resection, as well as good functional
      results obtained with this last technique, leads us to recommend it for
      comminuted radial head fractures without associated instability.

PMID- 27692105
TI  - Large fracture of the anteromedial tibial plateau with isolated posterolateral
      knee corner injury: case series of an often missed unusual injury pattern.
AB  - Tibial plateau fractures are a heterogeneous group of lesions with multiple
      fracture patterns. They are often associated with soft tissue injuries, the
      lateral meniscus and the anterior cruciate ligament (ACL) being the most common
      structures affected. The purpose of this article is to present a case series of
      an often missed unusual injury pattern that consists on the association of a
      large anteromedial tibial plateau fracture with a posterolateral (PL) knee corner
      injury without involvement of the cruciate ligaments. The diagnosis of PL complex
      injury may go unrecognized in a considerable number of cases and delay on the
      treatment decreases the success rate of soft tissue repairing. The importance of
      a high index of suspicion and a proper early diagnosis with an MRI is of
      paramount importance. We also describe the current surgical management used by
      the authors and review of the current literature.

PMID- 27692106
TI  - Whole-exome sequencing analysis in twin sibling males with an anterior cruciate
      ligament rupture.
AB  - Familial predisposition is among the major genetic risk factors for non-contact
      musculoskeletal tissue injuries. Personal genome sequence shows that different
      polymorphism profiles may account for the number and the degree of injuries and
      the recovery time. Genotyping studies allow investigation into genome factors
      with potential impact on pathogenesis of non-contact ligament injuries. We have
      studied a family with twin sibling males surgically diagnosed of an anterior
      cruciate ligament non-contact rupture and non-affected progenitors (father and
      mother) were subjected to whole exome sequencing (WES) analysis. WES analysis
      previously carried out on 16 individuals, without ACL injury medical records,
      were also included in this study for single nucleotide variants (SNVs) and small
      insertions and deletions detection (indels), variant filtering and to prioritize
      variants relative to the disease. WES analysis to identify SNVs and indels was
      performed using open web-based bioinformatics tools. A set of 11 new variants
      shared by family members can be associated to ACL non-contact injury, including
      SerpinA11, ARSI, NOCHT4, EPB41, FDFT1, POMC, KIF26A, OLFML2B, ATG7, FAH and WDR6.
      All of them, except ATG7 and WDR6, have shown a damaging predictive pattern by
      combinatorial standard predictive scores. In combination to the identified SNVs
      of EPB41 and SerpinA11 genes, ACTL7A gene showed a predicted deleterious variant
      reinforcing the idea these variants impact on of fibroblast-like cells
      deformability and ECM misbalance, Differential gene expression and RNA sequencing
      analysis will help to understand the combined participation of these protein
      coding genes in ACL non-contact injuries.

PMID- 27692107
TI  - Predictive variables of open reduction in intertrochanteric fracture nailing: a
      report of 210 cases.
AB  - BACKGROUND: Factors that impede closed reduction in intertrochanteric fractures
      remain unknown. This study was designed with the aim of establishing radiological
      variables that can predict an open reduction when nailing those type of
      fractures. MATERIALS AND METHODS: Observational prospective study carried out
      between March 2013 and March 2015. Patients of both gender who suffered an
      intertrochanteric fracture, and who were surgically treated by intramedullary
      nailing (PFN-A), were included. Patients were evaluated by means of a
      questionnaire designed in 12 de Octubre Trauma department. Radiological
      parameters assessed preoperatively, after fracture reduction in the traction
      table, and after fixation were: calcar, lateral wall and posterior buttress
      integrity or disruption; lesser trochanter location, varus or valgus deformities,
      and flexion or extension of the proximal fragment. RESULTS: Association between
      open reduction and the following types of fractures was statistically significant
      (p<0.001): subtypes A2.3, A3.2 and A3.3 of AO classification and subtypes IV and
      V of Evans classification. There were four radiological parameters associated
      with the need for open reduction: disruption of lateral wall (p<0.0000),
      posterior wall fracture (p<0.001), calcar (p<0.004) and malalignment in the axial
      view (p<0.001). CONCLUSIONS: Open reduction seems to be necessary for complex
      fracture patterns such as A2.3, A3.2 and A3.3 types of AO/OTA classification, as
      well as types IV and V of Evans classification. There are four major radiological
      parameters that can predict the need of approaching the fracture site: posterior
      buttress, calcar disruption, lateral wall disruption and proximal fragment
      flexion. The development of high quality evidence regarding this topic is
      necessary due to the vast impact that open reduction can have on elderly
      patients.

PMID- 27692108
TI  - Surgical delay as a risk factor for wound infection after a hip fracture.
AB  - PURPOSE: Analysis of significant risk factors for mortality and for medical and
      orthopaedic complications. PATIENTS AND METHODS: Observational study of a
      prospective consecutive cohort of 697 patients diagnosed of hip fracture from
      December 2012 to December 2014. Average age was 85+/-9years and 520 were female
      (75%). Intracapsular fractures (308, 44%) were treated non-operatively, (19
      patients), with cannulated screws (58) or with hip arthroplasty (228 bipolar, 3
      total hip atrhoplasty). Extracapsular fractures (389, 56%) were reduced and fixed
      with 375 trochanteric nails and 14 sliding-hip-screw-plates. Patients were
      controlled clinically and radiographically in outpatient clinic after 1, 3, 6 and
      12months. Bivariate analysis (Pearson, Mann-Whitney, Wilcoxon) was applied to
      study statistically significant relations, and Odds Ratio were calculated.
      RESULTS: Surgical delay reached 2.1+/-2.2days, 1.7+/-1.9 in medically stable
      patients. Main reason for delay was anticoagulant/anti-platelet therapy.
      Immediate weight-bearing was begun for 72% of patients. Average time in-hospital
      was 12+/-8days and 63% returned to previous environment. Lost-to-follow-up
      reached 4% after 1month and 8% after 6months. After 1year, 6% of previously
      walking patients were unable to walk. Mortality reached 4% while in-hospital and
      14% after 1year, with older age as only significant risk factor (p=0.004),
      OR=1.9. Wound infection developed in 2.3% of the series, and surgical delay
      longer than 24hours was a significant risk factor (p=0.023), with an OR=3.48 (1.1
      10.8). Fixation failed in 7.9% of cannulated screws and 1.9% of trochanteric
      nails (1.1% cut-out, 0.8% nail fracture), while 2.7% of arthroplasty patients
      suffered a prosthesis dislocation and 1.3% a periprosthetic fracture.
      Pyelonephritis appeared in 6.7%, pneumonia in 6.3% and cardiac failure in 2.2% of
      patients; significant risk factors were previous comorbidity for pneumonia
      (p=0.007) (OR=2.7) and cardiac failure (p=0.007) (OR=9.7), as well as older age
      (p=0.006) (OR=2.2) for pneumonia. CONCLUSIONS: Surgical delay longer than 24hours
      has been an important risk factor for wound infection, a finding not previously
      described in literature. Older age is a significant risk factor for mortality and
      pneumonia, and previous comorbidity for cardiac failure and pneumonia.

PMID- 27692110
TI  - Necrotising fasciitis of the extremities: implementation of new management
      technologies.
AB  - INTRODUCTION: Necrotising fasciitis (NF) is potentially life-threatening soft
      tissue infection. Early diagnosis and aggressive surgical debridement are
      critical to decrease mortality and morbidity. The impacts of new management
      technologies such as hydro-bisturi-assisted debridement (HAD) and negative
      pressure wound therapy (NPWT) are not yet clear with respect to treatment of NF.
      The objective of this study was to describe laboratory (including LRINEC score),
      clinical and microbiological factors, treatment methods and outcomes related to
      managing necrotising fasciitis, focusing on the implementation of new treatment
      methods in our centre. METHODS: From June 2010 to June 2014, adult patients
      diagnosed with necrotising fasciitis affecting an upper or lower limb that were
      admitted to our hospital, a referral tertiary care centre, were eligible to
      participate in this study. Demographic data, clinical features, location of
      infection, Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score on
      the day of admission, microbiology and laboratory results, use of HAD, wound
      management using NPWT, and patient outcomes were retrospectively analysed. A
      univariate risk factor analysis was performed, in an attempt to define prognostic
      factors for mortality. RESULTS: A total of 20 patients satisfied the inclusion
      criteria. Type II NF (Group A beta-haemolytic streptococci) was found in 8 cases
      (40%). The average LRINEC score on the day of admission was 6. The lower
      extremity was affected in 60% of the cases. All patients were treated
      operatively, with 2.5 interventions on average. Hydro-bisturi was used in the
      first debridement in 40% of the cases (8 out 20). In 75% of the studied cases,
      Negative Pressure Wound Therapy (NPWT) was the technique selected for surgical
      wound management. The global mortality rate was 30%. On univariate analysis, the
      only factors significantly associated with mortality were high levels of
      creatinin (p=0.033) and low blood glucose levels (p=0.012). Finally, four
      amputations were observed in this series. CONCLUSION: We confirm that necrotising
      fasciitis (NF) of the extremities, despite new advancements in treatment and
      critical care management, is still a potentially life-threatening soft-tissue
      infection (30% mortality). New, advanced wound management modalities have been
      heavily used in management of necrotising fasciitis, but these have not had
      significant impacts on morbidity and mortality rates.

PMID- 27692109
TI  - Age-related injury patterns in Spanish trauma ICU patients. Results from the
      RETRAUCI.
AB  - BACKGROUND: Injury patterns may differ in trauma patients when age is considered.
      This information is relevant in the management of trauma patients and for
      planning preventive measures. METHODS: We included in the study all patients
      admitted for traumatic disease in the participating ICUs from November 23rd, 2012
      to July 31st, 2015 with complete records. Data on epidemiology, injury patterns,
      severity scores, acute management, resources utilisation and outcome were
      recorded and compared in the following groups of age: <=55years (young adults),
      56-65 years (adults), 66-75 years (elderly), >75years (very elderly).
      Quantitative data were reported as median (Interquartile Range (IQR) 25-75) and
      categorical data as number and percentage. Comparison between groups of age with
      quantitative variables was performed using the analysis of variance (ANOVA) test.
      Differences between groups with categorical variables were compared using the chi
      square test. A value of p<0.05 was considered significant. RESULTS: We included
      2700 patients (78.9% male). Median age was 46 (31-62) years. Blunt trauma was
      present in 93.7% of the patients. Median RTS was 7.55 (5.97-7.84). Median ISS was
      20 (13-26). High-energy trauma secondary to motor-vehicle accident with
      rhabdomyolysis and drugs abuse showed an inverse linear association with ageing,
      whilst pedestrian falls with isolated brain injury, being run-over and pre-injury
      antiplatelets or anticoagulant treatment increased with age (in all cases
      p<0.001). Multiple injuries were more common in young adults (p<0.001). Acute
      kidney injury prevalence was higher in elderly and very elderly patients
      (p<0.001). ICU Mortality increased with age in spite of similar severity scores
      in all groups (p<0.001). The main cause of death in all groups was intracranial
      hypertension. CONCLUSIONS: Different injury patterns exist in relation with
      ageing in trauma ICU patients. Adult patients were more likely to present high
      energy trauma with significant injuries in different areas whilst elderly
      patients were prone to low-energy falls, complicated by antiplatelets or
      anticoagulants use, resulting in severe brain injury and increased mortality.

PMID- 27692111
TI  - Histological evolution of the regenerate during bone transport: an experimental
      study in sheep.
AB  - INTRODUCTION: Bone transport (BT) for segmentary bone defects is a well-known
      technique as it enables correction with new bone formation, which is similar to
      the previous bone. Despite the high number of experimental studies of distraction
      osteogenesis in bone lengthening, the types of ossification and histological
      changes that occur in the regenerate of the bone transport process remain
      controversial. OBJECTIVE: The aim of this study is to provide the complete
      evolution of tissues and the types of ossification in the regenerate during the
      different phases of bone formation after BT until the end of the remodelling
      period. METHODS: A histological study was performed using ten adult sheep that
      were submitted to BT. The types of ossification as well as the evolution of
      different tissues in the regenerate were determined using histomorphometry and
      inmunohistochemical studies. The evolution of trabeculae thickness, osteoblast
      and osteoclast densities, relationship between collagen types and changes in
      vascularization were also studied. RESULTS: Ossification was primarily
      intramembranous, with some focus of endochondral ossification in isolated
      animals. The cell counts showed a progression of cellular activity from the
      periphery to the centre, presenting the same progression as the growth of bone
      trabeculae, whose trabeculae thickness was quadrupled at the end of remodelling.
      Inmunohistochemical studies confirmed the prevalence of type I collagen and the
      ratio of the Type I/Type II collagen ratio was found to be 2.48. The percentages
      of the vascularized areas were proximally higher than distally in all animals,
      but distal zone obtained higher rates than the central region. CONCLUSIONS: Bone
      transport regenerate exhibits a centripetal ossification model and a mixed
      pattern with predominance of intramembranous over endochondral ossification. The
      data obtained resemble partially to those found in models of bone lengthening
      applied to large animals. This study provides a detailed structural
      characterization of the newly formed tissue, which may help to explain the
      development of the regenerate of bone transport in humans. It will also serve for
      future mechanobiological models that may aid research on the effect of loading or
      distractor stiffness in clinical results.

PMID- 27692112
TI  - Is cannulated-screw fixation an alternative to plate osteosynthesis in open book
      fractures? A biomechanical analysis.
AB  - OBJECTIVES: The current biomechanical work compares the symphyseal and sacroiliac
      stability obtained with two systems of bone osteosynthesis. The two methods of
      fixation compared were the 6-hole suprapubic non-locked plate and pubic fixation
      with two cannulated screws, a novel technique that can be applied percutaneously
      in the clinical practice. The aim of this study was to examine the validity of
      the use of two-cannulated-screws osteosynthesis in order to minimize the
      secondary effects of open fixation, especially in patients in whom an open
      reduction is contraindicated. MATERIALS AND METHODS: A biomechanical study was
      designed in 9 fresh, human pelvis specimens, simulating an AO B1.1 type injury,
      using both fixation systems sequentially in each specimen. In both parts of the
      test, the specimens were subjected to an axial load of 300N. Displacements and
      rotations between the different pelvic elements were studied by means of a
      discrete set of points. The absence of differences between the two systems has
      been set as the null hypothesis. RESULTS: There were significant differences in
      favor of the cross-cannulated screws in most of the displacements measured at the
      pubic symphysis and sacroiliac joint. CONCLUSIONS: Fixation of the AO B1.1 type
      fractures with cross cannulated screws restores the biomechanical behavior of the
      pubic symphysis, obtaining better stability than fixation with the 6-hole non
      locked plate. To date, no comparative, biomechanical studies have been conducted
      with these two systems of osteosynthesis. This study demonstrates that cross
      cannulated screws fixation of the pubic symphysis in AO B1.1 pelvic fractures
      should be considered as an alternative to the conventional plating system.

PMID- 27692113
TI  - Allograft plus OP-1 enhances ossification in posterolateral lumbar fusion: A
      seven year follow-up.
AB  - PURPOSE: To study the results of the combination of allograft plus BMP-7 in
      comparison with allograft alone in posterolateral lumbar arthrodesis. PATIENTS
      AND METHODS: A blinded controlled consecutive prospective cohort of skeletally
      mature patients study. One hundred and ten patients underwent posterolateral
      lumbar instrumented arthrodesis. Allograft randomly compacted onto either the
      right or the left side of the articular and the posterior aspect of the
      transverse processes of lumbar spine. The same procedure performed on the
      contralateral side, but allograft was previously mixed with osteogenic protein
      (OP-1). Clinical, x-ray and CT-scan long follow-up performed. Univariable and
      multivariable logistic regression analyses. RESULTS: More bone continuity was
      found with allograft plus OP-1 than with allograft alone (p>0.0038). The amount
      of bone mass was greater on the OP-1 side (p<0.001). No local or systemic adverse
      effect were noted. CONCLUSIONS: Allograft on one side plus allograft with BMP-7
      on the other achieved a fusion rate of 93 per cent. Allograft combined with BMP-7
      was more effective than allograft alone.

PMID- 27692114
TI  - The Jim Pattison-Mazankowski Alberta Heart Institute Cardiac Rehabilitation
      Symposium: A Call to Exercise and Risk Reduction.

PMID- 27692116
TI  - Ensuring Cardiac Rehabilitation Access for the Majority of Those in Need: A Call
      to Action for Canada.
AB  - Cardiac rehabilitation (CR) is a proven model of secondary prevention. Indicated
      cardiac conditions for CR are well established, and participation of these
      patients results in significantly lower mortality and morbidity when compared
      with usual care. There are approximately 170 CR programs in Canada, which varies
      widely by province. There is a grossly insufficient capacity to treat all
      patients with cardiac indications in Canada and beyond. The density of CR
      services is about half that in the United States, at 1 program per 208,823
      inhabitants or 1 program per 7779 patients with cardiac disease. Despite the
      Canadian Cardiovascular Society's target of 85% referral for CR for cardiac
      inpatients with the appropriate indications, significantly fewer patients are
      referred for CR. Moreover, certain patient groups-such as women, ethnocultural
      minorities, and those of low socioeconomic status-are less likely to access CR,
      despite greater need because of poorer outcomes. CR appears to be reaching a
      healthier population that is perhaps more adherent to secondary prevention
      recommendations and hence in less need of the limited CR spots available. The
      reasons for CR underuse are well established and include factors at patient,
      referring provider, CR program, and health system levels. A Cochrane review has
      established some effective interventions to increase CR use, and these must be
      implemented more broadly. We must advocate for CR reimbursement. Finally, we must
      reallocate our CR resources to patients with the greatest need. This may involve
      risk stratification, with subsequent allocation of lower-risk patients to a more
      widely available, lower-cost, and effective alternative model of CR.

PMID- 27692117
TI  - Impact of Cardiac Rehabilitation and Exercise Training on Psychological Risk
      Factors and Subsequent Prognosis in Patients With Cardiovascular Disease.
AB  - The role of psychological risk factors has been under-recognized in most
      subspecialties of medicine, as well as in general medicine practices. However,
      considerable evidence indicates that psychosocial factors are involved in the
      pathogenesis and progression of cardiovascular disease (CVD). Emerging data from
      cardiac rehabilitation (CR) settings and CR exercise training (CRET) programs
      have demonstrated the value of comprehensive CRET to improve psychological
      functioning and reduce all-cause mortality. Recent evidence also supports the
      role of CRET and the added value of stress management training in the secondary
      prevention of CVD.

PMID- 27692115
TI  - Comprehensive Cardiovascular Risk Reduction and Cardiac Rehabilitation in
      Diabetes and the Metabolic Syndrome.
AB  - The epidemic of obesity has contributed to a growing burden of metabolic syndrome
      (MetS) and diabetes mellitus (DM) worldwide. MetS is defined as central obesity
      along with associated factors such as hypertriglyceridemia, low high-density
      lipoprotein cholesterol, hyperglycemia, and hypertension. MetS and DM are
      associated with significant cardiovascular morbidity and mortality. Healthy
      behavioural modification is the cornerstone for reducing the atherosclerotic
      cardiovascular disease burden in this population. Comprehensive,
      multidisciplinary cardiac rehabilitation (CR) programs reduce mortality and
      hospitalizations in patients with MetS and DM. Despite this benefit, patients
      with MetS and DM are less likely to attend and complete CR because of numerous
      barriers. Implementation of innovative CR delivery models might improve
      utilization of CR and cardiovascular outcomes in this high-risk population.

PMID- 27692119
TI  - Heart Failure: Exercise-Based Cardiac Rehabilitation: Who, When, and How Intense?
AB  - The primary chronic symptom in patients with clinically stable heart failure (HF)
      is reduced exercise tolerance, measured as decreased peak aerobic power (peak
      oxygen consumption [Vo2]), and is associated with reduced quality of life and
      survival. Exercise-based cardiac rehabilitation (EBCR) is a safe and effective
      intervention to improve peak Vo2, muscle strength, physical functional
      performance, and quality of life and is associated with a reduction in overall
      and HF-specific hospitalization in clinically stable patients with HF. Despite
      these salient benefits, fewer than one-tenth of eligible patients with HF are
      referred for EBCR after hospitalization. In this review, selection for and timing
      of EBCR for patients with HF, as well as exercise prescription guidelines with
      special emphasis on the optimal exercise training intensity to improve peak Vo2,
      are discussed.

PMID- 27692118
TI  - Rehabilitation Therapy in Peripheral Arterial Disease.
AB  - Peripheral arterial disease (PAD) is the result of atherosclerosis in the lower
      limb arteries, which can give rise to intermittent claudication (IC), limb
      ulceration, infections, and, in some circumstances, amputation. As a result of
      PAD, patients are frequently limited in both walking duration and speed. These
      ambulatory deficits impact both functional capacity and quality of life. The
      prevalence of PAD is increasing, and patients with this diagnosis have high
      cardiovascular morbidity and mortality. A comprehensive approach is required to
      improve outcomes in patients with PAD and include tobacco cessation,
      pharmacologic management of metabolic fitness, risk-factor modification, and
      exercise training. Supervised exercise programs significantly improve functional
      capacity and quality of life in addition to reducing IC. These programs reduce
      morbidity and mortality and are cost-effective; yet they are uncommonly
      prescribed. Supervised exercise training is an accepted intervention in the PAD
      population and has been included in both Canadian and American guidelines for PAD
      management. This review describes (1) key background information related to PAD,
      (2) the initial approach to PAD diagnosis, (3) pharmacologic management options,
      (4) risk-factor modification, and (5) the currently accepted approach to exercise
      training. Key recommendations for enhancing PAD care in a Canadian context are
      also discussed.

PMID- 27692120
TI  - Evaluation of Cardiac, Vascular, and Skeletal Muscle Function With MRI: Novel
      Physiological End Points in Cardiac Rehabilitation Research.
AB  - Impaired exercise tolerance is a major determinant of decreased quality of life
      and survival in individuals with cardiovascular disease. The relative
      contribution that abnormal cardiac, vascular, and skeletal muscle function plays
      in limiting exercise tolerance and its improvement with exercise training in
      patients with cardiovascular disease is not fully known. In this review, we
      provide an overview of the functional impairment of these systems as they relate
      to exercise capacity and the emerging role of magnetic resonance imaging as a
      comprehensive tool to evaluate mechanisms that may explain exercise intolerance.

PMID- 27692121
TI  - Effect of Cardiac Rehabilitation on South Asian Individuals With Cardiovascular
      Disease: Results From the APPROACH Registry.
AB  - BACKGROUND: Unequivocally, cardiac rehabilitation (CR) in patients with
      established cardiovascular disease improves survival. However, its effect on
      higher-risk ethnic groups has not been explored. Accordingly, we evaluated the
      effect of CR on South Asian (SA) compared with European Canadians with coronary
      artery disease (CAD). METHODS: Using the Alberta Provincial Project for Outcome
      Assessment in Coronary Heart Disease (APPROACH) registry, 26,167 patients from
      Edmonton, Alberta who received coronary angiography with documented CAD were
      reviewed (January 2002 to March 2012). After excluding Chinese patients, 1027 SA
      patients were compared with 11,992 European Canadian patients using validated
      surname algorithms. Adjustment was performed using a Cox proportional hazard
      model. RESULTS: Of the SA cohort, 50.6% attended CR, compared with 43.0% of the
      European Canadian cohort (P < 0.001). After adjustment, CR was associated with
      long-term survival irrespective of ethnic group (total study population: hazard
      ratio [HR], 0.57; 95% confidence interval [CI], 0.52-0.63; P < 0.001; SA
      population: HR, 0.63; 95% CI, 0.40-0.99; P = 0.045; European population: HR,
      0.57; 95% CI, 0.52-0.63; P < 0.001). When comparing SA vs European Canadians
      attending CR, improved survival was observed in SA patients (HR, 0.58; 95% CI,
      0.40-0.85; P < 0.001). This benefit appeared limited to SA patients who completed
      CR (complete CR: HR, 0.37; 95% CI, 0.17-0.85; P = 0.02; incomplete CR: HR, 0.78;
      95% CI, 0.45-1.35; P = 0.38). CONCLUSIONS: Overall, referral rates to CR remains
      low but attendance appears higher in SA patients. Among those who attended CR,
      there is a strong association with improved survival irrespective of ethnic
      status. In SA patients with CAD, attendance and completion of CR should be
      strongly endorsed because of its incremental benefit.

PMID- 27692122
TI  - Foreword.

PMID- 27692123
TI  - Comments on the 2016 ESC Guidelines on Cardiovascular Disease Prevention in
      Clinical Practice.

PMID- 27692124
TI  - Effectiveness and Factors Determining the Success of Management Programs for
      Patients With Heart Failure: A Systematic Review and Meta-analysis.
AB  - INTRODUCTION AND OBJECTIVES: Heart failure management programs reduce
      hospitalizations. Some studies also show reduced mortality. The determinants of
      program success are unknown. The aim of the present study was to update our
      understanding of the reductions in mortality and readmissions produced by these
      programs, elucidate their components, and identify the factors determining
      program success. METHODS: Systematic literature review (1990-2014; PubMed,
      EMBASE, CINAHL, Cochrane Library) and manual search of relevant journals. The
      studies were selected by 3 independent reviewers. Methodological quality was
      evaluated in a blinded manner by an external researcher (Jadad scale). These
      results were pooled using random effects models. Heterogeneity was evaluated with
      the I2 statistic, and its explanatory factors were determined using
      metaregression analysis. RESULTS: Of the 3914 studies identified, 66 randomized
      controlled clinical trials were selected (18 countries, 13 535 patients). We
      determined the relative risks to be 0.88 for death (95% confidence interval
      [95%CI], 0.81-0.96; P < .002; I2, 6.1%), 0.92 for all-cause readmissions (95%CI,
      0.86-0.98; P < .011; I2, 58.7%), and 0.80 for heart failure readmissions (95%CI,
      0.71-0.90; P < .0001; I2, 52.7%). Factors associated with program success were
      implementation after 2001, program location outside the United States, greater
      baseline use of angiotensin-converting enzyme inhibitors/angiotensin receptor
      blockers, a higher number of intervention team members and components,
      specialized heart failure cardiologists and nurses, protocol-driven education and
      its assessment, self-monitoring of signs and symptoms, detection of
      deterioration, flexible diuretic regimen, early care-seeking among patients and
      prompt health care response, psychosocial intervention, professional
      coordination, and program duration. CONCLUSIONS: We confirm the reductions in
      mortality and readmissions with heart failure management programs. Their success
      is associated with various structural and intervention variables.

PMID- 27692125
TI  - 2016 European Guidelines on cardiovascular disease prevention in clinical
      practice.

PMID- 27692128
TI  - Step-down treatment from medium-dosage of budesonide/formoterol in controlled
      asthma.
AB  - BACKGROUND: The stepping down of asthma treatment can be considered when asthma
      symptoms have been well controlled with inhaled corticosteroids (ICSs)/long
      acting beta2 adrenergic agonists (LABAs). However, few data are available
      comparing the efficacy between two step-down strategies, to reduce ICS/LABA dose
      or to withdraw LABA continuing ICS, in well-controlled asthmatics. METHODS: This
      was a prospective multicentre randomized, two-arm, controlled study. Ninety-one
      asthmatic patients controlled by budesonide/formoterol combination (BFC) 320/9
      MUg twice daily were assigned to 2 stepping-down treatments as follows: the BFC
      group; BUD/FM 160/4.5 MUg twice daily, and the ICS group; ICS (budesonide 400 MUg
      twice daily or equivalent dose of ICS) without LABA, and followed for 12 weeks.
      The primary outcome was the incidence of asthma exacerbations. Asthma control,
      pulmonary function tests, and fraction of exhaled nitric oxide (FeNO) were
      evaluated at the beginning and end of the period. RESULTS: The incidence of
      exacerbations was 16.3% in the BFC groups and 12.5% in the ICS group, which were
      not different between the groups (p = 0.766). No significant differences were
      found in QOL score and FeNO between 0 week and 12 week in the both group. FEV1
      and FEV1 percentage of the predicted value were lower at week 12 than at week 0
      in the ICS group, but not in the BFC group. CONCLUSIONS: The two step-down
      strategies for 12 weeks have equal acceptability in well-controlled asthmatics
      treated with medium-dose of BFC, however, withdrawal of LABA may have potential
      risk to deteriorate FEV1. CLINICAL TRIAL REGISTRATION: This study was registered
      to UMIN-CTR (http://www.umin.ac.jp/ctr/), UMIN000010333.

PMID- 27692129
TI  - Impact of asthma on mortality in older women: An Australian cohort study of
      10,413 women.
AB  - BACKGROUND: Comorbid conditions frequently coexist with asthma in older adults
      and can alter the natural history of asthma, complicating management and
      affecting overall prognosis and survival. OBJECTIVES: This study investigates the
      impact of asthma on mortality among older women, with a specific interest in
      influence of comorbidities and social factors on survival of older women with
      asthma. DESIGN: Participants were from the Australian Longitudinal Study on
      Women's Health and were born between 1921 and 1926. Cox proportional hazards were
      used to evaluate mortality rates for women with and without asthma, after
      adjustment for comorbidities and other factors. RESULTS: Of 10,413 women aged 73
      78, 829 (8%) reported having been diagnosed by a doctor for asthma. Women with
      asthma had a higher likelihood of heart disease, hypertension, thrombosis,
      bronchitis/emphysema, osteoporosis and major illnesses (p < 0.0001). Asthma was
      associated with increased risk of death (HR = 1.31, 95%CI 1.18-1.45, p < 0.0001).
      After adjusting for age, demographic factors, comorbidities, risk factors,
      residential area and social support, women with asthma retained a 17% increased
      risk of death compared to women without asthma (HR = 1.17, 95%CI 1.03-1.32, p =
      0.016). CONCLUSION: Older women with asthma have a higher rate of mortality
      compared with other women of the same age. This increased risk of death remains
      after age, demographic factors, comorbidities, risk factors, residential area and
      social support have been taken into account.

PMID- 27692130
TI  - Factors associated with pulmonary hypertension and long-term survival in
      bronchiectasis subjects.
AB  - BACKGROUND: The development of pulmonary hypertension (PH) and its effect on long
      term survival in bronchiectasis subjects has not been explored. The present study
      aims to analyze the factors associated with PH and its effect on long-term
      survival in bronchiectasis subjects. METHODS: We prospectively evaluated 23
      bronchiectasis subjects without PH and 16 with PH, as well as 20 healthy
      volunteers. RESULTS: Bronchiectasis subjects with PH were more hypoxemic and had
      a greater number of involved lobes in high resolution computed tomography (HRCT)
      than did the bronchiectasis subjects without PH (P < 0.001 and P < 0.001,
      respectively). At three years, the survival rate was 95.7% for bronchiectasis
      subjects without PH and 56.3% for bronchiectasis with PH, and at 5 years, these
      rates were 95.7% and 62.5%, respectively (P = 0.002). Multivariate Cox regression
      analysis revealed that only the Medical Research Council (MRC) dyspnea score was
      independently related to poor survival in all bronchiectasis subjects (hazard
      ratio: 6.98; 95% CI: 2.41-20.23; P < 0.00001). CONCLUSIONS: Subjects with PH are
      more hypoxemic and have a greater number of involvements in the lobes of the
      lungs. Bronchiectasis subjects with PH have worse survival than do bronchiectasis
      subjects without PH. MRC dyspnea score is an independent predictor of long-term
      survival.

PMID- 27692132
TI  - Ethnic and socio-economic differences in the prevalence of wheeze, severe wheeze,
      asthma, eczema and medication usage at 4 years of age: Findings from the Born in
      Bradford birth cohort.
AB  - BACKGROUND: Asthma, wheeze and eczema are common in early childhood and cause
      considerable morbidity. Generally rates of these conditions are higher in high
      income compared to low income countries. Rates in developed nations are generally
      higher than in less developed countries. After migration to Western countries,
      differences in risks of developing these conditions may between migrant and non
      migrant may diminish. METHODS: A convenience sample of 1648 children of White
      British, Pakistani or Other ethnicity aged between 4 and 5 years were recruited
      from the main Born in Bradford cohort. Children's parents or guardians were asked
      to report on a range of potential risk factors and their associations with
      wheeze, asthma and eczema. Relationships between ethnicity and disease outcomes
      were examined using logistic regression after adjustment for other relevant risk
      factors and confounders. RESULTS: Ethnic differences in doctor diagnosed asthma
      were evident, with children of other ethnic Origin being less likely and children
      of Pakistani origin more likely to have a diagnosis than White British or other
      origin children, although after adjustment for other risk factors this difference
      only remained significant for the Other Ethnic group. Ethnic differences were not
      observed in other outcomes including wheeze in the past 12 months, severe wheeze
      and taking medications for breathing problems. CONCLUSIONS: In UK born children,
      traditional risk factors such as gender, family history, socio-economic status
      and child's medical history may be stronger risk factors than ethnicity or
      familial migration patterns.

PMID- 27692131
TI  - Randomised, double-blind, placebo-controlled, cross-over single dose study of the
      bronchodilator duration of action of combination fluticasone furoate/vilanterol
      inhaler in adult asthma.
AB  - BACKGROUND: Fluticasone furoate (FF)/vilanterol (VI) is a once-daily maintenance
      treatment for asthma and chronic obstructive pulmonary disease. The duration of
      bronchodilation beyond 24 h has not been determined previously. METHODS: Adults
      aged 18-65 (n = 32), with asthma and reversibility to salbutamol (>=15% and >=200
      mL increase in forced expiratory volume in 1 s [FEV1]) participated in a double
      blind, placebo-controlled, crossover study. Patients were admitted to a clinical
      trials unit for 72 h, and inhaled, in random order, placebo or FF/VI 100/25 mcg
      via ELLIPTA dry powder inhaler on two occasions 7-14 days apart. FEV1 was
      measured at baseline, 15 and 30 min, 1, 2, 4, 12, 24, 36, 48, 60, and 72 h. The
      differences in change in FEV1 from baseline between treatments and corresponding
      two-sided 95% confidence intervals (CI) were calculated at each time point.
      FINDINGS: FF/VI produced a rapid onset of bronchodilation (adjusted mean
      difference in change from baseline in FEV1 versus placebo at 15 min, 252 mL [95%
      CI 182-322]). Maximum bronchodilation was observed at 12 h (adjusted mean
      difference in the change from baseline in FEV1, 383 mL [95% CI 285-481]).
      Bronchodilation was maintained throughout the 72-h assessment period (adjusted
      mean difference in the change in FEV1 from baseline at 72 h, 108 mL (95% CI 15
      200]). FF/VI was well tolerated and no serious side effects were reported.
      INTERPRETATION: A single dose of FF/VI 100/25 mcg showed evidence of a 72-h
      bronchodilator duration of action in adults with asthma.

PMID- 27692133
TI  - Characterization of bronchiectasis in the elderly.
AB  - INTRODUCTION: Although bronchiectasis particularly affects people >=65 years of
      age, data describing clinical characteristics of the disease in this population
      are lacking. This study aimed at evaluating bronchiectasis features in older
      adults and elderly, along with their clinical outcomes. METHODS: This was a
      secondary analysis of six European databases of prospectively enrolled adult
      outpatients with bronchiectasis. Bronchiectasis characteristics were compared
      across three study groups: younger adults (18-65 years), older adults (66-75
      years), and elderly (and >=76 years). 3-year mortality was the primary study
      outcome. RESULTS: Among 1258 patients enrolled (median age: 66 years; 42.5%
      males), 50.9% were >=65 years and 19.1 >= 75 years old. Elderly patients were
      more comorbid, had worse quality of life and died more frequently than the
      others. Differences were detected among the three study groups with regard to
      neither the etiology nor the severity of bronchiectasis, nor the prevalence of
      chronic infection with P. aeruginosa. In multivariate regression model, age (OR:
      1.05; p-value: <0.0001), low BMI (OR: 2.63; p-value: 0.02), previous
      hospitalizations (OR: 2.06; p-value: 0.006), and decreasing FEV1 (OR: 1.02; p
      value: 0.001) were independent predictors of 3-year mortality, after adjustment
      for covariates. CONCLUSION: Bronchiectasis does not substantially differ across
      age groups. Poor outcomes in elderly patients with bronchiectasis might be
      directly related to individual's frailty that should be further investigated in
      clinical studies.

PMID- 27692134
TI  - Efficacy of nasal continuous positive airway pressure on patients with OSA with
      erectile dysfunction and low sex hormone levels.
AB  - PURPOSE: This study aimed to test the hypothesis that erectile dysfunction (ED)
      is common in men with obstructive sleep apnea (OSA). We also assessed the
      efficacy of continuous positive airway pressure (CPAP) treatment for ED and sex
      hormone levels in patients with severe OSA and ED. METHODS: A total of 153 OSA
      patients and 60 healthy controls were enrolled in this study. The International
      Index of Erectile Dysfunction-5 (IIEF-5) score was obtained, and blood samples
      were collected for analysis of sex hormones after polysomnography. The IIEF-5
      score, sex hormone levels, and polysomnographic parameters were re-evaluated in
      32 patients with severe OSA and ED after 1 month of CPAP treatment. RESULTS: The
      present study showed that the prevalence of ED was 47.1% in all cases and only
      13.3% in controls, and a lower sex hormone levels was presented in OSA patients.
      OSA patients with ED had greater severity of disease, and lower serum levels of
      follicle stimulating hormone (FSH) and testosterone than OSA patients without ED
      (p < 0.05). After CPAP therapy, there was a significant increase in the IIEF-5
      score, and serum levels of FSH, luteinizing hormone, and testosterone, were
      elevated compared with baseline levels (p < 0.05). Multivariate regression
      analysis indicated the serum level of testosterone had impact on the ED.
      CONCLUSIONS: OSA patients had lower sex hormone levels and a higher occurrence of
      ED than controls, and serum level of testosterone had effect on ED. CPAP
      treatment ameliorated the symptoms of ED and elevated serum levels of FSH,
      luteinizing hormone, and testosterone.

PMID- 27692135
TI  - Evaluation of Chronic Obstructive Pulmonary Disease (COPD) and reduced ejection
      fraction heart failure (HFrEF) discharge medication prescribing: Is drug therapy
      concordant with national guidelines associated with a reduction in 30-day
      readmissions?
AB  - INTRODUCTION: Approximately 1 in 5 hospitalized COPD patients are readmitted
      within 30 days of discharge. CHF coexists in more than 20% of patients with COPD,
      and is associated with early readmission for COPD. Reducing 30-day hospital
      readmissions for COPD is of intense current interest. METHODOLOGY: A
      retrospective chart review was performed to identify patients discharged with
      COPD exacerbation and HFrEF. The primary objective was to evaluate if discharge
      medication prescribing following guidelines for both COPD and HFrEF correlates
      with reduced 30-day readmission rates. RESULTS: The study included 281 admissions
      with 39.1% prescribed appropriate discharge medications for both COPD and HFrEF;
      30-day readmission rate was 24.5% for these patients compared to 31.1% that were
      not prescribed appropriate medications (p = 0.24). Beta blockers, ACE inhibitors
      or ARBS, and aldosterone antagonists were under-prescribed, but this did not
      significantly associate with increased readmission (p = 0.51, p = 0.23 or 0.99,
      and p = 0.18, respectively). Those prescribed hydralazine or nitrates were more
      likely to readmit (both p = 0.01). Diabetes and hyperlipidemia were associated
      with increased readmission (p = 0.01 and 0.05). CONCLUSIONS: This study did not
      show a significant difference in 30-day readmission rate based on appropriate
      discharge medications for both COPD and HFrEF. The comorbidities diabetes and
      hyperlipidemia and prescription of hydralazine or nitrates were significantly
      associated with increased readmission rate. Larger patient populations may be
      needed to assess if guideline based discharge medication prescribing is
      associated with reduced 30-day readmissions for COPD.

PMID- 27692136
TI  - Effects of omalizumab in severe asthmatics across ages: A real life Italian
      experience.
AB  - BACKGROUND: This retrospective study aimed at evaluating long-term effects of
      Omalizumab in elderly asthmatics in a real-life setting. METHODS: 105 consecutive
      severe asthmatics (GINA step 4-5; mean FEV1% predicted:66 +/- 15.7) treated with
      Omalizumab for at least 1 year (treatment mean duration 35.1 +/- 21.7 months)
      were divided into 3 groups according to their age at Omalizumab treatment onset:
      18-39, 40-64 and >= 65 years. RESULTS: Comorbidities, number of overweight/obese
      subjects and patients with late-onset asthma were more frequent among older
      people. A similar reduction of inhaled corticosteroids dosage and SABA on-demand
      therapy was observed in all groups during Omalizumab treatment; a similar FEV1
      increased was also observed. Asthma Control Test (ACT) improved significantly (p
      < 0.001) in the three groups, increasing from 15 [IQR:12-18] to 24 [IQR:22-25] in
      younger subjects, from 14 [IQR:10-16] to 21 [IQR:20-23] in the 40-64-year-group
      and from 15 [IQR:12-16] to 20 [IQR:18-22] in elderly patients where improvement
      was lower (p = 0.039) compared to younger people. Asthma exacerbations decreased
      significantly after Omalizumab but the percentage of exacerbation-free patients
      was higher in younger people (76.9%) compared to middle aged patients (49.2%) and
      the elderly (29%) (p = 0.049). After Omalizumab treatment, the risk for
      exacerbations was lower in subjects aged 40-64 (OR = 0.284 [CI95% = 0.098-0.826],
      p = 0.021) and 18-39 (OR = 0.133 [CI95% = 0.026-0.678], p = 0.015), compared to
      elderly asthmatics. Also, a significantly reduced ACT improvement (beta = -1.070;
      p = 0.046) passing from each age class was observed. CONCLUSION: Omalizumab
      improves all asthma outcomes independently of age, although the magnitude of the
      effects observed in the elderly seems to be lower than in the other age groups.

PMID- 27692138
TI  - Coexistence of asthma and polycystic ovary syndrome: A concise review.
AB  - Asthma may be associated with polycystic ovary syndrome (PCOS), and possibly
      patients with PCOS have a more severe type of asthma. The purpose of this
      systematic literature review is to summarize evidence of a coexistense of PCOS
      and asthma using the available literature. The search was completed on
      01.01.2016. English language articles were retrieved using the search terms
      'Asthma' AND 'PCOS', 'Asthma' AND 'systemic inflammation', 'Asthma' AND
      'metabolic syndrome', 'asthma' AND 'gynaecology', 'PCOS' AND 'systemic
      inflammation', 'PCOS' AND 'metabolic syndrome', 'PCOS' AND 'allergy'. Five papers
      meeting prespecified search criteria were found of which two were registry
      studies of relevance. The current literature supports a coexistense of PCOS and
      asthma and gives us an indication of the causes for the possible link between
      PCOS and asthma. Further research in the area must be conducted to determine the
      exact nature and magnitude of the association.

PMID- 27692137
TI  - Clinical features and natural history of interstitial pneumonia with autoimmune
      features: A single center experience.
AB  - OBJECTIVE: To describe the clinical phenotype and natural history of a cohort of
      patients with interstitial pneumonia with autoimmune features (IPAF). METHODS: A
      retrospective, single center study of 56 patients with IPAF evaluated between
      February 2008 and August 2014. All clinical data were extracted from the
      electronic medical record and longitudinal changes in forced vital capacity (FVC)
      were analyzed with mixed-effects, piecewise linear regression models that
      considered time as a continuous factor. RESULTS: All patients fulfilled
      classification criteria for IPAF. The majority were women (71%) and never smokers
      (68%). The most frequently identified clinical features were Raynaud's phenomenon
      (39%), distal digital fissuring (29%), Gottron's sign (18%) and inflammatory
      arthropathy (16%). The most frequently identified serologies were antinuclear
      antibody (ANA) (48%), anti-Ro (SSA) (43%) and anti-tRNA-synthetase antibodies
      (36%). Nonspecific interstitial pneumonia (NSIP) (57.1%) followed by NSIP with
      organizing pneumonia (18%) were the most common radiologic patterns, while usual
      interstitial pneumonia was identified in only 9%. All but one patient was treated
      with immunosuppression: prednisone (82%) and mycophenolate mofetil (76%) were the
      most frequently used agents. During a follow-up period of 284.9 +/- 141.3 days,
      modeled longitudinal FVC% was stable (slope = 0.69/year) and no deaths were
      observed in the cohort. CONCLUSIONS: In this single center study, patients with
      IPAF were predominately non-smoking women with high-resolution computed
      tomography scans that suggested NSIP. Their pulmonary physiology was stable, and
      during limited follow-up, no deaths were observed. Prospective and multi-center
      studies are needed to better inform our understanding of IPAF.

PMID- 27692139
TI  - Socioeconomic inequalities in adherence to inhaled maintenance medications and
      clinical prognosis of COPD.
AB  - BACKGROUND: Low socioeconomic status has been associated with adverse outcomes in
      chronic obstructive pulmonary disease (COPD), but population-based data are
      sparse. We examined the impact of education, employment, income, ethnicity, and
      cohabitation on the risk of suboptimal adherence to inhaled medication,
      exacerbations, acute admissions, and mortality among COPD patients. METHODS:
      Using nationwide healthcare registry data we identified 13,369 incident hospital
      clinic outpatients with COPD during 2008-2012. We estimated medication adherence
      as proportion of days covered (PDC) one year from first contact. With Poisson
      regression we computed adjusted relative risks (aRR) of poor adherence and non
      use. With Cox regression we calculated adjusted hazard ratios (aHR) of clinical
      outcomes. RESULTS: 32% were poor adherers (PDC<0.8) and 5% non-users (PDC = 0).
      Analyses showed a higher risk of poor adherence among unemployed (aRR1.36, 95% CI
      1.20-1.54), low income patients (aRR = 1.07, 95% CI 1.00-1.16), immigrants (aRR =
      1.29, 95% CI 1.17-1.44), and patients living alone (aRR = 1.17, 95% CI 1.11
      1.24). Similarly, non-use was associated with unemployment (aRR = 2.75, 95% CI
      2.09-3.62), low income (aRR = 1.37, 95% CI 1.10-1.70), immigrant status (aRR =
      1.56, 95% CI 1.17-2.08), and living alone (aRR = 1.53, 95% CI 1.30-1.81). Low
      education was associated with exacerbations (aHR = 1.21, 95% CI 1.10-1.35) and
      admissions (aHR = 1.22, 95% CI 1.07-1.38). Low income was associated with
      admissions (aHR = 1.20, 95% CI 1.09-1.32), and death (aHR = 1.11, 95% CI 0.99
      1.25). The unemployed and those living alone had lower exacerbation-risk but
      higher mortality-risk. CONCLUSIONS: In Denmark, health equity is a stated
      priority in a public health care system. Nevertheless, there are substantial
      socioeconomic inequalities in COPD treatment and outcomes.

PMID- 27692140
TI  - Bronchoalveolar lavage for the diagnosis of Pulmonary Langerhans cell
      histiocytosis.
AB  - BACKGROUND: The histologic diagnosis of Pulmonary Langerhans cell histiocytosis
      (PLCH) is invasive and can cause complications. To confirm the diagnosis of PLCH,
      guidelines therefore recommend measuring CD1a-positive bronchoalveolar lavage
      fluid (BALF) cells despite its poor sensitivity and specificity. Thus, an
      improved diagnostic accuracy of BALF cell analysis would be desirable. METHODS:
      Using four-colour flow cytometry, plasmacytoid and myeloid dendritic cells (DCs)
      were analysed in BALF of 10 newly diagnosed, untreated, smoking patients with
      PLCH, and compared with BALF DCs from 40 asymptomatic smokers and 21 never
      smokers. RESULTS: Compared with controls, myeloid DCs (median: 0.79% of BALF
      leukocytes) and their subpopulation of Langerhans cells (median: 0.44% of BALF
      leukocytes) were not increased in PLCH. Patients with PLCH displayed a normal
      expression of the maturity marker CD83 on BALF myeloid DCs. However, the
      expression of the co-signaling molecule CD80 on BALF myeloid DCs was
      significantly lower than in both control groups, with the lowest expression found
      in more severe disease (presence of cysts > 2 cm in diameter). Based on receiver
      operating characteristic (ROC) curve analysis, a cut-off of 53% CD80-positive
      BALF myeloid DCs was optimal for the diagnosis of PLCH, yielding a sensitivity of
      0.90 and a specificity of 0.90. CONCLUSIONS: BALF Langerhans cells are not
      increased in PLCH. However, PLCH is characterised by a low expression of CD80 on
      BALF myeloid DCs. Due to its considerably higher sensitivity and specificity,
      this marker appears to be more appropriate to diagnose PLCH than the currently
      recommended marker CD1a.

PMID- 27692141
TI  - Hepatoid adenocarcinoma of the lung: Review of a rare form of lung cancer.
AB  - RATIONALE: Hepatoid adenocarcinoma (HAC) is a rare malignant lung tumor that
      histologically resembles typical hepatocellular carcinoma (HCC) when it is
      metastatic to the lung. To date, this clinical entity has not been highlighted in
      the pulmonary literature. OBJECTIVE: We present a review of all known cases of
      HAC, including the relevant clinical and histopathological features important for
      pulmonologists. MEASUREMENTS AND MAIN RESULTS: The purpose of this report is to
      present a new case of HAC, with typical clinical and histologic features of this
      malignancy, and to summarize findings of previously reported cases. A systematic
      literature search of the electronic database PUBMED was conducted to identify all
      cases of hepatoid adenocarcinoma reported in the English literature, between
      January 1980 and June 2015. HAC and HCC can be distinguished by
      immunohistochemical staining. HAC usually presents as a large bulky solitary mass
      in the upper lobe; there is an exceedingly high prevalence in males and most
      patients with this tumor are smokers. Serum alpha-fetoprotein (AFP) in very high
      levels has been a distinguishing feature of this tumor. Nodal and distant
      metastases are common at initial presentation and, as a result, the prognosis is
      very poor. Resection and long-term survival, however, have been reported.
      CONCLUSION: Hepatoid adenocarcinoma, first described as a gastric tumor, has also
      been described in the lung. It morphologically resembles and must be
      distinguished from metastatic HCC of the lung. While most tumors produce AFP, the
      case we present demonstrates that this should not be a criterion for diagnosis.

PMID- 27692142
TI  - Tuberculosis. Digging deep in the soul of humanity.
AB  - Tuberculosis (TB) is one of the oldest infectious diseases that affected
      humankind. A quintessential social disease, TB remains one of the world's
      deadliest communicable diseases, with still a high mortality and burden of
      disease. Social representations of TB focus on aspects associated to feelings and
      manifestations awakened by the disease, sometimes reinforcing stigmas and
      prejudices about the way of perceiving TB. TB is a historic disease now reborn
      with a deeper social stigma. Despite the modest reduction in TB incidence
      worldwide, its incidence is still rising in certain crisis-affected populations
      like refugees, and in those bearing high prevalence of HIV, persisting poverty,
      especially in the developing world. Fear and stigma may appear justified with the
      increasing rates of multi-drug resistant (MDR) TB, and now extremely drug
      resistant (XDR) TB. However, stigmatization of TB poses serious obstacles to
      current TB control efforts, as socio-cultural aspects can influence adherence to
      TB treatment.

PMID- 27692143
TI  - Molecular mechanisms underlying hyperoxia acute lung injury.
AB  - The management of acute hypoxemic respiratory failure frequently includes the use
      of supraphysiological fractions of inspired oxygen (FiO2), which can be
      beneficial in the short-term but not without risks in the long-term, causing
      acute lung injury (ALI). Over the last few years, much attention has been devoted
      to the intracellular signaling transduction pathways that lead to hyperoxia
      induced cell damage, particularly MAP kinase cascades. Identification of involved
      signaling molecules and understanding of the regulation of the main signal
      transduction pathways might provide the basis for improving the outcome of
      patients under high FiO2 exposure through more effective therapeutic
      interventions. This review, which includes studies published from 1987 to 2015,
      presents an overview on recent progresses in the hyperoxia ALI field with special
      emphasis on potential therapeutic targets and clinical approaches based on the
      molecular mechanisms underlying hyperoxia-induced inflammation. Further studies
      are needed to gain deeper insight into controversial molecular mechanisms
      underlying hyperoxia-induced cell death, which may play a critical role in future
      pharmacological interventions, as well as into hyperoxia-induced cell damage,
      that could monitor and therefore prevent hyperoxia ALI.

PMID- 27692145
TI  - The relationship of body habitus and respiratory function in Duchenne muscular
      dystrophy.
AB  - BACKGROUND: The multidisciplinary care of Duchenne muscular dystrophy (DMD)
      incorporates management of nutrition and the respiratory system, however the
      effect of body habitus on respiratory function in DMD is poorly understood. The
      present study examined the impact of nutritional status on respiratory function
      in DMD to guide further treatment strategies. METHODS: Anthropometric and
      respiratory parameters, such as body mass index (BMI) z-scores, forced vital
      capacity (FVC) and forced expiratory volume in one second (FEV1) were
      retrospectively analysed with a mixed linear model in 34 DMD patients. Cross
      sectional analysis of cough peak flow (CPF) in upright and supine positions and
      body fat mass were examined in 12 DMD patients. RESULTS: Respiratory function in
      DMD patients was significantly related to BMI Z-score (P < 0.001), age (P < 0.05)
      and mobility (P < 0.001). DMD patients with greater BMI Z-score had increased
      respiratory function, even when adjusting for age and mobility status, with a 1
      unit increase in BMI z-score associated with a 7.43% increase in FVC% predicted
      (P < 0.001). Body fat mass was adversely associated with FVC with a 1% body fat
      increase associated with a 1.5% reduction in FVC (P < 0.05). CPF values were
      significantly lower in supine compared to upright position (P = 0.005) and
      greater postural reductions in CPF were associated with higher body fat percent,
      with a 1% body fat increase associated with a 1.5% increase in postural CPF
      difference (P < 0.05). CONCLUSION: The present study reinforces the importance of
      weight management in DMD, showing that a higher weight profile and lower
      adiposity have better respiratory outcomes. Furthermore, attention to body
      position with airway clearance techniques will maximize their effectiveness.

PMID- 27692144
TI  - Bronchodilator response in wheezing infants assessed by the raised volume rapid
      thoracic compression technique.
AB  - BACKGROUND: Bronchodilator response (BDR) analyzed by the raised volume rapid
      thoracic compression (RVRTC) in wheezing infants is not yet well described,
      although bronchodilators (BD) are routine in the treatment of this population.
      OBJECTIVE: To evaluate BDR by RVRTC technique in infants with recurrent wheezing
      and compare to control group. METHOD: Cross sectional study, 45 infants, age 56
      weeks (38-67 weeks). Two groups: wheezing group (WG: history of recurrent
      wheezing) and control group (CG). RVRTC was evaluated, FVC, FEV0.5, FEF50, FEF75,
      FEF85, FEF25-75 were measured. Salbutamol was delivered to infants and RVRTC
      evaluated again. BDR was determined by the increase greater than two standard
      deviation from the mean change in the CG. RESULTS: In WG (n = 32) lung function
      was worse than in CG (n = 13): FEV0.5: 0.0(-0.9-0.9z score) vs 0.8(0.2-1.4z
      score); FEF50: 0.2(-0.3-1.1z score) vs 0.9(0.5-1.4z score); and FEF25-75: 0.2(
      0.5-1.1z score) vs 1.1(0.6-1.6z score), respectively, p < 0.05. Both groups had
      similar increase after BD. In WG 11 patients (34%) were responder and these had
      worse lung function compared to nonresponder (n = 21) (p < 0.05). The increase in
      lung function after BD in responder was higher than in nonresponder: FEV0.5:
      6.5(2.1-7.1%) vs -0.5(-2.5-0.7%), FEF50: 5.1(2.7-11.7%) vs 0.4(-1.1-2.8%), FEF75:
      20.7(4.7-23.6%) vs -1.3(-6.4-3.9%), FEF25-75: 9.9(3.8-16.4%) vs 0.0(-1.5-1.0%),
      respectively, p < 0.05. CONCLUSION: 34% WG showed BDR measured by the RVRTC. The
      best variables to detect BDR were FEF75, FEF25-75 and FEV0.5. Patients with worse
      lung function showed better response to BD.

PMID- 27692147
TI  - Real life data on incidence and risk factors of severe asthma exacerbations in
      children in primary care.
AB  - Real-life data on the incidence rates (IR) and risk factors of severe asthma
      exacerbations in children are sparse. We aimed to assess IR and risk factors of
      severe asthma exacerbations in children in real life. We conducted a population
      based cohort study using a Dutch GP database containing complete medical records
      of >1 million patients. All records of children with physician-diagnosed asthma
      aged 5-18 years between 2000 and 2012 were examined for exacerbations, defined as
      either hospitalization, emergency department visit or need of systemic steroids
      for asthma. IR was expressed as number of exacerbations per person year (PY). We
      identified 14,303 asthmatic children with 35,118 PY of follow-up and 732
      exacerbations. The overall IR was 2.1/100PY (95% CI 1.9-2.2), 4.1/100PY (3.8-4.4)
      for children on asthma treatment. Re-exacerbation occurred in 2% (1.3-4.3) of
      patients within 1 month, in 25% (20.6-28.8) within 1 year. Predictors for
      (frequent) exacerbations were age, medication use and prior exacerbations (all p
      < 0.001). The overall IR of severe asthma exacerbations was 4/100PY in children
      on asthma treatment, highest in spring and fall. 25% of the patients with an
      exacerbation will experience a next exacerbation within 1 year. More severe
      asthma is a predictor of subsequent and future exacerbations.

PMID- 27692146
TI  - Primary ciliary dyskinesia in Israel: Prevalence, clinical features, current
      diagnosis and management practices.
AB  - BACKGROUND: Primary Ciliary Dyskinesia (PCD) is rare and its features in Israel
      have not been described. AIMS: to assess prevalence utilizing state-of-the-art
      diagnostic techniques, and describe clinical features, diagnostic and management
      practices in Israel. METHODS: A national multicenter study from 2012 to 2013
      recruited patients diagnosed or suspected of having PCD. Diagnosis was verified
      using: nasal Nitric Oxide (nNO); High-speed Video Microscope Analysis (HVMA);
      Transmission Electron Microscopy (TEM) of cilia; Immuno-fluorescence staining
      (IF) for ciliary proteins, and genetic analysis. RESULTS: Of the 203 patients
      recruited from 14 pediatric centers, 150 had a PCD diagnosis verified. Median age
      was 15.05y, with range 0.15-60.5y. PCD prevalence was 1:54,000 for the general
      population and 1:25,000 in children (5-14 y). For the non-Jewish (mainly Druze
      and Arab Moslem) compared to Jewish populations, prevalence was 1:16,500 and
      1:139,000 respectively (p < 0.0001) and parental consanguinity was 85.4% and
      21.9% respectively (p < 0.0001). Clinical features included bronchiectasis (88%),
      rhinitis (81%), recurrent pneumonia (78%), recurrent otitis (62%), neonatal
      pneumonia (60%) and situs inversus (42%). Prior diagnostic practices varied
      widely between centers with TEM assessed in 55% and abnormal in 61% of these.
      Management included antibiotics and airway clearance. Diagnostic verification
      revealed for 150 PCD patients: 81% nNO<233 ppb, 62% abnormal HVMA, 51% diagnostic
      TEM, 58% diagnostic IF and, 57% genetic diagnosis. CONCLUSIONS: PCD in Israel is
      rare, with comprehensive diagnostic tests showing prevalence in children similar
      to Europe. Prevalence was higher in non-Jews, associated with parental
      consanguinity. Diagnostic and management practices vary. Referral centers
      providing comprehensive diagnostic and care capabilities should be established.

PMID- 27692148
TI  - A pilot study to monitor changes in spirometry and lung volume, following an
      exacerbation of Chronic Obstructive Pulmonary Disease (COPD), as part of a
      supported discharge program.
AB  - BACKGROUND: One-third of patients with an exacerbation of Chronic Obstructive
      Pulmonary Disease(COPD) are re-hospitalised at 90 days. Exacerbation recovery is
      associated with reductions in lung hyperinflation and improvements in symptoms
      and physical activity. We assessed the feasibility of monitoring these clinical
      parameters in the home. We hypothesised that the degree of change in spirometry
      and lung volumes differs between those who had an uneventful recovery and those
      who experienced a further exacerbation. METHODS: Hospitalised patients with an
      acute exacerbation of COPD referred for a supported discharge program
      participated in the study. Spirometry and Inspiratory Vital Capacity(IVC) were
      measured in the home at Days 1, 14 and 42 post-discharge. Patients also completed
      Medical Research Council(MRC), Borg and COPD Assessment Test(CAT) scores and were
      provided with a tri-axial accelerometer. Any new exacerbation events were
      recorded. RESULTS: Sixty-five patients with 72 exacerbation episodes were
      recruited. Fifty percent experienced a second exacerbation. Adequate IVC
      measurements were achieved by 90%, while only 70% completed spirometry.
      Uneventful recovery was accompanied by significant improvements in physiological
      measurements at day14, improved symptom scores and step count, p < 0.05. Failure
      of MRC to improve was predictive of re-exacerbation(Area Under Receiver Operating
      Curve(AUROC) 0.6713) with improvements in FEV1>=100 ml(AUROC 0.6613) and mean
      daily step count >=396 steps(AUROC 0.6381) predictive of recovery. CONCLUSION:
      Monitoring the pattern of improvement in spirometry, lung volumes, symptoms and
      step count following a COPD exacerbation may help to identify patients at risk of
      re-exacerbation. It is feasible to carry out these assessments in the home as
      part of a supported discharge programme.

PMID- 27692149
TI  - Physiological responses during exercise with video games in patients with cystic
      fibrosis: A systematic review.
AB  - BACKGROUND: Interactive video games are recently being used as an exercise tool
      in cystic fibrosis (CF). This study aimed to assess the literature describing
      whether video games generate a physiological response similar to the exercise
      intensity needed for training in CF. METHODS: An online search in PubMed, Embase,
      Cochrane, SciELO, LILACS and PEDro databases was conducted and original studies
      describing physiological responses of the use of video games as exercise in CF
      were included. RESULTS: In four, out of five studies, the heart rate achieved
      during video games was within the standards recommended for training (60-80%).
      Two studies assessed VO2 and showed higher levels compared to the six-minute walk
      test. No desaturation was reported. Most games were classified as moderate
      intensity. Only one study used a maximum exercise test as comparator. CONCLUSION:
      Interactive video games generate a heart rate response similar to the intensity
      required for training in CF patients.

PMID- 27692150
TI  - Respiratory drugs and macrolides prevent asthma exacerbations: A real-world
      investigation.
AB  - OBJECTIVE: We investigated the real-world effectiveness of several drugs
      (including short- and long-acting beta-agonists [SABAs and LABAs], inhaled
      corticosteroids [ICS], and antibiotics) in preventing severe asthma exacerbations
      by carrying-out a large observational study based on the healthcare utilization
      databases of the Italian Lombardy Region. METHODS: We identified all patients
      aged 6-40 years who performed an Emergency Department visit for asthma during
      2010-2012 as cases. To address bias due to unmeasured confounders, we implemented
      a case-crossover (CC) design. Addressing other specific sources of systematic
      errors (e.g. protopathic bias) was of particular concern in this study. RESULTS:
      A total of 7300 cases were included in the study. The CC odds ratios (95%
      confidence intervals) for current vs. past use were 0.81 (0.71, 0.92) for SABAs,
      0.83 (0.72, 0.96) for ICS, 0.78 (0.66, 0.91) for LABA/ICS fixed combinations,
      0.79 (0.65, 0.97) for other respiratory drugs, and 0.79 (0.69, 0.92) for
      macrolides antibiotics. Sensitivity analyses showed that our results were robust
      with respect to several sources of bias. CONCLUSIONS: Our study provides evidence
      from the real-world clinical practice on the effectiveness of several respiratory
      drugs and macrolides in reducing the risk of severe asthma exacerbations.

PMID- 27692151
TI  - Computed tomography (CT)-assessed bronchodilation induced by inhaled indacaterol
      and glycopyrronium/indacaterol in COPD.
AB  - BACKGROUND: Our previous studies suggested that the site of bronchodilation on CT
      might differ between inhaled beta2 agonists and inhaled anticholinergics in COPD.
      AIM: To assess and compare the bronchodilation effects of inhaled indacaterol and
      glycopyrronium/indacaterol by airway generation in large airways using CT.
      METHODS: CT scans at full inspiration and pulmonary function tests were done in
      25 patients with moderate-severe COPD before and 4-5 weeks after daily inhalation
      of indacaterol and again another 4-5 weeks after inhalation of
      glycopyrronium/indacaterol. Airway inner luminal area (Ai) at the 3rd (segmental)
      to 6th generation of 8 selected bronchi, a total of 32 sites, in the right lung
      was analyzed on 3 occasions. Our proprietary software enables us to select the
      same airways and the same measurement sites for comparison, with simultaneous
      confirmation using two screens on the computer. RESULTS: The overall increase of
      Ai (DeltaAi, %) averaged at all 32 measurement sites induced by
      glycopyrronium/indacaterol had a significant correlation with FEV1 improvement (r
      = 0.7466, p < 0.0001). Both DeltaAi, % with indacaterol and DeltaAi, % with
      additional glycopyrronium were significant at the 3rd to 6th generations.
      Remarkable increases in DeltaAi, % were found at the 5th and 6th generations in
      several subjects with indacaterol or additional glycopyrronium. There were no
      significant site-differences in the bronchodilation pattern caused by indacaterol
      and by glycopyrronium/indacaterol at any of the 3rd to 6th generations.
      CONCLUSIONS: Additional bronchodilation with glycopyrronium was demonstrated by
      CT at the 3rd to 6th generations, with no site-specific differences in
      bronchodilation between indacaterol and glycopyrronium/indacaterol. This study
      was registered in the UMIN Clinical Trials Registry (UMIN-CTR) system
      (http://www.umin.ac.jp/. ID. UMIN000012043).

PMID- 27692152
TI  - Respiratory pattern in a FSHD pediatric population.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant inherited
      disorder characterized by selective weakness of face and upper arms and girdle.
      Respiratory involvement in FSHD has been described mainly in the most severely
      affected patients. In this work we tested the respiratory function by spirometry
      in 12 patients affected by FSHD with onset before 18 years. Spirometry results
      were correlated with motor involvement and compared to aged matched group of
      Becker patients. Of note FSHD patients present a peculiar pattern characterized
      by a flat shape in flow-volume loop. Respiratory volumes correlate with clinical
      severity and expiratory phase is specifically affected in comparison to other
      muscular dystrophies.

PMID- 27692153
TI  - Diastolic pulmonary gradient predicts outcomes in group 1 pulmonary hypertension
      (analysis of the NIH primary pulmonary hypertension registry).
AB  - BACKGROUND: Diastolic pulmonary gradient (DPG), calculated as the difference
      between pulmonary artery diastolic pressure and mean pulmonary capillary wedge
      pressure >= 7 mmHg is associated with pulmonary vascular disease and portends
      poor prognosis in heart failure (HF). The prognostic relevance of DPG in group 1
      pulmonary hypertension (PH) is uncertain. METHODS: Using the Pulmonary
      Hypertension Connection (PHC) risk equation for 225 patients in the NIH-PPH, the
      5-year probability of death was calculated, which was then compared with DPG
      using a Cox proportional hazards model. Kaplan-Meier survival curves were
      determined for two cohorts using the median DPG of 30 mmHg as cutoff, and
      significance was tested using the log-rank test. RESULTS: The mean age was 38.1
      +/- 16.0 years old, 63% female, and 72% were "white". The mean DPG was 31.6 mmHg
      +/- 13.8 mm Hg and only 1.8% had a DPG <7 mm Hg. Increasing DPG was significantly
      associated with increased 5-year mortality even after adjustment for the PHC risk
      equation (HR 1.29 per 10 mm Hg increase). When DPG was dichotomized based on the
      median of 30 mm Hg, the HR for DPG >30 mm Hg with respect to 5-year mortality was
      2.03. After adjustment for pulmonary artery systolic pressure (PASP), increasing
      DPG remained significantly associated with decreased 5 years survival (HR 1.99
      for DPG > 30 mm Hg). CONCLUSIONS: DPG is independently associated with survival
      in group 1 PH patients even after adjustment for the PHC risk equation or PASP.
      Patients with increased DPG had a 2-fold increased risk of mortality. The use of
      DPG for guiding treatment and prognosis in group 1 PH should be further
      investigated.

PMID- 27692154
TI  - Determinants of exercise-induced oxygen desaturation including pulmonary
      emphysema in COPD: Results from the ECLIPSE study.
AB  - Exercise-induced oxygen desaturation (EID) is related to mortality in patients
      with chronic obstructive pulmonary disease (COPD). We investigated: (1) the
      prevalence of EID; (2) the relative-weight of several physiological determinants
      of EID including pulmonary emphysema, and (3) the relationship of EID with
      certain patients' clinical characteristics. Data from 2050 COPD patients (age:
      63.3 +/- 7.1years; FEV1: 48.7 +/- 15.7%pred.) were analyzed. The occurrence of
      EID (SpO2post <=88%) at the six-minute walking test (6MWT) was investigated in
      association with emphysema quantified by computed-tomography (QCT), and several
      clinical characteristics. 435 patients (21%) exhibited EID. Subjects with EID had
      more QCT-emphysema, lower exercise capacity and worse health-status (BODE, ADO
      indexes) compared to non-EID. Determinant of EID were obesity (BMI>=30 kg/m2),
      impaired FEV1 (<=44%pred.), moderate or worse emphysema, and low SpO2 at rest
      (<=93%). Linear regression indicated that each 1-point increase on the ADO-score
      independently elevates odds ratio (<=1.5fold) for EID. About one in five COPD
      patients in the ECLIPSE cohort present EID. Advanced emphysema is associated with
      EID. In addition, obesity, severe airflow limitation, and low resting oxygen
      saturation increase the risk for EID. Patients with EID in GOLD stage II have
      higher odds to have moderate or worse emphysema compared those with EID in GOLD
      stage III-IV. Emphysematous patients with high ADO-score should be monitored for
      EID.

PMID- 27692155
TI  - Clinical characteristics in patients with asymmetric idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: A group of patients with idiopathic pulmonary fibrosis (IPF) presents
      with disease affecting one lung markedly more than the other. At this time, it is
      unclear how this population differs from those who present with more symmetric
      disease. We sought to explain the characteristics of the asymmetric group and how
      their disease progresses. METHODS: In this retrospective case-control study we
      accessed an interstitial lung disease (ILD) database and identified 14 asymmetric
      IPF cases via high-resolution computed tomography (HRCT) scoring of each lung
      lobe's disease severity. We identified 28 symmetric IPF controls from the same
      database using the same methods, and compared the clinical features of each
      group. RESULTS: Patients with asymmetric disease exhibited similar demographics
      as those in the general IPF population; they were predominantly male (64%),
      elderly (69 years old), and used tobacco (57%). We found a trend toward
      significantly increased all-cause mortality in the case population two years
      following diagnosis (p = 0.089). Pulmonary function tests were significantly
      lower in the case group at the time of diagnosis, then both groups experienced
      gradual decline. We found no statistically significant differences in number of
      IPF exacerbations (cases 43%, controls 39%, p = 0.824) and gastro-esophageal
      reflux (both groups 50%). CONCLUSION: Patients with asymmetric IPF resemble
      patients in the general IPF population but may have a lower overall survival
      rate. Further systemic factors may be studied to identify reasons for disease
      asymmetry and clinical decline in this population.

PMID- 27692156
TI  - Hypothesis: Irisin is a metabolic trigger for the activation of the neurohormonal
      axis governing puberty onset.
AB  - A large body of data suggests that body weight influences puberty onset and adult
      reproduction. However, the underlying mechanism of how body weight influences
      puberty onset and fertility is not completely understood. The hypothalamic
      neuronal circuit regulating reproduction is restrained by inhibitory signals
      during childhood. At the time of puberty, these inhibitory signals are weakened
      and supplanted by stimulatory signals that, in turn, stimulate the release of
      gonadotropin-releasing hormone (GnRH) - a hypothalamic neuropeptide governing
      reproduction. A number of studies, however, suggest that puberty commencement
      occurs when body (fat) weight reaches a certain threshold, which is critical for
      the initiation of puberty and for support of the adult reproductive function.
      Previously, various signals have been studied which might link body (fat) weight
      related information to the hypothalamic neuronal network regulating reproduction.
      However, the nature of the signal(s) that may link body fat and/or muscle mass
      with the hypothalamic neuronal network governing reproduction is still unclear.
      It has been intuitively speculated that augmentation of such signal(s) will cause
      a restriction of inhibitory input and activation of stimulatory input to GnRH
      secreting neurons at the time of puberty onset. Therefore, the unveiling of such
      signal(s) will greatly help in understanding the mechanism of puberty onset.
      Recently, it has been shown that expression of fibronectin type III domain
      containing-5 (FNDC5) mRNA in central and peripheral tissues upsurges during
      postnatal development, especially around the time of puberty onset. Moreover, the
      systemic level of irisin - one of the protein products of the FNDC5 gene that is
      secreted as myokine and adipokine - also rises during postnatal development and
      correlates with the timing of puberty onset. Therefore, we propose here that
      irisin might serve as a possible signal for linking body fat/muscle mass with the
      hypothalamic center governing reproductive function. We hypothesize that irisin
      acts as a trigger for the activation of the hypothalamic neuronal network
      monitoring the onset of puberty.

PMID- 27692157
TI  - Connecting the obesity and the narcissism epidemics.
AB  - Obesity and metabolic syndromes are major threats to health in both developed and
      developing countries. This opinion article is a holistic attempt to understand
      the obesity epidemic, by connecting it to the widespread narcissism in society.
      The narcissism epidemic refers to an increased prevalence of status-striving
      individualism and a decreased sense of community, observed in Westerns
      populations and spreading worldwide. Based on social personality and evolutionary
      psychology approaches, I speculate that this rise of narcissism underlies a steep
      social hierarchy resulting in increase of social stress. This social stress
      markedly affects individuals who are sensitive to social hierarchy dominance due
      to their personality, yet are relegated at a lower social position. I speculate
      that over-eating is one major mechanism for coping with this stress, and discuss
      the possibility that visceral fat may constitute an adaptive behaviour to the
      lower social hierarchy position, which is perceived as unjust. Connecting the
      prevalence of obesity to the narcissism epidemic allows for a more thorough
      examination of factors, which contribute to obesity, which includes early
      difficult childhood experience, lower rank, and the overall competitive framework
      of the society.

PMID- 27692159
TI  - Could tea polyphenols be beneficial for preventing the precocious puberty?
AB  - Precocious puberty which impacts children physically and psychologically has
      become one of the health problem over the world. However, the mechanism and
      preventive measures of precocious puberty is still not clear. Recent studies
      suggested that leptin may act as the 'permissive factor' to initiate the puberty
      by regulating gonadotrophin-releasing hormone secretion. Previous evidence from
      animal and human studies found that tea polyphenols can reduce serum leptin
      levels in vivo and inhibit the expression of leptin in adipose tissue. This
      article focus on whether tea polyphenols could delay the onset of puberty by
      reducing leptin levels. To verify the possibility of tea polyphenols on
      preventing precocious puberty, animal experiment can be used. Our hypothesis that
      tea polyphenols could prevent the precocious puberty may provide important
      potential way for the prevention and control of children precocious puberty.

PMID- 27692158
TI  - Soluble adhesion molecules in patients with acute coronary syndrome after
      percutaneous coronary intervention with drug-coated balloon, drug-eluting stent
      or bare metal stent.
AB  - Adhesion molecules play an important role in inflammation, atherosclerosis and
      coronary artery disease (CAD). These molecules are expressed on the surface of
      dysfunctional endothelial cells, causing inflammatory cells from the circulation
      to adhere and migrate through the endothelium. Their expression is upregulated in
      acute coronary syndrome (ACS) and after percutaneous coronary intervention (PCI).
      The contact between stent struts and endothelium upregulates endothelial cell
      gene expression, endothelial cell activation and inflammation. The paclitaxel or
      sirolimus eluting stents inhibited expression of adhesion molecules in several
      studies and reduced the incidence of major adverse cardiac events (MACE) after
      drug-eluting stent (DES) over bare metal stent (BMS) implantation. Therefore, we
      propose that elevated serum levels of the soluble adhesion molecules after
      primary PCI in patients treated with BMS or DES implantation versus drug-coated
      balloon (DCB) application to the vulnerable coronary plaque might be a predictor
      of MACE and further adverse outcomes. Consequently, DCB-only strategy in patients
      with ACS might be a superior approach in comparison to BMS implantation and non
      inferior approach when compared to DES implantation.

PMID- 27692160
TI  - DCoH: A novel biomarker for diagnosing acute kidney injury.
AB  - Initial diagnosis of acute kidney injury (AKI) is usually based on measuring
      serum-creatinine and blood urea nitrogen levels; however such measurements are
      still poor in identifying renal injuries at initial stages. These standard
      matrices are not enough to monitor the outcome and progression of AKI. The
      prognosis prevents proper treatment and timely delay in providing putative
      therapeutic agents. The cost effective therapies to get delayed, patient health
      gets compromised and ultimately requires renal transplant due to end-stage renal
      disease, which is another major problematic factor due to shortage kidney donors.
      To establish effective therapies for AKI the need will be facilitated by
      developing and identifying reliable, sensitive biomarkers which can be detected
      early during all stages of AKI, even during preclinical and clinical studies.
      Although reaching to human clinical trials takes years of thorough evaluations,
      preliminary studies should be carried out effectively by: (a) Employing cell
      culture analysis, (b) use of AKI animal models, studying various gene regulated
      networks, and biomarkers, and (c) patient serum sampling and testing. As elevated
      phenylalanine are indicative of AKI onset within 4h, its levels is controlled, 4a
      Hydroxy-tetrahydrobiopterin dehydratase/dimerization cofactor of HNF-1 (DCoH).
      There is a possibility of targeting DCoH to the current bedside list of
      biomarkers involved in AKI onset.

PMID- 27692161
TI  - A novel treatment for "morning sickness": Nausea of pregnancy could be induced by
      excess sulfite which molybdenum can help alleviate.
AB  - Nausea and vomiting of pregnancy (NVP) remains difficult to treat. Last century,
      thalidomide was used to alleviate NVP, but it caused teratogenesis by interfering
      with angiogenesis. The gasotransmitters hydrogen sulfide (H2S) and nitric oxide
      are mutually dependent on each other for their angiogenesis-related functions.
      Pregnancy-related requirements for increased endogenous H2S could create a
      temporary excess of sulfite, an H2S catabolite, which is toxic and can induce
      nausea. Sulfite oxidase, a molybdenum-containing enzyme, catalyzes oxidation of
      sulfite to sulfate, which can then be excreted or reused by the body.
      Supplementation with molybdenum should facilitate enhanced sulfite oxidase
      activity, thus lowering gestationally-elevated sulfite levels in the
      gastrointestinal tract and easing NVP.

PMID- 27692162
TI  - Colchicine to decrease inflammation and fibrosis in patients with metabolic
      dysregulation.

PMID- 27692163
TI  - Myeloid derived suppressor cell: A new player in periodontal disease?
AB  - Periodontal disease can be initiated by a shift from a symbiotic to a dysbiotic
      microbial community. An increase in the recruitment of leukocytes and production
      of inflammatory cytokines, chemokines and oxidative stress are generated by this
      shift. In periodontitis, an exacerbated, poorly specific and effective
      inflammatory response is mounted. Moreover, failure in the inflammation resolving
      mechanism leads to establishment of a chronic inflammatory process, resulting in
      the progressive destruction of bone and soft tissue. In different diseases
      presenting chronic inflammation some important players of immune response are
      defectives. Thus, an immunosuppressive environment could be induced during
      chronic inflammation. Myeloid derived suppressor cells (MDSC), a heterogenic
      group of immature myeloid cells with potent immune suppressive activity, are
      increased in several acute and chronic inflammatory diseases. Dysbiosis-mediated
      inflammation can induce increased frequency of MDSC. In addition, mediators
      generated in diverse inflammatory diseases have demonstrated to promote
      expansion, activation and recruitment of MDSC, similar mediators have been
      described in periodontal disease. MDSC promote generation of nitric oxide (NO)
      and reactive oxygen species (ROS). Furthermore, MDSC can differentiate in
      functional osteoclasts. We hypothesize that MDSC are generated during periodontal
      disease. Review of literature evaluating this hypothesis and possible
      implications are assed in this work. It encourages the study of MDSC in this
      common disease.

PMID- 27692165
TI  - In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin
      exposure, promoting a more normal expression of glycolytic and gluconeogenic
      enyzymes and thereby aiding glycemic control.
AB  - In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in
      the context of insulin therapy; as a result, expression of glycolytic enzymes is
      decreased, and that of gluconeogenic enzymes is enhanced, resulting in a
      physiologically inappropriate elevation of hepatic glucose output. Subnormal
      expression of glucokinase (GK) is of particular importance in this regard.
      Possible strategies for correcting this perturbation of hepatic enzyme expression
      include administration of small molecule allosteric activators of GK, as well as
      a procedure known as chronic intermittent intravenous insulin therapy (CIIIT);
      however, side effects accompany the use of GK activators, and CIIIT is time and
      labor intensive. Alternatively, administration of high-dose biotin has potential
      for modulating hepatic enzyme expression in a favorable way. Studies in rodents
      and in cultured hepatocytes demonstrate that, in the context of low insulin
      exposure, supra-physiological levels of biotin induce increased expression of GK
      while suppressing that of the key gluconeogenic enzyme phosphoenolpyruvate
      carboxykinase. These effects may be a downstream consequence of the fact that
      biotin down-regulates mRNA expression of FOXO1; insulin's antagonism of the
      activity of this transcription factor is largely responsible for its modulatory
      impact on hepatic glycolysis and gluconeogenesis. Hence, high-dose biotin may
      compensate for subnormal insulin exposure by suppressing FOXO1 levels. High-dose
      biotin also has the potential to oppose hepatic steatosis by down-regulating
      SREBP-1 expression. Two pilot trials of high-dose biotin (16 or 2mg per day) in
      type 1 diabetics have yielded promising results. There is also some reason to
      suspect that high-dose biotin could aid control of diabetic neuropathy and
      nephropathy via its stimulatory effect on cGMP production. Owing to the safety,
      good tolerance, moderate expense, and current availability of high-dose biotin,
      this strategy merits more extensive evaluation in type 1 diabetes.

PMID- 27692164
TI  - Hair follicle characteristics as early marker of Type 2 Diabetes.
AB  - Type 2 Diabetes mellitus (DM2) includes a continuum of metabolic disorders
      characterized by hyperglycemia that causes several chronic long-term
      complications such as coronary artery disease, peripheral arterial disease,
      nephropathy, and neuropathy. The hair follicle could reveal signs of early
      vascular impairment, yet its relationship to early metabolic injuries has been
      largely ignored. We propose that in earlier stages of the continuum of DM2
      related metabolic disorders, a group of susceptible patients who do not yet meet
      the diagnostic criteria to be considered as persons with DM2 may present chronic
      vascular impairment and end organ damage, including hair follicle damage, which
      can be evaluated to identify an early risk marker. This hypothesis is based in
      the association found between insulin resistance and alopecia in non-diabetic
      persons, and the hair loss on the lower limbs as a manifestation of long-term
      peripheral arterial disease among subjects with DM2. In order to test this
      hypothesis, studies are required to evaluate if hair follicle characteristics are
      related to and can predict hyperglycemic complications, and if they do so, which
      feature of the hair follicle, such as hair growth, best characterizes such DM2
      related conditions. If this hypothesis were proven to be true, significant
      advances towards a personalized approach for early prevention strategies and
      management of DM2 would be made. By focusing on the hair follicles, early stages
      of metabolic-related organ damage could be identified using non-invasive low-cost
      techniques. In so doing, this approach could provide early identification of DM2
      susceptible individuals and lead to the early initiation of adequate primary
      prevention strategies to reduce or avoid the onset of large internal organ
      damage.

PMID- 27692166
TI  - The transition from a rural to an urban environment in Africa alters G protein
      coupled receptor signaling.
AB  - Urbanization in Africa is associated with an increased incidence of non
      communicable diseases, yet the cause and the mechanism remain poorly understood.
      Here, we propose a role for G protein-coupled receptor (GPCR) signaling in the
      biological changes that occur with urbanization and suggest a critical area of
      convergence in GPCR signaling might provide a molecular signature for exposure to
      environmental factors. As a first step in investing this hypothesis, we examined
      the expression of the G protein alpha, beta and gamma subunit, G protein related
      kinase, and beta-arrestin genes in a rural and urban population living in Morocco
      (NCBI GSE8847). Three genes associated with the phosphatidylinositol signaling
      pathway (GNAQ, GNA11 and GNA15), and one gene controlling the cyclic adenosine
      monophosphate pathway (GNAI2) was altered by urbanization. Of note, the
      expression of ARRB1 gene, which encodes the beta-arrestin 1 protein and dampens
      the cellular responses to extracellular signals, was greater in the rural
      compared to the urban population (P<0.00002). These preliminary findings support
      our hypothesis that urbanization fundamentally alters GPCR signaling, resulting
      in both a qualitative and quantitative change in the signaling process. Because
      GPCR signaling is involved in a broad spectrum of cellular functions, further
      research is needed confirm these preliminary findings and to investigate what
      role GPCRs might have in the biological changes that occur with urbanization.

PMID- 27692167
TI  - Peptide-based GLP-1/glucagon co-agonists: A double-edged sword to combat
      diabesity.
AB  - Diabesity is a new term for obesity-dependent diabetes, which is also associated
      with cardiovascular and other comorbidities with rising epidemic. Traditional
      treatments (sulfonylureas and thiazolidinediones) of diabetes are associated with
      weight gain, except metformin. Newer agents such as glucagon-like peptide-1
      receptor agonists (GLP-1 RAs) and Sodium glucose co-transporter 2 inhibitors
      (SGLT2i) are causing a modest weight reduction, whereas dipeptidyl peptidase-4
      inhibitors (DPP-4i) are weight neutral. Oxyntomodulin, a native GLP-1/glucagon
      receptor agonist produced a superior weight loss and antihyperglycemic effects in
      obese mice and humans. Recent findings with synthetic dual GLP-1/glucagon
      receptor agonists have shown a good weight loss and antihyperglycemic profile in
      diet-induced obese (DIO) mice. Targeting combinations of GLP-1 receptor and
      glucagon receptor simultaneously with a single peptide may be the better strategy
      to achieve marked weight loss and considerable glycemic control in diabesity.
      Cardiovascular safety is very important with new antidiabetic agents due to
      rosiglitazone controversy. Current on-going clinical trials will clarify the
      cardiovascular effects of incretin-based therapies in near future. Based on
      current knowledge and rapid progress in the field, there is a strong possibility
      that the GLP-1/glucagon receptor co-agonists will likely be the new therapeutic
      treatment for diabesity for decades to come.

PMID- 27692169
TI  - Proposal for using time estimation training for the treatment of Parkinson's
      disease.
AB  - Studies have shown an association between time perception and the basal ganglia
      and cortical areas, suggesting a role for these regions in the perception of
      seconds, minutes, and hours. We present the hypothesis that time estimation
      training tasks may change the modulatory activity of dopamine in the basal
      ganglia and the cortical areas related to temporal perception. Through this
      mechanism, the estimated training time interval can promote a compensatory effect
      on motor and cognitive performance via a dynamic neural adaptation process. We
      believe that the training will develop a competition between neural pathways
      involved in the process of time perception, positively affecting the brain
      pathways related to Parkinson's disease, and thereby minimizing the cognitive and
      motor deficits caused by the disease.

PMID- 27692170
TI  - Vitamin D regulates the production of vascular endothelial growth factor: A
      triggering cause in the pathogenesis of rheumatic heart disease?
AB  - Rheumatic heart disease (RHD) remains a major cause of cardiac related mortality
      and morbidity in the developing countries due to poor diagnosis and lack of
      proper therapeutics. The definite reason of heart valve injury during RHD is
      poorly understood. Valvular endothelial cells play an important role in
      pathogenesis of different cardiovascular diseases. Besides, the regulation of
      vitamin D (calciferol) and VEGF (vascular endothelial growth factor) results in
      the functional changes in endothelial cells. However, the crosstalk between
      vitamin D and VEGF in the pathogenesis of RHD is not yet unfurled. Evidences in
      the concerned fields are documented by searching through Google Scholar and
      Pubmed. Literature based survey has revealed that vascular endothelium,
      especially endothelial cells play important roles in valvular remodelling during
      cardiovascular diseases. Endothelial cell dysfunction leads to heart valve
      remodelling, which furthermore initiates the pathogenesis of valvular heart
      disease. Vitamin D has the potential to maintain the concentration of VEGF in the
      circulation and induce the function of endothelial cells. Hence, we hypothesize
      that vitamin D and VEGF homeostasis can alter the function of endothelial cells,
      which may subsequently trigger the valvular remodelling or even damage of heart
      valves during the progression of RHD pathogenesis. Our hypothesis shed light on
      the evidence based knowledge translation of plausible cellular phenomena due to
      vitamin D/VEGF homeostasis during valvular vandalism in RHD.

PMID- 27692168
TI  - Does bilirubin prevent hepatic steatosis through activation of the PPARalpha
      nuclear receptor?
AB  - Several large population studies have demonstrated a negative correlation between
      serum bilirubin levels and the development of obesity, hepatic steatosis, and
      cardiovascular disease. Despite the strong correlative data demonstrating the
      protective role of bilirubin, the mechanism by which bilirubin can protect
      against these pathologies remains unknown. Bilirubin has long been known as a
      powerful antioxidant and also has anti-inflammatory actions, each of which may
      contribute to the protection afforded by increased levels. We have recently
      described a novel function of bilirubin as a ligand for the peroxisome
      proliferator-activated receptor-alpha (PPARalpha), which we show specifically
      binds to the nuclear receptor. Bilirubin may function as a selective PPAR
      modulator (SPPARM) to control lipid accumulation and blood glucose. However, it
      is not known to what degree bilirubin activation of PPARalpha is responsible for
      the protection afforded to reduce hepatic steatosis. We hypothesize that
      bilirubin, acting as a novel SPPARM, increases hepatic fatty acid metabolism
      through a PPARalpha-dependent mechanism which reduces hepatic lipid accumulation
      and protects against hepatic steatosis and non-alcoholic fatty liver disease
      (NAFLD).

PMID- 27692171
TI  - Exosomes are possibly used as a tool of immune regulation during the dendritic
      cell-based immune therapy against HIV-I.
AB  - Dendritic cell (DC)-based immune therapy (IT) against HIV showed variable
      results. It is known that different factors influence host response to DC-IT.
      Exosomes derived from DC are regulators of the immune system. In this context,
      here we hypothesize about the role of the DC-derived exosomes on the DC-IT
      response. Based on data from RT-PCR array genes expression (focused on the TSG101
      gene, an exosome marker) and flow cytometry experiments of a DC-IT against HIV-1
      clinical trial, we hypothesize that: During the DC-IT exosomes are used as an
      additional tool for immune system modulation. In addition, we believe that a low
      release of exosomes can be more beneficial for the DC-IT response than a high
      release of exosomes. Our data reinforce the concept that exosomes can act as an
      immune regulatory tool, however not in a generalized manner, but in a highly
      precise way. Our hypothesis is based in preliminary experimental data, thus, it
      should be tested using experimental and functional strategies involving a great
      number of patients. Once the hypothesis confirmed, the immunomodulatory role of
      the exosomes during DC-IT must be considered as an important factor in the (I)
      evaluation, (II) modulation, and (III) success of DC-IT against HIV.

PMID- 27692172
TI  - Cognitive training and Bacopa monnieri: Evidence for a combined intervention to
      alleviate age associated cognitive decline.
AB  - As the elderly population grows the impact of age associated cognitive decline as
      well as neurodegenerative diseases such as Alzheimer's disease and dementia will
      increase. Ageing is associated with consistent impairments in cognitive processes
      (e.g., processing speed, memory, executive function and learning) important for
      work, well-being, life satisfaction and overall participation in society.
      Recently, there has been increased effort to conduct research examining methods
      to improve cognitive function in older citizens. Cognitive training has been
      shown to improve performance in some cognitive domains; including memory,
      processing speed, executive function and attention in older adults. These
      cognitive changes are thought to be related to improvements in brain connectivity
      and neural circuitry. Bacopa monnieri has also been shown to improve specific
      domains of cognition, sensitive to age associated cognitive decline (particularly
      processing speed and memory). These Bacopa monnieri dependent improvements may be
      due to the increase in specific neuro-molecular mechanisms implicated in the
      enhancement of neural connections in the brain (i.e. synaptogenesis). In
      particular, a number of animal studies have shown Bacopa monnieri consumption
      upregulates calcium dependent kinases in the synapse and post-synaptic cell,
      crucial for strengthening and growing connections between neurons. These effects
      have been shown to occur in areas important for cognitive processes, such as the
      hippocampus. As Bacopa monnieri has shown neuro-molecular mechanisms that
      encourage synaptogenesis, while cognitive training enhances brain connectivity,
      Bacopa monnieri supplementation could theoretically enhance and strengthen
      synaptic changes acquired through cognitive training. Therefore, the current
      paper hypothesises that the combination of these two interventions could improve
      cognitive outcomes, over and above the effects of administrating these
      interventions independently, as an effective treatment to ameliorate age
      associated cognitive decline.

PMID- 27692173
TI  - Highly purified calf hemodialysate (Actovegin(r)) may improve endothelial
      function by activation of proteasomes: A hypothesis explaining the possible
      mechanisms of action.
AB  - Highly purified calf hemodialysate (HPCH) known as Actovegin(r) or Solcoseryl(r)
      is one of the most controversial drugs currently marketed worldwide. It is not
      registered as drug in some countries and therefore its medical use there is
      illegal, while in others it is often among the top 10 of the best-selling
      medications. It could be also found in the list of the "most useless drugs" and
      was banned for short time by World Anti-Doping Agency as performance enhancer.
      However, the degree of its usefulness or uselessness remains unclear and there is
      not enough convincing data to make reliable conclusions. HPCH is claimed to have
      wound/muscular injuries healing, neuroprotective and antioxidant properties, to
      enhance glucose uptake and oxygen consumption, and possibly to improve
      performance of athletes. Since HPCH consists of over 200 naturally occurring
      substances which potentially may exert some pharmacological effects, it is
      extremely difficult to perform pharmacokinetic and pharmacodynamical studies. In
      this paper we have analyzed the available literature concerning clinical
      evidence, in vitro, ex vivo and in vivo effects of HPCH. Based on these data we
      suggest that the main target of the drug may be endothelium and improvement of
      endothelial function may be responsible for numerous largely nonspecific effects.
      We also propose the improvement of protein quality control by the means of
      activation of ubiquitin-proteasomal system as the most important biochemical
      mechanism responsible for its effects. The role of sphingolipids as potential
      proteasome-activators is extensively discussed. The effects of HPCH may also
      include direct or indirect ones on NF-kB-, Nrf2- and FOXO-mediated regulation of
      metabolic processes in the cells, which result in improved protein quality
      control, enhanced energy metabolism and increased resistance to oxidative stress.

PMID- 27692174
TI  - Sensing the Environment Through Sestrins: Implications for Cellular Metabolism.
AB  - Sestrins are a family of stress-responsive genes that have evolved to attenuate
      damage induced by stress caused to the cell. By virtue of their antioxidant
      activity, protein products of Sestrin genes prevent the accumulation of reactive
      oxygen species within the cell, thereby attenuating the detrimental effects of
      oxidative stress. In parallel, Sestrins participate in several signaling pathways
      that control the activity of the target of rapamycin protein kinase (TOR). TOR is
      a crucial sensor of intracellular and extracellular conditions that promotes cell
      growth and anabolism when nutrients and growth factors are abundant. In addition
      to reacting to stress-inducing insults, Sestrins also monitor the changes in the
      availability of nutrients, which allows them to serve as a key checkpoint for the
      TOR-regulated signaling pathways. In this review, we will discuss how Sestrins
      integrate signals from numerous stress- and nutrient-responsive signaling
      pathways to orchestrate cellular metabolism and support cell viability.

PMID- 27692175
TI  - Roles and Regulation of Epithelial Splicing Regulatory Proteins 1 and 2 in
      Epithelial-Mesenchymal Transition.
AB  - The transformation of polarized epithelial cells into cells with mesenchymal
      characteristics by the morphogenetic process of epithelial-mesenchymal transition
      (EMT) is a well-characterized process essential for embryonic development and
      associated with cancer progression. EMT is a program driven by changes in gene
      expression induced by several EMT-specific transcription factors, which inhibit
      the expression of cell-cell adhesion proteins and other epithelial markers,
      causing a characteristic loss of cell-cell adhesion, a switch to mesenchymal cell
      morphology, and increased migratory capabilities. Recently, it has become
      apparent that in addition to these transcriptionally regulated changes, EMT may
      also be regulated posttranscriptionally, that is, by alternative splicing.
      Specifically, the epithelial splicing regulatory proteins 1 and 2 (ESRP1 and
      ESRP2) have been described as epithelial-specific splicing master regulators
      specifically involved in EMT-associated alternative splicing. Here, we discuss
      the regulation of ESRP activity, as well as the evidence supporting a causal role
      of ESRPs in EMT.

PMID- 27692177
TI  - The Process of Cornification Evolved From the Initial Keratinization in the
      Epidermis and Epidermal Derivatives of Vertebrates: A New Synthesis and the Case
      of Sauropsids.
AB  - During land adaptation of the integument in tetrapods, an efficient stratum
      corneum was originated through the evolution of numerous corneous proteins in
      addition to the framework of intermediate filament-keratins present in
      keratinocytes. The new genes for corneous proteins were originated in a
      chromosome region indicated as epidermal differentiation complex (EDC), a locus
      with no apparent relationship to keratin genes. The addition of EDC proteins to
      IF-keratins transformed the process of epidermal keratinization present in
      anamniotes into a new process of cornification in the epidermis and skin
      appendages of amniotes, including hairs and feathers. In sauropsids among other
      EDC proteins a peculiar type of small proteins evolved a central region of 34
      amino acids conformed as beta-sheets that, differently from the other EDC
      proteins, allowed the formation of long polymers of filamentous proteins
      customarily termed beta-keratins but in the present review reclassified as EDC
      corneous beta proteins. To the initial beta-sheets present in the corneous beta
      proteins specific N- and C-regions were later added in the proteins of different
      sauropsids in relation to the evolution of the corneous layer and skin
      appendages. Cornification contributed to the evolutive success of amniotes in the
      terrestrial environment.

PMID- 27692178
TI  - The Calcium-Sensing Receptor in Health and Disease.
AB  - The extracellular calcium-sensing receptor (CaSR) is a unique G protein-coupled
      receptor (GPCR) activated by extracellular Ca2+ and by other physiological
      cations including Mg2+, amino acids, and polyamines. CaSR is the most important
      master controller of the extracellular Ca2+ homeostatic system being expressed at
      high levels in the parathyroid gland, kidney, gut and bone, where it regulates
      parathyroid hormone (PTH) secretion, vitamin D synthesis, and Ca2+ absorption and
      resorption, respectively. Gain and loss of function mutations in the CaSR are
      responsible for severe disturbances in extracellular Ca2+ metabolism. CaSR
      agonists (calcimimetics) and antagonists (calcilytics) are in use or under
      intense research for treatment of hyperparathyroidism secondary to kidney failure
      and hypocalcemia with hypercalciuria, respectively. Expression of the CaSR
      extends to other tissues and systems beyond the extracellular Ca2+ homeostatic
      system including the cardiovascular system, the airways, and the nervous system
      where it may play physiological functions yet to be fully understood. As a
      consequence, CaSR has been recently involved in different pathologies including
      uncontrolled blood pressure, vascular calcification, asthma, and Alzheimer's
      disease. Finally, the CaSR has been shown to play a critical role in cancer
      either contributing to bone metastasis and/or acting as a tumor suppressor in
      some forms of cancer (parathyroid cancer, colon cancer, and neuroblastoma) and as
      oncogene in others (breast and prostate cancers). Here we review the role of CaSR
      in health and disease in calciotropic tissues and others beyond the extracellular
      calcium homeostatic system.

PMID- 27692179
TI  - Molecular Interactions Between Flowering Time and Abiotic Stress Pathways.
AB  - Plants have adapted to environmental changes and stresses over generations. The
      decision of transition from the vegetative to reproductive stage is critical,
      particularly under unfavorable conditions. Thus, plants appear to have developed
      mechanisms by which environmental factors or inputs are transmitted to stress
      response signaling pathways to confer tolerance and are simultaneously integrated
      into flowering regulation pathways (photoperiod, vernalization, autonomous, and
      gibberellic acid signaling) to propagate the next generation. In this review, we
      summarize how abiotic stresses influence, induce, or delay flowering time,
      particularly in the long-day plant Arabidopsis. Four major modes including
      FLOWERING LOCUS C (FLC), CONSTANS (CO), DELLA, and GIGANTEA (GI), which serve as
      hubs that integrate stress signals for regulating flowering time, are introduced.
      GI, a mediator of the photoperiod floral pathway and circadian clock, is involved
      in various biological processes and thus controls stress response directly
      through interaction with stress-responsive components and indirectly through
      association with circadian clock components.

PMID- 27692181
TI  - A Mechanistic Approach to the Development of Gene Therapy for Chronic Pain.
AB  - Treatment of chronic pain has created a "silent epidemic," a term that describes
      the serious public health problem of the abuse of opioid painkillers and other
      prescription drugs. Conventional pharmacotherapy is limited by the loss of
      effectiveness in the long-term and by potentially lethal side effects. Efforts
      need to be focused on the development of nonpharmacological approaches. As
      significant progress is made in the viral vector technology, gene therapy
      involving recombinant viruses as vehicles may become a viable alternative for
      treatment of severe pain. Virus-based gene therapy has several advantages: (1)
      the transfer of a therapeutic gene to produce/release bioactive therapeutic
      molecules in a specific location in the nervous system thus minimizing the risks
      of off-target side effects, and (2) sustained long-term production of the
      therapeutic agent. This review compiles recently developed strategies for gene
      therapy targeting specific mechanisms of specific chronic pain conditions. A few
      successful studies on animal models of chronic pain have been translated to human
      clinical trials.

PMID- 27692182
TI  - Community-Based Methadone Maintenance in a Large Detention Center is Associated
      with Decreases in Inmate Recidivism.
AB  - Because it is not common in the U.S. for jails to allow inmates to continue
      opioid medications that have been started in the community, we aimed to assess
      whether inmates maintained on methadone showed different rates of recidivism,
      lengths of incarceration, and types of offenses than other incarcerated groups.
      We also analyzed rates of return to home clinics after release. In order to
      answer these questions this study used extant data from 960 adult inmates in a
      large metropolitan detention center who were in 1 of 4 groups: general population
      with no known substance use disorders, alcohol detoxification, methadone
      maintenance (MMT), and opioid detoxification. Recidivism was assessed for 1 year
      after release. Data were collected from medical screening forms and jail
      databases and included demographic variables, dates of admission and release,
      number of doses and total dosage of methadone if applicable, reason for
      incarceration, and the date of rebooking and nature of offense, if it occurred.
      There was a significant difference in time to rebooking, F (3956)=13.32, p=.00,
      with the MMT group taking longer to be rebooked (275.6 days) than the opioid
      (236.3 days) and alcohol detoxification groups (229.3 days), but not the general
      population group (286.2 days). Survival analysis indicated significantly better
      survival without rebooking in the MMT and general population groups than the
      alcohol and opioid detoxification groups. There also were differences in length
      of incarceration, F (3, 954)=9.02, p=.00, with the MMT group being incarcerated
      longer than other substance using groups; and in misdemeanor vs. felony rebooking
      offenses, chi2 [3]=31.29, p<.01, with the opioid detoxification group being more
      likely to have a felony rebooking than the general or alcohol groups. In a
      separate analysis, data from 137 MMT clients, who were not precisely the same
      clients who were involved in other analyses reported in this article, indicated
      that over 97% returned to their home methadone clinics after incarceration. In
      summary, inmates who had been allowed to be maintained on methadone started in
      the community displayed a significantly longer time to be rearrested than inmates
      undergoing opioid or alcohol detoxification, but not inmates without substance
      use disorders. When they were rebooked, they were as likely as the opioid
      detoxification group to be rearrested for felony offenses.

PMID- 27692183
TI  - Primary Care Providers' Interest in Using a Genetic Test to Guide Alcohol Use
      Disorder Treatment.
AB  - BACKGROUND: Efforts to identify genetic moderators of pharmacotherapy response
      have generated interest in clinical applications of pharmacogenetic tests in
      alcohol use disorder (AUD) treatment. To date, no research on providers' interest
      in using pharmacogenetic tests in the context of AUD treatment has been reported.
      We conducted qualitative interviews with primary care providers from 5 clinics in
      the Veterans Health Administration (VA) to assess their interest in using a
      hypothetical genetic test to inform treatment of AUD with pharmacotherapy.
      METHODS: Key contacts were used to recruit 24 providers from 5 primary care
      clinics associated with a single large VA medical facility. Participants
      completed 30-minute in-person semi-structured interviews focused on barriers and
      facilitators to provision of pharmacotherapy for AUD. Interviews included a
      hypothetical scenario regarding the availability of a genetic test to inform AUD
      pharmacotherapy provision and/or selection. Provider responses to the
      hypothetical scenario were recorded, transcribed and analyzed qualitatively using
      inductive content analysis. Data were independently coded by three investigators,
      and themes were identified via consensus. RESULTS: Participants were generally
      interested in a genetic test to aid in AUD treatment planning. Five common themes
      were identified, including: perceived benefits of a pharmacogenetic test (e.g.,
      aiding with therapeutic choice, positively impacting patient motivation for and
      engagement with AUD treatment), perceived drawbacks (e.g., limiting potential
      benefits of pharmacotherapy by reducing the target population for its receipt,
      adverse impacts of "negative" results), caveats to clinical utility (e.g.,
      utility would depend on prognostic accuracy and/or medication characteristics),
      uncertainty as to whether such a test would impact clinical decision-making, and
      pragmatic barriers to use (costs and other resources, such as laboratory
      facilities). CONCLUSIONS: Primary care providers in this study generally believed
      a genetic test to aid in AUD treatment planning would be useful, due to its
      potential to hone treatment choice as well as to influence patient motivation and
      adherence to treatment. However, providers acknowledged that a test's utility
      would depend on the strength of its prognostic characteristics, its other
      benefits relative to standard care, and lack of pragmatic barriers.

PMID- 27692176
TI  - Orchestrating Lymphocyte Polarity in Cognate Immune Cell-Cell Interactions.
AB  - The immune synapse (IS) is a specialized structure established between different
      immune cells that fulfills several functions, including a role as a communication
      bridge. This intimate contact between a T cell and an antigen-presenting cell
      promotes the proliferation and differentiation of lymphocytes involved in the
      contact. T-cell activation requires the specific triggering of the T-cell
      receptor (TCR), which promotes the activation of different signaling pathways
      inducing the polarization of the T cell. During this process, different adhesion
      and signaling receptors reorganize at specialized membrane domains, concomitantly
      to the polarization of the tubulin and actin cytoskeletons, forming stable
      polarization platforms. The centrosome also moves toward the IS, driving the
      movement of different organelles, such as the biosynthetic, secretory, degrading
      machinery, and mitochondria, to sustain T-cell activation. A proper orchestration
      of all these events is essential for T-cell effector functions and the
      accomplishment of a complete immune response.

PMID- 27692180
TI  - Metabolic Regulation of Apoptosis in Cancer.
AB  - Apoptosis is a cellular suicide program that plays a critical role in development
      and human diseases, including cancer. Cancer cells evade apoptosis, thereby
      enabling excessive proliferation, survival under hypoxic conditions, and acquired
      resistance to therapeutic agents. Among various mechanisms that contribute to the
      evasion of apoptosis in cancer, metabolism is emerging as one of the key factors.
      Cellular metabolites can regulate functions of pro- and antiapoptotic proteins.
      In turn, p53, a regulator of apoptosis, also controls metabolism by limiting
      glycolysis and facilitating mitochondrial respiration. Consequently, with
      dysregulated metabolism and p53 inactivation, cancer cells are well-equipped to
      disable the apoptotic machinery. In this article, we review how cellular
      apoptosis is regulated and how metabolism can influence the signaling pathways
      leading to apoptosis, especially focusing on how glucose and lipid metabolism are
      altered in cancer cells and how these alterations can impact the apoptotic
      pathways.

PMID- 27692184
TI  - Smoking Cessation and Adolescent Treatment Response With Comorbid ADHD.
AB  - Minors entering treatment for alcohol and other drug (AOD) use disorders tend to
      smoke at high rates, and many have comorbid attention deficit hyperactivity
      disorder (ADHD). Clear-air laws force patients to refrain from smoking on the
      premises of AOD treatment facilities, which may hinder the progress of treatment
      seeking populations who smoke and struggle with ADHD comorbidity in particular.
      This study explores clinical characteristics associated with smoking among youths
      presenting for residential treatment, clinical characteristics associated with
      smoking cessation, and the impact of smoking cessation with ADHD comorbidity on
      AOD treatment response. Participants were 195 adolescents (52% female, aged 14-18
      years) court-referred to residential treatment. Data were collected at intake,
      prospectively each week for the 10-week treatment period, and at discharge. Two
      thirds (67%) of the enrollment sample entered treatment smoking half a pack a day
      on average, a large proportion (50%) of which did not smoke during treatment.
      ADHD patients were more likely to smoke before and during treatment except for
      those who got active in service and step-work. Quitting smoking did not adversely
      affect AOD outcomes and was associated with better prognosis of lowered AOD
      cravings for youths with and without ADHD. Smoking cessation during adolescent
      AOD treatment is recommended with provision of pharmaceutical and/or behavioral
      modalities that reduce nicotine withdrawal.

PMID- 27692185
TI  - The Alcohol Intervention Mechanisms Scale (AIMS): Preliminary Reliability and
      Validity of a Common Factor Observational Rating Measure.
AB  - The present work provides an overview, and pilot reliability and validity for the
      Alcohol Intervention Mechanisms Scale (AIMS). The AIMS measures therapist
      interventions that occur broadly across modalities of behavioral treatment for
      alcohol use disorder. It was developed based on identified commonalities in the
      function rather than content of therapist interventions in observed therapy
      sessions, as well as from existing observer rating systems. In the AIMS, the
      primary function areas are: explore (four behavior count codes), teach (five
      behavior count codes), and connect (three behavior count codes). Therapist
      behavior counts provide a frequency rating of occurrence (i.e., adherence). The
      three functions (explore, teach, connect) are then rated on global skillfulness,
      which provides a quality valence (i.e., competence) to the entire session. In the
      present study, three independent raters received roughly 30 hours of training on
      the use of the AIMS by the first author. Data were a sample of therapy session
      audio files from a Project MATCH clinical research site. Reliability results
      showed generally good performance for the measure. Specifically, 2-way mixed
      intraclass coefficients were 'excellent', ranging from .94 to .99 for function
      summary scores, while prevalence-adjusted, bias-adjusted kappa for global
      skillfulness measures were in the 'fair' to 'moderate' range (k=.36 to.40).
      Internal consistency reliability was acceptable, as were preliminary factor
      models by behavioral treatment function (i.e., explore, teach, connect). However,
      confirmatory fit for the subsequent three factor model was poor. In concurrent
      validity analyses, AIMS summary and skillfulness scores showed associations with
      relevant Project MATCH criterion measures (i.e., MATCH Tape Rating Scale) that
      were consistent with expectations. The AIMS is a promising and reliable
      observational measure of three proposed common functions of behavioral alcohol
      treatment.

PMID- 27692186
TI  - A survey of Physicians' Perspectives on the New York State Mandatory Prescription
      Monitoring Program (ISTOP).
AB  - BACKGROUND: Prescription drug monitoring programs (PDMPs) have emerged as one
      tool to combat prescription drug misuse and diversion. New York State mandates
      that prescribers use its PDMP (called ISTOP) before prescribing controlled
      substances. We surveyed physicians to assess their experiences with mandatory
      PDMP use. METHODS: Electronic survey of attending physicians, from multiple
      clinical specialties, at one large urban academic medical center. RESULTS: Of 207
      responding physicians, 89.4% had heard of ISTOP, and of those, 91.1% were
      registered users. 45.7% of respondents used the system once per week or more.
      There was significant negative feedback, with 40.4% of respondents describing
      ISTOP as "rarely" or "never helpful," and 39.4% describing it as "difficult" or
      "very difficult" to use. Physicians expressed frustration with the login process,
      the complexity of querying patients, and the lack of integration with electronic
      medical records. Only 83.1% knew that ISTOP use is mandated in almost all
      situations. A minority agreed with this mandate (44.2%); surgeons, males, and
      those who prescribe controlled substances at least once per week had
      significantly lower rates of agreement (22.6%, 36.2%, and 33.0%, respectively).
      The most common reasons for disagreement were: time burden, concerns about
      helpfulness, potential for under-treatment, and erosion of physician autonomy.
      Emergency physicians, who are largely exempt from the mandate, were the most
      likely to believe that ISTOP was helpful, yet the least likely to be registered
      users. 48.4% of non-emergency physicians reported perfect compliance with the
      mandate; surgeons and males reported significantly lower rates of perfect
      compliance (18.2% and 36.8%, respectively). CONCLUSIONS: This study offers a
      unique window into how one academic medical faculty has experienced New York's
      mandatory PDMP. Many respondents believe that ISTOP is cumbersome and generally
      unhelpful. Furthermore, many disagree with, and don't comply with, its mandatory
      use.

PMID- 27692187
TI  - Staff Perceptions of Substance Use Disorder Treatment in VA Primary Care-Mental
      Health Integrated Clinics.
AB  - INTRODUCTION: Guidelines recommend that substance use disorder (SUD) treatment be
      available in primary care-mental health integrated clinics, which offer mental
      and behavioral health assessment and treatment in the primary care setting.
      Despite this recommendation it is unclear what barriers and facilitators exist to
      SUD treatment being provided in that setting. This work sought to understand
      current SUD services in such integrated clinics, explore other services may that
      be appropriate, and identify barriers to such services. METHODS: We conducted
      qualitative interviews with 23 staff members from integrated clinics at 6
      Veterans Affairs medical centers. We transcribed interviews and performed
      thematic analysis to identify emergent themes. RESULTS: We identified seven
      themes affecting staff experience and ability to provide SUD services in the
      integrated clinic: clinical effectiveness, clinical requirements, regulatory
      requirements, program goals, proximity of the integrated clinic and SUD services,
      training on substance use disorder, and role specialization. CONCLUSIONS: VA
      primary care-mental health integrated clinic staff members do not currently view
      SUD treatment as the focus of their work, but are open to offering SUD treatment
      including brief psychological interventions or medication. Several barriers to
      providing SUD treatment were identified, including the need for additional staff
      training around appropriate interventions for the integrated clinic setting,
      additional staffing and space, and a structured implementation strategy to
      promote the use of SUD treatments.

PMID- 27692188
TI  - A Naturalistic Evaluation of Extended-Release Naltrexone in Clinical Practice in
      Missouri.
AB  - The purpose of this study was to compare the naturalistic outcomes of individuals
      with alcohol or opioid use problems who were treated with extended-release
      naltrexone (XR-NTX) to those treated with psychosocial treatment only and also to
      those treated with other medication-assisted therapies in Missouri during 2010 to
      2011. We analyzed intake and discharge data collected as part of SAMHSA's
      Treatment Episode Data Set assessments. Patients who received XR-NTX during their
      treatment episode were compared, for those reporting alcohol (but not opioids) as
      their problem (N=21,137), to those who received oral naltrexone, acamprosate, and
      psychosocial treatment only, and for those who reported opioids as a problem
      (N=8996), to those receiving oral naltrexone, buprenorphine/naloxone, and
      psychosocial treatment only. Group differences were adjusted using propensity
      score weighting, with propensity scores derived from 18 intake variables. For the
      alcohol sample, patients who received XR-NTX vs. the oral naltrexone group had
      superior composite outcomes on a measure combining abstinence, self-help
      participation, employment, and arrests. For the opioid sample, XR-NTX was found
      to have significantly better outcomes than oral naltrexone on the composite
      outcome measure. For both the alcohol and opioid samples, the group that received
      XR-NTX stayed in treatment longer vs. psychosocial treatment only. In the opioid
      sample, those receiving buprenorphine/naloxone remained in treatment longer than
      those receiving XR-NTX.

PMID- 27692189
TI  - Monitoring a Prison Opioid Treatment Program Over a Period of Change to Clinical
      Governance Arrangements, 2007-2013.
AB  - BACKGROUND AND AIMS: Opioid substitution therapy (OST) is an effective treatment
      for opioid dependence that is provided in many correctional settings, including
      New South Wales (NSW), Australia. In 2011, changes to the clinical governance of
      the NSW prison OST program were implemented, including a more comprehensive
      assessment, additional specialist nurses, and centralization of program
      management and planning. This study aimed to document the NSW prison OST program,
      and assess the impact of the enhanced clinical governance arrangements on
      retention in treatment until release, the provision of an OST prescription to
      patients at release, and presentation to a community OST clinic within 48 hours
      of release from custody. METHOD: Data from the NSW prison OST program were
      obtained for the calendar years 2007-2013. Outcomes were analyzed quarterly using
      log binomial segmented regression. RESULTS: 8577 people were treated with OST in
      NSW correctional centers, 2007-2013. Over the entire study period, patients were
      retained in OST until release in 82% of treatment episodes; a prescription for
      OST was able to be arranged prior to release in 90% of releases; and patients
      presented to a community clinic within 48 hours of release in 94% of releases
      with prescriptions. Following the introduction of the changes to clinical
      governance, there was a significant increasing trend in retention in OST until
      release, and in provision of an OST prescription at release. There was an initial
      increase, followed by a decreasing trend, in presentation to a community clinic
      within 48 hours of release. DISCUSSION: This large prison-based OST program has
      high rates of retention in treatment and continuity of care as patients
      transition from custody to the community. Strengthened clinical governance
      arrangements were associated with increased retention in treatment until release
      and increased provision of an OST prescription at release, but did not improve
      clinic attendance following release from custody.

PMID- 27692190
TI  - Transitioning From Detoxification to Substance Use Disorder Treatment:
      Facilitators and Barriers.
AB  - Although successful transitions from detoxification to substance use disorder
      treatment are associated with improved outcomes, many detoxification patients do
      not initiate treatment. This qualitative study informs detoxification and
      addiction treatment providers, and health systems, about how to improve
      detoxification to treatment transitions, by reporting detoxification providers'
      views of transition facilitators and barriers. The sample consisted of 30
      providers from 30 Veterans Health Administration detoxification programs. Themes
      regarding transition facilitators and barriers emerged at the patient, program
      (detoxification programs, and addiction programs), and system levels.
      Detoxification program-level practices of discharge planning, patient education,
      and rapport building were reported as facilitating the transition to treatment.
      Six themes captured transition facilitators within addiction treatment programs:
      the provision of evidence-based practices, patient-centered care, care
      coordination, aftercare, convenience, and a well-trained and professional staff.
      This study expands previous literature on detoxification and addiction treatment
      by systematically and qualitatively examining factors that promote and hinder
      treatment initiation after inpatient and outpatient detoxification, from a
      provider perspective, in an era of health care reform and expanded substance use
      disorder treatment.

PMID- 27692191
TI  - Semantic Networks, Schema Change, and Reincarceration Outcomes of Therapeutic
      Community Graduates.
AB  - BACKGROUND: Therapeutic community (TC) clinical theory assumes that peer
      interaction forms a framework for social learning that will displace ingrained
      cognitive schema that underlie substance abuse. There has been no direct test of
      this hypothesis. METHODS: We analyzed the content of a large corpus of written
      affirmations (pushups) and corrections (pull-ups) exchanged between 2342 male TC
      graduates. We encoded the content of the written communications as semantic
      networks of words, in which words that appear in the same brief document are
      connected and are referred to as word combinations. Loss of combinations and gain
      of combinations each measured an aspect of change in word combination patterns
      across time. These measures were used in a multivariable Cox model to predict the
      hazard of reincarceration for residents while controlling for race, age, score on
      the Level of Service Inventory-Revised and the total number of pushups and pull
      ups sent to peers. RESULTS: Residents' reincarceration risk varied significantly
      with changes in word combinations used over the course of treatment. The
      implications of the model were visualized to reveal the complicated nature of the
      interaction terms included in the model. The visuals suggested that residents who
      changed their expression patterns the least - lost and gained few word
      combinations - had the highest reincarceration risk after graduation.
      CONCLUSIONS: The results suggest that TC success, in terms of increasing time to
      reincarceration, depends on how residents change their interaction patterns
      through the treatment process. Merely interacting with others does not explain
      success; but whether those interactions change does explain outcomes, which may
      imply that more fundamental changes are occurring.

PMID- 27692193
TI  - Non-Prescribed Buprenorphine in New York City: Motivations for Use, Practices of
      Diversion, and Experiences of Stigma.
AB  - Non-medical use of opioid analgesics (OAs) has increased in the United States
      over the past decade. Concurrently, access to opioid agonist therapies (OATs)
      such as buprenorphine has expanded. However, there has been little in-depth
      qualitative exploration into circumstances surrounding buprenorphine diversion
      and non-prescribed use. This study reports on qualitative data from in-depth
      interviews conducted with persons in New York City reporting non-medical OA use
      in the past 12 months. Participants (n=42) were aged between 18 and 49 years. The
      majority were male (n=29) and non-Hispanic White (n=35). All participants self
      reported physical opioid dependence. Motivations for non-prescribed buprenorphine
      use included the abatement of withdrawal symptoms or a self-initiated
      detoxification or treatment plan. Few participants reported buprenorphine use for
      euphoric effect, and no participants reported using buprenorphine as a primary
      drug. Buprenorphine diversion primarily occurred as a means of supporting ongoing
      illicit drug use, and no participants reported selling buprenorphine as a primary
      source of income. Participants reported misinformation around some key areas of
      buprenorphine induction and use, as well as stigma within peer networks and from
      drug treatment providers. As access to buprenorphine treatment continues to
      expand in the United States, enhancing patient education is a critical step
      toward minimizing diversion and incidental harms from non-prescribed use.

PMID- 27692192
TI  - Mortality Rates Among Substance Use Disorder Participants in Clinical Trials:
      Pooled Analysis of Twenty-Two Clinical Trials Within the National Drug Abuse
      Treatment Clinical Trials Network.
AB  - BACKGROUND: Most substance use disorders (SUD) treatment clinical trials are too
      short and small to reliably estimate the incidence of rare events like death.
      OBJECTIVE: The aim of this study is to estimate the overall mortality rates among
      a SUD treatment-seeking population by pooling participants from multiple clinical
      trials conducted through the National Institute on Drug Abuse (NIDA)-sponsored
      National Drug Abuse Treatment Clinical Trials Network (CTN). PARTICIPANTS: Drug
      and or alcohol users (N=9866) who sought treatment and participated in one of the
      twenty-two CTN trials. MEASUREMENTS: Data were collected through randomized
      clinical trials in national community treatment programs for SUD. Pooled analysis
      was performed to assess age- and gender-standardized mortality rate(s) (SM
      rate(s)), and mortality ratio(s) (SM ratio(s)) of CTN trial participants compared
      to the U.S. general population. RESULTS: The age- and gender-SM rate among CTN
      trials participants was 1403 (95% CI: 862-2074) per 100,000 person years (PY)
      compared to 542 (95% CI: 541-543) per 100,000 PY among the U.S. general
      population in 2005. By gender, age-adjusted SM ratio for female CTN trial
      participants was over five times (SM ratio=5.35, 95% CI: 3.31-8.19)), and for
      male CTN trial participants, it was over three times (SM ratio=3.39, 95% CI: 2.25
      4.90) higher than their gender comparable peers in the U.S. general population.
      CONCLUSIONS: Age and gender-standardized mortality rates and ratios among NIDA
      CTN SUD treatment-seeking clinical trial participants are higher than the age and
      gender comparable U.S. general population. The overall mortality rates of CTN
      trial participants are similar to in-treatment mortality reported in large U.S.
      and non-U.S. cohorts of opioid users. Future analysis with additional CTN trial
      participants and risk times will improve the stability of estimates, especially
      within subgroups based on primary substance of abuse. These SUD mortality rates
      can be used to facilitate safety monitoring within SUD clinical trials.

PMID- 27692194
TI  - Presence of Drug-Free Family and Friends in the Personal Social Networks of
      People Receiving Treatment for Opioid Use Disorder.
AB  - The present study evaluated the presence of drug-free family and friends in the
      personal social networks of individuals seeking treatment for opioid use
      disorder, and the willingness of patients to bring these individuals to the
      treatment program to support recovery efforts. Patients at a community medication
      assisted treatment program (n=355) completed a clinical survey to identify drug
      free social network members. Results showed that almost all patients (98%)
      reported having at least one drug-free family or friend in their personal network
      (M=3.7), and that these network members often lived in relatively close proximity
      to the patient (M distance of closest member =1.8 miles). About a quarter of
      these individuals (26%) had a history of substance use problems, with 10% of the
      entire sample currently receiving treatment for a substance use problem. Rates of
      drug-free network members varied across several baseline characteristics. Most
      patients (89%) reported a willingness to invite at least one drug-free network
      member into treatment to support recovery efforts. Mobilizing drug-free network
      family and friends may provide a pathway to help individuals with substance use
      disorders access and benefit from community support.

PMID- 27692195
TI  - The History of Sympathetic Surgery.
AB  - At present, primary hyperhidrosis is the main indication for sympathectomy. For
      upper thoracic sympathetic ablation, excision of the second thoracic ganglion
      alone or with the first and/or third ganglia was the standard during the open
      surgery era. With the advent of thoracoscopy, modifications related to the level,
      extent, and type of ablation were proposed to attenuate compensatory
      hyperhidrosis. The ideal operation for sympathetic denervation of the face and
      upper limbs remain to be defined. Controlled double-blind studies with quantitave
      measurements of sweat production are required.

PMID- 27692196
TI  - Pathophysiology of Hyperhidrosis.
AB  - Studies and case reports on excessive sweating frequently state that
      hyperhidrosis is a disease whose origin and mechanism are unknown. However, the
      term excessive is rarely based on systematic diagnostic measurements, instead
      being a description of the symptoms from patient histories, which suggests that
      hyperhidrosis is purely a problem involving the quantity of sweat, whereas it is
      a change in the control mechanism of sweating in which the need for and
      production of sweat are strongly disproportionate. This lack of proportion is
      perceived by those affected to be a limitation of activities of daily living and
      is thus pathologic.

PMID- 27692197
TI  - Emerging Nonsurgical Treatments for Hyperhidrosis.
AB  - A variety of available treatment options are available for primary focal
      hyperhidrosis, and some can be combined to obtain maximum effective results. Most
      treatment options have only been studied in patients with axillary hyperhidrosis,
      and more studies are needed to develop therapies for other body regions. Several
      clinical trials are underway with promising preliminary results; however, there
      is still a large need for new therapies.

PMID- 27692198
TI  - Selecting the Right Patient for Surgical Treatment of Hyperhidrosis.
AB  - This article presents a personal view of the indications for surgical treatment
      of patients with hyperhidrosis based on long clinical experience. Endoscopic
      thoracic sympathectomy is the preferred opinion for palmar sweating. It is also
      useful when there is additional axillary sweating but is not the first choice for
      isolated armpit symptoms. Surgical treatment of craniofacial sweating is much
      more likely to be followed by undesirable side-effects.

PMID- 27692199
TI  - Targeting the Sympathetic Chain for Primary Hyperhidrosis: An Evidence-Based
      Review.
AB  - Large case series and randomized trials over the past 25 years have consistently
      demonstrated thoracoscopic interruption of the sympathetic chain to be a safe and
      effective treatment of focal primary hyperhidrosis. The surgical technique has
      evolved toward less-invasive and less-extensive procedures in an effort to
      minimize perioperative morbidity and effectively balance postoperative
      compensatory sweating with symptomatic relief. This review summarizes available
      evidence regarding the surgical approach and the optimal level of interruption of
      the sympathetic chain based on a patient's presenting distribution of pathologic
      sweating.

PMID- 27692200
TI  - Reversibility of Sympathectomy for Primary Hyperhidrosis.
AB  - Endoscopic thoracic sympathectomy (ETS) is an effective treatment of primary
      hyperhidrosis of the face, upper extremities, and axillae. The major limitation
      is the side effect of compensatory sweating severe enough that patients request
      reversal in up to 10% of cases. When ETS is performed by cutting the sympathetic
      chain, reversal requires nerve grafting. However, for ETS done with clips,
      reversal is a simple thoracoscopic outpatient procedure of removing the clips.
      Subsequent reversal of the sympathectomy, ie, nerve regeneration, is successful
      in many cases. However, follow-up is short. Factors contributing to success rates
      require further study.

PMID- 27692201
TI  - Reconstruction of the Sympathetic Chain.
AB  - There is a small subset of patients who have undergone endoscopic thoracic
      sympathectomy for hyperhidrosis or facial blushing who are dissatisfied and would
      wish reversal. Compensatory sweating is the most common side effect that causes a
      person to regret surgery. Treatment options are limited and usually not effective
      in patients with severe side effects from sympathectomy. Nerve graft
      interposition has been proven to be effective in experimental models and small
      clinical series. Da Vinci robotic nerve graft reconstruction with interposition
      graft and direct suturing of nerve and high magnification dissection most closely
      mirrors standard nerve reconstruction principles when done as a minimally
      invasive procedure.

PMID- 27692202
TI  - Quality of Life Changes Following Surgery for Hyperhidrosis.
AB  - The best way to evaluate the impact of primary hyperhidrosis on quality of life
      (QL) is through specific questionnaires, avoiding generic models that do not
      appropriately evaluate individuals. QL improves significantly in the short term
      after sympathectomy. In the longer term, a sustained and stable improvement is
      seen, although there is a small decline in the numbers; after 5 and even at 10
      years of follow-up it shows virtually the same numerical distribution.
      Compensatory hyperhidrosis is a major side effect and the main aggravating factor
      in postoperative QL, requiring attention to its management and prevention.

PMID- 27692203
TI  - Management of Compensatory Sweating After Sympathetic Surgery.
AB  - Compensatory hyperhidrosis (HH) is the most common and feared side effect of
      thoracic sympathectomy, because patients with severe forms have their quality of
      life greatly impaired. The most well-known factors associated with compensatory
      HH are extension of manipulation of the sympathetic chain, level of sympathetic
      denervation, and body mass index. Technical developments as well as the proper
      selection of patients for surgery have been crucial in reducing the occurrence of
      severe forms of compensatory HH. Therapeutic options include topical agents,
      botulinum toxin, systemic anticholinergics, clip removal, and sympathetic chain
      reconstruction, although the efficacy is not well-established for all the
      methods.

PMID- 27692204
TI  - Less Common Side Effects of Sympathetic Surgery.
AB  - Because of video-assisted thoracic technology and increased patient awareness of
      treatment options for palmar hyperhidrosis, endoscopic thoracic sympathectomy
      (ETS) has become a well-accepted treatment for this disorder. Video assistance
      affords excellent visualization of thoracic anatomy, which allows the procedure
      to be done quickly with few complications. However, despite the ease of
      performing ETS, complications can occur unless thoracic anatomy and physiology
      are well-understood. Awareness of possible intraoperative and postoperative
      complications is essential if this procedure is gong to be performed safely.

PMID- 27692205
TI  - Facial Blushing: Patient Selection and Long-Term Results.
AB  - Facial blushing, associated with social phobia, may have severe negative impact
      on the quality of daily life. The first line of treatment should be psychological
      and/or pharmacologic. In severe cases not responding to nonsurgical treatment,
      surgical sympathetic denervation is an option. A thorough disclosure of effects,
      complications, and side effects is mandatory and patient selection is crucial to
      obtain high patient satisfaction from surgical treatment.

PMID- 27692206
TI  - Management of Plantar Hyperhidrosis with Endoscopic Lumbar Sympathectomy.
AB  - Primary plantar hyperhidrosis is defined as excessive secretion of the sweat
      glands of the feet and may lead to significant limitations in private and
      professional lifestyle and reduction of health-related quality of life.
      Conservative therapy measures usually fail to provide sufficient relieve of
      symptoms and do not allow long-lasting elimination of hyperhidrosis. Endoscopic
      lumbar sympathectomy appears to be a safe and effective procedure for eliminating
      excessive sweating of the feet and improves quality of life of patients with
      severe plantar hyperhidrosis.

PMID- 27692207
TI  - Hyperhidrosis.

PMID- 27692208
TI  - Graph-based inductive reasoning.
AB  - This article discusses methods of inductive inferences that are methods of
      visualizations designed in such a way that the "eye" can be employed as a
      reliable tool for judgment. The term "eye" is used as a stand-in for visual
      cognition and perceptual processing. In this paper "meaningfulness" has a
      particular meaning, namely accuracy, which is closeness to truth. Accuracy
      consists of precision and unbiasedness. Precision is dealt with by statistical
      methods, but for unbiasedness one needs expert judgment. The common view at the
      beginning of the twentieth century was to make the most efficient use of this
      kind of judgment by representing the data in shapes and forms in such a way that
      the "eye" can function as a reliable judge to reduce bias. The need for judgment
      of the "eye" is even more necessary when the background conditions of the
      observations are heterogeneous. Statistical procedures require a certain minimal
      level of homogeneity, but the "eye" does not. The "eye" is an adequate tool for
      assessing topological similarities when, due to heterogeneity of the data, metric
      assessment is not possible. In fact, graphical assessments precedes measurement,
      or to put it more forcefully, the graphic method is a necessary prerequisite for
      measurement.

PMID- 27692209
TI  - Structural realism beyond physics.
AB  - The main purpose of this paper is to test structural realism against (one example
      from) the historical record. I begin by laying out an existing challenge to
      structural realism - that of providing an example of a theory exhibiting
      successful structures that were abandoned - and show that this challenge can be
      met by the miasma theory of disease. However, rather than concluding that this is
      an outright counterexample to structural realism, I use this case to show why it
      is that structural realism, in its current form, has trouble dealing with
      theories outside physics. I end by making some concrete suggestions for
      structural realists to pursue if, indeed, they are serious about extending
      structural realism to other domains.

PMID- 27692210
TI  - Mechanistic explanation, cognitive systems demarcation, and extended cognition.
AB  - Approaches to the Internalism-Externalism controversy in the philosophy of mind
      often involve both (broadly) metaphysical and explanatory considerations. Whereas
      originally most emphasis seems to have been placed on metaphysical concerns,
      recently the explanation angle is getting more attention. Explanatory
      considerations promise to offer more neutral grounds for cognitive systems
      demarcation than (broadly) metaphysical ones. However, it has been argued that
      explanation-based approaches are incapable of determining the plausibility of
      internalist-based conceptions of cognition vis-a-vis externalist ones. On this
      perspective, improved metaphysics is the route along which to solve the
      Internalist-Externalist stalemate. In this paper we challenge this claim.
      Although we agree that explanation-orientated approaches have indeed so far
      failed to deliver solid means for cognitive system demarcation, we elaborate a
      more promising explanation-oriented framework to address this issue. We argue
      that the mutual manipulability account of constitutive relevance in mechanisms,
      extended with the criterion of 'fat-handedness', is capable of plausibly
      addressing the cognitive systems demarcation problem, and thus able to decide on
      the explanatory traction of Internalist vs. Externalist conceptions, on a case-by
      case basis. Our analysis also highlights why some other recent mechanistic takes
      on the problem of cognitive systems demarcation have been unsuccessful. We
      illustrate our claims with a case on gestures and learning.

PMID- 27692211
TI  - Kepler: Analogies in the search for the law of refraction.
AB  - This paper examines the methodology used by Kepler to discover a quantitative law
      of refraction. The aim is to argue that this methodology follows a heuristic
      method based on the following two Pythagorean principles: (1) sameness is made
      known by sameness, and (2) harmony arises from establishing a limit to what is
      unlimited. We will analyse some of the author's proposed analogies to find the
      aforementioned law and argue that the investigation's heuristic pursues such
      principles.

PMID- 27692212
TI  - Overlapping ontologies and Indigenous knowledge. From integration to ontological
      self-determination.
AB  - Current controversies about knowledge integration reflect conflicting ideas of
      what it means to "take Indigenous knowledge seriously". While there is increased
      interest in integrating Indigenous and Western scientific knowledge in various
      disciplines such as anthropology and ethnobiology, integration projects are often
      accused of recognizing Indigenous knowledge only insofar as it is useful for
      Western scientists. The aim of this article is to use tools from philosophy of
      science to develop a model of both successful integration and integration
      failures. On the one hand, I argue that cross-cultural recognition of property
      clusters leads to an ontological overlap that makes knowledge integration often
      epistemically productive and socially useful. On the other hand, I argue that
      knowledge integration is limited by ontological divergence. Adequate models of
      Indigenous knowledge will therefore have to take integration failures seriously
      and I argue that integration efforts need to be complemented by a political
      notion of ontological self-determination.

PMID- 27692213
TI  - Extensional scientific realism vs. intensional scientific realism.
AB  - Extensional scientific realism is the view that each believable scientific theory
      is supported by the unique first-order evidence for it and that if we want to
      believe that it is true, we should rely on its unique first-order evidence. In
      contrast, intensional scientific realism is the view that all believable
      scientific theories have a common feature and that we should rely on it to
      determine whether a theory is believable or not. Fitzpatrick argues that
      extensional realism is immune, while intensional realism is not, to the
      pessimistic induction. I reply that if extensional realism overcomes the
      pessimistic induction at all, that is because it implicitly relies on the
      theoretical resource of intensional realism. I also argue that extensional
      realism, by nature, cannot embed a criterion for distinguishing between
      believable and unbelievable theories.

PMID- 27692214
TI  - Carnap on unified science.
AB  - Unified science is a recurring theme in Carnap's work from the time of the Aufbau
      until the end of the 1930's. The theme is not constant, but knows several
      variations. I shall extract three quite precise formulations of the thesis of
      unified science from Carnap's work during this period: from the Aufbau, from
      Carnap's so-called syntactic period, and from Testability and Meaning and related
      papers. My main objective is to explain these formulations and to discuss their
      relation, both to each other and to other aspects of Carnap's work.

PMID- 27692215
TI  - Introduction: Testing philosophical theories.

PMID- 27692216
TI  - The re-emergence of hyphenated history-and-philosophy-of-science and the testing
      of theories of scientific change.
AB  - A basic premise of hyphenated history-and-philosophy-of-science is that theories
      of scientific change have to be based on empirical evidence derived from
      carefully constructed historical case studies. This paper analyses one such
      systematic attempt to test philosophical claims, describing its historical
      context, rationale, execution, and limited impact.

PMID- 27692217
TI  - The ontology of quantum field theory: Structural realism vindicated?
AB  - In this paper I elicit a prediction from structural realism and compare it, not
      to a historical case, but to a contemporary scientific theory. If structural
      realism is correct, then we should expect physics to develop theories that fail
      to provide an ontology of the sort sought by traditional realists. If structure
      alone is responsible for instrumental success, we should expect surplus ontology
      to be eliminated. Quantum field theory (QFT) provides the framework for some of
      the best confirmed theories in science, but debates over its ontology are vexed.
      Rather than taking a stand on these matters, the structural realist can embrace
      QFT as an example of just the kind of theory SR should lead us to expect. Yet, it
      is not clear that QFT meets the structuralist's positive expectation by providing
      a structure for the world. In particular, the problem of unitarily inequivalent
      representations threatens to undermine the possibility of QFT providing a unique
      structure for the world. In response to this problem, I suggest that the
      structuralist should endorse pluralism about structure.

PMID- 27692218
TI  - Looking forward, not back: Supporting structuralism in the present.
AB  - The view that the fundamental kind properties are intrinsic properties enjoys
      reflexive endorsement by most metaphysicians of science. But ontic structural
      realists deny that there are any fundamental intrinsic properties at all. Given
      that structuralists distrust intuition as a guide to truth, and given that we
      currently lack a fundamental physical theory that we could consult instead to
      order settle the issue, it might seem as if there is simply nowhere for this
      debate to go at present. However, I will argue that there exists an as-yet
      untapped resource for arguing for ontic structuralism - namely, the way that
      fundamentality is conceptualized in our most fundamental physical frameworks. By
      arguing that physical objects must be subject to the 'Goldilock's principle' if
      they are to count as fundamental at all, I argue that we can no longer view the
      majority of properties defining them as intrinsic. As such, ontic structural
      realism can be regarded as the most promising metaphysics for fundamental
      physics, and that this is so even though we do not yet claim to know precisely
      what that fundamental physics is.

PMID- 27692219
TI  - Structural realism versus deployment realism: A comparative evaluation.
AB  - In this paper I challenge and adjudicate between the two positions that have come
      to prominence in the scientific realism debate: deployment realism and structural
      realism. I discuss a set of cases from the history of celestial mechanics,
      including some of the most important successes in the history of science. To the
      surprise of the deployment realist, these are novel predictive successes toward
      which theoretical constituents that are now seen to be patently false were
      genuinely deployed. Exploring the implications for structural realism, I show
      that the need to accommodate these cases forces our notion of "structure" toward
      a dramatic depletion of logical content, threatening to render it explanatorily
      vacuous: the better structuralism fares against these historical examples, in
      terms of retention, the worse it fares in content and explanatory strength. I
      conclude by considering recent restrictions that serve to make "structure" more
      specific. I show however that these refinements will not suffice: the better
      structuralism fares in specificity and explanatory strength, the worse it fares
      against history. In light of these case studies, both deployment realism and
      structural realism are significantly threatened by the very historical challenge
      they were introduced to answer.

PMID- 27692220
TI  - A Modern Definition of the Athlete's Heart-for Research and the Clinic.
AB  - Exercise training can have a profound effect on cardiac structure. Recent
      evidence suggests that the greatest determinants of exercise-induced cardiac
      remodeling are the intensity, duration, and frequency of training. This also has
      overlap with athlete fitness. There are many additional factors that are
      important in determining cardiac remodeling, but while further refinements
      evolve, the authors argue that the best means of predicting the degree of
      expected physiologic remodeling is to either quantify training (intensity times
      total training time) or its by-product (exercise capacity). A uniform approach to
      estimating the degree of exercise-induced cardiac remodeling will enable more
      consistent research.

PMID- 27692221
TI  - Molecular Aspects of Exercise-induced Cardiac Remodeling.
AB  - Exercise-induced cardiac remodeling is typically an adaptive response associated
      with cardiac myocyte hypertrophy and renewal, increased cardiac myocyte
      contractility, sarcomeric remodeling, cell survival, metabolic and mitochondrial
      adaptations, electrical remodeling, and angiogenesis. Initiating stimuli/triggers
      of cardiac remodeling include increased hemodynamic load, increased sympathetic
      activity, and the release of hormones and growth factors. Prolonged and strenuous
      exercise may lead to maladaptive exercise-induced cardiac remodeling including
      cardiac dysfunction and arrhythmia. In addition, this article describes novel
      therapeutic approaches for the treatment of heart failure that target mechanisms
      responsible for adaptive exercise-induced cardiac remodeling, which are being
      developed and tested in preclinical models.

PMID- 27692222
TI  - Sudden Cardiac Death in Athletes: Still Much to Learn.
AB  - Athletes are often regarded as individuals at the pinnacle of health and fitness,
      nearly to the point of invincibility. The sudden cardiac death (SCD) of an
      athlete is therefore generally unexpected and extremely traumatic. Some of the
      most commonly identified causes of SCD in athletes include the genetic heart
      diseases. Despite thorough clinical and genetic investigation, in some cases a
      cause of death cannot be elucidated. Further research in these areas, spanning
      clinical, genetic, and public health perspectives, is required to help guide
      clinicians and those encountering the tragedy of SCD in an athlete.

PMID- 27692223
TI  - Using the 12-Lead Electrocardiogram in the Care of Athletic Patients.
AB  - This article summarizes the role of the 12-lead electrocardiogram (ECG) for the
      clinical care of athletes, with particular reference to the influence of age,
      gender, ethnicity, and type of sport on the appearance of the ECG, and its role
      in differentiating physiologic exercise-related changes from pathologic
      conditions implicated in sudden cardiac death (SCD). The article also explores
      the potential role of the ECG in detecting athletes at risk of SCD. In addition,
      the article reviews the evolution of ECG interpretation criteria and emphasizes
      the limitations of the ECG as well as the potential for future research.

PMID- 27692224
TI  - Exercise-Induced Atrial Remodeling: The Forgotten Chamber.
AB  - Cardiac changes in athletes involve the left ventricle and atrium. Mild left
      atrial enlargement is common among competitive athletes, possibly a physiologic
      adaptation to exercise conditioning. The prevalence of this remodeling and the
      association with supraventricular arrhythmias has not been systematically
      addressed. Echocardiography screens for patients with disease involving the left
      atrium. New techniques like speckle tracking can recognize early atrial
      dysfunction and assess left atrial myocardial function in patients with either
      physiologic or pathologic left ventricular hypertrophy. This article reviews
      echocardiographic techniques in delineating the athlete's morphology and
      functional properties of the left atrium.

PMID- 27692225
TI  - Atrial Fibrillation in Endurance Athletes: From Mechanism to Management.
AB  - Exercise training has considerable health benefits. However, recent research has
      demonstrated a greater risk of atrial arrhythmias in endurance athletes. The
      mechanisms promoting atrial fibrillation in athletes are unclear but there seems
      to be a central role for atrial remodeling, accompanied by autonomic alterations
      and inflammation. Animal studies have provided unique insights, yet prospective
      human data are lacking. Treatment options seem to yield similar efficacy to that
      seen in a nonathletic population and may be justified as an early rhythm control
      strategy. Further studies are required to enhance understanding of the cardiac
      adaptations to intensive exercise training.

PMID- 27692226
TI  - Congenital Heart Disease and the Athlete: What We Know and What We Do Not Know.
AB  - Since outcomes for patients with congenital heart disease (CHD) have greatly
      improved, most patients with CHD are surviving into adulthood and creating
      dilemmas for practitioners with regard to competitive sports participation. Much
      time, effort, and expertise have gone into developing the new American Heart
      Association/American College of Cardiology's guidelines and the European Society
      of Cardiology's guidelines. Practitioners should consult the guidelines but also
      be aware of gaps in the literature and should individualize recommendations for
      each patient. Both participation and restriction decisions should be made
      thoughtfully and collaboratively with athletes as either decision carries
      important consequences."

PMID- 27692227
TI  - Exercise Prescription for the Athlete with Cardiomyopathy.
AB  - Inherited cardiomyopathies have highly variable expression in terms of symptoms,
      functional limitations, and disease severity. Associated risk of sudden cardiac
      death is also variable. International guidelines currently recommend restriction
      of all athletes with cardiomyopathy from participation in competitive sports.
      While the guidelines are necessarily conservative because predictive risk factors
      for exercise-triggered SCD have not been clearly identified, the risk is clearly
      not uniform across all athletes and all sports. The advent of implantable
      cardioverter defibrillators, automated external defibrillators, and successful
      implementation of emergency action plans may safely mitigate risk of sudden
      cardiac death during physical activity. An individualized approach to risk
      stratification of athletes that recognizes patient autonomy may allow many
      individuals with cardiomyopathies to safely train and compete.

PMID- 27692228
TI  - Beyond the Bruce Protocol: Advanced Exercise Testing for the Sports Cardiologist.
AB  - Exercise testing is an important tool for determining baseline fitness as well as
      to diagnose limitations in performance. The Bruce protocol has become the
      standard for exercise testing protocol in many exercise physiology laboratories,
      but is rarely a suitable test for athletes who often have complex hemodynamic and
      metabolic demands during exercise required for practice and competition. We
      describe the approach for exercise testing beyond the Bruce protocol and focus on
      strategies to individualize the testing protocol to the metabolic demands of an
      athlete's sport.

PMID- 27692229
TI  - Sports Cardiology: Comprehensive Clinical Care for Athletes and Highly Active
      Individuals.

PMID- 27692230
TI  - Quick Tips for Getting Back to Peak Productivity.

PMID- 27692231
TI  - Shaping Variation in the Human Immune System.
AB  - Immune responses demonstrate a high level of intra-species variation,
      compensating for the specialization capacity of pathogens. The recent advent of
      in-depth immune phenotyping projects in large-scale cohorts has allowed a first
      look into the factors that shape the inter-individual diversity of the human
      immune system. Genetic approaches have identified genetic diversity as drivers of
      20-40% of the variation between the immune systems of individuals. The remaining
      60-80% is shaped by intrinsic factors, with age being the predominant factor, as
      well as by environmental influences, where cohabitation and chronic viral
      infections were identified as key mediators. We review and integrate the recent
      in-depth large-scale studies on human immune diversity and its potential impact
      on health. VIDEO ABSTRACT.

PMID- 27692232
TI  - Outcome After Rewarming From Accidental Hypothermia by Use of Extracorporeal
      Circulation.
AB  - BACKGROUND: Accidental hypothermia with arrested circulation remains a condition
      associated with high mortality. In our institution, extracorporeal circulation
      (ECC) rewarming has been the cornerstone in treating such patients since 1987. We
      here explore characteristics and outcomes of this treatment, to identify
      significant merits and challenges from 3 decades of experience in ECC rewarming.
      METHODS: Sixty-nine patients rewarmed by ECC during the period from December 1987
      to December 2015 were analyzed. One patient was excluded from the analyses
      because of combined traumatic cerebral injury. The analysis was focused on
      patient characteristics, treatment procedures, and outcomes were focused.
      Survivors were evaluated according to the cerebral performance categories scale.
      Simple statistics with nonparametric tests and chi2 tests were used. Median value
      and range are reported. RESULTS: Median age was 30 years (minimum 1.5, maximum
      76), and the cause of accidental hypothermia was cold exposure (27.9%), avalanche
      (5.9%), and immersion/submersion accidents (66.2%). Eighteen patients survived
      (26.5%). The survival rate did not improve during the years. Survivors had lower
      serum potassium (p = 0.002), higher pH (p = 0.03), lower core temperature (p =
      0.02), and shorter cardiopulmonary resuscitation time (p = 0.001), but ranges
      were wide. Although suspected primary hypoxia and hypothermia were associated
      with lower survival, we observed a 10.5% survival of these victims. Sixteen
      survivors had good outcome (cerebral performance category 1 or 2), whereas 2
      patients with suspected primary hypoxia survived with severe cerebral disability
      (cerebral performance category 3). CONCLUSIONS: Despite extended experience with
      ECC rewarming, improved handling strategies, and intensive care, no overall
      improvement in survival was observed. Good outcome was observed even among
      patients with a dismal prognosis.

PMID- 27692233
TI  - Long-Term Outcome of Patients With Complete Atrioventricular Septal Defect
      Combined With the Tetralogy of Fallot: Staged Repair Is Not Inferior to Primary
      Repair.
AB  - BACKGROUND: Primary repair is the preferred strategy for surgical treatment of
      complete atrioventricular septal defect combined with the tetralogy of Fallot.
      However, a staged approach may be preferable for very small or cyanotic infants.
      The long-term outcomes of infants undergoing staged vs primary repair were
      compared. METHODS: Data from 47 patients with complete atrioventricular septal
      defect combined with the tetralogy of Fallot who were operated on at our
      institution between 1974 and 2013 were reviewed. The study end points were all
      cause death and reoperation. The patients were classified into two groups: staged
      repair (SR) and primary repair (PR). The indications for staged repair were
      cyanosis and young age. RESULTS: There were 22 SR and 25 PR patients. The SR
      patients were younger at the time of the initial operation (p = 0.001), and were
      more frequently cyanotic (21 SR vs 5 PR patients, p = 0.003). The 10-year
      survival after repair of the SR and PR patients was 78% +/- 11% and 83% +/- 8%,
      respectively (p = 0.8). No risk factors for death were identified. The 10-year
      freedom from reoperation for atrioventricular valve regurgitation of SR and PR
      patients after repair was 73% +/- 12% and 71% +/- 10%, respectively (p = 0.5). At
      least moderate atrioventricular valve regurgitation before repair was the only
      risk factor for reoperation (p = 0.01). CONCLUSIONS: Cyanotic and very young
      children with complete atrioventricular septal defect combined with the tetralogy
      of Fallot who require urgent treatment have long-term outcomes after staged
      repair similar to those of patients who undergo primary repair. Preoperative
      atrioventricular valve regurgitation is associated with increased risk for
      reoperation over the long-term.

PMID- 27692235
TI  - [Cutaneous loxoscelism, about an exceptional observation of 9 consecutive cases].
AB  - INTRODUCTION: Loxosceles spiders are ubiquitous and responsible for many cases of
      envenomation in the world. The kind rufescens is present in the Provence and
      Occitan regions in France. During the summer 2015, we faced many Loxosceles
      rufescens cases of bites having led to extensive integumental necrosis whose
      features and singular evolution seems important to report. MATERIAL AND METHODS:
      We report the cases of nine patients who experienced a spider bite in the summer
      of 2015 in the Languedoc Roussillon. RESULTS: Of nine patients, eight patients
      had skin necrosis and five required surgical care. Five patients had a fever and
      had five other general signs such as important asthenia, joint pain, nausea and
      dizziness. CRP was very low normal in all patients. Finally, five of the nine
      patients reported a residual pain. DISCUSSION: L. rufescens is a small spider (7
      to 15mm in diameter) having a cytotoxic venom. Loxoscelism diagnosis is usually
      made by removing a front necrotic skin lesion. Of systemic loxoscelism that have
      been described, some American species had fatal outcomes. The treatment remains
      controversial with various options: surgery, antibiotics, antihistaminics,
      antivenom. CONCLUSION: The diagnosis must be made in endemic areas when
      confronted to a necrosic integumentary infectious rapidly progressive,
      unresponsive to antibiotic treatment associated with atypical general signs.

PMID- 27692234
TI  - NADPH-diaphorase reactivity and Fos-immunoreactivity within the ventral horn of
      the lumbar spinal cord of cats submitted to acute muscle inflammation induced by
      injection of carrageenan.
AB  - The NADPH-diaphorase activity and Fos-immunoreactivity within the ventral horn of
      the lumbar spinal cord were studied in cats with acute unilateral myositis
      following injection of carrageenan into the m.m. gastrocnemius-soleus. In
      carrageenan-injected cats maximum in the mean number of intensely stained NADPH
      diaphorase reactive (NADPH-dr) neurons was found in lamina VII (+100%) and VIII
      (+33%) of the contralateral ventral horn of the L6/L7 segments as compared with
      control animals. The maximumal level of Fos-immunoreactivity was registered in
      the same laminae with ipsilateral predominance (39.3+/-4.6 and 7.6+/-0.9 cells),
      in comparison with the contralateral side (13.6+/-0.8 and 5.5+/-0.6 cells,
      respectively; P<0.05). We also visualized low-intensely stained and double
      labelled (Fos immunoreactive+low-intensely stained NADPH-dr) multipolar and
      fusiform Renshaw-like cells (RLCs) within the ventral horn on both sides of the
      L6/L7 segments in carrageenan-injected cats. We visualized the double labelled
      (Fos-ir+NADPH-dr) multipolar and fusiform Renshaw-like cells (RLCs) within the
      ventral horn on both sides of the L6/L7 segments in carrageenan-injected cats. A
      significant difference in the mean number of RLCs was recorded between the ipsi-
      and contralateral sides in the lamina VII (13.6+/-2.5 vs. 4.9+/-0.7 cells,
      respectively). We suppose that activation of inhibitory RLCs in ipsilateral
      lamina VII could be directed on attenuation of activation of motoneurons during
      muscle pain development. Our study showed that a significant contralateral
      increase in the number of NADPH-dr cells is accompanied by an ipsilateral
      increase in c-Fos expression in lamina VII. These data may suggest that NADPH-dr
      neurons of the contralateral ventral horn through commissural connections also
      involved in the maintenance of the neuronal activity associated with acute muscle
      inflammation. It is also hypothesized, that during acute myositis, plastic
      changes in the ventral horn activate the processes of disinhibition due to an
      increase in the number of NADPH-d-reactive neurons in the spinal gray matter.

PMID- 27692236
TI  - [Palsy of the upper limb: Obstetrical brachial plexus palsy, arthrogryposis,
      cerebral palsy].
AB  - "Palsy of the upper limb" in children includes various diseases which leads to
      hypomobility of the member: cerebral palsy, arthrogryposis and obstetrical
      brachial plexus palsy. These pathologies which differ on brain damage or not,
      have the same consequences due to the early achievement: negligence, stiffness
      and deformities. Regular entire clinical examination of the member, an assessment
      of needs in daily life, knowledge of the social and family environment, are key
      points for management. In these pathologies, the rehabilitation is an emergency,
      which began at birth and intensively. Splints and physiotherapy are part of the
      treatment. Surgery may have a functional goal, hygienic or aesthetic in different
      situations. The main goals of surgery are to treat: joints stiffness, bones
      deformities, muscles contractures and spasticity, paresis, ligamentous laxity.

PMID- 27692239
TI  - Intestinal colonisation with extended-spectrum cephalosporin-resistant
      Escherichia coli in Swiss pets: molecular features, risk factors and transmission
      with owners.

PMID- 27692240
TI  - Susceptibility of periodontal pathogens to moxifloxacin: an in vitro study.

PMID- 27692237
TI  - An Ultraconserved Brain-Specific Enhancer Within ADGRL3 (LPHN3) Underpins
      Attention-Deficit/Hyperactivity Disorder Susceptibility.
AB  - BACKGROUND: Genetic factors predispose individuals to attention
      deficit/hyperactivity disorder (ADHD). Previous studies have reported linkage and
      association to ADHD of gene variants within ADGRL3. In this study, we
      functionally analyzed noncoding variants in this gene as likely pathological
      contributors. METHODS: In silico, in vitro, and in vivo approaches were used to
      identify and characterize evolutionary conserved elements within the ADGRL3
      linkage region (~207 Kb). Family-based genetic analyses of 838 individuals (372
      affected and 466 unaffected patients) identified ADHD-associated single
      nucleotide polymorphisms harbored in some of these conserved elements. Luciferase
      assays and zebrafish green fluorescent protein transgenesis tested conserved
      elements for transcriptional enhancer activity. Electromobility shift assays were
      used to verify transcription factor-binding disruption by ADHD risk alleles.
      RESULTS: An ultraconserved element was discovered (evolutionary conserved region
      47) that functions as a transcriptional enhancer. A three-variant ADHD risk
      haplotype in evolutionary conserved region 47, formed by rs17226398, rs56038622,
      and rs2271338, reduced enhancer activity by 40% in neuroblastoma and astrocytoma
      cells (pBonferroni < .0001). This enhancer also drove green fluorescent protein
      expression in the zebrafish brain in a tissue-specific manner, sharing aspects of
      endogenous ADGRL3 expression. The rs2271338 risk allele disrupts binding of YY1
      transcription factor, an important factor in the development and function of the
      central nervous system. Expression quantitative trait loci analysis of postmortem
      human brain tissues revealed an association between rs2271338 and reduced ADGRL3
      expression in the thalamus. CONCLUSIONS: These results uncover the first
      functional evidence of common noncoding variants with potential implications for
      the pathology of ADHD.

PMID- 27692241
TI  - Automated activity monitoring and visual observation of estrus in a herd of loose
      housed Hereford cattle: Diagnostic accuracy and time to ovulation.
AB  - A prospective cohort study was performed in the purebred Hereford herd at Gotala
      Beef and Lamb Research Centre, Sweden. The study's first objective was to assess
      the ability of an automatic activity monitoring system (AAMS) to detect estrus in
      beef suckler cows, and its second objective was to estimate the time from estrus
      to ovulation. The study sample (n = 38) consisted of 14 Hereford heifers and 24
      Hereford cows. Standardized visual observation of estrus was performed for 20
      minutes thrice daily, and animal activity was recorded with an AAMS system,
      Heatime (SCR Engineers Ltd., Israel). Cows in estrus underwent transrectal
      ultrasonography every 8 hours, to estimate the time of ovulation. Blood samples
      for progesterone analysis were collected thrice weekly throughout the study
      period. A cutoff value of 1-ng progesterone/mL of serum was used to define luteal
      activity. The AAMS had a 90% (95% confidence interval [CI] 77%-97%) sensitivity
      and 100% specificity (95% CI 94%-100%), and visual detection of estrus had a 77%
      sensitivity (95% CI 62%-88%) and a 89% specificity (95% CI 79%-95%) for
      identifying estrus when compared to the gold standard defined by temporal pattern
      of serum progesterone concentration. When both methods were used in parallel, the
      sensitivity increased to 96% (95% CI 86%-99%), and the specificity increased to
      90% (95% CI 80%-96%). The time of ovulation after estrus was determined on 50
      occasions. The median estrus (AAMS detected) to ovulation interval was 25 hours
      for heifers and 23 hours for cows (interquartile range 11-29 hours and 19-25
      hours, respectively). The median estrus (visually detected) to ovulation interval
      was 28 hours for heifers and 21 hours for cows (interquartile range 13-29 hours
      for both categories). In conclusion, the AAMS had both a higher sensitivity and
      specificity for estrus detection than thrice-daily visual observation. The time
      from detection of estrus to ovulation observed in this study indicates that
      reproductive performance might be improved if Hereford cattle are inseminated
      sooner after detection of estrus than is currently recommended.

PMID- 27692238
TI  - Heterogeneity in Dopamine Neuron Synaptic Actions Across the Striatum and Its
      Relevance for Schizophrenia.
AB  - Brain imaging has revealed alterations in dopamine uptake, release, and receptor
      levels in patients with schizophrenia that have been resolved on the scale of
      striatal subregions. However, the underlying synaptic mechanisms are on a finer
      scale. Dopamine neuron synaptic actions vary across the striatum, involving
      variations not only in dopamine release but also in dopamine neuron connectivity,
      cotransmission, modulation, and activity. Optogenetic studies have revealed that
      dopamine neurons release dopamine in a synaptic signal mode, and that the neurons
      also release glutamate and gamma-aminobutyric acid as cotransmitters, with
      striking regional variation. Fast glutamate and gamma-aminobutyric acid
      cotransmission convey discrete patterns of dopamine neuron activity to striatal
      neurons. Glutamate may function not only in a signaling role at a subset of
      dopamine neuron synapses, but also in mediating vesicular synergy, contributing
      to regional differences in loading of dopamine into synaptic vesicles. Regional
      differences in dopamine neuron signaling are likely to be differentially involved
      in the schizophrenia disease process and likely determine the subregional
      specificity of the action of psychostimulants that exacerbate the disorder, and
      antipsychotics that ameliorate the disorder. Elucidating dopamine neuron synaptic
      signaling offers the potential for achieving greater pharmacological specificity
      through intersectional pharmacological actions targeting subsets of dopamine
      neuron synapses.

PMID- 27692242
TI  - Editorial for the Special Issue on MICCAI 2015.

PMID- 27692243
TI  - The relation of saturated fatty acids with low-grade inflammation and
      cardiovascular disease.
AB  - The mantra that dietary (saturated) fat must be minimized to reduce
      cardiovascular disease (CVD) risk has dominated nutritional guidelines for
      decades. Parallel to decreasing intakes of fat and saturated fatty acids (SFA),
      there have been increases in carbohydrate and sugar intakes, overweight, obesity
      and type 2 diabetes mellitus. The "lipid hypothesis" coined the concept that fat,
      especially SFA, raises blood low-density lipoprotein-cholesterol and thereby CVD
      risk. In view of current controversies regarding their adequate intakes and
      effects, this review aims to summarize research regarding this heterogenic group
      of fatty acids and the mechanisms relating them to (chronic) systemic low-grade
      inflammation, insulin resistance, metabolic syndrome and notably CVD. The
      intimate relationship between inflammation and metabolism, including glucose, fat
      and cholesterol metabolism, revealed that the dyslipidemia in Western societies,
      notably increased triglycerides, "small dense" low-density lipoprotein and
      "dysfunctional" high-density lipoprotein, is influenced by many unfavorable
      lifestyle factors. Dietary SFA is only one of these, not necessarily the most
      important, in healthy, insulin-sensitive people. The environment provides us not
      only with many other proinflammatory stimuli than SFA but also with many
      antiinflammatory counterparts. Resolution of the conflict between our self
      designed environment and ancient genome may rather rely on returning to the
      proinflammatory/antiinflammatory balance of the Paleolithic era in consonance
      with the 21st century culture. Accordingly, dietary guidelines might reconsider
      recommendations for SFA replacement and investigate diet in a broader context,
      together with nondietary lifestyle factors. This should be a clear priority,
      opposed to the reductionist approach of studying the effects of single nutrients,
      such as SFA.

PMID- 27692244
TI  - Corrigendum to "Dietary interesterified fat enriched with palmitic acid induces
      atherosclerosis by impairing macrophage cholesterol efflux and eliciting
      inflammation" [J Nutr Biochem 32C (2016) 91-100].

PMID- 27692245
TI  - Is Bladder Training by Clamping Before Removal Necessary for Short-Term
      Indwelling Urinary Catheter Inpatient? A Systematic Review and Meta-analysis.
AB  - PURPOSE: Urinary catheterization is a common technique in clinical practice.
      There is, however, no consensus on management prior to removal of the indwelling
      catheter for short-term patients. This systematic review examined the necessity
      of clamping before removal of an indwelling urinary catheter in short-term
      patients. METHODS: A systematic literature review was conducted using eight
      databases and predetermined keywords-guided searches. Some 2,515 studies were
      evaluated. Ten studies that met the inclusion criteria were selected. RESULTS:
      The quality of the studies was assessed using the Jadad scoring system. Only
      40.0% of studies were rated as high quality. This review found that catheter
      clamping prior to removal was not necessary for the short-term patient. When made
      a comparison with the unclamping group, there was no significant difference in
      recatheterization risk, risk of urine retention, patients' subjective perceptions
      and rate of urinary tract infection. CONCLUSIONS: This review indicated that
      bladder training by clamping prior to removal of urinary catheters is not
      necessary in short-term catheter patients. In addition, clamping carries the risk
      of complications such as prolonging urinary catheter retention and urinary tract
      injury. Further investigation requires higher quality methodologies and more
      diverse study designs.

PMID- 27692246
TI  - Structural Equation Modeling to Assess Discrimination, Stress, Social Support,
      and Depression among the Elderly Women in South Korea.
AB  - PURPOSE: The purpose of this study was to find the relationship and conceptual
      model of discrimination, stress, support, and depression among the elderly in
      South Korea. METHODS: This was a cross-sectional descriptive study involving 207
      community-dwelling elders. Data were collected through questionnaires from May 5
      to May 31, 2014 in community senior centers, and analyzed using descriptive
      statistics, t test, analysis of variance, Scheffe test, and structural equation
      modeling. RESULTS: There were significant effects of discrimination on stress,
      support on stress and stress on depression. Moreover, there were two significant
      indirect effects observed between discrimination and depression, and between
      support and depression. For each indirect effect, the mediating factor was
      stress. Additionally, there was no direct effect between discrimination and
      depression or support. CONCLUSIONS: This study found that social support and
      discrimination had indirect effects on depression through stress. More
      specifically, decreased stress led to a reduction of depression. Therefore,
      social support based on a thorough understanding of stress is very important for
      caring elderly who are depressive.

PMID- 27692247
TI  - Influencing Factors of Intention to Receive Pap Tests in Vietnamese Women who
      Immigrated to Taiwan for Marriage.
AB  - PURPOSE: This study aimed to explore the factors associated with the intention to
      receive a Pap test among married immigrant women of Vietnamese origin living in
      Taiwan. METHODS: This was a cross-sectional community-based study. We enrolled
      281 women aged 30 years and over in the study, from July 2013 to January 2014.
      The participants' characteristics, cervical cancer knowledge, Pap test knowledge,
      attitudes toward cervical cancer, barriers to receiving a Pap test, fatalism, and
      intention to receive a Pap test, were measured using self-report questionnaires.
      Hierarchical multiple regression analyses were performed to examine the variables
      associated with participants' intentions to receive a Pap test. RESULTS:
      Vietnamese women with low scores on the measures of cervical cancer knowledge and
      perceived barriers to receiving a Pap test were more willing to receive the test,
      as were those with high scores on the measures of Pap test knowledge and
      fatalism. Women who received a Pap test in the previous year were more willing to
      receive a Pap test within the next 3 years. CONCLUSIONS: Preventive healthcare
      for immigrant women should be a focus of nurses. The development of culturally
      appropriate health education and strategies should enhance their knowledge of Pap
      tests and reduce perceived barriers to Pap test participation. This study's
      results can be a reference for nurses who work with immigrant women.

PMID- 27692248
TI  - Psychometric Evaluation of a Turkish Version of the Diabetes Fear of Self
      injecting and Self-testing Questionnaire (D-FISQ).
AB  - PURPOSE: To examine the psychometric properties of a Turkish version of the
      Diabetes Fear of Injecting and Self-testing Questionnaire (D-FISQ). METHODS:
      Forward-backward translation of the D-FISQ from English into Turkish was
      conducted. Original English and translated forms were examined by a panel group.
      Validity was investigated using content, confirmatory factor analysis, and
      divergent validity. Reliability was assessed using Cronbach alpha values, item
      total correlations, and intraclass correlations. The sample comprised 350
      patients with diabetes. Data were analyzed using SPSS 15.0 for Windows and LISREL
      8. RESULTS: The content validity index for the panel members was .90, which
      indicated perfect content validity; items in D-FISQ were clear, concise,
      readable, and distinct. Confirmatory factor analysis confirmed the original
      construct of the D-FISQ. All items had factor loadings higher than the
      recommended level of .40. The D-FISQ scores were discriminated by the level of
      anxiety. Reliability results were also satisfactory. Cronbach alpha values were
      within ideal limits. Item-total correlation coefficient ranged from .72 to .86.
      In terms of test-retest reliability, intraclass correlation coefficient was found
      to be over .90. CONCLUSIONS: D-FISQ is a valid and reliable questionnaire in
      assessing needle-prick fear among Turkish patients with diabetes. We recommend
      performing the Turkish D-FISQ in determining and screening patients with diabetes
      who have fear related to self-insulin injection and finger-prick test. Thus,
      health care professionals should be aware of the potential consequences of
      injection fear such as insulin misuse and poor self-monitoring of blood glucose,
      which may have unfavorable effects on optimal diabetes management.

PMID- 27692249
TI  - Other Side of Breast Cancer: Factors Associated with Caregiver Burden.
AB  - PURPOSE: This study aimed to determine factors associated with caregiver burden
      among primary caregivers of women with breast cancer in Iran. METHODS: This was a
      descriptive correlation study conducted in 2012 on 150 main caregivers of
      patients with breast cancer who came to the oncology clinic of Shahid Ghazi
      hospital in Tabriz, Iran. A questionnaire which included caregiving-related
      factors and the Zarit Burden Interview was used for data collection after its
      validity and reliability were determined. Data was analyzed using SPSS 13.0
      software with descriptive and analytic statistics. The association between
      significant variables and the dependent variable with an observation of the
      effects of other variables was assessed using the multiple linear regression
      model. RESULTS: The mean age of caregivers was 39.60 +/- 13.80 years old, and 77
      (51.3%) of them were men. The mean score of the Zarit Burden Interview was 30.55
      +/- 19.18. In the regression model, the mean score of activities of daily living,
      level of education, gender, and financial status were identified as the
      determining factors of the burden of caregivers. CONCLUSIONS: Primary caregivers
      need to be financially supported by the relevant organizations. Care skills
      training and providing palliative care seem helpful in reducing the pain and the
      burden of family caregivers for patients with breast cancer.

PMID- 27692250
TI  - Psychometric Properties of Korean Version of Self-Efficacy of Evidence-Based
      Practice Scale.
AB  - PURPOSE: This study is to evaluate the psychometric properties of the Korean
      version of the Self-Efficacy of Evidence-Based Practice (SE-EBP) scale, which was
      originally developed by Chang and Crowe. The beta-version of the SE-EBP is a
      modified version of the original SE-EBP, which measures the clinical nurses'
      confidence in finding, appraising, and implementing evidence into practice.
      Although the original SE-EBP has been validated, no study has been conducted to
      validate the Korean version of SE-EBP. METHODS: The original scale was translated
      into Korean through a process of forward and back translation of the original
      scale. After getting confirmation of the equivalence of the Korean forward
      translation by the original author, exploratory factor analysis and confirmatory
      factor analysis of data from 212 clinical nurses were used to test construct
      validity. Internal consistency was examined using Cronbach alpha coefficients.
      For the statistical analysis, STATA version 13.0 software program was used.
      RESULTS: Exploratory factor analysis of the 28 items revealed three factors with
      eigenvalues above 1, accounting for 60.2% of the total variance. Confirmatory
      factor analysis showed good fit of the three-factor structure which was
      statistically significant (chi2=718.61, df=330, p<.01). For internal consistency,
      Cronbach alpha coefficient for the total scale was .95, and it was greater than
      .80 for each of the three subscales. CONCLUSIONS: The Korean version of SE-EBP
      scale showed evidence of adequate construct validity and reliability. This study
      might have contributed to a wider application of the SE-EBP scale, but further
      studies are needed to provide more evidence on the structure of the scale.

PMID- 27692251
TI  - A Predictive Model of Domestic Violence in Multicultural Families Focusing on
      Perpetrator.
AB  - PURPOSE: This study was conducted to assess predictor variables of husbands in
      multicultural families and examine the relationship among variables after setting
      up a hypothetical model including influencing factors, so as to provide a
      framework necessary for developing nursing interventions of domestic violence.
      METHODS: The participants were 260 husbands in multicultural families in four
      cities in Korea. Data were analyzed using SPSS 22.0 and AMOS 20.0. RESULTS: Self
      control, social support, family of origin violence experience and stress on
      cultural adaptation directly affected to dysfunctional communication, and the
      explanatory power of the variables was 64.7%. Family of origin violence
      experience in domestic stress on cultural adaptation, and dysfunctional
      communication were directly related to domestic violence in multicultural
      families, and the explanatory power of the variables was 64.6%. We found out that
      all variables in the model had mediation effects to domestic violence through
      dysfunctional communication. In other words, self-control and social support had
      complete mediation effects, and family of origin violence experience in domestic
      violence and stress on cultural adaptation had partial mediation effects.
      CONCLUSIONS: The variables explained in this study should be considered as
      predictive factors of domestic violence in multicultural families, and used to
      provide preventive nursing intervention. Our resutls can be taken into account
      for developing and implementing programs on alleviating dysfunctional
      communication in multicultural families in Korea.

PMID- 27692252
TI  - Why Women Living in an Obstetric Care Underserved Area Do Not Utilize Their Local
      Hospital Supported by Korean Government for Childbirth.
AB  - PURPOSE: This study aimed to understand why mothers do not utilize the prenatal
      care and delivery services at their local hospital supported by the government
      program, the Supporting Program for Obstetric Care Underserved Area (SPOU).
      METHODS: We conducted a focus group interview by recruiting four mothers who
      delivered in the hospital in their community (a rural underserved obstetric care
      area) and another four mothers who delivered in the hospital outside of the
      community. RESULTS: From the finding, the mothers were not satisfied with the
      quality of services that the community hospital provided, in terms of
      professionalism of the obstetric care team, and the outdated medical device and
      facilities. Also, the mothers believed that the hospital in the metropolitan city
      is better for their health as well as that of their babies. The mothers who
      delivered in the outside community hospital considered geographical closeness
      less than they did the quality of obstetric care. The mothers who delivered in
      the community hospital gave the reason why they chose the hospital, which was
      convenience and emergency preparedness due to its geographical closeness.
      However, they were not satisfied with the quality of services provided by the
      community hospital like the other mothers who delivered in the hospital outside
      of the community. CONCLUSIONS: Therefore, in order to successfully deliver the
      SPOU program, the Korean government should make an effort in increasing the
      quality of maternity service provided in the community hospital and improving the
      physical factors of a community hospital such as outdated medical equipment and
      facilities.

PMID- 27692253
TI  - Role of Emotional Intelligence in Conflict Management Strategies of Nurses.
AB  - PURPOSE: This study analyzes the emotional intelligence levels and conflict
      management strategies of nurses and the association between them. METHODS: This
      cross-sectional, descriptive study was conducted with 277 nurses in a stratified
      random sample from a university hospital in Turkey. The data were collected from
      nurses who gave their informed consent to participate using a personal
      information form, the Rahim Organizational Conflict Inventory-II and Bar-On's
      Emotional Quotient Inventory (EQ-I). Data were assessed by descriptive
      statistics, t tests, and Pearson correlation analyses, using SPSS software.
      RESULTS: The levels of the nurses' strategies were as follows: avoiding (M =
      2.98), dominating (M = 2.76), and obliging (M = 2.71) were medium; compromising
      (M = 1.99) and integration (M = 1.96) were low. The levels of the emotional
      intelligence of nurses (mean = 2.75) were medium on a 5-point scale. Integration
      (r = .168), obliging (r = .25), dominating (r = .18), and compromising (r = .33),
      which are conflict management strategies, were positively correlated with scores
      of emotional intelligence, and avoiding (r = -.25) was negatively correlated with
      scores of emotional intelligence (p < .05). CONCLUSIONS: The study determined
      that nurses' emotional intelligence affects conflict management strategies. To
      use effective strategies in conflict management, nurses must develop emotional
      intelligence. Training programs on conflict management and emotional intelligence
      are needed to improve effective conflict management in healthcare facilities.

PMID- 27692254
TI  - Relationship between Organizational Culture and Workplace Bullying among Korean
      Nurses.
AB  - PURPOSE: To identify the relationship between organizational culture and
      experience of workplace bullying among Korean nurses. METHODS: Participants were
      298 hospital nurses in Busan, South Korea. We assessed nursing organizational
      culture and workplace bullying among nurses using structured questionnaires from
      July 1 through August 15, 2014. RESULTS: Most participants considered their
      organizational culture as hierarchy-oriented (45.5%), followed by relation
      oriented (36.0%), innovation-oriented (10.4%), and task-oriented (8.1%).
      According to the operational bullying criteria, the prevalence of workplace
      bullying was 15.8%. A multivariate logistic regression analysis revealed that the
      odds of being a victim of bullying were 2.58 times as high among nurses in a
      hierarchy-oriented culture as among nurses in a relation-oriented culture [95%
      confidence interval (1.12, 5.94)]. CONCLUSIONS: The results suggest that the
      types of nursing organizational culture are related to workplace bullying in
      Korean nurses. Further research is needed to develop interventions that can
      foster relation-oriented cultures to prevent workplace bullying in nurses.

PMID- 27692255
TI  - Validation of Sinhala Version of Cardiff Wound Impact Schedule in Patients with
      Diabetic Leg and Foot Ulcers.
AB  - PURPOSE: To validate the Cardiff Wound Impact Schedule (CWIS) to assess the
      health-related quality of life (HRQoL) of Sri Lankan patients with diabetic leg
      and foot ulcers. METHODS: English version of CWIS was examined for cultural
      compatibility, translated into Sinhala and pretested. The Sinhala version was
      administered in parallel with the validated Sinhala version of SF-36 by an
      interviewer to all patients (n = 140) at baseline to determine the construct
      validity. Reliability of CWIS was measured by internal consistency and test
      retest stability. The instrument was readministered in 2 weeks on 33 patients
      with nonhealing ulcers to determine the test-retest stability and in 3 months on
      50 patients with healed ulcers to determine the ability of CWIS to discriminate
      HRQoL between patients with healed versus nonhealed ulcers. Acceptability of CWIS
      was assessed by the response rate, completion rate and the average time taken to
      complete a single interview. RESULTS: The construct validity demonstrated
      moderately significant correlations between related subscales of CWIS and SF-36
      (Spearman's r = .32-.51, p = .021 to p < .001) for the whole study sample.
      Internal consistencies (Cronbach alpha = .68-.86) and test-retest stability (.56
      .70) were acceptable. The tool was sensitive in discriminating the impact of the
      wound on HRQoL in healed versus nonhealed status (p <= .001). The tool showed
      good acceptability. CONCLUSIONS: The Sinhala version of CWIS is valid, reliable
      and acceptable for assessing the impact of wound on HRQoL. This instrument is
      sensitive in detecting the differences of the impact of healed and nonhealed
      ulcers on QoL in patients with diabetic leg and foot ulcer.

PMID- 27692256
TI  - Analysis of Workplace Health Education Performed by Occupational Health Managers
      in Korea.
AB  - PURPOSE: To evaluate workplace health education as practiced by occupational
      health managers based on standardized job tasks and suggest priority tasks and
      areas to be trained. METHODS: The study was conducted between November 10, 2013
      and April 30, 2014. The tool used in this study was standardized job tasks of
      workplace health education for occupational health managers which was developed
      through methodological steps. It was evaluated by 233 worksite occupational
      health managers. Data were analyzed using SPSS 21.0. RESULTS: Predicting
      variables of workplace health education performance were the "analysis and
      planning" factor, type of enterprise, and form of management. Healthcare
      professionals and occupational health managers who managed the nonmanufacturing
      industry showed high importance and low performance level in "analysis and
      planning" factor. CONCLUSIONS: "Analysis and planning" skill is priority training
      area for healthcare professionals and occupational health managers who managed
      nonmanufacturing industry. It is necessary to develop a training curriculum for
      occupational health managers that include improving analysis of worksites and
      plans for a health education program.

PMID- 27692257
TI  - Back of the net.

PMID- 27692258
TI  - Access to psychotropic medicines in low-resource settings.

PMID- 27692259
TI  - Translating neuroscience to the front lines: point-of-care detection of
      neuropsychiatric disorders.

PMID- 27692260
TI  - Kings College Hospital Trust v C: using and weighing information to assess
      capacity.

PMID- 27692261
TI  - Corrections.

PMID- 27692262
TI  - Network meta-analyses and treatment recommendations for obsessive-compulsive
      disorder.

PMID- 27692263
TI  - Network meta-analyses and treatment recommendations for obsessive-compulsive
      disorder.

PMID- 27692264
TI  - Network meta-analyses and treatment recommendations for obsessive-compulsive
      disorder - Authors' reply.

PMID- 27692266
TI  - Marta Rondon: champion for women's mental health in Peru.

PMID- 27692267
TI  - Was addiction psychiatry an accident of history?

PMID- 27692268
TI  - A warning to the curious.

PMID- 27692269
TI  - Data science for mental health: a UK perspective on a global challenge.
AB  - Data science uses computer science and statistics to extract new knowledge from
      high-dimensional datasets (ie, those with many different variables and data
      types). Mental health research, diagnosis, and treatment could benefit from data
      science that uses cohort studies, genomics, and routine health-care and
      administrative data. The UK is well placed to trial these approaches through
      robust NHS-linked data science projects, such as the UK Biobank, Generation
      Scotland, and the Clinical Record Interactive Search (CRIS) programme. Data
      science has great potential as a low-cost, high-return catalyst for improved
      mental health recognition, understanding, support, and outcomes. Lessons learnt
      from such studies could have global implications.

PMID- 27692270
TI  - Increased severity of sleep-disordered breathing is associated with insomnia and
      excessive somnolence in primary school children.
AB  - OBJECTIVE: The aim of the study was to investigate the prevalence of difficulty
      with initiation or maintenance of sleep (DIMS) and excessive daytime sleepiness
      (EDS) in a general pediatric population, and to evaluate the relationship between
      these conditions and sleep-disordered breathing (SDB) symptom intensity. METHODS:
      This population-based cross-sectional study from 27 primary schools in a medium
      sized city in Poland was based on use of a questionnaire regarding demographic
      data, symptoms of SDB, DIMS, and EDS. Data were collected between September and
      December 2014. In all, 2940 caregivers were recruited and were asked to fill-out
      questionnaires and written consent. RESULTS: A total of 68% of the questionnaires
      (n = 1987) were returned and analyzed. Habitual snoring (HS) was reported in 104
      (5.3%) children. DIMS and EDS were seen in 137 children (6.9%) and 117 children
      (5.9%), respectively. The prevalence of DIMS increased from 3.5% in children who
      never snored to 28.6% in children who snored very often or always. Similarly, the
      prevalence of EDS was 2.7% in children who did not snore and increased to 19% in
      children who snored very often or always. No correlation was seen between
      increasing DIMS (r = 0.006, p > 0.05) or EDS (r = -0.031, p > 0.05) scores and
      body mass index. CONCLUSIONS: This study is the first to measure the symptoms of
      both DIMS and EDS in a general pediatric population and to assess the
      relationship between both DIMS and EDS and SDB in children. We found that
      children with more frequent snoring had a higher prevalence of DIMS as well as
      EDS; however, there was no correlation between body mass index and either DIMS or
      EDS symptom severity.

PMID- 27692271
TI  - Daytime napping and increased risk of incident respiratory diseases: symptom,
      marker, or risk factor?
AB  - BACKGROUND: We have identified a strong association between daytime napping and
      increased mortality risk from respiratory diseases, but little is known about the
      relationship between daytime napping and respiratory morbidity. METHODS: Data
      were drawn from the European Prospective Investigation into Cancer and Nutrition
      Norfolk cohort. Participants reported napping habits during 1998-2000 and were
      followed up for respiratory disease hospital admissions until March 2009. Cox
      proportional hazards regression was used to examine the association between
      daytime napping and respiratory disease incidence risk. RESULTS: The study sample
      included 10,978 men and women with a mean age of 61.9 years, and a total of 946
      incident respiratory disease cases were recorded. After adjustment for age, sex,
      social class, education, marital status, employment status, nightshift work, body
      mass index, physical activity, smoking, alcohol intake, self-reported general
      health, hypnotic drug use, habitual sleep duration, and preexisting health
      conditions, daytime napping was associated with an increase in the overall
      respiratory disease incidence risk (hazard ratio (HR) = 1.32, 95% confidence
      interval (CI) 1.15, 1.52 for napping <1 h; HR = 1.54, 95% CI 1.14, 2.09 for
      napping >=1 h). This association was more pronounced for lower respiratory
      diseases, especially for the risk of chronic lower respiratory diseases (HR =
      1.52, 95% CI: 1.18, 1.96 for napping <1 h; HR = 1.72, 95% CI: 1.01, 2.92 for
      napping >=1 h, overall p = 0.003). CONCLUSIONS: Excessive daytime napping might
      be a useful marker of future respiratory disease incidence risk. Further studies
      are required to confirm these findings and help understand potential mechanisms.

PMID- 27692272
TI  - Hyperarousal in insomnia and hypnotic dose escalation.
AB  - BACKGROUND: Given concerns about the abuse liability of hypnotics, this study
      assessed hyperarousal in people with insomnia and its relation to hypnotic self
      administration over 12 months of nightly hypnotic use. METHODS: Ninety-five
      subjects with insomnia (age 32-64 years) underwent screening nocturnal
      polysomnogram (NPSG) and Multiple Sleep Latency Test (MSLT) the following day
      and, then, were randomized to receive zolpidem 10 mg or placebo nightly for 12
      months. NPSGs and MSLTs were conducted and urine was collected (0700-1500 h) and
      analyzed for norepinephrine (NE) levels during months one and eight on study
      medication. A subset (n = 54) underwent hypnotic self-administration assessments
      in months one, four, and 12. RESULTS: Mean daily sleep latency on screening MSLT
      was distributed across the full range of MSLT latencies (2-20 min). The highest
      screening MSLT latencies were detected in subjects with higher NE levels,
      compared to those with the lowest MSLT latencies. In the subset undergoing self
      administration assessment, those with the highest MSLT latencies chose more
      capsules (placebo and zolpidem) and increased the number of capsules chosen in
      months four relative to month one, compared to those with the lowest MSLT
      latencies. CONCLUSIONS: These data show that some insomniacs are hyperaroused
      with high MSLT/NE levels and, compared to low MSLT/NE insomniacs, they increase
      the number of capsules (zolpidem and placebo) self-administered on months four
      and 12 relative to Month one.

PMID- 27692273
TI  - Abnormal thyroid hormones and non-thyroidal illness syndrome in obstructive sleep
      apnea, and effects of CPAP treatment.
AB  - OBJECTIVE: In obstructive sleep apnea (OSA), while both hypothyroidism and
      hyperthyroidism have been studied, the occurrence of non-thyroidal illness
      syndrome (NTIS) (normal thyroid stimulating hormone [TSH] with low
      triiodotironine) has not been investigated. We explored the occurrence of NTIS in
      patients with moderate to severe OSA and its relationship to the severity of
      nocturnal respiratory disorders. We also studied the occurrence of subclinical
      hypothyroidism (SH, ie, high TSH with normal thyroxine) in OSA and changes in
      circulating TSH, free triiodotironine (fT3) and free thyroxine (fT4) after CPAP
      treatment. METHODS: After a nocturnal respiratory polysomnography, 125
      consecutive patients with moderate to severe OSA and 60 control subjects with
      normal nocturnal respiration were recruited. Morning circulating TSH, fT3, and
      fT4 were measured in all subjects. In a subsample of patients, nocturnal
      polysomnography and hormonal determinations were repeated after CPAP treatment
      for five months. RESULTS: NTIS was found in 13 (10.4%), and SH in ten (8%) OSA
      subjects, but not in any control subjects. Patients with NTIS showed worse mean
      nocturnal oxygen saturation and time with saturation <90% (both p < 0.001). After
      treatment, NTIS subjects (n = 13) showed an increase in fT3 (p < 0.001) to the
      normal range, and SH subjects (n = 6) a slight decrease in TSH (p = 0.01). In the
      patients with normal hormones before treatment (n = 45), no change was observed.
      CONCLUSIONS: NTIS may occur in OSA patients with severe nocturnal hypoxemia. OSA
      treatment is followed by an improvement in TSH in patients with abnormal baseline
      levels of this hormone, and by recovery of NTIS.

PMID- 27692274
TI  - Sleep characteristics in type 1 diabetes and associations with glycemic control:
      systematic review and meta-analysis.
AB  - OBJECTIVES: The association between inadequate sleep and type 2 diabetes has
      garnered much attention, but little is known about sleep and type 1 diabetes
      (T1D). Our objectives were to conduct a systematic review and meta-analysis
      comparing sleep in persons with and without T1D, and to explore relationships
      between sleep and glycemic control in T1D. METHODS: Studies were identified from
      Medline and Scopus. Studies reporting measures of sleep in T1D patients and
      controls, and/or associations between sleep and glycemic control, were selected.
      RESULTS: A total of 22 studies were eligible for the meta-analysis. Children with
      T1D had shorter sleep duration (mean difference [MD] = -26.4 minutes; 95%
      confidence interval [CI] = -35.4, -17.7) than controls. Adults with T1D reported
      poorer sleep quality (MD in standardized sleep quality score = 0.51; 95% CI =
      0.33, 0.70), with higher scores reflecting worse sleep quality) than controls,
      but there was no difference in self-reported sleep duration. Adults with TID who
      reported sleeping >6 hours had lower hemoglobin A1c (HbA1c) levels than those
      sleeping <=6 hours (MD = -0.24%; 95% CI = -0.47, -0.02), and participants
      reporting good sleep quality had lower HbA1c than those with poor sleep quality
      (MD = -0.19%; 95% CI = -0.30, -0.08). The estimated prevalence of obstructive
      sleep apnea (OSA) in adults with TID was 51.9% (95% CI = 31.2, 72.6). Patients
      with moderate-to-severe OSA had a trend toward higher HbA1c (MD = 0.39%, 95% CI =
      -0.08, 0.87). CONCLUSION: T1D was associated with poorer sleep and high
      prevalence of OSA. Poor sleep quality, shorter sleep duration, and OSA were
      associated with suboptimal glycemic control in T1D patients.

PMID- 27692275
TI  - Video-polysomnographic documentation of non-rapid eye movement sleep parasomnia
      followed by rapid eye movement sleep behavior disorder: a parasomnia overlap
      disorder?

PMID- 27692276
TI  - Emotional availability at bedtime, infant temperament, and infant sleep
      development from one to six months.
AB  - Infant sleep consolidates rapidly during the first half year of life in the
      context of a dynamic, bidirectional exchange between infant characteristics and
      the caregiving environment. The current study examined the relationship between
      mothers' emotional availability (EA) at bedtime and infant temperament, and
      objectively assessing infant sleep development from one to six months,
      particularly focus on whether infant temperament moderated linkages between EA at
      bedtime and infant sleep development. The sample consisted of 72 mother-infant
      dyads, and the measures included actigraphy-assessed infant sleep at one and six
      months, observed maternal EA coded from bedtime videos at 3 and 6 months, and
      maternal reports of infant temperament at three and six months. The analysis
      showed significant positive effects of maternal EA at bedtime on developmental
      changes in infant sleep minutes. Additionally, infant temperamental surgency
      moderated the influence of EA at bedtime on the increase in infant sleep minutes.
      In other words, highly surgent infants whose mothers were emotionally available
      at bedtime showed a greater increase in their sleep time than other infants. The
      results are discussed in terms of the transactional model of infant sleep
      development.

PMID- 27692277
TI  - Sleep and melatonin secretion abnormalities in children and adolescents with
      fetal alcohol spectrum disorders.
AB  - OBJECTIVES: Caregivers describe significant sleep disturbances in the vast
      majority of children and adolescents, which is diagnosed as fetal alcohol
      spectrum disorders (FASD), but objective data on sleep disorders in this
      population are almost completely lacking. Animal models suggest that intrauterine
      alcohol exposure may disrupt sleep wake patterns, cause sleep fragmentation, and
      specifically affect the suprachiasmatic nucleus, thus disrupting melatonin
      secretion. The objective of this pioneering study was to evaluate sleep and
      melatonin abnormalities in children with FASD using objective, gold-standard
      measures. METHODS: Children and adolescents (N = 36, 6-18 years) with FASD
      participated in clinical assessments by sleep specialists, overnight
      polysomnography (PSG), and a dim light melatonin onset (DLMO) test in a pediatric
      sleep laboratory. PSG was analyzed according to standardized scoring guidelines
      and sleep architecture was compared with normative data. DLMOs were determined
      and melatonin secretion curves were evaluated qualitatively to classify melatonin
      profiles. Sleep disorders were evaluated according to international diagnostic
      criteria. RESULTS: There was a high prevalence (58%) of sleep disorders. The most
      common sleep problems were parasomnias (27.9%) and insomnia (16.8%). The sleep
      studies showed lower than normal sleep efficiency and high rates of sleep
      fragmentation. Most participants (79%) had an abnormal melatonin profile.
      CONCLUSIONS: This study led to the recognition that both sleep and melatonin
      secretion abnormalities are present in children with FASD. Therefore, to be
      effective in managing the sleep problems in children with FASD, one needs to
      consider both the sleep per se and a possible malfunction of the circadian
      regulation.

PMID- 27692278
TI  - Default mode network disturbances in restless legs syndrome/Willis-Ekbom disease.
AB  - BACKGROUND: The unusual sensations of restless legs syndrome/Willis-Ekbom disease
      (RLS/WED) are induced by rest or a low arousal state with a circadian variation
      in the threshold for induction. It has been suggested that the emergence of
      RLS/WED symptoms relates to abnormal brain functions dealing with internally
      generated stimuli. The purpose of this study was to investigate the changes in
      the default mode network (DMN) in RLS/WED subjects. METHODS: Sixteen drug-naive,
      idiopathic, RLS/WED subjects, and 16 age-matched and gender-matched healthy
      subjects were scanned in an asymptomatic resting state. A comparison of the DMN
      was conducted between the two groups. Resting state functional magnetic resonance
      imaging (MRI), Korean versions of the International RLS scale, and other sleep
      questionnaires were used. RESULTS: The results showed reductions in the DMN
      connectivity in the left posterior cingulate cortex, the right orbito-frontal
      gyrus, the left precuneus, and the right subcallosal gyrus of the RLS/WED
      subjects. The DMN connectivity was increased in sensory-motor-associated
      circuits, which included the right superior parietal lobule, the right
      supplementary motor area, and the left thalamus. In addition, the connectivity
      between the DMN and thalamus was negatively correlated with that in the orbito
      frontal gyrus and the subcallosal gyrus in the subjects. CONCLUSIONS: The results
      showed disturbances of the DMN in RLS/WED subjects that influence the thalamic
      relay sensory-motor-associated circuit. These findings may underscore the fact
      that RLS/WED subjects have disturbances in default mode network functions
      involving internal stimuli in the resting state. This may be related to
      compensatory changes to maintain resting.

PMID- 27692279
TI  - Factors predisposing to worsening of sleep apnea in response to fluid overload in
      men.
AB  - OBJECTIVES: Obstructive sleep apnea (OSA) is highly prevalent in patients with
      fluid-retaining conditions. Using bioimpedance measurements, previous studies
      have shown that the greater the amount of fluid redistributed from the legs to
      the neck overnight, the greater the severity of OSA. Our objective was to
      investigate factors that predispose the development or worsening of OSA in
      response to experimental fluid overload. METHODS: Fifteen normotensive and non
      obese adult men with and without OSA underwent polysomnography (PSG) during which
      normal saline was infused intravenously at a minimal rate to keep the vein open
      (control) or as a bolus of 22 ml/kg body weight (approximately 2 L) in a random
      order and crossed over after a week. RESULTS AND CONCLUSIONS: Before and after
      sleep, neck circumference and bioimpedance were measured to calculate neck
      resistance, reactance, phase angle, and fluid volume. Subjects who experienced
      more than a twofold increase in apnea-hypopnea index (AHI) or obstructive AHI
      from control to intervention and had an AHI>10 during intervention were
      considered susceptible to the development or worsening of OSA. Baseline neck
      circumference and phase angle before saline infusion were independently
      associated with increased susceptibility to developing or worsening OSA in
      response to saline infusion. In non-obese men, a larger neck circumference and
      bioimpedance phase angle of the neck, which may be associated with larger
      pharyngeal tissue content, is associated with increased susceptibility for
      worsening of OSA in response to fluid overloading.

PMID- 27692281
TI  - Correlates of self-reported weekday sleep duration in adolescents: the 18-year
      follow-up of the 1993 Pelotas (Brazil) Birth Cohort Study.
AB  - OBJECTIVE: To investigate factors associated with sleep duration in adolescence.
      METHODS: Data are from the 1993 Pelotas Birth Cohort Study of 5249 live births.
      Of these individuals, 4563 were located for follow-up at 18 years of age, and
      4106 agreed to be interviewed (follow-up rate 81.3%). Sleep duration was
      continuously assessed by survey as hours per weekday. Additional covariates were
      collected during the perinatal period and at the 11- and 18-year follow-ups.
      Linear regression models were used to estimate associations between sleep
      duration and its hypothesized influences. All analyses were sex-stratified.
      RESULTS: The average sleep duration among participants was 8.4 hours (standard
      deviation 1.9). Longer sleep duration at 18 years of age was associated with the
      following perinatal factors: low maternal schooling, low family income, maternal
      black skin color, and low birth weight; and with the following factors measured
      at 18 years of age: being out of school, low achieved schooling, low family
      income, absence of depressive symptoms, and high screen time. CONCLUSION: Social
      and demographic variables may play an important role in determining adolescents'
      sleep duration, but the nature of these relationships in Brazil may differ from
      those observed in higher-income contexts.

PMID- 27692280
TI  - Association of urinary melatonin levels and aging-related outcomes in older men.
AB  - BACKGROUND: Circadian disruptions can contribute to accelerated aging, and the
      circadian system regulates cognitive and physical functions; therefore, circadian
      markers (eg, melatonin) may be associated with key aspects of healthy aging and
      longevity. OBJECTIVE: To evaluate urinary melatonin levels in relation to
      cognitive function, physical function, and mortality among 2,821 older men in the
      Osteoporotic Fractures in Men Study DESIGN: Cohort study. MEASUREMENTS: In 2003
      2005, participants provided first-morning spot urine samples, which were assayed
      for 6-sulfatoxymelatonin (the primary melatonin metabolite in urine); cognitive
      and physical function assessments were completed twice, at baseline and an
      average of 6.5 years later. Participant deaths were confirmed by central review
      of death certificates over a mean of 9.2 years of follow up. RESULTS: In
      multivariable-adjusted regression models, we observed a significant trend of
      better Digit Vigilance Test scores (ie, decreased time to completion) at baseline
      across increasing melatonin quartiles (p-trend = 0.01); however, mean time-to
      completion scores did not significantly differ comparing extreme quartiles (group
      means: 547.1 seconds (95% CI: 533.6, 560.6) versus 561.3 seconds (95% CI: 547.8,
      574.9)), and there were no associations of urinary melatonin levels with other
      cognitive test scores, or any cognitive change scores over time. Furthermore,
      melatonin levels were not related to physical function scores (p-trends = 0.4 for
      walking speed, 0.7 for chair stands, and 0.6 for grip strength in fully-adjusted
      models) or mortality risk (p-trend = 0.3 in the fully-adjusted model).
      CONCLUSION: We found little evidence of associations between urinary melatonin
      levels and key measures of healthy aging and mortality in this cohort of older
      men. Further research should explore the relation of melatonin, particularly if
      assessed earlier in life, and other circadian markers with healthy aging
      outcomes.

PMID- 27692282
TI  - The effect of second-generation antipsychotic drugs on sleep parameters in
      patients with unipolar or bipolar disorder.
AB  - Sleep disturbances predominantly take the form of insomnia in patients with
      unipolar disorder, while patients with bipolar disorder show a decreased need for
      sleep. Sleep impairment in these patients is a risk factor for the development of
      a major depressive episode and suicidal behavior. Administration of second
      generation antipsychotics (SGAs) olanzapine, quetiapine, and ziprasidone as
      augmentation therapy or monotherapy to unipolar and bipolar disorder patients,
      respectively, has been shown to improve sleep continuity and sleep architecture.
      Thus, their use by these patients could ameliorate their sleep disorder.

PMID- 27692283
TI  - Food allergy: Current perspectives.

PMID- 27692284
TI  - Retraction notice to "Dopamine induces an optimism bias in rats - Pharmacological
      proof for the translational validity of the ambiguous-cue interpretation test"
      [Behav. Brain Res. 297 (2016) 84-90].

PMID- 27692285
TI  - Mesothelial cells and peritoneal homeostasis.
AB  - The mesothelium was traditionally thought to be a simple tissue with the sole
      function of providing a slippery, nonadhesive, and protective surface to allow
      easy movement of organs within their body cavities. However, our knowledge of
      mesothelial cell physiology is rapidly expanding, and the mesothelium is now
      recognized as a dynamic cellular membrane with many other important functions.
      When injured, mesothelial cells initiate a cascade of processes leading either to
      complete regeneration of the mesothelium or the development of pathologies such
      as adhesions. Normal mesothelial healing is unique in that, unlike with other
      epithelial-like surfaces, healing appears diffusely across the denuded surface,
      whereas for epithelium healing occurs solely at the wound edges. This is because
      of a free-floating population of mesothelial cells which attach to the injured
      serosa. Taking advantage of this phenomenon, intraperitoneal injections of
      mesothelial cells have been assessed for their ability to prevent adhesion
      formation. This review discusses some of the functions of mesothelial cells
      regarding maintenance of serosal integrity and outlines the mechanisms involved
      in mesothelial healing. In addition, the pathogenesis of adhesion formation is
      discussed with particular attention to the potential role of mesothelial cells in
      both preventing and inducing their development.

PMID- 27692286
TI  - Microsurgical principles and postoperative adhesions: lessons from the past.
AB  - "Microsurgery" is a set of principles developed to improve fertility surgery
      outcomes. These principles were developed progressively based on common sense and
      available evidence, under control of clinical feedback obtained with the use of
      second-look laparoscopy. Fertility outcome was the end point; significant
      improvement in fertility rates validated the concept clinically. Postoperative
      adhesion formation being a major cause of failure in fertility surgery, the
      concept of microsurgery predominantly addresses prevention of postoperative
      adhesions. In this concept, magnification with a microscope or laparoscope plays
      a minor role as technical facilitator. Not surprisingly, the principles to
      prevent adhesion formation are strikingly similar to our actual understanding:
      gentle tissue handling, avoiding desiccation, irrigation at room temperature,
      shielding abdominal contents from ambient air, meticulous hemostasis and lavage,
      avoiding foreign body contamination and infection, administration of
      dexamethasone postoperatively, and even the concept of keeping denuded areas
      separated by temporary adnexal or ovarian suspension. The actual concepts of
      peritoneal conditioning during surgery and use of dexamethasone and a barrier at
      the end of surgery thus confirm without exception the tenets of microsurgery.
      Although recent research helped to clarify the pathophysiology of adhesion
      formation, refined its prevention and the relative importance of each factor, the
      clinical end point of improvement of fertility rates remains demonstrated for
      only the microsurgical tenets as a whole. In conclusion, the principles of
      microsurgery remain fully valid as the cornerstones of reproductive microsurgery,
      whether performed by means of open access or laparoscopy.

PMID- 27692287
TI  - Disclosure in scientific meetings: should we take any steps further?

PMID- 27692288
TI  - Neglected Tropical Diseases: Research Bites Back.

PMID- 27692289
TI  - Erratum to "Family dissolution and offspring depression and depressive symptoms:
      A systematic review of moderation effects" [J. Affect. Disord. 188 (2015) 68-79].

PMID- 27692290
TI  - Retraction notice to 'Where, when, how high, and how long? The hemodynamics of
      emotional response in psychotropic-naive patients with adolescent bipolar
      disorder'.

PMID- 27692291
TI  - Retraction notice to Deficits in emotion recognition in pediatric bipolar
      disorder: The mediating effects of irritability [JAD 144/1-2 (2013) 134-140].

PMID- 27692292
TI  - Retraction notice to "Synthesis of silver nanoparticles using A. indicum leaf
      extract and their antibacterial activity" [SAA (2014) 134C 34-39].

PMID- 27692293
TI  - Retraction notice to "Synthesis, characterization and catalytic activity of
      Silver Nanoparticles Using Tribulus terrestris Leaf Extract" [SAA (2014) 88-93].

PMID- 27692294
TI  - Standardized cell sources and recommendations for good cell culture practices in
      genotoxicity testing.
AB  - Good cell culture practice and characterization of the cell lines used are of
      critical importance in in vitro genotoxicity testing. The objective of this
      initiative was to make continuously available stocks of the characterized
      isolates of the most frequently used mammalian cell lines in genotoxicity testing
      anywhere in the world ('IVGT' cell lines). This project was organized under the
      auspices of the International Life Sciences Institute (ILSI) Health and
      Environmental Sciences Institute (HESI) Project Committee on the Relevance and
      Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing. First,
      cell isolates were identified that are as close as possible to the isolate
      described in the initial publications reporting their use in genotoxicity
      testing. The depositors of these cell lines managed their characterization and
      their expansion for preparing continuously available stocks of these cells that
      are stored at the European Collection of Cell Cultures (ECACC, UK) and the
      Japanese Collection of Research Bioresources (JCRB, Japan). This publication
      describes how the four 'IVGT' cell lines, i.e. L5178Y TK+/- 3.7.2C, TK6, CHO-WBL
      and CHL/IU, were prepared for deposit at the ECACC and JCRB cell banks.
      Recommendations for handling these cell lines and monitoring their
      characteristics are also described. The growth characteristics of these cell
      lines (growth rates and cell cycles), their identity (karyotypes and genetic
      status) and ranges of background frequencies of select endpoints are also
      reported to help in the routine practice of genotoxicity testing using these cell
      lines.

PMID- 27692295
TI  - Characterization of urban aerosol: seasonal variation of mutagenicity and
      genotoxicity of PM2.5, PM1 and semi-volatile organic compounds.
AB  - Urban particulate matter (PM) is an environmental public health concern as it has
      been classified by the IARC as carcinogenic to humans (group 1) and it's well
      known that pollutants are more associated with the finest fractions of PM. In
      this study we characterize urban aerosol in Bologna, county town of Emilia
      Romagna in the north of Italy, collecting PM2.5, PM1 and semi-volatile organic
      compounds using polyurethane foam. Samples were collected in three different
      seasons (winter, summer and autumn) and were extracted with acetone. On these
      three fractions we assessed mutagenicity using Salmonella reverse mutation test
      and genotoxicity by alkaline comet assay and micronucleus assay in human lung
      cancer cell line, A549. Organic extracts were also characterized for alkanes,
      polycyclic aromatic hydrocarbons (PAHs), nitrated and oxygenated PAHs. We also
      evaluated associations between the physicochemical parameters of samples and
      their genotoxicity. The particulate samples, collected in autumn and winter,
      indicated the presence of both base pair substitution and frameshift mutagens
      using TA98 and TA100 strains of Salmonella typhimurium and the mutagenicity was
      more associated with the finest fraction. Enhanced mutagenic response was
      observed in the absence of enzyme activation. Only a third of comet and a half of
      micronucleus assays gave positive results that, unlike Salmonella's ones, are not
      season-related. These results were compared with environmental chemicals
      concentrations and we found that Salmonella's data correlated with PAHs detected
      on PM filters and with mass concentrations, whereas the DNA damage correlate only
      with PAHs extracted from polyurethane foams. The use of different assays was
      sensitive to detect and identify different classes of airborne
      mutagenic/genotoxic compounds present in aerosol, showing that monitoring air
      quality using this methodology is relevant.

PMID- 27692296
TI  - The radioprotective effect of metformin against cytotoxicity and genotoxicity
      induced by ionizing radiation in cultured human blood lymphocytes.
AB  - Metformin is a widely prescribed drug used in the treatment of patients with type
      2 diabetes. In this study, the radioprotective effect of metformin was
      investigated against cytotoxicity and genotoxicity induced by ionizing radiation
      (IR) in human peripheral blood lymphocytes. Human lymphocytes were treated with
      metformin at concentrations 10 and 50MUM for 2h and irradiated with 6MV X-rays.
      The radiation antagonistic potential of metformin was assessed by MTT [3-(4,5
      dimethyl-2-thiaozolyl)-2,5-diphenyl-2H tetrazolium bromide] assay, chromosomal
      aberration (CA) analysis, cytokinesis blocked micronucleus (CBMN) assay, and flow
      cytometry. Observations demonstrated a radiation-dose-dependent decrease in the
      percentage of cell viability after 24h. It was found that pretreatment with
      metformin (10 and 50MUM) increased the percentage of cell viability. A highly
      significant dose modifying factor (DMF) 1.35 and 1.42 was observed for 10 and
      50MUM metformin, respectively. Metformin (10 and 50MUM) pretreatment
      significantly decreased the frequency of dicentrics (DCs), acentric fragments
      (AFs), rings (RIs), micronuclei (MN), and nucleoplasmic bridges (NPBs) in
      irradiated human peripheral blood lymphocytes. Also, treatment with metformin (10
      and 50MUM) without irradiation did not increase the number of MN, NPBs, DCs, AFs,
      RIs, and did not show a cytostatic effect in the human peripheral blood
      lymphocytes. On the other hand, metformin treatment (10 and 50MUM) 2h prior to
      irradiation significantly reduced X-radiation-induced apoptotic incidence in
      human lymphocytes. The present study demonstrates metformin to be an effective
      radioprotector against DNA damage and apoptosis induced by IR in human
      lymphocytes. These data have an important application for the protection of
      lymphocytes from the genetic damage and side-effects induced by radiotherapy in
      cancer patients.

PMID- 27692297
TI  - The utility of the in vitro micronucleus test for evaluating the genotoxicity of
      natural and manmade nano-scale fibres.
AB  - A range of fibrous materials, including several types of asbestos and carbon
      fibres with nano scale diameters that had reported positive genotoxicity data
      (predominantly clastogenicity), were tested in the in vitro micronucleus test
      (OECD 487) in GLP-compliant studies in Chinese Hamster Ovary cells. Out of eight
      materials tested, only one (crocidolite, an asbestos fibre) gave a positive
      response either in the presence or absence of metabolic activation (S9) and at
      short (3h) or extended (24h) exposure times (p<=0.001). Our data suggest that the
      commonly used tests for clastogenicity in mammalian cells require extensive
      modification before fibrous materials are detected as positive, raising questions
      about the validity of these tests for detecting clastogenic and aneugenic fibrous
      materials.

PMID- 27692298
TI  - Linking genotoxicity and cytotoxicity with membrane fluidity: A comparative study
      in ovarian cancer cell lines following exposure to auranofin.
AB  - Auranofin, an organogold compound classified as an anti-rheumatic agent is under
      phase 2 clinical trials for re-purposing to treat recurrent epithelial ovarian
      cancer. We have reported earlier that Breast cancer 1, early onset (BRCA1) mutant
      ovarian cancer cells exhibit increased sensitivity to auranofin. BRCA1 is a DNA
      repair protein whose functional status is critical in the prognosis of ovarian
      cancer. Apart from DNA repair capability of cancer cells, membrane fluidity is
      also implicated in modulating resistance to chemotherapeutics. We report here
      that membrane fluidity influences the sensitivity of ovarian cancer cell lines,
      OVCAR5 and IGROV1, to auranofin. Electron spin resonance (ESR) analysis revealed
      a more fluidized membrane in IGROV1 compared to OVCAR5. Interestingly, IGROV1
      cells were more sensitive to auranofin induced cytotoxicity than OVCAR5. In
      comparison to OVCAR5, IGROV1 cells also exhibited an increased number of DNA
      double strand breaks (DSBs) upon auranofin treatment as assessed by 53BP1
      immunostaining. Furthermore, correlation analysis demonstrated a strong positive
      correlation (r=0.856) between membrane fluidity and auranofin sensitivity in
      these cell lines. Auranofin-treated IGROV1 cells also exhibited increased
      cellular oxidation and apoptosis. Anti-oxidant, N-acetyl cysteine (NAC) inhibited
      the cellular oxidation and apoptosis in auranofin-treated ovarian cancer cells
      suggesting reactive oxygen species (ROS) mediate the anti-cancer properties of
      auranofin. Overall, our study suggests that auranofin mediates its cytotoxicity
      via ROS production in ovarian cancer cells which correlates positively with
      membrane fluidity.

PMID- 27692299
TI  - Association of single nucleotide polymorphism with arsenic-induced skin lesions
      and genetic damage in exposed population of West Bengal, India.
AB  - Long term consumption of arsenic contaminated water causes a number of
      dermatological and non-dermatological health problems and cancer. In a Genome
      Wide Association Study (GWAS) on Bangladesh population, a significant association
      of asingle nucleotide polymorphism (SNP) in the C10orf32 region (rs 9527; G>A)
      with urinary metabolites and arsenic induced skin lesions was reported. This
      study aims to evaluate the association of the C10orf32 G to A polymorphism
      (rs9527), concerned with As3MT read-through transcription, with the development
      of arsenic induced skin lesions in the arsenic exposed individuals of West
      Bengal, India. A total of 157 individuals with characteristic skin lesions
      (cases) and 158 individuals without any skin lesion (controls) were recruited for
      this study. The G>A polymorphism (rs9527) having at least one minor allele 'A'
      was found to be significantly higher in cases compared to controls, implying
      increased risk toward the development of skin lesions. The risk genotype was also
      found to be significantly associated with cytogenetic damage as measured by
      chromosomal aberrations and micronuclei formation in lymphocytes. Hence, it can
      be concluded that G>A change in the C10orf32 region plays an important role in
      arsenic induced toxicity and susceptibility.

PMID- 27692300
TI  - Upper lip swelling.

PMID- 27692301
TI  - Gene therapy for sickle cell disease.

PMID- 27692302
TI  - High-risk interim PET negative patients in Hodgkin's lymphoma.

PMID- 27692303
TI  - Direct oral anti-Xa inhibitors and vaginal bleeding.

PMID- 27692304
TI  - Staunching the rising costs of haematological health care.

PMID- 27692306
TI  - Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women
      of reproductive age on direct oral anti-factor Xa inhibitor therapy: a case
      series.
AB  - BACKGROUND: Observational data and results from post-hoc analyses in clinical
      trials suggest that direct oral factor Xa inhibitors might increase menstrual
      bleeding intensity in women of reproductive age, but the extent of this effect is
      unknown. We aimed to investigate the management and outcomes of vaginal bleeding
      complications during therapy with direct oral factor Xa inhibitors in a case
      series of women of reproductive age. METHODS: To identify individuals for
      inclusion in this case series, we searched two sources of prospectively collected
      data from women of reproductive age treated with direct oral factor Xa
      inhibitors: the non-interventional Dresden NOAC Registry (NCT01588119), which is
      based in the administrative district of Dresden (Saxony, Germany), and all
      locally archived data from phase 3 trials of direct oral factor Xa inhibitors
      done at University Hospital Carl Gustav Carus Dresden. Vaginal bleeding events
      were defined as any vaginal bleeding complications as reported by the patient. We
      collected data on type and dosage of anticoagulation; suspected or confirmed
      bleeding events, hospital admissions, and mortality; and pattern and management
      of vaginal bleeding events. For all cases of bleeding identified, we reviewed all
      available source data to identify examination results suggesting potential
      underlying anatomical causes of bleeding. FINDINGS: We identified 178 women of
      reproductive age who received direct oral factor Xa inhibitor therapy, of whom 57
      had vaginal bleeding events, including 50 who received rivaroxaban, six who
      received apixaban, and one who received edoxaban. These 57 women had 72 vaginal
      bleeding events, including 59 cases of heavy menstrual bleeding and 13 bleeding
      events unrelated to the menstrual cycle. 51 (86%) of these heavy menstrual
      bleeding events (two major bleeding events, 17 clinically relevant non-major
      bleeding events, 32 minor bleeding events) were treated conservatively (eg,
      change of oral hormone therapy or reduction, temporary interruption, or
      discontinuation of direct oral factor Xa inhibitor) and the remaining eight (14%)
      events (three major bleeding events and five clinically relevant non-major
      bleeding events) required elective surgical or interventional treatment
      (hysterectomy, curettage, ovary excision, or excision of ovarian cysts). Of the
      57 women, 13 (23%) had a second bleeding event and two (4%) had a third event.
      Nine patients had underlying anatomical abnormalities; compared with patients
      without abnormalities, these patients had more intense bleeding, more had
      recurrent bleeding (five [56%] of nine patients with abnormalities vs eight [17%]
      of 48 patients without abnormalities), and more needed surgical treatment for
      bleeding (eight [89%] of nine vs zero of 48). INTERPRETATION: Vaginal bleeding,
      particularly heavy menstrual bleeding, is a common complication in women of
      reproductive age on direct oral factor Xa inhibitor therapy. Most cases can be
      treated conservatively, but patients with severe or recurrent vaginal bleeding
      complications should be assessed for underlying anatomical abnormalities, which
      might require surgical or interventional treatment. Further data are needed to
      provide guidance on prevention and treatment of vaginal bleeding complications in
      this patient population. FUNDING: None.

PMID- 27692305
TI  - The combined role of biomarkers and interim PET scan in prediction of treatment
      outcome in classical Hodgkin's lymphoma: a retrospective, European, multicentre
      cohort study.
AB  - BACKGROUND: Early-interim fluorodeoxyglucose (FDG)-PET scan after two ABVD
      (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy courses (PET
      2) represents the most effective predictor of treatment outcome in classical
      Hodgkin's lymphoma. We aimed to assess the predictive value of PET-2 combined
      with tissue biomarkers in neoplastic and microenvironmental cells for this
      disease. METHODS: We enrolled 208 patients with classical Hodgkin's lymphoma and
      treated with ABVD (training set), from Jan 1, 2002, to Dec 31, 2009, and
      validated the results in a fully matched independent cohort of 102 patients with
      classical Hodgkin's lymphoma (validation set), enrolled from Jan 1, 2008, to Dec
      31, 2012. The inclusion criteria for both the training and validation sets were:
      the availability of a representative formalin-fixed, paraffin-embedded tissue
      sample collected at diagnosis; treatment with ABVD with or without radiotherapy;
      baseline staging and interim restaging after two ABVD courses with FDG-PET; no
      treatment change based solely on interim PET result; and HIV-negative status. We
      used Cox multivariate analysis classification and regression tree (CART) to
      compare the predictive values of these markers with that of PET-2 and to assess
      the biomarkers' ability to correctly classify patients whose outcome was
      incorrectly predicted by PET-2. FINDINGS: In multivariate analysis, PET-2 was the
      only factor able to predict both progression-free survival (hazard ratio [HR]
      33.3 [95% CI 13.6-83.3]; p<0.0001) and overall survival (HR 31.3 [95% CI 3.7
      58.9]; p=0.002). In the training set, no factor had a stronger adverse predictive
      value than a positive PET-2 scan and none was able to correctly reclassify PET-2
      positive patients. In PET-2 negative patients, expression of CD68 (>=25%) and PD1
      (diffuse or rosetting pattern) in microenvironmental cells, and STAT1 negativity
      in Hodgkin Reed Sternberg cells identified a subset of PET-2 negative patients
      with a 3 year progression-free survival significantly lower than that of the
      remaining PET-2 negative population (21 [64%] of 33 [95% CI 45.2-79.0] vs 130
      [95%] of 137 [95% CI 89.4-97.7]; p<0.0001). These findings were reproduced in the
      validation set. INTERPRETATION: The CART algorithm correctly predicted the
      response to treatment in more than a half of patients who had a relapse or
      disease progression despite a negative PET-2 scan, thus increasing the negative
      predictive value of PET-2. In keeping with preliminary results from interim PET
      response adapted clinical trials of patients with advanced Hodgkin's lymphoma,
      there might be a non-negligible proportion of treatment failures in the interim
      PET negative group treated with standard ABVD. FUNDING: Italian Association for
      Cancer Research, Bologna Association against leukaemia, lymphoma and myeloma, and
      Bologna University.

PMID- 27692307
TI  - Topical Fish Oil Application Coupling with Therapeutic Ultrasound Improves Tendon
      Healing.
AB  - Fish oil has been shown to promote collagen synthesis, and hence, connective
      tissue healing. Therapeutic ultrasound is commonly used to treat soft tissue
      injuries. This study aimed to investigate the therapeutic effect of topical fish
      oil on the management of Achilles tendon rupture, comparing normal therapeutic
      ultrasound with a combination of ultrasound and fish oil. Eighty-five Sprague
      Dawley rats underwent surgical hemitenotomy of the right medial Achilles tendon.
      The rats received daily treatment of either topical placebo ointment (control
      group [CON]), topical fish oil (FO), therapeutic ultrasound (US) or ultrasound
      with fish oil as the coupling medium (FU). The treatment started on post-surgical
      day 2 over a 2-wk or 4-wk period. On days 15 and 29, the rats were sacrificed and
      their Achilles tendons were tested for structural stiffness, ultimate tensile
      strength (UTS) and energy absorption capacity. At 2 wk, only US showed higher
      normalized UTS compared with CON (p < 0.05). At 4 wk, both US and FU demonstrated
      better UTS (p < 0.05), while both FO and FU had improved in structural stiffness
      (p < 0.05). Four wk of treatment with ultrasound using fish oil as coupling
      medium showed improvement in both structural stiffness and UTS (p < 0.05).

PMID- 27692308
TI  - Body condition is negatively associated with infection with Syngamus trachea in
      the ring-necked pheasant (Phasianus colchicus).
AB  - The role that parasites play in regulating animal populations is debated, however
      recent research hints at their pervasiveness among free-living animal
      populations. Parasites exert both direct and indirect effects on host
      populations, and can act to regulate populations. The Ring-necked pheasant is an
      important game-bird species in the UK, and large numbers of birds are released
      annually. The impact of the ubiquitous tracheal nematode, Syngamus trachea on
      pheasant populations through effects on host condition was assessed on two
      pheasant estates in the south west of England. Pheasants infected with S. trachea
      demonstrated a significant reduction in host condition compared with uninfected
      controls, with as few as one pair of worms per bird. Although there was no
      difference in worm burden between sexes, analysis of regression slopes revealed
      there was a significant difference between sexes in the magnitude of the effect
      of increasing worm burden on host condition, with detectable effects observed in
      hosts with one and three pairs of worms for males and females respectively. The
      observed reductions in host condition in birds with even sub-clinical infections
      could be the cause of poor reproductive success and survival of pheasants post
      release.

PMID- 27692309
TI  - Repeatability of strongyle egg counts in naturally infected horses.
AB  - The selective treatment of horses is used to decrease the number of anthelmintic
      treatments by only treating a proportion of animals in the population. One way to
      select animals for treatment is to identify low and high egg-shedders using
      faecal egg counts (FEC); then to treat only the high egg-shedders. The value of
      this method is enhanced if differences among individuals in the level of egg
      shedding remain consistent over time. One way to assess the stability of the
      rankings of animals over time is to measure the repeatability which is defined as
      the variance between horses divided by the total variance. The repeatability
      varies between 0 (no consistency in the values) to 1 (perfect consistency). To
      determine the repeatability of egg-shedding in naturally infected horses over
      time, 2637 FEC and raw egg counts (REC; i.e. originally counted eggs without
      multiplication factor) from 303 horses were analysed. The distribution of FEC was
      more overdispersed than a Poisson distribution. Therefore, a negative-binomial
      model was used. The within-horse-repeatability of RECs was 0.52. In a second
      analysis, we excluded horses that were treated with anthelmintic drugs during the
      study by eliminating all REC within the egg-reappearance-period. Here, the within
      horse-repeatability was very similar at 0.53. The results show that egg-shedding
      of individual horses stays fairly consistent over time. They also show that
      animals which shed relatively high numbers of nematode eggs can be identified and
      targeted for treatment.

PMID- 27692310
TI  - A model for the development and growth of the parasitic stages of Parascaris spp.
      in the horse.
AB  - Literature documenting the growth and development of Parascaris spp. infections
      was used to develop a model describing worm dynamics in the young horse. The
      model incorporates four main variables; the rate at which larvae migrate through
      host tissues to return to the small intestine, the proportion of migrating larvae
      which succeed in returning to the small intestine, the rate of growth in size of
      maturing and adult worms and the survival rate of maturing and adult worms. In
      addition, the number of eggs laid each day by adult female worms is calculated as
      a function of worm size (length) and is used to calculate faecal egg output of
      the foal. Published data describing the rate of migration through host tissues,
      and the growth of worms following their return to the small intestine, was used
      to derive relationships describing these processes. However, only limited data
      exists relating the survival of migrating larvae and mature worms in the
      intestine to host age and experience of infection. Therefore, relationships and
      coefficients describing these variables were modified so that output aligned with
      published experimental results. As a consequence, the model has not yet been
      evaluated against an independent data set, and so remains as the best 'current
      hypothesis' for the dynamics of this parasite. Hopefully, future experiments
      designed to test specific assumptions and outputs of the model will lead to a
      better understanding of the biology of this important parasite. For example, the
      most influential variable in determining model output is the survival rate of
      worms in the small intestine. In the model, worm survival declines in response to
      both the increasing age of the horse and the increasing cumulative length of
      worms in the intestine (used as a proxy for crowding). Given the importance of
      this variable to model behaviour and the paucity of experimental data on this
      topic this would seem a priority for future study. Initial experiments using the
      model suggest that a single anthelmintic treatment, administered soon after
      patency of initial infection, may effectively control environmental contamination
      with Parascaris spp. eggs while allowing a small 'refugia' of susceptibility to
      delay the emergence of anthelmintic resistance. Further evaluations of the
      practicality of this approach may be worthwhile.

PMID- 27692311
TI  - Genetic characterization of Cryptosporidium in animal and human isolates from
      Jordan.
AB  - Little is known about the epidemiology of Cryptosporidium in Jordan and to date,
      only one genotyping study has been conducted on Cryptosporidium isolates from
      Jordanian children. In the present study, a total of 284 faecal samples from
      Jordanian cattle, sheep, goats and chicken and 48 human faecal samples were
      screened for the presence of Cryptosporidium using an 18S quantitative PCR (qPCR)
      and a C. parvum/C. hominis specific qPCR at a lectin locus. Of these, 37 of 284
      animal faecal samples were positive by qPCR at the 18S locus giving an overall
      prevalence of 11.6%. The point prevalence of Cryptosporidium in chickens, sheep,
      horses, cattle and goats ranged from 4.8% (chickens) to 18.7% (cattle). A total
      of six species were detected; C. xiaoi (n=9),C. andersoni (n=7),C. ryanae
      (n=5),C. parvum (n=4),C. baileyi (n=1) and a genetically distinct and potentially
      novel species in two isolates from horses. Sub-genotype analysis of the 4 C.
      parvum isolates at the 60-kDa glycoprotein (gp60) locus identified subtype
      IIaA19G2R1 (n=2) and IIaA16GR1 (n=2). For the human samples, 4 positives (8.3%
      prevalence) were detected. Of these, two were C. parvum (subtypes IIdA20G1 and
      IIaA15G2R1) and two were C. hominis (subtypes 1bA9G3 and 1bA10G2R2). Further
      studies are required to better understand the epidemiology and transmission of
      Cryptosporidium in Jordan.

PMID- 27692312
TI  - Synergistic action of fatty acids, sulphides and stilbene against acaricide
      resistant Rhipicephalus microplus ticks.
AB  - Six compounds in a methanolic extract of Petiveria alliacea stem (cis-stilbene;
      benzyl disulphide; benzyl trisulphide; and methyl esters of hexadecanoic acid,
      octadecadienoic acid and octadecenoic acid) are known to exercise acaricide
      activity against cattle tick Rhipicephalus microplus larvae and adults. The
      synergistic effect of 57 combinations of these six compounds on acaricide
      activity against R. microplus was evaluated. Larvae immersion tests produced the
      lethal concentrations needed to kill 50% (LC50) and 99% (LC99) of the population.
      Adult immersion tests produced rates (%) for mortality, oviposition inhibition
      and eclosion inhibition. Individually, none of the compounds (1% concentration)
      exhibited acaricide activity (mortality <=2.3%). When combined, however, nine
      mixtures exhibited a synergistic increase in activity, with high mortality rates
      (>=92%) in larvae. Values for LC50 ranged from 0.07 to 0.51% and those for LC99
      from 0.66 to 5.16%. Thirty six compound mixtures had no significant activity
      (mortality <=30%) against larvae. Two mixtures exhibited synergism against
      adults, with high rates (>=92%) of oviposition inhibition. The mixtures based on
      the benzyl disulphide+benzyl trisulphide pairing produced a synergistic effect
      against acaricide-resistant R. microplus larva and adults, and are therefore the
      most promising combination for controlling this ubiquitous ectoparasite.

PMID- 27692313
TI  - Toxoplasma gondii detection in cattle: A slaughterhouse survey.
AB  - Toxoplasmosis is a zoonotic disease caused by the protozoan parasite Toxoplasma
      gondii. Ingestion of raw or undercooked meat containing viable cysts has been
      suggested to be a major source of T. gondii infection in humans. Suboptimal
      performance of serological assays in cattle has traditionally precluded accurate
      quantification of the extent to which cattle populations are infected and their
      meat harbour tissue cysts. In the absence of accurate estimates of the level of
      infection in the animal population, assessments of likely human exposure through
      the consumption of cattle meat remain highly speculative. Following the
      development of novel and sensitive molecular methods that can be applied to the
      relatively large numbers of samples required in observational studies, the first
      quantitative estimates of the frequency of T. gondii in meat samples from
      naturally infected cattle have become available recently. Such estimates are
      critical for the development of quantitative risk assessment models that could be
      used to inform food safety policies. The aim of this study was to generate the
      first estimates of the prevalence of T. gondii infection in a sample of cattle
      exposed to natural levels of infection and slaughtered for human consumption in
      the UK under commercial conditions. Such estimates provide great value to the
      global assessment of T. gondii burden given the scarcity of data available on the
      frequency of natural infection in cattle populations worldwide. Between October
      2015 and January 2016 diaphragm samples were collected from 305 animals,
      slaughtered in ten commercial slaughterhouses across the UK. Movement histories
      showed that the animals sampled (41.6% females and 58.4% males) had passed
      through a total of 614 farms and 40 livestock markets across the country. Five
      animals (1.6%) were deemed positive for T. gondii following magnetic capture real
      time PCR, confirmed by amplicon sequencing. The true prevalence of infection was
      estimated to be 1.79%. All positive animals were male, none of whom had been on
      the same farm and/or livestock market before slaughter and there was no apparent
      geographic pattern. The results from this study suggest a low level of infection
      in cattle raised and slaughtered in the UK and can be used to populate the first
      stages of formal risk assessments to quantify the likely extent of human exposure
      to T. gondii through the consumption of beef with relevance to the UK, EU and
      rest of the world.

PMID- 27692314
TI  - Comparison of genotypes of Toxoplasma gondii in domestic cats from Australia with
      latent infection or clinical toxoplasmosis.
AB  - Whether Toxoplasma gondii genotype is associated with disease severity in
      naturally occurring toxoplasmosis in domestic cats is unknown. The aim of this
      study was to compare genotypes of T. gondii in latently infected cats with those
      in cats with clinical toxoplasmosis. Results of a PCR targeting the B1 gene to
      detect T. gondii DNA were positive in tissue samples from 11 of 17 (65%)
      seropositive cats tested including four with clinical toxoplasmosis and seven
      with latent infections, as determined by serology, histologic findings and
      immunohistochemistry. Three of the four cats with clinical toxoplasmosis were
      immunosuppressed. Complete genotyping was performed in seven cats using PCR-RFLP
      at 12 loci (SAG1, 5'SAG2 and 3'SAG2, altSAG2, SAG3, BTUB, GRA6, c22-8, c29-2,
      L358, PK1 and Apico) and direct sequencing of the multi-copy B1 gene. Partial
      genotyping using six loci was performed in one cat with latent infection. T.
      gondii type II (ToxoDB genotype #3) was determined in four cats with clinical
      toxoplasmosis and three cats with latent toxoplasmosis Novel T. gondii B1 gene
      polymorphisms were detected in two strains (at nucleotide posititions 233, 366
      and 595) and a B1 gene polymorphism unique to Australia was identified in another
      (guanine/adenine at nucleotide position 378). One cat was co-infected with two or
      more type-II like strains at 3'SAG2. The results of this study suggest that the
      infecting T. gondii genotype, based on these 12 loci, is not a determinant of
      clinical disease in cats naturally infected with T. gondii and type II strains
      are prevalent in Australia.

PMID- 27692315
TI  - Protection of ewes against Teladorsagia circumcincta infection in the
      periparturient period by vaccination with recombinant antigens.
AB  - Teladorsagiosis is a major production-limiting disease in ruminants in temperate
      regions throughout the world and one of the key interventions in the management
      of the disease is the prevention of pasture contamination with Teladorsagia
      circumcincta eggs by ewes during the periparturient relaxation in immunity which
      occurs in the period around lambing. Here, we describe the immunisation of twin
      bearing ewes with a T. circumcincta recombinant subunit vaccine and the impact
      that vaccination has on their immune responses and shedding of parasite eggs
      during a continuous T. circumcincta challenge period spanning late gestation and
      lactation. In ewes which displayed a clear periparturient relaxation in immunity,
      vaccination resulted in a 45% reduction in mean cumulative faecal egg count
      (cFEC, p=0.027) compared to control (immunised with adjuvant only) ewes.
      Recombinant antigen-specific IgG and IgA, which bound each of the vaccine
      antigens, were detected in the serum of vaccinated ewes following each
      immunisation and in colostrum taken from vaccinated ewes post-partum whereas low
      levels of antigen-specific IgG were detected in serum and colostrum from control
      ewes. Antigen-specific IgG and IgA levels in blood collected within 48h of birth
      from lambs largely reflected those in the colostrum of their ewes.

PMID- 27692316
TI  - Acaricidal activity of methanol extract of Acmella oleracea L. (Asteraceae) and
      spilanthol on Rhipicephalus microplus (Acari: Ixodidae) and Dermacentor nitens
      (Acari: Ixodidae).
AB  - We evaluated the acaricidal activity of Acmella oleracea methanol extract and
      spilanthol on Rhipicephalus microplus and Dermacentor nitens. The extract was
      made through maceration with methanol. From this extract, a dichloromethane
      fraction with 99% spilanthol was obtained and tested on R. microplus larvae and
      engorged females and D. nitens larvae. For evaluation against larvae, the
      modified larval packet test was used, and both the methanol extract and
      dichloromethane fraction were tested at concentrations of 0.2-50mg/mL. The
      modified larval packet test was also used in the lethal time (LT) test, with the
      methanol extract at a concentration of 12.5mg/mL and the percentage mortality was
      assessed after 15, 30, 45, 60, 75, 90, 120min and 24h. The 50% lethal time
      calculation (LT50) was performed in this test. The engorged female test was
      performed with R. microplus only, at concentrations of 25-200mg/mL for methanol
      extract and 2.5-20.0mg/mL for spilanthol. The methanol extract caused 100%
      mortality of the R. microplus and D. nitens larvae at concentrations of 3.1 and
      12.5mg/mL, respectively. Spilanthol resulted in 100% mortality of R. microplus
      larvae at concentration of 1.6mg/mL and of D. nitens at 12.5mg/mL. In the lethal
      time assay using the methanol extract, the mortality rate was 100% for R.
      microplus and D. nitens larvae after 120min and 24h, with LT50 values of 38 and
      57min, respectively. In the test of females, the egg mass weight and the hatching
      percentage of the groups treated with concentrations equal to or higher than
      50.0mg/mL of methanol extract were significantly reduced (p<0.05), while for
      spilanthol, the reduction of the egg mass weight and hatching percentage occurred
      from concentrations of 10.0mg/mL and 2.5mg/mL, respectively. Females treated with
      200.0mg/mL of extract died before starting oviposition, resulting in 100%
      effectiveness, while the best efficacy for spilanthol was 92.9% at a
      concentration of 20.0mg/mL. Thus we conclude that the methanol extract of A.
      oleracea and spilanthol have acaricidal activity against R. microplus and D.
      nitens.

PMID- 27692317
TI  - Lungworm Heterostrongylus heterostrongylus Travassos, 1925 from the black-eared
      opossum in South America: Morphologic, histopathological and phylogenetic
      aspects.
AB  - Nematode parasites of the cardiopulmonary system of livestock and pet animals
      have been receiving attention due to the pathogenic effects they produce in the
      course of the infection. However, parasitism in wild animals by metastrongilid
      nematodes has been neglected, resulting in potential risk to wildlife.
      Heterostrongylus heterostrongylus is the etiological agent of bronchial pneumonia
      in the black-eared opossum, Didelphis aurita, a widely distributed marsupial
      frequently reported to inhabit areas from wild environments to peri-urban spaces.
      In this study, we reassessed the taxonomy of H. heterostrongylus, describing and
      comparing morphology of L1 and L3 larvae and adult worms with closely related
      angiostrongilids, and inferring phylogenetic affinities within the family
      Angiostrongylidae; we also detailed histopathological reactions under natural
      infection. Ultrastructural morphology and light microscopy confirmed cephalic
      structures with well-developed trilobed lips, patterns of caudal bursa rays,
      spicules shape, terminal anal aperture and presence of the ventral protuberance
      in L3 larvae, characteristics present for the family Angiostrongylidae. Our
      molecular phylogenetic analyses, based on the partial small subunit (SSU) 18S
      rRNA gene, suggested that H. heterostrongylus and Didelphostrongylus hayesi are
      closely related. Pathological analyses agreed with previous findings, showing
      that cardiopulmonary parasitism provokes verminous pneumonia and mucous
      bronchiolitis with hypertrophy of the smooth bronchiolar muscle. These data
      confirmed that H. heterostrongylus represents a pulmonary pathogen in D. aurita,
      produces severe pathological effects, and may represent risk to domestic and wild
      animals.

PMID- 27692318
TI  - First report of the in vitro nematicidal effects of camel milk.
AB  - Antipathogenic properties of camel milk have been investigated to substitute for
      drugs hence overcome drug resistance. The main objective of this present study
      was to investigate the anthelmintic activity of camel milk in relationship to its
      chemical composition. In vitro anthelmintic effects of camel milk against
      Haemonchus contortus from sheep were ascertained by egg hatching and worm
      motility inhibitions in comparison to milks from cow, ewe and goat as well as a
      reference drug albendazole. Chemical composition revealed that camel milk has
      higher contents of protective protein (lactoferrin) and vitamin C than other
      species' milk. It showed ovicidal activity at all tested concentrations and
      completely inhibited egg hatching at a concentration close to 100mg/mL
      (inhibitory concentration (IC50)=42.39mg/mL). Camel milk revealed in vitro
      activity against adult parasites in terms of the paralysis and/or death of the
      worms at different hours post treatment. After 8h of exposure, it induced 100%
      mortality at the highest tested concentration. There was 82.3% immobility of
      worms in albendazole 8h post-exposition. No such effects were seen with the other
      species' milks. Bioactive compounds such as lactoferrin and vitamin C may be
      involved in such an effect. To our knowledge, these results depict for the first
      time that camel milk possesses in vitro anthelmintic properties and further in
      vitro and in vivo trials against different parasite species and stages are
      required to make use of this milk for the control of gastrointestinal nematode
      parasites.

PMID- 27692319
TI  - Anti-helminthic activity of Momordica charantia L. against Fasciola hepatica eggs
      after twelve days of incubation in vitro.
AB  - Fasciolosis, a parasitic disease caused by the trematode Fasciola hepatica
      underreported is expanding both in human and animal population, throughout the
      world. The constant use of synthetic drugs to treat this condition has led to the
      natural selection of resistant strains of the parasite. Hence, there is a growing
      focus on the potential anti-helminthic properties of medicinal plants and
      phytopharmaceuticals. The current study assessed the potential anti-fasciolicide
      action of Momordica charantia leaf extracts and fractions on the eggs of F.
      hepatica parasites. The lyophilized crude extract (CE) of M. charantia leaves and
      its sub-fractions, obtained from liquid-liquid partitioning with organic
      solvents, were analysed by High Performance Liquid Chromatography (HPLC),
      suspended in 1% DMSO and used in in vitro tests. Quadruplicates of 50F. hepatica
      eggs were incubated at 23 degrees C with M. charantia leaf CE in different
      concentrations. After 12days no larvae were formed in eggs incubated with CE
      concentrations above 12.5mg/mL. Eggs incubated with CE sub-fractions at
      concentrations of 1000, 100, 10, 1, 0.1, 0.01MUg/mL affected embryonic
      development, with n-butanol presenting the strongest inhibition of miracidia
      formation. In contrast, on the 12th day, 90% of the miracidia hatched in the
      control experiments using 0.03% DMSO whereas embryogenesis was completely
      abolished with any concentration of albendazole sulphoxide ABZ(SO). Chemical
      analysis of the CE and sub-fractions revealed a prominent presence of flavonoids.
      HPLC-MS confirmed Quercetin to be one of the main flavonoids present in the CE
      and the n-butanol subfraction. This is the first study to analyse the potential
      anti-fasciolicide action of M. charantia leaf CE and subfractions.

PMID- 27692320
TI  - Evaluation of pharmacokinetics and efficacy of ivermectin following oral
      administration in dogs against experimental infection of Ctenocephalides felis
      felis and Rhipicephalus sanguineus.
AB  - With the increasing number of pets in home the human-animal relationship is
      increasingly close and care about control disease growing. Ivermectin (IVM) is
      frequently used because its proven safety. IVM is recommended for the treatment
      of demodectic scabies and prevention of heartworm in dogs, but informally is
      extremely used to control of Ctenocephalides felis felis and Rhipicephalus
      sanguineus. The aim of this study is evaluate the use of IVM in dogs, by the oral
      route at 0.6MUg/kg dose, against experimental infection of these parasites using
      the construction of the plasma concentration curve and efficacy study. A IVM
      quantification method in canine plasma using HPLC-FL was developed and validated
      based on RE n degrees 899/03 ANVISA. The samples collected during the efficacy
      test was analyzed by this validated method and prove Cmax of 350ng/mL at 4h
      (tmax) and AUC of 8411ng/h/mL. Spite of formulation have shown good absorption,
      the highest efficiency values found for Rhipcephalus sanguineus and
      Ctenocephalides felis felis were very low, 35% and 67% respectively,
      demonstrating this not be the most appropriate treatment for the control of these
      parasites.

PMID- 27692321
TI  - Ectoparasites of free-roaming domestic cats in the central United States.
AB  - Free-roaming domestic cat (Felis catus) populations serve as a valuable resource
      for studying ectoparasite prevalence. While they share a similar environment as
      owned cats, free-roaming cats do not receive routine veterinary care or
      ectoparasiticide application, giving insight into parasite risks for owned
      animals. We examined up to 673 infested cats presented to a trap-neuter-return
      (TNR) clinic in the central United States. Ectoparasite prevalences on cats were
      as follows: fleas (71.6%), ticks (18.7%), Felicola subrostratus (1.0%),
      Cheyletiella blakei (0.9%), and Otodectes cynotis (19.3%). Fleas, ticks, and O.
      cynotis were found in all months sampled. A total of 1117 fleas were recovered
      from 322 infested cats. The predominate flea recovered from cats was
      Ctenocephalides felis (97.2%) followed by Pulex spp. (2.8%), Cediopsylla simplex
      (0.6%), and Nosopsyllus fasciatus (0.6%). A total of 373 ticks were recovered
      from 126 infested cats. The predominate tick species was Amblyomma americanum
      (65.9%) followed by Ixodes scapularis (32.5%), Dermacentor variabilis (10.3%),
      and Rhipicephalus sanguineus (0.8%). Immature tick stages accounted for 54.7% of
      all ticks found, highlighting an under-appreciated source of tick burden on
      domestic cats. The results of this study emphasize the importance of year-round
      use of ectoparasiticides with both insecticidal and acaricidal activity on
      domestic cats.

PMID- 27692322
TI  - TLR-2 and TLR-4 transcriptions in unstimulated blood from dogs with leishmaniosis
      due to Leishmania infantum at the time of diagnosis and during follow-up
      treatment.
AB  - Innate immunity, in particular, the role of toll-like receptors (TLRs), has not
      been extensively studied in canine L. infantum infection. The main aim of this
      study was to determine the transcription of TLR2 and TLR4 in the blood of dogs
      with natural clinical leishmaniosis at the time of diagnosis and during treatment
      follow-up and subsequently correlate these findings with clinical, serological
      and parasitological data. Forty-six Leishmania-seropositive sick dogs with a high
      antibody level at the time of diagnosis were studied and compared with 34 healthy
      seronegative dogs. Twenty-two of these sick dogs were treated with meglumine
      antimoniate and allopurinol and followed-up at 30, 180 and 365days following the
      start of treatment. Clinical status was defined by a thorough physical
      examination, complete blood count, biochemistry profile, electrophoresis of serum
      proteins, and urinary protein/creatinine ratio (UPC). EDTA blood was stored in
      RNAlater(r) solution before RNA extraction and cDNA production were performed.
      TLR2, TLR4 and three reference genes (HPRT-1, CG14980 and SDHA) were studied in
      each blood sample by real time PCR. The relative quantification of TLR2 was
      higher (mean 3.5) in sick dogs when compared with seronegative healthy dogs (mean
      1.3; P=0.0001) while the relative quantification of TLR4 was similar in both
      groups. In addition, the relative quantification of TLR2 significantly decreased
      during follow-up at all time points compared with day 0 whereas no changes were
      observed with TLR4 transcription. A significant positive correlation was noted
      between TLR2 and UPC, total protein, beta and gamma globulins, specific L.
      infantum antibodies and blood parasite load while a negative correlation was
      observed with albumin, albumin/globulin ratio, hematocrit and hemoglobin. TLR4
      transcript did not correlate with any parameter. These findings indicate an up
      regulation of TLR2 transcription in unstimulated blood in naturally infected sick
      dogs as compared to healthy dogs suggesting active innate immune and
      proinflammatory responses. In addition, TLR2 transcription is reduced with
      clinical improvement during treatment. In contrast, TLR4 transcription appears to
      be similar among groups at the time of diagnosis with no changes during treatment
      follow-up suggesting a less important role for this TLR in clinical canine
      leishmaniosis.

PMID- 27692323
TI  - The association between seizures and deposition of collagen in the brain in
      porcine Taenia solium neurocysticercosis.
AB  - Neurocysticercosis caused by infection with Taenia solium is a significant cause
      of epilepsy and seizures in humans. The aim of this study was to assess the
      association between seizures and the deposition of collagen in brain tissue in
      pigs with T. solium neurocysticercosis. In total 78 brain tissue sections from
      seven pigs were examined histopathologically i.e. two pigs with epileptic
      seizures and T. solium cysts, four pigs without seizures but with cysts, and one
      non-infected control pig. Pigs with epileptic seizures had a larger amount of
      collagen in their brain tissue, showing as large fibrotic scars and moderate
      amount of collagen deposited around cysts, compared to pigs without seizures and
      the negative control pig. Our results indicate that collagen is likely to play a
      considerable part in the pathogenesis of seizures in T. solium
      neurocysticercosis.

PMID- 27692324
TI  - Genetic characterization of Neospora caninum from aborted bovine foetuses in
      Aguascalientes, Mexico.
AB  - The cyst-forming protozoan parasite Neospora caninum is one of the main causes of
      bovine abortion worldwide and is of great economic importance in the cattle
      industry. Recent studies have revealed extensive genetic variation among N.
      caninum isolates based on multilocus microsatellite genotyping. Currently, the
      most extensive study reported is based on the N. caninum genotyping of 96 samples
      from four countries on two continents (Spain, Argentina, Germany and Scotland)
      that demonstrate different clusters of multilocus genotypes (MLGs) implicated in
      cattle abortions as well as the population sub-structuring of N. caninum, which
      is partially associated with the geographical origin. The aim of this study was
      to genotype N. caninum from aborted bovine foetuses that originated from Mexico
      within the region of Aguascalientes and to investigate their genetic diversity.
      Parasite DNA was detected in 27 out of the 63 analysed foetuses recovered from 10
      different herds. Complete or nearly complete profiles based on 9 microsatellite
      markers were obtained from 11 samples. Diverse N. caninum MLGs were implicated in
      the occurrence of abortion in each herd. All of the Mexican MLGs differed from
      the MLGs previously determined for the Argentinean, Spanish, German and Scottish
      N. caninum populations. The Mexican MLGs failed to cluster by eBURST analyses.
      The MLG relationships using PCoA showed a close genetic relationship between the
      Spanish population and a portion of the Mexican population, but a more distant
      genetic relationship with the Argentinean genotypes. These results demonstrate
      the genetic diversity of N. caninum in the studied areas that differed from other
      populations of N. caninum around the world.

PMID- 27692325
TI  - Angiostrongylus chabaudi in felids: New findings and a review of the literature.
AB  - Cardiopulmonary infections by Angiostrongylus chabaudi affect domestic and wild
      felids but, due to limited information on the biology of this nematode, its
      pathogenicity remains unclear. This article describes the histopathological
      alterations associated with Angiostrongylus infection in a wildcat from Bulgaria,
      and reviews current literature on this feline angiostrongylid. Nematodes were
      isolated from lung lavage and faecal samples of a road killed wildcat in Southern
      Bulgaria. The morphological identification of parasite larvae as A. chabaudi was
      confirmed by molecular analysis of part of the 18S ribosomal RNA gene. Upon
      histopathological examination, severe granulomatous pneumonia, ranging from
      multifocal to coalescing, and pulmonary vascular lesions were observed. Extensive
      alveolar collapse, alveolar emphysematous changes, parenchymal haemorrhages and
      small artery wall hyperplasia were observed in the parenchyma adjacent to the
      granulomas. Histopathological examination revealed the presence of cross-sections
      of adult female parasites within the lumen of the pulmonary artery branches, the
      intima altered markedly by subendothelial proliferation and oedematous changes.
      This study compliments current knowledge of the pathogenesis of feline
      angiostrongylosis by A. chabaudi in wildcats, as well as of the distribution of
      this little-known parasite.

PMID- 27692327
TI  - Papaya latex supernatant has a potent effect on the free-living stages of equid
      cyathostomins in vitro.
AB  - The control of equid gastrointestinal nematodes in developed countries, in
      particular the cyathostomins, is threatened by high levels of anthelmintic
      resistance. In recent years, there has been increasing interest in the evaluation
      of traditional 'ethnoveterinary' medicines as alternatives to chemical
      anthelmintics. The cysteine proteinases (CPs), a group of enzymes derived from
      fruits such as papaya (Carica papaya), pineapple (Ananas comosus) and figs (Ficus
      spp.), have shown good efficacy against adult stages of a range of parasitic
      nematodes, in vitro and in vivo. The efficacy of CPs against cyathostomins
      remains to be explored. In this study, the efficacy of a crude preparation of
      CPs, papaya latex supernatant (PLS), against the free-living stages of
      cyathostomins was evaluated using two in vitro tests, the egg hatch test (EHT)
      and the larval migration inhibition test (LMIT). It was demonstrated that PLS had
      a potent effect in the EHT, with EC-50 values in the range of 0.12-0.22MUM. At
      concentrations above 6.25MUM the eggs did not develop, below this concentration
      the L1 developed but they lost integrity of the cuticle upon hatching. These
      effects were inhibited by pre-incubation of PLS with the CP inhibitor L-trans
      epoxysuccinyl-l-leucylamido-(4-guanidino butane) (E64), indicating that CPs were
      responsible for the anti-parasitic activity. A dose-dependent inhibition of
      migration of third stage larvae (L3) in the LMIT was demonstrated at higher
      concentrations of PLS, with EC-50 values in the range of 67.35-106.31MUM.
      Incubation of PLS with E64 prior to use in the LMIT did not reverse the anti
      migratory effect, suggesting that CPs were not responsible for the reduced
      migration of cyathostomin L3 and that PLS also contains an additional active
      compound. This is the first report of PLS and/or CPs showing activity against the
      free-living stages of a parasitic helminth. In addition, it suggests that
      cyathostomins are highly sensitive to the effects of CPs and further evaluation
      of their efficacy against parasitic stages and in vivo are strongly indicated.

PMID- 27692326
TI  - Resistance of Haemonchus sp. to monepantel and reduced efficacy of a derquantel /
      abamectin combination confirmed in sheep in NSW, Australia.
AB  - Early in 2015, sheep in a summer rainfall area of NSW, Australia, displayed signs
      of haemonchosis despite treatment with monepantel. A faecal egg count reduction
      test (FECRT) was performed on yearlings with natural field infections using
      various anthelmintics. Only a four-way combination drench achieved a reduction in
      faecal egg count (FEC) greater than 95%. The combination contained abamectin,
      albendazole, levamisole and closantel. Treatments with a derquantel/abamectin
      combination, monepantel and moxidectin reduced FECs by 93, 31, and 30%
      respectively. Sheep treated with abamectin displayed an increase in FEC of 22%.
      Larval differentiation counts conducted 10days post-treatment showed that 100% of
      survivors were Haemonchus sp. This result confirms for the first time monepantel
      resistant Haemonchus in sheep in NSW, and is amongst the first of the Australian
      cases in sheep not associated with goats. A second FECRT was performed using
      sheep from the moxidectin and abamectin treatment groups in the first FECRT. In
      this second FECRT, monepantel treatment reduced FECs by 51% and 29% in the sheep
      previously treated with moxidectin and abamectin respectively. This suggests
      monepantel, in combination with moxidectin, may give some control against
      severely abamectin resistant Haemonchus.

PMID- 27692328
TI  - Efficacy of closantel against ivermectin- and fenbendazole-resistant Haemonchus
      sp. in sheep in Ontario, Canada.
AB  - In Ontario, Canada, widespread resistance to ivermectin and fenbendazole, the
      only readily available ovine anthelmintics, has been documented, primarily in
      Haemonchus sp. In other parts of the world, closantel has been used to control
      such infections; however, the drug was not currently licensed for use in Canada
      and the USA. A randomized controlled trial was conducted on six client-owned
      farms in Ontario in 2013 and 2014 to determine the efficacy of closantel
      (Flukiver(r) 5% Oral Suspension, Elanco Animal Health, 10mg/kg bodyweight)
      against ivermectin- and fenbendazole-resistant Haemonchus sp. infections in
      periparturient ewes and grazing lambs. Three farms were randomly assigned to
      treat all ewes, and three farms were randomly assigned to selectively treat
      individual ewes at lambing, using predetermined criteria. Fecal samples were
      collected from a minimum of 15 randomly selected ewes and 13 lambs per group on
      each farm at the time of treatment and approximately 14days later.
      Trichostrongyle-type fecal egg counts (FEC) were performed using a modified
      McMaster technique with a lower detection limit of 8.3 eggs per gram of feces
      (epg). Haemonchus-specific FECs were determined by multiplying FECs by the
      proportion of Haemonchus sp. identified from coproculture for each farm;
      Haemonchus-specific FEC reductions were calculated for each farm. Twenty grazing
      lambs had FECs conducted monthly, and when mean monthly FECs surpassed 200 epg,
      all lambs were randomly allocated to either closantel, positive control
      (ivermectin, fenbendazole, or levamisole) or negative control groups. Pre
      treatment Haemonchus-specific mean FECs ranged from 27 to 3359 epg in ewes and 0
      5698 epg in lambs. Efficacy of closantel against Haemonchus sp. ranged from 99%
      (95% CI: 97%-99%) to 100% in recently lambed ewes on all farms in both years
      (total n=274 ewes), and from 99% (95% CI: 98%-99%) to 100% in grazing lambs in
      both years on all but one farm (total n=171 lambs). On the latter farm, a whole
      flock treated farm, closantel efficacy in grazing lambs was 84% (95%CI: 81%-88%)
      in the first year, but 100% in the second year. Levamisole was effective against
      overall GIN in lambs on only two farms. Ivermectin and fenbendazole resistance
      continued to be present, particularly in Haemonchus sp. Closantel had excellent
      efficacy against Haemonchus sp. over the two year study period, regardless of
      treatment group, and therefore should be considered one viable component of
      sustainable integrated parasite control programs for farms with documented
      anthelmintic resistance and problems with haemonchosis.

PMID- 27692329
TI  - Greater intensity and frequency of Cryptosporidium and Giardia oocyst shedding
      beyond the neonatal period is associated with reductions in growth, carcase
      weight and dressing efficiency in sheep.
AB  - Associations between intensity and frequency of Cryptosporidium and Giardia
      shedding with growth, carcase weight and dressing% were investigated using a
      longitudinal study of 1182 lambs on eight Australian farms. Live weight was
      recorded and faecal samples were collected on three sampling occasions; weaning
      (approximately 12 weeks of age), post-weaning (approximately 19 weeks) and pre
      slaughter (approximately 29 weeks). Hot standard carcase weight (HSCW) and
      dressing% were measured at slaughter. Faecal samples were screened for presence
      and concentration of Cryptosporidium, Giardia and Haemonchus oocysts using a
      quantitative PCR. Trichostrongylid eggs were quantified with modified McMaster
      faecal worm egg count (WEC). Protozoan shedding intensity was categorised as high
      (above median oocyst concentration in positive sheep), low (below median oocyst
      concentration in positive sheep) or not detected. Shedding was also categorised
      for shedding type (no shedding, single Giardia infection, single Cryptosporidium
      infection, concurrent Giardia and Cryptosporidium infection) and lambs were
      categorised for frequency of shedding (shedding identified on 0, 1, 2 or 3
      occasions). Associations of parasite shedding intensity category, shedding type,
      shedding frequency, WEC and Haemonchus status (positive or negative) with lamb
      production were assessed using general linear models (HSCW and dressing%) and
      linear mixed effects models (live weight). High Cryptosporidium parvum shedding
      was associated with lower live weight, ranging 2.31-4.52kg over the 3 sampling
      occasions. Cryptosporidium parvum shedding was associated with less HSCW in high
      (3.22kg less) and low (3.22kg less) shedding lambs post-weaning, and high (2.21kg
      less) and low (2.60kg less) shedding lambs pre-slaughter as well as lower
      dressing% (2.7% lower in high shedding lambs post-weaning). Cryptosporidium (all
      species) shedding pre-slaughter was associated with reduced dressing% in both
      high (1.25% lower) and low (1.21% lower) shedding lambs. Giardia shedding pre
      slaughter was associated with 0.59kg less HSCW in high shedding lambs. Increased
      frequency of C. parvum and Giardia shedding in a specific animal (repeated
      detection) were associated with reduced HSCW and dressing%. Concurrent Giardia
      and Cryptosporidium shedding pre-slaughter was associated with reduced dressing%.
      No statistically significant main effects for either WEC (P>0.05) or Haemonchus
      status (P>0.05) were identified for any of the sheep meat productivity measures
      (live weight, HSCW and dressing%). The findings suggest naturally acquired
      Cryptosporidium and Giardia infections in grazing sheep are associated with
      depressed growth, carcase weight and dressing efficiency beyond the neonatal
      period in sheep representing a range of genetic backgrounds and different sheep
      production environments.

PMID- 27692330
TI  - A growing degree-day model for determination of Fasciola hepatica infection risk
      in New Zealand with future predictions using climate change models.
AB  - Infections of ruminants with Fasciola hepatica are considered to be of regional
      importance within New Zealand but there is very little recent information on its
      prevalence or severity other than anecdotal reports. Generally they are
      considered to be of secondary importance compared to gastrointestinal nematode
      infections. Utilizing data from Virtual Climate Stations (n=11491) distributed on
      a 5km grid around New Zealand a growing degree-day model was used to describe the
      risk of infection with liver fluke from 1972 to 2012 and then to apply the
      predictions to estimate the risk of fluke infections within New Zealand for the
      years 2040 and 2090. The growing degree-day model was validated against the most
      recent survey of infection within New Zealand in 1984. A strong positive linear
      relationship for 1984 between F. hepatica prevalence in lambs and infection risk
      (p<0.001; R2=0.71) was found indicating the model was effective for New Zealand.
      A linear regression for risk values from 14 regions in New Zealand for 1972-2012
      did not show any discernible change in risk of infection over this time period
      (p>0.05). Post-hoc comparisons indicate the risk in Westland was found to be
      substantially higher (p<0.05) than all other regions with Northland ranked second
      highest. Notable predicted changes in F. hepatica infection risk in 2040 and 2090
      were detected although they did vary between different climate change scenarios.
      The highest average percentage changes in infection risk were found in regions
      with low initial risk values such as Canterbury and Otago; in these regions 2090
      infection risk is expected to rise by an average of 186% and 184%, respectively.
      Despite the already high levels of infection risk in Westland, values are
      expected to rise by a further 76% by 2090. The model does show some areas with
      little change with Taranaki predicted to experience only very minor increases in
      infection risk with average 2040 and 2090 predicted changes of 0% and 29%,
      respectively. Overall, these results suggest the significance of F. hepatica in
      New Zealand farming systems is probably underestimated and that this risk will
      generally increase with global warming following climate change.

PMID- 27692331
TI  - First study about the development of adult Echinococcus canadensis G6 genotype of
      goat origin in experimentally infected dogs.
AB  - Echinococcus granulosus sensu lato (E. granulosus sl) must be considered as a
      species complex, comprising Echinococcus granulosus sensu stricto (E. granulosus
      ss, genotypes G1-G3), Echinococcus equinus (G4), Echinococcus ortleppi (G5) and
      Echinococcus canadensis (G6-G10) although the species status of E. canadensis is
      still controversial. These genotypes closely match the intermediate hosts
      associated strains described in earlier times among which E. canadensis G6
      corresponds to the camel strain. As there are no studies concerning the
      development of adult stages of the G6 genotype from non-camel origin, the aims of
      the present study were: to characterize for the first time the development of E.
      canadensis G6 in dogs experimentally infected with protoscoleces derived from
      goats, to describe the resultant adult morphology, to evaluate the growth of
      their rostellar hooks from larval to adult stages and to determine the prepatent
      period of the strobilar stage of E. canadensis G6 derived from goats. The
      development of the strobilar stage of E. canadensis G6 genotype of goat origin
      was examined by studying the growth (variation of the total worm length) and
      segmentation in experimentally infected dogs at 14, 25, 35 and 56days post
      infection. A morphological characterization of 35-day-old worms as well as of
      larval and adult rostellar hooks was also carried out by conventional optical
      microscopic observations and/or by scanning electron microscopy. The prepatent
      period of the strobilar stage was assessed by microscopic examination of faeces
      from 2 infected dogs. Our results were compared with published data from the
      camel and other strains. The roles of the host, genotype and species in
      morphological and developmental features as well as the taxonomic position of E.
      canadensis G6 were discussed. The prepatent period of E. canadensis G6 genotype
      of goat origin was determined as at least, 41days. The obtained results
      contribute to increase the knowledge about the biology and genetics of E.
      granulosus sl complex and are also of practical usefulness for the design of
      disease control strategies.

PMID- 27692332
TI  - Acaricidal efficacies of Lippia gracilis essential oil and its phytochemicals
      against organophosphate-resistant and susceptible strains of Rhipicephalus
      (Boophilus) microplus.
AB  - Plant-derived natural products can serve as an alternative to synthetic compounds
      for control of ticks of veterinary and medical importance. Lippia gracilis is an
      aromatic plant that produces essential oil with high content of carvacrol and
      thymol monoterpenes. These monoterpenes have high acaricidal activity against
      Rhipicephalus (Boophilus) microplus. However, there are no studies that show
      efficacy differences of essential oils between susceptible and organophosphate
      resistant strains of R. (B.) microplus. The aim of the present study was to
      compare acaricidal effects of essential oils extracted from two different
      genotypes of L. gracilis and the main monoterpenes on larvae of both susceptible
      and organophosphate resistant R. (B.) microplus larvae. The efficacy of the
      essential oil of two genotypes of L. gracilis (106 and 201) and their
      monoterpenes carvacrol and thymol was measured using the larval immersion test on
      coumaphos-resistant and susceptible strains of R. (B.) microplus. Lethal
      concentrations were calculated using GraphPad Prism 6.0. Chemical analysis was
      performed by GC-MS and FID. Thymol and carvacrol were observed to be major
      constituents in 106 and 201L. gracilis genotype essential oils, respectively.
      Essential oils of both genotypes were more effective against organophosphate
      resistant tick strain than susceptible tick strain. Carvacrol was 3.2 times more
      toxic to organophosphate resistant strain than to susceptible strain. Thymol was
      equally toxic to resistant and susceptible tick strains. The significantly higher
      efficacy monoterpene carvacrol against resistant ticks may lead to development of
      new natural product acaricide formulations for use to control organophosphate
      resistant R. (B.) microplus populations.

PMID- 27692334
TI  - Erratum to "Prevalence and molecular characterization of Cryptosporidium spp. and
      Giardia duodenalis in dairy cattle in Beijing, China" [Vet. Parasitol. 219 (2015)
      61-65].

PMID- 27692333
TI  - First detection of Leishmania kDNA in canine cerumen samples by qPCR.
AB  - Nowadays, searching for alternative non-invasive methods for molecular diagnosis
      of canine visceral leishmaniosis is getting increasingly important. We previously
      described the presence of Leishmania kinetoplast DNA (kDNA) in canine hair; in
      this case we hypothesized whether foreign DNA might be present in cerumen of dogs
      with leishmaniosis, and be detected by Real time quantitative PCR (qPCR). A
      population of 38 dogs that lived in Leishmania endemic areas was divided in two
      groups: A (33 dogs with confirmed leishmaniosis by serological techniques) and B
      (5 healthy dogs). Blood, lymph node, bone marrow and cerumen samples from all
      animals were tested for the presence of parasite kDNA. Our method was 100%
      specific, and in dogs from group A, Leishmania infantum kDNA was detected and
      quantified in the 100% of lymph node samples, in 90.9% of cerumen samples, in
      88.5% of the bone marrow samples and in 57.6% of the blood samples. The qPCR
      cerumen is a new non-invasive method that shows a high potential for the
      diagnosis of zoonotic visceral leishmaniosis.

PMID- 27692335
TI  - Thymus vulgaris L. essential oil and its main component thymol: Anthelmintic
      effects against Haemonchus contortus from sheep.
AB  - Haemonchus contortus is an important gastrointestinal parasite on sheep farms in
      tropical regions. The resistance of the parasite against most anthelmintic drugs
      represents a great economic problem to sheep farming and is a major challenge
      that needs to be overcome. The searches for new anthelmintic agents that act on
      different stages of the parasite's life cycle are necessary for the development
      of new therapeutic options. The aim of this study was to evaluate the in vitro
      and in vivo anthelmintic activity of Thymus vulgaris essential oil against H.
      contortus and of its main component, the monoterpene thymol. Despite the relative
      ineffectiveness of the oil in the in vivo test, which may be corrected in the
      future after technical improvements to increase the oil's bioavailability, the in
      vitro results validated the popular use of T. vulgaris oil as an anthelmintic
      agent, at least against H. contortus. In fact, both the essential oil and thymol,
      which accounts for 50.22% of the oil composition, were effective against the
      three main stages of H. contortus. The oil and thymol were able to inhibit egg
      hatching by 96.4-100%, larval development by 90.8-100%, and larval motility by 97
      100%. Similar to the positive control (levamisole 20mg/mL), the oil and thymol
      completely inhibited the motility of H. contortus adults within the first 8h of
      the experiment. Since thymol reproduces the anthelmintic effects of the oil and
      because it is the main component of the oil, it is reasonable to assume that
      thymol is the most important compound responsible for the anthelmintic effect of
      T. vulgaris. These results are of ethnopharmacological importance and may
      contribute to the development of new drugs and even herbal medicines, increasing
      treatment options for the farm breeding.

PMID- 27692336
TI  - Ticks threatening lineage of Anatolian wild sheep (Ovis gmelinii anatolica) and
      determination of their tick-borne pathogens.
AB  - We aimed to determine the ticks of the Anatolian wild sheep and to define their
      tick-borne pathogens while molecularly studying their relationships with those of
      the domestic sheep. Furthermore, another aim of this study is to investigate tick
      paralysis resulting in the death of the Anatolian wild sheep. Ticks and blood
      samples were collected from the wild sheep whilst tick samples were also
      collected from hares, guinea fowls, chickens, and a turkey living in the
      Anatolian wild sheep breeding area. While PCR amplification was carried out for
      the detection of Babesia spp., Theileria spp. and Anaplasma spp. in blood
      samples, CCHF virus was screened in the tick samples in addition to the above
      mentioned pathogens. Theileria spp. was detected in blood samples of 45 wild
      sheep. A total of 3494 ticks were collected from 52 Anatolian wild sheep, 5
      hares, 5 guinea fowls, 2 chickens, and 1 turkey whereas 98 ticks were collected
      from the ground. B. ovis and T. ovis were detected in tick pools (Rh. bursa and
      H. excavatum) that were collected from the wild sheep. The paralysis was
      diagnosed in both of the hind legs of the newborn lambs infested with a great
      number of ticks. We also report that the tick species (H. excavatum and Rh.
      bursa) are determined to cause tick paralysis and tick toxicosis, which are
      associated with mortality especially in lambs. T. ovis and B. ovis were detected
      and studied for the first time in Anatolian wild sheep and in their ticks. The
      results of phylogenetic analyses showed that T. ovis and B. ovis isolates are
      genetically very close to the isolates that were previously obtained from the
      domestic small ruminants. We show that the Anatolian wild sheep can play the role
      of a reservoir for T. ovis. The presence of the CCHF virus has also been clearly
      shown and it has been observed that this virus, which is very pathogenic for
      humans, is anywise circulating in the region.

PMID- 27692337
TI  - The usefulness of direct agglutination test, enzyme-linked immunosorbent assay
      and polymerase chain reaction for the detection of Toxoplasma gondii in wild
      animals.
AB  - The aim of the study was to compare the usefulness of two antibody-based methods,
      the direct agglutination test (DAT) and enzyme linked immuosorbent assay (ELISA),
      with that of the polymerase chain reaction (PCR) for detecting anti-Toxoplasma
      gondii in samples derived from naturally-infected wild animals. Antibodies
      against T. gondii were detected in meat juice samples collected from 129 free-
      living carnivores and omnivores. T. gondii seroprevalence was confirmed in 73,6%
      of examined samples when DAT and ELISA were used separately, but in only 88,4%
      samples when both immunological tests were used in parallel. PCR results
      confirmed the presence of DNA of the parasite in 24 of all the 129 samples.
      Sixteen samples were classified as positive when all three tests were used. A
      moderate degree of agreement was found between DAT and ELISA (kappa=0.55).
      However, no agreement was found between the molecular and serological tests:
      kappa=-1.75 for DAT versus PCR; kappa=-1.67 ELISA versus PCR. By using both
      serological tests, antibodies against T. gondii were found in 77.5% of red foxes,
      12.5% of badgers, 40% of martens and 8.3% of raccoon dogs. Antibodies against the
      parasite were detected also in one mink, but not in the sample derived from a
      polecat. T.gondii DNA was found in the brain tissue of 20 red foxes, three
      badgers and one raccoon dog. Our studies confirm that ELISA and DAT are suitable
      and reliable techniques for T. gondii antibody detection in meat juice from wild
      animals when serum samples are unavailable. Positive results obtained by
      immunological tests do not always reflect that the host was infected by T.
      gondii. They indicate only a contact with parasite. PCR should be used to confirm
      te presence of DNA from T. gondii.

PMID- 27692338
TI  - Canine and ovine tick-borne pathogens in camels, Nigeria.
AB  - In April 2008, whole blood samples were collected from 36 dromedary camels in
      Sokoto, North-western Nigeria. Following PCR and reverse line blotting, twenty
      two samples (61%) resulted positive for Ehrlichia/Anaplasma spp. and three (8%)
      for Theileria/Babesia spp., with three (8%) cases of co-infections being found.
      Both sequence and BLAST analyses identified Ehrlichia/Anaplasma spp. and
      Theileria/Babesia spp. positive cases as Anaplasma platys and Theileria ovis,
      respectively. This is the first report of the detection of A. platys and T. ovis
      in camels from sub-Saharan Africa. The epidemiological relevance of this finding
      is enhanced by the close living of these animals with both dogs and small
      ruminants. The high prevalence detected for A. platys suggests a possible role of
      camels as carriers of this infection.

PMID- 27692339
TI  - The white-nosed coati (Nasua narica) is a naturally susceptible definitive host
      for the zoonotic nematode Angiostrongylus costaricensis in Costa Rica.
AB  - Angiostrongylus costaricensis (Strongylida, Angiostrongylidae) is a roundworm of
      rodents, which may cause a severe or fatal zoonosis in several countries of the
      Americas. A single report indicated that the white-nosed coati (Nasua narica),
      acts as a potential free-ranging wildlife reservoir. Here we investigated the
      prevalence and features of A. costaricensis infection in two procyonid species,
      the white-nosed coati and the raccoon (Procyon lotor) from Costa Rica to better
      understand their possible role in the epidemiology of this zoonotic infection.
      Eighteen of 32 (56.2%) white-nosed coatis collected between July 2010 and March
      2016 were infected with A. costaricensis but none of 97 raccoons from the same
      localities were diagnosed with this infection. First-stage larvae of A.
      costaricensis were obtained from feces of 17 fresh white-nosed coati carcasses by
      Baermann technique. Parasite identity was confirmed by morphology, histology and
      molecular characterization of target genes. These data demonstrate that the white
      nosed coati is a naturally susceptible definitive host for A. costaricensis in
      Costa Rica contrary to findings in the raccoon.

PMID- 27692340
TI  - In vitro study of anti-coccidial activity of essential oils from indigenous
      plants against Eimeria tenella.
AB  - This study was designed to evaluate the in vitro anticoccidial properties against
      Eimeria tenella of different essential oils and their major active components.
      Efficacy of ten essential oils from different Thai indigenous plants were
      preliminarily screened and only those with potential were further tested for
      effective concentrations and identifying their active compounds. Oocysticidal
      property was evaluated in term of sporulation inhibition of oocysts and the
      percentage of unsporulated, sporulated and degenerated oocysts, after treatment
      with 125MUg/ml of the selected essential oil, the sample was enumerated by
      haemocytometer, while coccidiocidal activity was assessed by the inhibition of
      sporozoite invasion in MDBK cell lines. Results showed that only Boesenbergia
      pandurata and Ocimum basilicum essential oils had strong sporulation inhibition
      activity by providing a higher ratio of degenerated oocysts and their IC50 were
      0.134 and 0.101mg/ml, respectively. GC-MS analysis of B. pandurata essential oil
      found trans-b-ocimene, camphor, 1,8-cineole, geraniol, camphene, methyl
      cinnamate, l-limonene and linalool as the major components, while methyl
      chavicol, alpha-bergamotene, 1,8-cineole and trans-beta-ocimene were the main
      compounds of O. basilicum essential oil. Methyl cinnamate and camphor were the
      active components of B. pandurata oil, whereas methyl chavicol was the active
      component of O. basilicum oil by exhibiting the oocysticidal effect against E.
      tenella with IC50 values of 0.008, 0.023 and 0.054mg/ml, respectively.
      Furthermore, B. pandurata and O. basilicum oils also showed a strong cytotoxic
      property against coccidia with more than 70% inhibition of sporozoite invasion in
      MDBK cell lines, and their IC50 were 0.004 and 0.004mg/ml, respectively. Methyl
      cinnamate as well as camphor from B. pandurata and methyl chavicol from O.
      basilicum were also effective with IC50 values of 0.029, 0.023, and 0.022mg/ml,
      respectively.

PMID- 27692341
TI  - Primary psoas abscess caused by group A streptococcus in a child: Case report
      with microbiologic findings.
AB  - Primary abscess of the iliopsoas muscle in children is uncommon, especially due
      to Streptococcus pyogenes (group A streptococcus: GAS), which causes a variety of
      diseases ranging from pharyngitis to invasive life-threatening infection. We
      present primary iliopsoas abscess in a nine-year-old boy presenting with fever,
      mild disturbance of consciousness, limp, and pain in the right loin. Magnetic
      resonance imaging and isolation of GAS from both blood and abscess samples led us
      to the confirmative diagnosis. The patient recovered after treatment comprising
      drainage and intravenous antibiotics. The CovRS system is one of the best
      characterized systems with two-component signal transduction in the GAS, and
      mutations in covRS induce overproduction of various virulence factors that play a
      crucial role in invasive GAS infection. RopB, also known as a GAS regulator,
      influences the expression of multiple regulatory networks to coregulate virulence
      factor expression in GAS. In the present case, sequence analysis revealed the
      isolated GAS as emm type 6 with alterations in covS, whereas the covR and ropB
      genes were intact. The covS alterations might have influenced the virulence of
      the strain causing this severe GAS infection.

PMID- 27692342
TI  - Per- and polyfluoroalkyl substances (PFASs) - New endocrine disruptors in polar
      bears (Ursus maritimus)?
AB  - Per- and polyfluoroalkyl substances (PFASs) are emerging in the Arctic and
      accumulate in brain tissues of East Greenland (EG) polar bears. In vitro studies
      have shown that PFASs might possess endocrine disrupting abilities and therefore
      the present study was conducted to investigate potential PFAS induced alterations
      in brain steroid concentrations. The concentrations of eleven steroid hormones
      were determined in eight brain regions from ten EG polar bears. Pregnenolone
      (PRE), the dominant progestagen, was found in mean concentrations of 5-47ng/g
      (ww) depending on brain region. PRE showed significantly (p<0.01) higher
      concentrations in female compared to male bears. Dehydroepiandrosterone (DHEA)
      found in mean concentrations 0.67-4.58ng/g (ww) was the androgen found in highest
      concentrations. Among the estrogens estrone (E1) showed mean concentrations of
      0.90-2.21ng/g (ww) and was the most abundant. Remaining steroid hormones were
      generally present in concentrations below 2ng/g (ww). Steroid levels in brain
      tissue could not be explained by steroid levels in plasma. There was however a
      trend towards increasing estrogen levels in plasma resulting in increasing levels
      of androgens in brain tissue. Correlative analyses showed positive associations
      between PFASs and 17alpha-hydroxypregnenolone (OH-PRE) (e.g. perflouroalkyl
      sulfonates (?PFSA): p<0.01, r=0.39; perfluoroalkyl carboxylates (?PFCA): p<0.01,
      r=0.61) and PFCA and testosterone (TS) (?PFCA: p=0.03, r=0.30) across brain
      regions. Further when investigating correlative associations in specific brain
      regions significant positive correlations were found between ?PFCA and several
      steroid hormones in the occipital lobe. Correlative positive associations between
      PFCAs and steroids were especially observed for PRE, progesterone (PRO), OH-PRE,
      DHEA, androstenedione (AN) and testosterone (TS) (all p<=0.01, r>=0.7). The
      results from the present study generally indicate that an increase in PFASs
      concentration seems to concur with an increase in steroid hormones of EG polar
      bears. It is, however, not possible to determine whether alterations in brain
      steroid concentrations arise from interference with de novo steroid synthesis or
      via disruption of peripheral steroidogenic tissues mainly in gonads and feedback
      mechanisms. Steroids are important for brain plasticity and gender specific
      behavior as well as postnatal development and sexually dimorph brain function.
      The present work indicates an urgent need for a better mechanistic understanding
      of how PFASs may affect the endocrine system of polar bears and potentially other
      mammal species.

PMID- 27692343
TI  - How to manage a pregnant woman for emergency care, anesthesia or intensive care?
      Take home messages from the French Society of Anesthesiology and Intensive Care
      (SFAR) monothematic one-day meeting.

PMID- 27692345
TI  - Is a pediatrician performed gray scale ultrasonography with power Doppler study
      safe and effective for triaging acute non-perforated appendicitis for
      conservative management?
AB  - PURPOSE: The purpose of this study was to examine whether acute non-perforated
      appendicitis (ANPA) can be safely triaged by a pediatrician for conservative
      management (CM) using gray-scale ultrasonography with power Doppler (GSPD).
      METHOD: Seventy five cases of ANPA assessed by a pediatrician with GSPD (2013
      2015) were reviewed. GSPD grading for ANPA was: I: slightly irregular wall/normal
      blood flow; II: irregular wall/increased blood flow; III: irregular
      wall/decreased blood flow; and IV: absence of wall/blood flow. Grades I/II were
      managed conservatively with intravenous antibiotics then encouraged to book for
      interval appendectomy (IA). Grades III/IV were reviewed for emergency
      appendectomy (EA) by a pediatric surgeon. RESULTS: GSPD grading was I (n=26), II
      (n=36), III (n=9), and IV (n=4). EA was required for 5 cases, one grade III, and
      four grade IV cases. One grade IV case was treated conservatively after surgical
      review but EA was unavoidable. Of the remaining 70 cases discharged well after a
      mean of 5.7days hospitalization, 25/70 had IA with chronic inflammation on
      histology, 6/70 had recurrence of ANPA treated successfully by EA, and 39/70
      remain asymptomatic at least 10months after declining IA. Overall, GSPD triaging
      with CM was cheaper than surgery. CONCLUSIONS: GSPD performed by pediatricians
      appears to be safe/effective for triaging ANPA. LEVEL OF EVIDENCE: Level III.

PMID- 27692344
TI  - Autophagy inhibition upregulates CD4+ tumor infiltrating lymphocyte expression
      via miR-155 regulation and TRAIL activation.
AB  - Chemoresistance is a major challenge in lung cancer treatment. Recent findings
      have revealed that autophagic mechanism contributes significantly to
      immunosuppressive related chemoresistance. For that reason, targeting autophagy
      related immunosuppression is an important approach to reverse tumor drug
      resistance. In this study, we report for the first time that autophagy inhibition
      triggers upregulation of CD4+, Foxp3+ tumor infiltrating lymphocytes in late
      metastatic lung cancer tissues. Furthermore, autophagy blockage induces
      chemosensitization to carboplatin, immune activation and cell cycle arrest. This
      induction correlated with reduction in expression of drug resistance genes MDR1,
      MRP1, ABCG2 and ABCC2 along with decreased expression of PD-L1 which is
      associated with severe dysfunction of tumor specific CD8+ T cells. Furthermore,
      experiments revealed that co-treatment of carboplatin and autophagy inhibitor
      chloroquine increased lung tissue infiltration by CD4+, FoxP3+ lymphocytes and
      antigen-specific immune activation. Subsequent ex vivo experiments showed the
      activation of carboplatin related TRAIL-dependent apoptosis through caspase 8 and
      a synergistic role of miR-155 in lung tissue infiltration by CD4+, and FoxP3+
      lymphocytes. Overall, our results indicate that autophagy blockage increases lung
      cancer chemosensitivity to carboplatin, but also reveal that miR-155 functions as
      a novel immune system activator by promoting TILs infiltration. These results
      indicate that targeting of autophagy can prevent cancer related immunosuppression
      and elucidate immune cell infiltration in tumor microenvironment thus
      representing a potential therapeutic strategy to inhibit lung cancer progression
      and metastasis.

PMID- 27692346
TI  - The operative management of children with complex perianal Crohn's disease.
AB  - BACKGROUND/PURPOSE: Perianal Crohn's disease (PCD) can affect both quality of
      life and psychological wellbeing. A subset of pediatric patients with complex PCD
      require surgical intervention, although appropriate timing and treatment regimens
      remain unclear. This study aimed to describe a large pediatric cohort in a
      tertiary center to determine the range of surgical management in children with
      complex PCD. METHODS: A retrospective review of children requiring operative
      intervention for PCD over 13 years (2002-2014) was performed. PCD was divided
      into simple and complex based on the type of surgical procedure, and the two
      groups were compared. RESULTS: The 57 children were divided into two groups: the
      simple group (N=43) underwent abscess drainage +/- seton insertion alone, and the
      complex group (N=14) underwent loop ileostomy +/- more extensive surgery. In the
      complex group, females were more predominant (57% of complex vs 30% of simple),
      and the average age at diagnosis was lower. Anti-TNF therapy was utilized in
      79.1% of simple and 100% of complex PCD. All 14 complex patients underwent a
      defunctioning ileostomy, with 7 requiring further operations (subtotal
      colectomy=4, proctocolectomy +/- anal sparing=5, plastic surgery reconstruction
      with perineal flap/graft=4). CONCLUSION: Complex PCD represents a small but
      challenging subset of patients in which major surgical intervention may be
      necessary to alleviate the symptoms of this debilitating condition. LEVEL OF
      EVIDENCE: retrospective case study with no control group - level IV.

PMID- 27692347
TI  - Don't forget the dose: Improving computed tomography dosing for pediatric
      appendicitis.
AB  - BACKGROUND: A pediatric computed tomography (CT) radiation dose reduction program
      was implemented throughout our children's associated hospital system in 2010. We
      hypothesized that the CT dose received for evaluation of appendicitis in children
      would be significantly higher among the 40 referral, nonmember hospitals (NMH)
      than the 9 member hospitals (MH). METHODS: Preoperative CTs of pediatric
      (<18years) appendectomy patients between April 2012 and April 2015 were reviewed.
      Size specific dose estimate (SSDE), an approximation of absorbed dose
      incorporating patient diameter, and Effective Dose (ED) were calculated for each
      scan. RESULTS: 1128 (65%) of 1736 appendectomy patients underwent preoperative
      CT. 936 patients seen at and 102 children evaluated at NMH had dosing and patient
      diameter data for analysis. SSDE and ED were significantly higher with greater
      variance at NMH across all ages (all p<0.05, Figure). NMH's SSDE and ED also
      exceeded reference levels. CONCLUSION: Radiation exposure in CT scans for
      evaluation of pediatric appendicitis is significantly higher and more variable in
      NMH. A proactive approach to reduce dose, in addition to frequency, of CT scans
      in pediatric patients is essential. LEVEL OF EVIDENCE: Level III.

PMID- 27692348
TI  - [Follow-up interventions after suicide attempt. What tools, what effects and how
      to assess them?]
AB  - After attempting suicide, 60 to 70% of patients are discharged from emergency
      departments and referred to outpatient treatment which entails psychosocial
      strategies, pharmacological strategies or a combination. The main objective of
      outpatient care consists in preventing recurrent suicidal behavior. Yet suicide
      attempters have been found to be very difficult to engage in treatment. Between
      11% and 50% of attempters refuse outpatient treatment or drop out of outpatient
      therapy very quickly. In order to address this extremely serious issue, for the
      past 20 years monitoring or follow up interventions has been presented as a
      promising approach. Follow-up intervention is defined as a service that aims at
      both increased access to and engagement in care as well as to prevent suicide and
      related behaviors. This approach consists in "stay in contact" or "connectedness"
      protocols using phone calls or tele-assistance, sending letters, email or mobile
      phone messages and medical visits or nursing at home. From one study to another
      these tools have been used separately, associated to one another or reinforced by
      motivational interviewing or brief psychotherapy. To our knowledge, since 1993 16
      controlled and randomized controlled studies assessed the effectiveness of
      diverse follow-up. Four studies assessing telephone follow up reported a
      significant decrease in suicide reattempt while one study evaluating a sending
      letters strategy reported positive results. Among five studies assessing
      engagement in healthcare, only two (one using phone follow up and the other
      sending letters reported significantly positive results. The refusal rate of
      monitoring strategies has not exceeded 11% attesting to the high applicability of
      these methods. Despite several positive results, we cannot draw firm conclusions
      on replicability of these results. This is largely due to methodological issues:
      lack of standardization of interventions, lack of consensus on definition of the
      main measured variables (recurrent suicidal behavior, engagement in healthcare)
      but also to the confounding effect of other care approaches frequently associated
      with follow up intervention services. Further studies and research should be
      conducted as follow-up intervention services are increasingly used in suicide
      prevention because of their good acceptability and usefulness.

PMID- 27692349
TI  - [Validation of a French translation of Krueger's personality inventory for DSM-5
      in its brief form (PID-5 BF)].
AB  - OBJECTIVE: Since the publication of the DSM-5 (APA, 2013), the dimensional
      conception of the personality disorders is co-existing with the classical
      categorical paradigm. Tools have been proposed for the evaluations of five big
      pathological factors to be explored further according to the APA (negative
      affectivity, detachment, antagonism, disinhibition, psychoticism). Despite
      numerous works using these questionnaires (30 works in 3 years according to Al
      Adjani et al., 2015), none of them have yet been translated into French. Also,
      the main objective of the paper is to present a French translation of the
      Personality Inventory for DSM -5 by Kruegger et al. (2013) in its brief form of
      25 items (PID-5 BF). METHOD: To reach this goal, we have employed the classic
      translation-retranslation method (Vallerand, 1989) and tested the consistence and
      the validity of this French version among a non-clinical sample (n=216) of young
      adults (age=31.4, SD=4.8), in joining some other questionnaires in their short
      forms to study the external validity of the PID-5 about the psychological
      distress (SCL-10, Nguyen, 1983), the categorical diagnosis of personality
      disorders (SAPAS, Moran et al., 2003) and the classical Big Five dimensions of
      the personality (BDI 10, Ramamstedt and John, 2007). The internal consistency of
      this translation has been studied through the classical outcomes on factor
      analysis for the dimensional repartitions of the items in 5 scales and Cronbach's
      alpha for the consistency of each found dimensions. The external validity has
      been explored by studying Pearson's correlations between the outcomes on each
      dimension of the PID-5 BF and both the clinical dimensions of SCL-10, personality
      dimensions of the BFI-10 or personality disorders (SAPAS). RESULTS: Factor
      analysis led to the same repartition of the 25 items as the original versions.
      Each of the dimensions is consistent enough (alpha>.65) to be taken into account
      as clinically significant. The items of the French version of the PID-5 BF follow
      the expected repartitions in 5 dimensions, which are consistent enough. Although
      their mean scores are significantly not different from the outcomes found by
      Krueger with the PID-5 200 items among another non-clinical population (n=264),
      one cannot say that is enough to ensure the external validity of our translation,
      for it uses neither the same tools nor sample. A comparison with a French
      translation of the PID-5 would be more significant. However, the external
      validity of the French version seems to be significant enough. Global score on
      the PID-5 is correlated both to the Global Severity Index of the SCL-10, which
      reflects global psychological distress, and SAPAS's score, which evaluates the
      suspicion of personality disorder. The clinical validity of the PID-5 is
      confirmed by the relationships between negative affectivity and anxiety or
      depression or antagonism and hostility, although the clinical scale of the SCL
      10, with one item by dimension, is less sensitive than the complete original
      version in 90 items (DeRogatis, 1974). PID-5 score and domains are also
      correlated with the Big Five personality dimension and global score of
      personality disorders which led us to think that it is coherent with the
      evaluation of personality suffering (r=.34) and dimensions. The links between
      negative affectivity and neurosism (r=.48) or between desinhibition and
      extraversion (r=.32) or the negative correlation between psychoticism and
      conscientiousness (r=-0.16) are consistent with the expectations related both to
      the descriptions of the domains by the DSM and outcomes on the comparisons
      between PID-5 200 item scales and NEO-PI or BFI 45 items. DISCUSSION: This
      translation offers enough consistency and validity to be used in future studies.
      This could lead us to either continue studying a more representative general
      population or testing its validity in focusing on a clinical sample where
      personality disorders are prevalent, such as homeless men or substance users. As
      soon as a French version of the PID-5 200 items is published, one can compare the
      outcomes on PID-5 BF and PID-5 to lead to estimations of personality disorders
      and pathological domains among French populations and explore personality
      disorders throughout a dimensional paradigm instead of syndromic perspective. One
      can also see whether the items that have been kept for each dimension are as
      saturated in the French version as in the original one. Among general
      populations, comparisons with clinical distress, syndromic personality disorders
      or dimensional aspect of personality could be done with complete versions of PID
      5, Symptom Check-list, Personality Disorders Questionnaires or Big Five
      Inventory; therefore, the brief forms of any questionnaire could be used among
      any people whose psychological distress or side effects impaired their attention
      and concentration.

PMID- 27692350
TI  - [Epigenetics' implication in autism spectrum disorders: A review].
AB  - BACKGROUND: The etiology of autism spectrum disorders (ASD) is complex and
      multifactorial, and the roles of genetic and environmental factors in its
      emergence have been well documented. Current research tends to indicate that
      these two factors act in a synergistic manner. The processes underlying this
      interaction are still poorly known, but epigenetic modifications could be the
      mediator in the gene/environment interface. The epigenetic mechanisms have been
      implicated in susceptibility to stress and also in the pathogenesis of
      psychiatric disorders including depression and schizophrenia. Currently, several
      studies focus on the consideration of the etiological role of epigenetic
      regulation in ASD. OBJECT: The object of this review is to present a summary of
      current knowledge of an epigenetic hypothesis in ASD, outlining the recent
      findings in this field. METHODS: Using Pubmed, we did a systematic review of the
      literature researching words such as: autism spectrum disorders, epigenetics, DNA
      methylation and histone modification. RESULTS: Epigenetic refers to the molecular
      process modulating gene expression without changes in the DNA sequence. The most
      studied epigenetic mechanisms are those that alter the chromatin structure
      including DNA methylation of cytosine residues in CpG dinucleotides and post
      translational histone modifications. In ASD several arguments support the
      epigenetic hypothesis. In fact, there is a frequent association between ASD and
      genetic diseases whose epigenetic etiologies are recognized. A disturbance in the
      expression of genes involved in the epigenetic regulation has also been described
      in this disorder. Some studies have demonstrated changes in the DNA methylation
      of several autism candidate genes including the gene encoding the oxytocin
      receptor (OXTR), the RELN and the SHANK3 genes. Beyond the analysis of candidate
      genes, recent epigenome-wide association studies have investigated the
      methylation level of several other genes and showed hypomethylation of the whole
      DNA in brain and blood samples of autistic patients. The changes in epigenetic
      marks following exposure to environmental factors known as autism risk factors
      are also discussed in many reports. They include nutritional (vitamin D and
      folate) and toxic (sodium valproate, bisphenol A) factors. Despite a considerable
      contribution to understanding the complexity of ASD etiology, the epigenetic
      studies suffer from numerous methodological biases that limit the scope of their
      results and make their interpretation difficult. The cell samples used in the
      psychiatric studies are mostly from the post-mortem tissue of the central nervous
      system, and factors that might change the epigenome (age, gender, treatments
      received...) are not taken into account. The use of blood and buccal epithelium
      samples raises in turn the question as to whether the epigenome of these cells
      reflects that of the nerve cells. DNA methylation can also be influenced by cell
      subcomposition variability, transcriptional variability and by DNA sequence
      variants. CONCLUSION: These recent discoveries in epigenetics are the beginnings
      of an etiopathogenic research revolution in neurodevelopmental disorders. The
      conceptualization of epigenetic processes is in its early stages and despite its
      limited means will help integrate disparate data factors previously involved in
      autism. It could also be the target for the development of new therapeutic
      modalities.

PMID- 27692352
TI  - Editors' Note.

PMID- 27692351
TI  - Azithromycin assay in drug formulations: Validation of a HPTLC method with a
      quadratic polynomial calibration model using the accuracy profile approach.
AB  - Many different assaying high performance thin layer chromatography (HPTLC)
      methods have been developed and validated in order to be used in routine analysis
      in different analytical fields. Validation often starts by the evaluation of the
      linearity of the calibration curve. Frequently, if the correlation coefficient is
      close to one, the linear calibration curve model is considered to be proper to
      predict the unknown concentration in the sample. But is this simple model
      effective to assess the behavior of the response of an HPTLC method as a function
      of concentration. To answer this question, a method for the determination of
      azithromycin by HPTLC has been developed and validated following both the
      classical approach and that based on the accuracy profile. Silica gel plates with
      fluorescence indicator F254 and chloroform - ethanol - 25% ammonia 6:14:0.2
      (v/v/v) as mobile phase were used. Analysis was carried out in reflectance mode
      at 483nm. The RF of azithromycin was 0.53. The validation based on the classical
      approach, shows that the behavior is not linear, even though r2=0.999 because the
      lack of fit test is significant (P<0.05). Validation based on the accuracy
      profile approach considering both the straight line and the quadratic regression
      model, show that the former results is a beta-expectation tolerance interval
      outside the acceptance limits, while with the latter, this interval is within the
      limits of +/-5% acceptability for a range which extends from 0.2 to 1.0MUg/zone.
      With the quadratic model, the method showed to be precise and accurate.

PMID- 27692353
TI  - Does Donor Status, Race, and Biological Sex Predict Organ Donor Registration
      Barriers?
AB  - PURPOSE: The purpose of the current study was to examine differences among bodily
      integrity, disgust, medical mistrust, and superstition among African Americans,
      Caucasians, and Latinos; females and males; and registered organ donors and non
      registered potential donors. METHODS: A random digit dialing phone survey was
      utilized to garner information pertaining to organ donation beliefs among African
      American (n = 200), Caucasian (n = 200), and Latino (n = 200) Chicago residents.
      More specifically, participants responded to measures of bodily integrity,
      disgust, medical mistrust, and superstition, organ donor registration status,
      among others. RESULTS: The results indicated that African American and Latino
      participants were less likely to be registered organ donors than Caucasians (p <
      .001). In general, females maintained fewer barriers than males with respect to
      bodily integrity (p < .05), disgust (p = .01), and superstition (p = .01). With
      respect to organ donation barriers, bodily integrity (p < .0001) emerged as a
      central concern among those surveyed. CONCLUSION: This study highlights the
      significance of audience segmentation when promoting posthumous organ and tissue
      donation. Specifically, the results stress the importance of constructing
      distinct messages to non-registered potential donors compared to messages
      delivered to registered donors. Moreover, different barriers surfaced among
      females and males as well as among African American, Caucasian, and Latino
      residents. It is clear that a one size fits all approach will likely not work
      when promoting organ and tissue donation.

PMID- 27692354
TI  - Recruitment of Underrepresented Minorities in Medical School Through a Student
      led Initiative.
AB  - The goal of matriculating a diverse medical cohort remains important for
      institutions across the country as it results in an increase in the diversity of
      the physician workforce. By admitting students who are underrepresented in
      medicine, the pressing health needs of the growing and diverse patient population
      of our country can be met by physicians who are representative of their
      communities. Given the challenges of choosing from a small pool of applicants,
      medical schools should consider seeking the support of current medical students
      in expanding the applicant pool and recruiting the next generation of physicians.
      The purpose of this paper is to describe a student-led initiative established at
      the University of Kentucky College of Medicine for recruiting students
      underrepresented in medicine. Through this pipeline program, current
      underrepresented applicants experience a two-day recruitment event that
      introduces them to life as a medical student. Incorporating current medical
      students in recruitment programming allows institutions to access a knowledgeable
      and inspirational resource that is readily available. Current medical students
      can provide firsthand perspectives into the journey that is medical school while
      serving as role models for future physicians.

PMID- 27692355
TI  - Mini-Medical School Programs' Influence on Students' Desire to Pursue Medicine.
AB  - PURPOSE: Mini-Medical school programs have become an increasingly popular means
      of encouraging high-school students to consider medical professions. However,
      there is little research evaluating the long-term effect of these programs on
      influencing career choice. The purpose of our study was to determine the
      motivational factors for attending the Mini-Medical school programs at our
      institution, student satisfaction with their experience, and whether it impacts
      intended secondary education and career choices. METHODS: An online anonymous
      survey was distributed to Drexel University College of Medicine Mini-Medical
      school program graduates to determine factors influencing student participation
      and program satisfaction. RESULTS: The most influential factors in attending the
      program were to confirm an interest in medicine (n = 55, 95%) and parental advice
      (n = 29, 50%). Most maintained an interest in medicine: 57% (n = 33) pursued a
      pre-med degree, 55% (n = 32) planned to apply to medical school within 3 years;
      and 12% (n = 7) were either in medical school or matriculating in the fall of
      2015. 91% (n = 53) participants noted the program's influence on choosing a pre
      med undergraduate track. CONCLUSION: Our results suggest Mini-Medical school
      programs significantly impacted students' decision to pursue a medical career
      through fostering interest and effectively answering students' questions about
      the field.

PMID- 27692356
TI  - Childhood Obesity in an Inner-City Primary Care Population: A Longitudinal Study.
AB  - BACKGROUND: Understanding the dynamics of obesity among children and adolescents
      in high-risk, low-income patient populations is critical to guide and evaluate
      appropriate clinical and public health interventions. METHODS: We identified a
      cohort of 472 predominantly low-income, minority pediatric patients aged 3-18
      years with baseline measurements in 2010 and analyzed follow-up data through
      September 2013. Weight status at baseline and end of follow-up were ascertained.
      RESULTS: The prevalence of obesity was 25% (95% confidence interval [CI] 21%-29%)
      at baseline and 24% (95% CI 20%-28%) after an average of 2.3 years follow-up.
      Among the 353 subjects who were not obese at baseline, the cumulative incidence
      of obesity was 8% (95% CI 5%-11%). Those who were normal weight at baseline had
      an incidence of 3% (1%-6%); those who were overweight had an incidence of 22%
      (95% CI 14%-32%). Among the 119 subjects who were obese at baseline, 29% (95% CI
      21%-38%) were not obese at the end of follow-up. Remission of obesity among those
      who were severely obese was only 12% (95% CI 4%-26%); among other obese patients
      remission was 38% (95% CI 28%-50%). CONCLUSION: The prevalence of obesity did not
      change substantially during follow-up. The cumulative incidence of obesity was
      8%, and most of the incidence was among children who were overweight at baseline.
      Remission was common, especially among those who were not severely obese at
      baseline. Understanding and addressing determinants of obesity over the
      lifecourse is critical to the long-term health of children in the United States.

PMID- 27692357
TI  - Correlation of CAT Score With Peak Expiratory Flow in Acute Exacerbation of COPD
      Patients.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) leads to physical
      activity limitation and a significant reduction in quality of life. This study
      aimed to investigate the correlation between The COPD Assessment Test (CAT) score
      and peak expiratory flow (PEF), and the factors effecting hospital admission
      rates of patients with COPD. METHODS: This observational study was conducted
      prospectively. CAT score was calculated and PEF measured at the time of emergency
      department admission. Descriptive statistics were expressed as number (n),
      percentage (%), and mean +/- standard deviation. Chi-Square and correlation tests
      were used for statistical analyses. A p value of less than 0.05 was considered
      statistically significant. RESULTS: Of 123 patients included in the study, 85
      (69.1%) were male and 38 (30.9%) were female. Pulse pressure, pH, blood urea
      nitrogen, oxygen saturation measured by pulse oximetry (SpO2), PO2, PCO2, and
      SpO2 values on arterial blood gas analysis, and PEF value were significantly
      correlated to CAT score (p < 0.05). CONCLUSION: High CAT score and low PEF value
      can be used to make the decision of hospitalization from emergency department in
      acute exacerbations of COPD.

PMID- 27692358
TI  - Stiff Person Syndrome Masquerading as Acute Coronary Syndrome.
AB  - Stiff person syndrome (SPS) is a rare neuroimmunological disorder characterized
      by severe progressive muscle stiffness in axial and lower extremity musculature
      with superimposed painful muscle spasms. Although chest pain is a common reason
      for SPS patients presenting to the emergency room, this disorder is overlooked
      and not part of the differential diagnosis of chest pain. Herein, we report on a
      middle age male presenting with classic symptoms of SPS; however, due to the
      rarity of this disease, he was initially thought to have acute coronary syndrome.
      Clinicians should consider the diagnosis of SPS in patients with fluctuating
      muscle spasms in the torso and/or extremities in the setting of repeated
      hospitalizations without subsequent symptom relief.

PMID- 27692359
TI  - Surgical Residency Training in Developing Countries: West African College of
      Surgeons as a Case Study.
AB  - BACKGROUND: In 1904, William Halsted introduced the present model of surgical
      residency program which has been adopted worldwide. In some developing countries,
      where surgical residency training programs are new, some colleges have introduced
      innovations to the Halsted's original concept of surgical residency training.
      These include 1) primary examination, 2) rural surgical posting, and 3)
      submission of dissertation for final certification. STUDY DESIGN: Our information
      was gathered from the publications on West African College of Surgeons' (WACS)
      curriculum of the medical schools, faculty papers of medical schools, and
      findings from committees of medical schools. Verbal information was also gathered
      via interviews from members of the WACS. Additionally, our personal experience as
      members and examiners of the college are included herein. We then noted the
      differences between surgical residency training programs in the developed
      countries and that of developing countries. RESULTS: The innovations introduced
      into the residency training programs in the developing countries are mainly due
      to the emphasis placed on paper qualifications and degrees instead of
      performance. CONCLUSION: We conclude that the innovations introduced into
      surgical residency training programs in developing countries are the result of
      the misconception of what surgical residency training programs entail.

PMID- 27692360
TI  - Erratum to "History of the Family Practice Section National Medical Association"
      Journal of the National Medical Association Summer 2015:107(3), Pages 76-77.

PMID- 27692361
TI  - Evaluation of diagnostic methods in equine endometritis.
AB  - This review suggests a classification for uterine diseases of mares. Information
      is presented on the prevalence of endometritis in the past and at present. The
      review describes uterine sampling techniques for mares: swabbing, cytobrushing,
      low volume lavage and biopsy. The performance of culture, cytology and histology
      and threshold values is discussed. Correlations between different diagnostic
      methods and fertility are presented, as well as specificities, sensitivities and
      positive and negative predictive values of the diagnostic methods. The necessity
      for double-guarded techniques is emphasized to prevent sample contamination.

PMID- 27692362
TI  - HIF1A and EPAS1 mRNA and protein expression during in vitro culture of human
      primary term cytotrophoblasts and effect of oxygen tension on their expression.
AB  - During the first trimester of pregnancy, placenta formation probably occurs in a
      low-oxygen environment necessary to protect cytotrophoblasts from oxidative
      stress and to allow proper gene regulation. Transcription factors involved in
      gene regulation under low oxygen tension are the hypoxia-inducible factors,
      mainly HIF1A, EPAS1 and their dimerization partner HIF1B. Little is known about
      their expression during in vitro culture of cytotrophoblasts under chronic
      hypoxia. We assessed HIF1A and EPAS1 expression in a 4-day in vitro culture of
      primary term cytotrophoblasts under 21% O2 and 2.5% O2. Copy numbers and relative
      mRNA expression were assessed by real-time quantitative polymerase chain
      reaction. Protein levels were quantified by immunoblot and densitometric
      analysis. In undifferentiated cytotrophoblasts, EPAS1 transcripts were four times
      more abundant than HIF1A transcripts (2.14e7 and 5e6copies/MUg total RNA,
      respectively). During cell culture, HIF1A mRNA expression increased after 24h and
      then decreased to stay stable. The expression was even lower when cells were
      grown under 2.5% O2. EPAS1 mRNA expression increased during cytotrophoblast
      differentiation. The expression was higher when cells were under 21% O2 than when
      they were under 2.5% O2. Interestingly, HIF1A, but not EPAS1, was detected in the
      nuclei of undifferentiated cytotrophoblasts, and in the nuclei of
      cytotrophoblasts that grew under 21% O2. During cytotrophoblast differentiation,
      no variation in HIF1A protein levels was detected. To the contrary, EPAS1 protein
      level increased during differentiation, and oxygen tension had no effect on EPAS1
      protein level. In conclusion, HIF1A and EPAS1 expression was not inhibited by
      chronic hypoxia during in vitro cytotrophoblast differentiation.

PMID- 27692363
TI  - Exogenous melatonin reduced blood pressure in late-term ovine fetus via MT1/MT2
      receptor pathways.
AB  - Melatonin is involved in the regulation of blood pressure through the receptor
      dependent or independent route. However, the effect of melatonin on fetal blood
      pressure is unknown. This study investigated the effect of melatonin on blood
      pressure of the late-term ovine fetus in utero. Melatonin and/or antagonists were
      intravenously administered into the fetuses. Mean arterial pressure and heart
      rate were recorded. Fetal blood samples were analyzed for biochemical parameters
      and hormones, including cortisol, angiotensin I, angiotensin II, aldosterone,
      atrial natriuretic peptide, corticotrophin-releasing hormone, adrenocorticotropic
      hormone, and endothelin. Fetal blood pressure was decreased following
      administration of melatonin, whereas it was increased following administration of
      luzindole, but not prazosin. Plasma level of endothelin was decreased by
      melatonin, which was blocked by luzindole. Our study suggested that melatonin
      reduced fetal blood pressure via MT1/MT2 receptors and possibly involving release
      of endothelin.

PMID- 27692364
TI  - PLAC1 is involved in human trophoblast syncytialization.
AB  - Placenta specific protein 1 (PLAC1) is thought to be important for murine and
      human placentation because of its abundant expression in placenta; however, the
      trophoblast subtypes that express PLAC1 at the fetomaternal interface and the
      major role of PLAC1 in placentation are still unclear. This study investigated
      the expression pattern of PLAC1 at the human fetomaternal interface and its
      involvement in trophoblast syncytialization. Localization of PLAC1 at the
      fetomaternal interface was studied using in situ hybridization (ISH) and
      immunohistochemistry (IHC) assays. Real time RT-PCR and Western Blot were
      employed to exhibit the expression pattern of PLAC1 during human spontaneous
      syncytialization of term primary cytotrophoblast cells (CTBs). Spontaneous
      syncytialization of a primary term CTBs model transfected with siRNA specific to
      PLAC1 was used to investigate the role of PLAC1 during human trophoblast
      syncytialization. The results showed that PLAC1 was mainly expressed in the human
      villous syncytiotrophoblast (STB) layer throughout gestation, and the expression
      level of PLAC1 was significantly elevated during human trophoblast
      syncytialization. Down-regulation of PLAC1 via specific PLAC1 siRNA transfection
      attenuated spontaneous syncytialization of primary term CTBs (p<0.05) as
      indicated by cell fusion index and the expression patterns of the corresponding
      markers. These data demonstrate the facilitative role of PLAC1 in normal human
      trophoblast syncytialization.

PMID- 27692366
TI  - Effects of Spin-Labels on Membrane Burial Depth of MARCKS-ED Residues.
AB  - Site-directed spin-labeling electron paramagnetic resonance spectroscopy is a
      useful tool to obtain information about the environment of specific residues. One
      of its applications is to investigate membrane protein topology based on the
      accessibility of the spin label, with the assumption that the position of the
      spin label in the membrane is close to that of the native residue. This
      assumption is valid in proteins with well-ordered structures, but could be
      problematic in small peptides because the labeling may cause a perturbation that
      is large enough to change local interactions between the peptide and the
      membrane. To quantitatively characterize such effects, we have simulated the
      association of a 25-amino-acid peptide, MARCKS-ED, to membranes with and without
      spin labels. Our simulations show that the depths of spin labels are ~6-17 A
      deeper than the unlabeled charged and polar residues in the wild-type. When the
      hydrophobic residue Phe is labeled, however, the spin-label depth is close to
      that of the native residue as well as the experimental value. Our study suggests
      that one should be cautious in interpretation of spin label data when charged and
      polar residues in small peptides are labeled.

PMID- 27692365
TI  - Contributions of Microtubule Dynamic Instability and Rotational Diffusion to
      Kinetochore Capture.
AB  - Microtubule dynamic instability allows search and capture of kinetochores during
      spindle formation, an important process for accurate chromosome segregation
      during cell division. Recent work has found that microtubule rotational diffusion
      about minus-end attachment points contributes to kinetochore capture in fission
      yeast, but the relative contributions of dynamic instability and rotational
      diffusion are not well understood. We have developed a biophysical model of
      kinetochore capture in small fission-yeast nuclei using hybrid Brownian
      dynamics/kinetic Monte Carlo simulation techniques. With this model, we have
      studied the importance of dynamic instability and microtubule rotational
      diffusion for kinetochore capture, both to the lateral surface of a microtubule
      and at or near its end. Over a range of biologically relevant parameters,
      microtubule rotational diffusion decreased capture time, but made a relatively
      small contribution compared to dynamic instability. At most, rotational diffusion
      reduced capture time by 25%. Our results suggest that while microtubule
      rotational diffusion can speed up kinetochore capture, it is unlikely to be the
      dominant physical mechanism for typical conditions in fission yeast. In addition,
      we found that when microtubules undergo dynamic instability, lateral captures
      predominate even in the absence of rotational diffusion. Counterintuitively,
      adding rotational diffusion to a dynamic microtubule increases the probability of
      end-on capture.

PMID- 27692367
TI  - [Intractable intraoperative brain herniation secondary to tension pneumocephalus:
      a rare life-threatening complication during drainage of subdural empyema].
AB  - Tension pneumocephalus is rare but has been well documented following trauma and
      neurosurgical procedures. It is a surgical emergency as it can lead to
      neurological deterioration, brainstem herniation and death. Unlike previous cases
      where tension pneumocephalus developed postoperatively, we describe a case of
      intraoperative tension pneumocephalus leading to sudden, massive open brain
      herniation out of the craniotomy site. The possible causative factors are
      outlined. It is imperative to rapidly identify possible causes of acute
      intraoperative brain herniation, including tension pneumocephalus, and institute
      appropriate measures to minimize neurological damage.

PMID- 27692368
TI  - [Difficult fiberoptic tracheal intubation in 1 month-old infant with Treacher
      Collins Syndrome].
AB  - : Neonates and small infants with craniofacial malformation may be very difficult
      or impossible to mask ventilate or intubate. We would like to report the
      fiberoptic intubation of a small infant with Treacher Collins Syndrome using the
      technique described by Ellis et al. CASE REPORT: An one month-old infant with
      Treacher Collins Syndrome was scheduled for mandibular surgery under general
      endotracheal anesthesia. Direct laryngoscopy for oral intubation failed to reveal
      the glottis. Fiberoptic intubation using nasal approach and using oral approach
      through a 1.5 size laryngeal mask airway were performed; however, both approach
      failed because the fiberscope loaded with a one 3.5mm ID uncuffed tube was stuck
      inside the nasal cavity or inside the laryngeal mask airway respectively.
      Therefore, the laryngeal mask airway was keep in place and the fiberoptic
      intubation technique described by Ellis et al. was planned: the tracheal tube
      with the 15mm adapter removed was loaded proximally over the fiberscope; the
      fiberscope was advanced under video-screen visualization into the trachea; the
      laryngeal mask airway was removed, leaving the fiberscope in place; the tracheal
      tube was passed completely through the laryngeal mask airway and advanced down
      over the fiberscope into the trachea; the fiberscope was removed and the 15mm
      adapter was reattached to the tracheal tube. CONCLUSION: The fiberoptic
      intubation method through a laryngeal mask airway described by Ellis et al. can
      be successfully used in small infants with Treacher Collins Syndrome.

PMID- 27692369
TI  - [Tension pneumothorax during peroral endoscopic myotomy for treatment of
      esophageal achalasia under general anesthesia].
AB  - More and more endoscopically gastrointestinal procedures require
      anesthesiologists to perform general anesthesia, such as "peroral endoscopic
      myotomy". Peroral endoscopic myotomy is a novel invasive treatment for the
      primary motility disorder of esophagus, called esophageal achalasia. Despite of
      its minimally invasive feature, there are still complications during the
      procedure which develop to critical conditions and threat patients' lives. Herein
      we describe a case about tension pneumothorax subsequent to esophageal rupture
      during peroral endoscopic myotomy. The emergent management of the complication is
      stated in detail. The pivotal points of general anesthesia for patients
      undergoing peroral endoscopic myotomy are emphasized and discussed. Also,
      intraoperative and post-operative complications mentioned by literature are
      integrated.

PMID- 27692371
TI  - [Paratracheal cyst rupture: a differential diagnosis for tracheal rupture].
AB  - Tracheobronchial rupture is a rare but potentially life-threatening complication
      commonly caused by neck and chest trauma. Iatrogenic tracheobronchial rupture can
      be caused by intubation, tracheostomy, bronchoscopy but also linked to pre
      existing primary diseases. Paratracheal air cysts, infrequently described in
      literature, seem to be associated with obstructive lung disease and weaknesses in
      right posterior lateral wall of the trachea. We report a case of a paratracheal
      air cyst rupture in a previous healthy patient.

PMID- 27692370
TI  - [Effect of dexmedetomidine on acute lung injury in experimental ischemia
      reperfusion model].
AB  - PURPOSE: Ischemia-reperfusion injury is one of the consequences of tourniquet
      application for extremity surgery. The aim of the study was to establish the
      effect of dexmedetomidine on the acute lung injury following lower extremity
      experimental ischemia-reperfusion model in rats. METHODS: Twenty-eight Wistar
      Albino breed rats were recruited after Ethics Committee approval and allocated
      into 4 groups, each with 7 subjects. Group 1 (SHAM) received only anesthesia.
      Group 2 (IR) had experienced 3h of ischemia and 3h of reperfusion using left
      lower extremity tourniquet after anesthesia application. Groups 3 (D-50) and 4 (D
      100) had undergone the same procedures as in the Group 2, except for receiving 50
      and 100mg.kg-1, respectively, dexmedetomidine intraperitoneally 1h before the
      tourniquet release. Blood samples were obtained for the analysis of tumor
      necrosing factor-alpha and interleukin-6. Pulmonary tissue samples were obtained
      for histological analysis. RESULTS: No significant difference regarding blood
      tumor necrosing factor-alpha and interleukin-6 values was found among the groups,
      whereas pulmonary tissue injury scores revealed significant difference.
      Histological scores obtained from the Group 2 were significantly higher from
      those in the Groups 1, 3 and 4 with p-values 0.001 for each comparison. Moreover,
      Group 1 scores were found to be significantly lower than those in the Groups 3
      and 4 with p-values 0.001 and 0.011, respectively. No significant difference was
      observed between the Groups 3 and 4. CONCLUSION: Dexmedetomidine is effective in
      reduction of the experimental ischemia-reperfusion induced pulmonary tissue
      injury in rats, formed by extremity tourniquet application.

PMID- 27692372
TI  - Determination of ultra-trace amounts of prosthesis-related metals in whole blood
      using volumetric absorptive micro-sampling and tandem ICP - Mass spectrometry.
AB  - This paper reports on an evaluation of the suitability of a novel sample
      collection approach, volumetric absorptive micro-sampling (VAMS), in the context
      of the determination of ultra-trace concentrations of prosthesis-related metals
      (Al, Ti, V, Co, Cr, Ni, Sr and Zr) in whole blood. In a first phase, a simple
      dilute-and-shoot approach (100-fold dilution) followed by tandem ICP - mass
      spectrometry (ICP-MS/MS) analysis was developed for the accurate and sensitive
      determination of the target elements. The ICP-MS/MS method relies on the use of
      mass shift reactions proceeding when pressurizing the collision/reaction cell
      (CRC) with CH3F/He for dealing with spectral overlap. Limits of detection (LoDs)
      between 0.3 and 30 ng L-1 were attained in a multi-element approach. The accuracy
      of the method was demonstrated via successful analysis of the reference materials
      Seronorm Whole Blood Levels 1 and 3, and real venous blood samples, spiked with
      the target elements at different concentration levels (5-50 MUg L-1). Although
      the implementation of VAMS devices introduced contamination problems for Al, Cr
      and Ni, VAMS followed by ICP-MS/MS analysis shows potential for future real-life
      routine applications when assessing levels of Ti, V, Co, Sr and/or Zr.

PMID- 27692373
TI  - A review of the determination of persistent organic pollutants for environmental
      forensics investigations.
AB  - The field of environmental forensics emerged in the 1980s as a consequence of
      legislative frameworks enacted to enable parties, either states or individuals,
      to seek compensation with regard to contamination or injury due to damage to the
      environment. This legal environment requires stringent record keeping and
      defendable data therefore analysis can sometimes be confined to data to be
      obtained from certified laboratories using a standard accredited analytical
      method. Many of these methods were developed to target specific compounds for
      risk assessment purposes and not for environmental forensics applications such as
      source identification or age dating which often require larger data sets. The
      determination of persistent organic pollutants (POPs) for environmental forensic
      applications requires methods that are selective but also cover a wide range of
      target analytes which can be identified and quantified without bias. POPs are
      used in a wide variety of applications such as flame retardants, fire
      suppressants, heat transfer agents, surfactants and pesticides mainly because of
      their chemical inertness and stability. They also include compounds such as
      dioxins that can be unintentionally produced from industrial activities. POPs are
      persistent in the environment, bioaccumulative and/or toxic and therefore require
      analytical methods that are sensitive enough to meet the low detection limits
      needed for the protection of the environment and human health. A variety of
      techniques, procedures and instruments can be used which are well suited for
      different scenarios. Optimised methods are important to ensure that analytes are
      quantitatively extracted, matrix coextractables and interferences are removed and
      instruments are used most effectively and efficiently. This can require deviation
      from standard methods which can open the data up to further scrutiny in the
      courtroom. However, when argued effectively and strict QA/QC procedures are
      followed the development and optimization of methods based on investigation
      specific scenarios has the potential to generate better quality and more useful
      data.

PMID- 27692374
TI  - Continuous and real-time bioaerosol monitoring by combined aerosol-to-hydrosol
      sampling and ATP bioluminescence assay.
AB  - We present a methodology for continuous and real-time bioaerosol monitoring
      wherein an aerosol-to-hydrosol sampler is integrated with a bioluminescence
      detector. Laboratory test was conducted by supplying an air flow with entrained
      test bacteria (Staphylococcus epidermidis) to the inlet of the sampler. High
      voltage was applied between the discharge electrode and the ground electrode of
      the sampler to generate air ions by corona discharge. The bacterial aerosols were
      charged by the air ions and sampled in a flowing liquid containing both a cell
      lysis buffer and adenosine triphosphate (ATP) bioluminescence reagents. While the
      liquid was delivered to the bioluminescence detector, sampled bacteria were
      dissolved by the cell lysis buffer and ATP was extracted. The ATP was reacted
      with the ATP bioluminescence reagents, causing light to be emitted. When the
      concentration of bacteria in the aerosols was varied, the ATP bioluminescence
      signal in relative light units (RLUs) closely tracked the concentration in
      particles per unit air volume (# cm-3), as measured by an aerosol particle sizer.
      The total response time required for aerosol sampling and ATP bioluminescence
      detection increased from 30 s to 2 min for decreasing liquid sampling flow rate
      from 800 to 200 MULPM, respectively. However, lower concentration of S.
      epidermidis aerosols was able to be detected with lower liquid sampling flow rate
      (1 RLU corresponded to 6.5 # cm-3 of S. epidermidis aerosols at 200 MULPM and
      25.5 # cm-3 at 800 MULPM). After obtaining all data sets of concentration of S.
      epidermidis aerosols and concentration of S. epidermidis particles collected in
      the flowing liquid, it was found that with our bioluminescence detector, 1 RLU
      corresponded to 1.8 * 105 (+/-0.2 * 105) # mL-1 of S. epidermidis in liquid.
      After the lab-test with S. epidermidis, our bioaerosol monitoring device was
      located in the lobby of a building. Air sampling was conducted continuously for
      90 min (air flow rate of 8 LPM, liquid flow rate of 200 MULPM) and the ATP
      bioluminescence signal of indoor bioaerosols was displayed with time. Air
      sampling was also carried out using the 6th stage of Andersen impactor in which a
      nutrient agar plate was used for the impaction plate. The sample was cultured at
      37  degrees C for five days for colony counting. As a result, it was found that
      the variation of the bioluminescence signal closely followed the variation of
      indoor bioaerosol concentration in colony forming unit (CFU) and 1 RLU
      corresponded to 1.66 CFU m-3 of indoor bioaerosols. Our method can be used as a
      trigger in biological air contamination alarm systems.

PMID- 27692375
TI  - Development and validation of an at-line fast and non-destructive Raman
      spectroscopic method for the quantification of multiple components in liquid
      detergent compositions.
AB  - Implementation of process analytical technology (PAT) tools in the manufacturing
      process of liquid detergent compositions should allow fast and non-destructive
      evaluation of the product quality. The aim of this study was to develop and
      validate a rapid method for quantifying the chemical compounds of five washing
      liquid precursors. Raman spectroscopy was applied in combination with a two-step
      multivariate modeling procedure. In first instance, a SIMCA (Soft Independent
      Modeling of Class Analogy) model was developed and validated, allowing the
      distinction between the different laundry detergents. Once the product was
      correctly identified, it was aimed at predicting the concentration of its
      individual components using partial least squares (PLS) models. Raman spectra
      were collected at-line with a total acquisition time of 20 s, using a non-contact
      fiber-optic probe. The SIMCA model was perfectly capable of differentiating
      between the classes of the laundry liquid precursors. Per detergent, the
      concentration of at least three main ingredients could be predicted with a
      recovery between 98% and 102% and a standard deviation below 2.5%. Accuracy
      profiles based on the analysis results of validation samples were then calculated
      to prove the reliability of the developed regression models. beta-expectation
      tolerance intervals were calculated for each model and for each validated
      concentration level. The acceptance limits were set at 5% relative bias,
      indicating that at least 95% of future measurements should not deviate more than
      5% from the true value. Furthermore, based on the data of the accuracy profiles,
      the measurement uncertainty was determined. The developed Raman spectroscopic
      method demonstrated to be able to rapidly and adequately determine the
      concentration of the components of interest in the liquid detergent compositions
      at-line.

PMID- 27692376
TI  - Nickel electrodes as a cheap and versatile platform for studying structure and
      function of immobilized redox proteins.
AB  - Practical use of many bioelectronic and bioanalytical devices is limited by the
      need of expensive materials and time consuming fabrication. Here we demonstrate
      the use of nickel electrodes as a simple and cheap solid support material for
      bioelectronic applications. The naturally nanostructured electrodes showed a
      surprisingly high electromagnetic surface enhancement upon light illumination
      such that immobilization and electron transfer reactions of the model redox
      proteins cytochrome b5 (Cyt b5) and cytochrome c (Cyt c) could be followed via
      surface enhanced resonance Raman spectroscopy. It could be shown that the nickel
      surface, when used as received, promotes a very efficient binding of the proteins
      upon preservation of their native structure. The immobilized redox proteins could
      efficiently exchange electrons with the electrode and could even act as an
      electron relay between the electrode and solubilized myoglobin. Our results open
      up new possibility for nickel electrodes as an exceptional good support for
      bioelectronic devices and biosensors on the one hand and for surface enhanced
      spectroscopic investigations on the other hand.

PMID- 27692377
TI  - ICE Concentration Linked with Extractive Stirrer (ICECLES).
AB  - Trace and ultra-trace analysis can be difficult to achieve, especially for polar,
      more volatile, and/or thermally unstable analytes. A novel technique, coined ICE
      Concentration Linked with Extractive Stirrer (ICECLES), may help address this
      problem. The implementation of ICECLES described here combines stir bar sorptive
      extraction (SBSE) with freeze concentration (FC), where an aqueous solution is
      frozen during SBSE in order to concentrate analytes into a polydimethylsiloxane
      (PDMS) coated stir bar. Five test probe molecules with a range of log Kows (2
      butanol, benzyl alcohol, benzaldehyde, dimethyl trisulfide and bromobenzene) were
      prepared from aqueous solutions using ICECLES. Thermal desorption gas
      chromatography mass-spectrometry was then used to quantify these analytes.
      Parameters affecting the performance of ICECLES (e.g., freeze rate) were
      evaluated, with extraction at lower speeds resulting in higher extraction
      efficiencies, whereas the freeze rate and initial analyte concentration only had
      a minor effect. ICECLES produced much higher extraction efficiencies than SBSE
      alone, with signal enhancements of up to 474* SBSE. ICECLES also provided
      excellent reproducibility and lower LODs than SBSE for all compounds tested.
      ICECLES performed well when used to analyze multiple triazine pesticides and
      breakdown products in environmental surface waters. Overall, the ICECLES
      technique was excellent at preparing aqueous samples for trace analysis and shows
      promise as a novel analytical sample preparation technology.

PMID- 27692378
TI  - Automated peak width measurements for targeted analysis of ion mobility
      unresolved species.
AB  - Peak broadening in ion mobility (IM) is a relatively predictable process and
      abnormally broad peaks can be indicative of the presence of unresolved species.
      Here, we introduce a new ion mobility peak fitting (IM_FIT) software package for
      automated and systematic determination of traveling wave ion mobility (TWIM)
      unresolved species. To identify IM unresolved species, the IM_FIT software
      generates a trend line by plotting ions' mobility peak widths as a function of
      their arrival times. Utilizing user-defined thresholds, IM_FIT allows for
      automated and rapid detection of ions that deviate from the peak width trend
      line. To demonstrate the advantages of IM_FIT for automated detection of IM
      unresolved species, IM-mass spectrometry (IM-MS) data from a sample mixture
      containing polypropylene glycol and multiple peptides were analyzed. A total of
      14 out of the 34 observed singly-charged IM peaks above 5% relative abundance
      (i.e., signal-to-noise ratios above ~200) were tagged as potentially co-eluting
      ions by IM_FIT. Subsequently, the 14 IM peaks tagged as potentially unresolved
      (presumably, peaks corresponding to co-eluting compounds), were further analyzed
      by automated IM deconvolution (AIMD), liquid chromatography-IM-MS (LC-IM-MS),
      and/or ultra-high resolution mass spectrometry. Using the aforementioned
      techniques, more than 85% of the tagged IM peaks (12 out of 14) were confirmed to
      contain co-eluting ions. As an additional new finding, IM_FIT facilitated the
      discovery of an unexpected sequence-scrambled y-type fragment ion.

PMID- 27692379
TI  - Measuring urinary N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (IPMA3)
      as a potential biomarker of isoprene exposure.
AB  - Isoprene, the 2-methyl analog of 1,3-butadiene, is identified as a possible human
      carcinogen by the International Agency for Research on Cancer (IARC). Isoprene is
      ubiquitous in the environment with numerous natural and anthropogenic sources.
      Tobacco smoke is the main exogenous source of isoprene exposure in indoor
      environments. Among smoke constituents, isoprene is thought to contribute
      significantly to cancer risk; however, no selective urinary biomarkers of
      isoprene exposure have been identified for humans. In this manuscript, we
      measured the minor isoprene metabolite IPMA1 (mixture of N-acetyl-S-(1
      [hydroxymethyl]-2-methyl-2-propen-1-yl)-L-cysteine and N-acetyl-S-(2-hydroxy-3
      methyl-3-buten-1-yl)-L-cysteine), and we identified IPMA3 (N-acetyl-S-(4-hydroxy
      2-methyl-2-buten-1-yl)-L-cysteine) as a major isoprene metabolite and novel
      isoprene exposure biomarker for humans. Urinary isoprene metabolites were
      measured using ultra high performance liquid chromatography coupled with
      electrospray ionization triple quad tandem mass spectrometry (UPLC/ESI-MSMS). The
      detection rates of IPMA1 and IPMA3 are <20% and 82%, respectively. The
      selectivity and abundance of IPMA3 make it a useful urinary biomarker of isoprene
      exposure. The limit of detection of IPMA3 in urine was 0.5 ng mL-1. IPMA3 was
      stable under different storage temperatures and following ten freeze-thaw cycles.
      The average recovery of urine spiked with IPMA3 at three different levels was
      99%. IPMA3 was measured in urine samples received from 75 anonymous subjects; the
      median (25th percentile, 75th percentile) IPMA3 level in smokers was 36.2 (18.2,
      56.8) ng mL-1 and non-smokers 2.31 (2.31, 4.38) ng mL-1. Application of this
      method to large population studies will help to characterize isoprene exposure
      and assess potential health impact.

PMID- 27692380
TI  - Analyses of trace amounts of dyes with a new enhanced sensitivity FTIR
      spectroscopic technique: MU-ATR (metal underlayer ATR spectroscopy).
AB  - The identification of organic dyes is a challenging task in all the fields such
      as the forensic and conservation sciences, especially in cases where the amount
      of sample is extremely small. In this paper we propose a new enhanced FTIR method
      (MU-ATR metal underlayer ATR spectroscopy), which we believe is the first of its
      kind, for the analysis of a few ng of dyes. With this method, dyed fiber micro
      extracts can be analyzed using a commercial FTIR microscope with a fixed incident
      angle, obtaining the same separation between the different classes of dyes
      investigated as we obtained analyzing pure dyes in transmission mode. Moreover,
      the new enhancement method has been validated on a real sample dated back to the
      1893, showing how it can be promising for the analysis of trace amounts of
      organic substances in artistic samples such as dyes in paintings or textiles,
      varnishes and organic residues on archaeological objects.

PMID- 27692381
TI  - Protein determination using graphene oxide-aptamer modified gold nanoparticles in
      combination with Tween 80.
AB  - Recently, graphene oxide (GO) has shown superiority for disease detection arising
      from its unique physical and chemical properties. However, proteins adsorbed on
      the surface of GO prevent sensitivity improvement in fluorescence-based detection
      methods. In this paper, a label-free method based on aptamer modified gold
      nanoparticles (GNPs) combined with Tween 80 was shown to solve this problem using
      the detection of thrombin as an example. An aptamer was designed and bound to
      thrombin by changing its conformation. Tween 80 was used for rapid and
      reproducible synthesis of stable DNA-functionalized GNPs and prevented the
      thrombin from nonspecific binding to GO. Thrombin was detected with a limit of
      0.68 pM by taking advantage of the efficient cross-linking effect of aptamer-GNPs
      to GO. The sensor was validated by determining thrombin concentration in human
      blood serum samples. The results indicate that this method has promising
      analytical application in medical diagnostic.

PMID- 27692382
TI  - Peroxidase-like catalytic activity of copper ions and its application for highly
      sensitive detection of glypican-3.
AB  - Glypican-3 (GPC3) might be used as new biomarker of liver cancer for the
      development of new diagnostic methods. The most commonly used methods for protein
      detection are based on natural enzymes, which are easily affected by
      environmental conditions and suffer from the rigorous preparation conditions.
      Thus, the development of new enzyme mimetics with high and stable catalytic
      activity is of great significance in diagnostic applications. In this paper,
      copper ions (Cu2+) was found to possess the peroxidase-like catalytic activity,
      which can catalyze H2O2-mediated oxidation of peroxidase substrate and obtain the
      oxidation product with color change. This catalytic activity is much more stable
      than other nanomaterials based peroxidase mimetics, and can significantly
      increase by increasing the concentration of H2O2. It is worth mentioning that the
      absorbance signal induced by 5 nM Cu2+ can be easily detected. This Cu2+
      catalyzed reaction can be also applied in the detection of GPC3 by using the anti
      GPC3 antibody functionalized CuO NPs, which can release the Cu2+ by dissolved in
      HCl solution. This method permits detection of as low as 0.26 pg mL-1 GPC3. This
      sensitivity is about one or several magnitudes higher than that of ELISA or other
      peroxidase mimetics based methods. The high catalytic activity of Cu2+ and the
      signal amplification process of CuO NPs into high amount of Cu2+ also make this
      method more simple and effective.

PMID- 27692383
TI  - Application of DNA aptamers as sensing layers for detection of carbofuran by
      electrogenerated chemiluminescence energy transfer.
AB  - In this study, an electrogenerated chemiluminescence (ECL) sensing platform for
      carbofuran detection was constructed based on ECL energy transfer (ECRET) and
      carbon dot (C-dot)-tagged aptamers as the recognition element. Fullerene (C60)
      loaded gold nanoparticles (C60-Au) were used as the energy donor, modified on a
      glassy carbon electrode. C-dot-tagged DNA aptamers were used as the receptor, and
      ECRET then occurred between C60-Au and C-dots. After accepting the energy, the C
      dots acted as a signal indicator and showed decreased signal intensity in the
      presence of targets, which competitively bound to DNA aptamers and blocked energy
      transfer. Using this robust, straight-forward strategy, the sensor showed a
      linear ECL response to carbofuran at concentrations from 2.0 * 10-11 mol L-1 to
      8.0 * 10-9 mol L-1. The detection limit of this assay was shown to be 8.8 * 10-13
      mol L-1. Thus, the sensing approach described in this study could be adapted for
      use in the detection of various pesticide residue targets.

PMID- 27692385
TI  - Obesity in Asia and Oceania - Lifespan, health and genes.

PMID- 27692384
TI  - [Compliance and leaflet's reading, which link and which media? Results from a
      French population with chronic kidney disease].
AB  - Leaflets inside drug boxes are complex and often poorly understood. Patients
      consulting in nephrology are mostly old and often suffer from multiple
      comorbidities. As so, they are often subject to various contra-indications and
      drug interactions. This paper aims to evaluate if patients actually read leaflets
      or other medical information on others medias such as Internet and whether this
      could, potentially, interfere with their observance. Results showed that leaflets
      were read by 65.1% of patients, leading to 12% of withdrawal or not taking drugs.
      Furthermore, compliance to medical guidance was deemed e-read by 65.1% of
      patients, leading to 12% of withdrawal or not taken drugs. Furthermore, this
      study showed no clear profile for non-compliant patients. Even the youngest
      patients (under 50 years old) have had a good compliance, with not more
      withdrawal or not taking pills. Nonetheless, youngest patients used more often to
      consult alternative medias and did not read much of the leaflets' information.
      Patients who were reading leaflets however, tended to search further information
      on other medias. This situation would create new challenges in health care, as it
      seems that data available on new medias are not systematically validated or
      adapted to the needs of the patients.

PMID- 27692386
TI  - The European Portuguese adaptation of the Fear of Pain Questionnaire.
AB  - In Portugal, it is estimated that chronic pain affects 36.7% of the population,
      constituting a multifactorial phenomenon with great impact at individual, family,
      community, and social levels. In the fear-avoidance model of pain, one of the
      most consistent consensual in the literature, the fear arises as one of the
      variables that can contribute to the development and maintenance of this
      condition. Thus, instruments for evaluating the fear of pain, as Fear of Pain
      Questionnaire (FPQ-III), may be useful in the conceptualization of the subjective
      experience of pain. Accordingly, this paper aims to describe the adaptation of
      FPQ-III for the European Portuguese. A total of 1094 participants (795 women;
      mean age=25.16, SD=7.72) completed the web based questionnaire. The results
      pointed to a different factor solution found in the first study of the original
      scale (five factors: minor pain, severe pain, medical pain, injection pain, and
      afflicted pain), good internal consistency (.75-.85) and good correlations
      (between .30 and .59) between subscales and (between .68 and .85) for the total
      score and subscales. Given the need to meet the various dimensions of subjective
      experience of pain, the Fear of Pain Questionnaire is assumed as a useful tool,
      in combination with other, may contribute to the evaluation and intervention
      procedures progressively more comprehensive and adjusted to the challenges raised
      with the issue of chronic pain.

PMID- 27692387
TI  - A prospective study predicting the outcome of chronic low back pain and physical
      therapy: the role of fear-avoidance beliefs and extraspinal pain.
AB  - OBJECTIVE: To identify the prognostic factors for conventional physical therapy
      in patients with chronic low back pain (CLBP). METHODS: Prospective observational
      study. PARTICIPANTS: One hundred thirteen patients with CLBP selected at the
      Spinal Disease Outpatient Clinic. MAIN OUTCOME MEASURES: Pain intensity was
      scored using the Numeric Rating Scale (NRS), and function was measured using the
      Roland-Morris Disability Questionnaire (RMDQ). RESULTS: The Fear-Avoidance
      Beliefs Questionnaire work subscale results (FABQ-work; odds ratio [OR]=0.27, 95%
      confidence interval [CI] 0.13-0.56, p<0.001) and extraspinal pain (OR=0.35, 95%
      CI 0.17-0.74, p=0.006) were independently associated with a decreased response to
      conventional physical therapy for CLBP. CONCLUSION: We identified high FABQ-work
      and extraspinal pain scores as key determinants of a worse response to physical
      therapy among CLBP patients, supporting the need for a special rehabilitation
      program for this subgroup.

PMID- 27692388
TI  - High frequency of asymptomatic hyperparathyroidism in patients with fibromyalgia:
      random association or misdiagnosis?
AB  - : Fibromyalgia (FM) and hyperparathyroidism may present similar symptoms
      (musculoskeletal pain, cognitive disorders, insomnia, depression and anxiety),
      causing diagnostic confusion. OBJECTIVES: To determine the frequency of
      asymptomatic hyperparathyroidism in a sample of patients with FM and to evaluate
      the association of laboratory abnormalities to clinical symptoms. METHODS: Cross
      sectional study with 100 women with FM and 57 healthy women (comparison group).
      Parathyroid hormone (PTH), calcium and albumin levels were accessed, as well as
      symptoms in the FM group. RESULTS: In FM group, mean serum calcium (9.6+/
      0.98mg/dL) and PTH (57.06+/-68.98pg/mL) values were considered normal, although
      PTH levels had been significantly higher than in the comparison group (37.12+/
      19.02pg/mL; p=0.001). Hypercalcemic hyperparathyroidism was diagnosed in 6% of
      patients with FM, and 17% of these women exhibited only high levels of PTH,
      featuring a normocalcemic hyperparathyroidism, with higher frequencies than those
      expected for their age. There was no significant association between
      hyperparathyroidism and FM symptoms, except for epigastric pain, which was more
      frequent in the group of patients concomitantly with both diseases (p=0.012).
      CONCLUSIONS: A high frequency of hyperparathyroidism was noted in women with FM
      versus the general population. Normocalcemic hyperparathyroidism was also more
      frequent in patients with FM. Longitudinal studies with greater number of
      patients are needed to assess whether this is an association by chance only, if
      the increased serum levels of PTH are part of FM pathophysiology, or even if
      these would not be cases of FM, but of hyperparathyroidism.

PMID- 27692389
TI  - The representation of getting ill in adolescents with systemic lupus
      erythematosus.
AB  - INTRODUCTION: This study, developed in a federal hospital in the city of Rio de
      Janeiro, has aimed to analyze the social representation of chronic disease and
      its treatment, in the perspective of adolescents and their caregivers. METHODS:
      The sample consisted of 31 adolescents (11-21 years) with systemic lupus
      erythematosus and 19 caregivers (32-66 years), followed in the pediatrics and in
      the internal medicine outpatient clinics for a period of six months. Data was
      collected from the free association of words test, using chronic disease and
      treatment of chronic disease impulses, and later submitted to the Multiple
      Correspondence Analysis using the R software. RESULTS: The group of adolescents
      associated the impulse chronic disease with the words medication, bad, illness,
      difficulty, no cure, faith and joy; and in the group of caregivers, to care,
      treatment, no cure and the word 'no'. The impulse treatment of chronic disease
      was associated, in the group of adolescents, with the words patience,
      improvement, help, affection, care and bad; and in the group of caregivers, to
      caring, hope, schedule, knowledge, obedience, medication, professional and
      improvement. Caregivers also associated impulses and words according to age:
      chronic disease was associated with the word care (over 61 years), pain and
      impotence (42-61 years), treatment (22-41 years); and treatment of chronic
      disease, with the words strength (over 61 years), professional, knowledge and
      improvement (42-61 years), affection and schedule (22-41 years). CONCLUSIONS:
      Considering as subjective and dynamic the experience of getting ill, knowing the
      representations can contribute to the orientation of conduct and type of
      psychotherapeutic intervention needed.

PMID- 27692390
TI  - Sensitivity and specificity of assessment instruments of quality of life in
      rheumatoid arthritis.
AB  - OBJECTIVE: To check sensitivity and specificity of assessment instruments of QoL
      in patients with rheumatoid arthritis (RA). METHODOLOGY: Accuracy study in a
      sample consisting of patients with confirmed diagnosis of RA. QoL questionnaires
      QV SF-36 (Gold Standard), HAQ and NHP were applied. The Pearson correlation
      coefficient, ROC curve, AUC and Youden Index (J) were used to analyze the data.
      RESULTS: This study enrolled 97 individuals with RA. The functional capacity
      estimated by SF-36 was correlated with the total score of HAQ (r=-0.666; p<0.001;
      J=0.579), while the emotional aspects of SF-36 were correlated with the emotional
      reactions domain of NHP (r=-0.316; p=0.005; J=0.341). The vitality domain of SF
      36 was correlated with the level of energy of NHP (r=-0.362; p=0.001; J=0.302).
      For the evaluation of functional capacity (AUC=0.839; p<0.001) and physical
      aspect (AUC=0.755; p<0.001) the most accurate instrument was the HAQ. For
      evaluation of the impact of vitality, sleep (AUC=0.679; p=0.007), emotional
      reactions (AUC=0.674; p=0.009) and level of energy in QoL, the NHP (AUC=0.633;
      p=0.045) was the most specific and sensitive. In the evaluation of the emotional
      aspect domain, the most accurate instrument was the NHP in the "emotional
      reaction" score (AUC=0.699; p=0.003). The evaluation of pain was limited in the
      three instruments and SF-36 was the only one in assess of the domains of social
      aspects and general health status. CONCLUSION: For evaluation of the physical
      aspects in patients with RA, the HAQ is the most accurate. For evaluation of
      emotional aspects the NHP is the most indicated, although the SF-36 was the only
      one in the evaluation of general domains.

PMID- 27692391
TI  - Methylene tetrahydrofolate reductase, transforming growth factor-beta1 and
      lymphotoxin-alpha genes polymorphisms and susceptibility to rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis is a widely prevalent autoimmune disorder with
      suggested genetic predisposition. OBJECTIVES: The aim of this study is to detect
      the pattern of genetic polymorphism of methylene tetrahydrofolate reductase
      (MTHFR C677 T and A1298 C), transforming growth factor-beta1 (TGF-beta1 T869 C)
      and lymphotoxin-alpha (LT-alpha A252G) in patients having rheumatoid arthritis
      and correlate these patterns to disease activity and serum levels of tumor
      necrosis factor-alpha (TNF-alpha), B-Cell Activating Factor (BAFF), and
      osteopontin. METHODS: A total of 194 subjects, 90 controls and 104 patients with
      rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-beta1 T869
      C and LT-alpha A252G polymorphisms using a methodology based on PCR-RFLP. Also
      serum levels of TNF-alpha, osteopontin and BAFF were measured by ELISA kits.
      RESULTS: The CT genotype and T allele of MTHFR C677 T and GG genotype and G
      allele of LT-alpha A252G are associated with the risk of RA and with higher
      levels of the pro-inflammatory cytokine, TNF-alpha in patients with rheumatoid
      arthritis. CONCLUSION: Our findings suggest that there is association between
      MTHFR C677 T and LT-alpha A252G genes polymorphisms and increased risk of RA in
      this sample of Egyptian population.

PMID- 27692392
TI  - A new musculoskeletal ultrasound scoring system (US10) of the hands and wrist
      joints for evaluation of early rheumatoid arthritis patients.
AB  - OBJECTIVE: To propose a novel ultrasound scoring system for hand and wrist joints
      (US10) for evaluation of patients with early rheumatoid arthritis (RA) and to
      correlate the US10 with clinical, laboratory and functional variables. METHODS:
      Forty-eight early RA patients underwent clinical and laboratory evaluations as
      well as blinded ultrasound (US) examinations at baseline, three, six and 12
      months. The proposed US10 system involved the assessment of the wrist, second and
      third metacarpophalangeal and proximal interphalangeal joints. The score
      consisted of inflammation parameters (synovial proliferation [SP], power Doppler
      [PD] and tenosynovitis [TN]) and joint damage parameters (bone erosion [BE] and
      cartilage damage [CD]). SP, PD, BE and CD were scored qualitatively (0-1) and
      semi-quantitatively (grades 0-3). Tenosynovitis was scored as presence/absence.
      The evaluation also involved the 28-Joint Disease Activity Score (DAS28), Health
      Assessment Questionnaire (HAQ) and C-reactive protein level (CRP). RESULTS: Mean
      duration of symptoms was 7.58+/-3.59 months. Significant correlations (p<0.05)
      were found between inflammation parameters and CRP at baseline and between the
      changes in these variables throughout the study. Significant correlations
      (p<0.05) were found between DAS28 score and both PD and TN at baseline and
      between the changes in DAS28 score and both SP and TN throughout the follow up.
      Moreover, significant correlations were found between the changes in inflammation
      parameter scores and HAQ score throughout the follow up. CONCLUSION: The proposed
      US10 scoring system proved to be a useful tool for monitoring inflammation and
      joint damage in early RA patients, demonstrating significant correlations with
      longitudinal changes in disease activity and functional status.

PMID- 27692393
TI  - Clinical characteristics and frequency of TLR4 polymorphisms in Brazilian
      patients with ankylosing spondylitis.
AB  - OBJECTIVES: Innate immunity is involved in the physiopathology of ankylosing
      spondylitis (AS), with the participation of Gram-negative bacteria, modulation of
      human leukocyte antigen (HLA) B27 and the involvement of pattern recognition
      receptors, such as Toll-like receptors (TLRs). The aim of this study was to
      investigate the clinical characteristics and frequency of TLR4 polymorphisms
      (Asp299Gly and Thr 399Ile) in a cohort of Brazilian patients with AS. METHODS: A
      cross-sectional study was carried out involving 200 patients with a diagnosis of
      AS and a healthy control group of 200 individuals. Disease activity, severity and
      functional capacity were measured. The study of TLR4 polymorphisms was performed
      using the restriction fragment length polymorphism method. HLA-B27 was analyzed
      by conventional polymerase chain reaction. The IBM SPSS Statistics 20 program was
      used for the statistical analysis, with p-values less than 0.05 considered
      significant. RESULTS: Mean age and disease duration were 43.1+/-12.7 and 16.6+/
      9.2 years, respectively. The sample was predominantly male (71%) and non
      Caucasian (52%). A total of 66% of the group of patients were positive for HLA
      B27. The sample of patients was characterized by moderate functional impairment
      and a high degree of disease activity. No significant association was found
      between the two TLR4 polymorphisms and susceptibility to AS. CONCLUSIONS: TLR4
      polymorphisms 399 and 299 were not more frequent in patients with AS in
      comparison to the health controls and none of the clinical variables were
      associated with these polymorphisms.

PMID- 27692394
TI  - What rheumatologists should know about orofacial manifestations of autoimmune
      rheumatic diseases.
AB  - Orofacial manifestations occur frequently in rheumatic diseases and usually
      represent early signs of disease or of its activity that are still neglected in
      clinical practice. Among the autoimmune rheumatic diseases with potential for
      oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM),
      systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing
      polychondritis (RP) and Sjogren's syndrome (SS) can be cited. Signs and symptoms
      such as oral hyposalivation, xerostomia, temporomandibular joint disorders,
      lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be
      the first expression of these rheumatic diseases. This article reviews the main
      orofacial manifestations of rheumatic diseases that may be of interest to the
      rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases.

PMID- 27692395
TI  - IL33 in rheumatoid arthritis: potential contribution to pathogenesis.
AB  - A better understanding of the inflammatory mechanisms of rheumatoid arthritis and
      the development of biological therapy revolutionized its treatment, enabling an
      interference in the synovitis - structural damage - functional disability cycle.
      Interleukin 33 was recently described as a new member of the interleukin-1
      family, whose common feature is its pro-inflammatory activity. Its involvement in
      the pathogenesis of a variety of diseases, including autoimmune diseases, raises
      the interest in the possible relationship with rheumatoid arthritis. Its action
      has been evaluated in experimental models of arthritis as well as in serum,
      synovial fluid and membrane of patients with rheumatoid arthritis. It has been
      shown that the administration of interleukin-33 exacerbates collagen-induced
      arthritis in experimental models, and a positive correlation between cytokine
      concentrations in serum and synovial fluid of patients with rheumatoid arthritis
      and disease activity was found. This review discusses evidence for the role of
      interleukin-33 with a focus on rheumatoid arthritis.

PMID- 27692396
TI  - Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single
      center.
AB  - : Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity
      and mortality. Although cyclophosphamide is effective for severe and refractory
      cases, there is demand for new treatments. The biological treatment with B-cell
      depletion with rituximab (RTX) has demonstrated efficacy for this demand in open
      label studies. OBJECTIVE: This study was conducted with the aim to
      retrospectively evaluate all patients who used RTX for the treatment of SSc in
      our center. PATIENTS AND METHODS: We retrospectively evaluated medical records of
      all patients with SSc who used RTX to treat this disease from January 2009 to
      January 2015. Systemic, cutaneous, and pulmonary involvement data and laboratory
      results before and six months after the first infusion of RTX were collected.
      RESULTS: Ten patients received treatment during the study period and were
      included in this series. All patients had a diffuse form of the disease. Five
      patients suffered from an early (duration of disease shorter or equal to four
      years), rapidly progressive disease, and another five received RTX at late stages
      of the disease. In both groups of patients, stabilization of the pulmonary
      picture was observed, with a fall in the skin score in those patients with early
      forms of the disease. DISCUSSION: Similar to findings in previous studies, RTX
      was effective in treating early and rapidly progressive forms of SSc. We also
      found that patients with long-term illness may benefit from the treatment.

PMID- 27692397
TI  - Did Father Cicero suffer from rheumatism?
AB  - Father Cicero Romao Batista is probably the most famous Ceara character of all
      time. An important protagonist of the Cariri region, situated in the south of
      Ceara State, in the late nineteenth century and the first third of the twentieth
      century, Father Cicero had great political and religious activity, as well as
      other less well-known achievements, for instance, his ecological teachings that
      led him to be awarded the title of "Patron of Forests", besides an enormous
      effort and personal sacrifice for the improvement of the conditions of human
      life. Inspired by reading his biography, we find that the "Padim Cico" could have
      inflammatory spondyloarthropathy. In this article, we present the plausibility of
      this diagnostic hypothesis, seeking to emphasize that an attentive ear and
      clinical observation, albeit indirectly and without the privilege of a personal
      contact with the patient, are unparalleled tools for bringing forth a diagnosis.

PMID- 27692399
TI  - Acetylcholine-induced ex vivo ATP release from the human nasal mucosa.
AB  - OBJECTIVE: The present study aimed at investigating ATP release in response to
      acetylcholine (Ach) and pharmacologically elucidating the intracellular signal
      transduction pathway of this reaction in an ex vivo experiment. METHODS: The
      inferior turbinate mucosa was collected from 21 patients with chronic
      hypertrophic rhinitis who underwent endoscopic turbinectomy. The mucosa was
      shaped into a filmy round piece, and incubated with chemical(s) in Hank's
      balanced salt solution for 10min. After incubation, the ATP concentration was
      measured by a luciferin-luciferase assay. RESULTS: The baseline release of ATP
      without stimulus was 57.2+/-10.3fM. The ATP release was significantly increased
      by stimulation with 100MUM Ach. The Ach-induced ATP release was completely
      inhibited by removing extracellular Ca2+. Significant inhibition of the Ach
      induced ATP release was also observed by the addition of 1MUM atropine, 40MUM 2
      APB, 10MUM CBX, and 100MUM PPADS, whereas 30nM bafilomycin A1 did not affect the
      ATP release. CONCLUSION: These results indicate that the Ach-induced ATP release
      from the human nasal mucosa is dependent on the pannexin-1 channel and purinergic
      P2X7 receptor, suggesting that these two molecules constitute a local
      autocrine/paracrine signaling system in the human nasal epithelium.

PMID- 27692398
TI  - New approach in lung cancer radiotherapy offers better normal tissue sparing.
AB  - PURPOSE: Medical images are more than pictures. They contain additional
      quantitative information which can be interrogated, quantified, and utilized.
      Besides anatomical information computed tomography (CT) imaging data provide
      electron density information. Radiotherapy use of this density information is
      limited to its application only in dose calculations. The direct product of dose,
      density, and volume forms a quantity called integral dose. The integral dose
      delivered to a volume of interest is the total energy deposited in that volume.
      Here it is hypothesized that minimization of the integral dose is advantageous in
      radiotherapy planning. The purpose of this work is to study the incorporation of
      quantitative imaging information in radiotherapy inverse optimization through
      total energy minimization (Energy hereafter). DESIGN: Twenty lung patient plans
      were studied. For each patient density was quantified on voxel-by-voxel basis
      through image gray value-to-density conversion curves. Energy-based objective
      function was used for inverse radiotherapy plan optimization. The obtained plans
      were evaluated in the light of current standard of care, based on dose-volume
      (DVH) optimization approach. RESULTS: The statistical significance analyses of
      the results indicated that the doses to normal tissue were between 14% and 45%
      lower, when Energy-based optimization was used instead of DVH-based optimization.
      CONCLUSION: Incorporation of quantitative imaging information, through CT derived
      density, in the optimization cost function allows reduction of dose to normal
      tissue for NSCLC cases. Energy-based radiotherapy plans result in lower normal
      tissue dose and potentially lower complication rates compared to standard of
      care.

PMID- 27692400
TI  - The role of nasal fractional exhaled nitric oxide as an objective parameter
      independent of nasal airflow resistance in the diagnosis of allergic rhinitis.
AB  - OBJECTIVE: Patients with allergic rhinitis (AR) show augmented activity of nitric
      oxide (NO) metabolism, similar to those in bronchial asthma (BA). We hypothesized
      that measurements of nasal fractional exhaled NO (FeNO) could be used as an
      objective marker to detect the presence of AR. Our objective was to clarify the
      influence of nasal airflow resistance (NAR) on nasal FeNO levels through an
      exhalation maneuver in symptomatic AR patients. We also examined the diagnostic
      test validity of the mean nasal FeNO level for disease discrimination by means of
      a receiver operating characteristic (ROC) curve analysis. METHODS: Fifty-nine
      untreated perennial AR patients without BA and 60 healthy controls were enrolled
      in this retrospective cross-sectional study. The subjective symptoms were
      recorded and the disease severity was classified according to the Japanese
      guideline for AR. The oral and nasal FeNO measurements were carried out using a
      handheld electrochemical analyzer according to the ATS/ERS guidelines. NAR was
      measured using a rhinomanometer by the anterior method. RESULTS: The patients in
      the moderate-to-most severe AR group showed significantly higher levels of oral
      FeNO compared to the controls. The AR patients in both the mild (n=25) and the
      moderate-to-most severe (n=34) groups showed significantly higher levels of nasal
      FeNO compared to the controls (44.1ppb, 54.5ppb, and 26.5ppb, respectively).
      There was no significant difference in total NAR between the AR patients and the
      controls. The results of our comparison of nasal FeNO and NAR values of the
      ipsilateral nasal cavity for each individual indicated no significant correlation
      between the two-paired parameters. The optimal cut-off point of the mean nasal
      FeNO level was calculated as 38.5ppb (with 71% sensitivity and 86% specificity)
      to discriminate the presence of AR. CONCLUSION: Nasal FeNO measurements can be an
      objective parameter for the diagnosis and classification of perennial AR in
      Japanese individuals. Nasal FeNO and NAR appear to be two independent measures
      that can be used to objectively evaluate nasal functions.

PMID- 27692401
TI  - Type II topoisomerases: Experimental studies, theoretical models, and logic:
      Reply to comments on "Disentangling DNA molecules".

PMID- 27692402
TI  - Why are we fighting the Medical Device Excise Tax?

PMID- 27692403
TI  - Why we are fighting the Medical Device Excise Tax.

PMID- 27692404
TI  - Rapid canine retraction: Is it actually happening?

PMID- 27692405
TI  - Authors' response.

PMID- 27692406
TI  - Herbst appliance anchored to miniscrews with 2 types of ligation.

PMID- 27692407
TI  - Authors' response.

PMID- 27692408
TI  - Long-term stability of maxillary group distalization with interradicular
      miniscrews.

PMID- 27692409
TI  - Authors' response.

PMID- 27692410
TI  - Correction.

PMID- 27692412
TI  - Tell it like it is.

PMID- 27692414
TI  - Retrieval analysis of lingual fixed retainer adhesives.
AB  - INTRODUCTION: Our objective was to analyze the surface and bulk properties
      alterations of clinically aged composites used for fixed retention. METHODS:
      Twenty-six lingual retainers bonded for different time periods (2.2-17.4 years)
      were retrieved from postorthodontic patients. Fifteen lingual retainers had been
      cemented by a chemically cured adhesive (Maximum Cure, Reliance Orthodontic
      Products, Itasca, Ill), and 11 were treated with a photo-cured adhesive (Flow
      Tain, Reliance Orthodontic Products). The first group was in service for 2.8 to
      17.4 years and the second for 2.2 to 5.4 years. Five specimens from each material
      were prepared and used as the control (or reference) group. The debonded surfaces
      from enamel were studied by attenuated total reflectance Fourier transform
      infrared spectroscopy (n = 3 per material per group), low-vacuum scanning
      electron microscopy, and energy dispersive x-ray microanalysis (n = 3 per
      material per group). All specimens were used for the assessment of Vickers
      hardness, indentation modulus, and elastic index with the instrumented
      indentation testing method. The values of Vickers hardness, indentation modulus,
      and elastic index were compared between the retrieved and the reference groups
      with 1-way analysis of variance and the Student-Newman-Keuls multiple comparison
      test (alpha = 0.05). RESULTS: The attenuated total reflectance Fourier transform
      infrared spectroscopy analysis showed that both retrieved composites demonstrated
      reduced unsaturation in comparison with the corresponding reference specimens.
      Some bonded surfaces showed development of organic integuments. All retrieved
      specimens showed reduced silicon content. Barium was identified only in the photo
      cured group. No significant differences were found between the reference and
      retrieved groups in Vickers hardness, indentation modulus, and elastic index.
      CONCLUSIONS: Despite the changes in composition, the mechanical properties of the
      materials tested remained unaffected by intraoral aging.

PMID- 27692413
TI  - Dentoskeletal outcomes of a rapid maxillary expander with differential opening in
      patients with bilateral cleft lip and palate: A prospective clinical trial.
AB  - INTRODUCTION: The purpose of this 2-arm parallel study was to evaluate the
      dentoskeletal effects of rapid maxillary expansion with differential opening
      (EDO) compared with the hyrax expander in patients with complete bilateral cleft
      lip and palate. METHODS: A sample of patients with complete bilateral cleft lip
      and palate was prospectively and consecutively recruited. Eligibility criteria
      included participants in the mixed dentition with lip and palate repair performed
      during early childhood and maxillary arch constriction with a need for maxillary
      expansion before the alveolar bone graft procedure. The participants were
      consecutively divided into 2 study groups. The experimental and control groups
      comprised patients treated with rapid maxillary expansion using EDO and the hyrax
      expander, respectively. Cone-beam computed tomography examinations and digital
      dental models of the maxillary dental arches were obtained before expansion and 6
      months postexpansion. Standardized cone-beam computed tomography coronal sections
      were used for measuring maxillary transverse dimensions and posterior tooth
      inclinations. Digital dental models were used for assessing maxillary dental arch
      widths, arch perimeters, arch lengths, palatal depths, and posterior tooth
      inclinations. Blinding was used only during outcome assessment. The chi-square
      test was used to compare the sex ratios between groups (P <0.05). Intergroup
      comparisons were performed using independent t tests with the Bonferroni
      correction for multiple tests. RESULTS: Fifty patients were recruited and
      analyzed in their respective groups. The experimental group comprised 25 patients
      (mean age, 8.8 years), and the control group comprised 25 patients (mean age, 8.6
      years). No intergroup significant differences were found for age, sex ratio, and
      dentoskeletal variables before expansion. No significant differences were found
      between the EDO and the hyrax expander groups regarding skeletal changes. The EDO
      promoted significantly greater increases of intercanine width (difference, 3.63
      mm) and smaller increases in canine buccal tipping than the conventional hyrax
      expander. No serious harm was observed other than transitory variable pressure
      sensations on the maxillary alveolar process in both groups. CONCLUSIONS: The EDO
      produced skeletal changes similar to the conventional hyrax expander. The
      differential expander is an adequate alternative to conventional rapid maxillary
      expanders when there is need for greater expansion in the maxillary dental arch
      anterior region. REGISTRATION: This trial was not registered. PROTOCOL: The
      protocol was not published before trial commencement. FUNDING: This study
      received financial support from FAPESP (process number 2009/17622-9). As a
      possible conflict of interest, a patent with an EDO was submitted in March 2011
      to the National Institute of Industry Property and is still in process. However,
      we believe that this is a natural step of translational research (bench-to
      bedside), and we guarantee that the scientific results are true.

PMID- 27692415
TI  - Root resorption in Class II malocclusion treatment with Class II elastics.
AB  - INTRODUCTION: The objective of this investigation was to compare the amount of
      apical root resorption in nonextraction treatment of Class II malocclusions with
      and without Class II elastics. METHODS: A sample of 54 patients with Class II
      Division 1 malocclusion, retrospectively selected, was divided into 2 groups. The
      elastic group consisted of 27 patients who were exclusively treated with fixed
      appliances associated with elastics, and the headgear group consisted of 27
      patients treated with fixed appliances and extraoral headgear. The groups were
      matched regarding initial age, treatment time, amount of overjet, initial
      malocclusion severity, final occlusal status, and severity of Class II molar
      relationship. Posttreatment periapical radiographs of the maxillary and
      mandibular central and lateral incisors were used to evaluate root resorption.
      The amounts of resorption in the groups were compared with Mann-Whitney U tests.
      RESULTS: There was no statistically significant difference in the amounts of root
      resorption between the elastic and the headgear groups. CONCLUSION: Nonextraction
      treatment of Class II malocclusions with Class II elastics associated with fixed
      appliances causes similar root resorption as treatment with extraoral headgear
      and fixed appliances. Apical root resorption was predominantly mild and similar
      in the 2 groups.

PMID- 27692416
TI  - Mixed-methods assessment of perceptions of mandibular anterior malalignment and
      need for orthodontic retreatment.
AB  - INTRODUCTION: Postorthodontic occlusal changes may stem from true relapse or may
      be a consequence of characteristic temporal changes. The aims of this research
      were to identify occlusal discrepancies related to the mandibular labial segment
      prompting a decision to undergo orthodontic retreatment. METHODS: A mixed-methods
      assessment was undertaken comprising a qualitative analysis involving focus
      groups exploring the relative importance of a range of occlusal features in the
      decision to undergo retreatment and investigating the motives for seeking
      retreatment. Quantitative assessment of these occlusal discrepancies was
      undertaken by 50 lay and 50 professional raters. RESULTS: Several themes were
      identified in the qualitative analysis, with dental esthetics a major motive in
      seeking retreatment; variations in both the perception of relapse and retainer
      wear were identified. Horizontal irregularities of the mandibular anterior teeth
      were consistently perceived as the most severe. The professionals had slightly
      higher odds for suggesting the need for retreatment than did the laypeople,
      although this did not have statistical significance (odds ratio, 1.23; 95%
      confidence interval, 0.52-2.19; P = 0.65). CONCLUSIONS: The perception of
      mandibular labial segment irregularity and its influence on the need for
      orthodontic retreatment are complex and multifaceted. Nevertheless, horizontal
      discrepancies of the mandibular incisors were regarded as the most significant by
      both lay and professional raters.

PMID- 27692417
TI  - Objective method for evaluating orthodontic treatment from the lay perspective:
      An eye-tracking study.
AB  - INTRODUCTION: Currently, few methods are available to measure orthodontic
      treatment need and treatment outcome from the lay perspective. The objective of
      this study was to explore the function of an eye-tracking method to evaluate
      orthodontic treatment need and treatment outcome from the lay perspective as a
      novel and objective way when compared with traditional assessments. METHODS: The
      scanpaths of 88 laypersons observing the repose and smiling photographs of normal
      subjects and pretreatment and posttreatment malocclusion patients were recorded
      by an eye-tracking device. The total fixation time and the first fixation time on
      the areas of interest (eyes, nose, and mouth) for each group of faces were
      compared and analyzed using mixed-effects linear regression and a support vector
      machine. The aesthetic component of the Index of Orthodontic Treatment Need was
      used to categorize treatment need and outcome levels to determine the accuracy of
      the support vector machine in identifying these variables. RESULTS: Significant
      deviations in the scanpaths of laypersons viewing pretreatment smiling faces were
      noted, with less fixation time (P <0.05) and later attention capture (P <0.05) on
      the eyes, and more fixation time (P <0.05) and earlier attention capture (P
      <0.05) on the mouth than for the scanpaths of laypersons viewing normal smiling
      subjects. The same results were obtained when comparing posttreatment smiling
      patients, with less fixation time (P <0.05) and later attention capture on the
      eyes (P <0.05), and more fixation time (P <0.05) and earlier attention capture on
      the mouth (P <0.05). The pretreatment repose faces exhibited an earlier attention
      capture on the mouth than did the normal subjects (P <0.05) and posttreatment
      patients (P <0.05). Linear support vector machine classification showed
      accuracies of 97.2% and 93.4% in distinguishing pretreatment patients from normal
      subjects (treatment need), and pretreatment patients from posttreatment patients
      (treatment outcome), respectively. CONCLUSIONS: The eye-tracking device was able
      to objectively quantify the effect of malocclusion on facial perception and the
      impact of orthodontic treatment on malocclusion from the lay perspective. The
      support vector machine for classification of selected features achieved high
      accuracy of judging treatment need and treatment outcome. This approach may
      represent a new method for objectively evaluating orthodontic treatment need and
      treatment outcome from the perspective of laypersons.

PMID- 27692418
TI  - Craniofacial characteristics of children with mild hypodontia.
AB  - INTRODUCTION: The aim of our study was to evaluate the craniofacial
      characteristics of children with mild hypodontia using conventional and principal
      component (PC) analysis. METHODS: We used radiographic images of 124 children (8
      12 years old) with up to 4 missing teeth (55 boys, 69 girls) and of 676 reference
      children (365 boys, 311 girls) from the Rotterdam Generation R Study and the
      Nijmegen Growth Study in The Netherlands. Fifteen cephalometric measurements of
      children with hypodontia were compared with those of the reference children.
      Moreover, cephalometric parameters were combined into standardized PC scores
      using PC analysis, and the components were compared between the 2 groups.
      RESULTS: PC analysis showed common dental characteristics for all types of
      hypodontia: a significant increase of the interincisal angle, and decreases of
      the maxillary and mandibular incisor angles. Other findings were consistent when
      both methods were applied: (1) anterior hypodontia was significantly associated
      with the high-angle (hyperdivergent) craniofacial pattern, (2) the tendency
      toward a Class III malocclusion was identified in maxillary hypodontia, and (3)
      we observed a significant reduction of lower posterior facial height in children
      with posterior and mandibular hypodontia. CONCLUSIONS: Our findings suggest that
      children with mild hypodontia have distinctive skeletal and dental features.

PMID- 27692419
TI  - Tooth replacements in young adults with severe hypodontia: Orthodontic space
      closure, dental implants, and tooth-supported fixed dental prostheses. A follow
      up study.
AB  - INTRODUCTION: Children with severe hypodontia have a substantial impairment of
      their dental health starting early in life. The purpose of this study was to
      describe types and locations of substitutes for missing teeth in patients with
      severe hypodontia and to compare the crown and soft tissue morphologies of
      orthodontic space closure, dental implants, and tooth-supported fixed dental
      prostheses for replacing teeth in the anterior region. METHODS: Fifty patients
      missing 6 or more teeth and aged 18 years or older (mean age, 25.6 years) took
      part in a follow-up study. The patients were examined clinically with panoramic
      radiographs and clinical photographs. Crown and soft tissue variables (mucosal
      discoloration, crown morphology, color, and papilla index) were compared for
      orthodontic space closure, dental implant fixtures, and fixed dental prostheses.
      RESULTS: Dental implants, orthodontic space closure, and retaining deciduous
      teeth were the most commonly prescribed treatments. Persisting deciduous teeth
      showed a good survival rate at the follow-up examination. Mucosal discoloration
      was seen only for implant fixtures and was evident for almost all fixtures in the
      anterior mandible and two thirds of those in the anterior maxilla. The papilla
      index scored poorer for both implant fixtures and fixed dental prostheses
      compared with orthodontic space closure. CONCLUSIONS: Dental implants in the
      anterior region proved to be an inadequate treatment modality in patients with
      severe hypodontia because of pronounced mucosal discoloration.

PMID- 27692420
TI  - Dental esthetics and oral health-related quality of life in young adults.
AB  - INTRODUCTION: Dental esthetics affects how people are perceived by society and
      how they perceive themselves, and this may also affect their oral health-related
      quality of life (OHRQoL). The aim of this study was to compare the impacts of
      self-perceived and normatively assessed dental esthetics on the OHRQoL of a young
      adult population. METHODS: This was a cross-sectional descriptive study involving
      375 undergraduate university students, aged 18 to 30 years old. Data collection
      was carried out through oral examinations and self-administered questionnaires.
      Dental esthetics of the students was assessed using the esthetic component of the
      Index of Orthodontic Treatment Need. Two OHRQoL instruments were used: the
      shortened version of the Oral Health Impact Profile and the Psychosocial Impact
      of Dental Aesthetics Questionnaire. RESULTS: Statistically significant
      relationships (P <0.05) were recorded between both self-perceived and normatively
      assessed dental esthetics of the students, respectively, and 3 of the 4
      Psychosocial Impact of Dental Aesthetics Questionnaire subscales: dental self
      confidence (Kruskall-Wallis, P = 0.000; P = 0.000), psychological impact (P =
      0.003, P = 0.047), and esthetic concern (P = 0.006, P = 0.003). The only
      exception was the social impact subscale, in which a significant relationship was
      recorded only with self-perceived dental esthetics (P = 0.040). For the shortened
      version of the Oral Health Impact Profile scale, marked differences were also
      observed between the impacts recorded for both self-assessments and normative
      assessments, respectively, particularly for the psychological disability domain
      (Fisher exact test, P = 0.021, P = 0.000; P = 0.064, P = 0.096). CONCLUSIONS:
      Differences exist between the impacts of self-perceived and normatively assessed
      dental esthetics on the OHRQoL of young adults, particularly in the psychosocial
      domains. These differences should be considered in orthodontic treatment planning
      for young adult populations.

PMID- 27692421
TI  - Association between frontal sinus morphology and cervical vertebral maturation
      for the assessment of skeletal maturity.
AB  - INTRODUCTION: Various methods have been proposed to evaluate a patient's
      developmental status. However, most of them lacked precision and failed to give a
      reliable estimate of skeletal maturity. The aims of this study were to evaluate
      the association between frontal sinus morphology and cervical vertebral
      maturation for the assessment of skeletal maturity and to determine its validity
      in assessing the different stages of the adolescent growth spurt. METHODS: A
      cross-sectional study was performed on the pretreatment lateral cephalograms of
      252 subjects aged 8 to 21 years. The sample was divided into 6 groups based on
      the cervical vertebral maturation stages. The frontal sinus index was calculated
      by dividing the frontal sinus height and width, and the cervical stages were
      evaluated on the same radiograph. The Kruskal-Wallis test was applied to compare
      frontal sinus index values at different cervical stages, and the post hoc Dunnett
      T3 test was applied to compare frontal sinus index values between adjacent
      cervical stages for each sex. The Kendall tau-b values were computed to assess
      the correlation between the cervical stages and the sinus index. A P value of
      <=0.05 was considered statistically significant. RESULTS: The height and width of
      the frontal sinus were significantly larger in the male subjects than in the
      females. A significant association was found between the frontal sinus height and
      width and cervical stages (P <=0.001) in both sexes. However, the changes in the
      frontal sinus index across the different cervical stages were found to be
      significant (P <=0.001) in male subjects only. Similarly, a weak negative
      correlation was found between the sinus index and the cervical stages in male
      subjects (tau-b = -0.271; P <0.001), whereas no correlation was found in female
      subjects (tau-b = -0.006; P <0.928). However, the post hoc analysis showed that
      the values of the sinus index were comparable between any 2 adjacent cervical
      stages. CONCLUSIONS: The frontal sinus index cannot be used to identify the
      prepubertal, pubertal, and postpubertal stages of the adolescent growth spurt.
      Therefore, it cannot be used as a reliable maturity indicator.

PMID- 27692422
TI  - When static meets dynamic: Comparing cone-beam computed tomography and acoustic
      reflection for upper airway analysis.
AB  - INTRODUCTION: Upper airway measurement can be important for the diagnosis of
      breathing disorders. Acoustic reflection (AR) is an accepted tool for studying
      the airway. Our objective was to investigate the differences between cone-beam
      computed tomography (CBCT) and AR in calculating airway volumes and areas.
      METHODS: Subjects with prescribed CBCT images as part of their records were also
      asked to have AR performed. A total of 59 subjects (mean age, 15 +/- 3.8 years)
      had their upper airway (5 areas) measured from CBCT images, acoustic rhinometry,
      and acoustic pharyngometry. Volumes and minimal cross-sectional areas were
      extracted and compared with software. RESULTS: Intraclass correlation on 20
      randomly selected subjects, remeasured 2 weeks apart, showed high reliability (r
      >0.77). Means of total nasal volume were significantly different between the 2
      methods (P = 0.035), but anterior nasal volume and minimal cross-sectional area
      showed no differences (P = 0.532 and P = 0.066, respectively). Pharyngeal volume
      showed significant differences (P = 0.01) with high correlation (r = 0.755),
      whereas pharyngeal minimal cross-sectional area showed no differences (P =
      0.109). The pharyngeal volume difference may not be considered clinically
      significant, since it is 758 mm3 for measurements showing means of 11,000 +/-
      4000 mm3. CONCLUSIONS: CBCT is an accurate method for measuring anterior nasal
      volume, nasal minimal cross-sectional area, pharyngeal volume, and pharyngeal
      minimal cross-sectional area.

PMID- 27692423
TI  - Determination of soft tissue thickness at orthodontic miniscrew placement sites
      using ultrasonography for customizing screw selection.
AB  - INTRODUCTION: A wide variety of factors affect the success of orthodontic
      miniscrews in clinical situations, including thickness of the soft tissues. Our
      objectives were to assess area-related and sex-related differences in the soft
      tissue thicknesses of the buccal attached gingiva of the maxilla and the
      mandible, and the palatal masticatory mucosa at common orthodontic miniscrew
      placement sites, and to prescribe a guideline for miniscrew selection for a
      predictable clinical outcome. METHODS: The sample consisted of 32 randomly
      selected adults in the age group of 20 to 25 years. Soft-tissue thickness of the
      concerned areas was measured intraorally using an A-mode ultrasound transducer
      probe (Biomedix Optotechnik & Devices, Bangalore, India). Independent t tests,
      paired t tests, and 1-way analysis of variance with Duncan post hoc tests were
      used for statistical analysis. RESULTS: The palatal masticatory mucosa was 2 to 3
      times thicker than the corresponding buccal attached gingiva in both sexes. The
      thickness of the palatal masticatory mucosa in the midpalatal region was
      consistently less than 1 mm (range, 0.7-1 mm). The buccal attached gingiva was
      comparatively thicker in the maxilla than in the mandible, except for the
      mandibular molar regions. It also was found that the buccal attached gingiva was
      thicker in women in the maxillary anterior regions, whereas, the thickness was
      greater in the maxillary posterior regions in the men. CONCLUSIONS: Evaluating
      the soft tissue thicknesses before selecting an orthodontic miniscrew can help in
      providing a definite guide for orthodontists to select an appropriate screw in
      everyday clinical practice, further enhancing the predictability of miniscrew
      assisted orthodontics.

PMID- 27692424
TI  - Morphologic evaluation of dentoalveolar structures of mandibular anterior teeth
      during augmented corticotomy-assisted decompensation.
AB  - INTRODUCTION: Our aim in this study was to evaluate the effect of augmented
      corticotomy on the decompensation pattern of mandibular anterior teeth, alveolar
      bone, and surrounding periodontal tissues during presurgical orthodontic
      treatment. METHODS: Thirty skeletal Class III adult patients were divided into 2
      groups according to the application of augmented corticotomy labial to the
      anterior mandibular roots: experimental group (with augmented corticotomy, n =
      15) and control group (without augmented corticotomy, n = 15). Lateral
      cephalograms and cone-beam computed tomography images were taken before
      orthodontic treatment and before surgery. The measurements included the
      inclination and position of the mandibular incisors, labial alveolar bone area,
      vertical alveolar bone height, root length, and alveolar bone thickness at 3
      levels surrounding the mandibular central incisors, lateral incisors, and
      canines. RESULTS: The mandibular incisors were significantly proclined in both
      groups (P <0.001); however, the labial movement of the incisor tip was greater in
      the experimental group (P <0.05). Significant vertical alveolar bone loss was
      observed only in the control group (P <0.001). The middle and lower alveolar
      thicknesses and labial alveolar bone area increased in the experimental group. In
      the control group, the upper and middle alveolar thicknesses and labial alveolar
      bone area decreased significantly. There were no significant differences in
      dentoalveolar changes between the 3 kinds of anterior teeth in each group, except
      for root length in the experimental group (P <0.05). CONCLUSIONS: Augmented
      corticotomy provided a favorable decompensation pattern of the mandibular
      incisors, preserving the periodontal structures surrounding the mandibular
      anterior teeth for skeletal Class III patients.

PMID- 27692425
TI  - Orthodontic treatment and follow-up of a patient with cerebral palsy and spastic
      quadriplegia.
AB  - INTRODUCTION: This report describes the clinical orthodontic management of a
      patient with spastic quadriplegia and cerebral palsy. Guidelines to overcome
      difficulties encountered during the treatment period are suggested. METHODS: A 13
      year-old boy with cerebral palsy and spastic quadriplegia complained of an
      undesirable oral appearance because of his malocclusion. He had a Class II molar
      relationship, with severe maxillary and moderate mandibular anterior crowding.
      Enamel hypoplasia was apparent on all teeth. He had losses of body function and
      upper extremity function of 70% and 39%, respectively. His physical limitations
      necessitated a treatment approach that did not rely on patient-dependent
      appliances. The treatment plan called for maxillary first premolar extractions,
      mandibular incisor protrusion, and air rotor stripping. RESULTS: The patient's
      oral function and esthetic appearance were significantly improved. Aligned dental
      arches with good occlusion were obtained. The patient's self-confidence improved
      during the treatment period. CONCLUSIONS: Physical appearance can influence
      personality and social acceptability. Corrective orthodontic treatment for
      patients with physical handicaps can improve not only oral function, but also
      self-confidence and self-esteem.

PMID- 27692426
TI  - Adult skeletal Class II high-angle case treated with a fully customized lingual
      bracket appliance.
AB  - To achieve optimum occlusal and facial results in a patient with high-angle
      maxillary protrusion, it is important to move Point A back with retraction of the
      anterior teeth and prevent clockwise rotation of the mandible through good
      vertical control. A woman, aged 42 years 5 months, with a protrusive profile
      sought lingual orthodontic treatment. She had a skeletal Class II high-angle
      pattern with maxillary protrusion and mandibular retrusion. The extraction of the
      4 first premolars was indicated to correct the problems. The vertical bowing
      effect, a side effect known to occur with conventional lingual bracket systems
      owing to torque loss, would preclude adequate retraction of Point A and
      compromise the facial results. To prevent this issue, a fully customized lingual
      bracket system with vertical slots for the anterior teeth using ribbon-wise
      archwires was selected. A midpalatal miniscrew was used to prevent molar
      extrusion. As a result, the bodily retraction of the maxillary incisors and Point
      A was achieved, obtaining an attractive facial profile.

PMID- 27692427
TI  - Forced eruption of impacted maxillary central incisors with severely dilacerated
      roots.
AB  - Treatment of impacted dilacerated incisors is challenging for clinicians because
      of the prominent position of the teeth and the abnormality of their roots. We
      report on 2 patients who had horizontally upward impacted and severely
      dilacerated maxillary central incisors. The first patient's root perforated the
      labial plate without significant resorption, and the second patient's root was
      resorbed. Both patients were treated by a surgical-orthodontic approach, and the
      crowns of the impacted teeth were brought into the arches by closed forced
      eruption. Therefore, if impacted teeth have dilacerated roots, patients should be
      told of the possibility of root resorption.

PMID- 27692428
TI  - New algorithm for semiautomatic segmentation of nasal cavity and pharyngeal
      airway in comparison with manual segmentation using cone-beam computed
      tomography.
AB  - INTRODUCTION: Our objectives were to assess reliability, validity, and time
      efficiency of semiautomatic segmentation using Segura software of the nasal and
      pharyngeal airways, against manual segmentation with point-based analysis with
      color mapping. METHODS: Pharyngeal and nasal airways from 10 cone-beam computed
      tomography image sets were segmented manually and semiautomatically using Segura
      (University of Alberta, Edmonton, Alberta, Canada). To test intraexaminer and
      interexaminer reliabilities, semiautomatic segmentation was repeated 3 times by 1
      examiner and then by 3 examiners. In addition to volume and surface area, point
      based analysis was completed to assess the reconstructed 3-dimensional models
      from Segura against manual segmentation. The times of both methods of
      segmentation were also recorded to assess time efficiency. RESULTS: The
      reliability and validity of Segura were excellent (intraclass correlation
      coefficient, >0.9 for volume and surface area). Part analysis showed small
      differences between the Segura and manually segmented 3-dimensional models
      (greatest difference did not exceed 4.3 mm). Time of segmentation using Segura
      was significantly shorter than that for manual segmentation, 49 +/- 11.0 vs 109
      +/- 9.4 minutes (P <0.001). CONCLUSIONS: Semiautomatic segmentation of the
      pharyngeal and nasal airways using Segura was found to be reliable, valid, and
      time efficient. Part analysis with color mapping was the key to explaining
      differences in upper airway volume and provides meaningful and clinically
      relevant analysis of 3-dimensional changes.

PMID- 27692429
TI  - Familiarity, of sorts.

PMID- 27692430
TI  - The 2 * 2 tabulation.

PMID- 27692432
TI  - Increased activity of lysozyme and complement system in Atlantic halibut exposed
      to elevated CO2 at six different temperatures.
AB  - Ocean acidification and rising seawater temperature are environmental stressors
      resulting from the continuous increase of the atmospheric CO2 concentration due
      to anthropogenic activities. As a consequence, marine fish are expected to
      undergo conditions outside of their tolerance range, leading to physiological
      challenges with possible detrimental implications. Our research group has
      previously shown that exposure to elevated CO2 modulated the immune system of the
      Atlantic halibut. To further investigate this finding, we analysed non-specific
      immune components in blood plasma of Atlantic halibut (Hippoglossus hippoglossus)
      juveniles acclimated to six different temperatures (5, 10, 12, 14, 16 and 18 
      degrees C), and to water pH of 8.0 (control) or 7.6 (predicted for year 2100) for
      three months. Plasma ions (K+, Na+, Ca++, Cl-) and lactate concentrations were
      also measured. The analysis of plasma ions did not show any trends related to
      temperature or CO2 exposure, and the majority of the experimental fish were able
      to maintain ionic balance. The results show that both innate immune components
      (lysozyme and alternative complement system) had increased activities in response
      to elevated CO2, representing a CO2-related impact on the halibut's immune
      system. The increased activity of lysozyme and complement system is possibly part
      of the acclimatization process, and might be protective.

PMID- 27692431
TI  - The Chromatin Landscape of Cellular Senescence.
AB  - Cellular senescence, an irreversible growth arrest triggered by a variety of
      stressors, plays important roles in normal physiology and tumor suppression, but
      accumulation of senescent cells with age contributes to the functional decline of
      tissues. Senescent cells undergo dramatic alterations to their chromatin
      landscape that affect genome accessibility and their transcriptional program.
      These include the loss of DNA-nuclear lamina interactions, the distension of
      centromeres, and changes in chromatin composition that can lead to the activation
      of retrotransposons. Here we discuss these findings, as well as recent advances
      in microscopy and genomics that have revealed the importance of the higher-order
      spatial organization of the genome in defining and maintaining the senescent
      state.

PMID- 27692434
TI  - Utility of anti-factor Xa monitoring in surgical patients receiving prophylactic
      doses of enoxaparin for venous thromboembolism prophylaxis.
AB  - BACKGROUND: Between 2% and 10% of the highest risk surgery, patients have a
      "breakthrough" venous thromboembolism (VTE) event despite receipt of
      chemoprophylaxis. The goals of this review are to summarize how patient-level
      factors may predict enoxaparin metabolism and how alterations in enoxaparin dose
      magnitude and frequency affect both anti-factor Xa (aFXa) levels and downstream
      VTE events. DATA SOURCES: Relevant articles were identified on PubMed. Fixed-dose
      prophylaxis provides inadequate enoxaparin prophylaxis for most surgical patients
      based on anti-factor Xa levels. Inadequate enoxaparin dosing has been correlated
      with both asymptomatic and symptomatic VTE events. Patient-level factors such as
      gross weight and extent of injury predict enoxaparin metabolism. Weight-based or
      weight-tiered dosing regimens-and real-time dose adjustment based on anti-factor
      Xa levels-allow an increased proportion of patients to have in-range anti-factor
      Xa levels. CONCLUSIONS: Inadequate enoxaparin dosing may explain why some
      patients have VTE despite enoxaparin prophylaxis. Ongoing research in the utility
      of weight-based or anti-factor Xa level driven enoxaparin dosing and dose
      adjustment is reasonable.

PMID- 27692433
TI  - Moderating effects of immunosuppressive medications and risk factors for post
      operative joint infection following total joint arthroplasty in patients with
      rheumatoid arthritis or osteoarthritis.
AB  - OBJECTIVE: Inconclusive findings about infection risks, importantly the use of
      immunosuppressive medications in patients who have undergone large-joint total
      joint arthroplasty, challenge efforts to provide evidence-based perioperative
      total joint arthroplasty recommendations to improve surgical outcomes. Thus, the
      aim of this study was to describe risk factors for developing a post-operative
      infection in patients undergoing TJA of a large joint (total hip arthroplasty,
      total knee arthroplasty, or total shoulder arthroplasty) by identifying clinical
      and demographic factors, including the use of high-risk medications (i.e.,
      prednisone and immunosuppressive medications) and diagnoses [i.e., rheumatoid
      arthritis (RA), osteoarthritis (OA), gout, obesity, and diabetes mellitus] that
      are linked to infection status, controlling for length of follow-up. METHODS: A
      retrospective, case-control study (N = 2212) using de-identified patient health
      claims information from a commercially insured, U.S. dataset representing 15
      million patients annually (from January 1, 2007 to December 31, 2009) was
      conducted. Descriptive statistics, t-test, chi-square test, Fisher's exact test,
      and multivariate logistic regression were used. RESULTS: Male gender (OR = 1.42,
      p < 0.001), diagnosis of RA (OR = 1.47, p = 0.031), diabetes mellitus (OR = 1.38,
      p = 0.001), obesity (OR = 1.66, p < 0.001) or gout (OR = 1.95, p = 0.001), and a
      prescription for prednisone (OR = 1.59, p < 0.001) predicted a post-operative
      infection following total joint arthroplasty. Persons with post-operative joint
      infections were significantly more likely to be prescribed allopurinol (p =
      0.002) and colchicine (p = 0.006); no significant difference was found for the
      use of specific disease-modifying anti-rheumatic drugs and TNF-alpha inhibitors.
      CONCLUSION: High-risk, post-operative joint infection groups were identified
      allowing for precautionary clinical measures to be taken.

PMID- 27692435
TI  - The milk we drink, food for thought.

PMID- 27692436
TI  - New automated antimullerian hormone assays are more reliable than the manual
      assay in patients with reduced antral follicle count.
AB  - OBJECTIVE: To compare the strength of the relationship between antral follicle
      count (AFC) and serum antimullerian hormone (AMH) concentrations obtained with
      two automated and one manual AMH assays in three different AFC populations.
      DESIGN: Prospective cohort study. SETTING: University-affiliated IVF-ET center.
      PATIENT(S): Frozen-thawed serum samples of 211 assisted conception candidates,
      aged 24-43 years. INTERVENTION(S): Serum AMH was measured using one manual (AMH
      Gen II) and two fully automated (Access AMH and Elecsys AMH) assays. Antral
      follicle count was performed under strictly standardized conditions and sorted
      into three groups according to tercile values: low AFC (3-12 follicles; n = 73),
      intermediate AFC (13-20 follicles; n = 65), and high AFC (21-84 follicles; n =
      73). MAIN OUTCOME MEASURE(S): Strength of correlation between AMH levels and AFC.
      RESULT(S): Overall, AMH levels were lower with Access AMH (-16%) and Elecsys AMH
      (-20%) than with AMH Gen II. Remarkably, the strength of correlations between AFC
      and circulating AMH levels was the same with the three assays (r = 0.83). Yet in
      the low AFC group, serum AMH levels obtained by Access AMH and Elecsys AMH showed
      a stronger correlation with AFC (r = 0.63 and r = 0.65, respectively) than the
      AMH Gen II (r = 0.52), a phenomenon that was not observed in the remaining AFC
      groups. CONCLUSION(S): As compared with conventional AMH Gen II assay results,
      [1] serum AMH concentrations were -16% and -20% lower with Access AMH and Elecsys
      AMH, respectively; and [2] automated assays were more strongly correlated to AFC
      in the subset of patients with reduced follicle count.

PMID- 27692437
TI  - Why do euploid embryos miscarry? A case-control study comparing the rate of
      aneuploidy within presumed euploid embryos that resulted in miscarriage or live
      birth using next-generation sequencing.
AB  - OBJECTIVE: To determine whether undetected aneuploidy contributes to pregnancy
      loss after transfer of euploid embryos that have undergone array comparative
      genomic hybridization (aCGH). DESIGN: Case-control study. SETTING: University
      based fertility center. PATIENT(S): Cases included 38 patients who underwent
      frozen euploid ET as determined by aCGH, resulting in miscarriage. Controls
      included 38 patients who underwent frozen euploid ET as determined by aCGH,
      resulting in a live birth. INTERVENTION(S): Next-generation sequencing (NGS)
      protocols were internally validated. Saved amplified DNA samples from the
      blastocyst trophectoderm biopsies previously diagnosed as euploid by aCGH were
      reanalyzed using NGS. Cytogenetic reports of the products of conception for 20 of
      the pregnancies resulting in miscarriage were available for comparison. MAIN
      OUTCOME MEASURE(S): The incidence of aneuploidy and mosaicism using NGS within
      embryos resulting in miscarriage and live birth. RESULT(S): Of euploid embryos
      analyzed by aCGH resulting in miscarriage, 31.6% were mosaic and 5.2% were
      polyploid by NGS. The rate of chromosomal abnormalities was significantly higher
      in embryos resulting in miscarriage (36.8%) than in those resulting in live
      births (15.8%). The rate of mosaicism was twice as high among embryos resulting
      in miscarriage than those resulting in live birth, but this was not statistically
      significant. Next-generation sequencing detected more cases of mosaicism than
      cytogenetic analysis of products of conception. CONCLUSION(S): Undetected
      aneuploidy may increase the risk of first trimester pregnancy loss. Next
      generation sequencing may detect mosaicism and triploidy more frequently than
      aCGH, which could help to identify embryos at high risk of miscarriage. Mosaic
      embryos, however, should not be discarded as some can result in live births.

PMID- 27692439
TI  - CVD-grown monolayer graphene induces osteogenic but not odontoblastic
      differentiation of dental pulp stem cells.
AB  - OBJECTIVE: The objective was to investigate the potential of graphene (Gp) to
      induce odontogenic and osteogenic differentiation in dental pulp stem cells
      (DPSC). METHODS: Gp was produced by chemical vapor deposition. DPSC were seeded
      on Gp or glass (Gl). Cells were maintained in culture medium for 28 days. Every
      two days, culture medium from Gp was used to treat cells on Gl and vice versa.
      Mineralization and differentiation of DPSC on all substrates were evaluated after
      14 and 28 days by alizarin red S staining, qPCR, immunofluorescence and FACS.
      Statistics were performed with two-way ANOVA and multiple comparisons were
      performed using Tukey's post hoc test at a pre-set significance level of 5%.
      RESULTS: After 14 and 28 days, Gp induced higher levels of mineralization as
      compared to Gl. Odontoblastic genes (MSX-1, PAX and DMP) were down-regulated and
      osteogenic genes and proteins (RUNX2, COL and OCN) were significantly upregulated
      on Gp comparing to Gl (p<0.05 for all cases). Medium from Gp induced
      downregulation of odontoblastic genes and increased bone-related gene and protein
      on Gl. SIGNIFICANCE: Graphene induced osteogenic and not odontoblastic
      differentiation of DPSC without the use of chemical inducers for osteogenesis.
      Graphene has the potential to be used as a substrate for craniofacial bone tissue
      engineering research.

PMID- 27692438
TI  - Bovine tooth is a substitute for human tooth on bond strength studies: A
      systematic review and meta-analysis of in vitro studies.
AB  - OBJECTIVES: This study aimed to systematically review the literature to compare
      the bond strength values achieved from human and bovine teeth of in vitro
      studies. DATA AND SOURCE: The PubMed/MEDLINE, ISI Web of Science and Scopus
      electronic databases were searched to select laboratorial studies that evaluated
      adhesive systems bond strength to human and bovine teeth. No publication year or
      language restriction was considered. STUDY SELECTION: From 1,285 potentially
      eligible studies, 15 were selected for full-text analysis, 11 were included in
      the systematic review and 9 in the meta-analysis. Two authors independently
      selected the studies, extracted the data and assessed the risk of bias. Mean
      differences were obtained by comparing bond strength values between human and
      bovine teeth (overall analysis), and considering enamel and dentin separately
      (subgroups analysis). Statistical analysis was performed using RevMan5.1, with
      random effects model, at a significance level of p=0.05. RESULTS: No significant
      difference was found between human and bovine teeth (p=0.35), either for enamel
      (p=0.07) or for dentin (p=0.93) substrates. Low to moderate heterogeneity was
      found on the meta-analysis. All included studies in the systematic review scored
      between medium and high risk of bias. CONCLUSIONS: Bovine teeth can be a reliable
      substitute for human ones on bond strength studies of adhesive systems to both
      enamel and dentin substrates.

PMID- 27692441
TI  - Successful Hemodialysis Arteriovenous Fistula Creation in a Patient With
      Continuous-Flow Left Ventricular Assist Device Support.
AB  - Heart failure necessitating left ventricular assist device (LVAD) support can
      lead to kidney failure requiring dialysis. Some of these patients may require
      long-term hemodialysis (HD). Optimal vascular access for a patient on long-term
      HD therapy with an LVAD remains a complex issue. The majority of LVADs are of the
      continuous-flow type, and it has been theorized that native arteriovenous fistula
      maturation may be impaired in a setting of decreased pulsatile arterial flow. We
      describe a case of successful creation and use of an arteriovenous fistula in an
      HD-dependent patient with a continuous-flow LVAD.

PMID- 27692440
TI  - Gender gap in medical care in ST segment elevation myocardial infarction
      networks: Findings from the Catalan network Codi Infart.
AB  - OBJECTIVE: To assess the impact of gender upon the prognosis and medical care in
      a regional acute ST-elevation myocardial infarction management network. DESIGN:
      An observational study was made of consecutive patients entered in a prospective
      database. SCOPE: The Catalan acute ST-elevation myocardial infarction management
      network. PATIENTS: Patients treated between January 2010 and December 2011.
      INTERVENTIONS: Primary angioplasty, thrombolysis or conservative management.
      VARIABLES OF INTEREST: Time intervals, proportion and type of reperfusion,
      overall mortality, and in-hospital complication and overall mortality at 30 days
      and one year were compared in relation to gender. RESULTS: Of the 5,831 patients
      attended by the myocardial infarction network, 4,380 had a diagnosis of acute ST
      elevation myocardial infarction, and 961 (21.9%) were women. Women were older
      (69.8+/-13.4 vs. 60.6+/-12.8 years; P<.001), had a higher prevalence of diabetes
      (27.1 vs. 18.1%, P<.001), Killip class>I (24.9 vs. 17.3%; P<.001) and no
      reperfusion (8.8 vs. 5.2%; P<.001) versus men. In addition, women had greater
      delays in medical care (first medical contact-to-balloon: 132 vs. 122min; P<.001,
      and symptoms onset-to-balloon: 236 vs. 210min; P<.001). Women presented higher
      percentages of overall in-hospital complications (20.6 vs. 17.4%; P=.031), in
      hospital mortality (4.8 vs. 2.6%; P=.001), 30-day mortality (9.1 vs. 4.5%;
      P<.001) and one-year mortality (14.0 vs. 8.3%; P<.001) versus men. Nevertheless,
      after multivariate adjustment, no gender differences in 30-day and one-year
      mortality were observed. CONCLUSIONS: Despite a higher risk profile and poorer
      medical management, women present similar 30-day and one-year outcomes as their
      male counterparts in the context of the myocardial infarction management network.

PMID- 27692442
TI  - Hypophosphatemia in Users of Cannabis.
AB  - As cannabis use has legalized for medical and recreational use in several states,
      the medical community has become more aware of the drug's potential toxicities.
      First described in 2004, cannabinoid hyperemesis syndrome is increasingly
      recognized as a cause of hospitalization among drug users. However, little
      information is available in the medical literature regarding electrolyte
      abnormalities in this syndrome. Between 2011 and 2014, six men were treated for
      cannabinoid hyperemesis syndrome at the Veterans Affairs Medical Center in San
      Diego, CA, and found to have significant hypophosphatemia (phosphate range, <1
      1.3mg/dL). The 6 cases are presented here and possible causes of hypophosphatemia
      are discussed. In 3 patients, serum phosphate levels normalized spontaneously
      within hours, suggesting redistribution of phosphate as a potential mechanism.
      Hyperventilation, which can lead to phosphate redistribution, was observed in 4
      of the 6 individuals and may have contributed. Hypophosphatemia is a presenting
      feature of cannabinoid hyperemesis syndrome in some patients.

PMID- 27692443
TI  - How to peer review and revise manuscripts submitted for publication in academic
      nursing journals.

PMID- 27692444
TI  - Basics of Confocal Microscopy and the Complexity of Diagnosing Skin Tumors: New
      Imaging Tools in Clinical Practice, Diagnostic Workflows, Cost-Estimate, and New
      Trends.
AB  - The use of reflectance confocal microscopy (RCM) and other noninvasive imaging
      devices can potentially streamline clinical care, leading to more precise and
      efficient management of skin cancer. This article explores the potential role of
      RCM in cutaneous oncology, as an adjunct to more established techniques of
      detecting and monitoring for skin cancer, such as dermoscopy and total body
      photography. Discussed are current barriers to the adoption of RCM, diagnostic
      workflows and standards of care in the United States and Europe, and medicolegal
      issues. The potential role of RCM and other similar technological innovations in
      the enhancement of dermatologic care is evaluated.

PMID- 27692445
TI  - Opening a Window into Living Tissue: Histopathologic Features of Confocal
      Microscopic Findings in Skin Tumors.
AB  - The knowledge of histopathology and in vivo reflectance confocal microscopy
      correlation has several potential applications. Reflectance confocal microscopy
      can be performed in all skin tumors, and in this article, the most common
      histopathologic features of confocal microscopic findings in melanocytic skin
      tumors and nonmelanocytic skin tumors are described.

PMID- 27692446
TI  - Discriminating Nevi from Melanomas: Clues and Pitfalls.
AB  - Reflectance confocal microscopy (RCM) together with dermoscopy enables improved
      differentiation of melanomas from most nevi. The resulting high sensitivity for
      detecting melanoma with RCM is complemented by a concomitant increased
      specificity, which results in the reduction of unnecessary biopsies of nevi.
      Although RCM can achieve high diagnostic accuracy for early melanoma detection,
      false-negative and false-positive cases of melanoma are occasionally encountered.
      This article reviews the essential clues and pitfalls for the diagnosis of
      melanoma via RCM and highlights the importance of evaluating RCM findings in
      light of the clinical scenario and dermoscopic features.

PMID- 27692447
TI  - Melanomas.
AB  - Melanomas are a wide range of tumors that differ in their epidemiology,
      morphology, genetic profile, and biological behavior. They can be grouped as
      superficial spreading melanoma, lentigo maligna, and nodular melanoma.
      Reflectance confocal microscopy is useful for the evaluation of skin lesions that
      are dermoscopically doubtful by increasing diagnostic accuracy and specificity.
      This article provides a comprehensive overview of the different confocal main
      morphologies of distinct melanoma types as a function of the anatomic location of
      the tumor.

PMID- 27692448
TI  - Lentigo Maligna, Macules of the Face, and Lesions on Sun-Damaged Skin: Confocal
      Makes the Difference.
AB  - Distinguishing lentigo maligna (LM) and lentigo maligna melanoma (LMM) from
      background pigmented non-melanoma lesions is challenging. The field of solar
      damage can obscure clinical assessment, and diagnostic ambiguities are created
      due to the overlap of the clinical features of LM with other benign lesions.
      Moreover, margin assessment on histology is limited by the resemblance between
      melanocytic hyperplasia of actinically damaged skin and scattered atypical
      melanocytes of LM/LMM. Dermoscopy has made a significant contribution but is
      often not sufficient for diagnosis and margin assessment. Confocal microscopy has
      become an important complementary tool in enhancing the management of these
      complex lesions.

PMID- 27692449
TI  - Glowing in the Dark: Use of Confocal Microscopy in Dark Pigmented Lesions.
AB  - Reflectance confocal microscopy patterns and structures of clinically dark
      lesions are described. Because many of the dark lesions have melanin in
      superficial skin layers these lesions show great semiology by confocal.
      Limitations and pitfalls of reflectance confocal microscopy in clinically dark
      lesions are also detailed.

PMID- 27692450
TI  - Enlightening the Pink: Use of Confocal Microscopy in Pink Lesions.
AB  - Solitary pink lesions can pose a particular challenge to dermatologists because
      they may be almost or completely featureless clinically and dermoscopically,
      previously requiring biopsy to exclude malignancy. However, these lesions usually
      are not particularly challenging histopathologically. Thus, the incorporation of
      in vivo reflectance confocal microscopy into the clinical practice, which allows
      for noninvasive examination of the skin at the cellular level revealing features
      previously seen only on histopathology, is particularly useful for this subset of
      clinically difficult lesions.

PMID- 27692451
TI  - Shining into the White: The Spectrum of Epithelial Tumors from Actinic Keratosis
      to Squamous Cell Carcinoma.
AB  - Actinic keratosis, Bowen disease, and invasive squamous cell carcinoma represent
      different steps within the disease continuum of squamous neoplasia. Although
      these stages of squamous neoplasia share common findings, reflectance confocal
      microscopy may be applied for their differentiation and distinction from other
      benign or malignant lesions. Hyperkeratosis represents the most important
      limitation in the evaluation of squamous neoplasia as it may impair the analysis
      of deeper epidermal and dermal structures significantly.

PMID- 27692452
TI  - Application of Handheld Confocal Microscopy for Skin Cancer Diagnosis: Advantages
      and Limitations Compared with the Wide-Probe Confocal.
AB  - The clinical diagnosis of tumors on the curved surfaces of the face, around the
      eyes, and on the mucosal surfaces can be difficult, while biopsies and excisions
      can have functional and aesthetic consequences. To avoid unnecessary surgery,
      clinicians have been aiming to attain accurate noninvasive diagnosis of lesions
      at these sites. However, acquisition of high-quality images with dermoscopy and
      with traditional wide-probe reflectance confocal microscopy (WP-RCM) have been
      hampered with technical difficulties. This article discusses the technical
      parameters of the handheld reflectance confocal microscope and discusses its
      advantages and limitations compared with the WP-RCM.

PMID- 27692453
TI  - Confocal Microscopy for Special Sites and Special Uses.
AB  - This article describes the use of confocal microscopy for special sites and
      unconventional applications. These new applications have been made possible
      thanks to the introduction on the market of a hand-held camera. Special sites
      discussed include mucosa, nails, and palms and soles. Special uses discussed
      include infections and infestations; tumor mapping; understanding clinical,
      dermoscopic, and histology features; videos and ex vivo confocal microscopy.

PMID- 27692454
TI  - Reflectance Confocal Microscopy Algorithms for Inflammatory and Hair Diseases.
AB  - Reflectance confocal microscopy (RCM) allows real-time, noninvasive microscopic
      view of the skin at nearly histologic resolution serially over time. RCM
      increases the sensibility and sensitivity of the diagnosis of skin tumours. RCM
      evaluates descriptive features of psoriasis, lupus erythematosus, contact
      dermatitis, and others. Three groups of optical histology have been described:
      psoriasiform, spongiotic, and interface dermatitis. In a multicenter study, RCM
      patterns of spongiotic, hyperkeratotic, and interface dermatitis have been
      analyzed and an algorithmic method of analysis for fast application in the
      clinical setting based on a multivariate analysis has been proposed. A tree
      decision diagram has been also established.

PMID- 27692456
TI  - Telediagnosis with Confocal Microscopy: A Reality or a Dream?
AB  - Reflectance confocal microscopy (RCM) is becoming more popular among
      dermatologists aiming to improve their bedside diagnostic accuracy and reduce
      unnecessary removal of benign cutaneous lesions. With increased interest in the
      field, limitation of experts, and dedicated training programs, telemedicine
      application to RCM (teleconfocal) helps to connect patients with experts at a
      distance. Diagnostic accuracy of store-and-forward telemedicine review of RCM
      images, patient safety, and cost-effectiveness are important considerations for
      proper acceptance and usage of the technology in the medical community.

PMID- 27692455
TI  - In Vivo and Ex Vivo Confocal Microscopy for Dermatologic and Mohs Surgeons.
AB  - Confocal microscopy is a modern imaging device that has been extensively applied
      in skin oncology. More specifically, for tumor margin assessment, it has been
      used in two modalities: reflectance mode (in vivo on skin patient) and
      fluorescence mode (on freshly excised specimen). Although in vivo reflectance
      confocal microscopy is an add-on tool for lentigo maligna mapping, fluorescence
      confocal microscopy is far superior for basal cell carcinoma and squamous cell
      carcinoma margin assessment in the Mohs setting. This article provides a
      comprehensive overview of the use of confocal microscopy for skin cancer margin
      evaluation.

PMID- 27692457
TI  - Well-aging: Early Detection of Skin Aging Signs.
AB  - The aim of the current review is to provide an overview of the use of reflectance
      confocal microscopy to detect early skin aging signs. This new imaging tool holds
      the promise to morphologically explore the epidermis and upper dermis at nearly
      histologic resolution and over time. The main confocal findings of aged skin
      include the presence of irregular honeycombed pattern, linear skin furrows,
      mottled pigmentation, and distinct collagen types (coarse and huddled).

PMID- 27692458
TI  - The Role of Reflectance Confocal Microscopy in Clinical Trials for Tumor
      Monitoring.
AB  - Reflectance confocal microscopy (RCM) allows the evaluation with superb accuracy
      of some skin tumors before, during, and after treatment. In clinical trials RCM
      has been shown to provide useful information for evaluation of efficacy of
      topical or systemic medication. With the recent introduction of handheld RCM a
      fast examination of the tumor can be done in minutes. In patients treated with
      surgery RCM plays a unique role to precisely map margins of the tumor in the skin
      surface and for the detection of subclinical recurrences. This article reviews
      the use of RCM in the research of different skin cancer tumor treatments.

PMID- 27692459
TI  - Fluorescence (Multiwave) Confocal Microscopy.
AB  - In addition to reflectance confocal microscopy, multiwave confocal microscopes
      with different laser wavelengths in combination with exogenous fluorophores allow
      fluorescence mode confocal microscopy in vivo and ex vivo. Fluorescence mode
      confocal microscopy improves the contrast between the epithelium and the
      surrounding soft tissue and allows the depiction of certain structures, like
      epithelial tumors, nerves, and glands.

PMID- 27692460
TI  - Reflectance Confocal Microscopy Clinical Applications: The Skin from Inside.

PMID- 27692462
TI  - Early-Term Birth in Single-Ventricle Congenital Heart Disease After the Fontan
      Procedure: Neurodevelopmental and Psychiatric Outcomes.
AB  - OBJECTIVES: To investigate the long-term impact of early-term birth (37-38 weeks'
      gestation) relative to full-term birth (>=39 weeks' gestation) on
      neurodevelopmental and psychiatric outcomes in adolescents with single-ventricle
      congenital heart disease (CHD). STUDY DESIGN: This cross-sectional cohort study
      analyzed retrospective medical records from full term adolescents with single
      ventricle CHD who underwent the Fontan procedure. Participants underwent
      neurodevelopmental and psychiatric evaluations, as well as structural brain
      magnetic resonance imaging. Early-term born adolescents were compared with full
      term born adolescents using regression models with adjustments for family social
      status, birth weight, and genetic abnormality status. Medical and demographic
      risk factors were examined as well. RESULTS: Compared with the full-term group (n
      = 100), adolescents born early term (n = 33) scored significantly worse on daily
      life executive functions, as measured by the Behavior Rating Inventory of
      Executive Function parent-report (mean scores: early term, 62.0 +/- 10.9; full
      term, 55.6 +/- 12.2; P = .009) and self-report (P = .02) composites. Adolescents
      born early term were more likely than those born full term to have a lifetime
      attention-deficit/hyperactivity disorder (ADHD) diagnosis (early term, 55%; full
      term, 26%; P = .001). The early-term group also displayed greater psychiatric
      symptom severity, as indicated by the clinician-reported Brief Psychiatric Rating
      Scale (mean score: early term, 16.1 +/- 8.6; full-term, 12.5 +/- 8.2; P = .007).
      CONCLUSION: Early-term birth is associated with greater prevalence of executive
      dysfunction, ADHD diagnosis, and psychiatric problems in adolescents with single
      ventricle CHD. Early-term birth should be included as a potential risk factor in
      the algorithm for closer developmental surveillance in CHD.

PMID- 27692464
TI  - Long-Term Outcome of Classic and Incomplete PFAPA (Periodic Fever, Aphthous
      Stomatitis, Pharyngitis, and Adenitis) Syndrome after Tonsillectomy.
AB  - OBJECTIVE: To compare the effectiveness of tonsillectomy and the long-term
      outcome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA)
      syndrome in patients fulfilling the classic diagnostic criteria and in those with
      regularly recurring fever as the only symptom or with onset of symptoms after age
      5 years or both. STUDY DESIGN: We reviewed the medical records of 3852 children
      who underwent tonsillectomy between 1990 and 2007 and identified 108 children who
      did so because of regularly recurring fevers. The patients were invited to an
      outpatient visit and were classified into 2 groups: those who met (N = 58) and
      those who did not meet (N = 50) Thomas diagnostic criteria. We then compared the
      clinical profile and outcome of PFAPA symptoms after tonsillectomy between the 2
      groups. RESULTS: In the group that met Thomas criteria, 97% (56/58) had complete
      resolution of fever episodes after tonsillectomy; in the group that did not meet
      Thomas criteria (50/50) had complete resolution of fever episodes after
      tonsillectomy (P = .25). The clinical profile of the periodic fevers and the
      occurrence of other illnesses during follow-up were similar in both groups.
      Thomas criteria identified 56 of 106 patients responding to tonsillectomy.
      CONCLUSIONS: Tonsillectomy was an effective treatment for patients with regularly
      recurring fever episodes who failed to meet the classic Thomas criteria. We
      suggest that PFAPA syndrome should be suspected and tonsillectomy considered in
      children with a late onset of symptoms (>5 years of age) or when fever is the
      only symptom during the episodes.

PMID- 27692461
TI  - Epigenetic Regulation of the Thermogenic Adipose Program.
AB  - In contrast to white adipose tissue (WAT), which stores energy in the form of
      triglycerides, brown adipose tissue (BAT) dissipates energy by producing heat to
      maintain body temperature by burning glucose and fatty acids in a process called
      adaptive thermogenesis. The presence of an inducible thermogenic adipose tissue,
      and its beneficial effects for maintaining body weight and glucose and lipid
      homeostasis, has raised intense interest in understanding the regulation of
      thermogenesis. Elucidating the regulatory mechanisms underlying the thermogenic
      adipose program may provide excellent targets for therapeutics against obesity
      and diabetes. Here we review recent research on the role of epigenetics in the
      thermogenic gene program, focusing on DNA methylation and histone modifications.

PMID- 27692463
TI  - Variability in Management of First Cerebrospinal Fluid Shunt Infection: A
      Prospective Multi-Institutional Observational Cohort Study.
AB  - OBJECTIVES: To describe the variation in approaches to surgical and antibiotic
      treatment for first cerebrospinal fluid (CSF) shunt infection and adherence to
      Infectious Diseases Society of America (IDSA) guidelines. STUDY DESIGN: We
      conducted a prospective cohort study of children undergoing treatment for first
      CSF infection at 7 Hydrocephalus Clinical Research Network hospitals from April
      2008 through December 2012. Univariate analyses were performed to describe the
      study population. RESULTS: A total of 151 children underwent treatment for first
      CSF shunt-related infection. Most children had undergone initial CSF shunt
      placement before the age of 6 months (n =  98, 65%). Median time to infection
      after shunt surgery was 28 days (IQR 15-52 days). Surgical management was most
      often shunt removal with interim external ventricular drain placement, followed
      by new shunt insertion (n = 122, 81%). Median time from first negative CSF
      culture to final surgical procedure was 14 days (IQR 10-21 days). Median duration
      of intravenous (IV) antibiotic use duration was 19 days (IQR 12-28 days). For 84
      infections addressed by IDSA guidelines, 7 (8%) met guidelines and 61 (73%) had
      longer duration of IV antibiotic use than recommended. CONCLUSIONS: Surgical
      treatment for infection frequently adheres to IDSA guidelines of shunt removal
      with external ventricular drain placement followed by new shunt insertion.
      However, duration of IV antibiotic use in CSF shunt infection treatment was
      consistently longer than recommended by the 2004 IDSA guidelines.

PMID- 27692465
TI  - Response.

PMID- 27692466
TI  - Analytic cognitive style predicts paranormal explanations of anomalous
      experiences but not the experiences themselves: Implications for cognitive
      theories of delusions.
AB  - BACKGROUND AND OBJECTIVES: It has been proposed that delusional beliefs are
      attempts to explain anomalous experiences. Why, then, do anomalous experiences
      induce delusions in some people but not in others? One possibility is that people
      with delusions have reasoning biases that result in them failing to reject
      implausible candidate explanations for anomalous experiences. We examine this
      hypothesis by studying paranormal interpretations of anomalous experiences.
      METHODS: We examined whether analytic cognitive style (i.e. the willingness or
      disposition to critically evaluate outputs from intuitive processing and engage
      in effortful analytic processing) predicted anomalous experiences and paranormal
      explanations for these experiences after controlling for demographic variables
      and cognitive ability. RESULTS: Analytic cognitive style predicted paranormal
      explanations for anomalous experiences, but not the anomalous experiences
      themselves. LIMITATIONS: We did not study clinical delusions. Our attempts to
      control for cognitive ability may have been inadequate. Our sample was
      predominantly students. CONCLUSIONS: Limited analytic cognitive style might
      contribute to the interpretation of anomalous experiences in terms of delusional
      beliefs.

PMID- 27692468
TI  - Doing something about physician burnout.

PMID- 27692467
TI  - Regional variation in patient selection and treatment for lower extremity
      vascular disease in the Vascular Quality Initiative.
AB  - OBJECTIVE: Prior studies on the cause and effect of surgical variation have been
      limited by utilization of administrative data. The Vascular Quality Initiative
      (VQI), a robust national clinical registry, provides anatomic and perioperative
      details allowing a more robust analysis of variation in surgical practice.
      METHODS: The VQI was used to identify all patients undergoing infrainguinal open
      bypass or endovascular intervention from 2009 to 2014. Asymptomatic patients were
      excluded. The 16 regional groups of the VQI were used to compare variation in
      patient selection, operative indication, technical approach, and process
      measures. chi2 analysis was used to assess for differences across regions where
      appropriate. RESULTS: A total of 52,373 interventions were included (31%). Of the
      16,145 bypasses, 5% were performed for asymptomatic disease, 26% for
      claudication, 56% for chronic limb-threatening ischemia (CLI) (61% of these for
      tissue loss), and 13% for acute limb-threatening ischemia. Of the 35,338
      endovascular procedures, 4% were for asymptomatic disease, 40% for claudication,
      46% for CLI (73% tissue loss), and 12% for acute limb-threatening ischemia.
      Potentially unwarranted variation included proportion of prosthetic conduit for
      infrapopliteal bypass in claudication (13%-41%, median, 29%; P < .001), isolated
      tibial endovascular intervention for claudication (0.0%-5.0%, median, 3.0%; P <
      .001), discharge on antiplatelet and statin (bypass: 62%-84%; P < .001;
      endovascular: 63%-89%; P < .001), and ultrasound guidance for percutaneous access
      (claudication: range, 7%-60%; P < .001; CLI: 5%-65%; P < .001). Notable areas
      needing further research with significant variation include proportion of CLI vs
      claudication treated by bypass (38%-71%; P < .001) and endovascular intervention
      (28%-63%; P < .001), and use of closure devices in percutaneous access
      (claudication; 26%-76%; P < .001; CLI: 30%-78%; P < .001). CONCLUSIONS:
      Significant variation exists both in areas where evidence exists for best
      practice and, therefore, potentially unwarranted variation, and in areas of
      clinical ambiguity. Quality improvement efforts should be focused on reducing
      unwarranted variation. Further research should be directed at identifying best
      practice where no established guidelines and high variation exists.

PMID- 27692469
TI  - Interventions to prevent and reduce physician burnout: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Physician burnout has reached epidemic levels, as documented in
      national studies of both physicians in training and practising physicians. The
      consequences are negative effects on patient care, professionalism, physicians'
      own care and safety, and the viability of health-care systems. A more complete
      understanding than at present of the quality and outcomes of the literature on
      approaches to prevent and reduce burnout is necessary. METHODS: In this
      systematic review and meta-analysis, we searched MEDLINE, Embase, PsycINFO,
      Scopus, Web of Science, and the Education Resources Information Center from
      inception to Jan 15, 2016, for studies of interventions to prevent and reduce
      physician burnout, including single-arm pre-post comparison studies. We required
      studies to provide physician-specific burnout data using burnout measures with
      validity support from commonly accepted sources of evidence. We excluded studies
      of medical students and non-physician health-care providers. We considered
      potential eligibility of the abstracts and extracted data from eligible studies
      using a standardised form. Outcomes were changes in overall burnout, emotional
      exhaustion score (and high emotional exhaustion), and depersonalisation score
      (and high depersonalisation). We used random-effects models to calculate pooled
      mean difference estimates for changes in each outcome. FINDINGS: We identified
      2617 articles, of which 15 randomised trials including 716 physicians and 37
      cohort studies including 2914 physicians met inclusion criteria. Overall burnout
      decreased from 54% to 44% (difference 10% [95% CI 5-14]; p<0.0001; I2=15%; 14
      studies), emotional exhaustion score decreased from 23.82 points to 21.17 points
      (2.65 points [1.67-3.64]; p<0.0001; I2=82%; 40 studies), and depersonalisation
      score decreased from 9.05 to 8.41 (0.64 points [0.15-1.14]; p=0.01; I2=58%; 36
      studies). High emotional exhaustion decreased from 38% to 24% (14% [11-18];
      p<0.0001; I2=0%; 21 studies) and high depersonalisation decreased from 38% to 34%
      (4% [0-8]; p=0.04; I2=0%; 16 studies). INTERPRETATION: The literature indicates
      that both individual-focused and structural or organisational strategies can
      result in clinically meaningful reductions in burnout among physicians. Further
      research is needed to establish which interventions are most effective in
      specific populations, as well as how individual and organisational solutions
      might be combined to deliver even greater improvements in physician wellbeing
      than those achieved with individual solutions. FUNDING: Arnold P Gold Foundation
      Research Institute.

PMID- 27692470
TI  - Complement activation by cholesterol crystals triggers a subsequent cytokine
      response.
AB  - In the host a diverse collection of endogenous danger signals is constantly
      generated consisting of waste material as protein aggregates or crystalline
      materials that are recognized and handled by soluble pattern recognition
      receptors and phagocytic cells of the innate immune system. These signals may
      under certain circumstances drive processes leading to adverse inflammation. One
      example is cholesterol crystals (CC) that accumulate in the vessel wall during
      early phases of atherogenesis and represent an important endogenous danger signal
      promoting inflammation. CC is recognized by the lectin- and classical pathways of
      the complement system resulting in activation of C3 and C5 with release of
      inflammatory mediators like the potent C5a fragment. Complement activation by CC
      leads to crosstalk with the NLRP3 inflammasome-caspase-1 pathway and production
      of IL-1beta. Neutralization of IL-1beta may have beneficial effects on
      atherosclerosis and a large clinical trial with an IL-1beta inhibitor is
      currently in progress (the CANTOS study). However, upstream inhibition of CC
      induced inflammation by using a complement inhibitor may be more efficient in
      treating atherosclerosis since this will block initiation of inflammation
      processes before downstream release of cytokines including IL-1beta. Another
      therapeutic candidate can be broad-acting 2-hydroxypropyl-beta-cyclodextrin, a
      compound that targets several mechanisms such as cholesterol efflux, complement
      gene expression, and the NLRP3 pathway. In summary, emerging evidence show that
      complement is a key upstream player in the pathophysiology of atherosclerosis and
      that therapy aiming at inhibiting complement could be effective in controlling
      atherosclerosis.

PMID- 27692471
TI  - Seasonal exports and drivers of dissolved inorganic and organic carbon, carbon
      dioxide, methane and delta13C signatures in a subtropical river network.
AB  - Riverine systems act as important aquatic conduits for carbon transportation
      between atmospheric, terrestrial and oceanic pools, yet the magnitude of these
      exports remain poorly constrained. Interconnected creek and river sites (n=28)
      were sampled on a quarterly basis in three subcatchments of the subtropical
      Richmond River Catchment (Australia) to investigate spatial and temporal dynamics
      of dissolved inorganic carbon (DIC), dissolved organic carbon (DOC), carbon
      dioxide (CO2), methane (CH4), and carbon stable isotope ratios (delta13C). The
      study site is an area of high interest due to potential unconventional gas (coal
      seam gas or coal bed methane) development. DIC exports were driven by groundwater
      discharge with a small contribution by in situ DOC remineralization. The DIC
      exports showed seasonal differences ranging from 0.10 to 0.27mmolm-2catchmentd-1
      (annual average 0.17mmolm-2catchmentd-1) and peaked during winter when surface
      water discharge was highest. DOC exports (sourced from terrestrial organic
      matter) had an annual average 0.07mmolm-2catchmentd-1 and were 1 to 2 orders of
      magnitude higher during winter compared to spring and summer. CO2 evasion rates
      (annual average of 347mmolm-2water aread-1) were ~2.5 fold higher during winter
      compared to spring. Methane was always supersaturated (0.19 to 62.13MUM),
      resulting from groundwater discharge and stream-bed methanogenesis. Methane
      evasion was highly variable across the seasons with an annual average of
      3.05mmolm-2water aread-1. During drier conditions, stable isotopes implied
      enhanced CH4 oxidation. Overall, carbon losses from the catchment were dominated
      by CO2 evasion (60%) followed by DIC exports (30%), DOC exports (9%) and CH4
      evasion (<1%). Our results demonstrated broad catchment scale spatial and
      temporal variability in carbon dynamics, and that groundwater discharge and rain
      events controlled carbon exports.

PMID- 27692472
TI  - Application of the Multimedia Urban Model to estimate the emissions and
      environmental fate of PAHs in Tarragona County, Catalonia, Spain.
AB  - The Multimedia Urban Model (MUM-Fate) was used to estimate the emissions, fate
      and transport of polycyclic aromatic hydrocarbons (PAHs) in Tarragona County,
      Catalonia, Spain, where the largest chemical/petrochemical industrial complex of
      Southern Europe is located. MUM-Fate is a Level III steady-state fugacity model
      consisting of seven bulk media compartments (lower and upper air, surface water,
      sediment, soil, vegetation, and an organic film that coats impervious surfaces).
      The model was parameterized according to environmental conditions in Tarragona
      County, and used to back-calculate emissions from measured air concentrations of
      naphthalene, anthracene, phenanthrene, fluoranthene, pyrene, and benzo[a]pyrene.
      Modelled results in soils were within the range reported for measured
      concentrations. Estimated emissions of ?6PAH were 42ty-1, with phenanthrene
      having the greatest value (16ty-1). The fate and transport of ?6PAH were
      subsequently estimated by running the model an illustrative emission rate of
      1molh-1. Organic film on impervious surfaces was the compartment that achieved
      the highest concentrations of PAHs, being up to 2.108ngm-3. However, as the film
      conveys chemicals to surface waters, the persistence in this compartment was
      <1day. Soils and sediments were the greatest sinks for PAHs, with a persistence
      of 100-1000days. The greatest loss of PAHs was due to advection from air,
      followed by photodegradation from air. These results provide a first
      approximation of the current emissions and fate of PAHs in Tarragona County.

PMID- 27692473
TI  - Effect of combined spinal-epidural analgesia in labor on frequency of emergency
      cesarean delivery among nulliparous Chinese women.
AB  - OBJECTIVE: To determine whether combined spinal-epidural analgesia (CSEA) during
      labor increases the frequency of emergency cesarean delivery among Chinese
      nulliparous women. METHODS: In a retrospective study, the medical records of
      nulliparous women with a singleton fetus in cephalic presentation who delivered
      at term at Tongling Maternity Hospital, China, between January 2012 and December
      2014 were reviewed. Information about CSEA, mode of delivery, labor duration,
      oxytocin augmentation, and neonatal outcome was obtained. Logistic regression was
      used to examine independent associations between CSEA and emergency cesarean
      after controlling for confounding variables. RESULTS: Among 3456 women included,
      1786 (51.7%) received CSEA and 1670 (48.3%) received no labor analgesia.
      Emergency cesarean was more frequent among CSEA users (219/1786 [12.3%]) than non
      users (119/1670 [7.1%]; P<0.001). Among the maternal-fetal variables included in
      multivariate regression, maternal age, maternal height, cervical dilatation at
      admission, birth weight, and CSEA use were significantly associated with
      emergency cesarean. After adjustment, women with CSEA maintained a slightly
      increased risk for cesarean (adjusted odds ratio 1.54, 95% confidence interval
      1.20-2.00). CONCLUSION: Among Chinese nulliparous women, use of CSEA for labor
      pain was associated with an increased risk of emergency cesarean delivery;
      moreover, this effect was maintained after adjustment for other potential
      obstetric risk factors.

PMID- 27692474
TI  - Lateral-based Anterior Vaginal Wall Flap in the Treatment of Female Urethral
      Stricture: Efficacy and Safety.
AB  - BACKGROUND: Female urethral stricture is a rare condition. Different types of
      urethroplasty have been described. However, high quality studies are sparse. The
      most common technique used-the Blandy's technique-has resulted in our cases in a
      retrusive meatus and an inward urinary stream. OBJECTIVE: To show the efficacy
      and safety of an alternative vaginal wall flap urethroplasty. DESIGN, SETTING,
      AND PARTICIPANTS: A cross-sectional observational study was undertaken in a
      single University Hospital. Nine female patients previously diagnosed with
      urethral stricture at our institution underwent open surgery from 1993 to 2015.
      They were contacted and agreed to undergo a medical examination. SURGICAL
      PROCEDURE: A ventral lateral-based anterior vaginal wall flap urethroplasty
      inspired by the Orandi technique for male urethroplasty was performed.
      MEASUREMENTS: A chart review was performed. RESULTS AND LIMITATIONS: The mean age
      was 56 yr (41-78 yr). The mean follow-up was 80.7 mo (12-198). All patients had
      relief of symptoms. The meatus of all patients stayed in an orthotopic position
      without any impact on the direction of the urinary stream. The average caliber of
      the urethra increased from 10.8 Fr (6-18 Fr) to >=20 Fr. Peak flow improved from
      a mean of 6.8ml/s (3-11ml/s) to 21ml/s (14-35ml/s). No patient developed
      stricture recurrence or de novo stress urinary incontinence. There were no other
      immediate or delayed complications. All patients achieved a better score on the
      Patient Global Impression of Improvement questionnaire. CONCLUSIONS: Our study,
      with the same limitations that the few studies published in this field had, that
      is the few patients included, demonstrates that lateral anterior vaginal wall
      flap urethroplasty is an effective technique, offering durable results without
      apparent complications. PATIENT SUMMARY: We studied an alternative surgical
      technique for the treatment of female urethral stricture. We conclude that it is
      safe and effective with no apparent complications and good long-term results.

PMID- 27692475
TI  - Procedural training and assessment of competency utilizing simulation.
AB  - This review examines the current environment of neonatal procedural learning,
      describes an updated model of skills training, defines the role of simulation in
      assessing competency, and discusses potential future directions for simulation
      based competency assessment. In order to maximize impact, simulation-based
      procedural training programs should follow a standardized and evidence-based
      approach to designing and evaluating educational activities. Simulation can be
      used to facilitate the evaluation of competency, but must incorporate validated
      assessment tools to ensure quality and consistency. True competency evaluation
      cannot be accomplished with simulation alone: competency assessment must also
      include evaluations of procedural skill during actual clinical care. Future work
      in this area is needed to measure and track clinically meaningful patient
      outcomes resulting from simulation-based training, examine the use of simulation
      to assist physicians undergoing re-entry to practice, and to examine the use of
      procedural skills simulation as part of a maintenance of competency and life-long
      learning.

PMID- 27692476
TI  - Neonatal outreach simulation.
AB  - Numerous factors contribute to neonatal morbidity and mortality, and
      inexperienced providers managing crisis situations is one major cause. Simulation
      based medical education is an excellent modality to employ in community hospitals
      to help refine and refresh resuscitation skills of providers who infrequently
      encounter neonatal emergencies. Mounting evidence suggests that simulation-based
      education improves patient outcomes. Academic health centers have the potential
      to improve neonatal outcomes through collaborations with community hospital
      providers, sharing expertise in neonatal resuscitation and simulation. Community
      outreach programs using simulation have been successfully initiated in North
      America. Two examples of programs are described here, including the models for
      curricular development, required resources, limitations, and benefits.
      Considerations for initiating outreach simulation programs are discussed. In the
      future, research demonstrating improved neonatal outcomes using outreach
      simulation will be important for personnel conducting outreach programs. Neonatal
      outreach simulation is a promising educational endeavor that may ultimately prove
      important in decreasing neonatal morbidity and mortality.

PMID- 27692477
TI  - NICE guidance on necitumumab for untreated advanced or metastatic squamous non
      small-cell lung cancer.

PMID- 27692478
TI  - NICE guidance for talimogene laherparepvec for unresectable metastatic melanoma.

PMID- 27692479
TI  - The fight against rabies: the Middle East needs to step up its game.

PMID- 27692480
TI  - Research Priorities from Animal Behaviour for Maximising Conservation Progress.
AB  - Poor communication between academic researchers and wildlife managers limits
      conservation progress and innovation. As a result, input from overlapping fields,
      such as animal behaviour, is underused in conservation management despite its
      demonstrated utility as a conservation tool and countless papers advocating its
      use. Communication and collaboration across these two disciplines are unlikely to
      improve without clearly identified management needs and demonstrable impacts of
      behavioural-based conservation management. To facilitate this process, a team of
      wildlife managers and animal behaviour researchers conducted a research
      prioritisation exercise, identifying 50 key questions that have great potential
      to resolve critical conservation and management problems. The resulting agenda
      highlights the diversity and extent of advances that both fields could achieve
      through collaboration.

PMID- 27692481
TI  - Detecting the Multiple Facets of Biodiversity: (Trends in Ecology & Evolution 31,
      527-538, July 2016).

PMID- 27692482
TI  - Corrigendum to "Identity and intimacy during adolescence: Connections among
      identity styles, romantic attachment and identity commitment" [J. Adolesc. 35
      (2012) 1427-1439].

PMID- 27692483
TI  - Corrigendum to "Placental (pro)renin receptor expression and plasma soluble
      (pro)renin receptor levels in preeclampsia" [YPLAC 37C (2016) 72-78].

PMID- 27692484
TI  - Comparison of ultrasound and fluoroscopic guidance for injection in CT
      arthrography and MR arthrography of the hip.
AB  - OBJECTIVE: To evaluate the usefulness of ultrasound-guided versus fluoroscopy
      guided injection in CT arthrography and MR arthrography. MATERIAL AND METHODS: We
      reviewed all CT arthrography and MR arthrography studies done at our center
      between October 1, 2014 and October 1, 2015. We analyzed 32 studies: 26 with
      fluoroscopic guidance and 6 with ultrasound guidance. We compared the two
      techniques on the following parameters: presence of sufficient contrast material
      in the joint, extravasation or injection of contrast material in the soft tissues
      (presence of contrast material in the psoas or other soft tissues), and intra
      articular gas bubbles. We used SPSS V. 20 to compare the techniques with
      Pearson's chi-square tests. RESULTS: Contrast material was observed in soft
      tissues in 56.3% of ultrasound-guided injections, making 6.3% of the procedures
      invalid for diagnostic purposes. Extravasation of contrast material was observed
      in 53.8% of fluoroscopy-guided procedures, making 3.8% invalid for diagnostic
      purposes. Intra-articular gas was observed in 21.9% of ultrasound-guided studies
      and in 38.5% of fluoroscopy-guided studies. None of the differences between
      techniques were statistically significant at p<0.05. CONCLUSIONS: Our study shows
      that ultrasound is as useful as fluoroscopy for injecting contrast material for
      CT arthroscopy and MR arthroscopy; ultrasound has the advantage of not using
      ionizing radiation.

PMID- 27692485
TI  - Determination of the concentrations of alternative antifouling agents on the
      Korean coast.
AB  - Since the ban on tributyltin (TBT) in 2008, dozens of alternative antifouling
      agents have been used instead. Unfortunately, these alternative antifouling
      agents contain diverse toxic components, which have contaminated the coasts. From
      2006 to 2013, the concentration of chlorothalonil, dichlofluanid, and Irgarol
      1051 were monitored continuously, and their mean concentrations increased due to
      the increase in maritime cargo and consequent increase in the incoming and
      outgoing ships in harbors. An analysis of the sampling points according to harbor
      type showed that the contamination was more severe in fishing and big harbors,
      where there are more incoming and outgoing ships. A correlation analysis
      indicated a high correlation between chlorothalonil and dichlofluanid. Unlike
      Irgarol 1051, which is only used as an antifouling agent, the other two
      substances are used as agricultural chemicals as well, which could explain the
      high correlation. This study suggests that these alternative antifouling agents
      should be tracked continuously.

PMID- 27692486
TI  - Excess seawater nutrients, enlarged algal symbiont densities and bleaching
      sensitive reef locations: 2. A regional-scale predictive model for the Great
      Barrier Reef, Australia.
AB  - A spatial risk assessment model is developed for the Great Barrier Reef (GBR,
      Australia) that helps identify reef locations at higher or lower risk of coral
      bleaching in summer heat-wave conditions. The model confirms the considerable
      benefit of discriminating nutrient-enriched areas that contain corals with
      enlarged (suboptimal) symbiont densities for the purpose of identifying bleaching
      sensitive reef locations. The benefit of the new system-level understanding is
      showcased in terms of: (i) improving early-warning forecasts of summer bleaching
      risk, (ii) explaining historical bleaching patterns, (iii) testing the bleaching
      resistant quality of the current marine protected area (MPA) network (iv)
      identifying routinely monitored coral health attributes, such as the tissue
      energy reserves and skeletal growth characteristics (viz. density and extension
      rates) that correlate with bleaching resistant reef locations, and (v) targeting
      region-specific water quality improvement strategies that may increase reef-scale
      coral health and bleaching resistance.

PMID- 27692487
TI  - The ITS-based phylogeny of fungi associated with tarballs.
AB  - Tarballs, the remnants of crude oil which change into semi-solid phase due to
      various weathering processes in the sea, are rich in hydrocarbons, including
      toxic and almost non-degradable hydrocarbons. Certain microorganisms such as
      fungi are known to utilize hydrocarbons present in tarballs as sole source of
      carbon for nutrition. Previous studies have reported 53 fungal taxa associated
      with tarballs. There is apparently no gene sequence-data available for the
      published taxa so as to verify the fungal identification using modern taxonomic
      tools. The objective of the present study is to isolate fungi from tarballs
      collected from Candolim beach in Goa, India and investigate their phylogenetic
      diversity based on 5.8S rRNA gene and the flanking internal transcribed spacer
      regions (ITS) sequence analysis. In the ITS-based NJ tree, eight tarball
      associated fungal isolates clustered with 3 clades of Dothideomycetes and 2
      clades of Saccharomycetes. To the best of our knowledge, this is the first study
      that has employed ITS-based phylogeny to characterize the fungal diversity
      associated with tarballs. Further studies are warranted to investigate the role
      of the tarball-associated fungi in degradation of recalcitrant hydrocarbons
      present in tarballs and the role of tarballs as carriers of human pathogenic
      fungi.

PMID- 27692488
TI  - Large microplastic particles in sediments of tributaries of the River Thames, UK 
      Abundance, sources and methods for effective quantification.
AB  - : Sewage effluent input and population were chosen as predictors of microplastic
      presence in sediments at four sites in the River Thames basin (UK). Large
      microplastic particles (1mm-4mm) were extracted using a stepwise approach to
      include visual extraction, flotation and identification using Raman spectroscopy.
      Microplastics were found at all four sites. One site had significantly higher
      numbers of microplastics than other sites, average 66 particles 100g-1, 91% of
      which were fragments. This site was downstream of a storm drain outfall receiving
      urban runoff; many of the fragments at this site were determined to be derived of
      thermoplastic road-surface marking paints. At the remaining three sites, fibres
      were the dominant particle type. The most common polymers identified included
      polypropylene, polyester and polyarylsulphone. This study describes two major new
      findings: presence of microplastic particles in a UK freshwater system and
      identification of road marking paints as a source of microplastics. CAPSULE: This
      study is the first to quantify microplastics of any size in river sediments in
      the UK and links their presence to terrestrial sources including sewage and road
      marking paints.

PMID- 27692489
TI  - History and the future: Looking back to look forward?
AB  - History is often dismissed as of little utility in the analysis of policy. This
      paper provides a justification for its use as evidence. It surveys the rise of
      the use of history, including public history and history and policy. It looks at
      two issues which draw on the author's own work: the relationship between
      regulation and culture for smoking and alcohol; and the response to electronic
      cigarettes in the light of smoking and public health history. It analyses what
      history can contribute. Responses are time dependent and change is an essential
      parameter in understanding policy. Historical research can challenge stereotypes,
      for example that prohibition was abandoned because it 'failed'. It also forms the
      bedrock of historical interpretation, which is mutable and often misunderstood
      outside the profession. History provides policy analysis rather than policy
      prescription and is a challenging approach, not just a convenient support for
      established positions. The paper concludes that history is far from moribund as a
      policy science.

PMID- 27692492
TI  - Older persons' expressions of emotional cues and concerns during home care
      visits. Application of the Verona coding definitions of emotional sequences (VR
      CoDES) in home care.
AB  - OBJECTIVE: This study aims to a) explore to what extent older persons express
      emotional cues and concerns during home care visits; b) describe what cues and
      concerns these older persons expressed, and c) explore who initiated these cues
      and concerns. METHODS: A descriptive and cross-sectional study was conducted.
      Data consisted of 188 audio recorded home care visits with older persons and
      registered nurses or nurse assistants, coded with the Verona coding definitions
      on emotional sequences (VR-CoDES). RESULTS: Emotional expressions of cues and
      concerns occurred in 95 (51%) of the 188 recorded home care visits. Most frequent
      were implicit expressions of cues (n=292) rather than explicit concerns (n=24).
      Utterances with hints to hidden concerns (63,9%, n=202) were most prevalent,
      followed by vague or unspecific expressions of emotional worries (15,8%, n=50).
      Most of these were elicited by the nursing staff (63%, n=200). CONCLUSION:
      Emotional needs expressed by the older persons receiving home care were mainly
      communicated implicitly. To be attentive to such vaguely expressed emotions may
      demand nursing staff to be sensitive and open. PRACTICE IMPLICATIONS: The VR
      CoDES can be applied on audio recorded home care visits to analyse verbal and
      emotional communication, and may allow comparative research.

PMID- 27692491
TI  - Patient and family communication during consultation visits: The effects of a
      decision aid for treatment decision-making for localized prostate cancer.
AB  - OBJECTIVE: To analyze the effects of a decision aid on improving patients' and
      family members' information giving and question asking during consultations for
      prostate cancer treatment decision-making. METHODS: This study is a secondary
      analysis of archived audio-recorded real-time consultation visits with
      participants from a randomized clinical trial. Participants were randomly
      assigned into three groups: TD-intervention targeted patient-only; TS
      intervention targeted patients and family members; and control-a handout on
      staying healthy during treatment. We conducted content analysis using a
      researcher-developed communication coding system. Using SAS 9.3, we conducted Chi
      square/Fisher's exact test to examine whether information giving and question
      asking among patients and family members varied by groups when discussing
      different content/topics. RESULTS: Compared with those in the TS and control
      groups, significantly higher percentages of participants in the TD group
      demonstrated information giving in discussing topics about diagnosis, treatment
      options, risks and benefits, and preferences; and engaged in question asking when
      discussing diagnosis, watchful waiting/active surveillance, risks and benefits,
      and preferences for treatment impacts. CONCLUSION: Information support and
      communication skills training for patients were effective in improving
      communication during treatment decision-making consultations. PRACTICE
      IMPLICATIONS: Providing information about prostate cancer and communication
      skills training empower patients and their family members.

PMID- 27692493
TI  - Testing whether barriers to a hypothetical screening test affect unrelated
      perceived benefits and vice versa: A randomised, experimental study.
AB  - OBJECTIVE: Determine whether (fictitious) health screening test benefits affect
      perceptions of (unrelated) barriers, and barriers affect perceptions of benefits.
      METHODS: UK adults were recruited via an online survey panel and randomised to
      receive a vignette describing a hypothetical screening test with either high or
      low benefits (higher vs. lower mortality reduction) and high or low barriers
      (severe vs. mild side-effects; a 2*2 factorial design). ANOVAs compared mean
      perceived benefits and barriers scores. Screening 'intentions' were compared
      using Pearson's chi2 test. RESULTS: Benefits were rated less favourably when
      barriers were high (mean: 27.4, standard deviation: 5.3) than when they were low
      (M: 28.5, SD: 4.8; p=0.010, partial eta2=0.031). Barriers were rated more
      negatively when benefits were low (M: 17.1, SD: 7.6) than when they were high (M:
      15.7, SD: 7.3; p=0.023, partial eta2=0.024). Most intended to have the test in
      all conditions (73-81%); except for the low benefit-high barrier condition (37%;
      p<0.0005; N=218). CONCLUSIONS: Perceptions of test attributes may be influenced
      by unrelated characteristics. PRACTICE IMPLICATIONS: Reducing screening test
      barriers alone may have suboptimal effects on perceptions of barriers if benefits
      remain low; increasing screening benefits may not improve perceptions of benefits
      if barriers remain high.

PMID- 27692494
TI  - Personal trainers are confident in their ability to provide nutrition care: a
      cross-sectional investigation.
AB  - OBJECTIVE: To measure the self-perceived competence of Australian personal
      trainers in providing nutrition care. STUDY DESIGN: Cross-sectional online
      survey. METHODS: A validated survey was used to measure confidence in the ability
      to provide nutrition care among a snowball sample of 142 Australian-based
      personal trainers. The survey used 5-point Likert scale statements across four
      nutrition related constructs: knowledge; skills; communication and counselling;
      and attitudes. Scores for each construct were averaged and summed to provide a
      self-reported nutrition competence score as a percentage. Pearson Chi-squared
      analyses were used to identify associations between demographic variables and
      competence scores, and associations between construct scores. RESULTS: Personal
      trainers felt confident to provide nutrition care for all clients (mean score
      76%; 'very confident'). Greater confidence in nutrition knowledge was seen in
      personal trainers with greater experience (chi2 = 6.946, P = 0.008) and education
      higher than a certificate IV (chi2 = 5.079, P = 0.024). Greater confidence in
      nutrition knowledge was also associated with greater confidence in nutrition
      skills (chi2 = 49.67, P <= 0.001) and more favourable attitudes towards providing
      nutrition care (chi2 = 4.73, P = 0.03). CONCLUSIONS: Personal trainers feel
      confident in their ability and show favourable attitudes towards providing
      nutrition care to clients. This workforce has the potential to support lifestyle
      modification for chronic disease prevention.

PMID- 27692495
TI  - Understanding brain development: a major step.

PMID- 27692496
TI  - Clinicopathologic factors associated with de novo metastatic breast cancer.
AB  - While breast cancers with distant metastasis at presentation (de novo metastasis)
      harbor significantly inferior clinical outcomes, there have been limited studies
      analyzing the clinicopathologic characteristics in this subset of patients. In
      this study, we analyzed 6126 breast cancers diagnosed between 1998 and 2013 to
      identify factors associated with de novo metastatic breast cancer. When compared
      to patients without metastasis at presentation, race, histologic grade,
      estrogen/progesterone receptor (ER/PR) and HER2 statuses were significantly
      associated with de novo metastasis in the entire cohort, whereas age, histologic
      grade, PR and HER2 status were the significant parameters in the subset of
      patients with locally advanced breast cancer (Stage IIB/III). The patients with
      de novo metastatic breast cancer had a significant older mean age and a lower
      proportion of HER2-positive tumors when compared to those with metastatic
      recurrence. Further, the HER2-rich subtype demonstrated a drastically higher
      incidence of de novo metastasis when compared to the luminal and triple-negative
      breast cancers in the entire cohort [odds ratio (OR)=5.68 and 2.27, respectively]
      and in the patients with locally advanced disease (OR=4.02 and 2.12,
      respectively), whereas no significant difference was seen between de novo
      metastatic cancers and those with metastatic recurrence. Moreover, the luminal
      and HER2-rich subtypes showed bone-seeking (OR=1.92) and liver-homing (OR=2.99)
      characteristics, respectively, for the sites of de novo metastasis, while the
      latter was not observed in those with metastatic recurrence. Our data suggest
      that an algorithm incorporating clinicopathologic factors, especially histologic
      grade and receptor profile, remains of significant benefit during decision making
      in newly diagnosed breast cancer in the pursuit of precision medicine.

PMID- 27692497
TI  - Can dressings soaked with polyhexanide reduce bacterial loads in full-thickness
      skin grafting? A randomized controlled trial.
AB  - BACKGROUND: Polyhexamethylene biguanide (PHMB)-based antiseptic solutions can
      reduce bacterial loads in different clinical settings and are believed to lower
      risk of infections. OBJECTIVE: We sought to assess the efficacy of a PHMB-based
      solution in lowering bacterial loads of full-thickness skin grafting wounds and
      the risk of surgical site infections (SSIs). METHODS: In this double-blinded
      clinical trial, 40 patients planned for facial full-thickness skin grafting were
      randomized 1:1 to receive tie-over dressings soaked with either PHMB-based
      solution or sterile water. Quantitative and qualitative bacterial analysis was
      performed on all wounds before surgery, at the end of surgery, and 7 days
      postoperatively. In addition, all patients were screened for nasal colonization
      of Staphylococcus aureus. RESULTS: Analysis of wounds showed no statistically
      significant difference in bacterial reductions between the groups. The SSI rates
      were significantly higher in the intervention group (8/20) than in the control
      group (2/20) (P = .028). Higher postoperative bacterial loads were a common
      finding in SSIs (P = .011). This was more frequent when S aureus was present
      postoperatively (P = .034), intraoperatively (P = .03), and in patients with
      intranasal S aureus colonization (P = .007). LIMITATIONS: Assessment of SSIs is
      largely subjective. In addition, this was a single-center study and the total
      number of participants was 40. CONCLUSION: Soaking tie-over dressings with PHMB
      solution in full-thickness skin grafting had no effect on postoperative bacterial
      loads and increased the risk of SSI development. The presence of S aureus
      intranasally and in wounds preoperatively and postoperatively increased
      postoperative bacterial loads, which in turn resulted in significantly more SSIs.

PMID- 27692499
TI  - Fertilization success of sterlet Acipenser ruthenus and Siberian sturgeon
      Acipenser baerii gametes under conditions of heterospecific mating.
AB  - Species may be prevented from interspecific hybridization by a number of
      different reproductive barriers that operate precopulatory and postcopulatory. In
      situation, when natural precopulatory reproductive barriers are affected by
      anthropogenic factors, postcopulatory reproductive barriers may be important for
      maintaining gametic isolation and hence preventing interspecific hybridization.
      This is highly topical in sturgeon (order Acipenseriformes) which exhibits
      remarkable ease of interspecific hybridization. The objectives of the present
      study were to evaluate the fertilization success of Acipenser ruthenus and
      Acipenser baerii spermatozoa under the interspecific competitive conditions and
      assessed, whether their spermatozoa tend to differentially fertilize eggs of
      conspecifics. We set up several in vitro fertilization experiments: (i) pooled
      eggs of both species were fertilized by sperm of each species separately; (ii)
      eggs of each species were fertilized by pooled sperm; (iii) pooled eggs were
      fertilized by pooled sperm and (iv) purebred and hybrid control groups. Using
      parental assignment by molecular markers, we found that when these species
      competed in pooled sperm, 78.9% of progeny were sired by A. ruthenus and 21.1% by
      A. baerii, demonstrating higher fertilization success for the former,
      irrespective of conspecificity of fertilized eggs. When pooled eggs were
      inseminated by A. ruthenus or A. baerii sperm separately, progeny almost equally
      comprised hybrid and purebred individuals. Hence, neither A. ruthenus nor A.
      baerii eggs showed a tendency to biased fertilization by spermatozoa of
      conspecific males. These findings together show that there may not be
      postcopulatory mechanisms preventing hybridization between A. ruthenus and A.
      baerii.

PMID- 27692498
TI  - Impact of ixekizumab on psoriasis itch severity and other psoriasis symptoms:
      Results from 3 phase III psoriasis clinical trials.
AB  - BACKGROUND: Itch is a prevalent symptom of psoriasis that impacts quality of
      life. OBJECTIVE: We sought to describe improvements in itch severity, skin pain,
      and bothersomeness of skin appearance caused by psoriasis among patients who
      received ixekizumab, etanercept, or placebo in three 12-week, phase III clinical
      trials (UNCOVER-1, -2, and -3). METHODS: The itch numeric rating scale evaluated
      psoriasis itch severity in all 3 trials. Skin pain was assessed by skin pain
      visual analog scale. Bothersomeness because of redness/discoloration, thickness,
      and scaling/flaking was assessed with the Psoriasis Skin Appearance
      Bothersomeness instrument. Psoriasis skin appearance bothersomeness and skin pain
      were assessed at baseline and week 12; itch numeric rating scale score was
      assessed at baseline and weeks 1, 2, 4, 8, and 12. RESULTS: Patients who received
      ixekizumab demonstrated statistically significant improvements (P < .001) in itch
      severity, reduction in skin pain, and degree of bothersomeness compared with
      those who received etanercept or placebo. Clinically meaningful improvements in
      itch severity were achieved as early as week 1. LIMITATIONS: Longer-term
      evaluations of psoriasis symptom improvement with ixekizumab treatment are
      needed. CONCLUSION: After treatment with ixekizumab, patients reported fast,
      significant, and clinically meaningful improvements in itch severity and other
      psoriasis-related symptoms such as skin pain and skin appearance bothersomeness.

PMID- 27692500
TI  - One-year metreleptin therapy decreases PCSK9 serum levels in diabetic patients
      with monogenic lipodystrophy syndromes.

PMID- 27692501
TI  - Sexual chemoecology of mosquitoes (Diptera, Culicidae): Current knowledge and
      implications for vector control programs.
AB  - Mosquitoes (Diptera: Culicidae) act as vectors of medical and veterinary
      importance, due to their ability to transmit many pathogens and parasites.
      Renewed interest has been recently devoted to the potential of sterile insect
      technique (SIT) for mosquito suppression. However, the success of the SIT is
      mostly dependent on the ability of sterile males to compete for mates with the
      wild ones in the field. Nevertheless, little is known on the sexual chemical
      ecology of mosquitoes, with special reference to the role of chemical signals in
      males. We reviewed the current knowledge on mosquito sexual chemical ecology and
      other key cues affecting courtship and mating behavior. The information available
      on the aggregation and sex pheromones in mosquito males is rather limited. To the
      best of our knowledge, the components of the aggregation pheromone stimulating
      swarming mechanisms have been fully characterized only for Aedes aegypti, while
      evidence for aggregation pheromones in other mosquito species remains elusive.
      Further research on this issue is needed, as well as to dissect the relative
      importance of visual (with special reference to swarming landmarks), vibrational,
      olfactory and tactile cues perceived during swarming and mate. On the other hand,
      more knowledge is available for cuticular hydrocarbons, which modulate mating
      behavior in several species of economic importance. These compounds, coupled with
      volatile aggregation components, have potential interest for the development of
      monitoring and trapping systems. In addition, the analyses of cuticular
      hydrocarbons are essential for discrimination between closely related mosquito
      species and/or populations.

PMID- 27692502
TI  - Intraoperative rupture in the surgical treatment of patients with intracranial
      aneurysms.
AB  - Intraoperative rerupture (IOR) during clipping of cerebral aneurysms is a
      difficult complication of microneurosurgery. The aim of this study was to
      evaluate the incidence of IOR and analyze the strategies for controlling profound
      hemorrhage. A total of 165 patients with unruptured intracranial aneurysms and 46
      patients with subarachnoid hemorrhage (SAH) treated surgically between April 2010
      and March 2011, were reviewed. The data were collected with regard to age, sex,
      presence of symptoms, confounding factors and strategy for controlling
      intraoperative hemorrhage was analyzed in terms of location of aneurysms, timing
      of rupture and severity of IOR. 211 patients with 228 aneurysms were treated in
      this series. There were a total of six IORs which represented an IOR rate of
      2.84% per patient and 2.63% per aneurysm. The highest ruptures rates occurred in
      patients with internal carotid artery aneurysms (25%). Surgeries in the group
      with ruptured aneurysms had a much higher rate of IOR compared with surgeries in
      the group with unruptured aneurysms. Of the six IOR aneurysms, one occurred
      during predissection, four during microdissection and one during clipping. One
      was major IOR, three were moderate and two were minor. Intraoperative rupture of
      an intracranial aneurysm can be potentially devastating in vascular neurosurgery.
      Aneurysm location, presence of SAH and surgical experience of the operating
      surgeon seem to be important factors affecting the incidence of IOR.

PMID- 27692503
TI  - A 14-year-old boy with extranodal natural killer cell lymphoma of the nose,
      nasopharynx, larynx, and trachea in remission 6years after primary diagnosis. A
      longitudinal case report.
AB  - Nasal type extranodal natural killer/T-cell lymphoma (ENKTL) is a rare lymphoma
      in the USA and Europe but endemic in East Asia and in areas of South and Central
      America. Clinically natural killer cell lymphomas are divided into three
      categories; nasal, non-nasal and aggressive lymphoma/leukemia subtypes. ENKTL,
      nasal type occurs in the nose and can extend to the upper aero-digestive tract as
      reported in this longitudinal case study. This is a longitudinal report of
      progress of a 14-year-old boy with ENKTL originating in the nasal cavity with
      subsequent extension and recurrence in the contralateral nose, nasopharynx,
      larynx and trachea presenting with varying degrees of respiratory problems and
      eventually, respiratory distress. Caregiver refusal of stem cell transplantation
      prompted an alternative diagnostic and therapeutic approach. Clinical course with
      recurrences, extensions and remissions over 6years with tailored endoscopic
      surgical treatment and radiochemotherapy is documented to present a guide in the
      multidisciplinary management of this rare disease.

PMID- 27692504
TI  - Association of Healthy Home Environments and Use of Patient-Centered Medical
      Homes by Children of Low-Income Families.
AB  - INTRODUCTION: Medicaid agencies have been promoting the patient-centered medical
      home (PCMH) model. Most caregivers choose physician practices for their children,
      and we hypothesized that those following healthier childrearing practices are
      more likely to seek care in a PCMH. METHOD: We selected children with public
      insurance plans (n = 20,801) from the 2011-2012 National Survey of Children's
      Health. We used generalized ordinal logistic regression with state fixed effects
      to assess the association between home environments and children's use of PCMHs.
      RESULTS: Children living in the healthiest homes were 1.33 times (p = .001) more
      likely to receive care from the highest level of PCMH. In states with early PCMH
      implementation, the odds increased to 2.11 times (p = .001). DISCUSSION: Our
      results show a significant, sizeable relationship between healthier home
      environments and the use of PCMH by children from low-income families. They
      provide implications for assessing the effect of PCMH use on health outcomes and
      use patterns.

PMID- 27692505
TI  - Reflections on Incorporating a Behavioral Intervention into a Busy Pediatric
      Subspecialty Clinic.

PMID- 27692506
TI  - Development of the 24/7 Nurse Practitioner Model on the Inpatient Pediatric
      General Surgery Service at a Large Tertiary Care Children's Hospital and
      Associated Outcomes.
AB  - Nurse practitioners (NPs) have been providing high-quality and safe patient care
      for a few decades, and evidence showing the extent of their impact is emerging.
      This article describes the implementation of a 24/7 NP patient care model on an
      inpatient pediatric general surgery service in a tertiary free-standing
      Children's Hospital in the Northeastern United States. The literature shows that
      there is limited evidence regarding NP models of care and their effect on patient
      outcomes. In response to policy changes leading to reduction of resident work
      hours and a more acute and complex inpatient pediatric general surgery patient
      population, our existing NP model evolved into a 24/7 NP Model in June 2011. The
      results from two quality improvement projects showed positive registered nurse
      and attending surgeon staff satisfaction with the 24/7 NP Model of care and a
      decreased trend of unplanned intensive care unit patient transfers after the 24/7
      NP Model implementation. These findings further support the evidence in the
      literature that NPs provide safe and quality patient care.

PMID- 27692507
TI  - Environmental Tobacco Smoke: Public Perception of Risks of Exposing Children to
      Second- and Third-Hand Tobacco Smoke.
AB  - INTRODUCTION: Extensive evidence exists regarding health risks posed by
      children's exposure to second-hand smoke, and there is increasing evidence
      concerning the risks of third-hand smoke. This evidence is most meaningful if the
      public is aware of these risks and can help curb childhood exposure. METHODS:
      Participants were selected at an academic medical center and asked to complete a
      survey. Responses were compared based on respondents' smoking status and the
      presence or absence of children in their homes. RESULTS: A total of 310 adults
      responded. Nonsmokers and respondents living with children were more likely to
      see smoking in the home as affecting all the queried health problems (p < .05).
      Knowledge of the risks of second-hand smoke exposure is limited, and very few
      respondents perceived risk from third-hand smoke exposure. DISCUSSION: The
      widespread lack of awareness of the risks associated with environmental tobacco
      smoke must be addressed to curb childhood exposure.

PMID- 27692508
TI  - Fractional flow reserve in France: Free access at last?

PMID- 27692509
TI  - Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused
      3-ring system based on the 'reversed' amide scaffold.
AB  - The Wnt signaling pathway is an essential signal transduction pathway which leads
      to the regulation of cellular processes such as proliferation, differentiation
      and migration. Aberrant Wnt signaling is known to have an association with
      multiple cancers. Porcupine is an enzyme that catalyses the addition of
      palmitoleate to a serine residue in Wnt proteins, a process which is required for
      the secretion of Wnt proteins. Here we report the synthesis and structure
      activity-relationship of the novel porcupine inhibitors based on a 'reversed'
      amide scaffold. The leading compound 53 was as potent as the clinical compound
      LGK974 in a cell based STF reporter gene assay. Compound 53 potently inhibited
      the secretion of Wnt3A, therefore was confirmed to be a porcupine inhibitor.
      Furthermore, compound 53 showed excellent chemical and plasma stabilities.
      However, the clearance of compound 53 in liver microsomal tests was moderate to
      high, and the solubility of compound 53 was suboptimal. Collective efforts toward
      further optimization of this novel tricyclic template to develop better porcupine
      inhibitors will be subsequently undertaken and reported in due course.

PMID- 27692510
TI  - Synthesis and Pin1 inhibitory activity of thiazole derivatives.
AB  - Pin1 (Protein interacting with NIMA1) is a peptidyl prolyl cis-trans isomerase
      (PPIase) which specifically catalyze the conformational conversion of the amide
      bond of pSer/Thr-Pro motifs in its substrate proteins and is a novel promising
      anticancer target. A series of new thiazole derivatives were designed and
      synthesized, and their inhibitory activities were measured against human Pin1
      using a protease-coupled enzyme assay. Of all the tested compounds, a number of
      thiazole derivatives bearing an oxalic acid group at 4-position were found to be
      potent Pin1 inhibitors with IC50 values at low micromolar level. The detailed
      structure-activity relationships were analyzed and the binding features of
      compound 10b (IC50 5.38MUM) was predicted using CDOCKER program. The results of
      this research would provide informative guidance for further optimizing thiazole
      derivatives as potent Pin1 inhibitors.

PMID- 27692511
TI  - Life cycle assessment of carbon capture and utilization from ammonia process in
      Mexico.
AB  - Post-combustion CO2 capture (PCC) of flue gas from an ammonia plant (AP) and the
      environmental performance of the carbon capture utilization (CCU) technology for
      greenhouse gas (GHG) emissions to an enhanced oil recovery (EOR) system in Mexico
      was performed as case study. The process simulations (PS) and life cycle
      assessment (LCA) were used as supporting tools to quantify the CO2 capture and
      their environmental impacts, respectively. Two scenarios were considered: 1) the
      AP with its shift and CO2 removal unit and 2) Scenario 1 plus PCC of the flue gas
      from the AP primary reformer (AP-2CO2) and the global warming (GW) impact. Also,
      the GW of the whole of a CO2-EOR project, from these two streams of captured CO2,
      was evaluated. Results show that 372,426 tCO2/year can be PCC from the flue gas
      of the primary reformer and 480,000 tons/y of capacity from the AP. The energy
      requirement for solvent regeneration is estimated to be 2.8 MJ/kgCO2 or a GW
      impact of 0.22 kgCO2e/kgCO2 captured. GW performances are 297.6 kgCO2e
      emitted/barrel (bbl) for scenario one, and 106.5 kgCO2e emitted/bbl for the
      second. The net emissions, in scenario one, were 0.52 tCO2e/bbl and 0.33
      tCO2e/bbl in scenario two. Based on PS, this study could be used to evaluate the
      potential of CO2 capture of 4080 t/d of 4 ammonia plants. The integration of PS
      LCA to a PCC study allows the applicability as methodological framework for the
      development of a cluster of projects in which of CO2 could be recycled back to
      fuel, chemical, petrochemical products or for enhanced oil recovery (EOR). With
      AP-2CO2, "CO2 emission free" ammonia production could be achieved.

PMID- 27692512
TI  - Fourier transform infra-red (FTIR) spectroscopy investigation, dose effect,
      kinetics and adsorption capacity of phosphate from aqueous solution onto laterite
      and sandstone.
AB  - Environmental pollution by phosphate in developing countries is growing with
      extensive and diffuse pollution. Solving these problem with intensive
      technologies is very expensive. Using natural sorbent such as laterite and
      sandstone could be a solution. The main objective of the study is to evaluate the
      P-removal efficiency of these materials under various solution properties.
      Laterite and sandstone used mainly contain very high levels of finely grained
      iron and aluminum oxy-hydroxides and diverse dioctahedral clays. Phosphate
      adsorption tests were carried out using crushed laterite and sandstone. Optimal
      doses and pH effects on phosphate adsorption were studied with a potassium
      hydrogeno-phosphate solution of 5 mg/L at 30  degrees C. The main results were
      that the optimal dosage is 15 and 20 mg/L respectively for laterite and
      sandstone. The phosphate adsorptions efficiency of laterite and sandstone are pH
      dependent, they increase when the pH grows up to the Point of Zero Charge (PZC)
      and slowly decrease beyond. The adsorption capacities of the materials also
      increase proportionally with the initial phosphate concentration. The pseudo
      second-order successfully described the kinetics of the phosphate adsorption on
      the two adsorbents. With this model, the adsorption capacity values are obtained,
      which give an idea of the maximum phosphate uptake that the laterite and
      sandstone could achieve. The changes on the FTIR spectra of raw materials and
      phosphate adsorbed material confirm the mechanism of chemisorptions. Considering
      the above, laterite and sandstone could be used as efficient and cheap adsorbent
      for the removal of phosphate in aqueous solution.

PMID- 27692513
TI  - Cesium and strontium loads into a combined sewer system from rainwater runoff.
AB  - In this study, combined sewage samples were taken with time in several rain
      events and sanitary sewage samples were taken with time in dry weather to
      calculate Cs and Sr loads to sewers from rainwater runoff. Cs and Sr in rainwater
      were present as particulate forms at first flush and the particulate Cs and Sr
      were mainly bound with inorganic suspended solids such as clay minerals in
      combined sewage samples. In addition, multiple linear regression analysis showed
      Cs and Sr loads from rainwater runoff could be estimated by the total amount of
      rainfall and antecedent dry weather days. The variation of the Sr load from
      rainwater to sewers was more sensitive to total amount of rainfall and antecedent
      dry weather days than that of the Cs load.

PMID- 27692514
TI  - From municipal/industrial wastewater sludge and FOG to fertilizer: A proposal for
      economic sustainable sludge management.
AB  - After a ban on the depositing of untreated sludge in landfills, the sludge from
      municipal and industrial water-treatment plants can be regarded as a problem.
      Waste products of the water treatment process can be a problem or an opportunity 
      a source for obtaining raw materials. In the European Union, raw sludge and
      fats, oil and grease (FOG) from municipal and industrial wastewater treatment
      plants (WWTP) cannot be deposited in any natural or controlled environment. For
      this reason, it must be processed (stabilized, dried) to be used later as a
      fertilizer, building material, or alternative fuel source suitable for co
      incineration in high temperature furnaces (power plants or concrete plants). The
      processes of drying sludge, where heat and electricity are used, are energy
      consuming and economically unattractive. Beside energy efficiency, the main
      problem of sludge drying is in its variability of quality as a raw material. In
      addition to this, sludge can be contaminated by a number of organic and inorganic
      pollutants and organisms. Due to the presence or absence of pollutants, different
      end products can be economically interesting. For example, if the dried sludge
      contains coliform bacteria, viruses, helminths eggs or smaller quantities of
      heavy metals, it cannot be used as a fertilizer but can still be used as a fuel.
      The objectives of the current article is to present a batch-processing pilot
      device of sludge or digestate that allows the following: (1) low pressure and low
      temperature energy effective drying of from 10 to 40% remaining water content,
      (2) disinfection of pathogen (micro)organisms, (3) heavy metal reduction, (4)
      production of products of predetermined quality (e.g. containing different
      quantities of water; it can be used as a fertilizer, or if the percentage of
      water in the dry sludge is decreased to 10%, then the dried sludge can be used as
      a fuel with a calorific value similar to coal). An important feature is also the
      utilization of low-pressure technology to prevent odorous gasses from spreading
      into the environment. There are presented two new technologies: a) Sewage sludge
      or digestate drying in the vacuum chamber consumes approx. 1 kWh/dm3 of
      evaporated water and, therefore, reaches a price of 180-240 Euros/t Dry Matter
      (DM), and b) Heavy metals' reduction using adsorbing reaction with magnetite
      nanostructures can decrease the level of heavy metals in the sewage sludge or
      digestate up to 20% in one cycle, which can be repeated several times on the same
      sludge. The aim of the paper is to present a newly developed technology which can
      provide economic and safe use of moderate heavy metals polluted sewage sludge on
      agricultural lands as organic fertilizer and, therefore, returning the nutrients
      (nitrogen, phosphorous, potassium) back to the human food chain, instead of being
      incinerated or landfilled. The proposed drying technology is economically
      sustainable due to the low vacuum and temperature (35  degrees C-40  degrees C),
      that increases the efficiency of the heat pump (coefficient of performance 5-7,2)
      of the energy produced by the anaerobic digestion. Hence, the main emphasis is
      given to the development of: an efficient method for heavy metals' reduction in
      the sludge treatment chain by using chitosan covered magnetite nanoparticles, an
      efficient drying method in a vacuum with low temperature energy which can be
      exploited from sludge digestion to reduce organic matter, and an energy
      sustainable concept of sludge treatment, with the addition of fats, oil and
      grease (FOG) to produce enough biogas for sludge drying to produce fertilizer.

PMID- 27692515
TI  - Mapping discourses using Q methodology in Matang Mangrove Forest, Malaysia.
AB  - The sustainable management of natural resources requires the consideration of
      multiple stakeholders' perspectives and knowledge claims, in order to inform
      complex and possibly contentious decision-making dilemmas. Hence, a better
      understanding of why people in particular contexts do manage natural resources in
      a particular way is needed. Focusing on mangroves, highly productive tropical
      intertidal forests, this study's first aim is to map the diversity of subjective
      viewpoints among a range of stakeholders on the management of Matang Mangrove
      Forest in peninsular Malaysia. Secondly, this study aims to feed the reflection
      on the possible consequences of the diversity of perspectives for the future
      management of mangroves in Malaysia and beyond. The use of the semi-quantitative
      Q methodology allowed us to identify three main discourses on mangrove
      management: i. the optimization discourse, stressing the need to improve the
      current overall satisfactory management regime; ii. the 'change for the better'
      discourse, which focuses on increasingly participatory management and on
      ecotourism; and iii. the conservative 'business as usual' discourse. The
      existence of common points of connection between the discourses and their
      respective supporters provides opportunities for modifications of mangrove
      management regimes. Acknowledging this diversity of viewpoints, reflecting how
      different stakeholders see and talk about mangrove management, highlights the
      need to develop pro-active and resilient natural resource management approaches.

PMID- 27692516
TI  - Geotechnology and landscape ecology applied to the selection of potential forest
      fragments for seed harvesting.
AB  - The Atlantic Forest biome is recognized for its biodiversity and is one of the
      most threatened biomes on the planet, with forest fragmentation increasing due to
      uncontrolled land use, land occupation, and population growth. The most serious
      aspect of the forest fragmentation process is the edge effect and the loss of
      biodiversity. In this context, the aim of this study was to evaluate the dynamics
      of forest fragmentation and select potential forest fragments with a higher
      degree of conservation for seed harvesting in the Itapemirim river basin,
      Espirito Santo State, Brazil. Image classification techniques, forest landscape
      ecology, and multi-criteria analysis were used to evaluate the evolution of
      forest fragmentation to develop the landscape metric indexes, and to select
      potential forest fragments for seed harvesting for the years 1985 and 2013.
      According to the results, there was a reduction of 2.55% of the occupancy of the
      fragments in the basin between the years 1985 and 2013. For the years 1985 and
      2013, forest fragment units 2 and 3 were spatialized with a high potential for
      seed harvesting, representing 6.99% and 16.01% of the total fragments,
      respectively. The methodology used in this study has the potential to be used to
      support decisions for the selection of potential fragments for seed harvesting
      because selecting fragments in different environments by their spatial attributes
      provides a greater degree of conservation, contributing to the protection and
      conscious management of the forests. The proposed methodology can be adapted to
      other areas and different biomes of the world.

PMID- 27692517
TI  - Simultaneous detoxification and bioethanol fermentation of furans-rich synthetic
      hydrolysate by digestate-based pyrochar.
AB  - Pyrolysis is a sustainable pathway to transform renewable biomasses into both
      biofuels and advanced carbonaceous materials (i.e. pyrochar) which can be used as
      adsorbent of furan compounds. In particular, the aim of this study was to: i)
      evaluate the effect of vibro-ball milling on physical characteristics of pyrochar
      and its consequent performance on solely detoxification of a synthetic medium,
      containing furans and soluble sugars; ii) study the simultaneous detoxification
      and bioethanol fermentation, by adding activated pyrochar into fermentation
      medium. Results demonstrated that, compared to untreated pyrochar, the use of
      milled pyrochar increased by 52% furfural removal from the synthetic medium.
      Furfural removal rate was also increased (adsorption kinetic constant increased
      from 0.015 min-1 up to 0.215 min-1), at a pyrochar loading of 40 g L-1. Although,
      the simultaneous addition of pyrochar into the fermentation medium did not
      improve the bioethanol yield of the synthetic medium, it has significantly
      increased the bioethanol production rate.

PMID- 27692518
TI  - Treatment planning strategy for whole-brain radiotherapy with hippocampal sparing
      and simultaneous integrated boost for multiple brain metastases using intensity
      modulated arc therapy.
AB  - PURPOSE: To retrospectively evaluate the accuracy, plan quality and efficiency of
      intensity-modulated arc therapy (IMAT) for hippocampal sparing whole-brain
      radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in patients with
      multiple brain metastases (m-BM). MATERIALS AND METHODS: A total of 5 patients
      with m-BM were retrospectively replanned for HS-WBRT with SIB using IMAT
      treatment planning. The hippocampus was contoured on diagnostic T1-weighted
      magnetic resonance imaging (MRI) which had been fused with the planning CT image
      set. The hippocampal avoidance zone (HAZ) was generated using a 5-mm uniform
      margin around the paired hippocampi. The m-BM planning target volumes (PTVs) were
      contoured on T1/T2-weighted MRI registered with the 3D planning computed
      tomography (CT). The whole-brain planning target volume (WB-PTV) was defined as
      the whole-brain tissue volume minus HAZ and m-BM PTVs. Highly conformal IMAT
      plans were generated in the Eclipse treatment planning system for Novalis-TX
      linear accelerator consisting of high-definition multileaf collimators (HD-MLCs:
      2.5-mm leaf width at isocenter) and 6-MV beam. Prescription dose was 30Gy for WB
      PTV and 45Gy for each m-BM in 10 fractions. Three full coplanar arcs with orbit
      avoidance sectors were used. Treatment plans were evaluated using homogeneity
      (HI) and conformity indices (CI) for target coverage and dose to organs at risk
      (OAR). Dose delivery efficiency and accuracy of each IMAT plan was assessed via
      quality assurance (QA) with a MapCHECK device. Actual beam-on time was recorded
      and a gamma index was used to compare dose agreement between the planned and
      measured doses. RESULTS: All 5 HS-WBRT with SIB plans met WB-PTV D2%, D98%, and
      V30Gy NRG-CC001 requirements. The plans demonstrated highly conformal and
      homogenous coverage of the WB-PTV with mean HI and CI values of 0.33 +/- 0.04
      (range: 0.27 to 0.36), and 0.96 +/- 0.01 (range: 0.95 to 0.97), respectively. All
      5 hippocampal sparing patients met protocol guidelines with maximum dose and dose
      to 100% of hippocampus (D100%) less than 16 and 9Gy, respectively. The dose to
      the optic apparatus was kept below protocol guidelines for all 5 patients. Highly
      conformal and homogenous radiosurgical dose distributions were achieved for all 5
      patients with a total of 33 brain metastases. The m-BM PTVs had a mean HI = 0.09
      +/- 0.02 (range: 0.07 to 0.19) and a mean CI = 1.02 +/- 0.06 (range: 0.93 to
      1.2). The total number of monitor units (MU) was, on average, 1677 +/- 166. The
      average beam-on time was 4.1 +/- 0.4 minute . The IMAT plans demonstrated
      accurate dose delivery of 95.2 +/- 0.6%, on average, for clinical gamma passing
      rate with 2%/2-mm criteria and 98.5 +/- 0.9%, on average, with 3%/3-mm criteria.
      CONCLUSIONS: All hippocampal sparing plans were considered clinically acceptable
      per NRG-CC001 dosimetric compliance criteria. IMAT planning provided highly
      conformal and homogenous dose distributions for the WB-PTV and m-BM PTVs with
      lower doses to OAR such as the hippocampus. These results suggest that HS-WBRT
      with SIB is a clinically feasible, fast, and effective treatment option for
      patients with a relatively large numbers of m-BM lesions.

PMID- 27692519
TI  - [Inter-observer variability of decision concerning the route of delivery in case
      of one previous cesarean section and abnormal pelvic measures].
AB  - OBJECTIVES: To study inter-observer variability of decision concerning the route
      of delivery using pelvimetry in case of one previous cesarean section and
      abnormal pelvic measures. MATERIALS AND METHOD: Observational study conducted in
      2014 in 4 university maternity units among 36 obstetricians. Two groups of
      obstetricians - as they practiced in a center where pelvimetry was routinely
      performed (n=12) or not (n=24) - had to choose a route of delivery for 10
      clinical cases of women with a single uterine scar and a tight pelvis. The
      "routine pelvimetry" group had pelvimetry results. The group "no pelvimetry"
      became aware of pelvimetry results as a second step and had to indicate whether
      this information changed or not their management. The measurement of the inter
      observer variability was estimated by estimating the proportion of agreement
      according to Grant method. RESULTS: The proportion of agreements of an attempted
      vaginal delivery between obstetricians in the group "routine pelvimetry" was
      64.7% (95% CI [61-68.5]) and 97.3% (95% CI [96.4 to 98.3]) in the group "no
      pelvimetry", prior knowledge of pelvimetry results. An attempted vaginal delivery
      was decided in 77.5% versus 98.7% (P<0.001). After knowledge of pelvimetry
      results in the group "no pelvimetry" had, the number of attempted vaginal deliver
      was not different (77.5% vs. 78%, P=0.920). CONCLUSION: In women with one
      previous cesarean section, in case of tight pelvis discovered after pelvimetry,
      inter-observer variability of decision concerning the route of delivery is
      increased. Centers that choose to continue using the routine pelvimetry should
      develop procedures to limit this variability.

PMID- 27692520
TI  - [Placental site trophoblastic tumor: When do we suspect it and which treatment
      shall we decide?]
AB  - Tumors of trophoblast implantation site TTSI are rare gestational tumors. This
      case highlights the diagnostic difficulties and treatment of tumors of
      trophoblastic implantation site early. Patient of 28 years with no medical
      history, G1P1 who gave birth 11 months ago presented bleeding with an HCG level
      of 73IU that led to the diagnosis of early miscarriage. Treatment of miscarriage
      by hysteroscopy and curettage is complicated leading to the realization of an
      abdominopelvic CT and pelvic ultrasound that show an atypical uterine vascularity
      and an intracavitary heterogeneous mass. The pelvic MRI performed evokes a TTSI
      stage I. A hysterectomy with bilateral salpingectomy and ovarian conservation is
      achieved. Despite the standard treatment with surgery the HCG levels do not
      normalize before seven months after surgery. This indicates an adjuvant
      chemotherapy, the patient refuses. The presented case illustrates the diagnostic
      difficulties of the disease. He noted the importance of the second reading
      network proposed by the specialized center in Lyon. It also raises the question
      of adjuvant chemotherapy in some cases of early stage TTSI. The challenge is to
      define cases requiring adjuvant therapy. Predictors of chemotherapy in early
      stages could be tumor size, degree of infiltration of the myometrium and mutation
      p53. Amenorrhea, bleeding associated with uterine atypical vascularization, and
      atypical development of HCG<1000IU and/or unusual complications of treatment of
      miscarriage should evoke a tumor site trophoblastic implantation. Hysterectomy is
      the first treatment in early stages. Tumor size, degree of infiltration of the
      myometrium and mutation p53 are predictors to assess in multicentre studies to
      define the indications of postoperative chemotherapy.

PMID- 27692521
TI  - [Does hyperandrogenic statute in the polycystic ovary syndrome constitute an
      obstacle to the success of in vitro fertilization?]
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of initial
      androgenic statute of women with polycystic ovary syndrome (SOPK) on the expected
      results of in vitro fertilization (FIV). MATERIALS AND METHODS: It is about an
      exploratory study carried out in 61 unfertile SOPK patients, having profited all
      from a cycle of FIV/ICSI (intracytoplasmic sperm injection). We have divided our
      population in two groups according to their hormonal androgenic statute: groups
      with hyperandrogenism and without hyperandrogenism. We proceeded to note the
      anthropometric and hormonal parameters as well as results of FIV for each of the
      two groups. RESULTS: SOPK patients with hyperandrogenism are more obese than
      their counterparts. Also, they have more oocytes collected after ovarian
      induction. In addition, we did not reveal any significant differences between our
      two study groups concerning parameters defining FIV response. CONCLUSION: Our
      findings suggest that hyperandrogenism statute in SOPK infertile women does not
      seem to compromise the results of FIV. On the contrary, it would make it possible
      to optimize the chances to puncture more significant number of oocytes.

PMID- 27692524
TI  - Report of the Cent Gardes HIV Vaccines Conference, Part 2: The cellular immune
      response. Fondation Merieux Conference Center, Veyrier-du-Lac, France, 25-27
      October 2015.

PMID- 27692522
TI  - Structural, antigenic and immunogenic features of respiratory syncytial virus
      glycoproteins relevant for vaccine development.
AB  - Extraordinary progress in the structure and immunobiology of the human
      respiratory syncytial virus glycoproteins has been accomplished during the last
      few years. Determination of the fusion (F) glycoprotein structure folded in
      either the prefusion or the postfusion conformation was an inspiring breakthrough
      not only to understand the structural changes associated with the membrane fusion
      process but additionally to appreciate the antigenic intricacies of the F
      protein. Furthermore, these developments have opened new avenues for structure
      based designs of promising hRSV vaccine candidates. Finally, recent advances in
      our knowledge of the attachment (G) glycoprotein and its interaction with cell
      surface receptors have revitalized interest in this molecule as a vaccine, as
      well as its role in hRSV immunobiology.

PMID- 27692523
TI  - Development and clinical applications of novel antibodies for prevention and
      treatment of respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) remains a significant cause of morbidity and
      mortality in infants and young children, immunocompromised patients and the
      elderly. Despite the high disease burden, an effective and safe vaccine is
      lacking, although several candidates are currently in development. Current
      treatment for RSV infection remains largely supportive and RSV-specific options
      for prophylaxis are limited to palivizumab. In the past few years, novel
      therapeutic options including nanobodies, polyclonal and monoclonal antibodies
      have emerged and there are several products in preclinical and Phase-I, -II or 
      III clinical trials. The major target for antiviral drug development is the
      surface fusion (F) glycoprotein, which is crucial for the infectivity and
      pathogenesis of the virus. Solving the structures of the two conformations of the
      RSV F protein, the prefusion and postfusion forms, has revolutionized RSV
      research. It is now known that prefusion F is highly superior in inducing
      neutralizing antibodies. In this section we will review the stages of development
      and availability of different antibodies directed against RSV for the prevention
      and also for treatment of acute RSV infections. Some of these newer anti-RSV
      agents have shown enhanced potency, are being explored through alternative routes
      of administration, have improved pharmacokinetic profiles with an extended half
      life, and may reduce design and manufacturing costs. Management strategies will
      require targeting not only high-risk populations (including adults or
      immunocompromised patients), but also previously healthy children who, in fact,
      represent the majority of children hospitalized with RSV infection. Following
      treated patients longitudinally is essential for determining the impact of these
      strategies on the acute disease as well as their possible long-term benefits on
      lung morbidity.

PMID- 27692525
TI  - Adolescent confidence in immunisation: Assessing and comparing attitudes of
      adolescents and adults.
AB  - INTRODUCTION: There is limited knowledge of adolescent views and attitudes
      towards immunisation. Our study investigated adolescent attitudes to immunisation
      and compared differences in vaccination attitudes between adolescents and adults.
      METHODS: This study was a cross-sectional, national online survey. Recruitment
      was stratified by state and gender to ensure findings were nationally
      representative. Regression analyses were performed to assess and compare
      adolescent and adult views on vaccine benefits, community protection, risks, side
      effects, sources of information, and decision-making preference. RESULTS: In
      2013, 502 adolescents and 2003 adults completed the online survey. Lower levels
      of vaccine confidence were observed in adolescents with adolescents less likely
      to believe vaccines are beneficial and/or safe compared to adults (p=0.043).
      Compared to females, males were less confident of vaccine benefits (p<0.05) but
      less concern about vaccine side effects (p<0.05). Adolescents were more concerned
      about vaccine side effects than adults for pain (p<0.001), redness or swelling
      (p<0.001), and fever (p=0.006). Adolescents were less likely than adults to
      consider health professionals (p<0.001) and the media (e.g. internet) (p=0.010)
      as important sources of information, and were more likely to seek information
      from social networks (p<0.001) including families and schools. Although 62.0% of
      adolescents agreed that parents should make the decision about vaccination for
      them, adolescents were more likely to prefer a joint decision with parents
      (p<0.001) or by themselves (p=0.007) compared with adults. CONCLUSION:
      Adolescents have a lesser understanding of vaccine safety and benefits than
      adults and have higher concerns about potential vaccine reactions. Improving
      adolescent awareness and knowledge of the benefits and risks of vaccination
      through school-based educational programs may improve confidence in and uptake of
      vaccines for adolescents and increase vaccine confidence in the next generation
      of parents.

PMID- 27692526
TI  - Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study
      Assessing Double-masKed Uveitis TReAtment (SAKURA).
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal sirolimus in the
      treatment of noninfectious uveitis (NIU) of the posterior segment (i.e.,
      posterior, intermediate, or panuveitis). DESIGN: Phase III, randomized, double
      masked, active-controlled, 6-month study with intravitreal sirolimus.
      PARTICIPANTS: Adults with active NIU of the posterior segment (intermediate,
      posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects
      discontinued NIU medications before baseline, except for systemic
      corticosteroids, which were allowed only for those already receiving them at
      baseline and were rapidly tapered after baseline per protocol. METHODS:
      Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or
      880 MUg, administered on Days 1, 60, and 120. MAIN OUTCOME MEASURES: The primary
      efficacy outcome was the percentage of subjects with VH 0 response at Month 5
      (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH
      0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to
      a prednisone-equivalent dosage of <=5 mg/day), and changes in best-corrected
      visual acuity (BCVA). Adverse events during the double-masked treatment period
      are presented. RESULTS: A total of 347 subjects were randomized. Higher
      proportions of subjects in the intravitreal sirolimus 440 MUg (22.8%; P = 0.025)
      and 880 MUg (16.4%; P = 0.182) groups met the primary end point than in the 44
      MUg group (10.3%). Likewise, higher proportions of subjects in the 440 MUg
      (52.6%; P = 0.008) and 880 MUg (43.1%; P = 0.228) groups achieved a VH score of 0
      or 0.5+ than in the 44 MUg group (35.0%). Mean BCVA was maintained throughout the
      study in each dose group, and the majority of subjects receiving corticosteroids
      at baseline successfully tapered off corticosteroids (44 MUg [63.6%], 440 MUg
      [76.9%], and 880 MUg [66.7%]). Adverse events in the treatment and active control
      groups were similar in incidence, and all doses were well tolerated. CONCLUSIONS:
      Intravitreal sirolimus 440 MUg demonstrated a significant improvement in ocular
      inflammation with preservation of BCVA in subjects with active NIU of the
      posterior segment.

PMID- 27692527
TI  - Adalimumab for Treatment of Noninfectious Uveitis: Immunogenicity and Clinical
      Relevance of Measuring Serum Drug Levels and Antidrug Antibodies.
AB  - PURPOSE: To evaluate the rate of immunogenicity induced by adalimumab and its
      relationship with drug serum levels and clinical responses in patients with
      noninfectious uveitis. DESIGN: Prospective observational study. PARTICIPANTS:
      Consecutive patients from 1 referral center who initiated treatment with
      adalimumab for active noninfectious uveitis resistant to conventional therapy.
      METHODS: All patients received 40 mg adalimumab every other week. Patients were
      evaluated clinically and immunologically before and after 4, 8, and 24 weeks of
      treatment. MAIN OUTCOME MEASURES: Clinical evaluation included assessment of
      changes in visual acuity, degree of inflammation in the anterior chamber and
      vitreous cavity, central macular thickness, and retinal angiographic leakage.
      Immunologic evaluation included assessment of serum trough adalimumab and
      antibodies against adalimumab (AAA) levels and class II HLA typing. RESULTS:
      Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a
      favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved
      a complete response and 7 (28%) achieved a partial response. However, 7 of 25
      patients (28%) were considered nonresponders. Median trough adalimumab serum
      levels were higher in responders than in nonresponders (P < 0.001). We observed
      AAA positivity (AAA+) at least 1 time point in 8 of 25 patients (32%), including
      4 with transitory AAA and 4 with permanent AAA. In all patients with permanent
      AAA+, trough adalimumab levels became undetectable (P < 0.001). However, in
      patients who demonstrated transitory AAA+, no correlation was observed between
      AAA titers and adalimumab trough levels (P = 0.2).Concomitant immunosuppression
      did not show any protective effect on adalimumab immunogenicity in our cohort. An
      association between the presence of AAA+ and a worse uveitis outcome was observed
      only in patients with permanent AAA+, which correlated with undetectable
      adalimumab trough levels (P = 0.014). CONCLUSIONS: Treatment of noninfectious
      uveitis with adalimumab is associated with high rates of favorable clinical
      response. Overall, adalimumab trough levels were higher in responder patients.
      Development of permanent AAA was associated with undetectable trough adalimumab
      levels and worse uveitis outcome. Immunogenicity was more common in patients in
      whom uveitis was associated with a systemic disease and was not influenced by
      concomitant immunosuppressors.

PMID- 27692529
TI  - A principal component analysis of the relationship between the external body
      shape and internal skeleton for the upper body.
AB  - Recent progress in 3D scanning technologies allows easy access to 3D human body
      envelope. To create personalized human models with an articulated linkage for
      realistic re-posturing and motion analyses, an accurate estimation of internal
      skeleton points, including joint centers, from the external envelope is required.
      For this research project, 3D reconstructions of both internal skeleton and
      external envelope from low dose biplanar X-rays of 40 male adults were obtained.
      Using principal component analysis technique (PCA), a low-dimensional dataset was
      used to predict internal points of the upper body from the trunk envelope. A
      least squares method was used to find PC scores that fit the PCA-based model to
      the envelope of a new subject. To validate the proposed approach, estimated
      internal points were evaluated using a leave-one-out (LOO) procedure, i.e.
      successively considering each individual from our dataset as an extra-subject. In
      addition, different methods were proposed to reduce the variability in data and
      improve the performance of the PCA-based prediction. The best method was
      considered as the one providing the smallest errors between estimated and
      reference internal points with an average error of 8.3mm anterior-posteriorly,
      6.7mm laterally and 6.5mm vertically. As the proposed approach relies on few or
      no bony landmarks, it could be easily applicable and generalizable to surface
      scans from any devices. Combined with automatic body scanning techniques, this
      study could potentially constitute a new step towards automatic generation of
      external/internal subject-specific manikins.

PMID- 27692528
TI  - Pediatric Idiopathic Intracranial Hypertension: Age, Gender, and Anthropometric
      Features at Diagnosis in a Large, Retrospective, Multisite Cohort.
AB  - PURPOSE: To examine anthropometric and maturational characteristics at diagnosis
      in pediatric idiopathic intracranial hypertension (IIH). DESIGN: Retrospective,
      international, multisite study. PARTICIPANTS: Pediatric patients (2-18 years of
      age at diagnosis) with IIH. MAIN OUTCOME MEASURES: Body mass index (BMI), height,
      and weight Z-scores; sexual maturation. METHODS: Cases of IIH were identified
      retrospectively based on diagnostic code, pediatric neuro-ophthalmologist
      databases, or both and updated diagnostic criteria (2013) were applied to confirm
      definite IIH. Anthropometric measurements were converted into age- and gender
      specific height, weight, and BMI Z-scores CDC 2000 growth charts. When available,
      sexual maturation was noted. RESULTS: Two hundred thirty-three cases of definite
      IIH were identified across 8 sites. In boys, a moderate association between age
      and BMI Z-scores was noted (Pearson's correlation coefficient, 0.50; 95%
      confidence interval [CI], 0.30-0.66; P < 0.001; n = 72), and in girls, a weak
      association was noted (Pearson's correlation coefficient, 0.34; 95% CI, 0.20
      0.47; P < 0.001; n = 161). The average patient was more likely to be overweight
      at diagnosis at age 6.7 years in girls and 8.7 years in boys, and obese at
      diagnosis at age 12.5 years in girls and 12.4 years in boys. Compared with age-
      and gender-matched reference values, early adolescent patients were taller for
      age (P = 0.002 in girls and P = 0.02 in boys). Data on Tanner staging, menarchal
      status, or both were available in 25% of cases (n = 57/233). Prepubertal
      participants (n = 12) had lower average BMI Z-scores (0.95+/-1.98) compared with
      pubertal participants (n = 45; 1.92+/-0.60), but this result did not reach
      statistical significance (P = 0.09). CONCLUSIONS: With updated diagnostic
      criteria and pediatric-specific assessments, the present study identifies 3
      subgroups of pediatric IIH: a young group that is not overweight, an early
      adolescent group that is either overweight or obese, and a late adolescent group
      that is mostly obese. Data also suggest that the early adolescent group with IIH
      may be taller than age- and gender-matched reference values. Understanding these
      features of pediatric IIH may help to illuminate the complex pathogenesis of this
      condition.

PMID- 27692530
TI  - Total Skin Electron Beam Therapy in the Treatment of Mycosis Fungoides: A Review
      of Conventional and Low-Dose Regimens.
AB  - Mycosis fungoides (MF) is the most prevalent subtype of cutaneous T-cell
      lymphoma, which is characterized by the proliferation of CD4+ T cells. While
      often an indolent disease, most patients eventually develop progression from
      isolated patches to tumors and finally nodal or visceral involvement. Treatment
      choice is largely based on disease burden, though prognostic factors such as
      disease stage, patient age, and extracutaneous involvement must be taken into
      consideration. Radiotherapy represents one of the most effective therapeutic
      modalities in the treatment of MF. Lymphocytes are exquisitely radiosensitive,
      and excellent responses are observed even with low doses of radiation. Total skin
      electron beam therapy (TSEBT) is a special technique that allows for the
      homogenous irradiation of the entire skin. There are well-documented radiation
      dose-response relationships for achieving a complete response. As such, TSEBT
      doses >= 30 Gy comprise the current standard of care. Although highly effective,
      most patients experience recurrent disease even after conventional-dose (>= 30
      Gy) TSEBT. In addition, toxicity is cumulatively dose dependent, and there is
      reluctance to administer multiple courses of conventional-dose TSEBT.
      Consequently, there has been renewed interest in determining the utility of TSEBT
      at lower total (<= 30 Gy) doses. Advantages of low-total-dose (with standard dose
      per fraction) TSEBT include a shortened treatment course, the potential to
      minimize the risk of adverse events, and the opportunity to allow for retreatment
      in cases of disease recurrence. This comprehensive review compares the impact of
      different TSEBT dosing schemes on clinical outcomes of MF.

PMID- 27692531
TI  - Identification and quantification of nuisance odors at a trash transfer station.
AB  - The objective of this study was to evaluate the effectiveness of a modified Odor
      Profile Method (OPM) at a trash transfer station (TTS). An updated Landfill Odor
      Wheel was used to define odor character and distinguish among odor sources. The
      Flavor Profile Analysis (FPA) intensity scale was used to rank the relative
      intensity of the various odor characters defined by the odor wheel and to
      understand how each odor profile changed off site. Finally, the odor wheel was
      used to select the appropriate chemical analysis to identify the odorants causing
      the odors identified by the human panelists. The OPM was demonstrated as an
      effective tool for characterizing and distinguishing odor sources at a TTS.
      Municipal solid waste (MSW) odors were characterized as rancid, sulfur, and
      fragrant; rancid odors were dominant in the odor profile on-site, while sulfur
      odors dominated off-site. Targeted chemical analysis was used to identify
      odorants potentially responsible for odors at the site. Methyl mercaptan (rotten
      vegetable) and hydrogen sulfide (rotten egg) were identified as the odorants most
      likely to be responsible for the sulfur odors at the site. Acetaldehyde (sweet,
      fruity), acetic acid (vinegar), and butyric acid (rancid) were identified as the
      odorants mostly likely to be causing the rancid and sour odors. Terpenes/pine
      odors were observed near the greenwaste pile. Results confirm that the OPM,
      together with properly selected chemical analyses, can be a useful tool for
      identifying and quantifying the sources of odors.

PMID- 27692532
TI  - Retrievable Inferior Vena Cava Filters in Trauma Patients: Prevalence and
      Management of Thrombus Within the Filter.
AB  - OBJECTIVE: The incidence of thrombus was investigated within retrievable filters
      placed in trauma patients with confirmed DVT at the time of retrieval and the
      optimal treatment for this clinical scenario was assessed. A technique called
      "filter retrieval with manual negative pressure aspiration thrombectomy" for
      management of filter thrombus was introduced and assessed. METHODS: The
      retrievable filters referred for retrieval between January 2008 and December 2015
      were retrospectively reviewed to determine the incidence of filter thrombus on a
      pre-retrieval cavogram. The clinical outcomes of different managements for
      thrombus within filters were recorded and analyzed. RESULTS: During the study 764
      patients having Aegisy Filters implanted were referred for filter removal, from
      which 236 cases (134 male patients, mean age 50.2 years) of thrombus within the
      filter were observed on initial pre-retrieval IVC venogram 12-39 days after
      insertion (average 16.9 days). The incidence of infra-filter thrombus was 30.9%,
      and complete occlusion of the filter bearing IVC was seen in 2.4% (18) of cases.
      Retrieval was attempted in all 121 cases with small clots using a regular snare
      and sheath technique, and was successful in 120. A total of 116 cases with
      massive thrombus and IVC occlusion by thrombus were treated by CDT and/or the new
      retrieval technique. Overall, 213 cases (90.3%) of thrombus in the filter were
      removed successfully without PE. CONCLUSIONS: A small thrombus within the filter
      can be safely removed without additional management. CDT for reduction of the
      clot burden in filters was effective and safe. Filter retrieval with manual
      negative pressure aspiration thrombectomy seemed reasonable and valuable for
      management of massive thrombus within filters in some patients. Full assessment
      of the value and safety of this technique requires additional studies.

PMID- 27692533
TI  - 18FDG-PET-CT improves specificity of preoperative lymph-node staging in patients
      with intestinal but not diffuse-type esophagogastric adenocarcinoma.
AB  - INTRODUCTION: The accuracy of preoperative lymph-node staging in patients with
      adenocarcinoma of the esophagogastric junction (AEG) or gastric cancer (GC) is
      low. The aim of this study was to assess the accuracy of [18F]fluorodeoxyglucose
      positron emission tomography/computed tomography (PET-CT) for lymph-node staging
      in patients with AEG or GC, with or without neoadjuvant treatment. PATIENTS AND
      METHODS: 221 consecutive patients with GC (n = 88) or AEG (n = 133) were
      evaluated. Initial staging included endoscopic ultrasound (EUS), multidetector
      spiral CT (MDCT) and PET-CT. PET-CT was performed for restaging in patients after
      neoadjuvant treatment (n = 94). Systematic lymphadenectomy was routinely
      performed with histopathological assessment of individual mediastinal and
      abdominal lymph-node stations. Preoperative staging from EUS, MDCT, and PET-CT
      was correlated with histopathological results. RESULTS: PET-CT showed a high
      specificity (91%) and positive predictive value (89%) for the preoperative
      detection of lymph-node metastases. In comparison, EUS was more sensitive (73%
      versus 50%, P < 0.01) but less specific (60%, P < 0.01). In patients with
      intestinal/mixed-type tumors, PET-CT improved the detection of extra-regional
      lymph-node metastases (P = 0.01) and distant metastases (P = 0.01) compared to CT
      alone. In contrast, lymph-node assessment by PET/CT after neoadjuvant treatment
      (32%, P < 0.01) and in diffuse-type cancers (24%, P < 0.01) is futile because of
      low sensitivities. CONCLUSION: PET-CT does not improve the overall accuracy of N
      staging, but does improve specificity compared to EUS and MDCT in AEG and GC. We
      do not recommend routine PET-CT for the initial staging in patients with diffuse
      type cancer or for restaging of lymph nodes after neoadjuvant treatment.

PMID- 27692534
TI  - Hepatic vascular inflow occlusion is associated with reduced disease free
      survival following resection of colorectal liver metastases.
AB  - BACKGROUND: Hepatic vascular inflow occlusion (VIO) can be applied during
      resection of colorectal liver metastases (CRLM) to control intra-operative blood
      loss, but has been linked to accelerated growth of micrometastases in
      experimental models. This study aimed to investigate the effects of hepatic VIO
      on disease-free and overall survival (DFS and OS) in patients following resection
      for CRLM. METHODS: All patients who underwent liver resection for CRLM between
      January 2006 and September 2015 at our center were analyzed. Hepatic VIO was
      performed if deemed indicated by the operating surgeon and severe ischemia was
      defined as >=20 min continuous or >=45 min cumulative intermittent VIO. Cox
      regression analysis was performed to identify predictive factors for DFS and OS.
      RESULTS: A total of 208 patients underwent liver resection for CRLM. VIO was
      performed in 64 procedures (31%), and fulfilled the definition of severe ischemia
      in 40 patients. Patients with severe ischemia had inferior DFS (5-year DFS 32%
      vs. 11%, P < 0.01), and inferior OS (5-year OS 37% vs. 64%, P < 0.01). At
      multivariate analysis, a high clinical risk score (Hazard ratio (HR) 1.60 (1.08
      2.36)) and severe ischemia (HR 1.89 (1.21-2.97)) were independent predictors of
      worse DFS. Severe ischemia was not an independent predictor of OS. CONCLUSION:
      The present cohort study suggests that prolonged hepatic VIO during liver
      resection for CRLM was associated with reduced DFS. A patient-tailored approach
      seems advisable although larger studies should confirm these findings.

PMID- 27692535
TI  - Mortality, morbidity and healthcare expenditures after local tumour ablation or
      partial nephrectomy for T1A kidney cancer.
AB  - BACKGROUND: Local tumour ablation (LTA) may yield better perioperative outcomes
      than partial nephrectomy (PN), however the impact of each treatment on
      perioperative mortality and health care expenditures is unknown. The aim of the
      study was to compare mortality, morbidity and health care expenditures between
      LTA and PN. PATIENTS AND METHODS: A population-based assessment of 2471 patients
      with cT1a kidney cancer treated with either LTA or PN, between 2000 and 2009, in
      the SEER-Medicare database was performed. After propensity score matching, 30-day
      mortality, overall and specific complication rates, length of stay, readmission
      rates and health care expenditures according to LTA or PN were estimated.
      Multivariable logistic and linear models addressed the effect of each specific
      LTA approach on overall complication rates, length of stay, readmission rates and
      health care expenditures. RESULTS: The 30-day mortality was <2% after either LTA
      or PN (OR 2.27, p = 0.2). The overall complication rate was 21% after LTA and 40%
      after PN (OR 0.38, p < 0.001). Blood transfusions, infection/sepsis, wound
      infections, respiratory complications, gastrointestinal complications, acute
      kidney injury, and accidental puncture or laceration/foreign body left during
      procedure rates resulted lower after LTA relative to PN (all p < 0.05).
      Similarly, length of stay and health care expenditures resulted lower after LTA
      relative to PN (all p < 0.05). Conversely, readmission rate was not significantly
      different in LTA relative to PN (p = 0.1). CONCLUSIONS: Despite similar
      perioperative mortality, LTA is associated with lower complications rate, shorter
      length of stay and lower health care expenditure relative to PN.

PMID- 27692536
TI  - Sarcopenia in overweight and obese patients is a predictive factor for
      postoperative complication in gastric cancer: A prospective study.
AB  - BACKGROUND: Sarcopenia is a syndrome characterized by progressive and generalized
      loss of skeletal muscle mass and strength. This study aims to explore the
      prevalence of sarcopenia in overweight and obese gastric cancer (GC) patients and
      figured out the impacts of sarcopenia on the postoperative complication of
      overweight and obese GC patients. METHODS: According to the recommended body-mass
      index (BMI) for Asian populations by WHO, we conducted a prospective study of
      overweight and obese gastric cancer patients (BMI >= 23 kg/m2) under curative
      gastrectomy from August 2014 to December 2015. Including lumbar skeletal muscle
      index, handgrip strength and gait speed as the sarcopenic components were
      measured before surgery. Patients were followed up after gastrectomy to gain the
      actual clinical outcomes. Factors contributing to postoperative complications
      were analyzed by univariate and multivariate analysis. RESULTS: Total of 206
      overweight or obese patients were enrolled in this study, 14 patients were
      diagnosed sarcopenia and were demonstrated having significantly association with
      higher risk of postoperative complications, higher hospital costs, and higher
      rate of 30-days readmission compared with the non-sarcopenic ones. On the basis
      of univariate and multivariate analysis, sarcopenia was an independent risk
      factor for postoperative complication of overweight and obese patients with
      gastric cancer (P = 0.002). CONCLUSION: Sarcopenia is an independent predictor of
      postoperative complications in overweight or obese patients with gastric cancer
      after radical gastrectomy.

PMID- 27692537
TI  - Assessment of environment impacts of egg production chain using life cycle
      assessment.
AB  - In this study we have to deal with the assessment of environment impacts of
      laying hen in the Alborz province, Iran. This assessment was carried out for one
      kg of egg during a period of 420 days for 1000 chickens. Then due to significant
      consumption of diet during period of question, three main products including
      corn, soybean and wheat which are consist of 80 percent of the combination of
      laying chicken diet, also collected the information about their production and it
      has been evaluated the indicators of their environment individually and
      eventually, the results has been considered as a title for inputs of poultry.
      Data for production of inputs were taken from EcoInvent 2.0 database, and SimaPro
      software was used for analysis. Ten classification impacts including Abiotic
      Depletion potential, Acidification potential, Eutrophication potential, Global
      Warming potential for time horizon 100 years, Ozone Depletion potential, Human
      Toxicity potential, Freshwater and Marine Aquatic Eco-toxicity potential,
      Terrestrial Eco-toxicity potential, and Photochemical Oxidation potential were
      selected based on the CML 2 baseline 2000 V2/world, 1990/characterization method.
      Due to the results, for each kilograms of egg, 30/09 MJ and also the value of
      greenhouse gas emissions is 4/07 Kg CO2 eq was calculated. According to the
      obtained results, the production of diet has made the most negative charge of
      environment among the inputs.

PMID- 27692538
TI  - Cholesterol efflux capacity: A weak player in the complex plot of cardiac
      allograft vasculopathy.

PMID- 27692540
TI  - Sporadic inclusion body myositis misdiagnosed as idiopathic granulomatous
      myositis.
AB  - We present a case of a 65-year-old woman who was previously diagnosed with
      idiopathic granulomatous myositis and treated with immunosuppressive therapy for
      the next 10 years before a clinical diagnosis of inclusion body myositis was
      made. A review of the previously performed muscle biopsy showed most of the
      cardinal myopathologic features of sporadic inclusion body myositis, in addition
      to the granuloma. Her clinical course was strongly suggestive of inclusion body
      myositis with selective asymmetric weakness of forearm flexor muscles and
      quadriceps. This report highlights the importance of correlating clinical picture
      with muscle pathology changes along with judicious use of magnetic resonance
      imaging and serological studies to establish a definite diagnosis.

PMID- 27692539
TI  - Macrophage/monocyte-specific deletion of Ras homolog gene family member A (RhoA)
      downregulates fractalkine receptor and inhibits chronic rejection of mouse
      cardiac allografts.
AB  - BACKGROUND: The cellular and molecular mechanisms of chronic rejection of
      transplanted organs remain obscure; however, macrophages are known to play a
      critical role in the injury and repair of allografts. Among multiple factors
      influencing macrophage infiltration to allografts, the fractalkine chemokine (C
      X3-C motif) ligand 1(CX3CL1)/chemokine (C-X3-C motif) receptor 1 (CX3CR1)
      signaling pathway and actin cytoskeleton, which is regulated by a small guanosine
      5'-triphosphatase Ras homolog gene family member A (RhoA), are of the utmost
      importance. To define the role of macrophage/RhoA pathway involvement in chronic
      rejection, we generated mice with monocyte/macrophage-specific deletion of RhoA.
      METHODS: Hearts from BALB/c (H-2d) donors were transplanted into RhoAflox/flox
      (no Cre) and heterozygous Lyz2Cre+/-RhoAflox/flox recipients treated with
      cytotoxic T-lymphocyte-associated protein 4 immunoglobulin to inhibit early T
      cell response. Allografts were assessed for chronic rejection and
      monocyte/macrophage functions. RESULTS: The deletion of RhoA inhibited macrophage
      infiltration, neointimal hyperplasia of vasculature, and abrogated chronic
      rejection of the allografts. The RhoA deletion downregulated G protein-coupled
      fractalkine receptor CX3CR1, which activates the RhoA pathway and controls
      monocyte/macrophage trafficking into the vascular endothelium. This in turn
      promotes, through overproliferation and differentiation of smooth muscle cells in
      the arterial walls, neointimal hyperplasia. CONCLUSIONS: Our finding of
      codependence of chronic rejection on monocyte/macrophage CX3CR1/CX3CL1 and RhoA
      signaling pathways may lead to the development of novel anti-chronic rejection
      therapies.

PMID- 27692541
TI  - Stormy weather.

PMID- 27692542
TI  - Neurotoxicology of aging - Two extreme views and the optimist scientist in the
      middle.

PMID- 27692544
TI  - School-Based Health Centers' Presence: The Role of School and Community Factors.
AB  - INTRODUCTION: School-based health centers (SBHCs) offer an efficient mechanism
      for delivering health services to large numbers of underserved youth; however,
      their availability varies across communities. Data on sociocontextual variables
      were analyzed to investigate factors that inhibit and facilitate SBHCs. METHODS:
      Secondary data from 2012 to 2015 state databases were linked to examine the
      association between SBHCs' presence in California high schools and demand,
      resource, and political conservatism at the school and community levels that may
      influence where SBHCs are located and the number of provided health services.
      Data were analyzed in 2015 using hierarchical binary and Poisson models. RESULTS:
      Presence of a local non-school-based family planning clinic was the strongest
      correlate of SBHC presence. School size, percentage non-white, and percentage
      receiving free or reduced-price lunches were positively associated with SBHC
      presence. Percentage who voted Republican in the 2012 general election and teen
      pregnancy rates were negatively associated with SBHC presence. None of the
      predictors were associated with number of services provided by SBHCs.
      CONCLUSIONS: School and community factors appear to play a role in supporting or
      impeding the establishment of SBHCs. In addition to variables tapping
      communities' need for and resources available to support SBHCs, political
      conservatism appears to affect SBHC availability. SBHC advocates can use this
      information to understand where opportunities for growth might exist, identify
      collaborative partners, and prepare for challenges to supporting new SBHCs.
      Researchers may also use this information in evaluation studies to control for
      school-level confounders and develop appropriate comparison samples through
      matching procedures.

PMID- 27692543
TI  - Sustained Economic Hardship and Cognitive Function: The Coronary Artery Risk
      Development in Young Adults Study.
AB  - INTRODUCTION: The relationship between low income and worse health outcomes is
      evident, yet its association with cognitive outcomes is less explored. Most
      studies have measured income at one time and none have examined how sustained
      exposure to low income influences cognition in a relatively young cohort. This
      study examined the effect of sustained poverty and perceived financial difficulty
      on cognitive function in midlife. METHODS: Income data were collected six times
      between 1985 and 2010 for 3,383 adults from the Coronary Artery Risk Development
      in Young Adults prospective cohort study. Sustained poverty was defined by the
      percentage of time participants' household income was <200% of the federal
      poverty level-"never" in poverty, "0< to <1/3," ">=1/3 to <100%" or "all-time."
      In 2010, at a mean age of 50 years, participants underwent a cognitive battery.
      Data were analyzed in 2015. RESULTS: In demographic-adjusted linear regression
      models, individuals with all-time poverty performed significantly worse than
      individuals never in poverty: 0.92 points worse on verbal memory (z-score, -0.28;
      95% CI=-0.43, -0.13), 11.60 points worse on processing speed (z-score, -0.72; 95%
      CI=-0.85, -0.58), and 3.50 points worse on executive function (z-score, -0.32;
      95% CI=-0.47, -0.17). Similar results were observed with perceived financial
      difficulty. Findings were robust when restricted to highly educated participants,
      suggesting little evidence for reverse causation. CONCLUSIONS: Cumulative
      exposure to low income over 2 decades was strongly associated with worse
      cognitive function of a relatively young cohort. Poverty and perceived hardship
      may be important contributors to premature aging among disadvantaged populations.

PMID- 27692546
TI  - Identification of methionine aminopeptidase 2 as a molecular target of the
      organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory
      activity and molecular modeling study.
AB  - A collection of twenty-six organoselenium compounds, ebselen and its structural
      analogues, provided a novel approach for inhibiting the activity of human
      methionine aminopeptidase 2 (MetAP2). This metalloprotease, being responsible for
      the removal of the amino-terminal methionine from newly synthesized proteins,
      plays a key role in angiogenesis, which is essential for the progression of
      diseases, including solid tumor cancers. In this work, we discovered that
      ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti
      oxidant and cytoprotective activity, inhibits one of the main enzymes in the
      tumor progression pathway. Using three-step synthesis, we obtained twenty-five
      ebselen derivatives/analogues, ten of which are new, and tested their inhibitory
      activity toward three neutral aminopeptidases (MetAP2, alanine and leucine
      aminopeptidases). All of the tested compounds proved to be selective, slow
      binding inhibitors of MetAP2. Similarly to ebselen, most of its analogues
      exhibited a moderate potency (IC50=1-12MUM). Moreover, we identified three strong
      inhibitors that bind favorably to the enzyme with the half maximal inhibitory
      concentration in the submicromolar range.

PMID- 27692545
TI  - Design, synthesis, and biological evaluation of alpha-hydroxyacyl-AMS inhibitors
      of amino acid adenylation enzymes.
AB  - Biosynthesis of bacterial natural-product virulence factors is emerging as a
      promising antibiotic target. Many such natural products are produced by
      nonribosomal peptide synthetases (NRPS) from amino acid precursors. To develop
      selective inhibitors of these pathways, we have previously described aminoacyl
      AMS (sulfamoyladenosine) macrocycles that inhibit NRPS amino acid adenylation
      domains but not mechanistically-related aminoacyl-tRNA synthetases. To improve
      the cell permeability of these inhibitors, we explore herein replacement of the
      alpha-amino group with an alpha-hydroxy group. In both macrocycles and
      corresponding linear congeners, this leads to decreased biochemical inhibition of
      the cysteine adenylation domain of the Yersina pestis siderophore synthetase
      HMWP2, which we attribute to loss of an electrostatic interaction with a
      conserved active-site aspartate. However, inhibitory activity can be regained by
      installing a cognate beta-thiol moiety in the linear series. This provides a path
      forward to develop selective, cell-penetrant inhibitors of the biosynthesis of
      virulence factors to probe their biological functions and potential as
      therapeutic targets.

PMID- 27692547
TI  - Synthesis and activity of newly designed aroxyalkyl or aroxyethoxyethyl
      derivatives of piperazine on the cardiovascular and the central nervous systems.
AB  - In the search for new hypotensive agents some new aroxyalkyl or aroxyethoxyethyl
      derivatives of piperazine have been synthesized and evaluated for their
      pharmacological properties. Pharmacological tests included receptor binding
      assays toward adrenergic receptors alpha1, alpha2 and beta1, additionally 5-HT1A,
      functional bioassay and in vivo evaluation of hypotensive activity as well as
      antidepressant-like potential. All the tested compounds exhibited alpha1
      antagonistic properties, three of them possessed also hypotensive activity in
      rats. The most promising compound 3 1-[4-(2,6-dimethylphenoxy)butyl]-4-(2
      methoxyphenyl)piperazine hydrochloride was a selective alpha1 receptor antagonist
      (Ki=23.5+/-1.3, alpha1/alpha2=15.77, pKB=8.538+/-0.109). It was active in all
      tested doses in vivo (1, 0.5, and 0.1mg/kg) and it reduced blood pressure by 10
      13% at the dose of 1mg/kg (rats, i.v.). Compound 5 1-[2-(2,3
      dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine dihydrochloride
      exhibited the lowest dose for antidepressant-like activity 5mg/kgb.w. (mice,
      i.p.) without influence on spontaneous activity (mice, i.p.).

PMID- 27692548
TI  - When in infancy does the "fear bias" develop?
AB  - Much research has focused on how infants respond to emotional facial expressions.
      One of the key findings in this area of research is that by 7months of age, but
      not younger, infants show a bias in processing fearful faces even when compared
      with other negative and novel facial expressions. A recent study by Heck and
      colleagues (Journal of Experimental Child Psychology, 2016, Vol. 147, pp. 100
      110) challenges this idea by showing that 5-month-olds looked longer at fearful
      faces than at happy and at neutral faces when dynamic displays (videos) are used.
      Given that previous work failed to find enhanced attention to fearful faces in 5
      month-olds using static displays (photographs), this was taken as evidence that
      biased attention to fear can be observed earlier when dynamic information is
      presented. However, we computed an analysis indicating that the overall amount of
      motion displayed in the videos in Heck and colleagues' study is confounded with
      emotion such that the greatest amount of motion is evident in the fearful face
      videos and may have driven infants' looking patterns. We discuss these findings
      and their limitations in the context of other research using dynamic emotion
      stimuli. Although these findings do not rule out the possibility that 5-month
      olds are sensitive to fear, we stress the need to control for physical
      differences such as motion before any conclusions regarding the emergence of the
      fear bias during infancy can be drawn and in order to improve research practice
      in the field.

PMID- 27692549
TI  - [A pseudotumoral lesion revealing Meckel's diverticulum].
AB  - INTRODUCTION: Meckel's diverticulum is a common malformation in children, usually
      asymptomatic, with complications in only 20% of cases. Exceptionally, a tumor can
      develop in Meckel's diverticulum in children, particularly Burkitt's lymphoma; in
      adults it can develop into a gastrointestinal stromal tumor, a leiomyosarcoma, or
      a neuroendocrine tumor such as a carcinoid tumor. The diagnosis of inflammatory
      pseudotumor following an insidious perforation is rare. OBSERVATION: We report
      the case of a 14-month-old boy who presented with fever, asthenia, food refusal,
      and digestive complaints such as vomiting and tender abdomen suggesting
      appendicitis. Computed tomography showed an ileal mass of 3cm in diameter, which
      led to the suspicion of Burkitt's lymphoma. Laparoscopy showed Meckel's
      diverticulum with a mass of 3*2.8*2cm. Histological examination confirmed the
      diagnosis of Meckel's diverticulum with gastric heterotopia and showed a
      proliferation of spindle cells in a myxoid background, with an inflammatory
      infiltrate made of lymphocytes and plasmocytes. Immunostaining ruled out a
      malignant tumor. The diagnosis of an inflammatory pseudotumor developing on a
      Meckel diverticulum with gastric heterotopias was made. The outcome was favorable
      after surgical resection. CONCLUSION: While perforation of a Meckel diverticulum
      with gastric heterotopia is a common finding, the discovery of an inflammatory
      pseudotumor following a perforation is rare; the differential diagnosis should
      include Burkitt's lymphoma.

PMID- 27692550
TI  - [Psychosocial issues of mothers whose children have sickle cell disease].
AB  - OBJECTIVES: To study and describe the psychological responses (depression and
      anxiety), the coping strategies, and the impact of sickle cell disease on the
      quality of life (QOL) of mothers. PATIENTS AND METHODS: A cross-sectional study
      of mothers with affected children was conducted at the university hospital center
      of Brazzaville, between February and April 2014. Hamilton and Beck scales, the
      Brief-COPE, and the Short Form Health Survey were used to assess anxiety,
      depression, coping strategies, and QOL, respectively. RESULTS: In all, 104
      mothers of children with sickle cell disease were surveyed. Of the subjects, 73
      (70.2%) had depression and 85 (81.7%) anxiety, while 19 (18.3%) mothers were
      neither anxious nor depressed. The study shows that depression occurred more
      often among mothers whose children presented with at least three vaso-occlusive
      crises (CVO) requiring hospitalization per year (OR=5.1; range=1.8-13.9), at
      least one blood transfusion (OR=6; range=2.3-15.5), and those whose disease had
      been known for at least 5 years (OR=3; range=1.2-7.2). On the contrary, maternal
      anxiety was influenced only by the number of transfusions and CVO requiring
      hospitalization. The main coping strategy was religious coping (65.4%) followed
      by acceptance (60%). The QOL of mothers with affected children was impaired in
      56.7% of cases. Altered QOL was related to the number of hospitalized CVO per
      year, i.e., equal to or greater than 3 (OR=6.5; range=2.1-19.6 [P<0.01]), and the
      number of blood transfusions equal to or greater than 1 (OR=2.9; range=1.2-7.3
      [P<0.025]). CONCLUSION: Sickle cell disease is a heavy burden for mothers caring
      for these children. Mental health disorders are present at the time of diagnosis
      and in everyday life.

PMID- 27692551
TI  - [Forensic issues raised by circumcision: Review and case report].
AB  - Circumcision is defined as the partial or total excision of the prepuce. It is
      one of the most frequently performed surgical procedures around the world. This
      practice primarily involves minors. The aim of this study was to review the legal
      aspects of ritual circumcision in France. We report the cases of an 11-year-old
      and a 15-year-old boy examined in the forensic unit at the Hotel-Dieu hospital in
      Paris, after their father complained to the Minors Protection Brigade of Paris
      following the discovery of their circumcision. The examination conducted in the
      forensic unit found that the two boys had undergone recent circumcision. The
      total incapacity of work (ITT) was assessed as 5 days for the 15-year-old boy and
      1 day for the 11-year-old boy. Ritual "medicalized" circumcision is legal in
      France, and does not fall under article 222-1 of the Criminal Code (torture and
      acts of barbarism) or article 16-1 of the Civil Code (inviolability of the human
      body). Circumcision is treated as a "serious act" by several areas of
      jurisprudence, which means it is imperative to obtain the consent of both
      parents. Moreover, it must be performed in a hospital by knowledgeable staff.

PMID- 27692552
TI  - [Desmoid tumors in an adolescent girl with familial adenomatous polyposis].
AB  - Desmoid tumors (DT) are rare and nonmetastasizing fibroblastic neoplasms,
      characterized by local invasiveness. They occur sporadically or arise in the
      context of familial adenomatous polyposis (FAP; 5-10% of cases). Most cases
      develop sporadically in young adults, but some cases also occur in children. We
      report the case of an adolescent girl with FAP and DT, and we discuss the
      therapeutic strategies. An adolescent girl with FAP underwent surgery at the age
      of 14 years with total proctocolectomy. She had a neo-mutation in the APC gene at
      codon 1068, which is not usually associated with DT. Three years later, she had
      painful defecations. Imaging showed two abdominal DT. After a multidisciplinary
      team meeting, the patient was refused for surgery, and medical treatment with
      antihormonal agents and nonsteroidal anti-inflammatory drugs was started. Imaging
      18 months later showed DT stabilization, but the patient had difficulties to
      control chronic pains, which required morphine treatment, hypnotic sessions, and
      transcutaneous electric nerve stimulation. This case highlights the importance of
      DT screening in patients with FAP, mainly after surgery, regardless of their age
      and genetic mutation. Progress remains to be made in determining DT risk factors
      and in developing treatment. DT are still difficult to cure because of their
      potential for local invasion and local recurrence, and need to be managed by a
      multidisciplinary team.

PMID- 27692553
TI  - [Accidental mercury poisoning in a 12-year-old girl].
AB  - INTRODUCTION: Exposure to metallic mercury can cause severe accidental
      intoxications in children, whose clinical symptoms can vary depending on the
      route of administration, the dose, as well as the time and duration of the
      exposure. It has become unusual in France, yet it must be considered when taking
      a patient's medical history in cases of multisystemic involvement without a clear
      explanation. CLINICAL CASE: We report the case of a 12-year-old patient
      hospitalized because of a cough, poor general condition, chills, night sweats,
      psychomotor retardation, and skin lesions that had been developing for several
      weeks. The initial clinical examination also revealed sinus tachycardia, arterial
      hypertension, and abolition of osteotendinous reflexes. Complementary examination
      results were normal apart from a glomerular proteinuria without renal failure.
      When interviewing the mother, she reported that the child had played with mercury
      balls 3 months earlier. The suspicion of poisoning was confirmed by blood and
      urine analysis as well as renal biopsy showing an aspect of membranous
      glomerulonephritis with IgG and C3 depositions. An intoxication via a transdermal
      route being unlikely on healthy skin, the Regional Health Agency's survey
      concluded that chronic intoxication had occurred by inhalation of the mercury
      spread on the floor at the time of the exposure, which was then vacuum cleaned
      and released again by the contaminated vacuum cleaner. The patient's outcome was
      favorable within a few weeks after initiating DMSA chelation therapy. CONCLUSION:
      Mercury poisoning should be considered in cases of a multisystemic disorder
      without clear explanation, in order to intervene quickly and thus prevent
      irreversible renal and neurological consequences.

PMID- 27692554
TI  - Optimize CA19-9 in detecting pancreatic cancer by Lewis and Secretor genotyping.
AB  - BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is currently the most widely used
      biomarker for pancreatic cancer. It is well-known that Lewis and Secretor status
      can affect CA19-9 biosynthesis. This study was performed to optimize CA19-9 in
      detecting pancreatic cancer using Lewis and Secretor dependent cut-off values.
      METHODS: Lewis and Secretor genotypes were determined by Sanger sequencing in a
      large cohort of subjects (578 cases with pancreatic cancer, 210 cases with benign
      pancreatic disease, 315 normal subjects). The effectiveness of CA19-9 for
      detecting pancreatic cancer using Lewis and Secretor group dependent cut-off
      values was evaluated. RESULTS: The Lewis (-), Mixed, and Secretor (-) groups had
      low, medium, and high CA19-9 biosynthesis, respectively. In Lewis (-) pancreatic
      cancer (all stages), CA19-9 had a sensitivity of 48.6% and a specificity of 95.9%
      when 1.8 U/mL was used as the cut-off value. The sensitivity of CA19-9 in
      detecting all stages of pancreatic cancer improved from 80.1% to 88.0% and the
      negative predictive value increased from 81.2% to 87.1% without compromising
      other values when using group dependent cut-off values. The sensitivity of CA19-9
      for the detection of stage I, II pancreatic cancer increased from 76.1% to 87.2%.
      CONCLUSIONS: The value of CA19-9 in detecting pancreatic cancer was optimized by
      using group dependent cut-off values based on Lewis and Secretor genotypes. CA19
      9 can be applied as an early detector of pancreatic cancer using group dependent
      cut-off values.

PMID- 27692555
TI  - Matrix metalloproteinase inhibitor modulates esterase-catalyzed degradation of
      resin-dentin interfaces.
AB  - OBJECTIVE: Assess the modulating effect of matrix metalloproteinase (MMP)
      inhibition on simulated human salivary enzyme (SHSE)-catalyzed degradation of
      interfacial fracture-toughness (FT) of self-etched and total-etched resin-dentin
      interfaces. METHODS: Miniature short-rod FT specimens (N=10/group) containing a
      resin composite bonded to human dentin, using a self-etch (Easy Bond, EB) or a
      total-etch (Scotchbond, SB) adhesives, were prepared with and without application
      of an MMP inhibitor (galardin). Specimens were non-incubated or incubated in
      phosphate buffered saline (PBS) or SHSE for 7, 30, 90, or 180-days. FT data were
      obtained using a universal testing machine. Incubation media were analyzed by
      high performance liquid chromatography (HPLC) for the presence of a 2,2-bis-[4
      2(2-hydroxy-3-methacryloxypropoxy)phenyl]-propane (bisGMA)-derived degradation
      product, bis-hydroxy-propoxy-phenyl-propane (bisHPPP). Fractographic analysis was
      performed by scanning electron microscopy and image processing software (ImageJ).
      Statistical analysis was performed by ANOVA and Tukey's (p<0.05). RESULTS: More
      bisHPPP was detected in SHSE vs. PBS for both adhesive systems (p<0.05). EB
      specimens yielded no difference in FT and failed preferentially in the resin
      after >30-days (p<0.05). SB specimens yielded lower FT values after 180-days with
      SHSE +/-galardin vs. 0-days/no-galardin (p<0.05) and failed preferentially in the
      hybrid-layer after >30-days (p<0.05). Galardin mildly modulated the change in
      fracture mode for both systems. SIGNIFICANCE: Esterase-catalyzed degradation of
      total-etch interfaces is modulated by MMP-inhibition, however, self-etch
      interfaces possess greater biostability under simulated intra-oral conditions,
      regardless of MMP inhibition. This could be related to different chemical
      compositions and/or mode of adhesion.

PMID- 27692556
TI  - Long-term Survival Analysis of Meniscus Allograft Transplantation With Bone
      Fixation.
AB  - PURPOSE: To investigate the long-term clinical results and clinical survival rate
      of meniscus allograft transplantation (MAT) with bone fixation. METHODS: The
      inclusion criteria of this study were previous MAT with bone fixation technique
      in our institution and minimum follow-up duration of 8 years. Potential subjects
      were identified using the medical records and database that was prospectively
      collected from December 1996 to December 2005. The exclusion criteria were
      diffuse International Cartilage Repair Society grade IV articular cartilage
      degeneration that was not treated with a concomitant or staged cartilage repair
      procedure. Surgical indication for MAT was previous total or subtotal
      meniscectomy followed by persistent swelling and pain in involved compartment.
      Recommendations to return to contact sports or strenuous activities were not
      made. Clinical outcomes were evaluated using the modified Lysholm score, and
      comparison between preoperative and final Lysholm score was done using Student t
      test. During the follow-up period, failure was defined as (1) subtotal resection
      of the allograft, (2) conversion to total knee arthroplasty, or (3) a modified
      Lysholm score less than 65 or that of the preoperative status. Survival analysis
      was performed using the Kaplan-Meier method. RESULTS: During the study period, 52
      knees underwent MAT in our institution and 49 knees were eligible for this study.
      Three knees were excluded because they had diffuse grade IV cartilage
      degeneration in the respective compartment. Among the 49 knees enrolled, 34
      underwent lateral and 15 underwent medial MAT. Two patients had bilateral lateral
      MAT. Of those 47 patients, 37 were male and 10 were female. Mean patient age at
      the time of the MAT was 30.4 +/- 8.6 years. The median follow-up period was 11.5
      years (8 to 17 years). The preoperative mean modified Lysholm score was 73.2 +/-
      10.6, which significantly increased to 89.4 +/- 13.2 at the time of the final
      follow-up (P < .001). There were 2 failures noted at 6 months and 11.3 years,
      respectively, after MAT. All of the other allografts were surviving at the time
      of the latest follow-up. The 10-year survival rate was 98.0% (95% confidence
      interval [CI], 94.1%-100%), and the 15-year survival rate was 93.3% (95% CI,
      83.7%-100%) according to the Kaplan-Meier analysis. CONCLUSIONS: MAT using the
      bone fixation techniques demonstrated a high clinical survival rate according to
      the long-term observation. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 27692557
TI  - The Development of a Xenograft-Derived Scaffold for Tendon and Ligament
      Reconstruction Using a Decellularization and Oxidation Protocol.
AB  - PURPOSE: To evaluate the biological, immunological, and biomechanical properties
      of a scaffold derived by architectural modification of a fresh-frozen porcine
      patella tendon using a decellularization protocol that combines physical,
      chemical, and enzymatic modalities. METHODS: Porcine patellar tendons were
      processed using a decellularization and oxidation protocol that combines
      physical, chemical, and enzymatic modalities. Scaffolds (n = 88) were compared
      with native tendons (n = 70) using histologic, structural (scanning electron
      microscopy, porosimetry, and tensile testing), biochemical (mass spectrometry,
      peracetic acid reduction, DNA quantification, alpha-galactosidase [alpha-gal]
      content), as well as in vitro immunologic (cytocompatibility, cytokine induction)
      and in vivo immunologic nonhuman primate analyses. RESULTS: A decrease in
      cellularity based on histology and a significant decrease in DNA content were
      observed in the scaffolds compared with the native tendon (P < .001). Porosity
      and pore size were increased significantly (P < .001). Scaffolds were
      cytocompatible in vitro. There was no difference between native tendons and
      scaffolds when comparing ultimate tensile load, stiffness, and elastic modulus.
      The alpha-gal xenoantigen level was significantly lower in the decellularized
      scaffold group compared with fresh-frozen, nondecellularized tissue (P < .001).
      The in vivo immunological response to implanted scaffolds measured by tumor
      necrosis factor-alpha and interleukin-6 levels was significantly (P < .001)
      reduced compared with untreated controls in vitro. These results were confirmed
      by an attenuated response to scaffolds in vivo after implantation in a nonhuman
      primate model. CONCLUSIONS: Porcine tendon was processed via a method of
      decellularization and oxidation to produce a scaffold that possessed
      significantly less inflammatory potential than a native tendon, was biocompatible
      in vitro, of increased porosity, and with significantly reduced amounts of alpha
      gal epitope while retaining tensile properties. CLINICAL RELEVANCE: Porcine
      derived scaffolds may provide a readily available source of material for
      musculoskeletal reconstruction and repair while eliminating concerns regarding
      disease transmission and the morbidity of autologous harvest.

PMID- 27692558
TI  - Impact of omega-3 polyunsaturated fatty acids on vascular function and blood
      pressure: Relevance for cardiovascular outcomes.
AB  - AIMS: To overview the effects of omega-3 polyunsaturated fatty acids (PUFA) on
      blood vessels and blood pressure (BP) and their relevance for cardiovascular
      prevention. DATA SYNTHESIS: The importance of omega-3 PUFA for the cardiovascular
      system has come under the spotlight during the last decades. These fatty acids
      are present in variable amounts in cell membranes of mammal species, and their
      content affects a variety of cellular functions. Evidence obtained in animal and
      human studies suggests that omega-3 PUFA affect many steps of the atherosclerotic
      process. In blood vessels, omega-3 PUFA improve endothelial function; promote
      vasodilatation through relaxation of smooth muscle cells; exert antioxidant, anti
      inflammatory, and antithrombotic actions; delay development of plaques and
      increase their stability; and decrease wall stiffening. Omega-3 PUFA might affect
      BP, and studies conducted with ambulatory monitoring suggest that supplementation
      with these fatty acids decreases the average 24-h BP levels. This effect on BP is
      related to the pretreatment membrane content of omega-3 PUFA, and this might
      explain some inconsistencies among intervention trials. Meta-analyses indicate
      that omega-3 PUFA have a mild but significant BP lowering effect. While
      encouraging results were initially obtained with the use of omega-3 PUFA
      supplements in secondary prevention trials, meta-analyses have not confirmed the
      ability of these fatty acids to decrease the risk of coronary heart and
      cerebrovascular disease. CONCLUSIONS: Omega-3 PUFA are associated with
      significant improvement in vascular function and lowering of BP. However, the
      evidence currently supporting the role of these fatty acids in cardiovascular
      prevention is weak and needs further investigation.

PMID- 27692559
TI  - Human parainfluenza virus-3 can be targeted by rapidly ex vivo expanded T
      lymphocytes.
AB  - BACKGROUND AIMS: Human parainfluenza virus-3 (HPIV) is a common cause of
      respiratory infection in immunocompromised patients and currently has no
      effective therapies. Virus-specific T-cell therapy has been successful for the
      treatment or prevention of viral infections in immunocompromised patients but
      requires determination of T-cell antigens on targeted viruses. METHODS: HPIV3
      specific T cells were expanded from peripheral blood of healthy donors using a
      rapid generation protocol targeting four HPIV3 proteins. Immunophenotyping was
      performed by flow cytometry. Viral specificity was determined by interferon (IFN)
      gamma ELISpot, intracellular cytokine staining and cytokine measurements from
      culture supernatants by Luminex assay. Cytotoxic activity was tested by 51Cr
      release and CD107a mobilization assays. Virus-specific T cells targeting six
      viruses were then produced by rapid protocol, and the phenotype of HPIV3-specific
      T cells was determined by immunomagnetic sorting for IFN-gamma-producing cells.
      RESULTS: HPIV3-specific T cells were expanded from 13 healthy donors. HPIV3
      specific T cells showed a CD4+ predominance (mean CD4:CD8 ratio 2.89) and
      demonstrated specificity for multiple HPIV3 antigens. The expanded T cells were
      polyfunctional based on cytokine production but only had a minor cytotoxic
      component. T cells targeting six viruses in a single product similarly showed
      HPIV3 specificity, with a predominant effector memory phenotype (CD3+/CD45RA
      /CCR7-) in responder cells. DISCUSSION: HPIV3-specific T cells can be produced
      using a rapid ex vivo protocol from healthy donors and are predominantly CD4+ T
      cells with Th1 activity. HPIV3 epitopes can also be successfully targeted
      alongside multiple other viral epitopes in production of six-virus T cells,
      without loss of HPIV3 specificity. These products may be clinically beneficial to
      combat HPIV3 infections by adoptive T-cell therapy in immune-compromised
      patients.

PMID- 27692560
TI  - Intake of different types of dairy and its prospective association with risk of
      type 2 diabetes: The Rotterdam Study.
AB  - BACKGROUND AND AIMS: The prevalence of type 2 diabetes (T2DM) is increasing.
      Several studies have suggested a beneficial effect of several major dairy
      nutrients on insulin production and sensitivity. Conversely, harmful effects have
      been suggested as well. This study aimed to investigate the impact of the full
      range of dairy products and its association with incidence T2DM in Dutch adults
      aged >=55 years participating in the Rotterdam Study. METHODS AND RESULTS: Dairy
      intake was assessed with a validated FFQ, including total, skimmed, semi-skimmed,
      full-fat, fermented, and non-fermented dairy, and subclasses of these product
      groups. Verified prevalent and incident diabetes were documented. Cox
      proportional hazards regression and spline regression were used to analyse data,
      adjusting for age, sex, alcohol, smoking, education, physical activity, body mass
      index, intake of total energy, energy-adjusted meat, and energy-adjusted fish
      intake. Median total dairy intake was 398 g/day (IQR 259-559 g/day). Through 9.5
      +/- 4.1 years of follow-up, 393 cases of incident T2DM were reported. Cox and
      spline regression did not point towards associations of total dairy consumption,
      dairy consumption based on fat content, non-fermented or fermented dairy
      consumption, or individual dairy product consumption with incident T2DM. The HR
      for total dairy intake and T2DM was 0.93 (95% CI: 0.70-1.23) in the upper
      quartile (P-for trend 0.76). CONCLUSIONS: This prospective cohort study did not
      point towards an association between dairy consumption and T2DM.

PMID- 27692561
TI  - Renal perfusion in sepsis: from macro- to microcirculation.
AB  - The pathogenesis of sepsis-associated acute kidney injury is complex and likely
      involves perfusion alterations, a dysregulated inflammatory response, and
      bioenergetic derangements. Although global renal hypoperfusion has been the main
      target of therapeutic interventions, its role in the development of renal
      dysfunction in sepsis is controversial. The implications of renal hypoperfusion
      during sepsis probably extend beyond a simple decrease in glomerular filtration
      pressure, and targeting microvascular perfusion deficits to maintain tubular
      epithelial integrity and function may be equally important. In this review, we
      provide an overview of macro- and microcirculatory dysfunction in experimental
      and clinical sepsis and discuss relationships with kidney oxygenation,
      metabolism, inflammation, and function.

PMID- 27692562
TI  - Rhein reverses Klotho repression via promoter demethylation and protects against
      kidney and bone injuries in mice with chronic kidney disease.
AB  - Rhein is an anthraquinone compound isolated from the medicinal plant rhubarb and
      mainly used in the clinical treatment of diabetic nephropathy. Rhein exhibits
      various renoprotective functions, but the underlying mechanisms are not fully
      determined. However, its renoprotective properties recapitulate the role of
      Klotho, a renal-specific antiaging protein critical for maintaining kidney
      homeostasis. Here we explored the connections between rhein renoprotection and
      Klotho in a mouse model of adenine-induced chronic kidney disease. In addition to
      being an impressive Klotho upregulator, rhein remarkably reversed renal Klotho
      deficiency in adenine-treated mice. This effect was associated with significant
      improvement in disturbed serum biochemistry, profibrogenic protein expression,
      and kidney and bone damage. Further investigation of the molecular basis of
      Klotho loss revealed that these kidneys displayed marked inductions of DNA
      methyltransferase DNMT1/DNMT3a and Klotho promoter hypermethylation, whereas
      rhein treatment effectively corrected these alterations. The renal protective
      effects of rhein were largely abolished when Klotho was knocked-down by RNA
      interferences, suggesting that rhein reversal of Klotho deficiency is essential
      for its renoprotective actions. Thus, our study clarifies how rhein regulation of
      Klotho expression contributes to its renoprotection and brings new insights into
      Klotho-targeted strategy for the treatment of kidney diseases of various
      etiologies.

PMID- 27692563
TI  - Low-dose hydralazine prevents fibrosis in a murine model of acute kidney injury
      to-chronic kidney disease progression.
AB  - Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are
      intrinsically tied syndromes. In this regard, the acutely injured kidney often
      does not achieve its full regenerative capacity and AKI directly transitions into
      progressive CKD associated with tubulointerstitial fibrosis. Underlying
      mechanisms of such AKI-to-CKD progression are still incompletely understood and
      specific therapeutic interventions are still elusive. Because epigenetic
      modifications play a role in maintaining tissue fibrosis, we used a murine model
      of ischemia-reperfusion injury to determine whether aberrant promoter methylation
      of RASAL1 contributes causally to the switch between physiological regeneration
      and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression. It is
      known that the antihypertensive drug hydralazine has demethylating activity, and
      that its optimum demethylating activity occurs at concentrations below blood
      pressure-lowering doses. Administration of low-dose hydralazine effectively
      induced expression of hydroxylase TET3, which catalyzed RASAL1 hydroxymethylation
      and subsequent RASAL1 promoter demethylation. Hydralazine-induced CpG promoter
      demethylation subsequently attenuated renal fibrosis and preserved excretory
      renal function independent of its blood pressure-lowering effects. In comparison,
      RASAL1 demethylation and inhibition of tubulointerstitial fibrosis was not
      detected upon administration of the angiotensin-converting enzyme inhibitor
      Ramipril in this model. Thus, RASAL1 promoter methylation and subsequent
      transcriptional RASAL1 suppression plays a causal role in AKI-to-CKD progression.

PMID- 27692564
TI  - Release of extracellular DNA influences renal ischemia reperfusion injury by
      platelet activation and formation of neutrophil extracellular traps.
AB  - Acute kidney injury is often the result of ischemia reperfusion injury, which
      leads to activation of coagulation and inflammation, resulting in necrosis of
      renal tubular epithelial cells. Platelets play a central role in coagulation and
      inflammatory processes, and it has been shown that platelet activation
      exacerbates acute kidney injury. However, the mechanism of platelet activation
      during ischemia reperfusion injury and how platelet activation leads to tissue
      injury are largely unknown. Here we found that renal ischemia reperfusion injury
      in mice leads to increased platelet activation in immediate proximity of necrotic
      cell casts. Furthermore, platelet inhibition by clopidogrel decreased cell
      necrosis and inflammation, indicating a link between platelet activation and
      renal tissue damage. Necrotic tubular epithelial cells were found to release
      extracellular DNA, which, in turn, activated platelets, leading to platelet
      granulocyte interaction and formation of neutrophil extracellular traps ex vivo.
      Renal ischemia reperfusion injury resulted in increased DNA-platelet and DNA
      platelet-granulocyte colocalization in tissue and elevated levels of circulating
      extracellular DNA and platelet factor 4 in mice. After renal ischemia reperfusion
      injury, neutrophil extracellular traps were formed within renal tissue, which
      decreased when mice were treated with the platelet inhibitor clopidogrel. Thus,
      during renal ischemia reperfusion injury, necrotic cell-derived DNA leads to
      platelet activation, platelet-granulocyte interaction, and subsequent neutrophil
      extracellular trap formation, leading to renal inflammation and further increase
      in tissue injury.

PMID- 27692565
TI  - HALT-D: A Phase II Evaluation of Crofelemer for the Prevention and Prophylaxis of
      Diarrhea in Patients With Breast Cancer on Pertuzumab-Based Regimens.
AB  - Approximately 40% to 80% of patients receiving pertuzumab-directed therapy for
      human epidermal growth factor receptor 2 (HER2)-positive breast cancer will
      develop chemotherapy-induced diarrhea (CID). Loperamide and octreotide are
      frequently used to treat CID after diarrhea occurs, but neither is used
      prophylactically or targets the underlying mechanism. Previous studies suggest
      blocking epidermal growth factor receptor may cause excess chloride secretion,
      resulting in diarrhea. Crofelemer is derived from the red latex of the Croton
      lechleri tree, blocks gastrointestinal cystic fibrosis transmembrane regulator
      and calcium-activated chloride channels, and is U.S. Food and Drug Administration
      approved for relief of diarrhea in HIV/AIDS patients on anti-retroviral therapy.
      Crofelemer is not systemically absorbed, has relatively few side effects, and
      presents a targeted approach at preventing CID in patients receiving pertuzumab
      based therapy. HALT-D (DiarrHeA Prevention and ProphyLaxis with Crofelemer in
      HER2-Positive Breast Cancer Patients Receiving Trastuzumab, Pertuzumab, and
      Docetaxel or Paclitaxel with or without Carboplatin, NCT02910219) is a phase II,
      randomized, open-label trial that aims to recruit 46 patients from 3 MedStar
      sites. Adults with HER2-positive breast cancer being treated with trastuzumab,
      pertuzumab, and docetaxel or paclitaxel (THP) or trastuzumab, pertuzumab,
      docetaxel, and carboplatin (TCHP) will be randomized to receive crofelemer or no
      medication for diarrhea prophylaxis. The primary endpoint is incidence of all
      grade diarrhea for >= 2 consecutive days during cycles 1 to 2 of THP or TCHP.
      Secondary endpoints include overall incidence, duration, and severity of
      diarrhea; time to onset of diarrhea; use of other anti-diarrheal medications;
      stool frequency and consistency; and quality of life. HALT-D will provide
      important information about the feasibility and tolerability of crofelemer in
      preventing diarrhea for patients receiving THP or TCHP.

PMID- 27692566
TI  - Clinical outcome of treatment with or without a final kissing balloon technique
      for bifurcation in-stent restenosis lesions.
AB  - BACKGROUND: The treatment strategy for in-stent restenosis (ISR) with bifurcation
      lesions has not been well explored. We examined the clinical outcomes between
      final kissing balloon technique (FKBT) after stent implantation and single-stent
      implantation without FKBT for bifurcation ISR lesions. METHODS: We identified 115
      consecutive ISR with bifurcation lesions among 108 patients who underwent drug
      eluting stent implantation. The patients were divided into the FKBT group (34
      patients, 35 lesions) and the non-FKBT group (74 patients, 80 lesions). RESULTS:
      Thrombolysis in myocardial infarction flow grade of side branch was significantly
      greater in the patients with FKBT than those without FKBT after coronary
      intervention (2.80+/-0.46 vs. 2.65+/-0.68, p=0.04), but this difference was
      attenuated and was no longer statistically significant at the time of follow-up
      (2.80+/-0.48 vs. 2.80+/-0.60, p=0.97). During a mean follow-up of 47.8+/-23.6
      months, there were no significant differences in the incidence of major adverse
      cardiac events (MACE). In multivariate analysis, estimated glomerular filtration
      rate (hazard ratio: 0.96, 95% confidence interval: 0.92-0.99, p=0.02) was an
      independent predictor of MACE. Contrast volume (170.71+/-47.17ml vs. 136.46+/
      55.56ml, p=0.002) and radiation dose (1.44+/-1.65Gy vs. 0.96+/-0.46Gy, p=0.02)
      were significantly higher in the FKBT group than in the non-FKBT group.
      CONCLUSIONS: Single-stent implantation without FKBT may be a sufficient treatment
      strategy for bifurcation ISR lesions.

PMID- 27692567
TI  - Prognostic impact of homocysteine levels and homocysteine thiolactonase activity
      on long-term clinical outcomes in patients undergoing percutaneous coronary
      intervention.
AB  - BACKGROUND: Numerous studies have reported the relationship between elevated
      homocysteine (Hcy) levels and the risk of coronary artery disease. However, there
      is insufficient information about the effects of Hcy levels on long-term clinical
      outcomes in patients with coronary artery disease undergoing percutaneous
      coronary intervention (PCI). METHODS: In the Juntendo-registry cohort from 2003
      to 2004, pre-procedural Hcy levels and Hcy thiolactonase activity (HTlase) were
      measured in 315 consecutive all-comer patients who underwent PCI for stable
      coronary artery disease or acute coronary syndrome (ACS). Receiver-operating
      characteristic (ROC) curves were created to assess the optimal cut-off values of
      Hcy and HTlase. Multivariable Cox proportional hazard regression analysis was
      used to identify the predictors of clinical outcome. The primary endpoint was all
      cause mortality. RESULTS: The patients' mean age was 66+/-9 years, and 82.5% were
      males. The median follow-up period was 10.5 years, and overall mortality was
      24.5% (73 deaths). On ROC analysis, the optimal cut-off values of Hcy and HTlase
      were 13.5MUmol/L and 230IU/L, respectively. Kaplan-Meier survival analysis showed
      associations of both higher Hcy levels and lower HTlase activity with worse
      prognosis (both log-rank p<0.001). On multivariate Cox proportional hazard
      regression analysis, higher Hcy was strongly associated with the primary outcome,
      and the adjusted hazard ratio was 3.3 (95% confidence interval, 1.8-5.6;
      p<0.001). CONCLUSIONS: Pre-procedural high Hcy levels and low HTlase activity
      were associated with worse long-term mortality in Japanese patients undergoing
      PCI. Moreover, Hcy levels are strongly predictive for mortality, independent of
      traditional risk factors. This may have implications for risk stratification and
      the therapeutic approach in this PCI era.

PMID- 27692568
TI  - Effect of over-2-year dual antiplatelet therapy on the rate of major adverse
      cardiac and cerebral events for everolimus-eluting stent implantation: The
      landmark analysis from Tokyo-MD PCI registry.
AB  - BACKGROUND: Long-term dual antiplatelet therapy (DAPT) for patients treated with
      coronary stents has been reported to be effective. However the effectiveness of
      long-term DAPT for everolimus-eluting stent (EES) implanted patients has been
      controversial. We assessed the major adverse cardiac and cerebral events (MACCE:
      a composite of death, myocardial infarction, or cerebral arterial disease) in
      patients free from MACCE during the first 2 years after EES implantation. METHODS
      AND RESULTS: A total of 1918 patients who underwent successful percutaneous
      coronary intervention (PCI) with EES at 22 centers in Japan in 2010-2011 were
      enrolled, and 742 patients were free from MACCE for 2 years. We divided these
      MACCE-free patients into two groups: those who received DAPT for >2 years (Over-2
      Year DAPT: n=591), and those who received DAPT for <=2 years (Under-2-Year DAPT:
      n=151). We performed the landmark analysis that began at 2 years and evaluated at
      3 years after PCI about the occurrence of MACCE, major bleeding, stent
      thrombosis, and restenosis between these groups, both with and without baseline
      adjustment by propensity score matching (n=145 in both groups). RESULTS: Fifty
      MACCE cases were reported (Over-2-Year DAPT, 38; Under-2-Year DAPT, 12), with no
      significant differences between the 2 groups (log-rank test, p=0.19). Even after
      baseline adjustment, there were no differences in MACCE occurrence (Over-2-Year
      DAPT, 8; Under-2-Year DAPT, 11, p=0.19); 15 cases of major bleeding, 5 of
      restenosis, and 2 of stent thrombosis were observed after 2-years' follow-up,
      with no statistical differences between the groups, although the event numbers
      were too low for comparison. CONCLUSION: Continuing DAPT for >2 years did not
      prevent MACCE in patients free from MACCE during initial 2 years after EES
      implantation. Few events of major bleeding, stent thrombosis, and restenosis were
      observed, with no statistical differences.

PMID- 27692569
TI  - Anatomic features of independent right posterior portal vein variants:
      Implications for left hepatic trisectionectomy.
AB  - BACKGROUND: No authors have reported on the anatomic features of the independent
      right posterior portal vein variant and its relevance to left hepatic
      trisectionectomy. The purpose of this study was to review vasculobiliary systems
      according to portal vein anatomy, to clarify the anatomic features of the right
      posterior portal vein variant, and to discuss its operative implications for left
      hepatic trisectionectomy. METHODS: In a radiologic study, the 3-dimensional
      anatomy of the portal vein, hepatic artery, and bile duct were studied in 200
      patients who underwent computed tomography. In a surgical study, medical records
      were retrospectively reviewed for 463 patients who underwent hepatectomy for
      perihilar cholangiocarcinoma. RESULTS: In the radiologic study, an independent
      right posterior portal vein variant was observed in 19 patients. The following
      observations were made in association with the portal vein variant: (1) a
      supraportal or combined type right posterior hepatic artery was never found; (2)
      an infraportal right posterior bile duct was observed at a significantly greater
      frequency than in patients with normal portal vein anatomy; and (3) the volume of
      the right posterior sector was significantly larger than in normal portal vein
      anatomy (37.4 +/- 6.1% vs 27.3 +/- 5.1%, P < .001). In the surgical study, the
      independent right posterior portal vein variant was observed in 41 (8.9%)
      patients. Of the 135 patients who underwent left hepatic trisectionectomy, 28
      (20.7%) had this portal vein variant. CONCLUSION: Independent right posterior
      portal vein variants exhibit anatomic features that are advantageous for
      performing left hepatic trisectionectomy.

PMID- 27692570
TI  - Tooth wear: A response to "Scratching the surface: A critique of Lucas et al.
      (2013)'s conclusion that phytoliths do not abrade enamel" [J. Hum. Evol. 74
      (2014) 130-133].

PMID- 27692571
TI  - The added value of a surveillance human biomonitoring program: The case of FLEHS
      in Flanders (Belgium).
AB  - Since 2002, the Flemish Government decided to carry out the Flemish Environment
      and Health Survey (FLEHS), an extended human biomonitoring (HBM) program, which
      is integrated in the environmental health policy. Through the FLEHS studies, a
      vast amount of data such as biomarkers of exposure and effect, exposure-effect
      associations, time trends and geographical differences, became available to the
      Flemish policy makers. In order to facilitate the policy interpretation, a phased
      action-plan was developed collaboratively by FLEHS researchers and policy makers.
      In this article we look back on more than 15 years of investments of the Flemish
      government in HBM and reflect on how this large scaled and challenging HBM
      initiative contributed to shaping the environmental health policy in Flanders. We
      used the FLEHS I (2002-2006) and II (2007-2011) results on persistent organic
      pollutants (POPs) and the resulting policy actions as an example to illustrate
      the added value of HBM for policy making. Policy measures for POPs, including
      source-related regulation (e.g. further optimization and tightening of existing
      Flemish legislation on open fires), investment in monitoring networks and
      communication and awareness campaigns, are presented and the added value for
      environmental health policy is discussed. We also reflect on how HBM can support
      science and innovation in the environmental monitoring context. Finally, we
      describe what society can gain from HBM in terms of opportunities for (1) feeding
      the political and societal debate, (2) stimulating community involvement and (3)
      empowering participants and citizens. All together, the gained insights and
      phased action plan showed that next to compliance with high scientific standards,
      results of the Flemish human biomonitoring campaign could be translated in
      targeted policy actions even for chemicals that have since long been regulated.

PMID- 27692572
TI  - Characterization of exposure in epidemiological studies on air pollution from
      biodegradable wastes: Misclassification and comparison of exposure assessment
      strategies.
AB  - The assignment of exposure is one of the main challenges faced by environmental
      epidemiologists. However, misclassification of exposures has not been explored in
      population epidemiological studies on air pollution from biodegradable wastes.
      The objective of this study was to investigate the use of different approaches
      for assessing exposure to air pollution from biodegradable wastes by analyzing
      (1) the misclassification of exposure that is committed by using these
      surrogates, (2) the existence of differential misclassification (3) the effects
      that misclassification may have on health effect estimates and the interpretation
      of epidemiological results, and (4) the ability of the exposure measures to
      predict health outcomes using 10-fold cross validation. Four different exposure
      assessment approaches were studied: ammonia concentrations at the residence
      (Metric I), distance to the closest source (Metric II), number of sources within
      certain distances from the residence (Metric IIIa,b) and location in a specific
      region (Metric IV). Exposure-response models based on Metric I provided the
      highest predictive ability (72.3%) and goodness-of-fit, followed by IV, III and
      II. When compared to Metric I, Metric IV yielded the best results for exposure
      misclassification analysis and interpretation of health effect estimates,
      followed by Metric IIIb, IIIa and II. The study showed that modelled NH3
      concentrations provide more accurate estimations of true exposure than distances
      based surrogates, and that distance-based surrogates (especially those based on
      distance to the closest point source) are imprecise methods to identify exposed
      populations, although they may be useful for initial studies.

PMID- 27692573
TI  - New specific and sensitive biomonitoring methods for chemicals of emerging health
      relevance.
AB  - In this publication the challenges to cope for the aim to obtain innovative
      biomonitoring methods in our laboratory are visualized for di(2
      propylheptyl)phthalate, 2-mercaptobenzothiazole, 3,5-di-tert-butyl-4
      hydroxytoluene, 4-nonylphenol, 4-tert-octylphenol, 3-(4
      methylbenzylidene)camphor, 4,4'-methylene diphenyl diisocyanate, and
      Hexabromocyclododecane. For these substances new specific markers were explored
      based on animal or human kinetic data with urine being the preferred matrix
      compared to blood. The determination of these markers was complex in all cases,
      because the sample preparation as well as the detection by high performance
      liquid chromatography, capillary gas chromatography coupled to tandem mass
      spectrometers or high resolution mass spectrometry should enable the lowest
      possible detection limit by use of minimal biological sample volumes. To get a
      first hint of a possible background level, the analytical methods were applied to
      urine samples of about 40 persons for each chemical. For Di(2
      propylheptyl)phthalate and 2-Mercaptobenzothiazole first results are presented
      from population biomonitoring.

PMID- 27692575
TI  - The impact of nutrition education on nutrition knowledge and adherence to the
      Mediterranean Diet in adolescent competitive swimmers.
AB  - OBJECTIVES: Nutrition education of adolescent competitive swimmers is under
      studied although their diet and nutrition knowledge are generally poor. This
      study aimed to assess the impact of nutrition education on nutrition knowledge
      and adherence to the Mediterranean Diet (MD) and explore the effect of parental
      education on the swimmers' MD adherence. DESIGN: A pre-post measurement
      interventional study was carried out. METHODS: A half-day nutrition education
      session was delivered for the swimmers and a separate session for their parents.
      At baseline and 6-weeks post-workshop, a short nutrition knowledge assessment of
      food sources of nutrients and the MD composition as well as adherence to the MD
      using the KIDMED Index were undertaken. The swimmers' parents also completed the
      KIDMED Index to evaluate the swimmers' diet. RESULTS: Thirty-four competitive
      swimmers (age: 15.2+/-1.5 yr, 23 males) and 22 of their parents participated in
      the study. There was an improvement in MD adherence with 47% having good
      adherence post-intervention vs 21% at baseline (p<0.01) and an increase in the
      KIDMED Index score (median [interquartile range]: 5.0 [4.0-7.0] vs 7.0 [7.0-9.0];
      p<0.01)). There was also an increase in the swimmers' nutrition knowledge
      assessment score (median [IQR]: 7.0 [5.0-8.0] vs 7.0 [6.0-8.0], p<0.05)), and a
      trend for a lower score post-intervention in swimmers whose parents did not
      participate compared to those whose parents participated (6.0 [6.0-7.8] vs 7.0
      [7.0-8.0], p=0.063). CONCLUSIONS: The intervention improved adherence to the MD
      and increased nutrition knowledge. The findings support parental participation in
      nutrition education.

PMID- 27692574
TI  - [Epigenetics and obesity].
AB  - Current evidence supports the notion that exposure to various environmental
      conditions in early life may induce permanent changes in the epigenome that
      persist throughout the life-course. This article focuses on early changes
      associated with obesity in adult life. A review is presented on the factors that
      induce changes in whole genome (DNA) methylation in early life that are
      associated with adult onset obesity and related disorders. In contrast, reversal
      of epigenetic changes associated with weight loss in obese subjects has not been
      demonstrated. This contrasts with well-established associations found between
      obesity related DNA methylation patterns at birth and adult onset obesity and
      diabetes. Epigenetic markers may serve to screen indivuals at risk for obesity
      and assess the effects of interventions in early life that may delay or prevent
      obesity in early life. This might contribute to lower the obesity-related burden
      of death and disability at the population level. The available evidence indicates
      that epigenetic marks are in fact modifiable, based on modifications in the
      intrauterine environment and changes in food intake, physical activity and
      dietary patterns patterns during pregnancy and early years of adult life. This
      offers the opportunity to intervene before conception, during pregnancy, infancy,
      childhood, and also in later life. There must be documentation on the best
      preventive actions in terms of diet and physical activity that will modify or
      revert the adverse epigenetic markers, thus preventing obesity and diabetes in
      suceptible individuals and populations.

PMID- 27692576
TI  - Assessing muscle strength for the purpose of classification in Paralympic sport:
      A review and recommendations.
AB  - OBJECTIVES: Classification in Paralympic Sport aims to minimize the impact of 10
      eligible types of impairment on the outcome of competition. Methods for assessing
      the extent to which a given body structure or function has been impaired are
      required, but are challenging because it is not possible to directly measure an
      absence or loss. Rather, impairment must be inferred by measurement of extant
      body structures or functions. METHODS: This manuscript reviews the literature
      concerning the assessment of strength with the aim of identifying and describing
      the most appropriate method for inferring strength impairment in para-athletes.
      RESULTS: It is posited that the most appropriate voluntary strength assessment
      method for inferring strength loss in para-athletes will be multi-joint,
      isometric tests performed at joint angles that facilitate maximum force
      production. CONCLUSIONS: Evidence suggests such methods will permit development
      of tests that are specific to a variety of para-sports and which are reliable,
      ratio-scaled, and resistant to training. Future research should: develop sport
      specific tests which are suitable for assessment of athletes with strength
      impairments of variable severity and distribution; and scientifically evaluate
      the extent to which such tests permit strength impairment to be validly inferred,
      including specific evaluation of the extent to which such measures respond to
      athletic training.

PMID- 27692577
TI  - Surface properties of polyetheretherketone after different laboratory and
      chairside polishing protocols.
AB  - STATEMENT OF PROBLEM: Polyetheretherketone (PEEK) can be used as a framework
      material for fixed dental prostheses. However, information about laboratory and
      chairside polishing methods is still scarce. PURPOSE: The purpose of this in
      vitro study was to determine the effects of laboratory and chairside polishing
      methods on the surface roughness (SR) and surface free energy (SFE) of PEEK, an
      autopolymerizing poly(methyl methacrylate), and a veneering composite resin.
      MATERIAL AND METHODS: For each of the 3 materials, 80 specimens were prepared
      (N=240) and divided into 7 polishing groups and 1 control group (n=10). The 7
      groups were split into 4 laboratory protocols: polishing paste (Abraso), a second
      polishing paste (Opal L), silicone polisher (Ceragum), and diamond grinder
      (Diagen-Turbo grinder). The other 3 groups were chairside protocols: rainbow
      technique (Super-Snap kit), polishing paste (Prisma gloss), and a polishing
      system (Enhance finishing). Machine polishing with SiC P4000 served as the
      control treatment. The protocols' average SRs and SFEs were measured, and their
      surface topographies were evaluated with scanning electron microscopy (SEM). The
      logarithmically transformed data were analyzed using covariance analysis, 2-way
      and 1-way ANOVA, and partial correlation (alpha=.05). RESULTS: The polishing
      protocol exerted the highest influence on SR and SFE values (P<.001; SR: partial
      eta squared etaP2=.970; SFE: etaP2=.450), followed by material group (P<.001, SR:
      etaP2=.319; SFE: etaP2=.429). The interaction effect of the binary combinations
      of the 2 independent parameters (polishing protocol and material group) was also
      significant (P<.001, SR: etaP2=.681; SFE: etaP2=.365). CONCLUSIONS: Chairside
      methods presented lower SR values than laboratory methods, and specimens polished
      using the 2-body mode showed higher SR than did specimens polished using the 3
      body mode.

PMID- 27692578
TI  - Patient-centered and clinical outcomes of mandibular overdentures retained with
      the locator system: A prospective observational study.
AB  - STATEMENT OF PROBLEM: Whether clinical or demographic variables affect the
      perception of treatment in terms of quality of life and satisfaction is unknown.
      PURPOSE: The purpose of this prospective study was to make an evidence-based
      assessment of the treatment outcomes (patient- and clinically based) of locator
      retained mandibular overdentures. MATERIAL AND METHODS: This prospective
      observational study assessed patients with edentulism who had worn mandibular
      overdentures supported by 2 implants and retained by the locator system for at
      least 1 year of functional life (N=80). Medical histories were reviewed, and
      patients underwent oral examinations. Prosthetic clinical outcomes and patient
      well-being were registered using the Oral Health Impact Profile 20 (OHIP-20) and
      Oral Satisfaction Scale (OSS). RESULTS: Patient well-being scored an overall OHIP
      20 score of 19.0 +/-14.0 of 80 (the higher the score, the greater the impact and
      the worse the oral health-related quality of life); overall oral satisfaction was
      8.3 +/-1.7 of 10. Women suffered greater social impact (0.8 +/-1.0) and
      disability (0.4 +/-0.8) than men (0.4 +/-0.7 versus 0.2 +/-0.4, respectively).
      Impact on well-being was inversely proportional to both patient age and the age
      of the prosthesis (r=-0.25; P<.01). Implants had been placed on average 73.6 +/
      39.2 months previously, showing a survival rate of 82.5%. Most of the
      overdentures had been functioning for over 60 months. Relining (46.3%),
      readjustments (82.5%), and changes of nylon retention (1.5 +/-1.8 per patient
      over 60 months of use) devices negatively influenced well-being. CONCLUSIONS:
      Mandibular overdentures produced good results with regard to quality of life and
      oral satisfaction, but attention should be paid to factors affecting clinical
      outcomes and patient well-being.

PMID- 27692579
TI  - In vivo study of the effectiveness of quantitative percussion diagnostics as an
      indicator of the level of structural pathology of teeth after restoration.
AB  - STATEMENT OF PROBLEM: Conventional diagnostic aids based upon imagery and patient
      symptoms do not indicate whether restorative treatments have eliminated
      structural pathology. PURPOSE: The purpose of this clinical study was to evaluate
      quantitative percussion diagnostics (QPD), a mechanics-based methodology that
      tests the structural integrity of teeth noninvasively. The study hypothesis was
      that QPD would provide knowledge of the structural instability of teeth after
      restorative work. MATERIAL AND METHODS: Eight participants with 60 sites needing
      restoration were enrolled in an IRB-approved clinical study. Each participant was
      examined comprehensively, including QPD testing. Each site was disassembled and
      microscopically video documented, and the results were recorded on a defect
      assessment sheet. A predictive model was developed for the pathology rating based
      on normalized fit error (NFE) values using data from the before treatment phase
      of the study published previously. Each restored site was then tested using QPD.
      The mean change in NFE values after restoration was evaluated by the pathology
      rating before treatment. The model was then used to predictively classify the
      rating after restoration based on the NFE values after treatment. The diagnostic
      potential of the rating was explored as a marker for risk of pathology after
      restoration. RESULTS: After restoration, 51 of the 60 sites fell below an NFE of
      0.04, representing a greatly stabilized tooth site sample group. Several sites
      remained in the high-risk category and some increased in pathologic
      micromovement. Two models were used to determine severity with indicative cutoff
      points to group sites with similar values. CONCLUSIONS: The data support the
      hypothesis that QPD can indicate a revised level of structural instability of
      teeth after restoration.

PMID- 27692581
TI  - Precision prosthodontics.

PMID- 27692580
TI  - Implant-supported maxillary denture retained by a telescopic abutment system: A
      clinical report.
AB  - An implant-supported fixed dental prosthesis is one of the treatment options for
      an individual with a completely edentulous maxilla. However, a screw-retained or
      cemented prosthesis can make oral hygiene difficult, especially for patients with
      a history of periodontal disease or disabilities. Compared with maxillary fixed
      dental prostheses, implant-supported overdentures offer similar retention and
      function and facilitate esthetics, phonetics, and hygiene. This report describes
      the prosthetic rehabilitation of a patient with an edentulous maxilla and a
      severe maxillomandibular discrepancy that involved the use of a novel
      prefabricated telescopic system to retain an implant-supported removable dental
      prosthesis.

PMID- 27692582
TI  - Effect of silane contamination on dentin bond strength.
AB  - STATEMENT OF PROBLEM: Intraoral repair of porcelain or other silica-based
      ceramics typically requires the use of silane in the repair protocol. Some
      porcelain intraoral repairs also involve bonding to exposed or involved tooth
      tissues including dentin. A study is needed to evaluate whether the cross
      contamination of dentin with silane affects bond strength to this tissue.
      PURPOSE: The purpose of this in vitro study was to investigate the effect of
      silane cross-contamination on dentin bond strength. MATERIAL AND METHODS: Flat
      surfaces of human dentin specimens were created, followed by wet polishing with
      320-grit silicon carbide paper. The dentin specimens were divided into 4 groups:
      group SE (All-Bond Universal Adhesive used in self-etching mode); group SiSE
      (silane applied to dentin followed by All-Bond Universal Adhesive used in self
      etching mode); group ER (All-Bond Universal Adhesive used in total-etch (etch-and
      rinse) mode); and group ERSi (Etch and rinse and silane applied to dentin
      followed by All-Bond Universal Adhesive). The dentin specimens were treated with
      a universal adhesive (All-Bond Universal) and bonded with a composite resin,
      using an Ultradent jig mold. Shear bond strength (n=10) was measured after 24
      hours of water storage at 37 degrees C. After the shear bond strength test, the
      dentin sides of fractured specimens in each group were examined with a
      stereomicroscope at *15 magnification to determine failure modes. Data were
      statistically analyzed by 2-way and a 1-way ANOVA followed by post hoc Tukey
      honest significant difference test (alpha=.05). Scanning electron microscopy
      examination was used to evaluate the dentin surface morphology before and after
      bonding. RESULTS: The shear bond strength of composite resin to dentin was not
      affected adversely when the dentin was contaminated with silane prior to using
      All-Bond Universal in the self-etch or total- etch (phosphoric acid) mode. SE,
      30.3 +/-3.8 MPa; SiSE, 32.9 +/-3.9 MPa; ER, 34.9 +/-3.1 MPa; ERSi: 35.2 +/-4.9
      MPa (P>.05) CONCLUSIONS: Under the conditions of this study, cross-contamination
      of dentin with silane before the use of All-Bond Universal in the self-etch or
      total-etch with phosphoric acid mode did not adversely affect composite resin
      bond strength to dentin.

PMID- 27692583
TI  - Using modified polyetheretherketone (PEEK) as an alternative material for
      endocrown restorations: A short-term clinical report.
AB  - A modified polyetheretherketone (PEEK) framework material veneered with indirect
      light-polymerized composite resin was used as an alternative material for the
      fabrication of an endocrown restoration for an extensively damaged molar. The
      elastic modulus of the polyetheretherketone framework (4 GPa) veneered with
      indirect composite resin could dampen the occlusal forces protecting tooth
      structures better than ceramic materials. This is important in the restoration of
      extensively damaged molars with weak roots. Long-term clinical evidence is
      required before recommending the application as a substitute material.

PMID- 27692584
TI  - Internal fit of single crowns produced by CAD-CAM and lost-wax metal casting
      technique assessed by the triple-scan protocol.
AB  - STATEMENT OF PROBLEM: Whether single crowns produced by computer-aided design and
      computer-aided manufacturing (CAD-CAM) have an internal fit comparable to crowns
      made by lost-wax metal casting technique is unknown. PURPOSE: The purpose of this
      in vitro study was to compare the internal fit of single crowns produced with the
      lost-wax and metal casting technique with that of single crowns produced with the
      CAD-CAM technique. MATERIAL AND METHODS: The internal fit of 5 groups of single
      crowns produced with the CAD-CAM technique was compared with that of single
      crowns produced in cobalt-chromium with the conventional lost-wax and metal
      casting technique. Comparison was performed using the triple-scan protocol; scans
      of the master model, the crown on the master model, and the intaglio of the crown
      were superimposed and analyzed with computer software. The 5 groups were milled
      presintered zirconia, milled hot isostatic pressed zirconia, milled lithium
      disilicate, milled cobalt-chromium, and laser-sintered cobalt-chromium. RESULTS:
      The cement space in both the mesiodistal and buccopalatal directions was
      statistically smaller (P<.05) for crowns made by the conventional lost-wax and
      metal casting technique compared with that of crowns produced by the CAD-CAM
      technique. CONCLUSIONS: Single crowns made using the conventional lost-wax and
      metal casting technique have better internal fit than crowns produced using the
      CAD-CAM technique.

PMID- 27692585
TI  - A new 3D center of mass control approach for FES-assisted standing: First
      experimental evaluation with a humanoid robot.
AB  - This paper proposes a new control framework to restore the coordination between
      upper (functional) and lower (paralyzed) limbs in the context of functional
      electrical stimulation in completely paraplegic individuals. A kinematic
      decoupling between the lower and upper limbs controls the 3D whole-body center of
      mass location and the relative foot positions by acting only on the lower-limb
      joints. The upper limbs are free to move under voluntary control, and are seen as
      a perturbation for the lower limbs. An experimental validation of this paradigm
      using a humanoid robot demonstrates the real-time applicability and robustness of
      the method. Different scenarios mimicking the motion of a healthy subject are
      investigated. The proposed method can maintain bipedal balance and track the
      desired center of mass trajectories under movement disturbances of the upper
      limbs with an error inferior to 0.01 m under any conditions.

PMID- 27692586
TI  - Australian general practitioners' views regarding providing nutrition care:
      results of a national survey.
AB  - BACKGROUND: The prevalence of chronic disease is considerable, and dietary
      behaviours influence the progression of many chronic diseases. Practice
      guidelines recommend that general practitioners (GPs) promote healthy dietary
      behaviours in relevant consultations with patients in order to improve health
      outcomes at a population level. OBJECTIVE: To describe GPs' perceived interest,
      confidence and barriers to support patients to have a healthy diet. METHOD: A 24
      item online and written survey was distributed in a national weekly newsletter to
      GPs in Australia. Results were descriptively analysed and investigated for
      associations with GPs' demographic characteristics. RESULTS: A total of 322 GPs
      responded to the survey. Nearly all (n = 295, 91.6%) were interested in
      supporting patients to eat well, and most (n = 231, 71.7%) reported moderately
      high confidence for providing nutrition care with clear public health messages
      for conditions, such as cardiovascular disease. Many GPs (n = 170, 52.8%) cited
      lack of time as the biggest barrier to providing nutrition care, and the
      overwhelming majority (n = 289, 89.8%) were interested in receiving additional
      education and training to enhance their nutrition knowledge and skills.
      DISCUSSION: Many GPs are interested in nutrition and would benefit from
      educational programmes that improve their competence to provide nutrition care.
      Professional development opportunities should focus on the identification of
      nutritional risk and the promotion of healthy dietary behaviours within the time
      constraints of a standard consultation.

PMID- 27692587
TI  - Arthroscopic anatomical reconstruction of the lateral ankle ligaments: A
      technical simplification.
AB  - Anatomical reconstruction of the lateral ankle ligaments has become a pivotal
      component of the treatment strategy for chronic ankle instability. The recently
      described arthroscopic version of this procedure is indispensable to ensure that
      concomitant lesions are appropriately managed, yet remains technically demanding.
      Here, we describe a simplified variant involving percutaneous creation of the
      calcaneal tunnel for the distal attachment of the calcaneo-fibular ligament. The
      rationale for this technical stratagem was provided by a preliminary cadaver
      study that demonstrated a correlation between the lateral malleolus and the
      distal footprint of the calcaneo-fibular ligament. The main objectives are
      simplification of the operative technique and decreased injury to tissues whose
      function is crucial to the recovery of proprioception.

PMID- 27692588
TI  - Use of a Machine-learning Method for Predicting Highly Cited Articles Within
      General Radiology Journals.
AB  - RATIONALE AND OBJECTIVES: This study aimed to assess the performance of a text
      classification machine-learning model in predicting highly cited articles within
      the recent radiological literature and to identify the model's most influential
      article features. MATERIALS AND METHODS: We downloaded from PubMed the title,
      abstract, and medical subject heading terms for 10,065 articles published in 25
      general radiology journals in 2012 and 2013. Three machine-learning models were
      applied to predict the top 10% of included articles in terms of the number of
      citations to the article in 2014 (reflecting the 2-year time window in
      conventional impact factor calculations). The model having the highest area under
      the curve was selected to derive a list of article features (words) predicting
      high citation volume, which was iteratively reduced to identify the smallest
      possible core feature list maintaining predictive power. Overall themes were
      qualitatively assigned to the core features. RESULTS: The regularized logistic
      regression (Bayesian binary regression) model had highest performance, achieving
      an area under the curve of 0.814 in predicting articles in the top 10% of
      citation volume. We reduced the initial 14,083 features to 210 features that
      maintain predictivity. These features corresponded with topics relating to
      various imaging techniques (eg, diffusion-weighted magnetic resonance imaging,
      hyperpolarized magnetic resonance imaging, dual-energy computed tomography,
      computed tomography reconstruction algorithms, tomosynthesis, elastography, and
      computer-aided diagnosis), particular pathologies (prostate cancer; thyroid
      nodules; hepatic adenoma, hepatocellular carcinoma, non-alcoholic fatty liver
      disease), and other topics (radiation dose, electroporation, education, general
      oncology, gadolinium, statistics). CONCLUSIONS: Machine learning can be
      successfully applied to create specific feature-based models for predicting
      articles likely to achieve high influence within the radiological literature.

PMID- 27692589
TI  - Associations Between Academic Rank and Advanced Bibliometric Indices Among United
      States Academic Radiologists.
AB  - RATIONALE AND OBJECTIVES: This study aimed to evaluate associations between
      traditional and advanced bibliometric indices with academic rank for radiologists
      in the United States. METHODS: Faculty web pages were searched to classify 538
      members of the Association of University Radiologists as assistant (n = 212),
      associate (n = 128), or full (n = 198) professors. Radiologists' publication and
      citation records were extracted from Scopus to compute the following indices:
      publication count, citation count, h-index, i-10 index, hc-index, m-quotient, e
      index, and g-index. Analysis of variance, multivariable logistic regression, and
      receiver operating characteristic curve analysis were performed. RESULTS: All
      indices were significantly different among the three groups (P <=.001),
      progressively increasing with increasing rank (eg, mean publication count of 17,
      41, and 128 among assistant, associate, and full professors, respectively; mean
      citation count of 205, 687, and 3622, respectively; mean h-index of 5, 11, and
      27, respectively). At multivariable analysis, the h-index (reflecting
      publications and citations) was a strong significant independent positive
      predictor of associate (beta=+0.32, P <.001) or full professor (beta=+0.26, P
      <.001) status, whereas the m-quotient (adjusted h-index that is greater for more
      rapid publication) was a strong significant independent negative predictor of
      associate (beta=-1.87, P = .009) or full professor (beta =-4.97, P <.001) status.
      The models exhibited moderate goodness-of-fit (r2 = 0.534-0.655; P <.001). The
      model for predicting at least associate professor achieved area under the curve
      0.876 (sensitivity 74.6%, specificity 88.8%). The model for predicting full
      professor achieved area under the curve 0.925 (sensitivity 85.5%, specificity
      86.1%). CONCLUSION: When controlling for the h-index, more rapid publication, as
      indicated by the m-quotient, was negatively associated with radiologists'
      academic rank, indicating the additional influence of career duration in
      promotions decisions.

PMID- 27692590
TI  - Regional and network relationship in the intracranial EEG second spectrum.
AB  - OBJECTIVE: We examined low-frequency amplitude modulations of band power time
      series, i.e. the second spectrum, of the intracranial EEG (icEEG) for evidence of
      support for spatial relationships between different parts of the brain and within
      the default mode network (DMN). METHODS: We estimated magnitude-squared coherence
      (MSC) of the running power in the delta, theta, alpha, beta, and gamma frequency
      bands for one-hour background icEEG epochs recorded from 9 patients. We isolated
      two test areas within the DMN and one control area outside it. We tested if the
      relationship between DMN areas was stronger than the relationship between each of
      these areas and the control location, and between all intrahemispheric contact
      pairs with similar intercontact distance. RESULTS: We observed very low values of
      second spectrum relationship between different parts of the brain, except at very
      short distances. These relationships are strongest in the delta band and decrease
      with increasing frequency, with gamma band relationships being the weakest. Our
      DMN-specific analysis showed no enhanced connectivity in the second spectrum in
      DMN locations in any frequency band. CONCLUSIONS: Though we observed
      significantly nonzero relationships in lower frequency bands, second spectrum
      relationships are consistently very low across the entire brain in every
      frequency band. SIGNIFICANCE: This study suggests a lack of support for the DMN
      in the icEEG second spectrum.

PMID- 27692591
TI  - Comment on: Lipocalin-type prostaglandin D2 synthase modulates the beneficial
      metabolic effects of vertical sleeve gastrectomy.

PMID- 27692592
TI  - Meta-Analysis of Association Between Mediastinal Radiotherapy and Long-Term Heart
      Failure.
AB  - This investigation sought to identify and quantify any increased risk of long
      term heart failure (HF) after thoracic radiotherapy (RT) for cancer and identify
      any population covariates that corresponded with increased risk. Electronic
      databases were systematically searched for studies reporting relative risk, odds
      ratio, and hazard ratio (HR) for symptomatic HF more than 5 years after RT
      administration. Clinical characteristics, study design, univariable effect sizes,
      and associated 95% CIs were extracted. Univariable effect size was pooled and
      computed in a meta-analysis using random-effects model weighted by inverse
      variance. Six studies (45,669 patients) with weighted median follow-up duration
      of 13.9 years were included, each data-linkage study that reported HRs for HF.
      Pooled HR for long-term HF was significant (HR 1.83 [1.09 to 3.08], p = 0.022),
      with significant between-study heterogeneity (Q 43.38, df = 5, p <0.001, I2
      88.47%). Statistical significance was lost when excluding studies of malignancies
      other than breast cancer or hematological malignancies and excluding studies with
      Newcastle-Ottawa scores <8, but the direction of effect and magnitude remained
      approximately the same. Subgroup and meta-regression analyses demonstrated that
      study differences in age at time of RT administration and duration of follow-up
      explained approximately 80% of observed heterogeneity. Earlier publication date
      was associated with increased HF risk. Other variables, including female
      proportion, proportion of adjuvant chemotherapy use, and sample size did not
      significantly impact the conclusions. In conclusion, RT approximately doubled the
      long-term risk of HF. This finding was associated with younger age at time of RT
      and longer follow-up duration, which explained approximately 80% of interstudy
      heterogeneity.

PMID- 27692593
TI  - Long-Term Follow-Up of Patients With Previous Coronary Artery Bypass Grafting
      Undergoing Percutaneous Coronary Intervention for Chronic Total Occlusion.
AB  - Successful revascularization of chronic total occlusions (CTOs) has been
      associated with clinical benefit. Data on outcomes in patients with previous
      coronary artery bypass grafting (CABG) undergoing percutaneous coronary
      intervention (PCI) for CTO, however, are scarce. A total of 2,002 consecutive
      patients undergoing PCI for CTO from January 2005 to December 2013 were divided
      into patients with and without previous CABG, and outcomes were retrospectively
      assessed. The primary outcome measure was all-cause mortality. Median follow-up
      was 2.6 years (interquartile range 1.1 to 3.1). A total of 292 patients (15%) had
      previous CABG; they were older and had a greater prevalence of comorbidities.
      Procedural success was achieved in 75% and 84% of patients in the previous CABG
      and the non-CABG groups (p <0.001), respectively. All-cause mortality was 16% and
      11% in the previous CABG and the non-CABG groups (p = 0.002), and differences
      were mitigated after adjustment for baseline characteristics (adjusted hazard
      ratio [HR] 1.22, 95% confidence interval [CI] 0.86 to 1.74, p = 0.27). All-cause
      death was significantly reduced in patients with procedural success, both in the
      previous CABG (11% vs 32%, adjusted HR 0.43, 95% CI 0.24 to 0.77, p = 0.005) and
      the non-CABG groups (10% vs 20%, adjusted HR 0.63, 95% CI 0.45 to 0.86, p =
      0.004), with similar mortality benefits associated with successful
      revascularization in both groups (interaction p = 0.24). In conclusion, the
      relative survival benefit of successful recanalization of CTO is independent of
      previous CABG. However, owing to a greater baseline risk, the absolute survival
      benefit of successful CTO procedures is more pronounced in patients with previous
      CABG than in non-CABG patients.

PMID- 27692594
TI  - Meta-Analysis of Randomized Trials on the Efficacy and Safety of Angiotensin
      Converting Enzyme Inhibitors in Patients >=65 Years of Age.
AB  - The comparative efficacy and safety of angiotensin-converting enzyme inhibitors
      (ACEIs) with other agents in patients >=65 years of age with cardiovascular
      diseases or at-risk are unknown. Electronic databases were systematically
      searched to identify all randomized controlled trials that compared ACEIs with
      control (placebo or active) and reported long-term cardiovascular outcomes. We
      required the mean age of patients in the studies to be >=65 years. Random-effects
      model was used to pool study results. Sixteen trials with 104,321 patients and a
      mean follow-up of 2.9 years were included. Compared with placebo, ACEIs
      significantly reduced all outcomes except stroke. Compared with active controls,
      ACEIs had similar effect on all-cause mortality (relative risk [RR] 0.99, 95%
      confidence interval [CI] 0.95 to 1.03), cardiovascular mortality (RR 0.99, 95% CI
      0.93 to 1.04), heart failure (RR 0.97, 95% CI 0.91 to 1.03), myocardial
      infarction (RR 0.94, 95% CI 0.88 to 1.00), and stroke (RR 1.07, 95% CI 0.99 to
      1.15). ACEIs were associated with an increased risk of angioedema (RR 2.79, 95%
      CI 1.05 to 7.42), whereas risk for hypotension and renal insufficiency was
      similar compared with active controls. Meta-regression analysis showed that the
      effect of ACEIs on outcomes remained consistent with age increasing >=65 years.
      Sensitivity analysis excluding trials comparing ACEIs with angiotensin receptor
      blockers and heart failure trials yielded similar results, except for reduction
      in myocardial infarction. In conclusion, the efficacy of ACEIs was similar to
      active controls for mortality outcomes. Compared with placebo, there was evidence
      for reduction in cardiovascular outcomes; however, ACEIs failed to prevent stroke
      and increased the risk of angioedema, hypotension, and renal failure.

PMID- 27692596
TI  - Stop Blowing Smoke on Cigarettes as a Cause for Periodontitis.

PMID- 27692595
TI  - Local Versus General Anesthesia in Transcatheter Aortic Valve Replacement.
AB  - Transcatheter aortic valve replacement (TAVR) is conventionally performed under
      general anesthesia (GA) allowing intraoperative transoesophageal echocardiogram
      imaging. We present our experience in patients having the procedure under local
      anesthesia (LA), who were subsequently transferred to a low dependency unit
      postprocedure, to assess safety and length of hospital stay. We retrospectively
      assessed all the transfemoral TAVR procedures conducted at our center from
      January 03, 2011. Of 216 patients, 145 had the procedure under GA and 71 under
      LA. Both groups were similar with respect to age, co-morbidities, Euro Score, and
      the severity of the aortic stenosis. The procedure time was significantly shorter
      in the LA group measured from time in room to skin closure (108 vs 143 minutes, p
      <0.001). Skin open to skin closure time were the same in both groups (78 vs 79.4
      minutes, p = 0.57). There was no difference in 30 days: aortic regurgitation >
      mild (2.1% in GA and 2.8% in LA, p = 0.67), need for permanent pacing (3.4% in GA
      and 1.4% in LA, p = 0.32), and disabling cerebrovascular accidents (1.4% and
      1.4%, p = 1.0). The 30-day survival was not significantly different (95.9% in GA
      and 100% in LA, p = 0.17), whereas the median number of days in hospital was
      shorter in the LA group (4 in GA and 2 in LA, p <0.001). No emergency conversions
      to GA were performed in the LA group and only 1 patient needed admission to a
      high dependency (HD) unit. In conclusion, performing a TAVR under LA is at least
      as safe as GA. In addition, there is a reduced procedural time and length of
      hospital stay. LA is a safe and cost-effective alternative to GA and patients can
      be safely transferred to a low dependency unit.

PMID- 27692598
TI  - Reply.

PMID- 27692597
TI  - Usefulness of Serial N-terminal Pro-B-type Natriuretic Peptide Measurements to
      Predict Cardiac Death in Acute and Chronic Dilated Cardiomyopathy in Children.
AB  - N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor
      of outcome in adults with heart failure. In children with heart failure secondary
      to dilated cardiomyopathy (DC) markers that reliably predict disease progression
      and outcome during follow-up are scarce. We investigated whether serial NT-proBNP
      measurements were predictive for outcome in children with DC. All available NT
      proBNP measurements in children with DC were analyzed. Linear mixed-effect models
      and Cox regression were used to analyze the predictive value of NT-proBNP on the
      end point of cardiac death (death, heart transplantation, or mechanical
      circulatory support). During 7 years, 115 patients were included. At diagnosis,
      median NT-proBNP was high and not predictive for outcome. At any time during
      follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the
      first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001).
      Furthermore, at any time, the slope of log10(NT-proBNP) was significantly
      predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30
      days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days
      after diagnosis, NT-proBNP >=7,990 pg/ml showed a 1- and 2-year event-free
      survival of 79% and 71% and >1 year after diagnosis NT-proBNP >=924 pg/ml showed
      a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds
      event-free survival was 100%. In non-IDC, these thresholds were not predictive
      for outcome. In conclusion, NT-proBNP at any time during follow-up and its change
      over time were significantly predictive for the risk of cardiac death in children
      with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml
      identified a subgroup with a poor outcome.

PMID- 27692599
TI  - Reproductive outcome in European and Middle Eastern/North African patients.
AB  - The aim of this retrospective cohort study was to assess differences in
      infertility-related baseline characteristics and IVF outcome between European and
      Middle Eastern/North African (MENA) patients. Of 2703 patients undergoing their
      first IVF cycle, 2485 were Caucasian of European descent and 218 originated from
      the MENA region. MENA patients were significantly younger (30.6 versus 34.0
      years, P < 0.001), less likely smokers, with higher body mass indexes.
      Infertility duration was longer in MENA patients (P < 0.001), their male partners
      were younger (P < 0.001) and smoked more often than European male patients (P =
      0.005). Male factor infertility (P = 0.017) and polycystic ovary syndrome (PCOS;
      P = 0.032) was more prevalent in MENA patients, showed significantly higher basal
      FSH concentrations (P = 0.012) and significantly fewer oocytes retrieved (RR
      0.83, 95% CI 0.74-0.93, P = 0.001). Clinical pregnancy rates were comparable
      (22.4% [European] versus 22.9% [MENA]). Fewer MENA patients had surplus embryos
      cryopreserved (OR 0.41, 95% CI 0.22-0.76, P = 0.004). Despite younger age and
      higher prevalence of PCOS, MENA patients had significantly lower oocyte yields
      than their European counterparts (P = 0.001). These findings suggest a more rapid
      decline in ovarian function in women of MENA descent.

PMID- 27692600
TI  - Maternal serum markers in predicting successful outcome in expectant management
      of missed miscarriage.
AB  - The aim of this study was to evaluate the use of biological serum markers,
      available routinely in most hospital clinical laboratories, in predicting
      successful outcomes of expectant management in women presenting with a missed
      miscarriage. This is a single centre observational prospective study over a 16
      month period. Among the 490 women who consented to the study protocol, 83
      presented with missed miscarriage during the first trimester of pregnancy and
      opted for expectant management. The mean gestation sac diameter and volume of the
      gestation sac were recorded during ultrasound examination. Maternal serum samples
      were obtained in each case and assayed for human chorionic gonadotrophin,
      progesterone, pregnancy associated plasma protein A (PAPP-A) and high-sensitivity
      C-reactive protein using commercial assays. When examined individually, maternal
      age (P = 0.01), progesterone (P = 0.03) and PAPP-A (P = 0.02) were all
      significantly associated with successful expectant management. Increased maternal
      age was associated with an increased chance of success with the odds of success
      increased by around 75% for a 5-year increase in age. Higher values of
      progesterone and PAPP-A were associated with a reduced chance of successful
      management. Low maternal serum progesterone concentration was the strongest
      parameter associated with a successful spontaneous completion of miscarriage.

PMID- 27692601
TI  - Deficient expression of JMJD1A histone demethylase in patients with round
      spermatid maturation arrest.
AB  - JMJD1A (jumonji domain-containing 1A), a known histone H3K9 demethylase, has been
      identified as a critical epigenetic regulator in male germ cells, activating the
      sperm chromatin-packaging genes encoding protamines (PRM) and transition proteins
      (TNP) required for spermatid elongation and condensation. This research
      investigated the expression pattern of JMJD1A protein in testicular biopsies of
      79 infertile men who had undergone testicular sperm extraction. Samples were
      classified into obstructive azoospermia (OA, n = 26), round spermatid maturation
      arrest (SMA, n = 29) and Sertoli cell only syndrome (SCOS, n = 24). Experiments
      including the detection of mRNA and protein expressions of JMJD1A revealed a
      severe decrease of JMJD1A/JMJD1A in samples with SMA and SCOS compared with
      samples with OA (P < 0.005, Kruskal-Wallis test). Additional experiments,
      including incorporation of JMJD1A on the promoter regions of TNP and PRM genes,
      and the expression of these genes, showed a significant decrease in the SMA and
      SCOS versus the OA testes (P < 0.005, Kruskal-Wallis test). These findings show
      the low expression of JMJD1A/JMJD1A, as well as its low incorporation into
      chromatin in testes with round spermatid maturation arrest, suggesting that a
      deficient expression of JMJD1A/JMJD1A might be reflecting and/or contributing to
      round spermatid maturation arrest.

PMID- 27692602
TI  - Spermatozoa from infertile patients exhibit differences of DNA methylation
      associated with spermatogenesis-related processes: an array-based analysis.
AB  - The influence of aberrant sperm DNA methylation on the reproductive capacity of
      couples has been postulated as a cause of infertility. This study compared the
      DNA methylation of spermatozoa of 19 fertile donors and 42 infertile patients
      using the Illumina 450K array. Clustering analysis of methylation data arranged
      fertile and infertile patients into two groups. Bivariate clustering analysis
      identified a differential distribution of samples according to the
      characteristics of seminogram and age, suggesting a possible link between these
      parameters and specific methylation profiles. The study identified 696
      differentially methylated cytosine-guanine dinucleotides (CpG) associated with
      501 genes between fertile donors and infertile patients. Ontological enrichment
      analysis revealed 13 processes related to spermatogenesis. Data filtering
      identified a set of 17 differentially methylated genes, some of which had
      functions relating to spermatogenesis. A significant association was identified
      between RPS6KA2 hypermethylation and advanced age (P = 0.016); APCS
      hypermethylation and oligozoospermia (P = 0.041); JAM3/NCAPD3 hypermethylation
      and numerical chromosome sperm anomalies (P = 0.048); and ANK2 hypermethylation
      and lower pregnancy rate (P = 0.040). This description of a set of differentially
      methylated genes provides a framework for further investigation into the
      influence of such variation in male fertility in larger patient cohorts.

PMID- 27692603
TI  - Spanish Catheter Ablation Registry. 15th Official Report of the Spanish Society
      of Cardiology Working Group on Electrophysiology and Arrhythmias (2015).
AB  - INTRODUCTION AND OBJECTIVES: This report presents the findings of the 2015
      Spanish Catheter Ablation Registry. METHODS: For data collection, each center was
      allowed to choose freely between 2 systems: retrospective, requiring the
      completion of a standardized questionnaire, and prospective, involving reporting
      to a central database. RESULTS: Data were collected from 82 centers. A total of
      12 863 ablation procedures were performed, for a mean of 157+/-119 and a median
      of 138 procedures per center. The ablation target most frequently treated was
      cavotricuspid isthmus (n=2992 [23.2%]), followed by atrioventricular nodal
      reentrant tachycardia (n=2966 [23%]) and atrial fibrillation (n=2640 [20.5%]).
      There were fewer ablation procedures for atrial tachycardia, idiopathic
      ventricular tachycardia and accessory pathways, while those for ventricular
      tachycardia in ischemic cardiomyopathy remained steady. The overall success rate,
      excluding atrial fibrillation and ventricular tachycardia in cardiomyopathy, was
      87.5%, the rate of major complications was 2%, and the mortality rate was 0.08%.
      CONCLUSIONS: The 2015 registry is the first to show a slight reduction in the
      number of centers sending in their results and in the total number of ablation
      procedures performed. The most frequently treated substrate was the cavotricuspid
      isthmus. There was also a slight decrease in the success rate. The complications
      and mortality rates remained low.

PMID- 27692604
TI  - Blood management post earthquake 25th April 2015.

PMID- 27692605
TI  - Anti-Xa bioassays for the laboratory measurement of direct Factor Xa inhibitors
      in plasma, in selected patients.
AB  - In the past decade Direct Oral Anti-Coagulants (DOACs), targeting Thrombin or
      Factor Xa, have enormously facilitated the daily treatment of all relevant
      patients, including those requiring lifelong therapy. These DOACs have
      considerable advantages over the use of oral Vitamin K Antagonist (VKA)
      treatments, in view of having little interferences with food and other
      medications and also not requiring adjustment for age, gender or weight, with
      some well-defined exceptions. In this current What's Happening Section we focus
      on measurements of DiXaIs in plasma using anti-Xa assays, with the objective of
      providing a tribute to Professor Michel Meyer Samama, who was not only a real
      leader in this field but, in the past, both authors benefited from his wisdom, as
      a teacher who dedicated his scientific and professional life (among many other
      interests in hemostasis, thrombosis and fibrinolysis) to develop and promote
      methods and strategies for laboratory monitoring of anticoagulants. This review
      presents the performance characteristics of the Anti-Factor Xa assays (measuring
      Factor Xa inhibition by drugs), which are available for measuring Direct Factor
      Xa Inhibitors in plasma, and show good compliance of the results with the
      reference LC:MS method (which measures the mass of Direct Factor Xa Inhibitors).
      We also present the preparation and validation of drug specific plasma
      calibrators and controls which are requested for drug measurements. These assays
      are convenient and practical laboratory tools which can be used in any laboratory
      setting, and meet the requirements of regulatory bodies for making smart,
      quantitative, sensitive, accurate and ease of use assays for measuring DOACs when
      needed. The manuscript focuses mainly on the following areas of current interest:
      interference in coagulation assays; anti-Xa laboratory methods; development of
      calibrators and controls for DiXaIs; method validation and comparison with
      reference techniques (LC:MS); regulatory requirements and method registrations;
      newer clinical applications and experience on DiXaIs with Anti-Xa assays, and
      future perspectives.

PMID- 27692606
TI  - Blood supply during Japan's 1995 Hanshin-Awaji Earthquake.
AB  - On January 17, 1995, a magnitude 7.3 earthquake occurred in southern Hyogo
      Prefecture, a substantially urban area of Japan's main island, Honshu. Now known
      as the Hanshin-Awaji Earthquake, this disaster damaged or destroyed 639 686
      houses and took 6434 lives. Within the disaster area, the Japanese Red Cross
      (JRC) Hyogo Blood Center had regional responsibilities for collecting, testing,
      processing, storing, and distributing blood components, including red blood cells
      (RBCs), fresh frozen plasma (FFP) and platelet concentrates (PLTs). Platelet
      shakers collapsed, forcing the discard of 103 PLT bags (1125 units) that could
      not be temperature-controlled or agitated. RBCs and FFP in refrigerated and
      frozen storage, respectively, remained in temperature control with the help of
      dry ice imported from non-affected areas. Local blood collection was suspended
      and replaced by products from other blood centers. Local demand for blood
      components decreased to 66% of comparable pre-quake demand. Emergent supplies
      rather than reserved supplies of blood components were markedly increased after
      the earthquake. Communication infrastructure damage prompted JRC Hyogo Blood
      Center to send blood delivery vehicles loaded with RBCs and FFP on a circuit of
      main hospitals in the affected area. Local blood donation and processing resumed
      20 days after the quake. In retrospect, a nationally coordinated system of
      production and distribution demonstrated JRC's ability to meet transfusion demand
      after the 1995 Hanshin-Awaji Earthquake, and prompted changes in anticipation of
      subsequent disasters.

PMID- 27692607
TI  - What we have learnt from past disasters, how do we prepare for future calamities?

PMID- 27692608
TI  - Endothelial-to-mesenchymal transition: Cytokine-mediated pathways that determine
      endothelial fibrosis under inflammatory conditions.
AB  - During the last decade, the endothelial-to-mesenchymal transition (EndMT) process
      has attracted considerable attention due to associations with the onset of
      certain diseases, such as organ fibrosis and cancer. Several studies have
      assessed the mechanisms and signaling pathways that regulate endothelial fibrosis
      in the context of human pathologies. A number of inflammatory mediators,
      including pro-inflammatory cytokines, growth factors, oxidative stress, and
      toxins, induce the conversion of endothelial cells into mesenchymal fibroblast
      like cells that promote disease progression. This review is separated into five
      chapters that critically present current knowledge on EndMT in the context of
      pathology. First, the main characteristics of EndMT are summarized, with a focus
      on the endothelial protein pattern changes that modulate the expressions of
      endothelial/fibrotic markers and extracellular matrix proteins. These expressions
      could serve as mechanisms for explaining potential EndMT contributions to human
      pathologies in adults. Second, the main findings supporting a connection between
      EndMT-mediated endothelial fibrosis and inflammatory conditions are presented.
      These connections could be linked to the onset and progression of pathological
      conditions. Third, EndMT inducers are described in detail. This includes
      considerations on the actions of the first and most well-known EndMT inducer, TGF
      beta; of the most prominent pro-inflammatory cytokines released during
      inflammation, such as IL 1-beta and TNF-alpha; and of the NF-kappaB transcription
      factor, a common player during inflammation-induced EndMT. Furthermore, thorough
      attention is given to EndMT induction by endotoxins in the context of bacterial
      infectious diseases. Additionally, the participation of the inflammatory
      oxidative stress environment in the EndMT induction was also reviewed. Fourth,
      the pathophysiological findings of inflammation-induced EndMT are presented, and,
      fifth, special focus is placed on associations with cancer onset and development.
      Altogether, this review highlights the important role of EndMT-mediated
      endothelial fibrosis during inflammation in human pathologies.

PMID- 27692609
TI  - Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria
      Liver-Stage Infection.
AB  - In recent years, various intervention strategies have reduced malaria morbidity
      and mortality, but further improvements probably depend upon development of a
      broadly protective vaccine. To better understand immune requirement for
      protection, we examined liver-stage immunity after vaccination with irradiated
      sporozoites, an effective though logistically difficult vaccine. We identified a
      population of memory CD8+ T cells that expressed the gene signature of tissue
      resident memory T (Trm) cells and remained permanently within the liver, where
      they patrolled the sinusoids. Exploring the requirements for liver Trm cell
      induction, we showed that by combining dendritic cell-targeted priming with liver
      inflammation and antigen recognition on hepatocytes, high frequencies of Trm
      cells could be induced and these cells were essential for protection against
      malaria sporozoite challenge. Our study highlights the immune potential of liver
      Trm cells and provides approaches for their selective transfer, expansion, or
      depletion, which may be harnessed to control liver infections or autoimmunity.

PMID- 27692610
TI  - Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of
      NLRP3 Inflammasome.
AB  - Reciprocal interactions between the metabolic system and immune cells play
      pivotal roles in diverse inflammatory diseases, but the underlying mechanisms
      remain elusive. The activation of bile acid-mediated signaling has been linked to
      improvement in metabolic syndromes and enhanced control of inflammation. Here, we
      demonstrated that bile acids inhibited NLRP3 inflammasome activation via the TGR5
      cAMP-PKA axis. TGR5 bile acid receptor-induced PKA kinase activation led to the
      ubiquitination of NLRP3, which was associated with the PKA-induced
      phosphorylation of NLRP3 on a single residue, Ser 291. Furthermore, this PKA
      induced phosphorylation of NLRP3 served as a critical brake on NLRP3 inflammasome
      activation. In addition, in vivo results indicated that bile acids and TGR5
      activation blocked NLRP3 inflammasome-dependent inflammation, including
      lipopolysaccharide-induced systemic inflammation, alum-induced peritoneal
      inflammation, and type-2 diabetes-related inflammation. Altogether, our study
      unveils the PKA-induced phosphorylation and ubiquitination of NLRP3 and suggests
      TGR5 as a potential target for the treatment of NLRP3 inflammasome-related
      diseases.

PMID- 27692612
TI  - K+ Efflux-Independent NLRP3 Inflammasome Activation by Small Molecules Targeting
      Mitochondria.
AB  - Imiquimod is a small-molecule ligand of Toll-like receptor-7 (TLR7) that is
      licensed for the treatment of viral infections and cancers of the skin. Imiquimod
      has TLR7-independent activities that are mechanistically unexplained, including
      NLRP3 inflammasome activation in myeloid cells and apoptosis induction in cancer
      cells. We investigated the mechanism of inflammasome activation by imiquimod and
      the related molecule CL097 and determined that K+ efflux was dispensable for
      NLRP3 activation by these compounds. Imiquimod and CL097 inhibited the quinone
      oxidoreductases NQO2 and mitochondrial Complex I. This induced a burst of
      reactive oxygen species (ROS) and thiol oxidation, and led to NLRP3 activation
      via NEK7, a recently identified component of this inflammasome. Metabolic
      consequences of Complex I inhibition and endolysosomal effects of imiquimod might
      also contribute to NLRP3 activation. Our results reveal a K+ efflux-independent
      mechanism for NLRP3 activation and identify targets of imiquimod that might be
      clinically relevant.

PMID- 27692611
TI  - Optimal Generation of Tissue-Resident but Not Circulating Memory T Cells during
      Viral Infection Requires Crosspriming by DNGR-1+ Dendritic Cells.
AB  - Despite the crucial role of tissue-resident memory T (Trm) cells in protective
      immunity, their priming remains poorly understood. Here, we have shown
      differential priming requirements for Trm versus circulating memory CD8+ T cells.
      In vaccinia cutaneous-infected mice, DNGR-1-mediated crosspresentation was
      required for optimal Trm cell priming but not for their skin differentiation or
      for circulating memory T cell generation. DNGR-1+ dendritic cells (DCs) promoted
      T-bet transcription-factor induction and retention of CD8+ T cells in the lymph
      nodes (LNs). Inhibition of LN egress enhanced Trm cell generation, whereas
      genetic or antibody blockade of DNGR-1 or specific signals provided during
      priming by DNGR-1+ DCs, such as interleukin-12 (IL-12), IL-15, or CD24, impaired
      Trm cell priming. DNGR-1 also regulated Trm cell generation during influenza
      infection. Moreover, protective immunity depended on optimal Trm cell induction
      by DNGR-1+ DCs. Our results reveal specific priming requirements for CD8+ Trm
      cells during viral infection and vaccination.

PMID- 27692614
TI  - The predictive value of DESH for shunt responsiveness in idiopathic normal
      pressure hydrocephalus.
AB  - OBJECTIVE: Selecting probable idiopathic normal pressure hydrocephalus (INPH)
      patients for shunt insertion presents a challenge because of coexisting
      comorbidities and other conditions that could mimic NPH. The characteristic
      appearance of DESH (Disproportionately Enlarged Subarachnoid Space Hydrocephalus)
      on brain imaging has been shown to have a high positive predictive value in
      identifying shunt responsive INPH patients (SINPHONI trial). However, the
      negative predictive value of this radiological sign was not clearly demonstrated.
      The aim of the present study was to calculate the negative predictive value of
      the DESH sign. METHODS: A single centre study of probable INPH patients, who
      underwent ventriculoperitoneal (VP) shunt insertion. Shunt responsive INPH
      patients were identified as those having improvement in their walking speed,
      neuropsychological assessment and continence one year post operatively.
      Preoperative images were reviewed for DESH sign. Negative and Positive Predictive
      Values (NPV and PPV) of DESH sign were determined post analysis. RESULTS: A total
      of 103 probable INPH patients were included (31 were DESH positive (30%) and 72
      were DESH negative (70%)). A total of 78 patients showed measurable improvement
      one year post shunt insertion (76%); 24 (31%) of these patients were DESH
      positive and 54 (69%) were DESH negative (p=<0.001). Therefore, the DESH sign had
      an estimated PPV of 77% and NPV of 25%. CONCLUSION: DESH sign demonstrates a low
      negative predictive value. We conclude that DESH negative patients should still
      undergo prognostic tests for iNPH, such as an extended lumbar drainage protocol,
      and should not be excluded from shunt insertion.

PMID- 27692615
TI  - Tardily accelerated neurologic deterioration in two-step thallium intoxication.
AB  - Thallium intoxication was reported in cases with accidental ingestion, suicide
      attempt, and criminal adulteration. Reported cases were mostly one-time
      ingestion, therefore, the clinical course of divisional ingestion has not been
      fully known. Here, we report a case with two-step thallium intoxication
      manifesting as tardily accelerated neurologic deterioration. A 16-year-old
      adolescent was cryptically poisoned with thallium sulfate twice at an interval of
      52days. After the first ingestion, neurologic symptoms including visual loss,
      myalgia, and weakness in legs developed about 40days after the development of
      acute gastrointestinal symptoms and alopecia. After the second ingestion,
      neurologic symptoms deteriorated rapidly and severely without gastrointestinal or
      cutaneous symptoms. Brain magnetic resonance imaging exhibited bilateral optic
      nerve atrophy. Nerve conduction studies revealed severe peripheral neuropathies
      in legs. Thallium intoxication was confirmed by an increase in urine thallium
      egestion. Most of the neurologic manifestations ameliorated in two years, but the
      visual loss persisted. The source of thallium ingestion was unraveled afterward
      because a murder suspect in another homicidal assault confessed the forepast
      adulteration. This discriminating clinical course may be attributable to the
      cumulative neurotoxicity due to the longer washout-time of thallium in the
      nervous system than other organs. It is noteworthy that the divisional thallium
      intoxication may manifest as progressive optic and peripheral neuropathy without
      gastrointestinal or cutaneous symptoms.

PMID- 27692617
TI  - Impact of associative word learning on phonotactic processing in 6-month-old
      infants: A combined EEG and fNIRS study.
AB  - During early language development native phonotactics are acquired in a 'bottom
      up' fashion, relying on exquisite auditory differentiation skills operational
      from birth. Since basic lexico-semantic abilities have been demonstrated from 6
      months onwards, 'top-down' influences on phonotactic learning may complement the
      extraction of transitional probabilities in phonotactic learning. Such a
      bidirectional acquisition strategy predicts, that familiarization with
      (proto)words should affect processing of untrained word-forms of similar
      phonological structure. We investigated 6-month-old infants undergoing an
      associative training to establish a pseudoword-pseudoobject link. Comparison
      between pre- and post-training responses to trained and untrained items allowed
      investigating training effects. Additionally phonotactic status (50% legal, 50%
      illegal with regard to German) allowed investigating influences of previous
      language experience. EEG and functional near-infrared spectroscopy (fNIRS)
      provided measures of electrophysiological and hemodynamic responses. We find
      evidence for a robust effect of associative training on pseudoword processing
      when presented in isolation. This transferred to untrained items. Previous
      linguistic experience showed a much weaker effect. Taken together the results
      suggest that sensitivity to phonotactic contrasts is present at 6 months, but
      that acceptance as lexical candidates is rapidly modulated when word forms
      following non-native phonotactics become potentially meaningful due to repeated
      exposure in a semantic context.

PMID- 27692616
TI  - The Intracellular Cholesterol Landscape: Dynamic Integrator of the Immune
      Response.
AB  - Cholesterol has typically been considered an exogenous, disease-related factor in
      immunity; however, recent literature suggests that a paradigm shift is in order.
      Sterols are now recognized to ligate several immune receptors. Altered flux
      through the mevalonic acid synthesis pathway also appears to be a required event
      in the antiviral interferon (IFN) response of macrophages and in the activation,
      proliferation, and differentiation of T cells. In this review, evidence is
      discussed that suggests an intrinsic, 'professional' role for sterols and
      oxysterols in macrophage and T-cell immunity. Host defense may have been the
      original selection pressure behind the development of mechanisms for
      intracellular cholesterol homeostasis. Functional coupling between sterol
      metabolism and immunity has fundamental implications for health and disease.

PMID- 27692618
TI  - Atmospheric Spray Freeze-Drying: Numerical Modeling and Comparison With
      Experimental Measurements.
AB  - Atmospheric spray freeze-drying (ASFD) represents a novel approach to dry
      thermosensitive solutions via sublimation. Tests conducted with a second
      generation ASFD equipment, developed for pharmaceutical applications, have
      focused initially on producing a light, fine, high-grade powder consistently and
      reliably. To better understand the heat and mass transfer physics and drying
      dynamics taking place within the ASFD chamber, 3 analytical models describing the
      key processes are developed and validated. First, by coupling the dynamics and
      heat transfer of single droplets sprayed into the chamber, the velocity,
      temperature, and phase change evolutions of these droplets are estimated for
      actual operational conditions. This model reveals that, under typical operational
      conditions, the sprayed droplets require less than 100 ms to freeze. Second,
      because understanding the heat transfer throughout the entire freeze-drying
      process is so important, a theoretical model is proposed to predict the time
      evolution of the chamber gas temperature. Finally, a drying model, calibrated
      with hygrometer measurements, is used to estimate the total time required to
      achieve a predefined final moisture content. Results from these models are
      compared with experimental data.

PMID- 27692619
TI  - On the Design of a Fuzzy Logic-Based Control System for Freeze-Drying Processes.
AB  - This article is focused on the design of a fuzzy logic-based control system to
      optimize a drug freeze-drying process. The goal of the system is to keep product
      temperature as close as possible to the threshold value of the formulation being
      processed, without trespassing it, in such a way that product quality is not
      jeopardized and the sublimation flux is maximized. The method involves the
      measurement of product temperature and a set of rules that have been obtained
      through process simulation with the goal to obtain a unique set of rules for
      products with very different characteristics. Input variables are the difference
      between the temperature of the product and the threshold value, the difference
      between the temperature of the heating fluid and that of the product, and the
      rate of change of product temperature. The output variables are the variation of
      the temperature of the heating fluid and the pressure in the drying chamber. The
      effect of the starting value of the input variables and of the control interval
      has been investigated, thus resulting in the optimal configuration of the control
      system. Experimental investigation carried out in a pilot-scale freeze-dryer has
      been carried out to validate the proposed system.

PMID- 27692620
TI  - Solubility Advantage (and Disadvantage) of Pharmaceutical Amorphous Solid
      Dispersions.
AB  - The solubility of a drug is ultimately governed by its chemical potential as it
      is present in the undissolved solute. For a pharmaceutical amorphous solid
      dispersion (ASD), its solubility depends on the state and composition of the
      undissolved solute when the ASD is equilibrated with water. Concerning the
      undissolved solute phase that can contain up to 3 components (drug, polymer, and
      water), we developed a complete thermodynamic model to calculate the chemical
      potential of a drug in the multicomponent, amorphous system. This approach
      enables the estimation of the true solubility advantage of ASD from calorimetric
      measurements and moisture sorption isotherms. Both theoretical estimation and
      experimental studies, using indomethacin (IMC)/Eudragit E ASD systems, show that
      the solubility advantage of the amorphous IMC is significantly reduced through
      ASD formation and water partitioning. For the ASD with 70% drug loading, the
      solubility of IMC is lower than its crystalline counterpart. Our results show
      that stabilization through the ASD formation and water sorption can be manifested
      by the lowering of drug solubility; they demonstrate that the core property in
      ASD development is the drug chemical potential, which is essentially the
      thermodynamic driving force and can be quantitated using the model presented in
      this work.

PMID- 27692621
TI  - Use of King Vision(r) videolaryngoscope in an unanticipated difficult airway in
      an adult patient with giant vallecular cyst, a case report.
AB  - Laryngeal cysts are largely asymptomatic and typically described in the context
      of incidental discovery on routine laryngoscopy. These cysts, in adults are even
      rarer and can have catastrophic consequences in an anaesthetized patient if
      airway management is inappropriate. We describe a case of difficult endotracheal
      intubation and the treatment of an adult patient with an asymptomatic, giant
      vallecular cyst that was discovered during rapid-sequence induction of general
      anesthesia in urgent surgery. In conclusion, vallecular cysts can cause extreme
      problems in securing the airway. It is important to avoid complications
      associated with repeated attempts at intubation, airway loss, or cyst rupture
      causing difficulty visualizing vocal cords and aspiration. The use of King
      Vision(r) videolaryngoscope is a good alternative in these cases. Close attention
      to logistics and the immediate availability of an otolaryngologist is vital.

PMID- 27692622
TI  - Establishing the association between nonnutritive sucking behavior and
      malocclusions: A systematic review and meta-analysis.
AB  - BACKGROUND: The authors studied the effects of nonnutritive sucking behavior
      (NNSB) on malocclusions through a systematic review of association (etiology).
      TYPES OF STUDIES REVIEWED: The authors performed a 3-step search strategy,
      including electronic searches. Studies of healthy participants with a history of
      active or previous NNSB, for whom specific malocclusion outcomes had been
      assessed, were eligible for inclusion. The authors considered before-and-after
      studies, prospective and retrospective (longitudinal) studies, case-control
      studies, and analytical cross-sectional studies. They excluded reviews, text- and
      opinion-based articles, conference abstracts, case reports, case-series, and
      descriptive cross-sectional studies. The authors, using standardized instruments,
      independently assessed methodological quality and extracted data from the
      included studies. In situations for which there were sufficient studies, the
      authors conducted meta-analyses using the random-effects model, supplemented with
      the fixed-effects model in situations for which statistical heterogeneity was
      less than 50%, which the authors assessed using the I2 statistic. RESULTS: The
      authors included 15 identified studies. They found that NNSB was associated with
      varying risks of developing malocclusions. Pacifier suckers are less likely to
      develop an increased overjet compared with digit suckers, although the results of
      a meta-analysis of 7 studies whose investigators had assessed posterior crossbite
      in the primary dentition demonstrated a significant association with pacifier
      sucking over digit sucking (n = 5,560; risk ratio, 1.42; 95% confidence interval,
      1.18-1.70; P = .0001). Longer duration of NNSB was associated with an increased
      risk of developing malocclusions. Across-study heterogeneity likely resulted from
      methodological and sample size differences. CONCLUSIONS: The authors of this
      study have confirmed the association between NNSB and the development of
      malocclusions. This study provides the highest level of evidence on this topic.
      Pacifiers were associated with a higher risk of developing most malocclusion
      features when compared with digit sucking. PRACTICAL IMPLICATIONS: Though
      malocclusions are of multifactorial etiology, clinicians should inform parents
      and caregivers about the dental risks of NNSB, an environmental factor that is
      modifiable. NNSB should be discouraged in order to avoid the development of
      malocclusions. Future studies should adopt standardized, universally agreed and
      accepted definitions and classifications when measuring and reporting orthodontic
      outcome measures. This will help achieve across-study homogeneity.

PMID- 27692623
TI  - [Estimation of arterial oxygen saturation in relation to altitude].
AB  - BACKGROUND AND OBJECTIVES: Arterial Oxygen Saturation (AOS) predicts altitude
      sickness. OBJECTIVES: To estimate the AOS values with relation to altitude.
      Furthermore, make a graph to use during activity which assesses the AOS for each
      altitude and the normal range. PATIENTS AND METHOD: Values of AOS were assessed
      during eight high mountain activities in the Alps, Himalaya, Caucasus and Andes;
      53 mountaineers participated, 17 of them in more than one activity; 761
      measurements of AOS were registered. RESULTS: A Logistic Regression Model was
      made to estimate the AOS values dependent on altitude, adjusted to possible
      related factors. A strong lineal relationship exists between altitude and AOS
      (R2=.83, P<.001); .7 points more in women. The AOS in a particular altitude is
      not related to age, weight, height, smoking, heart rate, or even with previous
      experiences in mountains. The calculation of the AOS responds to the follow
      equation: Blood Oxygen Saturation=103.3-(altitude * .0047)+(Z), being Z=.7 in men
      and 1.4 in women. A scatter plot was made to relate the estimated altitude with
      the AOS, with their normal limits values: percentiles 2.5 and 97.5. CONCLUSIONS:
      The simple calculation of the AOS estimated for a particular altitude with the
      proposed graphic can help in the early decision-making onsite.

PMID- 27692624
TI  - [Proximal calciphylaxis: A rare metabolic entity].

PMID- 27692625
TI  - [Left-sided native valve infective endocarditis: Influence of age and the
      presence of underlying heart disease].
AB  - INTRODUCTION AND OBJECTIVES: Left-sided native valve infective endocarditis
      (LNVIE) epidemiology has been modified as a result of the increase in average
      age. The aim of our study is to analyze the influence of age and the presence of
      predisposing heart disease in the prognosis of these patients. METHODS: We
      analyzed a series of 257 cases of LNVIE depending on their age (greater than or
      equal to 70 years old), both in the overall series and in the subgroup of
      patients without predisposing heart disease. RESULTS: Mean age was 54.6 (18.6)
      years. There was an increase in the percentage of cases of older patients between
      1987-2000 and 2001-2014 (9.8 vs. 34.8%, P<.001). These patients present higher
      prevalence of degenerative valves (50 vs. 22.8%) or not predisposing heart
      disease (50 vs. 39.9%), P<.001, health-care associated episodes (41.8 vs. 23.6%,
      P=.016), lower rate of surgery (43.7 vs. 63.8%, P=.005) and higher in-hospital
      mortality (39.1 vs. 20.7%, P=.003), with no differences in comorbidities. Older
      patients who did not have predisposing heart disease also suffered higher in
      hospital mortality (47 vs. 22%, P=.01). Age greater than or equal to 70 years old
      is an independent predictor of mortality in patients with LNVIE (OR 2.53, 95% CI
      1.24-5.15, P=.011), as in those without previous heart disease (OR 3.98, 95% CI
      1.49-10.62, P=.006). CONCLUSIONS: Patients of age greater than or equal to 70
      years old and who suffer an LNVIE are becoming more frequent and have a worse
      prognosis with a lower rate of surgery and higher rates of in-hospital mortality.

PMID- 27692626
TI  - The utility of a "trauma 1 OP" activation at a level 1 pediatric trauma center.
AB  - PURPOSE: To expedite flow of injured children suspected to require operative
      intervention, a "trauma 1 OP" (T1OP) activation classification was created. The
      purpose of this study was to review this strategy at a level 1 pediatric trauma
      center. METHODS: A retrospective review of T1OP activations between 2003 and 2015
      was performed. Children suspected of requiring neurosurgical intervention were
      classified as trauma 1 OP neuro (T1OP(N)). Comparisons were made to trauma 1 (T1)
      patients who required emergent operative intervention, excluding orthopedic
      injuries. RESULTS: Overall, 461 T1OP activations occurred (72% T1OP(N)) compared
      to 129 T1 activations requiring emergent surgery. Demographics were not
      significantly different between groups, although T1OP patients were slightly
      younger and more often experienced falls or were victims of abuse. Compared to T1
      activations, T1OP activations had a significantly higher mortality rate (21% vs.
      7%, p<0.001). Repeat head imaging was more common in the T1OP(N) group compared
      to imaged children in the T1 group (20% vs. 37%, p=0.05). T1OP(N) patients more
      often went directly to the OR (45% vs. 33%, p=0.02) and did so in a significantly
      faster period of time (32min vs. 53min, p<0.001). CONCLUSIONS: Use of the T1OP
      activations appropriately triaged surgical patients, resulting in significantly
      faster transport times to the OR. LEVEL OF EVIDENCE: II, prognosis study.

PMID- 27692627
TI  - Does a large abdominal wall defect affect lung growth?
AB  - BACKGROUND/PURPOSE: Respiratory distress in babies with large abdominal wall
      defects suggests a relationship to decreased diaphragmatic movement. We evaluated
      pulmonary development in a fetal lamb gastroschisis model. METHODS: We created
      gastroschisis in 25 fetal lambs at 60days gestation (group A). Controls were 14
      nonoperated lambs. (Group B) were all delivered at term. Lung volume, histology,
      and type 1 (AT1)/type 2 (AT2) cell ratios (AT1 ratio) were determined. We
      subdivided group A, comparing lambs with a large defect and scoliosis [group A
      (S)] with the remainder [group A (NS)]. RESULTS: Twenty-five lambs survived (11
      fetuses in group A and 14 fetuses in group B). Lung volume in group A (S) was
      less than in group A (NS) (p<0.05). The AT1 ratio in group A was lower than in
      group B (p<0.01), without any difference in radial alveolar counts (RACs) or
      alveolar growth, and no association between scoliosis and alveolar
      differentiation. CONCLUSION: Gastroschisis in a sheep model reduces the AT1 ratio
      but not the RAC. Severe scoliosis affects lung volume but not the AT1 ratio,
      suggesting reduced diaphragmatic movement in fetuses with large abdominal
      defects.

PMID- 27692628
TI  - Preferred Healthy Food Nudges, Food Store Environments, and Customer Dietary
      Practices in 2 Low-Income Southern Communities.
AB  - OBJECTIVE: To examine how food store environments can promote healthful eating,
      including (1) preferences for a variety of behavioral economics strategies to
      promote healthful food purchases, and (2) the cross-sectional association between
      the primary food store where participants reported shopping, dietary behaviors,
      and body mass index. METHODS: Intercept survey participants (n = 342) from 2
      midsized eastern North Carolina communities completed questionnaires regarding
      preferred behavioral economics strategies, the primary food store at which they
      shopped, and consumption of fruits, vegetables, and sugary beverages. RESULTS:
      Frequently selected behavioral economic strategies included: (1) a token and
      reward system for fruit and vegetable purchases; and (2) price discounts on
      healthful foods and beverages. There was a significant association between the
      primary food store and consumption of fruits and vegetables (P = .005) and sugary
      beverages (P = .02). CONCLUSIONS AND IMPLICATIONS: Future studies should examine
      associations between elements of the in-store food environment, purchases, and
      consumption.

PMID- 27692629
TI  - Engaging Caregivers in School-Based Obesity Prevention Initiatives in a
      Predominantly Latino Immigrant Community: A Qualitative Analysis.
AB  - OBJECTIVES: To explore caregiver perceptions of, and barriers and facilitators
      to, their involvement in school-based obesity prevention programs in underserved
      Latino immigrant communities. METHODS: Focus groups discussions were conducted
      with caregivers (n = 42) at 7 elementary schools with an academic partnership
      based obesity prevention program. Thematic analysis was used to identify key
      findings in the data. RESULTS: Caregivers described their role as (1) learners of
      new and often complex health information using their children as primary
      messengers and (2) champions within their homes in which healthier choices are
      assimilated. Barriers to involvement included lack of time, financial pressures,
      unhealthy family practices, and concern that attempts to engage peers would be
      perceived as intrusive. Facilitators included assurance that stigmatizing health
      issues would be addressed with sensitivity. CONCLUSIONS AND IMPLICATIONS:
      Caregiver involvement in obesity prevention may be fostered by transmitting
      information through children, addressing cultural barriers, and avoiding
      potentially stigmatizing approaches to delivering health messages.

PMID- 27692630
TI  - Employees' Expectations of Internet-Based, Workplace Interventions Promoting the
      Mediterranean Diet: A Qualitative Study.
AB  - OBJECTIVE: Explore employees' perceptions of ability to follow the Mediterranean
      diet (MedDiet), preferences for setting goals if asked to follow the MedDiet, and
      expectations of an Internet-based, workplace MedDiet intervention. DESIGN: Seven
      focus groups to guide intervention development. SETTING: Four workplaces
      (business/professional services, government branches) in Southwest England.
      PARTICIPANTS: Employees (n = 29, 51.7% women), ages 24-58 years. PHENOMENON OF
      INTEREST: Ability to follow the MedDiet; preferences for goal-setting if asked to
      follow the MedDiet; intervention content. ANALYSIS: Data were analyzed with the
      use of thematic analysis. RESULTS: Participants perceived that adhering to some
      MedDiet recommendations would be challenging and highlighted cost, taste, and
      cooking skills as adherence barriers. Behavior change preferences included a
      tailored approach to goal-setting, reviewing goal progress via a
      website/smartphone app, and receiving expert feedback via an
      app/website/text/face-to-face session. Desirable features of an Internet-based
      MedDiet application included recipes, interactivity, nutritional information,
      shopping tips, cost-saving information, and a companion smartphone app. Engaging
      in social support was deemed important to facilitate adherence. CONCLUSIONS AND
      IMPLICATIONS: An Internet-based, workplace MedDiet intervention should address
      adherence barriers, utilize a tailored approach to setting and reviewing goals,
      and activate social support to facilitate adherence. These findings provide
      insights to planning to promote the MedDiet in non-Mediterranean regions.

PMID- 27692631
TI  - [Map of resources and healthcare needs for patients with dyslipidaemia in Spain:
      The MADI study].
AB  - INTRODUCTION: Dyslipidaemia is a major modifiable determining factor of vascular
      risk and, despite this, a significant number of patients do not achieve lipid
      goals. The aim of this study is to describe the resources and current needs in
      clinical practice in Spain, through an analysis of management, organisation and
      the patient care circuit of dyslipidaemia patient. METHODS: A descriptive, cross
      sectional, multicentre study, using a questionnaire, was conducted on physicians,
      266 in primary care (PC) and 258 in specialised care (SC), who attended patients
      with dyslipidaemia in hospitals and centres within the National Health System.
      Probabilistic analyses were performed, stratifying by care-level, existence of a
      lipid unit (LU), and geographic area. RESULTS: Observed differences were mostly
      due to geographic location, rather than the existence of LU in the referral
      hospitals. Most system deficiencies were found in the southern provinces of the
      country. Nearly all primary care physicians declared that they diagnose, manage
      and control dyslipidaemia patients, but a general agreement was lacking for
      diagnostic and referral criteria. The scarce use of a shared protocol between PC
      and SC showed evidence of poor coordination between health care providers.
      Furthermore, there was a remarkably low proportion of patients receiving health
      care education for their disease. CONCLUSIONS: This study emphasises the need to
      identify weaknesses in the dyslipidaemia patient care circuit, and to perform the
      appropriate remedial actions, in particular, to promote coordination between
      levels of care and to foster patient education about their disease.

PMID- 27692632
TI  - Nonalcoholic fatty liver disease, association with cardiovascular disease and
      treatment (II). The treatment of nonalcoholic fatty liver disease.
AB  - Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of
      histologically similar to those induced by alcohol consumption in people with
      very little or no liver damage same. The importance of NAFLD is its high
      prevalence in our Western societies, from the point of view liver in its
      progressive evolution from steatosis to steatohepatitis, cirrhosis and liver
      cancer. During the last decade it has been observed that NAFLD leads to an
      increased cardiovascular risk with accelerated atherosclerosis and cardiovascular
      events, the leading cause of morbidity and mortality. This updated January 2016
      revision consists of two parts. In this second part, the treatment of NAFLD and
      its influence on cardiovascular disease and drugs used in the control of
      cardiovascular risk factors showing a beneficial effect on the liver disease will
      be reviewed.

PMID- 27692633
TI  - Nonalcoholic fatty liver disease, association with cardiovascular disease and
      treatment. (I). Nonalcoholic fatty liver disease and its association with
      cardiovascular disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically
      lesions similar to those induced by alcohol consumption in people with very
      little or no liver damage. The importance of NAFLD is its high prevalence in the
      Western world and, from the point of view of the liver, in its gradual
      progression from steatosis to steatohepatitis, cirrhosis, and liver cancer.
      During the last decade it has been observed that NAFLD leads to an increased
      cardiovascular risk with acceleration of arteriosclerosis and events related to
      it, being the main cause of its morbidity and mortality. This review, updated to
      January 2016, consists of two parts, with the first part analysing the
      association of NAFLD with cardiovascular disease.

PMID- 27692634
TI  - [Inflammation inhibits vascular fibulin-5 expression: Involvement of
      transcription factor SOX9].
AB  - INTRODUCTION: Fibulin-5 (FBLN5) is an elastogenic protein critically involved in
      extracellular matrix (ECM) remodelling, a key process in abdominal aortic
      aneurysm (AAA). However, the possible contribution of FBLN5 to AAA development
      has not been addressed. METHODS: Expression levels were determined by real-time
      PCR and Western blot in human abdominal aorta from patients with AAA or healthy
      donors, as well as in human aortic vascular smooth muscle cells (VSMC).
      Lentiviral transduction, transient transfections, and chromatin
      immunoprecipitation (ChIP) assays were also performed. RESULTS: The expression of
      FBLN5 in human AAA was significantly lower than in healthy donors. FBLN5 mRNA and
      protein levels and their secretion to the extracellular environment were down
      regulated in VSMC exposed to inflammatory stimuli. Interestingly, FBLN5
      transcriptional activity was inhibited by TNFalpha and lipopolysaccharide (LPS),
      and depends on a SOX response element. In fact, SOX9 expression was reduced in
      VMSC induced by inflammatory mediators and in human AAA, and correlated with that
      of FBLN5. Furthermore, SOX9 over-expression limited the reduction of FBLN5
      expression induced by cytokines in VSMC. Finally, it was observed that SOX9
      interacts with FBLN5 promoter, and that this binding was reduced upon TNFalpha
      exposure. CONCLUSIONS: FBLN5 downregulation in human AAA could contribute to
      extracellular matrix remodelling induced by the inflammatory component of the
      disease.

PMID- 27692635
TI  - [Is regression of atherosclerotic plaque possible?]
AB  - As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic
      plaque causes most acute coronary syndromes. Plaque stabilization via reduction
      of the lipid core and/or thickening of the fibrous cap is one of the possible
      mechanisms accounted for the clinical benefits displayed by different anti
      atherosclerotic strategies. The concept of plaque stabilization was developed to
      explain how lipid-lowering agents could decrease adverse coronary events without
      substantial modifications of the atherosclerotic lesion ('angiographic paradox').
      A number of imaging modalities (vascular ultrasound and virtual histology, MRI,
      optical coherence tomography, positron tomography, etc.) are used for non
      invasive assessment of atherosclerosis; most of them can identify plaque volume
      and composition beyond lumen stenosis. An 'aggressive' lipid-lowering strategy is
      able to reduce the plaque burden and the incidence of cardiovascular events; this
      may be attributable, at least in part, to plaque-stabilizing effects.

PMID- 27692636
TI  - Burn injuries from exploding electronic cigarette batteries: An emerging public
      health hazard.

PMID- 27692637
TI  - A Review of Ferric Pyrophosphate Citrate (Triferic) Use in Hemodialysis Patients.
AB  - PURPOSE: The objective of this short review is to evaluate the efficacy of ferric
      pyrophosphate citrate and to determine its place in therapy based on the current
      published literature. METHODS: A literature search was conducted and pared down
      to yield 4 placebo controlled Phase II and III clinically relevant trials.
      FINDINGS: Ferric pyrophosphate citrate is a new intradialytic iron
      supplementation product that has been found to reduce the dose of erythropoiesis
      stimulating agents and intravenous iron supplementation and to increase serum
      ferritin concentrations. IMPLICATIONS: This agent may be administered to patients
      with stage 5 chronic kidney disease receiving hemodialysis as a new iron
      supplementation option to maintain hemoglobin, transferrin saturation, and
      ferritin concentrations.

PMID- 27692638
TI  - Single- and Multiple-dose Pharmacokinetics of a Lorcaserin Extended-release
      Tablet.
AB  - PURPOSE: Lorcaserin is a serotonin 2C receptor agonist indicated for chronic
      weight management as an adjunct to diet and exercise. The initial approved
      formulation is a 10-mg, immediate-release (IR) tablet for administration BID.
      These studies investigated the single- and multiple-dose pharmacokinetic
      properties of a new, recently US Food and Drug Administration-approved, extended
      release, 20-mg once-daily formulation. METHODS: We performed 2 separate 2-period,
      2-sequence crossover studies in 36 healthy adults: a study comparing the IR
      formulation to the extended-release formulation under fasting conditions and a
      study comparing the extended-release formulation under fed and fasted conditions.
      FINDINGS: Compared with lorcaserin IR, the Tmax after a single dose of lorcaserin
      extended-release was greater (median, 12 vs 3 hours), and the Cmax was 26% lower
      (38.8 vs 52.3 ng/mL). AUC data were bioequivalent for the 2 formulations in both
      single- and multiple-dose regimens, confirming no formulation effect on
      lorcaserin bioavailability. In fasted and fed conditions, Tmax after a single
      dose was identical (median, 12 hours), but Cmax was approximately 45% higher in
      the fed state (mean, 38.5 ng/mL fasted vs 56.1 ng/mL fed). However, at steady
      state, Cmax and AUC were determined to be bioequivalent between the fasted and
      fed states, indicating no clinically relevant food effect on the pharmacokinetic
      properties of lorcaserin extended-release. The safety profile was consistent
      between the 2 formulations. IMPLICATIONS: Overall, the results indicate that
      lorcaserin extended-release is a suitable once-daily alternative to the approved
      IR BID formulation.

PMID- 27692639
TI  - 7,10-Diphenylfluoranthene grafted polysiloxane as a highly selective stationary
      phase for gas chromatography.
AB  - A novel 7,10-diphenylfluoranthene grafted polysiloxane (DPFP) was synthesized and
      statically coated on a fused-silica capillary column. High column efficiency
      (3864 plates per m) was achieved for naphthalene at 120 degrees C. Thermo
      gravimetric analysis showed that the DPFP polymer began to decompose at 380
      degrees C. The chromatogram of polyethylene pyrolysis products indicated that the
      maximum allowable temperature of the DPFP column could reach 360 degrees C. By
      relying on its specific pi-pi stacking and dipole-induced dipole interactions
      with aromatic solutes, the DPFP stationary phase achieved excellent resolution
      for substituted benzene and aromatic hydrocarbons with satisfactory peak shapes,
      as well as showed superiority to current stationary phases that failed to resolve
      some critical pairs. Moreover, DPFP also showed good selectivity and resolving
      ability for Grob test mixtures, fatty acid esters, and ethers.

PMID- 27692640
TI  - Sequence-dependent separation of trinucleotides by ion-interaction reversed-phase
      liquid chromatography-A structure-retention study assisted by soft-modelling and
      molecular dynamics.
AB  - We studied sequence-dependent retention properties of synthetic 5'-terminal
      phosphate absent trinucleotides containing adenine, guanine and thymine through
      reversed-phase liquid chromatography (RPLC) and QSRR modelling. We investigated
      the influence of separation conditions, namely mobile phase composition (ion
      interaction agent content, pH and organic constituent content), on sequence
      dependent separation by means of ion-interaction RPLC (II-RPLC) using two types
      of models: experimental design-artificial neural networks (ED-ANN), and linear
      regression based on molecular dynamics data. The aim was to determine those
      properties of the above-mentioned analytes responsible for the retention
      dependence of the sequence. Our results show that there is a deterministic
      relation between sequence and II-RPLC retention properties of the studied
      trinucleotides. Further, we can conclude that the higher the content of ion
      interaction agent in the mobile phase, the more prominent these properties are.
      We also show that if we approximate the polar component of solvation energy in
      QSRR by the electrostatic work in transferring molecules from vacuum to water,
      and the non-polar component by the solvent accessible surface area, these
      parameters best describe the retention properties of trinucleotides. There are
      some exceptions to this finding, namely sequences 5'-NAN-3', 5'-ANN-3', 5'-TGN
      3', 5'-NTA-3'and 5'-NGA-3' (N stands for generic nucleotide). Their role is still
      unknown, but since linear regression including these specific constellations
      showed a higher observable variance coverage than the model with only the basic
      descriptors, we may assume that solvent-analyte interactions are responsible for
      the exceptional behaviour of 5'-NAN-3' & 5'-ANN-3' trinucleotides and some
      intramolecular interactions of neighbouring nucleobases for 5'-TGN-3', 5'-NTA
      3'and 5'-NGA-3' trinucleotides.

PMID- 27692641
TI  - Preparation and evaluation of micro and meso porous silica monoliths with
      embedded carbon nanoparticles for the extraction of non-polar compounds from
      waters.
AB  - A novel hybrid micro and meso porous silica monolith with embedded carbon
      nanoparticles (Si-CNPs monolith) was prepared inside a fused silica capillary
      (3cm in length) and used as a sorbent for solid-phase microextraction. The hybrid
      monolithic capillary was synthetized by hydrolysis and polycondensation of a
      mixture of tetraethoxysilane (TEOS), ethanol, and three different carbon
      nanoparticles such as carboxylated single-walled carbon nanotubes (c-SWCNTs),
      carboxylated multi-walled carbon nanotubes (c-MWCNTs), and oxidized single-walled
      carbon nanohorns (o-SWNHs) via a two-step catalytic sol-gel process. Compared
      with silica monolith without carbon nanoparticles, the developed monolithic
      capillary column exhibited a higher extraction efficiency towards the analytes
      which can be ascribed to the presence of the carbon nanoparticles. In this
      regard, the best performance was achieved for silica monolith with embedded c
      MWCNTs. The resulted monolithic capillaries were also characterized by scanning
      electron microscopy (SEM), elemental analysis and nitrogen intrusion porosimetry.
      Variables affecting to the preparation of the sorbent phase including three
      different carbon nanoparticles and extraction parameters were studied in depth
      using polycyclic aromatic hydrocarbons (PAHs) as target analytes. Gas
      chromatography-mass spectrometry was selected as instrumental technique.
      Detection limits range from 0.1 to 0.3MUgL-1, and the inter-extraction units
      precision (expressed as relative standard deviation) is between 5.9 and 14.4%.

PMID- 27692642
TI  - Implant stability after sinus floor augmentation with deproteinized bovine bone
      mineral particles of different sizes: a prospective, randomized and controlled
      split-mouth clinical trial.
AB  - The aim of this study was to compare implant stability after maxillary sinus
      floor augmentation using small- or large-sized particles of Bio-Oss. Ten
      partially edentulous patients requiring bilateral maxillary sinus floor
      augmentation were enrolled. The subjects were assigned randomly to one of two
      experimental groups: maxillary sinus was filled with 0.25-1mm particle size
      (small particles) and the contralateral side was filled with 1-2mm particle size
      (large particles). After 8 months, a total of 25 implants were placed in the two
      maxillary sinuses. Primary implant stability was measured immediately after
      implant placement (T0) using a torque controller and resonance frequency analysis
      (RFA). Six months after implant placement (T1), the implant stability was
      measured again. There were no postoperative complications in either particle size
      group, and the success rate for implant survival was 100%. All implants showed
      good primary stability as evidenced by high torque for the implant insertion in
      both groups. RFA revealed high ISQ values for all implants installed in both
      groups at T0 and T1. These results indicate that the size of the Bio-Oss
      particles (small and large) did not influence implant stability in the maxillary
      sinus. Indeed, small and large particles of Bio-Oss presented optimal properties,
      supporting their possible use as osteoconductive grafts.

PMID- 27692644
TI  - Acute dyspnea by diaphragmatic excursion: practicality sustainable in ED?

PMID- 27692645
TI  - Separation properties of the MIL-125(Ti) Metal-Organic Framework in high
      performance liquid chromatography revealing cis/trans selectivity.
AB  - Monodisperse MIL-125(Ti) Metal-Organic Framework crystals were synthesized and
      studied as stationary phase in high performance liquid chromatography (HPLC).
      Different pure compounds and model mixtures (including stereoisomer mixtures)
      were injected from which chromatographic parameters, including selectivities and
      resolution factors, were determined to evaluate the adsorption properties and
      separation performance of MIL-125(Ti) in liquid phase. The MIL-125(Ti) framework
      displayed a trans selectivity for cis/trans difunctionalized cyclohexane
      molecules with high selectivity and resolution for 1,3-dimethylcyclohexane and 4
      ethylcyclohexanol. The slurry-packed column was further characterized via van
      Deemter analysis. Fitting of the van Deemter equation through the experimental
      points allowed to define the contributions of the different processes to plate
      height with a significant proportion of the A-term, reflecting the importance of
      a good crystal packing. Although high in comparison to commercial HPLC stationary
      phases, a very good plate height of around 50MUm was found.

PMID- 27692643
TI  - Elimination of visceral leishmaniasis on the Indian subcontinent.
AB  - Visceral leishmaniasis is a serious public health problem on the Indian
      subcontinent, causing high morbidity and mortality. The governments in the region
      launched a visceral leishmaniasis elimination initiative in 2005. We review
      knowledge gaps and research priorities. Key challenges include low coverage of
      health services for those most at risk, drug resistance, the absence of a
      vaccine, and the complex biology of the sandfly-human host transmission cycle.
      Vector control is an essential component, but innovation in this field is
      insufficient. Substantial progress has been made in the area of diagnostic,
      therapeutic, and vaccine development, but there are still many hurdles to
      overcome. For visceral leishmaniasis elimination to become a reality, effective
      deployment of these existing and new tools is essential. A strong commitment at
      community level is imperative, and appropriate diagnostic and treatment services
      as well as effective epidemiological surveillance need to be ensured.

PMID- 27692646
TI  - Microfluidic nitrogen-assisted nanoelectrospray emitter: A monolithic interface
      for accurate mass measurements based on a single nozzle.
AB  - Nitrogen-assisted nanoelectrospray emitter (NANE) was developed to achieve
      accurate mass-to-charge ratio (m/z) measurements with a single monolithic nozzle.
      Deposition patterns of generated electrosprays from NANE confirmed their wrapped
      configurations. Additionally, the intensity of the sample ion and its ratio
      relative to a reference ion was inclined to focus on the central region of the
      spray; this trend further supported the existence of wrapped configurations.
      Further, the proposed NANE was fabricated from poly-(dimethylsiloxane) (PDMS)
      with octadecyltrichlorosilane modification to restrain the dissolution of PDMS
      monomers. Assist nitrogen flows were introduced to improve the ionization of
      reference ions. Moreover, the NANE could regulate the distribution of reference
      ions by microfluidic three dimensional hydrodynamic focusing. By regulating the
      distribution of reference ions, the ionization depression was reduced to some
      degree, and an improved sensitivity was accomplished compared with the mixing of
      sample and reference solutions. Achieved relative errors of m/z were between 0.2
      4.5ppm and 5.2-9.2ppm for ten organic molecules and four biological
      macromolecules, respectively. Acceptable linear ranges were obtained in
      quantifications for rhodamine B and emamectin benzoate. Finally, the NANE was
      compatible with broad infusion rates (from 50nLmin-1 to 15MULmin-1) and solutions
      of different compositions (from 100% methanol to 100% water). Considering the
      comprehensive application of PDMS in microfluidics, the proposed NANE could be
      used as a compact and monolithic interface to achieve accurate m/z measurements.

PMID- 27692647
TI  - The effect of charged groups on hydrophilic monolithic stationary phases on their
      chromatographic properties.
AB  - In order to investigate the effect of charged groups present in hydrophilic
      monolithic stationary phases on their chromatographic properties, three charged
      hydrophilic monomers, i.e. N,N-dimethyl-N-acryloyloxyethyl-N-(3
      sulfopropyl)ammonium betaine (SPDA), [2-(acryloyloxy)ethyl]trimethylammonium
      chloride (AETA), and 3-sulfopropyl acrylate potassium salt (SPA) were co
      polymerized with the crosslinker N,N'-methylenebisacrylamide (MBA), respectively.
      The physicochemical properties of the three resulting charged hydrophilic
      monolithic columns were evaluated using scanning electron microscopy, zeta
      potential analysis and micro-HPLC. High column efficiency was obtained on the
      three monolithic columns at a linear velocity of 1mm/s using thiourea as test
      compound. Comparative characterization of the three charged HILIC phases was then
      carried out using a set of model compounds, including nucleobases, nucleosides,
      benzoic acid derivatives, phenols, beta-blockers and small peptides. Depending on
      the combination of stationary phase/mobile phase/solute, both hydrophilic
      interaction and other potential secondary interactions, including electrostatic
      interaction, hydrogen-bonding interaction, molecular shape selectivity, could
      contribute to the over-all retention of the analytes. Because of the strong
      electrostatic interaction provided by the quaternary ammonium groups in the poly
      (AETA-co-MBA) monolith, this cationic HILIC monolith exhibited the strongest
      retention for benzoic acid derivatives and small peptides with distorted peak
      shapes and the weakest retention for basic beta-blockers. The sulfonyl groups on
      the poly (SPA-co-MBA) hydrophilic monolith could provide strong electrostatic
      attraction and hydrogen bonding for positively charged analytes and hydrogen
      donor/acceptor containing analytes, respectively. Therefore, basic drugs,
      nucleobases and nucleotides exhibited the strongest retention on this anionic
      monolith. Because of the weak but distinct cation exchange properties of the
      zwitterionic poly (SPDA-co-MBA) hydrophilic monolith, it exhibited the best
      separation for most test analytes (including phenols, beta-blockers and small
      peptides) in terms of selectivity, peak shape and analysis time. The poly (AETA
      co-MBA) hydrophilic monolithic column provides the best separation of nucleobases
      and nucleosides. These results could guide the selection and application of these
      charged HILIC monoliths in the future.

PMID- 27692648
TI  - Development of stable isotope dilution assays for the quantitation of intra- and
      extracellular folate patterns of Bifidobacterium adolescentis.
AB  - Folate-producing bifidobacteria have been studied extensively but appropriate
      methods for detailed quantitation of intra- and extracellular pteroylmono- and
      pteroylpolyglutamate patterns are lacking. Therefore, B. adolescentis DSM 20083T
      was cultivated in folate-free medium (FFM) for 24h to develop and validate stable
      isotope dilution assays (SIDAs) coupled with LC-MS/MS for the determination of 5
      formyltetrahydrofolic acid (5-HCO-H4folate), 10-formylfolic acid (10-HCO-PteGlu),
      tetrahydrofolic acid (H4folate), folic acid (PteGlu) and 5-methyltetrahydrofolic
      acid (5-CH3-H4folate) including its di-, tri-, and tetraglutamic vitamers (5-CH3
      H4PteGlu2-4). The respective monoglutamylated isotopologues labelled with
      deuterium were used as internal standards for quantitation. Limits of detection
      and quantitation (LOD/LOQ) were sufficiently low to quantify 48.2nmol L-1 5-CH3
      H4folate (5.7/17nmolL-1) and 71.0nmolL-1 5-HCO-H4folate (10/30nmolL-1) as major
      folate vitamers extracellularly and 124nmolL-1 5-CH3-H4folate (3.4/10nmolL-1),
      213nmolL-1 5-HCO-H4folate (4.8/14nmolL-1), and 61.4nmolL-1 H4folate (2.3/7.0nmolL
      1) intracellularly after deconjugation. The major portion of native 5-CH3
      H4folate vitamer was ascribed to its tetraglutamate ( > 95%). Concentrations of
      mono-, di-, tri-, and pentaglutamylated folates were below LOD or LOQ. Intra
      assay precision coefficients of variation (CVs) ranged from 7% (at a
      concentration of 53.9nmolL-1 for 5-CH3-H4PteGlu4), 15% (25.5nmolL-1 5-CH3
      H4folate) to 18% (78.5nmolL-1 5-HCO-H4folate), extracellularly, and from 6%
      (60.7nmolL-1 5-CH3-H4PteGlu4), 7% (202nmolL-1 5-HCO-H4folate), 10% (67.1nmolL-1
      H4folate) to 11% (127nmolL-1 5-CH3-H4folate), intracellularly. Inter-assay
      precision CVs ranged from 2% (54.7nmolL-1 5-CH3-H4PteGlu4), 3% (71nmolL-1 5-HCO
      H4folate) to 11% (48.2nmolL-1 5-CH3-H4folate), extracellularly, and from 1%
      (61.4nmolL-1 H4folate), 5% (213nmolL-1 5-HCO-H4folate), 6% (63.5nmolL-1 5-CH3
      H4PteGlu4) to 10% (124nmolL-1 5-CH3-H4folate), intracellularly, thus showing
      excellent reproducibility. Recoveries for all analytes under study ranged between
      81 and 113%. These newly developed methods enable reproducible, precise and
      sensitive quantitation of eight bacterially synthesized folate vitamers in two
      totally different matrices, including both monoglutamates and polyglutamates.
      Furthermore, we here present the first assay using solely monoglutamylated [2H4]
      5-CH3-H4folate to quantify native polyglutamate patterns of this vitamer in
      bacteria which might replace time-consuming determination of monoglutamates in
      the future.

PMID- 27692649
TI  - Does the National Resident Match Program Rank List Predict Success in Emergency
      Medicine Residency Programs?
AB  - BACKGROUND: Emergency medicine (EM) residency programs use nonstandardized
      criteria to create applicant rank lists. One implicit assumption is that
      predictive associations exist between an applicant's rank and their future
      performance as a resident. To date, these associations have not been sufficiently
      demonstrated. OBJECTIVES: We hypothesized that a strong positive correlation
      exists between the National Resident Match Program (NRMP) match-list applicant
      rank, the United States Medical Licensing Examination (USMLE) Step 1 and In
      Training Examination (ITE) scores, and the graduating resident rank. METHODS: A
      total of 286 residents from five EM programs over a 5-year period were studied.
      The applicant rank (AR) was derived from the applicant's relative rank list
      position on each programs' submitted NRMP rank list. The graduation rank (GR) was
      determined by a faculty consensus committee. GR was then correlated to AR using a
      Spearman's partial rank correlation. Additional correlations were sought with a
      ranking of the USMLE Step Score (UR) and the ITE Score (IR). RESULTS: Combining
      data for all five programs, weak positive correlations existed between GR and AR,
      UR, and IR. The majority of correlations ranged between. When comparing GR and
      AR, there was a weak correlation of 0.13 (p = 0.03). CONCLUSION: Our study found
      only weak correlations between GR and AR, UR, and IR, suggesting that those
      variables may not be strong predictors of resident performance. This has
      important implications for EM programs considering the resources devoted to
      applicant evaluation and ranking.

PMID- 27692650
TI  - Predictors of Nondiagnostic Ultrasound for Appendicitis.
AB  - BACKGROUND: Ionizing radiation and cost make ultrasound (US), when available, the
      first imaging study for the diagnosis of suspected pediatric appendicitis. US is
      less sensitive and specific than computed tomography (CT) or magnetic resonance
      imaging (MRI) scans, which are often performed after nondiagnostic US.
      OBJECTIVES: We sought to determine predictors of nondiagnostic US in order to
      guide efficient ordering of imaging studies. METHODS: A prospective cohort study
      of consecutive patients 4 to 30 years of age with suspected appendicitis took
      place at an emergency department with access to 24/7 US, MRI, and CT
      capabilities. Patients with US as their initial study were identified. Clinical
      (i.e., duration of illness, highest fever, and right lower quadrant pain) and
      demographic (i.e., age and sex) variables were collected. Body mass index (BMI)
      was calculated based on Centers for Disease Control and Prevention criteria; BMI
      >85th percentile was categorized as overweight. Patients were followed until day
      7. Univariate and stepwise multivariate logistic regression analysis was
      performed. RESULTS: Over 3 months, 106 patients had US first for suspected
      appendicitis; 52 (49%) had nondiagnostic US results. Eighteen patients had
      appendicitis, and there were no missed cases after discharge. On univariate
      analysis, male sex, a yearly increase in age, and overweight BMI were associated
      with nondiagnostic US (p < 0.05). In the multivariate model, only BMI (odds ratio
      4.9 [95% CI 2.0-12.2]) and age (odds ratio 1.1 [95% CI 1.02-1.20]) were
      predictors. Sixty-eight percent of nondiagnostic US results occurred in
      overweight patients. CONCLUSION: Overweight and older patients are more likely to
      have a nondiagnostic US or appendicitis, and it may be more efficient to consider
      alternatives to US first for these patients. Also, this information about the
      accuracy of US to diagnose suspected appendicitis may be useful to clinicians who
      wish to engage in shared decision-making with the parents or guardians of
      children regarding imaging options for children with acute abdominal pain.

PMID- 27692651
TI  - Best Clinical Practice: Current Controversies in the Evaluation of Low-Risk Chest
      Pain with Risk Stratification Aids. Part 2.
AB  - BACKGROUND: Chest pain accounts for 10% of emergency department (ED) visits
      annually, and many of these patients are admitted because of potentially life
      threatening conditions. A substantial percentage of patients with chest pain are
      at low risk for a major cardiac adverse event (MACE). OBJECTIVE: We investigated
      controversies in the evaluation of patients with low-risk chest pain, including
      clinical scores, decision pathways, and shared decision-making. DISCUSSION: ED
      patients with chest pain who have negative biomarker results and nonischemic
      electrocardiograms are at low risk for MACE. With the large number of chest pain
      patients evaluated in the ED, several risk scores and pathways are in use based
      on history, electrocardiographic results, and biomarker results. The Thrombolysis
      in Myocardial Infarction and Global Registry of Acute Coronary Events scores are
      older rules with validation; however, they do not have adequate sensitivity or
      are not easy to use in the ED. The Vancouver chest pain and North American chest
      pain rules may be used for patients with undifferentiated chest pain in the ED.
      The Manchester Acute Coronary Syndromes rule uses eight factors, several of which
      are not available in the United States. The history, electrocardiography, age,
      risk factors, and troponin (HEART) score and pathway are easy to use, have high
      sensitivity and negative predictive values, and have better discriminatory
      capability for categorization. The use of pathways with shared decision-making
      involves the patient in management, shortens the duration of stay, and decreases
      risk to both the patient and the provider. CONCLUSIONS: Risk stratification of ED
      patients with chest pain has evolved, and there are many tools available. The
      HEART pathway, designed for ED use, has several attributes that provide safe and
      efficient care for patients with chest pain.

PMID- 27692652
TI  - Risk factors for developing prediabetes.

PMID- 27692653
TI  - [Analysis of an intervention to improve health outcomes in acute exacerbations of
      COPD in primary care].
AB  - OBJECTIVE: To examine the impact of an intervention by Primary Care (PC)
      professionals of a Health District on the clinical outcomes for treating COPD
      exacerbations using a process and outcome indicators analysis (clinical audit).
      DESIGN: Observational, retrospective and prospective analysis cross-sectional
      audit of clinical practice SETTING: Malaga-Guadalhorce Sanitary District (DSMG).
      PARTICIPANTS: Patients with COPD exacerbations treated by the extra-hospital
      emergency services (n=523; 21% losses). INTERVENTIONS: Professional training in
      the usual clinical practice and inclusion of process indicators of COPD targets
      in relation to incentives. PRINCIPAL MEASUREMENTS: Comparison of external audit
      results (process and outcomes variables) from medical records and Health Outcomes
      (exacerbations, admissions). Variable response: Difference in exacerbations and
      admissions in 2 periods analysed. Bivariate and multivariate analysis. RESULTS:
      Mean age was 75 (+/-9.3), 63.7% males with a BMI of 29.4 (+/-7.1), and 21% active
      smokers. Mean FEV1, 48.2% (+/-18.7). Mean exacerbations in the first period, 2.86
      (+/-2.29) and in the second 1.36 (+/-1.56) (P<.001). Mean hospital admissions in
      the first and second period, 0.56 (+/-0.94) and 0.31 (+/-0.66) (P<.001),
      respectively. The decrease in the number of exacerbations was directly associated
      with having >=2 exacerbations in the first period, reviewed in Primary Care, and
      inversely with heart failure and with having >=2 exacerbations in the second
      period (R2=0.28; P<.001) CONCLUSIONS: The number of exacerbations and admissions
      decreased significantly in both periods assessed. However, the evaluated process
      indicators did not improve. Prospective intervention studies are necessary to
      establish the possible causal relationship.

PMID- 27692655
TI  - Catatonia Delirium: 3 Cases Treated With Memantine.

PMID- 27692654
TI  - The Prevalence and Specificity of Depression Diagnosis in a Clinic-Based
      Population of Adults With Type 2 Diabetes Mellitus.
AB  - OBJECTIVE: To estimate the crude prevalence of minor depressive disorder (MinD)
      in a clinic-based population of adults with type 2 diabetes. METHODS: We screened
      a clinical sample of 702 adults with type 2 diabetes for depressive symptoms
      using the Patient Health Questionnaire-2 and performed a structured diagnostic
      psychiatric interview on 52 screen-positive and a convenience sample of 51 screen
      negative individuals. Depressive disorder diagnoses were made using Diagnostic
      and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria and
      categorized as MinD, major depressive disorder (MDD), or no depressive disorder.
      We estimated prevalence of MinD and MDD and derived 95% CIs. RESULTS: The crude
      prevalence of current, past, and current or past MinD was 4.3% (95% CI: 0.9
      9.2%), 9.6% (95% CI: 3.9-15.9%), and 13.9% (95% CI: 7.7-21.2%), respectively. The
      crude prevalence of current, past, and current or past MDD was slightly higher
      5.0% (95% CI: 1.9-9.4%), 12.0% (95% CI: 6.1-19.5%), and 17.0% (95% CI: 10.1
      24.8%), respectively. There was a high prevalence of coexisting anxiety disorders
      in individuals with MinD (42.2%) and MDD (8.1%). Hemoglobin A1c levels were not
      significantly different in individuals with MinD or MDD compared to those without
      a depressive disorder. CONCLUSIONS: MinD is comparably prevalent to MDD in
      patients with type 2 diabetes; both disorders are associated with concomitant
      anxiety disorders. MinD is not included in the DSM-5; however, our data support
      continuing to examine patients with chronic medical conditions for MinD.

PMID- 27692656
TI  - Preparticipation Cardiac Screening in Young Athletes: In Search of the Golden
      Chalice.

PMID- 27692657
TI  - Detecting Underlying Cardiovascular Disease in Young Competitive Athletes.
AB  - BACKGROUND: Sudden cardiac death (SCD) is frequently the first manifestation of
      underlying cardiovascular disease in young competitive athletes (YCAs), yet there
      are no Canadian guidelines for preparticipation screening in this population. The
      goal of this study was to determine the prevalence of potentially lethal
      cardiovascular disease in a sample of Canadian YCAs by comparing 2 screening
      strategies. METHODS: We prospectively screened 1419 YCAs in British Columbia,
      Canada (age 12-35 years). We initially screened 714 YCAs using the American Heart
      Association 12-element recommendations, physical examination, and
      electrocardiogram (ECG) examination (phase 1). This strategy yielded a high
      number of false positive results; 705 YCAs were subsequently screened using a
      novel SportsCardiologyBC (SCBC) questionnaire and ECG examination in the absence
      of a physical examination (phase 2). RESULTS: Overall, 7 YCAs (0.52%) were found
      to have clinically significant diagnoses associated with SCD (4 pre-excitation, 1
      long QT syndrome, 1 mitral valve prolapse, 1 hypertrophic cardiomyopathy). Six of
      the 7 athletes (85.7%) with disease possessed an abnormal ECG. Conversely, only 2
      had a positive personal or family history (1 athlete had an abnormal ECG and
      family history). The SCBC questionnaire and protocol (phase 2) was associated
      with fewer false positive screens; 3.7% (25 of 679) compared with 8.1% (55 of
      680) in phase 1 (P = 0.0012). CONCLUSIONS: The prevalence of conditions
      associated with SCD in a cohort of Canadian YCAs was comparable with American and
      European populations. The SCBC questionnaire and protocol were associated with
      fewer false positive screens. The ECG identified most of the positive cases
      irrespective of screening strategy used.

PMID- 27692659
TI  - Postoperative assessment of left ventricular function by two-dimensional strain
      (speckle tracking) after paediatric cardiac surgery.
AB  - BACKGROUND: Left ventricular (LV) dysfunction may complicate paediatric cardiac
      surgery with cardiopulmonary bypass, notably after long aortic cross-clamping
      (ACC). Assessment of occult myocardial injury by conventional echocardiographic
      variables may be difficult in the postoperative period. AIMS: To evaluate the
      feasibility of two-dimensional (2D) strain in the postoperative period, and to
      assess the effect of ACC duration on this variable. METHODS: Thirty-three
      paediatric patients (age<18years) with congenital heart disease undergoing
      cardiac surgery with cardiopulmonary bypass were included in this prospective
      single-centre study. Daily echocardiography was performed from the day before
      surgery to the fifth postoperative day. LV ejection fraction and LV 2D strain
      were measured. The cohort was divided into three groups according to ACC duration
      (group 1:<30minutes; group 2: 30-80minutes; group 3:>80minutes). RESULTS: Mean
      age and weight were 4.2+/-2.5years and 15.1+/-5.2kg, respectively. Feasibilities
      of longitudinal, circumferential and radial strains were good, and quite similar
      to conventional variables. Compared with conventional variables, intra- and
      interobserver agreements regarding 2D strain were better (r=0.916, P<0.001 and
      r=0.855, P<0.001 for longitudinal strain versus r=0.156, P=0.54 and r=0.064,
      P=0.80 for LV ejection fraction by Simpson's method). Postoperative evolution of
      longitudinal and circumferential strains was significantly different between the
      three groups (P<0.001), whereas there was no difference using conventional
      variables. CONCLUSION: Postoperative LV 2D strain is a feasible and reproducible
      method. Strain measurements seem to indicate correlation with ACC duration.

PMID- 27692658
TI  - Localization of gaps during redo ablations of paroxysmal atrial fibrillation:
      Preferential patterns depending on the choice of cryoballoon ablation or
      radiofrequency ablation for the initial procedure.
AB  - BACKGROUND: Pulmonary vein (PV) isolation, using cryoballoon or radiofrequency
      ablation, is the cornerstone therapy for symptomatic paroxysmal atrial
      fibrillation (AF) refractory to antiarrhythmic drugs. One-third of the patients
      have recurrences, mainly due to PV reconnections. AIMS: To describe the different
      locations of reconnection sites in patients who had previously undergone
      radiofrequency or cryoballoon ablation, and to compare the characteristics of the
      redo procedures in both instances. METHODS: Demographic data and characteristics
      of the initial ablation (cryoballoon or radiofrequency) were collected. Number
      and localization of reconduction gaps, and redo characteristics were reviewed.
      RESULTS: Seventy-four patients scheduled for a redo ablation of paroxysmal AF
      were included; 38 had been treated by radiofrequency ablation and 36 by
      cryoballoon ablation during the first procedure. For the initial ablation,
      procedural and fluoroscopy times were significantly shorter for cryoballoon
      ablation (147.8+/-52.6min vs. 226.6+/-64.3min [P<0.001] and 37.0+/-17.7min vs.
      50.8+/-22.7min [P=0.005], respectively). Overall, an identical number of gaps was
      found during redo procedures of cryoballoon and radiofrequency ablations.
      However, a significantly higher number of gaps were located in the right superior
      PV for patients first ablated with radiofrequency (0.9+/-1.0 vs. 0.5+/-0.9;
      P=0.009). Gap localization displayed different patterns. Although not
      significant, redo procedures of cryoballoon ablation were slightly shorter and
      needed shorter durations of radiofrequency to achieve PV isolation. CONCLUSIONS:
      During redo procedures, gap localization pattern is different for patients first
      ablated with cryoballoon or radiofrequency ablation, and right superior PV
      reconnections occur more frequently after radiofrequency ablation. Redo ablation
      of a previous cryoballoon ablation appears to be easier.

PMID- 27692660
TI  - Therapeutic hypothermia to protect the heart against acute myocardial infarction.
AB  - The cardioprotective effect of therapeutic hypothermia (32-34 degrees C) has been
      well demonstrated in animal models of acute myocardial infarction. Beyond infarct
      size reduction, this protection was associated with prevention of the no-reflow
      phenomenon and long-term improvement in terms of left ventricular remodelling and
      performance. However, all these events were observed when hypothermia was induced
      during the ischaemic episode, and most benefits virtually vanished after
      reperfusion. This is consistent with clinical findings showing a lack of benefit
      from hypothermia in patients presenting acute myocardial infarction in most
      trials. In these studies, hypothermia was most often achieved too far into the
      reperfusion phase (i.e. possibly too late to reduce infarct size); this is
      supported by meta-analyses and subgroup analyses suggesting that the benefits of
      hypothermia could still be observed in patients with a large infarction and more
      rapid cooling before reperfusion. Novel strategies for ultra-fast induction of
      hypothermia and/or prehospital cooling might therefore be more beneficial.

PMID- 27692661
TI  - Usefulness of 3-Tesla cardiac magnetic resonance imaging in the assessment of
      aortic stenosis severity in routine clinical practice.
AB  - BACKGROUND: Recently, 1.5-Tesla cardiac magnetic resonance imaging (CMR) was
      reported to provide a reliable alternative to transthoracic echocardiography
      (TTE) for the quantification of aortic stenosis (AS) severity. Few data are
      available using higher magnetic field strength MRI systems in this context. AIMS:
      To evaluate the feasibility and reproducibility of the assessment of aortic valve
      area (AVA) using 3-Tesla CMR in routine clinical practice, and to assess
      concordance between TTE and CMR for the estimation of AS severity. METHODS:
      Ninety-one consecutive patients (60 men; mean age 74+/-10years) with known AS
      documented by TTE were included prospectively in the study. RESULTS: All patients
      underwent comprehensive TTE and CMR examination, including AVA estimation using
      the TTE continuity equation (0.81+/-0.18cm2), direct CMR planimetry (CMRp)
      (0.90+/-0.22cm2) and CMR using Hakki's formula (CMRhk), a simplified Gorlin
      formula (0.70+/-0.19cm2). Although significant agreement with TTE was found for
      CMRp (r=0.72) and CMRhk (r=0.66), CMRp slightly overestimated (bias=0.11+/
      0.18cm2) and CMRhk slightly underestimated (bias=-0.11+/-0.17cm2) AVA compared
      with TTE. Inter- and intraobserver reproducibilities of CMR measurements were
      excellent (r=0.72 and r=0.74 for CMRp and r=0.88 and r=0.92 for peak aortic
      velocity, respectively). CONCLUSION: 3-Tesla CMR is a feasible, radiation-free,
      reproducible imaging modality for the estimation of severity of AS in routine
      practice, knowing that CMRp tends to overestimate AVA and CMRhk to underestimate
      AVA compared with TTE.

PMID- 27692662
TI  - Place of non-vitamin K antagonist oral anticoagulants in anticoagulant
      antiplatelet combinations in peripheral artery disease.
AB  - Non-vitamin K antagonist oral anticoagulants are becoming increasingly important
      in the prophylaxis and treatment of thrombosis in atrial fibrillation and venous
      thromboembolism. Antiplatelets are widely prescribed in the primary and secondary
      prevention of cardiac and vascular diseases. There are potentially numerous
      situations where anticoagulants and antiplatelets may be combined; these
      combinations have been explored in coronary artery disease, and some have been
      included in updated recommendations. Is it legitimate to transpose these
      recommendations to the management of peripheral artery disease? The specific
      characteristics of the treated vessels, the stents used, the respective
      frequencies of stent thrombosis and its effect on the target organ are probably
      different, and explain why opinions differ. However, because of a lack of
      evidence, empirical behaviours are being established without scientific
      validation. This review of the literature details the situations in which
      combinations of an anticoagulant and an antiplatelet have been explored in
      peripheral artery disease. We discuss the issue of antithrombotic combinations in
      stable peripheral artery disease and for vascular or endovascular surgery.

PMID- 27692663
TI  - Decisions by Default: Incomplete and Contradictory MOLST in Emergency Care.
AB  - OBJECTIVES: What patients intend when they make health care choices and whether
      they understand the meaning of orders for life-sustaining treatment forms is not
      well understood. The purpose of this study was to analyze the directives from a
      sample of emergency department (ED) patients' MOLST forms. PROCEDURES: MOLST
      forms that accompanied 100 patients who were transported to an ED were collected
      and their contents analyzed. Data categories included age, gender, if the patient
      completed the form for themselves, medical orders for life-sustaining treatment
      including intubation, ventilation, artificial nutrition, artificial fluids or
      other treatment, and wishes for future hospitalization or transfer. Frequencies
      of variables were calculated and the associations between them were determined
      using chi-square. An a priori list of combinations of medical orders that were
      contradictory was developed. Contradictions with Orders for CPR (cardiopulmonary
      resuscitation) included the choice of one or more of the following: Comfort care;
      Limited intervention; Do Not Intubate; No rehospitalization; No IV (intravenous)
      fluids; and No antibiotics. Contradictions with DNR orders included the choice of
      one or more of the following: Intubation; No limitation on interventions.
      Contradictions with orders for Comfort Care were as follows: Send to the
      hospital; Trial period of IV fluids; Antibiotics. The frequencies of coexisting
      but contradictory medical orders were calculated using crosstabs. Free text
      responses to the "other instructions" section were submitted to content analysis.
      RESULTS: Sixty-nine percent of forms reviewed had at least one section left
      blank. Inconsistencies were found in patient wishes among a subset (14%) of
      patients, wherein their desire for "comfort measures only" seemed contradicted by
      a desire to be sent to the hospital, receive IV fluids, and/or receive
      antibiotics. CONCLUSIONS: Patients and proxies may believe that making choices
      and documenting some, but not all, of their wishes on the MOLST form is
      sufficient for directing their end-of-life care. The result of making some, but
      not all, choices may result in patients receiving undesired, extraordinary, or
      invasive care.

PMID- 27692664
TI  - Quality standards versus nutritional taxes: Health and welfare impacts with
      strategic firms.
AB  - The goal of this paper is to better understand firms' strategic reactions to
      nutritional policies targeting food quality improvements and to derive optimal
      policies. We propose a model of product differentiation, taking into account the
      taste and health characteristics of products. We study how two firms react to
      alternative policies: an MQS policy, linear taxation of the two goods on the
      market, and taxation of the low-quality good. The MQS and the taxation of the low
      quality product are the preferred options by a social planner. If taste is
      moderately important, the MQS policy is chosen by a populist and a paternalist
      social planner. If taste is a major component of choice, the populist planner
      chooses to tax the low-quality product whereas the paternalist planner prefers
      the MQS policy. Finally, for a paternalist social planner, an MQS-based policy
      always allows for higher levels of welfare than an information policy alone.

PMID- 27692665
TI  - SPCA2 couples Ca2+ influx via Orai1 to Ca2+ uptake into the Golgi/secretory
      pathway.
AB  - Dysregulation of the Golgi/Secretory Pathway Ca2+ transport ATPase SPCA2 is
      implicated in breast cancer. During lactation and in luminal breast cancer types,
      SPCA2 interacts with the plasma membrane Ca2+ channel Orai1, promoting
      constitutive Ca2+ influx, which is termed store independent Ca2+ entry (SICE).
      The mechanism of SPCA2/Orai1 interaction depends on the N- and C-termini of
      SPCA2. These extensions may play a dual role in activating not only Orai1, but
      also Ca2+ transport into the Golgi/secretory pathway, which we tested by
      investigating the impact of various SPCA2 N- and/or C-terminal truncations on
      SICE and Ca2+ transport activity of SPCA2. C-terminal truncations impair SICE and
      SPCA2 activity, but also affect targeting, whereas N-terminal truncations affect
      targeting and inactivate SPCA2, but remarkably, SICE activation remains
      unaffected. Importantly, overexpression of SPCA2 increases the Ca2+ content of
      non-ER stores, which depends on Orai1 and SPCA2 activity. Thus, Orai1-mediated
      Ca2+-influx and SPCA2-mediated Ca2+ uptake activity into the Golgi/secretory
      pathway might be coupled possibly in a microdomain. This channel/pump complex may
      efficiently transfer Ca2+ into the secretory pathway, which might play a role in
      SPCA2-expressing secretory cells, such as mammary gland during lactation.

PMID- 27692666
TI  - Experiences and needs of parents of critically injured children during the acute
      hospital phase: A qualitative investigation.
AB  - INTRODUCTION: Physical injury is a leading cause of death and disability among
      children worldwide and the largest cause of paediatric hospital admission.
      Parents of critically injured children are at increased risk of developing mental
      and emotional distress in the aftermath of child injury. In the Australian
      context, there is limited evidence on parent experiences of child injury and
      hospitalisation, and minimal understanding of their support needs. The aim of
      this investigation was to explore parents' experiences of having a critically
      injured child during the acute hospitalisation phase of injury, and to determine
      their support needs during this time. METHODS: This multi-centre study forms part
      of a larger longitudinal mixed methods study investigating the experiences, unmet
      needs and well-being of parents of critically injured children over the two-year
      period following injury. This paper describes parents' experiences of having a
      child 0-13 years hospitalised with critical injury in one of four Australian
      paediatric hospitals. Semi-structured interviews were conducted with forty
      parents and transcribed verbatim. The data were managed using NVIVO 10 software
      and thematically analysed. FINDINGS: Forty parents (26 mothers and 14 fathers) of
      30 children (14 girls and 16 boys aged 1-13 years) from three Australian States
      participated. The majority of children were Australian born. Three main themes
      with sub-themes were identified: navigating the crisis of child injury; coming to
      terms with the complexity of child injury; and finding ways to meet the family's
      needs. CONCLUSIONS: There is a need for targeted psychological care provision for
      parents of critically injured children in the acute hospital phase, including
      psychological first aid and addressing parental blame attribution. Parents and
      children would benefit from the implementation of anticipatory guidance
      frameworks informed by a family-centred social ecological approach to prepare
      them for the trauma journey and for discharge. This approach could inform care
      delivery throughout the child injury recovery trajectory. The development and
      implementation of a major trauma family support coordinator in paediatric trauma
      centres would make a tangible difference to the care of critically injured
      children and their families.

PMID- 27692667
TI  - Dynamic behavior of hydroxyl radical in sono-photo-Fenton mineralization of
      synthetic municipal wastewater effluent containing antipyrine.
AB  - The aim of this study was to examine the kinetics of the different mechanisms
      (radical pathway, photolysis, molecular reaction with H2O2 and reaction with
      ultrasonically generated oxidative species) involved in the homogeneous sono
      photoFenton (US/UV/H2O2/Fe) mineralization of antipyrine present in a synthetic
      municipal wastewater effluent (ASMWE). The dynamic behavior of hydroxyl (HO)
      radical generation and consumption in mineralization reaction under different
      systems was investigated by measuring hydroxyl radical concentration during the
      reaction. The overall mineralization process was optimized using a Central
      Composite Experimental Design (CCED) with four variables (initial concentrations
      of H2O2 and Fe(II), amplitude and pulse length). The response functions (pseudo
      first order mineralization kinetic rate constants) were fitted using neural
      networks (NNs). Under the optimal conditions ([H2O2]o=500mgL-1, [Fe(II)]o=27mgL
      1, Amplitude (%)=20andPulse length=1), the TOC removal was 79% in 50min. The
      radical reaction in the bulk solution was found be the primary mineralization
      pathway (94.8%), followed by photolysis (3.65%), direct reaction with H2O2
      (0.86%), and reaction by ultrasonically generated oxidative species (0.64%). The
      role of the Fe catalyst on the radical reaction and the presence of refractory
      intermediates towards hydroxyl radical were also studied.

PMID- 27692668
TI  - Intraperitoneal chemotherapy after interval debulking surgery for advanced-stage
      ovarian cancer: Feasibility and outcomes at a comprehensive cancer center.
AB  - OBJECTIVES: Intraperitoneal (IP)-based chemotherapy following primary debulking
      surgery (PDS), although associated with substantial toxicity, is supported by a
      strong evidence base. We sought to determine feasibility and outcomes of IP
      chemotherapy after interval debulking surgery (IDS) among patients deemed
      ineligible for PDS. METHODS: We identified all patients with high-grade, stage
      III/IV ovarian cancer treated at our institution with neoadjuvant chemotherapy
      (NACT) followed by IDS and postoperative chemotherapy from 1/2008-5/2013. IP and
      intravenous (IV) regimens were defined; demographic and clinical data were
      analyzed using appropriate statistics. RESULTS: Of 128 evaluable patients, 118
      (92%) achieved <=1cm residual disease at IDS and 74 (58%) achieved a complete
      gross resection (CGR). An IP port was placed in 54/128 patients (42%), with 89%
      port utilization. Forty-eight (38%) of 128 patients received IP chemotherapy, 17
      (13%) weekly IV paclitaxel/q3week carboplatin, and 63 (49%) q3week IV
      carboplatin/paclitaxel. Patients completed a median of 3 IP cycles (range, 2-6),
      with 3 (5.5%) of 54 ports removed due to complications. Overall survival (OS) for
      patients with a CGR treated with IP and weekly IV chemotherapy was 53.2months
      (range, 24.7-NE), and 44.2months (range, 30.2-NE) with any visible residual
      disease (p<0.001). Median OS was 53.2months (range, 44.5-NE) for IP-, not reached
      for weekly IV-, and 34.2months (range, 27.5-49.8) for q3week IV-treated patients
      (p=0.1). CONCLUSIONS: Patients administered IP after IDS had a high rate of
      successful port utilization, with few regimen switches. Oncologic outcomes were
      optimal in patients with a CGR at IDS, regardless of chemotherapy used.

PMID- 27692670
TI  - Strategies to broaden the cross-protective efficacy of vaccines against porcine
      reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most
      economically important viral pathogens currently affecting swine production
      worldwide. Although PRRS vaccines have been commercially available for over 20
      years, the available vaccines are considered inadequately effective for control
      and eradication of the virus. Major obstacles for the development of a highly
      effective PRRS vaccine include the highly variable nature of the viral genome,
      the viral ability to subvert the host immune system, and the incomplete
      understanding of the immune protection against PRRSV infection. This article
      summarizes the impediments for the development of a highly protective PRRS
      vaccine and reviews the vaccinology approaches that have been attempted to
      overcome one of the most formidable challenges, which is the substantial genetic
      variation among PRRSV isolates, to broaden the antigenic coverage of PRRS
      vaccines.

PMID- 27692669
TI  - Disease extent at secondary cytoreductive surgery is predictive of progression
      free and overall survival in advanced stage ovarian cancer: An NRG
      Oncology/Gynecologic Oncology Group study.
AB  - PURPOSE: GOG 152 was a randomized trial of secondary cytoreductive surgery (SCS)
      in patients with suboptimal residual disease (residual tumor nodule >1cm in
      greatest diameter) following primary cytoreductive surgery for advanced stage
      ovarian cancer. The current analysis was undertaken to evaluate the impact of
      disease findings at SCS on progression-free survival (PFS) and overall survival
      (OS). METHODS: Among the 550 patients enrolled on GOG-152, two-hundred-sixteen
      patients were randomly assigned following 3cycles of cisplatin and paclitaxel to
      receive SCS. In 15 patients (7%) surgery was declined or contraindicated. In the
      remaining 201 patients the operative and pathology reports were utilized to
      classify their disease status at the beginning of SCS as; no gross
      disease/microscopically negative N=40 (19.9%), no gross disease/microscopically
      positive N=8 (4.0%), and gross disease N=153 (76.1%). RESULTS: The median PFS for
      patients with no gross disease/microscopically negative was 16.1months, no gross
      disease/microscopically positive was 13.5months and for gross disease was
      11.7months, P=0.002. The median OS for patients with no gross
      disease/microscopically negative was 51.5months, no gross disease/microscopically
      positive was 42.6months and for gross disease was 34.9months, P=0.018.
      CONCLUSION: Although as previously reported SCS did not change PFS or OS, for
      those who underwent the procedure, their operative and pathologic findings were
      predictive of PFS and OS. Surgical/pathological residual disease is a biomarker
      of response to chemotherapy and predictive of PFS and OS.

PMID- 27692671
TI  - Increasing compliance with the World Health Organization Surgical Safety
      Checklist-A regional health system's experience.
AB  - BACKGROUND: In 2009, NorthShore University HealthSystem adapted the World Health
      Organization Surgical Safety Checklist (SSC) at each of its 4 hospitals. Despite
      evidence that SSC reduces intraoperative mistakes and increase patient safety,
      compliance was found to be low with the paper form. In November 2013, NorthShore
      integrated the SSC into the electronic health record (EHR). The aim was to
      increase communication between operating room (OR) personnel and to encourage
      best practices during the natural workflow of surgeons, anesthesiologists, and
      nurses. The purpose of this study was to examine the impact of an electronic SSC
      on compliance and patient safety. METHODS: An anonymous OR observer selected
      cases at random and evaluated the compliance rate before the rollout of the
      electronic SSC. In June 2014, an electronic audit was performed to assess the
      compliance rate. Random OR observations were also performed throughout the summer
      in 2014. Perioperative risk events, such as consent issues, incorrect counts,
      wrong site, and wrong procedure were compared before and after the electronic SSC
      rollout. A perception survey was also administered to NorthShore OR personnel.
      RESULTS: Compliance increased from 48% (n = 167) to 92% (n = 1,037; P < .001)
      after the SSC was integrated into the electronic health record. Surgeons (91% vs
      97%; P < .001), anesthesiologists (89% vs 100%; P < .001), and nurses (55% vs
      93%; P < .001) demonstrated an increase in compliance. A comparison between risk
      events in the pre- and post-rollout period showed a 32% decrease (P < .01).
      Hospital-wide indicators including length of stay and 30-day readmissions were
      lower. In a survey to assess the OR personnel's perceptions of the new checklist,
      76% of surgeons, 86% of anesthesiologists, and 88% of nurses believed the
      electronic SSC will have a positive impact on patient safety. CONCLUSIONS: The
      World Health Organization SSC is a validated tool to increase patient safety and
      reduce intraoperative complications. The electronic SSC has demonstrated an
      increased compliance rate, a reduced number of risk events, and most OR personnel
      believe it will have a positive impact on patient safety.

PMID- 27692673
TI  - Percutaneous thermal ablation of primary lung cancer.
AB  - Percutaneous ablation of small-size non-small-cell lung cancer (NSCLC) has
      demonstrated feasibility and safety in nonsurgical candidates. Radiofrequency
      ablation (RFA), the most commonly used technique, has an 80-90% reported rate of
      complete ablation, with the best results obtained in tumors less than 2-3cm in
      diameter. The highest one-, three-, and five-year overall survival rates reported
      in NSCLC following RFA are 97.7%, 72.9%, and 55.7% respectively. Tumor size,
      tumor stage, and underlying comorbidities are the main predictors of survival.
      Other ablation techniques such as microwave or cryoablation may help overcome the
      limitations of RFA in the future, particularly for large tumors or those close to
      large vessels. Stereotactic ablative radiotherapy (SABR) has its own
      complications and carries the risk of fiducial placement requiring multiple lung
      punctures. SABR has also demonstrated significant efficacy in treating small-size
      lung tumors and should be compared to percutaneous ablation.

PMID- 27692672
TI  - Road traffic noise, blood pressure and heart rate: Pooled analyses of harmonized
      data from 88,336 participants.
AB  - INTRODUCTION: Exposure to road traffic noise may increase blood pressure and
      heart rate. It is unclear to what extent exposure to air pollution may influence
      this relationship. We investigated associations between noise, blood pressure and
      heart rate, with harmonized data from three European cohorts, while taking into
      account exposure to air pollution. METHODS: Road traffic noise exposure was
      assessed using a European noise model based on the Common Noise Assessment
      Methods in Europe framework (CNOSSOS-EU). Exposure to air pollution was estimated
      using a European-wide land use regression model. Blood pressure and heart rate
      were obtained by trained clinical professionals. Pooled cross-sectional analyses
      of harmonized data were conducted at the individual level and with random-effects
      meta-analyses. RESULTS: We analyzed data from 88,336 participants, across the
      three participating cohorts (mean age 47.0 (+/-13.9) years). Each 10dB(A)
      increase in noise was associated with a 0.93 (95% CI 0.76;1.11) bpm increase in
      heart rate, but with a decrease in blood pressure of 0.01 (95% CI -0.24;0.23)
      mmHg for systolic and 0.38 (95% CI -0.53; -0.24) mmHg for diastolic blood
      pressure. Adjustments for PM10 or NO2 attenuated the associations, but remained
      significant for DBP and HR. Results for BP differed by cohort, with negative
      associations with noise in LifeLines, no significant associations in EPIC-Oxford,
      and positive associations with noise >60dB(A) in HUNT3. CONCLUSIONS: Our study
      suggests that road traffic noise may be related to increased heart rate. No
      consistent evidence for a relation between noise and blood pressure was found.

PMID- 27692674
TI  - Evaluation of tumor response to intra-arterial chemoembolization of
      hepatocellular carcinoma: Comparison of contrast-enhanced ultrasound with
      multiphase computed tomography.
AB  - PURPOSE: To compare the diagnostic accuracy of contrast-enhanced ultrasound
      (CEUS) with that of multiphase computed tomography (CT) in the evaluation of
      tumor response to transarterial chemoembolization (TACE) of hepatocellular
      carcinoma (HCC). MATERIAL AND METHODS: Fifty patients (41 men, 9 women; mean age,
      53 years+/-12.5 [SD]) with a total of 70 HCCs (mean size, 5cm+/-3 [SD]) were
      evaluated. Post-TACE therapeutic assessment of HCC was done at 4 weeks. Patients
      with TACE done earlier and reporting with suspicion for recurrence were also
      included. Patients with hepatic masses seen on ultrasound were enrolled and
      subjected to CEUS, multiphase CT and magnetic resonance imaging (MRI).
      Hyperenhancing area at the tumor site on arterial phase of CEUS/multiphase CT/MRI
      was termed as residual disease (RD), the patterns of which were described on
      CEUS. Diagnostic accuracies of CEUS and MPCT were compared to that of MRI that
      was used as the reference standard. RESULTS: CEUS detected RD in 43/70 HCCs
      (61%). RD had a heterogeneous pattern in 22/43 HCCs (51%). Sensitivities of CEUS
      and multiphase CT were 94% (34/36; 95% CI: 81-99%) and 50% (18/36; 95% CI: 33
      67%) respectively. Significant difference in sensitivity was found between CEUS
      and multiphase CT (P=0.0001). CEUS and multiphase CT had 100% specificity (95%
      CI: 83-100%). CONCLUSION: CEUS is a useful technique for detecting RD in HCC
      after TACE. For long term surveillance, CEUS should be complemented with
      multiphase CT/MRI for a comprehensive evaluation.

PMID- 27692675
TI  - Radiological evaluation of response to neoadjuvant treatment in pancreatic
      cancer.
AB  - Neoadjuvant chemotherapy has become common practice in the management of patients
      with non-metastatic pancreatic adenocarcinoma. This strategy helps better select
      patients who would benefit from surgical resection and also increase the number
      of patients amenable to surgical resection whose tumor seemed too locally
      advanced on initial imaging. However, several studies have shown that the
      radiological evaluation of the response after neoadjuvant therapy is difficult
      for pancreatic carcinoma. This article reviews the scientific basis of
      neoadjuvant therapy for non-metastatic pancreatic cancer and provides an update
      on tumor response evaluation with imaging after neoadjuvant treatment.

PMID- 27692676
TI  - Sudden death and cardiac arrest without phenotype: the utility of genetic
      testing.
AB  - Approximately 4% of sudden cardiac deaths are unexplained [the sudden arrhythmic
      death syndrome (SADS)], and up to 6-10% of survivors of cardiac arrest do not
      have an identifiable cardiac abnormality after comprehensive clinical evaluation
      [idiopathic ventricular fibrillation (IVF)]. Genetic testing may be able to play
      a role in diagnostics and can be targeted to an underlying phenotype present in
      family members following clinical evaluation. Alternatively, post-mortem genetic
      testing (the "molecular autopsy") may diagnose the underlying cause if a clearly
      pathogenic rare variant is found. Limitations include a modest yield, and the
      high probability of finding a variant of unknown significance (VUS) leading to a
      low signal-to-noise ratio. Next generation sequencing enables cost-efficient high
      throughput screening of a larger number of genes but at the expense of increased
      genetic noise. The yield from genetic testing is even lower in IVF in the absence
      of any suggestion of another phenotype in the index case or his/her family, and
      should be actively discouraged at this time. Future improvements in diagnostic
      utility include optimization of the use of variant-calling pipelines and shared
      databases as well as patient-specific models of disease to more accurately assign
      pathogenicity of variants. Studying "trios" of parents and the index case may
      better assess the yield of sporadic and recessive disease.

PMID- 27692677
TI  - Continuity in the midst of change!

PMID- 27692678
TI  - [Reliability of a chronic obstructive pulmonary disease diagnosis register in
      Primary Care].
AB  - INTRODUCTION/OBJECTIVE: One of main limitations in studies of COPD in health
      databases could be the low quality of the information. Our first aim was evaluate
      reliability of the registry of COPD diagnosis register in Primary Care. A
      description and comparison is also presented of the characteristics of the
      patients according to the diagnostic confirmation. MATERIAL AND METHODS: A cross
      sectional study using healthcare databases of Cantabria. A pre-selected sample of
      1,457 patients was obtained in which COPD diagnosis was specifically registered.
      COPD confirmation was classified into confirmed COPD, not confirmed-not rejected
      COPD, and diagnostic error (over-diagnosis). Descriptive and clinical
      characteristics, comorbidities, and treatments were collected in each group.
      RESULTS: COPD was confirmed in 766 patients: 52.6% (95%CI: 49.9-55.2). Prevalence
      of over-diagnosis was 7.2% (95%CI: 5.9-8.6). There were statistically significant
      gender differences. In the COPD confirmed group age, tobacco consumption and
      severity according to FEV1 was higher. An average of 1.95 bronchial exacerbations
      during the last 4years was observed among diagnostic errors. Inhaled
      corticosteroids were prescribed in 74.9% of COPD confirmed patients, and in 41.9%
      of over-diagnosed patients. CONCLUSIONS: The reliability of the COPD register was
      deficient, with only 52.6% with a confirmed diagnosis. Stable treatment for COPD
      was prescribed in all groups, highlighting the use of inhaled corticosteroids.

PMID- 27692679
TI  - Scale-up of the electrokinetic fence technology for the removal of pesticides.
      Part II: Does size matter for removal of herbicides?
AB  - This work reports results of the application of electrokinetic fence technology
      in a 32 m3 -prototype which contains soil polluted with 2,4-D and oxyfluorfen,
      focusing on the evaluation of the mechanisms that describe the removal of these
      two herbicides and comparing results to those obtained in smaller plants: a pilot
      scale mockup (175 L) and a lab-scale soil column (1 L). Results show that
      electric heating of soil (coupled with the increase in the volatility) is the key
      to explain the removal of pollutants in the largest scale facility while
      electrokinetic transport processes are the primary mechanisms that explain the
      removal of herbicides in the lab-scale plant. 2-D and 3-D maps of the temperature
      and pollutant concentrations are used in the discussion of results trying to give
      light about the mechanisms and about how the size of the setup can lead to
      different conclusions, despite the same processes are occurring in the soil.

PMID- 27692680
TI  - Scale-up of the electrokinetic fence technology for the removal of pesticides.
      Part I: Some notes about the transport of inorganic species.
AB  - This work describes the application electrokinetic fence technology to a soil
      polluted with herbicides in a large prototype containing 32 m3 of soil. It
      compares performance in this large facility with results previously obtained in a
      pilot-scale mockup (175 L) and with results obtained in a lab-scale soil column
      (1 L), all of them operated under the same driving force: an electric field of
      1.0 V cm-1. Within this wide context, this work focuses on the effect on
      inorganic species contained in soil and describes the main processes occurring in
      the prototype facility, as well as the differences observed respect to the lower
      scale plants. Thus, despite the same processes can be described in the three
      plants, important differences are observed in the evolution of the current
      intensity, moisture and conductivity. They can be related to the less important
      electroosmotic fluxes in the larger facilities and to the very different
      distances between electrodes, which lead to very different distribution of
      species and even to a very different evolution of the resulting current
      intensity. 2-D maps of the main species at different relevant moments of the test
      are discussed and important information is drawn from them. Ions depletion from
      soil appears as a very important problem which should be prevented if the effect
      of natural bioremediation and/or phytoremediation on the removal or organics aims
      to be accounted.

PMID- 27692681
TI  - Infrequent cardiac manifestations of sarcoidosis.
AB  - Cardiac sarcoidosis (CS) is found in 2-7% of patients with systemic sarcoidosis
      (SS). Its diagnosis and treatment is challenging, notwithstanding the poor
      prognosis and treatment. Hereby, we present a case of systemic sarcoidosis with
      rare cardiac manifestations of severe mitral incompetence and large coronary
      aneurysm in a previously healthy woman. She underwent successful mitral valve
      replacement and coronary artery bypass surgery and was maintained on low dose
      glucocorticoid therapy.

PMID- 27692682
TI  - Mobile Communication Devices, Ambient Noise, and Acoustic Voice Measures.
AB  - OBJECTIVES: The ability to move with mobile communication devices (MCDs; ie,
      smartphones and tablet computers) may induce differences in microphone-to-mouth
      positioning and use in noise-packed environments, and thus influence reliability
      of acoustic voice measurements. This study investigated differences in various
      acoustic voice measures between six recording equipments in backgrounds with low
      and increasing noise levels. METHODS: One chain of continuous speech and
      sustained vowel from 50 subjects with voice disorders (all separated by silence
      intervals) was radiated and re-recorded in an anechoic chamber with five MCDs and
      one high-quality recording system. These recordings were acquired in one
      condition without ambient noise and in four conditions with increased ambient
      noise. A total of 10 acoustic voice markers were obtained in the program Praat.
      Differences between MCDs and noise condition were assessed with Friedman repeated
      measures test and posthoc Wilcoxon signed-rank tests, both for related samples,
      after Bonferroni correction. RESULTS: (1) Except median fundamental frequency and
      seven nonsignificant differences, MCD samples have significantly higher acoustic
      markers than clinical reference samples in minimal environmental noise. (2)
      Except median fundamental frequency, jitter local, and jitter rap, all acoustic
      measures on samples recorded with the reference system experienced significant
      influence from room noise levels. CONCLUSIONS: Fundamental frequency is resistant
      to recording system, environmental noise, and their combination. All other
      measures, however, were impacted by both recording system and noise condition,
      and especially by their combination, often already in the reference/baseline
      condition without added ambient noise. Caution is therefore warranted regarding
      implementation of MCDs as clinical recording tools, particularly when applied for
      treatment outcomes assessments.

PMID- 27692684
TI  - Decompression in endocrine orbitopathy with a navigated piezosurgical bone
      grinder.

PMID- 27692685
TI  - Editorial Comment.

PMID- 27692683
TI  - The Effect of Combined Out-of-Hospital Hypotension and Hypoxia on Mortality in
      Major Traumatic Brain Injury.
AB  - STUDY OBJECTIVE: Survival is significantly reduced by either hypotension or
      hypoxia during the out-of-hospital management of major traumatic brain injury.
      However, only a handful of small studies have investigated the influence of the
      combination of both hypotension and hypoxia occurring together. In patients with
      major traumatic brain injury, we evaluate the associations between mortality and
      out-of-hospital hypotension and hypoxia separately and in combination. METHODS:
      All moderate or severe traumatic brain injury cases in the preimplementation
      cohort of the Excellence in Prehospital Injury Care study (a statewide,
      before/after, controlled study of the effect of implementing the out-of-hospital
      traumatic brain injury treatment guidelines) from January 1, 2007, to March 31,
      2014, were evaluated (exclusions: <10 years, out-of-hospital oxygen saturation
      <=10%, and out-of-hospital systolic blood pressure <40 or >200 mm Hg). The
      relationship between mortality and hypotension (systolic blood pressure <90 mm
      Hg) or hypoxia (saturation <90%) was assessed with multivariable logistic
      regression, controlling for Injury Severity Score, head region severity, injury
      type (blunt versus penetrating), age, sex, race, ethnicity, payer, interhospital
      transfer, and trauma center. RESULTS: Among the 13,151 patients who met inclusion
      criteria (median age 45 years; 68.6% men), 11,545 (87.8%) had neither hypotension
      nor hypoxia, 604 (4.6%) had hypotension only, 790 (6.0%) had hypoxia only, and
      212 (1.6%) had both hypotension and hypoxia. Mortality for the 4 study cohorts
      was 5.6%, 20.7%, 28.1%, and 43.9%, respectively. The crude and adjusted odds
      ratios for death within the cohorts, using the patients with neither hypotension
      nor hypoxia as the reference, were 4.4 and 2.5, 6.6 and 3.0, and 13.2 and 6.1,
      respectively. Evaluation for an interaction between hypotension and hypoxia
      revealed that the effects were additive on the log odds of death. CONCLUSION: In
      this statewide analysis of major traumatic brain injury, combined out-of-hospital
      hypotension and hypoxia were associated with significantly increased mortality.
      This effect on survival persisted even after controlling for multiple potential
      confounders. In fact, the adjusted odds of death for patients with both
      hypotension and hypoxia were more than 2 times greater than for those with either
      hypotension or hypoxia alone. These findings seem supportive of the emphasis on
      aggressive prevention and treatment of hypotension and hypoxia reflected in the
      current emergency medical services traumatic brain injury treatment guidelines
      but clearly reveal the need for further study to determine their influence on
      outcome.

PMID- 27692687
TI  - Corrigendum to "Beta-caryophyllene modulates expression of stress response genes
      and mediates longevity in Caenorhabditis elegans" [Exp. Gerontol. 57 (2014) 81
      95].

PMID- 27692686
TI  - The effects of N-acetyl cysteine on oxidative stress among patients with pre
      eclampsia.

PMID- 27692688
TI  - Prevalence of high on-treatment platelet reactivity in patients after
      percutaneous coronary intervention.

PMID- 27692689
TI  - [Psoriasis and psoriatic arthritis induced by nivolumab (Opdivo(r))].

PMID- 27692690
TI  - [Allergic contact dermatitis to Mirvaso(r) (brimonidine tartrate)].

PMID- 27692691
TI  - Targeted methylation sequencing reveals dysregulated Wnt signaling in Parkinson
      disease.
AB  - Parkinson disease (PD) is a progressive neurodegenerative movement disorder. Both
      environmental and genetic factors play important roles in PD etiology. A number
      of environmental toxins cause parkinsonism in human and animal models. Genetic
      studies of rare early onset familial PD cases resulted in identification of
      disease-linked mutations in multiple genes. Nevertheless, the potential
      interaction between environment and genetics in PD pathogenesis remains largely
      unknown. We hypothesized that environmental factors induce abnormal epigenetic
      regulation that is involved in the pathogenesis of both familial and sporadic PD.
      We determined the global methylation status of 80,000-110,000 CpG sites in each
      of the five sporadic PD patient brains and five age and postmodern interval
      matched control brains utilizing bisulfite padlock sequencing. Multiple genes
      involved in neurogenesis, particularly the ones in the Wnt signaling pathway,
      were hypermethylated in PD brains compared to their matched control brains.
      Consistent with the DNA methylation changes, marked reduction of protein
      expression was observed for four Wnt and neurogenesis related genes (FOXC1,
      NEURG2, SPRY1, and CTNNB1) in midbrain dopaminergic (DA) neurons of PD. The
      treatment of low concentration of 1-methyl-4-phenylpyridinium (MPP+) for cells
      resulted in downregulation of Wnt related genes. The study revealed an important
      link between the epigenetic disregulation of Wnt signaling and the pathogenesis
      and progression of PD.

PMID- 27692693
TI  - Clinical outcomes of anatomic, all-inside, anterior cruciate ligament (ACL)
      reconstruction.
AB  - BACKGROUND: This paper reports the outcomes of patients undergoing ACL
      reconstruction using a TransLateral single bundle, all-inside hamstring technique
      at a minimum of two year follow-up. METHODS: The semitendinosus alone is
      harvested, quadrupled and attached in series to two adjustable suspensory
      fixation devices. Femoral and tibial sockets are produced using a retrograde
      drill. The graft is deployed, fixed and tensioned on both tibia and femur.
      Patients were evaluated preoperatively using the KOOS, Lysholm and Tegner scores
      and at six, 12 and 24months postoperatively. Objective assessment of knee laxity
      was performed using the KT-1000 along with goniometric measurement of range or
      motion. RESULTS: One hundred and eight patients, mean age 30.9years (range 15 to
      61) were included. Mean follow-up 49.8months (range 30-66). The mean increase in
      KOOS at two years was 30.3 points; Lysholm, 33.1 points; Tegner Activity scale,
      2.0 levels. These were all statistically significant (p<0.001). Range of motion
      in the reconstructed knee approximated the uninjured knee by 12months and was
      restored by two years. KT-1000 showed significant reduction in side-side
      difference to no more than 2.4mm at all postoperative time points (p<0.001). Re
      rupture rate in this series was 6.5%, all following episodes of significant
      additional postoperative trauma to the knee. CONCLUSIONS: TransLateral all-inside
      ACL reconstruction demonstrates good medium term subjective and objective
      outcomes with a low complication and failure rate.

PMID- 27692692
TI  - Recommendations on the use of deep neuromuscular blockade by anaesthesiologists
      and surgeons. AQUILES (Anestesia QUIrurgica para Lograr Eficiencia y Seguridad)
      Consensus.
AB  - INTRODUCTION: Neuromuscular blockade enables airway management, ventilation and
      surgical procedures. However there is no national consensus on its routine
      clinical use. The objective was to establish the degree of agreement among
      anaesthesiologists and general surgeons on the clinical use of neuromuscular
      blockade in order to make recommendations to improve its use during surgical
      procedures. METHODS: Multidisciplinary consensus study in Spain.
      Anaesthesiologists experts in neuromuscular blockade management (n=65) and
      general surgeons (n=36) were included. Delphi methodology was selected. A survey
      with 17 final questions developed by a dedicated scientific committee was
      designed. The experts answered the successive questions in two waves. The survey
      included questions on: type of surgery, type of patient, benefits/harm during and
      after surgery, impact of objective neuromuscular monitoring and use of reversal
      drugs, viability of a multidisciplinary and efficient approach to the whole
      surgical procedure, focussing on the level of neuromuscular blockade. RESULTS:
      Five recommendations were agreed: 1) deep neuromuscular blockade is very
      appropriate for abdominal surgery (degree of agreement 94.1%), 2) and in obese
      patients (76.2%); 3) deep neuromuscular blockade maintenance until end of surgery
      might be beneficial in terms of clinical aspects, such as as immobility or better
      surgical access (86.1 to 72.3%); 4) quantitative monitoring and reversal drugs
      availability is recommended (89.1%); finally 5) anaesthesiologists/surgeons joint
      protocols are recommended. CONCLUSIONS: Collaboration among anaesthesiologists
      and surgeons has enabled some general recommendations to be established on deep
      neuromuscular blockade use during abdominal surgery.

PMID- 27692694
TI  - SGO Health Policy and Socioeconomic Committee: Current and Future Efforts of the
      Coding and Reimbursement Taskforce and the Policy, Quality and Outcomes
      Taskforce.

PMID- 27692696
TI  - De Ritis Ratio (AST/ALT) as a Significant Prognostic Factor in Patients With
      Upper Tract Urothelial Cancer Treated With Surgery.
AB  - INTRODUCTION: We investigated the clinical prognostic value of preoperative De
      Ritis ratio (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) on
      postsurgical survival outcomes in patients with upper tract urothelial cancer
      (UTUC). PATIENTS AND METHODS: We retrospectively analyzed the data of 623
      patients who underwent radical nephrouretectomy for UTUC. Multivariate regression
      tests were performed to identify possible associations between adverse pathologic
      events and AST/ALT. The risk of postoperative progression and survival were
      tested using Kaplan-Meier analyses and Cox proportional hazards models. RESULTS:
      According to the receiver operator characteristic curve of AST/ALT for cancer
      specific mortality, patients with AST/ALT value >=1.5 were regarded as the high
      AST/ALT group, and the remaining patients formed the low AST/ALT group. In Kaplan
      Meier analyses, the high AST/ALT group showed worse progression-free survival
      (PFS), cancer-specific survival (CSS), and overall survival (all P < .001).
      Elevated AST/ALT was associated with higher T stage (hazard ratio [HR], 1.577;
      95% confidence interval [CI], 1.077-2.311; P = .033) and higher cellular grade
      (HR, 1.538; 95% CI, 1.034-2.287; P = .041) in multivariate regression tests. In
      multivariate Cox analyses, high AST/ALT was revealed as an independent predictor
      of PFS (HR, 2.335; 95% CI, 1.633-3.340; P < .001), CSS (HR, 2.550; 1.689-3.851; P
      < .001), and overall survival (HR, 2.069; 95% CI, 1.409-3.038; P < .001).
      CONCLUSION: Elevated preoperative AST/ALT was a significant predictor of worse
      postoperative survival in patients surgically treated for UTUC. Further large
      prospective studies are needed for better understanding of the prognostic value
      of preoperative AST/ALT.

PMID- 27692695
TI  - Adjunctive 5-Hydroxytryptophan Slow-Release for Treatment-Resistant Depression:
      Clinical and Preclinical Rationale.
AB  - Serotonin transporter (SERT) inhibitors treat depression by elevating brain
      extracellular 5-hydroxytryptamine (5-HTExt). However, only one-third of patients
      respond adequately. Treatment-resistant depression (TRD) is a major unmet need.
      Interestingly, elevating 5-HTExt beyond what is achieved by a SERT inhibitor
      appears to treat TRD. Adjunctive administration of 5-hydroxytryptophan (5-HTP)
      safely elevates 5-HTExt beyond the SERT inhibitor effect in humans; however, 5
      HTP cannot be a clinically viable drug because of its poor pharmacokinetics. A
      slow-release (SR) delivery mode would be predicted to overcome the
      pharmacokinetic limitations of 5-HTP, substantially enhancing the pharmacological
      action and transforming 5-HTP into a clinically viable drug. Animal studies bear
      out this prediction. Thus, adjunct 5-HTP SR could be an important new treatment
      for TRD. Here, we review the clinical and preclinical evidence for this
      treatment.

PMID- 27692697
TI  - Low-Dose Oral Ethinylestradiol With Concomitant Low-Dose Acetylsalicylic Acid for
      Advanced Castrate-Resistant Prostate Cancer.
AB  - BACKGROUND: The aim of the present study was to evaluate the activity and
      tolerability of low-dose oral ethinylestradiol (EE) and luteinizing hormone
      releasing hormone analogue with concomitant low-dose acetylsalicylic acid (ASA)
      as a thromboprophylactic agent for advanced castrate-resistant prostate cancer
      (CRPC). PATIENTS AND METHODS: The patients received an EE dose of 150 MUg daily
      (50 MUg 3 times daily) and an ASA dose of 100 mg once daily. The primary endpoint
      was the prostate-specific antigen response. RESULTS: A total of 32 patients were
      enrolled. A PSA response was observed in 19 patients (59.3%; 95% confidence
      interval [CI], 41%-76%). The median progression-free survival was 9.4 months (95%
      CI, 6.5-14.1 months). The treatment was generally well tolerated and no grade 3-4
      toxicity was observed. Only 1 patient interrupted EE because of a cardiac event
      and 1 patient experienced grade 2 nausea and vomiting. No major bleeding
      occurred. CONCLUSION: Low-dose EE with concomitant low-dose ASA is safe, showing
      potential activity in patients with advanced CRPC, and should be investigated
      further.

PMID- 27692698
TI  - Corrigendum to "Aminophylline increases respiratory muscle activity during
      hypercapnia in humans" [Pulm. Pharmacol. Ther. (2015) 96-101].

PMID- 27692700
TI  - Unilateral Pulmonary Edema Due to Leaflet Fracture of a Duromedics Edwards
      Bileaflet Mitral Valve.

PMID- 27692699
TI  - Empirically derived patterns of psychiatric symptoms in youth: A latent profile
      analysis.
AB  - BACKGROUND: By conceptualizing domains of behavior transdiagnostically, the
      National Institute of Mental Health Research Domain Criteria (NIMH RDoC)
      initiative facilitates new ways of studying psychiatric symptoms. In this study,
      latent profile analysis (LPA) was used to empirically derive classes or patterns
      of psychiatric symptoms in youth that transect traditional nosologic boundaries.
      METHODS: Data were drawn from 509 children and adolescents (ages 7-18 years; mean
      age =12.9 years; 54% male) who were evaluated in the NIMH Emotion and Development
      Branch and were heterogeneous with respect to presenting diagnoses and symptoms.
      Youth and/or their parents completed measures of several core symptom dimensions:
      irritability, anxiety, depression, and attention deficit hyperactivity disorder
      (ADHD). LPA was used to parse response patterns into distinct classes, based on
      the levels of, and interrelations among, scores on the different measures.
      RESULTS: Five classes emerged: low levels of symptomatology (52% of sample);
      anxiety and mild depressive symptoms (17%); parent-reported irritability and ADHD
      (16%); irritability and mixed comorbid symptoms (10%); and high levels of
      irritability, anxiety, depression, and ADHD (5%). Importantly, these latent
      classes cut across informants and the clinical conditions for which youth were
      initially evaluated. Further, the classes characterized by irritability exhibited
      the poorest overall functioning. LIMITATIONS: These data were cross-sectional.
      Examination of external validators, including neurobiological correlates and
      symptom course, is warranted. CONCLUSIONS: Results inform our understanding of
      the structure of psychiatric symptoms in youth and suggest new ways to
      operationalize psychopathology and examine it in relation to neurobiology.

PMID- 27692701
TI  - Quality of Life in Relation to Length of Intensive Care Unit Stay After Cardiac
      Surgery.

PMID- 27692702
TI  - Pulmonary Artery Catheter Use During Cardiac Surgery in the United States.

PMID- 27692703
TI  - Targeted Bleeding Management Reduces the Requirements for Blood Component Therapy
      in Lung Transplant Recipients.
AB  - OBJECTIVE: Lung transplantation is associated with high rates of bleeding and
      frequent blood transfusion. The authors aimed to determine if point-of-care
      coagulation testing (POCCT) reduced transfusion requirements. DESIGN, SETTINGS,
      AND PARTICIPANTS: A before-and-after cohort analysis conducted at a single
      tertiary referral center. Ninety-three sequential adult patients between January
      2010 and January 2014 undergoing isolated lung transplant without preoperative
      extracorporeal support were analyzed. INTERVENTION: ROTEM and multi-plate POCCT
      were introduced on July 1, 2012, with an associated algorithm based on the
      results. MEASUREMENTS AND MAIN RESULTS: Statistically significant decreases in
      the proportion of patients receiving PRBCs (87% v 65%; p = 0.015), FFP (72% v
      30%; p<0.0001) and platelets (70% v 37%; p = 0.002) were found after the
      intervention. There were small decreases in median chest tube blood loss at 2
      hours (300 mLs v 215 mLs; p = 0.03) and 4 hours (440 mLs v 350 mLs; p = 0.050)
      but not at 12 hours postoperatively. There were no changes in reoperation for
      bleeding (9% v 4%; p = 0.158) or in-hospital mortality (6% v 2%; p = 0.617). The
      cost of blood products administered decreased from a median of $3,935.00 to
      $991.00 (p<0.001). CONCLUSIONS: Use of POCCT in lung-transplant surgery is
      associated with significant reductions in blood product use and cost. There were
      no detectable changes in outcome aside from a small decrease in early
      postoperative bleeding.

PMID- 27692704
TI  - Sevoflurane and Isoflurane-Pharmacokinetics, Hemodynamic Stability, and
      Cardioprotective Effects During Cardiopulmonary Bypass.
AB  - OBJECTIVES: This study aimed to evaluate the pharmacokinetic profiles of
      sevoflurane and isoflurane during use of minimized extracorporeal circulation to
      perform coronary artery bypass graft surgery. Furthermore, cardiovascular
      stability during bypass and the postoperative release of troponins were
      evaluated. DESIGN: Prospective, randomized study. SETTING: University hospital.
      PARTICIPANTS: The study comprised 31 adult patients undergoing coronary artery
      bypass grafting. INTERVENTIONS: The pharmacokinetic measurements of the
      concentration of the volatile anesthetics in the arterial and venous blood, air
      inlet, air outlet, and gas exhaust of the extracorporeal circulation were
      recorded. Secondary end-points were cardiovascular stability during bypass,
      amount of postoperative release of troponin, time to extubation, time to
      discharge from the intensive care unit and the hospital, and 30-day mortality.
      MEASUREMENTS AND MAIN RESULTS: Thirty patients completed the protocol. The
      pharmacokinetics of isoflurane and sevoflurane were almost identical, with a
      rapid wash-in (time to reach 50% of arterial steady state) concentration of
      0.87+/-0.97 minutes and 1.14+/-0.35 minutes for isoflurane and sevoflurane,
      respectively, and a biphasic venous elimination with a terminal half-life of
      approximately 10 minutes for both compounds. There was a correlation between the
      gas inlet and the gas exhaust of the extracorporeal circulation. No difference in
      cardiovascular stability was found. High-sensitivity troponin concentrations on
      the first postoperative morning were 0.355+/-0.312 ug/mL and 0.225+/-0.111 ug/mL
      in the isoflurane and sevoflurane groups, respectively (p = 0.147). CONCLUSIONS:
      The study found similar pharmacokinetics regarding wash-in and wash-out for
      sevoflurane and isoflurane. In addition, no difference in cardiovascular
      stability was found. The markers of cardiac damage were not different between the
      two anesthetics. Based on these data, sevoflurane and isoflurane might be used
      equivalently in patients undergoing coronary artery bypass graft surgery with
      extracorporeal circulation.

PMID- 27692705
TI  - Extreme Response to High-dose Testosterone in BRCA2- and ATM-mutated Prostate
      Cancer.

PMID- 27692706
TI  - Re: Brian I. Rini, Tanya B. Dorff, Paul Elson, et al. Active Surveillance in
      Metastatic Renal-cell Carcinoma: A Prospective, Phase 2 Trial. Lancet Oncol
      Lancet 2016;17:1317-24: Active Surveillance in Metastatic Renal Cell Carcinoma:
      Option or Exception?

PMID- 27692707
TI  - Effect of core ceramic grinding on fracture behaviour of bilayered zirconia
      veneering ceramic systems under two loading schemes.
AB  - OBJECTIVE: The aim of this in vitro study was to evaluate the effect of core
      ceramic grinding on the fracture behaviour of bilayered zirconia under two
      loading schemes. METHODS: Interfacial surfaces of sandblasted zirconia disks (A)
      were ground with 80 (B), 120 (C) and 220 (D) grit diamond discs, respectively.
      Surface roughness and topographic analysis were performed using a confocal
      scanning laser microscope (CSLM) and a scanning electron microscopy (SEM).
      Relative monoclinic content was evaluated using X-ray diffraction analysis (XRD)
      then reevaluated after simulated veneer firing. Biaxial fracture strength (sigma)
      and Weibull modulus (m) were calculated either with core in compression (subgroup
      Ac-Dc) or in tension (subgroup At-Dt). Facture surfaces were examined by SEM and
      energy dispersive X-ray spectroscopy (EDS). Maximum tensile stress at fracture
      was estimated by finite element analysis. Statistical data analysis was performed
      using Kruskal-Wallis and one-way ANOVA at a significance level of 0.05. RESULTS:
      As grit size of the diamond disc increased, zirconia surface roughness decreased
      (p<0.001). Thermal veneering treatment reversed the transformation of monoclinic
      phase observed after initial grinding. No difference in initial (p=0.519 for
      subgroups Ac-Dc) and final fracture strength (p=0.699 for subgroups Ac-Dc;
      p=0.328 for subgroups At-Dt) was found among the four groups for both loading
      schemes. While coarse grinding slightly increased final fracture strength
      reliability (m) for subgroups Ac-Dc. Two different modes of fracture were
      observed according to which material was on the bottom surface. Components of the
      liner porcelain remained on the zirconia surface after fracture for all groups.
      SIGNIFICANCE: Technician grinding changed surface topography of zirconia ceramic
      material, but was not detrimental to the bilayered system strength after veneer
      application. Coarse grinding slightly improved the fracture strength reliability
      of the bilayered system tested with core in compression. It is recommended that
      veneering porcelain be applied directly after routine lab grinding of zirconia
      ceramic, and its application on rough zirconia cores may be preferred to enhance
      bond strength.

PMID- 27692708
TI  - Characterization and comparison of the temporal dynamics of ruminal bacterial
      microbiota colonizing rice straw and alfalfa hay within ruminants.
AB  - Three ruminally cannulated Holstein cows were used to characterize the dynamics
      of bacterial colonization of rice straw and alfalfa hay and to assess the
      differences in the composition and inferred gene function of the colonized
      microbiota between these 2 forages. Nonincubated (0h) rice straw and alfalfa hay
      samples and residues in nylon bags incubated for 0.5, 2, 6, 16, and 48h were
      analyzed for dry matter and were used for DNA extraction and MiSeq (Illumina
      Inc., San Diego, CA) sequencing of the 16S rRNA gene. The microbial communities
      that colonized the air-dried and nonincubated (0h) rice straw and alfalfa hay
      were both dominated by members of the Proteobacteria (contributing toward 70.47%
      of the 16S RNA reads generated). In situ incubation of the 2 forages revealed
      major shifts in the community composition: Proteobacteria were replaced within
      30min by members belonging to the Bacteroidetes and Firmicutes, contributing
      toward 51.9 and 36.6% of the 16S rRNA reads generated, respectively. A second
      significant shift was observed after 6h of rumen incubation, when members of the
      Spirochaetes and Fibrobacteria phyla became abundant in the forage-adherent
      community. During the first 30min of rumen incubation, ~20.7 and 36.1% of the
      rice straw and alfalfa hay, respectively, were degraded, whereas little biomass
      degradation occurred between 30min and 2h after the rice straw or alfalfa hay was
      placed in the rumen. Significant differences were noted in attached bacterial
      community structure between the 2 forage groups, and the abundances of dominant
      genera Anaeroplasma, Butyrivibrio, Fibrobacter, and Prevotella were affected by
      the forage types. Real-time PCR results showed that the 16S rRNA copies of total
      bacteria attached to these 2 forages were affected by the forage types and
      incubation time, and higher numbers of attached bacterial 16S rRNA were observed
      in the alfalfa hay samples than in the rice straw from 0.5 to 16h of incubation.
      The metagenomes predicted by phylogenetic investigation of communities by
      reconstruction of unobserved states (PICRUSt) revealed that the forage types
      significantly affected 21 metabolic pathways identified in the Kyoto Encyclopedia
      of Genes and Genomes, and 33 were significantly changed over time. Collectively,
      our results reveal a difference in the dynamics of bacterial colonization and the
      inferred gene function of microbiota associated with rice straw and alfalfa hay
      within the rumen. These findings are of great importance for the targeted
      improvement of forage nutrient use efficiency in ruminants.

PMID- 27692709
TI  - Effect of a long-chain n-3 polyunsaturated fatty acid-enriched diet on adipose
      tissue lipid profiles and gene expression in Holstein dairy cows.
AB  - The objective of this study was to determine whether fish oil supplement has an
      effect on adipose tissue lipid profiles and gene expression in postpartum dairy
      cows. Holstein cows were supplemented with either long-chain n-3 polyunsaturated
      fatty acid (PUFA; protected fish oil) or control PUFA (n-6; toasted soybeans) for
      2mo after calving (n=23 per diet). These cows showed no difference in milk
      production or metabolic parameters, but exhibited a tendency toward a decrease in
      early embryo mortality rate after artificial insemination. We hypothesized that,
      in addition to this effect, modifications in adipose tissue (AT) gene expression
      and lipid profiles would occur in response to diet. Subcutaneous AT samples were
      thus collected from the dewlaps of n-3 and n-6 dairy cows at 1mo antepartum, and
      1wk, 2mo, and 5mo postpartum for the analysis of lipids and gene expression.
      Lipid profiles were obtained by matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry in both positive and negative modes. We found 37
      lipid species in the 200 to 1,200 m/z range, which differed between the n-3 and
      control groups, suggesting that the n-3 supplement affected the lipid composition
      through the enrichment of lipids integrating long-chain PUFA from fish oil
      sources: eicosapentaenoic and docosahexaenoic acid. Moreover, a decrease in
      triacylglycerolipids was observed in AT of n-3 supplemented cows. The expression
      of 44 genes involved in fatty acid metabolism and the adipokine system was
      assessed by real-time reverse-transcription PCR. Hierarchical clustering,
      according to either postpartum stage or diet, enabled us to group genes
      exhibiting similar kinetic properties during lactation or by those that varied in
      similar ways after n-3 supplementation, respectively. Among the genes exhibiting
      a dietary effect, FABP4, LIPE, CD36, and PLIN1 were overexpressed in n-3 AT
      samples compared with the control, suggesting an increase in lipolysis due to n-3
      supplementation, which was reflected on lipolytic activity at the protein level
      (i.e., protein expression of fatty acid binding protein 4, phosphorylated
      perilipin 1, and phosphorylated hormone-sensitive lipase). This increase in
      lipolysis is relevant to the decrease in triglycerides observed in these samples.
      Gene expression analyses between n-3 and control AT samples also suggested that
      the n-3 diet could modulate the secretory functions of AT, possibly by affecting
      adipokine expression; however, this has to be confirmed at the protein level.

PMID- 27692710
TI  - Invited review: Experimental design, data reporting, and sharing in support of
      animal systems modeling research.
AB  - The National Animal Nutrition Program "National Research Support Project 9"
      supports efforts in livestock nutrition, including the National Research
      Council's committees on the nutrient requirements of animals. Our objective was
      to review the status of experimentation and data reporting in animal nutrition
      literature and to provide suggestions for the advancement of animal nutrition
      research and the ongoing improvement of field-applied nutrient requirement
      models. Improved data reporting consistency and completeness represent a
      substantial opportunity to improve nutrition-related mathematical models. We
      reviewed a body of nutrition research; recorded common phrases used to describe
      diets, animals, housing, and environmental conditions; and proposed equivalent
      numerical data that could be reported. With the increasing availability of online
      supplementary material sections in journals, we developed a comprehensive
      checklist of data that should be included in publications. To continue to improve
      our research effectiveness, studies utilizing multiple research methodologies to
      address complex systems and measure multiple variables will be necessary. From
      the current body of animal nutrition literature, we identified a series of
      opportunities to integrate research focuses (nutrition, reproduction and
      genetics) to advance the development of nutrient requirement models. From our
      survey of current experimentation and data reporting in animal nutrition, we
      identified 4 key opportunities to advance animal nutrition knowledge: (1)
      coordinated experiments should be designed to employ multiple research
      methodologies; (2) systems-oriented research approaches should be encouraged and
      supported; (3) publication guidelines should be updated to encourage and support
      sharing of more complete data sets; and (4) new experiments should be more
      rapidly integrated into our knowledge bases, research programs and practical
      applications.

PMID- 27692711
TI  - Organic dairy farmers put more emphasis on production traits than conventional
      farmers.
AB  - The overall aim of this research was to characterize the preferences of Danish
      dairy farmers for improvements in breeding goal traits. The specific aims were
      (1) to investigate the presence of heterogeneity in farmers' preferences by means
      of cluster analysis, and (2) to associate these clusters with herd
      characteristics and production systems (organic or conventional). We established
      a web-based survey to characterize the preferences of farmers for improvements in
      10 traits, by means of pairwise rankings. We also collected a considerable number
      of herd characteristics. Overall, 106 organic farmers and 290 conventional
      farmers answered the survey, all with Holstein cows. The most preferred trait
      improvement was cow fertility, and the least preferred was calving difficulty. By
      means of cluster analysis, we identified 4 distinct clusters of farmers and named
      them according to the trait improvements that were most preferred: Health and
      Fertility, Production and Udder Health, Survival, and Fertility and Production.
      Some herd characteristics differed between clusters; for example, farmers in the
      Survival cluster had twice the percentage of dead cows in their herds compared
      with the other clusters, and farmers that gave the highest ranking to cow and
      heifer fertility had the lowest conception rate in their herds. This finding
      suggests that farmers prefer to improve traits that are more problematic in their
      herd. The proportion of organic and conventional farmers also differed between
      clusters; we found a higher proportion of organic farmers in the production-based
      clusters. When we analyzed organic and conventional data separately, we found
      that organic farmers ranked production traits higher than conventional farmers.
      The herds of organic farmers had lower milk yields and lower disease incidences,
      which might explain the high ranking of milk production and the low ranking of
      disease traits. This study shows that heterogeneity exists in farmers'
      preferences for improvements in breeding goal traits, that organic and
      conventional farmers differ in their preferences, and that herd characteristics
      can be linked to different farmer clusters. The results of this study could be
      used for the future development of breeding goals in Danish Holstein cows and for
      the development of customized total merit indices based on farmer preferences.

PMID- 27692712
TI  - Genetic changes of survival traits over the past 25 yr in Dutch dairy cattle.
AB  - Genetic correlations and heritabilities for survival were investigated over a
      period of 25 yr to evaluate if survival in first lactation has become a different
      trait and if this is affected by adjusting for production level. Survival after
      first calving until 12mo after calving (surv_12mo) and survival of first
      lactation (surv_1st_lac) were analyzed in Dutch black-and-white cows. The data
      set contained 1,108,745 animals for surv_12mo and 1,062,276 animals for
      surv_1st_lac, with first calving between 1989 and 2013. The trait survival as
      recorded over 25 yr was split in five 5-yr intervals to enable a multitrait
      analysis. Bivariate models using subsets of the full data set and multitrait and
      autoregressive models using the full data set were used. Survival and functional
      survival were analyzed. Functional survival was defined as survival adjusted for
      within-herd production level for 305-d yield of combined kilograms of fat and
      protein. Mean survival increased over time, whereas genetic variances and
      heritability decreased. Bivariate models yielded large standard errors on genetic
      correlations due to poor connectedness between the extreme 5-yr intervals. The
      more parsimonious models using the full data set gave nonunity genetic
      correlations. Genetic correlations for survival were below 0.90 between intervals
      separated by 1 or more 5-yr intervals. Genetic correlations for functional
      survival did not indicate that definition of survival changed (>=0.90). The
      difference in genetic correlations between survival and functional survival is
      likely explained by lower emphasis of dairy farmers on culling in first lactation
      for low yield in more recent years. This suggests that genetic evaluation for
      longevity using historical data should analyze functional survival rather than
      survival.

PMID- 27692713
TI  - Short communication: A novel method using immunomagnetic separation with a
      fluorescent nanobeads lateral flow assay for the rapid detection of low
      concentration Escherichia coli O157:H7 in raw milk.
AB  - Escherichia coli O157:H7 is an important serotype of enterohemorrhagic E. coli
      that was first identified as a human pathogen in 1982. This pathogen causes
      several serious diseases. In this study, immunomagnetic separation was coupled
      with a fluorescent nanobeads lateral flow assay to establish a sensitive and
      rapid detection method for Escherichia coli O157:H7 in raw milk. The pathogen was
      captured from raw milk by immunomagnetic separation with immunomagnetic nanobeads
      and then detected using a fluorescent nanobeads lateral flow assay. A fluorescent
      line was formed in the test line of the test strip and quantitatively detected
      using a fluorescent reader. Screening times, which included immunomagnetic
      separation and the fluorescent nanobeads lateral flow assay, were 8, 7, 6, and 5h
      when 1, 5, 25, and 125 cfu of E. coli O157:H7, respectively, were inoculated into
      25mL of raw milk. The established method could be widely applied to the rapid
      onsite detection of other pathogens to ensure food safety.

PMID- 27692714
TI  - Factors responsible for subclinical mastitis in cows caused by Staphylococcus
      chromogenes and its susceptibility to antibiotics based on bap, fnbA, eno, mecA,
      tetK, and ermA genes.
AB  - The aim of this study was to recognize selected factors of virulence determining
      the adhesion of Staphylococcus chromogenes to cows' udder tissues in subclinical
      mastitis and to evaluate the susceptibility of this pathogen to antibiotics. The
      subjects of the study were 38 isolates of Staph. chromogenes from 335 samples of
      milk from cows with subclinical coagulase-negative staphylococci mastitis.
      Somatic cell count ranged between 216,000 and 568,000/mL of milk (average
      356,000/mL of milk). We confirmed the ability to produce slime in 24 isolates
      (63.2%), and the ability to produce protease in 29 isolates (76.3%). In each
      slime-producing isolate, the bap gene was not found, and the fnbA and eno genes
      were not detected. In vitro tests showed that ceftiofur had the highest
      effectiveness against Staph. chromogenes (89.5% of susceptible isolates). Minimum
      inhibitory concentrations ranged from 0.06 to 2ug/mL for susceptible isolates.
      The minimum concentrations required to inhibit growth of 90 and 50% of the
      isolates for ceftiofur were at or below the cutoffs recommended by the Clinical
      and Laboratory Standards Institute (2 and 0.06ug/mL, respectively). A significant
      percentage of the isolates were susceptible to other beta-lactam antibiotics:
      amoxicillin with clavulanic acid (84.2%) and ampicillin (81.6%). The lowest
      effectiveness among beta-lactams was for penicillin (73.7% of susceptible
      isolates), and the minimum inhibitory concentration for penicillin ranged from
      <0.06 to 8ug/mL. None of the examined isolates had the mecA gene, but beta
      lactamase was detected in 4 isolates (10.5%). Erythromycin and oxytetracycline
      exhibited the lowest activity against Staph. chromogenes (71.1 and 63.2% of
      susceptible isolates, respectively). The genes tetK (6 isolates) and ermA (1
      isolate) were also detected.

PMID- 27692715
TI  - Evaluation of modified stainless steel surfaces targeted to reduce biofilm
      formation by common milk sporeformers.
AB  - The development of bacterial biofilms on stainless steel (SS) surfaces poses a
      great threat to the quality of milk and other dairy products as the biofilm
      embedded bacteria can survive thermal processing. Established biofilms offer
      cleaning challenges because they are resistant to most of the regular cleaning
      protocols. Sporeforming thermoduric organisms entrapped within biofilm matrix can
      also form heat-resistant spores, and may result in a long-term persistent
      contamination. The main objective of this study was to evaluate the efficacy of
      different nonfouling coatings [AMC 18 (Advanced Materials Components Express,
      Lemont, PA), Dursan (SilcoTek Corporation, Bellefonte, PA), Ni-P
      polytetrafluoroethylene (PTFE, Avtec Finishing Systems, New Hope, MN), and
      Lectrofluor 641 (General Magnaplate Corporation, Linden, NJ)] on SS plate heat
      exchanger surfaces, to resist the formation of bacterial biofilms. It was
      hypothesized that modified SS surfaces would promote a lesser amount of deposit
      buildup and bacterial adhesion as compared with the native SS surface. Vegetative
      cells of aerobic sporeformers, Geobacillus stearothermophilus (ATCC 15952),
      Bacillus licheniformis (ATCC 6634), and Bacillus sporothermodurans (DSM 10599),
      were used to study biofilm development on the modified and native SS surfaces.
      The adherence of these organisms, though influenced by surface energy and
      hydrophobicity, exhibited no apparent relation with surface roughness. The Ni-P
      PTFE coating exhibited the least bacterial attachment and milk solid deposition,
      and hence, was the most resistant to biofilm formation. Scanning electron
      microscopy, which was used to visualize the extent of biofilm formation on
      modified and native SS surfaces, also revealed lower bacterial attachment on the
      Ni-P-PTFE as compared with the native SS surface. This study thus provides
      evidence of reduced biofilm formation on the modified SS surfaces.

PMID- 27692716
TI  - Milk acidification to control the growth of Mycoplasma bovis and Salmonella
      Dublin in contaminated milk.
AB  - Bacterial contamination of milk fed to calves compromises calf health. Several
      bacterial pathogens that infect cows, including Mycoplasma bovis and Salmonella
      enterica ssp. enterica serovar Dublin, are shed in milk, providing a possible
      route of transmission to calves. Milk acidification lowers the milk pH so that it
      is unsuitable for bacterial growth and survival. The objectives of this study
      were to (1) determine the growth of M. bovis and Salmonella Dublin in milk, and
      (2) evaluate the efficacy of milk acidification using a commercially available
      acidification agent (Salstop, Impextraco, Heist-op-den-Berg, Belgium) to control
      M. bovis and Salmonella Dublin survival in milk. For the first objective, 3
      treatments and a positive control were prepared in 10 mL of milk and broth,
      respectively, and inoculated with M. bovis or Salmonella Dublin to an approximate
      concentration of 104 cfu/mL. Each treatment was retained at 5, 23, or 37 degrees
      C with the positive control at 37 degrees C. Aliquots were taken at 4, 8, 24, 28,
      32, 48, 52, and 56 h after inoculation and transferred onto agar medium in
      triplicate following a 10-fold dilution series in sterile phosphate-buffered
      saline. All plates were incubated and colonies counted. For the second objective,
      4 treatments and a positive control were prepared with 100 mL of milk and
      inoculated with M. bovis or Salmonella Dublin to an approximate concentration of
      106 cfu/mL. With the use of Salstop, treatments were adjusted to an approximate
      pH of 6, 5, 4, or 3.5. The positive control was left untreated. At 1, 2, 4, 6, 8,
      and 24 h after treatment, triplicate aliquots were taken, the pH measured, and
      then the aliquots were transferred onto agar medium and into broth for
      enrichment. Following incubation, agar colonies were counted, while broths were
      plated and incubated prior to colonies being counted. All trials were repeated.
      Mycoplasma bovis did not grow in milk, but Salmonella Dublin proliferated. The pH
      of all acidification treatments remained stable for 24 h. No viable M. bovis
      organisms were detected at 1 h of exposure to pH 3.5 and 4 or at 8 h of exposure
      to pH 5. Following 24 h of exposure to pH 6 M. bovis remained viable. No viable
      Salmonella Dublin organisms were detected at 2 and 6 h of exposure to pH 3.5 and
      4, respectively. Salmonella Dublin remained viable following 24 h of exposure to
      pH 5 and 6. These results demonstrate that milk acidification using Salstop is
      effective at eliminating viable M. bovis and Salmonella Dublin organisms in milk
      if the appropriate pH and exposure time are maintained.

PMID- 27692717
TI  - Effects of a completely pelleted diet on growth performance in Holstein heifers.
AB  - Forage neutral detergent fiber (NDF) content and particle size are important
      factors that affect rumen function. The aim of the current study was to evaluate
      the effects on rumen health, NDF digestibility, and animal performance of
      pelleting a forage-based diet. Eight Holstein heifers (age 336+/-30d, body weight
      346+/-35kg) were randomly assigned to a repeated crossover design. Animals were
      housed in tie-stalls and fed for ad libitum intake. The study included 4 periods
      of 3 wk, the first 2 wk for adaptation to the diet and the last wk for data
      collection. Diets had the same ingredients but had a different physical form:
      total mixed ration (TMR) and pellet (diameter=8mm). The physically effective NDF
      (peNDF) differed between the 2 treatments (39.8 and 11.8% of NDF in the TMR and
      pellet diets, respectively). During the trial, dry matter intake (DMI), water
      intake, rumination time, rumen temperature, and pH were evaluated daily. Fecal
      samples were collected in wk3 of each period to determine total-tract
      digestibility of the potential digestible (pd)NDF. Average daily gain and feed
      conversion ratio were calculated at the end of each period. With the pellet diet,
      DMI, DMI/body weight, and water consumption were higher. We observed no
      significant difference in average daily gain or feed conversion ratio. Rumination
      time was lower for the pellet diet than for the TMR diet (241 vs. 507min/d,
      respectively). Diet had no effect on rumen temperature or rumen pH. The total
      tract digestibility of the pdNDF was greater with the TMR diet than with the
      pellet diet (90.25 vs. 86.82% pdNDF, respectively). The results of the current
      study suggest that a complete-feed pellet diet was well accepted by the animals,
      as demonstrated by higher DMI. Rumination time was reduced with the pellet diet,
      but rumen pH was not different. The pdNDF digestibility was high for both diets,
      but significantly higher for the TMR diet. Given that animal performance was
      similar between the 2 diets, although they differed with respect to DMI and fiber
      digestion, we hypothesize that the 2 diets had different retention times, related
      to their physical form. A complete-feed pellet diet formulated to provide a
      sufficient level of NDF from forages could be fed to growing ruminants without
      apparent negative effects on rumen health and animal productivity, at least for a
      short period. More research over a longer growing period is needed before
      recommending this feeding strategy for growing heifers.

PMID- 27692718
TI  - Comparative risk assessment for new cow-level Mycobacterium avium ssp.
      paratuberculosis infections between 3 dairy production types: Organic,
      conventional, and conventional-grazing systems.
AB  - Johne's disease, a granulomatous enteritis of ruminant animals, is a hidden
      threat on dairy farms, adversely affecting animal welfare as well as herd
      productivity. Control programs in the United States advocate for specific
      management practices to temper the spread of the causal organism (Mycobacterium
      avium ssp. paratuberculosis, MAP), such as improving calving area hygiene and
      limiting introduction of replacement stock with unknown infection status. A need
      remains for direct exploration of Johne's disease prevention strategies in the
      United States with respect to production type. Alongside the growing demand for
      organic products, the safety of organic dairy practices with respect to MAP
      control is warranted. Further, conventional herds for which organic practices
      such as pasture grazing are used should be situated within the risk spectrum. We
      developed a risk assessment model using the US Voluntary Bovine Johne's Disease
      Control Program as a framework, with the goal of evaluating the risk of new cow
      level MAP infections. A total of 292 organic and conventional farms in 3 states
      were surveyed on management practices, and an overall analysis was conducted in
      which each farm was first scored on individual practices using a range of "no
      risk" to "high risk," according to the literature. The sum of all risk factors
      was then analyzed to quantify and compare the risk burden for each production
      type. Organic herds received higher overall risk scores compared with both
      conventional grazing and nongrazing subtypes. To identify which factors
      contributed to the overall increased risk for organic herds, the management
      practices were categorized and evaluated by logistic regression. We determined
      that the increased risk incurred by organic herds was predominantly due to
      decisions made in the calving area and preweaned calf group. However, although
      certain individual risk factors related to calf management are commonly involved
      in prevention strategies (e.g., cow/calf separation) and were thus included in
      the overall risk assessment, empirical evidence linking them to the spread of MAP
      is lacking. Instead, these factors are problematic when executed with other
      management decisions, leading to a hypothesized synergism of transmission risk.
      To this end, we developed a set of compound risk factors, which were also
      evaluated as outcomes in logistic regression models, with production type serving
      as the predictor of interest. Organic farms in our study were more susceptible to
      risks associated with the synergism of study variables. Notably, organic
      producers were most likely to allow calves to spend extended time with the dam,
      while also lacking a dedicated calving area. Additionally, calves in organic
      herds were more often permitted to nurse even with poor udder hygiene on farm. A
      heightened vigilance toward calving area hygiene is therefore indicated for these
      herds.

PMID- 27692719
TI  - Effects of maturity at ensiling of bermudagrass and fibrolytic enzyme application
      on the performance of early-lactation dairy cows.
AB  - The objective of this study was to examine effects of adding fibrolytic enzymes
      to diets containing bermudagrass ensiled after 4 or 7wk of regrowth on the diet
      digestibility, ruminal fermentation and performance of lactating cows, and the
      interaction of the treatments. In experiment 1, 64 Holstein cows (22+/-4d in
      milk) were assigned to an experiment with a 2*2 factorial treatment arrangement
      and a 56-d duration. Treatments were diets containing 4 or 7wk regrowth
      bermudagrass silage without or with an exogenous fibrolytic enzyme cocktail. The
      cellulase-xylanase enzyme was applied at 2.33g/kg of total mixed ration dry
      matter (DM) during mixing immediately before feeding. Experiment 2 was aimed at
      examining treatment effects on the ruminal fermentation profile. Four ruminally
      cannulated cows were assigned to the 4 treatments using a 4*4 Latin square design
      with 14-d periods. No enzyme by maturity interaction was detected for any
      measurement. Regardless of forage maturity, applying the fibrolytic enzyme did
      not affect DM intake, milk yield, apparent digestibility, feed efficiency, energy
      balance, and ruminal fermentation though it tended to increase milk lactose
      concentration (4.88 vs. 4.81%). Feeding the 4-wk diet instead of the 7-wk diet
      increased DM intake (22.4 vs. 21.3kg/d), digestibility of DM, neutral detergent
      fiber, and acid detergent fiber, and tended to increase 3.5%-fat corrected milk
      yield (47.2 vs. 44.3kg/d) and milk fat yield (1.88 vs. 1.73kg/d). Therefore,
      daily intake of net energy and secretion of milk energy were greater for the 4-wk
      diet. In addition, the 4-wk diet increased the ruminal concentrations of acetate,
      propionate, valerate, lactate, and total volatile fatty acids, and decreased
      ruminal pH, without affecting the acetate:propionate ratio. Feeding fibrolytic
      enzymes did not improve the performance of early-lactation dairy cows, but
      harvesting the forage earlier tended to improve milk production.

PMID- 27692721
TI  - Sustainable breeding objectives and possible selection response: Finding the
      balance between economics and breeders' preferences.
AB  - To optimize breeding objectives of Fleckvieh and Brown Swiss cattle, economic
      values were re-estimated using updated prices, costs, and population parameters.
      Subsequently, the expected selection responses for the total merit index (TMI)
      were calculated using previous and newly derived economic values. The responses
      were compared for alternative scenarios that consider breeders' preferences. A
      dairy herd with milk production, bull fattening, and rearing of replacement stock
      was modeled. The economic value of a trait was derived by calculating the
      difference in herd profit before and after genetic improvement. Economic values
      for each trait were derived while keeping all other traits constant. The traits
      considered were dairy, beef, and fitness traits, the latter including direct
      health traits. The calculation of the TMI and the expected selection responses
      was done using selection index methodology with estimated breeding values instead
      of phenotypic deviations. For the scenario representing the situation up to 2016,
      all traits included in the TMI were considered with their respective economic
      values before the update. Selection response was also calculated for newly
      derived economic values and some alternative scenarios, including the new trait
      vitality index (subindex comprising stillbirth and rearing losses). For
      Fleckvieh, the relative economic value for the trait groups milk, beef, and
      fitness were 38, 16, and 46%, respectively, up to 2016, and 39, 13, and 48%,
      respectively, for the newly derived economic values. Approximately the same
      selection response may be expected for the milk trait group, whereas the new
      weightings resulted in a substantially decreased response in beef traits. Within
      the fitness block, all traits, with the exception of fertility, showed a positive
      selection response. For Brown Swiss, the relative economic values for the main
      trait groups milk, beef, and fitness were 48, 5, and 47% before 2016,
      respectively, whereas for the newly derived scenario they were 40, 14, and 39%.
      For both Brown Swiss and Fleckvieh, the fertility complex was expected to further
      deteriorate, whereas all other expected selection responses for fitness traits
      were positive. Several additional and alternative scenarios were calculated as a
      basis for discussion with breeders. A decision was made to implement TMI with
      relative economic values for milk, beef, and fitness with 38, 18, and 44% for
      Fleckvieh and 50, 5, and 45% for Brown Swiss, respectively. In both breeds, no
      positive expected selection response was predicted for fertility, although this
      trait complex received a markedly higher weight than that derived economically.
      An even higher weight for fertility could not be agreed on due to the effect on
      selection response of other traits. Hence, breeders decided to direct more
      attention toward the preselection of bulls with regard to fertility.

PMID- 27692720
TI  - Short communication: Relationship of activity and rumination to abundance of pest
      flies among organically certified cows fed 3 levels of concentrate.
AB  - The objectives of this study were to evaluate activity, rumination time, and
      their association with 3 kinds of pasture flies for organic dairy cows (n=57) fed
      3 grain supplementation strategies during the grazing season from May to
      September 2013. Cows were assigned to 1 of 3 replicate supplementation groups:
      (1) no corn-grain supplementation (100% pasture, PAS, n=19); (2) low corn-grain
      (2.72kg/cow per day, LG, n=19); and (3) high corn-grain (5.44kg/cow per day, HG,
      n=19). Cows calved during 2 seasons (fall and spring) at the University of
      Minnesota West Central Research and Outreach Center, Morris, from October to
      December 2012 and March to May 2013. Supplement (corn-grain and minerals) was fed
      in a total mixed ration of corn silage and alfalfa silage, and at least 30% of
      diet dry matter intake for LG and HG cows consisted of pasture. Activity and
      rumination time (daily and 2-h blocks of time) were monitored electronically
      using HR-LD tags (SCR Engineers Ltd., Netanya, Israel) for 125d. Activity (cow
      body movement and head movement) was reported in activity units from SCR DataFlow
      II software, and rumination times were reported in minutes per day. PROC HPMIXED
      in SAS (SAS Institute Inc., Cary, NC) was used for statistical analysis, and
      independent variables were season of calving (fall or spring), month of grazing
      (June to September), supplementation group, and interactions of month of grazing
      and supplementation group. Replicate was a random effect with repeated measures.
      Daily activity was higher for PAS cows (1,138 activity units) than for HG cows
      (1,001 activity units), and LG cows (1,019 activity units). Daily activity was
      highest in July (1,258 activity units) and lowest in September (819 activity
      units). Rumination was not different for PAS (397min/d), LG (384min/d), or HG
      (370min/d) cows. Daily rumination was greater in September (402min/d) than in
      July (361min/d). Daily activity increased rapidly between 0600-0800h and 1600
      1800h. From 1800 to 2000h, cows had a rapid decline in activity until 0600h the
      next day. All supplementation groups had the greatest rumination activity from
      0200 to 0400h and the least between 1000 and 1200h. Greater activity of cows on a
      herd basis was moderately correlated with increased fly populations. Monthly
      activity patterns of grazing cows were associated with fly populations on cows.

PMID- 27692722
TI  - Genotype by environment interaction for activity-based estrus traits in relation
      to production level for Danish Holstein.
AB  - The objective of this study was to investigate whether genotype by environment
      interaction exists for female fertility traits and production of energy-corrected
      milk at 70d in milk (ECM70). Fertility traits considered were the activity-based
      estrus traits interval from calving to first high activity (CFHA), duration of
      high activity episode (DHA), as an indicator for first estrus duration, and
      strength of high activity episode (SHA), as an indicator for first estrus
      strength. The physical activity traits were derived from electronic activity tags
      for 11,522 first-parity cows housed in 125 commercial dairy herds. Data were
      analyzed using a univariate random regression animal model (URRM), by regressing
      the phenotypic performance on the average herd ECM70 as an environmental
      gradient. Furthermore, the genetic correlations between CFHA and ECM70 as a
      function of production level were estimated using a bivariate random regression
      animal model (BRRM). For all traits, heterogeneity of additive genetic variances
      and heritability estimates was observed. The heritability estimate for CFHA
      decreased from 0.25 to 0.10 with increasing production level and the heritability
      estimate for ECM70 decreased from 0.35 to 0.15 with increasing production level
      using URRM. The genetic correlation of the same trait in low and high production
      levels was around 0.74 for CFHA and 0.80 for ECM70 using URRM, but when data were
      analyzed using the multiple-trait analysis (MT), genetic correlation estimates
      between low and high production levels were not significantly different from
      unity. Furthermore, the genetic correlation of SHA between low and high
      production level was 0.22 using URRM, but the corresponding correlation estimate
      had large standard error when data were analyzed using MT. The genetic
      correlation between CFHA and ECM70 as a function of production environment was
      weak but unfavorable and decreased slightly from 0.09 to 0.04 with increasing
      production level using BRRM. Moreover, the same trend was observed when the data
      were analyzed using MT where the genetic correlation between CFHA and ECM70 in
      the low production environment was 0.29 compared with -0.13 in the high
      production environment, but these estimates had large standard errors. In
      conclusion, regardless of the trait used, in relation to average herd ECM70
      production, the results indicated no clear evidence of strong genotype by
      environment interaction that would cause significant re-ranking of sires between
      low and high production environments.

PMID- 27692723
TI  - Associations of high and low milk protein concentrations with energy allocation,
      milk production, and concentrations of blood plasma metabolites and hormones in
      Holstein-Friesian cows.
AB  - A positive association between milk protein concentration (MPC) and reproductive
      performance in dairy cows has been shown in several studies globally. This
      association may positively influence farm productivity and profitability,
      particularly in seasonally calving, pasture-based herds. However, the differences
      in milk production and energy allocation, physical characteristics, and blood
      plasma nutrient status between cows with differing MPC have not been examined,
      and the underlying mechanisms responsible for the association remain undefined.
      The objective of this study was to examine associations between MPC and nutrient
      partitioning in primiparous Holstein-Friesian cows managed under pasture-based
      dairying conditions, and to identify differences that may indicate the underlying
      mechanisms. Data were collected from 85 cows at regular intervals during the
      early part of the 2013 to 2014 seasonal lactation, including daily milk yield,
      weekly milk composition, weekly body condition score measurements, as well as
      weekly blood plasma metabolite and hormone concentrations. Cows were
      retrospectively separated into quartiles based on their average MPC during the
      first 120d of lactation, and comparisons were made between cows within the
      highest (high; 3.22 to 3.40%) and the lowest (low; 2.87 to 3.00%) MPC quartiles.
      The high-MPC cows had lower daily milk yields, yet did not differ in the daily
      yields of milk solids (protein + fat) compared with the low-MPC cows. After
      parturition, the high-MPC cows had greater blood plasma concentrations of
      glucose, insulin, insulin-like growth factor-1 and leptin compared with the low
      MPC cows and maintained their body condition score, despite no differences in
      these variables prepartum. These results indicate an increased partitioning of
      nutrients toward milk synthesis at the expense of body condition for cows in the
      low MPC quartile. However, average daily energy outputs in milk were similar in
      the high- and low-MPC cows. The high-MPC cows calved 12d earlier in the seasonal
      calving period, reflecting superior reproductive performance when cows in this
      quartile were 15mo of age. These results suggest that at least part, but not all,
      of the reported associations between MPC and dairy cow fertility are related to
      nutrient status during early lactation. Further research is required to
      understand and use the association.

PMID- 27692724
TI  - The Impact of Language on Voice: An LTAS Study.
AB  - OBJECTIVES: The present study investigates possible differences in sound
      characteristics associated with Farsi and Qashqai produced by Farsi-Qashqai
      bilinguals. STUDY DESIGN: This is a descriptive-analytical and cross-sectional
      study. METHODS: Thirty-two Farsi-Qashqai bilinguals (16 men and 16 women)
      participated in the study. Mean spectral energy (MSE) and spectral tilt (ST)
      obtained from long-term average speech spectra were extracted from continuous
      speech samples of Farsi-Qashqai bilingual speakers. MSE and ST were calculated
      using Praat and then compared between Farsi and Turkish. RESULTS: Results showed
      that bilingual speakers had higher MSE and lower ST in Farsi than in Turkish.
      CONCLUSIONS: Findings show that even with the same phonatory apparatus, spoken
      language affects the speaker's voice quality.

PMID- 27692725
TI  - Impact of Cricothyroid Muscle Contraction on Vocal Fold Vibration: Experimental
      Study with High-Speed Videoendoscopy.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of cricothyroid
      muscle contraction on vocal fold vibration, as evaluated with high-speed
      videoendoscopy, and to identify one or more aspects of vocal fold vibration that
      could be used as an irrefutable indicator of unilateral cricothyroid muscle
      paralysis. STUDY DESIGN: This was an experimental study employing excised human
      larynges. METHODS: Twenty freshly excised human larynges were evaluated during
      artificially produced vibration. Each larynx was assessed in three situations:
      bilateral cricothyroid muscle contraction, unilateral cricothyroid muscle
      contraction, and no contraction of either cricothyroid muscle. The following
      parameters were evaluated by high-speed videoendoscopy: fundamental frequency,
      periodicity, amplitude of vocal fold vibration, and phase symmetry between the
      vocal folds. RESULTS: Although neither unilateral nor bilateral cricothyroid
      muscle contraction altered the periodicity of vibration or the occurrence of
      phase asymmetry, there was a significant decrease in fundamental frequency in
      parallel with decreasing longitudinal tension. We also found an increase in
      vibration amplitude of right and left vocal folds, which were similar in terms of
      their behavior for this parameter in the various situations studied. CONCLUSION:
      Our results suggest that differences in vibration amplitude and phase symmetry
      between vocal folds are not reliable indicators of unilateral cricothyroid muscle
      paralysis.

PMID- 27692726
TI  - Critical Limb Ischemia: An Expert Statement.
AB  - Critical limb ischemia (CLI), the most advanced form of peripheral artery
      disease, is associated with significant morbidity, mortality, and health care
      resource utilization. It is also associated with physical, as well as
      psychosocial, consequences such as amputation and depression. Importantly, after
      a major amputation, patients are at heightened risk of amputation on the
      contralateral leg. However, despite the technological advances to manage CLI with
      minimally invasive technologies, this condition often remains untreated, with
      significant disparities in revascularization and amputation rates according to
      race, socioeconomic status, and geographic region. Care remains disparate across
      medical specialties in this rapidly evolving field. Many challenges persist,
      including appropriate reimbursement for treating complex patients with difficult
      anatomy. This paper provides a comprehensive summary that includes diagnostic
      assessment and analysis, endovascular versus open surgical treatment,
      regenerative and adjunctive therapies, and other important aspects of CLI.

PMID- 27692727
TI  - Can TAVR Make Me Smarter?

PMID- 27692728
TI  - Serial Changes in Cognitive Function Following Transcatheter Aortic Valve
      Replacement.
AB  - BACKGROUND: Data regarding the mid- to long-term cognitive trajectory of
      transcatheter aortic valve (TAVR) recipients are scarce. OBJECTIVES: Changes in
      global cognition and specific cognitive domains up to 1 year post-TAVR were
      evaluated. METHODS: Fifty-one patients (median age 80.0 [interquartile range:
      72.0 to 85.0] years; 37% women) underwent TAVR and prospective assessment of
      cognitive function using the Montreal Cognitive Assessment (MoCA) at baseline,
      short-term (30 days), and 1 year post-TAVR. Processing speed and executive
      cognitive functions were further evaluated with the digit-symbol substitution
      test (DSST), Trail Making Tests (TMT), and verbal fluency tests at the same time
      points. Cognitive decline (CD) was determined by changes in mean scores and as a
      rate using practice-corrected reliable change index (RCI). RESULTS: The baseline
      mean total MoCA score was 22.71 +/- 3.84. Twenty patients (39.2%) were considered
      cognitively impaired using a cutoff of <23 of 30 points. Mean total MoCA score
      improved at short-term post-TAVR and remained stable at 1 year (p = 0.022). On
      the basis of the RCI of total MoCA score, 4 patients (7.8%) presented with short
      term CD, which persisted at 1 year in 1 patient (2.0%). Four patients (7.8%)
      exhibited cognitive improvement at 1 year, increasing to 15% among those with
      baseline cognitive impairment. No significant changes were observed over time in
      the mean DSST, TMT, and verbal fluency test scores. On the basis of the RCI, 10
      of 40 patients (25%) presented with a reduction in performance of at least 1 test
      at 30 days that persisted at 1 year in 4 patients (10%). CONCLUSIONS: TAVR was
      associated with global improvement in cognitive status, more pronounced among
      those with cognitive impairment pre-TAVR. However, early decline in some complex
      cognitive functions was observed in one-quarter of TAVR recipients, persisting at
      1 year in 10% of patients.

PMID- 27692729
TI  - Midkine is up-regulated in both cancerous and inflamed bowel, reflecting lymph
      node metastasis in colorectal cancer and clinical activity of ulcerative colitis.
AB  - Midkine is a multifunctional cytokine and growth factor displaying
      proinflammatory and pro-tumorigenic activity. Its association with bowel diseases
      has not been fully elucidated. Our purpose was to delineate midkine expression
      pattern by RT-qPCR in inflamed/cancerous bowel (n=208) and whole blood (n=150) in
      colorectal cancer (CRC), Crohn's disease (CD), and ulcerative colitis (UC) and to
      evaluate midkine dynamics in early postoperative period following colorectal
      surgery. The expression of midkine was significantly up-regulated in stage III
      CRC and independently associated with lymph node metastasis. The expression of
      midkine in whole blood was up-regulated solely in N1 CRC. Midkine expression in
      cancer-free tissue (CRC) was also elevated and dependent on CRC advancement. In
      IBD, inflammation increased the bowel expression of midkine solely in UC, in a
      manner proportional to the disease clinical activity. Large and small bowel
      differed with respect to the expression of midkine in quiescent tissue (higher in
      small bowel) and to its correlation pattern with chemokines (in a large bowel)
      and angiogenic factors and cell cycle regulators (in a small bowel). Circulating
      midkine and its expression in whole blood dropped directly following colorectal
      surgery; however, the concentration of midkine in serum was restored on
      postoperative day three. Midkine is involved in bowel inflammation in UC and
      lymph node metastasis in CRC, rendering midkine an attractive target for their
      treatment. Owing to midkine elevation in early postoperative period and its
      overexpression in tumor-adjacent tissue, targeting midkine might be considered
      also as a prevention of CRC recurrence following curative tumor resection.

PMID- 27692730
TI  - [Urinary incontinence and sexual dysfunction after treatment of localized
      prostate cancer: Results from a population aged less than 65years old].
AB  - INTRODUCTION: An increasing number of patients with prostate cancer (PC) are
      diagnosed and treated. The aim of this study was to investigate urinary
      incontinence (UI) and sexual dysfunction (SD) two years after treatment for
      localized prostate cancer (PC). METHODS: This study followed all cases of
      localized PC diagnosed between 2008 and 2009 in men aged<=65years old and still
      alive two years after treatment. In total, 437 men were recruited. Data were
      collected using a standardized questionnaire and by cross-checking with data from
      the cancer registry. Descriptive and comparative analyses were performed to
      evaluate persisting UI and SD at 2years. RESULTS: At two years after treatment,
      UI was persistent in 48.8%; 41.2% had used urinary protections, and 39.2% had
      used at least 1 pad/day; 55.2% reported financial difficulties for purchasing
      protective pads. In total, 22.7% did not consult a specialist for UI. SD was
      persistent in 82.8%; 30.4% did not consult a specialist for SD. SD had a negative
      impact on the sex life of patients and their partners. After adjustment for
      cancer stage, prostatectomy was significantly associated with persisting UI and
      SD at two years. CONCLUSION: Two years after treatment, rates of persisting UI
      and/or SD remain high. Treatment by prostatectomy was significantly associated
      with an increased risk of persisting adverse effects at two years. The different
      toxicities between treatments should be presented to patients before initiating
      therapy in order to encourage the patient to contributed to shared treatment
      decision-making.

PMID- 27692731
TI  - [Prevalence and management of pain in patients with metastatic cancer in Franche
      Comte].
AB  - INTRODUCTION: Pain management is a major public health problem, especially in
      oncology. In order to assess professional practice, the IRFC-FC conducted a
      survey amongst patients with metastatic osteophilic solid tumor in Franche-Comte.
      The aims were to assess the pain prevalence, and its characteristics, its
      management and its impact on patients' quality of life in patients in pain.
      METHODS: An observational, prospective and multicenter survey was conducted using
      a self-report questionnaire. Patients with metastatic breast or prostate cancer
      managed in 5 day-hospitals of the IRFC-FC over a period of three months were
      included. RESULTS: Two hundred thirty-three questionnaires were analyzed. Pain
      prevalence rate was 48.5%. Three quarters of patients in pain had chronic
      background pain, moderate to severe, with or without breakthrough pain.
      Considering their pain intensity and their analgesic therapy, 42.0% of patients
      seem to have an inadequate treatment. Eighty-five percent of treated patients
      reported to be compliant and felt that their pain was well managed despite a
      strong impact on their quality of life. CONCLUSION: The setting of a specific
      clinical pathway is essential to secure the standardized, optimal and efficient
      management of patients in pain. The assessment of patient satisfaction and
      quality of life must be integrated in clinical practice to identify patients in
      pain for which the treatment is inappropriate.

PMID- 27692732
TI  - Variation among pathologists' treatment suggestions for melanocytic lesions: A
      survey of pathologists.
AB  - BACKGROUND: The extent of variability in treatment suggestions for melanocytic
      lesions made by pathologists is unknown. OBJECTIVE: We investigated how often
      pathologists rendered suggestions, reasons for providing suggestions, and
      concordance with national guidelines. METHODS: We conducted a cross-sectional
      survey of pathologists. Data included physician characteristics, experience, and
      treatment recommendation practices. RESULTS: Of 301 pathologists, 207 (69%) from
      10 states (California, Connecticut, Hawaii, Iowa, Kentucky, Louisiana, New
      Jersey, New Mexico, Utah, and Washington) enrolled. In all, 15% and 7% reported
      never and always including suggestions, respectively. Reasons for offering
      suggestions included improved care (79%), clarification (68%), and legal
      liability (39%). Reasons for not offering suggestions included referring
      physician preference (48%), lack of clinical information (44%), and expertise
      (29%). Training and caseload were associated with offering suggestions (P < .05).
      Physician suggestions were most consistent for mild/moderate dysplastic nevi and
      melanoma. For melanoma in situ, 18 (9%) and 32 (15%) pathologists made
      suggestions that undertreated or overtreated lesions based on National
      Comprehensive Cancer Network (NCCN) guidelines, respectively. For invasive
      melanoma, 14 (7%) pathologists made treatment suggestions that undertreated
      lesions based on NCCN guidelines. LIMITATIONS: Treatment suggestions were self
      reported. CONCLUSIONS: Pathologists made recommendations ranging in consistency.
      These findings may inform efforts to reduce treatment variability and optimize
      patterns of care delivery for patients.

PMID- 27692734
TI  - Characteristics and treatment of postirradiation morphea: A retrospective
      multicenter analysis.

PMID- 27692733
TI  - Tofacitinib improves pruritus and health-related quality of life up to 52 weeks:
      Results from 2 randomized phase III trials in patients with moderate to severe
      plaque psoriasis.
AB  - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that improves clinical
      measures of psoriasis. OBJECTIVE: We sought to assess patient-reported outcomes
      in tofacitinib-treated patients with moderate to severe plaque psoriasis over 52
      weeks. METHODS: In 2 identical, phase III studies (Oral treatment for Psoriasis
      Trial Pivotal 1 [NCT01276639], n = 901, and Pivotal 2 [NCT01309737], n = 960),
      patients were randomized 2:2:1 to receive 5 or 10 mg of tofacitinib or placebo,
      twice daily. At week 16, placebo-treated patients were re-randomized to
      tofacitinib. Dermatology Life Quality Index score, Itch Severity Item score,
      Patient Global Assessment score, and patient satisfaction were assessed. RESULTS:
      Baseline Dermatology Life Quality Index score indicated substantial health
      related quality of life impairment. At week 16, a greater proportion of patients
      achieved Dermatology Life Quality Index score of 1 or less (no effect of
      psoriasis on health-related quality of life) with tofacitinib 5 and 10 mg twice
      daily versus placebo (Oral treatment for Psoriasis Trial Pivotal 1/2: 26.7%/28.6%
      and 40.2%/48.2% vs 4.6%/6.0%, respectively; P < .0001); improvements were
      maintained through week 52. Similar patterns were observed with Patient Global
      Assessment. Improvements in itch were particularly rapid, observed 1 day after
      treatment initiation for both tofacitinib doses versus placebo (P < .05). At week
      16, more patients were satisfied with tofacitinib versus placebo (P < .0001).
      LIMITATIONS: Clinical nonresponders discontinued at week 28. CONCLUSIONS:
      Tofacitinib demonstrated improvement in health-related quality of life and
      patient-reported symptoms that persisted over 52 weeks.

PMID- 27692735
TI  - Intralesional triamcinolone for flares of hidradenitis suppurativa (HS): A case
      series.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of
      the hair follicle. Standard practice of managing acute flares with corticosteroid
      injection lacks scientific evidence. OBJECTIVE: We sought to assess the outcomes
      of routine treatment using intralesional triamcinolone (triamcinolone acetonide
      10 mg/mL) in the management of acute flares in HS. METHODS: This was a
      prospective case series evaluating the effect of intralesional corticosteroids
      for alleviation of acute flares in HS. Physician- and patient-reported outcomes
      were noted. RESULTS: Significant reductions in physician-assessed erythema
      (median score from 2-1, P < .0001), edema (median score from 2-1, P < .0001),
      suppuration (median score from 2-1, P < .0001), and size (median score from 3-1,
      P < .0001) was demonstrated at follow-up. A significant difference in patient
      reported pain visual analog scale scores occurred after 1 day (from 5.5-2.3, P <
      .005) and from day 1 to day 2 (from 2.3-1.4, P < .002). LIMITATIONS: Small study
      size, open single-arm design, and short follow-up time are the limitations of
      this study. CONCLUSION: Intralesional injection of corticosteroids is perceived
      as beneficial by physicians and patients in the management of HS flares by
      reducing pain after 1 day and signs of inflammation approximately 7 days later.

PMID- 27692736
TI  - The effect of smoking and age on the response to first-line therapy of
      hidradenitis suppurativa: An institutional retrospective cohort study.
AB  - BACKGROUND: Treatment for hidradenitis suppurativa is often empiric and
      inadequate, and determining which patients will respond is difficult. OBJECTIVE:
      We sought to determine which patient factors are associated with a positive
      response to first-line medical therapy. METHODS: A single-center retrospective
      cohort study of all patients with hidradenitis suppurativa seen between January
      1, 1992, and October 1, 2014, was conducted. Response to first-line medical
      therapy (oral/topical antibiotics, intralesional corticosteroids, and topical
      washes) was examined at follow-up within 6 months of initiating therapy. A
      multivariate binary logistic regression model was built examining response to
      treatment and the interplay of patient factors and treatment initiated. RESULTS:
      In all, 198 patients were included in the final model. Nonsmokers (odds ratio
      2.634, 95% confidence interval 1.301-5.332, P = .007) and older individuals (odds
      ratio 1.046 for each additional year, 95% confidence interval 1.020-1.072, P <
      .001) were more likely to have improvement at follow-up. In addition, current
      smokers differed significantly from nonsmokers in several regards. LIMITATIONS:
      The retrospective nature of this study is a limitation, as is relying on
      classification of disease severity from physical examination findings in some
      patients. CONCLUSIONS: The results of this study suggest that clinicians may be
      able to more accurately predict which patients with hidradenitis suppurativa will
      respond to first-line medical therapy, and which patients may require therapy
      escalation.

PMID- 27692737
TI  - [Comparison of the effects of sugammadex and neostigmine on postoperative nausea
      and vomiting].
AB  - BACKGROUND AND OBJECTIVES: The aim of our study is to compare the effects of
      sugammadex and neostigmine, used for neuromuscular blockage antagonism, on
      postoperative nausea and vomiting (PONV). METHODS: Our study was completed with
      98 ASA I-II risk patients undergoing endotracheal intubation under general
      anesthesia. At the end of the surgery patients were randomly allocated into two
      groups given 2mgkg-1 sugammadex (Group S) or 50MUgkg-1 neostigmine plus 0.2mgkg-1
      atropine (Group N). Monitoring and recording times were set as 1 hour
      postoperative and from 1-6, 6-12, and 12-24hours. The anti-emetic amounts
      administered were recorded. RESULTS: In the first postoperative hour 13 patients
      in Group N (27%) and 4 in Group S (8%) were observed to have nausea and/or
      vomiting and the difference was statistically significant (p=0.0016). During the
      24hours of monitoring there was no significant difference in the incidence and
      severity of PONV (p>0.05), however the number of patients given ondansetron for
      PONV treatment in Group N was significantly higher than the number in Group S (16
      in Group N, 6 in Group S, p<0.011). CONCLUSIONS: At the end of our study
      comparing neostigmine with sugammadex for neuromuscular blockage antagonism, we
      found use of sugammadex had lower incidence of PONV in the postoperative 1st hour
      and less anti-emetic use in 24hours of monitoring.

PMID- 27692738
TI  - [The effect of intra-articular levobupivacaine on shoulder cartilage at different
      doses-experimental study].
AB  - BACKGROUND AND OBJECTIVES: In this study it was aimed to examine the histological
      and morphometric effects on cartilage structure of intra-articular application of
      levobupivacaine to the shoulder joint. METHODS: In twenty New Zealand adult male
      rabbits, 35 shoulders were used for the study and prepared in 5 groups of 7.
      These groups were defined as Groups L1, L2, L3 and L4 which were right shoulders
      administered with 0.25% and 0.5% levobupivacaine, Group C which were left
      shoulders as the control group and Groups S1 and S2 which were left shoulders
      administered with 0.9% saline. On the 2nd and 15th days the animals were killed,
      the glenohumeral joints were evaluated macroscopically then cartilage samples
      were taken. These samples were evaluated with Mankin score, and
      histomorphometrically by measuring the thickness of the cartilage between the
      superficial cartilage layer and the tidemark and the thickness of calcified
      cartilage between the tidemark and the subchondral bone. RESULTS:
      Macroscopically, on the 15th day the joint fluid was seen to have reduced in all
      the groups. After microscopic evaluation, the highest Mankin score (mean: 3.14+/
      2.1/14) was in the L4 group (15th day 0.5% levobupivacaine) and was found to be
      statistically significant (p<0.05). No statistically significant difference was
      determined between the other groups. CONCLUSIONS: Histologically, as the highest
      Mankin score was in the L4 group, this indicates that in a single intra-articular
      injection of levobupivacaine a low concentration should be selected. LEVEL OF
      EVIDENCE: Level 5, animal study.

PMID- 27692739
TI  - Challenges in reporting systematic reviews on epidemiological sport injury data:
      Letter to the editor re: "Upholding standards of reporting in the synthesis of
      dance epidemiology literature" re: "Prevalence and profile of musculoskeletal
      injuries in ballet dancers: A systematic review and meta-analysis".

PMID- 27692740
TI  - Strength training for plantar fasciitis and the intrinsic foot musculature: A
      systematic review.
AB  - The aim was to critically evaluate the literature investigating strength training
      interventions in the treatment of plantar fasciitis and improving intrinsic foot
      musculature strength. A search of PubMed, CINHAL, Web of Science, SPORTSDiscus,
      EBSCO Academic Search Complete and PEDRO using the search terms plantar
      fasciitis, strength, strengthening, resistance training, intrinsic flexor foot,
      resistance training. Seven articles met the eligibility criteria. Methodological
      quality was assessed using the modified Downs and Black checklist. All articles
      showed moderate to high quality, however external validity was low. A comparison
      of the interventions highlights significant differences in strength training
      approaches to treating plantar fasciitis and improving intrinsic strength. It was
      not possible to identify the extent to which strengthening interventions for
      intrinsic musculature may benefit symptomatic or at risk populations to plantar
      fasciitis. There is limited external validity that foot exercises, toe flexion
      against resistance and minimalist running shoes may contribute to improved
      intrinsic foot musculature function. Despite no plantar fascia thickness changes
      being observed through high-load plantar fascia resistance training there are
      indications that it may aid in a reduction of pain and improvements in function.
      Further research should use standardised outcome measures to assess intrinsic
      foot musculature strength and plantar fasciitis symptoms.

PMID- 27692742
TI  - Oral hygiene behaviours and tooth-loss assessment in patients with diabetes: A
      report from a diabetology centre in Belgium.

PMID- 27692741
TI  - Functional Imaging in Radiotherapy in the Netherlands: Availability and Impact on
      Clinical Practice.
AB  - AIMS: Functional imaging with positron emission tomography/computed tomography
      (PET/CT) and multiparametric magnetic resonance (mpMR) is increasingly applied
      for radiotherapy purposes. However, evidence and experience are still limited,
      and this may lead to clinically relevant differences in accessibility,
      interpretation and decision making. We investigated the current patterns of care
      in functional imaging for radiotherapy in the Netherlands in a care evaluation
      study. MATERIALS AND METHODS: The availability of functional imaging in
      radiotherapy centres in the Netherlands was evaluated; features available in >80%
      of academic and >80% of non-academic centres were considered standard of care.
      The impact of functional imaging on clinical decision making was evaluated using
      case questionnaires on lung, head/neck, breast and prostate cancer, with multiple
      choice questions on primary tumour delineation, nodal involvement, distant
      metastasis and incidental findings. Radiation oncologists were allowed to discuss
      cases in a multidisciplinary approach. Ordinal answers were evaluated by median
      and interquartile range (IQR) to identify the extent and variability of clinical
      impact; additional patterns were evaluated descriptively. RESULTS: Information
      was collected from 18 radiotherapy centres in the Netherlands (all except two).
      PET/CT was available for radiotherapy purposes to 94% of centres; 67% in the
      treatment position and 61% with integrated planning CT. mpMR was available to all
      centres; 61% in the treatment position. Technologists collaborated between
      departments to acquire PET/CT or mpMR for radiotherapy in 89%. All sites could
      carry out image registration for target definition. Functional imaging generally
      showed a high clinical impact (average median 4.3, scale 1-6) and good observer
      agreement (average IQR 1.1, scale 0-6). However, several issues resulted in
      ignoring functional imaging (e.g. positional discrepancies, central necrosis) or
      poor observer agreement (atelectasis, diagnostic discrepancies, conformation
      strategies). CONCLUSIONS: Access to functional imaging with PET/CT and mpMR for
      radiotherapy purposes, with collaborating technologists and multimodal
      delineation, can be considered standard of care in the Netherlands. For several
      specific clinical situations, the interpretation of images may benefit from
      further standardisation.

PMID- 27692744
TI  - Genomic organization and modulation of gene expression of the TGF-beta and FGF
      pathways in the allotetraploid frog Xenopus laevis.
AB  - Inductive interactions mediated by the TGF-beta and FGF-MAPK pathways are
      essential for specification of the germ layers and embryonic body axes during
      early vertebrate embryogenesis. TGF-beta and FGF ligands signal through receptor
      Ser/Thr and Tyr kinases, respectively, and these signaling pathways cross-talk to
      regulate transcription and cell behavior. The allotetraploid Xenopus laevis and
      its ancestral diploid Xenopus tropicalis are versatile model organisms with which
      to study the inductive interactions and mechanisms of these signal transduction
      pathways. Here we have analyzed the draft genome of X. laevis with respect to the
      genomic organization and differential expression of genes in the TGF-beta and FGF
      pathways. Genomic structure and gene expression analyses of pathway components in
      X. laevis revealed that genetic modulations, including deletions resulting in
      singletons and differential expression of homeologs, have occurred frequently
      among extracellular regulatory factors of the TGF-beta pathway after
      allotetraploidization. Moreover, differential gene expression was found for
      factors regulating various cellular responses including co-receptors, decoy
      receptors, and intracellular negative regulators in both the TGF-beta and FGF
      MAPK pathways. We summarize the patterns of genetic alterations in the
      allotetraploid frog X. laevis and discuss the importance of these changes with
      regard to developmental processes.

PMID- 27692745
TI  - Neil Poulter: upping the pressure on hypertension.

PMID- 27692746
TI  - Department of Error.

PMID- 27692747
TI  - Gaining awareness: Cultivating clinical reflection in nursing students.
AB  - Earlier this year, in an article published in Nurse Education in Practice, a
      nurse educator in our school of nursing described an activity designed to refresh
      and inspire undergraduate nursing students who feel fatigued at the end of the
      day, and/or anxious, pressured, or overwhelmed during their clinical practice
      experiences (Andersen, 2016). We are some of those students who participated in
      this activity during some of our therapeutic debriefing and reflective
      discussions and we would like to respond by describing our experiences.

PMID- 27692748
TI  - [Measurement of fractional flow reserve in patients with severe aortic stenosis:
      A valid test?]
AB  - A 54-year-old woman was hospitalized for an acute pulmonary oedema revealing a
      severe aortic stenosis (AS) associated with an aortic aneurysm and a left
      ventricular hypertrophy (LVH). The coronary angiography found an equivocal left
      main lesion. Fractional flow reserve (FFR) showed hemodynamic significance
      (FFR=0.78) and optical coherence tomography confirmed this result with a minimal
      lumen area of 4.9mm2. FFR-guided percutaneous intervention is reported to improve
      outcome in patients with stable coronary disease. However, only few data are
      available in cases of AS. In this condition, secondary LVH is associated with
      microcirculatory dysfunction, which interferes with optimal hyperemia. An
      elevated right atrial pressure could also modify FFR measurement. This risk of
      underestimation of a coronary lesion in patients with severe AS has to be taken
      into consideration in clinical practice.

PMID- 27692749
TI  - [Atypical form of cor triatrium in a 59-year-old man].
AB  - Cor triatrium is a rare congenital heart disease typically diagnosed amongst very
      young patients. Delayed diagnosis in the elderly is much more unusual. We report
      the case of a 59-year-old male with unremarkable medical history in whom we have
      discovered, on an echocardiography performed for an exploration of transient
      ischemic accident with atrial fibrillation, a particular form of an isolated cor
      triatrium dextrum investigated with multimodality imaging.

PMID- 27692750
TI  - [Prethrombus acute constitution during dobutamine stress echocardiography].
AB  - Although generally regarded as a safe stress modality, dobutamine stress
      echocardiography (DSE) has been associated with several well described
      complications. However, to our knowledge, acute constitution of thrombi during
      the stress test has never been described. In this report, we present the case of
      a 64 year-old man with a history of ischemic heart disease who underwent a
      preoperative DSE; during the test, we witnessed a striking acute constitution of
      an intense prethrombotic state with almost a formation of a highly mobile massive
      thrombus adjacent to the infero-apical segment spontaneously resolving few
      minutes after the end of the test.

PMID- 27692751
TI  - [Cardiac rehabilitation in "sports" patients].
AB  - BACKGROUND: Cardiac rehabilitation (CR) addresses for the greater part a middle
      aged sedentary population. Nevertheless, some patients referred in CR are active
      or sportive, and care for these patients is less known. AIM OF THE STUDY: To
      compare the results of CR between a little or not active population and an active
      or athletic population. PATIENTS AND METHODS: Every patient referred in a CR
      department in Loire-Atlantique between 2010 and 2016 were included either in the
      group 1 (sedentary or little active) or in the group 2 (at least once a week
      physical training).) RESULTS: Among 2916 patients included, 2288 patients did two
      exercise tests, the functional capacity in the group 1 (n=2117) increased from
      4.7+/-1.2 to 5.6+/-1.3 METs versus 6.5+/-1.7 to 7.6+/-1.8 METs in the group 2
      (n=171), the gain was similar in both groups from 19+/-13% to 18+/-14% (P=0.16).
      The 6minutes Walking Test respectively increased from 445+/-91 to 517+/-89 versus
      518+/-87 to 603+/-73 meters with a gain of 18+/-18 versus 18+/-16% (P=0.93). The
      prognosis is yet to be best in the group 2 in accordance to a best maximal
      functional capacity (P<0.01). CONCLUSION: Cardiac rehabilitation is useful in
      active or athletic patients and should be prescribed based on the current
      recommendations.

PMID- 27692752
TI  - [Optimization of the management of acute heart failure. New concept of fast
      track].
AB  - The acute heart failure generates a very important number of hospitalizations for
      a high cost. A recent reflection on optimizing its management is ongoing, based
      on the fastest management in the emergency department, with a distinction between
      which patient should remain and who returns at home, and under what conditions,
      allowing to limit the number of hospitalizations. It will require a
      reorganization of emergency department and updating of decision algorithms and
      new guidelines of care.

PMID- 27692753
TI  - Quantitative 177Lu SPECT imaging using advanced correction algorithms in non
      reference geometry.
AB  - Peptide receptor therapy with 177Lu-labelled somatostatin analogues is a
      promising tool in the management of patients with inoperable or metastasized
      neuroendocrine tumours. The aim of this work was to perform accurate activity
      quantification of 177Lu in complex anthropomorphic geometry using advanced
      correction algorithms. Acquisitions were performed on the higher 177Lu photopeak
      (208keV) using a Philips IRIX gamma camera provided with medium-energy
      collimators. System calibration was performed using a 16mL Jaszczak sphere
      surrounded by non-radioactive water. Attenuation correction was performed using
      MU-maps derived from CT data, while scatter and septal penetration corrections
      were performed using the transmission-dependent convolution-subtraction method.
      SPECT acquisitions were finally corrected for dead time and partial volume
      effects. Image analysis was performed using the commercial QSPECT software. The
      quantitative SPECT approach was validated on an anthropomorphic phantom provided
      with a home-made insert simulating a hepatic lesion. Quantitative accuracy was
      studied using three tumour-to-background activity concentration ratios (6:1, 9:1,
      14:1). For all acquisitions, the recovered total activity was within 12% of the
      calibrated activity both in the background region and in the tumour. Using a 6:1
      tumour-to-background ratio the recovered total activity was within 2% in the
      tumour and within 5% in the background. Partial volume effects, if not properly
      accounted for, can lead to significant activity underestimations in clinical
      conditions. In conclusion, accurate activity quantification of 177Lu can be
      obtained if activity measurements are performed with equipment traceable to
      primary standards, advanced correction algorithms are used and acquisitions are
      performed at the 208keV photopeak using medium-energy collimators.

PMID- 27692754
TI  - Validation of Bayesian analysis of compartmental kinetic models in medical
      imaging.
AB  - INTRODUCTION: Kinetic compartmental analysis is frequently used to compute
      physiologically relevant quantitative values from time series of images. In this
      paper, a new approach based on Bayesian analysis to obtain information about
      these parameters is presented and validated. MATERIALS AND METHODS: The closed
      form of the posterior distribution of kinetic parameters is derived with a
      hierarchical prior to model the standard deviation of normally distributed noise.
      Markov chain Monte Carlo methods are used for numerical estimation of the
      posterior distribution. Computer simulations of the kinetics of F18
      fluorodeoxyglucose (FDG) are used to demonstrate drawing statistical inferences
      about kinetic parameters and to validate the theory and implementation.
      Additionally, point estimates of kinetic parameters and covariance of those
      estimates are determined using the classical non-linear least squares approach.
      RESULTS AND DISCUSSION: Posteriors obtained using methods proposed in this work
      are accurate as no significant deviation from the expected shape of the posterior
      was found (one-sided P>0.08). It is demonstrated that the results obtained by the
      standard non-linear least-square methods fail to provide accurate estimation of
      uncertainty for the same data set (P<0.0001). CONCLUSIONS: The results of this
      work validate new methods for a computer simulations of FDG kinetics. Results
      show that in situations where the classical approach fails in accurate estimation
      of uncertainty, Bayesian estimation provides an accurate information about the
      uncertainties in the parameters. Although a particular example of FDG kinetics
      was used in the paper, the methods can be extended for different pharmaceuticals
      and imaging modalities.

PMID- 27692755
TI  - Apnea After Low-Dose Ketamine Sedation During Attempted Delayed Sequence
      Intubation.
AB  - Some patients are agitated and unable to tolerate conventional preoxygenation
      methods, including face mask oxygen or noninvasive positive-pressure ventilation.
      Sedation with ketamine for preoxygenation, also known as delayed sequence
      intubation, is a technique that can be used to achieve preoxygenation in this
      patient population. No complications of delayed sequence intubation have
      previously been reported. A 60-year-old woman presented with acute hypoxic
      respiratory failure. Despite application of high-flow oxygen (60 L/min) with a
      nonrebreather face mask, her oxygen saturation remained at 93%. She would not
      accept a noninvasive positive-pressure ventilation mask, although she remained
      alert, with vigorous respiratory effort. She received 25 mg of intravenous
      ketamine (0.31 mg/kg) to allow application of noninvasive positive-pressure
      ventilation. One minute after receiving ketamine, she developed apnea; bag-valve
      mask ventilation was initiated, and she received succinylcholine and etomidate
      and was intubated on the first attempt, without complication. She had no
      respiratory effort between the onset of apnea and pharmacologic paralysis. Apnea
      can occur in critically ill patients who receive ketamine to facilitate
      preoxygenation. Sedation remains a valuable technique to enable optimal
      preoxygenation in agitated patients; however, clinicians should not perform this
      technique lightly and should be prepared to secure the patient's airway
      immediately.

PMID- 27692756
TI  - Spatial Patterns and Neighborhood Characteristics of Overall Suicide Clusters in
      Florida From 2001 to 2010.
AB  - INTRODUCTION: Although spatial examination of mortality and morbidity is becoming
      more common in health studies, the investigation of suicide death clusters within
      the neighborhood context is underutilized. The purpose of this ecological study
      is to detect high- and low-risk clusters of suicide deaths in Florida and
      determine which neighborhood characteristics distinguish clusters from non
      clusters. METHODS: The scan statistic method was used to detect overall clusters
      of completed suicides in Florida from 2001 to 2010. Regression analysis was used
      to investigate the association of neighborhood characteristics with identified
      clusters. All data synthesis and statistical analyses were conducted in 2015.
      RESULTS: Twenty-four high-risk and 25 low-risk clusters were identified. The risk
      of suicide was up to 3.4 times higher in high-risk clusters than in areas outside
      of clusters (relative risk ranged from 1.36 to 3.44, p<=0.05). Low-risk clusters
      were associated with 30%-94% decreased risk of suicide (relative risk ranged from
      0.06 to 0.70, p<=0.05). Areas with high levels of elderly concentration and
      household singularity were more likely to be in high-risk clusters, whereas areas
      with higher economic deprivation and residential density were more likely to be
      in low-risk clusters. CONCLUSIONS: This study identified general suicide patterns
      across space in the state of Florida and described the characteristics of those
      areas.

PMID- 27692757
TI  - Life Years Gained From Smoking-Cessation Counseling After Myocardial Infarction.
AB  - INTRODUCTION: Hospitalization for acute myocardial infarction (AMI) is an
      opportune time to counsel smokers to quit. Studies have demonstrated lower short
      term mortality for counseled versus non-counseled smokers; yet, little is known
      about the long-term survival benefits of post-AMI smoking-cessation counseling
      (SCC). METHODS: Data from the Cooperative Cardiovascular Project, a prospective
      cohort study of elderly patients with AMI between 1994 and 1996 with >17 years of
      follow-up, were used to evaluate the association of SCC with short- and long-term
      mortality in smokers with AMI. Life expectancy and years of potential life gained
      were used to quantify the long-term survival benefits of SCC. Cox proportional
      hazards models with exponential extrapolation were used to estimate life
      expectancy. RESULTS: The analysis included 13,815 smokers, of whom 5,695 (41.2%)
      received SCC. Non-counseled smokers had higher crude mortality than counseled
      smokers over all 17 years of follow-up. After adjustment for patient and hospital
      characteristics, SCC was associated with a 22.6% lower 30-day mortality and a
      7.5% lower mortality over 17 years. These survival differences produced higher
      life expectancy estimates for counseled smokers than non-counseled smokers at all
      ages, which resulted in average gains in life years of 0.13 (95% CI=-0.31, 0.56)
      to 0.58 (95% CI=0.25, 0.91) years, with the largest gains observed in older
      smokers. CONCLUSIONS: SCC is associated with longer life expectancy and gains in
      life years in elderly smokers with AMI, supporting the importance of post-AMI
      counseling efforts.

PMID- 27692759
TI  - Reality or singular pipe dream?

PMID- 27692758
TI  - Thoracic endovascular aortic repair (TEVAR) in proximal (type A) aortic
      dissection: Ready for a broader application?
AB  - OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) has demonstrated
      encouraging results and is gaining increasing acceptance as a treatment option
      for aortic aneurysms and dissections. Yet, its role in managing proximal aortic
      pathologies is unknown-this is important because in proximal (Stanford type A)
      aortic dissections, 10% to 30% are not accepted for surgery and 30% to 50% are
      technically amenable for TEVAR. We describe our case series of type A aortic
      dissections treated by using TEVAR. METHODS: Between year 2009 and 2016, 12
      patients with acute, subacute, or chronic type A aortic dissection with the
      proximal entry tear located between the coronaries and brachiocephalic artery
      were treated with TEVAR at 3 centers. Various stent-graft configurations were
      used to seal the proximal entry tear in the ascending aorta under rapid pacing.
      RESULTS: A total of 12 patients (9 male, 3 female), mean age 81 +/- 7 years,
      EuroSCORE II 9.1 +/- 4.5, underwent TEVAR for the treatment of type A aortic
      dissection. Procedural success was achieved in 11 of 12 patients (91.7%). There
      was 1 minor stroke and 1 intraprocedural death. No additional deaths were
      reported at 30 days. At 36 months, there were 4 further deaths (all from
      nonaortic causes). The mean survival of these 4 deceased was 23 months (range 15
      36 months). Follow-up computed tomography demonstrated favorable aortic
      remodeling. CONCLUSIONS: TEVAR is feasible and reveals promising early results in
      selected patients with type A aortic dissection who are poor candidates for
      surgical repair. The current iteration of stent-graft technology, however, needs
      to be adapted to features specific to the ascending aorta.

PMID- 27692760
TI  - Reproducibility and replicability of science and thoracic surgery.

PMID- 27692762
TI  - Discussion.

PMID- 27692761
TI  - Percutaneous placement of large cannula into the internal jugular vein for
      minimally invasive surgery: Where do we go?

PMID- 27692763
TI  - A transapical-to-aorta double lumen cannula-based neonate left ventricular assist
      device efficiently unloads the left ventricle in neonate lambs.
AB  - OBJECTIVE: We are developing a transapical-to-aorta double lumen cannula (TAA
      DLC) for a less-invasive/more dependable neonatal left ventricular assist device.
      METHODS: The 18-Fr TAA DLC prototypes were bench tested and evaluated for 6 hours
      in neonate lambs (n = 6, 7.7-10 kg). The cardiac apex was exposed through a left
      anterolateral thoracotomy through the sixth intercostal space. The TAA DLC was
      inserted through a mattress stitch on apex, passing LV-aortic valve, into the
      ascending aorta with insertion/deployment guided by pressure waveform. The DLC
      was connected to blood pump. Cardiac output and aortic root blood flow were
      measured with perivascular flow sensors. Activated clotting time was maintained
      at 180-250 seconds. RESULTS: The DLC pumped up to 1.8 L/min flow against 63 mm Hg
      drainage pressure and 145 mm Hg infusion pressure in bench testing. In all lambs,
      the DLC was inserted/deployed properly within 1 minute on the first attempt.
      Pumping flow was maintained at 1.2-1.3 L/min. Systolic arterial pressure
      decreased and diastolic arterial pressure/mean arterial pressure increased,
      indicating decreased afterload and increased perfusion pressure. Left ventricular
      end-diastolic pressure decreased from 13 +/- 1 mm Hg to 6 +/- 2 mm Hg, indicating
      decreased preload. Aortic root backward flow was 2.4% +/- 0.6% without DLC and
      3.5% +/- 0.8% of cardiac output with DLC, indicating no significant DLC-induced
      aortic valve regurgitation. After 6 hours, free hemoglobin was <5 mg/dL with
      hemoglobin/platelets unchanged. No significant thrombus was found in pumps/DLCs.
      No trauma was found in LV, aortic valve, and aorta. CONCLUSIONS: Our TAA DLC
      based neonate left ventricular assist device efficiently unloaded the LV in
      lambs.

PMID- 27692764
TI  - Just when you thought you'd seen everything.

PMID- 27692765
TI  - Discussion.

PMID- 27692767
TI  - Discussion.

PMID- 27692766
TI  - Pulmonary flow study predicts survival in pulmonary atresia with ventricular
      septal defect and major aortopulmonary collateral arteries.
AB  - BACKGROUND: We hypothesized that mean pulmonary artery pressure (PAP) detected on
      a pulmonary flow study may predict medium-term survival and right ventricular
      systolic pressure (RVSP) in patients with pulmonary atresia (PA), ventricular
      septal defect (VSD), and major aortopulmonary collateral arteries (MAPCAs).
      METHODS: Fifty patients with PA/VSD/MAPCAs underwent unifocalization between 2000
      and 2013, and 40 of these patients had a pulmonary flow study since 2003.
      Predictability of the mean PAP on VSD status, medium-term survival,
      reintervention, and RVSP were analyzed. RESULTS: Forty-seven of the 50 patients
      (94%) had complete unifocalization at a median age of 11 months (range, 1-194
      months), and 37 patients (74%) achieved VSD closure. Among the 40 patients who
      underwent a pulmonary flow study, the VSD was closed in 34 (85%), with salvage
      VSD fenestration in 4 (10%), and was intentionally left open in 6 (15%). Survival
      was 85.5% at 1 year and 78.5% at 5 years. A mean PAP >=25 mm Hg was associated
      with worse survival (P = .011). Cox regression analysis identified a mean PAP
      >=25 mm Hg as the sole predictor for death (P = .037). Patients with an open VSD
      had an increased risk of reoperation (P = .001) and pulmonary artery
      reintervention (P = .010), and had a trend toward increased risk of death (P =
      .059), compared with those with a closed VSD. CONCLUSIONS: PAP obtained from the
      intraoperative pulmonary flow study is associated with medium-term survival and
      late RVSP in patients with PA/VSD/MAPCAs. VSD closure for patients with a mean
      PAP >=25 mm Hg on a flow study is considered high risk, and sensible judgment and
      a low threshold for VSD fenestration are required.

PMID- 27692768
TI  - Concept of an expandable cardiac valve for surgical implantation in infants and
      children.
AB  - BACKGROUND: Options for cardiac valve replacement in children are limited to
      fixed-diameter prostheses that do not accommodate for somatic growth. An
      externally stented bovine jugular vein graft has been modified for surgical valve
      replacement in pediatric patients, with the intention of subsequent valve
      expansion in the catheterization laboratory as the child grows. METHODS:
      Pediatric patients at a single institution who underwent surgical implantation of
      an expandable bovine jugular vein valve between 2010 and 2014 were reviewed
      retrospectively. Forty-two patients underwent implantation at median age of 10
      months (range, 3 weeks to 5.8 years) in aortic, mitral, pulmonary, or tricuspid
      positions. Numerous techniques for valve modification and implantation were used.
      RESULTS: The valve was competent with low gradient acutely postoperatively in all
      patients. Eight patients experienced central or paravalvular deterioration, and 7
      required reoperation for valve-related adverse outcomes. Twenty patients
      underwent at least one previous valve repair or replacement. Twenty patients
      underwent 32 episodes of catheter-based balloon expansion of the valve,
      exhibiting a significant decrease in median gradient from 12 mm Hg to 8 mm Hg (P
      < .001) with no significant increase in grade of regurgitation. At 12 months
      after implantation, Kaplan-Meier analysis indicated that 88% would be expected to
      be free from reoperation (95% confidence interval, 78%-98%). A total of 6 deaths
      occurred, 3 before discharge and 3 late. CONCLUSIONS: A surgically implanted
      externally reinforced bovine jugular vein demonstrates acceptable short-term
      function and is amenable to catheter-based enlargement as the child grows.
      Modification of valve design and implantation techniques are necessary to reduce
      perivalvular complications.

PMID- 27692769
TI  - Synthesis and antimicrobial activity of small cationic amphipathic aminobenzamide
      marine natural product mimics and evaluation of relevance against clinical
      isolates including ESBL-CARBA producing multi-resistant bacteria.
AB  - A library of small aminobenzamide derivatives was synthesised to explore a
      cationic amphipathic motif found in marine natural antimicrobials. The most
      potent compound E23 displayed minimal inhibitory concentrations (MICs) of 0.5
      2MUg/ml against several Gram-positive bacterial strains, including methicillin
      resistant Staphylococcus epidermidis (MRSE).E23 was also potent against 275
      clinical isolates including Staphylococcus aureus, Enterococcus spp., Escherichia
      coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as methicillin
      resistant S. aureus (MRSA), vancomycin-resistant enterococci (VRE), and ESBL
      CARBA producing multi-resistant Gram-negative bacteria. The study demonstrates
      how structural motifs found in marine natural antimicrobials can be a valuable
      source for making novel antimicrobial lead-compounds.

PMID- 27692770
TI  - Effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of
      Streptococcus pneumoniae and Haemophilus influenzae among children in Sao Paulo,
      Brazil.
AB  - In March 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine
      (PCV10) in the routine infant immunization program using a 4-dose schedule and
      catch-up for children <23months. We investigated PCV10 effect on nasopharyngeal
      carriage with vaccine-type Streptococcus pneumoniae (Spn) and non-typeable
      Haemophilus influenzae (NTHi) among children in Sao Paulo city. Cross-sectional
      surveys were conducted in 2010 (baseline) and 2013 (post-PCV10). Healthy PCV
      naive children aged 12-23months were recruited from primary health centers during
      immunization campaigns. Nasopharyngeal swabs were collected and tested for Hi;
      for Spn, all baseline and a stratified random sample of 400 post-PCV10 swabs were
      tested. We compared vaccine-type Spn and NTHi carriage prevalence pre-/post
      PCV10, and used logistic regression to estimate PCV10 effectiveness (1-adjusted
      odds ratio*100%). Overall 501 children were included in the baseline and 1167 in
      the post-PCV10 survey (including 400 tested for Spn). Spn was detected in 40.3%
      of children at baseline and 48.8% post-PCV10; PCV10 serotypes were found in 19.8%
      and 1.8% respectively, representing a decline of 90.9% (p<0.0001). Carriage of
      vaccine-related serotypes increased (10.8-21.0%, p<0.0001), driven primarily by a
      rise in serotype 6C (1.8-11.2%, p<0.0001); carriage of serotypes 6A and 19A did
      not significantly change. PCV10 effectiveness (4 doses) against vaccine-type
      carriage was 97.3% (95% confidence interval 88.7-99.3). NTHi prevalence increased
      from 26.0% (130/501) to 43.6% (509/1167, p<0.0001); PCV10 vaccination seemed
      significantly associated with NTHi carriage, even after adjusting for other known
      risk factors. Carriage with PCV10 serotypes among toddlers declined dramatically
      following PCV10 introduction in Sao Paulo, Brazil. No protection of PCV10 against
      NTHi was observed. Our findings contribute to a growing body of evidence of PCV10
      impact on vaccine-type carriage and highlight the importance of PCV10 as a tool
      to reduce the burden of pneumococcal disease in Brazil and globally.

PMID- 27692771
TI  - Identification of Plasmodium falciparum reticulocyte binding protein homologue 5
      interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine
      candidate.
AB  - Genetic variability in Plasmodium falciparum malaria parasites hampers current
      malaria vaccine development efforts. Here, we hypothesize that to address the
      impact of genetic variability on vaccine efficacy in clinical trials, conserved
      antigen targets should be selected to achieve robust host immunity across
      multiple falciparum strains. Therefore, suitable vaccine antigens should be
      assessed for levels of polymorphism and genetic diversity. Using a total of one
      hundred and two clinical isolates from a region of high malaria transmission in
      Uganda, we analyzed extent of polymorphism and genetic diversity in four recently
      reported novel blood-stage malaria vaccine candidate proteins: Rh5 interacting
      protein (PfRipr), GPI anchored micronemal antigen (PfGAMA), rhoptry-associated
      leucine zipper-like protein 1 (PfRALP1) and Duffy binding-like merozoite surface
      protein 1 (PfMSPDBL1). In addition, utilizing the wheat germ cell-free system, we
      expressed recombinant proteins for the four candidates based on P. falciparum
      laboratory strain 3D7 sequences, immunized rabbits to obtain specific antibodies
      (Abs) and performed functional growth inhibition assay (GIA). The GIA activity of
      the raised Abs was demonstrated using both homologous 3D7 and heterologous FVO
      strains in vitro. Both pfripr and pfralp1 are less polymorphic but the latter is
      comparatively more diverse, with varied number of regions having insertions and
      deletions, asparagine and 6-mer repeats in the coding sequences. Pfgama and
      pfmspdbl1 are polymorphic and genetically diverse among the isolates with
      antibodies against the 3D7-based recombinant PfGAMA and PfMSPDBL1 inhibiting
      merozoite invasion only in the 3D7 but not FVO strain. Moreover, although Abs
      against the 3D7-based recombinant PfRipr and PfRALP1 proteins potently inhibited
      merozoite invasion of both 3D7 and FVO, the GIA activity of anti-PfRipr was much
      higher than that of anti-PfRALP1. Thus, PfRipr is regarded as a promising blood
      stage vaccine candidate for next-generation vaccines against P. falciparum.

PMID- 27692772
TI  - Assessing strategies for increasing urban routine immunization coverage of
      childhood vaccines in low and middle-income countries: A systematic review of
      peer-reviewed literature.
AB  - INTRODUCTION: Immunization programs in developing countries increasingly face
      challenges to ensure equitable delivery of services within cities where rapid
      urban growth can result in informal settlements, poor living conditions, and
      heterogeneous populations. A number of strategies have been utilized in
      developing countries to ensure high community demand and equitable availability
      of urban immunization services; however, a synthesis of the literature on these
      strategies has not previously been undertaken. METHODS: We reviewed articles
      published in English in peer-reviewed journals between 1990 and 2013 that
      assessed interventions for improving routine immunization coverage in urban areas
      in low- and middle-income countries. We categorized the intervention in each
      study into one of three groups: (1) interventions aiming to increase utilization
      of immunization services; (2) interventions aiming to improve availability of
      immunization services by healthcare providers, or (3) combined availability and
      utilization interventions. We summarized the main quantitative outcomes from each
      study and effective practices from each intervention category. RESULTS: Fifteen
      studies were identified; 87% from the African, Eastern Mediterranean and
      Southeast Asian regions of the World Health Organization (WHO). Six studies were
      randomized controlled trials, eight were pre- and post-intervention evaluations,
      and one was a cross-sectional study. Four described interventions designed to
      improve availability of routine immunization services, six studies described
      interventions that aimed to increase utilization, and five studies aiming to
      improve both availability and utilization of services. All studies reported
      positive change in their primary outcome indicator, although seven different
      primary outcomes indicators were used across studies. Studies varied considerably
      with respect to the type of intervention assessed, study design, and length of
      intervention assessment. CONCLUSION: Few studies have assessed interventions
      designed explicitly for the unique challenges facing immunization programs in
      urban areas. Further research on sustainability, scalability, and cost
      effectiveness of interventions is needed to fill this gap.

PMID- 27692774
TI  - Can Sentinel Lymph Node Biopsy Be Spared in Papillary Carcinoma of the Breast?
AB  - BACKGROUND: Papillary carcinoma (PC) of the breast represents ~0.5% of all newly
      diagnosed cases of breast cancer and usually has an indolent course. The current
      data suggest lack of a consensus in the surgical management of this disease.
      Because patients can occasionally develop metastatic disease, sentinel lymph node
      (SLN) biopsy is often performed during surgery. MATERIALS AND METHODS: In the
      present study, we retrospectively evaluated the histologic characteristics of 99
      cases of PC with or without associated frank invasive carcinoma, including 43
      encapsulated or intracystic PCs, 24 solid PCs, and 32 intraductal PCs, and
      correlated these with the incidence of nodal metastasis. RESULTS: Of the 99
      cases, 64 were tumor stage Tis (noninvasive), 5 were T1 microinvasive, 17 T1a, 5
      T1b, 5 T1c, and 3 were T2. A total of 37 patients (37%) underwent axillary
      staging, including 31 SLN biopsies and 6 axillary dissections. Only 1 patient
      (2.7%) with noninvasive solid PC had evidence of nodal metastasis. Follow-up
      information was available for 81 patients, with a mean follow-up period of 4.9
      years (range, 1-13 years). Two local recurrences, no distant metastases, and no
      disease-related deaths were recorded. CONCLUSION: PC rarely involves the lymph
      nodes even in tumors with an associated frank invasive component, and the overall
      prognosis and long-term survival is excellent. We propose that evaluation of the
      SLN should not be routinely indicated for patients with PC treated by local
      control lumpectomy.

PMID- 27692773
TI  - Brain Metastasis Prediction by Transcriptomic Profiling in Triple-Negative Breast
      Cancer.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) lacks expression of steroid
      hormone receptors (estrogen receptor alpha and progesterone) and epidermal growth
      factor receptor type 2. This phenotype shows high metastatic potential, with
      particular predilection to lungs and brain. Determination of TNBC transcriptomic
      profiles associated with high risk of brain metastasis (BM) might identify
      patients requiring alternative, more aggressive, or specific preventive and
      therapeutic approaches. PATIENTS AND METHODS: Using a cDNA-mediated annealing,
      selection, extension, and ligation assay, we investigated expression of 29,369
      gene transcripts in primary TNBC tumor samples from 119 patients-71 in discovery
      cohort A and 48 in independent cohort B-that included best discriminating genes.
      Expression of mRNA was correlated with the occurrence of symptomatic BM. RESULTS:
      In cohort A, the difference at the noncorrected P < .005 was found for 64
      transcripts (P = .23 for global test), but none showed significant difference at
      a preset level of false-discovery rate of < 10%. Of the 30 transcripts with the
      largest differences between patients with and without BM in cohort A, none was
      significantly associated with BM in cohort B. CONCLUSION: Analysis based on the
      primary tumor gene transcripts alone is unlikely to predict BM development in
      advanced TNBC. Despite its negative findings, the study adds to the knowledge on
      the biology of TNBC and paves the way for future projects using more advanced
      molecular assays.

PMID- 27692775
TI  - Rift Valley fever: still an emerging infection after 3500 years.

PMID- 27692776
TI  - Association of Rift Valley fever virus infection with miscarriage in Sudanese
      women: a cross-sectional study.
AB  - BACKGROUND: Rift Valley fever virus is an emerging mosquito-borne virus that
      causes infections in animals and human beings in Africa and the Arabian
      Peninsula. Outbreaks of Rift Valley fever lead to mass abortions in livestock,
      but such abortions have not been identified in human beings. Our aim was to
      investigate the cause of miscarriages in febrile pregnant women in an area
      endemic for Rift Valley fever. METHODS: Pregnant women with fever of unknown
      origin who attended the governmental hospital of Port Sudan, Sudan, between June
      30, 2011, and Nov 17, 2012, were sampled at admission and included in this cross
      sectional study. Medical records were retrieved and haematological tests were
      done on patient samples. Presence of viral RNA as well as antibodies against a
      variety of viruses were analysed. Any association of viral infections, symptoms,
      and laboratory parameters to pregnancy outcome was investigated using Pearson's
      chi2 test. FINDINGS: Of 130 pregnant women with febrile disease, 28 were infected
      with Rift Valley fever virus and 31 with chikungunya virus, with typical clinical
      and laboratory findings for the infection in question. 15 (54%) of 28 women with
      an acute Rift Valley fever virus infection had miscarriages compared with 12
      (12%) of 102 women negative for Rift Valley fever virus (p<0.0001). In a multiple
      logistic regression analysis, adjusting for age, haemorrhagic disease, and
      chikungunya virus infection, an acute Rift Valley fever virus infection was an
      independent predictor of having a miscarriage (odds ratio 7.4, 95% CI 2.7-20.1;
      p<0.0001). INTERPRETATION: This study is the first to show an association between
      infection with Rift Valley fever virus and miscarriage in pregnant women. Further
      studies are warranted to investigate the possible mechanisms. Our findings have
      implications for implementation of preventive measures, and evidence-based
      information to the public in endemic countries should be strongly recommended
      during Rift Valley fever outbreaks. FUNDING: Schlumberger Faculty for the Future,
      CRDF Global (31141), the Swedish International Development Cooperation Agency,
      the County Council of Vasterbotten, and the Faculty of Medicine, Umea University.

PMID- 27692777
TI  - 2016: the beginning of the end of rabies?

PMID- 27692778
TI  - Definition and classification of chyle leak after pancreatic operation: A
      consensus statement by the International Study Group on Pancreatic Surgery.
AB  - BACKGROUND: Recent literature suggests that chyle leak may complicate up to 10%
      of pancreatic resections. Treatment depends on its severity, which may include
      chylous ascites. No international consensus definition or grading system of chyle
      leak currently is available. METHODS: The International Study Group on Pancreatic
      Surgery, an international panel of pancreatic surgeons working in well-known,
      high-volume centers, reviewed the literature and worked together to establish a
      consensus on the definition and classification of chyle leak after pancreatic
      operation. RESULTS: Chyle leak was defined as output of milky-colored fluid from
      a drain, drain site, or wound on or after postoperative day 3, with a
      triglyceride content >=110 mg/dL (>=1.2 mmol/L). Three different grades of
      severity were defined according to the management needed: grade A, no specific
      intervention other than oral dietary restrictions; grade B, prolongation of
      hospital stay, nasoenteral nutrition with dietary restriction, total parenteral
      nutrition, octreotide, maintenance of surgical drains, or placement of new
      percutaneous drains; and grade C, need for other more invasive in-hospital
      treatment, intensive care unit admission, or mortality. CONCLUSION: This
      classification and grading system for chyle leak after pancreatic resection
      allows for comparison of outcomes between series. As with the other the
      International Study Group on Pancreatic Surgery consensus statements, this
      classification should facilitate communication and evaluation of different
      approaches to the prevention and treatment of this complication.

PMID- 27692779
TI  - Incidence and characteristics of chemical burns.
AB  - OBJECTIVES: Chemical burns can lead to serious health outcomes. Previous studies
      about chemical burns have been performed based on burn center data so these
      studies have provided limited information about the incidence of chemical burns
      at the national level. The aim of this study was to evaluate the incidence and
      characteristics of chemical burns using nationwide databases. METHODS: A cohort
      representing the Korean population, which was established using a national health
      insurance database, and a nationwide workers' compensation database were used to
      evaluate the incidence and characteristics of chemical burns. Characteristics of
      the affected body region, depth of burns, industry, task, and causative agents
      were analyzed from two databases. The incidence of chemical burns was calculated
      according to employment status. RESULTS: The most common regions involving
      chemical burns with hospital visits were the skin followed by the eyes. For skin
      lesions, the hands and wrists were the most commonly affected regions. Second
      degree burns were the most common in terms of depth of skin lesions. The hospital
      visit incidence was 1.96 per 10,000 person-year in the general population. The
      compensated chemical burns incidence was 0.17 per 10,000 person-year. Employees
      and the self-employed showed a significantly increased risk of chemical burns
      undergoing hospital visits compared to their dependents. CONCLUSION: Chemical
      burns on the skin and eyes are almost equally prevalent. The working environment
      was associated with increased risk of chemical burns. Our results may aid in
      estimating the size of the problem and prioritizing prevention of chemical burns.

PMID- 27692780
TI  - Upon admission coagulation and platelet function in patients with thermal and
      electrical injuries.
AB  - RATIONAL: There has been increased focus on hemostatic potential and function in
      the initial assessment of the patient with traumatic injuries, that not been
      extensively studied in patients with burns. We proposed to determine the
      hemostatic potential of patients with burns upon admission to the emergency
      department and contrasted their condition with that of healthy controls and
      patients with other traumatic injuries. In addition we assessed differences due
      to thermal versus electrical injury and evaluated the effect of burn size.
      METHODS: This is a patient based prospective observational study conducted with
      delayed consented. Subjects at the highest level of trauma activation upon
      admission to the ED had a blood sample collected for research purposes and were
      subsequently consented. Hemostatic potential was measured by rapid
      thromelastography (r-TEG(r)), thrombin generation by calibrated automated
      thrombogram (CAT) and platelet function by Multiplate(r) using five activators.
      Burn subjects were compared to subjects with other traumatic injuries and
      controls. Within the burn subjects additional analysis compared mechanism
      (thermal vs. electrical) and burn size. Values are medians (IQR). RESULTS: Two
      hundred and eighty two trauma patients (with burns n=40, 14%) and 27 controls
      were enrolled. Upon admission, compared to controls, subjects with burns or
      trauma were hyper-coagulable based on r-TEG and CAT, with increased rates of clot
      formation and thrombin generation. There were no differences in burns compared to
      other traumatic injuries. The presence of hyper-coagulation did not appear to be
      related to the type of burn or the percentage of total body surface area
      involved. Employing previous defined cut points for R-TEG driven therapeutic
      interventions burn patients had similar rates of hyper- and hypo-coagulation
      noted in patients with traumatic injuries. CONCLUSION: Upon admission patients
      with burns are in a hyper-coagulable state similar to that of other trauma
      patients. Employing demonstrated cut points of hemostatic potential in trauma
      patients associated with increased risk of poor outcomes demonstrated the
      incidence in burn patients to be similar, suggesting that these values could be
      used in the early assessment of the patient with burns to guide treatment
      interventions.

PMID- 27692781
TI  - Long-term outcome of patients with very small coronary artery disease: A
      comparison of drug-eluting and bare metal stents.
AB  - BACKGROUND: Among patients with very small vessel disease and chronic kidney
      disease (CKD), the comparative efficacy of bare metal stents (BMSs) versus drug
      eluting stents (DESs) is not frequently addressed. This study aimed to evaluate
      the long-term outcomes of patients with very small vessel disease managed with
      percutaneous coronary intervention. METHODS: Our study included 158 consecutive
      patients undergoing percutaneous coronary intervention from January 2003 to
      December 2013. The primary end points were cardiovascular death and target vessel
      failure, which consisted of cardiovascular death, target vessel-related
      myocardial infarction, and ischemia-driven target vessel revascularization.
      RESULTS: BMSs were used in 37 patients, while DESs were utilized in 121 patients.
      During the mean follow-up period of 2.7 +/- 2.2 years (median 2.1 years;
      interquartile range, 1.3-4.2 years), the target vessel failure rate was 48.6%
      versus 28.1% (BMS vs. DES, p = 0.020) and the cardiovascular death rate was 27%
      versus 18.2% (BMS vs. DES, p = 0.241). The use of a DES (hazard ratio: 0.44, 95%
      confidence interval: 0.24-0.79, p = 0.006) remained the most significant
      predictor of target vessel failure after multivariate analysis. In CKD subgroup
      analysis, the benefit of a 2.25 mm DES was evident only in the subgroup with CKD,
      but such a benefit disappeared in those without CKD. CONCLUSION: Compared with
      BMSs, implantation of DESs in a patient population with very small vessel disease
      effectively reduced target vessel failure. However, the beneficial effects of
      DESs appeared to be evident only in the subgroup with CKD.

PMID- 27692782
TI  - Preoperative Anxiety and Depression Correlate With Dissatisfaction After Total
      Knee Arthroplasty: A Prospective Longitudinal Cohort Study of 186 Patients, With
      4-Year Follow-Up.
AB  - BACKGROUND: After more than 4 decades experience of total knee arthroplasty
      (TKA), there is still a group of patients who are not satisfied with the outcome.
      In spite of the improvement of many aspects around the procedure, for
      unexplainable reasons, patient dissatisfaction is still approximately the same.
      We conducted this study to analyze correlations between preoperative
      psychological aspects and dissatisfaction after TKA. METHODS: A total of 186
      patients were operated with a primary TKA. Patients filled out the Hospital
      Anxiety and Depression Scale, Visual Analog Pain Scale (0-100), and Knee injury
      and Osteoarthritis Outcome Score preoperatively and 4 years postoperatively. Four
      years postoperatively, the patients also scored their satisfaction degree with
      the outcome of the surgery. RESULTS: Of 186 patients, 27 (15%) reported that they
      were dissatisfied or uncertain with the result of their TKA 4 years
      postoperatively. Sixteen of those 27 patients had reported anxiety/depression
      preoperatively compared with 11 of 159 (7%) in the satisfied or very satisfied
      groups. Patients with preoperative anxiety or depression had more than 6 times
      higher risk to be dissatisfied compared with patients with no anxiety or
      depression (P < .001). Patients with deep prosthetic infection had 3 times higher
      risk to be dissatisfied with the operation outcome (P = .03). Dissatisfied
      patients had 1-day longer hospital stay compared with the satisfied group (P <
      .001). CONCLUSION: Preoperative anxiety and/or depression is an import predictor
      for dissatisfaction after TKA. Psychological assessment and treatment
      preoperatively might improve degree of satisfaction.

PMID- 27692783
TI  - The Role of Patient Characteristics on the Choice of Unicompartmental versus
      Total Knee Arthroplasty in Patients With Medial Osteoarthritis.
AB  - BACKGROUND: Medial unicompartmental knee arthroplasty (UKA) and total knee
      arthroplasty (TKA) are both viable treatment options for medial osteoarthritis
      (OA). However, it remains unclear when to choose for which arthroplasty
      treatment. Goals of this study were therefore to (1) compare outcomes after both
      treatments and (2) assess which treatment has superior outcomes in different
      patient subgroups. METHODS: In this retrospective cohort study, 166 patients
      received the RESTORIS MCK Medial UKA and 63 patients the Vanguard TKA and were
      radiographically matched on isolated medial OA. Western Ontario and McMaster
      Universities Arthritis Index scores were collected preoperatively and
      postoperatively (mean: 3.0 years, range: 2.0-5.0 years). RESULTS: Preoperatively,
      no differences were observed, but medial UKA patients reported better functional
      outcomes than TKA (89.7 +/- 13.6 vs 81.2 +/- 18.0, P = .001) at follow-up.Better
      functional outcomes were noted after medial UKA in patients younger than age 70
      years (89.5 +/- 14.2 vs 78.6 +/- 20.0, P = .001), with body mass index below 30
      (90.3 +/- 11.4 vs 83.6 +/- 14.9, P = .005), with body mass index above 30 (88.3
      +/- 17.5 vs 78.8 +/- 21.0, P = .034) and in females (90.6 +/- 11.0 vs 78.1 +/-
      19.4, P = .001) when compared with TKA. No differences were found in males and
      older patients between both arthroplasties. CONCLUSION: Superior functional
      outcomes were noted after medial UKA over TKA in patients presenting with medial
      OA with these prostheses. Subgroup analyses suggest that medial UKA is the
      preferred treatment in younger patients and females while no differences were
      noted in older patients and males after medial UKA and TKA. This might help the
      orthopedic surgeon in individualizing arthroplasty treatment for patients with
      medial OA.

PMID- 27692784
TI  - Tibial Tubercle Osteotomy in Revision Knee Arthroplasty.
AB  - BACKGROUND: Obtaining adequate exposure while maintaining the integrity of the
      extensor mechanism is crucial to the success of revision knee arthroplasty. This
      is particularly important in infected cases where staged procedures are
      necessary. While the use of a long, tibial tubercle osteotomy (TTO) is an
      established method to improve exposure, controversy still exists concerning
      complication rates and sequential use. METHODS: Forty-two TTOs were performed in
      revision knee arthroplasties between 2009 and 2015. Follow-up period ranged from
      3 to 24 months. Twenty-four TTOs were performed for single-stage revisions, and
      18 TTOs were performed for 2-stage infected revisions. In infected cases, the
      initial osteotomy was left unfixed between stages. Screws were used to fix the
      osteotomy flap in all cases. RESULTS: All osteotomies united with no fractures,
      and there were no extensor lags. Minor proximal migration was noted in 1 case,
      and refixation was required in another. Greater range of motion (ROM) and
      improved Oxford Knee Scores were achieved in the single-stage revision group. In
      the infected 2-stage group, sequential use did not decrease union rates, and
      infection was eradicated in 14 of the 16 knees (88%). CONCLUSION: We conclude
      that TTO is a safe and reproducible procedure when exposure needs improving in
      revision knee arthroplasty. In 2-stage revisions, sequential osteotomies do not
      decrease union rates, and leaving the osteotomy unfixed after the first stage
      does not cause any adverse issues.

PMID- 27692785
TI  - Reduced health care-associated infections in an acute care community hospital
      using a combination of self-disinfecting copper-impregnated composite hard
      surfaces and linens.
AB  - BACKGROUND: The purpose of this study was to determine the effectiveness of
      copper-impregnated composite hard surfaces and linens in an acute care hospital
      to reduce health care-associated infections (HAIs). METHODS: We performed a
      quasiexperimental study with a control group, assessing development of HAIs due
      to multidrug resistant organisms (MDROs) and Clostridium difficile in the acute
      care units of a community hospital following the replacement of a 1970s-era
      clinical wing with a new wing outfitted with copper-impregnated composite hard
      surfaces and linens. RESULTS: The study was conducted over a 25.5-month time
      period that included a 3.5-month washout period. HAI rates obtained from the
      copper-containing new hospital wing (14,479 patient-days; 72 beds) and the
      unmodified hospital wing (19,177 patient-days) were compared with those from the
      baseline period (46,391 patient-days). The new wing had 78% (P = .023) fewer HAIs
      due to MDROs or C difficile, 83% (P = .048) fewer cases of C difficile infection,
      and 68% (P = .252) fewer infections due to MDROs relative to the baseline period.
      No changes in rates of HAI were observed in the unmodified hospital wing.
      CONCLUSIONS: Copper-impregnated composite hard surfaces and linens may be useful
      technologies to prevent HAIs in acute care hospital settings. Additional studies
      are needed to determine whether reduced HAIs can be attributed to the use of
      copper-containing antimicrobial hard and soft surfaces.

PMID- 27692786
TI  - Rates of catheter-associated urinary tract infection in tertiary care hospitals
      in 3 Arabian Gulf countries: A 6-year surveillance study.
AB  - BACKGROUND: The true burden of catheter-associated urinary tract infections
      (CAUTIs) remains largely unknown because of a lack of national and regional
      surveillance reports in Gulf Cooperation Council (GCC) countries. The purpose of
      this study was to estimate location-specific CAUTI rates in the GCC region and to
      compare them with published reports from the U.S. National Healthcare Safety
      Network (NHSN) and the International Nosocomial Infection Control Consortium
      (INICC). METHODS: CAUTI rates and urinary catheter utilization between 2008 and
      2013 were calculated using NHSN methodology pooled from 6 hospitals in 3 GCC
      countries: Saudi Arabia, Oman, and Bahrain. The standardized infection ratios of
      the CAUTIs were compared with published reports of the NHSN and INICC. RESULTS: A
      total of 286 CAUTI events were diagnosed during 6 years of surveillance, covering
      89,254 catheter days and 113,807 patient days. The overall CAUTI rate was 3.2 per
      1,000 catheter days (95% confidence interval, 2.8-3.6), with an overall urinary
      catheter utilization of 0.78. The CAUTI rates showed a wide variability between
      participating hospitals, with approximately 80% reduction during the study. The
      overall compliance with the urinary catheter bundle implementation during the
      second half of the study was 65%. The risk of CAUTI in GCC hospitals was 35%
      higher than the NHSN hospitals, but 37% lower than the INICC hospitals.
      CONCLUSIONS: CAUTI rates pooled from a sample of GCC hospitals are quite
      different from rates in both developing and developed countries.

PMID- 27692788
TI  - Implementation of respiratory protection measures: Visitors of residential care
      homes for the elderly.
AB  - To evaluate the implementation of respiratory protection measures for and by
      visitors of residential care homes for the elderly in Hong Kong, a territory-wide
      cross-sectional survey was conducted. A total of 87 infection control officers,
      1,763 health care workers, and 520 visitors from 87 homes completed the
      questionnaires. Rules on respiratory protection for visitors were found to vary
      across residential care homes for the elderly. Uncooperative visitors and
      inadequate resources were identified as major barriers in the implementation of
      such measures for visitors.

PMID- 27692787
TI  - Copper alloy surfaces sustain terminal cleaning levels in a rural hospital.
AB  - OBJECTIVE: To assess the ability of copper alloy surfaces to mitigate the
      bacterial burden associated with commonly touched surfaces in conjunction with
      daily and terminal cleaning in rural hospital settings. DESIGN: A prospective
      intention-to-treat trial design was used to evaluate the effectiveness of cooper
      alloy surfaces and respective controls to augment infection control practices
      under pragmatic conditions. SETTING: Half of the patient rooms in the medical
      surgical suite in a 49-bed rural hospital were outfitted with copper alloy
      materials. The control rooms maintained traditional plastic, metal, and porcelain
      surfaces. METHODS: The primary outcome was a comparison of the bacterial burden
      harbored by 20 surfaces and components associated with control and intervention
      areas for 12 months. Locations were swabbed regardless of the occupancy status of
      the patient room. Significance was assessed using nonparametric methods employing
      the Mann-Whitney U test with significance assessed at P < .05. RESULTS:
      Components fabricated using copper alloys were found to have significantly lower
      concentrations of bacteria, at or below levels prescribed, upon completion of
      terminal cleaning. Vacant rooms were found to harbor significant concentrations
      of bacteria, whereas those fabricated from copper alloys were found to be at or
      below those concentrations prescribed subsequent to terminal cleaning.
      CONCLUSIONS: Copper alloys can significantly decrease the burden harbored on high
      touch surfaces, and thus warrant inclusion in an integrated infection control
      strategy for rural hospitals.

PMID- 27692789
TI  - Constant load and constant volume response of municipal solid waste in simple
      shear.
AB  - Constant load and constant volume simple shear testing was conducted on
      relatively fresh municipal solid waste (MSW) from two landfills in the United
      States, one in Michigan and a second in Texas, at respective natural moisture
      content below field capacity. The results were assessed in terms of two failure
      strain criteria, at 10% and 30% shear strain, and two interpretations of
      effective friction angle. Overall, friction angle obtained assuming that the
      failure plane is horizontal and at 10% shear strain resulted in a conservative
      estimation of shear strength of MSW. Comparisons between constant volume and
      constant load simple shear testing results indicated significant differences in
      the shear response of MSW with the shear resistance in constant volume being
      lower than the shear resistance in constant load. The majority of specimens were
      nearly uncompacted during specimen preparation to reproduce the state of MSW in
      bioreactor landfills or in uncontrolled waste dumps. The specimens had identical
      percentage of <20mm material but the type of <20mm material was different. The
      <20mm fraction from Texas was finer and of high plasticity. MSW from Texas was
      overall weaker in both constant load and constant volume conditions compared to
      Michigan waste. The results of these tests suggest the possibility of
      significantly lower shear strength of MSW in bioreactor landfills where waste is
      placed with low compaction effort and constant volume, i.e., "undrained",
      conditions may occur. Compacted MSW specimens resulted in shear strength
      parameters that are higher than uncompacted specimens and closer to values
      reported in the literature. However, the normalized undrained shear strength in
      simple shear for uncompacted and compacted MSW was still higher than the
      normalized undrained shear strength reported in the literature for clayey and
      silty soils.

PMID- 27692790
TI  - Changes in the ecological properties of organic wastes during their biological
      treatment.
AB  - Organic wastes, such as the organic fractions of municipal solid waste (OFMSW) or
      sewage sludge (SS), have become a serious environmental problem in Russia as well
      as in other countries. The use of these wastes as soil amendments allows their
      negative impact on the environment to be minimized. However, before these wastes
      can be used, they need to be treated appropriately in order to decrease their
      level of hazard. In this study, composting of raw SS, OFMSW, a mixture of these
      two wastes (OFMSW+SS) at a ratio 1:2 as well as the anaerobically digested
      variants of these wastes (SSd, OFMSWd and OFMSWd+SSd) mixed with oiled sawdust
      was performed. Composting was conducted in the containers containing 20kg of the
      wastes. The results of three elutriate bioassays (with water flea Daphnia magna,
      infusoria Paramecium caudatum and radish plant, Raphanus sativus) and one contact
      bioassay (with oat plant Avena sativa) were used to indirectly estimate changes
      in the hazardous properties of the biological treatments. Besides, Corg, Ntot
      content and pH were analyzed in the process of composting. Within the study
      stability tests to determine maturation process completion were not carried out.
      It was revealed, that in the process of anaerobic pretreatment for 15days, the
      toxicity increased by a mean of 1.3-, 1.9- and 1.1-fold for OFMSW, SS and
      OFMSW+SS, respectively. During composting, the toxicity level of these pretreated
      samples decreased more rapidly as compared with those which were not pretreated.
      As a result, the toxicity levels of the elutriates from the final composts made
      of pretreated wastes OFMSW, SS and OFMSW+SS were three-, two- and 17-fold lower
      for D. magna and 15-, 21- and 12-fold lower for P. caudatum. As follows from
      phytotoxicity estimations, composts from digested substrates became mature on the
      60th day and had a stimulation effect on the plants after the 90th day of
      incubation. For the composts prepared from raw substrates, a significantly longer
      period was needed for maturation. On the basis of ecotoxicity changes of the
      wastes treated, it can be concluded that anaerobic pretreatment of the municipal
      solid wastes is an effective acceleration tool for further composting and that
      waste mixtures can be treated more efficient as compared with raw wastes.

PMID- 27692791
TI  - Is there a relationship between impaired median nerve excursion and carpal tunnel
      syndrome? A systematic review.
AB  - STUDY DESIGN: Systematic review. INTRODUCTION: It is accepted that the etiology
      of carpal tunnel syndrome (CTS) is multifactorial. One of the most commonly
      accepted etiologic factors for CTS is compromise of the kinematic behavior and
      excursion of the median nerve. PURPOSE OF THE STUDY: The objective of this
      systematic review was to establish if there is a relationship between impaired
      median nerve excursion and CTS. METHODS: A systematic review, following the
      Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines,
      was conducted. Studies were sought where in vivo median nerve excursion was
      compared between people with CTS to an appropriate control group. Quality
      appraisal for each study was conducted using the Newcastle-Ottawa Scale by 2
      independent evaluators. RESULTS: Ten case-control studies using ultrasound
      imaging to quantify median nerve excursion were included. All studies were rated
      as of "moderate" methodologic quality having scored 6 or 7 (of 9 stars) for the
      Newcastle-Ottawa Scale. Seven of the 10 studies concluded that median nerve
      excursion was reduced in a CTS population when compared with controls.
      CONCLUSION: The literature suggests that median nerve excursion is reduced in
      people with CTS when compared with healthy controls. LEVEL OF EVIDENCE: 3a.

PMID- 27692793
TI  - Predicting odds of prolonged operative times.

PMID- 27692792
TI  - Incidence, characteristics, and management of recently diagnosed, microscopically
      invasive breast cancer by receptor status: Iowa SEER 2000 to 2013.
AB  - BACKGROUND: Recent incidence, treatment patterns, and outcomes for node negative
      microscopically invasive breast cancer (MIBC) have not been reported. METHODS:
      State Health Registry of Iowa data identified women with ductal carcinoma in situ
      (DCIS), MIBC, and stage I breast cancer excluding MIBC (stage 1BC). RESULTS: From
      2000 to 2013, 1,706, 193, and 4,514 women were diagnosed with DCIS, MIBC, and
      stage 1BC, respectively. MIBC increased at an annual percentage change of 2.1 (P
      = .041). MIBC was more frequently human epidermal growth factor receptor 2
      positive than stage 1BC (39.7% vs 9.6%, P < .001). Mastectomy was performed more
      frequently in MIBC than DCIS (40.9% vs 30.6%, P = .014) or stage 1BC (40.9% vs
      33.8%, P = .119). Chemotherapy was given to 4.1% of women with MIBC. Survival for
      women with MIBC was intermediate between DCIS and stage 1BC. CONCLUSIONS:
      Management of MIBC is an increasingly frequent clinical scenario. Women with MIBC
      receive more aggressive local and systemic therapy than women with DCIS.

PMID- 27692794
TI  - Outcomes and feasibility of nipple-sparing mastectomy for node-positive breast
      cancer Patients.
AB  - BACKGROUND: While nipple-sparing mastectomy (NSM) is gaining acceptance for risk
      reduction and for treatment of early stage breast cancer, node-positive disease
      remains a relative contraindication. Our aim was to evaluate the use and outcomes
      of NSM in node-positive breast cancer patients. METHODS: We identified 240
      cancers in 226 patients (14 bilateral) scheduled for NSM and operated on between
      1/2009 and 6/2014. We compared outcomes for 58 node-positive vs 182 node-negative
      patients. RESULTS: Intraoperative conversion to skin-sparing mastectomy was
      similar for node-positive and node-negative patients, 10% and 7%, as was 1-year
      success of NSM, 84% and 90%, respectively. Five-year locoregional disease-free
      estimates were 82% (95% CI 68%-99%) for node-positive and 99% (95% CI 96%-100%)
      for node-negative patients, P = .004; however, there were no nipple-areolar
      recurrences among node-positive patients. CONCLUSIONS: With careful consideration
      of biologic and anatomic risk factors for recurrence, these data suggest that NSM
      is a reasonable option for selected node-positive breast cancer patients.

PMID- 27692795
TI  - Ontogenetic shifts in the diet of plains hog-nosed snakes (Heterodon nasicus)
      revealed by stable isotope analysis.
AB  - Wild snake diets are difficult to study using traditional methods, but stable
      isotopes offer several advantages, including integrating dietary information over
      time, providing data from individuals that have not fed recently, and avoiding
      bias towards slowly-digesting prey items. We used stable isotope signatures of
      carbon and nitrogen from scale tissue, red blood cells, and blood plasma to
      assess the diet of wild plains hog-nosed snakes (Heterodon nasicus) in Illinois.
      We developed Bayesian mixing models which, taken together, predicted that H.
      nasicus shifted from a juvenile diet predominantly (31-63%) composed of six-lined
      racerunners (Aspidoscelis sexlineatus) and their eggs to an adult diet
      predominantly (44-56%) composed of eggs of the aquatic turtles Chrysemys picta
      and Chelydra serpentina, with a contribution from toads (Anaxyrus sp.; 6-27%)
      during their adolescent years. These results agreed with sparse data from gut
      contents. Combining traditional and isotopic techniques for studying the diets of
      wild snakes can increase the utility of both types of data.

PMID- 27692796
TI  - Pupillometry registers toddlers' sensitivity to degrees of mispronunciation.
AB  - This study introduces a method ideally suited for investigating toddlers' ability
      to detect mispronunciations in lexical representations: pupillometry. Previous
      research has established that the magnitude of pupil dilation reflects differing
      levels of cognitive effort. Building on those findings, we use pupil dilation to
      study the level of detail encoded in lexical representations with 30-month-old
      children whose lexicons allow for a featurally balanced stimulus set. In each
      trial, we present a picture followed by a corresponding auditory label. By
      systematically manipulating the number of feature changes in the onset of the
      label (e.g., baby~daby~faby~shaby), we tested whether featural distance predicts
      the degree of pupil dilation. Our findings support the existence of a
      relationship between featural distance and pupil dilation. First, mispronounced
      words are associated with a larger degree of dilation than correct forms. Second,
      words that deviate more from the correct form are related to a larger dilation
      than words that deviate less. This pattern indicates that toddlers are sensitive
      to the degree of mispronunciation, and as such it corroborates previous work that
      found word recognition modulated by sub-segmental detail and by the degree of
      mismatch. Thus, we establish that pupillometry provides a viable alternative to
      paradigms that require overt behavioral response in increasing our understanding
      of the development of lexical representations.

PMID- 27692797
TI  - Cardiovascular complications and mortality determinants in near drowning victims:
      A 5-year retrospective analysis.

PMID- 27692798
TI  - Biomechanical responses to changes in friction on a clay court surface.
AB  - OBJECTIVES: To examine the influence of clay court frictional properties on
      tennis players' biomechanical response. DESIGN: Repeated measures. METHODS: Lower
      limb kinematic and force data were collected on sixteen university tennis players
      during 10*180 degrees  turns (running approach speed 3.9+/-0.20ms-1) on a
      synthetic clay surface of varying friction levels. To adjust friction levels the
      volume of sand infill above the force plate was altered (kg per m2 surface area;
      12, 16 and 20kgm-2). Repeated measures ANOVA and Bonferroni's corrected alpha
      post-hoc analyses were conducted to identify significant differences in lower
      limb biomechanics between friction levels. RESULTS: Greater sliding distances
      (etap2=0.355, p=0.008) were observed for the lowest friction condition (20kgm-2)
      compared to the 12 and 16kgm-2 conditions. No differences in ankle joint
      kinematics and knee flexion angles were observed. Later peak knee flexion
      occurred on the 20kgm-2 condition compared to the 12kgm-2 (etap2=0.270, p=0.023).
      Lower vertical (etap2=0.345, p=0.027) and shear (etap2=0.396, p=0.016) loading
      rates occurred for the 20kgm2 condition compared to the 16kgm2. CONCLUSIONS:
      Lower loading rates and greater sliding distances when clay surface friction was
      reduced suggests load was more evenly distributed over time reducing players'
      injury risks. The greater sliding distances reported were accompanied with later
      occurrence of peak knee flexion, suggesting longer time spent braking and a
      greater requirement for muscular control increasing the likelihood of fatigue.

PMID- 27692799
TI  - Human fibroblasts treated with hydrogen peroxide stimulate human melanoblast
      proliferation and melanocyte differentiation, but inhibit melanocyte
      proliferation in serum-free co-culture system.
AB  - BACKGROUND: Oxidative stress caused by hydrogen peroxide (H2O2) elicits harmful
      effects on human melanocytes such as DNA damage and cell death. On the contrary,
      H2O2 is known to possess beneficial effects on melanocytes. However, mechanisms
      of the beneficial effects of H2O2 on melanocytes have not been fully understood,
      especially the indirect effects on melanocyte proliferation and differentiation
      from cells constituting surrounding tissue environment such as fibroblasts.
      OBJECTIVE: The aim of this study was to clarify whether H2O2-treated human
      fibroblasts affect the proliferation and differentiation of human melanocytes
      using serum-free co-culture system. METHODS: Epidermal melanoblasts and
      melanocytes were co-cultured with H2O2-treated or control fibroblasts in serum
      free culture media. The effects of H2O2-treated fibroblasts were detected by
      changes in the proliferation and differentiation of melanoblasts/melanocytes.
      RESULTS: H2O2-treated fibroblasts stimulated the proliferation of melanoblasts
      and the differentiation, melanogenesis, and dendritogenesis of melanocytes, but
      inhibited the proliferation of melanocytes. In the melanocytes co-cultured with
      H2O2-treated fibroblasts, the expression of tyrosinase (TYR), tyrosinase-related
      protein 1 (TYRP1), and KIT was increased, whereas TYRP2 and microphthalmia
      associated transcription factor showed no change. CONCLUSION: These results
      suggest that H2O2-treated fibroblasts can produce and release some mitogenic and
      melanogenic factors toward melanoblasts in addition to some proliferation
      inhibiting factors toward melanocytes. The stimulation of melanocyte
      differentiation seems to be performed through the upregulation of TYR, TYRP1, and
      KIT.

PMID- 27692800
TI  - Sex biology contributions to vulnerability to Alzheimer's disease: A think tank
      convened by the Women's Alzheimer's Research Initiative.
AB  - More than 5 million Americans are living with Alzheimer's disease (AD) today, and
      nearly two-thirds of Americans with AD are women. This sex difference may be due
      to the higher longevity women generally experience; however, increasing evidence
      suggests that longevity alone is not a sufficient explanation and there may be
      other factors at play. The Alzheimer's Association convened an expert think tank
      to focus on the state of the science and level of evidence around gender and
      biological sex differences for AD, including the knowledge gaps and areas of
      science that need to be more fully addressed. This article summarizes the think
      tank discussion, moving forward a research agenda and funding program to better
      understand the biological underpinnings of sex- and gender-related disparities of
      risk for AD.

PMID- 27692801
TI  - Risk of Prolonged Opioid Use Among Opioid-Naive Patients Following Common Hand
      Surgery Procedures.
AB  - PURPOSE: To evaluate prolonged opioid use in opioid-naive patients after common
      hand surgery procedures in the United States. METHODS: We studied insurance
      claims from the Truven MarketScan databases to identify opioid-naive adult
      patients (no opioid exposure 11 months before the perioperative period) who
      underwent an elective (carpal tunnel release, carpometacarpal
      arthroplasty/arthrodesis, cubital tunnel release, or trigger finger release) or
      trauma-related (closed distal radius fracture fixation, flexor tendon repair,
      metacarpal fracture fixation, or phalangeal fracture fixation) hand surgery
      procedure between 2010 and 2012 (N = 77,573 patients). Patients were observed for
      6 months to determine the number, timing, duration, and oral morphine equivalent
      dosage of postoperative opioid prescriptions. We assessed prolonged postoperative
      opioid use, defined as patients who filled a perioperative opioid prescription
      followed by a prescription between 90 and 180 days after surgery, and evaluated
      associated risk factors using multivariable logistic regression. RESULTS: In this
      cohort, 59,725 opioid-naive patients (77%) filled a perioperative opioid
      prescription. Of these, 13% of patients continued to fill prescriptions between
      90 and 180 days after surgery. Elective surgery patients were more likely to
      continue to fill opioid prescriptions after 90 days compared with trauma patients
      (13.5% vs 10.5%). Younger age, female gender, lower income, comprehensive
      insurance, higher Elixhauser comorbidity index, mental health disorders, and
      tobacco dependence or abuse were associated with prolonged opioid use.
      CONCLUSIONS: Approximately 13% of opioid-naive patients continue to fill opioid
      prescriptions after hand surgery procedures 90 days after surgery. Preoperative
      interventions centered on opioid alternatives and early cessation, particularly
      among patients at risk for long-term use, is critical to addressing the
      prescription opioid crisis in the United States. CLINICAL RELEVANCE: The current
      national opioid use epidemic requires an assessment of the prevalence of hand
      surgery patients who receive and fill opioid prescriptions after common hand
      surgery procedures.

PMID- 27692802
TI  - Molecular characteristics and antimicrobial resistance in invasive and
      noninvasive Group B Streptococcus between 2008 and 2015 in China.
AB  - Group B streptococcus (GBS) is an increasing pathogen threat to newborns and
      adults with immunodepressive diseases. Here, a total of 193 GBS, including 51
      invasive and 142 noninvasive isolates, were collected from the patients with
      infections in 7 tertiary hospitals from 5 cities in China during the year 2008 to
      2015. The strains of GBS were characterized by classical and molecular techniques
      for capsular polysaccharide serotyping, genes for pilus island (PI) and alpha
      like protein (alp), and antibiotic resistance profiling. Of 193 isolates, the
      predominant serotypes were III (45.6%) and Ia (18.7%). All strains carried at
      least 1 PI gene. The combination of PI-2b and PI-1 was present in 46.1% isolates,
      followed by PI-2a alone (80, 41.5%) and PI-2b alone (23, 11.9%). The most
      prevalent alp gene was rib (87, 45.1%), followed by alpha-C (47, 24.4%), epsilon
      (33, 17.1%), alp2/3 (7, 3.6%) and alp4 (2, 1.0%), respectively. The clonal
      relationships between strains were investigated using multilocus sequence typing.
      The strains were distinguished into 26 individual sequence typing, and further
      clustered into 6 clonal complexes. A significant association was noted between
      the distributions of alp genes, serotyping and PI profiles, such as serotype III
      rib-PI+PI-2a, Ib-alpha-C, and Ia-epsilon-PI-2a. No penicillin-resistant strains
      were detected, and 74.1%, 64.2%, and 68.9% were resistant to erythromycin,
      clindamycin, and tetracycline, respectively. The infective GBS isolates in China
      demonstrated epidemical features.

PMID- 27692803
TI  - Extraordinary Survival: What Does It Take?

PMID- 27692804
TI  - [Simple method for determining the size of the ProSeal laryngeal mask airway in
      children: a prospective observational study].
AB  - BACKGROUND AND OBJECTIVES: The size of the ProSeal laryngeal mask airway in
      children is determined by the patient's weight. However, in some instances, an
      alternative method may be required. This study aimed to compare sizing by the
      auricle with conventional ProSeal laryngeal mask airway sizing by weight in
      children. METHODS: After approval by the institutional ethics board and written
      informed consent from parents, 197 children with American Society of
      Anesthesiologists physical status I-II who were scheduled for a routine
      genitourinary operation were included in the study. The correct ProSeal laryngeal
      mask airway size was determined according to the size of the auricle in children.
      The results were compared with the standard weight-based method recommended by
      the manufacturer's guidelines. The patients were classified into different groups
      depending on the ProSeal laryngeal mask airway sizes as determined by both
      methods. Agreement between both techniques was evaluated with kappa coefficient
      statistics. RESULTS: Insertion and adequate ventilation were achieved in 185
      patients at the first attempt, and 12 patients required a second attempt. Three
      patients had to be intubated. Agreement between the two methods of size selection
      of the ProSeal laryngeal mask airway was moderate using kappa statistics.
      CONCLUSIONS: Choosing the size of the ProSeal laryngeal mask airway in children
      according to the auricle of the child is valid and practical. In particular, this
      is an alternative method in situations where the patient's weight is unknown,
      such as in emergency situations.

PMID- 27692805
TI  - [Design and validation of an oral health questionnaire for preoperative
      anaesthetic evaluation].
AB  - BACKGROUND AND OBJECTIVES: Dental injuries incurred during endotracheal
      intubation are more frequent in patients with previous oral pathology. The study
      objectives were to develop an oral health questionnaire for preanaesthesia
      evaluation, easy to apply for personnel without special dental training; and
      establish a cut-off value for detecting persons with poor oral health. METHODS:
      Validation study of a self-administered questionnaire, designed according to a
      literature review and an expert group's recommendations. The questionnaire was
      applied to a sample of patients evaluated in a preanaesthesia consultation. Rasch
      analysis of the questionnaire psychometric properties included viability,
      acceptability, content validity and reliability of the scale. RESULTS: The sample
      included 115 individuals, 50.4% of men, with a median age of 58 years (range: 38
      71). The final analysis of 11 items presented a Person Separation Index of 0.861
      and good adjustment of data to the Rasch model. The scale was unidimensional and
      its items were not biased by sex, age or nationality. The oral health linear
      measure presented good construct validity. The cut-off value was set at 52
      points. CONCLUSIONS: The questionnaire showed sufficient psychometric properties
      to be considered a reliable tool, valid for measuring the state of oral health in
      preoperative anaesthetic evaluations.

PMID- 27692807
TI  - Image-Rich Radiology Reports: A Value-Based Model to Improve Clinical Workflow.
AB  - PURPOSE: To determine the value of image-rich radiology reports (IRRR) by
      evaluating the interest and preferences of referring physicians, potential impact
      on clinical workflow, and the willingness of radiologists to create them.
      METHODS: Referring physicians and radiologists were interviewed in this
      prospective, HIPAA-compliant study. Subject willingness to participate in the
      study was determined by an e-mail. A single investigator conducted all interviews
      using a standard questionnaire. All subjects reviewed a video mockup
      demonstration of IRRR and three methods for viewing embedded images, as follows:
      (1) clickable hyperlinks to access a scrollable stack of images, (2) scrollable
      and enlargeable small-image thumbnails, and (3) scrollable but not enlargeable
      medium-sized images. Questionnaire responses, free comments, and general
      impressions were captured and analyzed. RESULTS: Seventy-two physicians (36
      clinicians, 36 radiologists) were interviewed. Thirty-one clinicians (86%)
      expressed interest in using IRRR. Seventy-seven percent of subjects believed IRRR
      would improve communication. Ten clinicians (28%) preferred method 1, 18 (50%)
      preferred method 2, and 8 (22%) preferred method 3 for embedding images. Thirty
      clinicians (83%) stated that IRRR would improve efficiency. Twenty-two
      radiologists (61%) preferred selecting a tool button with a mouse and right
      clicking images to embed them, 13 (36%) preferred pressing a function key, and 11
      (31%) preferred dictating series and image numbers. The average time radiologists
      were willing to expend for embedding images was 66.7 seconds. CONCLUSIONS:
      Referring physicians and radiologist both believe IRRR would add value by
      improving communication with the potential to improve the workflow efficiency of
      referring physicians.

PMID- 27692808
TI  - Surgery Clerkship Evaluations Are Insufficient for Clinical Skills Appraisal: The
      Value of a Medical Student Surgical Objective Structured Clinical Examination.
AB  - OBJECTIVE: Optimal methods for medical student assessment in surgery remain
      elusive. Faculty- and housestaff-written evaluations constitute the chief means
      of student assessment in medical education. However, numerous studies show that
      this approach has poor specificity and a high degree of subjectivity. We
      hypothesized that an objective structured clinical examination (OSCE) in the
      surgery clerkship would provide additional data on student performance that would
      confirm or augment other measures of assessment. DESIGN: We retrospectively
      reviewed data from OSCEs, National Board of Medical Examiners shelf examinations,
      oral presentations, and written evaluations for 51 third-year Harvard Medical
      School students rotating in surgery at Massachusetts General Hospital from 2014
      to 2015. We expressed correlations between numeric variables in Pearson
      coefficients, stratified differences between rater groups by one-way analysis of
      variance, and compared percentages with 2-sample t-tests. We examined commentary
      from both OSCE and clinical written evaluations through textual analysis and
      summarized these results in percentages. RESULTS: OSCE scores and clinical
      evaluation scores correlated poorly with each other, as well as with shelf
      examination scores and oral presentation grades. Textual analysis of clinical
      evaluation comments revealed a heavy emphasis on motivational factors and praise,
      whereas OSCE written comments focused on cognitive processes, patient management,
      and methods to improve performance. CONCLUSIONS: In this single-center study, an
      OSCE provided clinical skills data that were not captured elsewhere in the
      surgery clerkship. Textual analysis of faculty evaluations reflected an emphasis
      on interpersonal skills, rather than appraisal of clinical acumen. These findings
      suggest complementary roles of faculty evaluations and OSCEs in medical student
      assessment.

PMID- 27692806
TI  - Human vascular progenitor cells derived from renal arteries are endothelial-like
      and assist in the repair of injured renal capillary networks.
AB  - Vascular progenitor cells show promise for the treatment of microvasculature
      endothelial injury. We investigated the function of renal artery progenitor cells
      derived from radical nephrectomy patients, in animal models of acute ischemic and
      hyperperfusion injuries. Present in human adventitia, CD34positive/CD105negative
      cells were clonal and expressed transcription factors Sox2/Oct4 as well as
      surface markers CXCR4 (CD184)/KDR(CD309) consistent with endothelial progenitor
      cells. Termed renal artery-derived vascular progenitor cells (RAPC), injected
      cells were associated with decreased serum creatinine after ischemia/reperfusion,
      reduced albuminuria after hyperperfusion, and improved blood flow in both models.
      A small population of RAPC integrated with the renal microvasculature following
      either experimental injury. At a cellular level, RAPC promoted local endothelial
      migration in co-culture. Profiling of RAPC microRNA identified high levels of
      miRNA 218; also found at high levels in exosomes isolated from RAPC conditioned
      media after cell contact for 24 hours. After hydrogen peroxide-induced
      endothelial injury, RAPC exosomes harbored Robo-1 transcript; a gene known to be
      regulated by mir218. Such exosomes enhanced endothelial cell migration in culture
      in the absence of RAPC. Thus, our work shows the feasibility of pre-emptive pro
      angiogenic progenitor cell procurement from a targeted patient population and
      potential therapeutic use in the form of autologous cell transplantation.

PMID- 27692809
TI  - Awareness of Surgeons in Saudi Arabia About the Surgical Costs and
      Investigations: Multicenter Study.
AB  - OBJECTIVE: To investigate the level of knowledge and awareness of the cost of the
      currently used blood investigations, imaging studies, admission cost, and
      surgical instrument among surgeons in Saudi Arabia. DESIGN: It was a cross
      section study conducted in Riyadh city, the capital of Saudi Arabia. SETTING:
      Multihealth centers including main University hospital, Military hospitals, and
      Ministry of health hospitals. All surgeons in the health facilities were invited
      to participate in the study. A questionnaire has been formulated, and distributed
      to all participants. It was composed of 3 sections such as: demographic data,
      awareness about the cost, and physicians' perception about the cost and the
      attitude of their institution toward cost practice. RESULT: Totally, 296
      participants were enrolled in the study. More than half of the respondents were
      females (53.3%). Nearly two-thirds were in the young age group (30-40 years),
      41.2% were residents. Only 4.4%, 3.4%, 8.4%, and 3.7% of the surgeons were fully
      aware of the cost of blood investigations, imaging studies, surgical
      instruments/prosthesis, and the medication that they prescribe, respectively.
      Most of them mentioned that their institute neither encourages them to consider a
      cost-effective practice (86.9%) nor monitor how cost effective is their practice
      (86.2%). CONCLUSION: Surgeon's knowledge and awareness about the cost of
      different medical procedures were insufficient. Surgeons' knowledge and attitudes
      about costs of care can be improved through the use of audit and feedback with
      patient cost and charge data, which could be attained through the inclusion of
      audit and feedback as part of a curriculum teaching.

PMID- 27692810
TI  - Effect of Bleomycin Administration on the Development of Pulmonary Toxicity in
      Patients With Metastatic Germ Cell Tumors Receiving First-Line Chemotherapy: A
      Meta-Analysis of Randomized Studies.
AB  - BACKGROUND: Limited information is available about the effect of bleomycin
      administration on the development of pulmonary toxicity in metastatic germ cell
      tumors (GCT). PATIENTS AND METHODS: A literature search was conducted to identify
      randomized trials of first-line chemotherapy for GCT. We conducted univariate and
      multivariate analyses using random effects models to evaluate the predictive role
      of bleomycin administration in the development of all Grade and Grade 3 to 4 (G3
      4) pulmonary toxicity. The results were adjusted for length of follow-up,
      prognostic risk group, year of treatment, presence of lung metastases, and
      primary mediastinal GCT. RESULTS: Fifty-three study arms of 25 phase II and III
      trials encompassing 6498 patients were selected: 40 that used bleomycin (n =
      5093) and 13 that did not (n = 1405). The pooled probability of all-Grade
      pulmonary toxicity in the bleomycin and nonbleomycin arms was 11.7% (95%
      confidence interval [CI], 8.4%-16.0%) and 1.7% (95% CI, 0.7%-4.2%), respectively.
      Univariate analysis indicated that bleomycin administration was associated with
      the incidence of all-Grade (odds ratio [OR], 7.57; 95% CI, 2.84-20.18; Wald test
      P < .001) and G3-4 pulmonary toxicity (OR, 5.19; 95% CI, 1.57-17.16; P = .007).
      Multivariate analysis showed a significant association of bleomycin
      administration with the incidence of all-Grade pulmonary toxicity (OR, 4.14; 95%
      CI, 1.36-12.59; P = .012) and a trend toward significance for G3-4 toxicity (OR,
      2.24; 95% CI, 0.91-5.51; P = .080). CONCLUSION: We quantified the bleomycin
      associated effect on the development of pulmonary toxicity in patients with GCT
      who received first-line chemotherapy. This information might be useful for
      planning clinical trials aimed at reducing chemotherapy as well as to inform
      patients in the clinic.

PMID- 27692811
TI  - Clinical Impact of the Number of Treatment Cycles in First-Line Docetaxel for
      Patients With Metastatic Castration-Resistant Prostate Cancer.
AB  - BACKGROUND: We investigated the impact of the number of docetaxel cycles
      administered in patients with metastatic castration-resistant prostate cancer
      (mCRPC) treated with first-line chemotherapy. PATIENTS AND METHODS: Charts from
      421 consecutive patients who initiated standard treatment with docetaxel-based
      chemotherapy (75 mg/m2 every 3 weeks) between 2007 and 2013 were reviewed.
      Patients who received < 6 cycles of docetaxel were excluded from the analysis.
      Remaining patients were divided into 2 groups on the basis of whether or not >= 9
      cycles of docetaxel were administered (n = 108 and 184, respectively). Reasons
      for treatment discontinuation and postdocetaxel treatments were registered.
      Prostate-specific antigen (PSA) responses were defined as a confirmed >= 50%
      decrease in baseline PSA levels. Overall survival (OS) was calculated from start
      of therapy using the Kaplan-Meier method. Cox proportional hazards were
      calculated to estimate the effect of clinical variables on OS. RESULTS: OS was
      longer in patients treated with >= 9 cycles of docetaxel (21.9 months vs. 17.2
      months; P < .0001, log rank). Survival also favored patients treated with >= 9
      cycles of docetaxel when only patients ending docetaxel because of toxicity or
      treatment conclusion (22.3 vs. 19.4 months; P = .048, log rank) or patients who
      achieved a PSA response (22.3 vs. 18.7 months; P = .012, log rank) were
      evaluated. mCRPC-related prognostic factors and patients who received >= 1
      subsequent line of therapy post-docetaxel were well balanced. CONCLUSION: On the
      basis of our retrospective findings, a superior OS was found in patients treated
      with >= 9 cycles of docetaxel when adjusting for known prognostic factors. Dose
      reductions might increase the number of docetaxel cycles administered.

PMID- 27692813
TI  - Prolonged Remission of Upper Urinary Tract Urothelial Carcinoma With Prominent
      Choriocarcinomatous Differentiation: A Case Report.

PMID- 27692814
TI  - Concomitant and discrete expressions of aldose reductase and sorbitol
      dehydrogenase in the male reproductive tract.
AB  - This study aimed at investigating the expression and localization of the polyol
      pathway enzymes; aldose reductase (AR) and sorbitol dehydrogenase (SDH), in the
      male reproductive tract of rat. Gene expression analysis showed maximum
      expression of AR and SDH in the coagulating glands. Western blot analysis showed
      a coordinated presence of the two enzymes in the coagulating glands, seminal
      vesicle and epididymis. Immunohistochemistry showed a concordant expression of
      the two enzymes in the coagulating gland, which goes well with its function of
      fructose production in rats. A less concordant expression of the two enzymes in
      the seminal vesicle was also seen. Discrete expression of AR was seen in the
      Sertoli cells without SDH. Germ cells including sperm in the seminiferous tubules
      lacked AR, but SDH was present in all stages of developing germ cells including
      sperm present in the seminiferous tubules. The epithelial layer of epididymis
      showed the presence of AR, but it was negligible in vas deferens and prostate.
      SDH was not seen in the epithelial layer of epididymis, vas deferens or prostate.
      Though sperm in the seminiferous tubules lacked AR, sperm extracted from cauda
      showed the presence of both AR and SDH. Immunofluorescence localization of AR and
      SDH on sperm showed the presence of both the enzymes all over sperm. Discrete
      expression of AR in the Sertoli cells may be linked to detoxification of a number
      of metabolism by-products. Similarly, the presence of polyol enzymes on sperm in
      epididymis and beyond may be to tackle toxic metabolites they may encounter
      during their journey along the male or female reproductive tract.

PMID- 27692812
TI  - Predicting Time From Metastasis to Overall Survival in Castration-Resistant
      Prostate Cancer: Results From SEARCH.
AB  - OBJECTIVE: To identify the predictors of time from initial diagnosis of
      metastatic castration-resistance prostate cancer (mCRPC) to all-cause death
      within the Shared Equal Access Regional Cancer Hospital cohort. PATIENTS AND
      METHODS: We performed a retrospective analysis of 205 mCRPC men. Overall survival
      was estimated and plotted using the Kaplan-Meier method. The uni- and
      multivariable overall survival predictors were evaluated with the Cox
      proportional hazards model. A nomogram was generated to predict overall survival
      at 1, 2, 3, and 5 years after mCRPC. Concordance index and calibration plot were
      obtained. RESULTS: A total of 170 men (83%) died over a median follow-up of 41
      months. In univariable analysis, older age, more remote year of mCRPC, nonblack
      race, greater number of bone metastasis, higher prostate-specific antigen (PSA)
      levels, shorter PSA doubling time, and faster PSA velocity at mCRPC diagnosis
      were significantly associated with shorter overall survival (all P < .05). In
      multivariable analysis, older age, more remote year of mCRPC, greater number of
      bone metastasis, higher PSA levels, and shorter PSA doubling time at mCRPC
      diagnosis remained significantly associated with shorter overall survival (all P
      < .05). On the basis of these variables, a nomogram was generated yielding a
      concordance index of 0.67 and good calibration. CONCLUSION: The use of clinical
      parameter such as age, disease burden, and PSA levels and kinetics can be used to
      estimate overall survival in mCRPC patients.

PMID- 27692816
TI  - From bench to pet shop to bedside? The environment and immune function in mice.
AB  - The generation of inbred mouse strains in the late 19th and early 20th centuries,
      coupled with the later establishment of specific pathogen-free animal research
      facilities created a powerful biological platform for exploration of the immune
      system in health and disease. Studies in this setting have been responsible for
      huge advances in our understanding of immunobiology and disease, including immune
      mediated kidney disease. However, whereas this reductionist and relatively
      standardized approach allows us to make sense of complex disease biology, it
      takes place in controlled environments that clearly differ from those that we
      humans encounter in everyday life. Recent studies comparing the immune systems of
      wild mice, pet shop mice, and laboratory mice suggest ways in which the murine
      immune system can be influenced to behave more like the human immune system.

PMID- 27692815
TI  - Targeted disruption of Cd40 in a genetically hypertensive rat model attenuates
      renal fibrosis and proteinuria, independent of blood pressure.
AB  - High blood pressure is a common cause of chronic kidney disease. Because CD40, a
      member of the tumor necrosis factor receptor family, has been linked to the
      progression of kidney disease in ischemic nephropathy, we studied the role of
      Cd40 in the development of hypertensive renal disease. The Cd40 gene was mutated
      in the Dahl S genetically hypertensive rat with renal disease by targeted-gene
      disruption using zinc-finger nuclease technology. These rats were then given low
      (0.3%) and high (2%) salt diets and compared. The resultant Cd40 mutants had
      significantly reduced levels of both urinary protein excretion (41.8 +/- 3.1
      mg/24 h vs. 103.7 +/- 4.3 mg/24 h) and plasma creatinine (0.36 +/- 0.05 mg/dl vs.
      1.15 +/- 0.19 mg/dl), with significantly higher creatinine clearance compared
      with the control S rats (3.04 +/- 0.48 ml/min vs. 0.93 +/- 0.15 ml/min),
      indicating renoprotection was conferred by mutation of the Cd40 locus.
      Furthermore, the Cd40 mutants had a significant attenuation in renal fibrosis,
      which persisted on the high salt diet. However, there was no difference in
      systolic blood pressure between the control and Cd40 mutant rats. Thus, these
      data serve as the first evidence for a direct link between Cd40 and hypertensive
      nephropathy. Hence, renal fibrosis is one of the underlying mechanisms by which
      Cd40 plays a crucial role in the development of hypertensive renal disease.

PMID- 27692818
TI  - The Nidus for Possible Thrombus Formation: Insight From the Microenvironment of
      Bioresorbable Vascular Scaffold.

PMID- 27692819
TI  - Diagnostic, Therapeutic, and Clinical Trial Conundrum of Patients With Chronic
      Kidney Disease.

PMID- 27692817
TI  - An overview of renal metabolomics.
AB  - The high-throughput, high-resolution phenotyping enabled by metabolomics has been
      applied increasingly to a variety of questions in nephrology research. This
      article provides an overview of current metabolomics methodologies and
      nomenclature, citing specific considerations in sample preparation, metabolite
      measurement, and data analysis that investigators should understand when
      examining the literature or designing a study. Furthermore, we review several
      notable findings that have emerged in the literature that both highlight some of
      the limitations of current profiling approaches, as well as outline specific
      strengths unique to metabolomics. More specifically, we review data on the
      following: (i) tryptophan metabolites and chronic kidney disease onset,
      illustrating the interpretation of metabolite data in the context of established
      biochemical pathways; (ii) trimethylamine-N-oxide and cardiovascular disease in
      chronic kidney disease, illustrating the integration of exogenous and endogenous
      inputs to the blood metabolome; and (iii) renal mitochondrial function in
      diabetic kidney disease and acute kidney injury, illustrating the potential for
      rapid translation of metabolite data for diagnostic or therapeutic aims. Finally,
      we review future directions, including the need to better characterize
      interperson and intraperson variation in the metabolome, pool existing data sets
      to identify the most robust signals, and capitalize on the discovery potential of
      emerging nontargeted methods.

PMID- 27692821
TI  - Extraordinary Subintimal Bleeding After Coronary Stenting.

PMID- 27692822
TI  - A New Hope on Treatment of Atrial Dissection Complicated by Mitral Annulus
      Rupture: The First Case of Percutaneous Treatment.

PMID- 27692820
TI  - Chronic Kidney Disease in the Second-Generation Drug-Eluting Stent Era: Pooled
      Analysis of the Korean Multicenter Drug-Eluting Stent Registry.
AB  - OBJECTIVES: The purpose of this study was to evaluate the clinical impact of
      chronic kidney disease (CKD) on clinical outcomes in contemporary practice of
      percutaneous coronary intervention (PCI) using second-generation drug-eluting
      stents (DES). BACKGROUND: Although second-generation DES have improved the safety
      and efficacy issues in PCI, data regarding the performance of second-generation
      DES in patients with CKD are still limited. METHODS: We performed a patient-level
      pooled analysis on 12,426 patients undergoing PCI using second-generation DES
      from the Korean Multicenter Drug-Eluting Stent Registry. Endpoints were stent
      oriented outcomes (target lesion failure [TLF]) and patient-oriented composite
      outcomes (POCO) during a median follow-up of 35 months. CKD patients were
      stratified by the estimated glomerular filtration rate (eGFR) from mild CKD to
      end-stage renal disease patients, and by the coexistence of diabetes mellitus
      (DM). RESULTS: A total of 2,927 patients had CKD (23.6%), who showed a
      significantly higher risk of TLF (adjusted hazard ratio [HRadjust]: 1.50; 95%
      confidence interval [CI]: 1.21 to 1.86) and POCO (HRadjust 1.34; 95% CI: 1.17 to
      1.55) compared to patients with preserved renal function. Stratified analysis by
      eGFR showed that TLF was not increased in the mild to moderate CKD, whereas
      severe CKD and dialysis-dependent patients showed significantly higher risk of
      TLF (HRadjust 2.44; 95% CI: 1.54 to 3.86; HRadjust 3.58; 95% CI: 2.52 to 5.08,
      respectively). The eGFR threshold of increased clinical events was 40 to 45
      ml/min/1.73 m2. Among CKD patients, DM CKD patients showed a higher incidence of
      TLF compared to non-DM CKD patients (HRadjust: 1.82; 95% CI: 1.32 to 2.52),
      driven by the increase in target vessel-related events. CONCLUSIONS: In the era
      of second-generation DES, CKD patients were at a significantly higher risk of
      clinical outcomes only in severe CKD and end-stage renal disease patients.

PMID- 27692823
TI  - Transcaval Transcatheter Aortic Valve Replacement With the ACURATE-neo Aortic
      Bioprosthesis: First North American Experience.

PMID- 27692824
TI  - [Assessment of screening for Down syndrome in Martinique from 2011 to 2013: An
      island location favoured].
AB  - OBJECTIVES: The aim of this study is to evaluate the screening for trisomy 21
      (T21) between 2011 and 2013 on Martinique French West Indies after the decree of
      23 June 2009. MATERIALS AND METHODS: Were used the prenatal data provided by
      accredited laboratories and the data from the Registry of Congenital French West
      Indies (REMALAN). RESULTS: A total of 85.9 % of patients underwent screening:
      60.5 % on a combined calculation of risk (CRC), 14.6 % on a sequential
      calculation of risk (CRS) and 10.8 % on serum markers 2nd trimester (MST2).
      Overall 5.4 % of the patients were placed in a risk group. During this period, 47
      trisomy 21 were identified by the REMALAN which 38 (80.1 %) were detected
      prenatally: 24 of CRC, 3 on MST2 and 11 on signs of ultrasound at the 1st and 2nd
      trimester. The sensitivity of the CRC was 88 % for a false positive rate of 3.87
      %. The overall sensitivity of screening (CRC, CRS and MST2) was 87 % for a false
      positive rate of 5.21 %. CONCLUSION: These data show that the coverage rate in
      Martinique is satisfactory and the screening fir Down syndrome meet expectations.

PMID- 27692825
TI  - Establishing Age-Specific Cost-Effective Annual Revision Rates for
      Unicompartmental Knee Arthroplasty: A Meta-Analysis.
AB  - BACKGROUND: Improved survivorship has contributed to the increased use of
      unicompartmental knee arthroplasty (UKA) as an alternative to total knee
      arthroplasty (TKA) for unicompartmental knee osteoarthritis. However,
      heterogeneity among cost-effectiveness analysis studies comparing UKA to TKA has
      prevented the derivation of discrete implant survivorship targets. The aim of
      this meta-analysis was to determine the age-stratified annual revision rate (ARR)
      threshold for UKA to become consistently cost-effective for unicompartmental knee
      osteoarthritis. METHODS: A systematic search was performed for cost-effectiveness
      analysis studies of UKA vs TKA. Selected publications were rated by evidence
      level and assessed for methodological quality. Target UKA survivorship values
      determined by sensitivity analysis were retrieved, converted to ARR, and combined
      by age category (<65, 65-74, and >=75 years) to estimate age-specific cost
      effectiveness thresholds. RESULTS: Four studies met all inclusion criteria. All
      publications were evidence level I-B, with high methodological quality. Combined
      data indicated median threshold cost-effective ARR of 1.471% (interquartile range
      [IQR], 1.415-1.833; age <65), 1.135% (IQR, 1.011-1.260; age 65-74), and 1.760%
      (IQR, 1.660-2.880; age >=75). Current revision rates are already below the cost
      effective threshold for patients aged >=75, but exceed recommended values in
      younger patients. CONCLUSION: The findings indicate that implant survivorship is
      a limiting factor toward achieving cost-effective UKA in patients aged <65.
      Strategies to improve UKA survivorship, such as shifting procedures to high
      volume centers, may render UKA cost-effective in younger patients. This presents
      an opportunity for resource reallocation within health systems to achieve cost
      effective utilization of UKA across a broader population segment.

PMID- 27692826
TI  - [Encephalopathy and influenza virus].

PMID- 27692827
TI  - [Finegoldia magna endocarditis].

PMID- 27692828
TI  - Happy@feet application for the management of diabetic foot osteomyelitis.
AB  - OBJECTIVE: We aimed to develop and implement an application that could improve
      the management of patients presenting with diabetic foot osteomyelitis. PATIENTS
      AND METHODS: Physicians from the multidisciplinary diabetic foot infection team
      and a software engineer first assessed the needs required for the infection
      management and application. An experimental version was then designed and
      progressively improved. A final version was implemented in clinical practice in
      2013 by the multidisciplinary diabetic foot infection team of our university
      hospital. RESULTS: The application, known as Happy@feet, helps gather and allows
      access to all required data for patient management, dispenses prescriptions
      (antibiotics, nursing care, blood tests), and helps follow the evolution of the
      wound. At the end of the consultation, a customizable letter is generated and may
      be directly sent to the persons concerned. This application also facilitates
      clinical and economic research. In 2014, Happy@feet was used to follow 83
      patients during 271 consultations, 88 of which were day care hospitalizations.
      CONCLUSION: The Happy@feet application is useful to manage these complex
      patients. Once the learning period is over, the time required for data collection
      is compensated by the rapid dispense of prescriptions and letters. Happy@feet can
      be used for research projects and will be used in a remote patient management
      project.

PMID- 27692829
TI  - Invasive toxocariasis with hepatic lesions.

PMID- 27692830
TI  - [Histoplasma capsulatum disseminated necrotizing granulomatosis].

PMID- 27692831
TI  - 7-Chloro-4-aminoquinoline gamma-hydroxy-gamma-lactam derived-tetramates as a new
      family of antimalarial compounds.
AB  - In this Letter we report on an efficient and short 2-3 steps synthesis of gamma
      hydroxy-gamma-lactam derived-tetramates bearing a 7-chloro-4-aminoquinoline
      skeleton and their evaluation as potent antimalarials. These molecules were
      obtained through ring opening-ring closure (RORC) process of gamma-ylidene
      tetronate derivatives in the presence of 7-chloro-4-aminoquinoline-derived
      amines. In vitro antimalarial activity of these new gamma-lactams was evaluated
      against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and
      they were found to be active in the range of 14-827nM with generally good
      resistance index. A preliminary SAR study is also presented to explain these
      results. Finally, the most active compounds did not show in vitro cytotoxicity
      when tested against Human Umbilical Vein Endothelial Cells (HUVEC) up to
      concentration of 50MUM and they were stable at pH 7.4 for at least 48h.

PMID- 27692832
TI  - Synthesis and evaluation of a 2-benzothiazolylphenylmethyl ether class of
      histamine H4 receptor antagonists.
AB  - Synthesis and biological evaluation of a new class of histamine H4 receptor
      ligands, distinct from the previously reported chemotypes, are described. A
      virtual screening of our corporate compound collection identified a hit with an
      undesired dual H3R/H4R activity. Chemical exploration led to the discovery of a
      more potent and selective 2-benzothiazolylphenylmethyl ether lead compound.

PMID- 27692833
TI  - Risk of lymph node metastases in pathological gleason score<=6 prostate
      adenocarcinoma: Analysis of institutional and population-based databases.
AB  - INTRODUCTION: Several institutional studies have suggested that pathological
      Gleason score<=6 prostate cancer has little or no capacity for metastasis.
      MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results
      database (SEER, 2004-2011, n = 19,594) and the National Cancer Database (NCDB,
      2004-2013, n = 57,540), we identified patients with pathological Gleason score<=6
      prostate cancer following radical prostatectomy and lymph node dissection. At the
      University of Chicago Medicine (UCM, 2003-2014), we considered men with Gleason
      score<=6 prostate cancer who did (n = 267) and did not receive (n = 770) a lymph
      node dissection at the time of radical prostatectomy. Temporal trends in lymph
      node dissection and lymph node metastases were determined, and multivariable
      logistic regressions were used to analyze factors associated with lymph node
      metastases. In the UCM cohort, we also evaluated secondary endpoints, including
      biochemical recurrence (BCR), metastatic disease on follow-up imaging, and
      response to salvage radiation therapy. RESULTS: The incidence of lymph node
      dissection at the time of radical prostatectomy decreased from 60% to 37% in SEER
      (2004-2011) and from 62% to 45% in NCDB (2004-2013). Positive lymph node
      metastases were found in 0.2% of SEER and 0.18% of NCDB patients who received a
      lymph node dissection. Elevated PSA, higher clinical stage, and African American
      race were associated with lymph node positivity in one or both of these databases
      (P<0.05). Among UCM patients who received a lymph node dissection, no lymph node
      metastases were found, though a BCR occurred in 3 cases (1%). All 3 men responded
      favorably to salvage therapy, suggestive of local recurrence. A total of 21
      patients (3%) from UCM who did not receive a lymph node dissection had a BCR and
      underwent salvage radiation therapy. Of these, 4 patients had persistently
      detectable PSA levels without evidence of local or distant disease at median
      follow-up of 65 months (range: 29-79) following salvage therapy. Surgical
      specimens were available for contemporary pathologic review in 3 of these cases,
      and all were upgraded to Gleason 7 disease. CONCLUSIONS: Our population-based and
      institutional analyses suggest metastases in cases of Gleason score<=6 prostate
      cancer to be extremely rare.

PMID- 27692834
TI  - Localized chromophobe carcinomas treated by nephron-sparing surgery have
      excellent oncologic outcomes.
AB  - OBJECTIVE: To evaluate the oncologic outcomes of nephron-sparing surgery (NSS)
      for localized chromophobe renal cell carcinoma (cRCC). MATERIAL AND METHODS: We
      performed a multicenter international study involving the French Network for
      Research on Kidney Cancer (UroCCR) and 5 international teams. Data from 808
      patients treated with NSS between 2004 and 2014 for non-clear cell RCCs were
      analyzed. RESULTS: We included 234 patients with cRCC. There were 123 (52.6%)
      females. Median age was 61 (23-88) years. Median tumor size was 3 (1-11)cm. A
      positive surgical margin was identified in 14 specimens (6%). Pathologic stages
      were T1, T2, and T3a in 202 (86.3%), 9 (3.8%), and 23 (9.8%) cases, respectively.
      After a mean follow-up of 46.6 +/- 36 months, 2 (0.8%) patients experienced a
      local recurrence. No patient had metastatic progression, and no patient died from
      cancer. Three-years estimated cancer-free survival and cancer-specific survival
      were 99.1% and 100%, respectively. CONCLUSION: Oncological results of NSS for
      localized cRCC are excellent. In this series, only 2 patients had a local
      recurrence, and no patient had metastatic progression or died from cancer.

PMID- 27692836
TI  - Predictive models and risk of biopsy progression in active surveillance patients.
AB  - OBJECTIVE: To analyze the performance of different radical prostatectomy-based
      prognostic tools in predicting the biopsy progression in our active surveillance
      cohort. MATERIALS AND METHODS: We analyzed 326 patients with biopsy Gleason
      grade<=6,<=2 positive biopsy cores,<=20% tumor present in any core, prostate
      specific antigen<15ng/dl, and clinical stages T1-T2a all of whom had at least
      single surveillance biopsy. Probabilities of pathologically relatively aggressive
      disease were estimated using Partin and Dinh risk tables and Kattan, Truong, and
      Kulkarni nomograms for each individual patient. Using these predictions,
      performance of these tools was quantified regarding discrimination,
      stratification at different cut-points, calibration, and the clinical net
      benefit. RESULTS: Predictions of Partin and Dinh tables were not associated with
      the biopsy progression. The predictive value of Kattan and Truong nomograms was
      higher when compared with the other tools, although it was significant only on
      the first and second surveillance biopsies. Both nomograms were able to identify
      low- and high-risk subgroups within the cohort. Kattan nomogram demonstrated
      better correlation with the observed rate of progression over the first 3
      biopsies and higher clinical net benefit. CONCLUSION: Kattan and Truong nomograms
      demonstrated the best performance in predicting biopsy progression, although
      their value was largely limited to the first 2 surveillance biopsies. Both tools
      were able to stratify patients into subgroups with different risks of
      progression. These nomograms have important differences, which suggest that a
      more effective predictive model combining the strong sides of both tools and
      possibly some other variables could be developed.

PMID- 27692837
TI  - Central zone lesions on magnetic resonance imaging: Should we be concerned?
AB  - INTRODUCTION AND OBJECTIVE: The Prostate Imaging Reporting and Data System (PI
      RADS) score was developed to evaluate lesions in the peripheral and transition
      zone on multiparametric magnetic resonance imaging (mpMRI) of the prostate. We
      aim to determine if the PI-RADS scoring system can be used to evaluate central
      zone lesions on mpMRI. MATERIALS AND METHODS: A retrospective review of 73
      patients who underwent mpMRI/ultrasound (US) fusion-guided biopsy of 143
      suspicious lesions between February 2014 and October 2015 was performed. All
      patients underwent a 3T mpMRI. Indications for mpMRI included an abnormal digital
      rectal examination, PSA velocity >0.75ng/dl/y, and patients on active
      surveillance. The mpMRI sequence involved T2-weighted imaging, diffusion-weighted
      imaging, and dynamic contrast enhancement. Using 3-dimensional model software
      (Invivo Corporation, Gainesville, FL, USA), a minimum of 3 magnetic resonance
      imaging (MRI)/US fusion-guided biopsy samples were taken from each prostate
      lesion seen on mpMRI irrespective of PI-RADS score, using local anesthesia in an
      outpatient clinic setting. RESULTS: A total of 73 patients underwent MRI/US
      fusion-guided biopsy of 85 peripheral zone lesions, 31 transitional zone lesions,
      and 27 central zone lesions. Only 2 (7%) of central zone lesions were positive
      for prostate cancer. Both patients had lesions which were graded as PI-RADS 3.
      Both the patients had multifocal lesions that encompassed>=50% of the central and
      transition zones on the sagittal view MRI images. Both patients previously had
      transrectal US-guided biopsy of the prostate which was negative for cancer. Both
      patients underwent a robotic-assisted laparoscopic prostatectomy, each revealing
      high-grade cancer. CONCLUSIONS: Lesions involving only the central gland/zone
      seen on MRI are less concerning for malignancy and should not be given equal
      weight as peripheral zone lesions. In this series, no lesions involving solely
      the central gland/zone, regardless of PI-RADS score, was positive for malignancy
      on MRI/US fusion-guided biopsy. Consideration of a modified PI-RADS scoring
      system should be given to help identify central zone lesions with malignant
      potential.

PMID- 27692835
TI  - Hepatoma-derived growth factor: A survival-related protein in prostate
      oncogenesis and a potential target for vitamin K2.
AB  - Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor, which
      has previously been shown to be expressed in a variety of cancers. HDGF
      overexpression has also previously been correlated with a poor prognosis in
      several cancers. The significance of HDGF in prostate cancer, however, has not
      been investigated. Here, we show that HDGF is overexpressed in both androgen
      sensitive LNCaP cells and androgen-insensitive DU145, 22RV1, and PC-3 cells.
      Forced overexpression enhanced cell viability of RWPE-1 cells, whereas HDGF
      knockdown reduced cell proliferation in human prostate cancer cells. We also show
      that HDGF may serve as a survival-related protein as ectopic overexpression of
      HDGF in RWPE cells up-regulated the expression of antiapoptosis proteins cyclin E
      and BCL-2, whereas simultaneously down-regulating proapoptotic protein BAX.
      Western blot analysis also showed that HDGF overexpression modulated the activity
      of phospho-AKT as well as NF-kB, and these results correlated with in vitro
      migration and invasion assays. We next assessed the therapeutic potential of HDGF
      inhibition with a HDGF monoclonal antibody and vitamin k2, showing reduced cell
      proliferation as well as inhibition of NF-kB expression in HDGF overexpressed
      RWPE cells treated with a HDGF monoclonal antibody and vitamin K2. Collectively,
      our results suggest that HDGF is a relevant protein in prostate oncogenesis and
      may serve as a potential therapeutic target in prostate cancer.

PMID- 27692838
TI  - Pulmonary Contusion and Traumatic Pneumatoceles in a Platform Diver with
      Hemoptysis.
AB  - BACKGROUND: Injuries in divers resulting purely from impact with the water are
      uncommon in the published literature. We present a case report of pulmonary
      contusion in a young diver. CASE REPORT: A young, healthy competitive platform
      diver landed flat on his back in the water from a dive of 10 meters. He
      complained of upper back pain and had an episode of hemoptysis after the dive. He
      was initially observed for 15 hours postinjury, and was discharged when three
      chest radiographs (CXRs) taken at 1, 7, and 11 hours postinjury did not show
      significant abnormalities. Thirty-six hours postinjury, the patient experienced
      repeat hemoptysis and returned to the emergency department, where a fourth CXR
      performed 43 hours postinjury was normal. A computed tomography (CT) scan
      revealed pulmonary contusion and traumatic subpleural pneumatoceles. The patient
      was admitted to the cardiothoracic ward for observation. He recovered well with
      conservative treatment and was discharged on the fifth day after injury with
      clearance for air travel. In this patient with a high-energy mechanism of rapid
      deceleration and hemoptysis at the scene, there may be grounds for performing a
      CT scan of the thorax at the time of the first presentation, although the CT
      findings did not change conservative management of this patient. WHY SHOULD AN
      EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should recognize that
      a dive into water may generate sufficient impact to produce a pulmonary
      contusion. If the patient is clinically well and the CXR results are normal, the
      decision to initiate a CT scan and subsequent disposition may be based on
      clinical judgement and institutional practice.

PMID- 27692839
TI  - Survey and Chart Review to Estimate Medicare Cost Savings for Home Health as an
      Alternative to Hospital Admission Following Emergency Department Treatment.
AB  - BACKGROUND: Almost 70% of hospital admissions for Medicare beneficiaries
      originate in the emergency department (ED). Research suggests that some of these
      patients' needs may be better met through home-based care options after
      evaluation and treatment in the ED. OBJECTIVE: We sought to estimate Medicare
      cost savings resulting from using the Home Health benefit to provide treatment,
      when appropriate, as an alternative to inpatient admission from the ED. METHODS:
      This is a prospective study of patients admitted from the ED. A survey tool was
      used to query both emergency physicians (EPs) and patient medical record data to
      identify potential candidates and treatments for home-based care alternatives.
      Patient preferences were also surveyed. Cost savings were estimated by developing
      a model of Medicare Home Health to serve as a counterpart to the actual hospital
      based care. RESULTS: EPs identified 40% of the admitted patients included in the
      study as candidates for home-based care. The top three major diagnostic
      categories included diseases and disorders of the respiratory system, digestive
      system, and skin. Services included intravenous hydration, intravenous
      antibiotics, and laboratory testing. The average estimated cost savings between
      the Medicare inpatient reimbursement and the Home Health counterpart was
      approximately $4000. Of the candidate patients surveyed, 79% indicated a
      preference for home-based care after treatment in the ED. CONCLUSIONS: Some
      Medicare beneficiaries could be referred to Home Health from the ED with a
      concomitant reduction in Medicare expenditures. Additional studies are needed to
      compare outcomes, develop the logistical pathways, and analyze infrastructure
      costs and incentives to enable Medicare Home Health options from the ED.

PMID- 27692840
TI  - Clinical Mimics: An Emergency Medicine-Focused Review of Sepsis Mimics.
AB  - BACKGROUND: Sepsis is a common clinical condition, and mortality and morbidity
      may be severe. The current definition of sepsis involves systemic inflammatory
      response syndrome (SIRS) criteria, which is met by many conditions. OBJECTIVE:
      This review evaluates the SIRS continuum, signs and symptoms of sepsis, mimics of
      sepsis, and an approach to management for sepsis mimics. DISCUSSION: The current
      emergency medicine definition of sepsis includes SIRS, a definition that may be
      met by many conditions. Because of common pathophysiologic responses, these
      diseases present in a similar manner. These conditions include anaphylaxis,
      gastrointestinal emergency, pulmonary disease, metabolic abnormality, toxin
      ingestion/withdrawal, vasculitis, and spinal injury. Many of these conditions can
      be deadly if they are not diagnosed and managed. However, differentiating between
      sepsis and mimics can be difficult in the emergency setting. Laboratory
      abnormalities in isolation do not provide a definitive diagnosis. However, a
      combination of history, physical examination, and adjunctive studies may assist
      providers. For the patient in extremis, resuscitation must take precedence while
      attempts to differentiate sepsis from mimics are underway. CONCLUSIONS: SIRS and
      sepsis exist along a continuum, with many other conditions overlapping because of
      a common physiologic response. A combination of factors will assist providers in
      differentiating sepsis from mimics rather than using diagnostic studies in
      isolation. Resuscitation should be initiated while attempting to differentiate
      sepsis from its mimics.

PMID- 27692841
TI  - Use of High-Dose Phenylephrine in the Treatment of Ischemic Priapism: Five-Year
      Experience at a Single Institution.
AB  - INTRODUCTION: Ischemic priapism is an uncommon urologic emergency characterized
      by a compartment syndrome-like ischemic insult to the corpora cavernosa of the
      penis. The goal of treatment in ischemic priapism is rapid detumescence to
      prevent long-term erectile dysfunction. Non-surgical treatment options include
      aspiration, irrigation, and intracavernous injections of sympathomimetic agents.
      At our institution, phenylephrine is used in the treatment of ischemic priapism
      at concentrations and doses that are higher than those recommended in established
      guidelines. AIM: To characterize our experience with high-concentration
      intracavernous phenylephrine in the treatment of ischemic priapism at an urban
      tertiary care center. METHODS: A retrospective chart review identified 58 unique
      patients presenting to the emergency department on 136 occasions and receiving
      the diagnosis of ischemic priapism by urologic physicians. Patients' charts were
      reviewed to record the dosing of phenylephrine and the outcomes and circumstances
      of the presentation. MAIN OUTCOME MEASURES: Success rates of different treatment
      strategies for different circumstances of presentation. RESULTS: Successful
      detumescence was achieved with non-surgical management in 86% of unique patients
      and the overall resolution rate when including repeat visits was 94%. All
      patients presenting within less than 36 hours of priapism were successfully
      treated with non-surgical management. There were no reported complications or
      associated symptoms related to the use of intracavernous phenylephrine during the
      5-year period. CONCLUSION: The use of high concentration and dosing of
      intracavernous phenylephrine demonstrates a high success rate in the treatment of
      ischemic priapism. Future prospective studies are needed to further characterize
      appropriate phenylephrine dosing for its efficacy and safety.

PMID- 27692842
TI  - TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index
      in Postmenopausal Women With Vulvar and Vaginal Atrophy: The REJOICE Trial.
AB  - INTRODUCTION: TX-004HR is an investigational, applicator-free, vaginal soft gel
      capsule containing low-dose solubilized 17beta-estradiol. The phase 3,
      randomized, double-blinded, placebo-controlled, multicenter REJOICE trial has
      shown TX-004HR to be safe and effective for the treatment of moderate to severe
      dyspareunia in postmenopausal women with vulvar and vaginal atrophy (VVA). AIM:
      To evaluate the effect of TX-004HR on female sexual dysfunction in postmenopausal
      women with VVA. METHODS: The REJOICE study compared the effects of 12-week
      treatment with TX-004HR (4, 10, or 25 MUg) with placebo in postmenopausal women
      (40-75 years old) with VVA and a most bothersome symptom of moderate to severe
      dyspareunia. Changes in the percentage of superficial and parabasal cells,
      vaginal pH, and dyspareunia were measured as co-primary end points. Female sexual
      dysfunction was evaluated as a secondary end point using the Female Sexual
      Function Index (FSFI) patient self-report inventory. MAIN OUTCOME MEASURES:
      Changes from baseline to week 12 in total and individual domain FSFI scores for
      each TX-004HR dose were compared with those for placebo. RESULTS: All three TX
      004HR doses increased the baseline total FSFI score after 12 weeks, with 10 MUg
      (P < .05) and 25 MUg (P = .0019) having a significantly greater effect than
      placebo. A similar trend was observed for the individual FSFI domains, with 10
      and 25 MUg significantly improving baselines scores for pain and lubrication at
      12 weeks (P <= .015 for all vs placebo). Changes from baseline to week 12 in
      arousal (P = .0085) and satisfaction (P = .0073) were significantly greater for
      TX-004HR 25 MUg vs placebo. All three TX-004HR doses were comparable to placebo
      in their effect on desire and orgasm. CONCLUSION: TX-004HR improved FSFI scores
      in a dose-dependent manner. The observed improvements in sexual function suggest
      that TX-004HR is a promising treatment option for postmenopausal VVA with a
      potential added beneficial effect on female sexual dysfunction.

PMID- 27692843
TI  - Role of Body Esteem in the Sexual Excitation and Inhibition Responses of Women
      With and Without a History of Childhood Sexual Abuse.
AB  - INTRODUCTION: Women's sexuality is influenced by their perceptions of their
      bodies. Negative body appraisals have been implicated in the development and
      maintenance of sexual concerns in women with a history of childhood sexual abuse
      (CSA). The sexuality of these women is often expressed in extremes of approach
      and avoidant sexual tendencies, which have been related to the sexual inhibition
      and sexual excitation pathways of the dual control model. AIM: To test the
      influence of body esteem on the sexual excitation and inhibition responses of
      women with and without a history of CSA. METHODS: One hundred thirty-nine women
      with CSA and 83 non-abused women reported on their abuse history, depressive
      symptomology, sexual response, and affective appraisals of their body. MAIN
      OUTCOME MEASURES: Validated self-report measurements of sexual excitation and
      inhibition responses (Sexual Excitation/Sexual Inhibition Inventory for Women)
      and body esteem (Body Esteem Scale) were administered. RESULTS: Body esteem was
      significantly associated with sexual inhibition responses of women regardless of
      CSA history status but was significantly related only to the sexual excitation
      responses of women with a CSA history. Perceived sexual attractiveness was a
      unique predictor of sexual excitation in women with a history of CSA. CONCLUSION:
      Women with a history of CSA have lower body esteem than non-abused women,
      particularly in self-perceived sexual attractiveness, and these perceptions
      appear to influence their sexual responses by acting on the sexual excitation and
      inhibition response pathways.

PMID- 27692844
TI  - Cardiometabolic Risk and Female Sexuality: Focus on Clitoral Vascular Resistance.
AB  - INTRODUCTION: The relation between sexual and cardiovascular health in women is
      not well defined. Clitoral color Doppler ultrasound (CDU) with assessment of the
      pulsatility index (PI), reflecting resistance to blood flow, has been proposed as
      an objective measurement of sexual functioning. AIM: To investigate associations
      between clitoral PI and cardiometabolic risk factors, sexual and intrapsychic
      parameters, and self-perception of body image. METHODS: Seventy-one adult
      heterosexual women in a stable relationship attending our clinic for sexual
      dysfunction were consecutively recruited. MAIN OUTCOME MEASURES: Patients
      underwent physical, laboratory, and clitoral color Doppler ultrasound
      examinations and completed the Female Sexual Function Index, the Middlesex
      Hospital Questionnaire, and the Body Uneasiness Test (BUT). RESULTS: Clitoral PI
      was positively correlated with body mass index (r = 0.441, P < .0001), waist
      circumference (r = 0.474, P < .0001), glycemia (r = 0.300, P = .029), insulin (r
      = 0.628, P = .002), homeostatic model assessment index (r = 0.605, P = .005),
      triglycerides (r = 0.340, P = .011), total cholesterol (r = 0.346, P = .010), and
      low-density lipoprotein cholesterol (r = 0.334, P = .016). All relations, with
      the exception of glycemia, retained statistical significance after adjusting for
      age, smoking habit, and years since menopause (P < .0001 for body mass index,
      waist circumference, and triglycerides; P < .05 for all other associations).
      Analysis of covariance, after adjusting for confounders, showed that women with
      obesity or metabolic syndrome (MetS) showed significantly higher PI values
      (obesity: F = 17.79, P = .001; MetS: F = 7.37, P = .019). In particular, a
      stepwise increase of PI was found as a function of increasing MetS components
      (beta = 0.434, P = .007). Clitoral PI was negatively associated with Female
      Sexual Function Index arousal (beta = -0.321, P = .014) and satisfaction (beta = 
      0.289, P = .026) scores and positively associated with Middlesex Hospital
      Questionnaire somatized anxiety symptoms, even after adjusting for age, smoking
      habit, years since menopause, and current use of psychiatric medication (beta =
      0.354, P = .011). A positive association also was observed between PI and the BUT
      positive symptom distress index (beta = 0.322, P = .039) and BUT for dislike of
      the womb, genitals, and breast (beta = 0.538, P < .0001; beta = 0.642, P < .0001;
      beta = 0.549, P < .0001, respectively). After introducing waist circumference as
      another covariate, the associations between clitoral PI and the BUT positive
      symptom distress index and BUT dislike of the womb, genitals, and breast retained
      statistical significance (P = .038 for positive symptom distress index; P < .0001
      for dislike of womb, genitals, and breast). CONCLUSION: Clitoral vascular
      resistance is positively associated with MetS (in particular insulin resistance),
      decreased sexual arousal, body image concerns, and increased somatized anxiety
      symptoms. Further studies are needed to establish whether treatment of metabolic
      abnormalities might improve clitoral color Doppler ultrasound indices and sexual
      outcomes.

PMID- 27692845
TI  - Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire.
AB  - INTRODUCTION: The Hypogonadism Impact of Symptoms Questionnaire (HIS-Q) is a
      patient-reported outcome measurement designed to comprehensively evaluate the
      symptoms of hypogonadism and to detect changes in these symptoms in response to
      treatment. AIM: To conduct item analysis and reduction, evaluate the psychometric
      properties of the HIS-Q, and provide guidance on interpreting the instrument
      score. METHODS: A 12-week observational, longitudinal study of hypogonadal men
      was conducted. Participants completed the HIS-Q every 2 weeks. Blood samples were
      collected to evaluate testosterone levels. Participants also completed the Aging
      Male's Symptoms Scale, the International Index of Erectile Function, the Short
      Form-12 Health Survey, and the Patient-Reported Outcomes Measurement Information
      System Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and
      Applied Cognition Scales (at baseline and weeks 6 and 12). Clinicians completed
      the Clinical Global Impression of Severity and Change measurements and a clinical
      form. MAIN OUTCOME MEASURES: Individual item performance was evaluated using
      descriptive statistics and Rasch analyses. Reliability (internal consistency and
      test-retest), validity (concurrent and know groups), and responsiveness were
      assessed. RESULTS: In total, 177 men participated in the study (mean age = 54.1
      years, range = 23-83). The original 53-item draft HIS-Q was reduced to 28 items;
      the final instrument included five domains (sexual, energy, sleep, cognition, and
      mood) with two sexual subdomains (libido and sexual function). For all domains,
      test-retest reliability was acceptable (intraclass correlation coefficients >
      0.70), construct validity was good (|r > 0.30| for all comparisons). Known-groups
      validity was demonstrated for all HIS-Q domain scores, subdomain scores, and the
      total score as measured by the Clinical Global Impression of Severity, and total
      testosterone level at baseline (P < .05 for all comparisons). All domains and
      subdomains were responsive to change based on patient-rated anchor questions (P <
      .05 for all comparisons). CONCLUSION: The final 28-item HIS-Q is reliable, valid,
      and responsive. The HIS-Q is suitable for inclusion in future clinical trials to
      help characterize the effects of testosterone replacement therapy.

PMID- 27692847
TI  - Molecular complexity of taxane-induced cytotoxicity in prostate cancer cells.
AB  - BACKGROUND: Taxanes are routinely used to treat men with advanced prostate
      cancer, yet their molecular mode of action is poorly characterized. Taxanes
      stabilize microtubules and may hence interfere with a plethora of cellular
      processes, most notably mitosis. However, prostate cancer is typically a slowly
      growing tumor suggesting that additional processes play a role in the response to
      taxanes. METHODS: Here, we analyzed the potential effect of taxanes on
      microtubuli-dependent intracellular transport and signaling processes,
      specifically, nuclear translocation of the androgen receptor and modulation of
      the RAS-RAF-MEK-ERK signaling cascade. RESULTS: We show that the androgen-driven
      nuclear translocation of the androgen receptor remains virtually undisturbed by
      docetaxel in prostate cancer cells. However, we found a striking down-regulation
      of activated ERK1/2 together with enhanced cytotoxicity in both docetaxel or
      cabazitaxel-treated cells that was comparable to direct MEK kinase inhibition.
      Remarkably, MEK inhibition alone was less effective in inducing cytotoxicity than
      taxanes indicating that a down-regulation of activated ERK1/2 may be necessary
      but is not sufficient for taxane-induced antitumoral effects. In line with this
      notion, we show in a xenograft mouse model that prostate cancer cells that are
      resistant to docetaxel overexpress activated ERK1/2. Taken together, our findings
      underscore that the modulation of ERK1/2 activation, in concert with other
      mechanisms, plays an important role in taxane-induced antineoplastic effects on
      prostate cancer cells. CONCLUSIONS: These results suggest at least partially
      nonoverlapping effects of docetaxel and androgen deprivation therapy and hence
      help to understand recent clinical findings. A further elucidation of the mode of
      action of docetaxel would have important implications to optimize current
      treatment strategies and biomarker development for men with metastatic prostate
      cancer.

PMID- 27692846
TI  - The structural connectivity of higher order association cortices reflects human
      functional brain networks.
AB  - Human higher cognition arises from the main tertiary association cortices
      including the frontal, temporal and parietal lobes. Many studies have suggested
      that cortical functions must be shaped or emerge from the pattern of underlying
      physical (white matter) connectivity. Despite the importance of this hypothesis,
      there has not been a large-scale analysis of the white-matter connectivity within
      and between these associative cortices. Thus, we explored the pattern of intra-
      and inter-lobe white matter connectivity between multiple areas defined in each
      lobe. We defined 43 regions of interest on the lateral associative cortex
      cytoarchitectonically (6 regions of interest - ROIs in the frontal lobe and 17
      ROIs in the parietal lobe) and anatomically (20 ROIs in the temporal lobe) on
      individuals' native space. The results demonstrated that intra-region
      connectivity for all 3 lobes was dense and graded generally. In contrary, the
      inter-lobe connectivity was relatively discrete and regionally specific such that
      only small sub-regions exhibited long-range connections to another lobe. The long
      range connectivity was mediated by 6 major associative white matter tracts,
      consistent with the notion that these higher cognitive functions arises from
      brain-wide distributed connectivity. Using graph-theory network analysis we
      revealed five physically-connected sub-networks, which correspond directly to
      five known functional networks. This study provides strong and direct evidence
      that core functional brain networks mirror the brain's structural connectivity.

PMID- 27692848
TI  - Changes in expressions of ADAM9, 10, and 17 as well as alpha-secretase activity
      in renal cell carcinoma.
AB  - BACKGROUND: ADAM9, 10, and 17 are a class of disintegrins and metallproteinases
      with alpha-secretase activity. There are conflicting results regarding the
      role(s) of ADAM9, 10, and 17 in carcinogenesis, and only a few studies have
      examined their levels and cellular localization in renal cell carcinoma (RCC).
      Studies examining changes in alpha-secretase activity in RCC compared to
      enzymatic activity of the uninvolved kidney are lacking. METHOD: A cross
      sectional study was conducted in 56 patients undergoing radical nephrectomy after
      the diagnosis of RCC. alpha-Secretase activity was determined using flourogenic
      substrate in freshly frozen tumor tissues as well as similarly treated tissues
      from the neighboring kidney. Immunohistochemical analyses of ADAM9, 10, and 17
      were also performed. RESULTS: alpha-Secretase activity decreased markedly in all
      types of RCC as compared to neighboring uninvolved kidney tissue having 5 to 10
      times higher levels of alpha-secretase activity. Although type-dependent
      variations were observed, tumoral expressions of ADAMs, except for ADAM17, were
      lower in the tumors compared to that of neighboring tissues, but the changes in
      alpha-secretase activity were greater. In RCC tissue, ADAM9 expressions were
      localized in nuclear and cytoplasmic compartments, whereas ADAM10 and 17 were
      present predominately in the cytoplasm potentially explaining the markedly
      decreased enzyme activity. Membranous localization of ADAMs was noted in
      uninvolved kidney tissue. CONCLUSIONS: The loss of alpha-secretase activity
      observed here in conjunction with previous findings argue against tumorigenic
      effects of ADAM9, 10, and 17 supporting that increased nuclear and cytoplasmic
      expression may be an attempt to compensate for loss of function.

PMID- 27692850
TI  - HbA1c as a predictor of diabetes after gestational diabetes mellitus.
AB  - AIM: We wanted to investigate third-trimester HbA1c as a predictor of diabetes
      after gestational diabetes mellitus (GDM). METHODS: Women with GDM were followed
      up prospectively for five years from pregnancy to detect the development of
      diabetes. The ability of HbA1c to predict diabetes was evaluated with receiver
      operating characteristic (ROC) curves and logistic regression analysis. RESULTS:
      By five years, 73 of 196 women had been diagnosed with diabetes. An optimal cut
      off point for HbA1c of 36mmol/mol (5.4%) could predict diabetes with 45%
      sensitivity and 92% specificity. For HbA1c >=39mmol/mol (>=5.7%), sensitivity,
      specificity, and positive predictive value were 30%, 97%, and 91%, respectively.
      In logistic regression analysis, adjusting for the diagnostic glucose
      concentration during pregnancy, HbA1c levels in the upper quartile (>=36mmol/mol)
      were associated with a 5.5-fold increased risk of diabetes. CONCLUSION: Third
      trimester HbA1c levels in the pre-diabetes range revealed women with post-partum
      diabetes with high specificity and high positive predictive value. HbA1c testing
      could be used as a strategy to select high-risk women for lifestyle interventions
      aimed at prevention of diabetes starting during pregnancy. The results should
      encourage further validation in other populations using new diagnostic criteria
      for GDM.

PMID- 27692851
TI  - Bilateral mammoplasty for cancer: Surgical, oncological and patient-reported
      outcomes.
AB  - INTRODUCTION: Bilateral mammoplasty (BM) can optimise oncological safety and
      aesthetic outcomes in women with large or ptotic breasts whose tumour to breast
      volume ratio or tumour location pose a challenge to standard breast-conserving
      therapy (BCT) and for whom mastectomy (with or without reconstruction) may be the
      only alternative. METHODS: We undertook a comprehensive analysis of surgical
      outcomes (complications according to the Clavien Dindo classification), acute
      radiation morbidity (Radiation Therapy Oncology Group classification),
      oncological outcomes, and patient satisfaction (BREAST-Q questionnaire) in women
      who underwent BM for breast cancer (BC) from June 2009-November 2014. RESULTS:
      168 women were included. Median age was 55 years (range:33-84) and median tumour
      size at imaging 35 mm (range:0-170). Median specimen weight was 242 g (range 39
      1824). The wise pattern technique was used in 87.5% of procedures. At least one
      complication occurred in 68 (40.5%) women, mostly Clavien Dindo grade 1. Grade 3
      complications were infrequent (8.9%) but occurred mainly on the therapeutic
      mammoplasty (TM) side (p < 0.05). Complications were associated with higher BMI,
      specimen weight and longer time to radiotherapy (p < 0.05). Median follow-up was
      37 months (range: 13-77). Local recurrence occurred in 3 (1.8%), distant
      metastases in 5 (3.0%), and 10 (6.0%) women have died. The median score for
      'satisfaction with breasts' was 77 (range: 0-100). CONCLUSIONS: This study
      provides concurrent data on surgical, oncological and patient-reported outcomes.
      It offers evidence that BM is an effective treatment for breast cancer in large-
      or ptotic-breasted women.

PMID- 27692852
TI  - Pragmatic Language Interpretation as Probabilistic Inference.
AB  - Understanding language requires more than the use of fixed conventions and more
      than decoding combinatorial structure. Instead, comprehenders make exquisitely
      sensitive inferences about what utterances mean given their knowledge of the
      speaker, language, and context. Building on developments in game theory and
      probabilistic modeling, we describe the rational speech act (RSA) framework for
      pragmatic reasoning. RSA models provide a principled way to formalize inferences
      about meaning in context; they have been used to make successful quantitative
      predictions about human behavior in a variety of different tasks and situations,
      and they explain why complex phenomena, such as hyperbole and vagueness, occur.
      More generally, they provide a computational framework for integrating linguistic
      structure, world knowledge, and context in pragmatic language understanding.

PMID- 27692849
TI  - Calcium at the Center of Cell Signaling: Interplay between Endoplasmic Reticulum,
      Mitochondria, and Lysosomes.
AB  - In recent years, rapid discoveries have been made relating to Ca2+ handling at
      specific organelles that have important implications for whole-cell Ca2+
      homeostasis. In particular, the structures of the endoplasmic reticulum (ER) Ca2+
      channels revealed by electron cryomicroscopy (cryo-EM), continuous updates on the
      structure, regulation, and role of the mitochondrial calcium uniporter (MCU)
      complex, and the analysis of lysosomal Ca2+ signaling are milestones on the route
      towards a deeper comprehension of the complexity of global Ca2+ signaling. In
      this review we summarize recent discoveries on the regulation of interorganellar
      Ca2+ homeostasis and its role in pathophysiology.

PMID- 27692853
TI  - 1,10-Phenanthroline and its derivatives are novel hatching stimulants for soybean
      cyst nematodes.
AB  - Soybean cyst nematode (SCN), Heterodera glycines Ichinohe, is a plant-parasitic
      nematode and one of the most serious soybean pests. Herein, we present the
      heterocyclic compound 1,10-phenanthroline (Phen) and its derivatives as novel
      hatching stimulants for SCN. Phen treatment promoted hatching of second-stage
      juveniles of SCNs in a concentration-dependent manner. In addition, the hatching
      of SCNs following treatment with Phen occurred more rapidly than that following
      treatment with the known hatching stimulant, glycinoeclepin A (GEA). Furthermore,
      the co-application of Phen and GEA enhanced SCN hatching rate compared with that
      of Phen or GEA alone. A structure-activity relationship study for Phen
      derivatives suggested that 2,2'-bipyridine is the essential structure of the SCN
      hatching stimulants. These results suggest that Phen and its derivatives activate
      different hatching pathways of SCNs from GEA.

PMID- 27692854
TI  - N-Arylsulfonyl-alpha-amino carboxamides are potent and selective inhibitors of
      the chemokine receptor CCR10 that show efficacy in the murine DNFB model of
      contact hypersensitivity.
AB  - Compound 1 ((4-amino-3,5-dichlorophenyl)-1-(4-methylpiperidin-1-yl)-4-(2
      nitroimidazol-1-yl)-1-oxobutane-2-sulfonamido) was discovered to be a 690nM
      antagonist of human CCR10 Ca2+ flux. Optimization delivered (2R)-4-(2-cyanopyrrol
      1-yl)-S-(1H-indol-4-yl)-1-(4-methylpiperidin-1-yl)-1-oxobutane-2-sulfonamido (eut
      22) that is 300 fold more potent a CCR10 antagonist than 1 and eliminates
      potential toxicity, mutagenicity, and drug-drug-interaction liabilities often
      associated with nitroaryls and anilines. eut-22 is highly selective over other
      GPCR's, including a number of other chemokine receptors. Finally, eut-22 is
      efficacious in the murine DNFB model of contact hypersensitivity. The efficacy of
      this compound provides further evidence for the role of CCR10 in dermatological
      inflammatory conditions.

PMID- 27692855
TI  - Systematic Review and Single-Center Experience for Endovascular Management of
      Visceral and Renal Artery Aneurysms.
AB  - PURPOSE: To report a systematic review of endovascular management of visceral and
      renal artery aneurysms (VRAA) and results at a tertiary referral center.
      MATERIALS AND METHODS: A literature review was performed via a comprehensive
      electronic search of PubMed, MEDLINE, EMBASE, and Cochrane databases, followed by
      retrospective analysis of all VRAAs treated at a tertiary referral center from
      January 1999 to December 2015. RESULTS: The systematic review included 22 studies
      published between 2005 and 2016 describing endovascular treatment of VRAA. In the
      systematic review cohort, 646 aneurysms (432 true, 151 false, 63 unclassified)
      were treated using endovascular methods with 93.2% technical success, 99.3%
      visceral preservation, 3.5% major complication (classified based on Society of
      Interventional Radiology criteria), 1.5% 30-day periprocedural mortality, and
      4.6% reintervention rates. In the local cohort, 19 aneurysms (12 true, 7 false)
      were treated with 100% technical success, 94.7% visceral preservation, and 10.5%
      major complication rates. There was no periprocedural mortality. Over mean follow
      up of 31.9 months (range, 2-170 months), there were 2 aneurysm reperfusions,
      which required no further treatment. Results incorporating data from the
      systematic review and local cohorts (665 aneurysms) showed 93.6% technical
      success, 99.1% visceral preservation, 3.7% major complication, 1.5%
      periprocedural mortality, and 4.4% reintervention rates. CONCLUSIONS:
      Endovascular treatment of VRAA is associated with excellent technical success and
      visceral preservation rates. Major complication and periprocedural mortality
      rates are comparatively low. A few VRAA (4.4%) required future reintervention
      suggesting that imaging follow-up is essential after initial treatment.

PMID- 27692856
TI  - The Effect of Bridging Locoregional Therapy and Sociodemographics on Survival in
      Hepatocellular Carcinoma Patients Undergoing Orthotopic Liver Transplantation: A
      United Network for Organ Sharing Population Study.
AB  - PURPOSE: To investigate socioeconomic and demographic factors associated with
      transplantation outcomes in patients with hepatocellular carcinoma (HCC) treated
      with bridging locoregional therapy (LRT) before orthotopic liver transplantation
      (OLT). MATERIALS AND METHODS: The United Network for Organ Sharing (UNOS)
      database was used to identify all patients in the United States with HCC who were
      listed for OLT between 2002 and 2013. Mean overall survival (OS) after OLT was
      stratified based on age, sex, ethnicity, transplant year, region, and insurance
      status. Kaplan-Meier estimation was used for survival analysis with log-rank test
      and Cox proportional hazards model to assess independent prognostic factors for
      OS. RESULTS: Of the 17,291 listed patients with HCC, 14,511 underwent OLT. Mean
      age was 57.4 years (76.8% male). Favorable sociodemographic factors were
      associated with increased rates of bridging LRT before OLT and longer wait time
      on the transplant list and were shown to be independent prognostic factors for
      prolonged OS after OLT using multivariate analysis. Favorable demographic factors
      included patient age < 60 years, donor age < 45 years, year of diagnosis between
      2008 and 2013, UNOS regions 4 and 5, Asian ethnicity, high functional status,
      postgraduate education, private payer insurance, and employment at the time of
      OLT. CONCLUSIONS: Patients with favorable sociodemographics had higher rates of
      LRT before OLT performed for HCC cure. These patients had longer transplant wait
      times and longer OS after OLT.

PMID- 27692858
TI  - On the stability of gold nanoparticles synthesized by laser ablation in liquids.
AB  - "Naked" gold nanoparticles (AuNPs), synthesized in the absence of any capping
      agents, prepared by pulsed laser ablation in liquid (PLAL) are stabilized by
      negative charges. Common explanations for this phenomenon involve the presence of
      gold oxides and/or the anion adsorption. We have found that AuNP ablated in
      solutions of acids with very different oxidation power, viz. HCl, H2SO4, HNO3
      share the same size and zeta-potential. Although, gold oxides have pKas~4, the
      zeta-potential of AuNPs ablated in solutions with pH?4 is always negative. These
      evidences suggest that the gold oxidation and anion adsorptions have only a minor
      role on building the negative surface potential and we hypothesize, for the first
      time, that excess electrons formed within the plasma phase could charge the
      metallic particles. In our model, a crucial point is that the colloidal size of
      the NP maintains the energy of the electrons small enough to preclude chemical
      reactions but with a surface potential yet large enough to stabilize the AuNPs
      with respect to aggregation. A confirmation of the hypothesis of "electron
      stabilized nanoparticles" is that either the addition of macroscopic metallic
      objects either the contact with a "grounded" copper wire induce the loss of
      charge and AuNPs aggregation.

PMID- 27692857
TI  - Insights into the central pathways involved in the emetic and behavioural
      responses to exendin-4 in the ferret.
AB  - BACKGROUND: GLP-1 receptor agonists are utilised for the treatment of Type-2
      diabetes but can be associated with undesirable effects of nausea and vomiting.
      OBJECTIVES: To investigate the role of GLP-1 receptors in mechanisms of emesis,
      behaviours indicative of nausea (BIN) and food intake in the ferret. RESULTS:
      Exendin-4 (10 and 30nmol, i.c.v.) induced emesis, inhibited food intake, and
      increased the frequency of BIN. Increases in c-Fos in the brainstem, midbrain and
      forebrain occurred in animals exhibiting emesis; no activation of the brainstem
      occurred in animals not vomiting. Exendin-4 (10nmol, i.c.v.) when preceded by
      i.c.v. saline (15MUl), was not emetic but induced BIN and inhibited food intake;
      exendin (9-39) (100nmol) reduced BIN only. c-Fos showed that consistent with the
      absence of emesis in saline/exendin-4 treated animals there was no increase in c
      Fos in the brainstem, but it increased in midbrain and forebrain nuclei.
      Excepting the amygdala, exendin (9-39) was without efffect on the increases in c
      Fos. Analysis of c-Fos data showed a positive linear relationship between
      midbrain and forebrain areas irrespective of the occurrence of emesis induced by
      exendin-4. In contrast, brainstem and midbrain c-Fos levels were positively
      correlated, but only in animals with emesis. CONCLUSIONS: The brainstem is
      critical for exendin-4-induced emesis but suppression of food intake and BIN
      involves more rostral brain sites. Exendin-4-induced BIN and c-Fos activation of
      the amygdala are sensitive to exendin (9-39), whereas the suppression of food
      intake is not implicating separate control mechanisms for emesis and BIN.

PMID- 27692859
TI  - Unusually High Calcaneal Speed of Sound Measurements in Children with Small Foot
      Size.
AB  - The purpose of this clinical note is to describe the performance of the Lunar
      Achilles Insight device in assessing bone quality at the calcaneus in 142
      children between the ages of 5 and 11 y accessing healthcare in Johannesburg,
      South Africa. We observed an asymmetric bimodal distribution in speed of sound
      (SOS). The minor mode consisted of unusually high SOS values (>=1625 m/s), which
      were primarily observed among children with foot size <19 cm and height <119 cm.
      Cortical regions of the bone may have been inadvertently included in the region
      of interest for smaller feet, causing unusually high SOS values. The unusually
      high SOS values indicate that the validity of SOS in this device, as it is
      currently used for measuring bone quality in young children, is questionable.
      Future studies using this device in young children should develop new methodology
      to account for smaller foot size.

PMID- 27692860
TI  - Pulmonary Arterial Hypertension after Ibuprofen Treatment for Patent Ductus
      Arteriosus in Very Low Birth Weight Infants.
AB  - OBJECTIVE: To describe the clinical course and risk factors for pulmonary
      arterial hypertension (PAH) after ibuprofen treatment to close patent ductus
      arteriosus. STUDY DESIGN: All neonates weighing < 1500 g at birth who received
      ibuprofen to close patent ductus arteriosus and were admitted to Seoul National
      University Children's Hospital's neonatal intensive care unit in 2010-2014 were
      eligible for this study. The study population was divided into the PAH and non
      PAH groups, and medical records were retrospectively reviewed. RESULTS: Of the
      144 eligible infants, 10 developed PAH (6.9%). Relative to the non-PAH group, the
      PAH group exhibited greater respiratory severity and more frequent severe
      bronchopulmonary dysplasia or death before 36 weeks postmenstrual age.
      Multivariable analysis demonstrated that lower gestational age, birth weight in
      less than the third percentile for age, maternal hypertension of pregnancy, and
      oligohydramnios were risk factors for developing PAH after ibuprofen treatment.
      CONCLUSION: A high incidence of PAH after ibuprofen treatment was observed in the
      study population. Furthermore, younger gestational age and several prenatal
      conditions were identified as risk factors for developing PAH after ibuprofen
      treatment. Additional large cohort studies are necessary to confirm our results.

PMID- 27692862
TI  - Opportunities to finance pandemic preparedness.

PMID- 27692861
TI  - Effect of Severity of Esophageal Acidification on Sleep vs Wake Periods in
      Infants Presenting with Brief Resolved Unexplained Events.
AB  - OBJECTIVES: To describe the pattern of gastroesophageal reflux (GER) events in
      wake and sleep states with increasing acid reflux index (ARI) in neonates and to
      test the hypothesis that GER-related symptoms are frequent in ARI >7% in wake
      state. STUDY DESIGN: Infants underwent 24-hour pH-impedance studies with 6-hour
      concurrent video-polysomnography studies. Data were stratified based on the 24
      hour ARI (% duration that esophageal pH is <4) into ARI < 3% (normal), ARI 3 >=
      to <=7% (intermediate), and ARI >7% (abnormal). GER frequency, clearance
      mechanisms, and symptoms were distinguished during wake state and sleep state.
      RESULTS: Total wake and sleep duration was similar (P >= .2) in all ARI groups.
      Acidic events were frequent with increasing ARI in wake state vs sleep state (P
      <= .03). The symptom index increased with increasing ARI (P <= .02) in both wake
      state and sleep state. Acid clearance time increased with increasing ARI in wake
      state (P <= .02). In ARI > 7% vs ARI <= 7%, frequency of acidic GER events was
      higher (P <= .02) in wake state and sleep state; proximal migration of acid (P =
      .03) and acid clearance time were higher in wake state (P = .0005) only. Symptom
      index was higher in ARI >7% vs ARI <= 7% in wake state (P < .0001), comparable in
      normal vs intermediate (P = .4), and higher in abnormal vs intermediate (P =
      .0004) groups. CONCLUSIONS: Severe esophageal acid exposure (ARI >7%) is
      associated with increased reflux-associated symptoms in wake state. Sleep state
      appears to be protective regardless of ARI, likely because of greater
      chemosensory thresholds. Attention to posture and movements during wake state can
      be helpful. Scrutiny for non-GER etiologies should occur for infants presenting
      with life-threatening symptoms.

PMID- 27692863
TI  - Spring-mediated distraction enterogenesis in-continuity.
AB  - PURPOSE: Distraction enterogenesis has been investigated as a novel treatment for
      patients with short bowel syndrome (SBS) but has been limited by loss of
      intestinal length during restoration and need for multiple bowel surgeries. The
      feasibility of in-continuity, spring-mediated intestinal lengthening has yet to
      be demonstrated. METHODS: Juvenile mini-Yucatan pigs underwent in-continuity
      placement of polycaprolactone (PCL) degradable springs within jejunum. Methods
      used to anchor the spring ends to the intestine included full-thickness sutures
      and a high-friction surface spring. Spring constant (k) was 6-15N/m. Bowel was
      examined for length and presence of spring at 1 to 4weeks. RESULTS: Animals
      tolerated in-continuity lengthening without bowel obstruction for up to 29days.
      In-continuity jejunum with springs demonstrated intestinal lengthening by 1.47
      fold +/-0.11. Five springs had detached prematurely, and lengthening could not be
      assessed. Histologically, in-continuity jejunum showed significantly increased
      crypt depth and muscularis thickness in comparison to normal jejunum. CONCLUSION:
      Self-expanding endoluminal springs placed in continuity could lengthen intestine
      without obstruction in a porcine model. This is the first study showing safety
      and efficacy of a self-expanding endoluminal device for distraction
      enterogenesis. This is proof-of-concept that in-continuity spring lengthening is
      feasible and demonstrates its therapeutic potential in SBS. LEVEL OF EVIDENCE:
      Level 3.

PMID- 27692864
TI  - Saturation of stool color in HSV color model is a promising objective parameter
      for screening biliary atresia.
AB  - PURPOSE: We aimed to study whether saturation in HSV color model could be a
      parameter for acholic stool and utilized for designing a mobile application for
      screening biliary atresia (BA). METHODS: Saturations of the colors in the three
      validated stool color cards (Taiwan, Japan, Britain) were read using PHOTOSHOP.
      Stools from 40 BA patients and 40 in-hospital neonates with pneumonia were
      photographed and analyzed with color-analyzing mobile applications. RESULTS:
      Saturations of normal colors in the published stool cards were all >50% (67%~99%,
      median 85%) and were all <50% (7~47%, median 25%) for abnormal colors. With
      saturation<60% as a cutoff line, acholic stools could be identified with a
      sensitivity of 100% and a specificity of 85%. CONCLUSION: Saturation of stool
      color in HSV model is a promising objective parameter for acholic stool and could
      be utilized in designing mobile APPs for screening BA. LEVEL OF EVIDENCE: Study
      of diagnostic test, level II.

PMID- 27692865
TI  - Clinical manifestation of late onset Pompe disease patients in Hong Kong.
AB  - Late onset Pompe disease is a rare inherited metabolic disease with diverse
      clinical manifestation. However, there is a lack of local data in Hong Kong. We
      aimed at performing an in-depth review of natural history of all patients in Hong
      Kong. Eleven patients were diagnosed to have the disease in Hong Kong from 2000
      to 2013. All case records were reviewed and face-to-face interviews were
      conducted to complete a questionnaire regarding the clinical manifestation and
      diagnosis of the disease. The estimated birth incidence was 1/300,000. The age of
      diagnosis ranged from 9 to 44 years; all patients were ethnic Chinese. The median
      ages of first symptoms and first medical attention were 20.5(6-44) and 29(9-44)
      years respectively. The most common initial complaint was decreased exercise
      tolerance. Two patients' first complaint was difficulty with getting up from
      lying position and failure to perform sit up. The mean time from first medical
      attention to diagnosis was 1.3 years but one patient was diagnosed 8 years later.
      Half of the patients sought medical attention due to progressive shortness of
      breath and all of them developed type 2 respiratory failure requiring ventilator
      support during the first admission. Two patients became chair-bound and seven
      patients required assisted ventilation. Late onset Pompe disease tends to have an
      earlier and more aggressive clinical presentation in Chinese and lower birth
      incidence was found in Hong Kong.

PMID- 27692866
TI  - Coronal alignment on the single-limb stance radiograph in posterolateral rotatory
      instability, osteoarthritis and healthy knees.
AB  - BACKGROUND: We aimed to determine whether coronal alignment measured on the
      single-limb stance (SLS) radiographs differs from those on the double-limb stance
      (DLS) images. We also investigated whether the size of such differences was
      affected by the knee pathology, lower limb alignment, and geometry of the tibia
      or femur. METHODS: We measured coronal alignment with mechanical tibiofemoral
      angle (MTFA) on the DLS and SLS radiographs in patients with posterolateral
      rotatory instability (PLRI, 30 knees), osteoarthritis (OA) with varus deformity
      who were scheduled for high tibial osteotomy (HTO) (60 knees), and in normal
      control (60 knees). The measurements on the SLS radiographs were compared with
      those on DLS images and the size of the differences were compared between the
      three groups. The correlation between the radiograph-related differences of
      coronal alignment and the limb alignment or geometry of tibia/femur was
      investigated. In the OA group, the size of the radiograph-related differences
      before HTO were compared with those after surgery. RESULTS: The coronal alignment
      on the SLS radiographs indicated varus accentuation compared to those on the DLS
      radiographs in the PLRI and OA groups (1.6 and 2.4 degrees , respectively), while
      it was negligible in the normal group. Greater varus inclination of the tibial
      plateau was related to greater varus accentuation (r=0.249). The HTO decreased
      the extent of varus accentuation in the OA group (reduction of varus
      accentuation=1.5 degrees ). CONCLUSIONS: Coronal alignment on the SLS radiograph
      is different from static alignment measured on the DLS radiograph, which may
      reflect dynamic alignment.

PMID- 27692867
TI  - Targeting Single Molecules in Asthma Benefits Few.
AB  - Asthma is a lung disorder triggered by various airborne factors in susceptible
      individuals. Although generally controlled, asthma can be severe and difficult to
      treat. Presently, increasing numbers of pharmaceuticals capable of blocking or
      mimicking specific endogenous molecules are undergoing clinical trials in
      asthmatic individuals whose symptoms are poorly controlled despite adherence to
      guideline therapies. Unfortunately, only a few, meticulously selected patients
      have been found to minimally benefit. These findings not only confirm that the
      molecular pathogenesis of severe asthma is variable between patients but also
      suggest that each molecular defect is likely to contribute little on its own in
      each patient. We opine that therapies targeting a specific molecular defect are
      predestined to yield marginal effects in the treatment of severe asthma.

PMID- 27692868
TI  - Chronic hypoxaemia as a molecular regulator of fetal lung development:
      implications for risk of respiratory complications at birth.
AB  - Exposure to altered intrauterine conditions during pregnancy influences both
      fetal growth and organ development. Chronic fetal hypoxaemia is a common
      pregnancy complication associated with intrauterine growth restriction (IUGR)
      that may influence the risk of infants experiencing respiratory complications at
      birth. There are a variety of signalling pathways that contribute to normal fetal
      lung development at the molecular level. The specific molecular effects of
      chronic hypoxaemia associated with IUGR on lung development are likely to be
      dependent on the specific aetiology (maternal, placental and/or fetal factors)
      that can alter hormone concentrations, oxygen and nutrient transport to the
      fetus. This review discusses molecular pathways that may contribute to altered
      fetal lung maturation following exposure to chronic hypoxaemia. Importantly,
      these studies highlight that the heterogeneity in respiratory outcomes at birth
      in this obstetric subpopulation are likely determined by the timing, severity and
      duration of chronic hypoxaemia encountered by the fetus during pregnancy.

PMID- 27692869
TI  - Understanding pharmacist success in practice: A scoping review.
AB  - OBJECTIVES: The objective was to identify literature providing a description of
      characteristics contributing to pharmacists' individual level success in
      providing advanced patient care. DESIGN: An interpretive scoping review was
      conducted to synthesize knowledge and address the study objective. SETTING:
      Searches were undertaken in Ovid MEDLINE (1946-2015), EMBASE (1974-2015), and
      International Pharmaceutical Abstracts (1970-2015). PARTICIPANTS: Not applicable.
      MAIN OUTCOME MEASURES: Specific keywords used in the search included: motivation,
      attitude, career, clinical competence, certification, pursuit of an expanded
      scope of practice, pharmacist, and success. This was not intended to be an
      exhaustive list, and every effort was made to be inclusive as the search revealed
      additional words and phrases of interest. RESULTS: A total of 93 articles were
      initially identified, 10 articles met inclusion criteria and were retained for
      full-text analysis. Most of the included articles were published in the United
      States (70%). One-third of the articles conducted semi-structured interviews, one
      third of the articles were editorials or commentaries, and the remaining articles
      collected data using surveys, knowledge assessments, and observation. Content
      analysis of the extracted definitions of success yielded 2 themes; "what
      successful pharmacists do" and "what successful pharmacists should be."
      CONCLUSION: Professional organizations representing pharmacy have made
      significant strides in advocating for pharmacists' provision of advanced patient
      care. If pharmacists are to successfully provide advanced patient care a more
      specific and practically-oriented understanding that accounts for individual and
      environmental factors of how to achieve individual-level success is needed.

PMID- 27692870
TI  - Valued characteristics of community pharmacy residency applicants.
AB  - OBJECTIVES: To determine the attributes of postgraduate year 1 (PGY1) community
      pharmacy residency applicants and candidates that are most appealing to community
      residency program directors (CRPDs). DESIGN: A 22-question online survey,
      designed to collect residency demographics, desirable characteristics for
      consideration for interview invitation (applicants), and characteristics that
      should be displayed during an interview (candidates). SETTING: American Society
      of Health-System Pharmacists (ASHP)-recognized community pharmacy residency
      programs (CPRPs). PARTICIPANTS: The CRPDs of 109 ASHP-recognized CPRPs throughout
      the United States. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Minimum
      applicant requirements; rank order of valued characteristics at application and
      interview stage of hiring process. RESULTS: The response rate was 71/109 (65.1%).
      Applicant work experience in chain pharmacy (90.1%) and independent pharmacy
      (77.5%) was most highly valued by CRPDs, with 85.9% preferring applicants with a
      minimum of 1 year or more of community pharmacy experience. A large majority of
      CPRPs (91.4%) indicated a preference for applicants who have been an officer of a
      student organization. Among CPRPs that required minimum grade point averages
      (GPAs), a mean GPA of 2.88 +/- 0.34 was reported (range 2.0 to 3.5; mode 3.0).
      Pharmacy work experience (68.1%) and letters of recommendation (59.4%) were most
      frequently cited as top factors in the decision-making process for selecting
      candidates to interview. At the interview stage, CRPDs rated interest and
      knowledge about the residency (62.3%), time management and prioritization
      (50.7%), and self-awareness and commitment to improvement (43.5%) as the most
      important skills for candidates to demonstrate. CONCLUSION: Community pharmacy
      work experience, organizational leadership experience, and positive letters of
      recommendation appear to be the most valued attributes of a community pharmacy
      residency applicant. Applicants should consider aligning themselves with these
      characteristics to successfully match to a community pharmacy residency.

PMID- 27692871
TI  - Disparities in visuo-spatial constructive abilities in Williams syndrome patients
      with typical deletion on chromosome 7q11.23.
AB  - BACKGROUND: Williams syndrome (WS) is known for its uneven cognitive abilities,
      especially the difficulty in visuo-spatial cognition, though there are some inter
      individual phenotypic differences. It has been proposed that the difficulty in
      visuo-spatial cognition of WS patients can be attributed to a haploinsufficiency
      of some genes located on the deleted region in 7q11.23, based on an examination
      of atypical deletions identified in WS patients with atypical cognitive deficits.
      According to this hypothesis, the inter-individual differences in visuo-spatial
      cognitive ability arise from variations in deletion. METHODS: We investigated
      whether there were inter-individual differences in the visuo-spatial constructive
      abilities of five unrelated WS patients with the typical deletion on chromosome
      7q11.23 that includes the candidate genes contributing visuo-spatial difficulty
      in WS patients. We used tests with three-dimensional factors such as Benton's
      three-dimensional block construction test, which are considered to be more
      sensitive than those with only two-dimensional factors. RESULTS: There were
      diverse inter-individual differences in the visuo-spatial constructive abilities
      among the present participants who shared the same typical genomic deletion of
      WS. One of the participants showed almost equivalent performances to typically
      developing adults in those tests. CONCLUSION: In the present study, we found a
      wide range of cognitive abilities in visuo-spatial construction even among the
      patients with a common deletion pattern of WS. The findings suggest that
      attributing differences in the phenotypes entirely to genetic factors such as an
      atypical deletion may not be always correct.

PMID- 27692873
TI  - Detection and Removal of Ceramic Clip Markers from Breast Tissue by Ultrasound
      Guided, Vacuum-Assisted Minimally Invasive Biopsy in a Turkey Breast Model.
AB  - This article explores the ability of sonographically guided, vacuum-assisted
      minimally invasive biopsy (VAB) to detect and remove ceramic clip markers from
      breast tissue. This is a feasibility pre-study for a clinical study using vacuum
      assisted biopsy to predict pathologic complete response of breast cancer. Twenty
      six ceramic clip markers were placed in five turkey breasts. Clip markers were
      then detected sonographically and removed using VAB by experienced physicians.
      Quality of visibility was graded by the performing doctors. The specimens were
      examined macroscopically to see if they contained the clip marker. The main
      outcome measure was the accuracy of VAB to detect and remove the clip marker. The
      VAB device was inspected for any damage possibly caused by hitting the clip
      marker. The clip markers were detected in 25 cases (96.2%). Twenty clip markers
      (76.9%) were removed completely by VAB and five (19.2%) were partially removed.
      One clip marker (3.8%) was not removed. On average, detection of the clip marker
      took 67 s and the biopsy took 178 s. Quality of visibility was mostly graded as
      very good (14 cases/53.8%) or good (nine cases/34.6%), and in all of these cases
      the clip marker was at least partially removed. The clip marker was visible and
      removed in the vast majority of the cases. VAB is able to remove the clip marker
      in integrity without causing damage to the system.

PMID- 27692872
TI  - Using Speed of Sound Imaging to Characterize Breast Density.
AB  - A population of 165 women with negative mammographic screens also received an
      ultrasound tomography (UST) examination at the Karmanos Cancer Institute in
      Detroit, MI. Standard statistical techniques were employed to measure the
      associations between the various mammographic- and UST-related density measures
      and various participant characteristics such as age, weight and height. The
      mammographic percent density (MPD) was found to have similar strength
      associations with UST mean sound speed (Spearman coefficient, rs = 0.722, p <
      0.001) and UST median sound speed (rs = 0.737, p < 0.001). Both were stronger
      than the associations between MPD with two separate measures of UST percent
      density, a k-means (rs = 0.568, p < 0.001) or a threshold (rs = 0.715, p < 0.001)
      measure. Segmentation of the UST sound speed images into dense and non-dense
      volumes showed weak to moderate associations with the mammographically equivalent
      measures. Relationships were found to be inversely and weakly associated between
      age and the UST mean sound speed (rs = -0.239, p = 0.002), UST median sound speed
      (rs = -0.226, p = 0.004) and MPD (rs = -0.204, p = 0.008). Relationships were
      found to be inversely and moderately associated between body mass index (BMI) and
      the UST mean sound speed (rs = -0.429, p < 0.001), UST median sound speed (rs = 
      0.447, p < 0.001) and MPD (rs = -0.489, p < 0.001). The results confirm and
      strengthen findings presented in previous work indicating that UST sound speed
      imaging yields viable markers of breast density in a manner consistent with
      mammography, the current clinical standard. These results lay the groundwork for
      further studies to assess the role of sound speed imaging in risk prediction.

PMID- 27692874
TI  - Comparison between Quantitative Stiffness Measurements and Ultrasonographic
      Findings of Fresh Carotid Plaques.
AB  - Using a stiffness meter, we quantitatively measured the stiffness of fresh
      plaques that had been excised by carotid endarterectomy. The objective of this
      study was to clarify the correlation between plaque stiffness and pre-operative
      carotid ultrasonographic findings, and predict the stiffness of plaques before
      surgery by comparison with the stiffness of common items. The study population
      comprised 44 patients (44 lesions) who had undergone carotid endarterectomy at
      our institution between December 2009 and October 2014. The stiffness of excised
      fresh plaques was measured using a stiffness meter and compared with the pre
      operative echographic findings for the plaques and the stiffness of selected
      foods and common items. The mean stiffness value for all plaques was 4.52 +/-
      3.30 MPa (mean +/- standard deviation). The plaques exhibiting calcification were
      significantly harder (p = 0.001). On classification of lesions on the basis of
      echographic findings, plaque hardness was in the order low-echoic (15 lesions) <
      iso-echoic (20 lesions) < high-echoic (9 lesions) (p = 0.02). The stiffness of
      the low-echoic group was equivalent to that of tofu or sliced cheese, whereas the
      plaques in the iso- and high-echoic groups exhibited stiffness similar to that of
      ham and a plastic eraser, respectively. A significant correlation was observed
      between the quantitative stiffness values of carotid plaques and their brightness
      on carotid ultrasonography. Using these data, operators might be able to predict
      plaque stiffness from pre-operative echographic findings. In addition, it might
      be useful for operators to compare such quantitative stiffness measurements with
      stiffness data for foods and common items to gain an understanding of the state
      of the target plaque before treatment.

PMID- 27692875
TI  - Bioactive molecules derived from umbilical cord mesenchymal stem cells.
AB  - Umbilical cord mesenchymal stem cells (UCMSCs) retain their intrinsic stem cell
      potential while at the same time displaying high proliferation rates, powerful
      differentiation capacity, and low immunogenicity. They can also secrete multiple
      bioactive molecules that exert specific physiological functions. Thus, UCMSCs
      represent excellent candidates for cell therapy in regenerative medicine and
      tissue engineering. Abundant preclinical research on different disease models has
      shown that UCMSCs can accelerate wound or nerve damage recovery and suppress
      tumor progression. In fact, UCMSCs are thought to possess a higher therapeutic
      potential than MSCs derived from other tissues. Increasing evidence suggests that
      the mechanism underlying UCSMCs efficacy depends mostly on cell secretions, in
      contrast to the early paradigm of cell replacement and differentiation. In this
      review, we discuss UCMSCs biological characteristics, their secretome-based
      therapeutic mechanism, and potential applications.

PMID- 27692876
TI  - Expression of nitric oxide-containing structures in the rat carotid body.
AB  - The carotid body (CB) is a major peripheral arterial chemoreceptor organ that
      evokes compensatory reflex responses so as to maintain gas homeostasis. It is
      dually innervated by sensory fibers from petrosal ganglion (PG) neurons, and
      autonomic fibers from postganglionic sympathetic neurons of the superior cervical
      ganglion (SCG) and parasympathetic vasomotor fibers of intrinsic ganglion cells
      in the CB. The presence of nitric oxide (NO), a putative gaseous neurotransmitter
      substance in a number of neuronal and non-neuronal structures, was examined in
      the CB, PG and SCG of the rat using nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d) histochemistry, nitric oxide synthase (NOS)
      immunohistochemistry and retrograde tracing. One week after injecting the
      retrograde tracer Fast Blue (FB) in the CB, we found that a subset of perikarya
      in the caudal portions of the PG and SCG were FB-labeled. Histochemistry and
      immunohistochemistry revealed that the majority of large- and medium-sized PG and
      SCG cells were NADPH-d positive and displayed a strong NOS immunostaining. We
      also observed that many varicose nerve fibers penetrating the CB and enveloping
      the glomus cells and blood vessels were NADPH-d reactive and expressed the
      constitutive isoforms of NOS, nNOS and eNOS. In addition, some autonomic
      microganglion cells embedded within, or located at the periphery of the CB, and
      not glomus or sustentacular cells were nNOS-immunopositive while CB
      microvasculature expressed eNOS. The present results suggest that NO is a
      transmitter in the autonomic nerve endings supplying the CB and is involved in
      efferent chemoreceptor inhibition by a dual mechanism.

PMID- 27692877
TI  - Impact of endocrine disrupting chemicals on onset and development of female
      reproductive disorders and hormone-related cancer.
AB  - A growing body of evidence suggests that exposure to chemical substances
      designated as endocrine disrupting chemicals (EDCs) due to their ability to
      disturb endocrine (hormonal) activity in humans and animals, may contribute to
      problems with fertility, pregnancy, and other aspects of reproduction. The
      presence of EDCs has already been associated with reproductive malfunction in
      wildlife species, but it remains difficult to prove causal relationships between
      the presence of EDCs and specific reproductive problems in vivo, especially in
      females. On the other hand, the increasing number of experiments with laboratory
      animals and in vitro research indicate the ability of different EDCs to influence
      the normal function of female reproductive system, and even their association
      with cancer development or progression. Research shows that EDCs may pose the
      greatest risk during prenatal and early postnatal development when organ and
      neural systems are forming. In this review article, we aim to point out a
      possible contribution of EDCs to the onset and development of female reproductive
      disorders and endocrine-related cancers with regard to the period of exposure to
      EDCs and affected endpoints (organs or processes).

PMID- 27692878
TI  - Hybrid robotic systems for upper limb rehabilitation after stroke: A review.
AB  - In recent years the combined use of functional electrical stimulation (FES) and
      robotic devices, called hybrid robotic rehabilitation systems, has emerged as a
      promising approach for rehabilitation of lower and upper limb motor functions.
      This paper presents a review of the state of the art of current hybrid robotic
      solutions for upper limb rehabilitation after stroke. For this aim, studies have
      been selected through a search using web databases: IEEE-Xplore, Scopus and
      PubMed. A total of 10 different hybrid robotic systems were identified, and they
      are presented in this paper. Selected systems are critically compared considering
      their technological components and aspects that form part of the hybrid robotic
      solution, the proposed control strategies that have been implemented, as well as
      the current technological challenges in this topic. Additionally, we will present
      and discuss the corresponding evidences on the effectiveness of these hybrid
      robotic therapies. The review also discusses the future trends in this field.

PMID- 27692879
TI  - Drug Repurposing: New Treatments for Zika Virus Infection?
AB  - To date, no antiviral agents have been approved for treating Zika virus (ZIKV)
      infection. Two recent drug-repurposing studies published in Cell Host & Microbe
      and Nature Medicine demonstrated that screening FDA-approved drugs for antiviral
      activity is a promising strategy for identifying therapeutics with novel activity
      against ZIKV infection.

PMID- 27692881
TI  - Decreased vaccine antibody titers following exposure to multiple metals and
      metalloids in e-waste-exposed preschool children.
AB  - We explored acquired immunity resulting from vaccination in 3 to 7-year-old
      children, chronically exposed to multiple heavy metals and metalloids, in an e
      waste recycling area (Guiyu, China). Child blood levels of ten heavy metals and
      metalloids, including lead (Pb), arsenic (As), mercury (Hg), chromium (Cr),
      cadmium (Cd), manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn) and selenium
      (Se), and seven vaccine antibodies (diphtheria, pertussis, tetanus, hepatitis B,
      Japanese encephalitis, polio, measles) were measured. The exposed group had
      higher levels of blood Pb, Mn, Cu, Zn and Cr compared to the reference group (P <
      0.05). Levels of all vaccine antibodies in the exposed group were significantly
      lower than in the reference group (P < 0.01). All vaccine antibodies negatively
      correlated with blood concentrations of Cu, Zn and Pb, based on spearman rank
      correlation analysis. Multiple logistic regression and univariate analyses
      identified the location of residence (Guiyu), high blood Pb (>10 MUg/dL) and high
      blood Cu and Zn (upper median value of each group) to be inversely associated
      with seven antibody titers. Antibody titers increased with age, BMI, high blood
      Mn (>15 MUg/L), and high blood Cd and Ni (upper median value of each group).
      Results suggest multiple heavy metal and metalloid exposure, especially to Pb, Zn
      and Cu, may be a risk factor inhibiting the development of child immunity,
      resulting in decreased child antibody levels against vaccines.

PMID- 27692880
TI  - Urinary Tract Infection: Pathogenesis and Outlook.
AB  - The clinical syndromes comprising urinary tract infection (UTI) continue to exert
      significant impact on millions of patients worldwide, most of whom are otherwise
      healthy women. Antibiotic therapy for acute cystitis does not prevent
      recurrences, which plague up to one fourth of women after an initial UTI. Rising
      antimicrobial resistance among uropathogenic bacteria further complicates
      therapeutic decisions, necessitating new approaches based on fundamental
      biological investigation. In this review, we highlight contemporary advances in
      the field of UTI pathogenesis and how these might inform both our clinical
      perspective and future scientific priorities.

PMID- 27692882
TI  - Updated national emission of perfluoroalkyl substances (PFASs) from wastewater
      treatment plants in South Korea.
AB  - A nationwide emission estimate of perfluoroalkyl substances (PFASs) from
      wastewater treatment plants (WWTPs) is required to understand the source-receptor
      relationship of PFASs and to manage major types of WWTPs. In this study, the
      concentrations of 13 PFASs (8 perfluorocarboxylic acids, 3 perfluoroalkane
      sulfonates, and 2 intermediates) in wastewater and sludge from 81 WWTPs in South
      Korea were collected. The emission pathways of PFASs were redefined, and then the
      national emission of PFASs from WWTPs was rigorously updated. In addition to the
      direct calculations, Monte Carlo simulations were also used to calculate the
      likely range of PFAS emissions. The total (Sigma13PFAS) emission (wastewater +
      sludge) calculated from the direct calculation with mean concentrations was 4.03
      ton/y. The emissions of perfluorooctanoic acid (PFOA, 1.19 ton/y) and
      perfluorooctane sulfonate (PFOS, 1.01 ton/y) were dominant. The Monte Carlo
      simulations suggested that the realistic national emission of Sigma13PFASs is
      between 2 ton/y and 20 ton/y. Combined WWTPs treating municipal wastewater from
      residential and commercial areas were identified as a major emission source,
      contributing 65% to the total PFAS emissions. The Han and Nakdong Rivers were the
      primary contaminated rivers, receiving 89% of the total PFAS discharge from
      WWTPs. The results and methodologies in this study can be useful to establish a
      management policy for PFASs.

PMID- 27692883
TI  - Arthropod communities in a selenium-contaminated habitat with a focus on ant
      species.
AB  - The selenium contamination event that occurred at Kesterson Reservoir (Merced
      Co., CA) during the 1970-80s is a frequently cited example for the negative
      effects of contamination on wildlife. Despite the importance of arthropods for
      ecosystem services and functioning, relatively little information is available as
      to the impacts of pollution on arthropod community dynamics. We conducted surveys
      of the arthropod community present at Kesterson Reservoir to assess the impacts
      of selenium contamination on arthropod diversity, with a focus on ant species
      richness, composition and density. Trophic groups were compared to determine
      which arthropods were potentially receiving the greatest selenium exposure. Plant
      samples were analyzed to determine the selenium content by site and by location
      within plant. Soil concentrations varied across the study sites, but not across
      habitat types. Topsoil contained higher levels of selenium compared to core
      samples. Plants contained similar concentrations of selenium in their leaves,
      stems and flowers, but flowers contained the greatest range of concentrations.
      Individuals within the detritivores/decomposers and predators accumulated the
      greatest concentrations of selenium, whereas nectarivores contained the lowest
      concentrations. Species composition differed across the sites: Dorymyrmex bicolor
      was located only at the site containing the greatest soil selenium concentration,
      but Solenopsis xyloni was found at most sites and was predominant at six of the
      sites. Selenium concentrations in ants varied by species and collection sites.
      Nest density was also found to differ across sites, but was not related to soil
      selenium or any of the habitat variables measured in our study. Selenium was not
      found to impact species richness, but was a significant variable for the
      occurrence of two out of the eight native species identified.

PMID- 27692884
TI  - Assessment of the aryl hydrocarbon receptor-mediated activities of polycyclic
      aromatic hydrocarbons in a human cell-based reporter gene assay.
AB  - Activation of the aryl hydrocarbon receptor (AhR)-mediated activity is one of key
      events in toxicity of polycyclic aromatic hydrocarbons (PAHs). Although various
      classes of AhR ligands may differentially activate human and rodent AhR, there is
      presently a lack of data on the human AhR-inducing relative potencies (REPs) of
      PAHs. Here, we focused on estimation of the AhR-mediated activities of a large
      set of environmental PAHs in human gene reporter AZ-AhR cell line, with an aim to
      develop the human AhR-based REP values with potential implications for risk
      assessment of PAHs. The previously identified weakly active PAHs mostly failed to
      activate the AhR in human cells. The order for REPs of individual PAHs in human
      cells largely corresponded with the available data from rodent-based experimental
      systems; nevertheless, we identified differences up to one order of magnitude in
      REP values of PAHs between human and rodent cells. Higher REP values were found
      in human cells for some important environmental contaminants or suspected
      carcinogens, such as indeno[1,2,3-cd]pyrene, benz[a]anthracene or
      benzo[b]fluoranthene, while lower REP values were determined for methyl
      substituted PAHs. Our results also indicate that a different rate of metabolism
      for individual PAHs in human vs. rodent cells may affect estimation of REP values
      in human cell-based assay, and potentially alter toxicity of some compounds, such
      as benzofluoranthenes, in humans. We applied the AZ-AhR assay to evaluation of
      the AhR-mediated activity of complex mixtures of organic compounds associated
      with diesel exhaust particles, and we identified the polar compounds present in
      these mixtures as being particularly highly active in human cells, as compared
      with rodent cells. The present data suggest that differences may exist between
      the AhR-mediated potencies of PAHs in human and rodent cells, and that the AhR
      mediated effects of polar PAH derivatives and metabolites in human cell models
      deserve further attention.

PMID- 27692885
TI  - Air pollution and asthma attacks in children: A case-crossover analysis in the
      city of Chongqing, China.
AB  - Data on particulate matter of diameter <2.5 MUm (PM2.5) in the city of Chongqing
      were first announced in 2013. We wished to assess the effects of pollutants on
      asthmatic children in Chongqing, China. Daily numbers of hospital visits because
      of asthma attacks in children aged 0-18 years in 2013 were collected from the
      Children's Hospital of Chongqing Medical University. Data on pollutants were
      accessed from the nine air quality-monitoring stations in Chongqing. A time
      stratified case-crossover design was applied and conditional logistic regression
      was undertaken to analyze the data. We found that short-term exposure to PM10,
      PM2.5, sodium dioxide, nitrogen and carbon monoxide could trigger hospital visits
      for asthma in children. Nitrogen dioxide had an important role, whereas ozone had
      no effect.

PMID- 27692887
TI  - Novel use of field-portable-XRF for the direct analysis of trace elements in
      marine macroalgae.
AB  - Samples of dried marine macroalgae (Fucus serratus, Palmaria palmata and Ulva
      lactuca) have been analysed for trace elements by a novel, non-destructive
      approach involving a Niton field-portable-X-ray fluorescence (FP-XRF)
      spectrometer configured in a low density plastics mode with thickness correction.
      Detection limits for a 200-s counting time ranged from <5 MUg g-1 for As and Pb
      in F. serratus and As in P. palmata to several tens of MUg g-1 for Cd, Sb and Sn
      in all species tested. Arsenic, Cu, Pb and Zn were detected by the XRF in samples
      collected from a protected beach (n = 18) and in samples therefrom that had been
      exposed to additional aqueous elements in combination (n = 72) with
      concentrations returned (in MUg g-1) ranging from 3.9 to 39.7 for As, 13.0 to 307
      for Cu, 6.1 to 14.7 for Pb and 12.5 to 522 for Zn. Independent measurements of
      trace elements in the macroalgae by ICP-MS following nitric acid digestion
      revealed a direct and significant proportionality with concentrations returned by
      the XRF, with slopes of the XRF-ICP relationships (As = 1.0; Cu = 2.3; Pb = 2.4;
      Zn = 1.7) that can be used to calibrate the instrument for direct measurements.
      The approach shows potential for the in situ monitoring of macroalgae in coastal
      regions that is currently being investigated.

PMID- 27692886
TI  - Uptake and subcellular distribution of triclosan in typical hydrophytes under
      hydroponic conditions.
AB  - The increasing discharge of pharmaceuticals and personal care products (PPCPs)
      into the environment has generated serious public concern. The recent awareness
      of the environmental impact of this emerging class of pollutants and their
      potential adverse effects on human health have been documented in many reports.
      However, information regarding uptake and intracellular distribution of PPCPs in
      hydrophytes under hydroponic conditions, and potential human exposure is very
      limited. A laboratory experiment was conducted using 14C-labeled triclosan (TCS)
      to investigate uptake and distribution of TCS in six aquatic plants (water
      spinach, purple perilla, cress, penny grass, cane shoot, and rice), and the
      subcellular distribution of 14C-TCS was determined in these plants. The results
      showed that the uptake and removal rate of TCS from nutrient solution by
      hydrophytes followed the order of cress (96%) > water spinach (94%) > penny grass
      (87%) > cane shoot (84%) > purple perilla (78%) > rice (63%) at the end of
      incubation period (192 h). The range of 14C-TCS content in the roots was 94.3%
      99.0% of the added 14C-TCS, and the concentrations in roots were 2-3 orders of
      magnitude greater than those in shoots. Furthermore, the subcellular fraction
      concentration factor (3.6 * 102-2.6 * 103 mL g-1), concentration (0.58-4.47 MUg g
      1), and percentage (30%-61%) of 14C-TCS in organelles were found predominantly
      greater than those in cell walls and/or cytoplasm. These results indicate that
      for these plants, the roots are the primary storage for TCS, and within plant
      cells organelles are the major domains for TCS accumulation. These findings
      provide a better understanding of translocation and accumulation of TCS in
      aquatic plants at the cellular level, which is valuable for environmental and
      human health assessments of TCS.

PMID- 27692889
TI  - Effects of slurry properties on simultaneous removal of SO2 and NO by ammonia
      Fe(II)EDTA absorption in sintering plants.
AB  - Simultaneous removal of SO2 and NO by ammonia-Fe(II)EDTA absorption has become a
      research focus in recent years. In order to get useful data for further
      industrialization, in this work the practical operating conditions of the
      sintering plant were simulated in a pilot-scale reactor in order to explore the
      effects of slurry properties on simultaneous removal of SO2 and NO. It was not
      conducive to the absorption of NO when (NH4)2SO4 concentration and slurry
      temperature had been increased. The initial NO removal efficiency decreased from
      90.63% to 44.12% as the (NH4)2SO4 concentration increased from zero to 3.5 mol/L.
      With the increasing of Fe(II)EDTA concentration, SO32- concentration and pH value
      of absorption liquid and the absorption capacity of NO by Fe(II)EDTA solution
      increased. Especially the existence of SO32- ions in slurry had significantly
      improved the service life of chelating agents. The NO removal efficiency only
      decreased by 16.46% with the SO32- concentration of 0.3 mol/L after 30-min of
      operation. The chloride ions had no effects on the absorption of SO2 and NO. The
      results indicated that changes of slurry properties had different effects on
      simultaneous removal of SO2 and NO by ammonia-Fe(II)EDTA solution. The basic data
      offered by the experiments could effectively contribute to further industrial
      applications.

PMID- 27692888
TI  - Effective degradation of methylisothiazolone biocide using ozone: Kinetics,
      mechanisms, and decreases in toxicity.
AB  - Methylisothiazolone (MIT) is a common biocide that is widely used in water
      desalination reverse-osmosis processes. The transformation of MIT during water
      treatment processes is poorly understood. The kinetics and mechanisms involved in
      the degradation of MIT during ozonation were investigated in this study.
      Ozonation was found to be a useful way of degrading MIT in water, and the
      degradation rate constant was 0.11 (+/-0.1) * 103 L/(mol.s). The degradation rate
      constant did not change when the pH was increased from 3 to 9. The pre
      exponential factor A and the activation energy Ea for the ozonation process were
      7.564 * 1013 L/(mol.s) and 66.74 kJ/mol, respectively. The decrease in the MIT
      concentration and the amount of ozone consumed were measured, and the
      stoichiometric factor alpha for the ozone consumption to MIT removal ratio was
      found to be 1.8. Several ozonation products were detected using time-of-flight
      mass spectrometry. Almost 32% of the organic sulfur in the MIT was oxidized to
      release sulfate ions, which caused a decrease in pH. Sulfur atoms were oxidized
      to sulfone species and then hydrolyzed to give sulfate during ozonation. Addition
      reactions involving carbon-carbon double bonds and the oxidation of alpha-carbon
      atoms also occurred. MIT was found to be lethal to Daphnia magna Straus (D.
      magna) with a median lethal concentration of 18.2 MUmol/L. Even though the
      primary ozonation products of MIT still showed some toxicity to D. magna, ozone
      could minimize the toxic effect after a long reaction time.

PMID- 27692890
TI  - Mainstreaming conservation agriculture in Malawi: Knowledge gaps and
      institutional barriers.
AB  - Conservation agriculture (CA) practices of reduced soil tillage, permanent
      organic soil coverage and intercropping/crop rotation, are being advocated
      globally, based on perceived benefits for crop yields, soil carbon storage, weed
      suppression, reduced soil erosion and improved soil water retention. However,
      some have questioned their efficacy due to uncertainty around the performance and
      trade-offs associated with CA practices, and their compatibility with the diverse
      livelihood strategies and varied agro-ecological conditions across African
      smallholder systems. This paper assesses the role of key institutions in Malawi
      in shaping pathways towards more sustainable land management based on CA by
      outlining their impact on national policy-making and the design and
      implementation of agricultural development projects. It draws on interviews at
      national, district and project levels and a multi-stakeholder workshop that
      mapped the institutional landscape of decision-making for agricultural land
      management practices. Findings identify knowledge gaps and institutional barriers
      that influence land management decision-making and constrain CA uptake. We use
      our findings to set out an integrated roadmap of research needs and policy
      options aimed at supporting CA as a route to enhanced sustainable land management
      in Malawi. Findings offer lessons that can inform design, planning and
      implementation of CA projects, and identify the multi-level institutional support
      structures required for mainstreaming sustainable land management in sub-Saharan
      Africa.

PMID- 27692891
TI  - Sustainable infrastructure: A review and a research agenda.
AB  - This paper proposes a taxonomy of themes and a research agenda on sustainable
      infrastructure, with a focus on sustainable buildings (SB) and green
      infrastructure (GI). The citation databases of Web of Science formed the basis
      for a novel strategic thematic analysis of co-citation and co-occurrence of
      keywords with a longitudinal identification of themes during the last two decades
      (from 1995 to 2015) of an emerging and ever growing research area. SI is a
      multidisciplinary endeavour, including a diversified array of disciplines as
      general engineering, environmental ecology, construction, architecture, urban
      planning, and geography. This paper traces that the number of publications in SI
      is growing exponentially since 2003. Over 80% of total citations are concentrated
      in less than 10% of papers spread over a large number of journals. Most
      publications originate from the United States, Europe, Australia, and Asia. The
      main research streams in SI are green infrastructure, sustainable buildings, and
      assessment methods. Emerging and prevailing research themes include
      methodological issues of cost-effectiveness, project management and assessment
      tools. Substantive issues complement the research agenda of emerging themes in
      the areas of integration of human, economic and corporate social responsibility
      values in environmental sustainability, urban landscape and sustainable drainage
      systems, interdisciplinary research in green material, integrated policy research
      in urbanization, agriculture and nature conservation, and extensions of Green
      Building (GB) and GI to cities of developing countries.

PMID- 27692892
TI  - The role of nature-based infrastructure (NBI) in coastal resiliency planning: A
      literature review.
AB  - The use of nature-based infrastructure (NBI) has attracted increasing attention
      in the context of protection against coastal flooding. This review is focused on
      NBI approaches to improve coastal resilience in the face of extreme storm events,
      including hurricanes. We not only consider the role of NBI as a measure to
      protect people and property but also in the context of other ecological goods and
      services provided by tidal wetlands including production of fish and shellfish.
      Although the results of many studies suggest that populated areas protected by
      coastal marshes were less likely to experience damage when exposed to the full
      force of storm surge, it was absolutely critical to place the role of coastal
      wetlands into perspective by noting that while tidal marshes can reduce wave
      energy from low-to-moderate-energy storms, their capacity to substantially reduce
      storm surge remains poorly quantified. Moreover, although tidal marshes can
      reduce storm surge from fast moving storms, very large expanses of habitat are
      needed to be most effective, and for most urban settings, there is insufficient
      space to rely on nature-based risk reduction strategies alone. The success of a
      given NBI method is also context dependent on local conditions, with potentially
      confounding influences from substrate characteristics, topography, near shore
      bathymetry, distance from the shore and other physical factors and human drivers
      such as development patterns. Furthermore, it is important to better understand
      the strengths and weaknesses of newly developed NBI projects through rigorous
      evaluations and characterize the local specificities of the particular built and
      natural environments surrounding these coastal areas. In order for the relevant
      science to better inform policy, and assist in land-use challenges, scientists
      must clearly state the likelihood of success in a particular circumstance and set
      of conditions. We conclude that "caution is advised" before selecting a
      particular NBI method as there is no "one size fits all" solution to address site
      specific conditions.

PMID- 27692893
TI  - Benefits transfer and the aquatic environment: An investigation into the context
      of fish passage improvement.
AB  - We present findings from a choice experiment investigating improvements in the
      aquatic environment from mitigation of barriers to fish passage. Implemented at a
      local and national level, results reveal positive preferences for increased
      numbers of fish species as well as fish abundance. In addition, we examine if in
      this case the willingness to pay estimates are suitable for direct transfer
      between national and local settings. For both samples, we consider the extent to
      which stated attribute non-attendance impacts estimates of willingness to pay and
      the potential ability of researchers to transfer values between contexts.
      Implications of the use of benefit transfer within this policy context are
      discussed in light of our findings.

PMID- 27692895
TI  - An evaluation of forums for discussions on inclusion in a college of nursing.
AB  - BACKGROUND: The lack of diversity in the nursing profession could be an outcome
      of unconscious biases. Forums allowing the personal reflection and discourse of
      these unconscious biases are needed in order for a diverse and inclusive learning
      environment to exist. PURPOSE: The purpose of this study was to describe the
      experiences of students, staff, faculty members, and guests participating in a
      forum on diversity and inclusion. METHODS: An exploratory design was used to
      understand the experiences of college of nursing students, staff, faculty
      members, and guests who participated in a diversity and inclusion intervention
      sponsored by the college of nursing's Diversity Advisory Council. Attendees to 12
      diversity book club, movie night, and speaker series' sessions completed a
      program evaluation tool. Responses to open-ended items were analyzed using a
      constant comparative analysis method.Responses from 197 participants were
      analyzed. Eight book club, seven movie night, and six speaker series' themes were
      derived from the data including Humanness is Universal, Personal Connection, The
      Problem, Awareness of Disparity, Make a Difference, and No Change. DISCUSSION:
      Participants at each session critically dialogued about their conscious and
      unconscious biases. The study findings show that participants also were able to
      document changes to their knowledge, attitudes, and behaviors in relation to the
      historically oppressed populations focused on during the intervention activities.
      CONCLUSION: Education entertainment as used in this study was a valuable
      mechanism for hosting conversations about diversity and inclusion.

PMID- 27692894
TI  - mRNA expression profiles of colorectal liver metastases as a novel biomarker for
      early recurrence after partial hepatectomy.
AB  - BACKGROUND: Identification of specific risk groups for recurrence after surgery
      for isolated colorectal liver metastases (CRLM) remains challenging due to the
      heterogeneity of the disease. Classical clinicopathologic parameters have limited
      prognostic value. The aim of this study was to identify a gene expression
      signature measured in CRLM discriminating early from late recurrence after
      partial hepatectomy. METHODS: CRLM from two patient groups were collected: I)
      with recurrent disease <=12 months after surgery (N = 33), and II) without
      recurrences and disease free for >=36 months (N = 30). The patients were
      clinically homogeneous; all had a low clinical risk score (0-2) and did not
      receive (neo-) adjuvant chemotherapy. Total RNA was hybridised to Illumina
      arrays, and processed for analysis. A leave-one-out cross validation (LOOCV)
      analysis was performed to identify a prognostic gene expression signature.
      RESULTS: LOOCV yielded an 11-gene profile with prognostic value in relation to
      recurrent disease <=12 months after partial hepatectomy. This signature had a
      sensitivity of 81.8%, with a specificity of 66.7% for predicting recurrences
      (<=12 months) versus no recurrences for at least 36 months after surgery (X2 P <
      0.0001). CONCLUSION: The current study yielded an 11-gene signature at mRNA level
      in CRLM discriminating early from late or no relapse after partial hepatectomy.

PMID- 27692896
TI  - Molecular Beacon Nano-Sensors for Probing Living Cancer Cells.
AB  - Heterogeneities and oncogenesis essentially result from proteomic disorders
      orchestrated by changes in DNA and/or cytoplasmic mRNA. These genetic
      fluctuations, however, cannot be decoded through conventional label-free methods
      (e.g., patch clamps, electrochemical cellular biosensors, etc.) or morphological
      characterization. Molecular beacons (MBs) have recently emerged as efficient
      probes for interrogating biomarkers in live cancer cells. MBs hybridize with
      their intracellular targets (e.g., mRNAs, DNAs, or proteins), emitting a
      fluorescent signal that can be quantified and correlated with the expression
      levels of their targets. In this review we discuss MB probes with different
      delivery platforms for intracellular probing as well as novel MB designs for
      detecting a variety of targets in living cancer cells. Finally, we describe
      current trends in MB-based intracellular biosensors.

PMID- 27692898
TI  - Peri-implant bone loss around platform-switched Morse taper connection implants:
      a prospective 60-month follow-up study.
AB  - The aim of this study was to measure the crestal bone level changes at 60 months
      of follow-up and to evaluate the influence of biologically relevant, anatomical,
      and implant-related variables. A prospective study design was used. STROBE
      guidelines were followed. A total of 576 implants were inserted in 270 patients
      needing an implant-supported, partial, fixed dental prosthesis or a single crown.
      Standardized peri-apical radiographs were obtained at 2 months (time of implant
      abutment connection and prosthetic loading) and 60 months of follow-up.
      Descriptive statistics were used and inter- and intra-examiner reliability
      determined. A mixed model was used to evaluate the predictor variables. The
      correlation among multiple implants inserted in a single patient was considered.
      Significance was assessed using the type 3 test. Sensitivity analyses, least
      squares means analyses, t-tests, and chi2 tests were also conducted. The
      statistical analysis was performed at the implant level; P<0.05 indicated
      statistical significance. At the 60-month follow-up, the mean marginal bone
      remodelling was -0.59+/-1.34mm (range -5.70 to 3.65mm). Marginal bone loss was
      significantly influenced by implant depth, implant location, and the interactions
      implant depth*jaw, implant location*timing of implant placement, and jaw*implant
      diameter. At the 60-month follow-up, a low mean marginal bone loss was found,
      which was significantly higher with subcrestal implants and anterior implants.

PMID- 27692897
TI  - Optogenetic Immunomodulation: Shedding Light on Antitumor Immunity.
AB  - Microbial opsin-based optogenetic tools have been transformative for
      neuroscience. To extend optogenetic approaches to the immune system to remotely
      control immune responses with superior spatiotemporal precision, pioneering tools
      have recently been crafted to modulate lymphocyte trafficking, inflammasome
      activation, dendritic cell (DC) maturation, and antitumor immunity through the
      photoactivation of engineered chemokine receptors and calcium release-activated
      calcium channels. We highlight herein some conceptual design strategies for
      installing light sensitivities into the immune signaling network and, in
      parallel, we propose potential solutions for in vivo optogenetic applications in
      living organisms with near-infrared light-responsive upconversion nanomaterials.
      Moreover, to move beyond proof-of-concept into translational applications, we
      discuss future prospects for integrating personalized immunoengineering with
      optogenetics to overcome critical hurdles in cancer immunotherapy.

PMID- 27692899
TI  - Isothermal Amplification Strategies for Detection in Microfluidic Devices.
AB  - Isothermal rolling circle amplification (RCA) is used to detect nucleic and non
      nucleic acid biomarkers with high sensitivity. Immuno-RCA, the specific detection
      of proteins via antigen-antibody recognition, has been miniaturized for
      microfluidic platforms to reduce reagent and sample consumption, accelerate
      reaction kinetics, and enhance the sensitivity and specificity of detection.

PMID- 27692901
TI  - Modifiers of LRRK2 parkinsonism: new therapeutic targets.

PMID- 27692900
TI  - Fine particulate matter exposure and olfactory dysfunction among urban-dwelling
      older US adults.
AB  - OBJECTIVES: The olfactory nerve is anatomically susceptible to injury from
      pollution in inspired air, but there are no large-scale epidemiologic studies
      investigating this relationship. METHODS: Cross-sectional study using data from
      the National Social Life, Health, and Aging Project, a representative sample of
      home-dwelling US adults age 57-85 years. Olfactory function was tested using a
      validated 5-item odor identification test (Sniffin' Sticks). Exposure to fine
      particulate matter (PM2.5) at each respondent's home was estimated as 1-12 month
      moving averages prior to olfactory assessment using validated spatio-temporal
      models. RESULTS: Olfactory dysfunction was significantly associated with PM2.5
      exposures averaged over 3-12 months in urban-dwelling respondents. The strongest
      effect was for 6 month average exposure (per 1-IQR increase in PM2.5: OR 1.28,
      95% CI 1.05, 1.55) adjusting for age, gender, race/ethnicity, education,
      cognition, comorbidity, smoking, and the season. Interestingly, the most
      deleterious effects were observed among the youngest respondents, 57-64 years
      old, and those living in the northeast and south. CONCLUSIONS: We show for the
      first time that air pollution exposure is associated with poor olfaction among
      urban-living, older US adults.

PMID- 27692903
TI  - Intubated Versus Nonintubated General Anesthesia for Video-Assisted Thoracoscopic
      Surgery-A Case-Control Study.
AB  - OBJECTIVE: General anesthesia with endobronchial intubation and one-lung positive
      pressure ventilation always has been considered mandatory for thoracic surgery.
      Recently, there has been interest in nonintubated techniques for video-assisted
      thoracoscopic surgery (VATS) in awake and sedated patients. The authors' center
      developed a nonintubated technique with spontaneous ventilation with the patient
      under general anesthesia using a supraglottic airway device. The authors believe
      that this was the first study to compare a nonintubated general anesthetic
      technique with an intubated general anesthetic technique for VATS. DESIGN:
      Retrospective, observational study. SETTING: Specialist cardiothoracic hospital
      in the United Kingdom. PARTICIPANTS: All patients who underwent elective minor
      VATS over 8 months (n = 73). INTERVENTIONS: A nonintubated general anesthetic
      technique with spontaneous ventilation via a supraglottic airway device was used
      for minor VATS procedures. This was compared with a case-matched intubated group.
      MEASUREMENTS AND MAIN RESULTS: Both groups had comparable baseline
      characteristics and surgical procedures. The anesthetic time was shorter in the
      nonintubated group (13.6+/-8.3 v 24.1+/-10.9 minutes, p<0.001). Surgical
      operating time and feasibility were similar. Intraoperatively, there were
      increases in end-tidal carbon dioxide (59.1+/-12.9 v 41.8+/-4.6, p<0.001) and
      respiratory rate (17.8+/-5.6 v 13.5+/-2.0, p<0.001) in the nonintubated group.
      Fewer patients in the nonintubated group had moderate-severe pain during recovery
      (19.4% v 48.4%, p = 0.02) and pain on discharge to the ward (25.8% v 61.3%, p =
      0.004). There was a trend toward shorter recovery times, reduced oxygen
      requirement, and shorter hospital stays in the nonintubated group. CONCLUSIONS: A
      nonintubated general anesthetic technique is a feasible alternative to intubated
      general anesthesia for minor VATS procedures.

PMID- 27692904
TI  - Con: Hetastarch Should be Avoided for Volume Expansion in Cardiac Surgery
      Patients.

PMID- 27692902
TI  - DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a
      genome-wide linkage and association study.
AB  - BACKGROUND: Leucine-rich repeat kinase 2 (LRRK2) mutation 6055G->A (Gly2019Ser)
      accounts for roughly 1% of patients with Parkinson's disease in white
      populations, 13-30% in Ashkenazi Jewish populations, and 30-40% in North African
      Arab-Berber populations, although age of onset is variable. Some carriers have
      early-onset parkinsonism, whereas others remain asymptomatic despite advanced
      age. We aimed to use a genome-wide approach to identify genetic variability that
      directly affects LRRK2 Gly2019Ser penetrance. METHODS: Between 2006 and 2012, we
      recruited Arab-Berber patients with Parkinson's disease and their family members
      (aged 18 years or older) at the Mongi Ben Hamida National Institute of Neurology
      (Tunis, Tunisia). Patients with Parkinson's disease were diagnosed by movement
      disorder specialists in accordance with the UK Parkinson's Disease Society Brain
      Bank criteria, without exclusion of familial parkinsonism. LRRK2 carrier status
      was confirmed by Sanger sequencing or TaqMan SNP assays-on-demand. We did genome
      wide linkage analysis using data from multi-incident Arab-Berber families with
      Parkinson's disease and LRRK2 Gly2019Ser (with both affected and unaffected
      family members). We assessed Parkinson's disease age of onset both as a
      categorical variable (dichotomised by median onset) and as a quantitative trait.
      We used data from another cohort of unrelated Tunisian LRRK2 Gly2019Ser carriers
      for subsequent locus-specific genotyping and association analyses. Whole-genome
      sequencing in a subset of 14 unrelated Arab-Berber individuals who were LRRK2
      Gly2019Ser carriers (seven with early-onset disease and seven elderly unaffected
      individuals) subsequently informed imputation and haplotype analyses. We
      replicated the findings in separate series of LRRK2 Gly2019Ser carriers
      originating from Algeria, France, Norway, and North America. We also investigated
      associations between genotype, gene, and protein expression in human striatal
      tissues and murine LRRK2 Gly2019Ser cortical neurons. FINDINGS: Using data from
      41 multi-incident Arab-Berber families with Parkinson's disease and LRRK2
      Gly2019Ser (150 patients and 103 unaffected family members), we identified
      significant linkage on chromosome 1q23.3 to 1q24.3 (non-parametric logarithm of
      odds score 2.9, model-based logarithm of odds score 4.99, theta=0 at D1S2768). In
      a cohort of unrelated Arab-Berber LRRK2 Gly2019Ser carriers, subsequent
      association mapping within the linkage region suggested genetic variability
      within DNM3 as an age-of-onset modifier of disease (n=232; rs2421947; haplotype
      p=1.07 * 10-7). We found that DNM3 rs2421947 was a haplotype tag for which the
      median onset of LRRK2 parkinsonism in GG carriers was 12.5 years younger than
      that of CC carriers (Arab-Berber cohort, hazard ratio [HR] 1.89, 95% CI 1.20
      2.98). Replication analyses in separate series from Algeria, France, Norway, and
      North America (n=263) supported this finding (meta-analysis HR 1.61, 95% CI 1.15
      2.27, p=0.02). In human striatum, DNM3 expression varied as a function of
      rs2421947 genotype, and dynamin-3 localisation was perturbed in murine LRRK2
      Gly2019Ser cortical neurons. INTERPRETATION: Genetic variability in DNM3 modifies
      age of onset for LRRK2 Gly2019Ser parkinsonism and informs disease-relevant
      translational neuroscience. Our results could be useful in genetic counselling
      for carriers of this mutation and in clinical trial design. FUNDING: The Canada
      Excellence Research Chairs (CERC), Leading Edge Endowment Fund (LEEF), Don Rix BC
      Leadership Chair in Genetic Medicine, National Institute on Aging, National
      Institute of Neurological Disorders and Stroke, the Michael J Fox Foundation,
      Mayo Foundation, the Roger de Spoelberch Foundation, and GlaxoSmithKline.

PMID- 27692905
TI  - Healthcare Reform and the Cardiac Anesthesiologist/Intensivist: Challenges Ahead.

PMID- 27692906
TI  - Ghrelin, leptin, and glycemic control after sleeve gastrectomy versus Roux-en-Y
      gastric bypass-results of a randomized clinical trial.
AB  - BACKGROUND: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) cause
      weight loss and metabolic improvement, but results of published studies are
      contradictory. OBJECTIVES: The aim of this study was to compare the effects of SG
      and RYGB on ghrelin, leptin, and glucose homeostasis in a randomized controlled
      trial. SETTING: University hospital, Poland. METHODS: Seventy-two morbidly obese
      patients were randomly selected to undergo either SG (n = 36) or RYGB (n = 36).
      Fasting ghrelin, leptin, glucose, insulin, C-peptide, glucagon, glycated
      hemoglobin, and homeostasis model assessment of insulin resistance were assessed
      preoperatively and at 1, 6, and 12 months postoperatively. No differences were
      found in anthropometric and biochemical parameters between the study groups at
      baseline. RESULTS: Sixty-nine (95.8%) patients completed the study. Percentage of
      excess weight loss at 12 months was 67.6+/-19.3% after SG and 64.2+/-18.5% after
      RYGB (P>.05). Fasting ghrelin levels decreased 1 month after SG (from 76.8 pmol/L
      to 35.3 pmol/L; P<.05) and remained reduced until 12 months (41.6 pmol/L; P<.05)
      but increased 12 months after RYGB from 74.6 pmol/L to 130.2 pmol/L (P<.05).
      Leptin, glucose, insulin, and C-peptide concentrations and glycated hemoglobin
      and homeostasis model assessment of insulin resistance values decreased
      significantly in both groups during 12 months. CONCLUSIONS: RYGB and SG induce
      comparable weight loss and improvement in metabolism of glucose. Ghrelin levels
      decrease after SG and increase after RYGB, but this difference does not affect
      similar outcomes of these procedures during 1-year follow-up. The contribution of
      ghrelin to weight loss or metabolic benefits after bariatric surgery is not
      straightforward, but rather influenced by multiple factors.

PMID- 27692907
TI  - Changes in self-reported eating patterns after laparoscopic sleeve gastrectomy: a
      pre-post analysis and comparison with conservatively treated patients with
      obesity.
AB  - BACKGROUND: Patients with severe obesity need to adapt to surgically induced
      changes in their eating behaviors to maintain treatment success. OBJECTIVES: This
      study examined the effects of laparoscopic sleeve gastrectomy (LSG) on weight
      loss and on 3 dimensions of eating behavior, namely, cognitive restraint,
      disinhibition, and hunger. Outcomes of the LSG group were compared with a group
      of conservatively treated (CT) patients, who underwent a 1-year multimodal weight
      reduction group program that included dietary advice, physical exercise,
      psychoeducation, cognitive-behavioral therapy, training in Jacobson's progressive
      muscle relaxation, and social group support. SETTING: The study setting was a
      multidisciplinary obesity center located in a university hospital. METHODS: A
      sample of 102 patients with obesity were investigated using the Three-Factor
      Eating Questionnaire before and, on average, 19 (+/-5) months after weight loss
      intervention. Of the 102 patients, 62 (age 45.8+/-10.8 years, 71% females)
      underwent LSG, and 40 patients (age 50.6+/-11.3 years, 77.5% females) underwent
      the CT program. Patients were assigned to either the surgical or the nonsurgical
      intervention group following clinical guidelines and patient preference. RESULTS:
      In the LSG group, total weight loss was 25.9+/-11.0%, excess weight loss was
      52.8+/-24.1%, and body mass index decreased from 51.4+/-8.1 to 38.0+/-7.8 kg/m2.
      In the CT group, total weight loss was 5.4+/-10.6%, excess weight loss was 13.9+/
      27.1%, and body mass index decreased from 40.3+/-6.7 to 38.0+/-7.2 kg/m2.
      Significant improvements in self-reported eating behaviors were observed in both
      groups, that is, an increased cognitive restraint of eating, a decreased
      disinhibition of eating control, and a reduced degree of perceived hunger. In
      contrast, whereas Three-Factor Eating Questionnaire scores before weight loss
      intervention did not differ between groups, LSG patients reported significantly
      greater reductions in disinhibition and hunger than CT patients did after weight
      loss intervention. In both groups, greater weight loss was associated with
      decreased hunger sensations. CONCLUSION: In the second follow-up year, LSG was
      associated with greater weight loss and greater improvements in self-reported
      eating behaviors compared with conservative treatment.

PMID- 27692908
TI  - Endoscopic removal of intrajejunal migrated gastric band.

PMID- 27692909
TI  - Oxalate mediated renal complications after Roux-en-Y gastric bypass: weighing the
      risks versus benefits.

PMID- 27692910
TI  - Would you unblind the patient? A case of incidental T1 N0 R0 GIST in a randomized
      controlled trial of sleeve gastrectomy versus Roux-en-Y gastric bypass for morbid
      obesity.

PMID- 27692911
TI  - Simplified laparoscopic Hill repair for the treatment of symptomatic sliding
      hiatus hernia after bariatric surgery.

PMID- 27692912
TI  - The effect of sleeve gastrectomy on GLP-1 secretion and gastric emptying: a
      prospective study.
AB  - BACKGROUND: Rapid gastric emptying has been proposed to justify the increase in
      glucagon-like polypeptide-1 (GLP-1) after laparoscopic sleeve gastrectomy (LSG).
      OBJECTIVES: To assess gastric emptying changes after LSG and their relationship
      with GLP-1 secretion. SETTING: San Salvatore Hospital general surgery unit,
      University of L'Aquila, Italy. METHODS: 52 patients underwent gastric emptying
      scintigraphy for liquid and solid foods, before and 3 months after LSG. Twenty
      six patients were in the liquid group (L group) and the remaining in the solid
      group (S group). We evaluated the half time of gastric emptying (T1/2) and
      percentage of gastric retention (%GR) at 15, 30, and 60 minutes for liquids and
      at 30, 60, 90, and 120 minutes for solids. GLP-1 plasma concentrations were
      measured in each group before and after LSG and related to %GR. Statistical
      analysis was performed by Chi2 test and Pearson correlation(r). RESULTS: After
      surgery, T1/2 was significantly accelerated: 15.2+/-13 min and 33.5+/-18 min in
      the L group and S group, respectively (P<.05). In both groups, GLP-1 plasma
      concentrations were increased at each blood sampling time: 2.91+/-2.9 pg/mL,
      3.06+/-3.1 pg/mL and 3.21+/-2.6 pg/mL at 15, 30, and 60 minutes, respectively,
      (P<.05) for L group and 2.72+/-1.5 pg/mL, 2.89+/-2.1 pg/mL, 2.93+/-1.8 pg/mL, and
      2.95+/-1.9 pg/mL at 30, 60, 90, and 120 minutes, respectively, (P< .05) for the S
      group. After LSG, GLP-1 and %GR presented a negative linear correlation (r) at
      each blood sampling time in both groups. CONCLUSION: The rapid gastric emptying 3
      months after LSG upregulates the production of GLP-1 in the distal bowel. Further
      studies are needed to confirm these findings.

PMID- 27692913
TI  - Robotic Heller myotomy for achalasia after laparoscopic Roux-en-Y gastric bypass:
      a case report and literature review.

PMID- 27692914
TI  - Early reduction of resting energy expenditure and successful weight loss after
      Roux-en-Y gastric bypass.
AB  - BACKGROUND: Weight loss and body composition changes after Roux-en-Y gastric
      bypass (RYGB) may influence resting energy expenditure (REE). The effect of lower
      REE after the procedure on long-term weight remains to be elucidated. OBJECTIVE:
      To evaluate the effects of RYGB on REE and body composition 6 months after RYGB
      and to find out whether postsurgery REE affects weight at 12 and 18 months
      SETTING: Tertiary referral hospital, southern Brazil METHOD: A prospective study
      involving 30 RYGB patients aged>18 years was performed. Body composition was
      evaluated by X-ray absorptiometry and REE by indirect calorimetry. All patients
      were assessed before RYGB and 6 months postoperatively. Further analysis of
      weight was carried out at 12 and 18 months. RESULTS: Baseline body mass index was
      49+/-9 kg/m2 and mean weight was 128+/-19 kg, half of which comprised fat mass
      (50+/-5%). Baseline mean REE was 2297+/-182 kcal/d. The percent total weight loss
      was 26+/-7%, 32+/-9%, and 34+/-9% at 6, 12, and 18 months, respectively. The
      percent excess weight loss gradually increased from 54 +/- 12% at 6 months, to 67
      +/- 18% at 12 months, and 71 +/- 19% at 18 months. REE was significantly lower at
      follow-up (-405+/-108 kcal/d; P<.001). Furthermore, an inverse correlation
      between REE at 6 months and percent excess weight loss at 18 months (r =-.612; P
      = .035) was observed in the subgroup of patients whose REE decreased>405 kcal/d
      at 6 months. CONCLUSION: Patients undergoing RYGB who had a substantial drop in
      REE at 6 months may exhibit less long-term weight loss.

PMID- 27692915
TI  - American Society for Metabolic and Bariatric Surgery estimation of bariatric
      surgery procedures in 2015 and surgeon workforce in the United States.

PMID- 27692916
TI  - Laparoscopic sleeve gastrectomy in children and adolescents with Prader-Willi
      syndrome: a matched control study.

PMID- 27692918
TI  - Optimal Timing for Elective Early Primary Repair of Tetralogy of Fallot: Analysis
      of Intermediate Term Outcomes.
AB  - BACKGROUND: We have previously demonstrated that early primary repair of
      tetralogy of Fallot with pulmonary stenosis (TOF) can be safely performed without
      increase in hospital resource utilization or compromise to surgical technical
      performance scores (TPS). We sought to identify the optimal timing for elective
      early primary repair of TOF with respect to intermediate-term reintervention.
      METHODS: Retrospective review of all patients with TOF undergoing elective
      primary repair between September 2004 and December 2013 was performed. Patients
      were stratified into reintervention group or no reintervention group.
      Multivariable Cox regression analysis identified independent predictors of
      reintervention. Youden's J-index in receiver operating characteristic analysis
      identified optimal age cutoff predictive of reintervention. Kaplan-Meier analysis
      with the log-rank test compared reintervention rates stratified by age and TPS.
      RESULTS: A total of 129 patients with median (interquartile range) age and weight
      of 78 days (56 to 111) and 5 kg (4.1 to 5.7), respectively, underwent primary
      repair. After a median (interquartile range) follow-up of 2.3 years (0.1 to 4.6),
      18 patients (14%) required a total of 22 reinterventions. Youden's J-index
      revealed significantly lower risk of intermediate-term reintervention when
      repaired after 55 days of age (8% for >55 days old versus 31% for <=55 days of
      age). Multivariable Cox regression identified age 55 days and younger (hazard
      ratio [HR] 4.5, 95% confidence interval [CI] 1.6 to 12.8, p = 0.004), valve
      sparing repair (HR 15.3, 95% CI 1.8 to 128.5, p < 0.001), residual right
      ventricular outflow tract (RVOT) gradient (HR 1.11, 95% CI 1.1 to 1.2, p <
      0.001), and inadequate TPS (HR 21.5, 95% CI 7.4 to 63, p < 0.001) as independent
      predictors of overall intermediate-term reintervention. CONCLUSIONS: Elective
      repair in patients greater than 55 days of age, irrespective of size of the
      patient, can be safely performed without any increase in reintervention rates.
      Both residual peak RVOT gradient and TPS are effective in identifying patients at
      increased risk of reintervention.

PMID- 27692917
TI  - Clinical Significance of Spontaneous Echo Contrast on Extracorporeal Membrane
      Oxygenation.
AB  - BACKGROUND: Spontaneous echo contrast (SEC) is known to be a predisposition to
      thromboembolism and cerebrovascular accident. The aim of this study was to
      investigate the risk factors and the consequences of SEC in patients who were
      placed on venoarterial extracorporeal membrane oxygenation (VA-ECMO) because of
      cardiogenic shock. METHODS: Between January 2011 and December 2014, 98 patients
      underwent the insertion of VA-ECMO because of cardiogenic shock in our
      institution. Transthoracic and transesophageal echocardiography was performed and
      interpreted by National Board of Echocardiography certified cardiologists.
      Patients were divided into 2 groups based on the presence or absence of SEC.
      Clinical data, echocardiographic measurements, and outcomes were compared between
      the 2 groups. RESULTS: Of the 98 patients, 22 patients (22%) had SEC on
      echocardiography. Patients in the SEC group had a lower ejection fraction (8.0%
      versus 29%; p < 0.001), a lower pulsatility index (defined by [systolic blood
      pressure - diastolic blood pressure]/mean blood pressure) while receiving ECMO
      (0.13 +/- 0.14 versus 0.26 +/- 0.22; p = 0.009). The SEC group had a higher rate
      of intracardiac thrombus (46% versus 13%; p = 0.002) and stroke (36% versus 7.9%;
      p = 0.002). On univariate analysis, intracardiac thrombus, SEC, and low
      pulsatility were significant risk factors for the development of stroke. On
      multivariate analysis, SEC was the only independent risk factor for stroke.
      CONCLUSIONS: SEC on VA-ECMO resulted in an increased risk of intracardiac
      thrombus and stroke. Maintaining pulsatility while the patient is on ECMO may
      result in a decreased chance of developing SEC and stroke.

PMID- 27692919
TI  - Correction to Lancet Diabetes Endocrinol 2016; 4: 812-14.

PMID- 27692920
TI  - Twenty Fraction Prostate Radiotherapy with Intra-prostatic Boost: Results of a
      Pilot Study.
AB  - AIMS: For patients with high-risk, locally bulky prostate cancer, an intra
      prostatic boost to tumour volumes (dose-painting) offers a risk-adapted dose
      escalation. We evaluated the feasibility of hypofractionated dose-painting
      radiotherapy and the associated toxicity. The possibility to streamline a
      radiobiologically optimised planning protocol was also investigated. MATERIALS
      AND METHODS: Twenty-eight patients were treated using a dose-painting approach;
      boost volumes were identified with functional magnetic resonance imaging scans.
      The prostate dose outside the boost volume was 60 Gy in 20 fractions, and the
      maximum integrated boost dose was set to 68 Gy, provided that the dose
      constraints to the organs at risk could be fulfilled. Rotational intensity
      modulated radiotherapy was used with daily image guidance and fiducial markers.
      RESULTS: The boost dose was escalated to 68 Gy for 25 patients (median dose 69
      Gy, range 68-70 Gy); for three patients the boost dose was 67 Gy, due to the
      proximity of the urethra and/or the rectum. The mean normal tissue complication
      probability for rectal bleeding was 4.7% (range 3.4-5.8%) and was 3.5% for faecal
      incontinence (range 2.3-5.0%). At a median follow-up of 38 months (range 32-45)
      there was no grade 3 toxicity. Two patients developed grade 2 genitourinary
      toxicity (7.1%) and none developed grade 2 gastrointestinal toxicity. The mean
      prostate-specific antigen (PSA) for 23 patients who had stopped the adjuvant
      hormone therapy with a normal testosterone was 0.27 ng/ml (0.02-0.72) at follow
      up; two patients have suppressed PSA and testosterone after stopping 3 year
      adjuvant hormone and three patients have relapsed (one pelvic node, two PSA only)
      at 36, 12 and 42 months, respectively. CONCLUSIONS: A hypofractionated
      radiotherapy schedule, 60 Gy in 20 fractions with intra-prostatic boost dose of
      68 Gy, can be achieved without exceeding dose constraints for organs at risk.
      Hypofractionated dose-painting escalated radiotherapy has an acceptable safety
      profile. The same planning protocol was used in a phase II single-arm trial
      (BIOPROP20: ClinicalTrials.gov identifier NCT02125175) and will further be used
      in a large phase III randomised trial (PIVOTALboost): patients will be randomised
      standard radiotherapy (60 Gy in 20 fractions) with or without lymph node
      radiotherapy versus dose-painting radiotherapy with or without lymph node
      radiotherapy; the trial will be opened for recruitment in summer 2017.

PMID- 27692921
TI  - [Patient with homozygous sickle cell disease and free flap surgery: Ensuring the
      success of the procedure].
AB  - Sickle cell anaemia is rare in France but frequent in Africa, leading to rigid,
      sickle-like shape red blood cells which bind together blocking microcirculation
      under certain circumstances. The vaso-occlusive crisis is the most frequent
      clinical manifestation especially in case of homozygous disease. Sickle cells
      disease is therefore usually considerated as a contraindication to microsurgery,
      however sometimes, a free flap procedure is mandatory. We here report the case of
      a 47-year-old man suffering with homozygous sickle cell anaemia and needing an
      antebrachial free flap procedure for a tongue reconstruction. The postoperative
      course was unremarkable apart from a delayed healing which is common in this
      particular localization. A review of the litterature allows to list the
      precautions to be taken to ensure a microsurgical procedure with this medical
      background. The preoperative examination has to assess usual sickle cell disease
      comorbidities such as kidney failure, heart failure or pulmonary hypertension.
      All the events leading to either low output syndrome, hypoxia, hypothermia, or a
      stress caused by uncontrolled pain should be avoided per- and postoperatively.
      With an optimum medical care, microsurgery is possible even in patients suffering
      with sickle cells anaemia. This case is rare in France but will become frequent
      in Africa with the improvement of the healthcare system, allowing to give all
      patients the best medical care.

PMID- 27692923
TI  - Genomic Energy Landscapes.
AB  - Energy landscape theory, developed in the context of protein folding, provides,
      to our knowledge, a new perspective on chromosome architecture. We review what
      has been learned concerning the topology and structure of both the interphase and
      mitotic chromosomes from effective energy landscapes constructed using Hi-C data.
      Energy landscape thinking raises new questions about the nonequilibrium dynamics
      of the chromosome and gene regulation.

PMID- 27692924
TI  - An overview on the organic pollution around the Qinghai-Tibet plateau: The
      thought-provoking situation.
AB  - The Qinghai-Tibet Plateau plays an important role in the ecological safety and
      human health of the surroundings due to its unique geographical position and
      function. Therefore, it is necessary to study the pollution status and potential
      risk in this area. This study summarizes the distribution of different organic
      pollutants in biota and environmental media of the Qinghai-Tibet Plateau.
      Moreover, it also pays attention to the potential health risks of these organic
      pollutants. Organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons
      (PAHs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers
      (PBDEs) were the most frequently detected in different matrices. In general, the
      carcinogenic risks of organic pollutants were ranked in the very-low to moderate
      range for both children and adults. The carcinogenic risks of organic pollutants
      in fish, food, and water for children were 1-2 times higher than those for
      adults, while risks of organic pollutants in soil/sediment and in air for
      children were generally 10.6-16.5 and 2.6-2.8 times higher than those for adults,
      respectively. The maximal hazard quotient for non-carcinogenic risk was 0.95
      (potential risk for children posed by organic pollutants in yak milk of
      Ruoergai), almost reaching an unacceptable level. Therefore, the potential health
      risks could not be neglected, especially for children who were more likely to be
      affected by the pollutants.

PMID- 27692926
TI  - Differential health effects of short-term exposure to source-specific particles
      in London, U.K.
AB  - BACKGROUND: There is ample evidence of adverse associations between short-term
      exposure to ambient particle mass concentrations and health but little is known
      about the relative contribution from various sources. METHODS: We used air
      particle composition and number networks in London between 2011 and 2012 to
      derive six source-related factors for PM10 and four factors for size
      distributions of ultrafine particles (NSD). We assessed the associations of these
      factors, at pre-specified lags, with daily total, cardiovascular (CVD) and
      respiratory mortality and hospitalizations using Poisson regression. Relative
      risks and 95% confidence intervals (CI) were expressed as percentage change per
      interquartile range increment in source-factor mass or number concentration. We
      evaluated the sensitivity of associations to adjustment for multiple other
      factors and by season. RESULTS: We found no evidence of associations between PM10
      or NSD source-related factors and daily mortality, as the direction of the
      estimates were variable with 95% CI spanning 0%. Traffic-related PM10 and NSD
      displayed consistent associations with CVD admissions aged 15-64years (1.01%
      (95%CI: 0.03%, 2.00%) and 1.04% (95%CI: -0.62%, 2.72%) respectively) as did
      particles from background urban sources (0.36% for PM10 and 0.81% for NSD). Most
      sources were positively associated with pediatric (0-14years) respiratory
      hospitalizations, with stronger evidence for fuel oil PM10 (3.43%, 95%CI: 1.26%,
      5.65%). Our results did not suggest associations with cardiovascular admissions
      in 65+ or respiratory admissions in 15+ age groups. Effect estimates were
      generally robust to adjustment for other factors and by season. CONCLUSIONS: Our
      findings are broadly consistent with the growing evidence of the toxicity of
      traffic and combustion particles, particularly in relation to respiratory
      morbidity in children and cardiovascular morbidity in younger adults.

PMID- 27692927
TI  - Effects of Theta Burst Stimulation on Suprahyoid Motor Cortex Excitability in
      Healthy Subjects.
AB  - BACKGROUND: Continuous theta burst stimulation (cTBS) and intermittent TBS (iTBS)
      are powerful patterns of repetitive transcranial magnetic stimulation (rTMS),
      with substantial potential for motor function rehabilitation post-stroke.
      However, TBS of suprahyoid motor cortex excitability has not been investigated.
      This study investigated TBS effects on suprahyoid motor cortex excitability and
      its potential mechanisms in healthy subjects. METHODS: Thirty-five healthy
      subjects (23 females; mean age = 21.66 +/- 1.66 years) completed three TBS
      protocols on separate days, separated by at least one week. A stereotaxic
      neuronavigation system facilitated accurate TMS positioning. Left and right
      suprahyoid motor evoked potentials (SMEP) were recorded using single-pulse TMS
      from the contralateral suprahyoid motor cortex before stimulation (baseline) and
      0, 15, and 30 min after stimulation. The SMEP latency and amplitude were analyzed
      via repeated measures analysis of variance. RESULTS: cTBS suppressed ipsilateral
      suprahyoid motor cortex excitability and activated the contralateral suprahyoid
      motor cortex. iTBS facilitated ipsilateral suprahyoid motor cortex excitability;
      however, it did not affect the contralateral excitability. iTBS eliminated the
      inhibitory effect caused by cTBS applied to the contralateral suprahyoid motor
      cortex. TBS had no significant effect on the latencies of bilateral SMEP. TBS
      effects on suprahyoid motor cortex excitability lasted a minimum of 30 min.
      CONCLUSIONS: TBS effectively regulates suprahyoid motor cortex excitability.
      Suppression of excitability in one hemisphere leads to further activation of the
      corresponding contralateral motor cortex. iTBS reverses the inhibitory effect
      induced by cTBS of the contralateral suprahyoid motor cortex.

PMID- 27692925
TI  - Behavioral difficulties in 7-year old children in relation to developmental
      exposure to perfluorinated alkyl substances.
AB  - BACKGROUND: Perfluorinated alkyl substances (PFAS) are suspected endocrine
      disruptors that are highly persistent and neurotoxic in animals. Human
      epidemiological studies of exposure-related deviations of children's behaviors
      are sparse. We assessed the associations between prenatal, 5- and 7-year PFAS
      exposures and behavioral problem scores in 7-year Faroese children. METHODS:
      Concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA),
      and perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS), and
      perfluorohexane sulfonic acid (PFHxS) were measured in maternal serum and in
      serum from children at ages 5 and 7years (n=539, 508, and 491, respectively). We
      used multivariable regressions and structural equations models to estimate the
      covariate-adjusted associations between serum-PFAS concentrations and behavioral
      difficulties, as assessed by the strengths and difficulties questionnaire (SDQ)
      at age 7. RESULTS: Serum-PFOS and PFHxS concentrations declined over time,
      whereas PFOA, PFNA, and PFDA tended to increase. No associations were observed
      between prenatal PFAS concentrations and SDQ scores. However, a two-fold increase
      in 5-year serum-PFOA, PFNA, and PFDA concentrations was associated with increases
      in total SDQ scores by 1.03 (95% CI: 0.11, 1.95), 0.72 (95% CI: 0.07, 1.38) and
      0.78 points (95% CI: 0.01, 1.55), respectively. For SDQ subscales, significant
      associations were found in regard to hyperactivity, peer relationship, and
      conduct problems, as well as internalizing and externalizing problems and autism
      screening composite scores. Cross-sectional analyses at age 7years showed
      possible sex-dimorphic associations between PFAS concentrations and SDQ scores,
      where girls had consistently positive associations with SDQ scores whereas boys
      exhibited a pattern of negative or null associations. CONCLUSIONS: Higher serum
      PFAS concentrations at ages 5- and 7-years, but not prenatally, were associated
      with parent-reported behavioral problems at age 7.

PMID- 27692929
TI  - Obama's respiratory health legacy.

PMID- 27692928
TI  - Variability in Response to Quadripulse Stimulation of the Motor Cortex.
AB  - BACKGROUND: Responses to plasticity-inducing brain stimulation protocols are
      highly variable. However, no data are available concerning the variability of
      responses to quadripulse stimulation (QPS). OBJECTIVE: We assessed the QPS
      parameters of motor cortical plasticity induction in a systematic manner, and
      later investigated the variability of QPS using optimal parameters. METHODS:
      First, two different interburst intervals (IBI) with the same total number of
      pulses were compared. Next we investigated three different IBIs with a different
      total number of pulses but with same duration of intervention. We also compared
      the after-effects of monophasic and biphasic QPS. Finally, variability of QPS was
      tested in 35 healthy subjects. Twenty motor evoked potentials (MEPs) were
      measured every 5-10 min for up to one hour after intervention. RESULTS: QPS at an
      IBI of 5 s produced MEPs changes that are dependent on the interstimulus interval
      of the four magnetic pulses, consistent with previous reports. Unexpectedly, QPS
      at an IBI of 2.5 s did not induce any plasticity, even with the same total number
      of pulses, that is, 1440. QPS at an IBI of 7.5 s produced a variable response but
      was likely to be comparable to conventional QPS. Biphasic QPS had shorter lasting
      after-effects compared with monophasic QPS. Finally, the after-effects of QPS
      were relatively consistent across subjects: more than 80% of subjects responded
      as expected in the excitatory QPS at an IBI of 5 s. CONCLUSIONS: The IBI, total
      duration of the procedure and pulse waveform strongly affected the magnitude or
      duration of the plasticity induced by QPS. In this cohort, 80% of subjects
      responded to excitatory QPS as expected.

PMID- 27692930
TI  - Corrections.

PMID- 27692932
TI  - Who receives oral nutritional supplements in nursing homes? Results from the
      nutritionDay project.
AB  - BACKGROUND & AIMS: Oral nutritional supplements (ONS) can be helpful for nursing
      home (NH) residents to prevent or treat malnutrition. Presently little is known
      about the use of ONS in NHs and the factors associated with its use. Thus, the
      aim of this analysis was to describe the use of ONS in NHs participating in the
      nutritionDay project and to determine characteristics of NH residents receiving
      ONS. METHODS: Data from nutritionDay (nD), a cross-sectional multicenter study
      with standardized questionnaires on resident and NH level were analyzed. NH
      residents participating between 2007 and 2014 aged 65 years or older were
      included. Unit characteristics (2 variables), general residents' characteristics
      (18), residents' nutritional status (3) and residents' nutrition (4) were of
      interest as potential predictors of the use of ONS (no vs yes). Univariate binary
      logistic regression (LR) analyses were performed for all variables, and
      significant predictors (p < 0.05) subsequently included in a multivariate
      analysis (backwards LR). RESULTS: 13.9% of 23,689 NH residents received ONS.
      Univariate analysis identified all variables as predictors. After multivariate
      analysis 19 variables remained in the model (Nagelkerke's R2 = 0.319). Odds
      ratios (OR [95% Confidence Interval]) of receiving ONS were highest in residents
      receiving supplementary parenteral nutrition (29.05 [14.85-56.81]; however only
      1.1% of all participants) and fortified diet (11.91 [8.52-16.64]; 5.7%). The odds
      ratio of receiving ONS was 3.26 ([2.86-3.71]; 18.3%) for residents being
      classified as at risk of malnutrition and 4.56 ([3.86-5.40]; 10.0%) for
      malnourished residents according to NH staff. Low BMI and weight loss in the last
      year increased the odds of receiving ONS by 2.34 ([1.93-2.84]; 16.0%) and 1.38
      ([1.23-1.54]; 32.8%), respectively. Furthermore, increasing age, cognitive and
      functional impairment, low food intake on nD, neurological disease and cancer
      were associated with an increased likelihood of the use of ONS. In NH units with
      a nutritional expert (67.1%) and units performing a nutritional assessment at
      least once a month (71.6%), the odds of receiving ONS were also significantly
      increased (1.89 [1.71-2.10] and 1.17 [1.06-1.29]). CONCLUSION: In NHs who
      participated in the nutritionDay, ONS are used for residents with poor
      nutritional and functional status and often in combination with other nutritional
      interventions. Future studies need to clarify the role of NH staff in the
      prescription and distribution of ONS and focus on the reasons for and adequacy of
      the use of ONS in NHs.

PMID- 27692931
TI  - Heart failure and anemia: Effects on prognostic variables.
AB  - BACKGROUND: Anemia is frequent in heart failure (HF), and it is associated with
      higher mortality. The predictive power of established HF prognostic parameters in
      anemic HF patients is unknown. METHODS: Clinical, laboratory, echocardiographic
      and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients
      grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and
      648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for
      males), normal (12-15 for females, 13-15 for males) and high (>15) Hb,
      respectively. RESULTS: Median follow-up was 1363days (606-1883). CPETs were
      always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864).
      No prognostic difference was observed between normal and high Hb groups. Peak
      oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), plasma sodium
      concentration, ejection fraction (LVEF), kidney function and Hb were
      independently related to prognosis in the entire population. Considering Hb
      groups separately, peakVO2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb
      HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692,
      normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High
      VE/VCO2 slope was associated with poor prognosis only in patients with low and
      normal Hb. CONCLUSIONS: Anemic HF patients have a worse prognosis, but CPET can
      be safely performed. PeakVO2 and LVEF, but not VE/VCO2 slope, maintain their
      prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a
      multiparametric approach in HF patients with low Hb. However, the prognostic
      effect of an anemia-oriented follow-up is unknown.

PMID- 27692934
TI  - Endotracheal intubation during manual inline cervical stabilization performed by
      nurses.

PMID- 27692933
TI  - Characterization of oxycodone in vitro metabolism by human cytochromes P450 and
      UDP-glucuronosyltransferases.
AB  - The hepatic metabolism of oxycodone by cytochromes P450 (CYP) and the UDP
      glucuronosyltransferases (UGT), the main metabolic enzymes of phase I and phase
      II, respectively, was assessed in vitro. The N-demethylation by CYP3A4/5 and the
      O-demethylation by CYP2D6 in human liver microsomes (HLM) followed Michaelis
      Menten kinetics, with intrinsic clearances of 1.46MUL/min/mg and 0.35MUL/min/mg,
      respectively. Although noroxycodone and oxymorphone mainly contribute to the
      elimination of oxycodone, the simulated total in vivo clearance using in vitro
      phase I metabolism was underestimated. For the first time, metabolism of
      oxycodone by UGT was deeply investigated using HLM, recombinant enzymes and
      selective inhibitors. Oxycodone-glucuronide was mainly produced by UGT2B7
      (Km=762+/-153MUM, Vmax=344+/-20 peak area/min/mg) and to a lesser extent by
      UGT2B4 (Km=2454+/-497MUM, Vmax=201+/-19 peak area/min/mg). Finally, the kinetics
      of the drug-drug interactions were assessed using two CYP and UGT cocktail
      approaches. Incubations of HLM with phase I and phase II drug probes showed that
      oxycodone mainly decreased the in vitro activities of CYP2D6, CYP3A4/5, UGT1A3,
      UGT1A6 and UGT2B subfamily with an important impact on UGT2B7.

PMID- 27692935
TI  - Neurodevelopmental outcomes and nutritional strategies in very low birth weight
      infants.
AB  - The developing brain of the very low birth weight (VLBW) infant is highly
      sensitive to effects of the nutritional milieu during the neonatal
      hospitalization and after discharge. Strategies to optimize nutritional care play
      an important role in reducing long-term neurodevelopmental morbidities in this
      population. Currently available interventions to ensure that the unique nutrient
      requirements of the VLBW infant are met include various dietary fortification
      strategies and parenteral nutrition. In this article, we review evidence
      regarding nutritional strategies and their beneficial effects on neurodevelopment
      in VLBW infants. We also highlight gaps in current knowledge and areas of current
      investigation that hold promise for improving nutritional care and long-term
      outcomes.

PMID- 27692936
TI  - Acacia shrubs respond positively to high severity wildfire: Implications for
      conservation and fuel hazard management.
AB  - High severity wildfires pose threats to human assets, but are also perceived to
      impact vegetation communities because a small number of species may become
      dominant immediately after fire. However there are considerable gaps in our
      knowledge about species-specific responses of plants to different fire
      severities, and how this influences fuel hazard in the short and long-term. Here
      we conduct a floristic survey at sites before and two years after a wildfire of
      unprecedented size and severity in the Warrumbungle National Park (Australia) to
      explore relationships between post-fire growth of a fire responsive shrub genera
      (Acacia), total mid-story vegetation cover, fire severity and fuel hazard. We
      then survey 129 plots surrounding the park to assess relationships between mid
      story vegetation cover and time-since-fire. Acacia species richness and cover
      were 2.3 and 4.3 times greater at plots after than before the fire. However the
      same common dominant species were present throughout the study. Mid-story
      vegetation cover was 1.5 times greater after than before the wildfire, and Acacia
      species contribution to mid-story cover increased from 10 to 40%. Acacia species
      richness was not affected by fire severity, however strong positive associations
      were observed between Acacia and total mid-story vegetation cover and severity.
      Our analysis of mid-story vegetation recovery showed that cover was similarly
      high between 2 and 30years post-fire, then decreased until 52years. Collectively,
      our results suggest that Acacia species are extremely resilient to high severity
      wildfire and drive short to mid-term increases in fuel hazard. Our results are
      discussed in relation to fire regime management from the twin perspectives of
      conserving biodiversity and mitigating human losses due to wildfire.

PMID- 27692937
TI  - Effects of slope exposure on soil physico-chemical and microbiological properties
      along an altitudinal climosequence in the Italian Alps.
AB  - Due to their sensitivity to changing environmental conditions sub- and alpine
      soils are often monitored in the context of climate change, usually, however,
      neglecting slope exposure. Therefore, we set up a climosequence-approach to study
      the effect of exposure and, in general, climate, on the microbial biomass and
      microbial diversity and activity, comprising five pairs of north (N)- and south
      (S)-facing sites along an altitudinal gradient ranging from 1200 to 2400m a.s.l.
      in the Italian Alps (Trentino Alto Adige, Italy). Soil physico-chemical
      properties were related to microbiological properties (microbial biomass: double
      strand DNA yield vs. substrate-induced respiration; diversity of bacterial,
      fungal and archaeal communities: genetic fingerprinting DGGE vs. real-time PCR;
      microbial activity: basal respiration vs. multiple hydrolytic enzyme assays) to
      monitor shifts in the diversity and activity of microbial communities as a
      function of slope exposure and to evaluate the most determinant chemical
      parameters shaping the soil microbiota. The exposure-effect on several hydrolytic
      key-enzymes was enzyme-specific: e.g. acid phosphomonoesterase potential activity
      was more pronounced at the N-facing slope while the activities of alkaline
      phosphomonoesterase, pyrophosphate-phosphodiesterase and arylsulfatase were
      higher at the S-facing slope. Furthermore, this exposure-effect was domain
      specific: bacteria (S>N, altitude-independent); fungi (N~S); and archaea (N>S;
      altitude-dependent). Additionally, the abiotic parameters shaping the community
      composition were in general depending on soil depth. Our multidisciplinary
      approach allowed us to survey the exposure and altitudinal effects on soil
      physico-chemical and microbiological properties and thus unravel the complex
      multiple edaphic factor-effects on soil microbiota in mountain ecosystems.

PMID- 27692938
TI  - False positive and false negative errors in the design and implementation of agri
      environmental policies: A case study on water quality and agricultural nutrients.
AB  - When designing and implementing agri-environmental policies to reduce nutrient
      loss, action programmes may falsely address areas where the nutrient issue from
      agricultural activity is not currently important and is not likely to become so
      in the future (a false positive), or may fail to address areas where the
      agricultural nutrient issue is currently important or may likely become so in the
      future (a false negative). Based on a case study of the Louros watershed in
      Greece, this work identifies database and modelling sources of false positives
      and negatives and proposes a decision making process aimed at minimizing the
      possibility of committing such errors. The baseline is well simulated and shows
      that the Louro's watershed falls behind a Good Environmental Status, at least
      marginally. Simulated mitigation measures show that the river's status can be
      upgraded to "Good", at least as concerns nitrates and ammonium. Simulated climate
      change does not seem to exert an important positive or negative effect. Land use
      changes forecasting considerably less cultivated area have a significant effect
      on Total Phosphorous but not on nitrates or ammonium concentrations. The non
      linearity between nutrient disposition (inputs) and nutrient concentration in
      downstream water bodies (output) and the many factors that affect the nutrient
      disposition-transportation-concentration chain, highlights the importance of
      simulating the effects of mitigation actions and of future climate and land use
      changes before adopting and establishing agri-environmental measures.

PMID- 27692939
TI  - Detection of Legionella-contaminated aerosols in the vicinity of a bio-trickling
      filter of a breeding sow facility - A pilot study.
AB  - The urbanization of agricultural areas results in a reduction of distances
      between residential buildings and livestock farms. In the public debate,
      livestock farming is increasingly criticized due to environmental disturbance and
      odor nuisance originating from such facilities. One method to reduce odor and
      ammonia is by exhaust air treatment, for example, by biological exhaust air
      purification processes with bio-trickling filters filled with tap water. Higher
      temperatures in the summer time and the generation of biofilms are ideal growth
      conditions for Legionella. However, there are no studies on the presence of
      Legionella in the water of bio-trickling filters and the release of Legionella
      containing aerosols. Therefore, the aim of this study was to investigate
      Legionella in wash water and emitted bioaerosols of a bio-trickling filter system
      of a breeding sow facility. For this purpose, measurements were carried out using
      a cyclone sampler. In addition, samples of wash water were taken. Legionella were
      not found by culture methods. However, using molecular biological methods,
      Legionella spp. could be detected in wash water as well as in bioaerosol samples.
      With antibody-based methods, Legionella pneumophila were identified. Further
      studies are needed to investigate the environmental health relevance of
      Legionella-containing aerosols emitted by such exhaust air purification systems.

PMID- 27692940
TI  - The role of seasonal and hydrological conditions in regulating dissolved
      inorganic nitrogen budgets in a forested catchment in SW Slovenia.
AB  - During two consecutive years the monitoring of rainfall nitrate (NO3-) and
      ammonium (NH4+) concentrations, combined with high-frequency measurements of
      streamwater NO3- concentrations, provided insight into the mechanisms controlling
      the dissolved inorganic nitrogen (DIN) budgets of the forested Padez stream
      catchment in SW Slovenia. During both years, the catchment's annual wet
      atmospheric DIN deposition (12.6 and 13.8kg-N/ha) exceeded the annual DIN export
      (10.7kg-N/ha and 8.8kg-N/ha). The analysis of the monthly DIN budgets discloses
      seasonal patterns. In winter and early spring, the catchment behaves as a net
      source of DIN, whereas during late spring, summer, and early fall the catchment
      generally behaves as a net sink of the atmospheric DIN. Due to large
      evapotranspiration in the growth period, most of the DIN remains in the catchment
      and is flushed during the dormant season. Despite high evapotranspiration and
      consequently low runoff coefficients characteristic for the Mediterranean
      climate, large rainfall events in the growth period can cause intensive washout
      of DIN from the catchment. At a monthly basis, the DIN flushing might exceed the
      catchment's DIN retention capacity and the catchment might behave as a net source
      of DIN. Therefore, the hydrological conditions have the ability to shift the
      catchment's role in regulating the DIN budgets. The high responsiveness of the
      streamwater NO3- concentration in the growth period indicates a large pool of DIN
      in the forest soils which can become mobile by runoff formation. Wet atmospheric
      DIN deposition at the Padez catchment is considerable; highest DIN inputs can be
      expected when air masses approach the catchment from the southwest to southeast
      where there are extensive urban areas along the Italian, Slovenian and Croatian
      coast. However, the Padez catchment does not appear to be approaching N
      saturation, presumably due to strong internal N cycle in the forest soils.

PMID- 27692941
TI  - Transport of sulfacetamide and levofloxacin in granular porous media under
      various conditions: Experimental observations and model simulations.
AB  - Understanding the fate and transport of antibiotics in porous media can help
      reduce their contamination risks to soil and groundwater systems. In this work,
      batch and column experiments were conducted to determine the interactions between
      two representative antibiotics, sulfacetamide (SA) and levofloxacin (LEV), and
      sand porous media under various solution pH, humic acid (HA) concentration, grain
      size, and moisture content conditions. Batch sorption experimental results
      indicated that the sand had relatively strong bonding affinity to LEV, but little
      sorption of SA under different pH, HA concentration, grain size conditions.
      Results from the packed sand column experiments showed that SA had extremely high
      mobility in the porous media for all combinations of pH, HA concentration, grain
      size, and moisture content. The mass recovery of SA was higher than 98.5% in all
      the columns with the exception of the one packed with fine sand (97.2%). The
      retention of LEV in the columns was much higher and the recovery rates ranged
      from 0% to 71.1%. Decreases in solution pH, HA concentration, grain size, or
      moisture content reduced the mobility of LEV in the columns under the tested
      conditions. These results indicated that type of antibiotics and environmental
      conditions also played an important role in controlling their fate and transport
      in porous media. Mathematical models were applied to simulate and interpret
      experimental data, and model simulations described the interactions between the
      two antibiotics and sand porous media very well. Findings from this study
      elucidated the key factors and processes controlling the fate of SA and LEV in
      porous media, which can inform the prediction and assessment of the environmental
      risks of antibiotics.

PMID- 27692942
TI  - Anti-parasite treatment, but not mercury burdens, influence nesting propensity
      dependent on arrival time or body condition in a marine bird.
AB  - Arctic wildlife can be exposed to high mercury (Hg) levels, and are also
      naturally exposed to gastrointestinal parasites that can reduce condition and
      negatively affect reproductive output and/or survival in similar ways.
      Importantly, both Hg and parasites are increasing in wildlife in some Arctic
      regions. We studied the northern common eider duck (Somateria mollissima) to
      explore how Hg in association with both natural levels and experimentally reduced
      parasitic infections, affect reproduction and survival. Female eiders were
      measured, banded, and blood sampled to determine blood Hg burdens, prior to
      breeding. Propensity to nest, clutch size, nest survival, nest attendance, and
      return rates were assessed in relation to both Hg burden and parasite treatment.
      Neither reproduction nor return rates of females varied with Hg concentrations,
      but females arriving late to the colony, or in low body condition, showed
      increased nesting propensity when given the anti-parasite treatment as compared
      to placebo treatment. Our results suggest that parasites can play a critical role
      in decisions to invest in avian breeding annually, particularly among individuals
      with a late onset to breeding, and in poor condition.

PMID- 27692943
TI  - Vitamin D status may help explain racial disparities in breast cancer
      hospitalization outcomes.

PMID- 27692944
TI  - Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for a
      patient presenting with a PRKAG2 mutation.
AB  - OBJECTIVE: PRKAG2 syndrome, an autosomal dominant disorder, is characterized by
      severe infantile hypertrophic cardiomyopathy and heart rhythm disturbances to
      cases with a later presentation and a spectrum of manifestations including
      cardiac manifestations, myopathy and seizures. The cardiac features of PRKAG2
      resemble the cardiac manifestations of Pompe disease. We present a patient who
      was initially diagnosed with Pompe disease and treated with alglucosidase-alfa
      enzyme replacement therapy (ERT); however, he was eventually diagnosed to
      carrying a PRKAG2 pathogenic gene mutation; he did not have Pompe disease instead
      he was a carrier for the common adult leaky splice site mutation in the GAA gene.
      CASE REPORT: At 2.5months, the patient had hypotonia/generalized muscle weakness,
      a diagnosis of non-classic infantile Pompe disease was made based on low acid
      alpha-glucosidase activity and the patient started on ERT at 11months. However,
      1month later, the patient began to have seizures. As the patient's medical
      history was somewhat unusual for infantile Pompe disease, further evaluation was
      initiated and included a glycogen storage disease sequencing panel which showed
      that the patient had a pathogenic mutation in PRKAG2 which had been reported
      previously. ERT was discontinued and patient had a progression of motor deficits.
      ERT was reinitiated by the treating physician, and a clinical benefit was noted.
      CONCLUSION: This report outlines the benefits of ERT with alglucosidase alfa in a
      patient with PRKAG2 syndrome, the decline in his condition when the ERT infusions
      were discontinued, and the significant positive response when ERT was
      reinitiated.

PMID- 27692945
TI  - Reversal of established bone pathology in MPS VII mice following lentiviral
      mediated gene therapy.
AB  - Severe, progressive skeletal dysplasia is a major symptom of multiple
      mucopolysaccharidoses (MPS) types. While a gene therapy approach initiated at
      birth has been shown to prevent the development of bone pathology in different
      animal models of MPS, the capacity to correct developed bone disease is unknown.
      In this study, ex vivo micro-computed tomography was used to demonstrate that
      bone mass and architecture of murine MPS VII L5 vertebrae were within the normal
      range at 1month of age but by 2months of age were significantly different to
      normal. The difference between normal and MPS VII BV/TV increased with age
      reaching a maximal difference at approximately 4months of age. In mature MPS VII
      bone BV/TV is increased (51.5% versus 21.5% in normal mice) due to an increase in
      trabecular number (6.2permm versus 3.8permm in normal mice). The total number of
      osteoclasts in the metaphysis of MPS VII mice was decreased, as was the
      percentage of osteoclasts attached to bone. MPS VII osteoblasts produced
      significantly more osteoprotegerin (OPG) than normal osteoblasts and supported
      the production of fewer osteoclasts from spleen precursor cells than normal
      osteoblasts in a co-culture system. In contrast, the formation of osteoclasts
      from MPS VII spleen monocytes was similar to normal in vitro, when exogenous
      RANKL and m-CSF was added to the culture medium. Administration of murine beta
      glucuronidase to MPS VII mice at 4months of age, when bone disease was fully
      manifested, using lentiviral gene delivery resulted in a doubling of osteoclast
      numbers and a significant increase in attachment capacity (68% versus 29.4% in
      untreated MPS VII animals). Bone mineral volume rapidly decreased by 39% after
      gene therapy and fell within the normal range by 6months of age. Collectively,
      these results indicate that lentiviral-mediated gene therapy is effective in
      reversing established skeletal pathology in murine MPS VII.

PMID- 27692946
TI  - An unusual case of giant coronary sinus causing left ventricular inflow
      obstruction.

PMID- 27692948
TI  - Discussion.

PMID- 27692947
TI  - Assessment of thrombosis in right internal jugular vein after percutaneous
      superior vena cava catheter insertion during cardiovascular surgery with
      cardiopulmonary bypass.
AB  - OBJECTIVE: We evaluated the incidence of percutaneous superior vena cava catheter
      related thrombosis and identified risk factors for developing the condition in
      patients undergoing cardiovascular surgery with cardiopulmonary bypass. METHODS:
      A total of 121 patients were evaluated. A percutaneous superior vena cava
      catheter was inserted into the right internal jugular vein during cardiovascular
      surgery with cardiopulmonary bypass. The right internal jugular vein was
      evaluated using ultrasonography, including cross-sectional area and velocity just
      before insertion of the percutaneous superior vena cava catheter (preoperative)
      and 24 hours and 48 hours after its insertion. If an echogenic mass was detected
      in the right internal jugular vein, the size was measured. RESULTS: The incidence
      of thrombosis in the right internal jugular vein was 56.2%. Change in the right
      internal jugular vein cross-sectional area and velocity had no clinical
      implications. Multiple logistic regression analysis identified age (odds ratio,
      1.061; 95% confidence interval, 1.022-1.101; P = .002), superior vena cava
      catheter indwelling duration (odds ratio, 1.015; 95% confidence interval, 1.008
      1.023; P < .001), and amount of transfusion platelet concentrate (odds ratio,
      1.155; 95% confidence interval, 1.030-1.295; P = .013) as risk factors for
      percutaneous superior vena cava catheter-related thrombosis in the right internal
      jugular vein. CONCLUSIONS: The incidence of percutaneous superior vena cava
      catheter-related thrombosis was higher than conventional central venous catheter
      related thrombosis. Risk factors were age, superior vena cava catheter indwelling
      duration, and amount of transfusion platelet concentrate.

PMID- 27692950
TI  - Changes in United States heart allocation: A community energized to improve
      policy.
AB  - Donor heart allocation in the United States has not evolved in concert with
      changes in the characteristics of patients on the waiting list or evolution in
      technology. Data showing the growing population of patients with advanced heart
      failure coupled with the relatively fixed number of cardiac donors and regional
      access disparities motivated the United Network for Organ Sharing (UNOS) Thoracic
      Committee to reexamine candidate prioritization and broader organ sharing. The
      resultant proposed policy change stratifies patients in a more granular manner
      based primarily on wait-list mortality and is designed to expand the geographic
      boundaries to permit greater access to donor hearts for the most critically ill
      patients awaiting transplant.

PMID- 27692949
TI  - Does moderate hypothermia really carry less bleeding risk than deep hypothermia
      for circulatory arrest? A propensity-matched comparison in hemiarch replacement.
AB  - BACKGROUND: Moderate (MHCA) versus deep (DHCA) hypothermia for circulatory arrest
      in aortic arch surgery has been purported to reduce coagulopathy and bleeding
      complications, although there are limited data supporting this claim. This study
      aimed to compare bleeding-related events after aortic hemiarch replacement with
      MHCA versus DHCA. METHODS: Patients who underwent hemiarch replacement at a
      single institution from July 2005 to August 2014 were stratified into DHCA and
      MHCA groups (minimum systemic temperature <=20 degrees C and >20 degrees C,
      respectively) and compared. Then, 1:1 propensity matching was performed to adjust
      for baseline differences. RESULTS: During the study period, 571 patients
      underwent hemiarch replacement: 401 (70.2%) with DHCA and 170 (29.8%) with MHCA.
      After propensity matching, 155 patients remained in each group. There were no
      significant differences between matched groups with regard to the proportion
      transfused with red blood cells, plasma, platelet concentrates, or
      cryoprecipitate on the operative day, the rate of reoperation for bleeding, or
      postoperative hematologic laboratory values. Among patients who received plasma,
      the median transfusion volume was statistically greater in the DHCA group (6 vs 5
      units, P = .01). MHCA also resulted in a slight reduction in median volume of
      blood returned via cell saver (500 vs 472 mL, P < .01) and 12-hour postoperative
      chest tube output (440 vs 350, P < .01). Thirty-day mortality and morbidity did
      not differ significantly between groups. CONCLUSIONS: MHCA compared with DHCA
      during hermiarch replacement may slightly reduce perioperative blood-loss and
      plasma transfusion requirement, although these differences do not translate into
      reduced reoperation for bleeding or postoperative mortality and morbidity.

PMID- 27692951
TI  - Predictors of survival in adults undergoing extracorporeal membrane oxygenation
      with severe infections.
AB  - BACKGROUND: To identify novel factors associated with the survival of septic
      adults receiving extracorporeal membrane oxygenation (ECMO) to improve patient
      selection and outcomes. METHODS: Cases were identified from our ECMO registry
      from 2001 to 2011 if they were >=16 years and received ECMO for life-threatening
      sepsis. RESULTS: A total of 151 adults with a median (25th-75th percentile) age
      of 51 (37-63) years were analyzed. Pneumonia (50%), myocarditis (20%), and
      primary bloodstream infections (15%) were the main types of infection, caused by
      predominantly nonfermentative Gram-negative bacteria (NFGNB) (26%),
      Enterobacteriaceae (24%), and Gram-positive cocci (21%). The in-hospital
      mortality of patients with NFGNB, enteric, and Gram-positive bacterial pneumonias
      were 100%, 68%, and 14%, respectively. Using the Cox-proportional hazards model,
      we found that age >75 years (hazard ratio [HR], 1.98, 95% confidence interval
      [95% CI], 1.30-3.02), pre-ECMO dialysis (HR, 3.20, 95% CI, 1.34-7.63), longer
      door-to-ECMO intervals (HR, 1.01, 95% CI, 1.00-1.02), venoarterial mode (HR,
      2.58, 95% CI, 1.55-4.21), and fungal (HR, 2.83, 95% CI, 1.36-5.88) and NFGNB
      sepsis (HR, 2.48, 95% CI, 1.44-4.27) were associated with mortality. Gram
      positive sepsis (HR, 0.20, 95% CI, 0.08-0.57), myocarditis (HR, 0.12, 95% CI,
      0.06-0.27), pneumonia (HR, 0.54, 95% CI, 0.30-0.90), and effective empirical
      antimicrobial therapy were predictive of survival (HR, 0.57, 95% CI, 0.37-0.89);
      all P < .05. Excluding the 67 heavily premorbid patients, we found that 54%
      survived ECMO and 42% survived to discharge, with significantly more survivors
      with door-to-ECMO times of <=96 hours than >96 hours (59% vs 15%, P < .0001).
      CONCLUSIONS: Better outcomes were associated with door-to ECMO times of 96 hours
      or less, for Gram-positive rather than Gram-negative sepsis, and for pneumonia
      rather than primary bloodstream infections.

PMID- 27692953
TI  - Discussion.

PMID- 27692952
TI  - Left ventricular assist device as destination therapy in cardiac end-stage
      dystrophinopathies: Midterm results.
AB  - OBJECTIVE: We report our experience with the use of a left ventricular assist
      device (LVAD) as destination therapy (DT) for the management of patients with
      cardiac end-stage dystrophinopathies. METHODS: From February 2011 to February
      2016, 7 patients with dystrophinopathies and dilated cardiomyopathy (DCM) were
      treated with LVADs at our institution. Median age at surgery was 16.5 years
      (range, 14.2-23.4 years). All patients were preoperatively evaluated by a
      multidisciplinary team approach. RESULTS: All patients survived to hospital
      discharge. The early postoperative course was characterized by abdominal bleeding
      (1 patient) and retropharyngeal bleeding (1 patient). Because of abdominal or
      retropharyngeal bleeding, both required postoperative heparin infusion
      discontinuation for 35 and 33 days, respectively. Among the late complications, 1
      child developed osteolysis and infection at the pedestal site of the device,
      which required surgical displacement; 1 patient required gastrostomy as a result
      of poor feeding, and another had a cerebral stroke, which was treated with
      percutaneous thrombus aspiration. The other 2 patients did not show early or late
      complications. At a median follow-up time of 21.7 months (range, 3-45 months)
      there have been 3 deaths: 1 patient died of a lung infection after 45 months, 1
      died of tracheal bleeding after 29 months, and 1 died of cerebral hemorrhage
      after 14 months. CONCLUSIONS: Our experience indicates that the use of an LVAD as
      DT in patients with dystrophinopathies with end-stage DCM is feasible, suggesting
      that it may be suitable as a palliative therapy for the treatment of these
      patients with no other therapeutic options.

PMID- 27692954
TI  - Tissue engineering of the heart: An evolving paradigm.
AB  - Tissue-engineered regeneration of a failing human heart remains a major
      challenge, while cardiovascular disease continues to take more lives than all
      cancers combined. Much has been learned from the basic and clinical studies, with
      the most interesting developments happening at the interfaces of disciplines.
      This seems to be the right time to step back and rethink the evolving paradigm of
      tissue engineering, and to reflect about the most promising directions to take.
      We clearly need new therapeutic modalities that are effective and yet simple
      enough to be practical, and the field is looking into the therapeutic potential
      of stem-progenitor cells, cardiac and vascular, that are enabled by bioactive
      factors and functionalized biomaterials.

PMID- 27692955
TI  - Outcome of aortic arch reconstruction in infants with coarctation: Importance of
      operative approach.
AB  - OBJECTIVES: Coarctation with hypoplastic aortic arch can be treated with
      resection and extended end-to-end anastomosis (REEEA) as well as end-to-side
      anastomosis (ESA). The aim of the study was to review our experience with these
      techniques in newborns and infants and to assess mid-term outcome with regards to
      morbidity, mortality, and reintervention rate in relation to operative access and
      technique. PATIENTS AND METHODS: Retrospective review of hospital charts and
      surgical reports from 183 consecutive newborns and infants with coarctation and
      hypoplastic aortic arch with or without ventricular septal defect between 1996
      and 2013. Median age at surgery was 15 days (0-345). Lateral thoracotomy was used
      as operative access in 111 patients; 72 patients had a median sternotomy, 71 of
      them with cardiopulmonary bypass (ESA n = 30, REEEA n = 41). Fifty-two patients
      (28.4%) had an additional ventricular septal defect closure. Follow-up data were
      available for 75.96% with a median follow-up of 6.3 years (0.2-18.16 years).
      RESULTS: Thirty-day mortality was 0.54% with no late mortality occurring during
      follow-up. There was 1 severe complication: paraplegia and cerebral hypoxemia
      after REEEA. Freedom from mortality and reintervention at 10 years was 99.27% and
      90.12%, respectively. Lateral thoracotomy as operative access was a risk factor
      for recurrent obstruction (P = .03). CONCLUSIONS: REEEA and ESA were safe and
      effective treatments in newborns and infants. In borderline cases, aortic arch
      reconstruction should be performed through a median sternotomy on bypass.

PMID- 27692956
TI  - Why doesn't the flow study work better for pulmonary atresia, ventricular septal
      defect, and major aortopulmonary collaterals?

PMID- 27692957
TI  - Twitter as a survey tool for real-time unbiased snapshots of personal sentiment
      in population level.

PMID- 27692958
TI  - Usefulness of T2 ratio in the diagnosis and prognosis of cardiac amyloidosis
      using cardiac MR imaging.
AB  - PURPOSE: To detect if a difference of T2 ratio, defined as the signal intensity
      (SI) of the myocardium divided by the SI of the skeletal muscle on T2-weigthed
      cardiac magnetic resonance (CMR) imaging, exists between patients with systemic
      amyloidosis, by comparison to control subjects. To determine if a relationship
      exists between T2 ratio and the overall mortality. MATERIALS AND METHODS: CMR
      imaging examinations of 73 consecutive patients (48 men, 25 women; mean age, 63
      years+/-15[SD]) with amyloidosis and suspicion of CA and 27 control subjects were
      retrospectively analyzed after institutional review board approval. Final
      diagnosis of CA was retained in case of histological confirmation of CA, typical
      pattern of CA on imaging and/or positivity of 99Technetium-hydroxymethylene
      diphosphonate scintigraphy. Patients were divided in 2 groups according to the
      presence or the absence of CA. T2 ratios were calculated in patients with and
      those without CA and in control subjects with using analysis of variance.
      Prognostic value of T2 ratio was studied with a Kaplan-Meier curve. RESULTS:
      Thirty-five patients (51%) had CA and 33 (49%) were free from CA. T2 ratio was
      lower in patients with CA (1.18+/-0.29) than in patients without cardiac
      involvement (1.37+/-0.35) (P=0.03) and control subjects (1.45+/-0.24) (P=0.004).
      A T2 ratio of 1.36 was the best threshold value for predicting CA with a
      sensitivity of 63% and a specificity of 73%. Kaplan-Meier analysis showed a
      significant relationship between a shortened overall survival and a T2
      ratio<1.36. CONCLUSION: Patients with CA exhibit lower T2 ratio on CMR imaging by
      comparison with patients free of CA and control subjects.

PMID- 27692959
TI  - Sarah's birth. How the medicalisation of childbirth may be shaped in different
      settings: Vignette from a study of routine intervention in Jeddah, Saudi Arabia.
AB  - BACKGROUND: The expansion of the medicalisation of childbirth has been described
      in the literature as being a global phenomenon. The vignette described in this
      paper, selected from an ethnographic study of routine intervention in Saudi
      Arabian hospitals illustrates how the worldwide spread of the bio-medical model
      does not take place within a cultural vacuum. AIM: To illuminate the ways in
      which the medicalisation of birth may be understood and practised in different
      cultural settings, through a vignette of a specific birth, drawn as a typical
      case from an ethnographic study that investigated clinical decision-making in the
      second stage of labour in Saudi Arabia. METHODS: Ethnographic data collection
      methods, including participant observation and interviews. The data presented in
      this paper are drawn from ethnographic field notes collected during field work in
      Saudi Arabia, and informed by analysis of a wider set of field notes and
      interviews with professionals working in this context. FINDINGS: While the
      medicalisation of care is a universal phenomenon, the ways in which the care of
      women is managed using routine medical intervention are framed by the local
      cultural context in which these practices take place. DISCUSSION: The
      ethnographic data presented in this paper shows the medicalisation of birth
      thesis to be incomplete. The evidence presented in this paper illustrates how
      local belief systems are not so much subsumed by the expansion of the bio-medical
      model of childbirth, rather they may actively facilitate a process of localised
      reinterpretation of such universalised and standardised practices. In this case,
      aspects of the social and cultural context of Jeddah operates to intensify the
      biomedical model at the expense of respectful maternity care. CONCLUSION: In this
      article, field note data on the birth of one Saudi Arabian woman is used as an
      illustration of how the medicalisation of childbirth has been appropriated and
      reinterpreted in Jeddah, Saudi Arabia.

PMID- 27692960
TI  - Association between Physical Activity and Health-Related Quality of Life in
      Adults with Type 2 Diabetes.
AB  - OBJECTIVES: To examine the association between meeting physical-activity
      recommendations and health-related quality of life (HRQL) in adults with type 2
      diabetes. METHODS: Data from the Alberta's Caring for Diabetes cohort were used.
      Self-report questionnaires were mailed to patients with type 2 diabetes who were
      living in Alberta, Canada. Weekly moderate-vigorous physical activity (MVPA) was
      reported using the Godin Leisure Time Physical Activity Questionnaire, and HRQL
      was reported using the Medical Outcomes Study (MOS) 12-Item Short-Form Health
      Survey v. 2 (SF-12 v. 2) and the 5-level EuroQol 5-Dimensions (EQ-5D). Based on
      current guidelines for patients with type 2 diabetes in Canada, participants were
      grouped according to whether they accrued 150 minutes of MVPA per week.
      Multivariable linear regression models were used to explore associations between
      physical activity and HRQL. RESULTS: The mean age of participants (N=1948) was
      64.5+/-10.8, and 45% were female. Participants reported a mean of 84.1+/-172.4
      minutes of MVPA per week, and 21% (n=416) met recommendations for physical
      activity. Those who met physical activity recommendations reported higher scores
      on physical functioning (b=9.58; p<0.001); role-physical (b=8.87; p=0.001);
      bodily pain (b=5.12; p=0.001); general health (b=6.66; p<0.001); vitality
      (b=9.05; p<0.001); social functioning (b=3.32; p=0.040); and role-emotional
      (b=3.08; p=0.010); physical component summary (b=3.31; p<0.001); mental component
      summary (b=1.43; p=0.001) and EQ-5D-5L index score (b=0.022; p=0.005) compared to
      those not meeting recommendations. CONCLUSIONS: The majority of the sample did
      not meet the guidelines for physical activity. Among those who did, a significant
      positive association was observed with HRQL, particularly physical health.

PMID- 27692961
TI  - Contrast-Induced Nephropathy After Primary Percutaneous Coronary Intervention:
      The Need for a Unifying Definition.

PMID- 27692962
TI  - Impairing Cohesin Smc1/3 Head Engagement Compensates for the Lack of Eco1
      Function.
AB  - The cohesin ring, which is composed of the Smc1, Smc3, and Scc1 subunits,
      topologically embraces two sister chromatids from S phase until anaphase to
      ensure their precise segregation to the daughter cells. The opening of the ring
      is required for its loading on the chromosomes and unloading by the action of
      Wpl1 protein. Both loading and unloading are dependent on ATP hydrolysis by the
      Smc1 and Smc3 "head" domains, which engage to form two composite ATPase sites.
      Based on the available structures, we modeled the Saccharomyces cerevisiae
      Smc1/Smc3 head heterodimer and discovered that the Smc1/Smc3 interfaces at the
      two ATPase sites differ in the extent of protein contacts and stability after ATP
      hydrolysis. We identified smc1 and smc3 mutations that disrupt one of the
      interfaces and block the Wpl1-mediated release of cohesin from DNA. Thus, we
      provide structural insights into how the cohesin heads engage with each other.

PMID- 27692963
TI  - Dynamically Coupled Residues within the SH2 Domain of FYN Are Key to Unlocking
      Its Activity.
AB  - Src kinase activity is controlled by various mechanisms involving a coordinated
      movement of kinase and regulatory domains. Notwithstanding the extensive
      knowledge related to the backbone dynamics, little is known about the more subtle
      side-chain dynamics within the regulatory domains and their role in the
      activation process. Here, we show through experimental methyl dynamic results and
      predicted changes in side-chain conformational couplings that the SH2 structure
      of Fyn contains a dynamic network capable of propagating binding information. We
      reveal that binding the phosphorylated tail of Fyn perturbs a residue cluster
      near the linker connecting the SH2 and SH3 domains of Fyn, which is known to be
      relevant in the regulation of the activity of Fyn. Biochemical perturbation
      experiments validate that those residues are essential for inhibition of Fyn,
      leading to a gain of function upon mutation. These findings reveal how side-chain
      dynamics may facilitate the allosteric regulation of the different members of the
      Src kinase family.

PMID- 27692964
TI  - The Preserved HTH-Docking Cleft of HIV-1 Integrase Is Functionally Critical.
AB  - HIV-1 integrase (IN) catalyzes viral DNA integration into the host genome and
      facilitates multifunctional steps including virus particle maturation. Competency
      of IN to form multimeric assemblies is functionally critical, presenting an
      approach for anti-HIV strategies. Multimerization of IN depends on interactions
      between the distinct subunit domains and among the flanking protomers. Here, we
      elucidate an overlooked docking cleft of IN core domain that anchors the N
      terminal helix-turn-helix (HTH) motif in a highly preserved and functionally
      critical configuration. Crystallographic structure of IN core domain in complex
      with Fab specifically targeting this cleft reveals a steric overlap that would
      inhibit HTH-docking, C-terminal domain contacts, DNA binding, and subsequent
      multimerization. While Fab inhibits in vitro IN integration activity, in vivo it
      abolishes virus particle production by specifically associating with preprocessed
      IN within Gag-Pol and interfering with early cytosolic Gag/Gag-Pol assemblies.
      The HTH-docking cleft may offer a fresh hotspot for future anti-HIV intervention
      strategies.

PMID- 27692965
TI  - Structural Basis of Interfacial Flexibility in Fibrin Oligomers.
AB  - Fibrin is a filamentous network made in blood to stem bleeding; it forms when
      fibrinogen is converted into fibrin monomers that self-associate into oligomers
      and then to polymers. To gather structural insights into fibrin formation and
      properties, we combined high-resolution atomic force microscopy of fibrin(ogen)
      oligomers and molecular modeling of crystal structures of fibrin(ogen) and its
      fragments. We provided a structural basis for the intermolecular flexibility of
      single-stranded fibrin(ogen) oligomers and identified a hinge region at the D:D
      inter-monomer junction. Following computational reconstruction of the missing
      portions, we recreated the full-atomic structure of double-stranded fibrin
      oligomers that was validated by quantitative comparison with the experimental
      images. We characterized previously unknown intermolecular binding contacts at
      the D:D and D:E:D interfaces, which drive oligomerization and reinforce the intra
      and inter-strand connections in fibrin besides the known knob-hole bonds. The
      atomic models provide valuable insights into the submolecular mechanisms of
      fibrin polymerization.

PMID- 27692967
TI  - Review of head-to-head study designs in rheumatoid arthritis.
AB  - OBJECTIVE: Treatment options available to patients with rheumatoid arthritis (RA)
      are ever-changing, and understanding the similarities and differences of efficacy
      and safety between different RA therapies is of key importance in order to
      facilitate treatment decisions by both the patient and physician. Very few head
      to-head, peer-reviewed trials exist; instead, evidence for efficacy of treatments
      is often ascertained from placebo-controlled trials, registries and meta
      analyses, which often do not sufficiently address the relative effectiveness of
      two medications. METHODS: A targeted review of indirect comparison methods, and
      ongoing and published clinical studies assessing the efficacy and safety, and the
      comparative efficacy and safety of biologic disease modifying antirheumatic drugs
      in RA. RESULTS: Critical elements that should be considered when designing head
      to head trials are described using examples of true head-to-head and placebo
      controlled randomized controlled trials (RCTs). The appropriate use of head-to
      head trial designs is demonstrated by reviewing different examples of well
      designed clinical trials, and an overview is presented of the challenges
      associated with indirect comparisons. This review also examines the use of
      studies comparing therapies to placebo, highlighting the difficulties associated
      with the interpretation of these studies. CONCLUSIONS: For comparative trials to
      contribute to evidence-based decision making in the treatment of RA, patient
      populations and treatment regimens as similar as possible to those used in
      routine clinical practice should be employed and the trial should be
      appropriately designed to answer the specific question asked.

PMID- 27692968
TI  - A geometric morphometric evaluation of the Belanglo 'Angel' facial approximation.
AB  - In August 2011, a 2D facial approximation was undertaken of remains discovered in
      Australia's Belanglo State Forrest; in October 2015, the young woman was
      identified. Referencing three photographs of the young woman as she appeared in
      life and a database of 64 sex, age, head pose and population matched images, the
      facial approximation is evaluated for relative shape accuracy through the
      application of geometric morphometrics. The results are that the facial
      approximation is significantly similar to the images of the young woman in facial
      morphology (p=0.002) when most of the variance due to depicted head pose is
      removed from the analyses. The geometric morphometric analyses, however, also
      highlight the facial approximation's face and feature discrepancies, some of
      which would have likely disrupted familiar face recognition. Although
      predominantly verified methods were applied in 2011, they are limited in their
      predictive accuracy, not every feature of the face has a verified method to
      apply, and practitioner errors as well as photographic distortions are apparent.
      Furthermore, an assumption that the verified methods require inter-feature
      agreement (in this instance eye spacing and mouth width) was proved to be false.
      Overall this study shows that it is possible to assess the morphological accuracy
      of a forensic facial approximation when a number of antemortem images are
      available, though the influence of photographic distortion within 2D photographs
      will always preclude a precise metric assessment.

PMID- 27692966
TI  - Erosive osteoarthritis: A systematic analysis of definitions used in the
      literature.
AB  - BACKGROUND: Erosive osteoarthritis (EOA) is a commonly invoked diagnosis
      representing an important variant of hand osteoarthritis (OA). There is
      increasing literature on the prevalence, risk factors, etiology, and management
      of EOA. METHODS: We systematically reviewed the literature to assess variability
      in the diagnostic definitions used to define EOA in these studies. RESULTS: We
      reviewed 336 articles and found 62 articles citing diagnostic definitions for
      EOA. Radiographic appearance was the most commonly used criterion, but there was
      little agreement on the details or extent of the radiographic changes. Overall,
      56 of the 62 studies included clinical features in the diagnostic definitions,
      yet these features varied considerably. Exclusion criteria were mentioned in 43
      of the studies. CONCLUSION: Based on the widely disparate definitions of EOA, we
      urge caution in interpretation of this literature, and propose that further
      understanding of EOA will require consensus on its definition.

PMID- 27692969
TI  - Quantitative evaluation of pancreatic tumor fibrosis using shear wave
      elastography.
AB  - BACKGROUND & AIMS: There is no established non-invasive method for diagnosis of
      pancreatic fibrosis. Shear wave elastography (SW-EG) may be a candidate for this
      purpose. The aims of this study were to assess the reproducibility of SW-EG in
      the normal imaging pancreas (Phase 1) and to evaluate the diagnostic performance
      of SW-EG for pancreatic fibrosis classified histologically (Phase 2). METHODS:
      Phase 1: This included 127 cases that underwent SW-EG of the normal imaging
      pancreas. SW-EG was measured at least five times in the pancreatic parenchyma and
      the median of repeated measurements was defined as the pancreatic elastic modulus
      (PEM). Phase 2: This included 53 cases that underwent SW-EG of the pancreatic
      parenchyma preoperatively and in which pancreas parenchyma were evaluated
      histologically. Histological fibrosis was graded in 4 stages: normal, mild,
      moderate, and severe. RESULTS: Phase 1: Median PEM in the head, body, and tail of
      the pancreas were 3.23, 3.17, and 2.91 kPa, respectively, with no significant
      difference among regions (P = 0.554). The intraclass correlation coefficient
      showed good reproducibility (rho = 0.71) after 5 measurements. Phase 2: There was
      a significant positive correlation between PEM and the histological pancreatic
      fibrosis stage (rs = 0.63, P < 0.001). Areas under the receiver operating
      characteristic curve for the accuracy of SW-EG for diagnosis of pancreatic
      fibrosis were 0.85 (>=mild), 0.84 (>=moderate), and 0.87 (severe). CONCLUSION: SW
      EG can be used to determine the stage of pancreatic fibrosis non-invasively with
      high accuracy and reproducibility.

PMID- 27692971
TI  - Incidence and Etiology of Sudden Cardiac Arrest and Death in High School Athletes
      in the United States.
AB  - OBJECTIVE: To determine the incidence and etiology of sudden cardiac arrest and
      death (SCA/D) in US high school athletes. PATIENTS AND METHODS: A prospective
      media database of SCA/D was queried for cases aged 14 to 18 years from 7 states
      over 6 school years (September 1, 2007, to August 30, 2013). Event details were
      investigated to determine participation on a high school athletic team, sex,
      sport, and occurrence during school-sponsored activity or exertion. National
      sports participation numbers were used and a conversion factor was applied to
      account for multisport athletes. Autopsy reports were reviewed and cause of death
      was adjudicated by an expert panel. RESULTS: A total of 16,390,409 million
      athlete-seasons representing 6,974,640 athlete-years (AY) were examined,
      encompassing 36% of the total US high school athlete population. A total of 104
      cases of SCA/D were identified (35 SCA with survival and 69 sudden cardiac deaths
      [SCDs]). The rate of SCD was 1:101,082 AY and of SCA/D 1:67,064 AY. Eighty-eight
      percent (92) of events occurred in male athletes. The rate of SCA/D in male
      athletes was 1:44,832 AY and in female athletes 1:237,510 AY (incidence rate
      ratio, 5.3; 95% CI, 2.9-10.6; P<.001). Men's basketball was the highest risk
      sport with an SCA/D incidence of 1:37,087 AY followed by men's football at
      1:86,494 AY. Men's basketball and football athletes accounted for 57% (39) of
      deaths. Eighty percent of SCDs (55 of 69) were exertional and 55% (38 of 69)
      occurred while playing for a school-sponsored team. Autopsy reports were obtained
      in 73% (50) of cases. The most common findings of autopsy were idiopathic left
      ventricular hypertrophy or possible cardiomyopathy (13 of 50 [26%]), autopsy
      negative sudden unexplained death (9 of 50 [18%]), hypertrophic cardiomyopathy (7
      of 50 [14%]), and myocarditis (7 of 50 [14%]). CONCLUSION: The rate of SCA/D in
      male high school athletes was 1:44,832 AY, with almost half due to possible or
      confirmed cardiomyopathy disease. It is likely that many cases were not
      identified because of reliance on media reports, and these numbers represent a
      minimum estimate.

PMID- 27692970
TI  - Increasing Incidence of Melanoma in the Elderly: An Epidemiological Study in
      Olmsted County, Minnesota.
AB  - OBJECTIVE: To estimate the age- and sex-adjusted incidence of melanoma in adults
      61 years or older in Olmsted County, Minnesota, from 1970 through 2009. PATIENTS
      AND METHODS: Using Rochester Epidemiology Project resources, 397 patients were
      identified who were 61 years or older and who received a first lifetime diagnosis
      of melanoma from January 1, 1970, through December 31, 2009, in Olmsted County.
      The incidence of melanoma and the overall and disease-specific survival rates
      were compared by age, sex, year of diagnosis, and stage of disease. RESULTS: From
      1970 through 2009, age- and sex-adjusted incidence increased significantly
      (P<.001) from 17.0 (95% CI, 8.6-25.4) to 124.6 (95% CI, 108.9-140.3) per 100,000
      person-years, with a 4-fold increase in women and a more than 11-fold increase in
      men. In men, incidence rates increased with age (P<.001) and over time (P<.001).
      In women, incidence rates increased over time (P<.001) but were constant across
      all age groups studied (P=.90). The dramatic increase in the incidence of
      melanoma was observed mainly for stages 0 and I tumors in both men and women (>55
      fold increase). Disease-specific survival increased across the decades (P<.001);
      when year of diagnosis was compared to mortality, hazard ratios were 0.94 (95%
      CI, 0.90-0.99; P=.010) and 0.93 (95% CI, 0.89-0.98; P=.006) for men and women,
      respectively. CONCLUSION: The incidence of melanoma in older men and women
      increased significantly over the past 4 decades in Olmsted County, with men
      experiencing higher rates of increase than did women.

PMID- 27692972
TI  - Implementation of a Diabetes Transition of Care Program.
AB  - For adolescents with diabetes, ineffective health care transition to adult health
      services may result in suboptimal adherence to medical supervision, leading to
      poor glycemic control, increased diabetes complications, and hospitalization.
      Despite national recommendations, few youth receive the needed preparation to
      transition to adult health services. A data transition registry was created at a
      large Midwest urban academic medical center to identify patients 14 years and
      older with Type 1 diabetes. Thirty-nine patients with Type 1 diabetes were
      identified, and 33 were eligible to begin transition planning. Baseline
      Transition Readiness Assessment Questionnaires (TRAQs) were completed in 21 (64%)
      of the 33 identified patients, with a mean TRAQ skill score of 66.62 out of 100.
      There was no correlation between better TRAQ scores and hemoglobin A1c level.
      Participants had lower baseline TRAQ scores for appointment keeping and tracking
      health issues. Participants were confident managing daily activities, talking
      with providers, and managing medications.

PMID- 27692974
TI  - Bundled Payment for Gastrointestinal Hemorrhage.

PMID- 27692973
TI  - Waking up is the hardest thing I do all day: Sleep inertia and sleep drunkenness.
AB  - The transition from sleep to wake is marked by sleep inertia, a distinct state
      that is measurably different from wakefulness and manifests as performance
      impairments and sleepiness. Although the precise substrate of sleep inertia is
      unknown, electroencephalographic, evoked potential, and neuroimaging studies
      suggest the persistence of some features of sleep beyond the point of awakening.
      Forced desynchrony studies have demonstrated that sleep inertia impacts cognition
      differently than do homeostatic and circadian drives and that sleep inertia is
      most intense during awakenings from the biological night. Recovery sleep after
      sleep deprivation also amplifies sleep inertia, although the effects of deep
      sleep vary based on task and timing. In patients with hypersomnolence disorders,
      especially but not exclusively idiopathic hypersomnia, a more pronounced period
      of confusion and sleepiness upon awakening, known as "sleep drunkenness", is
      common and problematic. Optimal treatment of sleep drunkenness is unknown,
      although several medications have been used with benefit in small case series.
      Difficulty with awakening is also commonly endorsed by individuals with mood
      disorders, disproportionately to the general population. This may represent an
      important treatment target, but evidence-based treatment guidance is not yet
      available.

PMID- 27692975
TI  - Exposure of juvenile turbot (Scophthalmus maximus) to silver nanoparticles and
      17alpha-ethinylestradiol mixtures: Implications for contaminant uptake and plasma
      steroid hormone levels.
AB  - Combined exposure to engineered nanoparticles (ENPs) and anthropogenic
      contaminants can lead to changes in bioavailability, uptake and thus effects of
      both groups of contaminants. In this study we investigated effects of single and
      combined exposures of silver (Ag) nanoparticles (AgNPs) and the synthetic hormone
      17alpha-ethinylestradiol (EE2) on tissue uptake of both contaminants in juvenile
      turbot (Scophthalmus maximus). Silver uptake and tissue distribution (gills,
      liver, kidney, stomach, muscle and bile) were analyzed following a 14-day, 2-h
      daily pulsed exposure to AgNPs (2 MUg L-1 and 200 MUg L-1), Ag+ (50 MUg L-1), EE2
      (50 ng L-1) and AgNP + EE2 (2 or 200 MUg L-1+50 ng L-1). Effects of the exposures
      on plasma vitellogenin (Vtg) levels, EE2 and steroid hormone concentrations were
      investigated. The AgNP and AgNP + EE2 exposures resulted in similar Ag
      concentrations in the tissues, indicating that combined exposure did not
      influence Ag uptake in tissues. The highest Ag concentrations were found in
      gills. For the Ag+ exposed fish, the highest Ag concentrations were measured in
      the liver. Our results show dissolution processes of AgNPs in seawater,
      indicating that the tissue concentrations of Ag may partly originate from ionic
      release. Plasma EE2 concentrations and Vtg induction were similar in fish exposed
      to the single contaminants and the mixed contaminants, indicating that the
      presence of AgNPs did not significantly alter EE2 uptake. Similarly,
      concentrations of most steroid hormones were not significantly altered due to
      exposures to the combined contaminants versus the single compound exposures.
      However, high concentrations of AgNPs in combination with EE2 caused a drop of
      estrone (E1) (female fish) and androstenedione (AN) (male and female fish) levels
      in plasma below quantification limits. Our results indicate that the interactive
      effects between AgNPs and EE2 are limited, with only high concentrations of AgNPs
      triggering synergistic effects on plasma steroid hormone concentrations in
      juvenile turbots.

PMID- 27692976
TI  - Pharmacodynamic Effects of Single and Multiple Doses of Empagliflozin in Patients
      With Type 2 Diabetes.
AB  - PURPOSE: Our aim was to investigate the effects of the sodium glucose
      cotransporter 2 inhibitor empagliflozin on urinary and serum glucose and
      electrolytes, urinary volume, osmolality, and the renin-angiotensin system in
      patients with type 2 diabetes. METHODS: In an open-label study, 22 patients
      receiving metformin (median age 56 years; range 40-65 years) received
      empagliflozin 25 mg once daily for 5 days. Food, fluid, and sodium intake were
      standardized for 3 days before and during treatment. FINDINGS: Twenty patients
      completed treatment. After single and multiple doses of empagliflozin, mean (SE)
      changes from baseline in 24-hour urinary glucose excretion were 463.3 (57.3)
      mmol/d and 599.5 (60.0) mmol/d, respectively (83.5 [10.3] g/d and 108.0 [10.8]
      g/d, respectively) (both P < 0.001), and in fasting serum glucose concentration
      were -1.8 (0.4) mmol/L and -1.1 (0.3) mmol/L, respectively (both P < 0.001).
      After a single dose, mean (SE) change from baseline in urine sodium excretion was
      45.3 (9.6) mmol/d (P < 0.001), and in urine volume was 341.0 (140.5) g/d (P =
      0.025), but there were no changes compared with baseline in either parameter
      after multiple doses. There were no changes in plasma renin or serum aldosterone
      with single or multiple doses of empagliflozin. There was a nonsignificant
      reduction in weight after a single dose of empagliflozin and a mean (SE) change
      of -1.4 (0.5) kg after multiple doses (P = 0.020). IMPLICATIONS: Empagliflozin 25
      mg increased urinary glucose excretion and decreased serum glucose and weight
      with transient natriuresis and increases in urine volume, without significant
      changes in the renin-angiotensin system. Clinicaltrials.gov Identifier:
      NCT01276288.

PMID- 27692977
TI  - Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas
      aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature
      Review and Network Meta-analysis.
AB  - PURPOSE: In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium,
      aztreonam, and levofloxacin) are currently approved for the treatment of chronic
      Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF).
      Levofloxacin inhalation solution (LIS) is the most recently approved inhaled
      antibiotic for adult patients with CF. A systematic literature review and
      Bayesian network meta-analysis (NMA) was conducted to compare the relative short
      term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics
      versus LIS. METHODS: A systematic literature search was conducted on February 16,
      2016, using EMBASE and Medline via OvidSP. All randomized controlled trials
      comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of
      follow-up were evaluated. NMA was performed for the following outcomes: relative
      and absolute percent changes from baseline in forced expiratory volume in 1
      second (FEV1%) predicted, change in P aeruginosa sputum density, respiratory
      symptoms score from the CF questionnaire-revised, hospitalization, additional
      antibiotics use, and study withdrawal rates. RESULTS: Of the 685 articles
      identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique
      studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in
      the greatest numerically increase in FEV1% predicted at 4 weeks, whereas LIS were
      predicted to be numerically greater than colistimethate sodium, tobramycin
      inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the
      95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks,
      none of the treatments was significantly more effective than LIS. The estimates
      for the mean change from baseline to 24 weeks in relative FEV1% versus LIS was 
      0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for
      aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to
      -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24
      weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP,
      and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P
      aeruginosa sputum density scores, additional use of antipseudomonal antibiotics,
      and study withdrawal rates were comparable among all inhaled antibiotics at all
      times. IMPLICATIONS: Based on this NMA, the analyses for many of the outcomes did
      not provide significant evidence to indicate that the other approved inhaled
      antibiotics were more effective than LIS for the treatment of chronic P
      aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to
      be comparable among these inhaled antibiotics.

PMID- 27692979
TI  - Fatal Kounis syndrome with stent thrombosis secondary to amoxicillin/clavulanic
      acid use: A case report and literature review.
AB  - Anaphylactic reactions are often induced by drugs, and the most frequent ones are
      penicillin derivates. The concurrence of acute coronary syndrome with
      hypersensitivity and anaphylactic or anaphylactoid reactions constitutes the
      Kounis syndrome. We report a case of a coronary stent thrombosis with a fatal
      outcome complicating an anaphylactic shock induced by amoxicillin-clavulanic acid
      association. A 58-year-old woman with a history of triple coronary stenting was
      treated by amoxicillin/clavulanic acid association for pharyngitis. One hour
      after the first drug intake, she developed an anaphylactic shock with acute
      constricting chest pain. She received intravenous hydrocortisone and was
      transferred to emergency department. The patient received epinephrine
      intravenously with fluid perfusion and oxygen. Electrocardiogram showed Pardee
      waves in the anterior precordial leads. Cardiac enzyme levels (troponin I) were
      disturbed. The patient was transferred to the coronary care unit with a diagnosis
      of acute myocardial infarction. The coronary angiography revealed anterior
      interventricular stent thrombosis. The patient experienced a cardiogenic shock
      with an important hemodynamic repercussion, and she died few hours later despite
      emergency care. The responsibility of amoxicillin-clavulanic acid association was
      retained in the genesis of this anaphylactic shock in front of a suggestive
      delay, a compatible evolution and a high semiotic score. Amoxicillin/clavulanic
      acid use may cause Kounis syndrome. The use of epinephrine is a challenging
      decision. We suggest that Kounis syndrome should be considered in the
      differential diagnosis of acute coronary syndrome.

PMID- 27692978
TI  - Intolerance to non-steroidal anti-inflammatory drugs.

PMID- 27692980
TI  - [Automated grouping of terms associated to cardiac valve fibrosis in MedDRA].
AB  - AIM: To propose an alternative approach for building custom groupings of terms
      that complements the usual approach based on both hierarchical method (selection
      of reference groupings in medical dictionary for regulatory activities [MedDRA])
      and/or textual method (string search), for case reports extraction from a
      pharmacovigilance database in response to a safety problem. Here we take cardiac
      valve fibrosis as an example. METHODS: The list of terms obtained by an automated
      approach, based on querying ontology of adverse drug reactions (OntoADR), a
      knowledge base defining MedDRA terms through relationships with systematized
      nomenclature of medicine-clinical terms (SNOMED CT) concepts, was compared with
      the reference list consisting of 53 preferred terms obtained by hierarchical and
      textual method. Two queries were performed on OntoADR by using a dedicated
      software: OntoADR query tools. Both queries excluded congenital diseases, and
      included a procedure or an auscultation method performed on cardiac valve
      structures. Query 1 also considered MedDRA terms related to fibrosis, narrowing
      or calcification of heart valves, and query 2 MedDRA terms described according to
      one of these four SNOMED CT terms: "Insufficiency", "Valvular sclerosis", "Heart
      valve calcification" or "Heart valve stenosis". RESULTS: The reference grouping
      consisted of 53 MedDRA preferred terms. Our automated method achieved recall of
      79% and precision of 100% for query 1 privileging morphological abnormalities,
      and recall of 100% and precision of 96% for query 2 privileging functional
      abnormalities. CONCLUSION: An alternative approach to MedDRA reference groupings
      for building custom groupings is feasible for cardiac valve fibrosis. OntoADR is
      still in development. Its application to other adverse reactions would require
      significant work for a knowledge engineer to define every MedDRA term, but such
      definitions could then be queried as many times as necessary by pharmacovigilance
      professionals.

PMID- 27692981
TI  - The pertussis hypothesis: Bordetella pertussis colonization in the pathogenesis
      of Alzheimer's disease.
AB  - While a number of endogenous risk factors including age and genetics are
      established for Alzheimer's disease (AD), identification of acquired, potentially
      preventable or treatable causes, remains limited. In this paper, we review three
      epidemiologic case studies and present extensive biologic, immunologic and
      anatomic evidence to support a novel hypothesis that Bordetella pertussis (BP),
      the bacterium better known to cause whooping cough, is an important potential
      cause of AD. Cross-cultural documentation of nasopharyngeal subclinical BP
      colonization reflecting BP-specific mucosal immunodeficiency, proximate anatomy
      of intranasal mucosal surfaces to central nervous system (CNS) olfactory
      pathways, and mechanisms by which BP and BP toxin account for all hallmark
      pathology of AD are reviewed, substantiating biologic plausibility. Notably,
      respiratory BP infection and BP toxin secreted from subclinical BP colonization
      can account for the initiation and accumulation of amyloid beta plaques and tau
      tangles. Additional mechanisms consistent with the immunobiologic effects of
      subclinical BP colonization include microglial activation and inflammation,
      atrophy and neurodegeneration, excitotoxicity, distinctive anatomic distribution
      and sequential spread of disease, impaired glucose utilization, and other
      characteristic CNS pathology of AD. We conclude by assessing the evidence for
      causation against the Bradford Hill criteria, and advocate for further
      investigation into the potential role of BP in the etiology of AD.

PMID- 27692982
TI  - mTORC1 inhibition with rapamycin exacerbates adipose tissue inflammation in obese
      mice and dissociates macrophage phenotype from function.
AB  - Genetic- and diet-induced obesity and insulin resistance are associated with an
      increase in mechanistic target of rapamycin complex (mTORC) 1 activity in adipose
      tissue. We investigated herein the effects of pharmacological mTORC1 inhibition
      in the development of adipose tissue inflammation induced by high-fat diet (HFD)
      feeding, as well as in the polarization, metabolism and function of bone marrow
      derived macrophages (BMDM). For this, C57BL/6J mice fed with a standard chow diet
      or a HFD (60% of calories from fat) and treated with either vehicle (0.1% Me2SO,
      0.2% methylcellulose) or rapamycin (2mg/kg/ day, gavage) during 30days were
      evaluated for body weight, adiposity, glucose tolerance and adipose tissue
      inflammation. Although rapamycin did not affect the increase in body weight and
      adiposity, it exacerbated the glucose intolerance and adipose tissue inflammation
      induced by HFD feeding, as evidenced by the increased adipose tissue percentage
      of M1 macrophages, naive and activated cytotoxic T lymphocytes, and mRNA levels
      of proinflammatory molecules, such as TNF-alpha, IL-6 and MCP-1. In BMDM in
      vitro, pharmacological mTORC1 inhibition induced phosphorylation of NFkappaB p65
      and spontaneous polarization of macrophages to a proinflammatory M1 profile,
      while it impaired M2 polarization induced by IL-4+IL-13, glycolysis and
      phagocytosis. Altogether, these findings indicate that mTORC1 activity is an
      important determinant of adipose tissue inflammatory profile and macrophage
      plasticity, metabolism and function.

PMID- 27692983
TI  - Medium-chain Fatty Acids as Biomarkers of Mitochondrial Dysfunction in Traumatic
      Brain Injury.

PMID- 27692984
TI  - Wnt Signalosome Assembly by DEP Domain Swapping of Dishevelled.
AB  - Extracellular signals are often transduced by dynamic signaling complexes
      ("signalosomes") assembled by oligomerizing hub proteins following their
      recruitment to signal-activated transmembrane receptors. A paradigm is the Wnt
      signalosome, which is assembled by Dishevelled via reversible head-to-tail
      polymerization by its DIX domain. Its activity causes stabilization of beta
      catenin, a Wnt effector with pivotal roles in animal development and cancer. How
      Wnt triggers signalosome assembly is unknown. Here, we use structural analysis,
      as well as biophysical and cell-based assays, to show that the DEP domain of
      Dishevelled undergoes a conformational switch, from monomeric to swapped dimer,
      to trigger DIX-dependent polymerization and signaling to beta-catenin. This
      occurs in two steps: binding of monomeric DEP to Frizzled followed by DEP domain
      swapping triggered by its high local concentration upon Wnt-induced recruitment
      into clathrin-coated pits. DEP domain swapping confers directional bias on
      signaling, and the dimerization provides cross-linking between Dishevelled
      polymers, illustrating a key principle underlying signalosome formation.

PMID- 27692985
TI  - Monoubiquitination of Histone H2B Blocks Eviction of Histone Variant H2A.Z from
      Inducible Enhancers.
AB  - Covalent modifications of histones play a crucial role in the regulation of gene
      expression. Histone H2B monoubiquitination has mainly been described as a
      regulator of transcription elongation, but its role in transcription initiation
      is poorly documented. We investigated the role of this histone mark (H2Bub1) on
      different inducible enhancers, in particular those regulated by estrogen receptor
      alpha, by loss- and gain-of-function experiments with the specific E3-ubiquitin
      ligase complex of H2B: RNF20/RNF40. RNF20/RNF40 overexpression causes repression
      of the induced activity of these enhancers. Genome-wide profiles show that H2Bub1
      levels are negatively correlated with the accessibility of enhancers to
      transcriptional activators. We found that the chromatin association of histone
      variant H2A.Z, which is evicted from enhancers for transcriptional activation, is
      stabilized by H2Bub1 by impairing access of the chromatin remodeler INO80. We
      propose that H2Bub1 acts as a gatekeeper of H2A.Z eviction and activation of
      inducible enhancers.

PMID- 27692986
TI  - USP38 Inhibits Type I Interferon Signaling by Editing TBK1 Ubiquitination through
      NLRP4 Signalosome.
AB  - TBK1 is a component of the type I interferon (IFN) signaling pathway, yet the
      mechanisms controlling its activity and degradation remain poorly understood.
      Here we report that USP38 negatively regulates type I IFN signaling by targeting
      the active form of TBK1 for degradation in vitro and in vivo. USP38 specifically
      cleaves K33-linked poly-ubiquitin chains from TBK1 at Lys670, and it allows for
      subsequent K48-linked ubiquitination at the same position mediated by DTX4 and
      TRIP. Knockdown or knockout of USP38 increases K33-linked ubiquitination, but it
      abrogates K48-linked ubiquitination and degradation of TBK1, thus enhancing type
      I IFN signaling. Our findings identify an essential role for USP38 in negatively
      regulating type I IFN signaling, and they provide insights into the mechanisms by
      which USP38 regulates TBK1 ubiquitination through the NLRP4 signalosome.

PMID- 27692987
TI  - Neurocognitive Function in Children with Primary Hypertension.
AB  - OBJECTIVE: To compare neurocognitive test performance of children with primary
      hypertension with that of normotensive controls. STUDY DESIGN: Seventy-five
      children (10-18 years of age) with newly diagnosed, untreated hypertension and 75
      frequency-matched normotensive controls had baseline neurocognitive testing as
      part of a prospective multicenter study of cognition in primary hypertension.
      Subjects completed tests of general intelligence, attention, memory, executive
      function, and processing speed. Parents completed rating scales of executive
      function and the Sleep-Related Breathing Disorder scale of the Pediatric Sleep
      Questionnaire (PSQ-SRBD). RESULTS: Hypertension and control groups did not differ
      significantly in age, sex, maternal education, income, race, ethnicity, obesity,
      anxiety, depression, cholesterol, glucose, insulin, and C-reactive protein.
      Subjects with hypertension had greater PSQ-SRBD scores (P = .04) and
      triglycerides (P = .037). Multivariate analyses showed that hypertension was
      independently associated with worse performance on the Rey Auditory Verbal
      Learning Test (List A Trial 1, P = .034; List A Total, P = .009; Short delay
      recall, P = .013), CogState Groton Maze Learning Test delayed recall (P = .002),
      Grooved Pegboard dominant hand (P = .045), and Wechsler Abbreviated Scales of
      Intelligence Vocabulary (P = .016). Results indicated a significant interaction
      between disordered sleep (PSQ-SRBD score) and hypertension on ratings of
      executive function (P = .04), such that hypertension heightened the association
      between increased disordered sleep and worse executive function. CONCLUSIONS:
      Youth with primary hypertension demonstrated significantly lower performance on
      neurocognitive testing compared with normotensive controls, in particular, on
      measures of memory, attention, and executive functions.

PMID- 27692988
TI  - An outbreak of Kyasanur forest disease in the Wayanad and Malappuram districts of
      Kerala, India.
AB  - Kyasanur forest disease (KFD) is a zoonotic viral haemorrhagic fever and has been
      endemic to Karnataka State, India. Outbreaks of KFD were reported in new areas of
      Wayanad and Malappuram districts of Kerala, India during 2014-2015. Investigation
      of the outbreaks was carried out in these districts during May 2015. The line
      list data of KFD cases available with District Medical Office, Wayanad were
      analysed. Case investigation was carried out to determine the risk factors
      associated with the outbreak and possible site of contraction infections. Ticks
      from the forest floor were collected in areas associated with monkey deaths by
      flagging method to estimate species abundance. Of 102 confirmed cases of KFD
      reported in Wayanad, 91% were adults aged >15years. About 43% of the cases were
      from the areas of Poothady Primary Health Centre (PHC) followed by Chethalayam
      PHC (22%). Most of the affected individuals belong to Kattunayakan tribe,
      dependent on forest for their livelihood. Those tribes are engaged in trench
      digging and fire line works in summer months and hence are at a higher risk. In
      Malappuram, the Cholanaickan tribe, are under high risk of exposure to infected
      ticks as they live deep in the forest and trap monkeys for game meat. High
      abundance of Haemaphysalis spinigera and H. turturis, the established vectors of
      KFD virus was recorded in all affected areas. Incidence of KFD cases/monkey
      deaths and high abundance of Haemaphysalis vectors in the forest ranges of
      Wayanad and Malappuram districts indicate that the area has become receptive for
      KFD outbreaks. Preventive measures (vaccination of high risk groups) coupled with
      intensive health education should be carried out prior to transmission season.

PMID- 27692990
TI  - Body adiposity predictors of vitamin D status in nondialyzed patients with
      chronic kidney disease: A cross-sectional analysis in a tropical climate city.
AB  - OBJECTIVES: The association of vitamin D status with high body adiposity is
      poorly investigated in the chronic kidney disease (CKD) population. The aim of
      the present study was to describe vitamin D status and to identify body adiposity
      predictors of vitamin D deficiency, in a nondialyzed CKD population inhabiting a
      tropical city. METHODS: This cross-sectional study included patients with CKD,
      defined as estimated glomerular filtration rate (eGFR) <60 mL/min, regularly
      treated by an interdisciplinary team in an outpatient university clinic, set in a
      Brazilian city (latitude: 22 degrees 54'S; 43 degrees 12'W). Adiposity parameters
      analyzed were body mass index (BMI), total body adiposity (dual-energy x-ray
      absorptiometry [DXA] and body adiposity index [BAI]), and central body adiposity
      (DXA-trunk fat and waist-to-height ratio [WHtR]). Laboratory parameters included
      serum concentrations of 25-hydroxyvitamin D, phosphate, parathyroid hormone, and
      insulin (insulin resistance [IR evaluation: homeostasis model assessment; HOMA]).
      RESULTS: We studied 244 patients (54.9% men; n = 134) with median eGFR = 29.1
      mL/min and BMI 26.1 kg/m2, comprising 58.2% (n = 142) with overweight/obesity.
      The vitamin D status was sufficient (>=30 ng/dL) in 43%, insufficient (20-30
      ng/dL) in 37%, and deficient (<20 ng/dL) in 20%. Total body adiposity was the
      independent predictor of vitamin D deficiency (DXA: odds ratio [OR], 2.3; 95%
      confidence interval [CI], 1.1-5; P = 0.03; BAI: OR, 1.9; 95% CI, 1-3.8; P =
      0.02), whereas BMI, DXA-trunk fat, and WHtR showed no correlation. Higher serum
      phosphorus and hyperparathyroidism were related (P < 0.05) to vitamin D
      deficiency. IR was not independently associated with 25-hydroxyvitamin D
      concentration. CONCLUSIONS: Just under half of the CKD population presented
      sufficient concentration of 25-hydroxyvitamin D. Total body adiposity,
      independent of age and eGFR, regardless if evaluated by DXA or BAI, was the
      predictor of vitamin D deficiency, which in turn was associated with higher serum
      phosphorus and hyperparathyroidism, but not with IR.

PMID- 27692989
TI  - Serum adiponectin and protein-energy wasting in predialysis chronic kidney
      disease.
AB  - OBJECTIVE: Adiponectin (ADPN) has antiatherogenic, anti-inflammatory, and insulin
      sensitizing effects. Serum ADPN levels are increased in patients with chronic
      kidney diseases (CKD), and higher ADPN is paradoxically a predictor of mortality
      in these patients. The aim of this study was to determine the association between
      serum ADPN levels and protein-energy wasting (PEW) in predialysis CKD. METHOD: We
      examined serum ADPN concentrations and PEW in 1303 patients from the KNOW-CKD
      (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease) study.
      PEW was defined as the presence of three or more of the following four
      indicators: serum albumin <3.8 g/dL, body mass index <23 kg/m2, urine creatinine
      excretion (UCE) below the lower quartile, and daily dietary protein intake <0.6
      g/kg. We analyzed the association between PEW and ADPN using a multivariate
      regression model after adjustment for socioeconomic factors, comorbidities, and
      laboratory findings. RESULTS: Among 1303 predialysis CKD patients, 72 (5.5%) had
      PEW. In multivariate logistic regression analysis, higher ADPN level was
      associated with PEW (odds ratio, 1.04; 95% confidence interval [CI], 1.01-1.08 by
      1 MUg/mL ADPN). The highest ADPN quartile was associated with PEW in comparison
      with the lowest quartile (odds ratio, 10.54; 95% CI, 1.28-86.74). In multiple
      linear regression with PEW indicators, ADPN was more strongly associated with UCE
      (beta = -2.21; 95% CI, -4.13 to -0.28; R2 = 0.67). CONCLUSION: High ADPN is
      independently associated with PEW. Among PEW indicators, serum ADPN is closely
      associated with UCE as an indirect measure of muscle mass.

PMID- 27692991
TI  - Chronic brain damage in sickle cell disease and its relation with quality of
      life.
AB  - BACKGROUND AND OBJECTIVE: Sickle cell anaemia causes progressive organ damage.
      The objective is to describe school performance of patients with sickle cell
      anaemia and their clinical parameters and quality of life that may have an
      influence. The hypothesis is that if school alterations occur without other
      objective data, additional factors must be present besides the disease itself.
      PATIENTS AND METHODS: Transversal study performed in November 2015 considering
      analytical variables, complications and neuroradiological images of children with
      sickle cell anaemia, and family survey on school performance and quality of life.
      RESULTS: Median age was 6.8 years and 78% were diagnosed at birth. Sixty patients
      were included. School performance was altered in 51% of cases and was related to
      nocturnal hypoxemia. Acute stroke incidence was 6.7%. Transcranial ultrasound was
      abnormal in 4% of cases and magnetic resonance imaging in 16% of cases. Quality
      of life showed pathological findings in all areas and the low values increased
      proportionally in older ages. The stroke affected the physical and social sphere,
      and lung disease affected the physical and emotional spheres. CONCLUSIONS: Poor
      school performance affects half of the patients and it is related to nocturnal
      hypoxemia, although other socio-cultural factors may have an influence. Quality
      of life is affected in most of these cases independently of academic results. The
      absence of alterations in neuroimaging or the apparent lack of severe clinical
      parameters do not mean that quality of life and schooling are normal.

PMID- 27692992
TI  - Neurobiology of Congenital Amusia.
AB  - The past decade of research has provided compelling evidence that musical
      engagement is a fundamental human trait, and its biological basis is increasingly
      scrutinized. In this endeavor, the detailed study of individuals who have musical
      deficiencies is instructive because of likely neurogenetic underpinnings. Such
      individuals have 'congenital amusia', an umbrella term for lifelong musical
      disabilities that cannot be attributed to intellectual disability, lack of
      exposure, or brain damage after birth. Key points are reviewed here that have
      emerged during recent years regarding the neurobiology of the disorder, focusing
      on the importance of recurrent processing between the right inferior frontal
      cortex and the auditory cortex for conscious monitoring of musical pitch, and how
      this relates to developmental cognitive disorders in general.

PMID- 27692993
TI  - [Craniofacial strategy for syndromic craniosynostosis].
AB  - The complexity of treatment of faciocraniosynostosis justifies the treatment in a
      reference center for rare diseases. The growth disturbances in the skull and face
      being variable according to the type of mutation in the FGFr (Crouzon, Pfeiffer,
      Apert), the strategy is adapted to the phenotype according to the following
      principles: posterior expansion with or without distraction around 6 months to
      limit the descent of the cerebellum tonsils and to prevent the turricephalic
      development; fronto-facial monobloc advancement with internal distraction around
      the age of 18 months in case of severe exorbitism or breathing impairment. The
      dissociated strategy (fronto-orbital advancement first, followed by facial
      osteotomy of Le Fort 3 type). The growing evolution dictates the sequence of
      subsequent surgeries according to the monitoring of intracranial pressure by
      fundus examination and of the respiration by polysomnography. Le Fort 3 and
      transversal maxillary distraction may be repeated if necessary. Orthognathic
      surgery is almost always compulsory after the age of 14, before the aesthetic
      refinements which can be undertaken ultimately (rhinoplasty, genioplasty,
      canthopexies, fat grafting...).

PMID- 27692994
TI  - Synthesis of monomeric and dimeric steroids containing [1,2,4]triazolo[1,5
      a]pyrimidines.
AB  - The synthesis of several monomeric and dimeric steroidal [1,2,4]triazolo[1,5
      a]pyrimidines (TPs) derived from steroids are described. These derivatives were
      prepared from alpha,beta-unsaturated carbonyl compounds through a Claisen Schmidt
      condensation and rearrangement of the spiro moiety followed by a cycloaddition
      with 3-amino-1,2,4-triazole. The antiproliferative activity of compounds 7, 13-15
      was tested against human cancer cells; several IG50 values were below 10MUM.

PMID- 27692995
TI  - Synthesis and structure-activity relationships of 1-benzylindane derivatives as
      selective agonists for estrogen receptor beta.
AB  - The estrogen receptor beta (ERbeta) selective agonist is considered a promising
      candidate for the treatment of estrogen deficiency symptoms in ERbeta-expressing
      tissues, without the risk of breast cancer, and multiple classes of compounds
      have been reported as ERbeta selective agonists. Among them, 6-6 bicyclic ring
      containing structures (e.g., isoflavone phytoestrogens) are regarded as one of
      the cyclized analogues of isobutestrol 5b, and suggest that other cyclized
      scaffolds comprising 5-6 bicyclic rings could also act as selective ERbeta
      ligands. In this study, we evaluated the selective ERbeta agonistic activity of 1
      (4-hydroxybenzyl)indan-5-ol 7a and studied structure-activity relationship (SAR)
      of its derivatives. Some functional groups improved the properties of 7a;
      introduction of a nitrile group on the indane-1-position resulted in higher
      selectivity for ERbeta (12a), and further substitution with a fluoro or a methyl
      group to the pendant phenyl ring was also preferable (12b, d, and e). Subsequent
      chiral resolution of 12a identified that R-12a has a superior profile over S-12a.
      This is comparable to diarylpropionitrile (DPN) 5c, one of the promising
      selective ERbeta agonists and indicates that this indane-based scaffold has the
      potential to provide better ERbeta agonistic probes.

PMID- 27692997
TI  - Response to the Letter to the Editor by Shinji Matsunaga "Combination Therapy
      Showed Limited Superiority Over Monotherapy for Alzheimer Disease: A Meta
      analysis of 14 Randomized Trials".

PMID- 27692998
TI  - Alternative Names to SNFist.

PMID- 27692996
TI  - Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase
      B inhibitors in Parkinson's disease.
AB  - The benzyloxy substituted small molecules are well-known highly potent monoamine
      oxidase B inhibitors, but their therapeutic potential against Parkinson's disease
      have not been investigated in detail. In this paper, a series of representative
      benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B
      inhibition. In addition, their neuroprotective effects were investigated in 6
      OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds
      exhibited a marked increase in survival of PC12 cells which treated with the
      neurotoxins. Among them, 13 exhibited remarkable and balanced neuroprotective
      potency. The protective effects of 13 against neurotoxins-induced apoptosis were
      confirmed with flow cytometry and staining methods. Furthermore, 13 also showed
      good BBB permeability and low toxicity according to in vitro BBB prediction and
      in vivo acute toxicity test. The results indicated that 13 is an effective and
      promising candidate to be further developed as disease-modifying drug for
      Parkinson's disease therapy.

PMID- 27692999
TI  - [Functional treatment of children subcondylar fractures: An axiographic
      assessment].
AB  - INTRODUCTION: Subcondylar fractures are common in children. Occlusion disorders
      resulting from these fractures in deciduous or mixed dentition do not have as
      much impact as in adults due to alveolar adaption possibilities. Functional
      treatment allows for good functional results, but does not treat the dynamic
      shortening of the ramus. The objective of this study was to evaluate the
      axiographic condylar slope changes after subcondylar fracture in children.
      MATERIALS AND METHODS: A prospective study was conducted from 2010 to 2015,
      including all the under-18 patients presenting with a subcondylar fracture.
      Examination by mean of a Quick Axis axiograph measured the length of propulsion
      and the condylar inclination on both sides. The main evaluation criterion was the
      amount of condylar inclination decrease on the fractured side. RESULTS: Twelve
      patients (mean age: 10.42; 5-16) were included. Eleven children had a loss of
      condylar inclination on the fractured side without occlusion disorders at 33.2
      months on average (3-144 months) after the initial trauma. Only one patient had
      symmetric axiographies without loss of condylar inclination on the fractured
      side. DISCUSSION: Dynamic shortening of the ramus on the side of the subcondylar
      fracture is consistent at short and medium terms in children. Surgical treatment
      may be the solution for avoiding this dynamic disorder of the mandible and should
      be evaluated.

PMID- 27693000
TI  - High prevalence of nontoxigenic Clostridium difficile isolated from hospitalized
      and non-hospitalized individuals in rural Ghana.
AB  - Since data about Clostridium difficile infection in sub-Saharan Africa are
      scarce, we determined its epidemiology and risk factors in a cross-sectional
      study in Eikwe, a rural community in Ghana. We tested stool samples from 176
      hospitalized patients with diarrhoea and from 131 asymptomatic non-hospitalized
      individuals for C. difficile and some other enteric pathogens. The overall
      prevalence rate of C. difficile was 4.9% with ribotype 084 being predominant.
      With 75% of the isolates, a high rate of nontoxigenic strains was present in
      symptomatic patients, most of whom had no other identified enteric pathogens. All
      strains were susceptible against metronidazole and vancomycin, respectively. Data
      on lifestyle and medical history showed that age <5years (p=0.004), and use of
      ceftriaxone (p=0.023) were the most important risk factors for C. difficile
      carriage status. Although our data suggest that C. difficile is currently not a
      major cause of diarrhoea in this setting, the epidemiology of C. difficile in sub
      Saharan Africa awaits further investigation.

PMID- 27693001
TI  - Accelerated Accumulation of Multimorbidity After Bilateral Oophorectomy: A
      Population-Based Cohort Study.
AB  - OBJECTIVE: To study the association between bilateral oophorectomy and the rate
      of accumulation of multimorbidity. PATIENTS AND METHODS: In this historical
      cohort study, the Rochester Epidemiology Project records-linkage system was used
      to identify all premenopausal women who underwent bilateral oophorectomy before
      age 50 years between January 1, 1988, and December 31, 2007, in Olmsted County,
      Minnesota. Each woman was randomly matched to a referent woman born in the same
      year (+/-1 year) who had not undergone bilateral oophorectomy. We studied the
      rate of accumulation of 18 common chronic conditions over a median of
      approximately 14 years of follow-up. RESULTS: Although women who underwent
      bilateral oophorectomy already had a higher multimorbidity burden at the time of
      oophorectomy, they also experienced an increased risk of subsequent
      multimorbidity. After adjustments for 18 chronic conditions present at baseline,
      race/ethnicity, education, body mass index, smoking, age at baseline, and
      calendar year at baseline, women who underwent oophorectomy before age 46 years
      experienced an increased risk of depression, hyperlipidemia, cardiac arrhythmias,
      coronary artery disease, arthritis, asthma, chronic obstructive pulmonary
      disease, and osteoporosis. In addition, they experienced an accelerated rate of
      accumulation of the 18 chronic conditions considered together (hazard ratio,
      1.22; 95% CI, 1.14-1.31; P<.001). Several of these associations were reduced in
      women who received estrogen therapy. CONCLUSION: Bilateral oophorectomy is
      associated with a higher risk of multimorbidity, even after adjustment for
      conditions present at baseline and for several possible confounders. However,
      several of these associations were reduced in women who received estrogen
      therapy.

PMID- 27693003
TI  - Electronic cigarettes increase endothelial progenitor cells in the blood of
      healthy volunteers.
AB  - BACKGROUND AND AIMS: The use of electronic cigarettes is increasing dramatically
      on a global scale and its effects on human health remain uncertain. In the
      present study, we measured endothelial progenitor cells (EPCs) and microvesicles
      (MVs) in healthy young volunteers following short-term exposure to inhalation of
      e-cigarette vapor (ECV) to determine vascular changes. METHODS: Sixteen healthy
      seldom smokers were randomized into two groups either exposed or not exposed to
      10 puffs of ECV for 10 min, in a crossover design. Blood samples were obtained at
      baseline and 1, 4 and 24 h following exposure. EPCs (CD34 + CD309) and MVs were
      analyzed by flow cytometry. MVs were phenotyped according to origin (platelet
      (CD41), endothelial (CD144), leukocytes (CD45), monocytes (CD14)) and nuclear
      content (SYTO 13 dye). In addition, expression of inflammation markers such P
      selectin (CD62P), E-selectin (CD62E), CD40-ligand (CD154) and HMGB1 was
      investigated. Fractional exhaled nitric oxide (FeNO) was also measured at
      baseline and after 24 h. RESULTS: EPC levels in blood were significantly
      increased 1 h following exposure to ECV and returned to baseline values after 24
      h. Only E-selectin positive MVs (endothelial origin) were slightly elevated (p <
      0.038). FeNO was unaffected by exposure to ECV. CONCLUSIONS: In healthy
      volunteers, ten puffs of e-cigarette vapor inhalation caused an increase in EPCs.
      This increase was of the same magnitude as following smoking of one traditional
      cigarette, as we previously demonstrated. Taken together, these results may
      represent signs of possible vascular changes after short e-cigarette inhalation.
      Further studies analyzing potential cardiovascular health effects are critical as
      the e-cigarette market continues to burgeon.

PMID- 27693004
TI  - Collective impact of conventional cardiovascular risk factors and coronary
      calcium score on clinical outcomes with or without statin therapy: The St Francis
      Heart Study.
AB  - BACKGROUND AND AIMS: The efficacy of statin therapy remains unknown in patients
      eligible for statin therapy with and without elevated coronary calcium score
      (CAC). The study sought to evaluate how cardiovascular risk factors, expressed in
      terms of statin eligibility for primary prevention, and CAC modify clinical
      outcomes with and without statin therapy. METHODS: We conducted a post-hoc
      analysis of the St. Francis Heart Study treatment trial, a double-blind, placebo
      controlled randomized controlled trial of atorvastatin (20 mg), vitamin C (1 g),
      and vitamin E (1000 U) daily, versus placebos in 990 asymptomatic individuals
      with CAC >= 80th percentile for age and gender. Primary cardiovascular outcomes
      included non-fatal myocardial infarction or coronary death, coronary
      revascularization, stroke, and peripheral arterial revascularization. We further
      stratified the treatment and placebo groups by eligibility (eligible when statin
      indicated) for statin therapy based on 2013 ACC/AHA guidelines and based on CAC
      categories. RESULTS: After a median follow-up of 4.8 years, cardiovascular events
      had occurred in 3.9% of the statin treated but not eligible, 4.6% of the
      untreated and not eligible, 8.9% of the treated and eligible and 13.4% of the
      untreated and eligible groups, respectively (p<0.001). Low CAC (<100) occurred
      infrequently in statin eligible subjects (<=4%) and was associated with low 10
      year event rate (<1 per 100 person-years). In contrast, high CAC (>300) occurred
      frequently in more than 35% of the statin not eligible subjects and was
      associated with a high 10-year event rate (>=17 per 100 person-years). Risk
      prediction improved significantly when both clinical risk profile and CAC score
      were combined (net reclassification index p = 0.002). CONCLUSIONS: Under the
      current statin treatment guidelines a small number of statin eligible subjects
      with low CAC might not benefit from statin therapy within 5 years. However, the
      statin not eligible subjects with high CAC have high event rate attributing to
      loss of opportunity for effective primary prevention.

PMID- 27693005
TI  - WITHDRAWN: Sentiment prediction by text mining medical documents using optimized
      swarm search-based feature selection.
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
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 27693002
TI  - The role of miRNAs in cardiovascular disease risk factors.
AB  - Coronary artery disease and atherosclerosis are complex pathologies that develop
      over time due to genetic and environmental factors. Differential expression of
      miRNAs has been identified in patients with coronary artery disease and
      atherosclerosis, however, their association with cardiovascular disease risk
      factors, including hyperlipidemia, hypertension, obesity, diabetes, lack of
      physical activity and smoking, remains unclear. This review examines the role of
      miRNAs as either biomarkers or potential contributors to the pathophysiology of
      these aforementioned risk factors. It is intended to provide an overview of the
      published literature which describes alterations in miRNA levels in both human
      and animal studies of cardiovascular risk factors and when known, the possible
      mechanism by which these miRNAs may exert either beneficial or deleterious
      effects. The intent of this review is engage clinical, translational, and basic
      scientists to design future collaborative studies to further elucidate the
      potential role of miRNAs in cardiovascular diseases.

PMID- 27693006
TI  - Progressive encephalopathy associated with nutritional deficiencies: Identifying
      patients at high risk for developing thiamine deficiency.

PMID- 27693007
TI  - Paired comparison of the sensitivity and specificity of multispectral digital
      skin lesion analysis and reflectance confocal microscopy in the detection of
      melanoma in vivo: A cross-sectional study.
AB  - BACKGROUND: Several technologies have been developed to aid dermatologists in the
      detection of melanoma in vivo including dermoscopy, multispectral digital skin
      lesion analysis (MDSLA), and reflectance confocal microscopy (RCM). To our
      knowledge, there have been no studies directly comparing MDSLA and RCM.
      OBJECTIVE: We conducted a repeated measures analysis comparing the sensitivity
      and specificity of MDSLA and RCM in the detection of melanoma (n = 55 lesions
      from 36 patients). METHODS: Study patients (n = 36) with atypical-appearing
      pigmented lesions (n = 55) underwent imaging by both RCM and MDSLA. Lesions were
      biopsied and analyzed by histopathology. RESULTS: RCM exhibited superior test
      metrics (P = .001, McNemar test) compared with MDSLA. Respectively, sensitivity
      measures were 85.7% and 71.4%, and specificity rates were 66.7% and 25.0%.
      LIMITATIONS: The sample size was relatively small and was collected from only one
      dermatologist's patient base; there was some degree of dermatopathologist
      interobserver variability; and only one confocalist performed the RCM image
      evaluations. CONCLUSION: RCM is a useful adjunct during clinical assessment of in
      vivo lesions suspicious for melanoma or those requiring re-excision because of
      high level of dysplasia or having features consistent with an atypical
      melanocytic nevus with severe cytologic atypia.

PMID- 27693008
TI  - Risk of serious infections, cutaneous bacterial infections, and granulomatous
      infections in patients with psoriasis treated with anti-tumor necrosis factor
      agents versus classic therapies: Prospective meta-analysis of Psonet registries.
AB  - BACKGROUND: Anti-tumor necrosis factor (TNF) therapy in psoriasis has been
      associated with an increased risk of serious infections compared with nonbiologic
      systemic therapies. OBJECTIVE: We sought to quantify the risk of: (1) serious
      infections (leading to hospitalization, sequelae, or death); and (2) "any
      infection," bacterial cutaneous infections, and granulomatous infections among
      patients receiving anti-TNF therapy compared with nonbiologics (acitretin,
      methotrexate, cyclosporine). METHODS: We used prospective meta-analysis to
      combine data from the Psocare registry (Italy), Biobadaderm registry (Spain), and
      Clalit Health Services database (Israel), including 17,739 patients and 23,357.5
      person-years of follow-up. RESULTS: For serious infections, age, gender, and
      Charlson morbidity index adjusted hazard ratio of exposure to anti-TNFs compared
      with nonbiologics was 0.98 (95% confidence interval 0.80-1.19), for bacterial
      cutaneous infections it was 1.00 (95% confidence interval 0.62-1.61), and for
      granulomatous infections it was 1.23 (95% confidence interval 0.82-1.84). Using
      methotrexate as comparator and comparing first year of exposure with later
      exposure did not modify the results. For any infectious episode, risks and
      relative risks were heterogeneous among registries, probably because of different
      definitions of outcome. LIMITATIONS: There was lack of power to describe risk of
      single drugs. CONCLUSION: In current clinical practice, treatment with anti-TNF
      drugs was not associated with a higher risk of serious infections than treatment
      with nonbiologic systemic therapy.

PMID- 27693009
TI  - Mugil curema as a PAH bioavailability monitor for Atlantic west sub-tropical
      estuaries.
AB  - This work aimed to evaluate the use of Mugil curema as a biomonitor for
      polycyclic aromatic hydrocarbon (PAH) bioavailability. Fish biliary metabolites
      from low-contaminated (Cananeia) and contaminated (Santos) Brazilian estuaries
      were analysed using a high-performance liquid chromatography apparatus coupled to
      fluorescence detectors connected in a series. In the Cananeia and Santos
      estuaries, total metabolite levels ranged from 0.85 to 34.4MUgg-1 of bile and
      from 4.06 to 528MUgg-1 of bile, respectively. Metabolite levels were not
      influenced by feeding status or sexual hormones (p<0.05), thus suggesting that M.
      curema is a good biomonitor for PAH bioavailability. In estuarine regions, it is
      possible to sample both the male and female genders of this species in any
      reproductive period.

PMID- 27693010
TI  - Effect of probiotics on respiratory, gastrointestinal and nutritional outcomes in
      patients with cystic fibrosis: A systematic review.
AB  - BACKGROUND: An increasing body of research investigating the use of probiotics to
      improve health outcomes in patients with cystic fibrosis (CF) prompted the need
      to systematically assess and summarise the relevant literature. METHODS: An
      electronic search of five databases and three trial databases was conducted.
      Studies describing the administration of probiotics to patients with CF older
      than 2years, with a comparator group on respiratory, gastrointestinal and
      nutritional outcomes were included. RESULTS: Three pre-post studies and six
      randomised controlled trials met the inclusion criteria. Overall studies showed a
      positive effect of probiotics on reducing the number of pulmonary exacerbations
      and decreasing gastrointestinal inflammation. There was limited effect of
      probiotics on other outcomes and inadequate evidence for the effects of specific
      probiotic species and strains. CONCLUSION: The findings suggest that probiotics
      may improve respiratory and gastrointestinal outcomes in a stable CF clinic
      population with no reported evidence of harm. There is inadequate evidence at
      this time to recommend a specific species, strain or dose of probiotic as likely
      to be of significant benefit.

PMID- 27693011
TI  - The nitric oxide serum level and combined utero-placental thickness in buffalo
      (Bubalus bubalis) affected by pregnancy pathology.
AB  - The present study aimed mainly to study the level of nitric oxide (NO) and
      combined thickness of the uterus and placenta (CTUP) in buffaloes affected by
      pregnancy pathology. Females (n = 104) were classified into three main groups:
      nonpregnant (n = 10), healthy pregnant (n = 54), and pathologically pregnant (n =
      40). The healthy pregnant animals were subgrouped according to the stage of
      pregnancy to early stage (n = 15), mid stage (n = 15), late stage (n = 19), and
      full term (n = 5). The animals in which pregnancy was associated with placental
      pathology were subgrouped to uterine torsion (n = 27), hydroallantois (n = 5),
      and abortion (n = 8). Blood samples were collected from all animals to estimate
      the NO level using Griess reaction test. Combined thickness of the uterus and
      placenta was measured at the most caudal part of the pregnant horn using a rectal
      ultrasound probe. Placental tissue samples were collected from all pregnant
      animals just after delivery or abortion for histopathologic section. The results
      revealed that the level of NO was higher (P <= 0.05) in pregnant than in
      nonpregnant animals (6.89 +/- 0.18 MUM). Additionally, NO level was decreased
      significantly at full term (18.26 +/- 0.27 MUM) when compared to the other stages
      of pregnancy. Moreover, there was a decrease (P <= 0.05) in the level of NO in
      cases of uterine torsion (22.22 +/- 0.46 MUM) and hydroallantois (24.20 +/- 0.07
      MUM) in comparison with the normal pregnant buffalo. The CTUP was significantly
      increased as pregnancy progressed. The CTUP in cases of uterine torsion (18.2 +/-
      3.3 mm) was higher (P < 0.05) than in healthy pregnant buffalo at the same stage
      of pregnancy. Additionally, CTUP significantly differed between different types
      of uterine torsion. There was no significant difference between CTUP in
      hydroallantois and abortion cases besides healthy pregnancy. Histopathologic
      examination revealed a great proliferation and hyperplasia of cytotrophoblastic
      cells only in uterine torsion and hydroallantois cases. In conclusion, NO level
      and CTUP can be used as indicators for pregnancy pathology that is usually
      associated with presence of cytotrophoblastic cells and placental insufficiency.

PMID- 27693012
TI  - Anti-Muellerian hormone, inhibin A, gonadotropins, and gonadotropin receptors in
      bull calves after partial scrotal resection, orchidectomy, and Burdizzo
      castration.
AB  - Eight-week-old calves were either castrated by partial scrotal resection (SR)
      without removing the testes (n = 10), Burdizzo (BZ) clamp (n = 10), orchidectomy
      (OR; n = 10), or were left gonad intact as controls (CO; n = 10). Concentrations
      of anti-Muellerian hormone (AMH), inhibin A, luteinizing hormone (LH), and
      follicle-stimulating hormone (FSH) in plasma were determined from 16 to 48 weeks
      of age. At 18 months, testes of SR, BZ, and CO bulls were obtained and the
      immunolocalization of LH and FSH receptors and AMH analyzed. Concentration of AMH
      in plasma of CO and SR bulls decreased with increasing age (P < 0.001). A similar
      AMH profile in CO and SR indicates that SR did not induce a true cryptorchid
      state. In groups OR and BZ, AMH was undetectable. Plasma inhibin concentration
      was higher in groups CO and SR than BZ and OR (P < 0.001). Plasma LH and FSH
      concentrations decreased over time (P < 0.001) and were higher in groups BZ and
      OR than SR and CO (P < 0.001). In the testes, immunolabeling for AMH existed in
      Sertoli cells of CO and SR but not BZ bulls. FSH receptors were localized in
      Sertoli cells, Leydig cells, spermatocytes, and the epididymis of CO and SR
      animals, whereas LH receptors were restricted to Leydig cells. In BZ animals, FSH
      and LH receptors and AMH were absent, indicating complete testicular
      degeneration. In conclusion, AMH is a more reliable marker for the presence of
      testicular tissue in bulls than inhibin. Scrotal resection did not induce a true
      inguinal cryptorchid state but affected testicular responsiveness to gonadotropic
      stimulation.

PMID- 27693013
TI  - Proposed breakpoint of piperacillin/tazobactam against extended spectrum beta
      lactamases producing bacteria in bacteremia.
AB  - The isolation rate of extended-spectrum beta-lactamase (ESBL)-producing bacteria
      have been increasing in Japan. While the efficacy of piperacillin/tazobactam
      (PIPC/TAZ) for ESBL-producing bacteria is controversial, carbapenems have
      generally been shown to be effective. The aim of this study was to determine
      whether the current Clinical and Laboratory Standards Institute susceptibility
      breakpoint of <=16/4 MUg/mL PIPC/TAZ predicts the clinical usefulness for
      bacteremia caused by ESBL-producing Enterobacteriaceae. We retrospectively
      investigated 35 patients with bacteremia caused by Enterobacteriaceae producing
      ESBLs treated with PIPC/TAZ monotherapy. The microbiological and clinical
      efficacy with PIPC/TAZ minimum inhibitory concentrations (MICs) of <=16/4 MUg/mL
      was better than that with MICs >= 32/4 MUg/mL. In contrast, MICs <=8/4 MUg/mL
      showed significantly higher microbiological and clinical efficacy compared to
      that of MICs >=16/4 MUg/mL (P < 0.05). These results suggest that 8/4 MUg/mL
      PIPC/TAZ MIC is recommended as a breakpoint for bacteremia caused by ESBL
      producing Enterobacteriaceae in Japan, although the current CLSI breakpoint is
      also useful.

PMID- 27693014
TI  - Effectiveness of weekly polymerase chain reaction-based open reading frame typing
      analysis of all newly isolated methicillin-resistant Staphylococcus aureus
      strains for controlling nosocomial infections.
AB  - Polymerase chain reaction (PCR)-based open reading frame typing (POT) helps
      differentiate between bacterial strains based on the open reading frames (ORFs)
      of the prophage-encoding genes; multiplex PCR screening is performed to identify
      strains based on keeping patterns. At our hospital, surveillance of nosocomial
      methicillin-resistant Staphylococcus aureus (MRSA) transmission is undertaken
      using POT to conduct molecular epidemiological analysis for all newly detected
      MRSA strains. In 2014, we performed POT only once a month; however, in 2015, we
      increased the frequency of POT to once a week, which helped us detect nosocomial
      transmission that would normally be difficult to detect, and thus achieve 40%
      reduction in nosocomial transmission, compared to that in 2014. This suggests
      that weekly POT screening for all MRSA strains is one of the effective methods
      available for minimizing nosocomial transmission of MRSA.

PMID- 27693015
TI  - Silver bonded to silica gel applied to the separation of polycyclic aromatic
      sulfur heterocycles in heavy gas oil.
AB  - Silica gel containing silver ions was prepared and characterized. Silica was
      organofunctionalized with 3-mercaptopropyl group by using grafting reaction
      followed by silver ions adsorption (silver covalently bonded to mercaptopropyl
      silca gel, Ag-MPSG). The organofunctionalization and silver coordination were
      observed by transmission infrared spectroscopy and elemental analyses (CHN and
      EDS). The textural characteristics were studied by N2 adsorption-desorption
      isotherms. Additionally, optical properties were studied by diffuse reflectance
      spectroscopy. The Ag-MPSG material was employed as stationary phase for the first
      time for fractionation of a heavy gas oil sample resulting in a fraction that is
      richer in polycyclic aromatic sulfur heterocycles (PASH). The fractions were
      analyzed by comprehensive two-dimensional gas chromatography with time-of-flight
      mass spectrometric detector and Ag-MPSG material provided similar fractionation
      performance when compared to conventional material [palladium covalently bonded
      to mercaptopropyl silca gel, Pd(II)-MPSG] usually employed for the same purpose
      and as the cost of silver is less than the one of palladium, the cost of the
      fractionation phase was reduced.

PMID- 27693016
TI  - Graphene oxide framework: An adsorbent for solid phase extraction of phenylurea
      herbicides from water and celery samples.
AB  - 1,4-Phenyldiboronic acid (1,4-PDBA) linked graphene oxide framework (GOF) was
      prepared via an one-step, catalyst-free and hydrothermal route. To evaluate its
      adsorption performance, the prepared GOF was served as an adsorbent for solid
      phase extraction of phenylurea herbicides (PUHs) from water and celery samples
      prior to their determination by high performance liquid chromatography. The
      results indicated that GOF exhibited excellent adsorption capacity for the target
      PUHs. Under the optimum conditions, the method showed high recoveries ranged from
      86.0% to 112.0%, low relative standard deviations (<5.4%) and low limits of
      detection ranged from 0.01 to 0.02ngmL-1 for water and 0.025-0.050ngg-1 for
      celery sample, respectively. These results indicated the great application
      potential of GOF in the enrichment of organic pollutants from different matrix
      samples.

PMID- 27693017
TI  - Standardized bovine colostrum derivative impedes development of type 1 diabetes
      in rodents.
AB  - Bovine colostrum is a rich source of nutrients and immunologically active
      components that play a role in conveying passive immunity to the offspring,
      protection and maturation of new-born's gastrointestinal tract. Colostrum has
      exerted positive effects in diseases affecting gastrointestinal tract, as well as
      type 2 diabetes (T2D). However, health-promoting effects in type 1 diabetes have
      not been reported. The aim of this study was to investigate therapeutic value of
      oral administration of standardized bovine colostrum derivative (SBCD) in three
      models of type 1 diabetes (T1D): spontaneously developed T1D in NOD mice and BB
      DP rats, and in chemically induced T1D in C57BL/6 mice with multiple low doses of
      streptozotocin (MLDS). SBCD was administered per os and the disease development
      was evaluated by weekly measurement of blood glucose and by histological analyses
      of the pancreas. SBCD administration prevented diabetes development in all three
      models, as indicated by euglicaemia. Ex vivo analysis of cytokine expression and
      production in the spleen and mesenteric lymph nodes (MLN) in MLDS challenged mice
      revealed a strong modulation of the immune response. In the MLN cells SBCD
      disrupted harmful Th17 response induced by MLDS. Expression of Th1 signature
      cytokine IFN-gamma was down-regulated in MLN cells of SBCD-treated mice, while IL
      4 secretion (Th2 cytokine) was up-regulated in comparison to diabetic group.
      Modulation of the immune response seen in the MLN protruded to the spleen, giving
      overall less infiltration of immune cells to the pancreas. SBCD acted on immune
      cells and halted (auto) aggression towards pancreatic beta cells. Moreover, SBCD
      induced beta cell proliferation. Hence, this derivative could be tested in
      diabetes and other similar diseases with aberrant immune response.

PMID- 27693018
TI  - A vaccine composed of a hypothetical protein and the eukaryotic initiation factor
      5a from Leishmania braziliensis cross-protection against Leishmania amazonensis
      infection.
AB  - In the present study, two proteins cloned from Leishmania braziliensis species, a
      hypothetical protein (LbHyp) and the eukaryotic initiation factor 5a (EiF5a),
      were evaluated to protect BALB/c mice against L. amazonensis infection. The
      animals were immunized with the antigens, either separately or in combination,
      using saponin as an immune adjuvant in both cases. Spleen cells from vaccinated
      and later infected mice produced significantly higher levels of protein and
      parasite-specific IFN-gamma, IL-12, and GM-CSF, in addition to low levels of IL-4
      and IL-10. Evaluating the parasite load by means of a limiting dilution technique
      and quantitative Real-Time PCR, vaccinated animals presented significant
      reductions in the parasite load in both infected tissues and organs, as well as
      lower footpad swelling, when compared to the control (saline and saponin) groups.
      The best results regarding the protection of the animals were achieved when the
      combined vaccine was administered into the animals. Protection was associated
      with an IFN-gamma production against parasite antigens, which was mediated by
      both CD4+ and CD8+ T cells and correlated with antileishmanial nitrite
      production. In conclusion, data from the present study show that this polyprotein
      vaccine, which combines two L. braziliensis proteins, can induce protection
      against L. amazonensis infection.

PMID- 27693019
TI  - Enzyme-linked immunosorbent assays for detection of anti-transcriptional
      intermediary factor-1 gamma and anti-Mi-2 autoantibodies in dermatomyositis.
AB  - BACKGROUND: Autoantibodies against transcriptional intermediary factor 1 (TIF1)
      and Mi-2 are selectively detected in patients with dermatomyositis (DM). To
      measure these antibodies readily, the development of reliable ELISA systems has
      been needed. OBJECTIVE: This study aimed to establish enzyme-linked immunosorbent
      assays (ELISAs) for anti-TIF1gamma and anti-Mi-2beta antibodies (Abs) and to
      assess their utility. METHODS: Serum samples were obtained from 104 patients with
      classic DM, 68 with clinically amyopathic DM (CADM) and 70 with polymyositis, who
      were followed up at 8 medical centers across Japan. Serum samples from 190
      patients with other connective tissue diseases (CTDs) and 123 healthy individuals
      were also assessed. Serum antibody levels were examined by ELISAs coated with
      full-length TIF1gamma or Mi-2beta proteins produced by a baculovirus expression
      system. To assess the cross-reactivity, partial-length Mi-2beta proteins with or
      without mutations were produced and examined for reactivity. RESULTS: When
      compared with immunoprecipitation assay, anti-TIF1gamma Ab ELISA showed 100%
      sensitivity and 100% specificity, while anti-Mi-2beta Ab ELISA showed 100%
      sensitivity and 99.6% specificity. Anti-TIF1gamma Ab was positive in 30 (28.8%)
      with classic DM and 4 (5.9%) with CADM, whereas 14 (13.5%) with classic DM, but
      none with CADM, were positive for anti-Mi-2beta Ab. Of 30 anti-TIF1gamma Ab
      positive DM patients, 23 (67.6%) had malignancy. Anti-Mi-2beta Ab-positive serum
      samples exhibited modest cross-reactivity with the TIF1gamma protein due to the
      homologous amino acid sequence containing cysteines in their plant homeodomains.
      CONCLUSION: The current study demonstrates the utility of newly established
      ELISAs for anti-TIF1gamma and anti-Mi-2beta Abs, which can serve as easier
      detection systems for routine testing.

PMID- 27693020
TI  - Novel lipopeptides of ESAT-6 induce strong protective immunity against
      Mycobacterium tuberculosis: Routes of immunization and TLR agonists critically
      impact vaccine's efficacy.
AB  - Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a
      leading infectious agent worldwide. The development of a new vaccine against Mtb
      is essential to control global spread of tuberculosis, since the current vaccine
      BCG is not very effective and antibiotic resistance is a serious, burgeoning
      problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been
      implicated in inducing protective immunity against Mtb. Peptide based subunit
      vaccines are attractive due to their safety and high specificity in eliciting
      immune responses, but small synthetic peptides are usually not very immunogenic.
      We have designed a novel subunit vaccine for Mtb by using simple lipid (palmitic
      acid) modified derivatives of peptides from ESAT-6 protein corresponding to
      dominant human T cell epitopes and examined their ability to stimulate protective
      immunity against Mtb by intranasal and subcutaneous immunization in mice. We also
      investigated how individual TLR agonists as adjuvants (PolyI:C, MPL and GDQ)
      contribute to enhancing the induced immune responses and resulting protective
      efficacy of our vaccine. We observed that single C-terminal palmitoyl-lysine
      modified lipopeptides derived from ESAT-6 induce significant cellular immune
      responses on their own upon mucosal and subcutaneous immunizations. Intriguingly,
      a combination of immunogenic lipopeptides of ESAT-6 antigen exhibited local
      (pulmonary) and systemic immune responses along with efficient protective
      efficacy when administered intranasally or subcutaneously. Surprisingly,
      combination of ESAT-6 derived lipopeptides with a TLR-4 agonist (MPL) enhanced
      protection, whereas TLR-3 (Poly I:C) and TLR-7/8 agonists (gardiquimod, GDQ) led
      to reduced protection associated with specific local and systemic immune
      modulation. Our studies demonstrate the potential of ESAT-6 derived lipopeptides
      as a promising vaccine candidate against Mtb, and emphasize that selection of
      adjuvant is critical for the success of vaccines. These findings demonstrate the
      promise of synthetic lipopeptides as the basis of a subunit vaccine for TB.

PMID- 27693021
TI  - Adipofascial fold-down flaps based on the posterior tibial artery perforator to
      cover the medial foot and ankle defects.
AB  - PURPOSE: We report the clinical outcome after coverage for soft-tissue defect on
      the medial foot and ankle with an adipofascial fold-down flap based on the
      posterior tibial artery perforator branch proximal to the defect. MATERIALS: Nine
      patients (five males and four females) with soft-tissue defects on the medial
      foot and ankle area underwent the procedure from March 2009 to May 2014. The
      average age of the patients was 54 years (range, 8-82). The pivot point of
      transposition of this flap is the posterior tibial artery perforator proximal to
      the defect. Therefore, the adiposal side of this flap was folded down to
      resurface the defect. The donor site was closed primarily with the preserved skin
      flap. The skin graft to the flap was delayed until the flap became mature. The
      difference between the circumferences of both ankles was measured. RESULTS: All
      flaps survived and adequate soft-tissue coverage was obtained for the medial foot
      and ankle after the skin graft. Wearing normal footwear was possible for all
      patients because of thin coverage of the flaps. No secondary debulking procedure
      was performed for the patients. The difference between the circumferences of both
      sides of the ankle was not significant. The skin necrosis of the donor site was
      also managed conservatively and healed well. CONCLUSION: For the medial foot and
      ankle soft-tissue defect, the fold-down adipofascial flaps based on the posterior
      tibial artery perforator branch proximal to the defect could be a good option to
      cover it.

PMID- 27693022
TI  - Investigating the effects of non-vascularized free fat transplantation and cell
      assisted lipotransfer in vivo: A useful animal model.

PMID- 27693024
TI  - Calcium Subtraction: A New Horizon for Cardiac CT?

PMID- 27693025
TI  - Concomitant Rivaroxaban and Dronedarone Administration in Patients With
      Nonvalvular Atrial Fibrillation.

PMID- 27693023
TI  - A Single-Cell Transcriptome Atlas of the Human Pancreas.
AB  - To understand organ function, it is important to have an inventory of its cell
      types and of their corresponding marker genes. This is a particularly challenging
      task for human tissues like the pancreas, because reliable markers are limited.
      Hence, transcriptome-wide studies are typically done on pooled islets of
      Langerhans, obscuring contributions from rare cell types and of potential
      subpopulations. To overcome this challenge, we developed an automated platform
      that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes
      of thousands of single pancreatic cells from deceased organ donors, allowing in
      silico purification of all main pancreatic cell types. We identify cell type
      specific transcription factors and a subpopulation of REG3A-positive acinar
      cells. We also show that CD24 and TM4SF4 expression can be used to sort live
      alpha and beta cells with high purity. This resource will be useful for
      developing a deeper understanding of pancreatic biology and pathophysiology of
      diabetes mellitus.

PMID- 27693028
TI  - Discussion.

PMID- 27693026
TI  - Hemoptysis in a Patient with Elevated Immunoglobulin E.
AB  - Recurrent pneumonia with cavitation leading to pneumatoceles, secondary fungal
      infections, and hemoptysis are major causes of mortality and morbidity in
      patients with hyper-IgE syndrome. Prevention and aggressive treatment of
      pneumonia in these patients are essential to prevent further lung damage, but
      treatment may be delayed because the classic signs/symptoms of infection such as
      fever, chills, or rigors may be lacking. Early imaging to identify infection is
      essential for diagnosis and treatment. The mainstay of therapy is continuous,
      full-dose daily trimethoprim-sulfamethoxazole and commonly fungal coverage.
      Because hyper-IgE syndrome is a progressive disease, patients' condition may
      worsen despite compliance with prophylactic therapy.

PMID- 27693029
TI  - Iliofemoral endarterectomy associated with systematic iliac stent grafting for
      the treatment of severe iliofemoral occlusive disease.
AB  - OBJECTIVE: Iliofemoral endarterectomy with external iliac artery (EIA) stent
      grafting can be an alternative to traditional open surgery in patients with
      severe iliac occlusive disease extending to the common femoral artery. We report
      the midterm outcomes of this approach. METHODS: Between 2009 and 2015, 108
      patients (76% male; median age, 63 years) underwent a total of 127 iliofemoral
      endarterectomies combined with EIA stent grafting. Indications were claudication
      in 60%, rest pain in 20%, ulceration in 15%, and acute ischemia in 5%. Lesions
      exclusively involved only the EIA segment in 40% of cases, with occlusion in 28%.
      Lesions involved both the EIA and common iliac artery segments in 49% of cases,
      with 19% of common iliac artery occlusions and 24% of EIA occlusions. Iliac
      lesions extended into the aortic segment in 11% of cases. Iliofemoral
      endarterectomy was performed by eversion whenever possible. Deployment of the EIA
      stent graft systematically incorporated the EIA segment and the proximal end of
      the endarterectomy. Self-expanding covered stents were calibrated to the diameter
      of the endarterectomized EIA. RESULTS: The procedure was technically successful
      in 100% of patients. Median diameter of covered stents was 8 mm (range, 6-10 mm).
      No intraoperative arterial rupture or dissection was observed. Early reoperations
      (3%) were performed for bleeding, infection, or thrombosis. Median length of stay
      was 5 days. No 30-day mortality was observed. Median follow-up was 30 months
      (range, 0-6 years), and overall mortality was 13% (due to cancer in half of the
      cases). Repeated angioplasty was performed in three (2%) cases, and a subsequent
      open procedure on the iliofemoral segment was performed in seven (5%) cases. At 2
      years, primary patency rate of the treated segment was 91%. The 2-year primary
      assisted patency and secondary patency rates were 94% and 98%, respectively. Five
      year primary, primary assisted, and secondary patency rates were 87%, 92%, and
      98%, respectively. CONCLUSIONS: Combined iliofemoral endarterectomy and covered
      stenting of the EIA for treatment of severe occlusive lesions provided acceptable
      midterm results, probably because of the gain of diameter provided by covered
      stents. This technique avoids complications due to an aortic or iliac surgical
      approach and clamping as well as complications related to the presence of a
      prosthetic implant in an intra-abdominal position.

PMID- 27693027
TI  - Diagnostic performance of 320-slice computed tomography coronary angiography for
      symptomatic patients in clinical practice.
AB  - OBJECTIVE: Multi-slice computed tomography (MSCT) coronary angiography has been
      reported as an effective alternative to invasive conventional coronary
      angiography (CCA) for the diagnosis of coronary artery disease (CAD). However, in
      previous reports, the diagnostic accuracy of MSCT has not been significant enough
      to be of benefit in symptomatic patients. The aim of this study was to identify
      the usefulness of 320-slice computed tomography coronary angiography (320-CTA)
      for symptomatic patients in terms of the diagnostic accuracy of 320-CTA and the
      prevalence of vasospastic angina pectoris (VSAP) within the study cohort.
      METHODS: We retrospectively analyzed 513 consecutive symptomatic patients with
      suspected CAD who had undergone 320-CTA and CCA. We determined the diagnostic
      accuracy of 320-CTA using CCA as the reference standard. Ergonovine provocation
      tests were performed on patients without significant coronary artery stenosis on
      CCA. RESULTS: Of the total cohort of 513 symptomatic patients, 39% had
      obstructive CAD. The patient based analysis of the accuracy of 320-CTA showed a
      sensitivity of 91.0%, a specificity of 71.0%, a positive predictive value of
      66.5%, and a negative predictive value of 92.5%. Of the 314 symptomatic patients
      who did not have significant coronary artery stenosis on CCA, 58 (18%) were
      diagnosed with VSAP using ergonovine provocation tests. DISCUSSION: The negative
      and positive predictive values indicate that 320-CTA cannot replace CCA for
      symptomatic patients. Indeed, a combination of CCA and ergonovine provocation
      tests should be taken into consideration for symptomatic patients.

PMID- 27693030
TI  - Shear accumulation as a means for evaluating risk of thromboembolic events in
      novel endovascular stent graft designs.
AB  - OBJECTIVE: This study proposes to establish a simulation-based technique for
      evaluating shear accumulation in stent grafts and to use the technique to assess
      the performance of a novel branched stent graft system. METHODS: Computational
      fluid dynamics models, with transient boundary conditions, particle injection,
      and rigid walls, simplifying assumptions were developed and used to evaluate the
      shear accumulation in various stent graft configurations with a healthy aorta as
      comparison. RESULTS: Shear streamlines are presented for the various
      configurations. Shear accumulation was also calculated for each configuration.
      The number of particles with shear accumulations >3.5 Pa-s for each configuration
      was compared with the shear accumulation values of commercially available
      mechanical aortic valves from the literature. CONCLUSIONS: The stent graft
      configuration with the diaphragm does have particles with shear accumulation >3.5
      Pa-s. However, the percentage of particles with shear accumulation above 3.5 Pa-s
      is less than the two commercially available mechanical aortic valves, and more
      surprisingly, is smaller than in the healthy aorta.

PMID- 27693031
TI  - Initial in vitro and in vivo evaluation of a self-monitoring prosthetic bypass
      graft.
AB  - OBJECTIVE: Prosthetic grafts used for lower extremity revascularization and
      dialysis access fail because of hyperplastic stenosis and thrombosis. Graft
      surveillance is advocated to monitor function; however, graft failure can occur
      between episodic examinations. An innovative sensor with wireless, microchip
      technology allows automated surveillance with assessment of graft function using
      a "cloud"-based algorithm. We performed proof-of-concept experiments with in
      vitro and in vivo models to assess the feasibility such a real-time graft
      surveillance system. METHODS: A self-monitoring graft system was evaluated
      consisting of a prosthetic conduit of expanded polytetrafluoroethylene and a
      sensor unit, and a microsensor, microelectronics, battery, and remote processor
      with a monitor. The sensor unit was integrated on the extraluminal surface of
      expanded polytetrafluoroethylene grafts without compromise to the lumen of the
      conduit. The grafts were tested in vitro in a pulsatile, recirculating flow
      system under physiologic flow parameters. The hemodynamic parameters were varied
      to assess the ability to obtain wireless signal acquisition reflecting real-time
      flow properties in vitro. Segments of custom tubing with reduced diameters were
      inserted into the model to mimic stenosis proximal and distal to the grafts.
      After characterization of the initial data, the self-monitoring grafts were
      implanted in an ovine carotid model to assess proof of concept in vivo with 30
      day follow-up of signal acquisition as well as arteriographic and histologic
      analysis. RESULTS: In vitro flow data demonstrated the device was able to
      determine factors related to prosthetic graft function under varied hemodynamic
      flow conditions. Wireless signal acquisition using Bluetooth technology
      (Bluetooth SIG, Inc, Kirkland, Wash) allowed remote data analysis reflecting
      graft flow parameters through changes in microsensor voltage and frequency.
      Waveform analysis was applied to construct an algorithm using proprietary
      software and determine a parameter for graft flow characteristics. This algorithm
      allowed determination of the degree of stenosis and location of stenosis location
      (proximal or distal) for display on a remote monitor in real time. Subsequent in
      vivo experiments confirmed the ability of the system to generate signal
      acquisition through skin and soft tissue under biologic conditions with no
      arteriographic stenosis and a favorable healing response at 30-day harvest.
      CONCLUSIONS: Initial in vitro and in vivo experiments demonstrate the ability for
      a self-monitoring graft system to remotely monitor hemodynamic parameters
      reflecting graft function using wireless data transmission. This automated system
      shows promise to deliver real-time data that can be analyzed by cloud-based
      algorithms alerting the clinician of a change in graft function or development of
      stenosis for further diagnostic study or intervention before graft failure.

PMID- 27693034
TI  - A systematic review of concept mapping dissertations.
AB  - The purpose of this study was to identify, summarize, and synthesize all doctoral
      dissertations completed using Trochim's concept mapping methodology between 1985
      and 2014. A comprehensive search produced a set of 108 eligible dissertations; of
      which 104 were available as full-text or hard copy. The studies were coded on 77
      variables, which were summarized in descriptive analyses. The dissertations were
      conducted in a wide variety of topic areas and completed at 35 different
      universities in the US and Canada. On comparable variables, the results were
      similar to two prior syntheses (Trochim, 1993; Rosas & Kane, 2012). The mean
      multidimensional scaling analysis stress value for 96 concept maps was 0.26 with
      a standard deviation of 0.05. Cumulative rates of dissertation completion and
      resulting citations of the dissertations and any resulting articles were plotted
      over the study period. Reliability and validity were considered in most studies
      but formally assessed in a minority of cases. The review concludes with a summary
      of findings and thoughts about future studies.

PMID- 27693032
TI  - An endovascular model of ischemic myopathy from peripheral arterial disease.
AB  - OBJECTIVE: Peripheral arterial disease (PAD) is a significant age-related medical
      condition with limited pharmacologic options. Severe PAD, termed critical limb
      ischemia, can lead to amputation. Skeletal muscle is the end organ most affected
      by PAD, leading to ischemic myopathy and debility of the patient. Currently,
      there are not any therapeutics to treat ischemic myopathy, and proposed biologic
      agents have not been optimized owing to a lack of preclinical models of PAD.
      Because a large animal model of ischemic myopathy may be useful in defining the
      optimal dosing and delivery regimens, the objective was to create and to
      characterize a swine model of ischemic myopathy that mimics patients with severe
      PAD. METHODS: Yorkshire swine (N = 8) underwent acute right hindlimb ischemia by
      endovascular occlusion of the external iliac artery. The effect of ischemia on
      limb function, perfusion, and degree of ischemic myopathy was quantified by
      weekly gait analysis, arteriography, hindlimb blood pressures, femoral artery
      duplex ultrasound scans, and histologic examination. Animals were terminated at 5
      (n = 5) and 6 (n = 3) weeks postoperatively. Ossabaw swine (N = 8) fed a high-fat
      diet were used as a model of metabolic syndrome for comparison of arteriogenic
      recovery and validation of ischemic myopathy. RESULTS: There was persistent
      ischemia in the right hindlimb, and occlusion pressures were significantly
      depressed compared with the untreated left hindlimb out to 6 weeks (systolic
      blood pressure, 31 +/- 21 vs 83 +/- 15 mm Hg, respectively; P = .0007). The blood
      pressure reduction resulted in a significant increase of ischemic myopathy in the
      gastrocnemius muscle in the treated limb. Gait analysis revealed a functional
      deficit of the right hindlimb immediately after occlusion that improved rapidly
      during the first 2 weeks. Peak systolic velocity values in the right common
      femoral artery were severely diminished throughout the entire study (P < .001),
      and the hemodynamic environment after occlusion was characterized by low and
      oscillatory wall shear stress. Finally, the internal iliac artery on the side of
      the ischemic limb underwent significant arteriogenic remodeling (1.8* baseline)
      in the Yorkshire but not in the Ossabaw swine model. CONCLUSIONS: This model uses
      endovascular technology to produce the first durable large animal model of
      ischemic myopathy. Acutely (first 2 weeks), this model is associated with
      impaired gait but no tissue loss. Chronically (2-6 weeks), this model delivers
      persistent ischemia, resulting in ischemic myopathy similar to that seen in PAD
      patients. This model may be of use for testing novel therapeutics including
      biologic therapies for promoting neovascularization and arteriogenesis.

PMID- 27693033
TI  - [Potentially inappropriate prescribing in older Spanish population according to
      STOPP/START criteria (STARTREC study)].
AB  - OBJECTIVE: Rational prescribing in older people is a priority for health care
      organizations. The STOPP/START screening tool has been developed to identify
      potentially inappropriate prescribing (PIP) in individuals. In a primary care
      setting, STOPP/START can estimate PIP prevalence and related factors at
      population level. The aim of this study is to measure the prevalence rates of PPI
      in elderly population using clinical and prescription claim databases. DESIGN:
      Cross-sectional population study. SETTINGS: Primary Care, Lleida Health Region,
      Spain. PARTICIPANTS: 45.408 patients 70 years old and over, attended in the
      primary health care centers at least once the last year. METHODS: 43 STOPP and 12
      START criteria are applied to their 2012 clinical and prescription records.
      Logistic regression models are adjusted to determine PIP association with several
      factors. RESULTS: 45,408 patients are included. The mean age is 79.7 years, 58%
      being female. The overall prevalence of PPI is 58.1%. According to STOPP, the
      most common drugs identified are benzodiazepines, non-steroidal anti-inflammatory
      drugs and proton pump inhibitors; according to START, osteoporosis treatments,
      antiplatelet agents, statins, metformin and beta blockers. PIP increases with age
      and polypharmacy and it is higher in long-term care facilities residents and
      patients receiving home health care. CONCLUSIONS: In our Health Region, at least
      50% of the population aged 70 or older has one or more PIP, according to
      STOPP/START criteria.

PMID- 27693035
TI  - [Same-day discharge for robot-assisted hysterectomy with sentinel node biopsy:
      Are we ready in France?]

PMID- 27693036
TI  - The lncRNA H19 interacts with miR-140 to modulate glioma growth by targeting
      iASPP.
AB  - H19, one of the first found cancer-associated long non-coding RNAs (lncRNAs), is
      involved in the development and progression of many types of tumors. An aberrant
      expression of H19 was observed in hepatocellular carcinoma, cervical cancer,
      breast cancer, ovarian cancer, and colorectal cancer. However, the exact effects
      and molecular mechanisms of H19 in glioma progression are still unknown up to
      now. In this study, we investigated the role of H19 in human glioma cell lines
      and clinical tumor samples in order to determine the function of this molecule.
      In our research, lncRNA-H19 was specifically upregulated in glioma cell lines and
      promoted glioma cell growth through targeting miR-140. Knockdown of H19 inhibited
      the proliferation and invasion of human glioma cell and suppressed its metastasis
      in vitro and in vivo. In addition, miR-140 dependent inhibitor of apoptosis
      stimulating protein of p53 (iASPP) regulation was required in H19 induced glioma
      cell growth. These findings indicated that H19 might regulate the tumor growth
      and metastasis via miR-140 dependent iASPP regulation. Taken together, our data
      indicated that H19 might be an oncogenic lncRNA that promoted proliferation and
      metastasis of glioma and could be regarded as a therapeutic target in human
      glioma.

PMID- 27693038
TI  - High-fat diet feeding promotes stemness and precancerous changes in murine
      gastric mucosa mediated by leptin receptor signaling pathway.
AB  - Obesity increases the risk for gastric cancers. However, the occurrence and
      mechanisms of precancerous atrophic gastritis induced by high-fat diet (HFD)
      remain unclear. Here, we show that HFD-associated lipotoxicity induces
      precancerous lesions that are accompanied by the disruption of organelle
      homeostasis, tissue integrity, and deregulated expression of stemness genes in
      the gastric epithelium mediated by leptin receptor (ObR) signaling. Following HFD
      feeding, ectopic fat accumulated and expression of LAMP2A in lysosome and COX IV
      in mitochondria increased in the gastric mucosa. HFD feeding also led to enhanced
      expression of activated-Notch1 and stem cell markers Lgr5, CD44, and EpCAM. In
      addition, HFD-fed mice showed intracellular beta-catenin accumulation in the
      gastric mucosa with increased expression of its target genes, Nanog, Oct4, and c
      Myc. These observations were abrogated in the leptin-deficient ob/ob mice and ObR
      mutated db/db mice, indicating that these HFD-induced changes were responsible
      for effects downstream of the ObR. Consistent with this, the expression of the
      Class IA and III PI3Ks was increased following ObR activation in the gastric
      mucosa of HFD-fed mice. Together, these results suggest that HFD-induced
      lipotoxicity and deregulated organelle biosynthesis confer cancer stem cell-like
      properties to the gastric mucosa via signaling pathway mediated by leptin, PI3K
      and beta-catenin.

PMID- 27693037
TI  - Protein cysteine oxidation in redox signaling: Caveats on sulfenic acid detection
      and quantification.
AB  - Oxidation of critical signaling protein cysteines regulated by H2O2 has been
      considered to involve sulfenic acid (RSOH) formation. RSOH may subsequently form
      either a sulfenyl amide (RSNHR') with a neighboring amide, or a mixed disulfide
      (RSSR') with another protein cysteine or glutathione. Previous studies have
      claimed that RSOH can be detected as an adduct (e.g., with 5,5
      dimethylcyclohexane-1,3-dione; dimedone). Here, kinetic data are discussed which
      indicate that few proteins can form RSOH under physiological signaling
      conditions. We also present experimental evidence that indicates that (1)
      dimedone reacts rapidly with sulfenyl amides, and more rapidly than with sulfenic
      acids, and (2) that disulfides can react reversibly with amides to form sulfenyl
      amides. As some proteins are more stable as the sulfenyl amide than as a
      glutathionylated species, the former may account for some of the species
      previously identified as the "sulfenome" - the cellular complement of reversibly
      oxidized thiol proteins generated via sulfenic acids.

PMID- 27693039
TI  - Real-time monitoring of artemin in vivo chaperone activity using luciferase as an
      intracellular reporter.
AB  - Artemin is an abundant thermostable protein in Artemia encysted embryos and
      considered as a stress protein, as its highly regulated expression is associated
      with stress resistance. Artemin cDNA was previously isolated and cloned from
      Artemia urmiana and artemin was found as an efficient molecular chaperone in
      vitro. Here, co-transformation of E. coli was performed with two expression
      vectors containing artemin and firefly luciferase for in vivo studies. The time
      course of luciferase inactivation at low and elevated temperatures showed that
      luciferase was rapidly inactivated in control cells, but it was found that
      luciferase was protected significantly in artemin expressing cells. More
      interestingly, luciferase activity was completely regained in heat treated
      artemin expressing cells at room temperature. In addition, in both stress
      conditions, similar to residual activity of luciferase, cell viability in induced
      cultures over-expressing artemin was significantly higher than non-expressed
      artemin cells. It can be suggested that artemin confers impressive resistance in
      stressful conditions when introduced into E. coli cells, which is due to that it
      protects proteins against aggregation. Such luciferase co-expression system can
      be used as a real-time reporter to investigate the activity of chaperone proteins
      in vivo and provide a rapid and simple test for molecular chaperones.

PMID- 27693040
TI  - miR-634 exhibits anti-tumor activities toward hepatocellular carcinoma via Rab1A
      and DHX33.
AB  - Deregulation of microRNAs contributes to the aberrant growth of hepatocellular
      carcinoma (HCC). Here, we showed that miR-634 expression was frequently decreased
      in HCC. Low miR-634 expression was significantly associated with larger tumor
      size, poorer tumor differentiation, advanced TNM stage, vascular invasion,
      absence of tumor capsule and unfavorable overall survival. Overexpression of miR
      634 markedly attenuated cell viability, colony formation, tumor growth and
      metastasis, whereas miR-634 inhibition resulted in the opposite phenotypes.
      Furthermore, re-introduction of miR-634 induced cell apoptosis in vitro and in
      vivo. Mechanistically, miR-634 inhibited the expression of Rab1A and DHX33 via
      directly binding to the 3'-UTR of both genes. In clinical samples, the expression
      of Rab1A or DHX33 was reversely correlated with miR-634. Re-expression of Rab1A
      or DHX33 abrogated the miR-634-mediated inhibition of cell proliferation and
      migration. Collectively, our data suggest a tumor suppressor role of miR-634 in
      HCC. The newly identified miR-634/Rab1A or miR-634/DHX33 axis serves as a
      potential therapeutic target for the clinical management.

PMID- 27693041
TI  - Vibrio barjaei sp. nov., a new species of the Mediterranei clade isolated in a
      shellfish hatchery.
AB  - Seven isolates were obtained from different culture stages of carpet shell clam
      (Ruditapes decussatus) reared in a bivalve hatchery (Galicia, NW Spain). Three
      groups were differentiated by genotyping techniques and phenotypic profiles and
      representative trains were selected to further taxonomic studies. These strains
      were studied by a polyphasic approach and in basis of the phylogenetic analysis
      based on concatenated sequences of the five housekeeping genes ftsZ, gyrB, pyrH,
      recA and rpoA formed a tight group into the Mediterranei clade of the genus
      Vibrio. Percentages of genomic resemblance, including average nucleotide
      identity, in silico genome-to-genome comparison and wet DNA-DNA hybridization
      between the type strain and the closest relatives Vibrio mediterranei and Vibrio
      thalassae were below of the proposed boundaries for the definition of species.
      The novel isolates could be also differentiated from the related taxa on the
      basis of several phenotypic traits and fatty acid profiles. Results obtained
      support the description of a novel species into the Mediterranei clade, for which
      the name Vibrio barjaei sp. nov. is proposed, with strain 3062T (=CECT 9090T=CAIM
      1921TT=LMG 29358T) as the type strain.

PMID- 27693042
TI  - A summary of the influence of exogenous estrogen administration across the
      lifespan on the GH/IGF-1 axis and implications for bone health.
AB  - Bone growth, development, and remodeling are modulated by numerous circulating
      hormones. Throughout the lifespan, the extent to which each of the hormones
      impacts bone differs. Understanding the independent and combined impact of these
      hormones on controlling bone remodeling allows for the development of more
      informed decision making regarding pharmacology, specifically the use of hormonal
      medication, at all ages. Endocrine control of bone health in women is largely
      dictated by the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and
      the hypothalamic-pituitary-ovarian (HPO) axis. Growth hormone, secreted from the
      pituitary gland, stimulates cells in almost every tissue to secrete IGF-1,
      although the majority of circulating IGF-1 is produced hepatically. Indeed,
      systemic IGF-1 concentrations have been found to be correlated with bone mineral
      density (BMD) in both pre- and post-menopausal women and is often used as a
      marker of bone formation. Sex steroids produced by the ovaries, namely estradiol,
      mediate bone resorption through binding to estrogen receptors on osteoclasts and
      osteoblasts. Specifically, by increasing osteoclast apoptosis and decreasing
      osteoblast apoptosis, adequate estrogen levels prevent excessive bone resorption,
      which helps to explain the rapid decline in bone mass that occurs with the
      menopausal decrease in estrogen production. Though there are documented
      correlations between endogenous estrogen concentrations and GH/IGF-1 dynamics,
      this relationship changes across the lifespan as sex-steroid dynamics fluctuate
      and, possibly, as tissue responsiveness to GH stimulation decreases. Aside from
      the known role of endogenous sex steroids on bone health, the impact of exogenous
      estrogen administration is of interest, as exogenous formulations further
      modulate GH and IGF-1 production. However, the effect and extent of GH and IGF-1
      modulation seems to be largely dependent on age at administration and route of
      administration. Specifically, premenopausal women using combined oral
      contraceptive therapy (COC), post-menopausal women taking oral hormone therapy
      (HT), and both pre- and post-menopausal women using a transdermal form of
      estrogen therapy (COC or HT) demonstrate disparate GH/IGF-1 responses to
      exogenous estrogen. This review serves to summarize what is currently known
      regarding the influence of exogenous estrogen administration across the lifespan
      on the GH/IGF-1 axis and implications for bone health.

PMID- 27693043
TI  - Influence of design and clinical factors on the removal force ratio in tapered
      implant-abutment interfaces.
AB  - STATEMENT OF PROBLEM: A previous study investigated the effects of the preload
      and taper-angle mismatch in tapered implant systems on the removal force
      characteristics of the self-locking mechanism. The present study builds upon the
      previous one and introduces the effects of the time elapsed between insertion and
      removal and the presence of saliva in the implant-abutment interface as 2 new
      additional parameters. PURPOSE: The purpose of this in vitro study was to
      elucidate the influences of design and clinical parameters on the removal force
      for implant systems that use tapered interference fit (TIF) type connections by
      measuring the force needed to remove an abutment from an implant. MATERIAL AND
      METHODS: Ninety-six implants with tapered abutment-implant interfaces
      specifically built for an unreplicated factorial design were tested on a custom
      built workbench for removal force. Four levels were chosen for the preload, FP,
      and the taper mismatch Deltatheta; 3 levels for the wait time t; and 2 levels for
      the saliva presence s at the interface. A regression model was used based on
      physical reasoning and a theoretical understanding of the interface. A 4-way
      ANOVA was used to evaluate the influence of the main effects and interactions
      (alpha=.05). RESULTS: The experiments strongly indicated that preload, taper
      mismatch, and saliva presence are relevant variables in removal force. The wait
      time becomes important when its effect is evaluated along with the preload.
      CONCLUSIONS: The results of this study can be used for decision making in the
      design and use of TIF type systems. The study supports the use of artificial
      saliva in any implant design experiment because of its significance in the
      removal force of the abutment.

PMID- 27693044
TI  - [The adolescent abstainers: A risk group?]
AB  - OBJECTIVE: If abstinence from substance in adolescents may nowadays be regarded
      statistically as a deviant behavior, what is its significance from a
      developmental point of view? The aim of this article is to examine the mental
      health characteristics and the social integration of adolescent abstainers.
      METHODS: A comprehensive literature review of epidemiological studies including
      data on adolescent abstainers was conducted. RESULTS: Compared to the abundant
      literature devoted to adolescent substance abusers, few studies report data on
      adolescent abstainers. In addition, many methodological problems limit their
      interpretability and their comparison. However that may be, this body of work
      suggests that if abstinence may be due to something intrinsic about the
      individual (such as psychosocial adjustment difficulties, personality traits or
      gender), many other environmental factors (such as family background of
      temperance, cultural practices, upbringing or religion) may determine abstaining
      behavior. By this way, from a psychopathological angle, adolescent abstainers
      certainly constitute a more heterogeneous group than the adolescent substance
      abusers. Some of them are quite psychologically healthy, whereas others are more
      socially withdrawn and may suffer from emotional disorders. CONCLUSION: In terms
      of prevention, these data highlight the need for longitudinal prospective studies
      examining the psychosocial status of adolescent abstainers, their antecedents,
      their outcome and their motivations.

PMID- 27693045
TI  - Use of ECG-gated computed tomography, echocardiography and selective angiography
      in five dogs with pulmonic stenosis and one dog with pulmonic stenosis and
      aberrant coronary arteries.
AB  - Pulmonic stenosis (PS) is the most common congenital cardiac disease in dogs.
      Boxers and English bulldogs are among the most commonly affected breeds and also
      commonly associated with an aberrant coronary artery (CA). If an aberrant CA is
      suspected and balloon valvuloplasty indicated, an intra-operative angiography is
      recommended prior to the procedure. ECG-gated computed tomography (CT) can be
      used to screen for CA anomalies in a quick and minimally-invasive way (preventing
      side effects associated with selective catheter angiography) and allowing early
      planning of the procedure. The aim of this case series was to report CT findings
      associated with PS diagnosed by echocardiography. Our database was
      retrospectively searched for cases of dogs with PS diagnosed by echocardiography,
      where an ECG-gated CT was performed. A total of six cases were retrieved: all
      were diagnosed with severe PS. Four dogs had concurrent congenital defects: two
      dogs had a patent ductus arteriosus, one dog had a ventricular septal defect and
      an overriding aorta, one dog had an aberrant CA. Detailed CT findings of all
      cases were reported, including one case of a patent ductus arteriosus and an
      overriding aorta not identified by transthoracic echocardiography. In addition,
      an abnormal single left coronary ostium, with a pre-pulmonic right CA was
      described. In conclusion, despite echocardiography remaining the gold standard
      for diagnosis and assessment of PS, ECG-gated-CT angiography is a complementary
      diagnostic method that may provide additional relevant information, shorten
      surgery/anaesthesia time and reduce the amount of radiation to which the
      clinician is subjected.

PMID- 27693046
TI  - Glycerophosphodiesterase GDE2 Promotes Neuroblastoma Differentiation through
      Glypican Release and Is a Marker of Clinical Outcome.
AB  - Neuroblastoma is a pediatric embryonal malignancy characterized by impaired
      neuronal differentiation. A better understanding of neuroblastoma differentiation
      is essential for developing new therapeutic approaches. GDE2 (encoded by GDPD5)
      is a six-transmembrane-domain glycerophosphodiesterase that promotes embryonic
      neurogenesis. We find that high GDPD5 expression is strongly associated with
      favorable outcome in neuroblastoma. GDE2 induces differentiation of neuroblastoma
      cells, suppresses cell motility, and opposes RhoA-driven neurite retraction. GDE2
      alters the Rac-RhoA activity balance and the expression of multiple
      differentiation-associated genes. Mechanistically, GDE2 acts by cleaving (in cis)
      and releasing glycosylphosphatidylinositol-anchored glypican-6, a putative co
      receptor. A single point mutation in the ectodomain abolishes GDE2 function. Our
      results reveal GDE2 as a cell-autonomous inducer of neuroblastoma differentiation
      with prognostic significance and potential therapeutic value.

PMID- 27693048
TI  - Insight into the oligomeric structure of PORA from A. thaliana.
AB  - Light-dependent protochlorophyllide oxidoreductase (POR, E.C. 1.3.1.33) is a
      plant enzyme that directly needs light to conduct a biochemical reaction. In the
      present paper we confirmed that POR forms large oligomers in solution before
      binding of substrates. We carried out the research using different techniques:
      cross-linking, native gel electrophoresis and FRET measurements. Mass
      spectrometry analysis of the cross-link products provided the first structural
      data about the organisation of the oligomer of POR. The results indicated that
      the catalytic motifs of the adjacent subunits become close to each other upon
      binding of substrates. Moreover, we identified two mutations of POR that
      disturbed its oligomerisation properties: Delta85-88 and Delta240-270.
      Additionally, a complete loss of the catalytic activity was observed for the
      following mutations: Delta189-194, Delta240-270, Delta318-331 and Delta392-393.

PMID- 27693050
TI  - Circulating miRNA as fine regulators of the physiological responses to physical
      activity: Pre-analytical warnings for a novel class of biomarkers.
AB  - MicroRNAs are endogenous non-coding RNAs that post-transcriptionally regulate
      gene expression by specifically binding the target mRNA and by consequently
      inducing its degradation. miRNAs can be released into the circulation where they
      remain stable and they can be measured. Their changes reflect individual biologic
      adaptation to exposures to specific environmental conditions. As such,
      measurement of circulating microRNAs represents an opportunity to evaluate
      biologic changes associated with interventions such as exercise and diet.
      Physical activity is, indeed, a very important modifying factor for circulating
      miRNAs. Toward their use in clinical settings several issues should be still
      solved. Their clinical application is hindered by the high heterogeneity of the
      analytical procedures used for their measurements. Furthermore, several pre
      analytical concerns equally reduce the clinical applicability of miRNA. Pre
      analytical phase in sports medicine is an important issue both because, often the
      conditions in which sampling are performed are peculiar (and not always
      canonical) and because some of the tested parameters, in the case of professional
      athletes, enters in routine anti-doping testing and, as such, they should be
      treated according to precise rules in order to avoid any false positive results.
      Aim of this review is to give an overview of the main available knowledges about
      the pre-analytical management of the sample for circulating miRNA evaluation
      along with the importance of miRNA as regulators of the response to physical
      activity and their possible future use in anti-doping settings.

PMID- 27693049
TI  - The antiangiogenic and antitumor activities of the N-terminal fragment of
      endostatin augmented by Ile/Arg substitution: The overall structure implicated
      the biological activity.
AB  - The antiangiogenic and antitumor activities of the 27-amino acid fragment
      corresponding to the N-terminal domain of endostatin were shown to be dependent
      on a Zn-binding loop in the N-terminus. To investigate whether the regions
      outside of the N-terminal loop play a role in the peptide function, the structure
      and function of a variant containing Ile26Arg mutation (ES-R) were compared with
      those of the native peptide (ES-Zn). Structural analysis using far-UV CD,
      intrinsic fluorescence and molecular dynamics simulation provided information
      regarding the overall changes upon the mutation. In addition, the docking
      simulations predicted a higher affinity of ES-R to integrins alphavbeta3 and
      alpha5beta1 than ES-Zn and a profound reorganization of the binding residues
      throughout the sequence. In Human Umbilical Vein Endothelial Cells (HUVECs), ES-R
      inhibited the tube formation and activated caspase-3 more strongly than do ES-Zn.
      Based on in vivo studies, the growth of breast tumor and expression of CD31, Bcl
      2 and nonfunctional p53 were inhibited more effectively by ES-R than by ES-Zn. We
      conclude that the C-terminal region is involved in the peptide function through
      some global structural effects.

PMID- 27693047
TI  - Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche
      Recapitulates Features of Early Gliomagenesis.
AB  - Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through
      neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this
      disease, we conditionally expressed Idh1R132H in the subventricular zone (SVZ) of
      the adult mouse brain. The mice developed hydrocephalus and grossly dilated
      lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced alpha
      ketoglutarate. Stem and transit amplifying/progenitor cell populations were
      expanded, and proliferation increased. Cells expressing SVZ markers infiltrated
      surrounding brain regions. SVZ cells also gave rise to proliferative
      subventricular nodules. DNA methylation was globally increased, while
      hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle
      and stem cell genes, and shared an expression signature with human gliomas.
      Idh1R132H mutation in the major adult neurogenic stem cell niche causes a
      phenotype resembling gliomagenesis.

PMID- 27693051
TI  - High-density lipoprotein subclass profile and mortality in patients with coronary
      artery disease: Results from the GENES study.
AB  - BACKGROUND: High-density lipoproteins (HDLs) are highly heterogeneous particles,
      and the specific contribution of each subclass to the prediction of clinical
      outcome in coronary artery disease (CAD) remains controversial. OBJECTIVE: To
      examine the relationship between HDL subclass profile and mortality in patients
      with CAD, using a new and rapid electrophoretic quantitative method for the
      assessment of HDL particle size phenotype. METHODS: We investigated 403 patients
      with CAD admitted for cardiovascular examination in the context of evaluation and
      management of CAD. HDL subclass distribution was analysed using the Quantimetrix
      Lipoprint(r) HDL system. Cumulative survival of patients according to lipid
      variables was determined by the Kaplan-Meier method. The relationship between
      baseline variables and outcome criteria was assessed using Cox proportional
      hazards regression analysis. RESULTS: During follow-up (9.8+/-3.1 years) the
      mortality rate was 31.0%; 60.8% of deaths were related to CAD. The concentration
      of total HDL cholesterol was similar in deceased patients (42+/-13mg/dL) and
      alive patients (43+/-12mg/dL); the concentrations of small, intermediate and
      large HDL cholesterol subclasses were not significantly different in alive and
      deceased patients (P=0.17, P=0.34 and P=0.81, respectively). We did not observe
      any independent associations between overall or cardiovascular mortality and
      total HDL cholesterol or any HDL subclass. However, heart rate, left ventricular
      ejection fraction and severity score for coronary atherosclerosis were more
      associated with mortality than classical cardiovascular risk factors.
      CONCLUSIONS: HDL subclass profile is not associated with mortality in patients
      with CAD. Further investigations linking HDL subclass repartition with prediction
      of residual cardiovascular risk are required.

PMID- 27693052
TI  - Prehospital and in-hospital course of care for patients with acute heart failure:
      Features and impact on prognosis in "real life".
AB  - BACKGROUND: Acute heart failure (AHF) is a life-threatening medical emergency for
      which no new effective therapies have emerged in recent decades. No previous
      study has exhaustively described the entire course of care of AHF patients from
      first medical contact to hospital discharge or assessed its impact on prognosis.
      AIM: To fully describe the course of care and analyze its influence on outcomes
      in patients hospitalized with an AHF syndrome in an academic university center.
      METHODS: One hundred and nineteen adults with AHF from three public academic
      university hospitals were consecutively enrolled in a multicenter prospective
      observational cohort study. All of the emergency departments, intensive care
      units, coronary care units, cardiology wards and other medical wards participated
      in the study. RESULTS: The composite primary outcome (6-month rate of
      cardiovascular death, readmission for acute heart failure, acute coronary
      syndrome or stroke) occurred in 59% of patients. This rate was high and similar
      regardless of first medical contact, type of transport, first medical department
      of admission and number of medical departments involved in the course of care. A
      cardiologist was involved in management in 80% of cases. The global median
      hospital stay was shorter with cardiology vs non-cardiology management (7 days
      [interquartile range 4-11] vs 10 days [interquartile range 7-18]; P=0.003).
      History of hypertension (P=0.004), need for non-invasive ventilation (P=0.023)
      and Lee prognostic score (P=0.028) were independently associated with the primary
      outcome. CONCLUSIONS: Morbimortality and readmissions were high regardless of the
      course of care in patients admitted for AHF in real life. The reduction in
      hospital stay when cardiologists were involved in management encourages the
      creation of "mobile AHF cardiology teams".

PMID- 27693053
TI  - Does Pelvic Sagittal Inclination in the Supine and Standing Positions Change Over
      10 Years of Follow-Up After Total Hip Arthroplasty?
AB  - BACKGROUND: Functional anteversion and inclination of the cup change as the
      pelvic sagittal inclination (PSI) changes. The purposes of this study were to
      investigate the chronological changes of PSI during a 10-year follow-up period
      after total hip arthroplasty (THA) and to report the characteristics of patients
      who showed a greater than 10 degrees  change in the PSI from the supine to the
      standing position. METHODS: The subjects were 70 patients who were followed up
      for 10 years after THA. PSI values in the supine and standing positions were
      measured by 2D-3D matching using computed tomography images and pelvic
      radiographs. PSI values before THA and 1, 5, and 10 years after THA were compared
      in both the supine and standing positions. RESULTS: Supine PSI showed less than 5
      degrees  of change, whereas standing PSI showed a significant decrease with time
      over the 10-year period. Although 43% of patients with less than 10 degrees  of
      difference in the PSI between the supine and standing positions before THA
      increased PSI posteriorly (reclining) more than 10 degrees  in standing from the
      supine position at 10 years, no late dislocation was observed. CONCLUSION: Supine
      PSI showed no significant change, but standing PSI showed a significant increase
      posteriorly with time over a 10-year period. However, this PSI change did not
      reach the level that it caused negative consequences such as late dislocation.
      The pelvic position in the supine position might still be a good functional
      reference position of the pelvis for aiming to achieve proper cup alignment at 10
      years.

PMID- 27693054
TI  - A Randomized Clinical Trial Comparing Posterior Cruciate-Stabilizing vs Posterior
      Cruciate-Retaining Prostheses in Primary Total Knee Arthroplasty: 10-Year Follow
      Up.
AB  - BACKGROUND: This 10-year follow-up compares health-related quality of life (HRQL)
      and reoperations in 100 subjects who were randomized to receive posterior
      cruciate ligament substituting (PS) or posterior cruciate ligament retaining (CR)
      total knee arthroplasty. We previously reported 2-year results. METHODS: Subjects
      were enrolled preoperatively and randomized at surgery. Subjects completed HRQL
      questionnaires at all evaluation points. Subjects were re-evaluated at 2 and 10
      years with reoperations determined through regional medical record review and
      patient report. RESULTS: Over 10 years, 25 (25%) subjects died, 2 subjects were
      revised and withdrew, and 11 (11%) subjects were lost to follow-up. Of survivors,
      62 of 75 (83%) were evaluated at 10 years. Twenty-eight (37%) subjects provided
      HRQL, radiographic, and reoperation status, 28 (37%) subjects completed HRQL
      evaluations and reoperation status only, and 6 (8%) subjects provided
      radiographic and reoperation follow-up. Both groups retained good HRQL between 2
      and 10 years with no group differences noted (P > .35). One revision (CR
      subject), secondary to deep joint infection, occurred within 2 years with 1
      further revision (PS subject) occurring at 3 years postoperatively. One subject
      (PS subject) required manipulation under anesthesia within 3 months of surgery.
      Four subjects required late patellar resurfacing (1 CR subject, 3 PS subjects)
      but were retained in the 10-year evaluation. Overall, reoperations were not
      significantly different between groups (P = .26). CONCLUSION: Over 10 years
      postoperatively, both the PS and CR total knee arthroplasty performed well with
      subjects reporting acceptable levels of HRQL up to 10 years postoperatively; low
      levels of revision or reoperation were reported in both groups.

PMID- 27693055
TI  - [Answer to Dr. Rinaldo Pellicano's letter about the article "Maternal infection
      due to Helicobacter pylori does not increase the risk of the infection in the
      first trimester of the life of their infants"].

PMID- 27693056
TI  - Mechanistic Details of Early Steps in Coenzyme Q Biosynthesis Pathway in Yeast.
AB  - Coenzyme Q (Q) is a redox lipid that is central for the energetic metabolism of
      eukaryotes. The biosynthesis of Q from the aromatic precursor 4-hydroxybenzoic
      acid (4-HB) is understood fairly well. However, biosynthetic details of how 4-HB
      is produced from tyrosine remain elusive. Here, we provide key insights into this
      long-standing biosynthetic problem by uncovering molecular details of the first
      and last reactions of the pathway in the yeast Saccharomyces cerevisiae, namely
      the deamination of tyrosine to 4-hydroxyphenylpyruvate by Aro8 and Aro9, and the
      oxidation of 4-hydroxybenzaldehyde to 4-HB by Hfd1. Inactivation of the HFD1 gene
      in yeast resulted in Q deficiency, which was rescued by the human enzyme ALDH3A1.
      This suggests that a similar pathway operates in animals, including humans, and
      led us to propose that patients with genetically unassigned Q deficiency should
      be screened for mutations in aldehyde dehydrogenase genes, especially ALDH3A1.

PMID- 27693058
TI  - Biomimetic Thioesters as Probes for Enzymatic Assembly Lines: Synthesis,
      Applications, and Challenges.
AB  - Thioesters play essential roles in many biosynthetic pathways to fatty acids,
      esters, polyketides, and non-ribosomal peptides. Coenzyme A (CoA) and related
      phosphopantetheine thioesters are typically employed as activated acyl units for
      diverse C-C, C-O, and C-N coupling reactions. To study and control these
      enzymatic assembly lines in vitro and in vivo structurally simplified analogs
      such as N-acetylcysteamine (NAC) thioesters have been developed. This review
      gives an overview on experimental strategies enabled by synthetic NAC thioesters,
      such as the elucidation of complex biosynthetic pathways and enzyme mechanisms as
      well as precursor-directed biosynthesis and mutasynthesis. The review also
      summarizes synthetic protocols and protection group strategies to access these
      versatile synthetic tools, which are reactive and often unstable compounds. In
      addition, alternative phosphopantetheine thioester mimics are presented that can
      be used as protein tags or suicide inhibitors for protein crosslinking and off
      loading probes to elucidate polyketide intermediates.

PMID- 27693057
TI  - Analysis of the RNA Binding Specificity Landscape of C5 Protein Reveals Structure
      and Sequence Preferences that Direct RNase P Specificity.
AB  - RNA binding proteins (RBPs) are typically involved in non-equilibrium cellular
      processes, and specificity can arise from differences in ground state, transition
      state, or product states of the binding reactions for alternative RNAs. Here, we
      use high-throughput methods to measure and analyze the RNA association kinetics
      and equilibrium binding affinity for all possible sequence combinations in the
      precursor tRNA binding site of C5, the essential protein subunit of Escherichia
      coli RNase P. The results show that the RNA sequence specificity of C5 arises due
      to favorable RNA-protein interactions that stabilize the transition state for
      association and bound enzyme-substrate complex. Specificity is further impacted
      by unfavorable RNA structure involving the C5 binding site in the ground state.
      The results illustrate a comprehensive quantitative approach for analysis of RNA
      binding specificity, and show how both RNA structure and sequence preferences of
      an essential protein subunit direct the specificity of a ribonucleoprotein
      enzyme.

PMID- 27693060
TI  - Conformation Selective Antibody Enables Genome Profiling and Leads to Discovery
      of Parallel G-Quadruplex in Human Telomeres.
AB  - G-quadruplexes are specialized secondary structures in nucleic acids that possess
      significant conformational polymorphisms. The precise G-quadruplex conformations
      in vivo and their relevance to biological functions remain controversial and
      unclear, especially for telomeric G-quadruplexes. Here, we report a novel single
      chain variable fragment (scFv) antibody, D1, with high binding selectivity for
      parallel G-quadruplexes in vitro and in vivo. Genome-wide chromatin
      immunoprecipitation using D1 and deep-sequencing revealed the consensus sequence
      for parallel G-quadruplex formation, which is characterized by G-rich sequence
      with a short loop size (<3 nt). By using D1, telomeric parallel G-quadruplex was
      identified and its formation was regulated by small molecular ligands targeting
      and telomere replication. Together, parallel G-quadruplex specific antibody D1
      was found to be a valuable tool for determination of G-quadruplex and its
      conformation, which will prompt further studies on the structure of G-quadruplex
      and its biological implication in vivo.

PMID- 27693059
TI  - Bidirectional Allosteric Communication between the ATP-Binding Site and the
      Regulatory PIF Pocket in PDK1 Protein Kinase.
AB  - Allostery is a phenomenon observed in many proteins where binding of a
      macromolecular partner or a small-molecule ligand at one location leads to
      specific perturbations at a site not in direct contact with the region where the
      binding occurs. The list of proteins under allosteric regulation includes AGC
      protein kinases. AGC kinases have a conserved allosteric site, the
      phosphoinositide-dependent protein kinase 1 (PDK1)-interacting fragment (PIF)
      pocket, which regulates protein ATP-binding, activity, and interaction with
      substrates. In this study, we identify small molecules that bind to the ATP
      binding site and affect the PIF pocket of AGC kinase family members, PDK1 and
      Aurora kinase. We describe the mechanistic details and show that although PDK1
      and Aurora kinase inhibitors bind to the conserved ATP-binding site, they
      differentially modulate physiological interactions at the PIF-pocket site. Our
      work outlines a strategy for developing bidirectional small-molecule allosteric
      modulators of protein kinases and other signaling proteins.

PMID- 27693061
TI  - Sample preparation procedures utilized in microbial metabolomics: An overview.
AB  - Bacteria are remarkably diverse in terms of their size, structure and biochemical
      properties. Due to this fact, it is hard to develop a universal method for
      handling bacteria cultures during metabolomic analysis. The choice of suitable
      processing methods constitutes a key element in any analysis, because only
      appropriate selection of procedures may provide accurate results, leading to
      reliable conclusions. Because of that, every analytical experiment concerning
      bacteria requires individually and very carefully planned research methodology.
      Although every study varies in terms of sample preparation, there are few general
      steps to follow while planning experiment, like sampling, separation of cells
      from growth medium, stopping their metabolism and extraction. As a result of
      extraction, all intracellular metabolites should be washed out from cell
      environment. What is more, extraction method utilized cannot cause any chemical
      decomposition or degradation of the metabolome. Furthermore, chosen extraction
      method should correlate with analytical technique, so it will not disturb or
      prolong following sample preparation steps. For those reasons, we observe a need
      to summarize sample preparation procedures currently utilized in microbial
      metabolomic studies. In the presented overview, papers concerning analysis of
      extra- and intracellular metabolites, published over the last decade, have been
      discussed. Presented work gives some basic guidelines that might be useful while
      planning experiments in microbial metabolomics.

PMID- 27693062
TI  - Evaluation of particulate matter emissions from manganese alloy production using
      life-cycle assessment.
AB  - Life-cycle assessments (LCAs) provide a wealth of industry data to assist in
      evaluating the environmental impacts of industrial processes and product supply
      chains. In this investigation, data from a recent LCA covering global manganese
      alloy production was used to evaluate sources of particulate matter (PM)
      emissions associated with the manganese alloy supply chain. The analysis is aimed
      at providing an empirical, industry-averaged breakdown of the contribution that
      processes and emissions controls have on total emissions, manganese releases and
      occupational exposure. The assessment shows that 66% of PM emissions associated
      with manganese production occur beyond manganese facilities. Direct or on-site
      emissions represent 34% of total PM and occur predominantly as disperse sources
      during mineral extraction and hauling, and as primary furnace emissions. The
      largest contribution of manganese-bearing PM at ground-level is associated with
      fugitive emissions from metal and slag tapping, casting, crushing and screening.
      The evaluation provides a high-level ranking of emissions by process area, to
      assist in identifying priority areas for industry-wide initiatives to reduce
      emissions and occupational exposure of manganese. The range of PM emission levels
      in industry indicate that further enhancements in PM emissions can be achieved by
      sharing of best practices in emissions controls, limiting furnace conditions
      which lead to by-passing of emissions controls and application of secondary
      emission controls to capture fugitive emissions during tapping and casting. The
      LCA approach to evaluating PM emissions underscores the important role that
      process optimization and resource efficiency have on reducing PM emissions
      throughout the manganese supply chain.

PMID- 27693063
TI  - On the validity and errors of the pseudo-first-order kinetics in ligand-receptor
      binding.
AB  - The simple bimolecular ligand-receptor binding interaction is often linearized by
      assuming pseudo-first-order kinetics when one species is present in excess. Here,
      a phase-plane analysis allows the derivation of a new condition for the validity
      of pseudo-first-order kinetics that is independent of the initial receptor
      concentration. The validity of the derived condition is analyzed from two
      viewpoints. In the first, time courses of the exact and approximate solutions to
      the ligand-receptor rate equations are compared when all rate constants are
      known. The second viewpoint assesses the validity through the error induced when
      the approximate equation is used to estimate kinetic constants from data.
      Although these two interpretations of validity are often assumed to coincide, we
      show that they are distinct, and that large errors are possible in estimated
      kinetic constants, even when the linearized and exact rate equations provide
      nearly identical solutions.

PMID- 27693064
TI  - Colorectal cancer with venous tumor thrombosis.
AB  - Colorectal cancer is seldom accompanied by venous tumor thrombosis, and little is
      known about the features of venous tumor thrombosis in colorectal cancer.
      However, some reports show that colorectal cancer patients can develop venous
      tumor thrombosis and warn clinicians not to overlook this complication. In this
      report, we perform a review of 43 previously reported cases and investigate the
      characteristics of colorectal cancer accompanied by venous tumor thrombosis. The
      histological type of more than half of the cases was moderately differentiated
      adenocarcinoma, which is known to be aggressive. Among 41 cases with available
      data on liver metastasis, eight patients had synchronous liver metastasis, and
      liver metastatic recurrence after surgical resection was indicated in 10
      patients. This liver metastatic rate was high compared to general colorectal
      cancer. However, 11 of 43 patients with venous tumor thrombosis could survive for
      more than 2 years after the diagnosis, although five of the 11 patients had liver
      metastasis. A long survival can be anticipated for patients following complete
      tumor resection and adjuvant chemotherapy. A greater accumulation of cases will
      help elucidate the characteristics of colorectal cancer with venous tumor
      thrombosis and improve the treatment strategy.

PMID- 27693065
TI  - Gastrectomy with limited surgery for elderly patients with gastric cancer.
AB  - BACKGROUND/OBJECTIVE: Elderly patients with gastric cancer can receive standard
      gastrectomy or gastrectomy with reduced nodal dissection, i.e., limited surgery,
      in order to prevent postoperative complications. This study evaluated the
      feasibility of gastrectomy with limited surgery for elderly patients with gastric
      cancer. METHODS: A total of 267 elderly patients (>=70 years old) were divided
      into two groups according to the level of nodal dissection: patients who received
      nodal dissection according to guidelines were included in the standard surgery
      group (standard group), and those who received reduced nodal dissection were
      included in the limited surgery group (limited group). The surgical outcomes of
      the two groups were compared. RESULTS: There were 170 patients in the standard
      group and 97 patients in the limited group. The limited group had significantly
      poorer nutrition status and a significantly higher proportion with comorbidities.
      Morbidity and mortality were similar in both groups. Multivariate analysis showed
      that the overall survival rates were significantly worse in patients with
      advanced age, male gender, low body mass index, low prognostic nutrition index,
      and higher tumor stage. The disease-specific survival rate was significantly
      lower in the limited group than in the standard group (p<0.001). CONCLUSION:
      Gastrectomy according to the gastric treatment guidelines for elderly patients
      with gastric cancer is recommended. Elderly male patients with poor nutrition
      have poor prognosis; prognostic nutrition index <40. Limited surgery is a
      treatment option for such patients.

PMID- 27693066
TI  - Tension Gastrothorax as a Complication of Bochdalek Hernia.

PMID- 27693067
TI  - Esophageal Rupture After Ghost Pepper Ingestion.
AB  - BACKGROUND: The ghost pepper, or "bhut jolokia," is one of the hottest chili
      peppers in the world. Ghost peppers have a measured "heat" of > 1,000,000
      Scoville heat units (SHU), more than twice the strength of a habanero pepper. To
      our knowledge, no significant adverse effects of ghost pepper ingestion have been
      reported. CASE REPORT: A 47-year-old man presented to the Emergency Department
      (ED) with severe abdominal and chest pain subsequent to violent retching and
      vomiting after eating ghost peppers as part of a contest. A subsequent chest x
      ray study showed evidence of a left-sided pleural effusion and patchy
      infiltrates. A computed tomography scan of the abdomen and pelvis showed
      pneumomediastinum with air around the distal esophagus, suggestive of a
      spontaneous esophageal perforation and a left-sided pneumothorax. The patient was
      intubated and taken immediately to the operating room, where he was noted to have
      a 2.5-cm tear in the distal esophagus, with a mediastinal fluid collection
      including food debris, as well as a left-sided pneumothorax. The patient was
      extubated on hospital day 14, and was discharged home with a gastric tube in
      place on hospital day 23. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?:
      Spontaneous esophageal rupture, Boerhaave syndrome, is a rare condition
      encountered by emergency physicians, with a high mortality rate. This case serves
      as an important reminder of a potentially life- threatening surgical emergency
      initially interpreted as discomfort after a large spicy meal.

PMID- 27693068
TI  - A Hanging and Its Complications.
AB  - Hanging has become the second most common form of successful suicide in the
      United States. Along with a high mortality rate, the long-term morbidity is
      consequential for both the individual patient and society. A thorough knowledge
      of the clinical approach will assist the emergency physician in providing optimal
      care and helping to minimize delayed respiratory complications. Using a case
      based scenario, the initial management strategies along with rational evidence
      based treatments are reviewed.

PMID- 27693069
TI  - Superficial Temporal Artery Pseudoaneurysm Presenting as A Suspected Sebaceous
      Cyst.

PMID- 27693070
TI  - Is There a Role for Intravenous Subdissociative-Dose Ketamine Administered as an
      Adjunct to Opioids or as a Single Agent for Acute Pain Management in the
      Emergency Department?
AB  - BACKGROUND: Whether acute or chronic, emergency physicians frequently encounter
      patients reporting pain. It is the responsibility of the emergency physician to
      assess and evaluate, and if appropriate, safely and effectively reduce pain.
      Recently, analgesics other than opioids are being considered in an effort to
      provide safe alternatives for pain management in the emergency department (ED).
      Opioids have significant adverse effects such as respiratory depression,
      hypotension, and sedation, to say nothing of their potential for abuse. Although
      ketamine has long been used in the ED for procedural sedation and rapid sequence
      intubation, it is used infrequently for analgesia. Recent evidence suggests that
      ketamine use in subdissociative doses proves to be effective for pain control and
      serves as a feasible alternative to traditional opioids. This paper evaluates
      ketamine's analgesic effectiveness and safety in the ED. METHODS: This is a
      literature review of randomized controlled trials, systematic reviews, meta
      analyses, and observational studies evaluating ketamine for pain control in the
      ED setting. Based on these search parameters, eight studies were included in the
      final analysis and graded based on the American Academy of Emergency Medicine
      Clinical Practice Committee manuscript review process. RESULTS: A total of eight
      papers were reviewed in detail and graded. Recommendations were given based upon
      this review process. CONCLUSIONS: Subdissociative-dose ketamine (low-dose
      ketamine) is effective and safe to use alone or in combination with opioid
      analgesics for the treatment of acute pain in the ED. Its use is associated with
      higher rates of minor, but well-tolerated adverse side effects.

PMID- 27693071
TI  - Role of Pediatric Emergency Physicians in Identifying Bullying.
AB  - BACKGROUND: Bullying is an important public health issue with broad implications.
      Although this issue has been studied extensively, there is limited emergency
      medicine literature addressing bullying. The emergency department (ED) physician
      has a unique opportunity to identify children and adolescents that are victims of
      bullying, and make a difference in their lives. OBJECTIVE: Our aim is to discuss
      the role of the emergency physician (EP) in identifying patients who have been
      victims of bullying and how to provide effective management as well as referral
      for further resources. DISCUSSION: This document provides a framework for
      recognizing, stabilizing, and managing children who have experienced bullying.
      With the advent of social media, bullying behavior is not limited to in-person
      situations, and often occurs via electronic communication, further complicating
      recognition because it may not impart any physical harm to the child. Recognition
      of bullying requires a high level of suspicion, as patients may not offer this
      history. After the stabilization of any acute or overt indications of physical
      injury, along with obtaining a history of the mechanism of injury, the EP has the
      opportunity to identify the existence of bullying as the cause of the injury, and
      can address the issue in the ED while collaborating with "physician-extenders,"
      such as social workers, toward identifying local resources for further support.
      CONCLUSIONS: The ED is an important arena for the assessment and management of
      children who have experienced bullying. It is imperative that EPs on the front
      lines of patient care address this public health epidemic. They have the
      opportunity to exert a positive impact on the lives of the children and families
      who are the victims of bullying.

PMID- 27693072
TI  - Acute Toxicity from Topical Cocaine for Epistaxis: Treatment with Labetalol.
AB  - BACKGROUND: Topical cocaine is sometimes used for the treatment of epistaxis, as
      it has both potent anesthetic and vasoconstrictive properties. Cocaine has
      unpredictable cardiovascular effects, such as sudden hypertension, tachycardia,
      coronary arterial vasoconstriction, and dysrhythmia. CASE REPORT: We report a
      case of acute iatrogenic cardiovascular toxicity from the use of topical cocaine
      in a 56-year-old man presenting to the Emergency Department with profound
      epistaxis. To prepare for cauterization and nasal packing, the patient received
      4% topical cocaine-soaked nasal pledgets. He became hypertensive, tachypneic,
      tachycardic, and dysphoric immediately after administration. To directly counter
      these adverse hyperadrenergic effects, the patient was given 10 mg intravenous
      labetalol, a mixed beta- and alpha-blocker. This instantly normalized his vital
      signs and adverse subjective effects. His epistaxis was successfully treated, and
      he was discharged 1 h later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?:
      We believe that emergency physicians should be aware of the unpredictable acute
      cardiovascular toxicity of topical cocaine. Labetalol represents an effective
      first-line treatment, which, unlike benzodiazepines, directly counters the
      pharmacologic effects of cocaine and has no respiratory or sedative side effects.
      Labetalol, with its mixed beta/alpha-blocking properties, also mitigates the
      potential for "unopposed alpha-stimulation."

PMID- 27693073
TI  - Jaundice, Anemia, and Hypoxemia.

PMID- 27693074
TI  - Comment on "'Lipid Rescue' for Tricyclic Antidepressant Cardiotoxicity".

PMID- 27693075
TI  - Best Clinical Practice: Current Controversies in Evaluation of Low-Risk Chest
      Pain-Part 1.
AB  - BACKGROUND: Chest pain is a common presentation to the emergency department (ED),
      though the majority of patients are not diagnosed with acute coronary syndrome
      (ACS). Many patients are admitted to the hospital due to fear of ACS. OBJECTIVE:
      Our aim was to investigate controversies in low-risk chest pain evaluation,
      including risk of missed ACS, stress test, and coronary computed tomography
      angiography (CCTA). DISCUSSION: Chest pain accounts for 10 million ED visits in
      the United States annually. Many patients are at low risk for a major cardiac
      adverse event (MACE). With negative troponin and nonischemic electrocardiogram
      (ECG), the risk of MACE and myocardial infarction (MI) is < 1%. The American
      Heart Association recommends further evaluation in low- to intermediate-risk
      patients within 72 h. These modalities add little to further risk stratification.
      These evaluations do not appropriately risk stratify patients who are already at
      low risk, nor do they diagnose acute MI. CCTA is an anatomic evaluation of the
      coronary vasculature with literature support to decrease ED length of stay,
      though it is associated with downstream testing. Literature is controversial
      concerning further risk stratification in already low-risk patients. CONCLUSIONS:
      With nonischemic ECG and negative cardiac biomarker, the risk of ACS approaches <
      1%. Use of stress test and CCTA for risk stratification of low-risk chest pain
      patients is controversial. These tests may allow prognostication but do not
      predict ACS risk beyond ECG and troponin. CCTA may be useful for intermediate
      risk patients, though further studies are required.

PMID- 27693076
TI  - Comparison of Metal and Plastic Disposable Laryngoscope Blade with Reusable
      Macintosh Blade in Difficult and Inhalation Injury Airway Scenario: A Manikin
      Study.
AB  - BACKGROUND: Single-use plastic blades (SUPB) and single-use metal blades (SUMB)
      for direct laryngoscopy and tracheal intubation have not yet been compared with
      reusable metal blades (RUMB) in difficult airway scenarios. OBJECTIVE: The
      purpose of our manikin study was to compare the effectiveness of these different
      laryngoscope blades in a difficult airway scenario, as well as in a difficult
      airway scenario with simulated severe inhalation injury. METHODS: Thirty
      anesthetists performed tracheal intubation (TI) with each of the three
      laryngoscope blades in the two scenario manikins. RESULTS: In the inhalation
      injury scenario, SUPB were associated with prolonged intubation times when
      compared with the metal blades. In the inhalation injury scenario, both metal
      laryngoscope blades provided a quicker, easier, and safer TI. In the difficult
      airway scenario, intubation times were significantly prolonged in the SUPB group
      in comparison to the RUMB group, but there were no significant differences
      between the SUPB and the SUMB. In this scenario, the RUMB demonstrated the
      shortest intubation times and seems to be the most effective device. CONCLUSIONS:
      Generally, results are in line with previous studies showing significant
      disadvantages of SUPB in both manikin scenarios. Therefore, metal blades might be
      beneficial, especially in the airway management of patients with inhalation
      injury.

PMID- 27693077
TI  - Impact of lipid markers and high-sensitivity C-reactive protein on the value of
      the 99th percentile upper reference limit for high-sensitivity cardiac troponin
      I.
AB  - OBJECTIVES: i) To assess the relationship between lipid markers and high
      sensitivity C-reactive protein (hs-CRP), and high-sensitivity cardiac troponin I
      (hs-cTnI) in the reference population, and ii) to evaluate the impact of lipid
      markers and hs-CRP on the 99th percentile upper reference limit (URL) for hs
      cTnI. METHODS: 531 questionnaire-identified presumably healthy individuals were
      enrolled in a single-center, cross-sectional study. Surrogate biomarkers for
      diabetes, myocardial and renal dysfunction were used to refine the healthy cohort
      (n=408). Lipid profile, total cholesterol:high-density lipoprotein cholesterol
      (HDL-C) ratio, non-HDL-C, apolipoprotein AI (apoAI), apolipoprotein B (apoB),
      apoB:apoAI ratio, lipoprotein(a), small dense low-density lipoprotein cholesterol
      (LDL-C) and hs-CRP were determined. RESULTS: Individuals with detectable vs. non
      detectable hs-cTnI concentrations more often showed elevated LDL-C (60% vs. 46%;
      p=0.002), apoB (73% vs. 61%; p=0.008), apoB:apoAI ratio (53% vs. 40%; p=0.005)
      and lipoprotein(a) (15% vs. 7%; p=0.015). The apoB:apoAI ratio and to a lesser
      extent other lipid markers, but not hs-CRP, were positively associated with hs
      cTnI concentration in univariate and multivariate analyses. Exclusion of
      individuals with elevated apoB:apoAI ratio or apoB, but not hs-CRP, lowered the
      99th percentile URL in the healthy cohort respectively by 12.9% (6.2 vs. 5.4ng/L)
      and 14.5% (6.2 vs. 5.3ng/L). The corresponding reduction for both lipid
      biomarkers in the presumably healthy population was 24.0% (7.5 vs. 5.7ng/L).
      CONCLUSION: Our study demonstrates that atherogenic lipid markers, particularly
      apoB:apoAI ratio or apoB, influence the 99th percentile URL for hs-cTnI.

PMID- 27693078
TI  - Effect of HLA mismatching at HLA-A, -B, and -DRB1 for umbilical-cord blood
      transplantation in Taiwan.
AB  - Unrelated cord blood transplantation has become a reliable alternative therapy
      for children and adults owing to that one or two antigen/allele mismatches
      between a patient and the cord blood donor are acceptable without occurrence of
      graft-versus-host disease. To investigate the relationship between the number and
      types of mismatches and relapse, we compared the number of mismatched and non
      mismatched donor-recipient pairs, number of mismatched alleles, and number of
      mismatched antigens at each of the Human Leukocyte Antigen (HLA) -A, -B, and -DR
      loci, respectively. The result indicates that the number of mismatched antigens
      at the HLA-A locus was significantly associated with occurrence of relapse (X2P
      value=0.0243; RR=1.49, 95% CI: 1.04-2.13). Additionally, the number of mismatched
      donor-recipient pairs and the number of mismatched alleles at the HLA-DR locus
      was negatively associated with risks of relapse (X2P-value=0.0028; RR=0.52, 95%
      CI: 0.31-0.89). In this study, we found that the mismatch at the HLA-A locus is
      associated with increased risk of relapse; while the mismatch at the HLA-DR locus
      is innocuous. Hence, we suggest that the well-matched HLA-A alleles were most
      critical for matching HLA alleles between umbilical-cord blood transplantation
      donors and recipients. In other words, cord blood transplantation requires less
      stringent HLA matching, if there are two 5/6 or 4/6 HLA matched donors, it's
      better to choose HLA-A matched donor at least.

PMID- 27693079
TI  - Transcriptional regulation of the uncoupling protein-1 gene.
AB  - Regulated transcription of the uncoupling protein-1 (UCP1) gene, and subsequent
      UCP1 protein synthesis, is a hallmark of the acquisition of the differentiated,
      thermogenically competent status of brown and beige/brite adipocytes, as well as
      of the responsiveness of brown and beige/brite adipocytes to adaptive regulation
      of thermogenic activity. The 5' non-coding region of the UCP1 gene contains
      regulatory elements that confer tissue specificity, differentiation dependence,
      and neuro-hormonal regulation to UCP1 gene transcription. Two main regions-a
      distal enhancer and a proximal promoter region-mediate transcriptional regulation
      through interactions with a plethora of transcription factors, including nuclear
      hormone receptors and cAMP-responsive transcription factors. Co-regulators, such
      as PGC-1alpha, play a pivotal role in the concerted regulation of UCP1 gene
      transcription. Multiple interactions of transcription factors and co-regulators
      at the promoter region of the UCP1 gene result in local chromatin remodeling,
      leading to activation and increased accessibility of RNA polymerase II and
      subsequent gene transcription. Moreover, a commonly occurring A-to-G polymorphism
      in close proximity to the UCP1 gene enhancer influences the extent of UCP1 gene
      transcription. Notably, it has been reported that specific aspects of obesity and
      associated metabolic diseases are associated with human population variability at
      this site. On another front, the unique properties of the UCP1 promoter region
      have been exploited to develop brown adipose tissue-specific gene delivery tools
      for experimental purposes.

PMID- 27693080
TI  - The efficient cell-SELEX strategy, Icell-SELEX, using isogenic cell lines for
      selection and counter-selection to generate RNA aptamers to cell surface
      proteins.
AB  - Aptamers are short single-stranded nucleic acid molecules that are selected in
      vitro from a large random sequence library based on their high and specific
      affinity to a target molecule by a process known as SELEX. Cell-SELEX that
      employs whole living cells overexpressing the defined cell surface proteins (for
      selection) and appropriate mock cells (for counter-selection) has been widely
      used as a valid and feasible method for generating aptamers against specific cell
      surface proteins. However, the endogenous expression of target proteins in mock
      cells or the heterogeneity of surface proteins between selection and counter
      selection cells often impeded the isolation of proper aptamers against target
      proteins. To solve this problem, we developed "Isogenic cell-SELEX" (Icell SELEX
      in short) method, in which isogenic cell lines were manipulated for counter
      selection by microRNA-mediated silencing and for selection by overexpression of
      target proteins. As a model experiment, we targeted integrin alpha V (ITGAV),
      which is a major transmembrane receptor expressed in almost all the cells, and
      established ITGAV-overexpressed and -downregulated HEK293 cells for selection and
      counter-selection, respectively. By taking advantage of a hundred-fold difference
      in the expression level of ITGAV between these two isogenic cell lines, we easily
      isolated several anti-ITGAV aptamers, whose binding to the cell-surface ITGAV was
      confirmed by flow cytometry with the dissociation constant of 300-400 nM range.
      We assume that Icell-SELEX could be applicable to a wide range of cell-surface
      proteins including various transmembrane proteins of biological and
      pharmacological significance.

PMID- 27693081
TI  - H2AK119 monoubiquitination regulates Angiotensin II receptor mediated macrophage
      infiltration and renal fibrosis in type 2 diabetic rats.
AB  - Monocyte chemoattractant protein (MCP-1) and transforming growth factor-beta (TGF
      beta1)-markers of inflammation and fibrosis, are central to type 2 diabetic
      nephropathy (T2DN) progression. The epigenetic basis of their expression has also
      been explored to certain extent. H2A lysine 119 monoubiquitination (H2AK119Ub), a
      repressive chromatin mark regulates progression of hyperglycaemia induced
      fibrosis in glomerular mesangial cells. However, how H2AK119Ub affects the
      expression of MCP-1 and TGF-beta1 and their regulation by Angiotensin II receptor
      subtypes remains unknown. In the current study, we aimed to study the effect of
      Angiotensin II receptors' blockade on the macrophage infiltration and histone
      modifications occurring at the promoter region of Mcp1 and Tgfb1in high fat diet
      fed and low dose streptozotocin treated male Wistar rats. Hereby, we present the
      first report delineating a distinct link between H2AK119Ub and macrophage
      infiltration and fibrosis i.e. the enrichment of H2AUb at Mcp1 and Tgfb1 promoter
      region was found to reduce drastically in the T2DN which could be significantly
      reversed by Telmisartan and was further elevated by PD123319. We could conclude
      that the Angiotensin II mediated macrophage infiltration in T2DN is regulated at
      least partially by H2AK119Ub through both AT1 and AT2 receptors, which to the
      best of our knowledge, presents the first report for the regulation of Mcp1 by
      H2AK119Ub. Thus an approach targeting AT1R blockade and AT2R activation
      accompanied by an epigenetic modulator may be more suitable to ameliorate the
      macrophage infiltration and fibrosis associated with T2DN.

PMID- 27693082
TI  - Culture and nonverbal expressions of empathy in clinical settings: A systematic
      review.
AB  - OBJECTIVE: To conduct a systematic review of studies examining how culture
      mediates nonverbal expressions of empathy with the aim to improve clinician cross
      cultural competency. METHODS: We searched three databases for studies of
      nonverbal expressions of empathy and communication in cross-cultural clinical
      settings, yielding 16,143 articles. We examined peer-reviewed, experimental or
      observational articles. Sixteen studies met inclusion criteria. RESULTS:
      Nonverbal expressions of empathy varied across cultural groups and impacted the
      quality of communication and care. Some nonverbal behaviors appeared universally
      desired and others, culturally specific. Findings revealed the impact of
      nonverbal communication on patient satisfaction, affective tone, information
      exchange, visit length, and expression decoding during cross-cultural clinical
      encounters. Racial discordance, patients' perception of physician racism, and
      physician implicit bias are among factors that appear to influence information
      exchange in clinical encounters. CONCLUSION: Culture-based norms impact
      expectations for specific nonverbal expressions within patient-clinician dyads.
      Nonverbal communication plays a significant role in fostering trusting provider
      patient relationships, and is critical to high quality care. PRACTICE
      IMPLICATIONS: Medical education should include training in interpretation of
      nonverbal behavior to optimize empathic cross-cultural communication and training
      efforts should accommodate norms of local patient populations. These efforts
      should reduce implicit biases in providers and perceived prejudice in patients.

PMID- 27693083
TI  - "Forewarned and forearmed": Long-term childhood cancer survivors' and parents'
      information needs and implications for survivorship models of care.
AB  - OBJECTIVE: This mixed-method study assessed 1) survivors' and parents'
      information needs; and 2) associations between unmet information needs and
      clinical and socio-demographic characteristics. METHODS: Stage 1: CCS and parents
      of CCS, >5years post-diagnosis completed a questionnaire on information needs,
      overall health and perceived risk. Predictors for unmet information needs were
      assessed by multivariable regression. Stage 2: participants were interviewed in
      depth on these topics. RESULTS: Questionnaires were completed by 485 participants
      comprising 322 survivors (mean age: 26.7years, SD=7.9; time since diagnosis:
      19.7years, SD=8.8) and 163 parents (child age: 12.9years, SD=2.4; time since
      diagnosis: 9.7years, SD=2.3), and complemented by 70 interviews. Survivors
      reported unmet information needs about late effects (57.5%) and parents for
      fertility issues (62.5%). Survivors had more unmet needs for medical information
      whereas parents had significantly more regarding sexual issues and lifestyle.
      Being a parent (p=0.001), dissatisfaction with follow-up care (p=0.003), lower
      overall health (p=0.014), higher perceived risk of late effects (p<0.001), and
      greater anxiety/depression (p<0.001) were significantly associated with more
      unmet needs. CONCLUSION: Unmet information needs were common for survivors and
      parents of CCS. PRACTICE IMPLICATIONS: Future efforts towards tailoring
      information on potential late effects, healthy lifestyles and follow-up care may
      help to address unmet information needs.

PMID- 27693084
TI  - Parenting a child with chronic illness as they transition into adulthood: A
      systematic review and thematic synthesis of parents' experiences.
AB  - OBJECTIVE: To understand how parents view and experience their role as their
      child with a long-term physical health condition transitions to adulthood and
      adult healthcare services. METHODS: Five databases were systematically searched
      for qualitative articles examining parents' views and experiences of their
      child's healthcare transition. Papers were quality assessed and thematically
      synthesised. RESULTS: Thirty-two papers from six countries, spanning a 17-year
      period were included. Long-term conditions were diverse. Findings indicated that
      parents view their child's progression toward self-care as an incremental process
      which they seek to facilitate through up-skilling them in self-management
      practices. Parental perceptions of their child's readiness, wellness, competence
      and long-term condition impacted on the child' progression to healthcare
      autonomy. A lack of transitional healthcare and differences between paediatric
      and adult services served as barriers to effective transition. Parents were
      required to adjust their role, responsibilities and behaviour to support their
      child's growing independence. CONCLUSION: Parents can be key facilitators of
      their child's healthcare transition, supporting them to become experts in their
      own condition and care. To do so, they require clarification on their role and
      support from service providers. PRACTICE IMPLICATIONS: Interventions are needed
      which address the transitional care needs of parents as well as young people.

PMID- 27693085
TI  - Winds of Change in Higher Education.
AB  - Recent developments confirm predictions by the IEEE that Massive Open Online
      Courses (MOOCs) will have extensive impact on the future landscape of higher
      education. New degree structures are being introduced and awarding of verified
      MOOC credentials is becoming more widespread, as is recognition of MOOC credits
      by universities and employers. The question is whether this disruptive influence
      is being sufficiently used as an incentive for re-evaluation of standard
      practices and for driving strategic change in higher education.

PMID- 27693086
TI  - Fraud Not a Primary Cause of Irreproducible Results: A Reply to Clark et al.

PMID- 27693087
TI  - Cognitive Phenotypes and the Evolution of Animal Decisions.
AB  - Despite the clear fitness consequences of animal decisions, the science of animal
      decision making in evolutionary biology is underdeveloped compared with decision
      science in human psychology. Specifically, the field lacks a conceptual framework
      that defines and describes the relevant components of a decision, leading to
      imprecise language and concepts. The 'judgment and decision-making' (JDM)
      framework in human psychology is a powerful tool for framing and understanding
      human decisions, and we apply it here to components of animal decisions, which we
      refer to as 'cognitive phenotypes'. We distinguish multiple cognitive phenotypes
      in the context of a JDM framework and highlight empirical approaches to
      characterize them as evolvable traits.

PMID- 27693088
TI  - Immune checkpoint inhibitors for nonsmall cell lung cancer treatment.
AB  - Immune checkpoint inhibition with blocking antibodies that target cytotoxic T
      lymphocyte antigen-4 (CTLA-4) and the programmed cell death protein 1 (PD-1)
      pathway [PD-1/programmed death-ligand 1 (PD-L1)] have demonstrated promise in a
      variety of malignancies. While ipilimumab has been approved as a CTLA-4 blocking
      antibody by the US Food and Drug Administration for the treatment of advanced
      melanoma, it is still not approved for lung cancer treatment. In contrast,
      nivolumab and pembrolizumab, both PD-1 blocking antibodies, have been approved
      for second-line treatment of nonsmall cell lung cancer in 2015 because of their
      high potency and long-lasting effects in some patient subgroups. Other PD-1 and
      PD-L1 monoclonal antibodies are also in active development phase. Treatment with
      such immune checkpoint inhibitors is associated with a unique pattern of immune
      related adverse events or side effects. Combination approaches involving CTLA-4
      and PD-1/PD-L1 blockade or checkpoint inhibitors with chemotherapy or
      radiotherapy are being investigated to determine whether they may enhance the
      efficacy of treatment. Despite many challenges ahead, immunotherapy with
      checkpoint inhibitors has already become a new and important treatment modality
      for lung cancer in the last decade following the discovery of targeted therapy.

PMID- 27693089
TI  - Contribution of magnetic resonance imaging in lung cancer imaging.
AB  - Lung cancer is the leading cause of cancer death worldwide. Prognosis and
      treatment outcomes are known to be related to the disease stage at the time of
      diagnosis. Therefore, an accurate assessment of the extent of disease is critical
      to determine the most appropriate therapy. Currently available imaging modalities
      for diagnosis and follow-up consist of morphological and functional imaging.
      Morphological investigations are mainly performed with CT-scan and in some cases
      with MRI. In this review, we describe the contribution of MRI in lung cancer
      staging focusing on solid pulmonary nodule characterization and TNM staging
      assessment using chest and whole-body MRI examinations, detailing in each chapter
      current recommendations and future developments.

PMID- 27693090
TI  - Evaluation of lung tumor response to therapy: Current and emerging techniques.
AB  - Lung tumor response to therapy may be evaluated in most instances by
      morphological criteria such as RECIST 1.1 on computed tomography (CT) or magnetic
      resonance imaging (MRI). However, those criteria are limited because they are
      based on tumoral dimensional changes and do not take into account other
      morphologic criteria such as density evaluation, functional or metabolic changes
      that may occur following conventional or targeted chemotherapy. New techniques
      such as dual-energy CT, PET-CT, MRI including diffusion-weighted MRI has to be
      considered into the new technical armamentarium for tumor response evaluation.
      Integration of all informations provided by the different imaging modalities has
      to be integrated and represents probably the future goal of tumor response
      evaluation. The aim of the present paper is to review the current and emerging
      imaging criteria used to evaluate the response of therapy in the field of lung
      cancer.

PMID- 27693091
TI  - Outcome of metastatic urothelial carcinoma treated by systemic chemotherapy:
      Prognostic factors based on real-world clinical practice in Japan.
AB  - AIM: To clarify prognostic factors of metatstatic urothelial carcinoma treated by
      systemic chemotherapy in real-world clinical practice in the Japanese population.
      MATERIALS AND METHODS: A total of 228 patients with metastatic urothelial
      carcinoma undergoing systemic chemotherapy between 2000 and 2013 were included in
      the present multi-institutional study. The gemcitabine plus cisplatin regimen was
      administered as first-line chemotherapy to 131 patients, whereas methotrexate,
      vinblastine, doxorubicin, and cisplatin or its modified regimen was given to 71
      patients. Of the 228 patients, 119 received at least 2 different regimens and 22
      underwent resection of metastases (metastasectomy). Multivariate survival
      analysis was performed using the Cox proportional hazards model. The
      characteristics included were age, sex, Eastern Cooperative Oncology Group
      performance status (PS), primary site, pathology of primary site, hemoglobin
      levels, lactate dehydrogenase levels, C-reactive protein levels, corrected
      calcium levels, estimated glomerular filtration rate levels, history of prior
      chemotherapy, metastatic sites, resection of primary site, number of metastatic
      organs, and metastasectomy. RESULTS: The median overall survival (OS) time was 17
      months. On multivariate analysis, female sex, good Eastern Cooperative Oncology
      Group PS at presentation, hemoglobin level>=10g/dl, and single organ metastasis
      were significant independent predictors of prolonged OS. For the survival effect
      of metastasectomy, the median OS time of the 22 patients with metastasectomy was
      53 months, which was significantly longer when compared with patients not
      undergoing metastasectomy (15mo). After adjustment for the 4 aforementioned
      prognostic factors, metastasectomy still remained significant (hazard ratio:
      0.364, P = 0.0008). CONCLUSIONS: Female sex, more favorable PS at presentation,
      hemoglobin level>10g/dl, and single organ metastasis were favorable prognostic
      factors. In addition, metastasectomy was associated with long-term disease
      control.

PMID- 27693093
TI  - Complete genome sequence of Bacillus thuringiensis serovar alesti BGSC 4C1, a
      typical strain with toxicity to Lepidoptera insects.
AB  - Bacillus thuringiensis serovar alesti was used to control caterpillars from
      1970s. Here we reported the complete genome of BGSC 4C1, the type strain of this
      serovar. It has a circular chromosome and six plasmids. The largest plasmid
      pBMB267 contains five insecticidal crystal protein genes (two copies of cry1Ae,
      cry1Gb, cry2Ab, and a novel cry1M-type gene) and three vegetative insecticidal
      protein genes (a novel binary toxin gene operon vip1-vip2 and vip3Aa). Besides,
      the strain also has many genes encodeing virulence factors, and some secondary
      metabolite biosynthetic gene clusters involved in synthesis of antimicrobial
      peptides and bacteriocins. In addition, there is a poly gamma-glutamate synthesis
      gene cluster, whose product is a candidate to control inflammasome-mediated
      disorders and potential in many other fields.

PMID- 27693092
TI  - Combinatorial deletions of glgC and phaCE enhance ethanol production in
      Synechocystis sp. PCC 6803.
AB  - Synechocystis sp. PCC 6803 is an attractive host for bio-ethanol production. In
      the present study, a nitrogen starvation approach was applied on an ethanol
      producing strain for inhibiting the growth, since ethanol production competes
      with the cell growth. The effect of gene deletions in the glycogen and
      polyhydroxybutyrate (PHB) synthesis pathways was investigated. Measurements of
      intracellular glycogen and PHB revealed that the glycogen was accumulated under
      the nitrogen starvation condition and the gene deletion of glycogen synthesis
      pathway caused the accumulation of PHB. The ethanol producing strain harboring
      deletions for both the glycogen and the PHB synthesis pathways
      (DeltaglgCDeltaphaCE/EtOH) produced ethanol at the specific rate of 240mgg (dry
      cell weight)-1 day-1 under the nitrogen starvation condition. In a high cell
      density culture (OD730=50) using this DeltaglgCDeltaphaCE/EtOH strain, the
      ethanol production rates were 1.08 and 2.01gL-1 day-1 under light conditions of
      40 and 80MUmolm-2s-1, respectively.

PMID- 27693094
TI  - Stereoselectivity of formation of monoterpene - Amino acids hybrid molecules in
      the reaction of monoterpene nitroso chlorides with alpha-amino acid derivatives.
AB  - Reaction of nitrosochlorides of natural monoterpene hydrocarbons (+)-3-carene and
      (-)-alpha-pinene with L-amino acids and their methyl esters results in
      stereoselective formation of terpene-amino acids hybrids, which belong to the
      series of alpha-substituted amino oximes. The reaction with an excess of racemic
      DL-amino acids and their derivatives induces partial resolution of the amino acid
      components and formation of the diastereomeric mixtures of the terpene-amino
      acids hybrids, with diastereomeric excess varying from 0 to 100%.

PMID- 27693095
TI  - Clinical practice guidelines for vitamin D in the United Arab Emirates.
AB  - In the UAE and the Gulf region in general, there are several intricate public
      health issues in the context of vitamin D deficiency that needs to be addressed.
      Changes in lifestyle such as diet, lack of exercise, cultural habits, avoiding
      sun exposure due to excessive heat, and other risk factors predispose those who
      live in GULF countries, such as Emiratis likely to becoming vitamin D deficient.
      Consequently, the prevalence of vitamin D deficiency is high, and new guidelines
      are needed to overcome this major public health issue. Peer-reviewed papers
      related to guidelines and those vitamin D-related papers relevant to the Middle
      Eastern region were extracted from multiple research databases using key words
      according to the general guidelines from the Preferred Reporting Items for
      Systematic Analysis. This guideline was prepared focusing on the United Arab
      Emirate and the Gulf populations, to overcome the high incidence of vitamin D
      deficiency and to improve overall health. We recommend the following vitamin D
      supplementations for different groups of people: (A) Breastfed infants supplement
      with 400 IU/day up to age 6 months, and 400-600 IU/day between 6 and 12 months,
      depending on daily intake of total vitamin D and sun exposure; (B) for children
      and adolescents of age 1-18 years supplement with 600-1000 IU/day depending on
      the body weight; (C) adults greater than 18 years', supplementation with 1000
      2000 IU/day is recommended, while, (D) the elderly (over 65 years) should be
      supplemented with 2000 IU/day, throughout the year; (E) pregnant and breast feed
      women, 2000 IU/day from the first trimester of pregnancy. (F) Premature infants,
      supplementation of 400-800 IU/daystart from the first days of life. (G) For
      obese, individuals and those with metabolic syndrome, supplementation of 2000
      IU/day (H) For individuals with dark skin complexions and for night workers,
      supplementation of 1000-2000 IU/day (25-50MUg/day), throughout the year,
      depending on body weight. The goal of supplementation is to achieve and longer
      term maintenance of serum 25(OH)D concentration of 30-50ng/mL.

PMID- 27693096
TI  - Clinical significance of serum carbohydrate antigen 19.9 and duke pancreatic
      monoclonal antigen type 2 for the prediction of hematogenous metastases in
      patients with pancreatic ducal adenocarcinoma.
AB  - OBJECTIVES: The aim of the present study was to investigate the effectiveness of
      serum carbohydrate antigen (CA) 19.9 and duke pancreatic monoclonal antigen type
      2 (DUPAN-2) levels in the prediction of early hematogenous metastases and as
      indicators of neoadjuvant therapy in patients with pancreatic ductal
      adenocarcinoma (PDAC). METHODS: Of the 293 enrolled PDAC patients, 61 had
      hematogenous metastases at the initial evaluation. One hundred and twenty
      patients without metastases underwent surgical resection. Of the 120 patients who
      underwent surgical resection, 45 underwent preoperative treatment and 29
      developed early hematogenous metastases within 1 year after the surgery. In
      patients who underwent preoperative therapy, serum CA 19.9 and DUPAN-2 levels
      were measured within 2 weeks before the preoperative therapy and the subsequent
      surgery. RESULTS: The elevated serum CA 19.9 and DUPAN-2 levels were
      significantly associated with hematogenous metastasis at initial evaluation and
      early hematogenous metastasis after surgery. The rate of early hematogenous
      metastasis and overall survival (OS) in patients with high CA 19.9 and/or high
      DUPAN-2 (CA 19.9 > 200 U/mL and/or DUPAN-2 >300 U/mL) were 46.3% and 18 months,
      respectively, whereas the metastatic rate and OS in patients with low CA 19.9 and
      DUPAN-2 were 12.7% and 37.5 months, respectively. Furthermore, in patients with
      high CA 19.9 and/or high DUPAN-2, preoperative therapy significantly reduced the
      rate of early hematogenous metastasis and prolonged the OS. CONCLUSIONS: Serum CA
      19.9 and DUPAN-2 levels are useful predictors of early hematogenous metastasis
      and indicators for effectiveness of neoadjuvant therapy in PDAC patients.

PMID- 27693097
TI  - Pain assessment in chronic pancreatitis: A comparative review of methods.
AB  - BACKGROUND: Patients with chronic pancreatitis (CP) frequently report chronic
      abdominal pain that adversely impacts their quality of life. Assessment of pain
      in CP is required for clinical management and clinical studies. International
      consensus guidelines recognized a lack of specific and validated pain assessment
      tools for CP. Therefore, the aim of this systematic review is to identify and
      compare all clinical studies that assessed pain in the context of a treatment for
      pain in CP. METHODS: A systematic literature search was performed in PubMed,
      Cochrane Library and Ovid MEDLINE. The search identified all intervention studies
      for pain in CP and the pain assessment tools used based on pre-defined inclusion
      and exclusion criteria. RESULTS: Of 341 articles identified, 137 studies were
      included. Pain assessment tools were both general and CP-specific. The latter
      were used in only 22 (16%) studies. Despite recommendations the aspects of pain
      assessed were limited and variable between tools. Validation of these tools in CP
      patients was limited to quality of life measures. None of the pain assessment
      tools evaluated duration of pain and postprandial pain. CONCLUSIONS: There are no
      published pain assessment tools for CP that includes all relevant aspects of
      pain. There is the need to develop a comprehensive and validated pain assessment
      tool for patients with CP to standardised pain assessment, identify likely
      underlying pain mechanisms, help select appropriate treatments, report outcomes
      from interventions, improve clinical communication and aid the allocation of
      patients to clinical trials.

PMID- 27693098
TI  - Serratus anterior and trapezius muscle activity during knee push-up plus and knee
      plus exercises performed on a stable, an unstable surface and during sling
      suspension.
AB  - OBJECTIVES: Push-up plus variations are commonly prescribed to clients during
      shoulder rehabilitation. The purpose of this study was to compare
      electromyographic (EMG) activities of the serratus anterior (SA), upper (UT), and
      lower trapezius (LT) during a knee push-up plus and knee-plus exercise performed
      on various surfaces. STUDY DESIGN: Within-subjects Repeated-Measure Design.
      PARTICIPANTS: 19 healthy, young female participants performed both exercises on a
      stable and unstable surface and during sling-suspension. OUTCOME MEASURES:
      Surface EMG activities were recorded and average amplitudes were presented as a
      percentage of the maximal voluntary contraction. A two-way repeated-measures
      ANOVA was performed to determine differences in activity for each muscle.
      RESULTS: SA showed no significant differences between exercises and was
      independent of the base of support (p > 0.05). Muscle activity of UT (95% CI
      [1.2, 1.4]) and LT (95% CI [2.4, 3.5]) showed slightly greater values when
      performing the knee push-up plus compared to the knee-plus exercise. CONCLUSIONS:
      The isolated protraction of the shoulder girdle in a kneeling position is as
      sufficient as the push-up plus in activating the SA selectively. Therefore, we
      recommended this exercise for clients who are unable to perform an entire push-up
      or should avoid detrimental stress on the shoulder joint.

PMID- 27693099
TI  - Distinct cut task strategy in Australian football players with a history of groin
      pain.
AB  - OBJECTIVES: This study aimed to explore the differences in the magnitude of
      movement variability and strategies utilized during an unanticipated cut task
      between players with and without a history of groin pain. DESIGN: Cross-sectional
      design. SETTING: Biomechanics laboratory. PARTICIANTS: Male Australian football
      players with (HISTORY; n = 7) or without (CONTROL; n = 10) a history of groin
      pain. OUTCOME MEASURES: Three-dimensional ground reaction forces (GRF) and
      kinematics were recorded during 10 successful trials of an unanticipated cut
      task, and isokinetic hip adduction and abduction strength. Between-group
      differences were determined using independent-samples t-tests and the coefficient
      of variation (CV). RESULTS: Key substantial between-group differences identified
      were that the HISTORY group displayed decreased knee flexion and hip internal
      rotation, increased knee internal rotation and T12-L1 right rotation, and higher
      GRFs during the cut task. They also utilized three invariant systems (ankle, knee
      and T12-L1 joints), while being connected by a segment (hip and L5-S1 joints)
      that displayed increased lumbopelvic movement during the cut task, and decreased
      adductor muscle strength. CONCLUSION: This identifies the need for clinical
      management of the lower limb and thoracic segment to improve functional movement
      patterns in athletes with a history of a groin injury.

PMID- 27693101
TI  - Heart-rate deceleration predicting the determination of costly punishment:
      Implications for its involvement in cognitive effort expended in overriding self
      interest.
AB  - Previous studies have investigated which biological markers predict the decision
      to reject unfair monetary offers, termed costly punishment, in the ultimatum game
      (UG). One study showed that a phasic deceleratory response in heart rate (HR) is
      evoked in the responder more readily by offers that will be rejected than by
      offers that will be accepted. However, owing to the paucity of supporting
      evidence, it remains unclear whether and why HR deceleration can predict the
      decisions of UG responders. In this paper, we report two separate studies (Study
      1 and Study 2) using modified versions of the UG to explore factors modulating HR
      deceleration. In Study 1, as well as unfair offers, fair offers induced greater
      HR deceleration when responders were forced to reject offers compared to when
      they were forced to accept offers. In Study 2, a high rejection rate for very
      unfair offers was sustained, regardless of the size of the offers, but HR
      deceleration was increased for unfair but large offers, relative to unfair, small
      offers. Moreover, HR deceleration was associated with the rejection of large
      offers. However, across the two studies, HR deceleration did not simply vary
      depending on unfairness. These findings support the possibility that HR
      decelerates as a function of cognitive load in determining costly punishment.

PMID- 27693100
TI  - Diagnostic validity of physical examination tests for common knee disorders: An
      overview of systematic reviews and meta-analysis.
AB  - INTRODUCTION: More evidence on diagnostic validity of physical examination tests
      for knee disorders is needed to lower frequently used and costly imaging tests.
      OBJECTIVE: To conduct a systematic review of systematic reviews (SR) and meta
      analyses (MA) evaluating the diagnostic validity of physical examination tests
      for knee disorders. METHODS: A structured literature search was conducted in five
      databases until January 2016. Methodological quality was assessed using the
      AMSTAR. RESULTS: Seventeen reviews were included with mean AMSTAR score of 5.5 +/
      2.3. Based on six SR, only the Lachman test for ACL injuries is diagnostically
      valid when individually performed (Likelihood ratio (LR+):10.2, LR-:0.2). Based
      on two SR, the Ottawa Knee Rule is a valid screening tool for knee fractures (LR
      :0.05). Based on one SR, the EULAR criteria had a post-test probability of 99%
      for the diagnosis of knee osteoarthritis. Based on two SR, a complete physical
      examination performed by a trained health provider was found to be diagnostically
      valid for ACL, PCL and meniscal injuries as well as for cartilage lesions.
      CONCLUSION: When individually performed, common physical tests are rarely able to
      rule in or rule out a specific knee disorder, except the Lachman for ACL
      injuries. There is low-quality evidence concerning the validity of combining
      history elements and physical tests.

PMID- 27693102
TI  - Reconstructing ERP amplitude effects after compensating for trial-to-trial
      latency jitter: A solution based on a novel application of residue iteration
      decomposition.
AB  - Stimulus-locked averaged event-related potentials (ERPs) are among the most
      frequently used signals in Cognitive Neuroscience. However, the late, cognitive
      or endogenous ERP components are often variable in latency from trial to trial in
      a component-specific way, compromising the stability assumption underlying the
      averaging scheme. Here we show that trial-to-trial latency variability of ERP
      components not only blurs the average ERP waveforms, but may also attenuate
      existing or artificially induce condition effects in amplitude. Hitherto this
      problem has not been well investigated. To tackle this problem, a method to
      measure and compensate component-specific trial-to-trial latency variability is
      required. Here we first systematically analyze the problem of single trial
      latency variability for condition effects based on simulation. Then, we introduce
      a solution by applying residue iteration decomposition (RIDE) to experimental
      data. RIDE separates different clusters of ERP components according to their time
      locking to stimulus onsets, response times, or neither, based on an algorithm of
      iterative subtraction. We suggest to reconstruct ERPs by re-aligning the
      component clusters to their most probable single trial latencies. We demonstrate
      that RIDE-reconstructed ERPs may recover amplitude effects that are diminished or
      exaggerated in conventional averages by trial-to-trial latency jitter. Hence,
      RIDE-corrected ERPs may be a valuable tool in conditions where ERP effects may be
      compromised by latency variability.

PMID- 27693105
TI  - Clinical Islet Xenotransplantation: A Step Forward.

PMID- 27693103
TI  - Bone Graft Prefabrication Following the In Vivo Bioreactor Principle.
AB  - Large bone defect treatment represents a great challenge due to the difficulty of
      functional and esthetic reconstruction. Tissue-engineered bone grafts created by
      in vitro manipulation of bioscaffolds, seed cells, and growth factors have been
      considered potential treatments for bone defect reconstruction. However, a
      significant gap remains between experimental successes and clinical translation.
      An emerging strategy for bridging this gap is using the in vivo bioreactor
      principle and flap prefabrication techniques. This principle focuses on using the
      body as a bioreactor to cultivate the traditional triad (bioscaffolds, seed
      cells, and growth factors) and leveraging the body's self-regenerative capacity
      to regenerate new tissue. Additionally, flap prefabrication techniques allow the
      regenerated bone grafts to be transferred as prefabricated bone flaps for bone
      defect reconstruction. Such a strategy has been used successfully for
      reconstructing critical-sized bone defects in animal models and humans. Here, we
      highlight this concept and provide some perspective on how to translate current
      knowledge into clinical practice.

PMID- 27693104
TI  - Characterization of a 2016 Clinical Isolate of Zika Virus in Non-human Primates.
AB  - Animal models are critical to understand disease and to develop countermeasures
      for the ongoing epidemics of Zika virus (ZIKV). Here we report a non-human
      primate model using a 2016 contemporary clinical isolate of ZIKV. Upon
      subcutaneous inoculation, rhesus macaques developed fever and viremia, with
      robust excretion of ZIKV RNA in urine, saliva, and lacrimal fluid. Necropsy of
      two infected animals revealed that systematic infections involving central
      nervous system and visceral organs were established at the acute phrase. ZIKV
      initially targeted the intestinal tracts, spleen, and parotid glands, and
      retained in spleen and lymph nodes till 10days post infection. ZIKV-specific
      immune responses were readily induced in all inoculated animals. The non-human
      primate model described here provides a valuable platform to study ZIKV
      pathogenesis and to evaluate vaccine and therapeutics.

PMID- 27693106
TI  - Thrombotic Thrombocytopenic Purpura with Concomitant Progressive Cerebral
      Microbleeds.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a disease caused by excessive
      platelet thrombi and multisystem vasculopathy. We report a young patient with
      refractory TTP who has developed multiple multifocal cerebral microbleeds on his
      brain magnetic resonance imaging scans. TTP-associated thrombotic microangiopathy
      resulting in diffuse microthrombi formation in the microcirculation and
      hypoperfusion might be an underlying etiology.

PMID- 27693107
TI  - e-NIHSS: an Expanded National Institutes of Health Stroke Scale Weighted for
      Anterior and Posterior Circulation Strokes.
AB  - BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) is the most
      widespread clinical scale used in patients presenting with acute stroke. The
      merits of the NIHSS include simplicity, quickness, and agreement between
      clinicians. The clinical evaluation on posterior circulation stroke remains still
      a limit of NIHSS. METHODS: We assessed the application of a new version of NIHSS,
      the e-NIHSS (expanded NIHSS), adding specific elements in existing items to
      explore signs/symptoms of a posterior circulation stroke. A total of 22
      consecutive patients with suspected vertebrobasilar stroke were compared with 25
      patients with anterior circulation stroke using NIHSS and e-NIHSS. RESULTS: We
      compared the NIHSS and e-NIHSS scores obtained by the 2 examiners, in patients
      with posterior circulation infarct (POCI), using the Wilcoxon test. Patients with
      POCI evaluated with e-NIHSS had an average of 2 points higher than patients
      evaluated with classical NIHSS. The difference was statistically significant (P <
      .05), weighted by the new expanded items. CONCLUSIONS: The NIHSS is a practical
      scale model, with high reproducibility between trained, different examiners,
      focused on posterior circulation strokes, with the same total score and number of
      items of the existing NIHSS. The e-NHISS could improve the sensitivity of NIHSS
      in posterior circulation stroke and could have an impact on clinical trials, as
      well as on outcomes. Further studies are needed to investigate a larger number of
      patients and the correlation between the e-NIHSS score and neuroimaging findings.

PMID- 27693108
TI  - A Comparison of Reinforcement Based Treatment (RBT) versus RBT plus Recovery
      Housing (RBTRH).
AB  - OBJECTIVES: Reinforcement-based treatment (RBT) plus recovery housing (RBTRH)
      improves outcomes for individuals with opioid use disorders. No studies have
      examined the efficacy of RBT in the absence of abstinent-contingent housing.
      METHODS: We compared highly similar participants from a study of outpatient RBT
      (RBT, n=55) and the RBTRH (n=80) arm of a randomized trial wherein participants
      received abstinent-contingent payment for recovery housing sponsored by the
      research program. Abstinence and employment outcomes were assessed at one, three,
      and six months. Regression was used to identify predictors of abstinence.
      Sensitivity analyses explored the impact of housing on outcomes. RESULTS: RBT and
      RBTRH participants had similar abstinence and employment outcomes. Predictors of
      abstinence in the sample included recovery housing residence and employment.
      However, a distinct RBT sub-group emerged, as 33% of the sample accessed self-pay
      RH (RBTSPRH). Sensitivity analyses compared the two RH groups (self-pay and
      program-supported) to RBT outpatient treatment (RBT). The RBTSPRH and RBTRH
      groups had similar abstinence outcomes, and both groups had superior abstinence
      outcomes compared to RBT. The RBTSPRH group had the most sustained effects
      relative to RBT, including higher abstinence rates, and more favorable employment
      outcomes at six months (ps<.05). The RBTSPRH group reported more days of
      employment compared to both the RBT and RBTRH groups at three months (ps<.05).
      CONCLUSIONS: Findings highlight the importance of recovery housing for promoting
      improved outcomes among RBT participants. Research is needed to explore the
      aspects of recovery housing versus outpatient treatment that are associated with
      improved outcomes in the population.

PMID- 27693109
TI  - Lower cerebral blood flow is associated with impairment in multiple cognitive
      domains in Alzheimer's disease.
AB  - INTRODUCTION: We examined the association between decreased cerebral blood flow
      (CBF) and cognitive impairment in Alzheimer's disease (AD), mild cognitive
      impairment (MCI), and subjective cognitive decline (SCD). METHODS: We included
      161 AD, 95 MCI, and 143 SCD patients from the Amsterdam Dementia Cohort. We used
      3-T pseudo-continuous arterial spin labeling to estimate whole-brain and regional
      partial volume-corrected CBF. Neuropsychological tests covered global cognition
      and five cognitive domains. Associations were investigated using linear
      regression analyses. RESULTS: In the whole sample, reduced overall and regional
      CBF was associated with impairment in all cognitive domains. We found significant
      interactions between diagnosis and CBF for language and between diagnosis and
      parietal CBF for global cognition and executive functioning. Stratification
      showed that decreased CBF was associated with worse performance in AD patients
      but not in MCI or SCD. DISCUSSION: Our results suggest that CBF may have
      potential as a functional marker of disease severity.

PMID- 27693110
TI  - Percutaneous balloon mitral valvuloplasty and closure of the left atrial
      appendage: Synergy of two procedures in one percutaneous intervention.
AB  - Mitral stenosis (MS) is frequently associated with the development of atrial
      fibrillation (AF) as a consequence of hemodynamic and inflammatory changes in the
      left atrium. Both conditions predispose to thrombus formation, with frequent
      involvement of the left atrial appendage (LAA), and consequent increase in the
      incidence of systemic thromboembolic events. Percutaneous mitral valvuloplasty
      (PMV) reduces the risk of thromboembolism in patients with significant mitral
      stenosis. Percutaneous LAA closure is also associated with a reduction in
      thromboembolic risk in patients with AF, but there are no data regarding the use
      of this technique in patients with significant mitral valve disease. We report
      the case of a 57-year-old-woman with significant MS and permanent AF, in New York
      Heart Association functional class II, who despite adequate oral anticoagulation
      with acenocoumarol, presented several clinical episodes of systemic
      thromboembolism in the last four years. It was decided to perform a combined
      percutaneous procedure, including both PMV and percutaneous LAA closure with the
      Amplatzer Cardiac Plug device. No significant acute complications occurred and
      the patient was discharged on indefinite treatment with acenocoumarol associated
      with aspirin 100 mg/d for three months. After a one-year follow-up, there have
      been no new embolic episodes or other complications.

PMID- 27693111
TI  - Abnormal electrocardiographic findings in athletes: Correlation with intensity of
      sport and level of competition.
AB  - INTRODUCTION: Athletes can exhibit abnormal electrocardiogram (ECG) phenotypes
      that require further evaluation prior to competition. These are apparently more
      prevalent in high-intensity endurance sports. The purpose of this study was to
      assess the association between ECG findings in athletes and intensity of sport
      and level of competition. METHODS: A cohort of 3423 competitive athletes had
      their ECGs assessed according to the Seattle criteria (SC). The presence of
      abnormal ECGs was correlated with: (1) intensity of sport (low/moderate vs. at
      least one high static or dynamic component); (2) competitive level (regional vs.
      national/international); (3) training volume (<=20 vs. >20 hours/week); (4) type
      of sport (high dynamic vs. high static component). The same endpoints were
      studied according to the 'Refined Criteria' (RC). RESULTS: Abnormal ECGs
      according to the SC were present in 225 (6.6%) athletes, more frequently in those
      involved in high-intensity sports (8.0% vs. 5.4%; p=0.002), particularly in
      dynamic sports, and competing at national/international level (7.1% vs. 4.9%;
      p=0.028). Training volume was not significantly associated with abnormal ECGs. By
      multivariate analysis, high-intensity sport (OR 1.55, 1.18-2.03; p=0.002) and
      national/international level (OR 1.50, 95% CI 1.04-2.14; p=0.027) were
      independent predictors of abnormal ECGs, and these variables, when combined,
      doubled the prevalence of this finding. According to the RC, abnormal ECGs
      decreased to 103 (3.0%), but were also more frequent in high-intensity sports
      (4.2% vs. 2.0%; p<0.001). CONCLUSIONS: There is a positive correlation between
      higher intensity of sports and increased prevalence of ECG abnormalities. This
      relationship persists with the use of more restrictive criteria for ECG
      interpretation, although the number of abnormal ECGs is lower.

PMID- 27693112
TI  - Radiofrequency ablation and predictors for faster recovery for tachycardia
      induced cardiomyopathy in the pediatric population.

PMID- 27693113
TI  - Reply to the letter "Radiofrequency ablation and predictors for faster recovery
      for tachycardia-induced cardiomyopathy in the pediatric population".

PMID- 27693114
TI  - TonB-dependent ligand trapping in the BtuB transporter.
AB  - TonB-dependent transporters are beta-barrel outer membrane proteins occluded by a
      plug domain. Upon ligand binding, these transporters extend a periplasmic motif
      termed the TonB box. The TonB box permits the recruitment of the inner membrane
      protein complex TonB-ExbB-ExbD, which drives import of ligands in the cell
      periplasm. It is unknown precisely how the plug domain is moved aside during
      transport nor have the intermediate states between TonB recruitment and plug
      domain movement been characterized biochemically. Here we employ nanodiscs,
      native gel electrophoresis, and scintillation proximity assays to determine the
      binding kinetics of vitamin B12 to BtuB. The results show that ligand-bound BtuB
      recruits a monomer of TonB (TonB?1-31), which in turn increases retention of
      vitamin B12 within the transporter. The TonB box and the extracellular residue
      valine 90 that forms part of the vitamin B12 binding site are essential for this
      event. These results identify a novel step in the TonB-dependent transport
      process. They show that TonB binding to BtuB trap the ligand, possibly until the
      ExbB-ExbD complex is activated or recruited to ensure subsequent transport.

PMID- 27693115
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases necroinflammation and
      hepatic stellate cell activation but does not exacerbate experimental liver
      fibrosis in mice.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental
      contaminant and high-affinity ligand for the aryl hydrocarbon receptor (AhR).
      Increasing evidence indicates that AhR signaling contributes to wound healing,
      which involves the coordinated deposition and remodeling of the extracellular
      matrix. In the liver, wound healing is attributed to the activation of hepatic
      stellate cells (HSCs), which mediate fibrogenesis through the production of
      soluble mediators and collagen type I. We recently reported that TCDD treatment
      increases the activation of human HSCs in vitro. The goal of this study was to
      determine how TCDD impacts HSC activation in vivo using a mouse model of
      experimental liver fibrosis. To elicit fibrosis, C57BL6/male mice were treated
      twice weekly for 8weeks with 0.5ml/kg carbon tetrachloride (CCl4). TCDD
      (20MUg/kg) or peanut oil (vehicle) was administered once a week during the last
      2weeks. Results indicate that TCDD increased liver-body-weight ratios, serum
      alanine aminotransferase activity, and hepatic necroinflammation in CCl4-treated
      mice. Likewise, TCDD treatment increased mRNA expression of HSC activation and
      fibrogenesis genes, namely alpha-smooth muscle actin, desmin, delta-like homolog
      1, TGF-beta1, and collagen type I. However, TCDD treatment did not exacerbate
      fibrosis, nor did it increase the collagen content of the liver. Instead, TCDD
      increased hepatic collagenase activity and increased expression of matrix
      metalloproteinase (MMP)-13 and the matrix regulatory proteins, TIMP-1 and PAI-1.
      These results support the conclusion that TCDD increases CCl4-induced liver
      damage and exacerbates HSC activation, yet collagen deposition and the
      development of fibrosis may be limited by TCDD-mediated changes in extracellular
      matrix remodeling.

PMID- 27693116
TI  - Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and
      Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast
      Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast
      Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5.
AB  - BACKGROUND: The purpose of this study was to determine the cardiac safety and
      clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin
      with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast
      cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). PATIENTS AND METHODS:
      Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m2)
      followed by 4 cycles of docetaxel (100 mg/m2). Targeted therapy with standard
      dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year.
      Coprimary end points were (1) rate of cardiac events (CEs) in all patients
      defined as clinical congestive heart failure with a significant decrease in left
      ventricular ejection fraction or cardiac deaths; and (2) pathologic complete
      response (pCR) in breast and nodes in the neoadjuvant cohort. An independent
      cardiac review panel determined whether criteria for a CE were met. RESULTS: A
      total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy
      and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2
      months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence
      interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients
      was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall
      survival (OS) for all patients was 79.9% and 90.8%, respectively. CONCLUSION: The
      regimen met predefined criteria for activity of interest with an acceptable rate
      of CEs. Although the pCR percentage was comparable with chemotherapy regimens
      with trastuzumab alone the high RFS and OS are of interest in these high-risk
      populations.

PMID- 27693117
TI  - Distinct and overlapping DNMT1 interactions with multiple transcription factors
      in erythroid cells: Evidence for co-repressor functions.
AB  - DNMT1 is the maintenance DNA methyltransferase shown to be essential for
      embryonic development and cellular growth and differentiation in many somatic
      tissues in mammals. Increasing evidence has also suggested a role for DNMT1 in
      repressing gene expression through interactions with specific transcription
      factors. Previously, we identified DNMT1 as an interacting partner of the TR2/TR4
      nuclear receptor heterodimer in erythroid cells, implicated in the developmental
      silencing of fetal beta-type globin genes in the adult stage of human
      erythropoiesis. Here, we extended this work by using a biotinylation tagging
      approach to characterize DNMT1 protein complexes in mouse erythroleukemic cells.
      We identified novel DNMT1 interactions with several hematopoietic transcription
      factors with essential roles in erythroid differentiation, including GATA1, GFI
      1b and FOG-1. We provide evidence for DNMT1 forming distinct protein subcomplexes
      with specific transcription factors and propose the existence of a "core" DNMT1
      complex with the transcription factors ZBP-89 and ZNF143, which is also present
      in non-hematopoietic cells. Furthermore, we identified the short (17a.a.) PCNA
      Binding Domain (PBD) located near the N-terminus of DNMT1 as being necessary for
      mediating interactions with the transcription factors described herein. Lastly,
      we provide evidence for DNMT1 serving as a co-repressor of ZBP-89 and GATA1
      acting through upstream regulatory elements of the PU.1 and GATA1 gene loci.

PMID- 27693119
TI  - Early onset fetal growth restriction.
AB  - Fetal growth restriction remains a challenging entity with significant variations
      in clinical practice around the world. The different etiopathogenesis of early
      and late fetal growth restriction with their distinct progression of fetal
      severity and outcomes, compounded by doctors and patient anxiety adds to the
      quandary involving its management. This review summarises the literature around
      diagnosing and monitoring early onset fetal growth restriction (early onset FGR)
      with special emphasis on optimal timing of delivery as guided by recent research
      advances.

PMID- 27693121
TI  - Olfactory signaling components and olfactory receptors are expressed in tubule
      cells of the human kidney.
AB  - Cells of the renal tubule system are in direct contact with compounds dissolved
      in the urine, such as short chain fatty acids (SCFA). Murine OR78, a member of
      the olfactory receptor (OR) family, is involved in SCFA-related regulation of
      renal blood pressure in mice. It is still unclear whether OR signaling has an
      impact on human renal physiology. In our study, we showed that OR51E1 and OR11H7,
      both of which can be activated by the SCFA isovaleric acid, are expressed in the
      HK-2 human proximal tubule cell line. We observed a transient increase in
      intracellular Ca2+ when isovaleric acid and 4-methylvaleric acid were added to HK
      2 cells. The isovaleric acid-induced response was dependent on extracellular Ca2+
      and adenylyl cyclase (AC) activation. Furthermore, we demonstrated that the
      canonical olfactory signaling components Galphaolf and ACIII are co-localized
      with OR51E1. The number of cells responding to isovaleric acid correlated with
      the presence of primary cilia on HK-2 cells. OR51E1 protein expression was
      confirmed in the tubule system of human kidney tissue. Our study is the first to
      show the expression of ORs and olfactory signaling components in human kidney
      cells. Additionally, we discuss ORs as potential modulators of the renal
      physiology.

PMID- 27693118
TI  - Passive exposure to agricultural pesticides and risk of childhood leukemia in an
      Italian community.
AB  - BACKGROUND: Exposure to pesticides has been suggested as a risk factor for
      childhood leukemia, but definitive evidence on this relation and the specific
      pesticides involved is still not clear. OBJECTIVE: We carried out a population
      based case-control study in a Northern Italy community to assess the possible
      relation between passive exposure to agricultural pesticides and risk of acute
      childhood leukemia. METHODS: We assessed passive pesticide exposure of 111
      childhood leukemia cases and 444 matched controls by determining density and type
      of agricultural land use within a 100-m radius buffer around children's homes. We
      focused on four common crop types, arable, orchard, vineyard and vegetable,
      characterized by the use of specific pesticides that are potentially involved in
      childhood induced leukemia. The use of these pesticides was validated within the
      present study. We computed the odds ratios (OR) of the disease and their 95%
      confidence intervals (CI) according to type and density of crops around the
      children's homes, also taking into account traffic pollution and high-voltage
      power line magnetic field exposure. RESULTS: Childhood leukemia risk did not
      increase in relation with any of the crop types with the exception of arable
      crops, characterized by the use of 2.4-D, MCPA, glyphosate, dicamba, triazine and
      cypermethrin. The very few children (n=11) residing close to arable crops had an
      OR for childhood leukemia of 2.04 (95% CI 0.50-8.35), and such excess risk was
      further enhanced among children aged <5 years. CONCLUSIONS: Despite the null
      association with most crop types and the statistical imprecision of the
      estimates, the increased leukemia risk among children residing close to arable
      crops indicates the need to further investigate the involvement in disease
      etiology of passive exposure to herbicides and pyrethroids, though such exposure
      is unlikely to play a role in the vast majority of cases.

PMID- 27693122
TI  - Competing Values Framework: A useful tool to define the predominant culture in a
      maternity setting in Australia.
AB  - OBJECTIVE: To identify the predominant culture of an organisation which could
      then assess readiness for change. DESIGN: An exploratory design using the
      Competing Values Framework (CVF) as a self-administered survey tool. SETTING: The
      Maternity Unit in one Australian metropolitan tertiary referral hospital.
      SUBJECTS: All 120 clinicians (100 midwives and 20 obstetricians) employed in the
      maternity service were invited to participate; 26% responded. MAIN OUTCOME
      MEASURE: The identification of the predominant culture of an organisation to
      assess readiness for change prior to the implementation of a new policy. RESULTS:
      The predominant culture of this maternity unit, as described by those who
      responded to the survey, was one of hierarchy with a focus on rules and
      regulations and less focus on innovation, flexibility and teamwork. These results
      suggest that this unit did not have readiness to change. CONCLUSION: There is
      value in undertaking preparatory work to gain a better understanding of the
      characteristics of an organisation prior to designing and implementing change.
      This understanding can influence additional preliminary work that may be required
      to increase the readiness for change and therefore increase the opportunity for
      successful change. The CVF is a useful tool to identify the predominant culture
      and characteristics of an organisation that could influence the success of
      change.

PMID- 27693124
TI  - Inhibitory effect of recombinant human endostatin on the proliferation of
      hypertrophic scar fibroblasts in a rabbit ear model.
AB  - Hypertrophic scar (HS) is a pathological scar that particularly occurs after
      traumatic injuries, surgical procedures and burning. Abnormal activation of
      hypertrophic scar fibroblasts (HSFs) intensifies fibrosis during wound healing.
      Our previous studies demonstrated that recombinant human endostatin
      (rhEndostatin) prevented synovial thickening in adjuvant arthritis (AA) rats via
      inhibition of proliferation and enhancement of apoptosis in synovial fibroblasts.
      However, the effect of this protein on HSF proliferation is not known. This study
      investigated the inhibitory effect of rhEndostatin on the proliferation of
      cultured HSFs in a rabbit ear model. MTT assay and flow cytometric detection were
      performed to investigate HSF proliferation and cell cycle progression,
      respectively. The expression levels of p53, p21, cyclinD1, cyclin-dependent
      kinase 4 (CDK4) and proliferating cell nuclear antigen (PCNA) in HSFs were
      detected using real-time PCR and Western blotting. Our data revealed that HSFs
      treated with rhEndostatin were significantly inhibited in a concentration
      dependent manner with an IC50 value of 100mg/L. Also, rhEndostatin (100mg/L)
      primarily induced G0/G1 and partially G2/M cell cycle arrest of HSFs. There were
      significant decreases in the expression levels of p53, p27, CDK4, cyclinD1 and
      PCNA in HSFs treated with rhEndostatin. In conclusion, rhEndostatin inhibited HSF
      proliferation via G0/G1 and/or G2/M phase arrest of the cell cycle, which was
      partially due to the down-regulation of cyclinD1, CDK4 and PCNA. These findings
      suggest that rhEndostatin may reduce scar hypertrophy in vivo via inhibition of
      HSF proliferation and may be a novel agent for HS treatment.

PMID- 27693123
TI  - The impact of perioperative beta blocker use on patient outcomes after primary
      cytoreductive surgery in high-grade epithelial ovarian carcinoma.
AB  - OBJECTIVE: To quantify the impact of perioperative beta blocker use on survival
      after primary cytoreductive surgery for epithelial ovarian cancer. METHODS: We
      conducted a multi-center retrospective study of all women who underwent primary
      cytoreductive surgery for ovarian cancer (2000-2010). One institution had
      routinely used perioperative beta blockers for patients "at risk" for coronary
      events. The other institution did not routinely use perioperative beta blockers.
      Demographic, operative, and follow up data were collected. Cox proportional
      hazards models were used to assess the effect of beta blockers on progression
      free interval (PFI) as well as overall survival (OS). RESULTS: Out of 185
      eligible patients, 70 received beta blockers and 115 underwent cytoreductive
      surgery without perioperative beta blockers. Both groups were similar in
      demographics. A history of hypertension was present more often in the beta
      blocker group compared to the group that did not receive beta blockers (22% and
      6%, p=0.002). PFI in beta blocker group was greater at 18.2 vs. 15.8months
      (p=0.66). The OS in the beta blocker group was significantly higher at 44.2 vs.
      39.3months (p=0.01). In multivariate analysis, perioperative beta blocker use was
      associated with significant improvement in OS (HR 0.68 (0.46-0.99); p=0.046).
      CONCLUSION: Our study showed an association between perioperative beta blocker
      use and longer overall survival in patients undergoing primary ovarian cancer
      cytoreductive surgery. A prospective randomized clinical trial in this population
      would further validate these results.

PMID- 27693125
TI  - Pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta as
      regulators of angiogenesis and cancer.
AB  - Pleiotrophin (PTN) is a secreted heparin-binding growth factor that through its
      receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta) has a significant
      regulatory effect on angiogenesis and cancer. PTN and RPTPbeta/zeta are over
      expressed in several types of human cancers and regulate important cancer cell
      functions in vitro and cancer growth in vivo. This review begins with a brief
      introduction of PTN and the regulation of its expression. PTN receptors are
      described with special emphasis on RPTPbeta/zeta, which also interacts with
      and/or affects the function of other important targets for cancer therapy, such
      as vascular endothelial growth factor A, alphanubeta3 and cell surface nucleolin.
      PTN biological activities related to angiogenesis and cancer are extensively
      discussed. Finally, up to date approaches of targeting PTN or RPTPbeta/zeta for
      cancer treatment are presented. Insights into the regulatory role of
      PTN/RPTPbeta/zeta on angiogenesis will be extremely beneficial for future
      development of alternative anti-angiogenic approaches in cancer therapy.

PMID- 27693127
TI  - Corrigendum to "Attenuation of transcriptional and signaling responses limits
      viability of rho0Saccharomyces cerevisiae during periods of glucose deprivation"
      [Biochim. Biophys. Acta 1860 (2016) 2563-2575].

PMID- 27693126
TI  - RhoA regulates Activin B-induced stress fiber formation and migration of bone
      marrow-derived mesenchymal stromal cell through distinct signaling.
AB  - BACKGROUND: In our previous study, Activin B induced actin stress fiber formation
      and cell migration in Bone marrow-derived mesenchymal stem cells (BMSCs) in
      vitro. However, the underlying molecular mechanisms are not well studied. RhoA is
      recognized to play a critical role in the regulation of actomyosin cytoskeletal
      organization and cell migration. METHODS: Pull-down assay was performed to
      investigate the activity of RhoA. The dominant-negative mutants of RhoA
      (RhoA(N19)) was used to determine whether RhoA has a role in Activin B-induced
      cytoskeleton organization and cell migration in BMSCs. Cytoskeleton organization
      was examined by fluorescence Rhodamine-phalloidin staining, and cell migration by
      transwell and cell scratching assay. Western blot was carried out to investigate
      downstream signaling cascade of RhoA. Inhibitor and siRNAs were used to detect
      the role of downstream signaling in stress fiber formation and/or cell migration.
      RESULTS: RhoA was activated by Activin B in BMSCs. RhoA(N19) blocked Activin B
      induced stress fiber formation and cell migration. ROCK inhibitor blocked Activin
      B-induced stress fiber formation but enhanced BMSCs migration. Activin B induced
      phosphorylation of LIMK2 and Cofilin, which was abolished by ROCK inhibition.
      Both of siRNA LIMK2 and siRNA Cofilin inhibited Activin B-induced stress fiber
      formation. CONCLUSIONS: RhoA regulates Activin B-induced stress fiber formation
      and migration of BMSCs. A RhoA-ROCK-LIMK2-Cofilin signaling node exists and
      regulates actin stress fiber formation. RhoA regulates Activin B-induced cell
      migration independent of ROCK. GENERAL SIGNIFICANCE: Better understanding of the
      molecular mechanisms of BMSCs migration will help optimize therapeutic strategy
      to target BMSCs at injured tissues.

PMID- 27693128
TI  - Adolescent Awareness and Use of Electronic Cigarettes: A Review of Emerging
      Trends and Findings.
AB  - Adult electronic cigarette (e-cigarette) use is increasing globally, and early
      studies have suggested that similar trends may be observed among the adolescent
      population, albeit at lower levels. The current literature review presents data
      collected since 2014 from 21 cross-sectional studies and one cohort study that
      were all published in English. In particular, it focuses on awareness, ever use,
      past 30-day use, and regular use of e-cigarettes. The article suggests that
      adolescents are nearing complete awareness of e-cigarettes. Furthermore, in
      relation to ever use and past 30-day use, higher prevalence rates continue to be
      reported across time, especially in the United States. Nonetheless, reported
      regular use of e-cigarettes remains much lower than past 30-day use, although
      conclusions are limited due to inconsistencies with measurement and consequent
      lack of cross-cultural applicability. The majority of studies do not report
      whether adolescents use non-nicotine e-cigarettes. There is a current absence of
      longitudinal studies that explore any association between e-cigarettes and
      tobacco use and little qualitative data that may illuminate how and why
      adolescents use e-cigarettes. Through addressing these methodological
      limitations, future research will be able to inform health care and policy more
      effectively.

PMID- 27693129
TI  - Data Mining of Web-Based Documents on Social Networking Sites That Included
      Suicide-Related Words Among Korean Adolescents.
AB  - PURPOSE: To investigate online search activity of suicide-related words in South
      Korean adolescents through data mining of social media Web sites as the suicide
      rate in South Korea is one of the highest in the world. METHODS: Out of more than
      2.35 billion posts for 2 years from January 1, 2011 to December 31, 2012 on 163
      social media Web sites in South Korea, 99,693 suicide-related documents were
      retrieved by Crawler and analyzed using text mining and opinion mining. These
      data were further combined with monthly employment rate, monthly rental prices
      index, monthly youth suicide rate, and monthly number of reported bully victims
      to fit multilevel models as well as structural equation models. RESULTS: The link
      from grade pressure to suicide risk showed the largest standardized path
      coefficient (beta = .357, p < .001) in structural models and a significant random
      effect (p < .01) in multilevel models. Depression was a partial mediator between
      suicide risk and grade pressure, low body image, victims of bullying, and
      concerns about disease. The largest total effect was observed in the grade
      pressure to depression to suicide risk. The multilevel models indicate about 27%
      of the variance in the daily suicide-related word search activity is explained by
      month-to-month variations. A lower employment rate, a higher rental prices index,
      and more bullying were associated with an increased suicide-related word search
      activity. CONCLUSIONS: Academic pressure appears to be the biggest contributor to
      Korean adolescents' suicide risk. Real-time suicide-related word search activity
      monitoring and response system needs to be developed.

PMID- 27693130
TI  - Comparison of Positive Youth Development for Youth With Chronic Conditions With
      Healthy Peers.
AB  - PURPOSE: Adolescents with childhood-onset chronic condition (COCC) are at
      increased risk for physical and psychological problems. Despite being at greater
      risk and having to deal with traumatic experiences and uncertainty, most
      adolescents with COCC do well across many domains. The Positive Youth Development
      (PYD) perspective provides a framework for examining thriving in youth and has
      been useful in understanding positive outcomes for general populations of youth
      as well as at-risk youth. This study aimed to compare levels of PYD assets
      between youth with COCC and youth without illness. METHODS: Participants with
      COCC were recruited from specialty pediatric clinics while healthy participants
      were recruited from a large pediatric primary care practice. Inclusion criteria
      for participants included being (1) English speaking, (2) no documented
      intellectual disability in electronic medical record, and (3) aged between 13 and
      18 years during the recruitment period. Univariate and bivariate analyses on key
      variables were conducted for adolescents with and without COCC. Finally, we
      performed multivariable linear regressions for PYD and its subdomains. RESULTS:
      There were no significant differences between overall PYD or any of the
      subdomains between the two groups. Multivariable linear regression models showed
      no statistically significant relationship between chronic condition status and
      PYD or the subdomains. CONCLUSIONS: The findings from this study support the
      application of the PYD perspective to this population of youth. The results of
      this study suggest that approaches shown to benefit healthy youth, could be used
      to promote positive outcomes for youth with COCC.

PMID- 27693132
TI  - Enabling the Next 25 Years of Cell Biology.

PMID- 27693131
TI  - Timed Up and Go test, atrophy of medial temporal areas and cognitive functions in
      community-dwelling older adults with normal cognition and mild cognitive
      impairment.
AB  - AIM: This study aimed to ascertain if performance on the Timed Up and Go (TUG)
      test is associated with indicators of brain volume and cognitive functions among
      community-dwelling older adults with normal cognition or mild cognitive
      impairment. METHODS: Participants were 80 community-dwelling older adults aged 65
      89years (44 men, 36 women), including 20 with mild cognitive impairment.
      Participants completed the TUG and a battery of cognitive assessments, including
      the Mini-Mental State Examination (MMSE), the Logical Memory I and II (LM-I, LM
      II) subtests of the Wechsler Memory Scale-Revised; and the Trail Making Test A
      and B (TMT-A, TMT-B). Bilateral, right- and left-side medial temporal area
      atrophy as well as whole gray and white matter indices were determined with the
      Voxel-based Specific Regional Analysis System for Alzheimer's Disease. We divided
      participants into three groups based on TUG performance: "better" (<=6.9s);
      "normal" (7-10s); and "poor" (>=10.1s). RESULTS: Worse TMT-A and TMT-B
      performance showed significant independent associations with worse TUG
      performance (P<0.05, P<0.01 for trend, respectively). After adjusting for
      covariates, severe atrophy of bilateral, right-, and left-side medial temporal
      areas were significantly independently associated with worse TUG performance
      (P<0.05 for trend). However, no significant associations were found between MMSE,
      LM-I, LM-II, whole gray and white matter indices, and TUG performance.
      CONCLUSIONS: Worse TUG performance is related to poor performance on TMT-A and
      TMT-B, and is independently associated with severe medial temporal area atrophy
      in community-dwelling older adults.

PMID- 27693133
TI  - Changes in the Updated 2016: WHO Classification of the Myelodysplastic Syndromes
      and Related Myeloid Neoplasms.
AB  - In comparison with the 2008 World Health Organization "Blue Book" on
      hematopoietic neoplasms, a small number of changes have been made in the
      classification. In the lower-risk patients, Refractory Cytopenias with
      Multilineage Dysplasia and Ring Sideroblasts (RCMD-RS) has been separated from
      RCMD to recognize the importance of the SF3B1 mutation. Often there has been
      confusion as to the degree of morphologic dysplasia and/or cytopenias to define
      some of the lower-risk subtypes. In addition, the type of dysplasia or cytopenias
      is not always concordant. Therefore, it seems prudent to apply the more general
      term "myelodysplastic syndrome (MDS)" with single- or multiple-lineage dysplasia.
      Refractory neutropenia or thrombocytopenia has been deemphasized because most
      patients have multilineage dysplasia. In the higher-risk patients, the terms
      Refractory Anemia with Excess Blasts (RAEB) 1 or 2 have been simplified to
      Myelodysplastic Syndrome-Excess Blasts (MDS-EB) 1 or 2 to emphasize the
      importance of the percentage of blasts that dictate therapy. Patients with
      Chronic Myelomonocytic Leukemia (CMML) can be classified into 3 groups: CMML 0,
      1, or 2, based on the percentage of blasts (< 5%, 5%-9%, 10%-19%). Cases with 50%
      or more erythroid precursors will not have the percentage of blasts based on the
      nonerythroid precursors. Previous cases of acute erythroid leukemia
      (myeloid:erythroid type) can be included in the acute myeloid leukemia (AML)
      subtype: AML with MDS-related features.

PMID- 27693134
TI  - Interim PET Scans in Diffuse Large B-Cell Lymphoma: Is It Ready for Prime Time?
AB  - Prognostication of patients with diffuse large B-cell lymphoma (DLBCL) has
      improved in the past decade with a variety of clinical, morphologic, molecular,
      and radiographic methods. Comparable to data on the value of interim positron
      emission tomography (I-PET) in Hodgkin lymphoma, several retrospective and
      prospective studies are attempting to assess the value of I-PET scanning in DLBCL
      patients. In this review, we briefly describe and analyze the various prognostic
      methods in DLBCL with specific focus on the value of I-PET scanning in this
      disease. This is a timely analysis, as tailoring therapies based on prognosis at
      diagnosis are becoming of increased investigational interest.

PMID- 27693135
TI  - The Mesoderm-Forming Gene brachyury Regulates Ectoderm-Endoderm Demarcation in
      the Coral Acropora digitifera.
AB  - Blastoporal expression of the T-box transcription factor gene brachyury is
      conserved in most metazoans [1, 2]. Its role in mesoderm formation has been
      intensively studied in vertebrates [3-6]. However, its fundamental function near
      the blastopore is poorly understood in other phyla. Cnidarians are basal
      metazoans that are important for understanding evolution of metazoan body plans
      [7, 8]. Because they lack mesoderm, they have been used to investigate the
      evolutionary origins of mesoderm [1, 9-11]. Here, we focus on corals, a primitive
      clade of cnidarians that diverged from sea anemones ~500 mya [12]. We developed a
      microinjection method for coral eggs to examine Brachyury functions during
      embryogenesis of the scleractinian coral, Acropora digitifera. Because Acropora
      embryos undergo pharynx formation after the blastopore closes completely [13-15],
      they are useful to understand Brachyury functions in gastrulation movement and
      pharynx formation. We show that blastoporal expression of brachyury is directly
      activated by Wnt/beta-catenin signaling in the ectoderm of coral embryos,
      indicating that the regulatory axis from Wnt/beta-catenin signaling to brachyury
      is highly conserved among eumetazoans. Loss-of-function analysis demonstrated
      that Brachyury is required for pharynx formation but not for gastrulation
      movement. Genome-wide transcriptome analysis demonstrated that genes positively
      regulated by Brachyury are expressed in the ectoderm of Acropora gastrulae, while
      negatively regulated genes are in endoderm. Therefore, germ layer demarcation
      around the blastopore appears to be the evolutionarily conserved role of
      Brachyury during gastrulation. Compared with Brachyury functions in vertebrate
      mesoderm-ectoderm and mesoderm-endoderm demarcation [4-6], our results suggest
      that the vertebrate-type mesoderm may have originated from brachyury-expressing
      ectoderm adjacent to endoderm.

PMID- 27693136
TI  - Centrosome Amplification Increases Single-Cell Branching in Post-mitotic Cells.
AB  - Centrosome amplification is a hallmark of cancer, although we are still far from
      understanding how this process affects tumorigenesis [1, 2]. Besides the
      contribution of supernumerary centrosomes to mitotic defects, their biological
      effects in the post-mitotic cell are not well known. Here, we exploit the effects
      of centrosome amplification in post-mitotic cells during single-cell branching.
      We show that Drosophila tracheal cells with extra centrosomes branch more than
      wild-type cells. We found that mutations in Rca1 and CycA affect subcellular
      branching, causing tracheal tip cells to form more than one subcellular lumen. We
      show that Rca1 and CycA post-mitotic cells have supernumerary centrosomes and
      that other mutant conditions that increase centrosome number also show excess of
      subcellular lumen branching. Furthermore, we show that de novo lumen formation is
      impaired in mutant embryos with fewer centrioles. The data presented here define
      a requirement for the centrosome as a microtubule-organizing center (MTOC) for
      the initiation of subcellular lumen formation. We propose that centrosomes are
      necessary to drive subcellular lumen formation. In addition, centrosome
      amplification increases single-cell branching, a process parallel to capillary
      sprouting in blood vessels [3]. These results shed new light on how centrosomes
      can contribute to pathology independently of mitotic defects.

PMID- 27693137
TI  - Rats Remember Items in Context Using Episodic Memory.
AB  - Vivid episodic memories in people have been characterized as the replay of unique
      events in sequential order [1-3]. Animal models of episodic memory have
      successfully documented episodic memory of a single event (e.g., [4-8]). However,
      a fundamental feature of episodic memory in people is that it involves multiple
      events, and notably, episodic memory impairments in human diseases are not
      limited to a single event. Critically, it is not known whether animals remember
      many unique events using episodic memory. Here, we show that rats remember many
      unique events and the contexts in which the events occurred using episodic
      memory. We used an olfactory memory assessment in which new (but not old) odors
      were rewarded using 32 items. Rats were presented with 16 odors in one context
      and the same odors in a second context. To attain high accuracy, the rats needed
      to remember item in context because each odor was rewarded as a new item in each
      context. The demands on item-in-context memory were varied by assessing memory
      with 2, 3, 5, or 15 unpredictable transitions between contexts, and item-in
      context memory survived a 45 min retention interval challenge. When the memory of
      item in context was put in conflict with non-episodic familiarity cues, rats
      relied on item in context using episodic memory. Our findings suggest that rats
      remember multiple unique events and the contexts in which these events occurred
      using episodic memory and support the view that rats may be used to model
      fundamental aspects of human cognition.

PMID- 27693138
TI  - Honeybees Learn Landscape Features during Exploratory Orientation Flights.
AB  - Exploration is an elementary and fundamental form of learning about the structure
      of the world [1-3]. Little is known about what exactly is learned when an animal
      seeks to become familiar with the environment. Navigating animals explore the
      environment for safe return to an important place (e.g., a nest site) and to
      travel between places [4]. Flying central-place foragers like honeybees (Apis
      mellifera) extend their exploration into distances from which the features of the
      nest cannot be directly perceived [5-10]. Bees perform short-range and long-range
      orientations flights. Short-range flights are performed in the immediate
      surroundings of the hive and occur more frequently under unfavorable weather
      conditions, whereas long-range flights lead the bees into different sectors of
      the surrounding environment [11]. Applying harmonic radar technology for flight
      tracking, we address the question of whether bees learn landscape features during
      their first short-range or long-range orientation flight. The homing flights of
      single bees were compared after they were displaced to areas explored or not
      explored during the orientation flight. Bees learn the landscape features during
      the first orientation flight since they returned faster and along straighter
      flights from explored areas as compared to unexplored areas. We excluded a range
      of possible factors that might have guided bees back to the hive based on
      egocentric navigation strategies (path integration, beacon orientation, and
      pattern matching of the skyline). We conclude that bees localize themselves
      according to learned ground structures and their spatial relations to the hive.

PMID- 27693139
TI  - Imbalanced Activity in the Orbitofrontal Cortex and Nucleus Accumbens Impairs
      Behavioral Inhibition.
AB  - Contemporary models of behavioral regulation maintain that balanced activity
      between cognitive control areas (prefrontal cortex, PFC) and subcortical reward
      related regions (nucleus accumbens, NAC) mediates the selection of appropriate
      behavioral responses, whereas imbalanced activity (PFC < NAC) results in
      maladaptive behavior [1-6]. Imbalance can arise from reduced engagement of PFC
      (via fatigue or stress [7]) or from excessive activity in NAC [8]. Additionally,
      a concept far less researched is that an imbalance can result from simultaneously
      low PFC activity and high NAC activity. This occurs during adolescence, when the
      maturation of PFC lags behind that of NAC and NAC is more functionally active
      compared to adulthood or pre-adolescence [2, 5, 9, 10]. Accordingly, activity is
      disproportionately higher in NAC than in PFC, which may contribute to impulsivity
      and risk-taking exhibited by adolescents [5, 6, 10-12]. Despite having
      explanatory value, support for this notion has been solely correlational. Here,
      we causally tested this using chemogenetics to simultaneously decrease neural
      activity in the orbitofrontal cortex (OFC) and increase activity in NAC in adult
      rats, mimicking the imbalance during adolescence. We tested the effects on
      negative occasion setting, an important yet understudied form of inhibitory
      learning that may be particularly relevant during adolescence. Rats with combined
      manipulation of OFC and NAC were impaired in learning to use environmental cues
      to withhold a response, an effect that was greater than that of either
      manipulation alone. These findings provide direct evidence that simultaneous
      underactivity in OFC and overactivity in NAC can negatively impact behavioral
      control and provide insight into the neural systems that underlie inhibitory
      learning.

PMID- 27693140
TI  - Earliest Onychophoran in Amber Reveals Gondwanan Migration Patterns.
AB  - The anomalous occurrence of supposedly Gondwanan taxa in Laurasian-derived
      regions remains an intriguing chapter of paleobiogeographical history.
      Representatives of Peripatidae, a major subgroup of velvet worms (Onychophora),
      show a disjointed distribution in the neotropics, tropical Africa, and Southeast
      Asia, the latter being the only landmass previously associated with Laurasia [1,
      2]. The arrival of these animals in Southeast Asia is explained by two
      alternative, albeit not mutually exclusive, hypotheses: an early migration via
      Europe before continental drift (Eurogondwana hypothesis) or transportation via
      insular India during the Cretaceous and Paleogene ("out-of-India" hypothesis) [3
      6]. The latter hypothesis is based on a single extant species of Peripatidae,
      Typhloperipatus williamsoni, in India. ?Cretoperipatus burmiticus from Myanmar is
      the oldest fossil onychophoran found in amber [7], dating to sometime between the
      two proposed scenarios, and hence crucial for clarifying how Gondwanan lineages
      of these low-vagility animals reached Southeast Asia (see also Supplemental
      Information). Based on the anatomical reconstruction of ?C. burmiticus using
      synchrotron radiation-based X-ray microtomography (SRMUCT) and comparisons with
      extant taxa, we resolved this fossil species within Onychophora, particularly
      within Peripatidae, with T. williamsoni as its closest extant relative. This
      suggests that an early Eurogondwanan migration of peripatids was the most likely
      event, as Burmese amber is too old to be compatible with the out-of-India
      hypothesis. Moreover, peripatids probably colonized India only recently from
      Myanmar, refuting the putative Gondwanan relict status of Indian onychophorans.
      Finally, preservation artifacts identified in the novel amber material might have
      a major impact on studies of onychophoran stem and/or crown groups.

PMID- 27693141
TI  - Extreme Modification of the Tetrapod Forelimb in a Triassic Diapsid Reptile.
AB  - The tetrapod forelimb is one of the most versatile structures in vertebrate
      evolution, having been co-opted for an enormous array of functions. However, the
      structural relationships between the bones of the forelimb have remained largely
      unchanged throughout the 375 million year history of Tetrapoda, with a radius and
      ulna made up of elongate, paralleling shafts contacting a series of shorter
      carpal bones. These features are consistent across nearly all known tetrapods,
      suggesting that the morphospace encompassed by these taxa is limited by some sort
      of constraint(s). Here, we report on a series of three-dimensionally preserved
      fossils of the small-bodied (<1 m) Late Triassic diapsid reptile Drepanosaurus,
      from the Chinle Formation of New Mexico, USA, which dramatically diverge from
      this pattern. Along with the crushed type specimen from Italy, these specimens
      have a flattened, crescent-shaped ulna with a long axis perpendicular to that of
      the radius and hyperelongate, shaft-like carpal bones contacting the ulna that
      are proximodistally longer than the radius. The second digit supports a massive,
      hooked claw. This condition has similarities to living "hook-and-pull" digging
      mammals and demonstrates that specialized, modern ecological roles had developed
      during the Triassic Period, over 200 million years ago. The forelimb bones in
      Drepanosaurus represent previously unknown morphologies for a tetrapod and, thus,
      a dramatic expansion of known tetrapod forelimb morphospace.

PMID- 27693142
TI  - Sleep-Stage-Specific Regulation of Cortical Excitation and Inhibition.
AB  - Sleep is characterized by unique patterns of cortical activity alternating
      between the stages of slow-wave sleep (SWS) and rapid-eye movement (REM) sleep.
      How these patterns relate to the balanced activity of excitatory pyramidal cells
      and inhibitory interneurons in cortical circuits is unknown. We investigated
      cortical network activity during wakefulness, SWS, and REM sleep globally and
      locally using in vivo calcium imaging in mice. Wide-field imaging revealed a
      reduction in pyramidal cell activity during SWS compared with wakefulness and,
      unexpectedly, a further profound reduction in activity during REM sleep. Two
      photon imaging on local circuits showed that this suppression of activity during
      REM sleep was accompanied by activation of parvalbumin (PV)+ interneurons, but
      not of somatostatin (SOM)+ interneurons. PV+ interneurons most active during
      wakefulness were also most active during REM sleep. Our results reveal a sleep
      stage-specific regulation of the cortical excitation/inhibition balance, with PV+
      interneurons conveying maximum inhibition during REM sleep, which might help
      shape memories in these networks.

PMID- 27693143
TI  - Fate of antibiotics from hospital and domestic sources in a sewage network.
AB  - Investigation of domestic and hospital effluents in a sewage system of an
      elementary watershed showed that antibiotics belonging to eight classes were
      present with concentrations ranging from <LOQ to 50MUgL-1. The compounds most
      often detected in the effluents were the fluoroquinolones (79-100%), the
      sulfonamides (86-100%) and the macrolides (79-86%). Vancomycin, strictly reserved
      for hospital use in France, was detected exclusively in the hospital effluent,
      supporting its pertinent use as a marker of hospital discharge. Beta-lactams,
      which are among the most frequently consumed compounds, were rarely detected in
      the effluents, due to their rapid hydrolysis. Out of 23 antibiotics used in
      veterinary and human medicine, fourteen were quantified in both the wastewater
      treatment plant (WWTP) input and output: erythromycin, amoxicillin, tetracycline,
      trimethoprim, ormethoprim, sulfamethoxazole, vancomycin and seven quinolones
      (flumequine, enrofloxacin, enoxacin, ofloxacin, lomefloxacin, norfloxacin and
      ciprofloxacin). Antibiotic concentrations in the hospital effluent (from 0.04 to
      17.9MUgL-1) were ten times higher than those measured in the domestic effluent
      (from 0.03 to 1.75MUgL-1), contributing to 90% of the antibiotic inputs to the
      WWTP. Some molecules such as sulfamethoxazole, erythromycin and trimethoprim
      displayed higher concentrations after wastewater treatment due to deconjugation
      of their metabolites, which restores the parent molecules. For other compounds,
      the antibiotic elimination showed discrepancies depending on their
      physicochemical properties. For fluoroquinolones, the apparent removal processes
      were mainly based on adsorption mechanisms, followed by settling, leading to
      sludge contamination (from 13 to 18,800MUgkg-1 dry weight).

PMID- 27693144
TI  - Evaluation of index-overlay methods for groundwater vulnerability and risk
      assessment in Kathmandu Valley, Nepal.
AB  - This study aimed at evaluating three index-overlay methods of vulnerability
      assessment (i.e., DRASTIC, GOD, and SI) for estimating risk to pollution of
      shallow groundwater aquifer in the Kathmandu Valley, Nepal. The Groundwater Risk
      Assessment Model (GRAM) model was used to compute the risk to groundwater
      pollution. Results showed that DRASTIC and SI methods are comparable for
      vulnerability assessment as both methods delineate around 80% of the groundwater
      basin area under high vulnerable zone. From the perspective of risk to pollution
      results, DRASTIC and GOD methods are comparable. Nevertheless, all the three
      methods estimate that at least 60% of the groundwater basin is under moderate
      risk to NO3-N pollution, which goes up to 75% if DRASTIC or GOD-based
      vulnerabilities are considered as exposure pathways. Finally, based on strength
      and significance of correlation between the estimated risk and observed NO3-N
      concentrations, it was found that SI method is a better-suited one to assess the
      vulnerability and risk to groundwater pollution in the study area. Findings from
      this study are useful to design strategies and actions aimed to prevent nitrate
      pollution in groundwater of Kathmandu Valley in Nepal.

PMID- 27693145
TI  - Estimating ground-level PM2.5 concentrations in Beijing, China using aerosol
      optical depth and parameters of the temperature inversion layer.
AB  - The aerosol optical depth (AOD) is widely used to predict surface PM2.5
      (particles with an aerodynamic diameter smaller than 2.5MUm) concentrations using
      regression methods, as a way to supplement observations from sparse ground PM2.5
      monitoring networks. Several meteorological parameters, such as surface humidity,
      temperature and height of planetary boundary layer (HPBL), are usually combined
      with AOD to improve the accuracy of the regression model in predicting PM2.5
      concentrations. In this paper, we investigate the role of the temperature
      inversion layer in the prediction of PM2.5 concentrations by the optimal subset
      regression method. The result indicates that the optimal subset regression model
      with the parameters of the depth and temperature difference of the inversion can
      significantly improve the accuracy of the predictions of surface PM2.5
      concentrations, compared with the original regression model with one factor of
      AOD. The determination coefficient (R2) increases from 0.51 to 0.63, and the Root
      Mean Square Error (RMSE) decreases from 40.38 to 35.45MUg/m3. The optimal subset
      regressions were also built for each season. The temperature difference of the
      inversion is introduced into the autumn and winter optimal subset regression, and
      the depth of the inversion is introduced into the spring optimal subset
      regression. The contribution of the inversion parameters to the regression model
      is affected by the different type of the temperature inversion layer present in
      each season.

PMID- 27693146
TI  - Seasonal predictability of water resources in a Mediterranean freshwater
      reservoir and assessment of its utility for end-users.
AB  - In this study we explore the seasonal predictability of water resources in a
      Mediterranean environment (the Boadella reservoir, in north-eastern Spain). Its
      utility for end-users is assessed through the analysis of economic value curve
      areas (EVA). Firstly, we have built monthly multiple linear regression (MLR)
      models for the in-flow, out-flow and volume anomalies by identifying the
      underlying relationships between these predictands and their potential
      predictors, both meteorological and human influenced: rainfall, maximum and
      minimum temperatures, reservoir volume and discharge. Subsequently, we have
      forecast the monthly anomalies with these models for the period 1981-2010 (up to
      seven months ahead). We have tested the aforementioned models with four
      strategies in a leave-one-out cross-validation procedure (LOOCV): a) Climatology
      (Clim.), b) persistence (Pers.), c) antecedent observations+climatology
      (A+Clim.), d) antecedent observations+European Centre for Medium-range Weather
      Forecasts (ECMWF) System 4 anomalies (A+S4). Climatology is the operational
      strategy against which the other approximations are compared. The second and
      third approaches only use observations as input data. Finally, the last one
      combines both observations and ECMWF System 4 forecasts. The LOOCV revealed that
      reservoir volume is the variable best described by the MLR models, followed by in
      flow and out-flow anomalies. In the case of volume anomalies, the predictability
      displayed provides added value with respect to climatology with a minimum of four
      months in advance. For in-flow and out-flow this is true at one month ahead, and
      regarding the latter variable we encounter enhanced predictability also at longer
      horizons for the summer months, when water demands peak (a valuable result for
      end-users). Hence, there is a window of opportunity to develop future operational
      frameworks that could outperform the use of climatology for these variables and
      forecast horizons.

PMID- 27693147
TI  - Microplastics pollution in inland freshwaters of China: A case study in urban
      surface waters of Wuhan, China.
AB  - Microplastics have been considered as an emerging pollutant in the aquatic
      environment. However, research about microplastic pollution in inland freshwaters
      of China is insufficient. The present study investigated the levels of
      microplastics in surface water of 20 urban lakes and urban reaches of the
      Hanjiang River and Yangtze River of Wuhan, the largest city in central China.
      Microplastic concentrations ranged from 1660.0+/-639.1 to 8925+/-1591n/m3 for the
      studied waters, with the highest concentration found in Bei Lake. Microplastic
      abundance in lakes varied markedly in space, and negatively correlated with the
      distance from the city center (p<0.001), which confirmed the important role of
      anthropogenic factors in microplastic distribution. Urban reaches of the Hanjiang
      River and Yangtze River were found to have relatively lower levels of
      microplastics than most of the studied lakes. The major type of microplastics
      among the studied waters was colored plastic, with fiber being the most frequent
      shape. More than 80% of microplastics in number had a size of <2mm. Polyethylene
      terephthalate and polypropylene were the dominant polymer-types of microplastics
      analyzed. This study provided important reference for better understanding
      microplastic levels in inland freshwaters.

PMID- 27693148
TI  - Polycyclic aromatic hydrocarbons in primary school environments: Levels and
      potential risks.
AB  - Although polycyclic aromatic hydrocarbons (PAHs) are priority air pollutants that
      strongly affect human health, information concerning the indoor exposures is
      still limited. This study characterized PAH levels in primary schools and
      evaluated risk for the respective students (aged 8-10years) in comparison with
      school personnel. During January-April 2014, eighteen particulate-bound (PM2.5)
      PAHs (16 USEPA priority compounds, dibenzo[a,l]pyrene, benzo[j]fluoranthene) were
      collected (indoors and outdoors) at ten primary urban schools in Portugal. Total
      mean concentrations (SigmaPAHs) ranged 2.8-54ngm-3 in indoor air, whereas
      corresponding outdoor levels were 7.1-48ngm-3. Indoor/outdoor ratios of lighter
      congeners (2-3 aromatic rings) demonstrated a contribution from indoor origin
      while heavier PAHs (4-6 aromatic rings) originated mostly from infiltration of
      ambient air indoors; traffic (both from diesel and gasoline fuelled vehicles) was
      the predominant source of indoor PAHs. Total cancer risk of 8-10years old
      children exceeded (up to 22 times) USEPA recommended guideline of 10-6, and 7-87
      times WHO health-based threshold of 10-5. Risk due to indoor exposure in schools
      was 2-10 times higher than outdoors, mainly because of the higher amount of time
      that students spent indoors.

PMID- 27693149
TI  - Bacteria in drinking water sources of a First Nation reserve in Canada.
AB  - Approximately 20% of the 600 First Nations reserves across Canada are under a
      drinking water advisory, often due to unacceptable levels of bacteria. In this
      study, we detected fecal bacteria at an alarmingly high frequency in drinking
      water sources in a fly-in First Nations community, most notably in buckets/drums
      of homes without running water where Escherichia coli levels ranged from 20 to
      62,000CFU/100mL. The water leaving the water treatment plant was free of E. coli
      and its free residual chlorine concentration (0.67mg/L) was within the range
      typically observed for treated water in Canada. Water samples from taps in homes
      served by cisterns, and those sampled from the water truck and community
      standpipe, always showed unacceptable levels of E. coli (1 to 2100CFU/100mL) and
      free residual chlorine concentrations below the 0.2mg/L required to prevent
      bacterial regrowth. Samples from taps in homes served by piped water had lower
      levels of E. coli (0 to 2CFU/100mL). DNA- and RNA-based 16S rRNA Illumina
      sequencing demonstrated that piped and cisterns water distribution systems showed
      an abundance of viable cells of Alphaproteobacteria indicative of biofilm
      formation in pipes and cisterns. The alpha diversity, based on observed OTUs and
      three other indices, was lowest in water truck samples that supplied water to the
      cistern and the low free residual chlorine concentration (0.07mg/L) and
      predominance of Betaproteobacteria (63% of viable cells) that were immediately
      detected after the truck had filled up at the water treatment plant was
      indicative of contamination by particulate matter. Given these findings, First
      Nation residents living without running water and relying on inadequate water
      distribution systems are at higher risk of contracting water-born illnesses. We
      urge all governments in Canada to expand their investments in supporting and
      sustaining water as a human right in Canada's First Nations communities.

PMID- 27693150
TI  - Low-cost sensors and crowd-sourced data: Observations of siting impacts on a
      network of air-quality instruments.
AB  - Low-cost sensors offer the possibility of gathering high temporal and spatial
      resolution crowd-sourced data-sets that have the potential to revolutionize the
      ways in which we understand individual and population exposure to air pollution.
      However, one of the challenges associated with crowd-sourced data ('citizen
      science'), often from low-cost sensors, is that citizens may use sites strongly
      affected by local conditions, limiting the wider significance of the data. This
      paper examines results from a low-cost network measuring ground-level ozone to
      evaluate the impact of siting on data quality. Locations at both reference
      stations and at private homes or research centers were used, and thought of as a
      typical 'crowd-sourced' network. Two instruments were co-located at each site to
      determine intra-site variability and evaluated by standard performance statistics
      and local-scale activity logs. The wider application of the data for both
      regional Inter-site variability was evaluated to show-case the wider value and
      usefulness of crowd-sourced data. Analysis of intra-site variability showed
      little differences at most sites (<5ppb). Large differences in intra-site
      variability were detected when sensors were exposed to direct sunlight (causing
      thermal variations within the instrument) and proximity to large emission
      sources. Short-term local activities, such as lawn-mowing, were identifiable in
      the data, but had minimal impact on standard reporting time-scales, and so did
      not pose as being significant limitations or errors. Inter-site evaluation
      demonstrated that dense networks of low-cost sensors can add value to existing
      networks, with minimal impact on the overall data-set quality. Sensors located in
      crowd-sourced locations nearby to regulatory analyzers were able to capture
      similar trends and concentrations, supporting their ability to report on wider
      conditions. Thus crowd-sourced approaches to monitoring (with suitable
      calibration and data quality control checks) may be an appropriate method for
      increasing the temporal and spatial resolution of air quality networks.

PMID- 27693151
TI  - Deforestation impacts on soil organic carbon stocks in the Semiarid Chaco Region,
      Argentina.
AB  - Land use change affects soil organic carbon (SOC) and generates CO2 emissions.
      Moreover, SOC depletion entails degradation of soil functions that support
      ecosystem services. Large areas covered by dry forests have been cleared in the
      Semiarid Chaco Region of Argentina for cropping expansion. However, deforestation
      impacts on the SOC stock and its distribution in the soil profile have been
      scarcely reported. We assessed these impacts based on the analysis of field data
      along a time-since-deforestation-for-cropping chronosequence, and remote sensing
      indices. Soil organic C was determined up to 100cm depth and physically
      fractionated into mineral associated organic carbon (MAOC) and particulate
      organic C (POC). Models describing vertical distribution of SOC were fitted.
      Total SOC, POC and MAOC stocks decreased markedly with increasing cropping age.
      Particulate organic C was the most sensitive fraction to cultivation. After 10yr
      of cropping SOC loss was around 30%, with greater POC loss (near 60%) and smaller
      MAOC loss (near 15%), at 0-30cm depth. Similar relative SOC losses were observed
      in deeper soil layers (30-60 and 60-100cm). Deforestation and subsequent cropping
      also modified SOC vertical distribution. Soil organic C loss was negatively
      associated with the proportion of maize in the rotation and total crop biomass
      inputs, but positively associated with the proportion of soybean in the rotation.
      Without effective land use polices, deforestation and agricultural expansion can
      lead to rapid soil degradation and reductions in the provision of important
      ecosystem services.

PMID- 27693152
TI  - Effects of experimental throughfall reduction and soil warming on fine root
      biomass and its decomposition in a warm temperate oak forest.
AB  - Fine root dynamics play a critical role in regulating carbon (C) cycling in
      terrestrial ecosystems. Examining responses of fine root biomass and its
      decomposition to altered precipitation pattern and climate warming is crucial to
      understand terrestrial C dynamics and its feedback to climate change. Fine root
      biomass and its decomposition rate were investigated in a warm temperate oak
      forest through a field manipulation experiment with throughfall reduction and
      soil warming conducted. Throughfall reduction significantly interacted with soil
      warming in affecting fine root biomass and its decomposition. Throughfall
      reduction substantially increased fine root biomass and its decomposition in
      unheated plots, but negative effects occurred in warmed plots. Soil warming
      significantly enhanced fine root biomass and its decomposition under ambient
      precipitation, but the opposite effects exhibited under throughfall reduction.
      Different responses in fine root biomass among different treatments could be
      largely attributed to soil total nitrogen (N), while fine root decomposition rate
      was more depended on microbial biomass C and N. Our observations indicate that
      decreased precipitation may offset the positive effect of soil warming on fine
      root biomass and decomposition.

PMID- 27693153
TI  - Biochar applied with appropriate rates can reduce N leaching, keep N retention
      and not increase NH3 volatilization in a coastal saline soil.
AB  - The impacts of biochar addition on nitrogen (N) leaching, (ammonia) NH3
      volatilization from coastal saline soils are not well understood. In this soil
      column study, the effects of wheat straw biochar application at rates of 0.5%,
      1%, 2% and 4% by weight to a coastal saline soil on N leaching, NH3
      volatilization, soil pH and N retention were investigated. Results showed that
      0.5% and 1% biochar amendments reduce the NH4+-N, NO3--N and total N
      concentrations of leachate and thereby significantly decrease their cumulative
      lost loads by 11.6-24.0%, 13.2-29.7%, and 14.6-26.0%, respectively, in compared
      with the control. The biochar-induced soil N leaching mitigation efficiency was
      weakened when the biochar application rates increased to 2% and 4%. However, the
      impact of biochar addition on cumulative NH3 volatilizations were negative and
      significantly 25.6-53.6% higher NH3 volatilizations in soils with 2% and 4%
      biochar amended than control were detected, which was mainly attributed to the
      averaged 0.53-0.88units higher soil pH as results of biochar addition. On
      average, the total N concentrations of soil were kept same with 1.01-1.06gkg-1
      under control and biochar treatments. Therefore, biochar application to the
      coastal saline soils with appropriate rates (i.e., 0.5% and 1% in current study)
      can reduce N leaching, keep soil N retention, and not increase NH3
      volatilization, which was beneficial for sustainable use of saline soils.

PMID- 27693154
TI  - Tracking the route of phenanthrene uptake in mosses: An experimental trial.
AB  - In recent decades, mosses have been used as native species or as transplants in
      monitoring a wide range of pollutants from inorganic (i.e. metals and metalloids)
      to organic contaminants (mainly polycyclic aromatic hydrocarbons-PAHs). To
      implement the use of mosses as biomonitors of PAHs, one important issue is the
      study of the interactions between these compounds and moss tissues. In this study
      we investigated the mode of phenanthrene uptake in four moss species
      (Amblystegium humile, Plagiomnium affine, Hypnum cupressiforme and a clone of
      Sphagnum palustre) and its movements from air to plant surface and within the
      biomonitors, using fluorescent and confocal microscopy. The target compound,
      partitioned between gas and particulate phase depending on air conditions, was
      selected since it is one of the most abundant PAHs released into the atmosphere.
      Our findings support the hypothesis that phenanthrene aggregates in particles and
      in this form it is chiefly intercepted and uptaken onto moss surfaces, albeit
      with different frequency in the four species, with S. palustre>H.
      cupressiforme>P. affine=A. humile. Phenanthrene enters the dead, empty hyalocysts
      of S. palustre. Specific surface area and composition, frequency and distribution
      of binding groups may also explain the different ability of phenanthrene uptake
      by the four moss species.

PMID- 27693155
TI  - The application of Diffusive Gradients in Thin Films (DGT) for improved
      understanding of metal behaviour at marine disposal sites.
AB  - Assessment of the effects of sediment metal contamination on biological
      assemblages and function remains a key question in marine management, especially
      in relation to disposal activities. However, the appropriate description of
      bioavailable metal concentrations within pore-waters has rarely been reported.
      Here, metal behaviour and availability at contaminated dredged material disposal
      sites within UK waters were investigated using Diffusive Gradient in Thin films
      (DGT). Three stations, representing contrasting history and presence of dredge
      disposal were studied. Depth profiles of five metals were derived using DGT
      probes as well as discrete analysis of total metal concentrations from sliced
      cores. The metals analysed were: iron and manganese, both relevant to sediment
      biogeochemistry; cadmium, nickel and lead, classified as priority pollutants. DGT
      time-integrated labile flux profiles of the metals display behaviour consistent
      with increasingly reduced conditions at depth and availability to DGT (iron and
      manganese), subsurface peaks and a potential sedimentary source to the water
      column related to the disposal activity (lead and nickel) and release to pore
      water linked to decomposition of enriched phytodetritus (cadmium). DGT data has
      the potential to improve our current understanding of metal behaviour at impacted
      sites and is suitable as a monitoring tool. DGT data can provide information on
      metal availability and fluxes within the sediment at high depth-resolution (5mm
      steps). Differences observed in the resulting profiles between DGT and
      conventional total metal analysis illustrates the significance of considering
      both total metals and a potentially labile fraction. The study outcomes can help
      to inform and improve future disposal site impact assessment, and could be
      complemented with techniques such as Sediment Profile Imagery for improved
      biologically relevance, spatial coverage and cost-effective monitoring and
      sampling of dredge material disposal sites. Additionally, the application of this
      technology could help improve correlative work on biological impacts under
      national and international auspices when linking biological effects to more
      biologically relevant metal concentrations.

PMID- 27693156
TI  - Refining correction factors for back-calculation of illicit drug use.
AB  - The estimation of illicit drugs use through wastewater analysis has become an
      important issue in the last few years due to their large worldwide consumption,
      which results in economic, social and health costs. The amounts of urinary
      biomarkers of illicit drugs (selected drugs or their metabolites) measured in
      wastewater are used to back-calculate the consumption of a particular drug by the
      population and to monitor temporal and spatial trends of illicit drug use in a
      community. The reliability of back-calculation depends on different factors, one
      being the accuracy of correction factors. A wide range of correction factors have
      been used in different studies and some biases must be expected when comparing
      results. Most of the correction factors were developed several years ago, so they
      need to be updated to include the latest information on pharmacokinetics.
      Moreover, new comprehensive methods to treat data should be adopted. The goal of
      this study is to refine current correction factors for back-calculation of the
      most widely used illicit drugs: amphetamine, methamphetamine, 3,4
      methylenedioxymethamphetamine (MDMA) and tetrahydrocannabinol (THC). The mean
      percentages of excretion of the parent drugs and their metabolites were
      calculated for each route of administration, utilizing all accessible
      pharmacokinetic studies in the literature. This allowed to select the most
      suitable drug target residue and a refined correction factor was obtained for
      each substance considering the most frequent route of administration. The refined
      correction factors we propose can be used in wastewater based epidemiology to
      standardize the back-calculation of these drugs. These results can be included in
      the best practice protocol currently adopted in EU studies in order to reduce
      uncertainty and improve the comparability of results.

PMID- 27693157
TI  - Short- and medium-chain chlorinated paraffins in sediments from the middle
      reaches of the Yangtze River: Spatial distributions, source apportionment and
      risk assessment.
AB  - Chlorinated paraffins (CPs) are easily adsorbed into sediments where they pose
      potential risks to the ecosystem and human health. Few studies have investigated
      short- and medium-chain CPs (SCCPs and MCCPs) in sediments. The aim of the
      present study was to comprehensively investigate contamination levels, spatial
      distributions, sources and risks posed by CPs in sediments from the middle
      reaches of the Yangtze River. The sediment samples were analyzed by two
      dimensional gas chromatography coupled with time-of-flight mass spectrometry
      (GC*GC-TOFMS). The concentrations of SCCPs and MCCPs ranged from 4.19 to 41.6ng/g
      dry weight (dw) and not detected to 14.6ng/g dw, respectively. No significant
      correlation was found between the total organic carbon contents and CP
      concentrations (P>0.05). The spatial distributions showed that CP contamination
      levels in the sediments were related to local human activities. The dominant
      congener groups were C10-11Cl6-7 for SCCPs, and C14Cl7-8 for MCCPs.
      Correspondence analysis revealed that likely sources of SCCPs were the production
      and use of CP-42 and CP-52. Principal component analysis indicated that SCCPs and
      MCCPs in the sediments may come from different sources. Moreover, CPs with nine
      carbon atoms were quantitated for the first time in sediment samples, and the
      results indicated they should not be neglected in future analyses. Risk
      assessments indicated that CPs in the sediments did not pose a great ecological
      risk currently.

PMID- 27693158
TI  - Telomere damage and redox status alterations in free-living passerines exposed to
      metals.
AB  - Telomere length may reflect the expected life span and possibly individual
      quality. Environmental stressors are known to increase oxidative stress and
      accelerate telomere attrition: however the interactions between redox status and
      telomere dynamics are not fully understood. We investigated whether exposure to
      heavy metal pollution is associated with oxidative stress and telomere damage in
      two insectivorous passerines, the Great tit (Parus major) and the Pied flycatcher
      (Ficedula hypoleuca). We were also interested to know whether within-brood
      competition could influence the nestling redox status or telomere length.
      Breeding females and nestlings were sampled near the point pollution source and
      compared to birds in non-polluted control zone. We measured heavy metal
      concentrations, calcium, metallothioneins, telomere lengths and redox status
      (oxidative damage, and enzymatic and non-enzymatic antioxidants) in liver
      samples. Great tit nestlings in the polluted zone had significantly shorter
      telomeres compared to those in the unpolluted control zone. In addition, those
      great tit nestlings that were lighter than their average siblings, had shorter
      telomeres compared to the heavier ones. In pied flycatchers neither pollution nor
      growth stress were associated with telomere length, but adult females had
      significantly shorter telomeres compared to the nestlings. All the results
      related to redox status varied remarkably among the species and the age groups.
      In both species antioxidants were related to pollution. There were no significant
      associations between redox status and telomere length. Our results suggest that
      wild birds at a young age are vulnerable to pollution and growth stress induced
      telomere damage. Redox status seems to interact with pollution and growth, but
      more studies are needed to clarify the underlying physiological mechanisms of
      telomere attrition. Our study highlights that all the observed associations and
      differences between the sampling zones varied depending on the species, age, and
      degree of exposure to pollution.

PMID- 27693159
TI  - Effects of etching time on alpha tracks in solid state nuclear track detectors.
AB  - Solid State Nuclear Track Detectors (SSNTDs) are used extensively for monitoring
      alpha particle radiation, neutron flux and cosmic ray radiation. Radon gas
      inhalation is regarded as being a significant contributory factor to lung cancer
      deaths in the UK each year. Gas concentrations are often monitored using CR39
      based SSNTDs as the natural decay of radon results in alpha particles which form
      tracks in these detectors. Such tracks are normally etched for about 4h to enable
      microscopic analysis. This study examined the effect of etching time on the
      appearance of alpha tracks in SSNTDs by collecting 2D and 3D image datasets using
      laser confocal microscope imaging techniques. Etching times of 2 to 4h were
      compared and marked differences were noted in resultant track area. The median
      equivalent diameters of tracks were 20.2, 30.2 and 38.9MUm for etching at 2, 3
      and 4h respectively. Our results indicate that modern microscope imaging can
      detect and image the smaller size tracks seen for example at 3h etching time.
      Shorter etching times may give rise to fewer coalescing tracks although there is
      a balance to consider as smaller track sizes may be more difficult to image. Thus
      etching for periods of less than 4h clearly merits further investigation as this
      approach has the potential to improve accuracy in assessing the number of tracks.

PMID- 27693160
TI  - Effect of magnetite nanoparticles on the germination and early growth of Quercus
      macdougallii.
AB  - The present study measures the effect of citrate-coated magnetite nanoparticles
      (Fe3O4-NPs) on the germination and early growth of Quercus macdougallii (oak).
      Two types of Fe3O4-NPs were synthetized and characterized, being denominated NP1
      and NP2. The synthesis was performed by the co-precipitation method and partial
      reduction of iron(II), respectively. It was found that the NP1 has a quasi
      spherical morphology, with sizes of 6-10nm, while the NP2 has sizes between 65
      and 160nm. It was demonstrated that the Fe3O4-NPs exhibit peroxidase-like
      catalytic activity. Experiments of germination and growth of Quercus macdougallii
      were performed using the synthesized Fe3O4-NPs treatments and a deionized water
      control. The experiments were performed in intact and peeled acorns. The
      application of the NPs increased the germination up to 33% in relation to the
      control. Additionally, the Fe3O4-NPs treatments increased the growth, dry
      biomass, and chlorophyll concentration. The data obtained in this study suggest
      that Fe3O4-NPs treatments could be potentially used to improve conservation and
      reforestation of threatened forestry species.

PMID- 27693161
TI  - Hepatitis B virus genetic diversity has minimal impact on sensitivity of the
      viral ribonuclease H to inhibitors.
AB  - Hepatitis B virus (HBV) causes hepatitis, cirrhosis, liver failure, and liver
      cancer, but the current therapies that employ either nucelos(t)ide analogs or
      (pegylated)interferon alpha do not clear the infection in the large majority of
      patients. Inhibitors of the HBV ribonuclease H (RNaseH) that are being developed
      with the goal of producing anti-HBV drugs are promising candidates for use in
      combination with the nucleos(t)ide analogs to improve therapeutic efficacy. HBV
      is genetically very diverse, with at least 8 genotypes that differ by >=8% at the
      sequence level. This diversity is reflected in the viral RNaseH enzyme, raising
      the possibility that divergent HBV genotypes or isolates may have varying
      sensitivity to RNaseH inhibitors. To evaluate this possibility, we expressed and
      purified 18 patient-derived RNaseHs from genotypes B, C, and D. Basal RNaseH
      activity and sensitivity to three novel RNaseH inhibitors from three different
      chemotypes were assessed. We also evaluated four consensus HBV RNaseHs to
      determine if such sequences would be suitable for use in antiviral drug
      screening. The patient-derived enzymes varied by over 10-fold in their basal
      RNaseH activities, but they were equivalently sensitive to each of the three
      inhibitors. Similarly, all four consensus HBV RNaseH enzymes were active and were
      equally sensitive to an RNaseH inhibitor. These data indicate that a wide range
      of RNaseH sequences would be suitable for use in antiviral drug screening, and
      that genotype- or isolate-specific genetic variations are unlikely to present a
      barrier during antiviral drug development against the HBV RNaseH.

PMID- 27693162
TI  - [Reduction of rehospitalisation on elderly heart failure patients: A
      retrospective cohort VISage network].
AB  - BACKGROUND: Heart failure was a public health problem for one million of French
      patients. Patients are particularly concerned in rehospitalisation for this
      chronic pathology. A specific healthcare network was created to take care of
      patients with heart failure directly at home. This healthcare network (named
      VISage) brings a specific and adapted monitoring in heart failure. The main of
      this study was to evaluate the impact of healthcare network in rehospitalisation
      rate for heart failure of patients. MATERIAL AND METHODS: We conducted a
      retrospective cohort study with patients' hospital files of the CH Vienne.
      Patients who were included in our healthcare network (VISage) were screened.
      Primary endpoint was 30days, 6 months, and 1year rehospitalisation rate for heart
      failure before and after using healthcare network. RESULTS: One hundred and four
      patients with comorbidities were included between February 2009 and November
      2015. A significant reduction of rehospitalisation rate for heart failure was
      observed before and after network: 0.65 (+/-0.52) vs. 0.17 (+/-0.43) 30days, 1.17
      (+/-0.74) vs. 0.42 (+/-0.71) at 6 months and 1.35 (+/-0.95) vs. 0.47 (+/-0.74) at
      1 year (P<0.0001). Results were significant for global rehospitalisation rate
      too. No significant differences were shown on hospital length of stay.
      CONCLUSION: Coordinated healthcare by a specific network at home for elderly is
      benefic for the rehospitalisation rate.

PMID- 27693163
TI  - [Usefulness of natriuretic peptide testing and Doppler echocardiography at
      bedside in the diagnosis of acute heart failure].
AB  - Acute heart failure is a common condition that leads to hospital admission, with
      important mortality and readmission rates. A prompt and accurate diagnosis of
      this condition by hospitalists is essential for an early and tailored medical
      management. The use of natriuretic peptide testing (BNP and NT-proBNP) through a
      two cut-point strategy is currently recommended as the first-line diagnostic
      complement to the initial clinical evaluation in the acute care setting.
      Transthoracic Doppler echocardiography is an other noninvasive method that can be
      used at bedside, especially in patients with intermediate, inconclusive
      natriuretic peptides levels. In this regard, left ventricular ejection fraction
      and several simple Doppler indexes (restrictive mitral filling pattern, spectral
      tissue Doppler E/e' ratio), have been validated in the emergency diagnosis of
      acute heart failure. The aim of the present review is to overview the respective
      contribution of natriuretic peptides and Doppler echocardiography at bedside to
      the diagnosis of acute heart failure in the acute care setting.

PMID- 27693164
TI  - [Outpatient management of pulmonary embolism diagnosed in emergency services].
AB  - In the emergency department, the management of patients with pulmonary embolism
      depends on the early mortality risk. Outpatient care is possible in low-risk
      patients. We present the existing scores and the strategy proposed by the North
      Alps Emergency Network, which uses the simplified PESI score (Pulmonary Embolism
      Severity Index) to select those low-risk patients, candidates for early
      discharge.

PMID- 27693165
TI  - [Fast track chest pain pathway in emergency department].
AB  - Acute chest pain is a common reason of consultation in the emergency department.
      The difficulty lies in discriminating patients with acute coronary syndrome or
      other life-threatening conditions from those non-cardiovascular, non-life
      threatening chest pain. Only 15 to 25 % of patients with acute chest pain
      actually have acute coronary syndrome. Algorithms using high sensitivity troponin
      at admission and a second assessment 1 or 3hours later are validated to "rule in"
      or "rule out" the diagnosis of non ST-elevation myocardial infarction. This may
      reduce the delay for the diagnosis translating into shorter stay in the emergency
      department. Those algorithms must be interpreted in the context of clinical and
      ECG criteria.

PMID- 27693166
TI  - [Intracoronary administration of antithrombotic agents via a perfusion balloon
      catheter in patients with ST-segment elevation myocardial infarction presenting
      with massive intraluminal thrombus and failed aspiration].
AB  - BACKGROUND: Massive intracoronary thrombus is associated with adverse procedural
      results including failed aspiration and unfavourable reperfusion. We aim to
      evaluate the effect of the intracoronary administration of antithrombotic agents
      via a perfusion catheter in patients with ST-segment elevation myocardial
      infarction (STEMI) presenting with a large thrombus burden and failed aspiration.
      METHODS: We retrospectively analyzed the thrombus burden, the TIMI grade flow,
      and the myocardial Blush in 25 consecutive STEMI patients with a large thrombus
      burden and failed manual aspiration, who received intracoronary infusion of
      glycoprotein IIb/IIIa inhibitors (N=17) or bivalirudine (N=8) via a 6F-infusion
      catheter (ClearWayTM RX) RESULTS: Mean age was 67+/-14 years, 16 patients (64 %)
      presented with anterior STEMI, and 7 (28 %) with cardiogenic shock. Immediately
      after intracoronary infusion, the TIMI flow grade improved of 2 grades in 7
      patients (28 %), and 1 grade in 14 (56 %), a complete resolution of the thrombus
      was observed in 9 patients, and a >50 % resolution in 12. Blush was improved of 3
      grades in 15 patients (60 %), of 2 grades in 7 (28 %), and Blush grade 0 remained
      in 3. At the end of procedure, we observed normal TIMI 3flow in most patients (92
      %), a complete resolution of thrombus in 80 %, and a Blush grade 3 in 68 %.
      CONCLUSIONS: In STEMI patients presenting with a large thrombus burden and failed
      aspiration, intracoronary administration of glycoprotein IIb/IIIa inhibitors or
      bivalirudin via the perfusion catheter ClearWayTM RX significantly reduced the
      thrombus burden and improved the TIMI flow and the Blush grade, without bleeding.

PMID- 27693167
TI  - [Safety of device implantation under antipatelet therapy with ticagrelor: About
      20 cases].
AB  - INTRODUCTION: Management of antiplatelet therapy at the time of device
      implantation remains controversial. This study aimed to assess the risk of
      bleeding complications in patients receiving ticagrelor at the time of cardiac
      device surgery. METHODS: We performed a multicentre (n=4), retrospective study
      from January 2015 to January 2016. The survey included all patients (pts) treated
      with ticagrelor before undergoing pacemaker, implantable cardioverter
      defibrillator (ICD) implantation or generator replacement. We report hemorrhagic
      post-procedural complications at 1 month. A significant bleeding complication was
      defined as pocket hematoma requiring a surgical evacuation or prolonged
      hospitalization, hemothorax, pericardial effusion, or tamponade. RESULTS: A total
      of 20 patients underwent a permanent pacemaker or ICD implantation while taking a
      combination of antipatelet therapy with ticagrelor and aspirin. The mean age of
      the patients was 65+/-9 years, 95% were male, 25% of patients were diabetics, 55%
      had hypertension and 50% presented a history of heart failure. All the patients
      had a history of acute coronary syndrome [6 (4-26) months before the procedure].
      The majority of implanted devices were ICDs (17, 85%) with 5 single chamber, 4
      dual chambers and 9 triple chambers ICDs. Subclavian venous approach was utilized
      in 9 patients. The mean duration of procedure was 60minutes. One per-procedure
      bleeding was described due to high venous pressure, without post-procedure
      hematoma. A post-procedure pocket hematoma has been experienced by one patient.
      The subclavian approach was used for the 2 patients. No blood transfusion was
      needed for these 2 cases. CONCLUSION: Ticagrelor treatment at the time of heart
      rhythm device procedures does not seem to be associated with an increased risk of
      significant bleeding complications. In our study, 2 patients experienced
      nonsignificant bleeding complications.

PMID- 27693168
TI  - [Cardiac permanent pacemaker after transcatheter aortic valve implantation: A
      predictive and scientific review].
AB  - Transcatheter aortic valve implantation (TAVI) is nowadays a worldwide technique
      in the field of treating aortic stenosis. One of the main side effects linked to
      the technique are mostly attached to rhythm disturbances, such as
      atrioventricular (AV) and intraventricular blocks. Consequently, a pacemaker
      implantation is often required. That implantation rate is estimated between 8 and
      30%, depending on the valve chosen. Thanks to main meta analysis on the subject,
      it has been managed to isolate the following risks factors for AV block
      development: preoperative right bundle branch block (RBBB: the most powerful
      element), complete AV block during the procedure, male gender, a so-called
      porcelain aorta, the absence of previous valvular surgery, the aortic annulus
      size (i.e when that size is inferior to the valve's one) and the QRS duration
      after the procedure (the superior threshold has been set at 128ms for the
      Corevalve). The currently recommendations advice to implant a pacemaker are as
      followed: high grade AV block (in the main studies, the implantation occurs
      within the 5 days after the TAVI), complete and transient AV block during the
      TAVI, second degree AV block and RBBB associated with first degree AV block. Our
      article aims to review the arrhythmic issues of TAVI.

PMID- 27693169
TI  - [Troponin elevation in the absence of acute coronary syndrome].
AB  - Cardiac troponins are the most sensitive and specific markers of myocardial
      injury. Cardiac troponin elevation are common in many diseases and do not
      necessarily indicate the presence of a thrombotic acute coronary syndrome. In
      clinical practice, interpretation of dynamic changes of troponin may be
      challenging. Troponin evaluation should be performed only if clinically indicated
      and must be interpreted in the context of clinical presentation, ECG changes,
      troponin level and kinetic. In the absence of thrombotic acute coronary syndrom,
      troponin retains a prognostic value. Its practical interest as a risk criteria is
      limited to a few situations like pulmonary embolism, pericarditis an myocarditis.

PMID- 27693170
TI  - Preclinical study investigating the potential of low-dose-rate brachytherapy with
      32P stents for the prevention of restenosis of paranasal neo-ostia.
AB  - PURPOSE: Ostial restenosis is a common cause of failures in paranasal sinus
      surgery. The aim of the current study was to investigate the use of low-dose-rate
      brachytherapy to prevent neo-ostial restenosis in an animal model. METHODS AND
      MATERIALS: In 14 rabbits, maxillary neo-ostia were created and measured. One side
      each was stented with a regular silicone stent, the other side was either not
      stented (n = 7) or stented with a phosphorous-32 implanted stent depositing a low
      dose radiation of 15 Gy (n = 7) within 1 week, after which all stents were
      removed. After a period of additional 12 weeks of recovery, the animals were
      sacrificed, the neo-ostia were again measured, and the areas and histopathologic
      changes compared in between the groups. RESULTS: After 15-Gy stenting, the mean
      ostial areas were even slightly enlarged by 5.1% compared to the area at stent
      removal, whereas a significant reduction in area, indicating a process of
      restenosis, by 56.1% or 54.0% was seen in the control groups with no stent and
      normal stent, respectively. Furthermore, no indication for adverse
      histopathologic radiation effects was seen in the 15-Gy group. CONCLUSIONS: Low
      dose-rate brachytherapy with phosphorous-32 doped silicone stents showed
      promising results in the prevention of neo-ostium restenosis in this proof-of
      concept study, indicating that further preclinical and clinical testing may be
      warranted.

PMID- 27693171
TI  - The dosimetric impact of air in vaginal vault brachytherapy.
AB  - PURPOSE: Vaginal vault brachytherapy is an adjuvant treatment to reduce risk of
      local recurrence in endometrial cancer. Axial imaging has demonstrated the
      presence of air gaps between the surface of a cylindrical applicator and mucosal
      wall. The impact of these on dosimetry and applicability of the TG-43 formalism
      in the presence of air has been assessed. METHODS AND MATERIALS: The planning CT
      scans for a retrospective sample of 82 patients were examined for the presence of
      air gaps. These were quantified in terms of the radial and longitudinal aspect
      with reference to the applicator, frequency per patient, and location along the
      applicator. Monte Carlo calculations and ionization chamber measurements were
      made in a phantom to estimate the uncertainty of the TG-43 algorithm. RESULTS:
      The overall incidence of air gaps was 91.4%. The most common radial size was
      between 2 and 3 mm (43.0%) that resulted in an average dose reduction of 14.8%.
      There is a strong correlation between radial dimension and TG-43 calculated dose
      reduction. Monte Carlo simulations and phantom measurements indicated that the
      inhomogeneity resulted in a maximum of 2.4% deviation from doses calculated using
      TG-43. CONCLUSIONS: Air gaps are common. TG-43 formalism is not significantly
      compromised by the presence of air. However, the presence of the air does produce
      a displacement of the mucosal surface away from the applicator and this causes a
      significant dose reduction.

PMID- 27693172
TI  - Combining transrectal ultrasound and CT for image-guided adaptive brachytherapy
      of cervical cancer: Proof of concept.
AB  - PURPOSE: To investigate the feasibility of a treatment planning workflow for
      three-dimensional image-guided cervix cancer brachytherapy, combining volumetric
      transrectal ultrasound (TRUS) for target definition with CT for dose optimization
      to organs at risk (OARs), for settings with no access to MRI. METHODS AND
      MATERIALS: A workflow for TRUS/CT-based volumetric treatment planning was
      developed, based on a customized system including ultrasound probe, stepper unit,
      and software for image volume acquisition. A full TRUS/CT-based workflow was
      simulated in a clinical case and compared with MR- or CT-only delineation. High
      risk clinical target volume was delineated on TRUS, and OARs were delineated on
      CT. Manually defined tandem/ring applicator positions on TRUS and CT were used as
      a reference for rigid registration of the image volumes. Treatment plan
      optimization for TRUS target and CT organ volumes was performed and compared to
      MRI and CT target contours. RESULTS: TRUS/CT-based contouring, applicator
      reconstruction, image fusion, and treatment planning were feasible, and the full
      workflow could be successfully demonstrated. The TRUS/CT plan fulfilled all
      clinical planning aims. Dose-volume histogram evaluation of the TRUS/CT-optimized
      plan (high-risk clinical target volume D90, OARs D2cm3 for) on different image
      modalities showed good agreement between dose values reported for TRUS/CT and MRI
      only reference contours and large deviations for CT-only target parameters.
      CONCLUSIONS: A TRUS/CT-based workflow for full three-dimensional image-guided
      cervix brachytherapy treatment planning seems feasible and may be clinically
      comparable to MRI-based treatment planning. Further development to solve
      challenges with applicator definition in the TRUS volume is required before
      systematic applicability of this workflow.

PMID- 27693173
TI  - Point A vs. HR-CTV D90 in MRI-based cervical brachytherapy of small and large
      lesions.
AB  - PURPOSE: To evaluate the dosimetric benefits of MRI-based brachytherapy in small
      and large high-risk clinical target volume (HR-CTV) in cervical cancer. METHODS
      AND MATERIALS: Twenty-eight fractions obtained from sixteen cervical cancer
      patients treated with MRI-based high-dose-rate brachytherapy with standard tandem
      and ovoid applicators were used; original fractions were optimized to HR-CTV D90.
      Fractions were separated based on the median volume into small and large (HR-CTV
      <25 cm3 or >25 cm3) lesion groups. Retrospective plans prescribed to Point A were
      created for each fraction. D0.1 cc, D2 cc, and International Commission of
      Radiation Unit and Measurements (ICRU) points were used to compare Point A vs. HR
      CTV D90 plans for bladder, rectum, and sigmoid. RESULTS: In the small lesion
      group, Point A plans vs. HR-CTV D90 plans had significantly higher D0.1 cc, D2
      cc, and ICRU points for bladder, rectum, and sigmoid (p < 0.05). In the large
      lesion group, there was no significant difference between Point A and HR-CTV D90
      plans for D0.1 cc, D2 cc, and ICRU points to the organs at risk (OARs).
      CONCLUSIONS: The dosimetric advantages to OARs offered by MRI-based brachytherapy
      with prescription to HR-CTV D90 compared to Point A is most distinct for patients
      with smaller HR-CTV (<25 cm3). This study demonstrates sufficient tumor coverage
      with lower doses to OARs in HR-CTV D90 vs. Point A plans in the small lesion
      group. These improvements were not seen in the large lesion group, indicating a
      lesser dosimetric advantage of HR-CTV D90 compared to Point A planning when the
      cervical lesion is >25 cm3. Incorporation of interstitial needles for patients
      with larger HR-CTV is likely the best method to decrease dose to OARs and improve
      tumor coverage.

PMID- 27693180
TI  - Epidemiology of extended-spectrum beta-lactamase (ESBL) producing Escherichia
      coli in Japan: Characteristics of community-associated versus healthcare
      associated ESBL E. coli.
AB  - Data on community-associated extended-spectrum beta-lactamase (ESBL)-producing
      Escherichia coli (CA-ESBLEC) infections in Japan are scarce. We compared the
      clinical and microbiological epidemiology of CA-ESBLEC infections with that of
      healthcare-associated-ESBLEC infections among 76 patients with ESBLEC infections.
      We identified a high prevalence (26%) of CA-ESBLEC infections in Japan; only a
      small proportion (15%) of patients with CA-ESBLEC infections had recent exposure
      to antibiotics.

PMID- 27693181
TI  - Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's
      disease.
AB  - INTRODUCTION: Amyloid imaging has been integrated into diagnostic criteria for
      Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer
      structures and amyloid-beta aggregates in autosomal dominant AD (ADAD) and
      sporadic AD is unclear. METHODS: Binding properties of different amyloid tracers
      were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1
      EDelta9 mutations, 13 sporadic AD, and 14 control cases. RESULTS: 3H-PIB, 3H
      florbetaben, 3H-AZD2184, and BTA-1 shared a high- and a varying low-affinity
      binding site in the frontal cortex of sporadic AD. AZD2184 detected another
      binding site (affinity 33 nM) in the frontal cortex of ADAD. The 3H-AZD2184 and
      3H-PIB binding were significantly higher in the striatum of ADAD compared to
      sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on 3H
      AZD84 binding followed by 3H-florbetaben and minimal on 3H-PIB. DISCUSSION: This
      study implies amyloid tracers of different structures detect different sites on
      amyloid-beta fibrils or conformations.

PMID- 27693182
TI  - Withdrawn: Plasma concentrations of free amyloid-beta cannot predict the
      development of Alzheimer's disease.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, DOI of original article:
      http://dx.doi.org/10.1016/j.jalz.2016.12.004. 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- 27693183
TI  - Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics
      analysis.
AB  - INTRODUCTION: The aim of this study was to (1) replicate previous associations
      between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and
      (2) identify novel associations between lipids, clinical AD diagnosis, disease
      progression and brain atrophy (left/right hippocampus/entorhinal cortex).
      METHODS: We performed untargeted lipidomic analysis on 148 AD and 152 elderly
      control plasma samples and used univariate and multivariate analysis methods.
      RESULTS: We replicated our previous lipids associations and reported novel
      associations between lipids molecules and all phenotypes. A combination of 24
      molecules classified AD patients with >70% accuracy in a test and a validation
      data set, and we identified lipid signatures that predicted disease progression
      (R2 = 0.10, test data set) and brain atrophy (R2 >= 0.14, all test data sets
      except left entorhinal cortex). We putatively identified a number of metabolic
      features including cholesteryl esters/triglycerides and phosphatidylcholines.
      DISCUSSION: Blood lipids are promising AD biomarkers that may lead to new
      treatment strategies.

PMID- 27693184
TI  - Which types of mental work demands may be associated with reduced risk of
      dementia?
AB  - INTRODUCTION: Previous studies have demonstrated that an overall high level of
      mental work demands decreased dementia risk. In our study, we investigated
      whether this effect is driven by specific mental work demands and whether it is
      exposure dependent. METHODS: Patients aged 75+ years were recruited from general
      practitioners and participated in up to seven assessment waves (every 1.5 years)
      of the longitudinal AgeCoDe study. Analyses of the impact of specific mental work
      demands on dementia risk were carried out via multivariate regression modeling (n
      = 2315). RESULTS: We observed a significantly lower dementia risk in individuals
      with a higher level of "information processing" (HR, 0.888), "pattern detection"
      (HR, 0.878), "mathematics" (HR, 0.878), and "creativity" (HR, 0.878). Yet,
      exposure-dependent effects were only significant for "information processing" and
      "pattern detection." DISCUSSION: Our longitudinal observations suggest that
      dementia risk may be reduced by some but not all types of mental work demands.

PMID- 27693186
TI  - The financial burden and health care utilization patterns associated with
      amnestic mild cognitive impairment.
AB  - INTRODUCTION: Individuals with amnestic mild cognitive impairment (aMCI) are at
      elevated risk of developing Alzheimer's disease (AD) dementia. METHODS: With data
      from the Aging, Demographics, and Memory Study, we used the Clinical Dementia
      Rating Sum of Boxes classifications to conduct a cross-sectional analysis
      assessing the relationship between cognitive state and various direct and
      indirect costs and health care utilization patterns. RESULTS: Patients with aMCI
      had less medical expenditures than patients with moderate and severe AD dementia
      (P < .001) and were also significantly less likely to have been hospitalized (P =
      .04) and admitted to nursing home (P < .001). Compared to individuals with normal
      cognition, patients with aMCI had significantly less household income (P = .018).
      DISCUSSION: Patients with aMCI had lower medical expenditures than patients with
      AD dementia. Poor cognitive status was linearly associated with lower household
      income, higher medical expenditures, higher likelihood of nursing and home care
      services, and lower likelihood of outpatient visits.

PMID- 27693187
TI  - Subjective cognitive decline in cognitively normal elders from the community or
      from a memory clinic: Differential affective and imaging correlates.
AB  - INTRODUCTION: Subjective cognitive decline (SCD) could indicate preclinical
      Alzheimer's disease, but the existing literature is confounded by heterogeneous
      approaches to studying SCD. We assessed the differential cognitive, affective,
      and neuroimaging correlates of two aspects of SCD: reporting high cognitive
      difficulties on a self-rated questionnaire versus consulting at a memory clinic.
      METHODS: We compared 28 patients from a memory clinic with isolated SCD, 35
      community-recruited elders with similarly high levels of self-reported cognitive
      difficulties, and 35 community-recruited controls with low self-reported
      cognitive difficulties. RESULTS: Increased anxiety and amyloid beta deposition
      were observed in both groups with high self-reported difficulties, whereas
      subclinical depression and (hippocampal) atrophy were specifically associated
      with medical help seeking. Cognitive tests showed no group differences.
      DISCUSSION: These results further validate the concept of SCD in both community-
      and clinic-based groups. Yet, recruitment methods influence associated biomarkers
      and affective symptomatology, highlighting the heterogeneous nature of SCD
      depending on study characteristics.

PMID- 27693185
TI  - mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling
      promotes Alzheimer's disease.
AB  - A major obstacle to presymptomatic diagnosis and disease-modifying therapy for
      Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of
      AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark,
      but whether and how it might contribute to the synaptic dysfunction and neuron
      death that underlie memory and cognitive impairment has been mysterious. Neuron
      death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid-beta
      oligomers (AbetaOs) and tau, the precursors of plaques and tangles. We now report
      that CCR results from AbetaO-induced activation of the protein kinase complex,
      mTORC1, at the plasma membrane and mTORC1-dependent tau phosphorylation, and that
      CCR can be prevented by insulin-stimulated activation of lysosomal mTORC1.
      AbetaOs were also shown previously to reduce neuronal insulin signaling. Our data
      therefore indicate that the decreased insulin signaling provoked by AbetaOs
      unleashes their toxic potential to cause neuronal CCR, and by extension, neuron
      death.

PMID- 27693188
TI  - A common challenge in older adults: Classification, overlap, and therapy of
      depression and dementia.
AB  - Late-life depression is frequently associated with cognitive impairment.
      Depressive symptoms are often associated with or even precede a dementia
      syndrome. Moreover, depressive disorders increase the risk of persistence for
      mild cognitive impairment and dementia. Here, we present both the current state
      of evidence and future perspectives regarding the integration and value of
      clinical assessments, neuropsychological, neurochemical, and neuroimaging
      biomarkers for the etiological classification of the dementia versus the
      depression syndrome and for the prognosis of depression relating to dementia
      risk. Finally, we summarize the existing evidence for both pharmacotherapy and
      psychotherapy of depression in demented patients. There is an urgent need for
      large-scale collaborative research to elucidate the role and interplay of
      clinical and biological features in elderly individuals with depressive disorders
      who are at elevated risk for developing dementia. To overcome barriers for
      successful drug development, we propose the introduction of the precision
      medicine paradigm to this research field.

PMID- 27693189
TI  - Longitudinal brain structural changes in preclinical Alzheimer's disease.
AB  - INTRODUCTION: Brain structural changes in preclinical Alzheimer's disease (AD)
      are poorly understood. METHODS: We compared the changes in cortical thickness in
      the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD
      stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed
      the correlation between baseline CSF biomarkers and cortical atrophy rates.
      RESULTS: At follow-up, stage 1 subjects showed reduced atrophy rates in medial
      frontal areas and precuneus compared to stage 0 subjects, whereas stage 2/3
      subjects presented accelerated atrophy in medial temporal structures. Low CSF
      Abeta1-42 levels were associated with reduced atrophy rates in subjects with
      normal tau levels and high CSF tau levels with accelerated atrophy only in
      subjects with low Abeta1-42 levels. DISCUSSION: Our longitudinal data confirm a
      biphasic trajectory of changes in brain structure in preclinical AD. These have
      implications in AD trials, both in patient selection and the use of MRI as a
      surrogate marker of efficacy.

PMID- 27693190
TI  - Mastoparan is a membranolytic anti-cancer peptide that works synergistically with
      gemcitabine in a mouse model of mammary carcinoma.
AB  - Anti-cancer peptides (ACPs) are small cationic and hydrophobic peptides that are
      more toxic to cancer cells than normal cells. ACPs kill cancer cells by causing
      irreparable membrane damage and cell lysis, or by inducing apoptosis. Direct
      acting ACPs do not bind to a unique receptor, but are rather attracted to several
      different molecules on the surface of cancer cells. Here we report that an
      amidated wasp venom peptide, Mastoparan, exhibited potent anti-cancer activities
      toward leukemia (IC50~8-9.2MUM), myeloma (IC50~11MUM), and breast cancer cells
      (IC50~20-24MUM), including multidrug resistant and slow growing cancer cells.
      Importantly, the potency and mechanism of cancer cell killing was related to the
      amidation of the C-terminal carboxyl group. Mastoparan was less toxic to normal
      cells than it was to cancer cells (e.g., IC50 to PBMC=48MUM). Mastoparan killed
      cancer cells by a lytic mechanism. Moreover, Mastoparan enhanced etoposide
      induced cell death in vitro. Our data also suggest that Mastoparan and
      gemcitabine work synergistically in a mouse model of mammary carcinoma.
      Collectively, these data demonstrate that Mastoparan is a broad-spectrum, direct
      acting ACP that warrants additional study as a new therapeutic agent for the
      treatment of various cancers.

PMID- 27693191
TI  - Differentially expressed genes selection via Laplacian regularized low-rank
      representation method.
AB  - With the rapid development of DNA microarray technology and next-generation
      technology, a large number of genomic data were generated. So how to extract more
      differentially expressed genes from genomic data has become a matter of urgency.
      Because Low-Rank Representation (LRR) has the high performance in studying low
      dimensional subspace structures, it has attracted a chunk of attention in recent
      years. However, it does not take into consideration the intrinsic geometric
      structures in data. In this paper, a new method named Laplacian regularized Low
      Rank Representation (LLRR) has been proposed and applied on genomic data, which
      introduces graph regularization into LRR. By taking full advantages of the graph
      regularization, LLRR method can capture the intrinsic non-linear geometric
      information among the data. The LLRR method can decomposes the observation matrix
      of genomic data into a low rank matrix and a sparse matrix through solving an
      optimization problem. Because the significant genes can be considered as sparse
      signals, the differentially expressed genes are viewed as the sparse perturbation
      signals. Therefore, the differentially expressed genes can be selected according
      to the sparse matrix. Finally, we use the GO tool to analyze the selected genes
      and compare the P-values with other methods. The results on the simulation data
      and two real genomic data illustrate that this method outperforms some other
      methods: in differentially expressed gene selection.

PMID- 27693192
TI  - A snake-like serine proteinase (PmSnake) activates prophenoloxidase-activating
      system in black tiger shrimp Penaeus monodon.
AB  - Clip domain serine proteinases (ClipSPs) play critical roles in the activation of
      proteolytic cascade in invertebrate immune systems including the prophenoloxidase
      (proPO) activating system. In this study, we characterized a snake-like serine
      protease, namely PmSnake, from the shrimp Penaeus monodon which has previously
      been identified based on the subtractive cDNA library of proPO double-stranded
      RNA (dsRNA)-treated hemocytes. An open reading frame of PmSnake contains 1068 bp
      encoding a predicted protein of 355 amino acid residues with a putative signal
      peptide of 22 amino acids and two conserved domains (N-terminal clip domain and C
      terminal trypsin-like serine proteinase domain). Sequence analysis revealed that
      PmSnake was closest to the AeSnake from ant Acromyrmex echinatior (53%
      similarity), but was quite relatively distant from other shrimp PmclipSPs.
      PmSnake transcript was mainly expressed in shrimp hemocytes and up-regulated
      after systemic Vibrio harveyi infection indicating that it is an immune
      responsive gene. Suppression of PmSnake expression by dsRNA interference reduced
      both transcript and protein levels leading to a reduction of the hemolymph
      phenoloxidase (PO) activity (36%), compared to the control, suggesting that the
      PmSnake functions as a clip-SP in shrimp proPO system. Western blot analysis
      using anti-PmSnake showed that the PmSnake was detected in hemocytes but not in
      cell-free plasma. In vitro PO activity and serine proteinase activity assays
      showed that adding rPmSnake into the shrimp hemolymph could increase PO activity
      as well as serine proteinase activity suggesting that the rPmSnake activates the
      proPO system via serine proteinase cascade.

PMID- 27693193
TI  - Comparative transcriptomics in three ladybird species supports a role for
      immunity in invasion biology.
AB  - The spread of the invasive harlequin ladybird (Harmonia axyridis) in Europe is
      accompanied by the decline of the native and non-invasive two-spotted ladybird
      (Adalia bipunctata). Here we show that microsporidia carried by H. axyridis can
      kill A. bipunctata following the oral uptake of spores, suggesting that their
      horizontal transmission via intraguild predation may help the invader to
      outcompete its native competitor. The native seven-spotted ladybird (Coccinella
      septempunctata) is thought to be less susceptible both to the spread of H.
      axyridis and to its microsporidia. To investigate whether the distinct levels of
      pathogen susceptibility in these three ladybird species are determined by their
      immune systems, we compared the immunity-related transcriptomes of untreated
      beetles and beetles challenged with suspensions of bacteria and yeast. We found
      that H. axyridis carries three and four times as many genes encoding
      antimicrobial peptides representing the attacin, coleoptericin and defensin
      families than C. septempunctata and A. bipunctata, respectively. Gene expression
      studies following the injection of bacteria and yeasts into beetles revealed that
      members of these three antimicrobial peptide families are also induced more
      strongly in H. axyridis than C. septempunctata or A. bipunctata. Our results
      therefore support the hypothesis that a superior immune system promotes the
      performance of invasive species.

PMID- 27693195
TI  - Speech outcomes in Parkinson's disease after subthalamic nucleus deep brain
      stimulation: A systematic review.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in
      reducing motor symptoms for many individuals with Parkinson's disease (PD).
      However, STN DBS does not appear to influence speech in the same way, and may
      result in a variety of negative outcomes for people with PD (PWP). A high degree
      of inter-individual variability amongst PWP regarding speech outcomes following
      STN DBS is evident in many studies. Furthermore, speech studies in PWP following
      STN DBS have employed a wide variety of designs and methodologies, which
      complicate comparison and interpretation of outcome data amongst studies within
      this growing body of research. An analysis of published evidence regarding speech
      outcomes in PWP following STN DBS, according to design and quality, is missing.
      This systematic review aimed to analyse and coalesce all of the current evidence
      reported within observational and experimental studies investigating the effects
      of STN DBS on speech. It will strengthen understanding of the relationship
      between STN DBS and speech, and inform future research by highlighting
      methodological limitations of current evidence.

PMID- 27693194
TI  - Gait function and locus coeruleus Lewy body pathology in 51 Parkinson's disease
      patients.
AB  - INTRODUCTION: Gait impairment in Parkinson's Disease (PD) is often severely
      disabling, yet frequently remains refractory to treatment. The locus coeruleus
      (LC) has diffuse noradrenergic projections that are thought to play a role in
      gait function. Enhancement of norepinephrine transmission may improve gait in
      some PD patients. We hypothesized that the severity of PD pathology, and more
      specifically, Lewy bodies and neuronal loss in the LC, would correlate with the
      severity of gait dysfunction in PD. METHODS: Autopsy data from 51 patients,
      collected through the Morris K. Udall Parkinson's Disease Research Center, were
      correlated with clinical gait-related measures, including individual Unified
      Parkinson's Disease Rating Scale (UPDRS) Part II and III questions, total UPDRS
      Part III scores, and timed up-and-go speed (TUG). RESULTS: Neither the presence
      nor degree of Lewy body pathology in the LC on autopsy was associated with a
      higher UPDRS part III gait score. LC tau deposition and frontal Lewy body
      deposition were not correlated with any of the assessed gait measures. The degree
      of Lewy body pathology, independent of Braak stage, was positively associated
      with the severity of motor symptoms overall (UPDRS Part III total score).
      CONCLUSION: Neither the degree of Lewy body nor tau pathology in the LC is
      associated with severity of gait disorders in PD. This finding may have
      implications for targeted noradrenergic therapies in patients with refractory
      gait disorders.

PMID- 27693196
TI  - Operate or Medicate: Understanding Surgical Risks in the Elderly with
      Inflammatory Bowel Disease.

PMID- 27693197
TI  - Multiparametric imaging of brain hemodynamics and function using gas-inhalation
      MRI.
AB  - Diagnosis and treatment monitoring of cerebrovascular diseases routinely require
      hemodynamic imaging of the brain. Current methods either only provide part of the
      desired information or require the injection of multiple exogenous agents. In
      this study, we developed a multiparametric imaging scheme for the imaging of
      brain hemodynamics and function using gas-inhalation MRI. The proposed technique
      uses a single MRI scan to provide simultaneous measurements of baseline venous
      cerebral blood volume (vCBV), cerebrovascular reactivity (CVR), bolus arrival
      time (BAT), and resting-state functional connectivity (fcMRI). This was achieved
      with a novel, concomitant O2 and CO2 gas inhalation paradigm, rapid MRI image
      acquisition with a 9.3min BOLD sequence, and an advanced algorithm to extract
      multiple hemodynamic information from the same dataset. In healthy subjects, CVR
      and vCBV values were 0.23+/-0.03%/mmHg and 0.0056+/-0.0006%/mmHg, respectively,
      with a strong correlation (r=0.96 for CVR and r=0.91 for vCBV) with more
      conventional, separate acquisitions that take twice the scan time. In patients
      with Moyamoya syndrome, CVR in the stenosis-affected flow territories (typically
      anterior-cerebral-artery, ACA, and middle-cerebral-artery, MCA, territories) was
      significantly lower than that in posterior-cerebral-artery (PCA), which typically
      has minimal stenosis, flow territories (0.12+/-0.06%/mmHg vs. 0.21+/-0.05%/mmHg,
      p<0.001). BAT of the gas bolus was significantly longer (p=0.008) in ACA/MCA
      territories, compared to PCA, and the maps were consistent with the conventional
      contrast-enhanced CT perfusion method. FcMRI networks were robustly identified
      from the gas-inhalation MRI data after factoring out the influence of CO2 and O2
      on the signal time course. The spatial correspondence between the gas-data
      derived fcMRI maps and those using a separate, conventional fcMRI scan was
      excellent, showing a spatial correlation of 0.58+/-0.17 and 0.64+/-0.20 for
      default mode network and primary visual network, respectively. These findings
      suggest that advanced gas-inhalation MRI provides reliable measurements of
      multiple hemodynamic parameters within a clinically acceptable imaging time and
      is suitable for patient examinations.

PMID- 27693199
TI  - Induction of viral interference by IPNV-carrier cells on target cells: A cell co
      culture study.
AB  - IPNV is a salmonid birnavirus that possesses the ability to establish
      asymptomatic persistent infections in a number of valuable fish species. The
      presence of IPNV may interfere with subsequent infection by other viruses. In the
      present study we show that an IPNV-carrier cell line (EPCIPNV) can induce an
      antiviral state in fresh EPC by co-cultivating both cell types in three different
      ways: a "droplet" culture system, a plastic chamber setup, and a transmembrane
      (Transwell(r)) system. All three cell co-culture methods were proven useful to
      study donor/target cell interaction. Naive EPC cells grown in contact with
      EPCIPNV cells develop resistance to VHSV superinfection. The transmembrane system
      seems best suited to examine gene expression in donor and target cells
      separately. Our findings point to the conclusion that one or more soluble factors
      produced by the IPNV carrier culture induce the innate immune response within the
      target cells. This antiviral response is associated to the up-regulation of
      interferon (ifn) and mx gene expression in target EPC cells. To our knowledge
      this is the first article describing co-culture systems to study the interplay
      between virus-carrier cells and naive cells in fish.

PMID- 27693200
TI  - Proinflammatory cytokine and cytokine receptor gene expression kinetics following
      challenge with Flavobacterium psychrophilum in resistant and susceptible lines of
      rainbow trout (Oncorhynchus mykiss).
AB  - Flavobacterium psychrophilum (Fp) is the causative agent of bacterial cold water
      disease (BCWD) which causes appreciable economic losses in rainbow trout
      aquaculture. We previously reported development of a genetic line, designated ARS
      Fp-R that exhibits higher survival relative to a susceptible line, designated ARS
      Fp-S, following either laboratory or natural on-farm challenge. The objectives of
      this study were to determine the temporal kinetics of gene expression between
      experimentally-challenged ARS-Fp-R and ARS-Fp-S fish and the correlation between
      gene expression and pathogen load. We developed a GeXP multiplex RT-PCR assay to
      simultaneously examine expression of immune-relevant genes, concentrating on
      tumor necrosis factor and interleukin-1 ligand/receptor systems and acute phase
      response genes. Spleen tissue was sampled at 6 h, 24 h, 48 h and 144 h post
      challenge and pathogen load quantified by qPCR. Transcript abundance of cytokine
      genes tnfa1, tnfa2, tnfa3, il1b1, il1b2, il11a; acute phase response genes saa
      and drtp1; and putative cytokine receptors il1r1-like-b, il1r2, tnfrsf1a,
      tnfrsf9, tnfrsf1a-like-b increased following challenge while the transcript
      abundance of il1r-like-1 and tnfrsf1a-like-a decreased compared to PBS-injected
      line-matched control fish. Principal component analysis identified transcript
      levels of genes il1r-like-1 and tnfrsf1a-like-a as exhibiting differential
      expression between genetic lines. In summary, Fp i.p. injection challenge
      elicited a proinflammatory cytokine gene expression response in the spleen, with
      ARS-Fp-R line fish exhibiting modestly higher basal expression levels of several
      putative cytokine receptors. This study furthers the understanding of the immune
      response following Fp challenge and differences in gene expression associated
      with selective breeding for disease resistance.

PMID- 27693198
TI  - Effects of tissue susceptibility on brain temperature mapping.
AB  - A method for mapping of temperature over a large volume of the brain using
      volumetric proton MR spectroscopic imaging has been implemented and applied to
      150 normal subjects. Magnetic susceptibility-induced frequency shifts in gray-
      and white-matter regions were measured and included as a correction in the
      temperature mapping calculation. Additional sources of magnetic susceptibility
      variations of the individual metabolite resonance frequencies were also observed
      that reflect the cellular-level organization of the brain metabolites, with the
      most notable differences being attributed to changes of the N-Acetylaspartate
      resonance frequency that reflect the intra-axonal distribution and orientation of
      the white-matter tracts with respect to the applied magnetic field. These
      metabolite-specific susceptibility effects are also shown to change with age.
      Results indicate no change of apparent brain temperature with age from 18 to 84
      years old, with a trend for increased brain temperature throughout the cerebrum
      in females relative for males on the order of 0.1 degrees C; slightly increased
      temperatures in the left hemisphere relative to the right; and a lower
      temperature of 0.3 degrees C in the cerebellum relative to that of cerebral white
      matter. This study presents a novel acquisition method for noninvasive
      measurement of brain temperature that is of potential value for diagnostic
      purposes and treatment monitoring, while also demonstrating limitations of the
      measurement due to the confounding effects of tissue susceptibility variations.

PMID- 27693201
TI  - Dietary choline deficiency and excess induced intestinal inflammation and
      alteration of intestinal tight junction protein transcription potentially by
      modulating NF-kappaB, STAT and p38 MAPK signaling molecules in juvenile Jian
      carp.
AB  - This study investigated the effects of choline on intestinal mucosal immune and
      the possible mechanisms in fish by feeding juvenile Jian carp (Cyprinus carpio
      var. Jian) with graded levels of dietary choline (165-1820 mg/kg diet) for 65
      days. The results firstly showed that choline deficiency induced inflammatory
      infiltration in the proximal intestine (PI), mid intestine (MI) and distal
      intestine (DI) of fish. Meanwhile, compared with the optimal choline group,
      choline deficiency decreased the activities of lysozyme and acid phosphatase,
      contents of complement 3 and IgM in the intestine, downregulated the mRNA levels
      of antimicrobial peptides (liver-expressed antimicrobial peptide (LEAP) 2A and
      defensin-3 in the PI and MI, LEAP-2B and hepcidin in the PI, MI and DI), anti
      inflammatory cytokines (interleukin (IL) 10 and transforming growth factor beta2
      in the PI, MI and DI), and signaling molecule IkappaB in the PI, MI and DI; while
      upregulated the mRNA levels of pro-inflammatory cytokines (IL-6a and tumor
      necrosis factor alpha in the MI and DI, interferon gamma2b in the PI and MI, IL
      1beta and IL-6b in the PI, MI and DI), and signaling molecules (Toll-like
      receptor 4 in the MI, myeloid differentiation primary response 88 in the PI and
      MI, Janus kinase 3 and tyrosine kinase 2 in the MI and DI, nuclear factor kappa B
      (NF-kappaB), signal transducers and activators of transcription (STAT) 4 and
      STAT5 in the PI, MI and DI) of juvenile Jian carp, further indicating that
      choline deficiency caused inflammation and immunity depression in the intestine
      of fish. But choline deficiency decreased the PI IL-6a mRNA level, and increased
      the DI LEAP-2A and defensin-3 mRNA levels with unknown reasons. Furthermore,
      dietary choline deficiency downregulated mRNA levels of tight junction (TJ)
      proteins (claudin 3c in the PI and MI, claudin 7, claudin 11 and occludin in the
      PI, MI and DI) and signaling molecule mitogen-activated protein kinases p38 in
      the PI, MI and DI of juvenile Jian carp, whereas upregulated the mRNA levels of
      claudin 3b in the MI and DI, and claudin 3c in the DI. Moreover, the excessive
      choline exhibited negative effects on intestinal immunity and TJ proteins that
      were similar to the choline deficiency. In summary, dietary choline deficiency or
      excess caused the depression of intestinal mucosal immune by inducing
      inflammation and dysfunction of the intestinal physical barrier, and regulating
      related signaling molecules of fish.

PMID- 27693202
TI  - Effect of 4-nonylphenol on the immune response of the Pacific oyster Crassostrea
      gigas following bacterial infection with Vibrio campbellii.
AB  - The xenoestrogen 4-nonylphenol (NP) is a ubiquitous aquatic pollutant and has
      been shown to impair reproduction, development, growth and, more recently, immune
      function in marine invertebrates. We investigated the effects of short-term (7 d)
      exposure to low (2 MUg l-1) and high (100 MUg l-1) levels of NP on cellular and
      humoral elements of the innate immune response of Crassostrea gigas to a
      bacterial challenge. To this end, we measured 1) total hemocyte counts (THC), 2)
      relative transcript abundance of ten immune-related genes (defh1, defh2, bigdef1,
      bigdef2, bpi, lysozyme-1, galectin, C-type lectin 2, timp, and transglutaminase)
      in the hemocytes, gill and mantle, and 3) hemolymph plasma lysozyme activity,
      following experimental Vibrio campbellii infection. Both low and high levels of
      NP were found to repress a bacteria-induced increase in THC observed in the
      control oysters. While several genes were differentially expressed following
      bacterial introduction (bigdef2, bpi, lysozyme-1, timp, transglutaminase), only
      two genes (bpi in the hemocytes, transglutaminase in the mantle) exhibited a
      different bacteria-induced expression profile following NP exposure, relative to
      the control oysters. Independently of infection-status, exposure to NP also
      altered mRNA transcript abundance of several genes (bpi, galectin, C-type lectin
      2) in naive, saline-injected oysters. Finally, plasma lysozyme activity levels
      were significantly higher in low dose NP-treated oysters (both naive and bacteria
      challenged) relative to control oysters. Combined, these results suggest that
      exposure to ecologically-relevant (low) and extreme (high) levels of NP can alter
      both cellular and humoral elements of the innate immune response in C. gigas, an
      aquaculture species of global economic importance.

PMID- 27693203
TI  - Comparison of total costs between internal fixation and hemiarthroplasty for
      displaced femoral neck fractures.
AB  - BACKGROUND: There is very little information on the costs of different surgeries
      for displaced femoral neck fractures. This study aimed to compare the costs
      between internal fixation and hemiarthroplasty (HA) in the treatment of displaced
      femoral neck fracture. METHOD: A total of 142 patients aged 65 years or older who
      had been randomized into internal fixation group (n = 70) or HA group (n = 72)
      were followed for 2 years. Cost data was collected through hospitalization
      information, cost diary and telephone interview. Sensitivity analysis was
      performed for missing diaries. The total costs were collected and compared
      between the two groups. RESULTS: All diaries were completed by 69.7% of patients.
      The mean costs of primary treatment were significantly lower for internal
      fixation (CNY 21,631) compared with HA (CNY 51,641) (p < 0.001). The mean post
      discharge costs were similar for both procedures: CNY 37,377 for internal
      fixation and CNY 34,981 for HA (p = 0.640). The mean total costs for internal
      fixation were CNY 59,008, which was significantly lower than the mean total costs
      of CNY 86,622 for HA (p = 0.002). CONCLUSION: Although the post-discharge costs
      of internal fixation were slightly higher, the total costs were still lower than
      for HA due to great variance in costs of primary treatment. In China, internal
      fixation may be less costly than HA for displaced femoral neck fracture
      treatment.

PMID- 27693205
TI  - Perioperative Management of a Parturient After Atrial Switch Surgery for Dextro
      Transposition of the Great Vessels.

PMID- 27693207
TI  - Anesthetic Management of Transfemoral Transcatheter Aortic Valve Replacement
      (TAVR) in a Heart Transplant Recipient With Severely Depressed Left Ventricular
      Function and Renal Failure.

PMID- 27693204
TI  - Case Study: Johns Hopkins Community Health Partnership: A model for
      transformation.
AB  - To address the challenging health care needs of the population served by an urban
      academic medical center, we developed the Johns Hopkins Community Health
      Partnership (J-CHiP), a novel care coordination program that provides services in
      homes, community clinics, acute care hospitals, emergency departments, and
      skilled nursing facilities. This case study describes a comprehensive program
      that includes: a community-based intervention using multidisciplinary care teams
      that work closely with the patient's primary care provider; an acute care
      intervention bundle with collaborative team-based care; and a skilled nursing
      facility intervention emphasizing standardized transitions and targeted use of
      care pathways. The program seeks to improve clinical care within and across
      settings, to address the non-clinical determinants of health, and to ultimately
      improve healthcare utilization and costs. The case study introduces: a) main
      program features including rationale, goals, intervention design, and partnership
      development; b) illness burden and social barriers of the population contributing
      to care challenges and opportunities; and c) lessons learned with steps that have
      been taken to engage both patients and providers more actively in the care model.
      Urban health systems, including academic medical centers, must continue to
      innovate in care delivery through programs like J-CHiP to meet the needs of their
      patients and communities.

PMID- 27693208
TI  - Pulmonary Embolism: A Dynamic Situation.

PMID- 27693209
TI  - An Incidental Right Atrial Mass.

PMID- 27693210
TI  - A Rare Complication of Cardiopulmonary Resuscitation After Mitral Valve
      Replacement.

PMID- 27693206
TI  - Randomized Evidence for Reduction of Perioperative Mortality: An Updated
      Consensus Process.
AB  - OBJECTIVE: Of the 230 million patients undergoing major surgical procedures every
      year, more than 1 million will die within 30 days. Thus, any nonsurgical
      interventions that help reduce perioperative mortality might save thousands of
      lives. The authors have updated a previous consensus process to identify all the
      nonsurgical interventions, supported by randomized evidence, that may help reduce
      perioperative mortality. DESIGN AND SETTING: A web-based international consensus
      conference. PARTICIPANTS: The study comprised 500 clinicians from 61 countries.
      INTERVENTIONS: A systematic literature search was performed to identify published
      literature about nonsurgical interventions, supported by randomized evidence,
      showing a statistically significant impact on mortality. A consensus conference
      of experts discussed eligible papers. The interventions identified by the
      conference then were submitted to colleagues worldwide through a web-based
      survey. MEASUREMENTS AND MAIN RESULTS: The authors identified 11 interventions
      contributing to increased survival (perioperative hemodynamic optimization,
      neuraxial anesthesia, noninvasive ventilation, tranexamic acid, selective
      decontamination of the gastrointestinal tract, insulin for tight glycemic
      control, preoperative intra-aortic balloon pump, leuko-depleted red blood cells
      transfusion, levosimendan, volatile agents, and remote ischemic preconditioning)
      and 2 interventions showing increased mortality (beta-blocker therapy and
      aprotinin). Interventions then were voted on by participating clinicians.
      Percentages of agreement among clinicians in different countries differed
      significantly for 6 interventions, and a variable gap between evidence and
      clinical practice was noted. CONCLUSIONS: The authors identified 13 nonsurgical
      interventions that may decrease or increase perioperative mortality, with
      variable agreement by clinicians. Such interventions may be optimal candidates
      for investigation in high-quality trials and discussion in international
      guidelines to reduce perioperative mortality.

PMID- 27693211
TI  - Inhibition of SUMO-specific protease 1 induces apoptosis of astroglioma cells by
      regulating NF-kappaB/Akt pathways.
AB  - SUMO-specific protease 1 (SENP1) is an important regulation protease in the
      protein desumoylation, which was shown to have a prooncogenicrole in many types
      of cancer. However, the mechanism of action for SENP1 in astrocytoma is not yet
      clear. Astrocytoma is the most frequent one among various neurogliomas, of which
      a subtype known as glioblastoma multiforme (GBM) is the most malignant brain
      glioma and seriously influences the life quality of the patients. In this study,
      the expression of SENP1 was detected in 28 cases of various grades of astrocytoma
      and 6 cases of normal human tissues. The results showed that the expression of
      SENP1 was positively correlated with the malignant grades. Besides, the NF-kappaB
      and Akt signaling pathways in GBM tissues were activated. Cytological experiments
      indicated that knock-down of endogenous SENP1 promoted cell apoptosis. Further
      research confirmed that downexpression of SENP1 could inhibit the phosphorylation
      of IkappaBalpha and Akt, and also the expression of its downstream regulation
      factors Bcl-xL and cyclinD1. These results delineate a key role for SENP1 in
      astrocytoma development, suggesting it may be a potential new therapeutic target
      inastrocytoma.

PMID- 27693212
TI  - PRDM14 inhibits 293T cell proliferation by influencing the G1/S phase transition.
AB  - PRDM14 (PRDI-BF1 and RIZ domain-containing 14), a transcription factor, plays
      important roles in primordial germ cell specification and embryonic stem cell
      pluripotency, and supports the maintenance of self-renewal by promoting the
      expression of stem cell markers while also repressing the expression of
      differentiation factors. As a proto-oncogene, the ectopic expression of PRDM14
      can enhance breast cell growth and reduce breast cell sensitivity to
      chemotherapeutic drugs. Conversely, knockdown of PRDM14 expression induces
      apoptosis in breast cancer cells and restores their sensitivity to
      chemotherapeutic drugs. Here, we sought to identify the role of PRDM14 in 293T
      cells. PRDM14-infected 293T cells exhibited an abnormal morphology, and we found
      that ectopic expression of PRDM14 inhibits colony formation, cell proliferation
      and metastasis. In addition, our data indicated that PRDM14 influences the G1/S
      phase transition of 293T cells by inducing the expression of cell cycle
      regulators. In conclusion, these results showed that PRDM14 inhibits 293T cell
      proliferation by influencing the G1/S phase transition and impacts cell migration
      by regulating the level of MMP/TIMP expression, thus mediating extracellular
      matrix degradation.

PMID- 27693213
TI  - MMP 1 circulating levels and promoter polymorphism in risk prediction of coronary
      artery disease in asymptomatic first degree relatives.
AB  - Coronary artery disease (CAD) remains to be the prominent health problem in
      India, and its incidence is growing in developing countries as well. Matrix
      metalloproteinase 1 (MMP 1) is highly expressed in disruption-prone shoulder
      regions of the fibrous plaques. The present study aims to investigate association
      of MMP 1 gene polymorphisms (-1607 1G/2G) and serum circulating levels with CAD.
      The study includes 300 CAD patients, 100 FDRS, and 300 controls. ELISA and PCR
      RFLP were performed to determine MMP 1 serum levels and genotypes respectively.
      MMP1 levels were high in CAD patients, followed by FDRS compared to controls
      (2.15+/-1.2ng/ml; 1.46+/-1.04ng/ml and 0.96+/-0.53ng/ml) respectively. ROC
      analysis showed the AUC at 95% CI of serum MMP-1 to be 0.83 and 0.73-0.94,
      respectively. The optimal cut-off point (sensitivity; specificity) of serum MMP 1
      was >1.5ng/ml (0.74; 0.90). The 2G/2G genotype was associated with high MMP 1
      circulating levels in CAD patients, and a similar trend was observed in FDRS and
      controls. The pre-mRNA secondary structure of the 2G allele is much more stable
      than 1G allele. Our results suggest MMP 1 serum levels and polymorphism as
      potential independent prognostic markers for future cardiovascular events. These
      may also help to stratify CAD patients and to identify susceptibility for CAD in
      asymptomatic healthy FDRS.

PMID- 27693214
TI  - Identification of the impact on T- and B- cell epitopes of human papillomavirus
      type-16 E6 and E7 variant in Southwest China.
AB  - Cervical cancers almost are infected by human papillmavirus (HPV), encoding E6
      and E7 oncoproteins which are regard as ideal targets on the mechanism of this
      disease and development of vaccines. HLA (human leukocyte antigen) participates
      in the local immune response to prevent tumor invasion and progression. But due
      to highly polymorphism of HLA, prediction shows its importance in this study.
      More effective immunoinformatics was used for predicting epitopes from HPV-16 E6
      and E7, including T- and B-cell epitopes. Eight substitutions are detected.
      Specifically speaking, for HLA-I, HLA-A*33:03 (26), HLA-B*13:01 (14), HLA-C*03:02
      (5) for E6 and HLA-A*02:01 (6), HLA-B*40:01 (5), HLA-C*03:04 (4) for E7 are most
      frequency. Epitope 41-48EVYDFAFR for HLA-A*33:03 (0.1) for E6 has best binding
      affinity, as well as HLA*02:01 and HLA-B*40:01 (0.2) for E7. The mutations of
      D25E and L83V of E6 and N29S of E7 produce new epitopes, and the percentile
      values change with them. For HLA-II, seventeen epitopes in the reference at
      percentile value from 0.22 to 4.76, while in variant from 0.22 to 4.96. For the B
      cell epitopes, three most potent epitopes for E6 were listed, and N29S lead the
      growth of score from 0.81 to 0.83. In summary, E640-55REVYDFAFRDLCIVYR and E711
      22YMLDLQPETTDL are the important regions, containing the majority of predicted
      epitopes. E6 72-83 for HLA-A*02:01 and E6 74-84 for HLA-B*15:02 maybe are the new
      direct for therapeutic vaccine aimed at L83V variants. HLA-DRB1*15:02 is better
      binder with T cell in our HLA class II. It is a systematic, detail recognition
      for T- and B-cell epitopes of HPV-16 E6 and E7 from Southwest China, which may be
      helpful to design vaccines specifically for women in Southwest China and testing
      methods specifically for this region. The results of our study may contribute to
      future researches on vaccines improvement, or screening methods for a particular
      population.

PMID- 27693215
TI  - Primary open angle glaucoma in type 2 diabetes: Implications of the IL-10/STAT3
      mediated anti-inflammatory response?

PMID- 27693216
TI  - Tianeptine, antidepressant with positive benefit/risk.

PMID- 27693217
TI  - The relationships between deformation mechanisms and mechanical properties of
      additively manufactured porous biomaterials.
AB  - Modulating deformation mechanism through manipulating morphological parameters of
      scaffold internal pore architecture provides potential to tailor the overall
      mechanical properties under physiological loadings. Whereas cells sense local
      strains, cell differentiation is also impressed by the elastic deformations. In
      this paper, structure-property relations were developed for Ti6-Al-4V scaffolds
      designed based on triply periodic minimal surfaces. 10mm cubic scaffolds composed
      of 5*5*5 unit cells formed of F-RD (bending dominated) and I-WP (stretching
      dominated) architectures were additively manufactured at different volume
      fractions and subjected to compressive tests. The first stages of deformation for
      stretching dominated structure, was accompanied by bilateral layer-by-layer
      failure of unit cells owing to the buckling of micro-struts, while for bending
      dominated structure, namely F-RD, global shearing bands appeared since the
      shearing failure of struts in the internal architecture. Promoted mechanical
      properties were found for stretching dominated structure since the global
      orientation of struts were parallel to loading direction while inclination of
      struts diminished specific properties for bending dominated structure. Moreover,
      elastic-plastic deformation was computationally studied by applying Johnson-Cook
      damage model to the voxel-based models in FE analysis. Scaling analysis was
      performed for mechanical properties with respect to the relative density thereby
      failure mechanism was correlated to the constants of power law describing
      mechanical properties.

PMID- 27693218
TI  - MiR-383 inhibits proliferation, migration and angiogenesis of glioma-exposed
      endothelial cells in vitro via VEGF-mediated FAK and Src signaling pathways.
AB  - Malignant glioma is undoubtedly the most vascularized tumor of central nervous
      system. Angiogenesis, playing a predominant role in tumor progression, is widely
      considered as a key point of tumor treatment. The aim of this study was to
      investigate the potential effects of miR-383 on proliferation, migration, tube
      formation and angiogenesis of glioma-exposed endothelial cells (GECs) in vitro
      and to further elucidate its possible molecular mechanisms. The expression of miR
      383 in GECs was significantly downregulated compared with that in normal
      endothelial cells (ECs). Overexpression of miR-383 dramatically inhibited the
      proliferation, migration, tube formation and spheroid-based angiogenesis of GECs
      in vitro. Dual-luciferase reporter results demonstrated vascular endothelial
      growth factor (VEGF) is a target gene of miR-383. Furthermore, overexpression or
      silencing of either miR-383 or VEGF was performed simultaneously to further
      clarify that miR-383 inhibited proliferation, migration and angiogenesis of GECs
      in vitro by targeting VEGF. Finally, VEGF/VEGFR2-mediated FAK and Src signaling
      pathways might contribute to anti-angiogenesis of GECs. In conclusion, our
      present study indicated that miR-383 inhibits proliferation, migration and
      angiogenesis of GECs in vitro via VEGF/VEGFR2-mediated FAK and Src signaling
      pathways, which would draw growing attention to miR-383c as a potential
      therapeutical target of glioma.

PMID- 27693219
TI  - FhCaBP1 (FH22): A Fasciola hepatica calcium-binding protein with EF-hand and
      dynein light chain domains.
AB  - FH22 has been previously identified as a calcium-binding protein from the common
      liver fluke, Fasciola hepatica. It is part of a family of at least four proteins
      in this organism which combine an EF-hand containing N-terminal domain with a C
      terminal dynein light chain-like domain. Here we report further biochemical
      properties of FH22, which we propose should be renamed FhCaBP1 for consistency
      with other family members. Molecular modelling predicted that the two domains are
      linked by a flexible region and that the second EF-hand in the N-terminal domain
      is most likely the calcium ion binding site. Native gel electrophoresis
      demonstrated that the protein binds both calcium and manganese ions, but not
      cadmium, magnesium, strontium, barium, cobalt, copper(II), iron (II), nickel,
      zinc, lead or potassium ions. Calcium ion binding alters the conformation of the
      protein and increases its stability towards thermal denaturation. FhCaBP1 is a
      dimer in solution and calcium ions have no detectable effect on the protein's
      ability to dimerise. FhCaBP1 binds to the calmodulin antagonists trifluoperazine
      and chlorpromazine. Overall, the FhCaBP1's biochemical properties are most
      similar to FhCaBP2 a fact consistent with the close sequence and predicted
      structural similarity between the two proteins.

PMID- 27693220
TI  - Screening and characterization of apical membrane antigen 1 interacting proteins
      in Eimeria tenella.
AB  - Avian coccidiosis is a widespread and economically significant disease of
      poultry. It is an enteric disease caused by several protozoan Eimeria species.
      Eimeria belongs to the phylum Apicomplexa, which exhibits an unusual mechanism of
      host cell invasion. During invasion of host cells, the protein apical membrane
      antigen 1 (AMA1) is essential for invasion of Toxoplasma gondii and Plasmodium.
      Contrary to the roles of AMA1 during host cell invasion in T. gondii and
      Plasmodium, the precise functions of Eimeria AMA1 (EtAMA1) are unclear. In order
      to study the functions of EtAMA1, a yeast two-hybrid cDNA library was constructed
      from E. tenella sporozoites. The EtAMA1 ectodomain was cloned into the pGBKT7
      vector to construct the bait plasmid pGBKT7- EtAMA1. Autoactivation and toxicity
      of the bait protein in yeast cells were tested by comparison with the pGBKT7
      empty vector. Expression of the bait protein was detected by western blots. The
      bait plasmid pGBKT7-EtAMA1 was used to screen yeast two-hybrid cDNA library from
      E. tenella sporozoites. After multiple screenings with high-screening-rate medium
      and exclusion of false-positive plasmids, positive preys were sequenced and
      analyzed using BLAST. We obtained 14 putative EtAMA1-interacting proteins
      including E. tenella acidic microneme protein2 (EtMIC2), E. tenella putative
      cystathionine beta-synthase, E. tenella Eimeria-specific protein, four E. tenella
      conserved hypothetical proteins (one in the serine/threonine protein kinase
      family) and seven unknown proteins. Gene Ontology analysis indicated that two
      known proteins were associated with metabolic process, pyridoxal phosphate
      binding and protein phosphorylation. Functional analysis indicated EtMIC2 was
      implicated in parasite motility, migration, recognition and invasion of host
      cells. The data suggested that EtAMA1 may be important during host cell invasion,
      but also involved in other biological processes.

PMID- 27693221
TI  - Trichomonas gallinae: Prevalence and molecular characterization from pigeons in
      Minoufiya governorate, Egypt.
AB  - Trichomonas gallinae infects the upper digestive tract of pigeons. It is
      transmitted from mother to young squabs by feeding crop milk. Generally,
      infection resulted in severe mortalities in young birds. In this study, we
      examined 3315 pigeons of different ages from the Minoufiya governorate for the
      clinical infection by T. gallinae. The infection was confirmed in infected birds
      by microscopical examination of oral swabs, histopathological examination, and
      PCR of the ITS1/5.8S/ITS2 gene. The prevalence was 63 (1.9%). The parasite was
      found in 35 (2.04%) from Ashmoun, 15 (1.66%) from Minoof, 8 (1.6%) from Quesna,
      and 5 (2.5%) from El-Shohada birds. The infection was mainly detected in squabs
      60 (1.8%). The sequence of T. gallinae ITS1/5.8S/ITS2 gene from Egypt has high
      nucleotide sequence identity (up to100%) to T. gallinae from pigeon of USA,
      Austria, Canada, and Spain. The sequence belongs to genotype B of T. gallinae.
      Histopathological examination presented the parasites in crop, liver, larynx, and
      trachea as poorly eosinophilic bodies with severe inflammatory cell infiltration.
      This is the first study to present the prevalence and genotype of T. gallinae
      from Minoufiya governorate, Egypt.

PMID- 27693222
TI  - Hepatic injury associated with Trypanosoma cruzi infection is attenuated by
      treatment with 15-deoxy-Delta12,14 prostaglandin J2.
AB  - Trypanosoma cruzi, the etiological agent of Chagas' disease, causes an intense
      inflammatory response in several tissues, including the liver. Since this organ
      is central to metabolism, its infection may be reflected in the outcome of the
      disease. 15-deoxy-Delta12,14 prostaglandin J2 (15dPGJ2), a natural agonist of
      peroxisome-proliferator activated receptor (PPAR) gamma, has been shown to exert
      anti-inflammatory effects in the heart upon T. cruzi infection. However, its role
      in the restoration of liver function and reduction of liver inflammation has not
      been studied yet. BALB/c mice were infected with T. cruzi. The effects of in vivo
      treatment with 15dPGJ2 on liver inflammation and fibrosis, as well as on the
      GOT/GPT ratio were studied and the role of NF-kappaB pathway on 15dPGJ2-mediated
      effects was analysed. 15dPGJ2 reduced liver inflammatory infiltrates,
      proinflammatory enzymes and cytokines expression, restored the De Ritis ratio
      values to normal, reduced the deposits of interstitial and perisinusoidal
      collagen, reduced the expression of the pro-fibrotic cytokines and inhibited the
      translocation of the p65 NF-kappaB subunit to the nucleus. Thus, we showed that
      15dPGJ2 is able to significantly reduce the inflammatory response and fibrosis
      and reduced enzyme markers of liver damage in mice infected with T. cruzi.

PMID- 27693223
TI  - Experimental infection of calves with Haemonchus placei or Haemonchus contortus:
      Assessment of clinical, hematological and biochemical parameters and
      histopathological characteristics of abomasums.
AB  - The present study had the primary objective of evaluating clinical, hematological
      and biochemical parameters, as well as observing anatomical and histopathological
      characteristics of abomasums, from calves prime-infected with Haemonchus
      contortus or H. placei. Ten male Holstein newborns were subdivided in three
      groups (GI placebo; GII infected with H. contortus; GIII inoculated with H.
      placei). Eye mucosa staining was evaluated. Hematological and biochemical tests
      were performed on animals. The euthanasia of all ten experimental calves was
      performed on the 42nd day post-inoculation. Fragments were collected from each of
      all 10 abomasums for histopathological analysis. Discrete submandibular edema was
      diagnosed in animals from both infected groups (H. contortus or H. placei).
      However, there were no significant changes (P > 0.05) in the color of the ocular
      mucosa of calves from all three experimental groups across the entire
      experimental period. Hematological and biochemical changes diagnosed on animals
      could not be linked to infections by species of Haemonchus spp. Regarding
      histopathological exams, it was possible to diagnose hypertrophy, hyperplasia,
      binucleated cells, inflammatory infiltrate, multifocal hemorrhage and edema in
      abomasums from calves of both groups infected with H. placei and H. contortus. It
      can, thus, be concluded that not only are calves susceptible to infections by
      both Haemonchus species, but they can also present clinical changes and similar
      anatomic histopathological lesions independent of being infected by Haemonchus
      placei or Haemonchus contortus. These results reflect a negative effect on
      helminth control by mixed grazing between sheep and cattle, especially when using
      calves.

PMID- 27693224
TI  - Standardizing dose prescriptions: An ASTRO white paper.
AB  - This white paper recommends the standardization (content and presentation order)
      of several "key components" of the radiation therapy prescription to facilitate
      accurate communication between radiation therapy care providers. The rationale,
      other similar efforts, and detailed considerations are described. In brief, the
      Task Force recommends that the prescription's "elements" include: treatment site,
      method of delivery, dose per fraction, total number of fractions, total dose (eg,
      right breast, tangent photons, 267 cGy * 16 = 4272 cGy). A similar formalism is
      recommended for brachytherapy (eg, cervix, Ir-192 brachytherapy, 600cGy * 5 =
      3000 cGy) and other modalities. The white paper also considers future directions
      for other items such as the simulation order, treatment planning objectives,
      prescription point or volume, treatment schedule, localization imaging,
      laboratory monitoring, concurrent chemotherapy, patient instructions for
      treatment, etc. The intent of this white paper is to facilitate accurate
      communication among providers to support safe practice as well as to guide
      vendors in product development that is consistent with this standard
      prescription.

PMID- 27693225
TI  - Salvage external beam radiotherapy for locally recurrent prostate cancer after
      definitive brachytherapy.
AB  - PURPOSE: Patients with locally recurrent prostate cancer after definitive
      prostate brachytherapy have few evidence-based salvage options. We evaluate the
      efficacy and treatment-related side-effects of salvage external-beam radiotherapy
      (EBRT) after definitive prostate brachytherapy (PBT). METHODS AND MATERIALS:
      Eleven patients previously treated with definitive PBT and with biopsy-proven
      local-only recurrence received salvage reirradiation with EBRT. Genitourinary
      (GU) function was assessed with International Prostate Symptom Scores. Treatment
      related toxicities were graded using CTCAE v 4.03. RESULTS: Median follow-up was
      26.5 months (range, 1-53.6 months); median age at EBRT salvage was 67 years
      (range, 61-81 years). Salvage EBRT included the whole pelvis in 8 patients. Two
      patients were treated with 3D-CRT; 9 underwent IMRT. Five patients (45%) received
      androgen deprivation therapy concurrent with salvage EBRT as part of long- or
      short-course hormone therapy. The median prostate dose was 70.2 Gy (range, 64.8
      75.6 Gy). Actuarial 3-year overall and biochemical failure-free survival were 77%
      and 69%, respectively. Five patients (45%) had worsening GU symptoms, and 9 (82%)
      experienced a decline in erectile function. One patient experienced acute grade 2
      GU toxicity. Four patients (36%) experienced late grade >=2 GI/GU toxicities,
      including 2 who experienced grade 3 toxicities (rectourethral
      fistula/incontinence, bladder outlet obstruction). No grade 4/5 toxicities were
      noted. CONCLUSIONS: Our data suggest that salvage EBRT can provide similar
      disease control and treatment-related toxicity to more established salvage
      therapies. This approach warrants further investigation on a larger scale.

PMID- 27693226
TI  - Does intensity or youth affect the neurobiological effect of exercise on major
      depressive disorder?
AB  - The purpose of this commentary is to discuss the different neurobiological
      effects of exercise on major depressive disorder (MDD) in children and
      adolescents and to provide additional explanations to this well written
      systematic review. This commentary highlights the effects of exercise on the
      hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in MDD. We
      address the questions of whether age and different exercise intensities may
      provide additional information on the neurobiological effects of acute or chronic
      exercise on MDD. Previous findings clearly suggest that the etiology of MDD is
      complex and multifaceted, involving numerous neurobiological systems, which are
      additionally influenced by these two factors.

PMID- 27693227
TI  - Appetitive Pavlovian-instrumental Transfer: A review.
AB  - Reward-related cues are an important part of our daily life as they often
      influence and guide our actions. This paper reviews one of the experimental
      paradigms used to study the effects of cues, the Pavlovian to Instrumental
      Transfer paradigm. In this paradigm, cues associated with rewards through
      Pavlovian conditioning alter motivation and choice of instrumental actions. The
      first transfer experiments date back to the 1940s, but only in the last decade
      has it been fully recognised that there are two types of transfer, specific and
      general. This paper presents a systematic review of both the neural substrates
      and the behavioral factors affecting both types of transfer. It also examines the
      recent application of the paradigm to study the effect of cues on human
      participants, both in normal and pathological conditions, and the interactions of
      transfer with drugs of abuse. Finally, the paper analyses the theoretical aspects
      of transfer to build an overall picture of the phenomenon, from early theories to
      recent hierarchical accounts.

PMID- 27693229
TI  - The research domain criteria framework: The case for anterior cingulate cortex.
AB  - The United States National Institute of Mental Health has recently promoted the
      Research Domain Criteria framework, which emphasizes the study of neurocognitive
      constructs that cut across different disorders. These constructs are said to
      express dimensionally across the population, giving rise to psychopathologies
      only in the extreme cases where that expression is maladaptive. Inspired by the
      RDoC framework, we propose that recent insights into the function of anterior
      cingulate cortex (ACC), a brain area said to be responsible for selecting and
      motivating extended behaviors, may elucidate the etiology of a diverse array of
      mental disorders. We argue that ACC function contributes to individual
      differences in personality traits related to reward sensitivity and persistence,
      and propose that the maladaptive expression of these traits contributes to
      multiple mental and neurological disorders. Our discussion is organized around a
      computational framework that relates the reward processing and control functions
      of ACC, as revealed by two electrophysiological phenomena called the reward
      positivity and frontal midline theta oscillations, to a distributed neural system
      underlying cognitive control.

PMID- 27693228
TI  - A systematic review of temporal discounting in eating disorders and obesity:
      Behavioural and neuroimaging findings.
AB  - OBJECTIVE: Eating Disorders (ED) and obesity are suggested to involve a spectrum
      of self-regulatory control difficulties. Temporal discounting (TD) tasks have
      been used to explore this idea. This systematic review examines behavioural and
      neuroimaging TD data in ED and obesity. METHOD: Using PRISMA guidelines, we
      reviewed relevant articles in MEDLINE, PsycINFO and Embase from inception until
      17th August 2016. Studies that reported behavioural differences in TD and/or TD
      neuroimaging data in ED/obesity were included. RESULTS: Thirty-one studies were
      included. Limited data suggest that BN, BED and obesity are associated with
      increased TD, whilst data in AN are mixed. Aberrant neural activity in
      frontostriatal circuitry is implicated. TD tasks vary widely and TD in ED/obesity
      may vary according to factors such as illness stage. CONCLUSION: Our findings
      suggest altered self-regulatory control in ED and obesity. TD tasks are
      heterogeneous, limiting generalisability of findings. Research into whether TD is
      multidimensional, along with transdiagnostic neuroimaging research is needed.
      Assessment of TD may be useful in psychoeducation, outcome prediction and
      treatment of ED/obesity.

PMID- 27693230
TI  - Importance of astrocytes for potassium ion (K+) homeostasis in brain and glial
      effects of K+ and its transporters on learning.
AB  - Initial clearance of extracellular K+ ([K+]o) following neuronal excitation
      occurs by astrocytic uptake, because elevated [K+]o activates astrocytic but not
      neuronal Na+,K+-ATPases. Subsequently, astrocytic K+ is re-released via Kir4.1
      channels after distribution in the astrocytic functional syncytium via gap
      junctions. The dispersal ensures widespread release, preventing renewed [K+]o
      increase and allowing neuronal Na+,K+-ATPase-mediated re-uptake. Na+,K+-ATPase
      operation creates extracellular hypertonicity and cell shrinkage which is
      reversed by the astrocytic cotransporter NKCC1. Inhibition of Kir channels by
      activation of specific PKC isotypes may decrease syncytial distribution and
      enable physiologically occurring [K+]o increases to open L-channels for Ca2+,
      activating [K+]o-stimulated gliotransmitter release and regulating gap junctions.
      Learning is impaired when [K+]o is decreased to levels mainly affecting
      astrocytic membrane potential or Na+,K+-ATPase or by abnormalities in its alpha2
      subunit. It is enhanced by NKCC1-mediated ion and water uptake during the
      undershoot, reversing neuronal inactivity, but impaired in migraine with aura in
      which [K+]o is highly increased. Vasopressin augments NKCC1 effects and
      facilitates learning. Enhanced myelination, facilitated by astrocytic
      oligodendrocytic gap junctions also promotes learning.

PMID- 27693231
TI  - Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis
      Imperfecta.
AB  - Amelogenesis is the process of dental enamel formation, leading to the deposition
      of the hardest tissue in the human body. This process requires the intricate
      regulation of ion transport and controlled changes to the pH of the developing
      enamel matrix. The means by which the enamel organ regulates pH during
      amelogenesis is largely unknown. We identified rare homozygous variants in GPR68
      in three families with amelogenesis imperfecta, a genetically and phenotypically
      heterogeneous group of inherited conditions associated with abnormal enamel
      formation. Each of these homozygous variants (a large in-frame deletion, a
      frameshift deletion, and a missense variant) were predicted to result in loss of
      function. GPR68 encodes a proton-sensing G-protein-coupled receptor with
      sensitivity in the pH range that occurs in the developing enamel matrix during
      amelogenesis. Immunohistochemistry of rat mandibles confirmed localization of
      GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role
      for GPR68 as a proton sensor that is required for proper enamel formation.

PMID- 27693234
TI  - Observations on different resin strategies for affinity purification mass
      spectrometry of a tagged protein.
AB  - Co-affinity purification mass spectrometry (CoAP-MS) is a highly effective method
      for identifying protein complexes from a biological sample and inferring
      important interactions, but the impact of the solid support is usually not
      considered in design of such experiments. Affinity purification (AP) experiments
      typically utilize a bait protein expressing a peptide tag such as FLAG, c-Myc, HA
      or V5 and high affinity antibodies to these peptide sequences to facilitate
      isolation of a bait protein to co-purify interacting proteins. We observed
      significant variability for isolation of tagged bait proteins between Protein A/G
      Agarose, Protein G Dynabeads, and AminoLink resins. While previous research
      identified the importance of tag sequence and their location, crosslinking
      procedures, reagents, dilution, and detergent concentrations, the effect of the
      resin itself has not been considered. Our data suggest the type of solid support
      is important and, under the conditions of our experiments, AminoLink resin
      provided a more robust solid-support platform for AP-MS.

PMID- 27693235
TI  - The defender against apoptotic cell death 1 gene is required for tissue growth
      and efficient N-glycosylation in Drosophila melanogaster.
AB  - How organ growth is regulated in multicellular organisms is a long-standing
      question in developmental biology. It is known that coordination of cell
      apoptosis and proliferation is critical in cell number and overall organ size
      control, while how these processes are regulated is still under investigation. In
      this study, we found that functional loss of a gene in Drosophila, named
      Drosophila defender against apoptotic cell death 1 (dDad1), leads to a reduction
      of tissue growth due to increased apoptosis and lack of cell proliferation. The
      dDad1 protein, an orthologue of mammalian Dad1, was found to be crucial for
      protein N-glycosylation in developing tissues. Our study demonstrated that loss
      of dDad1 function activates JNK signaling and blocking the JNK pathway in dDad1
      knock-down tissues suppresses cell apoptosis and partially restores organ size.
      In addition, reduction of dDad1 triggers ER stress and activates unfolded protein
      response (UPR) signaling, prior to the activation of JNK signaling. Furthermore,
      Perk-Atf4 signaling, one branch of UPR pathways, appears to play a dual role in
      inducing cell apoptosis and mediating compensatory cell proliferation in this
      dDad1 knock-down model.

PMID- 27693233
TI  - Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset
      Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number.
AB  - Mutations in SLC25A4 encoding the mitochondrial ADP/ATP carrier AAC1 are well
      recognized causes of mitochondrial disease. Several heterozygous SLC25A4
      mutations cause adult-onset autosomal-dominant progressive external
      ophthalmoplegia associated with multiple mitochondrial DNA deletions, whereas
      recessive SLC25A4 mutations cause childhood-onset mitochondrial myopathy and
      cardiomyopathy. Here, we describe the identification by whole-exome sequencing of
      seven probands harboring dominant, de novo SLC25A4 mutations. All affected
      individuals presented at birth, were ventilator dependent and, where tested,
      revealed severe combined mitochondrial respiratory chain deficiencies associated
      with a marked loss of mitochondrial DNA copy number in skeletal muscle.
      Strikingly, an identical c.239G>A (p.Arg80His) mutation was present in four of
      the seven subjects, and the other three case subjects harbored the same c.703C>G
      (p.Arg235Gly) mutation. Analysis of skeletal muscle revealed a marked decrease of
      AAC1 protein levels and loss of respiratory chain complexes containing
      mitochondrial DNA-encoded subunits. We show that both recombinant AAC1 mutant
      proteins are severely impaired in ADP/ATP transport, affecting most likely the
      substrate binding and mechanics of the carrier, respectively. This highly reduced
      capacity for transport probably affects mitochondrial DNA maintenance and in turn
      respiration, causing a severe energy crisis. The confirmation of the
      pathogenicity of these de novo SLC25A4 mutations highlights a third distinct
      clinical phenotype associated with mutation of this gene and demonstrates that
      early-onset mitochondrial disease can be caused by recurrent de novo mutations,
      which has significant implications for the application and analysis of whole
      exome sequencing data in mitochondrial disease.

PMID- 27693236
TI  - Bovine epididymal spermatozoa: Resistance to cryopreservation and binding ability
      to oviductal cells.
AB  - In this study we examined quality, longevity and ability of epididymal sperm (EP)
      to bind to oviduct explants (OE) after cooling and cryopreservation. Ejaculated
      (EJ) and EP sperm from seven bulls were evaluated before, during and after
      cryopreservation for total (TM), progressive motility (PM), sperm morphology,
      plasma membrane integrity (PMI) and acrosome integrity (ACI). For longevity,
      cryopreserved EP, EJ and a third group of cells in which EP spermatozoa were
      incubated with seminal plasm (SP) for 10 min after thawing (EPP group), were
      compared, and the groups were analyzed at 0, 3, 6, and 24 h for all parameters.
      Sperm from each group were co-incubated with OE for 30 min, 6 h, and 24 h for
      binding evaluation. Data were analyzed by the generalized linear models SAS 9.1
      (P < 0.05). After cooling, EP displayed higher TM, higher PMI, and higher ACI (P
      < 0.05) than EJ. No differences were noted in the percentage of spermatozoa with
      PMI and AI between EJ and EP for fresh, cooled or cryopreserved sperm. However, a
      reduction in motility occurred in the EJ sperm after cooling, while in EP group
      such reduction occurred only after cryopreservation. At 6 h of incubation EP and
      EPP had higher PMI and ACI than EJ (P < 0.05). The number of spermatozoa bound to
      OE was similar P > 0.05) for all groups either at 30 min or 24 h. We conclude
      that EP are more resistant to cooling than EJ, and can bind to OE similarly to
      EJ.

PMID- 27693237
TI  - Transcranial Direct Current Stimulation in Mesial Temporal Lobe Epilepsy and
      Hippocampal Sclerosis.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) has been evaluated in
      medication refractory epilepsy patients. The results have been inconclusive and
      protocols have varied between studies. OBJECTIVE: To evaluate the safety and
      efficacy of two protocols of tDCS in adult patients with mesial temporal lobe
      epilepsy and hippocampal sclerosis (MTLE-HS). METHODS: This is a randomized
      placebo-controlled, double-blinded clinical trial, with 3 arms, 3 sessions, 5
      sessions and placebo stimulation. Frequency of seizures (SZs), interictal
      epileptiform discharges (IEDs) and adverse effects (AEs) were registered before
      and after treatment, and at 30 and 60 days follow-up. Descriptive statistics, k
      related samples, Friedman's test, and relative risk (RR) estimation were used for
      analysis. RESULTS: We included twenty-eight subjects (3d n = 12, 5d n = 8,
      placebo n = 8), 16/28 (57%) men, age 37.8(+/-10.9) years old. There was a
      significant reduction of the frequency of SZs at one (p = 0.001) and two (p =
      0.0001) months following cathodal tDCS compared to baseline in the 3 arms (p =
      0.0001). The mean reduction of SZ frequency at two months in both active groups
      was significantly higher than placebo (-48% vs. -6.25%, p < 0.008). At 3 days (
      43.4% vs. -6.25%, p < 0.007) and 5 days (-54.6% vs. -6.25%, p < 0.010) individual
      groups showed a greater reduction of SZs. A significant IED reduction effect was
      found between baseline and immediately after interventions (p = 0.041) in all
      groups. Side effects were minor. CONCLUSIONS: Cathodal tDCS technique of 3 and 5
      sessions decreased the frequency of SZs and IEDs (between baseline and
      immediately post-tDCS) in adult patients with MTLE-HS compared to placebo tDCS.

PMID- 27693239
TI  - Fast-track approval of medicines in Australia.

PMID- 27693238
TI  - Synthesis and characterization of nanosilver-silicone hydrogel composites for
      inhibition of bacteria growth.
AB  - PURPOSE: Nanosilver-silicone hydrogel (NAgSiH) composites for contact lenses were
      synthesized to asses the antimicrobial effects. METHODS: Silicone hydrogel (SiH)
      films were synthesized followed by impregnation in silver nitrate solutions (10,
      20, 30, 40, 60, 80ppm) and in-situ chemical reduction of silver ions using sodium
      borohydride (NaBH4). The silver nano particles (AgNPS) were identified by UV-vis
      absorption spectroscopy, Energy-dispersive X-ray spectroscopy (EDX) mapping and
      EDX spectrum. Physico-mechanical and chemical properties of NAgSIH films were
      studied. The antimicrobial effect of the hydrogels against Escherichia coli,
      Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus was
      evaluated. The numbers of viable bacterial cells on NAgSiH surface or in solution
      compared to control SiH were examined. RESULTS: The NAgSiH films were
      successfully synthesized. FTIR results indicated that AgNPS had no effect on the
      bulk structure of the prepared SiH films. From TGA analysis, NAgSiH(R80) and
      SiH(R0) films had the same maximum decomposition temperature (404 degrees C). UV
      vis absorption spectroscopy and EDX mapping and spectrum emphasized that AgNPS
      were in spherical shape. The maximum absorption wavelength of NAgSiH films were
      around 400nm. The light transmittance decreased as the concentration of AgNPS
      increased, but still greater than 90% at wavelength around 555nm. The Young's
      modulus increased gradually from 1.06MPa of SiH(R0) to highest value 1.38MPa of
      NAgSiH(R80). AgNPS incorporated into SiH films reduced the bacterial cell growth
      and prevented colonization. Groups NAgSiH(R60,R80) demonstrated an excellent
      reduction in bacterial viability in solution and on the SiH surface. CONCLUSIONS:
      NAgSiH composites were successfully synthesized and possessed an excellent
      antimicrobial effects.

PMID- 27693232
TI  - De Novo Truncating Variants in ASXL2 Are Associated with a Unique and
      Recognizable Clinical Phenotype.
AB  - The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during
      embryogenesis and encode proteins involved in epigenetic regulation and assembly
      of transcription factors to specific genomic loci. Germline de novo truncating
      variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring
      Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of
      severe intellectual disability and dysmorphic features. ASXL2 has not yet been
      associated with a human Mendelian disorder. In this study, we performed whole
      exome sequencing in six unrelated probands with developmental delay,
      macrocephaly, and dysmorphic features. All six had de novo truncating variants in
      ASXL2. A careful review enabled the recognition of a specific phenotype
      consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a
      glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and
      developmental disabilities. Although overlapping features with Bohring-Opitz and
      Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated
      condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of
      growth retardation, and more variability in the degree of intellectual
      disabilities. We were also able to demonstrate with mRNA studies that these
      variants are likely to exert a dominant-negative effect, given that both alleles
      are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated
      decay. In conclusion, de novo truncating variants in ASXL2 underlie a
      neurodevelopmental syndrome with a clinically recognizable phenotype. This report
      expands the germline disorders that are linked to the ASXL genes.

PMID- 27693241
TI  - The role of the anti-ageing protein Klotho in vascular physiology and
      pathophysiology.
AB  - Klotho is an anti-ageing protein that functions in many pathways that govern
      ageing, like regulation of phosphate homeostasis, insulin signaling, and Wnt
      signaling. Klotho expression levels and levels in blood decline during ageing.
      The vascular phenotype of Klotho deficiency features medial calcification, intima
      hyperplasia, endothelial dysfunction, arterial stiffening, hypertension, and
      impaired angiogenesis and vasculogenesis, with characteristics similar to aged
      human arteries. Klotho-deficient phenotypes can be prevented and rescued by
      Klotho gene expression or protein supplementation. High phosphate levels are
      likely to be directly pathogenic and are a prerequisite for medial calcification,
      but more important determinants are pathways that regulate cellular senescence,
      suggesting that deficiency of Klotho renders cells susceptible to phosphate
      toxicity. Overexpression of Klotho is shown to ameliorate medial calcification,
      endothelial dysfunction, and hypertension. Endogenous vascular Klotho expression
      is a controversial subject and, currently, no compelling evidence exists that
      supports the existence of vascular membrane-bound Klotho expression, as expressed
      in kidney. In vitro, Klotho has been shown to decrease oxidative stress and
      apoptosis in both SMCs and ECs, to reduce SMC calcification, to maintain the
      contractile SMC phenotype, and to prevent MU-calpain overactivation in ECs.
      Klotho has many protective effects with regard to the vasculature and constitutes
      a very promising therapeutic target. The purpose of this review is to explore the
      etiology of the vascular phenotype of Klotho deficiency and the therapeutic
      potential of Klotho in vascular disease.

PMID- 27693242
TI  - A quantitative study on splice variants of N-acylethanolamine acid amidase in
      human prostate cancer cells and other cells.
AB  - N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme, hydrolyzing various
      bioactive N-acylethanolamines with a preference for palmitoylethanolamide. Human
      NAAA mRNA was previously reported to consist of multiple 3'-end splice variants.
      However, their tissue distributions and roles have not been examined yet. In the
      present study, we first identified four major splice variants (tentatively
      referred to as a1, a2, b2, and c2) in a human prostate cancer cell line LNCaP,
      which were composed of exons 1-11, exons 1-10 and 12, exons 1-9 and 12, and exons
      1-8 and 12, respectively. We next developed quantitative polymerase chain
      reaction methods to individually quantify these NAAA variants as well as
      collectively measure all the variants. Among various human prostate cancer cells,
      the total levels of NAAA mRNAs in androgen-sensitive cells like LNCaP were higher
      than those in androgen-insensitive cells. In all of these prostate cells and
      other human cells, variants a1 and b2 showed the highest and lowest expression
      levels, respectively, among the four variants. Interestingly, ratios of the four
      variants were different by cell type. Variants a1 and a2 encoded the same full
      length NAAA protein, which was catalytically active, while b2 and c2 were
      translated to C-terminally truncated proteins. As expressed in HEK293 cells these
      truncated forms were detected as catalytically inactive precursor proteins, but
      not as mature forms. These results revealed wide distribution of multiple
      variants of NAAA mRNA in various human cells and suggested that the proteins from
      some variants are catalytically inactive.

PMID- 27693243
TI  - Benzyl isothiocyanate promotes apoptosis of oral cancer cells via an acute redox
      stress-mediated DNA damage response.
AB  - Benzyl isothiocyanate (BITC) is a cruciferous vegetable-derived compound with
      anticancer properties in human cancer cells. However, its anticancer potential
      and underlying mechanisms remain absent in human oral cancer cells. Results
      indicate that BITC inhibits growth, promotes G2/M phase arrest and triggers
      apoptosis of OC2 cells with a minimal toxicity to normal cells. BITC-induced cell
      death was completely prevented by pretreatment with thiol-containing redox
      compounds including N-acetyl-l-cysteine (NAC), glutathione (GSH), dithiothreitol,
      and 2-mercaptoethanol, but not free radical scavengers mito-TEMPO, catalase,
      apocynin, l-NAME and mannitol. BITC rapidly produced reactive oxygen species and
      nitric oxide, triggered oxidative DNA damage. BITC effectively decreased the
      intracellular GSH and GSH/GSSG ratio and redox balance recovery by thiol
      containing redox compounds, but not by free radical scavengers. Accordingly,
      redox stresses-DNA damage response (DDR) activated ATM, Chk2, p53, and p21 and
      subsequently resulted in G2/M phase arrest by inhibiting Cdc2 and cyclin B1.
      Notably, BITC-induced apoptosis was associated with reduced Mcl-1 and Bcl-2
      expression, diminished mitochondrial membrane potential (DeltaPsim), and
      increased PARP cleavage. These BITC-induced redox stress-mediated DDR and
      apoptosis could be blocked by NAC and GSH. Therefore, BITC can be a rational drug
      candidate for oral cancer and acted via a redox-dependent pathway.

PMID- 27693244
TI  - Impact of DNA repair on the dose-response of colorectal cancer formation induced
      by dietary carcinogens.
AB  - Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, which is
      causally linked to dietary habits, notably the intake of processed and red meat.
      Processed and red meat contain dietary carcinogens, including heterocyclic
      aromatic amines (HCAs) and N-nitroso compounds (NOC). NOC are agents that induce
      various N-methylated DNA adducts and O6-methylguanine (O6-MeG), which are removed
      by base excision repair (BER) and O6-methylguanine-DNA methyltransferase (MGMT),
      respectively. HCAs such as the highly mutagenic 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) cause bulky DNA adducts, which are removed
      from DNA by nucleotide excision repair (NER). Both O6-MeG and HCA-induced DNA
      adducts are linked to the occurrence of KRAS and APC mutations in colorectal
      tumors of rodents and humans, thereby driving CRC initiation and progression. In
      this review, we focus on DNA repair pathways removing DNA lesions induced by NOC
      and HCA and assess their role in protecting against mutagenicity and
      carcinogenicity in the large intestine. We further discuss the impact of DNA
      repair on the dose-response relationship in colorectal carcinogenesis in view of
      recent studies, demonstrating the existence of 'no effect' point of departures
      (PoDs), i.e. thresholds for genotoxicity and carcinogenicity. The available data
      support the threshold concept for NOC with DNA repair being causally involved.

PMID- 27693245
TI  - Ninety-day toxicity and single-dose toxicokinetics study of alpha-glycosyl
      isoquercitrin in Sprague-Dawley rats.
AB  - alpha-Glycosyl isoquercitrin (AGIQ) is highly absorbable and has been shown to
      possess antioxidative properties. Based on a favorable safety profile, it has
      been confirmed as generally recognized as safe (GRAS) compound by the FDA.
      Nevertheless, safety and toxicity information for AGIQ is still sparse.
      Therefore, the aim of this study was to test the safety and toxicokinetics of
      AGIQ in a 90-day study in 60 male and 60 female Sprague-Dawley rats at dietary
      doses up to 5%. All animals survived until scheduled euthanasia with no clinical
      signs of toxicity in any animal. AGIQ was rapidly absorbed with metabolism to
      quercetin and quercetin glucuronide at all dose levels. Statistically significant
      changes were noted in some tissue weights and clinical chemistry analytes,
      without evidence of systemic toxicity. The most prominent finding was systemic
      dose dependent yellow discoloration of bones of treated animals. However, no
      changes were observed microscopically, and this observation was concluded as
      toxicologically insignificant. The overall lack of adverse clinical signs,
      changes in body weight, feed consumption, clinical pathology parameters, and
      histopathological endpoints in animals administered AGIQ supports no observable
      adverse effect levels (NOAEL) of 5.0% in diet for both male and female rats (3461
      mg/kg/day and 3867 mg/kg/day, respectively).

PMID- 27693240
TI  - The impact of cerebrovascular aging on vascular cognitive impairment and
      dementia.
AB  - As human life expectancy rises, the aged population will increase. Aging is
      accompanied by changes in tissue structure, often resulting in functional
      decline. For example, aging within blood vessels contributes to a decrease in
      blood flow to important organs, potentially leading to organ atrophy and loss of
      function. In the central nervous system, cerebral vascular aging can lead to loss
      of the integrity of the blood-brain barrier, eventually resulting in cognitive
      and sensorimotor decline. One of the major of types of cognitive dysfunction due
      to chronic cerebral hypoperfusion is vascular cognitive impairment and dementia
      (VCID). In spite of recent progress in clinical and experimental VCID research,
      our understanding of vascular contributions to the pathogenesis of VCID is still
      very limited. In this review, we summarize recent findings on VCID, with a focus
      on vascular age-related pathologies and their contribution to the development of
      this condition.

PMID- 27693247
TI  - Value of Targeted Epidural Blood Patch and Management of Subdural Hematoma in
      Spontaneous Intracranial Hypotension: Case Report and Review of the Literature.
AB  - BACKGROUND: Spontaneous intracranial hypotension (SIH) is a more common than
      previously noted condition (1-2.5 per 50,000 persons) typically caused by
      cerebrospinal fluid (CSF) leakage. Initial treatment involves conservative
      therapies, but the mainstay of treatment for patients who fail conservative
      management is the epidural blood patch (EBP). Subdural hematoma (SDH) is a common
      complication occurring with SIH, but its management remains controversial.
      METHODS: In this report, we discuss a 62-year-old woman who presented with a 5
      week history of orthostatic headaches associated with nausea, emesis, and neck
      pain. Despite initial imaging being negative, the patient later developed classic
      imaging evidence characteristic of SIH. Magnetic resonance imaging was
      unrevealing for the source of the CSF leak. Radionuclide cisternography showed
      possible CSF leak at the right-sided C7-T1 nerve root exit site. After failing a
      blind lumbar EBP, subsequent targeted EBP at C7-T1 improved the patient's
      symptoms. Two days later she developed a new headache with imaging evidence of
      worsening SDH with midline shift requiring burr hole drainage. This yielded
      sustained symptomatic relief and resolution of previously abnormal imaging
      findings at 2-month follow-up. RESULTS: A literature review revealed 174 cases of
      SIH complicated by SDH. This revealed conflicting opinions concerning the
      management of this condition. CONCLUSIONS: Although blind lumbar EBP is often
      successful, targeted EBP has a lower rate of patients requiring a second EBP or
      other further treatment. On the other hand, targeted EBP has a larger risk
      profile. Depending on the clinic situation, treatment of the SDH via surgical
      evacuation may be necessary.

PMID- 27693248
TI  - Controlled lid-opening in Thermomyces lanuginosus lipase- An engineered switch
      for studying lipase function.
AB  - Here, we present a lipase mutant containing a biochemical switch allowing a
      controlled opening and closing of the lid independent of the environment. The
      closed form of the TlL mutant shows low binding to hydrophobic surfaces compared
      to the binding observed after activating the controlled switch inducing lid
      opening. We directly show that lipid binding of this mutant is connected to an
      open lid conformation demonstrating the impact of the exposed amino acid residues
      and their participation in binding at the water-lipid interface. The switch was
      created by introducing two cysteine residues into the protein backbone at sites
      86 and 255. The crystal structure of the mutant shows the successful formation of
      a disulfide bond between C86 and C255 which causes strained closure of the lid
      domain. Control of enzymatic activity and binding was demonstrated on substrate
      emulsions and natural lipid layers. The locked form displayed low enzymatic
      activity (~10%) compared to wild-type. Upon release of the lock, enzymatic
      activity was fully restored. Only 10% binding to natural lipid substrates was
      observed for the locked lipase compared to wild-type, but binding was restored
      upon adding reducing agent. QCM-D measurements revealed a seven-fold increase in
      binding rate for the unlocked lipase. The TlL_locked mutant shows structural
      changes across the protein important for understanding the mechanism of lid
      opening and closing. Our experimental results reveal sites of interest for future
      mutagenesis studies aimed at altering the activation mechanism of TlL and create
      perspectives for generating tunable lipases that activate under controlled
      conditions.

PMID- 27693246
TI  - Permeability Surface Area Product Using Perfusion Computed Tomography Is a
      Valuable Prognostic Factor in Glioblastomas Treated with Radiotherapy Plus
      Concomitant and Adjuvant Temozolomide.
AB  - OBJECTIVE: The current standard treatment protocol for patients with newly
      diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and
      adjuvant temozolomide (TMZ). We hypothesized that the permeability surface area
      product (PS) from a perfusion computed tomography (PCT) study is associated with
      sensitivity to TMZ. The aim of this study was to determine whether PS values were
      correlated with prognosis of GBM patients who received the standard treatment
      protocol. METHODS: This study included 36 patients with GBM that were newly
      diagnosed between October 2005 and September 2014 and who underwent preoperative
      PCT study and the standard treatment protocol. We measured the maximum value of
      relative cerebral blood volume (rCBVmax) and the maximum PS value (PSmax). We
      statistically examined the relationship between PSmax and prognosis using
      survival analysis, including other clinicopathologic factors (age, Karnofsky
      performance status [KPS], extent of resection, O6-methylguanine-DNA
      methyltransferase [MGMT] status, second-line use of bevacizumab, and rCBVmax).
      RESULTS: Log-rank tests revealed that age, KPS, MGMT status, and PSmax were
      significantly correlated with overall survival. Multivariate analysis using the
      Cox regression model showed that PSmax was the most significant prognostic
      factor. Receiver operating characteristic curve analysis showed that PSmax had
      the highest accuracy in differentiating longtime survivors (LTSs) (surviving more
      than 2 years) from non-LTSs. At a cutoff point of 8.26 mL/100 g/min, sensitivity
      and specificity were 90% and 70%, respectively. CONCLUSIONS: PSmax from PCT study
      can help predict survival time in patients with GBM receiving the standard
      treatment protocol. Survival may be related to sensitivity to TMZ.

PMID- 27693249
TI  - Exposure of cultured fibroblasts to the peptide PR-11 for the identification of
      induced proteome alterations and discovery of novel potential ligands.
AB  - The PR-11 peptide corresponds to the N-terminal and active region of the
      endogenously synthesized PR-39 molecule, of porcine origin. It is known to
      possess various biological effects including antimicrobial properties, angiogenic
      and anti-inflammatory activities. Apart from its reported activity as a
      proteasome inhibitor, a more comprehensive understanding of its function, at the
      molecular level, is still lacking. In this study, we used a label-free shotgun
      strategy to evaluate the proteomic alterations caused by exposure of cultured
      fibroblasts to the peptide PR-11. This approach revealed that more than half of
      the identified molecules were related to signalling, transcription and
      translation. Proteins directly associated to regulation of angiogenesis and
      interaction with the hypoxia-inducible factor 1-alpha (HIF-1alpha) were
      significantly altered. In addition, at least three differentially expressed
      molecules of the NF-kappaB pathway were detected, suggesting an anti-inflammatory
      property of PR-11. At last, we demonstrated novel potential ligands of PR-11,
      through its immobilization for affinity chromatography. Among the eluted
      molecules, gC1qR, a known complement receptor, appeared markedly enriched. This
      provided preliminary evidence of a PR-11 ligand possibly involved in the
      internalization of this peptide. Altogether, our findings contributed to a better
      understanding of the cellular pathways affected by PR-39 derived molecules.

PMID- 27693250
TI  - A cobalt-containing eukaryotic nitrile hydratase.
AB  - Nitrile hydratase (NHase), an industrially important enzyme that catalyzes the
      hydration of nitriles to their corresponding amides, has only been characterized
      from prokaryotic microbes. The putative NHase from the eukaryotic unicellular
      choanoflagellate organism Monosiga brevicollis (MbNHase) was heterologously
      expressed in Escherichia coli. The resulting enzyme expressed as a single
      polypeptide with fused alpha- and beta-subunits linked by a seventeen-histidine
      region. Size-exclusion chromatography indicated that MbNHase exists primarily as
      an (alphabeta)2 homodimer in solution, analogous to the alpha2beta2 homotetramer
      architecture observed for prokaryotic NHases. The NHase enzyme contained its full
      complement of Co(III) and was fully functional without the co-expression of an
      activator protein or E. coli GroES/EL molecular chaperones. The homology model of
      MbNHase was developed identifying Cys400, Cys403, and Cys405 as active site
      ligands. The results presented here provide the first experimental data for a
      mature and active eukaryotic NHase with fused subunits. Since this new member of
      the NHase family is expressed from a single gene without the requirement of an
      activator protein, it represents an alternative biocatalyst for industrial
      syntheses of important amide compounds.

PMID- 27693251
TI  - Inhibition of CDK7 bypasses spindle assembly checkpoint via premature cyclin B
      degradation during oocyte meiosis.
AB  - To ensure accurate chromosome segregation, the spindle assembly checkpoint (SAC)
      delays anaphase onset by preventing the premature activation of anaphase
      promoting complex/cyclosome (APC/C) until all kinetochores are attached to the
      spindle. Although an escape from mitosis in the presence of unsatisfied SAC has
      been shown in several cancer cells, it has not been reported in oocyte meiosis.
      Here, we show that CDK7 activity is required to prevent a bypass of SAC during
      meiosis I in mouse oocytes. Inhibition of CDK7 using THZ1 accelerated the first
      meiosis, leading to chromosome misalignment, lag of chromosomes during chromosome
      segregation, and a high incidence of aneuploidy. Notably, this acceleration
      occurred in the presence of SAC proteins including Mad2 and Bub3 at the
      kinetochores. However, inhibition of APC/C-mediated cyclin B degradation blocked
      the THZ1-induced premature polar body extrusion. Moreover, chromosomal defects
      mediated by THZ1 were rescued when anaphase onset was delayed. Collectively, our
      results show that CDK7 activity is required to prevent premature anaphase onset
      by suppressing the bypass of SAC, thus ensuring chromosome alignment and proper
      segregation. These findings reveal new roles of CDK7 in the regulation of meiosis
      in mammalian oocytes.

PMID- 27693253
TI  - BMP4 promotes a phenotype change of an esophageal squamous epithelium via up
      regulation of KLF4.
AB  - INTRODUCTION: Barrett's esophagus is a metaplastic lesion. However, the cellular
      and molecular mechanisms involved are poorly understood. The aim of this study
      was to investigate the roles of KLF4 and BMP4 in the pathogenesis of Barrett's
      epithelium. MATERIALS AND METHODS: Immunohistochemistry was used to analyse the
      expression of KLF4, BMP4, CDX2, MUC2 and MUC5AC in human esophageal specimens.
      Human esophageal squamous epithelial cells were subjected to bile acid treatment
      and used in transfection experiments. Quantitative real-time PCR and Western blot
      analysis were used to detect the expression of KLF4, BMP4, CDX2, MUC2 and MUC5ac.
      RESULTS: In human tissues, Barrett's epithelium strongly expressed BMP4, p
      Smad1/5/8 and KLF4. Furthermore, bile acids increased the expression of BMP4,
      KLF4, p-Smad1/5/8, CDX2, MUC2 and MUC5ac in esophageal epithelial cells in a time
      dependent manner. Moreover, we found that BMP4 up-regulated the expression of
      KLF4, CDX2, MUC2 and MUC5ac, but Noggin, a specific BMP4 antagonist, can block
      the expression of KLF4, CDX2, MUC2 and MUC5ac induced by BMP4. However, BMP4
      cannot induce the expression of CDX2, MUC2 and MUC5ac in cells with KLF4 siRNA,
      and Noggin cannot block the expression of KLF4, CDX2, MUC2 and MUC5ac in cells
      transfected with the KLF4 expression vector. CONCLUSION: Our results demonstrate
      that BMP4 promotes a phenotype change of an esophageal squamous epithelium via up
      regulation of KLF4.

PMID- 27693254
TI  - Hunger-Driven Motivational State Competition.
AB  - Behavioral choice is ubiquitous in the animal kingdom and is central to goal
      oriented behavior. Hypothalamic Agouti-related peptide (AgRP) neurons are
      critical regulators of appetite. Hungry animals, bombarded by multiple sensory
      stimuli, are known to modify their behavior during times of caloric need, rapidly
      adapting to a consistently changing environment. Utilizing ARCAgRP neurons as an
      entry point, we analyzed the hierarchical position of hunger related to rival
      drive states. Employing a battery of behavioral assays, we found that hunger
      significantly increases its capacity to suppress competing motivational systems,
      such as thirst, anxiety-related behavior, innate fear, and social interactions,
      often only when food is accessible. Furthermore, real-time monitoring of ARCAgRP
      activity revealed time-locked responses to conspecific investigation in addition
      to food presentation, further establishing that, even at the level of ARCAgRP
      neurons, choices are remarkably flexible computations, integrating internal
      state, external factors, and anticipated yield. VIDEO ABSTRACT.

PMID- 27693255
TI  - Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis
      Syndrome.
AB  - Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis
      syndrome (SMS), which is associated with diverse neurodevelopmental and
      behavioral symptoms as well as obesity. RAI1 encodes a nuclear protein but little
      is known about its molecular function or the cell types responsible for SMS
      symptoms. Using genetically engineered mice, we found that Rai1 preferentially
      occupies DNA regions near active promoters and promotes the expression of a group
      of genes involved in circuit assembly and neuronal communication. Behavioral
      analyses demonstrated that pan-neural loss of Rai1 causes deficits in motor
      function, learning, and food intake. These SMS-like phenotypes are produced by
      loss of Rai1 function in distinct neuronal types: Rai1 loss in inhibitory neurons
      or subcortical glutamatergic neurons causes learning deficits, while Rai1 loss in
      Sim1+ or SF1+ cells causes obesity. By integrating molecular and organismal
      analyses, our study suggests potential therapeutic avenues for a complex
      neurodevelopmental disorder.

PMID- 27693257
TI  - Reallocation of Olfactory Cajal-Retzius Cells Shapes Neocortex Architecture.
AB  - The neocortex undergoes extensive developmental growth, but how its architecture
      adapts to expansion remains largely unknown. Here, we investigated how early born
      Cajal-Retzius (CR) neurons, which regulate the assembly of cortical circuits,
      maintain a dense superficial distribution in the growing neocortex. We found that
      CR cell density is sustained by an activity-dependent importation of olfactory CR
      cells, which migrate into the neocortex after they have acted as axonal guidepost
      cells in the olfactory system. Furthermore, using mouse genetics, we showed that
      CR cell density severely affects the architecture of layer 1, a key site of input
      integration for neocortical networks, leading to an excitation/inhibition ratio
      imbalance. Our study reveals that neurons reenter migration several days after
      their initial positioning, thereby performing sequential developmental roles in
      olfactory cortex and neocortex. This atypical process is essential to regulate CR
      cell density during growth, which in turn ensures the correct wiring of
      neocortical circuitry. VIDEO ABSTRACT.

PMID- 27693252
TI  - TDP-43/FUS in motor neuron disease: Complexity and challenges.
AB  - Amyotrophic lateral sclerosis (ALS), a common motor neuron disease affecting two
      per 100,000 people worldwide, encompasses at least five distinct pathological
      subtypes, including, ALS-SOD1, ALS-C9orf72, ALS-TDP-43, ALS-FUS and Guam-ALS. The
      etiology of a major subset of ALS involves toxicity of the TAR DNA-binding
      protein-43 (TDP-43). A second RNA/DNA binding protein, fused in
      sarcoma/translocated in liposarcoma (FUS/TLS) has been subsequently associated
      with about 1% of ALS patients. While mutations in TDP-43 and FUS have been linked
      to ALS, the key contributing molecular mechanism(s) leading to cell death are
      still unclear. One unique feature of TDP-43 and FUS pathogenesis in ALS is their
      nuclear clearance and simultaneous cytoplasmic aggregation in affected motor
      neurons. Since the discoveries in the last decade implicating TDP-43 and FUS
      toxicity in ALS, a majority of studies have focused on their cytoplasmic
      aggregation and disruption of their RNA-binding functions. However, TDP-43 and
      FUS also bind to DNA, although the significance of their DNA binding in disease
      affected neurons has been less investigated. A recent observation of accumulated
      genomic damage in TDP-43 and FUS-linked ALS and association of FUS with neuronal
      DNA damage repair pathways indicate a possible role of deregulated DNA binding
      function of TDP-43 and FUS in ALS. In this review, we discuss the different ALS
      disease subtypes, crosstalk of etiopathologies in disease progression, available
      animal models and their limitations, and recent advances in understanding the
      specific involvement of RNA/DNA binding proteins, TDP-43 and FUS, in motor neuron
      diseases.

PMID- 27693256
TI  - The Dynamics of Functional Brain Networks: Integrated Network States during
      Cognitive Task Performance.
AB  - Higher brain function relies upon the ability to flexibly integrate information
      across specialized communities of brain regions; however, it is unclear how this
      mechanism manifests over time. In this study, we used time-resolved network
      analysis of fMRI data to demonstrate that the human brain traverses between
      functional states that maximize either segregation into tight-knit communities or
      integration across otherwise disparate neural regions. Integrated states enable
      faster and more accurate performance on a cognitive task, and are associated with
      dilations in pupil diameter, suggesting that ascending neuromodulatory systems
      may govern the transition between these alternative modes of brain function.
      Together, our results confirm a direct link between cognitive performance and the
      dynamic reorganization of the network structure of the brain.

PMID- 27693258
TI  - Clustering and Functional Coupling of Diverse Ion Channels and Signaling Proteins
      Revealed by Super-resolution STORM Microscopy in Neurons.
AB  - The fidelity of neuronal signaling requires organization of signaling molecules
      into macromolecular complexes, whose components are in intimate proximity. The
      intrinsic diffraction limit of light makes visualization of individual signaling
      complexes using visible light extremely difficult. However, using super
      resolution stochastic optical reconstruction microscopy (STORM), we observed
      intimate association of individual molecules within signaling complexes
      containing ion channels (M-type K+, L-type Ca2+, or TRPV1 channels) and G protein
      coupled receptors coupled by the scaffolding protein A-kinase-anchoring protein
      (AKAP)79/150. Some channels assembled as multi-channel supercomplexes.
      Surprisingly, we identified novel layers of interplay within macromolecular
      complexes containing diverse channel types at the single-complex level in sensory
      neurons, dependent on AKAP79/150. Electrophysiological studies revealed that such
      ion channels are functionally coupled as well. Our findings illustrate the novel
      role of AKAP79/150 as a molecular coupler of different channels that conveys
      crosstalk between channel activities within single microdomains in tuning the
      physiological response of neurons.

PMID- 27693259
TI  - From healthcare to health: A proposed pathway to population health.
AB  - Innovations in payment are encouraging clinical-community partnerships that
      address health determinants. However, little is known about how healthcare
      systems transform and partner to improve population health. We synthesized views
      of population health experts from nine organizations and illustrated the
      resulting model using examples from four health systems. The transformation
      requires a foundation of primary care, connectors and integrators that span the
      boundaries, sharing of goals among participants, aligned funding and incentives,
      and a supporting infrastructure, all leading to a virtuous cycle of
      collaboration. Policies are needed that will provide funding and incentives to
      encourage spread beyond early adopter organizations.

PMID- 27693260
TI  - A Dynamic Predictive Model for Progression of CKD.
AB  - BACKGROUND: Predicting the progression of chronic kidney disease (CKD) is vital
      for clinical decision making and patient-provider communication. We previously
      developed an accurate static prediction model that used single-timepoint
      measurements of demographic and laboratory variables. STUDY DESIGN: Development
      of a dynamic predictive model using demographic, clinical, and time-dependent
      laboratory data from a cohort of patients with CKD stages 3 to 5. SETTING &
      PARTICIPANTS: We studied 3,004 patients seen April 1, 2001, to December 31, 2009,
      in the outpatient CKD clinic of Sunnybrook Hospital in Toronto, Canada. CANDIDATE
      PREDICTORS: Age, sex, and urinary albumin-creatinine ratio at baseline. Estimated
      glomerular filtration rate (eGFR), serum albumin, phosphorus, calcium, and
      bicarbonate values as time-dependent predictors. OUTCOMES: Treated kidney
      failure, defined by initiation of dialysis therapy or kidney transplantation.
      ANALYTICAL APPROACH: We describe a dynamic (latest-available-measurement)
      prediction model using time-dependent laboratory values as predictors of outcome.
      Our static model included all 8 candidate predictors. The latest-available
      measurement model includes age and the latter 5 variables as time-dependent
      predictors. We used Cox proportional hazards models for time to kidney failure
      and compared discrimination, calibration, model fit, and net reclassification for
      the models. RESULTS: We studied 3,004 patients, who had 344 kidney failure events
      over a median follow-up of 3 years and an average of 5 clinic visits. eGFR was
      more strongly associated with kidney failure in the latest-available-measurement
      model versus the baseline visit static model (HR, 0.44 vs 0.65). The association
      of calcium level was unchanged, but male sex and phosphorus, albumin, and
      bicarbonate levels were no longer significant. Discrimination and goodness of fit
      showed incremental improvement with inclusion of time-dependent covariates
      (integrated discrimination improvement, 0.73%; 95% CI, 0.56%-0.90%). LIMITATIONS:
      Our data were derived from a nephrology clinic at a single center. We were unable
      to include time-dependent changes in albuminuria. CONCLUSIONS: A latest-available
      measurement predictive model with eGFR as a time-dependent predictor can
      incrementally improve risk prediction for kidney failure over a static model with
      only a single eGFR.

PMID- 27693262
TI  - Trends in Receipt of Intensive Procedures at the End of Life Among Patients
      Treated With Maintenance Dialysis.
AB  - BACKGROUND: Many dialysis patients receive intensive procedures intended to
      prolong life at the very end of life. However, little is known about trends over
      time in the use of these procedures. We describe temporal trends in receipt of
      inpatient intensive procedures during the last 6 months of life among patients
      treated with maintenance dialysis. STUDY DESIGN: Mortality follow-back study.
      SETTING & PARTICIPANTS: 649,607 adult Medicare beneficiaries on maintenance
      dialysis therapy who died in 2000 to 2012. PREDICTORS: Period of death (2000
      2003, 2004-2008, or 2009-2012), age at time of death (18-59, 60-64, 65-69, 70-74,
      75-79, 80-84, and >=85 years), and race/ethnicity (Hispanic, non-Hispanic black,
      or non-Hispanic white). OUTCOME: Receipt of an inpatient intensive procedure
      (defined as invasive mechanical ventilation/intubation, tracheostomy,
      gastrostomy/jejunostomy tube insertion, enteral or parenteral nutrition, or
      cardiopulmonary resuscitation) during the last 6 months of life. RESULTS:
      Overall, 34% of cohort patients received an intensive procedure in the last 6
      months of life, increasing from 29% in 2000 to 36% in 2012 (with 2000-2003 as the
      referent category; adjusted risk ratios [RRs] were 1.06 [95% CI, 1.05-1.07] and
      1.10 [95% CI, 1.09-1.12] for 2004-2008 and 2009-2012, respectively). Use of
      intensive procedures increased more markedly over time in younger versus older
      patients (comparing 2009-2012 to 2000-2003, adjusted RR was 1.18 [95% CI, 1.15
      1.20] for the youngest age group as opposed to 1.00 [95% CI, 0.96-1.04] for the
      oldest group). Comparing 2009 to 2012 to 2000 to 2003, the use of intensive
      procedures increased more dramatically for Hispanic patients than for non
      Hispanic black or non-Hispanic white patients (adjusted RRs of 1.18 [95% CI, 1.14
      1.22], 1.09 [95% CI, 1.07-1.11], and 1.10 [95% CI, 1.08-1.12], respectively).
      LIMITATIONS: Data sources do not provide insight into reasons for observed trends
      in the use of intensive procedures. CONCLUSIONS: Among patients treated with
      maintenance dialysis, there is a trend toward more frequent use of intensive
      procedures at the end of life, especially in younger patients and those of
      Hispanic ethnicity.

PMID- 27693263
TI  - Psychosexual Outcome Among Iranian Individuals With 5alpha-Reductase Deficiency
      Type 2 and Its Relationship With Parental Sexism.
AB  - INTRODUCTION: Few studies exist on the psychosexual outcome of homogeneous groups
      of individuals with 5alpha-reductase deficiency type 2 (5alpha-RD-2) and the
      relation between gender changes and parental hostile and benevolent sexism, which
      are two components of ambivalent sexism that assume a stereotypical approach
      toward women in an overtly negative way or a chivalrous, seemingly positive way.
      AIM: To report on the psychosexual outcome of individuals with 5alpha-RD-2 and to
      investigate its relation to the level of parental sexism in a relatively large
      sample of Iranians with 5alpha-RD-2. METHODS: Twenty participants (mean age =
      19.5 years, SD = 6.345) with a molecularly confirmed diagnosis of 5alpha-RD-2 who
      were assigned the female gender at birth and raised as female were included in
      the study. Participants and their parents were interviewed and their medical
      records were assessed. Parents also completed the Ambivalent Sexism Inventory
      (ASI), which includes hostile and benevolent sexism subscales. MAIN OUTCOME
      MEASURES: Psychosexual outcome and parental hostile and benevolent sexism
      measurements. RESULTS: Twelve of 20 participants (60%) were diagnosed with gender
      identity disorder not otherwise specified (Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, Text Revision). Ten of these transitioned to
      the male gender. The other 10 participants (50%), including the two diagnosed
      with gender identity disorder not otherwise specified, continued living in a
      female gender role. When comparing the ASI subscale scores between families of
      participants who changed their gender and those who did not, no significant
      difference was found for ASI total and hostile sexism scores, but there was a
      difference for benevolent sexism (P = .049): those whose daughters had changed
      their gender had higher benevolent sexism scores. CONCLUSION: The high prevalence
      of gender change and gender dysphoria reported in the literature was confirmed in
      this relatively large and homogeneous sample of Iranians with 5-alpha-RD-2 raised
      as female. Prenatal exposure to testosterone is hypothesized to play a role in
      the development of gender identity and sexual orientation, but parental attitudes
      also might be important. Although gender change in individuals with 5-alpha-RD-2
      is often attributed to high levels of hostile sexism in some cultures, our
      findings show this to be associated with benevolent sexism.

PMID- 27693261
TI  - Sleep Disorders, Restless Legs Syndrome, and Uremic Pruritus: Diagnosis and
      Treatment of Common Symptoms in Dialysis Patients.
AB  - Maintenance dialysis patients experience a high burden of physical and emotional
      symptoms that directly affect their quality of life and health care utilization.
      In this review, we specifically highlight common troublesome symptoms affecting
      dialysis patients: insomnia, restless legs syndrome, and uremic pruritus.
      Epidemiology, pathophysiology, and evidence-based current treatment are reviewed
      with the goal of providing a guide for diagnosis and treatment. Finally, we
      identify multiple additional areas of further study needed to improve symptom
      management in dialysis patients.

PMID- 27693264
TI  - Surgical Outcomes of Erectile Implants After Phalloplasty: Retrospective Analysis
      of 95 Procedures.
AB  - INTRODUCTION: The creation of a neophallus is a complex surgery that must meet
      functional and esthetic requirements. It is a long and demanding surgical process
      whose final stage consists of the implantation of a rigid or inflatable material
      that can be used to reproduce an erection. Data in the literature are scarce,
      with only the pioneering series present, which includes the use of the first
      devices and techniques. AIM: To report the outcome of patients with phalloplasty
      after implantation of erectile implants using standardized surgical techniques
      and the use of recent prosthesis types with or without a vascular graft. METHODS:
      This is a retrospective hospital-based analysis of all patients with phalloplasty
      who underwent implantation of an erectile prosthesis from March 2007 to May 2015.
      Factors associated with complications were investigated by multivariate logistic
      regression analysis. MAIN OUTCOME MEASURES: Early-onset (during the first month
      after surgery) and late-onset complications, including erosion, infections,
      malpositioning, and dysfunction. RESULTS: Sixty-nine patients were included in
      the study and 95 procedures were analyzed. After a median follow-up of 4 years
      (minimum = 169 days, maximum = 6.1 years), the original prosthesis was still in
      place in 43 patients (62.3%). Patients underwent phalloplasty after female-to
      male transsexualism (n = 62, 89.9%), malformation (n = 4, 5.8%), or trauma (n =
      3, 4.3%). The proportions for the different types of phalloplasty were 58% for
      forearm free flap phalloplasty (n = 40), 33.3% for suprapubic phalloplasty (n =
      23), and 7% for other (n = 6). The erectile prostheses used were the two-piece
      AMS Ambicor (n = 71, 74.7%), the Ambicor with a vascular graft (n = 19, 20.0%),
      and the AMS 700CXR, AMS 700CX, or AMS600-650 (n = 5, 5.2%). There were no early
      onset complications in 89 procedures (93.7%) and, when present, they were always
      related to infection (n = 4, 4.2%). Late-onset complications were erosion (n = 4,
      4.2%), infection (n = 4, 4.2%), dysfunction (n = 10, 10.5%), and malpositioning
      (n = 12, 12.6%). No significant difference was observed for malpositioning (12.7%
      vs 10.5%, P = .87) and dysfunction (7.0% vs 10.5%, P = .78) between the AMS
      Ambicor prosthesis and the Ambicor prosthesis with a vascular graft. CONCLUSION:
      This study provides updated data on complications after the implantation of
      erectile implants. Multicenter studies, including the evaluation of patient
      satisfaction, are needed to increase our understanding of factors associated with
      the outcomes.

PMID- 27693265
TI  - Differential Effects of Cyproterone Acetate vs Spironolactone on Serum High
      Density Lipoprotein and Prolactin Concentrations in the Hormonal Treatment of
      Transgender Women.
AB  - INTRODUCTION: Spironolactone and cyproterone acetate (CPA) are the two main
      antiandrogen medications used in feminizing hormone therapy in transgender women.
      Previous studies have suggested that these two agents might have opposite effects
      on high-density lipoprotein (HDL) level when used in this context, and limited
      data have suggested CPA increases prolactin more than spironolactone. AIM: To
      compare the effects of spironolactone and CPA on HDL and prolactin serum
      concentrations in transgender women. METHODS: A retrospective chart review was
      conducted at three clinical sites in Toronto, Ontario, Canada. Patients were
      selected if they (i) identified as a transgender woman, (ii) had newly started
      spironolactone or CPA with estrogen or restarted spironolactone or CPA after a
      washout period of at least 6 months, and (iii) had not used other antiandrogens
      within the previous 6 months. MAIN OUTCOME MEASURES: HDL and prolactin
      concentrations between the two treatment groups at baseline and at 12 months.
      RESULTS: Eighty-two patients were included in the spironolactone group and 31
      patients were included in the CPA group. Baseline HDL and prolactin levels were
      not significantly different between the two groups. At 12 months, HDL increased
      by 0.10 mmol/L (SD = 0.24) in the spironolactone group but decreased by 0.07
      mmol/L (SD = 0.21) in the CPA group (P = .002). The difference remained
      significant after adjusting for baseline HDL, use of lipid-lowering drugs, and
      age. The change in prolactin was +3.10 MUg/L (SD = 5.70) in the spironolactone
      group and +11.8 MUg/L (SD = 8.63) in the CPA group (P < 0.001). This difference
      also remained significant after adjusting for baseline prolactin level.
      CONCLUSION: These data suggest that spironolactone use in transgender women
      increases HDL levels and that CPA has the opposite effect. CPA also is associated
      with a larger increase in prolactin. These factors should be considered when
      choosing between these two antiandrogen agents.

PMID- 27693266
TI  - Imipramine ameliorates early life stress-induced alterations in synaptic
      plasticity in the rat lateral amygdala.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) are two opposite
      forms of synaptic plasticity at the cortical and thalamic inputs to the lateral
      amygdala (LA). It has been demonstrated that maternal separation (MS) of rat pups
      results in alterations in the potential for both pathways to undergo LTP and LTD
      in adolescence. Imipramine, a prototypic tricyclic antidepressant, has been shown
      to counteract some detrimental effects of MS on rat behavior, however it is not
      known whether MS-induced alterations in the potential for bidirectional synaptic
      plasticity in the LA could be reversed by imipramine treatment. To this end, rat
      pups were subjected to MS (3h/day) on postnatal days (PNDs) 1-21. On each of PNDs
      29-42, male rats previously subjected to MS were injected subcutaneously with
      imipramine (10mg/kg). Field potentials were recorded ex vivo from slices
      containing the LA and saturating levels of LTP and LTD were induced. At the
      thalamic input to the LA, both the maximum LTP and the maximum LTD were reduced
      in rats subjected to MS when compared to control animals, confirming earlier
      results. However, these effects were no longer present in rats subjected to MS
      and later treated with imipramine. At the cortical input in slices prepared from
      MS-subjected rats, an impairment of the maximum LTP and an enhancement of the
      maximum LTD were observed. At the cortical input in rats subjected to MS and
      receiving imipramine treatment, the level of LTD was comparable to control but
      imipramine did not restore the potential for LTP at this input. These results
      demonstrate that imipramine fully reverses the effects of MS in the thalamo
      amygdalar pathway, however, in the cortico-amygdalar pathway the reversal of the
      effects of MS by imipramine is partial.

PMID- 27693267
TI  - Complete genome sequence of Defluviimonas alba cai42T, a microbial
      exopolysaccharides producer.
AB  - Defluviimonas alba cai42T, isolated from the oil-production water in Xinjiang
      Oilfield in China, has a strong ability to produce exopolysaccharides (EPS). We
      hereby present its complete genome sequence information which consists of a
      circular chromosome and three plasmids. The strain characteristically contains
      various genes encoding for enzymes involved in EPS biosynthesis, modification,
      and export. According to the genomic and physiochemical data, it is predicted
      that the strain has the potential to be utilized in industrial production of
      microbial EPS.

PMID- 27693269
TI  - Definition of plastic surgery: A historical perspective.

PMID- 27693268
TI  - ORF7 from Amycolatopsis orientalis catalyzes decarboxylation of Ndelta
      methylarginine and amine oxidation of arginine: Biosynthetic implications.
AB  - A key step in the biosynthesis of the polyene polyketide ECO-0501 by
      Amycolatopsis orientalis ATCC 43491 is thought to involve oxidative
      decarboxylation of arginine or Ndelta-methylarginine to the corresponding primary
      amide. This reaction is the centerpiece of a recently identified biosynthetic
      cassette that generates 4-guanidinobutyryl thioesters to serve as starter units
      for polyketide synthesis. We examined the reaction of ORF7, the predicted ECO
      0501 biosynthetic decarboxylase, with arginine, and saw no evidence of
      decarboxylation. Instead, we observed exclusive amine oxidation to generate 2
      oxoarginine, with a kcat/KM,Arg of 5.6*106M-1s-1, typical of values measured for
      physiological amino acid decarboxylases. In contrast, when ORF7 was incubated
      with Ndelta-methylarginine, we observed exclusive decarboxylation to generate 4
      (N1-methylguanidino)butyramide. These differing reactive pathways provide insight
      into the biosyntheses of guanidinobutyryl-derived polyketides and demonstrate the
      biosynthetic versatility of arginine-processing decarboxylases. In addition, it
      suggests that ORF7 may be an incisive model system for dissecting the
      determinants of flavoprotein-catalyzed oxidase and monooxygenase modes of
      reactivity.

PMID- 27693270
TI  - Selection of recipient vessels for free flap following intra-arterial
      chemoradiotherapy.
AB  - OBJECTIVE: This study aims at selecting recipient vessels for free flap following
      intra-arterial chemoradiotherapy. At present, many centers combine intra-arterial
      chemotherapy and concomitant radiotherapy for treating head and neck cancer with
      favorable results. However, some patients develop recurrent, residual
      disease/complications after completing treatment protocols and thus require free
      flap surgery. The feasibility of microsurgery following intra-arterial
      chemoradiotherapy remains unclear. STUDY DESIGN AND METHODS: We retrospectively
      analyzed 730 patients who underwent free-flap surgery for managing treatment
      related complications/defects following head and neck surgery from January 1999
      to February 2012. All patients were categorized into two groups according to the
      presence (group A)/absence (group B) of a history of intra-arterial chemotherapy.
      Microvascular revision rates were compared between the groups. In group A, the
      correlation between catheterization sites and recipient vessels used for
      microsurgery was assessed. RESULTS: A total of 769 free flaps were created in 730
      patients and comprised 36 and 733 flaps in groups A and B, respectively.
      Microvascular revision rates were 2.8% (1/36) and 4.2% (31/733) in groups A and
      B, respectively, with no significant difference observed between the groups. No
      statistically significant difference was observed when only cases of arterial
      thrombosis were included. Vessels used for recipient anastomoses were not
      directly exposed to intra-arterially injected agents. CONCLUSION: Preoperative
      intra-arterial chemoradiotherapy does not significantly increase the risk of
      microvascular revisions, particularly artery-related revisions, if vessels
      selectively catheterized and perfused with chemotherapeutic agents during intra
      arterial chemotherapy are avoided as recipient vessels.

PMID- 27693271
TI  - An analysis of pose in 3D stereophotogrammetry of the breast.
AB  - BACKGROUND: Volume of the breast can be objectively measured by three-dimensional
      (3D) photographs. This study describes the analysis of three different positions
      of the patient in image acquisition, in order to find the best pose for
      reproducible 3D photographs of the breasts. METHOD: Twenty-four patients were
      included between February and September 2014 in a consecutive way. Data were
      collected prospectively. 3D photographs were acquired using a
      stereophotogrammetry system. Images were taken twice in three different positions
      (arms behind the back, arms placed on the hips and arms horizontally placed).
      Surface based matching was applied and the absolute mean distance between the
      surfaces of both 3D models of the same position was calculated. This difference
      measure represents the similarity of the photographs. RESULTS: Univariate ANOVA
      showed a significant difference in distance between the three positions (sum of
      squares 1.12, p < 0.001). The horizontal position presented the lowest absolute
      mean distance (0.45 mm). Additional post hoc multiple comparisons analysis
      revealed a statistically significant difference between the distances of
      horizontal and back position (-0.22 mm, p < 0.001) and of back and hip position
      (0.13 mm, p = 0.009), with better results of the horizontal and hip positions,
      respectively. CONCLUSION: Standardization of 3D acquisition in pre- and
      postoperative breast imaging could improve imaging reproducibility. Based on the
      results of this study, we recommend a pose with the arms in a horizontal
      position.

PMID- 27693272
TI  - Lymphoscintigraphy mapping of truncal malignant melanoma: A study of 212 patients
      at the Christie NHS Foundation Trust.
AB  - BACKGROUND AND PURPOSE: Malignant melanoma (MM) on the trunk, because of its
      anatomical location, has multiple potential lymphatic basins to which to drain.
      The aim of this study is to map the location of the sentinel lymph node (SLN) on
      the basis of the anatomical location of the primary malignant melanoma on the
      trunk. METHODS: Patients diagnosed with MM on the trunk who had undergone a SLN
      biopsy from January 2006 to March 2015 were identified in the Christie NHS
      Foundation Trust through a computer database search. The anterior and posterior
      surfaces of the trunk were divided into four sections each. RESULTS: A total of
      212 patients were evaluated. MM was more common on the posterior trunk,
      accounting for 73% of cases, and 57% of melanomas were on the right side of the
      trunk. The axillary basins were involved in drainage in 91.5% of all truncal
      melanomas. Drainage was to a single lymphatic basin in 68.3% of cases. The
      incidence of drainage to multiple lymphatic basins was not uniform for the
      anterior and posterior surfaces of the trunks. CONCLUSION: One-third of MM on the
      posterior surface of the trunk will drain to multiple basins. Around 50% of the
      melanomas of the upper back drain to a contralateral basin. Independent of the
      location of the MM, the axillary basins were the most common location of
      drainage, with a total of 91% of the cohort. Therefore, the location of the SLN
      could be predicted, depending on the location of the MM on the trunk.

PMID- 27693273
TI  - Surgical anatomy of the first extensor compartment: A systematic review and
      comparison of normal cadavers vs. De Quervain syndrome patients.
AB  - PURPOSE: De Quervain syndrome or tenosynovitis is a common wrist pathology caused
      by stenosing tenosynovitis of the first dorsal compartment. Multiple studies have
      demonstrated significant anatomic variation within the first extensor
      compartment. METHODS: The terms "De Quervain's tenosynovitis" and "first extensor
      compartment anatomy" were comprehensively searched using the PubMed, MEDLINE, and
      Cochrane database. The presence of a septum within the first dorsal compartment,
      the number of APL (abductor pollicis longus), and EPB (extensor pollicis brevis)
      tendon slips were identified. RESULTS: A total of 574 articles were identified on
      initial search, of which 21 met inclusion criteria. There were 1901 normal
      cadaver specimens and 470 surgically treated De Quervain disease patients, whose
      data were available. A septum was present in 43.7% of normal cadavers versus
      62.2% De Quervain patients with 58.5% (327 of 559) of the septi characterized as
      incomplete. There was a difference in the number of APL tendons with a single APL
      tendon slip noted in 18.3% of normal cadavers (200/1096) versus 27.2% of De
      Quervain patients (87/230). There was a difference in the number of EPB tendons
      between the normal cadavers and De Quervain's wrists with 2 or more EPB tendinous
      slips observed in 5.9% of normal cadavers compared with 2.9% of De Quervain
      patients. CONCLUSION: Significant anatomic variability exists within the first
      extensor compartment. Patients with De Quervain disease were more likely to have
      a septum dividing the compartment and a single slip of APL. These variations are
      clinically relevant in the pathophysiology and treatment of De Quervain's
      tenosynovitis. TYPE OF STUDY: Prognostic studies. LEVEL OF EVIDENCE: Level III.

PMID- 27693274
TI  - Anti Xa oral anticoagulants inhibit in vivo platelet activation by modulating
      glycoprotein VI shedding.
AB  - Anti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess
      antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim
      of the study was to compare the effect on platelet activation of two anti Xa
      NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the
      potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a
      protein involved in platelet activation. We performed a cross-sectional including
      AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or
      rivaroxaban 20mg/day (n=40). Patients were balanced for sex, age and
      cardiovascular risk factors. Platelet activation by urinary excretion of 11
      dehydro-thromboxane (Tx) B2 and soluble GPVI (sGPVI) were analysed at baseline
      and after 3 months of treatment. Baseline TxB2 value was 155.2+/-42.7ng/mg
      creatinine. The 3 months-variation of urinary excretion of TxB2 was -6.5% with
      warfarin (p=0.197), -29% with apixaban (p<0.001) and -31% with rivaroxaban
      (p<0.001). Use of anti Xa NOACs was independently associated to the variation of
      urinary TxB2 (B: -0.469, p<0.001), after adjustment for clinical characteristics;
      sGPVI was significantly lower in patients treated with NOACs at 3 months
      (p<0.001), while only a trend for the warfarin group (p=0.116) was observed. The
      variation of sGPVI was correlated with that of TxB2 in the NOACs group (Rs:
      0.527, p<0.001). In 15 patients (5 per each group) platelet recruitment was
      significantly lowered at 3 months by NOACs (p<0.001), but not by warfarin. The
      study provides evidence that anti Xa NOACs significantly inhibit urinary TxB2
      excretion compared to warfarin, suggesting that NOACs possess antiplatelet
      property.

PMID- 27693275
TI  - The effect of morbid obesity on morphine glucuronidation.

PMID- 27693277
TI  - The effect of morbid obesity on morphine glucuronidation.

PMID- 27693276
TI  - Doxorubicin loaded gold nanoparticles: Implication of passive targeting on
      anticancer efficacy.
AB  - The present work aims to investigate targeting potential of doxorubicin (Dox)
      functionalized gold nanoparticles (D-GNPs) for treatment of chemically induced
      fibrosarcoma in mice. Carrier GNPs were synthesised by green chemistry method and
      loaded with doxorubicin by incubation method. D-GNPs were studied for its
      biocompatibility using normal mouse fibroblasts (L929) and found to be cell
      compatible and non-toxic. D-GNPs (at a dose of 2.5, 2 and 1.5mg/kg equivalent to
      Dox) demonstrated passive targeting measured as function of antitumor efficacy
      against chemical induced fibrosarcoma which showed higher latency to the tumour
      growth as compared to free Dox (2.5mg/kg). D-GNPs exhibited significantly higher
      therapeutic anticancer efficacy (~81% tumour suppression at dose of 2.5mg/kg
      equivalent to Dox) in the same model as compared to that of free doxorubicin
      (~48% tumour suppression at dose of 2.5mg/kg). Safety profile and targeting
      efficiency of developed formulation was established by assessing cardiac and
      blood markers.

PMID- 27693278
TI  - [Pediatric kidney transplantation].
AB  - AIMS: To describe indications, surgical aspects, results and outcomes of kidney
      transplantation in children. MATERIAL AND METHODS: An exhaustive systematic
      review of the scientific literature was performed in the Medline database
      (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different
      associations of the following keywords (MESH): "kidney transplantation",
      "pediatric", "children", "outcomes". Publications obtained were selected based on
      methodology, language, date of publication (last 10 years) and relevance.
      Prospective and retrospective studies, in English or French, review articles;
      meta-analysis and guidelines were selected and analyzed. This search found 2608
      articles. After reading titles and abstracts, 18 were included in the text based
      on their relevance. RESULTS: Kidney transplantation is the gold-standard
      treatment for end stage renal kidney disease in children. The surgical procedure
      is well standardized with a retroperitoneal approach when child and kidney size
      allow it or a transperitoneal approach in child less than 15 kg and big size
      kidney graft. Anastomosis sites include iliac vessels in the retroperitoneal
      approach, and inferior vena cava and aorta in case of transperitoneal procedure.
      Ureteral reimplantation used most of the time a Campos Freire technique.
      Sometimes, particular conditions in the recipient (such as vena cava thrombosis)
      required procedure adaptation. CONCLUSION: Graft survival dramatically increased
      over the past few years and is now superior to those observed in adult kidney
      transplantation, particularly in experienced team with microsurgery skills.
      Immunosuppressive treatments are similar to adults. Viral infections and post
      transplant lymphoproliferative disorder are the main complications of renal
      transplantation in children and may lead to lethal outcomes. An increase graft
      loss is observed during boyhood due to immunosuppressive drugs uncompliance.

PMID- 27693279
TI  - [Ischemia-reperfusion. Preservation solution and hypothermic machine perfusion].
AB  - AIMS: To describe ischemia-reperfusion mechanisms, the impact on kidney graft and
      strategies developed to minimize ischemia-reperfusion damages. MATERIAL AND
      METHODS: An exhaustive systematic review of the scientific literature was
      performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase
      (http://www.embase.com) using different associations of the following keywords:
      ischemia-reperfusion; organ preservation; hypothermic machine perfusion; renal
      transplantation. Publications obtained were selected based on methodology,
      language, date of publication and relevance. Prospective and retrospective
      studies, in English or French, review articles; meta-analysis and guidelines were
      selected and analyzed. This search found 1293 articles. After reading titles and
      abstracts, 88 were included in the text, based on their relevance. RESULTS:
      Ischemia-reperfusion injuries occur when blood supply of an organ is interrupted
      or drastically reduced. Ischemic damages started immediately after arterial
      clamping in donor, persist during cold ischemia time, and are increased after
      reperfusion because of increased oxygen levels, organ warming and recipient cell
      infiltration. Besides metabolic and biologic impact, IR induced dramatic
      immunologic impact through immunologic cells activation. CONCLUSIONS: Knowledge
      of IR mechanisms is crucial to improve organ storage strategies and to decreased
      impact of IR on long-term graft and patient survival. Hypothermic machine
      perfusion was associated with prolonged graft survival versus cold storage.
      Principles and results of hypothermic machine perfusion will be reported.

PMID- 27693280
TI  - Emergency department point-of-care ultrasound in out-of-hospital and in-ED
      cardiac arrest.
AB  - BACKGROUND: Point-of-care ultrasound has been suggested to improve outcomes from
      advanced cardiac life support (ACLS), but no large studies have explored how it
      should be incorporated into ACLS. Our aim was to determine whether cardiac
      activity on ultrasound during ACLS is associated with improved survival. METHODS:
      We conducted a non-randomized, prospective, protocol-driven observational study
      at 20 hospitals across United States and Canada. Patients presenting with out-of
      hospital arrest or in-ED arrest with pulseless electrical activity or asystole
      were included. An ultrasound was performed at the beginning and end of ACLS. The
      primary outcome was survival to hospital admission. Secondary outcomes included
      survival to hospital discharge and return of spontaneous circulation. FINDINGS:
      793 patients were enrolled, 208 (26.2%) survived the initial resuscitation, 114
      (14.4%) survived to hospital admission, and 13 (1.6%) survived to hospital
      discharge. Cardiac activity on US was the variable most associated with survival
      at all time points. On multivariate regression modeling, cardiac activity was
      associated with increased survival to hospital admission (OR 3.6, 2.2-5.9) and
      hospital discharge (OR 5.7, 1.5-21.9). No cardiac activity on US was associated
      with non-survival, but 0.6% (95% CI 0.3-2.3) survived to discharge. Ultrasound
      identified findings that responded to non-ACLS interventions. Patients with
      pericardial effusion and pericardiocentesis demonstrated higher survival rates
      (15.4%) compared to all others (1.3%). CONCLUSION: Cardiac activity on ultrasound
      was the variable most associated with survival following cardiac arrest.
      Ultrasound during cardiac arrest identifies interventions outside of the standard
      ACLS algorithm.

PMID- 27693284
TI  - Reply by Authors.

PMID- 27693281
TI  - Self-assessment of social cognitive ability in individuals with schizophrenia:
      Appraising task difficulty and allocation of effort.
AB  - Patients with severe mental illnesses manifest substantial deficits in self
      assessment of the abilities that impact everyday functioning. This study compares
      patients with schizophrenia to healthy individuals on their social cognitive
      performance, their assessment of that performance, and the convergence between
      performance and indicators of effort in solving tasks. Patients with
      schizophrenia (n=57) and healthy controls (HC; n=47) completed the Bell-Lysaker
      Emotion Recognition Test (BLERT), a psychometrically sound assessment of emotion
      recognition. Participants rated their confidence in the accuracy of their
      responses after each item. Participants were instructed to respond as rapidly as
      possible without sacrificing accuracy; the time to complete each item was
      recorded. Patients with schizophrenia performed less accurately on the BLERT than
      HC. Both patients and HC were more confident on items that they correctly
      answered than for items with errors, with patients being less confident overall;
      there was no significant interaction for confidence between group and accuracy.
      HC demonstrated a more substantial adjustment of response time to task difficulty
      by taking considerably longer to solve items that they got wrong, whereas
      patients showed only a minimal adjustment. These results expand knowledge about
      both self-assessment of social cognitive performance and the ability to appraise
      difficulty and adjust effort to social cognitive task demands in patients with
      schizophrenia.

PMID- 27693282
TI  - Pattern of activation during delayed matching to sample task predicts functional
      outcome in people at ultra high risk for psychosis.
AB  - BACKGROUND: Clinical outcomes in people identified as at ultra-high risk (UHR)
      for psychosis are remarkably heterogeneous, and are difficult to predict on the
      basis of the presenting clinical features. Individuals at UHR are at risk of poor
      functional outcome regardless of development of psychotic disorder. The aim of
      the present study was to assess whether there is a relationship between
      functional neuroimaging measures at presentation and functional outcome as
      measured by the GAF three years after scanning. METHODS: Functional magnetic
      resonance imaging (fMRI) data were collected during an object working memory task
      in 34 ultra-high risk (UHR) subjects and 20 healthy controls. On the basis of
      their GAF scores at follow up, the UHR participants were divided into subgroups
      with good and poor functional outcomes, respectively. RESULTS: At baseline, the
      UHR group differed from controls in showing altered frontal and cuneus/posterior
      cingulate activation. Significant group x task interactions were found in the
      left cuneus and posterior cingulate gyrus, reflecting differential responses to
      the task conditions. Within the UHR sample, the subgroup with a poor functional
      outcome exhibited altered activation in frontal, temporal and striatal regions,
      and reduced deactivation within default-mode network regions, relative to those
      with a good outcome. Within the whole UHR sample, in these regions the local task
      response was correlated with the GAF score at follow up. CONCLUSIONS: The
      findings suggest a potential role of functional neuroimaging in the prediction of
      outcomes in people at high clinical risk of psychosis.

PMID- 27693285
TI  - Re: Advantages of Reduced Prophylaxis after Tubularized Incised Plate Repair of
      Hypospadias: S. Zeiai, A. Nordenskjold and M. Fossum J Urol 2016;196:1244-1249.

PMID- 27693283
TI  - Re: A Mathematical Method to Calculate Tumor Contact Surface Area: An Effective
      Parameter to Predict Renal Function after Partial Nephrectomy: P.-F. Hsieh, Y.-D.
      Wang, C.-P. Huang, H.-C. Wu, C.-R. Yang, G.-H. Chen and C.-H. Chang J Urol
      2016;196:33-40.

PMID- 27693286
TI  - Re: Use of Pediatric Open, Laparoscopic and Robot-Assisted Laparoscopic Ureteral
      Reimplantation in the United States: 2000 to 2012: D. K. Bowen, M. A. Faasse, D.
      B. Liu, E. M. Gong, B. W. Lindgren and E. K. Johnson J Urol 2016;196:207-212.

PMID- 27693287
TI  - Reply by Authors.

PMID- 27693288
TI  - Implementation of a Comprehensive Post-Discharge Venous Thromboembolism
      Prophylaxis Program for Abdominal and Pelvic Surgery Patients.
AB  - BACKGROUND: Prophylactic anticoagulation is routinely used in the inpatient
      setting; however, the risk of venous thromboembolism (VTE) remains elevated after
      discharge. Extensive evidence and clinical guidelines suggest post-discharge VTE
      prophylaxis is critical in at-risk populations, but it remains severely underused
      in practice. STUDY DESIGN: We performed a single-institution retrospective,
      nonrandomized, pre- and post-intervention analysis of a systematic post-discharge
      pharmacologic prophylaxis program against the primary end point, which is post
      discharge symptomatic VTE. An institutional American College of Surgeons NSQIP
      dataset was used to identify patients and outcomes. Patients undergoing major
      abdominal surgery for malignancy or inflammatory bowel disease were eligible for
      the post-discharge VTE prevention program. RESULTS: Among 1,043 patients who
      underwent abdominal surgery for malignancy or inflammatory bowel disease, 800
      (77%) were in the pre-intervention cohort and 243 (23%) patients were in the post
      intervention cohort. Rates of inpatient VTE did not significantly differ between
      cohorts (0.7%, n = 6 pre-intervention vs 1.7%, n = 4 post-intervention; p =
      0.25). However, compared with the pre-intervention cohort, patients in the post
      intervention cohort demonstrated a significantly lower post-discharge VTE rate
      (2.5%, n = 20 pre-intervention vs 0.0%, n = 0 post-intervention; p < 0.01).
      CONCLUSIONS: A systematic post-discharge VTE prophylaxis program including
      provider education, local guideline adaptation, bedside medication delivery, and
      education for at-risk patients, was associated with significantly fewer post
      discharge VTE events.

PMID- 27693289
TI  - Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected
      calves generated under experimental conditions.
AB  - 'HoBi'-like virus is an atypical group within the Pestivirus genus that is
      implicated in economic losses for cattle producers due to both acute and
      persistent infections. Pestivirus strains exist as quasispecies (swarms of
      individual viruses) in infected animals and the viral populations making up the
      quasispecies differ widely in size and diversity in each animal. In the present
      study the viral quasispecies circulating in persistently infected (PI) calves,
      generated and maintained under experimental conditions using two different 'HoBi'
      like strains, was observed over time. An increase in genetic variability and the
      development of certain mutations was observed over time. Mutations observed
      included the loss of a putative N-linked glycosylation site in the E2 region and
      the change of specific residues in E1/E2. It is hypothesized that these changes
      may be the results on continued adaption of the pestivirus to individual hosts.
      This is the first study characterizing variation in the viral swarms of animals
      persistently infected with HoBi-like viruses over time. Studies of the shifts in
      PI viral swarms will contribute to our understanding of the host and viral
      mechanisms that function in the maintenance of pestivirus persistent infections.

PMID- 27693290
TI  - Recent advances in inferring viral diversity from high-throughput sequencing
      data.
AB  - Rapidly evolving RNA viruses prevail within a host as a collection of closely
      related variants, referred to as viral quasispecies. Advances in high-throughput
      sequencing (HTS) technologies have facilitated the assessment of the genetic
      diversity of such virus populations at an unprecedented level of detail. However,
      analysis of HTS data from virus populations is challenging due to short, error
      prone reads. In order to account for uncertainties originating from these
      limitations, several computational and statistical methods have been developed
      for studying the genetic heterogeneity of virus population. Here, we review
      methods for the analysis of HTS reads, including approaches to local diversity
      estimation and global haplotype reconstruction. Challenges posed by aligning
      reads, as well as the impact of reference biases on diversity estimates are also
      discussed. In addition, we address some of the experimental approaches designed
      to improve the biological signal-to-noise ratio. In the future, computational
      methods for the analysis of heterogeneous virus populations are likely to
      continue being complemented by technological developments.

PMID- 27693291
TI  - C-terminal domain on the outer surface of the Macrobrachium rosenbergii nodavirus
      capsid is required for Sf9 cell binding and internalization.
AB  - We have shown that Macrobrachium rosenbergii nodavirus (MrNV) was able to infect
      Sf9 cells and that MrNV virus-like particles (MrNV-VLPs) were capable
      nanocontainers for delivering nucleic acid-based materials. Here, we demonstrated
      that chymotryptic removal of a C-terminal peptide and its truncated variant (F344
      MrNV-VLPs) exhibited a drastically reduced ability to interact and internalize
      into Sf9 cells. Electron microscopic observations revealed that the loss of C
      terminal domain either from enzyme hydrolysis or genetic truncation did not
      affect the generated MrNV-VLPs' icosahedral conformation, but did drastically
      affect the VLPs' internalization ability into Sf9 cells. Homology-based modelling
      of the MrNV capsid with other icosahedral capsid models revealed that this
      chymotrypsin-sensitive C-terminal domain was not only exposed on the capsid
      surface, but also constituted the core of the viral capsid protrusion. These
      results therefore suggest the importance of the C-terminal domain as a structure
      for targeted cell interaction which is presumably localized at the protruding
      domain. This work thus provided the functional insights into the role of the MrNV
      C-terminal domain in viral entry into Sf9 cells and lead to the development of
      strategies in combatting MrNV infection in susceptible cells.

PMID- 27693292
TI  - Predictors and patterns of weight gain during treatment for tuberculosis in the
      United States of America.
AB  - OBJECTIVES: Patients with tuberculosis (TB) often present with weight loss. Lack
      of weight gain with TB treatment has been associated with treatment failure. The
      purpose of this study was to examine patterns of weight gain in patients with TB
      and determine the disease characteristics that predict weight gain. METHODS: This
      was a retrospective cohort study of adults with TB treated in a county health
      system in the USA. Demographic, clinical, radiographic, and microbiological data
      were recorded in addition to monthly weights during treatment. RESULTS: Overall,
      patients had a significant change in weight over the course of treatment
      (p<0.0001). After 2 months of treatment, 31.9% of patients had gained at least 5%
      body weight; by the end of treatment, 62.4% of patients had gained at least 5%
      weight. Patients who gained weight did so in a linear fashion throughout
      treatment. Cavitary and extensive disease, a positive smear, and a positive
      culture were predictors of weight gain (p<0.05). No patients had relapses during
      the time period of the study. CONCLUSIONS: Only a subset of patients treated for
      TB gain significant weight. A greater burden of disease was predictive of weight
      gain.

PMID- 27693293
TI  - NIRS-EEG joint imaging during transcranial direct current stimulation: Online
      parameter estimation with an autoregressive model.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to
      perturb both cortical neural activity and hemodynamics during (online) and after
      the stimulation, however mechanisms of these tDCS-induced online and after
      effects are not known. Here, online resting-state spontaneous brain activation
      may be relevant to monitor tDCS neuromodulatory effects that can be measured
      using electroencephalography (EEG) in conjunction with near-infrared spectroscopy
      (NIRS). METHOD: We present a Kalman Filter based online parameter estimation of
      an autoregressive (ARX) model to track the transient coupling relation between
      the changes in EEG power spectrum and NIRS signals during anodal tDCS (2mA,
      10min) using a 4*1 ring high-definition montage. RESULTS: Our online ARX
      parameter estimation technique using the cross-correlation between log (base-10)
      transformed EEG band-power (0.5-11.25Hz) and NIRS oxy-hemoglobin signal in the
      low frequency (<=0.1Hz) range was shown in 5 healthy subjects to be sensitive to
      detect transient EEG-NIRS coupling changes in resting-state spontaneous brain
      activation during anodal tDCS. Conventional sliding window cross-correlation
      calculations suffer a fundamental problem in computing the phase relationship as
      the signal in the window is considered time-invariant and the choice of the
      window length and step size are subjective. Here, Kalman Filter based method
      allowed online ARX parameter estimation using time-varying signals that could
      capture transients in the coupling relationship between EEG and NIRS signals.
      CONCLUSION: Our new online ARX model based tracking method allows continuous
      assessment of the transient coupling between the electrophysiological (EEG) and
      the hemodynamic (NIRS) signals representing resting-state spontaneous brain
      activation during anodal tDCS.

PMID- 27693294
TI  - Assessment of axonal excitability properties in two branches of the human facial
      nerve.
AB  - BACKGROUND: Axonal excitability methods have an established role in determining
      the biophysical properties of human axons in the clinical setting. The
      translation and refinement of these techniques for application to the facial
      nerve is important for advancing the pathophysiological understanding of facial
      nerve disorders. Facial nerve disorders are common and debilitating, yet in most
      cases diagnosis is based on clinical judgment alone. The pathophysiology of most
      causes of facial palsy remains unclear. NEW METHOD: Novel techniques for the
      acquisition of facial nerve excitability properties were developed based on
      anatomical and surgical landmarks for two facial nerve branches. Zygomatic branch
      stimulation with nasalis recording and marginal mandibular branch stimulation
      with depressor angularis oris (DAO) recording were used. Comparisons were made
      between the two branches and with the median nerve, and the relationship between
      gender, age and nerve properties was explored through subgroup analysis. RESULTS:
      A full set of recordings were obtained in all participants across a wide age
      range. 27 nasalis recordings and 19 DAO recordings were completed and analysed.
      The studies were well tolerated in all participants. Excitability parameters were
      found to be similar for both branches of the facial nerve. COMPARISON WITH
      EXISTING METHOD: Axonal excitability has proven to be of significant value in the
      study of motor and sensory neuropathy, however previous experience with facial
      nerve techniques has been limited. This study establishes normative data and a
      consistent technique for the application of axonal excitability testing to the
      study of facial nerve properties.

PMID- 27693295
TI  - Strength of obesity prevention interventions in early care and education
      settings: A systematic review.
AB  - TIME AND PLACE OF STUDY: 2010-2015; INTERNATIONAL: Given the high levels of
      obesity in young children, numbers of children in out-of-home care, and data
      suggesting a link between early care and education (ECE) participation and
      overweight/obesity, obesity prevention in ECE settings is critical. As the field
      has progressed, a number of interventions have been reviewed yet there is a need
      to summarize the data using more sophisticated analyses to answer questions on
      the effectiveness of interventions. We conducted a systematic review of obesity
      prevention interventions in center-based ECE settings published between 2010 and
      2015. Our goal was to identify promising intervention characteristics associated
      with successful behavioral and anthropometric outcomes. A rigorous search
      strategy resulted in 43 interventions that met inclusion criteria. We developed a
      coding strategy to assess intervention strength, used a validated study quality
      assessment tool, and presented detailed descriptive information about
      interventions (e.g., target behaviors, intervention strategies, and mode of
      delivery). Intervention strength was positively correlated with reporting of
      positive anthropometric outcomes for physical activity, diet, and combined
      interventions, and parent engagement components increased the strength of these
      relationships. Study quality was modestly related to percent successful healthy
      eating outcomes. Relationships between intervention strength and behavioral
      outcomes demonstrated negative relationships for all behavioral outcomes.
      Specific components of intervention strength (number of intervention strategies,
      potential impact of strategies, frequency of use, and duration of intervention)
      were correlated with some of the anthropometric and parent engagement outcomes.
      The review provided tentative evidence that multi-component, multi-level ECE
      interventions with parental engagement are most likely to be effective with
      anthropometric outcomes.

PMID- 27693296
TI  - Risk management and statistical multivariate analysis approach for design and
      optimization of satranidazole nanoparticles.
AB  - Rapidly evolving technical and regulatory landscapes of the pharmaceutical
      product development necessitates risk management with application of multivariate
      analysis using Process Analytical Technology (PAT) and Quality by Design (QbD).
      Poorly soluble, high dose drug, Satranidazole was optimally nanoprecipitated (SAT
      NP) employing principles of Formulation by Design (FbD). The potential risk
      factors influencing the critical quality attributes (CQA) of SAT-NP were
      identified using Ishikawa diagram. Plackett-Burman screening design was adopted
      to screen the eight critical formulation and process parameters influencing the
      mean particle size, zeta potential and dissolution efficiency at 30min in pH7.4
      dissolution medium. Pareto charts (individual and cumulative) revealed three most
      critical factors influencing CQA of SAT-NP viz. aqueous stabilizer (Polyvinyl
      alcohol), release modifier (Eudragit(r) S 100) and volume of aqueous phase. The
      levels of these three critical formulation attributes were optimized by FbD
      within established design space to minimize mean particle size, poly dispersity
      index, and maximize encapsulation efficiency of SAT-NP. Lenth's and Bayesian
      analysis along with mathematical modeling of results allowed identification and
      quantification of critical formulation attributes significantly active on the
      selected CQAs. The optimized SAT-NP exhibited mean particle size; 216nm,
      polydispersity index; 0.250, zeta potential; -3.75mV and encapsulation
      efficiency; 78.3%. The product was lyophilized using mannitol to form readily
      redispersible powder. X-ray diffraction analysis confirmed the conversion of
      crystalline SAT to amorphous form. In vitro release of SAT-NP in gradually pH
      changing media showed <20% release in pH1.2 and pH6.8 in 5h, while, complete
      release (>95%) in pH7.4 in next 3h, indicative of burst release after a lag time.
      This investigation demonstrated effective application of risk management and QbD
      tools in developing site-specific release SAT-NP by nanoprecipitation.

PMID- 27693298
TI  - Preparation, characterization and in-vivo evaluation of microemulsions containing
      tamoxifen citrate anti-cancer drug.
AB  - The aim of this study was to prepare and characterize a new nanocarrier for oral
      delivery of tamoxifen citrate (TMC) as a lipophilic oral administrated drug. This
      drug has low oral bioavailability due to its low aqueous solubility. To enhance
      the solubility of this drug, the microemulsion system was applied in form of oil
      in-water. Sesame oil and Tween 80 were used as drug solvent oil and surfactant,
      respectively. Two different formulations were prepared for this purpose. The
      first formulation contained edible glycerin as co-surfactant and the second
      formulation contained Span 80 as a mixed surfactant. The results of
      characterization showed that the mean droplet size of drug-free samples was in
      the range of 16.64-64.62nm with a PDI value of <0.5. In a period of 6months after
      the preparation of samples, no phase sedimentation was observed, which confirmed
      the high stability of samples. TMC with a mass ratio of 1% was loaded in the
      selected samples. No significant size enlargement and drug precipitation were
      observed 6months after drug loading. In addition, the drug release profile at
      experimental environments in buffers with pH=7.4 and 5.5 showed that in the first
      24h, 85.79 and 100% of the drug were released through the first formulation and
      76.63 and 66.42% through the second formulation, respectively. The in-vivo
      results in BALB/c female mice showed that taking microemulsion form of drug
      caused a significant reduction in the growth rate of cancerous tumor and weight
      loss of the mice compared to the consumption of commercial drug tablets. The
      results confirmed that the new formulation of TMC could be useful for breast
      cancer treatment.

PMID- 27693297
TI  - Synthesis, characterization and liver targeting evaluation of self-assembled
      hyaluronic acid nanoparticles functionalized with glycyrrhetinic acid.
AB  - Recently, polymeric materials with multiple functions have drawn great attention
      as the carrier for drug delivery system design. In this study, a series of
      multifunctional drug delivery carriers, hyaluronic acid (HA)-glycyrrhetinic acid
      (GA) succinate (HSG) copolymers were synthesized via hydroxyl group modification
      of hyaluronic acid. It was shown that the HSG nanoparticles had sub-spherical
      shape, and the particle size was in the range of 152.6-260.7nm depending on GA
      graft ratio. HSG nanoparticles presented good short term and dilution stability.
      MTT assay demonstrated all the copolymers presented no significant cytotoxicity.
      In vivo imaging analysis suggested HSG nanoparticles had superior liver targeting
      efficiency and the liver targeting capacity was GA graft ratio dependent. The
      accumulation of DiR (a lipophilic, NIR fluorescent cyanine dye)-loaded HSG-6, HSG
      12, and HSG-20 nanoparticles in liver was 1.8-, 2.1-, and 2.9-fold higher than
      that of free DiR. The binding site of GA on HA may influence liver targeting
      efficiency. These results indicated that HSG copolymers based nanoparticles are
      potential drug carrier for improved liver targeting.

PMID- 27693301
TI  - Unified and simple understanding for the evolution of conditional cooperators.
AB  - Cooperation is a mysterious phenomenon which is observed in this world. The
      potential explanation is a repeated interaction. Cooperation is established if
      individuals meet the same opponent repeatedly and cooperate conditionally.
      Previous studies have analyzed the following four as characters of conditional
      cooperators mainly. (i) niceness (i.e., when a conditional cooperator meets an
      opponent in the first place, he (she) cooperates or defects), (ii) optimism (when
      a conditional cooperator meets an opponent in the past, but he (she) did not get
      access to information about the opponent's behavior in the previous round, he
      (she) cooperates or defects), (iii) generosity (even when a conditional
      cooperator knows that an opponent defected in the previous round, he (she)
      cooperates or defects) and (iv) retaliation (a conditional cooperator cooperates
      with a cooperator with a higher probability than with a defector). Previous works
      deal with these four characters mainly. However, these four characters basically
      have been regarded as distinct topics and unified understanding has not been done
      fully. Here we, by studying the iterated prisoner's dilemma game (in particular,
      additive games) and using evolutionarily stable strategy (ESS) analysis, find
      that when retaliation is large, the condition under which conditional cooperators
      are stable against the invasion by an unconditional defector is loose, while none
      of "niceness", "optimism", and "generosity" makes impact on the condition under
      which conditional cooperators are stable against an invasion by an unconditional
      defector. Furthermore, we show that we can understand "niceness", "optimism", and
      "generosity" uniformly by using one parameter indicating "cooperative", and when
      the conditional cooperators have large "retaliation" enough to resist an invasion
      by an unconditional defector, natural selection favors more "cooperative"
      conditional cooperators to invade the resident conditional cooperative strategy.
      Moreover, we show that these results are robust even when taking the existence of
      mistakes in behavior into consideration.

PMID- 27693299
TI  - IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK
      prediction success part 3: Identifying gaps in system parameters by analysing In
      Silico performance across different compound classes.
AB  - Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp(r)
      Simulator, and GastroPlusTM) were evaluated as part of the Innovative Medicine
      Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom
      up" anticipation of human pharmacokinetics. After data analysis of the predicted
      vs. measured pharmacokinetics parameters, it was found that oral bioavailability
      (Foral) was underpredicted for compounds with low permeability, suggesting
      improper estimates of intestinal surface area, colonic absorption and/or lack of
      intestinal transporter information. Foral was also underpredicted for acidic
      compounds, suggesting overestimation of impact of ionisation on permeation, lack
      of information on intestinal transporters, or underestimation of solubilisation
      of weak acids due to less than optimal intestinal model pH settings or
      underestimation of bile micelle contribution. Foral was overpredicted for weak
      bases, suggesting inadequate models for precipitation or lack of in vitro
      precipitation information to build informed models. Relative bioavailability was
      underpredicted for both high logP compounds as well as poorly water-soluble
      compounds, suggesting inadequate models for solubility/dissolution,
      underperforming bile enhancement models and/or lack of biorelevant solubility
      measurements. These results indicate areas for improvement in model software,
      modelling approaches, and generation of applicable input data. However, caution
      is required when interpreting the impact of drug-specific properties in this
      exercise, as the availability of input parameters was heterogeneous and highly
      variable, and the modellers generally used the data "as is" in this blinded
      bottom-up prediction approach.

PMID- 27693300
TI  - A Comparison of Aerosolization and Homogenization Techniques for Production of
      Alginate Microparticles for Delivery of Corticosteroids to the Colon.
AB  - Alginate microparticles incorporating hydrocortisone hemisuccinate were produced
      by aerosolization and homogenization methods to investigate their potential for
      colonic drug delivery. Microparticle stabilization was achieved by CaCl2
      crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by
      diffusion into blank microparticles or by direct encapsulation. Homogenization
      method produced smaller microparticles (45-50 MUm), compared to aerosolization
      (65-90 MUm). High drug loadings (40% wt/wt) were obtained for diffusion-loaded
      aerosolized microparticles. Aerosolized microparticles suppressed drug release in
      simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) prior to drug
      release in simulated colonic fluid (SCF) to a higher extent than homogenized
      microparticles. Microparticles prepared using aerosolization or homogenization (1
      M CaCl2, diffusion loaded) released 5% and 17% of drug content after 2 h in SGF
      and 4 h in SIF, respectively, and 75% after 12 h in SCF. Thus, aerosolization and
      homogenization techniques show potential for producing alginate microparticles
      for colonic drug delivery in the treatment of inflammatory bowel disease.

PMID- 27693302
TI  - A new parametric method to smooth time-series data of metabolites in metabolic
      networks.
AB  - Mathematical modeling of large-scale metabolic networks usually requires
      smoothing of metabolite time-series data to account for measurement or biological
      errors. Accordingly, the accuracy of smoothing curves strongly affects the
      subsequent estimation of model parameters. Here, an efficient parametric method
      is proposed for smoothing metabolite time-series data, and its performance is
      evaluated. To simplify parameter estimation, the method uses S-system-type
      equations with simple power law-type efflux terms. Iterative calculation using
      this method was found to readily converge, because parameters are estimated
      stepwise. Importantly, smoothing curves are determined so that metabolite
      concentrations satisfy mass balances. Furthermore, the slopes of smoothing curves
      are useful in estimating parameters, because they are probably close to their
      true behaviors regardless of errors that may be present in the actual data.
      Finally, calculations for each differential equation were found to converge in
      much less than one second if initial parameters are set at appropriate (guessed)
      values.

PMID- 27693303
TI  - Mathematical analysis and validation of an exactly solvable model for upstream
      migration of fish schools in one-dimensional rivers.
AB  - Upstream migration of fish schools in 1-D rivers as an optimal control problem is
      formulated where their swimming velocity and the horizontal oblateness are taken
      as control variables. The objective function to be maximized through a migration
      process consists of the biological and ecological profit to be gained at the
      upstream-end of a river, energetic cost of swimming against the flow, and
      conceptual cost of forming a school. Under simplified conditions where the flow
      is uniform in both space and time and the profit to be gained at the goal of
      migration is sufficiently large, the optimal control variables are determined
      from a system of algebraic equations that can be solved in a cascading manner.
      Mathematical analysis of the system reveals that the optimal controls are
      uniquely found and the model is exactly solvable under certain conditions on the
      functions and parameters, which turn out to be realistic and actually satisfied
      in experimental fish migration. Identification results of the functional shapes
      of the functions and the parameters with experimentally observed data of swimming
      schools of Plecoglossus altivelis (Ayu) validate the present mathematical model
      from both qualitative and quantitative viewpoints. The present model thus turns
      out to be consistent with the reality, showing its potential applicability to
      assessing fish migration in applications.

PMID- 27693304
TI  - Evaluation of antimicrobial, cytotoxic, and hemolytic activities from venom of
      the spider Lasiodora sp.
AB  - This study characterized the protein/peptide profile of venom isolated from the
      spider Lasiodora sp. (Mygalomorphae, Theraphosidae) found in northeastern Brazil
      and determined its antimicrobial activity, toxicity against human cells, and
      hemolytic activity. Protein concentration of the Lasiodora sp. venom was 4.53 +/-
      0.38 mg/mL. SDS-PAGE showed proteins with molecular masses up to 75 kDa, some of
      which contained disulfide bridges. RP-HPLC analysis separate at least 12 peaks
      that were identified by mass spectrometry as peptides U1-theraphotoxin-Lp1a
      (lasiotoxin-1), U1-theraphotoxin-Lp1c (lasiotoxin-3), U3-theraphotoxin-Lsp1a
      (LTx5), and omega-theraphotoxin-Asp3a as well as the proteins phospholipase A2
      (PLA2) and hyaluronidase. The crude venom exhibited bactericidal effect against
      Aeromonas sp., Bacillus subtilis, and Micrococcus luteus and fungicidal effect
      against Candida parapsilosis and Candida albicans. In addition, the venom exerted
      bacteriostatic effect against Klebsiella pneumoniae, Pseudomonas aeruginosa, and
      Staphylococcus aureus and fungistatic effect against Candida tropicalis and
      Candida krusei. The minimum inhibitory (MIC), minimum bactericidal (MBC), and
      minimum fungicidal (MFC) concentrations ranged from 3.9 to 500 MUg/mL. The
      Lasiodora sp. venom decreased the viability of human peripheral blood mononuclear
      cells (PBMCs) by 50%-90% at concentrations of 0.1, 1, 10, and 100 MUg/mL,
      promoting apoptosis of these cells. On the other hand, the venom showed weak
      hemolytic activity against Mus musculus erythrocytes (EC50: 757 MUg/mL). In
      conclusion, the Lasiodora sp. spider venom is a rich source of antimicrobial
      agents. Future studies will focus on identifying antimicrobial agents present in
      this venom and evaluating whether these agents contribute to its cytotoxic
      effects against PBMCs.

PMID- 27693305
TI  - Inability to detect free cylindrospermopsin in spiked aquatic organism extracts
      plausibly suggests protein binding.
AB  - Even though the frequency and prevalence of cylindrospermopsin producing
      cyanobacteria are increasing, several publications have reported the absence of
      free cylindrospermopsin bioaccumulation in aquatic food chains.
      Cylindrospermopsin modification by protein binding has been suggested, however,
      only one publication has investigated this with eukaryotic reticulocyte lysate
      and concluded that cylindrospermopsin binds non-covalently to soluble proteins
      larger than 100 kDa associated with eukaryotic translation. With this as the
      extent of knowledge regarding cylindrospermopsin binding, the present study aimed
      to determine whether cylindrospermopsin binding also occurred with other
      proteins. In the present study, proteins from various organisms were extracted,
      incubated with cylindrospermopsin, and the amount of free cylindrospermopsin was
      determined by liquid chromatography tandem mass spectroscopy. Additionally,
      cylindrospermopsin binding to various ammonium sulfate precipitation fractions of
      Egeria densa protein, as well as with selected amino acids was investigated. We
      find that the percentage of free cylindrospermopsin varied with exposure to
      various animal and plant proteins as well as with various fractions of proteins
      but found no binding with single amino acids.

PMID- 27693306
TI  - Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular
      Polysaccharides with Anti-inflammatory Properties.
AB  - Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate
      T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells
      (Tregs). However, only a few diverse bacteria are known to modulate the host
      immune system via ZPS. We present a genomic screen for bacteria encoding ZPS
      molecules. We identify diverse host-associated bacteria, including commensals and
      pathogens with known anti-inflammatory properties, with the capacity to produce
      ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing
      bacteria induce significantly greater IL-10 production and higher proportions of
      Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of
      Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was
      genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but
      not a close relative lacking a putative ZPS, attenuated experimental colitis in
      mice. Collectively, this screen identifies bacterial strains that may use ZPSs to
      interact with the host as well as those with potential probiotic properties.

PMID- 27693307
TI  - Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on
      Individualized Features of the Resident Microbiome.
AB  - Live bacteria (such as probiotics) have long been used to modulate gut microbiota
      and human physiology, but their colonization is mostly transient. Conceptual
      understanding of the ecological principles as they apply to exogenously
      introduced microbes in gut ecosystems is lacking. We find that, when orally
      administered to humans, Bifidobacterium longum AH1206 stably persists in the gut
      of 30% of individuals for at least 6 months without causing gastrointestinal
      symptoms or impacting the composition of the resident gut microbiota. AH1206
      engraftment was associated with low abundance of resident B. longum and
      underrepresentation of specific carbohydrate utilization genes in the pre
      treatment microbiome. Thus, phylogenetic limiting and resource availability are
      two factors that control the niche opportunity for AH1206 colonization. These
      findings suggest that bacterial species and functional genes absent in the gut
      microbiome of individual humans can be reestablished, providing opportunities for
      precise and personalized microbiome reconstitution.

PMID- 27693308
TI  - Zika Virus Infection Induces Cranial Neural Crest Cells to Produce Cytokines at
      Levels Detrimental for Neurogenesis.
AB  - Zika virus (ZIKV) infection during pregnancy is linked to microcephaly, which is
      attributed to infection of developing brain structures. ZIKV infects neural
      progenitor cells in vitro, though its effects on other developmentally relevant
      stem cell populations, including cranial neural crest cells (CNCCs), have not
      been assessed. CNCCs give rise to most cranial bones and exert paracrine effects
      on the developing brain. Here, we report that CNCCs are productively infected by
      ZIKV, but not by the related dengue virus. ZIKV-infected CNCCs undergo limited
      apoptosis but secrete cytokines that promote death and drive aberrant
      differentiation of neural progenitor cultures. Addition of two such cytokines,
      LIF or VEGF, at levels comparable to those secreted by ZIKV-infected CNCCs is
      sufficient to recapitulate premature neuronal differentiation and apoptotic death
      of neural progenitors. Thus, our results suggest that CNCC infection by ZIKV may
      contribute to associated embryopathies through signaling crosstalk between
      developing face and brain structures.

PMID- 27693309
TI  - Cryo-FIB-SEM serial milling and block face imaging: Large volume structural
      analysis of biological tissues preserved close to their native state.
AB  - Many important biological questions can be addressed by studying in 3D large
      volumes of intact, cryo fixed hydrated tissues (?10,000MUm3) at high resolution
      (5-20nm). This can be achieved using serial FIB milling and block face surface
      imaging under cryo conditions. Here we demonstrate the unique potential of the
      cryo-FIB-SEM approach using two extensively studied model systems; sea urchin
      embryos and the tail fin of zebrafish larvae. We focus in particular on the
      environment of mineral deposition sites. The cellular organelles, including
      mitochondria, Golgi, ER, nuclei and nuclear pores are made visible by the image
      contrast created by differences in surface potential of different biochemical
      components. Auto segmentation and/or volume rendering of the image stacks and 3D
      reconstruction of the skeleton and the cellular environment, provides a detailed
      view of the relative distribution in space of the tissue/cellular components, and
      thus of their interactions. Simultaneous acquisition of secondary and back
      scattered electron images adds additional information. For example, a serial view
      of the zebrafish tail reveals the presence of electron dense mineral particles
      inside mitochondrial networks extending more than 20MUm in depth in the block.
      Large volume imaging using cryo FIB SEM, as demonstrated here, can contribute
      significantly to the understanding of the structures and functions of diverse
      biological tissues.

PMID- 27693310
TI  - The selective biomarker IL-8 identifies IFTA after kidney transplantation in
      blood cells.
AB  - Cellular and antibody-mediated rejection processes and also interstitial
      fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The
      search for accurate, specific and non-invasive diagnostic tools is still ongoing
      and essential for successful treatment of renal transplanted patients. Molecular
      markers in blood cells and serum may serve as diagnostic tools but studies with
      high patient numbers and differential groups are rare. We validated the potential
      value of several markers on mRNA level in blood cells and serum protein level in
      166 samples from kidney transplanted patients under standard immunosuppressive
      therapy (steroids+/-mycophenolic acid+/-calcineurin inhibitor) with stable graft
      function, urinary tract infection (UTI), IFTA, antibody-mediated rejection
      (ABMR), and T-cell-mediated rejection (TCMR) applying RT-PCR and ELISA. The mRNA
      expression of RANTES, granulysin, granzyme-B, IP-10, Mic-A and Interferon-gamma
      in blood cells did not distinguish specifically between the different
      pathologies. We furthermore discovered that the mRNA expression of the chemokine
      IL-8 is significantly lower in samples from IFTA patients than in samples from
      patients with stable graft function (p<0.001), ABMR (p<0.001), Borderline (BL)
      TCMR (p<0.001), tubulo-interstitial TCMR (p<0.001) and vascular TCMR (p<0.01),
      but not with UTI. Serum protein concentrations of granzyme-B, Interferon-gamma
      and IL-8 did not differ between the patient groups, RANTES concentration was
      significantly different when comparing UTI and ABMR (p<0.01), whereas granulysin,
      Mic-A and IP-10 measurement differentiated ongoing rejection or IFTA processes
      from stable graft function but not from each other. The measurement of IL-8 mRNA
      in blood cells distinguishes clearly between IFTA and other complication after
      kidney transplantation and could easily be used as diagnostic tool in the clinic.

PMID- 27693311
TI  - [Tubulo-papillary apocrine adenoma in association with syringocystadenoma
      papilliferum].
AB  - Tubulo-papillary apocrine adenoma (TAA) is a very rare sweat gland tumor. TAA in
      association with syringocystadenoma papilliferum (SCP) is exceptional. A 2-year
      old Tunisian child developed a mixed tumor on the scalp: TAA in association with
      SCP. Histologically, the tumor consisted of dilated duct-like areas with some
      apocrine gland-like areas. The superficial part of the tumor was connected to the
      epidermis and showed the characteristics of SCP. The characteristics and
      differences in histopathologic and immunohistochemical findings in this mixed
      tumor are described.

PMID- 27693312
TI  - The aging face.
AB  - Advancements in technology and medicine have led to a greater life expectancy and
      a corresponding increased interest in the mechanisms and prevention of aging.
      Because of its central role in human perception of age and emotion, the aging
      face generates a high demand for understanding the etiology of senescence-related
      changes. There are effective nonsurgical and surgical methods available for those
      seeking functional or cosmetic facial rejuvenation.

PMID- 27693313
TI  - A cell-based biosensor for nanomaterials cytotoxicity assessment in three
      dimensional cell culture.
AB  - Nanoparticles (NPs) are widely used in consumer and medicinal products. The high
      prevalence of nanoparticles in the environment raises concerns regarding their
      effects on human health, but there is limited knowledge about how NPs interact
      with cells or tissues. Because the European Union has called for a substantial
      reduction of animal experiments for scientific purposes (Directive 2010/63),
      increased efforts are required to develop in vitro models to evaluate potentially
      hazardous agents. Here, we describe a new cell-based biosensor for the evaluation
      of NPs cytotoxicity. The new biosensor is based on transgenic human
      hepatoblastoma cells (HepG2) that express a secreted form of alkaline phosphatase
      (SEAP) as a reporter protein whose expression is induced upon activation of a
      stress response pathway controlled by the transcription regulator nuclear factor
      kappaB (NF-kappaB). The NF-kappaB_HepG2 sensor cells were cultured in a Matrigel
      based three dimensional environment to simulate the in vivo situation. The new
      biosensor cells offer the advantage of generating fast and reproducible readout
      at lower concentrations and shorter incubation time than conventional viability
      assays, avoid possible interaction between nanomaterials and assay compounds,
      therefore, minimize generation of false positive or negative results and indicate
      mechanism of toxicity through NF-kappaB signaling.

PMID- 27693314
TI  - Select putative neurodevelopmental toxins modify SNAP-25 expression in primary
      cultures of rat cerebellar granule cells.
AB  - A presynaptic protein SNAP-25 belonging to SNARE complex which is instrumental in
      intracellular vesicular trafficking and exocytosis, has been implicated in
      hyperactivity and cognitive abilities in some neuropsychiatric disorders. The
      unclear etiology of the behavior disrupting neurodevelopmental disabilities in
      addition to genetic causes most likely involves environmental factors. The aim of
      this in vitro study was to test if various suspected developmental neurotoxins
      can alter SNAP-25 mRNA and protein expression in neurons. Real-time PCR and
      Western blotting analyses were used to assess SNAP-25 mRNA and protein levels in
      primary cultures of rat cerebellar granule cells (CGCs). The test substances:
      tetrabromobisphenol-A (TBBPA), thimerosal (TH), silver nanoparticles (NAg),
      valproic acid (VPA) and thalidomide (THAL), were administered to CGC cultures at
      subtoxic concentrations for 24h. The results demonstrated that SNAP-25 mRNA
      levels were increased by 49 and 66% by TBBPA and THAL, respectively, whereas VPA
      and NAg reduced these levels to 48 and 64% of the control, respectively. The SNAP
      25 protein content in CGCs was increased by 79% by TBBPA, 25% by THAL and 21% by
      NAg; VPA and TH reduced these levels to 73 and 69% of the control, respectively.
      The variety of changes in SNAP-25 expression on mRNA and protein level suggests
      the diversity of the mechanism of action of the test substances. This initial
      study provided no data on concentration-effect relations and on functional
      changes in CGCs. However it is the first to demonstrate the effect of different
      compounds that are suspected of causing neurodevelopmental disabilities on SNAP
      25 expression. These results suggest that this protein may be a common target for
      not only inherited but also environmental modifications linked to behavioral
      deficits in neurodevelopmental disabilities.

PMID- 27693315
TI  - Evaluation of tetrabromobisphenol A effects on human glucocorticoid and androgen
      receptors: A comparison of results from human- with yeast-based in vitro assays.
AB  - The incidence of immune-related diseases increased over the last years in
      industrialized countries, suggesting a contribution of environmental factors.
      Impaired glucocorticoid action has been associated with immune disorders. Thus,
      there is an increasing interest to identify chemicals disrupting glucocorticoid
      action. The widely used flame retardant tetrabromobisphenol A (TBBPA) was
      reported earlier to potently inhibit glucocorticoid receptor (GR) and moderately
      androgen receptor (AR) activity in yeast-based reporter gene assays. To further
      characterize possible GR disrupting effects of TBBPA, transactivation experiments
      using a human HEK-293 cell-based reporter gene assay and cell-free receptor
      binding experiments were performed in the present study. Both, transactivation
      and GR binding experiments failed to detect any activity of TBBPA on GR function.
      Molecular docking calculations supported this observation. Additionally, the
      current study could confirm the antiandrogenic activity of TBBPA seen in the
      yeast assay, although the effect was an order of magnitude less pronounced in the
      HEK-293 cell-based system. In conclusion, TBBPA does not directly affect GR
      function and, considering its rapid metabolism and low concentrations found in
      humans, it is unlikely to cause adverse effects by acting through AR. This study
      emphasizes the use of cell-free assays in combination with cell-based assays for
      the in vitro evaluation of endocrine disrupting chemicals.

PMID- 27693316
TI  - Selective scavenging of intra-mitochondrial superoxide corrects diclofenac
      induced mitochondrial dysfunction and gastric injury: A novel gastroprotective
      mechanism independent of gastric acid suppression.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple
      inflammatory diseases and pain but severe gastric mucosal damage is the worst
      outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially
      targeted superoxide (O2-) scavenger protected as well as healed gastric injury
      induced by diclofenac (DCF), the most commonly used NSAID. Common existing
      therapy against gastric injury involves suppression of gastric acid secretion by
      proton pump inhibitors and histamine H2 receptor antagonists; however, dyspepsia,
      vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks
      of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid
      secretion but offered gastroprotection by preventing DCF-induced generation of O2
      due to mitochondrial respiratory chain failure and by preventing mitochondrial
      oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF
      stimulated reduced fatty acid oxidation, mitochondrial depolarization and
      bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of
      mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling
      through NF-kappaB by DCF. Furthermore, mitoTEMPO when administered in rats with
      preformed gastric lesions expedited the healing of gastric injury and the healed
      stomach exhibited its normal physiology as evident from gastric acid and pepsin
      secretions under basal or stimulated conditions. Thus, in contrast to the
      existing antiulcer drugs, mitochondrially targeted O2- scavengers like mitoTEMPO
      may represent a novel class of gastroprotective molecules that does not affect
      gastric acid secretion and may be used in combination with DCF, keeping its anti
      inflammatory action intact, while reducing its gastrodamaging effects.

PMID- 27693317
TI  - Andrographolide reversed 5-FU resistance in human colorectal cancer by elevating
      BAX expression.
AB  - 5-FU is the first line therapy for colorectal cancer, however, treatment effect
      is often hampered by the development of drug resistance or toxicity at high
      doses. Andrographolide is a natural diterpenoid from Andrographis paniculata
      which has anti-bacterial, anti-antiviral and anti-inflammation activities. In the
      current study, we test the hypothesis that Andrographolide reverses 5-FU
      resistance in colorectal cancer and examine the underlying mechanism. In vitro
      and vivo studies indicated that Andrographolide treatment significantly re
      sensitizes HCT116/5-FUR cells (HCT116 cells which are 5-FU resistant) to
      cytotoxicity of 5-FU. Mechanism analysis showed that Andrographolide/5-FU co
      treatment elevated apoptosis level of HCT116/5-FUR cells with highly increased
      level of BAX. By using biotin-Andrographolide pull down and cellular thermal
      shift assay, we found out that Andrographolide can directly target to BAX.
      Andrographolide-BAX interaction prevented BAX degradation, enhancing mitochondria
      mediated apoptosis thus reversed 5-FU resistance while BAX silence diminished
      this effect. Further, by analyzing patient samples who received 5-FU involved
      chemotherapy, we found that expression level of BAX is correlated with PFS. Our
      results here provide a novel combination treatment strategy, especially for
      patients with 5-FU-resistant tumors expressing low level of BAX. Meanwhile, we
      also proposed that BAX expression may be a predicted and prognosis marker of 5-FU
      involved chemotherapy.

PMID- 27693318
TI  - Accuracies of fecal calprotectin, lactoferrin, M2-pyruvate kinase, neopterin and
      zonulin to predict the response to infliximab in ulcerative colitis.
AB  - BACKGROUND: Fecal markers might predict the response to anti-TNFalpha in
      ulcerative colitis (UC). AIMS: To compare the performance of fecal calprotectin
      (fCal), lactoferrin (fLact), M2-PK (fM2-PK), neopterin (fNeo), and zonulin (fZon)
      to predict the response to therapy in active UC patients. METHODS: Disease
      activity from 31 consecutive patients with an active UC, treated with infliximab
      (IFX) was assessed by the Mayo score at baseline and at week 14 and by the
      partial Mayo score at W52 and stool samples collected for fecal marker
      measurements at W0, W2, and W14. RESULTS: At W14, 19 patients (61%) were
      responders to IFX induction. The median levels of fCal, fLact and fM2-PK drop
      dramatically from baseline to W14 in clinical responders. At W2, fM2-PK, fLact
      and fCal levels predicted accurately the response to IFX induction. At W14,
      fLact, fCal, and fM2-PK were individually reliable markers to predict sustained
      response at W52. The performances of fNeo and fZon were weaker in this setting.
      CONCLUSIONS: The performance of fM2-PK at W2 to predict response to induction
      therapy with IFX was superior to that of fLact and fCal, whereas monitoring fLact
      was the best tool to predict adequately the course of the disease at one year
      under maintenance IFX in UC.

PMID- 27693319
TI  - CRISPRi engineering E. coli for morphology diversification.
AB  - Microbial morphology engineering has recently become interesting for
      biotechnology. Genes ftsZ and mreB encoding proteins of bacterial fission ring
      and skeletons, respectively, are essential for cell growth, they both are the
      most important genes keeping the bacterial shapes including the cell length and
      width, respectively. Clustered regularly interspaced short palindromic repeats
      interference, abbreviated as CRISPRi, was for the first time used in this study
      to regulate expression intensities of ftsZ or/and mreB in E. coli. Five sgRNAs
      associated with CRISPRi were designed and synthesized, respectively, to target
      five various locations on genes ftsZ or mreB encoded in the E. coli chromosome,
      resulting in various reduced expression levels of ftsZ or/and mreB, respectively,
      forming elongated or/and fatter cells. Repressions on gene expressions of ftsZ
      or/and mreB could be further intensified by combining various sgRNAs together. It
      was found that the stronger the repression on genes ftsZ or/and mreB, the longer
      the E. coli fibers, and the larger the E. coli cells. Combined repressions on
      expressions of ftsZ and mreB generated long and larger E. coli with diverse
      morphologies including various sizes of gourds, bars, coccus, spindles, multi
      angles and ellipsoids. In all cases, accumulations of intracellular biopolyester
      polyhydroxybutyrate (PHB) were in direct proportional to the intracellular
      volumes, ranging from 40% to 80% PHB in bacterial cell dry weights, depending on
      the cell volumes increases by the above CRISPRi applications.

PMID- 27693320
TI  - CRISPR-Cas9 for the genome engineering of cyanobacteria and succinate production.
AB  - Cyanobacteria hold promise as a cell factory for producing biofuels and bio
      derived chemicals, but genome engineering of cyanobacteria such as Synechococcus
      elongatus PCC 7942 poses challenges because of their oligoploidy nature and long
      term instability of the introduced gene. CRISPR-Cas9 is a newly developed RNA
      guided genome editing system, yet its application for cyanobacteria engineering
      has yet to be reported. Here we demonstrated that CRISPR-Cas9 system can
      effectively trigger programmable double strand break (DSB) at the chromosome of
      PCC 7942 and provoke cell death. With the co-transformation of template plasmid
      harboring the gene cassette and flanking homology arms, CRISPR-Cas9-mediated DSB
      enabled precise gene integration, ameliorated the homologous recombination
      efficiency and allowed the use of lower amount of template DNA and shorter
      homology arms. The CRISPR-Cas9-induced cell death imposed selective pressure and
      enhanced the chance of concomitant integration of gene cassettes into all
      chromosomes of PCC 7942, hence accelerating the process of obtaining homogeneous
      and stable recombinant strains. We further explored the feasibility of
      engineering cyanobacteria by CRISPR-Cas9-assisted simultaneous glgc knock-out and
      gltA/ppc knock-in, which improved the succinate titer to 435.0+/-35.0MUg/L, an
      ~11-fold increase when compared with that of the wild-type cells. These data
      altogether justify the use of CRISPR-Cas9 for genome engineering and manipulation
      of metabolic pathways in cyanobacteria.

PMID- 27693321
TI  - What Is A Normal Intestinal Mucosa?

PMID- 27693322
TI  - Focal and Local: Ectopic Lymphoid Structures and Aggregates of Myeloid and Other
      Immune Cells in Liver.

PMID- 27693324
TI  - Long non-coding RNA TUG1 regulates ovarian cancer proliferation and metastasis
      via affecting epithelial-mesenchymal transition.
AB  - Ovarian cancer is the fifth leading cause of cancer-related death in women
      worldwide, and recent studies have highlighted the role of long non-coding RNAs
      (lncRNAs) in cancer development. However, the role of lncRNAs in ovarian cancer
      is largely unclear. In this study, we focused on the taurine up-regulated gene 1
      (TUG1) and examined its molecular mechanism in ovarian cancer. Here, we reported
      that TUG1 was up-regulated in ovarian cancer tissues and ovarian cancer cells,
      and TUG1 expression was positively correlated with tumor grade and FIGO stage. In
      vitro functional assays (CCK-8 assay, colony formation assay, and cell invasion
      assay) revealed that knock-down of TUG1 by small RNA inference significantly
      inhibited cell proliferation, colony formation and cell invasion in ovarian
      cancer cells. Further experiment showed that knock-down of TUG1 induced cell
      apoptosis and altered the protein expression levels of apoptosis-related
      mediators in ovarian cancer cells. More importantly, knock-down of TUG1 also
      reversed epithelial-mesenchymal transition in ovarian cancer. In summary, our
      results suggest that knock-down of TUG1 may represent a novel therapeutic
      strategy for the treatment of ovarian cancer.

PMID- 27693325
TI  - Adverse tissue reactions after total hip arthroplasty.
AB  - Hip arthroplasty is commonly performed on patients with debilitating hip disease
      to relieve symptoms and improve quality of life. Generally, long-term success
      rates are excellent. However, a subset of patients requires revision due to
      prosthesis failure. A wide array of microscopic findings can be seen in
      surrounding tissues and many of the findings are etiologically nonspecific. The
      aim of this review is to discuss the etiologies and accompanying adverse tissue
      reactions seen with prosthesis failure, including the findings seen in aseptic
      lymphocyte-dominated vasculitis-associated lesion. Aseptic lymphocyte-dominated
      vasculitis-associated lesion is an important diagnostic consideration as its
      proposed pathogenesis is a type VI hypersensitivity response to metal ions. In
      addition, we also propose a diagnostic algorithm that incorporates clinical and
      histopathologic findings to suggest an etiologic cause. This proposed algorithm
      may be clinically useful as, to date, there is no consensus on nomenclature.

PMID- 27693323
TI  - Interleukin 1beta Mediates Intestinal Inflammation in Mice and Patients With
      Interleukin 10 Receptor Deficiency.
AB  - Interleukin 10 receptor (IL10R)-deficient mice develop spontaneous colitis and,
      similarly, patients with loss-of-function mutations in IL10R develop severe
      infant-onset inflammatory bowel disease. Loss of IL10R signaling in mouse and
      human macrophages is associated with increased production of interleukin 1beta.
      We demonstrated that innate immune production of IL1beta mediates colitis in
      IL10R-deficient mice. Transfer of Il1r1-/- CD4+ T cells into Rag1-/-/Il10rb-/-
      mice reduced the severity of their colitis (compared to mice that received CD4+ T
      cells that express IL1R), accompanied by decreased production of interferon
      gamma, tumor necrosis factor-alpha, and IL17A. In macrophages from mice without
      disruption of IL10R signaling or from healthy humans (controls), incubation with
      IL10 reduced canonical activation of the inflammasome and production of IL1beta
      through transcriptional and post-translational regulation of NLRP3.
      Lipopolysaccharide and adenosine triphosphate stimulation of macrophages from
      Il10rb-/- mice or IL10R-deficient patients resulted in increased production of
      IL1beta. Moreover, in human IL10R-deficient macrophages, lipopolysaccharide
      stimulation alone triggered IL1beta secretion via non-canonical, caspase 8
      dependent activation of the inflammasome. We treated 2 IL10R-deficient patients
      with severe and treatment-refractory infant-onset inflammatory bowel disease with
      the IL1-receptor antagonist anakinra. Both patients had marked clinical,
      endoscopic, and histologic responses after 4-7 weeks. This treatment served as
      successful bridge to allogeneic hematopoietic stem cell transplantation in 1
      patient. Our findings indicate that loss of IL10 signaling leads to intestinal
      inflammation, at least in part, through increased production of IL1 by innate
      immune cells, leading to activation of CD4+ T cells. Agents that block IL1
      signaling might be used to treat patients with inflammatory bowel disease
      resulting from IL10R deficiency.

PMID- 27693327
TI  - Up-regulation of nuclear factor E2-related factor 2 (Nrf2) represses the
      replication of SVCV.
AB  - Generation of reactive oxygen species (ROS) and failure to maintain an
      appropriate redox balance contribute to viral pathogenesis. Nuclear factor E2
      related factor 2 (Nrf2) is an important transcription factor that plays a pivotal
      role in maintaining intracellular homoeostasis and coping with invasive pathogens
      by coordinately activating a series of cytoprotective genes. Previous studies
      indicated that the transcription and expression levels of Nrf2 were up-regulated
      in SVCV-infected EPC cells with the unknown mechanism(s). In this study, the
      interactions between the Nrf2-ARE signalling pathway and SVCV replication were
      investigated, which demonstrated that SVCV infection induced accumulation of ROS
      as well as protein carbonyl groups and 8-OHdG, accompanied by the up-regulation
      of Nrf2 and its downstream genes. At the same time, the activation of Nrf2 with
      D, l-sulforaphane (SFN) and CDDO-Me could repress the replication of SVCV, and
      knockdown of Nrf2 by siRNA could promote the replication of SVCV. Taken together,
      these observations indicate that the Nrf2-ARE signal pathway activates a passive
      defensive response upon SVCV infection. The conclusions presented here suggest
      that targeting the Nrf2 pathway has potential for combating SVCV infection.

PMID- 27693328
TI  - Transcriptional responses of metallothionein gene to different stress factors in
      Pacific abalone (Haliotis discus hannai).
AB  - A novel metallothionein (MT) gene from the Pacific abalone H. discus hannai was
      characterized and its mRNA expression patterns (tissue distribution,
      developmental expression and differential expression in responsive to various in
      vivo stimulatory treatments) were examined. Abalone MT shares conserved
      structural features with previously known gastropod orthologs at both genomic
      (i.e., tripartite organization) and amino acid (conserved Cys motifs) levels. The
      5'-flanking regulatory region of abalone MT gene displayed various transcription
      factor binding motifs particularly including ones related with metal regulation
      and stress/immune responses. Tissue distribution and basal expression patterns of
      MT mRNAs indicated a potential association between ovarian MT expression and
      sexual maturation. Developmental expression pattern suggested the maternal
      contribution of MT mRNAs to embryonic and early larval developments. Abalone MT
      mRNAs could be significantly induced by various heavy metals in different tissues
      (gill, hepatopancreas, muscle and hemocyte) in a tissue- and/or metal-dependent
      fashion. In addition, the abalone MT gene was highly modulated in responsive to
      other non-metal, stimulatory treatments such as immune challenge (LPS, polyI:C
      and bacterial injections), hypoxia (decrease from normoxia 8 ppm-2 ppm), thermal
      elevation (increase from 20  degrees C to 30  degrees C), and xenobiotic exposure
      (250 ppb of 17alpha-ethynylestradiol and 0.25 ppb of 2,3,7,8
      tetrachlorodibenzodioxin) where differential expression patterns were toward
      either up- or down-regulation depending on types of stimulations and tissues
      examined. Taken together, our results highlight that MT is a multifunctional
      effector playing in wide criteria of cellular pathways especially associated with
      development and stress responses in this abalone species.

PMID- 27693329
TI  - Nonsteroidal Anti-inflammatory Drugs for Prevention of Post-ERCP Pancreatitis:
      Sooner Rather Than Later during ERCP?

PMID- 27693330
TI  - Treatment Targets in Ulcerative Colitis.

PMID- 27693326
TI  - Imaging of radicals following injury or acute stress in peripheral nerves with
      activatable fluorescent probes.
AB  - Peripheral nerve injury evokes a complex cascade of chemical reactions including
      generation of molecular radicals. Conversely, the reactions within nerve induced
      by stress are difficult to directly detect or measure to establish causality.
      Monitoring these reactions in vivo would enable deeper understanding of the
      nature of the injury and healing processes. Here, we utilized near-infrared
      fluorescence molecular probes delivered via intra-neural injection technique to
      enable live, in vivo imaging of tissue response associated with nerve injury and
      stress. These initially quenched fluorescent probes featured specific sensitivity
      to hydroxyl radicals and become fluorescent upon encountering reactive oxygen
      species (ROS). Intraneurally delivered probes demonstrated rapid activation in
      injured rat sciatic nerve but minimal activation in normal, uninjured nerve. In
      addition, these probes reported activation within sciatic nerves of living rats
      after a stress caused by a pinprick stimulus to the abdomen. This imaging
      approach was more sensitive to detecting changes within nerves due to the induced
      stress than other techniques to evaluate cellular and molecular changes.
      Specifically, neither histological analysis of the sciatic nerves, nor the
      expression of pain and stress associated genes in dorsal root ganglia could
      provide statistically significant differences between the control and stressed
      groups. Overall, the results demonstrate a novel imaging approach to measure ROS
      in addition to the impact of ROS within nerve in live animals.

PMID- 27693331
TI  - Targeting S1P Receptors, A New Mechanism of Action for Inflammatory Bowel Disease
      Therapy.

PMID- 27693332
TI  - Lymphoproliferative response after stimulation with soluble leishmania antigen
      (SLA) as a predictor of visceral leishmaniasis (VL) relapse in HIV+ patients.
AB  - The introduction of HAART resulted in the decrease of Leishmania/HIV co-infection
      cases; nevertheless, the number of relapses remains high and secondary
      prophylaxis is recommended. However, secondary prophylaxis is not necessary in
      all patients, and presents a high risk of toxicity and an elevated cost. Our aim
      was to study whether specific cellular response to Leishmania infantum (measured
      by cell proliferation response after stimulation with soluble Leishmania antigen
      (SLA)), could be a useful tool to attempt a secondary prophylaxis withdrawal. In
      June 2009 an outbreak of leishmaniasis by Leishmania infantum was declared in the
      southeast of Madrid, and since January 2013, we recruited 10 HIV+ patients that
      had been treated for visceral leishmaniasis. 6 patients had positive SLA-cell
      proliferation test. The mean CD4 cell counts of those patients with positive SLA
      were 140 cel/mm3 and 40 cel/mm3 in those with negative SLA test. 3 patients with
      positive SLA-cell proliferation test (CD4 count: 336, 307, 625) were not on
      prophylaxis, and the other 3 patients (CD4 count: 152, 189, 359) were on
      secondary prophylaxis that was withdrawn after the positive SLA-cell
      proliferation test with no posterior relapses (mean follow up 60 weeks). From the
      4 patients, which had negative SLA-cell proliferation test and continued on
      prophylaxis, 3 had positive PCR for Leishmania at the end of the follow-up and 2
      presented clinical relapses. The performance of SLA-cell proliferation test can
      be a useful tool that can permit us to try withdrawal of the prophylaxis in
      Leishmania/HIV co-infected patients with low CD4+ counts under clinical
      supervision, diminishing risk of toxicity and cost.

PMID- 27693333
TI  - Lessons from implementation of ecohealth projects in Southern Africa: A principal
      investigator's perspective.
AB  - Ecohealth projects are designed to garner ownership among all stakeholders, such
      as researchers, communities, local leadership and policy makers. Ideally, designs
      should ensure that implementation goes smoothly and that findings from studies
      benefit the stakeholders, particularly bringing changes to the communities
      researched. Paradoxically, the process is fraught with challenges associated with
      implementation. Notwithstanding these challenges, evidence from projects
      implemented in southern Africa justify the need to invest in the subject of
      ecohealth. This paper describes and discusses a principal investigator's
      experience of leading ecohealth projects in Zimbabwe between 2002 and 2005, in
      Botswana between 2010 and 2014 and in South Africa (ongoing). The discourse is
      centred on issues of project management and leadership, transdisciplinarity,
      students' involvement, data management, community engagement, dissemination of
      research findings and the role of institutions in project management and
      implementation. The paper concludes that the ecohealth approach is valuable and
      should be encouraged making the following recommendations; 1) principal
      investigators must have a good understanding of socio-ecological systems, have
      excellent project management and writing skills, 2) more than one PI should be
      involved in the day-to-day running of the project in order to avoid disruption of
      project activities in the event that the PI leaves the project before it ends, 3)
      researchers should be trained in ecohealth principles and methodologies at the
      time of building the research teams, 4) full proposals should be developed with
      active participation of communities and stakeholders in order to develop a shared
      vision, 5) involvement of postdoctoral fellows and dedicated researchers with
      postgraduate students should be encouraged to avoid situations where some
      objectives are not fully addressed because of the narrow nature of students'
      work; and 6) citizen science should be encouraged to empower communities and
      ensure that certain activities continue after project termination.

PMID- 27693334
TI  - Historical developments in children's deep brain stimulation.
AB  - BACKGROUND: Heterogeneous by the underlying pathobiology and clinical
      presentation, childhood onset dystonia is most frequently progressive, with
      related disability and limitations in functions of daily living. Consequently,
      there is an obvious need for efficient symptomatic therapies. METHODS AND
      RESULTS: Following lesional surgery to basal ganglia (BG) and thalamus, deep
      brain stimulation (DBS) is a more conservative and adjustable intervention to and
      validated for internal segment of the globus pallidus (GPi), highly efficient in
      treating isolated "primary" dystonia and associated symptoms such as subcortical
      myoclonus. The role of DBS in acquired, neurometabolic and degenerative disorders
      with dystonia deserves further exploration to confirm as an efficient and lasting
      therapy. However, the pathobiological background with distribution of the
      sequellae over the central nervous system and related clinical features, will
      limit DBS efficacy in these conditions. Cumulative arguments propose DBS in
      severe life threatening dystonic conditions called status dystonicus as first
      line therapy, irrespective of the underlying cause. There are no currently
      available validated selection criteria for DBS in pediatric dystonia. Concurrent
      targets such as subthalamic nucleus (STN) and several motor nuclei of the
      thalamus are under exploration and only little information is available in
      children. DBS programming in paediatric population was adopted from experience in
      adults. The choice of neuromodulatory DBS parameters could influence not only the
      initial therapeutic outcome of dystonic symptoms but also its maintenance over
      time and potentially the occurrence of DBS related side effects. CONCLUSION: DBS
      allows efficient symptomatic treatment of severe dystonia in children and
      advances pathophysiological knowledge about local and distributed abnormal neural
      activity over the motor cortical-subcortical networks in dystonia and other
      movement disorders.

PMID- 27693335
TI  - Investigation of the effects of vanilloids in chronic fatigue syndrome.
AB  - AIM OF THE STUDY: To assess the effectiveness of TRPV1 modulators in animal model
      of Chronic fatigue syndrome (CFS). To assess central and peripheral behavioral
      activity of TRPV1 modulators. MATERIAL AND METHODS: CFS was induced by forcing
      the rats to swim for 10min for 21 consecutive days. The rats were treated with
      capsaicin (TRPV1 agonist, 2.5mg/kg) and n-tert-butylcyclohexanol (TRPV1
      antagonist, 10mg/kg) for 21days 30min before the exposure to stress procedure.
      The behavioral consequence of CFS was measured in terms of immobility time, grip
      strength, locomotor activity, and anxiety level using Rota rod, Actophotometer,
      and Elevated plus maze model respectively. The other parameters include Plasma
      corticosterone, adrenal gland and spleen weight, complete blood count, blood urea
      niterogen (BUN), Lactate dehydrogenase (LDH), Lipid peroxidation, catalase and
      reduced glutathione (GSH). RESULTS AND DISCUSSION: TRPV1 modulators reversed
      (p<0.05) the increase in immobility period, anxiety, spleen weight, BUN and LDH
      levels, and MDA levels along with decrease in grip strength, locomotor activity,
      plasma corticosterone, adrenal gland weight, catalase, and GSH. There was also
      significant increase in total WBC count when compared with the disease control
      group. The reversal was attributed to modulation of HPA axis, oxidative stress,
      anaerobic respiration product, muscle degradation product. CONCLUSION: The
      present study reveals the effectiveness of n-tert-butylcyclohexanol and capsaicin
      against chronic fatigue syndrome. The mechanism of action can be attributed to
      inhibition of TRPV1 channel and thereby modulating pain perception,
      neuroendocrine function, oxidative stress and immune function.

PMID- 27693336
TI  - Anti-aggregation property of thymoquinone induced by copper-nanoparticles: A
      biophysical approach.
AB  - Quaternary amine of diethylaminoethyl rosin ester (QRMAE), chemically synthesized
      by rosin modified biocompatible cationic surfactant, has various biological
      applications in the field of pharmacy as well as used as food product additive.
      Here, we report biophysical insights in to the interaction mechanism of
      thymoquinone (TQ), copper nanoparticles (Cu-NPs) and QRMAE with bovine serum
      albumin (BSA) individually and also in complexes forms to determine their
      competitive binding affinity. We have also studied the aggregation-inhibition
      effects of Cu-NPs and TQ individually, as well as in complexes form in the
      presence of QRMAE surfactant which is responsible for induction of amorphous
      aggregates in BSA within hours of incubation at 65 degrees C and physiological
      pH. The formation of aggregates was established by using various spectroscopic
      methods and dye binding assay. The circular dichroism (CD) spectroscopy showed
      that QRMAE significantly altered the secondary structure of BSA. However, the
      presence of TQ and Cu-NPs restricted the aggregation process which was observed
      to be more efficient when TQ and Cu-NPs were present together. This study
      provides very significant competitive binding results of QRMAE, Cu-NPs, TQ and
      protein aggregation behavior at higher temperature which was induced by rosin
      surfactant QRMAE, and protein aggregation process was inhibited by Cu-NPs, TQ
      individually and together. Therefore, our finding suggested that rosin surfactant
      QRMAE has high propensity to induce amorphous aggregation in BSA which was
      favored at elevated temperature and higher concentration of the protein. When BSA
      QRMAE sample was incubated in the presence Cu-NPs under similar condition, the
      aggregation propensity reduced, and drastically inhibited by TQ and Cu-NPs
      together.

PMID- 27693337
TI  - Immobilization of glucoamylase on triazine-functionalized Fe3O4/graphene oxide
      nanocomposite: Improved stability and reusability.
AB  - Immobilization of an enzyme can enhance its catalytic activity, depending on the
      properties of the enzyme and the matrix. Graphene oxide is a nontoxic material
      and selective modulator for enzyme activity and is also a thermostable molecule
      that is important in large-scale nanostructure sheet applications. Herein, we
      have successfully developed a strategy for preparing a nanocomposite for enzyme
      immobilization model with high loading capacity. Nanostructures of hybrid
      graphene oxide-Fe3O4-cyanuric chloride (GO/MNP-CC) have adjustable surface
      chemistry that is an excellent candidate for covalent immobilization of enzymes.
      The morphology, structure and properties of GO/MNP-CC nanocomposite were
      investigated through different analytical tools. Glucoamylase, an important
      enzyme in industrial food products, was immobilized on GO/MNP-CC and exhibited
      excellent catalytic activity at pH 6.5 and 60 degrees C. The results of this
      study indicated that the catalytic activity, reusability and stability of
      immobilized enzyme have been obviously improved compared to the free enzyme. The
      apparent Km and numax for free and immobilized glucoamylase were also determined.
      These properties make them a good candidate to improve the practicality and
      further the development of the capacity enzyme attachment. Thus, the synthesized
      matrix has the potential for practical applications in other and binary enzyme
      immobilization and would have a wide prospect for their applications in bio
      industry and biosensing.

PMID- 27693338
TI  - Targeted delivery of doxorubicin to breast cancer cells by magnetic LHRH chitosan
      bioconjugated nanoparticles.
AB  - The novel dual targeted nanoparticles loaded with doxorubicin (DOX) and magnetic
      nanoparticles (MNPs) were prepared for treatment of breast cancer. Nanoparticles
      were produced by a layer-by-layer technique and functionalized with a
      bioconjugate of chitosan-poly(methyl vinyl ether maleic acid)(PMVMA)-LHRH to
      target LHRH receptors. The successful production of chitosan-PMVMA copolymer and
      its conjugation to LHRH was confirmed by FTIR and 1HNMR spectroscopy. Capillary
      electrophoresis analysis showed 72.51% LHRH conjugation efficiency. Transmission
      electron microscopy and thermogravimetric analysis showed the entrapment of the
      MNPs in the core of the nanoparticles and vibrating sample magnetometery
      confirmed their paramagnetic properties. The iron content of nanoparticles
      determined by inductively coupled plasma optical emission spectrometry showed to
      be between 3.5-84%. Particle size, zeta potential, drug entrapment and release
      efficiency of the nanoparticles were 88.1-182.6nm, 10-30mV, 62.3-87.6% and 79.8
      83.4%, respectively. No significant protein binding was seen by nanoparticles.
      The MTT assay showed in LHRH positive cells of MCF-7 the IC50 of the drug reduced
      to about 2 fold compared to the free drug. By saturation of LHRH receptors the
      viable MCF7 cells increased significantly after exposure with the targeted
      nanoparticles. Therefore, the cellular uptake of the nanoparticles might be done
      by active endocytosis through the LHRH receptors.

PMID- 27693339
TI  - Chitosan/Mimosa tenuiflora films as potential cellular patch for skin
      regeneration.
AB  - Bio-composites films were prepared by casting and drying of aqueous solutions
      containing different weight ratios of chitosan and bark of Mimosa tenuiflora. The
      physico-chemical and functional properties of the films were characterized by
      scanning electron microscopy, dynamical mechanical analysis, wettability,
      cytotoxicity and in vitro antibacterial activities. The morphology studies
      confirmed that the presence of Mimosa tenuiflora change the surface of films.
      Moreover, the incorporation of Mimosa tenuiflora improved the thermal stability
      of the films, as it was indicated by the changes in the glass temperatures
      obtained. Water-uptake ability changed in relation to polymeric composition of
      film. This property increased by the addition of Mimosa tenuiflora to the film.
      Improved antibacterial properties were measured against Escherichia Coli and
      Micrococcus lysodeikticus or luteus. Finally, cytotoxicity was studied by MTT
      assay and the films were non-toxic. These preliminary results provide a cheap way
      to prepare chitosan/Mimosa tenuiflora films for wound healing and skin
      regeneration.

PMID- 27693340
TI  - Effect of testosterone and its aliphatic and aromatic dimers on DNA morphology.
AB  - Conjugation of DNA with testosterone and it aliphatic dimer (alip) and aromatic
      dimer (arom) was investigated in aqueous solution at pH 7.4. Multiple
      spectroscopic methods, transmission electron microscopy (TEM) and molecular
      modeling were used to characterize steroid-DNA binding and DNA morphology.
      Spectroscopic analysis showed that testosterone binds DNA via A7, A16, A17, T8,
      T15 and T18 nucleobases with overall binding constants Ktest-DNA=1.8 (+/
      0.4)*104M-1, Ktest-dimeralip-DNA=5.7 (+/-0.7)*104M-1 and Ktest-dimer-arom-DNA=7.3
      (+/-0.9)*104M-1. The binding affinity increases in this order: testosterone dimer
      aromatic>testosterone dimer-aliphatic>testosterone. The steroid loading efficacy
      was 40-50%. Transmission electron microscopy showed major changes in DNA
      morphology as testosterone-DNA interaction occurred with increase in the diameter
      of the DNA aggregate, indicating encapsulation of testosterone by DNA. Modeling
      showed the presence of several nucleobases attached to testosterone with the free
      binding energy of -4.93Kcal/mol.

PMID- 27693341
TI  - Differences in conformational stability of the two alpha domains of the disease
      associated and non-disease-associated subtypes of HLA-B27.
AB  - The MHC Class I molecule, HLA-B27, is strongly linked with development of the
      inflammatory arthritic disease, ankylosing spondylitis (AS); whereas the B*2705
      subtype shows strong association, B*2709 is not associated with disease, even
      though the two subtypes differ in only a single residue at position 116.
      Currently, attention is focused on the misfolding propensities of these two
      subtypes, including studies of disulfide-linked dimers and non-covalently formed
      high molecular weight (HMW) aggregates. Using mutants retaining only a single
      cysteine at positions C67 or C164, and using a cysteine-reactive, environment
      sensitive, fluorescence probe (acrylodan), we find that within the same overall
      population of identical single-cysteine HLA-B27 molecules, there exist sub
      populations which (a) possess free cysteines which react with acrylodan, (b) form
      disulfide-linked dimers, and (c) form HMW aggregates. Further, using acrylodan
      fluorescence, we find (d) that the alpha1 and alpha2 domains unfold independently
      of each other in HMW aggregates, (e) that these two domains of B*2709 are less
      stable to chemical and thermal denaturation than the corresponding domains of
      B*2705, suggesting easier clearance of misfolded molecules in the former, and (f)
      C67 is much more exposed in B*2705 than in B*2709, which could potentially
      explain how B*2705 more easily forms C67-mediated disulfide-bonded dimers.

PMID- 27693342
TI  - A review on the pharmacological effects of vitexin and isovitexin.
AB  - Vitexin and isovitexin are active components of many traditional Chinese
      medicines, and were found in various medicinal plants. Vitexin (apigenin-8-C
      glucoside) has recently received increased attention due to its wide range of
      pharmacological effects, including but not limited to anti-oxidant, anti-cancer,
      anti-inflammatory, anti-hyperalgesic, and neuroprotective effects. Isovitexin
      (apigenin-6-C-glucoside), an isomer of vitexin, generally purified together with
      vitexin, also exhibits diverse biological activities. Latest research has
      suggested that vitexin and isovitexin could be potential substitute medicines for
      diversity diseases, and may be adjuvants for stubborn diseases or health
      products. This review summarized recent findings on various pharmacological
      activities and associative signalling pathways of vitexin and isovitexin to
      provide a reference for future research and clinical applications.

PMID- 27693344
TI  - Diverse relations between ABC transporters and lipids: An overview.
AB  - It was first discovered in 1992 that P-glycoprotein (Pgp, ABCB1), an ATP binding
      cassette (ABC) transporter, can transport phospholipids such as
      phosphatidylcholine, -ethanolamine and -serine as well as glucosylceramide and
      glycosphingolipids. Subsequently, many other ABC transporters were identified to
      act as lipid transporters. For substrate transport by ABC transporters, typically
      a classic, alternating access model with an ATP-dependent conformational switch
      between a high and a low affinity substrate binding site is evoked. Transport of
      small hydrophilic substrates can easily be imagined this way, as the molecule can
      in principle enter and exit the transporter in the same orientation. Lipids on
      the other hand need to undergo a 180 degrees  degree turn as they translocate
      from one membrane leaflet to the other. Lipids and lipidated molecules are highly
      diverse, so there may be various ways how to achieve their flipping and flopping.
      Nonetheless, an increase in biophysical, biochemical and structural data is
      beginning to shed some light on specific aspects of lipid transport by ABC
      transporters. In addition, there is now abundant evidence that lipids affect ABC
      transporter conformation, dynamics as well as transport and ATPase activity in
      general. In this review, we will discuss different ways in which lipids and ABC
      transporters interact and how lipid translocation may be achieved with a focus on
      the techniques used to investigate these processes. This article is part of a
      Special Issue entitled: Lipid order/lipid defects and lipid-control of protein
      activity edited by Dirk Schneider.

PMID- 27693343
TI  - Neural mechanisms of human temporal fear conditioning.
AB  - Learning the temporal relationship between a warning cue (conditioned stimulus;
      CS) and aversive threat (unconditioned stimulus; UCS) is an important aspect of
      Pavlovian conditioning. Although prior functional magnetic resonance imaging
      (fMRI) research has identified brain regions that support Pavlovian conditioning,
      it remains unclear whether these regions support time-related processes important
      for this type of associative learning. Elucidating the neural substrates of
      temporal conditioning is important for a complete understanding of the Pavlovian
      conditioning process. Therefore, the present study used a temporal Pavlovian
      conditioning procedure to investigate brain activity that mediates the formation
      of temporal associations. During fMRI, twenty-three healthy volunteers completed
      a temporal conditioning procedure and a control task that does not support
      conditioning. Specifically, during the temporal conditioning procedure, the UCS
      was presented at fixed intervals (ITI: 20s) while in the control condition the
      UCS was presented at random intervals (Average ITI: 20s, ITI Range: 6-34s). We
      observed greater skin conductance responses and expectancy of the UCS during
      fixed (i.e., temporal conditioning) relative to random (i.e., control procedure)
      interval trials. These findings demonstrate fixed trials support temporal
      conditioning, while random trials do not. During fixed interval trials, greater
      conditioned fMRI signal responses were observed within dorsolateral prefrontal
      cortex, inferior parietal lobule, inferior and middle temporal cortex,
      hippocampus, and amygdala. The current findings suggest these brain regions
      constitute a neural circuit that encodes the temporal information necessary for
      Pavlovian fear conditioning.

PMID- 27693345
TI  - Biosurfactants and surfactants interacting with membranes and proteins: Same but
      different?
AB  - Biosurfactants (BS) are surface-active molecules produced by microorganisms. For
      several decades they have attracted interest as promising alternatives to current
      petroleum-based surfactants. Aside from their green profile, they have remarkably
      low critical micelle concentrations, reduce the air/water surface tension to very
      low levels and are excellent emulsifiers, all of which make them comparable or
      superior to their synthetic counterparts. These remarkable physical properties
      derive from their more complex chemical structures in which hydrophilic and
      hydrophobic regions are not as clearly separated as chemical surfactants but have
      a more mosaic distribution of polarity as well as branched or circular
      structures. This allows the lipopeptide surfactin to adopt spherical structures
      to facilitate dense packing at interfaces. They are also more complex. Glycolipid
      BS, e.g. rhamnolipids (RL) and sophorolipids, are produced biologically as
      mixtures which vary in the size and saturation of the hydrophobic region as well
      as modifications in the hydrophilic headgroup, such as the number of sugar groups
      and different levels of acetylation, leading to variable surface-active
      properties. Their amphiphilicity allows RL to insert easily into membranes at sub
      cmc concentrations to modulate membrane structure and extract
      lipopolysaccharides, leading to extensive biofilm remodeling in vivo, sometimes
      in collaboration with hydrophobic RL precursors. Thanks to their mosaicity, even
      anionic BS like RL only bind weakly to proteins and show much lower denaturing
      potency, even supporting membrane protein refolding. Nevertheless, they can
      promote protein degradation by proteases e.g. by neutralizing positive charges,
      which together with their biofilm-combating properties makes them very promising
      detergent surfactants. This article is part of a Special Issue entitled: Lipid
      order/lipid defects and lipid-control of protein activity edited by Dirk
      Schneider.

PMID- 27693346
TI  - A survey of herbal weeds for treating skin disorders from Southern Thailand:
      Songkhla and Krabi Province.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Skin diseases are common health problems which
      affecting to all ages. In Thailand, the number of patients diagnosed with skin
      diseases is increasing every year. Nowadays, The Ministry of Public Health is
      supporting and promoting herbs for treating various disorders, including
      disorders of the skin to reduce the problem of antibiotic resistance and adverse
      drug reactions. This study aimed to: (1) enumerate the herbal weeds for treating
      skin disorders; (2) study local knowledge of weed utilization for treating skin
      disorders according to the folk healers in Songkhla and Krabi province; and (3)
      study quantitative data by Informant consensus factor (ICF), Use value (UV) and
      Fidelity level (FL) value. MATERIALS AND METHODS: Field surveys and Semi
      structured interviews about the local names, parts of plants used, preparation
      and use method, as well as local properties were done. The data were further
      analyzed by descriptive statistics, interpretation and quantitative indexes (ICF,
      UV as well as FL). RESULTS: The results discovered 44 herbal species of weeds
      belonging to 41 genera in 25 families. The most used plant families were
      Amaranthaceae (6 species). Most plants were used to treat abscess (18 species;
      40.91%). The highest UV was recorded for Commelina benghalensis (0.65). The
      highest ICF values were found in vitiligo, ringworm, tinea versicolor and burns
      (1.00 each). The highest FL values were recorded for Cleome gynandra, Cleome
      viscosa, Sphenoclea zeylanica, Acmella oleracea, Leersia hexandra, Cyperus
      involucratus, Phyllanthus urinaria and Iresine herbstii (100.00 each). A review
      of the literatures revealed that 34 plant species had already been tested for
      their pharmacological activities. The biological activities associated with
      treatment of skin diseases can be divided into four categories: antimicrobial,
      anti-inflammatory, wound healing and antioxidant activity. CONCLUSION: The
      information indicates that herbal weedy utilization is still importance to the
      treatment of traditional healers through accumulated experience for a long time.
      Therefore, this study is a guide to the conservation of folk medicinal knowledge.
      It might be implied as the basis for drug development and application of herbal
      weeds to treat skin disorders along with promoting sustainable use of natural
      resource.

PMID- 27693348
TI  - How to Effectively Use High-Resolution Esophageal Manometry.

PMID- 27693349
TI  - The Plasmodium alveolin IMC1a is stabilised by its terminal cysteine motifs and
      facilitates sporozoite morphogenesis and infectivity in a dose-dependent manner.
AB  - Apicomplexan parasites possess a unique cortical cytoskeleton structure composed
      of intermediate filaments. Its building blocks are provided by a conserved family
      of proteins named alveolins. The core alveolin structure is made up of tandem
      repeat sequences, thought to be responsible for the filamentous properties of
      these proteins. A subset of alveolins also possess conserved motifs composed of
      three closely spaced cysteine residues situated near the ends of the
      polypeptides. The roles of these cysteine motifs and their contribution to
      alveolin function remains poorly understood. The sporozoite-expressed IMC1a is
      unique within the Plasmodium alveolin family in having conserved cysteine motifs
      at both termini. Using transgenic Plasmodium berghei parasites, we show in this
      structure-function analysis that mutagenesis of the amino- or carboxy-terminal
      cysteine motif causes marked reductions in IMC1a protein levels in the parasite,
      which are accompanied by partial losses of sporozoite shape and infectivity. Our
      findings give new insight into alveolin function, identifying a dose-dependent
      effect of alveolin depletion on sporozoite size and infectivity, and vital roles
      of the terminal cysteine motifs in maintaining alveolin stability in the
      parasite.

PMID- 27693347
TI  - Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in
      African Americans With Inflammatory Bowel Disease.
AB  - BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC)
      and Crohn's disease (CD) cause significant morbidity and are increasing in
      prevalence among all populations, including African Americans. More than 200
      susceptibility loci have been identified in populations of predominantly European
      ancestry, but few loci have been associated with IBD in other ethnicities.
      METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of
      African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel
      disease unclassified) and 5002 individuals without IBD (controls, identified from
      the Health Retirement Study and Kaiser Permanente database). Single-nucleotide
      polymorphisms (SNPs) associated at P < 5.0 * 10-8 in meta-analysis with a nominal
      evidence (P < .05) in each scan were considered to have genome-wide significance.
      RESULTS: We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and
      LSAMP, with associations of genome-wide significance for UC. We detected SNPs at
      USP25 with associations of genome-wide significance for IBD. No associations of
      genome-wide significance were detected for CD. In addition, 9 genes previously
      associated with IBD contained SNPs with significant evidence for replication (P <
      1.6 * 10-6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on
      conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong
      linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC.
      Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated
      with IBD at the HLA locus, contained SNPs with unique association patterns with
      African-specific alleles. CONCLUSIONS: We performed a genome-wide association
      study of African Americans with IBD and identified loci associated with UC in
      only this population; we also replicated IBD, CD, and UC loci identified in
      European populations. The detection of variants associated with IBD risk in only
      people of African descent demonstrates the importance of studying the genetics of
      IBD and other complex diseases in populations beyond those of European ancestry.

PMID- 27693351
TI  - Replication-Dependent Unhooking of DNA Interstrand Cross-Links by the NEIL3
      Glycosylase.
AB  - During eukaryotic DNA interstrand cross-link (ICL) repair, cross-links are
      resolved ("unhooked") by nucleolytic incisions surrounding the lesion. In
      vertebrates, ICL repair is triggered when replication forks collide with the
      lesion, leading to FANCI-FANCD2-dependent unhooking and formation of a double
      strand break (DSB) intermediate. Using Xenopus egg extracts, we describe here a
      replication-coupled ICL repair pathway that does not require incisions or FANCI
      FANCD2. Instead, the ICL is unhooked when one of the two N-glycosyl bonds forming
      the cross-link is cleaved by the DNA glycosylase NEIL3. Cleavage by NEIL3 is the
      primary unhooking mechanism for psoralen and abasic site ICLs. When N-glycosyl
      bond cleavage is prevented, unhooking occurs via FANCI-FANCD2-dependent
      incisions. In summary, we identify an incision-independent unhooking mechanism
      that avoids DSB formation and represents the preferred pathway of ICL repair in a
      vertebrate cell-free system.

PMID- 27693350
TI  - Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T
      Cells.
AB  - The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in
      germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous
      activation of B cell proliferation and drives the development of GC lymphomas in
      vivo. HVEM-deficient lymphoma B cells also induce a tumor-supportive
      microenvironment marked by exacerbated lymphoid stroma activation and increased
      recruitment of T follicular helper (TFH) cells. These changes result from the
      disruption of inhibitory cell-cell interactions between the HVEM and BTLA (B and
      T lymphocyte attenuator) receptors. Accordingly, administration of the HVEM
      ectodomain protein (solHVEM(P37-V202)) binds BTLA and restores tumor suppression.
      To deliver solHVEM to lymphomas in vivo, we engineered CD19-targeted chimeric
      antigen receptor (CAR) T cells that produce solHVEM locally and continuously.
      These modified CAR-T cells show enhanced therapeutic activity against xenografted
      lymphomas. Hence, the HVEM-BTLA axis opposes lymphoma development, and our study
      illustrates the use of CAR-T cells as "micro-pharmacies" able to deliver an anti
      cancer protein.

PMID- 27693352
TI  - Enhancer Variants Synergistically Drive Dysfunction of a Gene Regulatory Network
      In Hirschsprung Disease.
AB  - Common sequence variants in cis-regulatory elements (CREs) are suspected
      etiological causes of complex disorders. We previously identified an intronic
      enhancer variant in the RET gene disrupting SOX10 binding and increasing
      Hirschsprung disease (HSCR) risk 4-fold. We now show that two other functionally
      independent CRE variants, one binding Gata2 and the other binding Rarb, also
      reduce Ret expression and increase risk 2- and 1.7-fold. By studying human and
      mouse fetal gut tissues and cell lines, we demonstrate that reduced RET
      expression propagates throughout its gene regulatory network, exerting effects on
      both its positive and negative feedback components. We also provide evidence that
      the presence of a combination of CRE variants synergistically reduces RET
      expression and its effects throughout the GRN. These studies show how the effects
      of functionally independent non-coding variants in a coordinated gene regulatory
      network amplify their individually small effects, providing a model for complex
      disorders.

PMID- 27693353
TI  - Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic
      Notch Receptors.
AB  - Redirecting T cells to attack cancer using engineered chimeric receptors provides
      powerful new therapeutic capabilities. However, the effectiveness of therapeutic
      T cells is constrained by the endogenous T cell response: certain facets of
      natural response programs can be toxic, whereas other responses, such as the
      ability to overcome tumor immunosuppression, are absent. Thus, the efficacy and
      safety of therapeutic cells could be improved if we could custom sculpt immune
      cell responses. Synthetic Notch (synNotch) receptors induce transcriptional
      activation in response to recognition of user-specified antigens. We show that
      synNotch receptors can be used to sculpt custom response programs in primary T
      cells: they can drive a la carte cytokine secretion profiles, biased T cell
      differentiation, and local delivery of non-native therapeutic payloads, such as
      antibodies, in response to antigen. SynNotch T cells can thus be used as a
      general platform to recognize and remodel local microenvironments associated with
      diverse diseases.

PMID- 27693354
TI  - Functional Metabolomics Describes the Yeast Biosynthetic Regulome.
AB  - Genome-metabolism interactions enable cell growth. To probe the extent of these
      interactions and delineate their functional contributions, we quantified the
      Saccharomyces amino acid metabolome and its response to systematic gene deletion.
      Over one-third of coding genes, in particular those important for chromatin
      dynamics, translation, and transport, contribute to biosynthetic metabolism.
      Specific amino acid signatures characterize genes of similar function. This
      enabled us to exploit functional metabolomics to connect metabolic regulators to
      their effectors, as exemplified by TORC1, whose inhibition in exponentially
      growing cells is shown to match an interruption in endomembrane transport.
      Providing orthogonal information compared to physical and genetic interaction
      networks, metabolomic signatures cluster more than half of the so far
      uncharacterized yeast genes and provide functional annotation for them. A major
      part of coding genes is therefore participating in gene-metabolism interactions
      that expose the metabolism regulatory network and enable access to an
      underexplored space in gene function.

PMID- 27693355
TI  - Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological
      Traits.
AB  - Prions are a paradigm-shifting mechanism of inheritance in which phenotypes are
      encoded by self-templating protein conformations rather than nucleic acids. Here,
      we examine the breadth of protein-based inheritance across the yeast proteome by
      assessing the ability of nearly every open reading frame (ORF; ~5,300 ORFs) to
      induce heritable traits. Transient overexpression of nearly 50 proteins created
      traits that remained heritable long after their expression returned to normal.
      These traits were beneficial, had prion-like patterns of inheritance, were common
      in wild yeasts, and could be transmitted to naive cells with protein alone. Most
      inducing proteins were not known prions and did not form amyloid. Instead, they
      are highly enriched in nucleic acid binding proteins with large intrinsically
      disordered domains that have been widely conserved across evolution. Thus, our
      data establish a common type of protein-based inheritance through which
      intrinsically disordered proteins can drive the emergence of new traits and
      adaptive opportunities.

PMID- 27693356
TI  - IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3
      Inflammasomes.
AB  - The inflammasome is an intracellular signaling complex, which on recognition of
      pathogens and physiological aberration, drives activation of caspase-1,
      pyroptosis, and the release of the pro-inflammatory cytokines IL-1beta and IL-18.
      Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes;
      however, the mechanisms by which concealed ligands are liberated in the cytoplasm
      have remained unclear. Here, we showed that the interferon-inducible protein
      IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by
      Francisella novicida and contributed to the activation of the LPS-sensing caspase
      11 and NLRP3 inflammasome by Gram-negative bacteria. IRGB10 directly targeted
      cytoplasmic bacteria through a mechanism requiring guanylate-binding proteins.
      Localization of IRGB10 to the bacterial cell membrane compromised bacterial
      structural integrity and mediated cytosolic release of ligands for recognition by
      inflammasome sensors. Overall, our results reveal IRGB10 as part of a conserved
      signaling hub at the interface between cell-autonomous immunity and innate immune
      sensing pathways.

PMID- 27693357
TI  - Zika Virus: Immunity and Vaccine Development.
AB  - The emergence of Zika virus in the Americas and Caribbean created an urgent need
      for vaccines to reduce transmission and prevent disease, particularly the
      devastating neurodevelopmental defects that occur in utero. Rapid advances in
      Zika immunity and the development of vaccine candidates provide cautious optimism
      that preventive measures are possible.

PMID- 27693359
TI  - Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA.
AB  - PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs) and
      silence transposable elements in animal gonads. Here, we report the crystal
      structure of a silkworm PIWI-clade Argonaute, Siwi, bound to the endogenous
      piRNA, at 2.4 A resolution. Siwi adopts a bilobed architecture consisting of N
      PAZ and MID-PIWI lobes, in which the 5' and 3' ends of the bound piRNA are
      anchored by the MID-PIWI and PAZ domains, respectively. A structural comparison
      of Siwi with AGO-clade Argonautes reveals notable differences in their nucleic
      acid-binding channels, likely reflecting the distinct lengths of their guide RNAs
      and their mechanistic differences in guide RNA loading and cleavage product
      release. In addition, the structure reveals that Siwi and prokaryotic, but not
      eukaryotic, AGO-clade Argonautes share unexpected similarities, such as metal
      dependent 5'-phosphate recognition and a potential structural transition during
      the catalytic-tetrad formation. Overall, this study provides a critical starting
      point toward a mechanistic understanding of piRNA-mediated transposon silencing.

PMID- 27693360
TI  - Eimeria spp. infecting quenda (Isoodon obesulus) in the greater Perth region,
      Western Australia.
AB  - Parasites of wildlife inhabiting urbanised and peri-urban environments are of
      interest regarding wildlife population health, and also veterinary public health
      in the case of parasites that can also infect humans and domestic animals. This
      study aimed to: identify, and estimate the prevalence of, species of Eimeria
      parasitic in quenda (Isoodon obesulus) in the greater Perth region, Western
      Australia; 2) morphologically describe and genetically characterise a novel
      observed species of Eimeria as E. angustus; and 3) genetically characterise E.
      kanyana. Eimeria spp. prevalence was 76.1% (95% CI 64.9-84.5%), and four putative
      species of Eimeria were identified. Eimeria kanyana was identified infecting
      quenda for the first time, with a prevalence of 54.9% (43.4-66.0%). Eimeria
      quenda was less prevalent, at 7.0% (3.1-15.5%). The novel species E. angustus was
      present in 45.1% of sampled quenda (34.0-56.6%). A second novel morphotype of
      Eimeria was present in 2.8% of sampled quenda (0.9-9.7%). Mixed Eimeria spp.
      infections were present in 21/71 quenda (29.6%, 95% CI 20.2-41.1%). Molecular
      phylogenetic analyses of E. kanyana and E. angustus were conducted at the 18S
      rRNA and mitochondrial cytochrome oxidase loci. At both loci, two isolates
      identified as E. kanyana grouped in a phylogenetic clade with E. trichosuri. Five
      isolates identified as the novel E. angustus were most closely related to E.
      tropidura at the 18S locus. At the COI locus, no sequence data were available for
      E. tropidura; isolates of E. angustus grouped with E. sciurorum.

PMID- 27693358
TI  - Mitochondrial Protein Synthesis Adapts to Influx of Nuclear-Encoded Protein.
AB  - Mitochondrial ribosomes translate membrane integral core subunits of the
      oxidative phosphorylation system encoded by mtDNA. These translation products
      associate with nuclear-encoded, imported proteins to form enzyme complexes that
      produce ATP. Here, we show that human mitochondrial ribosomes display
      translational plasticity to cope with the supply of imported nuclear-encoded
      subunits. Ribosomes expressing mitochondrial-encoded COX1 mRNA selectively engage
      with cytochrome c oxidase assembly factors in the inner membrane. Assembly
      defects of the cytochrome c oxidase arrest mitochondrial translation in a
      ribosome nascent chain complex with a partially membrane-inserted COX1
      translation product. This complex represents a primed state of the translation
      product that can be retrieved for assembly. These findings establish a mammalian
      translational plasticity pathway in mitochondria that enables adaptation of
      mitochondrial protein synthesis to the influx of nuclear-encoded subunits.

PMID- 27693361
TI  - A nanotechnology based new approach for Trypanosoma evansi chemotherapy: In vitro
      and vivo trypanocidal effect of (-)-alpha-bisabolol.
AB  - The aim of this study was to evaluate the in vitro and in vivo susceptibility of
      Trypanosoma evansi to alpha-Bisabolol and solid lipid nanoparticles containing
      alpha-Bisabolol (SLN-B). In vitro, a trypanocidal effect of alpha-Bisabolol and
      SLN-B was observed when used at 0.5, 1 and 2% concentrations, i.e., the
      concentrations of 1 and 2% showed a faster trypanocidal effect when compared to
      chemotherapy (diminazene aceturate - D.A.). T. evansi infected mice were treated
      with alpha-Bisabolol and SLN-B at a dose of 1.0 mL kg-1 during seven days via
      oral gavage. In vivo, treatment with SLN-B, D.A. and D.A. associated with SLN-B
      were able to increase (p < 0.05) the pre-patent period and longevity when
      compared to positive control (infected and untreated animals), but showed no
      curative efficacy. T. evansi infected mice treated with D.A. associate with SLN
      B, where a curative efficacy of 50% was found, a much better result when D. A and
      SLN-B were used alone (16.66%). In summary, the association with D. A + SLN-B can
      be used as an alternative to improve the therapeutic effectiveness of D.A., and
      for treatment of infected animals with T. evansi. Also, the nanotechnology
      associated with natural products arises an important alternative for the improve
      the trypanocidal action.

PMID- 27693362
TI  - Over-the-scope clip for endoscopic closure of gastrogastric fistulae.
AB  - BACKGROUND: Gastrogastric fistulae (GGF) are a well-known complication of Roux-en
      Y gastric bypass (RYGB). Endoscopic approaches for closure of GGF have gained
      popularity, but with limited data and efficacy. OBJECTIVES: The primary arm of
      the study was to evaluate the safety and efficacy of the endoscopic closure of
      GGF using the over-the-scope clip (OTSC) device. SETTING: University hospital,
      United States METHODS: This is a retrospective review of consecutive patients at
      a single academic center from September 2013 to December 2014 who underwent upper
      endoscopy with attempted OTSC placement for closure of GGF related to RYGB.
      Preprocedural, procedural, and postprocedural data were collected. Outcome
      measures included technical success, primary success, and long-term success.
      RESULTS: A total of 14 patients underwent attempted GGF closure using OTSC.
      Twelve of the 14 patients (85.7%) had technical success. Four patients were lost
      to follow-up. Primary success was achieved in 5 of the 10 patients (50%) in which
      it was assessed, either by upper gastrointestinal series or endoscopy. One of the
      5 patients who had primary success was then lost to follow-up. Of the 4 patients
      in whom primary success was achieved and had long-term follow up, 75% (n = 3)
      achieved long-term success at a mean follow-up of 6.6 months from initial OTSC
      placement (range, 3-9), making for a long-term success rate of 33% (3/9). There
      were no reported complications. CONCLUSION: OTSC closure of small GGF is
      feasible, safe, and offers a reasonable alternative to surgical revision. Large
      GGF may undergo attempted endoscopic closure, acknowledging a high failure rate.

PMID- 27693363
TI  - 3D pharmacophore-based virtual screening, docking and density functional theory
      approach towards the discovery of novel human epidermal growth factor receptor-2
      (HER2) inhibitors.
AB  - Human epidermal growth factor receptor 2 (HER2) is one of the four members of the
      epidermal growth factor receptor (EGFR) family and is expressed to facilitate
      cellular proliferation across various tissue types. Therapies targeting HER2,
      which is a transmembrane glycoprotein with tyrosine kinase activity, offer
      promising prospects especially in breast and gastric/gastroesophageal cancer
      patients. Persistence of both primary and acquired resistance to various routine
      drugs/antibodies is a disappointing outcome in the treatment of many HER2
      positive cancer patients and is a challenge that requires formulation of new and
      improved strategies to overcome the same. Identification of novel HER2 inhibitors
      with improved therapeutics index was performed with a highly correlating
      (r=0.975) ligand-based pharmacophore model (Hypo1) in this study. Hypo1 was
      generated from a training set of 22 compounds with HER2 inhibitory activity and
      this well-validated hypothesis was subsequently used as a 3D query to screen
      compounds in a total of four databases of which two were natural product
      databases. Further, these compounds were analyzed for compliance with Veber's
      drug-likeness rule and optimum ADMET parameters. The selected compounds were then
      subjected to molecular docking and Density Functional Theory (DFT) analysis to
      discern their molecular interactions at the active site of HER2. The findings
      thus presented would be an important starting point towards the development of
      novel HER2 inhibitors using well-validated computational techniques.

PMID- 27693364
TI  - Viral infections of oceanic plankton blooms.
AB  - Viruses are known to impact blooms of phytoplankton in the ocean, in some cases
      causing the bloom to crash. Here, using a population model that includes viral
      infection, we investigate the conditions under which the presence of a virus
      significantly impacts the population dynamics. A major focus is how spatial
      variability influences the spread of an epidemic in a stirring and mixing field.
      The combination of viral infection and diffusion can cause waves of the epidemic
      to sweep through the domain, with the epidemic lasting much longer than in the
      homogeneous case. Stirring by the fluid flow can greatly increase this effect
      causing an increase in the fraction of the bloom that is affected and in certain
      circumstances (high diffusion and stirring) can totally suppress the bloom. The
      fluid environment affects the relative spatial structure of the components of the
      system. High values of the concentrations of the virus and infected phytoplankton
      are found in thin filaments along fronts of uninfected (susceptible)
      phytoplankton.

PMID- 27693365
TI  - Hydra effects in discrete-time models of stable communities.
AB  - A species exhibits a hydra effect when, counter-intuitively, increased mortality
      of the species causes an increase in its abundance. Hydra effects have been
      studied in many continuous time (differential equation) multispecies models, but
      only rarely have hydra effects been observed in or studied with discrete time
      (difference equation) multispecies models. In addition most discrete time theory
      focuses on single-species models. Thus, it is unclear what unifying
      characteristics determine when hydra effects arise in discrete time models. Here,
      using discrete time multispecies models (where total abundance is the single
      variable describing each population), I show that a species exhibits a hydra
      effect in a stable system only when fixing that species' density at its
      equilibrium density destabilizes the system. This general characteristic is
      referred to as subsystem instability. I apply this result to two-species models
      and identify specific mechanisms that cause hydra effects in stable communities,
      e.g., in host--parasitoid models, host Allee effects and saturating parasitoid
      functional responses can cause parasitoid hydra effects. I discuss how the
      general characteristic can be used to identify mechanisms causing hydra effects
      in communities with three or more species. I also show that the condition for
      hydra effects at stable equilibria implies the system is reactive (i.e., density
      perturbations can grow before ultimately declining). This study extends previous
      work on conditions for hydra effects in single-species models by identifying
      necessary conditions for stable systems and sufficient conditions for cyclic
      systems. In total, these results show that hydra effects can arise in many more
      communities than previously appreciated and that hydra effects were present, but
      unrecognized, in previously studied discrete time models.

PMID- 27693366
TI  - Exploring optimal control strategies in seasonally varying flu-like epidemics.
AB  - The impact of optimal control strategies in the context of seasonally varying
      infectious disease transmission remains a wide open research area. We investigate
      optimal control strategies for flu-like epidemics using an SIR (susceptible
      infectious-recovered) type epidemic model where the transmission rate varies
      seasonally Specifically, we explore optimal control strategies using time
      dependent treatment and vaccination as control functions alone or in combination.
      Optimal strategies and associated epidemic outcomes are contrasted for epidemics
      with constant and seasonal transmission rates. Our results show that the epidemic
      outcomes assessed in terms of the timing and size of seasonal epidemics subject
      to optimal control strategies are highly sensitive to various parameters
      including R0, the timing of the introduction of the initial number of infectious
      individuals into the population, the time at which interventions start, and the
      strength of the seasonal forcing that modulates the time-dependent transmission
      rate. Findings highlight the difficult challenge in predicting short-term
      epidemic impact in the context of seasonally varying infectious disease
      transmission with some interventions scenarios exhibiting larger epidemic size
      compared to scenarios without control interventions.

PMID- 27693367
TI  - The immune system of the gut and potential adverse effects of oral nanocarriers
      on its function.
AB  - There is substantial effort in modern pharmacotherapy to use nanoparticle-based
      drug delivery systems (nDDS) for improving the oral absorption of drugs. An often
      neglected circumstance regarding this approach is that the gut is a major part of
      the immune system that may be vulnerable for immune-cell toxicity, or mediate
      humoral immune response against various components of nDDS, recognized as
      foreign. This review recapitulates the structure and function of gut-associated
      lymphoid tissue (GALT), i.e., the enteral section of mucosa-associated lymphoid
      tissue (MALT) and reminds how virus-like nDDS may potentially induce
      immunogenicity just as attenuated or killed viruses do in oral vaccines.
      Furthermore, we present examples for immune toxicities of emulsifiers and polymer
      containing micelles, manifested in complement activation-related pseudoallergy
      (CARPA). A major message of the review is that early testing of immunogenicity or
      other adverse immune effects of nDDS in appropriate test systems or models may be
      prudent to recognize the risk of rare immune problems that may surface in late
      stage clinical trials or after marketing of nDDS.

PMID- 27693368
TI  - The Relationship Between Resistant Tachycardia and Treatment for GERD.
AB  - : The use of medications that block gastric acid secretion, such as proton pump
      inhibitors, has rapidly escalated in the United States. Although originally
      intended for short-term treatment of specific conditions, PPIs have expanded to
      long-term use with unanticipated consequences, including mineral deficiencies
      related to lack of sufficient stomach acid needed for extraction of minerals from
      the foods and supplements ingested. Herein, the author reports on a case of a
      patient with tachycardia and other arrhythmias that had been resistant to the
      medications prescribed by a series of cardiologists. The patient had been on PPI
      for several years preceding his arrhythmias, prescribed for stress-related
      gastritis. The author did comprehensive blood work and discovered that the
      patient was deficient in many of the minerals tested, including magnesium, known
      to be essential for normal cardiac function. After the patient slowly weaned
      himself off the PPIs and took magnesium and other minerals, the tachycardia
      resolved without any medication. CONCLUSIONS: This case demonstrates the
      importance of carefully reviewing the list of medications patients are taking and
      having a thorough understanding of the possible long-term risks associated with
      those medications. The patient's presenting symptoms have the potential to be
      related-directly or indirectly-to the medications that have been prescribed.

PMID- 27693370
TI  - CASZ1 loss-of-function mutation associated with congenital heart disease.
AB  - As the most common form of birth defect in humans, congenital heart disease (CHD)
      is associated with substantial morbidity and mortality in both children and
      adults. Increasing evidence demonstrates that genetic defects play a pivotal role
      in the pathogenesis of CHD. However, CHD is of great heterogeneity, and in an
      overwhelming majority of cases, the genetic determinants underpinning CHD remain
      elusive. In the present investigation, the coding exons and flanking introns of
      the CASZ1 gene, which codes for a zinc finger transcription factor essential for
      the cardiovascular morphogenesis, were sequenced in 172 unrelated patients with
      CHD. As a result, a novel heterozygous CASZ1 mutation, p.L38P, was identified in
      an index patient with congenital ventricular septal defect (VSD). Genetic
      scanning of the mutation carrier's available family members revealed that the
      mutation was present in all affected patients but absent in unaffected
      individuals. Analysis of the proband's pedigree showed that the mutation co
      segregated with VSD, which was transmitted as an autosomal dominant trait with
      complete penetrance. The missense mutation, which altered the amino acid that was
      highly conserved evolutionarily, was absent in 200 unrelated, ethnically-matched
      healthy subjects used as controls. Functional deciphers by using a dual
      luciferase reporter assay system unveiled that the mutant CASZ1 had significantly
      reduced transcriptional activity as compared with its wild-type counterpart. To
      the best of our knowledge, the current study firstly identifies CASZ1 as a new
      gene predisposing to CHD in humans, which provides novel insight into the
      molecular mechanisms underlying CHD and a potential therapeutic target for CASZ1
      associated CHD, suggesting potential implications for personalized prophylaxis
      and therapy of CHD.

PMID- 27693371
TI  - JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori)
      challenged by Beauveria bassiana.
AB  - Innate immunity was critical in insects defensive system and able to be induced
      by Janus kinase/signal transducer and activator of transcription cascade
      transduction (JAK/STAT) signaling pathway. Currently, it had been identified many
      JAK/STAT signaling pathway-related genes in silkworm, but little function was
      known on insect innate immunity. To explore the roles of JAK/STAT pathway in
      antifungal immune response in silkworm (Bombyx mori) against Beauveria bassiana
      infection, the expression patterns of B. mori C-type lectin 5 (BmCTL5) and genes
      encoding 6 components of JAK/STAT signaling pathway in silkworm challenged by B.
      bassiana were analyzed using quantitative real time PCR. Meanwhile the activation
      of JAK/STAT signaling pathway by various pathogenic micro-organisms and the
      affect of JAK/STAT signaling pathway inhibitors on antifungal activity in
      silkworm hemolymph was also detected. Moreover, RNAi assay of BmCTL5 and the
      affect on expression levels of signaling factors were also analyzed. We found
      that JAK/STAT pathway could be obviously activated in silkworm challenged with B.
      bassiana and had no response to bacteria and B. mori cytoplasmic polyhedrosis
      virus (BmCPV). However, the temporal expression patterns of JAK/STAT signaling
      pathway related genes were significantly different. B. mori downstream receptor
      kinase (BmDRK) might be a positive regulator of JAK/STAT signaling pathway in
      silkworm against B. bassiana infection. Moreover, antifungal activity assay
      showed that the suppression of JAK/STAT signaling pathway by inhibitors could
      significantly inhibit the antifungal activity in hemolymph and resulted in
      increased sensitivity of silkworm to B. bassiana infection, indicating that
      JAK/STAT signaling pathway might be involved in the synthesis and secretion of
      antifungal substances. The results of RNAi assays suggested that BmCTL5 might be
      one pattern recognition receptors for JAK/STAT signaling pathway in silkworm.
      These findings yield insights for better understand the molecular mechanisms of
      JAK/STAT signaling pathway in antifungal immune response in silkworm.

PMID- 27693369
TI  - Embryonic origin and lineage hierarchies of the neural progenitor subtypes
      building the zebrafish adult midbrain.
AB  - Neurogenesis in the post-embryonic vertebrate brain varies in extent and
      efficiency between species and brain territories. Distinct neurogenesis modes may
      account for this diversity, and several neural progenitor subtypes, radial glial
      cells (RG) and neuroepithelial progenitors (NE), have been identified in the
      adult zebrafish brain. The neurogenic sequences issued from these progenitors,
      and their contribution to brain construction, remain incompletely understood.
      Here we use genetic tracing techniques based on conditional Cre recombination and
      Tet-On neuronal birthdating to unravel the neurogenic sequence operating from NE
      progenitors in the zebrafish post-embryonic optic tectum. We reveal that a
      subpopulation of her5-positive NE cells of the posterior midbrain layer stands at
      the top of a neurogenic hierarchy involving, in order, the amplification pool of
      the tectal proliferation zone (TPZ), followed by her4-positive RG cells with
      transient neurogenic activity. We further demonstrate that the adult her5
      positive NE pool is issued in lineage from an identically located NE pool
      expressing the same gene in the embryonic neural tube. Finally, we show that
      these features are reminiscent of the neurogenic sequence and embryonic origin of
      the her9-positive progenitor NE pool involved in the construction of the lateral
      pallium at post-embryonic stages. Together, our results highlight the shared
      recruitment of an identical neurogenic strategy by two remote brain territories,
      where long-lasting NE pools serve both as a growth zone and as the life-long
      source of young neurogenic RG cells.

PMID- 27693372
TI  - Characterization and comparative profiling of the small RNA transcriptomes in the
      Hemipteran insect Nilaparvata lugens.
AB  - MicroRNAs (miRNAs) are a group of small RNAs involved in various biological
      processes through negative regulation of mRNAs at the post-transcriptional level.
      The brown planthopper (BPH), Nilaparvata lugens (Stal), is one of the most
      serious and destructive insect pests of rice. In the present study, two small RNA
      libraries of virulent N. lugens populations (Biotype I survives on susceptive
      rice variety TN1 and Biotype Y survives on moderately resistant rice variety
      YHY15) were constructed and sequenced using the high-throughput sequencing
      technology in order to identify the relationship between miRNAs of N.lugens and
      adaptation of BPH pests to rice resistance. In total 15,758,632 and 11,442,592
      reads, corresponding to 3,144,026 and 2,550,049 unique sequences, were obtained
      in the two libraries (BPH-TN1 and BPH-YHY15 libraries), respectively. A total of
      41 potential novel miRNAs were predicted in the two libraries, and 26 miRNAs
      showed significantly differential expression between two libraries. All miRNAs
      were significantly up-regulated in the BPH-TN1 library. Target genes likely
      regulated by these differentially expressed miRNAs were predicted using
      computational prediction. The functional annotation of target genes performed by
      Gene Ontology enrichment (GO) and Kyoto Encyclopedia of Genes and Genomes pathway
      analysis (KEGG) indicated that a majority of differential miRNAs were involved in
      "Metabolism" pathway. These results provided an understanding of the role of
      miRNAs in BPH to adaptability of BPH on rice resistance, and will be useful in
      developing new control strategies for host defense against BPH.

PMID- 27693374
TI  - Acne and Telomere Length: A New Spectrum between Senescence and Apoptosis
      Pathways.

PMID- 27693375
TI  - Patient perceptions of clinical care in complementary medicine: A systematic
      review of the consultation experience.
AB  - OBJECTIVE: This review aims to describe the prevalence of empathy, empowerment
      and patient-centred clinical care experienced by patients in complementary
      medicine (CM) consultations. METHODS: A systematic review was undertaken of
      original research exploring patient perceptions of CM clinical care. Ten
      databases were searched: Alt HealthWatch, AMED, CINAHL Plus, MEDLINE Complete,
      Cochrane Library, PubMed, Proquest Medical Collection, PsycInfo, Social Sciences
      Citation Index and Psychology Collection. Studies were included which reported
      patient perceptions of consultation with CM practitioners and were excluded where
      experimental methods controlled the nature of consultation processes. RESULTS:
      Findings of included studies (n=34) were categorised under the a priori themes of
      empathy, empowerment and patient-centred care. This produced a substantial pool
      of qualitative data detailing patient-reported experiences which consistently
      confirmed occurrence of these themes in CM consultation. Quantitative data was
      correlative, yet was insufficient to definitively describe prevalence of such
      experiences. CONCLUSION: While it is evident that CM consultations provide a
      patient experience of empathy, empowerment and patient-centredness, further
      research is warranted to quantify this experience before it can be defined as
      characteristic of CM clinical care. PRACTICE IMPLICATIONS: This review draws
      attention to the potential role of CM as a resource for patients' psychosocial
      health needs.

PMID- 27693373
TI  - Ruthenium-Clotrimazole complex has significant efficacy in the murine model of
      cutaneous leishmaniasis.
AB  - In previous studies we reported a novel series of organometallic compounds, RuII
      complexed with clotrimazole, displaying potent trypanosomatid activity with
      unnoticeable toxicity toward normal mammalian cells. In view of the promising
      activity of Ru-clotrimazole complexes against Leishmania major (L. major), the
      present work sought to investigate the anti-leishmanial activity of the AM162
      complex in the murine model of cutaneous leishmaniasis. In addition, to
      facilitate the design of new therapeutic strategies against this disease, we
      investigated the mode of action of two Ru-clotrimazole complexes in L. major
      promastigotes. Overall, we demonstrate that AM162 significantly reduced the
      lesion size in mice exposed to L. major infection. In addition, Ru-clotrimazole
      compounds are able to induce a mitochondrial dependent apoptotic-like death in
      the extracellular form of the parasite based on labeling of DNA fragments,
      mitochondrial depolarization, cell cycle alteration profile and plasma membrane
      phospholipid externalization. Our findings reveal a promising efficacy of the Ru
      clotrimazole AM162 complex for the treatment of cutaneous leishmaniasis, as well
      as pro-apoptotic activity and thus guarantees further evaluation in pre-clinical
      studies.

PMID- 27693376
TI  - Morphogenesis and proliferative rule of porcine transmissible gastroenteritis
      virus in porcine intestinal epithelial cells.
AB  - To gain a better understanding of the replication, proliferation and infection
      characteristics of porcine transmissible gastroenteritis virus (TGEV) in porcine
      intestinal epithelial cells (IECs), this study established a cell model of IECs
      infected with the Chongqing (CQ) strain of TGEV. The morphogenesis and
      proliferative rule of TGEV in porcine IECs were investigated using transmission
      electron microscopy, indirect immunofluorescence assays and real-time
      fluorescence quantitative PCR. Observations under the TEM indicated that the
      enveloped viral particles were roughly spherical, with diameters of between 80
      and 120nm. The virions entered porcine IECs by membrane fusion and the mature
      viruses in the vacuoles were transported to the cell membrane before release. The
      results also showed that from 0 to 12h after TGEV infection of porcine IECs, the
      intracellular viral RNA content did not change significantly. Logarithmic growth
      occurred from 12 to 36h, after which it gradually decreased. Moreover, the
      extracellular RNA content began to rise at 24h after inoculation and then reduced
      gradually at approximately 48h. This study provided a theoretical foundation for
      further study on the infection characteristics of TGEV in target cells.

PMID- 27693379
TI  - Ferriheme catalyzes nitric oxide reaction with glutathione to form S
      nitrosoglutathione: A novel mechanism for formation of S-nitrosothiols.
AB  - S-nitrosothiols (SNO) perform many important functions in biological systems, but
      the mechanism by which they are generated in vivo remains a contentious issue.
      Nitric oxide (NO) reacts with thiols to form SNO only in the presence of a
      molecule that will accept an electron from either NO or the thiol. In this study,
      we present evidence that ferriheme accepts an electron from NO or glutathione
      (GSH) to generate S-nitrosoglutathione (GSNO) in vitro under anaerobic or hypoxic
      (2% O2) conditions. Ferriheme formed charge transfer-stable complexes with NO to
      form ferriheme-NO (heme-Fe(II)-NO+) and with GSH to form ferriheme-GS (heme
      Fe(II)-GS*) under anaerobic conditions. The reaction between GSH and the heme
      Fe(II)-NO+ complex or between NO and the heme-Fe(II)-GS* complex resulted in
      simultaneous reductive ferriheme nitrosylation (heme-Fe(II)NO) and the generation
      of GSNO. Thus, ferriheme is readily reduced to ferroheme in the presence of NO
      and GSH together, but not with either individually. The reaction between NO and
      the heme-Fe(II)-GS* complex to generate GSNO occurred more rapidly than NO was
      consumed by endothelial cells, but not red blood cells. In addition, pretreatment
      of endothelial cells with ferriheme or the ferriheme-GS complex generated SNO
      upon addition of NO under hypoxic conditions. The results of this study raise the
      possibility that in vivo, ferriheme can complex with GSH to form ferriheme-GS
      complex (heme-Fe(II)-GS*), which rapidly reacts with NO to generate GSNO under
      intracellular oxygen levels. The GSNO formation by this mechanism is more
      efficient than any other in vitro mechanism(s) reported so far.

PMID- 27693377
TI  - Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric
      Framework.
AB  - Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated
      by protein restriction. Although FGF21 is robustly elevated in low-protein
      environments, increased FGF21 is also seen in various other contexts such as
      fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its
      nutritional context and physiological role unresolved and controversial. Here, we
      use the Geometric Framework, a nutritional modeling platform, to help reconcile
      these apparently conflicting findings in mice confined to one of 25 diets that
      varied in protein, carbohydrate, and fat content. We show that FGF21 was elevated
      under low protein intakes and maximally when low protein was coupled with high
      carbohydrate intakes. Our results explain how elevation of FGF21 occurs both
      under starvation and hyperphagia, and show that the metabolic outcomes associated
      with elevated FGF21 depend on the nutritional context, differing according to
      whether the animal is in a state of under- or overfeeding.

PMID- 27693380
TI  - Perturbation of redox balance after thioredoxin reductase deficiency interrupts
      autophagy-lysosomal degradation pathway and enhances cell death in nutritionally
      stressed SH-SY5Y cells.
AB  - Oxidative damage and aggregation of cellular proteins is a hallmark of neuronal
      cell death after neurotrauma and chronic neurodegenerative conditions. Autophagy
      and ubiquitin protease system are involved in degradation of protein aggregates,
      and interruption of their function is linked to apoptotic cell death in these
      diseases. Oxidative modification of cysteine groups in key molecular proteins has
      been linked to modification of cellular systems and cell death in these
      conditions. Glutathione and thioredoxin systems provide reducing protons that can
      effectively reverse protein modifications and promote cell survival. The central
      role of Thioredoxin in inhibition of apoptosis is well identified. Additionally,
      its involvement in initiation of autophagy has been suggested recently. We
      therefore aimed to investigate the involvement of Thioredoxin system in autophagy
      apoptosis processes. A model of serum deprivation in SH-SY5Y was used that is
      associated with autophagy and apoptosis. Using pharmacological and RNA-editing
      technology we show that Thioredoxin reductase deficiency in this model enhances
      oxidative stress and interrupts the early protective autophagy and promotes
      apoptosis. This was associated with decreased protein-degradation in lysosomes
      due to altered lysosomal acidification and accumulation of autophagosomes as well
      as impairment in proteasome pathway. We further confirmed that the extent of
      oxidative stress is a determining factor in autophagy- apoptosis interplay, as
      upregulation of cellular reducing capacity by N-acetylcysteine prevented
      impairment in autophagy and proteasome systems thus promoted cell viability. Our
      study provides evidence that excessive oxidative stress inhibits protein
      degradation systems and affects the final stages of autophagy by inhibiting
      autolysosome maturation: a novel mechanistic link between protein aggregation and
      conversion of autophagy to apoptosis that can be applicable to neurodegenerative
      diseases.

PMID- 27693378
TI  - Tissue Immunometabolism: Development, Physiology, and Pathobiology.
AB  - Evolution of metazoans resulted in the specialization of cellular and tissue
      function. This was accomplished by division of labor, which allowed tissue
      parenchymal cells to prioritize their core functions while ancillary functions
      were delegated to tissue accessory cells, such as immune, stromal, and
      endothelial cells. In metabolic organs, the accessory cells communicate with
      their clients, the tissue parenchymal cells, to optimize cellular processes,
      allowing organisms to adapt to changes in their environment. Here, we discuss
      tissue immunometabolism from this vantage point and use examples from adipose
      tissues (white, beige, and brown) and liver to outline the general principles by
      which accessory cells support metabolic homeostasis in parenchymal cells. A
      corollary of this model is that disruption of communication between client and
      accessory cells might predispose metabolic organs to the development of disease.

PMID- 27693382
TI  - Effects of physical exercise on myokines expression and brown adipose-like
      phenotype modulation in rats fed a high-fat diet.
AB  - AIMS: Exercise-stimulated myokine secretion into circulation may be related with
      browning in white adipose tissue (WAT), representing a positive metabolic effect
      on whole-body fat mass. However, limited information is yet available regarding
      the impact of exercise on myokine-related modulation of adipocyte phenotype in
      WAT from obese rats. MAIN METHODS: Sprague-Dawley rats (n=60) were divided into
      sedentary and voluntary physical activity (VPA) groups and fed with standard
      (35kcal% fat) or high-fat (HFD, 71kcal% fat)-isoenergetic diets. The VPA-groups
      had unrestricted access to wheel running throughout the protocol. After-9weeks,
      half of sedentary standard (SS) and sedentary HFD (HS)-fed animals were exercised
      on treadmill (endurance training, ET) for 8-weeks while maintaining the dietary
      treatments. KEY FINDINGS: The adipocyte hypertrophy induced by HFD were
      attenuated by VPA and ET. HFD decreased 5' AMP-activated protein kinase (AMPK)
      activity in muscle as well as peroxisome proliferator-activated receptor gamma
      coactivator-1alpha (PGC-1alpha) and uncoupling protein 1 (UCP1) proteins in eWAT,
      while not affecting circulating irisin. VPA increased eWAT Tmem26 mRNA levels in
      the standard diet-fed group, whereas ET increased AMPK, interleukin 6 (IL-6) and
      fibronectin type III domain-containing protein 5 (FNDC5) protein expression in
      muscle, but had no impact on circulating irisin protein content. In eWAT, ET
      increased bone morphogenetic protein 7 (Bmp7), Cidea and PGC-1alpha in both diet
      fed animals, whereas BMP7, Prdm16, UCP1 and FNDC5 only in standard diet-fed
      group. SIGNIFICANCE: Data suggest that ET-induced myokine production seems to
      contribute, at least in part, to the "brown-like" phenotype in WAT from rats fed
      a HFD.

PMID- 27693381
TI  - Disrupted mitochondrial genes and inflammation following stroke.
AB  - AIMS: Determine the subacute time course of mitochondria disruption, cell death,
      and inflammation in a rat model of unilateral motor cortical ischemic stroke.
      MAIN METHODS: Rats received unilateral ischemia of the motor cortex and were
      tested on behavioral tasks to determine impairments. Animals were euthanized at
      24h, 72h and 144h and mRNA expression of key mitochondria proteins and indicators
      of inflammation, apoptosis and potential regenerative processes in ipsilesion
      cortex and striatum, using RT-qPCR. Mitochondrial proteins were examined at 144h
      using immunoblot analysis. KEY FINDINGS: Rats with stroke induced-behavioral
      deficits had sustained, 144h post-lesion, decreases in mitochondrial-encoded
      electron transport chain proteins NADH dehydrogenase subunit-1 and cytochrome c
      oxidase subunit-1 (mRNA and protein) and mitochondrial DNA content in perilesion
      motor and sensory cortex. Uncoupling-protein-2 gene expression, but not
      superoxide dismutase-2, remained elevated in ipsilateral cortex and striatum at
      this time. Cortical inflammatory cytokine, interleukin-6, was increased early and
      was followed by increased macrophage marker F4/80 after stroke. Cleaved caspase-3
      activation was elevated in cortex and growth associated protein-43 was elevated
      in the cortex and striatum six days post-lesion. SIGNIFICANCE: We identified a
      relationship between three disrupted pathways, (1) sustained loss of
      mitochondrial proteins and mitochondrial DNA copy number in the cortex linked to
      decreased mitochondrial gene transcription; (2) early inflammatory response
      mediated by interleukin- 6 followed by macrophages; (3) apoptosis in conjunction
      with the activation of regenerative pathways. The stroke-induced spatial and
      temporal profiles lay the foundation to target pharmacological therapeutics to
      these three pathways.

PMID- 27693383
TI  - Intranasal insulin improves cerebral blood flow, Nrf-2 expression and BDNF in STZ
      (ICV)-induced memory impaired rats.
AB  - AIMS: Insulin/insulin receptor signaling is involved in cognitive functions.
      Clinical studies have shown that intranasal insulin administration improves
      memory functions. However, the molecular mechanisms associated with improvement
      in memory functions are largely unexplored. Therefore, we investigated the
      protective effect of intranasal insulin in intracerebroventricular (ICV)
      streptozotocin (STZ) induced memory impairment in rats. MAIN METHODS: Rats were
      injected with STZ (3mg/kg, ICV) bilaterally twice, on days 1 and 3 and intranasal
      insulin (2IU/rat/day) was given for 14days. Memory was assessed by Morris water
      maze test. Cerebral blood flow (CBF) was measured by laser-Doppler flowmetry. The
      biochemical and molecular studies were done in cortex and hippocampus of rat
      brain. KEY FINDINGS: STZ (ICV) administration caused memory impairment along with
      the reduction of CBF, ATP level, and Nrf-2 expression. Treatment with intranasal
      insulin significantly improved memory functions as well as restored CBF, ATP
      content and Nrf-2 expression in STZ injected rats. STZ administration stimulated
      oxidative-nitrosative stress as evidenced by a significant increase in ROS,
      malondialdehyde, NO level and inducible nitric oxide synthase expression and the
      decrease in glutathione level; which was normalized by intranasal insulin
      delivery. STZ-induced cholinergic dysfunction (AChE activity and alpha7-nAChR
      expression), and mitochondrial hypofunction was largely prevented by treatment
      with intranasal insulin. Intranasal insulin delivery successfully restored BDNF
      level and pCREB expression in STZ injected rats. SIGNIFICANCE: The study shows
      the beneficial effects of intranasal insulin against STZ-induced memory
      impairment, which attributed to improved CBF, cholinergic function, brain energy
      metabolism, BDNF, Nrf-2 expression and antioxidative action.

PMID- 27693384
TI  - A novel inhibitor of BCL2, Disarib abrogates tumor growth while sparing
      platelets, by activating intrinsic pathway of apoptosis.
AB  - Antiapoptotic protein BCL2, serves as an excellent target for anticancer therapy
      owing to its increased level in cancers. Previously, we have described
      characterization of a novel BCL2 inhibitor, Disarib, which showed selective
      cytotoxicity in BCL2 'high' cancer cells and CLL patient cells. Here, we have
      investigated the mechanism of Disarib-induced cytotoxicity, and compared its
      efficacy with a well-established BCL2 inhibitor, ABT199. We show that Disarib
      administration caused tumor regression in mouse allograft and xenograft models,
      exhibited platelet sparing property and did not exhibit significant side effects.
      Importantly, comparison between Disarib and ABT199, revealed higher efficacy for
      Disarib in mouse tumor model and cancer cell lines. Disarib induced cell death by
      activating intrinsic apoptotic pathway. Interestingly, Disarib showed synergism
      with paclitaxel, suggesting its potential for combination therapy. Thus, we
      provide mechanistic insights into the cell death pathways induced by Disarib,
      report that Disarib exhibited better effect than currently used ABT199 and
      demonstrate its combinatorial potential with paclitaxel.

PMID- 27693385
TI  - Proinflammatory signals are insufficient to drive definitive hematopoietic
      specification of human HSCs in vitro.
AB  - Recent studies in zebrafish and mice have revealed that proinflammatory signaling
      is a positive regulator of definitive hematopoietic development. Whether
      proinflammatory signaling also regulates human hematopoietic specification
      remains unknown. Here, we explored the impact of the proinflammatory cytokines
      tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), and
      interleukin-1beta (IL1beta) on in vitro hematopoietic differentiation using human
      pluripotent stem cells. Gene expression analysis and enzyme-linked immunosorbent
      assay revealed the absence of a proinflammatory signature during hematopoietic
      development of human pluripotent stem cells. Functionally, the emergence of
      hemogenic endothelial progenitors (CD31+CD34+CD45- or CD34+CD43-CD73-) and
      hematopoietic cells (CD43+CD45+) was not affected by treatment with increasing
      doses of TNFalpha, IFNgamma, and IL1beta irrespective of the developmental window
      or the differentiation protocol used (embryoid body or OP9 co-culture based).
      Similarly, knockdown of endogenous NF-kB signaling had no impact on hematopoietic
      differentiation of human pluripotent stem cells. This study serves as a
      demonstration that TNFalpha, IFNgamma, and IL1beta signals do not improve
      hematopoietic differentiation of human pluripotent stem cells using current
      protocols and suggests that proinflammatory signaling is insufficient to drive
      definitive hematopoietic specification of human hematopoietic stem cells in
      vitro.

PMID- 27693387
TI  - Alterations in the bone marrow microenvironment may elicit defective
      hematopoiesis: a comparison of aplastic anemia, chronic myeloid leukemia, and
      normal bone marrow.
AB  - Hematopoiesis involves complex interactions between hematopoietic cells and the
      bone marrow (BM) microenvironment. The specific causes and mechanisms underlying
      dysregulated hematopoiesis are unknown. Here, BM biopsy specimens from patients
      with aplastic anemia (AA) and chronic myeloid leukemia (CML) and normal marrow
      were analyzed by semiquantitative immunohistochemistry to determine changes in
      the hematopoietic stem cell (HSC) compartment and BM microenvironment. HSC levels
      were lowest in AA and highest in CML. T and B lymphocytes were decreased in AA (p
      < 0.01) and CML (p < 0.01). Natural killer cells were observed in AA, but were
      absent in CML and healthy controls (p < 0.01). Macrophages and mast cells were
      absent in CML. There were significant differences between AA and CML stromal cell
      components. No nestin+ cells were observed in CML and the mean number of stromal
      cell-derived factor-1-positive cells was lowest in CML. Osteopontin+ cells were
      higher in AA than in CML (p < 0.01); osteonectin+ cells were higher in CML than
      in AA (p < 0.01). There was no significant difference in the expression of
      osteocalcin between AA and CML. The number of endothelial cells was highest in
      CML and lowest in AA (p < 0.01). Our findings suggest that changes in BM
      microenvironment components might be related to defective hematopoiesis leading
      to AA and/or CML.

PMID- 27693386
TI  - Dynamic variation of CD5 surface expression levels within individual chronic
      lymphocytic leukemia clones.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of
      clonally derived mature CD5high B cells; however, the cellular origin of CLL is
      still unknown. Patients with CLL also harbor variable numbers of CD5low B cells,
      but the clonal relationship of these cells to the bulk disease is unknown and can
      have important implications for monitoring, treating, and understanding the
      biology of CLL. Here, we use B-cell receptors (BCRs) as molecular barcodes to
      first show by single-cell BCR sequencing that the great majority of CD5low B
      cells in the blood of CLL patients are clonally related to CD5high CLL B cells.
      We investigate whether CD5 state switching was likely to occur continuously as a
      common event or as a rare event in CLL by tracking somatic BCR mutations in bulk
      CLL B cells and using them to reconstruct the phylogenetic relationships and
      evolutionary history of the CLL in four patients. Using statistical methods, we
      show that there is no parsimonious route from a single or low number of CD5low
      switch events to the CD5high population, but rather, large-scale and/or dynamic
      switching between these CD5 states is the most likely explanation. The
      overlapping BCR repertoires between CD5high and CD5low cells from CLL patient
      peripheral blood reveal that CLL exists in a continuum of CD5 expression. The
      major proportion of CD5low B cells in patients are leukemic, thus identifying
      CD5low B cells as an important component of CLL, with implications for CLL
      pathogenesis, clinical monitoring, and the development of anti-CD5-directed
      therapies.

PMID- 27693388
TI  - Clinical-grade regulatory T cells: Comparative analysis of large-scale expansion
      conditions.
AB  - Recent clinical trials have indicated the high potential of regulatory T cells
      (Tregs) in the prevention of acute and chronic graft-versus-host disease (GvHD)
      after hematopoietic stem cell transplantation, but immune interventions require
      large numbers of Tregs. With respect to their limited natural occurrence,
      development and optimization of protocols for large-scale expansion of clinical
      grade Tregs are essential if considered for therapeutic use. We compared
      different clinical-grade large-scale expansion protocols for repetitive transfer
      of large numbers of Tregs in clinical trials for the prevention of acute and/or
      chronic GvHD. Donor Tregs were isolated using magnetic-activated cell sorting
      (MACS) technology with good manufacturing practice-compliant devices. CD8 and
      CD19 depletion followed by CD25 enrichment resulted in the isolation of
      CD4+CD25+CD127- Tregs with a mean purity of 77%. Cell populations were expanded
      ex vivo using X-Vivo 15 (+/-rapamycin), TexMACS (+/-rapamycin), and CellGro DC
      (+/-rapamycin) in the presence of interleukin-2. The highest rates of expansion
      of clinical-grade Tregs were observed for X-Vivo 15 and CellGro DC without
      rapamycin in compared with all other expansion media tested. The suppressive
      capacity of the expanded Treg population was maintained under all conditions
      investigated. Our data suggest that expansion with CellGro provides data
      comparable to those obtained with TexMACS or X-Vivo 15 with rapamycin, although
      all three conditions did not provide the same propagation rate as X-Vivo 15
      alone. With respect to functionality, phenotype, and stability, CellGro DC medium
      represents a reasonable alternative for good manufacturing practice-compatible
      large-scale ex vivo expansion.

PMID- 27693389
TI  - Enzyme-linked immunosorbent assay for S100A9 in the stool of rats with dextran
      sulfate sodium-induced colitis.
AB  - Calprotectin, a heterodimer of S100A8 and S100A9, has been reported to be a
      useful biomarker in inflammatory bowel disease (IBD); however, the relationship
      between the fecal level of S100A9 and the extent of inflammation in IBD remains
      unclear. Our aim was to develop a new enzyme-linked immunosorbent assay (ELISA)
      for rat S100A9, and to investigate whether changes in fecal S100A9 levels reflect
      the inflammatory conditions in the intestinal tracts of rats with dextran sulfate
      sodium (DSS)-induced colitis. Anti-rat S100A9 monoclonal antibodies were raised
      in mice and used for the development of a novel ELISA for rat S100A9. The
      performance of our ELISA was assessed by dilution and recovery tests, and the
      detection range was 3.75-240ng/mL. The dilution test showed good linearity. The
      recovery of fecal S100A9 was 95.1% (mean), with a range of 86.1%-108.8%. Colitis
      was induced in rats by oral administration of 3% DSS/drinking water (DW) for
      11days (D group), while DW alone was provided to rats of the control group (C
      group) during the same period. The extent of inflammation was evaluated with the
      disease activity index (DAI), and the concentration of fecal S100A9 was
      determined by ELISA. Both the DAI scores and the fecal S100A9 levels were
      significantly higher in the D group than in the C group. Microscopic observation
      revealed that S100A9 was dominantly produced in many immune cells of myeloid
      origin in rat rectal tissues. These results indicate that the novel ELISA may be
      applied to clinically evaluate IBD in rats with high sensitivity. In conclusion,
      our ELISA is useful in toxicological and pharmacological evaluations.

PMID- 27693390
TI  - Effect of heavy-intensity 'priming' exercise on oxygen uptake and muscle
      deoxygenation kinetics during moderate-intensity step-transitions initiated from
      an elevated work rate.
AB  - We examined the effect of heavy-intensity 'priming' exercise on the rate of
      adjustment of pulmonary O2 uptake (tauVO2p) initiated from elevated intensities.
      Fourteen men (separated into two groups: tauVO2p<=25s [Fast] or tauVO2p>25s
      [Slow]) completed step-transitions from 20W to 45% lactate threshold (LT; lower
      step, LS) and 45% to 90%LT (upper-step, US) performed (i) without; and (ii) with
      US preceded by heavy-intensity exercise (HUS). Breath-by-breath VO2p and near
      infrared spectroscopy-derived muscle deoxygenation ([HHb+Mb]) were measured.
      Compared to LS, tauVO2p was greater (p<0.05) in US in both Fast (LS, 19+/-4s; US,
      30+/-4s) and Slow (LS, 25+/-5s; US, 40+/-11s) with tauVO2p in US being lower
      (p<0.05) in Fast. In HUS, tauVO2p in Slow was reduced (28+/-8s, p<0.05) and was
      not different (p>0.05) from LS or Fast group US. In Slow, tau[HHb+Mb] increased
      (p<0.05) in US relative to HUS; this finding coupled with a reduced tauVO2p
      indicates a priming-induced improvement in matching of muscle O2 delivery-to-O2
      utilization during transitions from elevated intensities in those with Slow but
      not Fast VO2p kinetics.

PMID- 27693392
TI  - Transgenerational impairment of hippocampal Akt-mTOR signaling and behavioral
      deficits in the offspring of mice that experience postpartum depression-like
      illness.
AB  - Postpartum depression (PPD) has adverse effects on offspring and increases their
      vulnerability to psychiatric disorders such as depression. Akt-mTOR signaling in
      the hippocampus is implicated in depression but its role in the behavioral
      deficits in PPD offspring remains unknown. By using a prepregnancy stress model
      of PPD in which Balb/c females that experience chronic stress before pregnancy
      show long-lasting PPD-like behaviors, we tested depression-like behaviors in PPD
      offspring (PPD-F1) at juvenile and adult ages as well as in the second generation
      (PPD-F2) produced by cross of male PPD-F1 with naive females. Hippocampal Akt
      mTOR signaling was examined in the F1 and F2 generations of PPD, as well as in
      PPD-F1 mice treated with a single dose of the antidepressant ketamine. PPD-F1
      showed depression-like behaviors at juvenile and adult stages, evidenced by
      reduced sucrose preference (SP), increased immobility time in the forced swim
      test (FST), and a longer latency to feed and reduced food consumption in the
      novelty suppressed feeding (NSF) test. PPD-F1 mice showed Akt-mTOR signaling
      deficiency in the hippocampus, with down-regulated expression of p-Akt, p-mTOR
      and p-p70S6K. A single dose of ketamine reversed the behavior deficits and the
      impairment in Akt-mTOR signaling in PPD-F1. Furthermore, the PPD-F2 mice remained
      deficient in the SP and NSF test and hippocampal Akt-mTOR signaling, although the
      performance in FST was normal. The present study demonstrated both long-term and
      transgenerational effects of PPD on the depression-like behaviors of offspring,
      and suggested impaired Akt-mTOR signaling may play a part.

PMID- 27693391
TI  - Replacement of serum with ocular fluid for cryopreservation of immature testes.
AB  - Cryopreservation of immature testis is a feasible approach for germplasm
      preservation of male animals. Combinations of dimethyl sulfoxide (DMSO) and
      foetal bovine serum (FBS) are used for testis cryopreservation. However, an
      alternative to FBS is needed, because FBS is expensive. Buffalo ocular fluid
      (BuOF), a slaughter house by-product, could be an economical option. The
      objective of the present study was to assess whether BuOF can replace FBS for
      cryopreservation of immature mouse (Mus musculus), rat (Rattus norvegicus), and
      buffalo (Bubalus bubalis) testes. Results showed that rodent and buffalo testes
      frozen in DMSO (10% for rodents and 20% for buffalo) with 20% FBS or BuOF had
      similar numbers of viable and DNA-damaged cells (P > 0.05). The expression of
      cell proliferation- (PCNA) and apoptosis-specific proteins (Annexin V and
      BAX/BCL2 ratio) were also comparable in mouse and buffalo testes frozen in DMSO
      with FBS or BuOF (P > 0.05). Interestingly, rat testis frozen in DMSO with BuOF
      had lower expression of Annexin V protein than testis frozen in DMSO with FBS (P
      < 0.05). The percentage of meiotic germ cells (pachytene-stage spermatocytes) in
      xenografts from testis frozen either in DMSO with BuOF or FBS did not
      significantly differ in rats or buffalo (P > 0.05). These findings provide
      evidence that BuOF has potential to replace FBS for cryopreservation of immature
      rodent and buffalo testis. Further investigation is needed to explore whether
      BuOF can replace FBS for testis cryopreservation of other species.

PMID- 27693393
TI  - Effect of exercise, exercise withdrawal, and continued regular exercise on
      excitability and long-term potentiation in the dentate gyrus of hippocampus.
AB  - Exercise mediates beneficial effects on the brain function and neural health,
      particularly in the hippocampus as the main area of memory. The hippocampus is a
      structure involved in exercise, which can improve synaptic plasticity and long
      term potentiation (LTP). The present study investigated the effect of exercise,
      exercise withdrawal, and continued regular exercise on excitability and long-term
      potentiation in the dentate gyrus (DG) of hippocampus. Fifty male Wistar rats
      were randomly allocated to the five control, sham, exercise, exercise withdrawal,
      and continued regular exercise treatments. The experimental animals were forced
      to run on a treadmill one hour a day at a speed of 20-21m/min over the two
      experimental periods of 21 and 42 days. While stimulating the medial perforant
      pathway, input-output (I/O) functions and LTP were recorded from the DG to
      evaluate synaptic potency and plasticity. The relevant responses in the DG were
      evaluated in all the groups from the slope and PS amplitude of the fEPSP. Results
      showed that the 21-day exercise treatment increased both the responsiveness and
      LTP in the DG of hippocampus. A 21-day withdrawal period after the exercise
      impaired the beneficial effects of the exercise, indicating the reversibility of
      these exercise-related hippocampal changes. Significant enhancements were also
      observed in cell responsiveness and LTP with the continued regular exercise (42
      day) treatment.

PMID- 27693394
TI  - Central mechanism of the cardiovascular responses caused by L-proline
      microinjected into the paraventricular nucleus of the hypothalamus in
      unanesthetized rats.
AB  - Previously, we reported that microinjection of L-proline (L-Pro) into the
      paraventricular nucleus of the hypothalamus (PVN) caused vasopressin-mediated
      pressor responses in unanesthetized rats. In the present study, we report on the
      central mechanisms involved in the mediation of the cardiovascular effects caused
      by the microinjection of L-Pro into the PVN. Microinjection of increasing doses
      of L-Pro (3-100nmol/100nL) into the PVN caused dose-related pressor and
      bradycardic responses. No cardiovascular responses were observed after the
      microinjection of equimolar doses (33nmol/100nL) of its isomer D-Proline (D-Pro)
      or Mannitol. The PVN pretreatment with either a selective non-NMDA (NBQX) or
      selective NMDA (LY235959 or DL-AP7) glutamate receptor antagonists blocked the
      cardiovascular response to L-Pro (33nmol/100nL). The dose-effect curve for the
      pretreatment with increasing doses of LY235959 was located at the left in
      relation to the curves for NBQX and DL-AP7, showing that LY235959 is more potent
      than NBQX, which is more potent than DL-AP7 in inhibiting the cardiovascular
      response to L-Pro. The cardiovascular response to the microinjection of L-Pro
      into the PVN was not affected by local pretreatment with Nomega-Propyl-l-arginine
      (N-Propyl), a selective inhibitor of the neuronal nitric oxide synthase (nNOS),
      suggesting that NO does not mediate the responses to L-Pro in the PVN. In
      conclusion, the results suggest that ionotropic receptors in the PVN, blocked by
      both NMDA and non-NMDA receptor antagonists, mediate the pressor response to L
      Pro that results from activation of PVN vasopressinergic magnocellular neurons
      and vasopressin release into the systemic circulation.

PMID- 27693395
TI  - MiR-195 dependent roles of mitofusin2 in the mitochondrial dysfunction of
      hippocampal neurons in SAMP8 mice.
AB  - Abnormal gene expression, including mRNAs, and microRNAs (miRNA), have been
      identified in the development of Alzheimer's disease (AD). Although mitofusin2
      (mfn2) has been found to be down-regulated in the neurons from hippocampus and
      cortex in AD patients, little is known about its roles and the regulatory
      mechanisms in the pathogenesis of AD. This study was performed to investigate the
      roles of mfn2 protein and its upstream regulatory mechanism in the progression of
      AD using a senescence accelerated mouse prone-8 (SAMP8) model. The results of
      quantitative real-time PCR and western blot revealed that mfn2 expression
      displayed a consistent decrease with aging in the hippocampus of SAMP8 than did
      age-matched SAMR1 mice. The luciferase activity assay combined with mutational
      analysis confirmed the binding site of miR-195 to the 3' -untranslated region (3'
      UTR) of mfn2 mRNA. Furthermore, miR-195 inhibitor or antigomir induced the higher
      level expression of mfn2 protein in vitro and in vivo. In addition, exogenous
      expression of miR-195 decreased the mitochondrial membrane potential (MMP) of the
      HT-22 cells by targeting mfn2. In conclusion, these results indicated that
      deregulation of mfn2 might be involved in mitochondrial dysfunction during the
      progression of AD, and its decreased expression was regulated at least in part by
      miR-195 in AD mice. The abnormal expression of miR-195 played a potential role in
      mitochondrial disorder by targeting mfn2 in hippocampus of SAMP8 mice. Therefore,
      upregulation of mfn2 protein by inhibiting miR-195 might be a potential new
      therapeutic strategy for treatment of AD.

PMID- 27693398
TI  - Cell fate regulation by chromatin ADP-ribosylation.
AB  - ADP-ribosylation is an evolutionarily conserved complex posttranslational
      modification that alters protein function and/or interaction. Intracellularly, it
      is mainly catalyzed by diphtheria toxin-like ADP-ribosyltransferases (ARTDs),
      which attach one or several ADP-ribose residues onto target proteins. Several
      specific mono- and poly-ADP-ribosylation binding modules exist; hydrolases
      reverse the modification. The best-characterized ARTD family member, ARTD1,
      regulates various DNA-associated processes. Here, we focus on the role of ARTD1
      mediated chromatin ADP-ribosylation in development, differentiation, and
      pluripotency, and the recent development of new methodologies that will enable
      more insight into these processes.

PMID- 27693396
TI  - Functional connectivity patterns of normal human swallowing: difference among
      various viscosity swallows in normal and chin-tuck head positions.
AB  - Consuming thicker fluids and swallowing in the chin-tuck position has been shown
      to be advantageous for some patients with neurogenic dysphagia who aspirate due
      to various causes. The anatomical changes caused by these therapeutic techniques
      are well known, but it is unclear whether these changes alter the cerebral
      processing of swallow-related sensorimotor activity. We sought to investigate the
      effect of increased fluid viscosity and chin-down posture during swallowing on
      brain networks. 55 healthy adults performed water, nectar-thick, and honey thick
      liquid swallows in the neutral and chin-tuck positions while EEG signals were
      recorded. After pre-processing of the EEG timeseries, the time-frequency based
      synchrony measure was used for forming the brain networks to investigate whether
      there were differences among the brain networks between the swallowing of
      different fluid viscosities and swallowing in different head positions. We also
      investigated whether swallowing under various conditions exhibit small-world
      properties. Results showed that fluid viscosity affects the brain network in the
      Delta, Theta, Alpha, Beta, and Gamma frequency bands and that swallowing in the
      chin-tuck head position affects brain networks in the Alpha, Beta, and Gamma
      frequency bands. In addition, we showed that swallowing in all tested conditions
      exhibited small-world properties. Therefore, fluid viscosity and head positions
      should be considered in future swallowing EEG investigations.

PMID- 27693397
TI  - Selective CRF2 receptor agonists ameliorate the anxiety- and depression-like
      state developed during chronic nicotine treatment and consequent acute withdrawal
      in mice.
AB  - The aim of the present study was to investigate the effects of the selective
      agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN
      2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by
      acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed
      for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline
      solution and 1day of acute withdrawal and then a single intracerebroventricular
      (ICV) injection with UCN 2, UCN 3 or saline solution. After 30min the mice were
      observed in an elevated plus-maze test or a forced swim test, for anxiety- and
      depression-like behavior. After 5min of testing, the plasma corticosterone
      concentration reflecting the activity of the hypothalamic-pituitary-adrenal (HPA)
      axis was also determined by a chemo-fluorescent method. Half of the animals were
      treated ICV and evaluated on the 8th day, the other half on the 9th day. On the
      8th day, nicotine-treated mice presented signs of anxiolysis and depression, but
      no significant elevation of the plasma corticosterone concentration. On the 9th
      day, nicotine-treated mice exhibited signs of anxiety and depression and a
      significant increase of the plasma corticosterone levels. Central administration
      of UCN 2 or UCN 3 ameliorated the anxiety- and depression-like state including
      the hyperactivity of the HPA axis, developed during acute withdrawal following
      chronic nicotine treatment. The present study suggests that selective CRF2
      receptor agonists could be used as a therapy in nicotine addiction.

PMID- 27693399
TI  - Opening the Effector Protein Toolbox for Plant-Parasitic Cyst Nematode
      Interactions.

PMID- 27693400
TI  - Spatial and temporal heterogeneity of infectious hematopoietic necrosis virus in
      Pacific Northwest salmonids.
AB  - The aquatic rhaboviral pathogen infectious hematopoietic necrosis virus (IHNV)
      causes acute disease in juvenile fish of a number of populations of Pacific
      salmonid species. Heavily managed in both marine and freshwater environments,
      these fish species are cultured during the juvenile stage in freshwater
      conservation hatcheries, where IHNV is one of the top three infectious diseases
      that cause serious morbidity and mortality. Therefore, a comprehensive study of
      viral genetic surveillance data representing 2590 field isolates collected
      between 1958 and 2014 was conducted to determine the spatial and temporal
      patterns of IHNV in the Pacific Northwest of the contiguous United States.
      Prevalence of infection varied over time, fluctuating over a rough 5-7yearcycle.
      The genetic analysis revealed numerous subgroups of IHNV, each of which exhibited
      spatial heterogeneity. Within all subgroups, dominant genetic types were
      apparent, though the temporal patterns of emergence of these types varied among
      subgroups. Finally, the affinity or fidelity of subgroups to specific host
      species also varied, where UC subgroup viruses exhibited a more generalist
      profile and all other subgroups exhibited a specialist profile. These complex
      patterns are likely synergistically driven by numerous ecological,
      pathobiological, and anthropogenic factors. Since only a few anthropogenic
      factors are candidates for managed intervention aimed at improving the health of
      threatened or endangered salmonid fish populations, determining the relative
      impact of these factors is a high priority for future studies.

PMID- 27693402
TI  - MicroRNAs play big roles in modulating macrophages response toward mycobacteria
      infection.
AB  - Macrophages are crucial player in the defense against multiple intracellular
      pathogens. Mycobacterium tuberculosis, the causative agent of tuberculosis which
      inflicted around one third of global population, can replicate and persist within
      macrophages. MicroRNAs, endogenous, small noncoding RNA, can regulate the
      expression of macrophages genes required for appropriate signaling. Mycobacteria
      can manipulate the expression of macrophages microRNAs to subvert cell response
      for its survival and persistence. This review summarized the progress of
      microRNAs in mycobacterial pathogenesis.

PMID- 27693401
TI  - Microgeographically diverse Plasmodium vivax populations at the Thai-Myanmar
      border.
AB  - Malaria transmission along international borders of the Greater Mekong Subregion
      is a big challenge for regional malaria elimination. At the Thai-Myanmar border,
      Plasmodium falciparum cases have dropped dramatically; however, increasing P.
      vivax prevalence and the emerging reports on hidden malaria burden due to
      asymptomatic infections demand attention. We conducted cross-sectional surveys to
      detect asymptomatic malaria infections in a small village located at Thai-Myanmar
      border and genotyped P. vivax infections in order to understand the level of
      genetic diversity on such a microgeographic scale. PCR/RFLP and DNA sequencing
      identified high levels of genetic polymorphisms at both Pvmsp3alpha and
      Pvmsp3beta loci among P. vivax infections. Combining the PCR/RFLP patterns of
      Pvmsp3alpha and Pvmsp3beta, a total of 10 genotypes were observed among 17
      samples, while concatenated DNA sequences of Pvmsp3alpha and 3beta generated 14
      haplotypes with haplotype diversity of 0.97. These markedly diverse parasites on
      a microgeographic scale suggest the circulation of a considerably large parasite
      population at the international border.

PMID- 27693404
TI  - Therapeutic Effect of Virtual Reality on Post-Stroke Patients: Randomized
      Clinical Trial.
AB  - OBJECTIVES: The study aimed to check the therapeutic effect of virtual reality
      associated with conventional physiotherapy on gait balance and the occurrence of
      falls after a stroke. METHODS: This was a randomized, blinded clinical trial
      conducted with post-stroke patients, randomized into two groups-treatment group
      and control group-and subjected to balance assessments by the Dynamic Gait Index
      and investigation of falls before and after 20 intervention sessions.
      Statistically significant difference was considered at P < .05. RESULTS: We
      selected 30 patients, but there were three segment losses, resulting in a total
      of 13 patients in the control group and 14 in the treatment group. There was an
      improvement in gait balance and reduced occurrence of falls in both groups. After
      intervention, the differences in gait balance in the control group (P = .047) and
      the reduction in the occurrence of falls in the treatment group (P = .049) were
      significant. However, in intergroup analysis, there was no difference in the two
      outcomes. CONCLUSIONS: Therapy with games was a useful tool for gait balance
      rehabilitation in post-stroke patients, with repercussions on the reduction of
      falls.

PMID- 27693403
TI  - Imaging the Transformation of Ipsilateral Internal Capsule Following Focal
      Cerebral Ischemia in Rat by Diffusion Kurtosis Imaging.
AB  - BACKGROUND: The purpose of our study is to explore the relationship between
      recovery of neural function and transformation of the internal capsule (IC) after
      transient middle cerebral artery occlusion (MCAO) by using diffusion kurtosis
      imaging (DKI). METHODS: Six male adult Sprague-Dawley rats implemented with
      transient MCAO were used in this study. Sensorimotor function was assessed
      according to repetitive behavioral testing on day 1, 3, 7, 14, and 28 after
      cerebral ischemia. Metrics of DKI were acquired, and the time course of the
      region-to-normal ratio was evaluated in IC. RESULTS: After cerebral ischemia,
      relative fractional anisotropy in IC decreased on day 3 (P < .01). Relative mean
      diffusivity (rMD) increased on day 28 (P < .05). Relative mean diffusional
      kurtosis (rMK) increased on day 3 (P < .01) and decreased on day 7 (P < .05).
      Relative axial diffusional kurtosis (rKa) increased on day 3 (P < .01) and
      declined on day 7 (P < .05). Relative radial diffusional kurtosis (rKr) was
      reduced on day 7 (P < .05). Changes in rMK were larger than changes in rMD on day
      3 (P < .05). The factor of rKa and rKr revealed marked difference on day 7 (P <
      .05) and day 14 (P < .05). Neurological function score showed that rats exhibited
      functional recovery from day 7 (P < .01) post stroke. CONCLUSIONS: This
      longitudinal multiparametric magnetic resonance imaging study suggested that K
      metrics offers information complimentary to conventional diffusion metrics and
      revealed the procedure during the structural modification in the ipsilateral IC
      following focal cerebral ischemia. After transient MCAO, the neural
      transformation occurred in a time-dependent procedure.

PMID- 27693405
TI  - The role of post-translational protein modifications on heart and vascular
      metabolism.

PMID- 27693406
TI  - Reveal the molecular signatures of hepatocellular carcinoma with different sizes
      by iTRAQ based quantitative proteomics.
AB  - : Tumor size of hepatocellular carcinoma (HCC) is a key parameter for predicting
      prognosis of HCC patients. The biological behaviors of HCC, such as tumor growth,
      recurrence and metastasis are significantly associated with tumor size. However,
      the underlying molecular mechanisms remain unclear. Here, we applied iTRAQ-based
      proteomic strategy to analyze the proteome differences among small, media, large
      and huge primary HCC tissues. In brief,88 proteins in small HCC, 69 proteins in
      media HCC, 118 proteins in large HCC and 215 proteins in huge HCC, were
      identified by comparing the proteome of cancerous tissues with its corresponding
      non-cancerous tissues. Further analysis of dysregulated proteins involved in
      signaling revealed that alteration of ERK1/2 and AKT signaling played important
      roles in the tumorigenesis or tumor growth in all subtypes. Interestingly,
      alteration of specific signaling was discovered in small and huge HCC, which
      might reflect specific molecular mechanisms of tumor growth. Furthermore, the
      dysregulation degree of a group of proteins has been confirmed to be
      significantly correlated with the tumor size; these proteins might be potential
      targets for studying tumor growth of HCC. Overall, we have revealed the molecular
      signatures of HCC with different tumor sizes, and provided fundamental
      information for further in-depth study. BIOLOGICAL SIGNIFICANCE: In this study,
      we compared the protein expression profiles among different HCC subtypes,
      including small HCC, media HCC, large HCC and huge HCC for the first time. The
      results clearly proved that different molecular alterations and specific
      signaling pathways were indeed involved in different HCC subtypes, which might
      explain the different malignancy biological behaviors. In addition, the
      dysregulation degree of a group of proteins has been confirmed to be
      significantly correlated with the tumor size. We believe that these findings
      would help us better understand the underlying molecular mechanisms of the
      tumorigenesis and development of HCC.

PMID- 27693407
TI  - The pUltra plasmid series: A robust and flexible tool for fluorescent labeling of
      Enterobacteria.
AB  - Fluorescent labeling has been an invaluable tool for the study of living
      organisms and bacterial species are no exception to this. Here we present and
      characterize the pUltra plasmids which express constitutively a fluorescent
      protein gene (GFP, RFP, YFP or CFP) from a strong synthetic promoter and are
      suitable for the fluorescent labeling of a broad range of Enterobacteria. The
      amount of expressed fluorophore from these genetic constructs is such, that the
      contours of the cells can be delineated on the basis of the fluorescent signal
      only. In addition, labeling through the pUltra plasmids can be used successfully
      for fluorescence and confocal microscopy while unambiguous distinction of cells
      labeled with different colors can be carried out efficiently by microscopy or
      flow cytometry. We compare the labeling provided by the pUltra plasmids with that
      of another plasmid series encoding fluorescent proteins and we show that the
      pUltra constructs are vastly superior in signal intensity and discrimination
      power without having any detectable growth rate effects for the bacterial
      population. We also use the pUltra plasmids to produce mixtures of differentially
      labeled pathogenic Escherichia, Shigella and Salmonella species which we test
      during infection of mammalian cells. We find that even inside the host cell,
      different strains can be distinguished effortlessly based on their fluorescence.
      We, therefore, conclude that the pUltra plasmids are a powerful labeling tool
      especially useful for complex biological experiments such as the visualization of
      ecosystems of different bacterial species or of enteric pathogens in contact with
      their hosts.

PMID- 27693408
TI  - Lung volume reduction for emphysema.
AB  - Advanced emphysema is a lung disease in which alveolar capillary units are
      destroyed and supporting tissue is lost. The combined effect of reduced gas
      exchange and changes in airway dynamics impairs expiratory airflow and leads to
      progressive air trapping. Pharmacological therapies have limited effects.
      Surgical resection of the most destroyed sections of the lung can improve
      pulmonary function and exercise capacity but its benefit is tempered by
      significant morbidity. This issue stimulated a search for novel approaches to
      lung volume reduction. Alternative minimally invasive approaches using
      bronchoscopic techniques including valves, coils, vapour thermal ablation, and
      sclerosant agents have been at the forefront of these developments. Insertion of
      endobronchial valves in selected patients could have benefits that are comparable
      with lung volume reduction surgery. Endobronchial coils might have a role in the
      treatment of patients with emphysema with severe hyperinflation and less
      parenchymal destruction. Use of vapour thermal energy or a sclerosant might allow
      focal treatment but the unpredictability of the inflammatory response limits
      their current use. In this Review, we aim to summarise clinical trial evidence on
      lung volume reduction and provide guidance on patient selection for available
      therapies.

PMID- 27693409
TI  - Serum Paraoxonase activity in relation to lipid profile in Age-related Macular
      Degeneration patients.
AB  - Age-related Macular Degeneration (AMD) is a multifactorial disease causing visual
      impairment in old age. Oxidative stress is one of the main contributors for the
      disease progression. Paraoxonase (PON), a HDL-resident antioxidant enzyme which
      removes oxidized low density lipoprotein (oxLDL), which is not studied much in
      AMD. This study assesses the PON activities in relation to the lipid status and
      genetic variants in AMD patients. In this prospective case-control study, a total
      of 48 AMD patients and 30 unrelated healthy controls were recruited. The serum
      oxLDL and Plasma Homocysteine (Hcy) levels were estimated by ELISA. Plasma
      Homocysteine thiolactone (HCTL) was estimated by HPLC. Serum PON activities were
      estimated by spectrophotometry. PON gene expression was assessed by qPCR and
      protein expression by western blot, immunofluorescence and FACS analysis. Two
      known single nucleotide polymorphisms (SNPs) in the coding region of PON1, Q192R
      and L55M variants were checked in the AMD patients and controls and their
      association with PON activity and lipid levels were determined. Serum paraoxonase
      (PONase) and thiolactonase (PON-HCTLase) activities were significantly elevated
      in AMD patients than in controls apart from elevated serum levels of total
      cholesterol (TC), triglycerides (TG), oxLDL. While serum LDL levels in AMD
      patients correlate positively with PON HCTLase activity, the serum high density
      lipoprotein (HDL) correlates with both PONase and PON-HCTLase activities.
      However, multiple regression analysis showed that, amongst the parameters, only
      serum TG was a significant risk factor for AMD, after adjusting for demographic
      parameters as well as cataract. PON2 was significantly increased at the level of
      gene expression (p = 0.03) as seen in circulating peripheral blood mononuclear
      cells (PBMC) of AMD patients possibly mediated by the transcription factor SP1,
      that showed 2-fold increase. PON1 and 2 protein expressions also showed
      significant increase in the PBMC of AMD patients. At serum level, PON1 protein
      was significantly increased in AMD patients. Cholesterol transporters such as
      CD36, SR-B1 and ABCA1 gene expressions were also found to be higher (1.5, 1.9 and
      2.4-fold respectively) in AMD, though not statistically significant. While the
      wet AMD (CNV) was found to be associated with increase in oxLDL and serum PONase
      activity, the dry AMD was associated with increased HDL and serum PON-HCTLase
      activity. The genotype and allele frequencies of Q192R & L55M were not
      significantly different between AMD patients and controls. However, altered lipid
      status and PON activities were associated with the genotype in AMD patients. A
      higher enzyme activity was observed for the RR genotype of Q192R in the cohort,
      irrespective of case and control. Thus the PON genotype and phenotype seem to
      play a role in the pathogenesis of AMD.

PMID- 27693411
TI  - Corrigendum to "Seven novel genetic mutations within the 5' UTR and the
      housekeeping promoter of HMBS gene responsible for the non-erythroid form of
      acute intermittent porphyria" [Blood Cells Mol. Dis. 49 (2012) 147-151].

PMID- 27693412
TI  - Autocratic strategies for alternating games.
AB  - Repeated games have a long tradition in the behavioral sciences and evolutionary
      biology. Recently, strategies were discovered that permit an unprecedented level
      of control over repeated interactions by enabling a player to unilaterally
      enforce linear constraints on payoffs. Here, we extend this theory of "zero
      determinant" (or, more generally, "autocratic") strategies to alternating games,
      which are often biologically more relevant than traditional synchronous games.
      Alternating games naturally result in asymmetries between players because the
      first move matters or because players might not move with equal probabilities. In
      a strictly-alternating game with two players, X and Y, we give conditions for the
      existence of autocratic strategies for player X when (i) X moves first and (ii) Y
      moves first. Furthermore, we show that autocratic strategies exist even for (iii)
      games with randomly-alternating moves. Particularly important categories of
      autocratic strategies are extortionate and generous strategies, which enforce
      unfavorable and favorable outcomes for the opponent, respectively. We illustrate
      these strategies using the continuous Donation Game, in which a player pays a
      cost to provide a benefit to the opponent according to a continuous cooperative
      investment level. Asymmetries due to alternating moves could easily arise from
      dominance hierarchies, and we show that they can endow subordinate players with
      more autocratic strategies than dominant players.

PMID- 27693410
TI  - An important role for adenine, cholera toxin, hydrocortisone and triiodothyronine
      in the proliferation, self-renewal and differentiation of limbal stem cells in
      vitro.
AB  - The cornea is a self-renewing tissue located at the front of the eye. Its
      transparency is essential for allowing light to focus onto the retina for visual
      perception. The continuous renewal of corneal epithelium is supported by limbal
      stem cells (LSCs) which are located in the border region between conjunctiva and
      cornea known as the limbus. Ex vivo expansion of LSCs has been successfully
      applied in the last two decades to treat patients with limbal stem cell
      deficiency (LSCD). Various methods have been used for their expansion, yet the
      most widely used culture media contains a number of ingredients derived from
      animal sources which may compromise the safety profile of human LSC
      transplantation. In this study we sought to understand the role of these
      components namely adenine, cholera toxin, hydrocortisone and triiodothyronine
      with the aim of re-defining a safe and GMP compatible minimal media for the ex
      vivo expansion of LSCs on human amniotic membrane. Our data suggest that all four
      components play a critical role in maintaining LSC proliferation and promoting
      LSC self-renewal. However removal of adenine and triiodothyronine had a more
      profound impact and led to LSC differentiation and loss of viability
      respectively, suggesting their essential role for ex vivo expansion of LSCs.
      Replacement of each of the components with GMP-grade reagents resulted in equal
      growth to non-GMP grade media, however an enhanced differentiation of LSCs was
      observed, suggesting that additional combinations of GMP grade reagents need to
      be tested to achieve similar or better level of LSC maintenance in the same
      manner as the traditional LSC media.

PMID- 27693413
TI  - Levetiracetam treatment influences blood-brain barrier failure associated with
      angiogenesis and inflammatory responses in the acute phase of epileptogenesis in
      post-status epilepticus mice.
AB  - Our previous study showed that treatment with levetiracetam (LEV) after status
      epilepticus (SE) termination by diazepam might prevent the development of
      spontaneous recurrent seizures via the inhibition of neurotoxicity induced by
      brain edema events. In the present study, we determined the possible molecular
      and cellular mechanisms of LEV treatment after termination of SE. To assess the
      effect of LEV against the brain alterations after SE, we focused on blood-brain
      barrier (BBB) dysfunction associated with angiogenesis and brain inflammation.
      The consecutive treatment of LEV inhibited the temporarily increased BBB leakage
      in the hippocampus two days after SE. At the same time point, the LEV treatment
      significantly inhibited the increase in the number of CD31-positive endothelial
      immature cells and in the expression of angiogenic factors. These findings
      suggested that the increase in neovascularization led to an increase in BBB
      permeability by SE-induced BBB failure, and these brain alterations were
      prevented by LEV treatment. Furthermore, in the acute phase of the latent period,
      pro-inflammatory responses for epileptogenic targets in microglia and astrocytes
      of the hippocampus activated, and these upregulations of pro-inflammatory-related
      molecules were inhibited by LEV treatment. These findings suggest that LEV is
      likely involved in neuroprotection via anti-angiogenesis and anti-inflammatory
      activities against BBB dysfunction in the acute phase of epileptogenesis after
      SE.

PMID- 27693414
TI  - Increased striatal VMAT2 binding in mice after chronic administration of
      methcathinone and manganese.
AB  - Intravenous use of a psychostimulant drug containing methcathinone (ephedrone)
      and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We
      aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6
      mice were intraperitoneally injected once a day with the study drug or saline for
      a period of 27 weeks. Motor activity was recorded in an automated motility-box.
      After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed
      using [11C]dihydrotetrabenazine ([11C]DTBZ). After 27 weeks of treatment
      [11C]DTBZ autoradiography demonstrated a significant increase in the striatum-to
      cerebellum binding ratio compared with saline treated controls. At the same time
      point, there was no evident change in motor activity. Increased [11C]DTBZ binding
      may indicate vesicular monoamine transporter type 2 (VMAT2) function is altered.
      The lack of extrapyramidal symptoms in animals could be attributed to low dosing
      regimen or high metabolic rate.

PMID- 27693415
TI  - Altered melatonin MT1 receptor expression in the ventral midbrain following 6
      hydroxydopamine lesions in the rat medial forebrain bundle.
AB  - The indoleamine hormone melatonin protects dopamine neurons in the rat
      nigrostriatal pathway following 6-hydroxydopamine lesioning, and an increase in
      striatal melatonin levels has been detected in this model of Parkinson's disease.
      Melatonin induces the expression of tyrosine hydroxylase, the rate-limiting
      enzyme for dopamine synthesis, in the ventral midbrain, where G protein-coupled
      melatonin receptors are present. Based on the interaction between the
      melatonergic and dopaminergic systems, we hypothesized that 6-hydroxydopamine
      induced degeneration of dopamine neurons would affect the expression of melatonin
      receptors in the nigrostriatal pathway. Following unilateral injection of 6
      hydroxydopamine into the rat striatum or medial forebrain bundle, there was a
      significant increase in apomorphine-induced contralateral rotations in lesioned
      animals as compared to sham controls. A loss of tyrosine hydroxylase
      immunoreactivity and/or immunofluorescence in the striatum and substantia nigra
      was seen in animals lesioned in either the striatum or medial forebrain bundle,
      indicating degeneration of dopamine neurons. There were no significant
      differences in melatonin MT1 receptor protein expression in the striatum or
      substantia nigra, between intrastriatally lesioned animals and sham controls. In
      contrast, lesions in the medial forebrain bundle caused a significant increase in
      MT1 receptor mRNA expression (p<0.03) on the lesioned side of the ventral
      midbrain, as compared with the contralateral side. Given the presence of MT1
      receptors on neurons in the ventral midbrain, these results suggest that a
      compensatory increase in MT1 transcription occurs to maintain expression of this
      receptor and neuroprotective melatonergic signaling in the injured brain.

PMID- 27693416
TI  - Sulforaphane activates the cerebral vascular Nrf2-ARE pathway and suppresses
      inflammation to attenuate cerebral vasospasm in rat with subarachnoid hemorrhage.
AB  - Nrf2-ARE pathway reportedly plays a protective role in several central nervous
      system diseases. No study has explored the role of the Nrf2-ARE pathway in
      cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the
      present study was to investigate the activation of the cerebral vascular Nrf2-ARE
      pathway and to determine the potential role of this pathway in the development of
      CVS following SAH. We investigated whether the administration of sulforaphane
      (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway
      activity, proinflammatory cytokine expression, and clinical behavior in a rat
      model of SAH. A two-hemorrhage protocol was used to generate an animal model of
      SAH in male Sprague-Dawley rats. Administration of SFN to these rats following
      SAH enhanced the activity of the Nrf2-ARE pathway and suppressed the release of
      proinflammatory cytokines. Vasospasm was markedly attenuated in the basilar
      arteries after SFN therapy. Additionally, SFN administration significantly
      ameliorated two behavioral functions disrupted by SAH. These results suggest that
      SFN has a therapeutic benefit in post-SAH, and this may be due to elevated Nrf2
      ARE pathway activity and inhibition of cerebral vascular proinflammatory cytokine
      expression.

PMID- 27693418
TI  - Tumour-necrosis factor-alpha induces heparan sulfate 6-O-endosulfatase 1 (Sulf-1)
      expression in fibroblasts.
AB  - Heparan sulfate (HS) 6-O-endosulfatases (Sulfs) have emerged recently as critical
      regulators of many physiological and pathological processes. By removing 6-O
      sulfates from specific HS sequences, they modulate the activities of a variety of
      growth factors and morphogens, including fibroblast growth factor (FGF)-1.
      However, little is known about the functions of Sulfs in inflammation. Tumour
      necrosis factor (TNF)-alpha plays an important role in regulating the behaviour
      of fibroblasts. In this study, we examined the effect of this inflammatory
      cytokine on the expression of Sulfs in human MRC-5 fibroblasts. Compositional
      analysis of HS from TNF-alpha-treated cells showed a strong reduction in the
      amount of the trisulfated UA2S-GlcNS6S disaccharide, which suggested a selective
      reaction of 6-O-desulfation. Real-time PCR analysis revealed that TNF-alpha
      increased Sulf-1 expression in a dose- and time-dependent manner, via a mechanism
      involving NF-KB, ERK1/2 and p38 MAPK. In addition, we confirmed that cell
      stimulation with TNF-alpha was accompanied by the secretion of an active form of
      Sulf-1. To study the function of Sulf- 1, we examined the responses induced by
      FGF-1. We showed that ERK1/2 activation and cell proliferation were markedly
      reduced in TNF-alpha-treated MRC-5 cells compared with untreated cells. Silencing
      the expression of Sulf-1 by RNA interference restored the responses induced by
      FGF-1, which indicated that TNF-alpha-mediated induction of the sulfatase indeed
      resulted in alterations of HS biological properties. Taken together, our results
      indicate that Sulf-1 is responsive to TNF-alpha stimulation and may function as
      an autocrine regulator of fibroblast expansion in the course of an inflammatory
      response.

PMID- 27693417
TI  - Phenotypes associated with psychiatric disorders are sex-specific in a mutant
      mouse line.
AB  - Wnt1-Cre- and Wnt1-GAL4 double transgenic (dTg) mice are used to study neural
      crest cell lineages by utilizing either the Cre/loxP or the GAL4/UAS system. We
      have previously shown that these mice exhibit behavioral abnormalities that
      resemble certain behaviors of psychiatric disorders and histologic alterations in
      the cholinergic and glutamatergic systems in the brain. The objective of the
      current study was to extend the behavioral analyses in these mice and to
      determine whether there were any sex-specific differences in the prevalence or
      severity of these behaviors. In the present study, we demonstrate additional
      behavioral abnormalities in dTg mice, such as increased locomotor activity,
      decreased social behavior, and an increased frequency in vertical jumping. Of
      these, the proclivity for vertical jumping was observed only in male dTg mice. In
      contrast, MK-801 administration induced increased locomotion in only female dTg
      mice. Furthermore, the concentrations of prolactin in the sera and oxytocin in
      the hypothalamus were both reduced only in female dTg mice, compared to controls.
      These sex-dependent behavioral and hormonal abnormalities in the dTG mice suggest
      that the phenotype of certain psychiatric disorders may be influenced by both
      genetic and sex-specific factors.

PMID- 27693419
TI  - Hypothalamic regulation of body growth and appetite by ghrelin-derived peptides
      during balanced nutrition or undernutrition.
AB  - Among the gastrointestinal hormones that regulate food intake and energy
      homeostasis, ghrelin plays a unique role as the first one identified to increases
      appetite and stimulate GH secretion. This review highlights the latest mechanism
      by which ghrelin modulates body growth, appetite and energy metabolism by
      exploring pharmacological actions of the hormone and consequences of genetic or
      pharmacological blockade of the ghrelin/GHS-R (Growth Hormone Secretagogue
      Receptor) system on physiological responses in specific nutritional situations.
      Within the hypothalamus, novel mechanisms of action of this hormone involve its
      interaction with other ghrelin-derived peptides, such as desacyl ghrelin and
      obestatin, which are thought to act as functional ghrelin antagonists, and
      possible modulation of the GHS-R with other G-protein coupled receptors. During
      chronic undernutrition such as anorexia nervosa, variations of ghrelin-derived
      peptides may be an adaptative metabolic response to maintain normal glycemic
      control. Interestingly, some of ghrelin's metabolic actions are thought to be
      relayed through modulation of GH, an anabolic and hyperglycemic agent.

PMID- 27693420
TI  - Association Between 6-Minute Walk Test Distance and Objective Variables of
      Functional Capacity After Exercise Training in Elderly Heart Failure Patients
      With Preserved Ejection Fraction: A Randomized Exercise Trial.
AB  - OBJECTIVE: To evaluate the change in the 6-minute walk test (6-MWT) distance
      relative to changes in key functional capacity measures after 16 weeks of
      exercise training in older patients (>=65y) who have heart failure with preserved
      ejection fraction (HFpEF). DESIGN: Prospective, randomized, single-blinded (by
      researchers to patient group) comparison of 2 groups of HFpEF patients. SETTING:
      Hospital and clinic records; ambulatory outpatients. PARTICIPANTS: Participants
      (N=47) randomly assigned to an attention control (AC) (n=24) or exercise training
      (ET) (n=23) group. INTERVENTION: The ET group performed cycling and walking at
      50% to 70% of peak oxygen uptake (Vo2peak) intensity (3d/wk, 60min each session).
      MAIN OUTCOME MEASURES: Vo2peak, ventilatory threshold (VT), and 6-MWT distance
      were measured at baseline and after the 16-week study period. RESULTS: At follow
      up, the 6-MWT distance was higher than at the baseline in both the ET (11%,
      P=.005) and AC (9%, P=.004) groups. In contrast, Vo2peak and VT values increased
      in the ET group (19% and 11%, respectively; P=.001), but decreased in the AC
      group at follow-up (2% and 0%, respectively). The change in Vo2peak versus 6-MWT
      distance after training was also not significantly correlated in the AC group
      (r=.01, P=.95) or in the ET group (r=.13, P=.57). The change in 6-MWT distance
      and VT (an objective submaximal exercise measure) was also not significantly
      correlated in the AC group (r=.08, P=.74) or in the ET group (r=.16, P=.50).
      CONCLUSIONS: The results of this study challenge the validity of using the 6-MWT
      as a serial measure of exercise tolerance in elderly HFpEF patients and suggest
      that submaximal and peak exercise should be determined objectively by VT and
      Vo2peak in this patient population.

PMID- 27693421
TI  - Feasibility of a Smartphone-Based Exercise Program for Office Workers With Neck
      Pain: An Individualized Approach Using a Self-Classification Algorithm.
AB  - OBJECTIVE: To explore the feasibility of a newly developed smartphone-based
      exercise program with an embedded self-classification algorithm for office
      workers with neck pain, by examining its effect on the pain intensity, functional
      disability, quality of life, fear avoidance, and cervical range of motion (ROM).
      DESIGN: Single-group, repeated-measures design. SETTING: The laboratory and
      participants' home and work environments. PARTICIPANTS: Offices workers with neck
      pain (N=23; mean age +/- SD, 28.13+/-2.97y; 13 men). INTERVENTION: Participants
      were classified as having 1 of 4 types of neck pain through a self-classification
      algorithm implemented as a smartphone application, and conducted corresponding
      exercise programs for 10 to 12min/d, 3d/wk, for 8 weeks. MAIN OUTCOME MEASURES:
      The visual analog scale (VAS), Neck Disability Index (NDI), Medical Outcomes
      Study 36-Item Short-Form Health Survey (SF-36), Fear-Avoidance Beliefs
      Questionnaire (FABQ), and cervical ROM were measured at baseline and
      postintervention. RESULTS: The VAS (P<.001) and NDI score (P<.001) indicated
      significant improvements in pain intensity and functional disability. Quality of
      life showed significant improvements in the physical functioning (P=.007), bodily
      pain (P=.018), general health (P=.022), vitality (P=.046), and physical component
      scores (P=.002) of the SF-36. The FABQ, cervical ROM, and mental component score
      of the SF-36 showed no significant improvements. CONCLUSIONS: The smartphone
      based exercise program with an embedded self-classification algorithm improves
      the pain intensity and perceived physical health of office workers with neck
      pain, although not enough to affect their mental and emotional states.

PMID- 27693423
TI  - Possible influence of vitamin D on male reproduction.
AB  - Vitamin D is a versatile signaling molecule with an established role in the
      regulation of calcium homeostasis and bone health. In recent years the spectrum
      of vitamin D target organs has expanded and a reproductive role is supported by
      the presence of the vitamin D receptor (VDR) and the vitamin D metabolizing
      enzymes in the gonads, reproductive tract, and human spermatozoa. Interestingly,
      expression levels of VDR and the vitamin D inactivating enzyme CYP24A1 in human
      spermatozoa serve as positive predictive markers of semen quality and are higher
      expressed in spermatozoa from normal than infertile men. VDR mediates a non
      genomic increase in intracellular calcium concentration, sperm motility, and
      induces the acrosome reaction. Furthermore, functional animal model studies have
      shown that vitamin D is important for sex steroid production, estrogen signaling,
      and semen quality. Cross-sectional clinical studies have supported the notion of
      a positive association between serum 25-hydroxyvitamin D (25-OHD) level and semen
      quality in both fertile and infertile men. However, it remains to be determined
      whether this association reflects a causal effect. The VDR is ubiquitously
      expressed and activated vitamin D is a regulator of insulin, aromatase, and
      osteocalcin. Hence, it is plausible that the influence of vitamin D on gonadal
      function may be mediated indirectly through other vitamin D regulated endocrine
      factors. Recent studies have indicated that vitamin D supplementation may be
      beneficial for couples in need of assisted reproductive techniques as high serum
      vitamin D levels were found to be associated with a higher chance of achieving
      pregnancy. Randomized clinical trials are needed to determine whether systemic
      changes in vitamin D metabolites can influence semen quality, fertility, and sex
      steroid production in infertile men. In this review known and possible future
      implications of vitamin D in human male reproduction function will be discussed.

PMID- 27693422
TI  - Endogenously produced nonclassical vitamin D hydroxy-metabolites act as "biased"
      agonists on VDR and inverse agonists on RORalpha and RORgamma.
AB  - The classical pathway of vitamin D activation follows the sequence D3->25(OH)D3
      >1,25(OH)2D3 with the final product acting on the receptor for vitamin D (VDR).
      An alternative pathway can be started by the action of CYP11A1 on the side chain
      of D3, primarily producing 20(OH)D3, 22(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3 and
      17,20,23(OH)3D3. Some of these metabolites are hydroxylated by CYP27B1 at
      C1alpha, by CYP24A1 at C24 and C25, and by CYP27A1 at C25 and C26. The products
      of these pathways are biologically active. In the epidermis and/or serum or
      adrenals we detected 20(OH)D3, 22(OH)D3, 20,22(OH)2D3, 20,23(OH)2D3,
      17,20,23(OH)3D3, 1,20(OH)2D3, 1,20,23(OH)3D3, 1,20,22(OH)3D3, 20,24(OH)2D3,
      1,20,24(OH)3D3, 20,25(OH)2D3, 1,20,25(OH)3D3, 20,26(OH)2D3 and 1,20,26(OH)3D3.
      20(OH)D3 and 20,23(OH)2D3 are non-calcemic, while the addition of an OH at
      C1alpha confers some calcemic activity. Molecular modeling and functional assays
      show that the major products of the pathway can act as "biased" agonists for the
      VDR with high docking scores to the ligand binding domain (LBD), but lower than
      that of 1,25(OH)2D3. Importantly, cell based functional receptor studies and
      molecular modeling have identified the novel secosteroids as inverse agonists of
      both RORalpha and RORgamma receptors. Specifically, they have high docking scores
      using crystal structures of RORalpha and RORgamma LBDs. Furthermore, 20(OH)D3 and
      20,23(OH)2D3 have been tested in a cell model that expresses a Tet-on RORalpha or
      RORgamma vector and a RORE-LUC reporter (ROR-responsive element), and in a
      mammalian 2-hybrid model that test interactions between an LBD-interacting LXXLL
      peptide and the LBD of RORalpha/gamma. These assays demonstrated that the novel
      secosteroids have ROR-antagonist activities that were further confirmed by the
      inhibition of IL17 promoter activity in cells overexpressing RORalpha/gamma. In
      conclusion, endogenously produced novel D3 hydroxy-derivatives can act both as
      "biased" agonists of the VDR and/or inverse agonists of RORalpha/gamma. We
      suggest that the identification of large number of endogenously produced
      alternative hydroxy-metabolites of D3 that are biologically active, and of
      possible alternative receptors, may offer an explanation for the pleiotropic and
      diverse activities of vitamin D, previously assigned solely to 1,25(OH)2D3 and
      VDR.

PMID- 27693424
TI  - Differentiation of Human Embryonic Stem Cells to Endothelial Progenitor Cells on
      Laminins in Defined and Xeno-free Systems.
AB  - A major hurdle for in vitro culturing of primary endothelial cells (ECs) is that
      they readily dedifferentiate, hampering their use for therapeutic applications.
      Human embryonic stem cells (hESCs) may provide an unlimited cell source; however,
      most current protocols deriving endothelial progenitor cells (EPCs) from hESCs
      use direct differentiation approaches albeit on undefined matrices, yet final
      yields are insufficient. We developed a method to culture monolayer hESCs on stem
      cell niche laminin (LN) LN511 or LN521 matrix. Here, we report a chemically
      defined, xeno-free protocol for differentiation of hESCs to EPCs using LN521 as
      the main culture substrate. We were able to generate ~95% functional EPCs defined
      as VEGFR2+CD34+CD31+VE-Cadherin+. RNA-sequencing analyses of hESCs, EPCs, and
      primary human umbilical vein endothelial cells showed differentiation-related EC
      expression signatures, regarding basement membrane composition, cell-matrix
      interactions, and changes in endothelial lineage markers. Our results may
      facilitate production of stable ECs for the treatment of vascular diseases and in
      vitro cell modeling.

PMID- 27693425
TI  - Amyloid beta Is Not the Major Factor Accounting for Impaired Adult Hippocampal
      Neurogenesis in Mice Overexpressing Amyloid Precursor Protein.
AB  - Adult hippocampal neurogenesis was impaired in several Alzheimer's disease models
      overexpressing mutant human amyloid precursor protein (hAPP). However, the
      effects of wild-type hAPP on adult neurogenesis and whether the impaired adult
      hippocampal neurogenesis was caused by amyloid beta (Abeta) or APP remained
      unclear. Here, we found that neurogenesis was impaired in the dentate gyrus (DG)
      of adult mice overexpressing wild-type hAPP (hAPP-I5) compared with controls.
      However, the adult hippocampal neurogenesis was more severely impaired in hAPP-I5
      than that in hAPP-J20 mice, which express similar levels of hAPP mRNA but much
      higher levels of Abeta. Furthermore, reducing Abeta levels did not affect the
      number of doublecortin-positive cells in the DG of hAPP-J20 mice. Our results
      suggested that hAPP was more likely an important factor inhibiting adult
      neurogenesis, and Abeta was not the major factor affecting neurogenesis in the
      adult hippocampus of hAPP mice.

PMID- 27693426
TI  - Restoration of Corneal Transparency by Mesenchymal Stem Cells.
AB  - Transparency of the cornea is indispensable for optimal vision. Ocular trauma is
      a leading cause of corneal opacity, leading to 25 million cases of blindness
      annually. Recently, mesenchymal stem cells (MSCs) have gained prominence due to
      their inflammation-suppressing and tissue repair functions. Here, we investigate
      the potential of MSCs to restore corneal transparency following ocular injury.
      Using an in vivo mouse model of ocular injury, we report that MSCs have the
      capacity to restore corneal transparency by secreting high levels of hepatocyte
      growth factor (HGF). Interestingly, our data also show that HGF alone can restore
      corneal transparency, an observation that has translational implications for the
      development of HGF-based therapy.

PMID- 27693428
TI  - Anticancer drug-loaded hydrogels as drug delivery systems for the local treatment
      of glioblastoma.
AB  - Among central nervous system tumors, Glioblastoma (GBM) is the most common,
      aggressive and neurological destructive primary brain tumor in adults. Standard
      care therapy for GBM consists in surgical resection of the accessible tumor
      (without causing neurological damage) followed by chemoradiation. However,
      several obstacles limit the assessment of tumor response and the delivery of
      cytotoxic agents at the tumor site, leading to a lack of effectiveness of
      conventional treatments against GBM and fatal outcome. Despite the efforts of the
      scientific community to increase the long-term benefits of GBM therapy, at the
      moment GBM remains incurable. Among the strategies that have been adopted in the
      last two decades to find new and efficacious therapies for the treatment of GBM,
      the local delivery of chemotherapeutic drugs in the tumor resection cavity
      emerged. In this review, our aim is to provide an overview on hydrogels loaded
      with anticancer drugs for the treatment of GBM recently used in preclinical and
      clinical studies, their advantages and major limitations for clinical
      translation. This review is divided in three parts: the first one describes the
      context of GBM and its current treatments, with a highlight on the role of local
      delivery in GBM treatment and the development of GBM resection murine models.
      Then, recent developments in the use of anticancer drug-loaded hydrogels for the
      treatment of GBM will be detailed. The final section will be focused on the
      limitations for in vivo studies, clinical translation and the clinical
      perspectives to the development of hydrogels.

PMID- 27693427
TI  - ESC-Derived BDNF-Overexpressing Neural Progenitors Differentially Promote
      Recovery in Huntington's Disease Models by Enhanced Striatal Differentiation.
AB  - Huntington's disease (HD) is characterized by fatal motoric failures induced by
      loss of striatal medium spiny neurons. Neuronal cell death has been linked to
      impaired expression and axonal transport of the neurotrophin BDNF (brain-derived
      neurotrophic factor). By transplanting embryonic stem cell-derived neural
      progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as
      a potential HD therapy approach. Transplantation of purified neural progenitors
      was analyzed in a quinolinic acid (QA) chemical and two genetic HD mouse models
      (R6/2 and N171-82Q) on the basis of distinct behavioral parameters, including
      CatWalk gait analysis. Explicit rescue of motor function by BDNF neural
      progenitors was found in QA-lesioned mice, whereas genetic mouse models displayed
      only minor improvements. Tumor formation was absent, and regeneration was
      attributed to enhanced neuronal and striatal differentiation. In addition, adult
      neurogenesis was preserved in a BDNF-dependent manner. Our findings provide
      significant insight for establishing therapeutic strategies for HD to ameliorate
      neurodegenerative symptoms.

PMID- 27693429
TI  - Fibromodulin: A regulatory molecule maintaining cellular architecture for normal
      cellular function.
AB  - Fibromodulin (FMOD) is a small leucine-rich proteoglycan that plays roles in a
      series of biological and pathophysiological processes. The interaction between
      FMOD and lysyl oxidase (LOX; collagen cross-linking enzyme) helps regulate
      extracellular matrix composition, and thereby, provides a permissive environment
      for regulating cellular turnover. FMOD has been mostly studied in the context of
      matrix component assembly, but during recent years its association with muscle
      development, cell reprogramming, and the angiogenic program have demonstrated its
      activities well beyond extracellular matrix maintenance. In fact, the involvement
      of FMOD in these cellular processes places it the centrum of cellular behaviour
      and ultimately of tissue properties. Thus, a clear view of the impact FMOD has on
      tissue integrity would aid its exploitation for tissue modelling and in the
      treatment of different disorders.

PMID- 27693430
TI  - miR-483 is a self-regulating microRNA and can activate its own expression via
      USF1 in HeLa cells.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that constitute a fundamental part
      of post-transcriptional gene regulation in mammalian cells. We have recently
      identified the intronic miR-483, which functions as an important regulator of
      protein synthesis during mild hypothermia in human and rodent cells. Since only
      very little is known about transcriptional regulation of intronic miRNAs and
      their host genes, we thoroughly investigated the regulation of miR-483 expression
      and its host gene IGF2 in HeLa cells. We demonstrate that miR-483 is regulated
      and expressed independently of its host gene IGF2 during mild hypothermia.
      Strikingly, we also discovered that miR-483 enhances its own transcription by up
      regulation of the transcription factor USF1, which activates a promoter element
      upstream of the MIR483 gene. However, since the USF1 mRNA lacks binding sites for
      miR-483-5p and -3p, USF1 expression is likely enhanced in an indirect manner. Our
      results suggest that miR-483 may self-regulate its own expression independently
      of its host gene IGF2 in human HeLa cells. This points towards a novel feed
      forward mechanism, in which selected intronic miRNAs may activate their own
      expression by transcriptional activation of upstream regulators.

PMID- 27693431
TI  - Chasing the personalized medicine dream through biomarker validation in
      colorectal cancer.
AB  - Colorectal cancer (CRC) is a major health burden worldwide. The optimal approach
      to the diagnosis, management, and treatment of CRC involves multidisciplinary and
      integrated management practices. The field is rapidly changing because of recent
      advancements in delineating the molecular basis of tumorigenesis, introduction of
      targeted therapy, varied patient response to mainstay chemotherapeutics,
      biological drugs, and the effective combination regimes being used for treatment.
      Recent meta-analysis studies, which tend to establish few clinically useful
      predictor biomarkers, identify inconsistent results and limitations of the
      trials. Therefore, molecular pathological epidemiology discipline initiatives are
      promising. Here, we provide an overview of the potential of biomarker validation
      for personalized medicine by focusing largely on metastatic (m)CRC. We also
      highlight new candidate predictive and prognostic biomarkers.

PMID- 27693432
TI  - Pharmaceutical and biomaterial engineering via electrohydrodynamic atomization
      technologies.
AB  - Complex micro- and nano-structures enable crucial developments in the healthcare
      remit (e.g., pharmaceutical and biomaterial sciences). In recent times, several
      technologies have been developed and explored to address key healthcare
      challenges (e.g., advanced chemotherapy, biomedical diagnostics and tissue
      regeneration). Electrohydrodynamic atomization (EHDA) technologies are rapidly
      emerging as promising candidates to address these issues. The fundamental
      principle driving EHDA engineering relates to the action of an electric force
      (field) on flowing conducting medium (formulation) giving rise to a stable Taylor
      cone. Through careful optimization of process parameters, material properties and
      selection, nozzle and needle design, and collection substrate method, complex
      active micro- and nano-structures are engineered. This short review focuses on
      key selected recent and established advances in the field of pharmaceutical and
      biomaterial applications.

PMID- 27693433
TI  - Follicular lymphoma (FL): Immunological tolerance theory in FL.
AB  - The ultimate cause of follicular lymphoma (FL) remains unknown. Remarkably,
      almost nothing is known about immunological tolerance mechanisms that might
      contribute to FL development. Immunological tolerance mechanisms, like other
      stimuli, also induce persistent changes of B cell receptors that induce genetic
      instability and molecular aberrations promoting the development of a neoplasm.
      Using the same method as Burnet, we provide a new perspective taking advantage of
      the comparison of a normal linear B cell differentiation process and FL
      development within the framework of clonal selection theory. We propose that FL
      is a malignancy of cells that acquire both translocation t(14;18) and self-BCR,
      inducing them to proliferate and mature, resistant to negative selection.
      Additional genetic damage induced by non-apoptotic tolerance mechanisms, such as
      receptor editing, may transform a self-reactive B cell with t(14;18) into an FL.
      The result of tolerogenic mechanisms and genetic aberrations is the survival of
      FL B cell clones with similar markers and homogenous gene expression signatures
      despite the different stages of maturation at which the molecular damage occurs.
      To antagonize further growth advantage due to self-antigen recognition and
      chronic activation of tolerance mechanisms in the apoptosis-resistant background
      of FL B cells, inhibitors of BCR signaling may be promising therapeutic options.

PMID- 27693435
TI  - The different oscillation patterns of alpha band in the early and later stages of
      working memory maintenance.
AB  - A putative functional role for alpha oscillations in working memory remains
      controversial. However, recent evidence suggests that such oscillation may
      reflect distinct phases of working memory processing. The present study
      investigated alpha band (8-13Hz) activity during the maintenance stage of working
      memory using a modified Sternberg working memory task. Our results reveal that
      alpha power was concentrated primarily in the occipital cortex and was decreased
      during the early stage of maintenance (0-600ms), and subsequently increased
      during the later stage of maintenance (1000-1600ms). We suggest that reduced
      alpha power may be involved in focused attention during the working memory
      maintenance, whereas increased alpha power may reflect suppression of visual
      stimuli to facilitate internal processing related to the task. This
      interpretation is generally consistent with recent reports suggesting that
      variations in alpha power are associated with the representation and processing
      of information in the discrete time intervals during the working memory
      maintenance.

PMID- 27693434
TI  - Distinct regulation of atonal in a visual organ of Drosophila: Organ-specific
      enhancer and lack of autoregulation in the larval eye.
AB  - Drosophila has three types of visual organs, the larval eyes or Bolwig's organs
      (BO), the ocelli (OC) and the compound eyes (CE). In all, the bHLH protein Atonal
      (Ato) functions as the proneural factor for photoreceptors and effects the
      transition from progenitor cells to differentiating neurons. In this work, we
      investigate the regulation of ato expression in the BO primordium (BOP).
      Surprisingly, we find that ato transcription in the BOP is entirely independent
      of the shared regulatory DNA for the developing CE and OC. The core enhancer for
      BOP expression, atoBO, lies ~6kb upstream of the ato gene, in contrast to the
      downstream location of CE and OC regulatory elements. Moreover, maintenance of
      ato expression in the neuronal precursors through autoregulation-a common and
      ancient feature of ato expression that is well-documented in eyes, ocelli and
      chordotonal organs-does not occur in the BO. We also show that the atoBO enhancer
      contains two binding sites for the transcription factor Sine oculis (So), a core
      component of the progenitor specification network in all three visual organs.
      These binding sites function in vivo and are specifically bound by So in vitro.
      Taken together, our findings reveal that the control of ato transcription in the
      evolutionarily derived BO has diverged considerably from ato regulation in the
      more ancestral compound eyes and ocelli, to the extent of acquiring what appears
      to be a distinct and evolutionarily novel cis-regulatory module.

PMID- 27693436
TI  - The effect of varenicline on binge-like ethanol consumption in mice is beta4
      nicotinic acetylcholine receptor-independent.
AB  - BACKGROUND: Our laboratory has previously shown that the smoking-cessation agent
      varenicline, an agonist/partial agonist of alpha4beta2*, alpha3beta4*,
      alpha3beta2*, alpha6beta2* (* indicates the possibility of additional subunits)
      and alpha7 subunits of nicotinic acetylcholine receptors (nAChRs), reduces
      ethanol consumption in rats only after long-term exposure (12 weeks). As
      compounds having partial agonistic activity on alpha3beta4* nAChRs were shown to
      decrease ethanol consumption in rodents, we assessed here the involvement of the
      beta4 subunit in the effect of varenicline in the reduction of short- and long
      term binge-like ethanol drinking in mice. METHODS: We used the well-validated
      drinking-in-the-dark (DID) paradigm to model chronic binge-like ethanol drinking
      in beta4-/- and beta4+/+ littermate mice and compare the effect of
      intraperitoneal injection of varenicline (2mg/kg) on ethanol intake following
      short- (4 weeks) or long-term (12 weeks) exposure. RESULTS: Drinking pattern and
      amounts of ethanol intake were similar in beta4-/- and beta4+/+ mice.
      Interestingly, our results showed that varenicline reduces ethanol consumption
      following short- and long-term ethanol exposure in the DID. Although the effect
      of varenicline on the reduction of ethanol consumption was slightly more
      pronounced in beta4-/- mice than their beta4+/+ littermates no significant
      differences were observed between genotypes. CONCLUSION: In mice, varenicline
      reduces binge-like ethanol consumption both after short- and long-term exposure
      in the DID and this effect is independent of beta4 nAChR subunit.

PMID- 27693437
TI  - Parkinson's disease classification using gait analysis via deterministic
      learning.
AB  - Gait analysis plays an important role in maintaining the well-being of human
      mobility and health care, and is a valuable tool for obtaining quantitative
      information on motor deficits in Parkinson's disease (PD). In this paper, we
      propose a method to classify (diagnose) patients with PD and healthy control
      subjects using gait analysis via deterministic learning theory. The
      classification approach consists of two phases: a training phase and a
      classification phase. In the training phase, gait characteristics represented by
      the gait dynamics are derived from the vertical ground reaction forces under the
      usual and self-selected paces of the subjects. The gait dynamics underlying gait
      patterns of healthy controls and PD patients are locally accurately approximated
      by radial basis function (RBF) neural networks. The obtained knowledge of
      approximated gait dynamics is stored in constant RBF networks. The gait patterns
      of healthy controls and PD patients constitute a training set. In the
      classification phase, a bank of dynamical estimators is constructed for all the
      training gait patterns. Prior knowledge of gait dynamics represented by the
      constant RBF networks is embedded in the estimators. By comparing the set of
      estimators with a test gait pattern of a certain PD patient to be classified
      (diagnosed), a set of classification errors are generated. The average L1 norms
      of the errors are taken as the classification measure between the dynamics of the
      training gait patterns and the dynamics of the test PD gait pattern according to
      the smallest error principle. When the gait patterns of 93 PD patients and 73
      healthy controls are classified with five-fold cross-validation method, the
      accuracy, sensitivity and specificity of the results are 96.39%, 96.77% and
      95.89%, respectively. Based on the results, it may be claimed that the features
      and the classifiers used in the present study could effectively separate the gait
      patterns between the groups of PD patients and healthy controls.

PMID- 27693438
TI  - Efficacy of chlorhexidine application to umbilical cord on neonatal mortality in
      Pemba, Tanzania: a community-based randomised controlled trial.
AB  - BACKGROUND: In low-income countries, including the east African region, a third
      of neonatal deaths are due to infections. A substantial proportion of these have
      been attributed to sepsis, which can result from umbilical cord infections.
      Evidence from Asia suggests that chlorhexidine application to the neonatal
      umbilical cord reduces mortality, but no data from Africa are available. We aimed
      to assess the effect of umbilical cord cleansing with 4% chlorhexidine solution
      on neonatal mortality and omphalitis in rural settings of sub-Saharan Africa.
      METHODS: We did a community-based randomised controlled trial on Pemba Island,
      Zanzibar, Tanzania. All eligible babies (aged 1 h to 48 h, without congenital
      malformations) from hospital-based and community-based deliveries on Pemba Island
      were enrolled. Participants were randomly assigned to either 4% free
      chlorhexidine for cord care or to dry cord care using a computer-generated random
      sequence. For babies allocated to the chlorhexidine group, mothers or caretakers
      were advised to apply the solution to the cord every day until 3 days after the
      cord had dropped off. Cord stumps were examined for redness, pus, swelling, and
      foul odour on day 0, 1, 4, 10, and 28. The primary outcome for this study was
      mortality until day 28 on an intention-to-treat basis. The trial is registered
      with ClinicalTrials.gov, number NCT01528852. FINDINGS: Between May 19, 2011, and
      Aug 31, 2014, 36 911 newborn babies were enrolled into the chlorhexidine (n=18
      015) and dry cord care study (n=18 896) groups. 17 468 (96.9%) of 18 015 neonates
      in the chlorhexidine group were available for complete follow-up (28 days)
      compared with 18 384 (97.3%) of 18 896 neonates in the dry cord care group.
      Mortality rate in the chlorhexidine group (10.5 deaths per 1000 livebirths) was
      not significantly lower than that in the dry cord care group (11.7 per 1000
      livebirths; relative risk 0.90, 0.74-1.09; p=0.27). INTERPRETATION: Our findings
      do not support the use of chlorhexidine for reduction of neonatal mortality in
      this east African setting, which might not justify a change in the WHO policy. To
      inform global policy, a detailed meta-analysis and pooled analysis needs to be
      undertaken using data from both African and Asian settings. FUNDING: Bill &
      Melinda Gates Foundation.

PMID- 27693440
TI  - No reason to change WHO guidelines on cleansing the umbilical cord.

PMID- 27693439
TI  - Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in
      Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial.
AB  - BACKGROUND: Chlorhexidine umbilical cord washes reduce neonatal mortality in
      south Asian populations with high neonatal mortality rates and predominantly home
      based deliveries. No data exist for sub-Saharan African populations with lower
      neonatal mortality rates or mostly facility-based deliveries. We compared the
      effect of chlorhexidine with dry cord care on neonatal mortality rates in Zambia.
      METHODS: We undertook a cluster-randomised controlled trial in Southern Province,
      Zambia, with 90 health facility-based clusters. We enrolled women who were in
      their second or third trimester of pregnancy, aged at least 15 years, and who
      would remain in the catchment area for follow-up of 28 days post-partum. Newborn
      babies received clean dry cord care (control) or topical application of 10 mL of
      a 4% chlorhexidine solution once per day until 3 days after cord drop
      (intervention), according to cluster assignment. We used stratified, restricted
      randomisation to divide clusters into urban or two rural groups (located <40 km
      or >=40 km to referral facility), and randomly assigned clusters (1:1) to use
      intervention (n=45) or control treatment (n=45). Sites, participants, and field
      monitors were aware of their study assignment. The primary outcomes were all
      cause neonatal mortality within 28 days post-partum and all-cause neonatal
      mortality within 28 days post-partum among babies who survived the first 24 h of
      life. Analysis was by intention to treat. Neonatal mortality rate was compared
      with generalised estimating equations. This study is registered at
      ClinicalTrials.gov (NCT01241318). FINDINGS: From Feb 15, 2011, to Jan 30, 2013,
      we screened 42 356 pregnant women and enrolled 39 679 women (mean 436.2 per
      cluster [SD 65.3]), who had 37 856 livebirths and 723 stillbirths; 63.8% of
      deliveries were facility-based. Of livebirths, 18 450 (99.7%) newborn babies in
      the chlorhexidine group and 19 308 (99.8%) newborn babies in the dry cord care
      group were followed up to day 28 or death. 16 660 (90.0%) infants in the
      chlorhexidine group had chlorhexidine applied within 24 h of birth. We found no
      significant difference in neonatal mortality rate between the chlorhexidine group
      (15.2 deaths per 1000 livebirths) and the dry cord care group (13.6 deaths per
      1000 livebirths; risk ratio [RR] 1.12, 95% CI 0.88-1.44). Eliminating day 0
      deaths yielded similar findings (RR 1.12, 95% CI 0.86-1.47). INTERPRETATION:
      Despite substantial reductions previously reported in south Asia, chlorhexidine
      cord applications did not significantly reduce neonatal mortality rates in
      Zambia. Chlorhexidine cord applications do not seem to provide clear benefits for
      newborn babies in settings with predominantly facility-based deliveries and lower
      (<30 deaths per 1000 livebirths) neonatal mortality rates. FUNDING: Bill &
      Melinda Gates Foundation.

PMID- 27693441
TI  - Interventions for age-related diseases: Shifting the paradigm.
AB  - Over 60% of people aged over 65 are affected by multiple morbidities, which are
      more difficult to treat, generate increased healthcare costs and lead to poor
      quality of life compared to individual diseases. With the number of older people
      steadily increasing this presents a societal challenge. Age is the major risk
      factor for age-related diseases and recent research developments have led to the
      proposal that pharmacological interventions targeting common mechanisms of ageing
      may be able to delay the onset of multimorbidity. Here we review the state of the
      knowledge of multimorbidity, appraise the available evidence supporting the role
      of mechanisms of ageing in the development of the most common age-related
      diseases and assess potential molecules that may successfully target those key
      mechanisms.

PMID- 27693443
TI  - The effects of lower-body compression garments on walking performance and
      perceived exertion in adults with CVD risk factors.
AB  - OBJECTIVES: Compression garments are used by athletes in attempts to enhance
      performance and recovery, although evidence to support their use is equivocal.
      Reducing the exertion experienced during exercise may encourage sedentary
      individuals to increase physical activity. The aim of this study was to assess
      the effect of compression garments on walking performance (self-paced and
      enforced pace) and rate of perceived exertion (RPE) in adults who presented with
      two or more CVD risk factors. Participants (n=15, 10 female, 58.9+/-11.5 years,
      BMI 27.5+/-4.5kgm2) were recruited. DESIGN: A repeated measures design. METHODS:
      Participants were randomised to Modified Bruce Protocol (enforced pace), or the
      6min walk test (self-paced), and completed the test wearing compression garments
      or normal exercise clothes (Control). Outcome measures included stage completed,
      gross efficiency (%) and RPE in Modified Bruce Protocol, and distance walked (m)
      and RPE in 6 min walk test. RESULTS: In the Modified Bruce Protcol participants
      had a higher RPE (15.5+/-2.5 vs 14.3+/-2.2) and a lower efficiency (19.1+/-5.9 vs
      21.1+/-6.7) in the compression garment condition compared with control, p<0.05.
      In the 6 min walk test participants walked 9% less in the compression garment
      condition (p<0.05) but did not have a lower RPE. CONCLUSIONS: Compared with
      previous studies reporting enhanced or no effects of compression garments on
      performance or RPE, this study shows adverse effects of such clothing in
      untrained individuals with CVD risk factors. The mechanisms underlying this
      negative effect require further exploration. Use of garments designed for the
      athletic individuals may not be suitable for the wider population.

PMID- 27693442
TI  - Hip abductor strength and lower extremity running related injury in distance
      runners: A systematic review.
AB  - OBJECTIVES: Determine the association between hip abduction strength and lower
      extremity running related injury in distance runners. DESIGN: Systematic review.
      METHODS: Prospective longitudinal and cross sectional studies that quantified hip
      abduction strength and provided diagnosis of running related injury in distance
      runners were included and assessed for quality. Effect size was calculated for
      between group differences in hip abduction strength. RESULTS: Of the 1841
      articles returned in the initial search, 11 studies matched all inclusion
      criteria. Studies were grouped according to injury: iliotibial band syndrome,
      patellofemoral pain syndrome, medial tibial stress syndrome, tibial stress
      fracture, and Achilles tendinopathy, and examined for strength differences
      between injured and non-injured groups. Meaningful differences were found in the
      studies examining iliotibial band syndrome. Three of five iliotibial band
      syndrome articles found weakness in runners with iliotibial band syndrome; two
      were of strong methodological rigor and both of those found a relationship
      between weakness and injury. Other results did not form associative or predictive
      relationships between weakness and injury in distance runners. CONCLUSIONS: Hip
      abduction weakness evaluated by hand held dynamometer may be associated with
      iliotibial band syndrome in distance runners as suggested by several cross
      sectional studies but is unclear as a significant factor for the development of
      patellofemoral pain syndrome, medial tibial stress syndrome, tibial stress
      fracture or Achilles tendinopathy according to the current literature. Future
      studies are needed with consistent methodology and inclusion of all distance
      running populations to determine the significance of hip abduction strength in
      relationship to lower extremity injury.

PMID- 27693444
TI  - Appearance of Far Peripheral Retina in Normal Eyes by Ultra-widefield Fluorescein
      Angiography.
AB  - PURPOSE: To characterize the appearance of the far peripheral retina of normal
      eyes using ultra-widefield fluorescein angiography (UWFA). DESIGN: Cross
      sectional study. METHODS: This study enrolled 101 eyes with best-corrected visual
      acuity >=20/20, with refractive error <3.00 diopters, and without visible retinal
      pathologic changes under a slit lamp-based condensing lens. The far peripheral
      retina was detected by UWFA. Ciliary body thickness (CBT) at 3 mm (CBT1) and 2 mm
      (CBT2) posterior to the scleral spur was measured by ultrasound biomicroscopy.
      RESULTS: In the far peripheral retina, granular background fluorescence (GB)
      appeared in all eyes (100%), a mottled fluorescent band (MB) appeared in 44 eyes
      (43.6%), and retinal vascular leakage (VL) appeared in 20 eyes (19.8%). According
      to peripheral angiographic findings, the eyes were allocated into 3 groups: Group
      1 (MB- and VL-), Group 2 (MB+ and VL-), and Group 3 (MB-/+ and VL+). Ultrasound
      biomicroscopy showed ciliary body edema and exudates in Group 3. The mean CBT1
      (mm) and CBT2 (mm) of Group 3 were greater than those of Group 1 and Group 2
      (0.315 +/- 0.037 vs 0.240 +/- 0.019 vs 0.251 +/- 0.030; 0.571 +/- 0.084 vs 0.375
      +/- 0.051 vs 0.410 +/- 0.050, P < .001 for both CBT1 and CBT2). The mean CBT1 and
      CBT2 showed no difference between Group 1 and Group 2 (P = .575 for CBT1; P =
      .150 for CBT2). CONCLUSIONS: Normal peripheral retinas generally show granular
      background fluorescence, with or without a mottled fluorescent band.

PMID- 27693445
TI  - Reversal of cardiac vagal effects of physostigmine by adjunctive muscarinic
      blockade.
AB  - Pre-treatment with reversible acetylcholinesterase (AChE) inhibitors is an
      effective strategy for reducing lethality following organophosphate nerve agent
      exposure. AChE inhibition may have unwanted cardiac side effects, which could be
      negated by adjunctive anti-cholinergic therapy. The aims of the present study
      were to examine the concentration-dependent effects of physostigmine on cardiac
      responses to vagus nerve stimulation (VNS), to test whether adjunctive treatment
      with hyoscine can reverse these effects and to assess the functional interaction
      and electrophysiological consequences of a combined pre-treatment. Studies were
      performed in an isolated innervated rabbit heart preparation. The reduction in
      heart rate with VNS was augmented by physostigmine (1-1000nmol/L), in a
      concentration-dependent manner - with an EC50 of 19nmol/L. Hyoscine was shown to
      be effective at blocking the cardiac responses to VNS with an IC50 of 11nmol/L.
      With concomitant perfusion of physostigmine, the concentration-response curve for
      hyoscine was shifted downward and to the right, increasing the concentration of
      hyoscine required to normalise (to control values) the effects of physostigmine
      on heart rate. At the lowest concentration of hyoscine examined (1nmol/L) a
      modest potentiation of heart rate response to VNS (+15+/-3%) was observed. We
      found no evidence of cardiac dysfunction or severe electrophysiological
      abnormalities with either physostigmine or hyoscine alone, or as a combined drug
      therapy. The main finding of this study is that hyoscine, at concentrations
      greater than 10-8M, is effective at reversing the functional effects of
      physostigmine on the heart. However, low-concentrations of hyoscine may augment
      cardiac parasympathetic control.

PMID- 27693446
TI  - Propylparaben reduces the excitability of hippocampal neurons by blocking sodium
      channels.
AB  - Propylparaben (PPB) is an antimicrobial preservative widely used in food,
      cosmetics, and pharmaceutics. Virtual screening methodologies predicted
      anticonvulsant activity of PPB that was confirmed in vivo. Thus, we explored the
      effects of PPB on the excitability of hippocampal neurons by using standard patch
      clamp techniques. Bath perfusion of PPB reduced the fast-inactivating sodium
      current (INa) amplitude, causing a hyperpolarizing shift in the inactivation
      curve of the INa, and markedly delayed the sodium channel recovery from the
      inactivation state. Also, PPB effectively suppressed the riluzole-sensitive,
      persistent sodium current (INaP). PPB perfusion also modified the action
      potential kinetics, and higher concentrations of PPB suppressed the spike
      activity. Nevertheless, the modulatory effects of PPB did not occur when PPB was
      internally applied by whole-cell dialysis. These results indicate that PPB
      reduces the excitability of CA1 pyramidal neurons by modulating voltage-dependent
      sodium channels. The mechanistic basis of this effect is a marked delay in the
      recovery from inactivation state of the voltage-sensitive sodium channels. Our
      results indicate that similar to local anesthetics and anticonvulsant drugs that
      act on sodium channels, PPB acts in a use-dependent manner.

PMID- 27693447
TI  - A Randomized Study of Intraoperative Autologous Retropubic Urethral Sling on
      Urinary Control after Robotic Assisted Radical Prostatectomy.
AB  - PURPOSE: We evaluated whether placement of a retropubic urethral sling fashioned
      from autologous vas deferens during robotic assisted radical prostatectomy would
      improve recovery of continence. MATERIALS AND METHODS: In a phase 2, single blind
      trial age stratified patients were randomized to undergo robotic assisted radical
      prostatectomy by multiple surgeons with or without sling placement. The outcomes
      were complete continence (0 urinary pads of any type) and near continence (0, an
      occasional or 1 pad per day) at 6 months, which was assessed by the Fisher exact
      test and logistic regression. The Kaplan-Meier method and the log rank test were
      used to evaluate time to continence. EPIC-UIN (Expanded Prostate Cancer Index
      Composite-Urinary Inventory) and I-PSS (International Prostate Symptom Score) 1,
      3 and 6 months after catheter removal were evaluated by mixed models for repeated
      measures. RESULTS: Of 203 patients who were recruited 95 and 100 were randomized
      to undergo sling and no sling placement, respectively, and completed
      postoperative interviews. Six months after surgery the proportions reporting
      complete and near continence (66% and 87%, respectively) and times to complete
      and near continence were similar in the groups. Younger age was associated with a
      higher likelihood of complete continence (OR 1.74 per decreasing 5-year interval,
      95% CI 1.23-2.48, p <0.01) and near continence (OR 2.18 per decreasing 5-year
      interval, 95% CI 1.21-3.92, p <0.01) adjusting for clinical, urinary and surgical
      factors. Adjusted EPIC-UIN and I-PSS scores changed with time but did not differ
      between the groups. No serious adverse events were observed. CONCLUSIONS: This
      trial failed to demonstrate a benefit of autologous urethral sling placement at
      robotic assisted radical prostatectomy on early return of continence at 6 months.
      Continence was related to patient age in adjusted models.

PMID- 27693448
TI  - PTEN Loss in Gleason Score 3 + 4 = 7 Prostate Biopsies is Associated with
      Nonorgan Confined Disease at Radical Prostatectomy.
AB  - PURPOSE: Men with intermediate risk prostate cancer have widely variable
      outcomes. Some suggest that active surveillance or less invasive therapies
      (brachytherapy or focal therapy) may be appropriate for some men with Gleason
      score 3 + 4 = 7 disease. Molecular markers may help further distinguish prostate
      cancers with aggressive behavior. We tested whether loss of the PTEN (phosphatase
      and tensin homolog) tumor suppressor in 3 + 4 = 7 tumor biopsies is associated
      with adverse pathology at prostatectomy. MATERIALS AND METHODS: We queried
      prostate needle biopsies from 2000 to 2014 with a maximum Gleason score of 3 + 4
      = 7 followed by prostatectomy. A total of 260 cases had PTEN status evaluable by
      clinical grade immunohistochemistry. Biopsy PTEN status was correlated with
      preoperative and postoperative clinicopathological parameters. RESULTS: PTEN loss
      was detected in 27% of 3 + 4 = 7 biopsies. Loss of PTEN was less common in tumors
      of African American men compared to European American men (9% vs 31%, p = 0.002).
      At prostatectomy, tumors with PTEN loss were more likely to show nonorgan
      confined disease compared to those with PTEN intact (52% vs 27%, p <0.001). In
      logistic regression models including age, race, prostate specific antigen,
      clinical stage and biopsy tumor involvement, PTEN loss at biopsy remained
      significantly associated with an increased risk of nonorgan confined disease (HR
      2.46, 95% CI 1.34-4.49, p = 0.004). On ROC analysis, the AUC for models including
      prostate specific antigen and clinical stage was increased from 0.61 to 0.67 upon
      inclusion of PTEN status. CONCLUSIONS: PTEN loss in a Gleason score 3 + 4 = 7
      biopsy is independently associated with an increased risk of nonorgan confined
      disease at prostatectomy. It adds to the preoperative parameters commonly used to
      predict pathological stage.

PMID- 27693449
TI  - The Economic Implications of a Reusable Flexible Digital Ureteroscope: A Cost
      Benefit Analysis.
AB  - PURPOSE: Questions remain regarding the durability and longevity of flexible
      ureteroscopes. The objective of this study was to estimate the potential economic
      benefits of single use, flexible digital ureteroscopes compared to our recent
      experience with reusable flexible digital ureteroscopes using cost-benefit
      analysis. MATERIALS AND METHODS: Ureteroscopic procedures were prospectively
      recorded over the 12-month period of February 2014 to February 2015. All flexible
      ureteroscopies were performed using Flex XC digital ureteroscopes (Karl Storz
      Endoscopy-America, El Segundo, California). Cost assessment was based on the
      original purchasing cost and repair-exchange fees divided by the number of cases.
      An algorithm was created to include per case reprocessing costs and calculate the
      benefit-to-cost ratio. This cost was compared to potential costs of the
      LithoVueTM, a single use digital ureteroscope. RESULTS: In 160 cases a flexible
      reusable ureteroscope was used. There was damage to 11 ureteroscopes during this
      time with an average of 12.5 cases to failure. Excluding original purchasing
      costs, the cost analysis revealed an amortized cost of $848.10 per use. After 99
      ureteroscope cases the cost-benefit analysis favored reusable ureteroscopes
      compared to disposable ureteroscopes. CONCLUSIONS: Digital ureteroscopes are the
      latest trend in the evolution of endourology. It appears that a disposable
      ureteroscope may be cost beneficial at centers with a lower case volume per year.
      However, institutions with a high volume of cases may find reusable ureteroscopes
      cost beneficial.

PMID- 27693450
TI  - Properties of the 4-Kallikrein Panel Outside the Diagnostic Gray Zone: Meta
      Analysis of Patients with Positive Digital Rectal Examination or Prostate
      Specific Antigen 10 ng/ml and Above.
AB  - PURPOSE: The 4-kallikrein panel, commercially available as the 4KscoreTM, is a
      reflex test for prostate cancer early detection that has been extensively
      validated in multiple international cohorts. It has been suggested that use of
      such reflex tests be limited to those with prostate specific antigen less than 10
      ng/ml and negative digital rectal examination. We aimed to determine the value of
      the panel in men outside this "diagnostic gray zone." MATERIALS AND METHODS: We
      performed an individual patient data meta-analysis using data from prior studies
      on the 4-kallikrein panel. We calculated the properties of the panel for
      predicting high grade (Gleason 7+) cancer in a subgroup of men with either
      positive digital rectal examination or prostate specific antigen 10 to 25 ng/ml.
      RESULTS: A total 2,891 men from 8 cohorts were included. An important proportion
      of patients, including 32% in the United States validation study, had prostate
      specific antigen 10 to 25 ng/ml or a positive digital rectal examination. For men
      with prostate specific antigen 10 to 25 ng/ml the fixed-effects estimate for the
      discrimination of the kallikrein model was 0.84 vs 0.69 for the base model
      (difference 0.128, 95% CI 0.098-0.159). In the positive digital rectal
      examination group discrimination was 0.82 vs 0.72 (difference 0.092, 95% CI 0.069
      0.115). Decision analysis showed a clinical net benefit for use of the panel in
      this subgroup with a reduction in biopsy rates of about 20% and only a small
      number of high grade cancers missed, or fewer than 3% of those not biopsied.
      CONCLUSIONS: The use of the kallikrein panel in men with a positive digital
      rectal examination or prostate specific antigen 10 to 25 ng/ml is justified.

PMID- 27693451
TI  - Crosstalk between the vitamin D receptor (VDR) and miR-214 in regulating SuFu, a
      hedgehog pathway inhibitor in breast cancer cells.
AB  - The vitamin D receptor (VDR), and its ligand 1alpha,25-dihydroxyvitamin D3
      (1,25D3) prevent breast cancer development and progression, yet the molecular
      mechanisms governing this are unclear. MicroRNAs (miRNAs) on the other hand,
      promote or inhibit breast cancer growth. To understand how VDR regulates miRNAs,
      we compared miRNA expression of wild-type (WT) and VDR knockout (VDRKO) breast
      cancer cells by a Mouse Breast Cancer miRNA PCR array. Compared to VDR WT cells,
      expressions of miR-214, miR-199a-3p and miR-199a-5p of the miR-199a/miR-214
      cluster were 42, 15, and 10 fold higher in VDRKO cells respectively.
      Overexpression of VDR in breast cancer cells reduced the miR-199a/miR-214 cluster
      expression by 30%. VDR status also negatively correlated with Dnm3os expression,
      a non-coding RNA transcript of the dynamin-3 gene encoding the miR-199a/miR-214
      cluster, suggesting that VDR represses this cluster through Dnm3os. Conversely,
      overexpression of miR-214 in MCF-7 and T47D cells antagonized VDR mediated
      signaling. Furthermore, there was a positive correlation between VDR status and
      the expression of Suppressor of fused gene (SuFu), a hedgehog pathway inhibitor.
      miR-214 on the other hand suppressed SuFu protein expression. These findings
      suggest a crosstalk between VDR and miR-214 in regulating hedgehog signaling in
      breast cancer cells, providing new therapies for breast cancer.

PMID- 27693452
TI  - Relative expression of the p75 neurotrophin receptor, tyrosine receptor kinase A,
      and insulin receptor in SH-SY5Y neuroblastoma cells and hippocampi from
      Alzheimer's disease patients.
AB  - We have previously shown in SH-SY5Y human neuroblastoma cells that the
      expressions of basal (75 kDa) and high molecular weight (HMW; 85 kDa) isoforms of
      the p75 neurotrophic receptor (p75NTR) are stimulated by amyloid-beta peptide1-42
      oligomers (AbetaOs) via the insulin-like growth factor-1 receptor (IGF-1R). On
      the other hand, it is known that AbetaOs inhibit insulin receptor (IR) signaling.
      The purpose of the present study was to determine the involvement of IR signaling
      in the regulation of p75 neurotrophin receptor (p75NTR) protein isoform
      expression in cultured SH-SY5Y cells and in hippocampi from late-stage human
      Alzheimer's disease (AD) brains. Interestingly, insulin induced the expression of
      basal and HMW p75NTR isoforms in SH-SY5Y cells, suggesting the presence of cross
      talk between the IR and IGF-1R for the regulation of p75NTR expression. Reducing
      IR signaling with an IR kinase inhibitor (AG 1024) or IR-targeted siRNAs
      increased HMW p75NTR expression and reduced tyrosine receptor kinase-A (Trk-A)
      expression as well as postsynaptic density protein 95 (PSD95) expression in SH
      SY5Y cells. Both basal and HMW p75NTR isoforms were increased in the hippocampi
      of post-mortem late-stage human AD brains (relative to non-AD brains), and the
      protein expression of HMW p75NTR was negatively associated with Trk-A expression,
      PSD95 expression, and IR expression. Thus, increased p75NTR expression,
      specifically an increased p75NTR-to-Trk-A ratio, is likely to play a role in
      synaptic loss and neuronal cell death in late-stage AD. Collectively, these
      findings suggest that increased expression of the p75NTR due to IR signaling
      inhibition by AbetaOs might be involved in the pathology of AD.

PMID- 27693453
TI  - Development of a neuroprotective potential algorithm for medicinal plants.
AB  - Medicinal plants are promising candidates for Alzheimer's disease (AD) research
      but there is lack of systematic algorithms and procedures to guide their
      selection and evaluation. Herein, we developed a Neuroprotective Potential
      Algorithm (NPA) by evaluating twenty-three standardized and chemically
      characterized Ayurvedic medicinal plant extracts in a panel of bioassays
      targeting oxidative stress, carbonyl stress, protein glycation, amyloid beta
      (Abeta) fibrillation, acetylcholinesterase (AChE) inhibition, and
      neuroinflammation. The twenty-three herbal extracts were initially evaluated for:
      1) total polyphenol content (Folin-Ciocalteu assay), 2) free radical scavenging
      capacity (DPPH assay), 3) ferric reducing antioxidant power (FRAP assay), 4)
      reactive carbonyl species scavenging capacity (methylglyoxal trapping assay), 5)
      anti-glycative effects (BSA-fructose, and BSA-methylglyoxal assays) and, 6) anti
      Abeta fibrillation effects (thioflavin-T assay). Based on assigned index scores
      from the initial screening, twelve extracts with a cumulative NPA score >=40 were
      selected for further evaluation for their: 1) inhibitory effects on AChE
      activity, 2) in vitro anti-inflammatory effects on murine BV-2 microglial cells
      (Griess assay measuring levels of lipopolysaccharide-induced nitric oxide
      species), and 3) in vivo neuroprotective effects on Caenorhabditis elegans post
      induction of Abeta1-42 induced neurotoxicity and paralysis. Among these, four
      extracts had a cumulative NPA score >=60 including Phyllanthus emblica (amla;
      Indian gooseberry), Mucuna pruriens (velvet bean), Punica granatum (pomegranate)
      and Curcuma longa (turmeric; curcumin). These extracts also showed protective
      effects on H2O2 induced cytotoxicity in differentiated cholinergic human neuronal
      SH-SY5Y and murine BV-2 microglial cells and reduced tau protein levels in the SH
      SY5Y neuronal cells. While published animal data support the neuroprotective
      effects of several of these Ayurvedic medicinal plant extracts, some remain
      unexplored for their anti-AD potential. Therefore, the NPA may be utilized, in
      part, as a strategy to help guide the selection of promising medicinal plant
      candidates for future AD-based research using animal models.

PMID- 27693454
TI  - Decorin interacting network: A comprehensive analysis of decorin-binding partners
      and their versatile functions.
AB  - Decorin, a prototype small leucine-rich proteoglycan, regulates a vast array of
      cellular processes including collagen fibrillogenesis, wound repair, angiostasis,
      tumor growth, and autophagy. This functional versatility arises from a wide array
      of decorin/protein interactions also including interactions with its single
      glycosaminoglycan side chain. The decorin-binding partners encompass numerous
      categories ranging from extracellular matrix molecules to cell surface receptors
      to growth factors and enzymes. Despite the diversity of the decorin interacting
      network, two main roles emerge as prominent themes in decorin function:
      maintenance of cellular structure and outside-in signaling, culminating in anti
      tumorigenic effects. Here we present contemporary knowledge regarding the decorin
      interacting network and discuss in detail the biological relevance of these
      pleiotropic interactions, some of which could be targeted by therapeutic
      interventions.

PMID- 27693455
TI  - Targeting cancer cells through antibiotics-induced mitochondrial dysfunction
      requires autophagy inhibition.
AB  - A significant part of current research studies utilizes various cellular models
      which imply specific antibiotics-containing media as well as antibiotics used for
      clonal selection or promoter de/activation. With the great success of developing
      such tools, mitochondria, once originated from bacteria, can be effectively
      targeted by antibiotics. For that reason, some studies propose antibiotics
      targeting of mitochondria as part of anticancer therapy. Here, we have focused on
      the effects of various classes of antibiotics on mitochondria in cancer and non
      cancer cells and demonlow mitochondrial membrane potential, reduced ATP
      production, altered morphology and lowered respiration rate which altogether
      suggested mitochondrial dysfunction (MDF). This was in parallel with increased
      level of reactive oxygen species (ROS) and decreased activity of mitochondrial
      respiration complexes. However, both survival and repopulation capacity of cancer
      cells was not significantly affected by the antibiotics, perhaps due to a
      glycolytic shift or activated autophagy. In turn, simultaneous inhibition of
      autophagy and treatment with antibiotics largely reduced tumorigenic properties
      of cancer cells suggesting potential strategy for anticancer therapy.

PMID- 27693456
TI  - Targeting miRNAs associated with surface expression of death receptors to
      modulate TRAIL resistance in breast cancer.
AB  - Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is capable of
      inducing apoptosis upon engagement of its death receptors (DRs) 4 and 5. TRAIL
      therapy has garnered intense interest as one of the most promising agents for
      cancer therapy, for its selective induction of tumor-cell apoptosis while low
      toxicity to most normal cells. However, a variety of breast cancer cell lines
      could be resistant to TRAIL-induced apoptosis. Absence of DR4 and DR5 on the
      breast cancer cell surface has been proposed to be critically involved in
      resistance to TRAIL and its agonistic antibodies. Moreover, endocytosis and
      autophagy in breast cancer cells could induce TRAIL resistance through
      downregulation of surface DR4/5. MicroRNAs (miRNAs), as endogenously expressed
      small non-coding RNAs, function as regulators of gene expression and involve
      tremendous biological processes including drug resistance. In this review, we
      highlight recent advances in the functional role of miRNAs in endocytosis and
      autophagy pathways. This review aims to present that, through regulation of
      critical molecules involved in autophagy and endocytosis, miRNAs could lead to
      mislocalization of DR4/5 in breast cancer cells and therefore play an important
      role in TRAIL-mediated apoptosis and TRAIL resistance.

PMID- 27693458
TI  - 2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol inhibits MDM2 and induces
      apoptosis in breast cancer cells through a p53-independent pathway.
AB  - 2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ) is a novel synthesized
      combretastatin A-4 (CA-4) analog that can be classified as a microtubule
      inhibitor. Our previous study demonstrated that SQ induced G2/M phase arrest and
      promoted apoptosis progression in breast cancer cells. In the present study, we
      found that SQ dissociated the MDM2-p53 complex and directly induced MDM2
      degradation through the ubiquitin-dependent proteasome pathway in MCF-7 and MDA
      MB-231 cells. Further, p53 was activated by SQ through regulation of its
      transcription, translation, and post-translation modification. More specifically,
      we demonstrated that SQ induced caspase-dependent but p53-independent apoptosis,
      and this apoptosis is associated with the inhibition of MDM2. We also showed that
      SQ exhibited superior in vivo efficacy and low toxicity than CA-4. The
      immunofluorescence histochemistry study indicated that SQ also inhibited MDM2
      expression in vivo. In summary, we report for the first time that SQ shows
      excellent anti-breast cancer activity in vivo and in vitro and induces p53
      independent apoptosis, which is associated with MDM2 inhibition. Therefore, the
      novel compound SQ has potential for therapeutic treatment of both wild-type and
      mutant p53 breast cancer.

PMID- 27693457
TI  - Compromized DNA repair as a basis for identification of cancer radiotherapy
      patients with extreme radiosensitivity.
AB  - A small percentage of cancer radiotherapy patients develop abnormally severe side
      effects as a consequence of intrinsic radiosensitivity. We analysed the gamma
      H2AX response to ex-vivo irradiation of peripheral blood lymphocytes (PBL) and
      plucked eyebrow hair follicles from 16 patients who developed severe late
      radiation toxicity following radiotherapy, and 12 matched control patients.
      Longer retention of the gamma-H2AX signal and lower colocalization efficiency of
      repair factors in over-responding patients confirmed that DNA repair in these
      individuals was compromised. Five of the radiosensitive patients harboured LoF
      mutations in DNA repair genes. An extensive range of quantitative parameters of
      the gamma-H2AX response were studied with the objective to establish a predictor
      for radiosensitivity status. The most powerful predictor was the combination of
      the fraction of the unrepairable component of gamma-H2AX foci and repair rate in
      PBL, both derived from non-linear regression analysis of foci repair kinetics. We
      introduce a visual representation of radiosensitivity status that allocates a
      position for each patient on a two-dimensional "radiosensitivity map". This
      analytical approach provides the basis for larger prospective studies to further
      refine the algorithm, ultimately to triage capability.

PMID- 27693459
TI  - Breast cancer-secreted miR-939 downregulates VE-cadherin and destroys the barrier
      function of endothelial monolayers.
AB  - Exosomes-secreted microRNAs play an important role in metastatic spread. During
      this process breast cancer cells acquire the ability to transmigrate through
      blood vessels by inducing changes in the endothelial barrier. We focused on miR
      939 that is predicted to target VE-cadherin, a component of adherens junction
      involved in vessel permeability. By in silico analysis miR-939 was found highly
      expressed in the basal-like tumor subtypes and in our cohort of 63 triple
      negative breast cancers (TNBCs) its expression significantly interacted with
      lymph node status in predicting disease-free survival probability. We
      demonstrated, in vitro, that miR-939 directly targets VE-cadherin leading to an
      increase in HUVECs monolayer permeability. MDA-MB-231 cells transfected with a
      miR-939 mimic, released miR-939 in exosomes that, once internalized in
      endothelial cells, favored trans-endothelial migration of MDA-MB-231-GFP cells by
      the disruption of the endothelial barrier. Notably, when up taken in endothelial
      cells exosomes caused VE-cadherin down-regulation specifically through miR-939 as
      we demonstrated by inhibiting miR-939 expression in exosomes-releasing TNBC
      cells. Together, our data indentify an extracellular pro-tumorigenic role for
      tumor-derived, exosome-associated miR-939 that can explain its association with
      worse prognosis in TNBCs.

PMID- 27693460
TI  - Vascular mimicry formation is promoted by paracrine TGF-beta and SDF1 of cancer
      associated fibroblasts and inhibited by miR-101 in hepatocellular carcinoma.
AB  - Vascular mimicry (VM) describes the phenomenon that tumor cells but not
      endothelial cells form vascular-like channels, which provide blood perfusion for
      tumor tissues. VM is associated with tumor growth, metastasis and worse survival
      of different cancers. The mechanisms of VM formation remain largely unknown. We
      showed that the conditioned medium of cancer-associated fibroblast (CM-CAF)
      promoted tumor cells to form capillary-like structure in vitro. Consistently, co
      implantation of CAFs with tumor cells significantly enhanced VM formation in
      mouse xenografts, and higher amount of CAFs was found in VM+ human HCC tissues
      compared to VM- ones. However, the CM-CAF-promoted VM formation was attenuated
      when TGF-beta or SDF1 signaling was abrogated. Similar to CM-CAF, recombinant TGF
      beta1 and SDF1 induced VM formation. We further disclosed that the CAF-secreted
      TGF-beta and SDF1 enhanced the expression of VE-cadherin, MMP2 and laminin5gamma2
      via TGF-betaR1 and CXCR4 in tumor cells, thereby promoted VM formation. Moreover,
      tumor cells with high activity of self-sustaining TGF-beta signaling displayed
      strong capability of VM formation. Subsequent investigations showed that miR-101,
      which was down-regulated in both tumor cells and CAFs, suppressed the CAF
      promoted VM formation in vitro and in vivo. Gain- and loss-of-function analyses
      revealed that miR-101 attenuated TGF-beta signaling transduction by targeting TGF
      betaR1 and Smad2 in tumor cells, and simultaneously abrogated SDF1 signaling by
      suppressing SDF1 expression in CAFs and inhibiting VE-cadherin expression in
      tumor cells. Our findings suggest that the miR-101-TGF-beta/SDF1-VE
      cadherin/MMP2/LAMC2 networks regulate VM formation and represent the potential
      targets for cancer therapy.

PMID- 27693461
TI  - Inhibition of ATR-dependent feedback activation of Chk1 sensitises cancer cells
      to Chk1 inhibitor monotherapy.
AB  - The Chk1 and ATR kinases are critical mediators of the DNA damage response
      pathway and help protect cancer cells from endogenous and oncogene induced
      replication stress. Inhibitors of both kinases are currently being evaluated in
      clinical trials. Chk1 inhibition with V158411 increases DNA damage and activates
      the ATR, ATM and DNA-PKcs dependent DNA damage response pathways. Inhibiting ATR,
      ATM and/or DNA-PKcs has the potential to increase the therapeutic activity of
      Chk1 inhibitors. ATR inhibition but not ATM or DNA-PKcs inhibition potentiated
      the cytotoxicity of V158411 in p53 mutant and wild type human cancer cell lines.
      This increased cytotoxicity correlated with increased nuclear DNA damage and
      replication stress in a dose and time dependent manner. gammaH2AX induction
      following Chk1 inhibition protected cells from caspase-dependent apoptosis.
      Inhibition of ATR increased Chk1 inhibitor induced cell death independently of
      caspase activation. The effect of ATR, ATM and/or DNA-PK inhibition on Chk1
      inhibitor induced replication stress was dependent on the concentration of Chk1
      inhibitor. ATR inhibition potentiated Chk1 inhibitor induced replication stress
      and cytotoxicity via the abrogation of ATR-dependent feedback activation of Chk1
      induced by Chk1 inhibitor generated replication stress. This study suggests that
      combining an ATR inhibitor to lower the threshold by which a Chk1 inhibitor
      induces replication stress, DNA damage and tumour cell death in a wide range of
      cancer types may be a useful clinical approach.

PMID- 27693462
TI  - Ghrelin O-acyltransferase (GOAT) enzyme is overexpressed in prostate cancer, and
      its levels are associated with patient's metabolic status: Potential value as a
      non-invasive biomarker.
AB  - Ghrelin-O-acyltransferase (GOAT) is the key enzyme regulating ghrelin activity,
      and has been proposed as a potential therapeutic target for obesity/diabetes and
      as a biomarker in some endocrine-related cancers. However, GOAT presence and
      putative role in prostate-cancer (PCa) is largely unknown. Here, we demonstrate,
      for the first time, that GOAT is overexpressed (mRNA/protein-level) in prostatic
      tissues (n = 52) and plasma/urine-samples (n = 85) of PCa-patients, compared with
      matched controls [healthy prostate tissues (n = 12) and plasma/urine-samples from
      BMI-matched controls (n = 28), respectively]. Interestingly, GOAT levels in PCa
      patients correlated with aggressiveness and metabolic conditions (i.e. diabetes).
      Actually, GOAT expression was regulated by metabolic inputs (i.e. In1-ghrelin,
      insulin/IGF-I) in cultured normal prostate cells and PCa-cell lines. Importantly,
      ROC-curve analysis unveiled a valuable diagnostic potential for GOAT to
      discriminate PCa at the tissue/plasma/urine-level with high
      sensitivity/specificity, particularly in non-diabetic individuals. Moreover, we
      discovered that GOAT is secreted by PCa-cells, and that its levels are higher in
      urine samples from a stimulated post-massage vs. pre-massage prostate-test. In
      conclusion, plasmatic GOAT levels exhibit high specificity/sensitivity to predict
      PCa-presence compared with other PCa-biomarkers, especially in non-diabetic
      individuals, suggesting that GOAT holds potential as a novel non-invasive PCa
      biomarker.

PMID- 27693464
TI  - Predictive value of sICAM-1 and sVCAM-1 as biomarkers of affective temperaments
      in healthy young adults.
AB  - BACKGROUND: Affective temperaments are intermediate phenotypes for major
      affective disorders and are reported to have a neuroimmune etiopathogenesis. Here
      we investigated the role of soluble intercellular cell adhesion molecule-1 (sICAM
      1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in affective
      temperaments and mood symptoms in healthy adults. METHODS: Healthy adults (n=94)
      were screened for psychiatric disorders using the nonpatient version of the
      Structured Clinical Interview for DSM-IV-I and II. Subjects with medical
      conditions associated with changes in inflammatory response were excluded,
      deriving the final sample (n=68). Affective temperaments were evaluated with
      Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire
      (TEMPS-A). State mood symptoms were assessed using the Young Mania Rating Scale
      and Montgomery-Asberg Depression Rating Scale. Serum sICAM-1 and sVCAM-1 levels
      were measured using enzyme-linked immunosorbent assay. RESULTS: After adjusting
      for confounders (age, gender, BMI, and smoking habits), a high negative
      correlation between depressive and irritable temperament TEMPS-A scores and sVCAM
      1 levels was detected. Although we identified no association between sICAM-1
      levels and affective temperament scores, sICAM-1 was related to the state
      severity of manic symptoms. In a multiple linear regression model, sVCAM-1
      remained a significant predictor of depressive but not irritable temperament
      scores. LIMITATIONS: The temperaments were estimated on the basis of self-report
      questionnaire. CONCLUSIONS: Our findings suggest that sVCAM-1 is related to
      affective temperaments, and it is a trait marker for liability to mood disorders.
      This relationship between alterations in cellular adhesion and affective
      temperament may be important for vulnerability to affective disorders.

PMID- 27693465
TI  - Corrigendum to "Bereavement-related depression: Did the changes induced by DSM-V
      make a difference? Results from a large population-based survey of French
      residents"[J. Affect. Disord. 182 (2015) 82-90].

PMID- 27693463
TI  - Preservation of myocardial fatty acid oxidation prevents diastolic dysfunction in
      mice subjected to angiotensin II infusion.
AB  - RATIONALE: Diastolic dysfunction is a common feature in many heart failure
      patients with preserved ejection fraction and has been associated with altered
      myocardial metabolism in hypertensive and diabetic patients. Therefore, metabolic
      interventions to improve diastolic function are warranted. In mice with a
      germline cardiac-specific deletion of acetyl CoA carboxylase 2 (ACC2), systolic
      dysfunction induced by pressure-overload was prevented by maintaining cardiac
      fatty acid oxidation (FAO). However, it has not been evaluated whether this
      strategy would prevent the development of diastolic dysfunction in the adult
      heart. OBJECTIVE: To test the hypothesis that augmenting cardiac FAO is
      protective against angiotensin II (AngII)-induced diastolic dysfunction in an
      adult mouse heart. METHODS AND RESULTS: We generated a mouse model to induce
      cardiac-specific deletion of ACC2 in adult mice. Tamoxifen treatment (20mg/kg/day
      for 5days) was sufficient to delete ACC2 protein and increase cardiac FAO by 50%
      in ACC2 flox/flox-MerCreMer+ mice (iKO). After 4weeks of AngII (1.1mg/kg/day),
      delivered by osmotic mini-pumps, iKO mice showed normalized E/E' and E'/A' ratios
      compared to AngII treated controls (CON). The prevention of diastolic dysfunction
      in iKO-AngII was accompanied by maintained FAO and reduced glycolysis and
      anaplerosis. Furthermore, iKO-AngII hearts had a~50% attenuation of cardiac
      hypertrophy and fibrosis compared to CON. In addition, maintenance of FAO in iKO
      hearts suppressed AngII-associated increases in oxidative stress and sustained
      mitochondrial respiratory complex activities. CONCLUSION: These data demonstrate
      that impaired FAO is a contributor to the development of diastolic dysfunction
      induced by AngII. Maintenance of FAO in this model leads to an attenuation of
      hypertrophy, reduces fibrosis, suppresses increases in oxidative stress, and
      maintains mitochondrial function. Therefore, targeting mitochondrial FAO is a
      promising therapeutic strategy for the treatment of diastolic dysfunction.

PMID- 27693467
TI  - Expected pairwise congruence among gene trees under the coalescent model.
AB  - Although it is widely appreciated that gene trees may differ from the overall
      species tree and from one another due to various evolutionary processes (e.g.,
      incomplete lineage sorting (ILS), horizontal gene transfer, etc.), the extent of
      this incongruence is rarely quantified and discussed. Here we consider the
      expected amount of incongruence arising from ILS, as modeled by the coalescent
      process. In particular, we compute the probability that two gene trees randomly
      sampled from the same species tree agree with one another as well as the
      distribution of the Robinson-Foulds distance between them, for species trees with
      three to eight taxa. We demonstrate that, as expected under the coalescent model,
      the amount of discordance is affected by species tree-specific factors such as
      speciation times and effective population sizes for the species under
      consideration. Our results highlight the fact that substantial discordance may
      occur, even when the number of species is very small, which has implications both
      for larger taxon samples and for any method that uses estimated gene trees as the
      basis for further statistical inference. The amount of incongruence is
      substantial enough that such methods may need to be modified to account for
      variability in the underlying gene trees.

PMID- 27693466
TI  - Cost-effectiveness of brexpiprazole adjunctive treatment for major depressive
      disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) is a debilitating psychiatric illness
      with a high cost burden. This analysis evaluates the cost-effectiveness of
      adjunctive brexpiprazole versus comparator branded adjunctive treatment for MDD
      and background antidepressant therapy (ADT) alone from a US payer perspective.
      METHODS: An economic model was developed to assess the cost-effectiveness of
      brexpiprazole versus comparator adjunctive treatment and ADT alone on total
      direct medical costs using a 6-week cycle time frame for a total of 48 weeks,
      with treatment response and remission as primary outcomes. The model consisted of
      3 parts, 1 to represent the acute treatment phase and 2 to represent the
      maintenance stage. RESULTS: In the base-case analysis, brexpiprazole as reference
      treatment resulted in cost per additional responder ranging from $19,442-$48,745
      and cost per additional remitter ranging from $27,196-$71,839 versus comparator
      treatments over 48 weeks. Sensitivity analyses showed treatment with
      brexpiprazole was more costly, but more clinically effective in all probabilistic
      simulations. LIMITATIONS: This representation of disease natural history over 48
      weeks may not account for all possible health states. Resource utilization on
      treatment was estimated using the resource use data from previous trials, and may
      overestimate medical costs compared to the real-world setting. Treatment
      comparators were limited to branded therapies, and head-to-head studies were not
      available to obtain data inputs. CONCLUSION: Compared to other branded adjunctive
      therapies, brexpiprazole increases response and remission at 6 weeks; medical
      care cost savings were observed with the use of brexpiprazole. These findings may
      assist clinicians and formulary decision makers when selecting treatment for MDD.

PMID- 27693468
TI  - Parkin regulates lipopolysaccharide-induced proinflammatory responses in acute
      lung injury.
AB  - The acute respiratory distress syndrome (ARDS) is a serious condition resulting
      from direct or indirect lung injury that is associated with high mortality and
      morbidity. A key biological event in the pathogenesis of the acute lung injury
      (ALI) that causes acute respiratory distress syndrome is activation of the lung
      endothelium cells (ECs), which is triggered by a variety of inflammatory insults
      leading to barrier disruption and excessive accumulation of neutrophils.
      Recently, we demonstrated that imatinib protects against lipopolysaccharide (LPS)
      induced EC activation by inhibiting c-Abl kinase. In the present study, we
      explored the role of parkin, a novel c-Abl substrate, in ALI. Parkin is an E3
      ubiquitin ligase originally characterized in the pathogenesis of Parkinson
      disease; however, its potential role in acute inflammatory processes and lung EC
      function remains largely unknown. Using parkin deficient (PARK2-/-) mice, we now
      demonstrate that parkin mediates LPS-induced ALI. After LPS, PARK2-/- mice have
      reduced total protein and cell levels in bronchoalveolar lavage (BAL) compared to
      wild type. Moreover, in LPS-treated PARK2-/- lungs, the sequestration and
      activation of neutrophils and release of inflammatory cytokines (interleukin 6
      [IL-6], tumor necrosis factor alpha [TNF-alpha]) are significantly reduced. The
      BAL levels of soluble VCAM-1 and ICAM-1 are also decreased in LPS-treated PARK2-/
      mice compared to wild type. In cultured human lung endothelial cells,
      downregulation of parkin by small interfering RNA decreases LPS-induced VCAM-1
      expression, IL-8 and IL-6 secretion, and NF-kB phosphorylation. These results
      suggest a previously unidentified role of parkin in mediating endotoxin-induced
      endothelial proinflammatory signaling and indicate that it may play a critical
      role in acute inflammation.

PMID- 27693469
TI  - Cryo-EM structure of respiratory complex I reveals a link to mitochondrial sulfur
      metabolism.
AB  - Mitochondrial complex I is a 1MDa membrane protein complex with a central role in
      aerobic energy metabolism. The bioenergetic core functions are executed by 14
      central subunits that are conserved from bacteria to man. Despite recent progress
      in structure determination, our understanding of the function of the ~30
      accessory subunits associated with the mitochondrial complex is still limited. We
      have investigated the structure of complex I from the aerobic yeast Yarrowia
      lipolytica by cryo-electron microscopy. Our density map at 7.9A resolution
      closely matches the 3.6-3.9A X-ray structure of the Yarrowia lipolytica complex.
      However, the cryo-EM map indicated an additional subunit on the side of the
      matrix arm above the membrane surface, pointing away from the membrane arm. The
      density, which is not present in any previously described complex I structure and
      occurs in about 20 % of the particles, was identified as the accessory sulfur
      transferase subunit ST1. The Yarrowia lipolytica complex I preparation is active
      in generating H2S from the cysteine derivative 3-mercaptopyruvate, catalyzed by
      ST1. We thus provide evidence for a link between respiratory complex I and
      mitochondrial sulfur metabolism.

PMID- 27693470
TI  - Head movement compensation and multi-modal event detection in eye-tracking data
      for unconstrained head movements.
AB  - BACKGROUND: The complexity of analyzing eye-tracking signals increases as eye
      trackers become more mobile. The signals from a mobile eye-tracker are recorded
      in relation to the head coordinate system and when the head and body move, the
      recorded eye-tracking signal is influenced by these movements, which render the
      subsequent event detection difficult. NEW METHOD: The purpose of the present
      paper is to develop a method that performs robust event detection in signals
      recorded using a mobile eye-tracker. The proposed method performs compensation of
      head movements recorded using an inertial measurement unit and employs a multi
      modal event detection algorithm. The event detection algorithm is based on the
      head compensated eye-tracking signal combined with information about detected
      objects extracted from the scene camera of the mobile eye-tracker. RESULTS: The
      method is evaluated when participants are seated 2.6m in front of a big screen,
      and is therefore only valid for distant targets. The proposed method for head
      compensation decreases the standard deviation during intervals of fixations from
      8 degrees  to 3.3 degrees  for eye-tracking signals recorded during large head
      movements. COMPARISON WITH EXISTING METHODS: The multi-modal event detection
      algorithm outperforms both an existing algorithm (I-VDT) and the built-in
      algorithm of the mobile eye-tracker with an average balanced accuracy, calculated
      over all types of eye movements, of 0.90, compared to 0.85 and 0.75, respectively
      for the compared algorithms. CONCLUSIONS: The proposed event detector that
      combines head movement compensation and information regarding detected objects in
      the scene video enables for improved classification of events in mobile eye
      tracking data.

PMID- 27693471
TI  - Serine racemase inhibition induces nitric oxide-mediated neurovascular protection
      during cerebral ischemia.
AB  - There are no effective neuroprotectant drugs for acute cerebral ischemia. Serine
      racemase (SR) synthesizes d-serine, which is involved in N-methyl-d-aspartate
      (NMDA) receptor-induced neurotoxicity. Recently, SR deletion was reported to
      protect against focal cerebral ischemia. However, regulatory mechanisms
      controlling SR-activity in the neurovascular unit (NVU) during cerebral ischemia
      remain to be clarified. We investigated the effects of SR inhibition on
      neurovascular protection after ischemia. The SR inhibitor phenazine methosulfate
      (PMS) alleviated neuronal damage in an ex vivo ischemic model (oxygen glucose
      deprivation [OGD]) using primary neuronal cultures, and in an in vivo mouse model
      of ischemia (middle cerebral artery occlusion [MCAO]). Ischemic preconditioning
      (IP) and PMS-treatment inhibited SR phosphorylation after ischemia ex vivo. In
      addition, SR phosphorylation after MCAO was also decreased in PMS-treated mice.
      Reductions in regional cerebral blood flow (CBF) after MCAO were improved by
      administration of PMS. Treatment with PMS increased phosphorylation of
      endothelial nitric oxide synthase (eNOS) in the ischemic core and penumbra
      region. In neuron-endothelial cell co-cultures, PMS promoted nitric oxide
      production after OGD. These findings indicate that SR inhibition acts as a
      neuroprotectant in the NVU and ameliorant of CBF abnormalities post-stroke. Thus,
      pharmacologic SR inhibition has potential clinical applications.

PMID- 27693472
TI  - Deletion of autophagy-related gene 7 in dopaminergic neurons prevents their loss
      induced by MPTP.
AB  - Parkinson's disease (PD) is a neurodegenerative disease caused by a gradual loss
      of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta
      (SNpc) during aging. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is
      one of the neurotoxins used widely to induce PD-like symptoms in PD animal
      models, including rodents and non-human primates. It has been reported that
      deletion of autophagy-related gene 7 (Atg7) in the brain results in a reduction
      of mDA neurons in adulthood. In this study, we used tyrosine hydroxylase (TH)-Cre
      mice to generate conditional knockout (CKO) mice with the specific deletion of
      Atg7 in mDA neurons. Consistent with previous reports, adult Atg7 CKO mice
      contained fewer TH-positive mDA neurons compared with wild-type (WT) controls. TH
      expressing neurons containing puncta-like structures with p62 and ubiquitin
      immunoreactivity were observed in the midbrain of Atg7 CKO mice but were not
      detected in control mice. However, MPTP-induced loss of mDA neurons was not
      observed in Atg7 CKO mice. Our results indicate that Atg7-involved autophagy is
      required not only for the survival of mDA neurons in the mouse brain, but also
      for MPTP-induced mDA neuron degeneration.

PMID- 27693473
TI  - I can't reach it! Focus on theta sensorimotor rhythm toward a better
      understanding of impaired action-perception coupling.
AB  - It is known that anxiety (ANX) impairs action-perception coupling. This study
      tests whether this impairment could be associated with an alteration of the
      sensorimotor function. To this aim, the cortical activities underlying the
      sensorimotor function were recorded in twelve volunteers in a reach-to-grasp
      paradigm, in which the level of ANX and the position of a glass were manipulated.
      The experimental manipulation of the ANX-related somatosensory state was expected
      to prompt participants to underestimate their reaching-to-grasp capabilities
      while the sensorimotor-related oscillatory brain activities around the 6-Hz
      (theta) frequency over motor-related and parietal regions were expected to be
      modulated. We also investigated the oscillatory brain dynamics around the 11.5-Hz
      (fast-alpha) frequency as a neural hallmark of ANX manipulation induced by the
      breath-restriction. Results indeed showed that participants underestimated their
      reaching-to-grasp maximal performance. Concomittantly, theta-EEG synchronization
      over the motor cortex contralateral to the dominant hand was higher during glass
      presentation under breath-restriction condition (+20.1%; p<0.05), and when the
      glass was perceived as non-reachable (+20.0%; p<0.05). Fast-alpha-EEG
      desynchronization was reduced under breath-restriction (-37.7%; p<0.05). The
      results confirm that ANX-related impairment of action-perception coupling co
      modulates with theta-sensorimotor rhythm. This finding is discussed as an altered
      "readiness state" in the reaching-related cortical network, while individuals are
      anxious.

PMID- 27693475
TI  - Electrophysiological assessment of driving pleasure and difficulty using a task
      irrelevant probe technique.
AB  - The amplitude of event-related brain potentials (ERPs) elicited by task
      irrelevant auditory probes decreases when more attentional resources are
      allocated to a visual task. This task-irrelevant probe technique is considered to
      be useful in assessing the degree of interest in a visual task, as well as task
      difficulty. The present study examined the amplitude of the N1 and P2 components
      elicited by task-irrelevant auditory probes during a driving task in a simulated
      environment. The analysis of ERPs showed that the N1 amplitude decreased when
      participants drove on the road course that had more frequent and sharper curves,
      whereas the P2 amplitude decreased when the road contained sharper curves,
      irrespective of curve frequency. Subjective ratings of driving pleasure and
      difficulty showed the same variation patterns as the N1 and P2 amplitudes,
      respectively. These results suggest that use of the task-irrelevant probe
      technique can assess the degree of driving pleasure and difficulty separately.

PMID- 27693476
TI  - Corrigendum to "The incidence of cholelithiasis after sleeve gastrectomy and its
      association with weight loss: A two-centre retrospective cohort study" [Int. J.
      Surg. 30 (2016) 13-18].

PMID- 27693474
TI  - Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal
      neurons.
AB  - Orexin neurons are known to augment the sympathetic control of cardiovascular
      function, however the role of orexin neurons in parasympathetic cardiac
      regulation remains unclear. To test the hypothesis that orexin neurons contribute
      to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in
      orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents
      in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV).
      Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in
      the lateral hypothalamus resulted in reliable action potential firing as well as
      large whole-cell currents suggesting a strong expression of ChR2 and reliable
      optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV
      elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16
      out of 44 CVNs tested. These responses were heterogeneous and included excitatory
      glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The
      results from this study suggest different sub-population of orexin neurons may
      exert diverse influences on brainstem CVNs and therefore may play distinct
      functional roles in parasympathetic control of the heart.

PMID- 27693477
TI  - Cervical disc arthroplasty for symptomatic cervical disc disease: Traditional and
      Bayesian meta-analysis with trial sequential analysis.
AB  - OBJECTIVE: Cervical disc arthroplasty (CDA) has been designed as a substitute for
      anterior cervical discectomy and fusion (ACDF) in the treatment of symptomatic
      cervical disc disease (CDD). Several researchers have compared CDA with ACDF for
      the treatment of symptomatic CDD; however, the findings of these studies are
      inconclusive. Using recently published evidence, this meta-analysis was conducted
      to further verify the benefits and harms of using CDA for treatment of
      symptomatic CDD. METHODS: Relevant trials were identified by searching the
      PubMed, EMBASE, and Cochrane Library databases. Outcomes were reported as odds
      ratio or standardized mean difference. Both traditional frequentist and Bayesian
      approaches were used to synthesize evidence within random-effects models. Trial
      sequential analysis (TSA) was applied to test the robustness of our findings and
      obtain more conservative estimates. RESULTS: Nineteen trials were included. The
      findings of this meta-analysis demonstrated better overall, neck disability index
      (NDI), and neurological success; lower NDI and neck and arm pain scores; higher
      36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and
      Mental Component Summary (MCS) scores; more patient satisfaction; greater range
      of motion at the operative level; and fewer secondary surgical procedures (all P
      < 0.05) in the CDA group compared with the ACDF group. CDA was not significantly
      different from ACDF in the rate of adverse events (P > 0.05). TSA of overall
      success suggested that the cumulative z-curve crossed both the conventional
      boundary and the trial sequential monitoring boundary for benefit, indicating
      sufficient and conclusive evidence had been ascertained. CONCLUSIONS: For
      treating symptomatic CDD, CDA was superior to ACDF in terms of overall, NDI, and
      neurological success; NDI and neck and arm pain scores; SF-36 PCS and MCS scores;
      patient satisfaction; ROM at the operative level; and secondary surgical
      procedures rate. Additionally, there was no significant difference between CDA
      and ACDF in the rate of adverse events. However, as the CDA procedure is a
      relatively newer operative technique, long-term results and evaluation are
      necessary before CDA is routinely used in clinical practice.

PMID- 27693479
TI  - T-shaped Shunt With Intracavernosal Tunneling for a Pediatric Case of Refractory
      Ischemic Priapism.
AB  - We present the first reported case of refractory pediatric priapism treated by
      intracavernosal tunneling T shunt. A 12-year-old male, with sickle cell disease,
      presented with 72 hours of painful erection. The patient failed conservative
      measures including aspiration, injection of phenylephrine, as well as distal
      shunt procedure. A T-T shunt was performed, as previously described in the adult
      literature. There was immediate resolution of the erection with no complications.
      At 1-year follow-up, he reports no subsequent episodes of priapism and normal
      erections. T shunt with tunneling can be performed in select cases of severe
      pediatric refractory ischemic priapism.

PMID- 27693478
TI  - Dismembered Pyeloplasty in Infants 6 Months Old or Younger With and Without
      External Trans-anastomotic Nephrostent: A Prospective Randomized Study.
AB  - OBJECTIVE: To compare the outcome of dismembered pyeloplasty in infants with and
      without external nephro-ureteric stent (ENUS) for treatment of congenital
      ureteropelvic junction obstruction. METHODS: This is a parallel, randomized
      comparative study between October 2013 and September 2014. Thirty infants <=6
      months old with ureteropelvic junction obstruction indicated for dismembered
      pyeloplasty were randomly assigned (block randomization, closed envelope method)
      into two groups: group A (stentless) and group B (ENUS). Infants with solitary
      kidney, gross pyuria, huge pelvis, vesicoureteric reflux, or other renal
      anomalies were excluded. Operative data, complications, and ultrasonographic and
      nuclear scintigraphy criteria were compared after at least 18 months of follow-up
      using Student t, Mann-Whitney U, Kruskal-Wallis, chi-square, and Fisher exact
      tests when appropriate. Occurrence of urinary leakage was the primary outcome.
      RESULTS: Included patients completed the study with intention-to-treat analysis.
      All children had normal renal function. The mean operative time was 85.3 +/- 6.3
      (60-90) minutes in group A and 92.6 +/- 15.3 (70-120) minutes in group B (P =
      .2). Although there was a significant postoperative improvement in each group in
      split renal function and anterior-posterior renal pelvis diameter, there was no
      significant difference between both groups. The mean hospital stay for group A
      and group B was 5.9 +/- 2 (4-10) days versus 3.5 +/- 0.8 (2-5) days, respectively
      (P < .001). Postoperative urinary leakage was reported only in group A (40%). All
      complications were managed by double J insertion. Auxiliary interventions were
      higher in group A. The overall success rate was 93.4%. Redo pyeloplasty was
      performed in one case in each group. CONCLUSION: ENUS significantly reduces
      hospital stay and complications. It saves the infant hazards of auxiliary
      interventions under general anesthesia for management of leakage or double J
      removal if placed at time of pyeloplasty.

PMID- 27693480
TI  - Calcifying Fibrous Tumor of the Tunica Vaginalis Testis: A Report of 2 Cases.
AB  - OBJECTIVE: To improve the clinical diagnosis and treatment of calcifying fibrous
      tumor (CFT) of the tunica vaginalis testis, we discussed clinical manifestations
      and pathologic features of CFT. MATERIALS AND METHODS: A retrospective analysis
      of 2 cases of CFT that occurred in our hospital was performed, and we also
      reviewed the literature and research reports. RESULTS: Both patients underwent
      local excision with testis preservation surgery, and pathology examination
      confirmed the presence of multiple CFTs of the tunica vaginalis testis.
      CONCLUSION: CFTs are rare, benign multiple lesions, and the recognition of which
      needs to be improved to avoid overtreatment. We are the first to describe 2 cases
      of CFT combined with hepatitis B, but additional studies are needed to confirm
      the relationship between these conditions.

PMID- 27693481
TI  - Gain-of-function mutation in PIK3R1 in a patient with a narrow clinical phenotype
      of respiratory infections.
AB  - Antibody deficiencies can be caused by a variety of defects that interfere with B
      cell development, maturation, and/or function. Using whole-exome sequencing we
      found a PIK3R1 mutation in a patient with hypogammaglobulinemia and a narrow
      clinical phenotype of respiratory infections. Early diagnosis is crucial; careful
      analysis of B and T-cells followed by genetic analyses may help to distinguish
      activated PI3K-delta syndrome (APDS) from other, less severe, predominantly
      antibody deficiencies.

PMID- 27693482
TI  - Experimental evaluation of two different types of reactors for CO2 removal from
      gaseous stream by bottom ash accelerated carbonation.
AB  - Low methane content landfill gas may be enriched by removing carbon dioxide. An
      innovative process, based on carbon dioxide capture and storage by means of
      accelerated carbonation of bottom ash is proposed and studied for the above
      purpose. Within this research framework we devoted a preliminary research
      activity to investigate the possibility of improving the way the contact between
      bottom ash and landfill gas takes place: this is the scope of the work reported
      in this paper. Two different types of reactors - fixed bed and rotating drum -
      were designed and constructed for this purpose. The process was investigated at
      laboratory scale. As the aim of this phase was the comparison of the performances
      of the two different reactors, we used a pure stream of CO2 to preliminarily
      evaluate the reactor behaviors in the most favorable condition for the process
      (i.e. maximum CO2 partial pressure at ambient condition). With respect to the
      simple fixed bed reactor concept, some modifications were proposed, consisting of
      separating the ash bed in three layers. With the three layer configuration we
      would like to reduce the possibility for the gas to follow preferential paths
      through the ash bed. However, the results showed that the process performances
      are not significantly influenced by the multiple layer arrangement. As an
      alternative to the fixed bed reactor, the rotating drum concept was selected in
      order to provide continuous mixing of the solids. Two operating parameters were
      considered and varied during the tests: the filling ratio and the rotating speed.
      Better performances were observed for lower filling ratio while the rotating
      speed showed minor importance. Finally the performances of the two reactors were
      compared. The rotating drum reactor is able to provide improved carbon dioxide
      removal with respect to the fixed bed one, especially when the rotating reactor
      is operated at low filling ratio values and slow rotating speed values. Comparing
      the carbon dioxide specific removal obtained by using the rotating reactor (35
      37g/kgBA), in the best operating conditions, with that measured for the fixed bed
      reactor (21-23g/kgBA), an increase of about 61-66% is observed.

PMID- 27693483
TI  - Adverse effect of valproic acid on an in vitro gastrulation model entails
      activation of retinoic acid signaling.
AB  - Valproic acid (VPA), an antiepileptic drug, is a teratogen that causes neural
      tube and axial skeletal defects, although the mechanisms are not fully
      understood. We previously established a gastrulation model using mouse P19C5 stem
      cell embryoid bodies (EBs), which exhibits axial patterning and elongation
      morphogenesis in vitro. Here, we investigated the effects of VPA on the EB axial
      morphogenesis to gain insights into its teratogenic mechanisms. Axial elongation
      and patterning of EBs were inhibited by VPA at therapeutic concentrations. VPA
      elevated expression levels of various developmental regulators, including Cdx1
      and Hoxa1, known transcriptional targets of retinoic acid (RA) signaling. Co
      treatment of EBs with VPA and BMS493, an RA receptor antagonist, partially
      rescued axial elongation as well as gene expression profiles. These results
      suggest that VPA requires active RA signaling to interfere with EB morphogenesis.

PMID- 27693484
TI  - Molecular analysis of Ixodes rugicollis, Candidatus Neoehrlichia sp. (FU98) and a
      novel Babesia genotype from a European badger (Meles meles).
AB  - The European badger (Meles meles) is a widespread mammal in most countries of the
      European continent, with increasingly recognized veterinary/medical importance
      owing to its preferred habitats (including pastures and urban environments),
      broad spectrum of food items, and role as a game hunting target. However, ticks
      and tick-borne pathogens associated with badgers are only partly known, and most
      of them have not yet been analysed with molecular biological methods The aim of
      this study was to perform molecular taxonomic analysis of ticks collected from a
      road-killed European badger, as well as to molecularly investigate its ticks and
      blood sample for the presence of Anaplasmataceae and piroplasms. Ticks from the
      badger were morphologically identified as females of Ixodes rugicollis. Based on
      its cytochrome oxidase subunit I (COI) and 16S rRNA sequences, I. rugicollis
      phylogenetically clustered together with I. lividus and I. arboricola, i.e. other
      members of the subgenus Pholeoixodes. The blood sample of the badger contained
      the DNA of Candidatus Neoehrlichia sp. (FU98) recently identified in red fox in
      Austria and the Czech Republic. This genotype is most closely related to Ca. N.
      lotoris (from raccoons in North America), and has lower sequence identity with
      the I. ricinus-transmitted zoonotic agent, Ca. N. mikurensis found in Eurasia. In
      the blood of the badger and in one female I. rugicollis, the DNA of a new Babesia
      genotype was also present, which differed from a piroplasm detected in M. meles
      in Spain, and clustered phylogenetically in the B. microti clade. Phylogenetic
      analysis of I. rugicollis (based on two genetic markers) confirms its status in
      subgenus Pholeoixodes. Ca. Neoehrlichia sp. (FU98) was identified for the first
      time in M. meles and in Hungary. In addition, a molecularly previously not yet
      characterized Babesia genotype occurs in badgers in Central Europe.

PMID- 27693485
TI  - PC-FACS.
AB  - PC-FACS(FastArticleCriticalSummaries for Clinicians inPalliativeCare) 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- 27693486
TI  - Extracellular matrix dynamics and functions in the social amoeba Dictyostelium: A
      critical review.
AB  - BACKGROUND: The extracellular matrix (ECM) is a dynamic complex of glycoproteins,
      proteoglycans, carbohydrates, and collagen that serves as an interface between
      mammalian cells and their extracellular environment. Essential for normal
      cellular homeostasis, physiology, and events that occur during development, it is
      also a key functionary in a number of human diseases including cancer. The social
      amoeba Dictyostelium discoideum secretes an ECM during multicellular development
      that regulates multicellularity, cell motility, cell differentiation, and
      morphogenesis, and provides structural support and protective layers to the
      resulting differentiated cell types. Proteolytic processing within the
      Dictyostelium ECM leads to specific bioactive factors that regulate cell motility
      and differentiation. SCOPE OF REVIEW: Here we review the structure and functions
      of the Dictyostelium ECM and its role in regulating multicellular development.
      The questions and challenges that remain and how they can be answered are also
      discussed. MAJOR CONCLUSIONS: The Dictyostelium ECM shares many of the features
      of mammalian and plant ECM, and thus presents an excellent system for studying
      the structure and function of the ECM. GENERAL SIGNIFICANCE: As a genetically
      tractable model organism, Dictyostelium offers the potential to further elucidate
      ECM functions, and to possibly reveal previously unknown roles for the ECM.

PMID- 27693487
TI  - Plasma kisspeptin and ghrelin levels are independently correlated with physical
      activity in patients with anorexia nervosa.
AB  - While physical hyperactivity represents a frequent symptom of anorexia nervosa
      and may have a deleterious impact on the course of the disease, the underlying
      mechanisms are poorly understood. Since several food intake-regulatory hormones
      affect physical activity, the aim of the study was to investigate the association
      of physical activity with novel candidate hormones (kisspeptin, ghrelin,
      oxyntomodulin, orexin-A, FGF-21, R-spondin-1) possibly involved in patients with
      anorexia nervosa. Associations with psychometric parameters and body composition
      were also assessed. We included 38 female anorexia nervosa inpatients (body mass
      index, BMI, mean +/- SD: 14.8 +/- 1.7 kg/m2). Physical activity was evaluated
      using portable armband devices, body composition by bioelectrical impedance
      analysis. Blood withdrawal (hormones measured by ELISA) and psychometric
      assessment of depressiveness (PHQ-9), anxiety (GAD-7), perceived stress (PSQ-20)
      and disordered eating (EDI-2) were performed at the same time. Patients displayed
      a broad spectrum of physical activity (2479-26,047 steps/day) which showed a
      negative correlation with kisspeptin (r = -0.41, p = 0.01) and a positive
      association with ghrelin (r = 0.42, p = 0.01). The negative correlation with
      oxyntomodulin (r = -0.37, p = 0.03) was lost after consideration of potential
      confounders by regression analysis. No correlations were observed between
      physical activity and orexin-A, FGF-21 and R-spondin-1 (p > 0.05). Kisspeptin was
      positively correlated with BMI and body fat mass and negatively associated with
      the interpersonal distrust subscale of the EDI-2 (p < 0.01). Depressiveness,
      anxiety, and perceived stress did not correlate with kisspeptin or any other of
      the investigated hormones (p > 0.05). In conclusion, kisspeptin is inversely and
      ghrelin positively associated with physical activity as measured by daily step
      counts in anorexia nervosa patients suggesting an implication of these peptide
      hormones in the regulation of physical activity in anorexia nervosa.

PMID- 27693488
TI  - Do disinhibited eaters pay increased attention to food cues?
AB  - The Three Factors Eating Questionnaire's measure of disinhibited eating is a
      robust predictor of long-term weight gain. This experiment explored if
      disinhibited eaters display attentional bias to food cues. Participants (N = 45)
      completed a visual dot probe task which measured responses to food (energy dense
      and low energy foods) and neutral cues. Picture pairs were displayed either for a
      100 ms or 2000 ms duration. All participants displayed attentional bias for
      energy dense food items. Indices of attentional bias were largest in disinhibited
      eaters. Attentional bias in disinhibited eaters appeared to be underpinned by
      facilitated attention.

PMID- 27693489
TI  - Food skills confidence and household gatekeepers' dietary practices.
AB  - INTRODUCTION: Household food gatekeepers have the potential to influence the food
      attitudes and behaviours of family members, as they are mainly responsible for
      food-related tasks in the home. The aim of this study was to determine the role
      of gatekeepers' confidence in food-related skills and nutrition knowledge on food
      practices in the home. METHODS: An online survey was completed by 1059 Australian
      dietary gatekeepers selected from the Global Market Insite (GMI) research
      database. Participants responded to questions about food acquisition and
      preparation behaviours, the home eating environment, perceptions and attitudes
      towards food, and demographics. Two-step cluster analysis was used to identify
      groups based on confidence regarding food skills and nutrition knowledge. Chi
      square tests and one-way ANOVAs were used to compare the groups on the dependent
      variables. RESULTS: Three groups were identified: low confidence, moderate
      confidence and high confidence. Gatekeepers in the highest confidence group were
      significantly more likely to report lower body mass index (BMI), and indicate
      higher importance of fresh food products, vegetable prominence in meals, product
      information use, meal planning, perceived behavioural control and overall diet
      satisfaction. Gatekeepers in the lowest confidence group were significantly more
      likely to indicate more perceived barriers to healthy eating, report more time
      constraints and more impulse purchasing practices, and higher convenience
      ingredient use. Other smaller associations were also found. CONCLUSION: Household
      food gatekeepers with high food skills confidence were more likely to engage in
      several healthy food practices, while those with low food skills confidence were
      more likely to engage in unhealthy food practices. Food education strategies
      aimed at building food-skills and nutrition knowledge will enable current and
      future gatekeepers to make healthier food decisions for themselves and for their
      families.

PMID- 27693490
TI  - High-level expression of l-glutamate oxidase in Pichia pastoris using multi-copy
      expression strains and high cell density cultivation.
AB  - l-glutamate oxidase (GLOD), encoded by the gox gene, catalyses the transformation
      of l-glutamic acid into alpha-ketoglutaric acid (alpha-KG). In the present study,
      Pichia pastoris was used for heterologous production of GLOD following
      optimization of the gox coding sequence for expression in the yeast host. A
      series of constructs based on the pHBM905BDM plasmid were engineered and
      transformed into P. pastoris to increase the gox copy number. The results
      indicated that GLOD protein levels and enzyme activity increased with increasing
      gox copy number. Strain PGLOD4, which contained four copies of the target gene,
      was chosen for subsequent fermentation experiments, and a fermentation strategy
      involving two exponential feeding phases was developed. During the preinduction
      phase, glycerol was fed exponentially at MUG = 0.15/h. When the cell density
      reached 300 g/l, methanol was fed exponentially at MUM = 0.03/h to induce GLOD
      production. After 84 h of cultivation, the final cell density and total enzyme
      activity reached 420 g/L and 247.8 U/mL, respectively. The recombinant enzyme
      displayed an optimum temperature of 40  degrees C, which was higher than
      recombinant enzyme expressed in E. coli. This is important because increasing the
      temperature could accelerate enzymatic transformation of l-glutamic acid to alpha
      KG. Experiments also demonstrated superior thermo-stability for the enzyme
      produced in yeast, which further enhances its potential for industrial
      applications.

PMID- 27693491
TI  - Oligo-clonal nanobodies as an innovative targeting agent for cancer therapy: New
      biology and novel targeting systems.
AB  - Variable heavy chain of HcAb (VHH), the smallest intact antibody fragment,
      possesses sub-nanomolar affinity to antigens. In spite of conventional
      antibodies, these fragments recognize concave and linear epitopes. VHHs are one
      the best weapon for targeted drug delivery in nanomedicine and biopharmaceutics.
      HER2 is overexpressed in 20-25% of breast and ovarian cancers. For many reasons,
      HER2 is a prominent target for drug delivery to breast tumor. In this study, we
      designed a robust prokaryotic expression system to express functional VHHs
      against HER2 receptor. This system showed high recombinant yields besides
      purified VHHs flow cytometry verified great capabilities of these molecules to
      pinpoint ecto-domain of HER2 receptor in MC4L2 HER2+ while insignificant non
      specific binding to MC4L2 HER2-confirm nanobodies trivial cross-reaction. In the
      next step, we evaluated cooperative effect of four distinctive VHHs (oligoclonal
      VHHs) targeting different epitopes on HER2. As our result proved, using
      oligoclonal nanobodies as targeting moiety enhance targeting efficacy in
      comparison with monoclonal VHH.

PMID- 27693492
TI  - CVD 103-HgR vaccine for travelers.

PMID- 27693493
TI  - miR-1207-3p regulates the androgen receptor in prostate cancer via
      FNDC1/fibronectin.
AB  - Prostate cancer (PCa) is frequently diagnosed in men, and dysregulation of
      microRNAs is characteristic of many cancers. MicroRNA-1207-3p is encoded at the
      non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an
      established PCa susceptibility locus. However, the role of microRNA-1207-3p in
      PCa is unclear. We discovered that microRNA-1207-3p is significantly
      underexpressed in PCa cell lines in comparison to normal prostate epithelial
      cells. Increased expression of microRNA-1207-3p in PCa cells significantly
      inhibits proliferation, migration, and induces apoptosis via direct molecular
      targeting of FNDC1, a protein which contains a conserved protein domain of
      fibronectin (FN1). FNDC1, FN1, and the androgen receptor (AR) are significantly
      overexpressed in PCa cell lines and human PCa, and positively correlate with
      aggressive PCa. Prostate tumor FN1 expression in patients that experienced PCa
      specific death is significantly higher than in patients that remained alive.
      Furthermore, FNDC1, FN1 and AR are concomitantly overexpressed in metastatic PCa.
      Consequently, these studies have revealed a novel microRNA-1207-3p/FNDC1/FN1/AR
      regulatory pathway in PCa.

PMID- 27693494
TI  - Bradykinin promotes migration and invasion of hepatocellular carcinoma cells
      through TRPM7 and MMP2.
AB  - Tumor metastasis is the main reason of death for hepatocellular carcinoma (HCC)
      patients. Cell migration and invasion are two prerequisites for tumor metastasis,
      in which TRPM7 and MMPs play an important role. In our study, we found that
      bradykinin (BK) could upregulate the expression of TRPM7 and dynamically regulate
      the phosphorylation of non-muscle myosin IIA heavy chain (NMHC-IIA) Ser-1943 in
      HepG2 cells. The influx of Ca2+ via TRPM7 was necessary for elevating the
      activity of m-calpain and MU-calpain. Additionally, we observed that BK
      stimulated HepG2 cells to secrete more MMP2 but not MMP9. Src was critical in the
      process of MMP2 secretion and invadopodia formation. The heat map showed that
      BDKRB2, TRPM7 and MMP2 had higher overexpression proportions in 25 HCC cell
      lines. Some clinical specimens of HCC also indicated that BDKRB2 and MMP2 were
      overexpressed. In conclusion, BK promoted migration and invasion of HCC cells
      through TRPM7 and MMP2.

PMID- 27693495
TI  - Downregulation of miR-199b promotes the acute spinal cord injury through IKKbeta
      NF-kappaB signaling pathway activating microglial cells.
AB  - Inflammatory response played an important role in the progression of spinal cord
      injury (SCI). Several miRNAs were associated with the pathology of SCI. However,
      the molecular mechanism of miRNA involving in inflammatory response in acute SCI
      (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2
      groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of
      miR-199b and IkappaB kinase beta-nuclear factor-kappa B (IKKbeta-NF-kappaB)
      signaling pathway were evaluated by quantitative reverse transcription-PCR (qRT
      PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide
      (LPS). We found that downregulation of miR-199b and activation of IKKbeta/NF
      kappaB were observed in rats after ASCI and in activated microglia. miR-199b
      negatively regulated IKKbeta by targeting its 3'- untranslated regions (UTR)
      through using luciferase reporter assay. Overexpression of miR-199b reversed the
      up-regulation of IKKbeta, p-p65, tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) in LPS-treated BV2 cells assessed by western
      blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of
      miR-199b inhibitor on the expression of TNF-alpha and IL-1beta. In the SCI rats,
      overexpression of miR-199b attenuated ASCI and decreased the expression of
      IKKbeta-NF-kappaB signaling pathway and TNF-alpha and IL-1beta. These results
      indicated that miR-199b attenuated ASCI at least partly through IKKbeta-NF-kappaB
      signaling pathway and affecting the function of microglia. Our findings suggest
      that miR-199b may be employed as therapeutic for spinal cord injury.

PMID- 27693496
TI  - Ossification of the posterior ligament is mediated by osterix via inhibition of
      the beta-catenin signaling pathway.
AB  - Ossification of the posterior longitudinal ligament (OPLL) involves ectopic
      calcification of the spinal ligament preferentially at the cervical spine. OPLL
      is associated with different diseases and occurs by endochondral ossification,
      which is associated with the activity of different transcription factors.
      However, the pathogenesis of OPLL remains unclear. Here, we investigated the role
      of osterix (Osx), a transcription factor that functions downstream of Runx2 and
      is an important regulator of osteogenesis, in the process of OPLL in a
      dexamethasone (Dex)-induced model of spinal ligament ossification. Our results
      showed that Osx is upregulated in patients with OPLL and during the ossification
      of ligament cells in parallel with the upregulation of osteogenic markers
      including osteocalcin (OCN), alkaline phosphatase (ALP) and collagen-1 (Col-1).
      Dex-induced ossification of ligament cells was associated with the downregulation
      and inactivation of beta-catenin, and these effects were offset by Osx knockdown.
      Activation of beta-catenin signaling abolished the effect of Dex on ossification
      and the upregulation of osteogenic markers. Taken together, our results suggest
      that OPLL is mediated by Osx via a mechanism involving the Wnt/beta-catenin
      signaling pathway, providing a basis for further research to identify potential
      targets for the treatment of OPLL.

PMID- 27693497
TI  - Abscisic Acid Catabolism Generates Phaseic Acid, a Molecule Able to Activate a
      Subset of ABA Receptors.

PMID- 27693498
TI  - The pulmonary phagocytosis response to separate and combined impacts of manganese
      (IV) and chromium (VI) containing particulates.
AB  - We investigated by the optical microscopy some cytological characteristics of the
      bronchoalveolar lavage fluid cell population 24h after intratracheal instillation
      of microscale MnO2 and BaCrO4 particles (separately or together at two different
      doses) into the lungs of Wistar rats. Besides, the cytotoxicity of both
      particulates for rat peritoneal macrophages in vitro was assessed by the trypan
      blue exclusion test and proved significant. They were found to evoke a typical
      dose-dependent pulmonary phagocytosis response usually observed under inhalation
      or intratracheal impacts of low-soluble mineral and metal particles. A
      significant shift in the above mentioned cell population toward the prevalence of
      neutrophllic leukocytes (NL) over alveolar macrophages (AM) proved once more to
      be the most characteristic feature of this response. Although the particle load
      of a unit AM was always higher than that of a unit NL, the collective
      contribution of the recruited NLs to the total particles internalization by both
      AMs and NLs together was quite significant. This fact confirms that NL
      recruitment is an important auxiliary mechanism of the cytotoxic particle
      elimination from lungs compensating for the macrophage damage caused by them.
      Well adjusted functioning of this compensatory mechanism was additionally
      demonstrated by isobolographic analysis based on the Response Surface
      Methodology. On the other hand, this analysis confirmed that the type of combined
      toxicity depends on a particular effect this type is assessed for and on the
      effect's dose-dependent level.

PMID- 27693499
TI  - Integrating in silico models to enhance predictivity for developmental toxicity.
AB  - Application of in silico models to predict developmental toxicity has
      demonstrated limited success particularly when employed as a single source of
      information. It is acknowledged that modelling the complex outcomes related to
      this endpoint is a challenge; however, such models have been developed and
      reported in the literature. The current study explored the possibility of
      integrating the selected public domain models (CAESAR, SARpy and P&G model) with
      the selected commercial modelling suites (Multicase, Leadscope and Derek Nexus)
      to assess if there is an increase in overall predictive performance. The results
      varied according to the data sets used to assess performance which improved upon
      model integration relative to individual models. Moreover, because different
      models are based on different specific developmental toxicity effects,
      integration of these models increased the applicable chemical and biological
      spaces. It is suggested that this approach reduces uncertainty associated with in
      silico predictions by achieving a consensus among a battery of models. The use of
      tools to assess the applicability domain also improves the interpretation of the
      predictions. This has been verified in the case of the software VEGA, which makes
      freely available QSAR models with a measurement of the applicability domain.

PMID- 27693500
TI  - Tribological rehydration of cartilage and its potential role in preserving joint
      health.
AB  - OBJECTIVE: During exercise, cartilage recovers interstitial fluid lost during
      inactivity, which explains how tissue thickness and joint space are maintained
      over time. This recovery phenomenon is currently explained by a combination of
      osmotic swelling during intermittent bath exposure and sub-ambient pressurization
      during unloading. This paper tests an alternate hypothesis that cartilage can
      retain and recover interstitial fluid in the absence of bath exposure and
      unloading when physiological hydrodynamics are present. METHOD: Stationary
      cartilage-on-flat experiments were conducted to eliminate intermittent bath
      exposure as a potential contributor to fluid uptake. In situ compression
      measurements were used to monitor the loss, retention, and recovery of
      interstitial fluid during testing in saline. Samples were left larger than the
      contact area to preserve a convergence zone for hydrodynamic pressurization.
      RESULTS: Interstitial fluid lost during static loading was recovered during
      sliding in the absence of unloading and contact migration; fluid recovery in a
      stationary contact cannot be explained by biphasic theory and suggests a
      fundamentally new contributor to the recovery process. We call the phenomenon
      'tribological rehydration' because recovery was induced by sliding rather than by
      unloading or migration. Sensitivities to sliding speed, surface permeability, and
      nature of the convergence wedge are consistent with the hypothesis that
      hydrodynamic effects underlie the tribological rehydration phenomenon.
      CONCLUSIONS: This study demonstrates that cartilage can retain and recover
      interstitial fluid without migration or unloading. The results suggest that
      hydrodynamic effects in the joint are not only important contributors to
      lubrication, they are likely equally important to the preservation of joint
      space.

PMID- 27693502
TI  - Vitamin E protects rat mesenchymal stem cells against hydrogen peroxide-induced
      oxidative stress in vitro and improves their therapeutic potential in surgically
      induced rat model of osteoarthritis.
AB  - OBJECTIVE: Oxidative stress is a major obstacle against cartilage repair in
      osteoarthritis (OA). Anti-oxidant agents can play a vital role in addressing this
      issue. We evaluated the effect of Vitamin E preconditioning in improving the
      potential of mesenchymal stem cells (MSCs) to confer resistance against oxidative
      stress prevailing during OA. METHODS: Vitamin E pretreated MSCs were exposed to
      oxidative stress in vitro by hydrogen peroxide (H2O2) and also implanted in
      surgically-induced rat model of OA. Analysis was done in terms of cell
      proliferation, apoptosis, cytotoxicity, chondrogenesis and repair of cartilage
      tissue. RESULTS: Vitamin E pretreatment enabled MSCs to counteract H2O2-induced
      oxidative stress in vitro. Proliferative markers, proliferating cell nuclear
      antigen (PCNA) and Ki67 were up-regulated, along with the increase in the
      viability of MSCs. Expression of transforming growth factor-beta (TGFbeta) was
      also increased. Reduction of apoptosis, expression of vascular endothelial growth
      factor (VEGF) and caspase 3 (Casp3) genes, and lactate dehydrogenase (LDH)
      release were also observed. Transplantation of Vitamin E pretreated MSCs resulted
      in increased proteoglycan contents of cartilage matrix. Increased expression of
      chondrogenic markers, Aggrecan (Acan) and collagen type-II alpha (Col2a1)
      accompanied by decreased expression of collagen type-I alpha (Col1a1) resulted in
      increased differentiation index that signifies the formation of hyaline
      cartilage. Further, there was an increased expression of PCNA and TGFbeta genes
      along with a decreased expression of Casp3 and VEGF genes with increased
      histological score. CONCLUSION: Taken together results of this study demonstrated
      that Vitamin E pretreated MSCs have an improved ability to impede the progression
      of OA and thus increased potential to treat OA.

PMID- 27693501
TI  - Suppression of Sestrins in aging and osteoarthritic cartilage: dysfunction of an
      important stress defense mechanism.
AB  - OBJECTIVES: Aging is an important osteoarthritis (OA) risk factor and compromised
      stress defense responses may mediate this risk. The Sestrins (Sesn) promote cell
      survival under stress conditions and regulate AMP-activated protein kinase (AMPK)
      and mammalian target of rapamycin (mTOR) signaling. This study examined Sesn
      expression in normal and OA cartilage and functions of Sesn in chondrocytes.
      METHODS: Sesn expression in human and mouse normal and OA cartilage was analyzed
      by quantitative polymerase chain reaction (PCR) and immunohistochemistry. Sesn
      function was investigated by using small interfering RNA (siRNA) mediated Sesn
      knockdown and overexpression with analysis of cell survival, gene expression,
      autophagy, and AMPK and mTOR activation. RESULTS: Sesn mRNA levels were
      significantly reduced in human OA cartilage and immunohistochemistry of human and
      mouse OA cartilage also showed a corresponding reduction in protein levels. In
      cultured human chondrocytes Sesn1, 2 and 3 were expressed and increased by
      tunicamycin, an endoplasmic reticulum (ER) stress response inducer and 2
      deoxyglucose (2DG), a metabolic stress inducer. Sesn1 and 2 were increased by
      tBHP, an oxidative stress inducer. Sesn knockdown by siRNA reduced chondrocyte
      viability under basal culture conditions and in the presence of 2DG. Sesn
      overexpression enhanced LC3-II formation and autophagic flux, and this was
      related to changes in mTOR but not AMPK activation. CONCLUSION: These findings
      are the first to show that Sesn expression is suppressed in OA affected
      cartilage. Sesn support chondrocyte survival under stress conditions and promote
      autophagy activation through modulating mTOR activity. Suppression of Sesn in OA
      cartilage contributes to deficiency in an important cellular homeostasis
      mechanism.

PMID- 27693503
TI  - Anterior knee pain following anterior cruciate ligament reconstruction does not
      increase the risk of patellofemoral osteoarthritis at 15- and 20-year follow-ups.
AB  - OBJECTIVE: To prospectively evaluate the relationship between the presence or
      persistence of anterior knee pain (AKP) during the first 2-years following
      anterior cruciate ligament reconstruction (ACLR) and patellofemoral
      osteoarthritis (PFOA) at 15- and 20-years. DESIGN: This study was ancillary to a
      long-term prospective cohort study of 221 participants following bone-patellar
      tendon-bone ACLR. AKP was assessed at 1- and 2-years post-ACLR using part of the
      Cincinnati knee score with an additional pain location question (persistence
      defined as presence at both follow-ups). Radiographic PFOA (definite
      patellofemoral osteophyte) and symptomatic PFOA (patellofemoral osteophyte, with
      knee pain during past 4 weeks) was assessed at 15- and 20-years follow-up. We
      used generalized linear models with Poisson regression to assess the relationship
      between AKP and PFOA. RESULTS: Of the 181 participants (82%) who were assessed at
      15-years post-ACLR (age 39 +/- 9 years; 42% female), 36 (24%) and 33 (22%) had
      AKP at 1- and 2-years, respectively, while 14 (8%) reported persistent AKP.
      Radiographic and symptomatic PFOA was observed at 15-years in 130 (72%) and 70
      (39%) participants, respectively, and at 20-years in 115 (80%) and 60 (42%)
      participants, respectively. Neither the presence nor persistence of AKP at 1-
      and/or 2-years post-ACLR was associated with significantly higher risk of
      radiographic or symptomatic PFOA at 15- or 20-years (risk ratios <2.1).
      CONCLUSIONS: Although AKP and PFOA were prevalent, AKP does not appear to be
      associated with long-term PFOA following ACLR.

PMID- 27693504
TI  - Relative left frontal activity in reappraisal and suppression of negative
      emotion: Evidence from frontal alpha asymmetry (FAA).
AB  - Previous studies have shown that reappraisal (changing the way that one thinks
      about emotional events) is an effective strategy for regulating emotion, compared
      with suppression (reducing emotion-expressive behavior). In the present study, we
      investigated relative left frontal activity when participants were instructed to
      use reappraisal and suppression of negative emotion, by measuring frontal alpha
      asymmetry (FAA). Two electroencephalography (EEG) experiments were conducted; FAA
      was analyzed while 102 healthy participants (59 men, 43 women) watched negative
      images after being instructed to perform reappraisal (Experiment 1) and
      suppression (Experiment 2). Habitual use of reappraisal and suppression was also
      assessed using the emotion regulation questionnaire (ERQ). The results of
      Experiment 1 showed that relative left frontal activity was greater when
      instructed to use reappraisal of negative images than when normally viewing
      negative images. In contrast, we observed no difference between conditions of
      instructed suppression and normal viewing in Experiment 2. In addition, in male
      participants, habitual use of reappraisal was positively correlated with
      increased relative left frontal activity for instructed reappraisal, while
      habitual use of suppression did not show a significant correlation with changes
      in relative left frontal activity for instructed suppression. These results
      suggest that emotional responses to negative images might be decreased for
      instructed reappraisal, but not suppression. These findings support previous
      reports that reappraisal is an effective emotion regulation strategy, compared
      with suppression.

PMID- 27693505
TI  - Drug resistance in ALK-positiveNon-small cell lungcancer patients.
AB  - Patients are diagnosed as anaplastic lymphoma kinase (ALK) positive, i.e.
      exhibiting the ALK rearrangement, and comprise 3-7% of non-small-cell lung cancer
      (NSCLC) cases. Three generations of ALK inhibitors have been developed and used
      in targeted therapy, although there are still improving spaces of drug resistance
      at the initiation of each treatment. The current review discusses the
      pathophysiology of ALK-positive NSCLC and the role of three generations of ALK
      target inhibitors including crizotinib, ceritinib, alectinib and lorlatinib, as
      well as the mechanisms of the secondary resistance. We mainly focused on the
      point mutations that are the most important resistance-producing mechanism and
      most common form caused by each inhibitor. In addition, we examine the three
      dimensional structure of ALK to understand the functional impact of these
      mutations and analyse the underlying molecular mechanisms of the resistance to
      each generation of ALK inhibitor to benefit the selection decision of the most
      rational therapy and improve therapeutic effects to the disease.

PMID- 27693507
TI  - Cell-Intrinsic Adaptation Arising from Chronic Ablation of a Key Rho GTPase
      Regulator.
AB  - Genome-editing technologies allow systematic inactivation of human genes. Whether
      knockout phenotypes always reflect gene functions as determined by acute RNAi is
      an important question. Here we show how the acute knockdown of the Adams-Oliver
      syndrome (AOS) gene DOCK6, coding for a RAC1/CDC42 guanine nucleotide exchange
      factor, results in strikingly different phenotypes to those generated by genomic
      DOCK6 disruption. Cell-intrinsic adaptation compensates for loss of DOCK6
      function. Prolonged DOCK6 loss impacts upon the MRTF-A/SRF transcription factor,
      reducing levels of the ubiquitin-like modifier ISG15. Reduced ISGylation of the
      IQGAP1 protein increases levels of active CDC42 and RAC1 to compensate for DOCK6
      disruption. Similar downregulation of ISG15 in cells from DOCK6 AOS patients
      indicates that such adaptation can compensate for genetic defects during
      development. Thus, phenotypes of gene inactivation are critically dependent on
      the timescale, as acute knockdown reflects a transient state of adjustment to a
      new equilibrium that is attained following compensation.

PMID- 27693506
TI  - TRIMs and Galectins Globally Cooperate and TRIM16 and Galectin-3 Co-direct
      Autophagy in Endomembrane Damage Homeostasis.
AB  - Selective autophagy performs an array of tasks to maintain intracellular
      homeostasis, sterility, and organellar and cellular functionality. The fidelity
      of these processes depends on precise target recognition and limited activation
      of the autophagy apparatus in a localized fashion. Here we describe cooperation
      in such processes between the TRIM family and Galectin family of proteins. TRIMs,
      which are E3 ubiquitin ligases, displayed propensity to associate with Galectins.
      One specific TRIM, TRIM16, interacted with Galectin-3 in a ULK1-dependent manner.
      TRIM16, through integration of Galectin- and ubiquitin-based processes,
      coordinated recognition of membrane damage with mobilization of the core
      autophagy regulators ATG16L1, ULK1, and Beclin 1 in response to damaged
      endomembranes. TRIM16 affected mTOR, interacted with TFEB, and influenced TFEB's
      nuclear translocation. The cooperation between TRIM16 and Galectin-3 in targeting
      and activation of selective autophagy protects cells from lysosomal damage and
      Mycobacterium tuberculosis invasion.

PMID- 27693508
TI  - Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic
      ATG5 Expression in Neurons.
AB  - Autophagy is a cytoplasmic degradation system that is important for starvation
      adaptation and cellular quality control. Previously, we reported that Atg5-null
      mice are neonatal lethal; however, the exact cause of their death remains
      unknown. Here, we show that restoration of ATG5 in the brain is sufficient to
      rescue Atg5-null mice from neonatal lethality. This suggests that neuronal
      dysfunction, including suckling failure, is the primary cause of the death of
      Atg5-null neonates, which would further be accelerated by nutrient insufficiency
      due to a systemic failure in autophagy. The rescued Atg5-null mouse model, as a
      resource, allows us to investigate the physiological roles of autophagy in the
      whole body after the neonatal period. These rescued mice demonstrate previously
      unappreciated abnormalities such as hypogonadism and iron-deficiency anemia.
      These observations provide new insights into the physiological roles of the
      autophagy factor ATG5.

PMID- 27693509
TI  - The CAMSAP3-ACF7 Complex Couples Noncentrosomal Microtubules with Actin Filaments
      to Coordinate Their Dynamics.
AB  - For adaptation to complex cellular functions, dynamic cytoskeletal networks are
      required. There are two major components of the cytoskeleton, microtubules and
      actin filaments, which form an intricate network maintaining an exquisite
      cooperation to build the physical basis for their cellular function. However,
      little is known about the molecular mechanism underlying their synergism. Here,
      we show that in Caco2 epithelial cells, noncentrosomal microtubules crosstalk
      with F-actin through their minus ends and contribute to the regulation of focal
      adhesion size and cell migration. We demonstrate that ACF7, a member of the
      spectraplakin family of cytoskeletal crosslinking proteins, interacts with Nezha
      (also called CAMSAP3) at the minus ends of noncentrosomal microtubules and
      anchors them to actin filaments. Those noncentrosomal microtubules cooperate with
      actin filaments through retrograde flow to keep their length and orientation
      perpendicular to the cell edge as well as regulate focal adhesion size and cell
      migration.

PMID- 27693510
TI  - Characterization of novel dystonia musculorum mutant mice: Implications for
      central nervous system abnormality.
AB  - We identified a novel spontaneous mutant mouse showing motor symptoms that are
      similar to those of the dystonia musculorum (dt) mouse. The observations
      suggested that the mutant mice inherited the mild dt phenotype as an autosomal
      recessive trait. Linkage analysis showed that the causative gene was located near
      D1Mit373 and D1Mit410 microsatellite markers on chromosome 1, which are close to
      the dystonin (Dst) gene locus. To investigate whether Dst is the causative gene
      of the novel mutant phenotype, we crossed the mutant with Dst gene trap (DstGt)
      mice. Compound heterozygotes showed a typical dt phenotype with sensory
      degeneration and progressive motor symptoms. DNA sequencing analysis identified a
      nonsense mutation within the spectrin repeats of the plakin domain. The novel
      mutant allele was named dt23Rbrc. Motor abnormalities in homozygous
      dt23Rbrc/dt23Rbrc mice are not as severe as homozygous DstGt/DstGt mice.
      Histological analyses showed abnormal neurofilament (NF) accumulation in the
      nervous system of homozygous dt23Rbrc/dt23Rbrc mice, which is characteristic of
      the dt phenotype. We mapped the distribution of abnormal NF-accumulated neurons
      in the brain and found that they were located specifically in the brainstem,
      spinal cord, and in regions such as the vestibular nucleus, reticular nucleus,
      and red nucleus, which are implicated in posture and motor coordination pathways.
      The quantification of abnormal NF accumulation in the cytoplasm and spheroids
      (axons) of neurons showed that abnormal NF immunoreactivity was lower in
      homozygous dt23Rbrc/dt23Rbrc mice than in homozygous DstGt/DstGt mice. Therefore,
      we have identified a novel hypomorphic allele of dt, which causes histological
      abnormalities in the central nervous system that may account for the abnormal
      motor phenotype. This novel spontaneously occurring mutant may become a good
      model of hereditary sensory and autonomic neuropathy type 6, which is caused by
      mutations in the human DST gene.

PMID- 27693512
TI  - Cutaneous microvascular reactivity and aortic elasticity in coronary artery
      disease: Comparison of the laser Doppler flowmetry and echocardiography.
AB  - BACKGROUND AND AIM: Decreased vascular reactivity in atherosclerosis was
      previously shown. In our study, it was aimed to demonstrate the decreased
      vascular functions in both microvascular and macrovascular tissues and to
      estimate any correlation between them. METHODS: Twenty-five control outpatients
      with no coronary artery disease (CAD) history and 26 outpatients with CAD history
      were enrolled in the study. Local cutaneous post-occlusive reactive hyperemia
      (PORH) responses after three minutes of brachial occlusion with a pneumatic cuff
      were recorded noninvasively by a Perimed Periflux 5010 laser Doppler flow system.
      Aortic distensibility and stiffness indexes were recorded noninvasively by a two
      dimensional Doppler echocardiography machine (Vivid S6 GE Medical System, Horten,
      Norway). RESULTS: Except for the medication history of subjects, there were no
      significant demographic differences between the CAD and control groups. Peak flow
      (PF), resting flow (RF) and biological zero(BZ) laser Doppler measurements were
      not decreased, but PF-RF/RF (%), PF-BZ/BF (%), hyperemia repayment and PORH
      indexes were significantly decreased in the CAD group (P=0.005, P=0.024, P=0.017,
      P=0.006, respectively) with laser Doppler measurements. Aortic strain (%) and
      aortic distensibility (cm3/dyn-1) measurements were significantly decreased in
      the CAD group (P=0.005, P=0.013). However, there was no correlation between
      microvascular indexes (hyperemia repayment index, PORH index) and macrovascular
      indexes (aortic strain and aortic distensibility). DISCUSSION: Different
      corrupted vascular tonus regulator systems in arteries of varying diameter,
      different major reactive responses to the stimuli or, finally, the lack of a
      number of subjects to obtain a significant level may be responsible for the
      irrelevant correlation analysis. CONCLUSION: The differences in arterial beds
      (both aorta and microcirculation) may be examined to assess the cardiovascular
      risk in patients with history of CAD.

PMID- 27693513
TI  - Diagnostic utility of fractional exhaled nitric oxide in prolonged and chronic
      cough according to atopic status.
AB  - BACKGROUND: Cough-variant asthma (CVA) and cough-predominant asthma (CPA) are the
      major causes of persistent cough in Japan. The utility of fractional exhaled
      nitric oxide (FeNO) measurement in the differential diagnosis of persistent cough
      has been reported, but the influence of atopic status, which is associated with
      higher FeNO levels, on the diagnostic utility of FeNO has been unknown. METHODS:
      We retrospectively analyzed 105 non-smoking patients with prolonged and chronic
      cough that were not treated with corticosteroids and anti-leukotrienes. RESULTS:
      CPA was diagnosed in 37 patients, CVA in 40, and non-asthmatic cough (NAC) in 28.
      FeNO levels were significantly higher in the CPA [35.8 (7.0-317.9) ppb] and CVA
      [24.9 (3.1-156.0) ppb] groups than in the NAC group [18.2 (6.9-49.0) ppb] (p <
      0.01 by Kruskal-Wallis test). The optimal cut-off for distinguishing asthmatic
      cough (AC; CPA and CVA) from NAC was 29.2 ppb [area under the curve (AUC) 0.74, p
      < 0.01]. Ninety-one percent of subjects with FeNO levels >=29.2 ppb had AC.
      Meanwhile, 40% of AC patients had FeNO levels <29.2 ppb. Stratified cut-off
      levels were 31.1 ppb (AUC 0.83) in atopic subjects vs. 19.9 ppb (AUC 0.65) in non
      atopic subjects (p = 0.03 for AUC). CONCLUSIONS: Although high FeNO levels
      suggested the existence of AC, lower FeNO levels had limited diagnostic
      significance. Atopic status affects the utility of FeNO levels in the
      differential diagnosis of prolonged and chronic cough.

PMID- 27693511
TI  - Infection of Hepatocytes With HCV Increases Cell Surface Levels of Heparan
      Sulfate Proteoglycans, Uptake of Cholesterol and Lipoprotein, and Virus Entry by
      Up-regulating SMAD6 and SMAD7.
AB  - BACKGROUND & AIMS: The signaling molecule and transcriptional regulator SMAD6,
      which inhibits the transforming growth factor beta signaling pathway, is required
      for infection of hepatocytes by hepatitis C virus (HCV). We investigated the
      mechanisms by which SMAD6 and another inhibitory SMAD (SMAD7) promote HCV
      infection in human hepatoma cells and hepatocytes. METHODS: We infected Huh7 and
      Huh7.5.1 cells and primary human hepatocytes with Japanese fulminant hepatitis-1
      (JFH1) HCV cell culture system (HCVcc). We then measured HCV binding,
      intracellular levels of HCV RNA, and expression of target genes. We examined HCV
      entry in HepG2/microRNA (miR) 122/CD81 cells, which support entry and replication
      of HCV, were transfected these cells with small interfering RNAs targeting
      inhibitory SMADs to analyze gene expression profiles. Uptake of labeled low
      density lipoprotein (LDL) and cholesterol was measured. Cell surface proteins
      were quantified by flow cytometry. We obtained liver biopsy samples from 69
      patients with chronic HCV infection and 19 uninfected individuals (controls) and
      measured levels of syndecan 1 (SDC1), SMAD7, and SMAD6 messenger RNAs (mRNAs).
      RESULTS: Small interfering RNA knockdown of SMAD6 blocked the binding and
      infection of hepatoma cell lines and primary human hepatocytes by HCV, whereas
      SMAD6 overexpression increased HCV infection. We found levels of mRNAs encoding
      heparan sulfate proteoglycans (HSPGs), particularly SDC1 mRNA, and cell surface
      levels of heparan sulfate to be reduced in cells after SMAD6 knockdown. SMAD6
      knockdown also reduced transcription of genes encoding lipoprotein and
      cholesterol uptake receptors, including the LDL receptor (LDLR), the very LDLR,
      and the scavenger receptor class B member 1 in hepatocytes; knockdown of SMAD6
      also inhibited cell uptake of cholesterol and lipoprotein. Overexpression of
      SMAD6 increased the expression of these genes. Similar effects were observed with
      knockdown and overexpression of SMAD7. In addition, HCV infection of cells
      increased the expression of SMAD6, which required the activity of nuclear factor
      kappaB, but not transforming growth factor beta. Liver tissues from patients with
      chronic HCV infection had significantly higher levels of SMAD6, SMAD7, and HSPG
      mRNAs than controls. CONCLUSIONS: In studies of hepatoma cell lines and primary
      human hepatocytes, we found that infection with HCV leads to activation of
      nuclear factor-kappaB, resulting in increased expression of SMAD6 and SMAD7. Up
      regulation of SMAD6 and SMAD7 induces the expression of HSPGs, such as SDC1, as
      well as LDLR, very LDLR, and the scavenger receptor class B member 1, which
      promote HCV entry and propagation, as well as cellular uptake of cholesterol and
      lipoprotein.

PMID- 27693514
TI  - Hepatectomy for patients with alveolar echinococcosis: Long-term follow-up
      observations of 144 cases.
AB  - BACKGROUND: Western China is a region in which alveolar echinococcosis (AE) is
      endemic. Few studies and comparisons have evaluated the outcomes of AE patients
      after hepatectomy, and no strategy has been defined for the treatment of AE
      patients with unresectable tumors. This study sought to assess the outcomes of AE
      patients after hepatectomy at a tertiary referral center. PATIENTS AND METHODS:
      We retrospectively analyzed data from 144 patients with hepatic AE who were
      treated via hepatectomy at our center between January 2004 and December 2015.
      Patients' overall survival (OS), progression-free survival (PFS), and risk
      factors were analyzed, and Kaplan-Meier survival curves were constructed. Patient
      age, year of initial treatment, PNM stage, and risk factors were entered as co
      variates in a Cox regression modle that was used for analysis. RESULTS:
      Hepatectomy was performed in 144 patients diagnosed with hepatic AE (84 complete
      resections and 60 reduction surgeries). In the complete resection group, the 5-
      and 10-year OS rates were both 97.6%, and the 5- and 10-year PFS rates were both
      97.9%. In the reduction surgery group, the 5-, and 10-year OS rates were 89.7%
      and 73.4%, respectively, and the 5-, and 10-year PFS rates were 78.1% and 69.5%,
      respectively. Patients in the complete group had better OS prognoses and PFS than
      patients in the reduction surgery group (P = 0.018 and P = 0.001). Multivariate
      analysis indicated that curability and portal vein invasion are independent
      factors associated with PFS (P = 0.028 and P = 0.006). CONCLUSIONS: The most
      effective therapy for AE is complete resection. Reduction surgery does not appear
      to offer obvious advantages over benzimidazole therapy alone in the treatment of
      AE. Curability and portal vein invasion are independent prognostic factors for
      PFS in a multivariate analysis.

PMID- 27693515
TI  - How cellular membrane properties are affected by the actin cytoskeleton.
AB  - Lipid membranes define the boundaries of living cells and intracellular
      compartments. The dynamic remodelling of these membranes by the cytoskeleton, a
      very dynamic structure made of active biopolymers, is crucial in many biological
      processes such as motility or division. In this review, we present some aspects
      of cellular membranes and how they are affected by the presence of the actin
      cytoskeleton. We show that, in parallel with the direct study of membranes and
      cytoskeleton in vivo, biomimetic in vitro systems allow reconstitution of
      biological processes in a controlled environment. In particular, we show that
      liposomes, or giant unilamellar vesicles, encapsulating a reconstituted actin
      network polymerizing at their membrane are suitable models of living cells and
      can be used to decipher the relative contributions of membrane and actin on the
      mechanical properties of the cellular interface.

PMID- 27693516
TI  - Proteomic analysis of castor bean tick Ixodes ricinus: a focus on chemosensory
      organs.
AB  - In arthropods, the large majority of studies on olfaction have been focused on
      insects, where most of the proteins involved have been identified. In particular,
      chemosensing in insects relies on two families of membrane receptors,
      olfactory/gustatory receptors (ORs/GRs) and ionotropic receptors (IRs), and two
      classes of soluble proteins, odorant-binding proteins (OBPs) and chemosensory
      proteins (CSPs). In other arthropods, such as ticks and mites, only IRs have been
      identified, while genes encoding for OBPs and CSPs are absent. A third class of
      soluble proteins, called Niemann-Pick C2 (NPC2) has been suggested as potential
      carrier for semiochemicals both in insects and other arthropods. Here we report
      the results of a proteomic analysis on olfactory organs (Haller's organ and
      palps) and control tissues of the tick Ixodes ricinus, and of immunostaining
      experiments targeting NPC2s. Adopting different extraction and proteomic
      approaches, we identified a large number of proteins, and highlighted those
      differentially expressed. None of the 13 NPC2s known for this species was found.
      On the other hand, using immunocytochemistry, we detected reaction against one
      NPC2 in the Haller's organ and palp sensilla. We hypothesized that the low
      concentration of such proteins in the tick's tissues could possibly explain the
      discrepant results. In ligand-binding assays the corresponding recombinant NPC2
      showed good affinity to the fluorescent probe N-phenylnaphthylamine and to few
      organic compounds, supporting a putative role of NPC2s as odorant carriers.

PMID- 27693518
TI  - On the kinetics of chitosan/tripolyphosphate micro- and nanogel aggregation and
      their effects on particle polydispersity.
AB  - Submicron chitosan/tripolyphosphate (TPP) particles are widely investigated as
      nanocarriers for drugs, genes and vaccines. One of the key particle properties
      that requires control is their size distribution, which depends on the extent of
      chitosan/TPP primary nanoparticle aggregation into higher-order submicron
      colloids. To provide a better understanding of this higher-order aggregation
      process, this study analyzes the factors that control chitosan/TPP particle
      aggregation kinetics in the presence of free TPP (such as present during particle
      formation). The aggregation rates exhibit a sharp power-law decrease with the
      monovalent salt concentration and a power-law increase with the free TPP
      concentration. Moreover, the aggregation rates increase with the pH and with the
      chitosan degree of deacetylation (DD). These variations in aggregation rates
      reflect the effects of monovalent salt, TPP concentration, pH and chitosan DD on
      particle bridging by the surface-bound TPP. Furthermore, these aggregation rates
      are much faster than those predicted based on Derjaguin and Landau, Verwey and
      Overbeek (DLVO) interaction potentials, which might reflect nonuniformities in
      particle shape and charge, and/or complications caused by particle softness.
      Finally, implications of the above aggregation kinetics on the uniformity of
      chitosan/TPP micro- and nanogel size are analyzed, where we: (1) show how
      particle polydispersity can be diminished by lowering the chitosan DD; and (2)
      explain the opposing results on how chitosan/TPP particle polydispersity is
      affected by monovalent salt.

PMID- 27693517
TI  - Carbenoxolone exposure during late gestation in rats alters placental expressions
      of p53 and estrogen receptors.
AB  - Gestational carbenoxolone exposure inhibits placental 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD), the physiological barrier for glucocorticoids, which
      increases fetal exposure to glucocorticoids and induces intrauterine growth
      restriction (IUGR). We hypothesized that carbenoxolone exposure influences the
      expression of placental estrogen receptors-alpha and beta (ERalpha & ERbeta) and
      p53 leading to inhibited fetal and placental growth. Pregnant Sprague-Dawley rats
      were injected twice daily with either carbenoxolone (10mg/kg; s.c.) or vehicle
      (control group) from gestational days (dg) 12 onwards. Maternal blood and
      placentas were collected on 16 dg, 19 dg and 21 dg. The expression of ERalpha,
      ERbeta and p53 were studied in placental basal and labyrinth zones by RT-PCR,
      Western blotting and immunohistochemistry. Carbenoxolone did not affect placental
      and fetal body weights, but ELISA showed decreased estradiol levels on 19 dg and
      21 dg, and increased maternal luteinizing hormone levels on all dg. The follicle
      stimulating hormone levels decreased on 16 dg and 19 dg, and increased on 21 dg.
      Carbenoxolone decreased ERalpha mRNA levels on 16 dg in both zones and its
      protein level on 19 dg in the labyrinth zone. However, carbenoxolone increased
      ERbeta mRNA levels on 19 dg and 21 dg and protein levels on 16 dg and 19 dg in
      the labyrinth zone. The p53 mRNA levels increased on all dg, but its protein
      levels increased on 21 dg in both zones. In conclusion, carbenoxolone exposure
      changes placental p53, ERalpha, ERbeta expression in favor of cell death but
      these changes do not induce IUGR in rats.

PMID- 27693519
TI  - Conductive-probe measurements with nanodots of free-base and metallated
      porphyrins.
AB  - The conductive properties of nanodots of model porphyrins were investigated using
      conductive-probe atomic force microscopy (CP-AFM). Porphyrins provide excellent
      models for preparing surface structures that can potentially be used as building
      blocks for devices. The conjugated, planar structure of porphyrins offers
      opportunities for tailoring the electronic properties. Two model porphyrins were
      selected for studies, 5,10,15,20-tetraphenyl-21H,23H-porphine cobalt(II) (TPC)
      and its metal-free analog 5,10,15,20-tetraphenyl-21H,23H-porphine (TPP). Nanodots
      of TPP and TPC were prepared within a dodecanethiol resist on gold using particle
      lithography. The nanopatterned surfaces exhibit millions of reproducible test
      structures of porphyrin nanodots. The porphyrin nanodots have slight differences
      in dimensions at the nanoscale, to enable size-dependent measurements of
      conductive properties. The size of the nanodots corresponds to ~5-7 layers of
      porphyrin. The conductivity along the vertical direction of the nanodots was
      measured by applying a bias voltage between the gold surface and a metal-coated
      AFM cantilever. The TPP nanodots exhibited semi-conductive profiles while the TPC
      nanodots exhibited profiles that are typical of a conductive film or molecular
      wire. The engineered nanostructures of porphyrins provide an effective platform
      for investigation and measurement of conductive properties.

PMID- 27693520
TI  - Enhanced catalytic activity of CuPd alloy nanoparticles towards reduction of
      nitroaromatics and hexavalent chromium.
AB  - The present work reports a surfactant-free, economically feasible chemical route
      to synthesize bimetallic CuPd alloy nanoparticles under hydrothermal condition.
      The structural and morphological characterizations of the nanoparticles are
      carried out by XRD, SEM/EDX, TEM, XPS and BET surface area analyses. The
      synthetic strategy comprises of 9:1 molar composition of Cu2+ and Pd2+ salt in
      the aqueous solution. The size of the nanoparticles isca. 3-4nmwith very notable
      specific surface area of 298m2g-1. The synthesized nanoparticles exhibit
      excellent catalytic performance towards the aqueous phase reduction of 4
      nitrophenol and 4-nitroaniline in the presence of NaBH4 as a reducing agent.
      Furthermore the CuPd alloy nanoparticles also demonstrate remarkable activity
      towards reductive conversion of toxic Cr(VI) to less toxic Cr(III) at room
      temperature. Bimetallic CuPd alloy nanoparticles are catalytically more active
      and exhibit good recyclability in comparison to the monometallic Cu and Pd due to
      synergistic effect.

PMID- 27693521
TI  - Association Between Consumption of Red and Processed Meat and Pancreatic Cancer
      Risk: A Systematic Review and Meta-analysis.
AB  - BACKGROUND & AIMS: The relationship between consumption of red and processed meat
      and pancreatic cancer risk is inconclusive. We conducted a systematic review and
      meta-analysis to analyze this relationship. METHODS: We performed a systematic
      search of PubMed, EMBASE, and the Web of Science to identify studies that
      examined associations between consumption of different kinds of meat with
      pancreatic cancer and were published through February 2016. By using data from
      these articles, we associated level of consumption with cancer risk and performed
      subgroup, meta-regression, and publication bias analyses. RESULTS: We collected
      and analyzed data from a total of 28 studies that involved 3,143,777 participants
      (11,325 consumers of red meat) and 2,904,866 participants (9955 consumers of
      processed meat). We observed statistically significant differences between
      consumers and non-consumers of these meats in case-control studies (red meat, P =
      .02; processed meat, P < .01) but not in cohort studies (red meat, P = .09;
      processed meat, P = .18). In cohort studies, a 100 g/day increase in red meat
      consumption was associated with significant increase in risk of pancreatic cancer
      (P = .01); a 50 g/day increase in processed meat consumption was not associated
      with significant increase in risk of pancreatic cancer (P = .90). In cohort
      studies, we observed associations in consumption of red meat by men and
      pancreatic cancer (P < .01) and consumption of processed meat by men and
      pancreatic cancer (P < .01) but no associations for women (red meat, P = .61;
      processed meat, P = .88). CONCLUSIONS: In a systematic review and meta-analysis,
      we found case-control but not cohort studies to associate consumption of red and
      processed meat with risk of pancreatic cancer. However, in cohort studies,
      consumption of red and processed meat appeared to increase risk of pancreatic
      cancer in men but not in women.

PMID- 27693522
TI  - Early Experience With Endoscopic Sleeve Gastroplasty and Hints at Mechanisms of
      Action.

PMID- 27693523
TI  - Is the Risk of Death Enhanced in Immunosuppressed Hepatitis B Virus-infected
      Patients Who Develop Acute Liver Failure?

PMID- 27693524
TI  - Endoscopic Ultrasonography-Guided Gastrojejunostomies With Lumen-Apposing Metal
      Stents.

PMID- 27693525
TI  - A stage structured mosquito model incorporating effects of precipitation and
      daily temperature fluctuations.
AB  - An outbreak of dengue fever in Guangdong province in 2014 was the most serious
      outbreak ever recorded in China. Given the known positive correlation between the
      abundance of mosquitoes and the number of dengue fever cases, a stage structured
      mosquito model was developed to investigate the cause of the large abundance of
      mosquitoes in 2014 and its implications for outbreaks of the disease. Data on the
      Breteau index (number of containers positive for larvae per 100 premises
      investigated), temperature and precipitation were used for model fitting. The egg
      laying rate, the development rate and the mortality rates of immatures and adults
      were obtained from the estimated parameters. Moreover, effects of daily
      fluctuations of temperature on these parameters were obtained and the effects of
      temperature and precipitation were analyzed by simulations. Our results indicated
      that the abundance of mosquitoes depended not only on the total annual
      precipitation but also on the distribution of the precipitation. The daily mean
      temperature had a nonlinear relationship with the abundance of mosquitoes, and
      large diurnal temperature differences can reduce the abundance of mosquitoes. In
      addition, effects of increasing precipitation and temperature were
      interdependent. Our findings suggest that the large abundance of mosquitoes in
      2014 was mainly caused by the distribution of the precipitation. In the
      perspective of mosquito control, our results reveal that it is better to clear
      water early and spray insecticide between April and August in case of limited
      resources.

PMID- 27693526
TI  - A phylogenetic test of sympatric speciation in the Hydrobatinae (Aves:
      Procellariiformes).
AB  - Phylogenetic relationships among species can provide insight into how new species
      arise. For example, careful consideration of both the phylogenetic and geographic
      distributions of species in a group can reveal the geographic models of
      speciation within the group. One such model, sympatric speciation, may be more
      common than previously thought. The Hydrobatinae (Aves: Procellariformes) is a
      diverse subfamily of Northern Hemisphere storm-petrels for which the taxonomy is
      unclear. Previous studies showed that Hydrobates (formally Oceanodroma) castro
      breeding in the Azores during the cool season is sister species to H. monteiroi,
      a hot season breeder at the same locations, which suggests sympatric speciation
      by allochrony. To test whether other species within the subfamily arose via
      sympatric speciation by allochrony, we sequenced the cytochrome b gene and five
      nuclear introns to estimate a phylogenetic tree using multispecies coalescent
      methods, and to test whether species breeding in the same geographic area are
      monophyletic. We found that speciation within the Hydrobatinae appears to have
      followed several geographic modes of divergence. Sympatric seasonal species in
      Japan likely did not arise through sympatric speciation, but allochrony may have
      played a role in the divergence of H. matsudairae, a cool season breeder, and H.
      monorhis, a hot season breeder. No other potential cases of sympatric speciation
      were discovered within the subfamily. Despite breeding in the same geographic
      area, hydrobatine storm-petrels breeding in Baja California (H. microsoma and H.
      melania) are each sister to a species breeding off the coast of Peru (H. tethys
      and H. markhami, respectively). In fact, antitropical sister species appear to
      have diverged at multiple times, suggesting allochronic divergence might be
      common. In addition, allopatry has likely played a role in divergence of H.
      furcata, a north Pacific breeder, and H. pelagius, a north Atlantic breeder. This
      study demonstrates that a variety of mechanisms of divergence have played a role
      in generating the diversity of the Hydrobatinae and supports the current taxonomy
      of the subfamily.

PMID- 27693527
TI  - Effect of HFD/STZ on expression of genes involved in lipid, cholesterol and
      glucose metabolism in rats.
AB  - AIMS: The aim of the study was to evaluate lipid, cholesterol and glucose
      metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD).
      MAIN METHODS: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single
      low dose (35mg/kg) of streptozotocin (STZ). Collagen and glycogen content,
      oxidative stress and glucokinase activity were measured using biochemical assays.
      Other metabolic pathways were assessed by qRT-PCR. KEY FINDINGS: HFD/STZ treated
      rats, compared to control ones, showed an increase in expression of biomarkers of
      inflammation (TNFalpha, IL6), fibrosis (TGFbeta), mitochondrial stress (UCP2) and
      oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP,
      XBP1). Additionally, HFD/STZ treatment caused a reduction in glycogen content,
      glucokinase activity (a limiting step in glycolysis) and expression of ChREBP
      gene (a de novo lipogenesis regulator), suggesting a modified glycolytic pathway.
      The cholesterol biosynthesis in HFD/STZ treated rats was inhibited (reduced
      expression of SREBP-2-regulated HMGCoA red and LDLr), instead the cholesterol
      catabolism was increased, as shown by the mRNA induction of the CYP7A1 and CYP8B1
      (key genes for BA acid). A reduced gene expression of FXR-dependent SHP (a key
      gene for feedback inhibition of CYP7A1 and CYP8B1) and of bile acids (NTCP,
      OATP1A1, BSEP) and cholesterol (ABCA1) transporters was found. SIGNIFICANCE:
      These results widely extend the characterization of HFD/STZ rat model, which
      might mimic the NAFLD/NASH in diabetic humans.

PMID- 27693528
TI  - Inequality dynamics in the workplace among microbiologists and infectious disease
      specialists: a qualitative study in five European countries.
AB  - OBJECTIVE: To explore the social, cultural, psychological and organizational
      factors associated with inequality in the workplace among clinical
      microbiologists (CM) and infectious disease (ID) specialists in European
      hospitals. METHODS: We analysed data from 52 interviews and five focus groups
      involving 82 CM/ID specialists selected from university, research or community
      hospitals in five countries, one each in Northern, Western, Eastern, Southeastern
      and Southwestern Europe. The 80 hours of recordings were transcribed, and the
      anonymous database coding process was cross-checked iteratively by six
      researchers. RESULTS: Inequality affects all the institutions in all the
      countries we looked at, denying or reducing access to professional assets with
      intensity and form that vary largely according to the cultural and organizational
      context. Discrimination is generally not explicit and uses disrespectful
      microbehaviours that are hard to respond to when they occur. Inequality affected
      also loans, distribution of research funds and gender and country representation
      in boards and conference faculty. Parenthood has a major impact on women's
      careers, as women are still mainly responsible for family care. Responses to
      discrimination range from reactive to surrender strategies. CONCLUSIONS: Our
      study offers an effective model for diagnosing discriminatory behaviours in a
      medical professional setting. Knowledge of inequality's drivers could help
      national ID/CM societies in collaboration with major European stakeholders to
      further reduce such discrimination. The effect of discrimination on the quality
      of healthcare in Europe needs further exploration.

PMID- 27693529
TI  - Use of whole genome sequencing in the Dutch Acute HCV in HIV study: focus on
      transmitted antiviral resistance.
AB  - OBJECTIVE: Within HIV-positive men having sex with men, the epidemic of hepatitis
      C virus (HCV) is ongoing. Transmission of resistant variants of HCV after failure
      of treatment with directly acting antivirals (DAA) could be a major threat to the
      effectivity of therapy. We determined whether HCV-resistant variants to DAAs were
      prevalent amongst patients with an acute HCV infection diagnosed in 2013 and 2014
      in the Netherlands. METHODS: Target enrichment for viral nucleic acid separation
      and deep sequencing were used to recover whole HCV genomes of 50 patients with an
      acute HCV infection. The genomes were assembled by de novo assembly and analysed
      for known DAA resistance mutations. RESULTS: In acute HCV infected treatment
      naive patients, the relevant resistance-associated substitutions were Q80K (40%)
      in NS3/4a, M28V (24%) and Q30H combined with Y93H (2%) in NS5A and M414T (2%) or
      S556G (2%) in NS5b. Patients whose HCV infection failed to respond to boceprevir,
      peginterferon and ribavirin therapy developed mutations in NS3 at position T54A
      and R155K. CONCLUSIONS: Target enrichment and whole genome sequencing were
      successfully applied directly on clinical samples from patients with an acute HCV
      infection.

PMID- 27693530
TI  - Plasma concentration of fibronectin is decreased in patients with hypertrophic
      cardiomyopathy.
AB  - OBJECTIVES: To confirm the initial iTRAQ-based proteomic findings related to the
      plasma fibronectin level and hypertrophic cardiomyopathy using an antibody-based
      assay. METHODS: The iTRAQ technique was used for the discovery proteomic analysis
      of the pooled plasma samples. The ELISA was used for verification of fibronectin
      plasma concentration in individual samples. Additional five related plasma
      proteins were assessed: matrix metalloproteinase 2, matrix metalloproteinase 9,
      tissue inhibitor of metalloproteinase 1, tissue inhibitor of metalloproteinase 2
      and brain natriuretic peptide. RESULTS: The plasma fibronectin level in patients
      with hypertrophic cardiomyopathy was significantly lower in comparison to the
      healthy subjects [215.5+/-47.3MUg/ml, n=17 vs. 376.7+/-134.8MUg/ml, n=17;
      p<0.0001]. CONCLUSION: In this study we present and confirm our initial proteomic
      findings and we suggest fibronectin as a potential indicator of an extracellular
      matrix remodeling related to the hypertrophic cardiomyopathy.

PMID- 27693531
TI  - Simultaneous screening for JAK2 and calreticulin gene mutations in
      myeloproliferative neoplasms with high resolution melting.
AB  - INTRODUCTION: Recently, novel calreticulin (CALR) mutations were discovered in
      Janus kinase 2 (JAK2) non-mutated myelofibrosis (PMF) and essential
      thrombocythemia (ET) cases, with a frequency of 60-80%. We examined clinical
      correlations and CALR mutation frequency in our myeloproliferative neoplasms
      (MPN) cases, and introduce an effective test method for use in clinical practice.
      METHODS: We examined 177 samples previously investigated for the JAK2 mutation
      for differential diagnosis of MPN. JAK2 and CALR mutations were analyzed using
      melting curve analysis and microchip electrophoresis, respectively. Next, we
      constructed a test for simultaneous screening of the JAK2 and CALR mutations
      utilizing high resolution melting (HRM). RESULTS: Among 99 MPN cases, 60
      possessed the JAK2 mutation alone. Of the 39 MPN cases without the JAK2 mutation,
      14 were positive for the CALR mutation, all of which were ET. Using our novel
      screening test for the JAK2 and CALR mutations by HRM, the concordance rate of
      conventional analysis with HRM was 96% for the JAK2 mutation and 95% for the CALR
      mutation. CONCLUSION: Our novel simultaneous screening test for the JAK2 and CALR
      gene mutations with HRM is useful for diagnosis of MPN.

PMID- 27693532
TI  - Sex differences on the competitive place task in the water maze: The influence of
      peripheral pool time on spatial navigation performance in rats.
AB  - This study investigated sex differences on the competitive place version of the
      Morris water maze task to determine whether potential strategy differences would
      emerge during any phase of the study but in particular on the competitive place
      phase. Previous findings indicate that this version of the task is highly
      sensitive to measures that disrupt NMDA-dependent synaptic plasticity within the
      hippocampus during memory consolidation (McDonald et al., 2005). The present
      findings revealed significant sex differences during all phases of the study,
      including Phase I with standard place training to located a hidden platform/goal,
      Phase II mass training to a new place with the platform/goal relocated to the
      diagonally opposite quadrant and Phase III, competitive place probe test with the
      platform removed to measure spatial behaviour directed at either location. The
      findings showed no sex difference in escape latency and other standard
      performance measures during the first two phases, initial place acquisition and
      mass training to a new location. A very subtle male advantage in visiting both
      Old and New place locations during the third phase place competition test was
      observed, however, in the time spent swimming in the periphery of the pool, the
      pool wall (Zone C - outer third radial distance) was increased for females during
      all phases of the study, suggesting a general effect may have influenced place
      location search behaviour of the females. Increased peripheral pool time may
      represent a female preference for approaching the wall, a local cue.
      Alternatively, the possibility that increased peripheral swimming/thigmotaxis may
      represent hormonal influences interacting with strategic preferences were
      discussed, though no definitive conclusions about sex differences in cognitive
      spatial performance or memory consolidation were inferred from the present
      findings. The findings suggest that mixed results reported in the literature by
      others may be due in part to an interaction with a persistent peripheral pool
      swimming response demonstrated in female rats.

PMID- 27693533
TI  - Coding and quantification of a facial expression for pain in lambs.
AB  - Facial expressions are routinely used to assess pain in humans, particularly
      those who are non-verbal. Recently, there has been an interest in developing
      coding systems for facial grimacing in non-human animals, such as rodents,
      rabbits, horses and sheep. The aims of this preliminary study were to: 1.
      Qualitatively identify facial feature changes in lambs experiencing pain as a
      result of tail-docking and compile these changes to create a Lamb Grimace Scale
      (LGS); 2. Determine whether human observers can use the LGS to differentiate tail
      docked lambs from control lambs and differentiate lambs before and after docking;
      3. Determine whether changes in facial action units of the LGS can be objectively
      quantified in lambs before and after docking; 4. Evaluate effects of restraint of
      lambs on observers' perceptions of pain using the LGS and on quantitative
      measures of facial action units. By comparing images of lambs before (no pain)
      and after (pain) tail-docking, the LGS was devised in consultation with
      scientists experienced in assessing facial expression in other species. The LGS
      consists of five facial action units: Orbital Tightening, Mouth Features, Nose
      Features, Cheek Flattening and Ear Posture. The aims of the study were addressed
      in two experiments. In Experiment I, still images of the faces of restrained
      lambs were taken from video footage before and after tail-docking (n=4) or sham
      tail-docking (n=3). These images were scored by a group of five naive human
      observers using the LGS. Because lambs were restrained for the duration of the
      experiment, Ear Posture was not scored. The scores for the images were averaged
      to provide one value per feature per period and then scores for the four LGS
      action units were averaged to give one LGS score per lamb per period. In
      Experiment II, still images of the faces nine lambs were taken before and after
      tail-docking. Stills were taken when lambs were restrained and unrestrained in
      each period. A different group of five human observers scored the images from
      Experiment II. Changes in facial action units were also quantified objectively by
      a researcher using image measurement software. In both experiments LGS scores
      were analyzed using a linear MIXED model to evaluate the effects of tail docking
      on observers' perception of facial expression changes. Kendall's Index of
      Concordance was used to measure reliability among observers. In Experiment I,
      human observers were able to use the LGS to differentiate docked lambs from
      control lambs. LGS scores significantly increased from before to after treatment
      in docked lambs but not control lambs. In Experiment II there was a significant
      increase in LGS scores after docking. This was coupled with changes in other
      validated indicators of pain after docking in the form of pain-related behaviour.
      Only two components, Mouth Features and Orbital Tightening, showed significant
      quantitative changes after docking. The direction of these changes agree with the
      description of these facial action units in the LGS. Restraint affected people's
      perceptions of pain as well as quantitative measures of LGS components. Freely
      moving lambs were scored lower using the LGS over both periods and had a
      significantly smaller eye aperture and smaller nose and ear angles than when they
      were held. Agreement among observers for LGS scores were fair overall (Experiment
      I: W=0.60; Experiment II: W=0.66). This preliminary study demonstrates changes in
      lamb facial expression associated with pain. The results of these experiments
      should be interpreted with caution due to low lamb numbers.

PMID- 27693534
TI  - Age and egg-sac loss determine maternal behaviour and locomotor activity of wolf
      spiders (Araneae, Lycosidae).
AB  - Wolf spiders' (Lycosidae) maternal behaviour includes a specific phase called
      "egg brooding" which consists of guarding and carrying an egg-sac throughout the
      incubation period. The transport of an egg-sac can restrict mothers' exploratory
      and locomotor activity, in particular when foraging. The present study details
      the ontogeny of maternal behaviour and assesses the influence of age of egg-sac
      (or embryos' developmental stage) on vagrant wolf spider Pardosa saltans females'
      exploration and locomotion. We observed these spiders' maternal behaviour in the
      laboratory and evaluated their locomotor activity using a digital activity
      recording device. Our subjects were virgin females (without egg-sac) and first
      time mothers (with her egg-sac) who were divided into three groups. The first
      group of mothers were tested on the day the egg-sac was built (day 0), and the
      females of the other two groups were tested 10 or 15days after they had built
      their egg-sac. We evaluated the effects of the presence and the loss of egg-sac
      on mothers' activity. Pardosa saltans females' behaviour depended on mothers'
      physiological state and/or age of egg-sac (developmental stage of embryos).
      Virgin females' behaviour was not modified by the presence of an egg-sac in their
      environment. Mothers' reactions to the presence, the loss and the recovery of
      their egg-sac varied during the maternal cycle. Maternal behaviour changed with
      age of egg-sac, but the levels of locomotor activity of mothers with egg-sacs was
      similar to those of virgin females. Loss of egg-sac modified the maternal
      behaviour and locomotor activity of all mothers; these modifications were greater
      on "day 15" when embryos had emerged from eggs. All mothers were able to retrieve
      their egg-sacs and to re-attach them to their spinnerets.

PMID- 27693535
TI  - Intracranial Activity of Cabozantinib in MET Exon 14-Positive NSCLC with Brain
      Metastases.
AB  - INTRODUCTION: A significant portion of NSCLCs with MET proto-oncogene, receptor
      tyrosine kinase gene (MET) exon 14 skipping alterations are sensitive to small
      molecule mesenchymal-epithelial transition tyrosine kinase inhibitors. However,
      the incidence and management of brain metastases in this molecular subset is
      unknown and represents an unmet clinical need. METHODS: Hybrid capture-based
      comprehensive genomic profiling identified a patient with a MET exon 14 skipping
      alteration, and serial magnetic resonance imaging was utilized to follow
      intracranial disease during crizotinib and subsequent cabozantinib therapy.
      RESULTS: Intracranial progression developed in the context of ongoing
      extracranial disease control during crizotinib therapy. Rapid intracranial
      response was observed after change to cabozantinib. CONCLUSIONS: This report
      provides the first detailed description of brain metastases in MET exon 14
      positive NSCLC and provides preliminary support for the intracranial activity of
      cabozantinib. Prospective study is warranted and needed to refine the management
      of intracranial disease in MET exon 14-positive NSCLC.

PMID- 27693537
TI  - Resveratrol treatment attenuates chemokine receptor expression in the BTBR T+tf/J
      mouse model of autism.
AB  - Autism is a neurodevelopmental disorder categorized by qualitative impairments in
      social interaction, communication, and repetitive stereotypic behavior. Emerging
      evidence increasingly suggests that chemokine receptors have a pivotal role in
      the central nervous system and are involved in the pathogenesis of numerous
      neuroinflammatory diseases. Resveratrol is widely used to treat neurodegenerative
      diseases, but its effect on autism has not been investigated. We investigated the
      effect of resveratrol (20 and 40mg/kg) in the spleen and brain tissues of BTBR
      T+tf/J (BTBR) and C57BL/6J (B6) mice as well as on the C-C chemokine receptor
      (CCR) and C-X-C motif chemokine receptor (CXCR) (CCR3+, CCR5+, CCR7+ and CCR9+,
      CXCR3+ and CXCR5+) in cluster of differentiation 4-positive (CD4+) T cells in the
      spleen. We also assessed the mRNA expression of CCR and CXCR receptors in the
      spleen and brain tissues. Our study revealed that the BTBR and B6 control mice
      showed different immune profiles. The BTBR mice showed characteristic higher
      levels of both CCR and CXCR production and expression in CD4+ T cells than the B6
      control mice did. Treatment of B6 and BTBR mice with resveratrol (20 and 40mg/kg)
      induced a substantial decrease in the CCR and CXCR production and expression in
      CD4+ T cells compared with the respective untreated control groups. Moreover,
      resveratrol treatment decreased the mRNA expression levels of CCR and CXCR in the
      spleen and brain tissues. Resveratrol downregulated the chemokine receptor
      levels, which might provide unique targets for future therapies for autism.

PMID- 27693536
TI  - Research for new drugs for elimination of onchocerciasis in Africa.
AB  - Onchocerciasis is a parasitic, vector borne disease caused by the filarial
      nematode Onchocerca volvulus. More than 99% of the population at risk of
      infection live in Africa. Onchocerciasis control was initiated in West Africa in
      1974 with vector control, later complemented by ivermectin mass drug
      administration and in the other African endemic countries in 1995 with annual
      community directed treatment with ivermectin (CDTI.) This has significantly
      reduced infection prevalence. Together with proof-of-concept for onchocerciasis
      elimination with annual CDTI from foci in Senegal and Mali, this has resulted in
      targeting onchocerciasis elimination in selected African countries by 2020 and in
      80% of African countries by 2025. The challenges for meeting these targets
      include the number of endemic countries where conflict has delayed or interrupted
      control programmes, cross-border foci, potential emergence of parasite strains
      with low susceptibility to ivermectin and co-endemicity of loiasis, another
      parasitic vector borne disease, which slows down or prohibits CDTI
      implementation. Some of these challenges could be addressed with new drugs or
      drug combinations with a higher effect on Onchocerca volvulus than ivermectin.
      This paper reviews the path from discovery of new compounds to their
      qualification for large scale use and the support regulatory authorities provide
      for development of drugs for neglected tropical diseases. The status of research
      for new drugs or treatment regimens for onchocerciasis along the path to
      regulatory approval and qualification for large scale use is reviewed. This
      research includes new regimens and combinations of ivermectin and albendazole,
      antibiotics targeting the O. volvulus endosymbiont Wolbachia, flubendazole,
      moxidectin and emodepside and discovery of new compounds.

PMID- 27693538
TI  - Gene expression profiling of bovine ovarian follicular and luteal cells provides
      insight into cellular identities and functions.
AB  - After ovulation, somatic cells of the ovarian follicle (theca and granulosa
      cells) become the small and large luteal cells of the corpus luteum. Aside from
      known cell type-specific receptors and steroidogenic enzymes, little is known
      about the differences in the gene expression profiles of these four cell types.
      Analysis of the RNA present in each bovine cell type using Affymetrix microarrays
      yielded new cell-specific genetic markers, functional insight into the behavior
      of each cell type via Gene Ontology Annotations and Ingenuity Pathway Analysis,
      and evidence of small and large luteal cell lineages using Principle Component
      Analysis. Enriched expression of select genes for each cell type was validated by
      qPCR. This expression analysis offers insight into cell-specific behaviors and
      the differentiation process that transforms somatic follicular cells into luteal
      cells.

PMID- 27693539
TI  - Hepatocellular carcinoma in the absence of cirrhosis in patients with chronic
      hepatitis B virus infection.
AB  - BACKGROUND & AIMS: Cirrhosis related to chronic hepatitis B (CHB) is a major risk
      factor for hepatocellular carcinoma (HCC). The extent to which HCC occurs in U.S.
      in the absence of cirrhosis in CHB remains unclear. METHODS: We identified CHB
      patients who were diagnosed with HCC in the national Veterans Administration (VA)
      between 2001 and 2013. We defined presence and absence of cirrhosis at the time
      of HCC diagnosis using explicit histological, radiological, endoscopic, and
      laboratory criteria. We used multivariable regression analysis to identify
      demographic and clinical characteristics associated with CHB-related HCC in the
      absence of cirrhosis. We also examined liver transplant-free survival in CHB-HCC
      patients with and without cirrhosis. RESULTS: Among 8539 CHB patients, 317
      developed HCC of whom 30 (9.5%) did not have any evidence of cirrhosis at the
      time of HCC diagnosis. Compared to HCC patients with cirrhosis, HCC patients
      without cirrhosis were more likely to be non-white (African American, OR=6.78;
      95% CI 2.05-22.4; Asian, OR 11.6, 95% CI 2.63-50.8), have a family history of HCC
      (OR 32.9, 95% CI 3.76-288), and hypertension (OR 3.15, 95% CI 1.02-9.75). There
      was no significant difference in the transplant-free survival between CHB-HCC
      patients with and without cirrhosis (hazard ratio 0.68, 95% CI 0.43-1.09).
      CONCLUSIONS: Fewer than 10% of U.S. based CHB-related HCC patients did not have
      cirrhosis. Race and family history of HCC were the main risk factors for HCC in
      the absence of cirrhosis in CHB. These factors may help guide the decision to
      initiate HCC surveillance in CHB patients without cirrhosis. LAY SUMMARY:
      Patients with chronic hepatitis B who are African American, or Asian, older than
      40years of age with family members with liver cancer or high blood pressure are
      at a higher risk of developing liver cancer in the absence of cirrhosis. These
      patients should be included in the screening program for liver cancer.

PMID- 27693540
TI  - Characterization and signaling pathway analysis of interferon-kappa in bovine.
AB  - A bovine interferon-kappa (BoIFN-kappa) gene was amplified, which encodes a
      protein of 215 amino acids sharing 63% identity with human IFN-kappa. BoIFN-kappa
      was demonstrated to have antiviral and antiproliferative activities. Moreover,
      BoIFN-kappa was shown to be highly sensitive to trypsin, however, it remained
      stable despite changes in pH and temperature. Result showed that BoIFN-kappa can
      bind with bovine type I IFN receptors, and the antiviral activity can be blocked
      by antibodies against type I IFN receptors or BoIFN-kappa. Additionally, BoIFN
      kappa can induce the transcription of Mx1, ISG15 and ISG56 gene, as well as the
      expression of Mx1 protein. The NF-kappaB, ISRE, and BoIFN-beta promoter can all
      be activated by BoIFN-kappa. This study revealed that BoIFN-kappa exhibits the
      typical characteristics of type I IFNs and exerts antiviral activity via
      activation of the JAK-STAT signaling pathway. Overall, these findings will enrich
      the current knowledge about IFN-kappa and facilitate further research on the role
      of type I IFN in antiviral defense responses in bovine.

PMID- 27693542
TI  - The role of Fusobacterium necrophorum in pharyngotonsillitis - A review.
AB  - Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the
      causative agent of the invasive disease Lemierre's syndrome. In addition, it is
      also associated with peritonsillar abscess formation and otitis media in small
      children. Recent research has shown that F. necrophorum may be involved in
      pharyngotonsillitis especially in adolescent and young adults and that it may be
      the second most common bacterial cause of pharyngotonsillitis after Streptococcus
      pyogenes (Group A streptococci). Peritonsillar abscesses and Lemierre's syndrome
      due to F. necrophorum are also found in this age group, suggesting that they may
      be complications of F. necrophorum pharyngotonsillitis. In this review we present
      the present knowledge about the role of F. necrophorum in pharyngotonsillitis
      with special emphasis on the age distribution. We argue that F. necrophorum is an
      important pathogen involved in pharyngotonsillitis in the age group of 13-40
      years of age and we urge clinical microbiology labs to set up the appropriate
      techniques to be able to detect F. necrophorum from throat swabs.

PMID- 27693541
TI  - Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and
      Lung Cancer-Specific Death in Squamous Cell Carcinoma.
AB  - INTRODUCTION: Spread through air spaces (STAS) is a recently recognized pattern
      of invasion in lung adenocarcinoma; however, it has not yet been characterized in
      squamous cell carcinoma (SCC). METHODS: We reviewed 445 resected stage I to III
      lung SCCs and investigated the clinical significance of STAS. Cumulative
      incidence of recurrence and lung cancer-specific death were evaluated by
      competing risks analyses and overall survival by Cox models. RESULTS: Of the
      total 445 patients, 336 (76%) were older than 65 years. Among the 273 patients
      who died, 91 (33%) died of lung cancer whereas the remaining ones died of
      competing events or unknown cause. STAS was observed in 132 patients (30%) and
      the frequency increased with stage. The cumulative incidences of any, distant,
      and locoregional recurrence as well as lung cancer-specific death were
      significantly higher in patients with STAS compared with in those without STAS,
      whereas there was no statistically significant difference in overall survival. In
      multivariable models for any recurrence and lung cancer-specific death, STAS was
      an independent predictor for both outcomes (p = 0.034 and 0.016, respectively).
      CONCLUSION: STAS was present in one-third of resected lung SCCs. In competing
      risks analysis in a cohort in which three-fourths of the patients were elderly,
      STAS was associated with lung cancer-specific outcomes. Our findings suggest that
      STAS is one of the most prognostically significant histologic findings in lung
      SCC.

PMID- 27693543
TI  - Clostridium difficile: A rare cause of pyogenic liver abscess.
AB  - Extra-intestinal infections due to Clostridium difficile have been reported
      rarely. Herein we report a case of pyogenic liver abscess from toxigenic C.
      difficile in an 80-year-old non-hospitalized woman with diabetes mellitus,
      cerebrovascular and cardiovascular diseases. The patient was admitted to the
      emergency department with fever and abdominal pain. There was no history of
      diarrhea or use of antibiotics. Laboratory parameters revealed signs of
      inflammation and elevated AST and ALT levels. Abdominal ultrasound and computer
      tomography showed multiple focal lesions in the bilateral liver lobes and
      hydropic gallbladder with stones. The patient underwent cholecystectomy and the
      liver abscesses were drained. Toxigenic C. difficile strains were isolated from
      the drained pus and also from the stool sample. According to repetitive-element
      PCR (rep-PCR) analyses both organisms were the same. The organisms were
      susceptible to antibiotics. Despite proper antibiotic therapy and surgical
      drainage, the patient succumbed to her illness.

PMID- 27693544
TI  - Bypass graft infection and bacteremia caused by Anaerostipes caccae: First report
      of human infection caused by a recently described gut anaerobe.
AB  - We report a case of bypass graft infection and bacteremia caused by Anaerostipes
      caccae. A review of the literature shows no reported human infection caused by
      this microorganism to date. The patient was initially treated with vancomycin and
      piperacillin-tazobactam on admission and with amoxicillin-clavulanate upon
      discharge. The slow-growing organism was subsequently found to be susceptible to
      metronidazole and ertapenem.

PMID- 27693545
TI  - Controlled bone formation using ultrasound-triggered release of BMP-2 from
      liposomes.
AB  - Recombinant human bone morphogenetic protein 2 (rhBMP-2) is used clinically to
      enhance implant-mediated bone regeneration. However, there are risks associated
      with the high rhBMP-2 dose that is required in the implant to mitigate
      diffusional loss over the therapeutic timespan. On-demand, localized control over
      delivery of rhBMP-2, days after implantation, would therefore be an attractive
      solution in the area of bone repair and reconstruction, yet this has posed a
      significant challenge, with little data to support in vivo efficacy to date. To
      address this, we have developed novel liposome-rhBMP-2 nanocomplexes that release
      rhBMP-2 in response to non-thermogenic, clinical diagnostic ultrasound exposure.
      In vitro validation shows that rhBMP-2 release is in proportion to applied
      ultrasound pressure and duration of exposure. Moreover, here we show in vivo
      validation of this ultrasound-triggered rhBMP-2 delivery system in a standard
      mouse bone regeneration model. Implanted into hindleg muscles, the liposome-rhBMP
      2 nanocomplexes induced local bone formation only after ultrasound exposure. Such
      post-implantation control of delivery has potential to improve the safety,
      efficacy and cost of rhBMP-2 use in bone reconstruction. Furthermore, this first
      proof-of-concept demonstration of in vivo efficacy for ultrasound-triggered
      liposomal delivery of rhBMP-2 has broader implications for tunable delivery of a
      variety of drugs and biologics in medicine and tissue engineering.

PMID- 27693546
TI  - An acute, non-therapeutic dose of methylphenidate disrupts partner preference in
      female rats.
AB  - The present study was designed to test the effects of an acute, high dose of
      methylphenidate (MPH; trademarked as Ritalin) on sexual behavior in female Long
      Evans rats. In Experiment 1, naturally cycling subjects in estrus were tested for
      partner preference 20min after receiving an i.p. injection of MPH 10mg/kg (n=8)
      or saline (n=7). During the partner-preference test, female subjects were given
      the choice to interact with a sexually active male stimulus or a sexually
      receptive female stimulus. Physical contact was limited by placing the stimulus
      animals behind a wire mesh during the no-contact phase of the test, whereas
      physical contact was not limited during the contact phase. Female subjects that
      received MPH spent significantly less time with the male stimulus than the saline
      treated subjects during both phases (no-contact and contact) of the partner
      preference test. This acute dose of MPH did not affect visits to the female
      stimulus; however, MPH-treated subjects made fewer visits to the male stimulus
      than the saline-treated subjects during the contact phase of the partner
      preference test. Consistent with previous findings, MPH increased line crossings
      when subjects were tested in an open field immediately after the partner
      preference test. In Experiment 2, female subjects were ovariectomized (OVX),
      primed with estradiol benzoate and progesterone, and tested for partner
      preference 20min after receiving an injection of MPH 10mg/kg (n=8) or saline
      (n=8). Similar to the results of Experiment 1, OVX hormone-primed subjects that
      received MPH spent significantly less time with the male stimulus than the saline
      treated subjects during both phases of the partner-preference test. Although MPH
      treated subjects were sexually receptive, they displayed fewer proceptive
      behaviors (i.e., hops and darts) than saline-treated subjects. Two-weeks later,
      the subjects from Experiment 2 were tested in an open field 20min after receiving
      an injection of MPH 10mg/kg or saline (counterbalancing previous MPH exposure).
      Once again MPH increased locomotor activity. In conclusion, the effects of MPH
      were equally as robust in naturally cycling subjects as in the more commonly used
      OVX-hormone primed subjects. The results of the present study suggest that an
      acute, non-therapeutic dose of MPH disrupts approach and interest in a male
      stimulus during a test of partner preference. This avoidance of the male stimulus
      may be the result of a decrease in the incentive value of a sexual partner.

PMID- 27693547
TI  - Meditation and auditory attention: An ERP study of meditators and non-meditators.
AB  - The findings of a study by Cahn and Polich (2009) suggests that there is an
      effect of a meditative state on three event-related potential (ERP) brain markers
      of "low-level" auditory attention (i.e., acoustic representations in sensory
      memory) in expert meditators: the N1, the P2, and the P3a. The current study
      built on these findings by examining trait and state effects of meditation on the
      passive auditory mismatch negativity (MMN), N1, and P2 ERPs. We found that the
      MMN was significantly larger in meditators than non-meditators regardless of
      whether they were meditating or not (a trait effect), and that N1 amplitude was
      significantly attenuated during meditation in non-meditators but not expert
      meditators (an interaction between trait and state). These outcomes suggest that
      low-level attention is superior in long-term meditators in general. In contrast,
      low-level attention is reduced in non-meditators when they are asked to meditate
      for the first time, possibly due to auditory fatigue or cognitive overload.

PMID- 27693550
TI  - Fabrication of layered (CdS-Mn/MoS2/CdTe)-promoted TiO2 nanotube arrays with
      superior photocatalytic properties.
AB  - A novel (CdS-Mn/MoS2/CdTe)-sensitized TiO2 nanotube arrays (NTAs) photoelectrode
      has been prepared by electrodeposite, successive ionic layer adsorption and
      reaction (SILAR) coupled with hydrothermal method. When a ZnS layer was added on
      the top of CdS-Mn/MoS2/CdTe/TiO2, a notable red-shift and high absorption was
      observed in the visible light region. The photocurrent density (mA/cm2)
      systematically increases from TiO2 NTAs (0.43), CdTe/TiO2 (1.09), MoS2/CdTe/TiO2
      (1.80), CdS-Mn/MoS2/CdTe/TiO2 (2.40), to ZnS/CdS-Mn/MoS2/CdTe/TiO2 (3.41) under
      visible light irradiation, due to the type-II semiconductor heterostructures
      comprising multiple components with a staggered band offset. Such a
      heterostructure possesses an enhanced photocatalytic performance towards
      degradation of organic contaminant, e.g. P-Nitrophenol (PNP) and Rhodamine B
      (RhB).

PMID- 27693549
TI  - Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and
      motor impairment in a mouse model of Parkinson's disease.
AB  - Neuroinflammation involves the activation of glial cells, which is associated to
      the progression of neurodegeneration in Parkinson's disease. Recently, we and
      other researchers demonstrated that dopamine receptor D3 (D3R)-deficient mice are
      completely refractory to neuroinflammation and consequent neurodegeneration
      associated to the acute intoxication with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). In this study we examined the therapeutic potential
      and underlying mechanism of a D3R-selective antagonist, PG01037, in mice
      intoxicated with a chronic regime of administration of MPTP and probenecid
      (MPTPp). Biodistribution analysis indicated that intraperitoneally administered
      PG01037 crosses the blood-brain barrier and reaches the highest concentration in
      the brain 40 min after the injection. Furthermore, the drug was preferentially
      distributed to the brain in comparison to the plasma. Treatment of MPTPp
      intoxicated mice with PG01037 (30 mg/kg, administrated twice a week for five
      weeks) attenuated the loss of dopaminergic neurons in the substantia nigra pars
      compacta, as evaluated by stereological analysis, and the loss of striatal
      dopaminergic terminals, as determined by densitometric analyses of tyrosine
      hydroxylase and dopamine transporter immunoreactivities. Accordingly, the
      treatment resulted in significant improvement of motor performance of injured
      animals. Interestingly, the therapeutic dose of PG01037 exacerbated astrogliosis
      and resulted in increased ramification density of microglial cells in the
      striatum of MPTPp-intoxicated mice. Further analyses suggested that D3R expressed
      in astrocytes favours a beneficial astrogliosis with anti-inflammatory
      consequences on microglia. Our findings indicate that D3R-antagonism exerts a
      therapeutic effect in parkinsonian animals by reducing the loss of dopaminergic
      neurons in the nigrostriatal pathway, alleviating motor impairments and modifying
      the pro-inflammatory phenotype of glial cells.

PMID- 27693551
TI  - Self-assembled structures and excellent surface properties of a novel anionic
      phosphate diester surfactant derived from natural rosin acids.
AB  - A novel anionic rosin-based phosphate diester sodium (DDPDS) was successfully
      synthesized from raw dehydroabietic acid, a natural raw material, via four-step
      reactions: acylation, esterification, phosphorylation and neutralization. Nuclear
      magnetic resonance (13C NMR) and Fourier transform infrared spectroscopy (FT-IR)
      were used to characterize the structure of target products. The aggregation
      behaviors in aqueous-ethanol solution and surface properties of DDPDS and its
      mixed systems were investigated by transmission electron microscopy (TEM),
      automatic tensiometer and contact angle measuring instrument. The results showed
      that DDPDS had high surface activity, unexpected emulsification and excellent
      wettability. The critical micelle concentration (CMC) of 1.35g*L-1, the minimum
      surface tension (gammacmc) of 31.75mN*m-1, emulsifying power of 153s and the
      minimum contact angle of 13.4 degrees  were determined for DDPDS. Spherical
      vesicles with diameter about 50nm and 5MUm were self-assembled respectively in
      aqueous-ethanol solution when DDPDS concentration is about 1 CMC and 5 CMC. Two
      surfactant ionic self-assembly systems were constructed by mixing DDPDS with
      sodium dodecylbenzenesulfonate (SDBS) and cetyltrimethylammonium bromide (CTAB),
      which forms 40nm and 20nm spherical micelles in 1 CMC aqueous-ethanol solution.
      Possible formation mechanisms of surfactant ionic self-assembly systems on a
      combination of ionic interactions between DDPDS and SDBS or CTAB are discussed.
      It was found that there were an obvious synergistic effect of foam stability in
      DDPDS/SDBS mixed system and an obvious synergistic effect of foam capability in
      DDPDS/CTAB mixed system.

PMID- 27693548
TI  - Towards Personalized Intervention for Alzheimer's Disease.
AB  - Alzheimer's disease (AD) remains to be a grand challenge for the international
      community despite over a century of exploration. A key factor likely accounting
      for such a situation is the vast heterogeneity in the disease etiology, which
      involves very complex and divergent pathways. Therefore, intervention strategies
      shall be tailored for subgroups of AD patients. Both demographic and in-depth
      information is needed for patient stratification. The demographic information
      includes primarily APOE genotype, age, gender, education, environmental exposure,
      life style, and medical history, whereas in-depth information stems from genome
      sequencing, brain imaging, peripheral biomarkers, and even functional assays on
      neurons derived from patient-specific induced pluripotent cells (iPSCs).
      Comprehensive information collection, better understanding of the disease
      mechanisms, and diversified strategies of drug development would help with more
      effective intervention in the foreseeable future.

PMID- 27693552
TI  - Protein oleogels from heat-set whey protein aggregates.
AB  - In this research we use heat-set whey protein aggregates (diameter~200nm) as
      novel building blocks for structure formation in liquid oil to form oleogels. To
      transfer the aggregates to the oil phase, a solvent exchange procedure to
      sunflower oil was applied using acetone as an intermediate solvent. We found that
      agglomeration of the aggregates was prevented and the particle size in oil did
      not change from that in the initial aqueous phase. The small protein aggregates
      assemble into a space-spanning network, thereby providing solid-like properties
      to liquid oil. From oscillatory rheology we conclude that the aggregates are
      highly effective in forming a network. Already at ~3% we found that G'>G" and G'
      scales with protein concentration as G'~cp5.3. Applying a fractal gel network
      theory to the rheological data we deduce that the gels are in the strong link
      regime with a fractal dimension of 2.2. The results show that protein aggregates,
      besides their well-known functionality in aqueous solvents, are capable of
      forming a network in liquid oil. This provides a novel and promising way to
      design oleogels with tuneable rheological properties, applicable to e.g. foods,
      pharmaceuticals and/or cosmetics.

PMID- 27693553
TI  - Natural polysaccharides-modified graphene oxide for adsorption of organic dyes
      from aqueous solutions.
AB  - Three polysaccharide- graphene oxide composite materials (PS-GO) were synthesized
      from graphene oxide (GO) and natural polysaccharides, which compounds were tested
      for removal of organic dyes from aqueous solutions. These adsorbents were
      characterized by Fourier transform infrared spectroscopy (FT-IR), Raman
      spectrometer, X-ray photoelectron spectroscopy (XPS), transmission electron
      microscopy (TEM), scanning electron microscopy (SEM), thermogravimetric analysis
      (TGA), N2 adsorption-desorption isotherms and UV-vis spectrum. The adsorption
      properties of PS-GO towards four organic dyes were investigated along with
      measured effects on adsorption by initial concentration, temperature, contact
      time and pH value. Resulting adsorption isotherms, thermodynamics and kinetics
      were analyzed systematically. In these tests, PS-GO composite materials were
      found to be more efficient than as-prepared GO as adsorbents for the removal of
      both cationic and anionic organic dyes.

PMID- 27693554
TI  - Mechanochemical approach for the capping of mixed core CdS/ZnS nanocrystals:
      Elimination of cadmium toxicity.
AB  - The wet mechanochemical procedure for the capping of the CdS and CdS/ZnS quantum
      dot nanocrystals is reported. l-cysteine and polyvinylpyrrolidone (PVP) were used
      as capping agents. When using l-cysteine, the dissolution of cadmium(II) was
      almost none for CdS/ZnS nanocrystals. Moreover, prepared CdS- and CdS/ZnS
      cysteine nanosuspensions exhibited unimodal particle size distributions with very
      good stability, which was further supported by the zeta potential measurements.
      The Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR)
      spectroscopy showed the successful embedment of cysteine into the structure of
      the nanocrystals. Additionally, the optical properties were examined, and the
      results showed that the cysteine nanosuspension has promising fluorescence
      properties. On the other hand, PVP was not determined to be a very suitable
      capping agent for the present system. In this case, the release of cadmium(II)
      was higher in comparison to the l-cysteine capped samples. The nanosuspensions
      were successfully used for in vitro studies on selected cancer cell lines. Using
      fluorescence microscopy, it was evidenced that the nanocrystals enter the cell
      and that they can serve as imaging agents in biomedical applications.

PMID- 27693555
TI  - Translating leukemia stem cells into the clinical setting: Harmonizing the
      heterogeneity.
AB  - Considerable evidence suggests that rare leukemia cells with stem cell features,
      including self-renewal capacity and drug resistance, are primarily responsible
      for both disease maintenance and relapses. Traditionally, these so-called
      leukemia stem cells (LSCs) have been identified in the laboratory by their
      ability to engraft acute myeloid leukemia (AML) into immunocompromised mice. For
      many years, only those rare AML cells characterized by a hematopoietic stem cell
      (HSC) CD34+CD38- phenotype were believed capable of generating leukemia in
      immunocompromised mice. However, more recently, significant heterogeneity in the
      phenotypes of those AML cells that can engraft immunocompromised mice has been
      demonstrated. AML cells that engraft immunocompromised mice have also been shown
      to not necessarily represent either the founder clone or those cells responsible
      for relapse. A recent study found that the most immature phenotype present in an
      AML correlated with genetically defined risk groups and outcomes, but was
      heterogeneous. Patients with AML cells expressing a primitive HSC phenotype
      (CD34+CD38- with high aldehyde dehydrogenase activity) manifested significantly
      lower complete remission rates, as well as poorer event-free and overall
      survivals. Leukemias in which the most primitive cells displayed more mature
      phenotypes were associated with better outcomes. The strong clinical correlations
      suggest that the most immature phenotype detectable within a patient's AML might
      serve as a biomarker for "clinically relevant" LSCs.

PMID- 27693557
TI  - Dye-conjugated single-walled carbon nanotubes induce photothermal therapy under
      the guidance of near-infrared imaging.
AB  - Recently, photothermal therapy (PTT) has become viewed as an ideal auxiliary
      therapeutic treatment for cancers. However, the development of safe, convenient,
      and highly effective photothermal agents remains a great challenge. In this
      study, we prepared single-walled carbon nanotubes (SWNTs) for PTT against breast
      tumors under the guidance of infrared fluorescent cyanines. Tumors were
      accurately located using near-infrared imaging (NIR) and then exposed to laser
      irradiation. Both the in vivo and in vitro results showed that the SWNTs have
      high stability and low cytotoxicity. Introducing polyethylene glycol into our
      nanoparticles increased the blood-circulation time. Our in vivo results further
      showed that Cy5.5-conjugated SWNTs mediated PTT, resulting in efficient tumor
      suppression in mice under the guidance of near-infrared imaging. Due to the small
      amount of absorption at 808-nm, Cy5.5 increased the efficiency of PTT. Breast
      tumors significantly shrunk after irradiation under the 808-nm near-infrared
      laser. The treated mice developed scabs, but otherwise recovered after 15 days,
      and their physical conditions restored gradually. These data indicate that our
      unique photothermal-responsive SWNT-Cy5.5-based theranostic agent can serve as a
      promising candidate for PTT.

PMID- 27693558
TI  - Lgr4 is crucial for skin carcinogenesis by regulating MEK/ERK and Wnt/beta
      catenin signaling pathways.
AB  - Lgr4 is a member of the leucine-rich, G protein-coupled receptor family of
      proteins, and has recently been shown to augment Wnt/beta-catenin signaling via
      binding to Wnt agonists R-spondins. It plays an important role in skin
      development, but its involvement in skin tumorigenesis is unclear. Here, we
      report that mice deficient for Lgr4 are resistant to 12-O-tetradecanoyl-phorbol
      13-acetate (TPA)-induced keratinocyte proliferation and papilloma formation. We
      show that TPA treatment activates MEK1, ERK1/2 and downstream effector AP-1 in
      wild-type (WT) epidermal cells and mice, but not in cells or mice where Lgr4 is
      depleted. Wnt/beta-catenin signaling is also dramatically activated by TPA
      treatment, and this activation is abolished when Lgr4 is deleted. We provide
      evidences that blocking both MEK1/ERK1/2 and Wnt/beta-catenin pathways prevents
      TPA-induced increase in the expression of Ccnd1 (cyclin D1), a known Wnt/beta
      catenin target gene, and that the activation of MEK1/ERK1/2 pathway lies upstream
      of Wnt/beta-catenin signal pathway. Collectively, our findings identify Lgr4 as a
      critical positive factor for skin tumorigenesis by mediating the activation of
      MEK1/ERK1/2 and Wnt/beta-catenin pathways.

PMID- 27693559
TI  - Morphology and molecular phylogeny of a new Myxidium species (Cnidaria:
      Myxosporea) infecting the farmed turtle Podocnemis expansa (Testudines:
      Podocnemididae) in the Brazilian Amazon.
AB  - This study reports, for the first time, a myxosporan species of the genus
      Myxidium in a Neotropical turtle. Myxidium turturibus n. sp., was found in the
      gall bladder of Podocnemis expansa (Testudines: Podocnemididae) farmed in
      Brazilian Amazon. Numerous disporic pseudoplasmodia in different developmental
      stages, and mature spores were free in the bile. Mature myxospores were fusiform,
      slightly arcuate in valval view, measuring 13.6+/-0.4 (13.1-15.1) MUm in length
      and 4.1+/-0.3 (3.4-4.6) MUm in width. The two polar capsules were piriform, with
      3.4+/-0.4 (2.5-4.0) MUm in length and 2.4+/-0.4 (1.5-2.7) MUm in width and had
      five to six polar filament turns. Phylogenetic analysis inferred by 18S rDNA
      shows the new species closely related with M. hardella and M. chelonarum, which
      are parasites of freshwater/terrestrials turtles from Oriental Region.

PMID- 27693556
TI  - Anti-tumor activity of selective inhibitor of nuclear export (SINE) compounds, is
      enhanced in non-Hodgkin lymphoma through combination with mTOR inhibitor and
      dexamethasone.
AB  - In previous studies we demonstrated that targeting the nuclear exporter protein
      exportin-1 (CRM1/XPO1) by a selective inhibitor of nuclear export (SINE) compound
      is a viable therapeutic strategy against Non-Hodgkin Lymphoma (NHL). Our studies
      along with pre-clinical work from others led to the evaluation of the lead SINE
      compound, selinexor, in a phase 1 trial in patients with CLL or NHL
      (NCT02303392). Continuing our previous work, we studied combinations of selinexor
      dexamethasone (DEX) and selinexor-everolimus (EVER) in NHL. Combination of
      selinexor with DEX or EVER resulted in enhanced cytotoxicity in WSU-DLCL2 and WSU
      FSCCL cells which was consistent with enhanced apoptosis. Molecular analysis
      showed enhancement in the activation of apoptotic signaling and down-regulation
      of XPO1. This enhancement is consistent with the mechanism of action of these
      drugs in that both selinexor and DEX antagonize NF-kappaB (p65) and mTOR (EVER
      target) is an XPO1 cargo protein. SINE compounds, KPT-251 and KPT-276, showed
      activities similar to CHOP (cyclophosphamide-hydroxydaunorubicin-oncovin
      prednisone) regimen in subcutaneous and disseminated NHL xenograft models in
      vivo. In both animal models the anti-lymphoma activity of selinexor is enhanced
      through combination with DEX or EVER. The in vivo activity of selinexor and
      related SINE compounds relative to 'standard of care' treatment is consistent
      with the objective responses observed in Phase I NHL patients treated with
      selinexor. Our pre-clinical data provide a rational basis for testing these
      combinations in Phase II NHL trials.

PMID- 27693560
TI  - Differential distribution and biochemical characteristics of hydrolases among
      developmental stages of Schistosoma mansoni may offer new anti-parasite targets.
AB  - Schistosoma mansoni enzymes play important roles in host-parasite interactions
      and are potential targets for immunological and/or pharmacological attack. The
      aim of this study was to comparatively assess the presence of hydrolytic
      activities (phosphatases, glycosidases, aminopeptidases) in soluble (SF) and
      membrane (MF) fractions from different S. mansoni developmental stages
      (schistosomula 0 and 3h, juveniles, and adult worms of 28 and 45days-old,
      respectively), by using simple enzyme-substrate microassays. Our results show and
      confirm the prominent presence of alkaline phosphatase (AlP) activity in the MF
      of all the above parasite stages, highlighting also the relevant presence of MF
      associated alpha-mannosidase (alpha-MAN) activity in juveniles. A soluble AlP
      activity, together with beta-N-D-acetylglucosaminidase (beta-NAG), and alpha-MAN
      activities, was detected in SF of schistosomulum 0h. Soluble beta-NAG, alpha-MAN,
      acid phosphatase (AcP), leucin (LAP) and alanine (AAP) aminopeptidase activities
      were also seen in the SF of the other different developmental stages. This work
      shows different soluble and membrane-associated hydrolytic capacities in each S.
      mansoni developmental stage from schistosomula to adults that might be
      exploitable as potential new targets for immune and/or chemoprophylactic
      strategies.

PMID- 27693561
TI  - Transplantation of Cardicola opisthorchis (Trematoda: Aporocotylidae) sporocysts
      into the intermediate host, Terebella sp. (Polychaeta: Terebellidae).
AB  - Cardicola opisthorchis is a blood fluke pathogen significantly affecting cultured
      Pacific bluefin tuna Thunnus orientalis in Japan. It is known that the
      intermediate host of C. opisthorchis is a terebellid polychaete Terebella sp. In
      order to study the intrapolychaete larval development of C. opisthorchis, we
      transplanted sporocysts, which contained a large number of cercariae, of C.
      opisthorchis obtained from Terebella sp. into sporocyst-free Terebella sp., which
      had been maintained at 20 degrees C. The transplanted sporocysts switched from
      cercarial to sporocystal production by 17days after transplantation (d.a.t.) and
      daughter sporocysts were released into the polychaete body cavity at 25d.a.t.
      Subsequently, the released daughter sporocysts produced daughter sporocysts
      again. Thereafter, daughter sporocysts that contained cercariae appeared at
      38d.a.t. and gradually increased. At 51d.a.t., 136 sporocysts that had multiplied
      from the original two transplanted sporocysts were observed in the body of one
      polychaete, and cercariae were released from daughter sporocysts inside the
      polychaete body cavity. Subsequently the cercariae were found to be released
      outside the polychaete at 57d.a.t. This is the first successful case of in situ
      observation of the development of a blood fluke within the intermediate host.

PMID- 27693562
TI  - Editorial: 3rd Special Issue on behavior change, health, and health disparities.
AB  - This Special Issue of Preventive Medicine (PM) is the 3rd that we have organized
      on behavior change, health, and health disparities. This is a topic of critical
      importance to improving U.S. population health. There is broad scientific
      consensus that personal behaviors such as cigarette smoking, other substance
      abuse, and physical inactivity/obesity are among the most important modifiable
      causes of chronic disease and its adverse impacts on population health. Hence,
      effectively promoting health-related behavior change needs to be a key component
      of health care research and policy. There is also broad recognition that while
      these problems extend throughout the population, they disproportionately impact
      economically disadvantaged populations and other vulnerable populations and
      represent a major contributor to health disparities. Thus, behavior change
      represents an essential step in curtailing health disparities, which receives
      special attention in this 3rd Special Issue. We also devote considerable space to
      the longstanding challenges of reducing cigarette smoking and use of other
      tobacco and nicotine delivery products in vulnerable populations, obesity, and
      for the first time food insecurity. Across each of these topics we include
      contributions from highly accomplished policymakers and scientists to acquaint
      readers with recent accomplishments as well as remaining knowledge gaps and
      challenges.

PMID- 27693563
TI  - Biomechanical arrangement of threaded and unthreaded portions providing holding
      power of transpedicular screw fixation.
AB  - BACKGROUND: Failure of pedicle screw is a major concern in spinal surgery. The
      threaded and unthreaded portions of the pedicle screw provide the ability to
      anchor and squeeze the surrounding bone, respectively. This study aimed to
      investigate the anchoring and squeezing effects of different design of the
      threaded/unthreaded portions of a pedicle screw to vertebrae. METHODS: Four
      variations (one fully and three partially threaded, with a 1/3, 1/2, and 2/3
      unthreaded designs at the proximal portion) of screws were used to measure
      pullout strength and withdrawn energy using synthetic and porcine specimens. The
      tests were conducted in static and dynamic fashions, in that the screws were
      axially extracted directly and after 150,000cycles of lateral bending. The load
      displacement curves were recorded to gain insight into the peak load (pullout
      strength) and cumulative work (withdrawn energy). FINDINGS: The two testing
      results of the synthetic and porcine specimens consistently showed that the 1/3
      unthreaded screw provides significantly higher pullout strength and withdrawn
      energy than the fully threaded screw. The withdrawn energy of the three
      unthreaded screws was significantly higher than that of the threaded counterpart.
      INTERPRETATION: The holding power of a pedicle screw was the integration of the
      anchoring (cancellous core) and squeezing (compact pedicle) effects within the
      threaded and unthreaded portions. The current study recommends the 1/3 unthreaded
      screw as an optimal alternative for use as a shank-sliding mechanism to preserve
      the holding power within the pedicle isthmus.

PMID- 27693564
TI  - Promotion of active ageing combining sensor and social network data.
AB  - The increase of life expectancy in modern society has caused an increase in
      elderly population. Elderly people want to live independently in their home
      environment for as long as possible. However, as we age, our physical skills tend
      to worsen and our social circle tends to become smaller, something that often
      leads to a considerable decrease of both our physical and social activities. In
      this paper, we present an AAL framework developed within the SONOPA project,
      whose objective is to promote active ageing by combining a social network with
      information inferred using in-home sensors.

PMID- 27693565
TI  - The Learning Healthcare System: Where are we now? A systematic review.
AB  - BACKGROUND AND OBJECTIVE: The Learning Healthcare System paradigm has attracted
      the attention of researchers worldwide. The great potential originating from high
      scale health data reuse and the inclusion of patient perspectives into care
      models promises personalized care, lower costs of health services and minimized
      consumption of resources. The aim of this review is to summarize the attempts to
      adopt the novel paradigm, putting emphasis on implementations and evaluating the
      impact on current medical practices. METHOD: PRISMA methodology was followed for
      structuring the review process. Three major research databases (PubMed, IEEE
      Xplore and ACM DL) were queried with the predefined search terms "learning
      healthcare" and "learning health". Publications containing specific theoretical
      or empirical results were considered. RESULTS: Three hundred and fifty-eight
      publications were identified; however, only 32 met the inclusion criteria.
      Nineteen papers were characterized as theoretical contributions, while the rest
      presented empirical achievements. Only one paper described the initial estimates
      of impact and economy. DISCUSSION: Individualistic communication of studies
      ignoring popular frameworks for assessing and reporting research achievements
      prevents the systematic generation of knowledge. Evaluating the impact of the
      Learning Healthcare System instances where it is implemented could work as a
      catalyst in reaching higher acceptance and adoption of the proposed ideas by
      healthcare worldwide; however, it mostly remains described in theory.
      CONCLUSIONS: The review demonstrated the interest of researchers in exploring the
      Learning Healthcare System ideas. However, it also revealed minimal focus on
      evaluating the impact of the novel paradigm on both healthcare service delivery
      and patient outcome.

PMID- 27693566
TI  - The effects of poloxamer 188 on the autophagy induced by traumatic brain injury.
AB  - Poloxamer 188 (P188) has been reported to reseal plasma membranes and attenuate
      TBI-induced neuronal death by suppressing apoptosis. Recent studies also confirm
      increased autophagy after traumatic brain injury (TBI). The present study aimed
      to investigate the effects of plasmalemmal resealing by P188 on neuronal
      autophagy in TBI. Scratch test was performed in rat cell line PC-12 in vitro,
      followed by immunofluorescence analysis of LC3 24h after PC-12 cell stretch
      injury in vitro. CD1 mice were randomized into saline and P188-treatment groups
      (both undergoing intravenous injection of 4mg/ml, 100MUl via the caudal vein
      30min after TBI) as well as sham group. To analyze the effect of P188 on
      autophagy, the LC3 protein levels were assessed by western blotting 1h, 6h, 12h,
      24h, and 48h after TBI. The autophagy-associated protein levels of Beclin-1, Bcl
      2, and p62 were likewise determined. In vitro, the scratch test showed that the
      wound healing rate was significantly improved at 12h and 24h in P188 groups, and
      LC3 immunofluorescence analysis indicated that P188 induced extensive formation
      of LC3 puncta in PC-12 cells. In vivo, western blotting analyses revealed
      elevations of the LC3-II/LC3-I and Beclin-1/bcl-2 ratios as well as
      downregulation of p62 in the saline group, in contrast with the more significant
      increases of LC3-II/LC3-I and Beclin-1/bcl-2 ratios and the further
      downregulation of p62 in P188-treated group. These results revealed that plasma
      membranes were resealed after TBI, in which P188 aggravated autophagy in vivo.

PMID- 27693567
TI  - The African clawed frog Xenopus laevis: A model organism to study regeneration of
      the central nervous system.
AB  - While an injury to the central nervous system (CNS) in humans and mammals is
      irreversible, amphibians and teleost fish have the capacity to fully regenerate
      after severe injury to the CNS. Xenopus laevis has a high potential to regenerate
      the brain and spinal cord during larval stages (47-54), and loses this capacity
      during metamorphosis. The optic nerve has the capacity to regenerate throughout
      the frog's lifespan. Here, we review CNS regeneration in frogs, with a focus in
      X. laevis, but also provide some information about X. tropicalis and other frogs.
      We start with an overview of the anatomy of the Xenopus CNS, including the main
      supraspinal tracts that emerge from the brain stem, which play a key role in
      motor control and are highly conserved across vertebrates. We follow with the
      advantages of using Xenopus, a classical laboratory model organism, with
      increasing availability of genetic tools like transgenesis and genome editing,
      and genomic sequences for both X. laevis and X. tropicalis. Most importantly,
      Xenopus provides the possibility to perform intra-species comparative experiments
      between regenerative and non-regenerative stages that allow the identification of
      which factors are permissive for neural regeneration, and/or which are
      inhibitory. We aim to provide sufficient evidence supporting how useful Xenopus
      can be to obtain insights into our understanding of CNS regeneration, which,
      complemented with studies in mammalian vertebrate model systems, can provide a
      collaborative road towards finding novel therapeutic approaches for injuries to
      the CNS.

PMID- 27693568
TI  - Nonviral vector plasmid DNA encoding human proenkephalin gene attenuates
      inflammatory and neuropathic pain-related behaviors in mice.
AB  - Inflammatory pain and neuropathic pain are major clinical health issues that
      represent considerable social and economic burden worldwide. In the present
      study, we investigated the anti-nociceptive efficacy of delivery of human
      proenkephalin gene by a plasmid DNA vector (pVAX1-PENK) on complete Freund's
      adjuvant (CFA) induced inflammatory pain and spared nerve injury (SNI) induced
      neuropathic pain in mice. Mice were intramuscularly or intrathecally administered
      pVAX1 or pVAX1-PENK, respectively. Pain thresholds in the pVAX1-PENK treated mice
      were significantly higher at day 3, then reached a peak at day 7 and lasted until
      day 28 after gene transfer, and the analgesic effect of pVAX1-PENK was blocked
      with naloxone hydrochloride. In contrast, pVAX1 treated mice did not
      significantly improve pain thresholds. These results indicate that peripheral or
      spinal delivery of a plasmid encoding human proenkephalin gene provides a
      potential therapeutic strategy for inflammatory pain and neuropathic pain.

PMID- 27693569
TI  - Accurate annotation of protein-coding genes in mitochondrial genomes.
AB  - Mitochondrial genome sequences are available in large number and new sequences
      become published nowadays with increasing pace. Fast, automatic, consistent, and
      high quality annotations are a prerequisite for downstream analyses. Therefore,
      we present an automated pipeline for fast de novo annotation of mitochondrial
      protein-coding genes. The annotation is based on enhanced phylogeny-aware hidden
      Markov models (HMMs). The pipeline builds taxon-specific enhanced multiple
      sequence alignments (MSA) of already annotated sequences and corresponding HMMs
      using an approximation of the phylogeny. The MSAs are enhanced by fixing
      unannotated frameshifts, purging of wrong sequences, and removal of non-conserved
      columns from both ends. A comparison with reference annotations highlights the
      high quality of the results. The frameshift correction method predicts a large
      number of frameshifts, many of which are unknown. A detailed analysis of the
      frameshifts in nad3 of the Archosauria-Testudines group has been conducted.

PMID- 27693570
TI  - Gene duplication and concerted evolution of mitochondrial DNA in crane species.
AB  - The gene duplication in mitochondrial DNA (mtDNA) has been reported in diverse
      bird taxa so far. Although many phylogenetic and population genetic analyses of
      cranes were carried out based on mtDNA diversity, whether mtDNA contains
      duplicated regions is unknown. To address the presence or absence of gene
      duplication in cranes and investigate the molecular evolutionary features of
      crane mtDNA, we analyzed the gene organization and the molecular phylogeny of
      mtDNA from 13 crane species. We found that the mtDNA in 13 crane species shared a
      tandem duplicated region, which consists of duplicated sequence sets including
      cytochrome b (Cytb), NADH6, control region (CR) and three genes of tRNA. The gene
      order in the duplicated region was identical among all the 13 crane species, and
      the nucleotide sequences found within each individual showed high similarities.
      In addition, phylogenetic trees based on homologous sequences of CR and Cytb
      indicated the possibility of concerted evolution among the duplicated genes. The
      results suggested that the duplication event occurred in the common ancestor of
      crane species or some older ancestors.

PMID- 27693571
TI  - Better Defining the Spectrum of Adult Hypospadias: Examining the Effect of
      Childhood Surgery on Adult Presentation.
AB  - OBJECTIVE: To describe the spectrum of adult presentations with hypospadias
      related complications and examine the effect of childhood surgical repair on
      these adult presentations. METHODS: A retrospective chart review over a 10-year
      period, from August 2004 to December 2014, demonstrated 93 adult patients who
      presented to a reconstructive urologist with complications related to
      hypospadias. Patients were divided into 2 groups: those with no prior hypospadias
      surgery (Group 1, N = 19) and those who underwent surgical correction as a child
      (Group 2, N = 74). Charts were reviewed for age at presentation, initial
      complaints, history of repair, and surgical intervention required. RESULTS: The
      mean age at presentation was 34.6 +/- 0.6 years. Overall, lower urinary tract
      symptoms (LUTS) (49%) was the most common presenting complaint, followed by
      spraying (24%), urethrocutaneous fistula (18%), recurrent urinary tract
      infections (UTIs) (15%), and chordee (14%). Comparison demonstrated that Group 2
      patients were more likely to present with LUTS (55% vs 26%; P = .038) and
      recurrent UTIs (19% vs 0%; P = .050). There was a trend toward Group 1 patients
      presenting more commonly with cosmetic dissatisfaction (16% vs 4%; P = .06).
      Urethral stricture was demonstrated more commonly in Group 2 (47% vs 11%; P =
      .0043). Of these, strictures were significantly longer in the previous surgery
      group (5.5 +/- 0.6 cm vs 3.0 +/- 0.6 cm, P = .019). CONCLUSION: Correction of
      hypospadias as a child likely increases the future risk of urethral stricture,
      recurrent UTIs, and subsequent LUTS, with a trend toward improving patient
      satisfaction with cosmesis compared to nonsurgical management. Follow-up of
      hypospadias repair patients should extend into adulthood, as a significant
      portion of adult presentations ultimately require surgical intervention.

PMID- 27693572
TI  - Contemporary Trends in the Inpatient Management of Fournier's Gangrene:
      Predictors of Length of Stay and Mortality Based on Population-based Sample.
AB  - OBJECTIVE: To describe clinical management of Fournier's gangrene and to
      characterize predictive factors associated with inpatient mortality and extended
      hospital stay. MATERIALS AND METHODS: The National Inpatient Sample was queried
      from 2004 to 2012 based on the International Classification of Diseases, Ninth
      Revision, Clinical Modification procedural and diagnosis codes. Patients admitted
      for Fournier's gangrene who underwent debridement were selected. Multivariate
      logistic regression analysis was performed to identify predictors of inpatient
      mortality and extended hospital stay. RESULTS: A total of 9249 patients were
      identified for a weighted estimate of 43,146 cases. Inpatient mortality was 4.7%.
      The median length of stay was 9 days (interquartile range 5-17 days). The most
      common procedure in addition to debridement was a complex closure (8.82%),
      followed by suprapubic tube placement (5.70%) and fecal diversion (4.68%).
      Increasing age, yearly hospital volume >10 cases, and Medicaid insurance status
      were associated with increased risk of mortality. Increasing age, teaching
      hospital status, increasing number of comorbidities, and Medicaid as a payor were
      predictive of increased hospital stay. Suprapubic tube placement (odds ratio [OR]
      2.8 [95% confidence interval {CI} 1.92-4.07], P <= .001), fecal diversion (OR
      11.1 [95% CI 6.20-19.7], P <= .001), and complex wound closure (OR 4.89 [95% CI
      3.97-6.89], P <= .001) were also predictive of increased length of stay.
      CONCLUSION: Identifiable patient and hospital characteristics are predictive of
      both mortality and length of stay in the management of Fournier's gangrene.
      Overall inpatient mortality appears lower than what has been reported in the
      majority of prior reports. The strongest predictor for increased length of stay
      is the need for complex wound closure, and urinary or fecal diversion.

PMID- 27693573
TI  - Re: Churukanti et al: Role of Ultrasonography for Testicular Injuries in
      Penetrating Scrotal Trauma (Urology 2016;95:208-212).

PMID- 27693574
TI  - Hybrid Transvaginal NOTES Nephrectomy: Postoperative Sexual Outcomes. A Three
      center Matched Study.
AB  - OBJECTIVE: To evaluate our experience in patients undergoing hybrid transvaginal
      natural orifices transluminal endoscopic surgery (NOTES) nephrectomy and evaluate
      the sexual functions in the postoperative period. MATERIALS AND METHODS:
      Prospective data of 71 patients with renal tumors who underwent hybrid NOTES
      radical nephrectomy in three different centers were collected from March 2010 to
      October 2015. Patient and surgical characteristics were recorded. Sexual function
      was evaluated using the Female Sexual Function Index questionnaire the day prior
      to the operation and 3 months after. RESULTS: The mean age, tumor size, and
      operation duration were 66.16 +/- 11.21, 8.51 +/- 3.31 cm, and 119.94 +/- 21.38
      minutes, respectively. Five patients were immediately reoperated due to bleeding
      from uterine veins. The complication risk increases significantly with increasing
      tumor size. Among the whole cohort, even the Female Sexual Function Index score
      differences are small; there is a statistically significant decrease in the
      postoperative period in all domains except sexual satisfaction. In fact, the
      patients reported unaltered sexual function after surgery and satisfaction with
      the result when asked directly. In subgroup analyses, in nulliparous patients (n
      = 60), arousal, sexual desire, orgasm, and satisfaction domains have no
      significant differences in pre- and postoperative periods. CONCLUSIONS: Hybrid
      NOTES nephrectomy is a feasible, safe operation that can be performed for large
      renal tumors. Due to incisions in the vaginal wall for specimen retrieval, sexual
      function can be altered in the postoperative period. So patient selection,
      preoperative evaluation, and close follow-up are mandatory. With this in mind, we
      strongly support the use of hybrid transvaginal NOTES nephrectomy for large renal
      tumors especially in nulliparous patients.

PMID- 27693576
TI  - Immunochemical evaluation of two Toxoplasma gondii GRA8 sequences to detect acute
      toxoplasmosis infection.
AB  - In this work, two Toxoplasma gondii GRA8 protein sequences were tested by
      indirect ELISA and measurement of avidity to differentiate between acute and
      chronic toxoplasmosis infection. Using the antigen called GRA8B, 79.7%
      sensitivity and 84.1% specificity was achieved detecting IgG concentrations and a
      71.2% sensitivity and a 68.3% specificity detecting IgA concentrations. This
      study is the first to report IgA detection with GRA8 by ELISA to differentiate
      stages of infection. Unfortunately the indirect ELISA to detect IgM was not
      effective in distinguishing stages. Also, this work is the first to report that
      the GRA8 protein can aid the differentiation between acute and chronic phase
      infection by measuring IgG antibody avidity, a technique in which we obtained
      85.71% and 100% of sensitivity and specificity, respectively. Finally, in silico
      tools were used to explain the differences in our immunochemistry results.

PMID- 27693575
TI  - Stress reactivity and personality in extreme sport athletes: The psychobiology of
      BASE jumpers.
AB  - This is the first report of the psychobiology of stress in BASE jumpers, one of
      the most dangerous forms of extreme sport. We tested the hypotheses that
      indicators of emotional style (temperament) predict salivary cortisol reactivity,
      whereas indicators of intentional goal-setting (persistence and character)
      predict salivary alpha-amylase reactivity during BASE jumping. Ninety-eight
      subjects completed the Temperament and Character Inventory (TCI) the day before
      the jump, and 77 also gave salivary samples at baseline, pre-jump on the bridge
      over the New River Gorge, and post-jump upon landing. Overall BASE jumpers are
      highly resilient individuals who are highly self-directed, persistent, and risk
      taking, but they are heterogeneous in their motives and stress reactivity in the
      Hypothalamic-Pituitary-Adrenal (HPA) stress system (cortisol reactivity) and the
      sympathetic arousal system (alpha-amylase reactivity). Three classes of jumpers
      were identified using latent class analysis based on their personality profiles,
      prior jumping experience, and levels of cortisol and alpha-amylase at all three
      time points. "Masterful" jumpers (class 1) had a strong sense of self
      directedness and mastery, extensive prior experience, and had little alpha
      amylase reactivity and average cortisol reactivity. "Trustful" jumpers (class 2)
      were highly cooperative and trustful individuals who had little cortisol
      reactivity coincident with the social support they experienced prior to jumping.
      "Courageous" jumpers (class 3) were determined despite anxiety and inexperience,
      and they had high sympathetic reactivity but average cortisol activation. We
      conclude that trusting social attachment (Reward Dependence) and not jumping
      experience predicted low cortisol reactivity, whereas persistence (determination)
      and not jumping experience predicted high alpha-amylase reactivity.

PMID- 27693577
TI  - Antifungal activity of eicosanoic acids isolated from the endophytic fungus
      Mycosphaerella sp. against Cryptococcus neoformans and C. gattii.
AB  - The antifungal effects of two eicosanoic acids, 2-amino-3,4-dihydroxy-2-25
      (hydroxymethyl)-14-oxo-6,12-eicosenoic acid (compound 1) and myriocin (compound
      2), isolated from Mycosphaerella sp. were evaluated against Cryptococcus
      neoformans and C. gattii. The compounds displayed antifungal activities against
      several isolates of C. neoformans and C. gattii, with minimal inhibitory
      concentration (MIC) values ranging from 0.49 to 7.82 MUM for compound 1 and 0.48
      1.95 MUM for compound 2. In the checkerboard microtiter test, both compounds
      exhibited synergistic activity with amphotericin B against C. gattii.
      Ultrastructural analysis revealed several signs of damage in C. gattii and C.
      neoformans cells treated with compounds 1 and 2, including deformities in cell
      shape, depressions on the surface, and withered cells. The cells of C. gattii
      treated with compounds 1 and 2 showed less loss of cellular material in
      comparison to those treated with amphotericin B. The difference in cellular
      material loss increased in a test compound concentration-dependent manner.
      Consistent with this observation, compounds 1 and 2 were able to internalize
      propidium iodide (PI) in C. gattii cells. In addition, compound 2 induced the
      formation of several pseudohyphae, suggesting that it could reduce virulence in
      C. gattii cells. The study results show that these natural products led to
      membrane damage; however, this may not be the main target of action. These
      compounds have potential antifungal activity and could be useful in further
      studies for developing more effective combination therapies with amphotericin B
      and reducing side effects in patients.

PMID- 27693578
TI  - The E3 ubiquitin ligase c-Cbl mediates integrin beta1 ubiquitination during
      dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is characterized by dilatation of the ventricular
      chambers and impaired myocardial contractility. The results of our previous study
      indicated that a deficiency in matricellular cartilage oligomeric matrix protein
      (COMP) led to spontaneous and progressive DCM in mice via the
      ubiquitination/degradation of integrin beta1. However, the specific ubiquitin
      enzyme involved in degradation of integrin beta1 and the pathogenesis of DCM
      remain elusive. We first compared gene expression profiles in hearts from 3-month
      old wild type and COMP-/- mice using microarray analysis. Among the E3 ubiquitin
      ligases upregulated in COMP-/- hearts, c-Cbl silencing rescued the
      ubiquitination/degradation of integrin beta1, myofilament loss, apoptosis and
      connexin-43 deficiency in cardiomyocytes due to the silencing of COMP.
      Furthermore, c-Cbl silencing by intramyocardial injections of siRNA into 1-month
      old COMP-/- mice ameliorated spontaneous DCM in vivo, as evidenced by the
      inhibition of the dilation of ventricular chambers, impaired ejection fraction
      and myofilament loss. A subsequent cellular ubiquitination assay revealed that
      overexpression of c-Cbl induced ubiquitination of integrin beta1, whereas the
      G306E mutation in c-Cbl, which prevented the binding of c-Cbl to its substrates,
      had no effect on integrin beta1 ubiquitination, indicating that c-Cbl directly
      caused the ubiquitination of integrin beta1 in the hearts. In conclusion, our
      results demonstrate that c-Cbl mediates the ubiquitination/degradation of
      integrin beta1, which leads to COMP deficiency-induced DCM.

PMID- 27693579
TI  - The oxoglutarate receptor 1 (OXGR1) modulates pressure overload-induced cardiac
      hypertrophy in mice.
AB  - The G-protein-coupled receptors (GPCRs) family of proteins play essential roles
      in the heart, including in the regulation of cardiac hypertrophy. One member of
      this family, the oxoglutarate receptor 1 (OXGR1), may have a crucial role in the
      heart because it acts as a receptor for alpha-ketoglutarate, a metabolite that is
      elevated in heart failure patients. OXGR1 is expressed in the heart but its
      precise function during cardiac pathophysiological process is unknown. Here we
      used both in vivo and in vitro approaches to investigate the role of OXGR1 in
      cardiac hypertrophy. Genetic ablation of Oxgr1 in mice (OXGR1-/-) resulted in a
      significant increase in hypertrophy following transverse aortic constriction
      (TAC). This was accompanied by reduction in contractile function as indicated by
      cardiac fractional shortening and ejection fraction. Conversely, adenoviral
      mediated overexpression of OXGR1 in neonatal rat cardiomyocytes significantly
      reduced phenylephrine-induced cardiomyocyte hypertrophy, a result that was
      consistent with the in vivo data. Using a combination of yeast two hybrid
      screening and phospho-antibody array analysis we identified novel interacting
      partner and downstream signalling pathway that might be regulated by the OXGR1.
      First, we found that OXGR1 forms a molecular complex with the COP9 signalosome
      complex subunit 5 (CSN5). Secondly, we observed that the STAT3 signalling pathway
      was upregulated in OXGR1-/- hearts. Since CSN5 interacts with TYK2, a major
      upstream regulator of STAT3, OXGR1 might regulate the pro-hypertrophic STAT3
      pathway via interaction with the CSN5-TYK2 complex. In conclusion, our study has
      identified OXGR1 as a novel regulator of pathological hypertrophy via the
      regulation of the STAT3. Identification of molecules that can specifically
      activate or inhibit this receptor may be very useful in the development of novel
      therapeutic approach for pathological cardiac hypertrophy.

PMID- 27693580
TI  - Activin pathway enhances colorectal cancer stem cell self-renew and tumor
      progression.
AB  - Activin belongs to transforming growth factor (TGF)-beta super family of growth
      and differentiation factors and activin pathway participated in broad range of
      cell process. Studies elaborated activin pathway maintain pluripotency in human
      stem cells and suggest that the function of activin/nodal signaling in self-renew
      would be conserved across embryonic and adult stem cells. In this study, we tried
      to determine the effect of activin signaling pathway in regulation of cancer stem
      cells as a potential target for cancer therapy in clinical trials. A population
      of colorectal cancer cells was selected by the treatment of activin A. This
      population of cell possessed stem cell character with sphere formation ability.
      We demonstrated activin pathway enhanced the colorectal cancer stem cells self
      renew and contribute to colorectal cancer progression in vivo. Targeting activin
      pathway potentially provide effective strategy for colorectal cancer therapy.

PMID- 27693581
TI  - Fasting boosts sensitivity of human skin melanoma to cisplatin-induced cell
      death.
AB  - Melanoma is one of leading cause of tumor death worldwide. Anti-cancer strategy
      includes combination of different chemo-therapeutic agents as well as radiation;
      however these treatments have limited efficacy and induce significant toxic
      effects on healthy cells. One of most promising novel therapeutic approach to
      cancer therapy is the combination of anti-cancer drugs with calorie restriction.
      Here we investigated the effect Cisplatin (CDDP), one of the most potent
      chemotherapeutic agent used to treat tumors, in association with fasting in wild
      type and mutated BRAFV600E melanoma cell lines. Here we show that nutrient
      deprivation can consistently enhance the sensitivity of tumor cells to cell death
      induction by CDDP, also of those malignancies particularly resistant to any
      treatment, such as oncogenic BRAF melanomas. Mechanistic studies revealed that
      the combined therapy induced cell death is characterized by ROS accumulation and
      ATF4 in the absence of ER-stress. In addition, we show that autophagy is not
      involved in the enhanced sensitivity of melanoma cells to combined CDDP/EBSS
      induced apoptosis. While, the exposure to 2-DG further enhanced the apoptotic
      rate observed in SK Mel 28 cells upon treatment with both CDDP and EBSS.

PMID- 27693582
TI  - Proteasome inhibitor MG132 impairs autophagic flux through compromising formation
      of autophagosomes in Bombyx cells.
AB  - MG132 has been used as a proteasome inhibitor on Bombyx cells, but its
      physiological effects on autophagy still have not been elucidated. In this study,
      we find that the lipidated BmAtg8, BmAtg8-PE as an autophagosomal marker protein,
      is only localized to membranes. Then we established systems to monitor autophagic
      flux in Bombyx cells: Induction of autophagy reduces exogenous BmAtg8 and
      exogenous BmAtg8-PE, facilitates formation of autophagosomes indicated by green
      EGFP-BmAtg8 puncta after cotreatment by Rapamycin and Bafilomycin A1, and causes
      accumulation of free EGFP from EGFP-BmAtg8 cleavage in autolysosomes. Using these
      established systems, we find that exposure of MG132 inhibits both basal and
      Rapamycin-induced autophagy when polyubiquitinated proteins are accumulated
      markedly in Bombyx cells. Interestingly, we reveal that attenuation of autophagy
      in these cells is ascribed as distinct suppression of formation of autophagosomes
      after MG132 treatment.

PMID- 27693583
TI  - vIRF3 encoded by Kaposi's sarcoma-associated herpesvirus inhibits T-cell factor
      dependent transcription via a CREB-binding protein-interaction motif.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is an etiological agent of
      Kaposi's sarcoma and primary effusion lymphoma. Like other herpesviruses, KSHV
      has two distinct life cycles: latent and lytic. Among KSHV latent genes, viral
      interferon regulatory factor 3 (vIRF3), which shares homology with cellular IRFs,
      is a multifunctional protein. To identify unknown functions of vIRF3, we
      performed luciferase-reporter assays in the presence of vIRF3. These analyses
      revealed that overexpression of vIRF3 inhibited T-cell factor (TCF)-dependent
      transcriptional activity. This TCF-dependent transcription was associated with
      the Wnt signaling pathway, which normally regulates embryonic development, but
      contributes to oncogenesis under dysregulated conditions. Using a mutagenesis
      analysis, we identified a CREB-binding protein-interaction motif (LXXLL) in vIRF3
      as an important region for its inhibitory activity. Collectively, our findings
      provide insight into the dysregulation of host signaling pathways in KSHV
      infected cells.

PMID- 27693584
TI  - Drug induced exocytosis of glycogen in Pompe disease.
AB  - Pompe disease is caused by a deficiency in the lysosomal enzyme alpha
      glucosidase, and this leads to glycogen accumulation in the autolysosomes of
      patient cells. Glycogen storage material is exocytosed at a basal rate in
      cultured Pompe cells, with one study showing up to 80% is released under specific
      culture conditions. Critically, exocytosis induction may reduce glycogen storage
      in Pompe patients, providing the basis for a therapeutic strategy whereby stored
      glycogen is redirected to an extracellular location and subsequently degraded by
      circulating amylases. The focus of the current study was to identify compounds
      capable of inducing rapid glycogen exocytosis in cultured Pompe cells. Here,
      calcimycin, lysophosphatidylcholine and alpha-l-iduronidase each significantly
      increased glycogen exocytosis compared to vehicle-treated controls. The most
      effective compound, calcimycin, induced exocytosis through a Ca2+-dependent
      mechanism, although was unable to release a pool of vesicular glycogen larger
      than the calcimycin-induced exocytic pore. There was reduced glycogen release
      from Pompe compared to unaffected cells, primarily due to increased granule size
      in Pompe cells. Drug induced exocytosis therefore shows promise as a therapeutic
      approach for Pompe patients but strategies are required to enhance the release of
      large molecular weight glycogen granules.

PMID- 27693585
TI  - Cleavage of influenza RNA by using a human PUF-based artificial RNA-binding
      protein-staphylococcal nuclease hybrid.
AB  - Various viruses infect animals and humans and cause a variety of diseases,
      including cancer. However, effective methodologies to prevent virus infection
      have not yet been established. Therefore, development of technologies to
      inactivate viruses is highly desired. We have already demonstrated that cleavage
      of a DNA virus genome was effective to prevent its replication. Here, we expanded
      this methodology to RNA viruses. In the present study, we used staphylococcal
      nuclease (SNase) instead of the PIN domain (PilT N-terminus) of human SMG6 as an
      RNA-cleavage domain and fused the SNase to a human Pumilio/fem-3 binding factor
      (PUF)-based artificial RNA-binding protein to construct an artificial RNA
      restriction enzyme with enhanced RNA-cleavage rates for influenzavirus. The
      resulting SNase-fusion nuclease cleaved influenza RNA at rates 120-fold greater
      than the corresponding PIN-fusion nuclease. The cleaving ability of the PIN
      fusion nuclease was not improved even though the linker moiety between the PUF
      and RNA-cleavage domain was changed. Gel shift assays revealed that the RNA
      binding properties of the PUF derivative used was not as good as wild type PUF.
      Improvement of the binding properties or the design method will allow the SNase
      fusion nuclease to cleave an RNA target in mammalian animal cells and/or
      organisms.

PMID- 27693586
TI  - Serum level of scorpion toxins, electrolytes and electrocardiogram alterations in
      Mexican children envenomed by scorpion sting.
AB  - The scorpion Centruroides limpidus limpidus (C.l.l.) is endemic in Mexico,
      producing hundreds of accidents in humans; children being one of the most
      susceptible targets. Few studies reported that severe envenoming by scorpion
      venom induces cardiac damage and electrolytes abnormalities in children, but the
      relationship of envenoming severity and toxic blood levels is unknown. The aim of
      this study was to determine the relationship among clinical status of envenoming,
      serum electrolyte, electrocardiographic abnormalities, and serum toxin levels in
      44 children stung by scorpion over a period of 6 months in the State of Morelos,
      Mexico. The patients were said to be asymptomatic, when they presented just local
      symptoms, and were said to be symptomatic when showing local symptoms and at
      least one systemic symptom. The clinical status was evaluated at the admission at
      the emergency room of the Hospital, and 30 min after the administration of
      polyspecific F(ab')2 anti-scorpion therapy to symptomatic children. Forty-one
      percent of the children were asymptomatic and 59% symptomatic. Potassium and
      sodium imbalance and an elongation of the QT interval were detected; the rate of
      hypokalemia was higher in symptomatic than on asymptomatic children (50% and 6%,
      respectively). Hypokalemia persisted in 19% in symptomatic patients, whereas
      sodium reached normal levels 30 min after anti-venom therapy. The hypokalemia
      statistically correlated with elongation of the QT interval. The concentration of
      the toxic components of C.l.l in serum was significantly higher in symptomatic
      than asymptomatic children, and the serum levels of the toxic component
      significantly decreased to undetectable levels after the application of anti
      venom therapy. Despite the small size of the sample, this study establishes that
      severity of envenoming was statistically related to potassium imbalance in serum,
      QT interval and the concentration of toxic components in serum, which decreased
      at undetectable levels after specific treatment with the anti-scorpion venom,
      correlating with clinical disappearance or greatly reduction of symptoms of
      envenomation.

PMID- 27693587
TI  - Attention-deficit/hyperactivity disorder and eating disorders across the
      lifespan: A systematic review of the literature.
AB  - Attention-deficit/hyperactivity disorder (ADHD) and eating disorders are common
      and concerning mental health disorders. There is both empirical and theoretical
      support for an association between ADHD and eating disorders or disordered
      eating. This systematic review aims to summarize the extant literature on the
      comorbidity of ADHD and eating disorders across the lifespan, including the
      influences of sex, age, eating disorder diagnosis, and potential mediators. A
      total of 37 peer-reviewed studies on diagnosed ADHD and eating disturbances were
      identified through key research databases. Twenty-six studies supported a strong
      empirical association between ADHD and eating disorders or disordered eating. The
      systematic review findings suggest that children with ADHD are at risk for
      disordered eating, while adolescents, emerging adults, and adults are at risk for
      both eating disorders and disordered eating. Methodological considerations,
      future research, and clinical implications are discussed.

PMID- 27693588
TI  - Genetics of human lupus nephritis.
AB  - Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease
      characterized by immune complex formation with multi-organ manifestations. Lupus
      nephritis (LN) is one of the most severe types of organ damage in SLE, and it
      clearly contributes to increased morbidity and mortality due to SLE. LN occurs
      more frequently and is more severe in non-European ancestral backgrounds,
      although the cause of this disparity remains largely unknown. Genetic factors
      play an important role in the pathogenesis of SLE. Although many SLE
      susceptibility genes have been identified, the genetic basis of LN is not as well
      understood. While some of the established general SLE susceptibility genes are
      associated with LN, recent discoveries highlight a number of genes with renal
      functions that are specifically associated with LN. Some of these genes
      associated with LN help to explain the disparity in the prevalence of nephritis
      between individuals with SLE, and also partially explain differences in LN
      between ancestral backgrounds. Moreover, not only the gene mutations, but also
      post-translational modifications seem to play important roles in the pathogenesis
      of LN. Overall it seems likely that a combination of general SLE susceptibility
      genes cooperate with LN specific risk genes to result in the genetic propensity
      for LN. In this review, we will outline the genetic contribution to LN and
      describe possible roles of LN susceptibility genes.

PMID- 27693589
TI  - Probing phosphoethanolamine-containing lipids in membranes with
      duramycin/cinnamycin and aegerolysin proteins.
AB  - In this mini-review, we summarize current knowledge about the lipid-binding
      characteristics of two types of toxins used to visualize the membrane
      distribution of phosphoethanolamine-containing lipid species: the
      glycerophospholipid, phosphatidylethanolamine (PE) and the sphingolipid, ceramide
      phosphoethanolamine (CPE). The lantibiotic cinnamycin and the structurally
      related peptide duramycin produced by some Gram-positive bacteria were among the
      first toxins characterized by their specificity for PE which is widely present in
      animal kingdoms from bacteria to mammals. These toxins promoted their binding to
      PE-containing membranes by changing membrane curvature and by inducing
      transbilayer lipid movement. The recognition of the conical shape and negative
      curvature adopted by the PE species within the membrane, is important to
      understand how lipid-peptide interaction can occur. Three mushroom-derived
      proteins belonging to the aegerolysin family, pleurotolysin A2, ostreolysin and
      erylysin A were recently described as efficient tools to visualize the membrane
      distribution of CPE which is found in trace amounts in mammalian cells but in
      higher amounts in some developmental stages of lower eukaryotes like Trypanosoma
      and in invertebrates such as Drosophila. The recent development of lantibiotic
      based PE-specific and aegerolysin-based CPE-specific probes is useful to
      visualize and specify the role of these lipids in various pathophysiological
      events such as cell division, apoptosis, tumor vasculature and parasite
      developmental stages.

PMID- 27693590
TI  - Food as a supplementary cue triggers seasonal changes in aggression, but not
      reproduction, in Siberian hamsters.
AB  - Animals living in temperate regions prepare for harsh winter conditions by
      responding to environmental cues that signal resource availability (e.g., food,
      day length). Siberian hamsters (Phodopus sungorus) breed in long, summer-like
      days (LD, >14h light), i.e., photoperiods, and undergo robust gonadal regression
      and become more aggressive when exposed to short, winter-like photoperiods that
      signal impending limited resources (SD, <10h light). When hamsters are reared
      within an intermediate photoperiod (ID, 13.5h light), they are reproductively
      active, but undergo gonadal regression in response to mild food restriction (FR)
      over 6-12weeks. We hypothesized that short-term (1-2weeks) FR in an ID
      photoperiod would provide a signal of impending limited resources and initiate
      the seasonal increase in aggression typical of SD photoperiods, as well as alter
      reproductive behaviors in advance of gonadal regression. To test this, we housed
      male and female hamsters in LD or ID photoperiods, with ad libitum (AL) access to
      food or a 90%-AL ration. We tested aggressive behavior after one week and
      reproductive behavior after two weeks, and subsequently monitored females for
      pregnancy and litter production. Both sexes displayed increased aggression in the
      ID-FR treatment. Untreated male intruders were less likely to ejaculate when
      paired with ID females during reproductive encounters. ID-FR males were
      undergoing gonadal regression after two weeks, but were more likely to have
      ejaculated. Female pregnancy and litter characteristics were unaltered by
      treatment: females were equally likely to achieve pregnancy and produce
      comparable litters across treatment groups. Collectively, we demonstrate that a
      signal of diminishing resources in an ID photoperiod is sufficient to trigger
      seasonal aggression, but that hamsters are reproductively resilient to inhibitory
      environmental cues in the short term. Broadly, our findings provide an important
      context for exploring seasonal changes in behavior and physiology from an
      ultimate perspective.

PMID- 27693592
TI  - Heart rate variability during sleep in children with autism spectrum disorders.

PMID- 27693591
TI  - Ovariectomy results in inbred strain-specific increases in anxiety-like behavior
      in mice.
AB  - Women are at an increased risk for developing affective disorders during times of
      hormonal flux, including menopause when the ovaries cease production of estrogen.
      However, while all women undergo menopause, not all develop an affective
      disorder. Increased vulnerability can result from genetic predisposition,
      environmental factors and gene by environment interactions. In order to
      investigate interactions between genetic background and estrogen depletion, we
      performed bilateral ovariectomy, a surgical procedure that results in estrogen
      depletion and is thought to model the post-menopausal state, in a genetically
      defined panel of 37 inbred mouse strains. Seventeen days post-ovariectomy, we
      assessed behavior in two standard rodent assays of anxiety- and depressive-like
      behavior, the open field and forced swim tests. We detected a significant
      interaction between ovariectomy and genetic background on anxiety-like behavior
      in the open field. No strain specific effects of ovariectomy were observed in the
      forced swim assay. However, we did observe significant strain effects for all
      behaviors in both the open field and forced swim tests. This study is the largest
      to date to look at the effects of ovariectomy on behavior and provides evidence
      that ovariectomy interacts with genetic background to alter anxiety-like behavior
      in an animal model of menopause.

PMID- 27693593
TI  - The contribution of trait negative affect and stress to recall for bodily states.
AB  - How does trait negative affect shape somatic memory of stressful events? We
      hypothesized that negative affect would impair accurate recall of one's own heart
      rate during stressful situations. Two bio-behavioral studies used a new paradigm
      to test retrospective visceral perception and assessed whether negative affective
      states experienced during aversive events (i.e., the Trier Stress Task-Time 1)
      would retrospectively shape recall of past heart rate (Time 2), even when
      accounting for actual heart rate at the time of each stressful event (Time 1).
      Results across both studies showed that individual differences in negative affect
      in response to a stressful task predicted visceral recollections, and those who
      experienced more negative affect were more inaccurate. Negative affect was
      associated with a tendency to remember visceral reactions as worse than they
      actually were.

PMID- 27693595
TI  - Biomarker Development in COPD: Moving From P Values to Products to Impact Patient
      Care.
AB  - There is a great interest in developing biomarkers to enable precision medicine
      and improve health outcomes of patients with COPD. However, biomarker development
      is extremely challenging and expensive, and translation of research endeavors to
      date has been largely unsuccessful. In most cases, biomarkers fail because of
      poor replication of initial promising results in independent cohorts and/or
      inability to transfer the biomarker from a discovery platform to a clinical
      assay. Ultimately, new biomarker assays must address 5 questions for optimal
      clinical translation. They include the following: is the biomarker likely to be
      (1) superior (will the test outperform current standards?); (2) actionable (will
      the test change patient management?); (3) valuable (will the test improve patient
      outcomes?); (4) economical (will the implementation of the biomarker in the
      target population be cost-saving or cost-effective?); and (5) clinically
      deployable (is there a pathway for the biomarker and analytical technology to be
      implemented in a clinical laboratory?)? In this article we review some of the
      major barriers to biomarker development in COPD and provide possible solutions to
      overcome these limitations, enabling translation of promising biomarkers from
      discovery experiments to clinical implementation.

PMID- 27693596
TI  - Variation of Ciliary Beat Pattern in Three Different Beating Planes in Healthy
      Subjects.
AB  - BACKGROUND: Digital high-speed video microscopy (DHSV) allows analysis of ciliary
      beat frequency (CBF) and ciliary beat pattern (CBP) of respiratory cilia in three
      planes. Normal reference data use a sideways edge to evaluate ciliary dyskinesia
      and calculate CBF using the time needed for a cilium to complete 10 beat cycles.
      Variability in CBF within the respiratory epithelium has been described, but data
      concerning variation of CBP is limited in healthy epithelium. This study aimed to
      document variability of CBP in normal samples, to compare ciliary function in
      three profiles, and to compare CBF calculated over five or 10 beat cycles.
      METHODS: Nasal brushing samples from 13 healthy subjects were recorded using DHSV
      in three profiles. CBP and CBF over a 10-beat cycle were evaluated in all
      profiles, and CBF was reevaluated over five-beat cycles in the sideways edges.
      RESULTS: A uniform CBP was seen in 82.1% of edges. In the sideways profile,
      uniformity within the edge was lower (uniform normal CBP, 69.1% [sideways
      profile]; 97.1% [toward the observer], 92.0% [from above]), and dyskinesia was
      higher. Interobserver agreement for dyskinesia was poor. CBF was not different
      between profiles (P = .8097) or between 10 and five beat cycles (P = .1126).
      CONCLUSIONS: Our study demonstrates a lack of uniformity and consistency in
      manual CBP analysis of samples from healthy subjects, emphasizing the risk of
      automated CBP analysis in limited regions of interest and of single and limited
      manual CBP analysis. The toward the observer and from above profiles may be used
      to calculate CBF but may be less sensitive for evaluation of ciliary dyskinesia
      and CBP. CBF can be measured reliably by evaluation of only five-beat cycles.

PMID- 27693594
TI  - OSA and Cardiac Arrhythmogenesis: Mechanistic Insights.
AB  - A surge of data has reproducibly identified strong associations of OSA with
      cardiac arrhythmias. As an extension of epidemiologic and clinic-based findings,
      experimental investigations have made strides in advancing our understanding of
      the putative OSA and cardiac arrhythmogenesis mechanistic underpinnings. Although
      most studies have focused on the links between OSA and atrial fibrillation (AF),
      relationships with ventricular arrhythmias have also been characterized. Key
      findings implicate OSA-related autonomic nervous system fluctuations typified by
      enhanced parasympathetic activation during respiratory events and sympathetic
      surges subsequent to respiratory events, which contribute to augmented arrhythmic
      propensity. Other more immediate pathophysiologic influences of OSA-enhancing
      arrhythmogenesis include intermittent hypoxia, intrathoracic pressure swings
      leading to atrial stretch, and hypercapnia. Intermediate pathways by which OSA
      may trigger arrhythmia include increased systemic inflammation, oxidative stress,
      enhanced prothrombotic state, and vascular dysfunction. Long-term OSA-associated
      sequelae such as hypertension, atrial enlargement and fibrosis, ventricular
      hypertrophy, and coronary artery disease also predispose to cardiac arrhythmia.
      These factors can lead to a reduction in atrial effective refractory period,
      triggered and abnormal automaticity, and promote slowed and heterogeneous
      conduction; all of these mechanisms increase the persistence of reentrant
      arrhythmias and prolong the QT interval. Cardiac electrical and structural
      remodeling observed in OSA animal models can progress the arrhythmogenic
      substrate to further enhance arrhythmia generation. Future investigations
      clarifying the contribution of specific OSA-related mechanistic pathways to
      arrhythmia generation may allow targeted preventative therapies to mitigate OSA
      induced arrhythmogenicity. Furthermore, interventional studies are needed to
      clarify the impact of OSA pathophysiology reversal on cardiac arrhythmogenesis
      and related adverse outcomes.

PMID- 27693597
TI  - A Subnational Analysis of Mortality and Prevalence of COPD in China From 1990 to
      2013: Findings From the Global Burden of Disease Study 2013.
AB  - BACKGROUND: The trends of COPD mortality and prevalence over the past 2 decades
      across all provinces remain unknown in China. We used data from the Global Burden
      of Disease Study 2013 (GBD 2013) to estimate the mortality and prevalence of COPD
      during 1990 to 2013 at a provincial level. METHODS: Following the general
      analytic strategy used in GBD 2013, we analyzed the age- sex- and province
      specific mortality and prevalence of COPD in China. Levels of and trends in COPD
      mortality and prevalence were assessed for 33 province-level administrative units
      during 1990 to 2013. RESULTS: In 2013, there were 910,809 deaths from COPD in
      China, accounting for 31.1% of the total deaths from COPD in the world. From 1990
      to 2013, the age-standardized COPD mortality rate decreased in all provinces,
      with the highest reduction in Heilongjiang (70.2%) and Jilin (70.0%) and the
      lowest reduction in Guizhou (26.8%). In 2013, the death rate per 100,000 was
      highest in Guizhou (196.0) and lowest in Tianjin (34.0) among men and highest in
      Gansu (141.1) and lowest in Beijing (23.7) among women. The number of COPD cases
      increased dramatically from 32.4 million in 1990 to 54.8 million in 2013. The age
      standardized prevalence rate of COPD remained stable overall and varied little
      for all provinces. CONCLUSIONS: COPD remains a huge health burden in many western
      provinces in China. The substantial increase in COPD cases represents an ongoing
      challenge given the rapidly aging Chinese population. A targeted control and
      prevention strategy should be developed at a provincial level to reduce the
      burden caused by COPD.

PMID- 27693598
TI  - Impact of cerium oxide nanoparticles shape on their in vitro cellular toxicity.
AB  - Cerium oxides (CeO2) nanoparticles, also referred to as nanoceria, are
      extensively used with a wide range of applications. However, their impact on
      human health and on the environment is not fully elucidated. The aim of this
      study was to investigate the influence of the CeO2 nanoparticles morphology on
      their in vitro toxicity. CeO2 nanoparticles of similar chemical composition and
      crystallinity were synthesized, only the shape varied (rods or
      octahedrons/cubes). Macrophages from the RAW264.7 cell line were exposed to these
      different samples and the toxicity was evaluated in terms of lactate
      dehydrogenase (LDH) release, Tumor Necrosis Factor alpha (TNF-alpha) production
      and reactive oxygen species (ROS) generation. Results showed no ROS production,
      whatever the nanoparticle shape. The LDH release and the TNF-alpha production
      were significantly and dose-dependently enhanced by rod-like nanoparticles,
      whereas they did not vary with cubic/octahedral nanoparticles. In conclusion, a
      strong impact of CeO2 nanoparticle morphology on their in vitro toxicity was
      clearly demonstrated, underscoring that nanoceria shape should be carefully taken
      in consideration, especially in a "safer by design" context.

PMID- 27693599
TI  - Pleiotropic properties of ASK1.
AB  - BACKGROUND: Apoptosis signal-regulating kinase 1 (ASK1), also known as mitogen
      activated protein kinase kinase kinase 5 (MAP3K5), has the potential to induce
      cellular apoptosis under various physiological conditions. It has long been
      suggested that ASK1 is highly sensitive to oxidative stress and contributes
      substantially to apoptosis. However, recent studies have indicated that ASK1 has
      pleiotropic roles in living organisms through other mechanisms in addition to
      apoptosis. SCOPE OF THE REVIEW: This review describes the physiological functions
      of ASK1 in living organisms, focusing on the regulatory mechanisms of ASK1
      activity and its importance in the pathogenesis of various diseases. We also
      highlight recent works published within the past few years. MAJOR CONCLUSIONS:
      ASK1 forms a high-molecular-mass complex within the cell, designated as the ASK1
      signalosome. Soon after the discovery of ASK1, several regulatory components of
      the ASK1 signalosome have been revealed, including thioredoxin (Trx), tumor
      necrosis factor alpha receptor-associated factors (TRAFs) and 14-3-3s. In
      parallel with the precise analyses unveiling the molecular basis of ASK1
      regulation, the physiological or pathophysiological significance of ASK1 in
      diverse organs has been elucidated. In addition to the generation of global
      knockout mice or tissue-specific knockout mice, ASK1-specific inhibitors have
      illuminated the biological roles of ASK1. GENERAL SIGNIFICANCE: The multi-faceted
      features of the function of ASK1 have been discovered over the past two decades,
      revealing that ASK1 is a crucial molecule for maintaining cellular homeostasis,
      especially under conditions of stress. Based on the results that ASK1 deficiency
      provides beneficial effects for several diseases, modulating ASK1 activity is a
      promising method to ameliorate a subset of diseases.

PMID- 27693600
TI  - Nonlinear coda wave interferometry for the global evaluation of damage levels in
      complex solids.
AB  - A nonlinear acoustic method to assess the damage level of a complex medium is
      discussed herein. Thanks to the highly nonlinear elastic signatures of cracks or,
      more generally, internal solid contacts, this method is able to distinguish
      between contributions from linear wave scattering by a heterogeneity and
      contributions from nonlinear scattering by a crack or unbounded interface. The
      coda wave interferometry (CWI) technique is applied to reverberated and scattered
      waves in glass plate samples featuring various levels of damage. The ultrasonic
      coda signals are recorded in both the absence and presence of an independent and
      lower-frequency elastic "pump" wave, before being analyzed by CWI. The monitored
      CWI parameters quantifying changes in these coda signals, which therefore
      quantify the nonlinear wave-mixing effects between the coda and pump waves, are
      found to be dependent on the damage level in the sample. A parametric study is
      also performed to analyze the influence of sensor positions and average
      temperature on the method's output. The reported results could be applied to the
      non-destructive testing and evaluation of complex-shape materials and multiple
      scattering samples, for which conventional ultrasonic methods show strong
      limitations.

PMID- 27693601
TI  - Lung surfactant: Function and composition in the context of development and
      respiratory physiology.
AB  - Lung surfactant is a complex with a unique phospholipid and protein composition.
      Its specific function is to reduce surface tension at the pulmonary air-liquid
      interface. The underlying Young-Laplace equation, applying to the surface of any
      geometrical structure, is the more important the smaller its radii are. It
      therefore applies to the alveoli and bronchioli of mature lungs, as well as to
      the tubules and saccules of immature lungs. Surfactant comprises 80%
      phosphatidylcholine (PC), of which dipalmitoyl-PC, palmitoyl-myristoyl-PC and
      palmitoyl-palmitoleoyl-PC together are 75%. Anionic phosphatidylglycerol and
      cholesterol are about 10% each, whereas surfactant proteins SP-A to -D comprise 2
      5%. Maturation of the surfactant system is not essentially due to increased
      synthesis but to decreased turnover of specific components. Molecular differences
      correlate with resting respiratory rate (RR), where PC16:0/16:0 is the lower the
      higher RR is. PC16:0/14:0 is increased during alveolar formation, and decreases
      immune reactions that might impair alveolar development. In rigid bird lungs,
      with air-capillaries rather than alveoli, and no surface area changes during the
      respiratory cycle, PC16:0/16:0 is highest and PC16:0/14:0 absent. As there is no
      need for a surface-associated surfactant reservoir, SP-C is absent in birds as
      well. Airflow is lowest and particle sedimentation highest in the extrapulmonary
      air-sacs, rather than in the gas-exchange area. Consequently, SP-A and -D for
      particle opsonization are absent in bird surfactant. In essence, comparative
      analysis is consistent with the concept that surfactant is adapted to the
      physiologic needs of a given vertebrate species at a given developmental stage.

PMID- 27693602
TI  - Fetal development of the pulley for muscle insertion tendons: A review and new
      findings related to the tensor tympani tendon.
AB  - The existence of hard tissue pulleys that act to change the direction of a muscle
      insertion tendon is well known in the human body. These include (1) the trochlea
      for the extraocular obliquus superior muscle, (2) the pterygoid hamulus for the
      tensor veli palatini muscle, (3) the deep sulcus on the plantar aspect of the
      cuboid bone for the peroneus longus tendon, (4) the lesser sciatic notch for the
      obturator internus muscle, and (5) the bony trochleariformis process for the
      tensor tympani muscle tendon. In addition, (6) the stapedius muscle tendon shows
      a lesser or greater angulation at the pyramidal eminence of the temporal bone.
      Our recent studies have shown that the development of pulleys Nos. 1 and 2 can be
      explained by a change in the topographical relationship between the pulley and
      the tendon, that of pulley No. 3 by the rapidly growing calcaneus pushing the
      tendon, and that of pulley No. 4 by migration of the insertion along the sciatic
      nerve and gluteus medius tendon. Therefore, in Nos. 1-4, an initially direct
      tendon curves secondarily and obtains an attachment to the pulley. In case No. 6,
      the terminal part of the stapedius tendon originates secondarily from the
      interzone mesenchymal tissue of the incudostapedial joint. In the case of pulley
      No. 5, we newly demonstrated that its initial phase of development was similar to
      No. 6, but the tensor tympani tendon achieved a right-angled turn under guidance
      by a specific fibrous tissue and it migrated along the growing malleus manubrium.

PMID- 27693603
TI  - Analysis of amino acids in human blood using UHPLC-MS/MS: Potential interferences
      of storage time and vacutainer tube in pre-analytical procedure.
AB  - OBJECTIVES: To investigate potential interferences of two pre-analytical
      variables, the storage time and the vacutainer tube, on the quantification of 20
      amino acids using a UHPLC-MS/MS method. DESIGN AND METHODS: Blood samples from 25
      apparently healthy subjects were collected into duplicate sets of EDTA-2K, EDTA
      3K, coagulation, heparin and citrate tubes, and stored in capped vacutainer tubes
      at 4 degrees C for 6h, 12h and 24h before sample analysis. A UHPLC-MS/MS method
      was established for simultaneous quantification of 20 amino acids. ANOVA for
      repeated measurement was conducted based on the model of Mauchly's test of
      Sphericity. Student's t-test was applied for comparison between amino acid
      concentrations obtained from different vacutainer tubes, and consistency of the
      results was checked through Bland-Altman difference plots and Passing-Bablok
      regression analysis. RESULTS: Most of the 20 amino acids showed a least
      concentration fluctuation with storage time in heparin plasma, followed by EDTA
      3K and citrate plasma. The amino acid concentrations were significantly lower in
      citrate plasma and slightly higher in serum, compared with those in heparin
      plasma. No fixed bias was observed for amino acid concentrations in EDTA and
      heparin plasma, but the differences were mostly of statistical significance.
      Amino acid concentrations in EDTA-3K plasma achieved a good consistency with
      those in heparin plasma by UHPLC-MS/MS analysis. CONCLUSIONS: Storage time and
      vacutainer tube were important variables for amino acid analysis. They should
      draw researchers' attention and then be controlled in good laboratory practice to
      reduce pre-analytical errors.

PMID- 27693604
TI  - Anaerobic digestion of straw and corn stover: The effect of biological process
      optimization and pre-treatment on total bio-methane yield and energy performance.
AB  - Anaerobic digestion (AD) is a useful method for producing renewable
      energy/biofuel. Today, biogas production uses a large amount of energy crops
      (EC), with the effect of increasing AD costs and creating conflict between
      food/feed vs. energy use. A partial solution to this might be the substitution of
      EC with agricultural wastes, e.g. straw. Straw and corn stover are widely
      available in the world and approximately 1600millionMgyear-1 of these substrates
      are available. Straw can be useful used for biogas production but its
      characteristics limit its performance so that sometimes the energetic balance can
      be negative. In this review, the limits for the conversion of this substrate into
      biogas were investigated and solutions/proposals for getting higher straw biogas
      production performance are reported. In addition, energetic balances for
      untreated and pre-treated substrates are reported, giving indicative evaluations
      of the sustainability of straw and corn stover use for biogas production.

PMID- 27693605
TI  - The Prognostic Significance of Different Definitions for Angiosome-Targeted Lower
      Limb Revascularization.
AB  - BACKGROUND: The definition of angiosome-targeted revascularization is confusing,
      especially when a tissue lesion affects several angiosomes. Two different
      definitions of direct revascularization exist in the literature. The study aim
      was (1) to compare the 2 definitions of direct revascularization in patients with
      foot lesions involving more than one angiosome and (2) to evaluate which
      definition better predicts clinical outcome. METHODS: This study cohort comprises
      658 patients with Rutherford 5-6 foot lesions who underwent infrapopliteal
      endovascular or surgical revascularization between January 2010 and July 2013. We
      compared the 2 angiosome-targeted definitions using multivariate analysis; the
      impact of each angiosome-targeted definition was adjusted for a propensity score
      obtained by means of nonparsimonious logistic regression. RESULTS: Direct
      revascularization according to definition A was performed in 367 cases (55.8%)
      versus 198 cases (30.1%) with definition B. The propensity-score-adjusted
      analysis showed that definition A of direct revascularization was associated with
      significantly better wound healing (P < 0.044, hazard ratio [HR] 1.291) and lower
      amputation rates (P < 0.047, HR 0.706), whereas definition B was associated only
      with significantly better wound healing (P < 0.029, HR 1.321). The prognostic
      ability of direct revascularization according to definition A was confirmed in a
      Cox proportional hazard analysis. CONCLUSIONS: Definition A of direct
      revascularization was associated with a significantly higher wound healing and
      leg salvage rate than indirect revascularization in both series. Therefore, it
      seems that, if the wound spreads over several angiosomes in the forefoot or heel,
      any angiosome involved in the wound can be targeted.

PMID- 27693606
TI  - Technical aspects of MRI signal change quantification after gadolinium-based
      contrast agents' administration.
AB  - Over the last 2years several studies have been published regarding gadolinium
      deposition in brain structures in patients with normal renal function after
      repeated administrations of gadolinium-based contrast agents (GBCAs). Most of the
      publications are magnetic resonance imaging (MRI) based retrospective studies,
      where gadolinium deposition may be indirectly measured by evaluating changes in
      T1 signal intensity (SI) in brain tissue, particularly in the dentate nucleus
      (DN) and/or globus pallidi (GP). The direct correlation between T1 signal changes
      and gadolinium deposition was validated by human pathology studies. However, the
      variability of the MR equipment and parameters used across different
      publications, along with the inherent limitations of MRI to assess gadolinium in
      human tissues should be acknowledged when interpreting those studies.
      Nevertheless, MRI studies remain essential regarding gadolinium bio-distribution
      knowledge. The aim of this paper is to overview current knowledge of technical
      aspects of T1 signal intensity evaluation by MRI and describe confounding
      factors, with the intention to achieve higher accuracy and maximize
      reproducibility.

PMID- 27693607
TI  - Gadolinium toxicity and treatment.
AB  - Gadolinium based contrast agents (GBCAs) play an important role in the diagnostic
      evaluation of many patients. The safety of these agents has been once again
      questioned after gadolinium deposits were observed and measured in brain and bone
      of patients with normal renal function. This retention of gadolinium in the human
      body has been termed "gadolinium storage condition". The long-term and cumulative
      effects of retained gadolinium in the brain and elsewhere are not as yet
      understood. Recently, patients who report that they suffer from chronic symptoms
      secondary to gadolinium exposure and retention created gadolinium-toxicity on
      line support groups. Their self-reported symptoms have recently been published.
      Bone and joint complaints, and skin changes were two of the most common
      complaints. This condition has been termed "gadolinium deposition disease". In
      this review we will address gadolinium toxicity disorders, from acute adverse
      reactions to GBCAs to gadolinium deposition disease, with special emphasis on the
      latter, as it is the most recently described and least known.

PMID- 27693609
TI  - Neural oscillations as a bridge between glutamatergic system and emotional
      behaviors in simulated microgravity-induced mice.
AB  - This study aims to investigate if neural oscillations can play a role as a bridge
      between the alteration of glutamatergic system and emotional behaviors in
      simulated microgravity (SM) mice. Adult male C57BL/6J mice were randomly divided
      into two groups: SM and control groups. The animal model was established by
      hindlimb unloading (HU). The mice were exposed to HU continued for 14days. Weight
      and sucrose consumption were measured. The degree of anxious and depressive was
      evaluated by Open field test and Elevated plus maze test. Local field potentials
      were recorded in the hippocampal perforant path (PP) and dentate gyrus (DG)
      regions. The NMDAR2A/2B (NR2A/2B) subunits expression and glutamate level were
      measured by Western and high performance liquid chromatography (HPLC),
      respectively. After 14days, SM mice exhibited depressive-like and anxiety-like
      behaviors, while the expression of NR2A/2B subunits and the glutamate level were
      significantly decreased in the SM group. Moreover, the power distribution of
      theta (3-8Hz) was decreased by HU, which further significantly attenuated the
      identical-frequency strength of phase synchronization and the neural information
      flow at theta rhythm on the PP-DG pathway. The theta-gamma phase synchronization
      strength was also significantly reduced by HU. The data imply that the neural
      oscillations measurements is a sign of the emotional behaviors impairment and the
      glutamatergic system change induced by HU.

PMID- 27693608
TI  - Fibroblast growth factor 2 alters the oxytocin receptor in a developmental model
      of anxiety-like behavior in male rat pups.
AB  - We aimed to determine the short-term effects of early-life stress in the form of
      maternal separation (MS) on anxiety-like behavior in male rat pups. In order to
      assess anxiety, we measured 40kHz separation-induced ultrasonic vocalizations
      (USV) on postnatal day (PND) 11. We further aimed to evaluate the potential
      involvement of two neurochemical systems known to regulate social and anxiety
      like behaviors throughout life: oxytocin (OT) and fibroblast growth factor 2
      (FGF2). For these purposes, we tested the effects of neonatal administration (on
      PND1) of an acute dose of FGF2 on USV and its potential interaction with MS. In
      addition, we validated the anxiolytic effects of OT and measured oxytocin
      receptor (OTR) gene expression, binding and epigenetic regulation via histone
      acetylation. Our results show that MS potentiated USV while acute administration
      of OT and FGF2 attenuated them. Further, we found that both FGF2 and MS increased
      OTR gene expression and the association of acH3K14 with the OTR promoter in the
      bed nucleus of the stria terminalis (BNST). Comparable changes, though not as
      pronounced, were also found for the central amygdala (CeA). Our findings suggest
      that FGF2 may exert its anxiolytic effects in male MS rats by a compensatory
      increase in the acetylation of the OTR promoter to overcome reduced OT levels in
      the BNST.

PMID- 27693610
TI  - Deficit in emotional learning in neurotrimin knockout mice.
AB  - Neurotrimin (Ntm) belongs to the IgLON family of cell adhesion molecules with
      Lsamp, Obcam and kilon that regulate the outgrowth of neurites mostly by forming
      heterodimers. IgLONs have been associated with psychiatric disorders,
      intelligence, body weight, heart disease and tumours. This study provides an
      initial behavioural and pharmacological characterization of the phenotype of Ntm
      deficient mice. We expected to see at least some overlap with the phenotype of
      Lsamp-deficient mice as Ntm and Lsamp are the main interaction partners in the
      IgLON family and are colocalized in some brain regions. However, Ntm-deficient
      mice displayed none of the deviations in behaviour that we have previously shown
      in Lsamp-deficient mice, but differently from Lsamp-deficient mice, had a deficit
      in emotional learning in the active avoidance task. The only overlap was
      decreased sensitivity to the locomotor stimulating effect of amphetamine in both
      knockout models. Thus, despite being interaction partners, on the behavioural
      level Lsamp seems to play a much more central role than Ntm and the roles of
      these two proteins seem to be complementary rather than overlapping.

PMID- 27693611
TI  - Data-driven identification of intensity normalization region based on
      longitudinal coherency of 18F-FDG metabolism in the healthy brain.
AB  - OBJECTIVES: In brain 18F-FDG PET data intensity normalization is usually applied
      to control for unwanted factors confounding brain metabolism. However, it can be
      difficult to determine a proper intensity normalization region as a reference for
      the identification of abnormal metabolism in diseased brains. In
      neurodegenerative disorders, differentiating disease-related changes in brain
      metabolism from age-associated natural changes remains challenging. This study
      proposes a new data-driven method to identify proper intensity normalization
      regions in order to improve separation of age-associated natural changes from
      disease related changes in brain metabolism. METHODS: 127 female and 128 male
      healthy subjects (age: 20 to 79) with brain18F-FDG PET/CT in the course of a
      whole body cancer screening were included. Brain PET images were processed using
      SPM8 and were parcellated into 116 anatomical regions according to the AAL
      template. It is assumed that normal brain 18F-FDG metabolism has longitudinal
      coherency and this coherency leads to better model fitting. The coefficient of
      determination R2 was proposed as the coherence coefficient, and the total
      coherence coefficient (overall fitting quality) was employed as an index to
      assess proper intensity normalization strategies on single subjects and age
      cohort averaged data. Age-associated longitudinal changes of normal subjects were
      derived using the identified intensity normalization method correspondingly. In
      addition, 15 subjects with clinically diagnosed Parkinson's disease were assessed
      to evaluate the clinical potential of the proposed new method. RESULTS: Intensity
      normalizations by paracentral lobule and cerebellar tonsil, both regions derived
      from the new data-driven coherency method, showed significantly better coherence
      coefficients than other intensity normalization regions, and especially better
      than the most widely used global mean normalization. Intensity normalization by
      paracentral lobule was the most consistent method within both analysis strategies
      (subject-based and age-cohort averaging). In addition, the proposed new intensity
      normalization method using the paracentral lobule generates significantly higher
      differentiation from the age-associated changes than other intensity
      normalization methods. CONCLUSION: Proper intensity normalization can enhance the
      longitudinal coherency of normal brain glucose metabolism. The paracentral lobule
      followed by the cerebellar tonsil are shown to be the two most stable intensity
      normalization regions concerning age-dependent brain metabolism. This may provide
      the potential to better differentiate disease-related changes from age-related
      changes in brain metabolism, which is of relevance in the diagnosis of
      neurodegenerative disorders.

PMID- 27693612
TI  - BrainNetCNN: Convolutional neural networks for brain networks; towards predicting
      neurodevelopment.
AB  - We propose BrainNetCNN, a convolutional neural network (CNN) framework to predict
      clinical neurodevelopmental outcomes from brain networks. In contrast to the
      spatially local convolutions done in traditional image-based CNNs, our
      BrainNetCNN is composed of novel edge-to-edge, edge-to-node and node-to-graph
      convolutional filters that leverage the topological locality of structural brain
      networks. We apply the BrainNetCNN framework to predict cognitive and motor
      developmental outcome scores from structural brain networks of infants born
      preterm. Diffusion tensor images (DTI) of preterm infants, acquired between 27
      and 46 weeks gestational age, were used to construct a dataset of structural
      brain connectivity networks. We first demonstrate the predictive capabilities of
      BrainNetCNN on synthetic phantom networks with simulated injury patterns and
      added noise. BrainNetCNN outperforms a fully connected neural-network with the
      same number of model parameters on both phantoms with focal and diffuse injury
      patterns. We then apply our method to the task of joint prediction of Bayley-III
      cognitive and motor scores, assessed at 18 months of age, adjusted for
      prematurity. We show that our BrainNetCNN framework outperforms a variety of
      other methods on the same data. Furthermore, BrainNetCNN is able to identify an
      infant's postmenstrual age to within about 2 weeks. Finally, we explore the high
      level features learned by BrainNetCNN by visualizing the importance of each
      connection in the brain with respect to predicting the outcome scores. These
      findings are then discussed in the context of the anatomy and function of the
      developing preterm infant brain.

PMID- 27693613
TI  - Denoising spinal cord fMRI data: Approaches to acquisition and analysis.
AB  - Functional magnetic resonance imaging (fMRI) of the human spinal cord is a
      difficult endeavour due to the cord's small cross-sectional diameter, signal drop
      out as well as image distortion due to magnetic field inhomogeneity, and the
      confounding influence of physiological noise from cardiac and respiratory
      sources. Nevertheless, there is great interest in spinal fMRI due to the spinal
      cord's role as the principal sensorimotor interface between the brain and the
      body and its involvement in a variety of sensory and motor pathologies. In this
      review, we give an overview of the various methods that have been used to address
      the technical challenges in spinal fMRI, with a focus on reducing the impact of
      physiological noise. We start out by describing acquisition methods that have
      been tailored to the special needs of spinal fMRI and aim to increase the signal
      to-noise ratio and reduce distortion in obtained images. Following this, we
      concentrate on image processing and analysis approaches that address the
      detrimental effects of noise. While these include variations of standard pre
      processing methods such as motion correction and spatial filtering, the main
      focus lies on denoising techniques that can be applied to task-based as well as
      resting-state data sets. We review both model-based approaches that rely on
      externally acquired respiratory and cardiac signals as well as data-driven
      approaches that estimate and correct for noise using the data themselves. We
      conclude with an outlook on techniques that have been successfully applied for
      noise reduction in brain imaging and whose use might be beneficial for fMRI of
      the human spinal cord.

PMID- 27693615
TI  - Variegated RHOA mutations in human cancers.
AB  - RHOA is one of the most extensively investigated members of the Rho GTPase family
      of proteins and has long been implicated in malignant transformation as well as
      tumor invasion and metastasis. Recently, revolutionized sequencing platforms have
      revealed frequent RHOA mutations in a wide variety of human cancers, including
      angio-immunoblastic T-cell lymphoma, adult T-cell leukemia/lymphoma, germinal
      center B-cell lymphoma, diffuse-type gastric cancer, and other solid tumors. With
      their discrete positional distributions and types of amino acid substitution
      depending on cancer type, different RHOA mutations seem to have unique functional
      and biological properties. However, their impact on the development of different
      types of tumors remains controversial. Here, we present an overview of the
      current understanding of RHOA mutations in human cancers and highlight the
      unanticipated complexity of their genetic and biological properties.

PMID- 27693616
TI  - ZIKA App - A great resource from the World Health Organization (WHO).

PMID- 27693614
TI  - Neural stress reactivity relates to smoking outcomes and differentiates between
      mindfulness and cognitive-behavioral treatments.
AB  - Stress and negative affect are known contributors to drug use and relapse, and
      several known treatments for addictions include strategies for managing them. In
      the current study, we administered a well-established stress provocation during
      functional magnetic resonance imaging (fMRI) to 23 participants who completed
      either mindfulness training (MT; N=11) or the American Lung Association's Freedom
      From Smoking (FFS; N=12), which is a cognitive-behavioral treatment (CBT) for
      smoking cessation. Across the entire sample, we found that stress reactivity in
      several brain regions including the amygdala and anterior/mid insula was related
      to reductions in smoking after treatment, as well as at 3-month post-treatment
      follow-up. Moreover, conjunction analysis revealed that these same regions also
      differentiated between treatment groups such that the MT group showed lower
      stress-reactivity compared to the FFS/CBT group. This suggests that reduction in
      stress reactivity may be one of the mechanisms that underlie the efficacy of MT
      in reducing smoking over time. The findings have important implications for our
      understanding of stress, the neural and psychological mechanisms that underlie
      mindfulness-based treatments, and for smoking cessation treatments more broadly.

PMID- 27693617
TI  - Myeloid-derived suppressor cells expressing a self-antigen ameliorate
      experimental autoimmune encephalomyelitis.
AB  - Previous work by our group showed that transferring bone marrow cells transduced
      with a self-antigen induced immune tolerance and ameliorated experimental
      autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). We also
      found that following retroviral transduction of murine bone marrow (BM) cells,
      the majority of cells generated and transduced were myeloid-derived suppressor
      cells (MDSCs). Here, we aimed to determine whether purified antigen-expressing
      MDSCs have similar therapeutic effects than those of unfractionated BM, and to
      investigate their potential mechanisms. We performed phenotypic and functional
      analyses in these cells using the same animal model, and we used purified antigen
      expressing MDSCs in preventive and therapeutic approaches. These cells exerted
      therapeutic effects similar to those of BM cells, which depended upon self
      antigen expression. The majority of monocytic (M)-MDSCs expressed the
      immunosuppressive molecule programmed death ligand-1 (PD-L1), CD80, CD86 and MHC
      class II molecules. Additionally, the animals infused with antigen-expressing
      cells exhibited lower percentages of activated T cells and higher percentages of
      B cells with a regulatory phenotype (B220+CD1dhigh CD5+) in the spleen than their
      respective controls. MDSCs expressing self-antigens, alloantigens or therapeutic
      transgenes are tolerogenic and can be exploited therapeutically in autoimmune
      diseases, transplantation and in gene therapy, respectively.

PMID- 27693620
TI  - Editorial.

PMID- 27693619
TI  - Inhibition of beta-catenin signaling by phenobarbital in hepatoma cells in vitro.
AB  - The antiepileptic drug phenobarbital (PB) exerts hepatic effect based on indirect
      activation of the constitutive androstane receptor (CAR) via inhibition of the
      epidermal growth factor receptor (EGFR) and the kinase Src. It has furthermore
      been observed that in mice PB suppresses the growth of hepatocellular carcinoma
      with overactive signaling through the oncogenic Wnt/beta-catenin pathway, thus
      suggesting an interference of PB with beta-catenin signaling. The present work
      was aimed to characterize effects of PB on beta-catenin signaling at different
      cellular levels and to elucidate molecular details of the interaction of PB and
      beta-catenin in an in vitro system of mouse hepatoma cells. PB efficiently
      inhibited signaling through beta-catenin. This phenomenon was in-depth
      characterized at the levels of beta-catenin protein accumulation and
      transcriptional activity. Mechanistic analyses revealed that the effect of PB on
      beta-catenin signaling was independent of the activation of CAR and also
      independent of the cytosolic multi-protein complex responsible for physiological
      post-translation control of the beta-catenin pathway via initiation of beta
      catenin degradation. Instead, evidence is provided that PB diminishes beta
      catenin protein production by inhibition of protein synthesis via signal
      transduction through EGFR and Src. The proposed mechanism is well in agreement
      with previously published activities of PB at the EGFR and Src-mediated
      regulation of beta-catenin mRNA translation. Inhibition of beta-catenin signaling
      by PB through the proposed mechanism might explain the inhibitory effect of PB on
      the growth of specific sub-populations of mouse liver tumors. In conclusion, the
      present data comprehensively characterize the effect of PB on beta-catenin
      signaling in mouse hepatoma cells in vitro and provides mechanistic insight into
      the molecular processes underlying the observed effect.

PMID- 27693618
TI  - Abbreviated environmental enrichment confers neurobehavioral, cognitive, and
      histological benefits in brain-injured female rats.
AB  - Environmental enrichment (EE) promotes behavioral recovery after experimental
      traumatic brain injury (TBI). However, the chronic rehabilitation provided in the
      laboratory is not analogous to the clinic where physiotherapy is typically
      limited. Moreover, females make up approximately 40% of the clinical TBI
      population, yet they are seldom studied in brain trauma. Hence, the goal of this
      study was to test the hypothesis that abbreviated EE would confer
      neurobehavioral, cognitive, and histological benefits in brain injured female
      rats. Anesthetized rats received a cortical impact of moderate-to-severe injury
      (2.8mm tissue deformation at 4m/s) or sham surgery and then were randomly
      assigned to groups receiving standard (STD) housing or 4h, 6h, or 24h of EE
      daily. Motor function (beam-balance/walk and rotarod) was assessed on post
      operative days 1-5 and every other day from 1 to 19, respectively. Spatial
      learning/memory (Morris water maze) was evaluated on days 14-19, and cortical
      lesion volume was quantified on day 21. No statistical differences were
      appreciated among the sham controls in any assessment and thus the data were
      pooled. All EE conditions improved motor function and memory retention, but only
      6h and 24h enhanced spatial learning relative to STD (p<0.05). Moreover, EE,
      regardless of duration reduced cortical lesion volume (p<0.05). These data
      confirm that abbreviated EE confers robust neurobehavioral, cognitive, and
      histological benefits in TBI female rats, which supports the hypothesis and
      strengthens the utility of EE as a pre-clinical model of neurorehabilitation.

PMID- 27693621
TI  - Purification, characterization and the use of recombinant prolyl oligopeptidase
      from Myxococcus xanthus for gluten hydrolysis.
AB  - Prolyl oligopeptidase (POP, EC 3.4.21.26) is a cytosolic serine protease that
      hydrolyses proline containing small peptides. The members of prolyl
      oligopeptidase family play important roles in many physiological processes such
      as neurodegenerative diseases, maturation and degradation of peptide hormones.
      Thus the enzyme has been purified and characterized from various sources to
      elucidate the potential use as therapeutics. In this study recombinant Myxococcus
      xanthus prolyl oligopeptidase expressed in E. coli was purified 60.3 fold, using
      metal-chelate affinity and gel permeation chromatography. The recombinant enzyme
      had a monomeric molecular weight of 70 kDa. Isoelectric point of the enzyme was
      found to be approximately 6.3 by two-dimensional polyacrylamide gel
      electrophoresis. The optimum pH and temperature was estimated as 7.5 and 37 
      degrees C, respectively. The purified enzyme was stable in a pH range of 6.0-8.5
      and thermally stable up to 37  degrees C. The Km and Vmax values were 0.2 mM and
      3.42 MUmol/min/mg. The proteolytic activity was inhibited by active-site
      inhibitors of serine protease, Z-Pro-Prolinal, PMSF, and metal ions, Cd2+, and
      Hg2+. Furthermore, the hydrolysis efficiency of the recombinant prolyl
      oligopeptidase was investigated with wheat gluten.

PMID- 27693622
TI  - Biosynthesis, purification and characterization of beta-1,4-xylanase from a novel
      mangrove associated actinobacterium Streptomyces olivaceus (MSU3) and its
      applications.
AB  - The present study was undertaken to evaluate the xylanolytic properties of an
      actinobacterium Streptomyces olivaceus (MSU3) isolated from the sediment sample
      of mangrove environment. It showed highest xylanase activity on initial screening
      in Breg's mineral salts medium supplemented with 0.5% xylan. Further the organism
      expressed maximum xylanase production at optimized culture conditions of pH 7,
      temperature 30  degrees C with 2.5% of inoculum size at 72 h of incubation, the
      nutrient sources like sucrose (2%) and yeast extract (3%) have observed as best
      carbon and nitrogen sources respectively. In purification, the xylanase resulted
      4.27fold increase with the yield of 15.57% at the final step using sephadex G-75
      chromatography. The molecular weight of the purified xylanase was observed as 42
      kDa on 10% SDS-PAGE and further identified by MALDI-TOF-MS analysis. It belongs
      to GH43 family encoded 485 amino acid residues and the xylanase gene isolated
      using PCR amplification was partially sequenced. It showed 98% sequence
      similarity to the xylanase gene of S. olivaceus. The maximum activity of purified
      xylanase was observed at pH 8, temperature 40  degrees C and also the production
      medium substituted with Fe3+ metal ion, 2.0% xylan and 1.5% NaCl along with Km
      and Vmax values of 8.16 mg/ml and 250.01 MUg/min/mg, respectively. In xylanolytic
      hydrolysis of pretreated agro-wastes, especially the sugarcane juice substituted
      medium yielded maximum (52.19%) reducing sugar, followed by bioethanol production
      (4.19  g/L) at 72 h of incubation. Based on the results, it could be confirmed
      that the selected isolate is a potent strain and it can able to produce xylanase
      through fermentation process and also it can able to convert the pretreated agro
      wastes into economically important byproduct like bioethanol.

PMID- 27693623
TI  - Characterization of NoV P particle-based chimeric protein vaccines developed from
      two different expression systems.
AB  - The Norovirus (NoV) P domain, with three surface loops for foreign antigen
      insertion, has been demonstrated as an excellent platform for antigen
      presentation and novel vaccine development. The P domain alone can self-assemble
      into a P dimer, 12-mer small particle or 24-mer P particle, and vaccines based on
      those particles may elicit different levels of immunogenicity. Currently, P
      particles are generally produced in soluble expression systems in Escherichia
      coli, mainly in the 24-mer form. However, the low yield of the soluble protein
      has hindered further clinical applications of P particle-based protein vaccines.
      In this study, we inserted the Alzheimer's disease (AD) immunogen Abeta1-6 into
      the three loops of the P particle to generate an AD protein vaccine. To increase
      the yield of this chimeric protein, we tested the generation of proteins in a
      soluble expression system and an inclusion body expression system separately in
      E. coli. The result showed that the inclusion body expression system could
      greatly enhance the product yield of the chimeric protein compared with the
      soluble expression system. The refolded protein from the inclusion bodies was
      mainly in the 12-mer form, while the protein generated from the soluble
      supernatant was mainly in the 24-mer form. Moreover, the immunogenicity of
      soluble proteins was significantly stronger than that of the refolded proteins.
      Thus, comparisons between the two expression methods suggested that the soluble
      expression system generated chimeric P particles with better immunogenicity,
      while inclusion body expression system yielded more P particle proteins.

PMID- 27693625
TI  - A neural mechanism of dynamic gating of task-relevant information by top-down
      influence in primary visual cortex.
AB  - Visual recognition involves bidirectional information flow, which consists of
      bottom-up information coding from retina and top-down information coding from
      higher visual areas. Recent studies have demonstrated the involvement of early
      visual areas such as primary visual area (V1) in recognition and memory
      formation. V1 neurons are not passive transformers of sensory inputs but work as
      adaptive processor, changing their function according to behavioral context. Top
      down signals affect tuning property of V1 neurons and contribute to the gating of
      sensory information relevant to behavior. However, little is known about the
      neuronal mechanism underlying the gating of task-relevant information in V1. To
      address this issue, we focus on task-dependent tuning modulations of V1 neurons
      in two tasks of perceptual learning. We develop a model of the V1, which receives
      feedforward input from lateral geniculate nucleus and top-down input from a
      higher visual area. We show here that the change in a balance between excitation
      and inhibition in V1 connectivity is necessary for gating task-relevant
      information in V1. The balance change well accounts for the modulations of tuning
      characteristic and temporal properties of V1 neuronal responses. We also show
      that the balance change of V1 connectivity is shaped by top-down signals with
      temporal correlations reflecting the perceptual strategies of the two tasks. We
      propose a learning mechanism by which synaptic balance is modulated. To conclude,
      top-down signal changes the synaptic balance between excitation and inhibition in
      V1 connectivity, enabling early visual area such as V1 to gate context-dependent
      information under multiple task performances.

PMID- 27693624
TI  - Secretory expression of bovine herpesvirus type 1/5 glycoprotein E in Pichia
      pastoris for the differential diagnosis of vaccinated or infected cattle.
AB  - Bovine herpesvirus (BoHV) glycoprotein E (gE) is a non-essential envelope
      glycoprotein and the deletion of gE has been used to develop BoHV-1 and BoHV-5
      differential vaccine strains. The DIVA (Differentiation of Infected from
      Vaccinated Animals) strategy, using marker vaccines based on gE-negative BoHV
      strains, allows the identification of vaccinated or infected animals in
      immunoassays designed to detect anti-gE antibodies. In this study a codon
      optimized synthetic sequence of gE containing highly conserved regions from BoHV
      1 and BoHV-5 was expressed in Pichia pastoris. Following expression, the
      recombinant gE (rgE) was secreted and purified from the culture medium. The rgE
      was identified by Western blotting (WB) using sera from cattle naturally infected
      with BoHV-1 and/or BoHV-5, or sera from bovines experimentally infected with wild
      type BoHV-5. Sera collected from cattle vaccinated with a BoHV-5 gI/gE/US9-
      marker vaccine failed to recognise rgE. Expression of rgE, based on a sequence
      containing highly conserved regions from BoHV-1 and BoHV-5, in P. pastoris
      enabled the production of large quantities of rgE suitable for use in
      immunoassays for the differentiation vaccinated or infected cattle.

PMID- 27693626
TI  - A general resolution of intractable problems in polynomial time through DNA
      Computing.
AB  - Based on a set of known biological operations, a general resolution of
      intractable problems in polynomial time through DNA Computing is presented. This
      scheme has been applied to solve two NP-Hard problems (Minimization of Open
      Stacks Problem and Matrix Bandwidth Minimization Problem) and three co-NP
      Complete problems (associated with Hamiltonian Path, Traveling Salesman and
      Hamiltonian Circuit), which have not been solved with this model. Conclusions and
      open questions concerning the computational capacity of this model are presented,
      and research topics are suggested.

PMID- 27693627
TI  - Effects of fasting and refeeding on gene expression of slc15a1a, a gene encoding
      an oligopeptide transporter (PepT1), in the intestine of Mozambique tilapia.
AB  - The tissue distribution of slc15a1a, a gene that encodes an oligopeptide
      transporter, PepT1, and its response to fasting and refeeding were investigated
      in the intestinal epithelium of Mozambique tilapia for a better understanding of
      its role on nutrient absorption. The slc15a1a was predominantly expressed in the
      absorptive epithelia of the anterior part of the intestine, suggesting that
      digested oligopeptides are primarily absorbed in the anterior intestine. The
      response of slc15a1a to fasting was evaluated at 1, 2, 4, 7 and 14days after the
      last feeding. Fasting revealed a biphasic effect, where short-term fasting
      significantly upregulated slc15a1a expression and long-term fasting resulted in
      downregulation. The expression level continued to decrease and fell below the pre
      fasted level from day 4 to 14. Proximal (the hepatic loop, HL) and distal parts
      (the proximal major coil, PMC) of the anterior intestine showed different
      magnitudes of responses to fasting; slc15a1a expression in the PMC showed greater
      upregulation and downregulation than that in the HL. Refeeding significantly
      stimulated slc15a1a expression at day 3, although the expression did not exceed
      the pre-fasted level. Observed responses of slc15a1a to fasting and refeeding
      suggest that the expression level of this gene can serve as a sensitive indicator
      of the changes that may occur in altering nutritional conditions. These findings
      contribute to a better understanding of the role of PepT1 in nutrition and of the
      complex mechanisms underlying the absorption of oligopeptides and amino acids in
      the intestine, and may lead to development of possible means to manipulate the
      absorption processes for the improvement of growth and other metabolic and
      physiological conditions in fish.

PMID- 27693628
TI  - Molecular and functional characterization of a fads2 orthologue in the Amazonian
      teleost, Arapaima gigas.
AB  - The Brazilian teleost Arapaima gigas is an iconic species of the Amazon. In
      recent years a significant effort has been put into the farming of arapaima to
      mitigate overfishing threats. However, little is known regarding the nutritional
      requirements of A. gigas in particular those for essential fatty acids including
      the long-chain polyunsaturated fatty acids (LC-PUFA) eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA). The ability to biosynthesize LC-PUFA is dependent
      upon the gene repertoire of fatty acyl desaturases (Fads) and elongases (Elovl),
      as well as their fatty acid specificities. In the present study we characterized
      both molecularly and functionally an orthologue of the desaturase fatty acid
      desaturase 2 (fads2) from A. gigas. The isolated sequence displayed the typical
      desaturase features, a cytochrome b5-domain with the heme-binding motif, two
      transmembrane domains and three histidine-rich regions. Functional
      characterization of A. gigas fads2 showed that, similar to other teleosts, the A.
      gigas fads2 exhibited a predominant Delta6 activity complemented with some
      capacity for Delta8 desaturation. Given that A. gigas belongs to one of the
      oldest teleostei lineages, the Osteoglossomorpha, these findings offer a
      significant insight into the evolution LC-PUFA biosynthesis in teleosts.

PMID- 27693629
TI  - Activation of the Tor/Myc signaling axis in intestinal stem and progenitor cells
      affects longevity, stress resistance and metabolism in drosophila.
AB  - The TOR (target of rapamycin) signaling pathway and the transcriptional factor
      Myc play important roles in growth control. Myc acts, in part, as a downstream
      target of TOR to regulate the activity and functioning of stem cells. Here we
      explore the role of TOR-Myc axis in stem and progenitor cells in the regulation
      of lifespan, stress resistance and metabolism in Drosophila. We found that both
      overexpression of rheb and myc-rheb in midgut stem and progenitor cells decreased
      the lifespan and starvation resistance of flies. TOR activation caused higher
      survival under malnutrition conditions. Furthermore, we demonstrate gut-specific
      activation of JAK/STAT and insulin signaling pathways to control gut integrity.
      Both genetic manipulations had an impact on carbohydrate metabolism and
      transcriptional levels of metabolic genes. Our findings indicate that activation
      of the TOR-Myc axis in midgut stem and progenitor cells influences a variety of
      traits in Drosophila.

PMID- 27693630
TI  - Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive
      inhibition of the Warburg effect by cetuximab.
AB  - Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing
      the Warburg effect and leading to inhibition of cancer cell metabolism. AMP
      activated protein kinase (AMPK) is activated after cetuximab treatment, and a
      sustained AMPK activity is a mechanism contributing to cetuximab resistance.
      Here, we investigated how acetyl-CoA carboxylase (ACC), a downstream target of
      AMPK, rewires cancer metabolism in response to cetuximab treatment. We found that
      introduction of experimental ACC mutants lacking the AMPK phosphorylation sites
      (ACC1_S79A and ACC2_S212A) into head and neck squamous cell carcinoma (HNSCC)
      cells protected HNSCC cells from cetuximab-induced growth inhibition. HNSCC cells
      with acquired cetuximab resistance contained not only high levels of T172
      phosphorylated AMPK and S79-phosphorylated ACC1 but also an increased level of
      total ACC. These findings were corroborated in tumor specimens of HNSCC patients
      treated with cetuximab. Cetuximab plus TOFA (an allosteric inhibitor of ACC)
      achieved remarkable growth inhibition of cetuximab-resistant HNSCC xenografts.
      Our data suggest a novel paradigm in which cetuximab-mediated activation of AMPK
      and subsequent phosphorylation and inhibition of ACC is followed by a
      compensatory increase in total ACC, which rewires cancer metabolism from
      glycolysis-dependent to lipogenesis-dependent.

PMID- 27693631
TI  - Disrupting MALAT1/miR-200c sponge decreases invasion and migration in
      endometrioid endometrial carcinoma.
AB  - Endometrioid endometrial carcinoma (EEC) is the most common gynecologic
      malignancy around the world. Epithelial-to-mesenchymal transition (EMT) is a core
      process during EEC cell invasion. The abnormal expression of the long noncoding
      RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) or miR-200
      family members were shown to facilitate EMT in multiple human cancers, but the
      regulatory mechanism by which MALAT1 and miR-200 act remains unknown. Previous
      studies have shown that miR-200 family members are enriched in EEC as well as
      melanoma and some ovarian carcinomas. In the present study, we first showed that
      miR-200c levels were higher in most EEC specimens than in non-tumor tissues,
      while MALAT1 levels were lower. Moreover, we found that miR-200c bound directly
      to MALAT1 using luciferase reporter and qRT-PCR assays. MALAT1 and miR-200c are
      reciprocally repressed, and TGF-beta increased MALAT1 expression by inhibiting
      miR-200c. When the interaction between miR-200c/MALAT1 was interrupted, the
      invasive capacity of EEC cells was decreased and EMT markers expression were
      altered in vitro. A xenograft tumor model was used to show that targeting the miR
      200c/MALAT1 axis inhibited EEC growth and EMT-associated protein expression in
      vivo. In summary, miR-200c/MALAT1 axis is a target with therapeutic potential in
      EEC. However, different expression model of miR-200c and MALAT1 in EEC with that
      in other organ carcinomas needs further mechanism researches.

PMID- 27693632
TI  - Comparative analysis of the relative potential of silver, Zinc-oxide and titanium
      dioxide nanoparticles against UVB-induced DNA damage for the prevention of skin
      carcinogenesis.
AB  - Sunscreen formulations containing UVB filters, such as Zinc-oxide (ZnO) and
      titanium-dioxide (TiO2) nanoparticles (NPs) have been developed to limit the
      exposure of human skin to UV-radiations. Unfortunately, these UVB protective
      agents have failed in controlling the skin cancer incidence. We recently
      demonstrated that silver nanoparticles (Ag-NPs) could serve as novel protective
      agents against UVB-radiations. Here our goal was to perform comparative analysis
      of direct and indirect UVB-protection efficacy of ZnO-, TiO2- and Ag-NPs. Sun
      protection-factor calculated based on their UVB-reflective/absorption abilities
      was the highest for TiO2-NPs followed by Ag- and ZnO-NPs. This was further
      confirmed by studying indirect protection of UVB radiation-induced death of HaCaT
      cells. However, only Ag-NPs were active in protecting HaCaT cells against direct
      UVB-induced DNA-damage by repairing bulky-DNA lesions through nucleotide-excision
      repair mechanism. Moreover, Ag-NPs were also effective in protecting HaCaT cells
      from UVB-induced oxidative DNA damage by enhancing SOD/CAT/GPx activity. In
      contrast, ZnO- and TiO2-NPs not only failed in providing any direct protection
      from DNA-damage, but rather enhanced oxidative DNA-damage by increasing ROS
      production. Together, these findings raise concerns about safety of ZnO- and TiO2
      NPs and establish superior protective efficacy of Ag-NPs.

PMID- 27693633
TI  - Hypoxia induces TWIST-activated epithelial-mesenchymal transition and
      proliferation of pancreatic cancer cells in vitro and in nude mice.
AB  - The epithelial-mesenchymal transition (EMT) plays a crucial role in pancreatic
      ductal adenocarcinoma (PDAC) development and progression. TWIST activated by
      intra-tumoral hypoxia functions to promote the EMT. We hypothesized that TWIST
      and the downstream gene pathway could mediate PDAC progression under hypoxia.
      Therefore, 90 PDAC tissue specimens were immunostained for TWIST and other
      proteins. Pancreatic cancer cell lines were used for in vitro experiments and
      nude mice were used to confirm the in vivo data. Expression of TWIST and HIF
      1alpha proteins was significantly upregulated, whereas expression of E-cadherin
      and p16 was down-regulated in PDAC tissues compared to that of non-tumor tissues
      and in tumor tissues obtained from patients with tumor involving splenic artery
      than those without splenic artery involvement. Up-regulated TWIST in tumor
      tissues were associated with worse prognosis in PDAC patients. The in vitro data
      showed that HIF-1alpha-induced TWIST overexpression promoted tumor cell growth
      and EMT under a hypoxic condition via TWIST interaction with Ring1B and EZH2. In
      vivo data showed that TWIST overexpression or a hypoxic condition induce
      xenograft growth, abdominal metastasis and low mouse survival, whereas knockdown
      of either Ring1B or EZH2 expression suppressed tumor xenograft growth and
      metastasis and prolonged survival of nude mice. TWIST was the key player in
      promotion of pancreatic cancer development and metastasis under a hypoxic
      condition through interaction with Ring1B and EZH2 to regulate expression of E
      cadherin and p16 proteins in pancreatic cancer cells.

PMID- 27693634
TI  - pVHL mediates K63-linked ubiquitination of IKKbeta, leading to IKKbeta
      inactivation.
AB  - Nuclear factor (NF)-kappaB is a transcription factor that plays an important role
      in many biological functions. Regulation of NF-kappaB activity is complicated,
      and ubiquitination is essential for NF-kappaB activation. Hypoxia can activate NF
      kappaB. However, the underlying mechanism remains unclear. pVHL is a tumour
      suppressor and functions as an adaptor of E3-ligase. In this study, we
      demonstrated that pVHL inhibits NF-kappaB by mediating K63-ubiquitination of
      IKKbeta, which is dependent on oxygen. We found that pVHL mediates K63-linked
      ubiquitination of IKKbeta, which is an upstream regulator of NF-kappaB. The pVHL
      mediated K63-ubiquitination of IKKbeta prevents TAK1 binding, which leads to the
      inhibition of IKKbeta phosphorylation and NF-kappaB activation. pVHL-mediated K63
      ubiquitination of IKKbeta is inhibited under hypoxia. DMOG, which is a specific
      inhibitor of prolyl hydroxylases, also suppresses K63-ubiquitination of IKKbeta.
      Prolyl hydroxylase (PHD) 1 enhances K63-ubiquitination of IKKbeta and inhibits
      IKKbeta phosphorylation. These results suggest a novel function for pVHL in
      mediating K63-linked ubiquitination of IKKbeta, which plays a role in the
      regulation of IKK/NF-kappaB signalling. The results also provide new insight into
      the mechanism of NF-kappaB activation through hypoxia.

PMID- 27693635
TI  - Immunological, anti-angiogenic and clinical effects of intratumoral interleukin
      12 electrogene therapy combined with metronomic cyclophosphamide in dogs with
      spontaneous cancer: A pilot study.
AB  - The immunological, anti-angiogenic and clinical effects of metronomic
      cyclophosphamide and 3 consecutive intratumoral interleukin (IL)-12 gene therapy
      (electrogene therapy (EGT)) treatments were evaluated in 6 dogs with spontaneous
      cancer. In all dogs, a decrease in peripheral leukocytes 2 days after IL-12 EGT
      coincided with erythema and swelling of the tumor. In the tumor, a transient
      increase in IL-12 levels was measured, whereas a continuous increase in
      interferon gamma (IFNgamma) and thrombospondin 1 (TSP-1) were determined in
      contrast to a continuous decrease in vascular endothelial growth factor (VEGF).
      In the serum, a transient increase in IL-12 and IL-10 levels were noted in
      contrast to a transient decrease in VEGF and TSP-1. The treatment resulted in a
      significant anti-angiogenic effect. Although all primary tumors continued to
      progress in time, this progression was slower than before treatment according to
      the contrast-enhanced ultrasound data. Besides the encouraging immunostimulatory
      and anti-angiogenic effects observed in all dogs we also noticed in 4 out of 6
      dogs clinically relevant improvements in quality of life and weight. These
      results hold great promise for combinatorial strategies of IL-12 EGT and
      metronomic chemotherapy with conventional antitumor (immuno)therapies.

PMID- 27693636
TI  - Hepatitis B virus mRNAs functionally sequester let-7a and enhance hepatocellular
      carcinoma.
AB  - Hepatitis B virus (HBV) infection induces hepatocarcinogenesis and malignant
      progression, yet global effects of the redundant viral mRNAs produced during
      infection are unexplored. Here, microRNA (miRNA) target prediction and whole
      genome expression analysis revealed that HBV pre-C/C mRNA leads to upregulation
      of multiple let-7a targeted genes. A let-7a complementary region from nt 86 to
      108 in the HBV genome was then identified in HBV pre-C/C, pre-S, and S mRNAs. The
      let-7a sequestration effect by HBV mRNAs was observed under transfection and
      virus infection, which is dependent on the let-7a response sequence. Moreover, we
      found reduced AGO2 binding, as well as functional mRNA and protein de-repression
      of let-7a targets (e.g., c-myc, K-RAS, and CCR7), upon viral mRNA expression. Let
      7a levels in the liver were significantly decreased in hepatocellular carcinoma
      (HCC) patients with HBV infection and were negatively correlated with
      intrahepatic pre-S2 mRNA levels. Finally, both in vitro and in vivo studies
      demonstrated that let-7a inhibition by HBV mRNAs resulted in enhanced HCC cell
      colony formation and tumor growth, providing evidence of the oncogenic potential
      of HBV mRNAs.

PMID- 27693637
TI  - The A2b adenosine receptor antagonist PSB-603 promotes oxidative phosphorylation
      and ROS production in colorectal cancer cells via adenosine receptor-independent
      mechanism.
AB  - PURPOSE: Adenosine is a multifaceted regulator of tumor progression. It modulates
      immune cell activity as well as acting directly on tumor cells. The A2b adenosine
      receptor (A2b-AR) is thought to be an important mediator of these effects. In
      this study we sought to analyze the contribution of the A2b-AR to the behavior of
      colorectal cancer cells. PRINCIPAL RESULTS: The A2b-AR antagonist PSB-603 changed
      cellular redox state without affecting cellular viability. Quantification of
      cellular bioenergetics demonstrated that PSB-603 increased basal oxygen
      consumption rates, indicative of enhanced mitochondrial oxidative
      phosphorylation. Unexpectedly, pharmacological and genetic approaches to
      antagonize AR-related signalling of PSB-603 did not abolish the response,
      suggesting that it was AR-independent. PSB-603 also induced acute increases in
      reactive oxygen species, and PSB-603 synergized with chemotherapy treatment to
      increase colorectal cancer cell death, consistent with the known link between
      cellular metabolism and chemotherapy response. MAJOR CONCLUSIONS: PSB-603 alters
      cellular metabolism in colorectal cancer cells and increases their sensitivity to
      chemotherapy. Although requiring more mechanistic insight into its A2b-AR
      independent activity, our results show that PSB-603 may have clinical value as an
      anti-colorectal cancer therapeutic.

PMID- 27693638
TI  - DNA-PKcs, a novel functional target of acriflavine, mediates acriflavine's p53
      dependent synergistic anti-tumor efficiency with melphalan.
AB  - Acriflavine (ACF), a known antibacterial drug, has recently been recognized as a
      suitable candidate for cancer chemotherapy. However, the molecular target of ACF
      is not fully understood, which limits its application in cancer therapy. In this
      study, we established a structure-specific probe-based pull-down approach to
      comprehensively profile the potential target of ACF, and we identified DNA
      dependent protein kinase catalytic subunit (DNA-PKcs) as the direct target of
      ACF. Since DNA-PKcs facilitates the repair process following DNA double-strand
      breaks, we further developed a drug combination strategy that combined ACF with
      the bifunctional alkylating agent melphalan, which exerted a p53-dependent
      synergistic efficacy against human cancer cells both in vitro and in vivo. With
      these findings, our study demonstrated that structure-specific probe-based pull
      down approaches can be used to identify new functional target of drug, and
      provided novel opportunities for the development of ACF-based antitumor
      chemotherapies.

PMID- 27693639
TI  - Integrative genomic and functional analysis of human oral squamous cell carcinoma
      cell lines reveals synergistic effects of FAT1 and CASP8 inactivation.
AB  - Oral squamous cell carcinoma (OSCC) is genetically highly heterogeneous, which
      contributes to the challenges of treatment. To create an in vitro model that
      accurately reflects this heterogeneity, we generated a panel of HPV-negative OSCC
      cell lines. By whole exome sequencing of the lines and matched patient blood
      samples, we demonstrate that the mutational spectrum of the lines is
      representative of primary OSCC in The Cancer Genome Atlas. We show that loss of
      function mutations in FAT1 (an atypical cadherin) and CASP8 (Caspase 8)
      frequently occur in the same tumour. OSCC cells with inactivating FAT1 mutations
      exhibited reduced intercellular adhesion. Knockdown of FAT1 and CASP8
      individually or in combination in OSCC cells led to increased cell migration and
      clonal growth, resistance to Staurosporine-induced apoptosis and, in some cases,
      increased terminal differentiation. The OSCC lines thus represent a valuable
      resource for elucidating the impact of different mutations on tumour behaviour.

PMID- 27693640
TI  - MELK is an oncogenic kinase essential for early hepatocellular carcinoma
      recurrence.
AB  - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related
      deaths worldwide. Many kinases have been found to be intimately involved in
      oncogenesis and the deregulation of kinase function has emerged as a major
      mechanism by which cancer cells evade normal physiological constraints on growth
      and survival. Previously, we have performed gene expression profile analysis on
      HCC samples and have identified a host of kinases that are remarkably
      overexpressed in HCC. Among these, the Maternal Embryonic Leucine Zipper Kinase
      (MELK) is highly overexpressed in HCC and its overexpression strongly correlates
      with early recurrence and poor patients' survival. Silencing MELK inhibited cell
      growth, invasion, stemness and tumorigenicity of HCC cells by inducing apoptosis
      and mitosis. We further showed that the overexpression of MELK in HCC samples
      strongly correlated with the cell cycle- and mitosis-related genes which are
      directly regulated as part of the forkhead transcription factor FoxM1-related
      cell division program. Together, our data establish MELK as an oncogenic kinase
      involved in the pathogenesis and recurrence of HCC and could provide a promising
      molecular target to develop therapeutic strategies for patients with advanced
      HCC.

PMID- 27693641
TI  - Microbicidal activity measured by flow cytometry: Optimization and
      standardization for detection of primary and functional deficiencies.
AB  - : Microbicidal activity is related to the production of reactive oxygen species
      (ROS) that can be measured by flow-cytometry using rhodamine 123 (R123). Few
      assays have been proposed to measure ROS production, usually on heparinized
      samples but none of them is standardized. Here we propose to improve the test by
      selecting polymorphonuclears (PMN) and monocytes, labelled and activated in one
      step to keep the test short, and to standardize the process even between
      different systems (i.e. NaviosTM and FACSCantoTM) using fluorescence intensity
      target setting ("FITS"). We applied this test on 15 patients without
      inflammation, 19 patients from an intensive care unit (ICU) and 11 healthy
      volunteers. RESULTS: Provided calcium restitution, we show that the test can be
      performed on EDTA that is a better sample preservative. The results were highly
      correlated between instruments (r2=0.898). PMN CD16 (and not CD14) expression was
      altered under stimulation with E. coli (MdFI=239.3+/-93.5) or PMA (139.7+/-76.8)
      as compared to resting sample (307.6+/-145.1). RH123 was strongly and
      homogeneously induced by PMA (14.2+/-6.6) and more heterogeneously by E. coli
      (MdFI 21.9+/-23.4) as compared to unstimulated PNN (0.9+/-1.3, p<0.0001). The
      test is useful not only for genetic disorders but also for secondary deficiencies
      as observed in ICU (E. coli RH123 MFI=10.5+/-11.1 patients vs 30.1+/-26.5 in
      healthy donors). In ICU, CD16 expression was already altered on unstimulated
      samples (MdFI=197.4+/-131.2 vs 418, 2+/-81.3 in healthy donors; p<=0.0001).
      Bacterial stimulation was dependent of the complement that partly explains
      deficiency to bacterial stimulus in ICU patients.

PMID- 27693642
TI  - CoVaccine HTTM adjuvant is superior to Freund's adjuvants in eliciting antibodies
      against the endogenous alarmin HMGB1.
AB  - Adjuvants are used to enhance the immune response against specific antigens for
      the production of antibodies, with the choice of adjuvant most critical for
      poorly immunogenic and self-antigens. This study quantitatively and qualitatively
      evaluated CoVaccine HTTM and Freund's adjuvants for eliciting therapeutic ovine
      polyclonal antibodies targeting the endogenous alarmin, high mobility group box-1
      (HMGB1). Sheep were immunised with HMGB1 protein in CoVaccine HTTM or Freund's
      adjuvants, with injection site reactions and antibody titres periodically
      assessed. The binding affinity of antibodies for HMGB1 and their neutralisation
      activity was determined in-vitro, with in vivo activity confirmed using a murine
      model of endotoxemia. Results indicated that CoVaccine HTTM elicited
      significantly higher antibody tires with stronger affinity and more functional
      potency than antibodies induced with Freund's adjuvants. These studies provide
      evidence that CoVaccine HTTM is superior to Freund's adjuvants for the production
      of antibodies to antigens with low immunogenicity and supports the use of this
      alternative adjuvant for clinical and experimental use antibodies.

PMID- 27693643
TI  - Timing of upper endoscopy influences outcomes in patients with acute nonvariceal
      upper GI bleeding.
AB  - BACKGROUND AND AIMS: Current guidelines advise that upper endoscopy be performed
      within 24 hours of presentation in patients with acute nonvariceal upper GI
      bleeding (UGIB). However, the role of urgent endoscopy (<12 hours) is
      controversial. Our aim was to assess whether patients admitted with acute
      nonvariceal UGIB with lower-risk versus high-risk bleeding have different
      outcomes with urgent compared with nonurgent endoscopy. METHODS: A retrospective
      cohort study was conducted of patients admitted to an academic hospital with
      nonvariceal UGIB. The primary outcome was a composite of inpatient death from any
      cause, inpatient rebleeding, need for surgical or interventional radiologic
      intervention, or endoscopic reintervention. The Glasgow-Blatchford score (GBS)
      was calculated; lower risk was defined as a GBS < 12, and high risk was defined
      as a GBS >= 12. RESULTS: Of 361 patients, 37 patients (10%) experienced the
      primary outcome. Patients who underwent urgent endoscopy had a greater than 5
      fold increased risk of reaching the composite outcome (unadjusted odds ratio
      [OR], 5.6; 95% confidence interval [CI], 2.8-11.4; P < .001). Lower-risk patients
      who were taken urgently to endoscopy were more likely to reach the composite
      outcome (adjusted OR, 0.71 per 6 hours; 95% CI, 0.55-0.91; P = .008). However, in
      the high-risk patients, time to endoscopy was not a significant predictor of the
      primary outcome (adjusted OR, 0.93 per 6 hours; 95% CI, 0.77-1.13; P = .47;
      adjusted P for interaction = .039). CONCLUSION: Urgent endoscopy is a predictor
      of worse outcomes in select patients with acute nonvariceal UGIB.

PMID- 27693644
TI  - EUS-guided portal pressure gradient measurement with a simple novel device: a
      human pilot study.
AB  - BACKGROUND AND AIMS: Portal hypertension (PH) is a serious adverse event of liver
      cirrhosis. The hepatic venous pressure gradient or portal pressure gradient (PPG)
      accurately reflects the degree of PH and is the single best prognostic indicator
      in liver disease. This is usually obtained by interventional radiology (IR),
      although it is not routinely performed. Recently, we developed a simple novel
      technique for EUS-guided PPG measurement (PPGM). Our animal studies showed
      excellent correlation between EUS-PPGM and IR-PPGM. We present the first human
      pilot study of EUS-PPGM in patients with liver disease. METHODS: EUS-PPGM was
      performed by experienced endosonographers using a linear echoendoscope, a 25
      gauge fine-needle aspiration needle, and a novel compact manometer. The portal
      vein and hepatic vein (or inferior vena cava) were targeted using a transgastric
      transduodenal approach. Clinical parameters of PH were evaluated in each patient.
      Feasibility was defined as successful PPGM in each patient. Safety was based on
      adverse events captured in a postprocedural interview. RESULTS: Twenty-eight
      patients underwent EUS-PPGM with 100% technical success and no adverse events.
      PPG ranged from 1.5 to 19 mm Hg and had excellent correlation with clinical
      parameters of portal hypertension including the presence of varices (P = .0002),
      PH gastropathy (P = .007), and thrombocytopenia (P = .036). PPG was increased in
      patients with high clinical evidence of cirrhosis (P = .005). CONCLUSION: This
      novel technique of EUS-PPGM using a 25-gauge needle and compact manometer is
      feasible and appears safe. Given the availability of EUS and the simplicity of
      the manometry setup, EUS-guided PPG may represent a promising breakthrough for
      procuring indispensable information in the management of patients with liver
      disease.

PMID- 27693646
TI  - Dipotassium ethylenediaminetetraacetic acid is better than tripotassium salt for
      electrochemiluminescence insulin measurement.
AB  - Previous studies reported that stability of insulin was better on
      ethylenediaminetetraacetic acid (EDTA) plasma sample than serum sample. However,
      those studies used tripotassium EDTA (K3-EDTA) tubes, rather than dipotassium
      EDTA (K2-EDTA) tubes which are more commonly used in laboratories. We
      investigated the impact of preservative type of EDTA (K2 or K3) on the stability
      of C-peptide and insulin at 4 degrees C and at room temperature room. Our study
      has identified that K2-EDTA achieves longer stability of insulin but does not
      improve the stability of C-peptide. Insulin and C-peptide are stable 24h on the
      same K2-EDTA sample at room temperature.

PMID- 27693645
TI  - Comparing 3 guidelines on the management of surgically removed pancreatic cysts
      with regard to pathological outcome.
AB  - BACKGROUND AND AIMS: Currently, 3 guidelines are available for the management of
      pancreatic cysts. These guidelines vary in their indication for resection of high
      risk cysts. We retrospectively compared the final pathologic outcome of
      surgically removed pancreatic cysts with the indications for resection according
      to 3 different guidelines. METHODS: Patients who underwent pancreatic resection
      were extracted from our prospective pancreatic cyst database (2006-present). The
      final histopathologic diagnosis was compared with the initial indication for
      surgery stated by the guidelines of the International Association of
      Pancreatology (IAP), European Study Group on Cystic tumors of the Pancreas and
      American Gastroenterological Association (AGA). We considered surgery in
      retrospect justified for malignancy, high-grade dysplasia, solid pseudopapillary
      neoplasms, neuroendocrine tumors or symptom improvement. Furthermore, we
      evaluated the patients with suspected intraductal papillary mucinous neoplasm
      (IPMN) separately. RESULTS: Overall, 115 patients underwent pancreatic resection.
      The preoperative diagnosis was correct in 83 of 115 patients (72%) and
      differentiation between benign and premalignant in 99 of 115 patients (86%). In
      retrospect, surgery was justified according to the aforementioned criteria in 52
      of 115 patients (45%). For patients with suspected IPMN (n = 75) resection was
      justified in 36 of 67 (54%), 36 of 68 (53%), and 32 of 54 (59%) of patients who
      would have had surgery based on the IAP, European, or AGA guidelines,
      respectively. The AGA guideline would have avoided resection in 21 of 75 (28%)
      patients, versus 8 of 75 (11%) and 7 of 75 (9%) when the IAP or European
      guideline would have been applied strictly. Nevertheless, 4 of 33 patients (12%)
      with high-grade dysplasia or malignancy would have been missed with the AGA
      guidelines, compared with none with the IAP or European guidelines. CONCLUSION:
      Although fewer patients undergo unnecessary surgery based on the AGA guidelines,
      the risk of missing malignancy or high-grade dysplasia with this guideline seems
      considerably high.

PMID- 27693647
TI  - Factors Associated with Increased Pain in Primary Dysmenorrhea: Analysis Using a
      Multivariate Ordered Logistic Regression Model.
AB  - STUDY OBJECTIVE: In the literature about primary dysmenorrhea (PD), either a pain
      gradient has been studied just in women with PD or pain was assessed as a binary
      variable (presence or absence). Accordingly, we decided to carry out a study in
      young women to determine possible factors associated with intense pain. DESIGN: A
      cross-sectional observational study. SETTING: A Spanish University in 2016.
      PARTICIPANTS: A total of 306 women, aged 18-30 years. INTERVENTIONS: A
      questionnaire was filled in by the participants to assess associated factors with
      dysmenorrhoea. MAIN OUTCOME MEASURES: Our outcome measure was the Andersch and
      Milsom scale (grade from 0 to 3). DEFINITION: grade 0 (menstruation is not
      painful and daily activity is unaffected), grade 1 (menstruation is painful but
      seldom inhibits normal activity, analgesics are seldom required, and mild pain),
      grade 2 (daily activity affected, analgesics required and give relief so that
      absence from work or school is unusual, and moderate pain), and grade 3 (activity
      clearly inhibited, poor effect of analgesics, vegetative symptoms and severe
      pain). RESULTS: Factors significantly associated with more extreme pain: a higher
      menstrual flow (odds ratio [OR], 2.11; P < .001), a worse quality of life (OR,
      0.97; P < .001) and use of medication for PD (OR, 8.22; P < .001). CONCLUSION: We
      determined factors associated with extreme pain in PD in a novel way. Further
      studies are required to corroborate our results.

PMID- 27693648
TI  - Balloon Dilation and Electrohydraulic Lithotripsy for Treating an Impacted
      Duodenal Bezoar.

PMID- 27693649
TI  - MiR-17 targets PTEN and facilitates glial scar formation after spinal cord
      injuries via the PI3K/Akt/mTOR pathway.
AB  - OBJECTIVES: We attempted to discover the regulatory role of miR-17 and PTEN in
      glial scar formation accompanied with spinal cord injuries. METHODS: We
      established a spinal cord injury (SCI) model in mice which were transfected with
      different groups of adenoviruses: miR-17 mimics, miR-17 inhibitors and PTEN
      cDNAs. The improvement of hind limb functions was assessed using the 21-point
      Basso-Beattie-Bresnahan (BBB) locomotion scale. Immunohistochemistry was used to
      detect the expression levels of glial fibrillary acidic protein (GFAP), Vimentin
      and neurofilaments. The expression of miR-17 was quantified using Real time-PCR
      (RT-PCR). Western blot was conducted to detect the expressions of PTEN, PI3K,
      Akt, mTOR and S6. Finally, dual luciferase reporter gene assay was conducted to
      confirm the target relationship between miR-17 and PTEN. RESULTS: The model group
      exhibited significantly increased expression levels of GFAP, Vimentin, miR-17,
      PTEN, PI3K, Akt and mTOR. The above trend was enhanced by the transfection of miR
      17 mimics (P<0.05). By contrast, the transfection of miR-17 inhibitors
      significantly down-regulated the expression of GFAP, Vimentin, PTEN, PI3K, Akt,
      mTOR and p-S6 whereas the expression of GFAP, Vimentin, PI3K, Akt, mTOR and p-S6
      in the cells transfected with PTEN cDNAs significantly decreased (P<0.05). Also,
      the transfection of miR-17 inhibitors and PTEN cDNAs alleviated the astrogliosis
      in SCI lesions, contributed to the regeneration of nerve filament and improved
      the functional recovery of the hind limb of mice. Finally, the targeting
      relationship between miR-17 and PTEN was verified by the dual luciferase reporter
      gene assay. CONCLUSION: MiR-17 is able to target PTEN and stimulate the
      PI3K/Akt/mTOR pathway. The formation of glial scar resulted from spinal cord
      injuries can be reduced either by inhibiting miR-17 or by overexpressing PTEN.

PMID- 27693651
TI  - DNA-Damage Response RNA-Binding Proteins (DDRBPs): Perspectives from a New Class
      of Proteins and Their RNA Targets.
AB  - Upon DNA damage, cells trigger an early DNA-damage response (DDR) involving DNA
      repair and cell cycle checkpoints, and late responses involving gene expression
      regulation that determine cell fate. Screens for genes involved in the DDR have
      found many RNA-binding proteins (RBPs), while screens for novel RBPs have
      identified DDR proteins. An increasing number of RBPs are involved in early
      and/or late DDR. We propose to call this new class of actors of the DDR, which
      contain an RNA-binding activity, DNA-damage response RNA-binding proteins
      (DDRBPs). We then discuss how DDRBPs contribute not only to gene expression
      regulation in the late DDR but also to early DDR signaling, DNA repair, and
      chromatin modifications at DNA-damage sites through interactions with both long
      and short noncoding RNAs.

PMID- 27693652
TI  - Responses to abiotic environmental stresses among phylloplane and soil isolates
      of Beauveria bassiana from two holm oak ecosystems.
AB  - The response of entomopathogenic mitosporic ascomycete (EMAs) to abiotic stresses
      might be adapted to the microhabitats in which they inhabit. In phylloplane,
      these organisms are more exposed to such stresses than they are in soil, which
      may have led to adaptation to this environment. In the present work, we
      investigate whether Beauveria bassiana genotype or isolation habitat, i.e., soil
      or phylloplane, within the same geographic area influences their responses to key
      environmental stresses, such as temperature, moisture and ultraviolet radiation
      (UV-B), which can affect their successful use in microbial control. Twenty
      isolates of B. bassiana obtained from the soil and phylloplane in two ecosystems
      from southern Spain (holm oak dehesa and a reforested area) were selected to
      study the population distribution of these isolates and evaluate their thermal,
      humidity and UV-B requirements. Molecular characterization was conducted by using
      elongation factor-1alpha (EF-1alpha), the intergenic nuclear region Bloc and 15
      microsatellite primers. The cluster analysis based on concatenated EF-1alpha and
      Bloc sequences grouped the 20 isolates into five clades within B. basiana, with
      Clades a, b, d and e containing both soil and phylloplane isolates and Clade c
      including three phylloplane isolates. The dendrogram and the minimal spanning
      network generated from the genetic distances among multilocus genotypes showed
      four divergent groups corresponding to the five clades obtained based on the
      sequence data (Clades b and d were represented in the same group), with a high
      degree of shared alleles within groups and few alleles shared among groups.
      Although no relationship was found between MLG and the habitat (soil or
      phylloplane) of isolation, isolates grouped into Clade c, all of which were
      collected from phylloplane, formed a separate group of MLGs. To investigate our
      hypothesis, the responses to temperature (germination and colony growth evaluated
      in the range 15-35 degrees C), water activity (conidia germination evaluated
      against values of aw between 1 and 0.862) and UV-B exposure (conidia exposed to
      920 or 1200mWm-2 for 2, 4 or 6h) of the soil and phylloplane isolates from the
      five clades were investigated. No associations of isolate-specific genetic or
      physiological characteristics with isolate habitat, i.e., soil or phylloplane,
      were found. These results provide no support for the hypothesis that EMAs strains
      from the phylloplane have evolved to resist unfavourable environmental
      conditions.

PMID- 27693650
TI  - MOMP from Campylobacter jejuni Is a Trimer of 18-Stranded beta-Barrel Monomers
      with a Ca2+ Ion Bound at the Constriction Zone.
AB  - The Gram-negative organism Campylobacter jejuni is the major cause of food
      poisoning. Unlike Escherichia coli, which has two major porins, OmpC and OmpF, C.
      jejuni has one, termed major outer membrane protein (MOMP) through which
      nutrients and antibiotics transit. We report the 2.1-A crystal structure of C.
      jejuni MOMP expressed in E. coli and a lower resolution but otherwise identical
      structure purified directly from C. jejuni. The 2.1-A resolution structure of
      recombinant MOMP showed that although the protein has timeric arrangement similar
      to OmpC, it is an 18-stranded, not 16-stranded, beta-barrel. The structure has
      identified a Ca2+ bound at the constriction zone, which is functionally
      significant as suggested by molecular dynamics and single-channel experiments.
      The water-filled channel of MOMP has a narrow constriction zone, and single
      molecule studies show a monomeric conductivity of 0.7+/-0.2 nS and a trimeric
      conductance of 2.2+/-0.2 nS. The ion neutralizes negative charges at the
      constriction zone, reducing the transverse electric field and reversing ion
      selectivity. Modeling of the transit of ciprofloxacin, an antibiotic of choice
      for treating Campylobacter infection, through the pore of MOMP reveals a
      trajectory that is dependent upon the presence metal ion.

PMID- 27693653
TI  - Relationships between indoor radon concentrations, thermal retrofit and dwelling
      characteristics.
AB  - A monitoring campaign was conducted on a sample of more than 3400 dwellings in
      Brittany, France from 2011 to 2014. The measurements were collected using one
      passive dosimeter per dwelling over two months during the heating season,
      according to the NF ISO 11665-8 (2013) standard. Moreover, building
      characteristics such as the period of construction, construction material, type
      of foundation, and thermal retrofit were determined using a questionnaire. The
      final data set consisted of 3233 houses with the measurement results and the
      questionnaire answers. Multivariate linear regression models were applied to
      explore the relationships between the indoor radon concentrations and building
      characteristics, particularly the thermal retrofit. The geometric mean of the
      indoor radon concentration was 155 Bq m-3 (with a geometric standard deviation of
      3). The houses that had undergone a thermal retrofit had a higher average radon
      concentration than those that had not, which may have been due to a decrease in
      air permeability of the building envelope following rehabilitation work that did
      not systematically include proper management of the ventilation. Other building
      characteristics, primarily the building material and the foundation type, were
      associated with the indoor radon concentration. The indoor radon concentrations
      were higher in older houses built with granite or other stone, with a slab-on
      grade foundation and without any ventilation system.

PMID- 27693654
TI  - Assessment of the reduction in levels of exposure to harmful and potentially
      harmful constituents in Japanese subjects using a novel tobacco heating system
      compared with conventional cigarettes and smoking abstinence: A randomized
      controlled study in confinement.
AB  - Smoking conventional cigarettes (CCs) exposes smokers to harmful and potentially
      harmful constituents (HPHCs). The Tobacco Heating System 2.2 (THS 2.2), a
      candidate modified risk tobacco product, was developed to reduce or eliminate the
      formation of HPHCs, while preserving as much as possible the taste, sensory
      experience, nicotine delivery profile and ritual characteristics of CC. This
      randomized, controlled, open-label study in confinement for 5 day exposure aimed
      to demonstrate the reduction in exposure to selected HPHCs, to assess nicotine
      uptake and subjective effects, in participants switching to THS 2.2 (n = 80)
      compared to participants continuing smoking CCs (n = 40) and abstaining from
      smoking (n = 40). The subjects were randomized according to sex and daily CC
      consumption. The levels of biomarkers of exposure to HPHCs were significantly
      reduced in participants switching to THS 2.2, compared to CC use. More
      importantly, the magnitude of exposure reduction observed was close to that which
      was seen in participants who abstained from smoking for 5 days, while nicotine
      uptake was maintained. Reduction in urge-to-smoke was comparable between THS and
      CC groups, however THS 2.2 was slightly less satisfactory than CCs. The new,
      alternative tobacco product THS 2.2 was well tolerated.

PMID- 27693655
TI  - Long term detection of seasonal influenza RNA in faeces and intestine - Author's
      Reply.

PMID- 27693656
TI  - Association of active human herpesvirus-6 (HHV-6) infection with autoimmune
      thyroid gland diseases.
AB  - OBJECTIVES: Viral infections frequently have been cited as important
      environmental factors implicated in the onset of autoimmune thyroiditis (AIT).
      The aim of this study was to determine the involvement of HHV-6 infection in the
      development of autoimmune thyroiditis. METHODS: This study included 45 patients
      (42 female and 3 male; median age 47.00 IQR 38.50-57.00) with histologically,
      laboratory, and clinically confirmed autoimmune thyroiditis, as well as 30
      autopsied subjects (26 female and 4 male; median age 58.50, IQR 51.50-67.00)
      without thyroid pathologies and 30 healthy blood donors (25 female and 5 male;
      median age 33.50, IQR 27.75-44.25) as controls. Results were obtained by applying
      molecular virology and immunohistochemistry techniques. RESULTS: The presence of
      persistent HHV-6 infection in AIT patients was significantly higher (p 0.0058)
      than in the control group (44/45 (98%) vs. 23/30 (77%), respectively). Also, a
      significantly higher frequency of HHV-6 activation marker (U79/80 mRNA) was found
      in patients' thyroid gland tissue samples with AIT in comparison with the control
      group (18/44 (41%) vs. 1/17 (6%), respectively; p 0.0118). The median HHV-6 load
      was found to be higher in patients with active viral infection than in patients
      without it (2147, IQR 971-4188 vs. 551, IQR 145-1589 copies/1*106 cells; p
      0.003). The presence of HHV-6 antigen expression was demonstrated in
      intrafollicular cellular clusters and immunohistochemistry indicated thyrocytes
      in the follicle wall. CONCLUSIONS: These findings provide evidence of strong HHV
      6 infection association with AIT development.

PMID- 27693657
TI  - De-constructing de-escalation.

PMID- 27693658
TI  - Staphylococcus aureus colonization at ICU admission as a risk factor for
      developing S. aureus ICU pneumonia.
AB  - OBJECTIVE: To quantify the incidence of intensive care unit (ICU)-acquired
      pneumonia caused by Staphylococcus aureus (S. aureus) and its association with S.
      aureus colonization at ICU admission. METHODS: This was a post-hoc analysis of
      two cohort studies in critically ill patients. The primary outcome was the
      incidence of microbiologically confirmed S. aureus ICU-acquired pneumonia.
      Incidences of S. aureus ICU pneumonia and associations with S. aureus
      colonization at ICU admission were determined using competing risks analyses. In
      all ICUs, patients were screened for respiratory tract S. aureus carriage on
      admission as part of infection control policies. Pooling of data was not deemed
      possible because of heterogeneity in baseline differences in patient population.
      RESULTS: The two cohort studies contained data of 9156 ICU patients. The average
      carriage rate of S. aureus among screened patients was 12.7%. In total, 1185
      (12.9%) patients developed ICU pneumonia. Incidences of S. aureus ICU pneumonia
      were 1.33% and 1.08% in cohorts 1 and 2, respectively. After accounting for
      competing events, the adjusted subdistribution hazard ratio (SHR) of S. aureus
      colonization at admission for developing S. aureus ICU pneumonia was 9.55 (95% CI
      5.31-17.18) in cohort 1 and 14.54 (95% CI 7.24-29.21) in cohort 2. CONCLUSION:
      The overall cumulative incidence of S. aureus ICU pneumonia in these ICUs was
      low. Patients colonized with S. aureus at ICU admission had an up to 15 times
      increased risk for developing this outcome compared with non-colonized patients.

PMID- 27693659
TI  - HCV and diabetes: towards a 'sustained' glycaemic improvement after treatment
      with DAAs?

PMID- 27693660
TI  - Increased adult neurogenesis in mice with a permanent overexpression of the
      postsynaptic 5-HT1A receptor.
AB  - Depression is among the leading causes of disability and disease burden. Recent
      studies point to an involvement of altered serotonin1A receptor (5-HT1AR) 
      mediated adult neurogenesis in depression. However, the exact underlying
      mechanisms remain unclear, mainly due to the complexity of the serotonergic
      system with its various receptors and their locations. Mice with permanent
      overexpression of postsynaptic 5-HT1ARs (OE mice) represent a unique tool for
      investigating the involvement of postsynaptic 5-HT1ARs in this context. Correct 5
      HT1AR coupling and functioning has been demonstrated earlier, indicating that
      more postsynaptic 5-HT1ARs can be activated in these mice. Initially we examined
      morphometric parameters of the dentate gyrus (DG) and the prefrontal cortex as
      they are involved in adult hippocampal neurogenesis and/or depression. The volume
      of the DG in OE mice was increased in comparison to wildtype controls. We
      therefore investigated parameters of adult neurogenesis by the bromodeoxyuridine
      method. Proliferation and survival of newborn cells in the DG of OE mice were
      significantly increased. Significant increases in survived neurons were only
      detected in the female but not in the male subgroup. Additional staining for
      early precursor cells (Sox2) and progenitor cells of the neuronal lineage
      (doublecortin) showed an increase in type-1/2a as well as in type-2b/3 cells in
      OE mice. Our study suggests a leading role of the postsynaptic 5-HT1AR in adult
      hippocampal neurogenesis and might open an important link to depression.

PMID- 27693661
TI  - Effect of muscle relaxation in the foot on simultaneous muscle contraction in the
      contralateral hand.
AB  - We investigated the effects of foot muscle relaxation and contraction on muscle
      activities in the hand on both ipsilateral and contralateral sides. The subjects
      sat in an armchair with hands in the pronated position. They were able to freely
      move their right/left hand and foot. They performed three tasks for both
      ipsilateral (right hand and right foot) and contralateral limb coordination (left
      hand and right foot for a total of six tasks). These tasks involved: (1) wrist
      extension from a flexed (resting) position, (2) wrist extension with simultaneous
      ankle dorsiflexion from a plantarflexed (resting) position, and (3) wrist
      extension with simultaneous ankle relaxation from a dorsiflexed position. The
      subjects performed each task as fast as possible after hearing the start signal.
      Reaction time for the wrist extensor contraction (i.e. the degree to which it
      preceded the motor reaction time), as observed in electromyography (EMG), became
      longer when it was concurrently done with relaxation of the ankle dorsiflexor.
      Also, the magnitude of EMG activity became smaller, as compared with activity
      when wrist extensor contraction was done alone or with contraction of the ankle
      dorsiflexor. These effects were observed not only for the ipsilateral hand, but
      also for the contralateral hand. Our findings suggest that muscle relaxation in
      one limb interferes with muscle contraction in both the ipsilateral and
      contralateral limbs.

PMID- 27693662
TI  - Gastrin-releasing peptide receptor mediates the excitation of preoptic GABAergic
      neurons by bombesin.
AB  - Bombesin, a pan agonist of the bombesin-like peptide receptor family, elicits
      potent hypothermia when applied centrally. The signaling mechanisms involved are
      not known. Here we report that GABAergic preoptic neurons express gastrin
      releasing peptide (GRP) receptors and are directly excited by GRP or bombesin.
      This effect was abolished by a GRP receptor antagonist. A partially overlapping
      group of preoptic GABAergic neurons express bombesin-like receptor 3 (BRS3),
      however their activation results in a decrease in firing rate. The excitatory
      effects of bombesin or GRP were not affected by BRS3 antagonist. GRP activated a
      Ca2+-dependent inward nonselective cationic current and Ca2+ release from
      intracellular stores. Our data indicate that GRP receptors mediate the excitatory
      effects of bombesin in preoptic neurons.

PMID- 27693663
TI  - Active immunization with the peptide epitope vaccine Abeta3-10-KLH induces a Th2
      polarized anti-Abeta antibody response and decreases amyloid plaques in APP/PS1
      transgenic mice.
AB  - Active amyloid-beta (Abeta) immunotherapy is effective in preventing Abeta
      deposition, facilitating plaque clearance, and improving cognitive functions in
      mouse models of Alzheimer's disease (AD). Developing a safe and effective AD
      vaccine requires a delicate balance between inducing adequate humoral immune
      responses and avoiding T cell-mediated autoimmune responses. In this study, we
      designed 2 peptide epitope vaccines, Abeta3-10-KLH and 5Abeta3-10, prepared
      respectively by coupling Abeta3-10 to the immunogenic carrier protein keyhole
      limpet hemocyanin (KLH) or by joining 5 Abeta3-10 epitopes linearly in tandem.
      Young APP/PS1 mice were immunized subcutaneously with Abeta3-10-KLH or 5Abeta3-10
      mixed with Freund's adjuvant, and the immunopotencies of these Abeta3-10 peptide
      vaccines were tested. Abeta3-10-KLH elicited a robust Th2-polarized anti-Abeta
      antibody response and inhibited Abeta deposition in APP/PS1 mice. However,
      5Abeta3-10 did not induce an effective humoral immune response. These results
      indicated that Abeta3-10-KLH may be a safe and efficient vaccine for AD and that
      conjugating the antigen to a carrier protein may be more effective than linking
      multiple peptide antigens in tandem in applications for antibody production and
      vaccine preparation.

PMID- 27693665
TI  - Towards a cognitive-learning formulation of youth anxiety: A narrative review of
      theory and evidence and implications for treatment.
AB  - The tendency to disproportionately allocate attention to threat stimuli, to
      evaluate ambiguous or benign situations as overly threatening, and to exhibit
      overgeneralised and indiscriminate conditioned fear responses to threat and safe
      stimuli are hallmark clinical correlates of pathological anxiety. Investigation
      of these processes in children and adolescents suggests that anxiety-related
      differences increase with age, and that the specific conditions under which
      anxious children differ from non-anxious peers are poorly understood.
      Furthermore, research on cognitive biases and fear conditioning in anxious
      children and adolescents has progressed as quite distinct lines of investigation.
      Greater integration of key tenets from each perspective could advance knowledge
      and provide new directions for improving treatments. The purpose of this paper is
      threefold. First, we provide a qualitative review of the key principles from
      cognitive and conditioning theories of anxiety and the associated empirical
      research, including the underlying neurophysiological basis of these processes in
      anxious children and adolescents, in order to delineate the conditions under
      which anxiety-specific differences in threat-related cognitive biases and
      overgeneralised conditioned fear manifest in children and adolescents. Second, we
      synthesize these theoretical and empirical insights to propose a cognitive
      learning formulation of anxiety in children and adolescents. We propose that
      conditioning and cognitive factors linked to differences in engagement of
      underlying neural circuits across development contribute to an internal
      representation of a wide range of stimuli as threatening, to which anxious
      children and adolescents adopt maladaptive attention regulation patterns of
      predominantly threat monitoring or threat avoidance. These maladaptive attention
      regulation patterns differentiate anxious children and adolescents in terms of
      predominantly high cognitive distress (e.g., worry and rumination) and high
      behavioural avoidance respectively. Third, we consider the clinical implications
      of the cognitive-learning formulation for understanding outcomes from current
      treatments and provide suggestions for improving treatment outcomes.

PMID- 27693666
TI  - Pericellular plasma clot negates the influence of scaffold stiffness on
      chondrogenic differentiation.
AB  - : Matrix stiffness is known to play a pivotal role in cellular differentiation.
      Studies have shown that soft scaffolds (<2-3kPa) promote cellular aggregation and
      chondrogenesis, whereas, stiffer ones (>10kPa) show poor chondrogenesis in vitro.
      In this work we investigated if fibrin matrix from clotted blood can act as a
      soft surrogate which nullifies the influence of the underlying stiff scaffold,
      thus promoting chondrogenesis irrespective of bulk scale scaffold stiffness. For
      this we performed in vitro chondrogenesis on soft (~1.5kPa) and stiff (~40kPa)
      gelatin scaffolds in the presence and absence of pericellular plasma clot. Our
      results demonstrated that in absence of pericellular plasma clot, chondrocytes
      showed efficient condensation and cartilaginous matrix secretion only on soft
      scaffolds, whereas, in presence of pericellular plasma clot, cell rounding and
      cartilaginous matrix secretion was observed in both soft and stiff scaffolds.
      More specifically, significantly higher collagen II, chondroitin sulfate and
      aggrecan deposition was observed in soft scaffolds, and soft and stiff scaffolds
      with pericellular plasma clot as compared to stiff scaffolds without pericellular
      plasma clot. Moreover, collagen type I, a fibrocartilage/bone marker was
      significantly higher only in stiff scaffolds without plasma clot. Therefore, it
      can be concluded that chondrocytes surrounded by a soft fibrin network were
      unable to sense the stiffness of the underlying scaffold/substrate and hence
      facilitate chondrogenesis even on stiff scaffolds. This understanding can have
      significant implications in the design of scaffolds for cartilage tissue
      engineering. STATEMENT OF SIGNIFICANCE: Cell fate is influenced by the mechanical
      properties of cell culture substrates. Outside the body, cartilage progenitor
      cells express significant amounts of cartilage-specific markers on soft scaffolds
      but not on stiff scaffolds. However, when implanted in joints, stiff scaffolds
      show equivalent expression of markers as seen in soft scaffolds. This disparity
      in existing literature prompted our study. Our results suggest that encapsulation
      of cells in a soft plasma clot, present in any surgical intervention, prevents
      their perception of stiffness of the underlying scaffold, and hence the ability
      to distinguish between soft and stiff scaffolds vanishes. This finding would aid
      the design of new scaffolds that elicit cartilage-like biochemical properties
      while simultaneously being mechanically comparable to cartilage tissue.

PMID- 27693664
TI  - Pooled patient-level meta-analysis of children and adults completing a computer
      based anxiety intervention targeting attentional bias.
AB  - Computer-based approaches, such as Attention Bias Modification (ABM), could help
      improve access to care for anxiety. Study-level meta-analyses of ABM have
      produced conflicting findings and leave critical questions unresolved regarding
      ABM's mechanisms of action and clinical potential. We pooled patient-level
      datasets from randomized controlled trials of children and adults with high
      anxiety. Attentional bias (AB) towards threat, the target mechanism of ABM, was
      tested as an outcome and a mechanistic mediator and moderator of anxiety
      reduction. Diagnostic remission and Liebowitz Social Anxiety Scale (LSAS) were
      clinical outcomes available in enough studies to enable pooling. Per-patient data
      were obtained on at least one outcome from 13/16 eligible studies [86% of
      eligible participants; n=778]. Significant main effects of ABM on diagnostic
      remission (ABM-22.6%, control-10.8%; OR=2.57; p=0.006) and AB (beta* (95%CI)=
      0.63 (-0.83, -0.42); p<0.00005) were observed. There was no main effect of ABM on
      LSAS. However, moderator analyses suggested ABM was effective for patients who
      were younger (<=37y), trained in the lab, and/or assessed by clinicians. Under
      the same conditions where ABM was effective, mechanistic links between AB and
      anxiety reduction were supported. Under these specific circumstances, ABM reduces
      anxiety and acts through its target mechanism, supporting ABM's theoretical basis
      while simultaneously suggesting clinical indications and refinements to improve
      its currently limited clinical potential.

PMID- 27693667
TI  - Neural mechanisms underlying cognitive inflexibility in Parkinson's disease.
AB  - Cognitive inflexibility is a hallmark of executive dysfunction in Parkinson's
      disease (PD). This deficit consistently manifests itself in a PD-related increase
      in the number of perseverative errors committed on the Wisconsin Card Sorting
      Test (WCST). However, the neural processes underlying perseverative WCST
      performance in PD are still largely unknown. The present study is the first to
      investigate the event-related potential (ERP) correlates of cognitive
      inflexibility on the WCST in PD patients. Thirty-two PD patients and 35 matched
      control participants completed a computerized version of the WCST while the
      electroencephalogram (EEG) was recorded. Behavioral results revealed the expected
      increase in perseverative errors in patients with PD. ERP analysis focused on two
      established indicators of executive processes: the fronto-central P3a as an index
      of attentional orienting and the sustained parietal positivity (SPP) as an index
      of set-shifting processes. In comparison to controls, P3a amplitudes were
      significantly attenuated in PD patients. Regression analysis further revealed
      that P3a and SPP amplitudes interactively contributed to the prediction of
      perseverative errors in PD patients: The number of perseverative errors was only
      increased when both ERP amplitudes were attenuated. Notably, the two ERP markers
      of executive processes accounted for more than 40% of the variance in
      perseverative errors in PD patients. We conclude that cognitive inflexibility in
      PD occurs when the neural bases of multiple executive processes are affected by
      the pathophysiology of PD. The combined measurement of P3a and SPP might yield an
      electrophysiological marker of cognitive inflexibility in PD.

PMID- 27693668
TI  - Altered functional connectivity during self- and close other-reflection in
      patients with bipolar disorder with past psychosis and patients with
      schizophrenia.
AB  - Disturbances in implicit self-processing have been reported both in psychotic
      patients with bipolar disorder (BD) and schizophrenia. It remains unclear whether
      these two psychotic disorders show disturbed functional connectivity during
      explicit self-reflection, which is associated with social functioning and illness
      symptoms. Therefore, we investigated functional connectivity during explicit self
      reflection in BD with past psychosis and schizophrenia. Twenty-three BD-patients,
      17 schizophrenia-patients and 21 health controls (HC) performed a self-reflection
      task, including the conditions self-reflection, close other-reflection and
      semantic control. Functional connectivity was investigated with generalized
      psycho-physiological interaction (gPPI). During self-reflection compared to
      semantic, BD-patients had decreased connectivity between several cortical-midline
      structures (CMS) nodes (i.e., anterior cingulate cortex, ventromedial prefrontal
      cortex), the insula and the head of the caudate while HC showed increased
      connectivities. Schizophrenia-patients, during close other-reflection compared to
      semantic, demonstrated reduced ventral-anterior insula-precuneus/posterior
      cingulate cortex (PCC) functional connectivity, whereas this was increased in HC.
      There were no differences between BD and schizophrenia during self- and close
      other-reflection. We propose that decreased functional connectivity between the
      CMS nodes/insula and head of the caudate in BD-patients may imply a reduced
      involvement of the motivational system during self-reflection; and the reduced
      functional connectivity between the ventral-anterior insula and precuneus/PCC
      during close other-reflection in schizophrenia-patients may subserve difficulties
      in information integration of autobiographical memory and emotional awareness in
      relation to close others. These distinctive impaired patterns of functional
      connectivity in BD and schizophrenia (compared to HC) deserve further
      investigation to determine their robustness and associations with differences in
      clinical presentation.

PMID- 27693669
TI  - Polymorphisms of Interlukin-1beta rs16944 confer susceptibility to
      myelodysplastic syndromes.
AB  - Genetic factors have been shown to be associated with Myelodysplastic syndromes
      (MDS) susceptibility. In recent years, the role of inflammation in the promotion
      of tumor growth is supported by a broad range of experimental and clinical
      evidence. But the relationship between polymorphisms in NOD-like receptor protein
      3 (NLRP3) inflammasome and MDS is rarely reported. Thus, we conducted a case
      control study, and genotyped five single nucleotide polymorphisms (SNPs) (NLRP3,
      IL-1beta, IL-18, CARD8, and NF-kappaB) in MDS patients and healthy controls. The
      association of different genotypes with patient characteristics was analyzed.
      Comparing MDS patients with controls, GG genotype of IL-1beta (rs16944) was
      observed to be associated with a significantly increased risk of MDS 78/166
      (48.8%) vs 26/96 (27.0%), OR=2.1, CI (1.0-4.4). No significant association was
      identified regarding the rest of investigated polymorphisms and MDS
      susceptibility. Complex karyotypes were more frequent in patients with GG
      genotype of IL-1beta (rs16944). Patients with IL-1beta polymorphisms (rs16944) GG
      and GA had lower hemoglobin than those without. Patients with IL-1beta
      polymorphisms (rs16944) GG had higher IPSS scores than those without IL-1beta
      polymorphisms. In conclusion, our present data shows that the IL-1beta
      polymorphisms (rs16944) GG were frequently occurred in MDS. IL-1beta (rs16944) GG
      genotype might serve as a novel biomarker and potential targets for MDS.

PMID- 27693670
TI  - [18F]Fluoro-azomycin-2'-deoxy-beta-d-ribofuranoside - A new imaging agent for
      tumor hypoxia in comparison with [18F]FAZA.
AB  - INTRODUCTION: Radiolabeled 2-nitroimidazoles (azomycins) are a prominent class of
      biomarkers for PET imaging of hypoxia. [18F]Fluoro-azomycin-alpha-arabinoside
      ([18F]FAZA) - already in clinical use - may be seen as alpha-configuration
      nucleoside, but enters cells only via diffusion and is not transported by
      cellular nucleoside transporters. To enhance image contrast in comparison to
      [18F]FAZA our objective was to 18F-radiolabel an azomycin-2'-deoxyriboside with
      beta-configuration ([18F]FAZDR, [18F]-beta-8) to mimic nucleosides more closely
      and comparatively evaluate it versus [18F]FAZA. METHODS: Precursor and cold
      standards for [18F]FAZDR were synthesized from methyl 2-deoxy-d-ribofuranosides
      alpha- and beta-1 in 6 steps yielding precursors alpha- and beta-5. beta-5 was
      radiolabeled in a GE TRACERlab FXF-N synthesizer in DMSO and deprotected with
      NH4OH to give [18F]FAZDR ([18F]-beta-8). [18F]FAZA or [18F]FAZDR was injected in
      BALB/c mice bearing CT26 colon carcinoma xenografts, PET scans (10min) were
      performed after 1, 2 and 3h post injection (p.i.). On a subset of mice injected
      with [18F]FAZDR, we analyzed biodistribution. RESULTS: [18F]FAZDR was obtained in
      non-corrected yields of 10.9+/-2.4% (9.1+/-2.2GBq, n=4) 60min EOB, with
      radiochemical purity >98% and specific activity >50GBq/MUmol. Small animal PET
      imaging showed a decrease in uptake over time for both [18F]FAZDR (1h p.i.:
      0.56+/-0.22% ID/cc, 3h: 0.17+/-0.08% ID/cc, n=9) and [18F]FAZA (1h: 1.95+/-0.59%
      ID/cc, 3h: 0.87+/-0.55% ID/cc), whereas T/M ratios were significantly higher for
      [18F]FAZDR at 1h (2.76) compared to [18F]FAZA (1.69, P<0.001), 3h p.i. ratios
      showed no significant difference. Moreover, [18F]FAZDR showed an inverse
      correlation between tracer uptake in carcinomas and oxygen breathing, while
      muscle tissue uptake was not affected by switching from air to oxygen.
      CONCLUSIONS: First PET imaging results with [18F]FAZDR showed advantages over
      [18F]FAZA regarding higher tumor contrast at earlier time points p.i.
      Availability of precursor and cold fluoro standard together with high output
      radiosynthesis will allow for a more detailed quantitative evaluation of
      [18F]FAZDR, especially with regard to mechanistic studies whether active
      transport processes are involved, compared to passive diffusion as observed for
      [18F]FAZA.

PMID- 27693671
TI  - Facile room temperature synthesis of fluorine-18 labeled fluoronicotinic acid
      2,3,5,6-tetrafluorophenyl ester without azeotropic drying of fluorine-18.
AB  - Fluorine-18 labeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester has been
      successfully synthesized in an unprecedented way by flowing an acetonitrile
      solution of its quaternary ammonium salt precursor (N,N,N-trimethyl-5-((2,3,5,6
      tetrafluorophenoxy)carbonyl)pyridin-2-aminium trifluoromethanesulfonate, 1)
      through an anion exchange cartridge. The fluorination reaction proceeded at room
      temperature without azeotropic drying of the fluoride. Over 75% conversion was
      observed with 10mg of precursor in 2:8, acetonitrile: t-butanol in 1min. The
      total synthesis time was 5min which is ~30min shorter than the current literature
      method.

PMID- 27693673
TI  - A Conserved Interaction between SKIP and SMP1/2 Aids in Recruiting the Second
      Step Splicing Factors to the Spliceosome in Arabidopsis.

PMID- 27693672
TI  - [18F]MEL050 as a melanin-targeted PET tracer: Fully automated radiosynthesis and
      comparison to 18F-FDG for the detection of pigmented melanoma in mice primary
      subcutaneous tumors and pulmonary metastases.
AB  - INTRODUCTION: Melanoma is a highly malignant cutaneous tumor of melanin-producing
      cells. MEL050 is a synthetic benzamide-derived molecule that specifically binds
      to melanin with high affinity. Our aim was to implement a fully automated
      radiosynthesis of [18F]MEL050, using for the first time, the AllInOneTM synthesis
      module (Trasis), and to evaluate the potential of [18F]MEL050 for the detection
      of pigmented melanoma in mice primary subcutaneous tumors and pulmonary
      metastases, and to compare it with that of [18F]FDG. METHODS: Automated
      radiosynthesis of [18F]MEL050, including HPLC purification and formulation, were
      performed on an AllInOneTM synthesis module. [18F]MEL050 was synthesized using a
      one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma
      models were induced by subcutaneous (primary tumor) or intravenous (pulmonary
      metastases) injection of B16-F10-luc2 cells in NMRI mice. The maximum percentage
      of [18F]MEL050 Injected Dose per g of lung tissue (%ID/g Max) was determined on
      PET images, compared to [18F]FDG and correlated to in vivo bioluminescence
      imaging. RESULTS: The automated radiosynthesis of [18F]MEL050 required an overall
      radiosynthesis time of 48min, with a yield of 13-18% (not-decay corrected) and
      radiochemical purity higher than 99%. [18F]MEL050 PET/CT images were concordant
      with bioluminescence imaging, showing increased radiotracer uptake in all primary
      subcutaneous tumors and pulmonary metastases of mice. PET quantification of
      radiotracers uptake in tumors and muscles demonstrated similar tumor-to
      background ratio (TBR) with [18F]MEL050 and [18F]FDG in subcutaneous tumors and
      higher TBR with [18F]MEL050 than with [18F]FDG in pulmonary metastases.
      CONCLUSION: We successfully implemented the radiosynthesis of [18F]MEL050 using
      the AllInOneTM module, including HPLC purification and formulation. In vivo
      PET/CT validation of [18F]MEL050 was obtained in mouse models of pigmented
      melanoma, where higher [18F]MEL050 uptake was observed in sub-millimetric
      pulmonary metastases, comparatively to [18F]FDG.

PMID- 27693674
TI  - PGRL1 and LHCSR3 Compensate for Each Other in Controlling Photosynthesis and
      Avoiding Photosystem I Photoinhibition during High Light Acclimation of
      Chlamydomonas Cells.

PMID- 27693675
TI  - The Dark Side of the Genome: Revealing the Native Transposable Element/Repeat
      Content of Eukaryotic Genomes.

PMID- 27693676
TI  - Correlation among chemical structure, surface properties and cytotoxicity of N
      acyl alanine and serine surfactants.
AB  - Toxicity is one of the main concerns limiting the use of surfactants. Many
      efforts have been devoted to the development of new amphiphilic molecules
      characterized by a lower toxicological profile and environmental impact. N-acyl
      amino acids are a class of anionic surfactants that can find applications in
      different technological fields as an alternative to sulphate-based surfactants
      (e.g., sodium dodecyl sulphate). The understanding of the relationship between
      chemical structure and toxicological profile is fundamental for the disclosure of
      the full potential of these amphiphiles. With this aim, two series of N-acyl
      surfactants, with different length of the hydrophobic tails and serine or alanine
      as polar head, were synthesized and fully characterized. The correlation between
      the surface and toxicological parameters allowed highlighting the role exerted by
      the length of the hydrocarbon chain and the polar head on cytotoxicity. The
      length of the hydrocarbon chain mainly influences surface properties and
      toxicological parameters, while the amino acid polar head may play a key role
      only on cellular toxicity. Overall, our data suggest that minor differences in
      the polar head, not significantly affecting CMC values, may have an impact on
      cytotoxicity.

PMID- 27693677
TI  - Development, in vitro and in vivo evaluation of a self-emulsifying drug delivery
      system (SEDDS) for oral enoxaparin administration.
AB  - AIM: The aim of this study was to develop SEDDS for oral enoxaparin
      administration and evaluate it in vitro and in vivo. METHODS: The emulsifying
      properties of SEDDS composed of long chain lipids (LC-SEDDS), medium chain lipids
      (MC-SEDDS), short chain lipids (SC-SEDDS) and no lipids (NL-SEDDS) were
      evaluated. Thereafter, enoxaparin was incorporated via hydrophobic ion pairing in
      the chosen SEDDS, which were evaluated regarding their mucus permeating
      properties, stability towards pancreatic lipase, drug release profile and
      cytotoxicity. Finally, in vivo performance of SEDDS was evaluated. RESULTS: The
      average droplet size of chosen LC-SEDDS, MC-SEDDS and NL-SEDDS ranged between 30
      and 40nm. MC-SEEDS containing 30% Captex 8000, 30% Capmul MCM, 30% Cremophor EL
      and 10% propylene glycol and NL-SEDDS containing 31.5% Labrafil 1944, 22.5%
      Capmul PG-8, 9% propylene glycol, 27% Cremophor EL and 10% DMSO exhibited 2-fold
      higher mucus diffusion than LC-SEDDS and were therefore chosen for further
      studies. The enoxaparin-dodecylamine complex (ENOX/DOA) was incorporated in a
      payload of 2% (w/w) into MC-SEDDS and NL-SEDDS. After 90min 97% of MC-SEDDS and
      5% of NL-SEDDS were degraded by pancreatic lipase. Both MC-SEDDS and NL-SEDDS
      showed sustained in vitro enoxaparin release. Furthermore, orally administrated
      MC-SEDDS and NL-SEDDS yielded an absolute enoxaparin bioavailability of 2.02% and
      2.25%, respectively. CONCLUSION: According to the abovementioned findings, SEDDS
      could be considered as a potential oral LMWH delivery system.

PMID- 27693678
TI  - Gastrointestinal dissolution, supersaturation and precipitation of the weak base
      indinavir in healthy volunteers.
AB  - This study investigated the impact of relevant gastrointestinal conditions on the
      intraluminal dissolution, supersaturation and precipitation behavior of the
      weakly basic drug indinavir. The influence of (i) concomitant PPI intake and (ii)
      the nutritional state on the gastrointestinal behavior of indinavir was assessed
      in order to identify the underlying mechanisms responsible for previously
      reported interactions. Five healthy volunteers were recruited into a crossover
      study containing the following arms: fasted state, fed state and fasted state
      with concomitant proton pump inhibitor (PPI) use. In each condition, one
      Crixivan(r) capsule (400mg indinavir) was orally administered with 240mL of
      water. Gastric and duodenal fluids, aspirated as a function of time, were
      monitored for total and dissolved indinavir concentrations on a UPLC-MS/MS
      system. Indinavir's thermodynamic solubility was determined in individual
      aspirates to evaluate supersaturation. The bioaccessible fraction of indinavir in
      aspirated duodenal fluids was determined in an ex vivo permeation experiment
      through an artificial membrane. A nearly complete dissolution of indinavir in the
      fasted stomach was observed (90+/-3%). Regardless of dosing conditions, less
      indinavir was in solution in the duodenum compared to the stomach. Duodenal
      supersaturation was observed in all three testing conditions. The highest degrees
      of duodenal supersaturation (6.5+/-5.9) were observed in the fasted state.
      Concomitant PPI use resulted in an increased gastric pH and a smaller fraction of
      indinavir being dissolved (58+/-24%), eventually resulting in lower intestinal
      concentrations. In fed state conditions, drug release from the capsule was
      delayed and more gradually, although a similar fraction of the intragastric
      indinavir dissolved compared to the fasted state (83+/-12%). Indinavir was still
      present in the lumen of the duodenum three hours after oral administration,
      although it already reached 70% (on average) of the fasted state concentrations
      (expressed as AUC0-3h). Based on a 2-h permeation experiment, the bioaccessible
      fraction of indinavir was 2.6-fold lower in a fed state sample compared to a
      fasted state sample. Our data indicate that the reported reduction in indinavir's
      bioavailability after concomitant PPI administration is caused by an elevated
      gastric pH resulting in less indinavir in solution in the stomach and,
      subsequently, reduced duodenal concentrations. In fed state conditions, however,
      intestinal micellar entrapment of indinavir appeared to cause the reported
      reduced bioavailability, regardless of duodenal concentrations.

PMID- 27693679
TI  - Zinc peroxide nanomaterial as an adsorbent for removal of Congo red dye from
      waste water.
AB  - In the past decade, various natural byproducts, advanced metal oxide composites
      and photocatalysts have been reported for removal of dyes from water. Although
      these materials are useful for select applications, they have some limitations
      such as use at fixed temperature, ultra violet (UV) light and the need for
      sophisticated experimental set up. These materials can remove dyes up to a
      certain extent but require long time. To overcome these limitations, a promising
      adsorbent zinc peroxide (ZnO2) nanomaterial has been developed for the removal of
      Congo red (CR) dye from contaminated water. ZnO2 is highly efficient even in the
      absence of sunlight to remove CR from contaminated water upto the permissible
      limits set by the World Health Organization (WHO) and the United States-
      Environmental Protection Agency (US-EPA). The adsorbent has a specific property
      to adjust the pH of the test solution within 6.5-7.5 range irrespective of acidic
      or basic nature of water. The adsorption capacity of the material for CR dye was
      208mgg-1 within 10min at 2-10pH range. The proposed material could be useful for
      the industries involved in water purification. The removal of CR has been
      confirmed by spectroscopic and microscopic techniques. The adsorption data
      followed a second order kinetics and Freundlich isotherm.

PMID- 27693682
TI  - Moose Antler Sign, a Sign of Deep Endometriosis Infiltrating Bowel.

PMID- 27693681
TI  - Do No Harm, Except to Ourselves? A Survey of Symptoms and Injuries in Oncologic
      Surgeons and Pilot Study of an Intraoperative Ergonomic Intervention.
AB  - BACKGROUND: Occupational symptoms and injuries incurred over a surgical career
      are under- reported, yet they have an impact on daily surgical practice. We
      assessed the frequency, consequences, and risk factors for occupational injury in
      oncologic surgeons and evaluated the feasibility of intraoperative foot mat use
      to mitigate occupational symptoms. STUDY DESIGN: Oncologic surgeons completed a
      survey of demographic information and occupational symptoms and injuries.
      Multivariate logistic regression was used to identify factors associated with
      occupational symptoms and injuries. A randomized cross-over pilot study of
      intraoperative foot mat use was conducted. RESULTS: One hundred twenty-seven
      surgeons completed surveys (response rate: 58%). The most commonly reported
      symptoms were fatigue, discomfort, stiffness, and back pain. An occupational
      injury was reported by 27.6% of surgeons. Of those injured, 65.7% received
      treatment, with 17.4% of those treated requiring surgery for their injury. In
      multivariate analysis, factors significantly associated with occupational injury
      were male sex (odds ratio [OR] 3.00, 95% CI 1.08 to 8.38), mean case length of 4
      hours or more (OR 2.72, 95% CI 1.08 to 6.87), using a step to operate (OR 3.06,
      95% CI 1.02 to 9.15), and neck pain (OR 4.81, 95% CI 1.64 to 14.12). In the foot
      mat pilot study (n = 20), mat use was associated with discomfort (OR 7.57, 95% CI
      1.19 to 48.00), but no significant differences in leg volume change due to mat
      use were found. CONCLUSIONS: Most oncologic surgeons experience musculoskeletal
      symptoms from operating. Of the 28% of surgeons with an occupational injury, most
      required treatment. Intraoperative foot mat use was associated with increased
      discomfort.

PMID- 27693680
TI  - Cadmium stress tolerance in wheat seedlings induced by ascorbic acid was mediated
      by NO signaling pathways.
AB  - Ascorbic acid (AsA) and nitric oxide (NO) are well known and widespread
      antioxidants and gaseous molecules that regulate plant tolerance to several
      stresses. However, the relationship between them in plant response to stress,
      especially heavy stress, is largely unclear. This study demonstrated that both
      AsA and NO could enhance the tolerance of wheat seedlings to cadmium stress
      evidenced by root length change, which resulted from their roles in maintaining
      the balance in reactive oxygen species (ROS) and reducing the absorption of Cd.
      Furthermore, exogenous AsA led to a significant increase of NO content and
      endogenous AsA content in wheat roots, which could be weakened by the NO
      scavenger c-PTIO. In addition, c-PTIO also inhibits the NO-induced production of
      endogenous AsA. Although the AsA synthesis inhibitor lycorine significantly
      inhibited the inductive effect of exogenous AsA on endogenous AsA production, it
      has little effect on NO content. In addition, we found that the protective
      effects of NO and AsA on Cd stress were removed by c-PTIO and lycorine. These
      results indicated that NO accumulation could be necessary for exogenous AsA
      induced cadmium tolerance and endogenous AsA production, and the exogenous AsA
      induced endogenous AsA production was likely mediated by NO signaling pathways
      and together they induced the tolerance of wheat to cadmium stress.

PMID- 27693683
TI  - Endometriotic Vaginal Vault Nodule Causing Posthysterectomy Vaginal Bleeding.

PMID- 27693684
TI  - Auditory steady-state responses as neural correlates of loudness growth.
AB  - The aim of this study was to find an objective estimate of individual, complete
      loudness growth functions based on auditory steady-state responses. Both normal
      hearing and hearing-impaired listeners were involved in two behavioral loudness
      growth tasks and one EEG recording session. Behavioral loudness growth was
      measured with Absolute Magnitude Estimation and a Graphic Rating Scale with
      loudness categories. Stimuli were sinusoidally amplitude-modulated sinusoids with
      carrier frequencies of either 500 Hz or 2000 Hz, a modulation frequency of 40 Hz,
      a duration of 1 s, and presented at intensities encompassing the participants'
      dynamic ranges. Auditory steady-state responses were evoked by the same stimuli
      using durations of at least 5 min. Results showed that there was a good
      correspondence between the relative growth of the auditory steady-state response
      amplitudes and the behavioral loudness growth responses for each participant of
      both groups of listeners. This demonstrates the potential for a more individual,
      objective, and automatic fitting of hearing aids in future clinical practice.

PMID- 27693685
TI  - The granulocytes are the main immunocompetent hemocytes in Crassostrea gigas.
AB  - Hemocytes comprise diverse cell types with morphological and functional
      heterogeneity and play indispensable roles in immunological homeostasis of
      invertebrates. The morphological classification of different hemocytes in mollusk
      has been studied since the 1970's, yet the involvement of the different sub
      populations in immune functions is far from clear. In the present study, three
      types of hemocytes were morphologically identified and separated as
      agranulocytes, semi-granulocytes and granulocytes by flow cytometry and
      Percoll(r) density gradient centrifugation. The granulocytes were characterized
      functionally as the main phagocytic and encapsulating population, while semi
      granulocytes and agranulocytes exhibited low or no such capacities, respectively.
      Meanwhile, the lysosome activity and the productions of ROS and NO were all
      mainly concentrated in granulocytes under both normal and immune-activated
      situations. Further, the mRNA transcripts of some immune related genes, including
      CgTLR, CgClathrin, CgATPeV, CgLysozyme, CgDefensin and CgIL-17, were mainly
      expressed in granulocytes, lower in semi-granulocytes and agranulocytes. These
      results collectively suggested that the granulocytes were the main
      immunocompetent hemocytes in oyster C. gigas, and a differentiation relationship
      among these three sub-population hemocytes was inferred based on the gradual
      changes in morphological, functional and molecular features.

PMID- 27693686
TI  - Gold-nanoparticles coated with the antimicrobial peptide esculentin-1a(1-21)NH2
      as a reliable strategy for antipseudomonal drugs.
AB  - : Naturally occurring antimicrobial peptides (AMPs) hold promise as future
      therapeutics against multidrug resistant microorganisms. Recently, we have
      discovered that a derivative of the frog skin AMP esculentin-1a, Esc(1-21), is
      highly potent against both free living and biofilm forms of the bacterial
      pathogen Pseudomonas aeruginosa. However, bringing AMPs into clinics requires to
      overcome their low stability, high toxicity and inefficient delivery to the
      target site at high concentrations. Importantly, peptide conjugation to gold
      nanoparticles (AuNPs), which are among the most applied inorganic nanocarriers in
      biomedical sciences, represents a valuable strategy to solve these problems. Here
      we report that covalent conjugation of Esc(1-21) to soluble AuNPs [AuNPs@Esc(1
      21)] via a poly(ethylene glycol) linker increased by ~15-fold the activity of the
      free peptide against the motile and sessile forms of P. aeruginosa without being
      toxic to human keratinocytes. Furthermore, AuNPs@Esc(1-21) resulted to be
      significantly more resistant to proteolytic digestion and to disintegrate the
      bacterial membrane at very low concentration (5nM). Finally, we demonstrated for
      the first time the capability of peptide-coated AuNPs to display a wound healing
      activity on a keratinocytes monolayer. Overall, these findings suggest that our
      engineered AuNPs can serve as attractive novel biological-derived material for
      topical treatment of epithelial infections and healing of the injured tissue.
      STATEMENT OF SIGNIFICANCE: Despite conjugation of AMPs to AuNPs represents a
      worthwhile solution to face some limitations for their development as new
      therapeutics, only a very limited number of studies is available on peptide
      coated AuNPs. Importantly, this is the first report showing that a covalent
      binding of a linear AMP via a poly(ethylene glycol) linker to AuNPs highly
      enhances antipseudomonal activity, preserving the same mode of action of the free
      peptide, without being harmful. Furthermore, AuNPs@Esc(1-21) are expected to
      accelerate recovery of an injured skin layer. All together, these findings
      suggest our peptide-coated AuNPs as attractive novel nanoscale formulation to
      treat bacterial infections and to heal the injured tissue.

PMID- 27693687
TI  - Comparing the microstructure and mechanical properties of Bombyx mori and
      Antheraea pernyi cocoon composites.
AB  - : Silkworm cocoon material is a natural composite consisting of silk fibres and
      sericin glues. Both domestic and wild silkworms produce cocoons but with
      different functionality - one selected by man for textile manufacture whereas the
      other selected by Nature to provide damage-tolerant housing. To understand the
      structure--property relationship of cocoons, we evaluated and compared the
      microstructure and mechanical properties of two representative cocoon walls. It
      appears that a "brittle and weak" composite is produced by domestic Bombyx mori
      (B. mori) while a "tough and strong" composite is made by wild Antheraea pernyi
      (A. pernyi). The superior mechanical performance of A. pernyi cocoons can be
      attributed to both the material properties and the fibre network microstructures.
      Failure mechanisms and different failure modes for cocoon fibre composites were
      also proposed. A finite element model revealed qualitatively the effect of fibre
      properties and inter-fibre bonding strength on the mechanical properties of the
      fibre network. It emerged that both good mechanical properties of fibres and
      robust inter-fibre bonding were required for tough and strong fibre composites.
      The new insights could inspire new designs of synthetic fibre composites with
      enhanced mechanical properties. STATEMENT OF SIGNIFICANCE: Natural cocoons are an
      important group of natural fibre composites with versatile functionalities.
      Previous studies have focused on the diversity of cocoon species and different
      morphological and mechanical features. It was suggested that the cocoon network
      structure determined the final mechanical properties of the cocoon composite.
      Nevertheless, the full structure-propertyfunction relationships for the cocoon
      composite are not understood. By studying two distinct cocoon species with
      specific functionalities, we prove that the mechanical properties of two cocoons
      are determined by both network properties and fibre properties. A robust fibre
      network is the prerequisite, within which the good mechanical properties of the
      fibres can play a part. The finding will inspire new designs of synthetic
      composites with desirable and predictable mechanical properties.

PMID- 27693688
TI  - Modular peptides from the thermoplastic squid sucker ring teeth form amyloid-like
      cross-beta supramolecular networks.
AB  - : The hard sucker ring teeth (SRT) from decapodiforme cephalopods, which are
      located inside the sucker cups lining the arms and tentacles of these species,
      have recently emerged as a unique model structure for biomimetic structural
      biopolymers. SRT are entirely composed of modular, block co-polymer-like proteins
      that self-assemble into a large supramolecular network. In order to unveil the
      molecular principles behind SRT's self-assembly and robustness, we describe a
      combinatorial screening assay that maps the molecular-scale interactions between
      the most abundant modular peptide blocks of suckerin proteins. By selecting
      prominent interaction hotspots from this assay, we identified four peptides that
      exhibited the strongest homo-peptidic interactions, and conducted further in
      depth biophysical characterizations complemented by molecular dynamic (MD)
      simulations to investigate the nature of these interactions. Circular Dichroism
      (CD) revealed conformations that transitioned from semi-extended poly-proline II
      (PII) towards beta-sheet structure. The peptides spontaneously self-assembled
      into microfibers enriched with cross beta-structures, as evidenced by Fourier
      Transform Infrared Spectroscopy (FTIR) and Congo red staining. Nuclear Magnetic
      Resonance (NMR) experiments identified the residues involved in the hydrogen
      bonded network and demonstrated that these self-assembled beta-sheet-based fibers
      exhibit high protection factors that bear resemblance to amyloids. The high
      stability of the beta-sheet network and an amyloid-like model of fibril assembly
      were supported by MD simulations. The work sheds light on how Nature has evolved
      modular sequence design for the self-assembly of mechanically robust functional
      materials, and expands our biomolecular toolkit to prepare load-bearing
      biomaterials from protein-based block co-polymers and self-assembled peptides.
      STATEMENT OF SIGNIFICANCE: The sucker ring teeth (SRT) located on the arms and
      tentacles of cephalopods represent as a very promising protein-based biopolymer
      with the potential to rival silk in biomedical and engineering applications. SRT
      are made of modular, block co-polymer like proteins (suckerins), which assemble
      into a semicrystalline polymer reinforced by nano-confined beta-sheets, resulting
      in a supramolecular network with mechanical properties that match those of the
      strongest engineering polymers. In this study, we aimed to understand the
      molecular mechanisms behind SRT's self-assembly and robustness. The most abundant
      modular peptidic blocks of suckerin proteins were studied by various
      spectroscopic methods, which demonstrate that SRT peptides form amyloid-like
      cross-beta structures.

PMID- 27693689
TI  - Development of multifunctional films for peripheral nerve regeneration.
AB  - : In this study, a poly(lactic acid) (PLLA) porous film with longitudinal surface
      micropatterns was fabricated by a dry phase inversion technique to be used as
      potential conduit material for peripheral nerve regeneration applications. The
      presence of a nerve growth factor (NGF) gradient on the patterned film surface
      and protein loaded, surface-eroding, biodegradable, and amphiphilic polyanhydride
      (PA) microparticles within the film matrix, enabled co-delivery of neurotrophic
      factors with controlled release properties and enhanced neurite outgrowth from
      PC12 cells. The protein loading capacity of PA particles was increased up to 80%
      using the spray drying technique, while the surface loading of NGF reached
      300ng/cm2 through ester-amine interactions. The NGF surface gradient provided
      initial fast release from the film surface and facilitated directional neurite
      outgrowth along with the longitudinal micropatterns. Furthermore, the variable
      backbone chemistry and surface eroding nature of protein-loaded PA microparticles
      within the film matrix ensured protein stability and enabled controlled protein
      release. This novel co-delivery strategy yielded tunable diffusion coefficients
      varying between 6*10-14 and 1.67*10-10cm2/min and dissolution constants ranging
      from 1*10-4 to 1*10-3min-1 with released amounts of ~100-300ng/mL. This strategy
      promoted guided neurite extension from PC12 cells of up to 10MUm total neurite
      length per cell in 2days. Overall, this unique strategy can potentially be
      extended for individually programmed delivery of multiple growth factors through
      the use of PA microparticle cocktails and can further be investigated for in vivo
      performance as potential conduit material for peripheral nerve regeneration
      applications. STATEMENT OF SIGNIFICANCE: This manuscript focuses on the
      development of multifunctional degradable polymer films that provide topographic
      cues for guided growth, surface gradients of growth factors as well as
      nanoparticles in the films for tunable release of growth factors to enable
      peripheral nerve regeneration. The combination of cues was designed to overcome
      limitations of current strategies to facilitate peripheral nerve regeneration.
      These multifunctional films successfully provided high protein loading capacities
      while persevering activity, protein gradients on the surface, and tunable release
      of bioactive nerve growth factor that promoted directional and guided neurite
      extension of PC12 cells of up to 10MUm in 2days. These multifunctional films can
      be made into conduits for peripheral nerve regeneration.

PMID- 27693691
TI  - Muscle Activation During Pilates Exercises in Participants With Chronic
      Nonspecific Low Back Pain: A Cross-Sectional Case-Control Study.
AB  - OBJECTIVE: To determine the amplitude of the electromyographic activity of trunk
      muscles during Pilates exercises in women with and without chronic low back pain
      (LBP). DESIGN: Case-control study. SETTING: University physical therapy clinic.
      PARTICIPANTS: Women (N=60) divided into an LBP group and a control group.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Amplitude of the
      electromyographic activity (root mean square values) of the gluteus maximus and
      external oblique muscles collected during 3 Pilates exercises: Shoulder Bridge
      performed on the mat, and Hip Roll and Breathing performed in equipment. Pain
      intensity was assessed in the LBP group. RESULTS: The amplitude of the
      electromyographic activity was similar between groups (P>=.05). For both groups,
      the amplitude of the gluteus maximus was higher in the Shoulder Bridge exercise
      compared with the Hip Roll with 2 springs (control group: mean difference
      [MD]=.18; 95% confidence interval [CI], .05-.41; LBP group: MD=.29; 95% CI, .16
      .31) and the Breathing exercise (control group: MD=-.40; 95% CI, -.55 to -.26;
      LBP group: MD=-.36; 95% CI, -.52 to -.20). The amplitude of the external oblique
      muscle was higher in the Shoulder Bridge compared with the Hip Roll with 2
      springs (control group: MD=.13; 95% CI, .05-.21; LBP group: MD=.18; 95% CI, .03
      .33). Pain intensity increased after exercises, but this increase was lower for
      the mat exercises. CONCLUSIONS: Similar muscle activation between groups was
      found. The findings suggest that mat exercises caused less pain and a greater
      difference in the amplitude of muscle activation compared with the equipment
      based exercises.

PMID- 27693690
TI  - Targeted proteomics effectively quantifies differences between native lung and
      detergent-decellularized lung extracellular matrices.
AB  - : Extracellular matrix is a key component of many products in regenerative
      medicine. Multiple regenerative medicine products currently in the clinic are
      comprised of human or xenogeneic extracellular matrix. In addition, whole-organ
      regeneration exploits decellularized native organs as scaffolds for organotypic
      cell culture. However, precise understanding of the constituents of such
      extracellular matrix-based implants and scaffolds has sorely lagged behind their
      use. We present here an advanced protein extraction method using known quantities
      of proteotypic 13C-labeled peptides to quantify matrix proteins in native and
      decellularized lung tissues. Using quantitative proteomics that produce picomole
      level measurements of a large number of matrix proteins, we show that a mild
      decellularization technique ("Triton/SDC") results in near-native retention of
      laminins, proteoglycans, and other basement membrane and ECM-associated proteins.
      Retention of these biologically important glycoproteins and proteoglycans is
      quantified to be up to 27-fold higher in gently-decellularized lung scaffolds
      compared to scaffolds generated using a previously published decellularization
      regimen. Cells seeded onto this new decellularized matrix also proliferate
      robustly, showing positive staining for proliferating cell nuclear antigen
      (PCNA). The high fidelity of the gently decellularized scaffold as compared to
      the original lung extracellular matrix represents an important step forward in
      the ultimate recapitulation of whole organs using tissue-engineering techniques.
      This method of ECM and scaffold protein analysis allows for better understanding,
      and ultimately quality control, of matrices that are used for tissue engineering
      and human implantation. These results should advance regenerative medicine in
      general, and whole organ regeneration in particular. STATEMENT OF SIGNIFICANCE:
      The extracellular matrix (ECM) in large part defines the biochemical and
      mechanical properties of tissues and organs; these inherent cues make acellular
      ECM scaffolds potent substrates for tissue regeneration. As such, they are
      increasingly prevalent in the clinic and the laboratory. However, the exact
      composition of these scaffolds has been difficult to ascertain. This paper uses
      targeted proteomics to definitively quantify 71 proteins present in acellular
      lung ECM scaffolds. We use this technique to compare two decellularization
      methods and demonstrate superior retention of ECM proteins important for cell
      adhesion, migration, proliferation, and differentiation in scaffolds treated with
      low-concentration detergent solutions. In the long term, the ability to acquire
      quantitative biochemical data about biological substrates will facilitate the
      rational design of engineered tissues and organs based on precise cell-matrix
      interactions.

PMID- 27693692
TI  - 5-Aminolevulinic acid with sodium ferrous citrate induces autophagy and protects
      cardiomyocytes from hypoxia-induced cellular injury through MAPK-Nrf-2-HO-1
      signaling cascade.
AB  - BACKGROUND: Hypoxia causes cardiac disease via oxidative stress and mitochondrial
      dysfunction. 5-Aminolevulinic acid in combination with sodium ferrous citrate
      (ALA/SFC) has been shown to up-regulate heme oxygenase-1 (HO-1) and decrease
      macrophage infiltration and renal cell apoptosis in renal ischemia injury mice.
      However, its underlying mechanism remains largely unknown. The aim of this study
      was to investigate whether ALA/SFC could protect cardiomyocytes from hypoxia
      induced apoptosis by autophagy via HO-1 signaling. MATERIALS & METHODS: Murine
      atrial cardiomyocyte HL-1 cells were pretreated with ALA/SFC and then exposed to
      hypoxia. RESULTS: ALA/SFC pretreatment significantly attenuated hypoxia-induced
      cardiomyocyte apoptosis, reactive oxygen species production, and mitochondrial
      injury, while it increased cell viability and autophagy levels. HO-1 expression
      by ALA/SFC was associated with up-regulation and nuclear translocation of Nrf-2,
      whereas Nrf-2 siRNA dramatically reduced HO-1 expression. ERK1/2, p38, and
      SAPK/JNK pathways were activated by ALA/SFC and their specific inhibitors
      significantly reduced ALA/SFC-mediated HO-1 upregulation. Silencing of either Nrf
      2 or HO-1and LY294002, inhibitor of autophagy, abolished the protective ability
      of ALA/AFC against hypoxia-induced injury and reduced ALA/SFC-induced autophagy.
      CONCLUSION: Taken together, our data suggest that ALA/SFC induces autophagy via
      activation of MAPK/Nrf-2/HO-1 signaling pathway to protect cardiomyocytes from
      hypoxia-induced apoptosis.

PMID- 27693693
TI  - Lumican alleviates hypertrophic scarring by suppressing integrin-FAK signaling.
AB  - Hypertrophic scarring (HS) is an overcompensation of wound healing that increases
      the risk of cosmetic disfigurement and functional impairment. No gold standard
      has been established for the treatment or prevention of HS. Our study aims to
      elucidate the expression and function of lumican in the pathogenesis of HS as
      well as the underlying mechanism involved in this procedure. An animal model of
      HS (rabbit ear) was established, and the Ad-lumican vectors were locally
      injected. Primary fibroblasts isolated from patients with hypertrophic burn scars
      were used in vitro. Histological and molecular changes in HS pathogenesis were
      evaluated. The results showed that lumican is significantly reduced in HS tissues
      and fibroblasts from HS patients as compared to normal skin or cells. Lumican
      levels were further suppressed in response to TGF-beta stimulation. However,
      lumican upregulation effectively thinned the scar area and inhibited fibroblast
      proliferation and the cell cycle. Meanwhile, Ad-lumican administration suppressed
      the deposition of extracellular matrix, such as collagen and CTGF. Ad-lumican
      injected animals or fibroblasts presented comparable integrin alpha2beta1
      expression while greatly reduced phosphorylation of FAK compared to the negative
      control. Moreover, Ad-lumican administration largely enhanced the binding of
      lumican to integrin alpha2beta1 and may thus inhibit the signaling propagation of
      collagen-integrin alpha2beta1. Overall, the restoration of lumican levels
      contributed to suppressing the HS progression by inhibiting collagen-integrin
      alpha2beta1-FAK signaling.

PMID- 27693694
TI  - Progressive hearing loss and degeneration of hair cell stereocilia in taperin
      gene knockout mice.
AB  - The TPRN gene encodes taperin, which is prominently present at the taper region
      of hair cell stereocilia. Mutations in TPRN have been reported to cause autosomal
      recessive nonsyndromic deafness 79(DFNB 79). To investigate the role of taperin
      in pathogenesis of hearing loss, we generated TPRN knockout mice using TALEN
      technique. Sanger sequencing confirmed an 11 bp deletion at nucleotide 177-187 in
      exon 1 of TPRN, which results in a truncated form of taperin protein.
      Heterozygous TPRN+/- mice showed apparently normal auditory phenotypes to their
      wide-type (WT) littermates. Homozygous TPRN-/- mice exhibited progressive
      sensorineural hearing loss as reflected by auditory brainstem response to both
      click and tone burst stimuli at postnatal days 15 (P15), 30 (P30), and 60 (P60).
      Alex Fluor-594 phalloidin labeling showed no obvious difference in hair cell
      numbers in the cochlea between TPRN-/- mice and WT mice under light microscope.
      However, scanning electronic microscopy revealed progressive degeneration of
      inner hair cell stereocilia, from apparently normal at postnatal days 3 (P3) to
      scattered absence at P15 and further to substantial loss at P30. The outer hair
      cell stereocilia also showed progressive degeneration, though much less severe,
      Collectively, we conclude that taperin plays an important role in maintenance of
      hair cell stereocilia. Establishment of TPRN knockout mice enables further
      investigation into the function of this gene.

PMID- 27693695
TI  - Blocking CXCR7-mediated adipose tissue macrophages chemotaxis attenuates insulin
      resistance and inflammation in obesity.
AB  - Adipose tissue macrophages (ATMs) have been considered to have a pivotal role in
      the chronic inflammation development during obesity. Although chemokine-chemokine
      receptor interaction has been studied in ATMs infiltration, most chemokine
      receptors remain incompletely understood and little is known about their
      mechanism of actions that lead to ATMs chemotaxis and pathogenesis of insulin
      resistance during obesity. In this study, we reported that CXCR7 expression is
      upregulated in adipose tissue, and specifically in ATMs during obesity. In
      addition, CXCL11 or CXCL12-induced ATMs chemotaxis is mediated by CXCR7 in
      obesity but not leanness, whereas CXCR3 and CXCR4 are not involved. Additional
      mechanism study shows that NF-kappaB activation is essential in ATMs chemotaxis,
      and manipulates chemotaxis of ATMs via CXCR7 expression regulation in obesity.
      Most importantly, CXCR7 neutralizing therapy dose dependently leads to less
      infiltration of macrophages into adipose tissue and thus reduces inflammation and
      improves insulin sensitivity in obesity. In conclusion, these findings
      demonstrated that blocking CXCR7-mediated ATMs chemotaxis ameliorates insulin
      resistance and inflammation in obesity.

PMID- 27693696
TI  - NLRP2 is highly expressed in a mouse model of ischemic stroke.
AB  - Nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) are a class
      of cytoplasmic pattern-recognition receptors with a major role in innate
      immunity. Fourteen of the twenty-two human NLRs contain a pyrin domain and form
      the NLRP subfamily (NLRPs). Among NLRPs, NLRP2 is less well-understood in aspects
      of distribution and functions, especially in central nervous system (CNS). This
      study was the first to explore the expression of NLRP2 in central nervous system
      both under normal conditions and in ischemic stroke models. We found NLRP2
      protein had a basal level of expression in CNS, mainly in astrocytes and was
      significantly elevated in ischemic brains in vivo or oxygen-glucose deprivation
      treated cells in vitro. And silencing of NLRP2 genes could reduce the apoptotic
      rate of oxygen-glucose deprivation-treated cells. Thus high expression of NLRP2,
      especially in astrocytes, may play important roles in the pathophysiological
      process of ischemic stroke and has potential clinical value for the treatment of
      ischemic stroke.

PMID- 27693697
TI  - Let-7d miRNA prevents TGF-beta1-induced EMT and renal fibrogenesis through
      regulation of HMGA2 expression.
AB  - TGF-beta1-induced epithelial to mesenchymal transition (EMT) process of tubular
      epithelial cells plays a leading role in the occurrence and progression of renal
      fibrosis as seen in diabetic nephropathy (DN). High mobility group AT-hook 2
      (HMGA2) is considered to be involved in TGF-beta1-mediated EMT via multifactorial
      mechanisms. Specific microRNAs (miRNAs) are closely associated with EMT, and here
      we focused on let-7d miRNA as a regulator of HMGA2. This study aims to
      investigate the effects of HMGA2 on EMT process induced by TGF-beta1 using small
      interfering RNA (siRNA) technique in vitro, and further explore the potential
      role of let-7d miRNA during renal fibrosis in DN. We demonstrated that siRNA
      targeting HMGA2 was sufficient to inhibit TGF-beta1-induced EMT and fibrogenesis
      in rat kidney tubular epithelial cells (NRK52E). Furthermore, let-7d expression
      was significantly reduced by TGF-beta1 stimulation, we focused on let-7d and
      found that overexpression of let-7d down-regulated the expression of HMGA2 and in
      turn suppressed TGF-beta1-induced EMT and renal fibrogenesis. Inhibition of let
      7d increased HMGA2 expression and enhanced the profibrogenic effects of TGF-beta1
      on NRK-52E cells. Consistent with the above observations in vitro, let-7d
      expression was also decreased in the kidneys of unilateral ureter obstruction
      model, accompanied by the correspondingly increased expression of HMGA2 and
      fibrotic genes in this model. Collectively, HMGA2 and let-7d miRNA significantly
      impact on the progression of TGF-beta1-induced EMT and fibrogenesis both in vitro
      and in vivo, and they may represent novel targets for the prevention strategies
      of renal fibrosis in the context of DN.

PMID- 27693698
TI  - Identification of a new sweat gland progenitor population in mice and the role of
      their niche in tissue development.
AB  - Sweat gland cells are responsible for the regulation of body temperature and are
      critical for wound repair. Furthermore, they have the regenerative potential in
      response to injury, and show a substantial turnover during both wound healing and
      homeostasis. However, as a usual research model of sweat gland, mice have not too
      much glandular cells for experiments. In this study, we identify previously
      unreported sweat gland progenitor population in mice and characterize them. The
      progenitor characteristics of sweat gland were confirmed using cellular
      immunofluorescence assay and quantitative real-time PCR assay. K8 and K18
      expression was barely detected in the early stage of skin development (Embryo
      17.5d) and increased to a high level at P5d (postnatal 5d), then showed reduction
      at adult stage (P28d). Further investigation of K8 and K18 positive cells using
      tissue immunofluorescence revealed the presence of sweat gland progenitors in
      back epidermis of mice at early stage of sweat gland development and continuous
      reduction during the developmental process. In vivo transplantation assay with
      animal models elucidated that sweat gland specific niche in paw pads was critical
      for the development of sweat gland cells. Although the relationship between new
      sweat gland progenitors and their niche still needs to be further investigated,
      the presence of these cells implicates that there is more source ascribed to
      sweat glands in addition to serving as progenitors in mice.

PMID- 27693699
TI  - The neurocircuitry of remote cued fear memory.
AB  - Memories of threatening, fear-evoking events can persist even over a lifetime.
      While fear memory is widely considered to be a highly persistent and durable form
      of memory, its circuits are not. This article reviews the dynamic temporal
      representation of remote fear memory in the brain, at the level of local circuits
      and distributed networks. Data from the study of Pavlovian cued fear conditioning
      suggests memory retrieval remains amygdala-dependent, even over protracted time
      scales, all the while interconnected cortical and subcortical circuits are newly
      recruited and progressively reorganized. A deeper understanding into how the
      neurocircuitry of cued fear memory reorganizes with the passage of time will
      advance our ongoing search for the elusive physical changes representing fear
      memories in the brain. Considering that persistent, pathological fear memories
      are a hallmark feature of post-traumatic stress disorder (PTSD), the behavioral
      and circuit-level study of remote cued fear memory retrieval adds a key element
      towards a systems understanding of PTSD.

PMID- 27693700
TI  - Understanding heterogeneity in conduct disorder: A review of psychophysiological
      studies.
AB  - The present review is concerned with the role of different physiological systems
      (e.g., skin conductance, heart rate, electromyography, and the eye-bling startle
      reflex) in understanding heterogeneity in conduct disorder (CD). Four subtyping
      approaches are considered: age of onset, comorbid psychopathology, callous
      unemotional traits, and proactive/reactive aggression. Empirical findings are
      discussed in terms of distinct theoretical perspectives that aim to explain CD
      behaviors based on physiological over-arousal, under-arousal, and empathy
      deficits. According to the studies reviewed, the callous-unemotional (CD+CU) and
      internalizing (CD+Internalizing) sub-types can best inform CD heterogeneity.
      Findings indicated that children in the CD+CU and CD+Internalizing subtypes score
      on opposite extremes on heart rate, skin conductance and startle reactivity
      measures. Heart rate variability and respiratory sinus arrhythmia dysfunctions,
      associated with emotional dysregulation, were more evident among children in the
      CD+Internalizing group, while dysfunctional facial electromyography activity,
      which has been linked with reduced empathy, with the CD+CU group. In conclusion,
      it might be important to redefine CD diagnostic criteria based on physiological
      heterogeneity to enable the identification of distinct subtypes of CD.

PMID- 27693701
TI  - Category and design fluency in mild cognitive impairment: Performance, strategy
      use, and neural correlates.
AB  - The exploration and retrieval of words during category fluency involves different
      strategies to improve or maintain performance. Deficits in that task, which are
      common in patients with amnestic mild cognitive impairment (aMCI), mirror either
      impaired semantic memory or dysfunctional executive control mechanisms. Relating
      category fluency to tasks that place greater demands on either semantic knowledge
      or executive functions might help to determine the underlying cognitive process.
      The aims of this study were to compare performance and strategy use of 20
      patients with aMCI to 30 healthy elderly controls (HC) and to identify the
      dominant component (either executive or semantic) for better task performance in
      category fluency. Thus, the relationship between category fluency, design fluency
      and naming was examined. As fluency tasks have been associated with the superior
      frontal gyrus (SFG), the inferior frontal gyrus (IFG), and the temporal pole, we
      further explored the relationship between gray matter volume in these areas and
      both performance and strategy use. Patients with aMCI showed significantly lower
      performance and significantly less strategy use during fluency tasks compared to
      HC. However, both groups equally improved their performance when repeatedly
      confronted with the same task. In aMCI, performance during category fluency was
      significantly predicted by design fluency performance, while in HC, it was
      significantly predicted by naming performance. In HC, volume of the SFG
      significantly predicted both category and design fluency performance, and
      strategy use during design fluency. In aMCI, the SFG and the IFG predicted
      performance during both category and design fluency. The IFG significantly
      predicted strategy use during category fluency in both groups. The reduced
      category fluency performance in aMCI seems to be primarily due to dysfunctional
      executive control mechanisms rather than impaired semantic knowledge. This
      finding is directly relevant to patients in the different stages of Alzheimer's
      disease as it links the known semantic fluency deficit in this population to
      executive functions. Although patients with aMCI are impaired in both performance
      and strategy use compared to HC, they are able to increase performance over time.
      However, only HC were able to significantly improve the utilization of fluency
      strategies in both category and design fluency over time. HC seem to rely more
      heavily on the SFG during fluency tasks, while in patients with aMCI additional
      frontal brain areas are involved, possibly reflecting compensational processes.

PMID- 27693703
TI  - Nitric oxide-releasing chitosan nanoparticles alleviate the effects of salt
      stress in maize plants.
AB  - Nitric oxide (NO) is a signaling molecule involved in plant response to various
      abiotic stresses. However, the application of NO donors in agriculture is
      hampered by the instability of these compounds. Despite the successful uses of NO
      releasing nanoparticles for biomedical purposes and the variety of nanomaterials
      developed as carrier systems of agrochemicals, the potential applications of
      nanocarriers for NO delivery in plants have not yet been tested. Herein, we
      report the synthesis and characterization of chitosan nanoparticles (CS NPs)
      containing the NO donor S-nitroso-mercaptosuccinic acid (S-nitroso-MSA). The
      efficiency of these NO-releasing NPs in mitigating the deleterious effects of
      salinity on maize plants was compared to that of the non-encapsulated NO donor.
      The NPs were synthesized through ionotropic gelation process, and
      mercaptosuccinic acid (MSA), the NO donor precursor, was encapsulated into CS NPs
      (91.07% encapsulation efficiency). Free thiol groups of MSA-CS NPs were
      nitrosated, leading to S-nitroso-MSA-CS NPs (NO-releasing NPs). The incorporation
      of S-nitroso-MSA into CS NPs allowed a sustained NO release. Treatments of salt
      stressed maize plants with S-nitroso-MSA-CS NPs resulted in a higher leaf S
      nitrosothiols content compared to that of free S-nitroso-MSA. Moreover, S-nitroso
      MSA-CS NPs were more efficient than was the free NO donor in the amelioration of
      the deleterious effects of salinity in photosystem II activity, chlorophyll
      content and growth of maize plants because the protective action of the
      nanoencapsulated S-nitroso-MSA was achieved at lower dosages. Overall, these
      results demonstrate the positive impact of S-nitroso-MSA nanoencapsulation in
      increasing NO bioactivity in maize plants under salt stress.

PMID- 27693702
TI  - A single trial analysis of EEG in recognition memory: Tracking the neural
      correlates of memory strength.
AB  - Recent work in perceptual decision-making has shown that although two distinct
      neural components differentiate experimental conditions (e.g., did you see a face
      or a car), only one tracked the evidence guiding the decision process. In the
      memory literature, there is a distinction between a fronto-central evoked
      potential measured with EEG beginning at 350ms that seems to track familiarity
      and a late parietal evoked potential that peaks at 600ms that tracks
      recollection. Here, we applied single-trial regressor analysis (similar to
      multivariate pattern analysis, MVPA) and diffusion decision modeling to EEG and
      behavioral data from two recognition memory experiments to test whether these two
      components contribute to the recognition decision process. The regressor analysis
      only involved whether an item was studied or not and did not involve any use of
      the behavioral data. Only late EEG activity distinguishes studied from not
      studied items that peaks at about 600ms following each test item onset predicted
      the diffusion model drift rate derived from the behavioral choice and reaction
      times (but only for studied items). When drift rate was made a linear function of
      the trial-level regressor values, the estimate for studied items was different
      than zero. This showed that the later EEG activity indexed the trial-to-trial
      variability in drift rate for studied items. Our results provide strong evidence
      that only a single EEG component reflects evidence being used in the recegnition
      decision process.

PMID- 27693704
TI  - Astaxanthin enhances pemetrexed-induced cytotoxicity by downregulation of
      thymidylate synthase expression in human lung cancer cells.
AB  - Pemetrexed, a multitargeted antifolate agent, has demonstrated clinical activity
      in non-small cell lung cancer (NSCLC) cells. Increased expression of thymidylate
      synthase (TS) is thought to be associated with resistance to pemetrexed.
      Astaxanthin exhibits a wide range of beneficial effects including anti-cancer and
      anti-inflammatory properties. In this study, we showed that down-regulating of TS
      expression in two NSCLC cell lines, human lung adenocarcinoma H1650 and squamous
      cell carcinoma H1703 cells, with astaxanthin were associated with decreased
      MKK1/2-ERK1/2 activity. Enforced expression of constitutively active MKK1 (MKK1
      CA) vector significantly rescued the decreased TS mRNA and protein levels in
      astaxanthin-treated NSCLC cells. Combined treatment with a MKK1/2 inhibitor
      (U0126 or PD98059) further decreased the TS expression in astaxanthin-exposed
      NSCLC cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting
      ERK1/2 activity enhanced the cytotoxicity and cell growth inhibition of
      astaxanthin. Combination of pemetrexed and astaxanthin resulted in synergistic
      enhancing cytotoxicity and cell growth inhibition in NSCLC cells, accompanied
      with reduced activation of phospho-MKK1/2, phopho-ERK1/2, and TS expression.
      Overexpression of MKK1/2-CA reversed the astaxanthin and pemetrexed-induced
      synergistic cytotoxicity. Our findings suggested that the down-regulation of
      MKK1/2-ERK1/2-mediated TS expression by astaxanthin is an important regulator of
      enhancing the pemetrexed-induced cytotoxicity in NSCLC cells.

PMID- 27693705
TI  - Derivation of biomonitoring equivalent for inorganic tin for interpreting
      population-level urinary biomonitoring data.
AB  - Population-level biomonitoring of tin in urine has been conducted by the U.S.
      National Health and Nutrition Examination Survey (NHANES) and the National
      Nutrition and Health Study (ENNS - Etude nationale nutrition sante) in France.
      The general population is predominantly exposed to inorganic tin from the
      consumption of canned food and beverages. The National Institute for Public
      Health and the Environment of the Netherlands (RIVM) has established a tolerable
      daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20
      mg/kg bw per day from a 2-year feeding study in rats. Using a urinary excretion
      fraction (0.25%) from a controlled human study along with a TDI value of 0.2
      mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for urinary tin (26
      MUg/g creatinine or 20 MUg/L urine). The geometric mean and the 95th percentile
      tin urine concentrations of the general population in U.S. (0.705 and 4.5 MUg/g
      creatinine) and France (0.51 and 2.28 MUg/g creatinine) are below the BE
      associated with the TDI, indicating that the population exposure to inorganic tin
      is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the
      robustness of pharmacokinetic data forming the basis of the urinary BE
      development is medium. The availability of internal dose and kinetic data in the
      animal species forming the basis of the assessment could improve the overall
      confidence in the present assessment.

PMID- 27693706
TI  - Human umbilical cord-derived mesenchymal stem cells in acute liver injury:
      Hepatoprotective efficacy, subchronic toxicity, tumorigenicity, and
      biodistribution.
AB  - Umbilical cord-derived mesenchymal stem cells (UC-MSCs) therapy might be an
      alternative to liver transplantation for acute or chronic liver injury. The aim
      of this study was to evaluate the efficacy of human UC-MSCs on carbon
      tetrachloride (CCl4)-induced acute liver injury. In addition, its toxicity,
      tumorigenicity, and biodistribution were determined. Significant hepatoprotective
      effects of hUC-MSCs with decreased levels of hepatocellular necrosis and lobular
      neutrophilic infiltration were found. Regarding the safety of hUC-MSCs, no
      serious hUC-MSCs-related changes (body weight, food/water consumption, clinical
      symptom, urinalysis, hematology, clinical chemistry, organ weight, and
      histopathology) were observed in a 13-week subchronic toxicity study. In a 26
      week tumorigenicity study, no mice developed tumor related to hUC-MSCs
      transplantation up to 1 * 108 cells/kg. In particular, human mitochondrial
      sequence detection revealed that most hUC-MSCs were cleared from the major organs
      of the mice at 13 weeks after transplantation. There was no systemic toxicity or
      neoplastic finding either. Taken together, these results suggested that hUC-MSCs
      have great potential for future clinical treatment of acute liver disease.

PMID- 27693707
TI  - Assessment of reproductive and developmental effects of DINP, DnHP and DCHP using
      quantitative weight of evidence.
AB  - Quantitative weight of evidence (QWoE) methodology utilizes detailed scoring
      sheets to assess the quality/reliability of each publication on toxicity of a
      chemical and gives numerical scores for quality and observed toxicity. This QWoE
      methodology was applied to the reproductive toxicity data on diisononylphthalate
      (DINP), di-n-hexylphthalate (DnHP), and dicyclohexylphthalate (DCHP) to determine
      if the scientific evidence for adverse effects meets the requirements for
      classification as reproductive toxicants. The scores for DINP were compared to
      those when applying the methodology DCHP and DnHP that have harmonized
      classifications. Based on the quality/reliability scores, application of the QWoE
      shows that the three databases are of similar quality; but effect scores differ
      widely. Application of QWoE to DINP studies resulted in an overall score well
      below the benchmark required to trigger classification. For DCHP, the QWoE also
      results in low scores. The high scores from the application of the QWoE
      methodology to the toxicological data for DnHP represent clear evidence for
      adverse effects and justify a classification of DnHP as category 1B for both
      development and fertility. The conclusions on classification based on the QWoE
      are well supported using a narrative assessment of consistency and biological
      plausibility.

PMID- 27693708
TI  - Tiered application of the neutral red release and EpiOcularTM assays for
      evaluating the eye irritation potential of agrochemical formulations.
AB  - Agrochemical formulations have been underrepresented in validation efforts for
      implementing alternative eye irritation approaches but represent a significant
      opportunity to reduce animal testing. This study assesses the utility of the
      neutral red release assay (NRR) and EpiOcularTM assay (EO) for predicting the eye
      irritation potential of 64 agrochemical formulations relative to Draize data. In
      the NRR, formulations with an NRR50 value <= 50 mg/mL were categorized as UN GHS
      Cat 1 and those >250 mg/mL were classified as UN GHS Non Classified (NC). The
      accuracy, sensitivity, and specificity were 78, 85 and 76% and 73, 85 and 61% for
      identifying UN GHS 1 and NC formulations, respectively. Specificity was poor for
      formulations with NRR50 > 50 to <=250 mg/mL. The EO (ET-40 method) was explored
      to differentiate formulations that were UN GHS 1/2 and UN GHS NC. The EO resulted
      in accuracy, sensitivity, and specificity of 65%, 58% and 75% for identifying UN
      GHS NC formulations. To improve the overall performance, the assays were
      implemented using a tiered-approach where the NRR was run as a first-tier
      followed by the EO. The tiered-approach resulted in improved accuracy (75%) and
      balanced sensitivity (73%) and specificity (77%) for distinguishing between
      irritating and non-irritating agrochemical formulations.

PMID- 27693709
TI  - Can Sophorolipids prevent biofilm formation on silicone catheter tubes?
AB  - Given the impact of biofilms in health care environment and the increasing
      antibiotic resistance and/or tolerance, new strategies for preventing that
      occurrence in medical devices are obligatory. Thus, biomaterials surface
      functionalization with active compounds can be a valuable approach. In the
      present study the ability of the biosurfactants sophorolipids to prevent biofilms
      formation on silicone rubber aimed for medical catheters was investigated.
      Sophorolipids produced by Starmerella bombicola, identified by HPLC-MS/MS were
      used to cover silicone and surface characterization was evaluated through contact
      angle measurements and FTIR-ATR. Results revealed that sophorolipids presence on
      silicone surface decreased the hydrophobicity of the material and biofilm
      formation of Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922.
      Antibiofilm activity was evaluated through different methods and was more
      pronounced against S. aureus. Furthermore, biocompatibility of silicone specimens
      with HaCaT cells was also obtained. From this study it was possible to conclude
      that sophorolipids seem to be a favourable approach for coating silicone
      catheters. Such compounds may represent a novel source of antibiofilm agents for
      technological development passing through strategies of permanent
      functionalization of surfaces.

PMID- 27693710
TI  - Strategy for large-scale isolation of enantiomers in drug discovery.
AB  - A strategy for large-scale chiral resolution is illustrated by the isolation of
      pure enantiomer from a 5kg batch. Results from supercritical fluid chromatography
      will be presented and compared with normal phase liquid chromatography.
      Solubility of the compound in the supercritical mobile phase was shown to be the
      limiting factor. To circumvent this, extraction injection was used but shown not
      to be efficient for this compound. Finally, a method for chiral resolution by
      crystallization was developed and applied to give diastereomeric salt with an
      enantiomeric excess of 99% at a 91% yield. Direct access to a diverse separation
      tool box will be shown to be essential for solving separation problems in the
      most cost and time efficient way.

PMID- 27693711
TI  - Pharmacogenomics of the cytochrome P450 2C family: impacts of amino acid
      variations on drug metabolism.
AB  - Pharmacogenomics investigates DNA and RNA variations in the human genome related
      to drug responses. Cytochrome P450 (CYP) is a supergene family of drug
      metabolizing enzymes responsible for the metabolism of approximately 90% of human
      drugs. Among the major CYP isoforms, the CYP2C subfamily is of clinical
      significance because it metabolizes approximately 20% of clinically administrated
      drugs and represents several variant alleles leading to adverse drug reactions or
      altering drug efficacy. Here, we review recent progress on understanding the
      interindividual variability of the CYP2C members and the functional and clinical
      impact on drug metabolism. We summarize current advances in the molecular
      modeling of CYP2C polymorphisms and discuss the structural bases and molecular
      mechanisms of amino acid variants of CYP2C members that affect drug metabolism.

PMID- 27693712
TI  - Design of efficient computational workflows for in silico drug repurposing.
AB  - Here, we provide a comprehensive overview of the current status of in silico
      repurposing methods by establishing links between current technological trends,
      data availability and characteristics of the algorithms used in these methods.
      Using the case of the computational repurposing of fasudil as an alternative
      autophagy enhancer, we suggest a generic modular organization of a repurposing
      workflow. We also review 3D structure-based, similarity-based, inference-based
      and machine learning (ML)-based methods. We summarize the advantages and
      disadvantages of these methods to emphasize three current technical challenges.
      We finish by discussing current directions of research, including possibilities
      offered by new methods, such as deep learning.

PMID- 27693713
TI  - Molecular imaging in oncology drug development.
AB  - Tremendous breakthroughs are being made in cancer drug discovery and development.
      However, such breakthroughs come at a high financial cost. At a time when there
      is increasing pressure on drug pricing, in part because of increased life
      expectancy, it is more important than ever to drive new therapeutics towards
      patients as efficiently as possible. In this review we discuss the applications
      of molecular imaging in oncology drug development, with a focus on its ability to
      enable better early decision making, to increase efficiency and thereby to lower
      costs.

PMID- 27693714
TI  - The implications of model-informed drug discovery and development for
      tuberculosis.
AB  - Despite promising advances in the field and highly efficacious first-line
      treatment, an estimated 9.6 million people are still infected with tuberculosis
      (TB). Innovative methods are required to effectively transition the growing
      number of compounds into novel combination regimens. However, progression of
      compounds into patients occurs despite the lack of clear understanding of the
      pharmacokinetic-pharmacodynamic (PKPD) relationships. The PreDiCT-TB consortium
      was established in response to the existing gaps in TB drug development. The aim
      of the consortium is to develop new preclinical tools in concert with an in
      silico model-based approach, grounded in PKPD principles. Here, we highlight the
      potential impact of such an integrated framework on the various stages of TB drug
      development and on the dose rationale for drug combinations.

PMID- 27693716
TI  - Downregulation of melanogenesis: drug discovery and therapeutic options.
AB  - Melanin, primarily responsible in humans for hair, eye and skin pigmentation, is
      produced by melanocytes through a process called melanogenesis. However, the
      abnormal accumulation of melanin causes dermatological problems such as cafe-au
      lait macules ephelides (freckles), solar lentigo (age spots) and melasma, as well
      as cancer and vitiligo. Hence the regulation of melanogenesis is very important
      for treating hyperpigmentary disorders. Numerous antimelanogenic agents that
      target tyrosinase activity and/or stability, melanosome maturation, transfer and
      trafficking, or melanogenesis-related signaling pathways have been developed.
      This article reviews recent advances in research and development of human
      tyrosinase and melanogenesis-related signaling pathway inhibitors. Attempts have
      been made to provide a complete description of the mechanism of action of
      inhibitors on various melanogenesis signaling pathways.

PMID- 27693717
TI  - Understanding osteomyelitis and its treatment through local drug delivery system.
AB  - Chronic osteomyelitis is a major challenge in bone surgery. Conventional use of
      antibiotics is not an effective way to control the malaise due to so many
      reasons. Determination of optimal treatment strategy becomes difficult for the
      orthopaedic surgeons and as a consequence, the patients suffer not only from
      therapeutic failure but also due to adverse side effects of antibiotics and
      financial loss due to additional stay at hospitals. A wide application of carrier
      systems, as a medium for local delivery of antibiotics, is being used
      experimentally and clinically for the treatment of osteomyelitis. This kind of
      delivery system provides sustained higher concentration of antibiotics at the
      infection site with reduced possibility of toxicity. This review highlight
      etiology and pathophysiology of osteomyelitis, current therapeutic options with
      their limitations, and potentiality of biomaterial based carrier materials
      impregnated with antibiotics as local delivery approach.

PMID- 27693715
TI  - Cyclooxygenase-2 in glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) represents the most prevalent brain primary tumor,
      yet there is a lack of effective treatment. With current therapies, fewer than 5%
      of patients with GBM survive more than 5 years after diagnosis. Mounting evidence
      from epidemiological studies reveals that the regular use of nonsteroidal anti
      inflammatory drugs (NSAIDs) is correlated with reduced incidence of GBM,
      suggesting that cyclooxygenase-2 (COX-2) and its major product within the brain,
      prostaglandin E2 (PGE2), are involved in the development and progression of GBM.
      Here, we highlight our current understanding of COX-2 in GBM proliferation,
      apoptosis, invasion, angiogenesis, and immunosuppression by focusing on recent in
      vitro and in vivo experimental data. We also discuss the feasibility of COX-2 as
      a therapeutic target for GBM in light of the latest human studies.

PMID- 27693718
TI  - Synthesis and characterization of chitosan-TiO2:Cu nanocomposite and their
      enhanced antimicrobial activity with visible light.
AB  - In the present investigation, novel strategy for the preparation of hybrid
      nanocomposite containing organic polymer (Chitosan) and inorganic (TiO2:Cu)
      nanoparticles (NPs) has been developed and demonstrated its biomedical
      application. The sol-gel and ultra-sonication method assisted for the preparation
      of uniformly distributed Chitosan-TiO2:Cu (CS-CT) nanocomposite. The structural
      properties of prepared CS-CT nanocomposite were studied by XRD and FTIR
      techniques. The XPS was used to estimate elemental composition of the
      nanocomposite. Thermal properties were studied using TGA. TEM and SEM analysis
      showed the non-spherical nature of NPs with the average mean diameter 16nm. The
      optical properties were analyzed with UV-vis diffuse reflectance spectroscopy to
      confirm optical absorption in the visible region of light. Where CS-CT showed
      200% enhanced light mediated photocatalytic antimicrobial activity against
      microorganism (Escherichia coli and Staphylococcus aureus) as compared with
      control. The antimicrobial activity of CS-CT nanocomposite in presence of light
      is found to be enhanced than that of its components, this is due to synergistic
      effect of organic and inorganic material complimenting each other's activity. The
      OH radicals release studied by PL spectroscopy on the surface of nanocomposite
      was used to examine antibacterial activity. Cytotoxicity assessment of CS-CT on
      human fibroblast cells was performed by MTT assay.

PMID- 27693719
TI  - Attomolar electrochemical detection of the BCR/ABL fusion gene based on an
      amplifying self-signal metal nanoparticle-conducting polymer hybrid composite.
AB  - In the last ten years, conjugated polymers started to be used in the
      immobilization of nucleic acids via non-covalent interactions. In the present
      study, we describe the construction and use of an electrochemical DNA biosensor
      based on a nanostructured polyaniline-gold composite, specifically developed for
      the detection of the BCR/ABL chimeric oncogene. This chromosome translocation is
      used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous
      leukemia (CML) and acute lymphocytic leukemia (ALL). The working principle of the
      biosensor rests on measuring the conductivity resulting from the non-covalent
      interactions between the hybrid nanocomposite and the DNA probe. The
      nanostructured platform exhibits a large surface area that enhances the
      conductivity. Positive cases, which result from the hybridization between DNA
      probe and targeted gene, induce changes in the amperometric current and in the
      charge transfer resistance (RCT) responses. Atomic force microscopy (AFM) images
      showed changes in the genosensor surface after exposure to cDNA sample of patient
      with leukemia, evidencing the hybridization process. This new hybrid sensing
      platform displayed high specificity and selectivity, and its detection limit is
      estimated to be as low as 69.4 aM. The biosensor showed excellent analytical
      performance for the detection of the BCR/ABL oncogene in clinical samples of
      patients with leukemia. Hence, this electrochemical sensor appears as a simple
      and attractive tool for the molecular diagnosis of the BCR/ABL oncogene even in
      early-stage cases of leukemia and for the monitoring of minimum levels of
      residual disease.

PMID- 27693720
TI  - Self-oriented monolayer immobilization of ovalbumin and B. cereus antibody
      molecules on a chemically modified surface of silicon nitride fosters the
      enhancement of capture of bio-agents.
AB  - A fast and reliable detection of biological agents in air is of a crucial
      importance to respond to terrorist attacks. With the aim to efficiently react to
      such hazards there is the need to develop highly sensitive and specific detection
      analytical devices for selective and quantitative detection of biological threats
      such as the presence of Bacillus anthracis spores and/or the presence of Ricin A
      toxins. In this study we explored how to achieve an oriented immobilization of
      antibody molecules on silicon nitride surfaces to improve their efficiency to
      bind to specific target molecules. In particular, we used two different methods
      to covalently immobilize antibody molecules on silicon nitride surfaces, and here
      we report the obtained results.

PMID- 27693721
TI  - Nucleobases Undergo Dynamic Rearrangements during RNA Tertiary Folding.
AB  - The tertiary structure of the GTPase center (GAC) of 23S ribosomal RNA (rRNA) as
      seen in cocrystals is extremely compact. It is stabilized by long-range hydrogen
      bonds and nucleobase stacking and by a triloop that forms within its three-way
      junction. Its folding pathway from secondary structure to tertiary structure has
      not been previously observed, but it was shown to require Mg2+ ions in
      equilibrium experiments. The fluorescent nucleotide 2-aminopurine was substituted
      at selected sites within the 60-nt GAC. Fluorescence intensity changes upon
      addition of MgCl2 were monitored over a time-course from 1ms to 100s as the RNA
      folds. The folding pathway is revealed here to be hierarchical through several
      intermediates. Observation of the nucleobases during folding provides a new
      perspective on the process and the pathway, revealing the dynamics of nucleobase
      conformational exchange during the folding transitions.

PMID- 27693722
TI  - Abnormal findings in brainstem auditory evoked response at 36-37weeks of
      postconceptional age in babies with neonatal chronic lung disease.
AB  - AIM: To examine brainstem auditory function at 36-37weeks of postconceptional age
      in preterm infants who are diagnosed to have neonatal chronic lung disease (CLD).
      STUDY DESIGN: Preterm infants, born at 31 and less weeks of gestation, were
      studied at 36-37weeks of postconceptional age when they were diagnosed to have
      neonatal CLD. Brainstem auditory evoked response (BAER) was recorded and analyzed
      at different click rates. RESULTS: Compared with healthy controls at the same
      postconceptional age, the CLD infants showed a slightly increase in BAER wave V
      latency. However, the I-V, and III-V interpeak intervals in the CLD infants were
      significantly increased. The III-V/I-III interval ratio was also significantly
      increased. The amplitudes of BAER waves III and V in the CLD infants tended to be
      reduced. These BAER findings were similar at all 21, 51 and 91/s clicks, although
      the abnormalities tended to be more significant at higher than at low click
      rates. CONCLUSION: At 36-37weeks of postconceptional age, BAER was abnormal in
      preterm infants who were diagnosed to have neonatal CLD. This suggests that at
      time when the diagnosis of CLD is made there is functional impairment, reflecting
      poor myelination, in the brainstem auditory pathway in preterm infants with
      neonatal CLD.

PMID- 27693723
TI  - Early determinants of vagal activity at preschool age - With potential dependence
      on sex.
AB  - BACKGROUND: In children, autonomic nervous function is related to various highly
      prevalent health problems and might therefore represent an early indicator of ill
      health. AIMS: We aimed to investigate the role of early-life exposures and
      physical activity (PA) as potential determinants of autonomic function at
      preschool age. STUDY DESIGN AND SUBJECTS: We used an existing longitudinal data
      set of repeated vagal tone measurements (assessed via heart rate recovery (HRR))
      and retrospectively assessed early-life exposures in 1052 children (mean age:
      59.4months, 47.5% girls) from 52 preschools in Germany recruited from 2008 to
      2010. OUTCOME MEASURES: HRR 1min after submaximal exercise served as primary
      outcome. Through multilevel linear regression analysis adjusted for demographic
      and socioeconomic factors, we assessed the association between repeatedly
      measured HRR and pregnancy smoking status, breastfeeding and objectively measured
      PA. RESULTS: Besides significant regression coefficients for previously described
      correlates of HRR (sex, age), we could show positive associations of HRR with
      breastfeeding (six versus zero months: +4.2 beats per minute (BPM), p=0.004) and
      PA (+1.0BPM for 10min increase of moderate-to-vigorous PA/day, p<0.001). Smoking
      before and during pregnancy showed no significant association with HRR in the
      total sample. However, we found interactions between sex and smoking before and
      during pregnancy as well as between sex and breastfeeding, suggesting significant
      associations with HRR only in girls. CONCLUSIONS: Besides PA, early pre- and
      postnatal exposures seem to have long-lasting effects on children's autonomic
      function, still recordable at preschool age. Our data suggest that these effects
      might be sex-dependent.

PMID- 27693724
TI  - Significance of optineurin mutations in glaucoma and other diseases.
AB  - Glaucoma is one of the leading causes of bilateral blindness, affecting nearly 57
      million people worldwide. Glaucoma is characterized by a progressive loss of
      retinal ganglion cells and is often associated with intraocular pressure (IOP).
      Normal tension glaucoma (NTG), marked by normal IOP but progressive glaucoma, is
      incompletely understood. In 2002, Sarfarazi et al. identified FIP-2 gene
      mutations responsible for hereditary NTG, renaming this gene "optineurin" (OPTN).
      Further investigations by multiple groups worldwide showed that OPTN is involved
      in several critical cellular functions, such as NF-kappaB regulation, autophagy,
      and vesicle transport. Recently, OPTN mutations were found to cause amyotrophic
      lateral sclerosis (ALS). Surprisingly, a mutation in the OPTN interacting
      protein, i.e., the duplication of TANK binding protein 1 (TBK1) gene, also can
      cause both NTG and ALS. These phenotypically distinct neuronal diseases are now
      merging into one common pathological mechanism by these two genes. TBK1
      inhibition has emerged as a potential therapy for NTG. In this manuscript, we
      focus on the OPTN E50K mutation, the most common mutation for NTG, to describe
      the molecular mechanism of NTG by expressing a mutant Optn gene in cells and
      genetically modified mice. Patient iPS cells were developed and differentiated
      into neural cells to observe abnormal behavior and the impact of the E50K
      mutation. These in vitro studies were further extended to identify the inhibitors
      BX795 and amlexanox, which have the potential to reverse the disease-causing
      phenomenon in patient's neural cells. Here we show for the first time that
      amlexanox protects RGCs in Optn E50K knock-in mice.

PMID- 27693726
TI  - Utilising light-emitting diodes of specific narrow wavelengths for the
      optimization and co-production of multiple high-value compounds in Porphyridium
      purpureum.
AB  - The effect of specific narrow light-emitting diode (LED) wavelengths (red, green,
      blue) and a combination of LED wavelengths (red, green and blue - RGB) on biomass
      composition produced by Porphyridium purpureum is studied. Phycobiliprotein,
      fatty acids, exopolysaccharides, pigment content, and the main macromolecules
      composition were analysed to determine the effect of wavelength on multiple
      compounds of commercial interest. The results demonstrate that green light plays
      a significant role in the growth of rhodophyta, due to phycobiliproteins being
      able to harvest green wavelengths where chlorophyll pigments absorb poorly.
      However, under multi-chromatic LED wavelengths, P. purpureum biomass accumulated
      the highest yield of valuable products such as eicosapentaenoic acid (~2.9% DW),
      zeaxanthin (~586MUgg-1DW), beta-carotene (397MUgg-1DW), exopolysaccharides
      (2.05g/L-1), and phycobiliproteins (~4.8% DW). This increased accumulation is
      likely to be the combination of both photo-adaption and photo-protection, under
      the combined specific wavelengths employed.

PMID- 27693725
TI  - The impact of furfural concentrations and substrate-to-biomass ratios on
      biological hydrogen production from synthetic lignocellulosic hydrolysate using
      mesophilic anaerobic digester sludge.
AB  - This study evaluated the impact of furfural (a furan derivative) on hydrogen
      production rates and yields at initial substrate-to-microorganism ratios (S
      degrees /X degrees ) of 4, 2, 1, and 0.5gCOD/gVSS and furfural concentrations of
      4, 2, 1, and 0.5g/L. Fermentation studies were carried out in batches using
      synthetic lignocellulosic hydrolysate as substrate and mesophilic anaerobic
      digester sludge as seed. Contrary to other literature studies where furfural was
      inhibitory, this study showed that furfural concentrations of up to 1g/L enhanced
      hydrogen production with yields as high as 19% from the control (batch without
      furfural). Plots of hydrogen yields against gfurfural/gsugars and hydrogen yields
      versus gfurfural/gbiomass showed negative linear correlation indicating that
      these parameters influence biohydrogen production. Regression analysis indicated
      that gfurfural/gsugarsinitial exerted a greater effect on the degree of
      inhibition of hydrogen production than gfurfural/gVSSfinal.

PMID- 27693727
TI  - Simultaneous hydrolysis and co-fermentation of whey lactose with wheat for
      ethanol production.
AB  - Whey permeate was used as a co-substrate to replace part of the wheat for ethanol
      production by Saccharomyces cerevisiae. The simultaneous saccharification and
      fermentation was achieved with beta-galactosidase added at the onset of the
      fermentation to promote whey lactose hydrolysis. Aspergillus oryzae and
      Kluyveromyces lactis beta-galactosidases were two enzymes selected and used in
      the co-fermentation of wheat and whey permeate for the comparison of their
      effectiveness on lactose hydrolysis. The possibility of co-fermentations in both
      STARGEN and jet cooking systems was investigated in 5L bioreactors. Ethanol
      yields from the co-fermentations of wheat and whey permeate were evaluated. It
      was found that A. oryzae beta-galactosidase was more efficient for lactose
      hydrolysis during the co-fermentation and that whey permeate supplementation can
      contribute to ethanol yield in co-fermentations with wheat.

PMID- 27693728
TI  - Simulation of biomass-steam gasification in fluidized bed reactors: Model setup,
      comparisons and preliminary predictions.
AB  - A user-defined solver integrating the solid-gas surface reactions and the multi
      phase particle-in-cell (MP-PIC) approach is built based on the OpenFOAM software.
      The solver is tested against experiments. Then, biomass-steam gasification in a
      dual fluidized bed (DFB) gasifier is preliminarily predicted. It is found that
      the predictions agree well with the experimental results. The bed material
      circulation loop in the DFB can form automatically and the bed height is about
      1m. The voidage gradually increases along the height of the bed zone in the
      bubbling fluidized bed (BFB) of the DFB. The U-bend and cyclone can separate the
      syngas in the BFB and the flue gas in the circulating fluidized bed. The
      concentration of the gasification products is relatively higher in the conical
      transition section, and the dry and nitrogen-free syngas at the BFB outlet is
      predicted to be composed of 55% H2, 20% CO, 20% CO2 and 5% CH4.

PMID- 27693729
TI  - Comparison of two-stage acid-alkali and alkali-acid pretreatments on enzymatic
      saccharification ability of the sweet sorghum fiber and their physicochemical
      characterizations.
AB  - Two-stage acid/alkali pretreatment was used to enhance the saccharification
      efficiency of sweet sorghum fiber. The physicochemical characterizations of the
      pretreated fibers were evaluated by SEM, FTIR and XRD. The acid and alkali
      sequence in the two-stage pretreatment process was compared, and their dosage was
      optimized. The results indicated that the two-stage pretreatment showed better
      saccharification performance when compared with conventional single stage
      pretreatment. And compared with the acid-alkali sequence, the alkali-acid
      sequence achieved higher glucose yield (0.23g.g-1) under the optimized
      conditions, which was 1.64 and 1.21 times higher than that of the single stage
      and the acid-alkali pretreatments, respectively. Overall, the two-stage
      pretreatment process is a promising approach to achieve high fermentable glucose
      conversion rate of cellulosic material.

PMID- 27693730
TI  - Menopause and Parkinson's disease. Interaction between estrogens and brain renin
      angiotensin system in dopaminergic degeneration.
AB  - The neuroprotective effects of menopausal hormonal therapy in Parkinson's disease
      (PD) have not yet been clarified, and it is controversial whether there is a
      critical period for neuroprotection. Studies in animal models and clinical and
      epidemiological studies indicate that estrogens induce dopaminergic
      neuroprotection. Recent studies suggest that inhibition of the brain renin
      angiotensin system (RAS) mediates the effects of estrogens in PD models. In the
      substantia nigra, ovariectomy induces a decrease in levels of estrogen receptor
      alpha (ER-alpha) and increases angiotensin activity, NADPH-oxidase activity and
      expression of neuroinflammatory markers, which are regulated by estrogen
      replacement therapy. There is a critical period for the neuroprotective effect of
      estrogen replacement therapy, and local ER-alpha and RAS play a major role.
      Astrocytes play a major role in ER-alpha-induced regulation of local RAS, but
      neurons and microglia are also involved. Interestingly, treatment with
      angiotensin receptor antagonists after the critical period induced
      neuroprotection.

PMID- 27693731
TI  - The influence of subgroup diagnosis on radiographic and clinical outcomes after
      lumbar fusion for degenerative disc disorders revisited: a systematic review of
      the literature.
AB  - BACKGROUND CONTEXT: Understanding the influence of preoperative diagnosis on
      outcomes for lumbar fusion surgery improves the quality of research and outcomes
      data, and helps guide treatment decisions. PURPOSE: We sought to perform a
      systematic review of the literature published between 2000 and 2014 regarding
      lumbar fusion outcomes for degenerative disorders. An assessment of the influence
      of subgroup diagnosis on outcomes as well as the quality of this body of
      literature was performed. STUDY DESIGN: Systematic review PATIENT SAMPLE: The 100
      studies ultimately included involved adult patients (n=8,706) undergoing fusion
      surgery for degenerative disorders of the lumbar spine. OUTCOME MEASURES: Visual
      analog scale (VAS) pain scores, complication rates, and determination of
      successful fusion METHODS: With adherence to the PRISMA guidelines, electronic
      searches were performed through PubMed, Scopus, and Web of Science to identify
      all studies involving lumbar fusion for degenerative disc disorders from January
      2000 to August 2014. Studies were eligible for inclusion if they addressed adult
      patients treated with lumbar fusion for one of the following: stable degenerative
      disc disease, unstable degenerative disc disease, degenerative disc disease not
      specified (DDDns), herniated disc (DH), degenerative spondylolisthesis (DDDsp),
      and adult degenerative scoliosis (DDDsc). Abstracted data included the number of
      patients, preoperative diagnosis, fusion technique, complications, fusion rate,
      and clinical outcomes. RESULTS: One hundred articles met inclusion criteria and
      yielded data for 8,706 patients. Forty-three studies included data for clinical
      improvement (VAS scores). The mean clinical improvement in VAS scores was
      significantly different among the diagnoses (p<.001), with DDDsp demonstrating
      the highest improvement (60%) and DDDns having the lowest (45%). Eighty-five
      studies included data for complication rates. Complication rates differed
      significantly (p<.001), with the highest rate seen in the DDDsc group (18%),
      followed by DDDsp (14%). Seventy-eight studies included data for fusion. The
      pooled odds of fusion for prospective studies were 6.93 (95% CI 4.75, 10.13).
      There was no evidence of publication bias. CONCLUSIONS: A relationship between
      outcomes and subgroup diagnosis was demonstrated. This review demonstrated a
      higher quality of evidence in the literature, and greater overall fusion rates
      compared to similar studies published in the 1980s and 1990s.

PMID- 27693732
TI  - Oswestry Disability Index: a psychometric analysis with 1,610 patients.
AB  - BACKGROUND: One-fourth of the adult US population has or will experience back
      pain and has undergone one of a myriad of treatments. Understanding the outcomes
      of these many treatments from pharmacologic to surgical, from manipulation to
      modality, allows for a better understanding and value-driven decision making.
      Patient-reported outcome measures are the current standard and include general
      and disease-specific measures. The Oswestry Disability Index (ODI) is the most
      commonly used disease-specific patient-reported outcome tool to measure
      functional disability related to back pain. Few studies have evaluated its
      psychometric properties in a large patient sample using a modern tool such as the
      Rasch analysis model. This study aims to identify the benefits and deficiencies
      of the ODI as an outcome tool for assessing patients with back pain. PURPOSE:
      This study aimed to investigate the psychometric properties, performance, and
      applicability of the ODI in patients with back pain who visited a university
      based outpatient clinic. STUDY DESIGN: This study used a secondary analysis
      assessment of diagnostic tool on consecutive patients. PATIENT SAMPLE: The sample
      comprised 1,610 patients visiting an academic spine center. OUTCOME MEASURES: The
      ODI was the outcome measure. METHODS: Detailed Rasch analysis of the ODI was
      performed. Standard descriptive statistics were also assessed. RESULTS: The ODI
      performed well overall. It demonstrated suboptimal unidimensionality (ie,
      unexplained variance after accounting for the first dimension) of 8.3%. Person
      reliability was good, at 0.85, and item reliability was excellent, at 1.00. The
      overall item fit for the ODI was good with an outfit mean square of 1.02. The ODI
      had a floor effect of 29.9% and ceiling effect of 3.9%. The raw score to measure
      correlation of the ODI was excellent, at 0.944. CONCLUSIONS: The ODI performed
      relatively well overall, with some problematic findings. It had good person and
      item reliability, although it did not demonstrate strong evidence of
      unidimensionality. The ODI has moderately poor coverage, with a very large floor
      effect and small ceiling effect, which could present a challenge in interpreting
      results of scores at the end of the spectrum.

PMID- 27693733
TI  - Pyridoxal oxime derivative potency to reactivate cholinesterases inhibited by
      organophosphorus compounds.
AB  - Organophosphorus (OP) nerve agents (sarin, tabun VX and soman) inhibit the enzyme
      acetylcholinesterase (AChE, EC 3.1.1.7) by binding to its active site while
      preventing neurotransmission in the cholinergic synapses. The protection and
      treatment of this kind of poisoning are still a challenge as we are yet to
      discover an antidote that would be effective in all cases of poisoning. To aid
      the search for more efficient antidotes, we evaluated the ability of nine
      pyridoxal oxime derivatives, prepared by a novel synthetic pathway, to reactivate
      recombinant human AChE and the related purified human plasma
      butyrylcholinesterase (BChE, EC 3.1.1.8) inhibited by VX, tabun and paraoxon.
      Oximes are derivatives of vitamin B6 bearing a phenacyl moiety attached to the
      quaternary nitrogen atom and having various substituents on the phenyl ring. As
      the results have shown, the tested oximes were in general more efficient in the
      reactivation of OP-inhibited BChE than AChE. The highest observed rate was in the
      case of VX-inhibited BChE reactivation, where kobs was 0.0087min-1 and the
      reactivation maximum of 90% was achieved within 5h. The cholinesterases displayed
      a binding affinity for these derivatives in a MUmolar range no matter the
      substituent on their rings which was in accordance with the molecular modelling
      results showing a similar binding pattern for all oximes within the active site
      of both AChE and BChE. Such a positioning reveals also that hydroxy and a metoxy
      substituents at the vicinity of the oxime moiety present a possible steric
      hindrance explaining the reactivation results.

PMID- 27693734
TI  - Targeted delivery of rifampicin to tuberculosis-infected macrophages: design, in
      vitro, and in-vivo performance of rifampicin-loaded poly(ester amide)s
      nanocarriers.
AB  - We have developed a nano drug delivery system for the treatment of tuberculosis
      (TB) using rifampicin (RF) encapsulated in poly(ester amide)s nanoparticles (PEA
      RF-NPs), which are biocompatible polymers. In this study, biodegradable amino
      acid based poly(ester amide)s (PEAs) were synthesized by the poly condensation
      reaction and RF-loaded NPs were fabricated by the dialysis method. The surface
      morphology and in-vitro drug release efficiency were examined. The effect of time
      and temperature on the cellular uptake of PEA-RF-NPs in NR8383 cells was
      evaluated. Fluorescence microscopic results of PEA-RF-NPs from NR8383 cell lines
      suggest its potential application in treating TB. The antibacterial activity of
      RF against Mycobacterium smegmatis was also evaluated. Based on these results,
      this approach provides a new means for controlled and efficient release of RF
      using the PEA-NPs delivery system and is promising for the treatment of TB.

PMID- 27693735
TI  - A novel chitosan-polyethylene oxide nanofibrous mat designed for controlled co
      release of hydrocortisone and imipenem/cilastatin drugs.
AB  - Antimicrobial chitosan-polyethylene oxide (CS-PEO) nanofibrous mats containing
      ZnO nanoparticles (NPs) and hydrocortisone-imipenem/cilastatin-loaded ZnO NPs
      were produced by electrospinning technique. The FE-SEM images displayed that the
      spherical ZnO NPs were ~70-200nm in size and the CS-PEO nanofibers were very
      uniform and free of any beads which had average diameters within the range of ~20
      130nm. For all of the nanofibrous mats, the water uptakes were the highest in
      acidic medium but they were decreased in the buffer and the least swellings were
      obtained in the alkaline environment. The drug incorporated mat preserved its
      bactericidal activity even after it was utilized in the release experiment for
      8days in the PBS buffer. The hydrocortisone release was increased to 82% within
      first 12h while the release rate of imipenem/cilastatin was very much slower so
      that 20% of the drug was released during this period of time suggesting this
      nanofibrous mat is very suitable to inhibit inflammation (by hydrocortisone) and
      infection (using imipenem/cilastatin antibiotic and ZnO NPs) principally for the
      wound dressing purposes.

PMID- 27693736
TI  - Production of nabumetone nanoparticles: Effect of molecular weight, concentration
      and nature of cellulose ether stabiliser.
AB  - The ability of a range of hydrophilic nonionic cellulose ethers (CEs) (namely
      methylhydroxethylcellulose, hydroxypropylmethylcellulose,
      ethylhydroxyethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose) to
      prepare stable nabumetone nanoparticles (<1000nm, as measured by laser
      diffraction) using wet-bead milling has been investigated. Due to the limited
      range of CE molecular weights commercially available, the CEs were degraded using
      ultrasonication for varying lengths of time to yield CEs of lower molecular
      weight. Of the CEs tested, only hydroxyethylcellulose was found not to stabilise
      the production of nabumetone nanoparticles at any of the molecular weights
      tested, namely viscosity average molecular weights (Mv) in the range of 236
      33kg/mol. All other CEs successfully stabilised nabumetone nanoparticles, with
      the lower molecular weight/viscosity polymers within a series being more likely
      to result in nanoparticle production than their higher molecular weight
      counterparts. Unfortunately due to the nature of the ultrasonication process, it
      was not possible to compare the size of nabumetone particles produced using
      polymers of identical Mv. There was, however, enough similarity in the Mv of the
      various polymers to draw the general conclusion that there was no strong
      correlation between the Mv of the various polymers and their ability to produce
      nanoparticles. For example hydroxypropylcellulose of 112.2kg/mol or less
      successfully produced nanoparticles while only ethylhydroxyethylcellulose and
      hydroxypropylmethyl polymers of 52 and 38.8kg/mol or less produced nanoparticles.
      These results suggest that polymer molecular weight is not the only determinant
      of nanoparticle production and that structure of the polymer is at least as
      important as its molecular weight. In particular the hydrophobic nature of the CE
      was thought to be an important factor in the production of nabumetone
      nanoparticles: the more hydrophobic the polymer, the stronger its interaction
      with nabumetone and the greater its ability to produce nanoparticles. In this
      context HPC was the most hydrophobic polymer and HEC the least hydrophobic.

PMID- 27693737
TI  - Gold nanoparticles enhance 5-fluorouracil anticancer efficacy against colorectal
      cancer cells.
AB  - 5-Fluorouracil (5-FU), an antimetabolite drug, is extensively used in the
      treatment solid tumors. However, its severe side effects limit its clinical
      benefits. To enhance 5-FU anticancer efficacy and reduce its side effects it was
      loaded onto gold nanoparticles (GNPs) using two thiol containing ligands,
      thioglycolic acid (TGA) and glutathione (GSH). The GNPs were prepared at
      different 5-FU/ligand molar ratios and evaluated using different techniques.
      Anticancer efficacy of 5-FU/GSH-GNPs was studied using flow cytometry in
      cancerous tissue obtained from patients having colorectal cancer. The GNPs were
      spherical in shape and had a size of ~9-17nm. Stability of the GNPs and drug
      release were studied as a function of salt concentration and solution pH. Maximum
      5-FU loading was achieved at 5-FU/ligand molar ratio of 1:1 and 2:1 for TGA-GNPs
      and GSH-GNPs, respectively. GNPs coating with pluronic F127 improved their
      stability against salinity. 5-FU release from GNPs was slow and pH-dependent. 5
      FU/GSH-GNPs induced apoptosis and stopped the cell cycle progression in
      colorectal cancer cells. They also had a 2-fold higher anticancer effect compared
      with free 5-FU. These results confirm the potential of GNPs to enhance 5-FU
      anticancer efficacy.

PMID- 27693738
TI  - Labelling, molecular modelling and biological evaluation of vardenafil: a
      potential agent for diagnostic evaluation of erectile dysfunction.
AB  - 99mTc-tricarbonyl-vardenafil was specifically radiosynthesized for diagnostic
      evaluation of erectile dysfunction with a radiochemical yield ~97.2%. It was
      stable in saline up to 15h and in serum for more than 6h. The radiocomplex was
      lipophilic with a partition coefficient ~1.32 and plasma protein binding 72-76%.
      Its structure was determined using molecular mechanics and confirmed by NMR. In
      silico docking to its target PDE5 enzyme was performed. The radiocomplex
      inhibitory activity was assessed and its IC50 was 0.7nM. Biodistribution in
      normal rats and biological evaluation in rat models of erectile dysfunction were
      performed. The results strongly suggested that 99mTc-tricarbonyl-vardenafil is a
      good candidate to image erectile dysfunction in humans.

PMID- 27693739
TI  - Two new steroidal glycosides with unique structural feature of 14alpha-hydroxy
      5beta-steroids from Reineckia carnea.
AB  - Two new steroidal glycosides (1-2) were isolated from the roots of Reineckia
      carnea, together with three known compounds (3-5). Their structures were
      determined on the basis of chemical methods and spectral data. Compounds 1-2 were
      the unique steroidal glycosides possessing structural feature of 14alpha-hydroxy
      5beta-steroids, and compounds 4-5 were isolated from R. carnea for the first
      time. The isolated compounds (1-5) were tested in vitro for their cytotoxic
      activities against the A549, HepG 2 and Caski cancer cell lines. Among them, the
      compounds 2 and 3 showed cytotoxicity against Caski cancer cell line with IC50
      values of 34.4 and 3.7MUM, respectively.

PMID- 27693740
TI  - Protective effects of cycloartane triterpenoides from Passiflora edulis Sims
      against glutamate-induced neurotoxicity in PC12 cell.
AB  - Four new cycloartane triterpenoids, 1alpha,3beta-dihydroxy-16-keto-24(31)-en
      cycloartane (1), 31-methoxyl-passifloic acid (2), cyclopassifloside XIV (3), and
      cyclopassifloside XV (4), together with six known compounds (5-10) were isolated
      from Passiflora edulis Sims. Their structures were elucidated on the basis of
      extensive spectroscopic analysis. All the compounds were evaluated for protective
      effects against damage of PC12 cell induced by glutamate according to traditional
      usage of the herbal medicine, and the results indicated that cycloartane
      triterpenoids maybe one of the active compositions of P. edulis Sims for the
      treatment of neurodegenerative disease.

PMID- 27693741
TI  - Apigenin protects mice from pneumococcal pneumonia by inhibiting the cytolytic
      activity of pneumolysin.
AB  - Streptococcus pneumoniae is an important human pathogenic bacterium that can
      cause various life-threatening infections. Pneumolysin (PLY), the pore-forming
      toxin that forms large pores in the cell membrane, is a key virulence factor
      secreted by S. pneumoniae that penetrates the physical defenses of the host and
      plays an important role in the pathogenesis of pneumococcal diseases, such as
      pneumonia, meningitis, bacteremia and otitis media. This study showed that
      apigenin, one of the bioflavonoids widely found in herbs, inhibits PLY-induced
      hemolysis by inhibiting the oligomerization of PLY and has no anti-S. pneumoniae
      activity. In addition, when PLY was incubated with human alveolar epithelial
      (A549) cells, apigenin could effectively alleviate PLY-mediated cell injury. In
      vivo studies further demonstrated that apigenin could protect mice against S.
      pneumoniae pneumonia. These results imply that apigenin could directly interact
      with PLY to decrease the pathogenicity of S. pneumoniae and that novel
      therapeutics against S. pneumoniae PLY might provide greater effectiveness in
      combatting S. pneumoniae pneumonia.

PMID- 27693742
TI  - A new steroidal saponin, furotrilliumoside from Trillium tschonoskii inhibits
      lipopolysaccharide-induced inflammation in Raw264.7 cells by targeting PI3K/Akt,
      MARK and Nrf2/HO-1 pathways.
AB  - A new steroidal saponin, furotrilliumoside (FT) was isolated from the roots and
      rhizomes of Trillium tschonoskii Maxim. Its structure was elucidated on the basis
      of 1D- and 2D-NMR spectroscopic data as well as HR-ESI-MS analysis. FT showed
      superior activity of inhibiting NO production of RAW264.7 cells induced by
      lipopolysaccharide (LPS) in the preliminary biological screening. In order to
      develop novel therapeutic drug for acute and chronic inflammatory disorders, the
      anti-inflammatory activity and underlying mechanism of FT were investigated in
      LPS-induced RAW264.7 cells. The results showed that FT could reduce LPS-induced
      expression of inducible nitric oxide synthase (iNOS) and then resulted in the
      decrement of NO production. More meaningful, FT could down-regulate the
      expression of cyclooxygenase-2 (COX-2) and decrease the expressions of pro
      inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6
      (IL-6) and interleukin-1beta (IL-1beta), in both gene and protein levels. In
      mechanism study, FT blocked the LPS-induced upregulation of phosphorylated
      phosphoinositide-3-kinase and Akt (PI3K/Akt). Furthermore, FT inhibited the
      translocation of nuclear factor-kappa B (NF-kappaB) through the prevention of
      inhibitory factor kappa B alpha (IkappaBalpha) phosphorylation and degradation
      and also suppressed the mitogen-activated protein kinases (MAPK) signaling
      pathway in LPS-stimulated RAW264.7 macrophages. In addition, FT upregulated heme
      oxygenase-1 (HO-1) expression via nuclear translocation of nuclear factor E2
      related factor 2 (Nrf2). Taken together, FT might act as a natural agent to treat
      some inflammatory diseases by targeting PI3K/Akt, MARK and Nrf2/HO-1 pathways.

PMID- 27693743
TI  - Polyphenolic compounds with antioxidant potential and neuro-protective effect
      from Cimicifuga dahurica (Turcz.) Maxim.
AB  - Three new phenolic compounds (1-3), along with five known compounds (4-8) were
      isolated from the rhizome of Cimicifuga dahurica (Turcz.) Maxim. Their structures
      were elucidated by spectroscopic methods including 1D-NMR, 2D-NMR and HR-MS
      techniques. DPPH method and protective effect on PC12 cells against H2O2-induced
      oxidative damage model were carried to evaluate the antioxidant capability of
      these compounds. Compound 5 showed significant antioxidant activity with IC50
      values 9.33MUM in DPPH assay and compound 2 displayed marked neuro-protective
      effect with 87.65% cell viability at the concentration of 10MUM. Additionally,
      the possible structure-activity relationships of these phenolic compounds were
      tentatively discussed.

PMID- 27693744
TI  - Cornigerin, a new sesqui-lignan from the hepatoprotective fractions of Cynara
      cornigera L.
AB  - The ethanol extract of Cynara cornigera L. was fractionated and the fractions
      were subjected to hepatoprotective assays using Wistar albino rats at a dose of
      500 and 250mg/kg. The liver injury was induced in rats using carbon
      tetrachloride. Biochemical parameters such as aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin
      were estimated as reflections of the liver condition, with silymarin as a
      positive control. Phytochemical investigation and chromatographic separation of
      the hepatoprotective fractions led to the isolation of a new sesqui-lignan namely
      cornigerin (1), along with eight known compounds: apigenin (2), luteolin (3),
      beta-sitosterol glycoside (4), apigenin 7-O-beta-D-glucopyranoside (5), luteolin
      7-O-beta-D-glucopyranoside (6), apigenin-7-O-rutinoside (7), cynarin 1,5-di-O
      caffeoylquinic acid (8), and apigenin-7-O-beta-D-glucuronide (9). This is the
      first report for the isolation of 8 and 9 from this plant.

PMID- 27693745
TI  - Hypolipidaemic and hypoglycaemic activities of polysaccharide from Pleurotus
      eryngii in Kunming mice.
AB  - Therapeutic drugs must be developed to treat hyperglycaemia and hyperlipidaemia,
      which are major risk factors for developing coronary artery diseases and
      atherosclerosis. Pleurotus eryngii is a well-known food resource with functional
      properties in China. In this study, P. eryngii polysaccharide (PEP) was extracted
      with hot water, and its hypolipidaemic and hypoglycaemic activities were
      investigated. KKAy mice were divided into control and PEP groups, which were fed
      with high fat and PEP+high fat, respectively, for 6 weeks. Oral administration of
      PEP decreased body weight gain, the levels of plasma insulin, serum triglyceride,
      cholesterol low-density lipoprotein cholesterol and blasting blood glucose in
      mice. Moreover, PEP diet increased the level of high-density lipoprotein
      cholesterol and liver glycogen. Results indicate that PEP exhibited
      hypolipidaemic and hypoglycaemic activities and could be explored as possible
      therapeutic agents for hyperlipidaemia and hyperglycaemia.

PMID- 27693746
TI  - Protective effect of porphyran isolated from discolored nori (Porphyra yezoensis)
      on lipopolysaccharide-induced endotoxin shock in mice.
AB  - Porphyran, a sulfated polysaccharide, isolated from discolored nori (Porphyra
      yezoensis) (dc-porphyran) and one fraction (F1) purified from dc-porphyran by
      DEAE-chromatography showed the protective effects on LPS-induced endotoxin shock
      in mice. Intraperitoneal (i.p.) treatment with dc-porphyran or F1 (100mg/kg)
      60min prior to i.p. injection of LPS (30mg/kg) completely protected mice from LPS
      lethality. At 10mg/kg concentration, F1 demonstrated more protection than dc
      porphyran. Intravenous (i.v.) challenge of LPS, even at 20mg/kg, was more lethal
      than i.p. administration; i.v. injection of F1 (100mg/kg) with LPS significantly
      improved the survival rate. However, i.v. dc-porphyran (100mg/kg) produced an
      even lower survival rate than that of LPS alone. We examined pro-inflammatory
      mediators such as NO and TNF-alpha in serum. F1 significantly reduced the levels
      of these markers. Additionally, F1 significantly decreased the malondialdehyde
      level in the liver, a marker of oxidative stress, while dc-porphyran had almost
      no effect. Furthermore, F1 significantly decreased the production of TNF-alpha
      and NO in peritoneal exudate cells harvested from LPS-challenged mice, while dc
      porphyran treatment showed a lesser decrease. Our results suggest that porphyran
      isolated from discolored nori, especially F1, is capable of suppressing LPS
      induced endotoxin shock in vivo.

PMID- 27693748
TI  - Emplacing India's "medicities".
AB  - Plans for 'medicities', announced in the Indian press from 2007 onwards, were to
      provide large scale 'one-stop-shops' of super-speciality medical services
      supplemented by diagnostics, education, research facilities, and other aspects of
      healthcare and lifestyle consumption. Placing this phenomenon within the recent
      domestic and global political economy of health, we then draw on recent research
      literatures on place and health to offer an analysis of the narration of these
      new healthcare places given in promotional texts from press media, official
      documents and marketing materials. We consider the implications of such analytic
      undertakings for the understanding of the evolving landscapes of contemporary
      health care in middle-income countries, and end with some reflections on the
      tensions now appearing in the medicity model.

PMID- 27693747
TI  - Modification of chemical reactivity of enzymatic hydrolysis lignin by ultrasound
      treatment in dilute alkaline solutions.
AB  - In this study, we have explored various ultrasound treatment conditions for
      structural modification of enzymatic hydrolysis lignin (EHL) for enhanced
      chemical reactivity. The key structural modifications were characterized by using
      a combination of analytical methods, including, Fourier Transform-Infrared
      spectroscopy (FTIR), Proton Nuclear Magnetic Resonance (1H NMR), Gel permeation
      chromatography (GPC), X-ray photoelectron spectroscopy (XPS), and Folin-Ciocalteu
      (F-C) method. Chemical reactivity of the modified EHL samples was determined by
      both 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and
      their reactivity towards formaldehyde. It was observed that the modified EHL had
      a higher phenolic hydroxyl group content, a lower molecular weight, a higher
      reactivity towards formaldehyde, and a greater antioxidant property. The higher
      reactivity demonstrated by the samples after treatment suggesting that ultrasound
      is a promising method for modifying enzymatic hydrolysis lignin for value-added
      applications.

PMID- 27693749
TI  - Wnt signaling promotes hindgut fate commitment through regulating multi-lineage
      genes during hESC differentiation.
AB  - Wnt signaling plays essential roles in both embryonic pattern formation and
      postembryonic tissue homoestasis. High levels of Wnt activity repress foregut
      identity and facilitate hindgut fate through forming a gradient of Wnt signaling
      activity along the anterior-posterior axis. Here, we examined the mechanisms of
      Wnt signaling in hindgut development by differentiating human embryonic stem
      cells (hESCs) into the hindgut progenitors. We observed severe morphological
      changes when Wnt signaling was blocked by using Wnt antagonist Dkk1. We performed
      deep-transcriptome sequencing (RNA-seq) and identified 240 Wnt-activated genes
      and 2023 Wnt-repressed genes, respectively. Clusters of Wnt targets showed
      enrichment in specific biological functions, such as "gastrointestinal or
      skeletal development" in the Wnt-activated targets and "neural or immune system
      development" in the Wnt-repressed targets. Moreover, we adopted a high-throughput
      chromatin immunoprecipitation and deep sequencing (ChIP-seq) approach to identify
      the genomic regions through which Wnt-activated transcription factor TCF7L2
      regulated transcription. We identified 83 Wnt direct target candidates, including
      the hindgut marker CDX2 and the genes relevant to morphogenesis (MSX1, MSX2,
      LEF1, T, PDGFRB etc.) through combinatorial analysis of the RNA-seq and ChIP-seq
      data. Together, our study identified a series of direct and indirect Wnt targets
      in hindgut differentiation, and uncovered the diverse mechanisms of Wnt signaling
      in regulating multi-lineage differentiation.

PMID- 27693750
TI  - A New Method for Evaluating Actual Drug Release Kinetics of Nanoparticles inside
      Dialysis Devices via Numerical Deconvolution.
AB  - Nanoparticle formulations have found increasing applications in modern therapies.
      To achieve desired treatment efficacy and safety profiles, drug release kinetics
      of nanoparticles must be controlled tightly. However, actual drug release
      kinetics of nanoparticles cannot be readily measured due to technique
      difficulties, although various methods have been attempted. Among existing
      experimental approaches, dialysis method is the most widely applied one due to
      its simplicity and avoidance of separating released drug from the nanoparticles.
      Yet this method only measures the released drug in the medium outside a dialysis
      device (the receiver), instead of actual drug release from the nanoparticles
      inside the dialysis device (the donor). Thus we proposed a new method using
      numerical deconvolution to evaluate actual drug release kinetics of nanoparticles
      inside the donor based on experimental release profiles of nanoparticles and free
      drug solution in the receptor determined by existing dialysis tests. Two computer
      programs were developed based on two different numerical methods, namely least
      square criteria with prescribed Weibull function or orthogonal polynomials as
      input function. The former was used for all analyses in this work while the
      latter for verifying the reliability of the predictions. Experimental data of
      drug release from various nanoparticle formulations obtained from different
      dialysis settings and membrane pore sizes were used to substantiate this
      approach. The results demonstrated that this method is applicable to a broad
      range of nanoparticle and microparticle formulations requiring no additional
      experiments. It is independent of particle formulations, drug release mechanisms,
      and testing conditions. This new method may also be used, in combination with
      existing dialysis devices, to develop a standardized method for quality control,
      in vitro-in vivo correlation, and for development of nanoparticles and other
      types of dispersion formulations.

PMID- 27693751
TI  - Functionalised carbon nanotubes: From intracellular uptake and cell-related
      toxicity to systemic brain delivery.
AB  - Carbon nanotubes (CNTs) have long been regarded as promising carriers in
      biomedicine. Due to their high surface area and unique needle-like structure,
      CNTs are uniquely equipped to carry therapeutic molecules across biological
      membranes and, therefore, have been widely researched for use in theranostic
      applications. The attractive properties of the CNTs entice also their use in the
      brain environment. Cutting edge brain-specific therapies, capable of
      circumventing the physical and biochemical blockage of the blood-brain barrier,
      could be a precious tool to tackle brain disorders. With an increasing number of
      applications and expanding production, the effects of direct and indirect
      exposure to CNTs on cellular and molecular levels and more globally the general
      health, must be carefully assessed and limited. In this chapter, we review the
      most recent trends on the development and application of CNT-based
      nanotechnologies, with a particular focus on the carrier properties, cell
      internalisation and processing, and mechanisms involved in cell toxicity. Novel
      approaches for CNT-based systemic therapeutic brain delivery following
      intravenous administration are also reviewed. Moreover, we highlight fundamental
      questions that should be addressed in future research involving CNTs, aiming at
      achieving its safe introduction into the clinics.

PMID- 27693752
TI  - A stabilized peptide ligand for multifunctional glioma targeted drug delivery.
AB  - Peptide ligands consisting of l-amino acids are subject to proteolysis in vivo.
      When modified on the surface of nanocarriers, those peptide ligands would readily
      degrade and the targeting efficacy is significantly attenuated. It has received
      increasing scrutiny to design stable peptide ligands for targeted drug delivery.
      Here, we present the design of a stable peptide ligand by the formation of a head
      to-tail amide bond as an example. Even though the linear l-peptide A7R (termed
      LA7R) can bind specifically to vascular endothelial growth factor receptor 2
      (VEGFR2) and neuropilin-1 (NRP-1) that are overexpressed on glioma cells,
      neovasculature and glioma vasculogenic mimicry (VM), the tumor-homing capacity of
      LA7R is greatly impaired in vivo due to proteolysis (e.g. in the serum). A cyclic
      A7R (cA7R) peptide was identified by computer-aided peptide design and
      synthesized with high yield by combining solid phase peptide synthesis and native
      chemical ligation. The binding of cA7R to both receptors was theoretically and
      experimentally assessed. In our simulated model hydrophobic and ionic
      interactions dominated the binding of LA7R to receptors. It is very interesting
      that cA7R adopting a different structure from LA7R retained high binding
      affinities to receptors without affecting the hydrophobic and ionic interactions.
      After head-to-tail cyclization by the formation of an amide bond, cA7R exhibited
      exceptional stability in mouse serum. Either cA7R or LA7R was conjugated on the
      surface of doxorubicin (DOX) loaded liposomes (cA7R-LS/DOX or LA7R-LS/DOX). The
      results of in vitro cellular assays indicated that cA7R-LS/DOX not only displayed
      stronger anti-proliferative effect against glioma cells, but also demonstrated to
      be more efficient in destruction of VM and HUVEC tubes in comparison to LA7R
      LS/DOX and plain liposomes (LS/DOX, without peptide conjugation). cA7R
      conjugation could achieve significantly higher accumulation of liposomes in
      glioma than did LA7R conjugation, which in turn, cA7R-LS/DOX could substantially
      suppress subcutaneous tumor growth when compared with other DOX formulations
      (free DOX, LS/DOX and LA7R-LS/DOX). The designed cyclic A7R exhibited the
      capability of targeting glioma cells, neovasculature and VM simultaneously in
      vivo. Considering the ease of synthesis, high binding affinity to receptors and
      increased stability of cA7R peptide in the present study, the design of head-to
      tail cyclized peptides by the formation of amide bond based on computer-aided
      peptide design presents an alternative method to identify proteolytically stable
      peptide ligands.

PMID- 27693753
TI  - Viability and infectivity of fresh and cryopreserved Nosema ceranae spores.
AB  - The microsporidium fungus Nosema ceranae is an intracellular parasite that
      infects the midgut of the honey bee, Apis mellifera. A major limitation of
      research on N. ceranae is that the fungus is non-culturable and thus studying it
      depends on the seasonal availability of Nosema spores. Also, spore viability and
      infectivity can vary considerably, and thus there is a need for reliable methods
      for determining those traits. This study examined different conditions for N.
      ceranae spore cryopreservation at -70 degrees C, assessing spore viability and
      infectivity. Viability was determined by a staining procedure counting total
      spores numbers with bright field microscopy and un-viable spore numbers with the
      fluorescent dye, propidium iodide. Spore infectivity was determined with a
      dilution inoculation assay. Infectivity was dependent on the inoculum dose for
      the proportion of bees with detectable Nosema infections based on the number of
      spores per bee at 18days after inoculation; 4000 spores per bee or higher were
      needed to get approx. 100% of the inoculated bees infected. The median infective
      dose (ID50) was 149 spores per bee, and the minimum dose capable of causing a
      detectable infection was 1.28 spores. The proportion of N. ceranae infected bees
      correlated significantly with the number of spores per bee (r=0.98, P<0.0001). N.
      ceranae spores cryopreserved in water or 10% glycerol did not differ in viability
      compared to fresh spores, but lost infectivity when inoculated into bees. This
      study shows that while cryopreservation of N. ceranae spores can preserve
      viability, the spores can have reduced infectivity.

PMID- 27693755
TI  - Development and validation of a rapid and sensitive UPLC-MS/MS method for
      quantification of kukoamine B in human plasma: Application to a clinical
      pharmacokinetic study.
AB  - A rapid, accurate and robust method was firstly developed using ultra-performance
      liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay to quantify
      kukoamine B, which is a novel drug under clinical development for the treatment
      of sepsis, in human plasma. Solid-phase extraction (SPE) was used to extract
      kukoamine B from human plasma. The extracts were separated on a Waters Acquity
      HSS T3 column (2.1*50mm i.d., 1.8MUm) with a gradient elution method, using
      mobile phases of A (formic acid-water (1:1000, v/v)) and B(formic acid-methanol
      (1:1000, v/v)). Kukoamine B and internal standard (5-deuterated isotope kukoamine
      B) were detected under the multiple-reaction monitoring mode by an API 5500
      triple quadrupole mass spectrometer with electrospray ionization. The method
      showed good linearity from 0.100 to 50.0ng/mL according to 1/x2 weighted linear
      regression analysis. Inter- and intra-batch precision of kukoamine B were less
      than 15% and the accuracy was within 85-115%. The extraction recoveries and
      matrix effect of kukoamine B at three concentration levels were consistent. The
      sensitivity, specificity and stabilities under various conditions were validated.
      In conclusion, the validation results showed that this method was rapid,
      accurate, robust and can successfully fulfill the requirement of clinical
      pharmacokinetic study of kukoamine B mesylate in Chinese healthy subjects.

PMID- 27693756
TI  - NQO1 and CYP450 reductase decrease the systemic exposure of rifampicin-quinone
      and mediate its redox cycle in rats.
AB  - Rifampicin (RIF) is used in regimens for infections caused by Mycobacteria
      accompanied by serious adverse reactions. Rifampicin-quinone (RIF-Q) is a major
      autoxidation product of RIF. It is not clear whether RIF-Q plays a role in RIF
      induced adverse reactions. Investigation of the systemic exposure of RIF-Q is
      helpful to better understand the role of RIF-Q in RIF induced adverse reactions.
      In this study, a simple and reproducible high performance liquid chromatography
      mass spectrometry (LC-MS) method involving a procedure to prevent the RIF from
      oxidation for simultaneous quantification of RIF and RIF-Q in rat plasma has been
      developed and validated, and applied to elucidate the systemic exposure of RIF-Q
      in rats. The pharmacokinetics data showed that the systemic exposure of RIF-Q was
      very low (0.67% of RIF, AUC0-24) in rats after oral administration of RIF.
      However, RIF-Q may undergo the redox cycle in vivo by the evidence that the
      majority of RIF-Q was reduced to RIF after an oral dose of RIF-Q. Pretreatment
      with the NAD(P)H: quinone oxidoreductase 1 (NQO1) specific inhibitor dicoumarol
      and/or cytochrome P450 reductase (CPR) inhibitor diphenyleneiodonium suppressed
      the redox cycle and significantly increased the systemic exposure of RIF-Q. The
      inhibitors also attenuated the redox cycle induced reactive oxygen species
      formation and cytotoxicity in RIF-Q-treated HepG2 cells. These results indicate
      that NQO1 and CPR play an important role in redox cycle of RIF-Q and may thus
      contribute to RIF-induced adverse reactions.

PMID- 27693754
TI  - Resolving colocalization of bacteria and metal(loid)s on plant root surfaces by
      combining fluorescence in situ hybridization (FISH) with multiple-energy micro
      focused X-ray fluorescence (ME MUXRF).
AB  - Metal(loid)-contamination of the environment due to anthropogenic activities is a
      global problem. Understanding the fate of contaminants requires elucidation of
      biotic and abiotic factors that influence metal(loid) speciation from molecular
      to field scales. Improved methods are needed to assess micro-scale processes,
      such as those occurring at biogeochemical interfaces between plant tissues,
      microbial cells, and metal(loid)s. Here we present an advanced method that
      combines fluorescence in situ hybridization (FISH) with synchrotron-based
      multiple-energy micro-focused X-ray fluorescence microprobe imaging (ME MUXRF) to
      examine colocalization of bacteria and metal(loid)s on root surfaces of plants
      used to phytostabilize metalliferous mine tailings. Bacteria were visualized on a
      small root section using SytoBC nucleic acid stain and FISH probes targeting the
      domain Bacteria and a specific group (Alphaproteobacteria, Gammaproteobacteria,
      or Actinobacteria). The same root region was then analyzed for elemental
      distribution and metal(loid) speciation of As and Fe using ME MUXRF. The FISH and
      ME MUXRF images were aligned using ImageJ software to correlate microbiological
      and geochemical results. Results from quantitative analysis of colocalization
      show a significantly higher fraction of As colocalized with Fe-oxide plaques on
      the root surfaces (fraction of overlap 0.49+/-0.19) than to bacteria (0.072+/
      0.052) (p<0.05). Of the bacteria that colocalized with metal(loid)s,
      Actinobacteria, known for their metal tolerance, had a higher correlation with
      both As and Fe than Alphaproteobacteria or Gammaproteobacteria. This method
      demonstrates how coupling these micro-techniques can expand our understanding of
      micro-scale interactions between roots, metal(loid)s and microbes, information
      that should lead to improved mechanistic models of metal(loid) speciation and
      fate.

PMID- 27693757
TI  - Impact of mono- and poly-ester fractions on polysorbate quantitation using mixed
      mode HPLC-CAD/ELSD and the fluorescence micelle assay.
AB  - Determination of excipient content in drug formulation is an important aspect of
      pharmaceutical formulation development and for analytical testing of the
      formulation. In this study, the influence of polysorbate subspecies, in
      particular mono- and poly-esters, for determining polysorbate (PS) content were
      investigated by comparing three of the most widely used PS quantitation
      approaches, the Fluorescence Micelle Assay (FMA) and Mixed-Mode High Performance
      Liquid Chromatography coupled with Charged Aerosol Detection (MM-CAD) or
      Evaporative Light Scattering Detection (MM-ELSD). FMA and MM-CAD were employed to
      investigate the quantitation behavior of PS20 and PS80 subspecies and
      corresponding degradation products in placebo formulations using forced
      degradation conditions at 40 degrees C for up to 12 weeks. While both methods
      allowed accurate and comparable quantification of neat PS at the beginning of
      stress studies, pronounced differences in content determination between the
      methods were observed at later time points, which were attributable to
      substantial differences in the contribution of individual mono- and poly-esters
      to the overall quantitation results. It was particularly surprising to find that
      the main component of PS20, polyoxyethylene sorbitan monolaurate, did not show a
      signal at the studied concentration using FMA. Moreover, the degradation of
      polysorbate poly-esters, was reflected much stronger in FMA than MM-CAD results.
      Additional experiments employing chemical oxidation and base hydrolysis to
      degrade PS20, quantified by FMA and MM-ELSD, also show preferential reduction in
      certain subspecies depending on the degradation pathway involved. For PS20
      degraded by chemical oxidation, quantitation results were lower for FMA than MM
      ELSD, while the opposite trend was observed with base hydrolysis.

PMID- 27693758
TI  - From chemical consistency to effective consistency in precise quality
      discrimination of Sophora flower-bud and Sophora flower: Discovering efficacy
      associated markers by fingerprint-activity relationship modeling.
AB  - Chromatographic fingerprint has been extensively used as a comprehensive approach
      for quality evaluation of herbal medicines (HMs). However, similar chemical
      profiles do not always mean similar efficacies. The present work, taking Sophora
      flower-bud and Sophora flower as a typical case, attempts to develop a rational
      strategy based on fingerprint-activity relationship modeling to realize quality
      evaluation from chemical consistency to effective consistency. A total of 57
      batches of Sophora samples were collected and their antioxidant and hyaluronidase
      inhibitory activities were measured. Chemical fingerprints were established by
      high performance liquid chromatography (HPLC) coupled with photodiode array (PDA)
      detector and quadrupole time-of-flight mass spectrometry (Q-TOF MS), and
      similarity analyses were calculated based on eight common characteristic peaks.
      Subsequently, three principal bioactive markers were discovered by correlating
      biological effects with chemical fingerprints via partial least squares
      regression (PLSR) and back propagation-artificial neural network modeling (BP
      ANN). The selected markers were quantified by the 'single standard to determine
      multi-components' method, and then the quantitative data as well as their
      bioactive properties were subjected to principal component analysis to generate
      two clear-cut groups. This study not only demonstrates the necessity of effective
      consistency besides chemical consistency in the quality evaluation of HMs, but
      also provides an applicable strategy to screen out efficacy-associated markers by
      fingerprint-activity relationship modeling.

PMID- 27693759
TI  - Design and evaluation of a park prescription program for stress reduction and
      health promotion in low-income families: The Stay Healthy in Nature Everyday
      (SHINE) study protocol.
AB  - BACKGROUND: Contact with nature improves human health; stress reduction is a
      mediating pathway. Stay Healthy in Nature Everyday (SHINE) is a stress reduction
      and health promotion intervention for low-income families at an urban Federally
      Qualified Health Center. We plan to evaluate two service-delivery models for
      SHINE and present here the intervention design and evaluation protocol. METHODS:
      Behavioral change theory and environmental education literature informed the
      intervention. Outcomes were selected after review of the literature and field
      tested procedures to determine what was feasible and ethical in a busy clinic
      serving vulnerable populations. DESIGN: We designed a randomized controlled trial
      to examine two levels of intensity in behavioral counseling about the health
      benefits of nature. Dyads consisting of a caregiver and a child aged 4 to 18 who
      access our pediatric primary care center are eligible. All dyads receive a
      pediatrician's recommendation to visit parks to experience nature and written
      resources (a "park prescription"). The intervention group receives added case
      management and an invitation to three group outings into nature with
      transportation, meals and activities provided. Primary outcomes measured at
      baseline, one month and three months post-enrollment are caregiver stress
      measured by PSS-10 score and salivary alpha-amylase; secondary outcomes are park
      prescriptions adherence, physical activity recorded by pedometer and journaling,
      loneliness, family cohesion and affinity to nature as measured by a validated
      scales. Both groups receive incentives to participation. DISCUSSION: Our
      intervention represents a feasible integration of recent research findings on the
      health benefits of nature and primary care practice.

PMID- 27693760
TI  - To the Editor- Novel method for earlier detection of phrenic nerve injury during
      cryoballoon applications for electrical isolation of pulmonary veins in patients
      with atrial fibrillation.

PMID- 27693761
TI  - Responses of He-Ne laser irradiation on agronomical characters and chlorogenic
      acid content of brinjal (Solanum melongena L.) var. Mattu Gulla.
AB  - Exposure to laser irradiation on seeds brings about the changes in agronomical
      characteristics of the plants. Solanum melongena L. var. Mattu Gulla, a variety
      of brinjal is of high economic value due to its unique colour and flavour. The
      aim of the study was to understand the influence of Helium-Neon (He-Ne) laser
      irradiation on agronomical characters of Solanum melongena L. var. Mattu Gulla in
      the field conditions. Various growth characteristics including seed germination
      percentage, survival rate, plant height, number of branches, and flowers and
      fruits were estimated during different developmental stages of the brinjal. In
      addition, the chlorogenic acid content of fruits obtained from the laser
      irradiated seeds were quantified using reversed-phase high-performance liquid
      chromatography (RP- HPLC). The plants from the seeds irradiated with different
      doses (20, 25 and 30J/cm2) of He-Ne laser showed significant enhancement on the
      growth characteristics when compared to the non-irradiated control groups. He-Ne
      laser irradiation also improved the yield characteristics of the plants
      significantly in in vivo conditions in comparison with control group. 3-(4, 5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed
      using methanolic extract of matured fruit of Mattu Gulla on HepG2 and fibroblast
      cell lines. The IC50 values of fruit extract from laser irradiated groups were
      found to be similar to non-irradiated control groups. Chlorogenic acid content
      was found to be higher in 20J/cm2 and lower in 30J/cm2 treated fruit tissue. The
      current study thus elucidates the role of He-Ne laser as a biostimulator on
      brinjal var. Mattu Gulla not only in the in vitro conditions but also in the in
      vivo field conditions.

PMID- 27693762
TI  - The characterization of 1-(4-bromophenyl)-5-phenyl-1H-1,2,3-triazole on acute
      toxicity, antimicrobial activities, photophysical property, and binding to two
      globular proteins.
AB  - 1-(4-Bromophenyl)-5-phenyl-1H-1,2,3-triazole (BPT) was a newly synthesized
      compound. The acute toxicities of BPT to mice by intragastric administration have
      been determined and the result indicates that the intragastric administration of
      BPT did not produce any significant toxic effect on Kunming strain mice. It is
      also evaluated for the antimicrobial activity of BPT against three kinds of plant
      mycoplasma, Fusarium Wilt (race 4), Colletotrichum gloeosporioides Penz. and
      Xanthomonas oryzae by different method in vitro. The compound exhibited distinct
      inhibitory activities against Fusarium Wilt (race 4) and Colletotrichum
      gloeosporioides Penz. by mycelium growth rate test and the values of EC50 were
      29.34 and 12.53MUg/mL respectively. And BPT had also the most potent inhibitory
      activities against Xanthomonas oryzae when compared with that of control drugs by
      the agar well diffusion method. In addition, the structural and photophysical
      properties of BPT including ionization energy, electron affinities, and
      theoretical spectrum was studied by quantum-chemical methods. Then the
      interaction of BPT with two kinds of globular proteins, human immunoglobulin
      (HIg) and bovine hemoglobin (BHg) was investigated by using UV-vis absorption
      spectra, synchronous fluorescence, 3D fluorescence spectra, and fluorescence
      titration in combination with molecular modeling. UV-vis absorption, 3D and
      synchronous fluorescence measurements show that BPT has influence on the
      microenvironment surrounding HIg or BHg in aqueous solution and the fluorescence
      experiments show that BPT quenches the fluorescence intensity of HIg or BHg
      through a static mechanism. The binding parameters including the binding
      constants, the number of binding site and average binding distance between BPT
      and HIg or BHg at different temperatures were calculated. The thermodynamic
      parameters suggest that the hydrophobic interaction is the predominant
      intermolecular forces in stabilizing the BPT-HIg or BPT-BHg complex. Molecular
      docking was performed to reveal that the BPT moiety binds to the hydrophobic
      cavity of HIg or BHg and they are in good agreement with the spectroscopic
      measurements.

PMID- 27693763
TI  - Body Image in Primary Schools: A pilot evaluation of a primary school
      intervention program designed by teachers to improve children's body
      satisfaction.
AB  - Body Image in the Primary School (Hutchinson & Calland, 2011) is a body image
      curriculum that is widely available but has not yet been evaluated. This study
      evaluates a set of 6 of the 49 available lessons from this curriculum. Seventy
      four girls and 70 boys aged 9-10 were recruited from four primary schools in the
      UK. Schools were randomly allocated into the intervention condition, where
      students received 6hours of body image lessons, or to lessons as normal. Body
      esteem was significantly higher among girls in the intervention group, compared
      to the control group, immediately post intervention, and at 3-month follow-up.
      Moreover, girls with lowest levels of body esteem at baseline reported the
      largest gains. Internalization was significantly lower among boys in the control
      group compared to the intervention group at 3-month follow-up. The pattern of
      results among the control group raises interesting issues for intervention
      evaluation.

PMID- 27693764
TI  - Improving patient safety reporting with the common formats: Common data
      representation for Patient Safety Organizations.
AB  - Medical errors and patient safety issues remain a significant problem for the
      healthcare industry in the United States. The Institute of Medicine report To Err
      is Human reported that there were as many as 98,000 deaths per year due to
      medical error as of 1999. Many authors and government officials believe that the
      first step on the path to improvement in patient safety is more comprehensive
      collection and analysis of patient safety events. The belief is that this will
      enable safety improvements based on data showing the nature and frequency of
      events that occur, and the effectiveness of interventions. This systematization
      of healthcare practice can be a step in the right direction toward a value based,
      safety conscious and effective healthcare system. To help standardize this
      reporting and analysis, AHRQ created Common Formats for Patient Safety data
      collection and reporting. This manuscript describes the development of patient
      safety reporting and learning through the Patient Safety Organizations (PSO)s and
      the Common Formats and gives readers an overview of how the system is expected to
      function and the breadth of development of the Common Formats to date.

PMID- 27693765
TI  - Two novel mitochondrial tRNA mutations, A7495G (tRNASer(UCN)) and C5577T
      (tRNATrp), are associated with seizures and cardiac dysfunction.
AB  - We describe here two novel mitochondrial mutations associated with a complex
      mitochondrial encephalopathy. An A to G transition at position 7495 (MT-TS1 (MT
      tRNSer(UCN))) was identified at 83% heteroplasmy in the muscle of a four year old
      female with ptosis, hypotonia, seizures, and dilated cardiomyopathy (Case 1). A
      homoplasmic C to T transition at position 5577 (MT-TW (MT-tRNATrp)) was found in
      a twenty-four year old woman with exercise intolerance, mild muscle weakness,
      hearing loss, seizures, and cognitive decline (Case 2). The phenotypic
      information provided here will assist in phenotype-genotype correlations should
      additional patients be reported in the future. The mutations can be added to the
      database of mitochondrial DNA variations in conserved regions which result in
      clinically diverse phenotypes with the shared markers of mitochondrial disease.

PMID- 27693766
TI  - Characteristics of Rosai-Dorfman Disease Primarily Involved in the Central
      Nervous System: 3 Case Reports and Review of Literature.
AB  - OBJECTIVE: This study aimed to summarize the clinical characteristics of Rosai
      Dorfman disease primarily involving the central nervous system and to explore
      diagnosis and treatment. METHODS: We analyzed the clinical, imaging, and
      pathologic characteristics; treatment; and prognosis in 3 cases of Rosai-Dorfman
      disease primarily involving the central nervous system. We also performed a
      literature review. RESULTS: The largest of multiple intracranial lesions was
      totally resected, and steroid administration and radiotherapy were performed in
      phases for the remaining lesions. During the 1-year follow-up period, the excised
      lesion did not recur, and no obvious variations were observed in the other
      lesions. Subtotal resection was performed of the largest of another group of
      multiple intracranial lesions, and the residual did not show any obvious
      variations during the 1-year follow-up period. The isolated lesion was totally
      resected and did not recur during a 2-year follow-up period. CONCLUSIONS: Rosai
      Dorfman disease with multiple lesions primarily involving the central nervous
      system is rare. Imaging characteristics are similar to meningiomas, and the
      pathological features include lymphocytes and plasma cells reaching tissue cells
      with large volume and abundant cytoplasm. Surgery is the preferred treatment, as
      the effects of steroid administration and radiotherapy are not apparent.

PMID- 27693767
TI  - Intracranial Facial Nerve Schwannomas: Current Management and Review of
      Literature.
AB  - BACKGROUND: Facial nerve schwannomas are rare, benign, nerve-sheath tumors. They
      can occur in any segment of the facial nerve and often clinically and
      radiographically mimic the common vestibular schwannoma when extending into the
      cerebellopontine angle. The optimal treatment strategy for intracranial facial
      nerve schwannomas remains controversial. METHODS: We review the literature and
      discuss the natural history, clinical features, diagnosis and current management
      of facial nerve schwannoma. RESULTS: Complete tumor resection with facial nerve
      preservation can be achieved in fewer cases. In most cases, the affected segment
      of facial nerve must be removed if the goal is to achieve complete tumor section.
      Regardless of type of facial nerve repair, patients can expect no better than an
      eventual HB grade III palsy. Stereotactic radiosurgery has good results in tumor
      control and facial function outcome. CONCLUSIONS: Treatment for intracranial
      facial nerve schwannomas depends on clinical presentation, tumor size,
      preoperative facial, and hearing function. Conservative management is recommended
      for asymptomatic patients with small tumors. Stereotactic radiosurgery may be an
      option for smaller and symptomatic tumors with good facial function. If tumor is
      large or the patient has facial paralysis, surgical resection should be
      indicated. If preservation of the facial nerve is not possible, total resection
      with nerve grafting should be performed for those patients with facial paralysis,
      whereas subtotal resection is best for those patients with good facial function.

PMID- 27693768
TI  - The Role of Intraoperative Cerebral Angiography in Transorbital Intracranial
      Penetrating Trauma: A Case Report and Literature Review.
AB  - BACKGROUND: Transorbital intracranial penetrating trauma with a retained
      intracranial foreign body is a rare event lacking a widely accepted diagnostic
      and therapeutic algorithm. Intraoperative catheter angiography (IOA) has been
      advocated by some authorities to rule out cerebrovascular injury before and/or
      after removal of the object, but no standard of care currently exists. CASE
      DESCRIPTION: A 19-year-old man was involved in a construction site accident
      whereby a framing nail penetrated the left globe, traversed the lateral bony
      orbit, and terminated in the midtemporal lobe. No hematoma or injury to the
      middle cerebral arteries (MCAs) was apparent on noncontrast head computed
      tomography (CT) or CT angiography, respectively. The foreign body was removed in
      the operating room under direct visualization after a frontotemporal craniotomy
      without incident. No significant venous or arterial bleeding was encountered. All
      visualized MCA branches appeared intact. Indocyanine green videoangiography
      performed immediately after object removal showed adequate filling of the MCA
      branches. Given these uneventful clinical and radiographic findings, IOA was not
      performed. Postoperative head CT and CT angiography showed no obvious
      neurovascular injury. On postoperative day 2, the patient was noted to have an
      expressive aphasia. Cerebral angiography showed absent antegrade filling of the
      angular artery with some retrograde perfusion. Magnetic resonance imaging
      confirmed an ischemic infarction in the midtemporal lobe. The patient's
      expressive aphasia improved to near baseline during his hospitalization and he
      made an excellent clinical recovery. CONCLUSIONS: In transorbital intracranial
      penetrating trauma with a retained intracranial object, we advocate microsurgical
      removal of the object under direct visualization followed immediately by IOA. IOA
      should be strongly considered even in the setting of minimal intraoperative
      bleeding and normal findings on videoangiography (a course of action that was not
      followed in the present case). Given that CT angiography and intraoperative
      videoangiography may miss a potentially treatable traumatic arterial injury, IOA
      can help determine whether cerebral revascularization may be necessary.

PMID- 27693769
TI  - Outcomes and Complications After Endovascular Treatment of Brain Arteriovenous
      Malformations: A Prognostication Attempt Using Artificial Intelligence.
AB  - PURPOSE: To identify factors influencing outcome in brain arteriovenous
      malformations (BAVM) treated with endovascular embolization. We also assessed the
      feasibility of using machine learning techniques to prognosticate and predict
      outcome and compared this to conventional statistical analyses. METHODS: A
      retrospective study of patients undergoing endovascular treatment of BAVM during
      a 22-year period in a national neuroscience center was performed. Clinical
      presentation, imaging, procedural details, complications, and outcome were
      recorded. The data was analyzed with artificial intelligence techniques to
      identify predictors of outcome and assess accuracy in predicting clinical outcome
      at final follow-up. RESULTS: One-hundred ninety-nine patients underwent treatment
      for BAVM with a mean follow-up duration of 63 months. The commonest clinical
      presentation was intracranial hemorrhage (56%). During the follow-up period,
      there were 51 further hemorrhagic events, comprising spontaneous hemorrhage (n =
      27) and procedural related hemorrhage (n = 24). All spontaneous events occurred
      in previously embolized BAVMs remote from the procedure. Complications included
      ischemic stroke in 10%, symptomatic hemorrhage in 9.8%, and mortality rate of
      4.7%. Standard regression analysis model had an accuracy of 43% in predicting
      final outcome (mortality), with the type of treatment complication identified as
      the most important predictor. The machine learning model showed superior accuracy
      of 97.5% in predicting outcome and identified the presence or absence of nidal
      fistulae as the most important factor. CONCLUSIONS: BAVMs can be treated
      successfully by endovascular techniques or combined with surgery and radiosurgery
      with an acceptable risk profile. Machine learning techniques can predict final
      outcome with greater accuracy and may help individualize treatment based on key
      predicting factors.

PMID- 27693770
TI  - In vitro antiprotozoal activity and cytotoxicity of extracts and isolated
      constituents from Greenwayodendron suaveolens.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Nkundo people (Nkundo area of Bolongo, Mai
      Ndombe district, Bandundu Province, DR Congo) use various plant parts of the tree
      Greenwayodendron suaveolens (Engl. & Diels) Verdc. (syn. Polyalthia suaveolens
      Engl. & Diels) (Annonaceae) against malaria, but its antiprotozoal constituents
      are not known. MATERIALS AND METHODS: The crude 80% ethanol extract from the
      fruits, leaves, root bark and stem bark and 16 fractions were assessed in vitro
      for their antiprotozoal activity against Trypanosoma brucei brucei, T. cruzi,
      Leishmania infantum and the chloroquine and pyrimethamine-resistant K1 strain of
      Plasmodium falciparum (Pf-K1). Their cytotoxic effects were evaluated against MRC
      5 cells. Active constituents were isolated by chromatographic means, identified
      using spectroscopic methods, and evaluated in the same assays. RESULTS: The root
      bark extract showed the highest activity against P. falciparum K1 (IC50
      0.26ug/mL) along with the stem bark alkaloid fraction (IC50 0.27ug/mL). The root
      bark alkaloid fraction had a pronounced activity against all selected protozoa
      with IC50 values <1ug/mL. The 90% methanol fractions of the different plant parts
      showed a pronounced activity against P. falciparum K1, with IC50 values ranging
      between 0.36ug/mL and 0.69ug/mL. Four constituents were isolated: the triterpenes
      polycarpol, and dihydropolycarpol, the latter one being reported for the first
      time from nature, and the alkaloids polyalthenol and N-acetyl-polyveoline. They
      were active to a various degree against one or more protozoa, mostly accompanied
      by cytotoxicity. The highest selectivity was observed for N-acetyl-polyveoline
      against P. falciparum K1 (IC50 2.8uM, selectivity index 10.9). CONCLUSIONS: These
      results may explain at least in part the traditional use of this plant species
      against parasitic diseases such as malaria in DR Congo.

PMID- 27693771
TI  - Exploring the antimalarial potential of whole Cymbopogon citratus plant therapy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (lemon grass) has been used
      in traditional medicine as an herbal infusion to treat fever and malaria.
      Generally, whole plant extracts possess higher biological activity than purified
      compounds. However, the antimalarial activity of the whole C. citratus plant has
      not been experimentally tested. AIM OF THE STUDY: To evaluate the antimalarial
      activity of an herbal infusion and the whole Cymbopogon citratus plant in two
      experimental models of malaria. MATERIAL AND METHODS: The plant was dried for 10
      days at room temperature and was then milled and passed through brass sieves to
      obtain a powder, which was administered to CBA/Ca mice with a patent Plasmodium
      chabaudi AS or P. berghei ANKA infection. We analysed the effects of two
      different doses (1600 and 3200mg/kg) compared with those of the herbal infusion
      and chloroquine, used as a positive control. We also assessed the prophylactic
      antimalarial activities of the whole C. citratus plant and the combination of the
      whole plant and chloroquine. RESULTS: The C. citratus whole plant exhibited
      prolonged antimalarial activity against both P. chabaudi AS and P. berghei ANKA.
      The low dose of the whole C. citratus plant displayed higher antimalarial
      activity than the high dose against P. berghei ANKA. As a prophylactic treatment,
      the whole plant exhibited higher antimalarial activity than either the herbal
      infusion or chloroquine. In addition, the combination of the whole C. citratus
      plant and chloroquine displayed higher activity than chloroquine alone against P.
      berghei ANKA patent infection. CONCLUSIONS: We demonstrated the antimalarial
      activity of the whole C. citratus plant in two experimental models. The whole C.
      citratus plant elicited higher anti-malarial activity than the herbal infusion or
      chloroquine when used as a prophylactic treatment. The antimalarial activity of
      the whole C. citratus plant supports continued efforts towards developing whole
      plant therapies for the management of malaria and other infectious diseases
      prevalent in resource-poor communities.

PMID- 27693772
TI  - Toxic polyacetylenes in the genus Bupleurum (Apiaceae) - Distribution, toxicity,
      molecular mechanism and analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The genus Bupleurum includes approximately 200
      species that are widely distributed in the Northern Hemisphere, Eurasia and North
      Africa. Certain species of this genus have long been used as antiphlogistic,
      antipyretic and analgesic agents in traditional folk medicine. As described in
      the Chinese Pharmacopoeia, the roots of Bupleurum chinense DC. and B.
      scorzonerifolium Willd. are the herbal materials that compose Chaihu (Radix
      Bupleuri), a well-known TCM herb. AIM OF THE REVIEW: This review aims to provide
      up-to-date and comprehensive information regarding the distribution, toxicity,
      molecular mechanism and relatively new methods for the qualitative and
      quantitative determination of polyacetylenes in different Bupleurum species.
      METHOD: The information needed for this paper were sourced from publishing sites
      such as Elsevier, science Direct, PubMed; electronic search engines such as
      Scopus and Web of Science, Google scholar; other scientific database sites for
      chemicals such as ChemSpider, PubChem, SciFinder, and also from on line books.
      RESULTS: Polyacetylenes, which are widely distributed in genus Bupleurum of the
      Apiaceae family, have high toxicity. Among polyacetylenes, bupleurotoxin,
      acetylbupleurotoxin and oenanthotoxin have strong neurotoxicity. Through previous
      research, it was found that the toxicity of Bupleurum polyacetylenes manifested
      as epileptic seizures, with the target of toxicity being the brain. The
      neurotoxicity of polyacetylenes exhibits a relationship with the gamma
      aminobutyric acid (GABA) receptor pathway, and polyacetylenes have been shown to
      inhibit GABA-induced currents (IGABA) in a competitive manner. CONCLUSIONS: The
      plants of genus Bupleurum have been used in traditional medicine for thousands of
      years. However, certain species of this genus are poisonous, and it was
      attributed to the high content of polyacetylenes. The present review indicates
      that certain polyacetylenes in the genus Bupleurum have highly neurotoxic
      effects. The major challenge with regard to toxic polyacetylenes is to test their
      neurotoxic effects in vivo as well as in further preclinical studies, which will
      require large amounts of purified polyacetylenes. More reference substances
      should be prepared, and sophisticated analytical technologies should be developed
      to comprehensively assess the quality of Radix Bupleuri herbs. These
      investigations will be helpful for further utilization of the plants of genus
      Bupleurum.

PMID- 27693773
TI  - Add-on effect of crude rhubarb to somatostatin for acute pancreatitis: A meta
      analysis of randomized controlled trials.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is one of the common herbs used in
      traditional Chinese complex prescriptions for the treatment of various
      inflammatory diseases. We sought to determine the add-on effect of crude rhubarb
      to somatostatin in patients with acute pancreatitis by conducting a meta
      analysis. MATERIALS AND METHODS: We searched the Pubmed, EMBASE, Cochrane
      Library, CNKI, Wanfang, VIP databases up to November 2015. Randomized controlled
      trials (RCTs) comparing crude rhubarb plus somatostatin to somatostatin alone for
      acute pancreatitis were included. Risk ratio (RR) or weighted mean difference
      (WMD) with their 95% confidence interval (CI) was calculated between with and
      without crude rhubarb therapy. RESULTS: A total of 19 RCTs involving 1161
      patients were identified. Compared with somatostatin alone, crude rhubarb plus
      somatostatin significantly reduced the total complications (RR 0.55; 95% CI 0.41
      0.73) and APACHE II scores (WMD -1.16; 95% CI -1.91 to -0.41) as well as
      shortened the duration of elevated serum amylase (WMD -2.01 days; 95% CI -2.57 to
      -1.44), duration of abdominal pain (WMD -1.33 days; 95% CI -1.61 to -1.05), the
      first defecation time (WMD -2.27 days; 95% CI -3.06 to -1.47), and duration of
      hospital stay (WMD -6.70 days; 95% CI -8.81 to -4.60). However, there were no
      significant differences in total mortality rates (RR 0.61; 95% CI 0.34 to 1.12)
      between two groups. CONCLUSIONS: Crude rhubarb as adjuvant therapy to
      somatostatin appears to have additional benefits in patients with acute
      pancreatitis. However, interpretation of these results should be cautioned due to
      the methodological flaws.

PMID- 27693775
TI  - Myrtus communis L. and its application in treatment of Recurrent Aphthous
      Stomatitis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In Iranian Traditional Medicine, M. communis is a
      famous plant in treatment of oral ulcers and "Gholaa"- the ancient name of
      aphthous. OBJECTIVE: The aim of this review is to create a bridge between the
      traditional claims about the application of M. communis in treatment of "Gholaa"
      and its prescription for aphthous, the current form of "Gholaa" in modern
      medicine METHODS: We extracted the information about the application of M.
      communis in treatment of aphthous from different resources including Google
      scholar, Pubmed, ScienceDirect, Springer, ethnobotanical, the traditional books
      from Traditional Medicine Tehran University of Medical Sciences. RESULTS: In
      Iranian traditional texts, "Gholaa" was the corrosive diseases on the surface and
      inner layer of mouth and tongue and divided into three types of bloody,
      phlegmatic and burned black bile types. Recurrent Aphthous Stomatitis (RAS) is
      equal to the black bile and phlegmatic types and minor aphthous type can be
      matched with phlegmatic type. The corrosive propagated lesions can be herpetic
      aphthous. In modern medicine, M. communis essential oil and its decoction
      decreased the average time of pain relief and decreased the size of ulcers in
      patients with minor RAS without any adverse effects. The number of ulcers was not
      the subjects of any different clinical trials. All patients were satisfied with
      M. communis topical essential oil (5%), and 81% patients were satisfied with M.
      communis topical decoctions (5%). It appears the efficacy of M. communis is
      related to its analgesic, anti-inflammatory, antiseptic and wound healing
      effects. CONCLUSION: M. communis is effective in minor RAS as its traditional
      claims and confirming its efficacy in major and herpetiform RAS and comparing the
      efficacy of its decoction topical formulations or essential oil topical ones are
      required more and larger experimental and clinical investigations in future.

PMID- 27693774
TI  - Anti-cholinergic and Ca2+-antagonist mechanisms explain the pharmacological basis
      for folkloric use of Sisymbrium irio Linn. in gastrointestinal, airways and
      vascular system ailments.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Sisymbrium irio Linn has been used
      traditionally in different regions of Pakistan for the treatment of
      gastrointestinal, airways and vascular system ailments. To insight the
      pharmacological basis, in vitro study was conducted in order to validate its
      folkloric uses. MATERIAL AND METHODS: 70% aqueous-methanolic extract of seeds
      from S. irio (Si.MEs) was tested on isolated rabbit aorta, jejunum and trachea
      strip hanged in tissue bath having physiological solutions aerated with carbogen
      and their responses were measured and recorded via Power Lab. RESULTS: The Si.MEs
      exhibited the transient spasmogenic effect (0.01-1.0mg/mL) on spontaneous jejunum
      contractions, followed by the spasmolytic effect. The addition of atropine
      resulted in blocking in spasmogenic effect while the spasmolytic effect was
      originated, suggesting the presence of an antimuscarinic effect. Likewise
      verapamil, Si.MEs (0.03-5mg/mL) repressed the high concentration K+(80mM)-induced
      contraction and also drifted the Ca2+ concentration-response curves toward right
      (0.3-3.0mg/mL), possibly signifying the Ca2+ channel blockade. Furthermore,
      Si.MEs exhibited nonspecific relaxant effect on carbachol (1uM)- and high
      concentration K+(80mM)-induced tracheal contractions in a way comparable to
      dicyclomine, suggesting the coexistence of Ca2+-antagonistic and/or
      antimuscarinic properties. Additionally, Si.MEs also relaxed the
      phenylephrine(1uM)- and high concentration K+(80mM)-induced aortic contraction
      (0.01-3mg/mL), suggesting blockade of Ca2+ channel. Moreover, oral administration
      of Si.MEs, as high as 6g per kg, did not produce lethality among the treated
      groups of mice. CONCLUSIONS: Aqueous-methanolic extract of seeds from S. irio
      (Si.MEs) exhibited the bronchodilator and gut modulator (spasmogenic and
      spasmolytic) activities, probably through dual blockade of muscarinic receptors
      and Ca2+ channels, whereas, vasodilator effect may be due to Ca2+ channels
      blockade.

PMID- 27693776
TI  - The cycle of healing - dissociation and attachment during treatment of CSA
      survivors.
AB  - Childhood sexual abuse (CSA) is an extreme traumatic event associated with
      numerous long lasting difficulties and symptoms (e.g., Herman, 1992). These
      include, among other things, the impediment of basic interpersonal structures of
      attachment (Rumstein-McKean & Hunsley, 2001), as well as impairment of mental
      integration manifested in dissociation (Van Den Bosch et al., 2003).
      Theoretically, attachment insecurities and dissociation are closely linked, since
      dissociation is generated as a way to resolve the conflicted attachment demands
      faced by the abused child (e.g., Liotti, 1992). Nevertheless, the directionality
      of association between attachment insecurities and dissociation during treatment
      of adult CSA survivors remains largely uninvestigated. Filling this gap, the
      present prospective study assessed female adult survivors of CSA who were
      outpatients at four treatment centers in Denmark (n=407), at the start of
      treatment (T1), 6 months after starting treatment (T2) and 12 months after
      starting treatment (T3). Results indicated that both attachment insecurities and
      dissociation reduced over time during treatment. Elevated attachment insecurities
      were associated with elevated dissociation at each of the measurements. Moreover,
      there was a reciprocal association between attachment avoidance and dissociation
      during treatment. Low levels of attachment avoidance predicted a decline in
      dissociation and vice versa. Findings suggest that treatment creates a cycle of
      healing in which rehabilitation of attachment fosters reintegration, which in
      turn deepens the restoration of attachment.

PMID- 27693777
TI  - Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of
      toxicity and apoptosis on HepG2 cells.
AB  - Myclobutanil is a conazole class fungicide widely used as an agrichemical. It is
      approved for use on fruit, vegetables and seed commodities in the EU and
      elsewhere to control fungi such as Ascomycetes, Fungi Imperfecti and,
      Basidiomycetes. Its widespread use has raised the issue of possible health risks
      for agrarian communities and the general population, which can be exposed to
      residues present in food and drinking water. The toxicities identified include
      adverse effects on liver and kidney and on the development of male reproductive
      organs. Since the liver is the first-line organ in the defense against
      xenobiotics, toxic effects on hepatic metabolism cause degeneration, necrosis,
      and tissue hypertrophy. Therefore, we investigated myclobutanil's effects on the
      human liver cell line HepG2. We found that myclobutanil increases the amount of
      fatty acids in these hepatic cells, as evaluated with Oil Red O staining, and
      progressively reduces cell viability from 1ppm to 500ppm. Analysis of biomarkers
      such as Bcl-xL/Bak and Mcl-1/Bak confirmed activation of cell death pathways at
      low doses. Therefore, myclobutanil may play an important role in the pathogenesis
      and progression of chronic hepatocellular diseases in humans.

PMID- 27693779
TI  - Managing molar-incisor hypomineralization: A systematic review.
AB  - OBJECTIVES: We systematically reviewed treatment modalities for MIH-affected
      molars and incisors. DATA: Trials on humans with >=1 MIH molar/incisor reporting
      on various treatments were included. Two authors independently searched and
      extracted records. Sample-size-weighted annual failure rates were estimated where
      appropriate. The risk of bias was assessed using the Newcastle-Ottawa scale.
      SOURCES: Electronic databases (PubMed, Embase, Cochrane CENTRAL, Google Scholar)
      were screened, and hand searches and cross-referencing performed. STUDY
      SELECTION: Fourteen (mainly observational) studies were included. Ten trials (381
      participants) investigated MIH-molars, four (139) MIH-incisors. For molars,
      remineralization, restorative or extraction therapies had been assessed. For
      restorative approaches, mean (SD) annual failure rates were highest for fissure
      sealants (12[6]%) and glass-ionomer restorations (12[2]%), and lowest for
      indirect restorations (1[3]%), preformed metal crowns (1.3 [2.1]%) and composite
      restorations (4[3]%). Ony study assessed extraction of molars in young patients
      (median age 8.2 years), the majority of them without malocclusions, but third
      molars in development. Spontaneous alignment of second molars was more frequent
      in the maxilla (55%) than the mandible (47%). For incisors, desensitizing agents
      successfully managed hypersensitivity. Micro-abrasion and composite veneers
      improved aesthetics. CONCLUSIONS: Few, mainly moderate to high-risk-studies
      investigated treatment of MIH. Remineralization or sealants seem suitable for MIH
      molars with limited severity and/or hypersensitivity. For severe cases,
      restorations with composites or indirect restorations or preformed metal crowns
      seem suitable. Prior to tooth extraction as last resort factors like the presence
      of a general malocclusion, patients' age and the status of neighboring teeth
      should be considered. No recommendations can be given for MIH-incisors. CLINICAL
      SIGNIFICANCE: Dentists need to consider the specific condition of each tooth and
      the needs and expectations of patients when deciding how to manage MIH. Strong
      recommendations are not possible based on the current evidence.

PMID- 27693778
TI  - Dentist material selection for single-unit crowns: Findings from the National
      Dental Practice-Based Research Network.
AB  - OBJECTIVES: Dentists enrolled in the National Dental Practice-Based Research
      Network completed a study questionnaire about techniques and materials used for
      single-unit crowns and an enrollment questionnaire about dentist/practice
      characteristics. The objectives were to quantify dentists' material
      recommendations and test the hypothesis that dentist's and practice's
      characteristics are significantly associated with these recommendations. METHODS:
      Surveyed dentists responded to a contextual scenario asking what material they
      would use for a single-unit crown on an anterior and posterior tooth. Material
      choices included: full metal, porcelain-fused-to-metal (PFM), all-zirconia,
      layered zirconia, lithium disilicate, leucite-reinforced ceramic, or other.
      RESULTS: 1777 of 2132 eligible dentists responded (83%). The top 3 choices for
      anterior crowns were lithium disilicate (54%), layered zirconia (17%), and
      leucite-reinforced glass ceramic (13%). There were significant differences
      (p<0.05) by dentist's gender, race, years since graduation, practice type,
      region, practice busyness, hours worked/week, and location type. The top 3
      choices for posterior crowns were all-zirconia (32%), PFM (31%), and lithium
      disilicate (21%). There were significant differences (p<0.05) by dentist's
      gender, practice type, region, practice busyness, insurance coverage, hours
      worked/week, and location type. CONCLUSIONS: Network dentists use a broad range
      of materials for single-unit crowns for anterior and posterior teeth, adopting
      newer materials into their practices as they become available. Material choices
      are significantly associated with dentist's and practice's characteristics.
      CLINICAL SIGNIFICANCE: Decisions for crown material may be influenced by factors
      unrelated to tooth and patient variables. Dentists should be cognizant of this
      when developing an evidence-based approach to selecting crown material.

PMID- 27693780
TI  - Tooth wear and quality of life among adults in the United Kingdom.
AB  - OBJECTIVE: To explore the association between tooth wear and quality of life
      among adults in the United Kingdom, independently of sociodemographic factors and
      other common oral conditions. METHODS: We used data from 5654 dentate adults who
      participated in the 2009 Adult Dental Health Survey. Tooth wear was assessed
      during clinical examination and classified as none, mild, moderate and severe
      based on the worst affected tooth recorded. The numbers of teeth with mild,
      moderate and severe tooth wear were used as alternative measures. Oral impacts on
      quality of life were measured using the short form of the Oral Health Impact
      Profile (OHIP-14). The associations between tooth wear measures and OHIP-14 total
      and domain scores were tested in negative binomial regression models adjusting
      for sociodemographic and clinical factors. RESULTS: Overall, 62% of participants
      had mild, 13% moderate and 2% severe tooth wear. Adults with severe tooth wear
      had a crude OHIP-14 total score higher than those without tooth wear (Rate Ratio:
      1.90; 95% Confidence Interval: 1.32-2.75). This association was attenuated after
      adjustment for confounders, particularly for other oral conditions (1.25; 95% CI:
      0.90-1.73). Moreover, adults with severe tooth wear reported higher OHIP-14
      domain scores in psychological discomfort (1.15; 95% CI: 1.06-1.25) and
      psychological disability (1.18; 95% CI: 1.10-1.30) than those without such
      condition. There was also evidence of a dose-response relationship; with higher
      OHIP-14 domain scores according to the number of teeth with severe tooth wear.
      CONCLUSION: This nationwide study among UK adults shows that severe tooth wear
      was negatively associated with psychological impacts on people's life. CLINICAL
      SIGNIFICANCE: Dentist should consider not only the patients' clinical
      characteristics, but also their impacts on quality of life and provide preventive
      or restorative management accordingly.

PMID- 27693781
TI  - Inorganic polyphosphate triggers upregulation of interleukin 11 in human
      osteoblast-like SaOS-2 cells.
AB  - Polyphosphate (polyP) is abundant in bone but its roles in signaling and control
      of gene expression remain unclear. Here, we investigate the effect of
      extracellular polyP on proliferation, migration, apoptosis, gene and protein
      expression in human osteoblast-like SaOS-2 cells. Extracellular polyP promoted
      SaOS-2 cell proliferation, increased rates of migration, inhibited apoptosis and
      stimulated the rapid phosphorylation of extracellular-signal-regulated kinase
      (ERK) directly through basic fibroblast growth factor receptor (bFGFR). cDNA
      microarray revealed that polyP induced significant upregulation of interleukin 11
      (IL-11) at both RNA and protein levels.

PMID- 27693782
TI  - Differentially transcriptional regulation on cell cycle pathway by silver
      nanoparticles from ionic silver in larval zebrafish (Danio rerio).
AB  - Silver nanoparticles (AgNPs) have a strong antibacterial activity and the
      relevant modes of actions have regarded as direct or indirect causes of toxicity
      observed in the environment. In this study, the transcriptomic profiles in larval
      zebrafish (Danio rerio) exposed to AgNPs (about 50 nm in size) and AgNO3 as a
      comparative ionic silver were investigated and analyzed using differential
      expressed gene (DEG), Gene ontology (GO) and Kyoto encyclopedia of genes and
      genomes (KEGG) pathway analyses. Results indicated that underlying molecular
      mechanisms are different each other. Interestingly, the global gene expression
      profiling showed that cell cycle pathway is affected by both AgNPs and dissolved
      Ag+, however its regulation pattern was opposite each other. To the best of our
      knowledge, the up-regulation of cell cycle pathway by AgNPs and down-regulation
      by Ag+ is the first reporting and suggests the distinguished toxicological
      perspective from a well-known hypothesis that Ag+ mainly regulates the cell
      cycle. This study provides novel insights onto the genotoxicological mechanisms
      of AgNPs.

PMID- 27693784
TI  - Non-invasive stem cell tracking in hindlimb ischemia animal model using bio
      orthogonal copper-free click chemistry.
AB  - Labeling of stem cells aims to distinguish transplanted cells from host cells,
      understand in vivo fate of transplanted cells, particularly important in stem
      cell therapy. Adipose-derived mesenchymal stem cells (ASCs) are considered as an
      emerging therapeutic option for tissue regeneration, but much remains to be
      understood regarding the in vivo evidence. In this study, a simple and efficient
      cell labeling method for labeling and tracking of stem cells was developed based
      on bio-orthogonal copper-free click chemistry, and it was applied in a mouse
      hindlimb ischemia model. The human ASCs were treated with tetra-acetylated N
      azidoacetyl-d-mannosamine (Ac4ManNAz) to generate glycoprotein with unnatural
      azide groups on the cell surface, and the generated azide groups were
      fluorescently labeled by specific binding of dibenzylcyclooctyne-conjugated Cy5
      (DBCO-Cy5). The safe and long-term labeling of the hASCs by this method was first
      investigated in vitro. Then the DBCO-Cy5-hASCs were transplanted into the
      hindlimb ischemia mice model, and we could monitor and track in vivo fate of the
      cells using optical imaging system. We could clearly observe the migration potent
      of the hASCs toward the ischemic lesion. This approach to design and tailor new
      method for labeling of stem cells may be useful to provide better understanding
      on the therapeutic effects of transplanted stem cells into the target diseases.

PMID- 27693785
TI  - The decreased N6-methyladenine DNA modification in cancer cells.
AB  - N6-methyladenine (6 mA) is a recently characterized DNA modification in mammalian
      genomes, although its biological importance remains to be resolved. Using a
      highly sensitive HPLC/MS/MS approach, here we report regulation of 6 mA
      modification in mammalian cells. To these aspects, down-regulation of 6 mA
      modification was first characterized in human cancer cells and tissues, relative
      to their normal controls. In contrast to the relative stable 5 mC modification, a
      dramatic decrease of 6 mA modification was found, showing that 6 mA is the most
      regulated DNA modification in cancers. In addition to the regulation in cancer
      cells, a hundreds-fold increase of 6 mA modification was found for in vitro
      cultured human cells, relative to the in vivo cells. This up-regulation was also
      confirmed with in vitro cultured mouse cells. Taken together, our study revealed
      distinct 6 mA modification profiles in the cancer and cultured cells. Considering
      its distinct regulation from that of 5 mC, our study suggests that 6 mA DNA
      modification may play a crucial role in cell fate transition of mammalian cells.

PMID- 27693783
TI  - The SH3 domain distinguishes the role of I-BAR proteins IRTKS and MIM in
      chemotactic response to serum.
AB  - The family of inverse BAR (I-BAR) domain proteins participates in a range of
      cellular processes associated with membrane dynamics and consists of five
      distinct members. Three of the I-BAR proteins, including insulin receptor
      tyrosine kinase substrate (IRTKS), contain an SH3 domain near their C-termini.
      Yet, the function of the SH3 domain of IRTKS remains uncharacterized. Here we
      report that in contrast to MIM, which is a prototype of I-BAR proteins and does
      not contain an SH3 domain, IRTKS promoted serum-induced cell migration along with
      enhanced phosphorylation of mitogen activated kinases Erk1/2 and p38, and
      activation of small GTPases Rac1 and Cdc42. In addition, cells overexpressing
      IRTKS exhibited an increased polarity characterized by elongated cytoplasm and
      extensive lamellipodia at leading edges. However, a mutant with deletion of the
      SH3 domain attenuated both cellular motility and p38 phosphorylation but had
      little effect on Erk1/2 phosphorylation. Also, a chimeric mutant in which the N
      terminal portion of MIM is fused with the C-terminal IRTKS, including the SH3
      domain, was able to promote chemotactic response to serum and cellular polarity.
      In contrast, a chimeric mutant in which the N-terminal IRTKS is fused with the C
      terminal MIM failed to do so. Furthermore, treatment of cells with SB203580, a
      selective inhibitor of p38, also neutralized the effect of IRTKS on cell
      migration. These data indicate that the SH3 domain distinguishes the function of
      IRTKS in promoting cell migration and inducing signal transduction from those of
      SH3-less I-BAR proteins.

PMID- 27693786
TI  - Melittin ameliorates CVB3-induced myocarditis via activation of the HDAC2
      mediated GSK-3beta/Nrf2/ARE signaling pathway.
AB  - Viral myocarditis (VMC) is characterized as an inflammatory process of the
      myocardium and can be fatal in infants and children. Melittin is a major
      polypeptide in honey bee venom that has been traditionally used against
      inflammation. However, its effect on VMC and the underlying molecular mechanism
      has not been reported. In this study, BALB/c mice were intraperitoneally injected
      with CVB3 to build a VMC model and treated with melittin. The results showed that
      melittin increased the mice's body weight and inhibited CVB3 replication. HE
      staining also showed that melittin alleviated myocardial injury in the VMC model.
      Flow cytometry showed that melittin inhibited myocardial cell apoptosis; in
      addition, real-time PCR showed that melittin decreased the expression of bax and
      caspase-3, and increased the expression of bcl-2. The results of
      echocardiographic examination showed that melittin improved cardiac function.
      Moreover, melittin decreased the activity of AST, CK, HBDH and LDH, and decreased
      the production of IL-1beta, IL-6, TNF-alpha and MCP-1 in CVB3-induced myocardial
      tissues. Finally, we also found that melittin increased the expression of HDAC2
      and activated the GSK-3beta/Nrf2/ARE signaling pathway, whereas these changes
      were reversed by inhibition of HDAC2 in VMC model mice. In conclusion, our
      results suggested that melittin ameliorates CVB3-induced myocarditis via
      activation of the HDAC2-mediated GSK-3beta/Nrf2/ARE signaling pathway.

PMID- 27693787
TI  - Lin28a protects against postinfarction myocardial remodeling and dysfunction
      through Sirt1 activation and autophagy enhancement.
AB  - BACKGROUND: Myocardial remodeling and cardiac dysfunction prevention may
      represent a therapeutic approach to reduce mortality in patients with myocardial
      infarction (MI). We investigated the effects of Lin28a in experimental MI models,
      as well as the mechanisms underlying these effects. METHODS: Left anterior
      descending (LAD) coronary artery ligation was used to construct an MI-induced
      injury model. Neonatal cardiomyocytes were isolated and cultured to investigate
      the mechanisms underlying the protective effects of Lin28a against MI-induced
      injury. RESULTS: Lin28a significantly inhibited left ventricular remodeling and
      cardiac dysfunction after MI, as demonstrated via echocardiography and
      hemodynamic measurements. Lin28a reduced cardiac enzyme and inflammatory marker
      release in mice subjected to MI-induced injury. The mechanisms underlying the
      protective effects of Lin28a against MI-induced injury were associated with
      autophagy enhancements and apoptosis inhibition. Consistent with these findings,
      Lin28a knockdown aggravated cardiac remodeling and dysfunction after MI-induced
      injury. Lin28a knockdown also inhibited cardiomyocyte autophagy and increased
      cardiomyocyte apoptosis in mice subjected to MI-induced injury. Interestingly,
      Sirt1 knockdown abolished the protective effects of Lin28a against cardiac
      remodeling and dysfunction after MI, and Lin28a failed to increase the numbers of
      GFP-LC3-positive punctae and decrease aggresome and p62 accumulation in Sirt1
      knockdown neonatal cardiomyocytes subjected to hypoxia-induced injury.
      CONCLUSIONS: Lin28a inhibits cardiac remodeling, improves cardiac function, and
      reduces cardiac enzyme and inflammatory marker release after MI. Lin28a also up
      regulates cardiomyocyte autophagy and inhibits cardiomyocyte apoptosis through
      Sirt1 activation.

PMID- 27693788
TI  - Enforced expression of hsa-miR-125a-3p in breast cancer cells potentiates
      docetaxel sensitivity via modulation of BRCA1 signaling.
AB  - Epigenetic gene inactivation by microRNAs (miRNAs) plays a key role in malignant
      transformation, prevention of apoptosis, drug resistance and metastasis. It has
      been shown that miR-125a is down-regulated in HER2-amplified and HER2
      overexpressing breast cancers (BCa), and this miRNA is believed to serve as an
      important tumor suppressor. miR-125a has two mature forms: hsa-miR-125a-3p and
      hsa-miR-125a-5p. However, the functional details of these miRNAs in BCa,
      particularly during pathogenesis of drug resistance, remain largely unexplored.
      Herein, we reported that hsa-miR-125a-3p expression was significantly reduced in
      chemoresistant BCa tissues and in experimentally established chemoresistant BCa
      cells. hsa-miR-125a-3p knockdown promoted cell proliferation and compromised
      docetaxel (Dox)-induced cell death, whereas overexpression of hsa-miR-125a-3p
      attenuated Dox chemoresistance in BCa cells. From a mechanistic standpoint, hsa
      miR-125a-3p directly targeted 3'-untranslated regions (3'-UTRs) of breast cancer
      early onset gene 1 (BRCA1) and inhibits its protein expression via translational
      repression mechanism. In addition, suppression of BRCA1 expression by siRNA
      treatment effectively improved hsa-miR-125a-3p deficiency-triggered
      chemoresistance in BCa cells. Collectively, these findings suggest that hsa-miR
      125a-3p may function as a tumor suppressor by regulating the BRCA1 signaling, and
      reintroduction of hsa-miR-125a-3p analogs could be a potential adjunct therapy
      for advanced/chemoresistant BCa.

PMID- 27693789
TI  - Plasma acylcarnitines during insulin stimulation in humans are reflective of age
      related metabolic dysfunction.
AB  - The purpose of this study was to determine if plasma acylcarnitine (AC) profiling
      is altered under hyperinsulinemic conditions as part of the aging process.
      Fifteen young, lean (19-29 years) and fifteen middle-to older-aged (57-82 years)
      individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples
      were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species
      and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin
      stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation. Insulin
      infusion decreased the majority of plasma short-, medium-, and long-chain (SC,
      MC, and LC, respectively) AC. However, during the initial 50 min, a number of MC
      and LC AC species (C10, C10:1, C12:1, C14, C16, C16:1, C18) remained elevated in
      aged individuals compared to their younger counterparts indicating a lag in
      responsiveness. Additionally, the insulin-induced decline in skeletal muscle ACC
      phosphorylation was blunted in the aged compared to young individuals (-24% vs. 
      56%, P < 0.05). These data suggest that a desensitization to insulin during
      aging, possibly at the level of skeletal muscle ACC phosphorylation, results in a
      diminished ability to transition to glucose oxidation indicative of metabolic
      inflexibility.

PMID- 27693790
TI  - EphA7 modulates apical constriction of hindbrain neuroepithelium during
      neurulation in Xenopus.
AB  - Eph receptor tyrosine kinases (RTKs) and their ephrin ligands play multiple roles
      in the developing nervous system, including cell segregation, axon guidance and
      synaptic plasticity. Here we report the expression and function of EphA7 in
      Xenopus hindbrain development. EphA7 is specifically expressed in the hindbrain
      throughout neurulation in Xenopus embryos. Knockdown of EphA7 by specific
      morpholino oligonucleotide (MO) disrupted cranial neural tube closure and
      disturbed apical constriction of hindbrain neuroepithelial cells, indicating
      weakened cell surface tension. In neural plate explants, EphA7 knockdown
      inhibited apical filamentous actin (F-actin) accumulation. We further showed that
      EphA7 is involved in the phosphorylation and activation of focal adhesion kinase
      (FAK) in vivo and in vitro, a key regulator of actin assembly. Our findings
      reveal that EphA7 functions as a critical regulator of apical constriction of
      hindbrain neuroepithelial cells.

PMID- 27693791
TI  - Sodium fluoride as a nucleating factor for Mg-actin polymerization.
AB  - Dynamic instability of actin filaments can be inhibited by Pi analogs beryllium
      fluoride and aluminium fluoride that mimic the intermediate ADP-Pi state and
      stabilize actin filaments. On the other hand, the phosphoryl transfer enzymes can
      be activated in the absence of aluminium by magnesium fluoride if magnesium ions
      and sodium fluoride (NaF) were present in the solution. Whether magnesium
      fluoride promotes functional activities of actin is not known. Here we show, for
      the first time, that sodium fluoride strongly accelerates polymerization of
      highly dynamic Mg-F-actin assembled from the monomers proteolytically cleaved
      between Gly42 and Val43 within the D-loop with actin-specific protease
      protealysin (Pln-actin), apparently due to stabilization of nuclei formed at the
      initial step of actin polymerization. Thereby, NaF did not inhibit the ATPase
      activity (subunit exchange) on Pln-F-actin, did not increase the amount of Pln-F
      actin sedimented by ultracentrifugation, and did not stabilize the inter-strand
      contacts of Pln-F-actin. On the other hand, NaF diminished accessibility of the
      nucleotide binding cleft of Mg-G-actin to trypsin, pointing to an additional
      cleft closure, and additionally protected the D-loop from the protealysin
      cleavage in Mg-F-actin, thus indicating that the longitudinal contacts are
      stabilized. We also demonstrate that in cultured cells NaF can directly promote
      assembly of F-actin structures under conditions when the corresponding activity
      of the RhoA pathway is inhibited. These data suggest that the NaF-induced
      assembly of actin filaments is promoted by magnesium fluoride that can be formed
      by the NaF-originating fluoride and the actin tightly bound magnesium.

PMID- 27693792
TI  - Serum starvation induces anti-apoptotic cIAP1 to promote mitophagy through
      ubiquitination.
AB  - Mitophagy is a highly specialised type of autophagy that plays an important role
      in regulating mitochondrial dynamics and controls cellular quality during stress.
      In this study, we established that serum starvation led to induction of cellular
      inhibitor of apoptosis protein-1 (cIAP1), which regulates mitophagy through
      ubiquitination. Importantly, gain and loss of function of cIAP1 resulted in
      concomitant alteration in mitophagy confirming the direct implication of cIAP1 in
      induction of mitophagy. Interestingly, it was observed that cIAP1 translocated to
      mitochondria to associate with TOM20, Ulk1, and LC3 to initiate mitophagy.
      Further, cIAP1-induced mitophagy led to dysfunctional mitochondria that resulted
      in abrogation of mitochondrial oxygen consumption rate along with the decrease in
      ATP levels. The ubiquitination of cIAP1 was found to be the critical regulator of
      mitophagy. The disruption of cIAP1-ubiquitin interaction by PYR41 ensured the
      abrogation of cIAP1-LC3 interaction and mitophagy inhibition. Our study revealed
      an important function of cIAP1 as a crucial molecular link between autophagy and
      apoptosis for regulation of mitochondrial dynamics to mitigate cellular stress.

PMID- 27693793
TI  - Buckling of microtubules on elastic media via breakable bonds.
AB  - Buckling of microtubules observed in cells has been reconstructed on a two
      dimensional elastic medium consisting of kinesins grafted over compressible
      substrates, enabling precise control of experimental conditions and quantitative
      analysis. However, interpretations of the observations have ambiguities due to
      inevitable experimental difficulties. In this study, with computer simulations,
      we investigated importance of the mode of interaction of microtubule with elastic
      medium in the buckling behavior of microtubule. By taking into consideration of
      forced-induced detachments of kinesins from microtubules, our simulations
      reproduced the previous experimental results, and showed deviations from
      predictions of the elastic foundation model. On the other hand, with hypothetical
      linkers permanently bound to microtubules, our simulation reproduced the
      predictions of the elastic foundation model. By analyzing the results of the
      simulations, we investigated as to why the difference arose. These findings
      indicate the importance of the mode of interaction of microtubule with the medium
      in the buckling behavior of microtubule. Our findings would bring new insights on
      buckling of microtubules in living cells.

PMID- 27693794
TI  - Dietary gamma oryzanol plays a significant role in the anti-inflammatory activity
      of rice bran oil by decreasing pro-inflammatory mediators secreted by peritoneal
      macrophages of rats.
AB  - Ricebran oil (RBO) is promoted as heart friendly oil because of its ability to
      maintain serum lipids at desirable levels. Inflammation also plays an important
      role on cardiovascular health. The role of minor constituents present in
      unsaponifiable fraction (UF) of RBO on inflammatory markers is not well
      understood. To evaluate this, we have taken RBO with UF (RBO-N), RBO stripped of
      UF (RBO-MCR) and RBO-MCR supplemented with UF from RBO (UFRBO) or Gamma-Oryzanol
      (gamma-ORY) were added in AIN-93 diets which was then fed to Wistar rats for a
      period of 60 days. Groundnut oil with UF (GNO-N), UF removed GNO (GNO-MCR) and
      GNO-MCR supplemented with UF from RBO or gamma-ORY was also used for comparison.
      The peritoneal macrophages from the rats were activated and pro-inflammatory
      mediators such as Reactive Oxygen Species (ROS), eicosanoids, cytokines,
      hydrolytic enzymes of lysosomal origin were monitored. The results indicated that
      UF of RBO and gamma-ORY supplemented in the dietary oils play a significant role
      in reducing the secretion of pro-inflammatory mediators by macrophages. Hence
      gamma-ORY in RBO significantly contributed to the anti-inflammatory properties of
      RBO.

PMID- 27693795
TI  - Local administration of a hedgehog agonist accelerates fracture healing in a
      mouse model.
AB  - Bone fracture healing is processed through multiple biological stages including
      the transition from cartilaginous callus to bony callus formation. Because of its
      specific, temporal and indispensable functions demonstrated by mouse genetic
      studies, Hedgehog (Hh) signaling is one of the most potent signaling pathways
      involved in these processes, but the effect of Hh-signaling activation by small
      compounds on the repair process had not yet been addressed. Here we examined
      therapeutic effects of local and one shot-administration of the Hh agonist known
      as smoothened agonist (SAG) on bone fracture healing in a mouse model. A
      quantitative analysis with three-dimensional micro-computed tomography showed
      that SAG administration increased the size of both the cartilaginous callus and
      bony callus at 14 days after the surgery. A histological analysis showed that SAG
      administration increased the number of cells expressing a proliferation marker
      and a chondrocyte marker in cartilaginous callus as well as the cells expressing
      an osteoblast marker in bony callus. These results indicate that the SAG
      administration resulted in an enhancement of callus formation during bone
      fracture healing, which is at least in part mediated by an increase in
      chondrocyte proliferation in cartilaginous callus and the promotion of bone
      formation in bony callus. Therapeutic strategies with a SAG-mediated protocol may
      thus be useful for the treatment of bone fractures.

PMID- 27693796
TI  - Automated individual-level parcellation of Broca's region based on functional
      connectivity.
AB  - Broca's region can be subdivided into its constituent areas 44 and 45 based on
      established differences in connectivity to superior temporal and inferior
      parietal regions. The current study builds on our previous work manually
      parcellating Broca's area on the individual-level by applying these anatomical
      criteria to functional connectivity data. Here we present an automated observer
      independent and anatomy-informed parcellation pipeline with comparable precision
      to the manual labels at the individual-level. The method first extracts
      individualized connectivity templates of areas 44 and 45 by assigning to each
      surface vertex within the ventrolateral frontal cortex the partial correlation
      value of its functional connectivity to group-level templates of areas 44 and 45,
      accounting for other template connectivity patterns. To account for cross-subject
      variability in connectivity, the partial correlation procedure is then repeated
      using individual-level network templates, including individual-level connectivity
      from areas 44 and 45. Each node is finally labeled as area 44, 45, or neither,
      using a winner-take-all approach. The method also incorporates prior knowledge of
      anatomical location by weighting the results using spatial probability maps. The
      resulting area labels show a high degree of spatial overlap with the gold
      standard manual labels, and group-average area maps are consistent with
      cytoarchitectonic probability maps of areas 44 and 45. To facilitate
      reproducibility and to demonstrate that the method can be applied to resting
      state fMRI datasets with varying acquisition and preprocessing parameters, the
      labeling procedure is applied to two open-source datasets from the Human
      Connectome Project and the Nathan Kline Institute Rockland Sample. While the
      current study focuses on Broca's region, the method is adaptable to parcellate
      other cortical regions with distinct connectivity profiles.

PMID- 27693797
TI  - The role of histamine H1, H2 and H3 receptors of ventral posteromedial nucleus of
      thalamus in modulation of trigeminal pain.
AB  - Histamine receptors are involved in supraspinal modulation of pain. In the
      present study, we investigated the effects of microinjection of histamine H1, H2
      and H3 receptor antagonists and agonists into the ventral posteromedial (VPM)
      nucleus of the thalamus on two models of trigeminal pain. Right and left sides of
      VPM were implanted with two guide cannulas. Corneal pain was induced by local
      corneal surface application of hypertonic saline and the number of eye wipes was
      recorded. The duration of face rubbing, as an orofacial pain measure, was
      recorded after subcutaneous (s.c.) injection of capsaicin into the vibrissa pad.
      2-pyridylethylamine (2-PEA, a histamine H1 receptor agonist, 4ug/site) and
      dimaprit (a histamine H2 receptor agonist, 1 and 4ug/site) suppressed corneal and
      orofacial pains. Mepyramine (a histamine H1 receptor antagonist) and ranitidine
      (a histamine H2 receptor antagonist) at the similar doses of 0.5, 2 and 8ug/site
      alone had no effects on trigeminal pain. Prior microinjection of mepyramine and
      ranitidine at a similar dose of 8ug/site inhibited the antinociceptive effects of
      2-PEA (4ug/site) and dimaprit (4ug/site), respectively. Immepip (a histamine H3
      receptor agonist, 1 and 4ug/site) increased, and thioperamide (a histamine H3
      receptor antagonist, 2 and 8ug/site) attenuated nociceptive responses. Prior
      microinjection of thioperamide (8ug/site) prevented immepip (4ug/site)-induced
      nociception. These chemicals did not change locomotor behavior. It is concluded
      that post-synaptic histamine H2, and to a lesser extent H1, receptors and pre
      synaptic histamine H3 receptor may be involved in VPM modulation of trigeminal
      pain.

PMID- 27693798
TI  - Chronic LPSF/GQ-02 treatment attenuates inflammation and atherosclerosis
      development in LDLr-/- mice.
AB  - BACKGROUND: Atherosclerosis is a complex disorder with a multifactorial
      pathogenesis. We previously indicated that the new TZD LPSF/GQ-02 inhibits
      hepatic steatosis and inflammation, which are reported as risk factors for
      atherosclerosis development. Here, we explored the effects of LPSF/GQ-02 on
      atherosclerosis in LDLr-/- mice comparing two treatment periods. METHODS AND
      RESULTS: LDLr-/- mice were fed a high-fat diet for 10 and 12 weeks and received
      oral treatment with LPSF/GQ-02 (30mg/kg/day) or pioglitazone (20mg/kg/day) for 15
      and 30 days, respectively. Both treatment protocols with LPSF/GQ-02 resulted in
      lower collagen density in the atherosclerotic lesions. In addition, the treatment
      for 15 days also decreased mRNA levels of CD40, MCP-1, ABCG1 and upregulated
      PPARalpha, whereas the 30-days treatment reduced the protein levels of LOX-1, p
      IkappaBalpha and p-NFkappaB. CONCLUSION: This study provides evidence that
      LPSF/GQ-02 affects the composition and growth of atherosclerotic lesions in LDLr
      /- mice. Moreover, our data also support previous findings showing anti
      inflammatory properties of LPSF/GQ-02 and reinforce the therapeutic potential of
      this TZD for treating atherosclerosis and inflammation-related disorders.

PMID- 27693799
TI  - Tanshinone IIA inhibits myocardial remodeling induced by pressure overload via
      suppressing oxidative stress and inflammation: Possible role of silent
      information regulator 1.
AB  - Tanshinone IIA (Tan) exerts potential protective effects against cardiovascular
      diseases. Oxidative stress and inflammation are involved in cardiac hypertrophy.
      Activation of silent information regulator 1 (SIRT1) signaling has been suggested
      to attenuate cardiac hypertrophy. This study aims to evaluate the antioxidative
      and anti-inflammatory effects of Tan treatment in pressure overload-induced
      myocardial remodeling and elucidated its potential mechanisms. Sprague-Dawley
      rats were treated with Tan in the absence or presence of the SIRT1 inhibitor
      sirtinol (Snl) and then subjected to transverse aortic constriction (TAC). Tan
      conferred cardioprotective effects by improving cardiac function, reducing
      apoptosis and myocardial remodeling, upregulating SIRT1, Bcl-2 expressions, and
      downregulating Bax and caspase-3 expressions. Snl attenuated these effects by
      inhibiting SIRT1 signaling. Tan treatment also reduced myocardium malondialdehyde
      (MDA) content, and cardiac inflammatory cytokines (TNF-alpha and IL-6) and
      increased myocardium superoxide dismutase (SOD) level. However, these effects
      were also abolished by Snl. In conclusion, these results indicate that Tan
      significantly attenuates TAC-induced myocardial remodeling possibly due to its
      strong anti-oxidative and anti-inflammatory activity. Importantly, SIRT1
      signaling activation is involved in this process.

PMID- 27693800
TI  - Effects of ZD0947, a novel and potent ATP-sensitive K+ channel opener, on smooth
      muscle-type ATP-sensitive K+ channels.
AB  - The effects of ZD0947, a novel ATP-sensitive K+ channel (KATP channel) opener, on
      the activity of reconstituted KATP channels were investigated using cell-attached
      recordings. KATP channels were studied in HEK 293 cells by co-expression of
      inwardly rectifying-6 family K+ channel subunits (Kir6.x: Kir6.1 and Kir6.2) with
      3 different types of sulphonylurea receptors (SUR.x: SUR1, SUR2A and SUR2B).
      ZD0947 (100uM) activated SUR2B/Kir6.2 channels in a concentration-dependent
      manner, but caused only weak activation of SUR1/Kir6.2 channels and SUR2A/Kir6.2
      channels expressed in HEK 293 cells. ZD0947 reversibly suppressed diazoxide
      elicited SUR1/Kir6.2 channels activity and pinacidil-elicited SUR2A/Kir6.2
      channel activity. However, ZD0947 did not affect SUR2B/Kir6.2 channels fully
      activated by 100uM pinacidil. ZD0947 had little inhibitory effects on the
      activity of Kir6.2DeltaC26 channels (a truncated isoform of Kir6.2) or its mutant
      channels (i.e. Kir6.2DeltaC26C166A) expressed in HEK 293 cells. ZD0947 also
      elicited activity in SUR2B/Kir6.1 channels expressed in HEK 293 cells, in a
      concentration-dependent manner. Therefore, ZD0947 is a relatively effective
      activator of smooth muscle-type KATP channels (SUR2B/Kir6.1 and SUR2B/Kir6.2) but
      is a partial antagonist of pancreatic-type KATP channels (i.e. SUR1/Kir6.2) and
      cardiac-type KATP channels (i.e. SUR2A/Kir6.2). These results suggest that a
      pharmacological agent can possess either agonist or antagonist actions on the
      activity of KATP channels, depending on the subtype of SUR.x.

PMID- 27693801
TI  - The alpha2beta3gamma2 GABAA receptor preferring agonist NS11394 aggravates
      dystonia in the phenotypic dtsz model.
AB  - Dystonia is a movement disorder, characterized by involuntary muscle contractions
      resulting in abnormal movements and/or postures. Antidystonic effects of
      benzodiazepines in patients with different types of dystonia could be replicated
      in the dtsz mutant hamster, a phenotypic model of paroxysmal dystonia. Compounds
      with preferred binding at specific subunits of the gamma aminobutyric acid type A
      (GABAA) receptor may provide a more beneficial spectrum of effects in comparison
      with benzodiazepines. We therefore examined the effects of the alpha1beta3gamma2
      GABAA receptor preferring compound zolpidem (2.0-10.0mg/kg i.p.) and of the
      alpha2beta3gamma2 GABAA receptor preferring compound NS11394 (3.0-30mg/kg i.p.)
      on the severity of dystonia in the dtsz mutant in comparison with the
      benzodiazepine clonazepam (0.5-1.0mg/kg i.p.). As expected, clonazepam exerted
      pronounced antidystonic effects. While zolpidem showed moderate beneficial
      effects, NS11394 significantly increased the severity of dystonia. The present
      results indicate for the first time that positive GABAA receptor modulators show
      contrary effects on dystonia dependent on their preference for alpha-subunits.
      The potential link between alterations in GABAA receptor subunits and GABAergic
      disinhibition in dystonia deserves further attention in research on the
      pathophysiology and therapeutic targets.

PMID- 27693802
TI  - Efficacy of CoenzymeQ10 in inhibiting monosodium urate crystal-induced
      inflammation in rats.
AB  - Gout is a type of arthritis, which could result from the deposition of monosodium
      urate crystals in joints. It can cause redness, burning pain, inflammation of
      joints especially in big toe. In this study, we have looked for anti-arthritic
      effect of coenzyme Q10 (CoQ10) on monosodium urate crystal-induced inflammation
      in rats and compared it with that of the non-steroidal anti-inflammatory drug,
      indomethacin. The evaluation was done by measuring the paw volume, antioxidant
      status, lipid peroxidation, lysosomal enzymes (beta-glcuronidase, beta
      galactosidase, N-acetyl-beta-d-glucosaminidase, acid phosphatase) activities and
      histopathological studies. Paw volume, the levels of lysosomal enzymes, lipid
      peroxidation were significantly (P<0.05) increased and the antioxidant activity
      status was in turn decreased in monosodium urate crystal-induced rats. CoQ10
      (10mg/kg/b.w. orally) treated monosodium urate crystal-induced rats showed near
      normal activities of lysosomal enzymes, reduced levels of lipid peroxidation,
      near normal paw volume and antioxidant status. CoQ10 was also able to minimize
      mononuclear cell infiltration and damage to articular cartilage. Current study
      indicates that CoQ10 possesses anti-inflammatory effect against gouty arthritis
      and can be used to treat acute form of gouty arthritis.

PMID- 27693803
TI  - Determination of personal care products -benzophenones and parabens- in human
      menstrual blood.
AB  - Benzophenones and parabens are synthetic chemicals used in many personal care
      products, foods and pharmaceuticals. Benzophenones are used to protect the skin
      and materials from the adverse effects of UV-radiation, and parabens are used as
      preservatives. Despite their widespread occurrence and proven endocrine
      disrupting activity, relatively little is known about human exposure to these
      compounds. In the present work, an analytical method based on sample treatment
      using dispersive liquid-liquid microextraction (DLLME) for the extraction of six
      benzophenones (benzophenone-1, -2, -3, -6, -8 and 4-hydroxybenzophenone) and four
      parabens (methyl-, ethyl-, propyl- and butyl- paraben) from human menstrual blood
      samples, followed by ultrahigh performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS) analysis, is proposed and validated. The method was
      validated using matrix-matched standard calibration followed by a recovery assay
      with spiked samples. The limits of detection ranged from 0.1 to 0.3ngmL-1, with
      recoveries of 93.8% to 108.9%, and precision (evaluated as relative standard
      deviation) lower than 14% for all selected compounds. This method was
      successfully applied for the determination of the target compounds in 25 samples
      of human menstrual blood. Methylparaben and benzophenone-3 were the most
      frequently detected compounds (96%).

PMID- 27693804
TI  - Emergency management of severe hyperkalemia: Guideline for best practice and
      opportunities for the future.
AB  - Hyperkalemia is a common electrolyte disorder, especially in chronic kidney
      disease, diabetes mellitus, or heart failure. Hyperkalemia can lead to
      potentially fatal cardiac dysrhythmias, and it is associated with increased
      mortality. Determining whether emergency therapy is warranted is largely based on
      subjective clinical judgment. The Investigator Network Initiative Cardiovascular
      and Renal Clinical Trialists (INI-CRCT) aimed to evaluate the current knowledge
      pertaining to the emergency treatment of hyperkalemia. The INI-CRCT developed a
      treatment algorithm reflecting expert opinion of best practices in the context of
      current evidence, identified gaps in knowledge, and set priorities for future
      research. We searched PubMed (to August 4, 2015) for consensus guidelines,
      reviews, randomized clinical trials, and observational studies, limited to
      English language but not by publication date. Treatment approaches are based on
      small studies, anecdotal experience, and traditional practice patterns. The
      safety and real-world effectiveness of standard therapies remain unproven.
      Prospective research is needed and should include studies to better characterize
      the population, define the serum potassium thresholds where life-threatening
      arrhythmias are imminent, assess the potassium and electrocardiogram response to
      standard interventions. Randomized, controlled trials are needed to test the
      safety and efficacy of new potassium binders for the emergency treatment of
      severe hyperkalemia in hemodynamically stable patients. Existing emergency
      treatments for severe hyperkalemia are not supported by a compelling body of
      evidence, and they are used inconsistently across institutions, with potentially
      significant associated side effects. Further research is needed to fill knowledge
      gaps, and definitive clinical trials are needed to better define optimal
      management strategies, and ultimately to improve outcomes in these patients.

PMID- 27693807
TI  - An image-processing based technique to obtain instantaneous horizontal walking
      and running speed.
AB  - Walking and running speed is a fundamental parameter studied in a wide range of
      areas such as sport biomechanics, rehabilitation, health promotion of the
      elderly, etc. Given that walking or running speed is not constant even within a
      stride, instantaneous changes in the body motion need to be evaluated to better
      understand one's performance. In this study, a new cost- and time- efficient
      methodology to determine instantaneous horizontal walking and running speed was
      developed. The newly developed method processes the movies taken with a (high
      speed) camera. It consists of five sub-steps, which are performed in a serial
      order: (1) Subtraction of the background image, (2) filtering, (3) binarization
      and centroid determination, (4) transformation to the laboratory coordinate
      system and (5) differentiation. To test the accuracy of the newly developed
      method, the output (position and speed) was compared with the data obtained using
      motion capture. The average root mean squared (RMS) error (difference between the
      outputs of the newly developed method and motion capture) of position-time curves
      was 0.011m-0.033m. The average RMS error of speed-time curves was 0.054m/s
      0.076m/s. It was shown that this new method produces accurate outputs of
      instantaneous walking and running speed.

PMID- 27693806
TI  - Impaired postural control in children with developmental coordination disorder is
      related to less efficient central as well as peripheral control.
AB  - BACKGROUND: Developmental coordination disorder (DCD) is a neurodevelopmental
      impairment that affects approximately 6% of children in primary school age.
      Children with DCD are characterized by impaired postural control. It has yet to
      be determined what effect peripheral and central neuromuscular control has on
      their balance control. OBJECTIVE: The aim of this study was to investigate the
      underlying mechanisms to impaired postural control in children with DCD using the
      rambling-trembling decomposition of the center of pressure (CoP). METHOD: Nine
      children with DCD (9.0+/-0.5years, 7 boys, 2 girls) and 10 age- and gender
      matched typically developing children (TD) with normal motor proficiency (9.1+/
      0.4years, 7 boys and 3 girls) performed 3*30s bipedal standing on a force plate
      in six sensory conditions following the sensory organization procedure. Sway
      length was measured and rambling-trembling decomposition of CoP was calculated in
      medio-lateral (ML) and anterior-posterior (AP) direction. RESULTS: Both rambling
      and trembling were larger for the children with DCD in AP (p=0.031; p=0.050) and
      ML direction (p=0.025; p=0.007), respectively. ML rambling trajectories did not
      differ in any conditions with fixed support surface. In ML direction children
      with DCD had a lower relative contribution of rambling to total sway (p=0.013).
      CONCLUSION: This study showed that impaired postural control in children with DCD
      is associated with less efficient supraspinal control represented by increased
      rambling, but also by reduced spinal feedback control or peripheral control
      manifested as increased trembling.

PMID- 27693805
TI  - Role of dietary fatty acids in liver injury caused by vinyl chloride metabolites
      in mice.
AB  - BACKGROUND: Vinyl chloride (VC) causes toxicant-associated steatohepatitis at
      high exposure levels. Recent work by this group suggests that underlying liver
      disease may predispose the liver to VC hepatotoxicity at lower exposure levels.
      The most common form of underlying liver disease in the developed world is non
      alcoholic fatty liver disease (NAFLD). It is well-known that the type of dietary
      fat can play an important role in the pathogenesis of NAFLD. However, whether the
      combination of dietary fat and VC/metabolites promotes liver injury has not been
      studied. METHODS: Mice were administered chloroethanol (CE - a VC metabolite) or
      vehicle once, 10weeks after being fed diets rich in saturated fatty acids (HSFA),
      rich in poly-unsaturated fatty acids (HPUFA), or the respective low-fat control
      diets (LSFA; LPUFA). RESULTS: In control mice, chloroethanol caused no detectable
      liver injury, as determined by plasma transaminases and histologic indices of
      damage. In HSFA-fed mice, chloroethanol increased HSFA-induced liver damage,
      steatosis, infiltrating inflammatory cells, hepatic expression of proinflammatory
      cytokines, and markers of endoplasmic reticulum (ER) stress. Moreover, markers of
      inflammasome activation were increased, while markers of inflammasome inhibition
      were downregulated. In mice fed HPUFA all of these effects were significantly
      attenuated. CONCLUSIONS: Chloroethanol promotes inflammatory liver injury caused
      by dietary fatty acids. This effect is far more exacerbated with saturated fat,
      versus poly-unsaturated fat; and strongly correlates with a robust activation of
      the NLRP3 inflammasome in the saturated fed animals only. Taken together these
      data support the hypothesis that environmental toxicant exposure can exacerbate
      the severity of NAFLD/NASH.

PMID- 27693808
TI  - Intravenous lacosamide in seizure emergencies: Observations from a hospitalized
      in-patient adult population.
AB  - PURPOSE: to evaluate the efficacy and safety of intravenous (IV) lacosamide (LCM)
      in the treatment of seizure clusters (SC) and status epilepticus (SE) in
      hospitalized adult patients. METHODS: we prospectively analyzed treatment
      response, seizure outcome, and adverse effects of IV LCM in 38 patients with
      seizure emergencies (15 with SC, 23 with SE) during a hospital stay. The loading
      dose of IV LCM was 200-400mg and the maintenance dose was 200-400mg daily.
      Response to IV LCM was evaluated within 20min, 4h and 24h of LCM infusion.
      RESULTS: an acute anti-seizure effect after IV LCM was especially evident when it
      was first used - (SC) or second line (established SE) treatment. In particular,
      87% of SC patients (13/15) and 80% of established SE (8/10) demonstrated response
      to LCM treatment, while no patients with super-refractory SE (0/8) responded to
      IV LCM according to our criteria. The loading of IV LCM was well tolerated, with
      mild adverse effects (2/38 temporary dizziness). In most patients, during and
      after administration of the loading dose of IV LCM a temporary (30min-1h)
      sedation was observed. No ECG and laboratory values-changes were documented in
      any of the patients. CONCLUSIONS: LCM is an effective and well-tolerated
      treatment when used to treat SC in hospitalized adult patients. As add-on
      therapy, it may be useful to stop seizure activity in patients with focal SE not
      responding to first/second-line intravenous AEDs.

PMID- 27693809
TI  - Ultrastructural Investigation of Pelvic Peritoneum in Patients With Chronic
      Pelvic Pain and Subtle Endometriosis in Association With Chromoendoscopy.
AB  - STUDY OBJECTIVE: To evaluate the pelvic peritoneum under chromoendoscopy by
      scanning electron microscopy (SEM) as well as light microscopy with hematoxylin
      and eosin staining and immunohistochemistry (IHC) assays in patients with chronic
      pelvic pain (CPP) associated with subtle endometriosis. DESIGN: Case series study
      (Canadian Task Force classification II). SETTING: A referral academic community
      tertiary medical center. PATIENTS: Three women aged 29 to 37 years were referred
      to the obstetrics and gynecology clinic of the tertiary university hospital with
      CPP. They were suspicious for endometriosis, were not responding to medical
      treatments, and had undergone previous pelvic laparoscopy to determine the stage
      of endometriosis and preparation of peritoneal samples under the guidance of
      staining with methylene blue in 0.25% dilution. INTERVENTIONS: Comparison of
      stained and unstained pelvic peritoneal samples after the instillation of 0.25%
      methylene blue into the pelvic cavity. MEASUREMENTS AND MAIN RESULTS: In 3
      patients, laparoscopic examination showed minimal endometriosis. A total of 18
      samples (9 stained and 9 unstained) from the 3 patients were prepared for SEM.
      Ten of the samples (55.6%) showed microstructural peritoneal destruction (7 of 9
      stained [77.7%] and 3 of 9 [33.4%] unstained). Eighteen samples (9 stained and 9
      unstained) from the 3 patients were also prepared for IHC. Six of these samples
      (33.3%) were S-100-positive, including 4 of 9 (44.4%) stained samples and 2 of 9
      (22.2%) unstained samples. CONCLUSIONS: In general, in the context of CPP and
      endometriosis, there is no established relationship between the severity of pain
      and stage of endometriosis. In the pathophysiology of CPP associated with
      endometriosis, ultrastructural changes can play a significant role. Under
      methylene blue staining, some destroyed areas were detected, but the stained
      areas do not necessarily correlate with increased microstructural peritoneal
      destruction.

PMID- 27693810
TI  - First Case of ROLL Technique for Mesorectal Recurrence Excision.
AB  - The radio-guided occult lesion localization (ROLL) technique has been in use
      since the mid-1990s, mainly in breast surgery. Today, ROLL is used for numerous
      oncologic pathologies, including parathyroid lesions, melanomas, and colorectal
      tumors. We report a patient with an 11-mm left mesorectal solitary recurrence of
      a primary ovarian cancer in whom the ROLL technique was used to identify the
      implant. A radioisotope was introduced through a 22-gauge needle with endoscopic
      ultrasound technique using an linear echo endoscope. On the day of surgery, the
      patient's perianal region was scanned with a gamma probe to identify the area of
      maximal radioactivity, to determine the optimal placement of the incision over
      the lesion. After macroscopic excision of the lesion, radioactivity was measured
      in the lesion bed to ensure complete removal of affected tissues. In our case,
      the ROLL technique was performed safely for the detection and excision of a
      recurrent lesion of difficult identification. To our knowledge, this is the first
      reported case involving use of the ROLL technique to aid the excision of a
      mesorectal lesion.

PMID- 27693811
TI  - Book lung development in embryos of the cobweb spider, Parasteatoda tepidariorum
      C. L. Koch, 1841 (Araneomorphae, Theridiidae).
AB  - Light and transmission electron microscopy were used to study the development of
      book lungs in embryos of the spider Parasteatoda tepidariorum. There is a
      bilateral cluster of temporary lamellae that form just posterior to the second
      opisthosomal (O2) limb buds. These lamellae are replaced by advanced embryo (AE)
      book lungs that continue into postembryonic stages. Results herein agree with
      earlier suggestions that the O2 limb buds become the AE book lungs. Each O2 limb
      bud merges with the ventral surface of the O2 segment, where the limb bud/book
      lung is internalized by covering with epidermis. A strand of tissue
      (entapophysis) from the epidermis at the posterior opisthosoma provides precursor
      cells for the book lung lamellae, and possibly entapophysis cells induce limb bud
      cells to align and produce lamellae. Electron micrographs show the different
      modes (I-III) of lumen formation. The result is a spiracle, atrium and
      alternating air and hemolymph channels. A hypothesis is presented for the role of
      precursor cell polarity in producing the planar tissue polarity of the channels.
      Some type of apical/apical affinity results in air channels, while basal/basal
      affinity results in hemolymph channels. Strong basal/basal affinity is likely as
      opposed cells in hemolymph channels extend basal processes that span the channel
      and start pillar trabeculae that continue in postembryonic stages.

PMID- 27693812
TI  - Lifestyle factors and prostate-specific antigen (PSA) testing in UK Biobank:
      Implications for epidemiological research.
AB  - BACKGROUND: The central role of prostate-specific antigen (PSA) testing in the
      diagnosis of prostate cancer leads to the possibility that observational studies
      that report associations between risk factors and prostate cancer could be
      affected by detection bias. This study aims to investigate whether reported risk
      factors for prostate cancer are associated with PSA testing in a large middle
      aged population-based cohort in the UK. METHODS: The cross-sectional association
      between a wide range of sociodemographic, lifestyle, dietary and health
      characteristics with PSA testing was examined in 212,039 men aged 40-69 years in
      UK Biobank. RESULTS: A total of 62,022 (29%) men reported they had ever had a PSA
      test. A wide range of factors was associated with a higher likelihood of PSA
      testing including age, height, education level, family history of prostate
      cancer, black ethnic origin, not being in paid/self-employment, living with a
      wife or partner, having had a vasectomy, being diagnosed with cancer or
      hypertension and having a high dietary intake of cereal, cooked and salad/raw
      vegetables, fresh fruit and tea. Conversely, socioeconomic deprivation, Asian
      ethnic origin, current smoking, low alcohol intake, high body-mass index, high
      coffee consumption and being diagnosed with diabetes, heart disease or stroke
      were associated with a lower likelihood of PSA testing. CONCLUSIONS: A variety of
      sociodemographic, lifestyle and health-related characteristics are associated
      with PSA testing, suggesting that observed associations of some of these traits
      with risk for prostate cancer in epidemiological studies may be, at least
      partially, due to detection bias.

PMID- 27693813
TI  - Irisin inhibition of growth hormone secretion in cultured tilapia pituitary
      cells.
AB  - Irisin, the product of fibronectin type III domain-containing protein 5 (FNDC5)
      gene, is well-documented to be a regulator of energy metabolism. At present, not
      much is known about its biological function in non-mammalian species. In this
      study, a full-length tilapia FDNC5 was cloned and its tissue expression pattern
      has been confirmed. Based on the sequence obtained, we produced and purified
      recombinant irisin which could induce uncoupling protein 1 (UCP1) gene expression
      in tilapia hepatocytes. Further, the rabbit polyclonal irisin antiserum was
      produced and its specificity was confirmed by antiserum preabsorption. In tilapia
      pituitary cells, irisin inhibited growth hormone (GH) gene expression and
      secretion and triggered rapid phosphorylation of Akt, Erk1/2, and p38 MAPK.
      Furthermore, irisin-inhibited GH mRNA expression could be prevented by inhibiting
      PI3K/Akt, MEK1/2, and p38 MAPK, respectively. Apparently, fish irisin can act
      directly at the pituitary level to inhibit GH transcript expression via multiple
      signaling pathways.

PMID- 27693814
TI  - Retinal gap junctions are involved in rhythmogenesis of neuronal activity at
      remote locations - Study on infra-slow oscillations in the rat olivary pretectal
      nucleus.
AB  - A subpopulation of olivary pretectal nucleus (OPN) neurons fire action potentials
      in a rhythmic manner with an eruption of activity occurring approximately every
      two minutes. These infra-slow oscillations depend critically on functional
      retinal input and are subject to modulation by light. Interestingly, the activity
      of photoreceptors is necessary for the emergence of the rhythm and while classic
      photoreceptors (rods and cones) are necessary in darkness and dim light,
      melanopsin photoreceptors are indispensable in bright light. Using
      pharmacological and electrophysiological approaches in vivo, we show that also
      blocking retinal gap junctions (GJs), which are expressed by multitude of retinal
      cells, leads to the disruption of oscillatory activity in the rat OPN.
      Intravitreal injection of carbenoxolone (CBX) quenched oscillations in a
      concentration-dependent manner with 1mM being ineffective, 5mM showing partial
      and 20mM showing complete effectiveness in disrupting oscillations. Moreover, the
      most effective CBX concentration depressed cone-mediated light-induced responses
      of oscillatory neurons suggesting that CBX is also acting on targets other than
      GJs. In contrast, intravitreal injection of meclofenamic acid (MFA, 20mM) led to
      disruption of the rhythm but did not interfere with cone-mediated light-induced
      responses of oscillatory neurons, implying that MFA is more specific toward GJs
      than CBX, as suggested before. We conclude that electrical coupling between
      various types of retinal cells and resultant synchronous firing of retinal
      ganglion cells is necessary for the generation of infra-slow oscillations in the
      rat OPN.

PMID- 27693815
TI  - Congenital prosopagnosia is associated with a genetic variation in the oxytocin
      receptor (OXTR) gene: An exploratory study.
AB  - Face-recognition deficits, referred to with the term prosopagnosia (i.e., face
      blindness), may manifest during development in the absence of any brain injury
      (from here the term congenital prosopagnosia, CP). It has been estimated that
      approximately 2.5% of the population is affected by face-processing deficits not
      depending on brain lesions, and varying a lot in severity. The genetic bases of
      this disorder are not known. In this study we tested for genetic association
      between single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene
      (OXTR) and CP in a restricted cohort of Italian participants. We found evidence
      of an association between the common genetic variants rs53576 and rs2254298 OXTR
      SNPs and prosopagnosia. This association was also found when including an
      additional group of German individuals classified as prosopagnosic in the
      analysis. Our preliminary data provide initial support for the involvement of
      genetic variants of OXTR in a relevant cognitive impairment, whose genetic bases
      are still largely unexplored.

PMID- 27693816
TI  - A dynamic, sex-specific expression pattern of genes regulating thyroid hormone
      action in the developing zebra finch song control system.
AB  - The zebra finch (Taeniopygia guttata) song control system consists of several
      series of interconnected brain nuclei that undergo marked changes during ontogeny
      and sexual development, making it an excellent model to study developmental
      neuroplasticity. Despite the demonstrated influence of hormones such as sex
      steroids on this phenomenon, thyroid hormones (THs) - an important factor in
      neural development and maturation - have not been studied in this regard. We used
      in situ hybridization to compare the expression of TH transporters, deiodinases
      and receptors between both sexes during all phases of song development in male
      zebra finch. Comparisons were made in four song control nuclei: Area X, the
      lateral magnocellular nucleus of the anterior nidopallium (LMAN), HVC (used as
      proper name) and the robust nucleus of the arcopallium (RA). Most genes
      regulating TH action are expressed in these four nuclei at early stages of
      development. However, while general expression levels decrease with age, the
      activating enzyme deiodinase type 2 remains highly expressed in Area X, HVC and
      RA in males, but not in females, until 90days post-hatch (dph), which marks the
      end of sensorimotor learning. Furthermore, the L-type amino acid transporter 1
      and TH receptor beta show elevated expression in male HVC and RA respectively
      compared to surrounding tissue until adulthood. Differences compared to
      surrounding tissue and between sexes for the other TH regulators were minor.
      These developmental changes are accompanied by a strong local increase in
      vascularization in the male RA between 20 and 30dph but not in Area X or HVC. Our
      results suggest that local regulation of TH signaling is an important factor in
      the development of the song control nuclei during the song learning phase and
      that TH activation by DIO2 is a key player in this process.

PMID- 27693817
TI  - Role of potassium and pH on the initiation of sperm motility in the European eel.
AB  - The role of potassium from the seminal plasma and/or the activation media was
      examined by selectively removing K+ from this media, and by testing the use of K+
      channel inhibitors and a K-ionophore. Sperm motility was measured using a CASA
      system, intracellular K+ and pH were measured by flow cytometry, and sperm head
      area was measured by ASMA: Automated Sperm Morphometry Analyses. Sperm motility
      was notably inhibited by the removal of K+ from the seminal plasma and by
      treatment with the K+ ionophore valinomycin. This therefore indicates that a
      reduction of K+ levels in the quiescent stage inhibits further motility. The
      normal decrease in sperm head area induced by seawater activation was altered by
      the removal of K+ from the seminal plasma, and an increase in the pHi in the
      quiescent stage was also induced. Intracellular pH (pHi) was quantitatively
      measured for the first time in European eel spermatozoa, being 7.2 in the
      quiescent stage and 7.1 post-activation. Intracellular and external pH levels
      influenced sperm motility both in the quiescent stage and at activation. The
      alkalinization of the pHi (by NH4Cl) inhibited sperm motility activation, while
      acidification (by Na-acetate) did not have any effect. Our results indicate that
      a pH gradient between the sperm cell and the seminal plasma is necessary for
      sperm motility activation. The presence of the ion K+ in the seminal plasma (or
      in the extender medium) is necessary in order to maintain sperm volume,
      intracellular pH and sperm motility.

PMID- 27693818
TI  - Correlation of Homocysteine with Cerebral Hemodynamic Abnormality, Endothelial
      Dysfunction Markers, and Cognition Impairment in Patients with Traumatic Brain
      Injury.
AB  - OBJECTIVE: This study aimed to assess any correlation between serum levels of
      homocysteine (Hcy) and markers of cerebral hemodynamics, endothelial dysfunction,
      and cognition impairment in patients with traumatic brain injury (TBI). METHODS:
      By a cross-sectional study, all clinical data and serum levels of homocysteine of
      85 TBI patients were collected. The pulsatility indices (PIs) of the middle
      cerebral artery were recorded by transcranial color-coded Doppler ultrasonography
      and cerebrovascular reactivity was measured by the increase in middle cerebral
      artery flow velocity in response to 5% inhaled CO2. Serum levels of intercellular
      adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1), cognition
      status by Montreal Cognitive Assessment, and Mini-Mental State Examination were
      measured in all participants. RESULTS: Totally, 85 patients including 51.76% male
      and the mean age of 54.48 years were studied. The level of Hcy in patients who
      died in the hospital or during 6 months after TBI was significantly higher than
      in survivors (P = 0.045, P = 0.020, respectively). Also, the levels of ICAM-1,
      VCAM-1, and PI in deceased patients were higher than their figures in survivors
      in both hospital and 6-month follow-ups (P = 0.450, P = 0.000; P = 0.072, P =
      0.000, P = 0.090, and P = 0.000, respectively). Cerebrovascular reactivity in
      deceased patients was significantly lower than that in alive individuals (P =
      0.008 and P = 0.000, respectively). A significant correlation was found between
      Hcy with cognition impairment according to Montreal Cognitive Assessment, Mini
      Mental State Examination, and cerebral hemodynamic status according to PI (P =
      0.000 for all). Also, this correlation was shown between Hcy with ICAM-1 and VCAM
      1 in hospital and 6-month follow-ups (P = 0.000 for both). CONCLUSION: Hcy has a
      significant correlation with markers of cerebrovascular, endothelial, and
      cognition abnormality in TBI patients.

PMID- 27693819
TI  - Improving Traumatic Brain Injury Outcomes: The Development of an Evaluation and
      Referral Tool at Groote Schuur Hospital.
AB  - BACKGROUND: The Western Cape Province of South Africa has a great shortage of
      diagnostic expertise, rehabilitative infrastructure, and support services for
      patients with traumatic brain injury (TBI). The neurosurgical outpatient setting
      is busy and often chaotic, and patients are frequently lost to follow-up. This
      study sought to continue with the design and development of a comprehensive, yet
      brief tool to aid patient referrals and ensure that no consequence of TBI is left
      unidentified and unaddressed. METHODS: There were 47 patients with TBI (mean age,
      35 years; range, 18-75 years) assessed. The study was designed in 3 distinct
      phases, each representing a different stage in the tool's development. RESULTS:
      The Groote Schuur Traumatic Brain Injury Evaluation was shortened and simplified.
      Overall, 81% of the participants indicated cognitive dysfunction. There was a
      high prevalence of psychological/psychiatric sequelae, with 85% of participants
      reporting at least 1 such problem. CONCLUSIONS: The findings further highlight
      the prevalence of the cognitive, behavioral, and psychological consequences of
      TBI and shed additional light on the particular types of problems that patients
      with TBI face. Following the identified changes, the questionnaire and algorithm
      combination are now ready to be validated in the neurosurgical clinical setting.

PMID- 27693820
TI  - Orbitozygomatic Craniotomy with Modified Zabramski's Technique: A Technical Note
      and Anatomic and Clinical Findings.
AB  - BACKGROUND: The surgical technique of orbitozygomatic craniotomy reported by
      Zabramski et al. is an excellent procedure, facilitating wide surgical exposure,
      easy orbital reconstruction, and a satisfactory postsurgical aesthetic outcome;
      however, it is anatomically complicated and technically difficult. We introduce a
      simplified technique of Zabramski's orbitozygomatic craniotomy and present the
      anatomic and clinical findings with cadaveric photos, illustrations, and a video.
      METHODS: The orbitozygomatic craniotomy was performed on 20 sides of 11 cadaveric
      heads, in which the cut between the inferior orbital fissure and superior orbital
      fissure was modified and simplified, and the shortest distance between them was
      measured. This technique was applied to 13 clinical cases, and craniotomy
      associated aesthetic and functional complications were evaluated. RESULTS: The
      average of the shortest distance from the inferior orbital fissure to superior
      orbital fissure was 21.3 mm (range, 19-23 mm) on the 20 sides of the 11 cadaveric
      heads. In all 13 clinical cases, orbitozygomatic craniotomy could be achieved in
      a short time, while preserving the structure of the orbital wall. A hollow at the
      temple was noted in 1 patient, cerebrospinal fluid leak occurred in 2 patients,
      and transient facial pain occurred in 1 patient; however, no other craniotomy
      associated aesthetic or functional complications, including enophthalmos, were
      found in any of the 13 patients. CONCLUSIONS: With this modified technique,
      Zabramski's ideal orbitozygomatic craniotomy could be achieved easily with only
      minimal complications, while realizing all advantages of the technique.

PMID- 27693821
TI  - Post-Traumatic Tremor and Thalamic Deep Brain Stimulation: Evidence for Use of
      Diffusion Tensor Imaging.
AB  - BACKGROUND: Deep brain stimulation (DBS) is a well-established treatment to
      reduce tremor, notably in Parkinson disease. DBS may also be effective in post
      traumatic tremor, one of the most common movement disorders caused by head
      injury. However, the cohorts of patients often have multiple lesions that may
      impact the outcome depending on which fiber tracts are affected. CASE
      DESCRIPTION: A 20-year-old man presented after road traffic accident with severe
      closed head injury and polytrauma. Computed tomography scan showed left frontal
      and basal ganglia hemorrhagic contusions and intraventricular hemorrhage. A
      disabling tremor evolved in step with motor recovery. Despite high-intensity
      signals in the intended thalamic target, a visual analysis of the preoperative
      diffusion tensor imaging revealed preservation of connectivity of the intended
      target, ventralis oralis posterior thalamic nucleus (VOP). This was confirmed by
      the postoperative tractography study presented here. DBS of the VOP/zona incerta
      was performed. Six months postimplant, marked improvement of action (postural,
      kinetic, and intention) tremor was achieved. CONCLUSIONS: We demonstrated a
      strong connectivity between the VOP and the superior frontal gyrus containing the
      premotor cortex and other central brain areas responsible for movement control.
      In spite of an existing lesion in the target, the preservation of these tracts
      may be relevant to the improvement of the patient's symptoms by DBS.

PMID- 27693822
TI  - Flow Diversion for Treatment of Growing A2 Aneurysm in a Child: Case Report and
      Review of Flow Diversion for Intracranial Aneurysms in Pediatric Patients.
AB  - BACKGROUND: Intracranial flow diversion has gained increasing popularity since
      the approval of the Pipeline Embolization Device (PED). Although it is only
      approved for use in adult patients, the PED has been used to treat aneurysms in
      pediatric patients. We present the first reported case of the use of a PED in a
      pediatric patient to treat an unusual fusiform distal anterior cerebral artery
      aneurysm. CASE DESCRIPTION: A 12-year-old girl presented with new onset seizures
      and was found to have a distal left anterior cerebral artery aneurysm. Initially,
      this was managed conservatively, but follow-up imaging performed 4 months after
      presentation demonstrated enlargement of the aneurysm. The patient underwent
      endovascular embolization of her aneurysm with PED. This was successfully
      performed and the patient recovered from the procedure with no neurologic
      deficits. CONCLUSIONS: Follow-up digital subtraction angiography and magnetic
      resonance angiography at 6 and 12 months, respectively, showed complete occlusion
      of the aneurysm. We also reviewed the literature on flow diversion for treatment
      of pediatric intracranial aneurysms.

PMID- 27693823
TI  - The non-medical workforce and its role in surgical training: Consensus
      recommendations by the Association of Surgeons in Training.
AB  - Changes in the delivery of the healthcare structure have led to the expansion of
      the non-medical workforce (NMW). The non-medical practitioner in surgery (a
      healthcare professional without a medical degree who undertakes specialist
      training) is a valuable addition to a surgical firm. However, there are a number
      of challenges regarding the successful widespread implementation of this role.
      This paper outlines a number of these concerns, and makes recommendations to aid
      the realisation of the non-medical practitioner as a normal part of the surgical
      team. In summary, the Association of Surgeons in Training welcomes the
      development of the non-medical workforce as part of the surgical team in order to
      promote enhanced patient care and improved surgical training opportunities.
      However, establishing a workforce of independent/semi-independent practitioners
      who compete for the same training opportunities as surgeons in training may
      threaten the UK surgical training system, and therefore the care of our future
      patients.

PMID- 27693824
TI  - Advanced vessel sealing devices in total thyroidectomy for substernal goitre: A
      retrospective cohort study.
AB  - INTRODUCTION: When total thyroidectomy is performed for substernal goitre, a high
      risk of morbidity is reported. Advanced vessel sealing devices provide an
      alternative to the conventional clamp and tie technique. The aim of this study is
      to compare the outcome of patients who underwent total thyroidectomy for
      substernal goitre using Ligasure Small Jaw, Harmonic Focus, or conventional
      technique. METHODS: Between 2011 and 2014, from a population of 393 patients
      undergoing surgery for thyroid disease, 75 (49 females, 26 males, mean age: 57.9
      years; range: 28-83 years) underwent total thyroidectomy by the same surgeon for
      substernal goitre. Patients were divided into three groups: group A (n = 26) in
      which total thyroidectomy was performed using conventional technique; group B (n
      = 22), and group C (n = 27) in which total thyroidectomy was performed using
      Ligasure Small Jaw and Harmonic Focus, respectively. Operative time, time to
      drain removal, hospitalization and morbidity (hypoparathyroidism, vocal cord
      palsy, haemorrhage, seroma, other) were analyzed. RESULTS: Mean duration of
      surgery was 136.5 +/- 26.7 min in group A vs 110.5 +/- 24.8 in B, and 101.6 +/-
      25.4 in C, with significant statistical differences between A vs B (p < 0.005)
      and C (p < 0.0001). There was no mortality. The overall morbidity was 29.3%.
      There was no significant difference in time to drain removal, postoperative
      hospitalization, and morbidity among the three groups. CONCLUSION: This is the
      first study analyzing advanced vessel sealing devices in total thyroidectomy for
      substernal goitre in the literature. The use of advanced vessel sealing devices
      significantly reduces operative time of total thyroidectomy performed for
      substernal goitre but does not seem to affect the other evaluated outcomes.

PMID- 27693825
TI  - Transforaminal endoscopic system technique for discogenic low back pain: A
      prospective Cohort study.
AB  - OBJECTIVE: To investigate the clinical outcomes of transforaminal endoscopic
      system(TESSYS) for discogenic low back pain(DLBP). METHODS: 62 consecutive
      patients with one-level DLBP applying to the including criteria underwent TESSYS
      from January 2010 to December 2013. These patients included 38 males and 24
      females with a mean age of 42.7 +/- 5.4 years (range, 18-73 yr) and a mean follow
      up of 26.8 +/- 4.2 months (range, 12-48 months). The visual analog scale (VAS)
      were used for back pain, the Oswestry Disability Index (ODI) for lumbar function,
      and the modified MacNab criteria for clinical global outcomes. RESULTS: 24
      patients showed only inflammatory granuloma on annulus tear tissues(Group A), 16
      patients showed no annulus tear but adhesion and inflammatory granuloma among the
      intracanal annulus fibrous(AF), posterior longitudinal ligament(PLL) and the
      abdomen side of the dura sac(Group B) and 22 patients showed both(Group C).
      Concordant pain could be triggered by touching the inflammation with the bipolar
      radiofrequency probe. The success rate (excellent and good) of group C was much
      higher than A and B(P < 0.05). The whole success rate was 75.8%. Of the 4
      patients with poor result, 2 refused further surgical treatment and showed either
      no improvement or worsening. The remaining 2 patients had spinal fusion surgery
      and achieved better results. VAS and ODI had significantly improved after surgery
      (P < 0.01). No unexpected complications were seen. CONCLUSION: TEEYS is an
      effective method in treating DLBP and the complete management of the inflammatory
      granuloma was the key point in achieving better results.

PMID- 27693826
TI  - Pornography classification: The hidden clues in video space-time.
AB  - As web technologies and social networks become part of the general public's life,
      the problem of automatically detecting pornography is into every parent's mind -
      nobody feels completely safe when their children go online. In this paper, we
      focus on video-pornography classification, a hard problem in which traditional
      methods often employ still-image techniques - labeling frames individually prior
      to a global decision. Frame-based approaches, however, ignore significant cogent
      information brought by motion. Here, we introduce a space-temporal interest point
      detector and descriptor called Temporal Robust Features (TRoF). TRoF was custom
      tailored for efficient (low processing time and memory footprint) and effective
      (high classification accuracy and low false negative rate) motion description,
      particularly suited to the task at hand. We aggregate local information extracted
      by TRoF into a mid-level representation using Fisher Vectors, the state-of-the
      art model of Bags of Visual Words (BoVW). We evaluate our original strategy,
      contrasting it both to commercial pornography detection solutions, and to BoVW
      solutions based upon other space-temporal features from the scientific
      literature. The performance is assessed using the Pornography-2k dataset, a new
      challenging pornographic benchmark, comprising 2000 web videos and 140h of video
      footage. The dataset is also a contribution of this work and is very assorted,
      including both professional and amateur content, and it depicts several genres of
      pornography, from cartoon to live action, with diverse behavior and ethnicity.
      The best approach, based on a dense application of TRoF, yields a classification
      error reduction of almost 79% when compared to the best commercial classifier. A
      sparse description relying on TRoF detector is also noteworthy, for yielding a
      classification error reduction of over 69%, with 19* less memory footprint than
      the dense solution, and yet can also be implemented to meet real-time
      requirements.

PMID- 27693827
TI  - Further investigations into the single metal deposition (SMD II) technique for
      the detection of latent fingermarks.
AB  - Single metal deposition (SMD II), a recently proposed method for the development
      of latent fingermarks, was investigated by systematically altering aspects of the
      procedure to assess their effect on the level of development and contrast
      achieved. Gold nanoparticle size, temperature of the deposition solution bath,
      and orbital shaking during detection were shown to affect the levels of
      development and contrast obtained. Gold nanoparticles of diameter 15-21nm were
      found to be most effective for satisfactory visualisation of latent fingermarks,
      while solutions that were applied at room temperature were found to adequately
      balance the ratio between the contrast of the fingermark ridge detail and the
      level of background staining achieved. Finally, optimum levels of development and
      contrast were obtained through constant agitation of both solution baths at
      approximately 50RPM throughout the submersion time. SMD II was also tested on a
      large variety of substrate types and shown to be effective on a range of porous,
      non-porous, and semi-porous surfaces; however, the detection quality can be
      significantly influenced by the substrate nature. This resulted in the production
      of dark grey, white, or gold coloured fingermarks on different surfaces, as well
      as reversed detection on certain types of plastic, similarly seen through the use
      of vacuum metal deposition.

PMID- 27693828
TI  - Ecological effects on arbovirus-mosquito cycles of transmission.
AB  - Mosquitoes transmit many viruses to a variety of hosts. Cycles of mosquito borne
      arbovirus transmission are the result of complex interactions between the
      mosquito, the arbovirus and the host that are influenced by genetic variations in
      a variety of traits in each that are all influenced by many environmental
      factors. R0, the basic reproduction number or mean number of individuals infected
      from a single infected individual, is a measure of mosquito borne arbovirus
      transmission. Understanding the causes for the distribution of R0 in any
      transmission cycle is a daunting challenge due to the lack of information on the
      genetic and environmental variances that influence R0. Information about the
      major factors influencing R0 for specific transmission cycles is essential to
      develop efficient and effective strategies to reduce transmission in different
      cycles and locations.

PMID- 27693829
TI  - Extinction and renewal of cue-elicited reward-seeking.
AB  - Reward cues can contribute to overconsumption of food and drugs and can relapse.
      The failure of exposure therapies to reduce overconsumption and relapse is
      generally attributed to the context-specificity of extinction. However, no
      previous study has examined whether cue-elicited reward-seeking (as opposed to
      cue-reactivity) is sensitive to context renewal. We tested this possibility in
      160 healthy volunteers using a Pavlovian-instrumental transfer (PIT) design
      involving voluntary responding for a high value natural reward (chocolate). One
      reward cue underwent Pavlovian extinction in the same (Group AAA) or different
      context (Group ABA) to all other phases. This cue was compared with a second non
      extinguished reward cue and an unpaired control cue. There was a significant
      overall PIT effect with both reward cues eliciting reward-seeking on test
      relative to the unpaired cue. Pavlovian extinction substantially reduced this
      effect, with the extinguished reward cue eliciting less reward-seeking than the
      non-extinguished reward cue. Most interestingly, extinction of cue-elicited
      reward-seeking was sensitive to renewal, with extinction less effective for
      reducing PIT when conducted in a different context. These findings have important
      implications for extinction-based interventions for reducing maladaptive reward
      seeking in practice.

PMID- 27693831
TI  - Regulation of the assembly and amyloid aggregation of murine amylin by zinc.
AB  - The secretory granule of the pancreatic beta-cells is a zinc-rich environment
      copopulated with the hormones amylin and insulin. The human amylin is shown to
      interact with zinc ions with major contribution from the single histidine
      residue, which is absent in amylin from other species such as cat, rhesus and
      rodents. We report here the interaction of murine amylin with zinc ions in vitro.
      The self-assembly of murine amylin is tightly regulated by zinc and pH. Ion
      mobility mass spectrometry revealed zinc interaction with monomers and oligomers.
      Nuclear magnetic resonance confirms the binding of zinc to murine amylin. The
      aggregation process of murine amylin into amyloid fibrils is accelerated by zinc.
      Collectively these data suggest a general role of zinc in the modulation of
      amylin variants oligomerization and amyloid fibril formation.

PMID- 27693832
TI  - Thermal, emulsifying and rheological properties of polysaccharides sequentially
      extracted from Vaccinium bracteatum Thunb leaves.
AB  - Plant polysaccharides are widely used in food industry as thickening and gelling
      agents and these attributes largely depend on their thermal, emulsifying and
      rheological properties. As known, the extraction methods always bring about the
      diversification of property and functions of polysaccharides. Thus, the Vaccinium
      bracteatum Thunb leaves polysaccharides (VBTLP) were sequentially extracted using
      hot buffer (HBSS), chelating agent (CHSS), dilute alkaline (DASS) and
      concentrated alkaline (CASS). The thermal, emulsifying and rheological properties
      of VBTLP were investigated in the present study. Within the range of 20-225
      degrees C, CHSS showed the highest peak temperature, whereas HBSS displayed the
      highest endothermic enthalpy and highest emulsifying activity, while, CASS showed
      the longest emulsifying stability. The VBTLP solutions exhibited non-Newtonian
      shear-thinning behavior within the concentrations of 0.6-2.5%. The apparent
      viscosity of VBTLP solution decreased under following conditions: acidic pH
      (4.0), alkaline pH (10.0), in the presence of Ca2+ and at high temperature, while
      it increased in the presence of Na+ and at freezing conditions. The modulus G'
      and G" of VBTLP solutions were increased with increasing oscillation frequency,
      and the crossover frequency shifted to lower values when the polysaccharide
      content increased. The above results of thermal, emulsifying and rheological
      properties of VBTLPs supplied the basis for V. bracteatum leaves in potential
      industrial applications of foods.

PMID- 27693833
TI  - Monosaccharide composition of acidic gum exudates from Indian Acacia tortilis
      ssp. raddiana (Savi) Brenan.
AB  - Acacia tortilis ssp. raddiana (Savi) Brenan commonly known as Israeli Babool has
      contributed immensely for sand dunes management in Indian desert leading to wind
      erosion control and increased biological productivity. The species is extensively
      used in traditional medicine system for a number of therapeutic applications and
      as nutraceutical. The polysaccharide was isolated in 43.6% yield from gum
      exudates. The monosaccharides, L-arabinose, D-galactose D-glucose, L-rhamnose and
      D-mannose were determined in molar ratio of 78.1%, 18.64%, 0.60%, 1.71% and 0.74%
      respectively. The molar ratio of uronic acids was studied using diverse
      spectrophotometric methods and compared with GLC. The content of D-galacturonic
      acid and D-glucuronic was determined as 3.88% and 4.35% respectively by GLC. The
      results were compared with the spectrophotometric methods. The results using DMP
      as chromogenic reagent are closer to that obtained by GLC. Structural analysis of
      the polysaccharide may provide scientific basis for nutraceutical, pharmaceutical
      and biological applications of gum exudates from A. tortilis, which is
      extensively planted in India.

PMID- 27693830
TI  - Nutrition and other lifestyle influences on arterial aging.
AB  - As our world's population ages, cardiovascular diseases (CVD) will become an
      increasingly urgent public health problem. A key antecedent to clinical CVD and
      many other chronic disorders of aging is age-related arterial dysfunction,
      characterized by increased arterial stiffness and impaired arterial endothelial
      function. Accumulating evidence demonstrates that diet and nutrition may
      favorably modulate these arterial functions with aging, but many important
      questions remain. In this review, we will summarize the available information on
      dietary patterns and nutritional factors that have been studied for their
      potential to reduce arterial stiffness and improve endothelial function with age,
      with an emphasis on: 1) underlying physiological mechanisms, and 2) emerging
      areas of research on nutrition and arterial aging that may hold promise for
      preventing age-related CVD.

PMID- 27693835
TI  - Structural elucidation of anti-metastatic rhamnogalacturonan II from the
      pectinase digest of citrus peels (Citrus unshiu).
AB  - The aim of this study was to characterize a polysaccharide found in citrus peels
      with an anti-metastatic property. CPE-II was purified by the pectinase digestion
      of citrus peels. During in vivo lung metastasis of Colon26-M3.1, administration
      of 10MUg of CPE-II per mouse showed 81.3% inhibition of metastasis. CPE-II
      consists of 15 different monosaccharides and 22 different glycosyl linkages,
      characteristic of rhamnogalacturonan II (RG-II). The primary structure was
      elucidated based on sugar composition, methylation analysis, oligosaccharide
      analysis, and sequencing using GC, GC-MS, LC-MS, and ESI-MS/MS analyses.
      Sequential degradation using partial acid hydrolysis indicated that CPE-II
      contained Rhap-(1->5)-Kdo, Araf-(1->5)-Dha, an AceA-containing nonasaccharide,
      and an uronic acid-rich oligosaccharide in addition to an alpha-(1->4)
      galacturono-oligosaccharide main chain. The molecular weight of CPE-II was
      observed to decrease from 9 to 5kDa at a pH value of <2.0, as observed by HPSEC.
      Thus, we propose that the anti-metastatic CPE-II is primarily present as an RG-II
      dimer.

PMID- 27693834
TI  - Effects of polysaccharide from mycelia of Ganoderma lucidum on intestinal barrier
      functions of rats.
AB  - The intestinal mucosal barriers play essential roles not only in the digestion
      and absorption of nutrients, but also the innate defense against most intestinal
      pathogens. In the present study, polysaccharide from the mycelia of Ganoderma
      lucidum was given via oral administration to rats (100mg/kg body weight, 21days)
      to investigate its effects on intestinal barrier functions, including the
      mechanical barrier, immunological barrier and biological barrier function. It was
      found that the polysaccharide administration could significantly up-regulate the
      expression of occludin, nuclear factor-kappaB p65 (NF-kappaB p65) and secretory
      immunoglobulin A (SIgA) in ileum, markedly improve the levels of interferon-gamma
      (IFN-gamma), interleukin-2 (IL-2), and IL-4, and decrease the level of diamine
      oxidase (DAO) in serum. Meanwhile, rats from the polysaccharide group showed
      significant higher microbiota richness in cecum as reflected by the Chao 1 index
      compared with the control group. Moreover, the polysaccharide decreased the
      Firmicutes-to-Bacteroidetes ratio. Our results indicated that the polysaccharide
      from the mycelia of G. lucidum might be used as functional agent to regulate the
      intestinal barrier functions.

PMID- 27693836
TI  - The effect of a patient centred care bundle intervention on pressure ulcer
      incidence (INTACT): A cluster randomised trial.
AB  - BACKGROUND: Hospital-acquired pressure ulcers are a serious patient safety
      concern, associated with poor patient outcomes and high healthcare costs. They
      are also viewed as an indicator of nursing care quality. OBJECTIVE: To evaluate
      the effectiveness of a pressure ulcer prevention care bundle in preventing
      hospital-acquired pressure ulcers among at risk patients. DESIGN: Pragmatic
      cluster randomised trial. SETTING: Eight tertiary referral hospitals with >200
      beds each in three Australian states. PARTICIPANTS: 1600 patients (200/hospital)
      were recruited. Patients were eligible if they were: >=18 years old; at risk of
      pressure ulcer because of limited mobility; expected to stay in hospital >=48h
      and able to read English. METHODS: Hospitals (clusters) were stratified in two
      groups by recent pressure ulcer rates and randomised within strata to either a
      pressure ulcer prevention care bundle or standard care. The care bundle was
      theoretically and empirically based on patient participation and clinical
      practice guidelines. It was multi-component, with three messages for patients'
      participation in pressure ulcer prevention care: keep moving; look after your
      skin; and eat a healthy diet. Training aids for patients included a DVD, brochure
      and poster. Nurses in intervention hospitals were trained in partnering with
      patients in their pressure ulcer prevention care. The statistician, recruiters,
      and outcome assessors were blinded to group allocation and interventionists
      blinded to the study hypotheses, tested at both the cluster and patient level.
      The primary outcome, incidence of hospital-acquired pressure ulcers, which
      applied to both the cluster and individual participant level, was measured by
      daily skin inspection. RESULTS: Four clusters were randomised to each group and
      799 patients per group analysed. The intraclass correlation coefficient was
      0.035. After adjusting for clustering and pre-specified covariates (age, pressure
      ulcer present at baseline, body mass index, reason for admission, residence and
      number of comorbidities on admission), the hazard ratio for new pressure ulcers
      developed (pressure ulcer prevention care bundle relative to standard care) was
      0.58 (95% CI: 0.25, 1.33; p=0.198). No adverse events or harms were reported.
      CONCLUSIONS: Although the pressure ulcer prevention care bundle was associated
      with a large reduction in the hazard of ulceration, there was a high degree of
      uncertainty around this estimate and the difference was not statistically
      significant. Possible explanations for this non-significant finding include that
      the pressure ulcer prevention care bundle was effective but the sample size too
      small to detect this.

PMID- 27693837
TI  - Massive upper gastrointestinal bleeding due to splenoportal axis thrombosis in a
      patient with a tested JAK2 mutation: A case report and review literature.
AB  - Portal hypertension is a clinical syndrome defined as a portal venous pressure
      that exceeds 10mmHg. Cirrhosis is the most common cause of portal hypertension
      and thrombosis of the splenoportal axis not associated with liver cirrhosis is
      the second cause of portal hypertension in the Western world. The primary
      myeloproliferative disorders are the main cause of portal venous thrombosis and
      somatic mutation of Janus Kinase 2 gene (JAK2 V617F) can be found in
      approximately 90% of polycythemia vera, 50% of essential thrombocyrosis and 50%
      primary myelofibrosis. A a 55-year-old man with JAK2 mutation-associated
      splenoportal axis hypertension and bleeding complications due to oesophageal
      varices is reported. A massive upper bleeding episode made an emergent surgery to
      be done immediatelly at seventh day. The patient was discharged home at fifteenth
      day after surgery.

PMID- 27693838
TI  - Pure small cell carcinoma of the prostate preceded by acute zonal occult outer
      retinopathy: A case report.
AB  - INTRODUCTION: Pure small cell prostate cancer (SCPC) cases are very rare. Acute
      zonal occult outer retinopathy (AZOOR) has been described as a non-neoplastic
      retinopathy. We report the first case of pure SCPC preceded by AZOOR in the
      literature. CASE REPORT: A 59year old gentleman presented with an obstructed
      infected urinary system. He had a diagnosis of AZOOR 6 months ago that was
      investigated with full body imaging without any suspicious findings. However, the
      most recent CT findings demonstrated extensive disease dissemination. The patient
      underwent rigid cystoscopy and resection that confirmed a diagnosis of pure SCPC.
      DISCUSSION: AZOOR is a clinical syndrome of photopsia and rapid zonal field loss.
      The exact aetiology remains unknown and its association with malignancy remains
      contentious. Paraneoplastic manifestations of unexplained visual loss in SCPC are
      rare with only 2 cases reported in the literature. There are no cases
      demonstrating an association between AZOOR and SCPC. CONCLUSION: Pure SCPC is an
      aggressive malignancy with most cases presenting with extensive disease
      dissemination on diagnosis. Early detection has a role in improving prognosis but
      is challenging. Further research is required to establish a standard treatment
      protocol.

PMID- 27693839
TI  - Intravenous vs intraperitoneal transplantation of umbilical cord mesenchymal stem
      cells from Wharton's jelly in the treatment of streptozotocin-induced diabetic
      rats.
AB  - AIM: To evaluate the efficiency of mesenchymal stem cells isolated from Wharton's
      jelly (WJ-MSCs) through either the intravenous or intraperitoneal
      transplantations into streptozotocin (STZ)-induced diabetic rats as a therapy for
      type 1 diabetes mellitus (T1DM). METHODOLOGY: A rat model with STZ induction was
      established and the rats were divided into 3 groups: a tail vein injection group,
      an intraperitoneal injection group and a STZ control group. Following
      transplantation, blood glucose levels were monitored weekly then the pancreatic
      tissues were collected to examine the pancreatic islets by histopathology and
      morphometric studies. RESULTS: Intravenous transplantation of WJ-MSCs ameliorated
      hyperglycemia at day 7 after transplantation, with sustained decreased fasting
      blood glucose (FBG) levels until day 56. Further, these cells ameliorated at
      least partially the damage induced by STZ in the pancreas and produced a similar
      morphology to normal islets. On the contrary, intraperitoneal transplantation of
      WJ-MSCs failed to maintain normoglycemia or ameliorate the damaged pancreas in
      STZ-injected rats. CONCLUSION: These findings conclude that the intravenous
      administration method was effective in transplanting WJ-MSCs for the treatment of
      T1DM, whereas the intraperitoneal transplantation showed no therapeutic effect in
      our animal experiments.

PMID- 27693841
TI  - Gardenia jasminoides extract-capped gold nanoparticles reverse hydrogen peroxide
      induced premature senescence.
AB  - This study reports a green approach for synthesis of gold nanoparticles using
      Gardenia jasminoides extract, and specifically, can potentially enhance anti
      senescence activity. Biological synthesis of gold nanoparticles is ecofriendly
      and effective for the development of environmentally sustainable nanoparticles
      compared with existing methods. Here, we developed a simple, fast, efficient, and
      ecofriendly approach to the synthesis of gold nanoparticles by means of a
      Gardenia jasminoides extract. These G. jasminoides extract-capped gold
      nanoparticles (GJ-GNPs) were characterized by UV-vis, high resolution
      transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), and Furrier
      transform infrared spectroscopy (FT-IR). The synthesized GJ-GNPs turned red and
      showed maximal absorbance at 540nm. Thus, GJ-GNPs were synthesized successfully.
      We hypothesized that GJ-GNPs would protect ARPE19 cells from hydrogen peroxide
      induced premature senescence. SA-beta-gal activity was elevated in hydrogen
      peroxide-treated cells, however, this effect was attenuated by GJ-GNP treatment.
      Moreover, compared with the normal control, hydrogen peroxide treatment
      significantly increased lysosome content of the cells and production of reactive
      oxygen species (ROS). GJ-GNPs effectively attenuated the increase in lysosome
      content and ROS production in these senescent cells. According to cell cycle
      analysis, G2/M arrest was promoted by hydrogen peroxide treatment in ARPE19
      cells, however, this change was reversed by GJ-GNPs. Western blot analysis showed
      that treatment with GJ-GNPs increased the expression of p53, p21, SIRT3, HO-1,
      and NQO1 in senescent cells. Our findings should advance the understanding of
      premature senescence and may lead to therapeutic use of GJ-GNPs in retina-related
      regenerative medicine.

PMID- 27693840
TI  - Clinical predictors differentiating non-diabetic renal diseases from diabetic
      nephropathy in a large population of type 2 diabetes patients.
AB  - AIMS: Non-diabetic renal diseases (NDRDs) are associated with better renal
      outcomes than diabetic nephropathy (DN). This study was conducted to determine
      the common clinical markers predicting NDRDs in type 2 diabetes patients.
      METHODS: Patients with type 2 diabetes mellitus who underwent a renal biopsy were
      screened. Eligible patients were categorized into two groups: DN group and NDRD
      group. Patient's clinical characteristics and laboratory data were collected.
      Logistic regression analysis was performed to identify risk factors for NDRD
      development, and the diagnostic performance of these variables was evaluated.
      RESULTS: The study included 248 patients, 96 (38.71%) in the DN group and 152
      (61.29%) in the NDRD group. Patients in the NDRD group had a shorter duration of
      DM and higher hemoglobin, estimated glomerular filtration rate, and urine osmotic
      pressure values as well as a higher incidence of glomerular hematuria than
      patients in the DN group. In the NDRD patients, the most common pathological type
      was membranous nephropathy (55, 36.18%). Absence of retinopathy (OR, 44.696, 95%
      CI, 15.91-125.566), glomerular hematuria (OR, 9.587, 95% CI, 2.027-45.333), and
      DM history ?5years (OR, 4.636, 95% CI, 1.721-12.486) were significant and
      independent risk factors for the development of NDRD (P<0.01). Absence of
      retinopathy achieved the overall highest diagnostic efficiency with a sensitivity
      of 92.11% and specificity of 82.29%. Glomerular hematuria had the highest
      specificity (93.75%). CONCLUSION: Shorter duration of diabetes (?5years), absence
      of retinopathy, and presence of glomerular hematuria were independent indicators
      associated with NDRDs, indicating the need for renal biopsy.

PMID- 27693842
TI  - New insights into the dimerization and site-specific cooperative interaction of
      Azure B with model transport proteins by spectroscopic and computational studies.
AB  - In the present study, the interaction of model transport proteins Human serum
      albumin (HSA) and Bovine serum albumin (BSA) with a photoactive dye, Azure B
      (AZB) were studied by spectroscopic and in silico methods. The absorption
      spectral behavior of AZB in the presence of varying concentrations of serum
      albumins (HSA and BSA) revealed the formation of dye aggregates within the
      protein cavity. The binding parameters computed from the emission quenching data
      showed that AZB bind to HSA and BSA with significant affinity and it was revealed
      that both the serum proteins (HSA and BSA) can bind AZB at more than one binding
      sites having at least one high-affinity binding site with different affinities
      (non-independent). The existence of static quenching mechanism was further
      evidenced from the time-resolved fluorescence spectroscopic analysis. Site
      competitive replacement experiments with specific site markers showed that AZB
      binds to site I of HSA and BSA. AutoDock based blind docking approach and
      molecular dynamics simulation studies were used to analyze the most probable
      binding location of AZB in HSA and BSA. The AZB induced unfolding of HSA and BSA
      was established by using absorption, circular dichroism and FT-IR spectral
      studies. The influence of AZB complexation on the biological function of HSA and
      BSA was evaluated by probing the hydrolysis of p-nitrophenyl acetate.

PMID- 27693843
TI  - Degradation of tyrosine and tryptophan residues of peptides by type I
      photosensitized oxidation.
AB  - Pterin derivatives are involved in various biological functions, including
      enzymatic processes that take place in human skin. Unconjugated oxidized pterins
      are efficient photosensitizers under UV-A irradiation and accumulate in the skin
      of patients suffering from vitiligo, a chronic depigmentation disorder. These
      compounds are able to photoinduce the oxidation of the peptide alpha-melanocyte
      stimulating hormone (alpha-MSH), which stimulates the production and release of
      melanin by melanocytes in skin and hair. In the present work we have used two
      peptides in which the amino acid sequence of alpha-MSH was mutated to
      specifically investigate the reactivity of tryptophan (Trp) and tyrosine residues
      (Tyr). The parent compound of oxidized pterins (Ptr) was used as a model
      photosensitizer in aqueous solution at pH5.5 and was exposed to UV-A radiation, a
      wavelength range where the peptides do not absorb. Trp residue yields N
      formylkynurenine and hydroxytryptophan as oxidized products, whereas the Tyr
      undergoes dimerization and incorporation of oxygen atoms. In both cases, the
      first step of the mechanism involves an electron transfer from the amino acid to
      the photosensitizer triplet excited state, Ptr is not consumed and hydrogen
      peroxide (H2O2) is released. The role of singlet oxygen produced by energy
      transfer from 3Ptr* to dissolved O2 was negligible or minor. Other amino acid
      residues, such as histidine, might be also affected.

PMID- 27693844
TI  - Trehalose protects Mn-depleted photosystem 2 preparations against the donor-side
      photoinhibition.
AB  - Recently, it has been shown that the addition of 1M trehalose leads to the
      increase of the rate of oxygen photoconsumption associated with activation of
      electron transport in the reaction center of photosystem 2 (PS2) in Mn-depleted
      PS2 membranes (apo-WOC-PS2) [37]. In the present work the effect of trehalose on
      photoinhibition of apo-WOC-PS2 preparations (which are characterized by a high
      sensitivity to the donor side photoinhibition of PS2) was investigated. The
      degree of photoinhibition was estimated by the loss of the capability of
      exogenous electron donor (sodium ascorbate) to reactivate the electron transport
      (measured by light-induced changes of chlorophyll fluorescence yield (?F)) in apo
      WOC-PS2. It was found that 1M trehalose enhanced the Mn2+-dependent suppression
      of photoinhibition of apo-WOC-PS2: in the presence of trehalose the addition of
      0.2MUM Mn2+ (corresponding to 2 Mn2+ per one reaction center) was sufficient for
      an almost complete suppression of the donor side photoinhibition of the complex.
      In the absence of trehalose it was necessary to add 100MUM Mn2+ to achieve a
      similar result. The effect of trehalose was observed during photoinhibition of
      apo-WOC-PS2 at low (15MUmolphotons-1m-2) and high (200MUmolphotons-1m-2) light
      intensity. When Mn2+ was replaced by other PS2 electron donors (ferrocyanide,
      DPC) as well as by Ca2+ the protective effect of trehalose was not observed. It
      was also found that 1M trehalose decreased photoinhibition of apo-WOC-PS2 if the
      samples contained endogenous manganese (1-2 Mn ions per one RC was enough for the
      maximum protection effect). It is concluded that structural changes in PS2 caused
      by the addition of trehalose enhance the capability of photochemical reaction
      centers of apo-WOC-PS2 to accept electrons from manganese (both exogenous and
      endogenous), which in turn leads to a considerable suppression of the donor side
      photoinhibition of PS2.

PMID- 27693845
TI  - Anti-inflammatory and anti-fibrinolytic effects of thrombomodulin alfa through
      carboxypeptidase B2 in the presence of thrombin.
AB  - BACKGROUND: Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances
      activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2
      (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities. Therefore, TM
      alfa may also have anti-inflammatory and anti-fibrinolytic effects through CPB2.
      However, these effects of TM alfa have not been elucidated. In the present study,
      we investigated the effects of TM alfa on inactivation of complement component
      C5a as an anti-inflammatory effect and prolongation of clot lysis time as an anti
      fibrinolytic effect via CPB2 in vitro. METHODS: CPB2 activity and tissue factor
      induced thrombin generation was examined by a chromogenic assay. C5a inactivation
      was evaluated by C-terminal cleavage of C5a and inhibition of C5a-induced human
      neutrophil migration. Clot lysis time prolongation was examined by a tissue-type
      plasminogen activator-induced clot lysis assay. RESULTS: CPB2 activity in human
      plasma was increased by TM alfa and thrombin in a concentration-dependent manner.
      TM alfa inhibited tissue factor-induced thrombin generation and enhanced pro-CPB2
      activation in human plasma simultaneously. The mass spectrum of C5a treated with
      TM alfa, thrombin, and pro-CPB2 was decreased at 156m/z, indicating that TM alfa
      enhanced the processing of C5a to C-terminal-cleaved C5a, an inactive form of
      C5a. C5a-induced human neutrophil migration was decreased after C5a treatment
      with TM alfa, thrombin, and pro-CPB2. TM alfa prolonged the clot lysis time in
      human plasma, and this effect was completely abolished by addition of a CPB2
      inhibitor. CONCLUSIONS: TM alfa exerts anti-inflammatory and anti-fibrinolytic
      effects through CPB2 in the presence of thrombin in vitro.

PMID- 27693846
TI  - Grey matter volume differences in the left caudate nucleus of people who stutter.
AB  - The cause of stuttering has many theoretical explanations. A number of research
      groups have suggested changes in the volume and/or function of the striatum as a
      causal agent. Two recent studies in children and one in adults who stutter (AWS)
      report differences in striatal volume compared that seen in controls; however,
      the laterality and nature of this anatomical volume difference is not consistent
      across studies. The current study investigated whether a reduction in striatal
      grey matter volume, comparable to that seen in children who stutter (CWS), would
      be found in AWS. Such a finding would support claims that an anatomical striatal
      anomaly plays a causal role in stuttering. We used voxel-based morphometry to
      examine the structure of the striatum in a group of AWS and compared it to that
      in a group of matched adult control subjects. Results showed a statistically
      significant group difference for the left caudate nucleus, with smaller mean
      volume in the group of AWS. The caudate nucleus, one of three main structures
      within the striatum, is thought to be critical for the planning and modulation of
      movement sequencing. The difference in striatal volume found here aligns with
      theoretical accounts of stuttering, which suggest it is a motor control disorder
      that arises from deficient articulatory movement selection and sequencing. Whilst
      the current study provides further evidence of a striatal volume difference in
      stuttering at the group level compared to controls, the significant overlap
      between AWS and controls suggests this difference is unlikely to be diagnostic of
      stuttering.

PMID- 27693847
TI  - Lentinan produces a robust antidepressant-like effect via enhancing the
      prefrontal Dectin-1/AMPA receptor signaling pathway.
AB  - Lentinan (LNT) is an immune regulator and its potential and mechanism for the
      treatment of mood disorder is of our interest. Dectin-1 is a beta-glucan
      (including LNT) receptor that regulates immune functions in many immune cell
      types. Cumulative evidence has suggested that the glutamatergic system seems to
      play an important role in the treatment of depression. Here, we studied the
      antidepressant-like effects of LNT and its therapeutical target in regulating the
      functions of AMPA receptors. We found that 60min treatment with LNT leads to a
      significant antidepressant-like effect in the tail suspension test (TST) and the
      forced swim test (FST) in mice. The antidepressant-like effects of LNT in TST and
      FST remained after 1day or 5days of injections. Additionally, LNT did not show a
      hyperactive effect in the open field test. Dectin-1 receptor levels were
      increased after LNT treatment for 5days and the specific Dectin-1 inhibitor
      laminarin was able to block the antidepressant-like effects of LNT. After 5days
      of treatment, LNT enhanced p-GluR1 (S845) in the prefrontal cortex (PFC);
      however, the total GluR1, GluR2, and GluR3 expression levels remained unchanged.
      We also found that the AMPA-specific blocker GYKI 52466 was able to block the
      antidepressant-like effects of LNT. This study identified LNT as a novel
      antidepressant with clinical potential and a new antidepressant mechanism for
      regulating prefrontal Dectin-1/AMPA receptor signaling.

PMID- 27693848
TI  - Kynurenine 3-monooxygenase is implicated in antidepressants-responsive depressive
      like behaviors and monoaminergic dysfunctions.
AB  - l-Tryptophan (TRP) is metabolized via serotonin and kynurenine pathways (KP).
      Several studies have demonstrated that abnormality of both pathways is involved
      in the pathogenesis of major depressive disorder (MDD). Kynurenine 3
      monooxygenase (KMO), a pivotal enzyme in the KP, has been suggested to play major
      roles in physiological and pathological events mediated by bioactive kynurenine
      metabolites. In this study, we investigated the role of KMO in the emotional and
      cognitive functions by using KMO knockout (KO) mice. We measured contents of TRP
      and monoamines and their metabolites in the serum and hippocampus of KMO KO mice.
      Further, we investigated whether antidepressants improved the depressive-like
      behaviors in KMO KO mice. KMO KO mice showed depressive-like behaviors such as
      decreased sucrose preference and increased immobility in the forced swimming test
      and high anxiety by decreased time spent in the center area of open field. But,
      there was no difference in spontaneous alternation in Y-maze test, counts of
      rearing or locomotor activity. Higher contents of TRP metabolites such as
      kynurenine (KYN), kynurenic acid (KA), anthranilic acid (AA), and 3
      hydroxykynurenine (3-HK) in the serum and hippocampus and decreased serotonin
      turnover and higher content of normetanephrine (NM) in the hippocampus were
      observed in the KMO KO mice. Although both antidepressant attenuated increase of
      immobility, sertraline but not imipramine improved decrease of sucrose preference
      in the KMO KO mice. These findings suggested that KMO KO mice show
      antidepressants-responsive depressive-like behaviors and monoaminergic
      dysfunctions via abnormality of kynurenine metabolism with good validities as MDD
      model.

PMID- 27693849
TI  - Searching for signs of aging and dementia in EEG through network analysis.
AB  - Graph theory applications had spread widely in understanding how human cognitive
      functions are linked to dynamics of neuronal network structure, providing a
      conceptual frame that can reduce the analytical brain complexity. This review
      summarizes methodological advances in this field. Electroencephalographic
      functional network studies in pathophysiological aging will be presented,
      focusing on neurodegenerative disease -such Alzheimer's disease-aiming to discuss
      whether network science is changing the traditional concept of brain disease and
      how network topology knowledge could help in modeling resilience and
      vulnerability of diseases. Aim of this work is to open discussion on how network
      model could better describe brain architecture.

PMID- 27693850
TI  - Selective amotivation deficits following chronic psychosocial stress in mice.
AB  - Amotivation is a major symptom of several psychiatric disorders. However, which
      specific motivations are most affected in various illnesses is not well
      understood. In major depressive disorder (MDD), anecdotal evidence suggests the
      motivation to explore may be especially affected, but direct evidence from either
      patients or animal models is lacking. To investigate the potential for, and
      nature of, exploratory drive deficits in MDD, we subjected mice to a chronic
      social defeat (CSD) manipulation that gives rise to a MDD-like behavioural
      ensemble, and performed a behavioural battery to examine bodyweight homeostasis,
      ambulation, anxiety, exploratory behaviour motivated by either novelty or fear,
      and short-term memory. Consistent with previous reports, we found a disruption of
      bodyweight homeostasis and reduced ambulation following CSD treatment, but we
      found no evidence for anxiogenic effects or impairments in short-term memory.
      Surprisingly, we also observed profoundly delayed and diminished exploration of
      novel, safe space following CSD, while exploration motivated by fear remained
      intact. These results extend our knowledge of the behavioural phenotypes in mice
      resulting from CSD by homing in on specific motivational drives. In MDD patients,
      reduced exploration could compound disease symptomatology by preventing
      engagement in what could be rewarding exploration experiences, and targeting
      deficits in the motivation to explore may represent a novel avenue for treatment.

PMID- 27693851
TI  - Behavioral facilitation after hippocampal lesion: A review.
AB  - When parts of the brain suffer from damage, certain functional deficits or
      impairments are the expected and typical outcome. A myriad of examples show such
      negative consequences, which afford the daily tasks of neurologists,
      neuropsychologists, and also behavioral neuroscientists working with experimental
      brain lesions. Compared to lesion-induced deficits, examples for functional
      enhancements or facilitation after brain lesions are rather rare and usually not
      well studied. Here, the mammalian hippocampus seems to provide an exception,
      since substantial evidence shows that its damage can have facilitatory behavioral
      effects under certain conditions. This review will address these effects and
      their possible mechanisms. It will show that facilitatory effects of hippocampal
      lesions, although mostly studied in rats, can be found in many mammalian species,
      that is, they are apparently not species-specific. Furthermore, they can be found
      with various lesion techniques, from tissue ablation, to neurotoxic damage, and
      from damage of hippocampal structure itself to damage of fiber systems
      innervating it. The major emphasis of this review, however, lies on the
      behavioral effects and their interpretations. Thus, facilitatory effects can be
      found in several learning paradigms, especially active avoidance, and some forms
      of Pavlovian and instrumental conditioning. These will be discussed in light of
      pertinent theories of hippocampal function, such as inhibition, spatial
      cognition, and multiple memory systems theories, which state that facilitatory
      effects of hippocampal lesions may reflect the loss of interference between
      hippocampal spatial and striatal procedural cognition. Using the example of the
      rat sequential reaction time task, it will also be discussed how such lesions can
      have direct and indirect consequences on certain behavioral readouts. A final
      note will advocate considering possible functional facilitation also in
      neurologic patients, especially those with hippocampal damage, since such a
      strategy might provide new avenues for therapeutic treatments.

PMID- 27693852
TI  - Chronic post-traumatic stress disorder-related traits in a rat model of low-level
      blast exposure.
AB  - The postconcussion syndrome following mild traumatic brain injuries (mTBI) has
      been regarded as a mostly benign syndrome that typically resolves in the
      immediate months following injury. However, in some individuals, symptoms become
      chronic and persistent. This has been a striking feature of the mostly blast
      related mTBIs that have been seen in veterans returning from the recent conflicts
      in Iraq and Afghanistan. In these veterans a chronic syndrome with features of
      both the postconcussion syndrome and post-traumatic stress disorder has been
      prominent. Animal modeling of blast-related TBI has developed rapidly over the
      last decade leading to advances in the understanding of blast pathophysiology.
      However, most studies have focused on acute to subacute effects of blast on the
      nervous system and have typically studied higher intensity blast exposures with
      energies more comparable to that involved in human moderate to severe TBI. Fewer
      animal studies have addressed the chronic effects of lower level blast exposures
      that are more comparable to those involved in human mTBI or subclinical blast.
      Here we describe a rat model of repetitive low-level blast exposure that induces
      a variety of anxiety and PTSD-related behavioral traits including exaggerated
      fear responses that were present when animals were tested between 28 and 35 weeks
      after the last blast exposure. These animals provide a model to study the chronic
      and persistent behavioral effects of blast including the relationship of PTSD to
      mTBI in dual diagnosis veterans.

PMID- 27693853
TI  - Melatonin and cortisol profiles in the absence of light perception.
AB  - As light plays an important role in the synchronisation of the internal
      biological clock to the environmental day/night schedule, we compared the 24-h
      profiles of biological circadian markers in blind and normal sighted individuals.
      Salivary melatonin and cortisol concentrations were collected every two hours in
      eleven blind subjects, reporting no conscious light perception, and eleven age-
      and sex-matched normal sighted controls. Timing of melatonin onset and associated
      cortisol quiescence period confirm an increased incidence of abnormal circadian
      patterns in blindness. Additionally, blind subjects showed a greater overall
      melatonin concentration throughout the 24-h period. Cortisol profiles, including
      concentration and morning cortisol peaks, on the other hand, did not differ
      between blind and sighted individuals. These findings support previous reports of
      an increase in abnormal circadian rhythms and the absence of the entrainment
      properties of light in blindness.

PMID- 27693854
TI  - The impact of trauma on the onset of mental health symptoms, aggression, and
      criminal behavior in an inpatient psychiatric sample.
AB  - Experiences of trauma and maltreatment are frequent predictors of poor physical
      and mental health outcomes in adulthood. Existing literature also suggests an
      impact of developmental adversity on criminality and aggressive behavior, though
      little research exists describing the effects of cumulative adversity in forensic
      mental health samples. In the current study of 381 forensic mental health
      inpatients, rates of trauma, neglect, and parental substance abuse are reported
      in comparison with community norms. Cumulative adversity and the occurrence of
      foster care placement are examined via linear and logistic regression analyses in
      relation to age at first arrest, first psychiatric hospitalization, and onset of
      aggression, as well as history of suicide attempts and non-suicidal self-injury.
      Results revealed that experiences of developmental adversity were more common
      among participants than have been reported in community samples using the ACE
      survey, and that there were differential effects of gender on the prevalence of
      traumas experienced. Cumulative adversity scores were significantly associated
      with all outcomes, though the addition of foster care placement to the model
      significantly contributed to understanding outcomes, and in some cases, removed
      the effect of cumulative adversity. Implications and direction for future study
      are discussed.

PMID- 27693855
TI  - TP53-induced glycolysis and apoptosis regulator protects from spontaneous
      apoptosis and predicts poor prognosis in chronic lymphocytic leukemia.
AB  - OBJECTIVES: Circulating chronic lymphocytic leukemia (CLL) cells appear not to be
      overly utilizing aerobic glycolysis. However, recurrent contact with CLL cells in
      a stromal microenvironment leads to increased aerobic glycolysis and the cells'
      overall glycolytic capacity, which promotes cell survival and proliferation. TP53
      induced glycolysis and apoptosis regulator (TIGAR) has been directly implicated
      in cellular metabolism in the control of glycolysis. TIGAR inhibits glycolysis
      and protects cells from intracellular reactive oxygen species (ROS)-associated
      apoptosis. METHODS: TIGAR mRNA expression was investigated by quantitative PCR in
      102 newly diagnosed CLL patients. Furthermore, the relationship between the
      expression of TIGAR and its clinical characteristics and prognosis were
      investigated. Moreover, we also investigated the correlation between TIGAR
      expression and apoptosis in primary CLL cells. RESULTS: Our data revealed that
      TIGAR overexpression was correlated with the protection from spontaneous
      apoptosis in CLL cells, and is strongly associated with advanced Binet stage,
      unmutated immunoglobulin heavy-chain variable region (IGHV) status, CD38
      positivity, beta2-microglobulin and p53 aberrations. Higher expression of TIGAR
      was associated with shorter treatment-free survival (median: three months vs. 51
      months, P=0.0108), worse overall survival (median: 74 months vs. not reached,
      P=0.0242), and the diverse responses to fludarabine-based chemotherapy. TIGAR
      expression in patients resistant to chemotherapy was significantly higher than in
      patients sensitive to chemotherapy (mean: 0.3859+/-0.1710 vs. 0.0974+/-0.0291,
      P=0.0290). CONCLUSION: Taken together, our findings revealed that high TIGAR
      expression is closely correlated with worse clinical outcome in CLL patients, and
      depicted how bioenergetic characteristics could be therapeutically exploited in
      CLL.

PMID- 27693856
TI  - Gradient-dependent release of the model drug TRITC-dextran from FITC-labeled BSA
      hydrogel nanocarriers in the hair follicles of porcine ear skin.
AB  - Hair follicle research is currently focused on the development of drug-loaded
      nanocarriers for the targeting of follicular structures in the treatment of skin
      and hair follicle-related disorders. In the present study, a dual-label
      nanocarrier system was implemented in which FITC-labeled BSA hydrogel
      nanocarriers loaded with the model drug and dye TRITC-dextran were applied
      topically to porcine ear skin. Follicular penetration and the distribution of
      both dyes corresponding to the nanocarriers and the model drug in the follicular
      ducts subsequent to administration to the skin were investigated using confocal
      laser scanning microscopy. The release of TRITC-dextran from the particles was
      induced by washing of the nanocarriers, which were kept in a buffer containing
      TRITC-labeled dextran to balance out the diffusion of the dextran during storage,
      thereby changing the concentration gradient. The results showed a slightly but
      statistically significantly deeper follicular penetration of fluorescent signals
      corresponding to TRITC-dextran as opposed to fluorescence corresponding to the
      FITC-labeled particles. The different localizations of the dyes in the cross
      sections of the skin samples evidenced the release of the model drug from the
      labeled nanoparticles.

PMID- 27693857
TI  - Neuroprotective mechanism of Coenzyme Q10 (CoQ10) against PTZ induced kindling
      and associated cognitive dysfunction: Possible role of microglia inhibition.
AB  - BACKGROUND: Neuroinflammation, oxidative stress and mitochondrial dysfunction
      play a significant role to explain the pathophysiology of epilepsy.
      Neuroinflammation through microglia activation has been documented in
      epileptogenesis. Compounds which inhibit activation of glial cells have been
      suggested as one of the treatment approaches for the effective treatment of
      epilepsy. The present study has been designed to investigate the role of coenzyme
      Q10 and its interaction with minocycline (microglia inhibitor) against
      pentylenetetrazol (PTZ) induced kindling epilepsy. METHODS: Laca mice received
      Coenzyme Q10 and minocycline for a period of 29 days. PTZ (40mg/kg ip) injection
      has been given on alternate days. Various behavioural parameters (kindling score
      and elevated plus maze), biochemical parameters (lipid peroxidation, superoxide
      dismutase, reduced glutathione, catalase, nitrite and acetylcholinesterase) and
      mitochondrial enzyme complex activities of (I, II and IV) were assessed in the
      discrete areas of the brain. RESULTS: Administration of a subconvulsive dose of
      PTZ (40mg/kg) repeatedly increased significantly kindling score, oxidative damage
      and impaired mitochondrial enzyme complex activities (I, II and IV) and pro
      inflammatory marker (TNF-alpha) as compared to naive animals. Coenzyme Q10 (10,
      20 and 40mg/kg) and minocycline (50 and 100mg/kg) for a duration of 29days
      significantly attenuated kindling score, reversed oxidative damage, TNF-alpha and
      restored mitochondrial enzyme complex activities (I, II and IV) as compared to
      control. Further, combinations of CoQ10 (10, 20mg/kg) with minocycline (50 and
      100mg/kg) significantly modulate the protective effect of CoQ10 which was
      significant as compared to their effect per se in PTZ treated animals.
      CONCLUSION: The present study suggests the involvement of microglia inhibition in
      the protective effect of CoQ10 in PTZ induced kindling in mice.

PMID- 27693858
TI  - Egg structure and ultrastructure of Paterdecolyus yanbarensis (Insecta,
      Orthoptera, Anostostomatidae, Anabropsinae).
AB  - The egg structure of Paterdecolyus yanbarensis was examined using light, scanning
      electron and transmission electron microscopy. The egg surface shows a distinct
      honeycomb pattern formed by exochorionic ridges. Several micropyles are clustered
      on the ventral side of the egg. The egg membrane is composed of an exochorion
      penetrated with numerous aeropyles, an endochorion, and an extremely thin
      vitelline membrane. The endochorion is thickened at the posterior egg pole,
      probably associated with water absorption. A comparison of egg structure among
      Orthoptera revealed that the micropylar distribution pattern is conserved in
      Ensifera and Caelifera and might be regarded as a groundplan feature for each
      group; in Ensifera, multiple micropyles are clustered on the ventral side of the
      egg, whereas in Caelifera, micropyles are arranged circularly around the
      posterior pole of the egg.

PMID- 27693860
TI  - New Concepts in Hypertension Management: A Population-Based Perspective.
AB  - Hypertension (HTN) is the most common chronic disease in the U.S., and the
      standard model of office-based care delivery has yielded suboptimal outcomes,
      with approximately 50% of affected patients not achieving blood pressure (BP)
      control. Poor population-level BP control has been primarily attributed to
      therapeutic inertia and low patient engagement. New models of care delivery
      utilizing patient-generated health data, comprehensive assessment of social
      health determinants, computerized algorithms generating tailored interventions,
      frequent communication and reporting, and non-physician providers organized as an
      integrated practice unit, have the potential to transform population-based HTN
      control. This review will highlight the importance of these elements and
      construct the rationale for a reengineered model of care delivery for populations
      with HTN.

PMID- 27693859
TI  - Blood cell respirometry is associated with skeletal and cardiac muscle
      bioenergetics: Implications for a minimally invasive biomarker of mitochondrial
      health.
AB  - Blood based bioenergetic profiling strategies are emerging as potential reporters
      of systemic mitochondrial function; however, the extent to which these measures
      reflect the bioenergetic capacity of other tissues is not known. The premise of
      this work is that highly metabolically active tissues, such as skeletal and
      cardiac muscle, are susceptible to differences in systemic bioenergetic capacity.
      Therefore, we tested whether the respiratory capacity of blood cells, monocytes
      and platelets, are related to contemporaneous respirometric assessments of
      skeletal and cardiac muscle mitochondria. 18 female vervet/African green monkeys
      (Chlorocebus aethiops sabaeus) of varying age and metabolic status were examined
      for this study. Monocyte and platelet maximal capacity correlated with maximal
      oxidative phosphorylation capacity of permeabilized skeletal muscle (R=0.75, 95%
      confidence interval [CI]: 0.38-0.97; R=0.51, 95%CI: 0.05-0.81; respectively),
      isolated skeletal muscle mitochondrial respiratory control ratio (RCR; R=0.70,
      95%CI: 0.35-0.89; R=0.64, 95%CI: 0.23-0.98; respectively), and isolated cardiac
      muscle mitochondrial RCR (R=0.55, 95%CI: 0.22-0.86; R=0.58, 95%CI: 0.22-0.85;
      respectively). These results suggest that blood based bioenergetic profiling may
      be used to report on the bioenergetic capacity of muscle tissues. Blood cell
      respirometry represents an attractive alternative to tissue based assessments of
      mitochondrial function in human studies based on ease of access and the minimal
      participant burden required by these measures.

PMID- 27693861
TI  - Hypertension Treatment in Blacks: Discussion of the U.S. Clinical Practice
      Guidelines.
AB  - Blacks are especially susceptible to hypertension (HTN) and its associated organ
      damage leading to adverse cardiovascular, cerebrovascular and renal outcomes.
      Accordingly, HTN is particularly significant in contributing to the black-white
      racial differences in health outcomes in the US. As such, in order to address
      these health disparities, practical clinical practice guidelines (CPGs) on how to
      treat HTN, specifically in blacks, are needed. This review article is a timely
      addition to the literature because the most recent U.S. CPG more explicitly
      emphasizes race into the algorithmic management of HTN. However, recent clinical
      research cautions that use of race as a proxy to determine therapeutic response
      to pharmaceutical agents may be erroneous. This review will address the
      implications of the use of race in the hypertension CPGs. We will review the
      rationale behind the introduction of race into the U.S. CPG and the level of
      evidence that was available to justify this introduction. Finally, we will
      conclude with practical considerations in the treatment of HTN in blacks.

PMID- 27693862
TI  - How do the definitions of urban and rural matter for transportation safety? Re
      interpreting transportation fatalities as an outcome of regional development
      processes.
AB  - Urban and rural places are integrated through economic ties and population flows.
      Despite their integration, most studies of road safety dichotomize urban and
      rural places, and studies have consistently demonstrated that rural places are
      more dangerous for motorists than urban places. Our study investigates whether
      these findings are sensitive to the definition of urban and rural. We use three
      different definitions of urban-rural continua to quantify and compare motor
      vehicle occupant fatality rates per person-trip and person-mile for the state of
      Wisconsin. The three urban-rural continua are defined by: (1) popular impressions
      of urban, suburban, and rural places using a system from regional economics; (2)
      population density; and (3) the intensity of commute flows to core urbanized
      areas. In this analysis, the three definitions captured different people and
      places within each continuum level, highlighting rural heterogeneity. Despite
      this heterogeneity, the three definitions resulted in similar fatality rate
      gradients, suggesting a potentially latent "rural" characteristic. We then used
      field observations of urban-rural transects to refine the definitions. When
      accounting for the presence of higher-density towns and villages in rural places,
      we found that low-density urban places such as suburbs and exurbs have fatality
      rates more similar to those in rural places. These findings support the need to
      understand road safety within the context of regional development processes
      instead of urban-rural categories.

PMID- 27693865
TI  - Help-seeking behaviors and mental well-being of first year undergraduate
      university students.
AB  - University students demonstrate poor help-seeking behatabviors for their mental
      health, despite often reporting low levels of mental well-being. The aims of this
      study were to examine the help-seeking intentions and experiences of first year
      university students in terms of their mental well-betabing, and to extaplore
      these students' views on formal (e.g. psychiatrists) and informal (e.g. friends)
      help-seeking. Students from a universitytab in the Republic of Ireland (n=220)
      completed an online questionnaire which focused on mental well-being and help
      seeking behaviors. Almost a third of students had sought help from a mental
      health professional. Very few students reported availing of university/online
      supports. Informal sources of help were more popular than formal sources, and
      those who would avail and had availed of informal sources demonstrated higher
      well-being scores. Counselors were the source of professional help most widely
      used. General practitioners, chaplains, social workers, and family therapists
      were rated the most helpful. Those with low/average well-being scores were less
      likely to seek help than those with higher scores. Findings indicate the
      importance of enhancing public knowledge of mental health issues, and for further
      examination of students' knowledge of help-seeking resources in order to improve
      the help-seeking behaviors and mental well-being of this population group.

PMID- 27693864
TI  - Acanthamoeba and Dictyostelium Use Different Foraging Strategies.
AB  - Amoeba often use cell movement as a mechanism to find food, such as bacteria, in
      their environment. The chemotactic movement of the soil amoeba Dictyostelium to
      folate or other pterin compounds released by bacteria is a well-documented
      foraging mechanism. Acanthamoeba can also feed on bacteria but relatively little
      is known about the mechanism(s) by which this amoeba locates bacteria.
      Acanthamoeba movement in the presence of folate or bacteria was analyzed in above
      agar assays and compared to that observed for Dictyostelium. The overall mobility
      of Acanthamoeba was robust like that of Dictyostelium but Acanthamoeba did not
      display a chemotactic response to folate. In the presence of bacteria,
      Acanthamoeba only showed a marginal bias in directed movement whereas
      Dictyostelium displayed a strong chemotactic response. A comparison of genomes
      revealed that Acanthamoeba and Dictyostelium share some similarities in G protein
      signaling components but that specific G proteins used in Dictyostelium
      chemotactic responses were not present in current Acanthamoeba genome sequence
      data. The results of this study suggest that Acanthamoeba does not use chemotaxis
      as the primary mechanism to find bacterial food sources and that the chemotactic
      responses of Dictyostelium to bacteria may have co-evolved with chemotactic
      responses that facilitate multicellular development.

PMID- 27693863
TI  - Host response to Clostridium difficile infection: Diagnostics and detection.
AB  - Clostridium difficile infection (CDI) is a significant healthcare concern
      worldwide, and C. difficile is recognised as the most frequent aetiological agent
      of infectious healthcare-associated diarrhoea in hospitalised adult patients. The
      clinical manifestation of CDI varies from self-limited diarrhoea to life
      threatening colitis. Such a broad disease spectrum can be explained by the impact
      of host factors. Currently, a complex CDI aetiology is widely accepted,
      acknowledging the interaction between bacteria and the host. C. difficile strains
      producing clostridial toxins A and B are considered toxigenic and can cause
      disease; those not producing the toxins are non-pathogenic. A person colonised
      with a toxigenic strain will not necessarily develop CDI. It is imperative to
      recognise patients with active disease from those only colonised with this
      pathogen and to implement appropriate treatment. This can be achieved by
      diagnostics that rely on host factors specific to CDI. This review will focus on
      major aspects of CDI pathogenesis and molecular mechanisms, describing host
      factors in disease progression and assessment of the host response in order to
      facilitate the development of CDI-specific diagnostics.

PMID- 27693866
TI  - Demographic and clinical characteristics of current comorbid psychiatric
      disorders in a randomized clinical trial for adults with stimulant use disorders.
AB  - This study aimed to determine if current comorbid psychiatric disorders differ in
      adults with cocaine use disorder, other stimulant (primarily methamphetamine) use
      disorder, or both, and identify demographic and clinical characteristics in those
      with increasing numbers of comorbid disorders. Baseline data from a randomized
      controlled trial beginning in residential settings (N=302) was used. Mood
      disorders were present in 33.6%, and anxiety disorders in 29.6%, with no
      differences among stimulant use disorder groups. Panic disorder was more
      frequently present with other stimulant use disorder. Those with two or more
      comorbid psychiatric disorders were more often female, White, had more symptoms
      of depression, greater propensity and risk for suicidal behavior, lower
      functioning in psychiatric and family domains, lower quality of life, more
      symptoms with stimulant abstinence and greater likelihood of marijuana
      dependence. Those with one or more comorbid disorders had more medical disorder
      burden, lower cognitive and physical functioning, greater pain, and higher rates
      of other drug dependence. With current comorbid psychiatric disorders, the
      morbidity of stimulant use disorders increases. Use of validated assessments near
      treatment entry, and a treatment plan targeting not only substance use and
      comorbid psychiatric disorders, but functional impairments, medical disorder
      burden and pain, may be useful.

PMID- 27693867
TI  - Patterns of antipsychotics' prescription in Portuguese acute psychiatric wards: A
      cross-sectional study.
AB  - This study aimed to establish the prescribing patterns of antipsychotics in acute
      psychiatric wards across Portugal, to determine the prevalence of polypharmacy
      and "high-doses" treatment, and to identify possible predictors. Twelve acute
      psychiatric inpatient units and 272 patients were included. The majority (87.5%)
      was treated with antipsychotics regardless of diagnosis, and 41.6% had at least
      two antipsychotics prescribed in combination. Age, use of depot antipsychotics,
      and antipsychotic "high-doses" were significant predictors of antipsychotic
      polypharmacy. Excluding 'as required' prescriptions, 13.8% of the patients were
      prescribed "high-doses" of antipsychotics. When antipsychotics 'as required'
      prescriptions were considered, 49.2% of the patients were on antipsychotic "high
      doses". Age, use of depot antipsychotics, previous psychiatric hospitalization
      and involuntary admission were significant predictors of antipsychotic "high
      doses". These results show that in Portugal the antipsychotics prescribing
      practices in psychiatric inpatient units diverge from those that are universally
      recommended, entailing important clinical and economic implications. It seems
      advisable to optimize the prescription of these drugs, in order to prevent
      adverse effects and improve the quality of the services provided.

PMID- 27693868
TI  - Ilizarov bone transport after massive tibial trauma: Case report.
AB  - INTRODUCTION: This is a case report of extreme lengthening of the tibia of about
      14.5cm using bone transport technique following road traffic accident trauma to
      the lower limbs. The management of the subsequent massive skeletal defects was
      challenging to orthopedic surgeons. Based on reported cases, the highest tibial
      lengthening was 22cm using bifocal transport, while the highest unifocal tibial
      lengthening reached 14.5cm. CASE PRESENTATION: A 20-year-old male driver was
      brought to the emergency department after a road traffic accident. The patient
      had a right Gustilo IIIA segmental open tibia fracture with bone loss and other
      severe injuries. The tibial defect was 14.5cm and the patient was then admitted
      for Ilizarov application six months after the accident. Although this case was
      particularly complicated, full limb length was restored. DISCUSSION: The
      management of this case was directed to correct the deformities and achieve equal
      length of both limbs to restore the normal function. Several new techniques have
      been developed recently to fill large bone defects. Limb lengthening using bone
      transport technique by application of Ilizarov ring fixator has been suggested as
      the leading option in filling massive bone gaps. CONCLUSION: The use of bone
      transport technique using Ilizarov external rings has proved to be a minimally
      invasive and reliable method in managing massive bone defects. Accurate
      application of the Ilizarov frame and proper transport of the middle segment are
      important factors alleviating the risk for deviation of the transported segment.
      However, due to the need for regular follow-ups and monitoring, it demands high
      compliance from the patient to achieve optimal results.

PMID- 27693869
TI  - Colo-colonic intussusception due to large submucous lipoma: A case report.
AB  - INTRODUCTION: Intussusception in adult is rarely caused by idiopathic conditions.
      Main causes are inflammatory diseases, benign or malignant tumors and motility
      disorders. As a benign cause, lipomas appear as a particularly rare
      gastrointestinal intraluminal tumor occurring with highest incidence in the
      colon, mostly in the caecum and ascending colon. PRESENTATION OF CASE: A 57-year
      old male patient was admitted at the surgical emergency in Belo Horizonte, with
      history of chronic and intermittent diffuse abdominal pain, associated with
      variations of his bowel habits and rare episodes of vomiting starting around
      3days prior to admission. DISCUSSION: Intussusception is the cause of adult
      symptomatic bowel obstruction in 1% of the cases and its colocolonic occurrence
      represents 17% of all intestinal intussusceptions in adults. The reported case
      presents itself as even rarer considering its evaluation according to the
      epidemiological statistics of 1:5 men/women ratio and lipoma's most common
      location being the right colon. Intussusception and intestinal obstructions
      caused by intraluminal lipomas are not often described in the literature and its
      occurrence is directly related to its size, usually larger than 2cm diameter. The
      management of lipomatous intraluminal lesions of the colon is traditionally
      surgical, and it allows a selective resection, depending on the size of the
      tumor, length of intussusception, and the amount of inflammation. CONCLUSION:
      Patients with chronic abdominal symptoms and semi-obstruction caused by
      intussusception are rarely diagnosed before surgery unless there is a high index
      of suspicion. Colonoscopy contributes to diagnosis given that it provides direct
      visualization and biopsy.

PMID- 27693870
TI  - Primary bacterial peritonitis in a previously healthy adolescent female: A case
      report.
AB  - INTRODUCTION: Acute pneumococcal peritonitis represents an unusual entity
      characterized by infection in the abdominal cavity despite the absence of an
      obvious causative source. Patients with portal hypertension such as cirrhotics
      and those with nefrotic syndrome are more frequently encountered in the every day
      practice. PRESENTATION OF CASE: A 14 years old female was referred to our
      department by his general practitioner with a 24h history of right lower
      abdominal pain and fever. Clinical examination was suggestive for peritonitis and
      the girl was transferred to the operation room. A diagnosis of primary
      pneumococcal peritonitis was made on the basis of the findings during surgery and
      the microbiological tests. Institution of appropriate antibiotics resulted to
      complete recovery. DISCUSSION: A mini literature review was performed.
      CONCLUSION: Primary bacterial peritonitis in adolescents is extremely rare.
      Surgeons are required to be aware of this entity.

PMID- 27693871
TI  - Supratherapeutic anti-factor Xa levels in patients receiving prophylactic doses
      of enoxaparin: A case series.
AB  - INTRODUCTION: Enoxaparin prophylaxis prevents venous thromboembolism in surgical
      patients. Real time anti-Factor Xa monitoring for surgical patients on enoxaparin
      prophylaxis is increasingly common. PRESENTATION OF CASES: We report on three
      cancer patients with therapeutic or supratherapeutic anti-Factor Xa levels while
      on prophylactic doses of enoxaparin after surgical procedures. In all cases,
      elevated anti-Factor Xa levels were the result of blood specimens being removed
      from a heparinized chemoport. DISCUSSION: This case series highlights the
      importance of peripheral venipuncture or appropriate blood wasting from central
      access sites for anti-Factor Xa levels. CONCLUSION: Inappropriately drawn anti
      Factor Xa levels may contribute to prophylaxis interruption or unnecessary workup
      for renal or liver failure.

PMID- 27693872
TI  - A highly efficient immobilized ZnO/Zn photoanode for degradation of azo dye
      Reactive Green 19 in a photocatalytic fuel cell.
AB  - Photocatalytic fuel cell (PFC) is a potential wastewater treatment technology
      that can generate electricity from the conversion of chemical energy of organic
      pollutants. An immobilized ZnO/Zn fabricated by sonication and heat attachment
      method was applied as the photoanode and Pt/C plate was used as the cathode of
      the PFC in this study. Factors that affect the decolorization efficiency and
      electricity generation of the PFC such as different initial dye concentrations
      and pH were investigated. Results revealed that the degradation of Reactive Green
      19 (RG19) was enhanced in a closed circuit PFC compared with that of a opened
      circuit PFC. Almost 100% decolorization could be achieved in 8 h when 250 mL of
      30 mg L-1 of RG19 was treated in a PFC without any supporting electrolyte. The
      highest short circuit current of 0.0427 mA cm-2 and maximum power density of
      0.0102 mW cm-2 was obtained by PFC using 30 mg L-1 of RG19. The correlation
      between dye degradation, conductivity and voltage output were also investigated
      and discussed.

PMID- 27693873
TI  - Formation and speciation of haloacetamides and haloacetonitriles for
      chlorination, chloramination, and chlorination followed by chloramination.
AB  - The formation of haloacetamides (HAcAms) and haloacetonitriles (HANs) from a
      solution containing natural organic matter and a secondary effluent sample was
      evaluated for disinfection by chlorination, chloramination, and chlorination
      followed by chloramination (Cl2NH2Cl process). The use of preformed
      monochloramine (NH2Cl) produced higher concentrations of HAcAms and lower
      concentrations of HANs than chlorination, while the Cl2NH2Cl process produced the
      highest concentrations of HAcAms and HANs. These results indicate that the
      Cl2NH2Cl process, which inhibited the formation of regulated trihalomethanes
      compared with chlorination, enhanced the formation of HAcAms and HANs. For
      disinfection in the presence of bromide, brominated dihaloacetamides and
      dihaloacetonitriles were formed, and the trends were similar to those observed
      for chlorinated species in the absence of bromide. The degrees of bromine
      substitution of dihaloacetamides and dihaloacetonitriles were highest for
      chlorination, followed by the Cl2NH2Cl process and then by the NH2Cl process. For
      the Cl2NH2Cl process, HAN formation kept gradually increasing with
      prechlorination time increasing from 0 to 120 min, while HAcAm formation
      increased only until it reached a maximum at around 10-30 min. These results
      suggest that the prechlorination time could be reduced to control the formation
      of HAcAms and HANs. During chloramination, the formation of HAcAms and HANs was
      lower when using preformed NH2Cl than when chloramines were formed in situ, with
      higher formation of HAcAms and HANs when chlorine was added before ammonia than
      vice versa for the secondary effluent; this finding suggests that preformed NH2Cl
      could be used to inhibit the formation of HAcAms and HANs during chloramination.

PMID- 27693874
TI  - A study of trace element contamination using multivariate statistical techniques
      and health risk assessment in groundwater of Chhaprola Industrial Area, Gautam
      Buddha Nagar, Uttar Pradesh, India.
AB  - This study is an investigation on spatio-chemical, contamination sources (using
      multivariate statistics), and health risk assessment arising from the consumption
      of groundwater contaminated with trace and toxic elements in the Chhaprola
      Industrial Area, Gautam Buddha Nagar, Uttar Pradesh, India. In this study 33
      tubewell water samples were analyzed for 28 elements using ICP-OES. Concentration
      of some trace and toxic elements such as Al, As, B, Cd, Cr, Mn, Pb and U exceeded
      their corresponding WHO (2011) guidelines and BIS (2012) standards while the
      other analyzed elements remain below than those values. Background gamma and beta
      radiation levels were observed and found to be within their acceptable limits.
      Multivariate statistics PCA (explains 82.07 cumulative percent for total 6 of
      factors) and CA indicated (mixed origin) that natural and anthropogenic
      activities like industrial effluent and agricultural runoff are responsible for
      the degrading of groundwater quality in the research area. In this study area, an
      adult consumes 3.0 L (median value) of water therefore consuming 39, 1.94, 1461,
      0.14, 11.1, 292.6, 13.6, 23.5 MUg of Al, As, B, Cd, Cr, Mn, Pb and U from
      drinking water per day respectively. The hazard quotient (HQ) value exceeded the
      safe limit of 1 which for As, B, Al, Cr, Mn, Cd, Pb and U at few locations while
      hazard index (HI) > 5 was observed in about 30% of the samples which indicated
      potential health risk from these tubewells for the local population if the
      groundwater is consumed.

PMID- 27693875
TI  - Prussian blue analogue derived magnetic carbon/cobalt/iron nanocomposite as an
      efficient and recyclable catalyst for activation of peroxymonosulfate.
AB  - A Prussian blue analogue, cobalt hexacyanoferrate Co3[Fe(CN)6]2, was used for the
      first time to prepare a magnetic carbon/cobalt/iron (MCCI) nanocomposite via one
      step carbonization of Co3[Fe(CN)6]2. The resulting MCCI consisted of evenly
      distributed cobalt and cobalt ferrite in a porous carbonaceous matrix, making it
      an attractive magnetic heterogeneous catalyst for activating peroxymonosulfate
      (PMS). As Rhodamine B (RhB) degradation was adopted as a model test for
      evaluating activation capability of MCCI, factors influencing RhB degradation
      were thoroughly examined, including MCCI and PMS dosages, temperature, pH, salt
      and radical scavengers. A higher MCCI dosage noticeably facilitated the
      degradation kinetics, whereas insufficient PMS dosage led to ineffective
      degradation. RhB degradation by MCCI-activated PMS was much more favorable at
      high temperatures and under neutral conditions. The presence of high
      concentration of salt slightly interfered with RhB degradation by MCCI-activated
      PMS. Through examining effects of radical scavengers, RhB degradation by MCCI
      activated PMS can be primarily attributed to sulfate radicals instead of a
      combination of sulfate and hydroxyl radicals. Compared to Co3O4, a typical
      catalyst for PMS activation, MCCI also exhibited a higher catalytic activity for
      activating PMS. In addition, MCCI was proven as a durable and recyclable catalyst
      for activating PMS over multiple cycles without efficiency loss and significant
      changes of chemical characteristics. These features demonstrate that MCCI, simply
      prepared from a one-step carbonization of Co3[Fe(CN)6]2 is a promising
      heterogeneous catalyst for activating PMS to degrade organic pollutants.

PMID- 27693877
TI  - Interiliac Ureter: A Rare Venous Anomaly Causing Hydronephrosis.
AB  - Most of the developmental anomalies of inferior vena cava are asymptomatic. The
      retrocaval and retroiliac ureter, however, commonly present with symptoms due to
      ureteric obstruction. We present interesting computed tomography images of a 30
      year-old male who was symptomatic for right upper ureteric obstruction and the
      ureter was coursing between the 2 common iliac veins that were uniting abnormally
      high at the level of right renal hilum with absence of infrarenal inferior vena
      cava.

PMID- 27693876
TI  - Button Cystostomy: Is it Really a Safe and Effective Therapeutic Option in
      Pediatric Patients With Neurogenic Bladder?
AB  - OBJECTIVE: To define safety and effectiveness of cystostomy button in the
      management of bladder drainage in pediatric patients with neurogenic bladder, and
      report our personalized surgical technique. MATERIALS AND METHODS: This study is
      a retrospective analysis of patients undergoing cystostomy button placement for
      bladder drainage from October 2009 to December 2015. Endoscopic and open surgical
      techniques and medium-term complication were analyzed and indications were
      recorded. RESULTS: Thirty-five patients, 16 (45.7%) females and 19 (54.3%) males,
      underwent cystostomy button placement for bladder drainage with a mean age of 8.6
      +/- 4.8 years (standard deviation) and a mean follow-up time of 37 months. There
      were 91.4% of patients who had a neurogenic bladder; a nonobstructive urinary
      retention was diagnosed in the remainder of cases. A medium-term complication was
      mostly represented by urinary tract infection observed in 10 of 35 patients that
      was the most representative cause of button removal (4 of 35). Other observed
      complications were button leakage (n = 2), decubitus (n = 1), and bladder stone
      (n = 1). No postoperative complication was observed and no differences were found
      in terms of complications in the two surgical approaches performed. CONCLUSION:
      Cystostomy button is a safe and effective treatment for bladder drainage in
      neurogenic pediatric patients and it is also well accepted by patients and
      caregivers. Cystostomy button, which may avoid mechanical concerns and most of
      the social discomfort, should be considered an alternative method to other
      bladder drainage modalities.

PMID- 27693878
TI  - Dietary Inflammatory Index and Risk of Bladder Cancer in a Large Italian Case
      control Study.
AB  - OBJECTIVE: To evaluate the association between diet in relation to its
      inflammatory property and bladder cancer (BC) risk. METHODS: In this study we
      explored the association between the dietary inflammatory index (DII) and BC risk
      in an Italian case-control study conducted between 2003 and 2014. Cases were 690
      patients with incident and histologically confirmed BC from 4 areas in Italy.
      Controls were 665 cancer-free subjects admitted to the same network of hospitals
      as cases for a wide spectrum of acute, non-neoplastic conditions. The DII was
      computed based on dietary intake assessed using a reproducible and valid 80-item
      food frequency questionnaire. Odds ratios (OR) were estimated through logistic
      regression models adjusting for age, sex, total energy intake, and other
      recognized confounding factors. RESULTS: Subjects in the highest quartile of DII
      scores (ie, with a more pro-inflammatory diet) had a higher risk of BC compared
      to subjects in the lowest quartile (ie, with an anti-inflammatory diet)
      (ORQuartile4vs1 = 1.97; 95% [confidence interval], 1.28, 3.03; P trend = .003).
      Stratified analyses produced stronger associations between DII and BC risk among
      females (ORQuartile4vs1 = 5.73; 95% CI = 1.46, 22.44), older >=65 years
      (ORQuartile4vs1 = 2.45; 95% CI = 1.38, 4.34), subjects with higher education >=7
      years (ORQuartile4vs1 = 2.22; 95% CI = 1.27, 3.88), and never smokers
      (ORQuartile4vs1 = 4.04; 95% CI = 1.51, 10.80). CONCLUSION: A pro-inflammatory
      diet as indicated by higher DII scores is associated with increased BC risk.

PMID- 27693880
TI  - Qualitative and quantitative analysis of PMN/T-cell interactions by InFlow and
      super-resolution microscopy.
AB  - Neutrophils or polymorphonuclear cells (PMN) eliminate bacteria via phagocytosis
      and/or NETosis. Apart from these conventional roles, PMN also have immune
      regulatory functions. They can transdifferentiate and upregulate MHCII as well as
      ligands for costimulatory receptors which enables them to behave as antigen
      presenting cells (APC). The initial step for activating T-cells is the formation
      of an immune synapse between T-cells and antigen-presenting cells. However, the
      immune synapse that develops at the PMN/T-cell contact zone is as yet hardly
      investigated due to the non-availability of methods for analysis of large number
      of PMN interactions. In order to overcome these obstacles, we introduce here a
      workflow to analyse the immune synapse of primary human PMN and T-cells using
      multispectral imaging flow cytometry (InFlow microscopy) and super-resolution
      microscopy. For that purpose, we used CD3 and CD66b as the lineage markers for T
      cells and PMN, respectively. Thereafter, we applied and critically discussed
      various "masks" for identification of T-cell PMN interactions. Using this
      approach, we found that a small fraction of transdifferentiated PMN
      (CD66b+CD86high) formed stable PMN/T-cell conjugates. Interestingly, while both
      CD3 and CD66b accumulation in the immune synapse was dependent on the maturation
      state of the PMN, only CD3 accumulation was greatly enhanced by the presence of
      superantigen. The actin cytoskeleton was weakly rearranged at the PMN side on the
      immune synapse upon contact with a T-cell in the presence of superantigen. A more
      detailed analysis using super-resolution microscopy (structured-illumination
      microscopy, SIM) confirmed this finding. Together, we present an InFlow
      microscopy based approach for the large scale analysis of PMN/T-cell interactions
      and - combined with SIM - a possibility for an in-depth analysis of protein
      translocation at the site of interactions.

PMID- 27693879
TI  - Serum from obstructive sleep apnea patients induces inflammatory responses in
      coronary artery endothelial cells.
AB  - BACKGROUND AND AIMS: Obstructive sleep apnea (OSA) is characterized by
      intermittent airway obstruction and systemic hypoxia during sleep, which can
      contribute to an increase in reactive oxygen species, vascular remodeling,
      vasoconstriction and ultimately cardiovascular disease. Continuous positive
      airway pressure (CPAP) is a clinical therapy that maintains airway patency and
      mitigates several symptoms of OSA. However, it is currently unknown whether CPAP
      therapy also reduces the overall inflammatory potential in the circulation; to
      address this in an unbiased manner, we applied a novel endothelial biosensor
      approach, the serum cumulative inflammatory potential (SCIP) assay. METHODS: We
      studied healthy controls (n = 7), OSA subjects receiving no treatment, (OSA
      controls) (n = 7) and OSA subjects receiving CPAP for 3 months (n = 8). Serum was
      obtained from OSA subjects before and after CPAP or no treatment. A battery of
      quantitative and functional assays was performed to assess the serum inflammatory
      potential, in terms of endothelial responses. For the SCIP assay, human coronary
      artery endothelial cells (hCAECs) were incubated with 5% serum in media from
      individual subjects for 4 h. qPCR was performed to assess endothelial
      inflammatory transcript (ICAM-1, VCAM-1, IL-8, P-selectin, CCL5, and CXCL12)
      responses to serum. Additionally, transendothelial resistance was measured in
      serum-incubated hCAECs following leukocyte challenge. RESULTS: hCAECs exhibited
      significant increases in VCAM-1, ICAM-1, IL-8 and P-selectin mRNA when incubated
      with serum from OSA patients compared to serum from healthy control subjects.
      Furthermore, compared to no treatment, serum from CPAP-treated individuals was
      less potent at inducing inflammatory gene expression in the SCIP assay.
      Similarly, in a leukocyte adhesion assay, naive cells treated with serum from
      patients who received CPAP exhibited improved endothelial barrier function than
      cells treated with OSA control serum. CONCLUSIONS: OSA results in greater serum
      inflammatory potential, thereby driving endothelial activation and dysfunction.

PMID- 27693881
TI  - Mechanistic study of base-pairing small regulatory RNAs in bacteria.
AB  - In all three kingdoms of life, RNA is not only involved in the expression of
      genetic information, but also carries out extremely diverse cellular functions.
      This versatility is essentially due to the fact that RNA molecules can exploit
      the power of base pairing to allow them to fold into a wide variety of structures
      through which they can perform diverse roles, but also to selectively target and
      bind to other nucleic acids. This is true in particular for bacterial small
      regulatory RNAs that act by imperfect base-pairing with target mRNAs, and thereby
      control their expression through different mechanisms. Here we outline an
      overview of in vivo and in vitro approaches that are currently used to gain
      mechanistic insights into how these sRNAs control gene expression in bacteria.

PMID- 27693882
TI  - Aromatase deficiency in a male patient - Case report and review of the
      literature.
AB  - OBJECTIVE: Aromatase, or CYP19A1, is a type II cytochrome CYP450 enzyme that
      catalyzes the conversion of C19 androgens to C18 estrogens. Its crucial role in
      both female and male physiology has been deduced from human and animal studies
      using aromatase inhibitors, genetically altered mice, and patients with aromatase
      deficiency. The latter is an extremely rare disorder. Its diagnosis is
      particularly difficult in males, who go through puberty normally and therefore
      usually present as adults with elevated testosterone, bone abnormalities (e.g.,
      delayed bone age and low bone mass), and metabolic syndrome. In this report, we
      describe a new case of a male patient with aromatase deficiency harboring a known
      mutation who presented with less severe clinical and biochemical features. CASE
      REPORT: The patient presented with low bone mass and delayed bone age after a
      finger fracture at age 25years. FSH, LH and testosterone levels were normal, but
      estradiol and estrone levels were absent or barely detectable, raising suspicion
      for aromatase deficiency. A homozygous c.628G>A mutation in exon 5 was confirmed
      by direct sequencing. Unlike previously reported cases of aromatase deficiency,
      he did not display biochemical features of insulin resistance, dyslipidemia, or
      overweight/obese status. Therapy with estradiol led to the closure of growth
      plates and a dramatic increase in bone mass. CONCLUSIONS: Here we explore
      genotype/phenotype associations of this new case compared to cases reported
      previously. We conclude that the specific nature of mutation c.628G>A, which can
      potentially result in several different forms of the aromatase enzyme, may lend
      an explanation to the variable phenotypes associated with this particular
      genotype.

PMID- 27693883
TI  - Equity issues were not fully addressed in Cochrane human immunodeficiency virus
      systematic reviews.
AB  - OBJECTIVE: To describe and summarize equity reporting in human immunodeficiency
      virus (HIV) systematic reviews and explore the extent to which equity issues are
      addressed and reported in HIV reviews using the PROGRESS Plus framework. STUDY
      DESIGN AND SETTING: Application of the PROGRESS Plus framework to a bibliometric
      analysis of HIV reviews in the Cochrane Database of Systematic Reviews. RESULTS:
      The analysis included 103 reviews published as of March 2014, with a median of
      five studies per review (first quartile; Q1 = 2; third quartile; Q3 = 11).
      Reporting of PROGRESS Plus factors was as follows: Place of residence (low,
      middle, and high income; 55.3%), place of residence (urban or rural; 24.3%), race
      or ethnicity (20.4%), occupation (10.7%), gender (65.0%), religion (1.9%),
      education (7.8%), socioeconomic position (10.7%), social networks and capital
      (1.0%), age (1.9%), and sexual orientation (3.8%). CONCLUSION: Gaps in the
      reporting of relevant equity indicators were identified within Cochrane HIV
      systematic review indicating that research is not consistently conducted through
      an equity lens. There is a need to incorporate PROGRESS Plus factors into both
      primary and secondary studies.

PMID- 27693884
TI  - Time-frequency analysis of intracranial EEG in patients with myoclonic seizures.
AB  - Myoclonic seizures are defined as generalized seizures according to the
      classification of seizure by the International League Against Epilepsy (ILAE).
      The pathogenesis of myoclonic seizures is not yet clear. There are very few
      studies on the focal surgical treatment of myoclonic seizures. The aim of this
      study is to investigate the characteristics of myoclonic seizure onset in
      different bands of the intracranial electroencephalogram (EEG) and their dynamic
      changes in temporal and spatial evolution. We studied four patients with
      myoclonic seizures who were under the focal resection of the epileptogenic zone.
      We retrospectively analyzed the semiology, electrocorticogram (ECoG) and imaging
      data of these patients, and conducted time-frequency analysis of broadband ECoG
      activity. We found that myoclonic seizures without clinical lateralizing signs
      could be improved by the resection of the epileptogenic zone. The ECoG power in
      different frequency bands increased to a peak at 0.5s before the clinical seizure
      onset and decreased quickly afterwards. The power of alpha activity was highest
      during the preictal and ictal periods. The central zone had higher power than the
      epileptogenic zone in all frequency bands during the preictal period, but this
      difference was not statistically significant. Our results suggest that myoclonic
      seizures in some patients might have a focal origination, with a fast bilateral
      propagating network in all frequency bands, especially the alpha band.

PMID- 27693885
TI  - Distinct electroencephalographic responses to disturbances and distractors during
      continuous reaching movements.
AB  - Discrepancies between actual and appropriate motor commands, dubbed low-level
      errors, have been shown to elicit a P300 like component. P300 has been studied
      extensively in cognitive tasks using, in particular, the three-stimulus oddball
      paradigm. This paradigm revealed two sub-components, known as P3a and P3b, whose
      relative contributions depend on saliency and task-relevance, respectively.
      However, the existence and roles of these sub-components in response to low-level
      errors are poorly understood. Here we investigated responses to low level errors
      generated by disturbances - including target and cursor jumps, versus responses
      to distractors, i.e., environmental changes that are irrelevant to the reaching
      task. Additionally, we examined the response to matching cursor and target jumps
      (dual jumps), which generate estimation errors, and are thus considered task
      relevant disturbances, but do not generate low level errors. We found that a
      significant P3a-like component is evoked by both disturbances and distractors,
      whereas the P3b-like component is significantly stronger in response to
      disturbances than distractors. The P3b-like component appears also in response to
      dual jumps, even though there are no low level errors. We conclude that
      disturbances and distractors elicit distinct responses, and that the P3b-like
      component reflects estimation errors rather than low-level errors.

PMID- 27693886
TI  - Bipolar I disorder with comorbid PTSD: Demographic and clinical correlates in a
      sample of hospitalized patients.
AB  - BACKGROUND: According to data from epidemiological and clinical samples, there
      are elevated rates of posttraumatic stress disorder (PTSD) among patients with
      bipolar disorder (BD). However, little is known about the clinical correlates
      that may distinguish patients with BD and comorbid PTSD from those without
      comorbid PTSD. The present study sought to elucidate those differences and
      examine factors, such as psychosis, history of suicide attempts, and comorbid
      personality disorders, which may predict comorbid PTSD in patients with BD-I.
      METHODS: We conducted a retrospective chart review of 230 psychiatric inpatients
      with BD-I. RESULTS: Patients with BD-I and comorbid PTSD were significantly more
      likely to be female, to be depressed (vs. manic), to have a comorbid personality
      disorder, and to have a history of suicide attempt. Also, BD-I patients with PTSD
      were significantly less likely to present for their inpatient hospital stay with
      psychosis. These effects remained significant after controlling for mood episode
      polarity, suggesting that findings were not fully explained by the higher
      incidence of depression in the comorbid PTSD group. CONCLUSIONS: Patients with BD
      I and comorbid PTSD appear to be a high risk population with need for enhanced
      monitoring of suicidality. Clinical implications of these findings are discussed.

PMID- 27693887
TI  - Intimate partner violence is associated with increased maternal hair cortisol in
      mother-child dyads.
AB  - BACKGROUND: The chronic consequences of intimate partner violence (IPV) on HPA
      activation are a topic of debate. The current study investigated hair cortisol
      concentrations in female victims of IPV and their children. METHODS: A total of
      52 mother-child dyads were divided into two groups depending on exposure to IPV:
      IPV group (n=27 dyads) and control group (n=25 dyads). Hair cortisol
      concentration was measured in 1-cm-long hair strands, representing 30days of
      exposure before assessment. PTSD and depression symptoms were assessed in the
      mother and child. RESULTS: Women reporting IPV presented with higher hair
      cortisol levels, depression and PTSD symptoms severity in comparison to control
      women. Children who witnessed IPV reported more severe PTSD symptoms, but
      depressive symptoms and hair cortisol were not statistically different than those
      in control children. Correlation analyses revealed a positive association between
      the number of injury events and the level of hair cortisol in children. No
      associations between the hair cortisol levels in mothers and those in their
      children were found. CONCLUSION: Higher hair cortisol levels detected in women
      exposed to IPV reflected long-lasting changes in HPA axis functioning associated
      with chronic stress exposure. Children whose parents recurrently engage in
      violent conflicts with intimate partners may often feel threatened and
      consequently reporting more PTSD-related symptoms. Given that experiencing and
      witnessing violence during childhood and adolescence are predictive of intimate
      partner violence in adulthood, the need of early interventions is crucial.

PMID- 27693889
TI  - The risk of myocardial infarction with aromatase inhibitors relative to tamoxifen
      in post-menopausal women with early stage breast cancer.
AB  - BACKGROUND: Aromatase inhibitors (AIs) may increase cardiovascular risk relative
      to tamoxifen in post-menopausal women with breast cancer. This risk has not been
      well-quantified outside of clinical trials. METHODS: Observational population
      based cohort study of women aged >55 years diagnosed with stage I-III breast
      cancer between 2005 and 2010. Women treated with AIs or tamoxifen were followed
      to March 2012. The primary outcome was hospitalisation for myocardial infarction
      (MI). Cause-specific hazards were compared using tamoxifen as the reference
      group. Inverse probability of treatment weighting using the propensity score was
      used to reduce confounding due to measured baseline covariates. Results were
      confirmed using two cause-specific hazards models. Subgroup analyses included
      women aged >=66 years, those with prior ischaemic heart disease, and a 'lower
      risk group' aged <74 years with stage I-II cancer and no prior ischaemic heart
      disease. RESULTS: In 7409 aromatase inhibitor-treated and 1941 tamoxifen-treated
      women, the median age was 71 versus 74 years, respectively (p < 0.001). Baseline
      prevalence of ischaemic heart disease was similar (17.0% versus 16.9%, p = 0.96).
      Over a mean of 1184 d of follow-up, there were 123 hospitalisations for MI; the
      cause-specific hazard was higher with AIs (hazard ratio 2.02; 95% confidence
      interval 1.16-3.53 in the weighted sample). We observed comparable patterns
      within pre-defined subgroups and when adjusted using cause-specific hazards
      models. CONCLUSION: Aromatase inhibitors are associated with a higher risk of MI
      compared with tamoxifen. This risk should be accounted for when managing
      aromatase inhibitor-treated women.

PMID- 27693890
TI  - Photorespiration and the potential to improve photosynthesis.
AB  - The photorespiratory pathway, in short photorespiration, is an essential
      metabolite repair pathway that allows the photosynthetic CO2 fixation of plants
      to occur in the presence of oxygen. It is necessary because oxygen is a competing
      substrate of the CO2-fixing enzyme ribulose 1,5-bisphosphate carboxylase, forming
      2-phosphoglycolate that negatively interferes with photosynthesis.
      Photorespiration very efficiently recycles 2-phosphoglycolate into 3
      phosphoglycerate, which re-enters the Calvin-Benson cycle to drive sustainable
      photosynthesis. Photorespiration however requires extra energy and re-oxidises
      one quarter of the 2-phosphoglycolate carbon to CO2, lowering potential maximum
      rates of photosynthesis in most plants including food and energy crops. This
      review discusses natural and artificial strategies to reduce the undesired impact
      of air oxygen on photosynthesis and in turn plant growth.

PMID- 27693888
TI  - A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated
      protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid
      tumours.
AB  - PURPOSE: We performed a multi-centre phase I study to assess the safety,
      pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small
      molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, and
      to determine the optimal biological dose for subsequent trials. EXPERIMENTAL
      DESIGN: Patients with treatment-refractory, advanced solid tumours, with adequate
      performance status and organ function were recruited to a dose-escalation study
      in a standard 3 + 3 design. The starting dose was 25 mg orally once weekly with
      toxicity, PK and PD guided dose-escalation with potential to explore alternative
      schedules. RESULTS: Forty-one patients with advanced solid tumours refractory to
      standard therapies and with adequate organ function were recruited in eight
      cohorts up to doses of 150 mg once weekly and 75 mg twice weekly. No dose
      limiting toxicities were observed during the study, and a maximum tolerated dose
      (MTD) was not established. The highest dose cohorts demonstrated sustained
      inhibition of extracellular signal-regulated kinase (ERK) phosphorylation in
      peripheral blood mononuclear cells following ex-vivo phorbol 12-myristate 13
      acetate stimulation. There was a decrease of 70 +/- 26% in mean phosphorylated
      (p)ERK in C1 day 8 tumour biopsies when compared with pre-treatment tumour levels
      in the 75 mg twice a week cohort. Prolonged stable disease (>6 months) was seen
      in two patients, one with cervical cancer and one with ampullary carcinoma.
      CONCLUSIONS: WX-554 was well tolerated, and an optimal biological dose was
      established for further investigation in either a once or twice weekly regimens.
      The recommended phase 2 dose is 75 mg twice weekly.

PMID- 27693892
TI  - Quality rating and private-prices: Evidence from the nursing home industry.
AB  - We use the rollout of the five-star rating of nursing homes to study how private
      pay prices respond to quality rating. We find that star rating increases the
      price differential between top- and bottom-ranked facilities. On average, prices
      of top-ranked facilities increased by 4.8 to 6.0 percent more than the prices of
      bottom-ranked facilities. We find stronger price effects in markets that are less
      concentrated where consumers may have more choices of alternative nursing homes.
      Our results suggest that with simplified design and when markets are less
      concentrated, consumers are more responsive to quality reporting.

PMID- 27693891
TI  - Convergent biosynthetic pathways to beta-lactam antibiotics.
AB  - Five naturally-occurring families of beta-lactams have inspired a class of drugs
      that constitute >60% of the antimicrobials used in human medicine. Their
      biosynthetic pathways reveal highly individualized synthetic strategies that yet
      converge on a common azetidinone ring assembled in structural contexts that
      confer selective binding and inhibition of d,d-transpeptidases that play
      essential roles in bacterial cell wall (peptidoglycan) biosynthesis. These
      enzymes belong to a single 'clan' of evolutionarily distinct serine hydrolases
      whose active site geometry and mechanism of action is specifically matched by
      these antibiotics for inactivation that is kinetically competitive with their
      native function. Unusual enzyme-mediated reactions and catalytic multitasking in
      these pathways are discussed with particular attention to the diverse ways the
      beta-lactam itself is generated, and more broadly how the intrinsic reactivity of
      this core structural element is modulated in natural systems through the
      introduction of ring strain and electronic effects.

PMID- 27693893
TI  - How product standardization affects choice: Evidence from the Massachusetts
      Health Insurance Exchange.
AB  - This paper examines the effect of choice architecture on Massachusetts' Health
      Insurance Exchange. A policy change standardized cost-sharing parameters of plans
      across insurers and altered information presentation. Post-change, consumers
      chose more generous plans and different brands, but were not more price
      sensitive. We use a discrete choice model that allows the policy to affect how
      attributes are valued to decompose the policy's effects into a valuation effect
      and a product availability effect. The brand shifts are largely explained by the
      availability effect and the generosity shift by the valuation effect. A
      hypothetical choice experiment replicates our results and explores alternative
      counterfactuals.

PMID- 27693894
TI  - Antibacterial mechanism of daptomycin antibiotic against Staphylococcus aureus
      based on a quantitative bacterial proteome analysis.
AB  - : Daptomycin (DAP) is a novel lipopeptide antibiotic which exhibits excellent
      antibacterial activity against most clinically relevant Gram-positive bacteria,
      but the DAP-targeting protein molecules against host bacterial infection are far
      from clear. In order to discover bacterial protein response to DAP treatment, an
      iTRAQ-based quantitative proteomic analysis was applied to identify differential
      bacterial proteome profiling of Staphylococcus aureus (S. aureus) ATCC 25923 to
      0.125MUg/ml DAP exposure. Totally 51 bacterial proteins were significantly
      changed with DAP treatment, among which 34 proteins were obviously up-regulated
      and 17 proteins were down-regulated. Meanwhile, 139 bacterial cell membrane (CM)
      proteins were identified, and 7 CM proteins were significantly altered to
      decrease CM potential to disrupt bacterial cell membrane. Especially the up
      regulation of NDK and down-regulation of NT5 in several S. aureus strains are
      validated to be a universal variation tendency response to DAP treatment. Under
      DAP exposure, bacterial membrane potential is decreased and cell membrane is
      disrupted, and bacterial chromosome is aggregated, which contributes to bacterial
      DNA rapid release and induces bacteria death within 2-5h. In general, multiple
      bacterial protein expressions are changed in response to DAP antibiotic exposure,
      which disrupts host bacterial physiology by multiple cellular levels. To our
      knowledge, this is the first time to exactly identify infectious bacterial
      proteins in response to DAP antibiotic action. Our findings help better
      understand DAP antibacterial mechanism and develop novel DAP derivatives against
      the upcoming antibiotic-resistant bacterial infection. BIOLOGICAL SIGNIFICANCE:
      DAP is a novel lipopeptide antibiotic that it exhibits excellent in vitro
      activity against most clinically relevant Gram-positive bacteria, and the
      investigations on its pharmaceutical action mode of DAP have dramatically
      increased in the past decade due to its unique antimicrobial mechanism. However,
      the target molecules of DAP acting on the infectious bacteria, are far from
      clear. The state-of-the-art quantitative proteomic technologies provide new
      avenues to uncover underlying mechanism of antibiotics. Our research main aims to
      identify bacterial proteome profiling of host strain S. aureus response to DAP
      treatment through an iTRAQ-based quantitative proteomic analysis, which
      contributes to understand DAP efficient antibacterial activity and the microbial
      antibiotic interactions.

PMID- 27693895
TI  - Missed Opportunities: A Mixed-Methods Analysis of CAM Discussions and Practices
      in the Management of Pain in Oncology.
AB  - CONTEXT: Treatment of pain in cancer is a clinical priority. Many cancer patients
      seek and use complementary and alternative medicine (CAM) therapies. OBJECTIVES:
      The aim of this study was to describe the role CAM plays in oncology, clinicians'
      approaches to pain management and its alignment with patient preference and self
      care. METHODS: We used quantitative criteria to identify patients with high, self
      reported pain and reduced quality of life. For these patients, we merged
      quantitative and qualitative data from encounter audio recordings, patient
      surveys, and the medical record. RESULTS: We identified 32 patients (72% women,
      average age 60) experiencing significantly symptomatic pain at enrollment. Merged
      themes were 1) Restricted and defined roles: Oncology clinicians suggested and
      documented cancer-specific approaches to pain management. Patients often (17,
      53%) used CAM but rarely desired to discuss it in their encounters. 2) Proactive
      patients in setting of neutrality: Pain management strategies were considered in
      22 instances. CAM was mentioned in 4 (18%) of these discussions but only after
      patient initiation. Clinicians took a neutral stance. 3) Missed opportunities for
      person-centered CAM discussions and management: Most (88%) patients were
      receiving conventional pain medications at enrollment or had them added or
      escalated during follow-up. Some patients in pain expressed preferences for
      avoiding opioids. One patient reported wishing CAM would have been discussed
      after an encounter in which it was not. CONCLUSION: Bringing CAM discussions into
      the oncology encounter may facilitate a stronger patient-clinician partnership
      and a more open and safe understanding of pain-related CAM use.

PMID- 27693896
TI  - The Association Between Pain and Clinical Outcomes in Adolescents With Cystic
      Fibrosis.
AB  - CONTEXT: Pain is a common problem in patients with cystic fibrosis (CF) and in
      adults is associated with lower quality of life and more pulmonary complications.
      Less is known about the impact of pain in adolescents with CF. OBJECTIVES: This
      study aimed to describe pain in an adolescent CF population and to determine if
      pain at baseline is associated with lower health-related quality of life (HRQoL)
      and worse pulmonary outcomes at six-month follow-up. METHODS: We administered
      surveys at baseline and at six months to CF patients aged 12 to 20 years.
      Analyses included Wilcoxon log-rank tests, Spearman correlations, and linear and
      logistic regressions. RESULTS: Seventy-three patients (86.9%) completed the
      baseline questionnaire and 53 patients (63.1%) completed the six-month follow-up
      questionnaire. Mean age was 15.6 +/- 2.5 and mean FEV1 was 79 +/- 26% predicted;
      89% of patients reported pain in the three months before the survey, but in most
      it was short lived and mild to moderate in severity. Abdominal pain was the most
      common location. Pain was associated with increased pulmonary exacerbations (odds
      ratios = 1.99 for every one-point increase on a composite pain scale, P = 0.03)
      and with lower HRQoL. CONCLUSIONS: Pain in adolescents with CF is associated with
      lower HRQoL and more pulmonary exacerbations. Greater efforts are needed to
      manage pain in this population and to determine if treatment of pain improves
      other outcomes.

PMID- 27693897
TI  - Authors' Reply to Davies et al.

PMID- 27693898
TI  - EffenDys-Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in
      Patients With Advanced Cancer: A Multicenter, Open-Label, Randomized, Morphine
      Controlled, Crossover, Phase II Trial.
AB  - CONTEXT: Episodic breathlessness is a frequent and burdensome symptom in cancer
      patients but pharmacological treatment is limited. OBJECTIVES: To determine time
      to onset, efficacy, feasibility, and safety of transmucosal fentanyl in
      comparison to immediate-release morphine for the relief of episodic
      breathlessness. METHODS: Phase II, investigator-initiated, multicenter, open
      label, randomized, morphine-controlled, crossover trial with open-label titration
      of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary
      outcome was time to onset of meaningful breathlessness relief. Secondary outcomes
      were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of
      breathlessness intensity difference at 15 and 60 minutes), feasibility, and
      safety. Study was approved by local ethics committees. RESULTS: Twenty-five of
      1341 patients were eligible, 10 patients agreed to participate (four female, mean
      age 58 +/- 11, mean Karnofsky score 67 +/- 11). Two patients died before final
      visits and two patients dropped-out because of disease progression leaving six
      patients for analysis with 61 episodes of breathlessness. Mean time to onset was
      for FBT 12.7 +/- 10.0 and for immediate-release morphine 23.6 +/- 15.1 minutes
      with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094).
      Efficacy measures were predominately in favor for FBT. Both interventions were
      safe. Feasibility failed because of too much study demands for a very ill patient
      group. CONCLUSION: The description of a faster and greater relief of episodic
      breathlessness by transmucosal fentanyl versus morphine justifies further
      evaluation by a full-powered trial.

PMID- 27693899
TI  - A Comparison of Circumstances at the End of Life in a Hospital Setting for
      Children With Palliative Care Involvement Versus Those Without.
AB  - CONTEXT: Specialized pediatric palliative care (PPC) services have become more
      common in urban pediatric hospital settings, although little is known about
      palliative care specialist involvement. OBJECTIVES: The objective of this study
      was to compare circumstances before death in children who spent their last days
      of life in an inpatient pediatric hospital setting, with or without PPC provider
      involvement during their inpatient stay. METHODS: Retrospective chart review of
      medical records of children for the last inpatient stay that resulted in death at
      a children's hospital setting between January 2012 through June 2013. The setting
      was a free-standing, 385-bed tertiary care children's hospital. RESULTS: Charts
      were reviewed for 114 children between 0 and 18 years of age, who were
      hospitalized for at least 24 hours before their death. Half of the children who
      died as inpatients were infants (median age five weeks). Children who received an
      inpatient PPC consult (25% of the sample) experienced 1) a higher rate of pain
      assessments, 2) better documentation around specific actions to manage pain, 3)
      greater odds of receiving integrative medicine services, 4) fewer
      diagnostic/monitoring procedures (e.g., blood gases, blood draws, placements of
      intravenous lines) in the last 48 hours of life, and 5) nearly eight times
      greater odds of having a do-not-resuscitate order in place at the time of death.
      CONCLUSION: The integration of a PPC team was associated with fewer
      diagnostic/monitoring procedures and improved pain management documentation in
      this study of 114 children who died as inpatients.

PMID- 27693900
TI  - Pain Assessment, Management, and Control Among Patients 65 Years or Older
      Receiving Hospice Care in the U.S.
AB  - CONTEXT: Knowledge is limited regarding pain assessment and management practices,
      as well as pain-related outcomes in hospice care. OBJECTIVES: To generate
      national estimates of pain assessment and management practices and outcomes of
      pain control among patients 65 years or older receiving hospice care in the U.S.
      and identify hospice discharge and agency characteristics predicting study
      outcomes. METHODS: The 2007 National Home Health and Hospice Care Survey was
      analyzed. Multivariate logistic regressions were estimated to identify discharge
      and agency characteristics predicting guideline-concordant pain assessment and
      management practices and pain control outcomes. RESULTS: A high percentage of
      discharges had pain assessment at admission (97%) and before discharge (93%); use
      of valid pain rating scales was relatively low (69% and 54% for first and last
      assessments, respectively). Almost 95% of patients received pain medication, but
      only 42% received nonpharmacologic therapies. About 70% of patients assessed with
      a valid pain scale saw improvement in the level of pain or remained free of pain
      from admission to discharge. Non-Hispanic blacks were less likely to have pain
      assessments, and Hispanics were less likely to receive opioid analgesics or to
      have pain-free status at discharge, compared with non-Hispanic whites. Patients
      receiving care from for-profit (vs. nonprofit) agencies were more likely to
      receive pain assessment with a valid scale before discharge but less likely to
      experience pain control or improvement. CONCLUSION: Greater use of valid pain
      assessment scales and nonpharmacologic therapies constitutes areas for
      improvement in hospice care. Targeted interventions are needed to address
      disparities in pain care by patient race and/or ethnicity and agency ownership
      status.

PMID- 27693901
TI  - Efficacy and Safety of Two Methadone Titration Methods for the Treatment of
      Cancer-Related Pain: The EQUIMETH2 Trial (Methadone for Cancer-Related Pain).
AB  - CONTEXT: In the European Association for Palliative Care recommendations for
      cancer pain management, there was no consensus regarding the indications,
      titration, or monitoring of methadone. OBJECTIVES: This national, randomized,
      multicenter trial aimed to compare two methadone titration methods (stop-and-go
      vs. progressive) in patients with cancer-related pain who were inadequately
      relieved by or intolerant to Level 3 opioids. METHODS: The primary end point was
      the rate of success/failure at Day 4, defined as pain relief (reduction of at
      least two points on the visual scale and a pain score <5 for two consecutive
      days) and no overdose (Rudkin scale >=3 and respiratory rate <8/minute). The
      patients were followed for two months after enrollment. RESULTS: The cancer
      related pain characteristics of the 146 patients were as follows: 16% were
      nociceptive, 85% experienced breakthrough pain, and 84% had mixed types of pain.
      The reasons for switching to methadone were a lack of efficacy that was either
      isolated (56%) or associated with intolerance (38%). Adequate pain relief was
      obtained in 80% of the patients (median of three days in both groups [P = 0.12])
      and lasted until D56. The rate of success/failure was approximately 40% at Day 4
      in both groups, with overdoses in 13% of the patients throughout the study. The
      two methods were considered equally easy to perform by nearly 60% of the
      clinicians. CONCLUSION: Methadone is an effective and sustainable second-line
      alternative opioid for the treatment of cancer-related pain. The methods of
      titration are comparable in terms of efficacy, safety, and ease of use.

PMID- 27693902
TI  - The Effect of Pediatric Palliative Care Policy on Hospice Utilization Among
      California Medicaid Beneficiaries.
AB  - CONTEXT: California implemented pediatric palliative care legislations that
      allowed children to receive curative and supportive care from diagnosis of a life
      threatening serious illness in 2010. Palliative care policies may improve access
      to hospice care as children near end of life. OBJECTIVES: The aim of this study
      was to examine the effect of the palliative care policy on hospice utilization
      for children and their families was investigated. METHODS: Using 2007 and 2010
      California Medicaid data, a difference-in-difference analysis was conducted to
      analyze hospice use (i.e., hospice enrollment, hospice length of stay) changes
      for children who resided in pediatric policy counties relative to those who did
      not. The sample of children in California who died with a life-threatening
      serious illness in 2007 and 2010 equaled 979 children. RESULTS: More than 10% of
      children enrolled in hospice care with an average of less than 3 days of hospice
      care. The palliative care policy did not have any effect on hospice enrollment.
      However, the policy was positively associated with increasing days in hospice
      care (incidence rate ratio = 5.61, P < 0.05). The rate of hospice length of stay
      increased by a factor of 5.61 for children in palliative care counties compared
      with children unaffected by the policy. CONCLUSION: The pediatric palliative care
      policy was associated with longer lengths of stay in hospice once the children
      were enrolled. Policies promoting palliative care are critical to ensuring access
      to hospice care for children.

PMID- 27693903
TI  - Reliability and Validity of the Spanish Version of the Memorial Symptom
      Assessment Scale in Oncology Patients.
AB  - CONTEXT: Memorial Symptom Assessment Scale (MSAS) is a multidimensional tool
      developed to evaluate frequency, severity, and distress of common symptoms
      present in cancer patients. OBJECTIVE: To translate the original English version
      of MSAS and prove the reliability and validity of the Spanish version. METHODS:
      MSAS scale was translated into Spanish and administered to 246 cancer patients
      aged between 18 and 85 years. They attended the Day Hospital to receive
      chemotherapy. European Organization for Research and Treatment of Cancer Quality
      of Life Questionnaire-Core 30 and Rotterdam Symptom Checklist were used to test
      criterion validity. RESULTS: TOTAL MSAS, Physical Symptom Subscale (PHYS),
      Psychological Symptom Subscale (PSYCH), and Global Distress Index (GDI) reported
      high internal consistency: 0.891, 0.801, 0.825, 0.813, respectively. Exploratory
      factor analysis identified two-factors structure and confirmatory factor analysis
      showed good adjustment rates. The emotional functioning subscale of European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      Core 30 highly correlated with PSYCH (r = -0.868; P < 0.001) and GDI (r = -0.810;
      P < 0.001), whereas social functioning subscale correlated with PSYCH (r = 
      0.704; P < 0.001) and GDI (r = -0.624; P < 0.001). The PHYS of Rotterdam Symptom
      Checklist correlated with PHYS (r = 0.876; P < 0.001) and the PSYCH with PSYCH (r
      = 0.872; P < 0.001). CONCLUSION: The Spanish version of MSAS was determined to be
      a valid and reliable scale in cancer patients.

PMID- 27693904
TI  - Developing a Medical School Curriculum for Psychological, Moral, and Spiritual
      Wellness: Student and Faculty Perspectives.
AB  - CONTEXT: Although many studies have addressed the integration of a religion
      and/or spirituality curriculum into medical school training, few describe the
      process of curriculum development based on qualitative data from students and
      faculty. OBJECTIVES: The aim of this study is to explore the perspectives of
      medical students and chaplaincy trainees regarding the development of a
      curriculum to facilitate reflection on moral and spiritual dimensions of caring
      for the critically ill and to train students in self-care practices that promote
      professionalism. METHODS: Research staff conducted semiscripted and one-on-one
      interviews and focus groups. Respondents also completed a short and self-reported
      demographic questionnaire. Participants included 44 students and faculty members
      from Harvard Medical School and Harvard Divinity School, specifically senior
      medical students and divinity school students who have undergone chaplaincy
      training. RESULTS: Two major qualitative themes emerged: curriculum format and
      curriculum content. Inter-rater reliability was high (kappa = 0.75). With regard
      to curriculum format, most participants supported the curriculum being
      longitudinal, elective, and experiential. With regard to curriculum content, five
      subthemes emerged: personal religious and/or spiritual (R/S) growth, professional
      integration of R/S values, addressing patient needs, structural and/or
      institutional dynamics within the health care system, and controversial social
      issues. CONCLUSION: Qualitative findings of this study suggest that development
      of a future medical school curriculum on R/S and wellness should be elective,
      longitudinal, and experiential and should focus on the impact and integration of
      R/S values and self-care practices within self, care for patients, and the
      medical team. Future research is necessary to study the efficacy of these
      curricula once implemented.

PMID- 27693906
TI  - Beyond blindness: On the role of organism and environment in trial generation.
AB  - In this paper we aim to amend the traditional analogy at the heart of
      evolutionary epistemologies. We shall first argue, contrary to what has been
      frequently done, that both hypothesis generation and the processes of generation
      of genetic and phenotypic change are often directed as well as environmentally
      conditioned. Secondly, we shall argue that environmental influence does not
      affect trial generation directly but that environmental information is processed
      by the epistemic agent and by the biological organism respectively. Thirdly, we
      suggest conceiving hypothesis generation as a process of manipulative abduction
      and the generation of biological variation as a process mediated by phenotypic
      plasticity. Finally, we argue that manipulative abduction and environmentally
      induced biological variation modulated by plasticity are analogous because they
      both involve a conjectural response to environmental cues. Our analysis thus
      vindicates a revised version of evolutionary epistemology ascribing a fundamental
      role to both organism and environment in trial generation. This perspective, in
      our opinion, offers support to the thesis, inspired by the theory of embodied
      cognition, that hypothesis generation is sometimes explained by an appeal to
      phenotypic plasticity.

PMID- 27693905
TI  - Cognitive and emotional processing of pleasant and unpleasant experiences in
      major depression: A matter of vantage point?
AB  - BACKGROUND AND OBJECTIVES: In nonclinical populations, adopting a third-person
      perspective as opposed to a first-person perspective while analyzing negative
      emotional experiences fosters understanding of these experiences and reduces
      negative emotional reactivity. We assessed whether this generalizes to people
      with major depression (MD). Additionally, we assessed whether the emotion
      reducing effects of adopting a third-person perspective also occur when subjects
      with MD and HC subjects analyze positive experiences. METHODS: Seventy-two MD
      subjects and 82 HC subjects analyzed a happy and a negative experience from
      either a first-person or a third-person perspective. RESULTS: Unexpectedly, we
      found no emotion-reducing effects of third-person perspective in either group
      thinking about negative events. However, across groups, third-person perspective
      was associated with less recounting of negative experiences and with a clearer,
      more coherent understanding of them. Negative affect decreased and positive
      affect increased in both groups analyzing happy experiences. In MD subjects,
      decreases in depressive affect were stronger for the third-person perspective. In
      both groups, positive affect increased and negative affect decreased more
      strongly for the third-person perspective. LIMITATIONS: While reflecting on their
      positive memory, MD subjects adopted their assigned perspective for a shorter
      amount of time (70%) than HC subjects (78%). However, percentage of time
      participants adopted their assigned perspective was unrelated to the significant
      effects we found. CONCLUSIONS: Both people suffering from MD and healthy
      individuals may benefit from processing pleasant experiences, especially when
      adopting a self-distant perspective.

PMID- 27693907
TI  - An infrared diagnostic system to detect causal agents of grapevine trunk
      diseases.
AB  - In most vineyards worldwide, agents of grapevine trunk diseases represent a real
      threat for viticulture and are responsible for significant economic loss to the
      wine industry. The conventional microbiological isolation technique used to
      diagnose this disease is tedious and frequently leads to false negatives. Thus, a
      dire need exists for an alternative method to detect this disease. One possible
      way involves infrared spectroscopy, which is a rapid, nondestructive analytical
      tool that is commonly used for quality control of feed stuffs. In the present
      work, a midinfrared spectrometer was tested as a fast tool for detecting agents
      of grapevine trunk disease. Midinfrared spectra were collected from 70 Vitis
      vinifera L. cv. Cabernet-Sauvignon one year old trunk-wood samples that were
      infected naturally in one viticulture nursery of the south of France. The samples
      underwent polymerase chain reaction and morphological identification, and the
      results were correlated to the midinfrared spectra by using multivariate analysis
      to discriminate between noninfected and infected samples. Based on comparison
      with some control samples, the highest percentage of correct identification of
      fungal contamination when using the midinfrared spectroscopy method is 80%.

PMID- 27693908
TI  - Multicenter evaluation of molecular and culture-dependent diagnostics for
      Shigella species and Entero-invasive Escherichia coli in the Netherlands.
AB  - An inter-laboratory collaborative trial for the evaluation of diagnostics for
      detection and identification of Shigella species and Entero-invasive Escherichia
      coli (EIEC) was performed. Sixteen Medical Microbiological Laboratories (MMLs)
      participated. MMLs were interviewed about their diagnostic methods and a sample
      panel, consisting of DNA-extracts and spiked stool samples with different
      concentrations of Shigella flexneri, was provided to each MML. The results of the
      trial showed an enormous variety in culture-dependent and molecular diagnostic
      techniques currently used among MMLs. Despite the various molecular procedures,
      15 out of 16 MMLs were able to detect Shigella species or EIEC in all the samples
      provided, showing that the diversity of methods has no effect on the qualitative
      detection of Shigella flexneri. In contrast to semi quantitative analysis, the
      minimum and maximum values per sample differed by approximately five threshold
      cycles (Ct-value) between the MMLs included in the study. This indicates that
      defining a uniform Ct-value cut-off for notification to health authorities is not
      advisable.

PMID- 27693909
TI  - Regulation of actin filament turnover by cofilin-1 and cytoplasmic tropomyosin
      isoforms.
AB  - Tropomyosin and cofilin are actin-binding proteins which control dynamics of
      actin assembly and disassembly. Tropomyosin isoforms can either inhibit or
      enhance cofilin activity, but the mechanism of this diverse regulation is not
      well understood. In this work mechanisms of actin dynamics regulation by four
      cytoskeletal tropomyosin isoforms and cofilin-1 were studied with the use of
      biochemical and fluorescent microscopy assays. The recombinant tropomyosin
      isoforms were products of two genes: TPM1 (Tpm1.6 and Tpm1.8) and TPM3 (Tpm3.2
      and Tpm3.4). Tpm1.6/1.8 bound to F-actin with higher apparent binding constants
      and lower cooperativities than Tpm3.2/3.4. In consequence, subsaturating
      concentrations of cofilin-1 removed 50% of Tpm3.2/3.4 from F-actin. By contrast,
      2 and 5.5 molar excess of cofilin-1 over actin was required to dissociate 50% of
      Tpm1.6/1.8. All tropomyosins inhibited the rate of spontaneous polymerization of
      actin, which was reversed by cofilin-1. Products of TPM1 favored longer filaments
      and protected them from cofilin-induced depolymerization. This was in contrast to
      the isoforms derived from TPM3, which facilitated depolymerization. Tpm3.4 was
      the only isoform, which increased frequency of the filament severing by cofilin
      1. Tpm1.6/1.8 inhibited, but Tpm3.2/3.4 enhanced cofilin-induced conformational
      changes leading to accelerated release of rhodamine-phalloidin from the filament.
      We concluded that the effects were executed through different actin affinities of
      tropomyosin isoforms and cooperativities of tropomyosin and cofilin-1 binding.
      The results obtained in vitro were in good agreement with localization of
      tropomyosin isoforms in stable or highly dynamic filaments demonstrated before in
      various cells.

PMID- 27693910
TI  - Is the clinical relevance of drug-food and drug-herb interactions limited to
      grapefruit juice and Saint-John's Wort?
AB  - An interaction of drug with food, herbs, and dietary supplements is usually the
      consequence of a physical, chemical or physiologic relationship between a drug
      and a product consumed as food, nutritional supplement or over-the-counter
      medicinal plant. The current educational review aims at reminding to the
      prescribing physicians that the most clinically relevant drug-food interactions
      may not be strictly limited to those with grapefruit juice and with the Saint
      John's Wort herbal extract and may be responsible for changes in drug plasma
      concentrations, which in turn decrease efficacy or led to sometimes life
      threatening toxicity. Common situations handled in clinical practice such as
      aging, concomitant medications, transplant recipients, patients with cancer,
      malnutrition, HIV infection and those receiving enteral or parenteral feeding may
      be at increased risk of drug-food or drug-herb interactions. Medications with
      narrow therapeutic index or potential life-threatening toxicity, e.g., the non
      steroidal anti-inflammatory drugs, opioid analgesics, cardiovascular medications,
      warfarin, anticancer drugs and immunosuppressants may be at risk of significant
      drug-food interactions to occur. Despite the fact that considerable effort has
      been achieved to increase patient' and doctor's information and ability to
      anticipate their occurrence and consequences in clinical practice, a thorough and
      detailed health history and dietary recall are essential for identifying
      potential problems in order to optimize patient prescriptions and drug dosing on
      an individual basis as well as to increase the treatment risk/benefit ratio.

PMID- 27693911
TI  - Total synthesis and the anticancer activity of (+)-spisulosine.
AB  - The total synthesis of the anticancer agent (+)-spisulosine has been
      accomplished. The strategy involved a substrate-controlled aza-Claisen
      rearrangement to establish the erythro-configured amino-alcohol motif followed by
      deoxygenation to create a methyl side-chain. Subsequent Wittig olefination then
      permitted the construction of the carbon backbone of the target molecule. To
      investigate the antiproliferative effect of 1, its biological profile was
      examined on a panel of 6 human malignant cell lines and demonstrated the
      significant anticancer activity of 1 on at least five of the evaluated lines with
      IC50 < 1 MUM (MCF-7, HTC-116, Caco-2, Jurkat and HeLa).

PMID- 27693912
TI  - Diastereoselective synthesis of furanose and pyranose substituted glycine and
      alanine derivatives via proline-catalyzed asymmetric alpha-amination of
      aldehydes.
AB  - A concise organocatalytic route toward the synthesis of furanose and pyranose
      substituted glycine and alanine derivatives is reported. These compounds are core
      structural units of some of the naturally available antibiotics and antifungal
      agents. Proline-catalyzed asymmetric alpha-amination of aldehydes derived from
      sugars is used as the key reaction to synthesize twelve sugar amino acid
      derivatives. The asymmetric transformations proceeded in good yields and with
      good to excellent diastereoselectivity. The application of the synthesized amino
      acids is demonstrated by synthesizing a tripeptide containing one of them.

PMID- 27693913
TI  - Differential subcellular distribution of four phospholipase C isoforms and
      secretion of GPI-PLC activity.
AB  - Phospholipase C (PLC) is an important enzyme of signal transduction pathways by
      generation of second messengers from membrane lipids. PLCs are also indicated to
      cleave glycosylphosphatidylinositol (GPI)-anchors of surface proteins thus
      releasing these into the environment. However, it remains unknown whether this
      enzymatic activity on the surface is due to distinct PLC isoforms in higher
      eukaryotes. Ciliates have, in contrast to other unicellular eukaryotes, multiple
      PLC isoforms as mammals do. Thus, Paramecium represents a perfect model to study
      subcellular distribution and potential surface activity of PLC isoforms. We have
      identified distinct subcellular localizations of four PLC isoforms indicating
      functional specialization. The association with different calcium release
      channels (CRCs) argues for distinct subcellular functions. They may serve as PI
      PLCs in microdomains for local second messenger responses rather than free
      floating IP3. In addition, all isoforms can be found on the cell surface and they
      are found together with GPI-cleaved surface proteins in salt/ethanol washes of
      cells. We can moreover show them in medium supernatants of living cells where
      they have access to GPI-anchored surface proteins. Among the isoforms we cannot
      assign GPI-PLC activity to specific PLC isoforms; rather each PLC is potentially
      responsible for the release of GPI-anchored proteins from the surface.

PMID- 27693914
TI  - Specific interaction of IM30/Vipp1 with cyanobacterial and chloroplast membranes
      results in membrane remodeling and eventually in membrane fusion.
AB  - The photosynthetic light reaction takes place within the thylakoid membrane
      system in cyanobacteria and chloroplasts. Besides its global importance, the
      biogenesis, maintenance and dynamics of this membrane system are still a mystery.
      In the last two decades, strong evidence supported the idea that these processes
      involve IM30, the inner membrane-associated protein of 30kDa, a protein also
      known as the vesicle-inducing protein in plastids 1 (Vipp1). Even though we just
      only begin to understand the precise physiological function of this protein, it
      is clear that interaction of IM30 with membranes is crucial for biogenesis of
      thylakoid membranes. Here we summarize and discuss forces guiding IM30-membrane
      interactions, as the membrane properties as well as the oligomeric state of IM30
      appear to affect proper interaction of IM30 with membrane surfaces. Interaction
      of IM30 with membranes results in an altered membrane structure and can finally
      trigger fusion of adjacent membranes, when Mg2+ is present. Based on recent
      results, we finally present a model summarizing individual steps involved in IM30
      mediated membrane fusion. This article is part of a Special Issue entitled: Lipid
      order/lipid defects and lipid-control of protein activity edited by Dirk
      Schneider.

PMID- 27693916
TI  - Inducible costimulator (ICOS) potentiates TCR-induced calcium flux by augmenting
      PLCgamma1 activation and actin remodeling.
AB  - The inducible costimulator (ICOS) is a T cell costimulatory receptor that plays
      crucial roles in T cell differentiation and function. So far, ICOS has been shown
      to activate three signaling components: phosphoinositide 3-kinase (PI3K),
      intracellular calcium mobilization, and TANK binding kinase 1 (TBK1). By
      generating a knock-in strain of mice in which the ICOS gene is modified such that
      the ICOS-mediated PI3K pathway is selectively abrogated while the capacity of
      ICOS to mobilize intracellular calcium remains intact, we have shown that ICOS
      mediated PI3K activation is required for some but not all T cell responses. This
      suggests that the ICOS-calcium signaling axis may explain some of the PI3K
      independent ICOS functions. Further, a recent in vivo imaging study indicated
      that ICOS-dependent intracellular calcium flux facilitates cognate T cell-B cell
      interactions within the germinal center. However, how ICOS promotes TCR-mediated
      calcium flux has not been clear. Here we identified a membrane proximal motif in
      the cytoplasmic tail of ICOS that is essential for ICOS-assisted calcium
      signaling and demonstrate that ICOS can induce calcium flux independently of
      other signaling motifs. We also provide evidence that ICOS potentiates
      phospholipase Cgamma1 (PLCgamma1) activation to enhance calcium release from the
      intracellular pool. In parallel, acute ligation of ICOS without TCR co-engagement
      leads to activation of small GTPases, RhoA and Cdc42, consistent with the
      capacity of ICOS to induce actin remodeling. Importantly, interruption of actin
      dynamics during acute TCR or TCR-ICOS co-ligation severely impairs calcium flux
      in T cells even in the presence of activated PLCgamma1. Thus, ICOS potentiates
      TCR-induced calcium flux by enhancing PLCgamma1 activation and actin remodeling
      in a coordinated manner.

PMID- 27693915
TI  - TLR9 played a more important role than TLR2 in the combination of maltose-binding
      protein and BCG-induced Th1 activation.
AB  - Our previous study demonstrated that maltose-binding protein (MBP) combined with
      BCG induced synergistic mouse Th1 activation in vivo. Here, to explore the
      mechanism of MBP combined with BCG on Th1 activation, mouse purified CD4+ T cells
      were stimulated with MBP and BCG in vitro. The results showed that MBP combined
      with BCG synergistically increased IFN-gamma production, accompanied with the
      upregulation of TLR2/9 expressions, suggesting that TLR2/9 were involved in the
      combination-induced Th1 activation. Next, TLR2 antibodies and TLR9 inhibitor were
      used to further analyze the effects of TLRs in Th1 activation. Results showed
      TLR2 antibody partly decreased MBP combined with BCG-induced IFN-gamma
      production, MyD88 expression and IkappaB phosphorylation, indicating that TLR2
      mediated MyD88-dependent pathway was involved in the MBP combined with BCG
      induced Th1 activation. Moreover, MBP combined with BCG-induced Th1 activation
      was completely abrogated by TLR9 inhibitor, suggesting that TLR9-mediated MyD88
      dependent pathway played a more important role than TLR2 in the combination
      induced Th1 activation. Further study showed that TLR9 inhibitor downregulated
      TLR2 expression, suggesting that TLR9 signaling regulated TLR2 activation to
      favor Th1 resonse induced by MBP combined with BCG. Collectively, we demonstrated
      for the first time that the cross-talk of TLR2 and TLR9 triggered Th1 activation
      collaboratively and our findings provided valuable information about designing
      more effective adjuvant for cancer therapy.

PMID- 27693917
TI  - T-cell clones from Th1, Th17 or Th1/17 lineages and their signature cytokines
      have different capacity to activate endothelial cells or synoviocytes.
AB  - OBJECTIVE: To compare the direct effect of cytokines on synoviocytes and
      endothelial cells to the effects of supernatants from Th1, Th17 and Th1/17 clones
      and the direct cell-cell interactions with the same clones. METHODS: Th17 and
      Th1/17 clones were obtained from the CD161+CCR6+ fraction and Th1 clones from the
      CD161-CCR6- fraction of human CD4+ T-cells. Endothelial cells or synoviocytes
      were cultured in the presence of either isolated pro-inflammatory cytokines (IL
      17 and/or TNF-alpha) or supernatants from the T-cell clones or co-cultured with T
      cell clones themselves. IL-6 and IL-8 expression and production were analyzed.
      RESULTS: IL-17 and TNF-alpha induced IL-6 and IL-8 expression, although IL-17
      alone had a limited effect on endothelial cells compared to synoviocytes.
      Supernatants from activated T-helper clones also induced IL-6 and IL-8 expression
      but with discrepancies between endothelial cells and synoviocytes. Endothelial
      cells were mostly activated by Th1 clone supernatants whereas synoviocytes were
      activated by all T-cell subtypes. Finally, cell-cell contact experiments showed a
      great heterogeneity among cell clones, even from the same lineage. IL-6
      expression was mostly induced by contact with Th1 clones both in endothelial and
      mesenchymal cells whereas IL-8 expression was induced by all T-cell clones
      whatever their phenotype. CONCLUSION: We showed that endothelial cells were much
      more sensitive to Th1 activation whereas synoviocytes were activated by all T
      helper lineages. This work highlights the heterogeneity of interactions between T
      cells and stromal cells through soluble factors or direct cell contact.

PMID- 27693918
TI  - Identification of heat shock protein A9 as a Tembusu virus binding protein on DF
      1 cells.
AB  - This study attempts to identify receptor elements for Tembusu virus (TMUV) on DF
      1 cells. Using co-immunoprecipitation and virus overlay protein binding assays,
      we identified a TMUV-binding protein of approximately 70-kDa on DF-1 cell
      membranes. Mass spectroscopy identified the protein to be heat shock protein
      (HSP) A9, which was reconfirmed by an anti-HSPA9 antibody. Indirect
      immunofluorescence demonstrated a significant degree of colocalization between
      HSPA9 and TMUV on cell surface. Additionally, an antibody against HSPA9 could
      inhibit TMUV infection in DF-1 cells in a dose-dependent manner. These results
      might suggest that HSPA9 is a putative receptor for TMUV.

PMID- 27693920
TI  - The stress granule component G3BP is a novel interaction partner for the nuclear
      shuttle proteins of the nanovirus pea necrotic yellow dwarf virus and geminivirus
      abutilon mosaic virus.
AB  - Stress granules (SGs) are structures within cells that regulate gene expression
      during stress response, e.g. viral infection. In mammalian cells assembly of SGs
      is dependent on the Ras-GAP SH3-domain-binding protein (G3BP). The C-terminal
      domain of the viral nonstructural protein 3 (nsP3) of Semliki Forest virus (SFV)
      forms a complex with mammalian G3BP and sequesters it into viral RNA replication
      complexes in a manner that inhibits the formation of SGs. The binding domain of
      nsP3 to HsG3BP was mapped to two tandem 'FGDF' repeat motifs close to the C
      terminus of the viral proteins. It was speculated that plant viruses employ a
      similar strategy to inhibit SG function. This study identifies an Arabidopsis
      thaliana NTF2-RRM domain-containing protein as a G3BP-like protein (AtG3BP),
      which localizes to plant SGs. Moreover, the nuclear shuttle protein (NSP) of the
      begomovirus abutilon mosaic virus (AbMV), which harbors a 'FVSF'-motif at its C
      terminal end, interacts with the AtG3BP-like protein, as does the 'FNGSF'-motif
      containing NSP of pea necrotic yellow dwarf virus (PNYDV), a member of the
      Nanoviridae family. We therefore propose that SG formation upon stress is
      conserved between mammalian and plant cells and that plant viruses may follow a
      similar strategy to inhibit plant SG function as it has been shown for their
      mammalian counterparts.

PMID- 27693919
TI  - Differential response of cassava genotypes to infection by cassava mosaic
      geminiviruses.
AB  - Mitigation of cassava mosaic disease (CMD) focuses on the introgression of
      resistance imparted by the polygenic recessive (CMD1), dominant monogenic (CMD2)
      and CMD3 loci. The mechanism(s) of resistance they impart, however, remain
      unknown. Two CMD susceptible and nine CMD resistant cassava genotypes were
      inoculated by microparticle bombardment with infectious clones of African cassava
      mosaic virus Cameroon strain (ACMV-CM) and the Kenyan strain K201 of East African
      cassava mosaic virus (EACMV KE2 [K201]). Genotypes carrying the CMD1 (TMS 30572),
      CMD2 (TME 3, TME 204 and Oko-iyawo) and CMD3 (TMS 97/0505) resistance mechanisms
      showed high levels of resistance to ACMV-CM, with viral DNA undetectable by PCR
      beyond 7days post inoculation (dpi). In contrast, all genotypes initially
      developed severe CMD symptoms and accumulated high virus titers after inoculation
      with EACMV KE2 (K201). Resistant genotypes recovered to become asymptomatic by
      65dpi with no detectable virus in newly formed leaves. Genotype TMS 97/2205
      showed highest resistance to EACMV KE2 (K201) with <30% of inoculated plants
      developing symptoms followed by complete recovery by 35dpi. Deep sequencing of
      small RNAs confirmed production of 21-24 nt virus derived small RNAs (vsRNA) that
      mapped to cover the entire ACMV-CM and EACMV KE2 (K201) viral genomes in both
      polarities, with hotspots seen within gene coding regions. In resistant
      genotypes, total vsRNAs were most abundant at 20 and 35dpi but reduced
      significantly upon recovery from CMD. In contrast, CMD susceptible genotypes
      displayed abundant vsRNAs throughout the experimental period. The percentage of
      vsRNAs reads ranked by class size were 21nt (45%), 22 nt (28%) and 24 nt (18%) in
      all genotypes studied. The number of vsRNA reads directly correlated with virus
      titer and CMD symptoms.

PMID- 27693921
TI  - Can the Functional Movement ScreenTM be used to capture changes in spine and knee
      motion control following 12 weeks of training?
AB  - OBJECTIVE: To examine whether objective measures of spine and frontal plane knee
      motion exhibited during Functional Movement ScreenTM (FMS) task performance
      changed following a movement-guided fitness (MOV) and conventional fitness (FIT)
      exercise intervention. DESIGN: Secondary analysis of a randomized controlled
      experiment. Before and after 12 weeks of exercise, participants' kinematics were
      quantified while performing the FMS and a series of general whole-body movement
      tasks. SETTING: Biomechanics laboratory. PARTICIPANTS: Fifty-two firefighters
      were assigned to MOV, FIT, or a control (CON) group. OUTCOME MEASURES: Peak
      lumbar spine flexion/extension, lateral bend and axial twist, and frontal plane
      knee motion. RESULTS: The post-training kinematic changes exhibited by trainees
      while performing the FMS tasks were similar in magnitude (effect size < 0.8) to
      those exhibited by CON. However, when performing the battery of general whole
      body movement tasks, only MOV showed significant improvements in spine and
      frontal plane knee motion control (effect size > 0.5). CONCLUSIONS: Whether
      graded qualitatively, or quantitatively via kinematic analyses, the FMS may not
      be a viable tool to detect movement-based exercise adaptations. Amendments to the
      FMS tasks and/or scoring method are needed before it can be used for reasons
      beyond appraising the ability to move freely, symmetrically, and without pain.

PMID- 27693922
TI  - Biological function analysis of monoclonal antibodies against human granulins in
      vitro using U251 cells as a model.
AB  - Progranulin (PGRN), a highly glycosylated, secreted 593 amino acid precursor
      protein, is a multifunctional molecule that is critical for early embryogenesis,
      wound repair, inflammatory and tumorigenesis. PGRN can be proteolytically cleaved
      into seven cysteine-rich granulin (Grn) peptides: G, F, B, A, C, D and E. Both
      PGRN and its constituent Grn peptides have been implicated in a wide variety of
      biological activities. However, their functions are far from clear, and the lack
      of granulin domain-specific antibodies has hindered the progress of the
      functional study of PGRN and Grns. Monoclonal antibodies against GrnB, GrnA, GrnC
      and GrnF have been previously developed by our laboratory. In this study, we
      generated monoclonal antibodies (MAbs) against GrnD, GrnG and GrnE by using
      recombinant proteins HSA-GrnG, HSA-GrnD and HSA-GrnE as immunogens, and
      characterized them by indirect ELISA, Western blot and immunocytochemistry.
      Furthermore, the neutralizing activities of the MAbs against seven Grns were
      tested in vitro using the U251 cell line. This full antibody panel of MAbs
      against seven Grns will be a valuable tool for elucidating the biological roles
      of PGRN and Grns in different physiopathological processes, which will further
      promote the development of PGRN-based clinical diagnosis and therapy.

PMID- 27693923
TI  - Potential health risk assessment of potato (Solanum tuberosum L.) grown on metal
      contaminated soils in the central zone of Punjab, Pakistan.
AB  - Metal buildup was estimated in potato (Solanum tuberosum L.), grown in central
      Punjab, Pakistan. This crop was irrigated with multiple water sources like
      ground, sewage and canal water. Concentrations of different metals like zinc
      (Zn), arsenic (As), lead (Pb), iron (Fe), nickel (Ni), molybdenum (Mo), copper
      (Cu), and selenium (Se) were assessed in the potato crop irrigated with different
      types of waters. Sewage water treated crop and soil had higher metal
      concentrations than those treated with other two treatments. All metals had
      positive and significant correlation except for Mo which was non-significantly
      correlated between the vegetable and soil. Highest daily intake was observed for
      Fe (0.267), whereas the lowest was seen for Se (0.003). The enrichment factor and
      health index varied between 0.135-15.08 and 0.285-83.77, respectively. This study
      concludes that vegetables cultivated on soil treated with sewage water is a
      potent threat for human health as the metals manifest toxicity after entering the
      food chain.

PMID- 27693924
TI  - Validation of a cage implant system for assessing in vivo performance of long
      acting release microspheres.
AB  - Here we describe development of a silicone rubber/stainless steel mesh cage
      implant system, much like that used to assess biocompatibility of biomaterials
      [1], for easy removal of injectable polymer microspheres in vivo. The sterile
      cage has a type 316 stainless steel mesh size (38 MUm) large enough for cell
      penetration and free fluid flow in vivo but small enough for microsphere
      retention, and a silicone rubber shell for injection of the microspheres. Two
      model drugs, the poorly soluble steroid, triamcinolone acetonide, and the highly
      water-soluble luteinizing hormone-releasing hormone (LHRH) peptide superagonist,
      leuprolide, were encapsulated in PLGA microspheres large enough (63-90 MUm) to be
      restrained by the cage implant in vivo. The in vitro release from both
      formulations was followed by ultra-performance liquid chromatography (UPLC) with
      and without the cage in a standard release media, PBS pH 7.4 + 0.02% Tween 80 +
      0.05% sodium azide, at 37  degrees C. Pharmacokinetics (PK) in rats was assessed
      after SC injection or SC in-cage implantation of microspheres with plasma
      analysis by LC-MS/MS or EIA. Tr-A and leuprolide in vitro release was largely
      unaffected after the initial burst irrespective of the cage or test tube
      incubation vessel and release was much slower than observed in vivo for both
      drugs. Moreover, Tr-A and leuprolide pharmacokinetics with and without the cage
      were highly similar during the 2-3 week release duration before a significant
      inflammatory response was caused by the cage implant. Hence, the PK-validated
      cage implant provides a simple means to recover and evaluate the microsphere drug
      carriers in vivo during a time window of at least a few weeks in order to
      characterize the polymer microsphere release and erosion behavior in vivo. This
      approach may facilitate development of mechanism-based in vitro/in vivo
      correlations and enable development of more accurate and useful in vitro release
      tests.

PMID- 27693925
TI  - Low serum prealbumin levels in post-stroke depression.
AB  - Previous studies have shown that prealbumin is associated with depression.
      However, the association between prealbumin and post-stroke depression remains
      unelucidated. This observational cohort study determined whether low baseline
      serum prealbumin could predict post-stroke depression at 1 month in patients
      admitted with acute stroke. The study, conducted from October 2013 to September
      2014, included 307 patients with acute stroke who were followed-up for 1 month.
      Serum prealbumin was measured within 24h after admission using an
      immunoturbidimetric method. The17-item Hamilton Depression Scale was used to
      evaluate depression symptoms. Patients with a depression score of >=7 were
      evaluated using the Structured Clinical Interview for Diagnostic and Statistical
      Manual of Mental Disorders, 4th edition, for diagnosing post-stroke depression at
      1 month. Binary logistic regression analysis was used to evaluate possible
      predictors of post-stroke depression. Overall, 93 (30.3%) patients were diagnosed
      with post-stroke depression. Serum prealbumin was significantly lower in patients
      with versus those without post-stroke depression, and was a significant predictor
      of post-stroke depression after adjusting for confounding risk factors. In
      conclusion, baseline serum prealbumin level was associated with post-stroke
      depression at 1 month, suggesting that prealbumin might be a useful biomarker for
      post-stroke depression.

PMID- 27693926
TI  - The genomic content and context of auxiliary metabolic genes in marine
      cyanomyoviruses.
AB  - Viruses of marine cyanobacteria frequently contain auxiliary metabolic genes
      (AMGs) that augment host metabolism during infection, but little is known about
      their adaptive significance. We analyzed the distribution and genomic context of
      33 AMGs across 60 cyanomyovirus genomes. Similarity in AMG content among
      cyanomyoviruses was only weakly correlated with phylogenetic relatedness;
      however, AMG content was generally conserved within the same operational
      taxonomic unit (OTU). A virus' AMG repertoire was also correlated with its
      isolation host and environment (coastal versus open ocean). A new analytical
      method based on shared co-linear blocks revealed that variation in the genomic
      location of an AMG was negatively correlated with its frequency across the
      genomes. We propose that rare AMGs are more frequently gained or lost as a result
      of fluctuating selection pressures, whereas common AMGs are associated with
      stable selection pressures. Finally, we describe a unique cyanomyovirus (S-CAM7)
      that lacks many AMGs including the photosynthesis gene psbA.

PMID- 27693927
TI  - The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related
      genes and augments cell self-renewal.
AB  - Oct3/4 is a transcription factor involved in maintenance of the pluripotency and
      self-renewal of stem cells. The E7 oncoprotein and 17beta-estradiol (E2) are key
      factors in cervical carcinogenesis. In the present study, we aimed to investigate
      the effect of the HPV16 E7 oncoprotein and E2 on the expression pattern of
      Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is
      associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog
      and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and
      implicate E2 in the upregulation of these factors in vivo. We also demonstrated
      that E7 is involved in cell self-renewal, suggesting that the HPV16 E7
      oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the
      self-renewal capacity of cancer stem cells.

PMID- 27693928
TI  - Neuropeptide modulation of pattern-generating systems in crustaceans: comparative
      studies and approaches.
AB  - Central pattern generators are subject to modulation by peptides, allowing for
      flexibility in patterned output. Current techniques used to characterize peptides
      include mass spectrometry and transcriptomics. In recent years, hundreds of
      neuropeptides have been sequenced from crustaceans; mass spectrometry has been
      used to identify peptides and to determine their levels and locations, setting
      the stage for comparative studies investigating the physiological roles of
      peptides. Such studies suggest that there is some evolutionary conservation of
      function, but also divergence of function even within a species. With current
      baseline data, it should be possible to begin using comparative approaches to ask
      fundamental questions about why peptides are encoded the way that they are and
      how this affects nervous system function.

PMID- 27693929
TI  - Diagnostic values of ProSet magnetic resonance coronal source imaging for
      detecting symptomatic lesion in multiple lumbar foraminal stenosis.
AB  - OBJECTIVE: The aim of this study is to evaluate the values of ProSet magnetic
      resonance coronal source imaging (ProSet MR imaging) as a diagnostic tool for
      detecting symptomatic lesion in patients with multiple lumbar foraminal stenosis.
      PATIENTS AND METHODS: From January 2011 to June 2015, 46 patients with unilateral
      and single-level radiculopathy developed from foraminal stenosis were enrolled in
      the study. These diagnoses were confirmed with transforaminal selective nerve
      root block (SNRB) and electrophysiological testing, including electromyography
      and nerve conduction velocity (EMG/NCV) tests. The detection of symptomatic
      lesion among multiple lumbar foraminal stenosis was done by identification of
      spinal nerve swelling (NS) and/or running course abnormalities (RCA) observed on
      ProSet MR imaging. These results were compared with those from transforaminal
      SNRB testing and conventional MR imaging. Evaluations were performed blinded by
      two independent examiners. RESULTS: The diagnostic accuracy rates of the two
      examiners were 84.7% and 82.6% with a 0.835 kappa coefficient. NS (80.4%) showed
      a higher diagnostic accuracy rate compared to RCA (69.6%) for detecting
      symptomatic lesion. The presence or absence of both NS and RCA has a stronger
      relationship with symptomatic or non-symptomatic lesion compared to the
      relationship of either alone (p=0.00). CONCLUSION: ProSet MR imaging is a simple
      and helpful method for providing additional diagnostic accuracy to detect
      symptomatic lesion in patients with multiple foraminal stenosis. NS representing
      chemical radiculitis was more reliable diagnostic factor of ProSet MR imaging.

PMID- 27693930
TI  - To what extent is alcohol consumption associated with breast cancer recurrence
      and second primary breast cancer?: A systematic review.
AB  - BACKGROUND: The association between alcohol intake and breast cancer recurrence
      or development of second primary breast cancer in the survivor population is
      unclear. The aim of this systematic review was to evaluate the existing evidence
      to assess the extent to which alcohol consumption is associated with breast
      cancer recurrence and second primary breast cancer. METHODS: Six databases
      (Cochrane Library, EMBASE, MEDLINE, PubMed, Scopus and Web of Science) were
      searched using the following search phrase: (breast cancer OR breast
      adenocarcinoma OR breast neoplasm OR breast tumour) AND (alcohol* OR alcohol
      intake OR alcohol consumption OR ethanol) AND (recurrence OR second primary). A
      narrative synthesis was conducted on studies meeting the inclusion criteria.
      RESULTS: After screening, 16 studies met the inclusion criteria, of which 11
      assessed breast cancer recurrence and 5 assessed second primary breast cancer.
      Considerable clinical and methodological heterogeneity was observed between
      studies. Approximately half of the included studies observed a modest, but
      significant, association between alcohol consumption and increased risk of breast
      cancer recurrence or development of a second primary breast cancer, with some
      studies observing associations from as little as six grams of alcohol intake per
      day. Two studies suggest this association was stronger in postmenopausal women.
      CONCLUSION: There is some evidence that alcohol consumption increases the risk of
      breast cancer recurrence, particularly in postmenopausal women. The association
      between alcohol and development of a second primary breast cancer is less clear.
      Inconsistencies in methodology and results across studies complicate attempts to
      develop a cohesive interpretation of findings.

PMID- 27693931
TI  - Mechanism of drug resistance in relation to site of metastasis: Meta-analyses of
      randomized controlled trials in advanced breast cancer according to anticancer
      strategy.
AB  - BACKGROUND: Breast cancer is heterogeneous at different levels: biologic
      subtypes, intratumoral areas, and sites of metastases. Randomized controlled
      trials (RCTs) classify metastatic sites as visceral or non-visceral, but this has
      little influence in treatment decisions, particularly in the absence of clinical
      urgency. Indeed, it is unclear if response to treatments differs among sites of
      metastases. PATIENTS AND METHODS: RCTs investigating 3 different anticancer
      strategies in metastatic breast cancer were identified: (1) new hormonal therapy,
      (2) new targeted therapies in hormone receptor positive tumours (everolimus or
      palbociclib), and (3) new anti-HER2 therapies. RCTs reporting hazard ratios (HR)
      for Progression Free Survival (PFS) and Overall Survival (OS) for sub-groups
      based on sites of metastases were weighted using generic inverse variance
      approach, and pooled in meta-analyses using Revman 5.3. Subgroup difference was
      tested with Chi2 statistics. RESULTS: Eleven RCTs (6701pts.) qualified. There was
      a significant difference in PFS between women with visceral versus non-visceral
      metastases when two endocrine strategies were compared, with benefits limited to
      women with visceral metastases [Pooled HR 0.85; 95% CI, 0.77-0.95 versus 1.02
      (0.88-1.18) for non-visceral; p(difference)=0.05]. However, combination of an
      endocrine therapy and a targeted therapy was associated with better PFS compared
      to endocrine therapy alone for both groups [HR 0.51 (0.43-0.60) versus 0.45 (0.36
      0.56) for non-visceral; p(difference)=0. 36]. Novel HER-2 targeted therapies were
      associated with significantly better PFS and OS only in visceral metastases [HR
      0.59 (0.52-0.66) versus 0.71(0.44-1.13) for non-visceral, p(difference)=0.45, for
      PFS; and 0.64 (0.56-0.73) versus 0.82 (0.57=1.19) for non-visceral,
      p(difference)=0.20, for OS]. CONCLUSION: Combination of targeted agents and
      endocrine therapy results in concordant, superior PFS suggesting targetable
      endocrine resistance across metastatic sites. Discordant responses with endocrine
      strategy alone support use of targeted therapy, rather than change in endocrine
      agent at disease progression. HER2 targeted therapies may be less effective in
      areas of poor vascularization.

PMID- 27693932
TI  - Biological effects of plasma rich in growth factors (PRGF) on human endometrial
      fibroblasts.
AB  - OBJECTIVES: To evaluate the biological outcomes of plasma rich in growth factors
      (PRGF) on human endometrial fibroblasts in culture. STUDY DESIGN: PRGF was
      obtained from three healthy donors and human endometrial fibroblasts (HEF) were
      isolated from endometrial specimens from five healthy women. The effects of PRGF
      on cell proliferation and migration, secretion of vascular endothelial growth
      factor (VEGF), procollagen type I and hyaluronic acid (HA) and contractility of
      isolated and cultured human endometrial fibroblasts (HEF) were analyzed.
      Statistical analysis was performed in order to compare the effects of PRGF with
      respect to control situation (T-test or Mann-Whitney U-test). RESULTS: We report
      a significantly elevated human endometrial fibroblast proliferation and migration
      after treatment with PRGF. In addition, stimulation of HEF with PRGF induced an
      increased expression of the angiogenic factor VEGF and favored the endometrial
      matrix remodeling by the secretion of procollagen type I and HA and endometrial
      regeneration by elevating the contractility of HEF. These results were obtained
      for all PRGF donors and each endometrial cell line. CONCLUSIONS: The myriad of
      growth factors contained in PRGF promoted HEF proliferation, migration and
      synthesis of paracrine molecules apart from increasing their contractility
      potential. These preliminary results suggest that PRGF improves the biological
      activity of HEF in vitro, enhancing the regulation of several cellular processes
      implied in endometrial regeneration. This innovative treatment deserves further
      investigation for its potential in "in vivo" endometrial development and
      especially in human embryo implantation.

PMID- 27693933
TI  - Comparison of systemic and local methotrexate treatments in cesarean scar
      pregnancies: time to change conventional treatment and follow-up protocols.
AB  - OBJECTIVE: The aim of this study was to compare the use of systemic and local
      methotrexate in the treatment of cesarean scar pregnancy. STUDY DESIGN: In this
      retrospective cohort study, we collected the data of 44 patients with cesarean
      scar pregnancy. The patients were grouped according to treatment modality: Group
      1, local methotrexate injection (n=17) and Group 2, systemic methotrexate (n=27).
      The groups were compared with respect to side effects, recovery time,
      reproductive outcome, and treatment cost. RESULTS: The mean gestational age at
      diagnosis (6.4+/-0.93 vs. 5.4+/-0.80 weeks, p=0.001), pretreatment serum beta
      human chorionic gonadotrophin level [27,970 (11,010-39,421) vs. 7606 (4725
      16,996) mIU/mL, p=0.001], and lesion size (2.74+/-1.36 and 1.28+/-0.55cm,
      p=0.001) were higher in Group 1. All patients were cured by primary therapy
      without additional surgery. The mean times for beta-human chorionic gonadotrophin
      normalization, the uterine-mass disappearance, were significantly shorter in
      Group 1 than in Group 2 (6.17+/-1.55 vs. 8.11+/-2.0 weeks, p=0.001 and 10.47+/
      4.14 vs. 13.40+/-4.44 weeks, p=0.002, respectively). The cost of treatment was
      similar between groups (281.133+/-112.123$ vs. 551.134+/-131.792$, p=0.76). The
      total pregnancy rates were not different between groups (5/16, 31.4% vs. 6/11,
      54.6%, p=0.301). One recurrent cesarean scar pregnancy occurred after systemic
      methotrexate. Oral ulcers, the most common side effect, were seen in seven
      patients in Group 2. CONCLUSION: Even though treatment success and reproductive
      outcomes are similar, local methotrexate is superior to systemic methotrexate
      with regard to recovery time, side effects, and treatment costs, even in patients
      with unfavorable pretreatment prognostic predictors.

PMID- 27693934
TI  - Cervical cancer screening after 50: near extinction?
AB  - OBJECTIVES: The objectives of this study were to determine the prevalence and
      predictors of Pap smear screening among women aged 50 years and older. STUDY
      DESIGN: This cross-sectional study was conducted at two large urban health
      centres in Selangor. A total of 515 women aged 50 and older were recruited.
      RESULTS: The mean age of the respondents was 58.83+/-7.05, with a range of 50- 83
      years. The prevalence of Pap smear screening was 39.22% (n=202). From the
      multivariate analysis, Pap smear screening was significantly associated with
      health care provider advice (adjusted odds ratio (AOR)=18.75; 95% CI=8.30,
      42.37); tertiary (AOR=11.26; 95% CI=1.50, 84.68) and secondary education level
      (AOR=9.47; 95% CI=1.43, 62.84); use of contraception (AOR=2.90; 95% CI=1.48,
      5.69); heart disease (AOR=0.22; 95% CI=0.05, 0.97); and worry about Pap smear
      results (AOR=0.20; 95% CI=0.09, 0.42). CONCLUSION: The prevalence of Pap smear
      screening in the older women is unsatisfactory. Health care provider advice,
      education level, use of contraception, heart disease and worry about Pap smear
      results were predictors of undergoing Pap smear screening in this study
      population.

PMID- 27693935
TI  - Distribution of female genital tract anomalies in two classifications.
AB  - OBJECTIVE: This study assessed the distribution of Mullerian duct anomalies in
      two verified classifications of female genital tract malformations, and the
      presence of associated renal defects. STUDY DESIGN: 621 women with confirmed
      female genital tract anomalies were retrospectively grouped under the European
      (ESHRE/ESGE) and the American (AFS) classification. The diagnosis of uterine
      malformation was based on findings in hysterosalpingography, two-dimensional
      ultrasonography, endoscopies, laparotomy, cesarean section and magnetic resonance
      imaging in 97.3% of cases. Renal status was determined in 378 patients, including
      5 with normal uterus and vagina. RESULTS: The European classification covered all
      621 women studied. Uterine anomalies without cervical or vaginal anomaly were
      found in 302 (48.6%) patients. Uterine anomaly was associated with vaginal
      anomaly in 45.2%, and vaginal anomaly alone was found in 26 (4.2%) cases. Septate
      uterus was the most common (49.1%) of all genital tract anomalies, followed by
      bicorporeal uteri (18.2%). The American classification covered 590 (95%) out of
      the 621 women with genital tract anomalies. The American system did not take into
      account vaginal anomalies in 170 (34.7%) and cervical anomalies in 174 (35.5%)
      out of 490 cases with uterine malformations. Renal abnormalities were found in 71
      (18.8%) out of 378 women, unilateral renal agenesis being the most common defect
      (12.2%), also found in 4 women without Mullerian duct anomaly. CONCLUSIONS: The
      European classification sufficiently covered uterine and vaginal abnormalities.
      The distribution of the main uterine anomalies was equal in both classifications.
      The American system missed cervical and vaginal anomalies associated with uterine
      anomalies. Evaluation of renal system is recommended for all patients with
      genital tract anomalies.

PMID- 27693936
TI  - Online health information on obesity in pregnancy: a systematic review.
AB  - OBJECTIVE: To assess the quality of health information available online for
      healthcare users on obesity in pregnancy and evaluate the role of the internet as
      an effective medium to advocate a healthy lifestyle in pregnancy. STUDY DESIGN:
      We used the poly-search engine Polymeta and complimented the results with Google
      searches (till July 2015) to identify relevant websites. All open access websites
      in English providing advice on the risks and management of obesity in pregnancy.
      Two independent reviewers assessed the quality of information provided in each of
      the included websites for credibility, accuracy, readability, content quality and
      technology. We compared websites 'quality according to their target population,
      health topic and source of funding'. RESULTS: Fifty-three websites were included.
      A third of websites were focused on obesity in pregnancy and two thirds targeted
      healthcare users. The median value for the overall credibility was 5/9, 7/12 for
      accuracy, 57.6/100 for readability, 45/80 for content quality and 75/100 for
      technology. Obesity specific websites provided lower credibility compared to
      general health websites (p=0.008). Websites targeting health users were easier to
      read (p=0.001). Non-governmental funded websites demonstrated higher content
      quality (p=0.005). Websites that are obesity focused, targeting health users and
      funded by non-governmental bodies demonstrated higher composite quality scores
      (p=0.048). CONCLUSIONS: Online information on obesity in pregnancy is varied.
      Governmental bodies in particular need to invest more efforts to improve the
      quality of online health information.

PMID- 27693937
TI  - Pelvic floor assessment after delivery: how should women be selected?
AB  - OBJECTIVE: Pelvic floor dysfunction after delivery is quite common. New mothers
      deserve to receive targeted care for pelvic floor dysfunction, but how should
      women who are at risk be identified and selected for treatment? This study
      investigated risk factors and puerperal health-seeking behaviours to develop a
      restrictive patient selection model for postpartum pelvic floor dysfunction
      assessment. STUDY DESIGN: This prospective observational study involved women who
      were at >=32 weeks gestational age when they delivered in a tertiary referral
      maternity hospital in Milan, Italy, between July and December 2014. Eligible
      women were scheduled for a 3-month postnatal pelvic floor clinic. The adherence
      rate to the pelvic floor clinic and the prevalence of pelvic floor dysfunctions
      at 3 months postpartum were recorded. Univariable and logistic multivariable
      analyses were performed to select risk factors for pelvic floor dysfunctions.
      Risk factors were then tested for sensitivity and specificity for 3-month
      postpartum pelvic floor dysfunctions. RESULTS: Of 1606 eligible women, 1293
      (80.5%) were included in the analysis; 685 puerperal women (53.0%) adhered to the
      3-month postnatal pelvic floor clinic; pelvic floor dysfunctions were detected in
      238 women (34.7%). Four elements emerged as risk factors: symptoms before
      pregnancy (OR 1.72, 95% CI 1.15-2.56; p=0.008), symptoms during pregnancy (OR
      2.13, 95% CI 1.49-3.06; p<0.0001), vacuum extractor use (OR 1.62, 95% CI 1.04
      2.54; p=0.034), and severe perineal tears (OR 19.45, 95% CI 2.42-156.15;
      p=0.005). The combined sensitivity and specificity for the 4 risk factors were
      82% and 39%, respectively. CONCLUSION: Internal risk factors analysis offers the
      potential to efficiently restrict patient selection for follow-up.

PMID- 27693938
TI  - Effect of IVF failure on quality of life and emotional status in infertile
      couples.
AB  - OBJECTIVE: To investigate the effect of a previous IVF failure on the quality of
      life and emotional distress, in couples undergoing IVF treatment. Experiencing
      IVF failure might cause differences on the anxiety-depression and quality of life
      scores of the couples, compared to the ones who were undergoing IVF treatment for
      the first time. STUDY DESIGN: This study included 64 couples who had previously
      experienced at least one IVF failure (Group 1) and 56 couples without history of
      IVF failure (Group 2) in a private Assisted Reproductive Center, Istanbul,
      Turkey. A sociodemographic data form, the FertiQoL International and Hospital
      Anxiety (HAD-A) and Depression scale (HAD-D) for evaluating the status of
      distress, were administered for the study. RESULT(S): FertiQoL scores were
      compared between the groups, the environment scale of the quality of life in
      treatment section was found to be significantly higher in Group 1 compared with
      Group 2 (p=0.009). The HAD-A and HAD-D scores did not differ significantly
      between the groups. Group-variables were investigated using multilevel analysis,
      the infertility duration and income level were found to have an effect on the
      subscales of quality of life (p=0.009 and p=0.001 respectively) in Group 2.
      Depression scores were higher in couples with infertility duration of below five
      years in Group 1 and Group 2 compared to couples with infertility duration of
      five years or above (MANOVA analysis). The level of education was found to affect
      the scores of HAD-D in Group 2, but not in Group 1 (p=0.011). The score of HAD-D
      was significantly affected by the family type only in Group 2 (p=0.009); the
      depression score of the couples living with a nuclear family was found to be
      higher compared with the couples living in a traditional family (p=0.021).
      CONCLUSION(S): Fertility-specific quality of life scores reveals better results
      regarding the orientation to the treatment environment in the couples with a
      previous IVF failure, compared to first IVF cycle couples. Treatment failure does
      not elevate the level of anxiety, while the effect on depression scores changes
      according to duration of infertility.

PMID- 27693939
TI  - Irreversible electroporation inhibits pro-cancer inflammatory signaling in triple
      negative breast cancer cells.
AB  - Low-level electric fields have been demonstrated to induce spatial re
      distribution of cell membrane receptors when applied for minutes or hours.
      However, there is limited literature on the influence on cell signaling with
      short transient high-amplitude pulses typically used in irreversible
      electroporation (IRE) for cancer treatment. Moreover, literature on signaling
      pertaining to immune cell trafficking after IRE is conflicting. We hypothesized
      that pulse parameters (field strength and exposure time) influence cell signaling
      and subsequently impact immune-cell trafficking. This hypothesis was tested in
      vitro on triple negative breast cancer cells treated with IRE, where the effects
      of pulse parameters on key cell signaling factors were investigated. Importantly,
      real time PCR mRNA measurements and ELISA protein analyses revealed that thymic
      stromal lymphopoietin (TSLP) signaling was down regulated by electric field
      strengths above a critical threshold, irrespective of exposure times spanning
      those typically used clinically. Comparison with other treatments (thermal shock,
      chemical poration, kinase inhibitors) revealed that IRE has a unique effect on
      TSLP. Because TSLP signaling has been demonstrated to drive pro-cancerous immune
      cell phenotypes in breast and pancreatic cancers, our finding motivates further
      investigation into the potential use of IRE for induction of an anti-tumor immune
      response in vivo.

PMID- 27693940
TI  - Effect of stimulus type and temperature on EEG reactivity in cardiac arrest.
AB  - OBJECTIVE: Electroencephalogram (EEG) background reactivity is a reliable outcome
      predictor in cardiac arrest patients post therapeutic hypothermia. However, there
      is no consensus on modality testing and prior studies reveal only fair to
      moderate agreement rates. The aim of this study was to explore different stimulus
      modalities and report interrater agreements. METHODS: We studied a multicenter,
      prospectively collected cohort of cardiac arrest patients who underwent
      therapeutic hypothermia between September 2014 and December 2015. We identified
      patients with reactivity data and evaluated interrater agreements of different
      stimulus modalities tested in hypothermia and normothermia. RESULTS: Of the 60
      patients studied, agreement rates were moderate to substantial during hypothermia
      and fair to moderate during normothermia. Bilateral nipple pressure is more
      sensitive (80%) when compared to other modalities in eliciting a reactive
      background in hypothermia. Auditory, nasal tickle, nailbed pressure and nipple
      pressure reactivity were associated with good outcomes in both hypothermia and
      normothermia. CONCLUSIONS: EEG reactivity varies depending on the stimulus
      testing modality as well as the temperature during which stimulation is
      performed, with nipple pressure emerging as the most sensitive during hypothermia
      for reactivity and outcome determination. SIGNIFICANCE: This highlights the
      importance of multiple stimulus testing modalities in EEG reactivity
      determination to reduce false negatives and optimize prognostication.

PMID- 27693942
TI  - Psych verbs, the linking problem, and the acquisition of language.
AB  - In acquiring language, children must learn to appropriately place the different
      participants of an event (e.g., causal agent, affected entity) into the correct
      syntactic positions (e.g., subject, object) so that listeners will know who did
      what to whom. While many of these mappings can be characterized by broad
      generalizations, both within and across languages (e.g., semantic agents tend to
      be mapped onto syntactic subjects), not all verbs fit neatly into these
      generalizations. One particularly striking example is verbs of psychological
      state: The experiencer of the state can appear as either the subject (Agnes
      fears/hates/loves Bartholomew) or the direct object (Agnes
      frightens/angers/delights Bartholomew). The present studies explore whether this
      apparent variability in subject/object mapping may actually result from
      differences in these verbs' underlying meanings. Specifically, we suggest that
      verbs like fear describe a habitual attitude towards some entity whereas verbs
      like frighten describe an externally caused emotional episode. We find that this
      distinction systematically characterizes verbs in English, Mandarin, and Korean.
      This pattern is generalized to novel verbs by adults in English, Japanese, and
      Russian, and even by English-speaking children who are just beginning to acquire
      psych verbs. This results support a broad role for systematic mappings between
      semantics and syntax in language acquisition.

PMID- 27693943
TI  - Synthesis and antiproliferative activity of peracetylated 2-amino-1,2-dideoxy-1
      nitro-d-glycero-l-manno and d-glycero-d-talo heptitols.
AB  - Michael additions between carbohydrate derived nitroalkenes and several aliphatic
      and aromatic amines proceeded in a stereoselective way, leading to peracetylated
      2-amino-1,2-dideoxy-1-nitro-heptitols. In addition, the antiproliferative
      activity of some of the new adducts has been studied. The results allowed to
      identify lead compounds which show GI50 values in the range 1.7-19MUM.

PMID- 27693944
TI  - In-vivo quantification of dynamic hip joint center errors and soft tissue
      artifact.
AB  - Hip joint center (HJC) measurement error can adversely affect predictions from
      biomechanical models. Soft tissue artifact (STA) may exacerbate HJC errors during
      dynamic motions. We quantified HJC error and the effect of STA in 11 young,
      asymptomatic adults during six activities. Subjects were imaged simultaneously
      with reflective skin markers (SM) and dual fluoroscopy (DF), an x-ray based
      technique with submillimeter accuracy that does not suffer from STA. Five HJCs
      were defined from locations of SM using three predictive (i.e., based on
      regression) and two functional methods; these calculations were repeated using
      the DF solutions. Hip joint center motion was analyzed during six degrees-of
      freedom (default) and three degrees-of-freedom hip joint kinematics. The position
      of the DF-measured femoral head center (FHC), served as the reference to
      calculate HJC error. The effect of STA was quantified with mean absolute
      deviation. HJC errors were (mean+/-SD) 16.6+/-8.4mm and 11.7+/-11.0mm using SM
      and DF solutions, respectively. HJC errors from SM measurements were all
      significantly different from the FHC in at least one anatomical direction during
      multiple activities. The mean absolute deviation of SM-based HJCs was 2.8+/
      0.7mm, which was greater than that for the FHC (0.6+/-0.1mm), suggesting that STA
      caused approximately 2.2mm of spurious HJC motion. Constraining the hip joint to
      three degrees-of-freedom led to approximately 3.1mm of spurious HJC motion. Our
      results indicate that STA-induced motion of the HJC contributes to the overall
      error, but inaccuracies inherent with predictive and functional methods appear to
      be a larger source of error.

PMID- 27693945
TI  - Repair genes expression profile of MLH1, MSH2 and ATM in the normal oral mucosa
      of chronic smokers.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of chronic smoking on
      the expression profile of the repair genes MLH1, MSH2 and ATM in the normal oral
      mucosa of chronic smokers and never smokers. MATERIALS AND METHODS: The sample
      consisted of thirty exfoliative cytology smears per group obtained from Smokers
      and Never Smokers. Total RNA was extracted and expression of the MLH1, MSH2 and
      ATM genes were evaluated by quantitative real-time and immunocytochemistry. The
      gene and protein expression data were correlated to the clinical data. Gene
      expression was analyzed statistically using the Student t-test and Pearson's
      correlation coefficient, with p<0.05. RESULTS: MLH1, MSH2 and ATM genes were
      downregulated in the smoking group compared to the control with significant
      values for MLH1 (p=0.006), MSH2 (p=0.0001) and ATM (p=0.0001). Immunocytochemical
      staining for anti-MLH1, anti-MSH2 and anti-ATM was negative in Never Smokers; in
      Smokers it was rarely positive. No significant correlation was observed among the
      expression of MLH1, MSH2, ATM and age, number of cigarettes consumed per day,
      time of smoking during life, smoking history or levels of CO in expired air.
      CONCLUSION: The expression of genes and proteins related to DNA repair mechanism
      MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers was reduced.

PMID- 27693941
TI  - Animal models of transcranial direct current stimulation: Methods and mechanisms.
AB  - The objective of this review is to summarize the contribution of animal research
      using direct current stimulation (DCS) to our understanding of the physiological
      effects of transcranial direct current stimulation (tDCS). We comprehensively
      address experimental methodology in animal studies, broadly classified as: (1)
      transcranial stimulation; (2) direct cortical stimulation in vivo and (3) in
      vitro models. In each case advantages and disadvantages for translational
      research are discussed including dose translation and the overarching "quasi
      uniform" assumption, which underpins translational relevance in all animal models
      of tDCS. Terminology such as anode, cathode, inward current, outward current,
      current density, electric field, and uniform are defined. Though we put key
      animal experiments spanning decades in perspective, our goal is not simply an
      exhaustive cataloging of relevant animal studies, but rather to put them in
      context of ongoing efforts to improve tDCS. Cellular targets, including
      excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and
      endothelial cells are considered. We emphasize neurons are always depolarized and
      hyperpolarized such that effects of DCS on neuronal excitability can only be
      evaluated within subcellular regions of the neuron. Findings from animal studies
      on the effects of DCS on plasticity (LTP/LTD) and network oscillations are
      reviewed extensively. Any endogenous phenomena dependent on membrane potential
      changes are, in theory, susceptible to modulation by DCS. The relevance of
      morphological changes (galvanotropy) to tDCS is also considered, as we suggest
      microscopic migration of axon terminals or dendritic spines may be relevant
      during tDCS. A majority of clinical studies using tDCS employ a simplistic dose
      strategy where excitability is singularly increased or decreased under the anode
      and cathode, respectively. We discuss how this strategy, itself based on classic
      animal studies, cannot account for the complexity of normal and pathological
      brain function, and how recent studies have already indicated more sophisticated
      approaches are necessary. One tDCS theory regarding "functional targeting"
      suggests the specificity of tDCS effects are possible by modulating ongoing
      function (plasticity). Use of animal models of disease are summarized including
      pain, movement disorders, stroke, and epilepsy.

PMID- 27693946
TI  - Near-infrared light-triggered release of small molecules for controlled
      differentiation and long-term tracking of stem cells in vivo using upconversion
      nanoparticles.
AB  - Human mesenchymal stem cells (hMSCs) hold considerable potential for regenerative
      medicine, but their application is limited by the lack of an efficient method to
      control differentiation and track the migration of implanted cells in vivo. In
      this study, we developed a multifunctional nanocarrier based on upconversion
      nanoparticles (UCNPs) for controlling differentiation and long-term tracking of
      hMSCs. The UCNPs are conjugated with the peptide (Cys-Arg-Gly-Asp, CRGD) and the
      differentiation-inducing kartogenin (KGN) via a photocaged linker on the surface,
      and the obtained UCNP nanocarrier can be efficiently uptaken by hMSCs. Under the
      exposure of near-infrared (NIR) light, the upconverted UV emission from the UCNP
      nanocarrier leads to the photocleavage of the photocaged linker and intracellular
      release of KGN. The NIR-triggered release of KGN mediated by the UCNP nanocarrier
      efficiently induces chondrogenic differentiation of hMSCs in vitro with reduced
      KGN dosage compared to the conventional protocol of directly supplementing KGN in
      the media. Furthermore, NIR irradiation through the skin of living animals
      induces the chondrogenic differentiation of the subcutaneously implanted hMSCs
      treated with the KGN-laden UCNP nanocarrier, thereby enhancing neocartilage
      formation in vivo. Finally, the luminescent UCNP nanocarrier enables the long
      term tracking of the labeled hMSCs in vivo. We believe that our UCNP nanocarrier
      is a promising tool for the remote control of triggered delivery of inductive
      agents to stem cells at the prescribed time points and the elucidation of the
      function and the fate of the transplanted stem cells in vivo.

PMID- 27693947
TI  - Identification of non-resistant ROS-1 inhibitors using structure based
      pharmacophore analysis.
AB  - Proto-oncogene receptor tyrosine kinase ROS-1 plays a key role in regulating a
      variety of cancers mainly non-small cell lung cancer (NSCLC). The marketed ROS-1
      inhibitors such as Crizotinib suffer from the tribulations of growing resistance
      due to mutations primarily Gly2032Arg in the ROS-1 protein. To curb the problem
      of resistance, researchers have developed inhibitors such as Lorlatinib against
      the mutant protein. The present study was designed to identify inhibitors against
      wild type (WT) as well as mutant ROS-1 protein that will offer a broader spectrum
      of activity. Exploring crystal structure of ROS-1 complexed with Lorlatinib,
      receptor-ligand pharmacophore model was developed using Discovery Studio (DS)
      software. The developed pharmacophore model consisted of one hydrogen bond
      acceptor (HBA), one hydrogen bond donor (HBD) and two hydrophobic features (HY),
      subsequently utilized for virtual screening of commercially available databases
      and the retrieved hits were further subjected to fitness score and Lipinski's
      filter. Thereafter, the retrieved hits were docked in WT and mutated (Gly2032Arg)
      proteins of ROS-1. Total five molecules were retrieved with good docking scores
      and good binding interactions within the active site of WT and mutated ROS-1. The
      binding energies of the ligand-receptor complexes were predicted via calculation
      of MM-GBSA score. To predict the stability of the ligand receptor complexes with
      mutant and wild type proteins, molecular dynamic simulation was performed. Thus,
      these identified hits show good binding affinities with WT and mutant ROS-1
      proteins that may be further evaluated for their in-vitro/in-vivo activity.

PMID- 27693948
TI  - Molecular simulation study on concentration effects of rofecoxib with POPC
      bilayer.
AB  - The interactions between rofecoxib and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine) bilayer were studied using all-atom molecular dynamics simulation
      method. Four POPC bilayer systems with different number of rofecoxib molecules
      were constructed to simulate different drug concentration. The free energy of
      rofecoxib passing across pure POPC bilayer has two minima (at z ~1.2nm or 1.6nm).
      As for the high concentration model, the minimum of the free energy profile
      slightly shifts to the bilayer center. Moreover, the energy change from bulk
      water to POPC bilayer increases while the central barrier to cross the
      hydrophobic core of bilayer slightly decreases, suggesting that increasing drug
      concentration makes it favorable for rofecoxib to partition into the bilayer and
      easier to pass across bialyer center. Energy analysis show that the stabilization
      between the selected rofecoxib and other pre-inserted rofecoxib molecule is
      mainly due to van der Waals interaction energy. The predicted permeability of
      rofecoxib in high concentration model slightly weakens as compared with low
      concentration model.

PMID- 27693949
TI  - Persons with latent autoimmune diabetes in adults express higher dipeptidyl
      peptidase-4 activity compared to persons with type 2 and type 1 diabetes.
AB  - AIMS: We aimed to determine serum dipeptidyl peptidase-4 (DPP-4) activity in a
      group of persons with latent autoimmune diabetes in adults (LADA) and to compare
      it with persons with type 1, type 2 diabetes and healthy controls. METHODS: DPP-4
      activity measurement was performed in 67 persons (21 with type 1, 26 type 2 and
      19 with LADA) and 13 healthy age and gender matched controls. RESULTS: Persons
      with LADA showed highest DPP-4 activity among the study groups (32.71+/-3.55 vs
      25.37+/-2.84 vs 18.57+/-2.54 vs 18.57+/-2.61U/L p<0.001). Mean glutamic acid
      autoantibody in persons with LADA was 164.32+/-86.28IU/mL. It correlated with DPP
      4 activity (r=0.484, p=0.013). Furthermore, DPP-4 activity correlated with waist
      circumference (r=0.279, p=0.034) and glycated haemoglobin A1c (r=0.483, p<0.001),
      as well as with LDL cholesterol (r=0.854, p<0.001) and total daily insulin dose
      (r=0.397, p=0.001). In the multinomial regression analysis DPP-4 activity
      remained associated with both LADA (prevalence ratio 1.058 (1.012-1.287),
      p=0.001) and type 1 diabetes (prevalence ratio 1.506 (1.335-1.765), p<0.001)
      while it did not show an association with type 2 diabetes (prevalence ratio 0.942
      (0.713-1.988), p=0.564). CONCLUSIONS: Persons with LADA express higher DPP-4
      activity compared to persons with both type 1 and type 2 diabetes. The possible
      pathophysiological role of DPP-4 in the LADA pathogenesis needs to be further
      evaluated.

PMID- 27693950
TI  - Blood-based immune-endocrine biomarkers of treatment response in depression.
AB  - Antidepressant treatment for major depressive disorder remains suboptimal with
      response rates of just over 50%. Although treatment guidelines, algorithms and
      clinical keys are available to assist the clinician, the process of finding an
      effective pharmacotherapy to maximise benefit for the individual patient is
      largely by "trial and error" and remains challenging. This highlights a clear
      need to identify biomarkers of treatment response to help guide personalised
      treatment strategies. We have carried out the largest multiplex immunoassay based
      longitudinal study to date, examining up to 258 serum markers involved in immune,
      endocrine and metabolic processes as potential biomarkers associated with
      treatment response in 332 depression patients recruited from four independent
      clinical centres. We demonstrated for the first time that circulating
      Apolipoprotein A-IV, Endoglin, Intercellular Adhesion Molecule 1, Tissue
      Inhibitor of Metalloproteinases 1, Plasminogen Activator Inhibitor 1,
      Thrombopoietin, Complement C3, Hepatocyte Growth Factor and Insulin-like Growth
      Factor-Binding Protein 2 were associated with response to different
      antidepressants. In addition, we showed that specific sets of immune-endocrine
      proteins were associated with response to Venlafaxine (serotonin-norepinephrine
      reuptake inhibitor), Imipramine (tricyclic antidepressant) and other
      antidepressant drugs. However, we were not able to reproduce the literature
      findings on BDNF and TNF-alpha, two of the most commonly reported candidate
      treatment response markers. Despite the need for extensive validation studies,
      our preliminary findings suggest that a pre-treatment immune-endocrine profile
      may help to determine a patient's likelihood to respond to specific
      antidepressant and/or alternative treatments such as anti-inflammatory drugs,
      providing hope for future personalised treatment approaches.

PMID- 27693951
TI  - Quality assessment of marketed chamomile tea products by a validated HPTLC method
      combined with multivariate analysis.
AB  - Chamomile tea composed of dried flower heads of Matricaria recutita L.
      (Asteraceae) is one of the most popular single ingredient herbal teas. Tea
      industries, spice shops or public bazaars are mostly supplied chamomile as a raw
      material via cultivation or through nature-picking. However, one of the drawbacks
      of nature-picking is adulteration. This could be either due to false
      authentication of the plant materials by ingenuous pickers or
      intentional/unintentional substitution with other flowers resembling to chamomile
      in appearance during harvesting. Therefore, quality control of raw chamomile
      materials before marketing should be carefully considered not only by
      quantification of apigenin 7-O-glucoside (active marker) but also by
      fingerprinting of chemical composition. This work presents both quantification of
      apigenin 7-O-glucoside and chemical fingerprinting of commercial chamomile tea
      products obtained from different food stores and spice shops by a validated HPTLC
      method. In addition, HPTLC profiles of investigated chamomile tea samples were
      compared with HPLC method stated in the European Pharmacopoeia and it was found
      that HPTLC method was superior to HPLC method in the field of adulteration
      confirmation. Therefore, fingerprint profiles performed on the silica gel 60 NH2
      F254s HPTLC plates combined with pattern recognition techniques of these marketed
      products were comparatively evaluated with wild and cultivar chamomile samples
      and also chamomile-like species from Asteraceae. Consequently, not chamomile tea
      bags but crude flowers sold on market were found to be adulterated with other
      plant materials.

PMID- 27693952
TI  - Simultaneous quantification and identification of flavonoids, lignans, coumarin
      and amides in leaves of Zanthoxylum armatum using UPLC-DAD-ESI-QTOF-MS/MS.
AB  - The current study presents isolation and characterization of twelve compounds
      including catechin (1), isovitexin (2), hesperidin (3), psoralin (4), eudesmin
      (5), kobusin (6), fargesin (7), sesamin (8), asarinin (9), planispine-A (10),
      alpha-sanshool (11) and vitexin (12), from the leaves of Zanthoxylum armatum.
      Further, two rapid and simple ultra performance liquid chromatography-diode array
      detection (UPLC-DAD) methods were developed for the simultaneous quantitative
      determination of isolated compounds from Z. armatum leaves. These analytical
      methods were validated for linearity, precision, accuracy, limit of detection
      (LOD) and limit of quantification (LOQ). The LOD and LOQ were in the range of
      0.06-0.21MUg/mL and 0.19-0.69MUg/mL, respectively. The validated method was
      linear (R2>=0.9906), precise in terms of peak area (intra-day RSDs <3.8% and
      inter-day RSDs <2.7%), and accurate (109.6-92.5%). This is the first report on
      the isolation and quantification of 1, 2, 4 and 12 in Z. armatum and 3 in
      Zanthoxylum genus. The methods: were successfully applied to assess the quality
      of samples collected from different locations of Himachal Pradesh during summer
      and winter season. The results demonstrated that flavonoids and furofuran lignans
      were the major constituents in Z. armatum leaves. The developed methods: were
      further applied for tandem electrospray ionization-mass spectrometry (UPLC-DAD
      ESI-MS/MS) and total eighteen compounds were identified including phenolic acid,
      flavonoids, furofuran lignans, coumarin and isobutyl amides.

PMID- 27693953
TI  - Quantitative determination of xanthorrhizol in rat plasma by HPLC-MS/MS and its
      application to a pharmacokinetic study.
AB  - Although xanthorrhizol, a sesquiterpenoid oil isolated from the rhizoma of
      Curcuma xanthorrhiza Roxb. known as Java turmeric, represents a variety of
      pharmacological activities, to date, there have been no validated determination
      methods of xanthorrhizol in biological samples. Thus, we developed a liquid
      chromatographic method using a tandem mass spectrometry for the determination of
      xanthorrhizol in rat plasma. After simple protein precipitation with acetonitrile
      including diclofenac (internal standard, IS), the analytes were chromatographed
      on a reversed-phased column with a mobile phase of 20mM ammonium acetate aqueous
      solution and acetonitrile (20:80, v/v). The ion transitions of the precursor to
      the product ion were principally deprotonated ions [M-H]- at m/z 216.9->132.8 for
      xanthorrhizol and 296.1->251.7 for the IS. The accuracy and precision of the
      assay were in accordance with FDA regulations for the validation of bioanalytical
      methods. This analytical method was successfully applied to monitor plasma
      concentrations of xanthorrhizol over time following intravenous administration in
      rats.

PMID- 27693954
TI  - Study the influence of licorice and pomegranate drinks on nicotine metabolism in
      human urine by LC-orbitrap MS.
AB  - Nicotine-diet interactions have a particular importance on human health. Some
      food substances are subject to change hepatic CYP2A6 metabolism rate for nicotine
      and its levels in smokers consequently. This study investigates the effect of
      pomegranate and licorice drinks on nicotine metabolism, by a new developed and
      validated method for simultaneous determination of nicotine with its major
      metabolites (cotinine and nicotine N-oxide) in human urine, utilizing LC ESI
      orbitrap-MS. Twenty-four Jordanian healthy and smoker volunteers were
      participated in two equal groups, crossover design for each of pomegranate and
      licorice test drink. In the study periods each group assigned either to drink
      test juice three times a day or to be avoided from test drink for 7 successive
      days, and then both groups switched their drink treatment in subsequent period.
      Early morning urine samples were collected from all volunteers after each period.
      Nicotine metabolism rate was evaluated from nicotine/cotinine and
      nicotine/nicotine N-oxide ratios in urine. A consistent trend of increase in
      metabolism rate for nicotine was observed from urine analysis under pomegranate
      or licorice drink conditions compared to control conditions. Pomegranate and
      licorice drinks are increasing the metabolism rate for nicotine in terms of
      induction effect for hepatic cytochrome p450 enzymes.

PMID- 27693955
TI  - Four-way-leaning test shows larger limits of stability than a circular-leaning
      test.
AB  - INTRODUCTION: Limits of stability (LOS) have extensive clinical and
      rehabilitational value yet no standard consensus on measuring LOS exists. LOS
      measured using a leaning or a circling protocol is commonly used in research and
      clinical settings, however differences in protocols and reliability problems
      exist. OBJECTIVE: This study measured LOS using a four-way-leaning test and a
      circular-leaning test to test which showed larger LOS measurements. Furthermore,
      number of adaptation trials needed for consistent results was assessed. METHOD:
      Limits of stability were measured using a force plate (Metitur Good Balance
      System(r)) sampling at 50Hz. Thirty healthy subjects completed 30 trials
      assessing LOS alternating between four-way-leaning test and circular-leaning
      test. RESULTS: A main effect of methods (ANOVA:F(1,28)=45.86, P<0.01) with the
      four-way-leaning test showing larger values than the circular-leaning test (NK,
      P<0.01). An interaction between method*directions was found (ANOVA:F(3,
      84)=24.87, P<0.01). The four-way-leaning test showed larger LOS in anterior (NK,
      P<0.05), right (NK, P<0.01) and left direction (NK, P<0.01). Analysis of LOS for
      the four-way-leaning test showed a difference between trials
      (ANOVA:F(14,392)=7.81, P<0.01). Differences were found between trial 1 and 7 (NK,
      P<0.03), trial 6 and 8 (NK, P<0.02) and trial 7 and 15 (NK, P<0.02). Four-way
      leaning test showed high correlation (ICC>0.87) between first and second trial
      for all directions. CONCLUSION: Four-way-leaning test yields larger LOS in
      anterior, right and left direction making it more reliable when measuring LOS. A
      learning effect was found up to the 8th trial, which suggests using 8 adaptation
      trials before reliable LOS is measured.

PMID- 27693957
TI  - Inter-session agreement and reliability of the Global Gait Asymmetry index in
      healthy adults.
AB  - There has been a growing effort in restoring gait symmetry in clinical conditions
      associated with pronounced gait asymmetry. A prerequisite to achieve this is that
      the chosen approach can accurately assess symmetry and detect/impose changes that
      exceed the natural day to day variability. Global symmetry indices are superior
      to local and discrete indices because they capture the patient's overall gait
      symmetry. However, their repeatability is unknown. This study assessed the inter
      session agreement and reliability of the Global Gait Asymmetry index. Twenty
      three healthy individuals participated in two 3D gait analyses, performed
      approximately one week apart. The 95% limits of agreement, standard error of
      measurement, smallest detectable change, and intraclass correlation coefficient
      were analysed. The obtained values showed this index has poor agreement and
      reliability between sessions. Therefore, it cannot be used to assess the
      patient's progress overtime nor to compare symmetry levels among groups.

PMID- 27693956
TI  - Validation of a commercial inertial sensor system for spatiotemporal gait
      measurements in children.
AB  - Although inertial sensor systems are becoming a popular tool for gait analysis in
      both healthy and pathological adult populations, there are currently no data on
      the validity of these systems for use with children. The purpose of this study
      was to validate spatiotemporal data from a commercial inertial sensor system
      (MobilityLab) in typically-developing children. Data from 10 children (5 males;
      3.0-8.3 years, mean=5.1) were collected simultaneously from MobilityLab and 3D
      motion capture during gait at self-selected and fast walking speeds.
      Spatiotemporal parameters were compared between the two methods using a Bland
      Altman method. The results indicate that, while the temporal gait measurements
      were similar between the two systems, MobilityLab demonstrated a consistent bias
      with respect to measurement of the spatial data (stride length). This error is
      likely due to differences in relative leg length and gait characteristics in
      children compared to the MobilityLab adult reference population used to develop
      the stride length algorithm. A regression-based equation was developed based on
      the current data to correct the MobilityLab stride length output. The correction
      was based on leg length, stride time, and shank range-of-motion, each of which
      were independently associated with stride length. Once the correction was
      applied, all of the spatiotemporal parameters evaluated showed good agreement.
      The results of this study indicate that MobilityLab is a valid tool for gait
      analysis in typically-developing children. Further research is needed to
      determine the efficacy of this system for use in children suffering from
      pathologies that impact gait mechanics.

PMID- 27693958
TI  - Gait deficits in people with multiple sclerosis: A systematic review and meta
      analysis.
AB  - BACKGROUND: Multiple Sclerosis (MS) results in postural instability and gait
      abnormalities which are associated with accidental falls. OBJECTIVE: This
      systematic review and meta-analysis aims to quantify the effect of MS on gait to
      inform the development of falls prevention interventions. METHODS: A systematic
      literature search identified case-control studies investigating differences in
      gait variables between people with MS and healthy controls. Meta-analysis
      examined the effect of MS on gait under normal and fast paced conditions.
      RESULTS: Forty-one studies of people with Expanded Disability Status Scale (EDSS)
      1.8 to 4.5 were included, of which 32 contributed to meta-analysis. A large
      effect of MS was found on stride length (Standardised Mean Difference, SMD=1.27,
      95% CI{0.93, 1.61}), velocity (SMD=1.12, 95% CI{0.85, 1.39}), double support
      duration (SMD=0.85, 95% CI{0.51, 1.2}), step length (SMD=1.15, 95% CI{0.75,
      1.5})and swing phase duration (SMD=1.23, 95% CI{0.06, 2.41}). A moderate effect
      was found on step width and stride time with the smallest effect found on cadence
      (SMD=0.43, 95% CI{0.14, 0.72}). All effect sizes increased for variables
      investigated under a fast walking pace condition (for example the effect on
      cadence increased to SMD=1.15, 95% CI{0.42, 1.88}). CONCLUSIONS: MS has a
      significant effect on gait even for those with relatively low EDSS. This effect
      is amplified when walking at faster speeds suggesting this condition may be more
      beneficial for assessment and treatment. No studies investigated the association
      between these deficits and falls. Further investigation relating to the
      predictive or protective nature of these deficits in relation to falls is
      warranted.

PMID- 27693960
TI  - Molecular characterization of Toxoplasma gondii in pork meat from different
      production systems in the Czech Republic.
AB  - Toxoplasmosis is a major public health issue, due to the presence of Toxoplasma
      gondii, mainly in pork. The aim of this study was to determine the occurrence of
      T. gondii in pigs and wild boars bred in different production systems in the
      Czech Republic using ELISA and qPCR methods. Our results show that T. gondii
      infection is widespread in pigs and wild boars bred and slaughtered in the Czech
      Republic and that there is a higher exposure to T. gondii in backyard slaughter
      operations and organic pig farming, indicating a potential risk for meat
      consumption. Additionally, genotyping of amplified loci for Type II suggests the
      presence of one clonal genotype circulating in these animals.

PMID- 27693959
TI  - Long-term effects of lateral wedge orthotics on hip and ankle joint space widths.
AB  - BACKGROUND: Lateral wedge insoles have been used for the treatment of medial knee
      osteoarthritis (OA) and have been shown to reduce loading of the medial
      compartment of the knee. However, as the entire lower extremity acts as a single
      kinetic chain, altering the biomechanics of the knee may also have significant
      effects at the ankles or hips. We aimed to evaluate the effects of lateral wedge
      orthotics on ankle and hip joints, compared to neutral orthotics, by assessing
      the changes in joint space width (JSW) during 36 months of continuous use.
      METHODS: We prospectively enrolled 109 subjects with symptomatic osteoarthritis
      of the medial knee according to the American College of Rheumatology criteria.
      The trial was double blind and patients were randomized to either wedged or
      neutral orthotic shoe inserts. Hip and ankle JSWs were quantified using plain
      radiographies at baseline and at 36-months follow-up. FINDINGS: 45 patients
      completed the 36 month study. 31 of those who completed the study were using the
      lateral wedge versus 14 were using neutral orthotics. 2 patients in the wedge
      group had missing radiographs and were not included in the JSW analyses. There
      were no significant differences between the wedge and the neutral orthotics
      groups in the magnitude of JSW change at either the hip or the ankles at 36
      month. INTERPRETATION: We found no significant adverse effects of the lateral
      wedges on ankles or hips. (ClinicalTrials.gov NCT00076453).

PMID- 27693962
TI  - Effects of activin A and its downstream ERK1/2 in oxygen and glucose deprivation
      after isoflurane-induced postconditioning.
AB  - BACKGROUND: Isoflurane postconditioning (ISPOC) plays a neuroprotection role in
      the brain. Previous studies confirmed that isoflurane postconditioning can
      provide better protection than preconditioning in acute hypoxic-ischemic brain
      damage, such as acute craniocerebral trauma and ischemic stroke. Numerous studies
      have reported that activin A can protect rat's brain from cell injury. However,
      whether activin A and its downstream ERK1/2 were involved in isoflurane
      postconditioning-induced neuroprotection is unknown. METHODS: A total of 80
      healthy Sprague-Dawley rats weighing 50-70g were randomly divided into 10 groups
      of 8: normal control, oxygen and glucose deprivation (OGD), 1.5% ISPOC, 3.0%
      ISPOC, 4.5% ISPOC, blocker of activin A (SB431542), blocker of ERK1/2 (U0126),
      3.0% ISPOC+SB431542, 3.0% ISPOC+U0126, and vehicle (dimethyl sulfoxide(DMSO))
      group. Blockers (SB431542 and U0126) were used in each concentration of
      isoflurane before OGD. Hematoxylin-eosin staining, 2,3,5-triphenyl tetrazolium
      chloride staining, and propidium iodide (PI) staining were conducted to assess
      the reliability in the brain slices. Immunofluorescence, Western blot, and
      quantitative real-time PCR(Q-PCR) were performed to validate the protein
      expression levels of activin A, Smad2/3, P-Smad2/3, ERK1/2, and phosphorylation
      ERK1/2 (P-ERK1/2). RESULTS: The number of damaged neurons and mean fluorescence
      intensity(MFI) of PI staining increased, but formazan generation, expression
      levels of activin A and P-ERK1/2 protein, and mRNA synthesis level of activin A
      decreased in the OGD group compared with the normal control group (p<0.05). The
      number of damaged neurons and MFI of PI staining decreased, but formazan
      production, expression levels of activin A, P-Smad2/3, and P-ERK1/2, and mRNA
      synthesis level of activin A increased significantly in the 1.5% ISPOC and 3.0%
      ISPOC groups (p<0.05) compared with the OGD group. The result in the 4.5% ISPOC
      group, was completely opposite to the 1.5% ISPOC and 3.0% ISPOC groups. The
      number of damage neuron and MFI of PI staining increased, but formazan
      production, expression levels of activin A, P-Smad2/3, and P-ERK1/2, and mRNA
      synthesis level of activin A decreased in the 4.5% ISPOC group. However, the
      expression levels of activin A, P-Smad2/3, and P-ERK1/2, and mRNA synthesis level
      of activin A in the 4.5% ISPOC group were higher than the OGD group (p<0.05). The
      other results were compared between the SB431542 group/the U0126 group and 3.0%
      ISPOC group. The MFI of PI staining increased, but the expression levels of
      activin A, P-Smad2/3, and P-ERK1/2 decreased (p<0.05). The expression level of
      ERK1/2 protein in all groups exhibited no change (p>0.05). CONCLUSION: Results of
      this study showed that 3.0% concentration of isoflurane postconditioning provided
      better neuroprotection than 1.5% and 4.5% concentrations of isoflurane. Activin
      A/Smad 2/3 and activin A/ERK1/2 signaling pathway may be involved in ISPOC
      induced neuroprotection.

PMID- 27693963
TI  - High glucose prevents osteogenic differentiation of mesenchymal stem cells via
      lncRNA AK028326/CXCL13 pathway.
AB  - BACKGROUND: High glucose (HG) often induces unfavorable effects on proliferation
      and differentiation of mesenchymal stem cells (MSCs). This study aimed to explore
      potential molecular pathways underlying HG functional mechanism during osteogenic
      differentiation of MSCs, involving lncRNA AK028326 and CXCL13. METHODS: Murine
      bone marrow-derived MSCs were cultured in osteogenic-inducing medium supplemented
      with high glucose level at 25mM or 5.5mM as normal control. Expression levels of
      lncRNA AK028326 and CXCL13 were measured by using real-time PCR. The mineralized
      nodule formation and alkaline phosphatase (ALP) activity were detected after 21
      and 7days of incubation respectively. Western blot were also performed to
      determine the expression of CXCL13 and osteogenic gene markers. Plasmid pcDNAs
      and small interference RNAs were transfected as indicated for functional analysis
      of AK028326 and CXCL13. RESULTS: HG suppressed the expression of AK028326 and
      CXCL13 in MSCs in a time-dependent manner, and also the mineralization, ALP
      activity, and osteogenic gene expression, which could be reversed by
      overexpression of AK028326 or CXCL13. CXCL13 expression was positively regulated
      by AK028326 at both mRNA and protein levels. Moreover, CXCL13 mediated the
      positive regulation of AK028326 on osteogenic gene expression in MSCs and MC3T3
      E1 cells, mineralization and ALP activity in MSCs and also HG-induced inhibitory
      effects during MSCs differentiation into osteoblast. CONCLUSION: HG could inhibit
      osteogenic differentiation of MSCs via inhibited expression of CXCL13 mediated by
      lncRNA AK028326, thereby providing new insights into the molecular mechanism of
      many osteogenesis-related diseases especially for patients with hyperglycemia.

PMID- 27693961
TI  - Molecular and cellular effects of vitamin B12 forms on human trophoblast cells in
      presence of excessive folate.
AB  - Folic acid (FA) and iron are essential supplements during pregnancy. Similarly
      effects of vitamin B12 (B12) inadequacy and high folate and low B12 status, on
      pregnancy outcome are available. However there are no mandatory recommendations
      for B12. There are many forms of B12 viz. Cyanocobalamin (Cbl), Methylcobalamin
      (MeCbl), Adenosylcobalamin (AdCbl), and Hydroxycobalamin (HCbl) though there is
      limited consensus on which form has better efficacy. In the present study we have
      determined effect of various forms of B12 in the presence of two FA
      concentrations namely normal physiological (20ng/mL; NPFA) and supra
      physiological (2000ng/mL; SPFA) concentration to mimic real time situation where
      FA is in excess due to supplementation. We assessed trophoblastic proliferation,
      viability, TNFalpha and EGFr mRNA expression, homocysteine, beta-hCG and MDA
      levels. Trophoblastic viability was significantly suppressed at SPFA
      concentration and was restored by B12 treatment with Cbl, AdCbl and combination
      of MeCbl+AdCbl. The mRNA expressions of TNFalpha were up-regulated, while EGFr
      were down-regulated at SPFA concentrations, as validated by RT-PCR. Treatment
      with MeCbl+AdCbl significantly decreased homocysteine and MDA levels at SPFA
      concentrations. High levels of FA alone had a detrimental effect on placental
      health and functions as reflected by decreased viability, EGFr expression and
      increased TNFalpha expression, homocysteine and MDA levels. Combination of B12
      active forms i.e. MeCbl+AdCbl was found to be most effective in neutralising
      excess folate effect in-vitro.

PMID- 27693965
TI  - Dissolution Dynamic Nuclear Polarization capability study with fluid path.
AB  - Signal enhancement by hyperpolarization is a way of overcoming the low
      sensitivity in magnetic resonance; MRI in particular. One of the most well-known
      methods, dissolution Dynamic Nuclear Polarization, has been used clinically in
      cancer patients. One way of ensuring a low bioburden of the hyperpolarized
      product is by use of a closed fluid path that constitutes a barrier to
      contamination. The fluid path can be filled with the pharmaceuticals, i.e.
      imaging agent and solvents, in a clean room, and then stored or immediately used
      at the polarizer. In this study, we present a method of filling the fluid path
      that allows it to be reused. The filling method has been investigated in terms of
      reproducibility at two extrema, high dose for patient use and low dose for rodent
      studies, using [1-13C]pyruvate as example. We demonstrate that the filling method
      allows high reproducibility of six quality control parameters with standard
      deviations 3-10 times smaller than the acceptance criteria intervals in clinical
      studies.

PMID- 27693964
TI  - Role of oral microbiome on oral cancers, a review.
AB  - The oral cavity is inhibited by many of the bacterial species. Some of them have
      a key role in the development of oral disease. Interrelationships between oral
      microbiome and systemic conditions such as head-and-neck cancer have become
      increasingly appreciated in recent years. Emerging evidence also suggests a link
      between periodontal disease and oral cancer, and the explanation being that
      chronic inflammation could be a major factor in both diseases. Squamous cell
      carcinoma is that the most frequently occurring malignancy of the oral cavity and
      adjacent sites, representing over 90% of all cancers. The incidence of oral
      cancer is increasing, significantly among young people and women. Worldwide there
      are 350,000-400,000 new cases diagnosed every year. Bacteria, viruses, and fungi
      are strongly implicated as etiological factors in certain cancers. In this review
      we will discuss the association between the development of oral cancer in
      potentially malignant oral lesions with chronic periodontitis, chronic
      Porphyromonas gingivalis, Fusobacterium nucleatum, candida, other microbes and
      described mechanisms which may be involved in these carcinoma.

PMID- 27693966
TI  - Scapular dyskinesis: Patterns, functional disability and associated factors in
      people with shoulder disorders.
AB  - BACKGROUND: Patterns of scapular dyskinesis have unique scapular kinematics and
      associated muscular activation. The characteristics of unique dyskinesis patterns
      may be associated with functional disability. OBJECTIVES: To investigate whether
      the shoulder function level and primary dysfunction items were different in
      unique dyskinesis pattern. The factors associated with shoulder dysfunction in
      different dyskinesis patterns were identified. DESIGN: Cross-sectional study.
      METHODS: Fifty-one participants with unilateral shoulder pain were classified as
      having a single dyskinesis pattern (inferior angle prominence, pattern I; medial
      border prominence, pattern II) or a mixed dyskinesis pattern (patterns I + II).
      Clinical measurements with the Flexilevel Scale of Shoulder Function (FLEX-SF),
      shoulder range of motion and pectoralis minor index were recorded. These clinical
      measurements, 3-D scapular kinematics (electromagnetic-based motion analysis),
      and associated muscular activation (electromyography on the upper/middle/lower
      trapezius and serratus anterior muscles) during arm elevation were analyzed for
      associations with functional disability. RESULTS: We found FLEX-SF scores and
      primary dysfunction items were similar among the patterns of dyskinesis. In
      inferior angle prominence, increased shoulder function was associated with
      decreased upper trapezius activity (R2 = 0.155, p = 0.035), which accounted for
      approximately 16% of the variance of FLEX-SF scores. In medial border prominence,
      increased shoulder function was associated with increased lower trapezius
      activity (R2 = 0.131, p = 0.017), which accounted for approximately 13% of the
      variance of FLEX-SF scores. CONCLUSION: Upper and lower trapezius activities are
      important to consider in the evaluation of patients with pattern I and II,
      respectively. No other factors were related to shoulder dysfunction due to
      insufficient challenge of arm elevation tasks.

PMID- 27693967
TI  - RNA-seq reveals differential gene expression in the brains of juvenile resident
      and migratory smolt rainbow trout (Oncorhynchus mykiss).
AB  - Many migratory traits are heritable, but there is a paucity of evidence
      identifying the molecular mechanisms underlying differentiation in alternative
      migratory tactics, or in linking variation in gene expression to migratory
      behaviors. To that end, we examined differential gene expression in the brain
      transcriptome between young steelhead trout that had undergone the smoltification
      process, and resident rainbow trout (Oncorhynchus mykiss) from Sashin Creek,
      Alaska. Samples were sequenced from two time points: immediately before (at
      20months of age) and during (2years of age) the presumed peak of smoltification.
      Smolt and resident individuals came from two genetic crosses, one where both
      parents were migratory, and another where both parents were residents. A total of
      533 (1.9%) genes were differentially expressed between crosses, or between smolt
      and resident samples. These genes include some candidate migratory genes (such as
      POMC), as well as genes with no previous known involvement in the migratory
      process. Progeny from resident parents showed more upregulated genes than progeny
      from migrant parents at both time points. Pathway analysis showed enrichment in
      227 biological pathways between cross type, and 171 biological pathways were
      enriched between residents and smolts. Enriched pathways had connections to many
      biofunctions, and most were only enriched in one contrast. However, pathways
      connected to phototransduction were enriched between both cross type and
      migratory tactics in 11 out of 12 contrasts, suggesting there are fundamental
      differences in how smolts and residents process light in the brain. The genes and
      pathways described herein constitute an a priori candidate list for future
      studies of migration in other populations of O. mykiss, and other migratory
      species.

PMID- 27693968
TI  - Effects of water chemistry on decolorization in three photochemical processes:
      Pro and cons of the UV/AA process.
AB  - The poor selectivity of hydroxyl radicals is a major restriction in the practical
      application of the UV/H2O2 process for dyeing wastewater treatment. As an
      alternative, the target-selective UV/acetylacetone (AA) process was found highly
      efficient for dye decolorization. For the proper selection and application of the
      two photochemical processes, the effects of water matrices, including common
      inorganic anions (Cl-, SO42-, NO3-, HCO3-), natural organic matter, metal cations
      (Mg2+, Mn2+, Cu2+, Fe3+, Cr3+), and temperature, on the photo-degradation of an
      azo dye, Acid Orange 7 (AO7), were systematically investigated. The experimental
      results demonstrate that the UV/AA process was more sensitive to inner filter
      effect. NO3-, Cu2+, and Fe3+ were all detrimental to the UV/AA process, whereas
      at certain concentrations they were beneficial to the UV/H2O2 process. However,
      even with severe inhibitory effects, the decolorization efficiency of the UV/AA
      process was still several times higher than that of the UV/H2O2 process. The
      results are helpful for us to better understand the mechanisms behind the UV/AA
      process and may shed light on the application of UV-based advanced oxidation
      processes for wastewater treatment.

PMID- 27693970
TI  - Effects of current generation and electrolyte pH on reverse salt flux across thin
      film composite membrane in osmotic microbial fuel cells.
AB  - Osmotic microbial fuel cells (OsMFCs) take advantages of synergy between forward
      osmosis (FO) and microbial fuel cells (MFCs) to accomplish wastewater treatment,
      current generation, and high-quality water extraction. As an FO based technology,
      OsMFCs also encounter reverse salt flux (RSF) that is the backward transport of
      salt ions across the FO membrane into the treated wastewater. This RSF can reduce
      water flux, contaminate the treated wastewater, and increase the operational
      expense, and thus must be properly addressed before any possible applications. In
      this study, we aimed to understand the effects of current generation and
      electrolyte pH on RSF in an OsMFC. It was found that electricity generation could
      greatly inhibit RSF, which decreased from 16.3 +/- 2.8 to 3.9 +/- 0.7 gMH when
      the total Coulomb production increased from 0 to 311 C. The OsMFC exhibited 45.9
      +/- 28.4% lower RSF at the catholyte pH of 3 than that at pH 11 when 40 Omega
      external resistance was connected. The amount of sodium ions transported across
      the FO membrane was 18.3-40.7% more than that of chloride ions. Ion transport was
      accomplished via diffusion and electrically-driven migration, and the theoretical
      analysis showed that the inhibited electrically-driven migration should be
      responsible for the reduced RSF. These findings are potentially important to
      control and reduce RSF in OsMFCs or other osmotic-driven processes.

PMID- 27693969
TI  - An activated carbon fiber cathode for the degradation of glyphosate in aqueous
      solutions by the Electro-Fenton mode: Optimal operational conditions and the
      deposition of iron on cathode on electrode reusability.
AB  - An activated carbon fiber (ACF) cathode was fabricated and used to treat
      glyphosate containing wastewater by the Electro-Fenton (EF) process. The results
      showed that glyphosate was rapidly and efficiently degraded and the BOD5/COD
      ratio was increased to >0.3 implying the feasibility of subsequent treatment of
      the treated wastewater by biological methods. The results of ion chromatography
      and HPLC measurements indicated that glyphosate was completely decomposed.
      Effective OH generation and rapid recycling/recovery of the Fe2+ ions at the
      cathode were responsible primarily for the high performance of the ACF-EF
      process. Factors such as inlet oxygen gas flow rate, Fe2+ dosage, initial
      glyphosate concentration, applied current intensity, and solution pH that may
      affect the efficiency of the ACF-EF process were further studied and the optimum
      operation condition was established. Results of SEM/EDX, BET and XPS analysis
      showed the deposition of highly dispersed fine Fe2O3 particles on the ACF surface
      during the EF reaction. The possibility of using the Fe2O3-ACF as iron source in
      the EF process was assessed. Results showed that the Fe2O3-ACF electrode was
      effective in degrading glyphosate in the EF process. The deposition of Fe2O3
      particles on the ACF electrode had no adverse effect on the reusability of the
      ACF cathode.

PMID- 27693971
TI  - Differential decomposition of bacterial and viral fecal indicators in common
      human pollution types.
AB  - Understanding the decomposition of microorganisms associated with different human
      fecal pollution types is necessary for proper implementation of many water
      quality management practices, as well as predicting associated public health
      risks. Here, the decomposition of select cultivated and molecular indicators of
      fecal pollution originating from fresh human feces, septage, and primary effluent
      sewage in a subtropical marine environment was assessed over a six day period
      with an emphasis on the influence of ambient sunlight and indigenous microbiota.
      Ambient water mixed with each fecal pollution type was placed in dialysis bags
      and incubated in situ in a submersible aquatic mesocosm. Genetic and cultivated
      fecal indicators including fecal indicator bacteria (enterococci, E. coli, and
      Bacteroidales), coliphage (somatic and F+), Bacteroides fragilis phage (GB-124),
      and human-associated genetic indicators (HF183/BacR287 and HumM2) were measured
      in each sample. Simple linear regression assessing treatment trends in each
      pollution type over time showed significant decay (p <= 0.05) in most treatments
      for feces and sewage (27/28 and 32/40, respectively), compared to septage (6/26).
      A two-way analysis of variance of log10 reduction values for sewage and feces
      experiments indicated that treatments differentially impact survival of
      cultivated bacteria, cultivated phage, and genetic indicators. Findings suggest
      that sunlight is critical for phage decay, and indigenous microbiota play a
      lesser role. For bacterial cultivated and genetic indicators, the influence of
      indigenous microbiota varied by pollution type. This study offers new insights on
      the decomposition of common human fecal pollution types in a subtropical marine
      environment with important implications for water quality management
      applications.

PMID- 27693972
TI  - The environmental impact of sewage and wastewater outfalls in Antarctica: An
      example from Davis station, East Antarctica.
AB  - We present a comprehensive scientific assessment of the environmental impacts of
      an Antarctic wastewater ocean outfall, at Davis station in East Antarctica. We
      assessed the effectiveness of current wastewater treatment and disposal
      requirements under the Protocol on Environmental Protection to the Antarctic
      Treaty. Macerated wastewater has been discharged from an outfall at Davis since
      the failure of the secondary treatment plant in 2005. Water, sediment and
      wildlife were tested for presence of human enteric bacteria and antibiotic
      resistance mechanisms. Epibiotic and sediment macrofaunal communities were tested
      for differences between sites near the outfall and controls. Local fish were
      examined for evidence of histopathological abnormalities. Sediments, fish and
      gastropods were tested for uptake of sewage as measured by stable isotopes of N
      and C. Escherichia coli carrying antibiotic resistance determinants were found in
      water, sediments and wildlife (the filter feeding bivalve Laternula eliptica).
      Fish (Trematomus bernacchii) within close proximity to the outfall had
      significantly more severe and greater occurrences of histopathological
      abnormalities than at controls, consistent with exposure to sewage. There was
      significant enrichment of 15N in T. bernacchii and the predatory gastropod
      Neobuccinum eatoni around the outfall, providing evidence of uptake of sewage.
      There were significant differences between epibiotic and sediment macrofaunal
      communities at control and outfall sites (<1.5 km), when sites were separated
      into groups of similar habitat types. Benthic community composition was also
      strongly related to habitat and environmental drivers such as sea ice. The
      combined evidence indicated that the discharge of wastewater from the Davis
      outfall is causing environmental impacts. These findings suggest that conditions
      in Antarctic coastal locations, such as Davis, are unlikely to be conducive to
      initial dilution and rapid dispersal of wastewater as required under the Protocol
      on Environmental Protection to the Antarctic Treaty. Current minimum requirements
      for wastewater treatment and disposal in Antarctica are insufficient to
      ameliorate these risks and are likely to lead to accumulation of contaminants and
      introduction of non-native microbes and associated genetic elements. This new
      understanding suggests that modernised approaches to the treatment and disposal
      of wastewater are required in Antarctica. The most effective solution is advanced
      levels of wastewater treatment, which are now possible, feasible and a high
      priority for installation. As a direct outcome of the study, a new advanced
      treatment system is being installed at Davis, effectively avoiding environmental
      risks.

PMID- 27693973
TI  - Financing the HIV response in sub-Saharan Africa from domestic sources: Moving
      beyond a normative approach.
AB  - Despite optimism about the end of AIDS, the HIV response requires sustained
      financing into the future. Given flat-lining international aid, countries'
      willingness and ability to shoulder this responsibility will be central to access
      to HIV care. This paper examines the potential to expand public HIV financing,
      and the extent to which governments have been utilising these options. We develop
      and compare a normative and empirical approach. First, with data from the 14 most
      HIV-affected countries in sub-Saharan Africa, we estimate the potential increase
      in public HIV financing from economic growth, increased general revenue
      generation, greater health and HIV prioritisation, as well as from more
      unconventional and innovative sources, including borrowing, health-earmarked
      resources, efficiency gains, and complementary non-HIV investments. We then adopt
      a novel empirical approach to explore which options are most likely to translate
      into tangible public financing, based on cross-sectional econometric analyses of
      92 low and middle-income country governments' most recent HIV expenditure between
      2008 and 2012. If all fiscal sources were simultaneously leveraged in the next
      five years, public HIV spending in these 14 countries could increase from US$3.04
      to US$10.84 billion per year. This could cover resource requirements in South
      Africa, Botswana, Namibia, Kenya, Nigeria, Ethiopia, and Swaziland, but not even
      half the requirements in the remaining countries. Our empirical results suggest
      that, in reality, even less fiscal space could be created (a reduction by over
      half) and only from more conventional sources. International financing may also
      crowd in public financing. Most HIV-affected lower-income countries in sub
      Saharan Africa will not be able to generate sufficient public resources for HIV
      in the medium-term, even if they take very bold measures. Considerable
      international financing will be required for years to come. HIV funders will need
      to engage with broader health and development financing to improve government
      revenue-raising and efficiencies.

PMID- 27693974
TI  - Promoting physical activity interventions in communities with poor health and
      socio-economic profiles: A process evaluation of the implementation of a new
      walking group scheme.
AB  - Walking groups have known health benefits but may not operate in communities with
      the greatest health needs, leading to the potential for increasing health
      inequity. This study examined the process of implementing a new volunteer led
      walking group scheme in a deprived community in England with poor physical
      activity, health and socio-economic indicators. Documentary evidence and semi
      structured interviews with stakeholders and volunteer walk leaders undertaken at
      the beginning and end of the funding period were analysed thematically. It was
      found that utilising community-based assets, forming collaborative partnerships
      with health and non-health organisations and ongoing sustainability issues were
      all factors that affected the scheme's effective implementation. Passive
      recruitment methods and mass publicity did not attract participants who were
      representative of their community. The findings firstly suggest the necessity of
      identifying and mobilising community based assets at the 'grass roots' in
      deprived communities during the preparatory stage to access those in greatest
      need and to plan and build capacity. Secondly, the findings highlight the key
      role that health professionals have in referring those in poorest health and the
      inactive into walking interventions. In the new era of fiscally constrained
      public health embedded within local authorities these findings are pertinent in
      supporting the utilisation of local assets to address entrenched physical
      inactivity and inequity within deprived communities.

PMID- 27693975
TI  - Valproate for agitation in critically ill patients: A retrospective study.
AB  - PURPOSE: The purpose was to describe the use of valproate therapy for agitation
      in critically ill patients, examine its safety, and describe its relationship
      with agitation and delirium. MATERIALS AND METHODS: This retrospective cohort
      study evaluated critically ill adults treated with valproate for agitation from
      December 2012 through February 2015. Information on valproate prescribing
      practices and safety was collected. Incidence of agitation, delirium, and
      concomitant psychoactive medication use was compared between valproate day 1 and
      valproate day 3. Concomitant psychoactive medication use was analyzed using mixed
      models. RESULTS: Fifty-three patients were evaluated. The median day of valproate
      therapy initiation was ICU day 7, and it was continued for a median of 7 days.
      The median maintenance dose was 1500 mg/d (23 mg/kg/d). The incidence of
      agitation (96% vs 61%, P < .0001) and delirium (68% vs 49%, P = .012)
      significantly decreased by valproate day 3. Treatment with opioids (77% vs 65%, P
      = .02) and dexmedetomidine (47% vs 24%, P = .004) also decreased. In mixed models
      analyses, valproate therapy was associated with reduced fentanyl equivalents (
      185 MUg/d, P = .0003) and lorazepam equivalents (-2.1 mg/d, P = .0004).
      Hyperammonemia (19%) and thrombocytopenia (13%) were the most commonly observed
      adverse effects. CONCLUSIONS: Valproate therapy was associated with a reduction
      in agitation, delirium, and concomitant psychoactive medication use within 48
      hours of initiation.

PMID- 27693976
TI  - Cumulative arsenic exposure is associated with fungal infections: Two cohort
      studies based on southwestern and northeastern basins in Taiwan.
AB  - Long-term arsenic exposure results in atherosclerosis and cancers, along with
      aberrant immune responses. Animal-based and epidemiological studies indicate that
      arsenic exposure increases susceptibility to viral and bacterial infections. This
      study aimed to assess whether arsenic exposure is associated with the development
      of fungal infection, which is substantially attributed to as a cause of aberrant
      immunity. Based on two well-established cohorts from two basins in southwestern
      (SW; high arsenic area) and northeastern (NE; low arsenic area) Taiwan (n=297 and
      2738, respectively), the arsenic exposure in well water was estimated using HPLC
      ICP-MS. Fungal infections were defined via clinical and mycological assessments
      (PCR of fungal 18S rRNA) of nail samples. Individuals in SW cohort with
      cumulative arsenic exposure >10,000MUg/L*years had a higher risk of developing
      fungal infections (OR=1.57, 95% CI=1.08-1.92) after adjusting for diabetes and
      occupation. In NE cohort, female sex, alcohol consumption, and chronic kidney
      diseases were associated with toenail infections. In contrast, fingernail
      infections (OR=1.33, 95% CI=1.05-1.68) were highly associated with arsenic
      exposure in a dose-dependent manner. We are the first to report palmar and
      plantar hyperkeratosis upon low arsenic exposure in 3.9% and 6.7% individuals,
      respectively. This is the first large-scale study showing arsenic exposure is
      associated with fungal infections in a dose-dependent manner.

PMID- 27693977
TI  - Differential fMRI BOLD responses in amygdala in intermittent explosive disorder
      as a function of past Alcohol Use Disorder.
AB  - BACKGROUND: Individuals with intermittent explosive disorder (IED) were
      previously found to exhibit amygdala (AMYG) hyperactivation to anger faces during
      functional magnetic resonance imaging (fMRI). However, acute alcohol consumption,
      and/or life history of alcoholism, may blunt amygdala responses to negative
      emotional stimuli. Thus, we examined the influence of a past history of DSM-5
      Alcohol Use Disorder (AUD) on the fMRI BOLD AMYG response to anger faces in IED.
      METHOD: Forty-two IED participants, 18 with a past history of AUD (IED+AUD) and
      24 without Past AUD (IED), and 32 healthy control (HC) participants, underwent
      fMRI scanning while viewing blocks of angry, fearful, and happy faces. RESULTS:
      Compared to HC and IED+AUD participants, IED subjects exhibited greater AMYG
      responses to angry, but not to fear or happy, faces in the left AMYG. There were
      no group differences in responses to anger, fear, or happy, faces in the OFC.
      CONCLUSION: These findings suggest the possibility of a longstanding effect of
      AUD on AMYG response in IED to anger-related stimuli and highlight the
      possibility that history of AUD should be considered as an important factor in
      the interpretation of fMRI studies involving the AMYG response to negative
      emotional stimuli.

PMID- 27693979
TI  - Polymorphisms in PDLIM5 gene are associated with alcohol dependence, type 2
      diabetes, and hypertension.
AB  - The PDZ and LIM domain 5 (PDLIM5) gene may play a role in alcohol dependence
      (AD), bipolar disorder, and major depressive disorder; however, no study has
      identified shared genetic variants within PDLIM5 gene among AD, type 2 diabetes
      (T2D), and hypertension. This study investigated the association of 72 single
      nucleotide polymorphism (SNPs) with AD (1066 AD cases and 1278 controls) in the
      Study of Addiction - Genetics and Environment (SAGE) sample and 47 SNPs with T2D
      (878 cases and 2686 non-diabetic) and hypertension (825 cases and 2739 non
      hypertensive) in the Marshfield sample. Multiple logistic regression models in
      PLINK software were used to examine the associations of genetic variants with AD,
      T2D, and hypertension and SNP x alcohol consumption interactions for T2D and
      hypertension. Twenty-five SNPs were associated with AD in the SAGE sample (p <
      0.05); rs1048627 showed the strongest association with AD (p = 5.53 * 10-4). Of
      the 25 SNPs, 5 SNPs showed associations with both AD in the SAGE sample and T2D
      in the Marshfield sample (top SNP rs11097432 with p = 0.00107 for T2D and p =
      0.0483 for AD) while 6 SNPs showed associations with both AD in the SAGE sample
      and hypertension in the Marshfield sample (top SNP rs12500426 with p = 0.0119 for
      hypertension and p = 1.51 * 10-3 for AD). SNP (rs6532496) showed significant
      interaction with alcohol consumption for hypertension. Our results showed that
      several genetic variants in PDLIM5 gene influence AD, T2D and hypertension. These
      findings offer the potential for new insights into the pathogenesis of AD, T2D,
      and hypertension.

PMID- 27693980
TI  - Prospective prediction of first lifetime suicide attempts in a multi-site study
      of substance users.
AB  - Although considerable empirical work has been devoted to identifying risk factors
      for suicide attempts, most longitudinal research has studied recurrent attempts
      rather than first lifetime attempts. The present study sought to examine
      prospective predictors of first lifetime suicide attempts among adults receiving
      treatment for substance use. Data were drawn from the National Treatment
      Improvement Evaluation Study, a study of addiction treatment programs. Data were
      collected at treatment intake, treatment exit, and one year post-treatment.
      Patients (n = 3518) with no lifetime history of suicide attempts at treatment
      intake were followed at treatment exit and one year post-treatment, when they
      reported on the occurrence of suicide attempts since the prior assessment.
      Prospective suicidal behavior was assessed using logistic regression in relation
      to sociodemographic variables, health-related work impairment, history of
      psychiatric treatment utilization, history of suicidal ideation, history of
      depressive symptoms, substance use, and childhood abuse, assessed at intake.
      Health-related work impairment, history of suicidal ideation, and childhood
      physical abuse significantly predicted first lifetime attempts in a multivariate
      analysis. Suicidal ideation, health-related functional impairments, and childhood
      physical abuse may be particularly important in assessing risk for first lifetime
      suicide attempts. Findings suggest that future clinical work and research would
      benefit from considering these factors when identifying individuals at heightened
      risk of making a first suicide attempt.

PMID- 27693981
TI  - Anxious distress predicts subsequent treatment outcome and side effects in
      depressed patients starting antidepressant treatment.
AB  - Evidence has shown that the DSM-5 anxious distress specifier captures a
      clinically valid construct that predicts a worse clinical course. Although of
      importance for treatment planning and monitoring, however, the specifier's
      ability to predict treatment outcome is unknown. This is the first study to
      examine the ability of the DSM-5 anxious distress specifier to predict treatment
      response and side effects in depressed patients who recently initiated
      antidepressant treatment. Patients were from the Netherlands Study of Depression
      and Anxiety, an ongoing longitudinal cohort study. Baseline, 1-year and 2-year
      follow-up data were used from 149 patients (18-65 years) with current Major
      Depressive Disorder (MDD) who recently started adequately dosed antidepressant
      medication. Five self-report items were used to construct the DSM-5 anxious
      distress specifier. Treatment outcomes were depression severity after 1 year and
      2 years, remission of MDD after 2 years and antidepressant side effects during
      treatment. For comparison, analyses were repeated for comorbid DSM-IV-based
      anxiety disorders as a predictor. In depressed patients who received
      antidepressant treatment, the anxious distress specifier (prevalence = 59.1%)
      significantly predicted higher severity (1 year: B = 1.94, P = 0.001; 2 years: B
      = 1.63, P = 0.001), lower remission rates (OR = 0.44, P = 0.0496) and greater
      frequency of side effects (>=4 vs. 0: OR = 2.74, P = 0.061). In contrast, the
      presence of comorbid anxiety disorders did not predict these treatment outcomes.
      The anxious distress specifier significantly predicts poorer treatment outcomes
      as shown by higher depression severity, lower remission rates, and greater
      frequency of antidepressant side effects in patients with MDD on adequate
      antidepressant treatment. Therefore, this simple 5-item specifier is of potential
      great clinical usefulness for treatment planning and monitoring in depressed
      patients.

PMID- 27693982
TI  - Prenatal betamethasone exposure and psychopathology risk in extremely low birth
      weight survivors in the third and fourth decades of life.
AB  - BACKGROUND: Mortality rates among extremely low birthweight (ELBW) infants have
      declined since the advent of antenatal glucocorticoid use. However, the long term
      neuropsychiatric effects of exposure are not well understood. We utilized the
      world's oldest longitudinally followed cohort of ELBW survivors to compare
      psychopathology over two decades in adulthood in those exposed to prenatal
      betamethasone and those who were not. METHODS: ELBW survivors (n=179) and matched
      normal birth weight (NBW) controls (n=145) completed the Young Adult Self-Report
      questionnaire at 22-26 and 29-36 years, and the Beck Depression and Anxiety
      Inventories at 29-36 years. Symptom levels and rates of clinically significant
      psychiatric problems were compared in ELBW survivors whose mothers were
      administered steroids during pregnancy (ELBW-S n=63), ELBW participants who were
      not (ELBW-NS, n=79), and NBW controls. RESULTS: At 22-26, ELBW-S had higher
      levels of anxiety, depressive, and avoidant personality symptoms, and a 3 to 5
      fold increase in the odds of clinically significant levels of these problems
      compared to NBW controls, whereas ELBW-NS did not. These associations were
      maintained at 29-36, when ELBW-S participants exhibited a 3 to 10-fold increase
      in the odds of clinically significant anxiety and avoidant personality problems
      compared to NBW controls. At both time points, the odds of clinically significant
      anxiety problems were more than 3 times higher among ELBW-S than in ELBW-NS.
      CONCLUSION: ELBW adults exposed to prenatal betamethasone manifest higher levels
      of anxiety and depression than those who were not, and may represent a group of
      preterm survivors at particularly high psychiatric risk.

PMID- 27693978
TI  - Acupuncture treatment modulates the corticostriatal reward circuitry in major
      depressive disorder.
AB  - Major depressive disorder (MDD) is a common disorder with a high prevalence and
      significant social and economic impacts. Nevertheless, the treatment of MDD is
      far from satisfactory. Acupuncture treatment has emerged as a promising method
      for treating MDD. However, the neural mechanism by which acupuncture reduces
      depressive symptoms is not fully understood. Studies have shown that the
      corticostriatal reward circuitry is associated with the pathophysiology of MDD;
      thus, we investigated the corticostriatal resting-state functional connectivity
      (rsFC) before and after real and sham acupuncture treatments combined with the
      antidepressant fluoxetine. Forty-six female major depressive patients were
      assigned to either verum acupuncture plus fluoxetine (n = 22) or sham acupuncture
      plus fluoxetine (n = 24) treatment for 8 weeks, and resting state functional
      magnetic resonance imaging (fMRI) data were collected before the first and after
      the last treatment sessions. The results showed that compared with sham
      acupuncture, the verum acupuncture group showed: (1) significantly increased rsFC
      between inferior ventral striatum and medial prefrontal cortex, ventral rostral
      putamen and amygdala/parahippocampus, as well as dorsal caudate and middle
      temporal gyrus; (2) significantly decreased rsFC between right ventral rostral
      putamen and right dorsolateral prefrontal cortex, and right dorsal caudate and
      bilateral cerebellar tonsil. The increased rsFC between the inferior ventral
      striatum and medial prefrontal cortex, ventral rostral putamen and
      amygdala/parahippocampus were significantly positively associated with decreased
      clinical scores (Montgomery-Asberg Depression Rating Scale and Self-Rating
      Depression Scale scores) at the end of the eight-week treatment. Our findings
      suggest that acupuncture may achieve treatment effects by modulating the
      corticostriatal reward/motivation circuitry in MDD patients.

PMID- 27693983
TI  - Parenting and childhood atopic dermatitis: A cross-sectional study of
      relationships between parenting behaviour, skin care management, and disease
      severity in young children.
AB  - BACKGROUND: The development of child behaviour and parenting difficulties is
      understood to undermine treatment outcomes for children with atopic dermatitis.
      Past research has reported on correlates of child behaviour difficulties.
      However, few research studies have sought to examine parenting confidence and
      practices in this clinical group. OBJECTIVES: To examine relationships between
      child, parent, and family variables, parent-reported and directly-observed child
      and parent behaviour, parents' self-efficacy with managing difficult child
      behaviour, self-reported parenting strategies, and disease severity. DESIGN:
      Cross-sectional study design. PARTICIPANTS: Parent-child dyads (N=64) were
      recruited from the dermatology clinic of a paediatric tertiary referral hospital
      in Brisbane, Australia. Children had a diagnosis of atopic dermatitis of
      >=3months and no other chronic health conditions except asthma, allergic
      rhinitis, or allergy. METHODS: Parents completed self-report measures assessing
      child behaviour; parent depression, anxiety, and stress; parenting conflict and
      relationship satisfaction; self-efficacy with managing difficult child behaviour,
      and use of ineffective parenting strategies; and self-efficacy for managing
      atopic dermatitis, and performance of atopic dermatitis management tasks. The
      Scoring Atopic Dermatitis index was used to assess disease severity. Routine at
      home treatment sessions were coded for parent and child behaviour. RESULTS:
      Pearson's and Spearman's correlations identified relationships (p<0.05) between
      self-efficacy with managing difficult child behaviour and child behaviour
      problems, parent depression and stress, parenting conflict and relationship
      satisfaction, and household income. There were also relationships between each of
      these variables and use of ineffective parenting strategies. Greater use of
      ineffective parenting strategies was associated with more severe atopic
      dermatitis. Using multiple linear regressions, child behaviour and household
      income explained unique variance in self-efficacy for managing difficult child
      behaviour; household income alone explained unique variance in use of ineffective
      parenting strategies. Self-efficacy for managing difficult child behaviour and
      self-efficacy for managing atopic dermatitis were positively correlated
      (rho=0.48, p<0.001), and more successful self-reported performance of atopic
      dermatitis management tasks correlated with less permissive (r=0.35, p=0.005) and
      less authoritarian (r=0.41, p=0.001) parenting. Directly observed aversive child
      behaviour was associated with more severe atopic dermatitis, parent stress, and
      parent-reported child behaviour problems. CONCLUSION: This study revealed
      relationships between parents' self-efficacy and parenting practices across the
      domains of child behaviour management and atopic dermatitis management. Parents
      of children with more severe atopic dermatitis may have difficulty responding to
      child behaviour difficulties appropriately, potentially impacting on illness
      management. Incorporating parent and parenting support within treatment plans may
      improve not only child and family wellbeing, but also treatment outcomes.

PMID- 27693984
TI  - Implementation of an established algorithm and modifications for the
      identification of epilepsy patients in the veterans health administration.
AB  - Identification of epilepsy patients from administrative data in large managed
      healthcare organizations is a challenging task. The objectives of this report are
      to describe the implementation of an established algorithm and different
      modifications for the estimation of epilepsy prevalence in the Veterans Health
      Administration (VHA). For the prevalence estimation during a given time period
      patients prescribed anti-epileptic drugs and having seizure diagnoses on clinical
      encounters were identified. In contrast to the established algorithm, which
      required inclusion of diagnoses data from the time period of interest only,
      variants were tested by considering diagnoses data beyond prevalence period for
      improving sensitivity. One variant excluded data from diagnostic EEG and LTM
      clinics to improve specificity. Another modification also required documentation
      of seizures on the problem list (electronic list of patients' established
      diagnoses). Of the variants tested, the one excluding information from diagnostic
      clinics and extending time beyond base period of interest for clinical encounters
      was determined to be superior. It can be inferred that the number of patients
      receiving care for epilepsy in the VHA ranges between 74,000 and 87,000. In the
      wake of the recent implementation of ICD-10 codes in the VHA, minor tweaks are
      needed for future prevalence estimation due to significant efforts presented.
      This review is not only beneficial for researchers interested in VHA related data
      but can also be helpful for managed healthcare organizations involved in epilepsy
      care aiming at accurate identification of patients from large administrative
      databases.

PMID- 27693985
TI  - Accuracy of MEG in localizing irritative zone and seizure onset zone:
      Quantitative comparison between MEG and intracranial EEG.
AB  - BACKGROUND: We conducted the study to examine accuracy of the
      magnetoencephalography (MEG) spike source localization in presurgical evaluation
      of patients with medically refractory focal epilepsy. METHODS: Ten consecutive
      patients with refractory focal epilepsy who were candidates for two-stage surgery
      with long-term intracranial electroencephalography (ICEEG) monitoring were
      enrolled. Interictal MEG recordings with simultaneous scalp EEG were obtained
      within 7days before the ICEEG electrode implantation. The location of each MEG
      spike source was quantitatively compared with ICEEG spike foci (focal area of
      interictal spikes) and ICEEG ictal foci (earliest cortical origin of seizures).
      Gyral-width concordance and sublobar concordance were also determined for all MEG
      spike sources. Gyral-width concordance was defined by distance of 15mm or less
      between MEG spike sources and ICEEG spike foci or ICEEG ictal foci. RESULTS:
      Visual analyses of the MEG traces of all 10 patients revealed 292 spikes (29.2+/
      24.0 per patient). Spike yield of the MEG was similar to the simultaneously
      recorded scalp EEG. MEG spike sources were closely located with ICEEG spike foci
      (distance: 9.3+/-10.8mm). Clustered MEG spike sources were even closer to ICEEG
      spike foci (distance: 7.3+/-6.4mm). MEG spike sources, even clustered ones, were
      less concordant with ICEEG ictal foci and had significant longer distance from
      ICEEG ictal foci (distance: 21.5+/-15.6mm for all sources, 19.7+/-13.7mm for
      clustered sources). Gyral-width concordance rate and sublobar concordance rate
      were also higher with ICEEG interictal spike foci than with ICEEG ictal foci. On
      the other hand, 53.4% of interictal spike foci from ICEEG were not detected by
      interictal MEG recordings. CONCLUSIONS: MEG spike sources, especially clustered
      ones, from interictal recording could localize the irritative zone of ICEEG with
      a high accuracy. However, MEG spike sources have relatively poor correlation with
      seizure onset zone and lower sensitivity in identifying all irritative zones of
      ICEEG. This limitation should be considered in the interpretation of MEG results.

PMID- 27693987
TI  - Metabolic analysis of two contrasting wild barley genotypes grown hydroponically
      reveals adaptive strategies in response to low nitrogen stress.
AB  - Nitrogen (N) is an essential macronutrient for plants. The increasingly severe
      environmental problems caused by N fertilizer application urge alleviation of N
      fertilizer dependence in crop production. In previous studies, we identified the
      Tibetan wild barley accessions with high tolerance to low nitrogen (LN). In this
      study, metabolic analysis was done on two wild genotypes (XZ149, tolerant and
      XZ56, sensitive) to understand the mechanism of LN tolerance, using a hydroponic
      experiment. Leaf and root samples were taken at seven time points within 18 d
      after LN treatment, respectively. XZ149 was much less affected by low N stress
      than XZ56 in plant biomass. A total of 51 differentially accumulated metabolites
      were identified between LN and normal N treated plants. LN stress induced tissue
      specific changes in carbon and nitrogen partitioning, and XZ149 had a pattern of
      energy-saving amino acids accumulation and carbon distribution in favor of root
      growth that contribute to its higher LN tolerance. Moreover, XZ149 is highly
      capable of producing energy and maintaining the redox homeostasis under LN
      stress. The current results revealed the mechanisms underlying the wild barley in
      high LN tolerance and provided the valuable references for developing barley
      cultivars with LN tolerance.

PMID- 27693986
TI  - Magnetoencephalography spike sources interrelate the extensive epileptogenic zone
      of tuberous sclerosis complex.
AB  - OBJECTIVE: We hypothesized that the extensive epileptic network in patients with
      tuberous sclerosis complex (TSC) manifests as clustered and scattered
      distributions of magnetoencephalography spike sources (MEGSS). METHODS: We
      retrospectively analyzed pre-surgical MEG in 15 patients with TSC. We performed
      single moving dipole analysis to localize and classify clustered and scattered
      MEGSS. We compared the number of electrodes within the resected area (RA) and the
      proportions of clustered and scattered MEGSS within RA with the seizure outcome.
      RESULTS: The number of electrodes within RA ranged from 29 to 83 (mean=51). The
      MEGSS were distributed over multiple lobes (3-8; mean=5.9) and bilaterally in 14
      patients. Clusters of MEGSS ranged from 1 to 4 (mean=1.4). The number of MEGSS
      ranged in total from 28 to 139 (mean=70); in the clusters, 10-128 (mean=49); and
      in the scatters, 0-45 (mean=21). Four patients achieved an Engel class I surgical
      outcome, four, a class II outcome; five, a class III outcome; and two, a class IV
      outcome. The proportion of MEGSS ranged in total from 0 to 92% (mean=57%) within
      RA; 0-100% (mean=67%) in the resection hemisphere; 0-100% (mean=63%) in the
      clusters; and 0-81% (mean=28%) in the scatters. Univariate ordinal logistic
      regression analyses showed that the proportion of scattered MEGSS within RA
      (p=0.049) significantly correlated with seizure outcomes. Multivariate analyses
      using three covariates (number of electrodes, proportions of clustered and
      scattered MEGSS within RA) showed that only the proportion of scattered MEGSS
      within RA significantly correlated with seizure outcomes (p=0.016). SIGNIFICANCE:
      MEG data showed a wide distribution of multilobar MEGSS in patients with TSC. The
      seizure outcome was not related to the clustered MEGSS within RA, since the grids
      were essentially planned to cover and resect the clustered MEGSS surrounding
      tubers. The maximal possible resection of scattered MEGSS correlated with
      improved seizure outcome in TSC. Some parts of the epileptogenic zone disrupted
      by multiple tubers did not have a sufficiently large area to produce clustered
      MEGSS. Although the wide distribution of scattered MEGSS is not interpreted as
      epileptogenic, they might be interrelated with clustered MEGSS to project a
      complex epilepsy network and be part of the extensive epileptogenic zones found
      in TSC.

PMID- 27693988
TI  - Gestational and lactational exposure to low-dose bisphenol A increases Th17 cells
      in mice offspring.
AB  - Increasing evidence demonstrates that perinatal exposure to Bisphenol A (BPA) can
      cause immune disorders throughout the life span. However, the biological basis
      for these immune disorders is poorly understood and the effects of exposure to
      BPA on Th17 development are unknown. The present study sought to characterize
      alterations of Th17 cells in childhood and adulthood following gestational and
      lactational exposure to environmentally relevant low-dose of BPA and the
      underlying mechanisms. Pregnant dams were exposed to BPA (10, 100 or 1000nM) via
      drinking water from gestational day (GD) 0 to postnatal day (PND) 21. At PNDs 21
      and 42, offspring mice were anesthetized, blood was obtained for cytokine assay
      and spleens were collected for Th17 cell frequency and RORgammat mRNA expression
      analysis. Perinatal exposure to low-dose BPA resulted in a dose-dependent and
      gender-specific persistent rise in Th17 cells accompanied by an increase of
      RORgammat mRNA expression in the offsprings. The contents of major Th17 cell
      derived cytokines (IL-17 and IL-21) and those essential for Th17 cell
      differentiation (IL-6 and IL-23) were also increased compared to those in
      controls. These changes were more pronounced in female than in male offsprings.
      However, perinatal exposure to low-dose BPA had little effect on serum TGF-beta,
      another key regulator for Th17 cell development. Our results suggest that
      gestational and lactational exposure to a low-dose of BPA can affect Th17 cell
      development via an action on its transcription factor and the regulatory
      cytokines. These findings provide novel insight into sustained immune disorders
      by BPA exposure during development.

PMID- 27693989
TI  - A hip abduction exercise prior to prolonged standing increased movement while
      reducing cocontraction and low back pain perception in those initially reporting
      low back pain.
AB  - Persons who develop low back pain from prolonged standing exhibit increased
      muscle cocontraction, decreased movement and increased spine extension. However,
      it is unclear how these factors relate to pain development. The purpose of this
      study was to use hip abductor fatigue to manipulate muscle activity patterns and
      determine its effects on standing behaviours and pain development. Forty
      participants stood for two hours twice, once following a hip abductor fatigue
      exercise (fatigue), and once without exercise beforehand (control). Trunk and
      gluteal muscle activity were measured to determine cocontraction. Lumbo-pelvic
      angles and force plates were used to assess posture and movement strategies.
      Visual analog scales differentiated pain (PDs) and non-pain developers (NPDs).
      PDs reported less low back pain during the fatigue session, with females having
      earlier reductions of similar scale than males. The fatigue session reduced
      gluteal and trunk cocontraction and increased centre of pressure movement; male
      and female PDs had opposing spine posture compensations. Muscle fatigue prior to
      standing reduced cocontraction, increased movement during standing and reduced
      the low back pain developed by PDs; the timing of pain reductions depended on
      spine postures adopted during standing.

PMID- 27693990
TI  - Mcconnell's patellar taping does not alter knee and hip muscle activation
      differences during proprioceptive exercises: A randomized placebo-controlled
      trial in women with patellofemoral pain syndrome.
AB  - : The purpose of this study was to assess the effect of patellar taping on muscle
      activation of the knee and hip muscles in women with Patellofemoral Pain Syndrome
      during five proprioceptive exercises. Forty sedentary women with syndrome were
      randomly allocated in two groups: Patellar Taping (based in McConnell) and
      Placebo (vertical taping on patella without any stretching of lateral structures
      of the knee). Volunteers performed five proprioceptive exercises randomly: Swing
      apparatus, Mini-trampoline, Bosu balance ball, Anteroposterior sway on a
      rectangular board and Mediolateral sway on a rectangular board. All exercises
      were performed in one-leg stance position with injured knee at flexion of 30
      degrees  during 15s. Muscle activation was measured by surface electromyography
      across Vastus Medialis, Vastus Lateralis and Gluteus medius muscles. Maximal
      voluntary contraction was performed for both hip and knee muscles in order to
      normalize electromyography signal relative to maximum effort during the
      exercises. ANOVA results reported no significant interaction (P>0.05) and no
      significant differences (P>0.05) between groups and intervention effects in all
      exercise conditions. Significant differences (P<0.01) were only reported between
      muscles, where hip presented higher activity than knee muscles. Patellar taping
      is not better than placebo for changes in the muscular activity of both hip and
      knee muscles during proprioceptive exercises. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov NCT02322515.

PMID- 27693991
TI  - Simplifying and expanding analytical capabilities for various classes of doping
      agents by means of direct urine injection high performance liquid chromatography
      high resolution/high accuracy mass spectrometry.
AB  - So far, in sports drug testing compounds of different classes are processed and
      measured using different screening procedures. The constantly increasing number
      of samples in doping analysis, as well as the large number of substances with
      doping related, pharmacological effects require the development of even more
      powerful assays than those already employed in sports drug testing, indispensably
      with reduced sample preparation procedures. The analysis of native urine samples
      after direct injection provides a promising analytical approach, which thereby
      possesses a broad applicability to many different compounds and their
      metabolites, without a time-consuming sample preparation. In this study, a novel
      multi-target approach based on liquid chromatography and high resolution/high
      accuracy mass spectrometry is presented to screen for more than 200 analytes of
      various classes of doping agents far below the required detection limits in
      sports drug testing. Here, classic groups of drugs as diuretics, stimulants,
      beta2-agonists, narcotics and anabolic androgenic steroids as well as various
      newer target compounds like hypoxia-inducible factor (HIF) stabilizers, selective
      androgen receptor modulators (SARMs), selective estrogen receptor modulators
      (SERMs), plasma volume expanders and other doping related compounds, listed in
      the 2016 WADA prohibited list were implemented. As a main achievement, growth
      hormone releasing peptides could be implemented, which chemically belong to the
      group of small peptides (<2kDa) and are commonly determined by laborious and time
      consuming stand-alone assays. The assay was fully validated for qualitative
      purposes considering the parameters specificity, robustness (rRT: <2%), intra-
      (CV: 1.7-18.4 %) and inter-day precision (CV: 2.3-18.3%) at three concentration
      levels, linearity (R2>0.99), limit of detection (0.1-25ng/mL; 3'OH-stanozolol
      glucuronide: 50pg/mL; dextran/HES: 10MUg/mL) and matrix effects.

PMID- 27693993
TI  - The C of CHADS: Historical perspective and clinical applications for
      anticoagulation in patients with non valvular atrial fibrillation and congestive
      heart failure.
AB  - The risk stratification of patients with coexisting non valvular atrial
      fibrillation and congestive heart failure, is often a clinical challenge, as the
      definitions of congestive heart failure in the popular CHADS2 and CHA2DS2VASc
      scoring systems, and amongst major clinical trials on Warfarin and Novel Oral
      Anticoagulants (NOAC) have heterogeneity. Available evidence reveals that any
      heart failure and/or left ventricular systolic dysfunction is associated with
      higher rates of stroke/systemic embolism and bleeding in patients with non
      valvular atrial fibrillation compared to patients without heart failure and
      normal left ventricular function. Most standard dose NOAC regimens have a better
      safety and efficacy profile over warfarin in most heart failure sub-group types
      with a few exceptions including patients with NYHA III/IV on Dabigatran 150mg BID
      from the RE-LY trial, who had higher major bleeding events, and patients with
      asymptomatic left ventricular dysfunction (ejection fraction <=40%) and heart
      failure with reduced ejection fraction on 20mg of Rivaroxaban in the ROCKET-AF
      trial, when compared to patients on Warfarin in the corresponding groups. With
      the gaining popularity and use of NOACs, understanding their safety profile in
      such situations is paramount.

PMID- 27693992
TI  - The redox mechanism for vascular barrier dysfunction associated with metabolic
      disorders: Glutathionylation of Rac1 in endothelial cells.
AB  - BACKGROUND: Oxidative stress is implicated in increased vascular permeability
      associated with metabolic disorders, but the underlying redox mechanism is poorly
      defined. S-glutathionylation, a stable adduct of glutathione with protein
      sulfhydryl, is a reversible oxidative modification of protein and is emerging as
      an important redox signaling paradigm in cardiovascular physiopathology. The
      present study determines the role of protein S-glutathionylation in metabolic
      stress-induced endothelial cell permeability. METHODS AND RESULTS: In endothelial
      cells isolated from patients with type-2 diabetes mellitus, protein S
      glutathionylation level was increased. This change was also observed in aortic
      endothelium in ApoE deficient (ApoE-/-) mice fed on Western diet. Metabolic
      stress-induced protein S-glutathionylation in human aortic endothelial cells
      (HAEC) was positively correlated with elevated endothelial cell permeability, as
      reflected by disassembly of cell-cell adherens junctions and cortical actin
      structures. These impairments were reversed by adenoviral overexpression of a
      specific de-glutathionylation enzyme, glutaredoxin-1 in cultured HAECs.
      Consistently, transgenic overexpression of human Glrx-1 in ApoE-/- mice fed the
      Western diet attenuated endothelial protein S-glutathionylation, actin
      cytoskeletal disorganization, and vascular permeability in the aorta.
      Mechanistically, glutathionylation and inactivation of Rac1, a small RhoGPase,
      were associated with endothelial hyperpermeability caused by metabolic stress.
      Glutathionylation of Rac1 on cysteine 81 and 157 located adjacent to guanine
      nucleotide binding site was required for the metabolic stress to inhibit Rac1
      activity and promote endothelial hyperpermeability. CONCLUSIONS:
      Glutathionylation and inactivation of Rac1 in endothelial cells represent a novel
      redox mechanism of vascular barrier dysfunction associated with metabolic
      disorders.

PMID- 27693994
TI  - Effectiveness of hypolimnetic oxygenation for preventing accumulation of Fe and
      Mn in a drinking water reservoir.
AB  - The accumulation of Fe and Mn in seasonally stratified drinking water reservoirs
      adversely impacts water quality. To control issues with Fe and Mn at the source,
      some drinking water utilities have deployed hypolimnetic oxygenation systems to
      create well-oxygenated conditions in the water column that are favorable for the
      oxidation, and thus removal, of Fe and Mn. However, in addition to being
      controlled by dissolved oxygen (DO), Fe and Mn concentrations are also influenced
      by pH and metal-oxidizing microorganisms. We studied the response of Fe and Mn
      concentrations to hypolimnetic oxygenation in a shallow drinking water reservoir
      in Vinton, Virginia, USA by sequentially activating and deactivating an
      oxygenation system over two summers. We found that maintaining well-oxygenated
      conditions effectively prevented the accumulation of soluble Fe in the
      hypolimnion. However, while the rate of Mn oxidation increased under well
      oxygenated conditions, soluble Mn still accumulated in the slightly acidic to
      neutral (pH 5.6 to 7.5) hypolimnion. In parallel, we conducted laboratory
      incubation experiments, which showed that the presence of Mn-oxidizing
      microorganisms increased the rate of Mn oxidation in comparison with rates under
      oxic, abiotic conditions. Combined, our field and laboratory results demonstrate
      that increasing DO concentrations in the water column is important for
      stimulating the oxidation of Fe and Mn, but that the successful management of Mn
      is also tied to the activity of Mn-oxidizing organisms in the water column and
      favorable (neutral to alkaline) pH.

PMID- 27693995
TI  - Immobilization of Cd in river sediments by sodium alginate modified nanoscale
      zero-valent iron: Impact on enzyme activities and microbial community diversity.
AB  - This paper investigated how sodium alginate (SA)-modified nanoscale zero-valent
      iron (NZVI), play a constructive role in the remediation of cadmium (Cd)
      contaminated river sediments. The changes of the fraction of Cd, enzyme
      activities (urease, catalase, dehydrogenase) and bacterial community structures
      with the treatment by SNZVI were observed. The sequential extraction experiments
      demonstrated that most mobile fractions of Cd were transformed into residues (the
      maximum residual percentage of Cd increases from 15.49% to 57.28% after 30 days
      of incubation at 0.1 wt% SA), with the decrease of bioavailability of Cd.
      Exclusive of dehydrogenase, the activities of the other two enzymes tested were
      enhanced with the increase of incubation time, which indicated that dehydrogenase
      might be inhibited by ferric ions formed from SNZVI whereas no obvious inhibition
      was found for other enzymes. Polymerase chain reaction denaturing gradient gel
      electrophoresis (PCR-DGGE) analyses were used for the detection of microbial
      community changes, and the results showed that SNZVI and NZVI could increase
      bacterial taxa and improve bacterial abundance. All the experimental findings of
      this study provide new insights into the potential consequences of SNZVI
      treatments on the metal Cd immobilization in contaminated river sediments.

PMID- 27693996
TI  - Adverse childhood experiences, health, and employment: A study of men seeking job
      services.
AB  - The present study explored factors associated with barriers to current employment
      among 199 low-income, primarily Black American men seeking job services. The
      study took place in an urban setting located within the upper Midwest region of
      the U.S., where the problem of Black male joblessness is both longstanding and
      widespread. Recent research suggests that Black male joblessness regionally and
      nationally is attributable to myriad macro- and micro-level forces. While
      structural-level factors such as migration of available jobs, incarceration
      patterns, and racism have been relatively well-studied, less is known about
      individual-level predictors of Black male joblessness, which are inextricably
      linked to macro-level or structural barriers. This study therefore examined
      relations between adverse childhood experiences (ACEs), health-related factors,
      and employment-related problems. Participants faced both specific and cumulative
      childhood adversities at much higher rates than men from more economically
      advantaged contexts. In addition, the physical, behavioral, and mental health of
      the study participants were, according to self-report survey results, notably
      worse than that of the general population or alternative samples. Finally,
      results indicated that exposure to ACEs may have helped to undermine the men's
      ability to attain current employment and that drug problems along with depression
      symptoms helped explain the link between ACEs and employment barriers.
      Theoretical and practical implications of results are explored.

PMID- 27693997
TI  - Mental rotation and working memory in musicians' dystonia.
AB  - BACKGROUND: Mental rotation of body parts engages cortical-subcortical areas that
      are actually involved in the execution of a movement. Musicians' dystonia is a
      type of focal hand dystonia that is grouped together with writer's cramp under
      the rubric of "occupational dystonia", but it is unclear to which extent these
      two disorders share common pathophysiological mechanisms. Previous research has
      demonstrated patients with writer's cramp to have deficits in mental rotation of
      body parts. It is unknown whether patients with musicians' dystonia would display
      similar deficits, reinforcing the concept of shared pathophysiology. METHODS:
      Eight patients with musicians' dystonia and eight healthy musicians matched for
      age, gender and musical education, performed a number of tasks assessing mental
      rotation of body parts and objects as well as verbal and spatial working memories
      abilities. RESULTS: There were no differences between patients and healthy
      musicians as to accuracy and reaction times in any of the tasks. CONCLUSIONS:
      Patients with musicians' dystonia have intact abilities in mentally rotating body
      parts, suggesting that this disorder relies on a highly selective disruption of
      movement planning and execution that manifests only upon playing a specific
      instrument. We further demonstrated that mental rotation of body parts and
      objects engages, at least partially, different cognitive networks.

PMID- 27693998
TI  - Erratum to "Impaired executive functions in subjects with frequent nightmares as
      reflected by performance in different neuropsychological tasks" [Brain Cognit. 78
      (2012) 274-283].

PMID- 27693999
TI  - Predictive action tracking without motor experience in 8-month-old infants.
AB  - A popular idea in cognitive neuroscience is that to predict others' actions,
      observers need to map those actions onto their own motor repertoire. If this is
      true, infants with a relatively limited motor repertoire should be unable to
      predict actions with which they have no previous motor experience. We
      investigated this idea by presenting pre-walking infants with videos of upright
      and inverted stepping actions that were briefly occluded from view, followed by
      either a correct (time-coherent) or an incorrect (time-incoherent) continuation
      of the action (Experiment 1). Pre-walking infants looked significantly longer to
      the still frame after the incorrect compared to the correct continuations of the
      upright, but not the inverted stepping actions. This demonstrates that motor
      experience is not necessary for predictive tracking of action kinematics. In a
      follow-up study (Experiment 2), we investigated sensorimotor cortex activation as
      a neural indication of predictive action tracking in another group of pre-walking
      infants. Infants showed significantly more sensorimotor cortex activation during
      the occlusion of the upright stepping actions that the infants in Experiment 1
      could predictively track, than during the occlusion of the inverted stepping
      actions that the infants in Experiment 1 could not predictively track. Taken
      together, these findings are inconsistent with the idea that motor experience is
      necessary for the predictive tracking of action kinematics, and suggest that
      infants may be able to use their extensive experience with observing others'
      actions to generate real-time action predictions.

PMID- 27694001
TI  - Relevance of carnosic acid to the treatment of several health disorders:
      Molecular targets and mechanisms.
AB  - Carnosic acid is a phenolic diterperne compound found in abundance in sage and
      rosemary, which are both widely used in traditional medicine. Research over the
      past decade indicates that carnosic acid has multiple bioactive properties
      including antioxidant, anti-inflammatory and anticancer activities among others.
      This review summarizes the current in vitro and in vivo data about the efficacy
      of carnosic acid in the prevention or treatment of various experimental health
      disorders. The analysis of the literature allows an insight into the
      participation of numerous signaling pathways modulated by carnosic acid, into its
      synergistic potential and, thus, into the divergence in cellular mechanisms of
      action of this molecule.

PMID- 27694000
TI  - Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in
      diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities.
AB  - The present study investigated the protective effect of quercetin (Querc) on
      memory, anxiety-like behavior and impairment of ectonucleotidases and
      acetylcholinesterase (AChE) activities in brain of streptozotocin-induced
      diabetic rats (STZ-diabetes). The type 1 diabetes mellitus was induced by an
      intraperitoneal injection of 70mg/kg of streptozotocin (STZ), diluted in 0.1M
      sodium-citrate buffer (pH 4.5). Querc was dissolved in 25% ethanol and
      administered by gavage at the doses of 5, 25 and 50mg/kg once a day during
      40days. The animals were distributed in eight groups of ten animals as follows:
      vehicle, Querc 5mg/kg, Querc 25mg/kg, Querc 50mg/kg, diabetes, diabetes plus
      Querc 5mg/kg, diabetes plus Querc 25mg/kg and diabetes plus Querc 50mg/kg. Querc
      was able to prevent the impairment of memory and the anxiogenic-like behavior
      induced by STZ-diabetes. In addition, Querc prevents the decrease in the NTPDase
      and increase in the adenosine deaminase (ADA) activities in SN from cerebral
      cortex of STZ-diabetes. STZ-diabetes increased the AChE activity in SN from
      cerebral cortex and hippocampus. Querc 50mg/kg was more effective to prevent the
      increase in AChE activity in the brain of STZ-diabetes. Querc also prevented an
      increase in the malondialdehyde levels in all the brain structures. In
      conclusion, the present findings showed that Querc could prevent the impairment
      of the enzymes that regulate the purinergic and cholinergic extracellular
      signaling and improve the memory and anxiety-like behavior induced by STZ
      diabetes.

PMID- 27694003
TI  - Differential role of microRNAs in prognosis, diagnosis, and therapy of ovarian
      cancer.
AB  - Ovarian cancer (OC) is the most lethal of malignant gynecological cancers, and
      has a very poor prognosis, frequently, attributable to late diagnosis and
      responsiveness to chemotherapy. In spite of the technological and medical
      approaches over the past four decades, involving the progression of several
      biological markers (mRNA and proteins biomarkers), the mortality rate of OC
      remains a challenge due to its late diagnosis, which is expressly ascribed to low
      specificities and sensitivities. Consequently, there is a crucial need for novel
      diagnostic and prognostic markers that can advance and initiate more
      individualized treatment, finally increasing survival of the patients. MiRNAs are
      non-coding RNAs that control target genes post transcriptionally. They are
      included in tumorigenesis, apoptosis, proliferation, invasion, metastasis, and
      chemoresistance. Several studies have within the last decade demonstrated that
      miRNAs are dysregulated in OC and have possibilities as diagnostic and prognostic
      biomarkers for OC. Additionally; recent studies have also focused on miRNAs as
      predictors of chemotherapy sensitivities and their potential as therapeutic
      targets. In this review, we discuss the current data involving the accumulating
      evidence of the altered expression of miRNAs in OC, their role in diagnosis,
      prognosis, and forecast of response to therapy. Given the heterogeneity of this
      disease, it is likely that advances in long-term survival might be also attained
      by translating the recent insights of miRNAs participation in OC into new
      targeted therapies that will have a crucial effect on the management of ovarian
      cancer.

PMID- 27694002
TI  - Down-regulation of microRNA-338-3p promoted angiogenesis in hepatocellular
      carcinoma.
AB  - miRNAs are involved in substantial biological passways, including tumorigenesis,
      cancer development and progression. Angiogenesis plays a vital role in the
      progression of hepatocellular carcinoma (HCC), and VEGF is closely associated
      with the angiogenesis. However, the molecular mechanism of miRNAs in regulation
      tumorigenesis of HCC remains to be investigated. In the present research, we
      confirmed that miR-338-3p was suppressed both in HCC tissues and HCC cell lines.
      Then the tube formation, transwell and Chorioallantoic membrane (CAM) assay were
      carried out, such indicated that down-regulation of miR-338-3p can sharply
      increased, while up-regulation drastically suppressed angiogenesis of HCC cells
      in vitro. Moreover, MACC1 is predicted to be a target of miR-338-3p and we
      checked the prediction through luciferase assay. And then, our research showed
      that negative correlation existed between miR-338-3p and MACC1, beta-catenin and
      VEGF that has been reported participated in cancer behavior in HCC cell lines.
      Subsequently, our assays illustrated that suppression miR-338-3p can up-regulate
      MACC1, beta-catenin and VEGF expression of HCC cells. In conclusion, our research
      discovered that miR-338-3p can contribute to HCC angiogenesis by targeting MACC1,
      beta-catenin and VEGF.

PMID- 27694004
TI  - Odontogenic ameloblast-associated protein (ODAM) inhibits human colorectal cancer
      growth by promoting PTEN elevation and inactivating PI3K/AKT signaling.
AB  - Odontogenic ameloblast-associated protein (ODAM), an acidic matricellular
      protein, has been implicated in several epithelial neoplasms. However, its
      biological functions and molecular mechanisms in cancer progression, particular
      colorectal carcinoma (CRC), remain unknown. Here we demonstrated that ODAM was
      significantly down-regulated in CRC tissues compared with their normal
      counterparts. Then, we established that ODAM expression level was closely
      correlated with CRC development and patient prognosis. The abnormal expression of
      ODAM dramatically affected CRC cell growth in vitro and in vivo. We further
      revealed that the inhibitory effects of ODAM on CRC cell growth were associated
      with PTEN elevation and PI3K/AKT signaling inactivation. Furthermore, we
      determined that silencing of PTEN expression yielded recovery of AKT activity in
      ODAM-expressing CRC cells. Our study suggests matricellular protein ODAM may
      serve as a novel prognostic marker and act as a CRC growth suppressor.

PMID- 27694005
TI  - Enhanced miR-9 promotes laryngocarcinoma cell survival via down-regulating PTEN.
AB  - MicroRNAs (miRNAs) play important roles in gene regulation during
      laryngocarcinoma. MiR-9 is a potential oncomiR, but its function in
      laryngocarcinoma is not known. The aim of this study is to investigate the roles
      of miR-9 in laryngocarcinoma. We found miR-9 expression was higher in
      laryngocarcinoma tissues compared with their normal controls, so did the
      laryngocarcinoma cells. Cellular function of miR-9 indicated that miR-9
      restoration in laryngocarcinoma cells could promote cell proliferation and
      metastasis. Phosphatase and tensin homolog (PTEN) was predicted as a target gene
      of miR-9 and verified using luciferase reporter assay. PTEN expression was down
      regulated in the laryngocarcinoma cells with miR-9 overexpression. We also found
      that miR-9 expression was negatively associated with PTEN expression in
      laryngocarcinoma tissues.

PMID- 27694007
TI  - Morin inhibits cell proliferation and fibronectin accumulation in rat glomerular
      mesangial cells cultured under high glucose condition.
AB  - Morin, is a natural bioflavonoid isolated from Chinese herbs of the Moraceae
      family, has been reported to possess antidiabetic activity. However, the role of
      morin on glomerular mesangial cells (MCs) proliferation and extracellular matrix
      (ECM) accumulation in diabetic condition is still unclear. Therefore, in this
      study, we investigated the role of morin on cell proliferation and ECM
      accumulation in rat glomerular MCs cultured under high glucose (HG) condition.
      Our results showed that morin inhibited HG-induced MC proliferation, arrested HG
      induced cell-cycle progression, reversed HG-inhibited expression of p21Waf1/Cip1
      and p27Kip1. It also inhibited HG-induced ECM expression, ROS generation and NOX4
      expression in MCs. Furthermore, morin suppressed HG-induced phosphorylation of
      p38 MAPK and JNK1/2 in MCs. These data suggest that morin inhibits HG-induced MC
      proliferation and ECM expression through suppressing the activation of p38 MAPK
      and JNK signaling pathways. Thus, morin may be useful for the prevention or
      treatment of diabetic nephropathy.

PMID- 27694006
TI  - Cytotoxic and antioxidative potentials of ethanolic extract of Eugenia uniflora
      L. (Myrtaceae) leaves on human blood cells.
AB  - Eugenia uniflora is used in the Brazilian folk medicine to treat intestinal
      disorders and hypertension. However, scanty information exist on its potential
      toxicity to human, and little is known on its antioxidant activity in biological
      system. Hence, we investigated for the first time the potential toxic effects of
      ethanolic extract (EtOH) of E. uniflora (EEEU) in human leukocytes and
      erythrocytes, as well as its influence on membrane erythrocytes osmotic
      fragility. In addition, EEEU was chemically characterized and its antioxidant
      capacity was evaluated. We found that EEEU (1-480MUg/mL) caused neither
      cytotoxicity nor DNA damage evaluated by Trypan blue and Comet assay,
      respectively. EEEU (1-480MUg/mL) did not have any effect on membrane erythrocytes
      fragility. In addition, EEEU inhibited Fe2+-induced lipid peroxidation in rat
      brain and liver homogenates, and scavenged the DPPH radical. EEEU presented some
      polyphenolic compounds with high content such as quercetin, quercitrin,
      isoquercitrin, luteolin and ellagic acid, which may be at least in part
      responsible for its beneficial effects. Our results suggest that consumption of
      EEEU at relatively higher concentrations may not result in toxicity. However,
      further in vitro and in vivo studies should be conducted to ascertain its safety.

PMID- 27694008
TI  - New potential phytotherapeutics obtained from white mulberry (Morus alba L.)
      leaves.
AB  - The present work demonstrates the profound and unique phyto-pharmacological and
      nutritional profile of white mulberry (Morus alba L.) leaves which containing
      considerable amounts of easy digestive proteins, carbohydrates, micro- and
      macronutrients, polyphenols, free amino acids, organic acids. The wide range of
      significant biopharmaceutical activities of the aqueous and polar organic
      solvents extracts from mulberry leaves - including antidiabetic, antibacterial,
      anticancer, cardiovascular, hypolipidemic, antioxidant, antiatherogenic, and anti
      inflammatory - have been critically discussed. The main objective was to
      demonstrate the results of recently published study on the components of white
      mulberry leaves exhibiting their biological activity in the various pathological
      and health human ailments. In addition, we intend to drawn the attention of
      researchers and public health workers for the extended exploration of this
      deciduous plant leaves as the source of potential indigenous nutraceuticals and
      functional food products to enable development of alternative prevention and
      treatment protocols offered in therapy of the common non-communicable diseases
      and malignances.

PMID- 27694010
TI  - Dualistic temperature sensing in Er3+/Yb3+ doped CaMoO4 upconversion phosphor.
AB  - Temperature sensing performance of Er3+/Yb3+ doped CaMoO4 phosphor prepared via
      polyol method is reported herein. The X-ray diffraction, Fourier transform
      infrared spectroscopy and field emission scanning electron microscopy are done to
      confirm the phase, structure and purity of the synthesized phosphor. The infrared
      to green upconversion emission is investigated using 980nm diode laser excitation
      along with its dependence on input pump power and external temperature. The
      temperature dependent fluorescence intensity ratio of two upconversion emission
      bands assigned to 2H11/2->4I15/2 (530nm) and 4S3/2->4I15/2 (552nm) transitions
      has shown two distinct slopes in the studied temperature range - 300 to 760K and
      therefore, dual nature of temperature sensitivity is observed in this phosphor.
      This phenomenon in rare earth doped materials is either scarcely reported or
      overlooked. The material has shown higher sensitivity in the high temperature
      region (535K<T<760K) with a maximum of 7.21*10-3K-1 at 535K. The results indicate
      potential of CaMoO4: Er3+/Yb3+ phosphor in high temperature thermometry.

PMID- 27694009
TI  - Involvement of metabolites in early defense mechanism of oil palm (Elaeis
      guineensis Jacq.) against Ganoderma disease.
AB  - Understanding the mechanism of interaction between the oil palm and its key
      pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen
      leads to a major loss of revenue in leading palm oil producing countries in
      Southeast Asia. Here in this study, we assess the morphological and biochemical
      changes in Ganoderma disease infected oil palm seedling roots in both resistant
      and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were
      applied as a source of inoculum to artificially infect the roots of resistant and
      susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to
      measure an array of plant metabolites in 100 resistant and susceptible oil palm
      seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical
      effects, univariate and multivariate analyses were used to identify key-Ganoderma
      disease associated metabolic agitations in both resistant and susceptible oil
      palm root tissues. Ganoderma disease related defense shifts were characterized
      based on (i) increased antifungal activity in crude extracts, (ii) increased
      lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny,
      (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline,
      pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol
      (iv) degraded cortical cell wall layers, possibly resulting from fungal
      hydrolytic enzyme activity needed for initial penetration. The present study
      suggested that plant metabolites mainly lipids and heterocyclic aromatic organic
      metabolites could be potentially involved in early oil palm defense mechanism
      against G. boninense infection, which may also highlight biomarkers for disease
      detection, treatment, development of resistant variety and monitoring.

PMID- 27694011
TI  - High-pressure Raman study of Terephthalonitrile.
AB  - The in situ high-pressure Raman spectra of Terephthalonitrile (TPN) have been
      investigated from ambient to 12.6GPa at room temperature. All the fundamental
      vibrational modes of TPN at ambient were assigned based on the first-principle
      calculations. A detailed Raman spectroscopy analysis revealed that TPN underwent
      a phase transition at ~5.3GPa. The frequencies of the TPN Raman peaks increase
      with increasing the pressure which can be attributed to the reduction in the
      interatomic distances and the escalation of effective force constants. The
      intensity of the C-C-C ring-out-plane deformation mode increases gradually as the
      frequency remains almost constant during the compression which can be explained
      by the existence of pi-pi interactions in TPN molecules. Additionally, the
      pressure-induced structural changes of TPN on the Fermi resonance between the C=N
      out-of-plane vibration mode and the C-CN out-of-plane vibration mode have been
      analyzed.

PMID- 27694013
TI  - Elevated serum miR-106b and miR-146a in patients with focal and generalized
      epilepsy.
AB  - BACKGROUND: Epilepsy is a chronic neurological disorder characterized by
      recurring seizures. Although scalp electroencephalograms (EEG) and neuroimaging
      have been used in clinical diagnosis of epilepsy, the more economical, rapid and
      non-invasive biomarker is still desirable, contributing to the accurate clinical
      diagnosis and facilitating the appropriate treatment. METHODS: The expression of
      four epilepsy-associated miRNAs (miR-106b, miR-146a, miR-194-5p and miR-301a) was
      measured by quantitative RT-PCR in the serum of 90 epilepsy patients and control
      populations. RESULTS: It was found that the serum miR-106b, miR-146a and miR-301a
      were significantly increased but serum miR-194-5p was significantly decreased in
      epilepsy patients compared with healthy control populations. In addition, serum
      miR-106b (r=0.6412) and miR-146a (r=0.5896) were correlated with NHS3 score in
      epilepsy patients. Furthermore, the ROC result of serum miR-106b for prediction
      of epilepsy was 0.786, higher than those of serum miR-146a (AUC=0.774), miR-194
      (AUC=0.686) or miR-310a (AUC=0.696). The combination of serum miR-106b and miR
      146a gained a better sensitivity/specificity for prediction of epilepsy
      (AUC=0.887). CONCLUSION: Our preliminary findings indicate that upregulated serum
      miR-106b and miR-146a might be a potential biomarker for epilepsy evaluation.

PMID- 27694012
TI  - Methyl jasmonate elicits the biotransformation of geraniol stored as its glucose
      conjugate into methyl geranate in Achyranthes bidentata plant.
AB  - To investigate the biotransformation pathway of airborne geraniol by Achyranthes
      bidentata (A. bidentata), deuterium labeled geraniol was applied with or without
      methyl jasmonate (MeJA), and the biosynthesized metabolites were analyzed. In A.
      bidentata leaves, geraniol was conjugated with glucose. The conjugate was then
      metabolized to afford methyl geranate only under MeJA elicitation. MeJA elicits
      the biotransformation of geraniol into methyl geranate by inducing the conversion
      of the intermediate, glucose conjugate of geraniol.

PMID- 27694014
TI  - Status epilepticus in the elderly-A retrospective study on 120 patients.
AB  - PURPOSE: Status epilepticus (SE) is one of the most common neurological
      emergencies with a high incidence in the elderly. Major determinants of prognosis
      are patients' age, duration of SE and underlying etiology. We aimed identifying
      differences in clinical presentation of SE, etiologies and outcome between
      patients (pts.) sixty years or older (>=60) and younger than sixty (<60) years
      (yrs). METHODS: We retrospectively analyzed 120 patients (48 women) with SE
      admitted to the Neurological Intensive Care Unit (NICU), Department of Neurology,
      Paracelsus Medical University Salzburg, Austria between 1/2011 and 01/2013. KEY
      FINDINGS: Median age was 69 years (range 14-90) (63% >=60yrs). Generalized tonic
      clonic SE was the most common SE type, whereas non convulsive SE with and without
      coma tended to occur more frequently in the elderly (33% >=60 yrs. vs. 20%<60
      yrs, Chi2=3.511, p=0.061). Preexisting history of epilepsy was more common in the
      younger age group (64% vs 41% p=0.014). An acute symptomatic cause of SE was
      identified in 25% (31/120), with cerebrovascular diseases being more frequent in
      the elderly (47% vs. 11%; p<0.01). Duration of SE did not differ between the age
      groups (p=0.63). Mortality was higher in elderly patients (31% vs. 7%, p=0.028,
      Chi Square=5.18) and moderate disability in younger patients (42% vs 17%;
      p=0.005, Chi Square=7.83). After Bonferroni correction only the higher rate of
      cerebrovascular etiologies in the elderly was statistically significant.
      SIGNIFICANCE: In the elder population, SE occurs more often in patients without
      preexisting epilepsy and is most frequently caused by cerebrovascular diseases.
      NCSE tends to be more frequent in the elderly and diagnosis is complicated by
      subtle clinical presentation. Even though comorbidities represent treatment
      limitations, in our sample no differences in choice of AED as well as dosage were
      observed between the age groups, reflecting a trend toward AEDs with more
      favorable adverse event profile in all patients. SE in older patients is
      associated with poorer outcome and higher mortality.

PMID- 27694015
TI  - Local deformation behavior of surface porous polyether-ether-ketone.
AB  - Surface porous polyether-ether-ketone has the ability to maintain the tensile
      monotonic and cyclic strength necessary for many load bearing orthopedic
      applications while providing a surface that facilitates bone ingrowth; however,
      the relevant deformation behavior of the pore architecture in response to various
      loading conditions is not yet fully characterized or understood. The focus of
      this study was to examine the compressive and wear behavior of the surface porous
      architecture using micro Computed Tomography (micro CT). Pore architectures of
      various depths (~0.5-2.5mm) and pore sizes (212-508um) were manufactured using a
      melt extrusion and porogen leaching process. Compression testing revealed that
      the pore architecture deforms in the typical three staged linear elastic,
      plastic, and densification stages characteristic of porous materials. The
      experimental moduli and yield strengths decreased as the porosity increased but
      there was no difference in properties between pore sizes. The porous architecture
      maintained a high degree of porosity available for bone-ingrowth at all strains.
      Surface porous samples showed no increase in wear rate compared to injection
      molded samples, with slight pore densification accompanying wear.

PMID- 27694016
TI  - Reading ability reflects individual differences in auditory brainstem function,
      even into adulthood.
AB  - Research with developmental populations suggests that the maturational state of
      auditory brainstem encoding is linked to reading ability. Specifically, children
      with poor reading skills resemble biologically younger children with respect to
      their auditory brainstem responses (ABRs) to speech stimulation. Because ABR
      development continues into adolescence, it is possible that the link between ABRs
      and reading ability changes or resolves as the brainstem matures. To examine
      these possibilities, ABRs were recorded at varying presentation rates in adults
      with diverse, yet unimpaired reading levels. We found that reading ability in
      adulthood related to ABR Wave V latency, with more juvenile response morphology
      linked to less proficient reading ability, as has been observed for children.
      These data add to the evidence indicating that auditory brainstem responses serve
      as an index of the sound-based skills that underlie reading, even into adulthood.

PMID- 27694018
TI  - Substance flow analysis and environmental releases of PBDEs in life cycle of
      automobiles.
AB  - Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants,
      have been widely used in many applications in industry such as automobiles,
      textiles, and electronics. This study focused on a quantitative substance flow
      analysis (SFA) of PBDEs in automobiles in order to identify their flow by life
      cycle and treatment pathways of PBDEs-containing materials in end-of-life
      vehicles (ELVs) in Korea. In addition, this study has estimated environmental
      releases of PBDEs in automobiles by life cycle in Korea. During this study, PBDEs
      were analyzed for the samples collected from several ELVs treatment facilities
      using X-ray fluorescence and gas chromatography/mass spectrometry (GC/MS)
      methods. The system boundary for SFA of PBDEs ranged from manufacturing/trade to
      disposal stage of automobiles by life cycle. Based on the result of the SFA, it
      was found that the amount of PBDEs in automobiles were the highest in use stage
      (7748ton/year), followed by production stage (1743ton/year) in 2014. In disposal
      stage, automobile shredded residues (ASR) and seat fabrics were the main
      components with relatively high levels of PBDEs in ELVs. The major treatment
      methods of such components included incineration (84%), energy recovery (9%), and
      landfilling (6%). This research indicates that PBDEs were emitted the highest
      amount from interior components during the use stage of automobiles, followed by
      recycling processes such as dismantling and shredding. This study suggests that
      PBDEs in ASR and seat fabrics should be properly managed to prevent the
      widespread dispersion in the environment.

PMID- 27694019
TI  - Promotion of enamel caries remineralization by an amelogenin-derived peptide in a
      rat model.
AB  - OBJECTIVE: An amelogenin-derived peptide has been shown to promote
      remineralization of demineralized enamel in an in vitro model of initial caries
      induced by pH cycling. The present study examines whether the peptide exerts
      similar effects within the complex oral environment in vivo. DESIGN: Specific
      pathogen-free Sprague-Dawley rats (n=36) were infected with Streptococcus mutans,
      given ad libitum access to Diet 2000 and drinking water supplemented with sucrose
      (10%, w/v), and then randomly divided into three groups treated with 25MUM
      peptide solution, 1g/L NaF or deionized water. Molar teeth were swabbed twice
      daily with the respective solutions for 24days. Then animals were killed, their
      jaws were removed and caries lesions were analyzed using the quantitative light
      induced fluorescence-digital (QLF-D) technique to measure changes in mineral
      content. To verify QLF-D results, caries were scored for lesion depth and size
      using the Keyes method, and analyzed using polarized light microscopy (PLM).
      RESULTS: Mineral gain was significantly higher in teeth treated with peptide or
      NaF than in teeth treated with water (p<0.05), based on the QLF-D results (DeltaF
      and DeltaQ). Incidence of smooth-surface and sulcal caries based on Keyes scores
      was similar in rats treated with peptide or NaF, and significantly lower in these
      groups than in rats treated with water (p<0.05). Lesions on teeth treated with
      peptide or NaF were shallower, based on PLM. No significant differences were
      observed between molar enamel caries treated with peptide or NaF. CONCLUSIONS:
      This amelogenin-derived peptide can promote remineralization in a rat caries
      model, indicating strong potential for clinical use.

PMID- 27694017
TI  - Subjective experience of inner speech in aphasia: Preliminary behavioral
      relationships and neural correlates.
AB  - Many individuals with aphasia describe anomia with comments like "I know it but I
      can't say it." The exact meaning of such phrases is unclear. We hypothesize that
      at least two discrete experiences exist: the sense of (1) knowing a concept, but
      failing to find the right word, and (2) saying the correct word internally but
      not aloud (successful inner speech, sIS). We propose that sIS reflects successful
      lexical access; subsequent overt anomia indicates post-lexical output deficits.
      In this pilot study, we probed the subjective experience of anomia in 37 persons
      with aphasia. Self-reported sIS related to aphasia severity and phonological
      output deficits. In multivariate lesion-symptom mapping, sIS was associated with
      dorsal stream lesions, particularly in ventral sensorimotor cortex. These
      preliminary results suggest that people with aphasia can often provide meaningful
      insights about their experience of anomia and that reports of sIS relate to
      specific lesion locations and language deficits.

PMID- 27694020
TI  - 4-Hydroxyphenylacetic acid oxidation in sulfate and real olive oil mill
      wastewater by electrochemical advanced processes with a boron-doped diamond
      anode.
AB  - The degradation of 4-hydroxyphenylacetic acid, a ubiquitous component of olive
      oil mill wastewater (OOMW), has been studied by anodic oxidation with
      electrogenerated H2O2 (AO-H2O2), electro-Fenton (EF) and photoelectro-Fenton
      (PEF). Experiments were performed in either a 0.050M Na2SO4 solution or a real
      OOMW at pH 3.0, using a cell with a boron-doped diamond (BDD) anode and an air
      diffusion cathode for H2O2 generation. Hydroxyl radicals formed at the BDD
      surface from water oxidation in all processes and/or in the bulk from Fenton's
      reaction between added Fe2+ and generated H2O2 in EF and PEF were the main
      oxidants. In both matrices, the oxidation ability of the processes increased in
      the order AO-H2O2<EF<PEF. The superiority of PEF was due to the photolytic action
      of UVA radiation on photosensitive by-products, as deduced from the quick removal
      of Fe(III)-oxalate complexes. The effect of current density and organic content
      on the performance of all treatments was examined. 4-Hydroxyphenylacetic acid
      decay obeyed a pseudo-first-order kinetics. The PEF treatment of 1.03mM 4
      hydroxyphenylacetic acid in 0.050M Na2SO4 allowed 98% mineralization at 360min
      even at low current density, whereas 80% mineralization and a significant
      enhancement of biodegradability were achieved with the real OOMW.

PMID- 27694021
TI  - Acidic horseradish peroxidase activity abolishes genotoxicity of common dyes.
AB  - The aim of this study was to investigate the impact of dyes on DNA before and
      after enzymatic decolorization by acidic horseradish peroxidase (HRP-A). The
      comet assay is easy and feasible method widely used to measure DNA damage and
      repair. The medium-throughput comet assay was employed for assessment of
      genotoxic effects of 8 dyes in BEAS-2B cells. We have incorporated a digestion
      with bacterial endonuclease (formamidopyrimidine DNA glycosylase, FPG) to detect
      oxidized bases in the case of single and double azo dyes, Orange II (OR2) and
      Amido Black 10B (AB), respectively. This allowed detection 8-oxo-7,8
      dihydroguanine, one of most abundant oxidized bases in nuclear DNA. In the case
      of AB there was no indication of DNA damage, either strand brakes or FPG
      sensitive sites before and after decolorization. The OR2 induced DNA damage (in
      terms of percentage of DNA in comet tails). Also, the frequency of FPG-sensitive
      sites increased with OR2 concentration. After decolorization no DNA damaging
      effects was seen at all. The interaction studies of OR2 and AB, before and after
      decolorization, with calf thymus DNA has been investigated by absorption and
      fluorescence spectroscopy. The results provide support for the idea that in some
      cases enzymatic decolorization contributes to lower genotoxicity potential.

PMID- 27694022
TI  - Bioremediation of the neonicotinoid insecticide clothianidin by the white-rot
      fungus Phanerochaete sordida.
AB  - Clothianidin (CLO) is a member of the neonicotinoid pesticides, which have been
      widely used worldwide over the last two decades. However, its toxicity for bees
      and neurological toxicity for humans are urgent problems. Here, the degradation
      of CLO by the white-rot fungus Phanerochaete sordida was examined in nitrogen
      limited liquid medium. After incubation for 20days at 30 degrees C, 37% of CLO
      was degraded in the cultures. High-resolution ESI-MS and NMR analyses of the
      culture supernatant identified N-(2-chlorothiazol-5-yl-methyl)-N'-methylurea
      (TZMU) as a metabolite of CLO degradation. The addition of cytochrome P450
      inhibitors to the culture medium markedly reduced the degradation of CLO by P.
      sordida. And manganese peroxidase, a major ligninolytic enzyme secreted by this
      fungus, were not carried out CLO degradation. The effects of CLO and TZMU on the
      viability of the neuronal cell line Neuro2a demonstrated that P. sordida
      effectively degrades CLO into a metabolite that lacks neurotoxicity.

PMID- 27694023
TI  - Bioaccumulation and bound-residue formation of 14C-decabromodiphenyl ether in an
      earthworm-soil system.
AB  - Decabromodiphenyl ether (DecaBDE) is one of the most frequently detected flame
      retardants in terrestrial environments. However, the fate of DecaBDE and its
      transport in an earthworm-soil system with and without a DecaBDE-degrading strain
      have rarely been evaluated. In this study, 14C-DecaBDE was self-synthesized, and
      a DBDE-degrading strain, Rhodococcus erythropolis, was used in an earthworm-soil
      system. DecaBDE showed limited degradation and mineralization after 35days of all
      treatments. The bound-residue (BR) formation in soil was <2.5% in the system
      containing earthworms, which was significantly higher (p<0.05) than that observed
      in the absence of earthworms (<0.45%). DecaBDE could be adsorbed by the
      earthworms with a BSAF of <=0.31. The distribution of 14C-DecaBDE concentrations
      in the earthworm roughly followed the pattern of crop gizzard>digestive
      system>head>tail>body wall, suggesting that DecaBDE was mainly uptaken through
      ingestion. Up to 31% of the 14C-DecaBDE in the earthworms was not extractable,
      revealing that the total concentration of accumulated 14C-DecaBDE was
      underestimated. The results also showed that the presence of DecaBDE-degrading
      bacteria did not significantly affect the fate of DecaBDE and its accumulation in
      earthworms. The study indicates that the conventional assessment of the
      bioaccumulation and ecological effects of DecaBDE, which is based only on
      extractable concentrations, may underestimate the risks.

PMID- 27694024
TI  - Toxicity assessment of carbon black waste: A by-product from oil refineries.
AB  - In Singapore, approximately 30t/day of carbon-based solid waste are produced from
      petrochemical processes. This carbon black waste has been shown to possess
      physical properties that are characteristic of a good adsorbent such as high
      external surface area. Therefore, there is a growing interest to reutilize and
      process this carbon black waste into secondary materials such as adsorbents.
      However, the carbon black waste obtained from petrochemical industries may
      contain heavy metals that are hazardous to human health and the environment,
      hence restricting its full potential for re-utilization. Therefore, it is
      important to examine the possible toxicity effects and toxicity mechanism of
      carbon black waste on human health. In this study, inductively coupled plasma
      optical emission spectroscopy (ICP-OES) analysis showed that the heavy metals,
      vanadium (V), molybdenum (Mo) and nickel (Ni), were present in the carbon black
      waste in high concentrations. Three human cell lines (HepG2 cells, MRC-5 cells
      and MDA-MB-231 cells) were used to investigate the toxicity of carbon black waste
      extract in a variety of in vitro assays. Results from MTS assays indicated that
      carbon black waste extract decreased the viability of all three cell lines in a
      dose and time-dependent manner. Observations from confocal microscopy further
      confirmed this phenomenon. Flow cytometry assay also showed that carbon black
      waste extract induced apoptosis of human cell lines, and the level of apoptosis
      increased with increasing waste concentration. Results from reactive oxygen
      species (ROS) assay indicated that carbon black waste extract induced oxidative
      stress by increasing intracellular ROS generation in these three human cell
      lines. Moreover, induction of oxidative damage in these cells was also observed
      through the alteration of glutathione (GSH) and superoxide dismutase (SOD)
      activities. Last but not least, by treating the cells with V-spiked solution of
      concentration equivalent to that found in the carbon black waste extract, V was
      identified as the main culprit for the high toxicity of carbon black waste
      extract. These findings could potentially provide insight into the hazards of
      carbon black waste extract and its toxicity mechanism on human cell lines.

PMID- 27694025
TI  - Efficient adsorption and antibacterial properties of electrospun CuO-ZnO
      composite nanofibers for water remediation.
AB  - On the face of impending global water resources, developing low-cost and
      efficient water treatment technologies and materials thereof is highly important.
      Herein, we explore the adsorption capacity and antibacterial properties of CuO
      ZnO (CZ) composite nanofibers. The ultrafine nanofibers were fabricated using
      simple and inexpensive electrospinning technique and were further characterized
      using Field Emission-Scanning Electron Microscope (FE-SEM), Transmission electron
      microscope (TEM) and X-Ray Diffraction (XRD), Thermogravimetric analysis (TGA),
      Fourier transform Infrared Spectroscopy (FTIR). When employed as nanoadsorbents,
      CZ nanofibers exhibited excellent adsorption capacity for congo red dye.
      Adsorption Isotherms and kinetics were performed to determine the maximum
      adsorption capacity and the rate of adsorption, respectively, depicting the
      better efficiency of composite nanofibers as compared to their single
      counterparts. The mechanism of adsorption is also proposed with the evaluation of
      diffusion studies. The second part of this study deals with the examination of
      antibacterial activity of CZ composite nanofibers against antibiotic resistant
      GFP-E.coli and S. aureus. The antibacterial efficacy was monitored by visual
      turbidity assay, SEM analysis and reactive oxygen species (ROS) determination.
      Hence, such nanofibers have been explored as a single platform for the removal of
      biological as well organic contaminants so as to make them potential in the field
      of water remediation.

PMID- 27694026
TI  - Cr(VI) removal via anion exchange on a silver-triazolate MOF.
AB  - Gram-scale synthesis of a silver-triazolato framework - {[Ag8(tz)6](NO3)2.6H2O}n
      (1-NO3; tz-=3,5-diphenyl-1,2,4-triazolate) - has been achieved, enabling the
      systematic investigation of its anion-exchange properties. Our experimental
      results show that the anion-exchange pattern of 1-NO3 conforms to the so-called
      Hofmeister bias, which has been correlated to the hydrophobic nature of the MOF
      pores, and can be understood by considering the difference between the hydration
      energies of the exchanging anions. Furthermore, 1-NO3 displays a fast, efficient,
      and reversible adsorption of HCrO4- (via anion-exchange) from Cr(VI)-containing
      aqueous solution (Qmax=37.0 Cr mg/g, 303K), rendering it a promising prototype of
      a recyclable MOF for Cr(VI) removal.

PMID- 27694027
TI  - Increased photocatalytic activity of NiO and ZnO in photodegradation of a model
      drug aqueous solution: Effect of coupling, supporting, particles size and
      calcination temperature.
AB  - Mechanically ball-mill prepared clinoptilolite nanoparticles (NC) were used for
      increasing photocatalytic activity of NiO and ZnO as alone and binary systems.
      The semiconductors were supported onto the zeolite during calcination of Ni(II)
      Zn(II)-exchanged NC at different calcinations temperatures. XRD, FTIR, SEM-EDX, X
      ray mapping, DRS, TEM and BET techniques were used for characterization of the
      samples. The calcined catalysts at 400 degrees C for 4h showed the best
      photocatalytic activity for metronidazole (MNZ) in aqueous solution. The mole
      ratio of ZnO/NiO affected the photodegradation efficiency because activity of the
      coupled catalysts depends to the both e/h production and electron scavenging
      processes. In the used system, NiO acted as e/h production source and ZnO as an
      electron sink. Red shifts in band gaps of the supported coupled semiconductors
      was observed whit respect to monocomponent one, confirming formation of
      nanoparticles of the semiconductors onto the zeolitic bed. The best activities
      were obtained for the NiO1.3-ZnO1.5/NC (NZ-NC) and NiO0.7-ZnO4.3/NC (NZ3-NC)
      catalysts at pH 3, 1.2gL-1 of the catalysts and 1gL-1 of MNZ.

PMID- 27694028
TI  - Carbamazepine degradation by gamma irradiation coupled to biological treatment.
AB  - Carbamazepine is an emerging contaminant and resistant to biodegradation, which
      cannot be effectively removed by the conventional biological wastewater treatment
      processes. In this study, the combined gamma irradiation and biodegradation was
      employed to remove carbamazepine from wastewater. The effect of dose on the
      removal of carbamazepine was studied at different doses (300, 600 and 800Gy). The
      results showed that the removal efficiency of carbamazepine increased with dose
      increasing during the irradiation process. The maximum removal efficiency was
      99.8% at 800Gy, while the removal efficiency of total organic carbon (TOC) was
      only 26.5%. The removal efficiency of TOC increased to 79.3% after the sequent
      biological treatment. In addition, several intermediates and organic acids were
      detected. The possible degradation pathway of carbamazepine during the integrated
      irradiation and biodegradation was proposed. Based on the overall analysis, the
      combined gamma irradiation and biological treatment process can be an alternative
      for removing the recalcitrant organic pollutants such as carbamazepine from
      wastewater.

PMID- 27694029
TI  - Leaching mechanisms of constituents from fly ash under the influence of humic
      acid.
AB  - As a low-cost material for adsorption, FA is one of the most efficient adsorbents
      of HA. However, the leaching of elements from FA is problematic during
      utilization in water treatment. In this investigation, the potential leaching
      behaviors of Calcium, Arsenic, Born, Chromium, and other elements from FA in HA
      solution were studied via batch test. The data show that HA had an effect on the
      leaching of each element of FA, depending on the pH, the initial concentration of
      HA and the addition of calcium oxide (CaO). The Langmuir isotherm could better
      fit the equilibrium data in different initial concentrations of HA from 10 to
      100mg/L. Because of the interaction between HA and the FA leaching elements,
      multi-layer adsorption occurred when the initial concentration of HA was more
      than 100mg/L. The pH and free CaO content played major roles in HA adsorption and
      FA leaching. Using SEM and XRD to characterize the solid of FA being mixed with
      CaO treated in solution, the results demonstrated that the reaction between FA
      and CaO could generate crystal minerals, such as portlandite, gismondine,
      ettringite (AFt) and calcite, which effectively restrained the leaching of
      elements, reduced secondary pollution.

PMID- 27694030
TI  - Conception of a novel spray tower plasma-reactor in a spatial post-discharge
      configuration: Pollutants remote treatment.
AB  - This paper describes a novel gliding Arc discharge reactor producing a non
      thermal plasma at atmospheric pressure in humid air. The ionized gas is generated
      in a spray-tower absorber for the treatment of organic pollutants. The reactor
      configuration enables the plasma-degradation of micro-droplets effluents in the
      spatial post-discharge mode. This type of design allows to exclude the direct
      contact between the plasma plume and the liquid to be treated in order to avoid
      the liquid heating and the flame extinction problems. A hydrodynamic study
      coupling 'Navier-Stokes' equations and those of 'Convection-Diffusion' allowed to
      calculate the concentration profiles and the droplet falling velocity. The
      stripping of phenol was studied to valid the hydrodynamic approach. Experiences
      and simulations showed that after 1h of treatment, only 5% of the compound was
      transferred into the plasma phase. The spatiality of the novel reactor allowed a
      degradation rate of 100% for catechol after 38min of plasma-treatment. For 4
      nitrophenol, the degradation rate reached 90% after 120min. Phenol and its by
      products degradation were totally degraded by combining the spatiality of the
      reactor and the temporal post-discharge. A degradation mechanism was proposed and
      a plasmachemical reaction in relation with the pernitrous acid species was
      confirmed.

PMID- 27694031
TI  - Catheter-directed therapy as a first-line treatment strategy in hemodynamically
      unstable patients with acute pulmonary embolism: Yes or no?

PMID- 27694032
TI  - Cardiac palpitations: Are they due to subclinical takotsubo syndrome?

PMID- 27694033
TI  - Is the coronary artery myocardial "bridging" and left anterior descending
      "straightening" mediated by the myocardial wall motion abnormalities and edema in
      takotsubo syndrome?

PMID- 27694034
TI  - Comparison of standard and Lewis ECG in detection of atrioventricular
      dissociation in patients with wide QRS tachycardia.
AB  - BACKGROUND: The atrioventricular (AV) dissociation, which is frequently used in
      differential diagnosis of wide QRS complex tachycardia (WQCT), is the most
      specific finding of ventricular tachycardia (VT) with lower sensitivity. Herein,
      we aimed to show the importance of Lewis lead ECG records to detect 'visible p
      waves' during WQCT. METHOD: A total of 21 consecutive patients who underwent
      electrophysiologic study (EPS) were included in the study. During EPS, by using a
      quadripolar diagnostic catheter directed to the right ventricular apex, a fixed
      stimulus was given and the ventriculoatrial (VA) Wenkebach point was found, and a
      VT was simulated by a RV apical stimulus at 300ms. The standard and Lewis lead
      ECG records were taken during this procedure. RESULT: We detected 'visible p
      waves' in 7 (33.3%) and 14 (66.7%) patients in the standard and Lewis lead ECG
      groups, respectively. In terms of the 'visible p waves', there was a
      statistically significant difference between groups (p=0.022). The sensitivity of
      standard and Lewis lead ECG in determination of the visible p waves was 33.3% and
      66.7%, respectively. CONCLUSION: The Lewis lead ECG can be more informative about
      AV dissociation than the standard 12 lead ECG. As a result, we could suggest the
      assessment of the Lewis lead ECG recording in addition to the standard 12 lead
      ECG in differential diagnosis of VT in patients with WQCT.

PMID- 27694035
TI  - Absence of post-extrasystolic potentiation in takotsubo cardiomyopathy: Another
      piece of the puzzle?
AB  - BACKGROUND: Takotsubo cardiomyopathy (TCM) is an intriguing phenomenon
      characterized by transient and reversible left ventricular (LV) dysfunction
      despite angiographically unobstructed coronary arteries. The detailed
      pathophysiology of stunned, viable myocardium in TCM remains to be determined.
      Post-extrasystolic potentiation (PESP), the phenomenon of enhanced LV
      contractility following extrasystole, has been used to assess myocardial
      viability. METHODS: Utilizing a local database, we identified 74 cases that met
      the modified Mayo Clinic criteria for TCM between October 2004 and March 2016.
      The patients undergoing left ventriculography were assessed for the presence of
      fortuitously provoked extrasystoles and the presence or absence of PESP. RESULTS:
      The baseline characteristics of TCM were 93.2% female patients with median age of
      69 and majority cases were apical type (77%). In-hospital mortality was observed
      in 3 cases (4.1%), all of which were apical type. We observed improved ejection
      fraction after extrasystole compared to baseline, however stunned myocardium had
      minimal PESP whereas unaffected myocardium showed marked potentiation.
      CONCLUSION: Extrasystoles in TCM failed to elicit PESP in affected LV segments
      despite viability in those segments, in turn implicating a calcium handling
      abnormality in TCM. Potential explanations of our results may be that
      catecholamine excess caused maximum calcium release so that an extrasystole could
      not enhance contractility any further, or that there is a regional insensitivity
      to calcium release due to a disturbance of the calcium regulatory system at the
      molecular level despite the bolus of calcium availability provided by the
      extrasystole.

PMID- 27694036
TI  - Magnetic properties of single nanomagnets: Electron energy-loss magnetic chiral
      dichroism on FePt nanoparticles.
AB  - Electron energy-loss magnetic chiral dichroism (EMCD) allows for the
      quantification of magnetic properties of materials at the nanometer scale. It is
      shown that with the support of simulations that help to identify the optimal
      conditions for a successful experiment and upon implementing measurement routines
      that effectively reduce the noise floor, EMCD measurements can be pushed towards
      quantitative magnetic measurements even on individual nanoparticles. With this
      approach, the ratio of orbital to spin magnetic moments for the Fe atoms in a
      single L10 ordered FePt nanoparticle is determined to be ml/ms=0.08+/-0.02. This
      finding is in good quantitative agreement with the results of XMCD ensemble
      measurements.

PMID- 27694037
TI  - Fabrication of scanning thermal microscope probe with ultra-thin oxide tip and
      demonstration of its enhanced performance.
AB  - With the vigorous development of new nanodevices and nanomaterials, improvements
      in the quantitation and resolution of the measurement of nanoscale energy
      transport/conversion phenomena have become increasingly important. Although
      several new advanced methods for scanning thermal microscopy (SThM) have been
      developed to meet these needs, such methods require a drastic enhancement of SThM
      probe performance. In this study, by taking advantage of the characteristics of
      micromechanical structures where their mechanical stability is maintained even
      when the film that composes the structures becomes extremely thin, we develop a
      new design of SThM probe whose tip is made of ultra-thin SiO2 film (~100nm),
      fabricate the SThM probes, and demonstrate experimentally that the tip radius,
      thermal time constant, and thermal sensitivity of the probe are all improved. We
      expect the development of new high-performance SThM probes, along with the
      advanced measurement methods, to allow the measurement of temperature and thermal
      properties with higher spatial resolution and quantitative accuracy, ultimately
      making essential contributions to diverse areas of science and engineering
      related to the nanoscale energy transport/conversion phenomena.

PMID- 27694038
TI  - Targeting mast cells: Uncovering prolific therapeutic role in myriad diseases.
AB  - The mast cells are integral part of immune system and they have pleiotropic
      physiological functions in our body. Any type of abnormal stimuli causes the mast
      cells receptors to spur the otherwise innocuous mast cells to degranulate and
      release inflammatory mediators like histamine, cytokines, chemokines and
      prostaglandins. These mediators are involved in various diseases like allergy,
      asthma, mastocytosis, cardiovascular disorders, etc. Herein, we describe the
      receptors involved in degranulation of mast cells and are broadly divided into
      four categories: G-protein coupled receptors, ligand gated ion channels,
      immunoreceptors and pattern recognition receptors. Although, activation of
      pattern recognition receptors do not cause mast cell degranulation, but result in
      cytokines production. Degranulation itself is a complex process involving cascade
      of events like membrane fusion events and various proteins like VAMP, Syntaxins,
      DOCK5, SNAP-23, MARCKS. Furthermore, we described these mast cell receptors
      antagonists or agonists useful in treatment of myriad diseases. Like, omalizumab
      anti-IgE antibody is highly effective in asthma, allergic disorders treatment and
      recently mechanistic insight of IgE uncovered; matrix mettaloprotease inhibitor
      marimistat is under phase III trial for inflammation, muscular dystrophy
      diseases; ZPL-389 (H4 receptor antagonist) is in Phase 2a Clinical Trial for
      atopic dermatitis and psoriasis; JNJ3851868 an oral H4 receptor antagonist is in
      phase II clinical development for asthma, rheumatoid arthritis. Therefore,
      research is still in inchoate stage to uncover mast cell biology, mast cell
      receptors, their therapeutic role in myriad diseases.

PMID- 27694039
TI  - The effects of konjac oligosaccharide on TNBS-induced colitis in rats.
AB  - The purpose of the study was to assess the effects and the protective mechanism
      of konjac oligosaccharide (KOS) on the ulcerative colitis (UC) model induced by
      2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. KOS (1.0 and 4.0g/kg/day) was
      administered for 14days after the induction of colitis with TNBS. The status of
      the rats was assessed by morphological and biochemical methods. The effect of KOS
      on the colonic microflora was also assessed by studying the bacteria profile and
      short chain fatty acids (SCFAs) production in feces by standard culture
      techniques and gas chromatography, respectively. KOS administration improved rat
      weight, colonic length, damage score, structure of gut microbiota, production of
      SCFA, and reduced colon tissue levels of malondialdehyde (MDA), inducible nitric
      oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF
      alpha), and interleukin-1beta (IL-1beta). Therefore, our results indicate that
      KOS is an anti-inflammatory and could be useful as a prebiotic to design
      functional foods for UC.

PMID- 27694041
TI  - Investigating ego modules involved in TGFbeta3-induced chondrogenesis in
      mesenchymal stem cells based on ego network.
AB  - OBJECTIVE: This paper aimed to investigate ego modules for TGFbeta3-induced
      chondrogenesis in mesenchymal stem cells (MSCs) using ego network algorithm.
      METHODS: The ego network algorithm comprised three parts, extracting differential
      expression network (DEN) based on gene expression data and protein-protein
      interaction (PPI) data; exploring ego genes by reweighting DEN; and searching ego
      modules by ego gene expansions. Subsequently, permutation test was carried out to
      evaluate the statistical significance of the ego modules. Finally, pathway
      enrichment analysis was conducted to investigate ego pathways enriched by the ego
      modules. RESULTS: A total of 15 ego genes were obtained from the DEN, such as
      PSMA4, HNRNPM and WDR77. Starting with each ego genes, 15 candidate modules were
      gained. When setting the thresholds of the area under the receiver operating
      characteristics curve (AUC) >=0.9 and gene size >=4, three ego modules (Module 3,
      Module 8 and Module 14) were identified, and all of them had statistical
      significances between normal and TGFbeta3-induced chondrogenesis in MSCs. By
      mapping module genes to confirmed pathway database, their ego pathways were
      detected, Cdc20:Phospho-APC/C mediated degradation of Cyclin A for Module 3,
      Mitotic G1-G1/S phases for Module 8, and mRNA Splicing for Module 14.
      CONCLUSIONS: We have successfully identified three ego modules, evaluated their
      statistical significances and investigated their functional enriched ego
      pathways. The findings might provide potential biomarkers and give great insights
      to reveal molecular mechanism underlying this process.

PMID- 27694040
TI  - LOX-1 and TLR4 affect each other and regulate the generation of ROS in A.
      fumigatus keratitis.
AB  - PURPOSE: To explore the relationship between LOX-1 and TLR4 in Aspergillus
      fumigatus (A. fumigatus) keratitis. To determine LOX-1 and TLR4 can affect each
      other and regulate inflammation through regulation of the generation of reactive
      oxygen species (ROS) in A. fumigatus keratitis. METHODS: The cornea and abdominal
      cavity extracted neutrophils of susceptible C57BL/6 mice were infected with A.
      fumigatus. The cornea and neutrophils were pretreated with LOX-1 neutralizing
      antibody, Polyinosinic acid (Poly(I)) (the inhibitor of LOX-1) or CLI-095 (the
      inhibitor of TLR4) separately before infection. LOX-1, TLR4 and IL-1beta
      expression were detected in normal and infected cornea by PCR and Western Blot,
      while ROS was detected in the neutrophils by flow cytometry. RESULTS: LOX-1,
      TLR4, IL-1beta mRNA and protein levels were up-regulated in C57BL/6 cornea after
      infection. LOX-1 neutralizing antibody or Poly(I) pretreatment decreased the
      expression of LOX-1, TLR4 and IL-1beta in C57BL/6 cornea after infection and CLI
      095 pretreatment decreased the expression of LOX-1, TLR4 and IL-1beta in C57BL/6
      cornea after infection. ROS generation was increased in C57BL/6 neutrophils after
      infection, however, ROS generation was decreased in C57BL/6 neutrophils after
      infection by LOX-1 neutralizing antibody or Poly(I) or CLI-095 pretreatment.
      CONCLUSION: LOX-1, TLR4 and IL-1beta expression and ROS generation are increased
      after infection. LOX-1 and TLR4 can affect each other and regulate the generation
      of ROS in A. fumigatus keratitis. Inhibition of LOX-1 and TLR4 can reduce ROS
      generation.

PMID- 27694042
TI  - How effective is greening policy in reducing GHG emissions from agriculture?
      Evidence from Italy.
AB  - Agriculture contributes significantly to greenhouse gas (GHG) emissions,
      accounting for more than 10% of total CO2 emissions in the EU-28 area. The Common
      Agricultural Policy (CAP) plays an important role in promoting environmentally
      and climate friendly practices and needs to respond to the new environmental
      challenges by better integrating its objectives with other EU policies. In this
      respect, the recent CAP reform 2014-2020 made a further step, making a large part
      of direct payments conditional on new agricultural practices beneficial for the
      climate and the environment, i.e. "greening". In this study we estimate the
      potential environmental benefits from greening in terms of GHG emissions in four
      regions of Northern Italy, one of the major European agricultural areas in terms
      of emissions. The emissions were quantified and broken down into the three main
      GHGs (carbon dioxide, methane and nitrous oxide) per production process. This
      information was subsequently used in a Positive Mathematical Programming (PMP)
      farm-based model on more than 3,000 farms, to estimate the effects of greening on
      regional land use and its contribution in reducing the total emissions. The new
      agri-environmental constraints produce a modest abatement of total emissions of
      greenhouse gases (-1.5%) in the analyzed area. The model estimates a reduction in
      CO2 emissions of about 2%. Emissions from nitrous oxide show a decrease of 2.1%
      and the reduction in the methane is about 0.4% compared to the observed scenario.
      The process of "lightening" that affected the greening during the CAP negotiation
      has inevitably resulted in missing an opportunity to introduce a significant
      positive change of behaviour into agriculture, in line with the expectations and
      needs of society for EU agriculture as a provider of public goods.

PMID- 27694043
TI  - Wastewater sludge dewaterability enhancement using hydroxyl aluminum
      conditioning: Role of aluminum speciation.
AB  - Chemical conditioning is one of the most important processes for improve the
      performance of sludge dewatering device. Aluminum salt coagulant has been widely
      used in wastewater and sludge treatment. It is generally accepted that pre-formed
      speciation of aluminum salt coagulants (ASC) has an important influence on
      coagulation/flocculation performance. In this study, the interaction mechanisms
      between sludge particles and aluminum salt coagulants with different speciation
      of hydroxy aluminum were investigated by characterizing the changes in
      morphological and EPS properties. It was found that middle polymer state aluminum
      (Alb) and high polymer state aluminum (Alc) performed better than monomer
      aluminum and oligomeric state aluminum (Ala) in reduction of specific resistance
      to filtration (SRF) and compressibility of wastewater sludge due to their higher
      charge neutralization and formed more compact flocs. Sludge was significantly
      acidified after addition Ala, while pH was much more stable under Alb and Alc
      conditioning due to their hydrolysis stability. The size of sludge flocs
      conditioned with Alb and Alc was small but flocs structure was denser and more
      compact, and floc strength is higher, while that formed from Ala is relatively
      large, but floc structure was loose, floc strength is relatively lower. Scanning
      environmental microscope analysis revealed that sludge flocs conditioned by Alb
      and Alc (especially PAC2.5 and Al13) exhibited obvious botryoidal structure, this
      is because sludge flocs formed by Alb and Alc were more compact and floc strength
      is high, it was easy generated plentiful tiny channels for water release. In
      addition, polymeric aluminum salt coagulant (Alb, Alc) had better performance in
      compressing extracellular polymeric substances (EPS) structure and removing
      sticky protein-like substances from soluble EPS fraction, contributing to
      improvement of sludge filtration performance. Therefore, this study provides a
      novel solution for improving sludge dewatering property by controlling aluminum
      speciation.

PMID- 27694044
TI  - Physical activity, black carbon exposure and airway inflammation in an urban
      adolescent cohort.
AB  - OBJECTIVE: Regular physical activity can improve cardiopulmonary health; however,
      increased respiratory rates and tidal volumes during activity may increase the
      effective internal dose of air pollution exposure. Our objective was to
      investigate the impact of black carbon (BC) measured by personal sampler on the
      relationship between physical activity and fractional exhaled nitric oxide
      (FeNO), a marker of airway inflammation. We hypothesized that higher personal BC
      would attenuate the protective effect of physical activity on airway
      inflammation. METHODS: We performed a cross-sectional study nested in a birth
      cohort of African American and Dominican children living in the Bronx and
      Northern Manhattan, New York City. Children were recruited based on age (target 9
      14 year olds) and presence (n=70) or absence (n=59) of current asthma. Children
      wore wrist mounted accelerometers for 6 days and were classified as 'active' if
      they had >=60min of moderate-to-vigorous activity (MVA) each day and 'non-active'
      if they had <60min of MVA on any given day, based on CDC guidelines. Personal BC
      measured using a MicroAeth, was assessed during two 24-h periods, at the
      beginning and end of physical activity assessment. High BC was defined as the
      upper tertile of BC measured with personal sampler. FeNO measurements were
      sampled at the beginning and end of the of physical activity assessment. RESULTS:
      In multivariable linear regression models, 'active' children had 25% higher
      personal BC concentrations (p=0.02) and 20% lower FeNO (p=0.04) compared to 'non
      active' children. Among children with high personal BC (n=33), there was no
      relationship between activity and FeNO (p=1.00). The significant protective
      relationship between activity and airway inflammation was largely driven by
      children with lower personal BC (n=96, p=0.04). CONCLUSIONS: Children that live
      in an urban environment and are physically active on a daily basis have higher
      personal exposure to BC. High BC offsets the protective relationship between
      physical activity and airway inflammation.

PMID- 27694046
TI  - Linking toxicity profiles to pollutants in sludge and sediments.
AB  - Obtaining a complex picture of how pollutants synergistically influence toxicity
      of a system requires statistical correlation of chemical and ecotoxicological
      data. In this study, we determined concentrations of eight potentially toxic
      metals (PTMs) and four groups of organic pollutants in 15 sewage sludge and 12
      river sediment samples, then linked measured contaminant concentrations to the
      toxicity of each matrix through constrained correspondence analysis (CCA). In
      sludge samples, Hg, As, hexachlorohexane (HCH), polybrominated diphenyl ethers
      (PBDEs) and hexabromocyclododecane (HBCD) influenced the toxicity profiles, with
      the first four having significant effects and HBCD being marginally significant.
      In sediment samples, Hg, As, PBDEs, hexachlorobenzene (HCB),
      dichlorodiphenyltrichloroethane (DDT), HBCD, HCH and polycyclic aromatic
      hydrocarbons (PAHs) were found to explain toxicity profiles with Hg, As, PBDEs,
      HCB, DDT, HBCD, and HCH having significant effects and PAHs being marginally
      significant. Interestingly, HCH was present in small amounts yet proved to have a
      significant impact on toxicity. To the contrary, PAHs were often present in high
      amounts, yet proved to be only marginally significant for sediment toxicity.
      These results indicate that statistical correlation of chemical and
      ecotoxicological data can provide more detailed understanding of the role played
      by specific pollutants in shaping toxicity of sludge and sediments.

PMID- 27694045
TI  - Dietary selenium disrupts hepatic triglyceride stores and transcriptional
      networks associated with growth and Notch signaling in juvenile rainbow trout.
AB  - Dietary Se has been shown to adversely affect adult fish by altering growth rates
      and metabolism. To determine the underlying mechanisms associated with these
      observations, we measured biochemical and transcriptomic endpoints in rainbow
      trout following dietary Se exposures. Treatment groups of juvenile rainbow trout
      were fed either control Lumbriculus variegatus worms or worms cultured on
      selenized yeast. Selenized yeast was cultured at four nominal doses of 5, 10, 20
      or 40mg/kg Se dry weight (measured dose in the worms of 7.1, 10.7, 19.5, and
      31.8mg/kgSedw respectively) and fish were fed for 60days. At 60 d, hepatic
      triglycerides, glycogen, total glutathione, 8-isoprostane and the transcriptome
      response in the liver (n=8/group) were measured. Fish fed the nominal dose of 20
      and 40mg/kg Se dry weight had lower body weight and a shorter length, as well as
      lower triglyceride in the liver compared to controls. Evidence was lacking for an
      oxidative stress response and there was no change in total glutathione, 8
      isoprostane levels, nor relative mRNA levels for glutathione peroxidase isoforms
      among groups. Microarray analysis revealed that molecular networks for long-chain
      fatty acid transport, lipid transport, and low density lipid oxidation were
      increased in the liver of fish fed 40mg/kg, and this is hypothesized to be
      associated with the lower triglyceride levels in these fish. In addition, up
      regulated gene networks in the liver of 40mg/kg Se treated fish included
      epidermal growth factor receptor signaling, growth hormone receptor, and insulin
      growth factor receptor 1 signaling pathways. These molecular changes are
      hypothesized to be compensatory and related to impaired growth. A gene network
      related to Notch signaling, which is involved in cell-cell communication and gene
      transcription regulation, was also increased in the liver following dietary
      treatments with both 20 and 40mg/kg Se. Transcriptomic data support the
      hypothesis that dietary Se increases the expression of networks for growth
      related signaling cascades in addition to those related to fatty acid synthesis
      and metabolism. We propose that the disruption of metabolites related to
      triglyceride processing and storage, as well as gene networks for epidermal
      growth factor and Notch signaling in the liver, represent key molecular
      initiating events for adverse outcomes related to growth and Se toxicity in fish.

PMID- 27694047
TI  - Degradation mechanisms of DDX induced by the addition of toluene and glycerol as
      cosubstrates in a zero-valent iron pretreated soil.
AB  - Abiotic and biotic processes can be used to remediate DDX (DDT, DDD, DDE, and
      DDNS) contaminated soils; these processes can be fostered using specific carbon
      amendments to stimulate particular soil indigenous microbial communities to
      improve rates or extent of degradation. In this study, toluene and glycerol were
      evaluated as cosubstrates under aerobic and anoxic conditions to determine the
      degradation efficiencies of DDX and to elucidate possible degradation mechanisms.
      Slurry microcosms experiments were performed during 60 days using pretreated soil
      with zero-valent iron (ZVI). Toluene addition enhanced the percentage of
      degradation of DDX. DDNS was the main compound degraded (around 86%) under
      aerobic conditions, suggesting cometabolic degradation of DDX by toluene
      degrading soil bacteria. Glycerol addition under anoxic conditions favored the
      abiotic degradation of DDX mediated by sulfate-reducing bacteria activity, where
      DDT was the main compound degraded (around 90%). The 16S rDNA metagenomic
      analyses revealed Rhodococcus ruber and Desulfosporosinus auripigmenti as the
      predominant bacterial species after 40 days of treatment with toluene and
      glycerol additions, respectively. This study provides evidence of biotic and
      abiotic DDX degradation by the addition of toluene and glycerol as cosubstrates
      in ZVI pretreated DDX-contaminated soil.

PMID- 27694048
TI  - Gallic acid grafting modulates the oxidative potential of ferrimagnetic bioactive
      glass-ceramic SC-45.
AB  - Magnetite-containing glass-ceramics are promising bio-materials for replacing
      bone tissue after tumour resection. Thanks to their ferrimagnetic properties,
      they generate heat when subjected to an alternated magnetic field. In virtue of
      this they can be employed for the hyperthermic treatment of cancer. Moreover,
      grafting anti-cancer drugs onto their surface produces specific anti-neoplastic
      activity in these biomaterials. Gallic acid (GA) exhibits antiproliferative
      activity which renders it a promising candidate for anticancer applications. In
      the present paper, the reactivity of ferrimagnetic glass-ceramic SC-45 grafted
      with GA (SC-45+GA) was studied in terms of ROS release, rupture of the C-H bond
      of the formate molecule and Fenton reactivity by EPR/spin trapping in acellular
      systems. The ability of these materials to cause lipid peroxidation was assessed
      by UV-vis/TBA assay employing linoleic acid as a model of membrane lipid. The
      results, compared to those obtained with SC-45, showed that GA grafting (i)
      significantly enhanced the Fenton reactivity and (ii) restored the former
      reactivity of SC-45 towards both the C-H bond and linoleic acid which had been
      completely suppressed by prolonged contact with water. Fe2+ centres at the
      surface are probably implicated. GA, acting as a pro-oxidant, reduces Fe3+ to
      Fe2+ by maintaining a supply of Fe2+ at the surface of SC-45+GA.

PMID- 27694050
TI  - Biopolymeric hydrogels - nanostructured TiO2 hybrid materials as potential
      injectable scaffolds for bone regeneration.
AB  - The present work aims at development of novel hybrid materials from genipin
      crosslinked collagen or collagen/chitosan hydrogels containing various types of
      TiO2 nanoparticles characterized with different anatase/rutile ratios. Collagen
      and chitosan were selected as hydrogel components since they are biopolymers
      being, like collagen, the major compound present in extracellular matrix or
      exhibit structural similarity to glycosaminoglycans, like chitosan. TiO2
      nanoparticles were introduced to the hydrogel matrices to improve their
      mechanical properties as well as bioactivity. A series of twelve novel hybrid
      materials were prepared and their physicochemical, mechanical and biological
      properties were evaluated. It was found that TiO2 nanostructures introduced to
      the hydrogels have significant influence on the swelling properties of the
      synthesized hybrids and their impact is strongly dependent on the type of
      matrices. The surfaces of hybrid materials were found to be more hydrophilic than
      these of corresponding hydrogel matrix. It was also observed that, the storage
      modulus values of the hybrids based on collagen-chitosan hydrogel are comparable
      to these for plain hydrogels what indicates that the mechanical properties of the
      materials obtained are satisfactory for possible biomedical application. The in
      vitro cell culture studies have shown that prepared materials are biocompatible
      as they can support mitochondrial activity of MEFs as well as MG-63 cells. In
      vitro experiments performed under simulated body fluid (SBF) conditions have
      revealed that all studied TiO2 nanoparticles present in hydrogel matrices,
      regardless of anatase/rutile ratio, successfully induced formation of apatite
      like structures. The hybrid materials developed here are promising candidates for
      preparation of bioactive, injectable scaffolds for tissue engineering.

PMID- 27694049
TI  - Toxicity mechanism of titanium dioxide and zinc oxide nanoparticles against food
      pathogens.
AB  - Food preservation is an important field of research. It extends the shelf life of
      major food products. Our current study is based on food preservation through TiO2
      and ZnO nanoparticles. TiO2 and ZnO are biocompatible nanomaterial. The
      biocompatibility of the materials were established through toxicity studies on
      cell lines. Titanium dioxide and Zinc Oxide nanoparticle were synthesized by wet
      chemical process. They are characterized by X-Ray diffraction and TEM. The
      antibacterial activities of both the materials were analysed to ensure their
      effectiveness as food preservative against Salmonella typhi, Klebsiella
      pneumoniae and Shigella flexneri. The results indicates that TiO2 and ZnO
      nanoparticle inhibits Salmonella, Klebsiella and Shigella. The mode of action is
      by the generation of ROS in cases of Salmonella, Klebsiella. Mode of action in
      Shigella is still unclear. It was also proved that TiO2 and ZnO nanoparticle are
      biocompatible materials.

PMID- 27694051
TI  - Resveratrol induces chain interdigitation in DPPC cell membrane model systems.
AB  - Resveratrol is a natural polyphenol found in various plants with potential
      therapeutic activity as anti-oxidant, anti-inflammatory, cardioprotective and
      anti-tumoral. Lipid membranes are among cellular components that are targets of
      its action. In this work ESR of chain labeled lipids, calorimetry, X-ray
      diffraction and molecular docking are used to study the interaction of
      resveratrol with membrane model systems of dipalmitoylphosphatidylcholine (DPPC)
      as a function of resveratrol concentration (0-30 mol% of the lipid) and
      temperature (10-50 degrees C). Resveratrol incorporated in DPPC bilayers induces
      considerable motional restriction at the lipid tail termini, removing the
      gradient of increasing mobility along the chain found in DPPC bilayers in the gel
      phase. In contrast, it leaves unperturbed the DPPC chain flexibility profile in
      the liquid-crystalline phase. At low concentration, resveratrol progressively
      reduces the pre-transition temperature and eliminates the pre-transition for
      content >=5mol%. A reduced cooperativity and a downshift of the main transition
      temperature are observed, especially at high content. The typical diffraction
      pattern of DPPC multibilayers in the Lbeta' phase is converted to a lamellar
      pattern with reduced d-spacing of untilted lipid chain in a hexagonal packing at
      30 mol% of resveratrol. Molecular docking indicates that the energetically
      favoured anchoring site is the polar headgroup region, where resveratrol acts as
      a spacer. The overall results are consistent with the formation in DPPC of an
      interdigitated Lbetai gel phase induced by 30 mol% resveratrol.

PMID- 27694052
TI  - Influence of solution chemistry on the inactivation of particle-associated
      viruses by UV irradiation.
AB  - MS2 inactivation by UV irradiance was investigated with the focus on how the
      disinfection efficacy is influenced by bacteriophage MS2 aggregation and
      adsorption to particles in solutions with different compositions. Kaolinite and
      Microcystis aeruginosa were used as model inorganic and organic particles,
      respectively. In the absence of model particles, MS2 aggregates formed in either
      1mM NaCl at pH=3 or 50-200mM ionic strength CaCl2 solutions at pH=7 led to a
      decrease in the MS2 inactivation efficacy because the virions located inside the
      aggregate were protected from the UV irradiation. In the presence of kaolinite
      and Microcystis aeruginosa, MS2 adsorbed onto the particles in either 1mM NaCl at
      pH=3 or 50-200mM CaCl2 solutions at pH=7. In contrast to MS2 aggregates formed
      without the presence of particles, more MS2 virions adsorbed on these particles
      were exposed to UV irradiation to allow an increase in MS2 inactivation. In
      either 1mM NaCl at pH from 4 to 8 or 2-200mM NaCl solutions at pH=7, the absence
      of MS2 aggregation and adsorption onto the model particles explained why MS2
      inactivation was not influenced by pH, ionic strength, and the presence of model
      particles in these conditions. The influence of virus adsorption and aggregation
      on the UV disinfection efficiency found in this research suggests the necessity
      of accounting for particles and cation composition in virus inactivation for
      drinking water.

PMID- 27694055
TI  - Comparative assessment of cardiac activity and DNA damage in haemocytes of the
      Mediterranean mussel Mytilus galloprovincialis in exposure to tributyltin
      chloride.
AB  - This study gives an insight in sensitivity of heart rate (Hr) of Mytilus
      galloprovincialis as a physiological biomarker. Impact of tributyltin chloride
      (TBT-Cl) on Hr was studied in parallel with evaluation of mutagenic, genotoxic
      and cytotoxic potential of TBT-Cl (10, 100 and 1000MUg/L) within 96h treatment in
      static conditions. Mutagenic potential was assessed by SOS/umuC assay while
      genotoxicity was assessed in haemocytes of M. galloprovincialis by using the
      comet assay and the micronucleus test. Benzo(a)pyrene (B(a)P) was used as a
      positive control. Hr variations detected in TBT-Cl treatments can be linked to
      data obtained in the genotoxicological assays indicating that Hr can be
      considered and used as a reliable physiological biomarker for detecting the
      presence of organotin compounds. However despite the observed genotoxic potential
      of B(a)P, a noteworthy Hr response was not observed which further questions the
      potential of Hr in the detection of different types of pollutants.

PMID- 27694053
TI  - Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co
      glycolide particles loaded with an androstane-based cancer inhibitor.
AB  - In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with
      chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following
      their intravenous injection into mice. In this study we utilize an emulsification
      process and freeze drying to load the composite HAp/Ch-PLGA particles with 17beta
      hydroxy-17alpha-picolyl-androst-5-en-3beta-yl-acetate (A), a chemotherapeutic
      derivative of androstane and a novel compound with a selective anticancer
      activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the
      intact structure of the derivative A following its entrapment within HAp/Ch-PLGA
      particles. The thermogravimetric and differential thermal analyses coupled with
      mass spectrometry were used to assess the thermal degradation products and
      properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the
      comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA,
      equaled 7.47wt.%. The release of A from HAp/Ch-PLGA was sustained, neither
      exhibiting a burst release nor plateauing after three weeks. Atomic force
      microscopy and particle size distribution analyses were used to confirm that the
      particles were spherical with a uniform size distribution of d50=168nm. In vitro
      cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye
      exclusion assays demonstrated that the particles were cytotoxic to the A549 human
      lung carcinoma cell line (46+/-2%), while simultaneously preserving high
      viability (83+/-3%) of regular MRC5 human lung fibroblasts and causing no harm to
      primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA
      particles could be seen as promising drug delivery platforms for selective cancer
      therapies, targeting malignant cells for destruction, while having a
      significantly lesser cytotoxic effect on the healthy cells.

PMID- 27694054
TI  - The biological activity of cationic liposomes in drug delivery and toxicity test
      in animal models.
AB  - In the study we made use of DOTAP (1,2-dioleoyl-3-trimethylammonium), DOPE (1,2
      dioleoyl-snglycero-3-phosphoethanolamine) and PEG-PE (polyethylene glycol-
      polyethylene) to make cationic PEG-liposomes by ultrasonic dispersion method. The
      plasmid pGPU6 combined with cationic PEG-liposomes or Liopofectamin 2000 was used
      to transfect PC3 cells to judge the transfection efficiency. HE staining showed
      that the pGUP6-shAurora B plasmid/liposomes complex could significantly inhibit
      tumor growth in mice tumor model. The results indicated that there was no
      remarkable difference between the homemade liposomes and Lipofectamin 2000 after
      transfection, with transfection efficiency over 80%. And the homemade liposomes
      also had high transfection efficiency in vivo. No significant side effects were
      observed on weight, coat condition, behavior or appetite and the life span of
      mice treated with pGPU6-shAurora B were extended. Beyond that, there were no
      differences in mortality or in pathological changes to the heart, liver, spleen,
      lungs and kidneys among all the mice.

PMID- 27694056
TI  - Copper-64 labeled liposomes for imaging bone marrow.
AB  - INTRODUCTION: Bone marrow is the soft tissue compartment inside the bones made up
      of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells,
      and sinusoids. While [18F]-FLT has been utilized to image proliferative marrow,
      to date, there are no reports of particle based positron emission tomography
      (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled
      liposomal formulation that selectively targets bone marrow and therefore serves
      as an efficient PET probe for imaging bone marrow. METHODS: Optimized liposomal
      formulations were prepared with succinyl PE, DSPC, cholesterol, and mPEG-DSPE
      (69:39:1:10:0.1) with diameters of 90 and 140nm, and were doped with DOTA-Bn-DSPE
      for stable 64Cu incorporation into liposomes. RESULTS: PET imaging and
      biodistribution studies with 64Cu-labeled liposomes indicate that accumulation in
      bone marrow was as high as 15.18+/-3.69%ID/g for 90nm liposomes and 7.01+/
      0.92%ID/g for 140nm liposomes at 24h post-administration. In vivo biodistribution
      studies in tumor-bearing mice indicate that the uptake of 90nm particles is
      approximately 0.89+/-0.48%ID/g in tumor and 14.22+/-8.07%ID/g in bone marrow, but
      respective values for Doxil(r) like liposomes are 0.83+/-0.49%ID/g and 2.23+/
      1.00%ID/g. CONCLUSION: Our results indicate that our novel PET labeled liposomes
      target bone marrow with very high efficiency and therefore can function as
      efficient bone marrow imaging agents.

PMID- 27694057
TI  - Melanoma targeting with [99mTc(N)(PNP3)]-labeled alpha-melanocyte stimulating
      hormone peptide analogs: Effects of cyclization on the radiopharmaceutical
      properties.
AB  - The purpose of this study was to evaluate the effect of cyclization on the
      biological profile of a [99mTc(N)(PNP3)]-labeled alpha-melanocyte stimulating
      hormone peptide analog. A lactam bridge-cyclized H-Cys-Ahx-betaAla3-c[Lys4-Glu
      His-D-Phe-Arg-Trp-Glu10]-Arg11-Pro-Val-NH2 (NAP-NS2) and the corresponding linear
      H-Cys-Ahx-betaAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) peptide were
      synthetized, characterized by ESI-MS spectroscopy and their melanocortin-1
      receptor (MC1R) binding affinity was determined in B16/F10 melanoma cells. The
      consistent [99mTc(N)(PNP3)]-labeled compounds were readily obtained in high
      specific activity and their stability and biological properties were assessed. As
      an example, the chemical identity of [99mTc(N)(NAP-NS1)(PNP3)]+ was confirmed by
      carrier added experiments supported by radio/UV HPLC analysis combined with
      ESI(+)-MS. Compared with the linear peptide, cyclization negatively affected the
      biological properties of NAP-NS2 peptide by reducing its binding affinity for
      MC1R and by decreasing the overall excretion rate of the corresponding
      [99mTc(N)(PNP3)]-labeled peptide from the body as well as its in vivo stability.
      [99mTc(N)(NAP-NS1)(PNP3)]+ was evaluated for its potential as melanoma imaging
      probe in murine melanoma model. Data from in vitro and in vivo studies on B16/F10
      melanoma model of [99mTc(N)(NAP-NS1)(PNP3)]+ clearly evidenced that the
      radiolabeled linear peptide keeps its biological properties up on the conjugation
      to the [99mTc(N)(PNP3)]-building block. The progressive increase of the tumor-to
      nontarget ratios over the time indicates a quite stable interaction between the
      radio-complex and the MC1R.

PMID- 27694060
TI  - Dynamic gait stability of treadmill versus overground walking in young adults.
AB  - Treadmill has been broadly used in laboratory and rehabilitation settings for the
      purpose of facilitating human locomotion analysis and gait training. The
      objective of this study was to determine whether dynamic gait stability differs
      or resembles between the two walking conditions (overground vs. treadmill) among
      young adults. Fifty-four healthy young adults (age: 23.9+/-4.7years) participated
      in this study. Each participant completed five trials of overground walking
      followed by five trials of treadmill walking at a self-selected speed while their
      full body kinematics were gathered by a motion capture system. The spatiotemporal
      gait parameters and dynamic gait stability were compared between the two walking
      conditions. The results revealed that participants adopted a "cautious gait" on
      the treadmill compared with over ground in response to the possible inherent
      challenges to balance imposed by treadmill walking. The cautious gait, which was
      achieved by walking slower with a shorter step length, less backward leaning
      trunk, shortened single stance phase, prolonged double stance phase, and more
      flatfoot landing, ensures the comparable dynamic stability between the two
      walking conditions. This study could provide insightful information about dynamic
      gait stability control during treadmill ambulation in young adults.

PMID- 27694058
TI  - Monooxorhenium(V) complexes with 222-N2S2 MAMA ligands for bifunctional chelator
      agents: Syntheses and preliminary in vivo evaluation.
AB  - INTRODUCTION: Targeted radiotherapy using the bifunctional chelate approach with
      186/188Re(V) is challenging because of the susceptibility of monooxorhenium(V)
      based complexes to oxidize in vivo at high dilution. A monoamine-monoamide
      dithiol (MAMA)-based bifunctional chelating agent was evaluated with both rhenium
      and technetium to determine its utility for in vivo applications. METHODS: A 222
      MAMA chelator, 222-MAMA(N-6-Ahx-OEt) bifunctional chelator, and 222-MAMA(N-6-Ahx
      BBN(7-14)NH2) were synthesized, complexed with rhenium, radiolabeled with 99mTc
      and 186Re (carrier added and no carrier added), and evaluated in initial
      biological distribution studies. RESULTS: An IC50 value of 2.0+/-0.7nM for natReO
      222-MAMA(N-6-Ahx-BBN(7-14)NH2) compared to [125I]-Tyr4-BBN(NH2) was determined
      through competitive cell binding assays with PC-3 tumor cells. In vivo evaluation
      of the no-carrier added 99mTc-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed
      little gastric uptake and blockable pancreatic uptake in normal mice.
      CONCLUSIONS: The 186ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed stability
      in biological media, which indicates that the 222-N2S2 chelator is appropriate
      for chelating 186/188Re in radiopharmaceuticals involving peptides. Additionally,
      the in vitro cell studies showed that the ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2)
      complex (macroscopically) bound to PC3-tumor cell surface receptors with high
      affinity. The 99mTc analog was stable in vivo and exhibited pancreatic uptake in
      mice that was blockable, indicating BB2r targeting.

PMID- 27694059
TI  - Comparison of AUDIT-C collected via electronic medical record and self
      administered research survey in HIV infected and uninfected patients.
AB  - BACKGROUND: Using electronic medical record (EMR) data for clinical decisions,
      quality improvement, and research is common. While unhealthy alcohol use is
      particularly risky among HIV infected individuals (HIV+), the validity of EMR
      data for identifying unhealthy alcohol use among HIV+ is unclear. Among HIV+ and
      uninfected, we: (1) assess agreement of EMR and research AUDIT-C at validated
      cutoffs for unhealthy alcohol use; (2) explore EMR cutoffs that maximize
      agreement; and (3) assess subpopulation variation in agreement. METHODS: Using
      data from the Veterans Aging Cohort Study (VACS), EMR AUDIT-C cutoffs of 2+, 3+,
      and 4+ for men (2+ and 3+ for women) were compared to research AUDIT-C 4+ for men
      (3+ for women). Agreement was compared by demographics, HIV, hepatitis C
      infection, and alcohol related diagnosis. RESULTS: Among 1082 HIV+ and 1160
      uninfected men, 14% and 22% had an EMR and research AUDIT-C 4+, respectively.
      Among 32 HIV+ and 115 uninfected women, 9% and 14% had an EMR and research AUDIT
      C 3+. For men, EMR agreement with the research AUDIT-C 4+ was highest at a cutoff
      of 3+ (kappa=0.49). For women, EMR agreement with AUDIT-C 3+ was highest at a
      cutoff of 2+ (kappa=0.46). Moderate agreement was consistent across subgroups.
      CONCLUSIONS: EMR AUDIT-C underestimates unhealthy alcohol use compared to
      research AUDIT-C in both HIV+ and uninfected individuals. Methods for improving
      quality of clinical screening may be in need of investigation. Researchers and
      clinicians may consider alternative EMR cutoffs that maximize agreement given
      limitations of clinical screening.

PMID- 27694062
TI  - An unusual case of phakomatosis pigmentovascularis type IIb with Becker's nevus.

PMID- 27694061
TI  - Antibiofilm effect of warfarin on biofilm formation of Escherichia coli promoted
      by antimicrobial treatment.
AB  - Enhancement of microbial biofilm formation by low antimicrobial doses is a
      critical problem in the medical field. The objective of this study was to propose
      a new drug candidate against the biofilm formation promoted by subinhibitory dose
      of antimicrobials. To determine the effect on biofilm formation of Escherichia
      coli, a subinhibitory concentration of lactoferrin (LF), a milk protein involved
      in a broad range of biological properties including antimicrobial action, or
      ampicillin (AMP), a typical antibiotic, was added to an E. coli cell culture in a
      96-well microtiter plate. On the other hand, warfarin (WARF), an oral
      anticoagulant, or polymyxin B (PMB), a strong antibiotic for biofilm treatment,
      was added as an antagonist against the biofilm promoted by LF or AMP. The amount
      of biofilm formed at 100MUg/mL LF in lysogeny broth medium was four times higher
      than in the absence of LF. Meanwhile, it was found that WARF suppressed the LF
      promoted biofilm formation to a level comparable with the LF-free condition. WARF
      worked in a similar manner to PMB, which is known as an antibiofilm agent.
      Furthermore, WARF could also suppress the biofilm promoted by AMP. In conclusion,
      this study suggests that WARF can work as an antibiofilm agent against the
      biofilm formation promoted by subinhibitory dose of antimicrobials.

PMID- 27694063
TI  - Appropriate proton pump inhibitors use in elderly outpatients according to
      recommendations.
AB  - : Proton pump inhibitors (PPI) are widely prescribed, particularly in elderly
      patients, and their side effects are underestimated. Recommendations of the
      french health authorities, some specific to the elderly, specify their
      indications. The main objective of this descriptive and prospective study was to
      assess in elderly patients the adequacy of PPI prescriptions to these
      recommendations and to the marketing authorization. METHODS: Analysis of all
      patients hospitalized in an acute geriatric unit over a period of 2 years for
      which the drug prescription on admission included a PPI. RESULTS: For the 125
      patients included (mean age 84 years), the PPI treatment period exceeded one year
      in 68% of cases and 49.6% of PPI prescriptions were not consistent with the
      recommendations; not recommended indications are mainly prevention of
      gastroduodenal lesions in case of antiplatelet, VKA or corticosteroid treatment
      (24%), anemia (12%) or epigastric pain (8.5%) without prior endoscopic
      exploration. Only 50.4% of patients treated with PPI had an upper gastro
      intestinal endoscopy, which should be systematically performed in patients over
      65 years according to the recommendations. CONCLUSION: Our study confirms the low
      appropriateness of PPI prescriptions, particularly in elderly patients. This can
      be explained by controversial issues or by difficulties in adapting these
      recommendations in geriatric practice.

PMID- 27694064
TI  - Elderly and preventive care of the geriatric pathologies in African environment.
AB  - Senegal will not be spared by the process of the aging of its population. In
      fact, according to surveys, the demographic increase in the population of the old
      people, which is 3.5% higher than the national average (2.5%). But for the time
      being, gerontology problems are not arising in terms of demographic weight, but
      rather in terms of the breaking up of solidarity networks, uncontrolled
      urbanization and poverty. As far as health is concerned, the old people generally
      are faced with the same problems as their Northern counterparts; they are exposed
      to chronic diseases that demand their taking in charge in a long period of time.
      Besides, these diseases are a great handicap and they are also disabling
      diseases. So taking them in charge puts a financial on their meager family
      budgets or their pensions. In addition, there are no specialists in geriatrics,
      and those working in the field did not receive any training for that. Moreover,
      most of our health facilities are lacking in diagnostic means. Therefore,
      gerontology-geriatrics solutions that are adapted to our socio-economic context
      should be assigned straight away. The problem is not about stopping the process
      of aging, which, as a physiological process, is inevitable and irreversible, but
      rather delaying its effects. The matter at issue will be about how to set up a
      decentralized and integrated program that is designed to fight against geriatric
      diseases and disorders and that mainly focuses on screening and primary and
      secondary prevention, for our low financial resources and the low medical
      equipment of our health facilities cannot help us to adequately take charge of
      complications related to these diseases.

PMID- 27694065
TI  - A case of CD4+/CD8+ double-positive primary cutaneous anaplastic large cell
      lymphoma of the lip involving spontaneous regression after biopsy.

PMID- 27694067
TI  - Progressive Myoclonus Epilepsy: The Gene-Empowered Era.

PMID- 27694066
TI  - Angiokeratoma of the gluteal region in old age.

PMID- 27694068
TI  - Spontaneous resolution of cutaneous Langerhans cell histiocytosis in an infant.

PMID- 27694069
TI  - Mixed connective tissue disease with bilateral erythematous palpebral oedema and
      targetoid skin lesions.

PMID- 27694070
TI  - Migrant health: individual reflection and sentinel of the epidemiologic
      transition.

PMID- 27694071
TI  - Launch meeting of the French-speaking network for Neglected Tropical Diseases.

PMID- 27694072
TI  - Inter-regional medical cooperation in the Caribbean : a major asset for the
      influence of the French medicine.
AB  - Martinique was accepted as an associate member by the Council of Ministers of the
      Organization of Eastern Caribbean State since February 2015. This membership
      constitutes a major asset in bringing Martiniquais closer to the other Caribbean
      populations and should play a key role as it relates to regional cooperation
      especially in the domain of healthcare. Martinique and several Caribbean
      countries share common health issues such as; dengue, chikungunya virus, Zika
      Virus leptospirosis, snakebite, severe cardiovascular diseases (CVD), HTLV-1,
      sickle cell diseases and so on. This medical cooperation is mainly based in three
      important areas: training, teaching and transport (medical evacuations). The
      Inter-regional cooperation between the French Departments of the Americas and all
      other Caribbean countries is essential for the implementation and improvement of
      health care. It is urgent for the Caribbean professionals to discuss the
      possibilities of developing common solid relationships in training, collective
      scientific research, and continuous medical education.

PMID- 27694073
TI  - Peritonite a Pasteurella multocida.

PMID- 27694074
TI  - Diarrhees chez l'enfant.

PMID- 27694076
TI  - Frequence du typhus des broussailles.

PMID- 27694075
TI  - Plaies infectees et diabete.

PMID- 27694077
TI  - Melioidose severe.

PMID- 27694078
TI  - Tuberculose de l'enfant.

PMID- 27694079
TI  - Actualites.

PMID- 27694080
TI  - Cataracts in rural areas in Togo: awareness and attitudes.
AB  - To assess the prevalence of senile cataracts and the awareness and attitudes of
      patients with them in a rural area in Togo. We conducted a 10-weeks cross
      sectional ophthalmic screening in the prefecture of VO, 57 km from Lome, which
      sought to include individuals aged 50 years and older living in the study area.
      All patients underwent a comprehensive ophthalmic examination. Of the 3111
      patients expected, 767 came for the examination, for a participation rate of
      24.6%. The sex ratio was 0.8, and the patients' mean age was 60.1 +/- 8.7 years.
      The frequency of senile cataracts was 40.28%. Women had cataracts more often than
      men, with a sex ratio of 0.63. The frequency of unilateral blindness was 1.62%
      and 22% for bilateral blindness related to cataracts. Almost every participant
      (99.7%) knew the disease named cataract, but fewer than half (41.59%) knew its
      causes. Most patients (97.09%) accepted the idea of cataract surgery, but the
      lack of financial resources was a major barrier to it (64.72%). The frequency of
      senile cataracts is high in rural area. Decentralization of eye care is essential
      to give the right to sight to the population living in these areas.

PMID- 27694081
TI  - Tuberculosis in hemodialysis.
AB  - Chronic uremia puts patients at increased risk of infectious complications, in
      particular, tuberculosis. In this prospective study, we analyzed the clinical,
      paraclinical, and therapeutic features as well as outcome for all patients on
      chronic hemodialysis with tuberculosis from January 2010 through August 2012.
      Sixty-one patients were admitted for bacterial infections, 23% of them for
      tuberculosis. Fever was present in 71% of cases, and CRP elevated in all cases.
      The tuberculin skin test was positive in only 2 of 9 cases, and Mycobacterium
      tuberculosis isolated in 2 of 10 cases. Histological evidence was obtained in 7
      of 9 cases. Plain radiographs and computed tomography evoked tuberculosis. The
      location was extrapulmonary in 71% of cases. Chemotherapy for tuberculosis was
      based on a quadruple therapy for 10 patients and triple therapy for 3. The
      outcome was favorable in 11 patients and fatal for 3. Tuberculosis is much more
      common in hemodialysis patients than in the general population. The telltale
      signs are nonspecific. Prognosis is closely linked to early diagnosis and
      treatment.

PMID- 27694082
TI  - Prevalence of schistosomiasis and soil-transmitted helminth infections among
      schoolchildren in Burkina Faso.
AB  - To determine the current status of schistosomiasis and soil-transmitted helminth
      (STH) infections among schoolchildren after 10 years of mass treatment with
      praziquantel. Parasitological surveys were conducted in 2013 in 22 primary
      schools located in 11 regions of Burkina Faso. Urine filtration methods and Kato
      Katz techniques for stool were used to detect the eggs of Schistosoma
      haematobium, Schistosoma mansoni, and STH. 3514 schoolchildren aged from 7 to 11
      (1.415 +/- 9) years participated in the study. The prevalence of S. haematobium
      was 8.1% and of S. mansoni, 1.2%. The prevalence of intestinal schistosomiasis
      ranged from 0.6% to 26.2% and that of urinary schistosomiasis from 0.6% to 56.2%.
      The prevalence of hookworms was 1.1%, Ascaris lumbricoides 0.1%, and Trichuris
      trichiura 0.06%. The arithmetic mean of S. haematobium and S. mansoni were
      respectively 6 eggs/10 mL and 1.07 epg (eggs per gram). The arithmetic means of
      eggs were 0.07 epg, 0.03 epg, and 1.89 epg respectively for A. lumbricoides, T.
      trichiura, and Ankylostoma spp. This study shows the current situation for
      schistosomiasis and STH infections in different regions of Burkina Faso.
      Elimination of this parasitic disease requires the inclusion of other control
      methods, in addition to mass treatment.

PMID- 27694083
TI  - The relational dimension of care for maternity blues and its relation to
      decompensation of a psychiatric disorder during the intermediate postpartum
      period in Cameroon.
AB  - In a setting such as Cameroon, where perinatal care offers few services for women
      with psychiatric problems during pregnancy, delivery, and the immediate
      postpartum period, the development of the relational dimension of care may help
      prevent severe psychiatric disorders . This study evaluates the role of the
      relational dimension of perinatal and early postpartum care (providing perinatal
      counseling and a space to speak) on women with blues on the intermediate-term
      outcomes of decompensation, in view of the importance of the emotional issues
      occurring in the perinatal period. Data collection used both diagnostic and
      clinical methods on a sample of 50 women from three hospitals in Cameroon who
      gave birth during the study period and agreed to participate. Of the 38 diagnosed
      with blues, 10 were available for observation during the intermediate post
      partum: they were sorted into an experimental group that received perinatal
      counseling (n=5) and a control group that did not. The results suggest the
      importance to women with blues of a space for talking during the post-partum
      period. In particular, the quality of this counseling, in terms of the emotional
      responses of the nursing staff, determines the outcome of this management and can
      help to reduce the outset of depression and decompensation.

PMID- 27694084
TI  - Prevalence of Helicobacter pylori prevalence and upper gastrointestinal endoscopy
      in HIV/AIDS patients with gastrointestinal symptoms in the University Teaching
      Hospitals in Cameroon.
AB  - OBJECTIVE: To determine the prevalence of Helicobacter pylori (H. pylori)
      infection and of various upper gastrointestinal (GI) lesions in HIV+ patients
      with GI symptoms and the relation of H. pylori infection to CD4 cell counts.
      MATERIAL AND METHODS: In all, 56 HIV+ patients and 56 age- and sex-matched HIV-
      controls, all with upper GI symptoms, were evaluated by an upper endoscopy
      examination and gastric biopsy. H. pylori status was assessed with a urease test
      and histology. HIV was diagnosed with the rapid test and enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The prevalence of H. pylori was 50% (28/56
      [95%CI 36.3-63.7]) in HIV+ subjects and 55% (31/56 [95%CI 41.5-68.7]) in HIV-
      controls (p = 0.57). H. pylori infection rates did not differ significantly in
      HIV+ patients between those with a CD4 count >=200/mm3 (52%) and those with a CD4
      count <200/mm3 (42%) (p = 0.62). The prevalence on endoscopy of specific lesions
      in HIV+ patients and controls were compared: esophageal candidiasis (61%, 34/56
      vs. 7%; p<0.0001), esophageal ulcers (18%, 10/56 vs 2%; p = 0.01), corpus
      gastritis (41%; 23/56 vs 5%; p<0.0001), and duodenitis (20%, 11/56, vs 0%; p =
      0.001). CONCLUSIONS: The prevalence rate of H. pylori did not differ
      significantly between HIV+ and HIV- subjects. Prevalence of H. pylori was also
      lower, although not significantly, among HIV+ patients with CD4 T-cell counts
      below 200/mm3. On endoscopy, esophageal candidiasis was the most common finding
      in HIV+ patients, discovered by dysphagia.

PMID- 27694085
TI  - Inappropriate bradycardia in Ebola virus disease.
AB  - BACKGROUND: As part of French assistance for the outbreak of Ebola virus disease
      in west Africa, a military treatment center for infected healthcare workers was
      deployed in Conakry, Guinea. Although some cases of bradycardia have been
      reported since the first Ebola outbreak, they have never been documented to our
      knowledge. We studied heart rhythm in patients with Ebola virus disease to
      analyze inappropriate bradycardia and discuss its mechanism. METHODS: Nine
      patients who tested positive for Ebola were admitted in March 2015. Baseline
      clinical data were noted at admission and twice a day during follow-up, and
      laboratory analyses (with troponin testing) were performed. RESULTS: At
      admission, patients had no or moderate tachycardia (pulse = 82 +/- 27 bpm). Among
      them, a 32-year-old midwife admitted on her fourth day of symptoms had marked
      bradycardia: 43 bpm. ECG showed sinus bradycardia with no conduction disturbances
      or repolarization anomalies; findings were similar for the three other patients
      with bradycardia (< 60 bpm). During follow-up, her pulse gradually increased, as
      it did for the other three; all four recovered. DISCUSSION: Despite several
      factors likely to promote tachycardia, we observed no or only moderate
      tachycardia in all patients with Ebola. In our study, ECG recorded sinus rhythm,
      without significant node dysfunction or atrioventricular block. In the absence of
      any evidence of myocarditis, we discuss the possibility of a central nervous
      system cause, associated with encephalitis. CONCLUSION: We observed relative or
      marked bradycardia in our patients infected with Ebola. We hypothesize that its
      causal mechanism was encephalitis.

PMID- 27694086
TI  - Proper use of drugs and relation between purchasing power and cost of treatment
      prescribed in Casamance.
AB  - In Senegal, health insurance is available only to employees in the private and
      public sector and to the elderly (through the Sesame program). The rest of the
      population, especially different categories of vulnerable people, has no health
      insurance. Their access to healthcare and to medications is thus limited. In this
      study, we sought to analyze the relation between purchasing power and costs of
      treatment prescribed in one city. We questioned the customers leaving pharmacies
      in Ziguinchor, the administrative center of the lower Casamance, in southern
      Senegal, and analyzed their prescriptions and over-the-counter purchases. In all,
      we examined 255 prescriptions/purchases including 643 drugs; 29.4% were written
      by prescribers in the public health sector. The customers with these
      prescriptions were less educated, had lower incomes, used taxis more often, and
      consulted nurses more often than customers with prescriptions from the private
      health sector. Injectables and INN (international nonproprietary names) were
      dispensed most often to customers with prescriptions. Dispensing was usually
      better when the drug was prescribed, and when it was prescribed by a doctor.
      Nurses appeared to be inadequately trained in the proper use of medications. The
      percentage of drugs purchased did not depend on the patients' financial means or
      educational level. Those who most often acquired all of the drugs prescribed were
      those who had consulted a doctor rather than another type of healthcare provider.

PMID- 27694088
TI  - Detection of the serogoups and serotypes causing bacterial meningitidis in
      Bangui, 2012.
AB  - OBJECTIVE: The aim of this study was to identify the serogroup and serotypes
      causing bacterial meningitidis and to determine their prevalence in Bangui,
      Central African Republic. MATERIALS AND METHODS: Cerebrospinal fluid (CSF) from
      patients with suspected meningitis were collected and tested with cell counts,
      Gram staining, cultures, the latex agglutination test (LAT), and real-time PCR
      that used specific primers and probes for S. pneumoniae, N. meningitidis, and H.
      influenzae. Patients were eligible if they had a CSF sample as well as
      information about cell counts, Gram staining, the culture, the LAT, and the PCR.
      Antibiotic detection disks from Bio-Rad laboratory were used to test for the
      presence of antibiotic activity in the CSF. An uncorrected Chi2 test was used for
      comparisons. RESULTS: Of the 216 CSF samples collected, 71 were analyzed: 17 Gram
      stains were positive, as were 6 cultures, 15 LATs, and 33 PCRs. Among the latter,
      the serogroup distribution was highest for S. pneumoniae, which accounted for 82%
      (27/33) of the positive cases; H. influenzae type b accounted for 12% (4/33), and
      N. meningitidis A for 6% (2/33) positive cases. N. meningitidis No W135, N.
      meningitides B, N. meningitides X, or Streptococcus C serogroups were isolated.
      CONCLUSION: One year after the introduction of the PCV 13 vaccine, S. pneumoniae
      was identified as the predominant disease-causing strain. This study demonstrated
      the essential role of laboratory confirmation of meningitis cases to assess
      changes in disease epidemiology.

PMID- 27694087
TI  - Efficacy of sulfadoxine-pyrimethamine for the treatment of uncomplicated
      falciparum malaria in southern Mauritania.
AB  - BACKGROUND: Until 2006, the Mauritanian Ministry of Health recommended
      chloroquine and sulfadoxine-pyrimethamine for first- and second-line treatment of
      uncomplicated malaria, respectively. This study assessed the clinical efficacy of
      sulfadoxine-pyrimethamine in Kobeni as first-line treatment. MATERIALS AND
      METHODS: This study included 55 patients with Plasmodium falciparum infections,
      who were treated with sulfadoxine-pyrimethamine and followed up for 28 days.
      Isolates were genotyped to distinguish between recrudescence and reinfection.
      Treatment success rates and survival were analysed per protocol to evaluate drug
      efficacy. RESULTS: After inclusion, 2 patients were excluded for protocol
      violations, and 3 patients were lost to follow-up. Of the remaining 50 patients
      (per protocol population), 43 (86%) had adequate clinical and parasitological
      responses. Of the 7 patients with treatment failure, 5 (10%) were early failures,
      while 2 (4%) had initially responded and had late clinical failure on day 7,
      associated with recrudescence. With the exception of one adult weighing 91 kg,
      all treatment failures occurred in children aged from 7 to 12 years. CONCLUSIONS:
      Sulfadoxine-pyrimethamine monotherapy was moderately effective but insufficiently
      reliable in view of the relatively high rate of early treatment failure. The high
      prevalence of chloroquine resistance found in earlier studies and the results of
      the present study on sulfadoxine-pyrimethamine justify the change in national
      policy and systematic use of artemisinin-based combination therapy for first-line
      treatment of P. falciparum malaria in Mauritania.

PMID- 27694089
TI  - Therapeutic patient education and disclosure of status of HIV infected children
      in Yaounde, Cameroon Achievements and competence.
AB  - INTRODUCTION: Psychosocial support and therapeutic patient education are
      recommended practices that are poorly reported. Our objective was to describe the
      main achievements after a patient therapeutic education program conducted for pre
      adolescents and adolescents with HIV infection. METHOD: This qualitative study of
      37 children with a mean age of 11 years assessed the outcome of an educational
      program of 8 sessions that ended by the disclosure of their HIV status.
      Semistructured interviews that took place 8 weeks after the last session and
      lasted 20 minutes evaluated the following areas: knowledge of the disease, its
      treatment, its prevention, and their skills in managing their treatment and the
      secret. RESULTS: The level of knowledge was acceptable except about HIV
      transmission, and specifically, how they had acquired the disease. In all, 33/37
      (89%) of the children were able to cite or write the name of their disease; 29/37
      (78%) had acquired knowledge of their treatment (name of the drugs, objective,
      and daily treatment times); they were able to manage treatment intake away from
      home; and secrecy was the standard for all. However, many were unable to explain
      how they had acquired the virus. CONCLUSION: Therapeutic patient education for
      HIV status disclosure enables adolescents to acquire knowledge about their
      disease and the ability to manage it. The poor results observed for knowledge of
      transmission needs to be improved after disclosure in support groups.

PMID- 27694090
TI  - Malnutrition: prevalence and risk factors among the children younger than five
      years in a semi-urban area of Abidjan.
AB  - INTRODUCTION: In Cote d'Ivoire, the prevalence of malnutrition among children
      younger than 5 years exceeded 5% in 2011 and was thus considered serious. This
      overall prevalence may nonetheless mask differences and specificities between
      regions and municipalities. This study sought to determine the prevalence and
      risk factors of malnutrition among children in this age group in a semi-urban
      area of Abidjan. METHODS: This exhaustive, descriptive, cross-sectional survey
      took place from May 6 to July 31, 2010. The children's nutritional status was
      determined according to the WHO criteria. Univariate and multivariate analysis of
      factors associated with malnutrition (social and demographic characteristics,
      immunization status, children's eating practices, and household characteristics)
      were studied. RESULTS: We visited 668 households and recruited 809 children. The
      prevalence of malnutrition was 22.5%. Multivariate analysis showed that the
      introduction of porridge after 6 months halved the risk of malnutrition. Risk
      tripled for children whose father's occupation did not guarantee a regular
      income. CONCLUSION: Among the factors highlighted by this study, dietary
      practices seem the most amenable to corrective action. For example, the adoption
      of outreach programs by the Maternal and Child Protection services could improve
      nutritional practices in households.

PMID- 27694091
TI  - Tuberculosis in children in Togo: epidemiology, diagnosis, treatment, and
      outcome.
AB  - INTRODUCTION: Tuberculosis (TB) remains one of the most lethal communicable
      diseases in the world, according to the World Health Organization (WHO). New
      strategies must be implemented to meet targets for 2035. OBJECTIVE: Describe the
      epidemiological and therapeutic aspects of tuberculosis in children in Togo.
      MATERIALS AND METHODS: This retrospective, multicenter, descriptive cross
      sectional study examined the files of children younger than 15 years who were
      diagnosed with TB and treatment in the Maritime region from 2008 to 2011.
      RESULTS: The study included 74 children aged 0-15 years, for an average of 18
      cases of childhood tuberculosis annually. Pulmonary tuberculosis (38 cases) was
      the most common. TB-HIV co-infection was found in 14.9% of cases. Boys accounted
      for more than half of the patients. The age range of 11-15 years accounted for
      the highest proportion of cases (41.9%). The most common treatment was a
      combination of 2RHZE and 4RH (25 children, 33.8%). Laboratory monitoring was
      satisfactory. In all, 56 (75.7%) children were cured, and 14 (18.2%) lost to
      follow-up, while 3 (4%) died (all with TB/HIV). CONCLUSION: Active testing for
      HIV infection is essential in children with TB, because the combination of the
      two can be lethal.

PMID- 27694092
TI  - Tetanus in women of childbearing age in the infectious disease department in the
      national hospital of Conakry (Guinea).
AB  - OBJECTIVES: This study aimed to determine the hospital prevalence rate of tetanus
      in women of childbearing age in the infectious disease department of Donka CHU in
      Conakry and to describe their sociodemographic characteristics and outcomes.
      METHODOLOGY: This descriptive retrospective study examined the records of all
      patients aged 15 to 495 years hospitalized for tetanus over a 10-year period.
      RESULTS: During the study period, 74555 patients were hospitalized - 239 for
      tetanus. In all, 22 woman of childbearing age had tetanus, that is, 9.2%. Their
      mean age was 325 years. Most of the women were married (13/22) and lived in
      Conakry (18/22); 165 were housewives, and 65 patients had begun but not completed
      the required vaccinations. The incubation period was >75 days for 165 patients.
      Tetanus infection resulted from medical procedures for 9 women and trauma for 6.
      We recorded 125 deaths. The average duration of hospitalization was 215 days.
      CONCLUSION: Preventing tetanus requires a reinforcement of vaccination drives and
      especially the implementation of policies for booster reminders.

PMID- 27694093
TI  - Supply of care and neighborhood types in Libreville.
AB  - Libreville, capital of the Gabonese Republic takes, is part of the worldwide
      urban planning movement that has recently reached the emerging nations. In this
      context of increasing urbanization, the health coverage of the population is an
      important issue. We conducted a field study of the health facilities of all
      sectors to collect geographical coordinates to map them in 2014. Overall, we
      mapped 447 medical facilities. Then, in March 2014 we selected 300 households for
      an investigation in 3 districts (Nkembo, Nzeng Ayong, and Melen) of Libreville.
      The objective of the investigation was to collect the households' opinions about
      the geographical accessibility of these facilities. The results enabled us to map
      these facilities and showed a gradient. Assessment of the distance between these
      facilities according to district showed that the central district of Nkembo is
      closer to them than were the pericentral and peripheral neighborhoods. These
      results tend to show spatial disparities in the supply of health care. At the
      same time, the assessment of the geographical distance between these facilities
      and users' homes varies according to the type of district. These results raise
      the issue of urban planning and healthcare supply in Libreville.

PMID- 27694094
TI  - Epidemiological data and forensic aspects of road traffic fatalities in Lome,
      Togo.
AB  - We collected 190 forensic records from the only pathology laboratory in Lome,
      over the period from January 2010 to December 2014. The sex ratio (M/F) was 4.4
      and the decedents' average age 33.4 years. In 43.2% of cases, the accident
      resulted from a collision between a pedestrian and a motorcycle; excess speed
      noted in 56.8% of cases. Four principal groups of fatal injuries were observed:
      polytrauma (136 cases), isolated severe head injury (49 cases), isolated thoracic
      contusion (3 cases), and abdominal pelvic contusion with perinea trauma (2
      cases).

PMID- 27694095
TI  - Anterior uveitis as the first sign of human African trypanosomiasis: a case
      report.
AB  - We report the case of a 13-year-old girl who consulted for blurred vision, pain,
      and redness in her left eye. Ophthalmologic examination revealed chronic,
      hypertensive, and non-granulomatous anterior uveitis. The disease course was
      marked by a reversal of diurnal rhythm, with daytime sleepiness and behavioral
      disorders. A neuropsychiatric examination suggested human African trypanosomiasis
      (HAT), or sleeping sickness. The diagnosis was confirmed by the detection of
      Trypanosoma in the cerebrospinal fluid. The NECT regimen (nifurtimox-eflornithine
      combination therapy) was administered as medical treatment and resulted in the
      disappearance of all clinical signs. This observation suggests that the diagnosis
      of HAT can be considered in cases of anterior uveitis in individuals with a
      history of residence in or travel to an area endemic for it.

PMID- 27694096
TI  - Agminated Spitz nevus arising in normal skin with redundant HRAS mutation.

PMID- 27694097
TI  - Role of Large Clinical Datasets From Physiologic Monitors in Improving the Safety
      of Clinical Alarm Systems and Methodological Considerations: A Case From Philips
      Monitors.
AB  - BACKGROUND: Large datasets of the audit log of modern physiologic monitoring
      devices have rarely been used for predictive modeling, capturing unsafe
      practices, or guiding initiatives on alarm systems safety. OBJECTIVE: This paper
      (1) describes a large clinical dataset using the audit log of the physiologic
      monitors, (2) discusses benefits and challenges of using the audit log in
      identifying the most important alarm signals and improving the safety of clinical
      alarm systems, and (3) provides suggestions for presenting alarm data and
      improving the audit log of the physiologic monitors. METHODS: At a 20-bed
      transplant cardiac intensive care unit, alarm data recorded via the audit log of
      bedside monitors were retrieved from the server of the central station monitor.
      RESULTS: Benefits of the audit log are many. They include easily retrievable data
      at no cost, complete alarm records, easy capture of inconsistent and unsafe
      practices, and easy identification of bedside monitors missed from a unit change
      of alarm settings adjustments. Challenges in analyzing the audit log are related
      to the time-consuming processes of data cleaning and analysis, and limited
      storage and retrieval capabilities of the monitors. CONCLUSIONS: The audit log is
      a function of current capabilities of the physiologic monitoring systems,
      monitor's configuration, and alarm management practices by clinicians. Despite
      current challenges in data retrieval and analysis, large digitalized clinical
      datasets hold great promise in performance, safety, and quality improvement.
      Vendors, clinicians, researchers, and professional organizations should work
      closely to identify the most useful format and type of clinical data to expand
      medical devices' log capacity.

PMID- 27694098
TI  - Prediction of Sepsis in the Intensive Care Unit With Minimal Electronic Health
      Record Data: A Machine Learning Approach.
AB  - BACKGROUND: Sepsis is one of the leading causes of mortality in hospitalized
      patients. Despite this fact, a reliable means of predicting sepsis onset remains
      elusive. Early and accurate sepsis onset predictions could allow more aggressive
      and targeted therapy while maintaining antimicrobial stewardship. Existing
      detection methods suffer from low performance and often require time-consuming
      laboratory test results. OBJECTIVE: To study and validate a sepsis prediction
      method, InSight, for the new Sepsis-3 definitions in retrospective data, make
      predictions using a minimal set of variables from within the electronic health
      record data, compare the performance of this approach with existing scoring
      systems, and investigate the effects of data sparsity on InSight performance.
      METHODS: We apply InSight, a machine learning classification system that uses
      multivariable combinations of easily obtained patient data (vitals, peripheral
      capillary oxygen saturation, Glasgow Coma Score, and age), to predict sepsis
      using the retrospective Multiparameter Intelligent Monitoring in Intensive Care
      (MIMIC)-III dataset, restricted to intensive care unit (ICU) patients aged 15
      years or more. Following the Sepsis-3 definitions of the sepsis syndrome, we
      compare the classification performance of InSight versus quick sequential organ
      failure assessment (qSOFA), modified early warning score (MEWS), systemic
      inflammatory response syndrome (SIRS), simplified acute physiology score (SAPS)
      II, and sequential organ failure assessment (SOFA) to determine whether or not
      patients will become septic at a fixed period of time before onset. We also test
      the robustness of the InSight system to random deletion of individual input
      observations. RESULTS: In a test dataset with 11.3% sepsis prevalence, InSight
      produced superior classification performance compared with the alternative scores
      as measured by area under the receiver operating characteristic curves (AUROC)
      and area under precision-recall curves (APR). In detection of sepsis onset,
      InSight attains AUROC = 0.880 (SD 0.006) at onset time and APR = 0.595 (SD
      0.016), both of which are superior to the performance attained by SIRS (AUROC:
      0.609; APR: 0.160), qSOFA (AUROC: 0.772; APR: 0.277), and MEWS (AUROC: 0.803;
      APR: 0.327) computed concurrently, as well as SAPS II (AUROC: 0.700; APR: 0.225)
      and SOFA (AUROC: 0.725; APR: 0.284) computed at admission (P<.001 for all
      comparisons). Similar results are observed for 1-4 hours preceding sepsis onset.
      In experiments where approximately 60% of input data are deleted at random,
      InSight attains an AUROC of 0.781 (SD 0.013) and APR of 0.401 (SD 0.015) at
      sepsis onset time. Even with 60% of data missing, InSight remains superior to the
      corresponding SIRS scores (AUROC and APR, P<.001), qSOFA scores (P=.0095; P<.001)
      and superior to SOFA and SAPS II computed at admission (AUROC and APR, P<.001),
      where all of these comparison scores (except InSight) are computed without data
      deletion. CONCLUSIONS: Despite using little more than vitals, InSight is an
      effective tool for predicting sepsis onset and performs well even with randomly
      missing data.

PMID- 27694099
TI  - Metadata Correction of: How Best to Obtain Valid, Verifiable Data Online From
      Male Couples? Lessons Learned From an eHealth HIV Prevention Intervention for HIV
      Negative Male Couples.
AB  - [This corrects the article DOI: 10.2196/publichealth.6392.].

PMID- 27694101
TI  - Reducing missed appointments in a paediatric diabetes clinic: a successful
      endeavour.

PMID- 27694102
TI  - Change to Australasian College of Sport and Exercise Physicians-position
      statement: the place of mesenchymal stem/stromal cell therapies in sport and
      exercise medicine.

PMID- 27694103
TI  - Managing back pain and osteoarthritis without paracetamol: Physical treatments
      are the way forward.

PMID- 27694100
TI  - Electronic Quality of Life Assessment Using Computer-Adaptive Testing.
AB  - BACKGROUND: Quality of life (QoL) questionnaires are desirable for clinical
      practice but can be time-consuming to administer and interpret, making their
      widespread adoption difficult. OBJECTIVE: Our aim was to assess the performance
      of the World Health Organization Quality of Life (WHOQOL)-100 questionnaire as
      four item banks to facilitate adaptive testing using simulated computer adaptive
      tests (CATs) for physical, psychological, social, and environmental QoL. METHODS:
      We used data from the UK WHOQOL-100 questionnaire (N=320) to calibrate item banks
      using item response theory, which included psychometric assessments of
      differential item functioning, local dependency, unidimensionality, and
      reliability. We simulated CATs to assess the number of items administered before
      prespecified levels of reliability was met. RESULTS: The item banks (40 items)
      all displayed good model fit (P>.01) and were unidimensional (fewer than 5% of t
      tests significant), reliable (Person Separation Index>.70), and free from
      differential item functioning (no significant analysis of variance interaction)
      or local dependency (residual correlations < +.20). When matched for reliability,
      the item banks were between 45% and 75% shorter than paper-based WHOQOL measures.
      Across the four domains, a high standard of reliability (alpha>.90) could be
      gained with a median of 9 items. CONCLUSIONS: Using CAT, simulated assessments
      were as reliable as paper-based forms of the WHOQOL with a fraction of the number
      of items. These properties suggest that these item banks are suitable for
      computerized adaptive assessment. These item banks have the potential for
      international development using existing alternative language versions of the
      WHOQOL items.

PMID- 27694104
TI  - Regulatory effects of electronic beam irradiation on mir-21/smad7-mediated
      collagen I synthesis in keloid-derived fibroblasts.
AB  - Keloid scarring is an abnormal pathological scar characterized by excessive fibro
      proliferation and extracellular matrix deposition. Electronic beam irradiation is
      commonly used with surgical removal to control high recurrence rates of keloid
      scarring; however, the mechanism remains unknown. In this study, we used keloid
      derived primary fibroblasts (KF) as the cell model, and a dose of 15 Gy energy,
      followed by quantitative PCR (qPCR), western blotting and gene
      overexpression/knock down techniques were used to reveal the molecular mechanisms
      affected by electronic beam irradiation. We found that mir-21 was highly
      expressed in KF and was downregulated by irradiation. We also showed that smad7
      was a direct target of mir-21. Moreover, the expression level of smad7 was low in
      KF and upregulated by irradiation. We also found that smad7 controls Col-1
      synthesis by mediating p38 phosphorylation, and this process was affected by
      electronic beam irradiation. The regulatory effect of electronic beam irradiation
      on the expression of mir-21, smad7, p38, p-p38 and Col-1 could be partly restored
      by mir-21 overexpression achieved by mir-21 mimic transfection. In conclusion,
      our data demonstrated that mir-21/smad7 regulated Col-1 expression in KF and that
      electronic beam irradiation was capable of decreasing Col-1 production by
      modifying mir-21/smad7-mediated p38 activation. This is the first report
      identifying the effects of electronic beam irradiation on miRNAs, providing a
      novel strategy to discover the molecular mechanisms of radiotherapy.

PMID- 27694105
TI  - Establishment of a novel retinoblastoma (Rb) nude mouse model by intravitreal
      injection of human Rb Y79 cells - comparison of in vivo analysis versus
      histological follow up.
AB  - Retinoblastoma (Rb) is the most frequent primary intraocular tumour in children
      and, if left untreated, can cause death. Preclinical animal models that mimic
      molecular, genetic, and cellular features of cancers are essential for studying
      cancer and searching for promising diagnosis and treatment modalities. There are
      several models described for Rb, but none of them fully meet our requirements.
      The aim of this study was to create a novel xenograft-nude mouse-model with broad
      application possibilities, which closely resembles the clinical observations of
      Rb patients and which could be used to investigate the development and spread of
      the tumour by using scanning laser ophthalmoscopy/optical coherence tomography
      (SLO/OCT) as well as histology methods. We injected human retinoblastoma Y79
      cells intravitreally in both eyes of immune-deficient nude mice. The incidences
      of retinoblastoma as well as growth velocity were analysed 3, 6, 9 and 12 weeks
      after cell injection in vivo by SLO/OCT as well as ex vivo by electron microscopy
      (EM) and hematoxylin/eosin (HE) staining. Moreover, internal organs were
      histologically screened for potentially occurring metastases. Three weeks post
      injection, animals developed a retinoblastoma, and after five weeks tumour growth
      resulted in swelling of the eyes in individual animals, showing a similar
      phenotype to that of untreated Rb patients at advanced stages of tumour
      development. After 12 weeks, 67.5% of all analysed eyes (29 of 42) contained a
      retinoblastoma. At early stages of Rb development, the SLO/OCT analysis
      correlated with the histology results. If the tumours were too large, only
      histological investigations were feasible. The ultrastructural characteristics of
      the xenograft-tumours were very similar to those described for patient's tumours.
      In one mouse, brain metastases were observed. Our retinoblastoma mouse model
      closely resembles the human disease. SLO/OCT can be used for the detection of Rb
      at early stages of development and could be used for monitoring the success of
      future therapies.

PMID- 27694106
TI  - Oviposition preferences for ethanol depend on spatial arrangement and differ
      dramatically among closely related Drosophila species.
AB  - Recent work on the model fly Drosophila melanogaster has reported inconsistencies
      in their preference for laying eggs on intermediate concentrations of ethanol. In
      this study, we resolve this discrepancy by showing that this species strongly
      prefers ovipositing on ethanol when it is close to a non-ethanol substrate, but
      strongly avoids ethanol when options are farther apart. We also show fluidity of
      these behaviors among other Drosophila species: D. melanogaster is more
      responsive to ethanol than close relatives in that it prefers ethanol more than
      other species in the close-proximity case, but avoids ethanol more than other
      species in the distant case. In the close-proximity scenario, the more ethanol
      tolerant species generally prefer ethanol more, with the exception of the island
      endemic D. santomea This species has the lowest tolerance in the clade, but
      behaves like D. melanogaster We speculate that this could be an adaptation to
      protect eggs from parasites or predators such as parasitoid wasps, as larvae
      migrate to non-toxic substrates after hatching. These natural differences among
      species are an excellent opportunity to study how genes and brains evolve to
      alter ethanol preferences, and provide an interesting model for genetic variation
      in preferences in other organisms, including humans.

PMID- 27694108
TI  - The Burden of Cancer in Asian Americans: A Report of National Mortality Trends by
      Asian Ethnicity.
AB  - BACKGROUND: Asian Americans (AA) are the fastest growing U.S. population, and
      when properly distinguished by their ethnic origins, exhibit substantial
      heterogeneity in socioeconomic status, health behaviors, and health outcomes.
      Cancer is the second leading cause of death in the United States, yet trends and
      current patterns in the mortality burden of cancer among AA ethnic groups have
      not been documented. METHODS: We report age-adjusted rates, standardized
      mortality ratios, and modeled trends in cancer-related mortality in the following
      AA ethnicities: Asian Indians, Chinese, Filipinos, Japanese, Koreans, and
      Vietnamese, from 2003 to 2011, with non-Hispanic whites (NHW) as the reference
      population. RESULTS: For most cancer sites, AAs had lower cancer mortality than
      NHWs; however, mortality patterns were heterogeneous across AA ethnicities.
      Stomach and liver cancer mortality was very high, particularly among Chinese,
      Koreans, and Vietnamese, for whom these two cancer types combined accounted for
      15% to 25% of cancer deaths, but less than 5% of cancer deaths in NHWs. In AA
      women, lung cancer was a leading cause of death, but (unlike males and NHW
      females) rates did not decline over the study period. CONCLUSIONS: Ethnicity
      specific analyses are critical to understanding the national burden of cancer
      among the heterogeneous AA population. IMPACT: Our findings highlight the need
      for disaggregated reporting of cancer statistics in AAs and warrant consideration
      of tailored screening programs for liver and gastric cancers. Cancer Epidemiol
      Biomarkers Prev; 25(10); 1371-82. (c)2016 AACR.

PMID- 27694109
TI  - Messages to Motivate Human Papillomavirus Vaccination: National Studies of
      Parents and Physicians.
AB  - BACKGROUND: Physician communication about human papillomavirus (HPV) vaccine is a
      key determinant of uptake. To support physician communication, we sought to
      identify messages that would motivate HPV vaccination. METHODS: From 2014 to
      2015, we surveyed national samples of parents of adolescents ages 11 to 17 (n =
      1,504) and primary care physicians (n = 776). Parents read motivational messages,
      selected from nine longer messages developed by the Centers for Disease Control
      and Prevention and six brief messages developed by the study team. Parents
      indicated whether each message would persuade them to get HPV vaccine for their
      adolescents. Physicians read the brief messages and indicated whether they would
      use them to persuade parents to get HPV vaccine for 11- to 12-year-old children.
      RESULTS: The highest proportion of parents (65%) and physicians (69%) found this
      brief message to be persuasive: "I strongly believe in the importance of this
      cancer-preventing vaccine for [child's name]." Parents disinclined to vaccinate
      were most receptive to messages with information about HPV infection being
      common, cancers caused by HPV, and HPV vaccine effectiveness. Parents'
      endorsement did not vary by race/ethnicity, education, child age, or child sex
      (all P > 0.05). CONCLUSIONS: Our national surveys of parents and physicians
      identified messages that could motivate HPV vaccination, even among parents
      disinclined to vaccinate their children. The lack of difference across
      demographic subgroups in parental endorsement may suggest that these messages can
      be used across these subgroups. IMPACT: Our findings support physicians' use of
      these messages with parents to help motivate uptake of this important cancer
      preventing vaccine. Cancer Epidemiol Biomarkers Prev; 25(10); 1383-91. (c)2016
      AACR.

PMID- 27694110
TI  - Left ventricular shape predicts different types of cardiovascular events in the
      general population.
AB  - OBJECTIVE: To investigate whether sphericity volume index (SVI), an indicator of
      left ventricular (LV) remodelling, predicts incident cardiovascular events
      (coronary heart disease, CHD; all cardiovascular disease, CVD; heart failure, HF;
      atrial fibrillation, AF) over 10 years of follow-up in a multiethnic population
      (Multi-Ethnic Study of Atherosclerosis). METHODS: 5004 participants free of known
      CVD had magnetic resonance imaging (MRI) in 2000-2002. Cine images were analysed
      to compute, [Formula: see text] equivalent to LV volume/volume of sphere with
      length of LV as the diameter. The highest (greatest sphericity) and lowest
      (lowest sphericity) quintiles of SVI were compared against the reference group (2
      4 quintiles combined). Risk-factor adjusted hazard's ratio (HR) from Cox
      regression assessed the predictive performance of SVI at end-diastole (ED) and
      end-systole (ES) to predict incident outcomes over 10 years in retrospective
      interpretation of prospective data. RESULTS: At baseline, participants were aged
      61+/-10 years; 52% men and 39%/13%/26%/22% Cauc/Chinese/Afr-Amer/Hispanic. Low
      sphericity was associated with higher Framingham CVD risk, greater coronary
      calcium score and higher N-terminal pro-brain natriuretic peptide (NT-proBNP);
      while increased sphericity was associated with higher NT-proBNP and lower
      ejection fraction. Low sphericity predicted incident CHD (HR: 1.48, 1.55-2.59 at
      ED) and CVD (HR: 1.82, 1.47-2.27 at ED). However, both low (HR: 1.81, 1.20-2.73
      at ES) and high (HR: 2.21, 1.41-3.46 at ES) sphericity predicted incident HF.
      High sphericity also predicted AF. CONCLUSIONS: In a multiethnic population free
      of CVD at baseline, lowest sphericity was a predictor of incident CHD, CVD and HF
      over a 10-year follow-up period. Extreme sphericity was a strong predictor of
      incident HF and AF. SVI improved risk prediction models beyond established risk
      factors only for HF, but not for all CVD or CHD.

PMID- 27694111
TI  - The clinical efficacy and long-term prognostic value of stress echocardiography
      in octogenarians.
AB  - INTRODUCTION: Although stress echocardiography (SE) is invaluable in younger
      populations, its prognostic value may be attenuated in the elderly due to shorter
      life expectancy and the frequent presence of severe comorbidities. This study
      sought to evaluate the clinical effectiveness of SE in octogenarians,
      particularly its prognostic value over clinical variables, in predicting hard
      events. METHODS: A total of 374 consecutive octogenarians who underwent SE for
      evaluation of coronary artery disease (CAD) were assessed for feasibility,
      diagnostic accuracy and safety of the test, and followed up for hard outcomes
      (all-cause mortality, cardiovascular (CV) deaths and non-fatal myocardial
      infarction (NFMI)). Cox regression analysis was performed to identify predictors
      of outcome. RESULTS: Of the 374 tests, 360 (96.3%) were diagnostic. Of the 50
      patients with inducible ischaemia, 33 patients (66%) proceeded to angiography of
      which 27 (82%) patients had significant CAD. During long-term follow-up of 4.0+/
      2.0 years, there were 127 deaths and 36 NFMIs. The annualised mortality, NFMI and
      combined mortality /NFMI rates were 8.1%, 1.8% and 9.4% for patients with a
      normal SE and 12.1%, 5.5% and 14.1% for those with an abnormal SE, respectively.
      Predictors of NFMI on multivariate analysis were prior CAD (HR 2.89, CI 1.03 to
      8.15, p=0.045), peripheral vascular disease (HR 3.33, CI 1.18 to 9.45, p=0.02),
      and inducible ischaemia (HR 3.97, CI 1.49 to 10.55, p=0.006). In patients without
      prior history of CAD, inducible ischaemia was the only independent predictor of
      NFMI (HR 8.72, CI 1.46 to 52.2, p=0.018). The larger the extent of ischaemia, the
      greater the incidence of NFMI. The independent predictors of CV events (NFMI or
      CV mortality) were PAD (HR 2.81, CI 1.21 to 6.52, p=0.016) and peak wall motion
      score index (HR 5.71, CI 1.67 to 19.6, p=0.006). Although inducible ischaemia
      predicted all-cause mortality on unadjusted analysis, it did not on multivariate
      analysis. CONCLUSIONS: In octogenarians, SE demonstrated excellent feasibility,
      safety and diagnostic accuracy. SE parameters were independent predictors of NFMI
      and CV events, and the presence of inducible ischaemia was associated with a 50%
      increase in all-cause mortality.

PMID- 27694112
TI  - Evidence, experts, trustworthy guidelines and WikiRecs.

PMID- 27694113
TI  - Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of
      Selection.
AB  - Multi-parent populations (MPPs) capture and maintain the genetic diversity from
      multiple inbred founder strains to provide a resource for high-resolution genetic
      mapping through the accumulation of recombination events over many generations.
      Breeding designs that maintain a large effective population size with randomized
      assignment of breeders at each generation can minimize the impact of selection,
      inbreeding, and genetic drift on allele frequencies. Small deviations from
      expected allele frequencies will have little effect on the power and precision of
      genetic analysis, but a major distortion could result in reduced power and loss
      of important functional alleles. We detected strong transmission ratio distortion
      in the Diversity Outbred (DO) mouse population on chromosome 2, caused by meiotic
      drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The
      distorted region harbors thousands of polymorphisms derived from the seven non
      WSB founder strains and many of these would be lost if the sweep was allowed to
      continue. To ensure the utility of the DO population to study genetic variation
      on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at
      the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the
      drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed
      minimal disruption to allele frequencies across the rest of the autosomal genome.
      However, there was a shift in haplotype frequencies of the mitochondrial genome
      and an increase in the rate of an unusual sex chromosome aneuploidy. The DO
      population has been restored to genome-wide utility for genetic analysis, but our
      experience underscores that vigilant monitoring of similar genetic resource
      populations is needed to ensure their long-term utility.

PMID- 27694114
TI  - Epigenetic Control of Phenotypic Plasticity in the Filamentous Fungus Neurospora
      crassa.
AB  - Phenotypic plasticity is the ability of a genotype to produce different
      phenotypes under different environmental or developmental conditions. Phenotypic
      plasticity is a ubiquitous feature of living organisms, and is typically based on
      variable patterns of gene expression. However, the mechanisms by which gene
      expression is influenced and regulated during plastic responses are poorly
      understood in most organisms. While modifications to DNA and histone proteins
      have been implicated as likely candidates for generating and regulating
      phenotypic plasticity, specific details of each modification and its mode of
      operation have remained largely unknown. In this study, we investigated how
      epigenetic mechanisms affect phenotypic plasticity in the filamentous fungus
      Neurospora crassa By measuring reaction norms of strains that are deficient in
      one of several key physiological processes, we show that epigenetic mechanisms
      play a role in homeostasis and phenotypic plasticity of the fungus across a range
      of controlled environments. In general, effects on plasticity are specific to an
      environment and mechanism, indicating that epigenetic regulation is context
      dependent and is not governed by general plasticity genes. Specifically, we found
      that, in Neurospora, histone methylation at H3K36 affected plastic response to
      high temperatures, H3K4 methylation affected plastic response to pH, but H3K27
      methylation had no effect. Similarly, DNA methylation had only a small effect in
      response to sucrose. Histone deacetylation mainly decreased reaction norm
      elevation, as did genes involved in histone demethylation and acetylation. In
      contrast, the RNA interference pathway was involved in plastic responses to
      multiple environments.

PMID- 27694117
TI  - Radiation-Induced Cerebral Vascular "Malformations" at Biopsy.
AB  - Radiation-induced vascular "malformations", designated cavernous
      hemangiomas/cavernomas ("RICHs"), are seldom biopsied and are usually diagnosed
      based on neuroimaging features. They are an increasingly recognized complication
      of both CNS external beam radiation therapy and stereotactic radiosurgery. We
      identified 13 patients with radiation-induced vascular "malformations" in our
      surgical neuropathology databases searched from 2000 to 2016; 4 had received
      their therapy during childhood; 5 had received radiosurgery. Inclusion required
      identifiable vascular abnormalities on neuroimaging and/or, if recurrent tumor
      was additionally present, the vascular lesion had been a separately submitted
      specimen at the time of resection. Trichrome, and elastic stains and
      immunohistochemistry (IHC) for CD31, CD34, and smooth muscle actin (SMA) were
      performed. Five RICHs showed histological and IHC overlap with 12 non-radiation
      induced cavernomas; 8/13 had organizing coagulum containing recanalized
      vasculature and fibrinous deposits. Markedly altered vasculature in these 8
      lacked the back-to-back caverns typical of cavernomas; there was near absence of
      SMA immunopositivity in their ill-defined vessel walls. These coagulum-like
      lesions likely represented organized fibrinous exudates caused by subacute/remote
      radiation-induced fibrinoid vascular necrosis and vascular leakage. Thus, RICHs
      occur as 2 distinct histological types, without direct correlation between
      histological type and age at receipt, or type, of radiation. Two different
      etiological mechanisms likely underlie their pathogenesis.

PMID- 27694116
TI  - Male-Specific Transcription Factor Occupancy Alone Does Not Account for
      Differential Methylation at Imprinted Genes in the mouse Germ Cell Lineage.
AB  - Genomic imprinting is an epigenetic mechanism that affects a subset of mammalian
      genes, resulting in monoallelic expression depending on the parental origin of
      the alleles. Imprinted regions contain regulatory elements that are methylated in
      the gametes in a sex-specific manner (differentially methylated regions; DMRs).
      DMRs are present at nonimprinted loci as well, but whereas most regions are
      equalized after fertilization, methylation at imprinted regions maintains
      asymmetry. We tested the hypothesis that paternally unmethylated DMRs are
      occupied by transcription factors (TFs) present during male gametogenesis. Meta
      analysis of mouse RNA data to identify DNA-binding proteins expressed in male
      gametes and motif enrichment analysis of active promoters yielded a list of
      candidate TFs. We then asked whether imprinted or nonimprinted paternally
      unmethylated DMRs harbored motifs for these TFs, and found many shared motifs
      between the two groups. However, DMRs that are methylated in the male germ cells
      also share motifs with DMRs that remain unmethylated. There are recognition
      sequences exclusive to the unmethylated DMRs, whether imprinted or not, that
      correspond with cell-cycle regulators, such as p53. Thus, at least with the
      current available data, our results indicate a complex scenario in which TF
      occupancy alone is not likely to play a role in protecting unmethylated DMRs, at
      least during male gametogenesis. Rather, the epigenetic features of DMRs,
      regulatory sequences other than DMRs, and the role of DNA-binding proteins
      capable of endowing sequence specificity to DNA-methylating enzymes are feasible
      mechanisms and further investigation is needed to answer this question.

PMID- 27694115
TI  - Regulation of Secondary Metabolism by the Velvet Complex Is Temperature
      Responsive in Aspergillus.
AB  - Sensing and responding to environmental cues is critical to the lifestyle of
      filamentous fungi. How environmental variation influences fungi to produce a wide
      diversity of ecologically important secondary metabolites (SMs) is not well
      understood. To address this question, we first examined changes in global gene
      expression of the opportunistic human pathogen, Aspergillus fumigatus, after
      exposure to different temperature conditions. We found that 11 of the 37 SM gene
      clusters in A. fumigatus were expressed at higher levels at 30 degrees  than at
      37 degrees . We next investigated the role of the light-responsive Velvet complex
      in environment-dependent gene expression by examining temperature-dependent
      transcription profiles in the absence of two key members of the Velvet protein
      complex, VeA and LaeA We found that the 11 temperature-regulated SM gene clusters
      required VeA at 37 degrees  and LaeA at both 30 and 37 degrees  for wild-type
      levels of expression. Interestingly, four SM gene clusters were regulated by VeA
      at 37 degrees  but not at 30 degrees , and two additional ones were regulated by
      VeA at both temperatures but were substantially less so at 30 degrees ,
      indicating that the role of VeA and, more generally of the Velvet complex, in the
      regulation of certain SM gene clusters is temperature-dependent. Our findings
      support the hypothesis that fungal secondary metabolism is regulated by an
      intertwined network of transcriptional regulators responsive to multiple
      environmental factors.

PMID- 27694118
TI  - Core Principles of Quality Improvement and Patient Safety.

PMID- 27694119
TI  - Eye Pain in Children.
AB  - Primary care physicians are often the first to see a child with the complaint of
      eye pain. The eye examination in children is not easy, and the entities that can
      cause pain in children range from a foreign body in the cornea to the most
      serious amblyogenic (inducing decreased vision) and life-threatening conditions.
      Eye pain is a red flag for ocular and systemic conditions, either in a "quiet
      eye" or "red eye." A detailed history of present illness; pertinent review of
      systems; close attention to the past medical, family, and social histories; and
      meticulous physical examination can help to determine the cause, establish the
      correct treatment, and serve as the basis for referral to a pediatric
      ophthalmologist if necessary.

PMID- 27694120
TI  - Hepatitis A, B, and C.

PMID- 27694122
TI  - Corrections.

PMID- 27694121
TI  - Case 1: Prolonged Nasal Discharge and Facial Pain in a 17-year-old Girl.

PMID- 27694123
TI  - Case 2: Aspiration Pneumonia in a 16-year-old Girl.

PMID- 27694124
TI  - Case 3: Chest Pain and Syncope in an 11-year-old Boy.

PMID- 27694125
TI  - Sentinel Events/Patient Safety Events.

PMID- 27694126
TI  - Visual Diagnosis: Infant with Ecchymoses.

PMID- 27694127
TI  - Meaningful Effect Sizes, Intraclass Correlations, and Proportions of Variance
      Explained by Covariates for Planning Two- and Three-Level Cluster Randomized
      Trials of Social and Behavioral Outcomes.
AB  - BACKGROUND: There is a need for greater guidance regarding design parameters and
      empirical benchmarks for social and behavioral outcomes to inform assumptions in
      the design and interpretation of cluster randomized trials (CRTs). OBJECTIVES: We
      calculated the empirical reference values on critical research design parameters
      associated with statistical power for children's social and behavioral outcomes,
      including effect sizes, intraclass correlations (ICCs), and proportions of
      variance explained by a covariate at different levels (R 2). SUBJECTS: Children
      from kindergarten to Grade 5 in the samples from four large CRTs evaluating the
      effectiveness of two classroom- and two school-level preventive interventions.
      MEASURES: Teacher ratings of students' social and behavioral outcomes using the
      Teacher Observation of Classroom Adaptation-Checklist and the Social Competence
      Scale-Teacher. RESEARCH DESIGN: Two types of effect size benchmarks were
      calculated: (1) normative expectations for change and (2) policy-relevant
      demographic performance gaps. The ICCs and R 2 were calculated using two-level
      hierarchical linear modeling (HLM), where students are nested within schools, and
      three-level HLM, where students were nested within classrooms, and classrooms
      were nested within schools. RESULTS AND CONCLUSIONS: Comprehensive tables of
      benchmarks and ICC values are provided to inform prevention researchers in
      interpreting the effect size of interventions and conduct power analyses for
      designing CRTs of children's social and behavioral outcomes. The discussion also
      provides a demonstration for how to use the parameter reference values provided
      in this article to calculate the sample size for two- and three-level CRTs
      designs.

PMID- 27694128
TI  - Reviewing the Reviews: Examining Similarities and Differences Between Federally
      Funded Evidence Reviews.
AB  - BACKGROUND: The federal government's emphasis on supporting the implementation of
      evidence-based programs has fueled a need to conduct and assess rigorous
      evaluations of programs. Through partnerships with researchers, policy makers,
      and practitioners, evidence reviews-projects that identify, assess, and summarize
      existing research in a given area-play an important role in supporting the
      quality of these evaluations and how the findings are used. These reviews
      encourage the use of sound scientific principles to identify, select, and
      implement evidence-based programs. The goals and standards of each review
      determine its conclusions about whether a given evaluation is of high quality or
      a program is effective. It can be difficult for decision makers to synthesize the
      body of evidence when faced with results from multiple program evaluations.
      SAMPLE: This study examined 14 federally funded evidence reviews to identify
      commonalities and differences in their assessments of evidence of effectiveness.
      FINDINGS: There were both similarities and significant differences across the
      reviews. In general, the evidence reviews agreed on the broad critical elements
      to consider when assessing evaluation quality, such as research design, low
      attrition, and baseline equivalence. The similarities suggest that, despite
      differences in topic and the availability of existing research, reviews typically
      favor evaluations that limit potential bias in their estimates of program
      effects. However, the way in which some of the elements were assessed, such as
      what constituted acceptable amounts of attrition, differed. Further, and more
      substantially, the reviews showed greater variation in how they conceptualized
      "effectiveness."

PMID- 27694129
TI  - Effect of Interstitial Fluid Pressure on Ultrasound Axial Strain and Axial Shear
      Strain Elastography.
AB  - Ultrasound elastography is an imaging modality that has been used to diagnose
      tumors of the breast, thyroid, and prostate. Both axial strain elastography and
      axial shear strain elastography (ASSE) have shown significant potentials to
      differentiate between benign and malignant tumors. Elevated interstitial fluid
      pressure (IFP) is a characteristic of many malignant tumors and a major barrier
      in targeted drug delivery therapies. This parameter, however, has not received
      significant attention in ultrasound elastography and, in general, in most
      diagnostic imaging modalities yet. In this paper, we investigate the effect of an
      underlying IFP contrast on ultrasound axial strain and axial shear strain imaging
      using finite element analysis. Our results show that an underlying contrast in
      IFP creates a new contrast mechanism in both the axial strain and axial shear
      strain elastographic images. This information might be important for a better
      interpretation of elastographic images of tumors.

PMID- 27694131
TI  - Medical school "banter" denigrating GPs and psychiatrists must stop, say college
      heads.

PMID- 27694130
TI  - Clinical and Histologic Predictive Factors of Response to Induction Chemotherapy
      in Head and Neck Squamous Cell Carcinoma.
AB  - Objectives: Induction chemotherapy (IC) is occasionally used in head and neck
      cancer, leading to less extensive surgery and reduced need for irradiation.
      Factors predicting the response to IC have not been determined. In this study, we
      investigated the clinical and histopathologic factors that predict the response
      to IC. Methods: Head and neck squamous cell carcinomas from 81 patients were
      analyzed; clinical factors, histologic parameters, and expression of p16 and p53
      were correlated with response to chemotherapy and prognosis. Results: Factors
      predicting a good response to IC were the nonoropharyngeal localization, a rich
      lymphocytic tissue response, and a low platelet-to-lymphocyte blood ratio before
      treatment. Response to IC did not correlate with prognosis, whereas a low
      neutrophil-to-lymphocyte ratio (NLR), the absence of a desmoplastic reaction, a
      rich lymphocytic tissue response, and the overexpression of p53 were associated
      with better prognosis. Conclusions: Lymphocytic tissue response, NLR, and
      nonoropharyngeal localization are factors predictive of response to IC.

PMID- 27694133
TI  - ERRATUM.

PMID- 27694132
TI  - Regulation and Essentiality of the StAR-related Lipid Transfer (START) Domain
      containing Phospholipid Transfer Protein PFA0210c in Malaria Parasites.
AB  - StAR-related lipid transfer (START) domains are phospholipid- or sterol-binding
      modules that are present in many proteins. START domain-containing proteins
      (START proteins) play important functions in eukaryotic cells, including the
      redistribution of phospholipids to subcellular compartments and delivering
      sterols to the mitochondrion for steroid synthesis. How the activity of the START
      domain is regulated remains unknown for most of these proteins. The Plasmodium
      falciparum START protein PFA0210c (PF3D7_0104200) is a broad-spectrum
      phospholipid transfer protein that is conserved in all sequenced Plasmodium
      species and is most closely related to the mammalian START proteins STARD2 and
      STARD7. PFA0210c is unusual in that it contains a signal sequence and a PEXEL
      export motif that together mediate transfer of the protein from the parasite to
      the host erythrocyte. The protein also contains a C-terminal extension, which is
      very uncommon among mammalian START proteins. Whereas the biochemical properties
      of PFA0210c have been characterized, the function of the protein remains unknown.
      Here, we provide evidence that the unusual C-terminal extension negatively
      regulates phospholipid transfer activity. Furthermore, we use the genetically
      tractable Plasmodium knowlesi model and recently developed genetic technology in
      P. falciparum to show that the protein is essential for growth of the parasite
      during the clinically relevant asexual blood stage life cycle. Finally, we show
      that the regulation of phospholipid transfer by PFA0210c is required in vivo, and
      we identify a potential second regulatory domain. These findings provide insight
      into a novel mechanism of regulation of phospholipid transfer in vivo and may
      have important implications for the interaction of the malaria parasite with its
      host cell.

PMID- 27694134
TI  - ERRATUM.

PMID- 27694135
TI  - ERRATUM.

PMID- 27694136
TI  - RNAEditor: easy detection of RNA editing events and the introduction of editing
      islands.
AB  - RNA editing of adenosine residues to inosine ('A-to-I editing') is the most
      common RNA modification event detectible with RNA sequencing (RNA-seq). While not
      directly detectable, inosine is read by next-generation sequencers as guanine.
      Therefore, mapping RNA-seq reads to their corresponding reference genome can
      detect potential editing events by identifying 'A-to-G' conversions. However, one
      must exercise caution when searching for editing sites, as A-to-G conversions
      also arise from sequencing errors as well as mutations. To address these
      complexities, several algorithms and software products have been developed to
      accurately identify editing events. Here, we survey currently available methods
      to analyze RNA editing events and introduce a new easy-to-use bioinformatics tool
      'RNAEditor' for the detection of RNA editing events. During the development of
      RNAEditor, we noticed editing often happened in clusters, which we named 'editing
      islands'. We developed a clustering algorithm to find editing islands and
      included it in RNAEditor. RNAEditor is freely available at http://rnaeditor.uni
      frankfurt.de. We anticipate that RNAEditor will provide biologists with an easy
      to-use tool for studying RNA editing events and the newly defined editing
      islands.

PMID- 27694137
TI  - Longitudinal examination of temporality in the association between chronic
      disease diagnosis and changes in work status and hours worked.
AB  - OBJECTIVES: To examine the longitudinal relationship between incidence of
      diagnosed chronic disease and work status and hours worked. METHODS: A dynamic
      cohort approach was taken to construct our study sample using the Canadian
      National Population Health Survey. Participant inclusion criteria included being
      employed and without a chronic health condition in the survey cycle prior to
      diagnosis, and participation in consecutive surveys following diagnosis. Each
      respondent was matched with up to 5 respondents without a diagnosed health
      condition. The direct and indirect associations between chronic disease and work
      status and hours worked following diagnosis were examined using probit and linear
      regression path models. Separate models were developed for arthritis, back
      problems, diabetes, hypertension and heart disease. RESULTS: We identified 799
      observations with a diagnosis of arthritis, 858 with back pain, 178 with
      diabetes, 569 with hypertension and 163 with heart disease, which met our
      selection criteria. An examination of total effects at time 1 and time 2 showed
      that, excluding hypertension, chronic disease diagnosis was related to work loss.
      The time 2 effect of chronic disease diagnosis on work loss was mediated through
      time 1 work status. With the exception of heart disease, an incident case of
      chronic disease was not related to changes in work hours among observations with
      continuous work participation. CONCLUSIONS: Chronic disease can result in work
      loss following diagnosis. Research is required to understand how modifying
      occupational conditions may benefit employment immediately after diagnosis.

PMID- 27694138
TI  - Comparative Characterization of Biomechanical Behavior and Healing Profile of a
      Novel Ultra-High-Molecular-Weight Amorphous Poly-l-Lactic Acid Sirolimus-Eluting
      Bioresorbable Coronary Scaffold.
AB  - BACKGROUND: Clinically available bioresorbable scaffolds (BRS) rely on polymer
      crystallinity to achieve mechanical strength resulting in limited overexpansion
      capabilities and structural integrity when exposed to high-loading conditions. We
      aimed to evaluate the biomechanical behavior and vascular healing profile of a
      novel, sirolimus-eluting, high-molecular-weight, amorphous poly-l-lactic acid
      based BRS (Amaranth BRS). METHODS AND RESULTS: In vitro biomechanical testing was
      performed under static and cyclic conditions. A total of 99 devices (65 Amaranth
      BRS versus 34 Absorb bioresorbable vascular scaffold [BVS]) were implanted in 99
      coronary arteries of 37 swine for pharmacokinetics and healing evaluation at
      various time points. In the Absorb BVS, the number of fractures per scaffold seen
      on light microscopy was 6.0 (5.0-10.5) when overexpanded 1.0 mm above nominal
      values (~34%). No fractures were observed in the Amaranth BRS group at 1.3 mm
      above nominal values (~48% overexpansion). The number of fractures was higher in
      the Absorb BVS on accelerated cycle testing over time (at 24K cycles=5.0 [5.0
      9.0] Absorb BVS versus 0.0 [0.0-0.5] Amaranth BRS). Approximately 90% of
      sirolimus was found to be eluted by 90 days. Optical coherence tomography
      analysis demonstrated lower percentages of late scaffold recoil in the Amaranth
      BRS at 3 months (Amaranth BRS=-10+/-16.1% versus Absorb BVS=10.7+/-13.2%;
      P=0.004). Histopathology analysis revealed comparable levels of vascular healing
      and inflammatory responses between both BRSs up to 6 months. CONCLUSIONS: New
      generation high-molecular-weight amorphous poly-l-lactic acid scaffolds have the
      potential to improve the clinical performance of BRS and provide the ideal
      platform for the future miniaturization of the technology.

PMID- 27694139
TI  - Mindfulness and headache: A "new" old treatment, with new findings.
AB  - Background Mindfulness refers to a host of procedures that have been practiced
      for centuries, but only recently have begun to be applied to varied pain
      conditions, with the most recent being headache. Methods We reviewed research
      that incorporated components of mindfulness for treating pain, with a more in
      depth focus on headache disorders. We also examined literature that has closely
      studied potential physiological processes in the brain that might mediate the
      effects of mindfulness. We report as well preliminary findings of our ongoing
      trial comparing mindfulness alone to pharmacological treatment alone for treating
      chronic migraine accompanied by medication overuse. Results Although research
      remains in its infancy, the initial findings support the utility of varied
      mindfulness approaches for enhancing usual care for headache management. Our
      preliminary findings suggest mindfulness by itself may produce effects comparable
      to that of medication alone for patients with chronic migraine and medication
      overuse. Conclusions Much work remains to more fully document the role and long
      term value of mindfulness for specific headache types. Areas in need of further
      investigation are discussed.

PMID- 27694140
TI  - Silencing of SRA1 Regulates ER Expression and Attenuates the Growth of Stromal
      Cells in Ovarian Endometriosis.
AB  - Estradiol and its nuclear receptors, estrogen receptor (ER) alpha and ER-beta,
      have important functions in endometriosis, and the transcriptional activity of
      these receptors is modulated by coactivators and corepressors. The steroid
      receptor RNA activator 1 (SRA1) produces SRA long noncoding RNA (lncRNA) and SRA
      protein (SRAP), which regulate ER expression at the RNA and protein levels in
      some hormone-dependent tumors via an alternative splicing event. However, only a
      few are reported on their expressions in endometriosis. Here, we observed that
      low expression levels of SRA lncRNA and ER-alpha but relatively high expression
      levels of SRAP and ER-beta were detected in ovarian endometriotic tissues versus
      normal endometrial tissues. Steroid receptor RNA activator 1-small interfering
      RNA treatment significantly increased ER-alpha levels but reduced ER-beta levels
      in endometriotic stromal cells (ESCs). Furthermore, the treatment can also
      attenuate the proliferation and promote early apoptosis in these cells. Our
      results indicate that the regulation of ER via SRA in ovarian endometriosis may
      play a significant role in the growth of ESCs.

PMID- 27694141
TI  - Hypoxia-inducible factor-2alpha plays a role in mediating oesophagitis in GORD.
AB  - OBJECTIVE: In an earlier study wherein we induced acute reflux by interrupting
      proton pump inhibitor (PPI) therapy in patients with reflux oesophagitis (RO)
      healed by PPIs, we refuted the traditional concept that RO develops as an acid
      burn. The present study explored our alternative hypothesis that RO results from
      reflux-stimulated production of pro-inflammatory molecules mediated by hypoxia
      inducible factors (HIFs). DESIGN: Using oesophageal biopsies taken from patients
      in our earlier study at baseline and at 1 and 2 weeks off PPIs, we immunostained
      for HIF-1alpha, HIF-2alpha and phospho-p65, and measured pro-inflammatory
      molecule mRNAs. We exposed human oesophageal squamous cell lines to acidic bile
      salts, and evaluated effects on HIF activation, p65 function, pro-inflammatory
      molecule production and immune cell migration. RESULTS: In patient biopsies,
      increased immunostaining for HIF-2alpha and phospho-p65, and increased pro
      inflammatory molecule mRNA levels were seen when RO redeveloped 1 or 2 weeks
      after stopping PPIs. In oesophageal cells, exposure to acidic bile salts
      increased intracellular reactive oxygen species, which decreased prolyl
      hydroxylase function and stabilised HIF-2alpha, causing a p65-dependent increase
      in pro-inflammatory molecules; conditioned media from these cells increased T
      cell migration rates. HIF-2alpha inhibition by small hairpin RNA or selective
      small molecule antagonist blocked the increases in pro-inflammatory molecule
      expression and T cell migration induced by acidic bile salts. CONCLUSIONS: In
      patients developing RO, increases in oesophageal HIF-2alpha correlate with
      increased pro-inflammatory molecule expression. In oesophageal epithelial cells,
      acidic bile salts stabilise HIF-2alpha, which mediates expression of pro
      inflammatory molecules. HIF-2alpha appears to have a role in RO pathogenesis.
      TRIAL REGISTRATION NUMBER: NCT01733810; Results.

PMID- 27694143
TI  - Prevention of progression from small to large varices: are we there yet? An
      updated meta-analysis.

PMID- 27694142
TI  - Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota
      signatures in inflammatory bowel disease.
AB  - OBJECTIVE: An inadequate host response to the intestinal microbiota likely
      contributes to the manifestation and progression of human inflammatory bowel
      disease (IBD). However, molecular approaches to unravelling the nature of the
      defective crosstalk and its consequences for intestinal metabolic and
      immunological networks are lacking. We assessed the mucosal transcript levels,
      splicing architecture and mucosa-attached microbial communities of patients with
      IBD to obtain a comprehensive view of the underlying, hitherto poorly
      characterised interactions, and how these are altered in IBD. DESIGN: Mucosal
      biopsies from Crohn's disease and patients with UC, disease controls and healthy
      individuals (n=63) were subjected to microbiome, transcriptome and splicing
      analysis, employing next-generation sequencing. The three data levels were
      integrated by different bioinformatic approaches, including systems biology
      inspired network and pathway analysis. RESULTS: Microbiota, host transcript
      levels and host splicing patterns were influenced most strongly by tissue
      differences, followed by the effect of inflammation. Both factors point towards a
      substantial disease-related alteration of metabolic processes. We also observed a
      strong enrichment of splicing events in inflamed tissues, accompanied by an
      alteration of the mucosa-attached bacterial taxa. Finally, we noted a striking
      uncoupling of the three molecular entities when moving from healthy individuals
      via disease controls to patients with IBD. CONCLUSIONS: Our results provide
      strong evidence that the interplay between microbiome and host transcriptome,
      which normally characterises a state of intestinal homeostasis, is drastically
      perturbed in Crohn's disease and UC. Consequently, integrating multiple OMICs
      levels appears to be a promising approach to further disentangle the complexity
      of IBD.

PMID- 27694145
TI  - A Borrelia afzelii Infection Increases Larval Tick Burden on Myodes glareolus
      (Rodentia: Cricetidae) and Nymphal Body Weight of Ixodes ricinus (Acari:
      Ixodidae).
AB  - Several microorganisms have been shown to manipulate their host or vector to
      enhance their own transmission. Here we examined whether an infection with
      Borrelia afzelii affects its transmission between its bank vole (Myodes
      glareolus, Schreber, 1780) host and tick vector. Captive-bred bank voles were
      inoculated with B. afzelii or control medium, after which host preference of
      Ixodes ricinus L. nymphs was determined in a Y-tube olfactometer. Thereafter,
      infected and uninfected bank voles were placed in a semifield arena containing
      questing larvae to measure larval tick attachment. Engorged larvae were collected
      from these bank voles, molted into nymphs, weighed, and analyzed for infection by
      PCR.Nymphs were attracted to the odors of a bank vole compared to ambient air and
      preferred the odors of an infected bank vole over that of an uninfected bank
      vole. In the semifield arena, infected male bank voles had greater larval tick
      burdens then uninfected males, while similar larval tick burdens were observed on
      females regardless of infection status. Nymphal ticks that acquired a B. afzelii
      infection had higher body weight than nymphs that did not acquire an infection
      regardless of the infection status of the vole. These results show that a B.
      afzelii infection in bank voles increases larval tick burden and that a B.
      afzelii infection in larvae increases nymphal body weight. This finding provides
      novel ecological insights into the enzootic cycle of B. afzelii.

PMID- 27694147
TI  - A Comparison of Pain Beliefs and Coping Strategies and Their Association with
      Chronic Pain Adjustment Between Singapore and United States.
AB  - Objectives: Research examining the importance of pain beliefs and coping
      strategies to chronic pain adjustment has been performed almost exclusively using
      Western populations. The purpose of this study was to examine empirically the
      generalizability of this research to Singapore. Methods: Employing a cross
      sectional design, measures assessing pain beliefs, coping strategies, pain
      intensity, pain interference, and depressive symptoms were administered to 101
      patients with chronic pain from Singapore. Analyses examined the means of belief
      and coping strategies measures and their associations with measures of pain
      intensity, pain interference, and depressive symptoms and compared the results
      with the data of a sample of 100 patients with chronic pain from a previously
      published study from the United States. Results: Mean differences between the
      Singapore and US samples were found for four of the seven belief scales, and four
      of the eight coping scales. When significant, associations between belief and
      coping strategies with measures of pain and dysfunction were in the hypothesized
      directions in both samples. We also found that the strength of four out of 30 of
      the associations between beliefs/coping strategies and measures of pain and
      dysfunction were different between the Singapore and US samples. Conclusion: The
      findings provide further support for the potential influence of culture on how
      individuals view and cope with pain. However, the many similarities found in
      direction and strength of the associations between beliefs/coping strategies and
      measures of pain/dysfunction provide preliminary support for the appropriateness
      of the use of cognitive behavioral therapy developed in the United States with
      the Singapore population.

PMID- 27694148
TI  - Role of Magnetic Resonance Imaging in Ascertaining the Success of Transforaminal
      Epidural Steroid Injection for Lumbar Radicular Pain.
AB  - Objective: To explore the outcome differences of lumbar transforaminal epidural
      steroid injection (TFESI) according to magnetic resonance imaging (MRI) findings
      in patients with lumbar radicular pain. Design: Retrospective study. Setting:
      Single university-based interventional pain management unit. Patients: Fifty-nine
      patients who had lumbar radicular pain with a recent lumbar MRI and three-month
      follow-up were included. Methods: MRI findings were reviewed for the following
      items: herniation type (bulging, protrusion, extrusion), herniation location
      (central, subarticular, foraminal, extraforaminal), high intensity zone (HIZ),
      and nerve root impingement (NRI). Pain severity was evaluated using a visual
      analogue scale (VAS) at time of before injection, then two weeks and three months
      after. Results: Pain scores improved significantly in each group ( P  < 0.05) at
      all time points, but there were no statistically significant differences in
      improvements according to type or location of disc herniation. Pain scores were
      significantly lower in patients with HIZ at the second week and in patients with
      NRI at the third month ( P  < 0.05). Conclusions: TFESI was an effective
      treatment method in patients with radicular pain, irrespective of the type or
      location of disc herniation. However, greater improvement in pain may be expected
      at the second week in patients with HIZ and at the third month in patients with
      NRI.

PMID- 27694149
TI  - Self-Reported Presence and Experience of Pain in Adults with Down Syndrome.
AB  - Objective: The aim was to examine whether the presence of pain (based on physical
      conditions and participants' report) and self-reported pain experience in adults
      with Down syndrome (DS) differ from general population controls. Design: Cross
      sectional study of 224 adults with DS (mean age = 38.1 years, mild-severe
      intellectual disabilities) and 142 age-matched controls (median age = 40.5 years,
      mean estimated IQ = 105.7) in the Netherlands. Methods: File-based medical
      information was evaluated. Self-reported presence and experience of pain were
      assessed in rest and after movement during a test session (affect with facial
      affective scale (FAS: 0.04-0.97), intensity assessed with numeric rating scale
      (NRS: 0-10). Results: Compared with controls, more DS participants had physical
      conditions that may cause pain and/or discomfort ( p  = .004, 50% vs 35%), but
      fewer DS participants reported pain during the test session ( p  = .003, 58% vs
      73%). Of the participants who indicated pain and comprehended self-reporting
      scales ( n  = 198 FAS, n  = 161 NRS), the DS group reported a higher pain affect
      and intensity than the controls ( p  < .001, FAS: 0.75-0.85 vs 0.50-0.59, NRS:
      6.00-7.94 vs 2.00-3.73). Conclusions: Not all adults with DS and
      painful/discomforting physical conditions reported pain. Those who did indicated
      a higher pain experience than adults from the general population. Research into
      spontaneous self-report of pain, repeated pain assessment, and acute pain is
      needed in people with DS for more insight into pain experience and mismatches
      between self-report and medical information.

PMID- 27694150
TI  - The Cost of Serious Patient Fall-Related Injuries at Hospitals in Turkey: A
      Matched Case-Control Study.
AB  - Patient falls cause economic loss in hospitals, as well as patient injuries. This
      study aimed to calculate the additional hospital cost and length of stay (LOS)
      due to fall-related serious injuries and to identify the determining factors for
      both outcomes. A matched case-control design was used in the study. It was
      conducted with a case group of 39 patients and a control group of 39 patients in
      28 hospitals in Izmir, Turkey. The additional hospital cost and LOS due to fall
      related serious injuries were calculated to be US$3,302.60 and 14.61 days,
      respectively. Precautionary initiatives for the injurious falls can prevent
      patients from getting injured and avoid increases in cost and LOS due to these
      injuries.

PMID- 27694153
TI  - Effect of Residual Bacteria on the Outcome of Pulp Regeneration In Vivo.
AB  - It is not known to what extent residual infection may interfere with the success
      of pulp regeneration procedures. The aim of this study was to determine,
      radiographically and histologically, the effect of residual bacteria on the
      outcome of pulp regeneration mediated by a tissue-engineered construct as
      compared with traditional revascularization. Periapical lesions were induced in
      24 canine teeth of 6 ferrets. After disinfection with 1.25% NaOCl and triple
      antibiotic paste, ferret dental pulp stem cells, encapsulated in a hydrogel
      scaffold, were injected into half the experimental teeth. The other half were
      treated with the traditional revascularization protocol with a blood clot
      scaffold. After 3 mo, block sections of the canine teeth were imaged
      radiographically and processed for histologic and histobacteriologic analyses.
      Associations between variables of interest were evaluated through mixed effects
      regression models. There were no significant differences between the 2
      experimental groups in radiographic root development ( P > 0.05). There was a
      significant association between the presence of persistent periapical
      radiolucency and root wall thickness ( P = 0.02). There was also no significant
      difference in histologic findings between the 2 experimental groups ( P > 0.05).
      The presence of residual bacteria was significantly associated with lack of
      radiographic growth ( P < 0.001). The amount of dentin-associated mineralized
      tissue formed in teeth with residual bacteria was significantly less than in
      teeth with no residual bacteria ( P < 0.001). Residual bacteria have a critical
      negative effect on the outcome of regenerative endodontic procedures.

PMID- 27694151
TI  - Anterior Shoulder Instability in the Military Athlete.
AB  - CONTEXT: Given its young, predominately male demographics and intense physical
      demands, the US military remains an ideal cohort for the study of anterior
      shoulder instability. EVIDENCE ACQUISITION: A literature search of PubMed,
      MEDLINE, and the Cochrane Database was performed to identify all peer-reviewed
      publications from 1950 to 2016 from US military orthopaedic surgeons focusing on
      the management of anterior shoulder instability. STUDY DESIGN: Clinical review.
      LEVEL OF EVIDENCE: Level 4. RESULTS: The incidence of anterior shoulder
      instability events in the military occurs at an order of magnitude greater than
      in civilian populations, with rates as high as 3% per year among high-risk
      groups. With more than 90% risk of a Bankart lesion and high risk for instability
      recurrence, the military has advocated for early intervention of first-time
      shoulder instability while documenting up to 76% relative risk reduction versus
      nonoperative treatment. Preoperative evaluation with advanced radiographic
      imaging should be used to evaluate for attritional bone loss or "off-track"
      engaging defects to guide comprehensive surgical management. With complex
      recurrent shoulder instability and/or cases of clinically significant osseous
      lesions, potential options such as remplissage, anterior open capsular
      procedures, or bone augmentation procedures may be preferentially considered.
      CONCLUSION: Careful risk stratification, clinical evaluation, and selective
      surgical management for at-risk military patients with anterior shoulder
      instability can optimize the recurrence risk and functional outcome in this
      population.

PMID- 27694154
TI  - Extracellular ATP Induces Calcium Signaling in Odontoblasts.
AB  - Odontoblasts form dentin at the outermost surface of tooth pulp. An increasing
      level of evidence in recent years, along with their locational advantage,
      implicates odontoblasts as a secondary role as sensory or immune cells.
      Extracellular adenosine triphosphate (ATP) is a well-characterized signaling
      molecule in the neuronal and immune systems, and its potential involvement in
      interodontoblast communications was recently demonstrated. In an effort to
      elaborate the ATP-mediated signaling pathway in odontoblasts, the current study
      performed single-cell reverse transcription polymerase chain reaction (RT-PCR)
      and immunofluorescent detection to investigate the expression of ATP receptors
      related to calcium signal in odontoblasts from incisal teeth of 8- to 10-wk-old
      rats, and demonstrated an in vitro response to ATP application via calcium
      imaging experiments. While whole tissue RT-PCR analysis detected P2Y2, P2Y4, and
      all 7 subtypes (P2X1 to P2X7) in tooth pulp, single-cell RT-PCR analysis of
      acutely isolated rat odontoblasts revealed P2Y2, P2Y4, P2X2, P2X4, P2X6, and P2X7
      expression in only a subset (23% to 47%) of cells tested, with no evidence for
      P2X1, P2X3, and P2X5 expression. An increase of intracellular Ca2+ concentration
      in response to 100MUM ATP, which was repeated after pretreatment of thapsigargin
      or under the Ca2+-free condition, suggested function of both ionotropic and
      metabotropic ATP receptors in odontoblasts. The enhancement of ATP-induced
      calcium response by ivermectin and inhibition by 5-(3-bromophenyl)-1,3-dihydro-2H
      benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD) confirmed a functional P2X4 subtype
      in odontoblasts. Positive calcium response to 2',3'-O-(benzoyl-4-benzoyl)-ATP
      (BzATP) and negative response to alpha,beta-methylene ATP suggested P2X2, P2X4,
      and P2X7 as functional subunits in rat odontoblasts. Single-cell RT-PCR analysis
      of the cells with confirmed calcium response and immunofluorescent detection
      further corroborated the expression of P2X4 and P2X7 in odontoblasts. Overall,
      this study demonstrated heterogeneous expression of calcium-related ATP receptor
      subtypes in subsets of individual odontoblasts, suggesting extracellular ATP as a
      potential signal mediator for odontoblastic functions.

PMID- 27694152
TI  - TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia.
AB  - Hyperphosphorylated transactive response DNA-binding protein 43 (TDP-43, encoded
      by TARDBP ) proteinopathy has recently been described in ageing and in
      association with cognitive impairment, especially in the context of Alzheimer's
      disease pathology. To explore the role of mixed Alzheimer's disease and TDP-43
      pathologies in clinical Alzheimer's-type dementia, we performed a comprehensive
      investigation of TDP-43, mixed pathologies, and clinical Alzheimer's-type
      dementia in a large cohort of community-dwelling older subjects. We tested the
      hypotheses that TDP-43 with Alzheimer's disease pathology is a common mixed
      pathology; is related to increased likelihood of expressing clinical Alzheimer's
      type dementia; and that TDP-43 pathologic stage is an important determinant of
      clinical Alzheimer's-type dementia. Data came from 946 older adults with ( n =
      398) and without dementia ( n = 548) from the Rush Memory and Aging Project and
      Religious Orders Study. TDP-43 proteinopathy (cytoplasmic inclusions) was present
      in 496 (52%) subjects, and the pattern of deposition was classified as stage 0
      (none; 48%), stage 1 (amygdala; 18%), stage 2 (extension to
      hippocampus/entorhinal; 21%), or stage 3 (extension to neocortex; 14%). TDP-43
      pathology combined with a pathologic diagnosis of Alzheimer's disease was a
      common mixed pathology (37% of all participants), and the proportion of subjects
      with clinical Alzheimer's-type dementia formerly labelled 'pure pathologic
      diagnosis of Alzheimer's disease' was halved when TDP-43 was considered. In
      logistic regression models adjusted for age, sex, and education, TDP-43 pathology
      was associated with clinical Alzheimer's-type dementia (odds ratio = 1.51, 95%
      confidence interval = 1.11, 2.05) independent of pathological Alzheimer's disease
      (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies
      (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis). Mixed
      Alzheimer's disease and TDP-43 pathologies were associated with higher odds of
      clinical Alzheimer's-type dementia (odds ratio = 6.73, 95% confidence interval =
      4.18, 10.85) than pathologic Alzheimer's disease alone (odds ratio = 4.62, 95%
      confidence interval = 2.84, 7.52). In models examining TDP-43 stage, a dose
      response relationship with clinical Alzheimer's-type dementia was observed, and a
      significant association was observed starting at stage 2, extension beyond the
      amygdala. In this large sample from almost 1000 community participants, we
      observed that TDP-43 proteinopathy was very common, frequently mixed with
      pathological Alzheimer's disease, and associated with a higher likelihood of the
      clinical expression of clinical Alzheimer's-type dementia but only when extended
      beyond the amygdala.

PMID- 27694155
TI  - DRN and TRAMP degrade specific and overlapping aberrant mRNAs formed at various
      stages of mRNP biogenesis in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, nuclear exosome along with TRAMP and DRN selectively
      eliminates diverse aberrant messages. These decay apparatuses appear to operate
      as independent mechanisms in the nucleus. Here, using genetic and molecular
      approach we systematically investigate the functional relationship between
      exosome, TRAMP and DRN mechanisms by examining their relative contributions in
      the degradation of diverse classes of aberrant nuclear mRNAs generated at various
      phases of mRNP biogenesis. Our findings suggest that nuclear exosome in
      association with the TRAMP complex exclusively degrades the transcription
      assembly-defective mRNPs and splice-defective intron-containing pre-mRNAs,
      whereas nuclear exosome along with DRN solely degrades the export-defective
      messages. The degradation of aberrant read-through transcripts with 3'
      extensions, in contrast, requires the activity of TRAMP and DRN together along
      with nuclear exosome function. Thus, the profile of substrate specificity of
      these nuclear decay machines reflects dependency of the nuclear exosome for
      either TRAMP or DRN function to degrade distinct nuclear mRNAs. We propose that
      DRN apparatus may act as a novel ancillary factor required for the nuclear
      exosome function to degrade specific classes of aberrant messages.

PMID- 27694156
TI  - eIF4G-an integrator of mRNA metabolism?
AB  - The eukaryotic translation initiation factor, eIF4G, plays a key functional role
      in the initiation of cap-dependent translation by acting as an adapter to
      nucleate the assembly of eIF4F complex. Together with poly(A)-binding protein and
      eIF3, eIF4F subsequently triggers the recruitment of 43S ribosomal pre-initiation
      complex to the messenger RNA template. Since eukaryotes primarily regulate
      translation at the level of initiation, eIF4G is implicated in the control of
      eukaryotic gene expression. Remarkably, emerging evidence in Saccharomyces
      cerevisiae indicates that eIF4G also plays a key role in nuclear mRNA biogenesis
      and surveillance-a finding that is in agreement with its nuclear distribution.
      Here, we focus on the functional involvement of eIF4G in the nucleus in
      modulating pre-mRNA splicing, mRNA surveillance and possibly in much-debated
      nuclear translation. Notably, the nature of the biochemical role of this protein
      in the major events of cellular mRNA metabolism emphasizes that this crucial
      protein factor may serve as a general integrator of mRNA functional states by
      acting as an adapter molecule.

PMID- 27694157
TI  - A Randomized Phase II Study of Linsitinib (OSI-906) Versus Topotecan in Patients
      With Relapsed Small-Cell Lung Cancer.
AB  - LESSONS LEARNED: Targeted therapy options for SCLC patients are limited; no
      agent, thus far, has resulted in a strategy promising enough to progress to phase
      III trials.Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase
      inhibitor, may be one agent with activity against SCLC.Despite lack of a reliable
      predictive biomarker in this disease, which may have partly contributed to the
      negative outcome reported here, linsitinib, although safe, showed no clinical
      activity in unselected, relapsed SCLC patients. BACKGROUND: Treatment of relapsed
      small-cell lung cancer (SCLC) remains suboptimal. Insulin growth factor-1
      receptor (IGF-1R) signaling plays a role in growth, survival, and chemoresistance
      in SCLC. Linsitinib is a potent IGF-1R tyrosine kinase inhibitor that potentially
      may be active against SCLC. METHODS: In this phase II study, 8 eligible patients
      were randomly assigned in a 1:2 ratio to topotecan (1.5 mg/m2 intravenously or
      2.3 mg/m2 orally, daily for 5 days for 4 cycles) or linsitinib (150 mg orally
      twice daily until progression). The primary endpoint was progression-free
      survival. Patients with relapsed SCLC, platinum sensitive or resistant,
      performance status (PS) 0-2, and adequate hematologic, renal, and hepatic
      function were enrolled. Patients with diabetes, cirrhosis, and those taking
      insulinotropic agents were excluded. Crossover to linsitinib was allowed at
      progression. RESULTS: Fifteen patients received topotecan (8 resistant, 3 with PS
      2) and 29 received linsitinib (16 resistant, 5 with PS 2). Two partial responses
      were observed with topotecan. Only 4 of 15 patients with topotecan and 1 of 29
      with linsitinib achieved stable disease. Median progression-free survival was 3.0
      (95% confidence interval [CI], 1.5-3.6) and 1.2 (95% CI, 1.1-1.4) months for
      topotecan and linsitinib, respectively (p = .0001). Median survival was 5.3 (95%
      CI, 2.2-7.6) and 3.4 (95% CI, 1.8-5.6) months for topotecan and linsitinib,
      respectively (p = .71). Grade 3/4 adverse events (>5% incidence) included anemia,
      thrombocytopenia, neutropenia/leukopenia, diarrhea, fatigue, dehydration, and
      hypokalemia for topotecan; and thrombocytopenia, fatigue, and alanine
      aminotransferase/aspartate aminotransferase elevations for linsitinib.
      CONCLUSION: Linsitinib was safe but showed no clinical activity in unselected,
      relapsed SCLC patients.

PMID- 27694158
TI  - MSF urges world leaders to act over bombing of hospitals in Aleppo.

PMID- 27694159
TI  - Low vaccination coverage of Greek Roma children amid economic crisis: national
      survey using stratified cluster sampling.
AB  - Background: Research on Roma health is fragmentary as major methodological
      obstacles often exist. Reliable estimates on vaccination coverage of Roma
      children at a national level and identification of risk factors for low coverage
      could play an instrumental role in developing evidence-based policies to promote
      vaccination in this marginalized population group. Methods: We carried out a
      national vaccination coverage survey of Roma children. Thirty Roma settlements,
      stratified by geographical region and settlement type, were included; 7-10
      children aged 24-77 months were selected from each settlement using systematic
      sampling. Information on children's vaccination coverage was collected from
      multiple sources. In the analysis we applied weights for each stratum, identified
      through a consensus process. Results: A total of 251 Roma children participated
      in the study. A vaccination document was presented for the large majority (86%).
      We found very low vaccination coverage for all vaccines. In 35-39% of children
      'minimum vaccination' (DTP3 and IPV2 and MMR1) was administered, while 34-38% had
      received HepB3 and 31-35% Hib3; no child was vaccinated against tuberculosis in
      the first year of life. Better living conditions and primary care services close
      to Roma settlements were associated with higher vaccination indices. Conclusions:
      Our study showed inadequate vaccination coverage of Roma children in Greece, much
      lower than that of the non-minority child population. This serious public health
      challenge should be systematically addressed, or, amid continuing economic
      recession, the gap may widen. Valid national estimates on important
      characteristics of the Roma population can contribute to planning inclusion
      policies.

PMID- 27694160
TI  - Cost analysis of a peer support programme for patients with type 2 diabetes: a
      secondary analysis of a controlled trial.
AB  - Background: This study aimed to explore if group-based peer support as an
      additional component to a disease management programme (DMP) in type 2 diabetes
      can reduce the number of prescribed drugs; hospital admissions; and length of
      hospital stay and therefore be a cost-effective model. Methods: Controlled study
      based on a secondary data analysis of a cluster randomized trial. Our study
      population was general practitioners and patients in the province of Salzburg.
      The 24-months intervention consisted of regular group meetings facilitated by
      trained peer supporters. The groups exercised together, discussed diabetes
      related topics, and received support by professionals. Data was anonymously
      collected on clusters through the statutory health insurance. Results: Data were
      available of 118 (82.5%,17 clusters of the patients in the original randomized
      trial) participants in the intervention and 143 (77.3%,19 clusters) in the
      control groups. The length of hospital stay was shorter in the intervention
      groups compared with controls. The mean difference during the 24-month study
      period was -40.13 days (95% CI - 78.54 to - 1.71, P = 0.041) in favour of the
      intervention groups. No differences were seen in the number of prescribed drugs
      and hospital admission. Estimated yearly savings by reducing the length of
      hospital stay was ?1660.60 per patient. Conclusion: A group-based peer support
      programme as an additional component of a DMP in type 2 diabetes is a promising
      approach to optimize diabetes care and to enhance lifestyle interventions in
      primary care. Peer support seems to reduce length of hospital stay and could
      therefore be a cost-effective model.

PMID- 27694162
TI  - Prostate Cancer Imaging and Therapy: Potential Role of Nanoparticles.
AB  - Over the last 2 decades, the use of nanoparticle imaging has been investigated
      extensively for both diagnosis and therapy of prostate cancer. This review
      discusses the various classes of nanoparticles currently in clinical use or at
      the advanced preclinical stage. In particular, we focus on the unique properties
      of nanoparticles, as a group, that make them suitable for imaging and therapy.
      The characteristics of each nanoparticle are detailed. Iron oxide nanoparticles,
      extensively used for MRI of prostate cancer, are discussed in depth.

PMID- 27694161
TI  - EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2-Mediated Renal Water
      Reabsorption.
AB  - Nephrogenic diabetes insipidus (NDI) is caused by impairment of vasopressin (VP)
      receptor type 2 signaling. Because potential therapies for NDI that target the
      canonical VP/cAMP/protein kinase A pathway have so far proven ineffective,
      alternative strategies for modulating aquaporin 2 (AQP2) trafficking have been
      sought. Successful identification of compounds by our high-throughput chemical
      screening assay prompted us to determine whether EGF receptor (EGFR) inhibitors
      stimulate AQP2 trafficking and reduce urine output. Erlotinib, a selective EGFR
      inhibitor, enhanced AQP2 apical membrane expression in collecting duct principal
      cells and reduced urine volume by 45% after 5 days of treatment in mice with
      lithium-induced NDI. Similar to VP, erlotinib increased exocytosis and decreased
      endocytosis in LLC-PK1 cells, resulting in a significant increase in AQP2
      membrane accumulation. Erlotinib increased phosphorylation of AQP2 at Ser-256 and
      Ser-269 and decreased phosphorylation at Ser-261 in a dose-dependent manner.
      However, unlike VP, the effect of erlotinib was independent of cAMP, cGMP, and
      protein kinase A. Conversely, EGF reduced VP-induced AQP2 Ser-256
      phosphorylation, suggesting crosstalk between VP and EGF in AQP2 trafficking and
      a role of EGF in water homeostasis. These results reveal a novel pathway that
      contributes to the regulation of AQP2-mediated water reabsorption and suggest new
      potential therapeutic strategies for NDI treatment.

PMID- 27694163
TI  - Evaluation of Prostate Cancer with PET/MRI.
AB  - In the ongoing effort to understand and cure prostate cancer, imaging modalities
      are constantly evolving to assist in clinical decisions. Multiparametric MRI can
      be used to direct prostate biopsies, improve diagnostic yield, and help
      clinicians make more accurate decisions. PET is superior in providing biologic
      information about the cancer and is sensitive and highly specific. Integrated
      PET/MRI is a welcome technical advance with great potential to influence the
      diagnosis and management of prostate cancer in clinical practice.

PMID- 27694164
TI  - Utility of Ultrasound in the Diagnosis, Treatment, and Follow-up of Prostate
      Cancer: State of the Art.
AB  - Prostate cancer screening currently consists of serum prostate-specific antigen
      and digital rectal examination, followed by transrectal ultrasound-guided biopsy
      for diagnostic confirmation. Although the current paradigm of prostate cancer
      screening has led to a decrease in advanced disease and cancer-related mortality,
      these techniques have limitations in terms of sensitivity and specificity,
      resulting in missed cancers that are clinically significant and the overdetection
      of clinically insignificant cancers. New imaging techniques and technologies are
      required to improve the detection of prostate cancer. This article summarizes the
      use of novel ultrasound techniques and technologies in the detection, biopsy, and
      treatment of prostate cancer.

PMID- 27694166
TI  - Radiotheranostics in Prostate Cancer: Introduction and Overview.

PMID- 27694165
TI  - Bone-Targeted Imaging and Radionuclide Therapy in Prostate Cancer.
AB  - Although selective metabolic and receptor-based molecular agents will surely be
      included in the future of prostate cancer diagnosis and therapy, currently
      available inorganic compounds-such as 18F-NaF for the diagnosis of bony disease
      and 223RaCl2 for the therapy of bone metastases-were recently shown to be
      superior to standard 99mTc-phosphonates for diagnosis and 153Sm
      ethylenediaminetetramethylene phosphonate or 89SrCl2 for therapy. The advantages
      of 18F-NaF include improved lesion detection and, when used in combination with
      CT, improved diagnostic confidence and specificity. In addition to being the
      first approved alpha-emitter, 223RaCl2 is the first radiopharmaceutical to show
      an increase in overall survival, a decrease in skeletal events, palliation of
      bone pain, and a low profile of adverse reactions (which are mild and
      manageable). The management of metastatic bone disease with 223RaCl2 is uniquely
      satisfying, as patients can be monitored directly during their monthly treatment
      visits.

PMID- 27694168
TI  - Evaluation of Prostate Cancer with 11C-Acetate PET/CT.
AB  - In this article, we will first describe the metabolic fate of 11C-acetate; then
      discuss its biodistribution in health and disease; and subsequently focus on its
      key clinical applications, the detection and localization of prostate cancer
      tissue in patients with primary or recurrent disease. Finally, we will discuss
      the potential role of 11C-acetate in the context of other prostate cancer imaging
      probes and non-radionuclide-based imaging approaches.

PMID- 27694167
TI  - PET of Glucose Metabolism and Cellular Proliferation in Prostate Cancer.
AB  - Imaging of the Warburg effect, which is the principal but not the sole cause for
      enhanced glucose metabolism in tumors, with PET and 18F-FDG has become the
      mainstay for the imaging evaluation of several cancers. Despite the seemingly
      prevalent notion that 18F-FDG PET may not be useful in prostate cancer,
      relatively limited evidence suggests that this imaging modality can be useful for
      the evaluation of the extent of metastatic disease and the assessment of the
      therapy response and prognosis in men with castration-resistant prostate cancer.
      Incidental high focal 18F-FDG uptake in the prostate gland, although generally
      rare, may also indicate occult prostate cancer that may need to be further
      scrutinized. In general, 18F-FDG PET is not useful for initial staging and is of
      limited utility in the clinical setting of biochemical failure after prior
      definitive therapy for primary cancer. Although more experience is needed, it
      appears that the imaging of cellular proliferation with PET and 3'-deoxy-3'-18F
      fluorothymidine or 2'-18F-fluoro-5-methyl-1-beta-d-arabinofuranosyluracil may
      also allow for targeted biopsy and localization for focal therapy of aggressive
      prostate tumors as well as assessment of the therapy response to various standard
      and novel treatment regimens in patients with metastatic disease.

PMID- 27694170
TI  - Molecular Imaging and Targeted Radionuclide Therapy of Prostate Cancer.

PMID- 27694169
TI  - Evaluation of Prostate Cancer with 11C- and 18F-Choline PET/CT: Diagnosis and
      Initial Staging.
AB  - Early diagnosis and adequate staging are crucial for the choice of adequate
      treatment in prostate cancer (PC). Morphologic and functional imaging modalities,
      such as CT and MRI, have had limited accuracy in the diagnosis and nodal staging
      of PC. Molecular PET/CT imaging with 11C- or 18F-choline-labeled derivatives is
      increasingly being used, but its role in the diagnosis and initial staging of PC
      is controversial because of limitations in sensitivity and specificity for the
      detection of primary PC. For T staging, functional MRI is superior to 11C- or 18F
      choline PET/CT. For N staging, 11C- or 18F-choline PET/CT can provide potentially
      useful information that may influence treatment planning. For the detection of
      bone metastases, 11C- or 18F-choline PET/CT has had promising results; however,
      in terms of cost-effectiveness, the routine use of 11C- or 18F-choline PET/CT is
      still debatable. 11C- or 18F-choline PET/CT might be used in high-risk PC before
      radiation treatment planning, potentially affecting this planning (e.g.,
      regarding dose escalation). This review provides an overview of the diagnostic
      accuracy and limitations of 11C- or 18F-choline PET/CT in the diagnosis and
      staging of PC.

PMID- 27694171
TI  - 11C- or 18F-Choline PET/CT for Imaging Evaluation of Biochemical Recurrence of
      Prostate Cancer.
AB  - Recurrence of prostate cancer is suspected when an increase in the prostate
      specific antigen level is detected after radical treatment; the recurrence could
      be local relapse, distant relapse, or both. Differentiation between the two
      patterns of relapse is critical for choosing the proper treatment strategy.
      Choline PET/CT could be of help in discriminating patients with local, lymph
      node, and bone recurrences, thus having an impact on patient management.

PMID- 27694172
TI  - Evaluation of Prostate Cancer with 11C-Choline PET/CT for Treatment Planning,
      Response Assessment, and Prognosis.
AB  - The aim of this review is to report on the value of 11C-choline PET imaging as a
      diagnostic procedure for metastasis-directed therapies. Furthermore, the role of
      11C-choline PET/CT as a diagnostic tool for monitoring castration-resistant
      prostate cancer patients treated with systematic therapy is assessed. Finally,
      the role of 11C-choline PET/CT in the prediction of survival in both castration
      resistant prostate cancer patients and hormone-naive patients is investigated.

PMID- 27694173
TI  - Evaluation of Prostate Cancer Bone Metastases with 18F-NaF and 18F-Fluorocholine
      PET/CT.
AB  - 18F-fluorocholine is a specific promising agent for imaging tumor cell
      proliferation, particularly in prostate cancer, using PET/CT. It is a beneficial
      tool in the early detection of marrow-based metastases because it excludes
      distant metastases and evaluates the response to hormone therapy. In addition,
      18F-fluorocholine has the potential to differentiate between degenerative and
      malignant osseous abnormalities because degenerative changes are not choline
      avid; however, the agent may accumulate in recent traumatic bony lesions. On the
      other hand, 18F-NaF PET/CT can indicate increased bone turnover and is generally
      used in the assessment of primary and secondary osseous malignancies, the
      evaluation of response to treatment, and the clarification of abnormalities on
      other imaging modalities or clinical data. 18F-NaF PET/CT is a highly sensitive
      method in the evaluation of bone metastases from prostate cancer, but it has
      problematic specificity, mainly because of tracer accumulation in degenerative
      and inflammatory bone diseases. In summary, 18F-NaF PET/CT is a highly sensitive
      method, but 18F-fluorocholine PET/CT can detect early bone marrow metastases and
      provide greater specificity in the detection of bone metastases in patients with
      prostate cancer. However, the difference seems not to be significant.

PMID- 27694174
TI  - Evaluation of Prostate Cancer with Radiolabeled Amino Acid Analogs.
AB  - Conventional imaging of prostate cancer has limitations related to the frequently
      indolent biology of the disease. PET is a functional imaging method that can
      exploit various aspects of tumor biology to enable greater detection of prostate
      cancer than can be provided by morphologic imaging alone. Radiotracers that are
      in use or under investigation for targeting salient features of prostate cancer
      include those directed to glucose, choline, acetate, prostate-specific membrane
      antigen, bombesin, and amino acids. The tumor imaging features of this last class
      of radiotracers mirror the upregulation of transmembrane amino acid transport
      that is necessary in carcinomas because of increased amino acid use for energy
      requirements and protein synthesis. Natural and synthetic amino acids
      radiolabeled for PET imaging have been investigated in prostate cancer patients.
      Early work with naturally occurring amino acid-derived radiotracers, such as l
      11C-methionine and l-1-11C-5-hydroxytryptophan, demonstrated promising results,
      including greater sensitivity than 18F-FDG for intraprostatic and extraprostatic
      cancer detection. However, limitations with naturally occurring amino acid
      derived compounds, including metabolism of the radiotracer itself, led to the
      development of synthetic amino acid radiotracers, which are not metabolized and
      therefore more accurately reflect transmembrane amino acid transport. Of the
      synthetic amino acid-derived PET radiotracers, anti-1-amino-3-18F
      fluorocyclobutane-1-carboxylic acid (18F-FACBC or 18F-fluciclovine) has undergone
      the most promising translation to human use, including the availability of
      simplified radiosynthesis. Several studies have indicated advantageous
      biodistribution in the abdomen and pelvis with little renal excretion and bladder
      activity-characteristics beneficial for prostate cancer imaging. Studies have
      demonstrated improved lesion detection and diagnostic performance of 18F
      fluciclovine in comparison with conventional imaging, especially for recurrent
      prostate cancer, although issues with nonspecific uptake limit the potential role
      of 18F-fluciclovine in the diagnosis of primary prostate cancer. Although work is
      ongoing, recently published intrapatient comparisons of 18F-fluciclovine with 11C
      choline reported higher overall diagnostic performance of the former, especially
      for the detection of disease relapse. This review is aimed at providing a
      detailed overview of amino acid-derived PET compounds that have been studied for
      use in prostate cancer imaging.

PMID- 27694175
TI  - Bombesin-Targeted PET of Prostate Cancer.
AB  - Imaging plays an important role in prostate cancer (PC), including accurate
      evaluation of the extent of disease, assessment of sites of recurrent disease,
      and monitoring of response to treatment. Molecular imaging techniques are among
      the novel developments related to the imaging of PC, and various SPECT and PET
      radiopharmaceuticals are now available in clinical trials or commercially. Here
      we describe the preclinical and clinical use of gastrin-releasing peptide
      receptors as targets for the imaging of PC, with a focus on the development of
      PET tracers for the imaging of gastrin-releasing peptide receptor-positive
      tumors.

PMID- 27694176
TI  - What Medical, Urologic, and Radiation Oncologists Want from Molecular Imaging of
      Prostate Cancer.
AB  - As molecular imaging better delineates the state of prostate cancer, clinical
      management will evolve. The currently licensed imaging modalities are limited by
      lack of specificity or sensitivity for the extent of cancer and for predicting
      outcome in response to therapy. Clinicians want molecular imaging that-by being
      more reliable in tailoring treatment and monitoring response for each patient
      will become a key facet of precision medicine, surgery, and radiation therapy.
      Identifying patients who are candidates for specific or novel treatments is
      important, but equally important is the finding that a given patient may not be a
      good candidate for single-modality therapy. This article presents prostate cancer
      scenarios in which managing clinicians would welcome molecular imaging
      innovations to help with decision making. The potential role of newer techniques
      that may help fill this wish list is discussed.

PMID- 27694177
TI  - Evaluation of Castration-Resistant Prostate Cancer with Androgen Receptor-Axis
      Imaging.
AB  - Castration-resistant prostate cancer (CRPC) is the lethal form of prostate
      cancer, and more than 26,000 men will die from this disease in 2016. The
      pathophysiology of CRPC is clearly multifactorial, but most often, androgen
      receptor (AR) upregulation is associated with its earliest beginnings and the AR
      increase is part of the multimolecular complex including downstream effector
      proteins linked to AR (AR-axis) responsible for rapid proliferation and malignant
      features of the malignant cell. In both animal models and patients, glycolysis
      (Warburg effect) is also an early manifestation of CRPC transformation. At
      Memorial Sloan Kettering Cancer Center, we have focused our energies on imaging
      studies of the AR-axis in CRPC, using 18F-FDG, 18F-16beta-fluoro-5alpha
      dihydrotestosterone (18F-FDHT), and a variety of radiolabeled antibodies
      targeting downstream effectors, such as prostate-specific membrane antigen
      (PSMA). Small-molecular-weight PSMA-targeting agents are not part of this review.
      In this review, we will focus on molecular imaging of the AR-axis in metastatic
      CRPC (mCRPC) and discuss our personal experience with these tracers. Our goal is
      to put these radiopharmaceuticals in the context of mCRPC biology and diagnosis
      (e.g., 18F-FDHT).

PMID- 27694178
TI  - The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer.
AB  - The prostate-specific membrane antigen (PSMA) has received increased
      consideration during the past few years as an excellent target for both imaging
      and therapy of prostate cancer. After many years of outstanding preclinical
      research, the first significant step forward in clinical use was achieved in 2008
      with the first human experience with the small-molecule PSMA inhibitors 123I-MIP
      1972 and 123I-MIP-1095. A clinical breakthrough followed in 2011 with 68Ga-PSMA
      11 for PET imaging and 131I-MIP-1095 for endoradiotherapy of metastatic prostate
      cancer. Since then, PET/CT with 68Ga-PSMA-11 has rapidly spread worldwide, and
      endoradiotherapy with PSMA ligands has been conducted at increasing numbers of
      centers. 68Ga-PSMA-11 is currently the subject of multicenter studies in
      different countries. Since 2013, 131I-related PSMA therapy has been replaced by
      177Lu-labeled ligands, such as PSMA-617, which is also the subject of multicenter
      studies. Alternative PSMA ligands for both imaging and therapy are available.
      Among them is 99mTc-MIP-1404, which has recently entered a phase 3 clinical
      trial. This article focuses on the highlights of the development and clinical
      application of PSMA ligands.

PMID- 27694180
TI  - PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate
      Cancer: The Bad Berka Experience Since 2013.
AB  - A potential milestone in personalized nuclear medicine is theranostics of
      metastatic castration-resistant prostate cancer (mCRPC) based on molecular
      imaging using PET/CT with 68Ga-labeled prostate-specific membrane antigen (PSMA)
      ligands and molecular radiotherapy using PSMA-targeted radioligand therapy (PRLT)
      with 177Lu-PSMA ligands. 68Ga-PSMA PET/CT enables accurate detection of mCRPC
      lesions with high diagnostic sensitivity and specificity and provides
      quantitative and reproducible data that can be used to select patients for PRLT
      and therapeutic monitoring. Our comprehensive experience over the last 3 years
      using different radioligands indicates that PRLT is highly effective for the
      treatment of mCRPC, even in advanced cases, and potentially lends a significant
      benefit to overall and progression-free survival. Additionally, significant
      improvement in clinical symptoms and excellent palliation of pain can be
      achieved.

PMID- 27694181
TI  - Captures of Boll Weevils (Coleoptera: Curculionidae) in Relation to Trap Distance
      From Cotton Fields.
AB  - The boll weevil (Anthonomus grandis grandis Boheman) has been eradicated from
      much of the United States, but remains an important pest of cotton (Gossypium
      spp.) in other parts of the Americas. Where the weevil occurs, the pheromone trap
      is a key tool for population monitoring or detection. Traditional monitoring
      programs have placed traps in or near the outermost cotton rows where damage by
      farm equipment can cause loss of trapping data. Recently, some programs have
      adopted a trap placement adjacent to but outside monitored fields. The effects of
      these changes have not been previously reported. Captures of early-season boll
      weevils by traps near (<=1 m) or far (7-10 m) from the outermost cotton row were
      evaluated. In 2005, during renewed efforts to eradicate the boll weevil from the
      Lower Rio Grande Valley of Texas, far traps consistently captured more weevils
      than traps near cotton. Traps at both placements indicated similar patterns of
      early-season weevil captures, which were consistent with those previously
      reported. In 2006, no distinction between trap placements was detected. Early
      season patterns of captures in 2006 were again similar for both trap placements,
      but captures were much lower and less regular compared with those observed in
      2005. These results suggest magnitude and likelihood of weevil capture in traps
      placed away from cotton are at least as high as for traps adjacent to cotton.
      Therefore, relocation of traps away from the outer rows of cotton should not
      negatively impact ability to monitor or detect the boll weevil.

PMID- 27694179
TI  - Prostate-Specific Membrane Antigen-Targeted Radiohalogenated PET and Therapeutic
      Agents for Prostate Cancer.
AB  - Radiohalogenated agents are often the first line of pursuit in the development of
      new radiopharmaceuticals-whether antibodies, peptides, or small molecules-because
      of their ease of synthesis, lack of substantial steric perturbation of the
      original affinity agent (in some cases, providing enhanced affinity), and
      capacity to be transformed into therapeutics (in some cases, with a mere switch
      of an isotope). They often provide proof of a principle before optimization for
      pharmacokinetics or generation of radiometallated agents, when the latter are
      necessary. In particular, 18F has been well integrated into normal clinical work
      flow in the form of 18F-FDG for oncologic imaging, with reliable daily production
      and distribution to sites for immediate use, without the need for on-site
      preparation. Here we discuss radiohalogenated versions of imaging and therapeutic
      agents targeting the prostate-specific membrane antigen (PSMA); these were among
      the first such agents to be synthesized and used clinically. PSMA is highly
      expressed on prostate cancer epithelial cells and is currently being extensively
      investigated around the world as a target for imaging and therapy of prostate
      cancer. Additionally, the presence of PSMA on nonprostate tumor neovasculature
      has opened the possibility of PSMA-targeted molecules as generalizable cancer
      imaging and therapy agents. We focus on 18F-labeled agents for PET, as they begin
      to redefine-along with the corresponding 68Ga-labeled agents discussed elsewhere
      in this supplement to The Journal of Nuclear Medicine-the management of prostate
      cancer across a variety of clinical contexts.

PMID- 27694182
TI  - Demographic Analysis of Sex Ratio on Population Growth of Bactrocera dorsalis
      (Diptera: Tephritidae) With Discussion of Control Efficacy Using Male
      Annihilation.
AB  - The life table data for the oriental fruit fly, Bactrocera dorsalis (Hendel), at
      different adult sex ratios (1?: 1?, 1?: 50?, 50?: 1? free-choice mating, and 50?:
      1? no-choice mating) were collected to determine the effects of sex-ratio
      manipulation on current pest control procedures. At 1?: 1?, females mated, on
      average, 2.3 times during their lifetime with a mean fecundity (F) of 1,122 eggs.
      The net reproductive rate (R0), intrinsic rate of increase (r), finite rate
      (lambda), and mean generation time (T) were 561.0 offspring, 0.1693 d- 1, 1.1844
      d- 1, and 37.4 d, respectively. At 50?: 1? free-choice mating, males mated 46.7
      times during their lifetime, while at 50?: 1? no-choice mating, males mated on
      average 50 times during their lifetime, and all females mating only once in both
      treatments. The values for F, r, and lambda were significantly lower for both
      50?: 1? treatments than those in the 1?: 1? group; the R0 values, however, were
      either equal to or even higher than those in the 1?: 1? treatment. In the male
      biased sex ratio (1?: 50?), fecundity was the highest (1,610 eggs) and female
      average life span the longest (166 d), while the R0 was the lowest (31.6
      offspring) among all treatments. Population projections showed that even at a sex
      ratio of 50?: 1?, B. dorsalis could still produce a large number of offspring.
      These findings demonstrate that management strategies for controlling B. dorsalis
      could be properly evaluated by using demographic methods. Because female
      annihilation appears to be a more effective control strategy, it should be
      considered as a viable alternative.

PMID- 27694183
TI  - Phytophagy by the Mullein Bug (Hemiptera: Miridae) on Apples: Feeding Behavior
      and Fruit Damage.
AB  - : The zoophytophagous mullein bug, Campylomma verbasci (Meyer-Dur) (Hemiptera:
      Miridae), is a beneficial predator of mites and aphids, but also a pest causing
      damage when it feeds on apples. The aim of this study was to evaluate three
      different parameters of phytophagy of the mullein bug both in laboratory
      (phytophagous behavior) and field (fruit damage) tests: 1) apple cultivar, 2)
      fruit size, and 3) nymphal instar. In the laboratory, nymphs were observed
      individually for 15 min in Petri dishes containing agar gel and an apple fruitlet
      to evaluate feeding punctures of four apple cultivars, four fruit sizes, and five
      nymphal instars. In the orchard, nymphs were caged at bloom in sleeve cages to
      evaluate damage on the developing fruit of seven apple cultivars and three
      nymphal instars on 'Red Delicious'. The feeding punctures in the laboratory were
      higher on 'Red Delicious' than on 'Honeycrisp'; fruit damage in the orchard did
      not differ among cultivars at mid-season, but was higher on 'Red Delicious' than
      on 'Lobo' and 'Marshall McIntosh' at harvest. The number of feeding punctures in
      the laboratory was higher on 7-9 mm than on 18-20 mm size fruit for 'Red
      Delicious', but not for 'Honeycrisp'. The number of feeding punctures in the
      laboratory made by the fifth nymphal instar was higher than those made by younger
      nymphs, but fruit damage in the orchard did not differ among nymphal instars. Our
      results will help to elaborate a management chart for this insect by minimizing
      risks and promoting its use for biocontrol. RESUME:  . : La punaise de la molene,
      Campylomma verbasci (Meyer-Dur) (Hemiptera: Miridae), est un predateur benefique
      zoophytophage des acariens et pucerons dans les vergers, mais egalement un
      ravageur causant des dommages lorsqu'il se nourrit sur les pommes. Le but de
      cette etude etait d'evaluer trois parametres differents sur la phytophagie de la
      punaise de la molene, a la fois en laboratoire (comportement phytophage) et sur
      le terrain (dommages aux fruits) : 1) les cultivars de pommes, 2) la taille des
      fruits, et 3) les stades larvaires. En laboratoire, les larves etaient observees
      individuellement pendant 15 min dans des boites de Petri contenant un gel d'agar
      et une jeune pomme afin de determiner les piqures de nutrition sur quatre
      cultivars de pommes, quatre tailles de fruit et cinq stades larvaires differents.
      En verger, des larves ont ete encagees a la floraison dans des manchons en
      mousseline afin d'evaluer les dommages sur les fruits en developpement. Les
      essais ont ete effectues sur sept cultivars de pommes ainsi qu'avec trois stades
      larvaires sur le cultivar "Delicieuse rouge". Les piqures de nutrition en
      laboratoire etaient plus nombreuses sur "Delicieuse rouge" que sur "Honeycrisp";
      les dommages aux fruits en verger ne differaient pas entre les cultivars a mi
      saison, mais etaient plus nombreux sur "Delicieuse rouge" que sur "Lobo" et
      "Marshall McIntosh" a la recolte. Les piqures de nutrition en laboratoire etaient
      plus nombreuses pour la taille de fruit 7-9 mm que 18-20 mm sur "Delicieuse
      rouge", mais pas sur "Honeycrisp". Le nombre de piqures de nutrition (en
      laboratoire) faites par les larves de stade 5 etaient plus nombreuses que celles
      faites par les larves plus jeunes, mais les dommages aux fruits (en verger) ne
      differaient pas entre les stades larvaires. Ces resultats vont aider a elaborer
      une charte de gestion de cet insecte en minimisant les risques et en favorisant
      son role d'agent de lutte biologique.

PMID- 27694185
TI  - The Influence of Nature Stimulus in Enhancing the Birth Experience.
AB  - The physical environment is one of the factors that affect women's experience of
      labor. The basics of the childbirth process have not changed since the beginning
      of human existence; however, the environment in which women today give birth has
      changed significantly. Incorporating design elements and strategies that calm and
      reduce negative emotions may create positive experiences for women in labor. The
      purpose of this study was to examine the impact of one such strategy, namely, the
      presentation of images of nature, on the labor and delivery experience. The study
      findings showed that the experimental condition has a higher score on the Quality
      of Care From the Patient's Perspective (QPP) subscale. In addition, there was an
      increase in the QPP scores associated with the increase in Nature TV watching
      time, QPP mean of watching time (less than 1 hr) group, m = 4.5 and QPP mean of
      watching time (more than 3 hs), m = 4.8. The mean score for the heart rate was
      lower in the experimental condition, m = 84.60, than in the control one, m =
      90.49. For Apgar, the mean score was higher for Group A, m = 8.65, and Group B, m
      = 8.92. These findings support the study hypothesis which states that the nature
      images would influence the labor experience positively. In addition, the findings
      emphasize the importance of incorporating nonpharmacological techniques in the
      labor and delivery room (LDR) units to sooth the pain. Adding nature imagery to
      the LDR environment can be one of these techniques.

PMID- 27694187
TI  - Basal cell carcinoma in two Hermann's tortoises (Testudo hermanni).
AB  - Neoplastic disorders are frequently encountered in the practice of reptile
      medicine. Herein we report the clinical behavior, antemortem diagnosis, and
      histopathologic characteristics of a recurrent intraoral keratinizing basal cell
      carcinoma (BCC) and a metastatic BCC of the carapace in 2 Hermann's tortoises
      (Testudo hermanni). Although squamous cell carcinomas (SCCs) in tortoises show
      similar predilection sites and gross pathologic features, the BCCs described in
      our report were characterized by a remarkably fast and highly infiltrative growth
      in comparison to SCCs. Accordingly, early diagnosis including reliable
      discrimination from SCC is essential toward the management of this neoplastic
      entity in tortoises.

PMID- 27694184
TI  - A Dominant Mutation in the HT1 Kinase Uncovers Roles of MAP Kinases and GHR1 in
      CO2-Induced Stomatal Closure.
AB  - Activation of the guard cell S-type anion channel SLAC1 is important for stomatal
      closure in response to diverse stimuli, including elevated CO2 The majority of
      known SLAC1 activation mechanisms depend on abscisic acid (ABA) signaling.
      Several lines of evidence point to a parallel ABA-independent mechanism of CO2
      induced stomatal regulation; however, molecular details of this pathway remain
      scarce. Here, we isolated a dominant mutation in the protein kinase HIGH LEAF
      TEMPERATURE1 (HT1), an essential regulator of stomatal CO2 responses, in an ozone
      sensitivity screen of Arabidopsis thaliana The mutation caused constitutively
      open stomata and impaired stomatal CO2 responses. We show that the mitogen
      activated protein kinases (MPKs) MPK4 and MPK12 can inhibit HT1 activity in vitro
      and this inhibition is decreased for the dominant allele of HT1. We also show
      that HT1 inhibits the activation of the SLAC1 anion channel by the protein
      kinases OPEN STOMATA1 and GUARD CELL HYDROGEN PEROXIDE-RESISTANT1 (GHR1) in
      Xenopus laevis oocytes. Notably, MPK12 can restore SLAC1 activation in the
      presence of HT1, but not in the presence of the dominant allele of HT1. Based on
      these data, we propose a model for sequential roles of MPK12, HT1, and GHR1 in
      the ABA-independent regulation of SLAC1 during CO2-induced stomatal closure.

PMID- 27694189
TI  - Successful percutaneous edge-to-edge repair in degenerative tricuspid valve
      regurgitation using the MitraClip system.

PMID- 27694188
TI  - Nucleotide sequence analysis of a DNA region involved in capsular polysaccharide
      biosynthesis reveals the molecular basis of the nontypeability of two
      Actinobacillus pleuropneumoniae isolates.
AB  - The aim of our study was to reveal the molecular basis of the serologic
      nontypeability of 2 Actinobacillus pleuropneumoniae field isolates. Nine field
      strains of A. pleuropneumoniae, the causative agent of porcine pleuropneumonia,
      were isolated from pigs raised on the same farm and sent to our diagnostic
      laboratory for serotyping. Seven of the 9 strains were identified as serovar 15
      strains by immunodiffusion tests. However, 2 strains, designated FH24-2 and FH24
      5, could not be serotyped with antiserum prepared against serovars 1-15. Strain
      FH24-5 showed positive results in 2 serovar 15-specific PCR tests, whereas strain
      FH24-2 was only positive in 1 of the 2 PCR tests. The nucleotide sequence
      analysis of gene clusters involved in capsular polysaccharide biosynthesis of the
      2 nontypeable strains revealed that both had been rendered nontypeable by the
      action of ISApl1, a transposable element of A. pleuropneumoniae belonging to the
      IS30 family. The results showed that ISApl1 of A. pleuropneumoniae can interfere
      with both the serologic and molecular typing methods, and that nucleotide
      sequence analysis across the capsular gene clusters is the best means of
      determining the cause of serologic nontypeability in A. pleuropneumoniae.

PMID- 27694190
TI  - Renal denervation: a blunt weapon against isolated systolic hypertension?

PMID- 27694191
TI  - Plasma concentration of serotonin is a novel biomarker for coronary microvascular
      dysfunction in patients with suspected angina and unobstructive coronary
      arteries.
AB  - Aims: Although the importance of coronary microvascular dysfunction (CMD) has
      been emerging, reliable biomarkers for CMD remain to be developed. We examined
      the potential usefulness of plasma concentration of serotonin to diagnose CMD in
      patients with suspected angina and unobstructive coronary arteries. Methods and
      results: We enrolled 198 consecutive patients (M/F 116/82, 60.2 +/- 13.3 years
      old) who underwent acetylcholine provocation test and measured plasma serotonin
      concentration. Coronary microvascular dysfunction was defined as myocardial
      lactate production without or prior to the occurrence of epicardial coronary
      spasm during acetylcholine provocation test. Although no statistical difference
      in plasma concentration of serotonin [median (inter-quartile range) nmol/L] was
      noted between the vasospastic angina (VSA) and non-VSA groups [6.8 (3.8, 10.9)
      vs. 5.1 (3.7, 8.4), P = 0.135], it was significantly higher in patients with CMD
      compared with those without it [7.7 (4.5, 14.2) vs. 5.6 (3.7, 9.3), P = 0.008].
      Among the four groups classified according to the presence or absence of VSA and
      CMD, serotonin concentration was highest in the VSA with CMD group. Importantly,
      there was a positive correlation between plasma serotonin concentration and
      baseline thrombolysis in myocardial infarction frame count (P = 0.001), a marker
      of coronary vascular resistance. The classification and regression trees analysis
      showed that plasma serotonin concentration of 9.55 nmol/L was the first
      discriminator to stratify the risk for the presence of CMD. In multivariable
      analysis, serotonin concentration greater than the cut-off value had the largest
      odds ratio in the prediction of CMD [odds ratio (95% confidence interval) 2.63
      (1.28-5.49), P = 0.009]. Conclusions: Plasma concentration of serotonin may be a
      novel biomarker for CMD in patients with angina and unobstructive coronary
      arteries.

PMID- 27694192
TI  - Yacoub procedure to treat giant pulmonary artery aneurysm.

PMID- 27694195
TI  - Combining multiple tools outperforms individual methods in gene set enrichment
      analyses.
AB  - Motivation: Gene set enrichment (GSE) analysis allows researchers to efficiently
      extract biological insight from long lists of differentially expressed genes by
      interrogating them at a systems level. In recent years, there has been a
      proliferation of GSE analysis methods and hence it has become increasingly
      difficult for researchers to select an optimal GSE tool based on their particular
      dataset. Moreover, the majority of GSE analysis methods do not allow researchers
      to simultaneously compare gene set level results between multiple experimental
      conditions. Results: The ensemble of genes set enrichment analyses (EGSEA) is a
      method developed for RNA-sequencing data that combines results from twelve
      algorithms and calculates collective gene set scores to improve the biological
      relevance of the highest ranked gene sets. EGSEA's gene set database contains
      around 25 000 gene sets from sixteen collections. It has multiple visualization
      capabilities that allow researchers to view gene sets at various levels of
      granularity. EGSEA has been tested on simulated data and on a number of human and
      mouse datasets and, based on biologists' feedback, consistently outperforms the
      individual tools that have been combined. Our evaluation demonstrates the
      superiority of the ensemble approach for GSE analysis, and its utility to
      effectively and efficiently extrapolate biological functions and potential
      involvement in disease processes from lists of differentially regulated genes.
      Availability and Implementation: EGSEA is available as an R package at
      http://www.bioconductor.org/packages/EGSEA/ . The gene sets collections are
      available in the R package EGSEAdata from
      http://www.bioconductor.org/packages/EGSEAdata/ . Contacts:
      monther.alhamdoosh@csl.com.au mritchie@wehi.edu.au. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 27694198
TI  - bTSSfinder: a novel tool for the prediction of promoters in cyanobacteria and
      Escherichia coli.
AB  - Motivation: The computational search for promoters in prokaryotes remains an
      attractive problem in bioinformatics. Despite the attention it has received for
      many years, the problem has not been addressed satisfactorily. In any bacterial
      genome, the transcription start site is chosen mostly by the sigma (sigma) factor
      proteins, which control the gene activation. The majority of published bacterial
      promoter prediction tools target sigma 70 promoters in Escherichia coli .
      Moreover, no sigma-specific classification of promoters is available for
      prokaryotes other than for E. coli . Results: Here, we introduce bTSSfinder, a
      novel tool that predicts putative promoters for five classes of sigma factors in
      Cyanobacteria (sigma A , sigma C , sigma H , sigma G and sigma F ) and for five
      classes of sigma factors in E. coli (sigma 70 , sigma 38 , sigma 32 , sigma 28
      and sigma 24 ). Comparing to currently available tools, bTSSfinder achieves
      higher accuracy (MCC = 0.86, F 1 -score = 0.93) compared to the next best tool
      with MCC = 0.59, F 1 -score = 0.79) and covers multiple classes of promoters.
      Availability and Implementation: bTSSfinder is available standalone and online at
      http://www.cbrc.kaust.edu.sa/btssfinder . Contacts:
      ilham.shahmuradov@kaust.edu.sa or vladimir.bajic@kaust.edu.sa. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 27694206
TI  - The Global Genome Biodiversity Network (GGBN) Data Standard specification.
AB  - Genomic samples of non-model organisms are becoming increasingly important in a
      broad range of studies from developmental biology, biodiversity analyses, to
      conservation. Genomic sample definition, description, quality, voucher
      information and metadata all need to be digitized and disseminated across
      scientific communities. This information needs to be concise and consistent in
      today's ever-increasing bioinformatic era, for complementary data aggregators to
      easily map databases to one another. In order to facilitate exchange of
      information on genomic samples and their derived data, the Global Genome
      Biodiversity Network (GGBN) Data Standard is intended to provide a platform based
      on a documented agreement to promote the efficient sharing and usage of genomic
      sample material and associated specimen information in a consistent way. The new
      data standard presented here build upon existing standards commonly used within
      the community extending them with the capability to exchange data on tissue,
      environmental and DNA sample as well as sequences. The GGBN Data Standard will
      reveal and democratize the hidden contents of biodiversity biobanks, for the
      convenience of everyone in the wider biobanking community. Technical tools exist
      for data providers to easily map their databases to the standard.Database URL:
      http://terms.tdwg.org/wiki/GGBN_Data_Standard.

PMID- 27694207
TI  - 3DFlu: database of sequence and structural variability of the influenza
      hemagglutinin at population scale.
AB  - The influenza virus type A (IVA) is an important pathogen which is able to cause
      annual epidemics and even pandemics. This fact is the consequence of the
      antigenic shifts and drifts capabilities of IVA, caused by the high mutation rate
      and the reassortment capabilities of the virus. The hemagglutinin (HA) protein
      constitutes the main IVA antigen and has a crucial role in the infection
      mechanism, being responsible for the recognition of host-specific sialic acid
      derivatives. Despite the relative abundance of HA sequence and serological
      studies, comparative structure-based analysis of HA are less investigated. The
      3DFlu database contains well annotated HA representatives: 1192 models and 263
      crystallographic structures. The relations between these proteins are defined
      using different metrics and are visualized as a network in the provided web
      interface. Moreover structural and sequence comparison of the proteins can be
      explored. Metadata information (e.g. protein identifier, IVA strain, year and
      location of infection) can enhance the exploration of the presented data. With
      our database researchers gain a useful tool for the exploration of high quality
      HA models, viewing and comparing changes in the HA viral subtypes at several
      information levels (sequence, structure, ESP). The complete and integrated view
      of those relations might be useful to determine the efficiency of transmission,
      pathogenicity and for the investigation of evolutionary tendencies of the
      influenza virus.Database URL: http://nucleus3d.cent.uw.edu.pl/influenza.

PMID- 27694208
TI  - ORDB, HORDE, ODORactor and other on-line knowledge resources of olfactory
      receptor-odorant interactions.
AB  - We present here an exploration of the evolution of three well-established, web
      based resources dedicated to the dissemination of information related to
      olfactory receptors (ORs) and their functional ligands, odorants. These resources
      are: the Olfactory Receptor Database (ORDB), the Human Olfactory Data Explorer
      (HORDE) and ODORactor. ORDB is a repository of genomic and proteomic information
      related to ORs and other chemosensory receptors, such as taste and pheromone
      receptors. Three companion databases closely integrated with ORDB are OdorDB,
      ORModelDB and OdorMapDB; these resources are part of the SenseLab suite of
      databases (http://senselab.med.yale.edu). HORDE
      (http://genome.weizmann.ac.il/horde/) is a semi-automatically populated database
      of the OR repertoires of human and several mammals. ODORactor
      (http://mdl.shsmu.edu.cn/ODORactor/) provides information related to OR-odorant
      interactions from the perspective of the odorant. All three resources are
      connected to each other via web-links.Database URL: http://senselab.med.yale.edu;
      http://genome.weizmann.ac.il/horde/; http://mdl.shsmu.edu.cn/ODORactor/.

PMID- 27694209
TI  - ASAP: a machine learning framework for local protein properties.
AB  - Determining residue-level protein properties, such as sites of post-translational
      modifications (PTMs), is vital to understanding protein function. Experimental
      methods are costly and time-consuming, while traditional rule-based computational
      methods fail to annotate sites lacking substantial similarity. Machine Learning
      (ML) methods are becoming fundamental in annotating unknown proteins and their
      heterogeneous properties. We present ASAP (Amino-acid Sequence Annotation
      Prediction), a universal ML framework for predicting residue-level properties.
      ASAP extracts numerous features from raw sequences, and supports easy integration
      of external features such as secondary structure, solvent accessibility,
      intrinsically disorder or PSSM profiles. Features are then used to train ML
      classifiers. ASAP can create new classifiers within minutes for a variety of
      tasks, including PTM prediction (e.g. cleavage sites by convertase, phosphoserine
      modification). We present a detailed case study for ASAP: CleavePred, an ASAP
      based model to predict protein precursor cleavage sites, with state-of-the-art
      results. Protein cleavage is a PTM shared by a wide variety of proteins sharing
      minimal sequence similarity. Current rule-based methods suffer from high false
      positive rates, making them suboptimal. The high performance of CleavePred makes
      it suitable for analyzing new proteomes at a genomic scale. The tool is
      attractive to protein design, mass spectrometry search engines and the discovery
      of new bioactive peptides from precursors. ASAP functions as a baseline approach
      for residue-level protein sequence prediction. CleavePred is freely accessible as
      a web-based application. Both ASAP and CleavePred are open-source with a flexible
      Python API.Database URL: ASAP's and CleavePred source code, webtool and tutorials
      are available at: https://github.com/ddofer/asap;
      http://protonet.cs.huji.ac.il/cleavepred.

PMID- 27694210
TI  - The BEL information extraction workflow (BELIEF): evaluation in the BioCreative V
      BEL and IAT track.
AB  - Network-based approaches have become extremely important in systems biology to
      achieve a better understanding of biological mechanisms. For network
      representation, the Biological Expression Language (BEL) is well designed to
      collate findings from the scientific literature into biological network models.
      To facilitate encoding and biocuration of such findings in BEL, a BEL Information
      Extraction Workflow (BELIEF) was developed. BELIEF provides a web-based curation
      interface, the BELIEF Dashboard, that incorporates text mining techniques to
      support the biocurator in the generation of BEL networks. The underlying UIMA
      based text mining pipeline (BELIEF Pipeline) uses several named entity
      recognition processes and relationship extraction methods to detect concepts and
      BEL relationships in literature. The BELIEF Dashboard allows easy curation of the
      automatically generated BEL statements and their context annotations. Resulting
      BEL statements and their context annotations can be syntactically and
      semantically verified to ensure consistency in the BEL network. In summary, the
      workflow supports experts in different stages of systems biology network
      building. Based on the BioCreative V BEL track evaluation, we show that the
      BELIEF Pipeline automatically extracts relationships with an F-score of 36.4% and
      fully correct statements can be obtained with an F-score of 30.8%. Participation
      in the BioCreative V Interactive task (IAT) track with BELIEF revealed a systems
      usability scale (SUS) of 67. Considering the complexity of the task for new users
      learning BEL, working with a completely new interface, and performing complex
      curation-a score so close to the overall SUS average highlights the usability of
      BELIEF.Database URL: BELIEF is available at http://www.scaiview.com/belief/.

PMID- 27694212
TI  - Professionals' perspectives towards health promotion in residential aged care: an
      explorative study in Austria.
AB  - Following the trend in most developed countries, in Austria the oldest old are
      the fastest growing population group. Among this group, there is a high
      prevalence of multimorbidity, functional impairment, dementia and psychiatric
      conditions. While health promotion (HP) has been considered relevant in coping
      with the challenges of an aging population, it has so far been viewed as a
      foreign concept in relation to the oldest old, especially those living in
      residential aged care (RAC) facilities. Although there is an acknowledgement that
      HP should be integrated into routine nursing, there has been little research on
      how professionals working with RAC interpret and implement HP. In this study, 13
      semi-structured interviews were carried out with professionals from four major
      Austrian RAC providers. The data were analysed using thematic analysis. The
      findings show that, typically, professionals understand HP as a concept that is
      oriented towards maintaining potentials and resources, thereby promoting self
      determination, autonomy and social integration, including frail and functionally
      impaired elderly residents. However, data analysis also revealed a gap between
      the conceptual understanding and positive attitudes towards HP and its
      implementation in practice. Implementation of HP seems to occur in isolated
      cases, related to specific health issues. It seems that more complex HP
      approaches, especially the 'settings approach', are hardly practiced. To
      implement more comprehensive and systematic HP in Austrian RAC, support from
      external HP agencies as well as changes in financial incentives are needed.

PMID- 27694211
TI  - Ligand-induced growth and compaction of CD36 nanoclusters enriched in Fyn induces
      Fyn signaling.
AB  - Nanoclustering is an emerging organizational principle for membrane-associated
      proteins. The functional consequences of nanoclustering for receptor signaling
      remain largely unknown. Here, we applied quantitative multi-channel high- and
      super-resolution imaging to analyze the endothelial cell surface receptor CD36,
      the clustering of which upon binding to multivalent ligands, such as the anti
      angiogenic factor thrombospondin-1 (TSP-1), is thought to be crucial for
      signaling. We found that a substantial fraction of unligated CD36 exists in
      nanoclusters, which not only promote TSP-1 binding but are also enriched with the
      downstream effector Fyn. Exposure to multivalent ligands (TSP-1 or anti-CD36 IgM)
      that result in larger and denser CD36 clusters activates Fyn. Conversely,
      pharmacological perturbations that prevent the enhancement of CD36 clustering by
      TSP-1 abrogate Fyn activation. In both cases, there is no detectable change in
      Fyn enrichment at CD36 nanoclusters. These observations reveal a crucial role for
      the basal organization of a receptor into nanoclusters that are enriched with the
      signal-transducing downstream effectors of that receptor, such that enhancement
      of clustering by multivalent ligands is necessary and sufficient to activate the
      downstream effector without the need for its de novo recruitment.

PMID- 27694213
TI  - Effects of various types of anesthesia on hemodynamics, cardiac function, and
      glucose and lipid metabolism in rats.
AB  - Anesthesia can affect respiratory, circulatory, and endocrine systems but is
      necessary for certain experimental procedures such as echocardiography and blood
      sampling in small animals. We have now investigated the effects of four types of
      anesthesia [pentobarbital sodium (PENT), ketamine-xylazine (K/X), and low- or
      high-dose isoflurane (ISO)] on hemodynamics, cardiac function, and glucose and
      lipid metabolism in Sprague-Dawley rats. Aortic pressure, heart rate, and
      echocardiographic parameters were measured at various time points up to 45 min
      after the induction of anesthesia, and blood was then collected for measurement
      of parameters of glucose and lipid metabolism. Systolic aortic pressure remained
      constant in the PENT group, whereas it showed a biphasic pattern in the K/X group
      and a gradual decline in the ISO groups. Marked bradycardia was observed in the
      K/X group. The serum glucose concentration was increased and the plasma insulin
      level was reduced in the K/X and ISO groups compared with the PENT group. The
      concentrations of free fatty acids and norepinephrine in plasma were increased in
      the K/X group. Despite the metabolic effects of K/X and ISO, our results suggest
      that the marked bradycardic effect of K-X renders this combination appropriate
      for measurement of Doppler-derived indexes of left ventricular diastolic
      function, whereas the relative ease with which the depth of anesthesia can be
      controlled with ISO makes it suitable for manipulations or data collection over
      long time periods. On the other hand, PENT may be best suited for experiments
      that focus on measurement of cardiac function by M-mode echocardiography and
      metabolic parameters.

PMID- 27694214
TI  - Dyssynchronous calcium removal in heart failure-induced atrial remodeling.
AB  - We tested the hypothesis that in atrial myocytes from a rabbit left ventricular
      heart failure (HF) model, spatial inhomogeneity and temporal dyssynchrony of Ca
      removal during excitation-contraction coupling together with increased Na/Ca
      exchange (NCX) activity generate a substrate for proarrhythmic Ca release. Ca
      removal occurs via Ca reuptake into the sarcoplasmic reticulum and extrusion via
      NCX exclusively in the cell periphery since rabbit atrial myocytes lack
      transverse tubules. Ca removal kinetics were assessed by the time constant tau of
      decay of local peripheral subsarcolemmal (SS) and central (CT) action potential
      (AP)-induced Ca transients (CaTs) recorded in confocal line scan mode (using Fluo
      4). Spatial and temporal dyssynchrony of Ca removal was quantified by CV TAU,
      defined as the standard deviation of local tau along the transverse cell axis
      divided by mean tau. In normal cells CT CaT decline was slower compared with the
      SS domain, while in HF cells decline was accelerated, became equal in SS and CT
      regions, and a significant increase of CV TAU indicated an increased Ca removal
      dyssynchrony. In HF atrial cells NCX upregulation was accompanied by an overall
      higher incidence of spontaneous Ca waves and a higher propensity of
      arrhythmogenic Ca waves, defined as waves that triggered APs due to NCX-mediated
      membrane depolarization. NCX inhibition normalized CV TAU in HF atrial cells and
      decreased the propensity of Ca waves. In summary, HF atrial myocytes show
      accelerated but dyssynchronous diastolic Ca removal and altered sarcoplasmic
      reticulum Ca-ATPase (SERCA) and NCX activity that result in increased
      susceptibility to arrhythmia.

PMID- 27694216
TI  - Dietary nitrate supplementation attenuates the reduction in exercise tolerance
      following blood donation.
AB  - We tested the hypothesis that dietary nitrate (NO3-)-rich beetroot juice (BR)
      supplementation could partially offset deteriorations in O2 transport and
      utilization and exercise tolerance after blood donation. Twenty-two healthy
      volunteers performed moderate-intensity and ramp incremental cycle exercise tests
      prior to and following withdrawal of ~450 ml of whole blood. Before donation, all
      subjects consumed seven 70-ml shots of NO3--depleted BR [placebo (PL)] in the 48
      h preceding the exercise tests. During the 48 h after blood donation, subjects
      consumed seven shots of BR (each containing 6.2 mmol of NO3-, n = 11) or PL (n =
      11) before repeating the exercise tests. Hemoglobin concentration and hematocrit
      were reduced by ~8-9% following blood donation (P < 0.05), with no difference
      between the BR and PL groups. Steady-state O2 uptake during moderate-intensity
      exercise was ~4% lower after than before donation in the BR group (P < 0.05) but
      was unchanged in the PL group. The ramp test peak power decreased from
      predonation (341 +/- 70 and 331 +/- 68 W in PL and BR, respectively) to
      postdonation (324 +/- 69 and 322 +/- 66 W in PL and BR, respectively) in both
      groups (P < 0.05). However, the decrement in performance was significantly less
      in the BR than PL group (2.7% vs. 5.0%, P < 0.05). NO3- supplementation reduced
      the O2 cost of moderate-intensity exercise and attenuated the decline in ramp
      incremental exercise performance following blood donation. These results have
      implications for improving functional capacity following blood loss.

PMID- 27694215
TI  - Physiological and hypoxic oxygen concentration differentially regulates human c
      Kit+ cardiac stem cell proliferation and migration.
AB  - Cardiac stem cells (CSCs) are being evaluated for their efficacy in the treatment
      of heart failure. However, numerous factors impair the exogenously delivered
      cells' regenerative capabilities. Hypoxia is one stress that contributes to
      inadequate tissue repair. Here, we tested the hypothesis that hypoxia impairs
      cell proliferation, survival, and migration of human CSCs relative to
      physiological and room air oxygen concentrations. Human endomyocardial biopsy
      derived CSCs were isolated, selected for c-Kit expression, and expanded in vitro
      at room air (21% O2). To assess the effect on proliferation, survival, and
      migration, CSCs were transferred to physiological (5%) or hypoxic (0.5%) O2
      concentrations. Physiological O2 levels increased proliferation (P < 0.05) but
      did not affect survival of CSCs. Although similar growth rates were observed in
      room air and hypoxia, a significant reduction of beta-galactosidase activity (
      4,203 fluorescent units, P < 0.05), p16 protein expression (0.58-fold, P <
      0.001), and mitochondrial content (0.18-fold, P < 0.001) in hypoxia suggests that
      transition from high (21%) to low (0.5%) O2 reduces senescence and promotes
      quiescence. Furthermore, physiological O2 levels increased migration (P < 0.05)
      compared with room air and hypoxia, and treatment with mesenchymal stem cell
      conditioned media rescued CSC migration under hypoxia to levels comparable to
      physiological O2 migration (2-fold, P < 0.05 relative to CSC media control). Our
      finding that physiological O2 concentration is optimal for in vitro parameters of
      CSC biology suggests that standard room air may diminish cell regenerative
      potential. This study provides novel insights into the modulatory effects of O2
      concentration on CSC biology and has important implications for refining stem
      cell therapies.

PMID- 27694217
TI  - Carboxy-terminal deletion of the HDL receptor reduces receptor levels in liver
      and steroidogenic tissues, induces hypercholesterolemia, and causes fatal heart
      disease.
AB  - The HDL receptor SR-BI mediates the transfer of cholesteryl esters from HDL to
      cells and controls HDL abundance and structure. Depending on the genetic
      background, loss of SR-BI causes hypercholesterolemia, anemia, reticulocytosis,
      splenomegaly, thrombocytopenia, female infertility, and fatal coronary heart
      disease (CHD). The carboxy terminus of SR-BI (505QEAKL509) must bind to the
      cytoplasmic adaptor PDZK1 for normal hepatic-but not steroidogenic cell
      expression of SR-BI protein. To determine whether SR-BI's carboxy terminus is
      also required for normal protein levels in steroidogenic cells, we introduced
      into SR-BI's gene a 507Ala/STOP mutation that produces a truncated receptor (SR
      BIDeltaCT). As expected, the dramatic reduction of hepatic receptor protein in SR
      BIDeltaCT mice was similar to that in PDZK1 knockout (KO) mice. Unlike SR-BI KO
      females, SR-BIDeltaCT females were fertile. The severity of SR-BIDeltaCT mice's
      hypercholesterolemia was intermediate between those of SR-BI KO and PDZK1 KO
      mice. Substantially reduced levels of the receptor in adrenal cortical cells,
      ovarian cells, and testicular Leydig cells in SR-BIDeltaCT mice suggested that
      steroidogenic cells have an adaptor(s) functionally analogous to hepatic PDZK1.
      When SR-BIDeltaCT mice were crossed with apolipoprotein E KO mice (SR
      BIDeltaCT/apoE KO), pathologies including hypercholesterolemia, macrocytic
      anemia, hepatic and splenic extramedullary hematopoiesis, massive splenomegaly,
      reticulocytosis, thrombocytopenia, and rapid-onset and fatal occlusive coronary
      arterial atherosclerosis and CHD (median age of death: 9 wk) were observed. These
      results provide new insights into the control of SR-BI in steroidogenic cells and
      establish SR-BIDeltaCT/apoE KO mice as a new animal model for the study of CHD.

PMID- 27694218
TI  - Exercise-induced brachial artery blood flow and vascular function is impaired in
      systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a rare autoimmune disease characterized by
      debilitating fibrosis and vascular dysfunction; however, little is known about
      the circulatory response to exercise in this population. Therefore, we examined
      the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10
      patients with SSc (61 +/- 4 yr) and 15 age-matched healthy controls (56 +/- 5
      yr). Brachial artery diameter, blood flow, and mean arterial pressure (MAP) were
      determined at rest and during progressive static-intermittent handgrip exercise.
      Patients with SSc and controls were similar in body stature, handgrip strength,
      and MAP; however, brachial artery blood flow at rest was nearly twofold lower in
      patients with SSc compared with controls (22 +/- 4 vs. 42 +/- 5 ml/min,
      respectively; P < 0.05). Additionally, SSc patients had an ~18% smaller brachial
      artery lumen diameter with an ~28% thicker arterial wall at rest (P < 0.05).
      Although, during handgrip exercise, there were no differences in MAP between the
      groups, exercise-induced hyperemia and therefore vascular conductance were ~35%
      lower at all exercise workloads in patients with SSc (P < 0.05). Brachial artery
      vasodilation, as assessed by the relationship between Deltabrachial artery
      diameter and Deltashear rate, was significantly attenuated in the patients with
      SSc (P < 0.05). Finally, vascular dysfunction in the patients with SSc was
      accompanied by elevated blood markers of oxidative stress and attenuated
      endogenous antioxidant activity (P < 0.05). Together, these findings reveal
      attenuated exercise-induced brachial artery blood flow and conduit arterial
      vasodilatory dysfunction during handgrip exercise in SSc and suggest that
      elevated oxidative stress may play a role.

PMID- 27694221
TI  - New gene editing technique CRISPR-Cas9 raises important ethical questions, says
      advisory body.

PMID- 27694220
TI  - Exposure to cigarette smoke abrogates the beneficial effect of ischemic
      postconditioning.
AB  - Cigarette smoking is one of the risk factors for coronary artery disease.
      Although conditioning decreases infarct size in hearts from healthy animals,
      comorbidities may render it ineffective. We investigated the effects of cigarette
      smoke (CS) exposure on intracellular myocardial signaling, infarct size after
      ischemia-reperfusion, and the potential interference with ischemic conditioning.
      Exposure of mice to CS increased blood pressure, caused cardiac hypertrophy, and
      upregulated the nitric oxide synthatse (NOS)/soluble guanylate cyclase (sGC)/cGMP
      pathway. To test the effect of CS exposure on the endogenous cardioprotective
      mechanisms, mice were subjected to regional myocardial ischemia and reperfusion
      with no further intervention or application of preconditioning (PreC) or
      postconditioning (PostC). Exposure to CS did not increase the infarction compared
      with the room air (RA)-exposed group. PreC was beneficial for both CS and RA vs.
      nonconditioned animals. PostC was effective only in RA animals, while the infarct
      size-limiting effect was not preserved in the CS group. Differences in oxidative
      stress markers, Akt, and endothelial NOS phosphorylation and cGMP levels were
      observed between RA and CS groups subjected to PostC. In conclusion, exposure to
      CS does not per se increase infarct size. The beneficial effect of ischemic PreC
      is preserved in mice exposed to CS, as it does not affect the cardioprotective
      signaling; in contrast, PostC fails to protect CS-exposed mice due to impaired
      activation of the Akt/eNOS/cGMP axis that occurs in parallel to enhanced
      oxidative stress.

PMID- 27694222
TI  - Why do we shine lights in the eyes of conscious patients after head injury?

PMID- 27694219
TI  - FOXO3a regulates BNIP3 and modulates mitochondrial calcium, dynamics, and
      function in cardiac stress.
AB  - The forkhead box O3a (FOXO3a) transcription factor has been shown to regulate
      glucose metabolism, muscle atrophy, and cell death in postmitotic cells. Its role
      in regulation of mitochondrial and myocardial function is not well studied. Based
      on previous work, we hypothesized that FOXO3a, through BCL2/adenovirus E1B 19-kDa
      protein-interacting protein 3 (BNIP3), modulates mitochondrial morphology and
      function in heart failure (HF). We modulated the FOXO3a-BNIP3 pathway in normal
      and phenylephrine (PE)-stressed adult cardiomyocytes (ACM) in vitro and developed
      a cardiotropic adeno-associated virus serotype 9 encoding dominant-negative
      FOXO3a (AAV9.dn-FX3a) for gene delivery in a rat model of HF with preserved
      ejection fraction (HFpEF). We found that FOXO3a upregulates BNIP3 expression in
      normal and PE-stressed ACM, with subsequent increases in mitochondrial Ca2+,
      leading to decreased mitochondrial membrane potential, mitochondrial
      fragmentation, and apoptosis. Whereas dn-FX3a attenuated the increase in BNIP3
      expression and its consequences in PE-stressed ACM, AAV9.dn-FX3a delivery in an
      experimental model of HFpEF decreased BNIP3 expression, reversed adverse left
      ventricular remodeling, and improved left ventricular systolic and, particularly,
      diastolic function, with improvements in mitochondrial structure and function.
      Moreover, AAV9.dn-FX3a restored phospholamban phosphorylation at S16 and enhanced
      dynamin-related protein 1 phosphorylation at S637. Furthermore, FOXO3a
      upregulates maladaptive genes involved in mitochondrial apoptosis, autophagy, and
      cardiac atrophy. We conclude that FOXO3a activation in cardiac stress is
      maladaptive, in that it modulates Ca2+ cycling, Ca2+ homeostasis, and
      mitochondrial dynamics and function. Our results suggest an important role of
      FOXO3a in HF, making it an attractive potential therapeutic target.

PMID- 27694223
TI  - Sequential analysis of soil factors related to common scab of potatoes.
AB  - The severity of common scab (CS) of potatoes has been correlated with multiple
      environmental factors. This study aimed at separating the effect of factors
      related to local conditions from those correlated to the disease development at
      all studied sites using a mathematical adjustment of the variables' means for
      site and field. The experiment was conducted at two sites differing in soil
      conditions, where a field with low disease severity occurs next to one with high
      severity. Three cultivars susceptible to CS were grown in four replicates on each
      field. Bacteria, actinobacteria and the txtB gene, involved in the biosynthesis
      of the main CS pathogenicity factor, thaxtomin, were quantified by real-time PCR.
      Bulk soil, tuberosphere soil and potato periderm were characterized by carbon,
      nitrogen, phosphorus, sulfur, calcium, magnesium and iron contents. The
      adjustment of the data for field effects eliminated the confounding local
      conditions and showed that at all fields the CS severity was negatively
      correlated with soil S content while the number of txtB gene copies was
      positively correlated with soil C and N contents. Thus, those factors might have
      a more general relationship to the pathogen occurrence and disease severity,
      which needs to be verified in other environmental conditions.

PMID- 27694226
TI  - Pharmacokinetics and Differential Regulation of Cytochrome P450 Enzymes in Type 1
      Allergic Mice.
AB  - Type 1 allergic diseases are characterized by elevated production of specific
      immunoglobulin E (IgE) for each antigen and have become a significant health
      problem worldwide. This study investigated the effect of IgE-mediated allergy on
      drug pharmacokinetics. To further understand differential suppression of hepatic
      cytochrome P450 (P450) activity, we examined the inhibitory effect of nitric
      oxide (NO), a marker of allergic conditions. Seven days after primary
      sensitization (PS7) or secondary sensitization (SS7), hepatic CYP1A2, CYP2C,
      CYP2E1, and CYP3A activities were decreased to 45%-75% of the corresponding
      control; however, CYP2D activity was not downregulated. PS7 and SS7 did not
      change the expression levels of five P450 proteins. Disappearance of CYP1A2 and
      CYP2D substrates from the plasma was not significantly different between allergic
      mice and control mice. In contrast, the area under the curve of a CYP1A2-mediated
      metabolite in PS7 and SS7 mice was reduced by 50% of control values. Total
      clearances of a CYP2E1 substrate in PS7 and SS7 mice were significantly decreased
      to 70% and 50% respectively, of the control without altering plasma protein
      binding. Hepatic amounts of CYP1A2 and CYP2E1 substrates were enhanced by
      allergic induction, being responsible for each downregulated activity. NO
      scavenger treatment completely improved the downregulated P450 activities.
      Therefore, our data suggest that the onset of IgE-mediated allergy alters the
      pharmacokinetics of major P450-metabolic capacity-limited drugs except for CYP2D
      drugs. NO is highly expected to participate in regulatory mechanisms of the four
      P450 isoforms.

PMID- 27694227
TI  - Validity and reliability of the South African health promoting schools monitoring
      questionnaire.
AB  - Health promoting schools, as conceptualised by the World Health Organisation,
      have been developed in many countries to facilitate the health-education link. In
      1994, the concept of health promoting schools was introduced in South Africa. In
      the process of becoming a health promoting school, it is important for schools to
      monitor and evaluate changes and developments taking place. The Health Promoting
      Schools (HPS) Monitoring Questionnaire was developed to obtain opinions of
      students about their school as a health promoting school. It comprises 138
      questions in seven sections: socio-demographic information; General health
      promotion programmes; health related Skills and knowledge; Policies; Environment;
      Community-school links; and support Services. This paper reports on the
      reliability and face validity of the HPS Monitoring Questionnaire. Seven experts
      reviewed the questionnaire and agreed that it has satisfactory face validity. A
      test-retest reliability study was conducted with 83 students in three high
      schools in Cape Town, South Africa. The kappa-coefficients demonstrate mostly
      fair (kappa-scores between 0.21 and 0.4) to moderate (kappa-scores between 0.41
      and 0.6) agreement between test-retest General and Environment items; poor (kappa
      scores up to 0.2) agreement between Skills and Community test-retest items, fair
      agreement between Policies items, and for most of the questions focussing on
      Services a fair agreement was found. The study is a first effort at providing a
      tool that may be used to monitor and evaluate students' opinions about changes in
      health promoting schools. Although the HPS Monitoring Questionnaire has face
      validity, the results of the reliability testing were inconclusive. Further
      research is warranted.

PMID- 27694228
TI  - Equity-focused health impact assessment of Portuguese tobacco control
      legislation.
AB  - The World Health Organization recommend the Equity-Focused Health Impact
      Assessment (HIA) as a means to assess the impact of social and economic policies
      on the health of populations, and acknowledges their contribution to health
      inequality. We describe the application of the Equity-focused Impact Assessment
      methodology on the Portuguese law on Smoking Prevention and Tobacco Control (Law
      No. 37/2007). A rapid assessment was carried out to issue recommendations which
      could be incorporated into the law during a revision in 2014. Quantitative
      (consumption and health status indicators; equity analysis) and qualitative
      (Focus Group) approaches were taken to evaluate the impact of the law and
      formulate recommendations. Young people, men and women of low socioeconomic
      status, and pregnant women were identified as requiring specific and appropriate
      interventions to prevent smoking and support smoking cessation.

PMID- 27694229
TI  - Phosphinothricin Acetyltransferases Identified Using In Vivo, In Vitro, and
      Bioinformatic Analyses.
AB  - Acetylation of small molecules is widespread in nature, and in some cases, cells
      use this process to detoxify harmful chemicals. Streptomyces species utilize a
      Gcn5 N-acetyltransferase (GNAT), known as Bar, to acetylate and detoxify a self
      produced toxin, phosphinothricin (PPT), a glutamate analogue. Bar homologues,
      such as MddA from Salmonella enterica, acetylate methionine analogues such as
      methionine sulfoximine (MSX) and methionine sulfone (MSO), but not PPT, even
      though Bar homologues are annotated as PPT acetyltransferases. S. enterica was
      used as a heterologous host to determine whether or not putative PPT
      acetyltransferases from various sources could acetylate PPT, MSX, and MSO. In
      vitro and in vivo analyses identified substrates acetylated by putative PPT
      acetyltransferases from Deinococcus radiodurans (DR_1057 and DR_1182) and
      Geobacillus kaustophilus (GK0593 and GK2920). In vivo, synthesis of DR_1182,
      GK0593, and GK2920 blocked the inhibitory effects of PPT, MSX, and MSO. In
      contrast, DR_1057 did not detoxify any of the above substrates. Results of in
      vitro studies were consistent with the in vivo results. In addition, phylogenetic
      analyses were used to predict the functionality of annotated PPT
      acetyltransferases in Burkholderia xenovorans, Bacillus subtilis, Staphylococcus
      aureus, Acinetobacter baylyi, and Escherichia coli IMPORTANCE: The work reported
      here provides an example of the use of a heterologous system for the
      identification of enzyme function. Many members of this superfamily of proteins
      do not have a known function, or it has been annotated solely on the basis of
      sequence homology to previously characterized enzymes. The critical role of Gcn5
      N-acetyltransferases (GNATs) in the modulation of central metabolic processes,
      and in controlling metabolic stress, necessitates approaches that can reveal
      their physiological role. The combination of in vivo, in vitro, and
      bioinformatics approaches reported here identified GNATs that can acetylate and
      detoxify phosphinothricin.

PMID- 27694230
TI  - Interactions of Plutonium with Pseudomonas sp. Strain EPS-1W and Its
      Extracellular Polymeric Substances.
AB  - : Safe and effective nuclear waste disposal, as well as accidental radionuclide
      releases, necessitates our understanding of the fate of radionuclides in the
      environment, including their interaction with microorganisms. We examined the
      sorption of Pu(IV) and Pu(V) to Pseudomonas sp. strain EPS-1W, an aerobic
      bacterium isolated from plutonium (Pu)-contaminated groundwater collected in the
      United States at the Nevada National Security Site (NNSS) in Nevada. We compared
      Pu sorption to cells with and without bound extracellular polymeric substances
      (EPS). Wild-type cells with intact EPS sorbed Pu(V) more effectively than cells
      with EPS removed. In contrast, cells with and without EPS showed the same
      sorption affinity for Pu(IV). In vitro experiments with extracted EPS revealed
      rapid reduction of Pu(V) to Pu(IV). Transmission electron microscopy indicated
      that 2- to 3-nm nanocrystalline Pu(IV)O2 formed on cells equilibrated with high
      concentrations of Pu(IV) but not Pu(V). Thus, EPS, while facilitating Pu(V)
      reduction, inhibit the formation of nanocrystalline Pu(IV) precipitates.
      IMPORTANCE: Our results indicate that EPS are an effective reductant for Pu(V)
      and sorbent for Pu(IV) and may impact Pu redox cycling and mobility in the
      environment. Additionally, the resulting Pu morphology associated with EPS will
      depend on the concentration and initial Pu oxidation state. While our results are
      not directly applicable to the Pu transport situation at the NNSS, the results
      suggest that, in general, stationary microorganisms and biofilms will tend to
      limit the migration of Pu and provide an important Pu retardation mechanism in
      the environment. In a broader sense, our results, along with a growing body of
      literature, highlight the important role of microorganisms as producers of redox
      active organic ligands and therefore as modulators of radionuclide redox
      transformations and complexation in the subsurface.

PMID- 27694231
TI  - Genomic Comparisons of Lactobacillus crispatus and Lactobacillus iners Reveal
      Potential Ecological Drivers of Community Composition in the Vagina.
AB  - : Lactobacillus crispatus and Lactobacillus iners are common inhabitants of the
      healthy human vagina. These two species are closely related and are thought to
      perform similar ecological functions in the vaginal environment. Temporal data on
      the vaginal microbiome have shown that nontransient instances of cooccurrence are
      uncommon, while transitions from an L. iners-dominated community to one dominated
      by L. crispatus, and vice versa, occur often. This suggests that there is
      substantial overlap in the fundamental niches of these species. Given this
      apparent niche overlap, it is unclear how they have been maintained as common
      inhabitants of the human vagina. In this study, we characterized and compared the
      genomes of L. iners and L. crispatus to gain insight into possible mechanisms
      driving the maintenance of this species diversity. Our results highlight
      differences in the genomes of these two species that may facilitate the
      partitioning of their shared niche space. Many of the identified differences may
      impact the protective benefits provided to the host by these two species.
      IMPORTANCE: The microbial communities that inhabit the human vagina play a
      critical role in the maintenance of vaginal health through the production of
      lactic acid and lowering the environmental pH. This precludes the growth of
      nonindigenous organisms and protects against infectious disease. The two most
      common types of vaginal communities are dominated by either Lactobacillus iners
      or Lactobacillus crispatus, while some communities alternate between the two over
      time. We combined ecological theory with state-of-the-art genome analyses to
      characterize how these two species might partition their shared niche space in
      the vagina. We show that the genomes of L. iners and L. crispatus differ in many
      respects, several of which may drive differences in their competitive abilities
      in the vagina. Our results provide insight into factors that drive the
      complicated temporal dynamics of the vaginal microbiome and demonstrate how
      closely related microbial species partition shared fundamental niche space.

PMID- 27694233
TI  - Freshwater bacteria release methane as a byproduct of phosphorus acquisition.
AB  - : Freshwater lakes emit large amounts of methane, some of which is produced in
      oxic surface waters. Two potential pathways for aerobic methane production exist:
      methanogenesis in oxygenated water, which has been observed in some lakes, or
      demethylation of small organic molecules. Although methane is produced via
      demethylation in oxic marine environments, this mechanism of methane release has
      not yet been demonstrated in freshwater systems. Genes related to the C-P lyase
      pathway, which cleaves C-P bonds in phosphonate compounds, were found in a
      metagenomic survey of the surface water of Lake Matano, which is chronically P
      starved and methane-rich. We demonstrate that four bacterial isolates from Lake
      Matano obtain P from methylphosphonate and release methane, and that this
      activity is repressed by phosphate. We further demonstrate that expression of
      phnJ, which encodes the enzyme that releases methane, is higher in the presence
      of methylphosphonate and lower when both methylphosphonate and phosphate are
      added. This gene is also found in most of the metagenomic data sets from
      freshwater environments. These experiments link methylphosphonate degradation and
      methane production with gene expression and phosphate availability in freshwater
      organisms, and suggest that some of the excess methane in the Lake Matano surface
      water, and in other methane-rich lakes, may be produced by P-starved bacteria.
      IMPORTANCE: Methane is an important greenhouse gas, and contributes substantially
      to global warming. Although freshwater environments are known to release methane
      into the atmosphere, estimates of the amount of methane emitted by freshwater
      lakes vary from 8 to 73 Tg per year. Methane emissions are difficult to predict
      in part because the source of the methane can vary: it is the end product of the
      energy-conserving pathway in methanogenic archaea, which predominantly live in
      anoxic sediments or waters, but have also been identified in some oxic freshwater
      environments. More recently, methane release from small organic molecules has
      been observed in oxic marine environments. Here we show that demethylation of
      methylphosphonate may also contribute to methane release from lakes, and that
      phosphate can repress this activity. Since lakes are typically phosphorus
      limited, some methane release in these environments may be a byproduct of
      phosphorus metabolism, rather than carbon or energy metabolism. Methane emissions
      from lakes are currently predicted using primary production, eutrophication
      status, extent of anoxia, and the shape and size of the lake; to improve
      prediction of methane emissions, phosphorus availability and sources may also
      need to be included in these models.

PMID- 27694232
TI  - Listeria monocytogenes in Stone Fruits Linked to a Multistate Outbreak:
      Enumeration of Cells and Whole-Genome Sequencing.
AB  - : In 2014, the identification of stone fruits contaminated with Listeria
      monocytogenes led to the subsequent identification of a multistate outbreak.
      Simultaneous detection and enumeration of L. monocytogenes were performed on 105
      fruits, each weighing 127 to 145 g, collected from 7 contaminated lots. The
      results showed that 53.3% of the fruits yielded L. monocytogenes (lower limit of
      detection, 5 CFU/fruit), and the levels ranged from 5 to 2,850 CFU/fruit, with a
      geometric mean of 11.3 CFU/fruit (0.1 CFU/g of fruit). Two serotypes, IVb-v1 and
      1/2b, were identified by a combination of PCR- and antiserum-based serotyping
      among isolates from fruits and their packing environment; certain fruits
      contained a mixture of both serotypes. Single nucleotide polymorphism (SNP)-based
      whole-genome sequencing (WGS) analysis clustered isolates from two case-patients
      with the serotype IVb-v1 isolates and distinguished outbreak-associated isolates
      from pulsed-field gel electrophoresis (PFGE)-matched, but epidemiologically
      unrelated, clinical isolates. The outbreak-associated isolates differed by up to
      42 SNPs. All but one serotype 1/2b isolate formed another WGS cluster and
      differed by up to 17 SNPs. Fully closed genomes of isolates from the stone fruits
      were used as references to maximize the resolution and to increase our confidence
      in prophage analysis. Putative prophages were conserved among isolates of each
      WGS cluster. All serotype IVb-v1 isolates belonged to singleton sequence type 382
      (ST382); all but one serotype 1/2b isolate belonged to clonal complex 5.
      IMPORTANCE: WGS proved to be an excellent tool to assist in the epidemiologic
      investigation of listeriosis outbreaks. The comparison at the genome level
      contributed to our understanding of the genetic diversity and variations among
      isolates involved in an outbreak or isolates associated with food and
      environmental samples from one facility. Fully closed genomes increased our
      confidence in the identification and comparison of accessory genomes. The
      diversity among the outbreak-associated isolates and the inclusion of PFGE
      matched, but epidemiologically unrelated, isolates demonstrate the high
      resolution of WGS. The prevalence and enumeration data could contribute to our
      further understanding of the risk associated with Listeria monocytogenes
      contamination, especially among high-risk populations.

PMID- 27694234
TI  - Pendimethalin Nitroreductase Is Responsible for the Initial Pendimethalin
      Degradation Step in Bacillus subtilis Y3.
AB  - : Pendimethalin [N-(1-ethylpropyl)-2,6-dinitro-3,4-xylidine] is a selective
      preemergence dinitroaniline herbicide. Several fungi and bacteria have been
      reported to degrade pendimethalin, but the enzymes or genes involved in this
      process have not been characterized. Nitroreduction is the initial degradation
      and detoxification step for pendimethalin. In this study, a pendimethalin
      nitroreductase (PNR), responsible for the nitroreduction of pendimethalin, was
      purified from the pendimethalin-degrading strain Bacillus subtilis Y3. Based on a
      comparison of its mass fingerprints with all of the deduced proteins from the
      draft genome of strain Y3, a protein annotated as a nitroreductase was
      identified, and its corresponding encoding gene was termed pnr PNR was a
      functional homodimer with a subunit molecular mass of approximately 23 kDa. PNR
      reduced the C-6 nitro group of the aromatic ring of pendimethalin, yielding 2
      nitro-6-amino-N-(1-ethylpropyl)-3,4-xylidine. PNR could also catalyze the
      nitroreduction of three other major varieties of dinitroaniline herbicides,
      including butralin, oryzalin, and trifluralin. However, the number of reduced
      nitro groups was two instead of one, which differed from the nitroreduction of
      pendimethalin by PNR and which may be due to the symmetry in the chemical
      structures of the two nitro groups. A detoxification assay revealed that 2-nitro
      6-amino-N-(1-ethylpropyl)-3,4-xylidine (PNR-reduced pendimethalin) showed no
      inhibitory effect on the growth of Saccharomyces cerevisiae BY4741, whereas
      pendimethalin showed an obvious inhibitory effect on its growth, indicating the
      detoxification effect of pendimethalin by PNR. Therefore, PNR has potential in
      pendimethalin detoxification applications. This report describes an enzyme (and
      corresponding gene) involved in the biodegradation of pendimethalin and
      dinitroaniline herbicides. IMPORTANCE: Pendimethalin [N-(1-ethylpropyl)-2,6
      dinitro-3,4-xylidine] is a widely used selective preemergence dinitroaniline
      herbicide, and its residue has been frequently detected in the environment. The
      U.S. Environmental Protection Agency (EPA) has classified pendimethalin as a
      persistent bioaccumulative toxin. To date, no enzymes or genes involved in
      pendimethalin biodegradation have been reported. In the present study, the gene
      pnr, which encodes the nitroreductase PNR, responsible for the nitroreduction of
      pendimethalin, was cloned from the pendimethalin-degrading strain Bacillus
      subtilis Y3. PNR could also catalyze the nitroreduction of three other major
      varieties of dinitroaniline herbicides, including butralin, oryzalin, and
      trifluralin. The reduction of pendimethalin by PNR might eliminate its toxicity
      against Saccharomyces cerevisiae BY4741, indicating the application potential of
      PNR in the detoxification of pendimethalin.

PMID- 27694235
TI  - Internalization of Heterologous Sugar Transporters by Endogenous alpha-Arrestins
      in the Yeast Saccharomyces cerevisiae.
AB  - : When expressed in Saccharomyces cerevisiae using either of two constitutive
      yeast promoters (PGK1prom and CCW12prom), the transporters CDT-1 and CDT-2 from
      the filamentous fungus Neurospora crassa are able to catalyze, respectively,
      active transport and facilitated diffusion of cellobiose (and, for CDT-2, also
      xylan and its derivatives). In S. cerevisiae, endogenous permeases are removed
      from the plasma membrane by clathrin-mediated endocytosis and are marked for
      internalization through ubiquitinylation catalyzed by Rsp5, a HECT class
      ubiquitin:protein ligase (E3). Recruitment of Rsp5 to specific targets is
      mediated by a 14-member family of endocytic adaptor proteins, termed alpha
      arrestins. Here we demonstrate that CDT-1 and CDT-2 are subject to alpha-arrestin
      mediated endocytosis, that four alpha-arrestins (Rod1, Rog3, Aly1, and Aly2) are
      primarily responsible for this internalization, that the presence of the
      transport substrate promotes transporter endocytosis, and that, at least for CDT
      2, residues located in its C-terminal cytosolic domain are necessary for its
      efficient endocytosis. Both alpha-arrestin-deficient cells expressing CDT-2 and
      otherwise wild-type cells expressing CDT-2 mutants unresponsive to alpha-arrestin
      driven internalization exhibit an increased level of plasma membrane-localized
      transporter compared to that of wild-type cells, and they grow, utilize the
      transport substrate, and generate ethanol anaerobically better than control
      cells. IMPORTANCE: Ethanolic fermentation of the breakdown products of plant
      biomass by budding yeast Saccharomyces cerevisiae remains an attractive biofuel
      source. To achieve this end, genes for heterologous sugar transporters and the
      requisite enzyme(s) for subsequent metabolism have been successfully expressed in
      this yeast. For one of the heterologous transporters examined in this study, we
      found that the amount of this protein residing in the plasma membrane was the
      rate-limiting factor for utilization of the cognate carbon source (cellobiose)
      and its conversion to ethanol.

PMID- 27694236
TI  - Soil Nutrient Depletion Is Associated with the Presence of Burkholderia
      pseudomallei.
AB  - : Burkholderia pseudomallei is a soil-dwelling bacterium and the cause of
      melioidosis, which kills an estimated 89,000 people per year worldwide.
      Agricultural workers are at high risk of infection due to repeated exposure to
      the bacterium. Little is known about the soil physicochemical properties
      associated with the presence or absence of the organism. Here, we evaluated the
      soil physicochemical properties and presence of B. pseudomallei in 6,100 soil
      samples collected from 61 rice fields in Thailand. The presence of B.
      pseudomallei was negatively associated with the proportion of clay, proportion of
      moisture, level of salinity, percentage of organic matter, presence of cadmium,
      and nutrient levels (phosphorus, potassium, calcium, magnesium, and iron). The
      presence of B. pseudomallei was not associated with the level of soil acidity (P
      = 0.54). In a multivariable logistic regression model, the presence of B.
      pseudomallei was negatively associated with the percentage of organic matter
      (odds ratio [OR], 0.06; 95% confidence interval [CI], 0.01 to 0.47; P = 0.007),
      level of salinity (OR, 0.06; 95% CI, 0.01 to 0.74; P = 0.03), and percentage of
      soil moisture (OR, 0.81; 95% CI, 0.66 to 1.00; P = 0.05). Our study suggests that
      B. pseudomallei thrives in rice fields that are nutrient depleted. Some
      agricultural practices result in a decline in soil nutrients, which may impact
      the presence and amount of B. pseudomallei bacteria in affected areas.
      IMPORTANCE: Burkholderia pseudomallei is an environmental Gram-negative bacillus
      and the cause of melioidosis. Humans acquire the disease following skin
      inoculation, inhalation, or ingestion of the bacterium in the environment. The
      presence of B. pseudomallei in soil defines geographic regions where humans and
      livestock are at risk of melioidosis, yet little is known about the soil
      properties associated with the presence of the organism. We evaluated the soil
      properties and presence of B. pseudomallei in 61 rice fields in East, Central,
      and Northeast Thailand. We demonstrated that the organism was more commonly found
      in soils with lower levels of organic matter and nutrients, including phosphorus,
      potassium, calcium, magnesium, and iron. We also demonstrated that crop residue
      burning after harvest, which can reduce soil nutrients, was not uncommon. Some
      agricultural practices result in a decline in soil nutrients, which may impact
      the presence and amount of B. pseudomallei bacteria in affected areas.

PMID- 27694237
TI  - Ferredoxin:NAD+ Oxidoreductase of Thermoanaerobacterium saccharolyticum and Its
      Role in Ethanol Formation.
AB  - : Ferredoxin:NAD+ oxidoreductase (NADH-FNOR) catalyzes the transfer of electrons
      from reduced ferredoxin to NAD+ This enzyme has been hypothesized to be the main
      enzyme responsible for ferredoxin oxidization in the NADH-based ethanol pathway
      in Thermoanaerobacterium saccharolyticum; however, the corresponding gene has not
      yet been identified. Here, we identified the Tsac_1705 protein as a candidate
      FNOR based on the homology of its functional domains. We then confirmed its
      activity in vitro with a ferredoxin-based FNOR assay. To determine its role in
      metabolism, the tsac_1705 gene was deleted in different strains of T.
      saccharolyticum In wild-type T. saccharolyticum, deletion of tsac_1705 resulted
      in a 75% loss of NADH-FNOR activity, which indicated that Tsac_1705 is the main
      NADH-FNOR in T. saccharolyticum When both NADH- and NADPH-linked FNOR genes were
      deleted, the ethanol titer decreased and the ratio of ethanol to acetate
      approached unity, indicative of the absence of FNOR activity. Finally, we tested
      the effect of heterologous expression of Tsac_1705 in Clostridium thermocellum
      and found improvements in both the titer and the yield of ethanol. IMPORTANCE:
      Redox balance plays a crucial role in many metabolic engineering strategies.
      Ferredoxins are widely used as electron carriers for anaerobic microorganism and
      plants. This study identified the gene responsible for electron transfer from
      ferredoxin to NAD+, a key reaction in the ethanol production pathway of this
      organism and many other metabolic pathways. Identification of this gene is an
      important step in transferring the ethanol production ability of this organism to
      other organisms.

PMID- 27694238
TI  - Phylogenetic Evidence for Ancient and Persistent Environmental Symbiont
      Reacquisition in Largidae (Hemiptera: Heteroptera).
AB  - : The insect order Hemiptera, one of the best-studied insect lineages with
      respect to bacterial symbioses, still contains major branches that lack
      comprehensive characterization of associated bacterial symbionts. The
      Pyrrhocoroidea (Largidae [220 species] and Pyrrhocoridae [~300 species]) is a
      clade of the hemipteran infraorder Pentatomomorpha. Studies on bacterial
      symbionts of this group have focused on members of Pyrrhocoridae, but recent
      examination of species of two genera of Largidae demonstrated divergent symbiotic
      complexes in these putative sister families. We surveyed the associated bacterial
      diversity of this group using paired-end Illumina sequencing and targeted Sanger
      sequencing of bacterial 16S rRNA amplicons of 30 pyrrhocoroid taxa, including 17
      species of Largidae, in order to determine bacterial associates and the
      similarity of associated microbial communities among species. We also used
      molecular data (4,800 bp in 5 loci, for 57 ingroup and 12 outgroup taxa) to infer
      a phylogeny of the host superfamily, in order to trace the evolution of symbiotic
      complexes among Pentatomomorpha species. We undertook multiple lines of
      investigation (i.e., experimental rearing, fluorescence in situ hybridization
      microscopy, and phylogenetic and coevolutionary analyses) to elucidate potential
      transmission routes for largid symbionts. We found a prevalent and specific
      association of Largidae with Burkholderia strains of the plant-associated
      beneficial and environmental clade, housed in midgut tubules. As in other
      distantly related Heteroptera, symbiotic bacteria seem to be acquired from the
      environment every generation. We review the current understanding of symbiotic
      complexes within Pentatomomorpha and discuss means to further investigate the
      evolution and function of these symbioses. IMPORTANCE: Obligate symbioses with
      bacteria are common in insects, particularly Hemiptera, in which various forms of
      symbiosis occur. However, knowledge regarding symbionts remains incomplete for
      major hemipteran lineages. Thus, an accurate understanding of how these
      partnerships evolved and changed over millions of years is not yet achievable. We
      contribute to our understanding of the evolution of symbiotic complexes in
      Hemiptera by characterizing bacterial associates of Pyrrhocoroidea, focusing on
      the family Largidae. Members of Largidae are associated with specific symbiotic
      Burkholderia strains from a different clade than Burkholderia symbionts in other
      Burkholderia-associated Hemiptera. Evidence suggests that species of Largidae
      reacquire specific symbiotic bacteria from the environment every generation,
      which is a rare strategy for insects, with potentially volatile evolutionary
      ramifications, but one that must have persisted in Largidae and related lineages
      since their origin in the Cretaceous Period.

PMID- 27694239
TI  - Microbial Glucuronoyl Esterases: 10 Years after Discovery.
AB  - A carbohydrate esterase called glucuronoyl esterase (GE) was discovered 10 years
      ago in a cellulolytic system of the wood-rotting fungus Schizophyllum commune
      Genes coding for GEs were subsequently found in a number of microbial genomes,
      and a new family of carbohydrate esterases (CE15) has been established. The
      multidomain structures of GEs, together with their catalytic properties on
      artificial substrates and positive effect on enzymatic saccharification of plant
      biomass, led to the view that the esterases evolved for hydrolysis of the ester
      linkages between 4-O-methyl-d-glucuronic acid of plant glucuronoxylans and lignin
      alcohols, one of the crosslinks in the plant cell walls. This idea of the
      function of GEs is further supported by the effects of cloning of fungal GEs in
      plants and by very recently reported evidence for changes in the size of isolated
      lignin-carbohydrate complexes due to uronic acid de-esterification. These facts
      make GEs interesting candidates for biotechnological applications in plant
      biomass processing and genetic modification of plants. This article is a brief
      summary of current knowledge of these relatively recent and unexplored esterases.

PMID- 27694240
TI  - Novel Capsular Polysaccharide Loci and New Diagnostic Tools for High-Throughput
      Capsular Gene Typing in Streptococcus suis.
AB  - : Streptococcus suis is an important pathogen of pigs and may cause serious
      disease in humans. Serotyping is an important tool for detection and
      epidemiological studies of S. suis Thirty-three reference serotypes and nine
      novel cps loci (NCLs) are recognized in S. suis To gain a better understanding of
      the prevalence and genetic characteristics of NCLs, we investigated the serotype
      identity of 486 isolates isolated between 2013 and 2015 in China by capsular gene
      typing methods. Two hundred seventy-six isolates carried NCLs belonging to 16
      groups, 8 of which appear to have not been reported previously. These isolates
      showed autoagglutination, polyagglutination, or nonagglutination with reference
      antisera and thus were nonserotypeable. Almost all isolates carrying the unknown
      NCLs were encapsulated, with various capsular thicknesses, indicating that they
      are most likely novel serotypes. To simultaneously identify the currently
      recognized 17 NCLs, an 18-plex detection system using the Luminex xTAG universal
      array technology was developed. Our data also provide valuable genetic
      information for monitoring the variations within NCLs by investigating the
      genetic characteristics of different subtypes within NCLs. IMPORTANCE:
      Nonserotypeable Streptococcus suis isolates have been reported in many studies,
      and 9 novel cps loci (NCLs) have already been identified in nonserotypeable
      isolates. Moreover, novel cps loci are continually being found. The main purpose
      of this study was to investigate the prevalence and characteristics of NCLs in S.
      suis isolates recovered between 2013 and 2015 in China. This study provides
      valuable genetic information for monitoring the variations within NCLs.
      Meanwhile, a fast and cost-effective 18-plex detection system that can
      simultaneously identify the currently recognized 17 NCLs was developed in this
      study. This system will serve as a valuable tool for detecting known and
      identifying additional novel cps loci among nonserotypeable S. suis isolates.

PMID- 27694242
TI  - From Anticipatory Corpse to Posthuman God.
AB  - The essays in this issue of JMP are devoted to critical engagement of my book,
      The Anticipatory Corpse The essays, for the most part, accept the main thrust of
      my critique of medicine. The main thrust of the criticism is whether the scope of
      the critique is too totalizing, and whether the proposed remedy is sufficient. I
      greatly appreciate these interventions because they allow me this occasion to
      respond and clarify, and to even further extend the argument of my book. In this
      response essay, I maintain that the regnant social imaginary of medicine is the
      regnant social imaginary of our time. It is grounded in a specific ontotheology:
      where ontology is a power ontology; where material is malleable to the open-ended
      organization of power and dependent only on working out the efficient mechanisms
      of its enactment; where ethically it is oriented only to the immanent telos of
      utility maximization in the short run, and ultimately to some posthuman future in
      the long run. This ontotheology originates in the anticipatory corpse and is
      ordered toward some god-like posthuman being. The entire ontotheology finds
      enactment through the political economy of neoliberalism. This social imaginary
      constantly works to insulate itself from other social imaginaries through the use
      of its institutional power, through marginalization, circumscription, or
      absorption. The modern social imaginary of neoliberal societies marginalizes and
      politically isolates other social imaginaries, or transforms them into something
      acceptable to the neoliberal imaginary. Yet, these other social imaginaries could
      influence the larger social imaginary in novel ways, sometimes through withdrawal
      and sometimes through challenges. These other practices-again, usually practices
      ordered according to different ontological and teleological purposes-might serve
      as a source of renewal and transformation, but only if the practitioners of these
      other social imaginaries understand the ontotheological powers that they are up
      against.

PMID- 27694241
TI  - Interkingdom Cross-Feeding of Ammonium from Marine Methylamine-Degrading Bacteria
      to the Diatom Phaeodactylum tricornutum.
AB  - : Methylamines occur ubiquitously in the oceans and can serve as carbon,
      nitrogen, and energy sources for heterotrophic bacteria from different
      phylogenetic groups within the marine bacterioplankton. Diatoms, which constitute
      a large part of the marine phytoplankton, are believed to be incapable of using
      methylamines as a nitrogen source. As diatoms are typically associated with
      heterotrophic bacteria, the hypothesis came up that methylotrophic bacteria may
      provide ammonium to diatoms by degradation of methylamines. This hypothesis was
      investigated with the diatom Phaeodactylum tricornutum and monomethylamine (MMA)
      as the substrate. Bacteria supporting photoautotrophic growth of P. tricornutum
      with MMA as the sole nitrogen source could readily be isolated from seawater. Two
      strains, Donghicola sp. strain KarMa, which harbored genes for both
      monomethylamine dehydrogenase and the N methylglutamate pathway, and Methylophaga
      sp. strain M1, which catalyzed MMA oxidation by MMA dehydrogenase, were selected
      for further characterization. While strain M1 grew with MMA as the sole
      substrate, strain KarMa could utilize MMA as a nitrogen source only when, e.g.,
      glucose was provided as a carbon source. With both strains, release of ammonium
      was detected during MMA utilization. In coculture with P. tricornutum, strain
      KarMa supported photoautotrophic growth with 2 mM MMA to the same extent as with
      the equimolar amount of NH4Cl. In coculture with strain M1, photoautotrophic
      growth of P. tricornutum was also supported, but to a much lower degree than by
      strain KarMa. This proof-of-principle study with a synthetic microbial community
      suggests that interkingdom cross-feeding of ammonium from methylamine-degrading
      bacteria is a contribution to phytoplankton growth which has been overlooked so
      far. IMPORTANCE: Interactions between diatoms and heterotrophic bacteria are
      important for marine carbon cycling. In this study, a novel interaction is
      described. Bacteria able to degrade monomethylamine, which is a ubiquitous
      organic nitrogen compound in marine environments, can provide ammonium to
      diatoms. This interkingdom metabolite transfer enables growth under
      photoautotrophic conditions in coculture, which would not be possible in the
      respective monocultures. This proof-of-principle study calls attention to a so
      far overlooked contribution to phytoplankton growth.

PMID- 27694243
TI  - MicroRNAs and post-operative atrial fibrillation: a step in the understanding of
      the mechanism and identifying reliable biomarkers.

PMID- 27694245
TI  - More complex than expected?

PMID- 27694246
TI  - Reply to Fukunaga and Koyama.

PMID- 27694247
TI  - Reply to Choi and Stamm.

PMID- 27694248
TI  - Intercostal artery aneurysms: a rare presentation in Loey's-Dietz syndrome.

PMID- 27694250
TI  - Concerns about tricuspid leaflet augmentation for severe tricuspid regurgitation.

PMID- 27694251
TI  - Zonal organ allocation system and its impact on long-term outcomes after lung
      transplantation: a propensity score matched analysis?.
AB  - OBJECTIVE: Zonal organ allocation system comprises organ procurement by teams
      within a specific geographical area of each retrieval team. Therefore, in a
      substantial number of cases organs are retrieved by 'foreign' teams and are sent
      for transplantation to the implanting centre. The aim of this study was to assess
      the impact of zonal organ allocation system on early- and long-term outcomes
      after lung transplantation (LTx). METHODS: Included were 331 consecutive patients
      who underwent LTx performed at Harefield Hospital between January 2007 and
      January 2015. Recipients were divided into two groups depending on the organ
      retrieval team: 204 (61.6%) patients were transplanted using lungs procured by
      our institutional team (institutional group), whereas 127 (38.4%) organs were
      retrieved by other teams (external group) from experienced transplant centres in
      the UK. To exclude selection bias and other confounders, a 1:1 propensity score
      based matching procedure was performed resulting in a total number of 238 donors
      and recipients who were well matched for baseline characteristics. The primary
      end-points were overall survival after LTx and freedom from bronchiolitis
      obliterans syndrome (BOS). Secondary end-points were perioperative clinical
      characteristics as well as adverse events that occurred over the follow-up.
      RESULT: After propensity score matching all donor characteristics and all
      baseline recipient characteristics were statistically similar between the two
      groups. In terms of early postoperative results, both groups were statistically
      comparable. However, there was a trend towards higher incidence of primary graft
      dysfunction in the external group (P = 0.054). Regarding long-term results with
      up to 7 years of follow-up, the overall survival also appeared to be poorer in
      the external group; however, this difference did not reach statistical
      significance. The freedom from BOS over the long-term follow was significantly
      poorer in the external group (P = 0.040). CONCLUSION: Despite excellent early
      outcomes the zonal allocation system might be associated with significantly
      poorer long-term outcomes in terms of freedom from BOS after bilateral LTx.
      Further research is needed to find the underlying factors leading to these
      results.

PMID- 27694252
TI  - Fifteen years of surgery for acute type A aortic dissection in moderate-to-mild
      systemic hypothermia?.
AB  - OBJECTIVE: Surgery for acute type A aortic dissection remains a surgical
      challenge because of prolonged operative times, bleeding complications, and a
      considerable risk of neurological morbidity and mortality. The following study
      investigates the clinical results after surgical treatment for acute type A
      aortic dissection using selective antegrade cerebral perfusion and moderate-to
      mild systemic hypothermia (>=28  degrees C). METHODS: Between January 2000 and
      January 2015, 453 consecutive patients underwent surgical treatment for acute
      type A aortic dissection at two aortic referral centres in Germany. Patient mean
      age was 67 +/- 13 years, 298 patients (66%) were male. Selective unilateral or
      bilateral cerebral perfusion under moderate-to-mild systemic hypothermia was used
      in all patients. Ascending aortic replacement, hemiarch replacement and total
      arch replacement was performed in 9 patients (2%), 342 patients (75%) and 102
      patients (23%), respectively. Clinical data were prospectively entered into the
      institutional databases. Mean late follow-up was 6 +/- 3 years and was 98%
      complete. RESULTS: Cardiopulmonary bypass time totalled 181 +/- 68 min and the
      myocardial ischaemic time 107 +/- 43 min. Mean duration of selective antegrade
      cerebral was 46 +/- 23 min. Mean lowest core temperature amounted to 28.8 +/- 0.6
      degrees C. Unilateral cerebral perfusion was performed in 298 patients (66%) and
      bilateral in 155 patients (34%). Mean intensive care unit stay was 5 +/- 7 days.
      We observed new postoperative permanent neurological deficits in 27 patients (6%)
      and transient neurological deficits in 31 patients (7%). Thirty-day mortality was
      7% (n = 32). Overall survival rate at 5 years was 77 +/- 6%. CONCLUSIONS: Our
      data suggest that selective antegrade cerebral perfusion in combination with
      moderate-to-mild systemic hypothermia (>=28  degrees C) can be safely and
      reproducibly applied to surgery for acute type A aortic dissection and offers
      sufficient neurological and visceral organ protection.

PMID- 27694254
TI  - Microscopy in this issue.

PMID- 27694253
TI  - Neoadjuvant chemoradiotherapy or chemotherapy? A comprehensive systematic review
      and meta-analysis of the options for neoadjuvant therapy for treating oesophageal
      cancer.
AB  - Neoadjuvant therapy followed by surgery is a standard treatment for locally
      advanced oesophageal cancer. However, the roles of neoadjuvant chemoradiotherapy
      and chemotherapy in treating oesophageal cancer remain controversial. In this
      comprehensive meta-analysis, we examine the efficacy of adding radiotherapy to
      neoadjuvant chemotherapy for treating oesophageal cancer as reported in qualified
      randomized controlled trials (RCTs). We conducted a systematic literature search
      using PubMed, Embase, Cochrane Library databases, Google Scholar and the American
      Society of Clinical Oncology database to identify relevant studies up to 31 March
      2016. Data including the pathological complete response rate, R0 resection rate
      and 3-year survival rate were extracted and analysed. Five qualified RCTs were
      included with a total of 709 patients. Meta-analysis showed that neoadjuvant
      chemoradiotherapy significantly increases the rates of pathological complete
      response and R0 resection in patients with oesophageal adenocarcinoma or squamous
      cell carcinoma (SCC). However, we found a significantly increased 3-year survival
      rate only in oesophageal SCC patients treated with neoadjuvant chemoradiotherapy
      compared with neoadjuvant chemotherapy (56.8 and 42.8%, respectively); relative
      risk (RR): 1.31 [95% confidence interval (CI) 1.10-1.58, P = 0.003]. In
      oesophageal adenocarcinoma patients, no significant survival benefit of
      neoadjuvant chemoradiotherapy was found compared with neoadjuvant chemotherapy
      alone (46.3 and 41.0%, respectively; RR: 1.13, 95% CI 0.88-1.45, P = 0.34). Our
      meta-analysis adds to the evidence showing that neoadjuvant chemoradiotherapy
      should be the standard preoperative treatment strategy for locally advanced
      oesophageal SCC. For oesophageal adenocarcinoma, neoadjuvant chemotherapy alone
      may be the best preoperative treatment strategy to avoid the risk of adverse
      effects of radiotherapy.

PMID- 27694255
TI  - European drug agency to appeal ruling that it stop releasing trial data.

PMID- 27694256
TI  - Vestibular neuritis affects both superior and inferior vestibular nerves.
AB  - OBJECTIVE: To characterize the profiles of afferent dysfunction in a cross
      section of patients with acute vestibular neuritis using tests of otolith and
      semicircular canal function sensitive to each of the 5 vestibular end organs.
      METHODS: Forty-three patients fulfilling clinical criteria for acute vestibular
      neuritis were recruited between 2010 and 2016 and studied within 10 days of
      symptom onset. Otolith function was evaluated with air-conducted cervical and
      bone-conducted ocular/vestibular evoked myogenic potentials and the subjective
      visual horizontal test. Canal-plane video head impulse tests (vHITs) assessed the
      function of each semicircular canal. Patterns of recovery were investigated in 16
      patients retested after a 6- to 12-month follow-up period. RESULTS: Rates of
      horizontal canal (97.7%), anterior canal (90.7%), and utricular (72.1%)
      dysfunction were significantly higher than rates of posterior canal (39.5%) and
      saccular (39.0%) dysfunction (p < 0.008). Twenty-four patients (55.8%) had
      abnormalities localizing to both vestibular nerve divisions; 18 patients (41.9%)
      had superior neuritis; and 1 patient (2.3%) had inferior neuritis. A test battery
      that included horizontal and posterior canal vHIT and the cervical/vestibular
      evoked myogenic potentials identified superior or inferior neuritis in all
      patients tested acutely. Eight of 16 patients who were retested at follow-up had
      recovered a normal vestibular evoked myogenic potential and vHIT profile.
      CONCLUSIONS: Acute vestibular neuritis most often affects both vestibular nerve
      divisions. The horizontal vHIT alone identifies superior nerve dysfunction in all
      patients with vestibular neuritis tested acutely, whereas both
      cervical/vestibular evoked myogenic potentials and posterior vHIT are necessary
      for diagnosing inferior vestibular nerve involvement.

PMID- 27694258
TI  - Introducing the Axon Registry: An opportunity to improve quality of neurologic
      care.
AB  - Clinical quality data registries are increasingly popular tools used by providers
      to improve the quality of clinical care and satisfy growing numbers of regulatory
      and reporting requirements. Specialty societies use registries to provide value
      to their members and guide improvements in care at the population level. In this
      article, we outline the rationale, structure, function, and challenges related to
      the American Academy of Neurology's development of its own clinical quality data
      registry: the Axon Registry.

PMID- 27694257
TI  - Plasma tau in Alzheimer disease.
AB  - OBJECTIVE: To test whether plasma tau is altered in Alzheimer disease (AD) and
      whether it is related to changes in cognition, CSF biomarkers of AD pathology
      (including beta-amyloid [Abeta] and tau), brain atrophy, and brain metabolism.
      METHODS: This was a study of plasma tau in prospectively followed patients with
      AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive
      healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative
      (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive
      impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n
      = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and
      Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284
      participants were studied. Associations were tested between plasma tau and
      diagnosis, CSF biomarkers, MRI measures, 18fluorodeoxyglucose-PET, and cognition.
      RESULTS: Higher plasma tau was associated with AD dementia, higher CSF tau, and
      lower CSF Abeta42, but the correlations were weak and differed between ADNI and
      BioFINDER. Longitudinal analysis in ADNI showed significant associations between
      plasma tau and worse cognition, more atrophy, and more hypometabolism during
      follow-up. CONCLUSIONS: Plasma tau partly reflects AD pathology, but the overlap
      between normal aging and AD is large, especially in patients without dementia.
      Despite group-level differences, these results do not support plasma tau as an AD
      biomarker in individual people. Future studies may test longitudinal plasma tau
      measurements in AD.

PMID- 27694259
TI  - Rebleeding in cerebral amyloid angiopathy: Inside out or outside in?

PMID- 27694261
TI  - The AAN's Axon Registry: Mastering how we are measured.

PMID- 27694260
TI  - Whole-exome sequencing identifies a missense mutation in hnRNPA1 in a family with
      flail arm ALS.
AB  - OBJECTIVE: To identify the disease-causing gene of a family with upper limb
      predominant, slowly progressive amyotrophic lateral sclerosis (ALS), which was
      diagnosed as flail arm syndrome (FAS). METHODS: After causation of 24 known ALS
      genes was excluded by targeted next-generation sequencing, whole-exome sequencing
      was applied in the FAS family. Cellular localization of mutant hnRNPA1 was
      examined in transfected HeLa cells. An additional 251 Chinese patients with ALS
      (including 7 sporadic FAS) underwent mutation screening of hnRNPA1. RESULTS: We
      detected a novel missense mutation in hnRNPA1, c.862/1018C>T (p.P288S/P340S),
      which cosegregated with disease in the FAS family. The residue is highly
      conserved across species and exists in the encoded PY nuclear localization signal
      of hnRNPA1 protein. Mutant hnRNPA1 showed altered intracellular localization,
      resulting in formation of cytoplasmic inclusions that colocalized with stress
      granules in transfected cells. Further mutation screening of hnRNPA1 in
      additional patients with FAS and typical ALS detected 2 rare variants with
      unknown significance. These variants lie in the prion-like domain of hnRNPA1 long
      isoform, which was detected exclusively in the CNS. CONCLUSIONS: Our results
      suggest that hnRNPA1 is the causative gene in the family with flail arm ALS. This
      further expanded the disease phenotype of hnRNPA1 mutations.

PMID- 27694262
TI  - Quality of life at 6 months in the Idiopathic Intracranial Hypertension Treatment
      Trial.
AB  - OBJECTIVE: To examine the changes in vision-specific and overall health-related
      quality of life (QOL) at 6 months in participants with idiopathic intracranial
      hypertension (IIH) and mild visual loss enrolled in the Idiopathic Intracranial
      Hypertension Treatment Trial (IIHTT) and to determine the signs and symptoms of
      IIH that mediate the effect of acetazolamide on QOL. METHODS: We assessed QOL
      using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25),
      the 10-Item NEI-VFQ-25 Neuro-Ophthalmic Supplement, and the 36-Item Short Form
      Health Survey (SF-36). We examined associations among changes in QOL measures
      over 6 months, treatment status, and changes in signs and symptoms using linear
      and structural equation models. RESULTS: Among the 165 participants with IIH (86
      randomized to acetazolamide, 79 to placebo), beneficial effects of acetazolamide
      were seen on all QOL scales evaluated, as well as on the Near Activities (5.60
      points, p = 0.03), Social Functioning (3.85 points, p = 0.04), and Mental Health
      (9.82, p = 0.04) subscales of the NEI-VFQ-25. Positive acetazolamide-related
      effects on QOL appeared to be primarily mediated by improvements in visual field,
      neck pain, pulsatile tinnitus, and dizziness/vertigo that outweighed the side
      effects of acetazolamide. CONCLUSIONS: The marked reductions in baseline QOL seen
      among patients with mild visual loss from IIH are improved by treatment with
      acetazolamide. When combined with acetazolamide-associated improvements in visual
      field and other aspects of IIH, our findings with respect to QOL provide further
      support from the IIHTT in favor of acetazolamide to augment a dietary
      intervention in the treatment of IIH with mild visual loss (clinicaltrials.gov:
      NCT01003639).

PMID- 27694263
TI  - How long should we wait to start oral anticoagulation after cardioembolic stroke?

PMID- 27694264
TI  - Cluster headache and depression.
AB  - OBJECTIVE: As cluster headache (CH) is often referred to as "suicide headache,"
      we wanted to assess the prevalence of depression in CH patients, and to
      investigate determinants of depression such as sleep disturbances. METHODS: In a
      cross-sectional, web-based, validated questionnaire study among 462 well-defined
      CH patients and 177 controls, we diagnosed CH according to the ICHD-III. We
      assessed depression using the Hospital Anxiety and Depression Scale (HADS-D) and
      the Center for Epidemiologic Studies Depression scale (CES-D) with supplementary
      questions to assess lifetime depression. Data were analyzed with logistic and
      linear regression models. RESULTS: Lifetime depression showed almost 3 times
      higher odds in CH patients (n = 462) than controls (n = 177) (odds ratio 2.77;
      95% confidence interval 1.70-4.51). Chronic (n = 67) vs episodic (n = 394)
      patients had a higher prevalence of lifetime depression and more sleeping
      problems. Current depression was associated with having active attacks (last
      attack <1 month) (adjusted p = 0.02), but no effect remained after correction for
      sleep disturbances. CONCLUSIONS: CH is associated with an almost 3 times
      increased odds of lifetime depression. Current depression is highly prevalent in
      patients with active disease, in part related to sleep disturbances due to
      current nocturnal attacks.

PMID- 27694265
TI  - Prediction of 3-year clinical course in CADASIL.
AB  - OBJECTIVE: To obtain simple models predicting disease evolution at 3 years for a
      given patient with cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL). METHODS: Based on data obtained in a
      prospective study of 236 patients, we built and validated models predicting, at
      the individual level, 3-year changes in Mini-Mental State Examination (MMSE),
      Mattis Dementia Rating Scale (MDRS), Trail Making Test version B (TMTB), and
      modified Rankin Scale (mRS). These models were based on different sets of
      predictors obtained at baseline, including either clinical data (epidemiologic
      data and cardiovascular risk factors) or clinical data and quantitative MRI
      markers (volume of lacunes [LLV], volume of white matter hyperintensities,
      normalized brain volume [BPF], number of microbleeds). The Bayesian information
      criterion (BIC) and the coefficient of determination (R2) were used to determine
      models with the highest predictive ability and the lowest numbers of predictors.
      RESULTS: We obtained validated models with a demonstrated ability to predict, for
      a given patient, 3-year changes in MMSE, MDRS, TMTB, and mRS (R2 on independent
      samples: 0.22, 0.12, 0.09, and 0.17, respectively). In all cases, the best models
      according to R2 and BIC values included only the baseline values of the outcome,
      of BPF, and of LLV. Inclusion of other potential predictors always led to a loss
      of generalizability. CONCLUSIONS: The prediction of 3-year changes in MMSE, MDRS,
      TMTB, and mRS for a given patient with CADASIL can be obtained using simple
      models relying only on the initial values of the considered score, BPF, and LLV.

PMID- 27694266
TI  - Early start of DOAC after ischemic stroke: Risk of intracranial hemorrhage and
      recurrent events.
AB  - OBJECTIVE: In patients with recent acute ischemic stroke (AIS) and atrial
      fibrillation, we assessed the starting time of direct, non-vitamin K antagonist
      oral anticoagulants (DOACs) for secondary prevention, the rate of intracranial
      hemorrhage (ICH), and recurrent ischemic events during follow-up. METHODS: We
      included consecutive patients with nonvalvular atrial fibrillation admitted to
      our hospital for AIS or TIA (index event) who received secondary prophylaxis with
      DOAC or vitamin K antagonists (VKAs). Follow-up was at least 3 months. In the
      primary analysis, we compared rates of ICH and recurrent ischemic events (AIS or
      TIA) between patients with early (<=7 days since event; DOACearly) and those with
      late (>7 days, DOAClate) start of DOAC. RESULTS: Two hundred four patients were
      included (median age 79 years, 89% AIS) and total follow-up time was 78.25
      patient-years. One hundred fifty-five patients received DOAC with a median delay
      of 5 days after the index event (interquartile range 3-11) and 49 received VKA.
      DOAC was started early in 100 patients (65%). We observed one ICH (1.3%/y) and 6
      recurrent AIS (7.7%/y). The ICH occurred in a patient taking VKA. No significant
      difference in the rate of recurrent AIS between DOACearly (5.1%/y) and DOAClate
      (9.3%/y, p = 0.53) was observed. CONCLUSIONS: Even if DOACs are often started
      early after an index event, the risk of ICH appears to be low. Among all patients
      receiving anticoagulation, the rate of recurrent events was 6 times higher than
      the rate of ICH.

PMID- 27694267
TI  - MRI-negative temporal lobe epilepsy: A network disorder of neocortical
      connectivity.
AB  - OBJECTIVE: To define the functional network changes that characterize MRI
      negative temporal lobe epilepsy (TLE) and TLE with hippocampal sclerosis (HS
      TLE). METHODS: We studied 36 patients with medically refractory unilateral TLE,
      having either a normal clinical MRI (n = 18) or unilateral hippocampal sclerosis
      (n = 18). Patients were compared to healthy controls of equivalent age and sex (n
      = 27). Functional connectivity in 10 minutes of task-free functional MRI was
      assessed using a voxel-resolution graph theoretic analysis, using the metrics of
      degree, clustering coefficient, eigenvector, and betweenness centrality.
      Significant clusters were further explored with a seed-based analysis. RESULTS:
      MRI-negative TLE showed decreased connectivity at the ipsilateral superior and
      middle temporal gyri compared to controls (decreased eigenvector centrality). No
      functional abnormality was detected within mesial temporal structures. In
      contrast, HS-TLE showed increased connectivity within the affected hippocampus
      and anterior thalamus (increased clustering coefficient) and decreased
      connectivity of the ventromesial prefrontal cortex (decreased betweenness
      centrality). Using the detected clusters as seed regions revealed decreased
      connectivity from the sclerotic hippocampus to both the contralateral temporal
      lobe and regions of the default mode network. CONCLUSION: MRI-negative TLE is
      associated with impaired interictal connectivity of the temporal neocortex,
      lateralized to the epileptic side. HS-TLE shows a different pattern, with
      functional segregation of the sclerotic hippocampus and impairment of its long
      range connectivity. This suggests that MRI-negative TLE is not merely a subtle
      version of hippocampal sclerosis, but is rather a separate condition that
      involves distinct brain networks.

PMID- 27694269
TI  - Distal Metatarsal Osteotomy for Moderate to Severe Hallux Valgus.
AB  - : Hallux valgus is the most common disorder of the hallux and often results in
      pain, functional disability, and impaired gait patterns. The goals of surgical
      management are to correct the deformity while improving patients' pain and
      function. Traditional treatment of moderate to severe hallux valgus deformities
      consist of proximal osteotomy and/or arthrodesis given their powerful corrective
      ability. Despite their corrective power, proximal osteotomies are more
      technically demanding, have a higher rate of complications, and require a more
      restricted post-operative recovery. We present an alternative technique for the
      treatment of moderate to severe hallux valgus. With this operation, a single
      distal medial incision is utilized to create a chevron osteotomy and lateral
      release. This procedure can achieve and maintain the desired correction and
      outcome without the need for a protracted recovery period. LEVEL OF EVIDENCE:
      Level V, expert opinion.

PMID- 27694268
TI  - Cortical superficial siderosis predicts early recurrent lobar hemorrhage.
AB  - OBJECTIVE: To identify predictors of early lobar intracerebral hemorrhage (ICH)
      recurrence, defined as a new ICH within 6 months of the index event, in patients
      with cerebral amyloid angiopathy (CAA). METHODS: Participants were consecutive
      survivors (age >=55 years) of spontaneous symptomatic probable or possible CAA
      related lobar ICH according to the Boston criteria, drawn from an ongoing single
      center cohort study. Neuroimaging markers ascertained in CT or MRI included focal
      (<=3 sulci) or disseminated (>3 sulci) cortical superficial siderosis (cSS),
      acute convexity subarachnoid hemorrhage (cSAH), cerebral microbleeds, white
      matter hyperintensities burden and location, and baseline ICH volume.
      Participants were followed prospectively for recurrent symptomatic ICH. Cox
      proportional hazards models were used to identify predictors of early recurrent
      ICH adjusting for potential confounders. RESULTS: A total of 292 patients were
      enrolled. Twenty-one patients (7%) had early recurrent ICH. Of these, 24% had
      disseminated cSS on MRI and 19% had cSAH on CT scan. In univariable analysis, the
      presence of disseminated cSS, cSAH, and history of previous ICH were predictors
      of early recurrent ICH (p < 0.05 for all comparisons). After adjusting for age
      and history of previous ICH, disseminated cSS on MRI and cSAH on CT were
      independent predictors of early recurrent ICH (hazard ratio [HR] 3.92, 95%
      confidence interval [CI] 1.38-11.17, p = 0.011, and HR 3.48, 95% CI 1.13-10.73, p
      = 0.030, respectively). CONCLUSIONS: Disseminated cSS on MRI and cSAH on CT are
      independent imaging markers of increased risk for early recurrent ICH. These
      markers may provide additional insights into the mechanisms of ICH recurrence in
      patients with CAA.

PMID- 27694270
TI  - Letter Regarding: Early Complications and Secondary Procedures in Transfibular
      Total Ankle Replacement.

PMID- 27694271
TI  - Response to "Letter Regarding: Early Complications and Secondary Procedures in
      Transfibular Total Ankle Replacement".

PMID- 27694272
TI  - Letter Regarding: Rotational Dynamics of the Normal Distal Tibiofibular Joint
      With Weight-Bearing Computed Tomography.

PMID- 27694273
TI  - Response to "Letter Regarding: Rotational Dynamics of the Normal Distal
      Tibiofibular Joint With Weight-Bearing Computed Tomography".

PMID- 27694275
TI  - Effect of cricoid pressure on laryngeal view during prehospital tracheal
      intubation: a propensity-based analysis.
AB  - BACKGROUND: The benefit of cricoid pressure during tracheal intubation is still
      debated and, due to its potential negative impact on laryngeal views, its routine
      use is questioned. The goal of this study was to estimate its impact on laryngeal
      view. METHODS: All patients intubated in the prehospital setting were included.
      Three different propensity score (PS) models were used and compared in terms of
      the balance achieved between those patients who received cricoid pressure and
      those who did not. The PS model that optimised the balance was retained in order
      to estimate the relationship between cricoid pressure and the following outcomes:
      difficult laryngoscopy, intubation-related complications and difficult
      intubation. RESULTS: Among the 1195 patients included, 499 (41.7%) received
      cricoid pressure. The optimal PS included seven variables (cardiac arrest,
      altered neurological status, shock, respiratory distress, gender, obesity,
      patient's position). After PS matching, no significant risk difference (RD) in
      the rate of difficult laryngoscopy was found between the patients who received
      cricoid pressure and those who did not (RD=0.001, 95% CI -0.07 to 0.08, p=0.50).
      No significant difference was found in terms of difficult intubation (RD=0.06,
      95% CI -0.13 to 0.25, p=0.28) and in terms of prevalence of complications, except
      for airway trauma that were more frequent in cricoid pressure group (RD=0.03, 95%
      CI 0.002 to 0.05, p=0.01). CONCLUSIONS: No significant relationship was found
      between the use of cricoid pressure for prehospital intubation and difficult
      laryngoscopy. Cricoid pressure was found to be associated with more airway
      trauma. This finding could question its routine use.

PMID- 27694276
TI  - Dynamic contrast-enhanced MRI measurement of renal function in healthy
      participants.
AB  - Background High repeatability, accuracy, and precision for renal function
      measurements need to be achieved to establish renal dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) as a clinically useful diagnostic tool.
      Purpose To investigate the repeatability, accuracy, and precision of DCE-MRI
      measured renal perfusion and glomerular filtration rate (GFR) using iohexol-GFR
      as the reference method. Material and Methods Twenty healthy non-smoking
      volunteers underwent repeated DCE-MRI and an iohexol-GFR within a period of 10
      days. Single-kidney (SK) MRI measurements of perfusion (blood flow, Fb) and
      filtration (GFR) were derived from parenchymal intensity time curves fitted to a
      two-compartment filtration model. The repeatability of the SK-MRI measurements
      was assessed using coefficient of variation (CV). Using iohexol-GFR as reference
      method, the accuracy of total MR-GFR was determined by mean difference (MD) and
      precision by limits of agreement (LoA). Results SK-Fb (MR1, 345 +/- 84; MR2, 371
      +/- 103 mL/100 mL/min) and SK-GFR (MR1, 52 +/- 14; MR2, 54 +/- 10 mL/min/1.73 m2)
      measurements achieved a repeatability (CV) in the range of 15-22%. With reference
      to iohexol-GFR, MR-GFR was determined with a low mean difference but high LoA
      (MR1, MD 1.5 mL/min/1.73 m2, LoA [-42, 45]; MR2, MD 6.1 mL/min/1.73 m2, LoA [-26,
      38]). Eighty percent and 90% of MR-GFR measurements were determined within +/-
      30% of the iohexol-GFR for MR1 and MR2, respectively. Conclusion Good
      repeatability of SK-MRI measurements and good agreement between MR-GFR and
      iohexol-GFR provide a high clinical potential of DCE-MRI for renal function
      assessment. A moderate precision in MR-derived estimates indicates that the
      method cannot yet be used in clinical routine.

PMID- 27694277
TI  - A Longitudinal Study of Maternal and Child Internalizing Symptoms Predicting
      Early Adolescent Emotional Eating.
AB  - Objective: To examine maternal and child internalizing symptoms as predictors of
      early adolescent emotional eating in a longitudinal framework spanning three
      critical developmental periods (preschool, elementary school, and early
      adolescence). Methods: Participants were 170 children recruited at preschool age
      for a longitudinal study. When children were 5.25 years, their mothers completed
      ratings of their own internalizing symptoms. During the spring of 4th grade,
      children completed measures of internalizing symptoms. In early adolescence,
      youth completed a measure of emotional eating. Results: Maternal and child
      internalizing symptoms predicted adolescent emotional eating. The results
      indicated that child psychopathology moderated the association between maternal
      psychopathology (except for maternal anxiety) and early adolescent emotional
      eating. There was no evidence of mediation. Conclusions: Pediatric psychologists
      are encouraged to provide early screening of, and interventions for, maternal and
      child internalizing symptoms to prevent children's emotional eating.

PMID- 27694278
TI  - Staging of Fatty Liver Diseases Based on Hierarchical Classification and Feature
      Fusion for Back-Scan-Converted Ultrasound Images.
AB  - Fatty liver disease is progressive and may not cause any symptoms at early
      stages. This disease is potentially fatal and can cause liver cancer in severe
      stages. Therefore, diagnosing and staging fatty liver disease in early stages is
      necessary. In this paper, a novel method is presented to classify normal and
      fatty liver, as well as discriminate three stages of fatty liver in ultrasound
      images. This study is performed with 129 subjects including 28 normal, 47
      steatosis, 42 fibrosis, and 12 cirrhosis images. The proposed approach uses back
      scan conversion of ultrasound sector images and is based on a hierarchical
      classification. The proposed algorithm is performed in two parts. The first part
      selects the optimum regions of interest from the focal zone of the back-scan
      converted ultrasound images. In the second part, discrimination between normal
      and fatty liver is performed and then steatosis, fibrosis, and cirrhosis are
      classified in a hierarchical basis. The wavelet packet transform and gray-level
      co-occurrence matrix are used to obtain a number of statistical features. A
      support vector machine classifier is used to discriminate between normal and
      fatty liver, and stage fatty cases. The results of the proposed scheme clearly
      illustrate the efficiency of this system with overall accuracy of 94.91% and also
      specificity of more than 90%.

PMID- 27694279
TI  - The use of mobile applications to support self-management for people with asthma:
      a systematic review of controlled studies to identify features associated with
      clinical effectiveness and adherence.
AB  - Objectives: Telehealth is promoted as a strategy to support self-management of
      long-term conditions. The aim of this systematic review is to identify which
      information and communication technology features implemented in mobile apps to
      support asthma self-management are associated with adoption, adherence to usage,
      and clinical effectiveness. Methods: We systematically searched 9 databases,
      scanned reference lists, and undertook manual searches (January 2000 to April
      2016). We include randomized controlled trials (RCTs) and quasiexperimental
      studies with adults. All eligible papers were assessed for quality, and we
      extracted data on the features included, health-related outcomes (asthma control,
      exacerbation rate), process/intermediate outcomes (adherence to monitoring or
      treatment, self-efficacy), and level of adoption of and adherence to use of
      technology. Meta-analysis and narrative synthesis were used. Results: We included
      12 RCTs employing a range of technologies. A meta-analysis (n = 3) showed
      improved asthma control (mean difference -0.25 [95% CI, -0.37 to -0.12]).
      Included studies incorporated 10 features grouped into 7 categories (education,
      monitoring/electronic diary, action plans, medication reminders/prompts,
      facilitating professional support, raising patient awareness of asthma control,
      and decision support for professionals). The most successful interventions
      included multiple features, but effects on health-related outcomes were
      inconsistent. No studies explicitly reported adoption of and adherence to the
      technology system. Conclusion: Meta-analysis of data from 3 trials showed
      improved asthma control, though overall the clinical effectiveness of apps,
      typically incorporating multiple features, varied. Further studies are needed to
      identify the features that are associated with adoption of and adherence to use
      of the mobile app and those that improve health outcomes.

PMID- 27694280
TI  - Patterns of Comorbidity Among Girls With ADHD: A Meta-analysis.
AB  - CONTEXT: Although children with attention-deficit/hyperactivity disorder (ADHD)
      are at elevated risk for comorbid psychopathology, the clinical correlates of
      ADHD in girls are far less understood relative to boys, despite ADHD being one of
      the most common childhood disorders in girls. OBJECTIVE: To meta-analytically
      summarize rates of comorbid internalizing (anxiety, depression) and externalizing
      (oppositional defiant disorder [ODD], conduct disorder [CD]) psychopathology
      among girls with and without ADHD. DATA SOURCES: Literature searches (PubMed,
      Google Scholar) identified published studies examining comorbid psychopathology
      in girls with and without ADHD. STUDY SELECTION: Eighteen studies (1997
      participants) met inclusion criteria and had sufficient data for the meta
      analysis. DATA EXTRACTION: Odds ratios for each comorbid disorder were calculated
      from available data. Demographic (eg, age, race/ethnicity) and study
      characteristics (eg, referral source, diagnostic method) were also coded.
      RESULTS: Compared with girls without ADHD, girls with ADHD were significantly
      more likely to meet Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition criteria for each comorbid disorder assessed. Relative odds were higher
      for externalizing (ODD: 5.6*; CD: 9.4*) relative to internalizing disorders
      (anxiety: 3.2*; depression: 4.2*). Meta-regression revealed larger effect sizes
      of ADHD on anxiety for studies using multiple diagnostic methods, featuring
      younger children, and including clinic-referred (versus community-referred)
      girls; the effect of ADHD on ODD varied based on diagnostic informant.
      LIMITATIONS: Findings were derived from cross-sectional studies, precluding
      causal inferences. CONCLUSIONS: Girls with ADHD frequently exhibit comorbid
      externalizing and internalizing disorders. We discuss future research priorities
      and consider intervention implications for ADHD and comorbid psychopathology in
      girls.

PMID- 27694281
TI  - Interventions to Improve Patient Safety During Intubation in the Neonatal
      Intensive Care Unit.
AB  - OBJECTIVE: To improve patient safety in our NICU by decreasing the incidence of
      intubation-associated adverse events (AEs). METHODS: We sequentially implemented
      and tested 3 interventions: standardized checklist for intubation, premedication
      algorithm, and computerized provider order entry set for intubation. We compared
      baseline data collected over 10 months (period 1) with data collected over a 10
      month intervention and sustainment period (period 2). Outcomes were the
      percentage of intubations containing any prospectively defined AE and intubations
      with bradycardia or hypoxemia. We followed process measures for each
      intervention. We used risk ratios (RRs) and statistical process control methods
      in a times series design to assess differences between the 2 periods. RESULTS:
      AEs occurred in 126/273 (46%) intubations during period 1 and 85/236 (36%)
      intubations during period 2 (RR = 0.78; 95% confidence interval [CI], 0.63-0.97).
      Significantly fewer intubations with bradycardia (24.2% vs 9.3%, RR = 0.39; 95%
      CI, 0.25-0.61) and hypoxemia (44.3% vs 33.1%, RR = 0.75, 95% CI 0.6-0.93)
      occurred during period 2. Using statistical process control methods, we
      identified 2 cases of special cause variation with a sustained decrease in AEs
      and bradycardia after implementation of our checklist. All process measures
      increased reflecting sustained improvement throughout data collection.
      CONCLUSIONS: Our interventions resulted in a 10% absolute reduction in AEs that
      was sustained. Implementation of a standardized checklist for intubation made the
      greatest impact, with reductions in both AEs and bradycardia.

PMID- 27694282
TI  - The effects of a 50-Hz magnetic field on the cardiovascular system in rats.
AB  - A 50-Hz magnetic field (MF) is a potential health-risk factor. Its effects on the
      cardiovascular system have not been fully investigated. This study was conducted
      to explore the effects of long-term exposure to a 50-Hz MF on the cardiovascular
      system. In the study, an exposure system was constructed, and the distribution of
      the 50-Hz MF was determined. Sixty-four Sprague-Dawley (SD) rats were exposed to
      a 50-Hz MF at 100 MUT for 24 weeks, 20 h per day, while another 64 rats were sham
      exposed. During the exposure, blood pressure was measured every 4 weeks. After 24
      weeks, echocardiography, cardiac catheterization and electrocardiography were
      performed. Moreover, heart and body weight were recorded, and haematoxylin-eosin
      staining and real-time PCR were conducted. The results showed that compared with
      the sham group, exposure to a 50-Hz MF did not exert any effects on blood
      pressure, pulse rate, heart rate or cardiac rhythm. Furthermore, echocardiography
      and cardiac catheterization showed that there were no significant differences in
      the cardiac morphology or haemodynamics. In addition, histopathological
      examination showed that exposure to a 50-Hz MF had no effects on the structure of
      the heart. Finally, expression of the cardiac hypertrophy-related genes did not
      show any significant differences between the 50-Hz MF exposure group and the sham
      group. Taken together, in SD rats, exposure to a 50-Hz/100 MUT MF for 24 weeks
      did not show any obvious effects on the cardiovascular system.

PMID- 27694283
TI  - No adverse effects detected for simultaneous whole-body exposure to multiple
      frequency radiofrequency electromagnetic fields for rats in the intrauterine and
      pre- and post-weaning periods.
AB  - In everyday life, people are exposed to radiofrequency (RF) electromagnetic
      fields (EMFs) with multiple frequencies. To evaluate the possible adverse effects
      of multifrequency RF EMFs, we performed an experiment in which pregnant rats and
      their delivered offspring were simultaneously exposed to eight different
      communication signal EMFs (two of 800 MHz band, two of 2 GHz band, one of 2.4 GHz
      band, two of 2.5 GHz band and one of 5.2 GHz band). Thirty six pregnant Sprague
      Dawley (SD) 10-week-old rats were divided into three groups of 12 rats: one
      control (sham exposure) group and two experimental (low- and high-level RF EMF
      exposure) groups. The whole body of the mother rats was exposed to the RF EMFs
      for 20 h per day from Gestational Day 7 to weaning, and F1 offspring rats (46-48
      F1 pups per group) were then exposed up to 6 weeks of age also for 20 h per day.
      The parameters evaluated included the growth, gestational condition and organ
      weights of the dams; the survival rates, development, growth, physical and
      functional development, memory function, and reproductive ability of the F1
      offspring; and the embryotoxicity and teratogenicity in the F2 rats. No abnormal
      findings were observed in the dams or F1 offspring exposed to the RF EMFs or to
      the F2 offspring for any of the parameters evaluated. Thus, under the conditions
      of the present experiment, simultaneous whole-body exposure to eight different
      communication signal EMFs at frequencies between 800 MHz and 5.2 GHz did not show
      any adverse effects on pregnancy or on the development of rats.

PMID- 27694284
TI  - Biochemical, Physiological and Psychological Changes During Endurance Exercise in
      People With Type 1 Diabetes.
AB  - BACKGROUND: Increasing numbers of people with diabetes are adopting exercise
      programs. Fear of hypoglycemia, hypoglycemia itself, and injuries are major
      issues for many people with diabetes undertaking physical activity. The purpose
      of this study was to investigate the effects of type 1 diabetes mellitus on the
      risk of hypoglycemia, glycemic variability, exercise performance, changes in body
      composition, changes in insulin dosage, and psychosocial well-being during a
      multiday endurance exercise event. METHODS: Eleven participants (7 with type 1
      diabetes, 4 with normal glucose tolerance) undertook a 15-day, 2300 km cycling
      tour from Barcelona to Vienna. Data were prospectively collected using bike
      computers, continuous glucose monitors, body composition analyzers, and mood
      questionnaires. RESULTS: Mean blood glucose in riders with and without diabetes
      significantly reduced as the event progressed. Glycemic variability and time
      spent in hypoglycemia did not change throughout the ride for either set of
      riders. Riders with diabetes in the lowest quartile of sensor glucose values had
      significantly reduced power output. Percentage body fat also significantly fell.
      Hypo- and hyperglycemia provoked feelings of anxiety and worry. CONCLUSIONS: This
      is the first study to describe a real-time endurance event in type 1 diabetes,
      and provides important new data that cannot be studied in laboratory conditions.
      Hypoglycemia continues to occurs in spite of peer support and large reductions in
      insulin dose. Glycemic variability is shown as a potential barrier to
      participation in physical activity through effects on mood and psychological well
      being.

PMID- 27694286
TI  - Reliability, Validity, and Feasibility of Direct Elicitation of Children's
      Preferences for Health States.
AB  - BACKGROUND: Children's preferences for health states represent an important
      perspective when comparing the value of alternative health care interventions
      related to pediatric medicine, and are fundamental to comparative effectiveness
      research. However, there is debate over whether these preference data can be
      collected and used. PURPOSE: The purpose of this study was to establish
      psychometric properties of eliciting preferences for health states from children
      using direct methods. DATA SOURCES: Ovid Medline, PsycINFO, Scopus, EconLit.
      STUDY SELECTION: English studies, published after 1990, were identified using
      Medical Subject Headings or keywords. Results were reviewed to confirm that the
      study was based on: 1) a sample of children, and 2) preferences for health
      states. DATA EXTRACTION: Standardized data collection forms were used to record
      the preference elicitation method used, and any reported evidence regarding the
      validity, reliability, or feasibility of the method. DATA SYNTHESIS: Twenty-six
      studies were ultimately included in the analysis. The standard gamble and time
      tradeoff were the most commonly reported direct preference elicitation methods.
      Seven studies reported validity, four reported reliability, and nine reported
      feasibility. Of the validity reports, construct validity was assessed most often.
      Reliability reports typically involved interclass correlation coefficient. For
      feasibility, four studies reported completion rates. LIMITATIONS: The search was
      limited to four databases and restricted to English studies published after 1990.
      Only evidence available in published studies were considered; measurement
      properties may have been tested in pilot or pre-studies but were not published,
      and are not included in this review. CONCLUSION: The few studies found through
      this systematic review demonstrate that there is little empirical evidence on
      which to judge the use of direct preference elicitation methods with children
      regarding health states.

PMID- 27694287
TI  - Understanding Supportive Care Factors Among African American Breast Cancer
      Survivors.
AB  - INTRODUCTION: Comprehensive breast cancer care includes not only diagnosis,
      staging, and treatment of cancer but also assessment and management of the
      physical, psychological, social, and informational needs, collectively known as
      supportive care. Several studies have documented the importance of addressing
      supportive care factors among breast cancer survivors. However, there appears to
      be a paucity of research concerning African American breast cancer survivors
      (AABCS). Therefore, the purpose of this study was to describe and understand the
      patient-centered supportive care factors among self-identified AABCS. METHOD:
      Using a qualitative descriptive approach, an open-ended question explored
      supportive care factors that were used by N = 155 AABCS. RESULTS: Four supportive
      care factors were identified: faith, supportive structures, optimism, and access
      to information. DISCUSSION: An understanding of these factors might facilitate
      discussion between survivors and the health care team. The resultant effect could
      also inform and promote the delivery of culturally specific health care to
      address the supportive care needs among these women.

PMID- 27694288
TI  - "Perspectives" on Dental Education.

PMID- 27694285
TI  - APSA Awardee Submission: Tumor/cancer stem cell marker doublecortin-like kinase 1
      in liver diseases.
AB  - Liver diseases are the fourth leading cause of mortality among adults in the
      United States. Patients with chronic liver diseases such as viral hepatitis,
      fibrosis, and cirrhosis have significantly higher risks of developing
      hepatocellular carcinoma (HCC). With a dismal five-year survival rate of 11%, HCC
      is the third most common cause of cancer-related deaths worldwide. Regardless of
      the underlying cause, late presentation and a lack of effective therapy are the
      major impediments for successful treatment of HCC. Therefore, there is a
      considerable interest in developing new strategies for the prevention and
      treatment of chronic liver diseases at the early stages. Cancer stem cells
      (CSCs), a small cell subpopulation in a tumor, exhibit unlimited self-renewal and
      differentiation capacity. These cells are believed to play pivotal roles in the
      initiation, growth, metastasis, and drug-resistance of tumors. In this review, we
      will briefly discuss pivotal roles of the CSC marker doublecortin-like kinase 1
      (DCLK1) in hepatic tumorigenesis. Recent evidence suggests that anti-DCLK1
      strategies hold promising clinical potential for the treatment of cancers of the
      liver, pancreas, and colon.

PMID- 27694289
TI  - Preparing Dental Students and Residents to Overcome Internal and External
      Barriers to Evidence-Based Practice.
AB  - In recent years, evidence-based dentistry has become the ideal for research,
      academia, and clinical practice. However, barriers to implementation are many,
      including the complexity of interpreting conflicting evidence as well as
      difficulties in accessing it. Furthermore, many proponents of evidence-based care
      seem to assume that good evidence consistently exists and that clinicians can and
      will objectively evaluate data so as to apply the best evidence to individual
      patients' needs. The authors argue that these shortcomings may mislead many
      clinicians and that students should be adequately prepared to cope with some of
      the more complex issues surrounding evidence-based practice. Cognitive biases and
      heuristics shape every aspect of our lives, including our professional behavior.
      This article reviews literature from medicine, psychology, and behavioral
      economics to explore the barriers to implementing evidence-based dentistry.
      Internal factors include biases that affect clinical decision making: hindsight
      bias, optimism bias, survivor bias, and blind-spot bias. External factors include
      publication bias, corporate bias, and lack of transparency that may skew the
      available evidence in the peer-reviewed literature. Raising awareness of how
      these biases exert subtle influence on decision making and patient care can lead
      to a more nuanced discussion of addressing and overcoming barriers to evidence
      based practice.

PMID- 27694290
TI  - Improving a Dental School's Clinic Operations Using Lean Process Improvement.
AB  - The term "lean production," also known as "Lean," describes a process of
      operations management pioneered at the Toyota Motor Company that contributed
      significantly to the success of the company. Although developed by Toyota, the
      Lean process has been implemented at many other organizations, including those in
      health care, and should be considered by dental schools in evaluating their
      clinical operations. Lean combines engineering principles with operations
      management and improvement tools to optimize business and operating processes.
      One of the core concepts is relentless elimination of waste (non-value-added
      components of a process). Another key concept is utilization of individuals
      closest to the actual work to analyze and improve the process. When the medical
      center of the University of Kentucky adopted the Lean process for improving
      clinical operations, members of the College of Dentistry trained in the process
      applied the techniques to improve inefficient operations at the Walk-In Dental
      Clinic. The purpose of this project was to reduce patients' average in-the-door
      to-out-the-door time from over four hours to three hours within 90 days.
      Achievement of this goal was realized by streamlining patient flow and
      strategically relocating key phases of the process. This initiative resulted in
      patient benefits such as shortening average in-the-door-to-out-the-door time by
      over an hour, improving satisfaction by 21%, and reducing negative comments by
      24%, as well as providing opportunity to implement the electronic health record,
      improving teamwork, and enhancing educational experiences for students. These
      benefits were achieved while maintaining high-quality patient care with zero
      adverse outcomes during and two years following the process improvement project.

PMID- 27694292
TI  - Community-Based Dental Education Models: An Analysis of Current Practices at U.S.
      Dental Schools.
AB  - Community-based dental education (CBDE) enhances students' clinical expertise,
      improves their cultural competence, increases access to care, and fosters
      community engagement. As emphasis on CBDE has increased over the last decades,
      the aim of this survey study was to determine how CBDE is currently being
      implemented in U.S. dental schools. The study used a 20-item, author-designed
      survey emailed in April to August 2015 to 60 of the 65 U.S. dental schools,
      excluding those that had been recently established. Of the 60 schools,
      representatives of 33 responded, resulting in a 55% response rate: 70% public and
      30% private. These respondents reported that the extramural sites being used the
      most were community clinics (90.9%), Federally Qualified Health Clinics (66.7%),
      public health clinics (54.5%), and Indian Health Service clinics (42.4%). The
      majority of responding schools (63.6%) had ten or more sites available for
      rotations, and the rotation lengths were 1-2 weeks (29%), 2-4 weeks (25%), 4-6
      weeks (29%), 6-8 weeks (3.2%), and 8-10 weeks (12.9%). Most of the respondents
      (78.8%) reported that their students were unable to be assessed for clinical
      competencies at external clinical sites, but roughly half allowed students to
      receive clinical credit. After students completed their rotations, the majority
      of the respondents (81.8%) reported that students were required to produce a
      reflection, and 87.9% reported that students completed a post-rotation survey.
      Considering the benefits of CBDE for students' education and for improving access
      to oral health care, it is encouraging that over 45% of the responding schools
      required their students to spend four weeks or longer on external rotations.

PMID- 27694291
TI  - Predicting Rural Practice and Service to Indigent Patients: Survey of Dental
      Students Before and After Rural Community Rotations.
AB  - Community-based clinical rotations in rural areas expose dental students to
      diverse patient populations, practice models, and career opportunities as well as
      rural culture. The aims of this study at West Virginia University were to
      determine the best predictors of rural practice, assess the predictive validity
      of students' intention to practice in a rural area before and after their rural
      rotations, and evaluate the relationship between students' intention to practice
      in a rural area and intention to provide care for indigent patients. Online
      survey data were submitted pre- and post-rural clinical rotation by 432 of 489
      dental students over the study period 2001-12, yielding an 88% response rate. In
      2013, practice addresses from the West Virginia Board of Dentistry were added to
      the student database. The results showed that significant predictors of rural
      practice site were intended rural practice choice, rural hometown, and projected
      greater practice accessibility for indigent patients. The likelihood of students'
      predicting they would choose a rural practice increased after completion of their
      rural rotations. After the rotations, students predicted providing greater
      accessibility to indigent patients; these changes occurred for those who changed
      their predictions to rural practice choice after the rotations and those who
      subsequently entered rural practice. The dental students with a rural background
      or a greater service orientation were also more likely to expect to enter a rural
      practice and actually to do so after graduation. These findings suggest that
      dental school curricula that include rural rotations may increase students'
      sensitivity to issues of indigent patients and increase students' likelihood of
      rural practice choice.

PMID- 27694293
TI  - U.S. Dental Specialty Residents' Expectations and Anticipated Benefits of
      Academic Employment.
AB  - The aims of this study were to assess features of an academic career that dental
      specialty residents, as a group and by gender, find most attractive and to
      identify what determines their expectations for responsibilities and professional
      growth in academic employment. In November 2013, an invitation to participate in
      the study along with a link to an online survey was sent to the 407 U.S. program
      directors of six of the dental specialties (endodontics, oral and maxillofacial
      surgery, pediatric dentistry, periodontics, prosthodontics, and orthodontics),
      asking them to forward the survey to their residents. A total of 287 residents
      responded (112 [41.3%] female and 159 [58.7%] male) out of 4,400 enrolled in
      these specialty training programs (6.5% response rate). The female respondents
      were significantly more interested in joining academia than were the male
      respondents (female 48%; male 31.5%; p<0.005). Respondents of both genders were
      attracted to academic dentistry by opportunities for intellectual and
      professional stimulation, but the lifestyle of academicians was significantly
      more important for the female respondents. The most important feature of a
      successful academic career for the female respondents was the ability to have a
      good balance between career and personal life. While opportunity to conduct
      research was a positive feature for all residents interested in academia and both
      male and female respondents agreed strongly on the need for collaboration between
      faculty members for productive research, male respondents agreed significantly
      more than female respondents that faculty members should conduct independent
      research. Faculty members' feedback about academic employment were a
      significantly positive influence on those planning an academic career compared to
      those planning to enter private practice. This study found that the female and
      male residents differed in their expectations of responsibilities and
      professional growth in academic employment. These results may be useful for
      academic dental institutions and organizations when developing faculty
      recruitment and retention programs.

PMID- 27694295
TI  - Facilitating Dental Student Reflections: Using Mentor Groups to Discuss Clinical
      Experiences and Personal Development.
AB  - Despite the consensus on the importance of reflection for dental professionals, a
      lack of understanding remains about how students and clinicians should develop
      their ability to reflect. The aim of this study was to investigate dental
      students' and mentors' perceptions of mentor groups as an instructional method to
      facilitate students' reflection in terms of the strategy's learning potential,
      role of the mentor, group dynamics, and feasibility. At Ghent University in
      Belgium, third- and fourth-year dental students were encouraged to reflect on
      their clinical experiences and personal development in three reflective mentor
      sessions. No preparation or reports afterwards were required; students needed
      only to participate in the sessions. Sessions were guided by trained mentors to
      establish a safe environment, frame clinical discussions, and stimulate
      reflection. Students' and mentors' perceptions of the experience were assessed
      with a 17-statement questionnaire with response options on a five-point Likert
      scale (1=totally disagree to 5=totally agree). A total of 50 students and eight
      mentors completed the questionnaire (response rates 81% and 89%, respectively).
      Both students and mentors had neutral to positive perceptions concerning the
      learning potential, role of the mentor, group dynamics, and feasibility. The mean
      ideal total time for sessions in a year was 99 minutes (third-year students), 111
      minutes (fourth-year students), and 147 minutes (mentors). Reported reflective
      topics related to patient management, frustrations, and practice of dentistry.
      Overall mean appreciation for the experience ranged from 14.50 to 15.14 on the 20
      point scale. These findings about students' and mentors' positive perceptions of
      the experience suggest that mentor groups may be a potentially valuable strategy
      to promote dental students' reflection.

PMID- 27694294
TI  - Survey of Advanced Education in Prosthodontics Directors and Residents on
      Practices in Esthetic Dentistry.
AB  - The aim of this study was to determine the difference between the intended
      education by advanced education in prosthodontics (AEP) program directors and the
      perceived education received by AEP residents with respect to concepts of
      esthetic dentistry. Residents' confidence levels and current practices were also
      determined based on program level, with first- and second-year residents combined
      into "junior residents" and third- and fourth-year residents combined into
      "senior residents." Surveys were distributed to all U.S. and Canadian AEP program
      directors (N=52) in 2014 and residents (N=393) in 2015. The seven questions asked
      of directors and 20 asked of residents assessed resident training. The response
      rate for directors was 59.6% and for residents was 27.3%. Statistically
      significant results were found between the responding program directors'
      perceived education on esthetic principles and the responding residents'
      perceived education. The senior-level residents were more confident in each of
      the categories than residents at the junior level, although the difference was
      only significant for selecting porcelain systems to match inherent translucency,
      transfer of information to the laboratory, and surface staining or
      characterization. There was a difference between the program directors' intended
      teaching and the residents' perceptions with regards to bleaching, shade
      matching, selection of porcelain systems, transfer of information to the
      laboratory, and surface staining or characterization. The residents' confidence
      levels were higher at the senior level than those at the junior level in
      selecting porcelain systems, transfer of information to the laboratory, and
      staining/characterization. Faculty members in advanced prosthodontics programs
      may be able to use these findings to improve their residents' education in these
      areas.

PMID- 27694296
TI  - Quantifying Appointments, Treatment Time, Impressions, and Diagnostic Data of
      Cases Staffed by General Dentists and Prosthodontists in a Dental School Clinic.
AB  - The aim of this retrospective study was to quantify differences between general
      dentists and prosthodontists regarding appointments, treatment time, impressions,
      and preoperative diagnostic data in teaching predoctoral clinical fixed
      prosthodontics. Electronic dental records (n=356) of patients treated at one
      dental school in academic year 2012 were randomly selected for review to obtain
      the following data: faculty and student demographics, number of appointments and
      treatment time from preparation to cementation, number of impressions made,
      completion of oral disease control treatment (ODCT), and presence of preoperative
      periapical radiographs and diagnostic casts. The results showed that ODCT was
      completed in 78%, preoperative radiographs were present in 76%, and diagnostic
      casts made in 53% of the cases reviewed. There was no statistically significant
      difference in number of appointments, treatment time, or number of final
      impressions when students were staffed by general dentists or prosthodontists.
      When students were supervised by multiple faculty members, there was generally an
      increase in treatment time and number of appointments and final impressions.
      Although this study found no statistically significant differences between
      general dentists and prosthodontists regarding the criteria evaluated, the
      results suggest that faculty development and calibration are needed to ensure
      ODCT is completed and preoperative radiographs are present prior to initiating
      fixed prosthodontic procedures.

PMID- 27694297
TI  - Quality of Impressions and Work Authorizations Submitted by Dental Students
      Supervised by Prosthodontists and General Dentists.
AB  - Preclinical fixed prosthodontics is taught by Department of Prosthodontics
      faculty members at Virginia Commonwealth University School of Dentistry; however,
      86% of all clinical cases in academic year 2012 were staffed by faculty members
      from the Department of General Practice. The aims of this retrospective study
      were to quantify the quality of impressions, accuracy of laboratory work
      authorizations, and most common errors and to determine if there were differences
      between the rate of errors in cases supervised by the prosthodontists and the
      general dentists. A total of 346 Fixed Prosthodontic Laboratory Tracking Sheets
      for the 2012 academic year were reviewed. The results showed that, overall, 73%
      of submitted impressions were acceptable at initial evaluation, 16% had to be
      poured first and re-evaluated for quality prior to pindexing, 7% had multiple
      impressions submitted for transfer dies, and 4% were rejected for poor quality.
      There were higher acceptance rates for impressions and work authorizations for
      cases staffed by prosthodontists than by general dentists, but the differences
      were not statistically significant (p=0.0584 and p=0.0666, respectively).
      Regarding the work authorizations, 43% overall did not provide sufficient
      information or had technical errors that delayed prosthesis fabrication. The most
      common errors were incorrect mountings, absence of solid casts, inadequate
      description of margins for porcelain fused to metal crowns, inaccurate die
      trimming, and margin marking. The percentages of errors in cases supervised by
      general dentists and prosthodontists were similar for 17 of the 18 types of
      errors identified; only for margin description was the percentage of errors
      statistically significantly higher for general dentist-supervised than
      prosthodontist-supervised cases. These results highlighted the ongoing need for
      faculty development and calibration to ensure students receive the highest
      quality education from all faculty members teaching fixed prosthodontics.

PMID- 27694298
TI  - Psychometric Evaluation of a 13-Point Measure of Students' Overall Competence in
      Community-Based Dental Education Programs.
AB  - Since 2006, the University of Michigan School of Dentistry has used a 13-point
      measure of overall competence instrument to assess fourth-year dental students'
      end-rotation performance at community clinics. The aim of this study was to
      assess the reliability and validity of this instrument used by preceptors to rate
      students' overall competence during community-based dental education experiences.
      The measure was analyzed using performance ratings for all fourth-year DDS
      students in the graduating classes of 2012 and 2013 (combined n=201). The results
      were that interrater agreement was satisfactory and the measure scored high for
      internal consistency; also, the measure loaded highly on a single overall
      competence factor. Ratings on this measure did not correlate with students' final
      cumulative dental school GPA, but showed a significant positive correlation with
      their fourth-year fall patient management grades (which signify students'
      conscientiousness in managing patients and their families in a professional and
      ethical manner). There were differences in grading systems between the 2012
      cohort (which used a pass/fail system) and the 2013 cohort (which used a letter
      grade system) and the mean ratings they received (higher for the 2013 cohort).
      Overall, the study found that the 13-point measure demonstrated excellent
      reliability and validity, suggesting it is useful in determining a student's
      clinical competence in these settings.

PMID- 27694299
TI  - Developing and Testing the Short-Form Knowledge, Efficacy, and Practices
      Instrument for Assessing Cultural Competence.
AB  - The importance of educating dental students in cultural competence has been
      widely emphasized, but there is a need to assess cultural competence in a
      consistent and reliable way. The aims of this study were to determine latent
      constructs for the initial measure of cultural competence for oral health
      providers, the Knowledge, Efficacy, and Practices Instrument (KEPI), and to
      determine how well these factors related to previously identified latent
      constructs. Data were collected in surveys of dental students and from dental
      hygiene, dental assisting, and dental faculty members in 44 academic dental
      institutions from 2012 to 2015. There were a total of 1,786 respondents to the
      surveys; response rates to individual surveys ranged from 35% to 100%. There were
      982 (55%) female and 804 (45%) male respondents, 286 (16%) underrepresented
      minority (URM) and 1,500 (84%) non-URM respondents, and 339 (19%) faculty and
      1,447 (81%) student respondents. Three latent constructs were identified. Female
      respondents scored significantly higher on the culture-centered practice and
      efficacy of assessment factors, while URM respondents had significantly higher
      scores on all three of the KEPI factors. Measurements indicated that the long
      form KEPI could be shortened by ten questions and still have three meaningful
      measurements. Continued research in assessing other health care providers'
      cultural competence is needed to expand the KEPI to measure providers' cultural
      competence with patients with minority sexual orientation and gender identity
      issues and those with physical disabilities, mental illness, and autism to
      advance patient-centric communication.

PMID- 27694301
TI  - Peer Education: Reviews of the Literature (PERLs).

PMID- 27694300
TI  - Evaluating the Impact of Releasing an Item Pool on a Test's Empirical
      Characteristics.
AB  - Protecting the security of examination questions is an important task for high
      stakes examining boards/agencies and university programs. To maintain the
      security of questions, examining boards and university programs use a combination
      of prevention, detection, and enforcement strategies. A common prevention
      strategy is to establish a number of controls on access to questions; however,
      restricting access can motivate examinees to try harder to reconstruct questions
      that may appear on future versions of the test. Moreover, access to study
      materials by some groups and not others can present a challenge to the fairness
      of examinations. The aim of this study was to evaluate the empirical stability of
      test characteristics. Specifically, the primary research objective was to
      investigate the empirical stability of the items and test forms of a written
      examination before and after a specific policy decision was implemented. As a
      response to both of these concerns, this article describes a study that evaluated
      how psychometric (i.e., statistical) properties of test forms and individual
      questions might be affected by publicly releasing a larger number of questions
      from an item question pool. A series of analyses were conducted, including item
      drift to evaluate stability of the characteristics. The results suggest that
      empirical characteristics of the test forms and individual questions have
      remained relatively stable since the release policy was implemented.
      Specifically, statistical properties of the test forms have continued to perform
      similarly to test forms that were constructed prior to the release. Although the
      results of this study were promising, the context of this specific testing
      program may have offered additional protections such as a limited number of
      administrations that others may not. Therefore, testing/examining agencies and
      university programs may want to consider this strategy with appropriate caution.

PMID- 27694302
TI  - Combination of Open Subtotal Calcanectomy and Stabilization With External
      Fixation as Limb Salvage Procedure in Hindfoot-Infected Diabetic Foot Ulcers.
AB  - Diabetic hindfoot ulcers, complicated by osteomyelitis, are associated with a
      high risk of major amputation. Partial calcanectomy, preceded by an effective
      management of the infection and of the eventual peripheral artery disease, can be
      considered as valid therapeutic option. We have evaluated a therapeutic protocol
      for diabetic hindfoot ulcers complicated by osteomyelitis, which, besides an
      adequate surgical debridement, considers a reconstructive pathway assisted by the
      positioning of a circular external fixator. We made a prospective study of a
      cohort of diabetic patients affected by heel ulcer complicated by osteomyelitis.
      All patients underwent open partial calcanectomy associated with the positioning
      of a circular external frame specifically designed for hindfoot stabilization and
      offloading. A reconstructive procedure was implemented starting with the
      application of negative pressure wound therapy and coverage with dermal
      substitute and split thickness skin grafting. From November 2014 to November
      2015, 18 consecutive patients were enrolled. Mean follow-up period was 212.3 +/-
      64.0 days. Healing was achieved in 18 (100%) patients. The mean healing time was
      69.0 +/- 64.0 days. No major amputation had to be performed during the follow-up.
      Open partial calcanectomy associated with external fixation and skin
      reconstruction was as efficient as limb salvage in patients with infected lesions
      of the hindfoot complicated by calcaneal osteomyelitis.

PMID- 27694303
TI  - Validation of a Screening Questionnaire for Chronic Leg Ulcers.
AB  - The use of a validated screening questionnaire to identify individuals with
      chronic leg ulcers allows large-scale population-based studies to be conducted
      that measure and monitor the prevalence of the disease. The aim of this study was
      to design and validate such a screening questionnaire to identify patients with
      chronic leg ulcers. A simple 3-item questionnaire was developed at the Department
      of Dermatology, University Hospital of Zealand, Denmark. In total, 90 patients
      attending the department's outpatient clinic for dermatological diseases and
      chronic wounds were included in this study. All included participants completed
      the questionnaire and were subsequently examined by dermatologists. We found that
      the constructed 3-item questionnaire in this study had a sensitivity and
      specificity of 95% and 93% and a positive predictive value and negative
      predictive value of 78% and 95%, respectively. Moreover, we found that the use of
      the 3-item questionnaire, as compared with a single question, in which the
      participants were asked whether they currently have a leg ulcer, resulted in
      significantly higher positive predictive value (+11.6%, P = .035) and specificity
      (+5.6%, P = .046) of the diagnostic test. Future studies are merited to
      investigate the diagnostic accuracy of the questionnaire in other populations and
      settings.

PMID- 27694304
TI  - Preoperative Angiographic Criteria for Predicting Free-Flap Transfer Outcomes in
      Patients With Lower-Extremity Peripheral Arterial Disease.
AB  - Patients scheduled for microsurgical reconstruction of the lower leg often
      receive preoperative assessment of recipient vessels using angiography. However,
      no clear standard is available for evaluating angiographic results to predict
      free-flap survival outcomes. We developed angiographic criteria for predicting
      surgical outcome in patients with lower-extremity peripheral arterial disease
      based on abnormality of the anterior tibial and posterior tibial arteries. We
      applied the criteria to a small number of patients scheduled for microsurgical
      reconstruction of the lower leg. Angiographies with arterial abnormalities were
      classified into 3 groups: favorable free-flap survival, compromised free-flap
      survival, and postsurgical pedal ischemia. The study enrolled 50 patients between
      2005 and 2013. In 42% of patients, arterial abnormalities were observed by
      angiography. Age >65 years was the strongest risk factor for development of lower
      leg arterial abnormality ( P < .001). The anterior tibial and peroneal arteries
      were significantly more stenotic than other vessels. In the favorable free-flap
      survival and compromised free-flap survival groups, free-flap transfers were
      attempted in 7 patients but intraoperatively abandoned in 2 patients, with
      postoperative failure in 1 patient. In the postsurgical pedal ischemia group,
      free-flap transfers were attempted in 10 patients but intraoperatively abandoned
      in 6 patients, with postoperative failure in 3.

PMID- 27694305
TI  - In vitro germ cell differentiation from embryonic stem cells of mice: induction
      control by BMP4 signalling.
AB  - The present study aims to confirm and analyse germ cell-related patterns and
      specific gene expressions at a very early stage of cell commitment. Following the
      XY cytogenetic confirmation of the CCE mouse embryonic stem cells (mESCs) line,
      cells were cultured to form embryoid bodies (EBs). Expression pattern assessment
      of the mouse vasa homologue (Mvh), Stra8, alpha6 and beta1 integrin genes in ESC
      and 1-3-day-old EB showed that all genes except alpha6 integrin were expressed in
      the ESC. The mean calibration of Mvh, Stra8 and alpha6 integrin expression
      significantly increased upon EB formation compared with the ESCs. During mouse
      embryogenesis, the signalling of bone morphogenetic protein (BMP) is essential
      for germ-line formation. To investigate its role in germ-line induction in vitro,
      mESCs were cultured as 1-day-old EB aggregates with BMP4 for 4 days in STO co
      culture systems, in the presence and absence of 5 ng/ml BMP4. At the end of the
      culture period, colony assay (number and diameter) was performed and the
      viability percentage and proliferation rate was determined. There were no
      significant statistical differences in the abovementioned criteria between these
      two groups. Moreover, the expression of Mvh, alpha6 and beta1 integrins, Stra8
      and Piwil2 genes was evaluated in co-culture groups. The molecular results of co
      culture groups showed higher-but insignificant-Piwil2 and significant alpha6
      integrin expressions in BMP4 treated co-culture systems. These results confirmed
      that the EB system and the presence of BMP4 in a STO co-culture system improve
      the differentiation of ESCs to germ cell.

PMID- 27694306
TI  - Mycophenolic Acid-Induced Developmental Defects in Zebrafish Embryos.
AB  - With the increasing use of mycophenolic acid (MPA) in solid organ
      transplantation, some clinical studies indicate that it is also a human
      teratogen. However, it is unknown by which mechanism MPA acts as a teratogen.
      Mycophenolic acid was a selective blocker of de novo purine synthesis, and its
      immunosuppressive effect is mediated by the inhibition of inosine monophosphate
      dehydrogenase, which could be a target for MPA-induced toxicity as well. The aim
      of our study was to examine the direct influence of MPA exposure on zebrafish
      (Danio rerio) embryos. Morphological defects including tail curvature and severe
      pericardial edema in zebrafish embryos caused by MPA (3.7-11.1 umol/L) were found
      in a dose-dependent manner. The teratogenic index (25% lethal concentration value
      (LC25)/no observed adverse effect level ratio) was 16, which indicated MPA as a
      teratogen. Quantitative polymerase chain reaction analysis revealed that the
      expression level of impdh1b and impdh2 was significantly reduced by MPA treatment
      at 8 umol/L (equals to LC25 level). All the toxic effects could be partially
      reversed by the addition of 33.3 umol/L guanosine. Our results indicated that MPA
      impairs the development of zebrafish embryos via inhibition of impdh activity,
      which subsequently caused a guanosine nucleotide depletion in vivo.

PMID- 27694308
TI  - Analyzing structure-function relationships of artificial and cancer-associated
      PARP1 variants by reconstituting TALEN-generated HeLa PARP1 knock-out cells.
AB  - Genotoxic stress activates PARP1, resulting in the post-translational
      modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted
      PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via
      TALEN-mediated gene targeting. After comprehensive characterization of these
      cells during genotoxic stress, we analyzed structure-function relationships of
      PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly,
      we verified that the PARP1?E988K mutant exhibits mono-ADP-ribosylation activity
      and we demonstrate that the PARP1?L713F mutant is constitutively active in cells.
      Secondly, both mutants exhibit distinct recruitment kinetics to sites of laser
      induced DNA damage, which can potentially be attributed to non-covalent PARP1-PAR
      interaction via several PAR binding motifs. Thirdly, both mutants had distinct
      functional consequences in cellular patho-physiology, i.e. PARP1?L713F expression
      triggered apoptosis, whereas PARP1?E988K reconstitution caused a DNA-damage
      induced G2 arrest. Importantly, both effects could be rescued by PARP inhibitor
      treatment, indicating distinct cellular consequences of constitutive PARylation
      and mono(ADP-ribosyl)ation. Finally, we demonstrate that the cancer-associated
      PARP1 SNP variant (V762A) as well as a newly identified inherited PARP1 mutation
      (F304L?V762A) present in a patient with pediatric colorectal carcinoma exhibit
      altered biochemical and cellular properties, thereby potentially supporting human
      carcinogenesis. Together, we establish a novel cellular model for PARylation
      research, by revealing strong structure-function relationships of natural and
      artificial PARP1 variants.

PMID- 27694307
TI  - Distribution and effects of amino acid changes in drug-resistant alpha and beta
      herpesviruses DNA polymerase.
AB  - Emergence of drug-resistance to all FDA-approved antiherpesvirus agents is an
      increasing concern in immunocompromised patients. Herpesvirus DNA polymerase
      (DNApol) is currently the target of nucleos(t)ide analogue-based therapy.
      Mutations in DNApol that confer resistance arose in immunocompromised patients
      infected with herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV),
      and to lesser extent in herpes simplex virus 2 (HSV-2), varicella zoster virus
      (VZV) and human herpesvirus 6 (HHV-6). In this review, we present distinct drug
      resistant mutational profiles of herpesvirus DNApol. The impact of specific
      DNApol amino acid changes on drug-resistance is discussed. The pattern of genetic
      variability related to drug-resistance differs among the herpesviruses. Two
      mutational profiles appeared: one favoring amino acid changes in the Palm and
      Finger domains of DNApol (in alpha-herpesviruses HSV-1, HSV-2 and VZV), and
      another with mutations preferentially in the 3'-5' exonuclease domain (in beta
      herpesvirus HCMV and HHV-6). The mutational profile was also related to the class
      of compound to which drug-resistance emerged.

PMID- 27694309
TI  - Activation of cGAS-dependent antiviral responses by DNA intercalating agents.
AB  - Acridine dyes, including proflavine and acriflavine, were commonly used as
      antiseptics before the advent of penicillins in the mid-1940s. While their mode
      of action on pathogens was originally attributed to their DNA intercalating
      activity, work in the early 1970s suggested involvement of the host immune
      responses, characterized by induction of interferon (IFN)-like activities through
      an unknown mechanism. We demonstrate here that sub-toxic concentrations of a
      mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase
      (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of
      these compounds to induce low level DNA damage and cytoplasmic DNA leakage,
      resulting in cGAS-dependent cGAMP-like activity. Critically,
      acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells
      significantly reduced rhinovirus infection. Collectively, our findings constitute
      the first evidence that non-toxic DNA binding agents have the capacity to act as
      indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells.

PMID- 27694311
TI  - Infomap Bioregions: Interactive Mapping of Biogeographical Regions from Species
      Distributions.
AB  - Biogeographical regions (bioregions) reveal how different sets of species are
      spatially grouped and therefore are important units for conservation, historical
      biogeography, ecology, and evolution. Several methods have been developed to
      identify bioregions based on species distribution data rather than expert
      opinion. One approach successfully applies network theory to simplify and
      highlight the underlying structure in species distributions. However, this method
      lacks tools for simple and efficient analysis. Here, we present Infomap
      Bioregions, an interactive web application that inputs species distribution data
      and generates bioregion maps. Species distributions may be provided as
      georeferenced point occurrences or range maps, and can be of local, regional, or
      global scale. The application uses a novel adaptive resolution method to make
      best use of often incomplete species distribution data. The results can be
      downloaded as vector graphics, shapefiles, or in table format. We validate the
      tool by processing large data sets of publicly available species distribution
      data of the world's amphibians using species ranges, and mammals using point
      occurrences. We then calculate the fit between the inferred bioregions and WWF
      ecoregions. As examples of applications, researchers can reconstruct ancestral
      ranges in historical biogeography or identify indicator species for targeted
      conservation. [Biogeography; bioregionalization; conservation; mapping].

PMID- 27694310
TI  - Flexible expressed region analysis for RNA-seq with derfinder.
AB  - Differential expression analysis of RNA sequencing (RNA-seq) data typically
      relies on reconstructing transcripts or counting reads that overlap known gene
      structures. We previously introduced an intermediate statistical approach called
      differentially expressed region (DER) finder that seeks to identify contiguous
      regions of the genome showing differential expression signal at single base
      resolution without relying on existing annotation or potentially inaccurate
      transcript assembly.We present the derfinder software that improves our
      annotation-agnostic approach to RNA-seq analysis by: (i) implementing a
      computationally efficient bump-hunting approach to identify DERs that permits
      genome-scale analyses in a large number of samples, (ii) introducing a flexible
      statistical modeling framework, including multi-group and time-course analyses
      and (iii) introducing a new set of data visualizations for expressed region
      analysis. We apply this approach to public RNA-seq data from the Genotype-Tissue
      Expression (GTEx) project and BrainSpan project to show that derfinder permits
      the analysis of hundreds of samples at base resolution in R, identifies
      expression outside of known gene boundaries and can be used to visualize
      expressed regions at base-resolution. In simulations, our base resolution
      approaches enable discovery in the presence of incomplete annotation and is
      nearly as powerful as feature-level methods when the annotation is
      complete.derfinder analysis using expressed region-level and single base-level
      approaches provides a compromise between full transcript reconstruction and
      feature-level analysis. The package is available from Bioconductor at
      www.bioconductor.org/packages/derfinder.

PMID- 27694312
TI  - Performance of short ECG recordings twice daily to detect paroxysmal atrial
      fibrillation in stroke and transient ischemic attack patients.
AB  - Aims Prolonged cardiac monitoring after stroke is recommended though there is no
      consensus on optimal methods. Short-term ECG recordings with a "thumb-ECG" device
      have shown promising preliminary results regarding effectiveness and cost
      benefit. We aimed to examine the performance of thumb-ECG and five days' Holter
      monitoring in a prospective trial. A secondary endpoint was the inter-observer
      agreement of the thumb-ECG. Methods Patients older than 65 years with no history
      of atrial fibrillation who suffered an acute stroke or transient ischemic attack
      of unknown origin were prospectively included. Patients were monitored for atrial
      fibrillation with five days' Holter and concurrent 30 s thumb-ECG twice daily,
      the latter continuing for 30 days. Inter-observer agreement for the thumb-ECG was
      determined. Results One hundred patients were included and 95 patients were
      analyzed. Paroxysmal atrial fibrillation was diagnosed in 20 patients with the
      thumb-ECG recordings and 17 patients on the Holter monitoring. Only 10 were
      diagnosed with both methods. The difference between the detection rates of the
      two devices was not significant ( p = 0.63). The inter-observer agreement of the
      thumb-ECG had a kappa value of 0.65. Conclusion Thirty days' thumb-ECG recordings
      twice daily for 30 s detect a high proportion of paroxysmal atrial fibrillation
      in a stroke or transient ischemic attack cohort. The proportion was comparable to
      five days' Holter monitoring but the agreement between the two methods was poor
      and the trial was not powered to detect a minor difference between the devices.
      The inter-observer agreement for the thumb-ECG was substantial.
      www.clinicalTrials.gov UI: NCT02261766.

PMID- 27694314
TI  - Changes in stroke incidence, outcome, and associated factors in Porto between
      1998 and 2011.
AB  - Objective Year 2000 marked a turning point in stroke prevention and treatment in
      Portugal. In face of high incidence rates stroke awareness campaigns, close
      surveillance of vascular risk factors and implementation of hospital stroke units
      were advanced by the National Health Authorities. To understand the effect of
      such measures, we assessed changes in stroke incidence and short-term outcome
      using data from two community-based registers undertaken in Porto in 1998-2000
      and 2009-2011. Methods We used standard diagnostic criteria and multiple
      overlapping sources of case-ascertainment for first-ever strokes. Short-term
      outcome was measured by the modified Rankin Scale; disabling stroke was defined
      whenever post-stroke mRS score>pre-stroke mRS and >1. Results Globally, 462 and
      405 first-ever stroke cases were registered in 1998-2000 and 2009-2011,
      respectively. Stroke incidence decreased by 23%, from 261 to 203/100,000 after
      adjustment for the Portuguese population. Significant reduction was found in
      those aged <75 years (31%) and in women (32%). Incidence of disabling strokes was
      reduced by 29%. Fatal strokes decreased by 46%, while intracerebral hemorrhage
      decreased by 51%. Risk of disability from stroke decreased by 11% (RR = 0.89;
      95%CI, 0.81-0.98) in 2009-2011, as found after adjusting for patient/stroke
      characteristics in a Poisson model. Moreover, when patients arrived hospital
      within 3 h from stroke onset, the risk of disabling stroke was 0.76 (95%CI, 0.67
      0.87) in 2009-2011 vs. 1998-2000, compared to 1.03 (95%CI, 0.89-1.12) for late
      arrival. Conclusion Risk of stroke, mainly of hemorrhagic stroke, was
      substantially reduced over time. Timely action in acute phase was responsible for
      the decline in disability across periods.

PMID- 27694313
TI  - Stroke Epidemiology in an Australian Rural Cohort (SEARCH).
AB  - Background Stroke rates in Australia and New Zealand have been declining since
      1990 but all studies have been completed in large urban centers. Aim We report
      the first Australasian stroke incidence study in a rural population. Methods The
      authors applied the principle of complete ascertainment, used the WHO standard
      definition of stroke and classified ischemic stroke by the TOAST criteria. Data
      were collected from five rural centers defined by postcode of residence, over a 2
      year period with 12 months of follow up of all cases. Results There were 217
      strokes in 215 individuals in a population of 96,036 people, over 2 years, giving
      a crude attack rate of 113 per 100,000 per year. The 181 first-ever strokes (83%
      of total), standardized to the WHO world population, occurred at a rate of
      50/100,000 (95% CI: 43-58). The 28-day fatality for first-ever strokes was 24%
      (95% CI: 18-31) and 77% (95% CI: 71-83) were classified as ischemic (140/181),
      15% (95% CI: 10-21) intracerebral hemorrhage, 3% (95% CI: 1-6) due to
      subarachnoid hemorrhage and 5% (95% CI: 2-9) were unknown. A high proportion of
      first-ever ischemic strokes (44%) were cardioembolic, mostly (77%) due to atrial
      arrhythmias. Of the 38 with known atrial arrhythmias prior to stroke, only six
      (16%) were therapeutically anticoagulated. Conclusions This rural companion study
      of a recent Australian urban stroke incidence study confirms the downward trend
      of stroke incidence in Australia, and reiterates that inadequate anticoagulation
      of atrial arrhythmia remains a preventable cause of ischemic stroke.

PMID- 27694316
TI  - Visit to Thailand.

PMID- 27694317
TI  - Endocarditis: the great mimic of rheumatic diseases.
AB  - Rheumatic manifestations may be prevalent in more than 30% of patients with
      infective endocarditis (IE), often predating this diagnosis by several months. A
      case series of five patients recorded at a tertiary care Rheumatology and
      Clinical Immunology unit over a period of 1 year emphasises that varied
      presentations of endocarditis may mimic uncommon rheumatic diseases.

PMID- 27694315
TI  - Thrombolysis and thrombectomy in patients treated with dabigatran with acute
      ischemic stroke: Expert opinion.
AB  - Systemic thrombolysis with rt-PA is contraindicated in patients with acute
      ischemic stroke anticoagulated with dabigatran. This expert opinion provides
      guidance on the use of the specific reversal agent idarucizumab followed by rt-PA
      and/or thrombectomy in patients with ischemic stroke pre-treated with dabigatran.
      The use of idarucizumab followed by rt-PA is covered by the label of both drugs.

PMID- 27694319
TI  - Metamizole (dipyrone) effects on sevoflurane requirements and postoperative
      hyperalgesia in rats.
AB  - Unlike non-steroidal anti-inflammatory drugs (NSAIDs), metamizole has poor anti
      inflammatory effects; and is suitable for models where analgesia, but not anti
      inflammatory effects, is desirable. Like opioids, these drugs produce
      perioperative analgesia while reducing anaesthetic requirements, but it remains
      unclear whether they may develop tolerance or hyperalgesia, and thus decrease in
      analgesic efficacy. The aim was to determine whether tolerance or hyperalgesia to
      metamizole occurred in rats, and whether the sevoflurane minimum alveolar
      concentration (MAC) was affected. In a randomized, prospective, controlled study,
      male Wistar rats ( n = 8 per group) were administered metamizole (300 mg/kg, day
      4). Previously, the following treatments were provided: daily metamizole for four
      days (0-3), morphine (10 mg/kg; positive control, day 0 only) or saline (negative
      control). The main outcome measures were mechanical (MNT) and warm thermal (WNT)
      nociceptive quantitative sensory thresholds. The baseline sevoflurane MAC and the
      reduction produced by the treatments were also determined. The mean (SD) baseline
      MAC [2.4(0.2)%vol] was decreased by morphine and metamizole by 45(11)% and 33(7)%
      ( P = 0.000, both), respectively. Baseline MNT [35.4(4.5) g] and WNT [13.2(2.4)
      s] were decreased by morphine and metamizole: MNT reduction of 22(6)% ( P =
      0.000) and 22(7)% ( P = 0.001), respectively and WNT reduction of 34(14)% ( P =
      0.000) and 24(13)% ( P = 0.001). The baseline MAC on day 4 was neither modified
      by treatments nor the MAC reduction produced by metamizole (days 0 and 4; P >
      0.05). In conclusion, repeated metamizole administration may produce
      hyperalgesia, although it may not modify its anaesthetic sparing effect. The
      clinical relevance of this effect in painful research models requiring prolonged
      analgesic therapy warrants further investigation.

PMID- 27694318
TI  - Ventral striatum and amygdala activity as convergence sites for early adversity
      and conduct disorder.
AB  - Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and
      has been associated with alterations in regions of affective processing like
      ventral striatum (VS) and amygdala. However, no study so far has demonstrated
      neural converging effects of CFA and CD in the same sample. At age 25 years,
      functional MRI data during two affective tasks, i.e. a reward (N = 171) and a
      face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in
      right-handed currently healthy participants of an epidemiological study followed
      since birth. CFA during childhood was determined using a standardized parent
      interview. Disruptive behaviors and CD diagnoses during childhood and adolescence
      were obtained by diagnostic interview (2-19 years), temperamental reward
      dependence was assessed by questionnaire (15 and 19 years).CFA predicted
      increased CD and amygdala volume. Both exposure to CFA and CD were associated
      with a decreased VS response during reward anticipation and blunted amygdala
      activity during face-matching. CD mediated the effect of CFA on brain activity.
      Temperamental reward dependence was negatively correlated with CFA and CD and
      positively with VS activity. These findings underline the detrimental effects of
      CFA on the offspring's affective processing and support the importance of early
      postnatal intervention programs aiming to reduce childhood adversity factors.

PMID- 27694320
TI  - Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments
      its plasminogen activator activity.
AB  - Activated factor XII (FXIIa) has plasminogen activator capacity but its relative
      contribution to fibrinolysis is considered marginal compared with urokinase and
      tissue plasminogen activator. Polyphosphate (polyP) is released from activated
      platelets and mediates FXII activation. Here, we investigate the contribution of
      polyP to the plasminogen activator function of alphaFXIIa. We show that both
      polyP70, of the chain length found in platelets (60-100 mer), and platelet
      derived polyP significantly augment the plasminogen activation capacity of
      alphaFXIIa. PolyP70 stimulated the autoactivation of FXII and subsequent
      plasminogen activation, indicating that once activated, alphaFXIIa remains bound
      to polyP70 Indeed, complex formation between polyP70 and alphaFXIIa provides
      protection against autodegradation. Plasminogen activation by betaFXIIa was
      minimal and not enhanced by polyP70, highlighting the importance of the anion
      binding site. PolyP70 did not modulate plasmin activity but stimulated activation
      of Glu and Lys forms of plasminogen by alphaFXIIa. Accordingly, polyP70 was found
      to bind to FXII, alphaFXIIa, and plasminogen, but not betaFXIIa. Fibrin and
      polyP70 acted synergistically to enhance alphaFXIIa-mediated plasminogen
      activation. The plasminogen activator activity of the alphaFXIIa-polyP70 complex
      was modulated by C1 inhibitor and histidine-rich glycoprotein, but not
      plasminogen activator inhibitors 1 and 2. Platelet polyP and FXII were found to
      colocalize on the activated platelet membrane in a fibrin-dependent manner and
      decorated fibrin strands extending from platelet aggregates. We show that in the
      presence of platelet polyP and the downstream substrate fibrin, alphaFXIIa is a
      highly efficient and favorable plasminogen activator. Our data are the first to
      document a profibrinolytic function of platelet polyP.

PMID- 27694322
TI  - Hedgehog pathway activation in T-cell acute lymphoblastic leukemia predicts
      response to SMO and GLI1 inhibitors.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive childhood leukemia
      that is caused by the accumulation of multiple genomic lesions resulting in
      transcriptional deregulation and increased cell proliferation and survival.
      Through analysis of gene expression data, we provide evidence that the hedgehog
      pathway is activated in 20% of T-ALL samples. Hedgehog pathway activation is
      associated with ectopic expression of the hedgehog ligands Sonic hedgehog (SHH)
      or Indian hedgehog (IHH), and with upregulation of the transcription factor GLI1
      Ectopic expression of SHH or IHH in mouse T cells in vivo caused hedgehog pathway
      activation in both lymphoid and epithelial cells in the thymus and resulted in
      increased expression of important T-cell stimulatory ligands (Dll4, Il7, and
      Vegf) by thymic epithelial cells. In T-ALL cell lines, pharmacological inhibition
      or short interfering RNA-mediated knockdown of SMO or GLI1 led to decreased cell
      proliferation. Moreover, primary T-ALL cases with high GLI1 messenger RNA levels,
      but not those with low or undetectable GLI1 expression, were sensitive to
      hedgehog pathway inhibition by GANT61 or GDC-0449 (vismodegib) using ex vivo
      cultures and in vivo xenograft models. We identify the hedgehog pathway as a
      novel therapeutic target in T-ALL and demonstrate that hedgehog inhibitors
      approved by the US Food and Drug Administration could be used for the treatment
      of this rare leukemia.

PMID- 27694321
TI  - Inverse agonism at the P2Y12 receptor and ENT1 transporter blockade contribute to
      platelet inhibition by ticagrelor.
AB  - Ticagrelor is a potent antagonist of the P2Y12 receptor (P2Y12R) and consequently
      an inhibitor of platelet activity effective in the treatment of atherothrombosis.
      Here, we sought to further characterize its molecular mechanism of action.
      Initial studies showed that ticagrelor promoted a greater inhibition of adenosine
      5'-diphosphate (ADP)-induced Ca2+ release in washed platelets vs other P2Y12R
      antagonists. This additional effect of ticagrelor beyond P2Y12R antagonism was in
      part as a consequence of ticagrelor inhibiting the equilibrative nucleoside
      transporter 1 (ENT1) on platelets, leading to accumulation of extracellular
      adenosine and activation of Gs-coupled adenosine A2A receptors. This contributed
      to an increase in basal cyclic adenosine monophosphate (cAMP) and vasodilator
      stimulated phosphoprotein phosphorylation (VASP-P). In addition, ticagrelor
      increased platelet cAMP and VASP-P in the absence of ADP in an adenosine receptor
      independent manner. We hypothesized that this increase originated from a direct
      effect on basal agonist-independent P2Y12R signaling, and this was validated in
      1321N1 cells stably transfected with human P2Y12R. In these cells, ticagrelor
      blocked the constitutive agonist-independent activity of the P2Y12R, limiting
      basal Gi-coupled signaling and thereby increasing cAMP levels. These data suggest
      that ticagrelor has the pharmacological profile of an inverse agonist. Based on
      our results showing insurmountable inhibition of ADP-induced Ca2+ release and
      forskolin-induced cAMP, the mode of antagonism of ticagrelor also appears
      noncompetitive, at least functionally. In summary, our studies describe 2 novel
      modes of action of ticagrelor, inhibition of platelet ENT1 and inverse agonism at
      the P2Y12R that contribute to its effective inhibition of platelet activation.

PMID- 27694323
TI  - Interactions between Gastrointestinal Nematodes and Malaria in a Cohort of
      Children in an Amazonian Village.
AB  - INTRODUCTION: Most studies on nematode-malaria interactions were conducted
      outside of the Americas. The objective of the present study was thus to study the
      relation between malaria and nematodes in a cohort of children in an Amazonian
      village. METHODS: Odds ratios for intestinal nematode infections as an
      explanatory variable to malaria resistant vs. malaria sensitive were computed.
      RESULTS: Ascaris lumbricoides was significantly more frequent in the 'resistant'
      malaria group than in the 'sensitive' one. CONCLUSIONS: Despite its low
      statistical power, the present results find that Ascaris was associated with less
      malaria, as observed by a number of studies.

PMID- 27694324
TI  - Racial Difference in Symptom Onset to Door Time in ST Elevation Myocardial
      Infarction.
AB  - BACKGROUND: There are poorer outcomes following ST elevation myocardial
      infarction in blacks compared to white patients despite comparable door-to
      reperfusion time. We hypothesized that delays to hospital presentation may be
      contributory. METHODS AND RESULTS: We conducted a retrospective analysis of the
      1144 patients admitted for STEMI in our institution from 2008 to 2013. The door
      to-balloon time (D2BT) and symptom-onset-to-door time (SODT) were compared by
      race. Bivariate analysis was done comparing the median D2BT and SODT. Stratified
      analyses were done to evaluate the effect of race on D2BT and SODT, accounting
      for insurance status, age, sex and comorbidities. The mean age was 59+/-13 years;
      56% of this population was black and 41% was white. Males accounted for 66% of
      this population. The median D2BT was 60 minutes (interquartile range [IQR] 42
      82), and median SODT was 120 minutes (IQR 60-720). There was no significant
      difference in D2BT by race (P=0.86). Black patients presented to the emergency
      room (ER) later than whites (SODT=180 [IQR 60-1400] vs 120 [IQR 60-560] minutes,
      P<0.01) and were more likely to be uninsured (P<0.01). After controlling for
      comorbidities, insurance, and socioeconomic status, blacks were 60% more likely
      to present late after a STEMI (OR 1.6, P<0.01). A subset analysis excluding
      transferred patients showed similar results. CONCLUSIONS: Black patients present
      later to the ER after STEMI with no difference in D2BT compared to whites. This
      difference in time to presentation may be one of the factors accounting for poor
      outcomes in this population.

PMID- 27694326
TI  - Percutaneous Pulmonary Valve Implantation Alters Electrophysiologic Substrate.
AB  - BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) is first-line
      therapy for some congenital heart disease patients with right ventricular outflow
      tract dysfunction. The hemodynamics improvements after PPVI are well documented,
      but little is known about its effects on the electrophysiologic substrate. The
      objective of this study is to assess the short- and medium-term
      electrophysiologic substrate changes and elucidate postprocedure arrhythmias.
      METHODS AND RESULTS: A retrospective chart review of patients undergoing PPVI
      from May 2010 to April 2015 was performed. A total of 106 patients underwent
      PPVI; most commonly these patients had tetralogy of Fallot (n=59, 55%) and
      pulmonary insufficiency (n=60, 57%). The median follow-up time was 28 months (7
      63 months). Pre-PPVI, 25 patients (24%) had documented arrhythmias: nonsustained
      ventricular tachycardia (NSVT) (n=9, 8%), frequent premature ventricular
      contractions (PVCs) (n=6, 6%), and atrial fibrillation/flutter (AF/AFL) (n=10,
      9%). Post-PPVI, arrhythmias resolved in 4 patients who had NSVT (44%) and 5
      patients who had PVCs (83%). New arrhythmias were seen in 16 patients (15%): 7
      NSVT, 8 PVCs, and 1 AF/AFL. There was resolution at medium-term follow-up in 6
      (86%) patients with new-onset NSVT and 7 (88%) patients with new-onset PVCs.
      There was no difference in QRS duration pre-PPVI, post-PPVI, and at medium-term
      follow-up (P=0.6). The median corrected QT lengthened immediately post-PPVI but
      shortened significantly at midterm follow-up (P<0.01). CONCLUSIONS: PPVI reduced
      the prevalence of NSVT. The majority of postimplant arrhythmias resolve by 6
      months of follow-up.

PMID- 27694325
TI  - Rapamycin Attenuates Cardiac Fibrosis in Experimental Uremic Cardiomyopathy by
      Reducing Marinobufagenin Levels and Inhibiting Downstream Pro-Fibrotic Signaling.
AB  - BACKGROUND: Experimental uremic cardiomyopathy causes cardiac fibrosis and is
      causally related to the increased circulating levels of the cardiotonic steroid,
      marinobufagenin (MBG), which signals through Na/K-ATPase. Rapamycin is an
      inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR)
      implicated in the progression of many different forms of renal disease. Given
      that Na/K-ATPase signaling is known to stimulate the mTOR system, we speculated
      that the ameliorative effects of rapamycin might influence this pathway. METHODS
      AND RESULTS: Biosynthesis of MBG by cultured human JEG-3 cells is initiated by
      CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 MUmol/L
      of rapamycin inhibited production of MBG in human JEG-2 cells. Male Sprague
      Dawley rats were subjected to either partial nephrectomy (PNx), infusion of MBG,
      and/or infusion of rapamycin through osmotic minipumps. PNx animals showed marked
      increase in plasma MBG levels (1025+/-60 vs 377+/-53 pmol/L; P<0.01), systolic
      blood pressure (169+/-1 vs 111+/-1 mm Hg; P<0.01), and cardiac fibrosis compared
      to controls. Plasma MBG levels were significantly decreased in PNx-rapamycin
      animals compared to PNx (373+/-46 vs 1025+/-60 pmol/L; P<0.01), and cardiac
      fibrosis was substantially attenuated by rapamycin treatment. CONCLUSIONS:
      Rapamycin treatment in combination with MBG infusion significantly attenuated
      cardiac fibrosis. Our results suggest that rapamycin may have a dual effect on
      cardiac fibrosis through (1) mTOR inhibition and (2) inhibiting MBG-mediated
      profibrotic signaling and provide support for beneficial effect of a novel
      therapy for uremic cardiomyopathy.

PMID- 27694329
TI  - Widow wins right to use frozen embryos that were due to be destroyed.

PMID- 27694327
TI  - Nonsustained Atrial Fibrillation in Ischemic Stroke Patients and Stroke-Free
      Controls From the Perspective of Stroke Pathophysiology.
AB  - BACKGROUND: Short-lasting (<30 s), nonsustained episodes of atrial fibrillation
      (NS-AF) are considered a risk factor for future development of paroxysmal or
      persistent AF. Nonetheless, their causal role in stroke pathogenesis is currently
      unknown. In this study we determined the frequency of NS-AF, together with the
      associated clinical and imaging features, in stroke-free controls and ischemic
      stroke patients. METHODS AND RESULTS: A total of 332 controls, >=50 years of age
      and no prior history of stroke or AF, were evaluated with 24-hour Holter
      monitoring for the presence of <30-s-long AF episodes. The demographic and
      cardiovascular features of this cohort, together with imaging finding on magnetic
      resonance imaging, were compared to a consecutive series of >=50-year-old
      ischemic stroke patients without AF (n=498). The prevalence of NS-AF was
      significantly higher among ischemic stroke patients in comparison to controls
      (37% versus 27%; P=0.002). In multivariable analyses, after adjustment for
      demographic and cardiovascular risk factors, patients with ischemic stroke were
      more likely to harbor NS-AF episodes (odds ratio 1.43; 95% CI 1.01-2.02;
      P=0.041). The association between ischemic stroke and NS-AF weakened when the
      analyses were restricted to cryptogenic stroke patients (odds ratio 1.31; 95% CI
      0.82-2.08). No significant association was observed between the presence of
      chronic cortical infarcts and NS-AF. CONCLUSIONS: Our study shows a higher
      prevalence of NS-AF episodes in ischemic stroke patients in comparison to
      controls. Nonetheless, the lack of a stronger association with cryptogenic
      strokes and absence of a relationship with chronic cortical infarcts brings into
      question the causal influence of NS-AF in the ischemic stroke setting.

PMID- 27694330
TI  - Clinton promises to expand healthcare access and cut out-of-pocket costs.

PMID- 27694328
TI  - Novel Role for Matrix Metalloproteinase 9 in Modulation of Cholesterol
      Metabolism.
AB  - BACKGROUND: The development of atherosclerosis is strongly linked to disorders of
      cholesterol metabolism. Matrix metalloproteinases (MMPs) are dysregulated in
      patients and animal models with atherosclerosis. Whether systemic MMP activity
      influences cholesterol metabolism is unknown. METHODS AND RESULTS: We examined
      MMP-9-deficient (Mmp9-/-) mice and found them to have abnormal lipid gene
      transcriptional responses to dietary cholesterol supplementation. As opposed to
      Mmp9+/+ (wild-type) mice, Mmp9-/- mice failed to decrease the hepatic expression
      of sterol regulatory element binding protein 2 pathway genes, which control
      hepatic cholesterol biosynthesis and uptake. Furthermore, Mmp9-/- mice failed to
      increase the expression of genes encoding the rate-limiting enzymes in biliary
      cholesterol excretion (eg, Cyp7a and Cyp27a). In contrast, MMP-9 deficiency did
      not impair intestinal cholesterol absorption, as shown by the 14C-cholesterol and
      3H-sitostanol absorption assay. Similar to our earlier study on Mmp2-/- mice, we
      observed that Mmp9-/- mice had elevated plasma secreted phospholipase A2
      activity. Pharmacological inhibition of systemic circulating secreted
      phospholipase A2 activity (with varespladib) partially normalized the hepatic
      transcriptional responses to dietary cholesterol in Mmp9-/- mice. Functional
      studies with mice deficient in other MMPs suggested an important role for the MMP
      system, as a whole, in modulation of cholesterol metabolism. CONCLUSIONS: Our
      results show that MMP-9 modulates cholesterol metabolism, at least in part,
      through a novel MMP-9-plasma secreted phospholipase A2 axis that affects the
      hepatic transcriptional responses to dietary cholesterol. Furthermore, the data
      suggest that dysregulation of the MMP system can result in metabolic disorder,
      which could lead to atherosclerosis and coronary heart disease.

PMID- 27694331
TI  - A Role for Human N-alpha Acetyltransferase 30 (Naa30) in Maintaining
      Mitochondrial Integrity.
AB  - N-terminal acetylation (Nt-acetylation) by N-terminal acetyltransferases (NATs)
      is one of the most common protein modifications in eukaryotes. The NatC complex
      represents one of three major NATs of which the substrate profile remains largely
      unexplored. Here, we defined the in vivo human NatC Nt-acetylome on a proteome
      wide scale by combining knockdown of its catalytic subunit Naa30 with positional
      proteomics. We identified 46 human NatC substrates, expanding our current
      knowledge on the substrate repertoire of NatC which now includes proteins
      harboring Met-Leu, Met-Ile, Met-Phe, Met-Trp, Met-Val, Met-Met, Met-His and Met
      Lys N termini. Upon Naa30 depletion the expression levels of several organellar
      proteins were found reduced, in particular mitochondrial proteins, some of which
      were found to be NatC substrates. Interestingly, knockdown of Naa30 induced the
      loss of mitochondrial membrane potential and fragmentation of mitochondria. In
      conclusion, NatC Nt-acetylates a large variety of proteins and is essential for
      mitochondrial integrity and function.

PMID- 27694332
TI  - Energetics of acclimation to NaCl by submerged, anoxic rice seedlings.
AB  - BACKGROUND AND AIMS: Our aim was to elucidate how plant tissues under a severe
      energy crisis cope with imposition of high NaCl, which greatly increases ion
      fluxes and hence energy demands. The energy requirements for ion regulation
      during combined salinity and anoxia were assessed to gain insights into ion
      transport processes in the anoxia-tolerant coleoptile of rice. METHODS: We
      studied the combined effects of anoxia plus 50 or 100 mm NaCl on tissue ions and
      growth of submerged rice (Oryza sativa) seedlings. Excised coleoptiles allowed
      measurements in aerated or anoxic conditions of ion net fluxes and O2 consumption
      or ethanol formation and by inference energy production. KEY RESULTS: Over 80 h
      of anoxia, coleoptiles of submerged intact seedlings grew at 100 mm NaCl, but
      excised coleoptiles, with 50 mm exogenous glucose, survived only at 50 mm NaCl,
      possibly due to lower energy production with glucose than for intact coleoptiles
      with sucrose as substrate. Rates of net uptake of Na+ and Cl- by coleoptiles in
      anoxia were about half those in aerated solution. Ethanol formation in anoxia and
      O2 uptake in aerobic solution were each increased by 13-15 % at 50 mm NaCl, i.e.
      ATP formation was stimulated. For acclimation to 50 mm NaCl, the anoxic tissues
      used only 25 % of the energy that was expended by aerobic tissues. Following
      return of coleoptiles to aerated non-saline solution, rates of net K+ uptake
      recovered to those in continuously aerated solution, demonstrating there was
      little injury during anoxia with 50 mm NaCl. CONCLUSION: Rice seedlings survive
      anoxia, without the coleoptile incurring significant injury, even with the
      additional energy demands imposed by NaCl (100 mm when intact, 50 mm when
      excised). Energy savings were achieved in saline anoxia by less coleoptile
      growth, reduced ion fluxes as compared to aerobic coleoptiles and apparent energy
      economic ion transport systems.

PMID- 27694333
TI  - Waardenburg-Shah Syndrome: a rare case in an Indian child.
AB  - A 7-year-old male child presented with a history of discolouration of right eye
      since birth. On examination visual acuity was 6/6 on Snellen's chart in both
      eyes; anterior segment was within normal limits except for the brilliant blue
      discolouration of the inferior quadrant and superior quadrant of right iris and
      left eye iris, respectively. Both eyes had a clear lens and fundus findings were
      within normal limits. A detailed history from parents revealed that the child had
      difficulty in hearing and slurring of speech. In addition, the child had repeated
      episodes of constipation with bilious vomiting during infancy for which a
      diagnosis of fungal sepsis with Hirschsprung's disease was made and the child had
      to undergo a mid-sigmoid loop colostomy for that. A diagnosis of Waardenburg-
      Shah Syndrome was made and the child was referred for hearing and speech
      rehabilitation.

PMID- 27694334
TI  - Fever of unknown origin in a patient initially presenting with traveller's
      diarrhoea.
AB  - A 17-year-old male presented with diarrhoea and malaise following his return from
      Kenya and Tunisia. He was managed as a case of traveller's diarrhoea. Stool
      cultures were negative for pathogenic bacterial growth. Two weeks later he
      presented with worsening lower back pain. MRI of lumbosacral spine suggested L1
      osteomyelitis. CT-guided spinal aspirate grew no organisms and repeat viral
      serology and blood cultures (including tuberculosis screening) were negative. He
      was treated with a 6-week course of ceftriaxone. Back pain did not improve and a
      repeat MRI scan 8 weeks after his antibiotic course indicated progressive changes
      in L1 extending to L2 with an intradiscal abscess. Repeat CT-guided spinal
      aspirate grew Salmonella arizonae sensitive to cotrimoxazole and ceftriaxone. He
      was treated with intravenous ceftriaxone and cotrimoxazole for 12 weeks. A 4
      month follow-up MRI scan showed progressive improvement of the L1/L2 discitis
      with resolution of intradiscal fluid.

PMID- 27694335
TI  - The impact of critically ill children on paediatric ED medication timeliness.
AB  - OBJECTIVES: The presence of critically ill patients may impact care for other ED
      patients. We sought to evaluate whether the presence of a critically ill child
      was associated with the time to (1) receipt of the first medication among other
      patients, and (2) administration of diagnosis-specific medications. METHODS: We
      performed a retrospective cohort study of all paediatric ED visits over 3 years.
      Patients were exposed if they arrived during the first hour of a critically ill
      patient's care. The primary outcome was the time from arrival to first medication
      administration. Secondary outcomes were time to corticosteroids in asthma and
      time to antibiotics for fever/neutropenia. We modelled times to medication using
      median regression, adjusting for demographics, arrival time and weekday, and
      census (number of patients in the ED). RESULTS: We analysed 170 112 visits.
      Median times to first medication for those exposed to 0, 1 and >1 simultaneous
      critically ill patients were 90 min (IQR 54-146), 96 min (IQR 58-157) and 113 min
      (IQR 72-166), respectively (p<0.001). The increase in time to corticosteroids
      among exposed patients versus unexposed was 6 min (IQR 2-14, p=0.11) and in time
      to antibiotic for fever/neutropenia was -4 min (IQR -4 to -11, p=0.13). Modelled
      time to first medication increased 3.1 min (95% CI 0.5 to 5.7) among all exposed
      patients (p=0.02). Time to first medication increased 15.3 min (95% CI 14.7 to
      15.9) for each 10 patient increase in census. CONCLUSIONS: The presence of
      critically ill patients was associated with a delay in medication administration
      to others. Census independently predicted medication delays.

PMID- 27694338
TI  - The healthcare quality improvement partnership national early arthritis audit.

PMID- 27694339
TI  - Journal of Cell Science is going green.

PMID- 27694336
TI  - Patient- and clinician-reported outcomes for patients with new presentation of
      inflammatory arthritis: observations from the National Clinical Audit for
      Rheumatoid and Early Inflammatory Arthritis.
AB  - OBJECTIVES: Our aim was to conduct a national audit assessing the impact and
      experience of early management of inflammatory arthritis by English and Welsh
      rheumatology units. The audit enables rheumatology services to measure for the
      first time their performance, patient outcomes and experience, benchmarked to
      regional and national comparators. METHODS: All individuals >16 years of age
      presenting to English and Welsh rheumatology services with suspected new-onset
      inflammatory arthritis were included in the audit. Clinician- and patient-derived
      outcome and patient-reported experience measures were collected. RESULTS: Data
      are presented for the 6354 patients recruited from 1 February 2014 to 31 January
      2015. Ninety-seven per cent of English and Welsh trusts participated. At the
      first specialist assessment, the 28-joint DAS (DAS28) was calculated for 2659
      (91%) RA patients [mean DAS28 was 5.0 and mean Rheumatoid Arthritis Impact of
      Disease (RAID) score was 5.6]. After 3 months of specialist care, the mean DAS28
      was 3.5 and slightly >60% achieved a meaningful DAS28 reduction. The average RAID
      score and reduction in RAID score were 3.6 and 2.4, respectively. Of the working
      patients ages 16-65 years providing data, 7, 5, 16 and 37% reported that they
      were unable to work, needed frequent time off work, occasionally and rarely
      needed time off work due to their arthritis, respectively; only 42% reported
      being asked about their work. Seventy-eight per cent of RA patients providing
      data agreed with the statement 'Overall in the last 3 months I have had a good
      experience of care for my arthritis'; <2% disagreed. CONCLUSION: This audit
      demonstrates that most RA patients have severe disease at the time of
      presentation to rheumatology services and that a significant number continue to
      have high disease activity after 3 months of specialist care. There is a clear
      need for the National Health Service to develop better systems for capturing,
      coding and integrating information from outpatient clinics, including measures of
      patient experience and outcome and measures of ability to work.

PMID- 27694337
TI  - Achievement of NICE quality standards for patients with new presentation of
      inflammatory arthritis: observations from the National Clinical Audit for
      Rheumatoid and Early Inflammatory Arthritis.
AB  - OBJECTIVES: A national audit was performed assessing the early management of
      suspected inflammatory arthritis by English and Welsh rheumatology units. The aim
      of this audit was to measure the performance of rheumatology services against
      National Institute for Health and Care Excellence (NICE) quality standards (QSs)
      for the management of early inflammatory arthritis benchmarked to regional and
      national comparators for the first time in the UK. METHODS: All individuals >16
      years of age presenting to rheumatology services in England and Wales with
      suspected new-onset inflammatory arthritis were included in the audit.
      Information was collected against six NICE QSs that pertain to early inflammatory
      arthritis management. RESULTS: We present national data for the 6354 patients
      recruited from 1 February 2014 to 31 January 2015; 97% of trusts and health
      boards in England and Wales participated in this audit. Only 17% of patients were
      referred by their general practitioner within 3 days of first presentation.
      Specialist rheumatology assessment occurred within 3 weeks of referral in 38% of
      patients. The target of DMARD initiation within 6 weeks of referral was achieved
      in 53% of RA patients; 36% were treated with combination DMARDs and 82% with
      steroids within the first 3 months of specialist care. Fifty-nine per cent of
      patients received structured education on their arthritis within 1 month of
      diagnosis. In total, 91% of patients had a treatment target set; the agreed
      target was achieved within 3 months of specialist review in only 27% of patients.
      Access to urgent advice via a telephone helpline was reported to be available in
      96% of trusts. CONCLUSION: The audit has highlighted gaps between NICE standards
      and delivery of care, as well as substantial geographic variability.

PMID- 27694340
TI  - Talin2-mediated traction force drives matrix degradation and cell invasion.
AB  - Talin binds to beta-integrin tails to activate integrins, regulating cell
      migration, invasion and metastasis. There are two talin genes, TLN1 and TLN2,
      encoding talin1 and talin2, respectively. Talin1 regulates focal adhesion
      dynamics, cell migration and invasion, whereas the biological function of talin2
      is not clear and, indeed, talin2 has been presumed to function redundantly with
      talin1. Here, we show that talin2 has a much stronger binding to beta-integrin
      tails than talin1. Replacement of talin2 Ser339 with Cys significantly decreased
      its binding to beta1-integrin tails to a level comparable to that of talin1.
      Talin2 localizes at invadopodia and is indispensable for the generation of
      traction force and invadopodium-mediated matrix degradation. Ablation of talin2
      suppressed traction force generation and invadopodia formation, which were
      restored by re-expressing talin2 but not talin1. Furthermore, re-expression of
      wild-type talin2 (but not talin2S339C) in talin2-depleted cells rescued
      development of traction force and invadopodia. These results suggest that a
      strong interaction of talin2 with integrins is required to generate traction,
      which in turn drives invadopodium-mediated matrix degradation, which is key to
      cancer cell invasion.

PMID- 27694341
TI  - Development of an Interception Glove Sampler for Skin Exposures to Aromatic
      Isocyanates.
AB  - OBJECTIVES: Skin is an important exposure route for isocyanate chemicals and
      contributes to systemic sensitization. Methods for assessing skin exposure are
      currently limited and generally rely upon removal (e.g. tape-strip) techniques
      prone to underestimation. The aim of this study is to (i) develop and field test
      an interception-based hand exposure sampler to monitor potential skin exposure to
      isocyanates in the workplace, (ii) to develop an analytical method based on ultra
      high-performance liquid chromatography-UV absorbance-tandem mass spectrometry
      (UHPLC-UV-MS/MS) for analyzing glove samples; and (iii) compare it with tape
      stripping skin sampling method. METHODS: Laboratory investigations assessed
      different glove materials/fabrics, methods for impregnating with 1-(9
      anthracenylmethyl)piperazine (MAP) derivatizing agent, methylene diphenyl
      diisocyanate (MDI) uptake and recovery, and durability. Following use, gloves
      were dissected into sections corresponding to different spatial regions (finger,
      palm) and analyzed using a newly developed UHPLC-UV-MS/MS method capable of
      differentiating and quantitating different MDI isomers with high sensitivity.
      Performance of the glove sampler was further assessed in a pilot field study
      using six workers. RESULTS: A MAP-impregnated thin cotton glove sampler and UHPLC
      UV-MS/MS analytical method for detecting MDI were successfully developed in
      laboratory studies. In subsequent field studies, a total of 384 samples from 14
      glove pairs identified full-shift exposures ranged from 0.01 to 306 ug of 4,4'
      MDI/worker for each hand. Surface area adjusted MDI values measured with the
      glove sampler (0.13-572ng MDI cm-2) were considerably higher (~400-fold) than
      values obtained with tape stripping. CONCLUSION: A glove sampler and a novel
      UHPLC-UV-MS/MS analytical method were developed to quantitatively measure MDI
      skin exposure. The novel interception technique overcomes inherent limitations of
      removal techniques for measuring isocyanate skin exposure and may be useful in
      exposure surveillance and future research on isocyanate's health risks.

PMID- 27694343
TI  - Cross-Sectional and Prospective Associations Between beta-Amyloid in the Brain
      and Chair Rise Performance in Nondementia Older Adults With Spontaneous Memory
      Complaints.
AB  - BACKGROUND: The objectives of this study were to examine the cross-sectional and
      prospective associations of muscle functional performance as assessed by a chair
      rise test and brain amyloid load among nondemented older adults with spontaneous
      memory complaints. METHODS: This is a secondary analysis, with an observational
      design, using data from the MAPT randomized controlled trial. Individuals
      assessed for brain amyloid load (florbetapir F18 positron emission tomography)
      and without clinical dementia (N = 269 aged 75.2+/-4.2 years; 60.2% women)
      participated in the study. Cortical and regional standard uptake value ratios
      (SUVRs) were obtained. The main outcome measure was the 5-repetition chair rise
      performance (maximum speed-higher is better), which was assessed at baseline and
      at 6, 12, 24, and 36 months. Adjusted multiple linear (cross-sectional) and mixed
      effect (overtime) regressions were performed. RESULTS: Any of mean cortical
      (regions of interest) and each regional SUVRs (anterior cingulate, anterior
      putamen, caudate, hippocampus, medial orbitofrontal cortex, occipital cortex,
      parietal cortex, pons, posterior cingulate, posterior putamen, precuneus,
      semioval center, and temporal cortex) were not associated to chair rise after
      adjustment for multiplicity. These findings were obtained for both cross
      sectional and prospective associations. CONCLUSIONS: Brain amyloid was not found
      to be associated to chair rise performance in nondemented older adults with
      memory complaints. Potential mechanisms on the links, if any, of amyloid load
      with physical performance are probably not dependent on muscle function.

PMID- 27694342
TI  - A Tomato Vacuolar Invertase Inhibitor Mediates Sucrose Metabolism and Influences
      Fruit Ripening.
AB  - Fruit ripening is a complex process that involves a series of physiological and
      biochemical changes that ultimately influence fruit quality traits, such as color
      and flavor. Sugar metabolism is an important factor in ripening, and there is
      evidence that it influences various aspects of ripening, although the associated
      mechanism is not well understood. In this study, we identified and analyzed the
      expression of 36 genes involved in Suc metabolism in ripening tomato (Solanum
      lycopersicum) fruit. Chromatin immunoprecipitation and gel mobility shift assays
      indicated that SlVIF, which encodes a vacuolar invertase inhibitor, and SlVI,
      encoding a vacuolar invertase, are directly regulated by the global fruit
      ripening regulator RIPENING INHIBITOR (RIN). Moreover, we showed that SlVIF
      physically interacts with SlVI to control Suc metabolism. Repression of SlVIF by
      RNA interference delayed tomato fruit ripening, while overexpression of SlVIF
      accelerated ripening, with concomitant changes in lycopene production and
      ethylene biosynthesis. An isobaric tags for relative and absolute quantification
      based quantitative proteomic analysis further indicated that the abundance of a
      set of proteins involved in fruit ripening was altered by suppressing SlVIF
      expression, including proteins associated with lycopene generation and ethylene
      synthesis. These findings provide evidence for the role of Suc in promoting fruit
      ripening and establish that SlVIF contributes to fruit quality and the RIN
      mediated ripening regulatory mechanisms, which are of significant agricultural
      value.

PMID- 27694344
TI  - Longevity-Associated FOXO3 Genotype and its Impact on Coronary Artery Disease
      Mortality in Japanese, Whites, and Blacks: A Prospective Study of Three American
      Populations.
AB  - Background: We recently reported that protection against coronary artery disease
      (CAD) mortality is the major contributor to longer life associated with FOXO3
      genotype. The present study examined this relation in more detail. Methods: We
      performed a 15-year observational study of 3,584 older American men of Japanese
      ancestry from the Kuakini Honolulu Heart Program cohort and 1,595 White and 1,067
      Black elderly individuals from the Health Aging and Body Composition study.
      Results: Multivariate Cox regression models demonstrated that carriage of the
      longevity-associated G allele of FOXO3 single nucleotide polymorphisms rs2802292
      was a protective factor against CAD mortality in all three populations. In
      Japanese and Whites, but not in Blacks, the protective effect of the G allele was
      little changed in models adjusted for other major risk factors. Population
      attributable risk (PAR) models found that the nonprotective TT genotype
      contributed 15%, 9%, and 3% to CAD mortality risk in Japanese, White, and Black
      Americans, respectively, and was one of the top three contributing factors to CAD
      mortality. In Japanese, this effect size was comparable with hypertension (15%),
      but in Whites and Blacks PAR for hypertension was higher (29% and 26%,
      respectively). G-allele carriers had lower plasma TNF-alpha than noncarriers,
      suggesting inflammation as a potential mediating factor for CAD mortality risk.
      Conclusion: FOXO3 genotype is an important risk factor for CAD mortality in older
      populations. More research is needed to identify potential mechanisms and targets
      for intervention.

PMID- 27694345
TI  - Impact of Feeding on Contaminated Prey on the Life Parameters of Nesidiocoris
      Tenuis (Hemiptera: Miridae) Adults.
AB  - Insecticide selectivity to natural enemies is an important concern in integrated
      pest management programs. Although there is a wide range of information
      concerning pesticide lethal and sublethal effects on contaminated surfaces,
      little is known when the route of exposure occurs at a trophic level. This study
      evaluates this route of pesticide intake on the omnivorous predator Nesidiocoris
      tenuis (Reuter) (Hemiptera: Miridae) for the first time. Under laboratory
      conditions, prey treated with six insecticides (flubendiamide, spirotetramat,
      deltamethrin, flonicamid, metaflumizone, and sulfoxaflor) were offered to N.
      tenuis adults for 3 days. Mortality (24, 48, and 72 h after treatment), offspring
      production (third until eighth day) and longevity were documented. Metaflumizone
      and sulfoxaflor were classified as moderately harmful products because although
      the percentage of mortality was only 28 and 36%, respectively, both products
      caused a severe decrease in offspring production and longevity. Flonicamid and
      flubendiamide were classified as slightly harmful products; although they did not
      have a lethal effect, sublethal impact was important on the parameters studied.
      Spirotetramat and deltamethrin were insecticides categorized as harmless. This
      information could be useful for selecting the most appropriate insecticides to
      control pests in tomato crops in which N. tenuis is a relevant biological control
      agent.

PMID- 27694347
TI  - Final transitions to place of death: patients and families wishes.
AB  - Purpose: This four-country study (Belgium, the Netherlands, Italy and Spain)
      examines prevalence and types of final transitions between care settings of
      cancer patients and the extent to which patient/family wishes are cited as a
      reason for the transition. Methods: Data were collected from the EUROSENTI-MELC
      study over a 2-year period. General practitioners within existing Sentinel
      Networks registered weekly all deaths of patients within practices using a
      standardized questionnaire. This registration included place of care in the final
      3 months and wishes for the final transition to place of death. All non-sudden
      deaths due to cancer (+18 years) were included in the analyses. Results: We
      included 2048 non-sudden cancer deaths; 63% of patients had at least one
      transition between care settings in the final 3 months of life. 'Hospital death
      from home' (25-55%) and 'home death from hospital' (16-30%) were the most
      frequent types of final transitions in all countries. Patients' or families'
      wishes were mentioned as a reason for a final transition in 5-27% (P < 0.001) and
      10-22% (P = 0.002) across countries. Conclusions: 'Hospital deaths from home' is
      the most prevalent final transition in three of four countries studied, in a
      significant minority of cases because of patient/family wishes.

PMID- 27694346
TI  - Insect Visitors and Potential Pollinators of Orchis militaris (Orchidaceae) in
      Southern Belgium.
AB  - As part of a research project on the food deception strategy in Orchis militaris
      (L.), the objective of this study was to identify insect visitors and potential
      pollinators of this orchid species in Belgium. In 2013, insects were collected
      over 2 d per site in five localities distributed in Southern Belgium (Wallonia).
      A total of 104 insects belonging to 49 species were caught. Dipterans were the
      most abundant visitors (50% of total specimens), followed by Hymenopterans (32%).
      Rhingia campestris Meigen, Bombylius venosus Mikan, Apis mellifera (L.), and
      Bombus lapidarius (L.) were the most abundant species. Only five specimens bore
      one to more than 10 pollinia: four honeybees (A. mellifera) and one bumblebee
      worker (B. lapidarius). These two species should be considered as potential
      pollinators in the study area, but probably not confirmed ones.

PMID- 27694348
TI  - Implementing extreme weather event advice and guidance in English public health
      systems.
AB  - Background: Extreme weather events (EWEs) can significantly impact on mortality
      and morbidity in the UK. How EWE guidance is disseminated and applied across
      health and social care systems, at the local, operational level, is not well
      understood. Methods: This exploratory study develops tools and resources to
      assist local stakeholders to cascade national 'all weather' EWE guidance across
      local systems. These resources are also used to evaluate the local interpretation
      and implementation of this advice and guidance within three local authority
      areas. In total, five discussion group meetings were held and 45 practitioners
      took part in the study. A thematic analysis was conducted. Results: The main
      themes emerging from the analysis related to awareness of PHE guidance for EWE
      preparedness, data sharing feasibility, community engagement, specific conditions
      in remote rural areas and capacity of frontline staff. Conclusions: The relative
      difficulty in finding where the study 'best fits' on local stakeholders' agendas
      suggests that year-round and preparedness planning for EWEs may not have been
      considered a high priority in participating areas. This study adds to the
      relatively limited evidence internationally concerning the practical
      implementation at local level of national adaptation advice and guidance and
      potential barriers to achieving this.

PMID- 27694349
TI  - Using mobile technology to optimize disease surveillance and healthcare delivery
      at mass gatherings: a case study from India's Kumbh Mela.
AB  - Background: Planning for mass gatherings often includes temporary healthcare
      systems to address the needs of attendees. However, paper-based record keeping
      has traditionally precluded the timely application of collected clinical data for
      epidemic surveillance or optimization of healthcare delivery. We evaluated the
      feasibility of harnessing ubiquitous mobile technologies for conducting disease
      surveillance and monitoring resource utilization at the Allahabad Kumbh Mela in
      India, a 55-day festival attended by over 70 million people. Methods: We
      developed an inexpensive, tablet-based customized disease surveillance system
      with real-time analytic capabilities, and piloted it at five field hospitals.
      Results: The system captured 49 131 outpatient encounters over the 3-week study
      period. The most common presenting complaints were musculoskeletal pain (19%),
      fever (17%), cough (17%), coryza (16%) and diarrhoea (5%). The majority of
      patients received at least one prescription. The most common prescriptions were
      for antimicrobials, acetaminophen and non-steroidal anti-inflammatory drugs.
      There was great inter-site variability in caseload with the busiest hospital
      seeing 650% more patients than the least busy hospital, despite identical
      staffing. Conclusions: Mobile-based health information solutions developed with a
      focus on user-centred design can be successfully deployed at mass gatherings in
      resource-scarce settings to optimize care delivery by providing real-time access
      to field data.

PMID- 27694350
TI  - Optimization of cell lines as tumour models by integrating multi-omics data.
AB  - Cell lines are widely used as in vitro models of tumorigenesis. However, an
      increasing number of researchers have found that cell lines differ from their
      sourced tumour samples after long-term cell culture. The application of
      unsuitable cell lines in experiments will affect the experimental accuracy and
      the treatment of patients. Therefore, it is imperative to identify optimal cell
      lines for each cancer type. Here, we review the methods used to evaluate cell
      lines since 2005. Furthermore, gene expression, copy number and mutation profiles
      from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia are used to
      calculate similarity between tumours and cell lines. Then, the ideal cell lines
      to use for experiments for eight types of cancers are found by combining the
      results with Gene Ontology functional similarity. After verification, the optimal
      cell lines have the same genomic characteristics as their homologous tumour
      samples. The contaminated cell lines identified in previous research are also
      determined to be unsuitable in vitro cancer models here. Moreover, our study
      suggests that some of the commonly used cell lines are not suitable cancer
      models. In summary, we provide a reference for ideal cell lines to use in in
      vitro experiments and contribute to improving the accuracy of future cancer
      research. Furthermore, this research provides a foundation for identifying more
      effective treatment strategies.

PMID- 27694353
TI  - The Toxic Wake of Rudeness: Why It Matters.

PMID- 27694354
TI  - The ABCDs of Managing Morbidly Obese Patients in Intensive Care Units.
AB  - More than one-third of the US adult population and 17% of the youth are now
      obese, and obesity is associated with more than $147 billion a year in health
      care costs. Critical care nurses should understand the physiological differences
      and practice guidelines for patients with a body mass index greater than 30. The
      ABCD approach encompasses key clinical concepts in the management of critically
      ill obese and morbidly obese patients, including management of airways and
      breathing, minimizing nurses' back and other injuries, increasing awareness of
      bias, circulation problems, risks of decubitus ulcers and other skin breakdown,
      differences in drug calculations and metabolism, limitations in diagnostic
      equipment and imaging, diet and nutritional recommendations, and concerns with
      durable medical equipment.

PMID- 27694355
TI  - Esophageal Pressure Measurements in Patients With Acute Respiratory Distress
      Syndrome.
AB  - Esophageal balloons are used in the respiratory monitoring of critical care
      patients. After the esophageal pressure is measured, the corresponding pleural
      pressure in the thorax can be projected, enabling lung-thorax compliance to be
      partitioned into chest-wall compliance and lung compliance. The esophageal
      balloon allows determination of transpulmonary pressures and a correspondingly
      individually tailored approach to respiratory care, such as patient-specific
      titration of positive end-expiratory pressure for patients with extrapulmonary
      acute respiratory distress syndrome. Esophageal balloon monitoring provides
      critical information for selecting ventilation strategies to use in patients with
      acute respiratory distress syndrome.

PMID- 27694351
TI  - A systematic evaluation of normalization methods in quantitative label-free
      proteomics.
AB  - To date, mass spectrometry (MS) data remain inherently biased as a result of
      reasons ranging from sample handling to differences caused by the
      instrumentation. Normalization is the process that aims to account for the bias
      and make samples more comparable. The selection of a proper normalization method
      is a pivotal task for the reliability of the downstream analysis and results.
      Many normalization methods commonly used in proteomics have been adapted from the
      DNA microarray techniques. Previous studies comparing normalization methods in
      proteomics have focused mainly on intragroup variation. In this study, several
      popular and widely used normalization methods representing different strategies
      in normalization are evaluated using three spike-in and one experimental mouse
      label-free proteomic data sets. The normalization methods are evaluated in terms
      of their ability to reduce variation between technical replicates, their effect
      on differential expression analysis and their effect on the estimation of
      logarithmic fold changes. Additionally, we examined whether normalizing the whole
      data globally or in segments for the differential expression analysis has an
      effect on the performance of the normalization methods. We found that variance
      stabilization normalization (Vsn) reduced variation the most between technical
      replicates in all examined data sets. Vsn also performed consistently well in the
      differential expression analysis. Linear regression normalization and local
      regression normalization performed also systematically well. Finally, we discuss
      the choice of a normalization method and some qualities of a suitable
      normalization method in the light of the results of our evaluation.

PMID- 27694356
TI  - Cardiovascular Disease and HIV: Pathophysiology, Treatment Considerations, and
      Nursing Implications.
AB  - HIV infection has progressed from an acute, terminal disease to a chronic illness
      with cardiovascular disease as the leading cause of death among persons living
      with HIV. As persons living with HIV infection continue to become older,
      traditional risk factors for atherosclerosis compounded by the pathophysiological
      effects of HIV infection and antiretroviral therapy markedly increase the risk
      for cardiovascular disease. Further, persons living with HIV are also at high
      risk for cardiomyopathy. Critical care nurses must recognize the risk factors for
      cardiovascular disease and the pathophysiology and complex treatment options in
      order to manage care of these patients and facilitate multidisciplinary
      collaboration. Two case studies are used to highlight the treatment options and
      nursing considerations associated with cardiovascular disease among persons
      living with HIV.

PMID- 27694357
TI  - Understanding the Hybrid Stage I Approach for Hypoplastic Left Heart Syndrome.
AB  - Hybrid stage I palliation combines cardiothoracic surgery and interventional
      transcatheter procedures for treatment of hypoplastic left heart syndrome. The
      approach is an alternative to the Norwood procedure, the traditional first stage
      of surgical palliation. Hybrid stage I palliation involves placing bilateral
      branch pulmonary artery bands and a patent ductus arteriosus stent through a
      median sternotomy, performed without cardiopulmonary bypass. The purpose of the
      bands is to control blood flow to the lungs and protect the pulmonary bed while
      the stent sustains systemic cardiac output. A balloon atrial septostomy is
      performed to create an atrial septal defect for unobstructed blood flow from the
      left atrium to the right atrium. The second stage of palliative surgery is the
      comprehensive stage II, which incorporates removal of the stent and pulmonary
      artery bands, atrial septectomy, anastomosis of the diminutive ascending aorta to
      the main pulmonary artery, aortic arch augmentation, and bidirectional
      cavopulmonary anastomosis. The traditional Fontan procedure completes the series
      of palliation.

PMID- 27694359
TI  - Good Witch or Bad Witch?

PMID- 27694358
TI  - Clarification and Mitigation of Ethical Problems Surrounding Withdrawal of
      Extracorporeal Membrane Oxygenation.
AB  - Extracorporeal membrane oxygenation (ECMO) is temporary life-support technology
      that provides time to rest the cardiac and respiratory system of critically ill
      people with acute, reversible medical conditions. Health care providers face
      emotional and challenging situations, where death may result, when withdrawing
      ECMO. A deepening of understanding of the ethical issues involved can aid
      clinicians in handling such difficult situations, leading to a possible
      mitigation of the moral problems. Toward this end, the ethical issues raised in
      the consideration of ECMO withdrawal are analyzed with respect to the ethical
      principles and concepts of autonomy, nonmaleficence/beneficence, medical
      futility, moral distress, and justice. In particular, these issues are considered
      in relation to how they affect and can be addressed by staff nurses and advanced
      practice nurses in the intensive care unit. Advanced practice nurses in
      particular can represent the voice of nurses to promote a healthier workplace in
      situations of moral distress related to stopping ECMO life-support technology and
      in developing clear and consistent guidelines for ceasing ECMO treatment, all
      leading toward clarification and mitigation of the ethical problems surrounding
      the withdrawal of this critical technology.

PMID- 27694360
TI  - Scope of Practice.

PMID- 27694361
TI  - Easy as ABC: How Staff Nurses Transformed Unit Culture to Assess and Manage
      Delirium in the Intensive Care Unit.

PMID- 27694362
TI  - I Am a Critical Care Nurse.

PMID- 27694363
TI  - Use of Ventilator Bundle and Staff Education to Decrease Ventilator-Associated
      Pneumonia in Intensive Care Patients.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP), one of the most common
      hospital-acquired infections, has a high mortality rate. OBJECTIVES: To evaluate
      the incidence of VAP in a multidisciplinary intensive care unit and to examine
      the effects of the implementation of ventilator bundles and staff education on
      its incidence. METHODS: A 24-month-long before/after study was conducted, divided
      into baseline, intervention, and postintervention periods. VAP incidence and
      rate, the microbiological profile, duration of mechanical ventilation, and length
      of stay in the intensive care unit were recorded and compared between the
      periods. RESULTS: Of 1097 patients evaluated, 362 met the inclusion criteria. The
      baseline VAP rate was 21.6 per 1000 ventilator days. During the postintervention
      period, it decreased to 11.6 per 1000 ventilator days (P = .01). Length of stay
      in the intensive care unit decreased from 36 to 27 days (P = .04), and duration
      of mechanical ventilation decreased from 26 to 21 days (P = .06). CONCLUSIONS:
      VAP incidence was high in a general intensive care unit in a Greek hospital.
      However, implementation of a ventilator bundle and staff education has decreased
      both VAP incidence and length of stay in the unit.

PMID- 27694365
TI  - Assessment and Management of Delirium Across the Life Span.

PMID- 27694366
TI  - Preventing Venous Thromboembolism in Adults.

PMID- 27694364
TI  - Educating Health Care Providers in Treatment of Patients With Ebola Virus
      Disease.
AB  - Nurses manage patients with common infectious diseases by following institutional
      guidelines based on expert advice, evidence in the literature, and a wealth of
      experience. Today nurses are challenged to provide care to patients with
      multidrug-resistant organisms and virulent infectious diseases such as Ebola
      virus disease. Management of some patients with virulent infectious diseases
      occurs in the context of minimal experience with the pathogen, course of
      infection, diagnostics, nursing care, and treatment. Limited evidence exists in
      the US or international literature about direct nursing care of patients with
      virulent infectious diseases in the community, clinic, or hospital. Workplaces
      may have insufficient supplies, equipment, and knowledge of the management of
      patients with these diseases. At the National Institutes of Health Clinical
      Center in Bethesda, Maryland, nursing education strategies for enhanced
      experiential learning are used to prepare staff to care for patients with
      virulent infectious diseases, especially Ebola virus disease.

PMID- 27694367
TI  - Single and mixed feline lungworm infections: clinical, radiographic and
      therapeutic features of 26 cases (2013-2015).
AB  - Objectives The aim of this study was to retrospectively describe clinical,
      radiographic and therapeutic features of feline lungworm infection. Methods
      Medical records of cats with lungworm diagnosis, thoracic radiography and without
      concurrent diseases between 2013 and 2015 were reviewed. Collection of data
      included physical examination, haematology, serum biochemistry, therapy with a
      variety of anthelmintics and outcomes. Results Thirty-seven records were
      recovered and 26 were included in the study. Single infections by
      Aelurostrongylus abstrusus (n = 15), Troglostrongylus brevior (n = 3) and
      Capillaria aerophila (n = 1) and coinfections by T brevior/ A abstrusus (n = 6)
      and T brevior/ C aerophila (n = 1) were diagnosed. The most common respiratory
      signs were coughing (n = 12), increased vesicular sounds (n = 10), dyspnoea (n =
      9), such as laboured breathing, orthopnoea or open-mouth breathing, and
      tachypnoea (n = 6). Two cats were subclinically infected. The most common
      laboratory abnormality was anaemia (n = 7). Radiographic patterns recorded were
      interstitial (n = 24), bronchial (n = 21), alveolar (n = 10) and vascular (n =
      2). Twenty-five cats had a complete recovery within 2-6 weeks of therapy. One
      kitten died 7 days after the diagnosis. Conclusions and relevance Lungworms
      should always be included in the differential diagnosis in cats living in endemic
      areas and presenting with respiratory signs and radiographic abnormalities. A
      copromicroscopic examination should be considered as the first diagnostic step
      for all cats at risk of lungworm infections. In most cases, timely therapy with a
      variety of anthelmintics guarantees recovery.

PMID- 27694368
TI  - Placement of subcutaneous ureteral bypasses without fluoroscopic guidance in cats
      with ureteral obstruction: 19 cases (2014-2016).
AB  - Objectives The purpose of this study was to describe the perioperative and
      postoperative complications as well as short-term and long-term outcomes in cats
      with ureteral obstructions treated by placement of a subcutaneous ureteral bypass
      (SUB) device without imaging control. The second objective of this study was to
      compare cats treated by SUB device with cats treated by traditional surgical
      intervention. Methods Data were obtained retrospectively from the medical records
      (2014-2016) of cats that underwent SUB placement (SUB cats) and cats that
      underwent traditional ureteral surgery (C cats). Results Nineteen SUB devices
      were placed without fluoroscopic, radiographic or ultrasonographic guidance in 13
      cats. Fifteen traditional interventions (ureterotomy and neoureterocystostomy)
      were performed in 11 cats. Successful placement of the SUB device was achieved in
      all cats with only one major intraoperative complication (kinking of the kidney
      catheter) and one minor intraoperative complication (misplacement of the kidney
      catheter). Eleven SUB cats recovered from the surgical procedure; two SUB cats
      and three C cats died during the anaesthesia recovery period. Postoperative SUB
      complications included anaemia (n = 2), urinary tract infection (UTI) (n = 4),
      non-infectious cystitis (n = 5) and SUB device obstruction (n = 1). Postoperative
      traditional surgery complications included anaemia (n = 7), UTIs (n = 6), non
      infectious cystitis (n = 1), re-obstruction (n = 4) and ureteral stricture (n =
      1). Median postoperative duration of hospitalisation (3 days) was significantly
      shorter for SUB cats than for C cats ( P = 0.013). Ten SUB cats (76.9%) and four
      C cats (40%) were still alive at a median follow-up of 225 days and 260 days,
      respectively. Owners were completely (90%) or mostly (10%) satisfied with the SUB
      device placement. Conclusions and relevance SUB device placement appears to be an
      effective and safe option for treating ureteral obstruction in cats, and this
      study has shown that fluoroscopic guidance is not essential in all cases.

PMID- 27694369
TI  - Increased detection of Dirofilaria immitis antigen in cats after heat
      pretreatment of samples.
AB  - Objectives To determine whether pretreating diagnostic samples with heat
      increases the detection of Dirofilaria immitis antigen in adult cats, we
      evaluated feline serum and plasma samples collected in heartworm-endemic areas of
      the southern United States. Methods Commercial microtiter well assays for
      detection of D immitis antigen were used to evaluate serum or plasma samples from
      385 shelter and free-roaming cats from the southcentral and southeastern United
      States before and after heat treatment; commercial antibody tests were performed
      on a subset of samples. Results Prior to sample heat treatment, 1/220 (0.5%)
      shelter cats and 4/165 (2.4%) free-roaming cats had detectable D immitis antigen.
      After heat pretreatment, the detection rate increased to 13/220 (5.9%) and 13/165
      (7.9%), respectively. Antibody reactive to D immitis was significantly more
      common ( P <0.001) in the serum of cats that were antigen positive after heat
      treatment (10/13; 76.9%) than serum from cats that remained antigen negative
      after heat treatment (22/163; 13.5%). Conclusions and relevance Heat pretreatment
      of feline samples increased antigen detection by commercial assays for D immitis
      and improved overall concordance of antigen and antibody test results in antigen
      positive samples in this population. Although further work to investigate the
      specificity of D immitis antigen assays when using pre-treated samples is
      warranted, this approach may be useful in the diagnosis of heartworm infection in
      individual cats and may increase the accuracy of surveys based on antigen
      detection.

PMID- 27694370
TI  - Cohort Differences in Cognitive Aging in the Longitudinal Aging Study Amsterdam.
AB  - Objectives: This study aims to examine cohort differences in cognitive
      performance and rates of change in episodic memory, processing speed, inductive
      reasoning, and general cognitive performance and to investigate whether these
      cohort effects may be accounted for by education attainment. Method: The first
      cohort (N = 705) was born between 1920 and 1930, whereas the second cohort (N =
      646) was born between 1931 and 1941. Both birth cohorts were aged 65 to 75 years
      at baseline and were followed up 3 and 6 years later. Data were analyzed using
      linear mixed models. Results: The later born cohort had better general cognitive
      performance, inductive reasoning, and processing speed at baseline, but cohort
      differences in inductive reasoning and general cognitive performance disappeared
      after adjusting for education. The later born cohort showed steeper decline in
      processing speed. Memory decline was steeper in the earlier born cohort but only
      from Time 1 to Time 3 when the same memory test was administered. Education did
      not account for cohort differences in cognitive decline. Discussion: The later
      born cohort showed better initial performance in certain cognitive abilities, but
      no better preservation of cognitive abilities overtime compared with the earlier
      born cohort. These findings carry implications for healthy cognitive aging.

PMID- 27694371
TI  - From Classroom to Capitol: Building Advocacy Capacity Through State-Level
      Advocacy Experiences.
AB  - This commentary provides insight from Community Health Education and Master of
      Public Health students on the benefits of participating in a state-level Advocacy
      Experience and provides a theoretical framework for increased advocacy intention
      among students as a result of participating in a state-level Advocacy Experience.
      Providing students the opportunity to translate what they learn about advocacy in
      the classroom into advocacy in action with policy makers is vital to the career
      development of our future health education professionals and is key to increasing
      advocacy capacity within our profession. This article builds on previous work
      from emerging public health professionals highlighting the role of policy
      advocacy in professional development and provides additional perspectives from
      the next generation of health education specialists.

PMID- 27694372
TI  - The EDIC Method: An Engaging and Comprehensive Approach for Creating Health
      Department Workforce Development Plans.
AB  - In 2013, the Nebraska Department of Health & Human Services, Division of Public
      Health (Nebraska's State Health Department); and the University of Nebraska
      Medical Center, College of Public Health developed a comprehensive approach to
      assess workforce training needs. This article outlines the method used to assess
      the education and training needs of Division staff, and develop comprehensive
      workforce development plans to address those needs. The EDIC method (Engage,
      Develop, Identify, and Create) includes the following four phases: (1) Engage
      Stakeholders, (2) Develop Assessment, (3) Identify Training Needs, and (4) Create
      Development Plans. The EDIC method provided a process grounded in science and
      practice, allowed input, and produced buy-in from staff at all levels throughout
      the Division of Public Health. This type of process provides greater assurance
      that the most important gaps in skills and competencies will be identified.
      Although it is a comprehensive approach, it can be replicated at the state or
      local level across the country.

PMID- 27694373
TI  - Micro and nanoparticles as possible pathogenetic co-factors in mixed
      cryoglobulinemia.
AB  - BACKGROUND: Mixed cryoglobulinemia (MC) is a rare multisystem disease whose
      aetiopathogenesis is not completely understood. Hepatitis C virus (HCV) infection
      may have a causative role, and genetic and/or environmental factors may also
      contribute. AIMS: To investigate the presence and possible role of environmental
      agents in MC. METHODS: We recruited 30 HCV-infected MC patients with different
      clinical manifestations and a control group of 30 healthy, sex-/age-matched
      volunteers. We collected serum samples from each patient and incubated at 4
      degrees C for 7 days to obtain cryoprecipitate samples. We used environmental
      scanning electron microscopy (ESEM) and energy dispersive X-ray spectroscopy
      microanalysis to verify the presence of microparticles (MPs) and nanoparticles
      (NPs) in serum and cryoprecipitate samples. We evaluated environmental exposure
      using a medical and occupational history questionnaire for each subject. RESULTS:
      MC patients had a significantly higher risk of occupational exposure (OR 5.6; 95%
      CI 1.84-17.50) than controls. ESEM evaluation revealed a significantly higher
      concentration, expressed as number of positive spots (NS), of serum inorganic
      particles in MC patients compared with controls (mean NS 18, SD = 16 versus NS
      5.4, SD = 5.1; P < 0.05). Cryoprecipitate samples of MC patients showed high
      concentrations of inorganic particles (mean NS 49, SD = 19). We found a strong
      correlation between NS and cryocrit (i.e. percentage of cryoprecipitate/total
      serum after centrifugation at 4 degrees C) levels (P < 0.001). CONCLUSIONS: In
      addition to HCV infection, MPs and NPs might play an important role in the
      aetiopathogenesis of MC.

PMID- 27694374
TI  - Challenging cognitive cases among physician populations: case vignettes and
      recommendations.
AB  - BACKGROUND: Physicians are not immune to cognitive impairment. Because of the
      risks created by practising doctors with these issues, some have suggested
      developing objective, population-specific measures of evaluation and screening
      guidelines to assess dysfunction. However, there is very little published
      information from which to construct such resources. AIMS: To highlight the
      presentation characteristics and provide evaluation recommendations specific to
      the needs of physicians with actual or presumed cognitive impairment. METHODS: A
      retrospective database and chart review of cognitively impaired doctors who
      presented to a physician health programme (PHP). Complex cases were highlighted
      using simple descriptives and clinical vignettes. RESULTS: A total of 124 cases
      were included. Clients presented with a variety of issues other than cognitive
      concerns. We identified four principal domains of impairment: (i) diseases of (or
      in) the brain (48%); (ii) mood/ anxiety disorders or treatment side effects
      (28%); (iii) substance use (9%) and (iv) traumatic brain injury (7%). Age was not
      a good predictor of impairment and brief screening using the Montreal Cognitive
      Assessment demonstrated a ceiling effect with this cohort. Although many clients
      underwent some type of professional or personal transition, impairment did not
      necessarily indicate worse functioning after care. CONCLUSIONS: Physician
      cognitive evaluations should consider a variety of secondary sources of
      information, particularly vocational performance reports. It may take time before
      cognitive impairment can be diagnosed or ruled-out in this population. Prior
      assumptions, especially for non-cognitive referrals, can lead to inaccurate
      diagnosis and referrals. PHPs must manage cognitive cases carefully, not only in
      their clinical complexity but also in their psychosocial aspects.

PMID- 27694375
TI  - Squatting-induced bilateral peroneal nerve palsy in a sewer pipe worker.
AB  - Compression neuropathy of the common peroneal nerve (CPN) at the fibula head is a
      common condition, but it has not attracted attention in working environments.
      Here, we report a 38-year-old sewer pipe worker who presented with bilateral CPN
      palsy following 6h working with a squatting posture in a narrow sewer pipe.
      During the work, he could not stretch his legs sufficiently because of the
      confined space. His symptoms deteriorated with repetition of the same work for 1
      week. Motor nerve conduction study showed conduction block at the fibula head of
      bilateral CPNs, compatible with compression neuropathy at this lesion. Three
      months after cessation of work requiring the causative posture, his symptoms and
      neurophysiological abnormalities had resolved completely. Almost all seven of his
      co-workers presented transiently with similar and milder symptoms, although one
      showed CPN palsy for 6 months. Prolonged squatting posture in a confined space
      causes acute compression neuropathy at the fibula head in the CPN. More attention
      should be paid to 'confined space worker's compression neuropathy'.

PMID- 27694377
TI  - Obesity prevalence and accuracy of BMI-defined obesity in Russian firefighters.
AB  - BACKGROUND: No data exist on obesity or the accuracy of body mass index (BMI) in
      Russian Federation firefighters. AIMS: To determine the prevalence of obesity and
      rates of misclassification of BMI-based obesity status. METHODS: Career
      firefighters in the Moscow region completed anthropometric assessments including
      height, weight, BMI, body fat per cent (BF%) and waist circumference (WC). Using
      these three methods, we defined obesity as BMI >=30, BF% >25 and WC >102,
      respectively. RESULTS: The study group consisted of 167 male firefighters.
      Obesity prevalence was 22% for BMI [95% confidence interval (CI) 16.9-28.5], 60%
      for BF% (95% CI 52.5-67.3) and 28% for WC (95% CI 21.3-34.9). False positive
      rates for BMI-based obesity status were low, with 3% (95% CI -1.1 to 7.1) and 6%
      (95% CI 1.6-9.9) of non-obese participants defined by BF% and WC standards
      misidentified as obese using BMI. However, 65% (95% CI 55.7-77.4) of BF%-defined
      obese participants and 36% (95% CI 22.5-49.9) of WC-defined obese participants
      were misclassified as non-obese using BMI (i.e. false negatives). CONCLUSIONS:
      Rates of BMI-based obesity in Russian male firefighters were similar to that of
      males in the general Russian adult male population. Compared with BF% or WC
      standards, BMI-based obesity classi- fication produced low rates of false
      positives but demonstrated high rates of false negatives.

PMID- 27694376
TI  - Shift work, mental distress and job satisfaction among Palestinian nurses.
AB  - BACKGROUND: Associations between shift work (SW) schedules, mental distress and
      job satisfaction have never been completely described. AIMS: To examine gender
      specific associations of SW with mental distress and job satisfaction in nurses
      in Hebron District, Palestine, in 2012. METHODS: Detailed information on work
      schedules (day versus shift), socio-demographic status, mental distress (General
      Health Questionnaire, GHQ-30) and job satisfaction (Generic Job Satisfaction
      Scale) in nurses employed in Hebron District, Palestine, was obtained through a
      questionnaire survey. Associations of SW and outcomes were examined by linear
      regression analysis. RESULTS: Of 372 nurses eligible for the study, 309 and 338
      completed surveys regarding mental distress and job satisfaction, respectively.
      The sample comprised 62% women and 38% men. After adjusting for covariates, women
      working shifts reported significantly higher levels of mean mental distress [beta
      coefficient 3.6; 95% confidence interval (CI) 0.3-7.0] compared with women
      working regular day shifts. Men working shifts reported significantly lower
      levels of job satisfaction (-3.3; 95% CI -6.2 to -0.5) than men working regular
      day shifts. Women reported higher levels of mental distress than men, but this
      was unrelated to work schedule. CONCLUSIONS: In this study, nurses working shifts
      reported higher levels of mental distress and lower levels of job satisfaction,
      although these associations were weaker when adjusted for potential covariates.
      There was no evidence of a gender differential in the association between SW and
      mental distress and job satisfaction.

PMID- 27694378
TI  - Incidence of tuberculosis among nurses and healthcare assistants in France.
AB  - BACKGROUND: Health care workers (HCWs) are considered to be at higher risk of
      tuberculosis (TB) than the general population. However, a decreasing incidence in
      the general population as well as improvement in preventive measures in hospitals
      has reduced the risk for HCWs. AIMS: To quantify the actual incidence of TB in
      nurses and health care assistants in a low-incidence country. METHODS: We
      performed a retrospective study of 80 hospitals throughout France, employing
      233389 health care staff (physicians excluded). We calculated the number of
      pulmonary TB cases over 3 years (700166 person-years) and the total number of
      staff members in each job category (nurses, health care assistants,
      administrative staff) in each hospital, to calculate the incidence. RESULTS:
      Overall, the incidence rate varied between 1.27 and 6/100000 for administrative
      staff and nurses, respectively (non-significant difference). The incidence varied
      according to the geographical area. However, the incidence in nurses and health
      care assistants was not different from the general population (7.5/100000).
      CONCLUSIONS: In a low-incidence country, such as France, the implementation of
      measures to prevent occupational TB among HCWs has been effective. These
      preventive measures should be maintained but medical follow-up could be revised.

PMID- 27694379
TI  - Cancer Drugs Remain Hot Targets.
AB  - Estimates of future growth in the oncology market, a predicted increase of 11%
      per year in sales, and the need to expand drug-development pipelines to sustain
      profits have been driving up the value of corporate mergers, such as Pfizer's
      purchase of Medivation for $14 billion.

PMID- 27694388
TI  - Secondary structure model of the naked segment 7 influenza A virus genomic RNA.
AB  - The influenza A virus (IAV) genome comprises eight negative-sense viral (v)RNA
      segments. The seventh segment of the genome encodes two essential viral proteins
      and is specifically packaged alongside the other seven vRNAs. To gain insights
      into the possible roles of RNA structure both within and without virions, a
      secondary structure model of a naked (protein-free) segment 7 vRNA (vRNA7) has
      been determined using chemical mapping and thermodynamic energy minimization. The
      proposed structure model was validated using microarray mapping, RNase H cleavage
      and comparative sequence analysis. Additionally, the detailed structures of three
      vRNA7 fragment constructs - comprising independently folded subdomains - were
      determined. Much of the proposed vRNA7 structure is preserved between IAV
      strains, suggesting their importance in the influenza replication cycle. Possible
      structure rearrangements, which allow or preclude long-range RNA interactions,
      are also proposed.

PMID- 27694387
TI  - The topogenic function of S4 promotes membrane insertion of the voltage-sensor
      domain in the KvAP channel.
AB  - Voltage-dependent K+ (KV) channels control K+ permeability in response to shifts
      in the membrane potential. Voltage sensing in KV channels is mediated by the
      positively charged transmembrane domain S4. The best-characterized KV channel,
      KvAP, lacks the distinct hydrophilic region corresponding to the S3-S4
      extracellular loop that is found in other K+ channels. In the present study, we
      evaluated the topogenic properties of the transmembrane regions within the
      voltage-sensing domain in KvAP. S3 had low membrane insertion activity, whereas
      S4 possessed a unique type-I signal anchor (SA-I) function, which enabled it to
      insert into the membrane by itself. S4 was also found to function as a stop
      transfer signal for retention in the membrane. The length and structural nature
      of the extracellular S3-S4 loop affected the membrane insertion of S3 and S4,
      suggesting that S3 membrane insertion was dependent on S4. Replacement of charged
      residues within the transmembrane regions with residues of opposite charge
      revealed that Asp72 in S2 and Glu93 in S3 contributed to membrane insertion of S3
      and S4, and increased the stability of S4 in the membrane. These results indicate
      that the SA-I function of S4, unique among K+ channels studied to date, promotes
      the insertion of S3 into the membrane, and that the charged residues essential
      for voltage sensing contribute to the membrane-insertion of the voltage sensor
      domain in KvAP.

PMID- 27694385
TI  - Tumor Cell-Independent Estrogen Signaling Drives Disease Progression through
      Mobilization of Myeloid-Derived Suppressor Cells.
AB  - : The role of estrogens in antitumor immunity remains poorly understood. Here, we
      show that estrogen signaling accelerates the progression of different estrogen
      insensitive tumor models by contributing to deregulated myelopoiesis by both
      driving the mobilization of myeloid-derived suppressor cells (MDSC) and enhancing
      their intrinsic immunosuppressive activity in vivo Differences in tumor growth
      are dependent on blunted antitumor immunity and, correspondingly, disappear in
      immunodeficient hosts and upon MDSC depletion. Mechanistically, estrogen receptor
      alpha activates the STAT3 pathway in human and mouse bone marrow myeloid
      precursors by enhancing JAK2 and SRC activity. Therefore, estrogen signaling is a
      crucial mechanism underlying pathologic myelopoiesis in cancer. Our work suggests
      that new antiestrogen drugs that have no agonistic effects may have benefits in a
      wide range of cancers, independently of the expression of estrogen receptors in
      tumor cells, and may synergize with immunotherapies to significantly extend
      survival. SIGNIFICANCE: Ablating estrogenic activity delays malignant progression
      independently of the tumor cell responsiveness, owing to a decrease in the
      mobilization and immunosuppressive activity of MDSCs, which boosts T-cell
      dependent antitumor immunity. Our results provide a mechanistic rationale to
      block estrogen signaling with newer antagonists to boost the effectiveness of
      anticancer immunotherapies. Cancer Discov; 7(1); 72-85. (c)2016 AACR.See related
      commentary by Welte et al., p. 17This article is highlighted in the In This Issue
      feature, p. 1.

PMID- 27694386
TI  - Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer.
AB  - : Amplified and/or mutated MET can act as both a primary oncogenic driver and as
      a promoter of tyrosine kinase inhibitor (TKI) resistance in non-small cell lung
      cancer (NSCLC). However, the landscape of MET-specific targeting agents remains
      underdeveloped, and understanding of mechanisms of resistance to MET TKIs is
      limited. Here, we present a case of a patient with lung adenocarcinoma harboring
      both a mutation in EGFR and an amplification of MET, who after progression on
      erlotinib responded dramatically to combined MET and EGFR inhibition with
      savolitinib and osimertinib. When resistance developed to this combination, a new
      MET kinase domain mutation, D1228V, was detected. Our in vitro findings
      demonstrate that METD1228V induces resistance to type I MET TKIs through impaired
      drug binding, while sensitivity to type II MET TKIs is maintained. Based on these
      findings, the patient was treated with erlotinib combined with cabozantinib, a
      type II MET inhibitor, and exhibited a response. SIGNIFICANCE: With several
      structurally distinct MET inhibitors undergoing development for treatment of
      NSCLC, it is critical to identify mechanism-based therapies for drug resistance.
      We demonstrate that an acquired METD1228V mutation mediates resistance to type I,
      but not type II, MET inhibitors, having therapeutic implications for the clinical
      use of sequential MET inhibitors. Cancer Discov; 6(12); 1334-41. (c)2016 AACR.See
      related commentary by Trusolino, p. 1306This article is highlighted in the In
      This Issue feature, p. 1293.

PMID- 27694389
TI  - Membrane protein extraction and purification using styrene-maleic acid (SMA)
      copolymer: effect of variations in polymer structure.
AB  - The use of styrene-maleic acid (SMA) copolymers to extract and purify
      transmembrane proteins, while retaining their native bilayer environment,
      overcomes many of the disadvantages associated with conventional detergent-based
      procedures. This approach has huge potential for the future of membrane protein
      structural and functional studies. In this investigation, we have systematically
      tested a range of commercially available SMA polymers, varying in both the ratio
      of styrene and maleic acid and in total size, for the ability to extract, purify
      and stabilise transmembrane proteins. Three different membrane proteins (BmrA,
      LeuT and ZipA), which vary in size and shape, were used. Our results show that
      several polymers, can be used to extract membrane proteins, comparably to
      conventional detergents. A styrene:maleic acid ratio of either 2:1 or 3:1,
      combined with a relatively small average molecular mass (7.5-10 kDa), is optimal
      for membrane extraction, and this appears to be independent of the protein size,
      shape or expression system. A subset of polymers were taken forward for
      purification, functional and stability tests. Following a one-step affinity
      purification, SMA 2000 was found to be the best choice for yield, purity and
      function. However, the other polymers offer subtle differences in size and
      sensitivity to divalent cations that may be useful for a variety of downstream
      applications.

PMID- 27694390
TI  - Can Red Blood Cell Indices Act as Surrogate Markers for Discordance between
      Hemoglobin A1c and Fasting Blood Glucose?

PMID- 27694391
TI  - Using Targeted Sequencing of Paralogous Sequences for Noninvasive Detection of
      Selected Fetal Aneuploidies.
AB  - BACKGROUND: Current methods for noninvasive prenatal testing (NIPT) ascertain
      fetal aneuploidies using either direct counting measures of DNA fragments from
      specific genomic regions or relative measures of single nucleotide polymorphism
      frequencies. Alternatively, the ratios of paralogous sequence pairs were
      predicted to reflect fetal aneuploidy. We developed a NIPT assay that uses
      paralog sequences to enable noninvasive detection of fetal trisomy 21 (T21) and
      trisomy 18 (T18) using cell-free DNA (cfDNA) from maternal plasma. METHODS: A
      total of 1060 primer pairs were designed to determine fetal aneuploidy status,
      fetal sex, and fetal fraction. Each library was prepared from cfDNA by
      coamplifying all 1060 target pairs together in a single reaction well. Products
      were measured using massively parallel sequencing and deviations from expected
      paralog ratios were determined based on the read depth from each paralog.
      RESULTS: We evaluated this assay in a blinded set of 480 cfDNA samples with fetal
      aneuploidy status determined by the MaterniT21(r) PLUS assay. Samples were
      sequenced (mean = 2.3 million reads) with 432 samples returning a result. Using
      the MaterniT21 PLUS assay for paired plasma aliquots from the same individuals as
      a reference, all 385 euploid samples, all 31 T21 samples, and 14 of 16 T18
      samples were detected with no false positive results observed. CONCLUSIONS: This
      study introduces a novel NIPT aneuploidy detection approach using targeted
      sequencing of paralog motifs and establishes proof-of-concept for a potentially
      low-cost, highly scalable method for the identification of selected fetal
      aneuploidies with performance and nonreportable rate similar to other published
      methods.

PMID- 27694393
TI  - Stable-Isotope Dilution HPLC-Electrospray Ionization Tandem Mass Spectrometry
      Method for Quantifying Hydroxyurea in Dried Blood Samples.
AB  - BACKGROUND: Sickle cell anemia (SCA) is a life-threatening blood disorder
      characterized by the presence of sickle-shaped erythrocytes. Hydroxyurea is
      currently the only US Food and Drug Administration-approved treatment and there
      is a need for a convenient method to monitor compliance and hydroxyurea
      concentrations, especially in pediatric SCA patients. METHODS: We describe a
      novel approach to the determination of hydroxyurea concentrations in dried whole
      blood collected on DMPK-C cards or volumetric absorptive microsampling (VAMS)
      devices. Hydroxyurea was quantified by electrospray ionization LC-MS/MS using
      [13C15N2]hydroxyurea as the internal standard. Calibrators were prepared in whole
      blood applied to DMPK-C cards or VAMS devices. RESULTS: Calibration curves for
      blood hydroxyurea measured from DMPK-C cards and VAMS devices were linear over
      the range 0.5-60 MUg/mL. Interassay and intraassay CVs were <15% for blood
      collected by both methods, and the limit of detection was 5 ng/mL. Whole blood
      hydroxyurea was stable for up to 60 days on DMPK-C cards and VAMS devices when
      frozen at -20  degrees C or -80  degrees C. Whole blood hydroxyurea
      concentrations in samples collected on DMPK-C cards or VAMS devices from SCA
      patients were in close agreement. CONCLUSIONS: This tandem mass spectrometry
      method permits measurement of hydroxyurea concentrations in small volumes of
      dried blood applied to either DMPK-C cards or VAMS devices with comparable
      performance. This method for measuring hydroxyurea from dried blood permits the
      evaluation of therapeutic drug monitoring, individual pharmacokinetics, and
      medication adherence using heel/finger-prick samples from pediatric patients with
      SCA treated with hydroxyurea.

PMID- 27694392
TI  - Short-term Variability of Vitamin D-Related Biomarkers.
AB  - BACKGROUND: Quantifying the variability of biomarkers is important, as high
      within-person variability can lead to misclassification of individuals. Short
      term variability of important markers of vitamin D metabolism is relatively
      unknown. METHODS: A repeatability study was conducted in 160 Atherosclerosis Risk
      in Communities study participants (60% female, 28% black, mean age 76 years).
      Fasting serum was drawn at 2 time points, a median of 6 (range 3-13) weeks apart.
      Vitamin D binding protein (VDBP) and 25-hydroxyvitamin D [25(OH)D] were measured
      by LC-MS, fibroblast growth factor (FGF23) and parathyroid hormone (PTH) by
      enzyme-linked immunoassay, and calcium and phosphorus by Roche Cobas 6000. Free
      and bioavailable 25(OH)D were calculated. We calculated the within-person CV
      (CVW), intraclass correlation coefficient (ICC), Spearman rank correlation
      coefficient (r), and percent reclassified. RESULTS: The CVW was lowest for
      calcium (2.0%), albumin (3.6%), 25(OH)D (6.9%), VDBP (7.0%) and phosphorus
      (7.6%); intermediate for free 25(OH)D (9.0%) and bioavailable 25(OH)D (9.9%); and
      highest for PTH (16.7%) and FGF23 (17.8%). Reclassification was highest for PTH,
      VDBP, and phosphorus (all 7.5%). The ICC and r were highest (>=0.80) for 25(OH)D,
      free 25(OH)D, bioavailable 25(OH)D and PTH, but somewhat lower (approximately
      0.60-0.75) for the other biomarkers. CONCLUSIONS: Six-week short-term
      variability, as assessed by CVW, was quite low for VDBP, calcium and phosphorus,
      but fairly high for FGF23 and PTH. As such, multiple measurements of FGF23 and
      PTH may be needed to minimize misclassification. These results provide insight
      into the extent of potential misclassification of vitamin D markers in research
      and clinical settings.

PMID- 27694394
TI  - Focus on Ecophysiology.

PMID- 27694395
TI  - A Fresh Look at the Role of Auxin in PIN Trafficking.

PMID- 27694396
TI  - CORRECTION: Vol. 171: 2516-2535, 2016.

PMID- 27694397
TI  - CORRECTION: Vol. 142: 1193-1201, 2006.

PMID- 27694398
TI  - CORRECTION: Vol. 171: 1182-1191, 2016.

PMID- 27694399
TI  - Is the infant car seat challenge useful? A pilot study in a simulated moving
      vehicle.
AB  - BACKGROUND AND OBJECTIVE: The American Academy of Pediatrics recommends that
      preterm infants complete a predischarge 'car seat challenge' observation for
      cardiorespiratory compromise while in a car seat. This static challenge does not
      consider the more upright position in a car or the vibration of the seat when the
      car is moving. This pilot study was designed to assess the cardiorespiratory
      effects of vibration, mimicking the effect of being in a moving car, on preterm
      and term infants. METHODS: A simulator was designed to reproduce vertical
      vibration similar to that in a rear-facing car seat at 30 mph. 19 healthy newborn
      term and 21 preterm infants, ready for hospital discharge, underwent
      cardiorespiratory measurements while lying flat in a cot (baseline), static in
      the seat (30 degrees ), simulator (40 degrees ) and during motion (vibration 40
      degrees ). RESULTS: Median test age was 13 days (range 1-65 days) and median
      weight was 2.5 kg (IQR: 2.1-3.1 kg).Compared with baseline observations, only the
      total number of desaturations was significantly increased when infants were
      placed at 30 degrees  (p=0.03). At 40 degrees , or with vibration, respiratory
      and heart rates increased and oxygen saturation decreased significantly. Profound
      desaturations <85% significantly increased during motion, regardless of
      gestational age. CONCLUSIONS: This is the first study to assess the effect of
      motion on infants seated in a car safety seat. Term and preterm infants showed
      significant signs of potentially adverse cardiorespiratory effects in the upright
      position at 40 degrees , particularly with simulated motion, not identified in
      the standard challenge. A larger study is required to investigate the
      significance of these results.

PMID- 27694400
TI  - An Epidemiological Study of Burglary Offenders: Trends and Predictors of Self
      Reported Arrests for Burglary in the United States, 2002-2013.
AB  - Burglary is serious property crime with a relatively high incidence and has been
      shown to be variously associated with other forms of criminal behavior.
      Unfortunately, an epidemiological understanding of burglary and its correlates is
      largely missing from the literature. Using public-use data collected between 2002
      and 2013 as part of the National Survey on Drug Use and Health (NSDUH), the
      current study compared those who self-reported burglary arrest in the prior 12
      months with and without criminal history. The unadjusted prevalence estimates of
      self-reported burglary arrest were statistically different for those with a prior
      arrest history (4.7%) compared with those without an arrest history (0.02%) which
      is a 235-fold difference. Those with an arrest history were more likely to report
      lower educational attainment, to have lower income, to have moved more than 3
      times in the past 5 years, and to use alcohol, tobacco, illicit drugs, and engage
      in binge drinking. Moreover, those with prior arrest histories were younger and
      more likely to be male. There is considerable heterogeneity among burglars with
      criminal history indicating substantially greater behavioral risk.

PMID- 27694401
TI  - Analysis of the logic and framing of a tobacco industry campaign opposing
      standardised packaging legislation in New Zealand.
AB  - BACKGROUND: The tobacco industry routinely opposes tobacco control policies,
      often using a standard repertoire of arguments. Following proposals to introduce
      standardised packaging in New Zealand (NZ), British American Tobacco New Zealand
      (BATNZ) launched the 'Agree-Disagree' mass media campaign, which coincided with
      the NZ government's standardised packaging consultations. This study examined the
      logic of the arguments presented and rhetorical strategies employed in the
      campaign. METHODS: We analysed each advertisement to identify key messages,
      arguments and rhetorical devices, then examined the arguments' structure and
      assessed their logical soundness and validity. RESULTS: All advertisements
      attempted to frame BATNZ as reasonable, and each contained flawed arguments that
      were either unsound or based on logical fallacies. Flawed arguments included
      misrepresenting the intent of the proposed legislation (straw man), claiming
      standardised packaging would harm all NZ brands (false dilemma), warning NZ not
      to adopt standardised packaging because of its Australian origins (an unsound
      argument) or using vague premises as a basis for claiming negative outcomes
      (equivocation). CONCLUSIONS: BATNZ's Agree-Disagree campaign relied on unsound
      arguments, logical fallacies and rhetorical devices. Given the industry's
      frequent recourse to these tactics, we propose strategies based on our study
      findings that can be used to assist the tobacco control community to counter
      industry opposition to standardised packaging. Greater recognition of logical
      fallacies and rhetorical devices employed by the tobacco industry will help
      maintain focus on the health benefits proposed policies will deliver.

PMID- 27694402
TI  - The effect of ankle posture on the load pathway through the hindfoot.
AB  - The foot-ankle complex is frequently injured in a wide array of debilitating
      events such as car crashes. Numerical models and experimental tests have been
      used to assess injury risk, but most do not account for the variations in ankle
      posture that frequently occur during these events. In this study, the positions
      of the bones of the foot-ankle complex (particularly, the hindfoot) were
      quantified over a range of postures. Computed tomography scans were taken of a
      male cadaveric leg under axial loading with the ankle in five postures in which
      fractures are commonly reported. The difference in the location of the talus and
      calcaneus between the neutral and each repositioned posture was quantified, and
      substantial rotations and displacements were observed for all postures tested
      (talus: 3 degrees -21.5 degrees , 1.5-10.5 mm; calcaneus: 10 degrees -20 degrees
      , 1.5-24.5 mm). Strains were also recorded at six locations on bones of the ankle
      during testing and were found to be highest in the calcaneus during inversion
      external rotation and highest in the talus during eversion-external rotation.
      Postural changes likely affect the load pathway of the foot-ankle complex,
      potentially altering the stress and strain fields from that of the neutral case
      and changing the location of fracture. This highlights the need for injury
      predicting studies examining the effect of these positional changes and to
      develop revised injury criteria accounting for the most vulnerable conditions.

PMID- 27694404
TI  - Type D personality and periodontal disease in university students: A prospective
      cohort study.
AB  - The purpose of this prospective cohort study was to investigate whether Type D
      personality was related to periodontal disease in Japanese university students.
      Among students ( n = 600) who were interested in receiving oral health
      examinations, logistic regression analysis showed that the risk of developing
      periodontal disease during a 3-year period was associated with body mass index ?
      25 (odds ratio: 2.543; 95% confidence interval: 1.297-4.989; p = 0.007) and Type
      D personality (odds ratio: 1.473; 95% confidence interval: 1.027-2.111; p =
      0.035). In this short-term prospective cohort study, a significant association
      between periodontal disease and Type D personality was observed in Japanese
      university students.

PMID- 27694403
TI  - Analysis on the Complete Mitochondrial Genome of Andraca theae (Lepidoptera:
      Bombycoidea).
AB  - The bombycid moth, Andraca theae (Matsumura) (Lepidoptera: Bombycoidea) is an
      important pest of tea in southeastern China. In the present study, the
      mitochondrial genome (mitogenome) of A. theae was amplified by polymerase chain
      reaction and sequenced. The complete mitogenome of A. theae, encoding 37 genes,
      was 15,737 bp in length (Genbank no. KX365419), and consisted of 13 protein
      coding genes (PCGs), 22 tRNA genes, 2 ribosomal RNA genes and an adenine (A) +
      thymine (T)-rich region (AT-rich region). The gene order of A. theae mitogenome
      was typical for Lepidoptera mitogenomes. Except for cox1, which started with CGA,
      all other 12 PCGs started with ATN. Eleven of the 13 PCGs ended with TAA, expect
      for cox1 and cox2, which ended with a single T. The maximum likelihood method and
      the Bayesian method were used to analyze the phylogenetic relationship among 22
      representative bombycoid species with a matrix consisting of the 13 PCGs of the
      mitogenomes of the 22 species. The topological structures of the two phylogenetic
      trees we constructed were almost identical, with the results indicating that the
      bombycid species, including A. theae, clustered into a single clade with a
      bootstrap value of 58% and a posterior probability of 0.98. The phylogenetic
      relationship among the Bombycoidea species analyzed was Lasiocampidae +
      (Bombycidae + (Saturniidae + Sphingidae)) which was supported by a high bootstrap
      value of 100% and a posterior probability of 1.00.

PMID- 27694405
TI  - European Colonization, Not Polynesian Arrival, Impacted Population Size and
      Genetic Diversity in the Critically Endangered New Zealand Kakapo.
AB  - Island endemic species are often vulnerable to decline and extinction following
      human settlement, and the genetic study of historical museum specimens can be
      useful in understanding these processes. The kakapo (Strigops habroptilus) is a
      critically endangered New Zealand parrot that was formerly widespread and
      abundant. It is well established that both Polynesian and European colonization
      of New Zealand impacted the native avifauna, but the timeframe and severity of
      impacts have differed depending on species. Here, we investigated the relative
      importance of the 2 waves of human settlement on kakapo decline, using
      microsatellites and mitochondrial DNA (mtDNA) to characterize recent kakapo
      genetic and demographic history. We analyzed samples from 49 contemporary
      individuals and 54 museum specimens dating from 1884 to 1985. Genetic diversity
      decreased significantly between historical and contemporary kakapo, with a
      decline in mean number of microsatellite alleles from 6.15 to 3.08 and in number
      of mtDNA haplotypes from 17 to 3. Modeling of demographic history indicated a
      recent population bottleneck linked to the period of European colonization
      (approximately 5 generations ago) but did not support a major decline linked to
      Polynesian settlement. Effective population size estimates were also larger for
      historical than contemporary kakapo. Our findings inform contemporary kakapo
      management by indicating the timeframe and possible cause of the bottleneck,
      which has implications for the management of extant genetic diversity. We
      demonstrate the broader utility of a historical perspective in understanding
      causes of decline and managing extinction risk in contemporary endangered
      species.

PMID- 27694406
TI  - A new alphabet for COPD care.

PMID- 27694407
TI  - What can we learn from blood granulocyte patterns in patients with asthma?

PMID- 27694408
TI  - Interleukin-6 as a biomarker for asthma: hype or is there something else?

PMID- 27694409
TI  - Why should we care about upper airway inflammation in obstructive sleep apnoea?

PMID- 27694410
TI  - Corticosteroids for community-acquired pneumonia: a critical view of the
      evidence.

PMID- 27694411
TI  - Towards a molecular classification of pulmonary arterial hypertension.

PMID- 27694413
TI  - Asthma and risk of bronchiectasis exacerbation: we still need more evidence.

PMID- 27694414
TI  - Asthma and risk of bronchiectasis exacerbation: we still need more evidence.

PMID- 27694415
TI  - Obstructive sleep apnoea and bone health.

PMID- 27694416
TI  - Obstructive sleep apnoea and bone health.

PMID- 27694417
TI  - Pulmonary mucosa-associated lymphoid tissue lymphoma revisited.

PMID- 27694418
TI  - Pulmonary mucosa-associated lymphoid tissue lymphoma revisited.

PMID- 27694419
TI  - Tuberculosis screening yield of asylum seekers in Europe.

PMID- 27694420
TI  - Tuberculosis screening yield of asylum seekers in Europe.

PMID- 27694422
TI  - ERJ October Podcast: blood eosinophil count as a biomarker in patients with
      airway disease.

PMID- 27694421
TI  - Comprehensive cost of treating one patient with MDR/pre-XDR-TB in Wellington, New
      Zealand.

PMID- 27694423
TI  - Posttransplant Lymphoproliferative Disorders in Neuronal Xenotransplanted
      Macaques.
AB  - Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of
      lymphoid proliferations that occur in the setting of depressed T-cell function
      due to immunosuppressive therapy used following solid organ transplantation,
      hematopoietic stem cell transplantation, and also xenotransplantation. In the
      present study, 28 immunosuppressed parkinsonian Macaca fascicularis were
      intracerebrally injected with wild-type or CTLA4-Ig transgenic porcine xenografts
      to identify a suitable strategy to enable long-term cell survival, maturation,
      and differentiation. Nine of 28 (32%) immunosuppressed primates developed masses
      compatible with PTLD, located mainly in the gastrointestinal tract and/or nasal
      cavity. The masses were classified as monomorphic PTLD according to the World
      Health Organization classification. Immunohistochemistry and polymerase chain
      reaction (PCR) analyses revealed that the PTLDs were associated with macaca
      lymphocryptovirus as confirmed by double-labeling immunohistochemistry for CD20
      and Epstein-Barr nuclear antigen 2 (EBNA-2), where the viral protein was located
      within the CD20+ neoplastic B cells. In sera from 3 distinct phases of the
      experimental life of the primates, testing by quantitative PCR revealed a
      progression of the viral load that paralleled the PTLD progression and no
      evidence of zoonotic transmission of porcine lymphotropic herpesvirus through
      xenoneuronal grafts. These data suggest that monitoring the variation of macaca
      lymphocryptovirus DNA in primates could be used as a possible early diagnostic
      tool for PTLD progression, allowing preemptive treatment such as
      immunosuppression therapy reduction.

PMID- 27694424
TI  - Ocular Lesions in Red-Tailed Hawks ( Buteo jamaicensis) With Naturally Acquired
      West Nile Disease.
AB  - Ocular lesions are common in red-tailed hawks with West Nile (WN) disease. These
      lesions consist of pectenitis, choroidal or retinal inflammation, or retinal
      necrosis, but detailed investigation of the ocular lesions is lacking. Postmortem
      examination of the eyes of 16 red-tailed hawks with naturally acquired WN disease
      and 3 red-tailed hawks without WN disease was performed using histopathology,
      immunohistochemistry for West Nile virus (WNV) antigen, glial fibrillary acid
      protein, cleaved caspase-3, and the terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling method. Retinal lesions were classified as type I
      or type II lesions. Type I lesions were characterized by lymphoplasmacytic
      infiltrates in the subjacent choroid with degeneration limited to the outer
      retina (type Ia lesion) or with degeneration and necrosis of the outer retina or
      outer and inner retina (type Ib lesion) while retinal collapse, atrophy, and
      scarring were hallmarks of type II lesions. Type II retinal lesions were
      associated with a more pronounced choroiditis. Although not statistically
      significant, WNV antigen tended to be present in larger quantity in type Ib
      lesions. Type I lesions are considered acute while type II lesions are chronic.
      The development of retinal lesions was associated with the presence of an
      inflammatory infiltrate in the choroid. A breakdown of the blood-retina barrier
      is suspected to be the main route of infection of the retina. Within the retina,
      virus appeared to spread via both neuronal and Muller cell processes.

PMID- 27694425
TI  - Left Ventricular Apical Aneurysm in a Cat With Primary Cardiomyopathy.
AB  - A 13-year-old female Persian cat died suddenly after severe respiratory distress.
      At necropsy, the changes were compatible with congestive heart failure. The heart
      was enlarged with a flabby and puckered sac-like aneurysm at the apex of the left
      ventricle. The apical zone showed a thin muscular wall arising from the free wall
      of the left ventricle connected to a bulged saccular area through a wide
      communication. Microscopically, the wall of the aneurysm was composed of fibrous
      connective tissue with neovascularization and sparse atrophied myocardial cells
      at the margins. A few isolated cardiomyocytes in the lesion stained positively
      for desmin, and the inner lining of the aneurysm had immunoreactivity to von
      Willebrand factor and CD31. Mature fibrous connective tissue was interspersed
      with degenerated and disorganized cardiomyocytes elsewhere in the myocardium, and
      many small myocardial arteries were tortuous and thickened. In this case of
      sudden death, the diagnosis was primary cardiomyopathy, with formation of a left
      ventricular apical aneurysm within an area of marked myocardial fibrosis and
      cardiomyocyte atrophy.

PMID- 27694426
TI  - Pathologic Findings and Viral Antigen Distribution During Natural Infection of
      Ring-Necked Pheasants With H5N2 Highly Pathogenic Avian Influenza Virus A.
AB  - Highly pathogenic avian influenza (HPAI) is a major viral disease of poultry
      characterized by acute onset, systemic infection, and rapid death. In January
      2015, H5N2 HPAI was identified by quantitative reverse transcriptase polymerase
      chain reaction (qRT-PCR) and gene sequencing as the cause of rapid death in 40 of
      390 ring-necked pheasants (approximately 10% mortality), raised in a game bird
      farm in Washington State. We report clinicopathologic findings and viral antigen
      distribution in pheasants that died during the outbreak. Affected birds were
      depressed with reluctance to move, ruffled feathers, and drooping heads.
      Congestion of the cerebellar meningeal blood vessels was the only consistent
      gross pathologic finding. Meningoencephalitis with vasculitis and necrosis in the
      spleen and heart were the major microscopic lesions in the birds. Viral antigen
      was consistently detected in the brain, heart, and ovary with variable presence
      in other organs.

PMID- 27694427
TI  - Barriers to Medical Error Reporting for Physicians and Nurses.
AB  - The purpose of the study was to determine what barriers to error reporting exist
      for physicians and nurses. The study, of descriptive qualitative design, was
      conducted with physicians and nurses working at a training and research hospital.
      In-depth interviews were held with eight physicians and 15 nurses, a total of 23
      participants. Physicians and nurses do not choose to report medical errors that
      they experience or witness. When barriers to error reporting were examined, it
      was seen that there were four main themes involved: fear, the attitude of
      administration, barriers related to the system, and the employees' perceptions of
      error. It is important in terms of preventing medical errors to identify the
      barriers that keep physicians and nurses from reporting errors.

PMID- 27694428
TI  - Cardiorespiratory fitness testing and cardiovascular disease risk in male
      steelworkers.
AB  - BACKGROUND: The workplace has been advocated as a setting to perform
      cardiovascular disease (CVD) risk assessments. These risk assessments usually
      focus on traditional risk factors rather than cardiorespiratory fitness (CRF)
      despite established associations between CRF and CVD. The lack of guidance on
      interpreting health-related CRF values has been suggested as a barrier to
      utilizing CRF in practice. AIMS: To assess the merits of CRF testing in the
      workplace and explore whether a CRF value identified male individuals above the
      recommended threshold for further clinical investigation. METHODS: Cross
      sectional analysis of male steelworkers from Carmarthenshire, South Wales, UK who
      completed a workplace-based CVD risk assessment with an added CRF protocol based
      on heart rate responses (Chester Step Test). Receiver operating characteristic
      (ROC) analysis was undertaken to explore the possibility of a CRF value to
      identify individuals at an increased 10-year risk of CVD (QRISK2 >= 10%).
      RESULTS: There were 81 participants. ROC analysis revealed that a CRF level of
      34.5ml/kg/min identified those individuals above the >=10% QRISK2 threshold with
      the best sensitivity (0.800) and specificity (0.687) to discriminate against true
      and false-positive rates. Further analysis revealed that individuals with either
      'Average' or 'Below Average' CRF would be five times more likely to have a 10
      year CVD risk above the >=10% QRISK2 threshold than individuals with an
      'Excellent' or 'Good' level of fitness [OR 5.10 (95% CI 1.60-16.3)]. CONCLUSIONS:
      This study suggests CRF assessments are a useful addition to a workplace CVD
      assessment and could identify male individuals at increased predicted risk of the
      condition.

PMID- 27694429
TI  - Determination of Nickel and Manganese Contaminants in Pharmaceutical Iron
      Supplements Using Energy Dispersive X-ray Fluorescence.
AB  - In this study, we investigate the capability of energy dispersive X-ray
      fluorescence (EDXF) spectrometry in a triaxial geometry apparatus as a fast and
      nondestructive determination method of both dominant and contaminant elements in
      pharmaceutical iron supplements. The following iron supplements brands with their
      respective active ingredients were analyzed: Neutrofer folico (iron gylcinate),
      Anemifer (iron(II) sulfate monohydrate), Noripurum (iron(III)-hydroxide
      polymaltose complex), Sulferbel (iron(II) sulfate monohydrate), and Combiron
      Folico (carbonyl iron). Although we observe a good agreement between the iron
      content obtained by the present method and that indicated in the supplement's
      prescribed dose, we observe contamination by manganese and nickel of up to 180
      MUg and 36 MUg, respectively. These contents correspond to 7.2% and 14.4% of the
      permitted daily exposure of manganese and nickel, respectively, for an average
      adult individual as determined by the European Medicine Agency (EMEA). The method
      was successfully validated against the concentrations of several certified
      reference materials of biological light matrices with similar concentrations of
      contaminants. Moreover, we also validated our method by comparing the
      concentrations with those obtained with the inductively coupled plasma-atomic
      emission technique.

PMID- 27694430
TI  - Background Subtraction of Raman Spectra Based on Iterative Polynomial Smoothing.
AB  - In this paper, a novel background subtraction algorithm is presented that can
      automatically recover Raman signal. This algorithm is based on an iterative
      polynomial smoothing method that highly reduces the need for experience and a
      priori knowledge. First, a polynomial filter is applied to smooth the input
      spectrum (the input spectrum is just an original spectrum at the first
      iteration). The output curve of the filter divides the original spectrum into two
      parts, top and bottom. Second, a proportion is calculated between the lowest
      point of the signal in the bottom part and the highest point of the signal in the
      top part. The proportion is a key index that decides whether to go into a new
      iteration. If a new iteration is needed, the minimum value between the output
      curve and the original spectrum forms a new curve that goes into the same filter
      in the first step and continues as another iteration until no more iteration is
      needed to finally get the background of the original spectrum. Results from the
      simulation experiments not only show that the iterative polynomial smoothing
      algorithm achieves good performance, processing time, cost, and accuracy of
      recovery, but also prove that the algorithm adapts to different background types
      and a large signal-to-noise ratio range. Furthermore, real measured Raman spectra
      of organic mixtures and non-organic samples are used to demonstrate the
      application of the algorithm.

PMID- 27694435
TI  - Role of lipid phosphate phosphatase 3 in human aortic endothelial cell function.
AB  - AIMS: Lipid phosphate phosphatase 3; type 2 phosphatidic acid phosphatase beta
      (LPP3; PPAP2B) is a transmembrane protein dephosphorylating and thereby
      terminating signalling of lipid substrates including lysophosphatidic acid (LPA)
      and sphingosine-1-phosphate (S1P). Human LPP3 possesses a cell adhesion motif
      that allows interaction with integrins. A polymorphism (rs17114036) in PPAP2B is
      associated with coronary artery disease, which prompted us to investigate the
      possible role of LPP3 in human endothelial dysfunction, a condition promoting
      atherosclerosis. METHODS AND RESULTS: To study the role of LPP3 in endothelial
      cells we used human primary aortic endothelial cells (HAECs) in which LPP3 was
      silenced or overexpressed using either wild type or mutated cDNA constructs. LPP3
      silencing in HAECs enhanced secretion of inflammatory cytokines, leucocyte
      adhesion, cell survival, and migration and impaired angiogenesis, whereas wild
      type LPP3 overexpression reversed these effects and induced apoptosis. We also
      demonstrated that LPP3 expression was negatively correlated with vascular
      endothelial growth factor expression. Mutations in either the catalytic or the
      arginine-glycine-aspartate (RGD) domains impaired endothelial cell function and
      pharmacological inhibition of S1P or LPA restored it. LPA was not secreted in
      HAECs under silencing or overexpressing LPP3. However, the intra- and extra
      cellular levels of S1P tended to be correlated with LPP3 expression, indicating
      that S1P is probably degraded by LPP3. CONCLUSIONS: We demonstrated that LPP3 is
      a negative regulator of inflammatory cytokines, leucocyte adhesion, cell
      survival, and migration in HAECs, suggesting a protective role of LPP3 against
      endothelial dysfunction in humans. Both the catalytic and the RGD functional
      domains were involved and S1P, but not LPA, might be the endogenous substrate of
      LPP3.

PMID- 27694436
TI  - Effectiveness of Two Community Health Worker Models of Tobacco Dependence
      Treatment Among Community Residents of Ohio Appalachia.
AB  - Introduction: Community health workers (CHW) may be effective in the delivery of
      tobacco dependence treatment with underserved groups. This study evaluated two
      evidence-based CHW models of treatment. It was hypothesized that smokers assigned
      to a CHW face-to-face condition would have higher abstinence at 12-month
      posttreatment than smokers enrolled in CHW referral to a state-sponsored quitline
      condition. Intrapersonal and treatment-related factors associated with abstinence
      at 12 months were determined. Methods: A group-randomized trial was conducted
      with residents of 12 Ohio Appalachian counties with counties (n = 6) randomized
      to either a CHW face-to-face (F2F) or CHW quitline (QL) condition. Both
      conditions included behavioral counseling and free nicotine replacement therapy
      for 8 weeks. Follow-up data were collected at 3-, 6-, and 12-month posttreatment.
      Biochemically validated abstinence at 12 months served as the primary outcome.
      Results: Seven hundred and seven participants were enrolled (n = 353 CHWF2F; n =
      354 CHWQL). Baseline sample characteristics did not differ by condition. Using an
      intent-to-treat analysis (85.4% retention at 12 months), 13.3% of CHWF2F
      participants were abstinent at 12 months, compared to 10.7% of CHWQL members (OR
      = 1.28; 95% confidence interval [CI] = 0.810, 2.014; p = .292). No differences in
      abstinence were noted at 3 or 6 months by condition. Age, marital status, and
      baseline levels of cigarette consumption, depressive symptoms, and self-efficacy
      for quitting in positive settings were associated with abstinence, as was
      counseling dose during treatment. Conclusions: This research adds to the body of
      science evaluating the effectiveness of CHW models of tobacco dependence
      treatment. Both approaches may offer promise in low-resource settings and
      underserved regions. Implications: This 12-county community-based group
      randomized trial in Ohio Appalachia adds to the body of science evaluating the
      effectiveness of CHW models of tobacco dependence treatment. Both CHW approaches
      may offer promise in low-resource settings and underserved regions. These
      findings are useful to national, state, and local tobacco control agencies, as
      they expand delivery of preventive health care services postadoption of the
      Affordable Care Act in the United States.

PMID- 27694437
TI  - One-Year Smoking Trajectories Among Established Adult Smokers With Low Baseline
      Motivation to Quit.
AB  - Introduction: The majority of smokers do not intend to quit in the near term,
      making unmotivated smokers a key group to target in public health efforts.
      Although it is often assumed that continuing smokers will have stable rates of
      smoking over time, limited research has addressed this issue, particularly among
      smokers not seeking treatment. In the current study, the aims were to (1)
      characterize the trajectory of naturalistic smoking among unmotivated smokers and
      (2) examine relationships between naturalistic smoking trajectories and other
      smoking-related variables. Methods: The study sample comprised 579 control-group
      (ie, untreated) smokers within a parent clinical trial, who completed a total of
      nine assessments over 1 year. Results: Trajectory modeling identified four
      smoking trajectory groups: stable (72%), shallow decreasers (20%), steep
      decreasers (5%), and increasers (3%). Membership in the decreasing groups was
      associated with higher motivation to quit, greater history of quit attempts, and
      higher cigarettes per day. Females were more likely to be in the increasing
      versus stable group. Conclusions: Findings provide needed information on
      stability and change in cigarette consumption over the course of 1 year among an
      untreated sample of smokers and identified baseline sociodemographic and smoking
      related predictors of smoking trajectory group. Refining understanding of these
      groups is critical in updating population-based tobacco policy modeling efforts
      and informing cessation induction efforts that capitalize on naturalistic changes
      in smoking rate over time. Implications: In the current study, we found that
      approximately 25% of smokers who endorsed low quit motivation at baseline reduced
      their cigarette consumption over the course of a year, while 3% increased their
      cigarette consumption and the majority of smokers (72%) maintained a stable
      pattern. Refining understanding of smoking trajectories is critical in updating
      population-based tobacco policy modeling efforts and informing cessation
      induction efforts that capitalize on naturalistic changes in smoking rate over
      time.

PMID- 27694438
TI  - Ten-Year Course of Cosmic Transcendence in Older Adults in the Netherlands.
AB  - Objectives Gerotranscendence is defined as a transition from a materialistic and
      rationalistic perspective to a more cosmic and transcendent view of life
      accompanying the aging process. Would gerotranscendence levels still increase in
      later life? The current prospective study investigates 10-year trajectories of
      cosmic transcendence (a core dimension of gerotranscendence). Methods Four
      interview cycles of the Longitudinal Aging Study Amsterdam with 3-year intervals
      from 1995 to 2006 provide data on cosmic transcendence, demographics (ages 57
      85), religiousness, health, sense of mastery, and humor coping. Data are
      available for 2,257 respondents and 1,533 respondents in multivariate models.
      Results Latent Class Growth Analysis shows three course trajectories of cosmic
      transcendence: stable high, intermediate with a decrease, and stable low. Higher
      levels are predicted by age, importance of prayer, Roman Catholic affiliation, a
      low sense of mastery, higher cognitive ability, and humor coping. Similar results
      were obtained for the respondents who died during the study ( N = 378).
      Discussion Although levels of cosmic transcendence do not show much change during
      10 years of follow-up, the oldest respondents nonetheless attain the highest
      cosmic transcendence levels. An inclination toward relativism and contemplation
      may facilitate cosmic transcendence. However, lower cognitive ability probably
      impairs the development toward cosmic transcendence.

PMID- 27694439
TI  - Mechanisms of Insertion of dCTP and dTTP Opposite the DNA Lesion O6-Methyl-2'
      deoxyguanosine by Human DNA Polymerase eta.
AB  - O6-Methyl-2'-deoxyguanosine (O6-MeG) is a ubiquitous DNA lesion, formed not only
      by xenobiotic carcinogens but also by the endogenous methylating agent S
      adenosylmethionine. It can introduce mutations during DNA replication, with
      different DNA polymerases displaying different ratios of correct or incorrect
      incorporation opposite this nucleoside. Of the "translesion" Y-family human DNA
      polymerases (hpols), hpol eta is most efficient in incorporating equal numbers of
      correct and incorrect C and T bases. However, the mechanistic basis for this
      specific yet indiscriminate activity is not known. To explore this question, we
      report biochemical and structural analysis of the catalytic core of hpol eta.
      Activity assays showed the truncated form displayed similar misincorporation
      properties as the full-length enzyme, incorporating C and T equally and extending
      from both. X-ray crystal structures of both dC and dT paired with O6-MeG were
      solved in both insertion and extension modes. The structures revealed a Watson
      Crick-like pairing between O6-MeG and 2"-deoxythymidine-5"-[(alpha, beta)
      imido]triphosphate (approximating dT) at both the insertion and extension stages
      with formation of two H-bonds. Conversely, both the structures with O6- MeG
      opposite dCTP and dC display sheared configuration of base pairs but to different
      degrees, with formation of two bifurcated H-bonds and two single H-bonds in the
      structures trapped in the insertion and extension states, respectively. The
      structural data are consistent with the observed tendency of hpol eta to insert
      both dC and dT opposite the O6-MeG lesion with similar efficiencies. Comparison
      of the hpol eta active site configurations with either O6-MeG:dC or O6-MeG:dT
      bound compared with the corresponding situations in structures of complexes of
      Sulfolobus solfataricus Dpo4, a bypass pol that favors C relative to T by a
      factor of ~4, helps rationalize the more error-prone synthesis opposite the
      lesion by hpol eta.

PMID- 27694441
TI  - Electron Accepting Units of the Diheme Cytochrome c TsdA, a Bifunctional
      Thiosulfate Dehydrogenase/Tetrathionate Reductase.
AB  - The enzymes of the thiosulfate dehydrogenase (TsdA) family are wide-spread diheme
      c-type cytochromes. Here, redox carriers were studied mediating the flow of
      electrons arising from thiosulfate oxidation into respiratory or photosynthetic
      electron chains. In a number of organisms, including Thiomonas intermedia and
      Sideroxydans lithotrophicus, the tsdA gene is immediately preceded by tsdB
      encoding for another diheme cytochrome. Spectrophotometric experiments in
      combination with enzymatic assays in solution showed that TsdB acts as an
      effective electron acceptor of TsdA in vitro when TsdA and TsdB originate from
      the same source organism. Although TsdA covers a range from -300 to +150 mV, TsdB
      is redox active between -100 and +300 mV, thus enabling electron transfer between
      these hemoproteins. The three-dimensional structure of the TsdB-TsdA fusion
      protein from the purple sulfur bacterium Marichromatium purpuratum was solved by
      X-ray crystallography to 2.75 A resolution providing insights into internal
      electron transfer. In the oxidized state, this tetraheme cytochrome c contains
      three hemes with axial His/Met ligation, whereas heme 3 exhibits the His/Cys
      coordination typical for TsdA active sites. Interestingly, thiosulfate is
      covalently bound to Cys330 on heme 3. In several bacteria, including
      Allochromatium vinosum, TsdB is not present, precluding a general and essential
      role for electron flow. Both AvTsdA and the MpTsdBA fusion react efficiently in
      vitro with high potential iron-sulfur protein from A. vinosum (Em +350 mV). High
      potential iron-sulfur protein not only acts as direct electron donor to the
      reaction center in anoxygenic phototrophs but can also be involved in aerobic
      respiratory chains.

PMID- 27694440
TI  - Depletion of the Human Ion Channel TRPM2 in Neuroblastoma Demonstrates Its Key
      Role in Cell Survival through Modulation of Mitochondrial Reactive Oxygen Species
      and Bioenergetics.
AB  - Transient receptor potential melastatin 2 (TRPM2) ion channel has an essential
      function in modulating cell survival following oxidant injury and is highly
      expressed in many cancers including neuroblastoma. Here, in xenografts generated
      from neuroblastoma cells in which TRPM2 was depleted with CRISPR/Cas9 technology
      and in in vitro experiments, tumor growth was significantly inhibited and
      doxorubicin sensitivity increased. The hypoxia-inducible transcription factor
      1/2alpha (HIF-1/2alpha) signaling cascade including proteins involved in oxidant
      stress, glycolysis, and mitochondrial function was suppressed by TRPM2 depletion.
      TRPM2-depleted SH-SY5Y neuroblastoma cells demonstrated reduced oxygen
      consumption and ATP production after doxorubicin, confirming impaired cellular
      bioenergetics. In cells in which TRPM2 was depleted, mitochondrial superoxide
      production was significantly increased, particularly following doxorubicin.
      Ectopic expression of superoxide dismutase 2 (SOD2) reduced ROS and preserved
      viability of TRPM2-depleted cells, however, failed to restore ATP levels.
      Mitochondrial reactive oxygen species (ROS) were also significantly increased in
      cells in which TRPM2 function was inhibited by TRPM2-S, and pretreatment of these
      cells with the antioxidant MitoTEMPO significantly reduced ROS levels in response
      to doxorubicin and protected cell viability. Expression of the TRPM2 pore mutant
      E960D, in which calcium entry through TRPM2 is abolished, also resulted in
      significantly increased mitochondrial ROS following doxorubicin treatment,
      showing the critical role of TRPM2-mediated calcium entry. These findings
      demonstrate the important function of TRPM2 in modulation of cell survival
      through mitochondrial ROS, and the potential of targeted inhibition of TRPM2 as a
      therapeutic approach to reduce cellular bioenergetics, tumor growth, and enhance
      susceptibility to chemotherapeutic agents.

PMID- 27694442
TI  - Cell-specific Kaiso (ZBTB33) Regulation of Cell Cycle through Cyclin D1 and
      Cyclin E1.
AB  - The correlation between aberrant DNA methylation with cancer promotion and
      progression has prompted an interest in discerning the associated regulatory
      mechanisms. Kaiso (ZBTB33) is a specialized transcription factor that selectively
      recognizes methylated CpG-containing sites as well as a sequence-specific DNA
      target. Increasing reports link ZBTB33 overexpression and transcriptional
      activities with metastatic potential and poor prognosis in cancer, although there
      is little mechanistic insight into how cells harness ZBTB33 transcriptional
      capabilities to promote and progress disease. Here we report mechanistic details
      for how ZBTB33 mediates cell-specific cell cycle regulation. By utilizing ZBTB33
      depletion and overexpression studies, it was determined that in HeLa cells ZBTB33
      directly occupies the promoters of cyclin D1 and cyclin E1, inducing
      proliferation by promoting retinoblastoma phosphorylation and allowing for E2F
      transcriptional activity that accelerates G1- to S-phase transition. Conversely,
      in HEK293 cells ZBTB33 indirectly regulates cyclin E abundance resulting in
      reduced retinoblastoma phosphorylation, decreased E2F activity, and decelerated
      G1 transition. Thus, we identified a novel mechanism by which ZBTB33 mediates the
      cyclin D1/cyclin E1/RB1/E2F pathway, controlling passage through the G1
      restriction point and accelerating cancer cell proliferation.

PMID- 27694443
TI  - Balancing Selectivity and Efficacy of Bispecific Epidermal Growth Factor Receptor
      (EGFR) * c-MET Antibodies and Antibody-Drug Conjugates.
AB  - Bispecific antibodies (bsAbs) and antibody-drug conjugates (ADCs) have already
      demonstrated benefits for the treatment of cancer in several clinical studies,
      showing improved drug selectivity and efficacy. In particular, simultaneous
      targeting of prominent cancer antigens, such as EGF receptor (EGFR) and c-MET, by
      bsAbs has raised increasing interest for potentially circumventing receptor cross
      talk and c-MET-mediated acquired resistance during anti-EGFR monotherapy. In this
      study, we combined the selectivity of EGFR * c-MET bsAbs with the potency of
      cytotoxic agents via bispecific antibody-toxin conjugation. Affinity-attenuated
      bispecific EGFR * c-MET antibody-drug conjugates demonstrated high in vitro
      selectivity toward tumor cells overexpressing both antigens and potent anti-tumor
      efficacy. Due to basal EGFR expression in the skin, ADCs targeting EGFR in
      general warrant early safety assessments. Reduction in EGFR affinity led to
      decreased toxicity in keratinocytes. Thus, the combination of bsAb affinity
      engineering with the concept of toxin conjugation may be a viable route to
      improve the safety profile of ADCs targeting ubiquitously expressed antigens.

PMID- 27694444
TI  - Structural Dynamics of the Vimentin Coiled-coil Contact Regions Involved in
      Filament Assembly as Revealed by Hydrogen-Deuterium Exchange.
AB  - Intermediate filaments (IF) are major constituents of the cytoskeleton of
      metazoan cells. They are not only responsible for the mechanical properties but
      also for various physiological activities in different cells and tissues. The
      building blocks of IFs are extended coiled-coil-forming proteins exhibiting a
      characteristic central alpha-helical domain ("rod"). The fundamental principles
      of the filament assembly mechanism and the network formation have been widely
      elucidated for the cytoplasmic IF protein vimentin. Also, a comprehensive
      structural model for the tetrameric complex of vimentin has been obtained by X
      ray crystallography in combination with various biochemical and biophysical
      techniques. To extend these static data and to investigate the dynamic properties
      of the full-length proteins in solution during the various assembly steps, we
      analyzed the patterns of hydrogen-deuterium exchange in vimentin and in four
      variants carrying point mutations in the IF consensus motifs present at either
      end of the alpha-helical rod that cause an assembly arrest at the unit-length
      filament (ULF) stage. The results yielded unique insights into the structural
      properties of subdomains within the full-length vimentin, in particular in
      regions of contact in alpha-helical and linker segments that stabilize different
      oligomeric forms such as tetramers, ULFs, and mature filaments. Moreover,
      hydrogen-deuterium exchange analysis of the point-mutated variants directly
      demonstrated the active role of the IF consensus motifs in the oligomerization
      mechanism of tetramers during ULF formation. Ultimately, using molecular dynamics
      simulation procedures, we provide a structural model for the subdomain-mediated
      tetramer/tetramer interaction via "cross-coiling" as the first step of the
      assembly process.

PMID- 27694445
TI  - StarD7 Protein Deficiency Adversely Affects the Phosphatidylcholine Composition,
      Respiratory Activity, and Cristae Structure of Mitochondria.
AB  - Phosphatidylcholine (PC) is a major phospholipid of mitochondria, comprising 40
      50% of both the outer and the inner membranes. However, PC must be imported from
      its production organelles because mitochondria lack the enzymes essential for PC
      biosynthesis. In a previous study, we found that StarD7 mediates the
      intracellular transfer of PC to mitochondria. Therefore, in this study, we
      analyzed the contribution of StarD7 to the maintenance of mitochondrial
      phospholipid content and function using siRNA-mediated knockdown and knock-out
      (KO) of the StarD7 gene in HEPA-1 cells. Real time analysis of respiratory
      activity demonstrated that the oxygen consumption rate and activity of
      mitochondrial complexes were impaired in StarD7-KD cells. To confirm these
      results, we established StarD7-KO HEPA-1 cells by double nicking using
      CRISPR/Cas9n. As expected, StarD7-KD and -KO cells showed a significant reduction
      in mitochondrial PC content. The ATP level and growth rate of KO cells were
      notably lower compared with wild-type cells when cultured in glucose-free
      galactose-containing medium to force cells to rely on mitochondrial ATP
      production. In KO cells, the level of the MTCO1 protein, a primary subunit of
      complex IV, was reduced without a concomitant decrease in its mRNA, but the level
      was restored when StarD7-I was overexpressed. StarD7-KO cells showed impaired
      formation of the mitochondrial supercomplexes and exhibited a disorganized
      cristae structure, with no changes in optic atrophy 1 protein. These findings
      indicate that StarD7 plays important roles in maintaining the proper composition
      of mitochondrial phospholipids as well as mitochondrial function and
      morphogenesis.

PMID- 27694447
TI  - Glue sniffing.
AB  - Inhalant abuse refers to the inhalation of volatile substances for their euphoric
      effects. Glues and adhesives have been abused inhalants for decades and so the
      term "glue sniffing" attached to the habit. These days many substances used are
      not adhesives and the most accurate title of "solvent abuse" has been given to
      this widespread and dangerous habit. The various methods of inhalational abuse
      include huffing, bagging, dusting, glading, and sniffing. We report one such case
      of a 22-year-old male who was found in an unresponsive state at his residence
      with a plastic cover around his head and empty tubes of "Fevibond" glue beside
      him. He died on the way to hospital. At autopsy, conjunctival and visceral
      congestion were found with pulmonary edema and petechiae over visceral
      pericardium. The viscera were analyzed, and the presence of toluene in his liver
      and blood was reported.

PMID- 27694446
TI  - Crystal Structures of the Nuclear Receptor, Liver Receptor Homolog 1, Bound to
      Synthetic Agonists.
AB  - Liver receptor homolog 1 (NR5A2, LRH-1) is an orphan nuclear hormone receptor
      that regulates diverse biological processes, including metabolism, proliferation,
      and the resolution of endoplasmic reticulum stress. Although preclinical and
      cellular studies demonstrate that LRH-1 has great potential as a therapeutic
      target for metabolic diseases and cancer, development of LRH-1 modulators has
      been difficult. Recently, systematic modifications to one of the few known
      chemical scaffolds capable of activating LRH-1 failed to improve efficacy
      substantially. Moreover, mechanisms through which LRH-1 is activated by synthetic
      ligands are entirely unknown. Here, we use x-ray crystallography and other
      structural methods to explore conformational changes and receptor-ligand
      interactions associated with LRH-1 activation by a set of related agonists.
      Unlike phospholipid LRH-1 ligands, these agonists bind deep in the pocket and do
      not interact with residues near the mouth nor do they expand the pocket like
      phospholipids. Unexpectedly, two closely related agonists with similar efficacies
      (GSK8470 and RJW100) exhibit completely different binding modes. The dramatic
      repositioning is influenced by a differential ability to establish stable face-to
      face pi-pi-stacking with the LRH-1 residue His-390, as well as by a novel polar
      interaction mediated by the RJW100 hydroxyl group. The differing binding modes
      result in distinct mechanisms of action for the two agonists. Finally, we
      identify a network of conserved water molecules near the ligand-binding site that
      are important for activation by both agonists. This work reveals a previously
      unappreciated complexity associated with LRH-1 agonist development and offers
      insights into rational design strategies.

PMID- 27694449
TI  - Commentary on: Incidence and Risk Factors for Major Surgical Site Infections in
      Aesthetic Surgery: Analysis of 129,007 Patients.

PMID- 27694448
TI  - Five-Year Outcomes of Breast Augmentation with Form-Stable Implants: Periareolar
      vs Transaxillary.
AB  - BACKGROUND: Form-stable 410 implants have the potential advantage of maintaining
      their anatomic form thanks to the cohesiveness of the gel. Furthermore, Biocell
      texturing appears to maximize adhesion and to allow for implant immobility.
      OBJECTIVES: To compare the rate of reoperations for transaxillary and periareolar
      approaches for breast augmentation. METHODS: This retrospective study consisted
      of 373 patients with a 5-year follow up. Patient demographics, self-perception
      and esteem, surgical technique, and implant characteristics were documented. The
      reasons for reoperation for both approaches were reviewed. RESULTS: Transaxillary
      breast augmentation was used in 302 patients (81%) and periareolar breast
      augmentation in 71 patients (19%). In the axillary group, 210 had subfascial
      placement (69.5%), and 92 patients had submuscular placement (30.5%). In the
      nipple-areolar complex group, 50 were subfascial (70.4%), and 21 were submuscular
      (29.6%). The reoperation rate for the patients operated on during this time and
      followed for 5 years was 11% (8 patients) for the nipple-areolar complex approach
      and 8.3% (25 patients) in the axillary group. Capsular contracture grade III or
      IV were the main causes for reoperation for any technique (4.2% nipple-areolar
      complex vs 3.3% axillary). Other reasons were implant rupture, seroma, infection,
      implant malrotation, implant malposition, and rippling. CONCLUSIONS: The rate of
      reoperations was similar to those described in the literature for this type of
      implant. There were no statistically significant differences between the various
      techniques, although the reoperation rate was significantly higher when a
      periareolar subfascial technique was used. LEVEL OF EVIDENCE: 3 Therapeutic.

PMID- 27694450
TI  - Response to "Can We Really Control the Inframammary Fold (IMF) in Breast
      Augmentation?"

PMID- 27694452
TI  - Can We Really Control the Inframammary Fold (IMF) in Breast Augmentation?

PMID- 27694451
TI  - Incidence and Risk Factors for Major Surgical Site Infections in Aesthetic
      Surgery: Analysis of 129,007 Patients.
AB  - BACKGROUND: Surgical site infections (SSIs) represent one of the most common
      postoperative complications in patients undergoing aesthetic surgery. OBJECTIVES:
      This study reports the incidence and risk factors of major SSIs following
      aesthetic surgery. METHODS: A prospective cohort of patients who underwent
      aesthetic surgery between 2008 and 2013 was identified from the CosmetAssure
      database. Primary outcome was occurrence of a major SSI requiring emergency room
      visit, hospital admission, or reoperation within 30 days of the index operation.
      Univariate and multivariate analysis evaluated potential risk factors for SSIs
      including age, gender, body mass index (BMI), smoking, diabetes, type of surgical
      facility, procedure by body region, and combined procedures. RESULTS: A total of
      129,007 patients were identified, of which 599 (0.46%) had a major SSI. Mean age
      (43.8 +/- 12.4 years vs 40.9 +/- 13.9 years, P < .01) and BMI (27.3 +/- 5.5 kg/m2
      vs 24.3 +/- 4.6 kg/m2, P < .01) were higher in patients with SSIs. Patients with
      a SSI were more likely to be smokers (10.5% vs 8.2%, P = .04) and diabetic (4.5%
      vs 1.8%, P < .01). Females suffered more SSI than males (0.5% vs 0.3%, P = .02).
      Trunk/extremity procedures had a higher incidence of SSI compared to breast or
      face procedures (0.9% vs 0.2%, P < .01). On multivariate analysis, independent
      predictors of SSI included age (Relative Risk [RR] 1.01), female gender (RR
      1.86), BMI (RR 1.07), smoking (RR 1.61), diabetes (RR 1.58), hospital or
      ambulatory surgery center procedures (RR 1.39), trunk/extremity procedures (RR
      2.42), and combined procedures (RR 1.88). CONCLUSIONS: SSIs following cosmetic
      surgical procedures are associated with numerous independent predictors, which
      should be taken into consideration when counseling patients undergoing aesthetic
      surgery. LEVEL OF EVIDENCE: 2 Risk.

PMID- 27694453
TI  - Response to "Can We Really Control the Inframammary Fold (IMF) in Breast
      Augmentation?"

PMID- 27694454
TI  - Auto-Rim Flap Technique for Lateral Crura Caudal Excess Treatment.
AB  - BACKGROUND: There are many variables that influence nose tip harmony. Even in a
      rhinoplasty that appears successful in profile, one may see nostril asymmetries,
      alar retractions, or irregularities in the soft triangle, and patients express
      their dissatisfaction with these simple deformities. OBJECTIVES: In this study,
      we define the ratio of caudal and cephalic excess of the lower lateral cartilage.
      We evaluate whether it is possible to eliminate nostril asymmetries and alar
      retractions by means of supporting the facet polygon with the help of a lower
      lateral cartilage auto-rim flap, a technique we have developed in our
      rhinoplasties. METHODS: The auto-rim flap was used successively on 498 primary
      rhinoplasty patients on whom the same surgeon operated between May 2013 and June
      2015, performing marginal incisions. RESULTS: Of the 498 patients in the series,
      only 1 of the first 10 required a revision due to tip asymmetry related to the
      auto-rim flap. A minimal nostril asymmetry that did not require intervention
      occurred in 10 patients. In none of the patients could an increased alar
      retraction be seen postoperatively. All patients exhibited alar cartilage in the
      anatomically correct position. CONCLUSIONS: With the auto-rim flap technique, a
      part of the caudal excess of the alar cartilage remains as a flap in the facet
      region; therefore, there is no need in the cephalic region to perform more of an
      excision than what is strictly necessary. LEVEL OF EVIDENCE: 4 Therapeutic.

PMID- 27694455
TI  - Commentary on: Lower Eyelid Retraction Surgery Without Internal Spacer Graft.

PMID- 27694456
TI  - Why Should We All Be Cultural Psychologists? Lessons From the Study of Social
      Cognition.
AB  - I call the attention of psychologists to the pivotal role of cultural psychology
      in extending and enriching research programs. I argue that it is not enough to
      simply acknowledge the importance of culture and urge psychologists to practice
      cultural psychology in their research. I deconstruct five assumptions about
      cultural psychology that seriously undermine its contribution to the building of
      a true psychological science, including that cultural psychology (a) is only
      about finding group differences, (b) does not appertain to group similarities,
      (c) concerns only group-level analysis, (d) is irrelevant to basic psychological
      processes, and (e) is used only to confirm the generalizability of theories. I
      discuss how cultural psychology can provide unique insights into psychological
      processes and further equip researchers with additional tools to understand human
      behavior. Drawing lessons from the 20 years of cultural research that my
      colleagues and I have done on the development of social cognition, including
      autobiographical memory, future thinking, self, and emotion knowledge, I
      demonstrate that incorporating cultural psychology into research programs is not
      only necessary but also feasible.

PMID- 27694458
TI  - Psychogenic Explanations of Physical Illness: Time to Examine the Evidence.
AB  - In some patients with chronic physical complaints, detailed examination fails to
      reveal a well-recognized underlying disease process. In this situation, the
      physician may suspect a psychological cause. In this review, we critically
      evaluated the evidence for this causal claim, focusing on complaints presenting
      as neurological disorders. There were four main conclusions. First, patients with
      these complaints frequently exhibit psychopathology but not consistently more
      often than patients with a comparable "organic" diagnosis, so a causal role
      cannot be inferred. Second, these patients report a high incidence of adverse
      life experiences, but again, there is insufficient evidence to indicate a causal
      role for any particular type of experience. Third, although psychogenic illnesses
      are believed to be more responsive to psychological interventions than comparable
      "organic" illnesses, there is currently no evidence to support this claim.
      Finally, recent evidence suggests that biological and physical factors play a
      much greater causal role in these illnesses than previously believed. We conclude
      that there is currently little evidential support for psychogenic theories of
      illness in the neurological domain. In future research, researchers need to take
      a wider view concerning the etiology of these illnesses.

PMID- 27694457
TI  - A Complex Network Perspective on Clinical Science.
AB  - Contemporary classification systems for mental disorders assume that abnormal
      behaviors are expressions of latent disease entities. An alternative to the
      latent disease model is the complex network approach. Instead of assuming that
      symptoms arise from an underlying disease entity, the complex network approach
      holds that disorders exist as systems of interrelated elements of a network. This
      approach also provides a framework for the understanding of therapeutic change.
      Depending on the structure of the network, change can occur abruptly once the
      network reaches a critical threshold (the tipping point). Homogeneous and highly
      connected networks often recover more slowly from local perturbations when the
      network approaches the tipping point, potentially making it possible to predict
      treatment change, relapse, and recovery. In this article, we discuss the complex
      network approach as an alternative to the latent disease model and its
      implications for classification, therapy, relapse, and recovery.

PMID- 27694460
TI  - Introduction to Optimizing Learning in College: Tips From Cognitive Psychology.

PMID- 27694459
TI  - Social Climate Science: A New Vista for Psychological Science.
AB  - The recent Paris Agreement to limit greenhouse gas emissions, adopted by 195
      nations at the 2015 United Nations Climate Change Conference, signaled
      unprecedented commitment by world leaders to address the human social aspects of
      climate change. Indeed, climate change increasingly is recognized by scientists
      and policymakers as a social issue requiring social solutions. However, whereas
      psychological research on intrapersonal and some group-level processes (e.g.,
      political polarization of climate beliefs) has flourished, research into other
      social processes-such as an understanding of how nonpartisan social identities,
      cultural ideologies, and group hierarchies shape public engagement on climate
      change-has received substantially less attention. In this article, we take stock
      of current psychological approaches to the study of climate change to explore
      what is "social" about climate change from the perspective of psychology. Drawing
      from current interdisciplinary perspectives and emerging empirical findings
      within psychology, we identify four distinct features of climate change and three
      sets of psychological processes evoked by these features that are fundamentally
      social and shape both individual and group responses to climate change. Finally,
      we consider how a more nuanced understanding of the social underpinnings of
      climate change can stimulate new questions and advance theory within psychology.

PMID- 27694461
TI  - Optimizing Learning in College: Tips From Cognitive Psychology.
AB  - Every fall, thousands of college students begin their first college courses,
      often in large lecture settings. Many students, even those who work hard,
      flounder. What should students be doing differently? Drawing on research in
      cognitive psychology and our experience as educators, we provide suggestions
      about how students should approach taking a course in college. We discuss time
      management techniques, identify the ineffective study strategies students often
      use, and suggest more effective strategies based on research in the lab and the
      classroom. In particular, we advise students to space their study sessions on a
      topic and to quiz themselves, as well as using other active learning strategies
      while reading. Our goal was to provide a framework for students to succeed in
      college classes.

PMID- 27694462
TI  - Introduction to the Special Section on Improving Research Practices: Thinking
      Deeply Across the Research Cycle.

PMID- 27694463
TI  - Optimizing Research Payoff.
AB  - In this article, we present a model for determining how total research payoff
      depends on researchers' choices of sample sizes, alpha levels, and other
      parameters of the research process. The model can be used to quantify various
      trade-offs inherent in the research process and thus to balance competing goals,
      such as (a) maximizing both the number of studies carried out and also the
      statistical power of each study, (b) minimizing the rates of both false positive
      and false negative findings, and (c) maximizing both replicability and research
      efficiency. Given certain necessary information about a research area, the model
      can be used to determine the optimal values of sample size, statistical power,
      rate of false positives, rate of false negatives, and replicability, such that
      overall research payoff is maximized. More specifically, the model shows how the
      optimal values of these quantities depend upon the size and frequency of true
      effects within the area, as well as the individual payoffs associated with
      particular study outcomes. The model is particularly relevant within current
      discussions of how to optimize the productivity of scientific research, because
      it shows which aspects of a research area must be considered and how these
      aspects combine to determine total research payoff.

PMID- 27694464
TI  - Graphical Descriptives: A Way to Improve Data Transparency and Methodological
      Rigor in Psychology.
AB  - Several calls have recently been issued to the social sciences for enhanced
      transparency of research processes and enhanced rigor in the methodological
      treatment of data and data analytics. We propose the use of graphical
      descriptives (GDs) as one mechanism for responding to both of these calls. GDs
      provide a way to visually examine data. They serve as quick and efficient tools
      for checking data distributions, variable relations, and the potential
      appropriateness of different statistical analyses (e.g., do data meet the minimum
      assumptions for a particular analytic method). Consequently, we believe that GDs
      can promote increased transparency in the journal review process, encourage best
      practices for data analysis, and promote a more inductive approach to
      understanding psychological data. We illustrate the value of potentially
      including GDs as a step in the peer-review process and provide a user-friendly
      online resource (www.graphicaldescriptives.org) for researchers interested in
      including data visualizations in their research. We conclude with suggestions on
      how GDs can be expanded and developed to enhance transparency.

PMID- 27694465
TI  - Increasing Transparency Through a Multiverse Analysis.
AB  - Empirical research inevitably includes constructing a data set by processing raw
      data into a form ready for statistical analysis. Data processing often involves
      choices among several reasonable options for excluding, transforming, and coding
      data. We suggest that instead of performing only one analysis, researchers could
      perform a multiverse analysis, which involves performing all analyses across the
      whole set of alternatively processed data sets corresponding to a large set of
      reasonable scenarios. Using an example focusing on the effect of fertility on
      religiosity and political attitudes, we show that analyzing a single data set can
      be misleading and propose a multiverse analysis as an alternative practice. A
      multiverse analysis offers an idea of how much the conclusions change because of
      arbitrary choices in data construction and gives pointers as to which choices are
      most consequential in the fragility of the result.

PMID- 27694466
TI  - Conducting Meta-Analyses Based on p Values: Reservations and Recommendations for
      Applying p-Uniform and p-Curve.
AB  - Because of overwhelming evidence of publication bias in psychology, techniques to
      correct meta-analytic estimates for such bias are greatly needed. The methodology
      on which the p-uniform and p-curve methods are based has great promise for
      providing accurate meta-analytic estimates in the presence of publication bias.
      However, in this article, we show that in some situations, p-curve behaves
      erratically, whereas p-uniform may yield implausible estimates of negative effect
      size. Moreover, we show that (and explain why) p-curve and p-uniform result in
      overestimation of effect size under moderate-to-large heterogeneity and may yield
      unpredictable bias when researchers employ p-hacking. We offer hands-on
      recommendations on applying and interpreting results of meta-analyses in general
      and p-uniform and p-curve in particular. Both methods as well as traditional
      methods are applied to a meta-analysis on the effect of weight on judgments of
      importance. We offer guidance for applying p-uniform or p-curve using R and a
      user-friendly web application for applying p-uniform.

PMID- 27694467
TI  - Adjusting for Publication Bias in Meta-Analysis: An Evaluation of Selection
      Methods and Some Cautionary Notes.
AB  - We review and evaluate selection methods, a prominent class of techniques first
      proposed by Hedges (1984) that assess and adjust for publication bias in meta
      analysis, via an extensive simulation study. Our simulation covers both
      restrictive settings as well as more realistic settings and proceeds across
      multiple metrics that assess different aspects of model performance. This
      evaluation is timely in light of two recently proposed approaches, the so-called
      p-curve and p-uniform approaches, that can be viewed as alternative
      implementations of the original Hedges selection method approach. We find that
      the p-curve and p-uniform approaches perform reasonably well but not as well as
      the original Hedges approach in the restrictive setting for which all three were
      designed. We also find they perform poorly in more realistic settings, whereas
      variants of the Hedges approach perform well. We conclude by urging caution in
      the application of selection methods: Given the idealistic model assumptions
      underlying selection methods and the sensitivity of population average effect
      size estimates to them, we advocate that selection methods should be used less
      for obtaining a single estimate that purports to adjust for publication bias ex
      post and more for sensitivity analysis-that is, exploring the range of estimates
      that result from assuming different forms of and severity of publication bias.

PMID- 27694469
TI  - Reflections on the Commitment-Forgiveness Registered Replication Report.

PMID- 27694468
TI  - Registered Replication Report: Study 1 From Finkel, Rusbult, Kumashiro, & Hannon
      (2002).
AB  - Finkel, Rusbult, Kumashiro, and Hannon (2002, Study 1) demonstrated a causal link
      between subjective commitment to a relationship and how people responded to
      hypothetical betrayals of that relationship. Participants primed to think about
      their commitment to their partner (high commitment) reacted to the betrayals with
      reduced exit and neglect responses relative to those primed to think about their
      independence from their partner (low commitment). The priming manipulation did
      not affect constructive voice and loyalty responses. Although other studies have
      demonstrated a correlation between subjective commitment and responses to
      betrayal, this study provides the only experimental evidence that inducing
      changes to subjective commitment can causally affect forgiveness responses. This
      Registered Replication Report (RRR) meta-analytically combines the results of 16
      new direct replications of the original study, all of which followed a
      standardized, vetted, and preregistered protocol. The results showed little
      effect of the priming manipulation on the forgiveness outcome measures, but it
      also did not observe an effect of priming on subjective commitment, so the
      manipulation did not work as it had in the original study. We discuss possible
      explanations for the discrepancy between the findings from this RRR and the
      original study.

PMID- 27694470
TI  - The conundrum of malaria chemoprophylaxis.
AB  - Alternative approaches to malaria chemoprophylaxis are discussed in light of the
      difficulties of executing clinical trials within limits of infection rates and
      ethics.

PMID- 27694471
TI  - IL-17A-mediated expression of epithelial IL-17C promotes inflammation during
      acute Pseudomonas aeruginosa pneumonia.
AB  - Lung epithelial cells are suggested to promote pathogen-induced pulmonary
      inflammation by the release of chemokines, resulting in enhanced recruitment of
      circulating leukocytes. Recent studies have shown that the interleukin-17C (IL
      17C) regulates innate immune functions of epithelial cells in an autocrine
      manner. The aim of this study was to investigate the contribution of IL-17C to
      pulmonary inflammation in a mouse model of acute Pseudomonas aeruginosa
      pneumonia. Infection with P. aeruginosa resulted in an increased expression of IL
      17C in lung tissue of wild-type mice. Numbers of neutrophils and the expression
      of the neutrophil-recruiting chemokines keratinocyte-derived chemokine and
      macrophage inflammatory protein 2 were significantly decreased in lungs of IL-17C
      deficient (IL-17C-/-) mice infected with P. aeruginosa at 24 h. Systemic
      concentrations of interleukin-6 (IL-6) were significantly decreased in infected
      IL-17C-/- mice at 24 h and the survival of IL-17C-/- mice was significantly
      increased at 48 h. The expression of IL-17C was reduced in infected mice
      deficient for interleukin-17A (IL-17A), whereas pulmonary concentrations of IL
      17A were not affected by the deficiency for IL-17C. Stimulation of primary
      alveolar epithelial cells with IL-17A resulted in a significantly increased
      expression of IL-17C in vitro. Our data suggest that IL-17A-mediated expression
      of epithelial IL-17C amplifies the release of chemokines by epithelial cells and
      thereby contributes to the recruitment of neutrophils and systemic inflammation
      during acute P. aeruginosa pneumonia.

PMID- 27694473
TI  - Simvastatin prevents and reverses chronic pulmonary hypertension in newborn rats
      via pleiotropic inhibition of RhoA signaling.
AB  - Chronic neonatal pulmonary hypertension (PHT) frequently results in early death.
      Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse
      chronic PHT in neonatal rats, but at the cost of severe adverse effects,
      including systemic hypotension and growth restriction. Simvastatin has
      pleiotropic inhibitory effects on isoprenoid intermediates that may limit
      activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that
      statin treatment would safely limit pulmonary vascular RhoA activity and prevent
      and reverse experimental chronic neonatal PHT via downstream inhibitory effects
      on pathological ROCK activity. Sprague-Dawley rats in normoxia (room air) or
      moderate normobaric hypoxia (13% O2) received simvastatin (2 mg.kg-1.day-1 ip) or
      vehicle from postnatal days 1-14 (prevention protocol) or from days 14-21 (rescue
      protocol). Chronic hypoxia increased RhoA and ROCK activity in lung tissue.
      Simvastatin reduced lung content of the isoprenoid intermediate farnesyl
      pyrophosphate and decreased RhoA/ROCK signaling in the hypoxia-exposed lung.
      Preventive or rescue treatment of chronic hypoxia-exposed animals with
      simvastatin decreased pulmonary vascular resistance, right ventricular
      hypertrophy, and pulmonary arterial remodeling. Preventive simvastatin treatment
      improved weight gain, did not lower systemic blood pressure, and did not cause
      apparent toxic effects on skeletal muscle, liver or brain. Rescue therapy with
      simvastatin improved exercise capacity. We conclude that simvastatin limits
      RhoA/ROCK activity in the chronic hypoxia-exposed lung, thus preventing or
      ameliorating hemodynamic and structural markers of chronic PHT and improving long
      term outcome, without causing adverse effects.

PMID- 27694474
TI  - Of mice and men: correlations between microRNA-17~92 cluster expression and
      promoter methylation in severe bronchopulmonary dysplasia.
AB  - We previously demonstrated that decreased miR-17~92 cluster expression was 1)
      present in lungs from human infants who died with bronchopulmonary dysplasia
      (BPD); 2) inversely correlated with DNA methyltransferase (DNMT) expression and
      promoter methylation; and 3) correlated with a subsequent diagnosis of BPD at 36
      wk gestational age. We tested the hypothesis that plasma miR-17 levels would be
      lowest in infants who ultimately develop severe BPD. Secondly, we utilized our
      well-characterized murine model of severe BPD that combines perinatal
      inflammation with postnatal hyperoxia to test the hypothesis that alterations in
      lung miR-17~92, DNMT, and promoter methylation in our model would mirror our
      findings in tissues from premature human infants. Plasma was obtained during the
      first 5 days of life from premature infants born <=32 wk gestation. Lung tissues
      were harvested from mice exposed to maternal inflammation and neonatal hyperoxia
      for 14 days after birth. miR-17~92 cluster expression and DNA methyltransferase
      expression were measured by qRT-PCR, and promoter methylation was assessed by
      Methyl-Profiler assay. Plasma miR-17 levels are significantly lower in the first
      week of life in human infants who develop severe BPD compared with mild or
      moderate BPD. Data from our severe BPD murine model reveal that lung miR-17~92
      cluster expression is significantly attenuated, and levels inversely correlated
      with DNMT expression and miR-17~92 cluster promoter methylation. Collectively,
      our data support a plausible role for epigenetically altered miR-17~92 cluster in
      the pathogenesis of severe BPD.

PMID- 27694472
TI  - Neutrophils promote alveolar epithelial regeneration by enhancing type II
      pneumocyte proliferation in a model of acid-induced acute lung injury.
AB  - Alveolar epithelial regeneration is essential for resolution of the acute
      respiratory distress syndrome (ARDS). Although neutrophils have traditionally
      been considered mediators of epithelial damage, recent studies suggest they
      promote type II pneumocyte (AT2) proliferation, which is essential for
      regenerating alveolar epithelium. These studies did not, however, evaluate this
      relationship in an in vivo model of alveolar epithelial repair following injury.
      To determine whether neutrophils influence alveolar epithelial repair in vivo, we
      developed a unilateral acid injury model that creates a severe yet survivable
      injury with features similar to ARDS. Mice that received injections of the
      neutrophil-depleting Ly6G antibody had impaired AT2 proliferation 24 and 72 h
      after acid instillation, which was associated with decreased reepithelialization
      and increased alveolar protein concentration 72 h after injury. As neutrophil
      depletion itself may alter the cytokine response, we questioned the contribution
      of neutrophils to alveolar epithelial repair in neutropenic granulocyte-colony
      stimulating factor (G-CSF)-/- mice. We found that the loss of G-CSF recapitulated
      the neutrophil response of Ly6G-treated mice and was associated with defective
      alveolar epithelial repair, similar to neutrophil-depleted mice, and was reversed
      by administration of exogenous G-CSF. To approach the mechanisms, we employed an
      unbiased protein analysis of bronchoalveolar lavage fluid from neutrophil
      depleted and neutrophil-replete mice 12 h after inducing lung injury. Pathway
      analysis identified significant differences in multiple signaling pathways that
      may explain the differences in epithelial repair. These data emphasize an
      important link between the innate immune response and tissue repair in which
      neutrophils promote alveolar epithelial regeneration.

PMID- 27694475
TI  - Attenuated heme oxygenase-1 responses predispose the elderly to pulmonary
      nontuberculous mycobacterial infections.
AB  - Pulmonary infections with nontuberculous mycobacteria (P-NTM), such as by
      Mycobacterium avium complex (M. avium), are increasingly found in the elderly,
      but the underlying mechanisms are unclear. Recent studies suggest that adaptive
      immunity is necessary, but not sufficient, for host defense against mycobacteria.
      Heme oxygenase-1 (HO-1) has been recognized as a critical modulator of granuloma
      formation and programmed cell death in mycobacterial infections. Old mice (18-21
      mo) infected with M. avium had attenuated HO-1 response with diffuse
      inflammation, high burden of mycobacteria, poor granuloma formation, and
      decreased survival (45%), while young mice (4-6 mo) showed tight, well-defined
      granuloma, increased HO-1 expression, and increased survival (95%). To further
      test the role of HO-1 in increased susceptibility to P-NTM infections in the
      elderly, we used old and young HO-1+/+ and HO-1-/- mice. The transcriptional
      modulation of the JAK/STAT signaling pathway in HO-1-/- mice due to M. avium
      infection demonstrated similarities to infected wild-type old mice with
      upregulation of SOCS3 and inhibition of Bcl2. Higher expression of SOCS3 with
      downregulation of Bcl2 resulted in higher macrophage death via cellular necrosis.
      Finally, peripheral blood monocytes (PBMCs) from elderly patients with P-NTM also
      demonstrated attenuated HO-1 responses after M. avium stimulation and increased
      cell death due to cellular necrosis (9.69% +/- 2.02) compared with apoptosis
      (4.75% +/- 0.98). The augmented risk for P-NTM in the elderly is due, in part, to
      attenuated HO-1 responses, subsequent upregulation of SOCS3, and inhibition of
      Bcl2, leading to programmed cell death of macrophages, and sustained infection.

PMID- 27694477
TI  - Ten years too long: strontium ranelate, cardiac events, and the European
      Medicines Agency.

PMID- 27694476
TI  - Genomic Survey of a Hyperparasitic Microsporidian Amphiamblys sp.
      (Metchnikovellidae).
AB  - Metchnikovellidae are a group of unusual microsporidians that lack some of the
      defining ultrastructural features characteristic of derived Microsporidia and are
      thought to be one of their earliest-branching lineages. The basal position of
      metchnikovellids was never confirmed by molecular phylogeny in published
      research, and thus far no genomic data for this group were available. In this
      work, we obtain a partial genome of metchnikovellid Amphiamblys sp. using
      multiple displacement amplification, next-generation sequencing, and metagenomic
      binning approaches. The partial genome, which we estimate to be close to 90%
      complete, displays genome compaction on par with gene-dense microsporidian
      genomes, but contains an unusual repertoire of unique repeat elements.
      Phylogenetic analyses of multigene datasets place Amphiamblys sp. as the first
      branch of the microsporidian lineage following the divergence of a mitochondriate
      microsporidian Mitosporidium. We find evidence for a mitochondrial remnant
      presumably functionally equivalent to a mitosome in Amphiamblys sp. and the
      common enzymatic complement for microsporidian anaerobic metabolism. Comparative
      genomic analyses identify the conservation of components for clathrin vesicle
      formation as one of the key features distinguishing the metchnikovellid from its
      highly derived relatives. The presented data confirm the notion of
      Metchnikovellidae as a less derived microsporidian group, and provide an
      additional stepping stone for reconstruction of an evolutionary transition from
      the early diverging parasitic fungi to derived Microsporidia.

PMID- 27694479
TI  - Coinfection With Zika and Dengue-2 Viruses in a Traveler Returning From Haiti,
      2016: Clinical Presentation and Genetic Analysis.
AB  - Zika virus and dengue virus serotype 2 were isolated from a patient with travel
      to Haiti who developed fever, rash, arthralgias, and conjunctivitis. The
      infecting Zika virus was related to Venezuelan and Brazilian strains but evolved
      along a lineage originating from strains isolated in 2014 in the same region of
      Haiti.

PMID- 27694478
TI  - Role of FEN1 S187 phosphorylation in counteracting oxygen-induced stress and
      regulating postnatal heart development.
AB  - Flap endonuclease 1 (FEN1) phosphorylation is proposed to regulate the action of
      FEN1 in DNA repair as well as Okazaki fragment maturation. However, the biologic
      significance of FEN1 phosphorylation in response to DNA damage remains unknown.
      Here, we report an in vivo role for FEN1 phosphorylation, using a mouse line
      carrying S187A FEN1, which abolishes FEN1 phosphorylation. Although S187A mouse
      embryonic fibroblast cells showed normal proliferation under low oxygen levels
      (2%), the mutant cells accumulated oxidative DNA damage, activated DNA damage
      checkpoints, and showed G1-phase arrest at atmospheric oxygen levels (21%). This
      suggests an essential role for FEN1 phosphorylation in repairing oxygen-induced
      DNA damage and maintaining proper cell cycle progression. Consistently, the
      mutant cardiomyocytes showed G1-phase arrest due to activation of the p53
      mediated DNA damage response at the neonatal stage, which reduces the
      proliferation potential of the cardiomyocytes and impairs heart development.
      Nearly 50% of newborns with the S187A mutant died in the first week due to
      failure to undergo the peroxisome proliferator-activated receptor signaling
      dependent switch from glycolysis to fatty acid oxidation. The adult mutant mice
      developed dilated hearts and showed significantly shorter life spans. Altogether,
      our results reveal an important role of FEN1 phosphorylation to counteract oxygen
      induced stress in the heart during the fetal-to-neonatal transition.-Zhou, L.,
      Dai, H., Wu, J., Zhou, M., Yuan, H., Du, J., Yang, L., Wu, X., Xu, H., Hua, Y.,
      Xu, J., Zheng, L., Shen, B. Role of FEN1 S187 phosphorylation in counteracting
      oxygen-induced stress and regulating postnatal heart development.

PMID- 27694480
TI  - Cervicovaginal Inflammation Facilitates Acquisition of Less Infectious HIV
      Variants.
AB  - We evaluated whether genital inflammation affects the selection of the
      transmitted virus. Among South African women, we found that preinfection genital
      inflammation facilitates transmission of less infectious human immunodeficiency
      virus, but highly infectious viruses are able to establish infection regardless
      of inflammation status. This suggests that viral phenotype can influence
      transmission risk.

PMID- 27694481
TI  - Antiretroviral Therapy to Prevent HIV Acquisition: Limits of Estimation From a
      Population Cohort.

PMID- 27694482
TI  - Reply to Cohen et al.

PMID- 27694483
TI  - Antibiotic Use in Small Community Hospitals.
AB  - BACKGROUND:  Antibiotic use and misuse is driving drug resistance. Much of US
      healthcare takes place in small community hospitals (SCHs); 70% of all US
      hospitals have <200 beds. Antibiotic use in SCHs is poorly described. We
      evaluated antibiotic use using data from the National Healthcare and Safety
      Network antimicrobial use option from the Centers for Disease Control and
      Prevention. METHODS:  We used Intermountain Healthcare's monthly antibiotic use
      reports for 19 hospitals from 2011 to 2013. Hospital care units were categorized
      as intensive care, medical/surgical, pediatric, or miscellaneous. Antibiotics
      were categorized based on spectrum of coverage. Antibiotic use rates, expressed
      as days of therapy per 1000 patient-days (DOT/1000PD), were calculated for each
      SCH and compared with rates in large community hospitals (LCHs). Negative
      binomial regression was used to relate antibiotic use to predictor variables.
      RESULTS:  Total antibiotic use rates varied widely across the 15 SCHs (median,
      436 DOT/1000PD; range, 134-671 DOT/1000PD) and were similar to rates in 4 LCHs
      (509 DOT/1000PD; 406-597 DOT/1000PD). The proportion of patient-days spent in the
      respective unit types varied substantially within SCHs and had a large impact on
      facility-level rates. Broad-spectrum antibiotics accounted for 26% of use in SCHs
      (range, 8%-36%), similar to the proportion in LCHs (32%; range, 26%-37%). Case
      mix index, proportion of patient-days in specific unit types, and season were
      significant predictors of antibiotic use. CONCLUSIONS:  There is substantial
      variation in patterns of antibiotic use among SCHs. Overall usage in SCHs is
      similar to usage in LCHs. Small hospitals need to become a focus of stewardship
      efforts.

PMID- 27694484
TI  - Patient-reported outcome measure for neuromyelitis optica: pretesting of
      preliminary instrument and protocol for further development in accordance with
      international guidelines.
AB  - OBJECTIVE: This study outlines the development of a patient-reported outcome
      measure (PROM), an instrument to obtain self-reported health status for
      neuromyeltis optica (NMO), a disabling neurological condition. DESIGN:
      Development was conducted in accordance with international guidance for PROMs
      including systematic review of existing literature, item generation guided by
      qualitative interviews, health-related quality of life conceptual framework and
      clinical expert panel and cognitive interviews with NMO patients. SETTING:
      Participants were identified through a national NMO clinic in a tertiary NHS
      neurosciences service. PARTICIPANTS: 15 individuals with NMO participated in
      cognitive interviews requiring review and ranking of proposed PROM items and
      qualitative feedback on content, layout and response options. RESULTS:
      Participants endorsed the draft instrument as reflecting their experience of the
      condition and as being easy to understand. Rating and ranking of item relevance
      and importance reduced the draft instrument from 106 to 48 items. Participant
      feedback on overlapping items eliminated a further 2 items and resulted in a
      preliminary instrument of 46 items. As a direct result of participant feedback
      ordering of the 10 domains was revised, a 4 option Likert scale was employed and
      a 4-week recall period for impact of symptoms was selected. CONCLUSIONS: A 46
      item instrument developed in accordance with international PROM development
      guidelines through literature review, developed by subject matter experts and
      refined through pretesting examining content validity provides a preliminary
      measure for assessing patient-report of health status in NMO. Further evaluation
      is proposed including sensitivity to clinical change, and international
      contributions to evaluating the measure are encouraged.

PMID- 27694485
TI  - Effectiveness of the 'Back-to-Sleep' campaigns among healthcare professionals in
      the past 20 years: a systematic review.
AB  - OBJECTIVES: From the late 1980s 'Back-to-Sleep' (BTS) campaigns were run in most
      developed countries to increase awareness of the supine position's protective
      effect against sleep-related infant deaths. Once the media awareness-raising
      action associated with these campaigns ended, healthcare professionals' role
      became crucial. The goal of this paper is to determine if healthcare
      professionals' knowledge and parent advice consistent with evidence-based infant
      sleep recommendations have changed over the past 20 years. SETTING: All studies
      investigating healthcare professionals' knowledge and/or advice to parents were
      included in a systematic review. The search was performed in PubMed and in
      MEDLINE, and 21 studies were identified. RESULTS: The correctness of healthcare
      professionals' knowledge and parent advice about the supine sleeping position
      increased over the past 20 years. However, the percentage of those aware that
      parents should avoid putting their babies to sleep in a prone position is
      decreasing over time: from about 97% in the 1990s to about 90% at the end of the
      2000s. CONCLUSIONS: The effectiveness of the BTS campaigns in publicising the
      benefits of the supine position is confirmed by this paper. More and more
      healthcare professionals know that it is the best position to reduce the risk of
      sleep-related deaths and they recommend it exclusively. However, the decrease in
      the knowledge about non-prone positions suggests that the campaigns may not have
      focused enough on the dangers of the prone position.

PMID- 27694486
TI  - Implementing the RISE second victim support programme at the Johns Hopkins
      Hospital: a case study.
AB  - BACKGROUND: Second victims are healthcare workers who experience emotional
      distress following patient adverse events. Studies indicate the need to develop
      organisational support programmes for these workers. The RISE (Resilience In
      Stressful Events) programme was developed at the Johns Hopkins Hospital to
      provide this support. OBJECTIVE: To describe the development of RISE and evaluate
      its initial feasibility and subsequent implementation. Programme phases included
      (1) developing the RISE programme, (2) recruiting and training peer responders,
      (3) pilot launch in the Department of Paediatrics and (4) hospital-wide
      implementation. METHODS: Mixed-methods study, including frequency counts of
      encounters, staff surveys and evaluations by RISE peer responders. Descriptive
      statistics were used to summarise demographic characteristics and proportions of
      responses to categorical, Likert and ordinal scales. Qualitative analysis and
      coding were used to analyse open-ended responses from questionnaires and focus
      groups. RESULTS: A baseline staff survey found that most staff had experienced an
      unanticipated adverse event, and most would prefer peer support. A total of 119
      calls, involving ~500 individuals, were received in the first 52 months. The
      majority of calls were from nurses, and very few were related to medical errors
      (4%). Peer responders reported that the encounters were successful in 88% of
      cases and 83.3% reported meeting the caller's needs. Low awareness of the
      programme was a barrier to hospital-wide expansion. However, over the 4 years,
      the rate of calls increased from ~1-4 calls per month. The programme evolved to
      accommodate requests for group support. CONCLUSIONS: Hospital staff identified
      the need for a multidisciplinary peer support programme for second victims. Peer
      responders reported success in responding to calls, the majority of which were
      for adverse events rather than for medical errors. The low initial volume of
      calls emphasises the importance of promoting awareness of the value of emotional
      support and the availability of the programme.

PMID- 27694487
TI  - Association of neck circumference with general and abdominal obesity in children
      and adolescents: the weight disorders survey of the CASPIAN-IV study.
AB  - OBJECTIVES: This study aimed to evaluate the association of neck circumference
      (NC) with obesity to determine the sex-specific and age-specific optimal cut-off
      points of this measure in association with obesity in a national sample of the
      Iranian paediatric population. METHODS: This survey on weight disorders was
      conducted among a national sample of Iranian children and adolescents, aged 6-18
      years. Using the area under the curve (AUC) of the receiver operator
      characteristic curves, we evaluated the association of NC with general and
      abdominal obesity. RESULTS: This national survey was conducted among 23 043
      school students (50.8% boys) with a mean age (SD) of 12.55 (3.31) years. A
      significant association was documented between NC and other anthropometric
      measures in both sexes and in the whole population. In all age groups and
      genders, NC performed relatively well in classifying participants to overweight
      (AUC: 0.67 to 0.75, p<0.001), general obesity (AUC: 0.81 to 0.85, p<0.001) and
      abdominal obesity (AUC: 0.73 to 0.78, p<0.001). CONCLUSIONS: NC can be considered
      as a simple time-saving clinical tool for obesity detection in large population
      based studies in children and adolescents. It is significantly correlated with
      indices of adiposity and can reliably identify children with general and
      abdominal obesity in the Iranian paediatric population.

PMID- 27694488
TI  - Identification and outcomes of clinical phenotypes in amyotrophic lateral
      sclerosis/motor neuron disease: Australian National Motor Neuron Disease
      observational cohort.
AB  - OBJECTIVE: To capture the clinical patterns, timing of key milestones and
      survival of patients presenting with amyotrophic lateral sclerosis/motor neuron
      disease (ALS/MND) within Australia. METHODS: Data were prospectively collected
      and were timed to normal clinical assessments. An initial registration clinical
      report form (CRF) and subsequent ongoing assessment CRFs were submitted with a
      completion CRF at the time of death. DESIGN: Prospective observational cohort
      study. PARTICIPANTS: 1834 patients with a diagnosis of ALS/MND were registered
      and followed in ALS/MND clinics between 2005 and 2015. RESULTS: 5 major clinical
      phenotypes were determined and included ALS bulbar onset, ALS cervical onset and
      ALS lumbar onset, flail arm and leg and primary lateral sclerosis (PLS). Of the
      1834 registered patients, 1677 (90%) could be allocated a clinical phenotype. ALS
      bulbar onset had a significantly lower length of survival when compared with all
      other clinical phenotypes (p<0.004). There were delays in the median time to
      diagnosis of up to 12 months for the ALS phenotypes, 18 months for the flail limb
      phenotypes and 19 months for PLS. Riluzole treatment was started in 78-85% of
      cases. The median delays in initiating riluzole therapy, from symptom onset,
      varied from 10 to 12 months in the ALS phenotypes and 15-18 months in the flail
      limb phenotypes. Percutaneous endoscopic gastrostomy was implemented in 8-36% of
      ALS phenotypes and 2-9% of the flail phenotypes. Non-invasive ventilation was
      started in 16-22% of ALS phenotypes and 21-29% of flail phenotypes. CONCLUSIONS:
      The establishment of a cohort registry for ALS/MND is able to determine clinical
      phenotypes, survival and monitor time to key milestones in disease progression.
      It is intended to expand the cohort to a more population-based registry using opt
      out methodology and facilitate data linkage to other national registries.

PMID- 27694489
TI  - Effects of a nutrition plus exercise programme on physical function in sarcopenic
      obese elderly people: study protocol for a randomised controlled trial.
AB  - INTRODUCTION: With a rapidly ageing population, sarcopenic obesity, defined as
      decreased muscle mass and function combined with increased body fat, is a complex
      health problem. Although sarcopenic obesity contributes to a decline in physical
      function and exacerbates frailty in older adults, evidence from clinical trials
      about the effect of exercise and nutrition on this complex syndrome in Chinese
      older adults is lacking. METHODS AND ANALYSIS: We devised a study protocol for a
      single-blind randomised controlled trial. Sarcopenia is described as age-related
      decline in muscle mass plus low muscle strength and/or low physical performance.
      Obesity is defined as a percentage of body fat above the 60th centile. Ninety-two
      eligible participants will be randomly assigned to a control group, nutrition
      group, exercise group and nutrition plus exercise group to receive an 8-week
      intervention and 12-week follow-up. The primary outcomes will be the change in
      short physical performance battery scores, grip strength and 6 m usual gait
      speed. The secondary outcomes will include basic activities of daily living
      scores, instrumental activity daily living scores, body composition and body
      anthropometric indexes. For all main analyses, the principle of intention-to
      treat will be used. ETHICS AND DISSEMINATION: This study was approved by the
      medical ethics committee of Zhejiang Hospital on 25 November 2015. The study will
      present data targeting the clinical effects of nutrition and exercise on physical
      function and body composition in a Chinese older population with sarcopenic
      obesity. The results will help to provide important clinical evidence of the role
      of complex non-pharmaceutical interventions for sarcopenic obese older people.
      The findings of this study will be submitted to peer-reviewed medical journals
      for publication and presented at relevant academic conferences. TRIAL
      REGISTRATION NUMBER: ChiCTR-IOR-15007501; Pre-results.

PMID- 27694490
TI  - Effect of vitreomacular adhesion and vitreous gel on age-related reduction of
      macular thickness: a retrospective observational study.
AB  - OBJECTIVE: To investigate the effects of vitreomacular adhesion (VMA),
      vitreomacular separation (VMS) and absence of vitreous gel due to vitrectomy on
      macular thickness measured in the spectral domain optical coherence tomographic
      (SD-OCT) images. DESIGN: A longitudinal, retrospective, observational study.
      SETTING: Secondary multicentre study. PARTICIPANTS: 218 eyes of 218 healthy
      patients and 119 vitrectomised eyes of 119 patients were studied. The healthy
      individuals were classified into a VMA group (54 eyes) and a VMS group (164
      eyes), while the vitrectomised patients were classified into an internal limiting
      membrane (ILM)-on group (26 eyes) and an ILM-off group (93 eyes). In all
      participants, 2 Cirrus HD-OCT recordings were made with an average interval of 36
      months (range 24-60 months). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary
      outcome measure was the rate of change in macular thickness in the central
      sector. The secondary outcomes were the rates of change in macular thickness in
      the inner 4 sectors. RESULTS: The annual rate of change in the macular thickness
      of the central sector was 0.76+/-1.8 um/year in the VMA group, -0.58+/-2.3
      um/year in the VMS group, -1.57+/-1.9 um/year in the ILM-on group and -0.86+/-3.1
      um/year in the ILM-off group. There was a significant difference between the rate
      of the central sector thickness change in the VMA and VMS groups (p=0.0001). The
      presence of VMA was a significant factor associated with an increase in the
      central sector thickness (p=0.0055). When the healthy and ILM-on groups were
      compared, the rate of decrease in the central sector thickness was faster in the
      ILM-on group (p=0.0043). Multiple regression analyses showed that not peeling the
      ILM during the vitrectomy was a significant factor associated with a decrease in
      the central sector thickness (p=0.044). CONCLUSIONS: The presence of a VMA and a
      vitreous gel may help restrain the macular thickness reduction.

PMID- 27694492
TI  - Inositol-Triphosphate 3-Kinase C Mediates Inflammasome Activation and Treatment
      Response in Kawasaki Disease.
AB  - Kawasaki disease (KD) is a multisystem vasculitis that predominantly targets the
      coronary arteries in children. Phenotypic similarities between KD and recurrent
      fever syndromes point to the potential role of inflammasome activation in KD.
      Mutations in NLRP3 are associated with recurrent fever/autoinflammatory
      syndromes. We show that the KD-associated genetic polymorphism in inositol
      triphosphate 3-kinase C (ITPKC) (rs28493229) has important functional
      consequences, governing ITPKC protein levels and thereby intracellular calcium,
      which in turn regulates NLRP3 expression and production of IL-1beta and IL-18.
      Analysis of transcript abundance, protein levels, and cellular response profiles
      from matched, serial biospecimens from a cohort of genotyped KD subjects points
      to the critical role of ITPKC in mediating NLRP3 inflammasome activation.
      Treatment failure in those with the high-risk ITPKC genotype was associated with
      the highest basal and stimulated intracellular calcium levels and with increased
      cellular production of IL-1beta and IL-18 and higher circulating levels of both
      cytokines. Mechanistic studies using Itpkc-deficient mice in a disease model
      support the genomic, cellular, and clinical findings in affected children. Our
      findings provide the mechanism behind the observed efficacy of rescue therapy
      with IL-1 blockade in recalcitrant KD, and we identify that regulation of calcium
      mobilization is fundamental to the underlying immunobiology in KD.

PMID- 27694491
TI  - Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft
      versus-Host Disease.
AB  - Although chronic graft-versus-host disease (CGVHD) is the primary nonrelapse
      complication of allogeneic transplantation, understanding of its pathogenesis is
      limited. To identify the main operant pathways across the spectrum of CGVHD, we
      analyzed gene expression in circulating monocytes, chosen as in situ systemic
      reporter cells. Microarrays identified two interrelated pathways: 1) IFN
      inducible genes, and 2) innate receptors for cellular damage. Corroborating these
      with multiplex RNA quantitation, we found that multiple IFN-inducible genes
      (affecting lymphocyte trafficking, differentiation, and Ag presentation) were
      concurrently upregulated in CGVHD monocytes compared with normal subjects and non
      CGVHD control patients. IFN-inducible chemokines were elevated in both lichenoid
      and sclerotic CGHVD plasma and were linked to CXCR3+ lymphocyte trafficking.
      Furthermore, the levels of the IFN-inducible genes CXCL10 and TNFSF13B (BAFF)
      were correlated at both the gene and the plasma levels, implicating IFN induction
      as a factor in elevated BAFF levels in CGVHD. In the second pathway, damage
      /pathogen-associated molecular pattern receptor genes capable of inducing type I
      IFN were upregulated. Type I IFN-inducible MxA was expressed in proportion to
      CGVHD activity in skin, mucosa, and glands, and expression of TLR7 and DDX58
      receptor genes correlated with upregulation of type I IFN-inducible genes in
      monocytes. Finally, in serial analyses after transplant, IFN-inducible and damage
      response genes were upregulated in monocytes at CGVHD onset and declined upon
      therapy and resolution in both lichenoid and sclerotic CGVHD patients. This
      interlocking analysis of IFN-inducible genes, plasma analytes, and tissue
      immunohistochemistry strongly supports a unifying hypothesis of induction of IFN
      by innate response to cellular damage as a mechanism for initiation and
      persistence of CGVHD.

PMID- 27694493
TI  - MK2/3 Are Pivotal for IL-33-Induced and Mast Cell-Dependent Leukocyte Recruitment
      and the Resulting Skin Inflammation.
AB  - The IL-1R family member IL-33R mediates Fcepsilon-receptor-I (FcepsilonRI)
      independent activation of mast cells leading to NF-kappaB activation and
      consequently the production of cytokines. IL-33 also induces the activation of
      MAPKs, such as p38. We aimed to define the relevance of the p38-targets, the MAPK
      activated protein kinases 2 and 3 (MK2 and MK3) in IL-33-induced signaling and
      the resulting mast cell effector functions in vitro and in vivo. We demonstrate
      that the IL-33-induced IL-6 and IL-13 production strongly depends on the MK2/3
      mediated activation of ERK1/2 and PI3K signaling. Furthermore, in the presence of
      the stem cell factors, IL-33 did induce an MK2/3-, ERK1/2- and PI3K-dependent
      production of TNF-alpha. In vivo, the loss of MK2/3 in mast cells decreased the
      IL-33-induced leukocyte recruitment and the resulting skin inflammation.
      Therefore, the MK2/3-dependent signaling in mast cells is essential to mediate IL
      33-induced inflammatory responses. Thus, MK2/3 are potential therapeutic targets
      for suppression of IL-33-induced inflammation skin diseases such as psoriasis.

PMID- 27694494
TI  - Anandamide Suppresses Proinflammatory T Cell Responses In Vitro through Type-1
      Cannabinoid Receptor-Mediated mTOR Inhibition in Human Keratinocytes.
AB  - The endocannabinoid system comprises cannabinoid receptors 1 and 2 (CB1 and CB2),
      their endogenous ligands, anandamide (AEA) and 2-arachidonoylglycerol, and
      metabolic enzymes of these ligands. The endocannabinoid system has recently been
      implicated in the regulation of various pathophysiological processes of the skin
      that include immune competence and/or tolerance of keratinocytes, the disruption
      of which might promote the development of skin diseases. Recent evidence showed
      that CB1 in keratinocytes limits the secretion of proinflammatory chemokines,
      suggesting that this receptor might also regulate T cell dependent inflammatory
      diseases of the skin. In this article, we sought to investigate the cytokine
      profile of IFN-gamma-activated keratinocytes, and found that CB1 activation by
      AEA suppressed production and release of signature TH1- and TH17-polarizing
      cytokines, IL-12 and IL-23, respectively. We also set up cocultures between a
      conditioned medium of treated keratinocytes and naive T cells to disclose the
      molecular details that regulate the activation of highly proinflammatory TH1 and
      TH17 cells. AEA-treated keratinocytes showed reduced an induction of IFN-gamma
      producing TH1 and IL-17-producing TH17 cells, and these effects were reverted by
      pharmacological inhibition of CB1 Further analyses identified mammalian target of
      rapamycin as a proinflammatory signaling pathway regulated by CB1, able to
      promote either IL-12 and IL-23 release from keratinocytes or TH1 and TH17
      polarization. Taken together, these findings demonstrate that AEA suppresses
      highly pathogenic T cell subsets through CB1-mediated mammalian target of
      rapamycin inhibition in human keratinocytes. Thus, it can be speculated that the
      latter pathway might be beneficial to the physiological function of the skin, and
      can be targeted toward inflammation-related skin diseases.

PMID- 27694495
TI  - CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell-like
      Populations and Diverse Mononuclear Phagocytes.
AB  - CD4+ T cells are at the nexus of the innate and adaptive arms of the immune
      system. However, little is known about the evolutionary history of CD4+ T cells,
      and it is unclear whether their differentiation into specialized subsets is
      conserved in early vertebrates. In this study, we have created transgenic
      zebrafish with vibrantly labeled CD4+ cells allowing us to scrutinize the
      development and specialization of teleost CD4+ leukocytes in vivo. We provide
      further evidence that CD4+ macrophages have an ancient origin and had already
      emerged in bony fish. We demonstrate the utility of this zebrafish resource for
      interrogating the complex behavior of immune cells at cellular resolution by the
      imaging of intimate contacts between teleost CD4+ T cells and mononuclear
      phagocytes. Most importantly, we reveal the conserved subspecialization of
      teleost CD4+ T cells in vivo. We demonstrate that the ancient and specialized
      tissues of the gills contain a resident population of il-4/13b-expressing Th2
      like cells, which do not coexpress il-4/13a Additionally, we identify a
      contrasting population of regulatory T cell-like cells resident in the zebrafish
      gut mucosa, in marked similarity to that found in the intestine of mammals.
      Finally, we show that, as in mammals, zebrafish CD4+ T cells will infiltrate
      melanoma tumors and obtain a phenotype consistent with a type 2 immune
      microenvironment. We anticipate that this unique resource will prove invaluable
      for future investigation of T cell function in biomedical research, the
      development of vaccination and health management in aquaculture, and for further
      research into the evolution of adaptive immunity.

PMID- 27694496
TI  - Antibody Binding to CD4 Induces Rac GTPase Activation and Alters T Cell
      Migration.
AB  - The use of nondepleting Abs specific for CD4 and CD8 is an effective strategy to
      tolerize CD4+ and CD8+ T cells in a tissue-specific manner. We reported that
      coreceptor therapy reverses diabetes in new onset NOD mice. A striking feature of
      coreceptor-induced remission is the purging of T cells from the pancreatic lymph
      nodes (PLN) and islets of NOD mice. Evidence indicates that Abs binding to the
      coreceptors promotes T cell egress from these tissues. The present study examined
      how coreceptor therapy affects the migration of CD4+ T cells residing in the PLN
      of NOD mice. Anti-CD4 Ab treatment resulted in an increased frequency of PLN but
      not splenic CD4+ T cells that exhibited a polarized morphology consistent with a
      migratory phenotype. Furthermore, PLN CD4+ T cells isolated from anti-CD4 versus
      control Ab-treated animals displayed increased in vitro chemotaxis to
      chemoattractants such as sphingosine-1-phosphate and CXCL12. Notably, the latter
      was dependent on activation of the small Rho GTPases Rac1 and Rac2. Rac1 and Rac2
      activation was increased in Ab-bound CD4+ T cells from the PLN but not the
      spleen, and knockdown of Rac expression blocked the heightened reactivity of Ab
      bound PLN CD4+ T cells to CXCL12. Interestingly, Rac1 and Rac2 activation was
      independent of Rac guanine nucleotide exchange factors known to regulate T cell
      activity. Therefore, Ab binding to CD4 initiates a novel pathway that involves
      inflammation-dependent activation of Rac and establishment of altered T cell
      migratory properties.

PMID- 27694497
TI  - Unruptured intracranial aneurysm follow-up and treatment after morphological
      change is safe: observational study and systematic review.
AB  - BACKGROUND: The management of small unruptured incidentally discovered
      intracranial aneurysms (SUIAs) is still controversial. The aim of this study is
      to assess the safety of a management protocol of SUIAs, where selected cases with
      SUIAs are observed and secured only if signs of instability (growth) are
      documented. METHODS: A prospective consecutive cohort of 292 patients (2006-2014)
      and 368 SUIAs (anterior circulation aneurysms (ACs) smaller than 7 mm and
      posterior circulation aneurysms smaller than 4 mm without previous subarachnoid
      haemorrhage) was observed (mean follow-up time of 3.2 years and 1177.6 aneurysm
      years). Factors associated with aneurysm growth were systematically reviewed from
      the literature. RESULTS: The aneurysm growth probability was 2.6+/-0.1% per year.
      The rate of unexpected aneurysm rupture before treatment was 0.24% per year (95%
      CI 0.17% to 2.40%). The calculated rate of aneurysm rupture after growth was 6.3%
      per aneurysm-year (95% CI 1% to 22%). Aneurysms located in the posterior
      circulation and aneurysms with lobulation were more likely to grow. Females or
      patients suffering hypertension were more likely to have an aneurysm growing. The
      probability of aneurysms growth increased with the size of the dome and was
      proportional to the number of aneurysms diagnosed in a patient. CONCLUSIONS: It
      is safe to observe patients diagnosed with SUIAs using periodic imaging.
      Intervention to secure the aneurysm should be performed after growth is observed.

PMID- 27694498
TI  - Randomised feasibility study of physiotherapy for patients with functional motor
      symptoms.
AB  - OBJECTIVE: To determine the feasibility of conducting a randomised controlled
      trial of a specialist physiotherapy intervention for functional motor symptoms
      (FMS). METHODS: A randomised feasibility study was conducted recruiting patients
      with a clinically established diagnosis of FMS from a tertiary neurology clinic
      in London, UK. Participants were randomised to the intervention or a treatment as
      usual control. Measures of feasibility and clinical outcome were collected and
      assessed at 6 months. RESULTS: 60 individuals were recruited over a 9-month
      period. Three withdrew, leaving 29 intervention and 28 controls participants in
      the final analysis. 32% of patients with FMS met the inclusion criteria, of which
      90% enrolled. Acceptability of the intervention was high and there were no
      adverse events. At 6 months, 72% of the intervention group rated their symptoms
      as improved, compared to 18% in the control group. There was a moderate to large
      treatment effect across a range of outcomes, including three of eight Short Form
      36 (SF36) domains (d=0.46-0.79). The SF36 Physical function was found to be a
      suitable primary outcome measure for a future trial; adjusted mean difference
      19.8 (95% CI 10.2 to 29.5). The additional quality adjusted life years (QALY)
      with intervention was 0.08 (95% CI 0.03 to 0.13), the mean incremental cost per
      QALY gained was L12 087. CONCLUSIONS: This feasibility study demonstrated high
      rates of recruitment, retention and acceptability. Clinical effect size was
      moderate to large with high probability of being cost-effective. A randomised
      controlled trial is needed. TRIAL REGISTRATION NUMBER: NCT02275000; Results.

PMID- 27694499
TI  - The complex relationship of Tribbles pseudokinase 1, PML/RARA and C/EBPalpha in
      leukemia: two possible couples but not a trio.

PMID- 27694500
TI  - Matching inside and outside the HLA molecule in allogeneic hematopoietic stem
      cell transplantation.

PMID- 27694501
TI  - Advanced systemic mastocytosis: from molecular and genetic progress to clinical
      practice.
AB  - Systemic mastocytosis is a heterogeneous disease characterized by the
      accumulation of neoplastic mast cells in the bone marrow and other organ
      organs/tissues. Mutations in KIT, most frequently KIT D816V, are detected in over
      80% of all systemic mastocytosis patients. While most systemic mastocytosis
      patients suffer from an indolent disease variant, some present with more
      aggressive variants, collectively called "advanced systemic mastocytosis", which
      include aggressive systemic mastocytosis, systemic mastocytosis with an
      associated hematologic, clonal non mast cell-lineage disease, and mast cell
      leukemia. Whereas patients with indolent systemic mastocytosis have a near normal
      life expectancy, patients with advanced systemic mastocytosis have a reduced life
      expectancy. Although cladribine and interferon-alpha are of benefit in a group of
      patients with advanced systemic mastocytosis, no curative therapy is available
      for these patients except possible allogeneic hematopoietic stem cell
      transplantation. Recent studies have also revealed additional somatic defects
      (apart from mutations in KIT) in a majority of patients with advanced systemic
      mastocytosis. These include TET2, SRSF2, ASXL1, RUNX1, JAK2, and/or RAS
      mutations, which may adversely impact prognosis and survival in particular
      systemic mastocytosis with an associated hematological neoplasm. In addition,
      several additional signaling molecules involved in the abnormal proliferation of
      mast cells in systemic mastocytosis have been identified. These advances have led
      to a better understanding of the biology of advanced systemic mastocytosis and to
      the development of new targeted treatment concepts. Herein, we review the biology
      and pathogenesis of advanced systemic mastocytosis, with a special focus on novel
      molecular findings as well as current and evolving therapeutic options.

PMID- 27694503
TI  - Predicting outcome of patients with myelodysplastic syndromes after failure of
      azacitidine: validation of the North American MDS consortium scoring system.

PMID- 27694502
TI  - Catching up with solid tumor oncology: what is the evidence for a prognostic role
      of programmed cell death-ligand 1/programmed cell death-1 expression in B-cell
      lymphomas?
AB  - Therapeutic strategies targeting the programmed cell death-ligand 1/programmed
      cell death-1 pathway have shown significant responses and good tolerability in
      solid malignancies. Although preclinical studies suggest that inhibiting
      programmed cell death-ligand 1/programmed cell death-1 interactions might also be
      highly effective in hematological malignancies, remarkably few clinical trials
      have been published. Determining patients who will benefit most from programmed
      cell death-ligand 1/programmed cell death-1-directed immunotherapy and whether
      programmed cell death-ligand 1/programmed cell death-1 are adequate prognostic
      markers becomes an increasingly important clinical question, especially as
      aberrant programmed cell death-ligand 1/programmed cell death-1 expression are
      key mediators of impaired anti-tumor immune responses in a range of B-cell
      lymphomas. Herein, we systematically review the published literature on the
      expression and prognostic value of programmed cell death-ligand 1/programmed cell
      death-1 in these patients and identify considerable differences in expression
      patterns, distribution and numbers of programmed cell death-ligand 1+/programmed
      cell death-1+cells, both between and within lymphoma subtypes, which is reflected
      in conflicting findings regarding the prognostic value of programmed cell death
      ligand 1+/programmed cell death-1+ cells. This can be partly explained by
      differences in methodologies (techniques, protocols, cutoff values) and
      definitions of positivity. Moreover, lymphomagenesis, disease progression, and
      prognosis appear to be determined not only by the presence, numbers and
      distribution of specific subtypes of T cells, but also by other cells and
      additional immune checkpoints. Collectively, our findings indicate that
      programmed cell death-ligand 1/programmed cell death-1 interactions play an
      essential role in B-cell lymphoma biology and are of clinical importance, but
      that the overall outcome is determined by additional components. To categorize
      the exact prognostic value of programmed cell death-ligand 1/programmed cell
      death-1 expressing cells and cell types, efforts should be made to harmonize
      their assessment and interpretation, optimally within ongoing clinical immune
      checkpoint inhibitor trials, and to identify and validate novel high-throughput
      platforms.

PMID- 27694504
TI  - The higher prevalence of missense mutations in hemophilia B compared to
      hemophilia A could be important in determining a milder clinical phenotype in
      patients with severe hemophilia B.

PMID- 27694505
TI  - A contribution to the debate about the possible different clinical severity
      between hemophilia A and B.

PMID- 27694506
TI  - Evaluating High Release Rate MCH (3-Methylcyclohex-2-en-1-one) Treatments for
      Reducing Dendroctonus pseudotsugae (Coleoptera: Curculionidae) Infestations.
AB  - Current recommendations for applying the antiaggregation pheromone 3
      methylcyclohex-2-en-1-one (MCH) to protect live trees from Douglas-fir beetle,
      Dendroctonus pseudotsugae Hopkins, infestation are to space individual passive
      releasers (MCH bubble capsules) on a 12- by 12-m grid throughout areas to be
      protected. Previous field studies and a theoretical study using a puff dispersion
      model to predict pheromone concentrations have shown that releasers emitting
      higher rates of MCH spaced farther apart may be as effective as the established
      standard treatment. During 2012 and 2013, we tested higher release rates of MCH
      at correspondingly wider spacings to keep the total amount of MCH released per
      unit area equal in all treatments. In 2012 near Challis, ID, treatments included
      the established standard release rate and spacing, four and six times the
      standard release rate at correspondingly wider spacings, and an untreated
      control. In 2013 near Ketchum, ID, treatments included the established standard
      release rate and spacing, five and seven times the standard release rate at
      correspondingly wider spacings, and an untreated control. Results from both years
      indicated that all MCH treatments were equally effective in reducing Douglas-fir
      beetle infestation. Using higher release rate formulations at wider spacings will
      reduce labor costs of installing MCH treatments, and, in cases where it is
      necessary, retrieving the releasers as well. In addition to reducing labor costs,
      the revised treatment protocol may increase the feasibility of treating areas
      that currently may not be possible due to treatment costs.

PMID- 27694508
TI  - 40 years of the Oxford Knee.

PMID- 27694509
TI  - Radiological Decision Aid to determine suitability for medial unicompartmental
      knee arthroplasty: development and preliminary validation.
AB  - AIMS: An evidence-based radiographic Decision Aid for meniscal-bearing
      unicompartmental knee arthroplasty (UKA) has been developed and this study
      investigates its performance at an independent centre. PATIENTS AND METHODS: Pre
      operative radiographs, including stress views, from a consecutive cohort of 550
      knees undergoing arthroplasty (UKA or total knee arthroplasty; TKA) by a single
      surgeon were assessed. Suitability for UKA was determined using the Decision Aid,
      with the assessor blinded to treatment received, and compared with actual
      treatment received, which was determined by an experienced UKA surgeon based on
      history, examination, radiographic assessment including stress radiographs, and
      intra-operative assessment in line with the recommended indications as described
      in the literature. RESULTS: The sensitivity and specificity of the Decision Aid
      was 92% and 88%, respectively. Excluding knees where a clear pre-operative plan
      was made to perform TKA, i.e. patient request, the sensitivity was 93% and
      specificity 96%. The false-positive rate was low (2.4%) with all affected
      patients readily identifiable during joint inspection at surgery. In patients
      meeting Decision Aid criteria and receiving UKA, the five-year survival was 99%
      (95% confidence intervals (CI) 97 to 100). The false negatives (3.5%), who
      received UKA but did not meet the criteria, had significantly worse functional
      outcomes (flexion p < 0.001, American Knee Society Score - Functional p < 0.001,
      University of California Los Angeles score p = 0.04), and lower implant survival
      of 93.1% (95% CI 77.6 to 100). CONCLUSION: The radiographic Decision Aid safely
      and reliably identifies appropriate patients for meniscal-bearing UKA and
      achieves good results in this population. The widespread use of the Decision Aid
      should improve the results of UKA. Cite this article: Bone Joint J 2016;98-B(10
      Suppl B):3-10.

PMID- 27694510
TI  - Does location of patellofemoral chondral lesion influence outcome after Oxford
      medial compartmental knee arthroplasty?
AB  - AIMS: Medial unicompartmental knee arthroplasty (UKA) is associated with
      successful outcomes in carefully selected patient cohorts. We hypothesised that
      severity and location of patellofemoral cartilage lesions significantly
      influences functional outcome after Oxford medial compartmental knee
      arthroplasty. PATIENTS AND METHODS: We reviewed 100 consecutive UKAs at minimum
      eight-year follow-up (96 to 132). A single surgeon performed all procedures.
      Patients were selected based on clinical and plain radiographic assessment. All
      patients had end-stage medial compartment osteoarthritis (OA) with sparing of the
      lateral compartment and intact anterior cruciate ligaments. None of the patients
      had end-stage patellofemoral OA, but patients with anterior knee pain or partial
      thickness chondral loss were not excluded. There were 57 male and 43 female
      patients. The mean age at surgery was 69 years (41 to 82). At surgery the joint
      was carefully inspected for patellofemoral chondral loss and this was documented
      based on severity of cartilage loss (0 to 4 Outerbridge grading) and topographic
      location (medial, lateral, central, and superior or inferior). Functional scores
      collected included Oxford Knee Score (OKS), patient satisfaction scale and
      University College Hospital (UCH) knee score. Intraclass correlation was used to
      compare chondral damage to outcomes. RESULTS: All patients documented significant
      improvement in pain and improved functional scores at mid-term follow-up. There
      were four revisions (mean 2.9 years, 2 to 4; standard deviation (sd) 0.9) in this
      cohort, three for tibial loosening and one for femoral loosening. There was one
      infection that was treated with debridement and insert exchange. The mean OKS
      improved from 23.2 (sd 7.1) to 39.1 (sd 6.9); p < 0.001. The cohort with central
      and lateral grade 3 patellofemoral OA documented lower mean satisfaction with
      pain (90, sd 11.8) and function (87.5, sd 10.3) on the patient satisfaction
      scale. On the UCH scale, patients reported significantly decreased mean overall
      scores (7.3, sd 1.2 vs 9, sd 2.3) as well as stair climb task (3.5, sd 0.3 vs 5,
      sd 0.1) when cartilage lesions were located centrally or laterally on the PFJ.
      Patients with medial chondral PFJ lesions behave similar to patients with no
      chondral lesions. CONCLUSION: Topographical location and severity of cartilage
      damage of the patella can significantly influence function after successful
      Oxford medial UKA. Surgeons should factor this in when making their operative
      decision, and undertake to counsel patients appropriately. Cite this article:
      Bone Joint J 2016;98-B(10 Suppl B):11-15.

PMID- 27694511
TI  - Gait comparison of unicompartmental and total knee arthroplasties with healthy
      controls.
AB  - AIMS: To compare the gait of unicompartmental knee arthroplasty (UKA) and total
      knee arthroplasty (TKA) patients with healthy controls, using a machine-learning
      approach. PATIENTS AND METHODS: 145 participants (121 healthy controls, 12
      patients with cruciate-retaining TKA, and 12 with mobile-bearing medial UKA) were
      recruited. The TKA and UKA patients were a minimum of 12 months post-operative,
      and matched for pattern and severity of arthrosis, age, and body mass index.
      Participants walked on an instrumented treadmill until their maximum walking
      speed was reached. Temporospatial gait parameters, and vertical ground reaction
      force data, were captured at each speed. Oxford knee scores (OKS) were also
      collected. An ensemble of trees algorithm was used to analyse the data: 27 gait
      variables were used to train classification trees for each speed, with a binary
      output prediction of whether these variables were derived from a UKA or TKA
      patient. Healthy control gait data was then tested by the decision trees at each
      speed and a final classification (UKA or TKA) reached for each subject in a
      majority voting manner over all gait cycles and speeds. Top walking speed was
      also recorded. RESULTS: 92% of the healthy controls were classified by the
      decision tree as a UKA, 5% as a TKA, and 3% were unclassified. There was no
      significant difference in OKS between the UKA and TKA patients (p = 0.077). Top
      walking speed in TKA patients (1.6 m/s; 1.3 to 2.1) was significantly lower than
      that of both the UKA group (2.2 m/s; 1.8 to 2.7) and healthy controls (2.2 m/s;
      1.5 to 2.7; p < 0.001). CONCLUSION: UKA results in a more physiological gait
      compared with TKA, and a higher top walking speed. This difference in function
      was not detected by the OKS. Cite this article: Bone Joint J 2016;98-B(10 Suppl
      B):16-21.

PMID- 27694512
TI  - A survival analysis of 1084 knees of the Oxford unicompartmental knee
      arthroplasty: a comparison between consultant and trainee surgeons.
AB  - AIMS: The aim of this to study was to compare the previously unreported long-term
      survival outcome of the Oxford medial unicompartmental knee arthroplasty (UKA)
      performed by trainee surgeons and consultants. PATIENTS AND METHODS: We therefore
      identified a previously unreported cohort of 1084 knees in 947 patients who had a
      UKA inserted for anteromedial knee arthritis by consultants and surgeons in
      training, at a tertiary arthroplasty centre and performed survival analysis on
      the group with revision as the endpoint. RESULTS: The ten-year cumulative
      survival rate for revision or exchange of any part of the prosthetic components
      was 93.2% (95% confidence interval (CI) 86.1 to 100, number at risk 45).
      Consultant surgeons had a nine-year cumulative survival rate of 93.9% (95% CI
      90.2 to 97.6, number at risk 16). Trainee surgeons had a cumulative nine-year
      survival rate of 93.0% (95% CI 90.3 to 95.7, number at risk 35). Although there
      was no differences in implant survival between consultants and trainees (p =
      0.30), there was a difference in failure pattern whereby all re-operations
      performed for bearing dislocation (n = 7), occurred in the trainee group. This
      accounted for 0.6% of the entire cohort and 15% of the re-operations. CONCLUSION:
      This is the largest single series of the Oxford UKA ever reported and
      demonstrates that good results can be achieved by a heterogeneous group of
      surgeons, including trainees, if performed within a high-volume centre with
      considerable experience with the procedure. Cite this article: Bone Joint J
      2016;(10 Suppl B):22-7.

PMID- 27694513
TI  - Early outcomes of twin-peg mobile-bearing unicompartmental knee arthroplasty
      compared with primary total knee arthroplasty.
AB  - AIMS: Since redesign of the Oxford phase III mobile-bearing unicompartmental knee
      arthroplasty (UKA) femoral component to a twin-peg design, there has not been a
      direct comparison to total knee arthroplasty (TKA). Thus, we explored differences
      between the two cohorts. PATIENTS AND METHODS: A total of 168 patients (201
      knees) underwent medial UKA with the Oxford Partial Knee Twin-Peg. These patients
      were compared with a randomly selected group of 177 patients (189 knees) with
      primary Vanguard TKA. Patient demographics, Knee Society (KS) scores and range of
      movement (ROM) were compared between the two cohorts. Additionally, revision, re
      operation and manipulation under anaesthesia rates were analysed. RESULTS: The
      mean follow-up for UKA and TKA groups was 5.4 and 5.5 years, respectively. Six
      TKA (3.2%) versus three UKAs (1.5%) were revised which was not significant (p =
      0.269). Manipulation was more frequent after TKA (16; 8.5%) versus none in the
      UKA group (p < 0.001). UKA patients had higher post-operative KS function scores
      versus TKA patients (78 versus 66, p < 0.001) with a trend toward greater
      improvement, but there was no difference in ROM and KS clinical improvement (p =
      0.382 and 0.420, respectively). CONCLUSION: We found fewer manipulations, and
      higher functional outcomes for patients treated with medial mobile-bearing UKA
      compared with TKA. TKA had twice the revision rate as UKA although this did not
      reach statistical significance with the numbers available. Cite this article:
      Bone Joint J 2016;98-B(10 Suppl B):28-33.

PMID- 27694514
TI  - The results of Oxford unicompartmental knee arthroplasty in the United States: a
      mean ten-year survival analysis.
AB  - AIMS: Approved by the Food and Drug Administration in 2004, the Phase III Oxford
      Medial Partial Knee is used to treat anteromedial osteoarthritis (AMOA) in
      patients with an intact anterior cruciate ligament. This unicompartmental knee
      arthroplasty (UKA) is relatively new in the United States, and therefore long
      term American results are lacking. PATIENTS AND METHODS: This is a single
      surgeon, retrospective study based on prospectively collected data, analysing a
      consecutive series of primary UKAs using the Phase III mobile-bearing Oxford Knee
      and Phase III instrumentation. Between July 2004 and December 2006, the senior
      author (RHE) carried out a medial UKA in 173 patients (213 knees) for
      anteromedial osteoarthritis or avascular necrosis (AVN). A total of 95 patients
      were men and 78 were women. Their mean age at surgery was 67 years (38 to 89) and
      mean body mass index 29.87 kg/m2 (17 to 62). The mean follow-up was ten years (4
      to 11). RESULTS: Survivorship of the Oxford UKA at ten years was 88%, using life
      table analysis. Implant survivorship at ten years was 95%. The most common cause
      for revision was the progression of osteoarthritis in the lateral compartment.
      The mean knee score element of the American Knee Society Score (AKSS) was 50 pre
      operatively and increased to 93 post-operatively. The mean AKSS function score
      was 56 pre-operatively rising to 78 post-operatively CONCLUSION: This ten-year
      follow-up study of the Oxford UKA undertaken in the United States shows good
      survivorship and excellent function in a wide selection of patients with AMOA and
      AVN. Cite this article: Bone Joint J 2016;98-B(10 Suppl B):34-40.

PMID- 27694518
TI  - Our Future Selves: Unprecedented Opportunities.

PMID- 27694515
TI  - Ten- to 15-year results of the Oxford Phase III mobile unicompartmental knee
      arthroplasty: a prospective study from a non-designer group.
AB  - AIMS: The interest in unicompartmental knee arthroplasty (UKA) for medial
      osteoarthritis has increased rapidly but the long-term follow-up of the Oxford
      UKAs has yet to be analysed in non-designer centres. We have examined our ten- to
      15-year clinical and radiological follow-up data for the Oxford Phase III UKAs.
      PATIENTS AND METHODS: Between January 1999 and January 2005 a total of 138
      consecutive Oxford Phase III arthroplasties were performed by a single surgeon in
      129 patients for medial compartment osteoarthritis (71 right and 67 left knees,
      mean age 72.0 years (47 to 91), mean body mass index 28.2 (20.7 to 52.2)). Both
      clinical data and radiographs were prospectively recorded and obtained at
      intervals. Of the 129 patients, 32 patients (32 knees) died, ten patients (12
      knees) were not able to take part in the final clinical and radiological
      assessment due to physical and mental conditions, but via telephone interview it
      was confirmed that none of these ten patients (12 knees) had a revision of the
      knee arthroplasty. One patient (two knees) was lost to follow-up. RESULTS: The
      mean follow-up was 11.7 years (10 to 15). A total of 11 knees (8%) were revised.
      The survival at 15 years with revision for any reason as the endpoint was 90.6%
      (95% confidence interval (CI) 85.2 to 96.0) and revision related to the
      prosthesis was 99.3% (95% CI 97.9 to 100). The mean total Knee Society Score was
      47 (0 to 80) pre-operatively and 81 (30 to 100) at latest follow-up. The mean
      Oxford Knee Score was 19 (12 to 40) pre-operatively and 42 (28 to 55) at final
      follow-up. Radiolucency beneath the tibial component occurred in 22 of 81
      prostheses (27.2%) without evidence of loosening. CONCLUSION: This study supports
      the use of UKA in medial compartment osteoarthritis with excellent long-term
      functional and radiological outcomes with an excellent 15-year survival rate.
      Cite this article: Bone Joint J 2016;98-B(10 Suppl B):41-7.

PMID- 27694520
TI  - On "Treatment-Based Classification System for Low Back Pain: Revision and
      Update." Alrwaily M, Timko M, Schneider M, et al. Phys Ther. 2016;96:1057-1066.

PMID- 27694519
TI  - Toward a Transformed Understanding: From Pain and Movement to Pain With Movement.

PMID- 27694523
TI  - Plant glycobiology: a current snap shot!

PMID- 27694521
TI  - Mutations in the phosphatidylinositol glycan C (PIGC) gene are associated with
      epilepsy and intellectual disability.
AB  - BACKGROUND: Of our 1400 exome-studied patients, 67% originate from consanguineous
      families. ~80% suffer from variable degree of intellectual disability (ID). The
      search for disease causing genes using homozygosity mapping was progressing
      slowly until 2010, then markedly accelerated by the introduction of exome
      analysis. OBJECTIVES: To identify the disease causing mutation(s) in three
      patients from two unrelated families who suffered from global developmental
      delay, severe ID and drug-responsive seizure disorder. METHODS: Exome analysis
      was performed in DNA of the three patients. The identified PIGC variants were
      generated and transfected into PIGC-defective mouse cells and the restoration of
      the surface expression of mouse CD90, CD48 and FLAER was assessed using flow
      cytometry. The expression of these proteins was also studied on the surface of
      patients' leucocytes. RESULTS: Three PIGC mutations were identified; homozygous
      p.L189W in one family and compound heterozygosity for p.L212P/p.R21X variants in
      another. PIGC participates in the biosynthesis of the
      glycosylphosphatidylinositol (GPI) anchor which tethers proteins to plasma
      membrane. In cells lacking PIGC protein, which were transfected with each of the
      PIGC variants, we detected a clear reduction of surface expression of GPI
      anchored proteins. Furthermore, analyses of patients' leucocytes showed
      significant and constant decrease of CD16 surface expression in granulocytes, and
      moderate decrease of CD14, CD55, CD59 and FLAER levels. CONCLUSIONS: PIGC joins
      the list of genes in which mutations result in defective biosynthesis of GPI
      anchoring, manifesting by global developmental delay and seizure disorder. The
      lack of specific biomarker dictates exome sequencing as the diagnostic procedure
      of choice in similar patients.

PMID- 27694524
TI  - Phytochelatin Synthesis Promotes Leaf Zn Accumulation of Arabidopsis thaliana
      Plants Grown in Soil with Adequate Zn Supply and is Essential for Survival on Zn
      Contaminated Soil.
AB  - Phytochelatin (PC) synthesis is essential for the detoxification of non-essential
      metals such as cadmium (Cd). In vitro experiments with Arabidopsis thaliana
      seedlings had indicated a contribution to zinc (Zn) tolerance as well. We
      addressed the physiological role of PC synthesis in Zn homeostasis of plants
      under more natural conditions. Growth responses, PC accumulation and leaf ionomes
      of wild-type and AtPCS1 mutant plants cultivated in different soils representing
      adequate Zn supply, Zn deficiency and Zn excess were analyzed. Growth on Zn
      contaminated soil triggers PC synthesis and is strongly impaired in PC-deficient
      mutants. In fact, the contribution of AtPCS1 to tolerating Zn excess is
      comparable with that of the major Zn tolerance factor MTP1. For plants supplied
      with a normal level of Zn, a significant reduction in leaf Zn accumulation of
      AtPCS1 mutants was detected. In contrast, AtPCS1 mutants grown under Zn-limited
      conditions showed wild-type levels of Zn accumulation, suggesting the operation
      of distinct Zn translocation pathways. Contrasting phenotypes of the tested
      AtPCS1 mutant alleles upon growth in Zn- or Cd-contaminated soil indicated
      differential activation of PC synthesis by these metals. Experiments with
      truncated versions identified a part of the AtPCS1 protein required for the
      activation by Zn but not by Cd.

PMID- 27694525
TI  - Clade IVa Basic Helix-Loop-Helix Transcription Factors Form Part of a Conserved
      Jasmonate Signaling Circuit for the Regulation of Bioactive Plant Terpenoid
      Biosynthesis.
AB  - Plants produce many bioactive, specialized metabolites to defend themselves when
      facing various stress situations. Their biosynthesis is directed by a tightly
      controlled regulatory circuit that is elicited by phytohormones such as jasmonate
      (JA). The basic helix-loop-helix (bHLH) transcription factors (TFs) bHLH iridoid
      synthesis 1 (BIS1) and Triterpene Saponin Activating Regulator (TSAR) 1 and 2,
      from Catharanthus roseus and Medicago truncatula, respectively, all belong to
      clade IVa of the bHLH protein family and activate distinct terpenoid pathways,
      thereby mediating monoterpenoid indole alkaloid (MIA) and triterpene saponin (TS)
      accumulation, respectively, in these two species. In this study, we report that
      promoters of the genes encoding the enzymes involved in the specific terpenoid
      pathway of one of these species can be transactivated by the orthologous bHLH
      factor from the other species through recognition of the same cis-regulatory
      elements. Accordingly, ectopic expression of CrBIS1 in M. truncatula hairy roots
      up-regulated the expression of all genes required for soyasaponin production,
      resulting in strongly increased levels of soyasaponins in the transformed roots.
      Likewise, transient expression of MtTSAR1 and MtTSAR2 in C. roseus petals led to
      up-regulation of the genes involved in the iridoid branch of the MIA pathway.
      Together, our data illustrate the functional similarity of these JA-inducible TFs
      and indicate that recruitment of defined cis-regulatory elements constitutes an
      important aspect of the evolution of conserved regulatory modules for the
      activation of species-specific terpenoid biosynthesis pathways by common signals
      such as the JA phytohormones.

PMID- 27694526
TI  - Motor unit number estimates and neuromuscular transmission in the tibialis
      anterior of master athletes: evidence that athletic older people are not spared
      from age-related motor unit remodeling.
AB  - Muscle motor unit numbers decrease markedly in old age, while remaining motor
      units are enlarged and can have reduced neuromuscular junction transmission
      stability. However, it is possible that regular intense physical activity
      throughout life can attenuate this remodeling. The aim of this study was to
      compare the number, size, and neuromuscular junction transmission stability of
      tibialis anterior (TA) motor units in healthy young and older men with those of
      exceptionally active master runners. The distribution of motor unit potential
      (MUP) size was determined from intramuscular electromyographic signals recorded
      in healthy male Young (mean +/- SD, 26 +/- 5 years), Old (71 +/- 4 years) and
      Master Athletes (69 +/- 3 years). Relative differences between groups in numbers
      of motor units was assessed using two methods, one comparing MUP size and muscle
      cross-sectional area (CSA) determined with MRI, the other comparing surface
      recorded MUPs with maximal compound muscle action potentials and commonly known
      as a "motor unit number estimate (MUNE)". Near fiber (NF) jiggle was measured to
      assess neuromuscular junction transmission stability. TA CSA did not differ
      between groups. MUNE values for the Old and Master Athletes were 45% and 40%,
      respectively, of the Young. Intramuscular MUPs of Old and Master Athletes were
      43% and 56% larger than Young. NF jiggle was slightly higher in the Master
      Athletes, with no difference between Young and Old. These results show
      substantial and similar motor unit loss and remodeling in Master Athletes and Old
      individuals compared with Young, which suggests that lifelong training does not
      attenuate the age-related loss of motor units.

PMID- 27694527
TI  - Videomicroscopy as a tool for investigation of the microcirculation in the
      newborn.
AB  - The perinatal period remains a time of significant risk of death or disability.
      Increasing evidence suggests that this depends on microcirculatory behavior.
      Sidestream dark-field orthogonal polarized light videomicroscopy (OPS) has
      emerged as a useful assessment of adult microcirculation but the values derived
      are not delineated for the newborn. We aimed to define these parameters in well
      term newborn infants. Demographic details were collected prospectively on 42
      healthy term neonates (n = 20 females, n = 22 males). OPS videomicroscopy
      (Microscan) was used to view ear conch skin microcirculation at 6, 24, and 72 h
      of age. Stored video was analyzed by a masked observer using proprietary
      software. There were no significant differences between the sexes for any
      structural parameters at any time point. There was a significant increase over
      time in small vessel perfusion in female infants only (P = 0.009). A number of 6-
      and 72-h measurements were significantly correlated, but differed from the 24-h
      values. These observations confirm the utility of the ear conch for neonatal
      microvascular videomicroscopy. They provide a baseline for studies into the use
      of OPS videomicroscopy in infants. The changes observed are comparable with
      previous studies of term infants using these and other microvascular techniques.
      It is recommended that studies for examining the mature neonatal microvascular
      structure be delayed until 72 h of life, but studies of the physiology of
      cardiovascular transition should include the 24-h time point after delivery.

PMID- 27694528
TI  - Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative
      to tricarboxylic acid cycle capacity in young, healthy low birth weight men.
AB  - We hypothesized that an increased, incomplete fatty acid beta-oxidation in
      mitochondria could be part of the metabolic events leading to insulin resistance
      and thereby an increased type 2 diabetes risk in low birth weight (LBW) compared
      with normal birth weight (NBW) individuals. Therefore, we measured fasting plasma
      levels of 45 acylcarnitine species in 18 LBW and 25 NBW men after an isocaloric
      control diet and a 5-day high-fat, high-calorie diet. We demonstrated that LBW
      men had higher C2 and C4-OH levels after the control diet compared with NBW men,
      indicating an increased fatty acid beta-oxidation relative to the tricarboxylic
      acid cycle flux. Also, they had higher C6-DC, C10-OH/C8-DC, and total hydroxyl
      /dicarboxyl-acylcarnitine levels, which may suggest an increased fatty acid omega
      oxidation in the liver. Furthermore, LBW and NBW men decreased several
      acylcarnitine levels in response to overfeeding, which is likely a result of an
      upregulation of fatty acid oxidation due to the dietary challenge. Moreover, C10
      OH/C8-DC and total hydroxyl-/dicarboxyl-acylcarnitine levels tended to be
      negatively associated with the serum insulin level, and the total hydroxyl
      /dicarboxyl-acylcarnitine level additionally tended to be negatively associated
      with the hepatic insulin resistance index. This indicates that an increased fatty
      acid omega-oxidation could be a compensatory mechanism to prevent an accumulation
      of lipid species that impair insulin signaling.

PMID- 27694529
TI  - Reduced mitochondrial mass and function add to age-related susceptibility toward
      diet-induced fatty liver in C57BL/6J mice.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a major health burden in the aging
      society with an urging medical need for a better understanding of the underlying
      mechanisms. Mitochondrial fatty acid oxidation and mitochondrial-derived reactive
      oxygen species (ROS) are considered critical in the development of hepatic
      steatosis, the hallmark of NAFLD. Our study addressed in C57BL/6J mice the effect
      of high fat diet feeding and age on liver mitochondria at an early stage of NAFLD
      development. We therefore analyzed functional characteristics of hepatic
      mitochondria and associated alterations in the mitochondrial proteome in response
      to high fat feeding in adolescent, young adult, and middle-aged mice.
      Susceptibility to diet-induced obesity increased with age. Young adult and middle
      aged mice developed fatty liver, but not adolescent mice. Fat accumulation was
      negatively correlated with an age-related reduction in mitochondrial mass and
      aggravated by a reduced capacity of fatty acid oxidation in high fat-fed mice.
      Irrespective of age, high fat diet increased ROS production in hepatic
      mitochondria associated with a balanced nuclear factor erythroid-derived 2 like 2
      (NFE2L2) dependent antioxidative response, most likely triggered by reduced
      tethering of NFE2L2 to mitochondrial phosphoglycerate mutase 5. Age indirectly
      influenced mitochondrial function by reducing mitochondrial mass, thus
      exacerbating diet-induced fat accumulation. Therefore, consideration of age in
      metabolic studies must be emphasized.

PMID- 27694530
TI  - AT-RvD1 combined with DEX is highly effective in treating TNF-alpha-mediated
      disruption of the salivary gland epithelium.
AB  - Sjogren's syndrome (SS) is an autoimmune disorder characterized by chronic
      inflammation and destruction of salivary and lacrimal glands leading to dry mouth
      and dry eyes, respectively. Currently, the etiology of SS is unknown and the
      current therapies have no permanent benefit; therefore, new approaches are
      necessary to effectively treat this condition. Resolvins are highly potent
      endogenous lipid mediators that are synthesized during the resolution of
      inflammation to restore tissue homeostasis. Previous studies indicate that the
      resolvin family member, RvD1, binds to the ALX/FPR2 receptor to block
      inflammatory signals caused by tumor necrosis factor-alpha (TNF-alpha) in the
      salivary epithelium. More recently, the corticosteroid, dexamethasone (DEX), was
      shown to be effective in reducing salivary gland inflammation. However, DEX, as
      with other corticosteroids, elicits adverse secondary effects that could be
      ameliorated when used in smaller doses. Therefore, we investigated whether the
      more stable aspirin-triggered (AT) epimer, AT-RvD1, combined with reduced doses
      of DEX is effective in treating TNF-alpha-mediated disruption of polarized rat
      parotid gland (Par-C10) epithelial cell clusters. Our results indicate that AT
      RvD1 and DEX individually reduced TNF-alpha-mediated alteration in the salivary
      epithelium (i.e, maintained cell cluster formation, increased lumen size, reduced
      apoptosis, and preserved cell survival signaling responses) as compared to
      untreated cells. Furthermore, AT-RvD1 combined with a reduced dose of DEX
      produced stronger responses (i.e., robust salivary cell cluster formation, larger
      lumen sizes, further reduced apoptosis, and sustained survival signaling
      responses) as compared to those observed with individual treatments. These
      studies demonstrate that AT-RvD1 combined with DEX is highly effective in
      treating TNF-alpha-mediated disruption of salivary gland epithelium.

PMID- 27694531
TI  - Anodal transcranial direct current stimulation over right dorsolateral prefrontal
      cortex alters decision making during approach-avoidance conflict.
AB  - Approach-avoidance conflict (AAC) refers to situations associated with both
      rewarding and threatening outcomes. The AAC task was developed to measure AAC
      decision-making. Approach behavior during this task has been linked to self
      reported anxiety sensitivity and has elicited anterior cingulate, insula, caudate
      and right dorsolateral prefrontal cortex (dlPFC) activity, with right lateral PFC
      tracking the extent of approach behavior. Guided by these results, we used
      excitatory transcranial direct current stimulation (tDCS) to demonstrate the
      causal involvement of right dlPFC in AAC decision-making. Participants received
      anodal tDCS at 1.5mA over either left or right dlPFC or sham stimulation, while
      performing the AAC task and a control short-term memory task. Analyses of
      variance (ANOVA) revealed that for individuals with high anxiety sensitivity
      excitatory right (but not left or sham) dlPFC stimulation elicited measurable
      decreases in approach behavior during conflict. Excitatory left (but not right or
      sham) dlPFC simulation improved performance on the control task. These results
      support a possible asymmetry between the contributions of right and left dlPFC to
      AAC resolution during emotional decision-making. Increased activity in right
      dlPFC may contribute to anxiety-related symptoms and, as such, serve as a
      neurobehavioral target of anxiolytic treatments aiming to decrease avoidance
      behavior.

PMID- 27694532
TI  - Heart rate at admission is a predictor of in-hospital mortality in patients with
      acute coronary syndromes: Results from 58 European hospitals: The European
      Hospital Benchmarking by Outcomes in acute coronary syndrome Processes study.
AB  - AIMS: The purpose of this study was to investigate the relationship between heart
      rate at admission and in-hospital mortality in patients with ST-segment elevation
      myocardial infarction (STEMI) and non-ST-segment elevation acute coronary
      syndrome (NSTE-ACS). METHODS: Consecutive ACS patients admitted in 2008-2010
      across 58 hospitals in six participant countries of the European Hospital
      Benchmarking by Outcomes in ACS Processes (EURHOBOP) project (Finland, France,
      Germany, Greece, Portugal and Spain). Cardiogenic shock patients were excluded.
      Associations between heart rate at admission in categories of 10 beats per min
      (bpm) and in-hospital mortality were estimated by logistic regression in crude
      models and adjusting for age, sex, obesity, smoking, hypertension, diabetes,
      known heart failure, renal failure, previous stroke and ischaemic heart disease.
      In total 10,374 patients were included. RESULTS: In both STEMI and NSTE-ACS
      patients, a U-shaped relationship between admission heart rate and in-hospital
      mortality was found. The lowest risk was observed for heart rates between 70-79
      bpm in STEMI and 60-69 bpm in NSTE-ACS; risk of mortality progressively increased
      with lower or higher heart rates. In multivariable models, the relationship
      persisted but was significant only for heart rates >80 bpm. A similar
      relationship was present in both patients with or without diabetes, above or
      below age 75 years, and irrespective of the presence of atrial fibrillation or
      use of beta-blockers. CONCLUSION: Heart rate at admission is significantly
      associated with in-hospital mortality in patients with both STEMI and NSTE-ACS.
      ACS patients with admission heart rate above 80 bpm are at highest risk of in
      hospital mortality.

PMID- 27694533
TI  - Pokemon GO: Imaginary Creatures, Tangible Risks.

PMID- 27694534
TI  - Pain Among Community-Dwelling Older Adults with Dementia: Factors Associated with
      Undertreatment.
AB  - Objective: To identify factors associated with no analgesic treatment in
      community-dwelling older adults with mild-to-moderate dementia and moderate-to
      severe pain. Design: Secondary analysis of a randomized controlled trial.
      Setting: Michael E. DeBakey Veterans Affairs Medical Center. Subjects: Two
      hundred and two older adults (mean age = 79.27 years). Methods: Guided by the
      Behavioral Model of Health Service Utilization, participants completed
      questionnaires regarding predisposing (age, gender, race, educational level, care
      partner relationship), enabling (income), and need (pain interference, depressive
      symptoms, cognitive functioning) characteristics. Results: Hierarchical logistic
      regression analyses revealed that participants with greater income (odds ratio
      [OR] = 0.79, 95% confidence interval [CI] = 0.63-0.99) and greater pain
      interference (OR = 0.79, 95% CI = 0.63-0.99) were less likely to have no
      analgesic treatment. We also examined whether other factors such as depressive
      symptoms influenced the relationship between pain interference and pain
      treatment. Those with less pain interference were more likely to have no
      analgesic treatment (OR = 1.04, 95% CI = 1.01-1.08), but only if they had lower
      levels of depressive symptoms (b = -0.52, P  = 0.005). Conclusion: The initiation
      of analgesic trials is complicated for individuals with dementia and comorbid
      pain and depressive symptomology. Future research should focus on identifying the
      most effective assessment and treatment procedures to best direct clinical care
      for this population.

PMID- 27694535
TI  - Sinus Penetration of a Pulsating Device Versus the Classic Squeeze Bottle in
      Cadavers Undergoing Sinus Surgery.
AB  - OBJECTIVES: Nasal irrigation is standard in the management of chronic
      rhinosinusitis both before and after surgical intervention. Numerous irrigation
      devices are commercially available. The aim of this study was to compare the
      efficacy of a handheld pulse irrigation device against the gold standard manual
      squeeze bottle after endoscopic sinus surgery (ESS). METHODS: Five cadaveric
      specimens were prepared with video visualization ports into each sinus.
      Endoscopic sinus surgery was performed on each cadaver from minimal to maximal
      dissection. Sinuses were irrigated with fluorescein solution using both devices
      following each dissection. The irrigations were video recorded. A blinded
      independent observer scored each irrigation according to a defined scale.
      RESULTS: Comparison of the 2 devices using an intraclass correlation coefficient
      (ICC = 0.39) showed the 2 systems differed. Observation of individual sinuses
      showed the squeeze bottle consistently provided greater irrigation in the
      maxillary (P < .006), frontal (P < .0001), and sphenoid (P < .0001) sinuses.
      Pulse irrigation improved only in the maxillary sinus following ESS. CONCLUSION:
      The squeeze bottle consistently demonstrated superior irrigation in both native
      and operated conditions. Interestingly, saline penetration was not significantly
      improved after opening of the frontal and sphenoid sinuses. This is likely due to
      decreased backpressure in the nasal passage after opening the sinus cavities.

PMID- 27694537
TI  - Microangiopathic antiphospholipid antibody-associated syndrome in a pregnant
      lady.
AB  - We describe a gravid 37-year-old Chinese lady with known triple positive primary
      antiphospholipid syndrome with previous recurrent deep vein thrombosis and early
      spontaneous miscarriages. She was managed with low-molecular weight heparin,
      aspirin, hydroxychloroquine, prednisolone and monthly intravenous immunoglobulin.
      She presented with recurrent per-vaginal bleeding at 22 weeks of gestation and
      was found to have abruptio placentae. Anti-coagulation was held off. She
      subsequently delivered a stillborn at 24 weeks and anti-coagulation was
      restarted. Day 5 post-delivery, she developed HELLP, with hemolytic anaemia (Hb
      10.1 g/dL, haptoglobin <30 g/L, LDH 2206 U/L), elevated transaminases (AST 1196
      U/L, ALT 1130 U/L) and thrombocytopenia (platelet 28 * 10^9/L). There were also
      episodes of acute severe headache and abdominal pain assessed to be secondary to
      microvascular ischemia as CT did not reveal any thrombosis. Her blood pressure
      hovered persistently above systolic 180 mmHg, and required at least three anti
      hypertensives. These were coupled with a new onset proteinuria of 2 to 3 g/day.
      There was no evidence of disseminated intravascular coagulation. She was assessed
      to have microangiopathic antiphospholipid syndrome and was started on
      plasmapheresis. On Day 10 post-partum, the patient complained of foul-smelling
      vaginal discharge and was found to have retained products of conception, which
      was immediately evacuated. Her course was followed by poly-microbial sepsis
      secondary to Enterococcus fecalis, Klebsiella Pneumoniae and Escherichia coli.
      The patient was further treated with imipenem and she completed eight exchanges
      of plasmapheresis followed by five days of intravenous immunoglobulins with good
      clinical and biochemical improvement.

PMID- 27694536
TI  - Laryngotracheal Stenosis in Children and Infants With Neurological Disorders:
      Management and Outcome.
AB  - INTRODUCTION: The goal of this retrospective study is to compare the management
      and outcome of surgical treatment of laryngotracheal stenosis in children and
      infants with and without an associated neurological disorder. PATIENTS AND
      METHOD: In a series of children operated on for subglottic stenosis (SGS),
      patients with an associated neurological disorder were identified. The following
      criteria were compared in children with and without neurological disease: grade
      of stenosis, age, technique (Crico-Tracheal Resection (CTR), Laryngo-Tracheo
      Plasty (LTP) in single and 2 stage, laser), analyzing duration, preoperative
      tracheostomy, decannulation rate, preoperative gastrostomy, and number of days in
      intensive care unit and in hospital. RESULTS: Two hundred twenty-three children
      were operated on for subglottic stenosis, of whom 68 (30.5%) had an associated
      neurological disorder. Some criteria were found to be statistically different
      between the 2 populations: mean age of 43 months in neurological population
      versus 13 months (P < .001). The distribution of the grades of SGS appeared
      similar in the 2 groups (P = .088), and the mean duration of stay in hospital and
      in ICU were not statistically different (respectively, P = .186 and P = .056)
      between the 2 groups; a 2-stage procedure was performed more frequently than 1
      stage in the cases with associated neurological disorder-66.6% versus 36.5% (P =
      .013); the median duration of stenting was 20 days in those with neurological
      disease versus 12 (P = .021). Preoperative tracheotomy was noted in 75% of
      neurological patients versus 47.7% of the others (P < .001). The outcome was
      considered to be good (decannulation and no further treatment) following a single
      procedure in 82.4% of patients with neurological disorder, as against 86.5% of
      neurologically unimpaired subjects. The difference in outcome of surgery was not
      statistically different (P = .392) between the 2 groups. DISCUSSION AND
      CONCLUSION: It appears that subglottic stenosis in children with associated
      neurological disorder is not more severe than in neurologically normal patients.
      In three-quarters of the neurologically impaired cases, a preoperative
      tracheostomy was needed, but the rates of failure of postoperative decannulation
      are not statistically significant between the 2 groups. In our experience, 2
      stage techniques are more often performed than single stage in this population in
      order to allow airway safety, for example after feeding. If properly managed, the
      final results are similar in the 2 populations.

PMID- 27694538
TI  - Tumours and the heart: common risk factors, chemotherapy, and radiation.

PMID- 27694539
TI  - An ESC position paper on cardio-oncology.

PMID- 27694540
TI  - The evolving field of cardio-oncology: beyond anthracyclines and heart failure.

PMID- 27694542
TI  - Cardiac follow-up of cancer survivors.

PMID- 27694541
TI  - Cardiovascular side effects of small molecule therapies for cancer.

PMID- 27694544
TI  - European Heart Journal: cardiovascular pharmacotherapy.

PMID- 27694543
TI  - Specific risk of atrial fibrillation and stroke in oncology patients.

PMID- 27694546
TI  - Letter to the editor: Accurate cell capacitance determination from a single
      voltage step: a reminder to avoid unnecessary pitfalls.

PMID- 27694547
TI  - Relationship between illness-related worries and social dignity in patients with
      heart failure.
AB  - BACKGROUND: Heart failure is a major growing problem and affects not only
      patients but also their families and community networks and reduces the
      functional capacity of patients and impairs their social life. RESEARCH
      QUESTIONS: This study was conducted to investigate relationship between illness
      related worries and social dignity in patients with heart failure. DESIGN: The
      study had a descriptive-analytic design, and data collection was carried out by
      means of two specific questionnaires. Participants and context: A total of 130
      inpatients from cardiac wards in hospitals affiliated with Tehran and Shahid
      Beheshti University of Medical Sciences participated. Ethical consideration: This
      study was approved by the Research Committee of Shahid Beheshti University of
      Medical Sciences. RESULTS: The highest mean score of illness-related worries was
      attributed to the dimension of patient's worry of physical-mental complications,
      and the least mean score was related to the dimension of the worry about the
      future of disease. The highest mean score of social dignity was associated with
      the dimension of social communication and support, and the least is attributed to
      the dimension of burden to others (economic). Pearson's statistical test showed a
      significant correlation (r = 0.455, p < 0.05) between the score of illness
      related worries and social dignity. DISCUSSION: As the result of this study
      showed that reducing illness-related worries in patients with heart failure can
      improve their social dignity, using strategies to decrease worries and promote
      social dignity in these patients is recommended. CONCLUSION: This study affirms
      the importance of careful evaluation of individual patients to determine their
      needs related to dignity. We hope these results will help to promote actions by
      patient-care staff that honor and support patient dignity, resulting in benefits
      to patients and developing the quality of care based on human rights.

PMID- 27694545
TI  - Potential vectors of equine arboviruses in the UK.
AB  - There is growing concern about the increasing risk of disease outbreaks caused by
      arthropod-borne viruses (arboviruses) in both human beings and animals. There are
      several mosquito-borne viral diseases that cause varying levels of morbidity and
      mortality in horses and that can have substantial welfare and economic
      ramifications. While none has been recorded in the UK, vector species for some of
      these viruses are present, suggesting that UK equines may be at risk. The authors
      undertook, therefore, the first study of mosquito species on equine premises in
      the UK. Mosquito magnet traps and red-box traps were used to sample adults, and
      larvae were collected from water sources such as tyres, buckets, ditches and
      pools. Several species that are known to be capable of transmitting important
      equine infectious arboviruses were trapped. The most abundant, with a maximum
      catch of 173 in 72 hours, was Ochlerotatus detritus, a competent vector of some
      flaviviruses; the highest densities were found near saltmarsh habitats. The most
      widespread species, recorded at >75 per cent of sites, was Culiseta annulata.
      This study demonstrates that potential mosquito vectors of arboviruses, including
      those known to be capable of infecting horses, are present and may be abundant on
      equine premises in the UK.

PMID- 27694548
TI  - Ethical competence: An integrative review.
AB  - BACKGROUND: Ethics, being a fundamental component of nursing practice, must be
      integrated in the nursing education curriculum. Even though different bodies are
      promoting ethics and nursing researchers have already carried out work as regards
      this concept, it still remains difficult to clearly identify the components of
      this competence. OBJECTIVE: This integrative review intends to clarify this point
      in addition to better defining ethical competence in the context of nursing
      practice. METHOD: An integrative review was carried out, for the 2009-2014
      period, in the CINAHL, MEDLINE, and EMBASE databases and in the journal Nursing
      Ethics. The keywords nursing ethics or ethical competence were used in order to
      make sure to widely encompass the concept of "ethical competence" in the case of
      a university curriculum in nursing. In the end, 89 articles were selected.
      Ethical consideration: We have respected the ethical requirements required
      regarding the sources and authorship. There is no conflict of interest in this
      literature review. RESULTS: Ethical sensitivity, Ethical knowledge, Ethical
      reflection, Ethical decision-making, Ethical action, and Ethical behavior are the
      most frequently used terms with regard to ethical competence in nursing. They
      were then defined so as to better ascertain the possible components of ethical
      competence in nursing. CONCLUSION: Even though ethical competence represents a
      sine qua non competence in nursing practice, no consensus can be found in
      literature with respect to its definition. The identification of its components
      and their relationships resulting from this integrative review adds to the
      clarification of its definition. It paves the way for other studies that will
      contribute to a better understanding of its development, especially among nursing
      students and practicing nurses, as well as the factors that may exert an
      influence. More adapted education strategies can thus be put forward to support
      its development.

PMID- 27694549
TI  - Impacts of Socratic questioning on moral reasoning of nursing students.
AB  - BACKGROUND: Nurses are often faced with complex situations that made them to make
      ethical decisions; and to make such decisions, they need to possess the power of
      moral reasoning. Studies in Iran show that the majority of nursing students lack
      proper ethical development. Socratic teaching is a student-centered method which
      is strongly opposed to the lecturing method. OBJECTIVES: This study was conducted
      to evaluate the impacts of Socratic questioning on the moral reasoning of the
      nursing students. RESEARCH DESIGN: In a quasi-experimental study, Crisham's
      Nursing Dilemma Test was used to evaluate the results of three groups before,
      immediately after, and 2 months after intervention. The data were analyzed using
      the SPSS statistical software (v 15). Participants and research context: Through
      random allocation, 103 nursing students were divided into three groups. In
      experiment group 1 (37 students), intervention consisted of Socratic questioning
      based sessions on ethics and how to deal with moral dilemmas; experiment group 2
      (33 students) attended a 4-h workshop; and the control group (33 students) was
      not subject to any interventions. Signed informed consent forms: This research
      was approved by the Ethics Committee of the University. All the participants
      signed written informed consents. FINDINGS: There were significant differences
      between experiment group 1 and experiment group 2's pre-test and post-test scores
      on moral reasoning (p <= 0.001, p <= 0.001), nursing principled thinking (p <=
      0.001, p <= 0.001), and practical considerations (p <= 0.001, p <= 0.031).
      DISCUSSION: Both the teaching approaches improved the subjects' moral reasoning;
      however, Socratic questioning proved more effective than lecturing. Compared to
      other similar studies in Iran and other countries, the students had inadequate
      moral reasoning competence. CONCLUSION: This study confirms the need for the
      development of an efficient course on ethics in the nursing curriculum. Also, it
      appears that Socratic questioning is an effective method to teach nursing ethics
      and develop nursing students' competence of moral reasoning.

PMID- 27694550
TI  - New Fathers' Perinatal Depression and Anxiety-Treatment Options: An Integrative
      Review.
AB  - More than 10% of fathers experience depression and anxiety during the perinatal
      period, but paternal perinatal depression (PPND) and anxiety have received less
      attention than maternal perinatal mental health problems. Few mainstream
      treatment options are available for men with PPND and anxiety. The aim of this
      literature review was to summarize the current understanding of PPND and the
      treatment programs specifically designed for fathers with perinatal depression.
      Eight electronic databases were searched using a predefined strategy, and
      reference lists were also hand searched. PPND and anxiety were identified to have
      a negative impact on family relationships, as well as the health of mothers and
      children. Evidence suggests a lack of support and tailored treatment options for
      men having trouble adjusting to the transition to fatherhood. Of the limited
      options available, cognitive behavioral therapy, group work, and blended delivery
      programs, including e-support approaches appear to be most effective in helping
      fathers with perinatal depression and anxiety. The review findings have important
      implications for the understanding of PPND and anxiety. Future research is needed
      to address the adoption of father-inclusive and father-specific models of care to
      encourage fathers' help-seeking behavior. Inclusion of male-specific requirements
      into support and treatment options can improve the ability of services to engage
      new fathers. Psychotherapeutic intervention could assist to address the cognitive
      differences and dissonance for men adjusting to the role of father, including
      male identity and role expectations.

PMID- 27694551
TI  - Impact of Marital Status on Tumor Stage at Diagnosis and on Survival in Male
      Breast Cancer.
AB  - The effect of marital status (MS) on survival varies according to cancer type and
      gender. There has been no report on the impact of MS on survival in male breast
      cancer (MBC). This study aims to determine the influence of MS on tumor stage at
      diagnosis and survival in MBC. Men with MBC >=18 years of age in the SEER
      database from 1990 to 2011 were included in the study. MS was classified as
      married and unmarried (including single, divorced, separated, widowed). Kaplan
      Meier method was used to estimate the 5-year cancer-specific survival.
      Multivariate regression analyses were done to determine the effect of MS on
      presence of Stage IV disease at diagnosis and on cancer-specific mortality. The
      study included 3,761 men; 2,647 (70.4%) were married. Unmarried men were more
      often diagnosed with Stage IV MBC compared with married (10.7% vs. 5.5%, p <
      .001). Unmarried men (compared with married) were significantly less likely to
      undergo surgery (92.4% vs. 96.7%, p < .001). Overall unmarried males with Stages
      II, III, and IV MBC have significantly worse 5-year cancer-specific survival
      compared with married. On multivariate analysis, being unmarried was associated
      with increased hazard of death (HR = 1.43, p < .001) and increased likelihood of
      Stage IV disease at diagnosis ( OR = 1.96, p < .001). Unmarried males with breast
      cancer are at greater risk for Stage IV disease at diagnosis and poorer outcomes
      compared with married males.

PMID- 27694552
TI  - Canadian Men's Perspectives of Depression: Awareness and Intention to Seek Help.
AB  - It is often presumed that men are generally unaware of depression being a serious
      health issue and are unlikely to seek professional help if they became depressed.
      To test this presumption, Canadian men's ( N = 452) perspectives regarding
      awareness of depression and likelihood of seeking help for depression were
      solicited. While 78.7% of respondents recognized depression as a significant
      health issue for men, only 58.5% felt fairly or very well informed about
      depression. In terms of help-seeking intentions, 82.6% of respondents indicated
      that they probably or definitely would seek professional help if depressed.
      Contrary to popular depictions, the findings suggest that Canadian men are indeed
      aware of the seriousness of depression as a health issue, yet many are poorly
      informed about it. Furthermore, most men are well intentioned when it comes to
      seeking help if they became depressed. The findings imply that greater efforts
      are required to improve men's understanding of depression (symptoms, triggers,
      approaches to care), which may help translate intentions to seek help into
      concrete action.

PMID- 27694554
TI  - A Content Analysis of YouTubeTM Videos Related to Prostate Cancer.
AB  - In the United States, prostate cancer is the most common type of cancer in men
      after skin cancer. There is a paucity of research devoted to the types of
      prostate cancer information available on social media outlets. YouTubeTM is a
      widely used video sharing website, which is emerging as commonplace for
      information related to health. The purpose of this study was to describe the most
      widely viewed YouTubeTM videos related to prostate cancer. The 100 videos were
      watched a total of 50,278,770 times. The majority of videos were uploaded by
      consumers (45.0%) and medical or government professionals (30%). The purpose of
      most videos (78.0%) was to provide information, followed by discussions of
      prostate cancer treatment (51%) and prostate-specific antigen testing and routine
      screening (26%). All videos uploaded by medical and government professionals and
      93.8% of videos uploaded by news sources provided information compared with about
      two thirds of consumer and less than one half of commercial and advertisement
      videos ( p < .001). As society becomes increasingly technology-based, there is a
      need to help consumers acquire knowledge and skills to identify credible
      information to help inform their decisions.

PMID- 27694553
TI  - Subgrouping High School Students for Substance Abuse-Related Behaviors: A Latent
      Class Analysis.
AB  - The aim of the current study was to characterize the prevalence of latent groups
      in terms of smoking, hookah, and alcohol in a sample of Iranian high school
      students. In this cross-sectional study, 4,422 high school students were assessed
      in East Azerbaijan Province, Iran. Latent class analysis was applied to determine
      the subgroups and prevalence of each class using the procLCA in SAS 9.2 software.
      The prevalence of hookah smoking was the highest among the other substances and
      had the greatest abuse among males than females. Nearly 86%, 9.5%, and 4.6% of
      the participants were low risk, tobacco experimenter, and high risk,
      respectively. The odds ratio indices of membership in each class, compared with
      the first class, associated with the independent variables. A fair number of
      students, males in particular, were identified as high risk-takers. Considering
      the simultaneous incidence of multiple high-risk behaviors, interventions must
      cover multiple aspects of the issue at the same time.

PMID- 27694555
TI  - Strategies to prevent TEVAR-related spinal cord ischemia.
AB  - Spinal cord ischemia remains the Achilles' heel of thoracic and thoracoabdominal
      diseases management. Great improvements in morbidity and mortality have been
      obtained with the endovascular approach TEVAR (Thoracic Endovascular Aortic
      Repair) but this devastating complication continues to severely affect the
      quality of life, even if the primary success of the procedure -
      dissection/aneurysm exclusion - has been achieved. Several strategies to deal
      with this complication have been published in the literature over the time.
      Knowledge and technology have been evolving from identification of the risk
      factors associated with spinal cord ischemia, including lessons learned from open
      surgery, and from developments in the collateral network concept for spinal cord
      perfusion. In this comprehensive review, the authors cover several topics from
      the traditional measures comprising haemodynamic control, cerebrospinal drainage
      and neuroprotective drugs, to the staged-procedures approach, the emerging MISACE
      (minimally invasive selective segmental artery coil-embolization) and innovative
      neurologic monitoring such as NIRS (near-infrared spectroscopy) of the collateral
      network.

PMID- 27694556
TI  - Thoracic outlet syndrome affecting high-performance musicians playing bowed
      string instruments.
AB  - Thoracic outlet syndrome, a condition due to neurovascular compression in the
      upper shoulder region, can be caused by chronic repetitive activity of the upper
      extremities. Studies have linked upper extremity musculoskeletal disorders to
      high-performance musicians who play bowed string instruments such as the violin
      or viola. We report herein a case series of five elite musicians, including three
      violinists and two violaists, who developed neurogenic thoracic outlet syndrome
      following years of intense practice. Successful surgical treatment including
      first rib resection, scalenectomy, and brachial plexus neurolysis was performed
      in all patients. All patients were able to resume their musical career following
      surgical treatment. Our report represents the first description of thoracic
      outlet syndrome in high-performance bowed string instrumentalists. Clinicians
      should be aware of thoracic outlet syndrome as a differential diagnosis when
      treating string instrumentalists with upper extremity musculoskeletal ailments.

PMID- 27694557
TI  - Maternal mortality varies sevenfold across the US, report finds.

PMID- 27694558
TI  - Clinical Effects of Krachaidum ( Kaempferia parviflora): A Systematic Review.
AB  - Kaempferia parviflora (Krachaidum) is a medicinal plant in the family
      Zingiberaceae. Its rhizome has been used as folk medicine for many centuries. A
      number of pharmacological studies of Krachaidum had claimed benefits for various
      ailments. Therefore, this study aimed to systematically search and summarize the
      clinical evidences of Krachaidum in all identified indications. Of 683 records
      identified, 7 studies were included. From current clinical trials, Krachaidum
      showed positive benefits but remained inconclusive since small studies were
      included. Even though results found that Krachaidum significantly increased hand
      grip strength and enhanced sexual erotic stimuli, these were based on only 2
      studies and 1 study, respectively. With regard to harmful effects, we found no
      adverse events reported even when Krachaidum 1.35 g/day was used. Therefore,
      future studies of Krachaidum are needed with regards to both safety and efficacy
      outcomes.

PMID- 27694559
TI  - Effects of Singing Bowl Sound Meditation on Mood, Tension, and Well-being: An
      Observational Study.
AB  - Poor mood and elevated anxiety are linked to increased incidence of disease. This
      study examined the effects of sound meditation, specifically Tibetan singing bowl
      meditation, on mood, anxiety, pain, and spiritual well-being. Sixty-two women and
      men (mean age 49.7 years) participated. As compared with pre-meditation,
      following the sound meditation participants reported significantly less tension,
      anger, fatigue, and depressed mood (all Ps <.001). Additionally, participants who
      were previously naive to this type of meditation experienced a significantly
      greater reduction in tension compared with participants experienced in this
      meditation ( P < .001). Feeling of spiritual well-being significantly increased
      across all participants ( P < .001). Tibetan singing bowl meditation may be a
      feasible low-cost low technology intervention for reducing feelings of tension,
      anxiety, and depression, and increasing spiritual well-being. This meditation
      type may be especially useful in decreasing tension in individuals who have not
      previously practiced this form of meditation.

PMID- 27694560
TI  - Tribulus terrestris Extract Improves Human Sperm Parameters In Vitro.
AB  - OBJECTIVE: The object of present study was to investigate the effects of direct
      addition of Tribulus terrestris extract on human sperm parameters. DESIGN: Semen
      specimens from 40 healthy men volunteers were divided into 4 groups: one group
      received no treatment (control group) while the others were incubated with 20,
      40, and 50 ug/mL of T terrestris extract (experimental groups). Motility,
      viability, and DNA fragmentation were assessed in all groups. RESULTS: The
      incubation of human semen with 40 and 50 MUg/mL of T terrestris extract
      significantly enhanced total sperm motility, number of progressive motile
      spermatozoa, and curvilinear velocity over 60 to 120 minutes' holding time ( P <
      .05 or P < < .01). Furthermore, viability was significantly enhanced by using T
      terrestris extract ( P < .01). CONCLUSIONS: In vitro addition of the T terrestris
      extract to human sperm could affect male fertility capacity.

PMID- 27694561
TI  - Screening pregnant women in the 2015 European guideline on the management of
      Chlamydia trachomatis infections.

PMID- 27694562
TI  - Re: cervical screening in HIV-positive women in the East of England: recent CD4
      as the predictive risk factor.

PMID- 27694563
TI  - Acceptability of digital anal cancer screening in HIV-positive men who have sex
      with men attending a UK Sexual Health service.

PMID- 27694565
TI  - Correction for Berla and Pakrasi, Upregulation of Plasmid Genes during Stationary
      Phase in Synechocystis sp. Strain PCC 6803, a Cyanobacterium.

PMID- 27694566
TI  - The tale wagged by the DAG: broadening the scope of causal inference and
      explanation for epidemiology.
AB  - 'Causal inference', in 21st century epidemiology, has notably come to stand for a
      specific approach, one focused primarily on counterfactual and potential outcome
      reasoning and using particular representations, such as directed acyclic graphs
      (DAGs) and Bayesian causal nets. In this essay, we suggest that in epidemiology
      no one causal approach should drive the questions asked or delimit what counts as
      useful evidence. Robust causal inference instead comprises a complex narrative,
      created by scientists appraising, from diverse perspectives, different strands of
      evidence produced by myriad methods. DAGs can of course be useful, but should not
      alone wag the causal tale. To make our case, we first address key conceptual
      issues, after which we offer several concrete examples illustrating how the newly
      favoured methods, despite their strengths, can also: (i) limit who and what may
      be deemed a 'cause', thereby narrowing the scope of the field; and (ii) lead to
      erroneous causal inference, especially if key biological and social assumptions
      about parameters are poorly conceived, thereby potentially causing harm. As an
      alternative, we propose that the field of epidemiology consider judicious use of
      the broad and flexible framework of 'inference to the best explanation', an
      approach perhaps best developed by Peter Lipton, a philosopher of science who
      frequently employed epidemiologically relevant examples. This stance requires not
      only that we be open to being pluralists about both causation and evidence but
      also that we rise to the challenge of forging explanations that, in Lipton's
      words, aspire to 'scope, precision, mechanism, unification and simplicity'.

PMID- 27694567
TI  - Plasma metabolomics identified novel metabolites associated with risk of type 2
      diabetes in two prospective cohorts of Chinese adults.
AB  - BACKGROUND: Metabolomics studies in Caucasians have identified a number of novel
      metabolites in association with the risk of type 2 diabetes (T2D). However, few
      prospective metabolomic studies are available in Chinese populations. In the
      present study, we sought to identify novel metabolites consistently associated
      with incident T2D in two independent cohorts of Chinese adults. METHODS: We
      performed targeted metabolomics (52 metabolites) of fasting plasma samples by
      liquid chromatography-mass spectrometry in two prospective case-control studies
      nested within the Dongfeng-Tongji (DFTJ) cohort and Jiangsu Non-communicable
      Disease (JSNCD) cohort. After following for 4.61 +/- 0.15 and 7.57 +/- 1.13
      years, respectively, 1039 and 520 eligible participants developed incident T2D in
      these two cohorts, and controls were 1:1 matched with cases by age (+/- 5 years)
      and sex. Multivariate conditional logistic regression models were constructed to
      identify metabolites associated with future T2D risk in both cohorts. RESULTS: We
      identified four metabolites consistently associated with an increased risk of
      developing T2D in the two cohorts, including alanine, phenylalanine, tyrosine and
      palmitoylcarnitine. In the meta-analysis of two cohorts, the odds ratios (95%
      confidence intervals, CIs) comparing extreme quartiles were 1.79 (1.32-2.42) for
      alanine, 1.91 (1.41-2.60) for phenylalanine, 1.85 (1.37-2.48) for tyrosine and
      1.63 (1.21-2.20) for palmitoylcarnitine (all Ptrend <= 0.01). CONCLUSIONS: We
      confirmed the association of alanine, phenylalanine and tyrosine with future T2D
      risk and further identified palmitoylcarnitine as a novel metabolic marker of
      incident T2D in two prospective cohorts of Chinese adults. Our findings might
      provide new aetiological insight into the development of T2D.

PMID- 27694569
TI  - Data Resource Profile: WHO Health Equity Monitor (HEM).

PMID- 27694568
TI  - Effects of prenatal micronutrient and early food supplementation on metabolic
      status of the offspring at 4.5 years of age. The MINIMat randomized trial in
      rural Bangladesh.
AB  - BACKGROUND: Fetal nutritional insults may alter the later metabolic phenotype. We
      hypothesized that early timing of prenatal food supplementation and multiple
      micronutrient supplementation (MMS) would favourably influence childhood
      metabolic phenotype. METHODS: Pregnant women recruited 1 January to 31 December
      2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of
      either 30 mg of iron and 400 MUg of folic acid, 60 mg of iron and 400 MUg of
      folic acid, or MMS containing a daily allowance of 15 micronutrients, and
      randomized to food supplementation (608 kcal) either with early invitation (9
      weeks' gestation) or usual invitation (at 20 weeks). Their children (n = 1667)
      were followed up at 4.5 years with assessment of biomarkers of lipid and glucose
      metabolism, inflammation and oxidative stress. RESULTS: Children in the group
      with early timing of food supplementation had lower cholesterol (difference 
      0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density
      lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB
      levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation
      resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95%
      CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; 
      0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale 
      0.141 ug/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 MUg folic acid. There
      were no effects on markers of inflammation or oxidative stress. CONCLUSIONS:
      Findings suggest that in a population where malnutrition is prevalent, nutrition
      interventions during pregnancy may modify the metabolic phenotype in the young
      child that could have consequences for later chronic disease risks.

PMID- 27694570
TI  - Association between polygenic risk scores for attention-deficit hyperactivity
      disorder and educational and cognitive outcomes in the general population.
AB  - Background: Children with a diagnosis of attention-deficit hyperactivity disorder
      ADHD) have lower cognitive ability and are at risk of adverse educational
      outcomes; ADHD genetic risks have been found to predict childhood cognitive
      ability and other neurodevelopmental traits in the general population; thus
      genetic risks might plausibly also contribute to cognitive ability later in
      development and to educational underachievement. Methods: We generated ADHD
      polygenic risk scores in the Avon Longitudinal Study of Parents and Children
      participants (maximum N : 6928 children and 7280 mothers) based on the results of
      a discovery clinical sample, a genome-wide association study of 727 cases with
      ADHD diagnosis and 5081 controls. We tested if ADHD polygenic risk scores were
      associated with educational outcomes and IQ in adolescents and their mothers.
      Results: High ADHD polygenic scores in adolescents were associated with worse
      educational outcomes at Key Stage 3 [national tests conducted at age 13-14 years;
      beta = -1.4 (-2.0 to -0.8), P  = 2.3 * 10 -6 ), at General Certificate of
      Secondary Education exams at age 15-16 years (beta = -4.0 (-6.1 to -1.9), P  =
      1.8 * 10 -4 ], reduced odds of sitting Key Stage 5 examinations at age 16-18
      years [odds ratio (OR) = 0.90 (0.88 to 0.97), P  = 0.001] and lower IQ scores at
      age 15.5 [beta = -0.8 (-1.2 to -0.4), P  = 2.4 * 10 -4 ]. Moreover, maternal ADHD
      polygenic scores were associated with lower maternal educational achievement
      [beta = -0.09 (-0.10 to -0.06), P  = 0.005] and lower maternal IQ [beta = -0.6 (
      1.2 to -0.1), P  = 0.03]. Conclusions: ADHD diagnosis risk alleles impact on
      functional outcomes in two generations (mother and child) and likely have
      intergenerational environmental effects.

PMID- 27694573
TI  - Revisiting the drug interaction between tamoxifen and SSRI antidepressants.

PMID- 27694572
TI  - Perioperative and Anesthetic Considerations in Total Anomalous Pulmonary Venous
      Connection.
AB  - Total anomalous pulmonary venous connection (TAPVC) is a potentially devastating
      form of congenital heart disease in which all pulmonary blood flow returns to the
      systemic venous circulation rather than the left atrium. Anomalous pulmonary
      venous flow may be obstructed at birth, and affected infants present with severe
      cyanosis and poor cardiac output unresponsive to standard resuscitation with
      prostaglandin. Obstructed TAPVC remains one of the few indications for emergent
      neonatal cardiac surgery. This review will discuss the physiology and
      perioperative management of isolated TAPVC without associated cardiac lesions.

PMID- 27694574
TI  - Validation of a Brief Insomnia Severity Measure in Youth Clinically Referred for
      Sleep Evaluation.
AB  - Objectives: Evaluate psychometric properties of the Pediatric Insomnia Severity
      Index (PISI), a brief measure of insomnia severity. Methods: Clinically referred
      youth ( n = 462; 283 males, 179 females, mean age = 7.28 +/- 2.05 years) and
      their caregiver(s) completed sleep evaluation including the PISI, Children's
      Sleep Habits Questionnaire, and sleep disorders inventory for students. Tests of
      reliability and validity and confirmatory factor analysis (CFA) were conducted to
      assess PISI psychometric properties. Exploratory analyses were conducted to
      examine insomnia severity by insomnia diagnosis. Results: Measures of internal
      consistency for the PISI factor scores varied. CFA indicated that a two-factor
      model had optimal fit relative to a single-factor solution. Overall, convergent
      and discriminant validity of PISI factors were supported. Insomnia severity
      varied by diagnosis. Conclusions: Findings provide preliminary support for the
      reliability and validity of the PISI within a large pediatric sample and for its
      clinical utility as a brief measure of insomnia severity.

PMID- 27694571
TI  - Risk of mortality with concomitant use of tamoxifen and selective serotonin
      reuptake inhibitors: multi-database cohort study.
AB  - OBJECTIVE:  To compare differences in mortality between women concomitantly
      treated with tamoxifen and selective serotonin reuptake inhibitors (SSRIs) that
      are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) versus tamoxifen
      and other SSRIs. DESIGN:  Population based cohort study. SETTING:  Five US
      databases covering individuals enrolled in private and public health insurance
      programs from 1995 to 2013. PARTICIPANTS:  Two cohorts of women who started
      taking tamoxifen. In cohort 1, women started taking an SSRI during tamoxifen
      treatment. In cohort 2, women were already taking an SSRI when they started
      taking tamoxifen. MAIN OUTCOME MEASURES:  All cause mortality in each cohort in
      women taking SSRIs that are potent inhibitors of CYP2D6 (paroxetine, fluoxetine)
      versus other SSRIs. Propensity scores were used to match exposure groups in a
      variable ratio fashion. Results were measured separately for each cohort and
      combined hazard ratios calculated from Cox regression models across the two
      cohorts with random effects meta-analysis. RESULTS:  There were 6067 and 8465 new
      users of tamoxifen in cohorts 1 and 2, respectively. Mean age was 55. A total of
      991 and 1014 deaths occurred in cohorts 1 and 2 during a median follow-up of 2.2
      (interquartile range 0.9-4.5) and 2.0 (0.8-3.9) years, respectively. The pooled
      hazard ratio for death for potent inhibitors (rate 58.6/1000 person years)
      compared with other SSRIs (rate 57.9/1000 person years) across cohorts 1 and 2
      was 0.96 (95% confidence interval 0.88 to 1.06). Results were consistent across
      sensitivity analyses. CONCLUSION:  Concomitant use of tamoxifen and potent CYP2D6
      inhibiting SSRIs versus other SSRIs was not associated with an increased risk of
      death.

PMID- 27694576
TI  - Corrigendum.

PMID- 27694575
TI  - Barriers and outcomes of an evidence-based approach to diagnosis and management
      of chronic obstructive pulmonary disease (COPD) in Australia: a qualitative
      study.
AB  - Background: Chronic obstructive pulmonary disease (COPD) is commonly managed in
      primary care but there is poor awareness of evidence-based guidelines and the
      quality and interpretation of spirometry is suboptimal. Objectives: The aims of
      this qualitative study were to explore how an intervention involving case finding
      and management of COPD was implemented, and the extent to which the GPs and
      practice nurses (PNs) worked in partnership to diagnose and manage COPD. Methods:
      Semi-structured interviews with PNs (n = 7), GPs (n = 4) and patients (n = 26)
      who had participated in the Primary care EarLy Intervention for Copd mANagement
      (PELICAN) study. The Theoretical Domains Framework was used to guide the coding
      and analysis of the interviews with PN and GPs. The patient interviews were
      analysed thematically. Results: PNs developed technical skills and understood the
      requirements for good-quality spirometry. However, many lacked confidence in its
      interpretation and felt this was not part of their professional role. This was
      reflected in responses from the GPs. Once COPD was diagnosed, the GPs tended to
      manage the patients with the PNs less involved. This was in contrast with PNs'
      active role in managing patients with other chronic diseases such as diabetes.
      The extent to which the GPs and PNs worked in partnership to manage COPD varied.
      Conclusions: PNs improved their skills and confidence in performing spirometry.
      Beliefs about their professional role, identity and confidence influenced the
      extent to which PNs were involved in interpretation of the spirometry results and
      managing the patient in partnership with the GP.

PMID- 27694577
TI  - Morphometric covariation between palatal shape and skeletal pattern in children
      and adolescents: a cross-sectional study.
AB  - Objective: To assess shape covariation of the palate and craniofacial complex
      (CFC) in children and adolescents. Methods: Pre-treatment lateral cephalometric
      radiographs and corresponding maxillary casts of 100 children (8-10 years) and
      100 adolescents (15-20 years) were digitized. Exclusion criteria were previous
      orthodontic treatment, craniofacial syndromes, mouth breathing, finger sucking,
      crossbite, tooth agenesis, and tooth impaction. Palatal shape was described with
      239 surface and curve semilandmarks and craniofacial shape with 10 fixed
      landmarks and 117 curve semilandmarks. Procrustes superimposition and principal
      component analysis were applied for evaluation of shape variability. Shape
      covariation between palate and CFC was assessed with partial least squares
      analysis. Results: The first five principal components explained 77 per cent
      (palate) and 60 per cent (CFC) of total shape variability. The palate varied
      mainly in height (adolescent group) and width-length (both groups), whereas the
      CFC varied mainly in the vertical dimension. Significant covariation was found
      between the craniofacial and palatal components (RV coefficient: 0.27, children;
      RV: 0.23, adolescents). Variation of the CFC in the vertical and anteroposterior
      direction was mainly related to variation in the height-width and the width
      length ratio of the palate, respectively. Limitations: The use of lateral
      cephalometric radiographs eliminated the transverse dimension from the
      craniofacial shape analysis. The study was cross-sectional, so the observed
      intergroup differences should be interpreted with caution. Conclusions:
      Covariation strength and pattern were similar in children and adolescents. The
      closer a subject was to the high-angle end of the variability spectrum, the
      higher and narrower was the palate, and conversely.

PMID- 27694578
TI  - Redox-assisted regulation of Ca2+ homeostasis in the endoplasmic reticulum by
      disulfide reductase ERdj5.
AB  - Calcium ion (Ca2+) is an important second messenger that regulates numerous
      cellular functions. Intracellular Ca2+ concentration ([Ca2+]i) is strictly
      controlled by Ca2+ channels and pumps on the endoplasmic reticulum (ER) and
      plasma membranes. The ER calcium pump, sarco/endoplasmic reticulum calcium ATPase
      (SERCA), imports Ca2+ from the cytosol into the ER in an ATPase activity
      dependent manner. The activity of SERCA2b, the ubiquitous isoform of SERCA, is
      negatively regulated by disulfide bond formation between two luminal cysteines.
      Here, we show that ERdj5, a mammalian ER disulfide reductase, which we reported
      to be involved in the ER-associated degradation of misfolded proteins, activates
      the pump function of SERCA2b by reducing its luminal disulfide bond. Notably,
      ERdj5 activated SERCA2b at a lower ER luminal [Ca2+] ([Ca2+]ER), whereas a higher
      [Ca2+]ER induced ERdj5 to form oligomers that were no longer able to interact
      with the pump, suggesting [Ca2+]ER-dependent regulation. Binding Ig protein, an
      ER-resident molecular chaperone, exerted a regulatory role in the oligomerization
      by binding to the J domain of ERdj5. These results identify ERdj5 as one of the
      master regulators of ER calcium homeostasis and thus shed light on the importance
      of cross talk among redox, Ca2+, and protein homeostasis in the ER.

PMID- 27694581
TI  - Important progress.

PMID- 27694580
TI  - Combining natural language processing and network analysis to examine how
      advocacy organizations stimulate conversation on social media.
AB  - Social media sites are rapidly becoming one of the most important forums for
      public deliberation about advocacy issues. However, social scientists have not
      explained why some advocacy organizations produce social media messages that
      inspire far-ranging conversation among social media users, whereas the vast
      majority of them receive little or no attention. I argue that advocacy
      organizations are more likely to inspire comments from new social media audiences
      if they create "cultural bridges," or produce messages that combine
      conversational themes within an advocacy field that are seldom discussed
      together. I use natural language processing, network analysis, and a social media
      application to analyze how cultural bridges shaped public discourse about autism
      spectrum disorders on Facebook over the course of 1.5 years, controlling for
      various characteristics of advocacy organizations, their social media audiences,
      and the broader social context in which they interact. I show that organizations
      that create substantial cultural bridges provoke 2.52 times more comments about
      their messages from new social media users than those that do not, controlling
      for these factors. This study thus offers a theory of cultural messaging and
      public deliberation and computational techniques for text analysis and
      application-based survey research.

PMID- 27694582
TI  - Management of sports injuries of the foot and ankle: An update.
AB  - Injuries to the foot in athletes are often subtle and can lead to a substantial
      loss of function if not diagnosed and treated appropriately. For these injuries
      in general, even after a diagnosis is made, treatment options are controversial
      and become even more so in high level athletes where limiting the time away from
      training and competition is a significant consideration. In this review, we cover
      some of the common and important sporting injuries affecting the foot including
      updates on their management and outcomes. Cite this article: Bone Joint J 2016;98
      B:1299-1311.

PMID- 27694579
TI  - Activation of Notch1 synergizes with multiple pathways in promoting castration
      resistant prostate cancer.
AB  - Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of
      prostate cancer-specific mortality. Defining new mechanisms that can predict
      recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized
      high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or
      low/intermediate-risk prostate cancer, express high levels of nuclear Notch
      homolog 1, translocation-associated (Notch1) receptor intracellular domain.
      Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered
      in early disease to promote the development of prostate adenocarcinoma. These
      tumors display features of epithelial-to-mesenchymal transition, a cellular state
      associated with increased tumor aggressiveness. Consistent with its activation in
      clinical CRPC, tumors driven by Notch1 intracellular domain in combination with
      multiple pathways altered in prostate cancer are metastatic and resistant to
      androgen deprivation. Our study provides functional evidence that the Notch1
      signaling axis synergizes with alternative pathways in promoting metastatic CRPC
      and may represent a new therapeutic target for advanced prostate cancer.

PMID- 27694583
TI  - The plantaris tendon: a narrative review focusing on anatomical features and
      clinical importance.
AB  - In recent years, the plantaris tendon has been implicated in the development of
      chronic painful mid-portion Achilles tendinopathy. In some cases, a thickened
      plantaris tendon is closely associated with the Achilles tendon, and surgical
      excision of the plantaris tendon has been reported to be curative in patients who
      have not derived benefit following conservative treatment and surgical
      interventions. The aim of this review is to outline the basic aspects of, and the
      recent research findings, related to the plantaris tendon, covering anatomical
      and clinical studies including those dealing with histology, imaging and
      treatment. Cite this article: Bone Joint J 2016;98-B:1312-19.

PMID- 27694584
TI  - Resident education in orthopaedic trauma: the future role of competency-based
      medical education.
AB  - As residency training programmes around the globe move towards competency-based
      medical education (CBME), there is a need to review current teaching and
      assessment practices as they relate to education in orthopaedic trauma.
      Assessment is the cornerstone of CBME, as it not only helps to determine when a
      trainee is fit to practice independently, but it also provides feedback on
      performance and guides the development of competence. Although a standardised
      core knowledge base for trauma care has been developed by the leading national
      accreditation bodies and international agencies that teach and perform research
      in orthopaedic trauma, educators have not yet established optimal methods for
      assessing trainees' performance in managing orthopaedic trauma patients. This
      review describes the existing knowledge from the literature on assessment in
      orthopaedic trauma and highlights initiatives that have recently been undertaken
      towards CBME in the United Kingdom, Canada and the United States. In order to
      support a CBME approach, programmes need to improve the frequency and quality of
      assessments and improve on current formative and summative feedback techniques in
      order to enhance resident education in orthopaedic trauma. Cite this article:
      Bone Joint J 2016;98-B:1320-5.

PMID- 27694585
TI  - A pre-operative predictive score for the outcome of eccentric rotational
      acetabular osteotomy in the treatment of acetabular dysplasia and early
      osteoarthritis of the hip in adults.
AB  - AIMS: The influence of identifiable pre-operative factors on the outcome of
      eccentric rotational acetabular osteotomy (ERAO) is unknown. We aimed to
      determine the factors that might influence the outcome, in order to develop a
      scoring system for predicting the prognosis for patients undergoing this
      procedure. PATIENTS AND METHODS: We reviewed 700 consecutive ERAOs in 54 men and
      646 women with symptomatic acetabular dysplasia or early onset osteoarthritis
      (OA) of the hip, which were undertaken between September 1989 and March 2013. The
      patients' pre-operative background, clinical and radiological findings were
      examined retrospectively. Multivariate Cox regression analysis was performed
      using the time from the day of surgery to a conversion to total hip arthroplasty
      (THA) as an endpoint. A risk score was calculated to predict the prognosis for
      conversion to THA, and its predictive capacity was investigated. RESULTS: The
      congruity of the hip, age, the pre-operative minimum width of the joint space and
      range of abduction were identified as factors predicting conversion to THA. For
      three groups of patients (scoring 0 to 5, 6 to 7, and 8 to 9 points), the Kaplan
      Meier event-free rates of survival at 15 years post-operatively for conversion to
      THA were 99.6%, 85.2% and 67.3%, respectively. CONCLUSION: These four pre
      operative factors are easily measured and predict the prognosis for patients
      following ERAO. They may be used for decision making when offering surgical
      treatment to patients with acetabular dysplasia and early onset osteoarthritis.
      Cite this article: Bone Joint J 2016;98-B:1326-32.

PMID- 27694586
TI  - Comparison of femoral component migration between Refobacin bone cement R and
      Palacos R + G in cemented total hip arthroplasty: A randomised controlled
      roentgen stereophotogrammetric analysis and clinical study.
AB  - AIMS: The widely used and well-proven Palacos R (a.k.a. Refobacin Palacos R) bone
      cement is no longer commercially available and was superseded by Refobacin bone
      cement R and Palacos R + G in 2005. However, the performance of these newly
      introduced bone cements have not been tested in a phased evidence-based manner,
      including roentgen stereophotogrammetric analysis (RSA). PATIENTS AND METHODS: In
      this blinded, randomised, clinical RSA study, the migration of the Stanmore
      femoral component was compared between Refobacin bone cement R and Palacos R + G
      in 62 consecutive total hip arthroplasties. The primary outcome measure was
      femoral component migration measured using RSA and secondary outcomes were Harris
      hip score (HHS), Hip disability and Osteoarthritis Outcome Score (HOOS), EuroQol
      5D (EQ-5D) and Short Form 36 (SF-36). RESULTS: Femoral component migration was
      comparable between Refobacin bone cement R and Palacos R + G during the two-year
      follow-up period with an estimated mean difference of 0.06 mm of subsidence (p =
      0.56) and 0.08 degrees  of retroversion (p = 0.82). Five hips (three Refobacin
      bone cement R and two Palacos R + G) showed non-stabilising, continuous
      migration; the femoral cement mantle in these hips, was mean 0.7 mm thicker (p =
      0.02) and there were more radiolucencies at the bone-cement interface (p = 0.004)
      in comparison to hips showing stabilising migration. Post-operative HHS was
      comparable throughout the follow-up period (p = 0.62). HOOS, EQ5D, and SF-36
      scores were also comparable (p-values > 0.05) at the two-year follow-up point.
      CONCLUSION: Refobacin bone cement R and Palacos R + G show comparable component
      migration and clinical outcome during the first two post-operative years. Hips
      showing continuous migration are at risk for early failure. However, this seems
      to be unrelated to cement type, but rather to cementing technique. Cite this
      article: Bone Joint J 2016;98-B:1333-41.

PMID- 27694587
TI  - Patient-specific instrumentation improves the accuracy of acetabular component
      placement in total hip arthroplasty.
AB  - AIMS: Accurate placement of the acetabular component during total hip
      arthroplasty (THA) is an important factor in the success of the procedure.
      However, the reported accuracy varies greatly and is dependent upon whether free
      hand or navigated techniques are used. The aim of this study was to assess the
      accuracy of an instrument system that incorporates 3D printed, patient-specific
      guides designed to optimise the placement of the acetabular component. PATIENTS
      AND METHODS: A total of 100 consecutive patients were prospectively enrolled and
      the accuracy of placement of the acetabular component was measured using post
      operative CT scans. PATIENTS AND METHODS: A total of 100 consecutive patients
      were prospectively enrolled and the accuracy of placement of the acetabular
      component was measured using post-operative CT scans. CONCLUSION: Accurate
      placement of the acetabular component can be achieved using patient-specific
      guides and is superior to free hand techniques and comparable to navigated and
      robotic techniques. Cite this article: Bone Joint J 2016;98-B:1342-6.

PMID- 27694588
TI  - The influence of cemented femoral stem choice on the incidence of revision for
      periprosthetic fracture after primary total hip arthroplasty: an analysis of
      national joint registry data.
AB  - AIMS: Periprosthetic fracture (PF) after primary total hip arthroplasty (THA) is
      an uncommon but potentially devastating complication. This study aims to
      investigate the influence of cemented stem designs on the risk of needing a
      revision for a PF. PATIENTS AND METHODS: We analysed data on 257 202 primary THAs
      with cemented stems and 390 linked first revisions for PF recorded in the
      National Joint Registry (NJR) of England, Wales and Northern Ireland to determine
      if a cemented femoral stem brand was associated with the risk of having revision
      for a PF after primary THA. All cemented femoral stem brands with more than 10
      000 primary operations recorded in the NJR were identified. The four most
      commonly used cemented femoral stems were the Exeter V40 (n = 146 409), CPT (n =
      24 300), C-Stem (n = 15 113) and Charnley (n = 20 182). We compared the revision
      risk ratios due to PF amongst the stems using a Poisson regression model
      adjusting for patient factors. Compared with the Exeter V40, the age, gender and
      ASA grade adjusted revision rate ratio was 3.89 for the cemented CPT stem (95%
      confidence interval (CI) 3.07 to 4.93), 0.89 for the C-Stem (95% CI 0.57 to 1.41)
      and 0.41 for the Charnley stem (95% CI 0.24 to 0.70). CONCLUSIONS: The
      limitations of the study include incomplete data capture, analysis of only PF
      requiring revision and that observation does not imply causality. Nevertheless,
      this study demonstrates that the choice of a cemented stem may influence the risk
      of revision for PF. Cite this article: Bone Joint J 2016;98-B:1347-54.

PMID- 27694589
TI  - The diagnostic thresholds for synovial fluid analysis in late periprosthetic
      infection of the hip depend on the duration of symptoms.
AB  - AIMS: We hypothesised that the synovial white blood cell (WBC) count in patients
      with a late periprosthetic joint infection (PJI) of the hip would depend on the
      duration of a patient's symptoms, and that the optimal diagnostic threshold would
      also depend on this period of time. PATIENTS AND METHODS: The synovial WBC count
      and percentage of polymorphonuclear cells (%PMN), and the serum CRP and ESR
      levels obtained > six weeks after primary THA were compared between 50 infected
      and 88 non-infected THAs, and in patients with symptoms for more than or less
      than two weeks. Diagnostic thresholds for the synovial WBC count were calculated
      using area under the curve calculation. RESULTS: The synovial WBC count was
      significantly higher in patients with symptoms for <= two weeks compared with
      those with symptoms for > two weeks (p = 0.03). The optimal threshold for
      diagnosing PJI for the synovial WBC count was 5750 cells/uL (sensitivity 94;
      specificity 100; PPV 100%; NPV 89%; AUC 99%) and 1556 cells/uL (sensitivity 91;
      specificity 94; PPV 87% and NPV 97%; AUC 95%), respectively. The thresholds for
      the cut-offs based on duration of symptoms improved the diagnostic performance of
      this test. CONCLUSION: This study shows that the diagnostic thresholds for
      synovial fluid analysis in late periprosthetic infection following THA may depend
      on duration of symptoms. Cite this article: Bone Joint J 2016;98-B:1355-9.

PMID- 27694590
TI  - The early outcome of kinematic versus mechanical alignment in total knee
      arthroplasty: a prospective randomised control trial.
AB  - AIMS: Our aim was to compare kinematic with mechanical alignment in total knee
      arthroplasty (TKA). PATIENTS AND METHODS: We performed a prospective blinded
      randomised controlled trial to compare the functional outcome of patients
      undergoing TKA in mechanical alignment (MA) with those in kinematic alignment
      (KA). A total of 71 patients undergoing TKA were randomised to either kinematic
      (n = 36) or mechanical alignment (n = 35). Pre- and post-operative hip-knee-ankle
      radiographs were analysed. The knee injury and osteoarthritis outcome score
      (KOOS), American Knee Society Score, Short Form-36, Euro-Qol (EQ-5D), range of
      movement (ROM), two minute walk, and timed up and go tests were assessed pre
      operatively and at six weeks, three and six months and one year post-operatively.
      RESULTS: A total of 78% of the kinematically aligned group (28 patients) and 77%
      of the mechanically aligned group (27 patients) were within 3 degrees  of their
      pre-operative plan. There were no statistically significant differences in the
      mean KOOS (difference 1.3, 95% confidence interval (CI) -9.4 to 12.1, p = 0.80),
      EQ-5D (difference 0.8, 95% CI -7.9 to 9.6, p = 0.84), ROM (difference 0.1, 95% CI
      -6.0 to 6.1, p = 0.99), two minute distance tolerance (difference 20.0, 95% CI 
      52.8 to 92.8, p = 0.58), or timed up and go (difference 0.78, 95% CI -2.3 to 3.9,
      p = 0.62) between the groups at one year. CONCLUSION: Kinematically aligned TKAs
      appear to have comparable short-term results to mechanically aligned TKAs with no
      significant differences in function one year post-operatively. Further research
      is required to see if any theoretical long-term functional benefits of kinematic
      alignment are realised or if there are any potential effects on implant survival.
      Cite this article: Bone Joint J 2016;98-B:1360-8.

PMID- 27694591
TI  - Abnormalities of gait caused by ankle arthritis are improved by ankle
      arthrodesis.
AB  - AIMS: The surgical management of ankle arthritis with tibiotalar arthrodesis is
      known to alter gait, as compared with normal ankles. The purpose of this study
      was to assess post-operative gait function with gait before arthrodesis. PATIENTS
      AND METHODS: We prospectively studied 20 patients who underwent three-dimensional
      gait analysis before and after tibiotalar arthrodesis. Cadence, step length,
      walking velocity and total support time were assessed. Kinetic parameters,
      including the moment and power of the ankle in the sagittal plane and hip power
      were also recorded. RESULTS: Significant improvement was recorded across numerous
      parameters compared with pre-operative measurements. Temporal-spatial data
      demonstrated a significant increase in step length (p = 0.003) and velocity (p =
      < 0.001). Total support time decreased for the unaffected limb (p = 0.01).
      Kinematic results demonstrated that in the affected limb, total sagittal range of
      movement did not change significantly (p = 0.1259). However, the arc of movement
      had a near congruent shift with mean maximal dorsiflexion increasing from 5
      degrees  (-17 degrees  to 16 degrees ) to 12 degrees  (5 degrees  to 18 degrees )
      (p < 0.001) and mean maximal plantarflexion decreasing from 6.8 degrees  (6
      degrees  to 21 degrees ) to 0.9 degrees  (-9 degrees  to 8 degrees ) (p = 0.003).
      Mean hip joint range of movement increased by 6 degrees  (-7 degrees  to 24
      degrees ; p = 0.003). Kinetic results demonstrated no statistically significant
      change in ankle power (p = 0.1292). However, there was an increase in ankle
      moment (p = 0.04) and hip power (p = 0.01) in the surgically treated extremity.
      Sagittal plane range of movement was not reduced after tibiotalar fusion.
      CONCLUSION: Although following tibiotalar arthrodesis the gait demonstrated never
      matched the gait shown in unaffected ankles, compared with the pre-operative
      analysis there was improvement in numerous temporal-spatial, kinematic, and
      kinetic measures. Cite this article: Bone Joint J 2016;98-B:1369-75.

PMID- 27694592
TI  - Outcomes following excision of Morton's interdigital neuroma: a prospective
      study.
AB  - AIMS: This is the first prospective study to report the pre- and post-operative
      patient reported outcomes and satisfaction scores following excision of
      interdigital Morton's neuroma. PATIENTS AND METHODS: Between May 2006 and April
      2013, we prospectively studied 99 consecutive patients (111 feet) who were to
      undergo excision of a Morton's neuroma. There were 78 women and 21 men with a
      mean age at the time of surgery of 56 years (22 to 78). Patients completed the
      Manchester-Oxford Foot Questionnaire (MOXFQ), Short Form-12 (SF-12) and a
      supplementary patient satisfaction survey three months pre-operatively and six
      months post-operatively. RESULTS: Statistically significant differences were
      found between the mean pre- and post-operative MOXFQ and the physical component
      of the SF-12 scores (p = 0.00081 and p = 0.00092 respectively). Most patients
      reported their overall satisfaction as excellent (n = 49, 49.5%) or good (n = 29,
      29.3%), but ten patients were dissatisfied, reporting poor (n = 8, 8.1%) or very
      poor (n = 2, 2.0%) results. Only 63 patients (63%) were pain-free at follow-up:
      in eight patients (8.1%), the MOXFQ score worsened. There was no statistically
      significant difference in outcome between surgery on single or multiple sites.
      However, the MOXFQ scores were significantly worse after revision surgery (p =
      0.004). CONCLUSIONS: The patient-reported outcomes after resection of a
      symptomatic Morton's neuroma are acceptable but may not be as good as earlier
      studies suggest. Surgery at several sites can be undertaken safely but caution
      should be exercised when considering revision surgery. Cite this article: Bone
      Joint J 2016;98-B:1376-81.

PMID- 27694593
TI  - Outcomes following femoral lengthening: An initial comparison of the Precice
      intramedullary lengthening nail and the LRS external fixator monorail system.
AB  - AIMS: Patients undergoing femoral lengthening by external fixation tolerate
      treatment less well when compared to tibial lengthening. Lengthening of the femur
      with an intramedullary device may have advantages. PATIENTS AND METHODS: We
      reviewed all cases of simple femoral lengthening performed at our unit from 2009
      to 2014. Cases of nonunions, concurrent deformities, congenital limb deficiencies
      and lengthening with an unstable hip were excluded, leaving 33 cases (in 22
      patients; 11 patients had bilateral procedures) for review. Healing index,
      implant tolerance and complications were compared. RESULTS: In 20 cases (15
      patients) the Precice lengthening nail was used and in 13 cases (seven patients)
      the LRS external fixator system. The desired length was achieved in all cases in
      the Precice group and in 12 of 13 cases in the LRS group. The mean healing index
      was 31.3 days/cm in the Precice and 47.1 days/cm in the LRS group (p < 0.001).
      This was associated with an earlier ability to bear full weight without aids in
      the Precice group. There were more complications with LRS lengthening, including
      pin site infections and regenerate deformity. Implant tolerance and the patients'
      perception of the cosmetic result were better with the Precice treatment.
      CONCLUSION: Femoral lengthening with the Precice femoral nail achieved excellent
      functional results with fewer complications and greater patient satisfaction when
      compared with the LRS system in our patients. Cite this article: Bone Joint J
      2016;98-B:1382-8.

PMID- 27694594
TI  - Muscle regeneration following repair of the rotator cuff.
AB  - AIMS: The aim of this study was to analyse human muscle tissue before and after
      rotator cuff repair to look for evidence of regeneration, and to characterise the
      changes seen in the type of muscle fibre. PATIENTS AND METHODS: Patients were
      assessed pre-operatively and one year post-operatively using the Oxford Shoulder
      Score (OSS) and MRI. The cross-sectional area and distribution of the type of
      muscle fibre were assessed on biopsies, which were taken at surgery and one year
      post-operatively. Paired samples from eight patients were analysed. There were
      three men and five women with a mean age of 63 years (50 to 73). RESULTS: All but
      one patient showed improvement in OSS (p = 0.004). The mean increase in the cross
      sectional area of the muscle was 1220 MUm2 (-801 to 3712; p = 0.03). There was a
      reduction of type 2a fibres (p = 0.02). A clear relationship could not be seen
      between the MRI findings and the histological appearances. CONCLUSION: This is
      the first study to provide evidence that atrophy of the supraspinatus muscle is
      reversible. Changes in the types of fibre are discussed. MRI assessment of muscle
      atrophy may not be fully representative of myofibre atrophy. Cite this article:
      Bone Joint J 2016;98-B:1389-94.

PMID- 27694595
TI  - Anatomy of the terminal branch of the posterior circumflex humeral artery:
      relevance to the deltopectoral approach to the shoulder.
AB  - AIMS: Despite the expansion of arthroscopic surgery of the shoulder, the open
      deltopectoral approach is increasingly used for the fixation of fractures and
      arthroplasty of the shoulder. The anatomy of the terminal branches of the
      posterior circumflex humeral artery (PCHA) has not been described before. We
      undertook an investigation to correct this omission. PATIENTS AND METHODS: The
      vascular anatomy encountered during 100 consecutive elective deltopectoral
      approaches was recorded, and the common variants of the terminal branches of the
      PCHA are described. RESULTS: In total, 92 patients (92%) had a terminal branch
      that crossed the space between the deltoid and the proximal humerus and which was
      therefore vulnerable to tearing or avulsion during the insertion of the blade of
      a retractor during the deltopectoral approach to the shoulder. In 75 patients
      (75%) there was a single vessel, in 16 (16%) a double vessel and in one a triple
      vessel. CONCLUSION: The relationship of these vessels to the landmark of the
      tendon of the insertion of pectoralis major into the proximal humerus is
      described. Damage to these previously undocumented branches can cause persistent
      bleeding leading to prolonged surgery and post-operative haematoma and infection,
      as well as poor visualisation during the procedure. Cite this article: Bone Joint
      J 2016;98-B:1395-8.

PMID- 27694596
TI  - Prospective randomised comparison of ring versus rail fixator in infected gap
      nonunion of tibia treated with distraction osteogenesis.
AB  - AIMS: This is a prospective randomised study which compares the radiological and
      functional outcomes of ring and rail fixators in patients with an infected gap (>
      3 cm) nonunion of the tibia. PATIENTS AND METHODS: Between May 2008 and February
      2013, 70 patients were treated at our Institute for a posttraumatic
      osseocutaneous defect of the tibia measuring at least 3 cm. These were randomised
      into two groups of 35 patients using the lottery method. Group I patients were
      treated with a ring fixator and group II patients with a rail fixator. The mean
      age was 33.2 years (18 to 64) in group I and 29.3 years (18 to 65) in group II.
      The mean bone gap was 5.84 cm in group I and 5.78 cm in group II. The mean
      followup was 33.8 months in group I and 32.6 months in group II. Bone and
      functional results were assessed using the classification of the Association for
      the Study and Application of the Method of Ilizarov (ASAMI). Functional results
      were also assessed at six months using the short musculoskeletal functional
      assessment (SMFA) score. RESULTS: The bone result was excellent, good, fair and
      poor in 21, 12, 0 and 2 in group I; and 14, 15, 3, and 3 in group II,
      respectively. The functional results were excellent, good, fair, poor and failure
      in 16, 17, 1, 0 and 1 in group I; and 22, 10, 0, 3 and 0 in group II,
      respectively. Both fixator systems achieved comparable rates of union and
      functional outcomes. The rate of deep pintract infection was significantly higher
      in the rail fixator group but patients found it more comfortable. CONCLUSION: We
      recommend the use of a ring fixator in patients with a bone gap of more than 6
      cm. Patients with a bone gap up to 6 cm can be managed with either a ring or rail
      fixator. Cite this article: Bone Joint J 2016;98B:1399-1405.

PMID- 27694597
TI  - Data errors in the National Hip Fracture Database: a local validation study.
AB  - AIMS: We present an audit comparing our level I major trauma centre's data for a
      cohort of patients with hip fractures in the National Hip Fracture Database
      (NHFD) with locally held data on these patients. PATIENTS AND METHODS: A total of
      2036 records for episodes between July 2009 and June 2014 were reviewed. RESULTS:
      The demographics of nine patients were recorded incorrectly. The rate of
      incorrect data in operation codes was most significant with overall accuracy of
      0.637 (95% CI 0.615 to 0.658). The sensitivity of NHFD coding ranged from 0.250
      to 1.000 and the specificity 0.879 to 0.999. The recording of cementation had a
      sensitivity of 0.932 and specificity of 0.713. The recording of total hip
      arthroplasty had a sensitivity of 0.739 and specificity of 0.983. The overall
      accuracy of mortality data was 0.942 (95% CI 0.931 to 0.952), with sensitivity of
      0.967 and specificity of 0.419. CONCLUSION: This paper highlights the need for
      local audit of the integrity of data uploaded to the NHFD. Cite this article:
      Bone Joint J 2016;98-B:1406-9.

PMID- 27694598
TI  - The long-term outcome of childhood supracondylar humeral fractures: A population
      based follow up study with a minimum follow up of ten years and normal matched
      comparisons.
AB  - AIMS: We present the clinical and radiographic outcome of 81 children with
      Gartland type I to III supracondylar humeral fractures at a minimum follow-up of
      ten years (mean 12.1 years; 10.3 to 16.1) following injury. PATIENTS AND METHODS:
      The clinical and functional outcomes are compared with normal age- and gender
      matched individuals. The population-based study setting was first identified from
      the institutional registries; the rate of participation was 76%. Controls were
      randomly selected from Finnish National Population Registry. RESULTS: According
      to Flynn's criteria, most fractures (75.3%) resulted in a satisfactory ("good or
      excellent") outcome. Satisfactory recovery was achieved in 75.0% of type I
      fractures treated by closed splinting (p = 0.013). Type II fractures were
      associated with both satisfactory (57.7%) and unsatisfactory (42.3%) results,
      regardless of the type of treatment, although the numbers were small in the sub
      groups. Most type III fractures were treated operatively, and most (76%) had a
      satisfactory outcome according to Flynn's criteria (p = 0.015). Compared with
      none among the normal subjects, flexion of the elbow was reduced by > 10 degrees 
      at long-term follow-up in 20 cases (24.7%, p < 0.001) and 9 (11.1%) had a reduced
      flexion of > 15 degrees  (p = 0.004). In patients who had sustained a type III
      fracture, the carrying angle was decreased by 35.7% (from 9.8 degrees  to 6.3
      degrees ; p = 0.048). All patients achieved an excellent Mayo Elbow Performance
      Score (mean 96.4 points). CONCLUSION: The long-term outcome of extension-type
      supracondylar humeral fractures is generally good, but not exclusively benign,
      with the potential for long-term pain and ulnar nerve sensitivity, and a decrease
      in grip strength and range of movement in type II and type III fractures. Bony
      remodelling cannot be relied upon to correct any residual deformity. In
      particular, type II fractures have impaired long-term recovery and justify
      individual consideration in their treatment. Cite this article: Bone Joint J
      2016;98-B:1410-17.

PMID- 27694599
TI  - Can a urine dipstick test be used to assess smoking status in patients undergoing
      planned orthopaedic surgery? a prospective cohort study.
AB  - AIMS: Smoking is associated with post-operative complications but smokers often
      under-report the amount they smoke. Our objective was to determine whether a
      urine dipstick test could be used as a substitute for quantitative cotinine
      assays to determine smoking status in patients. PATIENTS AND METHODS: Between
      September 2013 and July 2014 we conducted a prospective cohort study in which 127
      consecutive patients undergoing a planned foot and ankle arthrodesis or osteotomy
      were included. Patients self-reported their smoking status and were classified
      as: 'never smoked' (61 patients), 'ex-smoker' (46 patients), or 'current smoker'
      (20 patients). Urine samples were analysed with cotinine assays and cotinine
      dipstick tests. RESULTS: There was a high degree of concordance between dipstick
      and assay results (Kappa coefficient = 0.842, p < 0.001). Compared with the
      quantitative assay, the dipstick had a sensitivity of 88.9% and a specificity of
      97.3%. Patients claiming to have stopped smoking just before surgery had the
      highest rate of disagreement between reported smoking status and urine testing.
      CONCLUSION: Urine cotinine dipstick testing is cheap, fast, reliable, and easy to
      use. It may be used in place of a quantitative assay as a screening tool for
      detecting patients who may be smoking. A positive test may be used as a trigger
      for further assessment and counselling. Cite this article: Bone Joint J 2016;98
      B:1418-24.

PMID- 27694600
TI  - Doctors in space (ships): biomedical uncertainties and medical authority in
      imagined futures.
AB  - There has been considerable interest in images of medicine in popular science
      fiction and in representations of doctors in television fiction. Surprisingly
      little attention has been paid to doctors administering space medicine in science
      fiction. This article redresses this gap. We analyse the evolving figure of 'the
      doctor' in different popular science fiction television series. Building upon
      debates within Medical Sociology, Cultural Studies and Media Studies we argue
      that the figure of 'the doctor' is discursively deployed to act as the moral
      compass at the centre of the programme narrative. Our analysis highlights that
      the qualities, norms and ethics represented by doctors in space (ships) are
      intertwined with issues of gender equality, speciesism and posthuman ethics. We
      explore the signifying practices and political articulations that are played out
      through these cultural imaginaries. For example, the ways in which 'the simple
      country doctor' is deployed to help establish hegemonic formations concerning
      potentially destabilising technoscientific futures involving alternative
      sexualities, or military dystopia. Doctors mostly function to provide the ethical
      point of narrative stability within a world in flux, referencing a nostalgia for
      the traditional, attentive, humanistic family physician. The science fiction
      doctor facilitates the personalisation of technological change and thus becomes a
      useful conduit through which societal fears and anxieties concerning medicine,
      bioethics and morality in a 'post 9/11' world can be expressed and explored.

PMID- 27694601
TI  - Concepts in Cancer Modeling: A Brief History.
AB  - Modeling, an experimental approach to investigate complex biological systems, has
      significantly contributed to our understanding of cancer. Although extensive
      cancer research has been conducted utilizing animal models for elucidating
      mechanisms and developing therapeutics, the concepts in a good model design and
      its application have not been well elaborated. In this review, we discuss the
      theory underlying biological modeling and the process of producing a valuable and
      relevant animal model. Several renowned examples in the history of cancer
      research will be used to illustrate how modeling can be translatable to clinical
      applications. Finally, we will also discuss how the advances in cancer genomics
      and cancer modeling will influence each other going forward. Cancer Res; 76(20);
      5921-5. (c)2016 AACR.

PMID- 27694603
TI  - Sports and Suicide.

PMID- 27694602
TI  - Finally, An Apoptosis-Targeting Therapeutic for Cancer.
AB  - Resistance to cell death represents one of the hallmarks of cancer. Various
      genetic and epigenetic changes in malignant cells afford cytoprotection in the
      face of genomic instability, oncogene activation, microenvironment stress,
      chemotherapy, targeted anticancer drugs, and even immunotherapy. Central among
      the regulators of cell life and death are Bcl-2 family proteins, with the
      founding member of the family (B-cell lymphoma/leukemia-2) discovered via its
      involvement in chromosomal translocations in lymphomas. The quest for
      therapeutics that target cell survival protein Bcl-2 represents a long road
      traveled, with many dead-ends, disappointments, and delays. Finally, a Bcl-2
      targeting medicine has gained approval as a new class of anticancer agent. Cancer
      Res; 76(20); 5914-20. (c)2016 AACR.

PMID- 27694604
TI  - Arthroscopic Iliopsoas Release: Letter to the Editor.

PMID- 27694605
TI  - Arthroscopic Iliopsoas Release: Response.

PMID- 27694606
TI  - Effectiveness of PRP in the Treatment of Tendinopathy: Letter to the Editor.

PMID- 27694607
TI  - Effectiveness of PRP in the Treatment of Tendinopathy: Response.

PMID- 27694608
TI  - Effectiveness of Platelet-Rich Plasma in the Treatment of Tendinopathy: Letter to
      the Editor.

PMID- 27694609
TI  - Effectiveness of Platelet-Rich Plasma in the Treatment of Tendinopathy: Response.

PMID- 27694610
TI  - Anatomic Anterolateral Ligament Reconstruction Leads to Overconstraint at Any
      Fixation Angle: Letter to the Editor.

PMID- 27694611
TI  - Anatomic Anterolateral Ligament Reconstruction Leads to Overconstraint at Any
      Fixation Angle: Response.

PMID- 27694612
TI  - Establishing the colitis-associated cancer progression mouse models.
AB  - Inflammatory bowel disease (IBD) has been reported as an important inducer of
      colorectal cancer (CRC). The most malignant IBD-associated CRC type has been
      highlighted as colitis-associated cancer (CAC). However, lack of CAC cases and
      difficulties of the long follow-up research have challenged researchers in
      molecular mechanism probing. Here, we established pre-CAC mouse models (dextran
      sulfate sodium [DSS] group and azoxymethane [AOM] group) and CAC mouse model
      (DSS/AOM group) to mimic human CAC development through singly or combinational
      treatment with DSS and AOM followed by disease activity index analysis. We found
      that these CAC mice showed much more severe disease phenotype, including serious
      diarrhea, body weight loss, rectal prolapse and bleeding, bloody stool, tumor
      burden, and bad survival. By detecting expression patterns of several therapeutic
      targets-Apc, p53, Kras, and TNF-alpha-in these mouse models through western blot,
      histology analysis, qRT-PCR, and ELISA methods, we found that the oncogene Kras
      expression remained unchanged, while the tumor suppressors-Apc and p53 expression
      were both significantly downregulated with malignancy progression from pre-CAC to
      CAC, and TNF-alpha level was elevated the most in CAC mice blood which is of
      potential clinical use. These data indicated the successful establishment of CAC
      development mouse models, which mimics human CAC well both in disease phenotype
      and molecular level, and highlighted the promoting role of inflammation in CAC
      progression. This useful tool will facilitate the further study in CAC molecular
      mechanism.

PMID- 27694613
TI  - Effects of tranexamic acid on coagulation indexes of patients undergoing heart
      valve replacement surgery under cardiopulmonary bypass.
AB  - This study aims to explore the effects of tranexamic acid on the coagulation
      indexes of patients undergoing heart valve replacement surgery under the
      condition of cardiopulmonary bypass (CPB). One hundred patients who conformed to
      the inclusive criteria were selected and divided into a tranexamic acid group and
      a non-tranexamic acid group. They all underwent heart valve replacement surgery
      under CPB. Patients in the tranexamic acid group were intravenously injected with
      1 g of tranexamic acid (100 mL) at the time point after anesthesia induction and
      before skin incision and at the time point after the neutralization of heparin.
      Patients in the non-tranexamic acid group were given 100 mL of normal saline at
      corresponding time points, respectively. Then the coagulation indexes of the two
      groups were analyzed. The activated blood clotting time (ACT) of the two groups
      was within normal scope before CPB, while four coagulation indexes including
      prothrombin time (PT), activated partial thromboplastin time (APTT),
      international normalized ratio (INR), and fibrinogen (FIB) had significant
      increases after surgery; the PT and INR of the tranexamic acid group had a
      remarkable decline after surgery. All the findings suggest that the application
      of tranexamic acid in heart valve replacement surgery under CPB can effectively
      reduce intraoperative and postoperative blood loss.

PMID- 27694614
TI  - Critical evaluation of challenges and future use of animals in experimentation
      for biomedical research.
AB  - Animal experiments that are conducted worldwide contribute to significant
      findings and breakthroughs in the understanding of the underlying mechanisms of
      various diseases, bringing up appropriate clinical interventions. However, their
      predictive value is often low, leading to translational failure. Problems like
      translational failure of animal studies and poorly designed animal experiments
      lead to loss of animal lives and less translatable data which affect research
      outcomes ethically and economically. Due to increasing complexities in animal
      usage with changes in public perception and stringent guidelines, it is becoming
      difficult to use animals for conducting studies. This review deals with
      challenges like poor experimental design and ethical concerns and discusses key
      concepts like sample size, statistics in experimental design, humane endpoints,
      economic assessment, species difference, housing conditions, and systematic
      reviews and meta-analyses that are often neglected. If practiced, these
      strategies can refine the procedures effectively and help translate the outcomes
      efficiently.

PMID- 27694617
TI  - An eHealth information technology platform to help the treatment of mental
      disorders.
AB  - For this project, we have used new technologies to create a new channel of
      communication between doctors and patients in the treatment of mental disorders.
      We have created a web application using an adaptable design accessible from any
      mobile device, which allows doctors to adapt their patients' therapy to real-time
      knowledge of their current condition. In turn, patients can express their mood
      state with respect to the component elements of their therapy.

PMID- 27694616
TI  - Assessing empathy and managing emotions through interactions with an affective
      avatar.
AB  - Assistive technologies can improve the quality of life of people diagnosed with
      different forms of social communication disorders. We report on the design and
      evaluation of an affective avatar aimed at engaging the user in a social
      interaction with the purpose of assisting in communication therapies. A human
      avatar taxonomy is proposed to assist the design of affective avatars aimed at
      addressing social communication disorder. The avatar was evaluated with 30
      subjects to assess how effectively it conveys the desired emotion and elicits
      empathy from the user. Results provide evidence that users become used to the
      avatar after a number of interactions, and they perceive the defined behavior as
      being logical. The users' interactions with the avatar entail affective
      reactions, including the mimic emotions that users felt, and establish a
      preliminary ground truth about prototypic empathic interactions with avatars that
      is being used to train learning algorithms to support social communication
      disorder evaluation.

PMID- 27694615
TI  - Camel whey protein improves lymphocyte function and protects against diabetes in
      the offspring of diabetic mouse dams.
AB  - The prevalence of health problems in the offspring of pregnant diabetic mothers
      has recently been verified. Therefore, the present study was designed to
      investigate the influence of dietary camel whey protein (CWP), administered as a
      supplement to streptozotocin (STZ)-induced diabetic pregnant mice, on the
      efficiency of the immune system of the offspring. Three groups of female mice (n
      = 10) were used: non-diabetic control mice, diabetic mice, and diabetic mice
      orally administered CWP during the pregnancy and lactation periods. We then
      tested the immune response of B and T cells in adult male offspring (n = 15 in
      each group) by using flow cytometry, western blotting, and ELISAs. Our data
      demonstrated that the offspring of diabetic dams exhibited several postpartum
      complications, such as significant aberrant overexpression of activating
      transcription factor-3 (ATF-3), significant elevation of the plasma levels of pro
      inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) and reactive oxygen
      species (ROS), marked decreases in the plasma levels of IL-2 and IL-7,
      significant inhibition of CCL21- and CXCL12-mediated chemotaxis of B- and T
      lymphocytes, and a marked decrease in the proliferative capacity of antigen
      stimulated B- and T-lymphocytes. Interestingly, administration of CWP to diabetic
      dams substantially restored the expression of ATF-3 and the levels of ROS, pro
      inflammatory cytokines, IL-2, and IL-7 in the offspring. Furthermore, the
      chemotaxis of B- and T-lymphocytes toward CCL21 and CXCL12 and the proliferative
      capacities of these lymphocytes were restored in the male offspring of diabetic
      mice administered CWP. Our data provide evidence of a protective role of CWP in
      decreasing the tendency of the offspring of diabetic mothers to develop diabetes
      and related complications.

PMID- 27694618
TI  - Utility of Doppler ultrasonography for predicting improvement of platelet count
      after transjugular intrahepatic portosystemic shunt.
AB  - OBJECTIVE: Portal pressure gradient (PPG) after transjugular intrahepatic
      portosystemic shunt (TIPS) <12 mmHg has been reported as the only factor
      predictive of increase in platelet count. As flow velocities measured on Doppler
      ultrasound are related to pressure gradient based on the Bernoulli equation, we
      used this parameter to predict increased platelet count after TIPS placement.
      METHODS: A total of 161 consecutive patients who underwent TIPS placement entered
      this retrospective study. The platelet count was measured before, one week after
      and one month after TIPS placement. Clinically significant thrombocytopenia was
      defined as platelet count <=100 000. Pre- and post-TIPS PPGs were measured. The
      velocity of blood flow in the proximal, mid and distal TIPS stent was measured
      using Doppler ultrasound, and the difference in the highest and lowest measured
      velocity was entitled flow velocity gradient (FVG), which was considered normal
      when <=100 cm/s. RESULTS: In 121 patients with pre-TIPS thrombocytopenia, the
      mean platelet count one week and one month after TIPS placement increased 25.7 x
      103 and 35.0 x 103 in 90 patients with PPG<=12 mmHg (P=0.028 and P=0.015), while
      there was no significant change in platelet count in patients with a PPG >12 mmHg
      (P=0.098 and P=0.075). Platelets increased significantly when FVG<= 100 cm/s
      (n=95) vs FVG >100 cm/s (n=26) one week (37.0x103 vs 11.0x103; P =  0.005 vs
      0.07) and one month after TIPS placement (17.0x103 vs 5.2x103; P =  0.01 vs
      0.21). CONCLUSION: FVG >100 cm/s is not associated with increase in post-TIPS
      platelet count. On the other hand, findings suggestive of proper TIPS function
      (FVG <=100 cm/s and PPG<= 12 mmHg) predict a significant increase in post-TIPS
      platelet count.

PMID- 27694620
TI  - Single-molecule FRET reveals the pre-initiation and initiation conformations of
      influenza virus promoter RNA.
AB  - Influenza viruses have a segmented viral RNA (vRNA) genome, which is replicated
      by the viral RNA-dependent RNA polymerase (RNAP). Replication initiates on the
      vRNA 3' terminus, producing a complementary RNA (cRNA) intermediate, which serves
      as a template for the synthesis of new vRNA. RNAP structures show the 3' terminus
      of the vRNA template in a pre-initiation state, bound on the surface of the RNAP
      rather than in the active site; no information is available on 3' cRNA binding.
      Here, we have used single-molecule Forster resonance energy transfer (smFRET) to
      probe the viral RNA conformations that occur during RNAP binding and initial
      replication. We show that even in the absence of nucleotides, the RNAP-bound 3'
      termini of both vRNA and cRNA exist in two conformations, corresponding to the
      pre-initiation state and an initiation conformation in which the 3' terminus of
      the viral RNA is in the RNAP active site. Nucleotide addition stabilises the 3'
      vRNA in the active site and results in unwinding of the duplexed region of the
      promoter. Our data provide insights into the dynamic motions of RNA that occur
      during initial influenza replication and has implications for our understanding
      of the replication mechanisms of similar pathogenic viruses.

PMID- 27694619
TI  - FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the
      5'-DNA end.
AB  - The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the
      damaged DNA in the stalled replication fork. However, the means by which this DNA
      protection is accomplished have remained elusive. In the present study, we found
      that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA
      filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is
      explicitly required for the I-D complex-mediated RAD51-DNA filament
      stabilization. The RAD51 filament stabilized by the I-D complex actually protects
      the DNA end from nucleolytic degradation by an FA-associated nuclease, FAN1. This
      DNA end protection is not observed with the RAD51 mutant from FANCR patient
      cells. These results clearly answer the currently enigmatic question of how RAD51
      functions with the I-D complex to prevent genomic instability at the stalled
      replication fork.

PMID- 27694621
TI  - Single-molecule FRET studies of the cooperative and non-cooperative binding
      kinetics of the bacteriophage T4 single-stranded DNA binding protein (gp32) to
      ssDNA lattices at replication fork junctions.
AB  - Gene 32 protein (gp32) is the single-stranded (ss) DNA binding protein of the
      bacteriophage T4. It binds transiently and cooperatively to ssDNA sequences
      exposed during the DNA replication process and regulates the interactions of the
      other sub-assemblies of the replication complex during the replication cycle. We
      here use single-molecule FRET techniques to build on previous thermodynamic
      studies of gp32 binding to initiate studies of the dynamics of the isolated and
      cooperative binding of gp32 molecules within the replication complex. DNA
      primer/template (p/t) constructs are used as models to determine the effects of
      ssDNA lattice length, gp32 concentration, salt concentration, binding
      cooperativity and binding polarity at p/t junctions. Hidden Markov models (HMMs)
      and transition density plots (TDPs) are used to characterize the dynamics of the
      multi-step assembly pathway of gp32 at p/t junctions of differing polarity, and
      show that isolated gp32 molecules bind to their ssDNA targets weakly and
      dissociate quickly, while cooperatively bound dimeric or trimeric clusters of
      gp32 bind much more tightly, can 'slide' on ssDNA sequences, and exhibit binding
      dynamics that depend on p/t junction polarities. The potential relationships of
      these binding dynamics to interactions with other components of the T4 DNA
      replication complex are discussed.

PMID- 27694622
TI  - The beta-isoform of BCCIP promotes ADP release from the RAD51 presynaptic
      filament and enhances homologous DNA pairing.
AB  - Homologous recombination (HR) is a template-driven repair pathway that mends DNA
      double-stranded breaks (DSBs), and thus helps to maintain genome stability. The
      RAD51 recombinase facilitates DNA joint formation during HR, but to accomplish
      this task, RAD51 must be loaded onto the single-stranded DNA. DSS1, a candidate
      gene for split hand/split foot syndrome, provides the ability to recognize RPA
      coated ssDNA to the tumor suppressor BRCA2, which is complexed with RAD51.
      Together BRCA2-DSS1 displace RPA and load RAD51 onto the ssDNA. In addition, the
      BRCA2 interacting protein BCCIP normally colocalizes with chromatin bound BRCA2,
      and upon DSB induction, RAD51 colocalizes with BRCA2-BCCIP foci. Down-regulation
      of BCCIP reduces DSB repair and disrupts BRCA2 and RAD51 foci formation. While
      BCCIP is known to interact with BRCA2, the relationship between BCCIP and RAD51
      is not known. In this study, we investigated the biochemical role of the beta
      isoform of BCCIP in relation to the RAD51 recombinase. We demonstrate that
      BCCIPbeta binds DNA and physically and functionally interacts with RAD51 to
      stimulate its homologous DNA pairing activity. Notably, this stimulatory effect
      is not the result of RAD51 nucleoprotein filament stabilization; rather, we
      demonstrate that BCCIPbeta induces a conformational change within the RAD51
      filament that promotes release of ADP to help maintain an active presynaptic
      filament. Our findings reveal a functional role for BCCIPbeta as a RAD51
      accessory factor in HR.

PMID- 27694623
TI  - Esc2 promotes Mus81 complex-activity via its SUMO-like and DNA binding domains.
AB  - Replication across damaged DNA templates is accompanied by transient formation of
      sister chromatid junctions (SCJs). Cells lacking Esc2, an adaptor protein
      containing no known enzymatic domains, are defective in the metabolism of these
      SCJs. However, how Esc2 is involved in the metabolism of SCJs remains elusive.
      Here we show interaction between Esc2 and a structure-specific endonuclease Mus81
      Mms4 (the Mus81 complex), their involvement in the metabolism of SCJs, and the
      effects Esc2 has on the enzymatic activity of the Mus81 complex. We found that
      Esc2 specifically interacts with the Mus81 complex via its SUMO-like domains,
      stimulates enzymatic activity of the Mus81 complex in vitro, and is involved in
      the Mus81 complex-dependent resolution of SCJs in vivo Collectively, our data
      point to the possibility that the involvement of Esc2 in the metabolism of SCJs
      is, in part, via modulation of the activity of the Mus81 complex.

PMID- 27694624
TI  - Adaptive upregulation of DNA repair genes following benzo(a)pyrene diol epoxide
      protects against cell death at the expense of mutations.
AB  - A coordinated and faithful DNA damage response is of central importance for
      maintaining genomic integrity and survival. Here, we show that exposure of human
      cells to benzo(a)pyrene 9,10-diol-7,8-epoxide (BPDE), the active metabolite of
      benzo(a)pyrene (B(a)P), which represents a most important carcinogen formed
      during food preparation at high temperature, smoking and by incomplete combustion
      processes, causes a prompt and sustained upregulation of the DNA repair genes
      DDB2, XPC, XPF, XPG and POLH. Induction of these repair factors on RNA and
      protein level enhanced the removal of BPDE adducts from DNA and protected cells
      against subsequent BPDE exposure. However, through the induction of POLH the
      mutation frequency in the surviving cells was enhanced. Activation of these
      adaptive DNA repair genes was also observed upon B(a)P treatment of MCF7 cells
      and in buccal cells of human volunteers after cigarette smoking. Our data provide
      a rational basis for an adaptive response to polycyclic aromatic hydrocarbons,
      which occurs however at the expense of mutations that may drive cancer formation.

PMID- 27694626
TI  - Differential cytokine sensitivities of STAT5-dependent enhancers rely on Stat5
      autoregulation.
AB  - Cytokines utilize the transcription factor STAT5 to control cell-specific genes
      at a larger scale than universal genes, with a mechanistic explanation yet to be
      supplied. Genome-wide studies have identified putative STAT5-based mammary
      specific and universal enhancers, an opportunity to investigate mechanisms
      underlying their differential response to cytokines. We have now interrogated the
      integrity and function of both categories of regulatory elements using biological
      and genetic approaches. During lactation, STAT5 occupies mammary-specific and
      universal cytokine-responsive elements. Following lactation, prolactin levels
      decline and mammary-specific STAT5-dependent enhancers are decommissioned within
      24 h, while universal regulatory complexes remain intact. These differential
      sensitivities are linked to STAT5 concentrations and the mammary-specific Stat5
      autoregulatory enhancer. In its absence, mammary-specific enhancers, but not
      universal elements, fail to be fully established. Upon termination of lactation
      STAT5 binding to a subset of mammary enhancers is substituted by STAT3. No STAT3
      binding was observed at the most sensitive STAT5 enhancers suggesting that upon
      hormone withdrawal their chromatin becomes inaccessible. Lastly, we demonstrate
      that the mammary-enriched transcription factors GR, ELF5 and NFIB associate with
      STAT5 at sites lacking bona fide binding motifs. This study provides, for the
      first time, molecular insight into the differential sensitivities of mammary
      specific and universal cytokine-sensing enhancers.

PMID- 27694628
TI  - Sound and advanced municipal waste management: Moving from slogans and politics
      to practice and technique.

PMID- 27694627
TI  - Genetics of Skeletal Evolution in Unusually Large Mice from Gough Island.
AB  - Organisms on islands often undergo rapid morphological evolution, providing a
      platform for understanding mechanisms of phenotypic change. Many examples of
      evolution on islands involve the vertebrate skeleton. Although the genetic basis
      of skeletal variation has been studied in laboratory strains, especially in the
      house mouse Mus musculus domesticus, the genetic determinants of skeletal
      evolution in natural populations remain poorly understood. We used house mice
      living on the remote Gough Island-the largest wild house mice on record-to
      understand the genetics of rapid skeletal evolution in nature. Compared to a
      mainland reference strain from the same subspecies (WSB/EiJ), the skeleton of
      Gough Island mice is considerably larger, with notable expansions of the pelvis
      and limbs. The Gough Island mouse skeleton also displays changes in shape,
      including elongations of the skull and the proximal vs. distal elements in the
      limbs. Quantitative trait locus (QTL) mapping in a large F2 intercross between
      Gough Island mice and WSB/EiJ reveals hundreds of QTL that control skeletal
      dimensions measured at 5, 10, and/or 16 weeks of age. QTL exhibit modest, mostly
      additive effects, and Gough Island alleles are associated with larger skeletal
      size at most QTL. The QTL with the largest effects are found on a few chromosomes
      and affect suites of skeletal traits. Many of these loci also colocalize with QTL
      for body weight. The high degree of QTL colocalization is consistent with an
      important contribution of pleiotropy to skeletal evolution. Our results provide a
      rare portrait of the genetic basis of skeletal evolution in an island population
      and position the Gough Island mouse as a model system for understanding
      mechanisms of rapid evolution in nature.

PMID- 27694629
TI  - Zika virus (ZIKV) infection related with immune thrombocytopenic purpura (ITP)
      exacerbation and antinuclear antibody positivity.
AB  - A 30-year-old Colombian woman with past history of immune thrombocytopenia (ITP)
      presented to the emergency room with two days of global headache, arthralgia,
      myalgia, and low level fever and generalized erythematous rash. Platelets dropped
      to 9 * 109/L (fourth day of symptoms) without hemorrhagic manifestations but
      recovered to 30 * 109/L in 24 hours (fifth day). Dengue virus infection, as well
      as other viral infections, was ruled out. Zika virus (ZIKV) was evaluated in
      serum and urine samples by real-time reverse-transcriptase polymerase chain
      reaction (genomic regions within E protein and NS2b protein). Urine sample was
      positive and serum sample negative for ZIKV, confirming a recent ZIKV infection
      with urinary tract virus excretion at 7th day after disease onset. To our
      knowledge this is the first description of a case of severe immune
      thrombocytopenia exacerbation and antinuclear antibody positivity induced by ZIKV
      infection.

PMID- 27694630
TI  - Deciphering systemic lupus erythematosus-associated serum biomarkers reflecting
      apoptosis and disease activity.
AB  - Systemic lupus erythematosus (SLE) is a severe chronic inflammatory autoimmune
      connective tissue disease. Despite major efforts, SLE remains a poorly understood
      disease with unpredictable course, unknown etiology and complex pathogenesis.
      Apoptosis combined with deficiency in clearing apoptotic cells is an important
      etiopathogenic event in SLE, which could contribute to the increased load of
      potential autoantigen(s); however, the lack of disease-specific protein
      signatures deciphering SLE and the underlying biological processes is striking
      and represents a key limitation. In this retrospective pilot study, we explored
      the immune system as a specific sensor for disease, in order to advance our
      understanding of SLE. To this end, we determined multiplexed serum protein
      expression profiles of crude SLE serum samples, using antibody microarrays. The
      aim was to identify differential immunoprofiles, or snapshots of the immune
      response modulated by the disease, reflecting apoptosis, a key process in the
      etiology of SLE and disease activity. The results showed that multiplexed panels
      of SLE-associated serum biomarkers could be decoded, in particular reflecting
      disease activity, but potentially the apoptosis process as well. While the former
      biomarkers could display a potential future use for prognosis, the latter
      biomarkers might help shed further light on the apoptosis process taking place in
      SLE.

PMID- 27694631
TI  - Review of Naturally Occurring Intussusception in Young Children in the WHO
      African Region prior to the Era of Rotavirus Vaccine Utilization in the Expanded
      Programme of Immunization.
AB  - Rotavirus vaccines, Rotarix and RotaTeq, are increasingly being introduced in
      national immunization programmes in Africa to prevent severe dehydrating acute
      gastroenteritis. A low-level risk of intussusception has been associated with
      rotavirus vaccines. We reviewed published data on intussusception in children <2
      years of age in Africa. PubMed electronic database search was used to retrieve
      papers published on intussusception. The search was further refined to identify
      surveillance reports and case series conducted from 1980 to 2014, with at least
      25 cases. The initial search identified 34 studies, and the refined search
      yielded 16. Intussusception occurred naturally in infants 2-4 months and peaked
      around 5-8 months of age. Delayed presentation was common and required surgical
      intervention in 87% (1008 of 1158) of cases with a high CFR, 10-33.7%. In African
      children, intussusception has been reported infrequently at a young age when the
      first dose of rotavirus vaccine is administered.

PMID- 27694632
TI  - Dengue Vaccine Efficacy: Not a Zero Sum Game.

PMID- 27694634
TI  - Vaccines Against Respiratory Syncytial Virus: The Time Has Come.

PMID- 27694633
TI  - A Randomized, Controlled, Observer-Blinded Phase 1 Study of the Safety and
      Immunogenicity of a Respiratory Syncytial Virus Vaccine With or Without Alum
      Adjuvant.
AB  - BACKGROUND:  Respiratory syncytial virus (RSV) is a leading cause of childhood
      bronchiolitis and pneumonia, particularly in early infancy. Immunization of
      pregnant women could boost preexisting immune responses, providing passive
      protection to newborns through placental transfer of anti-RSV antibody. METHODS: 
      In this first-in-humans clinical trial of a purified recombinant RSV protein F
      vaccine engineered to preferentially maintain prefusion conformation (RSV-PreF),
      128 healthy men 18-44 years old were randomized to one dose of a RSV-PreF vaccine
      containing 10, 30, or 60 ug of RSV-PreF antigen, with or without alum adjuvant,
      or control, and followed for one year for safety and immunogenicity outcomes.
      RESULTS:  Injection site pain was the most common adverse event, reported by up
      to 81.3% of participants. The highest RSV neutralizing antibody responses were in
      the 30 ug RSV-PreF/alum, 60 ug RSV-PreF/alum, and 60 ug RSV-PreF/nonadjuvant
      groups. Responses were evident on day 7, and 30 days after vaccination these
      participants had RSV-A neutralizing antibody titers of >=1:512, and >70% had
      titers of 1:1024, with titers increasing by 3.2-4.9 fold. Responses remained high
      on day 60 but waned on days 180 and 360. CONCLUSIONS:  The RSV-PreF vaccine
      elicited rapid RSV neutralizing antibody responses in healthy young men, with an
      acceptable adverse event profile.

PMID- 27694636
TI  - Inverse associations between cord vitamin D and attention deficit hyperactivity
      disorder symptoms: A child cohort study.
AB  - OBJECTIVE: To examine the association between cord 25-hydroxyvitamin D2+3
      (25(OH)D) and attention deficit hyperactivity disorder symptoms in toddlers,
      using Child Behaviour Checklist for ages 1.5-5. METHOD: In a population-based
      birth cohort, a Child Behaviour Checklist for ages 1.5-5 questionnaire was
      returned from parents of 1233 infants with mean age 2.7 (standard deviation 0.6)
      years. Adjusted associations between cord 25(OH)D and Child Behaviour Checklist
      based attention deficit hyperactivity disorder problems were analysed by multiple
      regression. Results The median cord 25(OH)D was 44.1 (range: 1.5-127.1) nmol/L.
      Mean attention deficit hyperactivity disorder problem score was 2.7 (standard
      deviation 2.1). In adjusted analyses, cord 25(OH)D levels >25 nmol/L and >30
      nmol/L were associated with lower attention deficit hyperactivity disorder scores
      compared to levels ?25 nmol/L ( p = 0.035) and ?30 nmol/L ( p = 0.043),
      respectively. The adjusted odds of scoring above the 90th percentile on the Child
      Behaviour Checklist-based attention deficit hyperactivity disorder problem scale
      decreased by 11% per 10 nmol/L increase in cord 25(OH)D. CONCLUSION: An inverse
      association between cord 25(OH)D and attention deficit hyperactivity disorder
      symptoms in toddlers was found, suggesting a protective effect of prenatal
      vitamin D.

PMID- 27694635
TI  - Muramyl peptides activate innate immunity conjointly via YB1 and NOD2.
AB  - Bacterial cell wall muramyl dipeptide (MDP) and glucosaminyl-MDP (GMDP) are
      potent activators of innate immunity. Two receptor targets, NOD2 and YB1, have
      been reported; we investigated potential overlap of NOD2 and YB1 pathways.
      Separate knockdown of NOD2 and YB1 demonstrates that both contribute to GMDP
      induction of NF-kappaB expression, a marker of innate immunity, although excess
      YB1 led to induction in the absence of NOD2. YB1 and NOD2 co-migrated on sucrose
      gradient centrifugation, and GMDP addition led to the formation of higher
      molecular mass complexes containing both YB1 and NOD2. Co-immunoprecipitation
      demonstrated a direct interaction between YB1 and NOD2, a major recombinant
      fragment of NOD2 (NACHT-LRR) bound to YB1, and complex formation was stimulated
      by GMDP. We also report subcellular colocalization of NOD2 and YB1. Although YB1
      may have other binding partners in addition to NOD2, maximal innate immunity
      activation by muramyl peptides is mediated via an interaction between YB1 and
      NOD2.

PMID- 27694637
TI  - The impact of potentially traumatic events on the mental health of males who have
      served in the military: Findings from the Australian National Survey of Mental
      Health and Wellbeing.
AB  - OBJECTIVE: The study investigated the impact of potentially traumatic events on
      mental health outcomes among males who had ever served in the Australian Defence
      Force. METHOD: Data from a nationally representative household survey of
      Australian residents, the 2007 National Survey of Mental Health and Wellbeing,
      were used for this study. RESULTS: Compared with community members, Australian
      Defence Force males were significantly more likely to have experienced not only
      deployment and other war-like events but also accidents or other unexpected
      events, and trauma to someone close. For non-deployed males, Australian Defence
      Force members were at increased risk of accidents or other unexpected events
      compared to community members. After controlling for the effect of potentially
      traumatic events that were more prevalent among all Australian Defence Force
      members, the increased risk of mental disorders among Australian Defence Force
      members was no longer evident. For non-deployed males, Australian Defence Force
      and community members were at comparable risk of poor mental health outcomes. A
      significant minority of Australian Defence Force members had onset of a mental
      disorder prior to their first deployment. CONCLUSIONS: Deployment and other
      potentially traumatic events among Australian Defence Force members can help to
      explain their increased vulnerability to mental disorders compared with community
      members. Providers should routinely enquire about a range of potentially
      traumatic events among serving and ex-serving military personnel.

PMID- 27694638
TI  - Intrinsic brain abnormalities in young healthy adults with childhood trauma: A
      resting-state functional magnetic resonance imaging study of regional homogeneity
      and functional connectivity.
AB  - OBJECTIVE: Childhood trauma confers great risk for the development of multiple
      psychiatric disorders; however, the neural basis for this association is still
      unknown. The present resting-state functional magnetic resonance imaging study
      aimed to detect the effects of childhood trauma on brain function in a group of
      young healthy adults. METHODS: In total, 24 healthy individuals with childhood
      trauma and 24 age- and sex-matched adults without childhood trauma were
      recruited. Each participant underwent resting-state functional magnetic resonance
      imaging scanning. Intra-regional brain activity was evaluated by regional
      homogeneity method and compared between groups. Areas with altered regional
      homogeneity were further selected as seeds in subsequent functional connectivity
      analysis. Statistical analyses were performed by setting current depression and
      anxiety as covariates. RESULTS: Adults with childhood trauma showed decreased
      regional homogeneity in bilateral superior temporal gyrus and insula, and the
      right inferior parietal lobule, as well as increased regional homogeneity in the
      right cerebellum and left middle temporal gyrus. Regional homogeneity values in
      the left middle temporal gyrus, right insula and right cerebellum were correlated
      with childhood trauma severity. In addition, individuals with childhood trauma
      also exhibited altered default mode network, cerebellum-default mode network and
      insula-default mode network connectivity when the left middle temporal gyrus,
      right cerebellum and right insula were selected as seed area, respectively.
      CONCLUSION: The present outcomes suggest that childhood trauma is associated with
      disturbed intrinsic brain function, especially the default mode network, in
      adults even without psychiatric diagnoses, which may mediate the relationship
      between childhood trauma and psychiatric disorders in later life.

PMID- 27694639
TI  - Improving access to primary mental health care for Australian children.
AB  - OBJECTIVE: This study examines the uptake by children aged predominantly 0-11
      years of an Australian primary mental health service - the Access to Allied
      Psychological Services programme - which began in 2001. In particular, it
      considers access to, and use of, the child component of Access to Allied
      Psychological Services, the Child Mental Health Service, introduced in 2010.
      METHOD: Using routinely collected programme data from a national minimum dataset
      and regional population data, we conducted descriptive and regression analysis to
      examine programme uptake, predictors of service reach and consumer- and treatment
      based characteristics of service. RESULTS: Between 2003 and 2013, 18,631
      referrals for children were made and 75,178 sessions were scheduled via Access to
      Allied Psychological Services, over 50% of which were via the Child Mental Health
      Service in its first 3 years of operation. The rate of referrals for children to
      the Child Mental Health Service was associated with the rate of Access to Allied
      Psychological Services referrals for consumers aged 12+ years. CONCLUSIONS: The
      Child Mental Health Service has increased services provided within the Access to
      Allied Psychological Services programme for children with emotional and
      behavioural issues and their families, and is potentially filling a service gap
      in the area of prevention and early intervention for children who have
      significant levels of need but are unable to access other mental health services.
      Our findings are policy-relevant for other developed countries with a similar
      primary mental health care system that are considering means of improving service
      access by children.

PMID- 27694640
TI  - Male suicide as a gendered phenomenon: Implications for telephone crisis support.

PMID- 27694641
TI  - Aripiprazole-related hyponatremia and consequent valproic acid-related
      hyperammonemia in one patient.

PMID- 27694642
TI  - Enteral Formulas in Nutrition Support Practice: Is There a Better Choice for Your
      Patient?
AB  - Over the past few decades, the number of enteral formulas for use in
      hospitalized, critically ill, and home enteral patients has dramatically
      increased. Several enteral nutrition (EN) formula categories exist, which makes
      it challenging for clinicians to sort through the product claims and find the
      appropriate formula for the patient. Many formulas are available within each
      category, some of which may be significantly different from one another. Numerous
      systematic reviews of existing research and clinical practice guidelines evaluate
      the use of specialty formulas. This review aims to examine the differences in
      various enteral formula categories, identify applications in clinical practice,
      and evaluate the existing evidence and guideline recommendations for use of
      specific types of enteral formulas.

PMID- 27694643
TI  - Effect of sorghum consumption on health outcomes: a systematic review.
AB  - CONTEXT: Sorghum, an ancient grain originating in Africa, may have health
      protective properties that could encourage its consumption among those who do not
      traditionally consume it. OBJECTIVE: The aim of this systematic review was to
      evaluate the health effects associated with the consumption of sorghum among
      humans. DATA SOURCES: Academic databases were searched for relevant studies
      published between 1985 and November 2015. STUDY SELECTION: Nineteen studies -13
      interventional and 6 observational - were identified for inclusion. DATA
      EXTRACTION: Participant characteristics, study country, health outcomes, main
      findings, and study quality were reported. Interventional and observational
      studies were summarized separately. RESULTS: Studies were divided into those that
      investigated the effect of sorghum on chronic disease and those that investigated
      other effects of sorghum on health. There was evidence that the consumption of
      sorghum attenuated blood glucose responses and decreased the expression of
      markers of oxidative stress. Sorghum was also observed to be a suitable
      ingredient for the formulation of oral rehydration solutions and showed potential
      for use as a medical adjunct to boost immune responses in HIV-positive patients
      CONCLUSIONS: The implication is that sorghum may have attributes superior to
      those of other staple grains, indicating its potential for innovative uses in
      commercial foods. More work is required to elucidate the health effects of
      sorghum when consumed by population groups that have not been traditional
      consumers of the grain.

PMID- 27694644
TI  - Transition in ADHD: attention to the lifespan.
AB  - OBJECTIVES: This paper reviews the importance of transition to adult services for
      young people with ADHD. METHOD: Different models are described and evidence
      sought for their effectiveness in clinical practice. RESULTS: Models of care for
      children with ADHD include specialised mental health services, individual
      paediatricians and child and adolescent psychiatrists. Although it might be
      expected that transition would be to equivalent adult teams or specialists,
      studies have shown that transition may not run smoothly, and the adult services
      are frequently inadequate. This may result in attrition from treatment or
      discharge to the general practitioner. CONCLUSIONS: Adult mental health services
      for transitioning young people with ADHD are under-resourced. The way forward may
      be a generic ADHD specialist or service, treating ADHD across the lifespan and
      avoiding the need for transition.

PMID- 27694645
TI  - Alcohol, drug and related health and wellbeing issues among young people
      completing an online screen.
AB  - OBJECTIVE: Despite high levels of alcohol use, drug use and risky behaviors,
      rates of help-seeking amongst young people are typically low. This study explored
      the profile of young people (under the age of 25 years) completing an online
      screen, assessing substance use problem severity and wellbeing in comparison with
      adults completing the same screen, so as to inform development of better targeted
      approaches for this in-need population. METHODS: Between 2012 and 2014, an online
      alcohol and drug screen was promoted across Australia on a national online
      counseling service. The screen assessed severity of substance use, mental health
      and wellbeing. RESULTS: A total of 2939 screens were completed between December
      2012 and May 2014, with 18% completed by young people. Young people reported a
      high severity of substance use problems (44% reported likely drug dependence) and
      reported significantly poorer mental health and wellbeing than adults completing
      the screen. This suggests that there is a population of young people in need of
      support who could be initially engaged through online screening. CONCLUSIONS:
      Online screening should be a key component of engagement strategies for
      adolescent and early adult help-seeking.

PMID- 27694646
TI  - The conundrum of hanging points in correctional facilities.
AB  - OBJECTIVE: We aimed to explore aspects of the removal of hanging points from
      correctional facilities. CONCLUSION: An argument can be made that individuals
      have a right to die/suicide. The United Nations holds that except for freedom of
      movement, prisoners have the same rights as non-prisoners. The rights of the
      individual and the duty of many custodial institutions are in conflict. This
      introduces a conundrum; when all hanging points are removed from correctional
      facilities, prisoners without mental disorder, but with a sustained wish to die,
      will not be able to achieve that end, while non-prisoners will be well able to do
      so.

PMID- 27694647
TI  - Diabetes Dictating Policy: An Editorial Commemorating World Health Day 2016.
AB  - The 21st century is an era of great challenge for humankind; we are combating
      terrorism, climate change, poverty, human rights issues and last but not least
      non-communicable diseases (NCDs). The burden of the latter has become so large
      that it is being recognized by world leaders globally as an area that it is in
      need of much greater attention. In light of this concern, the World Health
      Organization (WHO) dedicated this year's World Health Day (held on April 7, 2016)
      to raising international awareness on diabetes, the fastest growing NCD in the
      world. This editorial is an account of the macro politics in place for fighting
      diabetes, both internationally and nationally.

PMID- 27694648
TI  - Health Departments' Engagement in Emergency Preparedness Activities: The
      Influence of Health Informatics Capacity.
AB  - BACKGROUND: Local health departments (LHDs) operate in a complex and dynamic
      public health landscape, with changing demands on their emergency response
      capacities. Informatics capacities might play an instrumental role in aiding LHDs
      emergency preparedness. This study aimed to explore the extent to which LHDs'
      informatics capacities are associated with their activity level in emergency
      preparedness and to identify which health informatics capacities are associated
      with improved emergency preparedness. METHODS: We used the 2013 National Profile
      of LHDs study to perform Poisson regression of emergency preparedness activities.
      RESULTS: Only 38.3% of LHDs participated in full-scale exercises or drills for an
      emergency in the 12 months period prior to the survey, but a much larger
      proportion provided emergency preparedness training to staff (84.3%), and/or
      participated in tabletop exercises (76.4%). Our multivariable analysis showed
      that after adjusting for several resource-related LHD characteristics, LHDs with
      more of the 6 information systems still tend to have slightly more preparedness
      activities. In addition, having a designated emergency preparedness coordinator,
      and having one or more emergency preparedness staff were among the most
      significant factors associated with LHDs performing more emergency preparedness
      activities. CONCLUSION: LHDs might want to utilize better health information
      systems and information technology tools to improve their activity level in
      emergency preparedness, through improved information dissemination, and evidence
      collection.

PMID- 27694649
TI  - Planning and Budgeting for Nutrition Programs in Tanzania: Lessons Learned From
      the National Vitamin A Supplementation Program.
AB  - BACKGROUND: Micronutrient deficiency in Tanzania is a significant public health
      problem, with vitamin A deficiency (VAD) affecting 34% of children aged 6 to 59
      months. Since 2007, development partners have worked closely to advocate for the
      inclusion of twice-yearly vitamin A supplementation and deworming (VASD)
      activities with budgets at the subnational level, where funding and
      implementation occur. As part of the advocacy work, a VASD planning and budgeting
      tool (PBT) was developed and is used by district officials to justify allocation
      of funds. Helen Keller International (HKI) and the Tanzania Food and Nutrition
      Centre (TFNC) conduct reviews of VASD funds and health budgets annually in all
      districts to monitor the impact of advocacy efforts. This paper presents the
      findings of the fiscal year (FY) 2010 district budget annual review. The review
      was intended to answer the following questions regarding district-level funding:
      (1) how many funds were allocated to nutrition-specific activities in FY 2010?
      (2) how many funds were allocated specifically to twice-yearly VASD activities in
      FY 2010? and (3) how have VASD funding allocations changed over time? METHODS:
      Budgets from all 133 districts in Tanzania were accessed, reviewed and documented
      to identify line item funds allocated for VASD and other nutrition activities in
      FY 2010. Retrospective data from prior annual reviews for VASD were used to track
      trends in funding. The data were collected using specific data forms and then
      transcribed into an excel spreadsheet for analysis. RESULTS: The total funds
      allocated in Tanzania's districts in FY 2010 amounted to US$1.4 million of which
      92% were for VASD. Allocations for VASD increased from US$0.387 million to US$1.3
      million between FY 2005 and FY 2010. Twelve different nutrition activities were
      identified in budgets across the 133 districts. Despite the increased trend, the
      percentage of districts allocating sufficient funds to implement VAS (as defined
      by cost per child) was just 21%. DISCUSSION: District-driven VAS funding in
      Tanzania continues to be allocated by districts consistently, although adequacy
      of funding is a concern. However, regular administrative data point to fairly
      high and consistent coverage rates for VAS across the country (over 80% over the
      last 10 years). Although this analysis may have omitted some nutrition-specific
      funding not identified in district budget data, it represents a reliable
      reflection of the nutrition funding landscape in FY 2010. For this year, total
      district nutrition allocations add up to only 2% of the amount needed to
      implement nutrition services at scale according to Tanzania's National Nutrition
      Strategy Implementation Plan. CONCLUSION: VASD advocacy and planning support at
      the district level has succeeded in ensuring district allocations for the
      program. To promote sustainable implementation of other nutrition interventions
      in Tanzania, more funds must be allocated and guidance must be accompanied by
      tools that enable planning and budgeting at the district level.

PMID- 27694650
TI  - National Health Service Principles as Experienced by Vulnerable London Migrants
      in "Austerity Britain": A Qualitative Study of Rights, Entitlements, and Civil
      Society Advocacy.
AB  - BACKGROUND: Recent British National Health Service (NHS) reforms, in response to
      austerity and alleged 'health tourism,' could impose additional barriers to
      healthcare access for non-European Economic Area (EEA) migrants. This study
      explores policy reform challenges and implications, using excerpts from the
      perspectives of non-EEA migrants and health advocates in London. METHODS: A
      qualitative study design was selected. Data were collected through document
      review and 22 in-depth interviews with non-EEA migrants and civil-society
      organisation representatives. Data were analysed thematically using the NHS
      principles. RESULTS: The experiences of those 'vulnerable migrants' (ie, defined
      as adult non-EEA asylum-seekers, refugees, undocumented, low-skilled, and
      trafficked migrants susceptible to marginalised healthcare access) able to access
      health services were positive, with healthcare professionals generally
      demonstrating caring attitudes. However, general confusion existed about
      entitlements due to recent NHS changes, controversy over 'health tourism,' and
      challenges registering for health services or accessing secondary facilities.
      Factors requiring greater clarity or improvement included accessibility,
      communication, and clarity on general practitioner (GP) responsibilities and
      migrant entitlements. CONCLUSION: Legislation to restrict access to healthcare
      based on immigration status could further compromise the health of vulnerable
      individuals in Britain. This study highlights current challenges in health
      services policy and practice and the role of non-governmental organizations
      (NGOs) in healthcare advocacy (eg, helping the voices of the most vulnerable
      reach policy-makers). Thus, it contributes to broadening national discussions and
      enabling more nuanced interpretation of ongoing global debates on immigration and
      health.

PMID- 27694651
TI  - Politics, Power, Poverty and Global Health: Systems and Frames.
AB  - Striking disparities in access to healthcare and in health outcomes are major
      characteristics of health across the globe. This inequitable state of global
      health and how it could be improved has become a highly popularized field of
      academic study. In a series of articles in this journal the roles of power and
      politics in global health have been addressed in considerable detail. Three
      points are added here to this debate. The first is consideration of how the use
      of definitions and common terms, for example 'poverty eradication,' can mask full
      exposure of the extent of rectification required, with consequent failure to
      understand what poverty eradication should mean, how this could be achieved and
      that a new definition is called for. Secondly, a criticism is offered of how the
      term 'global health' is used in a restricted manner to describe activities that
      focus on an anthropocentric and biomedical conception of health across the world.
      It is proposed that the discourse on 'global health' should be extended beyond
      conventional boundaries towards an ecocentric conception of global/planetary
      health in an increasingly interdependent planet characterised by a multitude of
      interlinked crises. Finally, it is noted that the paucity of workable strategies
      towards achieving greater equity in sustainable global health is not so much due
      to lack of understanding of, or insight into, the invisible dimensions of power,
      but is rather the outcome of seeking solutions from within belief systems and
      cognitive biases that cannot offer solutions. Hence the need for a new framing
      perspective for global health that could reshape our thinking and actions.

PMID- 27694652
TI  - The Evolving Role of Physicians - Don't Forget the Generalist Primary Care
      Providers Comment on "Non-physician Clinicians in Sub-Saharan Africa and the
      Evolving Role of Physicians".
AB  - The editorial "Non-physician Clinicians in Sub-Saharan Africa and the Evolving
      Role of Physicians" by Eyal et al describes non-physician clinicians' (NPC) need
      for mentorship and support from physicians. We emphasise the same need of support
      for front line generalist primary healthcare providers who carry out complex
      tasks yet may have an inadequate skill mix.

PMID- 27694653
TI  - Decentralisation, Decision Space and Directions for Future Research Comment on
      "Decentralisation of Health Services in Fiji: A Decision Space Analysis".
AB  - Decentralisation continues to re-appear in health system reform across the world.
      Evaluation of these reforms reveals how research on decentralisation continues to
      evolve. In this paper, we examine the theoretical foundations and empirical
      references which underpin current approaches to studying decentralisation in
      health systems.

PMID- 27694654
TI  - Implementing Health in All Policies - Time and Ideas Matter Too! Comment on
      "Understanding the Role of Public Administration in Implementing Action on the
      Social Determinants of Health and Health Inequities".
AB  - Carey and Friel suggest that we turn to knowledge developed in the field of
      public administration, especially new public governance, to better understand the
      process of implementing health in all policies (HiAP). In this commentary, I
      claim that theories from the policy studies bring a broader view of the policy
      process, complementary to that of new public governance. Drawing on the policy
      studies, I argue that time and ideas matter to HiAP implementation, alongside
      with interests and institutions. Implementing HiAP is a complex process
      considering that it requires the involvement and coordination of several policy
      sectors, each with their own interests, institutions and ideas about the policy.
      Understanding who are the actors involved from the various policy sectors
      concerned, what context they evolve in, but also how they own and frame the
      policy problem (ideas), and how this has changed over time, is crucial for those
      involved in HiAP implementation so that they can relate to and work together with
      actors from other policy sectors.

PMID- 27694655
TI  - Looking Beyond FDA Warning Letters to Explore Unforeseen Trouble Spots in eDTCA:
      A Response to Recent Commentaries.

PMID- 27694656
TI  - Without Explicit Targets, Does France Meet Minimum Volume Thresholds for Hip and
      Knee Replacement and Bariatric Surgeries?

PMID- 27694657
TI  - Legalizing and Regulating Marijuana in Canada: Review of Potential Economic,
      Social, and Health Impacts.
AB  - Notwithstanding a century of prohibition, marijuana is the most widely used
      illicit substance in Canada. Due to the growing public acceptance of recreational
      marijuana use and ineffectiveness of the existing control system in Canada, the
      issue surrounding legalizing this illicit drug has received considerable public
      and political attentions in recent years. Consequently, the newly elected Liberal
      Government has formally announced that Canada will introduce legislation in the
      spring of 2017 to start legalizing and regulating marijuana. This editorial aims
      to provide a brief overview on potential economic, social, and public health
      impacts of legal marijuana in Canada. The legalization could increase tax revenue
      through the taxation levied on marijuana products and could also allow the
      Government to save citizens' tax dollars currently being spent on prohibition
      enforcement. Moreover, legalization could also remove the criminal element from
      marijuana market and reduce the size of Canada's black market and its
      consequences for the society. Nevertheless, it may also lead to some public
      health problems, including increasing in the uptake of the drug, accidents and
      injuries. The legalization should be accompanied with comprehensive strategies to
      keep the drug out of the hands of minors while increasing awareness and knowledge
      on harmful effects of the drug. In order to get better insights on how to develop
      an appropriate framework to legalize marijuana, Canada should closely watch the
      development in the neighboring country, the United States, where some of its
      states viz, Colorado, Oregon, Washington, and Alaska have already legalized
      recreational use of marijuana.

PMID- 27694658
TI  - Defining and Acting on Global Health: The Case of Japan and the Refugee Crisis.
AB  - What counts as global health? There has been limited discourse to date on the
      ways in which country-level contexts may shape positioning in global health
      agendas. By reviewing Japan's response to the refugee crisis, we demonstrate a
      clash between rhetoric and action on global responsibility, and suggest that
      cultural and historical factors may be related to the ways of perceiving and
      acting upon global health.

PMID- 27694659
TI  - Assessing Patient Participation in Health Policy Decision-Making in Cyprus.
AB  - Although the importance of patient participation in the design and evaluation of
      health programs and services is well-documented, there is scarcity of research
      with regard to patient association (PA) participation in health policy decision
      making processes. To this end, the present study aimed to validate further a
      previously developed instrument as well as to investigate the degree of PA
      participation in health policy decision-making in Cyprus. A convenient sample of
      114 patients-members of patients associations took part in the study.
      Participants were recruited from an umbrella organization, the Pancyprian
      Federation of Patient Associations and Friends (PFPA). PA participation in health
      policy decision-making was assessed with the Health Democracy Index (HDI), an
      original 8-item tool. To explore its psychometric properties, Cronbach alpha was
      computed as regards to its internal consistency, while its convergent validity
      was tested against a self-rated question enquiring about the degree of PA
      participation in health policy decision-making. The findings revealed that the
      HDI has good internal consistency and convergent validity. Furthermore, PAs were
      found to participate more in consultations in health-related organizations and
      the Ministry of Health (MoH) as well as in reforms or crucial decisions in health
      policy. Lower levels were documented with regard to participation in hospital
      boards, ethics committees in clinical trials and health technology assessment
      (HTA) procedures. Overall, PA participation levels were found to be lower than
      the mid-point of the scale. Targeted interventions aiming to facilitate patients'
      involvement in health policy decision-making processes and to increase its impact
      are greatly needed in Cyprus.

PMID- 27694660
TI  - Motivation and Retention of Physicians in Primary Healthcare Facilities: A
      Qualitative Study From Abbottabad, Pakistan.
AB  - BACKGROUND: Workforce motivation and retention is important for the functionality
      and quality of service delivery in health systems of developing countries.
      Despite huge primary healthcare (PHC) infrastructure, Pakistan's health
      indicators are not impressive; mainly because of under-utilization of facilities
      and low patient satisfaction. One of the major underlying issues is staff
      absenteeism. The study aimed to identify factors affecting retention and
      motivation of doctors working in PHC facilities of Pakistan. METHODS: An
      exploratory study was conducted in a rural district in Khyber Puktunkhwa (KP)
      province, in Pakistan. A conceptual framework was developed comprising of three
      organizational, individual, and external environmental factors. Qualitative
      research methods comprising of semi-structured interviews with doctors working in
      basic health units (BHUs) and in-depth interviews with district and provincial
      government health managers were used. Document review of postings, rules of
      business and policy actions was also conducted. Triangulation of findings was
      carried out to arrive at the final synthesis. RESULTS: Inadequate remuneration,
      unreasonable facilities at residence, poor work environment, political
      interference, inadequate supplies and medical facilities contributed to lack of
      motivation among both male and female doctors. The physicians accepted government
      jobs in BHUs with a belief that these jobs were more secure, with convenient
      working hours. Male physicians seemed to be more motivated because they faced
      less challenges than their female counterparts in BHUs especially during
      relocations. Overall, the organizational factors emerged as the most significant
      whereby human resource policy, career growth structure, performance appraisal and
      monetary benefits played an important role. Gender and marital status of female
      doctors was regarded as most important individual factor affecting retention and
      motivation of female doctors in BHUs. CONCLUSION: Inadequate remuneration,
      unreasonable facilities at residence, poor work environment, political
      interference, inadequate supplies, and medical facilities contributed to lack of
      motivation in physicians in our study. Our study advocates that by addressing the
      retention and motivation challenges, service delivery can be made more responsive
      to the patients and communities in Pakistan and other similar settings.

PMID- 27694662
TI  - The Trans-Pacific Partnership: Is It Everything We Feared for Health?
AB  - BACKGROUND: Negotiations surrounding the Trans-Pacific Partnership (TPP) trade
      and investment agreement have recently concluded. Although trade and investment
      agreements, part of a broader shift to global economic integration, have been
      argued to be vital to improved economic growth, health, and general welfare,
      these agreements have increasingly come under scrutiny for their direct and
      indirect health impacts. METHODS: We conducted a prospective health impact
      analysis to identify and assess a selected array of potential health risks of the
      TPP. We adapted the standard protocol for Health impact assessments (HIAs)
      (screening, scoping, and appraisal) to our aim of assessing potential health
      risks of trade and investment policy, and selected a health impact review
      methodology. This methodology is used to create a summary estimation of the most
      significant impacts on health of a broad policy or cluster of policies, such as a
      comprehensive trade and investment agreement. RESULTS: Our analysis shows that
      there are a number of potentially serious health risks associated with the TPP,
      and details a range of policy implications for the health sector. Of particular
      focus are the potential implications of changes to intellectual property rights
      (IPRs), sanitary and phytosanitary measures (SPS), technical barriers to trade
      (TBT), investor-state dispute settlement (ISDS), and regulatory coherence
      provisions on a range of issues, including access to medicines and health
      services, tobacco and alcohol control, diet-related health, and domestic health
      policy-making. CONCLUSION: We provide a list of policy recommendations to
      mitigate potential health risks associated with the TPP, and suggest that broad
      public consultations, including on the health risks of trade and investment
      agreements, should be part of all trade negotiations.

PMID- 27694661
TI  - Developing Leadership in Managers to Facilitate the Implementation of National
      Guideline Recommendations: A Process Evaluation of Feasibility and Usefulness.
AB  - BACKGROUND: Previous research supports the claim that managers are vital players
      in the implementation of clinical practice guidelines (CPGs), yet little is known
      about interventions aiming to develop managers' leadership in facilitating
      implementation. In this pilot study, process evaluation was employed to study the
      feasibility and usefulness of a leadership intervention by exploring the
      intervention's potential to support managers in the implementation of national
      guideline recommendations for stroke care in outpatient rehabilitation. METHODS:
      Eleven senior and frontline managers from five outpatient stroke rehabilitation
      centers participated in a four-month leadership intervention that included
      workshops, seminars, and teleconferences. The focus was on developing knowledge
      and skills to enhance the implementation of CPG recommendations, with a
      particular focus on leadership behaviors. Each dyad of managers was assigned to
      develop a leadership plan with specific goals and leadership behaviors for
      implementing three rehabilitation recommendations. Feasibility and usefulness
      were explored through observations and interviews with the managers and staff
      members prior to the intervention, and then one month and one year after the
      intervention. RESULTS: Managers considered the intervention beneficial,
      particularly the participation of both senior and frontline managers and the
      focus on leadership knowledge and skills for implementing CPG recommendations.
      All the managers developed a leadership plan, but only two units identified goals
      specific to implementing the three stroke rehabilitation recommendations. Of
      these, only one identified leadership behaviors that support implementation.
      CONCLUSION: Managers found that the intervention was delivered in a feasible way
      and appreciated the focus on leadership to facilitate implementation. However,
      the intervention appeared to have limited impact on managers' behaviors or
      clinical practice at the units. Future interventions directed towards managers
      should have a stronger focus on developing leadership skills and behaviors to
      tailor implementation plans and support implementation of CPG recommendations.

PMID- 27694663
TI  - Priority Setting Meets Multiple Streams: A Match to Be Further Examined? Comment
      on "Introducing New Priority Setting and Resource Allocation Processes in a
      Canadian Healthcare Organization: A Case Study Analysis Informed by Multiple
      Streams Theory.
AB  - With demand for health services continuing to grow as populations age and new
      technologies emerge to meet health needs, healthcare policy-makers are under
      constant pressure to set priorities, ie, to make choices about the health
      services that can and cannot be funded within available resources. In a recent
      paper, Smith et al apply an influential policy studies framework - Kingdon's
      multiple streams approach (MSA) - to explore the factors that explain why one
      health service delivery organization adopted a formal priority setting framework
      (in the form of programme budgeting and marginal analysis [PBMA]) to assist it in
      making priority setting decisions. MSA is a theory of agenda-setting, ie, how it
      is that different issues do or do not reach a decision-making point. In this
      paper, I reflect on the use of the MSA framework to explore priority setting
      processes and how the framework might be applied to similar cases in future.

PMID- 27694664
TI  - HTA - Algorithm or Process? Comment on "Expanded HTA: Enhancing Fairness and
      Legitimacy".
AB  - Daniels, Porteny and Urrutia et al make a good case for the idea that that public
      decisions ought to be made not only "in the light of" evidence but also "on the
      basis of" budget impact, financial protection and equity. Health technology
      assessment (HTA) should, they say, be accordingly expanded to consider matters
      additional to safety and cost-effectiveness. They also complain that most HTA
      reports fail to develop ethical arguments and generally do not even mention
      ethical issues. This comment argues that some of these defects are more apparent
      than real and are not inherent in HTA - as distinct from being common
      characteristics found in poorly conducted HTAs. More generally, HTA does not need
      "extension" since (1) ethical issues are already embedded in HTA processes, not
      least in their scoping phases, and (2) HTA processes are already sufficiently
      flexible to accommodate evidence about a wide range of factors, and will not need
      fundamental change in order to accommodate the new forms of decision-relevant
      evidence about distributional impact and financial protection that are now
      starting to emerge. HTA and related techniques are there to support decision
      makers who have authority to make decisions. Analysts like us are there to
      support and advise them (and not to assume the responsibilities for which they,
      and not we, are accountable). The required quality in HTA then becomes its
      effectiveness as a means of addressing the issues of concern to decision-makers.
      What is also required is adherence by competent analysts to a standard template
      of good analytical practice. The competencies include not merely those of the
      usual disciplines (particularly biostatistics, cognitive psychology, health
      economics, epidemiology, and ethics) but also the imaginative and interpersonal
      skills for exploring the "real" question behind the decision-maker's brief
      (actual or postulated) and eliciting the social values that necessarily pervade
      the entire analysis. The product of such exploration defines the authoritative
      scope of an HTA.

PMID- 27694665
TI  - Governance in Health - The Need for Exchange and Evidence Comment on "Governance,
      Government, and the Search for New Provider Models".
AB  - Governance in health is cited as one of the key factors in balancing the concerns
      of the government and public sector with the interests of civil society/private
      players, but often remains poorly described and operationalized. Richard Saltman
      and Antonio Duran look at two aspects in the search for new provider models in a
      context of health markets signalling liberalisation: (i) the role of the
      government to balance public and private interests and responsibilities in
      delivering care through modernised governance arrangements, and (ii) the finding
      that operational complexities may hinder well-designed provider governance
      models, unless governance reflects country-specific realities. This commentary
      builds on the discussion by Saltman and Duran, and argues that the concept of
      governance needs to be clearly defined and operationalized in order to be helpful
      for policy debate as well as for the development of an applicable framework for
      performance improvement. It provides a working definition of governance and
      includes a reflection on the prevailing cultural norms in an organization or
      society upon which any governance needs to be build. It proposes to explore
      whether the "evidence-based governance" concept can be introduced to generate
      knowledge about innovative and effective governance models, and concludes that
      studies similar to the one by Saltman and Duran can inform this debate.

PMID- 27694666
TI  - Risks and Opportunities of Reforms Putting Primary Care in the Driver's Seat
      Comment on "Governance, Government, and the Search for New Provider Models".
AB  - Recognizing the advantages of primary care as a means of improving the entire
      health system, this text comments on reforms of publicly funded primary health
      centers, and the rapid development of private for-profit providers in Sweden.
      Many goals and expectations are connected to such reforms, which equally require
      critical analyses of scarce resources, professional trust/motivation and business
      logic in the wake of freedom and control of ownership and management. In line
      with Saltman and Duran, this article calls for research and a methodologically
      developed approach to capture everyday practice in-depth and how regulation,
      market incentives and patient demands are met by professionals and primary care
      leaders.

PMID- 27694667
TI  - Needed: Global Collaboration for Comparative Research on Cities and Health.
AB  - Over half of the world's population lives in cities and United Nations (UN)
      demographers project an increase of 2.5 billion more urban dwellers by 2050. Yet
      there is too little systematic comparative research on the practice of urban
      health policy and management (HPAM), particularly in the megacities of middle
      income and developing nations. We make a case for creating a global database on
      cities, population health and healthcare systems. The expenses involved in data
      collection would be difficult to justify without some review of previous work,
      some agreement on indicators worth measuring, conceptual and methodological
      considerations to guide the construction of the global database, and a set of
      research questions and hypotheses to test. We, therefore, address these issues in
      a manner that we hope will stimulate further discussion and collaboration.

PMID- 27694668
TI  - What Can We Learn About the Processes of Regulation of Tuberculosis Medicines
      From the Experiences of Health Policy and System Actors in India, Tanzania, and
      Zambia?
AB  - BACKGROUND: The unregulated availability and irrational use of tuberculosis (TB)
      medicines is a major issue of public health concern globally. Governments of many
      low- and middle-income countries (LMICs) have committed to regulating the quality
      and availability of TB medicines, but with variable success. Regulation of TB
      medicines remains an intractable challenge in many settings, but the reasons for
      this are poorly understood. The objective of this paper is to elaborate processes
      of regulation of quality and availability of TB medicines in three LMICs - India,
      Tanzania, and Zambia - and to understand the factors that constrain and enable
      these processes. METHODS: We adopted the action-centred approach of policy
      implementation analysis that draws on the experiences of relevant policy and
      health system actors in order to understand regulatory processes. We drew on data
      from three case studies commissioned by the World Health Organization (WHO), on
      the regulation of TB medicines in India, Tanzania, and Zambia. Qualitative
      research methods were used, including in-depth interviews with 89 policy and
      health system actors and document review. Data were organized thematically into
      accounts of regulators' authority and capacity; extent of policy implementation;
      and efficiency, transparency, and accountability. RESULTS: In India, findings
      included the absence of a comprehensive policy framework for regulation of TB
      medicines, constraints of authority and capacity of regulators, and poor
      implementation of prescribing and dispensing norms in the majority private
      sector. Tanzania had a policy that restricted import, prescribing and dispensing
      of TB medicines to government operators. Zambia procured and dispensed TB
      medicines mainly through government services, albeit in the absence of a single
      policy for restriction of medicines. Three cross-cutting factors emerged as
      crucially influencing regulatory processes - political and stakeholder support
      for regulation, technical and human resource capacity of regulatory bodies, and
      the manner of private actors' influence on regulatory policy and implementation.
      CONCLUSION: Strengthening regulation to ensure the quality and availability of TB
      medicines in LMIC with emerging private markets may necessitate financial and
      technical inputs to upgrade regulatory bodies, as well as broader political and
      ethical actions to reorient and transform their current roles.

PMID- 27694669
TI  - Catastrophic Health Expenditure After the Implementation of Health Sector
      Evolution Plan: A Case Study in the West of Iran.
AB  - BACKGROUND: One of the main objectives of health systems is the financial
      protection against out-of-pocket (OOP) health expenditures. OOP health
      expenditures can lead to catastrophic payments, impoverishment or poverty among
      households. In Iran, health sector evolution plan (HSEP) has been implemented
      since 2014 in order to achieve universal health coverage and reduce the OOP
      health expenditures as a percentage of total health expenditures. This study
      aimed to explore the percentage of households facing catastrophic health
      expenditures (CHE) after the implementation of HSEP and the factors that
      determine CHE. METHODS: A total of 663 households were selected through a cluster
      sampling based on the census framework of Sanandaj Health Center in July 2015.
      Data were gathered using face-to-face interviews based on the household section
      of the World Health Survey questionnaire. In this study, according to the World
      Health Organization (WHO) definition, if household health expenditures were equal
      to or more than 40% of the household capacity to pay, household was considered to
      be facing CHE. The determinants of CHE were analyzed using logistic regression
      model. RESULTS: The rates of households facing CHE were 4.8%. The key
      determinants of CHE were household economic status, presence of elderly or
      disabled members in the household and utilization of inpatient or rehabilitation
      services. CONCLUSION: The comparison of our findings and those of other studies
      carried out using a methodology comparable with ours in different parts of Iran
      before the implementation of HSEP suggests that the implementation of recent
      reforms has reduced CHE at the household level. Utilization of inpatient and
      rehabilitation services, the presence of elderly or disabled members in the
      household and the low economic status of the household would increase the
      likelihood of facing CHE. These variables should be considered by health policy
      makers in order to review and revise content of recent reform, thus financially
      protecting public against CHE.

PMID- 27694671
TI  - The Health Policy Process in Vietnam: Going Beyond Kingdon's Multiple Streams
      TheoryComment on "Shaping the Health Policy Agenda: The Case of Safe Motherhood
      Policy in Vietnam".
AB  - This commentary reflects upon the article along three broad lines. It reflects on
      the theoretical choices and omissions, particularly highlighting why it is
      important to adapt the multiple streams framework (MSF) when applying it in a
      socio-political context like Vietnam's. The commentary also reflects upon the
      analytical threads tackled by Ha et al; for instance, it highlights the
      opportunities offered by, and raises questions about the centrality of the Policy
      Entrepreneur in getting the policy onto the political agenda and in pushing it
      through. The commentary also dwells on the implications of the article for
      development aid policies and practices. Throughout, the commentary signposts
      possible themes for Ha et al to consider for further analysis, and more
      generally, for future research using Kingdon's multiple streams theory.

PMID- 27694670
TI  - Adoption of Electronic Personal Health Records in Canada: Perceptions of
      Stakeholders.
AB  - BACKGROUND: Healthcare stakeholders have a great interest in the adoption and use
      of electronic personal health records (ePHRs) because of the potential benefits
      associated with them. Little is known, however, about the level of adoption of
      ePHRs in Canada and there is limited evidence concerning their benefits and
      implications for the healthcare system. This study aimed to describe the current
      situation of ePHRs in Canada and explore stakeholder perceptions regarding
      barriers and facilitators to their adoption. METHODS: Using a qualitative
      descriptive study design, we conducted semi-structured phone interviews between
      October 2013 and February 2014 with 35 individuals from seven Canadian provinces.
      The participants represented six stakeholder groups (patients, ePHR
      administrators, healthcare professionals, organizations interested in health
      technology development, government agencies, and researchers). A detailed summary
      of each interview was created and thematic analysis was conducted. RESULTS: We
      observed that there was no consensual definition of ePHR in Canada. Factors that
      could influence ePHR adoption were related to knowledge (confusion with other
      electronic medical records [EMRs] and lack of awareness), system design
      (usability and relevance), user capacities and attitudes (patient health
      literacy, education and interest, support for professionals), environmental
      factors (government commitment, targeted populations) and legal and ethical
      issues (information control and custody, confidentiality, privacy and security).
      CONCLUSION: ePHRs are slowly entering the Canadian healthcare landscape but
      provinces do not seem well-prepared for the implementation of this type of
      record. Guidance is needed on critical issues regarding ePHRs, such as ePHR
      definition, data ownership, access to information and interoperability with other
      electronic health records (EHRs). Better guidance on these issues would provide a
      greater awareness of ePHRs and inform stakeholders including clinicians, decision
      makers, patients and the public. In turn, it may facilitate their adoption in the
      country.

PMID- 27694672
TI  - From Headline to Hard Grind: The Importance of Understanding Public
      Administration in Achieving Health OutcomesComment on "Understanding the Role of
      Public Administration in Implementing Action on the Social Determinants of Health
      and Health Inequities".
AB  - Many public policy programs fail to translate ambitious headlines to on-the
      ground action. The reasons for this are many and varied, but for public
      administration and management scholars a large part of the gap between ambition
      and achievement is the challenge associated with the operation of the machinery
      of government itself, and how it relates to the other parties that it relies on
      to fulfill these outcomes. In their article, Carey and Friel set out key reasons
      why public health scholars should seek to better understand important ideas in
      public administration. In commenting on their contribution, I draw out two
      critical questions that are raised by this discussion: (i) what are boundaries
      and what forms do they take? and (ii) why work across boundaries? Expanding on
      these key questions extends the points made by Carey and Friel on the importance
      of understanding public administration and will better place public health
      scholars and practitioners to realise health outcomes.

PMID- 27694673
TI  - Decision Space and Capacities in the Decentralization of Health Services in
      FijiComment on "Decentralisation of Health Services in Fiji: A Decision Space
      Analysis".
AB  - The study of decentralization in Fiji shows that increasing capacities is not
      necessarily related to increasing decision space of local officials, which is in
      contrast with earlier studies in Pakistan. Future studies should address the
      relationship among decision space, capacities, and health system performance.

PMID- 27694674
TI  - Defining Pathways and Trade-offs Toward Universal Health CoverageComment on
      "Ethical Perspective: Five Unacceptable Trade-offs on the Path to Universal
      Health Coverage".
AB  - The World Health Organization's (WHO's) World Health Report 2010, "Health systems
      financing, the path to universal coverage," promoted universal health coverage
      (UHC) as an aspirational objective for country health systems. Yet, in addition
      to the dimensions of services and coverage, distribution of coverage in the
      population, and financial risk protection highlighted by the report, the
      consideration of the budget constraint should be further strengthened in the
      ensuing debate on resource allocation toward UHC. Beyond the substantial
      financial constraints faced by low- and middle-income countries, additional
      considerations, such as the geographical context, the underlying country
      infrastructure, and the architecture of health systems, determine the
      feasibility, effectiveness, quality and cost of healthcare delivery. Therefore,
      increased production and use of local evidence tied to the criteria of health
      benefits, equity, financial risk protection, and costs accompanying health
      delivery are needed so that to highlight pathways and acceptable trade-offs
      toward UHC.

PMID- 27694675
TI  - Of Politicians and Technocrats, and Why Global Health Scholars Are Inevitably a
      Bit of Both: A Response to Recent Commentaries.

PMID- 27694676
TI  - Do Financial Incentives Increase Doctors' Willingness to Publish Research? - A
      Pilot Study of 21 Junior Doctors.

PMID- 27694677
TI  - Strategic Faults in Implementation of Hospital Accreditation Programs in
      Developing Countries: Reflections on the Iranian Experience.
AB  - Establishment of hospital accreditation programs is increasingly growing across
      numerous developing nations. Such initiatives aim to improve quality of care.
      However, such establishments, mainly incentivized by successful and famous
      accreditation plans in developed countries, usually suffer from lack of necessary
      arrangements which, in turn, result in undesired consequences. Indeed, the first
      priority for such nations, including Iran, is not establishment of accreditation
      programs, yet strict licensing plans.

PMID- 27694678
TI  - UK and Twenty Comparable Countries GDP-Expenditure-on-Health 1980-2013: The
      Historic and Continued Low Priority of UK Health-Related Expenditure.
AB  - It is well-established that for a considerable period the United Kingdom has
      spent proportionally less of its gross domestic product (GDP) on health-related
      services than almost any other comparable country. Average European spending on
      health (as a % of GDP) in the period 1980 to 2013 has been 19% higher than the
      United Kingdom, indicating that comparable countries give far greater fiscal
      priority to its health services, irrespective of its actual fiscal value or
      configuration. While the UK National Health Service (NHS) is a comparatively lean
      healthcare system, it is often regarded to be at a 'crisis' point on account of
      low levels of funding. Indeed, many state that currently the NHS has a sizeable
      funding gap, in part due to its recently reduced GDP devoted to health but mainly
      the challenges around increases in longevity, expectation and new medical costs.
      The right level of health funding is a political value judgement. As the data in
      this paper outline, if the UK 'afforded' the same proportional level of funding
      as the mean average European country, total expenditure would currently increase
      by one-fifth.

PMID- 27694679
TI  - Operationalization of the Ghanaian Patients' Charter in a Peri-urban Public
      Hospital: Voices of Healthcare Workers and Patients.
AB  - BACKGROUND: Health is a basic human right necessary for the exercise of other
      human rights. Every human being is, therefore, entitled to the highest possible
      standard of health necessary to living a life of dignity. Establishment of
      patients' Charter is a step towards protecting the rights and responsibilities of
      patients, but violation of patients' rights is common in healthcare institutions,
      especially in the developing world. This study which was conducted between May
      2013 and May 2014, assessed the operationalization of Ghana's Patients Charter in
      a peri-urban public hospital. METHODS: Qualitative data collection methods were
      used to collect data from 25 healthcare workers and patients who were purposively
      selected. The interview data were analyzed manually, using the principles of
      systematic text condensation. RESULTS: The findings indicate that the healthcare
      staff of the Polyclinic are aware of the existence of the patients' Charter and
      also know some of its contents. Patients have no knowledge of the existence or
      the contents of the Charter. Availability of the Charter, community
      sensitization, monitoring and orientation of staff are factors that promote the
      operationalization of the Charter, while institutional implementation procedures
      such as lack of complaint procedures and low knowledge among patients militate
      against operationalization of the Charter. CONCLUSION: Public health facilities
      should ensure that their patients are well-informed about their rights and
      responsibilities to facilitate effective implementation of the Charter. Also,
      patients' rights and responsibilities can be dramatized and broadcasted on
      television and radio in major Ghanaian languages to enhance awareness of
      Ghanaians on the Charter.

PMID- 27694680
TI  - Correcting India's Chronic Shortage of Drug Inspectors to Ensure the Production
      and Distribution of Safe, High-Quality Medicines.
AB  - BACKGROUND: Good drug regulation requires an effective system for monitoring and
      inspection of manufacturing and sales units. In India, despite widespread
      agreement on this principle, ongoing shortages of drug inspectors have been
      identified by national committees since 1975. The growth of India's
      pharmaceutical industry and its large export market makes the problem more acute.
      METHODS: The focus of this study is a case study of Maharashtra, which has 29% of
      India's manufacturing units and 38% of its medicines exports. India's regulations
      were reviewed, comparing international, national and state inspection norms with
      the actual number of inspectors and inspections. Twenty-six key informant
      interviews were conducted to ascertain the causes of the shortfall. RESULTS: In
      2009-2010, 55% of the sanctioned posts of drug inspectors in Maharashtra were
      vacant. This resulted in a shortfall of 83%, based on the Mashelkar Committee's
      recommendations. Less than a quarter of the required inspections of manufacturing
      and sales units were undertaken. The Indian Drugs and Cosmetics Act and its Rules
      and Regulations make no provisions for drug inspectors and workforce planning
      norms, despite the growth and increasing complexity of India's pharmaceutical
      industry. CONCLUSION: The Maharashtra Food and Drug Administration (FDA) falls
      short of the Mashelkar Committee's recommended workforce planning norms.
      Legislation and political and operational support are required to produce needed
      changes.

PMID- 27694681
TI  - The Politico-Economic Challenges of Ghana's National Health Insurance Scheme
      Implementation.
AB  - BACKGROUND: National/social health insurance schemes have increasingly been seen
      in many low- and middle-income countries (LMICs) as a vehicle to universal health
      coverage (UHC) and a viable alternative funding mechanism for the health sector.
      Several countries, including Ghana, have thus introduced and implemented
      mandatory national health insurance schemes (NHIS) as part of reform efforts
      towards increasing access to health services. Ghana passed mandatory national
      health insurance (NHI) legislation (ACT 650) in 2003 and commenced nationwide
      implementation in 2004. Several peer review studies and other research reports
      have since assessed the performance of the scheme with positive rating while
      challenges also noted. This paper contributes to the literature on economic and
      political implementation challenges based on empirical evidence from the
      perspectives of the different category of actors and institutions involved in the
      process. METHODS: Qualitative in-depth interviews were held with 33 different
      category of participants in four selected district mutual health insurance
      schemes in Southern (two) and Northern (two) Ghana. This was to ascertain their
      views regarding the main challenges in the implementation process. The
      participants were selected through purposeful sampling, stakeholder mapping, and
      snowballing. Data was analysed using thematic grouping procedure. RESULTS:
      Participants identified political issues of over politicisation and political
      interference as main challenges. The main economic issues participants identified
      included low premiums or contributions; broad exemptions, poor gatekeeper
      enforcement system; and culture of curative and hospital-centric care.
      CONCLUSION: The study establishes that political and economic factors have
      influenced the implementation process and the degree to which the policy has been
      implemented as intended. Thus, we conclude that there is a synergy between
      implementation and politics; and achieving UHC under the NHIS requires political
      stewardship. Political leadership has the responsibility to build trust and
      confidence in the system by providing the necessary resources and backing with
      minimal interference in the operations. For sustainability of the scheme,
      authorities need to review the exemption policy, rate of contributions,
      especially, from informal sector employees and recruitment criteria of scheme
      workers, explore additional sources of funding and re-examine training needs of
      employees to strengthen their competences among others.

PMID- 27694682
TI  - Governance: Blending Bureaucratic Rules with Day to Day Operational Realities
      Comment on "Governance, Government, and the Search for New Provider Models".
AB  - Richard Saltman and Antonio Duran take up the challenging issue of governance in
      their article "Governance, Government and the Search for New Provider Models,"
      and use two case studies of health policy changes in Sweden and Spain to shed
      light on the subject. In this commentary, I seek to link their conceptualization
      of governance, especially its interrelated roles at the macro, meso, and micro
      levels of health systems, with the case studies on which they report. While the
      case studies focus on the shifts in governance between the macro and meso levels
      and their impacts on achievement of desired policy outcomes, they also highlight
      the need to better integrate the dynamics of day to day operations within micro
      organizations into the overall governance picture.

PMID- 27694683
TI  - Universal Health Coverage - The Critical Importance of Global Solidarity and Good
      Governance Comment on "Ethical Perspective: Five Unacceptable Trade-offs on the
      Path to Universal Health Coverage".
AB  - This article provides a commentary to Ole Norheim' s editorial entitled "Ethical
      perspective: Five unacceptable trade-offs on the path to universal health
      coverage." It reinforces its message that an inclusive, participatory process is
      essential for ethical decision-making and underlines the crucial importance of
      good governance in setting fair priorities in healthcare. Solidarity on both
      national and international levels is needed to make progress towards the goal of
      universal health coverage (UHC).

PMID- 27694684
TI  - U-Form vs. M-Form: How to Understand Decision Autonomy Under Healthcare
      Decentralization? Comment on "Decentralisation of Health Services in Fiji: A
      Decision Space Analysis".
AB  - For more than three decades healthcare decentralization has been promoted in
      developing countries as a way of improving the financing and delivery of public
      healthcare. Decision autonomy under healthcare decentralization would determine
      the role and scope of responsibility of local authorities. Jalal Mohammed, Nicola
      North, and Toni Ashton analyze decision autonomy within decentralized services in
      Fiji. They conclude that the narrow decision space allowed to local entities
      might have limited the benefits of decentralization on users and providers. To
      discuss the costs and benefits of healthcare decentralization this paper uses the
      U-form and M-form typology to further illustrate the role of decision autonomy
      under healthcare decentralization. This paper argues that when evaluating
      healthcare decentralization, it is important to determine whether the benefits
      from decentralization are greater than its costs. The U-form and M-form framework
      is proposed as a useful typology to evaluate different types of institutional
      arrangements under healthcare decentralization. Under this model, the more
      decentralized organizational form (M-form) is superior if the benefits from
      flexibility exceed the costs of duplication and the more centralized
      organizational form (U-form) is superior if the savings from economies of scale
      outweigh the costly decision-making process from the center to the regions.
      Budgetary and financial autonomy and effective mechanisms to maintain local
      governments accountable for their spending behavior are key decision autonomy
      variables that could sway the cost-benefit analysis of healthcare
      decentralization.

PMID- 27694685
TI  - Expanded HTA, Legitimacy and Independence Comment on "Expanded HTA: Enhancing
      Fairness and Legitimacy".
AB  - This brief commentary seeks to develop the analysis of Daniels, Porteny and
      Urrutia of the implications of expansion of the scope of health technology
      assessment (HTA) beyond issues of safety, efficacy, and cost-effectiveness.
      Drawing in particular on experience in the United Kingdom, it suggests that such
      expansion can be understood not only as a response to the problem of
      insufficiency of evidence, but also to that of legitimacy. However, as expansion
      of HTA also renders it more visibly political in character, it is plausible that
      its legitimacy may be undermined, rather than enhanced by, independence from the
      policy process.

PMID- 27694686
TI  - Re-Conceptualising Public Health Interventions in Government: A Response to
      Recent Commentaries.

PMID- 27694687
TI  - How to implement medical evidence into practice in developing countries.

PMID- 27694688
TI  - MicroRNA-34a regulates doxorubicin-induced cardiotoxicity in rat.
AB  - New strategies to prevent and early detect the cardiotoxic effects of the
      anticancer drug doxorubicin (DOXO) are required. MicroRNAs emerged as potential
      diagnostic, therapeutic and prognostic approaches in cardiovascular diseases. MiR
      34a has a role in cardiac dysfunction and ageing and is involved in several
      cellular processes associated with DOXO cardiotoxicity. Our in vitro and in vivo
      results indicated that after DOXO exposure the levels of miR-34a are enhanced in
      cardiac cells, including Cardiac Progenitor Cells (CPCs). Since one of the
      determining event responsible for the initiation and evolution of the DOXO
      toxicity arises at the level of the CPC compartment, we evaluated if miR-34a
      pharmacological inhibition in these cells ameliorates the detrimental aftermath
      of the drug. AntimiR-34a has beneficial consequences on vitality, proliferation,
      apoptosis and senescence of DOXO-treated rat CPC. These effects are mediated by
      an increase of prosurvival miR-34a targets Bcl-2 and SIRT1, accompanied by a
      decrease of acetylated-p53 and p16INK4a. Importantly, miR-34a silencing also
      reduces the release of this miRNA from DOXO-exposed rCPCs, decreasing its
      negative paracrine effects on other rat cardiac cells. In conclusion, the
      silencing of miR-34a could represent a future therapeutic option for
      cardioprotection in DOXO toxicity and at the same time, it could be considered as
      a circulating biomarker for anthracycline-induced cardiac damage.

PMID- 27694689
TI  - eIF5B increases ASAP1 expression to promote HCC proliferation and invasion.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related
      death worldwide. Despite the therapeutic advances that have been achieved during
      the past decade, the molecular pathogenesis underlying HCC remains poorly
      understood. In this study, we discovered that increased expression eukaryotic
      translation initiation factor 5B (eIF5B) was significantly correlated with
      aggressive characteristics and associated with shorter recurrence-free survival
      (RFS) and overall survival (OS) in a large cohort. We also found that eIF5B
      promoted HCC cell proliferation and migration in vitro and in vivo partly through
      increasing ASAP1 expression. Our findings strongly suggested that eIF5B could
      promote HCC progression and be considered a prognostic biomarker for HCC.

PMID- 27694690
TI  - Suppression of PC-1/PrLZ sensitizes prostate cancer cells to ionizing radiation
      by attenuating DNA damage repair and inducing autophagic cell death.
AB  - Radiotherapy is promising and effective for treating prostate cancer but the
      addition of a tumor cell radiosensitizer would improve therapeutic outcomes. PC
      1/PrLZ, a TPD52 protein family member is frequently upregulated in advanced
      prostate cancer cells and may be a biomarker of aggressive prostate cancer.
      Therefore, we investigated the potential role of PC-1/PrLZ for increasing
      radioresistance in human prostate cancer cell lines. Growth curves and survival
      assays after g-ray irradiation confirmed that depletion of endogenous PC-1/PrLZ
      significantly increased prostate cancer cell radiosensitivity. Irradiation (IR)
      increased PC-1/PrLZ expression in a dose- and time-dependent manner and increased
      radiosensitivity in PC-1/PrLZ-suppressed cells was partially due to decreased DNA
      double strand break (DBS) repair which was measured with comet and gH2AX foci
      assays. Furthermore, depletion of PC-1/PrLZ impaired the IR-induced G2/M
      checkpoint, which has been reported to be correlate with radioresistance in
      cancer cells. PC-1/PrLZ-deficient cells exhibited higher level of autophagy when
      compared with control cells. Thus, specific inhibition of PC-1/PrLZ might provide
      a novel therapeutic strategy for radiosensitizing prostate cancer cells.

PMID- 27694691
TI  - Interleukin-6 expression contributes to lapatinib resistance through maintenance
      of stemness property in HER2-positive breast cancer cells.
AB  - Lapatinib is an inhibitor of human epidermal growth factor receptor 2 (HER2),
      which is overexpressed in 20-25% of breast cancers. Clinically, lapatinib has
      shown promising benefits for HER2-positive breast cancer patients; however,
      patients eventually acquire resistance, limiting its long-term use. In a previous
      study, we found that interleukin-6 (IL-6) production was increased in acquired
      lapatinib-resistant HER2-positive breast cancer cells. In the present study, we
      confirmed that lapatinib-resistant cells had elevated IL-6 expression and also
      maintained both stemness population and property. The increase in IL-6 was
      required for stemness property maintenance, which was mediated primarily through
      the activation of signal transducer and activator of transcription 3 (STAT3).
      Blocking IL-6 activity reduced spheroid formation, cell viability and
      subsequently overcame lapatinib resistance, whereas stimulation of IL-6 rendered
      parental cells more resistant to lapatinib-induced cytotoxicity. These results
      point to a novel mechanism underlying lapatinib resistance and provide a
      potential strategy to overcome resistance via IL-6 inhibition.

PMID- 27694694
TI  - Pharmacokinetics of intravenous peramivir in the airway epithelial lining fluid
      of healthy volunteers.
AB  - BACKGROUND: Some subtypes of influenza virus, such as H5N1 and H7N9, cause severe
      viral pneumonia, for which the intraluminal concentration of the anti-influenza
      agent in the airway is critical. However, the pharmacokinetics of peramivir, the
      only available injectable neuraminidase inhibitor formulation, in the airway
      epithelial lining fluid (ELF) remains unclear. In this study, we aimed to
      determine the time course of peramivir in the pharyngeal ELF, bronchial ELF and
      plasma of healthy volunteers using bronchoscopic microsampling technique.
      METHODS: Six healthy volunteers were studied. After baseline plasma sampling, 0.3
      g peramivir was intravenously injected over 0.5 h. ELF was obtained from the
      upper and lower airways using bronchoscopic microsampling at the end of the
      infusion (0.5 h) and after 1.0, 1.5, 2.0, 2.5, 3.0, 4.0 and 5.0 h. The
      concentrations of peramivir in the ELFs and in the plasma were quantified by
      LC/MS/MS analysis. RESULTS: The mean maximum concentration (Cmax) in pharyngeal
      ELF, bronchial ELF and plasma was 1.20 +/-0.42, 9.60 +/-2.30 and 50.52 +/-17.51
      ng/ml, respectively. The penetration ratio at Cmax in pharyngeal and bronchial
      ELFs was 2.4 and 19.0, respectively. The ratio of the area under the curve from 0
      to infinity in pharyngeal and bronchial ELFs was 4.8 and 39.1 mg*min/l,
      respectively. CONCLUSIONS: The time course of peramivir concentration in the ELFs
      revealed that concentrations above the 50% inhibitory concentration value of
      influenza were achieved in the upper and lower airways. Therefore, peramivir
      could be an important treatment option for influenza viral pneumonia.

PMID- 27694692
TI  - Inhibition of insulin-like growth factor II (IGF-II)-dependent cell growth by
      multidentate pentamannosyl 6-phosphate-based ligands targeting the mannose 6
      phosphate/IGF-II receptor.
AB  - The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) binds
      M6P-capped ligands and IGF-II at different binding sites within the ectodomain
      and mediates ligand internalization and trafficking to the lysosome. Multivalent
      M6P-based ligands can cross-bridge the M6P/IGF2R, which increases the rate of
      receptor internalization, permitting IGF-II binding as a passenger ligand and
      subsequent trafficking to the lysosome, where the IGF-II is degraded. This unique
      feature of the receptor may be exploited to design novel therapeutic agents
      against IGF-II-dependent cancers that will lead to decreased bioavailable IGF-II
      within the tumor microenvironment. We have designed a panel of M6P-based ligands
      that bind to the M6P/IGF2R with high affinity in a bivalent manner and cause
      decreased cell viability. We present evidence that our ligands bind through the
      M6P-binding sites of the receptor and facilitate internalization and degradation
      of IGF-II from conditioned medium to mediate this cellular response. To our
      knowledge, this is the first panel of synthetic bivalent ligands for the
      M6P/IGF2R that can take advantage of the ligand-receptor interactions of the
      M6P/IGF2R to provide proof-of-principle evidence for the feasibility of novel
      chemotherapeutic agents that decrease IGF-II-dependent growth of cancer cells.

PMID- 27694695
TI  - Bipolar resistive switching in YMnO3/Nb:SrTiO3 pn-heterojunctions.
AB  - Resistively switching oxides are promising materials for use in electronic
      applications such as nonvolatile memories, logic gates, and artificial synapses.
      This work presents the bipolar resistive switching (BRS) in YMnO3/Nb:SrTiO3 pn
      heterojunctions. A thermally driven electroforming process is required prior to
      the observed BRS. Results indicate that the BRS in YMnO3/Nb:SrTiO3 originates
      from the combined effects of charge trapping and detrapping processes along with
      the electro-migration of charged point defects in the depletion layer of the pn
      heterojunction. It is shown that the built-in voltage of the pn-heterojunctions
      can be tuned by the oxygen partial pressure during growth of the YMnO3 thin film
      and impacts the working parameters of the resistively switching cell. This study
      provides a guideline for material engineering of bipolar resistive switches based
      on pn-heterojunctions.

PMID- 27694696
TI  - The impact of x-ray tube stabilization on localized radiation dose in axial CT
      scans: initial results in CTDI phantoms.
AB  - Rise, fall, and stabilization of the x-ray tube output occur immediately before
      and after data acquisition on some computed tomography (CT) scanners and are
      believed to contribute additional dose to anatomy facing the x-ray tube when it
      powers on or off. In this study, we characterized the dose penalty caused by
      additional radiation exposure during the rise, stabilization, and/or fall time
      (referred to as overscanning). A 32 cm CT dose-index (CTDI) phantom was scanned
      on three CT scanners: GE Healthcare LightSpeed VCT, GE Healthcare Discovery CT750
      HD, and Siemens Somatom Definition Flash. Radiation exposure was detected for
      various x-ray tube start acquisition angles using a 10 cm pencil ionization
      chamber placed in the peripheral chamber hole at the phantom's 12 o'clock
      position. Scan rotation time, ionization chamber location, phantom diameter, and
      phantom centering were varied to quantify their effects on the dose penalty
      caused by overscanning. For 1 s single, axial rotations, CTDI at the 12 o'clock
      chamber position (CTDI100, 12:00) was 6.1%, 4.0%, and 4.4% higher when the start
      angle of the x-ray tube was aligned at the top of the gantry (12 o'clock) versus
      when the start angle was aligned at 9 o'clock for the Siemens Flash, GE CT750 HD,
      and GE VCT scanner, respectively. For the scanners' fastest rotation times (0.285
      s for the Siemens and 0.4 s for both GE scanners), the dose penalties increased
      to 22.3%, 10.7%, and 10.5%, respectively, suggesting a trade-off between rotation
      speed and the dose penalty from overscanning. In general, overscanning was shown
      to have a greater radiation dose impact for larger diameter phantoms, shorter
      rotation times, and to peripheral phantom locations. Future research is necessary
      to determine an appropriate method for incorporating the localized dose penalty
      from overscanning into standard dose metrics, as well as to assess the impact on
      organ dose.

PMID- 27694697
TI  - Unipolar resistive switching and tunneling oscillations in isolated Si-SiO x core
      shell nanostructure.
AB  - Unipolar resistive switching (URS) is observed in isolated Si-SiO x core-shell
      nanostructures. I-V characteristics recorded by a conductive atomic force
      microscope tip show SET and RESET processes with self compliance behavior.
      Hopping of carriers through defect states in the high resistance state (HRS) and
      space charge limited conduction in the low resistance state (LRS) are found to be
      the dominant carrier transport mechanisms in Si-SiO x core-shell nanostructures.
      URS between LRS and HRS may be attributed to the transition between hydrogen
      bridge (Si-H-Si) and hydrogen doublet (Si-HH-Si) defects. During RESET process,
      charge carriers tunnel through the nanostructure giving rise to oscillatory
      conduction.

PMID- 27694698
TI  - Selective in situ potential-assisted SAM formation on multi electrode arrays.
AB  - The selective modification of individual components in a biosensor array is
      challenging. To address this challenge, we present a generalizable approach to
      selectively modify and characterize individual gold surfaces in an array, in an
      in situ manner. This is achieved by taking advantage of the potential dependent
      adsorption/desorption of surface-modified organic molecules. Control of the
      applied potential of the individual sensors in an array where each acts as a
      working electrode provides differential derivatization of the sensor surfaces. To
      demonstrate this concept, two different self-assembled monolayer (SAM)-forming
      electrochemically addressable omega-ferrocenyl alkanethiols (C11) are chemisorbed
      onto independent but spatially adjacent gold electrodes. The ferrocene
      alkanethiol does not chemisorb onto the surface when the applied potential is
      cathodic relative to the adsorption potential and the electrode remains
      underivatized. However, applying potentials that are modestly positive relative
      to the adsorption potential leads to extensive coverage within 10 min. The
      resulting SAM remains in a stable state while held at potentials <200 mV above
      the adsorption potential. In this state, the chemisorbed SAM does not
      significantly desorb nor do new ferrocenylalkythiols adsorb. Using three set
      applied potentials provides for controlled submonolayer alkylthiol marker
      coverage of each independent gold electrode. These three applied potentials are
      dependent upon the specifics of the respective adsorbate. Characterization of the
      ferrocene-modified electrodes via cyclic voltammetry demonstrates that each
      specific ferrocene marker is exclusively adsorbed to the desired target
      electrode.

PMID- 27694699
TI  - Study of mechanical behavior of AFM silicon tips under mechanical load.
AB  - In this paper we address critical issues concerning calibration of AFM based
      methods used for nanoscale mechanical characterization of materials. It has been
      shown that calibration approaches based on macroscopic models for contact
      mechanics may yield excellent results in terms of the indentation modulus of the
      sample, but fail to provide a comprehensive and actual information concerning the
      tip-sample contact radius or the mechanical properties of the tip. Explanations
      for the severely reduced indentation modulus of the tip included the inadequacies
      of the models used for calculations of the tip-sample contact stiffness,
      discrepancies in the actual and ideal shape of the tip, presence of the amorphous
      silicon phase within the silicon tip, as well as negligence of the actual size of
      the stress field created in the tip during elastic interactions. To clarify these
      issues, we investigated the influence of the mechanical load applied to four AFM
      silicon tips on their crystalline state by exposing them to systematically
      increasing loads, evaluating the character of the tip-sample interactions via the
      load-unload stiffness curves, and assessing the state of the tips from HR-TEM
      images. The results presented in this paper were obtained in a series of
      relatively simple and basic atomic force acoustic microscopy (AFAM) experiments.
      The novel combination of TEM imaging of the AFM tips with the analysis of the
      load-unload stiffness curves gave us a detailed insight into their mechanical
      behavior under load conditions. We were able to identify the limits for the
      elastic interactions, as well as the hallmarks for phase transformation and
      dislocation formation and movement. The comparison of the physical dimensions of
      the AFM tips, geometry parameters determined from the values of the contact
      stiffness, and the information on the crystalline state of the tips allowed us a
      better understanding of the nanoscale contact.

PMID- 27694700
TI  - Optimization-based image reconstruction with artifact reduction in C-arm CBCT.
AB  - We investigate an optimization-based reconstruction, with an emphasis on image
      artifact reduction, from data collected in C-arm cone-beam computed tomography
      (CBCT) employed in image-guided interventional procedures. In the study, an image
      to be reconstructed is formulated as a solution to a convex optimization program
      in which a weighted data divergence is minimized subject to a constraint on the
      image total variation (TV); a data-derivative fidelity is introduced in the
      program specifically for effectively suppressing dominant, low-frequency data
      artifact caused by, e.g. data truncation; and the Chambolle-Pock (CP) algorithm
      is tailored to reconstruct an image through solving the program. Like any other
      reconstructions, the optimization-based reconstruction considered depends upon
      numerous parameters. We elucidate the parameters, illustrate their determination,
      and demonstrate their impact on the reconstruction. The optimization-based
      reconstruction, when applied to data collected from swine and patient subjects,
      yields images with visibly reduced artifacts in contrast to the reference
      reconstruction, and it also appears to exhibit a high degree of robustness
      against distinctively different anatomies of imaged subjects and scanning
      conditions of clinical significance. Knowledge and insights gained in the study
      may be exploited for aiding in the design of practical reconstructions of truly
      clinical-application utility.

PMID- 27694701
TI  - Multiresolution iterative reconstruction in high-resolution extremity cone-beam
      CT.
AB  - Application of model-based iterative reconstruction (MBIR) to high resolution
      cone-beam CT (CBCT) is computationally challenging because of the very fine
      discretization (voxel size  <100 um) of the reconstructed volume. Moreover,
      standard MBIR techniques require that the complete transaxial support for the
      acquired projections is reconstructed, thus precluding acceleration by
      restricting the reconstruction to a region-of-interest. To reduce the
      computational burden of high resolution MBIR, we propose a multiresolution
      penalized-weighted least squares (PWLS) algorithm, where the volume is
      parameterized as a union of fine and coarse voxel grids as well as selective
      binning of detector pixels. We introduce a penalty function designed to
      regularize across the boundaries between the two grids. The algorithm was
      evaluated in simulation studies emulating an extremity CBCT system and in a
      physical study on a test-bench. Artifacts arising from the mismatched
      discretization of the fine and coarse sub-volumes were investigated. The fine
      grid region was parameterized using 0.15 mm voxels and the voxel size in the
      coarse grid region was varied by changing a downsampling factor. No significant
      artifacts were found in either of the regions for downsampling factors of up to
      4*. For a typical extremities CBCT volume size, this downsampling corresponds to
      an acceleration of the reconstruction that is more than five times faster than a
      brute force solution that applies fine voxel parameterization to the entire
      volume. For certain configurations of the coarse and fine grid regions, in
      particular when the boundary between the regions does not cross high attenuation
      gradients, downsampling factors as high as 10*  can be used without introducing
      artifacts, yielding a ~50*  speedup in PWLS. The proposed multiresolution
      algorithm significantly reduces the computational burden of high resolution
      iterative CBCT reconstruction and can be extended to other applications of MBIR
      where computationally expensive, high-fidelity forward models are applied only to
      a sub-region of the field-of-view.

PMID- 27694702
TI  - LET-dependent radiosensitization effects of gold nanoparticles for proton
      irradiation.
AB  - The development of new modalities and protocols is of major interest to improve
      the outcome of cancer treatment. Given the appealing physical properties of
      protons and the emerging evidence of biological relevance of the use of gold
      nanoparticles (GNPs), the radiosensitization effects of GNPs (5 or 10 nm) have
      been investigated in vitro in combination with a proton beam of different linear
      energy transfer (LET). After the incubation with GNPs for 24 h, nanoparticles
      were observed in the cytoplasm of A431 cells exposed to 10 nm GNPs, and in the
      cytoplasm as well as the nucleus of cells exposed to 5 nm GNPs. Cell uptake of
      0.05 mg ml-1 of GNPs led to 0.78 pg Au/cell and 0.30 pg Au/cell after 24 h
      incubation for 10 and 5 nm GNPs respectively. A marked radiosensitization effect
      of GNPs was observed with 25 keV MUm-1 protons, but not with 10 keV MUm-1
      protons. This effect was more pronounced for 10 nm GNPs than for 5 nm GNPs. By
      using a radical scavenger, a major role of reactive oxygen species in the
      amplification of the death of irradiated cell was identified. All together, these
      results open up novel perspectives for using high-Z metallic NPs in
      protontherapy.

PMID- 27694703
TI  - The effect of temperature dependent tissue parameters on acoustic radiation force
      induced displacements.
AB  - Multiple ultrasound elastography techniques rely on acoustic radiation force
      (ARF) in monitoring high-intensity focused ultrasound (HIFU) therapy. However,
      ARF is dependent on tissue attenuation and sound speed, both of which are also
      known to change with temperature making the therapy monitoring more challenging.
      Furthermore, the viscoelastic properties of tissue are also temperature
      dependent, which affects the displacements induced by ARF. The aim of this study
      is to quantify the temperature dependent changes in the acoustic and viscoelastic
      properties of liver and investigate their effect on ARF induced displacements by
      using both experimental methods and simulations. Furthermore, the temperature
      dependent viscoelastic properties of liver are experimentally measured over a
      frequency range of 0.1-200 Hz at temperatures reaching 80  degrees C, and both
      conventional and fractional Zener models are used to fit the data. The fractional
      Zener model was found to fit better with the experimental viscoelasticity data
      with respect to the conventional model with up to two orders of magnitude lower
      sum of squared errors (SSE). The characteristics of experimental displacement
      data were also seen in the simulations due to the changes in attenuation
      coefficient and lesion development. At low temperatures before thermal ablation,
      attenuation was found to affect the displacement amplitude. At higher
      temperature, the decrease in displacement amplitude occurs approximately at 60-70
      degrees C due to the combined effect of viscoelasticity changes and lesion
      growth overpowering the effect of attenuation. The results suggest that it is
      necessary to monitor displacement continuously during HIFU therapy in order to
      ascertain when ablation occurs.

PMID- 27694704
TI  - Image reconstruction algorithm for optically stimulated luminescence 2D dosimetry
      using laser-scanned Al2O3:C and Al2O3:C,Mg films.
AB  - The objective of this work was to develop an image reconstruction algorithm for
      2D dosimetry using Al2O3:C and Al2O3:C,Mg optically stimulated luminescence (OSL)
      films imaged using a laser scanning system. The algorithm takes into account
      parameters associated with detector properties and the readout system. Pieces of
      Al2O3:C films (~8 mm  *  8 mm  *  125 um) were irradiated and used to simulate
      dose distributions with extreme dose gradients (zero and non-zero dose regions).
      The OSLD film pieces were scanned using a custom-built laser-scanning OSL reader
      and the data obtained were used to develop and demonstrate a dose reconstruction
      algorithm. The algorithm includes corrections for: (a) galvo hysteresis, (b)
      photomultiplier tube (PMT) linearity, (c) phosphorescence, (d) 'pixel bleeding'
      caused by the 35 ms luminescence lifetime of F-centers in Al2O3, (e) geometrical
      distortion inherent to Galvo scanning system, and (f) position dependence of the
      light collection efficiency. The algorithm was also applied to 6.0 cm  *  6.0 cm 
      *  125 MUm or 10.0 cm  *  10.0 cm  *  125 um Al2O3:C and Al2O3:C,Mg films exposed
      to megavoltage x-rays (6 MV) and 12C beams (430 MeV u-1). The results obtained
      using pieces of irradiated films show the ability of the image reconstruction
      algorithm to correct for pixel bleeding even in the presence of extremely sharp
      dose gradients. Corrections for geometric distortion and position dependence of
      light collection efficiency were shown to minimize characteristic limitations of
      this system design. We also exemplify the application of the algorithm to more
      clinically relevant 6 MV x-ray beam and a 12C pencil beam, demonstrating the
      potential for small field dosimetry. The image reconstruction algorithm described
      here provides the foundation for laser-scanned OSL applied to 2D dosimetry.

PMID- 27694705
TI  - EVolution: an edge-based variational method for non-rigid multi-modal image
      registration.
AB  - Image registration is part of a large variety of medical applications including
      diagnosis, monitoring disease progression and/or treatment effectiveness and,
      more recently, therapy guidance. Such applications usually involve several
      imaging modalities such as ultrasound, computed tomography, positron emission
      tomography, x-ray or magnetic resonance imaging, either separately or combined.
      In the current work, we propose a non-rigid multi-modal registration method
      (namely EVolution: an edge-based variational method for non-rigid multi-modal
      image registration) that aims at maximizing edge alignment between the images
      being registered. The proposed algorithm requires only contrasts between
      physiological tissues, preferably present in both image modalities, and assumes
      deformable/elastic tissues. Given both is shown to be well suitable for non-rigid
      co-registration across different image types/contrasts (T1/T2) as well as
      different modalities (CT/MRI). This is achieved using a variational scheme that
      provides a fast algorithm with a low number of control parameters. Results
      obtained on an annotated CT data set were comparable to the ones provided by
      state-of-the-art multi-modal image registration algorithms, for all tested
      experimental conditions (image pre-filtering, image intensity variation, noise
      perturbation). Moreover, we demonstrate that, compared to existing approaches,
      our method possesses increased robustness to transient structures (i.e. that are
      only present in some of the images).

PMID- 27694706
TI  - Automatic landmark generation for deformable image registration evaluation for 4D
      CT images of lung.
AB  - Deformable image registration (DIR) has become a common tool in medical imaging
      across both diagnostic and treatment specialties, but the methods used offer
      varying levels of accuracy. Evaluation of DIR is commonly performed using
      manually selected landmarks, which is subjective, tedious and time consuming. We
      propose a semi-automated method that saves time and provides accuracy comparable
      to manual selection. Three landmarking methods including manual (with two
      independent observers), scale invariant feature transform (SIFT), and SIFT with
      manual editing (SIFT-M) were tested on 10 thoracic 4DCT image studies
      corresponding to the 0% and 50% phases of respiration. Results of each method
      were evaluated against a gold standard (GS) landmark set comparing both mean and
      proximal landmark displacements. The proximal method compares the local
      deformation magnitude between a test landmark pair and the closest GS pair.
      Statistical analysis was done using an intra class correlation (ICC) between test
      and GS displacement values. The creation time per landmark pair was 22, 34, 2.3,
      and 4.3 s for observers 1 and 2, SIFT, and SIFT-M methods respectively. Across 20
      lungs from the 10 CT studies, the ICC values between the GS and observer 1 and 2,
      SIFT, and SIFT-M methods were 0.85, 0.85, 0.84, and 0.82 for mean lung
      deformation, and 0.97, 0.98, 0.91, and 0.96 for proximal landmark deformation,
      respectively. SIFT and SIFT-M methods have an accuracy that is comparable to
      manual methods when tested against a GS landmark set while saving 90% of the
      time. The number and distribution of landmarks significantly affected the
      analysis as manifested by the different results for mean deformation and proximal
      landmark deformation methods. Automatic landmark methods offer a promising
      alternative to manual landmarking, if the quantity, quality and distribution of
      landmarks can be optimized for the intended application.

PMID- 27694708
TI  - Sharpening peripheral dose gradient via beam number enhancement from patient head
      tilt for stereotactic brain radiosurgery.
AB  - Sharp dose fall-off is the hallmark of brain radiosurgery for the purpose of
      delivering high dose radiation to the target while minimizing peripheral dose to
      regional normal brain tissue. In this study, a technique was developed to enhance
      the peripheral dose gradient by magnifying the total number of beams focused
      toward each isocenter through pre-programmed patient head tilting. This technique
      was tested in clinical settings on a dedicated brain radiosurgical system (GKPFX,
      Gamma Knife Perfexion, Elekta Oncology) by comparing dosimetry as well as
      delivery efficiency for 20 radiosurgical cases previously treated with the
      system. The 3-fold beam number enhancement (BNE) treatment plans were found to
      produce nearly identical target volume coverage (absolute value  <  0.5%, P  > 
      0.2) and dose conformity (BNE CI  =  1.41  +/-  0.22 versus 1.41  +/-  0.11, P  >
      0.99) as the original treatment plans. The total beam-on time for the 3-fold BNE
      treatment plans were also found to be comparable (<0.5 min or 2%) with those of
      the original treatment plans for all the cases. However, BNE treatment plans
      significantly improved the mean gradient index (BNE GI  =  2.94  +/-  0.27 versus
      original GI  =  2.98  +/-  0.28 P  <  0.0001) and low-level isodose volumes, e.g.
      20-50% prescribed isodose volumes, by 1.7%-3.9% (P  <  0.03). With further 4-5
      fold increase in the total number of beams, the absolute gradient index can
      decrease by as much as  -0.5 in absolute value or  -20% for a treatment. In
      conclusion, BNE via patient head tilt has been demonstrated to be a clinically
      suitable and efficient technique for physically sharpening the peripheral dose
      gradient for brain radiosurgery.

PMID- 27694707
TI  - Molecular image-directed biopsies: improving clinical biopsy selection in
      patients with multiple tumors.
AB  - Site selection for image-guided biopsies in patients with multiple lesions is
      typically based on clinical feasibility and physician preference. This study
      outlines the development of a selection algorithm that, in addition to clinical
      requirements, incorporates quantitative imaging data for automatic identification
      of candidate lesions for biopsy. The algorithm is designed to rank potential
      targets by maximizing a lesion-specific score, incorporating various criteria
      separated into two categories: (1) physician-feasibility category including
      physician-preferred lesion location and absolute volume scores, and (2) imaging
      based category including various modality and application-specific metrics. This
      platform was benchmarked in two clinical scenarios, a pre-treatment setting and
      response-based setting using imaging from metastatic prostate cancer patients
      with high disease burden (multiple lesions) undergoing conventional treatment and
      receiving whole-body [18F]NaF PET/CT scans pre- and mid-treatment. Targeting of
      metastatic lesions was robust to different weighting ratios and candidacy for
      biopsy was physician confirmed. Lesion ranked as top targets for biopsy remained
      so for all patients in pre-treatment and post-treatment biopsy selection after
      sensitivity testing was completed for physician-biased or imaging-biased
      scenarios. After identifying candidates, biopsy feasibility was evaluated by a
      physician and confirmed for 90% (32/36) of high-ranking lesions, of which all top
      choices were confirmed. The remaining cases represented lesions with high
      anatomical difficulty for targeting, such as proximity to sciatic nerve. This
      newly developed selection method was successfully used to quantitatively identify
      candidate lesions for biopsies in patients with multiple lesions. In a
      prospective study, we were able to successfully plan, develop, and implement this
      technique for the selection of a pre-treatment biopsy location.

PMID- 27694710
TI  - Structural instability and phase co-existence driven non-Gaussian resistance
      fluctuations in metal nanowires at low temperatures.
AB  - We report a detailed experimental study of the resistance fluctuations measured
      at low temperatures in high quality metal nanowires ranging in diameter from 15
      200 nm. The wires exhibit co-existing face-centered-cubic and 4H hcp phases of
      varying degrees as determined from the x-ray diffraction data. We observe the
      appearance of a large non-Gaussian noise for nanowires of diameter smaller than
      50 nm over a certain temperature range around ~30 K. The diameter range ~30 nm,
      where the noise has maxima coincides with the maximum volume fraction of the co
      existing 4H hcp phase thus establishing a strong link between the fluctuation and
      the phase co-existence. The resistance fluctuation in the same temperature range
      also shows a deviation of [Formula: see text] behavior at low frequency with
      appearance of single frequency Lorentzian type contribution in the spectral power
      density. The fluctuations are thermally activated with an activation energy
      [Formula: see text] meV, which is of same order as the activation energy of
      creation of stacking fault in FCC metals that leads to the co-existing
      crystallographic phases. Combining the results of crystallographic studies of the
      nanowires and analysis of the resistance fluctuations we could establish the
      correlation between the appearance of the large resistance noise and the onset of
      phase co-existence in these nanowires.

PMID- 27694709
TI  - A novel anthropomorphic flow phantom for the quantitative evaluation of prostate
      DCE-MRI acquisition techniques.
AB  - A novel anthropomorphic flow phantom device has been developed, which can be used
      for quantitatively assessing the ability of magnetic resonance imaging (MRI)
      scanners to accurately measure signal/concentration time-intensity curves (CTCs)
      associated with dynamic contrast-enhanced (DCE) MRI. Modelling of the complex
      pharmacokinetics of contrast agents as they perfuse through the tumour capillary
      network has shown great promise for cancer diagnosis and therapy monitoring.
      However, clinical adoption has been hindered by methodological problems,
      resulting in a lack of consensus regarding the most appropriate acquisition and
      modelling methodology to use and a consequent wide discrepancy in published data.
      A heretofore overlooked source of such discrepancy may arise from measurement
      errors of tumour CTCs deriving from the imaging pulse sequence itself, while the
      effects on the fidelity of CTC measurement of using rapidly-accelerated sequences
      such as parallel imaging and compressed sensing remain unknown. The present work
      aimed to investigate these features by developing a test device in which 'ground
      truth' CTCs were generated and presented to the MRI scanner for measurement,
      thereby allowing for an assessment of the DCE-MRI protocol to accurately measure
      this curve shape. The device comprised a four-pump flow system wherein CTCs
      derived from prior patient prostate data were produced in measurement chambers
      placed within the imaged volume. The ground truth was determined as the mean of
      repeat measurements using an MRI-independent, custom-built optical imaging
      system. In DCE-MRI experiments, significant discrepancies between the ground
      truth and measured CTCs were found for both tumorous and healthy tissue-mimicking
      curve shapes. Pharmacokinetic modelling revealed errors in measured K trans, v e
      and k ep values of up to 42%, 31%, and 50% respectively, following a simple
      variation of the parallel imaging factor and number of signal averages in the
      acquisition protocol. The device allows for the quantitative assessment and
      standardisation of DCE-MRI protocols (both existing and emerging).

PMID- 27694711
TI  - Why is it difficult to wash aphids off from superhydrophobic kale?
AB  - Many varieties of the cabbage family have leaves covered with superhydrophobic
      epicuticular wax, which provides them with self-cleaning characteristics. Since
      the wax also lowers insect adhesion, rinsing of the leaves with water should be
      an effective way of removing the insects. Conversely, we report that
      superhydrophobicity of tuscan kale increases resistance of aphids to hydrodynamic
      removal. The exterior surface of the insects is also superhydrophobic and acts as
      an extension of the leaf's surface. As a result even at moderate impact
      velocities impinging water drops cannot penetrate under the pests. Consequently,
      liquid impact aids the insect's adhesion by increasing the normal compressive
      forces they experience. We show that on a hydrophilic arugula leaf this mechanism
      is absent, and aphids can be easily washed off with water, as it is able to
      penetrate underneath them. As for removal of aphids from Tuscan kale, we show
      that lower surface tension liquids, such as oils and soapy water are more
      effective, because they are able to wet both the plant and insect surfaces. We
      also show that aerodynamic removal of aphids consisting of simply exposing the
      invaded leaf to an air flow is most effective.

PMID- 27694713
TI  - A simplified analytical random walk model for proton dose calculation.
AB  - We propose an analytical random walk model for proton dose calculation in a
      laterally homogeneous medium. A formula for the spatial fluence distribution of
      primary protons is derived. The variance of the spatial distribution is in the
      form of a distance-squared law of the angular distribution. To improve the
      accuracy of dose calculation in the Bragg peak region, the energy spectrum of the
      protons is used. The accuracy is validated against Monte Carlo simulation in
      water phantoms with either air gaps or a slab of bone inserted. The algorithm
      accurately reflects the dose dependence on the depth of the bone and can deal
      with small-field dosimetry. We further applied the algorithm to patients' cases
      in the highly heterogeneous head and pelvis sites and used a gamma test to show
      the reasonable accuracy of the algorithm in these sites. Our algorithm is fast
      for clinical use.

PMID- 27694712
TI  - Recent developments and comprehensive evaluations of a GPU-based Monte Carlo
      package for proton therapy.
AB  - Monte Carlo (MC) simulation is commonly considered as the most accurate dose
      calculation method for proton therapy. Aiming at achieving fast MC dose
      calculations for clinical applications, we have previously developed a graphics
      processing unit (GPU)-based MC tool, gPMC. In this paper, we report our recent
      updates on gPMC in terms of its accuracy, portability, and functionality, as well
      as comprehensive tests on this tool. The new version, gPMC v2.0, was developed
      under the OpenCL environment to enable portability across different computational
      platforms. Physics models of nuclear interactions were refined to improve
      calculation accuracy. Scoring functions of gPMC were expanded to enable tallying
      particle fluence, dose deposited by different particle types, and dose-averaged
      linear energy transfer (LETd). A multiple counter approach was employed to
      improve efficiency by reducing the frequency of memory writing conflict at
      scoring. For dose calculation, accuracy improvements over gPMC v1.0 were observed
      in both water phantom cases and a patient case. For a prostate cancer case
      planned using high-energy proton beams, dose discrepancies in beam entrance and
      target region seen in gPMC v1.0 with respect to the gold standard tool for proton
      Monte Carlo simulations (TOPAS) results were substantially reduced and gamma test
      passing rate (1%/1 mm) was improved from 82.7%-93.1%. The average relative
      difference in LETd between gPMC and TOPAS was 1.7%. The average relative
      differences in the dose deposited by primary, secondary, and other heavier
      particles were within 2.3%, 0.4%, and 0.2%. Depending on source proton energy and
      phantom complexity, it took 8-17 s on an AMD Radeon R9 290x GPU to simulate
      [Formula: see text] source protons, achieving less than [Formula: see text]
      average statistical uncertainty. As the beam size was reduced from 10  *  10 cm2
      to 1  *  1 cm2, the time on scoring was only increased by 4.8% with eight
      counters, in contrast to a 40% increase using only one counter. With the OpenCL
      environment, the portability of gPMC v2.0 was enhanced. It was successfully
      executed on different CPUs and GPUs and its performance on different devices
      varied depending on processing power and hardware structure.

PMID- 27694714
TI  - Review of plastic and liquid scintillation dosimetry for photon, electron, and
      proton therapy.
AB  - While scintillation dosimetry has been around for decades, the need for a
      dosimeter tailored to the reality of modern radiation therapy-in particular a
      real-time, water-equivalent, energy-independent dosimeter with high spatial
      resolution-has generated renewed interest in scintillators over the last 10
      years. With the advent of at least one commercial plastic scintillation dosimeter
      and the ever-growing scientific literature on this subject, this topical review
      is intended to provide the medical physics community with a wide overview of
      scintillation physics, related optical concepts, and applications of plastic
      scintillation dosimetry.

PMID- 27694715
TI  - A correction scheme for a simplified analytical random walk model algorithm of
      proton dose calculation in distal Bragg peak regions.
AB  - The lateral homogeneity assumption is used in most analytical algorithms for
      proton dose, such as the pencil-beam algorithms and our simplified analytical
      random walk model. To improve the dose calculation in the distal fall-off region
      in heterogeneous media, we analyzed primary proton fluence near heterogeneous
      media and propose to calculate the lateral fluence with voxel-specific Gaussian
      distributions. The lateral fluence from a beamlet is no longer expressed by a
      single Gaussian for all the lateral voxels, but by a specific Gaussian for each
      lateral voxel. The voxel-specific Gaussian for the beamlet of interest is
      calculated by re-initializing the fluence deviation on an effective surface where
      the proton energies of the beamlet of interest and the beamlet passing the voxel
      are the same. The dose improvement from the correction scheme was demonstrated by
      the dose distributions in two sets of heterogeneous phantoms consisting of
      cortical bone, lung, and water and by evaluating distributions in example
      patients with a head-and-neck tumor and metal spinal implants. The dose
      distributions from Monte Carlo simulations were used as the reference. The
      correction scheme effectively improved the dose calculation accuracy in the
      distal fall-off region and increased the gamma test pass rate. The extra
      computation for the correction was about 20% of that for the original algorithm
      but is dependent upon patient geometry.

PMID- 27694716
TI  - Scatter free imaging for the improvement of breast cancer detection in
      mammography.
AB  - In mammography, the reduction of scattered x-rays is vital due to the low
      contrast or small dimension of the details that are searched for. The typical
      method of doing so in current conventional mammography is the anti-scatter grid.
      The disadvantage of this method is the absorption of a proportion of the primary
      beam and therefore an increase in dose is required to compensate for the loss of
      counts. An alternative method is proposed, using quasi-monochromatic beams and a
      pixellated spectroscopic detector. As Compton-scattered x-rays lose energy in the
      scattering process, they are detected at a lower energy in the spectrum.
      Therefore the spectrum can be windowed around the monochromatic energy peak,
      removing the scattered x-rays from the image. The work presented here shows
      contrast improvement of up to 50% and contrast to noise ratio improvements of
      around 20% for scatter free imaging in comparison to full spectrum imaging.
      Contrast improvements of around 45% were found when comparing scatter free images
      to conventional polychromatic imaging for both the low contrast test object and
      the Rachel anthropomorphic breast phantom.

PMID- 27694718
TI  - Dielectric characterization of healthy and malignant colon tissues in the 0.5-18
      GHz frequency band.
AB  - Several reports over the last few decades have shown that the dielectric
      properties of healthy and malignant tissues of the same body organ usually show
      different values. However, no intensive dielectric studies of human colon tissue
      have been performed, despite colon cancer's being one of the most common types of
      cancer in the world. In order to provide information regarding this matter, a
      dielectric characterization of healthy and malignant colon tissues is presented.
      Measurements are performed on ex vivo surgery samples obtained from 20 patients,
      using an open-ended coaxial probe in the 0.5-18 GHz frequency band. Results show
      that the dielectric constant of colon cancerous tissue is 8.8% higher than that
      of healthy tissues (p  =  0.002). Besides, conductivity is about 10.6% higher,
      but in this case measurements do not have statistical significance (p  =  0.038).
      Performing an analysis per patient, the differences in dielectric constant
      between healthy and malignant tissues appear systematically. Particularized
      results for specific frequencies (500 MHz, 900 MHz, 2.45 GHz, 5 GHz, 8.5 GHz and
      15 GHz) are also reported. The findings have potential application in early-stage
      cancer detection and diagnosis, and can be useful in developing new tools for
      hyperthermia treatments as well as creating electromagnetic models of healthy and
      cancerous tissues.

PMID- 27694717
TI  - An accelerated photo-magnetic imaging reconstruction algorithm based on an
      analytical forward solution and a fast Jacobian assembly method.
AB  - We previously introduced photo-magnetic imaging (PMI), an imaging technique that
      illuminates the medium under investigation with near-infrared light and measures
      the induced temperature increase using magnetic resonance thermometry (MRT).
      Using a multiphysics solver combining photon migration and heat diffusion, PMI
      models the spatiotemporal distribution of temperature variation and recovers high
      resolution optical absorption images using these temperature maps. In this paper,
      we present a new fast non-iterative reconstruction algorithm for PMI. This new
      algorithm uses analytic methods during the resolution of the forward problem and
      the assembly of the sensitivity matrix. We validate our new analytic-based
      algorithm with the first generation finite element method (FEM) based
      reconstruction algorithm previously developed by our team. The validation is
      performed using, first synthetic data and afterwards, real MRT measured
      temperature maps. Our new method accelerates the reconstruction process 30-fold
      when compared to a single iteration of the FEM-based algorithm.

PMID- 27694719
TI  - Effective particle energies for stopping power calculation in radiotherapy
      treatment planning with protons and helium, carbon, and oxygen ions.
AB  - The stopping power ratio (SPR) of body tissues relative to water depends on the
      particle energy. For simplicity, however, most analytical dose planning systems
      do not account for SPR variation with particle energy along the beam's path, but
      rather assume a constant energy for SPR estimation. The range error due to this
      simplification could be indispensable depending on the particle species and the
      assumed energy. This error can be minimized by assuming a suitable energy
      referred to as an 'effective energy' in SPR estimation. To date, however, the
      effective energy has never been investigated for realistic patient geometries. We
      investigated the effective energies for proton, helium-, carbon-, and oxygen-ion
      radiotherapy using volumetric models of the reference male and female phantoms
      provided by the International Commission on Radiological Protection (ICRP). The
      range errors were estimated by comparing the particle ranges calculated when
      particle energy variations were and were not considered. The effective energies
      per nucleon for protons and helium, carbon, and oxygen ions were 70 MeV, 70 MeV,
      131 MeV, and 156 MeV, respectively. Using the determined effective energies, the
      range errors were reduced to  ?0.3 mm for respective particle species. For SPR
      estimation of multiple particle species, an effective energy of 100 MeV is
      recommended, with which the range error is  ?0.5 mm for all particle species.

PMID- 27694720
TI  - Chagas disease prevalence in pregnant women: migration and risk of congenital
      transmission.
AB  - INTRODUCTION: Argentina has been a preferential target for Bolivian immigrants
      for decades. The relatively recent migratory flux includes Germany, France, the
      United States, Australia, Japan, and some Latin American countries. The aim of
      this cross-sectional study was to describe the prevalence of Chagas disease in
      pregnant women, analyzing the Bolivian-specific Chagas prevalence as the main
      contributor of migratory populations from Chagas disease-endemic areas to Buenos
      Aires city, Argentina, and to evaluate the impact of these migrant influxes on
      the process of the "urbanization" of the disease in reference hospital Jose Maria
      Ramos Mejia (JMRM). METHODOLOGY: Overall, 21,332 pregnant women (100%) between 15
      and 49 years of age derived from the public maternity service of JMRMH were
      studied. Serology data was obtained from registered serological diagnosis data,
      consisting of three different serological tests performed at the Public
      Parasitology Unit. RESULTS: Although general prevalence decreased during the
      analyzed period, the specific prevalence of pregnant women from Bolivian origin
      showed a sustained growth during 1983-2013. Solely 5% of the total pregnant women
      population from Bolivia contributed to one third of the total Chagas prevalence.
      CONCLUSIONS: This study showed that a cohort of pregnant women from Bolivia who
      attended JMRMH during the period 1983-2007 constituted a population at risk for
      congenital transmission. Increased migration from endemic areas of Bolivia might
      potentially increase the prevalence of Chagas disease among pregnant women. In
      addition, this study highlights the importance to analyze specific prevalence
      according to endemic areas to determine the profiles of potential hidden
      prevalence.

PMID- 27694721
TI  - Prevalence of cutaneous warts in patients with systemic lupus erythematosus: a
      systematic review.
AB  - The aim of this study was to review and evaluate systematically the scientific
      evidence on the relationship between systemic lupus erythematosus (SLE) and
      cutaneous warts (CW) caused by human papillomavirus (HPV) infection. With strict
      inclusion and exclusion criteria, we extensively searched the PUBMED, BVS
      (Virtual Health Library), and SCOPUS databases for the studies that evaluated the
      prevalence of CW in patients with SLE. Secondary references were additionally
      obtained from the selected articles. Only four articles met the research criteria
      and showed a higher frequency of CW in SLE patients compared to healthy controls.
      One of them highlighted about rheumatoid factor (RF) in the sera of patients with
      SLE and found an inverse correlation between the occurrence of warts and RF
      autoantibody. Moreover, most of the selected articles showed that the presence of
      CW did not correlate with the use of immunosuppressive drugs. Therefore, these
      findings suggest that the prevalence of CW in patients with SLE is probably high
      due to the defects in immune mechanisms, independently of immunosuppressive
      drugs.

PMID- 27694722
TI  - Nosocomial coagulase-negative staphylococci in Belgrade: between Scylla and
      Charybdis.
AB  - INTRODUCTION: Coagulase-negative staphylococci (CoNS) are increasingly resistant
      nosocomial pathogens. We aimed to analyze the prevalence of CoNS isolates in
      clinical settings, the evolution of antimicrobial resistance of CoNS, and
      antibiotic consumption in a hospital. METHODOLOGY: This retrospective cohort
      study was carried out at a tertiary healthcare facility over 17 months.
      Identification of isolated cultures and antibiotic susceptibility testing were
      performed using the Vitek2 system. Of 1,217 isolates, 209 were obtained from 193
      patients who had symptoms of nosocomial infections. Data were analyzed by
      descriptive statistics. Antibiotic consumption in the hospital is expressed in
      defined daily doses/100 patient days. RESULTS: Sixty-one percent of patients were
      admitted to the internal medicine ward, while others were admitted to the
      surgical ward. Forty-four percent of Gram-positive isolates were from wound
      swabs, and 26% were from blood. The predominant Gram-positive bacteria were CoNS.
      Antibiotic resistance of CoNS was highest against beta-lactam antibiotics,
      macrolides, and tetracyclines. Tigecycline, linezolid, and vancomycin produced
      the highest activities against CoNS in in vitro conditions, and consumption of
      linezolid and tigecycline increased in the same period. CONCLUSION: There are
      just a few remaining therapeutic options for the treatment of CoNS according to
      our results; vancomycin, linezolid, and tigecycline might be considered as first
      choice antibiotics, but such a hypothesis should be supported with a
      pharmacoeconomic analysis. Unfortunately, novel antimicrobial agents are still
      unavailable and/or too expensive in developing countries. However, inappropriate
      use of those antibiotics may lead to the rapid development of resistant strains
      in the near future.

PMID- 27694723
TI  - Antimicrobial susceptibility and vaginolysin in Gardnerella vaginalis from
      healthy and bacterial vaginosis diagnosed women.
AB  - INTRODUCTION: Bacterial vaginosis (BV) is a syndrome related to Gardnerella
      vaginalis and is characterized by an imbalance in the vaginal microbiota. This
      work focused on the evaluation of antimicrobial susceptibility patterns and the
      occurrence of the vaginolysin (vly) gene in G. vaginalis isolated from BV and non
      BV patients. METHODOLOGY: The vaginal secretions were collected randomly and
      processed for G. vaginalis isolation. The isolates were presumptively identified
      by beta-hemolysis and oxidase and catalase tests. Polymerase chain reaction (PCR)
      was performed to confirm bacterial identity and to detect the vly gene.
      Antimicrobial susceptibility patterns were determined. RESULTS: Of 89 patients,
      G. vaginalis was isolated from 42 (37 BV and 5 non-BV), and 204 isolates were
      selected (179 from BV and 25 non-BV). The vly gene was detected in all G.
      vaginalis isolated from non-BV women and in 98.3% of the bacteria from BV
      patients. High resistance was observed for ampicillin (54.4%), metronidazole
      (59.8%), tinidazole (60.3%) and secnidazole (71.6%). CONCLUSIONS: Further studies
      are needed to better address the role of G. vaginalis and the vly gene in BV
      pathogenesis.

PMID- 27694724
TI  - Prevalence and multidrug resistance of Escherichia coli from community-acquired
      infections in Lagos, Nigeria.
AB  - INTRODUCTION: The emergence of multidrug resistance (MDR; resistance to >= 2 more
      antimicrobials) in Escherichia coli is of concern due to complications
      encountered in treatment. METHODOLOGY: In this study, prevalence, antimicrobial
      resistance, and genetic characteristics of MDR community isolates of E. coli from
      Lagos, Nigeria were determined. Urine and stool samples were obtained from
      outpatients attending Lagos State hospitals and from animal handlers in
      abattoirs, poultries, and open markets, from December 2012 to July 2013. RESULTS:
      Approximately 50% of urine (200/394) and 88% of stool samples (120/136) were
      positive for E. coli. Based upon beta-lactamase production, a subset of those
      isolates was selected for further study. Of the 22 antimicrobials tested, E. coli
      exhibited resistance to all antimicrobials except amikacin and
      piperacillin/tazobactam. The highest levels of resistance were to tetracycline
      (182/247; 73.7%), trimethoprim/sulfamethoxazole (152/247; 61.5%), and ampicillin
      (147/247; 59.1%). Resistance to the cephalosporins ranged from 1.6%-15% including
      the third- and fourth-generation cephalosporins, cefpodoxime (20/247; 8.1%) and
      cefepime (4/247; 1.6%), respectively. MDR was observed in 69.6% (172/247) of the
      isolates. Forty-eight E. coli resistant to at least five antimicrobials were
      selected for further analysis using pulsed-field gel electrophoresis; seven
      distinct clusters were observed among the diverse patterns. Of the 48 MDR E.
      coli, 30 different sequence types (ST) were detected using multilocus sequence
      typing, including four ST131. CONCLUSIONS: This study demonstrated circulating
      MDR E. coli in the Nigerian community. Monitoring of antimicrobial resistance in
      developing countries is necessary to optimize empiric treatment and the prudent
      use of antimicrobials.

PMID- 27694725
TI  - Biofilm-forming and antimicrobial resistance traits of staphylococci isolated
      from goat dairy plants.
AB  - INTRODUCTION: Biofilm-associated antimicrobial resistance is of increasing
      importance to the maintenance and spread of foodborne pathogens in the food
      industry. This study aimed to investigate the ability to form biofilm and the
      antimicrobial resistance of staphylococci contaminating small-scale goat milk
      dairy plants. METHODOLOGY: Sixty isolates were tested for antimicrobial
      resistance against 20 drugs by the microdilution method. Biofilm-forming traits
      were assessed by the microtiter plate method (MtP), Congo red agar method (CRA),
      and icaD gene detection by polymerase chain reaction (PCR). RESULTS: High
      antimicrobial resistance to ampicillin (60/60; 100%), penicillin G (21/60; 35%),
      and erythromycin (15/60; 25%) was observed, but all isolates were susceptible to
      amoxicillin/K-clavulanate, ceftriaxone, ciprofloxacin, gentamicin, levofloxacin,
      linezolid, and moxifloxacin. No resistance to oxacillin or vancomycin was seen
      among Staphylococcus aureus. Twenty-seven isolates (27/60; 45%) were considered
      to form biofilm according to MtP, and similar biofilm-producing frequencies were
      observed in coagulase-negative staphylococci (CoNS) (20/44; 45.4%) and S. aureus
      (7/16; 43.7%). The icaD gene was observed only in S. aureus isolates. There was
      no association between biofilm production and antimicrobial resistance. A higher
      frequency of biofilm-producing staphylococci was found in isolates from bulk tank
      milk and hand swabs. On the other hand, isolates from pasteurized milk showed
      lower frequency of biofilm formation. CONCLUSIONS: Staphylococci contaminating
      goat dairy plants are potential biofilm producers. The results suggest no
      association between the ability to form biofilm and antimicrobial resistance.

PMID- 27694726
TI  - Seroprevalence of brucellosis in patients with prolonged fever in Bangladesh.
AB  - INTRODUCTION: This study describes the seroprevalence of human brucellosis among
      pyretic patients and detection of Brucella abortus DNA from seropositive pyretic
      patients using real-time polymerase chain reaction (rtPCR) for the first time in
      Bangladesh. METHODOLOGY: Blood samples were collected from 300 pyretic patients
      from October 2007 to May 2008 and subjected to three serological tests: Rose
      Bengal plate test (RBT), standard tube agglutination test (STAT), and indirect
      enzyme-linked immunosorbent assay (iELISA). Risk factors were identified by
      multivariate Firth's logistic regression analysis. Brucella genus (BCSP31) and
      species-specific (IS711) rtPCR were applied to six human sera samples. RESULTS:
      The seroprevalence of brucellosis among pyretic patients was estimated to be 2.0%
      (95% confidence interval [CI]: 0.74-4.30). The odds of brucellosis seropositivity
      were 8.9 (95% CI: 1.26-63.0) times higher in pyretic patients who handled goats
      than those who handled only cattle, whereas the odds of brucellosis
      seropositivity were 9.7 (95% CI: 1.28-73.68) times higher in pyretic patients who
      had backache compared to those without backache. B. abortus DNA was amplified
      from all six human sera that tested positive by RBT, STAT, and iELISA. As the
      agreement between the tests was very strong, RBT is recommended as a screening
      test for the diagnosis of human brucellosis in Bangladesh because it is easier to
      use, cheaper, and faster. CONCLUSIONS: Brucellosis among pyretic patients is
      common, and B. abortus is responsible for brucellosis in such patients. Pyretic
      patients who handle goats and those with backaches should be screened for
      brucellosis.

PMID- 27694727
TI  - Multidrug-resistant ESBL-producing Enterobacteriaceae and associated risk factors
      in community infants in Lebanon.
AB  - INTRODUCTION: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL
      PE) infections are a growing threat to children, and the treatment of these
      infections becomes more and more challenging. A huge reservoir for ESBLs in the
      community is the fecal flora of children. This study investigates the rectal
      colonization, associated risk factors, antimicrobial susceptibility, and
      molecular characterization of ESBL-PE in Lebanese community infants. METHODOLOGY:
      A total of 117 rectal swabs were taken from healthy infants between 1 and 12
      months of age. Detection of ESBLs was carried out using the double-disk synergy
      test, combination-disk method, and multiplex polymerase chain reaction (PCR). A
      questionnaire about the infant's history and risk factors for carrying ESBL-PE
      was administered. RESULTS: In total, 58 (49.6%) of 117 participants were ESBL-PE
      carriers. Some significant important risk factors for colonization in this study
      were male gender, hospital birth, caesarean delivery, and being formula-fed.
      Observed decrease in colonization rate was associated with intimate hygiene
      habits. Carriers of multiple bla genes were the most common. CTX-M type was the
      major harbored, gene and CTX-M-9 was the most predominant, followed by CTX-M-15
      type. CONCLUSIONS: To the best of our knowledge, this is the first available data
      about the carriage rate of ESBL-PE in community infants in Lebanon and the Middle
      East, the first study showing that birth in hospital, caesarean delivery, and
      being formula-fed are all significantly associated risk factors for the high
      colonization rates in community - not hospitalized - infants, and showing the
      dominance of multiple resistance gene carriage and wide dissemination of CTX-M-9
      ESBL.

PMID- 27694728
TI  - Molecular diagnosis of infectious diseases in Sao Miguel Island (Azores,
      Portugal): A hospital-based descriptive study.
AB  - INTRODUCTION: We performed a descriptive analysis of molecular diagnosis of
      infectious agents in the Sao Miguel Island population, in order to address
      questions like what is the frequency of clinical requests, is it observable
      seasonality of pathogens, and what is the positive rate for the clinical
      diagnosis. METHODOLOGY: This was a retrospective and descriptive study based on
      878 individuals suspected of harboring infectious diseases during two consecutive
      years, 2012-2013. More than 25 different pathogens were investigated by
      polymerase chain reaction (PCR)-based methods. The individuals were stratified
      into gender, occupation, and age groups. RESULTS: The pathogen with more clinical
      requests was hepatitis C virus, investigated in 225 individuals (30.0%), followed
      by Leptospira spp., in 187 (24.9%). Overall, data demonstrated a gender
      distribution bias, where 72.9% of cases were males. The age group of 25 to 44
      years was the class with more clinical requests. Regarding occupation, a
      predominance of construction workers (12.0%) was observed, followed by retired
      workers (11.0%). Patient distribution per year showed a higher number of patients
      in the fall months. Diagnoses of leptospirosis and respiratory virus infections
      presented seasonality. CONCLUSIONS: The present study provides a valid
      contribution to the knowledge of the epidemiology of infectious diseases in the
      Sao Miguel Island (Azores, Portugal) population.

PMID- 27694730
TI  - The microRNA-let-7b-mediated attenuated strain of influenza A (H1N1) virus in a
      mouse model.
AB  - INTRODUCTION: Evaluating the attenuation of influenza viruses in animal studies
      is important in developing safe and effective vaccines. This study aimed to
      demonstrate that the microRNA (miRNA)-let-7b-mediated attenuated influenza
      viruses (miRT-H1N1) are sufficiently attenuated and safe in mice. METHODOLOGY:
      The pathogenicity of the miRT-H1N1virus was investigated in a mouse model,
      evaluated with median lethal dose (LD50). The replicative dynamics of the miRT
      H1N1, wild type (wt)-H1N1, and scramble (scbl)-H1N1 viruses in the lungs of
      infected mice were compared. The degrees of lesions and the expression levels of
      IL-6, TNF-alpha, and IFN-beta in the lungs of mice infected with different
      viruses were also analyzed. RESULTS: In miRT-H1N1 virus-infected mice, 100% of
      mice survived, and a lower pathogenicity was characterized with non-significant
      weight loss when compared to mice infected with the control wt virus. The miRT
      H1N1 virus was not fatal for mice, even at the highest dose administered. The
      viral load in the lungs of miRT-H1N1-infected mice was significantly lower than
      that of the wild-type virus-infected mice. Fewer pulmonary lesions and lower
      levels of selected pro-inflammatory cytokines in the lungs of the mice infected
      with the miRT-H1N1 virus were also observed. The virulence of the miRT-H1N1 virus
      reduced significantly, suggesting that the miRT-H1N1 virus was safe for mice.
      CONCLUSIONS: Our study demonstrated that the miRNA-mediated gene silencing is an
      alternative approach to attenuating the pathogenicity of wt influenza viruses
      that have potential in the development of influenza vaccines.

PMID- 27694729
TI  - HBV and HCV serological monitoring among injection drugs users in opiate
      substitution treatment in Bosnia and Herzegovina.
AB  - INTRODUCTION: Use of intravenous heroin carries a risk of serious medical
      conditions, including acquiring blood-borne infections. Therefore, hepatitis B
      virus (HBV) and hepatitis C virus (HCV) infection represent a threat for people
      who inject drugs (PWID). The objectives of this study were to determine the
      extent and characteristics of risk factors for acquiring HBV and HCV infection in
      PWID included in opiate substitution treatment in the southern part of Bosnia and
      Herzegovina (B&H). METHODOLOGY: The study included 120 adult PWID of both sexes
      who participated in opiate substitution treatment. All participants were
      interviewed, and their blood samples were tested for the presence of the surface
      hepatitis B virus antigen (HBsAg) and hepatitis C virus antibodies (anti-HCV).
      Prevalence data were obtained and compared to the serological status. RESULTS:
      HBsAg prevalence among PWID was 0.8% (1/120), whereas seroprevalence of anti-HCV
      was 52.5% (63/120). PWID exposed to risk-behavior factors (such as unsafe sexual
      activity, serving prison sentence, and tattooing) were more frequently anti-HCV
      positive. Sharing drug paraphernalia was found to be the most significant risk
      factor. The highest predictive values for acquiring HCV-infection were attributed
      to PWID who used heroin for more than three years and who were unmarried.
      CONCLUSIONS: HBsAg prevalence among PWID is rare (0.8%), while HCV-infection
      (52.5%) presents an important health and social issue among PWID in B&H. Sharing
      drug paraphernalia and intravenous heroin use longer than three years were the
      most prominent risk-behavior factors among the patients we investigated.

PMID- 27694731
TI  - Effectiveness of tipranavir versus darunavir as a salvage therapy in HIV-1
      treatment-experienced patients.
AB  - INTRODUCTION: Although both tipranavir (TPV) and darunavir (DRV) represent
      important options for the management of patients with multi-protease inhibitor
      (PI)-resistant human immunodeficiency virus (HIV), currently there are no studies
      comparing the effectiveness and safety of these two drugs in the Mexican
      population. The aim of this study was to compare the effectiveness of TPV versus
      DRV as a salvage therapy in HIV-1 treatment-experienced patients. METHODOLOGY:
      This was a comparative, prospective, cohort study. Patients with HIV and triple
      class drug resistance evaluated at the Hospital de Infectologia "La Raza",
      National Medical Center, were included. All patients had the protease and
      retrotranscriptase genotype; resistance mutation interpretation was done using
      the Stanford database. RESULTS: A total of 35 HIV-1 triple-class drug-resistant
      patients were analyzed. All of them received tenofovir and raltegravir, 22
      received darunavir/ritonavir (DRV/r), and 13 received tipranavir/ritonavir
      (TPV/r) therapies. The median baseline RNA HIV-1 viral load and CD4+ cell count
      were 4.34 log (interquartile range [IQR], 4.15-4.72) and 267 cells/mm3 (IQR, 177
      320) for the DRV/r group, and 4.14 log (IQR, 3.51-4.85) and 445 cells/mm3 (IQR,
      252-558) for the TPV/r group. At week 24 of treatment, 91% of patients receiving
      DRV/r and 100% of patients receiving TPV/r had an RNA HIV-1 viral load < 50
      copies/mL and a CD4+ cell count of 339 cells/mm3 (IQR, 252-447) and 556 cells/mm3
      (IQR, 364-659), respectively. CONCLUSIONS: No significant difference was observed
      between DRV/r and TPV/r in terms of virological suppression in HIV-1 patients who
      were highly experienced in antiretroviral therapy.

PMID- 27694732
TI  - Molecular genotyping of duck hepatitis A viruses (DHAV) in Vietnam.
AB  - INTRODUCTION: The aim of this study was to identify the genetic characteristics
      and molecular genotyping of duck hepatitis A virus (DHAV) isolated in Vietnam
      during 2009-2013. METHODOLOGY: Thirty duckling livers from outbreaks between 2009
      and 2013 in seven provinces were collected and identified by polymerase chain
      reaction (PCR). Then, VP1 genes of eleven positive samples and two attenuated
      vaccine strains were sequenced and analyzed. RESULTS: Genotypic and phylogenetic
      analyses indicated that the 13 Vietnamese isolates were classified into two
      genotypes, DHAV-1 and DHAV-3. The rate of identity and homology was 91%-100%
      between the 10 Vietnamese and 26 global strains of DHAV-3, and 92%-100% between 3
      Vietnamese and 16 strains of DHAV-1. Between the DHAV-3 and DHAV-1 strains, the
      divergence reached 30%. At the C-terminal of VP1 for the different strains, a
      hypervariable region was observed, and notably, six of the Vietnamese DHAV-3
      strains in this study showed four consistent differences (at positions T184M,
      Q200H, K207N, and K214R) within this group that were distinct from all other DHAV
      3 strains. CONCLUSIONS: This is the first report of molecular characterization of
      DHAVs in Vietnam. At least two genotypes were identified, DHAV-1 and DHAV-3, with
      diversified clades within and between genotypes. DHAV-3 seemed to be dominant in
      Vietnam.

PMID- 27694734
TI  - Public knowledge, perceptions, and attitudes towards HIV/AIDS in Bahrain: A cross
      sectional study.
AB  - INTRODUCTION: HIV/AIDS is one of the major health problems worldwide. Despite the
      low prevalence of HIV in Bahrain, educational and awareness programs remain
      highly important in controlling and preventing the spread of the disease. This
      study aimed to assess the public's knowledge, risk perceptions, and attitudes
      towards HIV/AIDS in Bahrain. METHODOLOGY: A self-administered questionnaire-based
      survey was administered to and completed by 1,038 Bahraini adults. RESULTS:
      Although the average general awareness among participants was good (63%), some
      misconceptions and erroneous beliefs were common, including knowledge of mode of
      transmission and high risk groups. Participants' attitudes towards HIV/AIDS
      patients varied but were mostly negative; 60% of respondents agreed to isolating
      HIV/AIDS patients in workplaces and schools, and 52.4% of them thought that HIV
      is a divine punishment. The vast majority of the participants (84.4%) believed in
      the role of religion in limiting the spread of the disease. Though the local
      media was the least utilized source of information, the general opinion of the
      participants about the role of Bahraini government agencies and organizations in
      combating HIV/AIDS was positive. CONCLUSIONS: Though the Bahraini public had good
      knowledge about HIV/AIDS, there were misconceptions that need to be addressed. A
      major finding of this study was the negative attitudes towards HIV/AIDS patients.
      To have successful HIV control programs, negative attitudes towards HIV patients
      and the disease should be minimized. Existing and newly proposed health education
      and awareness program in Bahrain should address the issue of negative attitudes
      towards HIV/AIDS observed in this study.

PMID- 27694733
TI  - Monitoring of genotypic resistance profile in chronic hepatitis B patients
      receiving nucleos(t)ide analogues in Huzhou, China.
AB  - INTRODUCTION: Antiviral drug-resistance patterns of hepatitis B virus (HBV)
      mutants are complex and currently partly understood. The aim of this study was to
      monitor the genotypic resistance profile in patients with chronic hepatitis B
      (CHB) receiving nucleos(t)ide analogues (NAs) in Huzhou, eastern China.
      METHODOLOGY: Serum samples of 139 CHB patients undergoing NA treatment were
      obtained from Huzhou Central Hospital. The full-length HBV reverse transcriptase
      regions were amplified and sequenced. The NA resistance mutation positions,
      including rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204,
      rtI233, rtN236, and rtM250 were analyzed. RESULTS: Genotypic resistance mutations
      were detected in 41.72% (58/139) of patients with CHB. Drug resistance mutations
      were detected at positions rt80, rt173, rt180, rt181, rt194, rt202, rt204, rt236,
      and rt250, but were not observed at positions rt169, rt184, and rt233. The
      prevalence of mutations at rtM204 was 54.44% in 90 patients who were treated with
      lamivudine (LAM) or telbivudine (LDT). RtN236 mutations were detected in 7.14%
      (2/28) of the patients receiving adefovir (ADV) therapy. Additionally, rtA181
      mutations were observed in 4 patients with LAM, ADV, and LDT-based therapy, but
      not in those patients treated with entecavir (ETV). Among patients who harbored
      rtM204 combination mutations, rtM204I and rtM204V were significantly associated
      with rtL80I/V and rtL180M, respectively. CONCLUSIONS: The mutation patterns of NA
      resistant HBV are complicated in CHB patients in the current clinical setting.
      Thus, it is necessary to persistently monitor the resistance mutations of HBV for
      optimizing antiviral therapy strategy and for preventing an outbreak of clinical
      resistance.

PMID- 27694735
TI  - Intestinal parasitic infections and associated epidemiological drivers in two
      rural communities of the Bolivian Chaco.
AB  - INTRODUCTION: In 2013 a coproparasitological survey was carried out in two rural
      communities of the Bolivian Chaco to determine the prevalence of intestinal
      parasitic infections (IPIs) and to investigate on possible infection drivers
      through a questionnaire interview. METHODOLOGY: Faecal samples were examined by
      microscopy. Samples positive for Entamoeba histolytica complex and Blastocystis
      were molecularly examined to identify the species/subtypes involved. RESULTS: The
      overall infection rate was 86%, identical in both communities and mostly due to
      protozoa. Soil-transmitted helminths were detected in <3% of children and adults.
      DISCUSSION: The protozoa detected, including Blastocystis subtypes, indicate
      faecal contamination of the environment by both humans (as confirmed by the
      presence of Hymenolepis nana) and animals. Nested-PCR identified E. histolytica,
      thus signalling the possible occurrence of invasive amoebosis. Lack of safe
      water, environmental contamination, poor sanitation and hygiene, shared by both
      communities, are the main drivers of IPIs. In addition, unlike gender and
      socioeconomic factors, childhood (only for some species), crowding and
      cohabitation with animals proved to be further significant protozoon infection
      risk factors. CONCLUSIONS: These results highlight the need for the promotion of
      access to clean water, improved sanitation and better hygiene, thus reducing the
      frequency of preventive chemotherapy for STHs while continuing to monitor the
      population for possible recrudescence.

PMID- 27694736
TI  - Anti-proteolytic activity of Ganoderma lucidum methanol extract against
      Pseudomonas aeruginosa.
AB  - INTRODUCTION: Protease enzyme is considered one of the most serious virulence
      factors produced by extended-spectrum beta-lactamase-producing and multidrug
      resistant Pseudomonas aeruginosa (ESbetaLMDRPA) clinical isolates. METHODOLOGY:
      The antibacterial activity of methanol extract of Ganoderma lucidum fruiting
      bodies was tested against a protease-producing ESbetaLMDRPA clinical isolate,
      showing its mode of action. RESULTS: The extract showed high antibacterial
      activity. Its effect on purified protease indicated a reversible non-competitive
      protease inhibition (kis= 0.45 mg/mL). CONCLUSIONS: The G. lucidum extract could
      be a promising anti-proteolytic active against ESbetaLMDRPA. It may form a
      primary platform for further phytochemical studies and development of new drugs
      for therapy of skin burn infections.

PMID- 27694737
TI  - Relationships between low serum vitamin D levels and HBV "a" determinant
      mutations in chronic hepatitis B patients.
AB  - INTRODUCTION: Vitamin D is significantly associated with virus replication in
      chronic hepatitis B virus (HBV) infection. However, the relationship between low
      serum vitamin D levels and HBV "a" determinant mutations remains unknown.
      METHODOLOGY: A total of 133 chronically HBV-infected, treatment-naive patients
      were randomly selected in the present study. Serum vitamin D levels were measured
      by using liquid chromatography-mass spectrometry. The HBV "a" determinant was
      amplified, sequenced, and analyzed by nested polymerase chain reaction (PCR).
      RESULTS: Among 133 patients, 36, 88, and 9 patients had vitamin D deficiency
      (25(OH)D < 14 ng/mL), vitamin D insufficiency (25(OH)D >= 14 and < 30 ng/mL), and
      normal vitamin D serum levels ((25(OH)D >= 30 ng/mL), respectively. As results
      showed, 36 [11 genotype B HBVs (HBV/B) and 25 genotype C HBVs (HBV/C)] were
      isolated from the vitamin D-deficient group, 88 (48 HBV/B and 40 HBV/C) from the
      vitamin D-insufficient group, and 4 HBV/C strains from the normal serum-vitamin D
      group. Compared to the HBV/B infected patients with vitamin D insufficiency,
      higher rates of amino acid mutation within "a" determinant were detected in HBV/B
      infected, vitamin D-deficient patients. Moreover, the change frequency of M133
      was 27.27% in HBV/B infected patients with vitamin D deficiency, which was
      significantly higher than those in the vitamin D-insufficient group (p = 0.040).
      CONCLUSIONS: Vitamin D deficiency is significantly associated with genotype B HBV
      "a" determinant mutations.

PMID- 27694738
TI  - Reflex threshold of signal-to-cut-off ratios of the Elecsys anti-HCV II assay for
      hepatitis C virus infection.
AB  - INTRODUCTION: Fast screening tests for hepatitis C virus (HCV) antibody often
      give false-positive results. Signal-to-cut-off (S/Co) ratios were suggested to be
      used as reflex confirmation of anti-HCV. The Elecsys Anti-HCV II assay is an
      effective test for the detection of hepatitis C, but no S/Co cutoff has been
      reported. The aim of this study was to determine the S/Co ratio threshold of anti
      HCV test using Elecsys Anti-HCV II screening and supplemental recombinant
      immunoblot assay (RIBA) test results as the gold standard. METHODOLOGY: A total
      of 36,341 serum samples were tested for HCV antibody using the Elecsys Anti-HCV
      II assay and 276 positive samples were then tested with supplemental RIBA
      (Mikrogen recomLine HCV IgG strip immunoassay). Receiver operation curve (ROC)
      analysis was used to determine the cutoff, sensitivity, and specificity of the
      optimal S/Co ratio. RESULTS: The Elecsys Anti-HCV II assay was positive (S/Co
      ratio >= 1) in 288 of the 36,341 samples (0.79%). RIBA testing on 276 of these
      288 positive samples showed that all but one of 44 samples with an S/Co ratio of
      >= 1 and < 10 were negative, whereas the vast majority of samples (223/232,
      96.1%) with an S/Co ratio >= 10 were positive. ROC analysis revealed that an
      optimal S/Co ratio cut-off value was 12.27. CONCLUSIONS: An S/Co ratio of 12.27
      obtained with the Elecsys Anti-HCV II assay could be used as reflex confirmation
      of anti-HCV tests.

PMID- 27694739
TI  - Gut microbiota related to Giardia duodenalis, Entamoeba spp. and Blastocystis
      hominis infections in humans from Cote d'Ivoire.
AB  - INTRODUCTION: Literature data provide little information about protozoa
      infections and gut microbiota compositional shifts in humans. This preliminary
      study aimed to describe the fecal bacterial community composition of people from
      Cote d'Ivoire harboring Giardia duodenalis, Entamoeba spp., and Blastocystis
      hominis, in trying to discover possible alterations in their fecal microbiota
      structure related to the presence of such parasites. METHODOLOGY: Twenty fecal
      samples were collected from people inhabiting three different localities of Cote
      d'Ivoire for copromicroscopic analysis and molecular identification of G.
      duodenalis, Entamoeba spp., and B. hominis. Temporal temperature gradient gel
      electrophoresis (TTGE) was used to obtain a fingerprint of the overall bacterial
      community; quantitative polymerase chain reaction (qPCR) was used to define the
      relative abundances of selected bacterial species/group, and multivariate
      statistical analyses were employed to correlate all data. RESULTS: Cluster
      analysis revealed a significant separation of TTGE profiles into four clusters (p
      < 0.0001), with a marked difference for G. duodenalis-positive samples in
      relation to the others (p = 5.4*10-6). Interestingly, qPCR data showed how G.
      duodenalis-positive samples were related to a dysbiotic condition that favors
      potentially harmful species (such as Escherichia coli), while Entamoeba spp./B.
      hominis-positive subjects were linked to a eubiotic condition, as shown by a
      significantly higher Faecalibacterium prausnitzii-Escherichia coli ratio.
      CONCLUSIONS: This preliminary investigation demonstrates a differential fecal
      microbiota structure in subjects infected with G. duodenalis or Entamoeba spp./B.
      hominis, paving the way for using further next-generation DNA technologies to
      better understand host-parasite-bacteria interactions, aimed at identifying
      potential indicators of microbiota changes.

PMID- 27694740
TI  - First HIV-2 infection in a child in Turkey.

PMID- 27694742
TI  - WNT signaling determines tumorigenicity and function of ESC-derived retinal
      progenitors.

PMID- 27694743
TI  - Teri Lear, PhD (1951-2016).

PMID- 27694745
TI  - Emergence of Dipstick Proteinuria Predicts Overt Nephropathy in Patients
      Following Stem Cell Transplantation.
AB  - BACKGROUND: Stem cell transplantation (SCT) places a heavy burden on the kidneys,
      often resulting in renal dysfunction or nephrotic syndrome. This study attempted
      to show that early-onset proteinuria predicts the development of overt
      nephropathy. METHODS: A total of 831 patients who received allogeneic SCT were
      surveyed. Excluding those with prior kidney disease and those lacking in an
      observation period >=1 year after SCT, 251 patients were eligible for the study.
      Dipstick proteinuria >=1+ within 1 year after SCT was defined as 'incident
      proteinuria', and subsequent persistence of an estimated glomerular filtration
      rate of <60 ml/min/1.73 m2 at 1 year or longer after SCT was defined as 'incident
      chronic kidney disease (CKD)'. Between-group differences were analyzed using the
      chi-square or Mann-Whitney U test. Factors associated with the incidence of CKD
      were investigated by multivariate Cox proportional regression analysis. Kidney
      biopsied tissue was examined in all nephrotic syndrome patients. RESULTS: The
      mean duration of follow-up was 4 years. Thirty-four (13.5%) and 66 (26.3%)
      patients developed incident proteinuria and incident CKD, respectively. Nine
      (3.6%) patients developed nephrotic syndrome mainly due to membranous
      nephropathy. The incidence of CKD was significantly greater in patients with
      incident proteinuria than those without (61.8 vs. 20.7%, p < 0.0001), and
      incident dipstick proteinuria was a significant risk for incident CKD (hazard
      ratio 4.39, 95% CI 2.44-7.73, p < 0.0001). CONCLUSION: SCT patients who manifest
      dipstick proteinuria are predisposed to overt nephropathy. Routine monitoring of
      the urine dipstick test is strongly recommended, as it facilitates early
      nephrology care for post-SCT patients.

PMID- 27694744
TI  - The Impact of Obesity on Outcomes Following Resection for Gastric Cancer.
AB  - BACKGROUND: Obesity is generally considered to be associated with increased
      postoperative morbidity and mortality following intraabdominal cancer surgery.
      However, recent reports showed that overweight patients may have a lower risk for
      adverse postoperative outcomes and this observation has been described as the
      'obesity paradox'. Therefore, we aimed to analyze the impact of obesity on
      outcomes after resection for gastric cancer. METHODS: Data of patients who
      underwent resection for gastric cancer between 2005 and 2012 were assessed.
      Patient characteristics, postoperative outcomes and long-term survivals were
      compared between patients with body mass index (BMI) >=30 and <30. RESULTS:
      Resection for gastric cancer was performed in 249 patients. BMI >=30 was
      identified in 49 patients. Obese patients with BMI >=30 were more frequently
      diagnosed with diabetes (31 vs. 16%, p = 0.015). Resection for gastric cancer in
      obese patients was significantly associated with longer duration of surgery (278
      vs. 243 min, p < 0.001), longer duration of hospital stay (18 vs. 16 days, p =
      0.028), increased postoperative morbidity (49 vs. 33%, p = 0.037), and increased
      postoperative mortality (10 vs. 3%, p = 0.028). There was no significant
      difference in overall survival (OS) between patients with BMI >=30 and patients
      with BMI <30 (5-year OS rate: 59 vs. 62%, p = 0.587). CONCLUSION: Obesity may
      complicate resection for gastric cancer increasing the duration of surgical
      procedure, hospital stay and postoperative morbidity and mortality. However, BMI
      did not predict OS in our patients. Consequently, BMI may be too simple as a
      parameter to evaluate sophisticated interactions between different body fat
      compartments and inflammatory and immune responses and thus to predict long-term
      oncologic outcomes.

PMID- 27694746
TI  - Molecular Epidemiology of Human Metapneumovirus in Riyadh Province, Saudi Arabia.
AB  - Human metapneumovirus (HMPV) is an important cause of respiratory tract illness
      in children. Two HMPV subgroups, A and B, and four genotypes, A1, A2, B1 and B2,
      have been identified. Concurrent circulation of the different genotypes in yearly
      epidemics has been recorded globally, but not in Saudi Arabia. The current report
      was designed to study HMPV epidemiology in Saudi children and to analyze the
      genetic diversity and circulation patterns. Nasopharyngeal aspirates (n = 174)
      were collected from hospitalized children in Riyadh (2008-2009). The screening of
      samples using real-time RT-PCR identified 19 HMPV strains. The majority of the
      strains belonged to subgroup B, while all strains of subgroup A were members of
      genotype A2. In 2008, only subgroup B was recognized, whereas in 2009 both
      subgroups were identified to be cocirculating at similar rates. The full-length
      attachment (G) gene and a partial sequence of the fusion (F) gene of positive
      samples were sequenced. The G gene showed a high degree of genetic diversity and
      exhibited a variable number of positively selected sites in different lineages.
      In contrast, the F gene demonstrated an extensive genetic stability with a higher
      tendency toward purifying selection. This is the first report on HMPV genotype
      circulation in Saudi Arabia; however, the exact circulation kinetics requires
      further retrospective and prospective study.

PMID- 27694747
TI  - Language Development of Three- to Twelve-Year-Old Twins Compared to Singletons.
AB  - OBJECTIVE: The language development of twins tends to lag behind in comparison to
      that of singletons. The purpose of this study was to compare expressive and
      receptive language skills of 3- to 12-year-old twins with singletons. Secondly,
      correlations between language differences between twins and singletons and age
      were investigated. PATIENTS AND METHODS: Twenty-four twins with a mean age of 5.1
      years participated in the study. The control group consisted of 24 singletons who
      were matched for gender and age. Language development was investigated using the
      Clinical Evaluation of Language Fundamentals. RESULTS: Twins scored significantly
      lower for expressive and receptive language skills compared to singletons. Even
      when excluding preterm-born children, twins still scored significantly lower for
      expressive language skills. There was no correlation between age and language
      differences between twins and their matched singletons. CONCLUSION: Twins score
      lower for expressive and receptive language skills compared to singletons, and
      preterm birth cannot be regarded as the main cause for the language delay. The
      language delay in twins is rather mild but does not seem to decrease with
      increasing age.

PMID- 27694748
TI  - Impact of Rectal Swabs on Infectious Complications after Transrectal Prostate
      Biopsy.
AB  - OBJECTIVES: To determine the impact of rectal swabs (RSs) on infectious
      complications (IC) following prostate biopsy (PB). METHODS: A retrospective
      cohort study was conducted including all patients subjected to PB between 2009
      and 2013. Group B consisted of patients with a RS and group A of patients
      without. RS reported the presence of gram-positive or negative germs, sensitive
      or resistant to ciprofloxacin. Antimicrobial prophylaxis was adjusted to the
      result. Frequency of IC in each group was determined. RESULTS: Group B had 548
      (47.20%) patients and group A 613 (52.80%). From group B, 250 (45.62%) of the RSs
      showed fluoroquinolone (FQ)-resistant germs. Forty nine (16.44%) patients with
      sensitive germs vs. 147 (59.51%) with resistant germs had a history of previous
      FQ treatment (p < 0.0001). IC were observed in 33 (5.49%) patients from group A
      and in 7 (1.28%) patients from group B (p < 0.0001), requiring hospitalization in
      4.99 vs. 1.28%, respectively. IC and hospital admissions were reduced in 76.68
      and 74.34%, respectively, following the implementation of RS. CONCLUSIONS: RS and
      targeted antibiotic prophylaxis prior to PB was associated with a significant
      reduction in IC and hospital admissions. Ceftriaxone could be an alternative in
      cases of known resistance. Past history of FQ treatment is associated with
      increased resistance.

PMID- 27694741
TI  - Advances in beta cell replacement and regeneration strategies for treating
      diabetes.
AB  - In the past decade, new approaches have been explored that are aimed at restoring
      functional beta cell mass as a treatment strategy for diabetes. The two most
      intensely pursued strategies are beta cell replacement through conversion of
      other cell types and beta cell regeneration by enhancement of beta cell
      replication. The approach closest to clinical implementation is the replacement
      of beta cells with human pluripotent stem cell-derived (hPSC-derived) cells,
      which are currently under investigation in a clinical trial to assess their
      safety in humans. In addition, there has been success in reprogramming
      developmentally related cell types into beta cells. Reprogramming approaches
      could find therapeutic applications by inducing beta cell conversion in vivo or
      by reprogramming cells ex vivo followed by implantation. Finally, recent studies
      have revealed novel pharmacologic targets for stimulating beta cell replication.
      Manipulating these targets or the pathways they regulate could be a strategy for
      promoting the expansion of residual beta cells in diabetic patients. Here, we
      provide an overview of progress made toward beta cell replacement and
      regeneration and discuss promises and challenges for clinical implementation of
      these strategies.

PMID- 27694749
TI  - Effects of Liraglutide and Vitamin E in Fructose-Induced Metabolic Syndrome in
      Rats.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a growing worldwide health problem.
      However, there is yet no effective therapy for MetS. The present work
      investigated the effect of liraglutide, a synthetic glucagon-like peptide-1 and
      vitamin E on fructose-induced MetS in rats. SUMMARY: Liraglutide (0.3 mg/kg/day)
      and vitamin E (100 mg/kg/day) were administered either alone or in combination
      with high fructose-fed male rats for 6 weeks. Fructose-fed rats developed
      metabolic disorders assessed by visceral fat index, serum glucose, serum insulin,
      homeostasis model assessment-insulin resistance and serum lipids profile and
      hepatic disorders assessed by liver index, serum alanine aminotransferase and
      aspartate aminotransferase and steatohepatitis in histopathology. This study
      showed that liraglutide, vitamin E and their combination significantly
      ameliorated the fructose-induced metabolic and hepatic disorders. Key Messages:
      These results indicate a potential therapeutic benefit of liraglutide and vitamin
      E combination in prevention of MetS. Their protective effects might rely on their
      antioxidant effects as well as on the inhibition of tumor necrosis factor-alpha.

PMID- 27694750
TI  - Exposure of Piglets to Enteroviruses Investigated by an Immunoassay Based on the
      EV-G1 VP4 Peptide.
AB  - OBJECTIVE: The aim of this study was to investigate the exposure of piglets to
      enteroviruses-G (EV-G) through the presence of antibodies in their serum.
      METHODS: Serum samples were obtained from the vena cava of 10 piglets at 9 weeks
      of age and again 39 days later (day 39). They were tested using an immunoassay
      based on the EV-G1 VP4 peptide, since VP4 is highly conserved among the four
      Enterovirus capsid proteins, and by using a seroneutralization assay. RESULTS:
      For each serum collected on day 39 the optical density was high compared to the
      value obtained in serum collected earlier (p = 0.002). However, the titers of
      anti-EV-G1 serum neutralizing activity were not different in paired samples (p >
      0.999). The sequence alignment of the EV-G1 VP4 peptide, encompassing 50 amino
      acids, used in the immunoassay showed 88% homology with EV-G, suggesting that
      antibodies directed toward other EV-G than EV-G1 may be detected. CONCLUSION: An
      immunoassay based on EV-G1 VP4 can detect an increased level of EV-G antibodies
      in piglet serum samples. Further studies are needed to determine whether this
      immunoassay may be useful for diagnosis and/or epidemiological studies and to
      monitor EV-G infection in pigs to evaluate strategies aimed to prevent
      enterovirus infections.

PMID- 27694751
TI  - Non-Responders to Intravitreal Ranibizumab in Subfoveal Choroidal
      Neovascularization Secondary to Age-Related Macular Degeneration.
AB  - AIM: Evaluation of the proportion of patients affected by subfoveal choroidal
      neovascularization secondary to age-related macular degeneration who are non
      respondent to intravitreal ranibizumab injections (IVRI). METHODS: Patients
      received 3 monthly IVRI, with monthly retreatments, in accordance with a pro re
      nata scheme (fluid on optical coherence tomography, leakage on fluorescein
      angiography, new haemorrhages). Non-responders were classified as follows:
      functional non-responder (best-corrected visual acuity worsening by a minimum of
      2 ETDRS lines); anatomical non-responder (central foveal thickness not decreasing
      by at least 10% compared with baseline value); complete non-responder (both
      anatomical and functional non-responder criteria apply). PRIMARY OUTCOME MEASURE:
      identification of the proportion of non-responders. RESULTS: Four patients (7%)
      were functional non-responders at the 1-month examination, and 5, 5 and 7% at the
      2-, 3- and 6-month examinations, respectively. Two of 4 initial non-responders
      were reclassified as responders during the 6-month follow-up. Twenty-three eyes
      (43%) were anatomical non-responders at the 1-month visit, and 32, 28 and 21% at
      2, 3 and 6 months, respectively. Sixteen of 23 (70%) initially non-respondent
      eyes became respondent over the follow-up. Two eyes (4%) were classified as
      complete non-responders after 1 month. Non-responders amounted to 4, 0 and 2% at
      the 2-, 3- and 6-month examinations, respectively. No initially complete non
      responding eye remained so over the follow-up. CONCLUSION: Data indicate a low
      proportion of functional and anatomical non-responders to IVRI. Further studies
      are warranted providing a better definition of non-responder and a clearer
      picture of the magnitude of response, when present.

PMID- 27694752
TI  - Nerve Growth Factor Facilitates the Innervation of Perivascular Nerves in Tumor
      Derived Neovasculature in the Mouse Cornea.
AB  - BACKGROUND: Tumor neovascular vessels are not innervated by perivascular nerves.
      This study was an investigation of the effects of the nerve growth factor (NGF)
      on the distribution of perivascular nerves and neovessel formation in tumor
      tissues. METHODS: A gel containing DU145 prostate carcinoma cells or HT1080
      fibrosarcoma cells was implanted into mouse corneas. NGF was subcutaneously
      administered using an osmotic mini-pump. The distribution of perivascular nerves
      in mouse corneas and densities of CD31-immunopositive neovessels and smooth
      muscles (alpha-smooth muscle actin, alpha-SMA) in tumor tissues were quantified.
      SUMMARY: Neovessels generated from corneal limber arteries in tumor tissues were
      observed 4-14 days after the implantation of tumor cells. The density of CD31
      immunopositive cells in endothelium increased after the implantation of DU145 or
      HT1080 cells, while that of alpha-SMA-immunopositive cells slightly increased.
      The NGF treatment significantly increased the density of alpha-SMA- but not that
      of CD31-immunopositive cells (except for DU145 cells) and resulted in the
      innervation of perivascular nerves around tumor-derived neovessels, whereas no
      innervation was observed in the control group. Key Messages: These results
      suggest that NGF facilitates the innervation of perivascular nerves to regulate
      blood flow into tumor-derived neovessels.

PMID- 27694753
TI  - The Influence of Hemodialysis on T Regulatory Cells: A Meta-Analysis and
      Systematic Review.
AB  - AIMS: The study aimed to determine whether the available literature supports a
      positive or negative influence of dialysis on regulatory T-cells (Tregs).
      METHODS: We performed a systematic search and a meta-analysis. Mean differences
      in Tregs number of chronic kidney disease stages G5 on dialysis patients (CKD
      G5D) and healthy controls (HCs) were compared. Random effects model was applied.
      The software used was general package for meta-analysis (version 4.3-0, depends R
      (>=2.9.1)). RESULTS: Five studies were included in the meta-analysis. The mean
      difference in percentage of Tregs on CD4+ T-cells between CKD G5D and HCs was not
      statistically different. Moreover, CKD GFR stages G5 not on dialysis (CKD G5)
      versus HC (p = 0.002; mean difference in Treg percentage was -2.47% in CKD G5 vs.
      HC) and CKD G5 versus CKD G5D (not significant). CONCLUSION: This meta-analysis
      demonstrates an association between the uremic state and lower Tregs, and
      supports the hypothesis that hemodialysis alter Tregs. Our findings highlight the
      need for new clinical studies. Video Journal Club 'Cappuccino with Claudio Ronco'
      at http://www.karger.com/?doi=449242.

PMID- 27694754
TI  - Liver Fibrosis and Body Mass Index Predict Hepatocarcinogenesis following
      Eradication of Hepatitis C Virus RNA by Direct-Acting Antivirals.
AB  - BACKGROUND AND AIMS: Predictive factors for hepatocarcinogenesis following
      eradication of hepatitis C virus (HCV) RNA by antiviral therapy with direct
      acting antivirals are unknown. Especially the impact of treatment with or without
      interferon on hepatocarcinogenesis is not clear. METHODS: A total of 958 patients
      with HCV genotype 1-related chronic liver disease and a sustained virological
      response defined as negative HCV RNA 24 weeks after cessation of antiviral
      therapy with direct-acting antivirals (triple therapy of NS3/4A protease
      inhibitor/peginterferon/ribavirin or all-oral combination therapy with NS3/4A
      protease inhibitor plus NS5A inhibitor) were included in a retrospective study.
      None of the patients had hepatocellular carcinoma before and during antiviral
      therapy. RESULTS: In all, 14 patients developed hepatocellular carcinoma during
      follow-up, and the development rate per 1,000 person-years was 7.35. The
      cumulative hepatocarcinogenesis rates were 4.2 and 4.2% at the end of 5 and 7
      years, respectively. Multivariate analysis identified fibrosis 4 (FIB4) index
      (>=2.7) and body mass index (>=23.0) as determinants of hepatocarcinogenesis, but
      they did not identify the treatment regimen. In patients with a FIB4 index >=2.7,
      the hepatocarcinogenesis rates with the interferon regimen were not different
      from those for the regimen without interferon, regardless of gender. CONCLUSION:
      Liver fibrosis and body mass index, but not treatment regimen, are important
      predictors of hepatocarcinogenesis following eradication of HCV RNA by direct
      acting antivirals.

PMID- 27694755
TI  - Assessment of Uric Acid Level in the Saliva of Patients with Oral Lichen Planus.
AB  - OBJECTIVE: The aim of this study was to evaluate the level of uric acid (UA) in
      saliva, which is considered to be an antioxidant defense biomarker against
      oxidative stress in patients with oral lichen planus (OLP). SUBJECTS AND METHODS:
      In this case-control study, 25 OLP patients were included. The reticular form of
      OLP was verified by a clinical examination with Wickham striae, and other types
      (erosive, atrophic, ulcerative) were confirmed by histopathological assessment.
      Thirty healthy individuals matched for age and gender were selected as the
      control group. In both groups, the Navazesh technique was used to collect the
      unstimulated saliva. Then, the amount of UA was measured using a Cobas Mira
      autoanalyzer with a wavelength of 546 nm. The Student t test was used to analyze
      the data assuming a significance level at <0.05. RESULTS: Of the 25 patients, the
      most common type of OLP was erosive (n = 11, 44%), and the most common site of
      OLP was seen as bilateral in the buccal mucosa (n = 12, 48%). The mean level of
      salivary UA was significantly lower in the patients with OLP (2.10 +/- 0.19
      mg/dL) in comparison with the control group (4.80 +/- 0.29 mg/dL; p < 0.001).
      CONCLUSION: In this study, OLP was associated with a decrease in UA levels in the
      saliva. Salivary UA as a biomarker could be used for monitoring and treating OLP.

PMID- 27694756
TI  - Exploring the Relationship between Sexual Compulsivity and Attentional Bias to
      Sex-Related Words in a Cohort of Sexually Active Individuals.
AB  - BACKGROUND/AIMS: If sexual compulsivity and other addictive behaviours share
      common aetiology, contemporary proposals about the role of attentional processes
      in understanding addictive behaviours are relevant. METHODS: To examine
      attentional biases for sex-related words among sexually active individuals and
      the relationship between sexual compulsivity and sexual behavioural engagement
      with attentional bias, 55 sexually active individuals completed a modified Stroop
      task and the sexual compulsivity scale. RESULTS: Findings showed attentional bias
      towards sex-related stimuli among sexually active participants. In addition,
      among those with low levels of sexual compulsivity, levels of attentional bias
      were the same across all levels of sexual experience. Among those with higher
      levels of sexual compulsivity, greater attentional bias was linked with lower
      levels of sexual experience. CONCLUSION: Attentional preference for concern
      related stimuli varies as a function of the interaction between how long a person
      has been active sexually and how compulsive their sexual behaviour is.

PMID- 27694757
TI  - The Prevalence of Tooth Wear in the Dutch Adult Population.
AB  - This study aimed to assess the prevalence of tooth wear in different age groups
      of the Dutch adult population and to determine this tooth wear distribution by
      gender, socioeconomic class, and type of teeth. Results were compared with the
      outcomes of a previous study in a comparable population. As part of a
      comprehensive investigation of the oral health of the general Dutch adult
      population in 2013, tooth wear was assessed among 1,125 subjects in the city of
      's-Hertogenbosch. The data collected were subjected to stratified analysis by 5
      age groups (25-34, 35-44, 45-54, 55-64, and 65-74 years), gender, socioeconomic
      class, and type of teeth. Tooth wear was assessed using a 5-point ordinal
      occlusal/incisal grading scale. The number of teeth affected was higher in older
      age groups. Men showed more tooth wear than women, and subjects with low
      socioeconomic status (low SES) showed on average higher scores than those with
      high SES. Tooth wear prevalence found in this study was higher in all age groups
      than in the previous study. The present study found prevalences of 13% for mild
      tooth wear and 80% for moderate tooth wear, leading to the conclusion that these
      are common conditions in the Dutch adult population. Severe tooth wear
      (prevalence 6%) may however be characterized as rare. A tendency was found for
      there to be more tooth wear in older age groups, in men as compared with women,
      in persons with lower SES, and in the present survey as compared with the
      previous one.

PMID- 27694759
TI  - Trends in Upper Tract Stone Disease in England: Evidence from the Hospital
      Episodes Statistics Database.
AB  - AIMS: The study aimed to determine the current trends in urolithiasis-related
      admissions and associated interventions in England between 2006/2007 and
      2013/2014 utilizing Hospital Episode Statistics (HES) online data. MATERIAL AND
      METHODS: Data was extracted from the online HES data set for each year from
      2006/2007 to 2013/2014 inclusive. Admissions and procedural interventions were
      identified from their corresponding OPCS-4 and ICD-10 codes. RESULTS: Finished
      consultant episodes (FCEs) for urolithiasis have increased by 20% over the last 7
      years, with 93,039 FCEs in the year 2013/2014. Based on English population
      statistics, the lifetime prevalence of urolithiasis based on hospital-related
      admission/intervention data for 2013/2014 is 14%. The biggest increases were seen
      in those aged >=75 years (up by 51%, n = 2,853). Total interventions have
      increased from 28,624 to 42,068, with increased rates of shock wave lithotripsy
      (26%), ureteroscopy (URS; 86%) and percutaneous nephrolithotomy (149%). Emergency
      URS procedures have increased by 38%. Day-case rates for ureteric and renal URS,
      in 2013/2014, were 22 and 21%, respectively. CONCLUSIONS: Over the last 7 years,
      there is a rising prevalence of kidney stone disease with associated increase in
      the number of interventions related to it. Both elective and emergency URS
      procedures are increasing, with a rising trend for day-case URS. Similar trends
      are seen worldwide and future resource planning for urolithiasis is needed to
      match the increase in demand.

PMID- 27694760
TI  - Microorganisms-A Forum for Understanding Microbial Life in All Its Forms.
AB  - It is my great pleasure to welcome you to Microorganisms, a new open access
      journal, which is dedicated to microorganisms in all their forms and via any
      approach to their study. [...].

PMID- 27694758
TI  - Study of hTERT and Histone 3 Mutations in Medulloblastoma.
AB  - Hotspot activating mutations of the telomerase reverse transcriptase (hTERT)
      promoter region were recently described in several tumor types. These mutations
      lead to enhanced expression of telomerase, being responsible for telomere
      maintenance and allowing continuous cell division. Additionally, there are
      alternative telomere maintenance mechanisms, associated with histone H3
      mutations, responsible for disrupting the histone code and affecting the
      regulation of transcription. Here, we investigated the clinical relevance of
      these mechanistically related molecules in medulloblastoma. Sixty-nine
      medulloblastomas, formalin fixed and paraffin embedded, from a cohort of patients
      aged 1.5-70 years, were used to investigate the hotspot mutations of the hTERT
      promoter region, i.e. H3F3A and HIST1H3B, using Sanger sequencing. We
      successfully sequenced hTERT in all 69 medulloblastoma samples and identified a
      total of 19 mutated cases (27.5%). c.-124:G>A and c.-146:G>A mutations were
      detected, respectively, in 16 and 3 samples. Similar to previous reports, hTERT
      mutations were more frequent in older patients (p < 0.0001), being found only in
      5 patients <20 years of age. In addition, hTERT-mutated tumors were more
      frequently recurrent (p = 0.026) and hTERT mutations were significantly enriched
      in tumors located in the right cerebellar hemisphere (p = 0.039). No mutations
      were found on the H3F3A or HIST1H3B genes. hTERT promoter mutations are frequent
      in medulloblastoma and are associated with older patients, prone to recurrence
      and located in the right cerebellar hemisphere. On the other hand, histone 3
      mutations do not seem to be present in medulloblastoma.

PMID- 27694761
TI  - Understanding Bioluminescence in Dinoflagellates-How Far Have We Come?
AB  - Some dinoflagellates possess the remarkable genetic, biochemical, and cellular
      machinery to produce bioluminescence. Bioluminescent species appear to be
      ubiquitous in surface waters globally and include numerous cosmopolitan and
      harmful taxa. Nevertheless, bioluminescence remains an enigmatic topic in
      biology, particularly with regard to the organisms' lifestyle. In this paper, we
      review the literature on the cellular mechanisms, molecular evolution, diversity,
      and ecology of bioluminescence in dinoflagellates, highlighting significant
      discoveries of the last quarter of a century. We identify significant gaps in our
      knowledge and conflicting information and propose some important research
      questions that need to be addressed to advance this research field.

PMID- 27694762
TI  - Circadian Rhythms in Dinoflagellates: What Is the Purpose of Synthesis and
      Destruction of Proteins?
AB  - There is a prominent circadian rhythm of bioluminescence in many species of light
      emitting dinoflagellates. In Lingulodinium polyedrum a daily synthesis and
      destruction of proteins is used to regulate activity. Experiments indicate that
      the amino acids from the degradation are conserved and incorporated into the
      resynthesized protein in the subsequent cycle. A different species, Pyrocystis
      lunula, also exhibits a rhythm of bioluminescence, but the luciferase is not
      destroyed and resynthesized each cycle. This paper posits that synthesis and
      destruction constitutes a cellular mechanism to conserve nitrogen in an
      environment where the resource is limiting.

PMID- 27694764
TI  - The Genus Neoceratium (Planktonic Dinoflagellates) as a Potential Indicator of
      Ocean Warming.
AB  - Among the planktonic dinoflagellates, the species-rich genus Neoceratium has
      particularly remarkable features that include its easily recognizable outline and
      large size. This ubiquitous genus shows consistent presence in all plankton
      samples and has been a model for numerous studies since the end of the 19th
      century. It has already been described as a good candidate to monitor water
      masses and describe ocean circulation. We argue that the sensitivity displayed by
      Neoceratium to water temperature also makes it relevant as an indicator of ocean
      warming. The advantages and interests of using Neoceratium species to monitor
      climate change on a large scale are reassessed in view of recent advances in
      understanding their biology and ecology.

PMID- 27694763
TI  - Biology of the Marine Heterotrophic Dinoflagellate Oxyrrhis marina: Current
      Status and Future Directions.
AB  - Heterotrophic dinoflagellates are prevalent protists in marine environments,
      which play an important role in the carbon cycling and energy flow in the marine
      planktonic community. Oxyrrhismarina (Dinophyceae), a widespread heterotrophic
      dinoflagellate, is a model species used for a broad range of ecological,
      biogeographic, and evolutionary studies. Despite the increasing research effort
      on this species, there lacks a synthesis of the existing data and a coherent
      picture of this organism. Here we reviewed the literature to provide an overview
      of what is known regarding the biology of O. marina, and identify areas where
      further studies are needed. As an early branch of the dinoflagellate lineage, O.
      marina shares similarity with typical dinoflagellates in permanent condensed
      chromosomes, less abundant nucleosome proteins compared to other eukaryotes,
      multiple gene copies, the occurrence of trans-splicing in nucleus-encoded mRNAs,
      highly fragmented mitochondrial genome, and disuse of ATG as a start codon for
      mitochondrial genes. On the other hand, O. marina also exhibits some distinct
      cytological features (e.g., different flagellar structure, absence of girdle and
      sulcus or pustules, use of intranuclear spindle in mitosis, presence of nuclear
      plaque, and absence of birefringent periodic banded chromosomal structure) and
      genetic features (e.g., a single histone-like DNA-associated protein, cob-cox3
      gene fusion, 5' oligo-U cap in the mitochondrial transcripts of protein-coding
      genes, the absence of mRNA editing, the presence of stop codon in the fused cob
      cox3 mRNA produced by post-transcriptional oligoadenylation, and vestigial
      plastid genes). The best-studied biology of this dinoflagellate is probably the
      prey and predators types, which include a wide range of organisms. On the other
      hand, the abundance of this species in the natural waters and its controlling
      factors, genome organization and gene expression regulation that underlie the
      unusual cytological and ecological characteristics are among the areas that
      urgently need study.

PMID- 27694767
TI  - An Updated List of Generic Names in the Thoracosphaeraceae.
AB  - Calcareous dinophytes produce exoskeletal calcified structures during their life
      history (a unique character among the alveolates) and are subsumed under the
      Thoracosphaeraceae as part of the Peridiniales. We provide a brief synopsis about
      the taxonomic history of the group, from the first descriptions of fossils in the
      19th century through to the results of molecular phylogenetics studies undertaken
      during the past two decades. Delimitation and circumscription of the
      Thoracosphaeraceae are challenging, as they comprise both phototrophic
      (presumably including endosymbiotic) as well as heterotrophic (and even
      parasitic) dinophytes from marine and freshwater environments, respectively.
      However, calcareous structures are not known from all members of the
      Thoracosphaeraceae, and the corresponding species and groups are considered to
      have lost the capacity to calcify. Five years ago, a taxonomic list of 99 generic
      names assigned to the Thoracosphaeraceae was published, and we update this
      compendium with 19 additional names based on recent studies.

PMID- 27694766
TI  - Elements in the Development of a Production Process for Modified Vaccinia Virus
      Ankara.
AB  - The production of several viral vaccines depends on chicken embryo fibroblasts or
      embryonated chicken eggs. To replace this logistically demanding substrate, we
      created continuous anatine suspension cell lines (CR and CR.pIX), developed
      chemically-defined media, and established production processes for different
      vaccine viruses. One of the processes investigated in greater detail was
      developed for modified vaccinia virus Ankara (MVA). MVA is highly attenuated for
      human recipients and an efficient vector for reactogenic expression of foreign
      genes. Because direct cell-to-cell spread is one important mechanism for vaccinia
      virus replication, cultivation of MVA in bioreactors is facilitated if cell
      aggregates are induced after infection. This dependency may be the mechanism
      behind our observation that a novel viral genotype (MVA-CR) accumulates with
      serial passage in suspension cultures. Sequencing of a major part of the genomic
      DNA of the new strain revealed point mutations in three genes. We hypothesize
      that these changes confer an advantage because they may allow a greater fraction
      of MVA-CR viruses to escape the host cells for infection of distant targets.
      Production and purification of MVA-based vaccines may be simplified by this
      combination of designed avian cell line, chemically defined media and the novel
      virus strain.

PMID- 27694768
TI  - A Novel Bioinformatics Strategy to Analyze Microbial Big Sequence Data for
      Efficient Knowledge Discovery: Batch-Learning Self-Organizing Map (BLSOM).
AB  - With the remarkable increase of genomic sequence data of microorganisms, novel
      tools are needed for comprehensive analyses of the big sequence data available.
      The self-organizing map (SOM) is an effective tool for clustering and visualizing
      high-dimensional data, such as oligonucleotide composition on one map. By
      modifying the conventional SOM, we developed batch-learning SOM (BLSOM), which
      allowed classification of sequence fragments (e.g., 1 kb) according to
      phylotypes, solely depending on oligonucleotide composition. Metagenomics studies
      of uncultivable microorganisms in clinical and environmental samples should allow
      extensive surveys of genes important in life sciences. BLSOM is most suitable for
      phylogenetic assignment of metagenomic sequences, because fragmental sequences
      can be clustered according to phylotypes, solely depending on oligonucleotide
      composition. We first constructed oligonucleotide BLSOMs for all available
      sequences from genomes of known species, and by mapping metagenomic sequences on
      these large-scale BLSOMs, we can predict phylotypes of individual metagenomic
      sequences, revealing a microbial community structure of uncultured
      microorganisms, including viruses. BLSOM has shown that influenza viruses
      isolated from humans and birds clearly differ in oligonucleotide composition.
      Based on this host-dependent oligonucleotide composition, we have proposed
      strategies for predicting directional changes of virus sequences and for
      surveilling potentially hazardous strains when introduced into humans from non
      human sources.

PMID- 27694765
TI  - Transcription and Maturation of mRNA in Dinoflagellates.
AB  - Dinoflagellates are of great importance to the marine ecosystem, yet scant
      details of how gene expression is regulated at the transcriptional level are
      available. Transcription is of interest in the context of the chromatin structure
      in the dinoflagellates as it shows many differences from more typical eukaryotic
      cells. Here we canvas recent transcriptome profiles to identify the molecular
      building blocks available for the construction of the transcriptional machinery
      and contrast these with those used by other systems. Dinoflagellates display a
      clear paucity of specific transcription factors, although surprisingly, the rest
      of the basic transcriptional machinery is not markedly different from what is
      found in the close relatives to the dinoflagellates.

PMID- 27694769
TI  - Control of a Multi-Drug-Resistant Acinetobacter baumannii Outbreak after
      Orthopedics Department Relocation.
AB  - Acinetobacter baumannii clinical isolates have the ability to survive in the
      hospital niche for prolonged time periods and to develop resistance against
      multiple antimicrobial agents. Therefore, A. baumannii has emerged as an
      important cause of nosocomial outbreaks worldwide, especially in critical-care
      environments such as intensive care units. In the present communication, we
      report a multi-drug-resistant A. baumannii outbreak that occurred in an
      orthopedics department in Greece after the admission of a patient previously
      hospitalized in the intensive care unit of a Greek tertiary care hospital.
      Despite the implementation of infection control measures, 29 patients were
      infected, significantly raising their hospitalization periods and treatment
      costs. Interestingly, the outbreak was put under control after the department's
      previously programmed relocation.

PMID- 27694770
TI  - Molecular Quantification and Genetic Diversity of Toxigenic Fusarium Species in
      Northern Europe as Compared to Those in Southern Europe.
AB  - Fusarium species produce important mycotoxins, such as deoxynivalenol (DON),
      nivalenol (NIV) and T-2/HT-2-toxins in cereals. The highest DON and T-2/HT-2
      toxin levels in northern Europe have been found in oats. About 12%-24% of Finnish
      oat samples in 2012 contained >1.75 mg.kg-1 of DON, which belongs to type B
      trichothecenes. Fusarium graminearum is the most important DON producer in
      northern Europe and Asia and it has been displacing the closely related F.
      culmorum in northern Europe. The 3ADON chemotype of F. graminearum is dominant in
      most northern areas, while the 15ADON chemotype of F. graminearum is
      predominating in Central and southern Europe. We suggest that the northern
      population of F. graminearum may be more specialized to oats than the southern
      population. Only low levels of F. culmorum DNA were found in a few oat samples
      and no correlation was found between F. culmorum DNA and DON levels. DNA levels
      of F. graminearum were in all cases in agreement with DON levels in 2011 and
      2012, when DON was measured by gas chromatography-mass spectrometry (GC-MS). When
      the RIDA(r)QUICK SCAN kit results (DON) were compared to DNA levels of F.
      graminearum, the variation was much higher. The homogenization of the oats flour
      by grinding oats with 1 mm sieve seems to be connected to this variation. There
      was a significant correlation between the combined T-2 and HT-2 and the combined
      DNA levels of F. langsethiae and F. sporotrichioides in Finland in 2010-2012.

PMID- 27694771
TI  - Macroalgal Endophytes from the Atlantic Coast of Canada: A Potential Source of
      Antibiotic Natural Products?
AB  - As the need for new and more effective antibiotics increases, untapped sources of
      biodiversity are being explored in an effort to provide lead structures for drug
      discovery. Endophytic fungi from marine macroalgae have been identified as a
      potential source of biologically active natural products, although data to
      support this is limited. To assess the antibiotic potential of temperate
      macroalgal endophytes we isolated endophytic fungi from algae collected in the
      Bay of Fundy, Canada and screened fungal extracts for the presence of
      antimicrobial compounds. A total of 79 endophytes were isolated from 7 species of
      red, 4 species of brown, and 3 species of green algae. Twenty of the endophytes
      were identified to the genus or species level, with the remaining isolates
      designated codes according to their morphology. Bioactivity screening assays
      performed on extracts of the fermentation broths and mycelia of the isolates
      revealed that 43 endophytes exhibited antibacterial activity, with 32 displaying
      antifungal activity. Endophytic fungi from Bay of Fundy macroalgae therefore
      represent a significant source of antibiotic natural products and warrant further
      detailed investigation.

PMID- 27694772
TI  - Temporal Variation of Mycotoxin Producing Fungi in Norwegian Cereals.
AB  - Spring barley is grown on about half of the Norwegian cereal area. The rest of
      the area is equally divided between wheat and oats. Most years the domestic
      production provides 70%-80% of the domestic market for bread wheat. Barley and
      oats are mainly grown for animal feed. During the years 2008-2012, severe
      epidemics of Fusarium head blight have led to increased mycotoxin contamination
      of cereals. During that period, precipitation was above normal during anthesis
      and grain maturation. The most important mycotoxin producers have been F.
      avenaceum, F. culmorum, F. graminearum and F. langsethiae. Increased
      deoxynivalenol contamination of Norwegian cereals during recent years is due to
      severe F. graminearum epidemics.

PMID- 27694773
TI  - Sad State of Phage Electron Microscopy. Please Shoot the Messenger.
AB  - Two hundred and sixty publications from 2007 to 2012 were classified according to
      the quality of electron micrographs; namely as good (71); mediocre (21); or poor
      (168). Publications were from 37 countries; appeared in 77 journals; and included
      micrographs produced with about 60 models of electron microscopes. The quality of
      the micrographs was not linked to any country; journal; or electron microscope.
      Main problems were poor contrast; positive staining; low magnification; and small
      image size. Unsharp images were frequent. Many phage descriptions were silent on
      virus purification; magnification control; even the type of electron microscope
      and stain used. The deterioration in phage electron microscopy can be attributed
      to the absence of working instructions and electron microscopy courses;
      incompetent authors and reviewers; and lenient journals. All these factors are
      able to cause a gradual lowering of standards.

PMID- 27694774
TI  - Towards an Ecological Understanding of Dinoflagellate Cyst Functions.
AB  - The life cycle of many dinoflagellates includes at least one nonflagellated
      benthic stage (cyst). In the literature, the different types of dinoflagellate
      cysts are mainly defined based on morphological (number and type of layers in the
      cell wall) and functional (long- or short-term endurance) differences. These
      characteristics were initially thought to clearly distinguish pellicle (thin
      walled) cysts from resting (double-walled) dinoflagellate cysts. The former were
      considered short-term (temporal) and the latter long-term (resting) cysts.
      However, during the last two decades further knowledge has highlighted the great
      intricacy of dinoflagellate life histories, the ecological significance of cyst
      stages, and the need to clarify the functional and morphological complexities of
      the different cyst types. Here we review and, when necessary, redefine the
      concepts of resting and pellicle cysts, examining both their structural and their
      functional characteristics in the context of the life cycle strategies of several
      dinoflagellate species.

PMID- 27694775
TI  - Emergence of Algal Blooms: The Effects of Short-Term Variability in Water Quality
      on Phytoplankton Abundance, Diversity, and Community Composition in a Tidal
      Estuary.
AB  - Algal blooms are dynamic phenomena, often attributed to environmental parameters
      that vary on short timescales (e.g., hours to days). Phytoplankton monitoring
      programs are largely designed to examine long-term trends and interannual
      variability. In order to better understand and evaluate the relationships between
      water quality variables and the genesis of algal blooms, daily samples were
      collected over a 34 day period in the eutrophic Lafayette River, a tidal
      tributary within Chesapeake Bay's estuarine complex, during spring 2006. During
      this period two distinct algal blooms occurred; the first was a cryptomonad bloom
      and this was followed by a bloom of the mixotrophic dinoflagellate, Gymnodinium
      instriatum. Chlorophyll a, nutrient concentrations, and physical and chemical
      parameters were measured daily along with phytoplankton abundance and community
      composition. While 65 phytoplankton species from eight major taxonomic groups
      were identified in samples and total micro- and nano-phytoplankton cell densities
      ranged from 5.8 * 106 to 7.8 * 107 cells L-1, during blooms, cryptomonads and G.
      instriatum were 91.6% and 99.0%, respectively, of the total phytoplankton biomass
      during blooms. The cryptomonad bloom developed following a period of rainfall and
      concomitant increases in inorganic nitrogen concentrations. Nitrate, nitrite and
      ammonium concentrations 0 to 5 days prior were positively lag-correlated with
      cryptomonad abundance. In contrast, the G. insriatum bloom developed during
      periods of low dissolved nitrogen concentrations and their abundance was
      negatively correlated with inorganic nitrogen concentrations.

PMID- 27694776
TI  - Effect of Electrical Stimulation on Fruit Body Formation in Cultivating
      Mushrooms.
AB  - The effect of high-voltage electrical stimulation on fruit body formation in
      cultivating mushrooms was evaluated using a compact pulsed power generator
      designed and based on an inductive energy storage system. An output voltage from
      50 to 130 kV with a 100 ns pulse width was used as the electrical stimulation to
      determine the optimum amplitude. The pulsed high voltage was applied to a sawdust
      based substrate of Lyophyllum decastes and natural logs hosting Lentinula edodes,
      Pholiota nameko, and Naematoloma sublateritium. The experimental results showed
      that the fruit body formation of mushrooms increased 1.3-2.0 times in terms of
      the total weight. The accumulated yield of Lentinula edodes for four cultivation
      seasons was improved from 160 to 320 g by applying voltages of 50 or 100 kV.
      However, the yield was decreased from 320 to 240 g upon increasing the applied
      voltage from 100 to 130 kV. The yield of the other types of mushrooms showed
      tendencies similar to those of Lentinula edodes when voltage was applied. An
      optimal voltage was confirmed for efficient fruit body induction. The hypha
      activity was evaluated by the amount of hydrophobin release, which was mainly
      observed before the fruit body formation. The hydrophobin release decreased for
      three hours after stimulation. However, the hydrophobin release from the
      vegetative hyphae increased 2.3 times one day after the stimulation.

PMID- 27694777
TI  - A Comparative Overview of the Flagellar Apparatus of Dinoflagellate, Perkinsids
      and Colpodellids.
AB  - Dinoflagellates are a member of the Alveolata, and elucidation of the early
      evolution of alveolates is important for our understanding of dinoflagellates,
      and vice versa. The ultrastructure of the flagellar apparatus has been described
      from several dinoflagellates in the last few decades, and the basic components
      appear to be well conserved. The typical dinoflagellate apparatus is composed of
      two basal bodies surrounded by striated collars attached to a connective fiber.
      The longitudinal basal body is connected to a longitudinal microtubular root
      (LMR; equivalent of R1) and single microtubular root (R2), whereas the transverse
      basal body is connected to a transverse microtubular root (TMR; R3) and
      transverse striated root (TSR) with a microtubule (R4). Some of these components,
      especially the connective fibers and collars, are dinoflagellate specific
      characteristics that make their flagellar apparatus relatively complex. We also
      compare these structures with the flagellar apparatus from a number of close
      relatives of dinoflagellates and their sister, the apicomplexans, including
      colpodellids, perkinsids, and Psammosa. Though the ultrastructural knowledge of
      these lineages is still relatively modest, it provides us with an interesting
      viewpoint of the character evolution of the flagellar apparatus among those
      lineages.

PMID- 27694778
TI  - Lubricin in synovial fluid of mild and severe temporomandibular joint internal
      derangements.
AB  - BACKGROUND: To understand the molecular basis of temporomandibular joint (TMJ)
      pathologies, we aimed to investigate the lubricin levels in the TMJ synovial
      fluid (SF) of patients with mild to severe internal derangements (IDs). MATERIAL
      AND METHODS: A total, 34 joints were the study group. Only patients, with a
      Wilkes stage of III, IV and V were included, in this sample. Control group
      consisted of SF from eight joints, from patients undergoing to orthognatic
      surgery. Concentrations of lubricin in the SF from both samples were measured
      using ELISA system. RESULTS: The mean lubricin concentration was 7.029 +/- 0.21
      ug/mL in stage III patients; 5.64 +/- 0.10 ug/mL in stage IV patients, and 4.78
      +/- 0.11 ug/mL in stage V patients. The lubricin levels from stage IV and stage V
      patients differed significantly (P <= 0.001) from those of control subjects.
      Lubricin levels were inversely correlated with age and to VAS score. CONCLUSIONS:
      The results of this cross-sectional study highlight the relationship between
      disease severity and the levels of lubricin in TMJ SF. Our findings suggest that
      novel biotherapeutic approaches, including the administration of recombinant
      lubricin in the joint cavity, for the treatment of TMJ diseases can be developed.

PMID- 27694779
TI  - Oral tongue cancer in public hospitals in Madrid, Spain (1990-2008).
AB  - BACKGROUND: The cancer which appears in the mobile portion of the tongue is the
      most common neoplasm of the oral cavity. The objective of this study was to
      analyse oral tongue cancer epidemiology in a population of 610 patients diagnosed
      between 1990 and 2008 and detailed in the Tumour Registry of the Madrid region.
      MATERIAL AND METHODS: A retrospective analysis based on the following variables
      provided in the Tumour Registry was achieved: age, gender, histology, stage,
      location, treatment. Descriptive and analytic statistics with these variables,
      using Pearson's Chi-square test to study the relationship between the qualitative
      variables. RESULTS: Patients' mean age was 61.53+/-13.95 years, with a gender
      ratio of 2.09:1 (413 males vs 197 females). The lesion was mainly localized in
      the lateral border of tongue, with other sites (dorsal face, ventral face,
      lingual tonsil, contiguous sites, tongue NOS) represented at lower rates.
      Squamous cell carcinomas (94.9%) far outweighted other histologies (salivary
      gland tumours, soft tissue tumours, haematolymphoid tumours). 59% of the cases
      appeared in localized stages, versus 35.2% in regional and 4.8% in distant
      stages. Surgery was the most frequently used treatment, followed by surgery in
      combination with radiotherapy. CONCLUSIONS: Oral tongue cancer is a disease of
      the elderly, with a male predominance. It mainly appears in its lateral border,
      localized squamous cell carcinomas representing the great majority of lingual
      neoplasms.

PMID- 27694780
TI  - Dabigatran: A new oral anticoagulant. Guidelines to follow in oral surgery
      procedures. A systematic review of the literature.
AB  - BACKGROUND: Dabigatran is a newly commercialized drug that is replacing other
      anticoagulants in the prevention of venous thromboembolism, stroke and systemic
      arterial valve embolism. It acts directly on thrombin presenting in a dynamic and
      predictable way, which does not require monitoring these patients. Therefore, we
      consider the need to assess whether their use increases the risk of bleeding
      involved before any dental treatment. MATERIAL AND METHODS: We performed a
      systematic review with a bibliographic search in PubMed/Medline along with the
      Cochrane Library. We excluded articles dealing with all anticoagulants other than
      dabigatran, and works about surgical treatments in anatomical locations other
      than the oral cavity. RESULTS: We included a total of 13 papers of which 1 was a
      randomized clinical trial, 9 narrative literature reviews, 1 case series, 2
      clinical cases and 1 expert opinion. Because we did not obtain any properly
      designed clinical trials, we were unable to conduct a meta-analysis. CONCLUSIONS:
      Currently, there is no consensus on the procedure to be followed in patients
      taking dabigatran. However, all authors agree to treat each case individually in
      accordance to the risk of embolism, postoperative bleeding and renal function.
      Also, it is necessary to perform minimally invasive interventions, and take the
      appropriate local anti-hemolytic measures.

PMID- 27694782
TI  - Temporomandibular chronic dislocation: The long-standing condition.
AB  - BACKGROUND: The temporomandibular joint (TMJ) dislocation can be categorised into
      three groups: acute, habitual or recurrent and long-standing. The long-standing
      or protracted lower jaw dislocation refers to a condition that persists for more
      than one month without reduction. There are a great variety of methods for its
      treatment, from the manual or non-surgical, to surgical ones like the indirect
      approach (conservative surgical approach) and direct approach (open joint).
      Additional procedures in unsuccessful cases may include extra-articular
      orthognathic techniques to correct a malocclusion until joint replacement.
      MATERIAL AND METHODS: We report four new cases with a minimum of 6 weeks
      dislocation who were seen since 1995 to 2015 in the Maxillofacial Department of
      the Clinico Hospital (Valencia, Spain), in which the mean age was 57.5 years.
      Most of them were bilateral and the gender was predominantly female.
      Additionally, we have reviewed the related literature. RESULTS: All of the cases
      were successfully treated and half of them required open surgery. CONCLUSIONS:
      The report confirms the difficulty of the treatment and reaffirms the necessity
      to bear in mind the wide variety of methods available for the treatment of this
      pathology. We stress the difficulties associated with managing the treatment and
      of suggesting new guidelines. The best option still remains not to delay the
      diagnostic and to select the appropriate initial treatment.

PMID- 27694781
TI  - Analysis of potential dynamic concealed factors in the difficulty of lower third
      molar extraction.
AB  - BACKGROUND: The purpose of this study was to identify potential concealed
      variables associated with the difficulty of lower third molar (M3) extractions.
      MATERIAL AND METHODS: To address the research purpose, we implemented a
      prospective study and enrolled a sample of subjects presenting for M3 removal.
      Predictor variables were categorized into Group-I and Group-II, based on
      predetermined criteria. The primary outcome variable was the difficulty of
      extraction, measured as extraction time. Appropriate univariate and multivariate
      statistics were computed using ordinal logistic regression. RESULTS: The sample
      comprised of 1235 subjects with a mean age of 29.49 +/- 8.92 years in Group-I and
      26.20 +/- 11.55 years in Group-II subjects. The mean operating time per M3
      extraction was 21.24 +/- 12.80 and 20.24 +/- 12.50 minutes for Group-I and Group
      II subjects respectively. Three linear parameters including B-M2 height (distance
      between imaginary point B on the inferior border of mandibular body, and M2),
      lingual cortical thickness, bone density and one angular parameter including Rc
      Cs angle (angle between ramus curvature and curve of spee), in addition to
      patient's age, profile type, facial type, cant of occlusal plane, and decreased
      overbite, were found to be statistically associated ( p < or = 0.05) with
      extraction difficulty under regression models. CONCLUSIONS: In conclusion, our
      study indicates that the difficulty of lower M3 extractions is possibly governed
      by morphological and biomechanical factors with substantial influence of
      myofunctional factors. PRACTICAL IMPLICATIONS: Preoperative evaluation of dynamic
      concealed factors may not only help in envisaging the difficulty and planning of
      surgical approach but might also help in better time management in clinical
      practice.

PMID- 27694783
TI  - Local vs general anaesthesia in the development of neurosensory disturbances
      after mandibular third molars extraction: A retrospective study of 534 cases.
AB  - BACKGROUND: The choice of the anaesthetic modality is one of the primary steps
      during planning of third molar surgery. The aim of the present study was to
      compare the risk of developing neurological injures of the inferior alveolar
      nerve (IAN) and lingual nerve (LN) in patients treated for wisdom teeth removal
      under general anaesthesia (GA) with a group treated under local anaesthesia (LA).
      MATERIAL AND METHODS: This is an observational retrospective, unicentric study;
      between September 2013 and September 2014, 534 patients underwent third molar
      surgery, 194 (36,3%) under GA and 340 (63,7%) under LA by the same oral surgeon.
      Difference in the incidence of IAN and LN injures between groups have been
      statistically analyzed with Fisher exact test and estimated odd ratio for
      development of such complications has been calculated. RESULTS: In GA patients
      the incidence of IAN and LN injures was 4.6% and 2.1%, respectively while in the
      LA group it was and 0.3% and 0%, respectively. A significant difference in IAN
      and LN involvement between groups was observed (IAN lesion: Fisher exact test,
      p<0.001; LN lesions: Fisher exact test, p<0.05). The estimated odd ratio for
      development of IAN injures after GA was 16.49 (95% CI: 2.07-131.19) and was not
      calculable for LN injures because no cases were observed in the LA group.
      CONCLUSIONS: Since GA is a perioperative variable that seems to significantly
      increase the risk of developing IAN and LN lesions, when treating patients that
      request GA, they must be adequately informed that an higher incidence of post
      surgical sensory disturbances is expected.

PMID- 27694784
TI  - Myogenic temporomandibular disorders: Clinical systemic comorbidities in a female
      population sample.
AB  - BACKGROUND: Myogenic temporomandibular disorders (MTMD) frequently coexist with
      other clinical conditions in the same individual. In the last decades, several
      authors have analyzed these comorbidities looking for the origin of this
      overlapping. Objetives: The aim of this study was to perform a comparative
      anaylisis between a group of patients with MTMD and a control group of dental
      patients without dysfunctional pathology to assess whether there are significant
      differences in the presence of systemic medical comorbidities between the two
      groups. MATERIAL AND METHODS: Restrospective epidemiological analysis, based on
      medical questionnaires in a group of 31 patients, women, aged from 24 to 58
      (average 39.96 years), diagnosed with MTMD (Masticatory Myofascial Pain), with a
      control group with the same number of individuals, gender and age range to
      evaluate if there is a significant statistical difference in the presence of
      medical comorbidities in this group of patients with MTMD and if they are in a
      higher risk of suffering different pathological conditions. RESULTS: It was found
      that the group affected by MTMD presented many more associated medical conditions
      than the control group: health changes during the last year, medical evaluations
      and treatments, presence of pain, sinus disease, tinnitus, headache, joint pain,
      ocular disorders, fatigue, dizziness, genitourinary disorders and xerostomia
      among others; and they were also in a higher risk to suffer other pathological
      entities as headaches and articular pain. CONCLUSIONS: These results reinforce
      our hypothesis that MTMD belong to a group of medical conditions triggered by a
      loss of equilibrium of the individual's Psycho-Neuro-Endocrine-Immune (PNEI) Axis
      that produces alterations in the response against external stimuli in some
      genetically predisposed individuals. It is, therefore, necessary to change the
      way of diagnosing and managing these individual's medical conditions, being
      mandatory to look from a more multidisciplinary perspective than the one we are
      currently offering.

PMID- 27694785
TI  - Retrospective study of the bone morphology in the posterior mandibular region.
      Evaluation of the prevalence and the degree of lingual concavity and their
      possible complications.
AB  - BACKGROUND: In order to choose the appropriate implant size and to prevent
      complications, an oral surgeon must know the size and shape of the mandible. In
      the posterior mandibular region, a lingual undercut is often found and could
      represent a difficulty hard to manage if a lingual or buccal perforation occur. A
      large series of computed tomography (CT) images of the mandibular first molar was
      evaluated and the bone morphology, the prevalence and the degree of the lingual
      concavity in the first molar region were studied. MATERIAL AND METHODS: One
      hundred and fifty-one computed tomography (CT) examinations of patients were
      retrospectively evaluated to determine anatomical variations in bone morphology
      in the submandibular fossa region. RESULTS: A total of 151 subjects were
      included, consisting of 64 males (M) (42.4%) and 87 females (F) (57.6%). The
      under-cut type ridge was present in 64.2% of the cases. The concavity angle was
      66.6 +/- 8.9 degrees  (M) and 71.6 +/- 8.4 degrees  (F) and the linear concavity
      depth 4.5 +/- 2.3 mm (M) and 3.1 +/- 1.7 mm (F) (p>0.05). CONCLUSIONS: Mandibles
      with any lingual concavity present a potential increased risk of lingual cortical
      perforation during implant placement surgery. CT imaging allows characterizing
      the anatomy of the submandibular fossa and provides other important information
      for the preoperative assessment of the posterior mandible for dental implants
      placement.

PMID- 27694786
TI  - Radial free forearm flap versus pectoralis major pedicled flap for reconstruction
      in patients with tongue cancer: Assessment of quality of life.
AB  - BACKGROUND: This study investigated the quality of life of Chinese patients with
      tongue cancer who had undergone immediate flap reconstruction surgery. In
      addition, we compared 2 groups of patients: those who had received radial forearm
      free flap (RFFF) surgery and others who had received pectoralis major
      myocutaneous flap (PMMF) surgery. MATERIAL AND METHODS: Patients who received
      RFFF or PMMF reconstruction after primary tongue cancer treated with total and
      subtotal tongue resection were eligible for the current study. The patients'
      demographic data, medical history, and quality of life scores (14-item Oral
      Health Impact Profile (OHIP-14) and the University of Washington Quality of Life
      (UW-QOL) questionnaires) were collected. RESULTS: A total of 41 of 63
      questionnaires were returned (65.08%). There were significant differences between
      the 2 groups in the gender (p< .05). Patients reconstructed with RFFF performed
      better in the shoulder domains, in addition to worse appearance domains.
      CONCLUSIONS: Using either RFFF or PMMF for reconstruction of defects after tongue
      cancer resection significantly influences a patient's quality of life. Data from
      this study provide useful information for physicians and patients during their
      discussion of reconstruction modalities for tongue cancers.

PMID- 27694787
TI  - Oral health and quality of life in the municipal senior citizen's social clubs
      for people over 65 of Valencia, Spain.
AB  - BACKGROUND: The world population is aging considerably. The state of elderly's
      dentition is poor. Many authors agree that the oral health status influence the
      elderly's quality of life.The objective of our study was to analyze the relation
      between the oral health status and the general health status through the quality
      of life of elderly people aged 65 years or more in Valencia, Spain. MATERIAL AND
      METHODS: A cross-sectional oral health survey and an oral examination have been
      designed to study an elderly population. There were 202 adults (103 men and 99
      women). Age: 65 years of age and over. Randomly selected senior citizen's social
      clubs. The Oral Health Impact Profile (OHIP-14) has been used to obtain the
      health survey. Moreover, the EuroQol-5d and a Visual Analogue Scale (VAS) have
      been the tools to obtain the general health status. Finally, sociodemographic and
      oral health questions have been needed. RESULTS: Descriptive and inferential
      results have been done and the main results are the following, the mean additive
      score of the OHIP-14 was 8.88, the mean value of the EuroQol-5d was 0.58 and of
      the VAS, 72.90. The OHIP-14 was consistently and significantly correlated with
      the index EuroQol-5d and with variables such as number of teeth, missing teeth,
      DMFT, dental status (being or not edentulous) and occupation. The EuroQol-5d was
      related to dental habits, sex, income, systemic pathologies and filled teeth.
      CONCLUSIONS: The oral health has a high impact on quality of life. The oral
      health and the general health are closely related. The oral hygiene and getting
      toothless influence negatively on the quality of life of elderly people.

PMID- 27694788
TI  - Impacted maxillary canines and root resorption of adjacent teeth: A retrospective
      observational study.
AB  - BACKGROUND: The prevalence of impacted maxillary canine is reported to be between
      1% and 3%. The lack of monitoring and the delay in the treatment of the impacted
      canine can cause different complications such as: displacement of adjacent teeth,
      loss of vitality of neighbouring teeth, shortening of the dental arch, follicular
      cysts, canine ankylosis, recurrent infections, recurrent pain, internal
      resorption of the canine and the adjacent teeth, external resorption of the
      canine and the adjacent teeth, combination of these factors. An appropriate
      diagnosis, accurate predictive analysis and early intervention are likely to
      prevent such undesirable effects. The objective is to evaluate, by means of a
      retrospective observational study, the possibility of carrying out a predictive
      analysis of root resorption adjacent to the impacted canines by means of
      orthopantomographs, so as to limit the prescription of additional 3D radiography.
      MATERIAL AND METHODS: 120 subjects with unilateral or bilateral maxillary
      impacted canine were examined and 50 patients with 69 impacted maxillary canine
      (22 male, 28 female; mean age: 11.7 years) satisfied the inclusion criteria of
      the study. These patients were subjected to a basic clinical and radiographic
      investigation (orthopantomographs and computerized tomography). All panoramic
      films were viewed under standardized conditions for the evaluation of two main
      variables: maxillary canine angulations (a, b, g angles) and the overlapping
      between the impacted teeth and the lateral incisor (Analysis of Lindauer). Binary
      logistic regression was used to estimate the likelihood of resorbed lateral
      incisors depending on sector location and angle measurements. RESULTS: Results
      indicated that b angle has the greatest influence on the prediction of root
      resorption (predictive value of b angle = 76%). If beta angle <18 degrees  and
      Lindauer = I, the probability of resorption is 0.06. CONCLUSIONS: Evaluation of b
      angle and superimposition lateral incisor/impacted canine analysed on
      orthopantomographs could be one of the evaluation criteria for prescribing second
      level examination (CT and CTCB) and for detecting root resorption of impacted
      maxillary canine adjacent teeth.

PMID- 27694789
TI  - Surgical complications in zygomatic implants: A systematic review.
AB  - BACKGROUND: The use of zygomatic implants in the prosthetic rehabilitation of the
      patient with severe maxillary bone atrophy is another therapeutic alternative,
      not exempt from complications. The main objective of this review is to analyze
      and describe the most frequent surgical complications associated with the use of
      zygomatic implants. MATERIAL AND METHODS: An electronic database search on
      PubMed, along with a manual search, without taking into account date nor
      language, was undertaken by two observers, selecting studies that comprised a
      study period from 6 to 12 months, any type of clinical trial, and series that
      included a follow-up and/or review period during the aforementioned margin, that
      mentioned at least two types of complications. RESULTS: Out of the initial search
      that yielded 455 studies, 67 were considered potentially relevant for the present
      study, out of which 14 were finally selected. Out of the most frequent surgical
      complications, sinusitis (3,9%) and failure in osseointegration (2,44%) are
      highlighted. CONCLUSIONS: The analysis of the results shows that the most
      frequent complications are sinusitis and failure in osseointegration of the
      zygomatic implant. However, a standardised data collection system for the data on
      complications is needed.

PMID- 27694790
TI  - Distance of the alveolar antral artery from the alveolar crest. Related factors
      and surgical considerations in sinus floor elevation.
AB  - BACKGROUND: In a variable proportion of maxillary sinuses alveolar antral artery
      is located close to the residual ridge, increasing the chances for haemorrhagic
      complications during sinus floor elevation procedures. MATERIAL AND METHODS:
      Retrospective observational study of CBCT explorations performed for implant
      treatment planning. The upper first molar area was selected for this study. The
      relative uncertainty (standard deviation of the measurement divided by its mean
      and expressed as a percentage from 0% to 100%) was chosen for determining the
      observational errors. For modeling the chances of AAA detection, the generalized
      additive models (GAM) approach was chosen. RESULTS: A total of 240 maxillary
      sinuses were studied (46.25% males) whose median median age was 58 years old
      (IQR: 52-66). Univariate models showed that the chances for an AAA-alvelar crest
      distance <=15mm increase in wider sinuses with lower, subsinusally edentulous
      crests. When distance is considered as a continuous variable, the best
      mutivariate model showed an explained deviance of 67% and included AAA diameter,
      distance AAA-sinus floor, sinus width, and shape, height and width of the
      residual ridge. Thinner AAAs are found closer to the crest (within the <=15mm
      safe distance). CONCLUSIONS: Bearing in mind the inclusion criteria and the
      limitations of this investigation, it is concluded that there is a high
      proportion of maxillary sinuses where AAA describes a course close to the
      alveolar crest (<=15mm), which was classically considered a safe distance for
      SFE. This position is related to the presence of atrophic crests (depressed ridge
      form) and wide maxillary sinuses where the distance of the vessel to the floor of
      the sinus is small. This information may permit a better surgical planning of SFE
      procedures.

PMID- 27694791
TI  - Cancer and orofacial pain.
AB  - BACKGROUND: Cancer pain is a devastating condition. Pain in the orofacial region,
      may be present as the single symptom of cancer or as a symptom of cancer in its
      later stages. This manuscript revises in a comprehensive manner the content of
      the conference entitled "Orofacial Pain and Cancer" (Dolor Orofacial y Cancer)
      given at the VI Simposio International "Advances in Oral Cancer" on the 22 July,
      2016 in San Sebastioan-Donostia, Spain. MATERIAL AND METHODS: We have reviewed
      (pubmed-medline) from the most relevant literature including reviews, systematic
      reviews and clinical cases, the significant and evidence-based mechanisms and
      mediators of cancer-associated facial pain, the diverse types of cancers that can
      be present in the craniofacial region locally or from distant sites that can
      refer to the orofacial region, cancer therapy that may induce pain in the
      orofacial region as well as discussed some of the new advancements in cancer pain
      therapy. RESULTS: There is still a lack of understanding of cancer pain
      pathophysiology since depends of the intrinsic heterogeneity, type and anatomic
      location that the cancer may present, making more challenging the creation of
      better therapeutic options. Orofacial pain can arise from regional or distant
      tumor effects or as a consequence of cancer therapy. CONCLUSIONS: The clinician
      needs to be aware that the pain may present the characteristics of any other
      orofacial pain disorder so a careful differential diagnosis needs to be given.
      Cancer pain diagnosis is made by exclusion and only can be reached after a
      thorough medical history, and all the common etiologies have been carefully
      investigated and ruled out. The current management tools are not optimal but
      there is hope for new, safer and effective therapies coming in the next years.

PMID- 27694792
TI  - Effect of miRNA-27a and Leptin Polymorphisms on Risk of Recurrent Spontaneous
      Abortion.
AB  - BACKGROUND The aim of this study was to investigate the possible associations of
      miRNA-27a and Leptin polymorphisms with the risk of recurrent spontaneous
      abortion (RSA). MATERIAL AND METHODS Between May 2013 and April 2015 at Shenzhen
      Longhua New District Central Hospital, we randomly recruited 138 RSA patients as
      the case group and another 142 normal pregnancy women as the control group. We
      used denaturing high-performance liquid chromatography (DHPLC) to determine the
      genotypes and allele frequencies of miRNA-27a rs895819 A/G and Leptin rs7799039
      G/A. RESULTS The GG genotype and G allele frequencies of miRNA-27a rs895819 A/G
      were higher in the case group than in the control group, and the AA genotype and
      A allele frequencies of Leptin rs7799039 G/A were also higher in the case group
      than in the control group (all P<0.05). MiRNA-27a rs895819 A/G and Leptin
      rs7799039 G/A polymorphisms increased the risk of RSA (Exp (B)=2.732, 95%
      CI=1.625~4.596, P=0.000; Exp (B)=4.081, 95% CI=1.817~9.164, P=0.001). GG-AA or AG
      AA carriers had a higher risk of RSA. The miRNA-27a expression of AA carriers of
      miRNA-27a rs895819 was lower than that of AG+GG carriers both in the case and
      control groups (all P=0.024). The plasma leptin concentration of GG carriers was
      lower than that of GA+AA carriers in the case group (P=0.026). CONCLUSIONS The
      polymorphisms of miRNA-27a rs895819 A/G and Leptin rs7799039 G/A may contribute
      to an increased risk of RSA.

PMID- 27694793
TI  - Y-27632 Increases Sensitivity of PANC-1 Cells to EGCG in Regulating Cell
      Proliferation and Migration.
AB  - BACKGROUND The study aimed to investigate the inhibitory effect of (1R,4r)-4-((R)
      1-aminoethyl)-N-(pyridin-4-yl) cyclohexanecarboxamide (Y-27632) and (-)
      epigallocatechin-3-gallate (EGCG) on the proliferation and migration of PANC-1
      cells. EGCG, found in green tea, has been previously shown to be one of the most
      abundant and powerful catechins in cancer prevention and treatment. Y-27632, a
      selective inhibitor of rho-associated protein kinase 1, is widely used in
      treating cardiovascular disease, inflammation, and cancer. MATERIAL AND METHODS
      PANC-1 cells, maintained in Dulbecco's Modified Eagle's Medium, were treated with
      dimethyl sulfoxide (control) as well as different concentrations (20, 40, 60, and
      80 MUg/mL) of EGCG for 48 h. In addition, PANC-1 cells were treated separately
      with 60 MUg/mL EGCG, 20 MUM Y-27632, and EGCG combined with Y-27632 (60 MUg/mL
      EGCG + 20 MUM Y-27632) for 48 h. The effect of EGCG and Y-27632 on the
      proliferation and migration of PANC-1 cells was evaluated using Cell Counting Kit
      8 and transwell migration assays. The expression of peroxisome proliferator
      activated receptor alpha (PPARalpha) and Caspase-3 mRNA was determined by
      Quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS EGCG (20-80
      MUg/mL) inhibited cell viability in a dose-dependent manner. Y-27632 enhanced the
      sensitivity of PANC-1 cells to EGCG (by increasing the expression of PPARa and
      Caspase-3 mRNA) and suppressed cell proliferation. PANC-1 cell migration was
      inhibited by treatment with a combination of EGCG and Y-27632. CONCLUSIONS Y
      27632 increases the sensitivity of PANC-1 cells to EGCG in regulating cell
      proliferation and migration, which is likely to be related to the expression of
      PPARa mRNA and Caspase-3 mRNA.

PMID- 27694794
TI  - Long Non-Coding RNA (LncRNA) Urothelial Carcinoma Associated 1 (UCA1) Increases
      Multi-Drug Resistance of Gastric Cancer via Downregulating miR-27b.
AB  - BACKGROUND In this study, we aimed to investigate the association between UCA1
      and miR-27b in gastric cancer and further study their involvement in multi-drug
      resistance (MDR) of gastric cancer. MATERIAL AND METHODS The microarray data of
      dysregulated lncRNAs in gastric cancer tissues was retrieved in the GEO dataset.
      QRT-PCR analysis was performed to assess UCA1 expression based on 28 paired
      cancerous and peritumoral normal tissues. The human gastric cancer cell line SGC
      7901, and SGC-7901 derived Adriamycin (doxorubicin) resistant SGC-7901/ADR,
      cisplatin resistant SGC-7901/DDP, and 5-FU resistant SGC-7901/FU cells were used
      as in vitro cell models to assess the effect of UCA1 and miR-27b on MDR. RESULTS
      UCA1 was significantly upregulated in the cancerous tissues and its expression
      was negatively correlated with miR-27b expression level. Inhibition of UCA1
      significantly restored miR-27b expression in MDR gastric cancer cells. UCA1
      knockdown and miR-27b overexpression reduced IC50 of ADR, DDP, and 5-FU in SGC
      7901/ADR cells and increased ADR induced cell apoptosis. UCA1 overexpression and
      miR-27b inhibition increased the IC50 of ADR, DDP, and 5-FU in SGC-7901 cells and
      reduced ADR induced cell apoptosis. Western blot analysis showed that UCA1
      knockdown and miR-27b overexpression also decreased anti-apoptotic protein BCL-2
      and increased apoptotic protein cleaved caspase-3. CONCLUSIONS UCA1 is negatively
      correlated with miR-27b expression in gastric cancer tissue. Knockdown of UCA1
      restored miR-27b expression in gastric cancer cells. The UCA1-miR-27b axis was
      involved in regulation of chemosensitivity of gastric cancer cells.

PMID- 27694795
TI  - Valve-in-Valve Replacement Using a Sutureless Aortic Valve.
AB  - BACKGROUND We present a unique case of a 61-year-old female patient with
      homograft deterioration after redo surgery for prosthetic valve endocarditis with
      root abscess. CASE REPORT The first operation was performed for type A dissection
      with root, arch, and elephant trunk replacement of the thoracic aorta. The
      present re-redo surgery was performed as valve-in-valve with a sutureless aortic
      bioprosthesis. The postoperative course was uneventful and the patient was
      discharged on day 6. CONCLUSIONS The current case report demonstrates that
      sutureless bioprostheses are an attractive option for surgical valve-in-valve
      procedures, which can reduce morbidity and mortality.

PMID- 27694796
TI  - Mild Hypothermia Protects Pigs' Gastric Mucosa After Cardiopulmonary
      Resuscitation via Inhibiting Interleukin 6 (IL-6) Production.
AB  - BACKGROUND The purpose of this study was to determine the effect of mild
      hypothermia therapy on gastric mucosa after cardiopulmonary resuscitation (CPR)
      and the underlying mechanism. MATERIAL AND METHODS Ventricular fibrillation was
      induced in pigs. After CPR, the surviving pigs were divided into mild hypothermia
      treated and control groups. The changes in vital signs and hemodynamic parameters
      were monitored before cardiac arrest and at intervals of 0.5, 1, 2, 4, 6, 12, and
      24 h after restoration of spontaneous circulation. Serum IL-6 was determined at
      the same time, and gastroscopy was performed. The pathologic changes were noted,
      and the expression of IL-6 was determined by hematoxylin and eosin (HE) staining
      and immunohistochemistry under light. RESULTS The heart rate, mean arterial blood
      pressure, and cardiac output in both groups did not differ significantly. The
      gastric mucosa ulcer index evaluated by gastroscopy 2 h and 24 h after
      restoration of spontaneous circulation (ROSC) in the mild hypothermic group was
      lower than that the control group (P<0.05). The inflammatory pathologic score of
      gastric mucosa in the mild hypothermic group 6-24 h after ROSC was lower than
      that in the control group (P<0.05). Serum and gastric mucosa IL-6 expression 0.5
      4 h and 6, 12, and 24 h after ROSC was lower in the mild hypothermic group than
      in the control group (P<0.05). CONCLUSIONS Mild hypothermia treatment protects
      gastric mucosa after ROSC via inhibiting IL-6 production and relieving the
      inflammatory reaction.

PMID- 27694797
TI  - Excess of mutational jackpot events in expanding populations revealed by spatial
      Luria-Delbruck experiments.
AB  - The genetic diversity of growing cellular populations, such as biofilms, solid
      tumours or developing embryos, is thought to be dominated by rare, exceptionally
      large mutant clones. Yet, the emergence of these mutational jackpot events is
      only understood in well-mixed populations, where they stem from mutations that
      arise during the first few cell divisions. To study jackpot events in spatially
      structured populations, we track mutant clones in microbial populations using
      fluorescence microscopy and population sequencing. High-frequency mutations are
      found to be massively enriched in microbial colonies compared with well-shaken
      liquid cultures, as a result of late-occurring mutations surfing at the edge of
      range expansions. Thus, jackpot events can be generated not only when mutations
      arise early but also when they occur at favourable locations, which exacerbates
      their role in adaptation and disease. In particular, because spatial competition
      with the wild type keeps most mutant clones in a quiescent state, strong
      selection pressures that kill the wild type promote drug resistance.

PMID- 27694798
TI  - Interference-driven spacer acquisition is dominant over naive and primed
      adaptation in a native CRISPR-Cas system.
AB  - CRISPR-Cas systems provide bacteria with adaptive immunity against foreign
      nucleic acids by acquiring short, invader-derived sequences called spacers. Here,
      we use high-throughput sequencing to analyse millions of spacer acquisition
      events in wild-type populations of Pectobacterium atrosepticum. Plasmids not
      previously encountered, or plasmids that had escaped CRISPR-Cas targeting via
      point mutation, are used to provoke naive or primed spacer acquisition,
      respectively. The origin, location and order of spacer acquisition show that
      spacer selection through priming initiates near the site of CRISPR-Cas
      recognition (the protospacer), but on the displaced strand, and is consistent
      with 3'-5' translocation of the Cas1:Cas2-3 acquisition machinery. Newly acquired
      spacers determine the location and strand specificity of subsequent spacers and
      demonstrate that interference-driven spacer acquisition ('targeted acquisition')
      is a major contributor to adaptation in type I-F CRISPR-Cas systems. Finally, we
      show that acquisition of self-targeting spacers is occurring at a constant rate
      in wild-type cells and can be triggered by foreign DNA with similarity to the
      bacterial chromosome.

PMID- 27694799
TI  - Enzymatic hydrolysis by transition-metal-dependent nucleophilic aromatic
      substitution.
AB  - Nitroaromatic compounds are typically toxic and resistant to degradation.
      Bradyrhizobium species strain JS329 metabolizes 5-nitroanthranilic acid (5NAA),
      which is a molecule secreted by Streptomyces scabies, the plant pathogen
      responsible for potato scab. The first biodegradation enzyme is 5NAA
      aminohydrolase (5NAA-A), a metalloprotease family member that converts 5NAA to 5
      nitrosalicylic acid. We characterized 5NAA-A biochemically and obtained snapshots
      of its mechanism. 5NAA-A, an octamer that can use several divalent transition
      metals for catalysis in vitro, employs a nucleophilic aromatic substitution
      mechanism. Unexpectedly, the metal in 5NAA-A is labile but is readily loaded in
      the presence of substrate. 5NAA-A is specific for 5NAA and cannot hydrolyze other
      tested derivatives, which are likewise poor inhibitors. The 5NAA-A structure and
      mechanism expand our understanding of the chemical ecology of an agriculturally
      important plant and pathogen, and will inform bioremediation and biocatalytic
      approaches to mitigate the environmental and ecological impact of nitroanilines
      and other challenging substrates.

PMID- 27694801
TI  - Polyketide and nonribosomal peptide retro-biosynthesis and global gene cluster
      matching.
AB  - Polyketides (PKs) and nonribosomal peptides (NRPs) are profoundly important
      natural products, forming the foundations of many therapeutic regimes. Decades of
      research have revealed over 11,000 PK and NRP structures, and genome sequencing
      is uncovering new PK and NRP gene clusters at an unprecedented rate. However,
      only ~10% of PK and NRPs are currently associated with gene clusters, and it is
      unclear how many of these orphan gene clusters encode previously isolated
      molecules. Therefore, to efficiently guide the discovery of new molecules, we
      must first systematically de-orphan emergent gene clusters from genomes. Here we
      provide to our knowledge the first comprehensive retro-biosynthetic program,
      generalized retro-biosynthetic assembly prediction engine (GRAPE), for PK and NRP
      families and introduce a computational pipeline, global alignment for natural
      products cheminformatics (GARLIC), to uncover how observed biosynthetic gene
      clusters relate to known molecules, leading to the identification of gene
      clusters that encode new molecules.

PMID- 27694800
TI  - Functional mining of transporters using synthetic selections.
AB  - Only 25% of bacterial membrane transporters have functional annotation owing to
      the difficulty of experimental study and of accurate prediction of their
      function. Here we report a sequence-independent method for high-throughput mining
      of novel transporters. The method is based on ligand-responsive biosensor systems
      that enable selective growth of cells only if they encode a ligand-specific
      importer. We developed such a synthetic selection system for thiamine
      pyrophosphate and mined soil and gut metagenomes for thiamine-uptake functions.
      We identified several members of a novel class of thiamine transporters, PnuT,
      which is widely distributed across multiple bacterial phyla. We demonstrate that
      with modular replacement of the biosensor, we could expand our method to xanthine
      and identify xanthine permeases from gut and soil metagenomes. Our results
      demonstrate how synthetic-biology approaches can effectively be deployed to
      functionally mine metagenomes and elucidate sequence-function relationships of
      small-molecule transport systems in bacteria.

PMID- 27694803
TI  - Cbr1 is a Dph3 reductase required for the tRNA wobble uridine modification.
AB  - Diphthamide and the tRNA wobble uridine modifications both require diphthamide
      biosynthesis 3 (Dph3) protein as an electron donor for the iron-sulfur clusters
      in their biosynthetic enzymes. Here, using a proteomic approach, we identified
      Saccharomyces cerevisiae cytochrome b5 reductase (Cbr1) as a NADH-dependent
      reductase for Dph3. The NADH- and Cbr1-dependent reduction of Dph3 may provide a
      regulatory linkage between cellular metabolic state and protein translation.

PMID- 27694802
TI  - Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor
      cells.
AB  - Asparagine (N)-linked glycosylation is a protein modification critical for
      glycoprotein folding, stability, and cellular localization. To identify small
      molecules that inhibit new targets in this biosynthetic pathway, we initiated a
      cell-based high-throughput screen and lead-compound-optimization campaign that
      delivered a cell-permeable inhibitor, NGI-1. NGI-1 targets
      oligosaccharyltransferase (OST), a hetero-oligomeric enzyme that exists in
      multiple isoforms and transfers oligosaccharides to recipient proteins. In non
      small-cell lung cancer cells, NGI-1 blocks cell-surface localization and
      signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but
      selectively arrests proliferation in only those cell lines that are dependent on
      EGFR (or fibroblast growth factor, FGFR) for survival. In these cell lines, OST
      inhibition causes cell-cycle arrest accompanied by induction of p21,
      autofluorescence, and cell morphology changes, all hallmarks of senescence. These
      results identify OST inhibition as a potential therapeutic approach for treating
      receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for
      reversibly regulating N-linked glycosylation in mammalian cells.

PMID- 27694805
TI  - Transfer of optical orbital angular momentum to a bound electron.
AB  - Photons can carry angular momentum, not only due to their spin, but also due to
      their spatial structure. This extra twist has been used, for example, to drive
      circular motion of microscopic particles in optical tweezers as well as to create
      vortices in quantum gases. Here we excite an atomic transition with a vortex
      laser beam and demonstrate the transfer of optical orbital angular momentum to
      the valence electron of a single trapped ion. We observe strongly modified
      selection rules showing that an atom can absorb two quanta of angular momentum
      from a single photon: one from the spin and another from the spatial structure of
      the beam. Furthermore, we show that parasitic ac-Stark shifts from off-resonant
      transitions are suppressed in the dark centre of vortex beams. These results show
      how light's spatial structure can determine the characteristics of light-matter
      interaction and pave the way for its application and observation in other
      systems.

PMID- 27694804
TI  - N-acetylglucosamine sensing by a GCN5-related N-acetyltransferase induces
      transcription via chromatin histone acetylation in fungi.
AB  - N-acetylglucosamine (GlcNAc) exists ubiquitously as a component of the surface on
      a wide range of cells, from bacteria to humans. Many fungi are able to utilize
      environmental GlcNAc to support growth and induce cellular development, a
      property important for their survival in various host niches. However, how the
      GlcNAc signal is sensed and subsequently transduced is largely unknown. Here, we
      identify a gene that is essential for GlcNAc signalling (NGS1) in Candida
      albicans, a commensal and pathogenic yeast of humans. Ngs1 can bind GlcNAc
      through the N-terminal beta-N-acetylglucosaminidase homology domain. This binding
      activates N-acetyltransferase activity in the C-terminal GCN5-related N
      acetyltransferase domain, which is required for GlcNAc-induced promoter histone
      acetylation and transcription. Ngs1 is targeted to the promoters of GlcNAc
      inducible genes constitutively by the transcription factor Rep1. Ngs1 is
      conserved in diverse fungi that have GlcNAc catabolic genes. Thus, fungi use Ngs1
      as a GlcNAc-sensor and transducer for GlcNAc-induced transcription.

PMID- 27694806
TI  - Dog and human inflammatory bowel disease rely on overlapping yet distinct
      dysbiosis networks.
AB  - Inflammatory bowel disease (IBD) is an autoimmune condition that is difficult to
      diagnose, and animal models of this disease have questionable human relevance1.
      Here, we show that the dysbiosis network underlying IBD in dogs differs from that
      in humans, with some bacteria such as Fusobacterium switching roles between the
      two species (as Bacteroides fragilis switches roles between humans and mice)2.
      For example, a dysbiosis index trained on humans fails when applied to dogs, but
      a dog-specific dysbiosis index achieves high correlations with the overall dog
      microbial community diversity patterns. In addition, a random forest classifier
      trained on dog-specific samples achieves high discriminatory power, even when
      using stool samples rather than the mucosal biopsies required for high
      discriminatory power in humans2. These relationships were not detected in
      previously published dog IBD data sets due to their limited sample size and
      statistical power3. Taken together, these results reveal the need to train host
      specific dysbiosis networks and point the way towards a generalized understanding
      of IBD across different mammalian models.

PMID- 27694807
TI  - Methylotrophic methanogenesis discovered in the archaeal phylum
      Verstraetearchaeota.
AB  - Methanogenesis is the primary biogenic source of methane in the atmosphere and a
      key contributor to climate change. The long-standing dogma that methanogenesis
      originated within the Euryarchaeota was recently challenged by the discovery of
      putative methane-metabolizing genes in members of the Bathyarchaeota, suggesting
      that methanogenesis may be more phylogenetically widespread than currently
      appreciated. Here, we present the discovery of divergent methyl-coenzyme M
      reductase genes in population genomes recovered from anoxic environments with
      high methane flux that belong to a new archaeal phylum, the Verstraetearchaeota.
      These archaea encode the genes required for methylotrophic methanogenesis, and
      may conserve energy using a mechanism similar to that proposed for the obligate
      H2-dependent methylotrophic Methanomassiliicoccales and recently described
      Candidatus 'Methanofastidiosa'. Our findings indicate that we are only beginning
      to understand methanogen diversity and support an ancient origin for methane
      metabolism in the Archaea, which is changing our understanding of the global
      carbon cycle.

PMID- 27694808
TI  - Genetic engineering: Allele-specific genome editing of disease loci.

PMID- 27694810
TI  - Metagenomics: Marine genomics goes viral.

PMID- 27694811
TI  - Dairy and plant based food intakes are associated with altered faecal microbiota
      in 2 to 3 year old Australian children.
AB  - The first 1000 days (conception to 24 months) is when gut microbiota composition
      and eating patterns are established, and a critical period influencing lifelong
      health. The aim of this study is to examine the associations between food intakes
      and microbiota composition at the end of this period. Diet was quantified for 37
      well-nourished Australian children aged between 2 to 3 years by using a food
      frequency questionnaire and 24 hr recalls. Both dairy and plant-based (fruit,
      vegetables, soy, pulses and nuts) food intakes were associated with distinct
      microbiota profiles. Dairy intake was positively associated with the
      Firmicutes:Bacteroidetes ratio, and in particular Erysipelatoclostridium spp.,
      but negatively associated with species richness and diversity. Vegetable intake
      was positively associated with the relative abundance of the Lachnospira genus,
      while soy, pulse and nut intake was positively associated with the relative
      abundance of bacteria related to Bacteroides xylanisolvens. Fruit intake,
      especially apples and pears, were negatively associated with the relative
      abundance of bacteria related to Ruminococcus gnavus. In this cohort of young
      children dairy and plant based food intakes were found to be associated with
      altered microbiota composition. Further exploration is needed to elucidate the
      effect of these dietary and microbial differences on host phenotype.

PMID- 27694809
TI  - Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA
      modifications.
AB  - Once deemed heretical, emerging evidence now supports the notion that the
      inheritance of acquired characteristics can occur through ancestral exposures or
      experiences and that certain paternally acquired traits can be 'memorized' in the
      sperm as epigenetic information. The search for epigenetic factors in mammalian
      sperm that transmit acquired phenotypes has recently focused on RNAs and, more
      recently, RNA modifications. Here, we review insights that have been gained from
      studying sperm RNAs and RNA modifications, and their roles in influencing
      offspring phenotypes. We discuss the possible mechanisms by which sperm become
      acquisitive following environmental-somatic-germline interactions, and how they
      transmit paternally acquired phenotypes by shaping early embryonic development.

PMID- 27694813
TI  - Characterization of Toxin Genes and Antimicrobial Susceptibility of
      Staphylococcus aureus Isolates in Fishery Products in Iran.
AB  - Staphylococcus aureus is one of the most common causes of seafood-borne diseases
      worldwide, which are attributable to the contamination of food by preformed
      enterotoxins. In this study, a total of 206 (34.3%) Staphylococcus aureus strains
      were obtained from 600 fish and shrimp samples and were tested for their
      antimicrobial susceptibility. We assessed the prevalence of the genes responsible
      for the staphylococcal enterotoxins (SEA, SEB) and toxic shock syndrome toxin 1
      (TSST-1) genes. The results indicated that 34% of aqua food samples were
      contaminated with S. aureus, and 23.8% of these isolates were mec-A-positive.
      Sixty-four percent of the strains isolated from contaminated seafood was
      enterotoxigenic S. aureus, and 28.2% of SEs were MRSA-positive. The most
      prevalent genotype was characterized by the presence of the sea gene (45.2%),
      followed by the seb gene (18.5%), and the tst gene encoding TSST-1 was found in
      eight strains (3.9%). Of the 206 S. aureus isolates, 189 strains (84.9%) were
      resistant to at least one antibiotic. Given the frequent outbreaks of
      enterotoxigenic MRSA, it is necessary to make revisions to mandatory programmes
      to facilitate improved hygiene practices during fishing, aquaculture, processing,
      and sales to prevent the contamination of fishery products in Iran.

PMID- 27694812
TI  - A plasma membrane microdomain compartmentalizes ephrin-generated cAMP signals to
      prune developing retinal axon arbors.
AB  - The development of neuronal circuits is controlled by guidance molecules that are
      hypothesized to interact with the cholesterol-enriched domains of the plasma
      membrane termed lipid rafts. Whether such domains enable local intracellular
      signalling at the submicrometre scale in developing neurons and are required for
      shaping the nervous system connectivity in vivo remains controversial. Here, we
      report a role for lipid rafts in generating domains of local cAMP signalling in
      axonal growth cones downstream of ephrin-A repulsive guidance cues. Ephrin-A
      dependent retraction of retinal ganglion cell axons involves cAMP signalling
      restricted to the vicinity of lipid rafts and is independent of cAMP modulation
      outside of this microdomain. cAMP modulation near lipid rafts controls the
      pruning of ectopic axonal branches of retinal ganglion cells in vivo, a process
      requiring intact ephrin-A signalling. Together, our findings indicate that lipid
      rafts structure the subcellular organization of intracellular cAMP signalling
      shaping axonal arbors during the nervous system development.

PMID- 27694814
TI  - Ultrastable glasses portray similar behaviour to ordinary glasses at high
      pressure.
AB  - Pressure experiments provide a unique opportunity to unravel new insights into
      glass-forming liquids by exploring its effect on the dynamics of viscous liquids
      and on the evolution of the glass transition temperature. Here we compare the
      pressure dependence of the onset of devitrification, Ton, between two molecular
      glasses prepared from the same material but with extremely different ambient
      pressure kinetic and thermodynamic stabilities. Our data clearly reveal that,
      while both glasses exhibit different dTon/dP values at low pressures, they evolve
      towards closer calorimetric devitrification temperature and pressure dependence
      as pressure increases. We tentatively interpret these results from the different
      densities of the starting materials at room temperature and pressure. Our data
      shows that at the probed pressures, the relaxation time of the glass into the
      supercooled liquid is determined by temperature and pressure similarly to the
      behaviour of liquids, but using stability-dependent parameters.

PMID- 27694815
TI  - Correlation of serum hepcidin levels with disease progression in hepatitis B
      virus-related disease assessed by nanopore film based assay.
AB  - Chronic hepatitis B virus (HBV) infection often develop into cirrhosis, and both
      are major risk factors of hepatocellular carcinoma. However, effective approaches
      for the monitoring of HBV-related disease progress are still in need. Increased
      iron storage has an important role in HBV-related diseases. Hepcidin is a key
      regulator of iron homeostasis whose expression changes are often indicative of
      abnormal iron metabolism. There are few reports of hepcidin levels in patients
      with HBV infections, and the available results are inconsistent. In this study,
      using a recently validated nanopore silica film based method, we measured serum
      hepcidin levels in 46 HBV-related patients and 20 healthy controls. Patients were
      divided into three groups: chronic hepatitis B without cirrhosis; HBV-related
      cirrhosis; and HBV-related cirrhosis with hepatocellular carcinoma. Compared to
      healthy controls, the mean serum hepcidin level was significantly higher in CHB
      patients without cirrhosis, and in those with hepatocellular carcinoma, but not
      in those with cirrhosis. Iron-loading, viral infection and liver dysfunction are
      determined to be the major regulators of hepcidin in these patients. These
      observations suggest correlations between serum hepcidin and progression of
      chronic HBV infection, and may shed a new light on the development of biomarkers
      for HBV-related disease surveillance.

PMID- 27694816
TI  - Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin
      mutants.
AB  - Retinitis pigmentosa (RP) is a blinding disease often associated with mutations
      in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid
      scramblase. Most RP-associated mutations affect rhodopsin's activity or transport
      to disc membranes. Intriguingly, some mutations produce apparently normal
      rhodopsins that nevertheless cause disease. Here we show that three such
      enigmatic mutations-F45L, V209M and F220C-yield fully functional visual pigments
      that bind the 11-cis retinal chromophore, activate the G protein transducin,
      traffic to the light-sensitive photoreceptor compartment and scramble
      phospholipids. However, tests of scramblase activity show that unlike wild-type
      rhodopsin that functionally reconstitutes into liposomes as dimers or multimers,
      F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in
      pull-down experiments. Our data suggest that the photoreceptor pathology
      associated with expression of these enigmatic RP-associated pigments arises from
      their unexpected inability to dimerize via transmembrane helices 1 and 5.

PMID- 27694817
TI  - Efficient long-term cryopreservation of pluripotent stem cells at -80  degrees C.
AB  - Current long term cryopreservation of cell stocks routinely requires the use of
      liquid nitrogen (LN2), because commonly used cryopreservation media containing
      cell membrane permeating cryoprotectants are thermally unstable when frozen at
      higher storage temperatures, e.g. -80  degrees C. This instability leads to ice
      recrystallization, causing progressive loss of cell viability over time under the
      storage conditions provided by most laboratory deep freezers. The dependency on
      LN2 for cell storage significantly increases operational expense and raises
      issues related to impaired working efficiency and safety. Here we demonstrate
      that addition of Ficoll 70 to cryoprotectant solutions significantly improves
      system thermal stability at the working temperature (~-80  degrees C) of
      laboratory deep freezers. Moreover, a medium comprised of Ficoll 70 and dimethyl
      sulfoxide (DMSO) in presence or absence of fetal bovine serum (FBS) can provide
      reliable cryopreservation of various kinds of human and porcine pluripotent stem
      cells at -80  degrees C for periods that extend up to at least one year, with the
      post-thaw viability, plating efficiency, and full retention of pluripotent
      phenotype comparable to that achieved with LN2 storage. These results illustrate
      the practicability of a promising long-term cryopreservation method that
      completely eliminates the need for LN2.

PMID- 27694819
TI  - Pollen-mediated gene flow and seed exchange in small-scale Zambian maize farming,
      implications for biosafety assessment.
AB  - Gene flow in agricultural crops is important for risk assessment of genetically
      modified (GM) crops, particularly in countries with a large informal agricultural
      sector of subsistence cultivation. We present a pollen flow model for maize (Zea
      mays), a major staple crop in Africa. We use spatial properties of fields (size,
      position) in three small-scale maize farming communities in Zambia and estimate
      rates of cross-fertilisation between fields sown with different maize varieties
      (e.g. conventional and transgene). As an additional factor contributing to gene
      flow, we present data on seed saving and sharing among farmers that live in the
      same communities. Our results show that: i) maize fields were small and located
      in immediate vicinity of neighboring fields; ii) a majority of farmers saved and
      shared seed; iii) modeled rates of pollen-mediated gene flow showed extensive
      mixing of germplasm between fields and farms and iv) as a result, segregation of
      GM and non-GM varieties is not likely to be an option in these systems. We
      conclude that the overall genetic composition of maize, in this and similar
      agricultural contexts, will be strongly influenced both by self-organised
      ecological factors (pollen flow), and by socially mediated intervention (seed
      recycling and sharing).

PMID- 27694818
TI  - Reduced lipolysis response to adipose afferent reflex involved in impaired
      activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity.
AB  - Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex
      (AAR) and sympathetic activation. This study is to investigate the effects of AAR
      on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR
      in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was
      induced by injection of capsaicin into inguinal WAT or electrical stimulation of
      epididymal WAT afferent nerve. AAR caused sympathetic activation, which was
      enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted
      hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased
      lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP,
      perilipin and beta-adrenoceptor levels were reduced, while HSL was upregulated in
      adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP
      levels and PKA activity, promoted HSL and perilipin phosphorylation, and
      increased lipolysis, which were attenuated in obesity rats. The attenuated
      effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP
      analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced
      AAR in obesity is attributed to the impaired activation of beta-adrenoceptor-cAMP
      PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated
      lipolysis in obesity.

PMID- 27694820
TI  - A novel method for preparing microplastic fibers.
AB  - Microscopic plastic (microplastic, 0.1 um-5 mm) is a widespread pollutant
      impacting upon aquatic ecosystems across the globe. Environmental sampling has
      revealed synthetic fibers are prevalent in seawater, sediments and biota.
      However, microplastic fibers are rarely used in laboratory studies as they are
      unavailable for purchase and existing preparation techniques have limited
      application. To facilitate the incorporation of environmentally relevant
      microplastic fibers into future studies, new methods are required. Here, a novel
      cryotome protocol has been developed. Nylon, polyethylene terephthalate and
      polypropylene fibers (10-28 MUm diameter) were aligned, embedded in water-soluble
      freezing agent, and sectioned (40-100 MUm length) using a cryogenic microtome.
      Microplastic fibers were prepared to specified lengths (P < 0.05, ANOVA) and
      proved consistent in size. Fluorescent labelling of Nylon microfibers with Nile
      Red facilitated imaging. A 24 h feeding experiment confirmed bioavailability of
      10 * 40 MUm Nylon fibers to brine shrimp (Artemia sp). This protocol provides a
      consistent method for preparing standardised fibrous microplastics, with widths
      similar to those observed in the natural environment, which could ultimately lead
      to a better understanding of the biological and ecological effects of
      microplastic debris in the environment.

PMID- 27694821
TI  - Erratum: Global phylogeography and evolutionary history of Shigella dysenteriae
      type 1.

PMID- 27694823
TI  - Coral recovery in the central Maldives archipelago since the last major mass
      bleaching, in 1998.
AB  - Increasing frequency and severity of disturbances is causing global degradation
      of coral reef ecosystems. This study examined temporal changes in live coral
      cover and coral composition in the central Maldives from 1997 to 2016,
      encompassing two bleaching events, a tsunami, and an outbreak of Acanthaster
      planci. We also examined the contemporary size structure for five dominant coral
      taxa (tabular Acropora, Acropora muricata, Acropora humilis, Pocillopora spp, and
      massive Porites). Total coral cover increased throughout the study period, with
      marked increases following the 1998 mass-bleaching. The relative abundance of key
      genera has changed through time, where Acropora and Pocillopora (which are highly
      susceptible to bleaching) were under-represented following 1998 mass-bleaching
      but increased until outbreaks of A. planci in 2015. The contemporary size
      structure for all coral taxa was dominated by larger colonies with peaked
      distributions suggesting that recent disturbances had a disproportionate impact
      on smaller colonies, or that recruitment is currently limited. This may suggest
      that coral resilience has been compromised by recent disturbances, and further
      bleaching (expected in 2016) could lead to highly protracted recovery times. We
      showed that Maldivian reefs recovered following the 1998 mass-bleaching event,
      but it took up to a decade, and ongoing disturbances may be eroding reef
      resilience.

PMID- 27694822
TI  - A sensitive electrochemical sensor for in vitro detection of parathyroid hormone
      based on a MoS2-graphene composite.
AB  - This paper reports a biosensor based on a MoS2-graphene (MG) composite that can
      measure the parathyroid hormone (PTH) concentration in serum samples from
      patients. The interaction between PTH and MG was analysed via an electrochemical
      sensing technique. The MG was functionalized using l-cysteine. Following this,
      PTH could be covalently immobilized on the MG sensing electrode. The properties
      of MG were evaluated using scanning electron microscopy, high-resolution
      transmission electron microscopy, X-ray diffraction, Raman spectroscopy, X-ray
      photoelectron spectroscopy, and Fourier transform infrared spectrometry.
      Following optimization of immobilized materials-such as MG, PTH, and alkaline
      phosphatase (ALP)-the performance of the MG sensor was investigated via cyclic
      voltammetry, to assess its linearity, repeatability, and reproducibility.
      Electrochemical impedance spectroscopy was performed on graphene oxide (GO) and
      MG-modified electrodes to confirm the capture of a monoclonal antibody (MAb)
      targeting PTH. Furthermore, the ALP-PTH-MG sensor exhibits a linear response
      towards PTH from artificial serum over a range of 1-50 pg mL-1. Moreover, patient
      sera (n = 30) were evaluated using the ALP-PTH-MG sensor and compared using
      standard equipment (Roche E 170). The P-value is less than 0.01 when evaluated
      with a t-test using Welch's correction. This implies that the fabricated sensor
      can be deployed for medical diagnosis.

PMID- 27694824
TI  - A Statistical Learning Framework for Materials Science: Application to Elastic
      Moduli of k-nary Inorganic Polycrystalline Compounds.
AB  - Materials scientists increasingly employ machine or statistical learning (SL)
      techniques to accelerate materials discovery and design. Such pursuits benefit
      from pooling training data across, and thus being able to generalize predictions
      over, k-nary compounds of diverse chemistries and structures. This work presents
      a SL framework that addresses challenges in materials science applications, where
      datasets are diverse but of modest size, and extreme values are often of
      interest. Our advances include the application of power or Holder means to
      construct descriptors that generalize over chemistry and crystal structure, and
      the incorporation of multivariate local regression within a gradient boosting
      framework. The approach is demonstrated by developing SL models to predict bulk
      and shear moduli (K and G, respectively) for polycrystalline inorganic compounds,
      using 1,940 compounds from a growing database of calculated elastic moduli for
      metals, semiconductors and insulators. The usefulness of the models is
      illustrated by screening for superhard materials.

PMID- 27694825
TI  - Tracing ancestor rice of Suriname Maroons back to its African origin.
AB  - African rice (Oryza glaberrima) and African cultivation practices are said to
      have influenced emerging colonial plantation economies in the Americas1,2.
      However, the level of impact of African rice practices is difficult to establish
      because of limited written or botanical records2,3. Recent findings of O.
      glaberrima in rice fields of Suriname Maroons bear evidence of the high level of
      knowledge about rice among African slaves and their descendants, who consecrate
      it in ancestor rituals4,5. Here we establish the strong similarity, and hence
      likely origin, of the first extant New World landrace of O. glaberrima to
      landraces from the Upper Guinean forests in West Africa. We collected African
      rice from a Maroon market in Paramaribo, Suriname, propagated it, sequenced its
      genome6 and compared it with genomes of 109 accessions representing O. glaberrima
      diversity across West Africa. By analysing 1,649,769 single nucleotide
      polymorphisms (SNPs) in clustering analyses, the Suriname sample appears sister
      to an Ivory Coast landrace, and shows no evidence of introgression from Asian
      rice. Whereas the Dutch took most slaves from Ghana, Benin and Central Africa7,
      the diaries of slave ship captains record the purchase of food for provisions
      when sailing along the West African Coast8, offering one possible explanation for
      the patterns of genetic similarity. This study demonstrates the utility of
      genomics in understanding the largely unwritten histories of crop cultures of
      diaspora communities.

PMID- 27694826
TI  - Hydrodynamic role of longitudinal dorsal ridges in a leatherback turtle swimming.
AB  - Leatherback sea turtles (Dermochelys coriacea) are known to have a superior
      diving ability and be highly adapted to pelagic swimming. They have five
      longitudinal ridges on their carapace. Although it was conjectured that these
      ridges might be an adaptation for flow control, no rigorous study has been
      performed to understand their hydrodynamic roles. Here we show that these ridges
      are slightly misaligned to the streamlines around the body to generate streamwise
      vortices, and suppress or delay flow separation on the carapace, resulting in
      enhanced hydrodynamic performances during different modes of swimming. Our
      results suggest that shapes of some morphological features of living creatures,
      like the longitudinal ridges of the leatherback turtles, need not be streamlined
      for excellent hydro- or aerodynamic performances, contrary to our common physical
      intuition.

PMID- 27694827
TI  - Chemical chaperone TUDCA prevents apoptosis and improves survival during
      polymicrobial sepsis in mice.
AB  - Sepsis-induced lymphopenia is a major cause of morbidities in intensive care
      units and in populations with chronic conditions such as renal failure, diabetes,
      HIV and alcohol abuse. Currently, other than supportive care and antibiotics,
      there are no treatments for this condition. We developed an in vitro assay to
      understand the role of the ER-stress-mediated apoptosis process in lymphocyte
      death during polymicrobial sepsis, which was reproducible in in vivo mouse
      models. Modulating ER stress using chemical chaperones significantly reduced the
      induction of the pro-apoptotic protein Bim both in vitro and in mice.
      Furthermore, in a 'two-hit' pneumonia model in mice, we have been able to
      demonstrate that administration of the chemical chaperone TUDCA helped to
      maintain lymphocyte homeostasis by significantly reducing lymphocyte apoptosis
      and this correlated with four-fold improvement in survival. Our results
      demonstrate a novel therapeutic opportunity for treating sepsis-induced
      lymphopenia in humans.

PMID- 27694829
TI  - Systemic Inhibition of CREB is Well-tolerated in vivo.
AB  - cAMP-response element binding protein (CREB) is a nuclear transcription factor
      activated by multiple extracellular signals including growth factors and
      hormones. These extracellular cues activate CREB through phosphorylation at
      Ser133 by various protein serine/threonine kinases. Once phosphorylated, it
      promotes its association with transcription coactivators CREB-binding protein
      (CBP) and its paralog p300 to activate CREB-dependent gene transcription. Tumor
      tissues of different origins have been shown to present overexpression and/or
      overactivation of CREB, indicating CREB as a potential cancer drug target. We
      previously identified 666-15 as a potent inhibitor of CREB with efficacious anti
      cancer activity both in vitro and in vivo. Herein, we investigated the
      specificity of 666-15 and evaluated its potential in vivo toxicity. We found that
      666-15 was fairly selective in inhibiting CREB. 666-15 was also found to be
      readily bioavailable to achieve pharmacologically relevant concentrations for
      CREB inhibition. Furthermore, the mice treated with 666-15 showed no evidence of
      changes in body weight, complete blood count, blood chemistry profile, cardiac
      contractility and tissue histologies from liver, kidney and heart. For the first
      time, these results demonstrate that pharmacological inhibition of CREB is well
      tolerated in vivo and indicate that such inhibitors should be promising cancer
      therapeutics.

PMID- 27694830
TI  - Noise reduction facilitated by dosage compensation in gene networks.
AB  - Genetic noise together with genome duplication and volume changes during cell
      cycle are significant contributors to cell-to-cell heterogeneity. How can cells
      buffer the effects of these unavoidable epigenetic and genetic variations on
      phenotypes that are sensitive to such variations? Here we show that a simple
      network motif that is essential for network-dosage compensation can reduce the
      effects of extrinsic noise on the network output. Using natural and synthetic
      gene networks with and without the network motif, we measure gene network
      activity in single yeast cells and find that the activity of the compensated
      network is significantly lower in noise compared with the non-compensated
      network. A mathematical analysis provides intuitive insights into these results
      and a novel stochastic model tracking cell-volume and cell-cycle predicts the
      experimental results. Our work implies that noise is a selectable trait tunable
      by evolution.

PMID- 27694828
TI  - Comprehensive functional analysis of the tousled-like kinase 2 frequently
      amplified in aggressive luminal breast cancers.
AB  - More aggressive and therapy-resistant oestrogen receptor (ER)-positive breast
      cancers remain a great clinical challenge. Here our integrative genomic analysis
      identifies tousled-like kinase 2 (TLK2) as a candidate kinase target frequently
      amplified in ~10.5% of ER-positive breast tumours. The resulting overexpression
      of TLK2 is more significant in aggressive and advanced tumours, and correlates
      with worse clinical outcome regardless of endocrine therapy. Ectopic expression
      of TLK2 leads to enhanced aggressiveness in breast cancer cells, which may
      involve the EGFR/SRC/FAK signalling. Conversely, TLK2 inhibition selectively
      inhibits the growth of TLK2-high breast cancer cells, downregulates ERalpha, BCL2
      and SKP2, impairs G1/S cell cycle progression, induces apoptosis and
      significantly improves progression-free survival in vivo. We identify two
      potential TLK2 inhibitors that could serve as backbones for future drug
      development. Together, amplification of the cell cycle kinase TLK2 presents an
      attractive genomic target for aggressive ER-positive breast cancers.

PMID- 27694831
TI  - RAB39B gene mutations are not linked to familial Parkinson's disease in China.
AB  - Recently, RAB39B mutations were reported to be a causative factor in patients
      with Parkinson's disease (PD). To validate the role of RAB39B in familial PD, a
      total of 195 subjects consisting of 108 PD families with autosomal-dominant (AD)
      inheritance and 87 PD families with autosomal-recessive (AR) inheritance in the
      Chinese Han population from mainland China were included in this study. We did
      not identify any variants in the coding region or the exon-intron boundaries of
      the gene by Sanger sequencing method in the DNA samples of 180 patients (100 with
      AD and 80 with AR). Furthermore, we did not find any variants in the RAB39B gene
      when Whole-exome sequencing (WES) was applied to DNA samples from 15 patients (8
      with AD and 7 with AR) for further genetic analysis. Additionally, when
      quantitative real-time PCR was used to exclude large rearrangement variants in
      these patients, we found no dosage mutations in RAB39B gene. Our results suggest
      that RAB39B mutation is very rare in familial PD and may not be a major cause of
      familial PD in the Chinese Han Population.

PMID- 27694832
TI  - Quantifying the dilution of the radiocesium contamination in Fukushima coastal
      river sediment (2011-2015).
AB  - Fallout from the Fukushima Dai-ichi nuclear power plant accident resulted in a
      3000-km2 radioactive contamination plume. Here, we model the progressive dilution
      of the radiocesium contamination in 327 sediment samples from two neighboring
      catchments with different timing of soil decontamination. Overall, we demonstrate
      that there has been a ~90% decrease of the contribution of upstream contaminated
      soils to sediment transiting the coastal plains between 2012 (median - M -
      contribution of 73%, mean absolute deviation - MAD - of 27%) and 2015 (M 9%, MAD
      6%). The occurrence of typhoons and the progress of decontamination in different
      tributaries of the Niida River resulted in temporary increases in local
      contamination. However, the much lower contribution of upstream contaminated
      soils to coastal plain sediment in November 2015 demonstrates that the source of
      the easily erodible, contaminated material has potentially been removed by
      decontamination, diluted by subsoils, or eroded and transported to the Pacific
      Ocean.

PMID- 27694833
TI  - A 17 GHz molecular rectifier.
AB  - Molecular electronics originally proposed that small molecules sandwiched between
      electrodes would accomplish electronic functions and enable ultimate scaling to
      be reached. However, so far, functional molecular devices have only been
      demonstrated at low frequency. Here, we demonstrate molecular diodes operating up
      to 17.8 GHz. Direct current and radio frequency (RF) properties were
      simultaneously measured on a large array of molecular junctions composed of gold
      nanocrystal electrodes, ferrocenyl undecanethiol molecules and the tip of an
      interferometric scanning microwave microscope. The present nanometre-scale
      molecular diodes offer a current density increase by several orders of magnitude
      compared with that of micrometre-scale molecular diodes, allowing RF operation.
      The measured S11 parameters show a diode rectification ratio of 12 dB which is
      linked to the rectification behaviour of the direct current conductance. From the
      RF measurements, we extrapolate a cut-off frequency of 520 GHz. A comparison with
      the silicon RF-Schottky diodes, architecture suggests that the RF-molecular
      diodes are extremely attractive for scaling and high-frequency operation.

PMID- 27694835
TI  - The interplay between HPIP and casein kinase 1alpha promotes renal cell carcinoma
      growth and metastasis via activation of mTOR pathway.
AB  - Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein
      (HPIP) was shown to be crucial during the development and progression of a
      variety of tumors. However, the role of HPIP in renal cell carcinoma (RCC) is
      unknown. Here we report that HPIP is upregulated in most RCC patients, positively
      correlates with tumor size, high Fuhrman grade and preoperative metastasis, and
      predicts poor clinical outcomes. Mechanistically, we identified casein kinase
      1alpha (CK1alpha), a critical regulator of tumorigenesis and metastasis, as a
      novel HPIP-interacting protein. HPIP facilitates RCC cell growth, migration,
      invasion and epithelial-mesenchymal transition depending on its interaction with
      CK1alpha. Activation of mammalian target of rapamycin pathways by HPIP is partly
      dependent on CK1alpha and is required for HPIP modulation of RCC cell
      proliferation and migration. HPIP knockdown suppresses renal tumor growth and
      metastasis in nude mice through CK1alpha. Moreover, expression of CK1alpha is
      positively correlated with HPIP in RCC samples, and also predicts poor clinical
      outcome-like expression of HPIP. Taken together, our data demonstrate the
      critical regulatory role of the HPIP-CK1alpha interaction in RCC, and suggest
      that HPIP and CK1alpha may be potential targets for RCC therapy.

PMID- 27694834
TI  - DUOX1 silencing in lung cancer promotes EMT, cancer stem cell characteristics and
      invasive properties.
AB  - Dual oxidase 1 (DUOX1) is an oxidant-generating enzyme within the airway
      epithelium that participates in innate airway host defense and epithelial
      homeostasis. Recent studies indicate that DUOX1 is suppressed in lung cancers by
      epigenetic silencing, although the importance of DUOX1 silencing in lung cancer
      development or progression is unknown. Here we show that loss of DUOX1 expression
      in a panel of lung cancer cell lines is strongly associated with loss of the
      epithelial marker E-cadherin. Moreover, RNAi-mediated DUOX1 silencing in lung
      epithelial cells and the cancer cell line NCI-H292 was found to result in loss of
      epithelial characteristics/molecular features (altered morphology, reduced
      barrier function and loss of E-cadherin) and increased mesenchymal features
      (increased migration, anchorage-independent growth and gain of
      vimentin/collagen), suggesting a direct contribution of DUOX1 silencing to
      epithelial-to-mesenchymal transition (EMT), an important feature of metastatic
      cancer. Conversely, overexpression of DUOX1 in A549 cells was capable of
      reversing EMT features. DUOX1 silencing in H292 cells also led to enhanced
      resistance to epidermal growth factor receptor tyrosine kinase inhibitors such as
      erlotinib, and enhanced levels of cancer stem cell (CSC) markers CD133 and ALDH1.
      Furthermore, acquired resistance of H292 cells to erlotinib resulted in enhanced
      EMT and CSC features, as well as loss of DUOX1. Finally, compared with control
      H292 cells, H292-shDUOX1 cells displayed enhanced invasive features in vitro and
      in vivo. Collectively, our findings indicate that DUOX1 silencing in lung
      epithelial cancer cells promotes features of EMT, and may be strongly associated
      with invasive and metastatic lung cancer.

PMID- 27694837
TI  - Corrigendum: The abundant marine bacterium Pelagibacter simultaneously
      catabolizes dimethylsulfoniopropionate to the gases dimethyl sulfide and
      methanethiol.

PMID- 27694836
TI  - The Zn-finger domain of MdmX suppresses cancer progression by promoting genome
      stability in p53-mutant cells.
AB  - The MDMX (MDM4) oncogene is amplified or overexpressed in a significant
      percentage of human tumors. MDMX is thought to function as an oncoprotein by
      binding p53 tumor suppressor protein to inhibit p53-mediated transcription, and
      by complexing with MDM2 oncoprotein to promote MDM2-mediated degradation of p53.
      However, down-regulation or loss of functional MDMX has also been observed in a
      variety of human tumors that are mutated for p53, often correlating with more
      aggressive cancers and a worse patient prognosis. We have previously reported
      that endogenous levels of MdmX can suppress proliferation and promote pseudo
      bipolar mitosis in primary and tumor cells derived from p53-deficient mice, and
      that MdmX-p53 double deficient mice succumb to spontaneously formed tumors more
      rapidly than p53-deficient mice. These results suggest that the MdmX oncoprotein
      may act as a tumor-suppressor in cancers with compromised p53 function. By using
      orthotopic transplantation and lung colonization assays in mice we now establish
      a p53-independent anti-oncogenic role for MdmX in tumor progression. We also
      demonstrate that the roles of MdmX in genome stability and in proliferation are
      two distinct functions encoded by the separate MdmX protein domains. The central
      Zn-finger domain suppresses multipolar mitosis and chromosome loss, whereas the
      carboxy-terminal RING domain suppresses proliferation of p53-deficient cells.
      Furthermore, we determine that it is the maintenance of genome stability that
      underlies MdmX role in suppression of tumorigenesis in hyperploid p53 mutant
      tumors. Our results offer a rationale for the increased metastatic potential of
      p53 mutant human cancers with aberrant MdmX function and provide a caveat for the
      application of anti-MdmX treatment of tumors with compromised p53 activity.

PMID- 27694839
TI  - Investigating enhanced mechanical properties in dual-phase Fe-Ga-Tb alloys.
AB  - Dual-phase (Fe83Ga17)100-xTbx alloys with 0 <= x <= 1 were synthesized by arc
      melting and homogenization treatment. The microstructures and the corresponding
      mechanical properties were systematically investigated. The chemical composition
      of the body centered cubic matrix is Fe83Ga17. The monoclinic second phase was
      composed of meltable precipitates with approximate composition Fe57Ga33Tb10. The
      nano-hardness of matrix and precipitates were 2.55 +/- 0.17 GPa and 6.81 +/- 1.03
      GPa, respectively. Both the ultimate tensile strength (UTS) and fracture strain
      (epsilon) of the alloys were improved by the precipitates for x <= 0.2 alloys,
      but the strain decreases significantly at higher values of x. As potential
      structural-functional materials, the best mechanical properties obtained were a
      UTS of 595 +/- 10 MPa and an epsilon of 3.5 +/- 0.1%, four-fold and seven-fold
      improvements compared with the un-doped alloy. The mechanism for these anomalous
      changes of mechanical properties was attributed to the dispersed precipitates and
      semi-coherent interfaces, which serve as strong obstacles to dislocation motion
      and reduce the stress concentration at the grain boundaries. A sizeable
      improvement of magnetostriction induced by the precipitates in the range 0 <= x
      <= 0.2 was discovered and an optimal value of 150 +/- 5 ppm is found, over three
      times higher than that of the un-doped alloy.

PMID- 27694838
TI  - A vector platform for the rapid and efficient engineering of stable complex
      transgenes.
AB  - We describe the generation of a set of plasmid vector tools that allow the rapid
      generation of complex-interacting stable transgenes in immortalized and primary
      cells. Of particular importance is inclusion of a mechanism to monitor the
      activation status of regulatory pathways via a reporter cassette (using Gaussia
      Luciferase), with control of additional transgene expression through doxycycline
      de-repression. The resulting vectors can be used to assess regulatory pathway
      activation and are well suited for regulatory pathway crosstalk studies. The
      system incorporates MultiSite-Gateway cloning for the rapid generation of vectors
      allowing flexible choice of promoters and transgenes, and Sleeping Beauty
      transposase technology for efficient incorporation of multiple transgenes in into
      host cell DNA. The vectors and a library of compatible Gateway Entry clones are
      available from the non-profit plasmid repository Addgene.

PMID- 27694840
TI  - Insertion of an Alu element in a lncRNA leads to primate-specific modulation of
      alternative splicing.
AB  - Noncoding RNAs, mobile elements, and alternative splicing are all critical for
      the regulation of gene expression. Here we show that a conserved noncoding RNA
      acquires a new function due to the insertion of a mobile element. We identified a
      noncoding RNA, termed 5S-OT, which is transcribed from 5S rDNA loci in eukaryotes
      including fission yeast and mammals. 5S-OT plays a cis role in regulating the
      transcription of 5S rRNA in mice and humans. In the anthropoidea suborder of
      primates, an antisense Alu element has been inserted at the 5S-OT locus. We found
      that in human cells, 5S-OT regulates alternative splicing of multiple genes in
      trans via Alu/anti-Alu pairing with target genes and by interacting with the
      splicing factor U2AF65. This trans effect of 5S-OT in splicing might be exploited
      in biotechnological applications.

PMID- 27694841
TI  - Structure of the active form of Dcp1-Dcp2 decapping enzyme bound to m7GDP and its
      Edc3 activator.
AB  - Elimination of the 5' cap of eukaryotic mRNAs, known as decapping, is considered
      to be a crucial, irreversible and highly regulated step required for the rapid
      degradation of mRNA by Xrn1, the major cytoplasmic 5'-3' exonuclease. Decapping
      is accomplished by the recruitment of a protein complex formed by the Dcp2
      catalytic subunit and its Dcp1 cofactor. However, this complex has a low
      intrinsic enzymatic activity and requires several accessory proteins such as the
      Lsm1-7 complex, Pat1, Edc1-Edc2 and/or Edc3 to be fully active. Here we present
      the crystal structure of the active form of the yeast Kluyveromyces lactis Dcp1
      Dcp2 enzyme bound to its product (m7GDP) and its potent activator Edc3. This
      structure of the Dcp1-Dcp2 complex bound to a cap analog further explains
      previously published data on substrate binding and provides hints as to the
      mechanism of Edc3-mediated Dcp2 activation.

PMID- 27694842
TI  - Structural basis of mRNA-cap recognition by Dcp1-Dcp2.
AB  - Removal of the 5' cap on mRNA by the decapping enzyme Dcp2 is a critical step in
      5'-to-3' mRNA decay. Understanding the structural basis of Dcp2 activity has been
      a challenge because Dcp2 is dynamic and has weak affinity for the cap substrate.
      Here we present a 2.6-A-resolution crystal structure of a heterotrimer of fission
      yeast Dcp2, its essential activator Dcp1, and the human NMD cofactor PNRC2, in
      complex with a tight-binding cap analog. Cap binding is accompanied by a
      conformational change in Dcp2, thereby forming a composite nucleotide-binding
      site comprising conserved residues in the catalytic and regulatory domains.
      Kinetic analysis of PNRC2 revealed that a conserved short linear motif enhances
      both substrate affinity and the catalytic step of decapping. These findings
      explain why Dcp2 requires a conformational change for efficient catalysis and
      reveals that coactivators promote RNA binding and the catalytic step of
      decapping, possibly through different conformational states.

PMID- 27694843
TI  - The Growth Pattern of Tibetan Infants at High Altitudes: a Cohort Study in Rural
      Tibet region.
AB  - Studies on growth pattern of Tibetan infants and the difference from other child
      groups were limited due to its special living environment and unique customs. In
      this study, 253 Tibetan infants were followed-up from their birth to 12th month
      in rural Tibet. Five visits were conducted and weight and length were measured at
      each visit. Mixed model was employed to analyze the growth pattern of Tibetan
      infants and its comparison to the Han infants. Propensity Scores (PS) technique
      was adopted to control for the potential confounding factors. The mixed model
      found that the birth weight/length had a negative impact on the increment of
      Tibetan infants after birth (weight: beta = -0.6819, P < 0.0001, length: beta = 
      0.9571, P < 0.0001). The weight increment of Tibetan infants was greater than Han
      infant with age (betaage*ethnic = 0.0345, P < 0.001), after using PS as a
      covariant. And another mixed model in which PS was used as a matching factor
      found similar trend. Compared with Chinese Han infants, Tibetan infants were
      lower weight and shorter length within one year after birth but they had greater
      increment of weight, suggesting that Tibetan infants might have a significant
      catch-up growth within the first year of life.

PMID- 27694844
TI  - An Adaptive Fisher's Combination Method for Joint Analysis of Multiple Phenotypes
      in Association Studies.
AB  - Currently, the analyses of most genome-wide association studies (GWAS) have been
      performed on a single phenotype. There is increasing evidence showing that
      pleiotropy is a widespread phenomenon in complex diseases. Therefore, using only
      one single phenotype may lose statistical power to identify the underlying
      genetic mechanism. There is an increasing need to develop and apply powerful
      statistical tests to detect association between multiple phenotypes and a genetic
      variant. In this paper, we develop an Adaptive Fisher's Combination (AFC) method
      for joint analysis of multiple phenotypes in association studies. The AFC method
      combines p-values obtained in standard univariate GWAS by using the optimal
      number of p-values which is determined by the data. We perform extensive
      simulations to evaluate the performance of the AFC method and compare the power
      of our method with the powers of TATES, Tippett's method, Fisher's combination
      test, MANOVA, MultiPhen, and SUMSCORE. Our simulation studies show that the
      proposed method has correct type I error rates and is either the most powerful
      test or comparable with the most powerful test. Finally, we illustrate our
      proposed methodology by analyzing whole-genome genotyping data from a lung
      function study.

PMID- 27694845
TI  - Methyl-CpG binding domain protein acts to regulate the repair of cyclobutane
      pyrimidine dimers on rice DNA.
AB  - UVB radiation causes cyclobutane pyrimidine dimers (CPDs) to form on the DNA of
      living organisms. This study found that overexpression of the silicon absorbance
      gene Lsi1 reduced the accumulation of CPDs in rice, which profited from the
      reactivation by photolyase. The transcript abundance of deoxyribodipyrimidine
      photolyase (Os10g0167600) was generally correlated with the silicon content of
      the rice, and the up-regulation of Os10g0167600 was found to be highest in the
      UVB-treated Lsi1-overexpressed (Lsi1-OX) rice. A trans-acting factor, methyl-CpG
      binding domain protein (OsMeCP), was found to interact with the cis-element of
      Os10g0167600. The nucleic location of OsMeCP effectively enabled the
      transcriptional regulation. Compared with the WT, the level of OsMeCP was lower
      in the Lsi1-OX rice but higher in the Lsi1-RNAi line. Rice cultured in a high
      silicate-concentration solution also exhibited less OsMeCP abundance.
      Overexpression of OsMeCP led to lower Os10g0167600 transcript levels and a higher
      CPD content than in the WT, but the reverse was true in the OsMeCP-RNAi line.
      These findings indicate that OsMeCP acts as a negative regulator of silicon, and
      can mediate the repression of the transcription from Os10g0167600, which inhibits
      the photoreactivation of the photolyase involved in the repair of CPDs.

PMID- 27694848
TI  - Self-assembly: Materials from a peptide soup.

PMID- 27694847
TI  - Notch filtering the nuclear environment of a spin qubit.
AB  - Electron spins in gate-defined quantum dots provide a promising platform for
      quantum computation. In particular, spin-based quantum computing in gallium
      arsenide takes advantage of the high quality of semiconducting materials,
      reliability in fabricating arrays of quantum dots and accurate qubit operations.
      However, the effective magnetic noise arising from the hyperfine interaction with
      uncontrolled nuclear spins in the host lattice constitutes a major source of
      decoherence. Low-frequency nuclear noise, responsible for fast (10 ns)
      inhomogeneous dephasing, can be removed by echo techniques. High-frequency
      nuclear noise, recently studied via echo revivals, occurs in narrow-frequency
      bands related to differences in Larmor precession of the three isotopes 69Ga,
      71Ga and 75As (refs 15,16,17). Here, we show that both low- and high-frequency
      nuclear noise can be filtered by appropriate dynamical decoupling sequences,
      resulting in a substantial enhancement of spin qubit coherence times. Using
      nuclear notch filtering, we demonstrate a spin coherence time (T2) of 0.87 ms,
      five orders of magnitude longer than typical exchange gate times, and exceeding
      the longest coherence times reported to date in Si/SiGe gate-defined quantum
      dots.

PMID- 27694846
TI  - EIN2-dependent regulation of acetylation of histone H3K14 and non-canonical
      histone H3K23 in ethylene signalling.
AB  - Ethylene gas is essential for many developmental processes and stress responses
      in plants. EIN2 plays a key role in ethylene signalling but its function remains
      enigmatic. Here, we show that ethylene specifically elevates acetylation of
      histone H3K14 and the non-canonical acetylation of H3K23 in etiolated seedlings.
      The up-regulation of these two histone marks positively correlates with ethylene
      regulated transcription activation, and the elevation requires EIN2. Both EIN2
      and EIN3 interact with a SANT domain protein named EIN2 nuclear associated
      protein 1 (ENAP1), overexpression of which results in elevation of histone
      acetylation and enhanced ethylene-inducible gene expression in an EIN2-dependent
      manner. On the basis of these findings we propose a model where, in the presence
      of ethylene, the EIN2 C terminus contributes to downstream signalling via the
      elevation of acetylation at H3K14 and H3K23. ENAP1 may potentially mediate
      ethylene-induced histone acetylation via its interactions with EIN2 C terminus.

PMID- 27694849
TI  - Nanoscale topographical control of capillary assembly of nanoparticles.
AB  - Predetermined and selective placement of nanoparticles onto large-area substrates
      with nanometre-scale precision is essential to harness the unique properties of
      nanoparticle assemblies, in particular for functional optical and electro-optical
      nanodevices. Unfortunately, such high spatial organization is currently beyond
      the reach of top-down nanofabrication techniques alone. Here, we demonstrate that
      topographic features comprising lithographed funnelled traps and auxiliary
      sidewalls on a solid substrate can deterministically direct the capillary
      assembly of Au nanorods to attain simultaneous control of position, orientation
      and interparticle distance at the nanometre level. We report up to 100% assembly
      yield over centimetre-scale substrates. We achieve this by optimizing the three
      sequential stages of capillary nanoparticle assembly: insertion of nanorods into
      the traps, resilience against the receding suspension front and drying of the
      residual solvent. Finally, using electron energy-loss spectroscopy we
      characterize the spectral response and near-field properties of spatially
      programmable Au nanorod dimers, highlighting the opportunities for precise
      tunability of the plasmonic modes in larger assemblies.

PMID- 27694850
TI  - Dynamic peptide libraries for the discovery of supramolecular nanomaterials.
AB  - Sequence-specific polymers, such as oligonucleotides and peptides, can be used as
      building blocks for functional supramolecular nanomaterials. The design and
      selection of suitable self-assembling sequences is, however, challenging because
      of the vast combinatorial space available. Here we report a methodology that
      allows the peptide sequence space to be searched for self-assembling structures.
      In this approach, unprotected homo- and heterodipeptides (including aromatic,
      aliphatic, polar and charged amino acids) are subjected to continuous enzymatic
      condensation, hydrolysis and sequence exchange to create a dynamic combinatorial
      peptide library. The free-energy change associated with the assembly process
      itself gives rise to selective amplification of self-assembling candidates. By
      changing the environmental conditions during the selection process, different
      sequences and consequent nanoscale morphologies are selected.

PMID- 27694851
TI  - Site-specific identification of heparan and chondroitin sulfate
      glycosaminoglycans in hybrid proteoglycans.
AB  - Heparan sulfate (HS) and chondroitin sulfate (CS) are complex polysaccharides
      that regulate important biological pathways in virtually all metazoan organisms.
      The polysaccharides often display opposite effects on cell functions with HS and
      CS structural motifs presenting unique binding sites for specific ligands. Still,
      the mechanisms by which glycan biosynthesis generates complex HS and CS
      polysaccharides required for the regulation of mammalian physiology remain
      elusive. Here we present a glycoproteomic approach that identifies and
      differentiates between HS and CS attachment sites and provides identity to the
      core proteins. Glycopeptides were prepared from perlecan, a complex proteoglycan
      known to be substituted with both HS and CS chains, further digested with
      heparinase or chondroitinase ABC to reduce the HS and CS chain lengths
      respectively, and thereafter analyzed by nLC-MS/MS. This protocol enabled the
      identification of three consensus HS sites and one hybrid site, carrying either a
      HS or a CS chain. Inspection of the amino acid sequence at the hybrid attachment
      locus indicates that certain peptide motifs may encode for the chain type
      selection process. This analytical approach will become useful when addressing
      fundamental questions in basic biology specifically in elucidating the functional
      roles of site-specific glycosylations of proteoglycans.

PMID- 27694852
TI  - Pulled microcapillary tube resonators with electrical readout for mass sensing
      applications.
AB  - This paper reports a microfabrication-free approach to make hollow channel mass
      sensors by pulling a glass capillary and suspending it on top of a machined jig.
      A part of the pulled section makes simple contact with an actuation node and a
      quartz tuning fork (QTF) which acts as a sensing node. The two nodes define a
      pulled micro capillary tube resonator (PMUTR) simply supported at two contacts.
      While a piezo actuator beneath the actuation node excites the PMUTR, the QTF
      senses the resonance frequency of the PMUTR. The proposed concept was validated
      by electrical and optical measurements of resonant spectra of PMUTR. Then,
      different liquid samples including water, ethanol, glycerol, and their binary
      mixtures were introduced into the PMUTR and the resonance frequency of the PMUTR
      was measured as a function of liquid density. Density responsivity of -3,088 Hz-g
      1 cm3 obtained is comparable to those of microfabricated hollow resonators. With
      a micro droplet generation chip configured in series with the PMUTR, size
      distribution of oil droplets suspended in water was successfully measured with
      the radius resolution of 31 nm at the average droplet radius, 28.47 MUm. Overall,
      typical off-the-shelf parts simply constitute a resonant mass sensing system
      along with a convenient electrical readout.

PMID- 27694853
TI  - Improved affinity at the cost of decreased specificity: a recurring theme in PDZ
      peptide interactions.
AB  - The E6 protein from human papillomavirus (HPV) plays an important role during
      productive infection and is a potential drug target. We have previously designed
      a high affinity bivalent protein binder for the E6 protein, a fusion between a
      helix from the E6 associated protein and PDZO9, an engineered variant
      (L391F/K392M) of the second PDZ domain from synapse associated protein 97 (SAP97
      PDZ2). How the substitutions improve the affinity of SAP97 PDZ2 for HPV E6 is not
      clear and it is not known to what extent they affect the specificity for cellular
      targets. Here, we explore the specificity of wild type SAP97 PDZ2 and PDZO9
      through proteomic peptide phage display. In addition, we employ a double mutant
      cycle of SAP97 PDZ2 in which the binding kinetics for nine identified potential
      cellular peptide ligands are measured and compared with those for the C-terminal
      E6 peptide. The results demonstrate that PDZO9 has an increased affinity for all
      peptides, but at the cost of specificity. Furthermore, there is a peptide
      dependent coupling free energy between the side chains at positions 391 and 392.
      This corroborates our previous allosteric model for PDZ domains, involving
      sampling of intramolecular energetic pathways.

PMID- 27694854
TI  - Subcellular and in-vivo Nano-Endoscopy.
AB  - Analysis of individual cells at the subcellular level is important for
      understanding diseases and accelerating drug discovery. Nanoscale endoscopes
      allow minimally invasive probing of individual cell interiors. Several such
      instruments have been presented previously, but they are either too complex to
      fabricate or require sophisticated external detectors because of low signal
      collection efficiency. Here we present a nanoendoscope that can locally excite
      fluorescence in labelled cell organelles and collect the emitted signal for
      spectral analysis. Finite Difference Time Domain (FDTD) simulations have shown
      that with an optimized nanoendoscope taper profile, the light emission and
      collection was localized within ~100 nm. This allows signal detection to be used
      for nano-photonic sensing of the proximity of fluorophores. Upon insertion into
      the individual organelles of living cells, the nanoendoscope was fabricated and
      resultant fluorescent signals collected. This included the signal collection from
      the nucleus of Acridine orange labelled human fibroblast cells, the nucleus of
      Hoechst stained live liver cells and the mitochondria of MitoTracker Red labelled
      MDA-MB-231 cells. The endoscope was also inserted into a live organism, the
      yellow fluorescent protein producing nematode Caenorhabditis elegans, and a
      fluorescent signal was collected. To our knowledge this is the first
      demonstration of in vivo, local fluorescence signal collection on the sub
      organelle level.

PMID- 27694856
TI  - Revisit to three-dimensional percolation theory: Accurate analysis for highly
      stretchable conductive composite materials.
AB  - A percolation theory based on variation of conductive filler fraction has been
      widely used to explain the behavior of conductive composite materials under both
      small and large deformation conditions. However, it typically fails in properly
      analyzing the materials under the large deformation since the assumption may not
      be valid in such a case. Therefore, we proposed a new three-dimensional
      percolation theory by considering three key factors: nonlinear elasticity,
      precisely measured strain-dependent Poisson's ratio, and strain-dependent
      percolation threshold. Digital image correlation (DIC) method was used to
      determine actual Poisson's ratios at various strain levels, which were used to
      accurately estimate variation of conductive filler volume fraction under
      deformation. We also adopted strain-dependent percolation threshold caused by the
      filler re-location with deformation. When three key factors were considered,
      electrical performance change was accurately analyzed for composite materials
      with both isotropic and anisotropic mechanical properties.

PMID- 27694855
TI  - Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis:
      Integrating Interaction Data to Uncover Regulatory Mechanisms.
AB  - MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of
      multiple sclerosis (MS), an inflammatory disorder of the central nervous system.
      Here, we propose a new consensus-based strategy to analyse and integrate miRNA
      and gene expression data in MS as well as other publically available data to gain
      a deeper understanding of the role of miRNAs in MS and to overcome the challenges
      posed by studies with limited patient sample sizes. We processed and analysed
      microarray datasets, and compared the expression of genes and miRNAs in the blood
      of MS patients and controls. We then used our consensus and integration approach
      to construct two molecular networks dysregulated in MS: a miRNA- and a gene-based
      network. We identified 18 differentially expressed (DE) miRNAs and 128 DE genes
      that may contribute to the regulatory alterations behind MS. The miRNAs were
      linked to immunological and neurological pathways, and we exposed let-7b-5p and
      miR-345-5p as promising blood-derived disease biomarkers in MS. The results
      suggest that DE miRNAs are more informative than DE genes in uncovering pathways
      potentially involved in MS. Our findings provide novel insights into the
      regulatory mechanisms and networks underlying MS.

PMID- 27694857
TI  - Editorial: Statins for Inflammatory Bowel Disease: Expanding the Scope of
      Prevention.
AB  - In addition to cholesterol depletion, statins also significantly decrease
      systemic inflammation as measured by C-reactive protein. In this issue of
      American Journal of Gastroenterology, Ungaro et al. present their results on the
      associations between statin prescriptions and risk of Crohn's disease (CD) and
      ulcerative colitis (UC). Using a national medical claims and pharmacy database
      created by Symphony Health Solutions LLC (SHA), they show that any use of statin
      is protective against diagnosis of CD and UC. The protective effect against CD
      appears strongest among older populations (>60 years old). These findings offer
      intriguing insights into inflammatory pathways that could be modulated by
      cholesterol lowering drugs. In addition, if replicated in other cohorts, these
      results provide further rationale for investigating the use of statins in broader
      preventive efforts, including healthy patients at risk of developing inflammatory
      bowel disease.

PMID- 27694858
TI  - Reply to Kim J.S. and Kim B.-W.

PMID- 27694860
TI  - BactDNA as an Independent Risk Factor for Short-Term Crohn's Disease Recurrence.

PMID- 27694861
TI  - Corrigendum: Clinical Features and Outcomes of Complementary and Alternative
      Medicine Induced Acute Liver Failure and Injury.

PMID- 27694862
TI  - Metastatic Follicular Lymphoma Identified on Surveillance Colonoscopy.

PMID- 27694864
TI  - Gastric Perforation Caused by a Left Ventricular Assist Device.

PMID- 27694865
TI  - Treatment of Diffuse Esophageal Squamous Papillomatosis with Cryotherapy.

PMID- 27694866
TI  - Levofloxacin-Containing Sequential Therapy May Not Be Better than Levofloxacin
      Triple Therapy after Failure of Non-Bismuth Quadruple Therapies.

PMID- 27694867
TI  - Endoscopic Ultrasound Guided Perirectal Abscess Drainage Using a Novel Lumen
      Apposing Covered Metal Stent.

PMID- 27694868
TI  - Psychological Factors, Symptoms, and Mucosal Inflammation in Inflammatory Bowel
      Disease.

PMID- 27694869
TI  - Response to Levenstein and Prantera.

PMID- 27694871
TI  - Palliative Decompression of a Symptomatic Mucinous Adenocarcinoma of the
      Pancreas.

PMID- 27694873
TI  - Smooth-Muscle Myopathy in Systemic Lupus Erythematosus Presenting With Intestinal
      Pseudo-Obstruction.

PMID- 27694875
TI  - Gastric Mucosal Calcinosis Mimicking Malignancy.

PMID- 27694876
TI  - Editorial: Intravenous Proton Pump Inhibitors for Bleeding Peptic Ulcer: What is
      the Most Cost-Effective Approach?
AB  - During their lifetime, about 10% of the population will develop a peptic ulcer.
      Despite major advancements in the approach to peptic ulcer bleeding over the last
      10-20 years including newer endoscopic hemostatic techniques and the advent of
      proton pump inhibitors (PPIs), upper gastrointestinal bleeding due to peptic
      ulcers results in substantial morbidity, mortality, and cost. Both oral and
      intravenous PPIs have proven to be effective in preventing recurrent bleeding
      from peptic ulcers. However, the dosing and administration of PPIs have been a
      source of ongoing debate, specifically in relation to cost. In this issue of the
      Journal, Lu et al. perform cost analysis demonstrating that costs from bleeding
      peptic ulcers are influenced more by efficient triage and discharge of patients
      than the nuances of variations in administration of intravenous PPI's.

PMID- 27694877
TI  - Buried Barrett's Esophagus Presenting as a Subepithelial Nodule.

PMID- 27694878
TI  - Toward Food Therapy for Irritable Bowel Syndrome.

PMID- 27694880
TI  - Differential photosynthetic and morphological adaptations to low light affect
      depth distribution of two submersed macrophytes in lakes.
AB  - To evaluate the relative importance of photosynthetic versus morphological
      adaptations of submersed macrophytes to low light intensity in lakes, rapid light
      curves (RLCs), morphological parameters, relative growth rate (RGR), clonal
      reproduction and abundance of two submersed macrophytes (Potamogeton maackianus
      and Vallisneria natans) were examined under 2.8%, 7.1%, 17.1% and 39.5% ambient
      light in a field and outdoor experimental study. The plants increased their
      initial slope of RLCs (alpha) and decreased their minimum saturating irradiance
      (Ek) and maximum relative electron transport rate (ETRm) of RLCs under low light
      stress, but V. natans was more sensitive in RLCs than P. maackianus. Accordingly,
      the RGR, plant height and abundance of P. maackianus were higher in the high
      light regimes (shallow water) but lower in the low light regimes than those of V.
      natans. At the 2.8% ambient light, V. natans produced ramets and thus fulfilled
      its population expansion, in contrast to P. maackianus. The results revealed that
      P. maackianus as a canopy-former mainly elongated its shoot length towards the
      water surface to compensate for the low light conditions, however, it became
      limited in severe low light stress conditions. V. natans as a rosette adapted to
      low light stress mainly through photosynthetic adjustments and superior to
      severely low light than shoot elongation.

PMID- 27694881
TI  - Corrigendum: The differential short- and long-term effects of HIV-1 latency
      reversing agents on T cell function.

PMID- 27694879
TI  - Ageing increases reliance on sensorimotor prediction through structural and
      functional differences in frontostriatal circuits.
AB  - The control of voluntary movement changes markedly with age. A critical component
      of motor control is the integration of sensory information with predictions of
      the consequences of action, arising from internal models of movement. This leads
      to sensorimotor attenuation-a reduction in the perceived intensity of sensations
      from self-generated compared with external actions. Here we show that
      sensorimotor attenuation occurs in 98% of adults in a population-based cohort
      (n=325; 18-88 years; the Cambridge Centre for Ageing and Neuroscience).
      Importantly, attenuation increases with age, in proportion to reduced sensory
      sensitivity. This effect is associated with differences in the structure and
      functional connectivity of the pre-supplementary motor area (pre-SMA), assessed
      with magnetic resonance imaging. The results suggest that ageing alters the
      balance between the sensorium and predictive models, mediated by the pre-SMA and
      its connectivity in frontostriatal circuits. This shift may contribute to the
      motor and cognitive changes observed with age.

PMID- 27694882
TI  - The trafficking of bacterial type rhodopsins into the Chlamydomonas eyespot and
      flagella is IFT mediated.
AB  - The bacterial type rhodopsins are present in all the three domains of life. In
      contrast to the animal type rhodopsin that performs mainly sensory functions in
      higher eukaryotes, the bacterial type rhodopsin could function as ion channel,
      pumps and as sensory proteins. The functioning of rhodopsin in higher eukaryotes
      requires the transport of rhodopsin from its site of synthesis to the ciliated
      outer segment of the photoreceptive cells. However, the trafficking of bacterial
      type rhodopsin from its site of synthesis to the position of action is not
      characterized. Here we present the first report for the existence of an IFT
      interactome mediated trafficking of the bacterial type rhodopsins into eyespot
      and flagella of the Chlamydomonas. We show that there is a light-dependent,
      dynamic localization of rhodopsins between flagella and eyespot of Chlamydomonas.
      The involvement of IFT components in the rhodopsin trafficking was elucidated by
      the use of conditional IFT mutants. We found that rhodopsin can be co
      immunoprecipitated with the components of IFT machinery and with other protein
      components required for the IFT-cargo complex formation. These findings show that
      light-regulated localization of rhodopsin is not restricted to animals thereby
      suggesting that rhodopsin trafficking is an IFT dependent ancient process.

PMID- 27694883
TI  - Localized force application reveals mechanically sensitive domains of Piezo1.
AB  - Piezos are mechanically activated ion channels that function as sensors of touch
      and pressure in various cell types. However, the precise mechanism and structures
      mediating mechanical activation and subsequent inactivation have not yet been
      identified. Here we use magnetic nanoparticles as localized transducers of
      mechanical force in combination with pressure-clamp electrophysiology to identify
      mechanically sensitive domains important for activation and inactivation.

PMID- 27694886
TI  - Bacterial physiology: A new chaperone for regulatory sRNAs.

PMID- 27694884
TI  - SUMOylated NKAP is essential for chromosome alignment by anchoring CENP-E to
      kinetochores.
AB  - Chromosome alignment is required for accurate chromosome segregation. Chromosome
      misalignment can result in genomic instability and tumorigenesis. Here, we show
      that NF-kappaB activating protein (NKAP) is critical for chromosome alignment
      through anchoring CENP-E to kinetochores. NKAP knockdown causes chromosome
      misalignment and prometaphase arrest in human cells. NKAP dynamically localizes
      to kinetochores, and is required for CENP-E kinetochore localization. NKAP is
      SUMOylated predominantly in mitosis and the SUMOylation is needed for NKAP to
      bind CENP-E. A SUMOylation-deficient mutant of NKAP cannot support the
      localization of CENP-E on kinetochores or proper chromosome alignment. Moreover,
      Bub3 recruits NKAP to stabilize the binding of CENP-E to BubR1 at kinetochores.
      Importantly, loss of NKAP expression causes aneuploidy in cultured cells, and is
      observed in human soft tissue sarcomas. These findings indicate that NKAP is a
      novel and key regulator of mitosis, and its dysregulation might contribute to
      tumorigenesis by causing chromosomal instability.

PMID- 27694887
TI  - Earth's magnetosphere and outer radiation belt under sub-Alfvenic solar wind.
AB  - The interaction between Earth's magnetic field and the solar wind results in the
      formation of a collisionless bow shock 60,000-100,000 km upstream of our planet,
      as long as the solar wind fast magnetosonic Mach (hereafter Mach) number exceeds
      unity. Here, we present one of those extremely rare instances, when the solar
      wind Mach number reached steady values <1 for several hours on 17 January 2013.
      Simultaneous measurements by more than ten spacecraft in the near-Earth
      environment reveal the evanescence of the bow shock, the sunward motion of the
      magnetopause and the extremely rapid and intense loss of electrons in the outer
      radiation belt. This study allows us to directly observe the state of the inner
      magnetosphere, including the radiation belts during a type of solar wind
      magnetosphere coupling which is unusual for planets in our solar system but may
      be common for close-in extrasolar planets.

PMID- 27694885
TI  - Emerging pathogenic links between microbiota and the gut-lung axis.
AB  - The microbiota is vital for the development of the immune system and homeostasis.
      Changes in microbial composition and function, termed dysbiosis, in the
      respiratory tract and the gut have recently been linked to alterations in immune
      responses and to disease development in the lungs. In this Opinion article, we
      review the microbial species that are usually found in healthy gastrointestinal
      and respiratory tracts, their dysbiosis in disease and interactions with the gut
      lung axis. Although the gut-lung axis is only beginning to be understood,
      emerging evidence indicates that there is potential for manipulation of the gut
      microbiota in the treatment of lung diseases.

PMID- 27694889
TI  - Landscape mapping at sub-Antarctic South Georgia provides a protocol for
      underpinning large-scale marine protected areas.
AB  - Global biodiversity is in decline, with the marine environment experiencing
      significant and increasing anthropogenic pressures. In response marine protected
      areas (MPAs) have increasingly been adopted as the flagship approach to marine
      conservation, many covering enormous areas. At present, however, the lack of
      biological sampling makes prioritising which regions of the ocean to protect,
      especially over large spatial scales, particularly problematic. Here we present
      an interdisciplinary approach to marine landscape mapping at the sub-Antarctic
      island of South Georgia as an effective protocol for underpinning large-scale
      (105-106  km2) MPA designations. We have developed a new high-resolution (100 m)
      digital elevation model (DEM) of the region and integrated this DEM with
      bathymetry-derived parameters, modelled oceanographic data, and satellite primary
      productivity data. These interdisciplinary datasets were used to apply an
      objective statistical approach to hierarchically partition and map the benthic
      environment into physical habitats types. We assess the potential application of
      physical habitat classifications as proxies for biological structuring and the
      application of the landscape mapping for informing on marine spatial planning.

PMID- 27694888
TI  - Statistical and Ontological Analysis of Adverse Events Associated with Monovalent
      and Combination Vaccines against Hepatitis A and B Diseases.
AB  - Vaccinations often induce various adverse events (AEs), and sometimes serious AEs
      (SAEs). While many vaccines are used in combination, the effects of vaccine
      vaccine interactions (VVIs) on vaccine AEs are rarely studied. In this study, AE
      profiles induced by hepatitis A vaccine (Havrix), hepatitis B vaccine (Engerix
      B), and hepatitis A and B combination vaccine (Twinrix) were studied using the
      VAERS data. From May 2001 to January 2015, VAERS recorded 941, 3,885, and 1,624
      AE case reports where patients aged at least 18 years old were vaccinated with
      only Havrix, Engerix-B, and Twinrix, respectively. Using these data, our
      statistical analysis identified 46, 69, and 82 AEs significantly associated with
      Havrix, Engerix-B, and Twinrix, respectively. Based on the Ontology of Adverse
      Events (OAE) hierarchical classification, these AEs were enriched in the AEs
      related to behavioral and neurological conditions, immune system, and
      investigation results. Twenty-nine AEs were classified as SAEs and mainly related
      to immune conditions. Using a logistic regression model accompanied with MCMC
      sampling, 13 AEs (e.g., hepatosplenomegaly) were identified to result from VVI
      synergistic effects. Classifications of these 13 AEs using OAE and MedDRA
      hierarchies confirmed the advantages of the OAE-based method over MedDRA in AE
      term hierarchical analysis.

PMID- 27694890
TI  - An interaction between Scribble and the NADPH oxidase complex controls M1
      macrophage polarization and function.
AB  - The polarity protein Scribble (SCRIB) regulates apical-basal polarity,
      directional migration and tumour suppression in Drosophila and mammals. Here we
      report that SCRIB is an important regulator of myeloid cell functions including
      bacterial infection and inflammation. SCRIB interacts directly with the NADPH
      oxidase (NOX) complex in a PSD95/Dlg/ZO-1 (PDZ)-domain-dependent manner and is
      required for NOX-induced reactive oxygen species (ROS) generation in culture and
      in vivo. On bacterial infection, SCRIB localized to phagosomes in a leucine-rich
      repeat-dependent manner and promoted ROS production within phagosomes to kill
      bacteria. Unexpectedly, SCRIB loss promoted M1 macrophage polarization and
      inflammation. Thus, SCRIB uncouples ROS-dependent bacterial killing activity from
      M1 polarization and inflammatory functions of macrophages. Modulating the SCRIB
      NOX pathway can therefore identify ways to manage infection and inflammation with
      implications for chronic inflammatory diseases, sepsis and cancer.

PMID- 27694891
TI  - Statistical Analysis of Main and Interaction Effects on Cu(II) and Cr(VI)
      Decontamination by Nitrogen-Doped Magnetic Graphene Oxide.
AB  - A nitrogen-doped magnetic graphene oxide (NMGO) was synthesized and applied as an
      adsorbent to remove Cu(II) and Cr(VI) ions from aqueous solutions. The individual
      and combined effects of various factors (A: pH, B: temperature, C: initial
      concentration of metal ions, D: CaCl2, and E: humic acid [HA]) on the adsorption
      were analyzed by a 25-1 fractional factorial design (FFD). The results from this
      study indicated that the NMGO had higher adsorption capacities for Cu(II) ions
      than for Cr(VI) ions under most conditions, and the five selected variables
      affected the two adsorption processes to different extents. A, AC, and C were the
      very important factors and interactions for Cu(II) adsorption. For Cr(VI)
      adsorption, A, B, C, AB, and BC were found to be very important influencing
      variables. The solution pH (A) was the most important influencing factor for
      removal of both the ions. The main effects of A-E on the removal of Cu(II) were
      positive. For Cr(VI) adsorption, the main effects of A and D were negative, while
      B, C, and E were observed to have positive effects. The maximum adsorption
      capacities for Cu(II) and Cr(VI) ions over NMGO were 146.365 and 72.978 mg/g,
      respectively, under optimal process conditions.

PMID- 27694892
TI  - ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the
      extracellular matrix to drive lung cancer invasion and metastasis.
AB  - Lung cancer is the leading cause of cancer-related deaths, primarily due to
      distant metastatic disease. Metastatic lung cancer cells can undergo an
      epithelial-to-mesenchymal transition (EMT) regulated by various transcription
      factors, including a double-negative feedback loop between the microRNA-200 (miR
      200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT
      promotes malignancy remain largely undefined. Although the cell-intrinsic effects
      of EMT are important for tumor progression, the reciprocal dynamic crosstalk
      between mesenchymal cancer cells and the extracellular matrix (ECM) is equally
      critical in regulating invasion and metastasis. Investigating the collaborative
      effect of EMT and ECM in the metastatic process reveals increased collagen
      deposition in metastatic tumor tissues as a direct consequence of amplified
      collagen gene expression in ZEB1-activated mesenchymal lung cancer cells. In
      addition, collagen fibers in metastatic lung tumors exhibit greater linearity and
      organization as a result of collagen crosslinking by the lysyl oxidase (LOX)
      family of enzymes. Expression of the LOX and LOXL2 isoforms is directly regulated
      by miR-200 and ZEB1, respectively, and their upregulation in metastatic tumors
      and mesenchymal cell lines is coordinated to that of collagen. Functionally,
      LOXL2, as opposed to LOX, is the principal isoform that crosslinks and stabilizes
      insoluble collagen deposition in tumor tissues. In turn, focal adhesion formation
      and FAK/SRC signaling is activated in mesenchymal tumor cells by crosslinked
      collagen in the ECM. Our study is the first to validate direct regulation of LOX
      and LOXL2 by the miR-200/ZEB1 axis, defines a novel mechanism driving tumor
      metastasis, delineates collagen as a prognostic marker, and identifies LOXL2 as a
      potential therapeutic target against tumor progression.

PMID- 27694893
TI  - Transducin (beta)-like 1 X-linked receptor 1 promotes gastric cancer progression
      via the ERK1/2 pathway.
AB  - Gastric cancer (GC) is one of the most common types of cancer worldwide, and it
      involves extensive local tumour invasion, metastasis and poor prognosis.
      Understanding the mechanisms regulating the progression of GC is necessary for
      the development of effective therapeutic strategies. Transducin (beta)-like 1 X
      linked receptor 1 (TBL1XR1) is an important regulator controlling gene activation
      and repression, which has been thought to be involved in tumorigenesis. However,
      the role of TBL1XR1 in human GC remains largely unknown. Here, we find that
      TBL1XR1 is aberrantly expressed in human GC tissues, and TBL1XR1 levels are
      highly correlated with local tumour invasion, late tumor, lymph node, metastasis
      (TNM) stage and poor prognosis. Knockdown of TBL1XR1 by shRNA inhibits GC cell
      proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) in
      vitro, as well as tumorigenesis and peritoneal metastasis in vivo, whereas
      overexpression of TBL1XR1 produces the opposite effects. These effects are
      mediated by activation of the ERK1/2 signalling pathway, and inhibition of this
      pathway with a specific ERK1/2 inhibitor (U0126) significantly impairs the tumour
      promoting effects induced by TBL1XR1. Moreover, TBL1XR1 mediated ERK1/2
      activation is dependent on the beta-catenin/MMP7/EGFR signalling pathway. In
      conclusion, TBL1XR1 contributes to GC tumorigenesis and progression through the
      activation of the beta-catenin/MMP7/EGFR/ERK signalling pathway and may act as a
      new therapeutic target for GC.

PMID- 27694894
TI  - NPM-ALK phosphorylates WASp Y102 and contributes to oncogenesis of anaplastic
      large cell lymphoma.
AB  - Mechanisms by which NPM-ALK signaling regulates cell migration, invasion and
      contributes to the oncogenesis of anaplastic large cell lymphoma (ALCL) are not
      completely understood. In an attempt to identify novel actin signaling pathways
      regulated by NPM-ALK, a comprehensive phosphoproteome analysis of ALCL cell lines
      was performed in the presence or absence of NPM-ALK activity. Numerous
      phosphoproteins involved in actin dynamics including Wiskott-Aldrich syndrome
      protein (WASp) were regulated by NPM-ALK. Network analysis revealed that WASp is
      a central component of the NPM-ALK-dependent actin signaling pathway. Here we
      show that NPM-ALK phosphorylates WASp at its known activation site (Y290) as well
      as at a novel residue (Y102). Phosphorylation of WASp at Y102 negatively
      regulates its interaction with Wiskott-Aldrich interacting protein and decreases
      its protein stability. Phosphorylation of WASp at Y102 enhances anchorage
      independent growth and tumor growth in an in vivo xenograft model and enhances
      invasive properties of ALCL. We show that knock-down of WASp or expression of
      Y102F mutant of WASp decreases colony formation and in vivo tumor growth. Our
      results show that WASp is a novel substrate of ALK and has a critical role in
      regulating invasiveness and oncogenesis of ALCL.

PMID- 27694896
TI  - An in vivo screening system to identify tumorigenic genes.
AB  - Screening for oncogenes has mostly been performed by in vitro transformation
      assays. However, some oncogenes might not exhibit their transforming activities
      in vitro unless putative essential factors from in vivo microenvironments are
      adequately supplied. Here, we have developed an in vivo screening system that
      evaluates the tumorigenicity of target genes. This system uses a retroviral high
      efficiency gene transfer technique, a large collection of human cDNA clones
      corresponding to ~70% of human genes and a luciferase-expressing immortalized
      mouse mammary epithelial cell line (NMuMG-luc). From 845 genes that were highly
      expressed in human breast cancer cell lines, we focused on 205 genes encoding
      membrane proteins and/or kinases as that had the greater possibility of being
      oncogenes or drug targets. The 205 genes were divided into five subgroups, each
      containing 34-43 genes, and then introduced them into NMuMG-luc cells. These
      cells were subcutaneously injected into nude mice and monitored for tumor
      development by in vivo imaging. Tumors were observed in three subgroups. Using
      DNA microarray analyses and individual tumorigenic assays, we found that three
      genes, ADORA2B, PRKACB and LPAR3, were tumorigenic. ADORA2B and LPAR3 encode G
      protein-coupled receptors and PRKACB encodes a protein kinase A catalytic
      subunit. Cells overexpressing ADORA2B, LPAR3 or PRKACB did not show transforming
      phenotypes in vitro, suggesting that transformation by these genes requires in
      vivo microenvironments. In addition, several clinical data sets, including one
      for breast cancer, showed that the expression of these genes correlated with
      lower overall survival rate.

PMID- 27694895
TI  - Identification of a cancer stem cell-specific function for the histone
      deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer.
AB  - Tumours are comprised of a highly heterogeneous population of cells, of which
      only a small subset of stem-like cells possess the ability to regenerate tumours
      in vivo. These cancer stem cells (CSCs) represent a significant clinical
      challenge as they are resistant to conventional cancer therapies and play
      essential roles in metastasis and tumour relapse. Despite this realization and
      great interest in CSCs, it has been difficult to develop CSC-targeted treatments
      due to our limited understanding of CSC biology. Here, we present evidence that
      specific histone deacetylases (HDACs) play essential roles in the CSC phenotype.
      Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are
      specifically over-expressed in CSCs when compared to non-stem-tumour-cells
      (nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain
      CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC
      phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi)
      targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These
      results provide actionable insights that can be rapidly translated into CSC
      specific therapies.

PMID- 27694897
TI  - Systematic and functional characterization of novel androgen receptor variants
      arising from alternative splicing in the ligand-binding domain.
AB  - The presence of intact ligand-binding domain (LBD) ensures the strict androgen
      dependent regulation of androgen receptor (AR): binding of androgen induces
      structural reorganization of LBD resulting in release of AR from HSP90,
      suppression of nuclear export which otherwise dominates over import and nuclear
      translocation of AR as a transcription factor. Thus, loss or defects of the LBD
      abolish constraint from un-liganded LBD as exemplified by constitutively active
      AR variants (AR-Vs), which are associated with emerging resistance mechanism to
      anti-AR therapy in castration-resistant prostate cancer (mCRPC). Recent analysis
      of the AR splicing landscapes revealed mCRPC harboring multiple AR-Vs with
      diverse patterns of inclusion/exclusion of exons (exons 4-8) corresponding to LBD
      to produce namely exon-skipping variants. In silico construction for these AR-Vs
      revealed four novel AR-Vs having unique features: Exclusion of specified exons
      introduces a frameshift in variants v5es, v6es and v7es. ARv56es maintains the
      reading frame resulting in the inclusion of the C-terminal half of the LBD. We
      systematically characterized these AR-Vs regarding their subcellular
      localization, affinity for HSP90 and transactivation capability. Notably, ARv5es
      was free from HSP90, exclusively nuclear, and constitutively active similarly as
      previously reported for v567es. In contrast, v6es and v7es were similar in that
      they are cytoplasmic, transcriptionally inactive and bind HSP90, ARv56es was
      present in both nucleus and cytoplasm, does not bind HSP90 and is
      transcriptionally inactive. Converting these transcriptionally inactive AR-Vs
      into active forms, we identified the two separate elements that allosterically
      suppress otherwise constitutively active AR-Vs; one in exon 5 for v6es and v7es
      and the other in exon 8 for v56es. Our findings identify a novel constitutively
      active AR-V, ARv5es and establish a method to predict potential activities of AR
      Vs carrying impaired LBD.

PMID- 27694899
TI  - APOBEC3A associates with human papillomavirus genome integration in oropharyngeal
      cancers.
AB  - The prevalence of human papillomavirus (HPV)-related oropharyngeal cancers has
      been increasing in developed countries. We recently demonstrated that members of
      the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family,
      which are antiviral factors, can induce hypermutation of HPV DNA in vitro. In the
      present study, we found numerous C-to-T and G-to-A hypermutations in the HPV16
      genome in oropharyngeal cancer (OPC) biopsy samples using differential DNA
      denaturation PCR and next-generation sequencing. A3s were more abundantly
      expressed in HPV16-positive OPCs than in HPV-negative, as assessed using
      immunohistochemistry and reverse transcription quantitative PCR. In addition,
      interferons upregulated A3s in an HPV16-positive OPC cell line. Furthermore,
      quantitative PCR analysis of HPV DNA suggests that APOBEC3A (A3A) expression is
      strongly correlated with the integration of HPV DNA. These results suggest that
      HPV16 infection may upregulate A3A expression, thereby increasing the chance of
      viral DNA integration. The role of A3A in HPV-induced carcinogenesis is
      discussed.

PMID- 27694898
TI  - Prefoldin 1 promotes EMT and lung cancer progression by suppressing cyclin A
      expression.
AB  - Prefoldin (PFDN) is a co-chaperone protein that is primarily known for its
      classic cytoplasmic functions in the folding of actin and tubulin monomers during
      cytoskeletal assembly. Here, we report a marked increase in prefoldin subunit 1
      (PFDN1) levels during the transforming growth factor (TGF)-beta1-mediated
      epithelial-mesenchymal transition (EMT) and in human lung tumor tissues.
      Interestingly, the nuclear localization of PFDN1 was also detected. These
      observations suggest that PFDN1 may be essential for important novel functions.
      Overexpression of PFDN1 induced EMT and cell invasion. In sharp contrast,
      knockdown of PFDN1 generated the opposite effects. Overexpression of PFDN1 was
      also found to induce lung tumor growth and metastasis. Further experiments showed
      that PFDN1 overexpression inhibits the expression of cyclin A. PFDN1 suppressed
      cyclin A expression by directly interacting with the cyclin A promoter at the
      transcriptional start site. Strikingly, cyclin A overexpression abolished the
      above PFDN1-mediated effects on the behavior of lung cancer cells, whereas cyclin
      A knockdown alone induced EMT and increased cell migration and invasion ability.
      This study reveals that the TGF-beta1/PFDN1/cyclin A axis is essential for EMT
      induction and metastasis of lung cancer cells.

PMID- 27694900
TI  - Lysine-specific demethylase KDM3A regulates ovarian cancer stemness and
      chemoresistance.
AB  - Ovarian cancer is the leading cause of death among all gynecological malignancies
      due to the development of acquired chemoresistance and disease relapse. Although
      the role of cancer stem cells (CSCs), a subset of tumor cells with the self
      renewal and differentiation capabilities, in therapeutic resistance is beginning
      to be better understood, the significance of epigenetic regulatory mechanisms
      responsible for integrating the stemness with drug resistance remain poorly
      understood. Here we identified that lysine demethylase KDM3A as a critical
      regulator of ovarian cancer stemness and cisplatin resistance by inducing the
      expressions of pluripotent molecules Sox2 and Nanog and anti-apoptotic B-cell
      lymphoma 2 (Bcl-2), respectively. In addition, KDM3A induces ovarian cancer
      growth while antagonizing cellular senescence by repressing the expression of
      cyclin-dependent kinase inhibitor, p21Waf1/Cip1. The underlying mechanism of the
      noted biological processes include KDM3A-mediated stimulation of Sox2 expression,
      and demethylating p53 protein and consequently, modulating its target genes such
      as Bcl-2 and p21Waf1/Cip1 expression. Consistently, KDM3A depletion inhibited the
      growth of subcutaneously implanted cisplatin-resistant human ovarian cancer cells
      in athymic nude mice. Moreover, KDM3A is abundantly expressed and positively
      correlated with Sox2 expression in human ovarian cancer tissues. In brief, our
      findings reveal a novel mechanism by which KDM3A promotes ovarian CSCs,
      proliferation and chemoresistance and thus, highlights the significance of KDM3A
      as a novel therapeutic target for resistant ovarian cancer.

PMID- 27694901
TI  - MYC selects against reduced BCL2A1/A1 protein expression during B cell
      lymphomagenesis.
AB  - Rearrangements of MYC or ABL proto-oncogenes lead to deregulated expression of
      key-regulators of cell cycle and cell survival, thereby constituting important
      drivers of blood cancer. Members of the BCL-2 family of apoptosis regulators
      contribute to oncogenic transformation downstream of these oncogenes, but the
      role of anti-apoptotic BCL2A1/A1 in transformation and drug resistance caused by
      deregulation of these oncogenes remains enigmatic. Here we analyzed the role of
      A1 in MYC as well as ABL kinase-driven blood cancer in mice, employing in vivo
      RNAi. We report that overexpression of either oncogene leads to a significant
      increase in A1 protein levels in otherwise A1-negative B cell progenitors,
      indicating a key role downstream of these oncogenes to secure survival during
      transformation. Knockdown of A1 by RNAi, however, did not impact on tumor latency
      in v-Abl-driven pre-B-ALL. In contrast, A1 knockdown in premalignant EMU-MYC mice
      caused a significant reduction of transgenic pre-B cells without impacting on
      tumor latency as the emerging lymphomas escaped silencing of A1 expression. These
      findings identify A1 as a MYC target that can be induced prematurely during B
      cell development to aid expansion of otherwise cell-death-prone MYC transgenic
      pre-B cells. Hence, A1 should be considered as a putative drug target in MYC
      driven blood cancer.

PMID- 27694902
TI  - Functional redundancy between Apc and Apc2 regulates tissue homeostasis and
      prevents tumorigenesis in murine mammary epithelium.
AB  - Aberrant Wnt signaling within breast cancer is associated with poor prognosis,
      but regulation of this pathway in breast tissue remains poorly understood and the
      consequences of immediate or long-term dysregulation remain elusive. The exact
      contribution of the Wnt-regulating proteins adenomatous polyposis coli (APC) and
      APC2 in the pathogenesis of human breast cancer are ill-defined, but our analysis
      of publically available array data sets indicates that tumors with concomitant
      low expression of both proteins occurs more frequently in the 'triple negative'
      phenotype, which is a subtype of breast cancer with particularly poor prognosis.
      We have used mouse transgenics to delete Apc and/or Apc2 from mouse mammary
      epithelium to elucidate the significance of these proteins in mammary homeostasis
      and delineate their influences on Wnt signaling and tumorigenesis. Loss of either
      protein alone failed to affect Wnt signaling levels or tissue homeostasis.
      Strikingly, concomitant loss led to local disruption of beta-catenin status,
      disruption in epithelial integrity, cohesion and polarity, increased cell
      division and a distinctive form of ductal hyperplasia with 'squamoid' ghost cell
      nodules in young animals. Upon aging, the development of Wnt activated mammary
      carcinomas with squamous differentiation was accompanied by a significantly
      reduced survival. This novel Wnt-driven mammary tumor model highlights the
      importance of functional redundancies existing between the Apc proteins both in
      normal homeostasis and in tumorigenesis.

PMID- 27694904
TI  - Unsupervised vector-based classification of single-molecule charge transport
      data.
AB  - The stochastic nature of single-molecule charge transport measurements requires
      collection of large data sets to capture the full complexity of a molecular
      system. Data analysis is then guided by certain expectations, for example, a
      plateau feature in the tunnelling current distance trace, and the molecular
      conductance extracted from suitable histogram analysis. However, differences in
      molecular conformation or electrode contact geometry, the number of molecules in
      the junction or dynamic effects may lead to very different molecular signatures.
      Since their manifestation is a priori unknown, an unsupervised classification
      algorithm, making no prior assumptions regarding the data is clearly desirable.
      Here we present such an approach based on multivariate pattern analysis and apply
      it to simulated and experimental single-molecule charge transport data. We
      demonstrate how different event shapes are clearly separated using this algorithm
      and how statistics about different event classes can be extracted, when
      conventional methods of analysis fail.

PMID- 27694905
TI  - In Situ Growth of Highly Adhesive Surface Layer on Titanium Foil as Durable
      Counter Electrodes for Efficient Dye-sensitized Solar Cells.
AB  - Counter electrodes (CEs) of dye-sensitized solar cells (DSCs) are usually
      fabricated by depositing catalytic materials on substrates. The poor adhesion of
      the catalytic material to the substrate often results in the exfoliation of
      catalytic materials, and then the deterioration of cell performance or even the
      failure of DSCs. In this study, a highly adhesive surface layer is in situ grown
      on the titanium foil via a facile process and applied as CEs for DSCs. The DSCs
      applying such CEs demonstrate decent power conversion efficiencies, 6.26% and
      4.37% for rigid and flexible devices, respectively. The adhesion of the surface
      layer to the metal substrate is so strong that the photovoltaic performance of
      the devices is well retained even after the CEs are bended for 20 cycles and torn
      twice with adhesive tape. The results reported here indicate that the in situ
      growth of highly adhesive surface layers on metal substrate is a promising way to
      prepare durable CEs for efficient DSCs.

PMID- 27694903
TI  - Cip2a promotes cell cycle progression in triple-negative breast cancer cells by
      regulating the expression and nuclear export of p27Kip1.
AB  - Triple-negative breast cancer (TNBC) is very aggressive and currently has no
      specific therapeutic targets; as a consequence, TNBC exhibits poor clinical
      outcome. In this study, we showed that cancerous inhibitor of protein phosphatase
      2A (Cip2a) represents a promising target in TNBC because Cip2a was highly
      expressed in TNBC cells and tumor tissues, and its expression showed an inverse
      correlation with overall survival in patients with TNBC. We found that inhibition
      of Cip2a in TNBC cells induced cell cycle arrest at the G2/M phase, inhibited
      cell proliferation and delayed tumor growth in the xenograft model. Moreover,
      Cip2a markedly decreased the expression and nuclear localization of p27Kip1 and
      this is critical for the ability of Cip2a to promote TNBC progression.
      Mechanistically, our studies showed that Cip2a promoted p27Kip1 phosphoration at
      Ser10 via inhibiting Akt-associated PP2A activity, which seems to relocalize
      p27Kip1 to the cytoplasm in TNBC cells. On the other hand, Cip2a also recruited c
      myc to mediate the transcriptional inhibition of p27Kip1. Notably, we observed
      negative correlation between Cip2a and p27Kip1 expression in TNBC specimens. In
      addition, our data showed that Cip2a depletion could sensitize TNBC to PARP
      inhibition. Collectively, these data suggested that Cip2a effectively promotes
      TNBC cell cycle progression and tumor growth via regulation of PP2A/c-myc/p27Kip1
      signaling, which could serve as a potential therapeutic target for TNBC patients.

PMID- 27694906
TI  - CRISPR/Cas9 Targets Chicken Embryonic Somatic Cells In Vitro and In Vivo and
      generates Phenotypic Abnormalities.
AB  - Chickens are an invaluable model for studying human diseases, physiology and
      especially development, but have lagged in genetic applications. With the advent
      of Programmable Engineered Nucleases, genetic manipulation has become efficient,
      specific and rapid. Here, we show that the CRISPR/Cas9 system can precisely edit
      the chicken genome. We generated HIRA, TYRP1, DICER, MBD3, EZH2, and 6 other gene
      knockouts in two chicken cell lines using the CRISPR/Cas9 system, with no off
      target effects detected. We also showed that very large deletions (>75 kb) could
      be achieved. We also achieved targeted modification by homology-directed repair
      (HDR), producing MEN2A and MEN2B mutations of the RET gene. We also targeted
      DGCR8 in neural cells of the chicken embryo by in vivo electroporation. After
      FACS isolation of transfected cells, we observed appropriate sequence changes in
      DGCR8. Wholemount and frozen section antibody labelling showed reduction of DGCR8
      levels in transfected cells. In addition, there was reduced expression levels of
      DGCR8-associated genes DROSHA, YPEL1 and NGN2. We also observed morphological
      differences in neural tissue and cardiac-related tissues of transfected embryos.
      These findings demonstrate that precisely targeted genetic manipulation of the
      genome using the CRISPR/Cas9 system can be extended to the highly adaptable in
      vivo chicken embryo model.

PMID- 27694907
TI  - Physcion, a naturally occurring anthraquinone derivative, induces apoptosis and
      autophagy in human nasopharyngeal carcinoma.
AB  - AIM: Physcion is a major bioactive ingredient in the traditional Chinese medicine
      Radix et Rhizoma Rhei, which has an anthraquinone chemical structure and exhibits
      a variety of pharmacological activities including laxative, hepatoprotective,
      anti-inflammatory, anti-microbial and anti-proliferative effects. In this study
      we investigated the effect of physcion on human nasopharyngeal carcinoma in vitro
      and in vivo, as well as the mechanisms underlying the anti-tumor action. METHODS:
      The nasopharyngeal carcinoma cell line CNE2 was treated with physcion, and cell
      viability was detected using MTT and colony formation assays. Flow cytometry was
      used to assess the cell cycle arrest, mitochondrial membrane potential loss,
      apoptosis, autophagy and intracellular ROS generation. Apoptotic cell death was
      also confirmed by a TUNEL assay. The expression of target or marker molecules was
      determined using Western blotting. The activity of caspase-3, 8, and 9 was
      detected with an ELISA kit. A xenograft murine model was used to evaluate the in
      vivo anti-tumor action of physcion, the mice were administered physcion (10, 20
      mg.kg-1.d-1, ip) for 30 d. RESULTS: Treatment with physcion (5, 10, and 20
      MUmol/L) dose-dependently suppressed the cell viability and colony formation in
      CNE2 cells. Physcion (10 and 20 MUmol/L) dose-dependently blocked cell cycle
      progression at G1 phase and induced both caspase-dependent apoptosis and
      autophagy in CNE2 cells. Furthermore, physcion treatment induced excessive ROS
      generation in CNE2 cells, and subsequently disrupted the miR-27a/ZBTB10 axis,
      resulting in repression of the transcription factor Sp1 that was involved in
      physcion-induced apoptosis and autophagy. Moreover, physcion-induced autophagy
      acted as a pro-apoptotic factor, and possibly contributed to physcion-induced
      apoptosis. In the xenograft murine model, administration of physcion dose
      dependently suppressed the tumor growth without affecting the body weight.
      Furthermore, the anti-tumor effects of physcion were correlated with
      downregulation of Sp1 and suppression of miR-27a in the tumor tissues.
      CONCLUSION: Physcion induces apoptosis and autophagy in human nasopharyngeal
      carcinoma by targeting Sp1, which was mediated by ROS/miR-27a/ZBTB10 signaling.
      The results suggest that physcion is a promising candidate for the treatment of
      human nasopharyngeal carcinoma.

PMID- 27694908
TI  - Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic
      mice by ameliorating both Abeta and Tau pathologies.
AB  - Considering the complicated pathogenesis of Alzheimer's disease (AD), multi
      targets have become a focus in the discovery of drugs for treatment of this
      disease. In the current work, we established a multi-target strategy for
      discovering active reagents capable of suppressing both Abeta level and Tau
      hyperphosphorylation from natural products, and found that the ethanol extract of
      Thamnolia vermicularis (THA) was able to improve learning ability in APP/PS1
      transgenic mice by inhibiting both Abeta levels and Tau hyperphosphorylation. SH
      SY5Y and CHO-APP/BACE1 cells and primary astrocytes were used in cell-based
      assays. APP/PS1 transgenic mice [B6C3-Tg(APPswe, PS1dE9)] were administered THA
      (300 mg.kg-1.d-1, ig) for 100 d. After the administration was completed, the
      learning ability of the mice was detected using a Morris water maze (MWM) assay;
      immunofluorescence staining, Congo red staining and Thioflavine S staining were
      used to detect the senile plaques in the brains of the mice. ELISA was used to
      evaluate Abeta and sAPPbeta contents, and Western blotting and RT-PCR were used
      to investigate the relevant signaling pathway regulation in response to THA
      treatment. In SH-SY5Y cells, THAlpha (1, 10, 20 MUg/mL) significantly stimulated
      PI3K/AKT/mTOR and AMPK/raptor/mTOR signaling-mediated autophagy in the promotion
      of Abeta clearance as both a PI3K inhibitor and an AMPK indirect activator, and
      restrained Abeta production as a suppressor against PERK/eIF2alpha-mediated BACE1
      expression. Additionally, THA functioned as a GSK3beta inhibitor with an IC50 of
      1.32+/-0.85 MUg/mL, repressing Tau hyperphosphorylation. Similar effects on Abeta
      accumulation and Tau hyperphosphorylation were observed in APP/PS1 transgenic
      mice treated with THA. Furthermore, administration of THA effectively improved
      the learning ability of APP/PS1 transgenic mice, and markedly reduced the number
      of senile plaques in their hippocampus and cortex. The results highlight the
      potential of the natural product THA for the treatment of AD.

PMID- 27694909
TI  - Inhibitory effects of hesperetin on Nav1.5 channels stably expressed in HEK 293
      cells and on the voltage-gated cardiac sodium current in human atrial myocytes.
AB  - AIM: Voltage-gated sodium channels composed of a pore-forming alpha subunit and
      auxiliary beta subunits are responsible for the upstroke of the action potential
      in cardiac myocytes. The pore-forming subunit of the cardiac sodium channel
      Nav1.5, which is encoded by SCN5A, is the main ion channel that conducts the
      voltage-gated cardiac sodium current (INa) in cardiac cells. The current study
      sought to investigate the inhibitory effects of hesperetin on human cardiac
      Nav1.5 channels stably expressed in human embryonic kidney 293 (HEK 293) cells
      and on the voltage-gated cardiac sodium current (INa) in human atrial myocytes.
      METHODS: The effects of hesperetin on human cardiac Nav1.5 channels expressed in
      HEK 293 cells and on cardiac Na+ currents in human atrial myocytes were examined
      through whole-cell patch-clamp techniques. RESULTS: Nav1.5 currents were potently
      and reversibly suppressed in a concentration- and voltage-dependent manner by
      hesperetin, which exhibited an IC50 of 62.99 MUmol/L. Hesperetin significantly
      and negatively shifted the voltage-dependent activation and inactivation curves.
      Hesperetin also markedly decelerated Nav1.5 current inactivation and slowed the
      recovery from Nav1.5 channel inactivation. The hesperetin-dependent blockage of
      Nav1.5 currents was frequency-dependent. Hesperetin also potently and reversibly
      inhibited Na+ current (INa) in human atrial myocytes, consistently with its
      effects on Nav1.5 currents in HEK 293 cells. CONCLUSION: Hesperetin is a potent
      inhibitor of INa in human atrial myocytes and Nav1.5 channels expressed in human
      embryonic kidney 293 cells. Hesperetin probably functions by blocking the open
      state and the inactivated state of these channels.

PMID- 27694910
TI  - Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of
      sulfonylureas in Chinese patients with type 2 diabetes.
AB  - KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like
      subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus
      for type 2 diabetes mellitus (T2DM). In the present study, we examined the
      effects of KCNQ1 variants on the therapeutic response to modified-release
      gliclazide (gliclazide MR) treatment in Chinese patients newly diagnosed with
      T2DM. A total of 100 newly diagnosed T2DM patients without a history of any anti
      diabetic medications were treated with gliclazide MR for 16 weeks, but 91
      patients completed the entire study. The anthropometric parameters were
      determined at baseline and at the final visit, while clinical laboratory tests
      were performed at baseline and on weeks 2, 4, 6, 12, 16. Two SNPs, rs2237892 and
      rs2237895, in the region of the KCNQ1 gene were genotyped in all the
      participants. All calculations and statistical analyses were conducted using
      SPSS. The rs2237892 TT homozygotes exhibited significantly higher 2-h glucose
      levels at baseline (P<0.05) and a lower cumulative attainment rate of the target
      2-h glucose level (Plog-rank=0.020) than the C allele carriers. Patients with
      greater numbers of rs2237892 T alleles exhibited larger augmentations (Delta) in
      the 2-h glucose levels (P=0.027); and patients with the rs2237892 TT genotype
      exhibited a higher Delta homeostasis model assessment of beta-cell function (HOMA
      beta) than CC and CT genotype carriers (P=0.021 and P=0.043, respectively).
      Moreover, the rs2237895 C allele was associated with a greater decrement in Delta
      glycated hemoglobin (HbA1c) (P=0.024); and patients with the CC genotype
      exhibited greater variance than those with the AA and AC genotypes (P=0.005 and
      0.021, respectively). Compared with the C allele, the odds ratio for treatment
      success among carriers of the rs2237892 T allele was 2.533 (P=0.007); and the
      rs2237895 C allele was associated with a 2.360-fold decrease in HbA1c compared
      with the A allele (P=0.009). KCNQ1 polymorphisms are associated with gliclazide
      MR efficacy in Chinese patients with type 2 diabetes.

PMID- 27694911
TI  - Massively parallel single-nucleotide mutagenesis using reversibly terminated
      inosine.
AB  - Large-scale mutagenesis of target DNA sequences allows researchers to
      comprehensively assess the effects of single-nucleotide changes. Here we
      demonstrate the construction of a systematic allelic series (SAS) using massively
      parallel single-nucleotide mutagenesis with reversibly terminated deoxyinosine
      triphosphates (rtITP). We created a mutational library containing every possible
      single-nucleotide mutation surrounding the active site of the TEM-1 beta
      lactamase gene. When combined with high-throughput functional assays, SAS
      mutational libraries can expedite the functional assessment of genetic variation.

PMID- 27694912
TI  - A bacterial genetic selection system for ubiquitylation cascade discovery.
AB  - About one-third of the eukaryotic proteome undergoes ubiquitylation, but the
      enzymatic cascades leading to substrate modification are largely unknown. We
      present a genetic selection tool that utilizes Escherichia coli, which lack
      deubiquitylases, to identify interactions along ubiquitylation cascades.
      Coexpression of split antibiotic resistance protein tethered to ubiquitin and
      ubiquitylation target together with a functional ubiquitylation apparatus results
      in a covalent assembly of the resistance protein, giving rise to bacterial growth
      on selective media. We applied the selection system to uncover an E3 ligase from
      the pathogenic bacteria EHEC and to identify the epsin ENTH domain as an
      ultraweak ubiquitin-binding domain. The latter was complemented with a structure
      function analysis of the ENTH-ubiquitin interface. We also constructed and
      screened a yeast fusion library, discovering Sem1 as a novel ubiquitylation
      substrate of Rsp5 E3 ligase. Collectively, our selection system provides a robust
      high-throughput approach for genetic studies of ubiquitylation cascades and for
      small-molecule modulator screening.

PMID- 27694914
TI  - Prediction of postoperative liver regeneration from clinical information using a
      data-led mathematical model.
AB  - Although the capacity of the liver to recover its size after resection has
      enabled extensive liver resection, post-hepatectomy liver failure remains one of
      the most lethal complications of liver resection. Therefore, it is clinically
      important to discover reliable predictive factors after resection. In this study,
      we established a novel mathematical framework which described post-hepatectomy
      liver regeneration in each patient by incorporating quantitative clinical data.
      Using the model fitting to the liver volumes in series of computed tomography of
      123 patients, we estimated liver regeneration rates. From the estimation, we
      found patients were divided into two groups: i) patients restored the liver to
      its original size (Group 1, n = 99); and ii) patients experienced a significant
      reduction in size (Group 2, n = 24). From discriminant analysis in 103 patients
      with full clinical variables, the prognosis of patients in terms of liver
      recovery was successfully predicted in 85-90% of patients. We further validated
      the accuracy of our model prediction using a validation cohort (prediction = 84
      87%, n = 39). Our interdisciplinary approach provides qualitative and
      quantitative insights into the dynamics of liver regeneration. A key strength is
      to provide better prediction in patients who had been judged as acceptable for
      resection by current pragmatic criteria.

PMID- 27694915
TI  - Integration and exchange of split dCas9 domains for transcriptional controls in
      mammalian cells.
AB  - Programmable and precise regulation of dCas9 functions in response to multiple
      molecular signals by using synthetic gene circuits will expand the application of
      the CRISPR-Cas technology. However, the application of CRISPR-Cas therapeutic
      circuits is still challenging due to the restrictive cargo size of existing viral
      delivery vehicles. Here, we construct logic AND circuits by integrating multiple
      split dCas9 domains, which is useful to reduce the size of synthetic circuits. In
      addition, we engineer sensory switches by exchanging split dCas9 domains,
      allowing differential regulations on one gene, or activating two different genes
      in response to cell-type specific microRNAs. Therefore, we provide a valuable
      split-dCas9 toolkit to engineer complex transcription controls, which may inspire
      new biomedical applications.

PMID- 27694913
TI  - Crosstalk between autophagy and inflammatory signalling pathways: balancing
      defence and homeostasis.
AB  - Autophagy has broad functions in immunity, ranging from cell-autonomous defence
      to coordination of complex multicellular immune responses. The successful
      resolution of infection and avoidance of autoimmunity necessitates efficient and
      timely communication between autophagy and pathways that sense the immune
      environment. The recent literature indicates that a variety of immune mediators
      induce or repress autophagy. It is also becoming increasingly clear that immune
      signalling cascades are subject to regulation by autophagy, and that a return to
      homeostasis following a robust immune response is critically dependent on this
      pathway. Importantly, examples of non-canonical forms of autophagy in mediating
      immunity are pervasive. In this article, the progress in elucidating mechanisms
      of crosstalk between autophagy and inflammatory signalling cascades is reviewed.
      Improved mechanistic understanding of the autophagy machinery offers hope for
      treating infectious and inflammatory diseases.

PMID- 27694916
TI  - Electrochemical aptasensor for lung cancer-related protein detection in crude
      blood plasma samples.
AB  - The development of an aptamer-based electrochemical sensor for lung cancer
      detection is presented in this work. A highly specific DNA-aptamer, LC-18,
      selected to postoperative lung cancer tissues was immobilized onto a gold
      microelectrode and electrochemical measurements were performed in a solution
      containing the redox marker ferrocyanide/ferricyanide. The aptamer protein
      targets were harvested from blood plasma of lung cancer patients by using
      streptavidin paramagnetic beads and square wave voltammetry of the samples was
      performed at various concentrations. In order to enhance the sensitivity of the
      aptasensor, silica-coated iron oxide magnetic beads grafted with hydrophobic C8
      and C4 alkyl groups were used in a sandwich detection approach. Addition of
      hydrophobic beads increased the detection limit by 100 times. The detection limit
      of the LC-18 aptasensor was enhanced by the beads to 0.023 ng/mL. The formation
      of the aptamer - protein - bead sandwich on the electrode surface was visualized
      by electron microcopy. As a result, the electrochemical aptasensor was able to
      detect cancer-related targets in crude blood plasma of lung cancer patients.

PMID- 27694918
TI  - GDGT distribution in a stratified lake and implications for the application of
      TEX86 in paleoenvironmental reconstructions.
AB  - We investigated the relationship between distributions of GDGTs, GDGT-based
      proxies and environmental factors in a stratified lake in northwestern Norway.
      More than 90% of isoGDGTs were produced at the bottom of the oxycline, indicating
      a predominance of ammonia-oxidizing Group I.1a of Thaumarchaeota, supported by
      high crenarchaeol/caldarchaeol ratios. Dissolved oxygen content, rather than
      temperature, exercised a primary control on TEX86 values. In spite of low BIT
      value in surface sediment, the reconstructed lake surface temperature was "cold"
      biased. MBT values in streams and lake surface water were significantly smaller
      than those in the catchment soil, suggesting in situ production of brGDGTs in
      streams. A rapid transition of MBT vs. temperature/pH relationships occurring at
      the bottom of oxycline indicated the differential production of various brGDGTs
      with D.O. and depths. Only within the oxycline were CBT-based pH values close to
      in situ pH. Our results confirm earlier studies calling for caution in applying
      TEX86 as a surface temperature proxy, or MBT and/or CBT for reconstructing pH, in
      anoxic or euxinic lakes, estuaries and ocean basins. We propose that
      caldarchaeol/crenarchaeol ratio, an indicator of contributions from methanogenic
      archaea, together with the BIT and TEX86 proxies, can help reconstruct past
      levels of stratification.

PMID- 27694917
TI  - Soybean GmDREBL Increases Lipid Content in Seeds of Transgenic Arabidopsis.
AB  - A DREB-type transcription factor gene GmDREBL has been characterized for its
      functions in oil accumulation in seeds. The gene is specifically expressed in
      soybean seeds. The GmDREBL is localized in nucleus and has transcriptional
      activation ability. Overexpression of GmDREBL increased the fatty acid content in
      the seeds of transgenic Arabidopsis plants. GmDREBL can bind to the promoter
      region of WRI1 to activate its expression. Several other genes in the fatty acid
      biosynthesis pathway were also enhanced in the GmDREBL-transgenic plants. The
      GmDREBL can be up-regulated by GmABI3 and GmABI5. Additionally, overexpression of
      GmDREBL significantly promoted seed size in transgenic plants compared to that of
      WT plants. Expression of the DREBL is at higher level on the average in
      cultivated soybeans than that in wild soybeans. The promoter of the DREBL may
      have been subjected to selection during soybean domestication. Our results
      demonstrate that GmDREBL participates in the regulation of fatty acid
      accumulation by controlling the expression of WRI1 and its downstream genes, and
      manipulation of the gene may increase the oil contents in soybean plants. Our
      study provides novel insights into the function of DREB-type transcription
      factors in oil accumulation in addition to their roles in stress response.

PMID- 27694920
TI  - Neural Activities Underlying the Feedback Express Salience Prediction Errors for
      Appetitive and Aversive Stimuli.
AB  - Feedback information is essential for us to adapt appropriately to the
      environment. The feedback-related negativity (FRN), a frontocentral negative
      deflection after the delivery of feedback, has been found to be larger for
      outcomes that are worse than expected, and it reflects a reward prediction error
      derived from the midbrain dopaminergic projections to the anterior cingulate
      cortex (ACC), as stated in reinforcement learning theory. In contrast, the
      prediction of response-outcome (PRO) model claims that the neural activity in the
      mediofrontal cortex (mPFC), especially the ACC, is sensitive to the violation of
      expectancy, irrespective of the valence of feedback. Additionally, increasing
      evidence has demonstrated significant activities in the striatum, anterior insula
      and occipital lobe for unexpected outcomes independently of their valence. Thus,
      the neural mechanism of the feedback remains under dispute. Here, we investigated
      the feedback with monetary reward and electrical pain shock in one task via
      functional magnetic resonance imaging. The results revealed significant
      prediction-error-related activities in the bilateral fusiform gyrus, right middle
      frontal gyrus and left cingulate gyrus for both money and pain. This implies that
      some regions underlying the feedback may signal a salience prediction error
      rather than a reward prediction error.

PMID- 27694919
TI  - Phycocyanin Inhibits Tumorigenic Potential of Pancreatic Cancer Cells: Role of
      Apoptosis and Autophagy.
AB  - Pancreatic adenocarcinoma (PDA) is one of the most lethal human malignancies, and
      unresponsive to current chemotherapies. Here we investigate the therapeutic
      potential of phycocyanin as an anti-PDA agent in vivo and in vitro. Phycocyanin,
      a natural product purified from Spirulina, effectively inhibits the pancreatic
      cancer cell proliferation in vitro and xenograft tumor growth in vivo.
      Phycocyanin induces G2/M cell cycle arrest, apoptotic and autophagic cell death
      in PANC-1 cells. Inhibition of autophagy by targeting Beclin 1 using siRNA
      significantly suppresses cell growth inhibition and death induced by phycocyanin,
      whereas inhibition of both autophagy and apoptosis rescues phycocyanin-mediated
      cell death. Mechanistically, cell death induced by phycocyanin is the result of
      cross-talk among the MAPK, Akt/mTOR/p70S6K and NF-kappaB pathways. Phycocyanin is
      able to induce apoptosis of PANC-1 cell by activating p38 and JNK signaling
      pathways while inhibiting Erk pathway. On the other hand, phycocyanin promotes
      autophagic cell death by inhibiting PI3/Akt/mTOR signaling pathways. Furthermore,
      phycocyanin promotes the activation and nuclear translocation of NF-kappaB, which
      plays an important role in balancing phycocyanin-mediated apoptosis and autosis.
      In conclusion, our studies demonstrate that phycocyanin exerts anti-pancreatic
      cancer activity by inducing apoptotic and autophagic cell death, thereby
      identifying phycocyanin as a promising anti-pancreatic cancer agent.

PMID- 27694922
TI  - Electrosprayed Multi-Core Alginate Microcapsules as Novel Self-Healing
      Containers.
AB  - Alginate microcapsules containing epoxy resin were developed through
      electrospraying method and embedded into epoxy matrix to produce a capsule-based
      self-healing composite system. These formaldehyde free alginate/epoxy
      microcapsules were characterized via light microscope, field emission scanning
      electron microscope, fourier transform infrared spectroscopy and
      thermogravimetric analysis. Results showed that epoxy resin was successfully
      encapsulated within alginate matrix to form porous (multi-core) microcapsules
      with pore size ranged from 5-100 MUm. The microcapsules had an average size of
      320 +/- 20 MUm with decomposition temperature at 220  degrees C. The loading
      capacity of these capsules was estimated to be 79%. Under in situ healing test,
      impact specimens showed healing efficiency as high as 86% and the ability to heal
      up to 3 times due to the multi-core capsule structure and the high impact energy
      test that triggered the released of epoxy especially in the second and third
      healings. TDCB specimens showed one-time healing only with the highest healing
      efficiency of 76%. The single healing event was attributed by the constant crack
      propagation rate of TDCB fracture test. For the first time, a cost effective,
      environmentally benign and sustainable capsule-based self-healing system with
      multiple healing capabilities and high healing performance was developed.

PMID- 27694921
TI  - Tea polyphenols inhibit the activation of NF-kappaB and the secretion of
      cytokines and matrix metalloproteinases by macrophages stimulated with
      Fusobacterium nucleatum.
AB  - Fusobacterium nucleatum has been associated with both periodontal disease and
      inflammatory bowel disease. This Gram-negative bacterium possesses a high
      inflammatory potential that may contribute to the disease process. We
      hypothesized that green and black tea polyphenols attenuate the inflammatory
      response of monocytes/macrophages mediated by F. nucleatum. We first showed that
      the tea extracts, EGCG and theaflavins reduce the NF-kappaB activation induced by
      F. nucleatum in monocytes. Since NF-kappaB is a key regulator of genes coding for
      inflammatory mediators, we tested the effects of tea polyphenols on secretion of
      IL-1beta, IL-6, TNF-alpha, and CXCL8 by macrophages. A pre-treatment of
      macrophages with the tea extracts, EGCG, or theaflavins prior to a stimulation
      with F. nucleatum significantly inhibited the secretion of all four cytokines and
      reduced the secretion of MMP-3 and MMP-9, two tissue destructive enzymes. TREM-1
      expressed by macrophages is a cell-surface receptor involved in the propagation
      of the inflammatory response to bacterial challenges. Interestingly, tea
      polyphenols inhibited the secretion/shedding of soluble TREM-1 induced by a
      stimulation of macrophages with F. nucleatum. The anti-inflammatory properties of
      tea polyphenols identified in the present study suggested that they may be
      promising agents for the prevention and/or treatment of periodontal disease and
      inflammatory bowel disease.

PMID- 27694923
TI  - The calcineurin protein phosphatase is dispensable for BCR-ABL-induced B-ALL
      maintenance, propagation and response to dasatinib.

PMID- 27694924
TI  - Impact of combinatorial dysfunctions of Tet2 and Ezh2 on the epigenome in the
      pathogenesis of myelodysplastic syndrome.
AB  - Somatic inactivating mutations in epigenetic regulators are frequently found in
      combination in myelodysplastic syndrome (MDS). However, the mechanisms by which
      combinatory mutations in epigenetic regulators promote the development of MDS
      remain unknown. Here we performed epigenomic profiling of hematopoietic
      progenitors in MDS mice hypomorphic for Tet2 following the loss of the polycomb
      group gene Ezh2 (Tet2KD/KDEzh2Delta/Delta). Aberrant DNA methylation propagated
      in a sequential manner from a Tet2-insufficient state to advanced MDS with
      deletion of Ezh2. Hyper-differentially methylated regions (hyper-DMRs) in
      Tet2KD/KDEzh2Delta/Delta MDS hematopoietic stem/progenitor cells were largely
      distinct from those in each single mutant and correlated with transcriptional
      repression. Although Tet2 hypomorph was responsible for enhancer
      hypermethylation, the loss of Ezh2 induced hyper-DMRs that were enriched for CpG
      islands of polycomb targets. Notably, Ezh2 targets largely lost the H3K27me3 mark
      while acquiring a significantly higher level of DNA methylation than Ezh1 targets
      that retained the mark. These findings indicate that Ezh2 targets are the major
      targets of the epigenetic switch in MDS with Ezh2 insufficiency. Our results
      provide a detailed trail for the epigenetic drift in a well-defined MDS model and
      demonstrate that the combined dysfunction of epigenetic regulators cooperatively
      remodels the epigenome in the pathogenesis of MDS.

PMID- 27694925
TI  - Hyperhaploidy is a novel high-risk cytogenetic subgroup in multiple myeloma.
AB  - Hyperhaploid clones (24-34 chromosomes) were identified in 33 patients with
      multiple myeloma (MM), demonstrating a novel numerical cytogenetic subgroup.
      Strikingly, all hyperhaploid karyotypes were found to harbor monosomy 17p, the
      single most important risk stratification lesion in MM. A catastrophic loss of
      nearly a haploid set of chromosomes results in disomies of chromosomes 3, 5, 7,
      9, 11, 15, 18, 19 and 21, the same basic set of odd-numbered chromosomes found in
      trisomy in hyperdiploid myeloma. All other autosomes are found in monosomy,
      resulting in additional clinically relevant monosomies of 1p, 6q, 13q and 16q.
      Hypotriploid subclones (58-68 chromosomes) were also identified in 11 of the 33
      patients and represent a duplication of the hyperhaploid clone. Analysis of
      clones utilizing interphase fluorescence in situ hybridization (iFISH), metaphase
      FISH and spectral karyotyping identified either monosomy 17 or del17p in all
      patients. Amplification of 1q21 was identified in eight patients, demonstrating
      an additional high-risk marker. Importantly, our findings indicate that current
      iFISH strategies may be uninformative or ambiguous in the detection of these
      clones, suggesting this patient subgroup maybe underreported. Overall survival
      for patients with hyperhaploid clones was poor, with a 5-year survival rate of
      23.1%. These findings identify a distinct numerical subgroup with cytogenetically
      defined high-risk disease.

PMID- 27694926
TI  - NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecular
      homogenous group with a poor prognosis.
AB  - Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is
      highly variable according to factors such as chromosomal abnormalities. Recurrent
      genomic rearrangements are detected in half of pediatric AML by karyotype.
      NUcleoPorin 98 (NUP98) gene is rearranged with 31 different fusion partner genes.
      These rearrangements are frequently undetected by conventional cytogenetics, as
      the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By
      screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22
      cases (3.8%), a frequency similar to CBFB-MYH11 fusion gene (4.0%). The most
      frequent NUP98 fusion gene partner is NSD1. These cases are homogeneous regarding
      their biological and clinical characteristics, and associated with bad prognosis
      only improved by bone marrow transplantation. We detailed the biological
      characteristics of these AML by exome sequencing which demonstrated few recurrent
      mutations (FLT3 ITD, WT1, CEBPA, NBPF14, BCR and ODF1). The analysis of the
      clonal structure in these cases suggests that the mutation order in the NUP98
      rearranged pediatric AML begins with the NUP98 rearrangement leading to
      epigenetic dysregulations then followed by mutations of critical hematopoietic
      transcription factors and finally, activation of the FLT3 signaling pathway.

PMID- 27694928
TI  - Nuclear FOXM1 drives chemoresistance in AML.

PMID- 27694927
TI  - A genome-wide association study identifies risk loci for childhood acute
      lymphoblastic leukemia at 10q26.13 and 12q23.1.
AB  - Genome-wide association studies (GWASs) have shown that common genetic variation
      contributes to the heritable risk of childhood acute lymphoblastic leukemia
      (ALL). To identify new susceptibility loci for the largest subtype of ALL, B-cell
      precursor ALL (BCP-ALL), we conducted a meta-analysis of two GWASs with
      imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658
      cases and 7224 controls). After genotyping an additional 2525 cases and 3575
      controls, we identify new susceptibility loci for BCP-ALL mapping to 10q26.13
      (rs35837782, LHPP, P=1.38 * 10-11) and 12q23.1 (rs4762284, ELK3, P=8.41 * 10-9).
      We also provide confirmatory evidence for the existence of independent risk loci
      at 9p21.3, but show that the association marked by rs77728904 can be accounted
      for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr
      variant rs3731249. Our data provide further insights into genetic susceptibility
      to ALL and its biology.

PMID- 27694929
TI  - Distinct surveillance pathway for immunopathology during acute infection via
      autophagy and SR-BI.
AB  - The mechanisms protecting from immunopathology during acute bacterial infections
      are incompletely known. We found that in response to apoptotic immune cells and
      live or dead Listeria monocytogenes scavenger receptor BI (SR-BI), an anti
      atherogenic lipid exchange mediator, activated internalization mechanisms with
      characteristics of macropinocytosis and, assisted by Golgi fragmentation,
      initiated autophagic responses. This was supported by scavenger receptor-induced
      local increases in membrane cholesterol concentrations which generated lipid
      domains particularly in cell extensions and the Golgi. SR-BI was a key driver of
      beclin-1-dependent autophagy during acute bacterial infection of the liver and
      spleen. Autophagy regulated tissue infiltration of neutrophils, suppressed
      accumulation of Ly6C+ (inflammatory) macrophages, and prevented hepatocyte
      necrosis in the core of infectious foci. Perifocal levels of Ly6C+ macrophages
      and Ly6C- macrophages were unaffected, indicating predominant regulation of the
      focus core. SR-BI-triggered autophagy promoted co-elimination of apoptotic immune
      cells and dead bacteria but barely influenced bacterial sequestration and
      survival or inflammasome activation, thus exclusively counteracting damage
      inflicted by immune responses. Hence, SR-BI- and autophagy promote a surveillance
      pathway that partially responds to products of antimicrobial defenses and
      selectively prevents immunity-induced damage during acute infection. Our findings
      suggest that control of infection-associated immunopathology can be based on a
      unified defense operation.

PMID- 27694930
TI  - Low Concentration of Sodium Butyrate from Ultrabraid+NaBu suture, Promotes
      Angiogenesis and Tissue Remodelling in Tendon-bones Injury.
AB  - Sodium butyrate (NaBu), a form of short-chain fatty acid (SCFA), acts classically
      as a potent anti-angiogenic agent in tumour angiogenesis models, some authors
      demonstrated that low concentrations of NaBu may contribute to healing of tendon
      bone injury in part at least through promotion of tissue remodelling. Here, we
      investigated the effects of low-range concentrations of NaBu using in vitro and
      in vivo assays using angiogenesis as the primary outcome measure and the
      mechanisms through which it acts. We demonstrated that NaBu, alone or perfused
      from the UltraBraid+NaBu suture was pro-angiogenic at very low-range doses
      promoting migration, tube formation and cell invasion in bovine aortic
      endothelial cells (BAECs). Furthermore, cell exposure to low NaBu concentrations
      increased expression of proteins involved in angiogenic cell signalling,
      including p-PKCbeta1, p-FAK, p-ERK1/2, p-NFkappabeta, p-PLCgamma1 and p-VEGFR2.
      In addition, inhibitors of both VEGFR2 and PKCbeta1 blocked the angiogenic
      response. In in vivo assays, low concentrations of NaBu induced
      neovascularization in sponge implants in mice, evidenced by increased numbers of
      vessels and haemoglobin content in these implants. The findings in this study
      indicate that low concentrations of NaBu could be an important compound to
      stimulate angiogenesis at a site where vasculature is deficient and healing is
      compromised.

PMID- 27694931
TI  - Zika viral dynamics and shedding in rhesus and cynomolgus macaques.
AB  - Infection with Zika virus has been associated with serious neurological
      complications and fetal abnormalities. However, the dynamics of viral infection,
      replication and shedding are poorly understood. Here we show that both rhesus and
      cynomolgus macaques are highly susceptible to infection by lineages of Zika virus
      that are closely related to, or are currently circulating in, the Americas. After
      subcutaneous viral inoculation, viral RNA was detected in blood plasma as early
      as 1 d after infection. Viral RNA was also detected in saliva, urine,
      cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions.
      Although viral RNA during primary infection was cleared from blood plasma and
      urine within 10 d, viral RNA was detectable in saliva and seminal fluids until
      the end of the study, 3 weeks after the resolution of viremia in the blood. The
      control of primary Zika virus infection in the blood was correlated with rapid
      innate and adaptive immune responses. We also identified Zika RNA in tissues,
      including the brain and male and female reproductive tissues, during early and
      late stages of infection. Re-infection of six animals 45 d after primary
      infection with a heterologous strain resulted in complete protection, which
      suggests that primary Zika virus infection elicits protective immunity. Early
      invasion of Zika virus into the nervous system of healthy animals and the extent
      and duration of shedding in saliva and semen underscore possible concern for
      additional neurologic complications and nonarthropod-mediated transmission in
      humans.

PMID- 27694932
TI  - Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor
      cell renewal and prevent severe pulmonary fibrosis in mice.
AB  - Successful recovery from lung injury requires the repair and regeneration of
      alveolar epithelial cells to restore the integrity of gas-exchanging regions
      within the lung and preserve organ function. Improper regeneration of the
      alveolar epithelium is often associated with severe pulmonary fibrosis, the
      latter of which involves the recruitment and activation of fibroblasts, as well
      as matrix accumulation. Type 2 alveolar epithelial cells (AEC2s) are stem cells
      in the adult lung that contribute to the lung repair process. The mechanisms that
      regulate AEC2 renewal are incompletely understood. We provide evidence that
      expression of the innate immune receptor Toll-like receptor 4 (TLR4) and the
      extracellular matrix glycosaminoglycan hyaluronan (HA) on AEC2s are important for
      AEC2 renewal, repair of lung injury and limiting the extent of fibrosis. Either
      deletion of TLR4 or HA synthase 2 in surfactant-protein-C-positive AEC2s leads to
      impaired renewal capacity, severe fibrosis and mortality. Furthermore, AEC2s from
      patients with severe pulmonary fibrosis have reduced cell surface HA and impaired
      renewal capacity, suggesting that HA and TLR4 are key contributors to lung stem
      cell renewal and that severe pulmonary fibrosis is the result of distal
      epithelial stem cell failure.

PMID- 27694933
TI  - Classification and characterization of microsatellite instability across 18
      cancer types.
AB  - Microsatellite instability (MSI), the spontaneous loss or gain of nucleotides
      from repetitive DNA tracts, is a diagnostic phenotype for gastrointestinal,
      endometrial, and colorectal tumors, yet the landscape of instability events
      across a wider variety of cancer types remains poorly understood. To explore MSI
      across malignancies, we examined 5,930 cancer exomes from 18 cancer types at more
      than 200,000 microsatellite loci and constructed a genomic classifier for MSI. We
      identified MSI-positive tumors in 14 of the 18 cancer types. We also identified
      loci that were more likely to be unstable in particular cancer types, resulting
      in specific instability signatures that involved cancer-associated genes,
      suggesting that instability patterns reflect selective pressures and can
      potentially identify novel cancer drivers. We also observed a correlation between
      survival outcomes and the overall burden of unstable microsatellites, suggesting
      that MSI may be a continuous, rather than discrete, phenotype that is informative
      across cancer types. These analyses offer insight into conserved and cancer
      specific properties of MSI and reveal opportunities for improved methods of
      clinical MSI diagnosis and cancer gene discovery.

PMID- 27694935
TI  - Interplay between hydrophilicity and surface barriers on water transport in
      zeolite membranes.
AB  - A comprehensive understanding of molecular transport within nanoporous materials
      remains elusive in a broad variety of engineering and biomedical applications.
      Here, experiments and atomistic simulations are synergically used to elucidate
      the non-trivial interplay between nanopore hydrophilicity and surface barriers on
      the overall water transport through zeolite crystals. At these nanometre-length
      scales, these results highlight the dominating effect of surface imperfections
      with reduced permeability on the overall water transport. A simple diffusion
      resistance model is shown to be sufficient to capture the effects of both
      intracrystalline and surface diffusion resistances, thus properly linking
      simulation to experimental evidence. This work suggests that future experimental
      work should focus on eliminating/overcoming these surface imperfections, which
      promise an order of magnitude improvement in permeability.

PMID- 27694934
TI  - Translocation and dissemination of commensal bacteria in post-stroke infection.
AB  - Bacterial infection is highly prevalent in patients who have had a stroke.
      Despite the potential contribution of micro-aspiration in post-stroke pneumonia,
      we found that the majority of the microorganisms detected in the patients who
      developed infections after having a stroke were common commensal bacteria that
      normally reside in the intestinal tracts. In a mouse model of ischemic stroke,
      post-stroke infection was only observed in mice that were born and raised in
      specific-pathogen-free facilities; this was not seen in mice that were born and
      raised in germ-free facilities. Using high-throughput 16S rRNA gene amplicon
      sequencing and bioinformatics analyses, we provide evidence demonstrating that
      the source of the bacteria forming the microbial community in the lungs of post
      stroke mice was indeed the host small intestine. Additionally, stroke-induced gut
      barrier permeability and dysfunction preceded the dissemination of orally
      inoculated bacteria to peripheral tissues. This study identifies a novel pathway
      in which stroke promotes the translocation and dissemination of selective strains
      of bacteria that originated from the host gut microbiota.

PMID- 27694936
TI  - Dissecting the regulation rules of cancer-related miRNAs based on network
      analysis.
AB  - miRNAs (microRNAs) are a set of endogenous and small non-coding RNAs which
      specifically induce degradation of target mRNAs or inhibit protein translation to
      control gene expression. Obviously, aberrant miRNA expression in human cells will
      lead to a serious of changes in protein-protein interaction network (PPIN), thus
      to activate or inactivate some pathways related to various diseases, especially
      carcinogenesis. In this study, we systematically constructed the miRNA-regulated
      co-expressed protein-protein interaction network (CePPIN) for 17 cancers firstly.
      We investigated the topological parameters and functional annotation for the
      proteins in CePPIN, especially for those miRNA targets. We found that targets
      regulated by more miRNAs tend to play a more important role in the forming
      process of cancers. We further elucidated the miRNA regulation rules in PPIN from
      a more systematical perspective. By GO and KEGG pathway analysis, miRNA targets
      are involved in various cellular processes mostly related to cell cycle, such as
      cell proliferation, growth, differentiation, etc. Through the Pfam
      classification, we found that miRNAs belonging to the same family tend to have
      targets from the same family which displays the synergistic function of these
      miRNAs. Finally, the case study on miR-519d and miR-21-regulated sub-network was
      performed to support our findings.

PMID- 27694938
TI  - Large Fizeau's light-dragging effect in a moving electromagnetically induced
      transparent medium.
AB  - As one of the most influential experiments on the development of modern
      macroscopic theory from Newtonian mechanics to Einstein's special theory of
      relativity, the phenomenon of light dragging in a moving medium has been
      discussed and observed extensively in different types of systems. To have a
      significant dragging effect, the long duration of light travelling in the medium
      is preferred. Here we demonstrate a light-dragging experiment in an
      electromagnetically induced transparent cold atomic ensemble and enhance the
      dragging effect by at least three orders of magnitude compared with the previous
      experiments. With a large enhancement of the dragging effect, we realize an atom
      based velocimeter that has a sensitivity two orders of magnitude higher than the
      velocity width of the atomic medium used. Such a demonstration could pave the way
      for motional sensing using the collective state of atoms in a room temperature
      vapour cell or solid state material.

PMID- 27694937
TI  - Sensing surface mechanical deformation using active probes driven by motor
      proteins.
AB  - Studying mechanical deformation at the surface of soft materials has been
      challenging due to the difficulty in separating surface deformation from the bulk
      elasticity of the materials. Here, we introduce a new approach for studying the
      surface mechanical deformation of a soft material by utilizing a large number of
      self-propelled microprobes driven by motor proteins on the surface of the
      material. Information about the surface mechanical deformation of the soft
      material is obtained through changes in mobility of the microprobes wandering
      across the surface of the soft material. The active microprobes respond to
      mechanical deformation of the surface and readily change their velocity and
      direction depending on the extent and mode of surface deformation. This highly
      parallel and reliable method of sensing mechanical deformation at the surface of
      soft materials is expected to find applications that explore surface mechanics of
      soft materials and consequently would greatly benefit the surface science.

PMID- 27694939
TI  - Attached biofilms and suspended aggregates are distinct microbial lifestyles
      emanating from differing hydraulics.
AB  - Small-scale hydraulics affects microbial behaviour at the cell level1, trophic
      interactions in marine aggregates2 and the physical structure and function of
      stream biofilms3,4. However, it remains unclear how hydraulics, predictably
      changing from small streams to large rivers, impacts the structure and
      biodiversity of complex microbial communities in these ecosystems. Here, we
      present experimental evidence unveiling hydraulics as a hitherto poorly
      recognized control of microbial lifestyle differentiation in fluvial ecosystems.
      Exposing planktonic source communities from stream and floodplain ecosystems to
      different hydraulic environments revealed strong selective hydraulic pressures
      but only minor founder effects on the differentiation of attached biofilms and
      suspended aggregates and their biodiversity dynamics. Key taxa with a coherent
      phylogenetic underpinning drove this differentiation. Only a few resident and
      phylogenetically related taxa formed the backbone of biofilm communities, whereas
      numerous resident taxa characterized aggregate communities. Our findings unveil
      fundamental differences between biofilms and aggregates and build the basis for a
      mechanistic understanding of how hydraulics drives the distribution of microbial
      diversity along the fluvial continuum5-7.

PMID- 27694940
TI  - Organism-like formation of Schistosoma hemozoin and its function suggest a
      mechanism for anti-malarial action of artemisinin.
AB  - The current theories of antimalarial mechanism of artemisinin are inadequate to
      fully explain the observed effects. In our study, "organism-like" formation of
      Schistosoma hemozoin granules by attaching to and utilizing erythrocytes to form
      new ones was observed. This indicates that heme iron is transferred from
      erythrocytes to hemozoin granules during their formation. However, as a disposal
      product of heme detoxification, these granules are not completely expelled from
      the Schistosoma gut, but decomposed again between microvilli in the posterior
      portion of the gut to transfer iron to eggs. Based on the function of iron
      transport supported by our observation of the unique process of Schistosoma
      hemozoin formation, here we propose a new viewpoint of antimalarial mechanism of
      artemisinin, which emphasizes the final outcome, i.e., interference of iron
      utilization in parasites by artemisinin, instead of focusing on the mode of
      interaction between artemisinin and heme or hemozoin. This suggests that
      artemisinin and its endoperoxides derivatives likely hit the Achilles' heel of
      hemozoin-producing and iron-dependent organisms.

PMID- 27694941
TI  - Extracellular IL-33 cytokine, but not endogenous nuclear IL-33, regulates protein
      expression in endothelial cells.
AB  - IL-33 is a nuclear cytokine from the IL-1 family that plays important roles in
      health and disease. Extracellular IL-33 activates a growing number of target
      cells, including group 2 innate lymphoid cells, mast cells and regulatory T
      cells, but it remains unclear whether intracellular nuclear IL-33 has additional
      functions in the nucleus. Here, we used a global proteomic approach based on high
      resolution mass spectrometry to compare the extracellular and intracellular roles
      of IL-33 in primary human endothelial cells, a major source of IL-33 protein in
      human tissues. We found that exogenous extracellular IL-33 cytokine induced
      expression of a distinct set of proteins associated with inflammatory responses
      in endothelial cells. In contrast, knockdown of endogenous nuclear IL-33
      expression using two independent RNA silencing strategies had no reproducible
      effect on the endothelial cell proteome. These results suggest that IL-33 acts as
      a cytokine but not as a nuclear factor regulating gene expression in endothelial
      cells.

PMID- 27694942
TI  - Histone variant H3F3A promotes lung cancer cell migration through intronic
      regulation.
AB  - Although several somatic single nucleotide variations in histone H3.3 have been
      investigated as cancer drivers, other types of aberration have not been well
      studied. Here, we demonstrate that overexpression of H3F3A, encoding H3.3, is
      associated with lung cancer progression and promotes lung cancer cell migration
      by activating metastasis-related genes. H3.3 globally activates gene expression
      through the occupation of intronic regions in lung cancer cells. Moreover, H3.3
      binding regions show characteristics of regulatory DNA elements. We show that
      H3.3 is deposited at a specific intronic region of GPR87, where it modifies the
      chromatin status and directly activates GPR87 transcription. The expression
      levels of H3F3A and GPR87, either alone or in combination, are robust prognostic
      markers for early-stage lung cancer, and may indicate potential for the
      development of treatments involving GPR87 antagonists. In summary, our results
      demonstrate that intronic regulation by H3F3A may be a target for the development
      of novel therapeutic strategies.

PMID- 27694943
TI  - Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell
      transplantation in Sweden, long-term results from all patients treated in 1994
      2009.
AB  - High-dose melphalan and autologous stem cell transplantation (HDM/ASCT) is widely
      used in immunoglobulin light chain (AL) amyloidosis, but the benefit is debated
      mainly because of the high treatment-related mortality (24% in a randomised study
      comparing HDM/ASCT with oral melphalan/dexamethasone). We report here on the long
      term outcome of all patients treated with HDM/ASCT for AL amyloidosis in Sweden
      between 1994 and 2009. Seventy-two patients were treated at eight Swedish
      centres. Median follow-up was 67.5 months. At least partial response (organ or
      haematological) was seen in 64% of the patients. Median overall survival was 98
      months or 8.2 years, with 5-year survival 63.9% and 10-year survival 43.4%. In
      patients with cardiac involvement or multiple organ involvement, survival was
      significantly shorter, median overall survival 49 and 56 months, respectively.
      All mortality within 100 days from ASCT was 12.5% for all patients and 17.2% in
      the patients with cardiac involvement. For patients treated in the earlier time
      period (1994-2001), 100-day mortality was 23.8% compared with 7.8% in the later
      period (2002-2009). In conclusion, long survival times can be achieved in
      patients with AL amyloidosis treated with HDM/ASCT, also in smaller centres.
      Early mortality is high, but with a decreasing trend over time.

PMID- 27694944
TI  - Efficient Synthesis of Ethanol from CH4 and Syngas on a Cu-Co/TiO2 Catalyst Using
      a Stepwise Reactor.
AB  - Ethanol synthesis from CH4 and syngas on a Cu-Co/TiO2 catalyst is studied using
      experiments, density functional theory (DFT) and microkinetic modelling. The
      experimental results indicate that the active sites of ethanol synthesis from CH4
      and syngas are Cu and CoO, over which the ethanol selectivity is approximately
      98.30% in a continuous stepwise reactor. DFT and microkinetic modelling results
      show that *CH3 is the most abundant species and can be formed from *CH4
      dehydrogenation or through the process of *CO hydrogenation. Next, the insertion
      of *CO into *CH3 forms *CH3CO. Finally, ethanol is formed through *CH3CO and
      *CH3COH hydrogenation. According to our results, small particles of metallic Cu
      and CoO as well as a strongly synergistic effect between metallic Cu and CoO are
      beneficial for ethanol synthesis from CH4 and syngas on a Cu-Co/TiO2 catalyst.

PMID- 27694945
TI  - Genomic prediction contributing to a promising global strategy to turbocharge
      gene banks.
AB  - The 7.4 million plant accessions in gene banks are largely underutilized due to
      various resource constraints, but current genomic and analytic technologies are
      enabling us to mine this natural heritage. Here we report a proof-of-concept
      study to integrate genomic prediction into a broad germplasm evaluation process.
      First, a set of 962 biomass sorghum accessions were chosen as a reference set by
      germplasm curators. With high throughput genotyping-by-sequencing (GBS), we
      genetically characterized this reference set with 340,496 single nucleotide
      polymorphisms (SNPs). A set of 299 accessions was selected as the training set to
      represent the overall diversity of the reference set, and we phenotypically
      characterized the training set for biomass yield and other related traits. Cross
      validation with multiple analytical methods using the data of this training set
      indicated high prediction accuracy for biomass yield. Empirical experiments with
      a 200-accession validation set chosen from the reference set confirmed high
      prediction accuracy. The potential to apply the prediction model to broader
      genetic contexts was also examined with an independent population. Detailed
      analyses on prediction reliability provided new insights into strategy
      optimization. The success of this project illustrates that a global, cost
      effective strategy may be designed to assess the vast amount of valuable
      germplasm archived in 1,750 gene banks.

PMID- 27694946
TI  - A proteinaceous organic matrix regulates carbonate mineral production in the
      marine teleost intestine.
AB  - Marine teleost fish produce CaCO3 in their intestine as part of their
      osmoregulatory strategy. This precipitation is critical for rehydration and
      survival of the largest vertebrate group on earth, yet the molecular mechanisms
      that regulate this reaction are unknown. Here, we isolate and characterize an
      organic matrix associated with the intestinal precipitates produced by Gulf
      toadfish (Opsanus beta). Toadfish precipitates were purified using two different
      methods, and the associated organic matrix was extracted. Greater than 150
      proteins were identified in the isolated matrix by mass spectrometry and
      subsequent database searching using an O. beta transcriptomic sequence library
      produced here. Many of the identified proteins were enriched in the matrix
      compared to the intestinal fluid, and three showed no substantial homology to any
      previously characterized protein in the NCBI database. To test the functionality
      of the isolated matrix, a micro-modified in vitro calcification assay was
      designed, which revealed that low concentrations of isolated matrix substantially
      promoted CaCO3 production, where high concentrations showed an inhibitory effect.
      High concentrations of matrix also decreased the incorporation of magnesium into
      the forming mineral, potentially providing an explanation for the variability in
      magnesium content observed in precipitates produced by different fish species.

PMID- 27694948
TI  - Changes in litter quality induced by nutrient addition alter litter decomposition
      in an alpine meadow on the Qinghai-Tibet Plateau.
AB  - The effects of nitrogen (N) and phosphorus (P) addition on litter decomposition
      are poorly understood in Tibetan alpine meadows. Leaf litter was collected from
      plots within a factorial N * P addition experiment and allowed to decompose over
      708 days in an unfertilized plot to determine the effects of N and/or P addition
      on litter decomposition. Results showed that nutrient addition significantly
      affected initial P and P-related biochemical properties of litter from all four
      species. However, the responses of litter N and N-related biochemical properties
      to nutrient addition were quite species-specific. Litter C decomposition and N
      release were species-specific. However, N and P addition significantly affected
      litter P release. Ratios of Hemicellulose + Cellulose to N and P were
      significantly related to litter C decomposition; C:N ratio was a determinant of
      litter N release; and C:P and (Hemicellulose + Cellulose):P controlled litter P
      release. Overall, litter C decomposition was controlled by litter quality of
      different plant species, and strongly affected by P addition. Increasing N
      availability is likely to affect litter C decomposition more indirectly by
      shifting plant species composition than directly by improving litter quality, and
      may accelerate N and P cycles, but shift the ecosystem to P limitation.

PMID- 27694947
TI  - Organization of olfactory centres in the malaria mosquito Anopheles gambiae.
AB  - Mosquitoes are vectors for multiple infectious human diseases and use a variety
      of sensory cues (olfactory, temperature, humidity and visual) to locate a human
      host. A comprehensive understanding of the circuitry underlying sensory
      signalling in the mosquito brain is lacking. Here we used the Q-system of binary
      gene expression to develop transgenic lines of Anopheles gambiae in which
      olfactory receptor neurons expressing the odorant receptor co-receptor (Orco)
      gene are labelled with GFP. These neurons project from the antennae and maxillary
      palps to the antennal lobe (AL) and from the labella on the proboscis to the
      suboesophageal zone (SEZ), suggesting integration of olfactory and gustatory
      signals occurs in this brain region. We present detailed anatomical maps of
      olfactory innervations in the AL and the SEZ, identifying glomeruli that may
      respond to human body odours or carbon dioxide. Our results pave the way for
      anatomical and functional neurogenetic studies of sensory processing in
      mosquitoes.

PMID- 27694949
TI  - A quorum-sensing signal promotes host tolerance training through HDAC1-mediated
      epigenetic reprogramming.
AB  - The mechanisms by which pathogens evade elimination without affecting host
      fitness are not well understood. For the pathogen Pseudomonas aeruginosa, this
      evasion appears to be triggered by excretion of the quorum-sensing molecule 2
      aminoacetophenone, which dampens host immune responses and modulates host
      metabolism, thereby enabling the bacteria to persist at a high burden level.
      Here, we examined how 2-aminoacetophenone trains host tissues to become tolerant
      to a high bacterial burden, without compromising host fitness. We found that 2
      aminoacetophenone regulates histone deacetylase 1 expression and activity,
      resulting in hypo-acetylation of lysine 18 of histone H3 at pro-inflammatory
      cytokine loci. Specifically, 2-aminoacetophenone induced reprogramming of immune
      cells occurs via alterations in histone acetylation of immune cytokines in vivo
      and in vitro. This host epigenetic reprograming, which was maintained for up to 7
      days, dampened host responses to subsequent exposure to 2-aminoacetophenone or
      other unrelated pathogen-associated molecules. The process was found to involve a
      distinct molecular mechanism of host chromatin regulation. Inhibition of histone
      deacetylase 1 prevented the immunomodulatory effects of 2-aminoacetophenone.
      These observations provide the first mechanistic example of a quorum-sensing
      molecule regulating a host epigenome to enable tolerance of infection. These
      insights have enormous potential for developing preventive treatments against
      bacterial infections.

PMID- 27694950
TI  - Multi-Pass Adaptive Voting for Nuclei Detection in Histopathological Images.
AB  - Nuclei detection is often a critical initial step in the development of computer
      aided diagnosis and prognosis schemes in the context of digital pathology images.
      While over the last few years, a number of nuclei detection methods have been
      proposed, most of these approaches make idealistic assumptions about the staining
      quality of the tissue. In this paper, we present a new Multi-Pass Adaptive Voting
      (MPAV) for nuclei detection which is specifically geared towards images with poor
      quality staining and noise on account of tissue preparation artifacts. The MPAV
      utilizes the symmetric property of nuclear boundary and adaptively selects
      gradient from edge fragments to perform voting for a potential nucleus location.
      The MPAV was evaluated in three cohorts with different staining methods:
      Hematoxylin &Eosin, CD31 &Hematoxylin, and Ki-67 and where most of the nuclei
      were unevenly and imprecisely stained. Across a total of 47 images and nearly
      17,700 manually labeled nuclei serving as the ground truth, MPAV was able to
      achieve a superior performance, with an area under the precision-recall curve
      (AUC) of 0.73. Additionally, MPAV also outperformed three state-of-the-art nuclei
      detection methods, a single pass voting method, a multi-pass voting method, and a
      deep learning based method.

PMID- 27694951
TI  - Prognostic Significance of Neutrophil to Lymphocyte Ratio in Oncologic Outcomes
      of Cholangiocarcinoma: A Meta-analysis.
AB  - Increasing evidence indicates that the neutrophil to lymphocyte ratio (NLR) is a
      useful biomarker of long-term outcomes in patients with cholangiocarcinoma.
      However, the prognostic role of NLR in patients with cholangiocarcinoma remains
      unclear. Thus, the current meta-analysis was undertaken to clarify the
      correlation between NLR and overall survival (OS) in cholangiocarcinoma, and a
      comprehensive literature research was conducted to understand the association of
      NLR and prognosis of cholangiocarcinoma. The hazard ratio (HR) with 95%
      confidence interval (CI) was used to assess OS. The synthesized HR of 1.449 (95%
      CI: 1.296-1.619, P < 0.001) indicated that a high NLR had an unfavourable effect
      on OS. Overall, this meta-analysis suggested that elevated preoperative NLR is
      associated with poorer rates of survival in cholangiocarcinoma patients.

PMID- 27694952
TI  - The backtracking survey propagation algorithm for solving random K-SAT problems.
AB  - Discrete combinatorial optimization has a central role in many scientific
      disciplines, however, for hard problems we lack linear time algorithms that would
      allow us to solve very large instances. Moreover, it is still unclear what are
      the key features that make a discrete combinatorial optimization problem hard to
      solve. Here we study random K-satisfiability problems with K=3,4, which are known
      to be very hard close to the SAT-UNSAT threshold, where problems stop having
      solutions. We show that the backtracking survey propagation algorithm, in a time
      practically linear in the problem size, is able to find solutions very close to
      the threshold, in a region unreachable by any other algorithm. All solutions
      found have no frozen variables, thus supporting the conjecture that only unfrozen
      solutions can be found in linear time, and that a problem becomes impossible to
      solve in linear time when all solutions contain frozen variables.

PMID- 27694953
TI  - Effective pinning energy landscape perturbations for propagating magnetic domain
      walls.
AB  - The interaction between a magnetic domain wall and a pinning site is explored in
      a planar nanowire using micromagnetics to reveal perturbations of the pinning
      energetics for propagating domain walls. Numerical simulations in the high
      damping 'quasi-static' and low damping 'dynamic' regimes are compared and show
      clear differences in de-pinning fields, indicating that dynamical micromagnetic
      models, which incorporate precessionally limited magnetization processes, are
      needed to understand domain wall pinning. Differences in the micromagnetic domain
      wall structure strongly influence the pinning and show periodic behaviour with
      increasing applied field associated with Walker breakdown. In the propagating
      regime pinning is complicated.

PMID- 27694954
TI  - Inhibition of Rac1 GTPase activity affects porcine oocyte maturation and early
      embryo development.
AB  - Mammalian oocyte asymmetric division relies on the eccentric positioning of the
      spindle, resulting in the polar body formation. Small signaling G protein Rac1 is
      a member of GTPases, which regulates a diverse array of cellular events,
      including the control of cell growth, cytoskeletal reorganization, and the
      activation of protein kinases. However, effects of Rac1 on the porcine oocyte
      maturation and early embryo development are not fully understood. In present
      study we investigated the role of Rac1 in oocyte maturation and embryo cleavage.
      We first found that Rac1 localized at the cortex of the porcine oocytes, and
      disrupting the Rac1 activities by treating with NSC 23766 led to the failure of
      polar body emission. In addition, a majority of treated oocytes exhibited
      abnormal spindle morphology, indicating that Rac1 may involve into porcine oocyte
      spindle formation. This might be due to the regulation of Rac1 on MAPK, since p
      MAPK expression decreased after NSC 23766 treatments. Moreover, we found that the
      position of most meiotic spindles in treated oocytes were away from the cortex,
      indicating the roles of Rac1 on meiotic spindle positioning. Our results also
      showed that inhibition of Rac1 activity caused the failure of early embryo
      development. Therefore, our study showed the critical roles of Rac1 GTPase on
      porcine oocyte maturation and early embryo cleavage.

PMID- 27694955
TI  - Default mode network and frontolimbic gray matter abnormalities in patients with
      borderline personality disorder: A voxel-based meta-analysis.
AB  - Specific frontolimbic abnormalities are hypothesized to underlie the etiology of
      borderline personality disorder (BPD). However, findings from neuroimaging
      studies were inconsistent. In the current study, we aimed to provide a complete
      overview of cerebral microstructural alterations in gray matter (GM) of BPD
      patients. A total of 11 studies were enrolled, comprising 275 BPD patients and
      290 healthy controls (HCs). A meta-analysis was conduct to quantitatively
      estimate regional GM abnormalities in BPD patients using the seed-based d mapping
      (SDM). Meta-regression was also conducted. Compared with HCs, the BPD patients
      exhibited increased GM mainly in bilateral supplementary motor area extending to
      right posterior cingulated cortex (PCC) and bilateral primary motor cortex, right
      middle frontal gyrus (MFG), and the bilateral precuneus extending to bilateral
      PCC. Decreased GM was identified in bilateral middle temporal gyri, right
      inferior frontal gyrus extending to right insular, left hippocampus and left
      superior frontal gyrus extending to left medial orbitofrontal cortex. The mean
      age of BPD patients were found nagativly associated with GM alterations in right
      MFG. Our findings suggested that BPD patients have significantly GM abnormalities
      in the default mode network and frontolimbic circuit. Our results provided
      further evidences in elucidating the underline neural mechanisms of BPD.

PMID- 27694956
TI  - Prediction and evaluation of the lipase inhibitory activities of tea polyphenols
      with 3D-QSAR models.
AB  - The extraordinary hypolipidemic effects of polyphenolic compounds from tea have
      been confirmed in our previous study. To gain compounds with more potent
      activities, using the conformations of the most active compound revealed by
      molecular docking, a 3D-QSAR pancreatic lipase inhibitor model with good
      predictive ability was established and validated by CoMFA and CoMISA methods.
      With good statistical significance in CoMFA (r2cv = 0.622, r2 = 0.956, F =
      261.463, SEE = 0.096) and CoMISA (r2cv = 0.631, r2 = 0.932, F = 75.408, SEE =
      0.212) model, we summarized the structure-activity relationship between
      polyphenolic compounds and pancreatic lipase inhibitory activities and find the
      bulky substituents in R2, R4 and R5, hydrophilic substituents in R1 and electron
      withdrawing groups in R2 are the key factors to enhance the lipase inhibitory
      activities. Under the guidance of the 3D-QSAR results, (2R,3R,2'R,3'R)
      desgalloyloolongtheanin-3,3'-O-digallate (DOTD), a potent lipase inhibitor with
      an IC50 of 0.08 MUg/ml, was obtained from EGCG oxidative polymerization catalyzed
      by crude polyphenol oxidase. Furthermore, DOTD was found to inhibit lipid
      absorption in olive oil-loaded rats, which was related with inhibiting the
      activities of lipase in the intestinal mucosa and contents.

PMID- 27694957
TI  - The site of water stress governs the pattern of ABA synthesis and transport in
      peanut.
AB  - Abscisic acid (ABA) is one of the most important phytohormones involved in stress
      responses in plants. However, knowledge of the effect on ABA distribution and
      transport of water stress at different sites on the plant is limited. In this
      study, water stress imposed on peanut leaves or roots by treatment with PEG 6000
      is termed "leaf stress" or "root stress", respectively. Immunoenzyme localization
      technolony was first used to detect ABA distribution in peanut. Under root
      stress, ABA biosynthesis and distribution level were all more pronounced in root
      than in leaf. However, ABA transport and the ability to induce stomatal closure
      were still better in leaf than in root during root stress; However, ABA
      biosynthesis initially increased in leaf, then rapidly accumulated in the
      vascular cambium of leaves and induced stomatal closure under leaf stress; ABA
      produced in root tissues was also transported to leaf tissues to maintain
      stomatal closure. The vascular system was involved in the coordination and
      integration of this complex regulatory mechanism for ABA signal accumulation.
      Water stress subject to root or leaf results in different of ABA biosynthesis and
      transport ability that trigger stoma close in peanut.

PMID- 27694958
TI  - Reference-based phasing using the Haplotype Reference Consortium panel.
AB  - Haplotype phasing is a fundamental problem in medical and population genetics.
      Phasing is generally performed via statistical phasing in a genotyped cohort, an
      approach that can yield high accuracy in very large cohorts but attains lower
      accuracy in smaller cohorts. Here we instead explore the paradigm of reference
      based phasing. We introduce a new phasing algorithm, Eagle2, that attains high
      accuracy across a broad range of cohort sizes by efficiently leveraging
      information from large external reference panels (such as the Haplotype Reference
      Consortium; HRC) using a new data structure based on the positional Burrows
      Wheeler transform. We demonstrate that Eagle2 attains a ~20* speedup and ~10%
      increase in accuracy compared to reference-based phasing using SHAPEIT2. On
      European-ancestry samples, Eagle2 with the HRC panel achieves >2* the accuracy of
      1000 Genomes-based phasing. Eagle2 is open source and freely available for HRC
      based phasing via the Sanger Imputation Service and the Michigan Imputation
      Server.

PMID- 27694959
TI  - The effect of host genetics on the gut microbiome.
AB  - The gut microbiome is affected by multiple factors, including genetics. In this
      study, we assessed the influence of host genetics on microbial species, pathways
      and gene ontology categories, on the basis of metagenomic sequencing in 1,514
      subjects. In a genome-wide analysis, we identified associations of 9 loci with
      microbial taxonomies and 33 loci with microbial pathways and gene ontology terms
      at P < 5 * 10-8. Additionally, in a targeted analysis of regions involved in
      complex diseases, innate and adaptive immunity, or food preferences, 32 loci were
      identified at the suggestive level of P < 5 * 10-6. Most of our reported
      associations are new, including genome-wide significance for the C-type lectin
      molecules CLEC4F-CD207 at 2p13.3 and CLEC4A-FAM90A1 at 12p13. We also identified
      association of a functional LCT SNP with the Bifidobacterium genus (P = 3.45 * 10
      8) and provide evidence of a gene-diet interaction in the regulation of
      Bifidobacterium abundance. Our results demonstrate the importance of
      understanding host-microbe interactions to gain better insight into human health.

PMID- 27694960
TI  - Association of host genome with intestinal microbial composition in a large
      healthy cohort.
AB  - Intestinal microbiota is known to be important in health and disease. Its
      composition is influenced by both environmental and host factors. Few large-scale
      studies have evaluated the association between host genetic variation and the
      composition of microbiota. We recruited a cohort of 1,561 healthy individuals, of
      whom 270 belong in 123 families, and found that almost one-third of fecal
      bacterial taxa were heritable. In addition, we identified 58 SNPs associated with
      the relative abundance of 33 taxa in 1,098 discovery subjects. Among these, four
      loci were replicated in a second cohort of 463 subjects: rs62171178 (nearest gene
      UBR3) associated with Rikenellaceae, rs1394174 (CNTN6) associated with
      Faecalibacterium, rs59846192 (DMRTB1) associated with Lachnospira, and rs28473221
      (SALL3) associated with Eubacterium. After correction for multiple testing, 6 of
      the 58 associations remained significant, one of which replicated. These results
      identify associations between specific genetic variants and the gut microbiome.

PMID- 27694963
TI  - A role for the asexual spores in infection of Fraxinus excelsior by the ash
      dieback fungus Hymenoscyphus fraxineus.
AB  - The invasive pathogen, ash dieback fungus Hymenoscyphus fraxineus, is spreading
      rapidly across Europe. It shows high levels of outcrossing and limited population
      structure, even at the epidemic front. The anamorphic (asexual) form produces
      prolific conidia, thought to function solely as spermatia (male gametes),
      facilitating gene flow between sympatric strains. Here, we show that conidia are
      capable of germination on ash leaves and in vitro, and can infect seedlings via
      leaves or soil. In leaves, germlings form structures resembling fruiting bodies.
      Additionally, H. fraxineus colonises ash debris and grows in soil in the absence
      of ash tissues. We propose an amended life-cycle in which wind-dispersed, insect
      vectored or water-spread conidia infect ash and may sporulate in planta, as well
      as in forest debris. This amplifies inoculum levels of different strains in ash
      stands. In combination with their function as spermatia, conidia thus act to
      maximise gene flow between sympatric strains, including those originally present
      at low inoculum. Such mixing increases evolutionary potential, as well as
      enhancing the likelihood of gene introgression from closely-related strains or
      assimilation of further genetic diversity from parental Asian populations. This
      scenario increases the adaptability of H. fraxineus to new climates and, indeed,
      onto new host species.

PMID- 27694962
TI  - A 3'-end structure in RNA2 of a crinivirus is essential for viral RNA synthesis
      and contributes to replication-associated translation activity.
AB  - The terminal ends in the genome of RNA viruses contain features that regulate
      viral replication and/or translation. We have identified a Y-shaped structure
      (YSS) in the 3' terminal regions of the bipartite genome of Lettuce chlorosis
      virus (LCV), a member in the genus Crinivirus (family Closteroviridae). The YSS
      is the first in this family of viruses to be determined using Selective 2'
      Hydroxyl Acylation Analyzed by Primer Extension (SHAPE). Using luciferase
      constructs/replicons, in vivo and in vitro assays showed that the 5' and YSS
      containing 3' terminal regions of LCV RNA1 supported translation activity. In
      contrast, similar regions from LCV RNA2, including those upstream of the YSS, did
      not. LCV RNA2 mutants with nucleotide deletions or replacements that affected the
      YSS were replication deficient. In addition, the YSS of LCV RNA1 and RNA2 were
      interchangeable without affecting viral RNA synthesis. Translation and
      significant replication were observed for specific LCV RNA2 replicons only in the
      presence of LCV RNA1, but both processes were impaired when the YSS and/or its
      upstream region were incomplete or altered. These results are evidence that the
      YSS is essential to the viral replication machinery, and contributes to
      replication enhancement and replication-associated translation activity in the
      RNA2 replicons.

PMID- 27694964
TI  - Potassium Management for Improving Growth and Grain Yield of Maize (Zea mays L.)
      under Moisture Stress Condition.
AB  - Potassium (K) fertilizer management is beneficial for improving growth, yield and
      yield components of field crops under moisture stress condition in semiarid
      climates. Field experiments were conducted to study the response of maize (Zea
      mays L., cv. Azam) to foliar and soil applied K during summer 2013 and 2014. The
      experiments were carried out at the Agronomy Research Farm of The University of
      Agriculture Peshawar, Northwest Pakistan under limited irrigation (moisture
      stress) condition. It was concluded from the results that application of foliar K
      at the rate of 1-3% and foliar Zn at the rate of 0.1-0.2% was more beneficial in
      terms of better growth, higher yield and yield components of maize under moisture
      stress condition. Early spray (vegetative stage) resulted in better growth and
      higher yield than late spray (reproductive stage). Soil K treated plots (rest)
      plots performed better than control (K not applied) in terms of improved growth,
      higher yield and yield components of maize crop. The results further demonstrated
      that increasing the rate of soil applied K up to 90 kg P ha-1 in two equal splits
      (50% each at sowing and knee height) improve growth and maize productivity under
      semiarid climates.

PMID- 27694961
TI  - Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and
      cause periventricular nodular heterotopia.
AB  - Neurodevelopmental disorders with periventricular nodular heterotopia (PNH) are
      etiologically heterogeneous, and their genetic causes remain in many cases
      unknown. Here we show that missense mutations in NEDD4L mapping to the HECT
      domain of the encoded E3 ubiquitin ligase lead to PNH associated with toe
      syndactyly, cleft palate and neurodevelopmental delay. Cellular and expression
      data showed sensitivity of PNH-associated mutants to proteasome degradation.
      Moreover, an in utero electroporation approach showed that PNH-related mutants
      and excess wild-type NEDD4L affect neurogenesis, neuronal positioning and
      terminal translocation. Further investigations, including rapamycin-based
      experiments, found differential deregulation of pathways involved. Excess wild
      type NEDD4L leads to disruption of Dab1 and mTORC1 pathways, while PNH-related
      mutations are associated with deregulation of mTORC1 and AKT activities.
      Altogether, these data provide insights into the critical role of NEDD4L in the
      regulation of mTOR pathways and their contributions in cortical development.

PMID- 27694965
TI  - Coronary artery calcium is associated with cortical thinning in cognitively
      normal individuals.
AB  - To evaluate the association between coronary artery calcium (CAC) and cortical
      thickness in a large sample of cognitively normal individuals, with special
      emphasis in determining if the association thickness has regional brain
      specificity and if it is mediated by white matter hyperintensities (WMH). A total
      of 512 participants were included in this study. CAC scores were assessed by
      multi-detector computed tomography. Cortical thickness was measured using a
      surface-based method. Linear mixed models were used to assess the association
      between CAC scores and cortical thickness. In fully adjusted models, increased
      CAC scores were associated with cortical thinning across several brain regions,
      which generally overlapped with the distribution of default mode network. The
      association between CAC scores and cortical thickness was significantly stronger
      in participants with moderate or severe WMH compared to those with none or mild
      WMH, even though CAC scores were not associated with WMH. In cognitively normal
      adults, CAC was associated with cortical thinning in areas related to cognitive
      function. This association was evident after adjusting for multiple coronary
      artery disease risk factors and for WMH, suggesting that CAC may be more closely
      related to Alzheimer's Disease-type disease rather than to cerebral small vessel
      disease.

PMID- 27694966
TI  - High sensitivity of gold nanoparticles co-doped with Gd2O3 mesoporous silica
      nanocomposite to nasopharyngeal carcinoma cells.
AB  - Nanoprobes for combined optical and magnetic resonance imaging have tremendous
      potential in early cancer diagnosis. Gold nanoparticles (AuNPs) co-doped with
      Gd2O3 mesoporous silica nanocomposite (Au/Gd@MCM-41) can produce pronounced
      contrast enhancement for T1 weighted image in magnetic resonance imaging (MRI).
      Here, we show the remarkably high sensitivity of Au/Gd@MCM-41 to the human poorly
      differentiated nasopharyngeal carcinoma (NPC) cell line (CNE-2) using
      fluorescence lifetime imaging (FLIM). The upconversion luminescences from CNE-2
      and the normal nasopharyngeal (NP) cells (NP69) after uptake of Au/Gd@MCM-41 show
      the characteristic of two-photon-induced-radiative recombination of the AuNPs.
      The presence of the Gd3+ ion induces a much shorter luminescence lifetime in CNE
      2 cells. The interaction between AuNPs and Gd3+ ion clearly enhances the optical
      sensitivity of Au/Gd@MCM-41 to CNE-2. Furthermore, the difference in the
      autofluorescence between CNE-2 and NP69 cells can be efficiently demonstrated by
      the emission lifetimes of Au/Gd@MCM-41 through the Forster energy transfers from
      the endogenous fluorophores to AuNPs. The results suggest that Au/Gd@MCM-41 may
      impart high optical resolution for the FLIM imaging that differentiates normal
      and high-grade precancers.

PMID- 27694967
TI  - Regionalization of Habitat Suitability of Masson's Pine based on geographic
      information system and Fuzzy Matter-Element Model.
AB  - Pine needles have been widely used in the development of anti-hypertensive and
      anti-hyperlipidemic agents and health food. However, the widespread distribution
      of this tree poses great obstacles to the quality control and efficacy
      evaluation. To facilitate the effective and rational exploitation of Masson's
      pine (Pinus massoniana Lamb), as well as ensure effective development of Masson's
      pine needles as a medicinal agent, we investigated the spatial distribution of
      habitat suitability and evaluated the optimal ranges of ecological factors of P.
      massoniana with 280 samples collected from 12 provinces in China through the
      evaluation of four constituents known to be effective medicinally. The results of
      habitat suitability evaluation were also verified by Root Mean Square Error
      (RMSE). Finally, five ecological factors were chosen in the establishment of a
      habitat suitability evaluation system. The most suitable areas for P. massoniana
      growth were mainly concentrated in the middle and lower reaches of the Yangtze
      River basin, such as Sichuan, Guizhou, and Jiangxi provinces, while the best
      quality needles were from Guizhou, Sichuan, and the junction area of Chongqing,
      Hunan, and Hubei provinces. This information revealed that suitable areas for
      effective constituent accumulation of Masson's pine needles accounted for only
      7.41% of its distribution area.

PMID- 27694968
TI  - Transport of cerium oxide nanoparticles in saturated silica media: influences of
      operational parameters and aqueous chemical conditions.
AB  - This paper aimed to investigate the influences of operational parameters and
      aqueous chemical conditions on transport behaviors of cerium oxides nanoparticles
      (CeO2-NPs) in saturated silica media. Results indicated that increasing rates of
      attachment efficiency (alpha) were related with cationic types, and critical
      deposition concentration (CDC) for divalent cation (Ca2+ and Mg2+) were more than
      31-fold of that for monovalent cation (Na+ and K+). Increase or reduction of
      electrolyte pH could both promote the mobility of CeO2-NPs in glass beads, while
      influence was more evident at alkaline conditions. alpha increased linearly with
      NPs concentrations, while decreased linearly with flow velocity in the column,
      and effects were related with electrolyte contents. Presence of surfactants could
      sharply decreased alpha, and SDS was more effective to facilitate CeO2-NPs
      transport than Triton X-100. With DOMs concentrations increasing, alpha firstly
      kept constant, then sharply declined, and finally reduced very slowly. The
      influence of DOMs on NPs deposition was in order of SA > HA > TA >  BSA. Overall,
      this study revealed that aqueous chemical conditions was crucial to NPs transport
      in porous media, and would provide significant information for our understanding
      on the fate and transport of nanoparticles in natural environment.

PMID- 27694969
TI  - Neural Correlates of Deficits in Humor Appreciation in Gelotophobics.
AB  - Gelotophobics have social deficits in the form of relative humorlessness and
      heightened sensitivity to aggressive humor; however, little is known about the
      neural reward mechanisms for this group. The present study attempted to identify
      the neural substrates of responses to hostile and non-hostile jokes in
      gelotophobics and non-gelotophobics. Gelotophobics showed greater activation than
      did non-gelotophobics in the dorsal corticostriatal system, which comprises the
      dorsolateral prefrontal cortex and dorsal striatum, suggesting a higher degree of
      voluntary top-down cognitive control of emotion. As expected, gelotophobics
      showed less activation in the ventral mesocorticolimbic system (MCL) in response
      to both hostile and non-hostile jokes, suggesting a relative deficit in the
      reward system. Conversely, non-gelotophobics displayed greater activation than
      gelotophobics did in the MCL system, particularly for non-hostile jokes, which
      suggests a more robust bottom-up emotional response. In response to non-hostile
      jokes, non-gelotophobics showed greater activation in the ventral MCL reward
      system, which comprises the midbrain, amygdalae, nucleus accumbens, ventral
      anterior cingulate cortex, and insula. Psychophysiological interaction analyses
      further showed that gelotophobics exhibited diminished MCL activation in response
      to hostile jokes. These group differences may have important implications for our
      understanding of the neural correlates of social motivation and humor
      appreciation.

PMID- 27694972
TI  - Erratum: Brain-mechanistic responses to varying difficulty levels of approximate
      solutions to arithmetic problems.

PMID- 27694970
TI  - Glycine triggers a non-ionotropic activity of GluN2A-containing NMDA receptors to
      confer neuroprotection.
AB  - Ionotropic activation of NMDA receptors (NMDARs) requires agonist glutamate and
      co-agonist glycine. Here we show that glycine enhances the activation of cell
      survival-promoting kinase Akt in cultured cortical neurons in which both the
      channel activity of NMDARs and the glycine receptors are pre-inhibited. The
      effect of glycine is reduced by shRNA-mediated knockdown of GluN2A subunit
      containing NMDARs (GluN2ARs), suggesting that a non-ionotropic activity of
      GluN2ARs mediates glycine-induced Akt activation. In support of this finding,
      glycine enhances Akt activation in HEK293 cells over-expressing GluN2ARs. The
      effect of glycine on Akt activation is sensitive to the antagonist of glycine
      GluN1 binding site. As a functional consequence, glycine protects against
      excitotoxicity-induced neuronal death through the non-ionotropic activity of
      GluN2ARs and the neuroprotective effect is attenuated by Akt inhibition. Thus,
      this study reveals an unexpected role of glycine in eliciting a non-ionotropic
      activity of GluN2ARs to confer neuroprotection via Akt activation.

PMID- 27694971
TI  - The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is
      shaped by strong epistatic interactions.
AB  - Colistin is an antimicrobial peptide that has become the only remaining
      alternative for the treatment of multidrug-resistant Gram-negative bacterial
      infections, but little is known of how clinical levels of colistin resistance
      evolve. We use in vitro experimental evolution and whole-genome sequencing of
      colistin-resistant Pseudomonas aeruginosa isolates from cystic fibrosis patients
      to reconstruct the molecular evolutionary pathways open for high-level colistin
      resistance. We show that the evolution of resistance is a complex, multistep
      process that requires mutation in at least five independent loci that
      synergistically create the phenotype. Strong intergenic epistasis limits the
      number of possible evolutionary pathways to resistance. Mutations in
      transcriptional regulators are essential for resistance evolution and function as
      nodes that potentiate further evolution towards higher resistance by
      functionalizing and increasing the effect of the other mutations. These results
      add to our understanding of clinical antimicrobial peptide resistance and the
      prediction of resistance evolution.

PMID- 27694973
TI  - Real-space observation of magnetic excitations and avalanche behavior in
      artificial quasicrystal lattices.
AB  - Artificial spin ice lattices have emerged as model systems for studying magnetic
      frustration in recent years. Most work to date has looked at periodic artificial
      spin ice lattices. In this paper, we observe frustration effects in quasicrystal
      artificial spin ice lattices that lack translational symmetry and contain
      vertices with different numbers of interacting elements. We find that as the
      lattice state changes following demagnetizing and annealing, specific vertex
      motifs retain low-energy configurations, which excites other motifs into higher
      energy configurations. Additionally, we find that unlike the magnetization
      reversal process for periodic artificial spin ice lattices, which occurs through
      1D avalanches, quasicrystal lattices undergo reversal through a dendritic 2D
      avalanche mechanism.

PMID- 27694974
TI  - Antidepressant indatraline induces autophagy and inhibits restenosis via
      suppression of mTOR/S6 kinase signaling pathway.
AB  - Indatraline is an antidepressive agent and a non-selective monoamine transporter
      inhibitor that blocks the reuptake of neurotransmitters (dopamine, serotonin, and
      norepinephrine). In this study, we report that indatraline induces autophagy via
      the suppression of mTOR/S6 kinase signaling. Autophagy induction was examined by
      a cell-based high content screening system using LysoTracker, which was followed
      by monodansylcadaverine staining and transmission electron microscope
      observation. Indatraline increased the number of EGFP-LC3 cells expressing
      autophagosomes in the cytoplasm. Conversion of LC3 was further validated by
      immunoblotting. Indatraline induced autophagy by affecting the AMPK/mTOR/S6K
      signaling axis and had no influence on the PI3K/AKT/ERK signaling. Moreover,
      indatraline induced autophagy in smooth muscle cells (SMCs); further, it
      exhibited therapeutic potential for restenosis by inhibiting SMC accumulation in
      a rat restenosis model. These results provide new insights into the role of
      monoamine transporters in autophagy regulation and identify indatraline as a
      novel agent for inducing autophagy.

PMID- 27694975
TI  - Projection-type see-through holographic three-dimensional display.
AB  - Owing to the limited spatio-temporal resolution of display devices, dynamic
      holographic three-dimensional displays suffer from a critical trade-off between
      the display size and the visual angle. Here we show a projection-type holographic
      three-dimensional display, in which a digitally designed holographic optical
      element and a digital holographic projection technique are combined to increase
      both factors at the same time. In the experiment, the enlarged holographic image,
      which is twice as large as the original display device, projected on the screen
      of the digitally designed holographic optical element was concentrated at the
      target observation area so as to increase the visual angle, which is six times as
      large as that for a general holographic display. Because the display size and the
      visual angle can be designed independently, the proposed system will accelerate
      the adoption of holographic three-dimensional displays in industrial
      applications, such as digital signage, in-car head-up displays, smart-glasses and
      head-mounted displays.

PMID- 27694976
TI  - A universal test for gravitational decoherence.
AB  - Quantum mechanics and the theory of gravity are presently not compatible. A
      particular question is whether gravity causes decoherence. Several models for
      gravitational decoherence have been proposed, not all of which can be described
      quantum mechanically. Since quantum mechanics may need to be modified, one may
      question the use of quantum mechanics as a calculational tool to draw conclusions
      from the data of experiments concerning gravity. Here we propose a general method
      to estimate gravitational decoherence in an experiment that allows us to draw
      conclusions in any physical theory where the no-signalling principle holds, even
      if quantum mechanics needs to be modified. As an example, we propose a concrete
      experiment using optomechanics. Our work raises the interesting question whether
      other properties of nature could similarly be established from experimental
      observations alone-that is, without already having a rather well-formed theory of
      nature to make sense of experimental data.

PMID- 27694977
TI  - Modification of plant cell wall structure accompanied by enhancement of
      saccharification efficiency using a chemical, lasalocid sodium.
AB  - The cell wall is one major determinant of plant cell morphology, and is an
      attractive bioresource. Here, we report a novel strategy to modify plant cell
      wall property by small molecules. Lasalocid sodium (LS) was isolated by chemical
      screening to identify molecules that affect the cell morphology of tobacco BY-2
      cells. LS treatment led to an increase in cell wall thickness, whilst the
      quantity and sugar composition of the cell wall remained unchanged in BY-2 cells.
      The chemical also disordered the cellular arrangement of hypocotyls of
      Arabidopsis plants, resulting in a decrease in hypocotyl length. LS treatment
      enhanced enzymatic saccharification efficiency in both BY-2 cells and Arabidopsis
      plants. Microarray analysis on Arabidopsis showed that exposure to LS upregulated
      type III peroxidase genes, of which some are involved in lignin biogenesis, and
      jasmonic acid response genes, and phloroglucinol staining supported the
      activation of lignification by the LS treatment. As jasmonic acid-mediated
      lignification is a typical reaction to cell wall damage, it is possible that LS
      induces cell wall loosening, which can trigger cell wall damage response. Thus,
      LS is a unique chemical for modification of cell wall and morphology through
      changes in cell wall architecture.

PMID- 27694980
TI  - Podocyte biology: Dynamic control of actin remodelling.

PMID- 27694978
TI  - Precision medicine from the renal cancer genome.
AB  - Genomics is revolutionizing our understanding of the molecular basis of renal
      cell carcinoma (RCC). The advent of unbiased genome-wide association studies has
      led to the discovery of previously unrecognized genetic predisposing factors that
      impact an individual's risk of developing RCC. Moreover, large-scale
      investigations of somatic alterations of the genomic and transcriptomic
      landscapes in tumours using next-generation sequencing technology have revealed
      new information on the molecular pathways that are characteristically disrupted
      in various RCC subtypes. Sequencing studies have revealed that epigenetic
      machinery and chromatin remodelling complexes are disrupted in >80% of clear cell
      RCC tumours, the most common form of the disease. The growing knowledge of
      subtype-specific molecular abnormalities arising from genomics has opened new
      avenues towards the development of molecular diagnostics for RCC subtypes, and
      for the rational design of therapeutic approaches tailored to patients based on
      the molecular profiles of their tumours. Genomic studies have also pinpointed a
      possible role of environmental exposure to aristolochic acid, a nephrotoxin, in
      the genesis of the disease in some regions of central Europe. In this Review, we
      discuss the impact of genomics in identifying the genes and environmental
      exposures involved in disease susceptibility, and in discovering the molecular
      pathways that are disrupted somatically in different RCC subtypes. Further, we
      explore the possibilities provided by this genomic knowledge in providing a
      precision medicine approach for diagnosing and treating RCC.

PMID- 27694979
TI  - The importance of total kidney volume in evaluating progression of polycystic
      kidney disease.
AB  - The rate at which autosomal dominant polycystic kidney disease (ADPKD) progresses
      to end-stage renal disease varies widely and is determined by genetic and non
      genetic factors. The ability to determine the prognosis of children and young
      adults with ADPKD is important for the effective life-long management of the
      disease and to enable the efficacy of emerging therapies to be determined. Total
      kidney volume (TKV) reflects the sum volume of hundreds of individual cysts with
      potentially devastating effects on renal function. The sequential measurement of
      TKV has been advanced as a dynamic biomarker of disease progression, yet doubt
      remains among nephrologists and regulatory agencies as to its usefulness. Here,
      we review the mechanisms that lead to an increase in TKV in ADPKD, and examine
      the evidence supporting the conclusion that TKV provides a metric of disease
      progression that can be used to assess the efficacy of potential therapeutic
      regimens in children and adults with ADPKD. Moreover, we propose that TKV can be
      used to monitor treatment efficacy in patients with normal levels of renal
      function, before the pathologic processes of ADPKD cause extensive fibrosis and
      irreversible loss of functioning renal tissue.

PMID- 27694981
TI  - The optical frequency comb fibre spectrometer.
AB  - Optical frequency comb sources provide thousands of precise and accurate optical
      lines in a single device enabling the broadband and high-speed detection required
      in many applications. A main challenge is to parallelize the detection over the
      widest possible band while bringing the resolution to the single comb-line level.
      Here we propose a solution based on the combination of a frequency comb source
      and a fibre spectrometer, exploiting all-fibre technology. Our system allows for
      simultaneous measurement of 500 isolated comb lines over a span of 0.12 THz in a
      single acquisition; arbitrarily larger span are demonstrated (3,500 comb lines
      over 0.85 THz) by doing sequential acquisitions. The potential for precision
      measurements is proved by spectroscopy of acetylene at 1.53 MUm. Being based on
      all-fibre technology, our system is inherently low-cost, lightweight and may lead
      to the development of a new class of broadband high-resolution spectrometers.

PMID- 27694982
TI  - Genome-wide association analysis identifies genetic loci associated with
      resistance to multiple antimalarials in Plasmodium falciparum from China-Myanmar
      border.
AB  - Drug resistance has emerged as one of the greatest challenges facing malaria
      control. The recent emergence of resistance to artemisinin (ART) and its partner
      drugs in ART-based combination therapies (ACT) is threatening the efficacy of
      this front-line regimen for treating Plasmodium falciparum parasites. Thus, an
      understanding of the molecular mechanisms that underlie the resistance to ART and
      the partner drugs has become a high priority for resistance containment and
      malaria management. Using genome-wide association studies, we investigated the
      associations of genome-wide single nucleotide polymorphisms with in vitro
      sensitivities to 10 commonly used antimalarial drugs in 94 P. falciparum isolates
      from the China-Myanmar border area, a region with the longest history of ART
      usage. We identified several loci associated with various drugs, including those
      containing pfcrt and pfdhfr. Of particular interest is a locus on chromosome 10
      containing the autophagy-related protein 18 (ATG18) associated with decreased
      sensitivities to dihydroartemisinin, artemether and piperaquine - an ACT partner
      drug in this area. ATG18 is a phosphatidylinositol-3-phosphate binding protein
      essential for autophagy and recently identified as a potential ART target.
      Further investigations on the ATG18 and genes at the chromosome 10 locus may
      provide an important lead for a connection between ART resistance and autophagy.

PMID- 27694983
TI  - Disruption of phenylalanine hydroxylase reduces adult lifespan and fecundity, and
      impairs embryonic development in parthenogenetic pea aphids.
AB  - Phenylalanine hydroxylase (PAH) is a key tyrosine-biosynthetic enzyme involved in
      neurological and melanin-associated physiological processes. Despite extensive
      investigations in holometabolous insects, a PAH contribution to insect embryonic
      development has never been demonstrated. Here, we have characterized, for the
      first time, the PAH gene in a hemimetabolous insect, the aphid Acyrthosiphon
      pisum. Phylogenetic and sequence analyses confirmed that ApPAH is closely related
      to metazoan PAH, exhibiting the typical ACT regulatory and catalytic domains.
      Temporal expression patterns suggest that ApPAH has an important role in aphid
      developmental physiology, its mRNA levels peaking at the end of embryonic
      development. We used parental dsApPAH treatment to generate successful knockdown
      in aphid embryos and to study its developmental role. ApPAH inactivation shortens
      the adult aphid lifespan and considerably affects fecundity by diminishing the
      number of nymphs laid and impairing embryonic development, with newborn nymphs
      exhibiting severe morphological defects. Using single nymph HPLC analyses, we
      demonstrated a significant tyrosine deficiency and a consistent accumulation of
      the upstream tyrosine precursor, phenylalanine, in defective nymphs, thus
      confirming the RNAi-mediated disruption of PAH activity. This study provides
      first insights into the role of PAH in hemimetabolous insects and demonstrates
      that this metabolic gene is essential for insect embryonic development.

PMID- 27694984
TI  - Interplay between transglutaminases and heparan sulphate in progressive renal
      scarring.
AB  - Transglutaminase-2 (TG2) is a new anti-fibrotic target for chronic kidney
      disease, for its role in altering the extracellular homeostatic balance leading
      to excessive build-up of matrix in kidney. However, there is no confirmation that
      TG2 is the only transglutaminase involved, neither there are strategies to
      control its action specifically over that of the conserved family-members. In
      this study, we have profiled transglutaminase isozymes in the rat subtotal
      nephrectomy (SNx) model of progressive renal scarring. All transglutaminases
      increased post-SNx peaking at loss of renal function but TG2 was the predominant
      enzyme. Upon SNx, extracellular TG2 deposited in the tubulointerstitium and peri
      glomerulus via binding to heparan sulphate (HS) chains of proteoglycans and co
      associated with syndecan-4. Extracellular TG2 was sufficient to activate
      transforming growth factor-beta1 in tubular epithelial cells, and this process
      occurred in a HS-dependent way, in keeping with TG2-affinity for HS. Analysis of
      heparin binding of the main transglutaminases revealed that although the
      interaction between TG1 and HS is strong, the conformational heparin binding site
      of TG2 is not conserved, suggesting that TG2 has a unique interaction with HS
      within the family. Our data provides a rationale for a novel anti-fibrotic
      strategy specifically targeting the conformation-dependent TG2-epitope
      interacting with HS.

PMID- 27694987
TI  - Novel optical gyroscope: proof of principle demonstration and future scope.
AB  - We report the first proof-of-principle demonstration of the resonant optical
      gyroscope with reflector that we have recently proposed. The device is very
      different from traditional optical gyroscopes since it uses the inherent coupling
      between the clockwise and counterclockwise propagating waves to sense the
      rotation. Our demonstration confirms our theoretical analysis and simulations. We
      also demonstrate a novel method of biasing the gyroscope using orthogonal
      polarization states. The simplicity of the structure and the readout method, the
      theoretically predicted high sensitivities (better than 0.001 deg/hr), and the
      possibility of further performance enhancement using a related laser based active
      device, all have immense potential for attracting fresh research and
      technological initiatives.

PMID- 27694985
TI  - 3D bioprinting matrices with controlled pore structure and release function guide
      in vitro self-organization of sweat gland.
AB  - 3D bioprinting matrices are novel platforms for tissue regeneration. Tissue self
      organization is a critical process during regeneration that implies the features
      of organogenesis. However, it is not clear from the current evidences whether 3D
      printed construct plays a role in guiding tissue self-organization in vitro.
      Based on our previous study, we bioprinted a 3D matrix as the restrictive niche
      for direct sweat gland differentiation of epidermal progenitors by different pore
      structure (300-MUm or 400-MUm nozzle diameters printed) and reported a long-term
      gradual transition of differentiated cells into glandular morphogenesis occurs
      within the 3D construct in vitro. At the initial 14-day culture, an accelerated
      cell differentiation was achieved with inductive cues released along with gelatin
      reduction. After protein release completed, the 3D construct guide the self
      organized formation of sweat gland tissues, which is similar to that of the
      natural developmental process. However, glandular morphogenesis was only observed
      in 300-MUm-printed constructs. In the absence of 3D architectural support,
      glandular morphogenesis was not occurred. This striking finding made us to
      identify a previously unknown role of the 3D-printed structure in glandular
      tissue regeneration, and this self-organizing strategy can be applied to forming
      other tissues in vitro.

PMID- 27694986
TI  - Mapping light-driven conformational changes within the photosensory module of
      plant phytochrome B.
AB  - Organisms developed different photoreceptors to be able to adapt to changing
      environmental light conditions. Phytochromes are red/far-red (r/fr) photochromic
      photoreceptors that belong to the classical photoreceptors along with
      cryptochromes and phototropins. They convert absorbed light into a biological
      signal by switching between two states in a light-dependent manner therefore
      enabling the light control downstream signalling. Their Pfr conformation is the
      biological active form in plants, but until now only a structure of the ground
      state (Pr) was solved. Here, the authors provide information about structural
      changes occurring during photoconversion within phytochrome B and identify
      possible interaction sites for its N-terminal extension (NTE) utilising
      hydrogen/deuterium exchange rate analyses of its amide backbone. Especially, the
      newly identified light-dependency of two regions in the NTE are of particular
      interest for understanding the involvement of the phytochrome's NTE in the
      regulation of its downstream signalling.

PMID- 27694989
TI  - Biomimetic Nanofibrillation in Two-Component Biopolymer Blends with Structural
      Analogs to Spider Silk.
AB  - Despite the enormous potential in bioinspired fabrication of high-strength
      structure by mimicking the spinning process of spider silk, currently accessible
      routes (e.g., microfluidic and electrospinning approaches) still have substantial
      function gaps in providing precision control over the nanofibrillar
      superstructure, crystalline morphology or molecular orientation. Here the concept
      of biomimetic nanofibrillation, by copying the spiders' spinning principles, was
      conceived to build silk-mimicking hierarchies in two-phase biodegradable blends,
      strategically involving the stepwise integration of elongational shear and high
      pressure shear. Phase separation confined on nanoscale, together with deformation
      of discrete phases and pre-alignment of polymer chains, was triggered in the
      elongational shear, conferring the readiness for direct nanofibrillation in the
      latter shearing stage. The orderly aligned nanofibrils, featuring an ultralow
      diameter of around 100 nm and the "rigid-soft" system crosslinked by nanocrystal
      domains like silk protein dopes, were secreted by fine nanochannels. The
      incorporation of multiscale silk-mimicking structures afforded exceptional
      combination of strength, ductility and toughness for the nanofibrillar polymer
      composites. The proposed spider spinning-mimicking strategy, offering the
      biomimetic function integration unattainable with current approaches, may prompt
      materials scientists to pursue biopolymer mimics of silk with high performance
      yet light weight.

PMID- 27694988
TI  - Monosodium urate crystal-induced pro-interleukin-1beta production is post
      transcriptionally regulated via the p38 signaling pathway in human monocytes.
AB  - IL-1beta is a key mediator of sterile inflammation in response to endogenous
      particulates, a type of damage-associated molecular pattern (DAMPs) molecule
      derived from damaged cells. Despite the well-known role of sterile particulates
      such as monosodium urate (MSU) crystals as inflammasome inducers in
      monocytes/macrophages, little is known regarding how pro-IL-1beta synthesis is
      induced under sterile inflammatory conditions. We provide evidence that MSU
      crystals post-transcriptionally induce the rapid production of pro-IL-1beta in
      human primary monocytes. Metabolic labeling and pull-down assays for newly
      synthesized proteins clearly showed that MSU crystals rapidly, within 30 min,
      induce the synthesis of pro-IL-1beta as well as global proteins. Notably, MSU
      crystal-induced pro-IL-1beta synthesis is selectively dependent on the p38 MAPK
      pathway, whereas global protein synthesis is mediated via the mTOR, ERK1/2, and
      p38 pathways. Furthermore, inhibition of Mnk1, a substrate of p38, blocked MSU
      crystal-induced pro-IL-1beta synthesis downstream of eIF4E phosphorylation. In
      addition, the p38 MAPK pathway leading to phosphorylation of MK2 was also
      critical for stabilization of pro-IL-1beta mRNA following MSU stimulation. Our
      findings demonstrate that post-transcriptional regulation via p38 MAPK plays a
      central role in the rapid synthesis of pro-IL-1beta in response to MSU crystals,
      which is an essential step for IL-1beta production in human monocytes.

PMID- 27694990
TI  - History-dependent variability in population dynamics during evidence accumulation
      in cortex.
AB  - We studied how the posterior parietal cortex combines new information with
      ongoing activity dynamics as mice accumulate evidence during a virtual navigation
      task. Using new methods to analyze population activity on single trials, we found
      that activity transitioned rapidly between different sets of active neurons. Each
      event in a trial, whether an evidence cue or a behavioral choice, caused seconds
      long modifications to the probabilities that govern how one activity pattern
      transitions to the next, forming a short-term memory. A sequence of evidence cues
      triggered a chain of these modifications resulting in a signal for accumulated
      evidence. Multiple distinguishable activity patterns were possible for the same
      accumulated evidence because representations of ongoing events were influenced by
      previous within- and across-trial events. Therefore, evidence accumulation need
      not require the explicit competition between groups of neurons, as in winner-take
      all models, but could instead emerge implicitly from general dynamical properties
      that instantiate short-term memory.

PMID- 27694992
TI  - Computational principles of synaptic memory consolidation.
AB  - Memories are stored and retained through complex, coupled processes operating on
      multiple timescales. To understand the computational principles behind these
      intricate networks of interactions, we construct a broad class of synaptic models
      that efficiently harness biological complexity to preserve numerous memories by
      protecting them against the adverse effects of overwriting. The memory capacity
      scales almost linearly with the number of synapses, which is a substantial
      improvement over the square root scaling of previous models. This was achieved by
      combining multiple dynamical processes that initially store memories in fast
      variables and then progressively transfer them to slower variables. Notably, the
      interactions between fast and slow variables are bidirectional. The proposed
      models are robust to parameter perturbations and can explain several properties
      of biological memory, including delayed expression of synaptic modifications,
      metaplasticity, and spacing effects.

PMID- 27694993
TI  - Ultra-rare disruptive and damaging mutations influence educational attainment in
      the general population.
AB  - Disruptive, damaging ultra-rare variants in highly constrained genes are enriched
      in individuals with neurodevelopmental disorders. In the general population, this
      class of variants was associated with a decrease in years of education (YOE).
      This effect was stronger among highly brain-expressed genes and explained more
      YOE variance than pathogenic copy number variation but less than common variants.
      Disruptive, damaging ultra-rare variants in highly constrained genes influence
      the determinants of YOE in the general population.

PMID- 27694996
TI  - The origin of hyperferroelectricity in LiBO3 (B = V, Nb, Ta, Os).
AB  - The electronic and structural properties of LiBO3 (B = V, Nb, Ta, Os) are
      investigated via first-principles methods. We show that LiBO3 belong to the
      recently proposed hyperferroelectrics (hyperFEs), i.e., they all have unstable
      longitudinal optic phonon modes. Especially, the ferroelectric-like instability
      in the metal LiOsO3, whose optical dielectric constant goes to infinity, is a
      limiting case of hyperFEs. Via an effective Hamiltonian, we further show that, in
      contrast to normal proper ferroelectricity, in which the ferroelectric
      instability usually comes from long-range coulomb interactions, the hyperFE
      instability is due to the structure instability driven by short-range
      interactions. This could happen in systems with large ion size mismatches, which
      therefore provides a useful guidance in searching for novel hyperFEs.

PMID- 27694994
TI  - Increased burden of ultra-rare protein-altering variants among 4,877 individuals
      with schizophrenia.
AB  - By analyzing the exomes of 12,332 unrelated Swedish individuals, including 4,877
      individuals affected with schizophrenia, in ways informed by exome sequences from
      45,376 other individuals, we identified 244,246 coding-sequence and splice-site
      ultra-rare variants (URVs) that were unique to individual Swedes. We found that
      gene-disruptive and putatively protein-damaging URVs (but not synonymous URVs)
      were more abundant among individuals with schizophrenia than among controls (P =
      1.3 * 10-10). This elevation of protein-compromising URVs was several times
      larger than an analogously elevated rate for de novo mutations, suggesting that
      most rare-variant effects on schizophrenia risk are inherited. Among individuals
      with schizophrenia, the elevated frequency of protein-compromising URVs was
      concentrated in brain-expressed genes, particularly in neuronally expressed
      genes; most of this elevation arose from large sets of genes whose RNAs have been
      found to interact with synaptically localized proteins. Our results suggest that
      synaptic dysfunction may mediate a large fraction of strong, individually rare
      genetic influences on schizophrenia risk.

PMID- 27694995
TI  - Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle
      and Wnt signaling.
AB  - De novo mutations in CHD8 are strongly associated with autism spectrum disorder,
      but the basic biology of CHD8 remains poorly understood. Here we report that Chd8
      knockdown during cortical development results in defective neural progenitor
      proliferation and differentiation that ultimately manifests in abnormal neuronal
      morphology and behaviors in adult mice. Transcriptome analysis revealed that
      while Chd8 stimulates the transcription of cell cycle genes, it also precludes
      the induction of neural-specific genes by regulating the expression of PRC2
      complex components. Furthermore, knockdown of Chd8 disrupts the expression of key
      transducers of Wnt signaling, and enhancing Wnt signaling rescues the
      transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that
      these roles of Chd8 and the dynamics of Chd8 expression during development help
      negotiate the fine balance between neural progenitor proliferation and
      differentiation. Together, these observations provide new insights into the
      neurodevelopmental role of Chd8.

PMID- 27694999
TI  - The impact of non-severe burn injury on cardiac function and long-term
      cardiovascular pathology.
AB  - Severe burn injury significantly affects cardiovascular function for up to 3
      years. However, whether this leads to long-term pathology is unknown. The impact
      of non-severe burn injury, which accounts for over 80% of admissions in developed
      countries, has not been investigated. Using a rodent model of non-severe burn
      injury with subsequent echocardiography we showed significantly increased left
      ventricular end systolic diameter (LVESD) and ventricular wall thickness at up to
      3 months post-injury. Use of propranolol abrogated the changes in cardiac
      measures observed. Subsequently we investigated changes in a patient cohort with
      non-severe injury. Echocardiography measured at baseline and at 3 months post
      injury showed increased LVESD at 3 months and significantly decreased posterior
      wall diameter. Finally, 32 years of Western Australian hospital records were used
      to investigate the incidence of cardiovascular disease admissions after burn
      injury. People who had experienced a burn had increased hospital admissions and
      length of stay for cardiovascular diseases when compared to a matched uninjured
      cohort. This study presents animal, patient and population data that strongly
      suggest non-severe burn injury has significant effects on cardiovascular function
      and long-term morbidity in some burn patients. Identification of patients at risk
      will promote better intervention and outcomes for burn patients.

PMID- 27694997
TI  - A capillary electrophoresis coupled to mass spectrometry pipeline for long term
      comparable assessment of the urinary metabolome.
AB  - Although capillary electrophoresis coupled to mass spectrometry (CE-MS) has
      potential application in the field of metabolite profiling, very few studies
      actually used CE-MS to identify clinically useful body fluid metabolites. Here we
      present an optimized CE-MS setup and analysis pipeline to reproducibly explore
      the metabolite content of urine. We show that the use of a beveled tip capillary
      improves the sensitivity of detection over a flat tip. We also present a novel
      normalization procedure based on the use of endogenous stable urinary metabolites
      identified in the combined metabolome of 75 different urine samples from healthy
      and diseased individuals. This method allows a highly reproducible comparison of
      the same sample analyzed nearly 130 times over a range of 4 years. To demonstrate
      the use of this pipeline in clinical research we compared the urinary metabolome
      of 34 newborns with ureteropelvic junction (UPJ) obstruction and 15 healthy
      newborns. We identified 32 features with differential urinary abundance.
      Combination of the 32 compounds in a SVM classifier predicted with 76%
      sensitivity and 86% specificity UPJ obstruction in a separate validation cohort
      of 24 individuals. Thus, this study demonstrates the feasibility to use CE-MS as
      a tool for the identification of clinically relevant urinary metabolites.

PMID- 27694998
TI  - Glatiramer acetate treatment normalized the monocyte activation profile in MS
      patients to that of healthy controls.
AB  - Multiple sclerosis (MS) is an immune-mediated disease of the central nervous
      system, and monocytes contribute to MS-associated neuroinflammation. While
      classically activated monocytes promote inflammation, type II-activated monocytes
      improve the course of MS. This study investigated type II activation of monocytes
      and their two main subsets, namely CD14+ (CD14++CD16- subset) and CD16+ monocytes
      (CD14+CD16+ subset), by glatiramer acetate (GA) or intravenous immunoglobulin
      associated immune complexes (IC), both of which are known MS treatments. Total
      monocytes and subsets were isolated from peripheral blood mononuclear cells
      (PBMC) of healthy controls, untreated MS patients (MS) and GA-treated MS patients
      (GA-MS). In contrast to the more activated ex vivo profile of monocytes from the
      MS group, monocytes from the GA-MS group resembled those from healthy controls.
      In vitro type II activation with GA primarily reduced CD40, CD86 and IL-12p40
      whereas type II activation with IC consistently reduced CD40 but increased
      interleukin-10 (IL-10), suggesting that the GA and IC activation pathways are
      distinct. Moreover, while GA treatment reduced IL-12p40 by both CD14+ and CD16+
      subsets, IC treatment only enhanced IL-10 by the CD16+ subset. Further analysis
      of the CD16+ subset revealed that MS patients had a greatly expanded CD14+CD16int
      population while both CD14+CD16int and CD14lowCD16high monocyte populations were
      expanded in GA-MS patients. Finally, a global analysis of the ex vivo monocyte
      data indicated that GA treatment distinctly altered the monocyte profile of MS
      patients, further supporting the idea that GA directly targets monocytes.

PMID- 27695000
TI  - Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid
      progenitors.
AB  - The final stages of restriction to the T cell lineage occur in the thymus after
      the entry of thymus-seeding progenitors (TSPs). The identity and lineage
      potential of TSPs remains unclear. Because the first embryonic TSPs enter a non
      vascularized thymic rudiment, we were able to directly image and establish the
      functional and molecular properties of embryonic thymopoiesis-initiating
      progenitors (T-IPs) before their entry into the thymus and activation of Notch
      signaling. T-IPs did not include multipotent stem cells or molecular evidence of
      T cell-restricted progenitors. Instead, single-cell molecular and functional
      analysis demonstrated that most fetal T-IPs expressed genes of and had the
      potential to develop into lymphoid as well as myeloid components of the immune
      system. Moreover, studies of embryos deficient in the transcriptional regulator
      RBPJ demonstrated that canonical Notch signaling was not involved in pre-thymic
      restriction to the T cell lineage or the migration of T-IPs.

PMID- 27695001
TI  - Identification of a role for TRIM29 in the control of innate immunity in the
      respiratory tract.
AB  - The respiratory tract is heavily populated with innate immune cells, but the
      mechanisms that control such cells are poorly defined. Here we found that the E3
      ubiquitin ligase TRIM29 was a selective regulator of the activation of alveolar
      macrophages, the expression of type I interferons and the production of
      proinflammatory cytokines in the lungs. We found that deletion of TRIM29 enhanced
      macrophage production of type I interferons and protected mice from infection
      with influenza virus, while challenge of Trim29-/- mice with Haemophilus
      influenzae resulted in lethal lung inflammation due to massive production of
      proinflammatory cytokines by macrophages. Mechanistically, we demonstrated that
      TRIM29 inhibited interferon-regulatory factors and signaling via the
      transcription factor NF-kappaB by degrading the adaptor NEMO and that TRIM29
      directly bound NEMO and subsequently induced its ubiquitination and proteolytic
      degradation. These data identify TRIM29 as a key negative regulator of alveolar
      macrophages and might have important clinical implications for local immunity and
      immunopathology.

PMID- 27695002
TI  - Suppression by TFR cells leads to durable and selective inhibition of B cell
      effector function.
AB  - Follicular regulatory T cells (TFR cells) inhibit follicular helper T cell (TFH
      cell)-mediated antibody production. The mechanisms by which TFR cells exert their
      key immunoregulatory functions are largely unknown. Here we found that TFR cells
      induced a distinct suppressive state in TFH cells and B cells, in which effector
      transcriptional signatures were maintained but key effector molecules and
      metabolic pathways were suppressed. The suppression of B cell antibody production
      and metabolism by TFR cells was durable and persisted even in the absence of TFR
      cells. This durable suppression was due in part to epigenetic changes. The
      cytokine IL-21 was able to overcome TFR cell-mediated suppression and inhibited
      TFR cells and stimulated B cells. By determining mechanisms of TFR cell-mediated
      suppression, we have identified methods for modulating the function of TFR cells
      and antibody production.

PMID- 27695004
TI  - Time-resolved metabolomics analysis of individual differences during the early
      stage of lipopolysaccharide-treated rats.
AB  - Lipopolysaccharide (LPS) can lead to uncontrollable cytokine production and
      eventually cause fatal sepsis syndrome. Individual toxicity difference of LPS has
      been widely reported. In our study we observed that two thirds of the rats
      (24/36) died at a given dose of LPS, while the rest (12/36) survived. Tracking
      the dynamic metabolic change in survival and non-survival rats in the early stage
      may reveal new system information to understand the inter-individual variation in
      response to LPS. As the time-resolved datasets are very complex and no single
      method can elucidate the problem clearly and comprehensively, the static and
      dynamic metabolomics methods were employed in combination as cross-validation.
      Intriguingly, some common results have been observed. Lipids were the main
      different metabolites between survival and non-survival rats in pre-dose serum
      and in the early stage of infection with LPS. The LPS treatment led to S-adenosly
      methionine and total cysteine individual difference in early stage, and
      subsequent significant perturbations in energy metabolism and oxidative stress.
      Furthermore, cytokine profiles were analyzed to identify potential biological
      associations between cytokines and specific metabolites. Our collective findings
      may provide some heuristic guidance for elucidating the underlying mechanism of
      individual difference in LPS-mediated disease.

PMID- 27695003
TI  - Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for
      suppression.
AB  - CD4+ effector T cells (Teff cells) and regulatory T cells (Treg cells) undergo
      metabolic reprogramming to support proliferation and immunological function.
      Although signaling via the lipid kinase PI(3)K (phosphatidylinositol-3-OH
      kinase), the serine-threonine kinase Akt and the metabolic checkpoint kinase
      complex mTORC1 induces both expression of the glucose transporter Glut1 and
      aerobic glycolysis for Teff cell proliferation and inflammatory function, the
      mechanisms that regulate Treg cell metabolism and function remain unclear. We
      found that Toll-like receptor (TLR) signals that promote Treg cell proliferation
      increased PI(3)K-Akt-mTORC1 signaling, glycolysis and expression of Glut1.
      However, TLR-induced mTORC1 signaling also impaired Treg cell suppressive
      capacity. Conversely, the transcription factor Foxp3 opposed PI(3)K-Akt-mTORC1
      signaling to diminish glycolysis and anabolic metabolism while increasing
      oxidative and catabolic metabolism. Notably, Glut1 expression was sufficient to
      increase the number of Treg cells, but it reduced their suppressive capacity and
      Foxp3 expression. Thus, inflammatory signals and Foxp3 balance mTORC1 signaling
      and glucose metabolism to control the proliferation and suppressive function of
      Treg cells.

PMID- 27695005
TI  - Adsorptive Removal of Pharmaceuticals and Personal Care Products from Water with
      Functionalized Metal-organic Frameworks: Remarkable Adsorbents with Hydrogen
      bonding Abilities.
AB  - Adsorption of typical pharmaceuticals and personal care products (PPCPs) (such as
      naproxen, ibuprofen and oxybenzone) from aqueous solutions was studied by using
      the highly porous metal-organic framework (MOF) MIL-101 with and without
      functionalization. Adsorption results showed that MIL-101s with H-donor
      functional groups such as -OH and -NH2 were very effective for naproxen
      adsorption, despite a decrease in porosity, probably because of H-bonding between
      O atoms on naproxen and H atoms on the adsorbent. For this reason, MIL-101 with
      two functional groups capable of H-bonding (MIL-101-(OH)2) exhibited remarkable
      adsorption capacity based on adsorbent surface area. The favorable contributions
      of -OH and -(OH)2 on MIL-101 in the increased adsorption of ibuprofen and
      oxybenzone (especially based on porosity) confirmed again the importance of H
      bonding mechanism. The adsorbent with the highest adsorption capacity, MIL-101
      OH, was very competitive when compared with carbonaceous materials, mesoporous
      materials, and pristine MIL-101. Moreover, the MIL-101-OH could be recycled
      several times by simply washing with ethanol, suggesting potential application in
      the adsorptive removal of PPCPs from water.

PMID- 27695007
TI  - Apelin - a potential target in the diagnosis and treatment of the diseases of
      civilization.

PMID- 27695006
TI  - Discovery of Isoquinolinoquinazolinones as a Novel Class of Potent PPARgamma
      Antagonists with Anti-adipogenic Effects.
AB  - Conformational change in helix 12 can alter ligand-induced PPARgamma activity;
      based on this reason, isoquinolinoquinazolinones, structural homologs of
      berberine, were designed and synthesized as PPARgamma antagonists. Computational
      docking and mutational study indicated that isoquinolinoquinazolinones form
      hydrogen bonds with the Cys285 and Arg288 residues of PPARgamma. Furthermore, SPR
      results demonstrated strong binding affinity of isoquinolinoquinazolinones
      towards PPARgamma. Additionally, biological assays showed that this new series of
      PPARgamma antagonists more strongly inhibit adipocyte differentiation and
      PPARgamma2-induced transcriptional activity than GW9662.

PMID- 27695008
TI  - The effect of Basic Life Support (BLS) education on secondary school students'
      willingness to and reasons not to perform BLS in real life.

PMID- 27695009
TI  - Cost analysis of minimally invasive compared to conventional mitral valve
      surgery.

PMID- 27695010
TI  - Heart-type fatty acid-binding protein as a diagnostic biochemical marker for
      early detection of myocardial infarction.

PMID- 27695011
TI  - Physiological and symptom effects of changing posture from sitting to supine, and
      vice versa, in stable chronic heart failure.

PMID- 27695012
TI  - Managing periprocedural anticoagulation therapy in patients undergoing device
      implantation: survey in Germany, Austria and Switzerland.

PMID- 27695013
TI  - Subclinical left ventricular deterioration in patients with erectile dysfunction.

PMID- 27694991
TI  - Novel genetic loci underlying human intracranial volume identified through genome
      wide association.
AB  - Intracranial volume reflects the maximally attained brain size during
      development, and remains stable with loss of tissue in late life. It is highly
      heritable, but the underlying genes remain largely undetermined. In a genome-wide
      association study of 32,438 adults, we discovered five previously unknown loci
      for intracranial volume and confirmed two known signals. Four of the loci were
      also associated with adult human stature, but these remained associated with
      intracranial volume after adjusting for height. We found a high genetic
      correlation with child head circumference (rhogenetic = 0.748), which indicates a
      similar genetic background and allowed us to identify four additional loci
      through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were
      also related to childhood and adult cognitive function, and Parkinson's disease,
      and were enriched near genes involved in growth pathways, including PI3K-AKT
      signaling. These findings identify the biological underpinnings of intracranial
      volume and their link to physiological and pathological traits.

PMID- 27695014
TI  - Rosuvastatin and vascular oxidative stress induced by diesel exhaust particles.

PMID- 27695015
TI  - Meta-analysis of two different surgical treatments of ischaemic mitral
      regurgitation with the same outcome: mitral valve repair vs mitral valve
      replacement.

PMID- 27695016
TI  - Haemoglobin A1c as a marker predicting extent and severity of coronary artery
      disease in non-diabetic patients.

PMID- 27695017
TI  - Prognostic utility of biomarker growth differentiation factor- 15 in patients
      with acute decompensated heart failure.

PMID- 27695018
TI  - Remote ischaemic preconditioning reduces myocardial ischaemic reperfusion injury
      in patients with ST-elevation myocardial infarction undergoing primary
      percutaneous coronary intervention.

PMID- 27695019
TI  - Clinical characteristics and in-hospital mortality of very elderly patients
      hospitalized for acute decompensated heart failure: experience at a single
      cardiovascular centre in Japan.

PMID- 27695020
TI  - Predictors of successful atrial and ventricular auto capture pacemaker algorithm
      post implantation: single-centre experience.

PMID- 27695021
TI  - Left ventricular aneurysm: true, false or both?

PMID- 27695023
TI  - The diabolo approach to descending aorta dissections.

PMID- 27695022
TI  - Myocardial metastasis mimicking acute coronary syndrome.

PMID- 27695024
TI  - Lymphoma with massive cardiac involvement.

PMID- 27695025
TI  - Unusual sequel of dual-chamber ICD implantation.

PMID- 27695026
TI  - 'Toothpaste tumour' or severe caseous calcification of the mitral valve annulus:
      think twice before you brush!

PMID- 27695027
TI  - Torsades de pointes complicating complete heart block with QT interval
      prolongation.

PMID- 27695028
TI  - Non-compaction can be congenital, muscular, or compensatory.

PMID- 27695030
TI  - Phosphorylation of Staphylococcus aureus Protein-Tyrosine Kinase Affects the
      Function of Glucokinase and Biofilm Formation.
AB  - BACKGROUND: When Staphylococcus aureus is grown in the presence of high
      concentration of external glucose, this sugar is phosphorylated by glucokinase
      (glkA) to form glucose-6-phosphate. This product subsequently enters into
      anabolic phase, which favors biofilm formation. The presence of ROK (repressor
      protein, open reading frame, sugar kinase) motif, phosphate-1 and -2 sites, and
      tyrosine kinase sites in glkA of S. aureus indicates that phosphorylation must
      regulate the glkA activity. The aim of the present study was to identify the
      effect of phosphorylation on the function of S. aureus glkA and biofilm
      formation. METHODS: Pure glkA and protein-tyrosine kinase (BYK) of S. aureus ATCC
      12600 were obtained by fractionating the cytosolic fractions of glkA1 and BYK-1
      expressing recombinant clones through nickel metal chelate column. The pure glkA
      was used as a substrate for BYK and the phosphorylation of glkA was confirmed by
      treating with reagent A and resolving in SDS-PAGE, as well as staining with
      reagent A. The kinetic parameters of glkA and phosphorylated glkA were determined
      spectrophotometrically, and in silico tools were used for validation. S. aureus
      was grown in brain heart infusion broth, which was supplemented with glucose, and
      then biofilm units were calculated. RESULTS: Fourfold elevated glkA activity was
      observed upon the phosphorylation by BYK. Protein-protein docking analysis
      revealed that glkA structure docked close to the adenosine triphosphate-binding
      site of BYK structure corroborating the kinetic results. Further, S. aureus grown
      in the presence of elevated glucose concentration exhibited an increase in the
      rate of biofilm formation. CONCLUSION: The elevated function of glkA is an
      essential requirement for increased biofilm units in S. aureus, a key pathogenic
      factor that helps its survival and spread the infection.

PMID- 27695033
TI  - An Empirical Biomarker-Based Calculator for Cystic Index in a Model of Autosomal
      Recessive Polycystic Kidney Disease-The Nieto-Narayan Formula.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is associated with
      progressive enlargement of the kidneys fuelled by the formation and expansion of
      fluid-filled cysts. The disease is congenital and children that do not succumb to
      it during the neonatal period will, by age 10 years, more often than not, require
      nephrectomy+renal replacement therapy for management of both pain and renal
      insufficiency. Since increasing cystic index (CI; percent of kidney occupied by
      cysts) drives both renal expansion and organ dysfunction, management of these
      patients, including decisions such as elective nephrectomy and prioritization on
      the transplant waitlist, could clearly benefit from serial determination of CI.
      So also, clinical trials in ARPKD evaluating the efficacy of novel drug
      candidates could benefit from serial determination of CI. Although ultrasound is
      currently the imaging modality of choice for diagnosis of ARPKD, its utilization
      for assessing disease progression is highly limited. Magnetic resonance imaging
      or computed tomography, although more reliable for determination of CI, are
      expensive, time-consuming and somewhat impractical in the pediatric population.
      Using a well-established mammalian model of ARPKD, we undertook a big data-like
      analysis of minimally- or non-invasive blood and urine biomarkers of renal
      injury/dysfunction to derive a family of equations for estimating CI. We then
      applied a signal averaging protocol to distill these equations to a single
      empirical formula for calculation of CI. Such a formula will eventually find use
      in identifying and monitoring patients at high risk for progressing to end-stage
      renal disease and aid in the conduct of clinical trials.

PMID- 27695032
TI  - Genomic and Evolutionary Analysis of Two Salmonella enterica Serovar Kentucky
      Sequence Types Isolated from Bovine and Poultry Sources in North America.
AB  - Salmonella enterica subsp. enterica serovar Kentucky is frequently isolated from
      healthy poultry and dairy cows and is occasionally isolated from people with
      clinical disease. A genomic analysis of 119 isolates collected in the United
      States from dairy cows, ground beef, poultry and poultry products, and human
      clinical cases was conducted. Results of the analysis demonstrated that the
      majority of poultry and bovine-associated S. Kentucky were sequence type (ST)
      152. Several bovine-associated (n = 3) and food product isolates (n = 3)
      collected from the United States and the majority of human clinical isolates were
      ST198, a sequence type that is frequently isolated from poultry and occasionally
      from human clinical cases in Northern Africa, Europe and Southeast Asia. A
      phylogenetic analysis indicated that both STs are more closely related to other
      Salmonella serovars than they are to each other. Additionally, there was strong
      evidence of an evolutionary divergence between the poultry-associated and bovine
      associated ST152 isolates that was due to polymorphisms in four core genome
      genes. The ST198 isolates recovered from dairy farms in the United States were
      phylogenetically distinct from those collected from human clinical cases with 66
      core genome SNPs differentiating the two groups, but more isolates are needed to
      determine the significance of this distinction. Identification of S. Kentucky
      ST198 from dairy animals in the United States suggests that the presence of this
      pathogen should be monitored in food-producing animals.

PMID- 27695031
TI  - Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing
      Fungal Drug Resistance and Morphogenesis.
AB  - Fungal pathogens have evolved diverse strategies to sense host-relevant cues and
      coordinate cellular responses, which enable virulence and drug resistance.
      Defining circuitry controlling these traits opens new opportunities for chemical
      diversity in therapeutics, as the cognate inhibitors are rarely explored by
      conventional screening approaches. This has great potential to address the
      pressing need for new therapeutic strategies for invasive fungal infections,
      which have a staggering impact on human health. To explore this approach, we
      focused on a leading human fungal pathogen, Candida albicans, and screened 1,280
      pharmacologically active compounds to identify those that potentiate the activity
      of echinocandins, which are front-line therapeutics that target fungal cell wall
      synthesis. We identified 19 compounds that enhance activity of the echinocandin
      caspofungin against an echinocandin-resistant clinical isolate, with the broad
      spectrum chelator DTPA demonstrating the greatest synergistic activity. We found
      that DTPA increases susceptibility to echinocandins via chelation of magnesium.
      Whole genome sequencing of mutants resistant to the combination of DTPA and
      caspofungin identified mutations in the histidine kinase gene NIK1 that confer
      resistance to the combination. Functional analyses demonstrated that DTPA
      activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations
      block Hog1 activation in response to both caspofungin and DTPA. The combination
      has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse
      model of echinocandin-resistant candidiasis. We found that DTPA not only reduces
      drug resistance but also modulates morphogenesis, a key virulence trait that is
      normally regulated by environmental cues. DTPA induced filamentation via
      depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as
      well as the transcription factors Brg1 and Rob1. Thus, we establish a new
      mechanism by which metal chelation modulates morphogenetic circuitry and
      echinocandin resistance, and illuminate a novel facet to metal homeostasis at the
      host-pathogen interface, with broad therapeutic potential.

PMID- 27695034
TI  - Xenobiotic Metabolism and Gut Microbiomes.
AB  - Humans are exposed to numerous xenobiotics, a majority of which are in the form
      of pharmaceuticals. Apart from human enzymes, recent studies have indicated the
      role of the gut bacterial community (microbiome) in metabolizing xenobiotics.
      However, little is known about the contribution of the plethora of gut microbiome
      in xenobiotic metabolism. The present study reports the results of analyses on
      xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397
      available gut metagenomes from individuals of varying age groups from 8
      nationalities were analyzed. Based on the diversities and abundances of the
      xenobiotic metabolizing enzymes, various bacterial taxa were classified into
      three groups, namely, least versatile, intermediately versatile and highly
      versatile xenobiotic metabolizers. Most interestingly, specific relationships
      were observed between the overall drug consumption profile and the abundance and
      diversity of the xenobiotic metabolizing repertoire in various geographies. The
      obtained differential abundance patterns of xenobiotic metabolizing enzymes and
      bacterial genera harboring them, suggest their links to pharmacokinetic
      variations among individuals. Additional analyses of a few well studied classes
      of drug modifying enzymes (DMEs) also indicate geographic as well as age specific
      trends.

PMID- 27695035
TI  - Diversity Takes Shape: Understanding the Mechanistic and Adaptive Basis of
      Bacterial Morphology.
AB  - The modern age of metagenomics has delivered unprecedented volumes of data
      describing the genetic and metabolic diversity of bacterial communities, but it
      has failed to provide information about coincident cellular morphologies. Much
      like metabolic and biosynthetic capabilities, morphology comprises a critical
      component of bacterial fitness, molded by natural selection into the many
      elaborate shapes observed across the bacterial domain. In this essay, we discuss
      the diversity of bacterial morphology and its implications for understanding both
      the mechanistic and the adaptive basis of morphogenesis. We consider how best to
      leverage genomic data and recent experimental developments in order to advance
      our understanding of bacterial shape and its functional importance.

PMID- 27695036
TI  - Differential Effects of Dietary Fat Content and Protein Source on Bone Phenotype
      and Fatty Acid Oxidation in Female C57Bl/6 Mice.
AB  - BACKGROUND: Glycomacropeptide (GMP) is a 64-amino acid glycophosphopeptide
      released from kappa-casein during cheesemaking that promotes satiety, reduces
      body fat, increases bone mass and infers prebiotic and anti-inflammatory effects.
      The impact of adiposity and gender on bone health is unclear. OBJECTIVE: To
      determine how feeding female mice diets providing 60% Fat Kcal (high-fat) or 13%
      Fat Kcal (control) with either GMP or casein as the protein source impacts: body
      composition, ex vivo fatty acid oxidation, bone (femoral) biomechanical
      performance, and the relationship between body composition and bone. METHODS:
      Weanling female C57Bl/6 mice were fed high-fat (60% Fat Kcal) or control diets
      (13% Fat Kcal) with GMP or casein from 3 to 32 weeks of age with assessment of
      body weight and food intake. Body composition was assessed by dual-energy X-ray
      absorptiometry (DXA). Fatty acid oxidation was measured in liver, muscle, and fat
      tissues using 14C-palmitate. Plasma concentrations of hormones and cytokines were
      determined. Bone biomechanical performance was assessed by the 3-point bending
      test. RESULTS: Female mice fed high-fat diets showed increased fatty acid
      oxidation capacity in both gastrocnemius muscle and brown adipose tissue compared
      to mice fed the control diets with a lower fat content. Despite increased fat
      mass in mice fed the high-fat diets, there was little evidence of glucose
      impairment or inflammation. Mice fed the high-fat diets had significantly greater
      total body bone mineral density (BMD), femoral BMD, and femoral cross-sectional
      area than mice fed the control diets. Femora of mice fed the high-fat diets had
      increased yield load and maximum load before fracture, consistent with greater
      bone strength, but reduced post-yield displacement or ductility, consistent with
      bone brittleness. Female mice fed a high-fat GMP diet displayed increased fat
      oxidation capacity in subcutaneous fat relative to mice fed the high-fat casein
      diet. Regardless of dietary fat content, GMP increased total body bone mineral
      content and femur length. The prebiotic properties of GMP may mediate the
      beneficial effects of GMP on bone. CONCLUSIONS: Female mice adapt to high-fat
      feeding by increasing oxidative capacity in muscle tissue and to a lesser extent
      brown adipose tissue. High-fat feeding in female mice leads to development of a
      bone phenotype where femora show increased BMD and are stronger, yet more
      brittle. The increased brittleness of bone was associated with increased body fat
      content due to high-fat feeding. In summary, high-fat feeding in female mice
      increases mineralization of bone, but negatively impacts bone quality resulting
      in brittle bones.

PMID- 27695038
TI  - Comparison of Confocal and Super-Resolution Reflectance Imaging of Metal Oxide
      Nanoparticles.
AB  - The potential for human exposure to manufactured nanoparticles (NPs) has
      increased in recent years, in part through the incorporation of engineered
      particles into a wide range of commercial goods and medical applications. NP are
      ideal candidates for use as therapeutic and diagnostic tools within biomedicine,
      however concern exists regarding their efficacy and safety. Thus, developing
      techniques for the investigation of NP uptake into cells is critically important.
      Current intracellular NP investigations rely on the use of either Transmission
      Electron Microscopy (TEM), which provides ultrahigh resolution, but involves
      cumbersome sample preparation rendering the technique incompatible with live cell
      imaging, or fluorescent labelling, which suffers from photobleaching, poor
      bioconjugation and, often, alteration of NP surface properties. Reflected light
      imaging provides an alternative non-destructive label free technique well suited,
      but not limited to, the visualisation of NP uptake within model systems, such as
      cells. Confocal reflectance microscopy provides optical sectioning and live
      imaging capabilities, with little sample preparation. However confocal microscopy
      is diffraction limited, thus the X-Y resolution is restricted to ~250 nm,
      substantially larger than the <100 nm size of NPs. Techniques such as super
      resolution light microscopy overcome this fundamental limitation, providing
      increased X-Y resolution. The use of Reflectance SIM (R-SIM) for NP imaging has
      previously only been demonstrated on custom built microscopes, restricting the
      widespread use and limiting NP investigations. This paper demonstrates the use of
      a commercial SIM microscope for the acquisition of super-resolution reflectance
      data with X-Y resolution of 115 nm, a greater than two-fold increase compared to
      that attainable with RCM. This increase in resolution is advantageous for
      visualising small closely spaced structures, such as NP clusters, previously
      unresolvable by RCM. This is advantageous when investigating the subcellular
      trafficking of NP within fluorescently labelled cellular compartments. NP signal
      can be observed using RCM, R-SIM and TEM and a direct comparison is presented.
      Each of these techniques has its own benefits and limitations; RCM and R-SIM
      provide novel complementary information while the combination of modalities
      provides a unique opportunity to gain additional information regarding NP uptake.
      The use of multiple imaging methods therefore greatly enhances the range of NPs
      that can be studied under label-free conditions.

PMID- 27695037
TI  - Comparative Transcriptome Analysis Reveals that a Ubiquitin-Mediated Proteolysis
      Pathway Is Important for Primary and Secondary Hair Follicle Development in
      Cashmere Goats.
AB  - BACKGROUND: The fleece of cashmere goats contains two distinct populations of
      fibers, a short and fine non-medullated insulating cashmere fiber and a long and
      coarse medullated guard hair. The former is produced by secondary follicles (SFs)
      and the later by primary follicles (PFs). Evidence suggests that the induction of
      PFs and SFs may require different signaling pathways. The regulation of BMP2/4
      signaling by noggin and Edar signaling via Downless genes are essential for the
      induction of SFs and PFs, respectively. However, these differently expressed
      genes of the signaling pathway cannot directly distinguish between the PFs and
      SFs. RESULTS: In this study, we selected RNA samples from 11 PFs and 7 SFs that
      included 145,525 exons. The pathway analysis of 4512 differentially expressed
      exons revealed that the most statistically significant metabolic pathway was
      related to the ubiquitin-mediated proteolysis pathway (UMPP) (P<3.32x 10-7). In
      addition, the 51 exons of the UMPP that were differentially expressed between the
      different types of hair follicle (HFs) were compared by cluster analysis. This
      resulted in the PFs and SFs being divided into two classes. The expression level
      of two selected exons was analyzed by qRT-PCR, and the results indicated that the
      expression patterns were consistent with the deep sequencing results obtained by
      RNA-Seq. CONCLUSIONS: Based on the comparative transcriptome analysis of 18 HFs
      from cashmere goats, a large number of differentially expressed exons were
      identified using a high-throughput sequencing approach. This study suggests that
      UMPP activation is a prominent signaling pathway for distinguishing the PFs and
      SFs of cashmere goats. It is also a meaningful contribution to the theoretical
      basis of the biological study of the HFs of cashmere goats and other mammals.

PMID- 27695039
TI  - Transcriptional Regulation of Frizzled-1 in Human Osteoblasts by Sp1.
AB  - The wingless pathway has a powerful influence on bone metabolism and is a
      therapeutic target in skeletal disorders. Wingless signaling is mediated in part
      through the Frizzled (FZD) receptor family. FZD transcriptional regulation is
      poorly understood. Herein we tested the hypothesis that Sp1 plays an important
      role in the transcriptional regulation of FZD1 expression in osteoblasts and
      osteoblast mineralization. To test this hypothesis, we conducted FZD1 promoter
      assays in Saos2 cells with and without Sp1 overexpression. We found that Sp1
      significantly up-regulates FZD1 promoter activity in Saos2 cells. Chromatin
      immunoprecipitation (ChIP) and electrophoretic mobility shift (EMSA) assays
      identified a novel and functional Sp1 binding site at -44 to -40 from the
      translation start site in the FZD1 promoter. The Sp1-dependent activation of the
      FZD1 promoter was abolished by mithramycin A (MMA), an antibiotic affecting both
      Sp1 binding and Sp1 protein levels in Saos2 cells. Similarly, down-regulation of
      Sp1 in hFOB cells resulted in less FZD1 expression and lower alkaline phosphatase
      activity. Moreover, over-expression of Sp1 increased FZD1 expression and Saos2
      cell mineralization while MMA decreased Sp1 and FZD1 expression and Saos2 cell
      mineralization. Knockdown of FZD1 prior to Sp1 overexpression partially abolished
      Sp1 stimulation of osteoblast differentiation markers. Taken together, our
      results suggest that Sp1 plays a role in human osteoblast differentiation and
      mineralization, which is at least partially mediated by Sp1-dependent
      transactivation of FZD1.

PMID- 27695041
TI  - Aspects of Health-Related Factors and Nutritional Care Needs by Survival Stage
      among Female Cancer Patients in South Korea.
AB  - PURPOSE: This study examined diet-related problems and needs associated with
      nutritional care according to survival stage in Korean female cancer survivors.
      METHODS: 186 outpatients (breast or gynecologic cancer survivors) recruited.
      Subjects were classified as (1) extended stage (ES, 2-5 years from diagnosis) and
      (2) long-term stage (LS, >=5 years from diagnosis). Eating habits, changes in
      health related factors, nutritional needs, and quality of life were investigated.
      RESULTS: 43% of ES survivors had diet-related problems (p = .031); ES group
      reported dyspepsia and LS group reported anorexia/nausea as the major problem.
      Half of ES survivors had taste change, decreasing amount of intake, and reduced
      quality of life (p < .05). The LS group had a greater preference for sweet tastes
      than the ES group. According to their diagnosis, ES survivors with breast cancer
      gained weight (27.1%), whereas ES survivors with gynecologic cancer lost their
      body weight (34.5%) significantly. LS breast cancer patients showed great food
      preference for vegetables, whereas those with gynecologic cancer showed an
      increased preference for fish, meat and grain. Approximately 90% of survivors
      demanded nutritional care regarding restricted foods, preventing recurrence,
      particularly in ES survivors (p < .01). Moreover, main factors for nutritional
      care needs were body weight control for breast cancer and food environment for
      gynecologic cancer. CONCLUSION: Survivors have different aspects of diet-related
      problems by survival stage as dyspepsia in ES and anorexia in LS. ES stage had
      changes in dietary patterns and their food consumption have decreased. Most of
      survivors have demanded nutritional care regardless of survival stage. These
      features of each stage should be considered to improve their health.

PMID- 27695040
TI  - The Paradoxical Signals of Two TrkC Receptor Isoforms Supports a Rationale for
      Novel Therapeutic Strategies in ALS.
AB  - Full length TrkC (TrkC-FL) is a receptor tyrosine kinase whose mRNA can be
      spliced to a truncated TrkC.T1 isoform lacking the kinase domain. Neurotrophin-3
      (NT-3) activates TrkC-FL to maintain motor neuron health and function and TrkC.T1
      to produce neurotoxic TNF-alpha; hence resulting in opposing pathways. In mouse
      and human ALS spinal cord, the reduction of miR-128 that destabilizes TrkC.T1
      mRNA results in up-regulated TrkC.T1 and TNF-alpha in astrocytes. We exploited
      conformational differences to develop an agonistic mAb 2B7 that selectively
      activates TrkC-FL, to circumvent TrkC.T1 activation. In mouse ALS, 2B7 activates
      spinal cord TrkC-FL signals, improves spinal cord motor neuron phenotype and
      function, and significantly prolongs life-span. Our results elucidate biological
      paradoxes of receptor isoforms and their role in disease progression, validate
      the concept of selectively targeting conformational epitopes in naturally
      occurring isoforms, and may guide the development of pro-neuroprotective (TrkC
      FL) and anti-neurotoxic (TrkC.T1) therapeutic strategies.

PMID- 27695042
TI  - Subjective Wellbeing, Objective Wellbeing and Inequality in Australia.
AB  - In recent years policy makers and social scientists have devoted considerable
      attention to wellbeing, a concept that refers to people's capacity to live
      healthy, creative and fulfilling lives. Two conceptual approaches dominate
      wellbeing research. The objective approach examines the objective components of a
      good life. The subjective approach examines people's subjective evaluations of
      their lives. In the objective approach how subjective wellbeing relates to
      objective wellbeing is not a relevant research question. The subjective approach
      does investigate how objective wellbeing relates to subjective wellbeing, but has
      focused primarily on one objective wellbeing indicator, income, rather than the
      comprehensive indicator set implied by the objective approach. This paper
      attempts to contribute by examining relationships between a comprehensive set of
      objective wellbeing measures and subjective wellbeing, and by linking wellbeing
      research to inequality research by also investigating how subjective and
      objective wellbeing relate to class, gender, age and ethnicity. We use three
      waves of a representative state-level household panel study from Queensland,
      Australia, undertaken from 2008 to 2010, to investigate how objective measures of
      wellbeing are socially distributed by gender, class, age, and ethnicity. We also
      examine relationships between objective wellbeing and overall life satisfaction,
      providing one of the first longitudinal analyses linking objective wellbeing with
      subjective evaluations. Objective aspects of wellbeing are unequally distributed
      by gender, age, class and ethnicity and are strongly associated with life
      satisfaction. Moreover, associations between gender, ethnicity, class and life
      satisfaction persist after controlling for objective wellbeing, suggesting that
      mechanisms in addition to objective wellbeing link structural dimensions of
      inequality to life satisfaction.

PMID- 27695043
TI  - Hydrodynamics of a Flexible Soft-Rayed Caudal Fin.
AB  - The paper addresses hydrodynamic performance of a slender swimmer furnished with
      a flexible small-aspect-ratio soft-rayed caudal fin. The recoil of the fin is
      found by solving the coupled hydro-elastic problem, in which the structure of the
      fin is modeled by a cantilever of variable cross section and the hydrodynamic
      forces acting on it are modeled using the elongated body theory. It is shown that
      the recoil has practically no effect on the propulsion efficiency of anguilliform
      swimmers, but has a profound effect on the efficiency of carangiform swimmers,
      which can increase almost four-fold between low-speed (low-thrust) cruise and
      high-speed (high-thrust) burst. Whilst the magnitude of this effect furnishes a
      plausible argument in favor of burst-and-coast locomotion strategies, it also
      infers that carangiform swimmers cannot rely on elastic recoil of the caudal fin
      to be efficient throughout the usable speed range, and must actively flex it at
      low speeds.

PMID- 27695044
TI  - Manual Loading Distribution During Carrying Behaviors: Implications for the
      Evolution of the Hominin Hand.
AB  - The human hand is unparalleled amongst primates in its ability to manipulate
      objects forcefully and dexterously. Previous research has predominantly sought to
      explain the evolution of these capabilities through an adaptive relationship
      between more modern human-like anatomical features in the upper limb and
      increased stone tool production and use proficiency. To date, however, we know
      little about the influence that other manipulatively demanding behaviors may have
      had upon the evolution of the human hand. The present study addresses one aspect
      of this deficiency by examining the recruitment of the distal phalanges during a
      range of manual transportation (i.e., carrying) events related to hominin
      behavioral repertoires during the Plio-Pleistocene. Specifically, forces on the
      volar pad of each digit are recorded during the transportation of stones and
      wooden branches that vary in weight and size. Results indicate that in most
      instances, the index and middle fingers are recruited to a significantly greater
      extent than the other three digits during carrying events. Relative force
      differences between digits were, however, dependent upon the size and weight of
      the object transported. Carrying behaviors therefore appear unlikely to have
      contributed to the evolution of the robust thumb anatomy observed in the human
      hand. Rather, results suggest that the manual transportation of objects may
      plausibly have influenced the evolution of the human gripping capabilities and
      the 3rd metacarpal styloid process.

PMID- 27695045
TI  - Tumor Specific Epigenetic Silencing of Corticotropin Releasing Hormone -Binding
      Protein in Renal Cell Carcinoma: Association of Hypermethylation and Metastasis.
AB  - The relevance of Corticotropin Releasing Hormone (CRH)-system in human
      malignancies is a question of growing interest. Here we investigated
      hypermethylation and epigenetic silencing of the CRH-Binding Protein (CRHBP) gene
      in clear cell renal cell cancer (ccRCC). Relative methylation of the CRHBP CpG
      island (CGI) was determined in 17 tumor cell lines as well as 86 ccRCC samples
      and 66 paired normal tissues using pyrosequencing and quantitative methylation
      specific PCR of bisulfite converted DNA. Results were statistically compared with
      relative mRNA expression levels of CRHBP and clinicopathological parameters of
      patients. Re-expression of CRHBP following 5-aza-2'-deoxycytidine treatment was
      investigated by quantitative mRNA expression analysis. Real-time impedance
      analysis was applied for analysis of invasiveness of renal tumor cells following
      si-RNA knockdown of CRHBP expression or ectopic expression of CRHBP. We found the
      CRHBP CGI to be frequently methylated in tumor cell lines of renal, prostatic,
      and bladder cancer. Comparison of methylation in normal and paired renal cancer
      tissue specimens revealed hypermethylation of the CRHBP CGI in tumors (p<1*10
      12). DNA methylation and decreased mRNA expression were correlated (R = 0.83,
      p<1*10-12). Tumor cell lines showed 5-aza-2'-deoxycytidine dependent reduction of
      methylation and re-expression of CRHBP was associated with altered cellular
      invasiveness of renal cancer cells in real-time impedance invasion assays.
      Hypermethylation and inverse relationship with mRNA expression were validated in
      silico using the TCGA network data. We describe for the first time tumor specific
      epigenetic silencing of CRHBP and statistical association with aggressive tumors
      thus suggesting the CRH system to contribute to the development of kidney cancer.

PMID- 27695046
TI  - Role of Dicer1-Dependent Factors in the Paracrine Regulation of Epididymal Gene
      Expression.
AB  - Dicer1 is an endoribonuclease involved in the biogenesis of functional molecules
      such as microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs).
      These small non-coding RNAs are important regulators of post-transcriptional gene
      expression and participate in the control of male fertility. With the knowledge
      that 1) Dicer1-dependent factors are required for proper sperm maturation in the
      epididymis, and that 2) miRNAs are potent mediators of intercellular
      communication in most biological systems, we investigated the role of Dicer1
      dependent factors produced by the proximal epididymis (initial segment/caput)-
      including miRNAs- on the regulation of epididymal gene expression in the distal
      epididymis regions (i.e. corpus and cauda). To this end, we performed comparative
      microarray and ANOVA analyses on control vs. Defb41iCre/wt;Dicer1fl/fl mice in
      which functional Dicer1 is absent from the principal cells of the proximal
      epididymis. We identified 35 and 33 transcripts that displayed significant
      expression level changes in the corpus and cauda regions (Fold change > 2 or < 
      2; p < 0.002), respectively. Among these transcripts, Zn-alpha 2-glycoprotein
      (Azgp1) encodes for a sperm equatorial protein whose expression in the epididymis
      of Dicer1 cKO mice is significantly increased compared to controls. In addition,
      154 miRNAs, including miR-210, miR-672, miR-191 and miR-204, showed significantly
      impaired biogenesis in the absence of Dicer1 from the principal cells of the
      proximal epididymis (Fold change > 2 or < -2; p < 0.01). These miRNAs are
      secreted via extracellular vesicles (EVs) derived from the DC2 epididymal
      principal cell line, and their expression correlates with target transcripts
      involved in distinct biological pathways, as evidenced by in silico analysis.
      Albeit correlative and based on in silico approach, our study proposes that
      Dicer1-dependent factors trigger- directly or not-significant genes expression
      changes in distinct regions of this organ. The paracrine control of functions
      important to post-testicular sperm maturation by Dicer1-dependent factors may
      open new avenues for the identification of molecular targets important to male
      fertility control.

PMID- 27695047
TI  - Contrasting Regulation of NO and ROS in Potato Defense-Associated Metabolism in
      Response to Pathogens of Different Lifestyles.
AB  - Our research provides new insights into how the low and steady-state levels of
      nitric oxide (NO) and reactive oxygen species (ROS) in potato leaves are altered
      after the challenge with the hemibiotroph Phytophthora infestans or the
      necrotroph Botrytis cinerea, with the subsequent rapid and invader-dependent
      modification of defense responses with opposite effects. Mainly in the avirulent
      (avr) P. infestans-potato system, NO well balanced with the superoxide level was
      tuned with a battery of SA-dependent defense genes, leading to the establishment
      of the hypersensitive response (HR) successfully arresting the pathogen.
      Relatively high levels of S-nitrosoglutathione and S-nitrosothiols concentrated
      in the main vein of potato leaves indicated the mobile function of these
      compounds as a reservoir of NO bioactivity. In contrast, low-level production of
      NO and ROS during virulent (vr) P. infestans-potato interactions might be crucial
      in the delayed up-regulation of PR-1 and PR-3 genes and compromised resistance to
      the hemibiotrophic pathogen. In turn, B. cinerea triggered huge NO overproduction
      and governed inhibition of superoxide production by blunting NADPH oxidase.
      Nevertheless, a relatively high level of H2O2 was found owing to the germin-like
      activity in cooperation with NO-mediated HR-like cell death in potato genotypes
      favorable to the necrotrophic pathogen. Moreover, B. cinerea not only provoked
      cell death, but also modulated the host redox milieu by boosting protein
      nitration, which attenuated SA production but not SA-dependent defense gene
      expression. Finally, based on obtained data the organismal cost of having
      machinery for HR in plant resistance to biotrophs is also discussed, while
      emphasizing new efforts to identify other components of the NO/ROS cell death
      pathway and improve plant protection against pathogens of different lifestyles.

PMID- 27695049
TI  - Where Is Current Research on Blockchain Technology?-A Systematic Review.
AB  - Blockchain is a decentralized transaction and data management technology
      developed first for Bitcoin cryptocurrency. The interest in Blockchain technology
      has been increasing since the idea was coined in 2008. The reason for the
      interest in Blockchain is its central attributes that provide security, anonymity
      and data integrity without any third party organization in control of the
      transactions, and therefore it creates interesting research areas, especially
      from the perspective of technical challenges and limitations. In this research,
      we have conducted a systematic mapping study with the goal of collecting all
      relevant research on Blockchain technology. Our objective is to understand the
      current research topics, challenges and future directions regarding Blockchain
      technology from the technical perspective. We have extracted 41 primary papers
      from scientific databases. The results show that focus in over 80% of the papers
      is on Bitcoin system and less than 20% deals with other Blockchain applications
      including e.g. smart contracts and licensing. The majority of research is
      focusing on revealing and improving limitations of Blockchain from privacy and
      security perspectives, but many of the proposed solutions lack concrete
      evaluation on their effectiveness. Many other Blockchain scalability related
      challenges including throughput and latency have been left unstudied. On the
      basis of this study, recommendations on future research directions are provided
      for researchers.

PMID- 27695048
TI  - Vietnam, a Hotspot for Chromosomal Diversity and Cryptic Species in Black Flies
      (Diptera: Simuliidae).
AB  - The increasing attention on Vietnam as a biodiversity hotspot prompted an
      investigation of the potential for cryptic diversity in black flies, a group well
      known elsewhere for its high frequency of isomorphic species. We analyzed the
      banding structure of the larval polytene chromosomes in the Simulium tuberosum
      species group to probe for diversity beyond the morphological level. Among 272
      larvae, 88 different chromosomal rearrangements, primarily paracentric
      inversions, were discovered in addition to 25 already known in the basic
      sequences of the group in Asia. Chromosomal diversity in Vietnam far exceeds that
      known for the group in Thailand, with only about 5% of the rearrangements shared
      between the two countries. Fifteen cytoforms and nine morphoforms were revealed
      among six nominal species in Vietnam. Chromosomal evidence, combined with
      available molecular and morphological evidence, conservatively suggests that at
      least five of the cytoforms are valid species, two of which require formal names.
      The total chromosomal rearrangements and species (15) now known from the group in
      Vietnam far exceed those of any other area of comparable size in the world,
      supporting the country's status as a biodiversity hotspot. Phylogenetic inference
      based on uniquely shared, derived chromosomal rearrangements supports the
      clustering of cytoforms into two primary lineages, the Simulium tani complex and
      the Southeast Asian Simulium tuberosum subgroup. Some of these taxa could be
      threatened by habitat destruction, given their restricted geographical
      distributions and the expanding human population of Vietnam.

PMID- 27695050
TI  - Graphlet Based Metrics for the Comparison of Gene Regulatory Networks.
AB  - Understanding the control of gene expression remains one of the main challenges
      in the post-genomic era. Accordingly, a plethora of methods exists to identify
      variations in gene expression levels. These variations underlay almost all
      relevant biological phenomena, including disease and adaptation to environmental
      conditions. However, computational tools to identify how regulation changes are
      scarce. Regulation of gene expression is usually depicted in the form of a gene
      regulatory network (GRN). Structural changes in a GRN over time and conditions
      represent variations in the regulation of gene expression. Like other biological
      networks, GRNs are composed of basic building blocks called graphlets. As a
      consequence, two new metrics based on graphlets are proposed in this work:
      REConstruction Rate (REC) and REC Graphlet Degree (RGD). REC determines the rate
      of graphlet similarity between different states of a network and RGD identifies
      the subset of nodes with the highest topological variation. In other words, RGD
      discerns how th GRN was rewired. REC and RGD were used to compare the local
      structure of nodes in condition-specific GRNs obtained from gene expression data
      of Escherichia coli, forming biofilms and cultured in suspension. According to
      our results, most of the network local structure remains unaltered in the two
      compared conditions. Nevertheless, changes reported by RGD necessarily imply that
      a different cohort of regulators (i.e. transcription factors (TFs)) appear on the
      scene, shedding light on how the regulation of gene expression occurs when E.
      coli transits from suspension to biofilm. Consequently, we propose that both
      metrics REC and RGD should be adopted as a quantitative approach to conduct
      differential analyses of GRNs. A tool that implements both metrics is available
      as an on-line web server (http://dlab.cl/loto).

PMID- 27695051
TI  - Standardization of A Physiologic Hypoparathyroidism Animal Model.
AB  - Ideal hypoparathyroidism animal models are a prerequisite to developing new
      treatment modalities for this disorder. The purpose of this study was to evaluate
      the feasibility of a model whereby rats were parathyroidectomized (PTX) using a
      fluorescent-identification method and the ideal calcium content of the diet was
      determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and
      PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and
      PTX-HC (n = 10), respectively). Serum parathyroid hormone levels decreased to non
      detectable levels in all PTX groups. All animals in the PTX-FC group died within
      4 days after the operation. All animals survived when supplied calcium in the
      diet. However, serum calcium levels were higher in the PTX-HC than the SHAM
      group. The PTX-NC group demonstrated the most representative modeling of primary
      hypothyroidism. Serum calcium levels decreased and phosphorus levels increased,
      and bone volume was increased. All animals survived without further treatment and
      did not show nephrotoxicity including calcium deposits. These findings
      demonstrate that PTX animal models produced by using the fluorescent
      identification method, and fed a 0.5% calcium diet, are appropriate for
      hypoparathyroidism treatment studies.

PMID- 27695052
TI  - LDL-Cholesterol Increases the Transcytosis of Molecules through Endothelial
      Monolayers.
AB  - Cholesterol has been identified as a causative factor in numerous pathologies
      including atherosclerosis and cancer. One of the frequent effects of elevated
      cholesterol levels in humans is the compromise of endothelial function due to
      activation of pro-inflammatory signalling pathways. While the mechanisms involved
      in endothelial activation by cholesterol during an inflammatory response are well
      established, less is known about the mechanisms by which cholesterol may affect
      endothelial barrier function, which were the subject of the present study. Here
      we show that low density lipoprotein (LDL) increases the permeability of
      endothelial monolayers to high molecular weight dextrans in an LDL receptor and
      cholesterol-dependent manner. The increased permeability seen upon LDL treatment
      was not caused by disruption of cell-to-cell junctions as determined by a normal
      localization of VE-Cadherin and ZO-1 proteins, and no major alterations in
      transendothelial electrical resistance or permeability to fluorescein. We show
      instead that LDL increases the level of high molecular weight transcytosis and
      that this occurs in an LDL receptor, cholesterol and caveolae-dependent way. Our
      findings contribute to our understanding of the systemic pathological effects of
      elevated cholesterol and the transport of cargo through endothelial monolayers.

PMID- 27695053
TI  - Presence of Serum Ferritin before and after Bariatric Surgery: Analysis in
      Dentate and Edentulous Patients.
AB  - Society has changed its own lifestyle, specially its eating habits and physical
      activities, leading to excessive weight and a sedentary behavior, which has
      contributed to obesity increase. Bariatric surgery is the most effective
      treatment to obesity, allowing weight loss and its maintenance. However, it has
      been related high levels of iron deficiency after surgery. A person's nutritional
      status might be affected by total or partial tooth loss. The aim of this
      longitudinal prospective cohort study was to evaluate the levels of serum
      ferritin before and after bariatric surgery and to identify if there is a
      relation with tooth loss. The sample was composed of 50 patients selected and
      assisted at Amaral Carvalho Hospital, located in Jau city, Brazil. The use and
      necessity of prosthesis, dental absence or presence, and serum ferritin dosage
      were evaluated. Student's t test, Univariate analysis, Chi-square and Odds Ratio
      were adopted (p<0.05). There was no significant difference regarding the serum
      ferritin levels between dentate and edentulous patients prior to surgery (p =
      0.436). After surgery, the serum ferritin levels were higher in edentulous
      patients (prosthesis users) when compared to the pre-surgical levels, and the
      post-surgical levels presented significant difference regarding the dentate
      patients (p = 0.024). It can be concluded that rehabilitated patients in
      postoperative period showed better levels of serum ferritin after surgical
      intervention.

PMID- 27695054
TI  - Using YouTube to Disseminate Effective Vaccination Pain Treatment for Babies.
AB  - BACKGROUND: Infant vaccinations are necessary for public health, but are painful,
      causing distress to the infant and caregivers. Breastfeeding and sucrose
      effectively reduce infants' pain during vaccinations, and these strategies are
      recommended in health care provider (HCP)-targeted education and vaccination pain
      guidelines. However studies show these strategies are infrequently used. YouTube
      is a popular medium to publicly share and watch videos, and many consumer posted
      YouTube videos show distressed infants being vaccinated with no pain treatment.
      The aims of this study were to evaluate the reach and impact of a consumer
      targeted YouTube video demonstrating use of effective pain reduction strategies
      during infant vaccinations. METHODS: A brief consumer-targeted video showing two
      infants being vaccinated was posted onto YouTube on October 2013. One infant was
      breastfed and another infant received sucrose by mouth before and during the
      injection. A link to a viewer survey was visible on a banner near the end of the
      video. An intensive strategically planned knowledge dissemination strategy using
      the media, social media and messages to professional organizations took place to
      promote the video. Data analysis of the viewer survey, YouTube analytics of the
      reach of the video in terms of number of views, country of viewers, and comments
      relating to the video took place 12 months after the video was posted. RESULTS:
      Twelve months after posting, the video had 65,478views, 68 comments, 245 likes,
      17 dislikes, and 90 shares. Average duration of viewer time was 65% of the video.
      The viewer survey was completed by 156 (0.24%) viewers; 90 (58%) answered as HCPs
      and 66 (42%) as parents. Survey results showed that the video was persuasive;
      intent to use or support breastfeeding or sucrose was high in both parents and
      HCPs after viewing the video. Comments posted were often emotional in nature, and
      were related to anti-vaccination (n = 26, 38%); effectiveness or positive
      personal experiences (n = 21, 32%); research team comments or promotion (n = 12,
      18%); pro-vaccination (n = 6, 8%) and barriers to using breastfeeding or sucrose
      during vaccinations (n = 3, 4%). CONCLUSION: The video posted onto YouTube
      demonstrating effective pain treatment during infant vaccinations was viewed by
      large numbers of people around the world, however the response rate to the linked
      survey was extremely low. Using YouTube videos for knowledge dissemination has an
      extensive reach, however it is difficult to evaluate impact on behaviours and
      practices.

PMID- 27695055
TI  - An Effective Method to Detect Volatile Intermediates Generated in the
      Bioconversion of Coal to Methane by Gas Chromatography-Mass Spectrometry after In
      Situ Extraction Using Headspace Solid-Phase Micro-Extraction under Strict
      Anaerobic Conditions.
AB  - Bioconversion of coal to methane has gained increased attention in recent decades
      because of its economic and environmental advantages. However, the mechanism of
      this process is difficult to study in depth, partly because of difficulties
      associated with the analysis of intermediates generated in coal bioconversion. In
      this investigation, we report on an effective method to analyze volatile
      intermediates generated in the bioconversion of coal under strict anaerobic
      conditions. We conduct in-situ extraction of intermediates using headspace solid
      phase micro-extraction followed by detection by gas chromatography-mass
      spectrometry. Bioconversion simulation equipment was modified and combined with a
      solid-phase micro-extraction device. In-situ extraction could be achieved by
      using the combined units, to avoid a breakdown in anaerobic conditions and to
      maintain the experiment continuity. More than 30 intermediates were identified
      qualitatively in the conversion process, and the variation in trends of some
      typical intermediates has been discussed. Volatile organic acids (C2-C7) were
      chosen for a quantitative study of the intermediates because of their importance
      during coal bioconversion to methane. Fiber coating, extraction time, and
      solution acidity were optimized in the solid-phase micro-extraction procedure.
      The pressure was enhanced during the bioconversion process to investigate the
      influence of headspace pressure on analyte extraction. The detection limits of
      the method ranged from 0.0006 to 0.02 mmol/L for the volatile organic acids and
      the relative standard deviations were between 4.6% and 11.5%. The volatile
      organic acids (C2-C7) generated in the bioconversion process were 0.01-1.15
      mmol/L with a recovery range from 80% to 105%. The developed method is useful for
      further in-depth research on the bioconversion of coal to methane.

PMID- 27695056
TI  - The Fatty Acid Synthase Inhibitor Platensimycin Improves Insulin Resistance
      without Inducing Liver Steatosis in Mice and Monkeys.
AB  - OBJECTIVES: Platensimycin (PTM) is a natural antibiotic produced by Streptomyces
      platensis that selectively inhibits bacterial and mammalian fatty acid synthase
      (FAS) without affecting synthesis of other lipids. Recently, we reported that
      oral administration of PTM in mouse models (db/db and db/+) with high de novo
      lipogenesis (DNL) tone inhibited DNL and enhanced glucose oxidation, which in
      turn led to net reduction of liver triglycerides (TG), reduced ambient glucose,
      and improved insulin sensitivity. The present study was conducted to explore
      translatability and the therapeutic potential of FAS inhibition for the treatment
      of diabetes in humans. METHODS: We tested PTM in animal models with different DNL
      tones, i.e. intrinsic synthesis rates, which vary among species and are regulated
      by nutritional and disease states, and confirmed glucose-lowering efficacy of PTM
      in lean NHPs with quantitation of liver lipid by MRS imaging. To understand the
      direct effect of PTM on liver metabolism, we performed ex vivo liver perfusion
      study to compare FAS inhibitor and carnitine palmitoyltransferase 1 (CPT1)
      inhibitor. RESULTS: The efficacy of PTM is generally reproduced in preclinical
      models with DNL tones comparable to humans, including lean and established diet
      induced obese (eDIO) mice as well as non-human primates (NHPs). Similar effects
      of PTM on DNL reduction were observed in lean and type 2 diabetic rhesus and lean
      cynomolgus monkeys after acute and chronic treatment of PTM. Mechanistically, PTM
      lowers plasma glucose in part by enhancing hepatic glucose uptake and glycolysis.
      Teglicar, a CPT1 inhibitor, has similar effects on glucose uptake and glycolysis.
      In sharp contrast, Teglicar but not PTM significantly increased hepatic TG
      production, thus caused liver steatosis in eDIO mice. CONCLUSIONS: These findings
      demonstrate unique properties of PTM and provide proof-of-concept of FAS
      inhibition having potential utility for the treatment of diabetes and related
      metabolic disorders.

PMID- 27695057
TI  - The Expression and Prognostic Roles of MCMs in Pancreatic Cancer.
AB  - OBJECTIVES: Minichromosome maintenance (MCM) proteins play important roles in DNA
      replication by interacting with other factors which participate in the regulation
      of DNA synthesis. Abnormal over-expression of MCMs was observed in numerous
      malignancies, such as colorectal cancer. However, the expression of MCMs in
      pancreatic cancer (PC) was less investigated so far. This study was designed to
      analyze the expression and prognostic roles of MCM1-10 in PC based on the data
      provided by The Cancer Genome Atlas (TCGA). METHODS: Pearson chi2 test was
      applied to evaluate the association of MCMs expression with clinicopathologic
      indicators, and biomarkers for tumor biological behaviors. Kaplan-Meier plots and
      log-rank tests were used to assess survival analysis, and univariate and
      multivariate Cox proportional hazard regression models were used to recognize
      independent prognostic factors. RESULTS: MCM1-10 were generally expressed in PC
      samples. The levels of some molecules were markedly correlated with that of
      biomarkers for S phase, proliferation, gemcitabine resistance. And part of these
      molecules over-expression was significantly associated with indicators of disease
      progression, such as depth of tumor invasion and lymph node metastasis.
      Furthermore, MCM2, 4, 6, 8, and 10 over-expression was remarkably associated with
      shorter disease free survival time, and MCM2, 4,8, and 10 over-expression was
      associated with shorter overall survival time. Further multivariate analysis
      suggested that MCM8 was an independent prognostic factor for PC. CONCLUSION: MCMs
      abnormal over-expression was significantly associated with PC progression and
      prognosis. These molecules could be regarded as prognostic and therapeutic
      biomarkers for PC. The roles of MCMs may be vitally important and the underlying
      mechanisms need to be furtherinvestigated.

PMID- 27695058
TI  - Monitoring in Real Time the Formation and Removal of Biofilms from Clinical
      Related Pathogens Using an Impedance-Based Technology.
AB  - Bacteria found in diverse ecosystems grow in a community of aggregated cells that
      favors their survival and colonization. Different extracellular polymeric
      substances are used to entrap this multispecies community forming a biofilm,
      which can be associated to biotic and abiotic surfaces. This widespread and
      successful way of bacterial life, however, can lead to negative effects for human
      activity since many pathogen and spoiling bacteria form biofilms which are not
      easy to eradicate. Therefore, the search for novel anti-biofilm bio-active
      molecules is a very active research area for which simple, reliable, and fast
      screening methods are demanded. In this work we have successfully validated an
      impedance-based method, initially developed for the study of adherent eukaryotic
      cells, to monitor the formation of single-species biofilms of three model
      bacteria in real time. The xCelligence real time cell analyzer (RTCA) equipment
      uses specific microtiter E-plates coated with gold-microelectrodes that detect
      the attachment of adherent cells, thus modifying the impedance signal. In the
      current study, this technology allowed the distinction between biofilm-producers
      and non-producers of Staphylococcus aureus and Staphylococcus epidermidis, as
      well as the formation of Streptococcus mutans biofilms only when sucrose was
      present in the culture medium. Besides, different impedance values permitted
      discrimination among the biofilm-producing strains tested regardless of the
      nature of the polymeric biofilm matrix. Finally, we have continuously monitored
      the inhibition of staphylococcal biofilm formation by the bacteriophage phi-IPLA7
      and the bacteriophage-encoded endolysin LysH5, as well as the removal of a
      preformed biofilm by this last antimicrobial treatment. Results observed with the
      impedance-based method showed high correlation with those obtained with standard
      approaches, such as crystal violet staining and bacteria enumeration, as well as
      with those obtained upon other abiotic surfaces (polystyrene and stainless
      steel). Therefore, this RTCA technology opens new opportunities in the biofilm
      research arena and its application could be further explored for other bacterial
      genera as well as for different bio-active molecules.

PMID- 27695060
TI  - Correction: Identification of microRNAs in Macaca fascicularis (Cynomolgus
      Monkey) by Homology Search and Experimental Validation by Small RNA-Seq and RT
      qPCR Using Kidney Cortex Tissues.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0142708.].

PMID- 27695059
TI  - Genome-Wide Identification of miRNAs and Their Targets Involved in the Developing
      Internodes under Maize Ears by Responding to Hormone Signaling.
AB  - Internode length is one of the decisive factors affecting plant height (PH) and
      ear height (EH), which are closely associated with the lodging resistance,
      biomass and grain yield of maize. miRNAs, currently recognized as important
      transcriptional/ post-transcriptional regulators, play an essential role in plant
      growth and development. However, their roles in developing internodes under maize
      ears remain unclear. To identify the roles of miRNAs and their targets in the
      development of internodes under maize ears, six miRNA and two degradome libraries
      were constructed using the 7th, 8th and 9th internodes of two inbred lines,
      'Xun928' and 'Xun9058', which had significantly different internode lengths. A
      total of 45 and 54 miRNAs showed significant changes for each pairwise comparison
      among the 7th, 8th and 9th internodes of 'Xun9058' and 'Xun928', respectively.
      The expression of 31 miRNAs showed significant changes were common to the
      corresponding comparison groups of the 7th, 8th and 9th internodes of 'Xun9058'
      and 'Xun928'. For the corresponding internodes of 'Xun9058' and 'Xun928',
      compared with the expression of miRNAs in the 7th, 8th and 9th internodes of
      'Xun928', the numbers of up-regulated and down-regulated miRNAs were 11 and 36 in
      the 7th internode, 9 and 45 in the 8th internode, and 9 and 25 in the 9th
      internode of 'Xun9058', respectively. Moreover, 10 miRNA families containing 45
      members showed significant changes at least in two internodes of 'Xun928' by
      comparing with the corresponding internodes of 'Xun9058'. Based on the sequencing
      data, 20 miRNAs related to hormone signaling among the candidates, belonging to
      five conserved miRNA families, were selected for expression profiling using
      quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The five
      miRNA families, zma-miR160, zma-miR167, zma-miR164, zma-miR169 and zma-miR393,
      targeted the genes encoding auxin response factor, N-acetylcysteine domain
      containing protein, nuclear transcription factor Y and auxin signaling F-BOX 2
      through degradome sequencing. The miRNAs might regulate their targets to respond
      to hormone signaling, thereby regulating the internode elongation and development
      under maize ear. These results provide valuable reference for understanding the
      possible regulation mechanism of the ILs under the ear.

PMID- 27695061
TI  - Identification of microRNAs with Dysregulated Expression in Status Epilepticus
      Induced Epileptogenesis.
AB  - The involvement of miRNA in mesial temporal lobe epilepsy (MTLE) pathogenesis has
      increasingly become a focus of epigenetic studies. Despite advances, the number
      of known miRNAs with a consistent expression response during epileptogenesis is
      still small. Addressing this situation requires additional miRNA profiling
      studies coupled to detailed individual expression analyses. Here, we perform a
      miRNA microarray analysis of the hippocampus of Wistar rats 24 hours after intra
      hippocampal pilocarpine-induced Status Epilepticus (H-PILO SE). We identified 73
      miRNAs that undergo significant changes, of which 36 were up-regulated and 37
      were down-regulated. To validate, we selected 5 of these (10a-5p, 128a-3p, 196b
      5p, 352 and 324-3p) for RT-qPCR analysis. Our results confirmed that miR-352 and
      196b-5p levels were significantly higher and miR-128a-3p levels were
      significantly lower in the hippocampus of H-PILO SE rats. We also evaluated
      whether the 3 miRNAs show a dysregulated hippocampal expression at three time
      periods (0h, 24h and chronic phase) after systemic pilocarpine-induced status
      epilepticus (S-PILO SE). We demonstrate that miR-128a-3p transcripts are
      significantly reduced at all time points compared to the naive group. Moreover,
      miR-196b-5p was significantly higher only at 24h post-SE, while miR-352
      transcripts were significantly up-regulated after 24h and in chronic phase
      (epileptic) rats. Finally, when we compared hippocampi of epileptic and non
      epileptic humans, we observed that transcript levels of miRNAs show similar
      trends to the animal models. In summary, we successfully identified two novel
      dysregulated miRNAs (196b-5p and 352) and confirmed miR-128a-3p downregulation in
      SE-induced epileptogenesis. Further functional assays are required to understand
      the role of these miRNAs in MTLE pathogenesis.

PMID- 27695062
TI  - Third-Generation Sequencing and Analysis of Four Complete Pig Liver Esterase Gene
      Sequences in Clones Identified by Screening BAC Library.
AB  - AIM: Pig liver carboxylesterase (PLE) gene sequences in GenBank are incomplete,
      which has led to difficulties in studying the genetic structure and regulation
      mechanisms of gene expression of PLE family genes. The aim of this study was to
      obtain and analysis of complete gene sequences of PLE family by screening from a
      Rongchang pig BAC library and third-generation PacBio gene sequencing. METHODS:
      After a number of existing incomplete PLE isoform gene sequences were analysed,
      primers were designed based on conserved regions in PLE exons, and the whole pig
      genome used as a template for Polymerase chain reaction (PCR) amplification.
      Specific primers were then selected based on the PCR amplification results. A
      three-step PCR screening method was used to identify PLE-positive clones by
      screening a Rongchang pig BAC library and PacBio third-generation sequencing was
      performed. BLAST comparisons and other bioinformatics methods were applied for
      sequence analysis. RESULTS: Five PLE-positive BAC clones, designated BAC-10, BAC
      70, BAC-75, BAC-119 and BAC-206, were identified. Sequence analysis yielded the
      complete sequences of four PLE genes, PLE1, PLE-B9, PLE-C4, and PLE-G2. Complete
      PLE gene sequences were defined as those containing regulatory sequences, exons,
      and introns. It was found that, not only did the PLE exon sequences of the four
      genes show a high degree of homology, but also that the intron sequences were
      highly similar. Additionally, the regulatory region of the genes contained two
      720bps reverse complement sequences that may have an important function in the
      regulation of PLE gene expression. SIGNIFICANCE: This is the first report to
      confirm the complete sequences of four PLE genes. In addition, the study
      demonstrates that each PLE isoform is encoded by a single gene and that the
      various genes exhibit a high degree of sequence homology, suggesting that the PLE
      family evolved from a single ancestral gene. Obtaining the complete sequences of
      these PLE genes provides the necessary foundation for investigation of the
      genetic structure, function, and regulatory mechanisms of the PLE gene family.

PMID- 27695063
TI  - Depression among Parents Two to Six Years Following the Loss of a Child by
      Suicide: A Novel Prediction Model.
AB  - BACKGROUND: Parents who lose a child by suicide have elevated risks of
      depression. No clinical prediction tools exist to identify which suicide-bereaved
      parents will be particularly vulnerable; we aimed to create a prediction model
      for long-term depression for this purpose. METHOD: During 2009 and 2010 we
      collected data using a nationwide study-specific questionnaire among parents in
      Sweden who had lost a child aged 15-30 by suicide in years 2004-2007. Current
      depression was assessed with the Patient Health Questionnaire (PHQ-9) and a
      single question on antidepressant use. We considered 26 potential predictors
      assumed clinically assessable at the time of loss, including socio-economics,
      relationship status, history of psychological stress and morbidity, and suicide
      related circumstances. We developed a novel prediction model using logistic
      regression with all subsets selection and stratified cross-validation. The model
      was assessed for classification performance and calibration, overall and
      stratified by time since loss. RESULTS: In total 666/915 (73%) participated. The
      model showed acceptable classification performance (adjusted area under the curve
      [AUC] = 0.720, 95% confidence interval [CI] 0.673-0.766), but performed
      classification best for those at shortest time since loss. Agreement between
      model-predicted and observed risks was fair, but with a tendency for
      underestimation and overestimation for individuals with shortest and longest time
      since loss, respectively. The identified predictors include female sex (odds
      ratio [OR] = 1.84); sick-leave (OR = 2.81) or unemployment (OR = 1.64);
      psychological premorbidity debuting during the last 10 years, before loss (OR =
      3.64), or more than 10 years ago (OR = 4.96); suicide in biological relatives (OR
      = 1.54); with non-legal guardianship during the child's upbringing (OR = 0.48);
      and non-biological parenthood (OR = 0.22) found as protective. CONCLUSIONS: Our
      prediction model shows promising internal validity, but should be externally
      validated before application. Psychological premorbidity seems to be a prominent
      predictor of long-term depression among suicide-bereaved parents, and thus
      important for healthcare providers to assess.

PMID- 27695065
TI  - Correction: Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine
      (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for
      the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0161845.].

PMID- 27695064
TI  - Studying Closed Hydrodynamic Models of "In Vivo" DNA Perfusion in Pig Liver for
      Gene Therapy Translation to Humans.
AB  - INTRODUCTION: Expressing exogenous genes after naked DNA delivery into
      hepatocytes might achieve sustained and high expression of human proteins. Tail
      vein DNA injection is an efficient procedure for gene transfer in murine liver.
      Hydrodynamic procedures in large animals require organ targeting, and improve
      with liver vascular exclusion. In the present study, two closed liver
      hydrofection models employing the human alpha-1-antitrypsin (hAAT) gene are
      compared to reference standards in order to evaluate their potential clinical
      interest. MATERIAL AND METHODS: A solution of naked DNA bearing the hAAT gene was
      retrogradely injected in 7 pig livers using two different closed perfusion
      procedures: an endovascular catheterization-mediated procedure (n = 3) with
      infrahepatic inferior vena cava and portal vein blockage; and a surgery-mediated
      procedure (n = 4) with completely sealed liver. Gene transfer was performed
      through the suprahepatic inferior cava vein in the endovascular procedure and
      through the infrahepatic inferior vena cava in the surgical procedure. The
      efficiency of the procedures was evaluated 14 days after hydrofection by
      quantifying the hAAT protein copies per cell in tissue and in plasma. For
      comparison, samples from mice (n = 7) successfully hydrofected with hAAT and
      healthy human liver segments (n = 4) were evaluated. RESULTS: Gene decoding
      occurs efficiently using both procedures, with liver vascular arrest improving
      its efficiency. The surgically closed procedure (sealed organ) reached higher
      tissue protein levels (4x10^5- copies/cell) than the endovascular procedure,
      though the levels were lower than in human liver (5x10^6- copies/cell) and
      hydrofected mouse liver (10^6- copies/cell). However, protein levels in plasma
      were lower (p<0.001) than the reference standards in all cases. CONCLUSION:
      Hydrofection of hAAT DNA to "in vivo" isolated pig liver mediates highly
      efficient gene delivery and protein expression in tissue. Both endovascular and
      surgically closed models mediate high tissue protein expression. Impairment of
      protein secretion to plasma is observed and might be species-related. This study
      reinforces the potential application of closed liver hydrofection for therapeutic
      purposes, provided protein secretion improves.

PMID- 27695067
TI  - Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental
      Arthritis.
AB  - INTRODUCTION: Insulin like growth factor (IGF)-I can act on a variety of cells
      involved in cartilage and bone repair, yet IGF-I has not been studied extensively
      in the context of inflammatory arthritis. The objective of this study was to
      investigate whether IGF-I overexpression in the osteoblast lineage could lead to
      increased reparative or pathological bone formation in rheumatoid arthritis
      and/or spondyloarthritis respectively. METHODS: Mice overexpressing IGF-I in the
      osteoblast lineage (Ob-IGF-I+/-) line 324-7 were studied during collagen induced
      arthritis and in the DBA/1 aging model for ankylosing enthesitis. Mice were
      scored clinically and peripheral joints were analysed histologically for the
      presence of hypertrophic chondrocytes and osteocalcin positive osteoblasts.
      RESULTS: 90-100% of the mice developed CIA with no differences between the Ob-IGF
      I+/- and non-transgenic littermates. Histological analysis revealed similar
      levels of hypertrophic chondrocytes and osteocalcin positive osteoblasts in the
      ankle joints. In the DBA/1 aging model for ankylosing enthesitis 60% of the mice
      in both groups had a clinical score 1<. Severity was similar between both groups.
      Histological analysis revealed the presence of hypertrophic chondrocytes and
      osteocalcin positive osteoblasts in the toes in equal levels. CONCLUSION:
      Overexpression of IGF-I in the osteoblast lineage does not contribute to an
      increase in repair of erosions or syndesmophyte formation in mouse models for
      destructive and remodeling arthritis.

PMID- 27695068
TI  - Enhancing Predicted Efficacy of Tumor Treating Fields Therapy of Glioblastoma
      Using Targeted Surgical Craniectomy: A Computer Modeling Study.
AB  - OBJECTIVE: The present work proposes a new clinical approach to TTFields therapy
      of glioblastoma. The approach combines targeted surgical skull removal
      (craniectomy) with TTFields therapy to enhance the induced electrical field in
      the underlying tumor tissue. Using computer simulations, we explore the potential
      of the intervention to improve the clinical efficacy of TTFields therapy of brain
      cancer. METHODS: We used finite element analysis to calculate the electrical
      field distribution in realistic head models based on MRI data from two patients:
      One with left cortical/subcortical glioblastoma and one with deeply seated right
      thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions
      before and after virtual removal of bone areas of varying shape and size (10 to
      100 mm) immediately above the tumor. Field strength was evaluated before and
      after tumor resection to assess realistic clinical scenarios. RESULTS: For the
      superficial tumor, removal of a standard craniotomy bone flap increased the
      electrical field strength by 60-70% in the tumor. The percentage of tissue in
      expected growth arrest or regression was increased from negligible values to 30
      50%. The observed effects were highly focal and targeted at the regions of
      pathology underlying the craniectomy. No significant changes were observed in
      surrounding healthy tissues. Median field strengths in tumor tissue increased
      with increasing craniectomy diameter up to 50-70 mm. Multiple smaller burr holes
      were more efficient than single craniectomies of equivalent area. Craniectomy
      caused no significant field enhancement in the deeply seated tumor, but rather a
      focal enhancement in the brain tissue underlying the skull defect. CONCLUSIONS:
      Our results provide theoretical evidence that small and clinically feasible
      craniectomies may provide significant enhancement of TTFields intensity in
      cerebral hemispheric tumors without severely compromising brain protection or
      causing unacceptable heating in healthy tissues. A clinical trial is being
      planned to validate safety and efficacy.

PMID- 27695069
TI  - Differences in the Epidemiology of Childhood Infections with Avian Influenza A
      H7N9 and H5N1 Viruses.
AB  - The difference between childhood infections with avian influenza viruses A(H5N1)
      and A(H7N9) remains an unresolved but critically important question. We compared
      the epidemiological characteristics of 244 H5N1 and 41 H7N9 childhood cases (<15
      years old), as well as the childhood cluster cases of the two viruses. Our
      findings revealed a higher proportion of H5N1 than H7N9 childhood infections
      (31.1% vs. 6.4%, p = 0.000). However, the two groups did not differ significantly
      in age (median age: 5.0 vs. 5.5 y, p = 0.0651). The proportion of clustered cases
      was significantly greater among children infected with H5N1 than among children
      infected with H7N9 [46.7% (71/152) vs. 23.6% (13/55), p = 0.005], and most of the
      childhood cases were identified as secondary cases [46.4% (45/97) vs. 33.3%
      (10/30), p = 0.000]. Mild status accounted for 79.49% and 22.66%, severe status
      for 17.95% and 2.34%, and fatal cases for 2.56% and 75.00% of the H7N9 and H5N1
      childhood infection cases (all p<0.05), respectively. The fatality rates for the
      total, index and secondary childhood cluster cases were 52.86% (37/70), 88.5%
      (23/26) and 33.33% (15/45), respectively, in the H5N1 group, whereas no fatal
      H7N9 childhood cluster cases were identified. In conclusion, lower severity and
      greater transmission were found in the H7N9 childhood cases than in the H5N1
      childhood cases.

PMID- 27695066
TI  - A Novel Interaction between Tryptophan Hydroxylase 2 (TPH2) Gene Polymorphism
      (rs4570625) and BDNF Val66Met Predicts a High-Risk Emotional Phenotype in Healthy
      Subjects.
AB  - Poor inhibitory processing of negative emotional content is central to many
      psychiatric disorders, including depression and anxiety. Moreover, increasing
      evidence suggests that core aspects of emotion-inhibitory processing are largely
      inherited and as such may represent a key intermediate or risk-related phenotype
      for common affective diseases (e.g., unipolar depressive, anxiety disorders). The
      current study employed a candidate-gene approach in order to most effectively
      examine this complex behavioral phenotype. We examined the novel interaction
      between BDNF (Val66Met) and TPH2 (rs4570625) polymorphisms and their influence on
      behavioral inhibition of negative emotion in two independent investigations of
      healthy adults. BDNF Met carriers consistently report greater symptoms of
      affective disease and display corresponding behavioral rigidity, while TPH2 T
      carriers display poor inhibitory processing. These genotypes are traditionally
      perceived as 'risk' genotypes when compared to their respective major Val and G
      homozygous genotypes, but evidence is mixed. Recent studies in humans and mutant
      mouse models suggest biological epistasis between BDNF and genes involved in
      serotonin regulation. Moreover, polymorphisms in the TPH2 gene may have greater
      influence on serotonergic function than other more commonly studied polymorphisms
      (e.g., 5-HTTLPR). We observed consistent evidence across two different emotion
      inhibition paradigms, one with high internal validity (Study 1, n = 119) and one
      with high ecological validity (Study 2, n = 115) that the combination of Val/Val
      and G/G genotypes was clearly associated with impaired inhibition of negative
      emotional content. This was followed by individuals carrying the BDNF-Met allele
      (including Met/Val and Met/Met) when combined with the TPH2-T allele (including
      T/G and T/T combinations). The consistency of these results across tasks and
      studies suggests that these two groups may be particularly vulnerable to the most
      common psychiatric disorders and should be targets for future clinical
      investigation.

PMID- 27695070
TI  - Off-Road Vehicle Crash Risk during the Six Months after a Birthday.
AB  - BACKGROUND: Off-road vehicles are popular and thrilling for youth outside urban
      settings, yet sometimes result in a serious crash that requires emergency medical
      care. The relation between birthdays and the subsequent risk of an off-road
      vehicle crash is unknown. METHODS: We conducted a population-based before-and
      after longitudinal analysis of youth who received emergency medical care in
      Ontario, Canada, due to an off-road vehicle crash between April 1, 2002, and
      March 31, 2014. We identified youth injured in an off-road vehicle crash through
      population-based health-care databases of individuals treated for medical
      emergencies. We included youth aged 19 years or younger, distinguishing juniors
      (age <= 15 years) from juveniles (age >= 16 years). RESULTS: A total 32,777
      youths accounted for 35,202 emergencies due to off-road vehicle crashes within
      six months of their nearest birthday. Comparing the six months following a
      birthday to the six months prior to a birthday, crashes increased by about 2.7
      events per 1000 juniors (18.3 vs 21.0, p < 0.0001). The difference equaled a 15%
      increase in relative risk (95% confidence interval 12 to 18). The increase
      extended for months following a birthday, was not observed for traffic crashes
      due to on-road vehicles, and was partially explained by a lack of helmet wearing.
      As expected, off-road crash risks did not change significantly following a
      birthday among juveniles (19.2 vs 19.8, p = 0.61). CONCLUSIONS: Off-road vehicle
      crashes leading to emergency medical care increase following a birthday in youth
      below age 16 years. An awareness of this association might inform public health
      messages, gift-giving practices, age-related parental permissions, and prevention
      by primary care physicians.

PMID- 27695071
TI  - Differences between Practice Patterns of Conventional and Naturopathic GPs in
      Germany.
AB  - BACKGROUND: Limited evidence exists whether practice patterns of general
      practitioners (GPs) who have additionally completed training in naturopathy are
      different from those of conventional GPs. We aimed to assess and compare practice
      patterns of GPs in conventional and naturopathic GPs. METHODS: Routine data from
      41 GPs (31 with and 11 without additional qualification in NP, respectively) and
      180,789 patients, drawn from the CONTinuous morbidity registration Epidemiologic
      NeTwork (CONTENT)-registry and collected between 2009 and 2014, were used. To
      assess practice patterns determinants of (non-)phytopharmaceutical prescriptions,
      referrals and hospitalizations were analyzed using mixed-effects Poisson
      regression models. As explanatory variables, the qualification of the GP in NM,
      the age group and sex of the patient, as well as bivariate interactions between
      these variables were considered. RESULTS: GPs additionally qualified in
      naturopathy exhibited higher rates of phytopharmaceutical prescriptions (p<0.034;
      independent effect) compared to conventional GPs. This association was not
      observed with respect to non-phytopharmaceutical prescriptions. However,
      interaction effects between qualification and age group as well as sex were
      present with respect to both phytopharmaceutical and non-phytopharmaceutical
      prescriptions (all p<0.001). No further independent association existed between
      qualification and either referral rates or hospitalization rates, but again
      interactions between qualification and age group and sex (only referrals) were
      statistically significant (all p<0.0001). CONCLUSION: The results show that the
      rate of phyto-pharmaceutical prescriptions are generally higher when the GP has
      an additional qualification in naturopathy. Further differences in practice
      patterns between conventional and naturopathy GPs could be subject to certain age
      groups and sex. However, the magnitude of these differences seem to be rather
      small.

PMID- 27695073
TI  - Type of High School Predicts Academic Performance at University Better than
      Individual Differences.
AB  - Psychological correlates of academic performance have always been of high
      relevance to psychological research. The relation between psychometric
      intelligence and academic performance is one of the most consistent and well
      established findings in psychology. It is hypothesized that intelligence puts a
      limit on what an individual can learn or achieve. Moreover, a growing body of
      literature indicates a relationship between personality traits and academic
      performance. This relationship helps us to better understand how an individual
      will learn or achieve their goals. The aim of this study is to further
      investigate the relationship between psychological correlates of academic
      performance by exploring the potentially moderating role of prior education. The
      participants in this study differed in the type of high school they attended.
      They went either to gymnasium, a general education type of high school that
      prepares students specifically for university studies, or to vocational school,
      which prepares students both for the labour market and for further studies. In
      this study, we used archival data of psychological testing during career guidance
      in the final year of high school, and information about the university graduation
      of those who received guidance. The psychological measures included intelligence,
      personality and general knowledge. The results show that gymnasium students had
      greater chances of performing well at university, and that this relationship
      exceeds the contribution of intelligence and personality traits to university
      graduation. Moreover, psychological measures did not interact with type of high
      school, which indicates that students from different school types do not profit
      from certain individual characteristics.

PMID- 27695072
TI  - Image Restoration and Analysis of Influenza Virions Binding to Membrane Receptors
      Reveal Adhesion-Strengthening Kinetics.
AB  - With the development of single-particle tracking (SPT) microscopy and host
      membrane mimics called supported lipid bilayers (SLBs), stochastic virus-membrane
      binding interactions can be studied in depth while maintaining control over host
      receptor type and concentration. However, several experimental design challenges
      and quantitative image analysis limitations prevent the widespread use of this
      approach. One main challenge of SPT studies is the low signal-to-noise ratio of
      SPT videos, which is sometimes inevitable due to small particle sizes, low
      quantum yield of fluorescent dyes, and photobleaching. These situations could
      render current particle tracking software to yield biased binding kinetic data
      caused by intermittent tracking error. Hence, we developed an effective image
      restoration algorithm for SPT applications called STAWASP that reveals particles
      with a signal-to-noise ratio of 2.2 while preserving particle features. We tested
      our improvements to the SPT binding assay experiment and imaging procedures by
      monitoring X31 influenza virus binding to alpha2,3 sialic acid glycolipids. Our
      interests lie in how slight changes to the peripheral oligosaccharide structures
      can affect the binding rate and residence times of viruses. We were able to
      detect viruses binding weakly to a glycolipid called GM3, which was undetected
      via assays such as surface plasmon resonance. The binding rate was around 28
      folds higher when the virus bound to a different glycolipid called GD1a, which
      has a sialic acid group extending further away from the bilayer surface than GM3.
      The improved imaging allowed us to obtain binding residence time distributions
      that reflect an adhesion-strengthening mechanism via multivalent bonds. We
      empirically fitted these distributions using a time-dependent unbinding rate
      parameter, koff, which diverges from standard treatment of koff as a constant. We
      further explain how to convert these models to fit ensemble-averaged binding data
      obtained by assays such as surface plasmon resonance.

PMID- 27695074
TI  - Ncm, a Photolabile Group for Preparation of Caged Molecules: Synthesis and
      Biological Application.
AB  - Ncm, 6-nitrocoumarin-7-ylmethyl, is a photolabile protective group useful for
      making "caged" molecules. Ncm marries the reliable photochemistry of 2
      nitrobenzyl systems with the excellent stability and spectroscopic properties of
      the coumarin chromophore. From simple, commercially available starting materials,
      preparation of Ncm and its caged derivatives is both quick and easy. Photorelease
      of Ncm-caged molecules occurs on the microsecond time scale, with quantum
      efficiencies of 0.05-0.08. We report the synthesis and physical properties of Ncm
      and its caged derivatives. The utility of Ncm-caged glutamate for neuronal
      photostimulation is demonstrated in cultured hippocampal neurons and in brain
      slice preparations.

PMID- 27695076
TI  - Correction: Low Prevalence of Conjunctival Infection with Chlamydia trachomatis
      in a Treatment-Naive Trachoma-Endemic Region of the Solomon Islands.
AB  - [This corrects the article DOI: 10.1371/journal.pntd.0004863.].

PMID- 27695075
TI  - Risk Factors for Poor Adherence to Betaferon(r) Treatment in Patients with
      Relapsing-Remitting Multiple Sclerosis or Clinically Isolated Syndrome.
AB  - INTRODUCTION: Adherence to treatment, including early treatment discontinuation,
      in patients with multiple sclerosis or clinically isolated syndrome can be
      affected by: treatment tolerability, route of drug administration, patient age,
      disease duration, comorbidities, medical care, and support from their caregivers.
      AIM: This study aimed to identify the risk factors for poor adherence to
      Betaferon(r) treatment, including early discontinuation and omitting doses.
      MATERIALS AND METHODS: 852 adult patients treated with Betaferon participated in
      this 24-month study. All patients were interviewed using the Risk of Drop-out
      Questionnaire, the Center for Epidemiologic Studies Depression Scale and the
      Kurtzke Expanded Disability Status Scale. RESULTS: Patients who stopped therapy
      were younger (p = 0.003) had a higher mean EDSS score (p = 0.022), higher mean
      number of relapses (p = 0.017), and reported more often fear of injection (p =
      0.027) and adverse events (p = 0.007) than those who did not stop treatment.
      Comparing patients who stopped therapy in the first and the second year, patients
      who stopped therapy in the first year of treatment more frequently reported flu
      like symptoms and fever, and those who stopped therapy in the second year
      reported-ineffectiveness of treatment and disease progression. Multivariable
      logistic regression models confirmed that young age, short disease duration,
      advanced and progressing disease, and poor Betaferon tolerability were related to
      premature treatment discontinuation. The risk of omitting a dose during therapy
      was increased in patients who were working or studying, who had more advanced
      disease or more adverse events, and in patients who received less support from
      their caregivers. CONCLUSIONS: Several reasons may lead to problems with
      adherence to Betaferon treatment. Patients at higher risk of discontinuing
      treatment need to be identified early to make caregivers' support available to
      them.

PMID- 27695078
TI  - Enhancing Extraction of Drug-Drug Interaction from Literature Using Neutral
      Candidates, Negation, and Clause Dependency.
AB  - MOTIVATION: Supervised biomedical relation extraction plays an important role in
      biomedical natural language processing, endeavoring to obtain the relations
      between biomedical entities. Drug-drug interactions, which are investigated in
      the present paper, are notably among the critical biomedical relations. Thus far
      many methods have been developed with the aim of extracting DDI relations.
      However, unfortunately there has been a scarcity of comprehensive studies on the
      effects of negation, complex sentences, clause dependency, and neutral candidates
      in the course of DDI extraction from biomedical articles. RESULTS: Our study
      proposes clause dependency features and a number of features for identifying
      neutral candidates as well as negation cues and scopes. Furthermore, our
      experiments indicate that the proposed features significantly improve the
      performance of the relation extraction task combined with other kernel methods.
      We characterize the contribution of each category of features and finally
      conclude that neutral candidate features have the most prominent role among all
      of the three categories.

PMID- 27695077
TI  - Meta-Review of the Quantity and Quality of Evidence for Knee Arthroplasty
      Devices.
AB  - INTRODUCTION: Some cardiovascular devices are licensed based on limited evidence,
      potentially exposing patients to devices that are not safe or effective. Research
      is needed to ascertain if the same is true of other types of medical devices.
      Knee arthroplasty is a widely-used surgical procedure yet implant failures are
      not uncommon. The purpose of this study was to characterize available evidence on
      the safety and effectiveness of knee implants. METHODS: A review of primary
      studies included in health technology assessments (HTA) on total (TKA) and
      unicompartmental knee arthroplasty (UKA) was conducted. MEDLINE, EMBASE, CINAHL,
      Cochrane Library and Biotechnology & BioEngineering Abstracts were searched from
      2005 to 2014, plus journal tables of contents and 32 HTA web sites. Patients were
      aged 18 and older who underwent primary TKA or UKA assessed in cohort or
      randomized controlled studies. Summary statistics were used to report study
      characteristics. RESULTS: A total of 265 eligible primary studies published
      between 1986 and 2014 involving 59,217 patients were identified in 10 HTAs (2
      low, 7 moderate, 1 high risk of bias). Most evaluated TKA (198, 74.5%). The
      quality of evidence in primary studies was limited. Most studies were industry
      funded (23.8%) or offered no declaration of funding or conflict of interest
      (44.9%); based on uncontrolled single cohorts (58.5%), enrolled fewer than 100
      patients (66.4%), and followed patients for 2 years or less (UKA: single cohort
      29.8%, comparative cohort 16.7%, randomized trial 25.0%; TKA: single cohort
      25.0%, comparative cohort 31.4%, randomized trial 48.6%). Furthermore, most
      devices were evaluated in only one study (55.3% TKA implants, 61.1% UKA
      implants). CONCLUSIONS: Patients, physicians, hospitals and payers rely on poor
      quality evidence to support decisions about knee implants. Further research is
      needed to explore how decisions about the use of devices are currently made, and
      how the evidence base for device safety and effectiveness can be strengthened.

PMID- 27695079
TI  - Pretreatment Neutrophil to Lymphocyte Ratio Is Associated with Poor Survival in
      Patients with Stage I-III Non-Small Cell Lung Cancer.
AB  - BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been shown to be a
      prognostic indicator in several types of cancer. We aimed to investigate the
      association between NLR and survival in surgery-treated non-small cell lung
      cancer (NSCLC) patients. STUDY DESIGN: This large retrospective study included
      1,245 patients who underwent initial surgery for stage I-III NSCLC at The
      University of Texas MD Anderson Cancer Center between December 2002 and November
      2010. We analyzed the relationship of NLR with clinicopathological variables,
      local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS),
      recurrence-free survival (RFS), overall survival (OS), and disease-specific
      survival (DSS) in patients with high or low NLR using Kaplan-Meier method. Hazard
      ratios (HRs) with 95% confidence intervals (CIs) were used to assess the
      prognostic strength of NLR. RESULTS: There was a statistically significant
      association between the pretreatment NLR and histology type (P = 0.003) and tumor
      grade (P = 0.028). At a median follow-up time of 50.6 months, high NLR was
      associated with reduced DRFS (P = 0.011), OS (P < 0.0001) and DSS (P = 0.004); it
      was not associated with LRFS and RFS. Multivariable Cox analysis further revealed
      that NLR (P = 0.027), pathologic stage (P < 0.0001) and lymphovascular invasion
      (P < 0.0001) were strong independent predictors for DRFS. NLR was also an
      independent marker predicting poor OS (P = 0.002) and DSS (P = 0.017).
      CONCLUSION: The pretreatment NLR can serve as a biomarker to predict distant
      recurrence and death in stage I-III NSCLC patients. Combination of NLR and
      pathologic stage can better predict the OS and DSS in stage I-II NSCLC patients.

PMID- 27695082
TI  - Cheap Talk with Multiple Strategically Interacting Audiences: An Experimental
      Study.
AB  - We consider a cheap-talk setting that mimics the situation where an incumbent
      firm (the sender) is endowed with incentives to understate the true size of the
      market demand to two potential entrants (the receivers). Although our
      experimental data reveals that the senders' messages convey truthful information
      and this is picked up by the receivers, this overcommunication (relative to
      standard theoretical prediction) does not enhance efficient entry levels (and
      payoffs) to beyond what can be achieved without communication. The reason is that
      receivers fail to optimally translate the information received in their entry
      decision, possibly due to overcautiousness.

PMID- 27695081
TI  - Structural Basis of Mucopolysaccharidosis Type II and Construction of a Database
      of Mutant Iduronate 2-Sulfatases.
AB  - Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-linked genetic
      disorder caused by a deficiency of iduronate 2-sulfatase (IDS), and missense
      mutations comprising about 30% of the mutations responsible for MPS II result in
      heterogeneous phenotypes ranging from the severe to the attenuated form. To
      elucidate the basis of MPS II from the structural viewpoint, we built structural
      models of the wild type and mutant IDS proteins resulting from 131 missense
      mutations (phenotypes: 67 severe and 64 attenuated), and analyzed the influence
      of each amino acid substitution on the IDS structure by calculating the
      accessible surface area, the number of atoms affected and the root-mean-square
      distance. The results revealed that the amino acid substitutions causing MPS II
      were widely spread over the enzyme molecule and that the structural changes of
      the enzyme protein were generally larger in the severe group than in the
      attenuated one. Coloring of the atoms influenced by different amino acid
      substitutions at the same residue showed that the structural changes influenced
      the disease progression. Based on these data, we constructed a database of IDS
      mutations as to the structures of mutant IDS proteins.

PMID- 27695080
TI  - Amino Acid Permeases and Virulence in Cryptococcus neoformans.
AB  - Fungal opportunistic pathogens colonize various environments, from plants and
      wood to human and animal tissue. Regarding human pathogens, one great challenge
      during contrasting niche occupation is the adaptation to different conditions,
      such as temperature, osmolarity, salinity, pressure, oxidative stress and
      nutritional availability, which may constitute sources of stress that need to be
      tolerated and overcome. As an opportunistic pathogen, C. neoformans faces exactly
      these situations during the transition from the environment to the human host,
      encountering nutritional constraints. Our previous and current research on amino
      acid biosynthetic pathways indicates that amino acid permeases are regulated by
      the presence of the amino acids, nitrogen and temperature. Saccharomyces
      cerevisiae and Candida albicans have twenty-four and twenty-seven genes encoding
      amino acid permeases, respectively; conversely, they are scarce in number in
      Basidiomycetes (C. neoformans, Coprinopsis cinerea and Ustilago maydis), where
      nine to ten permease genes can be found depending on the species. In this study,
      we have demonstrated that two amino acid permeases are essential for virulence in
      C. neoformans. Our data showed that C. neoformans uses two global and redundant
      amino acid permeases, Aap4 and Aap5 to respond correctly to thermal and oxidative
      stress. Double deletion of these permeases causes growth arrest in C. neoformans
      at 37 degrees C and in the presence of hydrogen peroxide. The inability to uptake
      amino acid at a higher temperature and under oxidative stress also led to
      virulence attenuation in vivo. Our data showed that thermosensitivity caused by
      the lack of permeases Aap4 and Aap5 can be remedied by alkaline conditions
      (higher pH) and salinity. Permeases Aap4 and Aap5 are also required during
      fluconazole stress and they are the target of the plant secondary metabolite
      eugenol, a potent antifungal inhibitor that targets amino acid permeases. In
      summary, our work unravels (i) interesting physiological property of C.
      neoformans regarding its amino acid uptake system; (ii) an important aspect of
      virulence, which is the need for amino acid permeases during thermal and
      oxidative stress resistance and, hence, host invasion and colonization; and (iii)
      provides a convenient prototype for antifungal development, which are the amino
      acid permeases Aap4/Aap5 and their inhibitor.

PMID- 27695083
TI  - Th17 Cells Are More Protective Than Th1 Cells Against the Intracellular Parasite
      Trypanosoma cruzi.
AB  - Th17 cells are a subset of CD4+ T cells known to play a central role in the
      pathogenesis of many autoimmune diseases, as well as in the defense against some
      extracellular bacteria and fungi. However, Th17 cells are not believed to have a
      significant function against intracellular infections. In contrast to this
      paradigm, we have discovered that Th17 cells provide robust protection against
      Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas
      disease. Th17 cells confer significantly stronger protection against T. cruzi
      related mortality than even Th1 cells, traditionally thought to be the CD4+ T
      cell subset most important for immunity to T. cruzi and other intracellular
      microorganisms. Mechanistically, Th17 cells can directly protect infected cells
      through the IL-17A-dependent induction of NADPH oxidase, involved in the
      phagocyte respiratory burst response, and provide indirect help through IL-21
      dependent activation of CD8+ T cells. The discovery of these novel Th17 cell
      mediated direct protective and indirect helper effects important for
      intracellular immunity highlights the diversity of Th17 cell roles, and increases
      understanding of protective T. cruzi immunity, aiding the development of
      therapeutics and vaccines for Chagas disease.

PMID- 27695084
TI  - Bacterial Communities in the Rhizospheres of Three Mangrove Tree Species from
      Beilun Estuary, China.
AB  - The bacterial communities played important roles in the high productivity
      mangrove ecosystem. In this study, we investigated the vertical distributions of
      rhizosphere bacteria from three mangrove species (Bruguiera gymnorrhiza, Kandelia
      candel and Aegiceras corniculatum) in Beilun Estuary, China using high throughput
      DNA pyrosequencing of the 16S rRNA gene. Phylogenetic analysis showed that
      bacterial communities from mangrove rhizosphere sediments were dominated by
      Proteobacteria (mostly Deltaproteobacteria and Gammaproteobacteria), followed by
      Chloroflexi, Bacteroidetes, Planctomycetes and Acidobacteria. However, the ANOVA
      analysis on Shannon and Chao1 indices indicated that bacterial communities among
      sediments of the three mangrove species varied more strongly than the sampling
      depths. In addition, the PCA result demonstrated that the bacterial communities
      could be separated into three groups according to the mangrove species. Moreover,
      the dominated orders Rhodospirillales, GCA004 and envOPS12 were significantly
      different among sediments of the three mangrove species. The results of this
      study provided valuable information about the distribution feature of rhizosphere
      bacteria from Chinese mangrove plants and shed insights into biogeochemical
      transformations driven by bacteria in rhizosphere sediments.

PMID- 27695085
TI  - GM-CSF Down-Regulates TLR Expression via the Transcription Factor PU.1 in Human
      Monocytes.
AB  - Toll-like receptors (TLR) are crucial sensors of microbial agents such as
      bacterial or viral compounds. These receptors constitute key players in the
      induction of inflammation, e.g. in septic or chronic inflammatory diseases.
      Colony-stimulating factors (CSFs) such as granulocyte-macrophage-CSF (GM-CSF) or
      granulocyte-CSF (G-CSF) have been extensively investigated in their capacity to
      promote myelopoiesis in febrile neutropenia or to overcome immunosuppression in
      patients suffering from sepsis-associated neutropenia or from monocytic
      immunoincompetence. We report here that GM-CSF, downregulates TLR1, TLR2 and TLR4
      in a time- and dose-dependent fashion in human monocytes. Diminished pathogen
      recognition receptor expression was accompanied by reduced downstream p38 and
      extracellular-signal-regulated kinase (ERK) signaling upon lipoteichoic acid
      (LTA) and lipopolysaccharide (LPS) binding-and accordingly led to impaired
      proinflammatory cytokine production. Knockdown experiments of the transcription
      factors PU.1 and VentX showed that GM-CSF driven effects on TLR regulation is
      entirely PU.1 but not VentX dependent. We further analysed monocyte TLR and CD14
      expression upon exposure to the IMID(r) immunomodulatory drug Pomalidomide (CC
      4047), a Thalidomide analogue known to downregulate PU.1. Indeed, Pomalidomide in
      part reversed the GM-CSF-mediated effects. Our data indicate a critical role of
      PU.1 in the regulation of TLR1, 2, 4 and of CD14, thus targeting PU.1 ultimately
      results in TLR modulation. The PU.1 mediated immunomodulatory properties of GM
      CSF should be taken into consideration upon usage of GM-CSF in inflammatory or
      infection-related conditions.

PMID- 27695086
TI  - Performance of the Malay Audit of Diabetes Dependent Quality of Life-18 and
      Associates of Quality of Life among Patients with Type 2 Diabetes Mellitus from
      Major Ethnic Groups of Malaysia.
AB  - INTRODUCTION: Diabetes Mellitus (DM) is notorious for its metabolic effect, acute
      and chronic complications and impact on Quality of Life (QoL). Successful
      intervention to improve QoL necessitates a valid and reliable measurement tool to
      identify areas of concern to patients with diabetes. OBJECTIVES: To (1) assess
      the factor structure of the Malay Audit of Diabetes Dependent Quality of Life-18
      (ADDQoL-18) questionnaire; (2) determine the impact of DM on QoL; and (3)
      identify areas of concern to patients with type 2 DM from three major ethnic
      groups in Malaysia. METHODS: Data was obtained from a cross sectional study
      involving 256 patients with type 2 DM attending the diabetes clinic of the
      National University of Malaysia Medical Centre. The Malay version of ADDQoL-18
      survey was translated from its English version according to standard guidelines
      and administered by a trained research assistant. Exploratory Factor Analysis
      (EFA) with oblimin rotation was used to determine factor structure of the data.
      Confirmatory Factor Analysis (CFA) was used to confirm the factor structure.
      Hierarchical liner regression was used to determine factors associated with QoL.
      RESULTS: Unforced factor solution yielded two factors for the whole sample.
      Forced one factor solution was ascertained for the whole sample and for each
      ethnic group. Loadings ranged between 0.588 and 0.949. Reliability coefficients
      were all higher than 0.955. CFA showed that the two factor model had better fit
      statistics. QoL was associated with the use of insulin and desired glycaemic
      control, longer diabetes duration, worry about diabetes, and diabetes
      complications. CONCLUSIONS: The Malay ADDQoL-18 is a valid tool to be used among
      patients with diabetes from different ethnic groups in Malaysia. The use of
      insulin to achieve desired glycaemic control had more negative impact on QoL than
      the use of tablets and/or dietary changes.

PMID- 27695087
TI  - Production, Quality Control, Stability and Pharmacotoxicity of a Malaria Vaccine
      Comprising Three Highly Similar PfAMA1 Protein Molecules to Overcome Antigenic
      Variation.
AB  - Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading asexual
      blood stage vaccine candidate for malaria. In preparation for clinical trials,
      three Diversity Covering (DiCo) PfAMA1 ectodomain proteins, designed to overcome
      the intrinsic polymorphism that is present in PfAMA1, were produced under Good
      Manufacturing Practice (GMP) in Pichia pastoris. Using identical methodology, the
      3 strains were cultivated in 70-L scale fed-batch fermentations and PfAMA1-DiCos
      were purified by two chromatography steps, an ultrafiltration/diafiltration
      procedure and size exclusion chromatography, resulting in highly pure (>95%)
      PfAMA1-DiCo1, PfAMA1 DiCo2 and PfAMA1 DiCo3, with final yields of 1.8, 1.9 and
      1.3 gram, respectively. N-terminal determinations showed that approximately 50%
      of each of the proteins lost 12 residues from their N-terminus, in accordance
      with SDS-PAGE (2 main bands) and MS-data. Under reducing conditions a site of
      limited proteolytic cleavage within a disulphide bonded region became evident.
      The three proteins quantitatively bound to the mAb 4G2 that recognizes a
      conformational epitope, suggesting proper folding of the proteins. The
      lyophilized Drug Product (1:1:1 mixture of PfAMA1-DiCo1, DiCo2, DiCo3) fulfilled
      all pre-set release criteria (appearance, dissolution rate, identity, purity,
      protein content, moisture content, sub-visible particles, immuno-potency (after
      reconstitution with adjuvant), abnormal toxicity, sterility and endotoxin), was
      stable in accelerated and real-time stability studies at -20 degrees C for over
      24 months. When formulated with adjuvants selected for clinical phase I
      evaluation, the Drug Product did not show adverse effect in a repeated-dose
      toxicity study in rabbits. The Drug Product has entered a phase Ia/Ib clinical
      trial.

PMID- 27695088
TI  - Vaccine Strain-Specificity of Protective HLA-Restricted Class 1 P. falciparum
      Epitopes.
AB  - A DNA prime/adenovirus boost malaria vaccine encoding Plasmodium falciparum
      strain 3D7 CSP and AMA1 elicited sterile clinical protection associated with CD8+
      T cell interferon-gamma (IFN-gamma) cells responses directed to HLA class 1
      restricted AMA1 epitopes of the vaccine strain 3D7. Since a highly effective
      malaria vaccine must be broadly protective against multiple P. falciparum
      strains, we compared these AMA1 epitopes of two P. falciparum strains (7G8 and
      3D7), which differ by single amino acid substitutions, in their ability to recall
      CD8+ T cell activities using ELISpot and flow cytometry/intracellular staining
      assays. The 7G8 variant peptides did not recall 3D7 vaccine-induced CD8+ T IFN
      gamma cell responses in these assays, suggesting that protection may be limited
      to the vaccine strain. The predicted MHC binding affinities of the 7G8 variant
      epitopes were similar to the 3D7 epitopes, suggesting that the amino acid
      substitutions of the 7G8 variants may have interfered with TCR recognition of the
      MHC:peptide complex or that the 7G8 variant may have acted as an altered peptide
      ligand. These results stress the importance of functional assays in defining
      protective epitopes. Clinical Trials Registrations: NCT00870987, NCT00392015.

PMID- 27695089
TI  - No Compensatory Relationship between the Innate and Adaptive Immune System in
      Wild-Living European Badgers.
AB  - The innate immune system provides the primary vertebrate defence system against
      pathogen invasion, but it is energetically costly and can have immune
      pathological effects. A previous study in sticklebacks found that intermediate
      major histocompatibility complex (MHC) diversity correlated with a lower
      leukocyte coping capacity (LCC), compared to individuals with fewer, or many, MHC
      alleles. The organization of the MHC genes in mammals, however, differs to the
      highly duplicated MHC genes in sticklebacks by having far fewer loci. Using
      European badgers (Meles meles), we therefore investigated whether innate immune
      activity, estimated functionally as the ability of an individual's leukocytes to
      produce a respiratory burst, was influenced by MHC diversity. We also
      investigated whether LCC was influenced by factors such as age-class, sex, body
      condition, season, year, neutrophil and lymphocyte counts, and intensity of
      infection with five different pathogens. We found that LCC was not associated
      with specific MHC haplotypes, MHC alleles, or MHC diversity, indicating that the
      innate immune system did not compensate for the adaptive immune system even when
      there were susceptible MHC alleles/haplotypes, or when the MHC diversity was low.
      We also identified a seasonal and annual variation of LCC. This temporal
      variation of innate immunity was potentially due to physiological trade-offs or
      temporal variation in pathogen infections. The innate immunity, estimated as LCC,
      does not compensate for MHC diversity suggests that the immune system may
      function differently between vertebrates with different MHC organizations, with
      implications for the evolution of immune systems in different taxa.

PMID- 27695090
TI  - Proteomic Analysis of Outer Membrane Proteins from Salmonella Enteritidis Strains
      with Different Sensitivity to Human Serum.
AB  - Differential analysis of outer membrane composition of S. Enteritidis strains,
      resistant to 50% normal human serum (NHS) was performed in order to find factors
      influencing the resistance to higher concentrations of NHS. Ten S. Enteritidis
      clinical strains, resistant to 50% NHS, all producing very long
      lipopolysaccharide, were subjected to the challenge of 75% NHS. Five extreme
      strains: two resistant and three sensitive to 75% NHS, were chosen for the
      further analysis of outer membrane proteins composition. Substantial differences
      were found in the levels of particular outer membrane proteins between resistant
      and sensitive strains, i.e. outer membrane protease E (PgtE) was present mainly
      in resistant strains, while sensitive strains possessed a high level of flagellar
      hook-associated protein 2 (FliD) and significantly higher levels of outer
      membrane protein A (OmpA).

PMID- 27695091
TI  - CERAMIC: Case-Control Association Testing in Samples with Related Individuals,
      Based on Retrospective Mixed Model Analysis with Adjustment for Covariates.
AB  - We consider the problem of genetic association testing of a binary trait in a
      sample that contains related individuals, where we adjust for relevant covariates
      and allow for missing data. We propose CERAMIC, an estimating equation approach
      that can be viewed as a hybrid of logistic regression and linear mixed-effects
      model (LMM) approaches. CERAMIC extends the recently proposed CARAT method to
      allow samples with related individuals and to incorporate partially missing data.
      In simulations, we show that CERAMIC outperforms existing LMM and generalized LMM
      approaches, maintaining high power and correct type 1 error across a wider range
      of scenarios. CERAMIC results in a particularly large power increase over
      existing methods when the sample includes related individuals with some missing
      data (e.g., when some individuals with phenotype and covariate information have
      missing genotype), because CERAMIC is able to make use of the relationship
      information to incorporate partially missing data in the analysis while
      correcting for dependence. Because CERAMIC is based on a retrospective analysis,
      it is robust to misspecification of the phenotype model, resulting in better
      control of type 1 error and higher power than that of prospective methods, such
      as GMMAT, when the phenotype model is misspecified. CERAMIC is computationally
      efficient for genomewide analysis in samples of related individuals of almost any
      configuration, including small families, unrelated individuals and even large,
      complex pedigrees. We apply CERAMIC to data on type 2 diabetes (T2D) from the
      Framingham Heart Study. In a genome scan, 9 of the 10 smallest CERAMIC p-values
      occur in or near either known T2D susceptibility loci or plausible candidates,
      verifying that CERAMIC is able to home in on the important loci in a genome scan.

PMID- 27695093
TI  - Association between Peer Cigarette Smoking and Electronic Cigarette Smoking among
      Adolescent Nonsmokers: A National Representative Survey.
AB  - We assessed the association between electronic cigarette (e-cigarette) use and
      peer cigarette smoking, a major risk factor for the initiation of cigarette
      smoking in adolescents. Data from the 2013 Korea Youth Risk Behavior Web-based
      Survey of 65,753 nonsmokers aged 13-18 years were analyzed using multiple
      logistic regression. A total of 3.8% of the Korean adolescents were 'ever e
      cigarette' users and 1.2% were current users. Adjusted odds ratios (ORs) for
      current and ever e-cigarette use compared to those whose closest friends were non
      smokers ranged from 2.05 (95% confidence interval [CI], 1.82-2.30) to 5.50 (95%
      CI, 4.77-6.34), and from 2.23 (95% CI, 1.77-2.81) to 7.82 (95% CI, 5.97-10.25)
      for those who had 'some' close friends to 'most/all' friends who smoked,
      respectively. The slopes of the adjusted ORs for e-cigarette use in 'never
      smokers' were more than twice as steep as those in 'former smokers', showing a
      significant interaction effect between the proportion of smoking closest friends
      and cigarette smoking status (never or former smokers) (p<0.001 for interaction).
      Peer cigarette smoking had a significant association with e-cigarette use in
      adolescent nonsmokers, and this association was greater on never smokers than
      former smokers.

PMID- 27695092
TI  - Overexpression of Ribosomal RNA in the Development of Human Cervical Cancer Is
      Associated with rDNA Promoter Hypomethylation.
AB  - The ribosomal RNA (rRNA) gene encodes rRNA for protein synthesis. Aberrant
      expression of the rRNA gene has been generally observed in tumor cells and levels
      of its promoter methylation as an epigenetic regulator affect rRNA gene
      transcription. The possible relationship between expression and promoter
      methylation of rDNA has not been examined in human clinical cervical cancer. Here
      we investigate rRNA gene expression by quantitative real time PCR, and promoter
      methylation levels by HpaII/MspI digestion and sodium bisulfite sequencing in the
      development of human cervical cancer. We find that indeed rRNA levels are
      elevated in most of cervical intraepithelial neoplasia (CIN) specimens as
      compared with non-cancer tissues. The rDNA promoter region in cervical
      intraepithelial neoplasia (CIN) tissues reveals significant hypomethylation at
      cytosines in the context of CpG dinucleotides, accompanied with rDNA chromatin
      decondensation. Furthermore treatment of HeLa cells with the methylation
      inhibitor drug 5-aza-2'-deoxycytidine (DAC) demonstrates the negative correlation
      between the expression of 45S rDNA and the methylation level in the rDNA promoter
      region. These data suggest that a decrease in rDNA promoter methylation levels
      can result in an increase of rRNA synthesis in the development of human cervical
      cancer.

PMID- 27695094
TI  - Estimating Common Growth Patterns in Juvenile Chinook Salmon (Oncorhynchus
      tshawytscha) from Diverse Genetic Stocks and a Large Spatial Extent.
AB  - Life history variation in Pacific salmon (Oncorhynchus spp.) supports species
      resilience to natural disturbances and fishery exploitation. Within salmon
      species, life-history variation often manifests during freshwater and estuarine
      rearing, as variation in growth. To date, however, characterizing variability in
      growth patterns within and among individuals has been difficult via conventional
      sampling methods because of the inability to obtain repeated size measurements.
      In this study we related otolith microstructures to growth rates of individual
      juvenile Chinook salmon (O. tshawytscha) from the Columbia River estuary over a
      two-year period (2010-2012). We used dynamic factor analysis to determine whether
      there were common patterns in growth rates within juveniles based on their natal
      region, capture location habitat type, and whether they were wild or of hatchery
      origin. We identified up to five large-scale trends in juvenile growth rates
      depending on month and year of capture. We also found that hatchery fish had a
      narrower range of trend loadings for some capture groups, suggesting that
      hatchery fish do not express the same breadth of growth variability as wild fish.
      However, we were unable to resolve a relationship between specific growth
      patterns and habitat transitions. Our study exemplifies how a relatively new
      statistical analysis can be applied to dating or aging techniques to summarize
      individual variation, and characterize aspects of life history diversity.

PMID- 27695095
TI  - The Prevalence of and Risk Factors Associated with Musculoskeletal Disorders
      among Sonographers in Central China: A Cross-Sectional Study.
AB  - OBJECTIVE: Studies from industrialized countries show that musculoskeletal
      disorders (MSD) occur commonly in sonographers. However, little is known about
      sonographers in China, where the awareness of ergonomics and MSD, workload, and
      available equipment/facilities may differ. We aimed to investigate the prevalence
      of MSD and associated risk factors in sonographers in central China. METHODS: A
      cross-sectional survey was conducted with 381 sonographers from 14 randomly
      selected tertiary hospitals in Hubei province, central China. Musculoskeletal
      symptoms (using the Nordic Questionnaire) and risk factors (mostly derived from
      the Health Benefit Trust survey instrument and the Dutch Musculoskeletal
      Questionnaire) were recorded. Multivariate logistic regression was used to
      quantify associations between risk factors and MSD. RESULTS: The 12-month period
      prevalence of MSD was 98.3%, being highest in the neck (93.5%) and shoulder
      (92.2%), followed by the lower back (83.2%), wrist/hand, upper back, and elbow.
      Factors contributing to neck pain were psychological fatigue, shoulder abduction
      and trunk bend-and-twist posture. Height-adjustable tables and chairs were
      protective factors. Shoulder pain was associated with female sex, health status,
      mental stress, shoulder abduction, and trunk bend-and-twist posture. Height
      adjustable chairs and the awareness of adjusting the workstation before scanning
      were protective factors. Elbow pain was associated with health status and height
      adjustable tables. Wrist/hand pain was associated with female sex, bending the
      wrist, and working with obese patients. Upper back pain was associated with
      shoulder abduction, height-adjustable chairs, and device location. Lower back
      pain was associated with the number of scans performed per day, awkward postures,
      bending the trunk, twisting or bending the neck forward, and using a footrest.
      CONCLUSIONS: This study suggests a high prevalence of MSD in sonographers in
      central China. Hence, it is necessary to improve the awareness of MSD by
      training, and the ergonomics of their current work environment by addressing
      physical workload, and psychological and equipment/facility-related factors.

PMID- 27695097
TI  - Minimal Residual Disease at First Achievement of Complete Remission Predicts
      Outcome in Adult Patients with Philadelphia Chromosome-Negative Acute
      Lymphoblastic Leukemia.
AB  - We evaluated the prognostic effect of minimal residual disease at first
      achievement of complete remission (MRD at CR1) in adult patients with
      Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). A total of
      97 patients received treatment in our center between 2007 and 2012 were
      retrospectively reviewed in this study. Patients were divided into two arms
      according to the post-remission therapy (chemotherapy alone or allogeneic
      hematopoietic stem cell transplantation (allo-HSCT)) they received. MRD was
      detected by four-color flow cytometry. We chose 0.02% and 0.2% as the cut-off
      points of MRD at CR1 for risk stratification using receiver operating
      characteristic analysis. The 3-year overall survival (OS) and leukemia free
      survival (LFS) rates for the whole cohort were 46.2% and 40.5%. MRD at CR1 had a
      significantly negative correlation with survival in both arms. Three-year OS
      rates in the chemotherapy arm were 70.0%, 25.2%, 0% (P = 0.003) for low,
      intermediate, and high levels of MRD at CR1, respectively. Three-year OS rates in
      the transplant arm were 81.8%, 64.3%, 27.3% (P = 0.005) for low, intermediate,
      and high levels of MRD at CR1, respectively. Multivariate analysis confirmed that
      higher level of MRD at CR1 was a significant adverse factor for OS and LFS.
      Compared with chemotherapy alone, allo-HSCT significantly improved LFS rates in
      patients with intermediate (P = 0.005) and high (P = 0.022) levels of MRD at CR1,
      but not patients with low level of MRD at CR1 (P = 0.851). These results
      suggested that MRD at CR1 could strongly predict the outcome of adult ALL.
      Patients with intermediate and high levels of MRD at CR1 would benefit from allo
      HSCT.

PMID- 27695096
TI  - Detection of Leptomeningeal Metastasis by Contrast-Enhanced 3D T1-SPACE:
      Comparison with 2D FLAIR and Contrast-Enhanced 2D T1-Weighted Images.
AB  - INTRODUCTION: To compare the diagnostic accuracy of contrast-enhanced
      3D(dimensional) T1-weighted sampling perfection with application-optimized
      contrasts by using different flip angle evolutions (T1-SPACE), 2D fluid
      attenuated inversion recovery (FLAIR) images and 2D contrast-enhanced T1-weighted
      image in detection of leptomeningeal metastasis except for invasive procedures
      such as a CSF tapping. MATERIALS AND METHODS: Three groups of patients were
      included retrospectively for 9 months (from 2013-04-01 to 2013-12-31). Group 1
      patients with positive malignant cells in CSF cytology (n = 22); group 2, stroke
      patients with steno-occlusion in ICA or MCA (n = 16); and group 3, patients with
      negative results on MRI, whose symptom were dizziness or headache (n = 25). A
      total of 63 sets of MR images are separately collected and randomly arranged: (1)
      CE 3D T1-SPACE; (2) 2D FLAIR; and (3) CE T1-GRE using a 3-Tesla MR system. A
      faculty neuroradiologist with 8-year-experience and another 2nd grade trainee in
      radiology reviewed each MR image- blinded by the results of CSF cytology and
      coded their observations as positives or negatives of leptomeningeal metastasis.
      The CSF cytology result was considered as a gold standard. Sensitivity and
      specificity of each MR images were calculated. Diagnostic accuracy was compared
      using a McNemar's test. A Cohen's kappa analysis was performed to assess inter
      observer agreements. RESULTS: Diagnostic accuracy was not different between 3D T1
      SPACE and CSF cytology by both raters. However, the accuracy test of 2D FLAIR and
      2D contrast-enhanced T1-weighted GRE was inconsistent by the two raters. The
      Kappa statistic results were 0.657 (3D T1-SPACE), 0.420 (2D FLAIR), and 0.160 (2D
      contrast-enhanced T1-weighted GRE). The 3D T1-SPACE images showed the highest
      inter-observer agreements between the raters. CONCLUSIONS: Compared to 2D FLAIR
      and 2D contrast-enhanced T1-weighted GRE, contrast-enhanced 3D T1 SPACE showed a
      better detection rate of leptomeningeal metastasis.

PMID- 27695099
TI  - Correction: Effects of Aging on Genioglossus Motor Units in Humans.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0104572.].

PMID- 27695098
TI  - Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis
      Promotes Angiogenesis in Endometriosis.
AB  - Endometriosis is characterized by the ectopic development of the endometrium
      which relies on angiogenesis. Although studies have identified the involvement of
      different matrix metalloproteinases (MMPs) in endometriosis, no study has yet
      investigated the role of MMP-2 in endometriosis-associated angiogenesis. The
      present study aims to understand the regulation of MMP-2 activity in endothelial
      cells and on angiogenesis during progression of ovarian endometriosis.
      Histological and biochemical data showed increased expressions of vascular
      endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von
      Willebrand factor along with angiogenesis during endometriosis progression. Women
      with endometriosis showed decreased MMP-2 activity in eutopic endometrium as
      compared to women without endometriosis. However, ectopic ovarian endometrioma
      showed significantly elevated MMP-2 activity with disease severity. In addition,
      increased MT1MMP and decreased tissue inhibitors of metalloproteinases (TIMP)-2
      expressions were found in the late stages of endometriosis indicating more MMP-2
      activation with disease progression. In vitro study using human endothelial cells
      showed that prostaglandin E2 (PGE2) significantly increased MMP-2 activity as
      well as tube formation. Inhibition of COX-2 and/or phosphorylated AKT suppressed
      MMP-2 activity and endothelial tube formation suggesting involvement of PGE2 in
      regulation of MMP-2 activity during angiogenesis. Moreover, specific inhibition
      of MMP-2 by chemical inhibitor significantly reduced cellular migration, invasion
      and tube formation. In ovo assay showed decreased angiogenic branching upon MMP-2
      inhibition. Furthermore, a significant reduction of lesion numbers was observed
      upon inhibition of MMP-2 and COX-2 in mouse model of endometriosis. In
      conclusion, our study establishes the involvement of MMP-2 activity via COX-2
      PGE2-pAKT axis in promoting angiogenesis during endometriosis progression.

PMID- 27695100
TI  - Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells
      in an Ex Vivo Human Skin Model.
AB  - Borrelia burgdorferi is transmitted into the skin of the host where it encounters
      and interacts with two dendritic cell (DC) subsets; Langerhans cells (LCs) and
      dermal DCs (DDCs). These cells recognize pathogens via pattern recognition
      receptors, mature and migrate out of the skin into draining lymph nodes, where
      they orchestrate adaptive immune responses. In order to investigate the response
      of skin DCs during the early immunopathogenesis of Lyme borreliosis, we injected
      B. burgdorferi intradermally into full-thickness human skin and studied the
      migration of DCs out of the skin, the activation profile and phenotype of
      migrated cells. We found a significant increase in the migration of LCs and DDCs
      in response to B. burgdorferi. Notably, migration was prevented by blocking TLR2.
      DCs migrated from skin inoculated with higher numbers of spirochetes expressed
      significantly higher levels of CD83 and produced pro-inflammatory cytokines. No
      difference was observed in the expression of HLA-DR, CD86, CD38, or CCR7. To
      conclude, we have established an ex vivo human skin model to study DC-B.
      burgdorferi interactions. Using this model, we have demonstrated that B.
      burgdorferi-induced DC migration is mediated by TLR2. Our findings underscore the
      utility of this model as a valuable tool to study immunity to spirochetal
      infections.

PMID- 27695102
TI  - Reflectance Prediction Modelling for Residual-Based Hyperspectral Image Coding.
AB  - A Hyperspectral (HS) image provides observational powers beyond human vision
      capability but represents more than 100 times the data compared to a traditional
      image. To transmit and store the huge volume of an HS image, we argue that a
      fundamental shift is required from the existing "original pixel intensity"-based
      coding approaches using traditional image coders (e.g., JPEG2000) to the
      "residual"-based approaches using a video coder for better compression
      performance. A modified video coder is required to exploit spatial-spectral
      redundancy using pixel-level reflectance modelling due to the different
      characteristics of HS images in their spectral and shape domain of panchromatic
      imagery compared to traditional videos. In this paper a novel coding framework
      using Reflectance Prediction Modelling (RPM) in the latest video coding standard
      High Efficiency Video Coding (HEVC) for HS images is proposed. An HS image
      presents a wealth of data where every pixel is considered a vector for different
      spectral bands. By quantitative comparison and analysis of pixel vector
      distribution along spectral bands, we conclude that modelling can predict the
      distribution and correlation of the pixel vectors for different bands. To exploit
      distribution of the known pixel vector, we estimate a predicted current spectral
      band from the previous bands using Gaussian mixture-based modelling. The
      predicted band is used as the additional reference band together with the
      immediate previous band when we apply the HEVC. Every spectral band of an HS
      image is treated like it is an individual frame of a video. In this paper, we
      compare the proposed method with mainstream encoders. The experimental results
      are fully justified by three types of HS dataset with different wavelength
      ranges. The proposed method outperforms the existing mainstream HS encoders in
      terms of rate-distortion performance of HS image compression.

PMID- 27695101
TI  - Transcriptome Dynamics during Maize Endosperm Development.
AB  - The endosperm is a major organ of the seed that plays vital roles in determining
      seed weight and quality. However, genome-wide transcriptome patterns throughout
      maize endosperm development have not been comprehensively investigated to date.
      Accordingly, we performed a high-throughput RNA sequencing (RNA-seq) analysis of
      the maize endosperm transcriptome at 5, 10, 15 and 20 days after pollination
      (DAP). We found that more than 11,000 protein-coding genes underwent alternative
      splicing (AS) events during the four developmental stages studied. These genes
      were mainly involved in intracellular protein transport, signal transmission,
      cellular carbohydrate metabolism, cellular lipid metabolism, lipid biosynthesis,
      protein modification, histone modification, cellular amino acid metabolism, and
      DNA repair. Additionally, 7,633 genes, including 473 transcription factors (TFs),
      were differentially expressed among the four developmental stages. The
      differentially expressed TFs were from 50 families, including the bZIP, WRKY,
      GeBP and ARF families. Further analysis of the stage-specific TFs showed that
      binding, nucleus and ligand-dependent nuclear receptor activities might be
      important at 5 DAP, that immune responses, signalling, binding and lumen
      development are involved at 10 DAP, that protein metabolic processes and the
      cytoplasm might be important at 15 DAP, and that the responses to various stimuli
      are different at 20 DAP compared with the other developmental stages. This RNA
      seq analysis provides novel, comprehensive insights into the transcriptome
      dynamics during early endosperm development in maize.

PMID- 27695103
TI  - In Vivo Imaging Reveals Composite Coding for Diagonal Motion in the Drosophila
      Visual System.
AB  - Understanding information coding is important for resolving the functions of
      visual neural circuits. The motion vision system is a classic model for studying
      information coding as it contains a concise and complete information-processing
      circuit. In Drosophila, the axon terminals of motion-detection neurons (T4 and
      T5) project to the lobula plate, which comprises four regions that respond to the
      four cardinal directions of motion. The lobula plate thus represents a
      topographic map on a transverse plane. This enables us to study the coding of
      diagonal motion by investigating its response pattern. By using in vivo two
      photon calcium imaging, we found that the axon terminals of T4 and T5 cells in
      the lobula plate were activated during diagonal motion. Further experiments
      showed that the response to diagonal motion is distributed over the following two
      regions compared to the cardinal directions of motion-a diagonal motion selective
      response region and a non-selective response region-which overlap with the
      response regions of the two vector-correlated cardinal directions of motion.
      Interestingly, the sizes of the non-selective response regions are linearly
      correlated with the angle of the diagonal motion. These results revealed that the
      Drosophila visual system employs a composite coding for diagonal motion that
      includes both independent coding and vector decomposition coding.

PMID- 27695105
TI  - Using the Fusion Proximal Area Method and Gravity Method to Identify Areas with
      Physician Shortages.
AB  - OBJECTIVES: This paper presents a geographic information system (GIS)-based
      proximal area method and gravity method for identifying areas with physician
      shortages. The innovation of this paper is that it uses the appropriate methods
      to discover each type of health resource and then integrates all these methods to
      assess spatial access to health resources using population distribution data. In
      this way, spatial access to health resources for an entire city can be visualized
      in one neat package, which can help health policy makers quickly comprehend
      realistic distributions of health resources at a macro level. METHODS: First,
      classify health resources according to the trade areas of the patients they
      serve. Second, apply an appropriate method to each different type of health
      resource to measure spatial access to those resources. Third, integrate all types
      of access using population distribution data. RESULTS: In case study of Shanghai
      with the fusion method, areas with physician shortages are located primarily in
      suburban districts, especially in district junction areas. The result suggests
      that the government of Shanghai should pay more attention to these areas by
      investing in new or relocating existing health resources. CONCLUSION: The fusion
      method is demonstrated to be more accurate and practicable than using a single
      method to assess spatial access to health resources.

PMID- 27695104
TI  - Are Categorical Spatial Relations Encoded by Shifting Visual Attention between
      Objects?
AB  - Perceiving not just values, but relations between values, is critical to human
      cognition. We tested the predictions of a proposed mechanism for processing
      categorical spatial relations between two objects-the shift account of relation
      processing-which states that relations such as 'above' or 'below' are extracted
      by shifting visual attention upward or downward in space. If so, then shifts of
      attention should improve the representation of spatial relations, compared to a
      control condition of identity memory. Participants viewed a pair of briefly
      flashed objects and were then tested on either the relative spatial relation or
      identity of one of those objects. Using eye tracking to reveal participants'
      voluntary shifts of attention over time, we found that when initial fixation was
      on neither object, relational memory showed an absolute advantage for the object
      following an attention shift, while identity memory showed no advantage for
      either object. This result is consistent with the shift account of relation
      processing. When initial fixation began on one of the objects, identity memory
      strongly benefited this fixated object, while relational memory only showed a
      relative benefit for objects following an attention shift. This result is also
      consistent, although not as uniquely, with the shift account of relation
      processing. Taken together, we suggest that the attention shift account provides
      a mechanistic explanation for the overall results. This account can potentially
      serve as the common mechanism underlying both linguistic and perceptual
      representations of spatial relations.

PMID- 27695106
TI  - FMRP Associates with Cytoplasmic Granules at the Onset of Meiosis in the Human
      Oocyte.
AB  - Germ cell development and primordial follicle formation during fetal life is
      critical in establishing the pool of oocytes that subsequently determines the
      reproductive lifespan of women. Fragile X-associated primary ovarian
      insufficiency (FXPOI) is caused by inheritance of the FMR1 premutation allele and
      approximately 20% of women with the premutation allele develop ovarian
      dysfunction and premature ovarian insufficiency. However, the underlying disease
      mechanism remains obscure, and a potential role of FMRP in human ovarian
      development has not been explored. We have characterised the expression of FMR1
      and FMRP in the human fetal ovary at the time of germ cell entry into meiosis
      through to primordial follicle formation. FMRP expression is exclusively in germ
      cells in the human fetal ovary. Increased FMRP expression in germ cells coincides
      with the loss of pluripotency-associated protein expression, and entry into
      meiosis is associated with FMRP granulation. In addition, we have uncovered FMRP
      association with components of P-bodies and stress granules, suggesting it may
      have a role in mRNA metabolism at the time of onset of meiosis. Therefore, this
      data support the hypothesis that FMRP plays a role regulating mRNAs during
      pivotal maturational processes in fetal germ cells, and ovarian dysfunction
      resulting from FMR1 premutation may have its origins during these stages of
      oocyte development.

PMID- 27695108
TI  - Mycorrhizal Fungal Diversity and Community Composition in Two Closely Related
      Platanthera (Orchidaceae) Species.
AB  - While it is generally acknowledged that orchid species rely on mycorrhizal fungi
      for completion of their life cycle, little is yet known about how mycorrhizal
      fungal diversity and community composition vary within and between closely
      related orchid taxa. In this study, we used 454 amplicon pyrosequencing to
      investigate variation in mycorrhizal communities between pure (allopatric) and
      mixed (sympatric) populations of two closely related Platanthera species
      (Platanthera bifolia and P. chlorantha) and putative hybrids. Consistent with
      previous research, the two species primarily associated primarily with members of
      the Ceratobasidiaceae and, to a lesser extent, with members of the Sebacinales
      and Tulasnellaceae. In addition, a large number of ectomycorrhizal fungi
      belonging to various families were observed. Although a considerable number of
      mycorrhizal fungi were common to both species, the fungal communities were
      significantly different between the two species. Individuals with intermediate
      morphology showed communities similar to P. bifolia, confirming previous results
      based on the genetic architecture and fragrance composition that putative hybrids
      essentially belonged to one of the parental species (P. bifolia). Differences in
      mycorrhizal communities between species were smaller in mixed populations than
      between pure populations, suggesting that variation in mycorrhizal communities
      was largely controlled by local environmental conditions. The small differences
      in mycorrhizal communities in mixed populations suggests that mycorrhizal fungi
      are most likely not directly involved in maintaining species boundaries between
      the two Platanthera species. However, seed germination experiments are needed to
      unambiguously assess the contribution of mycorrhizal divergence to reproductive
      isolation.

PMID- 27695107
TI  - Climate Change Influences on the Global Potential Distribution of the Mosquito
      Culex quinquefasciatus, Vector of West Nile Virus and Lymphatic Filariasis.
AB  - Rapid emergence of most vector-borne diseases (VBDs) may be associated with range
      expansion of vector populations. Culex quinquefasciatus Say 1823 is a potential
      vector of West Nile virus, Saint Louis encephalitis virus, and lymphatic
      filariasis. We estimated the potential distribution of Cx. quinquefasciatus under
      both current and future climate conditions. The present potential distribution of
      Cx. quinquefasciatus showed high suitability across low-latitude parts of the
      world, reflecting the current distribution of the species. Suitable conditions
      were identified also in narrow zones of North Africa and Western Europe. Model
      transfers to future conditions showed a potential distribution similar to that
      under present-day conditions, although with higher suitability in southern
      Australia. Highest stability with changing climate was between 30 degrees S and
      30 degrees N. The areas present high agreement among diverse climate models as
      regards distributional potential in the future, but differed in anticipating
      potential for distribution in North and Central Africa, southern Asia, central
      USA, and southeastern Europe. Highest disparity in model predictions across
      representative concentration pathways (RCPs) was in Saudi Arabia and Europe. The
      model predictions allow anticipation of changing distributional potential of the
      species in coming decades.

PMID- 27695109
TI  - Blood Component Therapy and Coagulopathy in Trauma: A Systematic Review of the
      Literature from the Trauma Update Group.
AB  - BACKGROUND: Traumatic coagulopathy is thought to increase mortality and its
      treatment to reduce preventable deaths. However, there is still uncertainty in
      this field, and available literature results may have been overestimated.
      METHODS: We searched the MEDLINE database using the PubMed platform. We
      formulated four queries investigating the prognostic weight of traumatic
      coagulopathy defined according to conventional laboratory testing, and the
      effectiveness in reducing mortality of three different treatments aimed at
      contrasting coagulopathy (high fresh frozen plasma/packed red blood cells ratios,
      fibrinogen, and tranexamic acid administration). Randomized controlled trials
      were selected along with observational studies that used a multivariable approach
      to adjust for confounding. Strict criteria were adopted for quality assessment
      based on a two-step approach. First, we rated quality of evidence according to
      the Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      criteria. Then, this rating was downgraded if other three criteria were not met:
      high reporting quality according to shared standards, absence of internal
      methodological and statistical issues not detailed by the GRADE system, and
      absence of external validity issues. RESULTS: With few exceptions, the GRADE
      rating, reporting and methodological quality of observational studies was "very
      low", with frequent external validity issues. The only two randomized trials
      retrieved were, instead, of high quality. Only weak evidence was found for a
      relation between coagulopathy and mortality. Very weak evidence was found
      supporting the use of fibrinogen administration to reduce mortality in trauma. On
      the other hand, we found high evidence that the use of 1:1 vs. 1:2 high fresh
      frozen plasma/packed red blood cells ratios failed to obtain a 12% mortality
      reduction. This does not exclude lower mortality rates, which have not been
      investigated. The use of tranexamic acid in trauma was supported by "high"
      quality evidence according to the GRADE classification but was downgraded to
      "moderate" for external validity issues. CONCLUSIONS: Tranexamic acid is
      effective in reducing mortality in trauma. The other transfusion practices we
      investigated have been inadequately studied in the literature, as well as the
      independent association between mortality and coagulopathy measured with
      traditional laboratory testing. Overall, in this field of research literature
      quality is poor.

PMID- 27695110
TI  - Gender-Disparities in Adults with Type 1 Diabetes: More Than a Quality of Care
      Issue. A Cross-Sectional Observational Study from the AMD Annals Initiative.
AB  - We evaluated gender-differences in quality of type 1 diabetes (T1DM) care.
      Starting from electronic medical records of 300 centers, 5 process indicators, 3
      favorable and 6 unfavorable intermediate outcomes, 6 treatment
      intensity/appropriateness measures and an overall quality score were measured.
      The likelihood of women vs. men (reference class) to be monitored, to reach
      outcomes, or to be treated has been investigated through multilevel logistic
      regression analyses; results are expressed as Odd Ratios (ORs) and 95% confidence
      intervals (95%CIs). The inter-center variability in the achievement of the
      unfavorable outcomes was also investigated. Overall, 28,802 subjects were
      analyzed (45.5% women). Women and men had similar age (44.5+/-16.0 vs. 45.0+/
      17.0 years) and diabetes duration (18.3+/-13.0 vs. 18.8+/-13.0 years). No between
      gender differences were found in process indicators. As for intermediate
      outcomes, women showed 33% higher likelihood of having HbA1c >=8.0% (OR = 1.33;
      95%CI: 1.25-1.43), 29% lower risk of blood pressure >=140/90 mmHg (OR = 0.71;
      95%CI: 0.65-0.77) and 27% lower risk of micro/macroalbuminuria (OR = 0.73; 95%CI:
      0.65-0.81) than men, while BMI, LDL-c and GFR did not significantly differ;
      treatment intensity/appropriateness was not systematically different between
      genders; overall quality score was similar in men and women. Consistently across
      centers a larger proportion of women than men had HbA1c >=8.0%, while a smaller
      proportion had BP >=140/90 mmHg. No gender-disparities were found in process
      measures and improvements are required in both genders. The systematic worse
      metabolic control in women and worse blood pressure in men suggest that
      pathophysiologic differences rather than the care provided might explain these
      differences.

PMID- 27695112
TI  - Efficient Percutaneous Delivery of the Antimelanogenic Agent Glabridin Using
      Cationic Amphiphilic Chitosan Micelles.
AB  - Partially myristoylated chitosan pyrrolidone carboxylate (PMCP) is a cationic
      amphiphilic chitosan derivative. Glabridin (Glab) from licorice root extracts is
      a hydrophobic antimelanogenic agent. Here we assessed the effects of cationic
      Glab-containing polymeric micelles derived from PMCP (Glab/PMCP-PM) on the
      ability of Glab to penetrate the skin and inhibit melanogenesis using a human
      skin model. The amount of Glab absorbed 24 h after the application of Glab/PMCP
      PM was approximately four times higher than that of conventional oil-in-water
      micelles (control) prepared using Tween 60. Further, the release of IL-1alpha, a
      mediator of inflammation, was not detected. Treatment with Glab/PMCP-PM
      significantly increased the inhibition of melanogenesis compared with control.
      The inhibition of melanogenesis depends upon the enhanced ability of Glab to
      penetrate the skin, particularly the epidermis. Moreover, the inhibition of
      melanogenesis and the cationic potential of the Glab/PMCP-PM levels were
      increased by the cationic phospholipid copolymer. Therefore, Glab/PMCP-PM shows
      potential as an effective transdermal delivery system for treating skin
      hyperpigmentation.

PMID- 27695111
TI  - Constitutive Association of Tie1 and Tie2 with Endothelial Integrins is
      Functionally Modulated by Angiopoietin-1 and Fibronectin.
AB  - Functional cross-talk between Tie2 and Integrin signaling pathways is essential
      to coordinate endothelial cell adhesion and migration in response to the
      extracellular matrix, yet the mechanisms behind this phenomenon are unclear.
      Here, we examine the possibility that receptor cross-talk is driven through
      uncharacterized Tie-integrin interactions on the endothelial surface. Using a
      live cell FRET-based proximity assay, we monitor Tie-integrin receptor
      recognition and demonstrate that both Tie1 and Tie2 readily associate with
      integrins alpha5beta1 and alphaVbeta3 through their respective ectodomains.
      Although not required, Tie2-integrin association is significantly enhanced in the
      presence of the extracellular component and integrin ligand fibronectin. In vitro
      binding assays with purified components reveal that Tie-integrin recognition is
      direct, and further demonstrate that the receptor binding domain of the Tie2
      ligand Ang-1, but not the receptor binding domain of Ang-2, can independently
      associate with alpha5beta1 or alphaVbeta3. Finally, we reveal that cooperative
      Tie/integrin interactions selectively stimulate ERK/MAPK signaling in the
      presence of both Ang-1 and fibronectin, suggesting a molecular mechanism to
      sensitize Tie2 to extracellular matrix. We provide a mechanistic model
      highlighting the role of receptor localization and association in regulating
      distinct signaling cascades and in turn, the angiogenic switch.

PMID- 27695114
TI  - A Pipelined Non-Deterministic Finite Automaton-Based String Matching Scheme Using
      Merged State Transitions in an FPGA.
AB  - This paper proposes a pipelined non-deterministic finite automaton (NFA)-based
      string matching scheme using field programmable gate array (FPGA) implementation.
      The characteristics of the NFA such as shared common prefixes and no failure
      transitions are considered in the proposed scheme. In the implementation of the
      automaton-based string matching using an FPGA, each state transition is
      implemented with a look-up table (LUT) for the combinational logic circuit
      between registers. In addition, multiple state transitions between stages can be
      performed in a pipelined fashion. In this paper, it is proposed that multiple one
      to-one state transitions, called merged state transitions, can be performed with
      an LUT. By cutting down the number of used LUTs for implementing state
      transitions, the hardware overhead of combinational logic circuits is greatly
      reduced in the proposed pipelined NFA-based string matching scheme.

PMID- 27695113
TI  - Increased Interstitial Concentrations of Glutamate and Pyruvate in Vastus
      Lateralis of Women with Fibromyalgia Syndrome Are Normalized after an Exercise
      Intervention - A Case-Control Study.
AB  - BACKGROUND: Fibromyalgia syndrome (FMS) is associated with central alterations,
      but controversies exist regarding the presence and role of peripheral factors.
      Microdialysis (MD) can be used in vivo to study muscle alterations in FMS.
      Furthermore for chronic pain conditions such as FMS, the mechanisms for the
      positive effects of exercise are unclear. This study investigates the
      interstitial concentrations of algesics and metabolites in the vastus lateralis
      muscle of 29 women with FMS and 28 healthy women before and after an exercise
      intervention. METHODS: All the participants went through a clinical examination
      and completed a questionnaire. In addition, their pressure pain thresholds (PPTs)
      in their upper and lower extremities were determined. For both groups, MD was
      conducted in the vastus lateralis muscle before and after a 15-week exercise
      intervention of mainly resistance training of the lower limbs. Muscle blood flow
      and interstitial muscle concentrations of lactate, pyruvate, glutamate, glucose,
      and glycerol were determined. RESULTS: FMS was associated with significantly
      increased interstitial concentrations of glutamate, pyruvate, and lactate. After
      the exercise intervention, the FMS group exhibited significant decreases in pain
      intensity and in mean interstitial concentrations of glutamate, pyruvate, and
      glucose. The decrease in pain intensity in FMS correlated significantly with the
      decreases in pyruvate and glucose. In addition, the FMS group increased their
      strength and endurance. CONCLUSION: This study supports the suggestion that
      peripheral metabolic and algesic muscle alterations are present in FMS patients
      and that these alterations contribute to pain. After an exercise intervention,
      alterations normalized, pain intensity decreased (but not abolished), and
      strength and endurance improved, all findings that suggest the effects of
      exercise are partially peripheral.

PMID- 27695116
TI  - Characterization and Expression Analysis of Phytoene Synthase from Bread Wheat
      (Triticum aestivum L.).
AB  - Phytoene synthase (PSY) regulates the first committed step of the carotenoid
      biosynthetic pathway in plants. The present work reports identification and
      characterization of the three PSY genes (TaPSY1, TaPSY2 and TaPSY3) in wheat
      (Triticum aestivum L.). The TaPSY1, TaPSY2, and TaPSY3 genes consisted of three
      homoeologs on the long arm of group 7 chromosome (7L), short arm of group 5
      chromosome (5S), and long arm of group 5 chromosome (5L), respectively in each
      subgenomes (A, B, and D) with a similarity range from 89% to 97%. The protein
      sequence analysis demonstrated that TaPSY1 and TaPSY3 retain most of conserved
      motifs for enzyme activity. Phylogenetic analysis of all TaPSY revealed an
      evolutionary relationship among PSY proteins of various monocot species. TaPSY
      derived from A and D subgenomes shared proximity to the PSY of Triticum urartu
      and Aegilops tauschii, respectively. The differential expression of TaPSY1,
      TaPSY2, and TaPSY3 in the various tissues, seed development stages, and stress
      treatments suggested their role in plant development, and stress condition.
      TaPSY3 showed higher expression in all tissues, followed by TaPSY1. The presence
      of multiple stress responsive cis-regulatory elements in promoter region of
      TaPSY3 correlated with the higher expression during drought and heat stresses has
      suggested their role in these conditions. The expression pattern of TaPSY3 was
      correlated with the accumulation of beta-carotene in the seed developmental
      stages. Bacterial complementation assay has validated the functional activity of
      each TaPSY protein. Hence, TaPSY can be explored in developing genetically
      improved wheat crop.

PMID- 27695115
TI  - Comparison of the Ability of Different Clinical Treatment Scores to Estimate
      Prognosis in High-Risk Early Breast Cancer Patients: A Hellenic Cooperative
      Oncology Group Study.
AB  - BACKGROUND-AIM: Early breast cancer is a heterogeneous disease, and, therefore,
      prognostic tools have been developed to evaluate the risk for distant recurrence.
      In the present study, we sought to develop a risk for recurrence score (RRS)
      based on mRNA expression of three proliferation markers in high-risk early breast
      cancer patients and evaluate its ability to predict risk for relapse and death.
      In addition the Adjuvant! Online score (AOS) was also determined for each
      patient, providing a 10-year estimate of relapse and mortality risk. We then
      evaluated whether RRS or AOS might possibly improve the prognostic information of
      the clinical treatment score (CTS), a model derived from clinicopathological
      variables. METHODS: A total of 1,681 patients, enrolled in two prospective phase
      III trials, were treated with anthracycline-based adjuvant chemotherapy.
      Sufficient RNA was extracted from 875 samples followed by multiplex quantitative
      reverse transcription-polymerase chain reaction for assessing RACGAP1, TOP2A and
      Ki67 mRNA expression. The CTS, slightly modified to fit our cohort, integrated
      the prognostic information from age, nodal status, tumor size, histological grade
      and treatment. Patients were also classified to breast cancer subtypes defined by
      immunohistochemistry. Likelihood ratio (LR) tests and concordance indices were
      used to estimate the relative increase in the amount of information provided when
      either RRS or AOS is added to CTS. RESULTS: The optimal RRS, in terms of disease
      free survival (DFS) and overall survival (OS), was based on the co-expression of
      two of the three evaluated genes (RACGAP1 and TOP2A). CTS was prognostic for DFS
      (p<0.001), while CTS, AOS and RRS were all prognostic for OS (p<0.001, p<0.001
      and p = 0.036, respectively). The use of AOS in addition to CTS added prognostic
      information regarding DFS (LR-Deltachi2 8.7, p = 0.003), however the use of RRS
      in addition to CTS did not. For estimating OS, the use of either AOS or RRS in
      addition to CTS added significant prognostic information. Specifically, the use
      of both CTS and AOS had significantly better prognostic value vs. CTS alone (LR
      Deltachi2 20.8, p<0.001), as well as the use of CTS and RRS vs. CTS alone (LR
      Deltachi2 4.8, p = 0.028). Additionally, more patients were scored as high-risk
      by AOS than CTS. According to immunohistochemical subtypes, prognosis was
      improved in the Luminal A (LR-Deltachi2 7.2, p = 0.007) and Luminal B (LR
      Deltachi2 8.3, p = 0.004) subtypes, in HER2-negative patients (LR-Deltachi2 23.4,
      p<0.001) and in patients with >3 positive nodes (LR-Deltachi2 23.9, p<0.001) when
      AOS was added to CTS. CONCLUSIONS: The current study has shown a clear benefit in
      predicting overall survival of high-risk early breast cancer patients when
      combining CTS with either AOS or RRS. The combination of CTS and AOS adds
      significant prognostic information compared to CTS alone for DFS, while the
      combination of CTS with either AOS or RRS has better prognostic value than CTS
      alone for OS. These findings could possibly add on the information needed for the
      best risk prediction strategy in high-risk early breast cancer patients in a
      rather simple and inexpensive way, especially in Luminal A and B subtypes, HER2
      negative patients and those with >3 positive nodes.

PMID- 27695117
TI  - Observation of Influence of Cataract Surgery on the Ocular Surface.
AB  - INTRODUCTION: To evaluate meibomian gland function, changes of lacrimal tears and
      ocular surface parameters and tear inflammatory mediators following cataract
      surgery. METHODS: 48 eyes of 34 patients who underwent uncomplicated
      phacoemulsification were involved and divided into 2 groups with those who had
      preexisting dry-eye before cataract surgery and those who did not. Ocular symptom
      score, Schirmer I test, tear film break-up time (TBUT), corneal sensitivity
      threshold, corneal staining, inflammatory cytokine activities, lid margin
      abnormalities, meibum expressibility, meibum quality and meibomian gland imaging
      were evaluated preoperatively, at 1 day, 1 and 2 months postoperatively. RESULTS:
      Ocular symptom scores were worse at 1 and 2 months postoperatively but, TBUT,
      corneal staining score and corneal sensitivity threshold showed gradual
      improvements at 1 month and 2 months postoperatively (p<0.05, respectively).
      Interestingly there were statistically significant improvements in TBUT, corneal
      staining score and corneal sensitivity threshold at 1 month postoperatively when
      topical eye drops were used compared to the period without topical therapy which
      is the months 2 postoperatively. There were statistically significant decreases
      in IL-1beta, IL-6, IL-8, MCP-1, TNF-alpha and IFN-gamma concentrations at 1 and 2
      months postoperatively. Lid margin abnormalities, meibum quality and
      expressibility scores increased significantly (p < 0.05, respectively) at
      postoperative period. Compared with the no dry eye group, dry eye group revealed
      significantly higher ocular symptom scores, lower TBUT, higher lid margin
      abnormalities, meibum quality and expressibility scores after cataract surgery.
      There were significant correlations between IL-6 and parameters of dry eye, and
      between MGD parameters and ocular symptom scores. CONCLUSIONS: Our study revealed
      that meibomian gland function is influenced after cataract surgery accompanying
      structural changes and these were correlated with increased ocular symptom
      scores. Therefore, it could elucidate the development of dry eye related to
      cataract surgery.

PMID- 27695118
TI  - High Coverage and Utilization of Fortified Take-Home Rations among Children 6-35
      Months of Age Provided through the Integrated Child Development Services Program:
      Findings from a Cross-Sectional Survey in Telangana, India.
AB  - The Integrated Child Development Services (ICDS) in the State of Telangana,
      India, freely provides a fortified complementary food product, Bal Amrutham, as a
      take-home ration to children 6-35 months of age. In order to understand the
      potential for impact of any intervention, it is essential to assess coverage and
      utilization of the program and to address the barriers to its coverage and
      utilization. A two-stage, stratified cross-sectional cluster survey was conducted
      to estimate the coverage and utilization of Bal Amrutham and to identify their
      barriers and drivers. In randomly selected catchment areas of ICDS centers,
      children under 36 months of age were randomly selected. A questionnaire,
      constructed from different validated and standard modules and designed to collect
      coverage data on nutrition programs, was administered to caregivers. A total of
      1,077 children were enrolled in the survey. The coverage of the fortified take
      home ration was found to be high among the target population. Nearly all
      caregivers (93.7%) had heard of Bal Amrutham and 86.8% had already received the
      product for the target child. Among the children surveyed, 57.2% consumed the
      product regularly. The ICDS program's services were not found to be a barrier to
      product coverage. In fact, the ICDS program was found to be widely available,
      accessible, accepted, and utilized by the population in both urban and rural
      catchment areas, as well as among poor and non-poor households. However, two
      barriers to optimal coverage were found: the irregular supply of the product to
      the beneficiaries and the intra-household sharing of the product. Although
      sharing was common, the product was estimated to provide the target children with
      significant proportions of the daily requirements of macro- and micronutrients.
      Bal Amrutham is widely available, accepted, and consumed among the target
      population in the catchment areas of ICDS centers. The coverage of the product
      could be further increased by improving the supply chain.

PMID- 27695119
TI  - The Acute Effects of Interval-Type Exercise on Glycemic Control in Type 2
      Diabetes Subjects: Importance of Interval Length. A Controlled, Counterbalanced,
      Crossover Study.
AB  - : Interval-type exercise is effective for improving glycemic control, but the
      optimal approach is unknown. The purpose of this study was to determine the
      importance of the interval length on changes in postprandial glycemic control
      following a single exercise bout. Twelve subjects with type 2 diabetes completed
      a cross-over study with three 1-hour interventions performed in a non-randomized
      but counter-balanced order: 1) Interval walking consisting of repeated cycles of
      3 min slow (aiming for 54% of Peak oxygen consumption rate [VO2peak]) and 3 min
      fast (aiming for 89% of VO2peak) walking (IW3); 2) Interval walking consisting of
      repeated cycles of 1 min slow and 1 min fast walking (IW1) and 3) No walking
      (CON). The exercise interventions were matched with regards to walking speed, and
      VO2 and heart rate was assessed throughout all interventions. A 4-hour liquid
      mixed meal tolerance test commenced 30 min after each intervention, with blood
      samples taken regularly. IW3 and IW1 resulted in comparable mean VO2 and heart
      rates. Overall mean postprandial blood glucose levels were lower after IW3
      compared to CON (10.3+/-3.0 vs. 11.1+/-3.3 mmol/L; P < 0.05), with no significant
      differences between IW1 (10.5+/-2.8 mmol/L) and CON or IW3 and IW1 (P > 0.05 for
      both). Conversely blood glucose levels at specific time points during the MMTT
      differed significantly following both IW3 and IW1 as compared to CON. Our
      findings support the previously found blood glucose lowering effect of IW3 and
      suggest that reducing the interval length, while keeping the walking speed and
      time spend on fast and slow walking constant, does not result in additional
      improvements. TRIAL REGISTRATION: ClinicalTrials.gov NCT02257190.

PMID- 27695120
TI  - An Exploration of Human Well-Being Bundles as Identifiers of Ecosystem Service
      Use Patterns.
AB  - We take a social-ecological systems perspective to investigate the linkages
      between ecosystem services and human well-being in South Africa. A recent paper
      identified different types of social-ecological systems in the country, based on
      distinct bundles of ecosystem service use. These system types were found to
      represent increasingly weak direct feedbacks between nature and people, from
      rural "green-loop" communities to urban "red-loop" societies. Here we construct
      human well-being bundles and explore whether the well-being bundles can be used
      to identify the same social-ecological system types that were identified using
      bundles of ecosystem service use. Based on national census data, we found three
      distinct well-being bundle types that are mainly characterized by differences in
      income, unemployment and property ownership. The distribution of these well-being
      bundles approximates the distribution of ecosystem service use bundles to a
      substantial degree: High levels of income and education generally coincided with
      areas characterised by low levels of direct ecosystem service use (or red-loop
      systems), while the majority of low well-being areas coincided with medium and
      high levels of direct ecosystem service use (or transition and green-loop
      systems). However, our results indicate that transformations from green-loop to
      red-loop systems do not always entail an immediate improvement in well-being,
      which we suggest may be due to a time lag between changes in the different system
      components. Using human well-being bundles as an indicator of social-ecological
      dynamics may be useful in other contexts since it is based on socio-economic data
      commonly collected by governments, and provides important insights into the
      connections between ecosystem services and human well-being at policy-relevant
      sub-national scales.

PMID- 27695121
TI  - The Potential of Class II Bacteriocins to Modify Gut Microbiota to Improve Host
      Health.
AB  - Production of bacteriocins is a potential probiotic feature of many lactic acid
      bacteria (LAB) as it can help prevent the growth of pathogens in gut
      environments. However, knowledge on bacteriocin producers in situ and their
      function in the gut of healthy animals is still limited. In this study, we
      investigated five bacteriocin-producing strains of LAB and their isogenic non
      producing mutants for probiotic values. The LAB bacteriocins, sakacin A (SakA),
      pediocin PA-1 (PedPA-1), enterocins P, Q and L50 (enterocins), plantaricins EF
      and JK (plantaricins) and garvicin ML (GarML), are all class II bacteriocins, but
      they differ greatly from each other in terms of inhibition spectrum and
      physicochemical properties. The strains were supplemented to mice through
      drinking water and changes on the gut microbiota composition were interpreted
      using 16S rRNA gene analysis. In general, we observed that overall structure of
      the gut microbiota remained largely unaffected by the treatments. However, at
      lower taxonomic levels, some transient but advantageous changes were observed.
      Some potentially problematic bacteria were inhibited (e.g., Staphylococcus by
      enterocins, Enterococcaceae by GarML, and Clostridium by plantaricins) and the
      proportion of LAB was increased in the presence of SakA-, plantaricins- and GarML
      producing bacteria. Moreover, the treatment with GarML-producing bacteria co
      occurred with decreased triglyceride levels in the host mice. Taken together, our
      results indicate that several of these bacteriocin producers have potential
      probiotic properties at diverse levels as they promote favorable changes in the
      host without major disturbance in gut microbiota, which is important for normal
      gut functioning.

PMID- 27695122
TI  - Involvement of Macrophages in the Pathogenesis of Familial Amyloid Polyneuropathy
      and Efficacy of Human iPS Cell-Derived Macrophages in Its Treatment.
AB  - We hypothesized that tissue-resident macrophages in familial amyloid
      polyneuropathy (FAP) patients will exhibit qualitative or quantitative
      abnormalities, that may accelerate transthyretin (TTR)-derived amyloid
      deposition. To evaluate this, we examined the number and subset of tissue
      resident macrophages in heart tissue from amyloid-deposited FAP and control
      patients. In both FAP and control patients, tissue-resident macrophages in heart
      tissue were all Iba+/CD163+/CD206+ macrophages. However, the number of
      macrophages was significantly decreased in FAP patients compared with control
      patients. Furthermore, the proportion of intracellular TTR in CD14+ monocytes was
      reduced in peripheral blood compared with healthy donors. Based on these results,
      we next examined degradation and endocytosis of TTR in human induced pluripotent
      stem (iPS) cell-derived myeloid lineage cells (MLs), which function like
      macrophages. iPS-MLs express CD163 and CD206, and belong to the inhibitory
      macrophage category. In addition, iPS-MLs degrade both native and aggregated TTR
      in a cell-dependent manner in vitro. Further, iPS-MLs endocytose aggregated, and
      especially polymerized, TTR. These results suggest that decreased tissue
      localized macrophages disrupt clearance of TTR-derived amyloid deposits, leading
      to progression of a pathological condition in FAP patients. To improve this
      situation, clinical application of pluripotent stem cell-derived MLs may be
      useful as an approach for FAP therapy.

PMID- 27695123
TI  - Simultaneous Determination of Black Tea-Derived Catechins and Theaflavins in
      Tissues of Tea Consuming Animals Using Ultra-Performance Liquid-Chromatography
      Tandem Mass Spectrometry.
AB  - The bioavailability, tissue distribution and metabolic fate of the major tea
      polyphenols, catechins and theaflavins as well as their gallated derivatives are
      yet to be precisely elucidated on a single identification platform for assessment
      of their relative bioefficacy in vivo. This is primarily due to the lack of
      suitable analytical tools for their simultaneous determination especially in an
      in vivo setting, which continues to constrain the evaluation of their relative
      health beneficiary potential and therefore prospective therapeutic application.
      Herein, we report a rapid and sensitive Ultra-Performance Liquid Chromatography
      Tandem Mass Spectrometry (UPLC-MS/MS) based method for the simultaneous
      determination of the major catechins and theaflavins in black tea infusions as
      well as in different vital tissues and body fluids of tea-consuming guinea pigs.
      This method allowed efficient separation of all polyphenols within seven minutes
      of chromatographic run and had a lower limit of quantification (LLOQ) of ~5
      ng/ml. Using this method, almost all bioactive catechins and theaflavins could be
      simultaneously detected in the plasma of guinea pigs orally administered 5% black
      tea for 14 days. Our method could further detect the majority of these
      polyphenols in the lung and kidney as well as identify the major catechin
      metabolites in the urine of the tea-consuming animals. Overall, our study
      presents a novel tool for simultaneous detection and quantitation of both
      catechins and theaflavins in a single detection platform that could potentially
      enable precise elucidation of their relative bioavailability and bioefficacy as
      well as true health beneficiary potential in vivo. Such information would
      ultimately facilitate the accurate designing of therapeutic strategies utilizing
      high efficacy formulations of tea polyphenols for effective mitigation of
      oxidative damage and inflammation in humans as well as prevention of associated
      diseases.

PMID- 27695124
TI  - S100beta-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the
      Embryonic Pituitary Gland.
AB  - The anterior and intermediate lobes of the pituitary gland develop through
      invagination of the oral ectoderm and as they are endocrine tissues, they
      participate in the maintenance of vital functions via the synthesis and secretion
      of numerous hormones. We recently observed that several extrapituitary cells
      invade the anterior lobe of the developing pituitary gland. This raised the
      question of the origin(s) of these S100beta-positive cells, which are not classic
      endocrine cells but instead comprise a heterogeneous cell population with plural
      roles, especially as stem/progenitor cells. To better understand the roles of
      these S100beta-positive cells, we performed immunohistochemical analysis using
      several markers in S100beta/GFP-TG rats, which express GFP in S100beta-expressing
      cells under control of the S100beta promoter. GFP-positive cells were present as
      mesenchymal cells surrounding the developing pituitary gland and at Atwell's
      recess but were not present in the anterior lobe on embryonic day 15.5. These
      cells were negative for SOX2, a pituitary stem/progenitor marker, and PRRX1, a
      mesenchyme and pituitary stem/progenitor marker. However, three days later, GFP
      positive and PRRX1-positive (but SOX2-negative) cells were observed in the
      parenchyma of the anterior lobe. Furthermore, some GFP-positive cells were
      positive for vimentin, p75, isolectin B4, DESMIN, and Ki67. These data suggest
      that S100beta-positive cells of extrapituitary origin invade the anterior lobe,
      undergoing proliferation and diverse transformation during pituitary
      organogenesis.

PMID- 27695126
TI  - Simultaneous Maximum-Likelihood Reconstruction of Absorption Coefficient,
      Refractive Index and Dark-Field Scattering Coefficient in X-Ray Talbot-Lau
      Tomography.
AB  - A maximum-likelihood reconstruction technique for X-ray Talbot-Lau tomography is
      presented. This technique allows the iterative simultaneous reconstruction of
      discrete distributions of absorption coefficient, refractive index and a dark
      field scattering coefficient. This technique avoids prior phase retrieval in the
      tomographic projection images and thus in principle allows reconstruction from
      tomographic data with less than three phase steps per projection. A numerical
      phantom is defined which is used to evaluate convergence of the technique with
      regard to photon statistics and with regard to the number of projection angles
      and phase steps used. It is shown that the use of a random phase sampling pattern
      allows the reconstruction even for the extreme case of only one single phase step
      per projection. The technique is successfully applied to measured tomographic
      data of a mouse. In future, this reconstruction technique might also be used to
      implement enhanced imaging models for X-ray Talbot-Lau tomography. These
      enhancements might be suited to correct for example beam hardening and dispersion
      artifacts and improve overall image quality of X-ray Talbot-Lau tomography.

PMID- 27695125
TI  - Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides
      Designed as Phosphodiesterase-4 Inhibitors.
AB  - Prior investigations showed that increased levels of cyclic AMP down-regulate
      lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE)4
      as therapeutic target. Here, we described the synthesis, pharmacological profile
      and docking properties of a novel sulfonamide series (5 and 6a-k) designed as
      PDE4 inhibitors. Compounds were screened for their selectivity against the four
      isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect
      on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR)
      was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was
      employed as a behavioral correlate of emesis in rodents. As compared to rolipram,
      the most promising screened compound, 6a (LASSBio-448) presented a better
      inhibitory index concerning PDE4D/PDE4A or PDE4D/PDE4B. Accordingly, docking
      analyses of the putative interactions of LASSBio-448 revealed similar poses in
      the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and
      PDE4D. LASSBio-448 (100 mg/kg, oral), 1 h before provocation, inhibited allergen
      induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an
      interventional approach, LASSBio-448 reversed ongoing lung eosinophilic
      infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen
      provocation, in a mechanism clearly associated with blockade of pro-inflammatory
      mediators such as IL-4, IL-5, IL-13 and eotaxin-2. LASSBio-448 (2.5 and 10 mg/kg)
      also prevented inflammation and AHR induced by LPS. Finally, the sulfonamide
      derivative was shown to be less pro-emetic than rolipram and cilomilast in the
      assay employed. These findings suggest that LASSBio-448 is a new PDE4 inhibitor
      with marked potential to prevent and reverse pivotal pathological features of
      diseases characterized by lung inflammation, such as asthma.

PMID- 27695128
TI  - Correlation between Serum Lipid Levels and Measured Glomerular Filtration Rate in
      Chinese Patients with Chronic Kidney Disease.
AB  - INTRODUCTION: Dyslipidemia is often detected in patients with chronic kidney
      disease (CKD). Previous studies of the relationship between lipid profiles and
      kidney function have yielded variable results. We aimed to investigate the
      correlation between serum lipid levels and kidney function evaluated by measured
      glomerular filtration rate (mGFR) in Chinese patients with CKD. METHODS: A cross
      sectional study was conducted on 2036 Chinese CKD patients who had mGFR. Linear
      regression analysis was performed to evaluate the correlation between different
      serum lipid levels and mGFR, while logistic regression analysis was used to
      investigate the association between CKD stages and the risk of different types of
      dyslipidemia. RESULTS: The mean age was 55 years and the mean mGFR was 63
      mL/min/1.73m2. After adjusting for some confounders (age, gender, body mass
      index, a history of diabetes, fasting glucose, a history of hypertension,
      systolic blood pressure, diastolic blood pressure, smoking status, hemoglobin,
      serum potassium, serum albumin, and serum uric acid), serum triglyceride level
      showed a negative correlation with mGFR (beta = -0.006, P = 0.006) in linear
      regression analysis, and CKD stages were positively related to the risk of
      hypertriglyceridemia (odds ratios were 1.329, 1.868, 2.514 and P were 0.046, <
      0.001, < 0.001 for CKD stage 2, 3, 4/5, respectively) in logistic regression
      anlysis. CONCLUSIONS: Serum triglyceride level is independently association with
      mGFR. Patients with reduced kidney function are more likely to have higher serum
      triglyceride levels. Further longitudinal, multicenter and well-conducted studies
      are needed to provide more evidence.

PMID- 27695127
TI  - Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via
      Interferon Beta and Indoleamine-2,3-Dioxygenase.
AB  - Respiratory syncytial virus (RSV) has been reported to infect human mesenchymal
      stem cells (MSCs) but the consequences are poorly understood. MSCs are present in
      nearly every organ including the nasal mucosa and the lung and play a role in
      regulating immune responses and mediating tissue repair. We sought to determine
      whether RSV infection of MSCs enhances their immune regulatory functions and
      contributes to RSV-associated lung disease. RSV was shown to replicate in human
      MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts.
      RSV-infected MSCs showed differentially altered expression of cytokines and
      chemokines such as IL-1beta, IL6, IL-8 and SDF-1 compared to epithelial cells.
      Notably, RSV-infected MSCs exhibited significantly increased expression of IFN
      beta (~100-fold) and indoleamine-2,3-dioxygenase (IDO) (~70-fold) than in mock
      infected MSCs. IDO was identified in cytosolic protein of infected cells by
      Western blots and enzymatic activity was detected by tryptophan catabolism assay.
      Treatment of PBMCs with culture supernatants from RSV-infected MSCs reduced their
      proliferation in a dose dependent manner. This effect on PBMC activation was
      reversed by treatment of MSCs with the IDO inhibitors 1-methyltryptophan and
      vitamin K3 during RSV infection, a result we confirmed by CRISPR/Cas9-mediated
      knockout of IDO in MSCs. Neutralizing IFN-beta prevented IDO expression and
      activity. Treatment of MSCs with an endosomal TLR inhibitor, as well as a
      specific inhibitor of the TLR3/dsRNA complex, prevented IFN-beta and IDO
      expression. Together, these results suggest that RSV infection of MSCs alters
      their immune regulatory function by upregulating IFN-beta and IDO, affecting
      immune cell proliferation, which may account for the lack of protective RSV
      immunity and for chronicity of RSV-associated lung diseases such as asthma and
      COPD.

PMID- 27695129
TI  - Revisiting the Phylogeny of the Animal Formins: Two New Subtypes, Relationships
      with Multiple Wing Hairs Proteins, and a Lost Human Formin.
AB  - Formins are a widespread family of eukaryotic cytoskeleton-organizing proteins.
      Many species encode multiple formin isoforms, and for animals, much of this
      reflects the presence of multiple conserved subtypes. Earlier phylogenetic
      analyses identified seven major formin subtypes in animals (DAAM, DIAPH, FHOD,
      FMN, FMNL, INF, and GRID2IP/delphilin), but left a handful of formins,
      particularly from nematodes, unassigned. In this new analysis drawing from
      genomic data from a wider range of taxa, nine formin subtypes are identified that
      encompass all the animal formins analyzed here. Included in this analysis are
      Multiple Wing Hairs proteins (MWH), which bear homology to formin N-terminal
      domains. Originally identified in Drosophila melanogaster and other arthropods,
      MWH-related proteins are also identified here in some nematodes (including
      Caenorhabditis elegans), and are shown to be related to a novel MWH-related
      formin (MWHF) subtype. One surprising result of this work is the discovery that a
      family of pleckstrin homology domain-containing formins (PHCFs) is represented in
      many vertebrates, but is strikingly absent from placental mammals. Consistent
      with a relatively recent loss of this formin, the human genome retains fragments
      of a defunct homologous formin gene.

PMID- 27695130
TI  - Cost-Effectiveness Analysis of Test-Based versus Presumptive Treatment of
      Uncomplicated Malaria in Children under Five Years in an Area of High
      Transmission in Central Ghana.
AB  - BACKGROUND: The presumptive approach of confirming malaria in health facilities
      leads to over-diagnosis of malaria, over use of anti-malaria drugs and the risk
      of drug resistance development. WHO recommends parasitological confirmation
      before treatment with artemisinin-based combination therapy (ACT) in all
      suspected malaria patients. The use of malaria rapid diagnostic tests (mRDTs)
      would make it possible for prescribers to diagnose malaria at point-of-care and
      better target the use of antimalarials. Therefore, a cost-effectiveness analysis
      was performed on the introduction of mRDTs for management of malaria in under
      five children in a high transmission area in Ghana where presumptive diagnosis
      was the norm in public health centres. METHODS: A cluster-randomised controlled
      trial where thirty-two health centres were randomised into test-based diagnosis
      of malaria using mRDTs (intervention) or clinical judgement (control) was used to
      measure the effect of mRDTs on appropriate treatment: 'a child with a positive
      reference diagnosis prescribed a course of ACT or a child with a negative
      reference diagnosis not given an ACT'. Cost data was collected from five
      purposively selected health centres and used to estimate the health sector costs
      of performing an mRDT and treat children for malaria and other common febrile
      illnesses. Costs of training healthcare personnel and supervision in the study
      period were also collected. A sample of caregivers to children participating in
      the trial was interviewed about household cost incurred on transport, drugs,
      fees, and special food during a period of one week after the health centre visit
      as well as days unable to work. A decision model approach was used to calculate
      the incremental cost-effectiveness ratios (ICERs). Univariate and multivariate
      sensitivity analyses were applied to assess the robustness of ICERs. RESULTS: The
      availability of mRDTs for malaria diagnosis resulted in fewer ACT treatments
      compared to the clinical judgement approach (73% versus 81%) and more children
      appropriately treated (70% versus 57%). The introduction of mRDT-based diagnosis
      would cost the Ministry of Health US$18.6 per extra appropriately treated child
      under five compared to clinical judgement while the ICER from a societal
      perspective was lower at US$11.0 per appropriately treated child. ICERs were
      sensitive to a decrease in adherence to negative mRDTs, malaria positivity rate
      and specificity of the mRDT. CONCLUSION: The introduction of mRDTs is likely to
      be considered cost-effective in this high transmission setting as this
      intervention increased the number of appropriately treated children at low cost.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00832754.

PMID- 27695131
TI  - Periodic zone-MPC with asymmetric costs for outpatient-ready safety of an
      artificial pancreas to treat type 1 diabetes.
AB  - A novel Model Predictive Control (MPC) law for an Artificial Pancreas (AP) to
      automatically deliver insulin to people with type 1 diabetes is proposed. The MPC
      law is an enhancement of the authors' zone-MPC approach that has successfully
      been trialled in-clinic, and targets the safe outpatient deployment of an AP. The
      MPC law controls blood-glucose levels to a diurnally time-dependent zone, and
      enforces diurnal, hard input constraints. The main algorithmic novelty is the use
      of asymmetric input costs in the MPC problem's objective function. This improves
      safety by facilitating the independent design of the controller's responses to
      hyperglycemia and hypoglycemia. The proposed controller performs predictive pump
      suspension in the face of impending hypoglycemia, and subsequent predictive pump
      resumption, based only on clinical needs and feedback. The proposed MPC
      strategy's benefits are demonstrated by in-silico studies as well as highlights
      from a US Food and Drug Administration approved clinical trial in which 32
      subjects each completed two 25 hour closed-loop sessions employing the proposed
      MPC law.

PMID- 27695132
TI  - Rough Gold Electrodes for Decreasing Impedance at the Electrolyte/Electrode
      Interface.
AB  - Electrode polarization at the electrolyte/electrode interface is often
      undesirable for bio-sensing applications, where charge accumulated over an
      electrode at constant potential causes large potential drop at the interface and
      low measurement sensitivity. In this study, novel rough electrodes were developed
      for decreasing electrical impedance at the interface. The electrodes were
      fabricated using electrochemical deposition of gold and sintering of gold
      nanoparticles. The performances of the gold electrodes were compared with
      platinum black electrodes. A constant phase element model was used to describe
      the interfacial impedance. Hundred folds of decrease in interfacial impedance
      were observed for fractal gold electrodes and platinum black. Biotoxicity,
      contact angle, and surface morphology of the electrodes were investigated.
      Relatively low toxicity and hydrophilic nature of the fractal and granulated gold
      electrodes make them suitable for bioimpedance and cell electromanipulation
      studies compared to platinum black electrodes which are both hydrophobic and
      toxic.

PMID- 27695133
TI  - Bromomethane Contamination in the Cathode of Proton Exchange Membrane Fuel Cells.
AB  - The effects of bromomethane (BrCH3), an airborne contaminant, on the performance
      of a single PEMFC are compared with that of another halocarbon, chlorobenzene.
      Under a constant current of 1 A cm-2 and at 45  degrees C, 20 ppm bromomethane
      causes approximately 30% cell voltage loss in approximately 30 h, as opposed to
      much more rapid performance degradation observed with chlorobenzene.
      Electrochemical impedance spectroscopy, cyclic voltammetry, linear scanning
      voltammetry, and polarization measurements are applied to characterize the
      temporary electrochemical reaction effect and permanent performance effects. X
      ray absorption spectroscopy is used to confirm that Br is adsorbed on the Pt
      electrocatalyst surface. We conclude that airborne bromomethane poisons a PEMFC
      in a different way from chlorobenzene because it is largely hydrolyzed to
      bromide, Br-, which is then excluded from the Pt catalyst by the negatively
      charged Nafion ionomer. The little Br- and bromomethane that adsorbs on the Pt
      surface can be partially removed by cycling but causes some irreversible surface
      area loss.

PMID- 27695135
TI  - A finite deformation model of planar serpentine interconnects for stretchable
      electronics.
AB  - Lithographically defined interconnects with filamentary, serpentine
      configurations have been widely used in various forms of stretchable electronic
      devices, owing to the ultra-high stretchability that can be achieved and the
      relative simple geometry that facilitates the design and fabrication. Theoretical
      models of serpentine interconnects developed previously for predicting the
      performance of stretchability were mainly based on the theory of infinitesimal
      deformation. This assumption, however, does not hold for the interconnects that
      undergo large levels of deformations before the structural failure. Here, an
      analytic model of serpentine interconnects is developed starting from the finite
      deformation theory of planar, curved beams. Finite element analyses (FEA) of the
      serpentine interconnects with a wide range of geometric parameters were performed
      to validate the developed model. Comparisons of the predicted stretchability to
      the estimations of linear models provide quantitative insights into the effect of
      finite deformation. Both the theoretical and numerical results indicate that a
      considerable overestimation (e.g., > 50% relatively) of the stretchability can be
      induced by the linear model for many representative shapes of serpentine
      interconnects. Furthermore, a simplified analytic solution of the stretchability
      is obtained by using an approximate model to characterize the nonlinear effect.
      The developed models can be used to facilitate the designs of serpentine
      interconnects in future applications.

PMID- 27695136
TI  - Residential Instability, Family Support, and Parent-Child Relationships Among
      Ethnically Diverse Urban Families.
AB  - From a social disorganization standpoint, neighborhood residential instability
      potentially brings negative consequences to parent-child relationship qualities,
      but family social support and racial/ethnic identity may modify this association.
      Using data (n = 3,116) from the Project on Human Development in Chicago
      Neighborhoods, this study examines associations between neighborhood residential
      instability and parent-child warmth and conflict, whether family social support
      moderates associations between residential instability and parent-child
      relationships, and variation by race/ethnicity. Multilevel models reveal that
      residential instability undermines parent-child relationship qualities,
      particularly for non-White individuals. Family support is a protective factor for
      families in less stable neighborhoods, and specifically buffers the association
      between neighborhood residential instability and reduced parent-child warmth.
      Among Hispanics, family support mitigates the association between residential
      instability and heightened parent-child conflict. Findings highlight residential
      instability as a detriment to parent-child relationships; families in unstable
      neighborhoods may benefit from family social support.

PMID- 27695134
TI  - Biochemical and Biophysical Understanding of Metal Ion Selectivity of DNAzymes.
AB  - This review summarizes research into the metal-binding properties of catalytic
      DNAzymes, towards the goal of understanding the structural properties leading to
      metal ion specificity. Progress made and insight gained from a range of
      biochemical and biophysical techniques are covered, and promising directions for
      future investigations are discussed.

PMID- 27695138
TI  - Effects of Religiosity Dimensions on Physical Health across Non-elderly Black and
      White American Panels.
AB  - This investigation-based on a three-wave national panel of Black and White
      Americans aged 64 or younger at wave one-gauges variation across races in the
      indirect, moderating, and direct effects of public and subjective religiosity on
      a latent physical health outcome comprising chronic illnesses, subjective health,
      and functional limitations. The multi-population LISREL model specifically
      addresses the mechanisms through which religiosity is typically presumed to
      indirectly foster health: enhancement of social support and self-appraisals, and
      suppression of stress-exposure and unhealthy habits. The extent to which
      religiosity buffers or exacerbates the impact of specific stressors is also
      examined. The impact of religiosity on health appears to hinge on race and
      religiosity dimension: Public religiosity indirectly enhances Blacks' health
      slightly, and apparently buffers any negative impact of financial strain on their
      health. Public religiosity does not influence Whites' health; and subjective
      religiosity does not influence health in either race. The models control for
      multiple socio-demographic factors.

PMID- 27695137
TI  - Tension Amplification in Tethered Layers of Bottle-Brush Polymers.
AB  - Molecular dynamics simulations of a coarse-grained bead-spring model have been
      used to study the effects of molecular crowding on the accumulation of tension in
      the backbone of bottle-brush polymers tethered to a flat substrate. The number of
      bottle-brushes per unit surface area, Sigma, as well as the lengths of the bottle
      brush backbones Nbb (50 <= Nbb <= 200) and side chains Nsc (50 <= Nsc <= 200)
      were varied to determine how the dimensions and degree of crowding of bottle
      brushes give rise to bond tension amplification along the backbone, especially
      near the substrate. From these simulations, we have identified three separate
      regimes of tension. For low Sigma, the tension is due solely to intramolecular
      interactions and is dominated by the side chain repulsion that governs the
      lateral brush dimensions. With increasing Sigma, the interactions between bottle
      brush polymers induce compression of the side chains, transmitting increasing
      tension to the backbone. For large Sigma, intermolecular side chain repulsion
      increases, forcing side chain extension and reorientation in the direction normal
      to the surface and transmitting considerable tension to the backbone.

PMID- 27695139
TI  - An unexpected Lewis acid catalyzed Diels-Alder cycloaddition of aryl allenes and
      acrylates.
AB  - An unexpected [4+2] cycloaddition of aryl allenes and simple acrylate derivatives
      is reported. This process functions well with a variety of allenes and acrylates
      to generate bi- and tricyclic dihydronaphthalene derivatives through a
      nonconventional bond disconnection.

PMID- 27695141
TI  - 'They don't live in my house every day': How understanding lives can aid
      understandings of smoking.
AB  - While the prevalence of smoking in western countries has substantially reduced
      following the introduction of comprehensive tobacco control programs, reduction
      strategies such as the introduction of smokefree legislation, media campaigns and
      individual and group support for people trying to quit have been less successful
      with people living on low income, suggesting the need for new ways to engage with
      people who smoke. We argue that, rather than focusing solely on researching
      smoking behaviors to generate new understandings of why people smoke, people
      working in the broad area of public health should look more widely at peoples'
      lives in order to understand their smoking. Using a biographical, narrative
      perspective as part of a wider ethnographic study of 12 families living in one
      community within Liverpool in 2006, we argue that understandings that position
      smoking purely as a harmful, deviant behavior, fail to capture the cultural
      complexity of the lives of smokers and the changing place and meaning of
      cigarettes over a person's lifetime, and may explain why smokers fail to engage
      with smoking cessation services and continue to smoke.

PMID- 27695140
TI  - Cannabisol, a novel Delta9-THC dimer possessing a unique methylene bridge,
      isolated from Cannabis sativa.
AB  - Cannabisol (1), a unique dimer of Delta9-tetrahydrocannabinol (Delta9-THC) with a
      methylene bridge, was isolated from Cannabis sativa. This is the first example of
      a C-bridged dimeric cannabinoid. The structure of 1 was unambiguously deduced by
      HRESIMS, GCMS, and NMR spectroscopy. A plausible biogenesis of 1 is described.

PMID- 27695142
TI  - Exploiting Dual Otoacoustic Emission Sources.
AB  - Two distinct processes generate otoacoustic emissions (OAEs). Reflection-source
      emissions, here recorded as stimulus frequency OAEs, are optimally informative at
      low sound levels and are more sensitive to slight hearing loss; they have been
      linked to cochlear amplifier gain and tuning. Distortion-source emissions are
      strongest at moderate-high sound levels and persist despite mild hearing loss;
      they likely originate in the nonlinear process of hair cell transduction. In this
      preliminary study, we exploit the unique features of each by generating a
      combined reflection-distortion OAE profile in normal hearing and hearing-impaired
      ears. Distortion-product (DP) and stimulus-frequency (SF) OAEs were recorded over
      a broad range of stimulus levels and frequencies. Individual I/O and transfer
      functions were generated for both emission types in each ear, and OAE peak
      strength, compression threshold, and rate of compression were calculated. These
      combined SFOAE and DPOAE features in normal and hearing-impaired ears may provide
      a potentially informative and novel index of hearing loss. This is an initial
      step toward utilizing OAE source in characterizing cochlear function and
      dysfunction.

PMID- 27695143
TI  - Discriminant Analysis of Time Series in the Presence of Within-Group Spectral
      Variability.
AB  - Many studies record replicated time series epochs from different groups with the
      goal of using frequency domain properties to discriminate between the groups. In
      many applications, there exists variation in cyclical patterns from time series
      in the same group. Although a number of frequency domain methods for the
      discriminant analysis of time series have been explored, there is a dearth of
      models and methods that account for within-group spectral variability. This
      article proposes a model for groups of time series in which transfer functions
      are modeled as stochastic variables that can account for both between-group and
      within-group differences in spectra that are identified from individual
      replicates. An ensuing discriminant analysis of stochastic cepstra under this
      model is developed to obtain parsimonious measures of relative power that
      optimally separate groups in the presence of within-group spectral variability.
      The approach possess favorable properties in classifying new observations and can
      be consistently estimated through a simple discriminant analysis of a finite
      number of estimated cepstral coefficients. Benefits in accounting for within
      group spectral variability are empirically illustrated in a simulation study and
      through an analysis of gait variability.

PMID- 27695144
TI  - The Effect of mGluR5 Antagonism During Binge Drinkingon Subsequent Ethanol Intake
      in C57BL/6J Mice: Sex- and Age-Induced Differences.
AB  - BACKGROUND: Binge ethanol (EtOH) intake during adolescence leads to an array of
      behavioral and cognitive consequences including elevated intake of EtOH during
      adulthood, with female mice showing greater susceptibility than males.
      Administration of the metabotropic glutamate receptor 5 (mGluR5) antagonist 3-((2
      Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) has been shown to reduce EtOH
      self-administration in adult male mice, but little is known about its effect on
      female and adolescent mice. METHODS: MTEP (0, 10, 20 mg/kg, i.p.) was repeatedly
      administered to female and male, adult and adolescent C57BL/6J mice during binge
      sessions using the scheduled high alcohol consumption paradigm. Next, we assessed
      whether MTEP administration during binge altered the subsequent 24-hour EtOH
      intake following a period of abstinence. Finally, we investigated whether MTEP
      administration during binge followed by an abstinence period altered mRNA of
      glutamatergic genes within the nucleus accumbens of female mice. RESULTS: MTEP
      significantly decreased binge EtOH intake in all mice, but only female mice
      exhibited altered subsequent 24-hour EtOH intake. Interestingly, the alteration
      in subsequent EtOH intake in female animals was age dependent, with adolescent
      exposure to MTEP during binge decreasing 24-hour intake and adult exposure to
      MTEP during binge increasing 24-hour intake. Finally, while there were no effects
      of MTEP pretreatment on the genes examined, there was a robust age effect found
      during analysis of mGluR1 (Grm1), mGluR5 (Grm5), the NR2A subunit of the NMDA
      receptor (Grin2a), phosphatidylinositol 3-kinase (Pik3r1), mammalian target of
      rapamycin (Mtor), and extracellular signal-regulated kinase (Mapk1) mRNA, with
      adolescent female animals having lower expression than their adult counterparts.
      CONCLUSIONS: Collectively, the present findings add to existing evidence
      implicating the contribution of long-term effects of adolescent binge drinking to
      enhance alcohol abuse in adulthood, while suggesting that mGluR5 antagonism may
      not be the best pharmacotherapy to treat binge alcohol consumption in female and
      adolescent animals.

PMID- 27695146
TI  - Stress-Related Symptoms and Suicidal Ideation: The Roles of Rumination and
      Depressive Symptoms Vary by Gender.
AB  - There is a growing body of literature suggesting that reactions to stressful life
      events, such as intrusive thoughts, physiological hyperarousal, and
      cognitive/behavioral avoidance (i.e., stress-related symptoms) may increase risk
      for thinking about and attempting suicide. Cognitive vulnerability models have
      identified rumination (i.e., perseverating on a negative mood) as a maladaptive
      response that may increase risk for suicidal behavior, as it has also been linked
      to depression. The present study examined the direct and indirect effects of
      stress-related symptoms on suicidal ideation through rumination and depressive
      symptoms. Participants were 1375 young adults, primarily non-White (78 %) females
      (72 %), recruited from a public university in the Northeastern U.S., who
      completed measures of stress-related symptoms (as a response to a stressful
      event), rumination, depressive symptoms, and suicidal ideation. The relation
      between stress-related symptoms and suicidal ideation was accounted for by the
      brooding subtype of rumination and depressive symptoms among females. Depressive
      symptoms, but not rumination, better accounted for suicidal ideation among males.
      These findings suggest that the role of brooding and depressive symptoms in the
      relationship between stress-related symptoms and suicidal ideation may vary by
      gender.

PMID- 27695147
TI  - One-Parent Families in Contemporary Cambodia.
AB  - Non-marital births and divorce remain rare in Cambodia. Due to dramatic levels of
      adult mortality reached during the late 1970s, growing up with a single parent is
      not. Using nationally representative, cross-sectional data, we estimate that
      about 12% of children under age 18 co-reside with only one of their biological
      parents. Using longitudinal data representative of the Mekong River Valley, we
      find this proportion to be declining. Nearly half of these children live in
      nuclear families (single parent with or without a step-parent), even though they
      live in multigenerational families more frequently than children who live with
      both their parents, especially, when young and not living with their mother.
      Last, we consider differences in socioeconomic conditions and child educational
      outcomes by number of co-residing parents.

PMID- 27695145
TI  - Childhood Maltreatment Exposure and Disruptions in Emotion Regulation: A
      Transdiagnostic Pathway to Adolescent Internalizing and Externalizing
      Psychopathology.
AB  - Child maltreatment is a robust risk factor for internalizing and externalizing
      psychopathology in children and adolescents. We examined the role of disruptions
      in emotion regulation processes as a developmental mechanism linking child
      maltreatment to the onset of multiple forms of psychopathology in adolescents.
      Specifically, we examined whether child maltreatment was associated with
      emotional reactivity and maladaptive cognitive and behavioral responses to
      distress, including rumination and impulsive behaviors, in two separate samples.
      We additionally investigated whether each of these components of emotion
      regulation were associated with internalizing and externalizing psychopathology
      and mediated the association between child maltreatment and psychopathology.
      Study 1 included a sample of 167 adolescents recruited based on exposure to
      physical, sexual, or emotional abuse. Study 2 included a sample of 439
      adolescents in a community-based cohort study followed prospectively for 5 years.
      In both samples, child maltreatment was associated with higher levels of
      internalizing psychopathology, elevated emotional reactivity, and greater
      habitual engagement in rumination and impulsive responses to distress. In Study
      2, emotional reactivity and maladaptive responses to distress mediated the
      association between child maltreatment and both internalizing and externalizing
      psychopathology. These findings provide converging evidence for the role of
      emotion regulation deficits as a transdiagnostic developmental pathway linking
      child maltreatment with multiple forms of psychopathology.

PMID- 27695148
TI  - Pilot-scale spiral wound membrane assessment for THM precursor rejection from
      upland waters.
AB  - The outcomes of a pilot-scale study of the rejection of trihalomethanes (THMs)
      precursors by commercial ultrafiltration/nanofiltration (UF/NF) spiral-wound
      membrane elements are presented based on a single surface water source in
      Scotland. The study revealed the expected trend of increased flux and
      permeability with increasing pore size for the UF membranes; the NF membranes
      provided similar fluxes despite the lower nominal pore size. The dissolved
      organic carbon (DOC) passage decreased with decreasing molecular weight cut-off,
      with a less than one-third the passage recorded for the NF membranes than for the
      UF ones. The yield (weight % total THMs per DOC) varied between 2.5% and 8%
      across all membranes tested, in reasonable agreement with the literature, with
      the aromatic polyamide membrane providing both the lowest yield and lowest DOC
      passage. The proportion of the hydrophobic (HPO) fraction removed was found to
      increase with decreasing membrane selectivity (increasing pore size), and THM
      generation correlated closely (R2 = 0.98) with the permeate HPO fractional
      concentration.

PMID- 27695149
TI  - Rerandomization to Balance Tiers of Covariates.
AB  - When conducting a randomized experiment, if an allocation yields treatment groups
      that differ meaningfully with respect to relevant covariates, groups should be
      rerandomized. The process involves specifying an explicit criterion for whether
      an allocation is acceptable, based on a measure of covariate balance, and
      rerandomizing units until an acceptable allocation is obtained. Here we
      illustrate how rerandomization could have improved the design of an already
      conducted randomized experiment on vocabulary and mathematics training programs,
      then provide a rerandomization procedure for covariates that vary in importance,
      and finally offer other extensions for rerandomization, including methods
      addressing computational efficiency. When covariates vary in a priori importance,
      better balance should be required for more important covariates. Rerandomization
      based on Mahalanobis distance preserves the joint distribution of covariates, but
      balances all covariates equally. Here we propose rerandomizing based on
      Mahalanobis distance within tiers of covariate importance. Because balancing
      covariates in one tier will in general also partially balance covariates in other
      tiers, for each subsequent tier we explicitly balance only the components
      orthogonal to covariates in more important tiers.

PMID- 27695150
TI  - Technology and Communications Coursework: Facilitating the Progression of
      Students with Learning Disabilities through High School Science and Math
      Coursework.
AB  - Students identified with learning disabilities experience markedly lower levels
      of science and mathematics achievement than students who are not identified with
      a learning disability. Seemingly compounding their disadvantage, students with
      learning disabilities also complete more credits in non-core coursework
      traditionally considered non-academic coursework-than students who are not
      identified with a learning disability. The Education Longitudinal Study of 2002,
      a large national dataset with both regular and special education high school
      students, is utilized to determine whether credit accumulation in certain types
      of non-core coursework, such as Technology and Communications courses, is
      associated with improved science and math course-taking outcomes for students
      with learning disabilities. Results show that credit accumulation in Technology
      and Communications coursework uniquely benefits the science course-taking, and
      comparably benefits the math course-taking, of students identified with learning
      disabilities in contrast to students who are not identified with a learning
      disability.

PMID- 27695151
TI  - Effect of rate of pyrolysis on the textural properties of naturally-templated
      porous carbons from alginic acid.
AB  - The effect of pyrolysis rate on the properties of alginic acid-derived
      carbonaceous materials, termed Starbon(r), was investigated. Thermal Gravimetry
      IR was used to prepare porous carbons up to 800  degrees C at several rates and
      highlighted increased CO2 production at higher pyrolysis rates. N2 porosimetry of
      the resultant carbons shows how pyrolysis rate affects both the mesopore
      structure and thus surface area and surface energy. Surface capacity of these
      carbons was analysed by methylene blue dye adsorption. In general, as the rate of
      pyrolysis increased, the mesopore content and adsorbent capacity decreased. It is
      considered here that the rapid production of volatiles at these higher rates
      causes structural collapse of the non-templated pore network. The work here
      demonstrates that pyrolysis rate is a key variable which needs to be controlled
      to maximise the textural properties of Starbon(r) required for adsorption
      applications.

PMID- 27695153
TI  - Reconsidering the "acculturation gap" narrative through an analysis of parent
      adolescent acculturation differences in Mexican American families.
AB  - Using a sample of 193 Mexican American adolescents (M age at Wave 1 = 14) and
      three waves of data over two years, this study longitudinally examined the
      effects of parent-youth acculturation differences, relative to no differences, on
      parent-adolescent relationship quality and youth problem behavior. We examined
      parent-youth differences in overall acculturation, Mexican acculturation, and
      American acculturation. We differentiated between cases in which the adolescent
      was more acculturated than the parent and cases in which the parent was more
      acculturated than the adolescent. Adolescents were more commonly similar to their
      parents than different. Where differences existed, adolescents were not uniformly
      more American than their parents, no type of difference was associated with
      parent-adolescent relationship quality, and no type of difference in overall
      acculturation was associated with youth problem behavior. One type of difference
      by dimension (adolescent had less Mexican acculturation than mother) was
      associated with less risk of problem behavior.

PMID- 27695152
TI  - Solid-phase microextraction technology for in vitro and in vivo metabolite
      analysis.
AB  - Analysis of endogenous metabolites in biological samples may lead to the
      identification of biomarkers in metabolomics studies. To achieve accurate sample
      analysis, a combined method of continuous quick sampling and extraction is
      required for online compound detection. Solid-phase microextraction (SPME)
      integrates sampling, extraction and concentration into a single solvent-free step
      for chemical analysis. SPME has a number of advantages, including simplicity,
      high sensitivity and a relatively non-invasive nature. In this article, we
      reviewed SPME technology in in vitro and in vivo analyses of metabolites after
      the ingestion of herbal medicines, foods and pharmaceutical agents. The
      metabolites of microorganisms in dietary supplements and in the gastrointestinal
      tract will also be examined. As a promising technology in biomedical and
      pharmaceutical research, SPME and its future applications will depend on advances
      in analytical technologies and material science.

PMID- 27695154
TI  - Forecasting natural hazards, performance of scientists, ethics, and the need for
      transparency.
AB  - Landslides are one of several natural hazards. As other natural hazards,
      landslides are difficult to predict, and their forecasts are uncertain. The
      uncertainty depends on the poor understanding of the phenomena that control the
      slope failures, and on the inherent complexity and chaotic nature of the
      landslides. This is similar to other natural hazards, including hurricanes,
      earthquakes, volcanic eruptions, floods, and droughts. Due to the severe impact
      of landslides on the population, the environment, and the economy, forecasting
      landslides is of scientific interest and of societal relevance, and scientists
      attempting to forecast landslides face known and new problems intrinsic to the
      multifaceted interactions between science, decision-making, and the society. The
      problems include deciding on the authority and reliability of individual
      scientists and groups of scientists, and evaluating the performances of
      individual scientists, research teams, and their institutions. Related problems
      lay in the increasing subordination of research scientists to politics and
      decision-makers, and in the conceptual and operational models currently used to
      organize and pay for research, based on apparently objective criteria and
      metrics, considering science as any other human endeavor, and favoring science
      that produces results of direct and immediate application. The paper argues that
      the consequences of these problems have not been considered fully.

PMID- 27695155
TI  - Multi-Output Decision Trees for Lesion Segmentation in Multiple Sclerosis.
AB  - Multiple Sclerosis (MS) is a disease of the central nervous system in which the
      protective myelin sheath of the neurons is damaged. MS leads to the formation of
      lesions, predominantly in the white matter of the brain and the spinal cord. The
      number and volume of lesions visible in magnetic resonance (MR) imaging (MRI) are
      important criteria for diagnosing and tracking the progression of MS. Locating
      and delineating lesions manually requires the tedious and expensive efforts of
      highly trained raters. In this paper, we propose an automated algorithm to
      segment lesions in MR images using multi-output decision trees. We evaluated our
      algorithm on the publicly available MICCAI 2008 MS Lesion Segmentation Challenge
      training dataset of 20 subjects, and showed improved results in comparison to
      state-of-the-art methods. We also evaluated our algorithm on an in-house dataset
      of 49 subjects with a true positive rate of 0.41 and a positive predictive value
      0.36.

PMID- 27695156
TI  - Evaluation of a projection-domain lung nodule insertion technique in thoracic CT.
AB  - Task-based assessment of computed tomography (CT) image quality requires a large
      number of cases with ground truth. Inserting lesions into existing cases to
      simulate positive cases is a promising alternative approach. The aim of this
      study was to evaluate a recently-developed raw-data based lesion insertion
      technique in thoracic CT. Lung lesions were segmented from patient CT images,
      forward projected, and reinserted into the same patient CT projection data. In
      total, 32 nodules of various attenuations were segmented from 21 CT cases. Two
      experienced radiologists and 2 residents blinded to the process independently
      evaluated these inserted nodules in two sub-studies. First, the 32 inserted and
      the 32 original nodules were presented in a randomized order and each received a
      rating score from 1 to 10 (1=absolutely artificial to 10=absolutely realistic).
      Second, the inserted and the corresponding original lesions were presented side
      by-side to each reader, who identified the inserted lesion and provided a
      confidence score (1=no confidence to 5=completely certain). For the randomized
      evaluation, discrimination of real versus artificial nodules was poor with areas
      under the receiver operative characteristic curves being 0.69 (95% CI: 0.58
      0.78), 0.57 (95% CI: 0.46-0.68), and 0.62 (95% CI: 0.54-0.69) for the 2
      radiologists, 2 residents, and all 4 readers, respectively. For the side-by-side
      evaluation, although all 4 readers correctly identified inserted lesions in
      103/128 pairs, the confidence score was moderate (2.6). Our projection-domain
      based lung nodule insertion technique provides a robust method to artificially
      generate clinical cases that prove to be difficult to differentiate from real
      cases.

PMID- 27695157
TI  - The effects of compressive sensing on extracted features from tri-axial
      swallowing accelerometry signals.
AB  - Acquiring swallowing accelerometry signals using a comprehensive sensing scheme
      may be a desirable approach for monitoring swallowing safety for longer periods
      of time. However, it needs to be insured that signal characteristics can be
      recovered accurately from compressed samples. In this paper, we considered this
      issue by examining the effects of the number of acquired compressed samples on
      the calculated swallowing accelerometry signal features. We used tri-axial
      swallowing accelerometry signals acquired from seventeen stroke patients (106
      swallows in total). From acquired signals, we extracted typically considered
      signal features from time, frequency and time-frequency domains. Next, we
      compared these features from the original signals (sampled using traditional
      sampling schemes) and compressively sampled signals. Our results have shown we
      can obtain accurate estimates of signal features even by using only a third of
      original samples.

PMID- 27695158
TI  - Reduction of Cortisol Levels and Participants' Responses Following Art Making.
AB  - This quasi-experimental study investigated the impact of visual art making on the
      cortisol levels of 39 healthy adults. Participants provided saliva samples to
      assess cortisol levels before and after 45 minutes of art making. Participants
      also provided written responses about the experience at the end of the session.
      Results indicate that art making resulted in statistically significant lowering
      of cortisol levels. Participants' written responses indicated that they found the
      art-making session to be relaxing, enjoyable, helpful for learning about new
      aspects of self, freeing from constraints, an evolving process of initial
      struggle to later resolution, and about flow/losing themselves in the work. They
      also reflected that the session evoked a desire to make art in the future. There
      were weak associations between changes in cortisol level and age, time of day,
      and participant responses related to learning about one's self and references to
      an evolving process in art making. There were no significant differences in
      outcomes based on prior experiences with art making, media choice, or gender.

PMID- 27695159
TI  - Characterization of Obesity in the Prader-Labhart-Willi Syndrome: Fatness
      Patterning.
AB  - A multidisciplinary study involving cytogenetic, clinical, and anthropometric
      assessments of Prader-Labhart-Willi Syndrome (PLWS) has focused on improving
      diagnosis and prognosis in this complex condition. Since one of the major
      features of PLWS is obesity, 7 of the 26 measurements in the anthropometric
      evaluation were skinfold thicknesses at different body sites. Forty individuals
      with PLWS have been assessed. Z-scores were computed for skinfold measurements to
      examine quantitative differences for fatness at different sites. Data on PLWS
      individuals, grouped by age, sex, and chromosome type, were compared with
      normative data for skinfolds. The results suggest that males with PLWS have three
      times the fatness scores of other males their age, while scores for PLWS females
      average only twice those of normals. Our research illustrates the utility of
      anthropometry in the evaluation of patients in clinical genetics and offers a
      comprehensive approach to the heterogeneity observed in PLWS.

PMID- 27695161
TI  - Sleep's Kernel: Surprisingly small sections of brain, and even neuronal and glial
      networks in a dish, display many electrical indicators of sleep.

PMID- 27695160
TI  - Declines in Crime and Teen Childbearing: Identifying Potential Explanations for
      Contemporaneous Trends.
AB  - OBJECTIVES: The previous 25 years have witnessed remarkable upheavals in the
      social landscape of the United States. Two of the most notable trends have been
      dramatic declines in levels of crime as well as teen childbearing. Much remains
      unknown about the underlying conditions that might be driving these changes. More
      importantly, we do not know if the same distal factors that are responsible for
      the drop in the crime rate are similarly implicated in falling rates of teen
      births. We examine four overarching potential explanations: fluctuations in
      economic opportunity, shifting population demographics, differences in state
      level policies, and changes in expectations regarding health and mortality.
      METHODS: We combine state-specific data from existing secondary sources and model
      trajectories of violent crime, homicides, robberies, and teen fertility over a 20
      year period from 1990 to 2010 using simultaneous fixed-effects regression models.
      RESULTS: We find that 4 of the 21 predictors examined - growth in the service
      sector of the labor market, increasing racial diversity especially among
      Hispanics, escalating levels of migration, and the expansion of family planning
      services to low-income women - offer the most convincing explanations for why
      rates of violent crime and teen births have been steadily decreasing over time.
      Moreover, we are able to account for almost a quarter of the joint declines in
      violent crime and teen births. CONCLUSIONS: Our conclusions underscore the far
      reaching effects that aggregate level demographic conditions and policies are
      likely to have on important social trends that might, at first glance, seem
      unrelated. Furthermore, the effects of policy efforts designed to target outcomes
      in one area are likely to spill over into other domains.

PMID- 27695162
TI  - NORMATIVE STANDARDS AND COMPARISON OF ANTHROPOMETRIC DATA OF WHITE AND BLACK
      NEWBORN INFANTS.
AB  - We report normative standards for length, weight, 17 craniofacial dimensions, 5
      hand and foot measurements, 7 circumferences, 9 skinfold thicknesses, penile
      length, and testicular volume in black and white newborns. No significant
      differences in these variables were found between black males and females. White
      males had greatest craniofacial height, head length, head breadth, minimum
      frontal diameter, bizygomatic diameter, and head circumference, whereas white
      females had largest medial calf, thigh, forearm, and subscapular skinfolds. White
      infants had largest weight, head circumference, head length, head breadth, calf
      and chest circumferences, and medial calf and forearm skinfolds, whereas nose
      breadth, mouth breadth, and penile length were greatest in black newborns.

PMID- 27695163
TI  - Development and testing of Baylor Scott & White Health's "Attitudes and Practices
      of Patient Safety Survey".
AB  - Improving the quality of patient care requires a culture attuned to safety. We
      describe the development, implementation, and psychometric evaluation of the
      Attitudes and Practices of Patient Safety Survey (APPSS) within the Baylor Scott
      & White Health system. The APPSS was designed to enable safety culture data to be
      collected and aggregated at the unit level to identify high-priority needs. The
      survey, with 27 Likert-scale core questions divided into 4 concept domains and 2
      open-ended questions, was administered electronically to employees with direct
      patient care responsibilities (n = 16,950). The 2015 response rate was 50.4%. The
      Cronbach's alpha values for the four domains ranged from 0.78 to 0.90, indicating
      strong internal consistency. Confirmatory factor analysis results were mixed but
      were comparable to those of established safety culture surveys. Over the years,
      the adaptability of the APPSS has proven helpful to administrative and clinical
      leaders alike, and the survey responses have led to the creation of programs to
      improve the organization's patient safety culture. In conclusion, the APPSS
      provides a reliable measure of patient safety culture and may be useful to other
      health care organizations seeking to improve the quality and safety of the care
      they provide.

PMID- 27695164
TI  - Safety and efficacy of 2-octyl-cyanoacrylate in the management of patients with
      gastric and duodenal varices who are not candidates for transjugular intrahepatic
      portosystemic shunts.
AB  - Gastric variceal bleeding is associated with significant morbidity and mortality
      in patients with portal hypertension and cirrhosis. Options are limited for
      patients who are not candidates for transjugular intrahepatic portosystemic
      shunts (TIPS). Cyanoacrylate injections have been reported to be efficacious in
      previous case series. The aim of this retrospective study was to report our
      single-center experience with the safety and efficacy of 2-octyl-cyanoacrylate in
      patients who were not TIPS candidates. Electronic medical records were reviewed
      for 16 patients who underwent a total of 18 esophagogastroduodenoscopies for
      acute gastric or duodenal variceal bleeding and secondary prophylaxis of gastric
      varices; 14 patients had cirrhosis with an average Model for End-Stage Liver
      Disease score of 16, and 2 patients had noncirrhotic portal hypertension. Primary
      endpoints of the study included early and delayed rebleeding rate, complications,
      and death or liver transplantation. The rebleeding rate (early or delayed) was
      7%, and no complications were found. One death was reported (unrelated to the
      procedure). In conclusion, 2-octyl-cyanoacrylate is a safe and effective
      alternative for non-TIPS candidates who present with acute gastric variceal
      bleeding given its low rebleeding and complication rate.

PMID- 27695165
TI  - Usefulness of ultrasonographic measurement of the diameter of the inferior vena
      cava to predict responsiveness to intravascular fluid administration in patients
      with cancer.
AB  - We conducted an observational, longitudinal prospective study in which we
      measured the diameters of the inferior vena cava (IVC) of 47 patients using
      ultrasonography. The aim of our study was to assess the state of blood volume and
      to determine the percentage of patients who responded to intravascular volume
      expansion. Only 17 patients (36%) responded to fluid management. A higher number
      of responding patients had cardiovascular failure compared with nonresponders
      (82% vs. 50%, P = 0.03). Among the patients with cardiovascular failure, the
      probability of finding responders was 4.6 times higher than that of not finding
      responders (odds ratio, 4.66; 95% confidence interval, 1.10-19.6; P = 0.04). No
      significant difference was observed in the mortality rate between the two groups
      (11% vs. 23%, P = 0.46). In conclusion, responding to intravascular volume
      expansion had no impact on patient survival in the intensive care unit.

PMID- 27695166
TI  - Selection of abstracts from the 4th annual Baylor Scott & White - Central Texas
      Research Days.

PMID- 27695167
TI  - Percutaneous gallbladder aspiration for acute cholecystitis.
AB  - Early cholecystectomy for patients with acute cholecystitis may not be possible
      in some clinical settings. Percutaneous gallbladder aspiration (PGBA) offers an
      alternative approach, but the benefits and risks of this procedure are unclear.
      We synthesized data on the outcomes of PGBA in acute cholecystitis patients using
      data sources from online databases, including MEDLINE and EMBASE, and
      bibliographies of included studies from January 2000 through December 2015. Two
      reviewers independently reviewed and critiqued the quality of each study. Seven
      eligible studies met our criteria. The success rates in single PGBA and
      repetitive PGBA (2-4 times) were 50% to 93% and 76% to 96%, respectively.
      Complication rates were 0% to 8% and were unrelated to the size of needle gauge
      used for aspiration and the number of aspirations. Salvage percutaneous
      cholecystostomy (PC) and urgent surgery were required in 0% to 43% of patients
      and 0% to 4% of patients, respectively. Two studies with antibiotic instillation
      had clinical success rates of 95% and 96%. In conclusion, repetitive PGBA
      combined with antibiotic instillation and salvage PC are useful alternatives to
      early cholecystectomy in patients with acute cholecystitis.

PMID- 27695168
TI  - Epidural analgesia complicated by dural ectasia in the Marfan syndrome.
AB  - Patients with the Marfan syndrome are considered to be high risk during pregnancy
      and warrant a complete multidisciplinary evaluation. One goal is to minimize
      hemodynamic fluctuations during labor since hypertensive episodes may result in
      aortic dissection or rupture. Although they may prevent these complications,
      neuraxial techniques may be complicated by dural ectasia. The case of a
      parturient with the Marfan syndrome and mild dural ectasia is presented. During
      attempted labor epidural placement, unintentional dural puncture occurred. A
      spinal catheter was used for adequate labor analgesia, and a resultant postdural
      puncture headache was alleviated by an epidural blood patch under fluoroscopic
      guidance.

PMID- 27695169
TI  - Bilateral congenital pseudoarthrosis of the clavicles in a newborn.
AB  - Bilateral congenital pseudoarthrosis of the clavicles is extremely rare. We
      report a case of this entity presenting in the neonatal period. We highlight the
      importance of the differential diagnosis when clavicular fracture shows no
      evidence of healing or occurs bilaterally.

PMID- 27695170
TI  - Wedgie-associated radiculitis in a quinquagenarian.
AB  - Wedgies-the upward yanking of another's underpants from the rear to wedge them
      between the buttocks-can be administered playfully, maliciously, or
      adventurously; at forces ranging from gentle to "atomic"; and with or without the
      foreknowledge or consent of the recipient. Wedgies have been documented
      anecdotally in the popular Internet literature, with chief emphasis on their
      sensation-seeking or momentary entertainment value to the giver and recipient.
      Most participants are typically young; however, we report the case of a 50-year
      old man who sustained chronic, painless radiculitis after he received an
      unanticipated wedgie of moderate force. This report-apparently the first of its
      kind in the medical literature-serves as notice that exchanging wedgies is not
      merely a juvenile act or immature prank: the outcome can be injurious.

PMID- 27695171
TI  - Synchronous trifocal colorectal cancer.
AB  - Synchronous colorectal cancers (SCRCs) have been increasingly diagnosed due to
      emerging diagnostic modalities. The presence of three or more synchronous
      colorectal cancers has, however, only rarely been reported. A 76-year-old white
      man presented for management of two concurrent colorectal adenocarcinomas in the
      left colon evidenced on total colonoscopy. Preoperative abdominal ultrasonography
      and thoracoabdominal computed tomography were negative for metastatic disease.
      The patient underwent an elective left hemicolectomy. The pathology report
      ultimately showed the presence of three moderately differentiated, distinct
      colorectal cancers. The patient experienced an uneventful recovery.

PMID- 27695172
TI  - Extreme anemia (hemoglobin 1.8 g/dL) secondary to colon cancer.
AB  - We present the case of a 34-year-old man who presented to the emergency
      department with complaints of generalized fatigue and palpitations, with a heart
      rate of approximately 100 beats per minute and an orthostatic blood pressure of
      80/30 mm Hg upon standing. A hemoglobin of 1.8 g/dL was discovered. A positive
      fecal occult blood test led to the diagnosis of colon cancer. Once the cancer was
      resected, the patient's anemia resolved.

PMID- 27695173
TI  - Acute myeloid leukemia presenting as galactorrhea.
AB  - Acute myeloid leukemia (AML) presents with symptoms related to pancytopenia
      (weakness, infections, bleeding diathesis) and organ infiltration with leukemic
      cells. Galactorrhea is an uncommon manifestation of AML. We report a case of AML
      presenting with galactorrhea.

PMID- 27695174
TI  - Acute promyelocytic leukemia after renal transplant and filgrastim treatment for
      neutropenia.
AB  - Prolonged immunosuppression in solid organ transplant recipients has been
      considered a risk for developing opportunistic infections and malignancies. Acute
      leukemia is a rare complication. We report a case of acute promyelocytic leukemia
      (APL) (FAB M3) after cadaveric renal transplant for focal segmental
      glomerulosclerosis in a 24-year-old woman. Her immunosuppressive therapy included
      tacrolimus, mycophenolate mofetil, and prednisone. Approximately 2 years after
      transplant, she became pancytopenic, prompting administration of filgrastim. A
      few doses caused a markedly increased blast count, resulting in a diagnosis of
      APL. She was successfully treated with all-trans-retinoic acid and arsenic
      trioxide. Myeloproliferative neoplasms after organ transplant or due to
      filgrastim are rare.

PMID- 27695175
TI  - Vanishing lung syndrome.
AB  - Giant bullae often mimic pneumothorax on radiographic appearance. We present the
      case of a 55-year-old man admitted to a referring hospital with dyspnea, cough,
      and increasing sputum production; he refused thoracotomy for tension pneumothorax
      and presented to our hospital for a second opinion. A computed tomography (CT)
      scan at our hospital revealed a giant bulla, which was managed conservatively as
      an exacerbation of chronic obstructive pulmonary disease. Thoracic surgery was
      consulted but advised against bullectomy. Giant bullae can easily be misdiagnosed
      as a pneumothorax, but the management of the two conditions is vastly different.
      Distinguishing between the two may require CT scan. Symptomatic giant bullae are
      managed surgically. We highlight the etiology, presentation, diagnosis, and
      treatment of bullous lung disease, especially in comparison to pneumothorax.

PMID- 27695176
TI  - Partial annular pancreas.
AB  - Annular pancreas is a developmental anomaly that can be associated with other
      conditions such as Down syndrome, duodenal atresia, and Hirschsprung disease. A
      band of pancreatic tissue, in continuity with the pancreatic head, completely or
      incompletely encircles the descending duodenum, sometimes assuming a "crocodile
      jaw" configuration. We present the case of an adult who presented with epigastric
      pain and vomiting and was found to have annular pancreas.

PMID- 27695177
TI  - Abdominal apoplexy resulting in small bowel obstruction.
AB  - Abdominal apoplexy is a rare hemorrhagic condition involving the small arteries
      or veins within the abdominal cavity. A high degree of clinical suspicion,
      followed by appropriate diagnostic workup and therapeutic intervention, is
      critical, as nonoperative mortality approaches 100%. Contrary to most previously
      reported cases, which were associated with hemoperitoneum, we present a patient
      in which gastroduodenal artery dissection resulted in an organized
      retroperitoneal hematoma with local compression of the duodenum and subsequent
      bowel obstruction, resulting in vomiting, aspiration, and death.

PMID- 27695178
TI  - Fulminant ulcerative colitis complicated by treatment-refractory bacteremia.
AB  - Severe ulcerative colitis is defined by more than six bloody stools daily and
      evidence of toxicity, demonstrated by fever, tachycardia, anemia, or an elevated
      erythrocyte sedimentation rate. Fulminant disease represents a subset of severe
      disease with signs and symptoms suggestive of increased toxicity. Treatment of
      severe colitis includes intravenous corticosteroid administration, with
      consideration of intravenous infliximab 5 mg/kg. Failure to show improvement
      after 3 to 5 days is an indication for colectomy or treatment with intravenous
      cyclosporine. We report a 23-year-old Hispanic woman with decompensated cirrhosis
      presenting with new-onset fulminant ulcerative colitis and resulting
      polymicrobial bacteremia, requiring colectomy for infection source control and
      colitis treatment.

PMID- 27695179
TI  - Isolated naratriptan-associated ischemic colitis.
AB  - We report a 41-year-old woman who developed histology- and colonoscopy-proven
      ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a
      day and 3 days per week and without a known medical or cardiovascular history. By
      exclusion of other causes of colonic ischemia, naratriptan was considered the
      sole causal agent. Discontinuation of naratriptan resulted in a complete clinical
      recovery. To date, our patient is the youngest known patient to develop ischemic
      colitis on isolated naratriptan in the setting of no known medical risk factors
      or predisposing medical condition. Even though triptans are commonly used for the
      abortive treatment of migraine headaches, such a reported side effect is rare;
      however, careful assessment and individual patient-based treatment is advised.

PMID- 27695180
TI  - Acute renal failure due to vancomycin toxicity in the setting of unmonitored
      vancomycin infusion.
AB  - Vancomycin-induced nephrotoxicity is a commonly feared and largely preventable
      adverse effect of vancomycin therapy. We present the case of a 56-year-old woman
      who developed acute renal failure requiring hemodialysis as a result of
      unmonitored vancomycin infusions for the treatment of osteomyelitis.

PMID- 27695181
TI  - Hemopericardium with tamponade following rivaroxaban administration and its
      attenuation by CYP3A4 inhibitors.
AB  - Novel oral anticoagulants including the factor Xa inhibitor rivaroxaban are
      important alternatives to warfarin for the prevention of thromboembolic stroke in
      patients with nonvalvular atrial fibrillation. The pharmacology and metabolism of
      these agents differ from those of the vitamin K antagonists used over the decades
      preceding their introduction. We present a case of spontaneous hemopericardium
      and cardiac tamponade following administration of rivaroxaban. A review of the
      patient's medications revealed a total of seven agents known to be metabolized
      through cytochrome P450 3A4 (CYP3A4), the major pathway for rivaroxaban
      metabolism. While most physicians are familiar with recommendations to monitor
      renal function in patients prescribed rivaroxaban, we suspect that many fail to
      evaluate possible interactions with other agents having CYP3A4 inhibitory or
      inducer activity.

PMID- 27695182
TI  - Management of a renal fungal bezoar caused by multidrug-resistant Candida
      glabrata.
AB  - We describe our management of an immunocompetent individual who developed
      obstructive uropathy and candidemia as a result of a fungal bezoar in the kidney.
      These sequelae arose from candiduria, provoked after several courses of
      antibiotics. Successful treatment included therapy with both culture-appropriate
      intravenous antifungals and operative intervention, including direct irrigation
      of the affected kidney with amphotericin B, relief of renal obstruction with a
      ureteral stent, a percutaneous nephrostomy tube, and ultimately endoscopic
      removal of the fungal bezoar. Our patient was successfully treated as evidenced
      by negative urine culture and lack of ongoing symptomatology.

PMID- 27695183
TI  - Lymphogranuloma venereum proctitis.
AB  - We describe a 60-year-old man who presented with rectal pain and bleeding of a
      month's duration. His presentation was highly suggestive of lymphogranuloma
      venereum (LGV) proctitis. Nucleic acid amplification for chlamydia and gonorrhea
      via rectal swab revealed evidence supportive of anorectal chlamydia. Treatment
      with doxycycline resulted in complete resolution of his symptoms.

PMID- 27695184
TI  - Placement of the AbbVie PEG-J tube for the treatment of Parkinson's disease in
      the interventional radiology suite.
AB  - The primary treatment for Parkinson's disease is dopaminergic stimulation.
      Although levodopa has historically been administered orally, maintaining a
      predictable plasma concentration of the drug is challenging. As a result, enteral
      administration of carbidopa/levodopa (Duopa) has emerged as a promising tool in
      the treatment of the disease. This requires placement of an enteric catheter, two
      of which have been approved by the Food and Drug Administration for delivery of
      Duopa. The approved tubes are placed using the "peroral" or "pull" technique, a
      method traditionally requiring endoscopy. This technical note describes placement
      of the AbbVie PEG-J tube by means of the peroral route while utilizing only
      sonographic and fluoroscopic guidance. After placing an orogastric tube and
      achieving percutaneous access to the stomach under fluoroscopic visualization, a
      snare catheter is advanced through the percutaneous access into the stomach. The
      orogastric tube is engaged with the snare and retracted, bringing the attached
      snare with it to the mouth. The AbbVie PEG tube is attached to the snare, pulled
      back down the esophagus and into the stomach before being retracted through the
      percutaneous access to the skin. Finally, the AbbVie J tube is advanced through
      the gastrostomy tube into the proximal jejunum and attached with the provided
      connectors. As demonstrated, the AbbVie PEG-J tube can be placed safely and
      effectively using a percutaneous image-guided technique without the use of an
      endoscope.

PMID- 27695185
TI  - Origin of the left subclavian artery as the first branch and origin of the right
      subclavian artery as the fourth branch of the aortic arch with crisscrossing
      posterior to the common carotid arteries.
AB  - We describe an aortic arch anomaly consisting of the origin of the left
      subclavian artery as the fourth branch and the right subclavian artery as the
      first branch off the aortic arch with crisscrossing of these two arteries
      anterior to the trachea without clinical consequences. This anomaly, to our
      knowledge, has not been reported previously.

PMID- 27695186
TI  - Frequency and potential consequences of origin of the left vertebral artery (or
      the arteria thryoidea ima) directly from the aortic arch.
AB  - Described herein are findings in a 58-year-old man in whom necropsy disclosed
      origin of the left vertebral artery (or the arteria thryoidea ima) directly from
      the aortic arch. No functional consequences resulted. Study of previous
      publications disclosed the frequency of this anomaly in adults to be
      approximately 3.5%. Dissection has been reported to be more frequent in the left
      vertebral artery when it arises directly from the aorta than when it arises from
      the left subclavian artery.

PMID- 27695187
TI  - Left atrial myxoma masquerading as viral flu.
AB  - Atrial myxoma is a rare cardiac tumor that may be diagnosed incidentally on
      cardiac imaging or may present with life-threatening cardiac symptoms. We present
      a case of giant left atrial myxoma that presented as a flulike illness.

PMID- 27695188
TI  - Melanoma to the heart.
AB  - Malignant melanoma is the third most common skin cancer yet has the highest
      mortality rate due to its predilection for metastasis. While the diagnosis of
      antemortem melanoma with cardiac metastasis is relatively uncommon, diagnosing
      malignant melanoma itself by first identifying a cardiac metastasis is even more
      rare. This vignette describes an antemortem diagnosis of melanoma in a 50-year
      old woman through identification of metastasis to multiple sites, including the
      tricuspid valve.

PMID- 27695189
TI  - New-onset retrosternal chest pressure.

PMID- 27695190
TI  - Epipericardial fat necrosis as a cause of acute chest pain.
AB  - Acute chest pain is one of the most common reasons for presentation to the
      emergency department. Although most etiologies of chest pain are easy to
      clinically ascertain with routine history, physical, and laboratory examinations,
      we present an important benign cause of acute chest pain that may mimic acute
      coronary syndrome.

PMID- 27695191
TI  - Facts and ideas from anywhere.

PMID- 27695192
TI  - An Actively Decoupled Dual Transceiver Coil System for Continuous ASL at 7 T.
AB  - 7 T arterial spin labeling (ASL) faces major challenges including the increased
      specific absorption rate (SAR) and increased B0 and B1 inhomogeneity. This work
      describes the design and implementation of a dual-coil system that allows for
      continuous ASL (CASL) at 7 T. This system consisted of an actively detunable
      eight-channel transceiver head coil, and a three-channel transceiver labeling
      coil. Four experiments were performed in 5 healthy subjects: (i) to demonstrate
      that active detuning during ASL labeling reduces magnetization transfer; (ii) to
      measure the B1 profile at the labeling plane; (iii) to quantify B0 off-resonance
      at the labeling plane; and (iv) to collect in vivo CASL data. The magnetization
      transfer ratio in the head coil was reduced to 0.0 +/- 0.2% by active detuning
      during labeling. The measured B1 profiles in all 5 subjects were sufficient to
      satisfy the flow-driven adiabatic inversion necessary for CASL, however the
      actual labeling efficiency was significantly impacted by B0 off-resonance at the
      labeling plane. The measured CASL percent signal change in gray matter (0.94% +/-
      0.10%) corresponds with the low labeling efficiency predicted by the B0 off
      resonance. This work demonstrates progress in the technical implementation of 7 T
      CASL, and reinforces the need for improved B0 homogeneity at the labeling plane.

PMID- 27695194
TI  - Emergence of PPR and its threat to Europe.
AB  - PPR is an important infectious viral disease of domestic and wild small
      ruminants, that threatens the food security and sustainable livelihood of farmers
      across Africa, the Middle East and Asia. Europe is free of the disease except in
      Thrace (European part of Turkey) and Israel where outbreaks occur. Following the
      successful eradication of RPV, PPR has been targeted by the OIE and FAO as the
      next viral pathogen to be eradicated by 2030. However, the recent outbreaks in
      Northen Africa and Thrace (European part of Turkey) represent a significant
      threat to mainland Europe, as a source of disease spread. We have discussed here
      the emergence of PPR worldwide since its discovery with particular reference to
      the recent outbreaks in Northen Africa and Thrace, and the potential for spread
      of the disease into Europe.

PMID- 27695193
TI  - How age of acquisition influences brain architecture in bilinguals.
AB  - In the present study, we explored how Age of Acquisition (AoA) of L2 affected
      brain structures in bilingual individuals. Thirty-six native English speakers who
      were bilingual were scanned with high resolution MRI. After MRI signal intensity
      inhomogeneity correction, we applied both voxel-based morphometry (VBM) and
      surface-based morphometry (SBM) approaches to the data. VBM analysis was
      performed using FSL's standard VBM processing pipeline. For the SBM analysis, we
      utilized a semi-automated sulci delineation procedure, registered the brains to
      an atlas, and extracted measures of twenty four pre-selected regions of interest.
      We addressed three questions: (1) Which areas are more susceptible to differences
      in AoA? (2) How do AoA, proficiency and current level of exposure work together
      in predicting structural differences in the brain? And (3) What is the direction
      of the effect of AoA on regional volumetric and surface measures? Both VBM and
      SBM results suggested that earlier second language exposure was associated with
      larger volumes in the right parietal cortex. Consistently, SBM showed that the
      cortical area of the right superior parietal lobule increased as AoA decreased.
      In contrast, in the right pars orbitalis of the inferior frontal gyrus, AoA,
      proficiency, and current level of exposure are equally important in accounting
      for the structural differences. We interpret our results in terms of current
      theory and research on the effects of L2 learning on brain structures and
      functions.

PMID- 27695196
TI  - Racial and Ethnic Infant Mortality Gaps and the Role of Socio-Economic Status.
AB  - We assess the extent to which differences in socio-economic status are associated
      with racial and ethnic gaps in a fundamental measure of population health: the
      rate at which infants die. Using micro-level Vital Statistics data from 2000 to
      2004, we examine mortality gaps of infants born to white, black, Mexican, Puerto
      Rican, Asian, and Native American mothers. We find that between-group mortality
      gaps are strongly and consistently (except for Mexican infants) associated with
      maternal marital status, education, and age, and that these same characteristics
      are powerful predictors of income and poverty for new mothers in U.S. Census
      data. Despite these similarities, we document a fundamental difference in the
      mortality gap for the three high mortality groups: whereas the black-white and
      Puerto Rican-white mortality gaps mainly occur at low birth weights, the Native
      American-white gap occurs almost exclusively at higher birth weights. We further
      examine the one group whose IMR is anomalous compared to the other groups:
      infants of Mexican mothers die at relatively low rates given their socio-economic
      disadvantage. We find that this anomaly is driven by lower infant mortality among
      foreign-born mothers, a pattern found within many racial/ethnic groups. Overall,
      we conclude that the infant mortality gaps for our six racial/ethnic groups
      exhibit many commonalities, and these commonalities suggest a prominent role for
      socio-economic differences.

PMID- 27695195
TI  - Mapping paddy rice planting area in cold temperate climate region through
      analysis of time series Landsat 8 (OLI), Landsat 7 (ETM+) and MODIS imagery.
AB  - Accurate and timely rice paddy field maps with a fine spatial resolution would
      greatly improve our understanding of the effects of paddy rice agriculture on
      greenhouse gases emissions, food and water security, and human health. Rice paddy
      field maps were developed using optical images with high temporal resolution and
      coarse spatial resolution (e.g., Moderate Resolution Imaging Spectroradiometer
      (MODIS)) or low temporal resolution and high spatial resolution (e.g., Landsat
      TM/ETM+). In the past, the accuracy and efficiency for rice paddy field mapping
      at fine spatial resolutions were limited by the poor data availability and image
      based algorithms. In this paper, time series MODIS and Landsat ETM+/OLI images,
      and the pixel- and phenology-based algorithm are used to map paddy rice planting
      area. The unique physical features of rice paddy fields during the flooding/open
      canopy period are captured with the dynamics of vegetation indices, which are
      then used to identify rice paddy fields. The algorithm is tested in the Sanjiang
      Plain (path/row 114/27) in China in 2013. The overall accuracy of the resulted
      map of paddy rice planting area generated by both Landsat ETM+ and OLI is 97.3%,
      when evaluated with areas of interest (AOIs) derived from geo-referenced field
      photos. The paddy rice planting area map also agrees reasonably well with the
      official statistics at the level of state farms (R2 = 0.94). These results
      demonstrate that the combination of fine spatial resolution images and the
      phenology-based algorithm can provide a simple, robust, and automated approach to
      map the distribution of paddy rice agriculture in a year.

PMID- 27695197
TI  - Special Education of Children with Fetal Alcohol Spectrum Disorder.
AB  - The current study aimed to estimate the cost associated with special education
      among children (5 to 14 years) with Fetal Alcohol Spectrum Disorder (FASD) in
      elementary and middle school by sex, age group, and province and territory in
      Canada. It was estimated that there were 6,520 students with FASD receiving
      special education in Canada in 2011-2012. The cost of special education among
      these students was 53.5 million Canadian dollars. Implications for decision- and
      policymakers, educational systems and school staff are discussed.

PMID- 27695199
TI  - Magnetically tuned, robust and efficient filtering system for spatially multimode
      quantum memory in warm atomic vapors.
AB  - Warm atomic vapor quantum memories are simple and robust, yet suffer from a
      number of parasitic processes which produce excess noise. For operating in a
      single-photon regime precise filtering of the output light is essential. Here, we
      report a combination of magnetically tuned absorption and Faraday filters, both
      light-direction insensitive, which stop the driving lasers and attenuate spurious
      fluorescence and four-wave mixing while transmitting narrowband Stokes and anti
      Stokes photons generated in write-in and readout processes. We characterize both
      filters with respect to adjustable working parameters. We demonstrate a
      significant increase in the signal-to-noise ratio upon applying the filters seen
      qualitatively in measurements of correlation between the Raman scattered photons.

PMID- 27695200
TI  - Quantum memory receiver for superadditive communication using binary coherent
      states.
AB  - We propose a simple architecture based on multimode quantum memories for
      collective readout of classical information keyed using a pair coherent states,
      exemplified by the well-known binary phase shift keying format. Such a
      configuration enables demonstration of the superadditivity effect in classical
      communication over quantum channels, where the transmission rate becomes enhanced
      through joint detection applied to multiple channel uses. The proposed scheme
      relies on the recently introduced idea to prepare Hadamard sequences of input
      symbols that are mapped by a linear optical transformation onto the pulse
      position modulation format [Guha, S. Phys. Rev. Lett.2011, 106, 240502]. We
      analyze two versions of readout based on direct detection and an optional Dolinar
      receiver which implements the minimum-error measurement for individual detection
      of a binary coherent state alphabet.

PMID- 27695201
TI  - Internal short circuit and accelerated rate calorimetry tests of lithium-ion
      cells: Considerations for methane-air intrinsic safety and explosion
      proof/flameproof protection methods.
AB  - Researchers with the National Institute for Occupational Safety and Health
      (NIOSH) studied the potential for lithium-ion cell thermal runaway from an
      internal short circuit in equipment for use in underground coal mines. In this
      third phase of the study, researchers compared plastic wedge crush-induced
      internal short circuit tests of selected lithium-ion cells within methane (CH4)
      air mixtures with accelerated rate calorimetry tests of similar cells. Plastic
      wedge crush test results with metal oxide lithium-ion cells extracted from
      intrinsically safe evaluated equipment were mixed, with one cell model igniting
      the chamber atmosphere while another cell model did not. The two cells models
      exhibited different internal short circuit behaviors. A lithium iron phosphate
      (LiFePO4) cell model was tolerant to crush-induced internal short circuits within
      CH4-air, tested under manufacturer recommended charging conditions. Accelerating
      rate calorimetry tests with similar cells within a nitrogen purged 353-mL chamber
      produced ignitions that exceeded explosion proof and flameproof enclosure minimum
      internal pressure design criteria. Ignition pressures within a 20-L chamber with
      6.5% CH4-air were relatively low, with much larger head space volume and less
      adiabatic test conditions. The literature indicates that sizeable lithium thionyl
      chloride (LiSOCl2) primary (non rechargeable) cell ignitions can be especially
      violent and toxic. Because ignition of an explosive atmosphere is expected within
      explosion proof or flameproof enclosures, there is a need to consider the
      potential for an internal explosive atmosphere ignition in combination with a
      lithium or lithium-ion battery thermal runaway process, and the resulting effects
      on the enclosure.

PMID- 27695198
TI  - Quantum memories: emerging applications and recent advances.
AB  - Quantum light-matter interfaces are at the heart of photonic quantum
      technologies. Quantum memories for photons, where non-classical states of photons
      are mapped onto stationary matter states and preserved for subsequent retrieval,
      are technical realizations enabled by exquisite control over interactions between
      light and matter. The ability of quantum memories to synchronize probabilistic
      events makes them a key component in quantum repeaters and quantum computation
      based on linear optics. This critical feature has motivated many groups to
      dedicate theoretical and experimental research to develop quantum memory devices.
      In recent years, exciting new applications, and more advanced developments of
      quantum memories, have proliferated. In this review, we outline some of the
      emerging applications of quantum memories in optical signal processing, quantum
      computation and non-linear optics. We review recent experimental and theoretical
      developments, and their impacts on more advanced photonic quantum technologies
      based on quantum memories.

PMID- 27695202
TI  - Promise and Ontological Ambiguity in the In vitro Meat Imagescape: From
      Laboratory Myotubes to the Cultured Burger.
AB  - In vitro meat (IVM), also known as cultured meat, involves growing cells into
      muscle tissue to be eaten as food. The technology had its most high-profile
      moment in 2013 when a cultured burger was cooked and tasted in a press
      conference. Images of the burger featured in the international media and were
      circulated across the Internet. These images-literally marks on a two-dimensional
      surface-do important work in establishing what IVM is and what it can do. A
      combination of visual semiotics and narrative analysis shows that images of IVM
      afford readings of their story that are co-created by the viewer. Before the
      cultured burger, during 2011, images of IVM fell into four distinct categories:
      cell images, tissue images, flowcharts, and meat in a dish images. The narrative
      infrastructure of each image type affords different interpretations of what IVM
      can accomplish and what it is. The 2013 cultured burger images both draw upon and
      depart from these image types in an attempt to present IVM as a normal food
      stuff, and as 'matter in place' when placed on the plate. The analysis of
      individual images and the collection of images about a certain object or subject
      known as the imagescape-is a productive approach to understanding the ontology
      and promise of IVM and is applicable to other areas of social life.

PMID- 27695203
TI  - Estimating the health benefit of reducing indoor air pollution in a randomized
      environmental intervention.
AB  - Recent intervention studies targeted at reducing indoor air pollution have
      demonstrated both the ability to improve respiratory health outcomes and to
      reduce particulate matter (PM) levels in the home. However, these studies
      generally do not address whether it is the reduction of PM levels specifically
      that improves respiratory health. In this paper we apply the method of principal
      stratification to data from a randomized air cleaner intervention designed to
      reduce indoor PM in homes of children with asthma. We estimate the health benefit
      of the intervention amongst study subjects who would experience a substantial
      reduction in PM in response to the intervention. For those subjects we find an
      increase in symptom-free days that is almost three times as large as the overall
      intention-to-treat effect. We also explore the presence of treatment effects
      amongst those subjects whose PM levels would not respond to the air cleaner. This
      analysis demonstrates the usefulness of principal stratification for
      environmental intervention trials and its potential for much broader application
      in this area.

PMID- 27695204
TI  - Intracellular Organisms as Placental Invaders.
AB  - In this article we present a novel model for how the human placenta might get
      infected via the hematogenous route. We present a list of diverse placental
      pathogens, like Listeria monocytogenes or Cytomegalovirus, which are familiar to
      most obstetricians, but others, like Salmonella typhi, have only been reported in
      case studies or small case series. Remarkably, all of these organisms on this
      list are either obligate or facultative intracellular organisms. These pathogens
      are able to enter and survive inside host immune cells for at least a portion of
      their life cycle. We suggest that many blood-borne pathogens might arrive at the
      placenta via transportation inside of maternal leukocytes that enter the decidua
      in early pregnancy. We discuss mechanisms by which extravillous trophoblasts
      could get infected in the decidua and spread infection to other layers in the
      placenta. We hope to raise awareness among OB/GYN clinicians that organisms not
      typically associated with the TORCH list might cause placental infections and
      pregnancy complications.

PMID- 27695205
TI  - Gamma and Ion-Beam Irradiation of DNA: Free Radical Mechanisms, Electron Effects,
      and Radiation Chemical Track Structure.
AB  - The focus of our laboratory's investigation is to study the direct-type DNA
      damage mechanisms resulting from gamma-ray and ion-beam radiation-induced free
      radical processes in DNA which lead to molecular damage important to cellular
      survival. This work compares the results of low LET (gamma-) and high LET (ion
      beam) radiation to develop a chemical track structure model for ion-beam
      radiation damage to DNA. Recent studies on protonation states of cytosine cation
      radicals in the N1-substituted cytosine derivatives in their ground state and 5
      methylcytosine cation radicals in ground as well as in excited state are
      described. Our results exhibit a radical signature of excitations in 5
      methylcytosine cation radical. Moreover, our recent theoretical studies elucidate
      the role of electron-induced reactions (low energy electrons (LEE), presolvated
      electrons (epre-), and aqueous (or, solvated) electrons (eaq-)). Finally DFT
      calculations of the ionization potentials of various sugar radicals show the
      relative reactivity of these species.

PMID- 27695206
TI  - The long-term outcomes after staged repair of exstrophy-epispadias complex.
AB  - INTRODUCTION: Classic bladder exstrophy (BE) is a rare malformation of the genito
      urinary tract affecting 1:50,000 to 1:100,000 live births. The surgical
      reconstruction of the BE-epispadias complex is challenging for the most
      experienced pediatric urologists, surgeons, and orthopedists. PURPOSE: To assess
      the success of staged reconstruction of the BE and long-term effects on the upper
      urinary tract, renal function, and continence. MATERIALS AND METHODS: This is
      retrospective study; between 1994 and 2013, 30 patients with BE have undergone
      stage 1 repair at the institute. Eighteen male patients have been operated for
      epispadias repair and thirteen patients have undergone Guy Leadbetter bladder
      neck reconstruction. Three patients required augmentation cystoplasty one child
      is continent after epispadias repair only and one child attained continence after
      single-stage repair. RESULTS: Hence, out of 17 patients, 14 are socially
      continent, four patients require clean intermittent self-catheterization for
      bladder emptying. Four patients, who are coming for regular follow-up, are
      awaiting continence procedure. Two patients who underwent augmentation
      cystoplasty are on hemodialysis for renal failure and one child has altered renal
      function. CONCLUSION: In our experience, the modern staged repair offers a low
      risk of renal scarring with acceptable continence opportunity with acceptable
      cosmetic appearance of external genitalia in the males and females.

PMID- 27695207
TI  - Scrotal abscess: Varied etiology, associations, and management.
AB  - AIM: To report a series of scrotal abscess, a rare problem, their etiology, and
      management. MATERIALS AND METHODS: A retrospective study of children who
      presented with scrotal abscess between January 2010 and March 2015, analyzed with
      respect to clinical features, pathophysiology of spread and management. RESULTS:
      Eight infants and a 3-year-old phenotypically male child presented with scrotal
      abscess as a result of abdominal pathologies which included mixed gonadal
      dysgenesis (MGD) [1]; three anorectal malformations with ectopic ureter [1],
      urethral stricture [1], and neurogenic bladder [1]; meconium peritonitis with
      meconium periorchitis [2], ileal atresia [1], and intra-abdominal abscess [1];
      posturethroplasty for Y urethral duplication with metal stenosis [1] and
      idiopathic pyocele [1]. Transmission of the organism had varied routes include
      fallopian tube [1], urethra ejaculatory reflux [4], hematogenous [2], and the
      patent process of vaginalis [2]. Two of the nine required extensive evaluation
      for further management. Treating the predisposing pathology resolved scrotal
      abscesses in eight of nine patients, one of whom, required vasectomy
      additionally. Idiopathic pyocele responded to needle aspiration and antibiotics.
      CONCLUSION: Scrotal abscess needs a high index of suspicion for predisposing
      pathology, especially in infants. Laparoscopy is safe and effective in the
      management of the MGD and ectopic ureter.

PMID- 27695209
TI  - Intragastric pressure: Useful indicator in the management of congenital
      diaphragmatic hernia.
AB  - AIMS: To assess the role of measuring of intragastric pressure (IGP) during
      closure of congenital diaphragmatic hernia. MATERIALS AND METHODS: Thirty-two
      cases were included in the study (August 2008 to February 2014), and IGP has been
      measured intraoperatively during closure. RESULT: Patients were categorized in
      group A (15 patients), group B (14 patients) and group C (3 patients). In group
      C, IGP was more than 30 cm of water pressure and all of tehm required creation of
      ventral hernia and ventilator support. CONCLUSION: Measurement of IGP as an
      objective, noninvasive and simple method to evaluate intra-abdominal pressure and
      prevention of abdominal compartment syndrome and intraoperative IGP value
      determines the types of abdominal closure.

PMID- 27695208
TI  - Comparison of intravenous urography and magnetic resonance urography in
      preoperative evaluation of pelvi-ureteric junction obstruction in children.
AB  - AIMS: To compare intravenous urography (IVU) and magnetic resonance urography
      (MRU) in the preoperative evaluation of pelvi-ureteric junction obstruction
      (PUJO) in children. MATERIALS AND METHODS: A total of 35 children up to 10 years
      of age in whom unilateral or bilateral PUJO were suspected on ultrasonography
      were enrolled in this prospective study. All children underwent IVU and MRU, and
      the findings were compared. RESULTS: Of the 70 kidneys evaluated, 14 (20%) were
      not visualized on IVU because of nonexcretion of contrast, whereas all the 70
      (100%) kidneys were visualized on MRU. On IVU, nephrogram was not visualized in
      66 (94.2%) of the 70 kidneys, whereas MRU showed prompt and homogeneous
      nephrogram in 68 (97.1%) of the 70 kidneys. No evidence of PUJO was seen in 31
      (44.2%) kidneys on both IVU and MRU. IVU showed PUJO in 26 (37.1%) kidneys,
      whereas MRU showed it in 38 (54.2%) kidneys. MRU detected two duplex systems that
      were missed on IVU. A focal renal lesion and two incidental extra renal
      abnormalities were detected on MRU, which were not visualized on IVU. CONCLUSION:
      MRU is better than IVU, especially in case of poorly functioning kidneys which
      are not visualized on IVU. MRU also provides anatomic details of the ureter and
      vessels with better evaluation of renal parenchyma. It also has an additional
      advantage of detecting incidental extra renal abnormalities, if present.

PMID- 27695210
TI  - Gluteal teratoma: A rare site of extragonadal teratoma.
AB  - Extragonadal teratomas are rarely encountered in infants and children. These
      tumors are reported in retroperitoneum, floor of the mouth, mediastinum,
      craniofacial region or even in the solid organs of the body. Most of the gluteal
      teratomas reported in the literature are in fact, lateralized sacrococcygeal
      teratomas. We are reporting a case of unilateral big gluteal teratoma in a 6-year
      old girl. The tumor did not have any connection with the sacrum or coccyx and was
      successfully removed. Histology showed well-differentiated bowel as well as
      fetiform structures.

PMID- 27695211
TI  - Aggressive cervical neuroblastoma with a rare paraneoplastic syndrome: A
      therapeutic dilemma.
AB  - Neuroblastoma is infrequently associated with paraneoplastic syndromes. Amongst
      the few, opsomyoclonus (Kinsbourne syndrome) is the most common neurological
      paraneoplastic syndrome and diarrhea secondary to increased secretion of
      vasoactive intestinal peptide (Kerner-Morrison syndrome), hormonal paraneoplastic
      syndrome. Hypothalamic dysfunction (HD) is a rare disorder and its manifestation
      as a paraneoplastic syndrome of neuroblastoma is uncommonly reported. We present
      an interesting case of an unrelenting cervical neuroblastoma associated with HD,
      which posed a therapeutic challenge.

PMID- 27695212
TI  - Laparoscopic retrieval of unusual intra-abdominal foreign bodies in children.
AB  - Foreign body (FB) ingestion is a common problem among the pediatric population.
      On numerous occasions, the FB is left to pass out spontaneously without expecting
      any harm. There are instances when the FB is either to dangerous to be left
      alone, that is a button battery or a sharp object. There may be FB, which is
      either stuck in GIT or have migrated. The situation in these instances demand
      active intervention. The traditional option has been laparotomy and retrieval. We
      present here three cases where two needles and a belt buckle were removed by
      laparoscopy thus avoiding a laparotomy. These cases prove that laparoscopy should
      be the first choice for such kind of retrieval. These cases had a successful
      outcome with full recovery.

PMID- 27695213
TI  - Currarino syndrome: Rare clinical variants.
AB  - Currarino syndrome (CS) is a rare clinical condition. The classical presentation
      includes a triad of sacral anomaly, anorectal malformations, and presacral mass.
      This syndrome belongs to the group of persistent neuroenteric malformations. This
      article presents two cases of Currarino syndrome, where there was rare clinical
      variants such as rectal atresia in the first case and rectal stenosis in the
      second case. The clinical presentations were very deceptive as the first case
      presented as high anorectal malformation and the second case was simulating
      Hirschprung's disease.

PMID- 27695214
TI  - Inflammatory duodenal necrosis complicating gastroschisis.
AB  - Babies with gastroschisis have an increased risk of necrotizing enterocolitis
      (NEC) that can lead to short bowel syndrome, a long-term parenteral nutrition
      requirement, and its associated complications. To our knowledge, this is the
      first case report of recurrent duodenal ischemia and necrosis associated with
      gastroschisis in the absence of NEC totalis.

PMID- 27695215
TI  - Coexisting urogenital anomaly and duodenal atresia in two atypical Holt-Oram
      syndrome.
AB  - Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder, characterized by
      upper limb dysplasia and congenital cardiac defect. We report two cases with HOS,
      first associated with renal agenesis, coronal hypospadias, urethral duplication
      and second associated with duodenal atresia and horseshoe kidney that have not
      been reported in English literature.

PMID- 27695216
TI  - The role of laparoscopy in the identification and management of missing accessory
      spleens after primary splenectomy: A case report and literature review.
AB  - We present a 7-year-old boy with recurrent thrombocytopenia after primary
      laparoscopic splenectomy for immune thrombocytopenia (ITP). Imaging modalities
      (ultrasound, computed tomography scan, and scintigraphy) revealed two accessory
      spleens while the subsequent second laparoscopy revealed 11, which were
      successfully removed. The relevant medical literature is reviewed, and the value
      of laparoscopy for chronic ITP is highlighted.

PMID- 27695217
TI  - Congenital absence of appendix: A Surgeon's dilemma during surgery for acute
      appendicitis.
AB  - Congenital absence of the vermiform appendix is very rare in human beings with a
      reported incidence of 1 in 100,000 cases. Here, we report an incidence of a
      surgeon's dilemma to detect such a rare finding during surgery for a diagnosed
      case of acute appendicitis.

PMID- 27695218
TI  - Hickman to central venous catheter: A case of difficult venous access in a child
      suffering from acute lymphoblastic leukemia.
AB  - Chemotherapy in children suffering from cancer usually requires placement of an
      indwelling central venous catheter (CVC). A child may need to undergo repeated
      procedures because of infection and occlusion of previous access devices. We
      present a case of CVC insertion in a child suffering from acute lymphoblastic
      leukemia where an innovative technique was employed.

PMID- 27695219
TI  - Choledochal cyst with an aberrant right cholecysto-hepatic duct draining into
      cystic duct and a review of literature.

PMID- 27695220
TI  - Occult cysto-biliary communication: A forgotten complication of hepatic
      hydatidosis.

PMID- 27695221
TI  - Eventration of diaphragm with gastric perforation in a child: A rare
      presentation.

PMID- 27695222
TI  - Intensive care management of severe traumatic brain injury in India.

PMID- 27695223
TI  - Traumatic brain injury registry: Need of the hour.

PMID- 27695224
TI  - Neurosurgery in rural Nigeria: A prospective study.
AB  - BACKGROUND: Africa has very few neurosurgeons. These are almost exclusively in
      urban centers. Consequently, people in rural areas, most of the African
      population, have poor or no access to neurosurgical care. We have recently
      pioneered rural neurosurgery in Nigeria. OBJECTIVES: This report details our
      initial experiences and the profile of neurosurgical admissions in our center.
      METHODS: A prospective observational study of all neurosurgical patients managed
      at a rural tertiary health institution in Nigeria from December 2010 to May 2012
      was done. Simple descriptive data analysis was performed. RESULTS: A total of 249
      males (75.2%) and 82 females (24.8%) were managed. The median age was 37 years
      (range: Day of birth - 94 years). Trauma was the leading cause of presentation
      with 225 (68.0%) and 35 (10.6%) having sustained head and spinal injuries,
      respectively. Operative intervention was performed in 54 (16.3%). Twenty-four
      (7.2%) patients discharged against medical advice, mostly for economic reasons.
      Most patients (208, 63.4%) had satisfactory outcome while 30 (9.1%) died.
      CONCLUSION: Trauma is the leading cause of rural neurosurgical presentations.
      There is an urgent need to improve access to adequate neurosurgical care in the
      rural communities.

PMID- 27695225
TI  - Chemical shift magnetic resonance imaging in differentiation of benign from
      malignant vertebral collapse in a rural tertiary care hospital in North India.
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) is the modality of the first
      choice for evaluation of vertebral compression/collapse. Many MRI qualitative
      features help to differentiate benign from malignant collapse. We conducted this
      study to look for a quantitative difference in chemical shift values in benign
      and malignant collapse using dual-echo gradient echo in-phase/out-phase imaging.
      MATERIALS AND METHODS: MRI examinations of a total of 38 patients were
      retrospectively included in the study who had vertebral compression/collapse with
      marrow edema in which final diagnosis was available at the time of imaging/follow
      up. Signal intensity value in the region of abnormal marrow signal and adjacent
      normal vertebra was measured on in phase/out phase images. Signal intensity ratio
      (SIR) was measured by dividing signal intensity value on opposite phase images to
      that on in phase images. SIR was compared in normal vertebrae and benign and
      malignant vertebral collapse. RESULTS: There were 21 males and 17 females with
      mean age of 52.4 years (range 28-76 years). Out of total 38 patients, 18 were of
      benign vertebral collapse and 20 of malignant vertebral collapse. SIR in normal
      vertebrae was 0.30 +/- 0.14, 0.67 +/- 0.18 in benign vertebral collapse, and 1.20
      +/- 0.27 in malignant vertebral collapse with significant difference in SIR of
      normal vertebrae versus benign collapse (P < 0.01) and in benign collapse versus
      malignant collapse (P < 0.01). Assuming a cutoff of <0.95 for benign collapse and
      >=0.95 for malignant collapse, chemical shift imaging had a sensitivity of 90%
      and specificity of 94.4%. CONCLUSION: Chemical shift imaging is a rapid and
      useful sequence in differentiating benign from malignant vertebral collapse with
      good specificity and sensitivity.

PMID- 27695226
TI  - Longitudinal assessment of depression, stress, and burnout in medical students.
AB  - BACKGROUND: Medical students can and do suffer from mental disorders is a concept
      yet to get wide acceptance. There are few studies comprehensively evaluating
      depression, stress, and burnout in medical students, especially in a longitudinal
      way in India. The current study aims to assess the impact of medical education on
      the development of psychological morbidities and the role of personality.
      MATERIALS AND METHODS: First-year medical students of a leading medical college
      of India were enrolled on admission and given anonymized, validated, self
      administered questionnaires assessing depression, stress, burnout, and
      personality. This was repeated at the end of 1st year. Data were analyzed
      independently as questionnaires were anonymized. RESULTS: We found that 1st year
      of medical college showed a significantly increasing depression (P < 0.01) and
      stress (P < 0.01). Overall burnout did not increase significantly. However, only
      disengagement dimension of burnout increased significantly. Personalities with
      weak capacity to adjust had a significant positive correlation with depression (r
      = 0.277, P < 0.001) and stress scores (r = 0.210, P = 0.008). However, burnout
      did not correlate with any of the personality dimensions. CONCLUSION: Right from
      the 1st year of medical education students perceive high-stress levels and have a
      high risk of depression. Burnout starts to creep in at least in the form of
      disengagement. This study provides a sound groundwork for planning interventions
      to reduce student's mental morbidity and avoid burnout.

PMID- 27695227
TI  - Public knowledge and attitudes toward epilepsy in Majmaah.
AB  - OBJECTIVES: Epilepsy is very common in the Kingdom of Saudi Arabia, occurring in
      6.54 out of every 1000 individuals. The current study was conducted to determine
      the level of public awareness of and attitudes toward epilepsy in the city of
      Majmaah, Saudi Arabia. SUBJECTS AND METHODS: This descriptive study was conducted
      in Majmaah, Saudi Arabia. The study population included respondents derived from
      preselected public places in the city. Stratified random sampling was used, and
      the sample size was made up of 706 individuals. A structured questionnaire was
      used for data collection from respondents after receiving their verbal consent.
      The data were analyzed using SPSS version 2.0. Ethical approval was obtained from
      the Ethics Committee of Majmaah University. RESULTS: The results showed that 575
      (81.4%) of the respondents had heard or read about epilepsy. Almost 50% of the
      respondents knew someone who had epilepsy, and 393 (55.7%) had witnessed what
      they believed to be a seizure. Results showed that 555 (78.6%) respondents
      believed that epilepsy was neither a contagious disease nor a type of insanity.
      It was found that 335 (47.5%) stated that epilepsy was a brain disease, and
      almost one-quarter of the respondents said that the manifestation of an epileptic
      episode is a convulsion. Regarding attitude, 49% and 47.3% of respondents stated
      that they would not allow their children to interact with individuals with
      epilepsy and would object to marrying an individual with epilepsy, respectively.
      CONCLUSION: Although knowledge about epilepsy is improving, it is still not
      adequate. The study showed that the attitude toward epilepsy is poor.

PMID- 27695228
TI  - Knowledge, attitude, and practice of stroke among high school students in Nepal.
AB  - BACKGROUND: Baseline stroke knowledge in a targeted population is indispensable
      to promote the effective stroke education. We report the baseline knowledge,
      attitude, and practice (KAP) of high school students with respect to stroke from
      Nepal. MATERIALS AND METHODS: A self-structured questionnaire survey regarding
      KAP about stroke was conducted in high school students of 33 schools of
      Bharatpur, Nepal. Descriptive statistics including Chi-square test was used, and
      the significant variables were subjected to binary logistic regression. RESULTS:
      Among 1360 participants, 71.1% had heard or read about stroke; 30.2% knew someone
      with stroke. 39.3% identified brain as the organ affected. Sudden onset limb/s
      weakness/numbness (72%) and hypertension (74%) were common warning symptom and
      risk factor identified. 88.9% would take stroke patients to a hospital. Almost
      half participants (55.5%) felt ayurvedic treatment be effective. 44.8% felt
      stroke as a hindrance to a happy life and 86.3% believed that family care was
      helpful for early recovery. Students who identified at least one risk factor were
      3.924 times (P < 0.001, confidence interval [CI] = 1.867-8.247) or those who
      identified at least one warning symptom were 2.833 times (P <= 0.023, CI = 1.156
      6.944) more likely to take stroke patients to a hospital. CONCLUSION: KAP of high
      school Nepalese students regarding stroke was satisfactory, and the students
      having knowledge about the risk factors and warning symptoms were more likely to
      take stroke patients to a hospital. However, a few misconceptions persisted.

PMID- 27695229
TI  - Ki-67 immunostaining in astrocytomas: Association with histopathological grade -
      A South Indian study.
AB  - BACKGROUND: Astrocytomas are the most common primary tumor of the central nervous
      system. The distinction between different tumor grades can be tested despite
      criteria given by the World Health Organization (WHO). Ki-67 is a potent
      biological marker used in grading of astrocytomas, which estimates growth of the
      neoplasm quantitatively and will help in predicting prognosis accurately.
      OBJECTIVES: The aim of this was to study the proliferative activity using Ki-67
      immunostaining and to assess the relationship of Ki-67 staining with the
      histopathological grading of astrocytomas. PATIENTS AND METHODS: Thirty cases of
      histologically proven astrocytomas were studied. The histopathological grade was
      assessed using the 2007 WHO criteria. Immunohistochemistry for Ki-67 was done on
      paraffin-embedded wax sections. P < 0.05 was considered statistically
      significant. RESULTS: Thirty cases of astrocytomas studied showed a male
      preponderance (M:F = 1.72:1) with a mean age of 48.1 years. Of these, Grade I, (n
      = 1, 3.33%), Grade II, (n = 7, 23.3%), Grade III (n = 6, 20%), and Grade IV (n =
      16, 53.3%) astrocytomas were analyzed. The mean Ki-67 labeling index (LI) in
      Grades I, II, III, and IV was 0.02, 0.81, 9.14, and 17.81, respectively.
      Statistically significant difference was seen in the Ki-67 LI of low-grade (Grade
      II) and high-grade astrocytomas (Grades III and IV). There was concordance
      between histopathological grading and Ki-67 LI in 27 (90%) and discordance in 3
      (10%) cases. CONCLUSION: Ki-67 LI varies considerably in different grades of
      astrocytomas and considerable overlaps can be observed between them. It can be of
      great help in situations where there is a lack of correlation between clinical
      parameters and histopathological diagnosis. Determination of Ki-67 LI should
      constitute a part of routine investigations in patients with astrocytomas.

PMID- 27695230
TI  - Epidemiology, clinical characteristics and outcomes of traumatic brain injury:
      Evidences from integrated level 1 trauma center in India.
AB  - INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of mortality,
      morbidity, disability, and socioeconomic losses in the Indian subcontinent.
      However, for policymaking and research, there is a lack of reliable and larger
      data in our settings. AIMS AND OBJECTIVES: To evaluate and describe the
      epidemiological, clinical characteristics, and outcomes of patients with TBI in a
      Level 1 Trauma Center in India. MATERIALS AND METHODS: In this retrospective
      study, all patients with moderate or severe TBI, based on emergency department
      Glasgow Coma Scale, admitted to neurosurgery Intensive Care Unit (ICU) during May
      2010-July 2012 were evaluated to provide detailed information on TBI-related
      variables and outcomes using descriptive statistics. RESULTS: Among the 1527
      patients with moderate or severe TBI patients with mean age 32.15 +/- 16.76 years
      (range: 1-90) and male:female ratio 6.5:1, 1281 (83.89%) had severe TBI. The
      majority of cases took place in the age group of 21-40 years (50.24%) with the
      most common mode of injury as road traffic accidents (RTAs) (64.96%). Surgical
      intervention (craniotomy) was done in 49.12% of patients. About 34.58% (n = 528)
      patients died in hospital, and 67.21% (n = 701) had unfavorable outcome at 6
      months. CONCLUSIONS: This is the first study of its kind from the Indian
      subcontinent that gives data on the admission characteristics, mortality, and 6
      months outcome of such patients. Most of the injuries occurred due to RTAs, more
      common among the economic productive age groups and mostly in males with a high
      rate of mortality and unfavorable outcome.

PMID- 27695231
TI  - Human epidermal growth factor receptor 2/neu protein expression in meningiomas:
      An immunohistochemical study.
AB  - BACKGROUND: Meningiomas are common slow-growing primary central nervous system
      tumors that arise from the meningothelial cells of the arachnoid and spinal cord.
      Human epidermal growth factor receptor 2 (HER2) or HER2/neu (also known as c
      erbB2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity
      expressed in meningiomas and various other tumors. It can be used in targeted
      therapy for HER2/neu positive meningiomas. AIM: To correlate the expression of
      HER2/neu protein in meningiomas with gender, location, histological subtypes, and
      grade. MATERIALS AND METHODS: It was 31/2 years prospective (March 2010-October
      2011) and retrospective (May 2008-February 2010) study of histopathologically
      diagnosed intracranial and intraspinal meningiomas. Clinical details of all the
      cases were noted from the computerized hospital information system.
      Immunohistochemistry for HER2/neu protein was performed along with scoring.
      Statistical analysis was done using Chi-square test to look for any association
      of HER2/neu with gender, location, grade, and various histological subtypes of
      meningiomas at 5% level of significance. RESULTS: A total of 100 cases of
      meningiomas were found during the study period. Of which, 80 were Grade I, 18
      were Grade II, and 2 were Grade III meningiomas as per the World Health
      Organization 2007 criteria. The female-male ratio was 1.9:1 and the mean age was
      47.8 years. HER2/neu protein was expressed in 75% of Grade I and 72.2% of Grade
      II and none of Grade III meningiomas. About 72.7% brain invasive meningiomas
      showed HER2/neu immunopositivity. CONCLUSION: HER2/neu protein was expressed in
      73% of meningiomas. Statistically significant difference of HER2/neu expression
      was not seen between females and males of Grade I and Grade II/III meningiomas,
      intracranial and spinal tumors, Grade I and Grade II/III cases, and various
      histological subtypes of meningiomas.

PMID- 27695232
TI  - Nummular headache: Clinico-epidemiological features in South Indian population.
AB  - CONTEXT: Nummular headache (NH) is a primary disorder characterized by head pain
      exclusively felt in a small-rounded area typically 2-6 cm in diameter. AIMS: The
      aim of this review is to study the clinical and epidemiological features of NH in
      a patient population of South India and to compare this with that of described in
      the international literature. SETTINGS AND DESIGN: A prospective, observational
      study conducted in a tertiary care center. MATERIALS AND METHODS: Patients
      attending the medicine and neurology outpatient departments of a tertiary
      referral hospital in South India diagnosed to have NH as per the International
      Classification of Headache Disorders 3 beta (2013) criteria were studied over 30
      months. All of the patients had a normal neurological examination. Neuroimaging
      findings were normal, except in one patient. RESULTS: A total of 19 females and
      10 males were studied. The mean age of onset was 47.62 years (range 36-60). The
      duration of headache varied from a minimum of 3 months to a maximum of 5 years,
      with a mean of 24.17 months. The site of headache was predominantly in the
      parietal area 15 (51.72%), followed by the occipital area 7 (24.13%). The mean
      diameter of the affected area was 3.23 cm. The intensity of the headache proved
      to be mild to moderate with a mean visual analog scale score of 5.03. The quality
      of pain was mainly felt as burning dysesthesia 12 (41.38%). In the majority of
      patients, i.e. 21 (72.41%), pain was chronic and continuous. None of the patients
      had any significant trophic change even though paresthesias, dysesthesias, and
      allodynia were reported by a significant minority of patients, i.e. 9 (31.03%).
      Only one (3.45%) patient gave a history of head injury. Ten (34.48%) out of 29
      patients had other types of concurrent headaches; the majority of which proved to
      be migrainous, i.e. 7 (24.14%), 2 patients (6.89%) with tension headache, and 1
      patient (3.45%) with trigeminal neuralgia. CONCLUSION: Our study proves the
      existence of the newly described primary headache syndrome called NH in South
      Indian population. In comparing our results with the international literature,
      the number of similarities is much greater than the differences. The etiology of
      pain in our series appeared to be primarily peripheral with a role for central
      pain sensitization in some cases due to a variety of concurrent central causes of
      head pain.

PMID- 27695233
TI  - Evaluation of pituitary function in cases with the diagnosis of pediatric mild
      traumatic brain injury: Cross-sectional study.
AB  - BACKGROUND: This study was to determine whether pituitary dysfunction occurs
      after head trauma in children or not and which axis is affected more; to define
      the association of pituitary dysfunction with the severity of head trauma and
      duration time after the diagnosis of head trauma. MATERIALS AND METHODS: In this
      study, 24 children who were diagnosed with head trauma were evaluated regarding
      pituitary dysfunction. In all cases, after 12 h fasting, serum cortisol, fT3,
      fT4, thyroid-stimulating hormone, prolactin, insulin-like growth factor-1, serum
      sodium, urine density, follicle-stimulating hormone, luteinizing hormone, in
      female cases E2, in male cases, TT levels were determined. RESULTS: Mean age of
      children was 9.5 +/- 3.1 years, 14 children (58.3%) had mild, 9 children (37.5%)
      had moderate, and 1 children (4.2%) had severe head trauma according to the
      Glasgow coma scale. Mean duration time after head trauma was 29.4 +/- 9.8 months.
      In all cases, no pathologic condition was determined in the pituitary hormonal
      axis. In one children (4.2%), low basal cortisol level was found. There were no
      children with hormonal deficiency in this study. CONCLUSION: Although pituitary
      dysfunction after head trauma may develop in the early period, some may present
      in the late period; therefore, all cases should be followed up at outpatient
      clinics for a longer period.

PMID- 27695235
TI  - Comparative analysis of pedicle screw versus hybrid instrumentation in adolescent
      idiopathic scoliosis surgery.
AB  - INTRODUCTION: Adolescent idiopathic scoliosis is the most common type of
      scoliosis. A Cobb angle of 50 degrees  will progress beyond the age of spinal
      maturity. Surgery over bracing is advised at a Cobb angle above or equal to 50
      degrees . The aim of surgery is to bring the Cobb angle down below 50 degrees  to
      prevent reprogression as well as improve the quality of life. The objective of
      the study is to analyze the efficacy and significance in lifestyle improvement of
      pedicle screw-only fixation system versus the more common hybrid instrumentation
      system used for the surgical treatment of adolescent idiopathic scoliosis.
      MATERIALS AND METHODS: A prospective cohort study was conducted involving two
      groups of patients were included in the study. One group was operated with
      pedicle screw-only method while the other with hybrid instrumentation system. The
      pre- and post-operative Cobb's angles were taken across a follow-up of 4 years.
      An SRS-30 questionnaire was given in a yearly follow-up to assess the lifestyle
      improvement of the patient. RESULTS: Pedicle screw-only method was significantly
      more effective in reducing Cobb's angle (P = 0.0487). It was showed less loss of
      correction (P = 0.009) pedicle screw-only surgery was also better at reducing
      thoracic curves (P = 0.001). There seemed a better recovery time with pedicle
      screw surgery (P = 0.003). CONCLUSION: Pedicle screws are more effective and
      durable than hybrid systems at when treating adolescent idiopathic scoliosis.

PMID- 27695234
TI  - Role of ankle foot orthosis in improving locomotion and functional recovery in
      patients with stroke: A prospective rehabilitation study.
AB  - OBJECTIVE: To study role of ankle foot orthosis (AFO) in improving locomotion and
      functional recovery after stroke. SETTING: Neurological Rehabilitation Department
      of a university research tertiary hospital. PATIENTS AND METHODS: AFO and
      activity based rehabilitation. MAIN OUTCOME MEASURES: Distance (meters) covered
      during the 6-minute walk test (6MWT) and speed (meter/second) during the 10-meter
      walk test. Functional abilities assessed using Functional Independence Measure
      (FIM(r)). RESULTS: Twenty-six patients (21 male) with stroke (mean duration 196.7
      days, range 45-360 days) and mean age of 41.6 years (range 18-65 years, standard
      deviation [SD] 12.5) were included. Fourteen had right hemiplegia. The mean
      length of stay in the unit was 26.5 days (range 18-45 days, SD 5.5). All patients
      had equinus deformity with spastic foot drop and were provided with AFO. Walking
      endurance with 6MWT was 90 m on admission (without AFO). At discharge, it
      improved to 174 m with AFO and 121 m without AFOs (P < 0.001-with and without AFO
      at discharge). Walking speed improved from 0.4 m/s (admission) to 0.51 m/s with
      AFO, P = 0.004 and 0.45 m/s without AFO, P = 0.015) at discharge. Nine patients
      (34.6%) had clinically important difference-minimal clinically important
      difference (>0.16 m/s speed gain; >50 m endurance gain) at discharge. The mean
      FIM(r) score on admission was 84.3 +/- 18.6. At discharge FIM(r) improved to
      101.9 +/- 13.7 (P < 0.001). CONCLUSIONS: Use of AFOs improve gait parameters
      significantly in only one-third stroke patients in the study when combined with
      activity-based inpatient-rehabilitation.

PMID- 27695236
TI  - Clinical features, risk factors, and outcome of cerebral venous thrombosis in
      Tehran, Iran.
AB  - INTRODUCTION: Despite increasing the use of magnetic resonance imaging (MRI),
      cerebral venous sinus thrombosis (CVST) has remained an under-diagnosed
      condition. In this study, characteristics and frequency of various risk factors
      of CVST patients in a tertiary referral hospital were closely assessed. METHODS:
      Patients with an unequivocal diagnosis of CVST confirmed by MRI and magnetic
      resonance venography during 6 years of the study were included. All data from the
      onset of symptoms regarding clinical signs and symptoms, hospital admission,
      seasonal distribution, medical and drug history, thrombophilic profile, D-dimer,
      neuroimaging, cerebrospinal fluid findings, mortality, and outcome were collected
      and closely analyzed. RESULT: A total of 53 patients with female to male ratio of
      3.07 and mean age of 33.7 years were included in the study. Headache and
      papilledema were the most frequent clinical features (44 and 36 patients,
      respectively). An underlying disease (diagnosed previously or after admission)
      was the most common identified risk factor for CVST in both females and males (21
      patients). A total of 15 women used the oral contraceptive pill (OCP) where 12 of
      them had simultaneously other predisposing factors. Overall, 19 patients (36%)
      had more than one contributing factor. D-dimer had a sensitivity of 71.4% in CVST
      patients. The mortality of patients in this study was 3.7% (n = 2). Focal
      neurologic deficit and multicranial nerve palsy were associated with poor outcome
      which defined as death, recurrence, and massive intracranial hemorrhage due to
      anticoagulation (P = 0.050 and 0.004, respectively). CONCLUSION: Unlike most of
      the CVST studies in which OCP was the main factor; in this study, an underlying
      disease was the most identified cause. Considering the high probability of
      multiple risk factors in CVST that was shown by this study, appropriate work up
      should be noted to uncover them.

PMID- 27695240
TI  - Morvan's syndrome with anti contactin associated protein like 2 - voltage gated
      potassium channel antibody presenting with syndrome of inappropriate antidiuretic
      hormone secretion.
AB  - Morvan's syndrome is a rare autoimmune disorder characterized by triad of
      peripheral nerve hyperexcitability, autonomic dysfunction, and central nervous
      system symptoms. Antibodies against contactin-associated protein-like 2 (CASPR2),
      a subtype of voltage-gated potassium channel (VGKC) complex, are found in a
      significant proportion of patients with Morvan's syndrome and are thought to play
      a key role in peripheral as well as central clinical manifestations. We report a
      patient of Morvan's syndrome with positive CASPR2-anti-VGKC antibody having
      syndrome of inappropriate antidiuretic hormone as a cause of persistent
      hyponatremia.

PMID- 27695239
TI  - Surgical resection of low-grade gliomas in eloquent areas with the guidance of
      the preoperative functional magnetic resonance imaging and craniometric points.
AB  - OBJECTIVES: Surgical resection of low-grade gliomas (LGGs) in eloquent areas is
      one of the challenges in neurosurgery, using assistant tools to facilitate
      effective excision with minimal postoperative neurological deficits has been
      previously discussed (awake craniotomy and intraoperative cortical stimulation);
      however, these tools could have their own limitations thus implementation of a
      simple and effective technique that can guide to safe excision is needed in many
      situations. MATERIALS AND METHODS: The authors conducted a retrospective analysis
      of a prospectively collected data of 76 consecutive surgical cases of LGGs of
      these 21 cases were situated in eloquent areas. Preoperative functional magnetic
      resonance imaging (fMRI), pre- and post-operative MRI with volumetric analysis of
      the tumor size was conducted, and intraoperative determination of the
      craniometric points related to the tumor (navigation guided in 10 cases) were
      studied to evaluate the effectiveness of the aforementioned tools in safe
      excision of the aforementioned tumors. RESULTS: Total-near total excision in 14
      (66.67%) subtotal in 6 (28.57%), and biopsy in 1 case (4.57%). In long-term
      follow-up, only one case experienced persistent dysphasia. CONCLUSION: In spite
      of its simplicity, the identification of the safe anatomical landmarks guided by
      the preoperative fMRI is a useful technique that serves in safe excision of LGGs
      in eloquent areas. Such technique can replace intraoperative evoked potentials or
      the awake craniotomy in most of the cases. However, navigation-guided excision
      might be crucial in deeply seated and large tumors to allow safe and radical
      excision.

PMID- 27695238
TI  - Duration of suicide process among suicide attempters and characteristics of those
      providing window of opportunity for intervention.
AB  - BACKGROUND: There is limited cross-cultural literature on the duration of suicide
      process among attempters. AIMS: The primary aim was to assess the duration of
      suicide process among suicide attempters attending the Crisis Intervention
      Clinic. We also aimed to identify the characteristics of those who reported a
      longer duration for this process. METHODS: In this retrospective record-based
      study, we collected the duration of the suicidal process from the records of all
      the suicide attempters evaluated over a 3-year period (n = 319). Attempters were
      divided into four groups based on the quartile value of the duration of the
      suicidal process. For analysis, the characteristics of those in the last quartile
      with suicide process time of >120 min (n = 75) were compared with those in the
      first three (n = 244). Those in the last quartile were considered to provide a
      window of opportunity for intervention. RESULTS: The median time for the suicidal
      process was 30 min (interquartile range of 5 min to 120 min). Seventy-five
      (23.5%) subjects belonged to the fourth quartile (duration of suicide process
      >120 min). A significant proportion of them came from urban areas (P = 0.011),
      had a diagnosis of mood disorder (P = 0.028), had visited a health professional
      in the recent past (P = 0.015), and had lower rates of attempt under intoxication
      (P = 0.005). A lesser proportion of them showed problem-focused disengagement
      style of coping strategy (P = 0.015). CONCLUSIONS: The suicide process time among
      Indian suicide attempters is short. However, a quarter of them has suicide
      process duration of 2 h which provides some scope for intervention. Individual
      and community level interventions need further evaluation for their potential
      efficacy in preventing the progress of the suicidal process.

PMID- 27695241
TI  - Commentary.

PMID- 27695237
TI  - Determining rural risk for aneurysmal subarachnoid hemorrhages: A structural
      equation modeling approach.
AB  - An aneurysmal subarachnoid hemorrhage (aSAH) carries a high disability burden.
      The true impact of rurality as a predictor of outcome severity is unknown. Our
      aim is to clarify the relationship between the proposed explanations of regional
      and rural health disparities linked to severity of outcome following an aSAH. An
      initial literature search identified limited data directly linking geographical
      location, rurality, rural vulnerability, and aSAH. A further search noting
      parallels with ischemic stroke and acute myocardial infarct literature presented
      a number of diverse and interrelated predictors. This a priori knowledge informed
      the development of a conceptual framework that proposes the relationship between
      rurality and severity of outcome following an aSAH utilizing structural equation
      modeling. The presented conceptual framework explores a number of system,
      environmental, and modifiable risk factors. Socioeconomic characteristics,
      modifiable risk factors, and timely treatment that were identified as predictors
      of severity of outcome following an aSAH and within each of these defined
      predictors a number of contributing specific individual predictors are proposed.
      There are considerable gaps in the current knowledge pertaining to the impact of
      rurality on the severity of outcome following an aSAH. Absent from the literature
      is any investigation of the cumulative impact and multiplicity of risk factors
      associated with rurality. The proposed conceptual framework hypothesizes a number
      of relationships between both individual level and system level predictors,
      acknowledging that intervening predictors may mediate the effect of one variable
      on another.

PMID- 27695242
TI  - Cystic dilation of the ventriculus terminalis.
AB  - The ventriculus terminalis (VT) is a virtual cavity of the conus medullaris that
      appears during embryonic life. We presented a case with the cystic dilation of
      the ventriculus terminalis (CDVT) in a symptomatic patient. A 66-year-old female
      suffered from disturbance while walking evolving for the past 2 years. An MR
      image revealed a cystic dilatation of ventriculus terminalis. The patient
      experienced marked improvement of lower extremity strength by a fenestration of
      cyst and cyst-subarachnoid shunt. Treatment for asymptomatic patients seems to be
      the best conducted conservatively, whereas patients with focal neurological
      deficits seem to be best handled surgically.

PMID- 27695243
TI  - Writer's cramp in spinocerebellar ataxia Type 1.
AB  - Dystonia can be encountered in a small subset of patients with spinocerebellar
      ataxia (SCA), but task specific dystonia is extremely rare. We report a case of a
      48-year-old male with confirmed SCA Type 1 (SCA1) with mild progressive
      cerebellar ataxia and a prominent and disabling Writer's cramp. This case
      highlights the ever-expanding phenotypic heterogeneity of the SCA's in general
      and SCA1 in particular.

PMID- 27695244
TI  - Cardiac arrhythmia in Wilson's disease: An oversighted and overlooked entity!
AB  - Wilson's disease is a multisystem disorder which manifests with hepatic,
      neurological, musculoskeletal, hematological, renal, and cardiac symptoms. The
      hepatic and neurological manifestations often overshadow the other system
      involvement including cardiac symptoms and signs, which may prove fatal. We
      report a case of a young female who presented with progressive parkinsonian
      features and dystonia for around 4 months followed 2 months later by the
      complaint of episodes of light-headedness. She was diagnosed to have Wilson's
      disease based on the presence of Kayser-Fleischer ring and laboratory parameters
      of copper metabolism. Electrocardiography of the patient incidentally revealed
      2nd degree Mobitz type-1 atrioventricular block explaining her episodes of light
      headedness. She was started on penicillamine and trihexyphenidyl. The heart block
      improved spontaneously. Cardiac autonomic function tests including blood pressure
      response to standing and heart rate response to standing were observed to be
      normal. We review the literature on cardiac manifestations of Wilson's disease
      and emphasize that patients with Wilson's disease should be assessed for cardiac
      arrhythmia and cardiac dysfunction as these may have therapeutic and prognostic
      implications.

PMID- 27695245
TI  - Commentary.

PMID- 27695247
TI  - Unilateral spontaneous ankylosis of the C1/C2 joint with "crowned dens syndrome":
      Computed tomography scan is imperative in diagnosis.

PMID- 27695246
TI  - Meningitis with polymerase chain reaction for varicella zoster positivity in
      cerebrospinal flid of a young immunocompetent adult.
AB  - Meningitis caused by varicella zoster virus (VZV) is quite rare among young
      immunocompetent adults though immunocompromised patients are often seen to be
      affected by reactivation of VZV presenting with primary clinical features of
      dermatomal rashes and neurological sequelae. Here, we report the clinical
      scenario of a young, healthy male who had presented with fever, headache, and
      onset of dermatomal rashes later than the fever and was eventually diagnosed to
      be a case of VZV meningitis. We would like to highlight the fact that even young
      immunocompetent patients though rarely, might contract VZV meningitis and
      clinicians should have a high index of suspicion and keen eyes to catch the more
      obvious features of VZV infection on complete physical examination and must not
      harbor any reservations in ordering polymerase chain reaction for VZV DNA or
      initiating aggressive antiviral therapy.

PMID- 27695248
TI  - Mobius syndrome.

PMID- 27695250
TI  - Primary cerebral hydatid cyst: An unusual cause of very slowly progressive
      hemiparesis in a child.

PMID- 27695249
TI  - The use of intraoperative computed tomography navigation in pituitary surgery
      promises a better intraoperative orientation in special cases.
AB  - OBJECTIVE: The safety of endoscopic skull base surgery can be enhanced by
      accurate navigation in preoperative computed tomography (CT) and magnetic
      resonance imaging (MRI). Here, we report our initial experience of real-time
      intraoperative CT-guided navigation surgery for pituitary tumors in childhood.
      MATERIALS AND METHODS: We report the case of a 15-year-old girl with a huge
      growth hormone-secreting pituitary adenoma with supra- and perisellar extension.
      Furthermore, the skull base was infiltrated. In this case, we performed an
      endonasal transsphenoidal approach for debulking the adenoma and for chiasma
      decompression. We used an MRI neuronavigation (Medtronic Stealth Air System)
      which was registered via intraoperative CT scan (Siemens CT Somatom). Preexisting
      MRI studies (navigation protocol) were fused with the intraoperative CT scans to
      enable three-dimensional navigation based on MR and CT imaging data.
      Intraoperatively, we did a further CT scan for resection control. RESULTS: The
      intraoperative accuracy of the neuronavigation was excellent. There was an
      adjustment of <1 mm. The navigation was very helpful for orientation on the
      destroyed skull base in the sphenoid sinus. After opening the sellar region and
      tumor debulking, we did a CT scan for resection control because the extent of
      resection was not credible evaluable in this huge infiltrating adenoma. Thereby,
      we were able to demonstrate a sufficient decompression of the chiasma and
      complete resection of the medial part of the adenoma in the intraoperative CT
      images. CONCLUSIONS: The use of intraoperative CT/MRI-guided neuronavigation for
      transsphenoidal surgery is a time-effective, safe, and technically beneficial
      technique for special cases.

PMID- 27695252
TI  - Atypical antipsychotics for the treatment of musical hallucinations in an elderly
      patient without a psychiatric disorder.

PMID- 27695251
TI  - Iatrogenic dural arteriovenous fistula after surgical resection of a ruptured
      brain arteriovenous malformation.

PMID- 27695253
TI  - Epidural cerebrospinal fluid leak: A rare cause of upper limb amyotrophy - A
      report of two cases.

PMID- 27695254
TI  - Hypertension, headache, and posterior reversible encephalopathy syndrome.

PMID- 27695255
TI  - QT dispersion and acute cerebrovascular accident.

PMID- 27695257
TI  - Extra-axial dural cavernous hemangioma with dural tail sign, masquerading as
      meningioma.

PMID- 27695256
TI  - Future in neuromedicine: Nanotechnology.

PMID- 27695258
TI  - In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia
      glauca Stem Methanol Extract.
AB  - BACKGROUND: Galphimia glauca is an evergreen shrub found across peninsular India,
      belonging to family Malpighiaceae. OBJECTIVE: The objective of this study was to
      assess the in vivo depressant effects and muscle coordination activity of G.
      glauca stem methanol extract (GGSME). MATERIALS AND METHODS: The stem methanol
      extract was administered in Swiss albino mice in 1 day to study the central
      nervous system (CNS) depressant and muscle coordination activity employing animal
      models such as sodium pentobarbital-induced sleep test, hole-board test, open
      field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced
      convulsions, grip strengthening test in mice, and Rota-rod test. RESULTS: The
      LD50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with
      stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the
      sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem
      methanol extract at 400 mg/kg dose showed a significant (P <= 0.001) dose
      dependent decrease in the number of rears and head dipping number in the hole
      board test. The extract exhibited a significant (P <= 0.001) effect on the
      ambulatory behavior of mice in the open field test and also extended the onset of
      seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w.,
      i.p.). The extract also exhibited significant (P <= 0.001) effects on muscle
      coordination in rota-rod and grip strengthening test in mice. CONCLUSION: The
      study results conclude that the GGSME has a potential CNS depressant and muscle
      relaxant effects compared to the standard drugs. SUMMARY: Anxiety is implicated
      in the number of psychiatric disordersIn vivo depressant activity is studied
      employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board
      test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin
      induced convulsions tests.Muscle coordination activity is studied employing
      animal models like Grip strengthening test in mice and Rota-.rod test.The
      GABAergic system plays a significant role in CNS depressant and muscle relaxant
      effects.The study proves the traditional claims of the plant used in the
      treatment of phobia, panic, stress, anxiety and it is as well used in producing a
      calming effect on the nerves. Abbreviations Used: WHO: World Health Organization;
      CNS: Central nervous system; GGSME: Galphimia glauca stem methanol extract; IAEC:
      Institutional Animal Ethics Committee; OECD: The Organization for Economic Co
      operation and Development; PTZ: Pentylenetetrazole; REM: Rapid eye movement;
      GABA: gamma-aminobutyric acid; AMPA: alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor; b.w: Body weight; i.p: Intraperitoneal; p.o:
      per oral.

PMID- 27695259
TI  - Evaluation of Antiulcer and Antioxidant Activity of Barleria gibsoniDalz. Leaves.
AB  - BACKGROUND: Peptic ulcer is a digestive disorder most commonly found in clinical
      practice. Given the many side effects of modern medicine, the initial acquisition
      of fewer side effects, and medication of indigenous drugs, it should be
      considered as a better alternative for the treatment of peptic ulcer. OBJECTIVE:
      To assess antiulcer and antioxidant activity of ethanol extract of Barleria
      gibsoni (EBG) Dalz. leaves in ulcer-induced rats and in vitro antioxidants
      method, respectively. MATERIALS AND METHODS: Ethanol EBG was screened for
      antiulcer activity in pylorus ligation-induced ulcer models in Wistar rats. In
      vitro antioxidant activity of the extracts was tested using 2,2-diphenyl-1
      picrylhydrazyl (DPPH), nitric oxide (NO) radical scavenging activity. Total
      phenol and flavonoid content in the extracts were determined
      spectrophotometrically. RESULTS: Oral administration of ethanol extract of leaves
      at doses of 250, 500 mg/kg p.o. reduced significant gastric lesions induced by
      pylorus ligation-induced ulcer as compared to standard omeprazole (20 mg/kg
      p.o.). The IC50 values were found to be 150 MUg/mL in leaves extract. The ethanol
      extracts showed good antioxidant capacity in DPPH radical scavenging assay and NO
      radical scavenging activity when compared to standard. The total phenolic content
      using Folin-Ciocalteu reagent estimated in 1 mg of leaves extracts was 368 MUg
      and 481 MUg with gallic acid equivalent and also the total flavonoid content
      found to be 240 and 410 MUg, respectively, with quercetin equivalence.
      CONCLUSION: These findings suggest that the leaves of B. gibsoni possessed
      antiulcer potential and antioxidant compared to standard. This is the first ever
      report of antiulcer and antioxidant activities in B. gibsoni (Acanthaceae).
      SUMMARY: In vivo antiulcer and in vitro antioxidant activity of Barleria gibsoni
      was evaluated.Soxhelt extraction was carried out and extracts were subjected to
      qualitative phytochemical analysis. Extract obtained by Soxhlation showed higher
      total phenolic and flavonoid contents.EBG showed DPPH and Nitric oxide scavenging
      activity indicating its strong antioxidant potential.On pylorus ligation
      accumulated secretions and the related ulcers confirm gastric acid output to be
      the basic cause of gastric ulcers. Ethanol extract of leaves attenuated the
      gastric volume, free acidity, total acidity and ulcer index thus showing the anti
      secretory mechanism.The results of the histopathological investigation of
      Barleria gibsoni leaves for antiulcer effects using pylorus ligation induced
      ulcer model in rats laid credence to traditional use of the plant leaves in ulcer
      treatment. The ethanol extract of leaves demonstrated increase in percentage
      preventive index compared to omeprazole respectively. From the present study
      results reveals the antiulcer activity of ethanol extract leaves which is
      comparable to that of Omeprazole. Abbreviations Used: EBG: Ethanol extract
      prepared from the leaves of B. gibsoni, ROS: Reactive Oxygen Species, DPPH: 2, 2
      diphenyl-1-picrylhydrazyl, NO: Nitric Oxide, IC50: The half maximal inhibitory
      concentration, m: mg, DNA: deoxyribonucleic acid, GAE: Gallic acid equivalence,
      AlCl3: Aluminium chloride.

PMID- 27695260
TI  - Probing Regenerative Potential of Moringa oleifera Aqueous Extracts Using In
      vitro Cellular Assays.
AB  - BACKGROUND: Molecules stimulating regeneration and proliferation of cells are of
      significance in combating ailments caused due to tissue injury, inflammation, and
      degenerative disorders. Moringa oleifera is one of the most valued food plants
      having the profile of important nutrients and impressive range of medicinal uses.
      OBJECTIVE: To evaluate the potential of M. oleifera aqueous leaf and flower
      extracts to promote the proliferation of cells and explore their effect on cancer
      cell lines for assessment of safety. MATERIALS AND METHODS: Aqueous leaf and
      flower extracts of M. oleifera were investigated for effect on rat-derived
      primary fibroblast, mesenchymal stem cells (MSCs), and cancer cell lines using
      cell proliferation assay. They were also tested and compared for wound healing,
      angiogenesis, and hepatoprotective effect using in vitro assays. RESULTS:
      Statistically significant increase in the proliferation of primary rat
      fibroblast, MSCs, and angiogenesis was observed after treatment with aqueous
      flower extract. The aqueous leaf extract determined a comparatively moderate
      increment in the proliferation of MSCs and angiogenesis. It however showed
      prominent cytotoxicity to cancer cell lines and a significant hepatoprotective
      effect. CONCLUSION: A very clear difference in response of the two extracts to
      different types of cells was detected in this study. The aqueous flower extract
      exhibited a higher potential to stimulate cell proliferation while not exerting
      the same effect on cancer cell lines. The leaf extract on the other hand, had a
      prominent antitumor and hepatoptotective effects. SUMMARY: Moringa oleifera
      flower extract showed significant ability to promote proliferation of rat
      fibroblast and mesenchymal stem cells. The extract also had prominent angiogenic
      and hepatoprotective effects.The extract did not influence proliferation of
      cancer cell lines indicating its safety for human consumption and use in
      pharmaceuticals.The Moringa oleifera leaf extract showed relatively less
      potential to stimulate cells but had prominent cytotoxic effect on cancer cell
      lines. Abbreviations Used: ALT: Alanine transaminase, AST: Asparatate amino
      transferase, ATCC: American type culture collection, BMMSC: Bone marrow
      mesenchymal stem cells (used in this paper), CAM: Chick chorioallantoic membrane,
      CCl4: Carbon tetra chloride, DMEM: Dulbecco's modified Eagle medium, DMSO:
      Dimethyl sulfoxide, EDTA: Ethylene diamine tetraacetic acid, HBL 100: Human
      breast epithelial cell line, Mcf-7: Human breast adenocarcinoma cell line, aMEM:
      Minimum Essential Medium Eagle alpha modification, MOF: Moringa oleifera aqueous
      flower extract (used in this paper), MOL: Moringa oleifera aqueos leaf extract
      (Used in this paper), OD: Optical density, PBS: Phosphate buffered saline.

PMID- 27695261
TI  - High-performance Thin-layer Chromatography Method Development, Validation, and
      Simultaneous Quantification of Four Compounds Identified in Standardized Extracts
      of Orthosiphon stamineus.
AB  - CONTEXT: Orthosiphon stamineus is a medicinal herb widely grown in Southeast Asia
      and tropical countries. It has been used traditionally as a diuretic, abdominal
      pain, kidney and bladder inflammation, gout, and hypertension. AIMS: This study
      aims to develop and validate the high-performance thin layer chromatography
      (HPTLC) method for quantification of rosmarinic acid (RA), 3'-hydroxy-5,6,7,4'
      tetramethoxyflavone (TMF), sinensitin (SIN) and eupatorin (EUP) found in ethanol,
      50% ethanol and water extract of O. stamineus leaves. MATERIALS AND METHODS:
      HPTLC method was conducted using an HPTLC system with a developed mobile phase
      system of toluene: ethyl acetate: formic acid (3:7:0.1) performed on precoated
      silica gel 60 F254 TLC plates. The method was validated based on linearity,
      accuracy, precision, limit of detection, limit of quantification (LOQ), and
      specificity, respectively. The detection of spots was observed at ultraviolet 254
      nm and 366 nm. RESULTS: The linearity of RA, TMF, SIN, and EUP were obtained
      between 10 and 100 ng/spot with high correlation coefficient value (R2) of more
      than 0.986. The limit of detection was found to be 122.47 +/- 3.95 (RA), 43.38 +/
      0.79 (SIN), 17.26 +/- 1.16 (TMF), and 46.80 +/- 1.33 ng/spot (EUP),
      respectively. Whereas the LOQ was found to be 376.44 +/- 6.70 (RA), 131.45 +/-
      2.39 (SIN), 52.30 +/- 2.01 (TMF), and 141.82 +/- 1.58 ng/spot (EUP),
      respectively. CONCLUSION: The proposed method showed good linearity, precision,
      accuracy, and high sensitivity. Hence, it may be applied in a routine
      quantification of RA, SIN, TMF, and EUP found in ethanol, 50% of ethanol and
      water extract of O. stamineus leaves. SUMMARY: HPTLC method provides rapid
      estimation of the marker compound for routine quality control analysis.The
      established HPTLC method is rapid for qualitative and quantitative fingerprinting
      of Orthosiphon stamineus extract used for commercial product.Four identified
      markers (RA, SIN, EUP and TMF) found in three a different type of O. stamineus
      extracts specifically ethanol, 50% ethanol and water extract were successfully
      quantified using HPTLC method. Abbreviations Used: HPTLC: High-performance thin
      layer chromatography; RA: Rosmarinic acid; TMF: 3'-hydroxy-5,6,7,4'
      tetramethoxyflavone; SIN: Sinensitin; EUP: Eupatorin; E: Ethanol; EW: 50%
      ethanol; W: Water; BK: Batu Kurau; KB: Kepala Batas; S: Sik; CJ: Changkat Jering;
      SB: Sungai Buloh.

PMID- 27695262
TI  - Kayeassamin A Isolated from the Flower of Mammea siamensis Triggers Apoptosis by
      Activating Caspase-3/-8 in HL-60 Human Leukemia Cells.
AB  - BACKGROUND: Mammea siamensis (Miq.) T. Anders. is used as a medicinal plant in
      Thailand and has several traditional therapeutic properties. In a previous study,
      we isolated eight compounds from the flower of M. siamensis and demonstrated that
      kayeassamin A (KA) exhibited potent antiproliferative activity against human
      leukemia and stomach cancer cell lines. OBJECTIVE: In this study, we investigated
      the effect of KA on cell viability and apoptotic mechanisms in HL-60 human
      leukemia cells. MATERIALS AND METHODS: Cell viability was measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Nuclear morphology
      and DNA fragmentation were observed using Hoechst 33258 staining and agarose gel
      electrophoresis, respectively. The sub-G1 phase of cells was analyzed by flow
      cytometry after the cellular DNA had been stained with propidium iodide. The
      protein levels of poly (ADP-ribose) polymerase (PARP) and caspases were
      determined by Western blotting. RESULTS: KA exhibited a significant cytotoxic
      effect in a dose- and time-dependent manner, and induced chromatin condensation,
      DNA fragmentation, and sub-G1 phase DNA content, known as molecular events
      associated with the induction of apoptosis. In addition, KA strongly induced the
      activation of PARP and caspase-3 and -8, with weak caspase-9 activation.
      Furthermore, KA-induced DNA fragmentation was abolished by pretreatment with z
      VAD-FMK (a broad caspase inhibitor), z-DEVD-FMK (a caspase-3 inhibitor), and z
      IETD-FMK (a caspase-8 inhibitor), but not by z-LEHD-FMK (a caspase-9 inhibitor)
      pretreatment. CONCLUSION: These results indicate that KA triggers apoptotic cell
      death by activation of caspase-3 and -8 in HL-60 cells. SUMMARY: Kayeassamin A
      (KA) isolated from the flower of Mammea siamensis exhibited a significant
      cytotoxic effect in HL-60 human leukemia cells. KA triggers apoptotic cell death
      by activating caspase-3/-8. Abbreviations Used: KA: Kayeassamin A; MTT: 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PARP: Poly (ADP-ribose)
      polymerase; PI: Propidium iodide; CA: Corosolic acid.

PMID- 27695263
TI  - Effect of Musa sapientum Stem Extract on Animal Models of Depression.
AB  - BACKGROUND: Musa sapientum, the banana plant, has shown to possess antioxidant
      activity in previous studies. Oxidative stress has been linked to the
      pathogenesis of major depressive disorder (MDD) with evidence of increased serum
      levels of oxidative stress biomarkers in MDD patients. OBJECTIVE: The present
      study aimed to evaluate the antidepressant activity of M. sapientum stem extract
      (MSSE) in experimental models in mice. MATERIALS AND METHODS: Forced swim test
      (FST) and tail suspension test (TST) were carried out in five different groups (n
      = 6/group) of mice. The vehicle, standard drug, and the three test groups were
      orally administered distilled water (10 mL/kg), fluoxetine (25 mg/kg), and
      incremental doses of 25, 50, and 100 mg of MSSE, respectively, 45 min prior to
      the experiment. RESULTS: On FST, the duration of immobility in control group,
      which was 161.5 +/- 6.78 (in seconds, mean +/- standard error of mean [SEM]),
      decreased to 149.33 +/- 2.70 (25 mg/kg MSSE), 120.17 +/- 8.35 (50 mg/kg MSSE),
      and 45.17 +/- 4.11 (100 mg/kg MSSE) in the treated groups. On TST, the duration
      of immobility in control group, which was 173.83 +/- 12.65 (mean +/- SEM),
      decreased to 163.17 +/- 6.91 (25 mg/kg MSSE), 139.0 +/- 5.9 (50 mg/kg MSSE), and
      124.0 +/- 4.42 (100 mg/kg MSSE) in the treated groups. The difference in the
      duration of immobility was statistically significant at middle and higher doses,
      i.e. 50 and 100 mg/kg MSSE (P < 0.05) respectively, when compared with the
      control group in both the tests. CONCLUSION: A significant antidepressant-like
      activity was found in MSSE, which could be a potential natural compound for use
      in depression. SUMMARY: The five groups - vehicle, standard drug, and the three
      test groups were administered distilled water (10 mL/kg), fluoxetine (25 mg/kg),
      and incremental doses of 25, 50, and 100 mg of Musa sapientum stem extract
      (MSSE), respectivelyThe duration of immobility decreased in the treated groups as
      compared to the control group on both, forced swim and tail suspension, testsThe
      difference in the duration of immobility was statistically significant at middle
      and higher doses, i.e., 50 and 100 mg/kg MSSE (P < 0.05), when compared with the
      control group in both the tests. Abbreviations Used: MDD: Major depressive
      disorder; MSSE: Musa sapientum stem extract; FST: Forced swim test; TST: Tail
      suspension test; GSH: Glutathione, MDA: Malondialdehyde; SOD: Superoxide
      dismutase.

PMID- 27695264
TI  - Chemical Characterization and Cytoprotective Effect of the Hydroethanol Extract
      from Annona coriacea Mart. (Araticum).
AB  - INTRODUCTION: Annona coriacea Mart. (araticum) is a widely distributed tree in
      the cerrado. Its value is attributed principally to the consumption of its fruit
      which possesses a large nutritive potential. The objective was to identify the
      chemical profile and evaluate the antimicrobial and cytoprotective activity of
      the hydroethanol extract of A. coriacea Mart. (HEAC) leaves against the toxicity
      of mercury chloride. MATERIALS AND METHODS: The characterization of components
      was carried out using high-performance liquid chromatography (HPLC). The minimum
      inhibitory concentration (MIC) was determined by microdilution method in broth
      with strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas
      aeruginosa. For evaluation of the modulatory and cytoprotective activity of
      aminoglycoside antibiotics (gentamicin and amikacin) and mercury chloride
      (HgCl2), the substances were associated with the HEAC at subinhibitory
      concentrations (MIC/8). RESULTS AND DISCUSSION: The HPLC analysis revealed the
      presence of flavonoids such as Luteolin (1.84%) and Quercetin (1.19%) in elevated
      concentrations. The HEAC presented an MIC >=512 MUg/mL and significant
      antagonistic action in aminoglycosides modulation, and it also showed
      cytoprotective activity to S. aureus (significance P < 0.0001) and E. coli
      (significance P < 0.05) bacteria against the mercury chloride heavy metal with
      significance, this action being attributed to the chelating properties of the
      flavonoids found in the chemical identification. CONCLUSIONS: The results
      acquired in this study show that the HEAC presents cytoprotective activity over
      the tested strains in vitro and can also present antagonistic effect when
      associated with aminoglycosides, reinforcing the necessity of taking caution when
      combining natural and pharmaceutical products. SUMMARY: The hydroalcoholic
      extract of A. coriacea Mart. presents in vitro cytoprotective activity against
      the toxic effect of Hg. Abbreviations Used: HPLC-DAD: High-performance liquid
      chromatography with a diode array detector; MIC: Minimum inhibitory
      concentration; DMSO: Dimethyl sulfoxide.

PMID- 27695265
TI  - In vitro Antioxidant Activities and Polyphenol Contents of Seven Commercially
      Available Fruits.
AB  - BACKGROUND: Fruits are considered one of the richest sources of natural
      antioxidants. Their consumption has been linked to the prevention of oxidative
      stress-induced diseases. OBJECTIVE: In this study, in vitro antioxidant
      activities of blueberry, jackfruit, blackberry, black raspberry, red raspberry,
      strawberry, and California table grape extracts were evaluated. MATERIALS AND
      METHODS: Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl
      (DPPH), ferric reducing antioxidant potential (FRAP), 2,2'-azino-bis (3
      ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), nitric oxide (NO),
      superoxide anion (O2-) scavenging assays, and ferric reducing power. RESULTS:
      Black raspberry extract had the highest phenolic (965.6 +/- 2.9 mg gallic acid
      equivalents [GAE]/g), flavonoid (186.4 +/- 1.7 mg quercetin equivalents/g), and
      proanthocyanidin (2677 +/- 71.1 mg GAE/g) contents. All fruit extracts exhibited
      increasing radical scavenging activities with increased concentrations. At 100
      MUg/ml, red raspberry extract showed the highest ferric reducing power (A700 =0.3
      +/- 0.0052) and FRAP activity (A593 =11.43 mM Fe2+/g). Black raspberry extract
      (100 MUg/ml) exhibited the highest DPPH activity (A517 =89.03 +/- 0.0471).
      Jackfruit extract (100 MUg/ml) had the highest ABTS (A734 =35.6 +/- 0.613), NO
      (A540 =81.7 +/- 0.2), and O2- radical scavenging (A230 =55.5 +/- 0.2) activities.
      Positive correlations were observed between IC50 values for different radical
      scavenging activities and different polyphenolics. Red raspberry extract had the
      highest Pearson's coefficient values (0.952-1) between total phenolics,
      flavonoids, and proanthocyanidins and DPPH and superoxide radical scavenging
      activities. CONCLUSIONS: The antioxidant rich fruits in this study are good
      source of functional food and nutraceuticals that have the potential to improve
      human health. SUMMARY: All fruit extracts exhibited increasing radical scavenging
      activities with increased concentrationsBlack raspberry extract is enriched in
      total phenols, flavonoids, and proanthocyanidins and showed the highest 2,2
      diphenyl-1-picrylhydrazyl scavenging activity and red raspberry extract showed
      the highest ferric reducing power and ferric reducing antioxidant potential
      activityJackfruit extract exhibited the highest 2,2'azino-bis (3
      ethylbenzothiazoline-6-sulfonicacid) diammonium salt, nitric oxide, O2-
      scavenging activitiesPositive correlations were observed between IC50 values for
      different radical scavenging activities and different polyphenolics.
      Abbreviations Used: Abs: Absorbance, ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline
      6-sulfonic acid) diammonium salt, BHT: Butylated hydroxytoluene, DPPH: 2,2
      diphenyl-1-picrylhydrazyl, DW: Dry weight, FRAP: Ferric reducing antioxidant
      potential, FW: Fresh weight, GAE: Gallic acid equivalents, NADH: beta
      nicotinamide adenine dinucleotide hydrate, NFL: The National Food Laboratories,
      NO: Nitric oxide, ONPG: ortho-nitrophenyl-beta-galactoside, PBS: Phosphate
      buffered saline, PMS: Phenazine methosulfate, QE: Quercetin equivalents, ROS:
      Reactive oxygen species, SD: Standard deviation, SOD: Superoxide dismutase, TCA:
      Trichloroacetic acid, TPTZ: 2,4,6-tris(2-pyridyl)-s-triazine, Trolox: (+/-)-6
      hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid.

PMID- 27695266
TI  - Evaluation of In vitro Antiviral Activity of Datura metel Linn. Against Rabies
      Virus.
AB  - OBJECTIVE: The soxhlet and cold extracts of Datura metel Linn. were evaluated for
      in vitro antirabies activity. MATERIALS AND METHODS: Soxhlet and cold extraction
      method were used to extract Datura (fruit and seed) extracts. In vitro
      cytotoxicity assay was performed by 3-(4,5-dimethylthiazolyl-2)-2,5
      diphenyltetrazolium bromide assay. Based on the CC50 range, the in vitro
      antirabies activity of the extracts was screened by rapid fluorescent focus
      inhibition test and molecular method. RESULTS: The Datura (fruit and seed)
      extracts were not cytotoxic below 5 mg/ml (CC50). Titer of 10-4 rabies virus
      challenge virus standard (RV CVS) (1 50% tissue culture infective dose [1
      TCID50]) was obtained by RFFT method and the challenge dose of 10 TCID50 was used
      for antirabies assay. Datura fruit and seed (soxhlet and cold) extracts showed
      50% inhibition of RV CVS at 2.5 mg/ml and 1.25 mg/ml (inhibitory concentration
      50% [IC50]), respectively. The tested extracts showed selectivity index
      (CC50/IC50) ranging from 2 to 4. The viral RNA was extracted and real-time
      reverse transcription-polymerase chain reaction was performed which also revealed
      a 2-fold reduction of viral load at 1.25 mg/ml of the Datura seed (soxhlet
      methanolic and cold aqueous) extracts. CONCLUSION: To the best of our knowledge,
      this is the first study of in vitro antiviral activity of D. metel Linn. against
      rabies virus. Datura seed extracts have a potential in vitro antirabies activity
      and, in future, can be further screened for in vivo activity against rabies virus
      in murine model. SUMMARY: In the present study, Datura metel. Linn showed and in
      vitro anti rabies activity in Vero cell line which was determined by RFFIT method
      and PCR method.

PMID- 27695267
TI  - Influence of the Extractive Method on the Recovery of Phenolic Compounds in
      Different Parts of Hymenaea martiana Hayne.
AB  - BACKGROUND: Popularly known as "jatoba," Hymenaea martiana Hayne is a medicinal
      plant widely used in the Brazilian Northeast for the treatment of various
      diseases. OBJECTIVE: The aim of this study was to evaluate the influence of
      different extractive methods in the production of phenolic compounds from
      different parts of H. martiana. MATERIALS AND METHODS: The leaves, bark, fruits,
      and seeds were dried, pulverized, and submitted to maceration, ultrasound, and
      percolation extractive methods, which were evaluated for yield, visual aspects,
      qualitative phytochemical screening, phenolic compound content, and total
      flavonoids. RESULTS: The highest results of yield were obtained from the
      maceration of the leaves, which may be related to the contact time between the
      plant drug and solvent. The visual aspects of the extracts presented some
      differences between the extractive methods. The phytochemical screening showed
      consistent data with other studies of the genus. Both the vegetal part as the
      different extractive methods influenced significantly the levels of phenolic
      compounds, and the highest content was found in the maceration of the barks, even
      more than the content found previously. No differences between the levels of
      total flavonoids were significant. The highest concentration of total flavonoids
      was found in the ultrasound of the barks, followed by maceration on this drug.
      According to the results, the barks of H. martiana presented the highest total
      flavonoid contents. CONCLUSION: The results demonstrate that both the vegetable
      and the different extractive methods influenced significantly various parameters
      obtained in the various extracts, demonstrating the importance of systematic
      comparative studies for the development of pharmaceuticals and cosmetics.
      SUMMARY: The phytochemical screening showed consistent data with other studies of
      the genus HymenaeaBoth the vegetable part and the different extractive methods
      influenced significantly various parameters obtained in the various extracts,
      including the levels of phenolic compoundsThe barks of H. martiana presented the
      highest total phenolic and flavonoid contents.

PMID- 27695269
TI  - Elucidation of Flavonoids from Carissa congesta, Polyalthia longifolia, and
      Benincasa hispida Plant Extracts by Hyphenated Technique of Liquid Chromatography
      mass Spectroscopy.
AB  - BACKGROUND: Carissa congesta (CC), Polyalthia longifolia (PL), and Benincasa
      hispida (BH) are economically important plants. OBJECTIVE: Current research
      encompasses identification of quercetin and rutin and their analogues by liquid
      chromatography-mass spectroscopy (LC-MS) from the selected plant species.
      MATERIALS AND METHODS: Fresh roots, leaves, and seeds of CC, PL, and BH plants
      respectively were shade-dried followed by extraction and elucidation of rutin and
      quercetin by LC-MS. RESULTS: Structural elucidation of CC, PL, and BH extracts
      revealed the presence of flavonoids such as quercetin (m/z 301) and rutin (m/z
      610) as the parent ions along with presence of close analogues such as quercetin
      O-hexoside, Vicenin 2, quercetin-3-O-xyloside/arabinoside, and quercetin-3-O
      glucoside were identified as fragments. CONCLUSIONS: Thus, CC, PL, and BH
      extracts revealed the presence of flavonoids belonging to the class of flavonols
      such as rutin and quercetin. SUMMARY: Quercetin and rutin were identified from CC
      roots, PL leaves and BH seeds by liquid chromatography-mass
      spectroscopy.Quercetin was characterized at (m/z 301) and rutin (m/z 610) as the
      parent ion peaks.Analogues such as quercetin-O-hexoside, Vicenin 2 and quercetin
      3-O-glucoside were identified as fragments.

PMID- 27695268
TI  - Anti-Advanced Glycation End-product and Free Radical Scavenging Activity of
      Plants from the Yucatecan Flora.
AB  - BACKGROUND: Formation and accumulation of advanced glycation end-products (AGE)
      is recognized as a major pathogenic process in diabetic complications,
      atherosclerosis and cardiovascular diseases. In addition, reactive oxygen species
      and free radicals have also been reported to participate in AGE formation and in
      cell damage. Natural products with antioxidant and antiAGE activity have great
      therapeutic potential in the treatment of diabetes, hypertension and related
      complications. Objective: to test ethanolic extracts and aqueous-traditional
      preparations of plants used to treat diabetes, hypertension and obesity in
      Yucatecan traditional medicine for their anti-AGE and free radical scavenging
      activities. MATERIALS AND METHODS: ethanolic extracts of leaves, stems and roots
      of nine medicinal plants, together with their traditional preparations, were
      prepared and tested for their anti-AGE and antioxidant activities using the
      inhibition of advanced glycation end products and DPPH radical scavenging assays,
      respectively. RESULTS: the root extract of C. fistula (IC50= 0.1 mg/mL) and the
      leaf extract of P. auritum (IC50= 0.35 mg/mL) presented significant activity
      against vesperlysine and pentosidine-like AGE. Although none of the aqueous
      traditional preparations showed significant activity in the anti-AGE assay, both
      the traditional preparations and the ethanolic extracts of E. tinifolia, M.
      zapota, O. campechianum and P. auritum showed significant activity in the DPPH
      reduction assay. CONCLUSIONS: the results suggest that the metabolites
      responsible for the detected radical-scavenging activity are different to those
      involved in inhibiting AGE formation; however, the extracts with antioxidant
      activity may contain other metabolites which are able to prevent AGE formation
      through a different mechanism. SUMMARY: Ethanolic extracts from nine plants used
      to treat diabetes, hypertension and obesity in Yucatecan traditional medicine
      were tested for their anti-AGE and free radical scavenging activities.Significant
      activity against vesperlysine and pentosidine-like AGE was detected in the root
      extract of Cassia fistula and the leaf extract of Piper auritum.Traditional
      preparations and the ethanolic extracts of Ehretia tinifolia, Manilkara zapota,
      Ocimum campechianum and Piper auritum showed significant activity in the DPPH
      reduction assay.Results suggest that the metabolites responsible for the detected
      radical-scavenging activity are different to those involved in inhibiting AGE
      formation. Abbreviations Used: AGE: Advanced glycation end-product; DPPH: 2,2
      Diphenyl-1-picrylhydrazyl; DM: Diabetes mellitus; ROS: Reactive oxygen species;
      BSA: Bovine serum albumin; EtOH: Ethanol; EtOAc: Ethyl acetate; ANOVA: Analysis
      of variance; BA: Brosimum alicastrum; BS: Bunchosia swartziana; CF: Cassia
      fistula; CN: Cocos nucifera; ET: Ehretia tinifolia; MZ: Manilkara zapota; OC:
      Ocimum campechianum; PA: Piper auritum; RM: Rhizophora mangle; L: Leaves; S:
      Stems; R: Roots; T: traditional preparation; I: Inflorescences; W: Water.

PMID- 27695270
TI  - Bioactivity of Diterpens from the Ethyl Acetate Extract of Kingiodendron pinnatum
      Rox. Hams.
AB  - BACKGROUND: Kingiodendron pinnatum Rox. Hams. is an endangered medicinal plant
      used in gonorrhoe, catarrhal conditions of genito-urinary and respiratory tracts.
      The scientific and pharmacological formulation of K. pinnatum has not been
      established so far though it is being traditionally used by tribes of the region.
      OBJECTIVE: P hytochemical screening and identification of the bioactive compounds
      from the ethyl acetate extract of Kingiodendron pinnatum Rox. Hams. MATERIALS AND
      METHODS: Chromatographic separation was carried out by thin layer chromatography
      and column chromatography. Bio-autography of the column fractioned extract and
      TLC chromatogram were evaluated in vitro for antibacterial activity. The PTLC, HP
      TLC were used for crude extract and HPLC, LCMS, FTIR, 1HNMR and 13CNMR were
      employed for the isolated compound in the ethyl acetate extract of K. pinnatum.
      RESULTS: Evaluation of solvent system for chromatographic separation revealed
      that ethyl acetate: petroleum ether in the ratio of 7:2.5 ml was the most
      appropriate one for the separation of diterpene compounds. The antibacterial bio
      autography screening of TLC separated compound showed positive activity with
      Staphylococcus aureus and negative activity with Escherichia coli. Spectroscopic
      analysis of the isolated compound from the ethyl acetate extract of K. pinnatum
      revealed the presence of diterpene compound. CONCLUSION: It is evident from the
      present study that the ethyl acetate extract of K. pinnatum is rich in diterpene
      compounds and having potential antibacterial activity. SUMMARY: Novel extraction
      method for phytochemicls from Kingidendron pinnatum at RTAntibacterial property
      of diterpens extracted from Kingiodendron pinnatum Rox. Hams aganist S. aureus
      Abbreviations Used: TLC: Thin Layer Chromatography, PTLC: Preparatory Thin Layer
      Chromatography, HPTLC: High perormence Thin Layer chromatography, HPLC: High
      Performance Liquid Chromatography, LC-MS: Liquid chromatography Mass Spectra,
      FTIR: Fourier Transform Infrared Chromatography, NMR: Nuclear Magnetic Resonance.

PMID- 27695271
TI  - Inhibition of Human Cytochrome P450 2c8-catalyzed Amodiaquine N-desethylation:
      Effect of Five Traditionally and Commonly Used Herbs.
AB  - BACKGROUND: In Southeast Asia and many parts of the world, herbal products are
      increasingly used in parallel with modern medicine. OBJECTIVE: This study aimed
      to investigate the effects of herbs commonly used in Southeast Asia on activity
      of cytochrome P450 2C8 (CYP2C8), an important human hepatic enzyme in drug
      metabolism. MATERIALS AND METHODS: The selected herbs, such as Eurycoma
      longifolia Jack (ELJ), Labisia pumila (LP), Echinacea purpurea (EP), Andrographis
      paniculata (AP), and Ginkgo biloba (GB), were subjected to inhibition studies
      using an in vitro CYP2C8 activity marker, amodiaquine N-desethylase assay.
      Inhibition parameters, inhibitory concentration 50% (IC50), and Ki values were
      determined to study the potency and mode of inhibition. RESULTS: All herbs
      inhibited CYP2C8 with the following order of potency: LP > ELJ > GB > AP > EP. LP
      and ELJ inhibited potently at Ki's of 2 and 4 times the Ki of quercetin, the
      positive control. The inhibition by LP was uncompetitive in nature as compared to
      competitive or mixed type inhibition observed with other herbs. GB exhibited
      moderate inhibitory effect at a Ki6 times larger than quercetin Ki. AP and EP, on
      the other hand, showed only weak inhibition. CONCLUSION: The herbs we chose
      represented the more commonly used herbs in Southeast Asia where collision of
      tradition and modernization in healthcare, if not properly managed, may lead to
      therapeutic misadventures. We conclude that concurrent consumption of some herbs,
      in particular, LP and ELJ, may have relevance in drug-herb interactions via
      CYP2C8 inhibition in vivo. SUMMARY: Herbs are increasingly used in parallel with
      modern medicines nowadays. In this study five commonly used herbs in Southeast
      Asia region, ELJ, LP, EP, AP and GB, were investigated for their in vitro
      inhibitory potency on CYP2C8, an important drug-metaboliz-ing human hepatic
      enzyme. All herbs inhibited CYP2C8 activity marker, amodiaquine N-desethylation,
      with potency order of LP > ELJ > GB >AP > EP. LP, ELJ and GB exhibited Ki values
      of 2, 4 and 6 times the Ki of quercetin, the positive control, indicating potent
      to moderate degree of enzyme inhibition. AP and EP, on the other hand, showed
      only weak inhibition. In summary, concurrent consumption of some herbs especially
      LP and ELJ may have relevance in drug-herb interactions via CYP2C8 inhibition in
      vivo. Abbreviations Used: AQ: Amodiaquine, AP: Andrographis paniculata, CYP:
      Cytochrome P450, DEAQ: Desethylamodiaquine, EP: Echinacea purpurea, ELJ: Eurycoma
      longifolia Jack, GB: Ginkgo biloba, Ki: Inhibition constant, LP: Labisia pumila,
      Vmax: Maximal velocity, Km: Michaelis-Menten constant.

PMID- 27695272
TI  - Wound Healing Activity of Silibinin in Mice.
AB  - BACKGROUND: Silibinin is a semi-purified fraction of silymarin contained in milk
      thistle (Silybum marianum Asteraceae). Primarily known for its hepatoprotective
      actions, silymarin may also stimulate epithelialization and reduce inflammation
      in excision wound. Previous studies show antioxidant, anti-inflammatory, and
      antimicrobial actions of silibinin. However, wound healing property of silibinin
      is not well studied. OBJECTIVE: This study investigates wound healing activity of
      silibinin topical formulation. MATERIALS AND METHODS: Wound healing activity of
      0.2% silibinin gel was assessed by incision and excision wound models in mice.
      Animals were divided into gel base, silibinin gel, and Mega Heal gel(r) treated
      groups with six animals in each group. Wound contraction, wound tissue tensile
      strength, and hydroxyproline content were measured, and histopathological
      evaluation of wound tissue of all the above treatment groups was carried out.
      RESULTS: Application of 0.2% silibinin hydrogel for 8 days led to 56.3% wound
      contraction compared to 64.6% using standard Mega Heal gel with a subsequent
      increase in hydroxyproline content, which was significantly higher (P < 0.001)
      over control animals showing 33.2% contraction. After 14 days, percentage of
      contraction reached 96.1%, 97.6%, and 86.7%, respectively. Wound tissue tensile
      strength with silibinin (223.55 +/- 3.82 g) and standard (241.38 +/- 2.49 g) was
      significantly higher (P < 0.001) than control (174.06 +/- 5.75 g). Histopathology
      of silibinin and standard gel treated wound tissue showed more fibroblasts, fewer
      macrophage infiltration, and well-formed collagen fibers. CONCLUSION: Here, we
      show potent wound healing activity of silibinin hydrogel formulation. SUMMARY:
      0.2% silibinin hydrogel showed potent wound healing activity in incision and
      excision wound models in mice. Abbreviations Used: ROS: Reactive oxygen species.

PMID- 27695273
TI  - Antihyperglycemic and Insulin Secretagogue Activities of Abrus precatorius Leaf
      Extract.
AB  - AIM: Abrus precatorius leaves methanolic extract (APME) was evaluated for in vivo
      antihyperglycemic activity and in vitro insulinotropic effect. MATERIALS AND
      METHODS: In vivo antihyperglycemic and insulin secretagogue activities were
      assessed in streptozotocin-induced diabetic rats by oral administration of APME
      (200 mg/kg body weight [bw]) for 28 days. In vitro insulin secretion mechanisms
      were studied using mouse insulinoma beta cells (MIN6-beta). In vivo body weight
      and blood glucose and in vivo and in vitro insulin levels were estimated.
      RESULTS: In diabetic rats, APME treatment significantly restored body weight
      (26.39%), blood glucose (32.39%), and insulin levels (73.95%) in comparison to
      diabetic control rats. In MIN6-beta cells, APME potentiated insulin secretion in
      a dependent manner of glucose (3-16.7 mM) and extract (5-500 MUg/mL)
      concentration. Insulin secretagogue effect was demonstrated in the presence of 3
      isobutyl-1-methyl xanthine, glibenclamide, elevated extracellular calcium, and K+
      depolarized media. Insulin release was reduced in the presence of nifedipine,
      ethylene glycol tetra acetic acid (calcium blocking agents), and diazoxide
      (potassium channel opener). CONCLUSION: The study suggests that APME
      antihyperglycemic activity might involve the insulin secretagogue effect by
      pancreatic beta cells physiological pathways via K+-ATP channel dependent and
      independently, along with an effect on Ca2+ channels. SUMMARY: Abrus precatorius
      leaves methanolic extract (APME) showed a significant anti hyperglycemic and
      insulin secretagogue activities in streptozotocin induced diabetic rats. Also
      demonstrated a potent In vitro insulin secretagogue effect in mouse insulinoma
      beta cells (MIN6-beta)APME treatment significantly restored body weight (26.39%),
      reduced blood glucose (32.39%) and enhanced circulatory insulin levels (73.95%)
      in diabetic ratsAPME demonstrated glucose and extract dose dependent insulin
      secretionInsulin secretagogue effect was demonstrated in the presence of 3
      isobutyl-1-methyl xanthine, glibenclamide, elevated extracellular calcium and K+
      depolarized media. Insulin release was reduced in the presence of nifedipine and
      ethylene glycol tetra acetic acid (Calcium blocking agents), diazoxide (potassium
      channel opener)The insulinotropic effect of APME involves a physiologic effect on
      K+-ATP channel and Ca2+ channels Abbreviations Used: ANOVA: Analysis of variance,
      CMC: Carboxy methyl cellulose, cAMP: Cyclic adenosine monophosphate, CaCl:
      Calcium chloride, AP: Abrus precatorius, APME: Abrus precatorius methanolic
      extract, DMEM: Dulbecco's modified Eagle's medium, DMSO: Dimethyl sulphoxide,
      EGTA: Ethylene glycol tetra acetic acid, FCS: Fetal calf serum, IBMX: 3-Isobutyl
      1-methylxanthine, KCl: Potassium chloride, KRB: Kreb's Ringer buffer, MIN6: Mouse
      insulinoma cell line, MTT: 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium
      Bromide, STZ: Streptozotocin.

PMID- 27695274
TI  - Effects of Curcuma xanthorrhiza Extracts and Their Constituents on Phase II Drug
      metabolizing Enzymes Activity.
AB  - BACKGROUND: Curcuma xanthorrhiza is a native Indonesian plant and traditionally
      utilized for a range of illness including liver damage, hypertension, diabetes,
      and cancer. OBJECTIVE: The study determined the effects of C. xanthorrhiza
      extracts (ethanol and aqueous) and their constituents (curcumene and
      xanthorrhizol) on UDP-glucuronosyltransferase (UGT) and glutathione transferase
      (GST) activities. MATERIALS AND METHODS: The inhibition studies were evaluated
      both in rat liver microsomes and in human recombinant UGT1A1 and UGT2B7 enzymes.
      p-nitrophenol and beetle luciferin were used as the probe substrates for UGT
      assay while 1-chloro-2,4-dinitrobenzene as the probe for GST assay. The
      concentrations of extracts studied ranged from 0.1 to 1000 MUg/mL while for
      constituents ranged from 0.01 to 500 MUM. RESULTS: In rat liver microsomes, UGT
      activity was inhibited by the ethanol extract (IC50 =279.74 +/- 16.33 MUg/mL).
      Both UGT1A1 and UGT2B7 were inhibited by the ethanol and aqueous extracts with
      IC50 values ranging between 9.59-22.76 MUg/mL and 110.71-526.65 MUg/Ml,
      respectively. Rat liver GST and human GST Pi-1 were inhibited by ethanol and
      aqueous extracts, respectively (IC50 =255.00 +/- 13.06 MUg/mL and 580.80 +/-
      18.56 MUg/mL). Xanthorrhizol was the better inhibitor of UGT1A1 (IC50 11.30 +/-
      0.27 MUM) as compared to UGT2B7 while curcumene did not show any inhibition. For
      GST, both constituents did not show any inhibition. CONCLUSION: These findings
      suggest that C. xanthorrhiza have the potential to cause herb-drug interaction
      with drugs that are primarily metabolized by UGT and GST enzymes. SUMMARY:
      Findings from this study would suggest which of Curcuma xanthorrhiza extracts and
      constituents that would have potential interactions with drugs which are highly
      metabolized by UGT and GST enzymes. Further clinical studies can then be designed
      if needed to evaluate the in vivo pharmacokinetic relevance of these interactions
      Abbreviations Used: BSA: Bovine serum albumin, CAM: Complementary and alternative
      medicine, cDNA: Complementary deoxyribonucleic acid, CDNB: 1-Chloro-2,4
      dinitrobenzene, CuSO4.5H2O: Copper(II) sulfate pentahydrate, CXEE: Curcuma
      xanthorrhiza ethanol extract, CXAE: Curcuma xanthorrhiza aqueous extract, GC-MS:
      Gas chromatography-mass spectroscopy, GSH: Glutathione, GST: Glutathione S
      transferase, KCl: Potassium chloride, min: Minutes, MgCl2: Magnesium chloride,
      mg/mL: Concentration (weight of test substance in milligrams per volume of test
      concentration), mM: Milimolar, Na2CO3: Sodium carbonate, NaOH: Sodium hydroxide,
      nmol: nanomol, NSAIDs: Non-steroidal antiinflammatory drug, p-NP: para
      nitrophenol, RLU: Relative light unit, SEM: Standard error of mean, UDPGA: UDP
      glucuronic acid, UGT: UDP-glucuronosyltransferase.

PMID- 27695275
TI  - Implementing the Five-A Model of Technical Refinement: Key Roles of the Sport
      Psychologist.
AB  - There is increasing evidence for the significant contribution provided by sport
      psychologists within applied coaching environments. However, this rarely
      considers their skills/knowledge being applied when refining athletes' already
      learned and well-established motor skills. Therefore, this article focuses on how
      a sport psychologist might assist a coach and athlete to implement long-term
      permanent and pressure proof refinements. It highlights key contributions at each
      stage of the Five-A model-designed to deliver these important outcomes-providing
      both psychomotor and psychosocial input to the support delivery. By employing
      these recommendations, sport psychologists can make multiple positive
      contributions to completion of this challenging task.

PMID- 27695276
TI  - Structure of the male copulatory apparatus in Prognathorhynchus busheki
      (Platyhelminthes, Kalyptorhynchia).
AB  - Gnathorhynchidae is a diverse taxon of predatory eukalyptorhynch flatworms
      characterized by an armed proboscis. Their present taxonomy is not concordant
      with what we know of their phylogeny. Further progress in this area is hindered
      by a lack of information concerning their morphology. As recent studies have
      shown, a historical reliance on live observations for species descriptions has
      resulted in a number of errors and omissions. Here, we redescribe the anatomy of
      the male copulatory organ of Prognathorhynchus busheki using transmission
      electron and confocal microscopy, correcting several errors in the original
      description. Furthermore, we use these results to update our understanding of the
      anatomy and evolution of male copulatory organs in Gnathorhynchidae and in
      Platyhelminthes more generally.

PMID- 27695277
TI  - The origins of Western mind-body exercise methods.
AB  - Background: Over recent decades, mind-body exercise methods have gained
      international popularity and importance in the management of musculoskeletal
      disorders. Objectives: The scope of this paper was to investigate: the origins of
      Western mind-body methods, their philosophies, exercises, and relationship with
      mainstream healthcare over the last two centuries. Major findings: Within a few
      decades of the turn of the 20th century, a cluster of mind-body exercise methods
      emerged from at least six pioneering founders: Checkley, Muller, Alexander,
      Randell, Pilates, and Morris. Each was based upon a similar exercise philosophy
      and similar functional movement-harmonizing exercises. This renaissance of
      independent mind-body schools occurred in parallel with the demise of the 18th
      and 19th century gymnasium Physical Culture movement and the concurrent emergence
      of bodybuilding and strength training. Even though mostly forgotten today,
      Western mind-body exercise methods enjoyed celebrated success during the first
      half of the 20th century, were hailed by medical and allied health practitioners
      and practiced by millions from society's elite to deprived minorities.
      Conclusions: Rediscovering the Western mind-body exercise movement is hoped to
      facilitate official healthcare establishment recognition of this kind of training
      as an integral entity. This may widen research opportunities and consolidate
      approaches toward: optimal musculoskeletal rehabilitation and injury prevention,
      promotion of a healthy active lifestyle environment in the modern world, and
      enhancement of the natural pain-free human athletic look, feel, and performance.

PMID- 27695278
TI  - Vitamin D Deficiency in Egyptian Systemic Lupus Erythematosus Patients: How
      Prevalent and Does It Impact Disease Activity?
AB  - BACKGROUND: The emerging role of vitamin D in immunology and autoimmune disorders
      has been a worldwide interest in the last decade. Systemic lupus erythematosus
      (SLE) patients are particularly at a delicate position predisposing them to
      suffer from vitamin D deficiency due to the multiple risk factors accompanying
      the disease. Whether vitamin D deficiency is also involved as a risk factor for
      developing SLE and affecting its course is a considerable concern. OBJECTIVES:
      The objective of this study was to estimate the prevalence of vitamin D
      deficiency in SLE patients and its relation to disease. MATERIALS AND METHODS: In
      our observational cross-sectional study, serum levels of vitamin D [25(OH)D] in
      60 SLE patients and 30 age- and sex-matched healthy controls were assessed and
      estimated for deficiency and insufficiency at 10 and 30 ng/mL, respectively.
      Disease activity was evaluated by SLE disease activity index (SLEDAI),
      irreversible organ damage by Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI), and
      severity by Severity of Disease Index. Fatigue was measured by visual analog
      scale. RESULTS: Significantly lower levels of 25(OH)D were found in SLE patients
      (17.6 +/- 6.9 ng/mL) in comparison to controls (79.0 +/- 28.7 ng/mL), with a
      statistically high significant difference (t = -11.2, P < 0.001). High prevalence
      of vitamin D insufficiency and deficiency was detected as 73.3% and 23.3%,
      respectively. Vitamin D had a highly significant negative correlation with SLEDAI
      (r = -0.495, P < 0.001), SLICC (r = -0.431, P < 0.05), and fatigue (r = -0.436, P
      < 0.05). CONCLUSION: Vitamin D deficiency and insufficiency were found to be
      prevalent in SLE patients in our study and related to disease activity and
      fatigue. If needed, routine screening and consequent repletion of vitamin D are
      recommended in SLE patients. Restoring adequate vitamin D levels in SLE patients
      should be more explored as a potential yet simple measure to their usual
      management to improve their condition.

PMID- 27695279
TI  - Acute vision loss and choroidal filling delay in the absence of giant-cell
      arteritis.
AB  - Giant-cell arteritis (GCA) is a visually devastating disease that often
      progresses to severe bilateral vision loss if untreated. Diagnosis of GCA is made
      challenging by the protean nature of the disease and the lack of a simple test
      that is both highly sensitive and specific. Choroidal filling delay on
      fluorescein angiography (FA) has been touted as a highly characteristic feature
      of GCA-related vision loss, although knowledge of both the sensitivity and
      specificity of this finding remains unproven. We report our experience of delayed
      choroidal filling on FA in a series of seven patients referred to an academic
      neuro-ophthalmology practice due to concern for GCA. Despite the FA findings, our
      examination, diagnostic testing, and long-term follow-up excluded the diagnosis
      of GCA in all cases, suggesting that choroidal perfusion abnormalities may occur
      in the absence of GCA. When evaluating a patient for acute vision loss, the
      astute clinician must remain cognizant of the limitations of FA in the diagnosis
      of GCA.

PMID- 27695280
TI  - Clinical evaluation of a trabecular microbypass stent with phacoemulsification in
      patients with open-angle glaucoma and cataract.
AB  - PURPOSE: To evaluate the safety and efficacy of the iStent trabecular microbypass
      stent in combination with cataract surgery in patients with open-angle glaucoma
      (OAG). METHODS: Retrospective, consecutive case series from October 2012 to
      December 2015 with no exclusion criteria. The series comprised of 350 eyes with
      OAG and cataract. Data were collected both preoperatively and postoperatively at
      day 1 week 1, months 1, 3, 6, 12, 18, and 24. Data included intraocular pressure
      (IOP), number of glaucoma medications, visual acuity, the incidence of
      postoperative IOP pressure spikes of greater than >=15 mmHg at any time point,
      and need for additional surgery. RESULTS: The mean preoperative IOP was 19.13+/
      6.34 mmHg. At 2 years postoperation, mean IOP was 15.17+/-3.53 mmHg (P<0.0001).
      The mean number of glaucoma medications was 1.19+/-1.00 preoperatively and 0.61+/
      0.96 (P<0.0001) at 2 years postoperation. At 1 day postoperatively, 31 eyes
      (12.4%) experienced an IOP increase of 15 mmHg above their baseline IOP that
      responded to topical therapy. Two patients required additional tube shunt
      surgery. CONCLUSION: The insertion of the iStent trabecular microbypass stent in
      combination with cataract surgery effectively lowers IOP in OAG patients. The
      magnitude of IOP reduction was more significant in patients with higher
      preoperative pressure. Medication use was also significantly reduced
      postoperatively. The safety profile appears favorable with a low rate of IOP
      spikes and only two eyes (<1%) requiring additional surgery.

PMID- 27695281
TI  - Intravenous paracetamol and intraocular pressure reduction: mannitol may also be
      involved.

PMID- 27695282
TI  - Cosmetic and functional outcomes of frontalis suspension surgery using autologous
      fascia lata or silicone rods in pediatric congenital ptosis.
AB  - PURPOSE: Cosmetic and functional outcomes of frontalis suspension surgery using
      autologous fascia lata (FL) or silicone rods (SRs) in pediatric congenital
      ptosis. DESIGN: Retrospective case series. STUDY SUBJECTS: Patients with
      congenital ptosis, aged 18 years or younger, during the period under study (2005
      2011) at the Singapore National Eye Centre. METHODS: Review of case records for
      functional and cosmetic outcome measures after frontalis suspension surgery using
      either SRs or autologous FL. RESULTS: A total of 18 patients were studied (14
      eyelids had FL, 16 eyelids had SRs) with mean ages of 7.1 (range 5-12) and 7.2
      (range 4-18) years for the FL and SR groups, respectively. Mean follow-up period
      was 41.6 (range 11.2-77.9) and 48.6 (16.1-87.4) months, respectively. Patients in
      the FL group had better functional and cosmetic results compared to those in
      silicone group, with no recurrence of ptosis. More complications were experienced
      by patients in the SR group. CONCLUSION: Autologous FL for frontalis suspension
      remains an excellent choice for (and should be considered as useful surgical
      armamentarium for) repair of severe congenital ptosis.

PMID- 27695283
TI  - Agreement of noninvasive tear break-up time measurement between Tomey RT-7000
      Auto Refractor-Keratometer and Oculus Keratograph 5M.
AB  - BACKGROUND: It is difficult to standardize assessment of dry eye in different
      clinical settings. Increasingly, tear stability is recognized to be important for
      the definition and assessment of patients with dry eye. Recently, two
      commercially available instruments have been made available for objectively
      measuring noninvasive tear break-up time (NIBUT), as an indicator of tear
      stability: the Tomey RT-7000 Auto Refractor-Keratometer and Oculus Keratograph
      (K)5M. We aim to assess the agreement of NIBUT measurements using these
      modalities. METHODS: This prospective cross-sectional study was carried out in a
      tertiary referral eye center and involved 126 consecutive dry eye patients. NIBUT
      assessment was performed on the right eyes of participants with both the RT-7000
      and the K5M techniques, with the order of assessment randomized. The Standardized
      Patient Evaluation of Eye Dryness (SPEED) questionnaires were administered to
      assess dry eye symptoms in the 2 weeks before assessment. RESULTS: The age of the
      participants was 56.0+/-14.3 years (69.84% females). Measurements for both
      modalities were non-normally distributed (right-skewed). The median RT-7000 and
      K5M readings were 4.2 (range 0.1-10.0) and 6.4 (0.1-24.9) seconds, respectively.
      RT-7000 and K5M readings were poorly correlated (rho=0.061, P=0.495). Intraclass
      correlation coefficient between the modalities was 0.187 (95% confidence interval
      -0.097 to 0.406). The Bland-Altman plot showed no systematic differences between
      the readings with these machines. The agreement between machines was not
      different in different SPEED categories. CONCLUSION: While there are theoretical
      and practical benefits of NIBUT for assessment of tear stability over dye-based
      methods, the agreement between the two modalities was poor. Hence, studies and
      trials assessing NIBUT should avoid using these modalities interchangeably for
      NIBUT assessment. More research is needed to improve consensus on how to
      determine NIBUT.

PMID- 27695284
TI  - Noninvasive detection of microaneurysms in diabetic retinopathy by swept-source
      optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVES: A method of identifying retinal vascular
      microaneurysms (MAs) in nonproliferative diabetic retinopathy (NPDR) using swept
      source optical coherence tomography (SS-OCT). PATIENTS AND METHODS: SS-OCT images
      were acquired in 17 eyes with NPDR using prototype SS-OCT device and fluorescein
      angiography (FA) images were obtained simultaneously. MAs identified on SS-OCT
      slabs were correlated to MAs identified on FA. RESULTS: MAs were identified in SS
      OCT slabs in 15/17 eyes, resulting in NPDR diagnosis rate of 88%. Mean number of
      MAs identified on FA was 11.7+/-11.9 (total 199) and was 8.1+/-9.3 (total 137) on
      SS-OCT. Wilcoxon rank sum test showed no significant difference in MAs detected
      on SS-OCT and FA (P=0.2995) across eyes. Wilcoxon rank sum test showed SS-OCT
      detected slightly fewer MAs than FA per eye (3.65 less, P=0.0009). CONCLUSION: SS
      OCT visualization of MAs could serve as a tool for diagnosing NPDR, and possibly
      applied as an imaging biomarker for population-based diabetic retinopathy
      screening.

PMID- 27695285
TI  - The association of hematologic inflammatory markers with atherogenic index in
      type 2 diabetic retinopathy patients.
AB  - BACKGROUND: Atherogenic dyslipidemia is particularly common in people with type 2
      diabetes (DM2). Platelets from patients with DM2 have increased reactivity and
      baseline activation. The aim of the present study is to evaluate the relationship
      between atherogenic index and hematologic inflammatory markers and to evaluate
      the relationship between these parameters and associated variables in diabetic
      retinopathy (DR) patients. METHODS: The medical records of all patients admitted
      to the eye clinic between January and December 2014 were evaluated
      systematically. Laboratory parameters of 278 outpatients with DM2 diagnosed after
      the age of 30 years and 107 healthy subjects were analyzed. RESULTS: The DM2 + DR
      group consisted of 120 patients (47 males and 73 females; mean age 59.8+/-9.2
      years). The DM2 without DR group consisted of 158 patients (59 males and 99
      females; mean age 57.3+/-12.2 years). Mean platelet volume, platelet distribution
      width (PDW), platelet-lymphocyte (P/L) ratio, triglycerides, and atherogenic
      index were higher in DM2 patients than in control patients, but there was no
      difference between the DM2 + DR and the DM2 without DR groups. Only P/L ratio was
      different in the DM2 + DR patients compared to the DM2 without DR patients.
      Hemoglobin A1c levels correlated very weakly with the mean platelet volume, PDW,
      P/L ratio, and the red cell distribution width. The atherogenic index was very
      weakly correlated with the P/L ratio, PDW, and red cell distribution width.
      CONCLUSION: Dyslipidemia-induced inflammation contributes to pathological
      processes that lead to retinopathy in DR patients.

PMID- 27695286
TI  - Corneal stromal demarcation line after collagen cross-linking in corneal ectatic
      diseases: a review of the literature.
AB  - Collagen cross-linking (CXL) is a relatively new conservative approach for
      progressive corneal ectasia, which is able to strengthen corneal tissue reforming
      new covalent bonds. Subjective and objective results following this method seem
      to be promising. In recent years, newer CXL protocols have been developed to
      perform more effective and less invasive procedures. The increasing diffusion of
      CXL in the corneal ectatic disease has increased the need to have actual indices
      regarding the efficacy of the treatment. Evaluation of demarcation line (DL), a
      transition zone between the cross-linked anterior corneal stroma and the
      untreated posterior corneal stroma, is considered a measurement of the depth of
      CXL treatment into the stroma. Some evidence in the literature emphasize that DL
      could be a measure of effectiveness of the CXL. On the contrary, some authors
      believe that the "the deeper, the better" principle is rather a simplistic
      approach for interpreting the clinical importance of the corneal stromal DL.

PMID- 27695287
TI  - Longevity results of modified Hughes procedure in reconstructing large lower
      eyelid defects.
AB  - PURPOSE: The purpose of this study was to evaluate the longevity results of
      modified Hughes procedure in reconstructing large lower eyelid defects.
      BACKGROUND: The modified Hughes procedure was used to reconstruct large full
      thickness lower eyelid defects. Meanwhile, the functional results indicated that
      ocular surface health in the treated eyes may be affected. PATIENTS AND METHODS:
      Noncomparative, case series retrospective study was designed after obtaining the
      approval of the institutional review board at the Ophthalmology Department,
      Menoufia University, Egypt, where the results of cases who underwent surgery with
      the modified Hughes procedure during a 7-year interval were evaluated. RESULTS:
      Eleven patients (seven males and four females) in the age range 59-77 years (mean
      age 67+/-5 years) were identified. The follow-up ranged from 12 months to 48
      months. Cosmetic, functional, and postoperative results were analyzed.
      CONCLUSION: Despite the favorable cosmetic results of the Hughes
      tarsoconjunctival flap, the procedure has its own limitations. The results
      indicated that it does affect the functions and tear film stability in the
      treated eyes.

PMID- 27695288
TI  - Eltrombopag for the treatment of aplastic anemia: current perspectives.
AB  - Aplastic anemia (AA) is a potential life-threatening hematopoietic stem cell
      (HSC) disorder resulting in cytopenia. The mainstays of treatment for AA are
      definitive therapy to restore HSCs and supportive measures to ameliorate
      cytopenia-related complications. The standard definitive therapy is HSC
      transplantation for young and medically fit patients with suitable donors and
      immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine for
      the remaining patients. A significant proportion of patients are refractory to
      IST or relapse after IST. Various strategies have been explored in these
      patients, including second course of antithymocyte globulin, high-dose
      cyclophosphamide, and alemtuzumab. Eltrombopag, a thrombopoietin mimetic, has
      recently emerged as an encouraging and promising agent for patients with
      refractory AA. It has demonstrated efficacy in restoring trilineage
      hematopoiesis, and this positive effect continues after discontinuation of the
      drug. There are ongoing clinical trials exploring the role of eltrombopag as a
      first-line therapy in moderate to severe AA and a combination of eltrombopag with
      IST in severe AA.

PMID- 27695290
TI  - Protein kinase C-mediated sodium glucose transporter 1 activation in precondition
      induced cardioprotection.
AB  - The concept of cardioprotection through preconditioning against ischemia
      reperfusion (I/R) injury is well known and established. However, among different
      proposed mechanisms regarding the concept of ischemic preconditioning, protein
      kinase C (PKC)-mediated cardioprotection through ischemic preconditioning plays a
      key role in myocardial I/R injury. Thus, this study was designed to find the
      relationship between PKC and sodium glucose transporter 1 (SGLT1) in
      preconditioning-induced cardioprotection, which is ill reported till now. By
      applying a multifaceted approach, we demonstrated that PKC activates SGLT1, which
      curbed oxidative stress and apoptosis against I/R injury. PKC activation enhances
      cardiac glucose uptake through SGLT1 and seems essential in preventing I/R
      induced cardiac injury, indicating a possible cross-talk between PKC and SGLT1.

PMID- 27695289
TI  - Gender differences in the adverse events' profile registered in seven
      observational studies of a wide gender-medicine (MetaGeM) project: the MetaGeM
      safety analysis.
AB  - BACKGROUND: MetaGeM is a wide gender-medicine project comprising post hoc and
      meta-analyses by gender of clinical outcomes, therapeutic approaches, and safety
      data from previously conducted observational studies to explore possible gender
      differences in real-life clinical settings. We report the results of the safety
      meta-analysis of seven MetaGeM studies, evaluating gender differences in adverse
      event (AE) incidence and severity. METHODS: Data were collected between February
      2002 and July 2013. Male and female patients were compared for the main safety
      variables, using Student's t-test, chi2 test, or Fisher's exact test as
      appropriate. As supportive analysis, a logistic regression model was estimated to
      evaluate associations between gender and outcome. RESULTS: In total, 4,870
      patients (46% females, 54% males) were included in the analysis; age was higher
      for females (mean +/- standard deviation 61.2+/-18.3 years) than males (56.3+/
      16.6 years). Overall, 264 AEs were reported (59.1% in males). There were no
      significant gender differences in the percentage of patients with at least one
      AE: 3.0% for females versus 3.9% for males, chi2 test P>0.05. According to the
      logistic regression model results, no association between gender and AEs
      occurrence seems to exist. A statistically significant gender difference in the
      percentage of drug-related AEs emerged (37.6% in females vs 20.8% in males,
      chi2P=0.0039). Slightly significantly more AEs in females were addressed with
      treatment compared with males (78.1% vs 66.7%, chi2P=0.0485). Total serious AEs
      (SAEs) were 47 (72% in males). The frequency of patients with >=1 SAE was 0.6% in
      females versus 1.2% in males (chi2 test P=0.0246). CONCLUSION: This safety
      analysis on a large sample of almost 5,000 patients with different diseases and
      treated with a wide range of different drugs provides a useful overview on
      possible gender differences in drug tolerability, which may be helpful in more
      accurately designing future clinical trials from a gender-specific perspective.

PMID- 27695291
TI  - Effects of low-carbohydrate diet therapy in overweight subjects with autoimmune
      thyroiditis: possible synergism with ChREBP.
AB  - The thyroid is one of the metabolism regulating glands. Its function is to
      determine the amount of calories that the body has to burn to maintain normal
      weight. Thyroiditides are inflammatory processes that mainly result in autoimmune
      diseases. We have conducted the present study in order to have a clear picture of
      both autoimmune status and the control of body weight. We have evaluated the
      amount of either thyroid hormones, or antithyroid, or anti-microsomal, or anti
      peroxidase antibodies (Abs) in patients with high amounts of Abs. In a diet
      devoid of carbohydrates (bread, pasta, fruit, and rice), free from goitrogenic
      food, and based on body mass index, the distribution of body mass and
      intracellular and extracellular water conducted for 3 weeks gives the following
      results: patients treated as above showed a significant reduction of antithyroid
      (-40%, P<0.013), anti-microsomal (-57%, P<0.003), and anti-peroxidase (-44%,
      P<0,029) Abs. Untreated patients had a significant increase in antithyroid (+9%,
      P<0.017) and anti-microsomal (+30%, P<0.028) Abs. Even the level of anti
      peroxidase Abs increased without reaching statistical significance (+16%,
      P>0064). With regard to the body parameters measured in patients who followed
      this diet, reduction in body weight (-5%, P<0.000) and body mass index (-4%,
      P<0.000) were observed. Since 83% of patients with high levels of autoantibodies
      are breath test positive to lactase with a lactase deficit higher than 50%, this
      fact led us to hypothesize a correlation with carbohydrate-responsive element
      binding protein and therefore a possible role of carbohydrate metabolism in the
      development and maintenance of autoimmune thyroiditis associated with body weight
      increase and slower basic metabolism.

PMID- 27695292
TI  - A triazole derivative elicits autophagic clearance of polyglutamine aggregation
      in neuronal cells.
AB  - Trinucleotide CAG repeat expansion in the coding region of genes has a propensity
      to form polyglutamine (polyQ) aggregates that contribute to neuronal disorders.
      Strategies in elevating autophagy to disintegrate the insoluble aggregates
      without injuring cells have become a major goal for therapy. In this work, a
      triazole derivative, OC-13, was found accelerating autophagic clearance of polyQ
      aggregation in human neuroblastoma cells following induction of the enhanced
      green fluorescence-conjugated chimeric protein that enclosed 79 polyQ repeats
      (Q79-EGFP). OC-13 accelerated autophagy development and removed nuclear Q79-EGFP
      aggregates. The increase of Beclin-1, turnover of LC3-I to LC3-II and degradation
      of p62 supported autophagy activation. Pretreatment of autophagy inhibitor,
      bafilomycin A1, not only suppressed autophagolysome fusion, but also impeded
      aggregate eradication. The study also showed that c-Jun N-terminal kinase/Beclin
      1 pathway was activated during OC-13 treatment and c-Jun N-terminal kinase
      inhibitor impaired autophagy and final breakdown. Autophagic clearance of the
      insoluble aggregates demonstrated the feasibility of OC-13 in alleviating
      neuronal disorders because of expanded glutamine stretches.

PMID- 27695295
TI  - Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma:
      assessing the change from intravenous to subcutaneous administration of
      rituximab.
AB  - BACKGROUND: A subcutaneous (SC) formulation of rituximab (MabThera(r)/Rituxan(r))
      has been developed that could reduce administration time and improve patient
      satisfaction with treatment. The Rituximab Administration Satisfaction
      Questionnaire (RASQ) was created to assess patients' perceptions and satisfaction
      with rituximab SC (RASQ-SC) or rituximab intravenous (RASQ-IV). We assessed the
      content validity and psychometric properties of RASQ in patients with non-Hodgkin
      lymphoma. METHODS: Face and content validity of RASQ-SC and RASQ-IV were
      qualitatively assessed using 60-minute combined concept elicitation and cognitive
      debriefing interviews. Psychometric validation of RASQ (item performance and
      reliability) was assessed quantitatively against the established Cancer Therapy
      Satisfaction Questionnaire (CTSQ), using questionnaire data from the PrefMab
      (NCT01724021) and MabCute (NCT01461928) clinical studies. RESULTS: RASQ-IV
      demonstrated excellent coverage of concepts relevant to patients' (n=10) own
      treatment experiences and no new concepts were identified. Patients' expectations
      of rituximab SC were conceptually consistent with items included in the RASQ-SC,
      suggesting that the tool is also conceptually adequate. In 1,051 patients from
      PrefMab and MabCute, correlations with domains such as "RASQ: Physical Impacts"
      and "CTSQ: Feelings About Side Effects", "RASQ: Physical Impacts" and "CTSQ:
      Satisfaction With Therapy", and "RASQ: Satisfaction" and "CTSQ: Satisfaction With
      Therapy", achieved moderate-to-high correlations (>0.4) for convergent domains
      and <0.3 for divergent domains. CONCLUSION: This study supports the qualitative
      face and content validity and psychometric validity of RASQ-IV and RASQ-SC. Minor
      revisions were made to the questionnaires to enhance clarity and aid consistent
      reporting.

PMID- 27695293
TI  - Application of physiologically based pharmacokinetic modeling in predicting drug
      drug interactions for sarpogrelate hydrochloride in humans.
AB  - BACKGROUND: Evaluating the potential risk of metabolic drug-drug interactions
      (DDIs) is clinically important. OBJECTIVE: To develop a physiologically based
      pharmacokinetic (PBPK) model for sarpogrelate hydrochloride and its active
      metabolite, (R,S)-1-{2-[2-(3-methoxyphenyl)ethyl]-phenoxy}-3-(dimethylamino)-2
      propanol (M-1), in order to predict DDIs between sarpogrelate and the clinically
      relevant cytochrome P450 (CYP) 2D6 substrates, metoprolol, desipramine,
      dextromethorphan, imipramine, and tolterodine. METHODS: The PBPK model was
      developed, incorporating the physicochemical and pharmacokinetic properties of
      sarpogrelate hydrochloride, and M-1 based on the findings from in vitro and in
      vivo studies. Subsequently, the model was verified by comparing the predicted
      concentration-time profiles and pharmacokinetic parameters of sarpogrelate and M
      1 to the observed clinical data. Finally, the verified model was used to simulate
      clinical DDIs between sarpogrelate hydrochloride and sensitive CYP2D6 substrates.
      The predictive performance of the model was assessed by comparing predicted
      results to observed data after coadministering sarpogrelate hydrochloride and
      metoprolol. RESULTS: The developed PBPK model accurately predicted sarpogrelate
      and M-1 plasma concentration profiles after single or multiple doses of
      sarpogrelate hydrochloride. The simulated ratios of area under the curve and
      maximum plasma concentration of metoprolol in the presence of sarpogrelate
      hydrochloride to baseline were in good agreement with the observed ratios. The
      predicted fold-increases in the area under the curve ratios of metoprolol,
      desipramine, imipramine, dextromethorphan, and tolterodine following single and
      multiple sarpogrelate hydrochloride oral doses were within the range of >=1.25,
      but <2-fold, indicating that sarpogrelate hydrochloride is a weak inhibitor of
      CYP2D6 in vivo. Collectively, the predicted low DDIs suggest that sarpogrelate
      hydrochloride has limited potential for causing significant DDIs associated with
      CYP2D6 inhibition. CONCLUSION: This study demonstrated the feasibility of
      applying the PBPK approach to predicting the DDI potential between sarpogrelate
      hydrochloride and drugs metabolized by CYP2D6. Therefore, it would be beneficial
      in designing and optimizing clinical DDI studies using sarpogrelate as an in vivo
      CYP2D6 inhibitor.

PMID- 27695294
TI  - Combined computational and experimental studies of molecular interactions of
      albuterol sulfate with bovine serum albumin for pulmonary drug nanoparticles.
AB  - Albumin-based nanoparticles (NPs) are a promising technology for developing drug
      carrier systems, with improved deposition and retention profiles in lungs.
      Improved understanding of these drug-carrier interactions could lead to better
      drug-delivery systems. The present study combines computational and experimental
      methods to gain insights into the mechanism of binding of albuterol sulfate (AS)
      to bovine serum albumin (BSA) on the molecular level. Molecular dynamics
      simulation and surface plasmon resonance spectroscopy were used to determine that
      there are two binding sites on BSA for AS: the first of which is a high-affinity
      site corresponding to AS1 and the second of which appears to represent the
      integrated functions of several low-affinity sites corresponding to AS2, AS3, and
      AS8. AS1 was the strongest binding site, established via electrostatic
      interaction with Glu243 and Asp255 residues in a hydrophobic pocket. Hydrogen
      bonds and salt bridges played a main role in the critical binding of AS1 to BSA,
      and water bridges served a supporting role. Based upon the interaction mechanism,
      BSA NPs loaded with AS were prepared, and their drug-loading efficiency,
      morphology, and -release profiles were evaluated. Successful clinical development
      of AS-BSA-NPs may improve therapy and prevention of bronchospasm in patients with
      reversible obstructive airway disease, and thus provide a solid basis for
      expanding the role of NPs in the design of new drug-delivery systems.

PMID- 27695296
TI  - Nepalese patients' perceptions of treatment modalities for type 2 diabetes.
AB  - BACKGROUND: Perceptions and beliefs about treatment can influence patients'
      adherence to treatment regimens. Perceptions, in turn, are often shaped by
      patients' sociocultural context. Nepal and the Nepalese have unique sociocultural
      traditions and beliefs, and their perceptions of diabetes treatment remain
      largely unexplored. This study explored Nepalese participants' perceptions of
      diabetes treatment, and whether perceptions differed between the Nepalese living
      in Australia and Nepal. METHODS: Face-to-face qualitative interviews (n=48) were
      conducted with Nepalese participants with type 2 diabetes in Sydney and
      Kathmandu. All interviews were audio-recorded, transcribed verbatim, and
      thematically analyzed. RESULTS: Perceptions of diabetes treatment were similar
      among Nepalese participants in Australia and Nepal. There was a general
      reluctance to start oral antidiabetic medications and an even greater reluctance
      to commence parenteral (insulin) therapy. Participants preferred to try lifestyle
      modifications and alternative treatments such as herbs and "traditional"
      medicines, particularly as a first step. Unwillingness to take medications was
      primarily associated with the belief that, once started, these medications needed
      to be taken for life, and perceptions of long-term harms caused by such
      medications. Even when commenced on medication, participants were averse to any
      type of therapy escalation, for example, moving to insulin therapy. Insulin was
      perceived as the "last option" available for diabetes treatment. Most
      participants, however, did not find medication taking challenging once they had
      commenced treatment. CONCLUSION: Antidiabetic medications were perceived to be
      harmful and unstoppable once initiated. These perceptions significantly impacted
      participants' willingness to commence antidiabetic medications and therefore have
      the potential to adversely affect their medication-taking behavior. This study
      therefore highlights the need to explore the impact of these perceptions on
      participants' medication-taking behavior, and the need to address patients' views
      of "modern" (commonly prescribed) and "traditional" (natural) medications through
      information and education, to ensure increased understanding of how medications
      are used for diabetes management.

PMID- 27695297
TI  - Self-perception of knowledge and adherence reflecting the effectiveness of
      antiretroviral therapy.
AB  - OBJECTIVES: To evaluate which indirect method for assessing adherence best
      reflects highly active antiretroviral therapy (HAART) effectiveness and the
      factors related to adherence. METHOD: This descriptive, cross-sectional study was
      performed in 2012 at a reference center of the state of Sao Paulo. Self-report
      (simplified medication adherence questionnaire [SMAQ]) and drug refill parameters
      were compared to the viral load (clinical parameter of the effectiveness of
      pharmacotherapy [EP]) to evaluate the EP. The "Cuestionario para la Evaluacion de
      la Adhesion al Tratamiento Antiretroviral" (CEAT-VIH) was used to evaluate
      factors related to adherence and the EP and, complementarily, patient self
      perception of adherence was compared to the clinical parameter of the EP.
      RESULTS: Seventy-five patients were interviewed, 60 of whom were considered as
      adherent from the clinical parameter of the EP and ten were considered as
      adherent from all parameters. Patient self-perception about adherence was the
      instrument that best reflected the EP when compared to the standardized self
      report questionnaire (SMAQ) and drug refill parameter. The level of education and
      the level of knowledge on HAART were positively correlated to the EP.
      Forgetfulness, alcohol use, and lack of knowledge about the medications were the
      factors most frequently reported as a cause of nonadherence. CONCLUSION: A new
      parameter of patient self-perception of adherence, which is a noninvasive,
      inexpensive instrument, could be applied and assessed as easily as self-report
      (SMAQ) during monthly drug refill, since it allows monitoring adherence through
      pharmaceutical assistance. Therefore, patient adherence to HAART could be
      evaluated using self-perception (CEAT-VIH) and the viral load test.

PMID- 27695299
TI  - Medication adherence in patients with diabetes mellitus: does physician drug
      dispensing enhance quality of care? Evidence from a large health claims database
      in Switzerland.
AB  - BACKGROUND: The drug-dispensing channel is a scarcely explored determinant of
      medication adherence, which is considered as a key indicator for the quality of
      care among patients with diabetes mellitus. In this study, we investigated the
      difference in adherence between diabetes patients who obtained their medication
      directly from a prescribing physician (physician dispensing [PD]) or via a
      pharmacy. METHODS: A retrospective cohort study was conducted using a large
      health care claims database from 2011 to 2014. Patients with diabetes of all ages
      and receiving at least one oral antidiabetic drug (OAD) prescription were
      included. We calculated patients' individual adherence to OADs defined as the
      proportion of days covered (PDC), which was measured over 1 year after patient
      identification. Good adherence was defined as PDC >=80%. Multivariate logistic
      regression analysis was performed to assess the relationship between the PDC and
      the dispensing channel (PD, pharmacy). RESULTS: We identified a total of 10,430
      patients prescribed drugs by a dispensing physician and 16,292 patients receiving
      drugs from a pharmacy. Medication adherence was poor in both patient groups: ~40%
      of the study population attained good adherence to OADs. We found no significant
      impact of PD on the adherence level in diabetes patients. Covariates associated
      significantly with good adherence were older age groups, male sex, occurrence of
      comorbidity and combined diabetes drug therapy. CONCLUSION: In conclusion,
      adherence to antihyperglycemic medication is suboptimal among patients with
      diabetes. The results of this study provide evidence that the dispensing channel
      does not have an impact on adherence in Switzerland. Certainly, medication
      adherence needs to be improved in both supply settings. Physicians as well as
      pharmacists are encouraged to develop and implement useful tools to increase
      patients' adherence behavior.

PMID- 27695298
TI  - Patient considerations in cataract surgery - the role of combined therapy using
      phenylephrine and ketorolac.
AB  - Cataract, a degradation of the optical quality of the crystalline lens,
      progressive and age-related, is the leading cause of treatable blindness
      worldwide. Cataract surgery is the most common surgical procedure performed by
      ophthalmologists and is the only effective treatment for cataracts. Advances in
      the surgical techniques and better postoperative visual outcomes have
      progressively changed the primary concern of cataract surgery to become a
      procedure refined to yield the best possible refractive results. Sufficient
      mydriasis during cataract removal is critical to a successful surgical outcome.
      Poor pupil dilation can lead to serious sight-threatening complications that
      significantly increase the cost of surgery and decrease patients comfort.
      Mydriasis is obtained using anticholinergic and sympathomimetic drugs.
      Phenylephrine, an alpha1-adrenergic receptor agonist, can efficiently dilate the
      pupil when administered by intracameral injection. Additionally, nonsteroidal
      anti-inflammatory drugs (NSAIDs) like ketorolac, which inhibit the synthesis of
      prostaglandins, are used to decrease intraoperative miosis, control pain and
      inflammation associated with cataract surgery, and to prevent the development of
      cystoid macular edema following surgery. Recently, a new combination of
      phenylephrine and ketorolac (Omidria(r)) has been approved by United States Food
      and Drug Administration for use during cataract surgery to maintain
      intraoperative mydriasis, prevent miosis, and reduce postoperative pain and
      inflammation. Clinical trials have shown that this new combination is effective,
      combining the positive effects of both drugs with a good safety profile and
      patient tolerability. Moreover, recent reports suggest that this combination is
      also effective in patients with high risk of poor pupil dilation. In conclusion,
      cataract is a global problem that significantly affects patients' quality of
      life. However, they can be managed with a safe and minimally invasive surgery.
      Advances in surgical techniques and newer pharmacological agents such as the
      combination of phenylephrine and ketorolac, together with better intraocular
      lenses, have greatly improved visual outcomes and thus patients' expectations
      regarding visual recovery are also increasing.

PMID- 27695300
TI  - Factors associated with beta-blocker initiation and discontinuation in a
      population-based cohort of seniors newly diagnosed with heart failure.
AB  - PURPOSE: beta-Blockers (bisoprolol, carvedilol, and metoprolol) are the
      cornerstone of heart failure (HF) management. The incidence rate of beta-blocker
      initiation and discontinuation and their associated factors among seniors with a
      first HF diagnosis were assessed. METHODS: A population-based inception cohort
      study that included all individuals aged >=65 years with a first HF diagnosis in
      Quebec was conducted. beta-Blockers initiation among 91,131 patients who were not
      using beta-blockers at the time of HF diagnosis and discontinuation among those
      who initiated a beta-blocker after HF diagnosis were assessed. Stepwise Cox
      regression analyses were used to calculate hazard ratios (HR) and to identify
      factors associated with beta-blocker initiation and discontinuation. RESULTS:
      After HF diagnosis, 32,989 (36.2%) individuals initiated a beta-blocker. Of
      these, 15,408 (46.7%) discontinued their beta-blocker during the follow-up.
      Individuals more likely to initiate a beta-blocker were those diagnosed in a
      recent calendar year (2009: HR, 2.11; 95% confidence interval [CI], 2.00-2.23)
      and diagnosed by a cardiologist (HR, 1.38; 95% CI, 1.34-1.42). Individuals less
      likely to initiate were those aged >=90 years (HR, 0.65; 95% CI, 0.61-0.68) and
      those with chronic obstructive pulmonary disease (HR, 0.66; 95% CI, 0.64-0.68).
      Individuals more likely to discontinue were those with more than nine medical
      consultations (HR, 1.14; 95% CI, 1.10-1.18) and those with dementia (HR, 1.13;
      95% CI, 1.01-1.27). Individuals less likely to discontinue were those diagnosed
      in a recent calendar year (2009: HR 0.74; 95% CI, 0.65-0.82) and those exposed to
      another beta-blocker before HF diagnosis (HR, 0.88; 95% CI, 0.85-0.91).
      CONCLUSION: Quebec seniors seem to be underexposed to beta-blocker following HF
      diagnosis. Among those who initiate beta-blocker use, discontinuation is high.
      Better understanding of the underlying causes is needed to help target
      interventions to improve the management of HF.

PMID- 27695301
TI  - Patient-centered care interventions for the management of alcohol use disorders:
      a systematic review of randomized controlled trials.
AB  - ISSUES: Patient-centered care (PCC) is increasingly accepted as an integral
      component of good health care, including addiction medicine. However, its
      implementation has been controversial in people with alcohol use disorders.
      APPROACH: A systematic search strategy was devised to find completed randomized
      controlled trials enrolling adults (>18 years) with alcohol use disorders.
      Studies had to use a PCC approach such that they should have been individualized,
      respectful to the patients' own goals, and empowering. Studies until September
      2015 were searched using PubMed, Scopus, the Cochrane Library, PsychINFO, and Web
      of Knowledge. KEY FINDINGS: In total, 40 studies enrolling 16,020 patients met
      the inclusion criteria. Assessment revealed two main categories of study:
      psychosocial (n=35 based on motivational interviewing) and pharmacological (n=5
      based on an as needed dosing regimen). Psychosocial interventions were further
      classified according to the presence or absence of an active comparator. When no
      active comparator was present, studies were classified according to the number of
      sessions (>=1). Results from single sessions of motivational interviewing showed
      no clear benefit on alcohol consumption outcomes, with few studies indicating
      benefit of PCC versus control. Although the results for studies of multiple
      sessions of counseling were also mixed, many did show a significant benefit of
      the PCC intervention. By contrast, studies consistently demonstrated a benefit of
      pharmacologically supported PCC interventions, with most of the differences
      reaching statistical significance. IMPLICATIONS: PCC-based interventions may be
      beneficial for reducing alcohol consumption in people with alcohol use disorders.

PMID- 27695304
TI  - Invasive coronary angiography in patients with acute exacerbated COPD and
      elevated plasma troponin.
AB  - BACKGROUND: In acute exacerbation of COPD, increased plasma levels of cardiac
      troponin are frequent and associated with increased mortality. Thus, we aimed at
      prospectively determining the diagnostic value of coronary angiography in
      patients with exacerbated COPD and concomitantly elevated cardiac troponin.
      PATIENTS AND METHODS: A total of 88 patients (mean age 72.9+/-9.2 years, 56.8%
      male) hospitalized for acute exacerbation of COPD with elevated plasma troponin
      were included. All patients underwent coronary angiography within 72 hours after
      hospitalization. Complementary 12-lead electrocardiogram, transthoracic
      echocardiography, pulmonary function, and angiological testing were performed.
      RESULTS: Coronary angiography objectified the presence of ischemic heart disease
      (IHD) in 59 patients (67.0%), of whom 34 patients (38.6% of total study
      population) underwent percutaneous coronary intervention. Among these 34
      intervened patients, the vast majority (n=26, 76.5%) had no previously known IHD,
      whereas only eight out of 34 patients (23.5%) presented an IHD history. Patients
      requiring coronary intervention showed significantly reduced left ventricular
      ejection fraction (45.8%+/-13.1% vs 55.1%+/-13.3%, P=0.01) and a significantly
      more frequent electrocardiographic ST-segment depression (20.6% vs 7.4%, P=0.01).
      Neither additional laboratory parameters for inflammation and myocardial injury
      nor lung functional measurements differed significantly between the groups.
      CONCLUSION: Angiographically confirmed IHD that required revascularization
      occurred in 38.6% of exacerbated COPD patients with elevated cardiac troponin. In
      this considerable portion of patients, coronary angiography emerged to be of
      diagnostic and therapeutic value.

PMID- 27695303
TI  - Geriatric falls in the context of a hospital fall prevention program: delirium,
      low body mass index, and other risk factors.
AB  - BACKGROUND: Inpatient geriatric falls are a frequent complication of hospital
      care that results in significant morbidity and mortality. OBJECTIVE: Evaluate
      factors associated with falls in geriatric inpatients after implementation of the
      fall prevention program. METHODS: Prospective observational study comprised of
      788 consecutive patients aged 79.5+/-7.6 years ( [Formula: see text] +/- standard
      deviation) (66% women and 34% men) admitted to the subacute geriatric ward.
      Comprehensive geriatric assessment (including Mini-Mental State Examination,
      Barthel Index of Activities of Daily Living, and modified Get-up and Go Test) was
      performed. Confusion Assessment Method was used for diagnosis of delirium.
      Patients were categorized into low, moderate, or high fall risk groups after
      clinical and functional assessment. RESULTS: About 15.9%, 21.1%, and 63.1% of
      participants were classified into low, moderate, and high fall risk groups,
      respectively. Twenty-seven falls were recorded in 26 patients. Increased fall
      probability was associated with age >=76 years (P<0.001), body mass index (BMI)
      <23.5 (P=0.007), Mini-Mental State Examination <20 (P=0.004), Barthel Index <65
      (P=0.002), hemoglobin <7.69 mmol/L (P=0.017), serum protein <70 g/L (P=0.008),
      albumin <32 g/L (P=0.001), and calcium level <2.27 mmol/L. Four independent
      factors associated with fall risk were included in the multivariate logistic
      regression model: delirium (odds ratio [OR] =7.33; 95% confidence interval [95%
      CI] =2.76-19.49; P<0.001), history of falls (OR =2.55; 95% CI =1.05-6.19;
      P=0.039), age (OR =1.14; 95% CI =1.05-1.23; P=0.001), and BMI (OR =0.91; 95% CI
      =0.83-0.99; P=0.034). CONCLUSION: Delirium, history of falls, and advanced age
      seem to be the primary risk factors for geriatric falls in the context of a
      hospital fall prevention program. Higher BMI appears to be associated with
      protection against inpatient geriatric falls.

PMID- 27695305
TI  - Impact of current cough on health-related quality of life in patients with COPD.
AB  - BACKGROUND: Cough and sputum production are frequent in chronic obstructive
      pulmonary disease (COPD). The objective of this study was to examine the
      relationship between cough and sputum production and health-related quality of
      life in COPD. METHODS: A cross-sectional study was conducted in the French
      Initiatives COPD cohort and assessed cough and sputum production within the past
      7 days using the cough and sputum assessment questionnaire (CASA-Q), health
      related quality of life, spirometry, smoking status, dyspnea, exacerbations,
      anxiety and depression, and comorbidities. RESULTS: One hundred and seventy-eight
      stable COPD patients were included (age, 62 [56-69] years, 128 male, forced
      expiratory volume in 1 second [FEV1]: 57 [37-72] % predicted) (median [Q1-Q3]).
      In univariate analyses, health-related quality of life (Saint George's
      respiratory questionnaire total score) was associated with each CASA-Q domain and
      with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety.
      All four domains introduced separately were independently associated with health
      related quality of life. When introduced together in multivariate analyses, only
      the cough impact domain remained independently associated with health-related
      quality of life (R2=0.60). With chronic bronchitis (standard definition) instead
      of the CASA-Q, the R2 was lower (R2=0.54). CONCLUSION: This study provides
      evidence that current cough in the previous 7 days is an important determinant of
      health-related quality of life impairment in stable COPD patients.

PMID- 27695306
TI  - Differences in physical activity according to mMRC grade in patients with COPD.
AB  - BACKGROUND: Physical activity (PA) is impaired from the early stages of COPD, is
      associated with a worsening of disease prognosis, and causes COPD patients to
      restrict their daily activities in order to avoid breathlessness. The development
      of a simple tool to estimate physical activity level (PAL) could be useful for
      the management of COPD. OBJECTIVES: We investigated the differences in PA
      according to the modified Medical Research Council (mMRC) grade in patients with
      COPD. METHODS: A cross-sectional study was performed on stable outpatients with
      COPD. PA was measured for 2 weeks using a triaxial accelerometer, and dyspnea
      grade was evaluated in all patients using the mMRC scale. RESULTS: Ninety-eight
      patients were recruited. Significant differences in PA duration were observed at
      all intensities according to the mMRC grade. Despite treatment with controller
      medications, 59.2% of COPD patients had low PAL, which was <1.5 metabolic
      equivalents multiplied by hour per day. COPD patients with an mMRC grade >=2,
      which was the most balanced cutoff point in the receiver operating characteristic
      curve, showed a higher reduction rate of PAL (80.0% at mMRC grade 2, 71.4% at
      mMRC grade 3, and 100% at mMRC grade 4). CONCLUSION: PA differed according to the
      mMRC grade, and mMRC grade >=2 could predict a low PAL. Therefore, assessment of
      breathlessness by the mMRC questionnaire would be useful to stratify the risks of
      reduced PA in COPD.

PMID- 27695302
TI  - Survey of Genes Involved in Biosynthesis, Transport, and Signaling of
      Phytohormones with Focus on Solanum lycopersicum.
AB  - Phytohormones control the development and growth of plants, as well as their
      response to biotic and abiotic stress. The seven most well-studied phytohormone
      classes defined today are as follows: auxins, ethylene, cytokinin, abscisic acid,
      jasmonic acid, gibberellins, and brassinosteroids. The basic principle of hormone
      regulation is conserved in all plants, but recent results suggest adaptations of
      synthesis, transport, or signaling pathways to the architecture and growth
      environment of different plant species. Thus, we aimed to define the extent to
      which information from the model plant Arabidopsis thaliana is transferable to
      other plants such as Solanum lycopersicum. We extracted the co-orthologues of
      genes coding for major pathway enzymes in A. thaliana from the translated genomes
      of 12 species from the clade Viridiplantae. Based on predicted domain
      architecture and localization of the identified proteins from all 13 species, we
      inspected the conservation of phytohormone pathways. The comparison was
      complemented by expression analysis of (co-) orthologous genes in S.
      lycopersicum. Altogether, this information allowed the assignment of putative
      functional equivalents between A. thaliana and S. lycopersicum but also pointed
      to some variations between the pathways in eudicots, monocots, mosses, and green
      algae. These results provide first insights into the conservation of the various
      phytohormone pathways between the model system A. thaliana and crop plants such
      as tomato. We conclude that orthologue prediction in combination with analysis of
      functional domain architecture and intracellular localization and expression
      studies are sufficient tools to transfer information from model plants to other
      plant species. Our results support the notion that hormone synthesis, transport,
      and response for most part of the pathways are conserved, and species-specific
      variations can be found.

PMID- 27695307
TI  - Noninvasive mechanical ventilation on the ward for severe COPD: still unresolved
      question of balance among safety and drawbacks?

PMID- 27695309
TI  - Correlates of disease-specific knowledge in Chinese patients with COPD.
AB  - BACKGROUND: This study aimed to determine the associations of various
      sociodemographic factors with the level of disease-specific knowledge among Hong
      Kong Chinese patients with COPD. METHODS: A cross-sectional survey of 100 Chinese
      adults with COPD recruited from outpatient clinics was conducted from September
      2009 to September 2010. Data on the knowledge specific to COPD and patients'
      sociodemographics were collected from face-to-face interviews. Primary outcome of
      disease-specific knowledge was measured using 65-item Bristol COPD Knowledge
      Questionnaire (BCKQ), summing up the 65 items as the BCKQ overall score.
      Associations of sociodemographic factors with the BCKQ overall score were
      evaluated using the linear regression model. RESULTS: The mean BCKQ overall score
      of our patients was 41.01 (SD: 10.64). The knowledge in topics of "Smoking" and
      "Phlegm" achieved the first (3.97, SD: 0.82) and second (3.91, SD: 1.17) highest
      mean scores, respectively, while the topic of "Oral steroids" returned the lowest
      mean score of 1.89 (SD: 1.64). The BCKQ overall score progressively declined
      (P<0.001) with increase in education level, with the highest BCKQ overall score
      of 46.71 at no formal education among all subgroups. Compared to nondrinkers,
      current drinkers were associated with lower total BCKQ score. CONCLUSION: We
      found that among COPD patients in outpatient clinics, impairments in the level of
      COPD knowledge were evident in patients who were current drinkers or had higher
      level of education.

PMID- 27695308
TI  - Health-related quality of life in current smokers with COPD: factors associated
      with current smoking and new insights into sex differences.
AB  - Findings from studies that examined the association between health-related
      quality of life (HRQOL) and smoking status among COPD patients have been mixed.
      Moreover, factors associated with current smoking in COPD patients and
      differences by sex have not been fully elucidated. Data from the 2011 and 2012
      Behavioral Risk Factor Surveillance System was used in this study. Four HRQOL
      indicators were examined in this study: general health, physical health, mental
      health, and activity limitations. General health was dichotomized into two
      groups: "excellent/very good/good" and "fair/poor", and the other three HRQOL
      indicators were dichotomized into <14 (infrequent) and >=14 (frequent) unhealthy
      days in the past 30 days. To examine HRQOL indicators in association with current
      versus former smoking and identify factors associated with current smoking,
      logistic regression models were used. Sex differences were explored. In COPD
      patients, current smokers compared to former smokers had significantly poor HRQOL
      on all subdomains: "fair/poor" general health (adjusted odds ratio [AOR]: 1.2
      [95% confidence interval {CI}: 1.1-1.5]); poor physical health (AOR: 1.3 [CI: 1.1
      1.5]); poor mental health (AOR: 1.8 [CI: 1.4-2.2]); and poor activity limitations
      (AOR: 1.5 [CI: 1.3-1.9]). HRQOL subdomains affected by current smoking differed
      by sex except activity limitations. General health (AOR: 1.5 [CI: 1.1-2.0]) and
      activity limitations (AOR: 1.6 [95% CI: 1.2-2.2]) in males and physical health
      (AOR: 1.3 [CI: 1.0-1.6]), mental health (AOR: 2.1 [CI: 1.7-2.6]), and activity
      limitations (AOR: 1.5 [CI: 1.2-1.9]) in females were significantly impaired due
      to current smoking. Factors associated with current smoking differed by sex
      except being unmarried and having less than a college degree, which were
      associated with current smoking in both males and females. These findings have
      important implications for health care providers in designing more effective
      interventions which tailor to and target specific subgroups for smoking
      cessation.

PMID- 27695310
TI  - Prevalence of comorbidities according to predominant phenotype and severity of
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: In addition to lung involvement, several other diseases and syndromes
      coexist in patients with chronic obstructive pulmonary disease (COPD). Our
      purpose was to investigate the prevalence of idiopathic arterial hypertension
      (IAH), ischemic heart disease, heart failure, peripheral vascular disease (PVD),
      diabetes, osteoporosis, and anxious depressive syndrome in a clinical setting of
      COPD outpatients whose phenotypes (predominant airway disease and predominant
      emphysema) and severity (mild and severe diseases) were determined by clinical
      and functional parameters. METHODS: A total of 412 outpatients with COPD were
      assigned either a predominant airway disease or a predominant emphysema phenotype
      of mild or severe degree according to predictive models based on pulmonary
      functions (forced expiratory volume in 1 second/vital capacity; total lung
      capacity %; functional residual capacity %; and diffusing capacity of lung for
      carbon monoxide %) and sputum characteristics. Comorbidities were assessed by
      objective medical records. RESULTS: Eighty-four percent of patients suffered from
      at least one comorbidity and 75% from at least one cardiovascular comorbidity,
      with IAH and PVD being the most prevalent ones (62% and 28%, respectively). IAH
      prevailed significantly in predominant airway disease, osteoporosis prevailed
      significantly in predominant emphysema, and ischemic heart disease and PVD
      prevailed in mild COPD. All cardiovascular comorbidities prevailed significantly
      in predominant airway phenotype of COPD and mild COPD severity. CONCLUSION:
      Specific comorbidities prevail in different phenotypes of COPD; this fact may be
      relevant to identify patients at risk for specific, phenotype-related
      comorbidities. The highest prevalence of comorbidities in patients with mild
      disease indicates that these patients should be investigated for coexisting
      diseases or syndromes even in the less severe, pauci-symptomatic stages of COPD.
      The simple method employed to phenotype and score COPD allows these results to be
      translated easily into daily clinical practice.

PMID- 27695311
TI  - Systolic time intervals combined with Valsalva maneuver for the diagnosis of left
      ventricular dysfunction in COPD exacerbations.
AB  - BACKGROUND: The goal of this study was to determine the value of systolic time
      intervals and their change during Valsalva maneuver (VM) in the diagnosis of left
      ventricular dysfunction (LVD) in patients with acute exacerbation of chronic
      obstructive pulmonary disease (AECOPD). METHODS: We included 166 patients
      admitted to the emergency department for AECOPD. Measurement of systolic time
      intervals included electromechanical activation time (EMAT), left ventricular
      ejection time (LVET), and EMAT/LVET ratio. These were performed at baseline and
      during the first strain phase of the VM using a computerized
      phonoelectrocardiographic method. The diagnosis of LVD was determined on the
      basis of clinical examination, echocardiography, and brain natriuretic peptide.
      The values of systolic time intervals were compared between patients with and
      without LVD; their diagnostic performance was assessed using the area under
      receiver operating characteristic (ROC) curve. RESULTS: Patients with LVD (n=95)
      had a significantly higher EMAT and lower LVET and EMAT/LVET ratio compared to
      patients without LVD (n=71); the area under ROC curve was 0.79, 0.88, and 0.90,
      respectively, for EMAT, LVET, and EMAT/LVET ratio. All baseline systolic time
      intervals changed significantly during VM in patients without LVD but they did
      not change in patients with LVD. The area under ROC curve increased to 0.84 and
      0.93, respectively, for EMAT and EMAT/LVET ratio but did not change for LVET.
      CONCLUSION: Simple and noninvasive measurements of systolic time intervals
      combined with VM could be helpful to detect or rule out LVD in patients admitted
      to the emergency room for COPD excacerbation. The EMAT/LVET ratio seems to have
      the best diagnostic value.

PMID- 27695313
TI  - The use of high-flow nasal oxygen in COPD patients.

PMID- 27695312
TI  - Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers
      with and without COPD.
AB  - BACKGROUND: Long-term exposure to tobacco smoke causes local inflammation in the
      airways that involves not only innate immune cells, including NK cells, but also
      adaptive immune cells such as cytotoxic (CD8+) and helper (CD4+) T-cells. We have
      previously demonstrated that long-term tobacco smoking increases extracellular
      concentration of the CD4+-recruiting cytokine interleukin (IL)-16 locally in the
      airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the
      systemic level and that this effect involves oxygen free radicals (OFR). METHODS:
      We quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK
      cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from
      long-term tobacco smokers with and without chronic obstructive pulmonary disease
      (COPD) and in never-smokers. NK cells from healthy blood donors were stimulated
      with water-soluble tobacco smoke components (cigarette smoke extract) with or
      without an OFR scavenger (glutathione) in vitro and followed by quantification of
      IL-16 protein. RESULTS: The extracellular concentrations of IL-16 protein in
      blood did not display any substantial differences between groups. Notably,
      intracellular IL-16 protein was detected in all types of blood leukocytes. All
      long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective
      of COPD status. Further, both NK and CD4+ T-cell concentrations displayed a
      negative correlation with pack-years. Moreover, cigarette smoke extract caused
      release of IL-16 protein from NK cells in vitro, and this was not affected by
      glutathione, in contrast to the decrease in intracellular IL-16, which was
      prevented by this drug. CONCLUSION: Long-term exposure to tobacco smoke does not
      markedly alter extracellular concentrations of IL-16 protein in blood. However,
      it does decrease the intracellular IL-16 concentrations in blood NK cells, the
      latter effect involving OFR. Thus, long-term tobacco smoking exerts an impact at
      the systemic level that involves NK cells; innate immune cells that are critical
      for host defense against viruses and tumors - conditions that are overrepresented
      among smokers.

PMID- 27695314
TI  - Myocardial performance index correlates with the BODE index and affects quality
      of life in COPD patients.
AB  - BACKGROUND AND OBJECTIVE: COPD, a systemic illness associated with the impairment
      of different organs, affects patient prognosis and quality of life. The aim of
      this study was to evaluate the association between right ventricle (RV) function,
      the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity)
      index (a multifunctional scale for the assessment of mortality risk), and quality
      of life in patients with COPD. METHODS: A cross-sectional study was carried out
      in 107 outpatients presenting with stable COPD who underwent clinical assessment,
      spirometry, arterial blood gas analyses, a 6-minute walk test,
      electrocardiography, and echocardiogram and who responded to the Saint George's
      Respiratory Questionnaire (SGRQ). RESULTS: Among the study subjects, 53% (57/107)
      were males, and the mean age was 65.26+/-8.81 years. A positive correlation was
      observed between RV dysfunction measured by the myocardial performance index
      using tissue Doppler (MPIt) and the BODE index, even after adjustment for age and
      partial pressure of oxygen (r2=0.47; P<0.01). Patients with alterations in the
      MPIt had worse quality of life, and a statistically significant difference was
      found for different domains of the SGRQ. Patients with a normal MPIt had a mean
      total score of 46.2+/-18.6, whereas for those with MPIt alterations, the mean
      total score was 61.6+/-14.2 (P=0.005). These patients had a 1.49-fold increased
      risk of exhibiting SGRQ total score above the upper limit of the 95% CI (P=0.01).
      CONCLUSION: The findings of this study suggest that RV dysfunction as measured by
      the MPIt was associated with impairment in quality of life and a worse BODE index
      in COPD patients, irrespective of age and hypoxemia status.

PMID- 27695315
TI  - Breakdown of lung framework and an increase in pores of Kohn as initial events of
      emphysema and a cause of reduction in diffusing capacity.
AB  - PURPOSE: Pulmonary emphysema is the pathological prototype of chronic obstructive
      pulmonary disease and is also associated with other lung diseases. We considered
      that observation with different approaches may provide new insights for the
      pathogenesis of emphysema. PATIENTS AND METHODS: We reviewed tissue blocks of the
      lungs of 25 cases with/without emphysema and applied a three-dimensional
      observation method to the blocks. Based on the three-dimensional characteristics
      of the alveolar structure, we considered one face of the alveolar polyhedron as a
      structural unit of alveoli and called it a framework unit (FU). We categorized
      FUs based on their morphological characteristics and counted their number to
      evaluate the destructive changes in alveoli. We also evaluated the number and the
      area of pores of Kohn in FUs. We performed linear regression analysis to estimate
      the effect of these data on pulmonary function tests. RESULTS: In multivariable
      regression analysis, a decrease in the number of FUs without an alveolar wall led
      to a significant decrease in the diffusing capacity of the lung for carbon
      monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of
      pores of Kohn had a significant effect on an increase in residual capacity.
      CONCLUSION: A breakdown in the lung framework and an increase in pores of Kohn
      are associated with a decrease in DLCO and DLCO per unit alveolar volume
      with/without emphysema.

PMID- 27695317
TI  - Preference for different relaxation techniques by COPD patients: comparison
      between six techniques.
AB  - BACKGROUND: A review of the effectiveness of relaxation techniques for chronic
      obstructive pulmonary disease patients has shown inconsistent results, but
      studies have varied in terms of technique and outcome measures. AIM: To determine
      patient preference for different relaxation techniques. METHODS: Chronic
      obstructive pulmonary disease patients were presented with six techniques via a
      DVD and asked to rate the techniques in terms of effectiveness, rank in order of
      likely use, and comment. RESULTS: Patients differed in the technique preferred
      and reason for that preference, but the most commonly preferred technique both
      for effectiveness and ease of use was "thinking of a nice place" followed by
      progressive relaxation and counting. Familiarity and ease of activity were
      commonly given reasons for preference. CONCLUSION: Rather than providing patients
      with a single technique that they might find difficult to implement, these
      results suggest that it would be better to give a choice. "Thinking of a nice
      place" is a popular but under-investigated technique.

PMID- 27695316
TI  - What else should we know about experiencing COPD? A narrative review in search of
      patients' psychological burden alleviation.
AB  - The present paper is a narrative review focusing on the psychological impact,
      identification of protective factors, and interventions minimizing the
      psychological burdens of chronic obstructive pulmonary disease (COPD). The
      research reviews studies on neurocognitive functions, personality, emotional
      problems, and health-related quality of life. This is done with regard to
      resources as well as activities enabling or enhancing a patient's adaptation.
      PubMed and PsychArticles databases were searched for relevant medical (eg, CODP,
      emphysema), psychopathology (eg, depression), and psychological (eg, personality)
      keywords, followed by hand search. After application of the inclusion and
      exclusion criteria, the search resulted in 82 articles and book chapters. The
      choice was based on evidence accepted by evidence-based medicine, although at
      different levels of strength. Psychological experiencing of COPD appears to be
      very unequally represented with scientific research on emotional problems and
      functioning decrease significantly outnumbering those addressing resources or
      effective interventions. As our initial literature search called for an urgent
      need for further exploration, we have carefully pointed out numerous areas where
      the knowledge on how to protect or restore psychological well-being among COPD
      patients should be broadened.

PMID- 27695318
TI  - Folate-conjugated boron nitride nanospheres for targeted delivery of anticancer
      drugs.
AB  - With its unique physical and chemical properties and structural similarity to
      carbon, boron nitride (BN) has attracted considerable attention and found many
      applications. Biomedical applications of BN have recently started to emerge,
      raising great hopes in drug and gene delivery. Here, we developed a targeted
      anticancer drug delivery system based on folate-conjugated BN nanospheres (BNNS)
      with receptor-mediated targeting. Folic acid (FA) was successfully grafted onto
      BNNS via esterification reaction. In vitro cytotoxicity assay showed that BNNS-FA
      complexes were non-toxic to HeLa cells up to a concentration of 100 MUg/mL. Then,
      doxorubicin hydrochloride (DOX), a commonly used anticancer drug, was loaded onto
      BNNS-FA complexes. BNNS-FA/DOX complexes were stable at pH 7.4 but effectively
      released DOX at pH 5.0, which exhibited a pH sensitive and sustained release
      pattern. BNNS-FA/DOX complexes could be recognized and specifically internalized
      by HeLa cells via FA receptor-mediated endocytosis. BNNS-FA/DOX complexes
      exhibited greater cytotoxicity to HeLa cells than free DOX and BNNS/DOX complexes
      due to the increased cellular uptake of DOX mediated by the FA receptor.
      Therefore, BNNS-FA complexes had strong potential for targeted cancer therapy.

PMID- 27695319
TI  - Synthesis of composite magnetic nanoparticles Fe3O4 with alendronate for
      osteoporosis treatment.
AB  - Osteoporosis is a result of imbalance between bone formation by osteoblasts and
      resorption by osteoclasts (OCs). In the present study, we investigated the
      potential of limiting the aggravation of osteoporosis by reducing the activity of
      OCs through thermolysis. The proposed method is to synthesize bisphosphonate
      (Bis)-conjugated iron (II, III) oxide (Fe3O4) nanoparticles and incorporate them
      into OCs. The cells should be subsequently exposed to radiofrequency (RF) to
      induce thermolysis. In this study, particles of Fe3O4 were first synthesized by
      chemical co-precipitation and then coated with dextran (Dex). The Dex/Fe3O4
      particles were then conjugated with Bis to form Bis/Dex/Fe3O4. Transmission
      electron microscopy revealed that the average diameter of the Bis/Dex/Fe3O4
      particles was ~20 nm. All three kinds of nanoparticles were found to have cubic
      inverse spinel structure of Fe3O4 by the X-ray diffraction analysis. Fourier
      transform infrared spectroscopy confirmed that the Dex/Fe3O4 and Bis/Dex/Fe3O4
      nanoparticles possessed their respective Dex and Bis functional groups, while a
      superconducting quantum interference device magnetometer measured the magnetic
      moment to be 24.5 emu. In addition, the Bis/Dex/Fe3O4 nanoparticles were fully
      dispersed in double-distilled water. Osteoblasts and OCs were individually
      cultured with the nanoparticles, and an MTT assay revealed that they were non
      cytotoxic. An RF system (42 kHz and 450 A) was used to raise the temperature of
      the nanoparticles for 20 minutes, and the thermal effect was found to be
      sufficient to destroy OCs. Furthermore, in vivo studies verified that
      nanoparticles were indeed magnetic resonance imaging contrast agents and that
      they accumulated after being injected into the body of rats. In conclusion, we
      developed a water-dispersible magnetic nanoparticle that had RF-induced
      thermogenic properties, and the results indicated that the Bis/Dex/Fe3O4
      nanoparticle had the potential for controlling osteoporosis.

PMID- 27695320
TI  - The effect of neutral-surface iron oxide nanoparticles on cellular uptake and
      signaling pathways.
AB  - In recent years, iron oxide nanoparticles (IONPs) have been applied widely to
      biomedical fields. However, the relationship between the physicochemical
      properties of IONPs and their biological behavior is not fully understood yet. We
      prepared 3-methacryloxypropyltrimethoxysilane (MPS)-coated IONPs, which have a
      neutral hydrophobic surface, and compared their biological behavior to that of
      Resovist (ferucarbotran), a commercialized IONP formulation modified with
      carboxymethyl dextran. The rate of MPS-IONP uptake by human aortic endothelial
      cells (HAoECs) was higher than ferucarbotran uptake, indicating that the neutral
      hydrophobic nature of MPS-IONPs allowed them to be absorbed more readily through
      the plasma membrane. However, the signaling pathways activated by MPS-IONPs and
      ferucarbotran were comparable, suggesting that surface charge is not a key factor
      for inducing changes in HAoECs. In vivo fate analysis showed that MPS-IONPs
      accumulated for longer periods in tissues than hydrophilic ferucarbotran. These
      findings could enlarge our understanding of NP behavior for advanced applications
      in the biomedical field.

PMID- 27695321
TI  - Effective combination treatment of lung cancer cells by single vehicular delivery
      of siRNA and different anticancer drugs.
AB  - In recent years, lung cancer has become one of the fastest growing cancers in the
      world. Thus, the development of efficient combination therapy to treat lung
      cancer has attracted significant attention in the cancer therapy field. In this
      article, we developed a single vehicle drug delivery system, based on quantum dot
      (QD) nanoparticles, to deliver small interfering RNA (siRNA; target Bcl-2) and
      different anticancer drugs (carboplatin, paclitaxel, and doxorubicin)
      simultaneously for treating A549 lung cancer cells efficiently by combination
      therapy. The QD nanoparticles were conjugated with l-arginine (l-Arg) and
      different kinds of hydroxypropyl-cyclodextrins (HP-alpha-CDs, HP-beta-CDs, and HP
      gamma-CDs) on the surface to form the delivery nanocarriers (QD nanocarriers).
      They were able to not only bind and transport the siRNA through electrostatic
      interactions with l-Arg residues but also accommodate various disparate
      anticancer drugs using different HP-CD modifications. Compared with free drug
      treatments, the use of QD nanocarriers to deliver Bcl-2 siRNA and different
      anticancer drugs simultaneously exerted a threefold to fourfold increase in
      cytotoxicity in A549 cells, which greatly improved the treatment efficacy through
      combined action. Furthermore, the QD nanocarriers could be used as a probe for
      real-time imaging of the drug delivery and release because of their strong
      fluorescence properties. These findings indicate that multifunctional QD
      nanocarriers hold great promise as a powerful tool for combination therapy for
      lung cancer.

PMID- 27695322
TI  - Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory
      responses in primary human monocytes.
AB  - Co-stimulation of the immune system to more than one agent concomitantly is very
      common in real life, and considering the increasing use of engineered
      nanoparticles and nanomaterials, it is highly relevant to assess the ability of
      these materials to modulate key innate immune responses, which has not yet been
      studied in detail. We investigated the immunomodulatory effects of 10 nm and 30
      nm iron oxide nanoparticles (IONPs) on primary human monocytes in the presence
      and absence of Toll-like receptor 4 agonist lipopolysaccharide (LPS). Prior to
      the cell studies, we characterized the physicochemical properties of the
      nanoparticles in cell culture medium and ensured that the nanoparticles were free
      from biological contamination. Cellular uptake of the IONPs in monocytes was
      assessed using transmission electron microscopy. Using enzyme-linked
      immunosorbent assay, we found that the IONPs per se did not induce the production
      of proinflammatory cytokines tumor necrosis factor-alpha, interleukin-6, and
      interleukin-1beta. However, the IONPs had the ability to suppress LPS-induced
      nuclear factor kappa B activation and production of proinflammatory cytokines in
      primary human monocytes in an LPS and a particle dose-dependent manner. Using
      confocal microscopy and fluorescently labeled LPS, we showed that the effects
      correlated with impaired LPS internalization by monocytes in the presence of
      IONPs, which could be partly explained by LPS adsorption onto the nanoparticle
      surface. Additionally, the results from particle pretreatment experiments
      indicate that other cellular mechanisms might also play a role in the observed
      effects, which warrants further studies to elucidate the additional mechanisms
      underlying the capacity of IONPs to alter the reactivity of monocytes to LPS and
      to mount an appropriate cellular response.

PMID- 27695324
TI  - Metal oxide nanoparticles interact with immune cells and activate different
      cellular responses.
AB  - Besides cell death, nanoparticles (Nps) can induce other cellular responses such
      as inflammation. The potential immune response mediated by the exposure of human
      lymphoid cells to metal oxide Nps (moNps) was characterized using four different
      moNps (CeO2, TiO2, Al2O3, and ZnO) to study the three most relevant mitogen
      activated protein kinase subfamilies and the nuclear factor kappa-light-chain
      enhancer of the activated B-cell inhibitor, IkappaBalpha, as well as the
      expression of several genes by immune cells incubated with these Nps. The moNps
      activated different signaling pathways and altered the gene expression in human
      lymphocyte cells. The ZnO Nps were the most active and the release of Zn2+ ions
      was the main mechanism of toxicity. CeO2 Nps induced the smallest changes in gene
      expression and in the IkappaBalpha protein. The effects of the particles were
      strongly dependent on the type and concentration of the Nps and on the cell
      activation status prior to Np exposure.

PMID- 27695323
TI  - Dual-function synthetic peptide derived from BMP4 for highly efficient tumor
      targeting and antiangiogenesis.
AB  - Angiogenesis plays a critical role in the growth and metastasis of cancer, and
      growth factors released from cancer promote blood-vessel formation in the tumor
      microenvironment. The angiogenesis is accelerated via interactions of growth
      factors with the high-affinity receptors on cancer cells. In particular, heparan
      sulfate proteoglycans (HSPGs) on the surface of cancer cells have been shown to
      be important in many aspects of determining a tumor's phenotype and development.
      Specifically, the regulation of the interactions between HSPGs and growth factors
      results in changes in tumor progression. A peptide with heparin-binding (HBP)
      activity has been developed and synthesized to inhibit tumor growth via the
      prevention of angiogenesis. We hypothesized that HBP could inhibit the
      interaction of growth factors and HSPGs on the surface of cancer cells, decrease
      paracrine signaling in endothelial cells (ECs), and finally decrease angiogenesis
      in the tumor microenvironment. In this study, we found that HBP had
      antiangiogenic effects in vitro and in vivo. The conditioned media obtained from
      a breast cancer cell line treated with HBP were used to culture human umbilical
      vein ECs (HUVECs) to evaluate the antiangiogenic effect of HBP on ECs. HBP
      effectively inhibited the migration, invasion, and tube formation of HUVECs in
      vitro. In addition, the expressions of angiogenesis-mediating factors, including
      ERK, FAK, and Akt, were considerably decreased. HBP also decreased the levels of
      invasive factors, including MMP2 and MMP9, secreted by the HUVECs. We
      demonstrated significant suppression of tumor growth in a breast cancer xenograft
      model and enhanced distribution of HBP at the site of tumors. Taken together, our
      results show that HBP has antiangiogenic effects on ECs, and suggest that it may
      serve as a potential antitumor agent through control of the tumor
      microenvironment.

PMID- 27695326
TI  - Comparative study of proteasome inhibitory, synergistic antibacterial,
      synergistic anticandidal, and antioxidant activities of gold nanoparticles
      biosynthesized using fruit waste materials.
AB  - The aim of this study was to compare the biological synthesis of gold
      nanoparticles (AuNPs) generated using the aqueous extracts of outer oriental
      melon peel (OMP) and peach. The synthesized OMP-AuNPs and peach extract (PE)
      AuNPs were characterized by ultraviolet-visible spectroscopy, field emission
      scanning electron microscopy, energy dispersive X-ray analysis, X-ray powder
      diffraction, Fourier transform infrared spectroscopy, and thermogravimetric
      analysis. The surface plasmon resonance spectra were obtained at 545 nm and 540
      nm for OMP-AuNPs and PE-AuNPs, respectively. The estimated absolute crystallite
      size of the synthesized AuNPs was calculated to be 78.11 nm for OMP-AuNPs and
      39.90 nm for PE-AuNPs based on the Scherer equation of the X-ray powder
      diffraction peaks. Fourier transform infrared spectroscopy results revealed the
      involvement of bioactive compounds present in OMP and peach extracts in the
      synthesis and stabilization of synthesized AuNPs. Both the OMP-AuNPs and PE-AuNPs
      showed a strong antibacterial synergistic activity when combined with kanamycin
      (9.38-20.45 mm inhibition zones) and rifampicin (9.52-25.23 mm inhibition zones),
      and they also exerted a strong synergistic anticandidal activity (10.09-15.47 mm
      inhibition zones) when combined with amphotericin B against five pathogenic
      Candida species. Both the OMP-AuNPs and PE-AuNPs exhibited a strong antioxidant
      potential in terms of 1,1-diphenyl-2-picrylhydraxyl radical scavenging, nitric
      oxide scavenging, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical
      scavenging, and a reducing power, along with a strong proteasome inhibitory
      potential that could be useful in cancer drug delivery and cancer treatments. The
      PE-AuNPs showed comparatively higher activity than OMP-AuNPs, which could be
      attributed to the presence of rich bioactive compounds in the PE that acted as
      reducing and capping agents in the synthesis of PE-AuNPs. Overall, the results of
      the current investigation highlighted a novel green technology for the synthesis
      of AuNPs using food waste materials and their potential applications in the
      biomedical, pharmaceutical, and cosmetic industries.

PMID- 27695325
TI  - Surface biofunctionalized CdS and ZnS quantum dot nanoconjugates for nanomedicine
      and oncology: to be or not to be nanotoxic?
AB  - Herein, for the first time, we demonstrated that novel biofunctionalized
      semiconductor nanomaterials made of Cd-containing fluorescent quantum dot
      nanoconjugates with the surface capped by an aminopolysaccharide are not
      biologically safe for clinical applications. Conversely, the ZnS-based
      nanoconjugates proved to be noncytotoxic, considering all the parameters
      investigated. The results of in vitro cytotoxicity were remarkably dependent on
      the chemical composition of quantum dot (CdS or ZnS), the nature of the cell
      (human cancerous and embryonic types), and the concentration and time period of
      exposure to these nanomaterials, caused by the effects of Cd2+ on the complex
      nanotoxicity pathways involved in cellular uptake. Unexpectedly, no decisive
      evidence of nanotoxicity of CdS and ZnS conjugates was observed in vivo using
      intravenous injections in BALB/c mice for 30 days, with minor localized
      fluorescence detected in liver tissue specimens. Therefore, these results proved
      that CdS nanoconjugates could pose an excessive threat for clinical applications
      due to unpredicted and uncorrelated in vitro and in vivo responses caused by
      highly toxic cadmium ions at biointerfaces. On the contrary, ZnS nanoconjugates
      proved that the "safe by design" concept used in this research (ie, biocompatible
      core-shell nanostructures) could benefit a plethora of applications in
      nanomedicine and oncology.

PMID- 27695327
TI  - Fabrication of gelatin methacrylate/nanohydroxyapatite microgel arrays for
      periodontal tissue regeneration.
AB  - INTRODUCTION: Periodontitis is a chronic infectious disease and is the major
      cause of tooth loss and other oral health issues around the world. Periodontal
      tissue regeneration has therefore always been the ultimate goal of dentists and
      researchers. Existing fabrication methods mainly focused on a top-down tissue
      engineering strategy in which several drawbacks remain, including low throughput
      and limited diffusion properties resulting from a large sample size. Gelatin
      methacrylate (GelMA) is a kind of photocrosslinkable and biocompatible hydrogel,
      with the capacities of enabling cell encapsulation and regeneration of functional
      tissues. Here, we developed a novel method to fabricate GelMA/nanohydroxylapatite
      (nHA) microgel arrays using a photocrosslinkable strategy. The viability,
      proliferation, and osteogenic differentiation and in vivo osteogenesis of human
      periodontal ligament stem cells (hPDLSCs) encapsulated in microgels were
      evaluated. The results suggested that such microgels provide great potential for
      periodontal tissue repair and regeneration. METHODS: Microgel arrays were
      fabricated by blending different weight ratios of GelMA and nHA. hPDLSCs were
      encapsulated in GelMA/nHA microgels of various ratios for a systematic evaluation
      of cell viability, proliferation, and osteogenic differentiation. In vivo
      osteogenesis in nude mice was also studied. RESULTS: The GelMA/nHA microgels
      exhibited appropriate microarchitecture, mechanical strength, and surface
      roughness, thus enabling cell adhesion and proliferation. Additionally, the
      GelMA/nHA microgels (10%/2% w/v) enhanced the osteogenic differentiation of
      hPDLSCs by elevating the expression levels of osteogenic biomarker genes, such as
      ALP, BSP, OCN, and RUNX2. In vivo ectopic transplantation results showed that
      GelMA/nHA microgels (10%/2% w/v) increased mineralized tissue formation with
      abundant vascularization, compared with the 1%, 3%, and the pure GelMA group.
      CONCLUSION: The GelMA/nHA microgels (10%/2% w/v) facilitated hPDLSCs viability,
      proliferation, and osteogenic differentiation in vitro and further promoted new
      bone formation in vivo, suggesting that the GelMA/nHA microgels (10%/2% w/v)
      provide great potential for periodontal tissue regeneration.

PMID- 27695329
TI  - Monte Carlo and analytic simulations in nanoparticle-enhanced radiation therapy.
AB  - Analytical and Monte Carlo simulations have been used to predict dose enhancement
      factors in nanoparticle-enhanced X-ray radiation therapy. Both simulations
      predict an increase in dose enhancement in the presence of nanoparticles, but the
      two methods predict different levels of enhancement over the studied energy,
      nanoparticle materials, and concentration regime for several reasons. The Monte
      Carlo simulation calculates energy deposited by electrons and photons, while the
      analytical one only calculates energy deposited by source photons and
      photoelectrons; the Monte Carlo simulation accounts for electron-hole
      recombination, while the analytical one does not; and the Monte Carlo simulation
      randomly samples photon or electron path and accounts for particle interactions,
      while the analytical simulation assumes a linear trajectory. This study
      demonstrates that the Monte Carlo simulation will be a better choice to evaluate
      dose enhancement with nanoparticles in radiation therapy.

PMID- 27695328
TI  - The synergistic effect of TiO2 nanoporous modification and platelet-rich plasma
      treatment on titanium-implant stability in ovariectomized rats.
AB  - For several decades, titanium and its alloys have been commonly utilized for
      endosseous implantable materials, because of their good mechanical properties,
      chemical resistance, and biocompatibility. But associated low bone mass, wear and
      loss characteristics, and high coefficients of friction have limited their long
      term stable performance, especially in certain abnormal bone-metabolism
      conditions, such as postmenopausal osteoporosis. In this study, we investigated
      the effects of platelet-rich plasma (PRP) treatment and TiO2 nanoporous
      modification on the stability of titanium implants in osteoporotic bone. After
      surface morphology, topographical structure, and chemical changes of implant
      surface had been detected by scanning electron microscopy (SEM), atomic force
      microscopy, contact-angle measurement, and X-ray diffraction, we firstly assessed
      in vivo the effect of PRP treatment on osseointegration of TiO2-modified implants
      in ovariectomized rats by microcomputed tomography examinations, histology,
      biomechanical testing, and SEM observation. Meanwhile, the potential molecular
      mechanism involved in peri-implant osseous enhancement was also determined by
      quantitative real-time polymerase chain reaction. The results showed that this
      TiO2-modified surface was able to lead to improve bone implant contact, while PRP
      treatment was able to increase the implant surrounding bone mass. The synergistic
      effect of both was able to enhance the terminal force of implants drastically in
      biomechanical testing. Compared with surface modification, PRP treatment promoted
      earlier osteogenesis with increased expression of the RUNX2 and COL1 genes and
      suppressed osteoclastogenesis with increased expression of OPG and decreased
      levels of RANKL. These promising results show that PRP treatment combined with a
      TiO2-nanomodified surface can improve titanium-implant biomechanical stability in
      ovariectomized rats, suggesting a beneficial effect to support the success of
      implants in osteoporotic bone.

PMID- 27695331
TI  - Predicting episodic memory performance using different biomarkers: results from
      Argentina-Alzheimer's Disease Neuroimaging Initiative.
AB  - PURPOSE: Argentina-Alzheimer's Disease Neuroimaging Initiative (Arg-ADNI) is the
      first ADNI study to be performed in Latin America at a medical center with the
      appropriate infrastructure. Our objective was to describe baseline
      characteristics and to examine whether biomarkers related to Alzheimer's disease
      (AD) physiopathology were associated with worse memory performance. PATIENTS AND
      METHODS: Fifteen controls and 28 mild cognitive impairment and 13 AD dementia
      subjects were included. For Arg-ADNI, all biomarker parameters and
      neuropsychological tests of ADNI-II were adopted. Results of positron emission
      tomography (PET) with fluorodeoxyglucose and 11C-Pittsburgh compound-B (PIB-PET)
      were available from all participants. Cerebrospinal fluid biomarker results were
      available from 39 subjects. RESULTS: A total of 56 participants were included and
      underwent baseline evaluation. The three groups were similar with respect to
      years of education and sex, and they differed in age (F=5.10, P=0.01). Mean
      scores for the baseline measurements of the neuropsychological evaluation
      differed significantly among the three groups at P<0.001, showing a continuum in
      their neuropsychological performance. No significant correlations were found
      between the principal measures (long-delay recall, C-Pittsburgh compound-B scan,
      left hippocampal volume, and APOEepsilon4) and either age, sex, or education
      (P>0.1). Baseline amyloid deposition and left hippocampal volume separated the
      three diagnostic groups and correlated with the memory performance (P<0.001).
      CONCLUSION: Cross-sectional analysis of baseline data revealed links between
      cognition, structural changes, and biomarkers. Follow-up of a larger and more
      representative cohort, particularly analyzing cerebrospinal fluid and brain
      biomarkers, will allow better characterization of AD in our country.

PMID- 27695332
TI  - The positive effects of high-frequency right dorsolateral prefrontal cortex
      repetitive transcranial magnetic stimulation on memory, correlated with increases
      in brain metabolites detected by proton magnetic resonance spectroscopy in
      recently detoxified alcohol-dependent patients.
AB  - OBJECTIVE: To explore the effect of right dorsolateral prefrontal cortex (DLPFC)
      repetitive transcranial magnetic stimulation (rTMS) on memory, and its
      correlation with levels of hippocampal brain metabolites detected by proton
      magnetic resonance spectroscopy (1H-MRS) in recently detoxified alcohol-dependent
      patients. MATERIALS AND METHODS: In this randomized, double-blind sham-controlled
      trial, alcohol-dependent patients were enrolled and randomized into two groups:
      the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions) and the control
      group (sham stimulation). Memory function was assessed using Hopkins Verbal
      Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT
      R) before and after treatment. 1H-MRS was used to detect the levels of N-acetyl
      aspartic acid (NAA), choline (Cho), and creatine (Cr) in bilateral hippocampi
      before and after treatment. RESULTS: Thirty-eight patients (18 in the
      experimental group and 20 in the control group) were included in the analyses.
      The experimental group showed significantly greater changes in HVLT-R, BVMT-R,
      NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The
      percentage change in BVMT-R and HVLT-R correlated with the percentage change in
      NAA/Cr and Cho/Cr in the right brain. CONCLUSION: High-frequency right DLPFC rTMS
      was associated with improvement in memory dysfunction, which is correlated with
      levels of hippocampal brain metabolites detected by 1H-MRS in recently detoxified
      alcohol-dependent patients.

PMID- 27695333
TI  - The role of NMDAR antibody in the etiopathogenesis of schizophrenia.
AB  - Many authors have reported the presence of serum NMDAR antibodies in varying
      proportions of patients with schizophrenia; however, many others have not been
      able to confirm this. Because of the contradictory findings reported in various
      studies, more definitive research on this issue is required. Hence, we have
      investigated the NR1 subunit of NMDAR antibodies in patients with schizophrenia
      (n=49) and healthy controls (n=48). None of the investigated patients with
      schizophrenia and none of the healthy controls showed positive antibody against
      the NR1 subunit of the NMDAR. On the basis of this result, we conclude that the
      NR1 subunit of the NMDAR antibodies does not seem to have a role in
      schizophrenia.

PMID- 27695334
TI  - Effects of paroxetine-mediated inhibition of GRK2 expression on depression and
      cardiovascular function in patients with myocardial infarction.
AB  - BACKGROUND: Paroxetine is a selective serotonin reuptake inhibitor utilized in
      the treatment of depression and anxiety disorders. Recent studies have identified
      paroxetine as a G protein-coupled receptor kinase-2 (GRK2) inhibitor capable of
      reversing cardiac dysfunction and remodeling in experimental models of acute
      myocardial infarction (AMI). We determine the clinical importance of paroxetine
      on cardiac functions in patients having AMI with depression (AMID) in comparison
      with fluoxetine, an unrelated selective serotonin reuptake inhibitor that does
      not inhibit GRK2. METHODS: Diagnosis of depression was based on the 17-item
      Hamilton Depression Scale and Self-rating Depression Scale in AMI patients after
      hospital admission. AMID patients were randomly assigned to paroxetine or
      fluoxetine for treatment of depression. Heart rate variability and cardiac
      function were evaluated. GRK2 protein levels were measured using peripheral
      lymphocytes and Western blot. RESULTS: GRK2 expression in AMID patients was
      significantly higher than that in AMI patients without depression. In AMID
      patients, GRK2 levels were positively correlated with the 17-item Hamilton
      Depression Scale and the Self-rating Depression Scale scores, and negatively
      correlated with heart rate variability. Treatment of AMID patients with
      paroxetine significantly reduced the expression of GRK2, normalized the autonomic
      nervous system function, and improved cardiac performance. In contrast,
      fluoxetine normalized the autonomic nervous system but did not reduce the
      expression of GRK2 nor improved cardiac performance. CONCLUSION: This study
      suggests that paroxetine is effective for improving cardiac function in patients
      with AMID and such effect correlates with GRK2 reduction.

PMID- 27695330
TI  - Demineralization-remineralization dynamics in teeth and bone.
AB  - Biomineralization is a dynamic, complex, lifelong process by which living
      organisms control precipitations of inorganic nanocrystals within organic
      matrices to form unique hybrid biological tissues, for example, enamel, dentin,
      cementum, and bone. Understanding the process of mineral deposition is important
      for the development of treatments for mineralization-related diseases and also
      for the innovation and development of scaffolds. This review provides a thorough
      overview of the up-to-date information on the theories describing the possible
      mechanisms and the factors implicated as agonists and antagonists of
      mineralization. Then, the role of calcium and phosphate ions in the maintenance
      of teeth and bone health is described. Throughout the life, teeth and bone are at
      risk of demineralization, with particular emphasis on teeth, due to their
      anatomical arrangement and location. Teeth are exposed to food, drink, and the
      microbiota of the mouth; therefore, they have developed a high resistance to
      localized demineralization that is unmatched by bone. The mechanisms by which
      demineralization-remineralization process occurs in both teeth and bone and the
      new therapies/technologies that reverse demineralization or boost
      remineralization are also scrupulously discussed. Technologies discussed include
      composites with nano- and micron-sized inorganic minerals that can mimic
      mechanical properties of the tooth and bone in addition to promoting more natural
      repair of surrounding tissues. Turning these new technologies to products and
      practices would improve health care worldwide.

PMID- 27695335
TI  - Expanded DMPK repeats in dizygotic twins referred for diagnosis of autism versus
      absence of expanded DMPK repeats at screening of 330 children with autism.
AB  - Myotonic dystrophy type 1 (DM1) belongs to the broad spectrum of genetic
      disorders associated with autism spectrum disorders (ASD). ASD were reported
      predominantly in congenital and early childhood forms of DM1. We describe
      dizygotic twin boys with ASD who were referred for routine laboratory genetic
      testing and in whom karyotyping, FMR1 gene testing, and single nucleotide
      polymorphism array analysis yielded negative results. The father of the boys was
      later diagnosed with suspected DM1, and testing revealed characteristic DMPK gene
      expansions in his genome as well as in the genomes of both twins and their elder
      brother, who also suffered from ASD. In accord with previous reports on childhood
      forms of DM1, our patients showed prominent neuropsychiatric phenotypes
      characterized especially by hypotonia, developmental and language delay,
      emotional and affective lability, lowered adaptability, and social withdrawal.
      The experience with this family and multiple literature reports of ASD in DM1 on
      the one side but the lack of literature data on the frequency of DMPK gene
      expansions in ASD patients on the other side prompted us to screen the DMPK gene
      in a sample of 330 patients with ASD who were first seen by a geneticist before
      they were 10 years of age, before the muscular weakness, which may signal DM1,
      usually becomes obvious. The absence of any DMPK gene expansions in this cohort
      indicates that targeted DMPK gene testing can be recommended only in ASD patients
      with specific symptoms or family history suggestive of DM1.

PMID- 27695336
TI  - Varenicline improves motor and cognitive symptoms in early Huntington's disease.
AB  - The aim of this study was to describe the effects of varenicline, a smoking
      cessation aid that acts as a nicotinic agonist, on cognitive function in patients
      with early clinical Huntington's disease (HD) who were current smokers. Three
      gene-positive patients transitioning to symptomatic HD were evaluated using the
      Unified Huntington's Disease Rating Scale part I and III (motor and behavioral
      subscales) at baseline and after 4 weeks of treatment. Cognitive function was
      assessed using a touch screen computer-based neurocognitive test battery
      (IntegNeuro(r)). Varenicline (1 mg twice daily) significantly improved
      performance in executive function and emotional recognition tasks. Our case
      reports describe no clinically significant adverse effects and suggest that
      varenicline improves aspects of cognitive function in patients with early HD. A
      randomized controlled study is now underway.

PMID- 27695337
TI  - Clinical prediction rules for failed nonoperative reduction of intussusception.
AB  - PURPOSE: The nonoperative reduction of intussusception in children can be
      performed safely if there are no contraindications. Many risk factors associated
      with failed reduction were defined. The aim of this study was to develop a
      scoring system for predicting the failure of nonoperative reduction using various
      determinants. PATIENTS AND METHODS: The data were collected from Chiang Mai
      University Hospital and Siriraj Hospital from January 2006 to December 2012.
      Inclusion criteria consisted of patients with intussusception aged 0-15 years
      with no contraindications for nonoperative reduction. The clinical prediction
      rules were developed using significant risk factors from the multivariable
      analysis. RESULTS: A total of 170 patients with intussusception were included in
      the study. In the final analysis model, 154 patients were used for identifying
      the significant risk factors of failure of reduction. Ten factors clustering by
      the age of 3 years were identified and used for developing the clinical
      prediction rules, and the factors were as follows: body weight <12 kg (relative
      risk [RR] =1.48, P=0.004), duration of symptoms >48 hours (RR =1.26, P<0.001),
      vomiting (RR =1.63, P<0.001), rectal bleeding (RR =1.50, P<0.001), abdominal
      distension (RR =1.60, P=0.003), temperature >37.8 degrees C (RR =1.51, P<0.001),
      palpable mass (RR =1.26, P<0.001), location of mass (left over right side RR
      =1.48, P<0.001), ultrasound showed poor prognostic signs (RR =1.35, P<0.001), and
      the method of reduction (hydrostatic over pneumatic, RR =1.34, P=0.023).
      Prediction scores ranged from 0 to 16. A high-risk group (scores 12-16) predicted
      a greater chance of reduction failure (likelihood ratio of positive [LR+] =18.22,
      P<0.001). A low-risk group (score 0-11) predicted a lower chance of reduction
      failure (LR+ =0.79, P<0.001). The performance of the scoring model was 80.68%
      (area under the receiver operating characteristic curve). CONCLUSION: This
      scoring guideline was used to predict the results of nonoperative reduction and
      forecast the prognosis of the failed reduction. The usefulness of these
      prediction scores is for informing the parents before the reduction. This scoring
      system can be used as a guide to promote the possible referral of the cases to
      tertiary centers with facilities for nonoperative reduction if possible.

PMID- 27695338
TI  - Association of low serum aluminum level with mortality in hemodialysis patients.
AB  - BACKGROUND: The National Kidney Foundation-Kidney Disease Outcomes Quality
      Initiative recommends that the serum aluminum level (SAL) should be below 20 ug/L
      for patients with maintenance hemodialysis (MHD). However, serum aluminum may
      have toxic effects on MHD patients even when it is in the apparently acceptable
      range (below 20 ug/L). METHODS: The Medical Ethics Committee approved this study.
      Initially, 954 MHD patients in dialysis centers were recruited. A total of 901
      patients met the inclusion criteria and were followed-up for 1 year. Patients
      were stratified by SAL into four equal-sized groups: first quartile (<6 ug/L),
      second quartile (6-9 ug/L), third quartile (9-13 ug/L), and fourth quartile (>13
      ug/L). Demographic, biochemical, and dialysis-related data were obtained for
      analyses. A linear regression model was applied to identify factors associated
      with SAL. Cox proportional hazard model was used to determine the significance of
      variables in prediction of mortality. RESULTS: Only 9.3% of MHD patients had SALs
      of 20 ug/L or more. At the end of the follow-up, 54 patients (6%) died, and the
      main cause of death was cardiovascular disease. Kaplan-Meier survival analysis
      showed that patients in the fourth SAL quartile had higher mortality than those
      in the first SAL quartile (log rank test, chi2=13.47, P=0.004). Using the first
      quartile as reference, Cox multivariate analysis indicated that patients in the
      third quartile (hazard ratio =1.31, 95% confidence interval =1.12-1.53, P=0.038)
      and the fourth quartile (hazard ratio =3.19, 95% confidence interval =1.08-8.62,
      P=0.048) had increased risk of all-cause mortality. CONCLUSION: This study
      demonstrates that SAL, even when in an apparently acceptable range (below 20
      ug/L), is associated with increased mortality in MHD patients. The findings
      suggest that avoiding exposure of aluminum as much as possible is warranted for
      MHD patients.

PMID- 27695339
TI  - A Comparison of Morphine Delivery in Neonatal Opioid Withdrawal.
AB  - Current estimates of the prevalence of opioid withdrawal in newborns from the
      2012 Better Outcomes Registry and Network Ontario reveal that more than 4 births
      per 1000 display recognizable symptoms of neonatal abstinence syndrome (NAS).
      With a growing consensus surrounding aspects of newborn opioid withdrawal care,
      clinicians might agree that all infants exposed to maternal opioids require
      supportive observation and care to ensure appropriate adaptation and growth in
      the newborn period and, likewise, that there exists a smaller percentage of
      newborns who require additional pharmacotherapy. However, due to the dearth of
      comparative studies of NAS tools, there remains a lack of evidence to support the
      use of a specific NAS method of scoring or treatment. Two types of NAS treatment
      protocols currently in use include a symptom-only versus weight-based protocols.
      Our Neonatal Intensive Care Unit (NICU) has used both models. A formal structured
      NAS tool and weight-based morphine delivery system began in our NICU in 1999. We
      audited all newborns with known exposure to maternal opioids in our NICU from the
      years 2000 to 2014. The Finnegan scoring tool was used throughout all years of
      the chart audit. Modifications made to the Finnegan scoring tool from the MOTHER
      study were adapted for use in our NICU at the same time as adopting the Johns
      Hopkins model of symptom-only based morphine delivery in 2006. The objective of
      this comparative study using a retrospective chart audit is to compare length of
      stay (LOS) and total accumulative morphine dose across these two morphine
      delivery protocols. Our audit revealed that there were a significantly higher
      proportion of newborns in the symptom-only model that received morphine and,
      perhaps accordingly, also had a significantly higher LOS compared to those in the
      weight-based model. Comparing only those infants who did receive morphine, the
      comparative total accumulative dose of morphine and LOS were not significantly
      different between the weight-based and symptom-only morphine delivery models.

PMID- 27695340
TI  - Improving perioperative care for adolescent idiopathic scoliosis patients: the
      impact of a multidisciplinary care approach.
AB  - The complex nature of the surgical treatment of adolescent idiopathic scoliosis
      (AIS) requires a wide variety of health care providers. A well-coordinated,
      multidisciplinary team approach to the care of these patients is essential for
      providing high-quality care. This review offers an up-to-date overview of the
      numerous interventions and safety measures for improving outcomes after AIS
      surgery throughout the perioperative phases of care. Reducing the risk of
      potentially devastating and costly complications after AIS surgery is the
      responsibility of every single member of the health care team. Specifically, this
      review will focus on the perioperative measures for preventing surgical site
      infections, reducing the risk of neurologic injury, minimizing surgical blood
      loss, and preventing postoperative complications. Also, the review will highlight
      the postoperative protocols that emphasize early mobilization and accelerated
      discharge.

PMID- 27695341
TI  - Novel Approach to Analyzing MFE of Noncoding RNA Sequences.
AB  - Genomic studies have become noncoding RNA (ncRNA) centric after the study of
      different genomes provided enormous information on ncRNA over the past decades.
      The function of ncRNA is decided by its secondary structure, and across
      organisms, the secondary structure is more conserved than the sequence itself. In
      this study, the optimal secondary structure or the minimum free energy (MFE)
      structure of ncRNA was found based on the thermodynamic nearest neighbor model.
      MFE of over 2600 ncRNA sequences was analyzed in view of its signal properties.
      Mathematical models linking MFE to the signal properties were found for each of
      the four classes of ncRNA analyzed. MFE values computed with the proposed models
      were in concordance with those obtained with the standard web servers. A total of
      95% of the sequences analyzed had deviation of MFE values within +/-15% relative
      to those obtained from standard web servers.

PMID- 27695342
TI  - Limb-salvage treatment of en-block resected distal femoral tumors with
      endoprosthesis of all-polyethylene tibial component: a 9-year follow-up study.
AB  - OBJECTIVE: To evaluate the medium-term outcome of limb-salvage surgery using all
      polyethylene tibial endoprosthetic replacement following en-block resection for
      distal femoral tumors. METHODS: Forty-nine patients with distal femoral tumor
      were treated between June 2006 and June 2012. The follow-up period was 6-110
      months (average 53.4 months). The prosthetic survival was analyzed using the
      Kaplan-Meier method. The classification of failure of limb salvage after
      reconstructive surgery for bone tumors was adapted. Limb function was evaluated
      with the scoring system of the Musculoskeletal Tumor Society (MSTS). RESULTS:
      Complications were observed in six cases (12.2%). Four suffered infection around
      the prosthesis, of which two cases were treated with debridement, drainage, and
      antibiotics without removal of the prosthesis, and the other two cases underwent
      amputation. Two cases were identified as radiographically loose at 7 year follow
      up and did not require revision surgery. One patient underwent amputation due to
      local recurrence. Failure of limb salvage occurred in nine cases (18.4%), of
      which two cases were of type 1A, two cases of type 2B, three cases of type 4A,
      one case of type 4B, and one case of type 5A. The mean MSTS score was 84.3%.
      Twelve cases died due to distant metastases (24.5%), and the average survival
      time for these patients was 13.5 months. Thirty-seven patients survived (75.5%),
      for whom the average follow-up time was 66.3 months and the 5-year prosthetic
      survival rate was 88.2%. CONCLUSION: The outcome of medium-term and long-term
      clinical follow-up was satisfactory. All-polyethylene tibial endoprosthetic
      replacement following en-block resection can be an alternative method of limb
      salvage for distal femoral tumors.

PMID- 27695343
TI  - A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy
      versus radical hysterectomy alone in patients with stage II cervical squamous
      cell carcinoma presenting as a bulky mass.
AB  - OBJECTIVE: In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC)
      for stage II cervical squamous cell carcinoma with a bulky mass, we
      retrospectively compared patients receiving NAC followed by radical hysterectomy
      (RH; NAC group) with patients who underwent RH without NAC (Ope group). PATIENTS
      AND METHODS: The study period was from June 2002 to March 2014. The subjects were
      28 patients with a stage II bulky mass in the NAC group and 17 such patients in
      the Ope group. The chi-square test was used to compare operative time, volume of
      intraoperative blood loss, use of blood transfusion, and time from surgery to
      discharge between the two groups. Moreover, the log-rank test using the Kaplan
      Meier method was performed to compare disease-free survival (DFS) and overall
      survival (OS) between the groups. RESULTS: There were no statistically
      significant differences between the two groups in operative time, volume of
      intraoperative blood loss, or use of blood transfusion. However, the time from
      surgery to discharge was 18 days (14-25 days) in the NAC group and 25 days (21-34
      days) in the Ope group; the patients in the NAC group were discharged earlier
      (P=0.032). The hazard ratio for DFS in the NAC group as compared with that in the
      Ope group was 0.36 (95% CI 0.08-0.91), and the 3-year DFS rates were 81.2% and
      41.0%, respectively (P=0.028). Moreover, the hazard ratio for OS was 0.39 (95% CI
      0.11-1.24), and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101).
      CONCLUSION: NAC with cisplatin and irinotecan was confirmed to prolong DFS as
      compared with RH alone. The results of this study suggest that NAC might be a
      useful adjunct to surgery in the treatment of stage II squamous cell carcinoma
      presenting as a bulky mass.

PMID- 27695344
TI  - Primary gastric anaplastic lymphoma kinase-negative anaplastic large-cell
      lymphoma.
AB  - INTRODUCTION: Most primary stomach lymphomas are now recognized to originate from
      B-cell. Primary gastric anaplastic lymphoma kinase (ALK)-negative anaplastic
      large-cell lymphoma (ALCL) as shown in this case is very rare. CASE REPORT: A 59
      year-old man presented with a 1-month history of epigastric pain. Computed
      tomography showed a tumor in the stomach with perigastric lymphadenopathy. Biopsy
      of the tumor with gastroendoscopy showed ALCL. Bone marrow aspiration and
      trephine biopsy showed no infiltration. A diagnosis of primary gastric ALK
      negative ALCL was made. The patient was first treated with four cycles of
      cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, but his
      condition did not show improvement. Then he was treated with two cycles of
      hyperfractionated cyclophosphamide, vincristine, doxorubicin, and
      dexamethasone/methotrexate and cytarabine (Hyper-CVAD/MA) regimen. In spite of
      these treatments, he still died of disease progression. CONCLUSION: The prognosis
      of ALK-negative ALCLs is usually worse than ALK-positive ALCLs. In this case, the
      patient was not responsive to a multidrug chemotherapy with CHOP and Hyper
      CVAD/MA.

PMID- 27695345
TI  - Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell
      carcinoma.
AB  - Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left
      untreated, BCCs can become locally aggressive or even metastasize. Currently
      available treatments include local destruction, surgery, and radiation. Systemic
      options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly
      activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are
      targeted agents that inhibit the aberrant activation of the Hh pathway, with
      smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor
      that was recently approved by the US Food and Drug Administration. This review
      focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the
      treatment of advanced BCC.

PMID- 27695346
TI  - MicroRNA expression profiles predict progression and clinical outcome in lung
      adenocarcinoma.
AB  - Lung cancer is one of the leading causes of cancer death worldwide. Accumulating
      evidence has indicated that microRNAs (miRNAs) can be proposed as promising
      diagnostic and prognostic markers for various cancers. The current study analyzed
      the miRNA expression profiles of 418 lung adenocarcinoma (LUAD) cases obtained
      from The Cancer Genome Atlas dataset, with the aim to investigate the
      relationship of miRNAs with progression and prognosis of LUAD. A total of 185
      miRNAs were found to be differentially expressed between LUAD tumor tissues and
      adjacent normal tissues. Among them, 13, 10, 0, and 10 miRNAs were discovered to
      be associated with pathologic T, N, M, and Stage, respectively. Interestingly,
      mir-200 family (mir-200a, mir-200b, and mir-429) was shown to play a critical
      role in the progression of LUAD. In the multivariate Cox regression analysis, mir
      1468 (P=0.009), mir-212 (P=0.026), mir-3653 (P=0.012), and mir-31 (P=0.002) were
      significantly correlated with recurrence-free survival. With regard to overall
      survival, mir-551b (P=0.011), mir-3653 (P=0.016), and mir-31 (P=0.001) were
      proven as independent prognostic markers. In summary, this study identified the
      cancer-specific miRNAs that may predict the progression and prognosis of LUAD.

PMID- 27695347
TI  - Clinical comparative investigation of efficacy and toxicity of cisplatin plus
      gemcitabine or plus Abraxane as first-line chemotherapy for stage III/IV non
      small-cell lung cancer.
AB  - PURPOSE: The purpose of this study was to observe the clinical efficacy and
      toxicity of cisplatin in combination with gemcitabine or Abraxane as first-line
      chemotherapy for stage III/IV non-small-cell lung cancer (NSCLC). PATIENTS AND
      METHODS: A total of 200 patients with advanced NSCLC, which was confirmed by
      pathology or cytology, were enrolled into our research by reviewing previous
      complete and retrievable medical records data of our hospital. A total of 100
      patients were treated with gemcitabine (1,000 mg/m2, day 1 and day 8) in
      combination with cisplatin (75 mg/m2, days 1-3; GP group) and another 100
      patients were treated with Abraxane (260 mg/m2, day 1) in combination with
      cisplatin (75 mg/m2, days 1-3; TP group). Twenty-one days were required to
      complete one cycle; at least two cycles were completed by each group. RESULTS:
      For the 100 patients in the GP group, the effective response rate (RR) was 27%,
      the disease control rate (DCR) was 63%, and the median progression-free survival
      (PFS) time was 8 months. For the 100 patients in the TP group, the RR was 52%,
      the DCR was 75%, and the median PFS was 20 months. There was significant
      difference in RR (P<0.001), but no significant difference in DSR and PFS
      (P>0.05). Common treatment-related adverse events were hematologic toxicity and
      gastrointestinal reaction. Hematologic toxicity mainly included decreased white
      blood cells and platelets. The differences between the two groups were
      statistically significant (P<0.05). Gastrointestinal reaction mainly included
      nausea and vomiting. There was no statistical significance between them
      (P=0.805). For the 85 patients with squamous carcinoma in the TP group, the RR
      was 60%, the DCR was 78%, and the median PFS was 7.5 months. For the 85 patients
      with squamous carcinoma in the GP group, the RR was 36%, the DCR was 62%, and the
      median PFS was 18.5 months. There was significant difference in RR (P=0.024), but
      no significant difference in DSR and PFS (P>0.05). For the 115 patients with
      adenocarcinoma in the TP group, the RR was 47%, the DCR was 73%, and the median
      PFS was 8 months. For the 115 patients with adenocarcinoma in the GP group, the
      RR was 20%, the DCR was 64%, and the median PFS was 20.5 months. There was
      significant difference in RR (P=0.003), but no significant difference in DCR and
      PFS (P>0.05). CONCLUSION: The efficacy of cisplatin in combination with Abraxane
      is better than that with gemcitabine in the treatment of NSCLC, and the treatment
      has less risk of hematologic toxicity.

PMID- 27695348
TI  - A negative regulation loop of long noncoding RNA HOTAIR and p53 in non-small-cell
      lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer-related
      death worldwide, and the 5-year survival rate is still low despite advances in
      diagnosis and therapeutics. A long noncoding RNA (lncRNA) HOX antisense
      intergenic RNA (HOTAIR) has been revealed to play important roles in NSCLC
      carcinogenesis but the detailed mechanisms are still unclear. In the current
      study, we aimed to investigate the regulation between the lncRNA HOTAIR and p53
      in the NSCLC patient samples and cell lines. Our results showed that HOTAIR
      expression was significantly higher in the cancer tissues than that in the
      adjacent normal tissue, and was negatively correlated with p53 functionality
      rather than expression. When p53 was overexpressed in A549 cells, the lncRNA
      HOTAIR expression was downregulated, and the cell proliferation rate and cell
      invasion capacity decreased as a consequence. We identified two binding sites of
      p53 on the promoter region of HOTAIR, where the p53 protein would bind to and
      suppress the HOTAIR mRNA transcription. Inversely, overexpression of lncRNA
      HOTAIR inhibited the expression of p53 in A549 cells. Mechanistic studies
      revealed that HOTAIR modified the promoter of p53 and enhanced histone H3 lysine
      27 trimethylation (H3K27me3). These studies identified a specific negative
      regulation loop of lncRNA HOTAIR and p53 in NSCLC cells, which revealed a new
      understanding of tumorigenesis in p53 dysfunction NSCLC cells.

PMID- 27695349
TI  - Proton beam therapy: clinical utility and current status in prostate cancer.
AB  - Proton beam therapy has recently become available to a broader population base.
      There remains much controversy about its routine use in prostate cancer. We
      provide an analysis of the existing literature regarding efficacy and toxicity of
      the technique. Currently, the use of proton beam therapy for prostate cancer is
      largely dependent on continued reimbursement for the practice. While there are
      potential benefits supporting the use of protons in prostate cancer, the low risk
      of toxicity using existing techniques and the high cost of protons contribute to
      lower the value of the technique.

PMID- 27695350
TI  - Study of the correlations between fractional exhaled nitric oxide in exhaled
      breath and atopic status, blood eosinophils, FCER2 mutation, and asthma control
      in Vietnamese children.
AB  - INTRODUCTION: Fractional exhaled nitric oxide (FENO) is a biomarker of airway
      inflammation in asthma. The measurement of FENO is utilized to assist in the
      diagnosis and treatment of children with asthma, especially for those treated
      with inhaled corticosteroids. OBJECTIVES: The aims of this study were to evaluate
      the correlations between FENO and atopic status, blood eosinophil levels, FCER2
      mutation, and asthma control in Vietnamese children. SUBJECTS AND METHODS: This
      was a prospective and descriptive study approved by the local Ethical Board. All
      children with uncontrolled asthma, seen in the National Hospital of Pediatrics
      (Hanoi, Vietnam), were included. Exhaled breath FENO, blood eosinophils, skin
      prick test, total IgE, asthma control test (ACT), and FCER2 gene polymorphism
      were performed at inclusion. They were followed up at 3 months to evaluate
      clinical status, FENO levels, and ACT. RESULTS: Forty-two children with
      uncontrolled asthma with a mean age of 10+/-3 years (6-16 years) were included.
      The male/female ratio was 2.5/1. The mean FENO levels were 26+/-25 ppb. FENO was
      significantly higher in patients with a positive skin prick test for respiratory
      allergens (P<0.05). FENO was significantly correlated with blood eosinophil
      levels (r=0.5217; P=0.0004). Five of the 32 subjects (15.6%) had a mutation of
      FCER2 gene (rs28364072 SNP). In this group, the levels of FENO were highest (37+/
      10 ppb; P<0.05). The levels of FENO were significantly decreased after 3 months
      of treatment (17+/-8 ppb vs 26+/-25 ppb; P<0.05). Significant correlations
      between inhaled corticosteroid doses and FENO levels occurred at 1 and 3 months
      (r=0.415, P=0.007; r=0.396, P=0.010; respectively). There were no correlations
      between FENO levels, ACT, and daily use of salbutamol. After 3 months, asthma
      remained uncontrolled in 22.2% of children. CONCLUSION: The measurement of FENO
      levels is a useful and feasible tool to predict clinical, biological, and asthma
      control in Vietnamese children.

PMID- 27695352
TI  - Cost analysis of magnetically controlled growing rods compared with traditional
      growing rods for early-onset scoliosis in the US: an integrated health care
      delivery system perspective.
AB  - PURPOSE: Traditional growing rod (TGR) for early-onset scoliosis (EOS) is
      effective but requires repeated invasive surgical lengthenings under general
      anesthesia. Magnetically controlled growing rod (MCGR) is lengthened
      noninvasively using a hand-held magnetic external remote controller in a
      physician office; however, the MCGR implant is expensive, and the cumulative cost
      savings have not been well studied. We compared direct medical costs of MCGR and
      TGR for EOS from the US integrated health care delivery system perspective. We
      hypothesized that over time, the MCGR implant cost will be offset by eliminating
      repeated TGR surgical lengthenings. METHODS: For both TGR and MCGR, the economic
      model estimated the cumulative costs for initial implantation, lengthenings,
      revisions due to device failure, surgical-site infections, device exchanges (at
      3.8 years), and final fusion, over a 6-year episode of care. Model parameters
      were estimated from published literature, a multicenter EOS database of US
      institutions, and interviews. Costs were discounted at 3.0% annually and
      represent 2015 US dollars. RESULTS: Of 1,000 simulated patients over 6 years,
      MCGR was associated with an estimated 270 fewer deep surgical-site infections and
      197 fewer revisions due to device failure compared with TGR. MCGR was projected
      to cost an additional $61 per patient over the 6-year episode of care compared
      with TGR. Sensitivity analyses indicated that the results were sensitive to
      changes in the percentage of MCGR dual rod use, months between TGR lengthenings,
      percentage of hospital inpatient (vs outpatient) TGR lengthenings, and MCGR
      implant cost. CONCLUSION: Cost neutrality of MCGR to TGR was achieved over the 6
      year episode of care by eliminating repeated TGR surgical lengthenings. To our
      knowledge, this is the first cost analysis comparing MCGR to TGR - from the US
      provider perspective - which demonstrates the efficient provision of care with
      MCGR.

PMID- 27695351
TI  - Lemierre's syndrome: current perspectives on diagnosis and management.
AB  - This is a systematic review of cases with Lemierre's syndrome (LS) in the past 5
      years. LS is characterized by sepsis often evolving after a sore throat or
      tonsillitis and then complicated by various septic emboli and thrombosis of the
      internal jugular vein. Symptoms include sepsis, pain, and/or swelling in the
      throat or neck, as well as respiratory symptoms. Laboratory findings show
      elevated infectious parameters and radiological findings show thrombosis of the
      internal jugular vein and emboli in the lungs or other organs. The syndrome is
      often associated with an infection with Fusobacterium necrophorum. We found a
      total of 137 cases of LS, of which 47 were infected with F. necrophorum and
      others with Staphylococcus and Streptococcus. Complications of this rare but
      severe disease included osteomyelitis, meningitis, and acute respiratory distress
      syndrome. Mortality was extremely high in the pre-antibiotic era but has
      diminished with the advent of antibiotics. This review showed a mortality rate of
      only 2% of which none of the cases involved fusobacteria. Duration of treatment
      varied; a 4-6-week course of carbapenem or piperacillin/tazobactam in combination
      with metronidazole was optimum. Other treatment options included anticoagulants
      in 46% of cases, which is unwarrantedly high, as to date, no evidence of the
      positive effects of anticoagulants in LS exists. Only two cases had ligation of
      the internal jugular vein performed. This review confirms the rare, but severe
      aspects of LS. Mortality from LS in this day and age appears to be low, however
      the syndrome is difficult to recognize, and still requires the full attention of
      the clinician.

PMID- 27695353
TI  - Consequences of inaccurate hepatitis C virus genotyping on the costs of
      prescription of direct antiviral agents in an Italian district.
AB  - Available commercial assays may yield inaccurate hepatitis C virus (HCV) genotype
      assignment in up to 10% of cases. We investigated the cost-effectiveness of re
      evaluating HCV genotype by population sequencing, prior to choosing a direct
      acting antiviral (DAA) regimen. Between March and September 2015, HCV sequence
      analysis was performed in order to confirm commercial LiPA-HCV genotype
      (Versant(r) HCV Genotype 2.0) in patients eligible for treatment with DAAs. Out
      of 134 consecutive patients enrolled, sequencing yielded 21 (15.7%) cases of
      discordant results. For three cases of wrong genotype assignment, the putative
      reduction in efficacy was gauged between 15% and 40%. Among the eight cases for
      whom G1b was assigned by commercial assays instead of G1a, potentially suboptimal
      treatments would have been prescribed. Finally, for five patients with G1 and
      indeterminate subtype, the choice of regimens would have targeted the worst
      option, with a remarkable increase in costs, as in the case of the four mixed HCV
      infections for whom pan-genotypic regimens would have been mandatory. Precise
      assignment of HCV genotype and subtype by sequencing may, therefore, be more
      beneficial than expected, until more potent pan-genotypic regimens are available
      for all patients.

PMID- 27695354
TI  - Management of familial benign chronic pemphigus.
AB  - Benign familial chronic pemphigus or Hailey-Hailey disease is caused by an
      autosomal dominant mutation in the ATP2C1 gene leading to suprabasilar
      acantholysis. The disease most commonly affects intertriginous areas
      symmetrically. The chronic nature of the disease and multiple recurrences make
      the disease bothersome for patients and a treatment challenge for physicians.
      Treatments include topical and/or systemic agents and surgery including laser.
      This review summarizes the available treatment options.

PMID- 27695355
TI  - Influence of Saccharomyces boulardii CNCM I-745on the gut-associated immune
      system.
AB  - BACKGROUND: The probiotic Saccharomyces boulardii CNCM I-745 (also known as
      Saccharomyces cerevisiae HANSEN CBS 5926; in the following S. boulardii) has
      proven its effectiveness in preventive and therapeutic treatment of many
      gastrointestinal diseases, especially diseases associated with acute diarrhea. In
      particular, antibiotic-associated diarrhea, Clostridium difficile-associated
      diarrhea, traveller's diarrhea, as well as acute diarrhea due to common viral and
      bacterial infections in children and adults. AIM: The aim of this review is to
      summarize the experimental studies elucidating the molecular and immunological
      mechanisms by which these clinically proven effects are archived, with an
      emphasis on the gut-associated immune system. The main focus is laid on anti
      inflammatory and immune-modulatory action of S. boulardii involved in bacterial
      or enterotoxin-mediated diarrhea and inflammation. An attempt is made to
      differentiate between the effects associated with cellular versus soluble factors
      and between prophylactic and therapeutic effects. METHODS: A literature search
      was performed in PubMed/PubMed Central for the effects of S. boulardii on the gut
      associated immune system (focus acute diarrhea). RESULTS AND CONCLUSION: S.
      boulardii exhibits its positive effect by the direct effects on pathogens or
      their toxins as well as by influencing the host's infection-induced signaling
      cascades and its innate and adaptive immune system. The combination of these
      mechanisms results in a reduction of the pathogens' ability for adhesion or
      colonization and an attenuation of the overreacting inflammatory immune response.
      Thereby, the integrity of the intestinal epithelial cell layer is preserved or
      restored, and the diarrheic leakage of fluids into the intestinal lumen is
      attenuated.

PMID- 27695358
TI  - The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and
      safety profile in patients with alcohol addiction during the exacerbation of the
      addiction.
AB  - BACKGROUND: Today, it is proved that isoenzymes CYP2D6 and CYP3A4 are involved in
      metabolism of haloperidol. In our previous investigation, we found a medium
      correlation between the efficacy and safety of haloperidol and the activity of
      CYP3A4 in patients with alcohol abuse. OBJECTIVE: The aim of this study was to
      evaluate the correlation between the activity of CYP2D6 and the efficacy and
      safety of haloperidol in patients with diagnosed alcohol abuse. METHODS: The
      study involved 70 men (average age: 40.83+/-9.92 years) with alcohol addiction. A
      series of psychometric scales were used in the research. The activity of CYP2D6
      was evaluated by high-performance liquid chromatography with mass spectrometry
      using the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline to pinoline.
      Genotyping of CYP2D6 (1846G>A) was performed using real-time polymerase chain
      reaction. RESULTS: According to results of correlation analysis, statistically
      significant values of Spearman correlation coefficient (rs) between the activity
      of CYP2D6 and the difference of points in psychometric scale were obtained in
      patients receiving haloperidol in injection form (Sheehan Clinical Anxiety Rating
      Scale =-0.721 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect Rating
      Scale =0.692 [P<0.001]) and in those receiving haloperidol in tablet form (Covi
      Anxiety Scale =-0.851 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect
      Rating Scale =0.797 [P<0.001]). CONCLUSION: This study demonstrated the
      correlations between the activity of CYP2D6 isozyme and the efficacy and safety
      of haloperidol in patients with alcohol addiction.

PMID- 27695357
TI  - Update on current management of chronic kidney disease in patients with HIV
      infection.
AB  - The prevalence of HIV-associated chronic kidney disease (CKD) varies
      geographically and depends on the definition of CKD used, ranging from 4.7% to
      38% globally. The incidence, however, has decreased with the use of effective
      combined antiretroviral therapy (cART). A wide variety of histological patterns
      are seen in HIV-associated kidney diseases that include glomerular and
      tubulointerstitial pathology. In resource-rich settings, there has been a plateau
      in the incidence of end-stage renal disease secondary to HIV-associated
      nephropathy (HIVAN). However, the prevalence of end-stage renal disease in HIV
      positive individuals has risen, mainly due to increased longevity on cART. There
      is a disparity in the occurrence of HIVAN among HIV-positive individuals such
      that there is an 18- to 50-fold increased risk of developing kidney disease among
      HIV-positive individuals of African descent aged between 20 and 64 years and who
      have a poorer prognosis compared with their European descent counterparts,
      suggesting that genetic factors play a vital role. Other risk factors include
      male sex, low CD4 counts, and high viral load. Improvement in renal function has
      been observed after initiation of cART in patients with HIV-associated CKD.
      Treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor
      blocker is recommended, when clinically indicated in patients with confirmed or
      suspected HIVAN or clinically significant albuminuria. Other standard management
      approaches for patients with CKD are recommended. These include addressing other
      cardiovascular risk factors (appropriate use of statins and aspirin, weight loss,
      cessation of smoking), avoidance of nephrotoxins, and management of serum
      bicarbonate and uric acid, anemia, calcium, and phosphate abnormalities. Early
      diagnosis of kidney disease by screening of HIV-positive individuals for the
      presence of kidney disease is critical for the optimal management of these
      patients. Screening for the presence of kidney disease upon detection of HIV
      infection and annually thereafter in high-risk populations is recommended.

PMID- 27695356
TI  - Managing eosinophilic esophagitis: challenges and solutions.
AB  - Eosinophilic esophagitis (EoE) is a chronic and progressive immune-mediated
      condition defined by symptoms of esophageal dysfunction and dense eosinophilic
      infiltration of the esophageal mucosa. Therapies consist of anti-eosinophilic
      medications and specialized diets aimed to decrease the progression of EoE and
      alleviate its symptoms, namely, dysphagia and food impaction. Assessing response
      to therapy remains challenging, as treatment end points are not well defined and
      currently consist of clinical, histologic, and endoscopic features. Newer
      validated measures may help standardize treatment end points. Emerging data
      support the use of maintenance therapy, which may reduce disease progression.
      Optimal dosages, delivery techniques, and duration of treatment need to be
      determined. When features of fibrostenosis develop, esophageal dilation is a safe
      and effective adjunctive strategy for improving symptoms. In EoE cases refractory
      to conventional treatments, newer therapies targeting inflammatory mediators and
      cytokines are on the horizon.

PMID- 27695359
TI  - Parecoxib increases muscle pain threshold and relieves shoulder pain after
      gynecologic laparoscopy: a randomized controlled trial.
AB  - OBJECTIVES: Postlaparoscopic shoulder pain (PLSP) remains a common problem after
      laparoscopies. The aim of this study was to investigate the correlation between
      pressure pain threshold (PPT) of different muscles and PLSP after gynecologic
      laparoscopy, and to explore the effect of parecoxib, a cyclooxygenase-2
      inhibitor, on the changes of PPT. MATERIALS AND METHODS: The patients were
      randomly allocated into two groups; group P and group C. In group P, parecoxib 40
      mg was intravenously infused at 30 minutes before surgery and 8 and 20 hours
      after surgery. In group C, normal saline was infused at the corresponding time
      point. PPT assessment was performed 1 day before surgery and at postoperative 24
      hours by using a pressure algometer at bilateral shoulder muscles (levator
      scapulae and supraspinatus) and forearm (flexor carpi ulnaris). Meanwhile,
      bilateral shoulder pain was evaluated through visual analog scale score at 24
      hours after surgery. RESULTS: Preoperative PPT level of the shoulder, but not of
      the forearm, was significantly and negatively correlated with the intensity of
      ipsilateral PLSP. In group C, PPT levels of shoulder muscles, but not of forearm
      muscles, decreased after laparoscopy at postoperative 24 hours. The use of
      parecoxib significantly improved the decline of PPT levels of bilateral shoulder
      muscles (all P<0.01). Meanwhile, parecoxib reduced the incidence of PLSP (group
      P: 45% vs group C: 83.3%; odds ratio: 0.164; 95% confidence interval: 0.07-0.382;
      P<0.001) and the intensity of bilateral shoulder pain (both P<0.01). CONCLUSION:
      Preoperative PPT levels of shoulder muscles are closely associated with the
      severity of shoulder pain after gynecologic laparoscopy. PPT levels of shoulder
      muscles, but not of forearm muscles, significantly decreased after surgery.
      Parecoxib improved the decrease of PPT and relieved PLSP.

PMID- 27695360
TI  - Translation, adaptation, and validation of the behavioral pain scale and the
      critical-care pain observational tools in Taiwan.
AB  - This study describes the cultural adaptation and testing of the behavioral pain
      scale (BPS) and the critical-care pain observation tools (CPOT) for pain
      assessment in Taiwan. The cross-cultural adaptation followed the steps of
      translation, including forward translation, back-translation, evaluation of the
      translations by a committee of experts, adjustments, and then piloting of the
      prefinal versions of the BPS and the CPOT. A content validity index was used to
      assess content validities of the BPS and the CPOT, with 0.80 preset as the level
      that would be regarded as acceptable. The principal investigator then made
      adjustments when the content validity index was <0.80. The pilot test was
      performed with a sample of ten purposively selected patients by 2 medical staff
      from a medical care center in Taiwan. The BPS and the CPOT are adequate
      instruments for the assessment of pain levels in patients who cannot communicate
      due to sedation and ventilation treatments.

PMID- 27695362
TI  - Reduction of central neuropathic pain with ketamine infusion in a patient with
      Ehlers-Danlos syndrome: a case report.
AB  - OBJECTIVE: Ehlers-Danlos syndrome frequently causes acute and chronic pain
      because of joint subluxations and dislocations secondary to hypermobility.
      Current treatments for pain related to Ehlers-Danlos syndrome and central pain
      syndrome are inadequate. This case report discusses the therapeutic use of
      ketamine intravenous infusion as an alternative. CASE REPORT: A 27-year-old
      Caucasian female with a history of Ehlers-Danlos syndrome and spinal cord
      ischemic myelopathy resulting in central pain syndrome, presented with severe
      generalized body pain refractory to multiple pharmacological interventions. After
      a 7-day course of ketamine intravenous infusion under controlled generalized
      sedation in the intensive care unit, the patient reported a dramatic reduction in
      pain levels from 7-8 out of 10 to 0-3 out of 10 on a numeric rating scale and had
      a significant functional improvement. The patient tolerated a reduction in her
      pain medication regimen, which originally included opioids, gabapentin,
      pregabalin, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs.
      CONCLUSION: Ketamine infusion treatment has been used in various pain syndromes,
      including central neuropathic pain, ischemic pain, and regional pain syndrome.
      Reports have suggested that ketamine modulates pain by the regression of N-methyl
      D-aspartate receptor to a resting state. As such, propagation of nociceptive
      signal to brain is interrupted allowing for the restoration of physiological
      balance between pain inhibition and facilitation. The present report shows that
      this treatment option can be used in patients with refractory central pain
      syndrome in the setting of spinal cord myelopathy secondary to Ehlers-Danlos
      syndrome. In addition, as seen in this case, this protocol can potentially
      decrease the chronic use of pain medication, such as opioids.

PMID- 27695361
TI  - Detection of central circuits implicated in the formation of novel pain memories.
AB  - Being able to remember physically and emotionally painful events in one's own
      past may shape behavior, and can create an aversion to a variety of situations.
      Pain imagination is a related process that may include recall of past
      experiences, in addition to production of sensory and emotional percepts without
      external stimuli. This study aimed to understand 1) the central nervous system
      processes that underlie pain imagination, 2) the retrieval of pain memories, and
      3) to compare the latter with visual object memory. These goals were achieved by
      longitudinally investigating brain function with functional magnetic resonance
      imaging in a unique group of healthy volunteers who had never experienced tooth
      pain. In these subjects, we compared brain responses elicited during three
      experimental conditions in the following order: imagination of tooth pain (pain
      imagination), remembering one's own house (object memory), and remembrance of
      tooth pain following an episode of induced acute tooth pain (pain memory). Key
      observations stemming from group-level conjunction analyses revealed common
      activation in the posterior parietal cortex for both pain imagination and pain
      memory, while object and pain memory each had strong activation predominantly
      within the middle frontal gyrus. When contrasting pain imagination and memory,
      significant activation differences were observed in subcortical structures (ie,
      parahippocampus - pain imagination > pain memory; midbrain - pain memory > pain
      imagination). Importantly, these findings were observed in the presence of
      consistent and reproducible psychophysical and behavioral measures that informed
      on the subjects' ability to imagine novel and familiar thoughts, as well as the
      subjects' pain perception.

PMID- 27695364
TI  - Health service use among children with and without eczema, asthma, and hay fever.
AB  - BACKGROUND: Atopic diseases, for example, eczema, asthma, and hay fever, are
      among the most common chronic diseases of childhood. Knowledge on health service
      use among children with atopic disease is limited. This study aimed to
      investigate the total use and costs of health services for children with and
      without eczema, asthma, and hay fever in a Danish general population. METHODS: We
      conducted a health survey with four complete birth cohorts from the City of
      Copenhagen. Individual questionnaire data on eczema, asthma, and hay fever for
      children aged 3, 6, 11, and 15 years were linked to register information on use
      and costs of health services and prescribed medication and parental education. In
      total 9,720 children participated (50.5%). RESULTS: We found increased health
      service use (number of additional consultations per year [95% confidence
      interval]) among children with current eczema symptoms (1.77 [1.29-2.26]),
      current asthma symptoms (2.53 [2.08-2.98]), and current hay fever symptoms (1.21
      [0.74-1.67]), compared with children without these symptoms. We also found
      increased use of prescribed medication and most subtypes of health services.
      Current asthma symptoms and current eczema symptoms, but not current hay fever
      symptoms, increased the health service costs with at least ?300 per year per
      child. CONCLUSION: Children with eczema, asthma, and hay fever used health
      services and prescribed medication more than children without these diseases.

PMID- 27695365
TI  - Continuation rates, bleeding profile acceptability, and satisfaction of women
      using an oral contraceptive pill containing estradiol valerate and dienogest
      versus a progestogen-only pill after switching from an ethinylestradiol
      containing pill in a real-life setting: results of the CONTENT study.
AB  - BACKGROUND: Oral contraceptives are still associated with high discontinuation
      rates, despite their efficacy. There is a wide choice of oral contraceptives
      available, and the aim of this study was to assess continuation rates, bleeding
      profile acceptability, and the satisfaction of women in the first year of using a
      contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) versus a
      progestogen-only pill (POP) in a real-life setting after discontinuing an
      ethinylestradiol-containing pill. METHODS AND RESULTS: In this prospective,
      noninterventional, observational study, 3,152 patients were included for the
      efficacy analyses (n=2,558 women in the E2V/DNG group and n=592 in the POP group
      (two patients fulfilled the criteria of the efficacy population, but the used
      product was not known). Women had been taking an ethinylestradiol-containing pill
      >=3 months before deciding to switch to the E2V/DNG pill or a POP. Overall, 19.8%
      (n=506) of E2V/DNG users and 25.8% (n=153) of POP users discontinued their
      prescribed pill. The median time to discontinuation was 157.0 days and 127.5
      days, respectively. Time to discontinuation due to bleeding (P<0.0001) or other
      reasons (P=0.022) was significantly longer in the E2V/DNG group versus the POP
      group. The E2V/DNG pill was also associated with shorter (48.7% vs 44.1%),
      lighter (54% vs 46.1%), and less painful bleeding (91.1% vs 73.7%) and greater
      user satisfaction (80.7% vs 64.6%) than POP use, within 3-5 months after switch.
      CONCLUSION: The E2V/DNG pill was associated with higher rates of continuation,
      bleeding profile acceptability, and user satisfaction than POP use and may be an
      alternative option for women who are dissatisfied with their current pill.

PMID- 27695363
TI  - Atypical teratoid/rhabdoid tumors: challenges and search for solutions.
AB  - Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal central
      nervous system tumor commonly affecting children <3 years of age. It roughly
      constitutes 1%-2% of all pediatric central nervous system tumors. Recent data
      show that it is the most common malignant central nervous system tumor in
      children <6 months of age. Management of this aggressive tumor is associated with
      a myriad of diagnostic and therapeutic challenges. On the basis of radiology and
      histopathology alone, distinction of AT/RT from medulloblastoma or primitive
      neuroectodermal tumor is difficult, and hence this tumor has been commonly
      misdiagnosed as primitive neuroectodermal tumor for decades. Presence of a bulky
      heterogeneous solid-cystic mass with readily visible calcification and intratumor
      hemorrhage, occurring off-midline in children <3 years of age, should alert the
      radiologist toward the possibility of AT/RT. Presence of rhabdoid cells on
      histopathology and polyphenotypic immunopositivity for epithelial, mesenchymal,
      and neuroectodermal markers along with loss of expression of SMARCB1/INI1 or
      SMARCA4/BRG1 help in establishing a diagnosis of AT/RT. The optimal management
      comprises maximal safe resection followed by radiation therapy and multiagent
      intensive systemic chemotherapy. Gross total excision is difficult to achieve in
      view of the large tumor size and location and young age at presentation.
      Leptomeningeal spread is noted in 15%-30% of patients, and hence craniospinal
      irradiation followed by boost to tumor bed is considered standard in children
      older than 3 years. However, in younger children, craniospinal irradiation may
      lead to long-term neurocognitive and neuroendocrine sequel, and hence focal
      radiation therapy may be a pragmatic approach. In this age group, high-dose
      chemotherapy with autologous stem cell rescue may also be considered to defer
      radiation therapy, but this approach is also associated with significant
      treatment-related morbidity and mortality. Novel small molecule inhibitors hold
      promise in preclinical studies and should be considered in patients with relapsed
      or refractory tumor.

PMID- 27695366
TI  - Primary dysmenorrhea magnitude, associated risk factors, and its effect on
      academic performance: evidence from female university students in Ethiopia.
AB  - BACKGROUND: Primary dysmenorrhea (PD) is the most common gynecologic compliant
      among adolescent females. There is a wide variation in the estimate of PD, which
      ranges from 50% to 90%, and the disorder is the most common cause of work and
      school absenteeism in adolescent females. OBJECTIVE: To assess the prevalence and
      associated risk factors of PD among female university students and understand its
      effects on students' academic performance. METHODS: A cross-sectional study was
      employed in 440 research participants. A multistage stratified sampling technique
      was employed to select the study units. Structured and pretested self
      administered questionnaires were used and weight and height measurements were
      conducted. The severity of dysmenorrheal pain was assessed by using a verbal
      multidimensional scoring system and visual analog scale. The data were double
      entered in Epi Info version 3.1 and analyzed using SPSS version 17. Descriptive
      statistics, chi-square test, and logistic regression analysis were performed.
      RESULTS: A total of 440 students participated in this study. The prevalence of PD
      was 368 (85.4%). Of these, 123 (28.5%) had mild, 164 (38.1%) moderate, and 81
      (18.8%) severe primary dysmenorrheal pain. Among students with PD, 88.3% reported
      that PD had a negative effect on their academic performance. Of these, 80%
      reported school absence, 66.8% reported loss of class concentration, 56.3%
      reported class absence, 47.4% reported loss of class participation, 37.8%
      reported limited sport participation, 31.7% reported limitation in going out with
      friends, and 21% reported inability to do homework. Based on the multivariate
      logistic regression, PD was statistically significant with those who had lower
      monthly stipends, a history of attempt to lose weight, a history of depression or
      anxiety, disruption of social network of family, friends or people they love, who
      consumed more than four glasses of tea per day, who drunk one or more Coca-Cola
      or Pepsi per day, in nullipara, and students with a family history of
      dysmenorrhea. CONCLUSION: PD is more prevalent among female students attending
      university. It has a significant negative impact on students' academic
      performance. Thus, it needs medical attention. There are various identified
      associated risk factors and considering them in the management of the disorder is
      fundamental. It is also wise to recommend future studies to better identify risk
      factors for PD and lighten its effect on students' academic performance at a
      larger scale in the country.

PMID- 27695367
TI  - Simultaneous occlusion of three cilioretinal arteries following scleral buckling
      surgery under local anesthesia.
AB  - BACKGROUND: Cilioretinal artery (CRA) occlusions are rare in young patients. In
      these cases, the most commonly associated causes are considered to be the same as
      those implicated in central retina artery occlusions, such as vasculitic
      processes, migraine, cardiac disorder, and coagulation abnormality. The aim of
      this article was to report for the first time the medical records and
      investigational results of an unusual case of simultaneous occlusion of three
      CRAs after scleral buckling surgery under local anesthesia. METHODS: A complete
      ophthalmic examination, including color fundus image, fundus fluorescein
      angiography, optical coherence tomography, visual field, as well as systemic and
      laboratory assessments, was performed. RESULTS: A case of contemporaneous
      blockage of three CRAs after ab externo surgery for retinal detachment in a 29
      year-old Caucasian woman was reported. The interdisciplinary approach and the
      imaging results have allowed us the clinical definition of such a very rare case.
      CONCLUSION: Here, we reported that optical coherence tomography is an
      indispensable tool to better delineate the pathological process and follow
      atrophic changes in the macula, especially in cases in which fundus fluorescein
      angiography and systemic tests may be poorly informative.

PMID- 27695368
TI  - Progressive loss of vision caused by asymptomatic pituitary macroadenoma: role of
      OCT.
AB  - INTRODUCTION: Most pituitary adenomas are clinically inactive. In patients with
      long-standing compression of the optic chiasm, ganglion cells may undergo axonal
      degeneration. Spectral domain optical coherence tomography (SD-OCT) is able to
      identify retinal nerve fiber layer (RNFL) and ganglion cell loss in the retina.
      We present a case in which SD-OCT was used to diagnose an asymptomatic pituitary
      macroadenoma. CLINICAL CASE: A 48-year-old female presented with progressive
      vision loss in both eyes. SD-OCT identified atrophy of the ganglion cell and
      nerve layers, with preservation of outer layers bilaterally. Magnetic resonance
      imaging of the brain showed a pituitary macroadenoma. The pathological diagnosis
      was nonfunctioning adenoma. DISCUSSION: As macroadenomas enlarge, they can induce
      uncrossed axon loss, resulting in nasal field defects and reduced visual acuity.
      In these cases, there is atrophy of the nasal and temporal portions of the optic
      disc, thus occupying a horizontal band across the disc. SD-OCT is able to
      identify RNFL loss in eyes with band atrophy of the optic nerve, which correlates
      with visual field defects found in perimetry. SD-OCT is a useful tool to assess
      the structural and functional damage of ganglion cells. In our case the SD-OCT
      demonstrated a symmetrical loss of the RNFL and the ganglion cell layer in both
      eyes, indicating important optic nerve damage.

PMID- 27695369
TI  - A simple, wide bandwidth, biopotential amplifier to record pacemaker pulse
      waveform.
AB  - Reliable detection of pacemaker pulses is getting more and more important in
      electrocardiography (ECG) diagnosis. Many studies recommend ECG amplifiers with
      higher bandwidth to prevent errors. In the past, few pilot studies showed that
      analysis of pacemaker pulses waveform can enhance diagnosis (eg, lead failure and
      fractured wire), but they were carried out with inadequate instrumentations for
      clinical practice. Typically, pacemaker pulses last hundreds of microseconds,
      edges of pulses elapse in few microseconds, and amplitude may exhibit large
      variations from few millivolts to volts. Pulse waveforms change often and depend
      on pacemaker type and programming. A simple, biopotential amplifier made of a few
      off-the-shelf components is proposed. The circuit fulfills specifications for
      biopotential amplifiers and offers a large bandwidth (~1 MHz). Therefore, it is
      able to accurately record time course of pacemaker pulses and allows highly
      accurate pulse detection and timing. Signals can be easily displayed and acquired
      by means of a standard, battery-powered oscilloscope. Pacemaker pulse
      vectorcardiography can be obtained by using two or more, wideband channels. Some
      exemplificative waveforms recorded during patient's periodic medical examination
      are reported. The proposed circuit offers simultaneous conventional ECG signal as
      an additional output.

PMID- 27695370
TI  - Presence and consequence of tooth periapical radiolucency in patients with
      cirrhosis.
AB  - BACKGROUND: Periapical radiolucency is the radiographic sign of inflammatory bone
      lesions around the apex of the tooth. We determined the prevalence and predictors
      of periapical radiolucency in patients with cirrhosis and the association with
      systemic inflammation status and cirrhosis-related complications. METHODS: A
      total of 110 cirrhosis patients were consecutively enrolled. Periapical
      radiolucency was defined as the presence of radiolucency or widening of the
      periapical periodontal ligament space to more than twice the normal width.
      Predictors of periapical radiolucency and the association with systemic
      inflammation markers and cirrhosis-related complications were explored by
      univariable and multivariable logistic regression analyses. RESULTS: Periapical
      radiolucency was present in one or more teeth in 46% of the patients. Strong
      predictors were gross caries (odds ratio [OR] 3.12, 95% confidence interval [CI]
      1.43-6.79) and severe periodontitis (OR 3.98, 95% CI 1.04-15.20). Also old age
      (OR 1.10, 95% CI 1.01-1.19) and smoking (OR 3.24, 95% CI 1.02-17.62) were
      predictors. However, cirrhosis etiology (alcoholic vs nonalcoholic) or severity
      (Model of End-Stage Liver Disease score) were not predictors. The patients with
      periapical radiolucency had higher C-reactive protein (15.8 mg/L vs 8.1 mg/L,
      P=0.02) and lower albumin contents (25 g/L vs 28 g/L, P=0.04) than those without.
      Furthermore, the patients with periapical radiolucency had a higher prevalence of
      cirrhosis-related complications such as ascites, hepatic encephalopathy, and/or
      variceal bleeding (46% vs 27%, P=0.05). CONCLUSION: Periapical radiolucency is
      often present as an element of poor oral health status and likely has an adverse
      clinical significance, which should motivate diagnostic and clinical attention to
      the findings.

PMID- 27695371
TI  - Effects of gamma irradiation on the biomechanical properties of peroneus tendons.
AB  - PURPOSE: This study was designed to investigate the biomechanical properties of
      nonirradiated (NI) and irradiated (IR) peroneus tendons to determine if they
      would be suitable allografts, in regards to biomechanical properties, for
      anterior cruciate ligament reconstruction after a dose of 1.5-2.5 Mrad. METHODS:
      Seven pairs of peroneus longus (PL) and ten pairs of peroneus brevis (PB) tendons
      were procured from human cadavers. The diameter of each allograft was measured.
      The left side of each allograft was IR at 1.5-2.5 Mrad, whereas the right side
      was kept aseptic and NI. The allografts were thawed, kept wet with saline, and
      attached in a single-strand fashion to custom freeze grips using liquid nitrogen.
      A preload of 10 N was then applied and, after it had reached steady state, the
      allografts were pulled at 4 cm/sec. The parameters recorded were the displacement
      and force. RESULTS: The elongation at the peak load was 10.3+/-2.3 mm for the PB
      NI side and 13.5+/-3.3 mm for the PB IR side. The elongation at the peak load was
      17.4+/-5.3 mm for the PL NI side and 16.3+/-2.0 mm for the PL IR side. For PL,
      the ultimate load was 2,091.6+/-148.7 N for NI and 2,122.8+/-380.0 N for IR. The
      ultimate load for the PB tendons was 1,485.7+/-209.3 N for NI and 1,318.4+/-296.9
      N for the IR group. The ultimate stress calculations for PL were 90.3+/-11.3 MPa
      for NI and 94.8+/-21.0 MPa for IR. For the PB, the ultimate stress was 82.4+/
      19.0 MPa for NI and 72.5+/-16.6 MPa for the IR group. The structural stiffness
      was 216.1+/-59.0 N/mm for the NI PL and 195.7+/-51.4 N/mm for the IR side. None
      of these measures were significantly different between the NI and IR groups. The
      structural stiffness was 232.1+/-45.7 N/mm for the NI PB and 161.9+/-74.0 N/mm
      for the IR side, and this was the only statistically significant difference found
      in this study (P=0.034). CONCLUSION: Our statistical comparisons found no
      significant differences in terms of elongation, ultimate load, or ultimate stress
      between IR and NI PB and PL tendons. Only the PB structural stiffness was
      affected by irradiation. Thus, sterilizing allografts at 1.5-2.5 Mrad of gamma
      irradiation does not cause major alterations in the tendons' biomechanical
      properties while still providing a suitable amount of sterilization for anterior
      cruciate ligament reconstruction.

PMID- 27695372
TI  - The impact of shift work on the psychological and physical health of nurses in a
      general hospital: a comparison between rotating night shifts and day shifts.
AB  - BACKGROUND: Shift work is considered necessary to ensure continuity of care in
      hospitals and residential facilities. In particular, the night shift is one of
      the most frequent reasons for the disruption of circadian rhythms, causing
      significant alterations of sleep and biological functions that can affect
      physical and psychological well-being and negatively impact work performance.
      OBJECTIVES: The aim of this study was to highlight if shift work with nights, as
      compared with day work only, is associated with risk factors predisposing nurses
      to poorer health conditions and lower job satisfaction. METHODS: This cross
      sectional study was conducted from June 1, 2015 to July 31, 2015 in 17 wards of a
      general hospital and a residential facility of a northern Italian city. This
      study involved 213 nurses working in rotating night shifts and 65 in day shifts.
      The instrument used for data collection was the "Standard Shift Work Index,"
      validated in Italian. Data were statistically analyzed. RESULTS: The response
      rate was 86%. The nurses engaged in rotating night shifts were statistically
      significantly younger, more frequently single, and had Bachelors and Masters
      degrees in nursing. They reported the lowest mean score in the items of job
      satisfaction, quality and quantity of sleep, with more frequent chronic fatigue,
      psychological, and cardiovascular symptoms in comparison with the day shift
      workers, in a statistically significant way. CONCLUSION: Our results suggest that
      nurses with rotating night schedule need special attention due to the higher risk
      for both job dissatisfaction and undesirable health effects.

PMID- 27695374
TI  - Waterpipe Tobacco Smoking Among Dental Practitioners: Prevalence and Health
      Perceptions.
AB  - BACKGROUND: Waterpipe tobacco smoking prevalence, practice, and the associated
      health perceptions among dental practitioners have not been previously reported.
      This study aims to determine the prevalence of waterpipe smoking among dental
      practitioners and to evaluate their awareness of health hazards of waterpipe
      smoking, particularly the adverse effects on oral health. METHODS: This was a
      cross-sectional questionnaire-based survey among dental practitioners. Surveyed
      dental practitioners practiced dentistry in the holy city of Al-Madinah Al
      Munawarah, a city in the Central-Western Region of Saudi Arabia, and the study
      was conducted during March 2015. The questionnaire consisted of questions on
      demographic data, history and practices of tobacco use, and perceptions toward
      the health hazards of smoking. Dentists were approached at their work places and
      invited to participate. Descriptive statistics were used to describe the sample's
      demographic and smoking characteristics, while cross-tabulation and chi-square
      test were used to determine the statistical significance of association between
      the groups (P <= 0.05). RESULTS: One hundred dental practitioners participated in
      the survey, with 55 males and 45 females. Twenty-six percent indicated that they
      were waterpipe smokers. Male gender and cigarette smoking were the only factors
      to be significantly associated with waterpipe smoking (P = 0.008 and P = 0.000,
      respectively). Most participants stated that waterpipe smoking is harmful to
      health, and the most commonly reported health hazard was respiratory disease,
      which was reported by 81% of participants. CONCLUSIONS: Prevalence of waterpipe
      smoking among dental practitioners is comparable to adult populations but lower
      than younger populations of university students. Health awareness of dental
      practitioners regarding waterpipe smoking was judged to be insufficient.

PMID- 27695373
TI  - Police custody health care: a review of health morbidity, models of care and
      innovations within police custody in the UK, with international comparisons.
AB  - This paper is a scoping review of the available evidence regarding health care
      issues in police custody. It describes the types and prevalence of health
      disorders encountered in custody and provides an overview of current practice and
      recent innovations in police custody health care. In contrast to the health of
      prisoners, the health of police custody detainees has, until recently, received
      little academic or clinical attention. Studies on health care in police custody
      identified for this review are limited to a few geographical jurisdictions,
      including the UK, continental Europe, North America, and Australia. There are
      significant health concerns among police detainees including acute injury,
      chronic physical health problems, mental and cognitive disorders, and the risks
      associated with drug and alcohol intoxication or withdrawal. There is some
      evidence that deaths in police custody have reduced where attention has been paid
      to the latter issue. Police personnel continue to experience difficulties
      identifying detainees with health issues relevant to their safe detention, but
      research shows that the use of evidence-based screening tools improves detection
      of such morbidities. Innovations in police custody health care mainly relate to
      detainees with mental disorders, including improved identification of illness,
      timely access to mental health services, the protection of the rights of mentally
      disordered detainees, and the diversion of mentally disordered persons from the
      criminal justice system into appropriate health and social care interventions.
      There is a lack of rigorous research relating to interventions for physical
      health problems, protecting those at risk of substance withdrawal, and detainees
      with preexisting or peri-arrest injures. Research to improve the health of police
      custody detainees requires greater priority, focusing on case identification and
      service redesign to address high levels of morbidity and to facilitate health
      promotion and prevention activities.

PMID- 27695376
TI  - Distress prior to undergoing hematopoietic stem cell transplantation: demographic
      and symptom correlations and establishing a baseline.
AB  - BACKGROUND: Distress can arise from physical and/or psychosocial impairments and
      has been documented in patients after hematopoietic stem cell transplantation in
      the outpatient setting. It has not been evaluated in inpatients admitted to
      undergo the transplant, nor has potential correlations with length of hospital
      stay, physical function, and pain after receiving the transplant. OBJECTIVES: To
      measure distress in patients admitted to the hospital to undergo hematopoietic
      stem cell transplantation, and to evaluate potential correlations with length of
      hospital stay, physical function, pain, and depression/anxiety. METHODS: Eighty
      patients were given a questionnaire to report levels of distress and physical and
      psychosocial functioning. Hierarchical multiple regression analysis was used to
      test the relationship of demographic and transplant factors with length of stay
      (LOS), distress, presence of pain, and depression/anxiety. RESULTS: Patients
      reported pretransplant distress with an average score of 2.2 out of 10, and 16
      out of 80 patients reported clinically relevant distress. Pain was reported by
      42.5% of patients, and 28.8% reported depression/anxiety. Physical functioning
      was generally high. Distress was correlated with depression/anxiety (P-value
      <0.01) and pain (0.04) but not with LOS, physical function, patient age, or
      transplant type. CONCLUSION: LOS after receiving stem cell transplant was not
      related to pretransplant distress. Distress exists pretransplant but is generally
      low. Pain and the presence of depression/anxiety may be risk factors for
      distress. Measuring distress prior to transplant gives a baseline from which to
      measure changes, potentially leading to earlier intervention.

PMID- 27695375
TI  - Epigenetics and Cellular Metabolism.
AB  - Living eukaryotic systems evolve delicate cellular mechanisms for responding to
      various environmental signals. Among them, epigenetic machinery (DNA methylation,
      histone modifications, microRNAs, etc.) is the hub in transducing external
      stimuli into transcriptional response. Emerging evidence reveals the concept that
      epigenetic signatures are essential for the proper maintenance of cellular
      metabolism. On the other hand, the metabolite, a main environmental input, can
      also influence the processing of epigenetic memory. Here, we summarize the recent
      research progress in the epigenetic regulation of cellular metabolism and discuss
      how the dysfunction of epigenetic machineries influences the development of
      metabolic disorders such as diabetes and obesity; then, we focus on discussing
      the notion that manipulating metabolites, the fuel of cell metabolism, can
      function as a strategy for interfering epigenetic machinery and its related
      disease progression as well.

PMID- 27695377
TI  - Therapeutic and routine prophylactic properties of rFactor VIII Fc (efraloctocog
      alfa, Eloctate(r)) in hemophilia A.
AB  - rFVIIIFc (efraloctocog alfa, Eloctate(r)) is an extended half-life (EHL) factor
      VIII licensed for use in patients with hemophilia A for prophylaxis and treatment
      of bleeding and surgical episodes. Pharmacokinetic studies in adults have shown a
      mean 1.5-fold increase in half-life compared to full-length factor VIII. When
      compared to adults, the half-life is decreased by 8% in adolescents between 12
      and 17 years, by 18% in children 6 to <12 years, and by 33% in children between
      the ages of 2 and <6 years. There is a considerable interindividual variation in
      the prolongation of the half-life particularly in children and across the age
      groups, the range extending from no increase to a 2.5-fold increase. In addition
      to age, von willebrand factor (VWF) antigen level has demonstrated a significant
      impact on rFVIIIFc half-life, with higher VWF levels associated with greater
      prolongation of half-life. The pivotal and pediatric clinical trials have
      demonstrated the efficacy and safety of rFVIIIFc for use in regular prophylaxis
      and in management of bleeds and surgery. In these studies, just under half the
      participants showed a zero annualized bleed rate (ABR), and the median ABR (1.6
      in the pivotal study for the individualized prophylaxis arm) showed a further
      decrease in the extension study. On average, the patients required fewer
      infusions (reduced by at least a third), and the mean weekly consumption seems to
      be in keeping with standard recombinant factor VIII. EHL rFVIIIFc has made
      decreased infusion frequency a possibility. However, the interindividual
      variability in dose and infusion frequency highlights the need for a personalized
      approach based on individual patient's half-life and/or response to treatment.

PMID- 27695378
TI  - Improving self-regulation in adolescents: current evidence for the role of
      mindfulness-based cognitive therapy.
AB  - Mindfulness-based cognitive therapy (MBCT) was introduced in 1995 to address the
      problem of recurrent depression. MBCT is based on the notion that meditation
      helps individuals effectively deploy and regulate attention to effectively manage
      and treat a range of psychological symptoms, including emotional responses to
      stress, anxiety, and depression. Several studies demonstrate that mindfulness
      approaches can effectively reduce negative emotional reactions that result from
      and/or exacerbate psychiatric difficulties and exposure to stressors among
      children, adolescents, and their parents. Mindfulness may be particularly
      relevant for youth with maladaptive cognitive processes such as rumination.
      Clinical experience regarding the utility of mindfulness-based approaches,
      including MBCT, is being increasingly supported by empirical studies to optimize
      the effective treatment of youth with a range of challenging symptoms. This paper
      provides a description of MBCT, including mindfulness practices, theoretical
      mechanisms of action, and targeted review of studies in adolescents.

PMID- 27695379
TI  - Hyperglycemia: A Predictor of Death in Severe Head Injury Patients.
AB  - OBJECTIVES: Management of hyperglycemia during an acute sickness in adults is
      accompanied by improved outcomes. We have designed a prospective study with
      meticulous attention to exclude all diabetes patients by checking hemoglobin A1c
      (HbA1c or glycated hemoglobin) to avoid the ill-effects of hyperglycemia in
      patients with traumatic head injury admitted to the intensive care unit (ICU).
      METHODS: This prospective study included adults with traumatic primary brain
      injury with a Glasgow coma score of <=8 necessitating mechanical ventilation
      treated in the period 2012-2015. After screening 311 patients, 220 were included
      in the study. Both blood glucose and HbA1c levels of all the patients at
      admission, as well as blood glucose level after 72 hours, were obtained from the
      records. The patients were later grouped based on their admission blood glucose
      levels (<200 mg/dL or >=200 mg/dL). Injury severity score (ISS) was documented
      for every patient. As a final point, the outcomes were determined based on the
      hospital length of stay (HLS) and ICU length of stay (ILS), plusmortality rates.
      RESULTS: About 39% (n = 85) of patients were admitted with hyperglycemia during
      the study period. The mortality rate in patients with glucose >=200 mg/dL was
      65.8% (N = 56), against 23.7% (N = 32) in the group with glucose <200 mg/dL, with
      mortality rising as the blood glucose level increased (P = 0.014). CONCLUSIONS:
      We conclude that admission hyperglycemia is related with increased mortality rate
      in head injury patients, and comprehensive treatment of hyperglycemia can improve
      the outcome of severe head injury patients.

PMID- 27695380
TI  - Correction to "Barriers to Obtaining Sera and Tissue Specimens of African
      American Women for the Advancement of Cancer Research".
AB  - [This corrects the article DOI: 10.4137/CMWH.S34698.].

PMID- 27695381
TI  - Should a clinical rotation in hematology be mandatory for undergraduate medical
      students?
AB  - Clinical rotations form the foundation of medical education. Medical students in
      the UK are offered conventional rotations such as cardiology, surgery, and
      psychiatry as part of their undergraduate curriculum, but a rotation in
      hematology is not currently mandatory. This paper explores the benefits of a
      compulsory hematology rotation, and suggests recommendations for its
      implementation in UK medical school curricula.

PMID- 27695382
TI  - Factors associated with opioid overdose: a 10-year retrospective study of
      patients in a large integrated health care system.
AB  - OBJECTIVE: Opioid overdoses (ODs) have been increasing, and harm reduction
      efforts are a priority. The success of these efforts will be dependent on the
      identification of at-risk patients and improved access to the antidote naloxone.
      Therefore, to identify access to naloxone and factors associated with negative
      health outcomes, we conducted a retrospective study of patients with OD to
      identify those at highest risk of adverse outcomes and to assess the use of
      naloxone. METHODS: We conducted a study of electronic health records for patients
      admitted to the largest multihospital system in the region - the Geisinger Health
      System (GHS) for ODs - from April 2005 through March 2015. ODs were defined by
      International Classification of Diseases-9 codes (age range: 10-95 years).
      Bivariate analyses and multiple logistic regressions were conducted to identify
      pre-OD factors associated with adverse health outcomes post-OD. RESULTS: We
      identified 2,039 patients with one or more ODs, of whom 9.4% were deceased within
      12 months. Patient demographics suggest that patients with OD had a mean age of
      52 years, were not married (64%), and were unemployed (78%). Common comorbidities
      among patients with OD include cardiovascular disease (22%), diabetes (14%),
      cancer (13%), and the presence of one or more mental health disorders (35%). Few
      patients had a prescription order for naloxone (9%) after their OD. The majority
      of patients with OD were in proximity to GHS health care facilities, with 87%
      having a GHS primary care provider. In multiple logistic regressions, common
      predictors of adverse outcomes, including death, repeated ODs, frequent service
      use, and high service cost, were higher prescription opioid use, comorbid medical
      conditions, comorbid mental disorders, and concurrent use of other psychotropic
      medications. CONCLUSION: This study suggests opportunities for improving OD
      outcomes. Those who receive higher quantities of prescription opioids concurrent
      with other psychotropic medicines may need closer monitoring to avoid death,
      repeated OD events, higher service use, and higher service costs. Other
      opportunities for improving OD outcomes include the use of electronic health
      records to notify physicians of high-risk patients and updating of
      guidelines/operation manuals focused on the distribution of naloxone to those in
      highest need.

PMID- 27695383
TI  - Resampling-based multiple comparison procedure with application to point-wise
      testing with functional data.
AB  - In this paper we describe a coherent multiple testing procedure for correlated
      test statistics such as are encountered in functional linear models. The
      procedure makes use of two different p-value combination methods: the Fisher
      combination method and the Sidak correction-based method. P-values for Fisher's
      and Sidak's test statistics are estimated through resampling to cope with the
      correlated tests. Building upon these two existing combination methods, we
      propose the smallest p-value as a new test statistic for each hypothesis. The
      closure principle is incorporated along with the new test statistic to obtain the
      overall p-value and appropriately adjust the individual p-values. Furthermore, a
      shortcut version for the proposed procedure is detailed, so that individual
      adjustments can be obtained even for a large number of tests. The motivation for
      developing the procedure comes from a problem of point-wise inference with smooth
      functional data where tests at neighboring points are related. A simulation study
      verifies that the methodology performs well in this setting. We illustrate the
      proposed method with data from a study on the aerial detection of the spectral
      effect of below ground carbon dioxide leakage on vegetation stress via spectral
      responses.

PMID- 27695384
TI  - Movement analysis of free-grazing domestic ducks in Poyang Lake, China: a disease
      connection.
AB  - Previous work suggests domestic poultry are important contributors to the
      emergence and transmission of highly pathogenic avian influenza throughout Asia.
      In Poyang Lake, China, domestic duck production cycles are synchronized with
      arrival and departure of thousands of migratory wild birds in the area. During
      these periods, high densities of juvenile domestic ducks are in close proximity
      to migratory wild ducks, increasing the potential for the virus to be transmitted
      and subsequently disseminated via migration. In this paper, we use GPS
      dataloggers and dynamic Brownian bridge models to describe movements and habitat
      use of free-grazing domestic ducks in the Poyang Lake basin and identify specific
      areas that may have the highest risk of H5N1 transmission between domestic and
      wild birds. Specifically, we determine relative use by free-grazing domestic
      ducks of natural wetlands, which are the most heavily used areas by migratory
      wild ducks, and of rice paddies, which provide habitat for resident wild ducks
      and lower densities of migratory wild ducks. To our knowledge, this is the first
      movement study on domestic ducks, and our data show potential for free-grazing
      domestic ducks from farms located near natural wetlands to come in contact with
      wild waterfowl, thereby increasing the risk for disease transmission. This study
      provides an example of the importance of movement ecology studies in
      understanding dynamics such as disease transmission on a complicated landscape.

PMID- 27695386
TI  - Developing attributes for discrete choice experiments in health: a systematic
      literature review and case study of alcohol misuse interventions.
AB  - Discrete choice experiments (DCEs) become increasingly popular to value outcomes
      for health economic studies and gradually gain acceptance as an input into policy
      decisions. Developing attributes is a key aspect for the design of DCEs, as their
      results may misguide decision-makers if they are based on an inappropriate set of
      attributes. However, the area lacks guidance, and current health-related DCE
      studies vary considerably in their methods of attribute development, with the
      consequent danger of providing an unreliable input for policy decisions. The aim
      of this article is to inform the progress toward a more systematic approach to
      attribute development for DCE studies in health. A systematic review of the
      published health-related DCE literature was conducted to lay the foundations for
      a generic framework which was tested in a case study of alcohol misuse
      interventions. Four stages of a general attribute development process emerged:
      (i) raw data collection; (ii) data reduction; (iii) removing inappropriate
      attributes; and (iv) wording. The case study compared and contrasted a
      qualitative and mixed-methods approach for the development of attributes for DCEs
      in the area of alcohol misuse interventions. This article provides a reference
      point for the design of future DCE experiments in health.

PMID- 27695387
TI  - Parental smoking and children's anxieties: An appropriate strategy for health
      education?
AB  - While the prevalence of smoking has declined in the UK in recent years, class
      differentials in smoking behaviour have become more marked and smoking is
      increasingly recognised as a causal factor in inequalities in health. Health
      education initiatives to support both smoking cessation and to teach children
      about the health risks of smoking remain key initiatives in reducing health
      inequalities. However, teaching children about the risks of smoking and the
      impact of parental smoking in their health is not straightforward for children
      from backgrounds who are more likely to encounter smoking at home and in their
      local communities. These children have to reconcile the key messages taught at
      school and reinforced in smoking cessation campaigns with the knowledge that
      their parents and other family members smoke. In this paper we consider how
      children from smoking homes make sense of these education and health campaigns as
      observed by their parents, and the impact that this has on both parental smoking
      and relationships within the home. The paper thus seeks to challenge assumptions
      about the delivery of health education and the need to acknowledge family
      diversity.

PMID- 27695388
TI  - Exploring stories of occupational engagement in a regional secure unit.
AB  - This paper focuses on the occupational experiences of five men living within a
      forensic mental health unit over a year. This study used a descriptive
      qualitative case study methodology to explore the meaning and value placed on
      daily life (activities, occupations and routines), and how this changed over
      time. The men's stories showed a complex picture of their experiences of daily
      life. This study demonstrated the impact of the environment on the men and the
      ongoing challenge of the need to balance treatment/therapy with security demands
      and opportunities. Three interrelated themes were identified: (1) Power and
      Occupation; (2) Therapy or Punishment; (3) Occupational Opportunities within
      Restrictions. These findings serve as a reminder to clinical teams to reassess
      the value of occupations attributed by their patients and the impact of the
      secure environment, whilst also acknowledging the potential for occupations to
      have a negative impact on well-being.

PMID- 27695385
TI  - The Functional Overlap of Executive Control and Language Processing in
      Bilinguals.
AB  - The need to control multiple languages is thought to require domain-general
      executive control (EC) in bilinguals such that the EC and language systems become
      interdependent. However, there has been no systematic investigation into how and
      where EC and language processes overlap in the bilingual brain. If the concurrent
      recruitment of EC during bilingual language processing is domain-general and
      extends to non-linguistic EC, we hypothesize that regions commonly involvement in
      language processing, linguistic EC, and non-linguistic EC may be selectively
      altered in bilinguals compared to monolinguals. A conjunction of functional
      magnetic resonance imaging (fMRI) data from a flanker task with linguistic and
      nonlinguistic distractors and a semantic categorization task showed functional
      overlap in the left inferior frontal gyrus (LIFG) in bilinguals, whereas no
      overlap occurred in monolinguals. This research therefore identifies a neural
      locus of functional overlap of language and EC in the bilingual brain.

PMID- 27695389
TI  - Stable Isotopes Suggest Low Site Fidelity in Bar-headed Geese (Anser indicus) in
      Mongolia: Implications for Disease Transmission.
AB  - Population connectivity is an important consideration in studies of disease
      transmission and biological conservation, especially with regard to migratory
      species. Determining how and when different subpopulations intermingle during
      different phases of the annual cycle can help identify important geographical
      regions or features as targets for conservation efforts and can help inform our
      understanding of continental-scale disease transmission. In this study, stable
      isotopes of hydrogen and carbon in contour feathers were used to assess the
      degree of molt-site fidelity among Bar-headed Geese (Anser indicus) captured in
      north-central Mongolia. Samples were collected from actively molting Bar-headed
      Geese (n = 61), and some individual samples included both a newly grown feather
      (still in sheath) and an old, worn feather from the bird's previous molt (n =
      21). Although there was no difference in mean hydrogen isotope ratios for the old
      and new feathers, the isotopic variance in old feathers was approximately three
      times higher than that of the new feathers, which suggests that these birds use
      different and geographically distant molting locations from year to year. To
      further test this conclusion, online data and modeling tools from the isoMAP
      website were used to generate probability landscapes for the origin of each
      feather. Likely molting locations were much more widespread for old feathers than
      for new feathers, which supports the prospect of low molt-site fidelity. This
      finding indicates that population connectivity would be greater than expected
      based on data from a single annual cycle, and that disease spread can be rapid
      even in areas like Mongolia where Bar-headed Geese generally breed in small
      isolated groups.

PMID- 27695390
TI  - Using Phenomic Analysis of Photosynthetic Function for Abiotic Stress Response
      Gene Discovery.
AB  - Monitoring the photosynthetic performance of plants is a major key to
      understanding how plants adapt to their growth conditions. Stress tolerance
      traits have a high genetic complexity as plants are constantly, and unavoidably,
      exposed to numerous stress factors, which limits their growth rates in the
      natural environment. Arabidopsis thaliana, with its broad genetic diversity and
      wide climatic range, has been shown to successfully adapt to stressful conditions
      to ensure the completion of its life cycle. As a result, A. thaliana has become a
      robust and renowned plant model system for studying natural variation and
      conducting gene discovery studies. Genome wide association studies (GWAS) in
      restructured populations combining natural and recombinant lines is a
      particularly effective way to identify the genetic basis of complex traits. As
      most abiotic stresses affect photosynthetic activity, chlorophyll fluorescence
      measurements are a potential phenotyping technique for monitoring plant
      performance under stress conditions. This review focuses on the use of
      chlorophyll fluorescence as a tool to study genetic variation underlying the
      stress tolerance responses to abiotic stress in A. thaliana.

PMID- 27695391
TI  - Latent Class Analysis of Incomplete Data via an Entropy-Based Criterion.
AB  - Latent class analysis is used to group categorical data into classes via a
      probability model. Model selection criteria then judge how well the model fits
      the data. When addressing incomplete data, the current methodology restricts the
      imputation to a single, pre-specified number of classes. We seek to develop an
      entropy-based model selection criterion that does not restrict the imputation to
      one number of clusters. Simulations show the new criterion performing well
      against the current standards of AIC and BIC, while a family studies application
      demonstrates how the criterion provides more detailed and useful results than AIC
      and BIC.

PMID- 27695393
TI  - The Reliability of Naturalistic Observations of Social, Physical and Economic
      Environments of Bars.
AB  - Drinking in bars contributes to numerous public health problems, including
      violence and motor vehicle crashes. In order to formulate effective preventive
      interventions it is essential to identify which specific features of bar
      environments are related to increased risks. Unobtrusive ethnographic
      observations are one approach that has been used to characterize these features;
      however no studies have assessed reliability in a representative sample of bars.
      We performed brief scouting assessments in all 165 bars in six purposively
      selected California cities, followed by unobtrusive observations from a
      subsequent representative sample of 97 bars which were located in low and high
      bar density areas of the cities. Inter-rater reliability between two independent
      observers assessed individual item reliability, and principal components analyses
      assessed the reliability of a series of scales describing the physical, social,
      and economic characteristics of the bars. For the scouting assessment, items
      exhibited at least moderate reliability (kappa or r >= 0.40). For the unobtrusive
      observations, items assessing physical and economic environments (e.g., pool
      table present, kappa = 0.90; index beer cost, r = 0.82) had moderate to
      outstanding reliability (kappa or r > 0.80). Items describing the social
      environment generally had poorer reliability, though group aspects (e.g., patron
      count, r = 0.78; patron circulation, r = 0.64) had better reliability than
      individual behaviors (e.g., derogatory speech, kappa = 0.12). Scales constructed
      from specific sets of items exhibited modest reliability. The individual metrics
      and principal components we present will enable future studies seeking to
      disaggregate relationships between bar characteristics and public health
      problems.

PMID- 27695392
TI  - The metabolome 18 years on: a concept comes of age.
AB  - BACKGROUND: The term 'metabolome' was introduced to the scientific literature in
      September 1998. AIM AND KEY SCIENTIFIC CONCEPTS OF THE REVIEW: To mark its 18
      year-old 'coming of age', two of the co-authors of that paper review the genesis
      of metabolomics, whence it has come and where it may be going.

PMID- 27695394
TI  - Risk factors for complications after pharyngolaryngectomy with total
      esophagectomy.
AB  - BACKGROUND: Pharyngolaryngectomy with total esophagectomy (PLTE) is an effective
      surgical treatment for synchronous or metachronous hypopharyngeal or laryngeal
      cancer and thoracic esophageal cancer, although it is more invasive than
      esophagectomy and total pharyngolaryngectomy. The aim of this study was to
      identify risk factors for complications after PLTE. METHODS: From November 2002
      to December 2014, a total of 8 patients underwent PLTE at the Shizuoka Cancer
      Center Hospital, Shizuoka, Japan. We investigated the clinicopathological
      characteristics, surgical procedures, and postoperative complications of these
      patients. RESULTS: Of the 8 patients, 5 underwent one-stage PLTE and 3 underwent
      staged PLTE. There was no mortality in this study. Two cases of tracheal
      necrosis, two of anastomotic leakage, and one of ileus were observed as
      postoperative complications. Two patients who underwent one-stage PLTE with
      standard mediastinal lymph node dissection developed tracheal necrosis and severe
      anastomotic leakage. CONCLUSION: One-stage PLTE and standard mediastinal lymph
      node dissection were identified as the risk factors for severe postoperative
      complications. Staged PLTE or transhiatal esophagectomy should be considered when
      PLTE is performed and standard mediastinal lymph node dissection should be
      avoided when one-stage PLTE is performed with transthoracic esophagectomy.

PMID- 27695395
TI  - Coordination Dynamics in Cognitive Neuroscience.
AB  - Many researchers and clinicians in cognitive neuroscience hold to a modular view
      of cognitive function in which the cerebral cortex operates by the activation of
      areas with circumscribed elementary cognitive functions. Yet an ongoing paradigm
      shift to a dynamic network perspective is underway. This new viewpoint treats
      cortical function as arising from the coordination dynamics within and between
      cortical regions. Cortical coordination dynamics arises due to the unidirectional
      influences imposed on a cortical area by inputs from other areas that project to
      it, combined with the projection reciprocity that characterizes cortical
      connectivity and gives rise to reentrant processing. As a result, cortical
      dynamics exhibits both segregative and integrative tendencies and gives rise to
      both cooperative and competitive relations within and between cortical areas that
      are hypothesized to underlie the emergence of cognition in brains.

PMID- 27695396
TI  - Vascular Dysfunction in a Transgenic Model of Alzheimer's Disease: Effects of
      CB1R and CB2R Cannabinoid Agonists.
AB  - There is evidence of altered vascular function, including cerebrovascular, in
      Alzheimer's disease (AD) and transgenic models of the disease. Indeed
      vasoconstrictor responses are increased, while vasodilation is reduced in both
      conditions. beta-Amyloid (Abeta) appears to be responsible, at least in part, of
      alterations in vascular function. Cannabinoids, neuroprotective and anti
      inflammatory agents, induce vasodilation both in vivo and in vitro. We have
      demonstrated a beneficial effect of cannabinoids in models of AD by preventing
      glial activation. In this work we have studied the effects of these compounds on
      vessel density in amyloid precursor protein (APP) transgenic mice, line 2576, and
      on altered vascular responses in aortae isolated ring. First we showed increased
      collagen IV positive vessels in AD brain compared to control subjects, with a
      similar increase in TgAPP mice, which was normalized by prolonged oral treatment
      with the CB1/CB2 mixed agonist WIN 55,212-2 (WIN) and the CB2 selective agonist
      JWH-133 (JWH). In Tg APP mice the vasoconstriction induced by phenylephrine and
      the thromboxane agonist U46619 was significantly increased, and no change in the
      vasodilation to acetylcholine (ACh) was observed. Tg APP displayed decreased
      vasodilation to both cannabinoid agonists, which were able to prevent decreased
      ACh relaxation in the presence of Abeta. In summary, we have confirmed and
      extended the existence of altered vascular responses in Tg APP mice. Moreover,
      our results suggest that treatment with cannabinoids may ameliorate the vascular
      responses in AD-type pathology.

PMID- 27695397
TI  - A Personalized Multi-Channel FES Controller Based on Muscle Synergies to Support
      Gait Rehabilitation after Stroke.
AB  - It has been largely suggested in neuroscience literature that to generate a vast
      variety of movements, the Central Nervous System (CNS) recruits a reduced set of
      coordinated patterns of muscle activities, defined as muscle synergies. Recent
      neurophysiological studies have recommended the analysis of muscle synergies to
      finely assess the patient's impairment, to design personalized interventions
      based on the specific nature of the impairment, and to evaluate the treatment
      outcomes. In this scope, the aim of this study was to design a personalized multi
      channel functional electrical stimulation (FES) controller for gait training,
      integrating three novel aspects: (1) the FES strategy was based on healthy muscle
      synergies in order to mimic the neural solutions adopted by the CNS to generate
      locomotion; (2) the FES strategy was personalized according to an initial
      locomotion assessment of the patient and was designed to specifically activate
      the impaired biomechanical functions; (3) the FES strategy was mapped accurately
      on the altered gait kinematics providing a maximal synchronization between
      patient's volitional gait and stimulation patterns. The novel intervention was
      tested on two chronic stroke patients. They underwent a 4-week intervention
      consisting of 30-min sessions of FES-supported treadmill walking three times per
      week. The two patients were characterized by a mild gait disability (walking
      speed > 0.8 m/s) at baseline. However, before treatment both patients presented
      only three independent muscle synergies during locomotion, resembling two
      different gait abnormalities. After treatment, the number of extracted synergies
      became four and they increased their resemblance with the physiological muscle
      synergies, which indicated a general improvement in muscle coordination. The
      originally merged synergies seemed to regain their distinct role in locomotion
      control. The treatment benefits were more evident for one patient, who achieved a
      clinically important change in dynamic balance (Mini-Best Test increased from 17
      to 22) coupled with a very positive perceived treatment effect (GRC = 4). The
      treatment had started the neuro-motor relearning process also on the second
      subject, but twelve sessions were not enough to achieve clinically relevant
      improvements. This attempt to apply the novel theories of neuroscience research
      in stroke rehabilitation has provided promising results, and deserves to be
      further investigated in a larger clinical study.

PMID- 27695398
TI  - Integrative Signaling Networks of Membrane Guanylate Cyclases: Biochemistry and
      Physiology.
AB  - This monograph presents a historical perspective of cornerstone developments on
      the biochemistry and physiology of mammalian membrane guanylate cyclases (MGCs),
      highlighting contributions made by the authors and their collaborators. Upon
      resolution of early contentious studies, cyclic GMP emerged alongside cyclic AMP,
      as an important intracellular second messenger for hormonal signaling. However,
      the two signaling pathways differ in significant ways. In the cyclic AMP pathway,
      hormone binding to a G protein coupled receptor leads to stimulation or
      inhibition of an adenylate cyclase, whereas the cyclic GMP pathway dispenses with
      intermediaries; hormone binds to an MGC to affect its activity. Although the
      cyclic GMP pathway is direct, it is by no means simple. The modular design of the
      molecule incorporates regulation by ATP binding and phosphorylation. MGCs can
      form complexes with Ca2+-sensing subunits that either increase or decrease cyclic
      GMP synthesis, depending on subunit identity. In some systems, co-expression of
      two Ca2+ sensors, GCAP1 and S100B with ROS-GC1 confers bimodal signaling marked
      by increases in cyclic GMP synthesis when intracellular Ca2+ concentration rises
      or falls. Some MGCs monitor or are modulated by carbon dioxide via its conversion
      to bicarbonate. One MGC even functions as a thermosensor as well as a
      chemosensor; activity reaches a maximum with a mild drop in temperature. The
      complexity afforded by these multiple limbs of operation enables MGC networks to
      perform transductions traditionally reserved for G protein coupled receptors and
      Transient Receptor Potential (TRP) ion channels and to serve a diverse array of
      functions, including control over cardiac vasculature, smooth muscle relaxation,
      blood pressure regulation, cellular growth, sensory transductions, neural
      plasticity and memory.

PMID- 27695401
TI  - Differences in the Flexibility of Switching Learning Strategies and CREB
      Phosphorylation Levels in Prefrontal Cortex, Dorsal Striatum and Hippocampus in
      Two Inbred Strains of Mice.
AB  - Flexibility in using different learning strategies was assessed in two different
      inbred strains of mice, the C57BL/6 and DBA/2 strains. Mice were trained
      sequentially in two different Morris water maze protocols that tested their
      ability to switch their learning strategy to complete a new task after first
      being trained in a different task. Training consisted either of visible platform
      trials (cued training) followed by subsequent hidden platform trials (place
      training) or the reverse sequence (place training followed by cued training).
      Both strains of mice showed equivalent performance in the type of training (cued
      or place) that they received first. However, C57BL/6 mice showed significantly
      better performances than DBA/2 mice following the switch in training protocols,
      irrespective of the order of training. After completion of the switched training
      session, levels of cAMP response element-binding protein (CREB) and
      phosphorylated CREB (pCREB) were measured in the hippocampus, striatum and
      prefrontal cortex of the mice. Prefrontal cortical and hippocampal pCREB levels
      differed by strain, with higher levels found in C57BL/6 mice than in DBA/2 mice.
      No strain differences were observed in the medial or lateral region of the dorsal
      striatum. These findings indicate that the engagement (i.e., CREB signaling) of
      relevant neural structures may vary by the specific demands of the learning
      strategy, and this is closely tied to differences in the flexibility of C57BL/6
      and DBA/2 mice to switch their learning strategies when given a new task.

PMID- 27695399
TI  - NF-kappaB Pathways in the Pathogenesis of Multiple Sclerosis and the Therapeutic
      Implications.
AB  - Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)
      signaling pathways are involved in cell immune responses, apoptosis and
      infections. In multiple sclerosis (MS), NF-kappaB pathways are changed, leading
      to increased levels of NF-kappaB activation in cells. This may indicate a key
      role for NF-kappaB in MS pathogenesis. NF-kappaB signaling is complex, with many
      elements involved in its activation and regulation. Interestingly, current MS
      treatments are found to be directly or indirectly linked to NF-kappaB pathways
      and act to adjust the innate and adaptive immune system in patients. In this
      review, we will first focus on the intricacies of NF-kappaB signaling, including
      the activating pathways and regulatory elements. Next, we will theorize about the
      role of NF-kappaB in MS pathogenesis, based on current research findings, and
      discuss some of the associated therapeutic implications. Lastly, we will review
      four new MS treatments which interrupt NF-kappaB pathways-fingolimod,
      teriflunomide, dimethyl fumarate (DMF) and laquinimod (LAQ)-and explain their
      mechanisms, and the possible strategy for MS treatments in the future.

PMID- 27695402
TI  - Normal Evoked Response to Rapid Sequences of Tactile Pulses in Autism Spectrum
      Disorders.
AB  - Autism spectrum disorder (ASD) is a developmental disorder diagnosed
      behaviorally, with many documented neurophysiological abnormalities in cortical
      response properties. While abnormal sensory processing is not considered core to
      the disorder, most ASD individuals report sensory processing abnormalities. Yet,
      the neurophysiological correlates of these abnormalities have not been fully
      mapped. In the auditory domain, studies have shown that cortical responses in the
      early auditory cortex in ASD are abnormal in multiple ways. In particular, it has
      been shown that individuals with ASD have abnormal cortical auditory evoked
      responses to rapid, but not slow, sequences of tones. In parallel, there is
      substantial evidence of somatosensory processing abnormalities in ASD, including
      in the temporal domain. Here, we tested the somatosensory domain in ASD for
      abnormalities in rapid processing of tactile pulses, to determine whether
      abnormalities there parallel those observed in the auditory domain. Specifically,
      we tested the somatosensory cortex response to a sequence of two tactile pulses
      with different (short and long) temporal separation. We analyzed the responses in
      cortical space, in primary somatosensory cortex. As expected, we found no group
      difference in the evoked response to pulses with long (700 ms) temporal
      separation. Contrary to findings in the auditory domain, we also found no group
      differences in the evoked responses to the sequence with a short (200 ms)
      temporal separation. These results suggest that rapid temporal processing
      deficits in ASD are not generalized across multiple sensory domains, and are
      unlikely to underlie the behavioral somatosensory abnormalities observed in ASD.

PMID- 27695403
TI  - Novel Methods to Enhance Precision and Reliability in Muscle Synergy
      Identification during Walking.
AB  - Muscle synergies are hypothesized to reflect modular control of muscle groups via
      descending commands sent through multiple neural pathways. Recently, the number
      of synergies has been reported as a functionally relevant indicator of motor
      control complexity in individuals with neurological movement disorders. Yet the
      number of synergies extracted during a given activity, e.g., gait, varies within
      and across studies, even for unimpaired individuals. With no standardized methods
      for precise determination, this variability remains unexplained making
      comparisons across studies and cohorts difficult. Here, we utilize k-means
      clustering and intra-class and between-level correlation coefficients to
      precisely discriminate reliable from unreliable synergies. Electromyography (EMG)
      was recorded bilaterally from eight leg muscles during treadmill walking at self
      selected speed. Muscle synergies were extracted from 20 consecutive gait cycles
      using non-negative matrix factorization. We demonstrate that the number of
      synergies is highly dependent on the threshold when using the variance accounted
      for by reconstructed EMG. Beyond use of threshold, our method utilized a
      quantitative metric to reliably identify four or five synergies underpinning
      walking in unimpaired adults and revealed synergies having poor reproducibility
      that should not be considered as true synergies. We show that robust and
      unreliable synergies emerge similarly, emphasizing the need for careful analysis
      in those with pathology.

PMID- 27695404
TI  - Brain-Computer Interface Training after Stroke Affects Patterns of Brain-Behavior
      Relationships in Corticospinal Motor Fibers.
AB  - Background: Brain-computer interface (BCI) devices are being investigated for
      their application in stroke rehabilitation, but little is known about how
      structural changes in the motor system relate to behavioral measures with the use
      of these systems. Objective: This study examined relationships among diffusion
      tensor imaging (DTI)-derived metrics and with behavioral changes in stroke
      patients with and without BCI training. Methods: Stroke patients (n = 19) with
      upper extremity motor impairment were assessed using Stroke Impact Scale (SIS),
      Action Research Arm Test (ARAT), Nine-Hole Peg Test (9-HPT), and DTI scans. Ten
      subjects completed four assessments over a control period during which no
      training was administered. Seventeen subjects, including eight who completed the
      control period, completed four assessments over an experimental period during
      which subjects received interventional BCI training. Fractional anisotropy (FA)
      values were extracted from each corticospinal tract (CST) and transcallosal motor
      fibers for each scan. Results: No significant group by time interactions were
      identified at the group level in DTI or behavioral measures. During the control
      period, increases in contralesional CST FA and in asymmetric FA (aFA) correlated
      with poorer scores on SIS and 9-HPT. During the experimental period (with BCI
      training), increases in contralesional CST FA were correlated with improvements
      in 9-HPT while increases in aFA correlated with improvements in ARAT but with
      worsening 9-HPT performance; changes in transcallosal motor fibers positively
      correlated with those in the contralesional CST. All correlations p < 0.05
      corrected. Conclusion: These findings suggest that the integrity of the
      contralesional CST may be used to track individual behavioral changes observed
      with BCI training after stroke.

PMID- 27695406
TI  - Digit Position and Forces Covary during Anticipatory Control of Whole-Hand
      Manipulation.
AB  - Theoretical perspectives on anticipatory planning of object manipulation have
      traditionally been informed by studies that have investigated kinematics (hand
      shaping and digit position) and kinetics (forces) in isolation. This poses
      limitations on our understanding of the integration of such domains, which have
      recently been shown to be strongly interdependent. Specifically, recent studies
      revealed strong covariation of digit position and load force during the loading
      phase of two-digit grasping. Here, we determined whether such digit force
      position covariation is a general feature of grasping. We investigated the
      coordination of digit position and forces during five-digit whole-hand
      manipulation of an object with a variable mass distribution. Subjects were
      instructed to prevent object roll during the lift. As found in precision
      grasping, there was strong trial-to-trial covariation of digit position and
      force. This suggests that the natural variation of digit position that is
      compensated for by trial-to-trial variation in digit forces is a fundamental
      feature of grasp control, and not only specific to precision grasp. However, a
      main difference with precision grasping was that modulation of digit position to
      the object's mass distribution was driven predominantly by the thumb, with little
      to no modulation of finger position. Modulation of thumb position rather than
      fingers is likely due to its greater range of motion and therefore adaptability
      to object properties. Our results underscore the flexibility of the central
      nervous system in implementing a range of solutions along the digit force-to
      position continuum for dexterous manipulation.

PMID- 27695400
TI  - Precision Medicine in Multiple Sclerosis: Future of PET Imaging of Inflammation
      and Reactive Astrocytes.
AB  - Non-invasive molecular imaging techniques can enhance diagnosis to achieve
      successful treatment, as well as reveal underlying pathogenic mechanisms in
      disorders such as multiple sclerosis (MS). The cooperation of advanced multimodal
      imaging techniques and increased knowledge of the MS disease mechanism allows
      both monitoring of neuronal network and therapeutic outcome as well as the tools
      to discover novel therapeutic targets. Diverse imaging modalities provide
      reliable diagnostic and prognostic platforms to better achieve precision
      medicine. Traditionally, magnetic resonance imaging (MRI) has been considered the
      golden standard in MS research and diagnosis. However, positron emission
      tomography (PET) imaging can provide functional information of molecular biology
      in detail even prior to anatomic changes, allowing close follow up of disease
      progression and treatment response. The recent findings support three major
      neuroinflammation components in MS: astrogliosis, cytokine elevation, and
      significant changes in specific proteins, which offer a great variety of specific
      targets for imaging purposes. Regardless of the fact that imaging of astrocyte
      function is still a young field and in need for development of suitable imaging
      ligands, recent studies have shown that inflammation and astrocyte activation are
      related to progression of MS. MS is a complex disease, which requires
      understanding of disease mechanisms for successful treatment. PET is a precise
      non-invasive imaging method for biochemical functions and has potential to
      enhance early and accurate diagnosis for precision therapy of MS. In this review
      we focus on modulation of different receptor systems and inflammatory aspect of
      MS, especially on activation of glial cells, and summarize the recent findings of
      PET imaging in MS and present the most potent targets for new biomarkers with the
      main focus on experimental MS research.

PMID- 27695405
TI  - Structural Imaging Changes and Behavioral Correlates in Patients with Crohn's
      Disease in Remission.
AB  - Background: Crohn's disease (CD) is a subtype of inflammatory bowel disease
      caused by immune-mediated inflammation in the gastrointestinal tract. The extent
      of morphologic brain alterations and their associated cognitive and affective
      impairments remain poorly characterized. Aims: We used magnetic resonance imaging
      to identify structural brain differences between patients with Crohn's disease in
      remission compared to age-matched healthy controls and evaluated for structural
      behavioral correlates. Methods: Nineteen patients and 20 healthy, age-matched
      controls were recruited in the study. Group differences in brain morphometric
      measures and correlations between brain measures and performance on a cognitive
      task, the verbal fluency (VF) task, were examined. Correlations between brain
      measures and cognitive measures as well as self-reported measures of depression,
      personality, and affective scales were examined. Results: Patients showed
      significant cortical thickening in the left superior frontal region compared to
      controls. Significant group differences were observed in sub-cortical volume
      measures in both hemispheres. Investigation of brain-behavior correlations
      revealed significant group differences in the correlation between cortical
      surface area and VF performance, although behavioral performance was equivalent
      between the two groups. The left middle temporal surface area was a significant
      predictor of VF performance with controls showing a significant positive
      correlation between these measures, and patients showing the opposite effect.
      Conclusion: Our results indicate key differences in structural brain measures in
      patients with CD compared to controls. Additionally, correlation between brain
      measures and behavioral responses suggest there may be a neural basis to the
      alterations in patients' cognitive and affective responses.

PMID- 27695407
TI  - Preserved Self-Evaluation in Amnesia Supports Access to the Self through
      Introspective Computation.
AB  - Encounters with new people result in the extraction and storage in memory of both
      their external features, allowing us to recognize them later, and their internal
      traits, allowing us to better control our current interactions with them and
      anticipate our future ones. Just as we extract, encode, store, retrieve and
      update the representations of others so, too, do we process representations of
      ourselves. These representations, which rely on declarative memory, may be
      altered or cease to be accessible in amnesia. Nonetheless, studies of amnesic
      patients have yielded the surprising observation that memory impairments alone do
      not prevent patients from making accurate trait self-judgments. In this review
      article, we discuss prevailing explanations for preserved self-evaluation in
      amnesia and propose an alternative one, based on the concept of introspective
      computation. We also consider molecular and anatomical aspects of brain
      functioning that potentially support introspective computation.

PMID- 27695408
TI  - Resting-State Time-Varying Analysis Reveals Aberrant Variations of Functional
      Connectivity in Autism.
AB  - Recently, studies based on time-varying functional connectivity have unveiled
      brain states diversity in some neuropsychiatric disorders, such as schizophrenia
      and major depressive disorder. However, time-varying functional connectivity
      analysis of resting-state functional Magnetic Resonance Imaging (fMRI) have been
      rarely performed on the Autism Spectrum Disorder (ASD). Hence, we performed time
      varying connectivity analysis on resting-state fMRI data to investigate brain
      states mutation in ASD children. ASD showed an imbalance of connectivity state
      and aberrant ratio of connectivity with different strengths in the whole brain
      network, and decreased connectivity associated precuneus/posterior cingulate
      gyrus with medial prefrontal gyrus in default mode network. As compared to
      typical development children, weak relevance condition (the strength of a large
      number of connectivities in the state was less than means minus standard
      deviation of all connection strength) was maintained for a longer time between
      brain areas of ASD children, and ratios of weak connectivity in brain states
      varied dramatically in the ASD. In the ASD, the abnormal brain state might be
      related to repetitive behaviors and stereotypical interests, and macroscopically
      reflect disruption of gamma-aminobutyric acid at the cellular level. The
      detection of brain states based on time-varying functional connectivity analysis
      of resting-state fMRI might be conducive for diagnosis and early intervention of
      ASD before obvious clinical symptoms.

PMID- 27695410
TI  - Functional Equivalence of Imagined vs. Real Performance of an Inhibitory Task: An
      EEG/ERP Study.
AB  - Early neuroimaging and electrophysiological studies suggested that motor imagery
      recruited a different network than motor execution. However, several studies have
      provided evidence for the involvement of the same circuits in motor imagery
      tasks, in the absence of overt responses. The present study aimed to test whether
      imagined performance of a stop-signal task produces a similar pattern of motor
      related EEG activity than that observed during real performance. To this end, mu
      and beta event-related desynchronization (ERD) and the Lateralized Readiness
      Potential (LRP) were analyzed. The study also aimed to clarify the functional
      significance of the Stop-N2 and Stop-P3 event-related potential (ERPs)
      components, which were also obtained during both real and imagined performance.
      The results showed a common pattern of brain electrical activity, and with a
      similar time course, during covert performance and overt execution of the stop
      signal task: presence of LRP and Stop-P3 in the imagined condition and identical
      LRP onset, and similar mu and beta ERD temporal windows for both conditions.
      These findings suggest that a similar inhibitory network may be activated during
      both overt and covert execution of the task. Therefore, motor imagery may be
      useful to improve inhibitory skills and to develop new communicating systems for
      Brain-Computer Interface (BCI) devices based on inhibitory signals.

PMID- 27695409
TI  - Contribution of Neuroimaging Studies to Understanding Development of Human
      Cognitive Brain Functions.
AB  - Humans experience significant physical and mental changes from birth to
      adulthood, and a variety of perceptual, cognitive and motor functions mature over
      the course of approximately 20 years following birth. To deeply understand such
      developmental processes, merely studying behavioral changes is not sufficient;
      simultaneous investigation of the development of the brain may lead us to a more
      comprehensive understanding. Recent advances in noninvasive neuroimaging
      technologies largely contribute to this understanding. Here, it is very important
      to consider the development of the brain from the perspectives of "structure" and
      "function" because both structure and function of the human brain mature slowly.
      In this review, we first discuss the process of structural brain development,
      i.e., how the structure of the brain, which is crucial when discussing functional
      brain development, changes with age. Second, we introduce some representative
      studies and the latest studies related to the functional development of the
      brain, particularly for visual, facial recognition, and social cognition
      functions, all of which are important for humans. Finally, we summarize how brain
      science can contribute to developmental study and discuss the challenges that
      neuroimaging should address in the future.

PMID- 27695412
TI  - Eye Movements Affect Postural Control in Young and Older Females.
AB  - Visual information is used for postural stabilization in humans. However, little
      is known about how eye movements prevalent in everyday life interact with the
      postural control system in older individuals. Therefore, the present study
      assessed the effects of stationary gaze fixations, smooth pursuits, and saccadic
      eye movements, with combinations of absent, fixed and oscillating large-field
      visual backgrounds to generate different forms of retinal flow, on postural
      control in healthy young and older females. Participants were presented with
      computer generated visual stimuli, whilst postural sway and gaze fixations were
      simultaneously assessed with a force platform and eye tracking equipment,
      respectively. The results showed that fixed backgrounds and stationary gaze
      fixations attenuated postural sway. In contrast, oscillating backgrounds and
      smooth pursuits increased postural sway. There were no differences regarding
      saccades. There were also no differences in postural sway or gaze errors between
      age groups in any visual condition. The stabilizing effect of the fixed visual
      stimuli show how retinal flow and extraocular factors guide postural adjustments.
      The destabilizing effect of oscillating visual backgrounds and smooth pursuits
      may be related to more challenging conditions for determining body shifts from
      retinal flow, and more complex extraocular signals, respectively. Because the
      older participants matched the young group's performance in all conditions,
      decreases of posture and gaze control during stance may not be a direct
      consequence of healthy aging. Further research examining extraocular and retinal
      mechanisms of balance control and the effects of eye movements, during
      locomotion, is needed to better inform fall prevention interventions.

PMID- 27695411
TI  - Organelle-Specific Sensors for Monitoring Ca2+ Dynamics in Neurons.
AB  - Calcium (Ca2+) plays innumerable critical functions in neurons ranging from
      regulation of neurotransmitter release and synaptic plasticity to activity
      dependent transcription. Therefore, more than any other cell types, neurons are
      critically dependent on spatially and temporally controlled Ca2+ dynamics. This
      is achieved through an exquisite level of compartmentalization of Ca2+ storage
      and release from various organelles. The function of these organelles in the
      regulation of Ca2+ dynamics has been studied for decades using
      electrophysiological and optical methods combined with pharmacological and
      genetic alterations. Mitochondria and the endoplasmic reticulum (ER) are among
      the organelles playing the most critical roles in Ca2+ dynamics in neurons. At
      presynaptic boutons, Ca2+ triggers neurotransmitter release and synaptic
      plasticity, and postsynaptically, Ca2+ mobilization mediates long-term synaptic
      plasticity. To explore Ca2+ dynamics in live cells and intact animals, various
      synthetic and genetically encoded fluorescent Ca2+ sensors were developed, and
      recently, many groups actively increased the sensitivity and diversity of
      genetically encoded Ca2+ indicators (GECIs). Following conjugation with various
      signal peptides, these improved GECIs can be targeted to specific subcellular
      compartments, allowing monitoring of organelle-specific Ca2+ dynamics. Here, we
      review recent findings unraveling novel roles for mitochondria- and ER-dependent
      Ca2+ dynamics in neurons and at synapses.

PMID- 27695413
TI  - Adult Body Height Is a Good Predictor of Different Dimensions of Cognitive
      Function in Aged Individuals: A Cross-Sectional Study.
AB  - Background: Adult height, weight, and adiposity measures have been suggested by
      some studies to be predictors of depression, cognitive impairment, and dementia.
      However, the presence of confounding factors and the lack of a thorough
      neuropsychological evaluation in many of these studies have precluded a
      definitive conclusion about the influence of anthropometric measures in cognition
      and depression. In this study we aimed to assess the value of height, weight, and
      abdominal perimeter to predict cognitive impairment and depressive symptoms in
      aged individuals. Methods and Findings: Cross-sectional study performed between
      2010 and 2012 in the Portuguese general community. A total of 1050 participants
      were included in the study and randomly selected from local area health authority
      registries. The cohort was representative of the general Portuguese population
      with respect to age (above 50 years of age) and gender. Cognitive function was
      assessed using a battery of tests grouped in two dimensions: general executive
      function and memory. Two-step hierarchical multiple linear regression models were
      conducted to determine the predictive value of anthropometric measures in
      cognitive performance and mood before and after correction for possible
      confounding factors (gender, age, school years, physical activity, alcohol
      consumption, and smoking habits). We found single associations of weight, height,
      body mass index, abdominal perimeter, and age with executive function, memory and
      depressive symptoms. However, when included in a predictive model adjusted for
      gender, age, school years, and lifestyle factors only height prevailed as a
      significant predictor of general executive function (beta = 0.139; p < 0.001) and
      memory (beta = 0.099; p < 0.05). No relation was found between mood and any of
      the anthropometric measures studied. Conclusions and Relevance: Height is an
      independent predictor of cognitive function in late-life and its effects on the
      general and executive function and memory are independent of age, weight,
      education level, gender, and lifestyle factors. Altogether, our data suggests
      that modulators of adult height during childhood may irreversibly contribute to
      cognitive function in adult life and that height should be used in models to
      predict cognitive performance.

PMID- 27695414
TI  - Brooding Is Related to Neural Alterations during Autobiographical Memory
      Retrieval in Aging.
AB  - Brooding rumination is considered a central aspect of depression in midlife. As
      older people tend to review their past, rumination tendency might be particularly
      crucial in late life since it might hinder older adults to adequately evaluate
      previous events. We scanned 22 non-depressed older adults with varying degrees of
      brooding tendency with functional magnetic resonance imaging (MRI) while they
      performed the construction and elaboration of autobiographical memories.
      Behavioral findings demonstrate that brooders reported lower mood states, needed
      more time for memory construction and rated their memories as less detailed and
      less positive. On the neural level, brooding tendency was related to increased
      amygdala activation during the search for specific memories and reduced
      engagement of cortical networks during elaboration. Moreover, coupling patterns
      of the subgenual cingulate cortex with the hippocampus (HC) and the amygdala
      predicted details and less positive valence of memories in brooders. Our findings
      support the hypothesis that ruminative thinking interferes with the search for
      specific memories while facilitating the uncontrolled retrieval of negatively
      biased self-schemes. The observed neurobehavioral dysfunctions might put older
      people with brooding tendency at high risk for becoming depressed when reviewing
      their past. Training of autobiographical memory ability might therefore be a
      promising approach to increase resilience against depression in late-life.

PMID- 27695415
TI  - Turning Down the Thermostat: Modulating the Endocannabinoid System in Ocular
      Inflammation and Pain.
AB  - The endocannabinoid system (ECS) has emerged as an important regulator of both
      physiological and pathological processes. Notably, this endogenous system plays a
      key role in the modulation of pain and inflammation in a number of tissues. The
      components of the ECS, including endocannabinoids, their cognate enzymes and
      cannabinoid receptors, are localized in the eye, and evidence indicates that ECS
      modulation plays a role in ocular disease states. Of these diseases, ocular
      inflammation presents a significant medical problem, given that current clinical
      treatments can be ineffective or are associated with intolerable side-effects.
      Furthermore, a prominent comorbidity of ocular inflammation is pain, including
      neuropathic pain, for which therapeutic options remain limited. Recent evidence
      supports the use of drugs targeting the ECS for the treatment of ocular
      inflammation and pain in animal models; however, the potential for therapeutic
      use of cannabinoid drugs in the eye has not been thoroughly investigated at this
      time. This review will highlight evidence from experimental studies identifying
      components of the ocular ECS and discuss the functional role of the ECS during
      different ocular inflammatory disease states, including uveitis and corneal
      keratitis. Candidate ECS targeted therapies will be discussed, drawing on
      experimental results obtained from both ocular and non-ocular tissue(s), together
      with their potential application for the treatment of ocular inflammation and
      pain.

PMID- 27695416
TI  - Kidney Tissue Targeted Metabolic Profiling of Unilateral Ureteral Obstruction
      Rats by NMR.
AB  - Renal interstitial fibrosis is a common pathological process in the progression
      of kidney disease. A nuclear magnetic resonance (NMR) based metabolomic approach
      was used to analyze the kidney tissues of rats with renal interstitial fibrosis
      (RIF), induced by unilateral ureteral obstruction (UUO). The combination of a
      variety of statistical methods were used to screen out 14 significantly changed
      potential metabolites, which are related with multiple biochemical processes
      including amino acid metabolism, adenine metabolism, energy metabolism, osmolyte
      change and induced oxidative stress. The exploration of the contralateral kidneys
      enhanced the understanding of the disease, which was also supported by serum
      biochemistry and kidney histopathology results. In addition, the pathological
      parameters (clinical chemistry, histological and immunohistochemistry results)
      were correlated with the significantly changed differential metabolites related
      with RIF. This study showed that targeted tissue metabolomic analysis can be used
      as a useful tool to understand the mechanism of the disease and provide a novel
      insight in the pathogenesis of RIF.

PMID- 27695417
TI  - Antiplatelet Agents Inhibit the Generation of Platelet-Derived Microparticles.
AB  - Platelet microparticles (PMPs) contribute to thrombogenesis but the effects of
      antiplatelet drugs on PMPs generation is undefined. The present study
      investigated the cellular events regulating PMPs shedding, testing in vitro
      platelet agonists and inhibitors. Platelet-rich plasma from healthy subjects was
      stimulated with arachidonic acid (AA), U46619, collagen type-I (10 and 1.5
      MUg/mL), epinephrine, ADP or TRAP-6 and pre-incubated with acetylsalicylic acid
      (ASA, 100 and 10 MUmol/L), SQ-29,548, apyrase, PSB-0739, or eptifibatide. PMPs
      were detected by flow-cytometry using CD61 and annexin-V as fluorescent markers.
      Platelet agonists induced annexin V-positive PMPs shedding. The strongest
      response was to high concentration collagen. ADP-triggered PMPs shedding was dose
      independent. ASA reduced PMPs induced by AA- (645, 347-2946 vs. 3061, 446-4901
      PMPs/MUL; median ad range, n = 9, P < 0.001), collagen 10 MUg/mL (5317, 2027
      15935 vs. 10252, 4187-46316 PMPs/MUL; n = 13, P < 0.001), collagen 1.5 MUg/mL
      (1078, 528-2820 vs. 1465, 582-5948 PMPs/MUL; n = 21, P < 0.001) and TRAP-6 (2008,
      1621-2495 vs. 2840, 2404-3031 PMPs/MUL; n = 3, P < 0.01) but did not affect the
      response to epinephrine or ADP. The ADP scavenger apyrase reduced PMPs induced by
      U46619 (1256, 395-2908 vs. 3045, 1119-5494 PMPs/MUL, n = 6, P < 0.05), collagen
      1.5 MUg/mL (1006, 780-1309 vs. 2422, 1839-3494 PMPs/MUL, n = 3, P < 0.01) and
      TRAP-6 (904, 761-1224 vs. 2840, 2404-3031 PMPs/MUL, n = 3, P < 0.01). The TP
      receptor antagonist SQ-29,548 and the P2Y12 receptor antagonist PSB-0739 markedly
      inhibited PMPs induced by low doses of collagen. Except for high-dose collagen,
      eptifibatide abolished agonist-induced PMPs release. Both TXA2 generation and ADP
      secretion are required as amplifiers of PMP shedding. The crucial role of the
      fibrinogen receptor and the collagen receptor in PMPs generation, independently
      of platelet aggregation, was identified.

PMID- 27695419
TI  - Antioxidant Effect of Sericin in Brain and Peripheral Tissues of Oxidative Stress
      Induced Hypercholesterolemic Rats.
AB  - This study evaluated the antioxidant effect of crude sericin extract (CSE) from
      Antheraea assamensis in high cholesterol fed rats. Investigation was conducted by
      administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w.)/day of
      CSE for a period of 28 days. Experiments were conducted in 30 rats and were
      divided into five groups: normal control, high cholesterol fed (HCF), HCF + 0.065
      gm/kg b.w./day fenofibrate (FF), HCF + sericin 0.25 gm/kg b.w./day (LSD), and HCF
      + sericin 0.5 gm/kg b.w./day (HSD). In brain, heart, liver, serum, and kidney
      homogenates nitric oxide (NO), thiobarbituric acid reactive substances (TBARS),
      protein carbonyl content (PCC), superoxide dismutase, reduced glutathione (GSH)
      was measured. LSD treatment prevented the alterations in GSH and PCC levels in
      hypercholesterolemic (HyC) brain tissue homogenates of rats. CSE lowers the serum
      total cholesterol level in HyC rats by promoting fecal cholesterol (FC)
      excretion. CSE increases FC level by promoting inhibition of cholesterol
      absorption in intestine. The endogenous antioxidant reduced significantly and the
      oxidative stress marker TBARS level increases significantly in the peripheral
      tissue of HCF rats. However, the administration of LSD and HSD exhibited a good
      antioxidant activity by reducing the TBARS level and increasing the endogenous
      antioxidant in peripheral tissue. In addition, a histological examination
      revealed loss of normal liver and kidney architecture in cholesterol fed rats
      which were retained in sericin treated groups. The findings of this study
      suggested that CSE improves hypercholesterolemia in rats fed a HyC diet. Clinical
      relevance of this effect of CSE seems worthy of further studies.

PMID- 27695418
TI  - Impact of Cannabis, Cannabinoids, and Endocannabinoids in the Lungs.
AB  - Since the identification of cannabinoid receptors in the 1990s, a research field
      has been dedicated to exploring the role of the cannabinoid system in immunity
      and the inflammatory response in human tissues and animal models. Although the
      cannabinoid system is present and crucial in many human tissues, studying the
      impact of cannabinoids on the lungs is particularly relevant because of their
      contact with exogenous cannabinoids in the context of marijuana consumption. In
      the past two decades, the scientific community has gathered a large body of
      evidence supporting that the activation of the cannabinoid system alleviates pain
      and reduces inflammation. In the context of lung inflammation, exogenous and
      endogenous cannabinoids have shown therapeutic potential because of their
      inhibitory effects on immune cell recruitment and functions. On the other hand,
      cannabinoids were shown to be deleterious to lung function and to impact
      respiratory pathogen clearance. In this review, we present the existing data on
      the regulation of lung immunity and inflammation by phytocannabinoids, synthetic
      cannabinoids and endocannabinoids.

PMID- 27695420
TI  - Goggatomy: A Method for Opening Small Cuticular Compartments in Arthropods for
      Physiological Experiments.
AB  - Most sense organs of arthropods are ensconced in small exoskeletal compartments
      that hinder direct access to plasma membranes. We have developed a method for
      exposing live sensory and supporting cells in such structures. The technique uses
      a viscous light cured resin to embed and support the structure, which is then
      sliced with a sharp blade. We term the procedure a "goggatomy," from the Khoisan
      word for a bug, gogga. To demonstrate the utility of the method we show that it
      can be used to expose the auditory chordotonal organs in the second antennal
      segment and the olfactory receptor neurons in the third antennal segment of
      Drosophila melanogaster, preserving the transduction machinery. The procedure can
      also be used on other small arthropods, like mosquitoes and mites to expose a
      variety of cells.

PMID- 27695421
TI  - Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with
      Enhanced Insulin Sensitivity in Obese Middle-Aged Men.
AB  - Background: Obesity and aging are associated with increased oxidative stress,
      activation of stress and mitogen activated protein kinases (SAPK), and the
      development of insulin resistance and metabolic disease. In contrast, acute
      exercise also increases oxidative stress and SAPK signaling, yet is reported to
      enhance insulin sensitivity and reduce the risk of metabolic disease. This study
      explored this paradox by investigating the effect of a single session of high
      intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin
      protein signaling in eleven middle-aged obese men. Methods: Participants
      completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after
      HIIE (4 * 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1-3 weeks.
      Results: Irrespective of exercise-induced changes to redox status, insulin
      stimulation both at rest and after HIIE similarly increased plasma superoxide
      dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and
      significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling
      pathways of p38 MAPK, NF-kappaB p65, and JNK, and the distal insulin signaling
      protein AS160Ser588, were activated with insulin stimulation at rest and to a
      greater extent with insulin stimulation after a prior bout of HIIE. Higher
      insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD
      activity, JNK, p38 MAPK and NF-kappaB phosphorylation (r = 0.63, r = 0.71, r =
      0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role
      for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake
      which may contribute to the enhancement of insulin sensitivity in obese men 3 h
      after HIIE.

PMID- 27695422
TI  - Intermittent Hypoxia Influences Alveolar Bone Proper Microstructure via Hypoxia
      Inducible Factor and VEGF Expression in Periodontal Ligaments of Growing Rats.
AB  - Intermittent hypoxia (IH) recapitulates morphological changes in the
      maxillofacial bones in children with obstructive sleep apnea (OSA). Recently, we
      found that IH increased bone mineral density (BMD) in the inter-radicular
      alveolar bone (reflecting enhanced osteogenesis) in the mandibular first molar
      (M1) region in the growing rats, but the underlying mechanism remains unknown. In
      this study, we focused on the hypoxia-inducible factor (HIF) pathway to assess
      the effect of IH by testing the null hypothesis of no significant differences in
      the mRNA-expression levels of relevant factors associated with the HIF pathway,
      between control rats and growing rats with IH. To test the null hypothesis, we
      investigated how IH enhances mandibular osteogenesis in the alveolar bone proper
      with respect to HIF-1alpha and vascular endothelial growth factor (VEGF) in
      periodontal ligament (PDL) tissues. Seven-week-old male Sprague-Dawley rats were
      exposed to IH for 3 weeks. The microstructure and BMD in the alveolar bone proper
      of the distal root of the mandibular M1 were evaluated using micro-computed
      tomography (micro-CT). Expression of HIF-1alpha and VEGF mRNA in PDL tissues were
      measured, whereas osteogenesis was evaluated by measuring mRNA levels for
      alkaline phosphatase (ALP) and bone morphogenetic protein-2 (BMP-2). The null
      hypothesis was rejected: we found an increase in the expression of all of these
      markers after IH exposure. The results provided the first indication that IH
      enhanced osteogenesis of the mandibular M1 region in association with PDL
      angiogenesis during growth via HIF-1alpha in an animal model.

PMID- 27695423
TI  - Resveratrol Supplementation Did Not Improve Cognition in Patients with
      Schizophrenia: Results from a Randomized Clinical Trial.
AB  - BACKGROUND: Schizophrenia (SZ) is associated with psychotic experiences and
      cognitive deficits. Therefore, cognitive function is one of the most critical
      determinants of quality of life in this pathology. Resveratrol has been related
      to neuroprotective action, but there are no studies evaluating resveratrol in SZ.
      The objective of this study was to determine the efficacy of resveratrol
      supplementation on cognition in individuals with SZ. METHODS: This is a 1-month
      randomized, double-blind, and controlled trial (NCT 02062190), in which 19 men
      with diagnosis of SZ, aged 18-65 years, were assigned to a resveratrol
      supplementation group (200 mg) or placebo group (200 mg), with a 1-month follow
      up. Applying a series of cognitive tests assessed neuropsychology performance
      (Hopkins Verbal Learning Test, Stroop Color and Word Test, and Weschler Adult
      Intelligence Scale) and Brief Psychiatric Rating Scale assessed psychopathology
      severity. RESULTS: There were no significant improvement in neuropsychology
      performance (episodic memory, working memory, attention and concentration
      capacity, inhibitory control, interference measures, selective attention, and
      mental flexibility) and psychopathology severity after 1 month of resveratrol
      supplementation (P > 0.05). CONCLUSION: In conclusion, we have shown that 1 month
      of a resveratrol supplementation (200 mg/day) did not improve episodic memory,
      working memory, attention and concentration capacity, inhibitory control,
      interference measures, selective attention, and mental flexibility as compared
      with placebo in patients with SZ.

PMID- 27695424
TI  - Being Moved by Unfamiliar Sad Music Is Associated with High Empathy.
AB  - The paradox of enjoying listening to music that evokes sadness is yet to be fully
      understood. Unlike prior studies that have explored potential explanations
      related to lyrics, memories, and mood regulation, we investigated the types of
      emotions induced by unfamiliar, instrumental sad music, and whether these
      responses are consistently associated with certain individual difference
      variables. One hundred and two participants were drawn from a representative
      sample to minimize self-selection bias. The results suggest that the emotional
      responses induced by unfamiliar sad music could be characterized in terms of
      three underlying factors: Relaxing sadness, Moving sadness, and Nervous sadness.
      Relaxing sadness was characterized by felt and perceived peacefulness and
      positive valence. Moving sadness captured an intense experience that involved
      feelings of sadness and being moved. Nervous sadness was associated with felt
      anxiety, perceived scariness and negative valence. These interpretations were
      supported by indirect measures of felt emotion. Experiences of Moving sadness
      were strongly associated with high trait empathy and emotional contagion, but not
      with other previously suggested traits such as absorption or nostalgia-proneness.
      Relaxing sadness and Nervous sadness were not significantly predicted by any of
      the individual difference variables. The findings are interpreted within a
      theoretical framework of embodied emotions.

PMID- 27695425
TI  - ACC Neuro-over-Connectivity Is Associated with Mathematically Modeled Additional
      Encoding Operations of Schizophrenia Stroop-Task Performance.
AB  - Functional magnetic resonance imaging at 7.0 Tesla was undertaken among
      Schizophrenia participants (Sz), and clinical (major mood disorder; MDD) and
      healthy controls (HC), during performance of the Stoop task. Stroop conditions
      included congruent and incongruent word color items, color-only items, and word
      only items. Previous modeling results extended to this most widely used selective
      attention task. All groups executed item-encoding operations (subprocesses of the
      item encoding process) at the same rate (performance accuracy being similarly
      high throughout), thus displaying like processing capacity; Sz participants,
      however, employed more subprocesses for item completions than did the MDD
      participants, who in turn used more subprocesses than the HC group. The reduced
      efficiency in deploying cognitive-workload capacity among the Sz participants was
      paralleled by more diffuse neuroconnectivity (Blood-Oxygen-Level-Dependent co
      activation) with the anterior cingulate cortex (ACC) (Broadman Area 32),
      spreading away from this encoding-intensive region; and by less evidence of
      network dissociation across Stroop conditions. Estimates of cognitive work done
      to accomplish item completion were greater for the Sz participants, as were
      estimates of entropy in both the modeled trial-latency distribution, and its
      associated neuro-circuitry. Findings are held to be symptom and assessment
      significant, and to have potential implications for clinical intervention.

PMID- 27695427
TI  - Editorial: The Psychology of Magic and the Magic of Psychology.

PMID- 27695426
TI  - An Extension of the Procedural Deficit Hypothesis from Developmental Language
      Disorders to Mathematical Disability.
AB  - Mathematical disability (MD) is a neurodevelopmental disorder affecting math
      abilities. Here, we propose a new explanatory account of MD, the procedural
      deficit hypothesis (PDH), which may further our understanding of the disorder.
      According to the PDH of MD, abnormalities of brain structures subserving the
      procedural memory system can lead to difficulties with math skills learned in
      this system, as well as problems with other functions that depend on these brain
      structures. This brain-based account is motivated in part by the high comorbidity
      between MD and language disorders such as dyslexia that may be explained by the
      PDH, and in part by the likelihood that learning automatized math skills should
      depend on procedural memory. Here, we first lay out the PDH of MD, and present
      specific predictions. We then examine the existing literature for each
      prediction, while pointing out weaknesses and gaps to be addressed by future
      research. Although we do not claim that the PDH is likely to fully explain MD, we
      do suggest that the hypothesis could have substantial explanatory power, and that
      it provides a useful theoretical framework that may advance our understanding of
      the disorder.

PMID- 27695428
TI  - Punctuation and Implicit Prosody in Silent Reading: An ERP Study Investigating
      English Garden-Path Sentences.
AB  - This study presents the first two ERP reading studies of comma-induced effects of
      covert (implicit) prosody on syntactic parsing decisions in English. The first
      experiment used a balanced 2 * 2 design in which the presence/absence of commas
      determined plausibility (e.g., John, said Mary, was the nicest boy at the party
      vs. John said Mary was the nicest boy at the party). The second reading
      experiment replicated a previous auditory study investigating the role of overt
      prosodic boundaries in closure ambiguities (Pauker et al., 2011). In both
      experiments, commas reliably elicited CPS components and generally played a
      dominant role in determining parsing decisions in the face of input ambiguity.
      The combined set of findings provides further evidence supporting the claim that
      mechanisms subserving speech processing play an active role during silent
      reading.

PMID- 27695429
TI  - Does Loneliness Necessarily Lead to a Decrease in Prosocial Behavior? The Roles
      of Gender and Situation.
AB  - Although, previous studies show overwhelming evidence that loneliness is
      negatively correlated with prosocial behavior, some theories and research have
      implied that under certain situations, loneliness plays a positive role in an
      individual's social functioning. The two studies reported in this article
      examined loneliness and its associations with prosocial behavior in Chinese
      adults using subjective reporting and experimental design. Study 1 examined 305
      Chinese adults (175 males) using the Social and Emotional Loneliness Scale for
      Adults and the Prosocial Tendencies Measure to evaluate their loneliness and
      prosocial tendencies. The results showed that loneliness was negatively
      associated with all prosocial tendencies except the public prosocial tendency.
      Study 2 examined 177 Chinese adults (61 males) using an experimental design and
      found that only lonely women in public situations expressed a greater willingness
      to help. The results also suggest that loneliness may play a positive role in the
      social functioning of individuals under certain conditions. The function of
      loneliness and the implications of the association between loneliness and
      prosocial behavior are discussed.

PMID- 27695431
TI  - Semantic Richness Effects in Syntactic Classification: The Role of Feedback.
AB  - Words with richer semantic representations are recognized faster across a range
      of lexical processing tasks. The most influential account of this finding is
      based on the idea that semantic richness effects are mediated by feedback from
      semantic-level to lower-level representations. In an earlier lexical decision
      study, Yap et al. (2015) tested this claim by examining the joint effects of
      stimulus quality and four semantic richness dimensions (imageability, number of
      features, semantic neighborhood density, semantic diversity). The results of that
      study showed that joint effects of stimulus quality and richness were generally
      additive, consistent with the idea that semantic feedback does not typically
      reach the earliest levels of representation in lexical decision. The present
      study extends this earlier work by investigating the joint effects of stimulus
      quality and the same four semantic richness dimensions on syntactic
      classification performance (is this a noun or verb?), which places relatively
      more emphasis on semantic processing. Additive effects of stimulus quality and
      richness were found for two of the four targeted dimensions (concreteness, number
      of features) while semantic neighborhood density and semantic diversity did not
      seem to influence syntactic classification response times. These findings provide
      further support against the view that semantic information reaches early letter
      level processes.

PMID- 27695430
TI  - Action Sounds Modulate Arm Reaching Movements.
AB  - Our mental representations of our body are continuously updated through
      multisensory bodily feedback as we move and interact with our environment.
      Although it is often assumed that these internal models of body-representation
      are used to successfully act upon the environment, only a few studies have
      actually looked at how body-representation changes influence goal-directed
      actions, and none have looked at this in relation to body-representation changes
      induced by sound. The present work examines this question for the first time.
      Participants reached for a target object before and after adaptation periods
      during which the sounds produced by their hand tapping a surface were spatially
      manipulated to induce a representation of an elongated arm. After adaptation,
      participants' reaching movements were performed in a way consistent with having a
      longer arm, in that their reaching velocities were reduced. These kinematic
      changes suggest auditory-driven recalibration of the somatosensory representation
      of the arm morphology. These results provide support to the hypothesis that one's
      represented body size is used as a perceptual ruler to measure objects' distances
      and to accordingly guide bodily actions.

PMID- 27695432
TI  - The Effect of Number and Presentation Order of High-Constraint Sentences on
      Second Language Word Learning.
AB  - This paper presents the results of an experiment that investigated the effects of
      number and presentation order of high-constraint sentences on semantic processing
      of unknown second language (L2) words (pseudowords) through reading. All
      participants were Chinese native speakers who learned English as a foreign
      language. In the experiment, sentence constraint and order of different
      constraint sentences were manipulated in English sentences, as well as L2
      proficiency level of participants. We found that the number of high-constraint
      sentences was supportive for L2 word learning except in the condition in which
      high-constraint exposure was presented first. Moreover, when the number of high
      constraint sentences was the same, learning was significantly better when the
      first exposure was a high-constraint exposure. And no proficiency level effects
      were found. Our results provided direct evidence that L2 word learning benefited
      from high quality language input and first presentations of high quality language
      input.

PMID- 27695433
TI  - "Female Preponderance" of Depression in Non-clinical Populations: A Meta-Analytic
      Study.
AB  - Clinical observations and research suggest a female preponderance in major
      depressive disorder. However, it is unclear whether a similar gender difference
      is found for the reporting of depressive symptoms in non-clinical populations.
      The present meta-analysis was conducted to address this issue. We searched for
      published papers targeting non-clinical populations in which the 21-item Beck
      Depression Inventory (BDI) was used. Eighty-four papers (91 studies) published
      between 1977 and 2014 were included in the final meta-analysis, which comprised
      23,579 males and 29,470 females. Females in the general population reported
      higher level of depressive symptoms than males (d = -0.187, corresponding to
      1.159 points in the 21-item BDI). This pattern was not found to influence by
      years of publication, socioeconomic status, or version of the BDI used. Using age
      group as a moderator, studies with adolescents and young adults were found to
      show a smaller effect size than studies with older participants. Our results
      appear to confirm the "female preponderance" in the level of self-report
      depressive symptoms in the general population, and support the social gender role
      theory in explaining gender difference over biological susceptibility theory and
      evolutionary theory.

PMID- 27695434
TI  - Neural Mechanisms of Dorsal and Ventral Visual Regions during Text Reading.
AB  - When reading a narrative text, both the dorsal and ventral visual systems are
      activated. To illustrate the patterns of interactions between the dorsal and
      ventral visual systems in text reading, we conducted analyses of functional
      connectivity (FC) and effective connectivity (EC) in a left-hemispheric network
      for reading-driven functional magnetic resonance imaging (fMRI) and resting-state
      fMRI (rs-fMRI) data. In reading-driven fMRI (Experiment 1), we found significant
      FCs among the left middle frontal gyrus (MFG), the left intraparietal sulcus
      (IPS), and the visual word form area (VWFA), and there were top-down effects from
      the left MFG to the left IPS, from the left MFG to the VWFA, and from the left
      IPS to the VWFA. In rs-fMRI (Experiment 2), we identified FCs and ECs for MFG-IPS
      and IPS-VWFA connections. In addition, the brain-behavior relationship in resting
      states showed that the dorsal connection was more associated with reading fluency
      relative to lexical decision. The combination of two experiments revealed that
      the MFG-IPS and the VWFA-IPS connections were shared connections both in reading
      driven fMRI and rs-fMRI, and that the MFG-VWFA was specific connectivity in
      reading-driven fMRI. These results suggest that top-down effects from the dorsal
      visual system to ventral visual system play an important role in text reading.

PMID- 27695435
TI  - "PHE in Action": Development and Modeling of an Intervention to Improve Patient
      Engagement among Older Adults.
AB  - The increasing prevalence of chronic conditions among older adults constitutes a
      major public health problem. Thus, changes in lifestyles are required to prevent
      secondary conditions and sustain good care practices. While patient engagement
      received great attention in the last years as key strategy to solve this issue,
      to date no interventions exist to sustain the engagement of older chronic
      patients toward their health management. This study describes the design,
      development, and optimization of PHEinAction, a theoretically-driven intervention
      program to increase patient engagement in older chronic populations and
      consequently to foster healthy changes that can help reduce risks of health
      problems. The development process followed the UK Medical Research Council's
      (MRC) guidelines and involved selecting the theoretical base for the
      intervention, identifying the relevant evidence-based literature, and conducting
      exploratory research to qualitatively evaluate program's feasibility,
      acceptability, and comprehension. The result was a user-endorsed intervention
      designed to improve older patients' engagement in health management based on the
      theoretical framework of the Patient Health Engagement (PHE) model. The
      intervention program, which emerged from this process, consisted of 2 monthly
      face-to-face 1-h sessions delivered by a trained facilitator and one brief
      telephonic consultation, and aimed to facilitate a range of changes for patient
      engagement (e.g., motivation to change, health information seeking and use,
      emotional adjustment, health behaviors planning). PHEinAction is the first
      example of a theoretically-based patient engagement intervention designed for
      older chronic targets. The intervention program is based on psychological theory
      and evidence; it facilitates emotional, psychological, and behavioral processes
      to support patient engagement and lifestyle change and maintenance. It provides
      estimates of the extent to which it could help high-risk groups engage in
      effective health management and informs future trials.

PMID- 27695436
TI  - Understanding the Relationship between Rainstorm-Related Experiences and PTSD
      among Chinese Adolescents after Rainstorm Disaster: The Roles of Rumination and
      Social Support.
AB  - Posttraumatic stress disorder (PTSD) is prevalent among adolescents following
      natural disasters, and the trauma experiences represent a critical risk factor
      for PTSD. Nevertheless, the underlying mechanism of adolescents' PTSD following
      trauma experiences remains unclear. Rumination appears to be a mediating factor
      between trauma experiences and PTSD, and social support may moderate this
      mediating relationship between trauma experiences, rumination, and PTSD, but few
      studies have examined these assumptions. Thus, this study aimed to assess the
      mediating role of rumination and the moderating role of social support in the
      relationship between rainstorm-related experiences and PTSD among adolescents,
      following a rainstorm in China. Nine hundred and fifty-one middle school students
      completed self-report questionnaires, and structural equation modeling was
      conducted to examine the potential moderated mediation effect. Rainstorm-related
      experiences had a direct and positive effect on PTSD, and also indirectly
      influenced PTSD via rumination. Moreover, social support work to buffer the
      direct effect of rainstorm-related experiences on PTSD, but not the effect of
      rumination on PTSD. Implications for clinical practice and research are discussed
      along with study limitations.

PMID- 27695437
TI  - Determinants for a Successful Semont Maneuver: An In vitro Study with a
      Semicircular Canal Model.
AB  - OBJECTIVE: To evaluate the effect of time between the movements/steps, angle of
      body movements as well as the angular velocity of the maneuvers in an in vitro
      model of a semicircular canal (SCC) to improve the efficacy of the Semont
      maneuver (SM) in benign paroxysmal positional vertigo. MATERIALS AND METHODS:
      Semont maneuvers were performed on an in vitro SCC model. Otoconia trajectories
      were captured by a video camera. The effects of time between the movements,
      angles of motion (0 degrees , 10 degrees , 20 degrees , and 30 degrees  below the
      horizontal line), different angular velocities (90, 135, 180 degrees /s), and
      otoconia size (36 and 50 MUm) on the final position of the otoconia in the SCC
      were tested. RESULTS: Without extension of the movements beyond the horizontal,
      the in vitro experiments (with particles corresponding to 50 MUm diameter) did
      not yield successful canalith repositioning. If the movements were extended by 20
      degrees  beyond the horizontal position, SM were successful with resting times of
      at least 16 s. For larger extension angles, the required time decreased. However,
      for smaller particles (36 MUm), the required time doubled. The angular maneuver
      velocity (tested between 90 and 180 degrees /s) did not have a major impact on
      the final position of the otoconia. INTERPRETATION: The two primary determinants
      for success of the SM are the time between the movements and the extension of the
      movements beyond the horizontal. The time between the movements should be at
      least 45 s. Angles of 20 degrees  or more below horizontal line (so-called
      Semont+) should increase the success rate of SM.

PMID- 27695438
TI  - Increased Bone Marrow Adiposity in a Context of Energy Deficit: The Tip of the
      Iceberg?
AB  - Elevated bone marrow adiposity (BMA) is defined as an increase in the proportion
      of the bone marrow (BM) cavity volume occupied by adipocytes. This can be caused
      by an increase in the size and/or number of adipocytes. BMA increases with age in
      a bone-site-specific manner. This increase may be linked to certain
      pathophysiological situations. Osteoporosis or compromised bone quality is
      frequently associated with high BMA. The involvement of BM adipocytes in bone
      loss may be due to commitment of mesenchymal stem cells to the adipogenic pathway
      rather than the osteogenic pathway. However, adipocytes may also act on their
      microenvironment by secreting factors with harmful effects for the bone health.
      Here, we review evidence that in a context of energy deficit (such as anorexia
      nervosa (AN) and restriction rodent models) bone alterations can occur in the
      absence of an increase in BMA. In severe cases, bone alterations are even
      associated with gelatinous BM transformation. The relationship between BMA and
      energy deficit and the potential regulators of this adiposity in this context are
      also discussed. On the basis of clinical studies and preliminary results on
      animal model, we propose that competition between differentiation into
      osteoblasts and differentiation into adipocytes might trigger bone loss at least
      in moderate-to-severe AN and in some calorie restriction models. Finally, some of
      the main questions resulting from this hypothesis are discussed.

PMID- 27695439
TI  - Encapsulation into Stealth Liposomes Enhances the Antitumor Action of Recombinant
      Cratylia mollis Lectin Expressed in Escherichia coli.
AB  - This study evaluated the in vivo antitumor potential of the recombinant lectin
      from seeds of Cratylia mollis (rCramoll) expressed in Escherichia coli, free or
      encapsulated in stealth liposomes, using mice transplanted with sarcoma 180.
      rCramoll-loaded stealth liposomes (rCramoll-lipo) were formulated by hydration of
      the lipid film followed by cycles of freezing and thawing, and about 60% of
      rCramoll was encapsulated. This novel preparation showed particle size,
      polydispersity index, and pH suitable for the evaluation of antitumor activity in
      vivo. Tumor growth inhibition rates were 59% for rCramoll and 75% for rCramoll
      lipo. Histopathological analysis of the experimental groups showed that both free
      and encapsulated lectin caused no changes in the kidneys of animals.
      Hematological analysis revealed that treatment with rCramoll-lipo significantly
      increased leukocyte concentration when compared with the untreated and rCramoll
      group. In conclusion, the encapsulation of rCramoll in stealth liposomes improves
      its antitumor activity without substantial toxicity; this approach was more
      successful than the previous results reported for pCramoll loaded into
      conventional liposomes. At this point, a crucial difference between the antitumor
      action of free and encapsulated rCramoll was found along with their effects on
      immune cells. Further investigations are required to elucidate the mechanism(s)
      of the antitumor effect induced by rCramoll.

PMID- 27695440
TI  - Nanotechnology: A Valuable Strategy to Improve Bacteriocin Formulations.
AB  - Bacteriocins are proteinaceous antibacterial compounds, produced by diverse
      bacteria, which have been successfully used as: (i) food biopreservative; (ii)
      anti-biofilm agents; and (iii) additives or alternatives to the currently
      existing antibiotics, to minimize the risk of emergence of resistant strains.
      However, there are several limitations that challenge the use of bacteriocins as
      biopreservatives/antibacterial agents. One of the most promising avenues to
      overcome these limitations is the use of nanoformulations. This review highlights
      the practical difficulties with using bacteriocins to control pathogenic
      microorganisms, and provides an overview on the role of nanotechnology in
      improving the antimicrobial activity and the physicochemical properties of these
      peptides.

PMID- 27695442
TI  - Applicability of an in-House Saponin-Based Extraction Method in Bruker Biotyper
      Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry
      System for Identification of Bacterial and Fungal Species in Positively Flagged
      Blood Cultures.
AB  - We used an in-house saponin-based extraction method to evaluate the performance
      of the Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF/MS) system for the identification of bacteria and
      fungi in 405 positively flagged blood culture bottles. Results obtained from
      MALDI-TOF/MS were compared with those obtained using conventional phenotypic
      identification methods. Of the 405 positively flagged blood culture bottles, 365
      showed monomicrobal growth and were correctly identified to the species (72.1%)
      or genus (89.6%) level using the Bruker Biotyper system. The remaining 40
      positively flagged blood culture bottles showed polymicrobial growth. Of them,
      82.5% (n = 33) of the isolates were correctly identified to the species level and
      92.5% (n = 37) to the genus level using the Bruker Biotyper system. The overall
      accuracy of identification to the genus level in flagged blood cultures was 89.5%
      for Gram-positive organisms, 93.5% for Gram-negative pathogens and 71.9% for
      fungi. Confidence scores were >=1.500 for 307 (75.8%) bottles, >=1.700 for 249
      (61.5%) bottles and >=2.000 for 142 (35.1%) bottles. None of the yeast cultures
      yielded scores >=1.700. Using an identification-score cutoff of >=1.500, the
      MALDI Biotyper correctly identified 99.2% of Gram-positive bacteria, 97.6% of
      Gram-negative bacteria and 100% of yeast isolates to the genus level and 77.6% of
      Gram-positive bacteria, 87.1% of Gram-negative bacteria and 100.0% of yeast
      isolates to the species level. The overall rate of identification using our
      protocol was 89.9% (364/405) for genus level identification and 73.1% (296/405)
      for species level identification. Yeast isolates yielded the lowest confidence
      scores, which compromised the accuracy of identification. Further optimization of
      the protein extraction procedure in positive blood cultures is needed to improve
      the rate of identification.

PMID- 27695441
TI  - High Frequency of Thermodesulfovibrio spp. and Anaerolineaceae in Association
      with Methanoculleus spp. in a Long-Term Incubation of n-Alkanes-Degrading
      Methanogenic Enrichment Culture.
AB  - In the present study, the microbial community and functional gene composition of
      a long-term active alkane-degrading methanogenic culture was established after
      two successive enrichment culture transfers and incubated for a total period of
      1750 days. Molecular analysis was conducted after the second transfer (incubated
      for 750 days) for both the active alkanes-degrading methanogenic enrichment
      cultures (T2-AE) and the background control (T2-BC). A net increase of methane as
      the end product was detected in the headspace of the enrichment cultures amended
      with long-chain n-alkanes and intermediate metabolites, including octadecanoate,
      hexadecanoate, isocaprylate, butyrate, isobutyrate, propionate, acetate, and
      formate were measured in the liquid cultures. The composition of microbial
      community shifted through the successive transfers over time of incubation.
      Sequences of bacterial and archaeal 16S rRNA gene (16S rDNA) and mcrA functional
      gene indicated that bacterial sequences affiliated to Thermodesulfovibrio spp.
      and Anaerolineaceae and archaeal sequences falling within the genus
      Methanoculleus were the most frequently encountered and thus represented the
      dominant members performing the anaerobic degradation of long-chain n-alkanes and
      methanogenesis. In addition, the presence of assA functional genes encoding the
      alkylsuccinate synthase alpha subunit indicated that fumarate addition mechanism
      could be considered as a possible initial activation step of n-alkanes in the
      present study. The succession pattern of microbial communities indicates that
      Thermodesulfovibrio spp. could be a generalist participating in the metabolism of
      intermediates, while Anaerolineaceae plays a key role in the initial activation
      of long-chain n-alkane biodegradation.

PMID- 27695443
TI  - Physical Forces Shape Group Identity of Swimming Pseudomonas putida Cells.
AB  - The often striking macroscopic patterns developed by motile bacterial populations
      on agar plates are a consequence of the environmental conditions where the cells
      grow and spread. Parameters such as medium stiffness and nutrient concentration
      have been reported to alter cell swimming behavior, while mutual interactions
      among populations shape collective patterns. One commonly observed occurrence is
      the mutual inhibition of clonal bacteria when moving toward each other, which
      results in a distinct halt at a finite distance on the agar matrix before having
      direct contact. The dynamics behind this phenomenon (i.e., intolerance to mix in
      time and space with otherwise identical others) has been traditionally explained
      in terms of cell-to-cell competition/cooperation regarding nutrient availability.
      In this work, the same scenario has been revisited from an alternative
      perspective: the effect of the physical mechanics that frame the process, in
      particular the consequences of collisions between moving bacteria and the semi
      solid matrix of the swimming medium. To this end, we set up a simple experimental
      system in which the swimming patterns of Pseudomonas putida were tested with
      different geometries and agar concentrations. A computational analysis framework
      that highlights cell-to-medium interactions was developed to fit experimental
      observations. Simulated outputs suggested that the medium is compressed in the
      direction of the bacterial front motion. This phenomenon generates what was
      termed a compression wave that goes through the medium preceding the swimming
      population and that determines the visible high-level pattern. Taken together,
      the data suggested that the mechanical effects of the bacteria moving through the
      medium created a factual barrier that impedes to merge with neighboring cells
      swimming from a different site. The resulting divide between otherwise clonal
      bacteria is thus brought about by physical forces-not genetic or metabolic
      programs.

PMID- 27695444
TI  - Riverine Bacterial Communities Reveal Environmental Disturbance Signatures within
      the Betaproteobacteria and Verrucomicrobia.
AB  - Riverine bacterial communities play an essential role in the biogeochemical
      coupling of terrestrial and marine environments, transforming elements and
      organic matter in their journey from land to sea. However, precisely due to the
      fact that rivers receive significant terrestrial input, the distinction between
      resident freshwater taxa vs. land-derived microbes can often become ambiguous.
      Furthermore, ecosystem perturbations could introduce allochthonous microbial
      groups and reshape riverine bacterial communities. Using full- and partial-length
      16S ribosomal RNA gene sequences, we analyzed the composition of bacterial
      communities in the Tar River of North Carolina from November 2010 to November
      2011, during which a natural perturbation occurred: the inundation of the lower
      reaches of an otherwise drought-stricken river associated with Hurricane Irene,
      which passed over eastern North Carolina in late August 2011. This event provided
      the opportunity to examine the microbiological, hydrological, and geochemical
      impacts of a disturbance, defined here as the large freshwater influx into the
      Tar River, superimposed on seasonal changes or other ecosystem variability
      independent of the hurricane. Our findings demonstrate that downstream
      communities are more taxonomically diverse and temporally variable than their
      upstream counterparts. More importantly, pre- vs. post-disturbance taxonomic
      comparison of the freshwater-dominant Betaproteobacteria class and the phylum
      Verrucomicrobia reveal a disturbance signature of previously undetected taxa of
      diverse origins. We use known traits of closely-related taxa to interpret the
      ecological function of disturbance-associated bacteria, and hypothesize that
      carbon cycling was enhanced post-disturbance in the Tar River, likely due to the
      flux of organic carbon into the system associated with the large freshwater
      pulse. Our analyses demonstrate the importance of geochemical and hydrological
      alterations in structuring bacterial communities, and illustrate the response of
      temperate riverine bacteria on fine taxonomic scales to a disturbance.

PMID- 27695445
TI  - CCR4-Not Complex Subunit Not2 Plays Critical Roles in Vegetative Growth,
      Conidiation and Virulence in Watermelon Fusarium Wilt Pathogen Fusarium oxysporum
      f. sp. niveum.
AB  - CCR4-Not complex is a multifunctional regulator that plays important roles in
      multiple cellular processes in eukaryotes. In the present study, the biological
      function of FonNot2, a core subunit of the CCR4-Not complex, was explored in
      Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon wilt
      disease. FonNot2 was expressed at higher levels in conidia and germinating
      conidia and during infection in Fon-inoculated watermelon roots than in mycelia.
      Targeted disruption of FonNot2 resulted in retarded vegetative growth, reduced
      conidia production, abnormal conidial morphology, and reduced virulence on
      watermelon. Scanning electron microscopy observation of infection behaviors and
      qRT-PCR analysis of in planta fungal growth revealed that the DeltaFonNot2 mutant
      was defective in the ability to penetrate watermelon roots and showed reduced
      fungal biomass in root and stem of the inoculated plants. Phenotypic and
      biochemical analyses indicated that the DeltaFonNot2 mutant displayed
      hypersensitivity to cell wall perturbing agents (e.g., Congo Red and Calcofluor
      White) and oxidative stress (e.g., H2O2 and paraquat), decreased fusaric acid
      content, and reduced reactive oxygen species (ROS) production during spore
      germination. Our data demonstrate that FonNot2 plays critical roles in regulating
      vegetable growth, conidiogenesis and conidia morphology, and virulence on
      watermelon via modulating cell wall integrity, oxidative stress response, ROS
      production and FA biosynthesis through the regulation of transcription of genes
      involved in multiple pathways.

PMID- 27695446
TI  - Interplays between Soil-Borne Plant Viruses and RNA Silencing-Mediated Antiviral
      Defense in Roots.
AB  - Although the majority of plant viruses are transmitted by arthropod vectors and
      invade the host plants through the aerial parts, there is a considerable number
      of plant viruses that infect roots via soil-inhabiting vectors such as
      plasmodiophorids, chytrids, and nematodes. These soil-borne viruses belong to
      diverse families, and many of them cause serious diseases in major crop plants.
      Thus, roots are important organs for the life cycle of many viruses. Compared to
      shoots, roots have a distinct metabolism and particular physiological
      characteristics due to the differences in development, cell composition, gene
      expression patterns, and surrounding environmental conditions. RNA silencing is
      an important innate defense mechanism to combat virus infection in plants, but
      the specific information on the activities and molecular mechanism of RNA
      silencing-mediated viral defense in root tissue is still limited. In this review,
      we summarize and discuss the current knowledge regarding RNA silencing aspects of
      the interactions between soil-borne viruses and host plants. Overall, research
      evidence suggests that soil-borne viruses have evolved to adapt to the distinct
      mechanism of antiviral RNA silencing in roots.

PMID- 27695447
TI  - Production of the Bioactive Compounds Violacein and Indolmycin Is Conditional in
      a maeA Mutant of Pseudoalteromonas luteoviolacea S4054 Lacking the Malic Enzyme.
AB  - It has previously been reported that some strains of the marine bacterium
      Pseudoalteromonas luteoviolacea produce the purple bioactive pigment violacein as
      well as the antibiotic compound indolmycin, hitherto only found in Streptomyces.
      The purpose of the present study was to determine the relative role of each of
      these two compounds as antibacterial compounds in P. luteoviolacea S4054. Using
      Tn10 transposon mutagenesis, a mutant strain that was significantly reduced in
      violacein production in mannose-containing substrates was created. Full genome
      analyses revealed that the vio-biosynthetic gene cluster was not interrupted by
      the transposon; instead the insertion was located to the maeA gene encoding the
      malic enzyme. Supernatant of the mutant strain inhibited Vibrio anguillarum and
      Staphylococcus aureus in well diffusion assays and in MIC assays at the same
      level as the wild type strain. The mutant strain killed V. anguillarum in co
      culture experiments as efficiently as the wild type. Using UHPLC-UV/Vis analyses,
      we quantified violacein and indolmycin, and the mutant strain only produced 7-10%
      the amount of violacein compared to the wild type strain. In contrast, the amount
      of indolmycin produced by the mutant strain was about 300% that of the wild type.
      Since inhibition of V. anguillarum and S. aureus by the mutant strain was similar
      to that of the wild type, it is concluded that violacein is not the major
      antibacterial compound in P. luteoviolacea. We furthermore propose that
      production of violacein and indolmycin may be metabolically linked and that yet
      unidentified antibacterial compound(s) may be play a role in the antibacterial
      activity of P. luteoviolacea.

PMID- 27695448
TI  - Proteomics Analysis Revealed that Crosstalk between Helicobacter pylori and
      Streptococcus mitis May Enhance Bacterial Survival and Reduces Carcinogenesis.
AB  - Helicobacter pylori is the dominant species of the human gastric microbiota and
      is present in the stomach of more than half of the human population worldwide.
      Colonization by H. pylori causes persistent inflammatory response and H. pylori
      induced gastritis is the strongest singular risk factor for the development of
      gastric adenocarcinoma. However, only a small proportion of infected individuals
      develop malignancy. Besides H. pylori, other microbial species have also been
      shown to be related to gastritis. We previously reported that interspecies
      microbial interaction between H. pylori and S. mitis resulted in alteration of
      their metabolite profiles. In this study, we followed up by analyzing the
      changing protein profiles of H. pylori and S. mitis by LC/Q-TOF mass spectrometry
      to understand the different response of the two bacterial species in a multi
      species micro-environment. Differentially-expressed proteins in mono- and co
      cultures could be mapped into 18 biological pathways. The number of proteins
      involve in RNA degradation, nucleotide excision repair, mismatch repair, and
      lipopolysaccharide (LPS) biosynthesis were increased in co-cultured H. pylori. On
      the other hand, fewer proteins involve in citrate cycle, glycolysis/
      gluconeogenesis, aminoacyl-tRNA biosynthesis, translation, metabolism, and cell
      signaling were detected in co-cultured H. pylori. This is consistent with our
      previous observation that in the presence of S. mitis, H. pylori was transformed
      to coccoid. Interestingly, phosphoglycerate kinase (PGK), a major enzyme used in
      glycolysis, was found in abundance in co-cultured S. mitis and this may have
      enhanced the survival of S. mitis in the multi-species microenvironment. On the
      other hand, thioredoxin (TrxA) and other redox-regulating enzymes of H. pylori
      were less abundant in co-culture possibly suggesting reduced oxidative stress.
      Oxidative stress plays an important role in tissue damage and carcinogenesis.
      Using the in vitro co-culture model, this study emphasized the possibility that
      pathogen-microbiota interaction may have a protective effect against H. pylori
      associated carcinogenesis.

PMID- 27695450
TI  - Genetic and Phenotypic Characterization of a Salmonella enterica serovar
      Enteritidis Emerging Strain with Superior Intra-macrophage Replication Phenotype.
AB  - Salmonella enterica serovar Enteritidis (S. Enteritidis) is one of the ubiquitous
      Salmonella serovars worldwide and a major cause of food-born outbreaks, which are
      often associated with poultry and poultry derivatives. Here we report a nation
      wide S. Enteritidis clonal outbreak that occurred in Israel during the last third
      of 2015. Pulsed field gel electrophoresis and whole genome sequencing identified
      genetically related strains that were circulating in Israel as early as 2008.
      Global comparison linked this outbreak strain to several clinical and marine
      environmental isolates that were previously isolated in California and Canada,
      indicating that similar strains are prevalent outside of Israel. Phenotypic
      comparison between the 2015 outbreak strain and other clinical and reference S.
      Enteritidis strains showed only limited intra-serovar phenotypic variation in
      growth in rich medium, invasion into Caco-2 cells, uptake by J774.1A macrophages,
      and host cell cytotoxicity. In contrast, significant phenotypic variation was
      shown among different S. Enteritidis isolates when biofilm-formation, motility,
      invasion into HeLa cells and uptake by THP-1 human macrophages were studied.
      Interestingly, the 2015 outbreak clone was found to possess superior intra
      macrophage replication ability within both murine and human macrophages in
      comparison to the other S. Enteritidis strains studied. This phenotype is likely
      to play a role in the virulence and host-pathogen interactions of this emerging
      clone.

PMID- 27695452
TI  - Draft Genome Sequence of Mangrove-Derived Streptomyces sp. MUSC 125 with
      Antioxidant Potential.

PMID- 27695449
TI  - Pyrethroid-Degrading Microorganisms and Their Potential for the Bioremediation of
      Contaminated Soils: A Review.
AB  - Pyrethroid insecticides have been used to control pests in agriculture, forestry,
      horticulture, public health and for indoor home use for more than 20 years.
      Because pyrethroids were considered to be a safer alternative to organophosphate
      pesticides (OPs), their applications significantly increased when the use of OPs
      was banned or limited. Although, pyrethroids have agricultural benefits, their
      widespread and continuous use is a major problem as they pollute the terrestrial
      and aquatic environments and affect non-target organisms. Since pyrethroids are
      not degraded immediately after application and because their residues are
      detected in soils, there is an urgent need to remediate pyrethroid-polluted
      environments. Various remediation technologies have been developed for this
      purpose; however, bioremediation, which involves bioaugmentation and/or
      biostimulation and is a cost-effective and eco-friendly approach, has emerged as
      the most advantageous method for cleaning-up pesticide-contaminated soils. This
      review presents an overview of the microorganisms that have been isolated from
      pyrethroid-polluted sites, characterized and applied for the degradation of
      pyrethroids in liquid and soil media. The paper is focused on the microbial
      degradation of the pyrethroids that have been most commonly used for many years
      such as allethrin, bifenthrin, cyfluthrin, cyhalothrin, cypermethrin,
      deltamethrin, fenpropathrin, fenvalerate, and permethrin. Special attention is
      given to the bacterial strains from the genera Achromobacter, Acidomonas,
      Bacillus, Brevibacterium, Catellibacterium, Clostridium, Lysinibacillus,
      Micrococcus, Ochrobactrum, Pseudomonas, Serratia, Sphingobium, Streptomyces, and
      the fungal strains from the genera Aspergillus, Candida, Cladosporium, and
      Trichoderma, which are characterized by their ability to degrade various
      pyrethroids. Moreover, the current knowledge on the degradation pathways of
      pyrethroids, the enzymes that are involved in the cleavage of pesticide
      molecules, the factors/conditions that influence the survival of strains that are
      introduced into soil and the rate of the removal of pyrethroids are also
      discussed. This knowledge may be useful to optimize the environmental conditions
      of bioremediation and may be crucial for the effective removal of pyrethroids
      from polluted soils.

PMID- 27695451
TI  - Persistence and Potential Viable but Non-culturable State of Pathogenic Bacteria
      during Storage of Digestates from Agricultural Biogas Plants.
AB  - Despite the development of on-farm anaerobic digestion as a process for making
      profitable use of animal by-products, factors leading to the inactivation of
      pathogenic bacteria during storage of digestates remain poorly described. Here, a
      microcosm approach was used to evaluate the persistence of three pathogenic
      bacteria (Salmonella enterica Derby, Campylobacter coli and Listeria
      monocytogenes) in digestates from farms, stored for later land spreading. Nine
      samples, including raw digestates, liquid fractions of digestate and composted
      digestates, were inoculated with each pathogen and maintained for 40 days at 24
      degrees C. Concentrations of pathogens were monitored using culture and qPCR
      methods. The persistence of L. monocytogenes, detected up to 20 days after
      inoculation, was higher than that of Salmonella Derby, detected for 7-20 days,
      and of C. coli (not detected after 7 days). In some digestates, the concentration
      of the pathogens by qPCR assay was several orders of magnitude higher than the
      concentration of culturable cells, suggesting a potential loss of culturability
      and induction of Viable but Non-Culturable (VBNC) state. The potential VBNC state
      which was generally not observed in the same digestate for the three pathogens,
      occurred more frequently for C. coli and L. monocytogenes than for Salmonella
      Derby. Composting a digestate reduced the persistence of seeded L. monocytogenes
      but promoted the maintenance of Salmonella Derby. The effect of NH[Formula: see
      text]/NH3 on the culturability of C. coli and Salmonella Derby was also shown.
      The loss of culturability may be the underlying mechanism for the regrowth of
      pathogens. We have also demonstrated the importance of using molecular tools to
      monitor pathogens in environmental samples since culture methods may
      underestimate cell concentration. Our results underline the importance of
      considering VBNC cells when evaluating the sanitary effect of an anaerobic
      digestion process and the persistence of pathogens during the storage of
      digestates and subsequent land spreading.

PMID- 27695453
TI  - CMV-Specific CD8 T Cell Differentiation and Localization: Implications for
      Adoptive Therapies.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection
      and, thus, is one of the most common infectious complications of immune
      suppression. Adoptive transfer of HCMV-specific T cells has emerged as an
      effective method to reduce the risk for HCMV infection and/or reactivation by
      restoring immunity in transplant recipients. However, the CMV-specific CD8+ T
      cell response is comprised of a heterogenous mixture of subsets with distinct
      functions and localization, and it is not clear if current adoptive immunotherapy
      protocols can reconstitute the full spectrum of CD8+ T cell immunity. The aim of
      this review is to briefly summarize the role of these T cell subsets in CMV
      immunity and to describe how current adoptive immunotherapy practices might
      affect their reconstitution in patients. The bulk of the CMV-specific CD8+ T cell
      population is made up of terminally differentiated effector T cells with
      immediate effector function and a short life span. Self-renewing memory T cells
      within the CMV-specific population retain the capacity to expand and
      differentiate upon challenge and are important for the long-term persistence of
      the CD8+ T cell response. Finally, mucosal organs, which are frequent sites of
      CMV reactivation, are primarily inhabited by tissue-resident memory T cells,
      which do not recirculate. Future work on adoptive transfer strategies may need to
      focus on striking a balance between the formation of these subsets to ensure the
      development of long lasting and protective immune responses that can access the
      organs affected by CMV disease.

PMID- 27695454
TI  - Induction of Hematopoietic Microchimerism by Gene-Modified BMT Elicits Antigen
      Specific B and T Cell Unresponsiveness toward Gene Therapy Products.
AB  - BACKGROUND: Gene therapy is a promising treatment option for hemophilia and other
      protein deficiencies. However, immune responses against the transgene product
      represent an obstacle to safe and effective gene therapy, urging for the
      implementation of tolerization strategies. Induction of a hematopoietic chimerism
      via bone marrow transplantation (BMT) is a potent means for inducing
      immunological tolerance in solid organ transplantation. OBJECTIVES: We reasoned,
      here, that the same viral vector could be used, first, to transduce BM cells for
      inducing chimerism-associated transgene-specific immune tolerance and, second,
      for correcting protein deficiencies by vector-mediated systemic production of the
      deficient coagulation factor. METHODS: Evaluation of strategies to induce B and T
      cell tolerance was performed using ex vivo gene transfer with lentiviral (LV)
      vectors encoding coagulation factor IX (FIX) or the SIINFEKL epitope of
      ovalbumin. Following induction of microchimerism via BMT, animals were challenged
      with in vivo gene transfer with LV vectors. RESULTS: The experimental approach
      prevented humoral immune response against FIX, resulting in persistence of
      therapeutic levels of circulating FIX, after LV-mediated gene transfer in vivo.
      In an ovalbumin model, we also demonstrated that this approach effectively
      tolerized the CD8+ T cell compartment in an antigen-specific manner. CONCLUSION:
      These results provide the proof-of-concept that inducing a microchimerism by gene
      modified BMT is a powerful tool to provide transgene-specific B and T cell
      tolerance in a gene therapy setting.

PMID- 27695455
TI  - Tissue-Specific Expression Patterns of MicroRNA during Acute Graft-versus-Host
      Disease in the Rat.
AB  - MicroRNAs (miRNA) have emerged as central regulators of diverse biological
      processes and contribute to driving pathology in several diseases. Acute graft
      versus-host disease (aGvHD) represents a major complication after allogeneic
      hematopoietic stem cell transplantation, caused by alloreactive donor T cells
      attacking host tissues leading to inflammation and tissue destruction. Changes in
      miRNA expression patterns occur during aGvHD, and we hypothesized that we could
      identify miRNA signatures in target tissues of aGvHD that may potentially help
      understand the underlying molecular pathology of the disease. We utilized a rat
      model of aGvHD with transplantation of fully MHC-mismatched T cell depleted bone
      marrow, followed by infusion of donor T cells. The expression pattern of 423 rat
      miRNAs was investigated in skin, gut, and lung tissues and intestinal T cells
      with the NanoString hybridization platform, in combination with validation by
      quantitative PCR. MHC-matched transplanted rats were included as controls. In the
      skin, upregulation of miR-34b and downregulation of miR-326 was observed, while
      in the intestines, we detected downregulation of miR-743b and a trend toward
      downregulation of miR-345-5p. Thus, tissue-specific expression patterns of miRNAs
      were observed. Neither miR-326 nor miR-743b has previously been associated with
      aGvHD. Moreover, we identified upregulation of miR-146a and miR-155 in skin
      tissue of rats suffering from aGvHD. Analysis of intestinal T cells indicated 23
      miRNAs differentially regulated between aGvHD and controls. Two of these miRNAs
      were differentially expressed either in skin (miR-326) or in intestinal (miR-345
      5p) tissue. Comparison of intestinal and peripheral blood T cells indicated
      common dysregulated expression of miR-99a, miR-223, miR-326, and miR-345-5p.
      Analysis of predicted gene targets for these miRNAs indicated potential targeting
      of an inflammatory network both in skin and in the intestines that may further
      regulate inflammatory cytokine production. In conclusion, comprehensive miRNA
      profiling in rats suffering from aGvHD demonstrate tissue-specific differences in
      the expression patterns of miRNA that may not be detected by profiling of
      peripheral blood T cells alone. These tissue-specific miRNAs may contribute to
      distinct pathologic mechanisms and could represent potential targets for therapy.

PMID- 27695456
TI  - Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem
      Cell Transplantation.
AB  - Bone marrow failure (BMF) syndromes are severe complications of allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). In this paper, we
      distinguish two different entities, the graft failure (GF) and the poor graft
      function (PGF), and we review the current understanding of the interactions
      between the immune and hematopoietic compartments in these conditions. We first
      discuss how GF occurs as the result of classical alloreactive immune responses
      mediated by residual host cellular and humoral immunity persisting after
      conditioning and prevented by host and donor regulatory T cells. We next
      summarize the current knowledge about the contribution of inflammatory mediators
      to the development of PGF. In situations of chronic inflammation complicating
      allo-HSCT, such as graft-versus-host disease or infections, PGF seems to be
      essentially the result of a sustained impairment of hematopoietic stem cells
      (HSC) self-renewal and proliferation caused by inflammatory mediators, such as
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha, and of induction of
      apoptosis through the Fas/Fas ligand pathway. Interestingly, the production of
      inflammatory molecules leads to a non-MHC restricted, bystander inhibition of
      hematopoiesis, therefore, representing a promising target for immunological
      interventions. Finally, we discuss immune-mediated impairment of bone marrow
      microenvironment as a potential mechanism hampering hematopoietic recovery.
      Better understanding of immunological mechanisms responsible for BMF syndromes
      after allo-HSCT may lead to the development of more efficient immunotherapeutic
      interventions.

PMID- 27695458
TI  - Tomato phyE Is Required for Shade Avoidance in the Absence of phyB1 and phyB2.
AB  - The phytochrome (phy) family of red and far-red photoreceptors provides plants
      with critical information about their surrounding environment and can signal
      downstream developmental and physiological changes. Neighboring plants compete
      for limited light resources, and their presence is detected by the phytochrome
      photoreceptors as a reduced ratio of red: far-red light. One common response to
      shade is increased elongation of petioles and internodes to compete with their
      neighbors. While the phytochrome family, phyB in particular, has been well
      studied in Arabidopsis, information about the other phytochrome family members is
      limited, especially in sympodial crop plants such as tomato, that have a very
      different architecture from that of the model plant. To study the tomato
      phytochrome family we took advantage of several existing mutants and generated an
      artificial miRNA (amiRNA) line to target SlPHYE, the remaining phytochrome B
      subfamily member with no currently available mutant line. Here, we characterize
      internode elongation and shade avoidance phenotypes of the SlPHYE amiRNA line
      (PHYE amiRNA). In addition, higher order phytochrome subfamily B mutants were
      generated with the PHYE amiRNA line to investigate the role of SlphyE within the
      phyB subfamily. We find that the PHYE amiRNA line has no detectable phenotype on
      its own, however in higher order combinations with SlphyB1 and/or SlphyB2 there
      are notable defects in shade avoidance. Most notably, we find that the triple
      mutant combination of SlPHYE amiRNA, SlphyB1, and SlphyB2 has a phenotype that is
      much stronger than the SlphyB1 SlphyB2 double, showing constitutive shade
      avoidance and little to no response to shade. This indicates that SlphyE is
      required for the shade avoidance response in the absence of SlphyB1 and SlphyB2.

PMID- 27695457
TI  - Impact of Viral Infections on Hematopoiesis: From Beneficial to Detrimental
      Effects on Bone Marrow Output.
AB  - The ability of the bone marrow (BM) to generate copious amounts of blood cells
      required on a daily basis depends on a highly orchestrated process of
      proliferation and differentiation of hematopoietic stem and progenitor cells
      (HSPCs). This process can be rapidly adapted under stress conditions, such as
      infections, to meet the specific cellular needs of the immune response and the
      ensuing physiological changes. This requires a tight regulation in order to
      prevent either hematopoietic failure or transformation. Although adaptation to
      bacterial infections or systemic inflammation has been studied and reviewed in
      depth, specific alterations of hematopoiesis to viral infections have received
      less attention so far. Viruses constantly pose a significant health risk and
      demand an adequate, balanced response from our immune system, which also affects
      the BM. In fact, both the virus itself and the ensuing immune response can have a
      tremendous impact on the hematopoietic process. On one hand, this can be
      beneficial: it helps to boost the cellular response of the body to resolve the
      viral infection. But on the other hand, when the virus and the resulting
      antiviral response persist, the inflammatory feedback to the hematopoietic system
      will become chronic, which can be detrimental for a balanced BM output. Chronic
      viral infections frequently have clinical manifestations at the level of blood
      cell formation, and we summarize which viruses can lead to BM pathologies, like
      aplastic anemia, pancytopenia, hemophagocytic lymphohistiocytosis,
      lymphoproliferative disorders, and malignancies. Regarding the underlying
      mechanisms, we address specific effects of acute and chronic viral infections on
      blood cell production. As such, we distinguish four different levels in which
      this can occur: (1) direct viral infection of HSPCs, (2) viral recognition by
      HSPCs, (3) indirect effects on HSPCs by inflammatory mediators, and (4) the role
      of the BM microenvironment on hematopoiesis upon virus infection. In conclusion,
      this review provides a comprehensive overview on how viral infections can affect
      the formation of new blood cells, aiming to advance our understanding of the
      underlying cellular and molecular mechanisms to improve the treatment of BM
      failure in patients.

PMID- 27695459
TI  - OsPEX11, a Peroxisomal Biogenesis Factor 11, Contributes to Salt Stress Tolerance
      in Oryza sativa.
AB  - Peroxisomes are single membrane-bound organelles, whose basic enzymatic
      constituents are catalase and H2O2-producing flavin oxidases. Previous reports
      showed that peroxisome is involved in numerous processes including primary and
      secondary metabolism, plant development and abiotic stress responses. However,
      knowledge on the function of different peroxisome genes from rice and its
      regulatory roles in salt and other abiotic stresses is limited. Here, a novel
      prey protein, OsPEX11 (Os03g0302000), was screened and identified by yeast two
      hybrid and GST pull-down assays. Phenotypic analysis of OsPEX11 overexpression
      seedlings demonstrated that they had better tolerance to salt stress than wild
      type (WT) and OsPEX11-RNAi seedlings. Compared with WT and OsPEX11-RNAi
      seedlings, overexpression of OsPEX11 had lower level of lipid peroxidation,
      Na+/K+ ratio, higher activities of antioxidant enzymes (SOD, POD, and CAT) and
      proline accumulation. Furthermore, qPCR data suggested that OsPEX11 acted as a
      positive regulator of salt tolerance by reinforcing the expression of several
      well-known rice transporters (OsHKT2;1, OsHKT1;5, OsLti6a, OsLti6b, OsSOS1,
      OsNHX1, and OsAKT1) involved in Na+/K+ homeostasis in transgenic plants under
      salinity. Ultrastructural observations of OsPEX11-RNAi seedlings showed that they
      were less sensitive to salt stress than WT and overexpression lines. These
      results provide experimental evidence that OsPEX11 is an important gene
      implicated in Na+ and K+ regulation, and plays a critical role in salt stress
      tolerance by modulating the expression of cation transporters and antioxidant
      defense. Thus, OsPEX11 could be considered in transgenic breeding for improvement
      of salt stress tolerance in rice crop.

PMID- 27695460
TI  - EjODO1, a MYB Transcription Factor, Regulating Lignin Biosynthesis in Developing
      Loquat (Eriobotrya japonica) Fruit.
AB  - Lignin is important for plant secondary cell wall formation and participates in
      resistance to various biotic and abiotic stresses. Loquat undergoes lignification
      not only in vegetative tissues but also in flesh of postharvest fruit, which
      adversely affects consumer acceptance. Thus, researches on lignin biosynthesis
      and regulation are important to understand loquat fruit lignification. In loquat,
      a gene encoding an enzyme in the lignin biosynthesis pathway, Ej4CL1, was
      reported to be regulated by transcription factors, including EjMYB1, EjMYB2,
      EjMYB8, and EjAP2-1, knowledge of this process is still limited. With the aim of
      identifying novel transcriptional factors controlling lignin biosynthesis in
      loquat, the promoter of Ej4CL1 was utilized to screen a cDNA library by yeast one
      hybrid assay. A novel R2R3 MYB, named EjODO1, was identified. Real-time PCR
      analyses indicated that EjODO1 is highly expressed in lignified stems and roots.
      During fruit development, expression of EjODO1 decreased along with the reduction
      of lignin content and became undetectable in mature ripe fruit. Thus, EjODO1 is
      likely to be involved in lignification of vegetative organs and early fruit
      development but not in mature fruit or postharvest lignification. Dual-luciferase
      assay indicated that EjODO1 could trans-activate promoters of lignin biosynthesis
      genes, such as EjPAL1, Ej4CL1, and Ej4CL5 and transient overexpression of EjODO1
      triggered lignin biosynthesis. These results indicate a role for EjODO1 in
      regulating lignin biosynthesis in loquat which is different from the previously
      characterized transcription factors.

PMID- 27695461
TI  - A High-Resolution InDel (Insertion-Deletion) Markers-Anchored Consensus Genetic
      Map Identifies Major QTLs Governing Pod Number and Seed Yield in Chickpea.
AB  - Development and large-scale genotyping of user-friendly informative genome/gene
      derived InDel markers in natural and mapping populations is vital for
      accelerating genomics-assisted breeding applications of chickpea with minimal
      resource expenses. The present investigation employed a high-throughput whole
      genome next-generation resequencing strategy in low and high pod number parental
      accessions and homozygous individuals constituting the bulks from each of two
      inter-specific mapping populations [(Pusa 1103 * ILWC 46) and (Pusa 256 * ILWC
      46)] to develop non-erroneous InDel markers at a genome-wide scale. Comparing
      these high-quality genomic sequences, 82,360 InDel markers with reference to
      kabuli genome and 13,891 InDel markers exhibiting differentiation between low and
      high pod number parental accessions and bulks of aforementioned mapping
      populations were developed. These informative markers were structurally and
      functionally annotated in diverse coding and non-coding sequence components of
      genome/genes of kabuli chickpea. The functional significance of regulatory and
      coding (frameshift and large-effect mutations) InDel markers for establishing
      marker-trait linkages through association/genetic mapping was apparent. The
      markers detected a greater amplification (97%) and intra-specific polymorphic
      potential (58-87%) among a diverse panel of cultivated desi, kabuli, and wild
      accessions even by using a simpler cost-efficient agarose gel-based assay
      implicating their utility in large-scale genetic analysis especially in
      domesticated chickpea with narrow genetic base. Two high-density inter-specific
      genetic linkage maps generated using aforesaid mapping populations were
      integrated to construct a consensus 1479 InDel markers-anchored high-resolution
      (inter-marker distance: 0.66 cM) genetic map for efficient molecular mapping of
      major QTLs governing pod number and seed yield per plant in chickpea. Utilizing
      these high-density genetic maps as anchors, three major genomic regions harboring
      each of pod number and seed yield robust QTLs (15-28% phenotypic variation
      explained) were identified on chromosomes 2, 4, and 6. The integration of genetic
      and physical maps at these QTLs mapped on chromosomes scaled-down the long major
      QTL intervals into high-resolution short pod number and seed yield robust QTL
      physical intervals (0.89-2.94 Mb) which were essentially got validated in
      multiple genetic backgrounds of two chickpea mapping populations. The genome-wide
      InDel markers including natural allelic variants and genomic loci/genes
      delineated at major six especially in one colocalized novel congruent robust pod
      number and seed yield robust QTLs mapped on a high-density consensus genetic map
      were found most promising in chickpea. These functionally relevant molecular tags
      can drive marker-assisted genetic enhancement to develop high-yielding cultivars
      with increased seed/pod number and yield in chickpea.

PMID- 27695462
TI  - Impact of Wheat/Faba Bean Mixed Cropping or Rotation Systems on Soil Microbial
      Functionalities.
AB  - Cropping systems based on carefully designed species mixtures reveal many
      potential advantages in terms of enhancing crop productivity, reducing pest and
      diseases, and enhancing ecological services. Associating cereals and legume
      production either through intercropping or rotations might be a relevant strategy
      of producing both type of culture, while benefiting from combined nitrogen fixed
      by the legume through its symbiotic association with nitrogen-fixing bacteria,
      and from a better use of P and water through mycorrhizal associations. These
      practices also participate to the diversification of agricultural productions,
      enabling to secure the regularity of income returns across the seasonal and
      climatic uncertainties. In this context, we designed a field experiment aiming to
      estimate the 2 years impact of these practices on wheat yield and on soil
      microbial activities as estimated through Substrate Induced Respiration method
      and mycorrhizal soil infectivity (MSI) measurement. It is expected that
      understanding soil microbial functionalities in response to these agricultural
      practices might allows to target the best type of combination, in regard to crop
      productivity. We found that the tested cropping systems largely impacted soil
      microbial functionalities and MSI. Intercropping gave better results in terms of
      crop productivity than the rotation practice after two cropping seasons. Benefits
      resulting from intercrop should be highly linked with changes recorded on soil
      microbial functionalities.

PMID- 27695463
TI  - Variation in Host and Pathogen in the Neonectria/Malus Interaction; toward an
      Understanding of the Genetic Basis of Resistance to European Canker.
AB  - Apple canker caused by the phytopathogenic fungus Neonectria ditissima is an
      economically important disease, which has spread in recent years to almost all
      pome-producing regions of the world. N. ditissima is able to cross-infect a wide
      range of apple varieties and causes branch and trunk lesions, known as cankers.
      Most modern apple varieties are susceptible and in extreme cases suffer from high
      mortality (up to 50%) in the early phase of orchard establishment. There is no
      known race structure of the pathogen and the global level of genetic diversity of
      the pathogen population is unknown. Resistance breeding is underway in many
      global breeding programmes, but nevertheless, a total resistance to canker has
      not yet been demonstrated. Here we present preliminary data from a survey of the
      phylogenetic relationships between global isolates of N. ditissima which reveals
      only slight evidence for population structure. In addition we report the results
      of four rapid screening tests to assess the response to N. ditissima in different
      apple scion and rootstock varieties, which reveals abundant variation in
      resistance responses in both cultivar and rootstock material. Further seedling
      tests show that the segregation patterns of resistance and susceptibility vary
      widely between crosses. We discuss inconsistencies in test performance with field
      observations and discuss future research opportunities in this area.

PMID- 27695464
TI  - Co-ordination in Morphological Leaf Traits of Early Diverging Angiosperms Is
      Maintained Following Exposure to Experimental Palaeo-atmospheric Conditions of
      Sub-ambient O2 and Elevated CO2.
AB  - In order to be successful in a given environment a plant should invest in a vein
      network and stomatal distribution that ensures balance between both water supply
      and demand. Vein density (Dv) and stomatal density (SD) have been shown to be
      strongly positively correlated in response to a range of environmental variables
      in more recently evolved plant species, but the extent of this relationship has
      not been confirmed in earlier diverging plant lineages. In order to examine the
      effect of a changing atmosphere on the relationship between Dv and SD, five early
      diverging plant species representing two different reproductive plant grades were
      grown for 7 months in a palaeo-treatment comprising an O2:CO2 ratio that has
      occurred multiple times throughout plant evolutionary history. Results show a
      range of species-specific Dv and SD responses to the palaeo-treatment, however,
      we show that the strong relationship between Dv and SD under modern ambient
      atmospheric composition is maintained following exposure to the palaeo-treatment.
      This suggests strong inter-specific co-ordination between vein and stomatal
      traits for our study species even under relatively extreme environmental change.
      This co-ordination supports existing plant function proxies that use the distance
      between vein endings and stomata (Dm) to infer plant palaeo-physiology.

PMID- 27695465
TI  - Transcriptome Profiling of Petal Abscission Zone and Functional Analysis of an
      Aux/IAA Family Gene RhIAA16 Involved in Petal Shedding in Rose.
AB  - Roses are one of the most important cut flowers among ornamental plants. Rose
      flower longevity is largely dependent on the timing of petal shedding occurrence.
      To understand the molecular mechanism underlying petal abscission in rose, we
      performed transcriptome profiling of the petal abscission zone during petal
      shedding using Illumina technology. We identified a total of 2592 differentially
      transcribed genes (DTGs) during rose petal shedding. Gene ontology term
      enrichment and pathway analysis revealed that major biochemical pathways the DTGs
      were involved in included ethylene biosynthesis, starch degradation, superpathway
      of cytosolic glycolysis, pyruvate dehydrogenase and TCA cycle, photorespiration
      and the lactose degradation III pathway. This suggests that alterations in carbon
      metabolism are an important part of rose petal abscission. Among these DTGs,
      approximately 150 genes putatively encoding transcription factors were identified
      in rose abscission zone. These included zinc finger, WRKY, ERF, and Aux/IAA gene
      families, suggesting that petal abscission involves complex transcriptional
      reprogramming. Approximately 108 DTGs were related to hormone pathways, of which
      auxin and ethylene related DTGs were the largest groups including 52 and 41
      genes, respectively. These also included 12 DTGs related to gibberellin and 6
      DTGs in jasmonic acid pathway. Surprisingly, no DTGs involved in the
      biosynthesis/signaling of abscisic acid, cytokinin, brassinosteroid, and
      salicylic acid pathways were detected. Moreover, among DTGs related to auxin, we
      identified an Aux/IAA gene RhIAA16 that was up-regulated in response to petal
      shedding. Down-regulation of RhIAA16 by virus-induced gene silencing in rose
      promoted petal abscission, suggesting that RhIAA16 plays an important role in
      rose petal abscission.

PMID- 27695466
TI  - Expression of the Grape VqSTS21 Gene in Arabidopsis Confers Resistance to Osmotic
      Stress and Biotrophic Pathogens but Not Botrytis cinerea.
AB  - Stilbene synthase (STS) is a key gene in the biosynthesis of various stilbenoids,
      including resveratrol and its derivative glucosides (such as piceid), that has
      been shown to contribute to disease resistance in plants. However, the mechanism
      behind such a role has yet to be elucidated. Furthermore, the function of STS
      genes in osmotic stress tolerance remains unclear. As such, we sought to
      elucidate the role of STS genes in the defense against biotic and abiotic stress
      in the model plant Arabidopsis thaliana. Expression profiling of 31 VqSTS genes
      from Vitis quinquangularis revealed that VqSTS21 was up-regulated in response to
      powdery mildew (PM) infection. To provide a deeper understanding of the function
      of this gene, we cloned the full-length coding sequence of VqSTS21 and
      overexpressed it in Arabidopsis thaliana via Agrobacterium-mediated
      transformation. The resulting VqSTS21 Arabidopsis lines produced trans-piceid
      rather than resveratrol as their main stilbenoid product and exhibited improved
      disease resistance to PM and Pseudomonas syringae pv. tomato DC3000, but
      displayed increased susceptibility to Botrytis cinerea. In addition, transgenic
      Arabidopsis lines were found to confer tolerance to salt and drought stress from
      seed germination through plant maturity. Intriguingly, qPCR assays of defense
      related genes involved in salicylic acid, jasmonic acid, and abscisic acid
      induced signaling pathways in these transgenic lines suggested that VqSTS21 plays
      a role in various phytohormone-related pathways, providing insight into the
      mechanism behind VqSTS21-mediated resistance to biotic and abiotic stress.

PMID- 27695467
TI  - Sulfur Mediated Alleviation of Mn Toxicity in Polish Wheat Relates to Regulating
      Mn Allocation and Improving Antioxidant System.
AB  - Sulfur (S) is an essential macronutrient that has been proved to play an
      important role in regulating plant responses to various biotic and abiotic
      stresses. The present study was designed to investigate the effect of S status on
      polish wheat plant response to Mn toxicity. Results showed that Mn stress
      inhibited plant growth, disturbed photosynthesis and induced oxidative stress. In
      response to Mn stress, polish wheat plant activated several detoxification
      mechanisms to counteract Mn toxicity, including enhanced antioxidant defense
      system, increased Mn distribution in the cell wall and up-regulated genes
      involved in S assimilation. Moderate S application was found to alleviate Mn
      toxicity mainly by sequestering excess Mn into vacuoles, inhibiting Mn
      translocation from roots to shoots, stimulating activities of antioxidant enzymes
      and enhancing GSH production via up-regulating genes involved in S metabolism.
      However, application of high level S to Mn-stressed plants did not significantly
      alleviated Mn toxicity likely due to osmotic stress. In conclusion, moderate S
      application is beneficial to polish wheat plant against Mn toxicity, S exerts its
      effects via stimulating the antioxidant defense system and regulating the
      translocation and subcellular distribution of Mn, in which processes GSH plays an
      indispensable role.

PMID- 27695470
TI  - Aploneura lentisci (Homoptera: Aphididae) and Its Interactions with Fungal
      Endophytes in Perennial Ryegrass (Lolium perenne).
AB  - Aploneura lentisci Pass. is endemic to the Mediterranean region where it is
      holocyclic, forming galls on its primary host, Pistacia lentiscus and alternating
      over a 2-year period between Pistacia and secondary hosts, principally species of
      Gramineae. This aphid is widely distributed in Australia and New Zealand on the
      roots of the common forage grasses, ryegrass (Lolium spp.) and tall fescue
      (Schedonorus phoenix) where it exists as permanent, anholocyclic, parthenogenetic
      populations. Previous studies have indicated that infestations of A. lentisci
      significantly reduce plant growth and may account for differences in field
      performance of Lolium perenne infected with different strains of the fungal
      endophyte Epichloe festucae var. lolii. These obligate biotrophs protect their
      host grasses from herbivory via the production of alkaloids. To confirm the
      hypothesis that growth of L. perenne is associated with the effect of different
      endophyte strains on aphid populations, herbage and root growth were measured
      over time in two pot trials that compared three fungal endophyte strains with an
      endophyte-free control. In both pot trials, aphid numbers were lowest on plants
      infected with endophyte strain AR37 at all sampling times. In plants infected
      with a common toxic strain naturalized in New Zealand, aphid numbers overall were
      lower than on uninfected plants or those infected with strain AR1, but numbers
      did not always differ significantly from these treatments. Populations on AR1
      infected plants were occasionally significantly higher than those on endophyte
      free. Cumulative foliar growth was reduced in AR1 and Nil treatments relative to
      AR37 in association with population differences of A. lentisci in both trials and
      root dry weight was reduced in one trial. In four Petri dish experiments survival
      of A. lentisci on plants infected with AR37 declined to low levels after an
      initial phase of up to 19 days during which time aphids fed and populations were
      similar to those on plants without endophyte. Aphids on AR37-infected plants
      became uncoordinated in their movement and developed tremors before dying
      suggesting a neurotoxin was responsible for their mortality. Results support the
      hypothesis that differences in A. lentisci populations due to endophyte infection
      status and strain affects plant growth.

PMID- 27695469
TI  - The Infection of Cucumber (Cucumis sativus L.) Roots by Meloidogyne incognita
      Alters the Expression of Actin-Depolymerizing Factor (ADF) Genes, Particularly in
      Association with Giant Cell Formation.
AB  - Cucumber (Cucumis sativus L.) is threatened by substantial yield losses due to
      the south root-knot nematode (Meloidogyne incognita). However, understanding of
      the molecular mechanisms underlying the process of nematode infection is still
      limited. In this study, we found that M. incognita infection affected the
      structure of cells in cucumber roots and treatment of the cytoskeleton inhibitor
      (cytochalasin D) reduced root-knot nematode (RKN) parasitism. It is known that
      Actin-Depolymerizing Factor (ADF) affects cell structure, as well as the
      organization of the cytoskeleton. To address the hypothesis that nematode-induced
      abnormal cell structures and cytoskeletal rearrangements might be mediated by the
      ADF genes, we identified and characterized eight cucumber ADF (CsADF) genes.
      Phylogenetic analysis showed that the cucumber ADF gene family is grouped into
      four ancient subclasses. Expression analysis revealed that CsADF1, CsADF2-1,
      CsADF2-2, CsADF2-3 (Subclass I), and CsADF6 (Subclass III) have higher transcript
      levels than CsADF7-1, CsADF7-2 (Subclass II genes), and CsADF5 (Subclass IV) in
      roots. Members of subclass I genes (CsADF1, CsADF2-1, CsADF2-2, and CsADF2-3),
      with the exception of CsADF2-1, exhibited a induction of expression in roots 14
      days after their inoculation (DAI) with nematodes. However, the expression of
      subclass II genes (CsADF7-1 and CsADF7-2) showed no significant change after
      inoculation. The transcript levels of CsADF6 (Subclass III) showed a specific
      induction at 21 DAI, while CsADF5 (Subclass IV) was weakly expressed in roots,
      but was strongly up-regulated as early as 7 DAI. In addition, treatment of roots
      with cytochalasin D caused an approximately 2-fold down-regulation of the CsADF
      genes in the treated plants. These results suggest that CsADF gene mediated actin
      dynamics are associated with structural changes in roots as a consequence of M.
      incognita infection.

PMID- 27695471
TI  - Editorial: Advances in Plastid Biology and Its Applications.

PMID- 27695468
TI  - The Water to Solute Permeability Ratio Governs the Osmotic Volume Dynamics in
      Beetroot Vacuoles.
AB  - Plant cell vacuoles occupy up to 90% of the cell volume and, beyond their
      physiological function, are constantly subjected to water and solute exchange.
      The osmotic flow and vacuole volume dynamics relies on the vacuole membrane -the
      tonoplast- and its capacity to regulate its permeability to both water and
      solutes. The osmotic permeability coefficient (Pf ) is the parameter that better
      characterizes the water transport when submitted to an osmotic gradient. Usually,
      Pf determinations are made in vitro from the initial rate of volume change, when
      a fast (almost instantaneous) osmolality change occurs. When aquaporins are
      present, it is accepted that initial volume changes are only due to water
      movements. However, in living cells osmotic changes are not necessarily abrupt
      but gradually imposed. Under these conditions, water flux might not be the only
      relevant driving force shaping the vacuole volume response. In this study, we
      quantitatively investigated volume dynamics of isolated Beta vulgaris root
      vacuoles under progressively applied osmotic gradients at different pH, a
      condition that modifies the tonoplast Pf . We followed the vacuole volume changes
      while simultaneously determining the external osmolality time-courses and
      analyzing these data with mathematical modeling. Our findings indicate that
      vacuole volume changes, under progressively applied osmotic gradients, would not
      depend on the membrane elastic properties, nor on the non-osmotic volume of the
      vacuole, but on water and solute fluxes across the tonoplast. We found that the
      volume of the vacuole at the steady state is determined by the ratio of water to
      solute permeabilites (Pf /Ps ), which in turn is ruled by pH. The dependence of
      the permeability ratio on pH can be interpreted in terms of the degree of
      aquaporin inhibition and the consequently solute transport modulation. This is
      relevant in many plant organs such as root, leaves, cotyledons, or stems that
      perform extensive rhythmic growth movements, which very likely involve
      considerable cell volume changes within seconds to hours.

PMID- 27695472
TI  - Does White Clover (Trifolium repens) Abundance in Temperate Pastures Determine
      Sitona obsoletus (Coleoptera: Curculionidae) Larval Populations?
AB  - To determine if host plant abundance determined the size of clover root weevil
      (CRW) Sitona obsoletus larval populations, a study was conducted over 4 years in
      plots sown in ryegrass (Lolium perenne) (cv. Nui) sown at either 6 or 30 kg/ha
      and white clover (Trifolium repens) sown at a uniform rate of 8 kg/ha. This
      provided a range of % white clover content to investigate CRW population
      establishment and impacts on white clover survival. Larval sampling was carried
      out in spring (October) when larval densities are near their spring peak at
      Lincoln (Canterbury, New Zealand) with % clover measured in autumn (April) and
      spring (September) of each year. Overall, mean larval densities measured in
      spring 2012-2015 were 310, 38, 59, and 31 larvae m-2, respectively. There was a
      significant decline in larval populations between 2012 and 2013, but spring
      populations were relatively uniform thereafter. The mean % white clover measured
      in autumns of 2012 to 2015 was 17, 10, 3, and 11%, respectively. In comparison,
      mean spring % white clover from 2012 to 2015, averaged c. 5% each year. Analysis
      relating spring (October) larval populations to % white clover measured in each
      plot in autumn (April) found the 2012 larval population to be statistically
      significantly larger in the ryegrass 6 kg/ha plots than 30 kg/ha plots.
      Thereafter, sowing rate had no significant effect on larval populations. From
      2013 to 2015, spring larval populations had a negative relationship with the
      previous autumn % white clover with the relationship highly significant for the
      2014 data. When CRW larval populations in spring 2013 to 2015 were predicted from
      the 2013 to 2015 autumn % white clover, respectively, based on their positive
      relationship in 2012, the predicted densities were substantially larger than
      those observed. Conversely, when 2015 spring larval data and % clover was
      regressed against 2012-2014 larval populations, observed densities tended to be
      higher than predicted, but the numbers came closer to predicted for the 2013 and
      2014 populations. These differences are attributed to a CRW population decline
      that was not accounted by % white clover changes, the CRW decline most likely due
      to biological control by the Braconid endoparasitoid Microctonus aethiopoides,
      which showed incremental increases in parasitism between 2012 and 2015, which in
      2015 averaged 93%.

PMID- 27695473
TI  - Genomic Identification and Expression Analysis of the Phosphate Transporter Gene
      Family in Poplar.
AB  - Inorganic phosphate is one of key macronutrients essential for plant growth. The
      acquisition and distribution of phosphate are mediated by phosphate transporters
      functioning in various physiological and biochemical processes. In the present
      study, we comprehensively evaluated the phosphate transporter (PHT) gene family
      in the latest release of the Populus trichocarpa genome (version 3.0; Phytozome
      11.0) and a total of 42 PHT genes were identified which formed five clusters:
      PHT1, PHT2, PHT3, PHT4, and PHO. Among the 42 PHT genes, 41 were localized to 15
      Populus chromosomes. Analysis of these genes led to identification of 5-14
      transmembrane segments, most of which were conserved within the same cluster. We
      identified 234 putative cis elements in the 2-kb upstream regions of the 42 PHT
      genes, many of which are related to development, stress, or hormone. Tissue
      specific expression analysis of the 42 PtPHT genes revealed that 25 were highly
      expressed in the roots of P. tremula, suggesting that most of them might be
      involved in Pi uptake. Some PtPHT genes were highly expressed in more than six of
      the twelve investigated tissues of P. tremula, while the expression of a few of
      them was very low in all investigated tissues. In addition, the expression of the
      PtPHT genes was verified by quantitative real-time PCR in four tissues of P.
      simonii. Transcripts of 7 PtPHT genes were detected in all four tested tissues of
      P. simonii. Most PtPHT genes were expressed in the roots of P. simonii at high
      levels. Further, PtPHT1.2 and PtPHO9 expression was increased under drought
      conditions, irrespective of the phosphate levels. In particular, PtPHT1.2
      expression was significantly induced by approximately 90-fold. However, the
      transcriptional changes of some PtPHT genes under drought stress were highly
      dependent on the phosphate levels. These results will aid in elucidation of the
      functions of PtPHT in the growth, development, and stress response of the poplar
      plant.

PMID- 27695474
TI  - Genome-Wide Identification, Evolution, and Co-expression Network Analysis of
      Mitogen-Activated Protein Kinase Kinase Kinases in Brachypodium distachyon.
AB  - Mitogen-activated protein kinase (MAPK) cascades are the conserved and universal
      signal transduction modules in all eukaryotes, which play the vital roles in
      plant growth, development, and in response to multiple stresses. In this study,
      we used bioinformatics methods to identify 86 MAPKKK protein encoded by 73 MAPKKK
      genes in Brachypodium. Phylogenetic analysis of MAPKKK family from Arabidopsis,
      rice, and Brachypodium has classified them into three subfamilies, of which 28
      belonged to MEKK, 52 to Raf, and 6 to ZIK subfamily, respectively. Conserved
      protein motif, exon-intron organization, and splicing intron phase in kinase
      domains supported the evolutionary relationships inferred from the phylogenetic
      analysis. And gene duplication analysis suggested the chromosomal segment
      duplication happened before the divergence of the rice and Brachypodium, while
      all of three tandem duplicated gene pairs happened after their divergence. We
      further demonstrated that the MAPKKKs have evolved under strong purifying
      selection, implying the conservation of them. The splicing transcripts expression
      analysis showed that the splicesome translating longest protein tended to be
      adopted. Furthermore, the expression analysis of BdMAPKKKs in different organs
      and development stages as well as heat, virus and drought stresses revealed that
      the MAPKKK genes were involved in various signaling pathways. And the circadian
      analysis suggested there were 41 MAPKKK genes in Brachypodium showing cycled
      expression in at least one condition, of which seven MAPKKK genes expressed in
      all conditions and the promoter analysis indicated these genes possessed many cis
      acting regulatory elements involved in circadian and light response. Finally, the
      co-expression network of MAPK, MAPKK, and MAPKKK in Brachypodium was constructed
      using 144 microarray and RNA-seq datasets, and ten potential MAPK cascades
      pathway were predicted. To conclude, our study provided the important information
      for evolutionary and functional characterization of MAPKKK family in
      Brachypodium, which will facilitate the functional analysis of BdMAPKKK genes,
      and also will facilitate better understanding the MAPK signal pathway in
      Brachypodium and beyond.

PMID- 27695475
TI  - Application of Plant-Growth-Promoting Fungi Trichoderma longibrachiatum T6
      Enhances Tolerance of Wheat to Salt Stress through Improvement of Antioxidative
      Defense System and Gene Expression.
AB  - Soil salinity is a serious problem worldwide that reduces agricultural
      productivity. Trichoderma longibrachiatum T6 (T6) has been shown to promote wheat
      growth and induce plant resistance to parasitic nematodes, but whether the plant
      growth-promoting fungi T6 can enhance plant tolerance to salt stress is unknown.
      Here, we determined the effect of plant-growth-promoting fungi T6 on wheat
      seedlings' growth and development under salt stress, and investigated the role of
      T6 in inducing the resistance to NaCl stress at physiological, biochemical, and
      molecular levels. Wheat seedlings were inoculated with the strain of T6 and then
      compared with non-inoculated controls. Shoot height, root length, and shoot and
      root weights were measured on 15 days old wheat seedlings grown either under 150
      mM NaCl or in a controlled setting without any NaCl. A number of colonies were re
      isolated from the roots of wheat seedlings under salt stress. The relative water
      content in the leaves and roots, chlorophyll content, and root activity were
      significantly increased, and the accumulation of proline content in leaves was
      markedly accelerated with the plant growth parameters, but the content of leaf
      malondialdehyde under saline condition was significantly decreased. The
      antioxidant enzymes-superoxide dismutase (SOD), peroxidase (POD), and catalase
      (CAT) in wheat seedlings were increased by 29, 39, and 19%, respectively, with
      the application of the strain of T6 under salt stress; the relative expression of
      SOD, POD, and CAT genes in these wheat seedlings were significantly up-regulated.
      Our results indicated that the strain of T6 ameliorated the adverse effects
      significantly, protecting the seedlings from salt stress during their growth
      period. The possible mechanisms by which T6 suppresses the negative effect of
      NaCl stress on wheat seedling growth may be due to the improvement of the
      antioxidative defense system and gene expression in the stressed wheat plants.

PMID- 27695476
TI  - SRBreak: A Read-Depth and Split-Read Framework to Identify Breakpoints of
      Different Events Inside Simple Copy-Number Variable Regions.
AB  - Copy-number variation (CNV) has been associated with increased risk of complex
      diseases. High-throughput sequencing (HTS) technologies facilitate the detection
      of copy-number variable regions (CNVRs) and their breakpoints. This helps in
      understanding genome structure as well as their evolution process. Various
      approaches have been proposed for detecting CNV breakpoints, but currently it is
      still challenging for tools based on a single analysis method to identify
      breakpoints of CNVs. It has been shown, however, that pipelines which integrate
      multiple approaches are able to report more reliable breakpoints. Here, based on
      HTS data, we have developed a pipeline to identify approximate breakpoints (+/-10
      bp) relating to different ancestral events within a specific CNVR. The pipeline
      combines read-depth and split-read information to infer breakpoints, using
      information from multiple samples to allow an imputation approach to be taken.
      The main steps involve using a normal mixture model to cluster samples into
      different groups, followed by simple kernel-based approaches to maximize
      information obtained from read-depth and split-read approaches, after which
      common breakpoints of groups are inferred. The pipeline uses split-read
      information directly from CIGAR strings of BAM files, without using a re
      alignment step. On simulated data sets, it was able to report breakpoints for
      very low-coverage samples including those for which only single-end reads were
      available. When applied to three loci from existing human resequencing data sets
      (NEGR1, LCE3, IRGM) the pipeline obtained good concordance with results from the
      1000 Genomes Project (92, 100, and 82%, respectively). The package is available
      at https://github.com/hoangtn/SRBreak, and also as a docker-based application at
      https://registry.hub.docker.com/u/hoangtn/srbreak/.

PMID- 27695478
TI  - In Papyro Comparison of TMM (edgeR), RLE (DESeq2), and MRN Normalization Methods
      for a Simple Two-Conditions-Without-Replicates RNA-Seq Experimental Design.
AB  - In the past 5 years, RNA-Seq has become a powerful tool in transcriptome analysis
      even though computational methods dedicated to the analysis of high-throughput
      sequencing data are yet to be standardized. It is, however, now commonly accepted
      that the choice of a normalization procedure is an important step in such a
      process, for example in differential gene expression analysis. The present
      article highlights the similarities between three normalization methods: TMM from
      edgeR R package, RLE from DESeq2 R package, and MRN. Both TMM and DESeq2 are
      widely used for differential gene expression analysis. This paper introduces
      properties that show when these three methods will give exactly the same results.
      These properties are proven mathematically and illustrated by performing in
      silico calculations on a given RNA-Seq data set.

PMID- 27695479
TI  - Global environmental change: local perceptions, understandings, and explanations.
AB  - Global environmental change (GEC) is an increasingly discussed phenomenon in the
      scientific literature as evidence of its presence and impacts continues to grow.
      Yet, while the documentation of GEC is becoming more readily available, local
      perceptions of GEC- particularly in small-scale societies-and preferences about
      how to deal with it, are still largely overlooked. Local knowledge and
      perceptions of GEC are important in that agents make decisions (including on
      natural resource management) based on individual perceptions. We carried out a
      systematic literature review that aims to provide an exhaustive state-of-the-art
      of the degree to and manner in which the study of local perceptions of change are
      being addressed in GEC research. We reviewed 126 articles found in peer-reviewed
      journals (between 1998 and 2014) that address local perceptions of GEC. We used
      three particular lenses of analysis that are known to influence local
      perceptions, namely (i) cognition, (ii) culture and knowledge, and (iii)
      possibilities for adaptation.We present our findings on the geographical
      distribution of the current research, the most common changes reported, perceived
      drivers and impacts of change, and local explanations and evaluations of change
      and impacts. Overall, we found the studies to be geographically biased, lacking
      methodological reporting, mostly theory based with little primary data, and
      lacking of indepth analysis of the psychological and ontological influences in
      perception and implications for adaptation. We provide recommendations for future
      GEC research and propose the development of a "meta-language" around adaptation,
      perception, and mediation to encourage a greater appreciation and understanding
      of the diversity around these phenomena across multiple scales, and improved
      codesign and facilitation of locally relevant adaptation and mitigation
      strategies.

PMID- 27695477
TI  - Differential Protein Distribution between the Nucleus and Mitochondria:
      Implications in Aging.
AB  - The coordination of nuclear and mitochondrial genomes plays a pivotal role in
      maintenance of mitochondrial biogenesis and functionality during stress and
      aging. Environmental and cellular inputs signal to nucleus and/or mitochondria to
      trigger interorganellar compensatory responses. Loss of this tightly orchestrated
      coordination results in loss of cellular homeostasis and underlies various
      pathologies and age-related diseases. Several signaling cascades that govern
      interorganellar communication have been revealed up to now, and have been
      classified as part of the anterograde (nucleus to mitochondria) or retrograde
      (mitochondrial to nucleus) response. Many of these molecular pathways rely on the
      dual distribution of nuclear or mitochondrial components under basal or stress
      conditions. These dually localized components usually engage in specific tasks in
      their primary organelle of function, whilst upon cellular stimuli, they appear in
      the other organelle where they engage in the same or a different task, triggering
      a compensatory stress response. In this review, we focus on protein factors
      distributed between the nucleus and mitochondria and activated to exert their
      functions upon basal or stress conditions. We further discuss implications of bi
      organellar targeting in the context of aging.

PMID- 27695481
TI  - Protective effects of hesperidin in experimental testicular ischemia/reperfusion
      injury in rats.
AB  - INTRODUCTION: In this study, we aimed to determine the protective effects of
      hesperidin, a citrus flavonoid, in a model of testicular ischemia/reperfusion
      injury in rats. MATERIAL AND METHODS: Forty-two pubertal male Wistar-Albino rats
      were divided into six groups: group 1 - control; group 2 - 50 mg/kg hesperidin
      (low dose hesperidin) used without torsion (LH group); group 3 - 100 mg/kg
      hesperidin without torsion (HH group); group 4 - torsion/detorsion group (T/D);
      group 5 - T/D + 50 mg/kg hesperidin treatment group (T/D + LH); and group 6 - T/D
      + 100 mg/kg hesperidin treatment group (T/D + HH). Hesperidin was given to the
      treatment groups 30 min before detorsion. After the fourth hour of reperfusion,
      orchiectomy was performed on the rats under anesthesia. The tissue samples were
      examined histologically and biochemically. RESULTS: In the T/D group testicular
      malondialdehyde (MDA) levels were increased significantly (p < 0.001) whereas
      superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels were
      decreased compared to the control and other groups. However, hesperidin caused
      the effect of T/D to become closer to normal biochemical values. In addition, the
      histological examinations showed that T/D caused damage in the testis but
      hesperidin reduced this effect. The effects of hesperidin were found to be dose
      dependent. Thus, applying high doses would generate greater therapeutic effects.
      CONCLUSIONS: In a rat testicular T/D model we observed biochemical and
      histological damage due to ischemia. However, high and low dose applications of
      hesperidin were shown to have protective effects against this damage. Therefore,
      the aforementioned citrus flavonoid may provide positive results in cases of
      testicular torsion.

PMID- 27695480
TI  - Meroxest improves the prognosis of immunocompetent C57BL/6 mice with allografts
      of E0771 mouse breast tumor cells.
AB  - INTRODUCTION: Recently, we have reported the antitumor properties of a new family
      of synthetic merosesquiterpenes, among which meroxest is highlighted, since it
      has high activity and specificity for ER+ breast cancer cells. In this paper, we
      characterize allografts of ER+ E0771 mouse breast tumor cells in immunocompetent
      C57BL/6 mice, and also analyze the effect of meroxest on the prognosis of the
      disease. MATERIAL AND METHODS: Twenty female C57BL/6 mice were injected with 106
      E0771 cells. Once the tumors reached the appropriate size, the mice were divided
      into two groups, one control and another treated orally with 15 mg/kg of
      meroxest. After 20 days, tumor samples were taken for histopathological study and
      for determination of the expression of the prognostic markers Ki67 and vascular
      endothelial growth factor (VEGF) by immunofluorescence. RESULTS: In sections
      stained with hematoxylin-eosin, we observed that tumors have a well-defined
      capsule enclosing E0771 tumor cells. The central area of tumors contains necrotic
      regions with leukocyte infiltration. Meroxest treatment significantly reduces
      tumor size (68%, p < 0.05), induces changes in its structure, decreases the
      degree of leukocyte infiltration, and significantly reduces the expression of
      Ki67 (33%, p < 0.05) and VEGF (82%, p < 0.05). CONCLUSIONS: Meroxest improves the
      prognosis of mice since it reduces leukocyte infiltration, and decreases the
      expression of Ki67 and VEGF markers. Consequently, the merosesquiterpene could
      become a useful antiangiogenic drug in the treatment of breast cancer. These
      results encourage us to deepen the study of meroxest, in order to find more
      evidence that supports the convenience of its evaluation in a clinical study or
      trial.

PMID- 27695482
TI  - The effects of treadmill exercise on penicillin-induced epileptiform activity.
AB  - INTRODUCTION: The aim of this study was to evaluate the effects of short-,
      moderate- and long-duration treadmill exercise (15, 30 and 60 min) on the mean
      frequency and amplitude of penicillin-induced epileptiform activity in rats.
      MATERIAL AND METHODS: In this study, 32 rats were assigned to 15, 30, and 60 min
      running exercise groups and the control group, each consisting of 8 rats.
      According to the specified protocol, the rats were submitted to running exercises
      at the same hour of each day for 90 days. After the exercise program, the rats
      were administered (500 IU/2.5 ul) of penicillin into the left cortex by the
      microinjection method. An electrocorticogram (ECoG) recording was performed for 3
      h using a data acquisition system. The frequency and the amplitude of the
      recordings were analyzed. RESULTS: Short-duration treadmill exercise (15 min)
      caused a decrease in the frequency of penicillin-induced epileptiform activity at
      70 min after penicillin injection (p < 0.001). The mean frequency of epileptiform
      activity decreased at 90 min after penicillin injection in the 30 and 60 min
      treadmill exercise groups (p < 0.01). The mean amplitude of epileptiform activity
      was not changed in any of the exercise groups compared to the control (p > 0.05).
      CONCLUSIONS: The results of the present study demonstrate for the first time that
      short-, moderate- and long-duration treadmill exercises decreased the frequency
      of penicillin-induced epileptiform activity. These findings may contribute to
      improving the quality of life in epileptic patients.

PMID- 27695484
TI  - NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis.
AB  - INTRODUCTION: Pattern recognition receptor-mediated signaling pathways have
      recently been elucidated to bridge the innate immune system and atherosclerosis.
      NLRP3 is a member of the NLR family. Upon activation, it initiates IL-1beta and
      IL-18 processing, a key step in the inflammatory process of atherosclerosis.
      MATERIAL AND METHODS: We used three different types of lipoproteins, ox-LDL, ox
      HDL, and HDL, in Thp-1 at the concentration of 50 mg/l, 100 mg/l, and 150 mg/l
      respectively. Using real-time polymerase chain reaction and western blot, ELISA
      detected the expression of NLRP3 and downstream cytokines. NLRP3 siRNA was
      constructed to down-regulate expression of the NLRP3 gene via the RNA
      interference technique. 150 mg/l of ox-LDL, ox-HDL and HDL was added to the Thp-1
      cell line respectively. We observed the changes in the expression of caspase-1,
      IL-1beta and IL-18 when the NLRP3 gene was down-regulated. RESULTS: Ox-LDL and ox
      HDL addition not only increases the expression of NLRP3, but also activates the
      NLRP3 downstream cytokines and caspase-1 and induces IL-1beta and IL-18
      secretion. Moreover, the effects of activation and induction are shown to have a
      dose-dependent manner. Expression of NLRP3 and its downstream inflammatory
      cytokines is reduced in the presence of HDL (p < 0.05). Furthermore, our data
      demonstrated that NLRP3 siRNA downregulates NLRP3 expression in mononuclear
      cells, thus leading to a dramatic reduction in the expression of caspase-1, IL
      1beta and IL-18 (p < 0.05). CONCLUSIONS: The data suggest that activation of the
      NLRP3 inflammasome is a critical step in caspase-1 activation and IL-1beta and IL
      18 secretion. Interference with the NLRP3 inflammasome can significantly inhibit
      the generation of cytokines, thus impeding the pathogenesis of inflammation.

PMID- 27695483
TI  - Effect of a local, one time, low-dose injection of zoledronic acid on titanium
      implant osseointegration in ovariectomized rats.
AB  - INTRODUCTION: Local application of bisphosphonates has been proven to be safer
      than systemic administration to promote implant fixation. The objective of this
      study was to introduce such a simple, convenient and efficient method to enhance
      titanium (Ti) implant osseointegration in ovariectomized (OVX) rats. MATERIAL AND
      METHODS: Twenty female Sprague-Dawley rats sequentially underwent bilateral
      ovariectomy and tibia implantation, and injection of 30 ug/implant zoledronic
      acid (ZOL) at the site of implantation was performed. At the end of the study,
      the tibiae, mandibles, femurs and vertebrae were harvested for dual energy X-ray
      absorptiometry, histology and micro-computed tomography examination. RESULTS:
      Ovariectomized rats showed poor bone density, bone mass and trabecular
      microstructure. OVX + ZOL rats were characterized by significantly improved peri
      implant bone area (1.72-fold), bone contact (2.30-fold), bone mineral density
      (1.57-fold) and bone mineral content (1.67-fold), as well as moderately increased
      bone volume to total volume ratio (1.34-fold), percentage osteointegration (1.54
      fold), connectivity density (1.45-fold), and trabecular number (1.43-fold), but
      decreased trabecular separation (57.69%) when compared with the control levels (p
      < 0.05). No histological signs of jaw osteonecrosis were observed in the rats
      treated with ZOL, and there was no significant difference between the OVX group
      and OVX + ZOL group in the bone mass of the mandible, femur and 5th lumbar
      vertebra (p > 0.05). In addition, the overproduction of osteoporosis-induced
      advanced glycation end-products (AGEs) was completely prevented by local
      treatment with 30 ug/implant ZOL. CONCLUSIONS: A local, one time, low-dose
      injection of ZOL at the site of implantation is able to promote the
      osseointegration of Ti implants following postmenopausal osteoporosis, and this
      action may be partly mediated by inhibition of the osteoporosis-induced AGE
      overproduction in the bone marrow.

PMID- 27695485
TI  - Effects of Porphyromonas gingivalis lipopolysaccharide on the expression of key
      genes involved in cholesterol metabolism in macrophages.
AB  - INTRODUCTION: Cardiovascular diseases are positively correlated with periodontal
      disease. However, the molecular mechanisms linking atherosclerosis and
      periodontal infection are not clear. This study aimed to determine whether
      Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) altered the expression of
      genes regulating cholesterol metabolism in macrophages in the presence of low
      density lipoprotein (LDL). MATERIAL AND METHODS: THP-1-derived macrophages were
      exposed to different concentrations (0.1, 1, 10 ug/ml) of LPS in the presence of
      50 ug/ml native LDL. Macrophages were also incubated with 1 ug/ml LPS for varying
      times (0, 24, 48, or 72 h) in the presence of native LDL. Foam cell formation was
      determined by oil red O staining and cholesterol content quantification. CD36,
      lectin-like oxidized LDL receptor-1 (LOX-1), ATP-binding cassette G1 (ABCG1), and
      acetyl CoA acyltransferase 1 (ACAT1) expression levels were measured by western
      blot and qRT-PCR. RESULTS: Foam cell formation was induced in a time- and
      concentration-dependent manner as assessed by both morphological and biochemical
      criteria. Pg-LPS caused downregulation of CD36 and ABCG1 but upregulation of
      ACAT1, while LOX-1 expression was not affected (p = 0.137). CONCLUSIONS: Pg-LPS
      appears to be an important link in the development of atherosclerosis by
      mechanisms targeting cholesterol homeostasis, namely, excess cholesterol ester
      formation via ACAT1 and reduced cellular cholesterol efflux via ABCG1.

PMID- 27695486
TI  - Expression of candidate genes associated with obesity in peripheral white blood
      cells of Mexican children.
AB  - INTRODUCTION: Obesity is a chronic, complex, and multifactorial disease,
      characterized by excess body fat. Diverse studies of the human genome have led to
      the identification of susceptibility genes that contribute to obesity. However,
      relatively few studies have addressed specifically the association between the
      level of expression of these genes and obesity. MATERIAL AND METHODS: We studied
      160 healthy and obese unrelated Mexican children aged 6 to 14 years. We measured
      the transcriptional expression of 20 genes associated with obesity, in addition
      to the biochemical parameters, in peripheral white blood cells. The detection of
      mRNA levels was performed using the OpenArray Real-Time PCR System (Applied
      Biosystems). RESULTS: Obese children exhibited higher values of fasting glucose
      (p = 0.034), fasting insulin (p = 0.004), low-density lipoprotein (p = 0.006),
      triglycerides (p < 0.001), systolic blood pressure and diastolic blood pressure
      (p < 0.001), and lower values of high-density lipoprotein (p < 0.001) compared to
      lean children. Analysis of transcriptional expression data showed a difference
      for ADRB1 (p = 0.0297), ADIPOR1 (p = 0.0317), GHRL (p = 0.0060) and FTO (p =
      0.0348) genes. CONCLUSIONS: Our results suggest that changes in the expression
      level of the studied genes are involved in biological processes implicated in the
      development of childhood obesity. Our study contributes new perspectives for a
      better understanding of biological processes involved in obesity. The protocol
      was approved by the National Committee and Ethical Committee Board from the
      Mexican Social Security Institute (IMSS) (IMSS FIS/IMSS/PRIO/10/011).

PMID- 27695487
TI  - Increased chitotriosidase activity in plasma of patients with type 2 diabetes.
AB  - INTRODUCTION: Chitotriosidase (CHIT1) is a chitinolytic enzyme involved mainly in
      the immune and inflammatory response. It shows increased activity in many
      pathologies, including in newly diagnosed type 2 diabetes (T2D). This study aimed
      to investigate this enzyme's activity in plasma of patients with ongoing T2D and
      indicate factors related to the increased activity of this enzyme. MATERIAL AND
      METHODS: Ninety-one patients and 46 control subjects without abnormalities in
      carbohydrate metabolism and inflammatory states were enrolled in the study.
      Plasma CHIT1 activity was measured by a spectrofluorometric method. Routine
      laboratory parameters such as blood glucose, total cholesterol and HDL fraction,
      triglyceride, glycated hemoglobin, white blood cell count and C-reactive protein
      were measured by standard methods. RESULTS: We found that the chitotriosidase
      activity was significantly higher (p < 0.001) in type 2 diabetic patients and
      positively associated with parameters of glycemic control (levels of glucose and
      glycated hemoglobin) and blood pressure. Plasma glucose level and systolic blood
      pressure were independent determinants of increased CHIT1 activity in T2D
      patients, even after adjustment for disease duration, body mass index, parameters
      of inflammation and lipid metabolism. We also found that increased CHIT1 activity
      was associated with occurrence of diabetic angiopathies. CONCLUSIONS: This
      investigation indicates a possible role of chitotriosidase in the course of T2D,
      especially in relation to development of diabetic angiopathies.

PMID- 27695488
TI  - PROGENS-HbA1c study: safety and effectiveness of premixed recombinant human
      insulin (Gensulin M30).
AB  - INTRODUCTION: Insulin analogues have gained widespread popularity. However, in
      many countries the use of these drugs is limited by their relatively high cost,
      so there is still a need for more cost-effective human insulin therapies. The aim
      of the study was to assess the effectiveness and safety of the premixed
      recombinant human insulin (rhuI) Gensulin M30 in a real-life setting. MATERIAL
      AND METHODS: The study group consisted of 4257 patients (2196 female, 2061 male)
      with type 2 diabetes, aged 63.7 +/-9.4, with body mass index (BMI) 30.3 +/-4.5
      kg/m2 and diabetes duration 9 +/-5.5 years. All patients were treated with
      premixed rhuI Gensulin M30. In 91.7% of patients, insulin was used in combination
      with metformin. In 3.7% of patients, it was used with sulphonylureas. The
      patients were observed for a period of 6 months. RESULTS: The total insulin dose
      on visit 1 was 36.1 +/-18.7 U (0.42 +/-0.22 U/kg), and by the end of the study it
      reached 40.3 +/-18.9 U (0.48 +/-0.22 U/kg). A significant, continuous decrease of
      the levels of glycated hemoglobin (HbA1c), along with fasting and postprandial
      plasma glucose, was observed during the study period. The frequency of
      hypoglycemia increased slightly during the study, although these figures remained
      low, especially with regard to severe hypoglycemic episodes (0.02
      episodes/patient/year). The lowest number of hypoglycemic episodes occurred in
      patients treated with insulin and metformin, while the highest number of episodes
      was observed in patients treated with insulin alone. No weight changes were noted
      in the patients during the study. CONCLUSIONS: This study shows rhuI Gensulin M30
      to be effective and safe in a real-life setting.

PMID- 27695489
TI  - The effect of hyperoxia on central blood pressure in healthy subjects.
AB  - INTRODUCTION: Hyperoxia increases total peripheral resistance by acting locally
      but also inhibits the activity of carotid body chemoreceptors. We studied the
      effect of hyperoxia on central pressure in normotensive subjects. MATERIAL AND
      METHODS: Medical air followed by 100% oxygen was provided to 19 subjects (12/7
      female/male, age 28.2 +/-1.1 years) for 15 min through a non-rebreather mask.
      Central blood pressure was then measured using applanation tonometry. RESULTS:
      After the first 2 min of hyperoxia, heart rate decreased significantly (65 +/-2.6
      beats/min vs. 61 +/-2.1 beats/min, p = 0.0002). Peripheral and central blood
      pressure remained unchanged, while hemoglobin oxygen saturation and
      subendocardial viability ratio index increased (97 +/-0.4% vs. 99 +/-0.2%, p =
      0.03; 168 +/-8.4% vs. 180 +/-8.2%, p = 0.009). After 15 min of 100% oxygen
      ventilation, heart rate and peripheral and central blood pressures remained
      unchanged from the first 2 min. The augmentation index, augmentation pressure and
      ejection duration increased as compared to baseline values and those obtained at
      2 min (-5.1 +/-2.9% vs. -1.2 +/-2.6%, p = 0.005 and -4.6 +/-2.7% vs. -1.2 +/
      2.6%, p = 0.0015; -1.3 +/-0.7 mm Hg vs. -0.2 +/-1.2 mm Hg, p = 0.003 and -1.1 +/
      0.7 mm Hg vs. -0.2 +/-1.2 mm Hg, p = 0.012; 323 +/-3.6 ms vs. 330 +/-3.5 ms, p =
      0.0002 and 326 +/-3.5 ms vs. 330 +/-3.5 ms, p = 0.021, respectively).
      CONCLUSIONS: The present study shows that hyperoxia does not affect central blood
      pressure in young healthy subjects and may improve myocardial blood supply
      estimated indirectly from applanation tonometry.

PMID- 27695490
TI  - Activated factor IX, factor XI and tissue factor identify patients with permanent
      atrial fibrillation treated with warfarin who are at risk of ischemic stroke.
AB  - INTRODUCTION: Previously, we have demonstrated that significant proportions of
      patients with various cardiovascular diseases have active tissue factor and
      active factor XIa in their plasma. In the current study, we evaluated active
      tissue factor and active factors (F)XI and FIX in plasma from patients with
      atrial fibrillation. MATERIAL AND METHODS: In 110 consecutive patients with
      permanent atrial fibrillation receiving warfarin, we determined active tissue
      factor, together with plasma FIXa and FXIa, using clotting assays by measuring
      the response to inhibitory monoclonal antibodies. RESULTS: Sixteen (14.5%)
      patients had detectable active tissue factor and active FXIa, including 11
      subjects with both factors, while FIXa was observed in 28 (25.7%) patients. The
      three positive groups did not differ from the patients without these factors with
      regard to demographic and clinical characteristics. Von Willebrand factor was
      higher in the active tissue factor-positive group (p < 0.0001) and FXIa-positive
      group (p = 0.0037). Individuals positive for active tissue factor and FXIa had
      higher plasma interleukin-6 levels (p = 0.0014 and 0.0322, respectively). The
      presence of active tissue factor, FXIa and FIXa in anticoagulated patients with
      permanent atrial fibrillation correlated with elevated von Willebrand factor and
      interleukin-6. During a 3-year follow-up, ischemic stroke (n = 12, 10.9%)
      occurred more commonly among atrial fibrillation patients who had circulating TF
      (p = 0.002) or FXIa (p = 0.013). CONCLUSIONS: These data suggest that circulating
      active coagulation factors, in particular TF and FXIa, can be detected despite
      oral anticoagulation in a significant proportion of patients with atrial
      fibrillation, and could represent novel markers of persistent prothrombotic
      alterations predisposing to ischemic stroke.

PMID- 27695491
TI  - Tricuspid annulus plane systolic excursion (TAPSE) has superior predictive value
      compared to right ventricular to left ventricular ratio in normotensive patients
      with acute pulmonary embolism.
AB  - INTRODUCTION: Right ventricular dysfunction (RVD) is an indicator of poor
      prognosis in normotensive patients with acute pulmonary embolism (APE). The aim
      of this study was to compare right ventricular (RV)/left ventricular (LV) ratio
      measured by echocardiography and multidetector computed tomography (MDCT) with
      tricuspid annulus plane systolic excursion (TAPSE) as a prognostic factor of APE
      related 30-day mortality. MATERIAL AND METHODS: We examined 76 patients with
      confirmed APE, hemodynamically stable at admission. We evaluated the prognostic
      value of RV/LV ratio in the apical 4-chamber view and TAPSE measured at
      echocardiography and the MDCT RV/LV ratio. RESULTS: Thirty-day APE-related
      mortality was 10.5% (8 patients). The area under the curve (AUC) for TAPSE in the
      prediction of APE-related mortality was higher (p < 0.00001) (0.905, 95% CI:
      0.828-0.983) than the AUC of the echo RV/LV ratio (0.427, 95% CI: 0.183-0.672)
      and MDCT RV/LV ratio (0.371, 95% CI: 0.145-0.598). In univariable Cox analysis,
      TAPSE was the only significant mortality predictor, with hazard ratio (HR) 0.73
      (95% CI: 0.62-0.87, p = 0.0004). In multivariable Cox analysis TAPSE was the only
      significant mortality predictor, with HR 0.62 (95% CI: 0.46-0.85; p = 0.003),
      while age, heart rate, and RV/LV ratio in echo or MDCT were non-significant.
      TAPSE <= 15 mm was a significant predictor of APE-related mortality, with HR 26.2
      (95% CI: 3.2-214.1; p = 0.002), PPV 44% and NPV 98%. CONCLUSIONS: The TAPSE is
      preferable to echo and MDCT RV/LV ratio for risk stratification in initially
      normotensive patients with APE. The TAPSE <= 15 mm identifies patients with an
      increased risk of 30-day APE-related mortality.

PMID- 27695492
TI  - Subclinical cardiovascular disease markers and vitamin D deficiency in non
      dialysis chronic kidney disease patients.
AB  - INTRODUCTION: Since 25-hydroxyvitamin D (25(OH)D) deficiency has been linked to
      an increased risk for cardiovascular disease (CVD) in the hemodialysis
      population, we aimed to determine the relationship between serum 25(OH)D level
      and markers of subclinical CVD in non-dialysis chronic kidney disease (CKD)
      patients. MATERIAL AND METHODS: This cross-sectional, single-center study
      prospectively enrolled 87 clinically stable CKD patients (median age: 61 (57-66)
      years, 51% male, median estimated glomerular filtration rate (eGFR): 32 (27-37)
      ml/min). Five markers of subclinical CVD were assessed: intima-media thickness,
      abdominal aortic calcifications (AAC) using the Kauppila score, cardio-ankle
      vascular index, ankle-brachial index (ABI) and interventricular septum thickness.
      RESULTS: Vascular (37%), glomerular (23%) and interstitial (18%) nephropathies
      were the main causes of CKD. 25(OH)D had a median value of 14 (12.5-17.1) ng/ml,
      and its levels decreased with eGFR (rs = 0.19; p = 0.04). Patients with 25(OH)D
      deficiency (54%) were older, had a higher serum alkaline phosphatase level, lower
      ABI and higher AAC score. There were no differences between the two groups
      regarding other traditional or non-traditional risk factors for atherosclerosis.
      The association between subclinical CVD markers and 25(OH)D was further evaluated
      in multivariable binomial logistic regression models adjusted for CV risk
      factors. Lower 25(OH)D level was retained as an independent predictor only for
      pathological ABI. CONCLUSIONS: This is the first study to evaluate the
      relationship between a large set of subclinical CVD markers and 25(OH)D
      deficiency in non-dialysis CKD patients. We found that hypovitaminosis D is
      associated with subclinical peripheral arterial disease, independently of other
      cardiovascular risk factors.

PMID- 27695493
TI  - Congenital duodenal obstruction with delayed presentation: seven years of
      experience.
AB  - INTRODUCTION: The duodenum is the most common site for congenital intestinal
      obstruction. The duodenal web with a central hole can present without any overt
      signs of obstruction at a later age. MATERIAL AND METHODS: Over a 7-year period,
      children with congenital intestinal obstruction were identified in this study.
      The complications and operative findings of patients with duodenal web with
      conditions such as wind sock deformity and delayed diagnosis were evaluated in
      this study. RESULTS: This study included 81 infants with congenital intestinal
      obstruction. At operation, 48 patients demonstrated duodenal obstruction with
      atresia in 27, annular pancreas in 15 and malrotation in 6. Also, we observed
      incomplete obstruction of the duodenum due to a fenestrated web in 8 patients.
      The age of these patients at operation time ranged from 5 days to 72 months.
      Fifty percent of affected patients were associated with trisomy 21, all of whom
      exhibited failure to thrive due to food intolerance. The patients older than 2
      years presented with major complications of gastroesophageal reflux such as
      esophageal ulcer, stricture and dysphagia. Additionally we had a unique case of a
      patient who had been referred with an epigastric mass. During the operation, we
      found 440 seeds of various fruits in the stomach and the first portion of the
      duodenum. CONCLUSIONS: Our study emphasizes that duodenal web with a central hole
      can present without signs of obstruction at a later age with only failure to
      thrive and food intolerance. Therefore a high index of suspicion is necessary for
      diagnosis when it presents beyond the usual age.

PMID- 27695494
TI  - Socioeconomic determinants of prostate-specific antigen testing and estimation of
      the prevalence of undiagnosed prostate cancer in an elderly Polish population
      based on the PolSenior study.
AB  - INTRODUCTION: Socioeconomic determinants of prostate-specific antigen (PSA)
      testing and prevalence of undiagnosed prostate cancer (PCa) in the Polish
      population are poorly understood. The aim of this study was to identify factors
      associated with PSA testing in elderly Polish men, and estimate the size of the
      population at risk of PCa related to PSA non-testing. MATERIAL AND METHODS: We
      analyzed questionnaire-derived data concerning PSA testing, obtained in 2567
      elderly and 332 younger (age: 55-59) participants of the population-based
      PolSenior study. Additionally, PSA was measured in 2414 subjects. RESULTS: The
      PSA had previously been tested in 41.2% of elderly and in 24.8% of younger
      participants. Non-smoking status (OR = 2.06, p < 0.001), higher personal income
      (OR = 1.56, p < 0.001), better education (OR = 1.49, p = 0.001), previous white
      collar work (OR = 1.37, p = 0.005), alcohol abstinence (OR = 1.28, p = 0.02),
      married status (OR = 1.24, p = 0.04), dependence in Instrumental Activities of
      Daily Living (IADL) but not in Activities of Daily Living (ADL) (OR = 0.65, p <
      0.001), and dependence in ADL (OR = 0.55, p < 0.001) were independent predictors
      of previous PSA testing in elderly participants. There were 31 elderly previously
      treated for PCa (calculated standardized prevalence: 935 per 100,000 elderly
      population). The PSA levels > 4 ng/ml were found in 12.8% of 65-74-year-old and
      4.5% of 55-59-year-old previously non-tested participants. We calculated the
      standardized prevalence rate of undiagnosed PCa as approximately 1370 and 2352
      cases per 100,000 population aged 55-59 and 65-74 years, respectively.
      CONCLUSIONS: In Poland, 58.8% of elderly men have never had PSA tested. These
      were less likely to be functionally independent, married, better educated, non
      smokers or to have previous office employment or higher than average personal
      income. Our data suggest substantial underdiagnosis of prostate cancer among
      Polish men.

PMID- 27695495
TI  - Dialkylcarbamoyl chloride-impregnated dressing for the prevention of surgical
      site infection in women undergoing cesarean section: a pilot study.
AB  - INTRODUCTION: Incisional surgical site infections (SSIs) occur in approximately
      1.8-9.2% of patients undergoing cesarean section (CS) and contribute to prolonged
      hospitalization time and increased treatment costs. Dressings impregnated with
      dialkylcarbamoyl chloride (DACC) are an innovative approach to wound treatment
      based on a solely physical mechanism of action, and therefore can be used safely
      and without time restrictions in women during the puerperal and lactation period.
      MATERIAL AND METHODS: A single-blinded randomized, controlled pilot study was
      conducted at the Mazovian Brodno Hospital, a tertiary care hospital, between
      December 2013 and March 2014, and it evaluated the presence of superficial and
      deep SSIs in patients during the first 14 days after a CS. Patients were randomly
      allocated to receive treatment with either a DACC dressing or a standard surgical
      dressing. RESULTS: One hundred and forty-two patients after planned or emergency
      CS were enrolled in the study. No significant differences between the groups were
      observed with regard to patients' basic demographic and perioperative
      characteristics. The rate of superficial and deep SSIs was 2.8% in the group of
      patients who received a DACC dressing compared to 9.8% in the group with a
      standard surgical dressing (p = 0.08). Patients with SSIs who received a standard
      surgical dressing required systemic antibiotic therapy significantly more
      frequently (p = 0.03). Based on the logistic regression model developed, the pre
      pregnancy body mass index was the only statistically significant risk factor for
      SSI (p = 0.015). CONCLUSIONS: The results of the pilot study indicate a
      decreasing tendency of the SSI rate in patients after a CS who received DACC
      impregnated dressings.

PMID- 27695497
TI  - Evaluation of medical and psychological parameters of quality of life in
      supraventricular tachyarrhythmia children. A comparison with healthy children.
AB  - INTRODUCTION: There are only a few available studies evaluating quality of life
      (QoL) in pediatric patients with cardiac arrhythmia. The aim of the study was to
      evaluate medical and psychological parameters of the QoL in children with a
      diagnosed supraventricular tachyarrhythmia (SVT) and to compare the obtained data
      with a group of healthy children (HC). MATERIAL AND METHODS: Inclusion criteria:
      children aged 7-18 with SVT, treated at Poznan University of Medical Sciences,
      Department of Pediatric Cardiology. The evaluation tools were the WHOQOL-BREF
      instrument and a questionnaire related to the patient's feelings and observations
      concerning arrhythmia (Pediatric Arrhythmia Related Score - PARS), developed by
      the authors and adjusted to the group of arrhythmia patients. RESULTS: The study
      included 180 SVT children and 83 HC. On the basis of WHOQOL-BREF the SVT group
      was found to have lower assessment values of QoL within the physical domain (Phd)
      (mean +/- SD: 65.7 +/-15.8 vs. 81.6 +/-12.8; p < 0.0001) and psychological domain
      (Psd) (mean +/- SD: 75.8 +/-15.2 vs. 81.3 +/-14.1; p < 0.005). No significant
      differences were found within the social relationships domain or the environment
      domain. On the basis of PARS in the SVT group the patients reported significantly
      increased symptoms within Phd (mean +/- SD: 2.3 +/-0.7 vs. 1.6 +/- 0.3; p <
      0.0001) as well as increased negative feelings within Psd (mean +/- SD: 2.3 +/
      0.7 vs. 2.1 +/- 0.6; p < 0.005). CONCLUSIONS: Medical and psychological
      parameters of the QoL in SVT children are significantly lower in comparison with
      HC. A diagnosis of SVT has no influence on the social and environmental areas of
      QoL. The PARS appears to be a useful tool to supplement the generic questionnaire
      for QoL evaluation in SVT children.

PMID- 27695496
TI  - Prediction of incidence and bio-psycho-socio-cultural risk factors of post-partum
      depression immediately after birth in an Iranian population.
AB  - INTRODUCTION: Post-partum depression (PPD) is the most prevalent mental problem
      associated with childbirth. The purpose of the present study was to determine the
      incidence of early PPD and possible relevant risk factors among women attending
      primary health centers in Mazandaran province, Iran for the first time. MATERIAL
      AND METHODS: A longitudinal cohort study was conducted among 2279 eligible women
      during weeks 32-42 of pregnancy to determine bio-psycho-socio-cultural risk
      factors of depression at 2 weeks post-partum using the Iranian version of the
      Edinburgh Postnatal Depression Scale (EPDS). Univariate and hierarchical multiple
      logistic regression models were used for data analysis. RESULTS: Among 1,739
      mothers whose EPDS scores were <= 12 during weeks 32-42 of gestation and at the
      follow-up study, the cumulative incidence rate of depression was 6.9% (120/1,739)
      at 2 weeks post-partum. In the multivariate model the factor that predicted
      depression symptomatology at 2 weeks post-partum was having psychiatric distress
      in pregnancy based on the General Health Questionnaire (GHQ) (OR = 1.06, (95% CI:
      1.04-1.09), p = 0.001). The risk of PPD also lower in those with sufficient
      parenting skills (OR = 0.78 (95% CI: 0.69-0.88), p = 0.001), increased marital
      satisfaction (OR = 0.94 (95% CI: 0.9-0.99), p = 0.03), increased frequency of
      practicing rituals (OR = 0.94 (95% CI: 0.89-0.99), p = 0.004) and in those whose
      husbands had better education (OR = 0.03 (95% CI: 0.88-0.99), p = 0.04).
      CONCLUSIONS: The findings indicated that a combination of demographic,
      sociological, psychological and cultural risk factors can make mothers vulnerable
      to PPD.

PMID- 27695498
TI  - Magnetic resonance imaging of neonates in the magnetic resonance compatible
      incubator.
AB  - INTRODUCTION: The authors present the first experience in neonatal magnetic
      resonance imaging (MRI) examinations using an MR compatible incubator (INC) at
      the Institute of Mother and Child. MATERIAL AND METHODS: Forty-nine examinations
      of 47 newborns (20 girls, 27 boys) were performed using the GE Signa HDxt 1.5T
      system and INC Nomag IC 1.5. Demographic data, anesthetic methods and MRI
      findings in the INC in comparison with previously performed imaging were
      analyzed. RESULTS: Thirty-two neonates were prematurely born (68.1%) at
      gestational age 23-37 weeks, mean: 29.9 weeks. They were examined at 26 weeks
      postmenstrual age to 1 month corrected age, mean: 37.5 weeks. Body weight of
      newborns on the study day was 600-4300 g, mean: 2724 g. Seventeen (34.7%)
      children were examined in physiological sleep, 32 (65.3%) anesthetized. In none
      of them did anesthesiological complications or disease worsening occur. In 43
      (91.5%) children brain MRI was performed, in 4 (8.5%) MRI of the spinal cord and
      canal and of the abdomen/pelvis. In children prenatally examined by MRI, the INC
      provided new diagnostic information in 5 (83.3%) cases, in neonates studied after
      birth by ultrasound in 32 (82%). Magnetic resonance imaging in the INC did not
      entail additional knowledge in 9 (18.7%) cases. CONCLUSIONS: The INC enables MRI
      in preterm newborns and those with low/extremely low body weight. These studies
      are necessary to assess the extent of changes in the central nervous system and
      other organs. Incubator coils, designed specifically for neonates, allow more
      accurate diagnosis than previously used coils for adults. MRI results allow one
      to determine prognosis, for more accurate planning of diagnostics, helping to
      make appropriate therapeutic decisions.

PMID- 27695499
TI  - Comparative investigation of antioxidant activity of human serum blood by
      amperometric, voltammetric and chemiluminescent methods.
AB  - INTRODUCTION: A blood test can provide important information about the functional
      state of the antioxidant system. Malfunction of this system increases the
      concentration of free radicals and can cause oxidative stress. A difficulty in
      assessing oxidative stress is the lack of a universal method for determining the
      antioxidant activity (AOA) of blood components, because of their different
      nature. MATERIAL AND METHODS: The objects of investigation were sera of 30 male
      patients with a diagnosis of alcohol dependence syndrome and healthy donors.
      Comparative investigation of total antioxidant activity (TAA) of human serum
      blood was carried out by voltammetric (VA), amperometric (AM) and
      chemiluminescent (HL) methods. RESULTS: All applied methods revealed that serum
      TAA of the patients with alcoholism is lower than TAA of healthy donors (control
      group); according to amperometric method the average value of serum TAA was 850
      +/-210 nA * s, and 660 +/-150 nA * s for healthy donors and alcoholics
      respectively (p < 0.05). Similar trend was revealed by chemiluminescence and
      voltammetry methods. The results confirm that thiol compounds make a significant
      contribution to the antioxidant activity of serum. The average thiol
      concentrations were 0.94 +/-0.34 mmol/l and 1.21 +/-0.36 mmol/l (p < 0.05) for
      alcoholics and healthy donors respectively. Decreasing thiol concentration in
      blood of alcoholics leads to depletion of antioxidant systems of blood. However,
      the differences between the results of AM, VA and HL methods were significant,
      because they reflected different aspects of antioxidant activity. CONCLUSIONS:
      For objective assessment of antioxidant activity of biological objects, we
      suggest using methods based on different model systems.

PMID- 27695500
TI  - Obstructive sleep apnea predicts risk of metabolic syndrome independently of
      obesity: a meta-analysis.
AB  - INTRODUCTION: Obstructive sleep apnea (OSA) has been suggested to be associated
      with a high risk of metabolic syndrome (MS). However, results on whether the
      association between OSA and risk of MS is independent of obesity, and the effect
      of nocturnal intermittent hypoxia (IH) on MS, are conflicting. Our purpose was to
      estimate the magnitude of the independent association between OSA and risk of MS
      and further explore whether nocturnal IH in OSA plays a role in MS risk. MATERIAL
      AND METHODS: The PubMed and EMBASE databases were systematically searched (until
      January 21, 2015) for available observational evidence. Unadjusted and body mass
      index (BMI)-adjusted pooled odds ratios (ORs) for MS in OSA or higher nocturnal
      IH were calculated using fixed or random models. Tests of homogeneity,
      publication bias, and robustness of the results were performed. RESULTS: A total
      of 13 independent studies (involving 857 participants in 3 case-control studies
      and 7077 participants in 10 cross-sectional studies) were included. The OSA was
      significantly associated with an increased risk of MS in a meta-analysis of 10
      studies (pooled OR = 1.72, 95% CI: 1.31-2.26, p < 0.001), with a BMI-adjusted
      pooled OR of 1.97 (95% CI: 1.34-2.88, p < 0.001). Pooled results from 3 studies
      on the oxygen desaturation index (ODI) and MS risk (OR = 1.96, 95% CI: 1.73-2.22,
      p < 0.001) and 3 studies on the cumulative percentage of sleep time with SpO2
      below 90% (CT90) and MS risk (OR = 1.05, 95% CI: 1.02-1.07, p < 0.001) were also
      significant. CONCLUSIONS: Our findings demonstrated a significant association
      between OSA and increased MS risk independent of BMI, and further indicated a
      role of nocturnal IH in this association.

PMID- 27695501
TI  - Effectiveness and safety of vedolizumab for treatment of Crohn's disease: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: The aim of this systematic review (SR) and meta-analysis was to
      assess the efficacy and safety of vedolizumab in the treatment of Crohn's disease
      (CD). MATERIAL AND METHODS: A systematic literature search was conducted in
      Medline/PubMed, Embase and Cochrane Library until 25 January, 2015. Included
      studies were critically appraised according to the PRISMA protocol. Assessment in
      specified subgroups of CD patients and meta-analysis with Revman software were
      performed. RESULTS: Two randomized controlled trial (RCTs) were included in a
      meta-analysis for the induction phase of therapy: GEMINI II and GEMINI III. The
      clinical response was significantly higher for patients who received vedolizumab
      compared to placebo in the general population (risk benefit (RB) = 1.48; p =
      0.0006) and in both analyzed subgroups: patients with previous failure of anti
      TNFs treatment (RB = 1.51; p = 0.006) and patients naive to earlier anti-TNFs (RB
      = 1.41; p = 0.001). The clinical remission in the general population and
      subpopulation of TNF-antagonist naive patients was significantly higher for
      patients who received vedolizumab compared to placebo (RB = 1.77; p = 0.003; RB =
      2.29; p = 0.0004; respectively). Meta-analysis for adverse events, serious
      adverse events (SAEs) and serious infections, revealed that vedolizumab was as
      safe as placebo in the induction phase of therapy. CONCLUSIONS: The clinical
      response was significantly higher for patients who received vedolizumab in the
      general population and in both analyzed subgroups of patients. The clinical
      remission in the general population and subpopulation of TNF-antagonist naive
      patients was significantly higher for vedolizumab, but no significant differences
      were revealed in the subgroup of patients with previous TNF antagonist failure.

PMID- 27695502
TI  - An indirect comparison of infliximab versus adalimumab or golimumab for active
      ulcerative colitis.
AB  - INTRODUCTION: The aim of the study was to compare adalimumab or golimumab with
      infliximab in patients with moderately-to-severely active ulcerative colitis
      (UC). MATERIAL AND METHODS: This paper was prepared according to the PRISMA
      guidelines. The systematic literature search was performed in PubMed, Embase, and
      Cochrane Library. No direct head-to-head comparisons for infliximab vs.
      adalimumab or golimumab were available so an indirect comparison according to the
      Bucher method was performed after a homogeneity evaluation of the included
      studies. RESULTS: Six RCTs were included in the systematic review. An indirect
      comparison was performed, which revealed that infliximab was more effective in
      inducing clinical response compared with both doses of adalimumab (160/80 mg or
      80/40 mg; p < 0.05), and, in clinical remission, infliximab was more effective
      than adalimumab (only for a dosage regime of 80/40 mg; p < 0.05). No
      statistically significant differences in clinical response and clinical remission
      were observed between infliximab and golimumab in the induction phase. A
      significant (p < 0.05) advantage only of infliximab compared with adalimumab at
      doses of 80/40 mg and 80/160 mg was seen in terms of clinical response in the
      maintenance phase (up to 52-54 weeks). The indirect comparison revealed that
      serious adverse events were significantly more frequent among patients treated
      with a maintenance dose of 100 mg of golimumab compared with those treated with
      infliximab (p < 0.05). CONCLUSIONS: No significant differences in efficacy in the
      maintenance phase between infliximab and golimumab or adalimumab were revealed.
      Infliximab proved to be more effective than adalimumab but of similar efficacy to
      that of golimumab in the induction phase.

PMID- 27695503
TI  - Prognostic significance of cyclooxygenase-2 expression in patients with
      hepatocellular carcinoma: a meta-analysis.
AB  - INTRODUCTION: Cyclooxygenase-2 (COX-2) is believed to be an important enzyme in
      the carcinogenesis of hepatocellular carcinoma (HCC). However, it is still
      controversial whether COX-2 expression can be regarded as a prognostic factor for
      HCC patients. We performed a systematic review and meta-analysis of studies
      assessing the clinical and prognostic significance of COX-2 expression in HCC.
      MATERIAL AND METHODS: Identification and review of publications assessing
      clinical or prognostic significance of COX-2 expression in HCC until November 1,
      2014. A meta-analysis was performed to clarify the association between COX-2
      expression and clinical outcomes. RESULTS: A total of 11 publications met the
      criteria and included 943 cases. Analysis of these data showed that COX-2
      expression was not significantly correlated with capsular formation (OR = 0.84,
      95% confidence interval (CI): 0.46-1.55, p = 0.58), tumor TNM stage (OR = 0.73,
      95% CI: 0.23-2.33, p = 0.59), vascular invasion (OR = 1.04, 95% CI: 0.25-4.35, p
      = 0.96), tumor size (OR = 0.78, 95% CI: 0.21-2.86, p = 0.71), or tumor
      differentiation degree (OR = 1.08, 95% CI: 0.42-2.79, p = 0.87). However, in the
      identified studies, COX-2 expression was strongly associated with high alpha
      fetoprotein level (OR = 1.83, 95% CI: 1.01-3.33, p = 0.05), HBsAg status (OR =
      1.85, 95% CI: 1.13-3.03, p = 0.01), decreased overall survival (relative risk
      (RR): 1.54, 95% CI: 1.18-2.02, p = 0.001) and decreased disease-free survival (RR
      = 1.49, 95% CI: 1.22-1.81, p < 0.001). CONCLUSIONS: This meta-analysis shows that
      COX-2 expression in HCC is associated with decreased overall and disease-free
      survival and thus marks a worse prognosis. Nevertheless, more large sample and
      well-designed studies are warranted to confirm this finding.

PMID- 27695504
TI  - Vitamin D receptor gene FokI polymorphisms and tuberculosis susceptibility: a
      meta-analysis.
AB  - INTRODUCTION: The association between FokI polymorphism of vitamin D receptor
      (VDR) and tuberculosis (TB) susceptibility has been investigated previously;
      however, the results were inconsistent and conflicting. In the present study, a
      meta-analysis was performed to assess the relationship between VDR FokI gene
      polymorphism and the risk of TB. MATERIAL AND METHODS: Databases including PubMed
      and Embase were searched for genetic association studies of FokI polymorphism of
      vitamin D receptor (VDR) and TB. Data were extracted by two independent authors
      and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated
      to assess the strength of the association between VDR FokI gene polymorphism and
      TB risk. Meta-regression and subgroup analyses were performed to identify the
      source of heterogeneity. RESULTS: Thirty-four studies with a total of 5669 cases
      and 6525 controls were reviewed in the present meta-analysis. A statistically
      significant correlation was found between VDR FokI gene polymorphism and
      increased TB risk in two comparison models: the homozygote model (ff vs. FF: OR =
      1.37, 95% CI: 1.17-1.60; Pheterogeneity = 0.001) and the recessive model (ff vs.
      Ff + FF: OR = 1.32, 95% CI: 1.14-1.52; Pheterogeneity = 0.006). Meta-regression
      found no source contributing to heterogeneity. However, sub-group analyses
      revealed that there was a statistically increased TB risk in the East and
      Southeast Asian population. CONCLUSIONS: Synthesis of the available studies
      suggests that homozygosity for the FokI polymorphism of the VDR gene might be
      associated with an increased TB risk, especially in the East and Southeast Asian
      population. Additional well-designed, larger-scale epidemiological studies among
      different ethnicities are needed.

PMID- 27695505
TI  - History and current use of mild therapeutic hypothermia after cardiac arrest.
AB  - In spite of many years of development and implementation of pre-hospital advanced
      life support programmes, the survival rate of out-of-hospital cardiac arrest
      (OHCA) used to be very poor. Neurologic injury from cerebral hypoxia is the most
      common cause of death in patients with OHCA. In the past two decades, post
      resuscitation care has developed many new concepts aimed at improving the
      neurological outcome and survival rate of patients after cardiac arrest.
      Systematic post-cardiac arrest care after the return of spontaneous circulation,
      including induced mild therapeutic hypothermia (TH) in selected patients, is
      aimed at significantly improving rates of long-term neurologically intact
      survival. This review summarises the history and current knowledge in the field
      of mild TH after OHCA.

PMID- 27695508
TI  - Reversal agents of non-vitamin K dependent anticoagulants: a rapid review of the
      changing horizon.
AB  - The newer non-vitamin K dependent anticoagulants (NOACs) have provided a new tool
      in the armamentarium of physicians treating nonvalvular atrial fibrillation and
      thromboembolism. Slowly, but steadily, there has been an increased preference of
      NOACs over vitamin K antagonists. However, the major limiting factor and the
      concern that precluded their use was lack of reversal in emergent situations.
      With the advent of reversal agents such as idarucizumab, andexanet alfa and
      PER977, this gap is also being filled. This will further increase the spectrum of
      usage of NOACs. In this review we present the detailed information on the
      completed trials on the reversal agents, the ongoinng trials, and their site of
      action. The reversal agent idarucizumab is FDA approved and readily available.
      The others are in clinical trials and are soon expected to be available in
      clinical practice.

PMID- 27695509
TI  - Subcutaneous implantable cardioverter-defibrillator (S-ICD) for secondary
      prevention of sudden cardiac death.

PMID- 27695506
TI  - Diabetic macular edema, retinopathy and age-related macular degeneration as
      inflammatory conditions.
AB  - Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications
      affecting about 25% of all patients with long-standing type 1 and type 2 diabetes
      mellitus and are a major cause of significant decrease in vision and quality of
      life. Age-related macular degeneration (AMD) is not uncommon, and diabetes
      mellitus affects the incidence and progression of AMD through altering
      hemodynamics, increasing oxidative stress, accumulating advanced glycation end
      products, etc. Recent studies suggest that DME, DR and AMD are inflammatory
      conditions characterized by a breakdown of the blood-retinal barrier,
      inflammatory processes and an increase in vascular permeability. Key factors that
      seem to have a dominant role in DME, DR and AMD are angiotensin II,
      prostaglandins and the vascular endothelial growth factor and a deficiency of
      anti-inflammatory bioactive lipids. The imbalance between pro- and anti
      inflammatory eicosanoids and enhanced production of pro-angiogenic factors may
      initiate the onset and progression of DME, DR and AMD. This implies that
      bioactive lipids that possess anti-inflammatory actions and suppress the
      production of angiogenic factors could be employed in the prevention and
      management of DME, DR and AMD.

PMID- 27695510
TI  - Closing the gap in HIV prevention and care for children: early insights from a
      model that links communities and health care facilities in Uganda.
AB  - Inequities in access to HIV prevention and treatment for children remain a global
      challenge and a black spot to effective HIV prevention and response especially in
      many HIV endemic countries like Uganda. In Uganda while about 51% of the adults
      living with HIV are on antiretrovirals, only 39% of the children aged 0-14 years
      accessed the needed HIV care in 2014. In this article, it is argued that much
      focus on health system interventions with little regard to bridging the gap
      between health facilities, where much of the care is provided, and the
      communities, where children are conceived, born and cared for, contributes to and
      sustains this inequality. Investments need to be made in building and
      implementing models that create and enhance linkages between communities and
      health care facilities. Success factors from the Towards an AIDS Free Generation
      in Uganda project model in creating these linkages are bringing all actors
      together in one approach, building on existing community structures and enabling
      community health workers to be the linking pin between communities and
      facilities. Only with models like this, full elimination of mother-to-child
      transmission and paediatric HIV care coverage (0-14 years) can be reached in
      Uganda and other HIV endemic countries.

PMID- 27695511
TI  - A grounded theory of positive youth development through sport based on results
      from a qualitative meta-study.
AB  - The overall purpose of this study was to create a model of positive youth
      development (PYD) through sport grounded in the extant qualitative literature.
      More specifically, the first objective was to review and evaluate qualitative
      studies of PYD in sport. The second objective was to analyze and synthesize
      findings from these studies. Following record identification and screening, 63
      articles were retained for analysis. Meta-method analysis revealed strengths of
      studies were the use of multiple data collection and validity techniques, which
      produced high-quality data. Weaknesses were limited use of 'named' methodologies
      and inadequate reporting of sampling procedures. Philosophical perspectives were
      rarely reported, and theory was used sparingly. Results of an inductive meta-data
      analysis produced three categories: PYD climate (adult relationships, peer
      relationships, and parental involvement), life skills program focus (life skill
      building activities and transfer activities), and PYD outcomes (in personal,
      social, and physical domains). A model that distinguishes between implicit and
      explicit processes to PYD is presented.

PMID- 27695507
TI  - Novel surgical techniques, regenerative medicine, tissue engineering and
      innovative immunosuppression in kidney transplantation.
AB  - On the 60th anniversary of the first successfully performed renal
      transplantation, we summarize the historical, current and potential future status
      of kidney transplantation. We discuss three different aspects with a potential
      significant influence on kidney transplantation progress: the development of
      surgical techniques, the influence of regenerative medicine and tissue
      engineering, and changes in immunosuppression. We evaluate the standard open
      surgical procedures with modern techniques and compare them to less invasive
      videoscopic as well as robotic techniques. The role of tissue engineering and
      regenerative medicine as a potential method for future kidney regeneration or
      replacement and the interesting search for novel solutions in the field of
      immunosuppression will be discussed. After 60 years since the first successfully
      performed kidney transplantation, we can conclude that the greatest achievements
      are associated with the development of surgical techniques and with planned
      systemic immunosuppression.

PMID- 27695512
TI  - Detecting Spatio-Temporal Modes in Multivariate Data by Entropy Field
      Decomposition.
AB  - A new data analysis method that addresses a general problem of detecting spatio
      temporal variations in multivariate data is presented. The method utilizes two
      recent and complimentary general approaches to data analysis, information field
      theory (IFT) and entropy spectrum pathways (ESP). Both methods reformulate and
      incorporate Bayesian theory, thus use prior information to uncover underlying
      structure of the unknown signal. Unification of ESP and IFT creates an approach
      that is non-Gaussian and non-linear by construction and is found to produce
      unique spatio-temporal modes of signal behavior that can be ranked according to
      their significance, from which space-time trajectories of parameter variations
      can be constructed and quantified. Two brief examples of real world applications
      of the theory to the analysis of data bearing completely different, unrelated
      nature, lacking any underlying similarity, are also presented. The first example
      provides an analysis of resting state functional magnetic resonance imaging
      (rsFMRI) data that allowed us to create an efficient and accurate computational
      method for assessing and categorizing brain activity. The second example
      demonstrates the potential of the method in the application to the analysis of a
      strong atmospheric storm circulation system during the complicated stage of
      tornado development and formation using data recorded by a mobile Doppler radar.
      Reference implementation of the method will be made available as a part of the
      QUEST toolkit that is currently under development at the Center for Scientific
      Computation in Imaging.

PMID- 27695513
TI  - Will life find a way? Evolution of marine species under global change.
AB  - Projections of marine biodiversity and implementation of effective actions for
      its maintenance in the face of current rapid global environmental change are
      constrained by our limited understanding of species' adaptive responses,
      including transgenerational plasticity, epigenetics and natural selection. This
      special issue presents 13 novel studies, which employ experimental and modelling
      approaches to (i) investigate plastic and evolutionary responses of marine
      species to major global change drivers; (ii) ask relevant broad eco-evolutionary
      questions, implementing multiple species and populations studies; (iii) show the
      advantages of using advanced experimental designs and tools; (iv) construct novel
      model organisms for marine evolution; (v) help identifying future challenges for
      the field; and (vi) highlight the importance of incorporating existing
      evolutionary theory into management solutions for the marine realm. What emerges
      is that at least some populations of marine species have the ability to adapt to
      future global change conditions. However, marine organisms' capacity for
      adaptation appears finite, due to evolutionary trade-offs and possible rapid
      losses in genetic diversity. This further corroborates the idea that acquiring an
      evolutionary perspective on how marine life will respond to the selective
      pressure of future global changes will guide us in better identifying which
      conservation efforts will be most needed and most effective.

PMID- 27695514
TI  - Physiological plasticity and local adaptation to elevated pCO2 in calcareous
      algae: an ontogenetic and geographic approach.
AB  - To project how ocean acidification will impact biological communities in the
      future, it is critical to understand the potential for local adaptation and the
      physiological plasticity of marine organisms throughout their entire life cycle,
      as some stages may be more vulnerable than others. Coralline algae are ecosystem
      engineers that play significant functional roles in oceans worldwide and are
      considered vulnerable to ocean acidification. Using different stages of coralline
      algae, we tested the hypothesis that populations living in environments with
      higher environmental variability and exposed to higher levels of pCO 2 would be
      less affected by high pCO 2 than populations from a more stable environment
      experiencing lower levels of pCO 2. Our results show that spores are less
      sensitive to elevated pCO 2 than adults. Spore growth and mortality were not
      affected by pCO 2 level; however, elevated pCO 2 negatively impacted the
      physiology and growth rates of adults, with stronger effects in populations that
      experienced both lower levels of pCO 2 and lower variability in carbonate
      chemistry, suggesting local adaptation. Differences in physiological plasticity
      and the potential for adaptation could have important implications for the
      ecological and evolutionary responses of coralline algae to future environmental
      changes.

PMID- 27695515
TI  - An in situ assessment of local adaptation in a calcifying polychaete from a
      shallow CO2 vent system.
AB  - Ocean acidification (OA) is likely to exert selective pressure on natural
      populations. Our ability to predict which marine species will adapt to OA and
      what underlies this adaptive potential is of high conservation and resource
      management priority. Using a naturally low-pH vent site in the Mediterranean Sea
      (Castello Aragonese, Ischia) mirroring projected future OA conditions, we carried
      out a reciprocal transplant experiment to investigate the relative importance of
      phenotypic plasticity and local adaptation in two populations of the sessile,
      calcifying polychaete Simplaria sp. (Annelida, Serpulidae, Spirorbinae): one
      residing in low pH and the other from a nearby ambient (i.e. high) pH site. We
      measured a suite of fitness-related traits (i.e. survival, reproductive output,
      maturation, population growth) and tube growth rates in laboratory-bred F2
      generation individuals from both populations reciprocally transplanted back into
      both ambient and low-pH in situ habitats. Both populations showed lower
      expression in all traits, but increased tube growth rates, when exposed to low-pH
      compared with high-pH conditions, regardless of their site of origin suggesting
      that local adaptation to low-pH conditions has not occurred. We also found
      comparable levels of plasticity in the two populations investigated, suggesting
      no influence of long-term exposure to low pH on the ability of populations to
      adjust their phenotype. Despite high variation in trait values among sites and
      the relatively extreme conditions at the low pH site (pH < 7.36), response trends
      were consistent across traits. Hence, our data suggest that, for Simplaria and
      possibly other calcifiers, neither local adaptations nor sufficient phenotypic
      plasticity levels appear to suffice in order to compensate for the negative
      impacts of OA on long-term survival. Our work also emphasizes the utility of
      field experiments in natural environments subjected to high level of pCO 2 for
      elucidating the potential for adaptation to future scenarios of OA.

PMID- 27695516
TI  - Transgenerational plasticity of reproduction depends on rate of warming across
      generations.
AB  - Predicting the impacts of climate change to biological systems requires an
      understanding of the ability for species to acclimate to the projected
      environmental change through phenotypic plasticity. Determining the effects of
      higher temperatures on individual performance is made more complex by the
      potential for environmental conditions experienced in previous and current
      generations to independently affect phenotypic responses to high temperatures. We
      used a model coral reef fish (Acanthochromis polyacanthus) to investigate the
      influence of thermal conditions experienced by two generations on reproductive
      output and the quality of offspring produced by adults. We found that more
      gradual warming over two generations, +1.5 degrees C in the first generation and
      then +3.0 degrees C in the second generation, resulted in greater plasticity of
      reproductive attributes, compared to fish that experienced the same increase in
      one generation. Reproduction ceased at the projected future summer temperature
      (31.5 degrees C) when fish experienced +3.0 degrees C for two generations.
      Additionally, we found that transgenerational plasticity to +1.5 degrees C
      induced full restoration of thermally affected reproductive and offspring
      attributes, which was not possible with developmental plasticity alone. Our
      results suggest that transgenerational effects differ depending on the absolute
      thermal change and in which life stage the thermal change is experienced.

PMID- 27695517
TI  - Multi-generational responses of a marine polychaete to a rapid change in seawater
      pCO2.
AB  - Little is known of the capacity that marine metazoans have to evolve under rapid
      p CO 2 changes. Consequently, we reared a marine polychaete, Ophryotrocha
      labronica, previously cultured for approximately 33 generations under a
      low/variable pH regime, under elevated and low p CO 2 for six generations. The
      strain used was found to be tolerant to elevated p CO 2 conditions. In
      generations F1 and F2 females' fecundity was significantly lower in the low p CO
      2 treatment. However, from generation F3 onwards there were no differences
      between p CO 2 treatments, indicating that trans-generational effects enabled the
      restoration and maintenance of reproductive output. Whilst the initial fitness
      recovery was likely driven by trans-generational plasticity (TGP), the results
      from reciprocal transplant assays, performed using F7 individuals, made it
      difficult to disentangle between whether TGP had persisted across multiple
      generations, or if evolutionary adaptation had occurred. Nonetheless, both are
      important mechanisms for persistence under climate change. Overall, our study
      highlights the importance of multi-generational experiments in more accurately
      determining marine metazoans' responses to changes in p CO 2, and strengthens the
      case for exploring their use in conservation, by creating specific p CO 2
      tolerant strains of keystone ecosystem species.

PMID- 27695518
TI  - Transgenerational effects persist down the maternal line in marine sticklebacks:
      gene expression matches physiology in a warming ocean.
AB  - Transgenerational effects can buffer populations against environmental change,
      yet little is known about underlying mechanisms, their persistence or the
      influence of environmental cue timing. We investigated mitochondrial respiratory
      capacity (MRC) and gene expression of marine sticklebacks that experienced acute
      or developmental acclimation to simulated ocean warming (21 degrees C) across
      three generations. Previous work showed that acute acclimation of grandmothers to
      21 degrees C led to lower (optimized) offspring MRCs. Here, developmental
      acclimation of mothers to 21 degrees C led to higher, but more efficient
      offspring MRCs. Offspring with a 21 degrees C * 17 degrees C grandmother-mother
      environment mismatch showed metabolic compensation: their MRCs were as low as
      offspring with a 17 degrees C thermal history across generations. Transcriptional
      analyses showed primarily maternal but also grandmaternal environment effects:
      genes involved in metabolism and mitochondrial protein biosynthesis were
      differentially expressed when mothers developed at 21 degrees C, whereas 21
      degrees C grandmothers influenced genes involved in hemostasis and apoptosis.
      Genes involved in mitochondrial respiration all showed higher expression when
      mothers developed at 21 degrees  and lower expression in the 21 degrees C * 17
      degrees C group, matching the phenotypic pattern for MRCs. Our study links
      transcriptomics to physiology under climate change, and demonstrates that
      mechanisms underlying transgenerational effects persist across multiple
      generations with specific outcomes depending on acclimation type and
      environmental mismatch between generations.

PMID- 27695520
TI  - Loss of genetic diversity as a consequence of selection in response to high pCO2.
AB  - Standing genetic variation may allow for rapid evolutionary response to the
      geologically unprecedented changes in global conditions. However, there is little
      known about the consequences of such rapid evolutionary change. Here, we measure
      genetic responses to experimental low and high pCO 2 levels in purple sea urchin
      larvae, Strongylocentrotus purpuratus. We found greater loss of nucleotide
      diversity in high pCO 2 levels (18.61%; 900 MUatm) compared to low pCO 2 levels
      (10.12%; 400 MUatm). In the wild, this loss could limit the evolutionary capacity
      of future generations. In contrast, we found minimal evidence that purple sea
      urchin larvae physiologically respond to high pCO 2 through alternative splicing
      of transcripts (11 genes), despite a strong signal of alternative splicing
      between different developmental stages (1193 genes). However, in response to high
      pCO 2, four of the 11 alternatively spliced transcripts encoded ribosomal
      proteins, suggesting the regulation of translation as a potential response
      mechanism. The results of this study indicate that while the purple urchin
      presently may have enough standing genetic variation in response to rapid
      environmental change, this reservoir of resilience is a finite resource and could
      quickly diminish.

PMID- 27695519
TI  - Selection on oxidative phosphorylation and ribosomal structure as a
      multigenerational response to ocean acidification in the common copepod
      Pseudocalanus acuspes.
AB  - Ocean acidification is expected to have dramatic impacts on oceanic ecosystems,
      yet surprisingly few studies currently examine long-term adaptive and plastic
      responses of marine invertebrates to pCO 2 stress. Here, we exposed populations
      of the common copepod Pseudocalanus acuspes to three pCO 2 regimes (400, 900, and
      1550 MUatm) for two generations, after which we conducted a reciprocal transplant
      experiment. A de novo transcriptome was assembled, annotated, and gene expression
      data revealed that genes involved in RNA transcription were strongly down
      regulated in populations with long-term exposure to a high pCO 2 environment,
      even after transplantation back to control levels. In addition, 747 000 SNPs were
      identified, out of which 1513 showed consistent changes in nucleotide frequency
      between replicates of control and high pCO 2 populations. Functions involving RNA
      transcription and ribosomal function, as well as ion transport and oxidative
      phosphorylation, were highly overrepresented. We thus conclude that pCO 2 stress
      appears to impose selection in copepods on RNA synthesis and translation,
      possibly modulated by helicase expression. Using a physiological hypothesis
      testing strategy to mine gene expression data, we herein increase the power to
      detect cellular targets of ocean acidification. This novel approach seems
      promising for future studies of effects of environmental changes in ecologically
      important nonmodel organisms.

PMID- 27695521
TI  - Can trans-generational experiments be used to enhance species resilience to ocean
      warming and acidification?
AB  - Human-assisted, trans-generational exposure to ocean warming and acidification
      has been proposed as a conservation and/or restoration tool to produce resilient
      offspring. To improve our understanding of the need for and the efficacy of this
      approach, we characterized life-history and physiological responses in offspring
      of the marine polychaete Ophryotrocha labronica exposed to predicted ocean
      warming (OW: + 3 degrees C), ocean acidification (OA: pH -0.5) and their
      combination (OWA: + 3 degrees C, pH -0.5), following the exposure of their
      parents to either control conditions (within-generational exposure) or the same
      conditions (trans-generational exposure). Trans-generational exposure to OW fully
      alleviated the negative effects of within-generational exposure to OW on
      fecundity and egg volume and was accompanied by increased metabolic activity.
      While within-generational exposure to OA reduced juvenile growth rates and egg
      volume, trans-generational exposure alleviated the former but could not restore
      the latter. Surprisingly, exposure to OWA had no negative impacts within- or
      trans-generationally. Our results highlight the potential for trans-generational
      laboratory experiments in producing offspring that are resilient to OW and OA.
      However, trans-generational exposure does not always appear to improve traits and
      therefore may not be a universally useful tool for all species in the face of
      global change.

PMID- 27695522
TI  - Adaptation to climate change: trade-offs among responses to multiple stressors in
      an intertidal crustacean.
AB  - Trade-offs may influence both physiological and evolutionary responses to co
      occurring stressors, but their effects on both plastic and adaptive responses to
      climate change are poorly understood. To test for genetic and physiological trade
      offs incurred in tolerating multiple stressors, we hybridized two populations of
      the intertidal copepod Tigriopus californicus that were divergent for both heat
      and salinity tolerance. Starting in the F2 generation, we selected for increased
      tolerance of heat, low salinity, and high salinity in replicate lines. After five
      generations of selection, heat-selected lines had greater heat tolerance but
      lower fecundity, indicating an energetic cost to tolerance. Lines selected for
      increased salinity tolerance did not show evidence of adaptation to their
      respective environments; however, hypo-osmotic selection lines showed substantial
      loss of tolerance to hyperosmotic stress. Neither of the salinity selection
      regimes resulted in diminished heat tolerance at ambient salinity; however,
      simultaneous exposure to heat and hypo-osmotic stress led to decreased heat
      tolerance, implying a physiological trade-off in tolerance to the two stressors.
      When we quantified the transcriptomic response to heat and salinity stress via
      RNA sequencing, we observed little overlap in the stress responses, suggesting
      the observed synergistic effects of heat and salinity stress were driven by
      competing energetic demands, rather than shared stress response pathways.

PMID- 27695523
TI  - Swift thermal reaction norm evolution in a key marine phytoplankton species.
AB  - Temperature has a profound effect on the species composition and physiology of
      marine phytoplankton, a polyphyletic group of microbes responsible for half of
      global primary production. Here, we ask whether and how thermal reaction norms in
      a key calcifying species, the coccolithophore Emiliania huxleyi, change as a
      result of 2.5 years of experimental evolution to a temperature ~2 degrees C below
      its upper thermal limit. Replicate experimental populations derived from a single
      genotype isolated from Norwegian coastal waters were grown at two temperatures
      for 2.5 years before assessing thermal responses at 6 temperatures ranging from
      15 to 26 degrees C, with pCO 2 (400/1100/2200 MUatm) as a fully factorial
      additional factor. The two selection temperatures (15 degrees /26.3 degrees C)
      led to a marked divergence of thermal reaction norms. Optimal growth temperatures
      were 0.7 degrees C higher in experimental populations selected at 26.3 degrees C
      than those selected at 15.0 degrees C. An additional negative effect of high pCO
      2 on maximal growth rate (8% decrease relative to lowest level) was observed.
      Finally, the maximum persistence temperature (Tmax) differed by 1-3 degrees C
      between experimental treatments, as a result of an interaction between pCO 2 and
      the temperature selection. Taken together, we demonstrate that several attributes
      of thermal reaction norms in phytoplankton may change faster than the predicted
      progression of ocean warming.

PMID- 27695524
TI  - Ocean acidification influences host DNA methylation and phenotypic plasticity in
      environmentally susceptible corals.
AB  - As climate change challenges organismal fitness by creating a phenotype
      environment mismatch, phenotypic plasticity generated by epigenetic mechanisms
      (e.g., DNA methylation) can provide a temporal buffer for genetic adaptation.
      Epigenetic mechanisms may be crucial for sessile benthic marine organisms, such
      as reef-building corals, where ocean acidification (OA) and warming reflect in
      strong negative responses. We tested the potential for scleractinian corals to
      exhibit phenotypic plasticity associated with a change in DNA methylation in
      response to OA. Clonal coral fragments of the environmentally sensitive
      Pocillopora damicornis and more environmentally robust Montipora capitata were
      exposed to fluctuating ambient pH (7.9-7.65) and low pH (7.6-7.35) conditions in
      common garden tanks for ~6 weeks. M. capitata responded weakly, or acclimated
      more quickly, to OA, with no difference in calcification, minimal separation of
      metabolomic profiles, and no change in DNA methylation between treatments.
      Conversely, P. damicornis exhibited diminished calcification at low pH, stronger
      separation in metabolomic profiles, and responsiveness of DNA methylation to
      treatment. Our data suggest corals differ in their temporal dynamics and
      sensitivity for environmentally triggered real-time epigenetic reprogramming. The
      generation of potentially heritable plasticity via environmental induction of DNA
      methylation provides an avenue for assisted evolution applications in corals
      under rapid climate change.

PMID- 27695525
TI  - Growth rate evolution in improved environments under Prodigal Son dynamics.
AB  - I use an individual-based model to investigate the evolution of cell division
      rates in asexual populations under chronic environmental enrichment. I show that
      maintaining increased growth rates over hundreds of generations following
      environmental improvement can be limited by increases in cellular damage
      associated with more rapid reproduction. In the absence of further evolution to
      either increase damage tolerance or decrease the cost of repair or rate of
      damage, environmental improvement does not reliably lead to long-term increases
      in reproductive rate in microbes. Here, more rapid cell division rates also
      increases damage, leading to selection for damage avoidance or repair, and a
      subsequent decrease in population growth, which I call Prodigal Son dynamics,
      because the consequences of 'living fast' force a return to ancestral growth
      rates. Understanding the conditions under which environmental enrichment is
      expected to sustainably increase cell division rates is important in applications
      that require rapid cell division (e.g. biofuel reactors) or seek to avoid the
      emergence of rapid cell division rates (controlling biofouling).

PMID- 27695526
TI  - Global change, life-history complexity and the potential for evolutionary rescue.
AB  - Most organisms have complex life cycles, and in marine taxa, larval life-history
      stages tend to be more sensitive to environmental stress than adult
      (reproductive) life-history stages. While there are several models of stage
      specific adaptation across the life history, the extent to which differential
      sensitivity to environmental stress (defined here as reductions in absolute
      fitness across the life history) affects the tempo of adaptive evolution to
      change remains unclear. We used a heuristic model to explore how commonly
      observed features associated with marine complex life histories alter a
      population's capacity to cope with environmental change. We found that increasing
      the complexity of the life history generally reduces the evolutionary potential
      of taxa to cope with environmental change. Our model also predicted that genetic
      correlations in stress tolerance between stages, levels of genetic variance in
      each stage, and the relative plasticity of different stages, all interact to
      affect the maximum rate of environmental change that will permit species
      persistence. Our results suggest that marine organisms with complex life cycles
      are particularly vulnerable to anthropogenic global change, but we lack empirical
      estimates of key parameters for most species.

PMID- 27695527
TI  - Dikir Farmasi: folk songs for health education.
AB  - In an effort to enhance public awareness, we develop Dikir Farmasi as an
      innovative approach to deliver health information. Dikir Farmasi combines the
      elements of dikir barat (a type of traditional folk song rhythm) and traditional
      sketches which are popular in the state of Kelantan, Malaysia. These sketches and
      dikir barat rhythmic songs, with lyrics touch on issues such as drug abuse and
      regulation are presented in an entertaining and humorous way. Health promotion
      messages are disseminated using Dikir Farmasi in the form of compact disks, video
      compact disks, stage performance, exhibition, social media, printed media
      (signboard, brochure and flyer).

PMID- 27695528
TI  - Management of equivocal (early) Fournier's gangrene.
AB  - BACKGROUND: Fournier's gangrene (FG) is an acute progressive necrotizing
      fasciitis of the genital area and perineum with possible extension to the
      abdominal wall. Surgical debridement is the gold standard management modality of
      established patients. Equivocal (early) FG represents a challenge in diagnosis.
      The objective of this study was to compare conservative management and early
      exploration in cases of equivocal (early) FG. METHODS: This was an observational
      study where data of all patients diagnosed as early FG in our departments over 4
      years (2011-2015) were enrolled. Patients were divided into two groups: group 1
      with conservative treatment, and group 2 managed with urgent exploration with
      longitudinal hemiscrotal incision starting from external inguinal ring. All
      patients' demographics, vital signs, laboratory finding and clinical findings
      were reported. RESULTS: A total of 28 patients were enrolled in the study. Group
      1 was managed with conservative treatment (17 patients) and group 2 underwent
      urgent exploration (11 patients). Overall, four patients (23.5%) out of 17
      patients of group 1 showed a good response to conservative management without any
      surgical debridement. A total of 13 patients (76.5%) developed gangrenous
      discoloration and needed surgical debridement later. In group 2, four patients
      (36.4%) underwent scrotal exploration and release incision only without
      debridement and showed an excellent clinical outcome. A total of four patients
      (36.4%) underwent debridement with excision of doubtful deep subcutaneous and
      fascial tissues. The remaining three patients (27.2%) underwent debridement of
      necrotic fascia. The hospital stay was significantly shorter in group 2 patients
      than group 1 (7.5 +/- 3.75 versus 13.4 +/- 5.19 days p < 0.05). The mean number
      of debridement sessions was 3.74 +/- 0.69 in group 1 versus 1.82 +/- 0.34 in
      group 2. CONCLUSIONS: Early exploration and debridement in equivocal (early) FG
      has a better clinical outcome with reduced hospital stay and number of
      debridement sessions than conservative treatment with delayed debridement.

PMID- 27695530
TI  - Nivolumab in the treatment of advanced renal cell carcinoma: clinical trial
      evidence and experience.
AB  - Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent
      dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine
      based immunotherapies, including interferon-alpha and interleukin-2, have been
      used for the treatment of metastatic RCC (mRCC). Long-term responses and complete
      remissions were observed, but durable clinical benefit efficacy in the overall
      population was limited and associated with significant toxicity. As a
      consequence, new generation agents targeting the vascular endothelial growth
      factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced
      interferon alpha (IFN-alpha). Strategies of tumor immune evasion include T-cell
      suppression by negative signals deriving from the interaction between programmed
      death-1 (PD-1) on the T cell and its ligand (PDL-1) on the tumor cells.
      Nivolumab, a programmed death 1 checkpoint inhibitor, blocks this pathway, thus
      reversing T-cell suppression and activating antitumor responses. The aim of this
      review is to summarize the safety and efficacy data of nivolumab in mRCC.
      Objective responses and safety profile of single-agent nivolumab are favorable in
      both previously treated and treatment-naive mRCC patients. Despite toxic effects,
      combination therapies with nivolumab have shown promising results, indicating a
      potential role in the treatment of mRCC. Tailoring immunotherapy on a patient-to
      patient basis represents a major challenge for the future.

PMID- 27695532
TI  - Role of endoscopic third ventriculostomy in tuberculous meningitis with
      hydrocephalus.
AB  - Hydrocephalus is one of the commonest complications of tuberculous meningitis
      (TBM). It can be purely obstructive, purely communicating, or due to combinations
      of obstruction in addition to defective absorption of cerebrospinal fluid (CSF).
      Endoscopic third ventriculostomy (ETV) as an alternative to shunt procedures is
      an established treatment for obstructive hydrocephalus in TBM. ETV in TBM
      hydrocephalus can be technically very difficult, especially in acute stage of
      disease due to inflamed, thick, and opaque third ventricle floor. Water jet
      dissection can be helpful in thick and opaque ventricular floor patients, while
      simple blunt perforation is possible in thin and transparent floor. Lumbar
      peritoneal shunt is a better option for communicating hydrocephalus as compared
      to VP shunt or ETV. Intraoperative Doppler or neuronavigation can help in proper
      planning of the perforation to prevent neurovascular complications. Choroid
      plexus coagulation with ETV can improve success rate in infants. Results of ETV
      are better in good grade patients. Poor results are observed in cisternal
      exudates, thick and opaque third ventricle floor, acute phase, malnourished
      patients as compared to patients without cisternal exudates, thin and transparent
      third ventricle floor, chronic phase, well-nourished patients. Some of the
      patients, especially in poor grade, can show delayed recovery. Failure to improve
      after ETV can be due to blocked stoma, complex hydrocephalus, or vascular
      compromise. Repeated lumbar puncture can help faster normalization of the raised
      intracranial pressure after ETV in patients with temporary defect in CSF
      absorption, whereas lumbar peritoneal shunt is required in permanent defect.
      Repeat ETV is recommended if the stoma is blocked. ETV should be considered as
      treatment of choice in chronic phase of the disease in obstructive hydrocephalus.

PMID- 27695531
TI  - Quantitative determination of betamethasone sodium phosphate and betamethasone
      dipropionate in human plasma by UPLC-MS/MS and a bioequivalence study.
AB  - The compound medicine of betamethasone sodium phosphate (BSP) and betamethasone
      dipropionate (BDP) is widely used for diverse glucocorticoid-sensitive acute and
      chronic diseases such as asthma, rheumatoid arthritis and systemic lupus
      erythematosus. It will be useful and beneficial to validate sensitive method for
      the determination of BSP, BDP and their metabolites for their pharmacokinetic
      study. Hereby, an ultra-high pressure liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS) has been validated for the determination of BSP, BDP
      and their metabolites betamethasone (BOH), betamethasone 17-monodipropionate
      (B17P) and betamethasone 21-monodipropionate (B21P) in human plasma. Liquid
      liquid extraction with ether and n-hexane (v/v, 4:1) was used for sample
      preparation of BDP, BOH, B17P and B21P with beclomethasone dipropionate as
      internal standard (IS), while solid phase extraction was adopted for sample
      preparation of BSP using prednisolone as IS. The chromatographic separation was
      performed on a Hypurity C18 column (150 mm*2.1 mm, 5 MUm) for BOH, BDP, B21P and
      B17P, and a Luna C18 (2) column (150 mm*2.0 mm, 5 MUm) for BSP. Electrospray
      ionization interfaced with positive multiple reaction monitoring (MRM) scan mode
      was used for mass spectrometric detection. The standard calibration curves were
      linear within the range of 2.525 * 10-9-403.9 * 10-9 mol.dm-3 for BSP, 0.125 * 10
      9-55.81 * 10-9 mol.dm-3 for BDP, 0.278 * 10-9-74.95 * 10-9 mol.dm-3 for BOH,
      0.098 * 10-9-4.688 * 10-9 mol.dm-3 for B17P and 0.226 * 10-9-5.411 * 10-9 mol.dm
      3 for B21P, respectively. The validated method was successfully applied to a
      bioequivalence study in 23 healthy subjects after they were injected with this
      compound medicine BSP and BDP.

PMID- 27695529
TI  - Oxidation-reduction potential of semen: what is its role in the treatment of male
      infertility?
AB  - The diagnosis of male infertility relies largely on conventional semen analysis,
      and its interpretation has a profound influence on subsequent management of
      patients. Despite poor correlation between conventional semen parameters and male
      fertility potential, inclusion of advanced semen quality tests to routine male
      infertility workup algorithms has not been widely accepted. Oxidative stress is
      one of the major mediators in various etiologies of male infertility; it has
      deleterious effects on spermatozoa, including DNA damage. Alleviation of
      oxidative stress constitutes a potential treatment strategy for male infertility.
      Measurement of seminal oxidative stress is of crucial role in the identification
      and monitoring of patients who may benefit from treatments. Various tests
      including reactive oxygen species (ROS) assay, total antioxidant capacity (TAC)
      assay or malondialdehyde (MDA) assay used by different laboratories have their
      own drawbacks. Oxidation-reduction potential (ORP) is a measure of overall
      balance between oxidants and antioxidants, providing a comprehensive measure of
      oxidative stress. The MiOXSYSTM System is a novel technology based on a
      galvanostatic measure of electrons; it presents static ORP (sORP) measures with
      static referring to the passive or current state of activity between oxidants and
      antioxidants. Preliminary studies have correlated sORP to poor semen qualities.
      It is potentially useful in prognostication of assisted reproductive techniques
      outcomes, screening of antioxidants either in vivo or during IVF cycles,
      identification of infertile men who may benefit from treatment of oxidative
      stress, and monitoring of treatment success. The simplified laboratory test
      requiring a small amount of semen would facilitate clinical application and
      research in the field. In this paper, we discuss the measurement of ORP by the
      MiOXSYS System as a real-time assessment of seminal oxidative stress, and argue
      that it is a potential valuable clinical test that should be incorporated into
      the male infertility workup and become an important guide to the treatment of
      oxidative stress-induced male infertility.

PMID- 27695534
TI  - Posttraumatic delayed tension pneumocephalus: Rare case with review of
      literature.
AB  - Pneumocephalus is commonly seen after head and facial trauma, ear infections, and
      tumors of the skull base or neurosurgical interventions. In tension
      pneumocephalus, the continuous accumulation of intracranial air is thought to be
      caused by a "ball valve" mechanism. In turn, this may lead to a mass effect on
      the brain, with subsequent neurological deterioration and signs of herniation.
      Tension pneumocephalus is considered a life-threatening, neurosurgical emergency
      burr-hole evacuation was performed and he experienced a full recovery. However,
      more invasive surgery was needed to resolve the condition. Delayed tension
      pneumocephalus is extremely rare and considered a neurosurgical emergency.
      Pneumocephalus is a complication of head injury in 3.9-9.7% of the cases. The
      accumulation of intracranial air can be acute (<72 h) or delayed (>=72 h). When
      intracranial air causes intracranial hypertension and has a mass effect with
      neurological deterioration, it is called tension pneumocephalus. We represent a
      clinical case of a 30-year-old male patient with involved in a road traffic
      accident, complicated by tension pneumocephalus and cerebrospinal fluid
      rhinorrhea on 1 month after trauma and underwent urgent surgical intervention.
      Burr-hole placement in the right frontal region, evacuation of tension
      pneumocephalus. Tension pneumocephalus is a life-threatening neurosurgical
      emergency case, which needs to undergo immediate surgical intervention.

PMID- 27695535
TI  - Spinal epidural angiolipomas: Clinical characteristics, management and outcomes.
AB  - PURPOSE: The spinal epidural angiolipomas are rare expansive processes made of
      mature lipomatous and angiomatous elements. They often have a benign character.
      Their etiology, pathogenesis remains uncertain, and it is a cause of spinal cord
      compression. The magnetic resonance imaging is the most important
      neuroradiological examination. Histological examination is the only examination
      to confirm the diagnosis. Surgery is the treatment of choice. METHODS: A
      retrospective study of all patients operated on for a spinal epidural angiolipoma
      at the Department of Neurosurgery at the National Institute of Neurology of Tunis
      between January 2000 and December 2014 (15 years) was performed. The aim of this
      study is to describe the clinical, radiological, histological characteristics and
      the treatment of this tumor. RESULTS: A total of nine patients were operated from
      January 01, 2000 to November 30, 2014. The average age of our patients was 51
      years with ages that ranged from 29 to 65 with a male predominance. The period
      between onset of symptoms and diagnosis ranged from 24 months with an average 12
      months. Posterior localization of the tumor was seen in all patients. Surgical
      resection was performed for all cases. The postoperative course has been
      satisfactory, with a complete recovery of neurological functions in all patients.
      CONCLUSIONS: The spinal epidural angiolipomas is rare expansive process causing
      spinal cord compression. Treatment is exclusively surgical resection. The
      functional outcome of spinal epidural angiolipomas is particularly favorable with
      a complete neurological recovery is if the patient was quickly operated.

PMID- 27695536
TI  - High incidence of neural tube defects in Northern part of India.
AB  - BACKGROUND: In the absence of primary care and prevailing associated social
      stigma, many patients of neural tube defects (NTDs) from remote areas die without
      getting any treatment. The high number of such untreated cases and unregistered
      deaths in these areas made us ponders to the fact that tertiary care center-based
      studies do not represent the true incidence of NTDs. MATERIALS AND METHODS: We
      did a population-based survey for NTDs births of rural areas from Jaunpur to
      Ghazipur district in Eastern Uttar Pradesh. These districts are among the least
      developed areas of Northern India in Uttar Pradesh among other 17. RESULTS: The
      data show an incidence of 7.48 per 1000 live births. CONCLUSION: Besides of
      unawareness regarding periconceptional folate supplementation, intensive effort
      is required to design adequately powered studies to search other key factors
      responsible for high prevalence of NTDs.

PMID- 27695537
TI  - Comparison of computational fluid dynamics findings with intraoperative
      microscopy findings in unruptured intracranial aneurysms- An initial analysis.
AB  - CONTEXT: The increase in the detection of unruptured cerebral aneurysms has led
      to management dilemma. Prediction of risk based on the size of the aneurysm is
      not always accurate. There is no objective way of predicting rupture of aneurysm
      so far. Computational fluid dynamics (CFDs) was proposed as a tool to identify
      the rupture risk. AIMS: To know the correlation of CFD findings with
      intraoperative microscopic findings and to know the relevance of CFD in the
      prediction of rupture risk and in the management of unruptured intracranial
      aneurysms. SETTINGS AND DESIGN: A prospective study involving nine cases over a
      period of 6 months as an initial analysis. SUBJECTS AND METHODS: Both males and
      females were included in the study. Preoperative analysis was performed using
      computed tomography angiogram, magnetic resonance imaging in all cases and
      digital substraction angiogram in some cases. Intraoperatively microscopic
      examination of the aneurysm wall was carried out and images recorded. The
      correlation was done between microscopic and CFD images. RESULTS: Seven cases
      were found intraoperatively to have a higher risk of rupture based on the
      thinning of the wall. Two cases had an atherosclerotic wall. All cases had low
      wall shear stress (WSS).Only two cases with atherosclerotic wall had a
      correlation with low WSS. CONCLUSIONS: While the pressure measured with CFD
      technique is a good predictor of rupture risk, the WSS component is
      controversial. Multicentric trials involving a larger subset of population are
      needed before drawing any definite conclusions. On-going development in the CFD
      analysis may help to predict the rupture chances accurately in future.

PMID- 27695538
TI  - Wall-to-lumen ratio of intracranial arteries measured by indocyanine green
      angiography.
AB  - BACKGROUND: The wall-to-lumen ratio (WLR) is an important parameter in vascular
      medicine because it indicates the character of vascular wall as well as the
      degree of stenosis. Despite the advances in medical imaging technologies, it is
      still difficult to measure the thin-walled normal intracranial arteries, and the
      reports on the WLR of normal intracranial artery are limited. It might be
      possible to calculate the WLR using the indocyanine green (ICG) angiography,
      which is used to observe intracranial vessels during microsurgery. PURPOSE: To
      evaluate the WLR of normal intracranial arteries using ICG angiography. MATERIALS
      AND METHODS: From the three cases in which ICG angiography was recorded with a
      ruler during microsurgery, 20 measurement points were chosen for the analysis.
      The ICG was injected intravenously with a dose of 0.2 mg/kg, and the vessels were
      inspected at high magnification using an operating microscope equipped with near
      infrared illumination system. The vessel outer diameter and the luminal diameter
      were measured using the images before and after the ICG arrival based on the
      pixel ratio method using a ruler as reference, respectively. The WLR was
      calculated as 0.5 * (vessel outer diameter - vessel luminal diameter). RESULTS:
      The WLR (mean +/- standard deviation) of normal intracranial arteries was 0.086
      +/- 0.022. The WLR tended to be high in small arteries. CONCLUSION: The WLR of
      normal intracranial arteries calculated using ICG angiography was consistent with
      the WLR reported in the previous reports based on human autopsy.

PMID- 27695533
TI  - Chronic subdural hematoma.
AB  - Chronic subdural hematoma (CSDH) is one of the most common neurosurgical
      conditions. There is lack of uniformity in the treatment of CSDH amongst surgeons
      in terms of various treatment strategies. Clinical presentation may vary from no
      symptoms to unconsciousness. CSDH is usually diagnosed by contrast-enhanced
      computed tomography scan. Magnetic resonance imaging (MRI) scan is more sensitive
      in the diagnosis of bilateral isodense CSDH, multiple loculations, intrahematoma
      membranes, fresh bleeding, hemolysis, and the size of capsule. Contrast-enhanced
      CT or MRI could detect associated primary or metastatic dural diseases. Although
      definite history of trauma could be obtained in a majority of cases, some cases
      may be secondary to coagulation defect, intracranial hypotension, use of
      anticoagulants and antiplatelet drugs, etc., Recurrent bleeding, increased
      exudates from outer membrane, and cerebrospinal fluid entrapment have been
      implicated in the enlargement of CSDH. Burr-hole evacuation is the treatment of
      choice for an uncomplicated CSDH. Most of the recent trials favor the use of
      drain to reduce recurrence rate. Craniotomy and twist drill craniostomy also play
      a role in the management. Dural biopsy should be taken, especially in recurrence
      and thick outer membrane. Nonsurgical management is reserved for asymptomatic or
      high operative risk patients. The steroids and angiotensin converting enzyme
      inhibitors may also play a role in the management. Single management strategy is
      not appropriate for all the cases of CSDH. Better understanding of the nature of
      the pathology, rational selection of an ideal treatment strategy for an
      individual patient, and identification of the merits and limitations of different
      surgical techniques could help in improving the prognosis.

PMID- 27695539
TI  - Factors affecting outcome in poor grade subarachnoid haemorrhage: An
      institutional study.
AB  - CONTEXT: Poor grade subarachnoid hemorrhage (SAH) is usually associated with
      unfavorable outcomes and optimal management is deemed complicated. Most centres
      follow an expectant management strategy or a less aggressive approach till
      patients improve to good clinical grades. This approach has been associated with
      higher mortality and morbidity. However, not all patients with poor clinical
      condition fare badly. Identification and early aggressive management of this
      select group of patients may lead to favorable outcomes. SETTINGS AND DESIGN:
      Prospective non-randomized study. MATERIALS AND METHODS: We prospectively
      analyzed 19 cases presented in WFNS grade 4 and 5 and factors affecting their
      outcome at a tertiary care centre in south India. This study was aimed at
      identifying those few poor grade patients who are probable candidates for a good
      outcome. STATISTICAL ANALYSIS USED: All the variables were analyzed for possible
      correlations with the SPSS version 13 software. The Chi-square test with a P <
      0.05 was taken as statistically significant. RESULTS: Of 19 cases, 13 were
      operated and good outcome was seen in 53.8% of the patients who underwent surgery
      and aggressive management. All 7 patients who were managed conservatively died.
      15.8% of the patients had low density changes (P = 0.625). Absence of such
      changes was associated with a good long term outcome (P = 0.004). 9 patients had
      intraventricular hemorrhage at presentation and 5 patients having hydrocephalus
      underwent extra-ventricular drainage. Statistically significant factors
      precluding good outcome were the presence of infarcts and thick SAH in the
      cisterns. CONCLUSIONS: Poor grade (WFNS 4 and 5) SAH patients with or without
      ICH, IVH, if operated within 3 days can give rise to favorable outcome in around
      50%. However, presence of patchy infarcts associated with thick subarachnoid
      blood (Fisher grade 3) precludes long term survival or meaningful recovery.
      Hence, aggressive management is unlikely to alter the natural history of such
      patients.

PMID- 27695540
TI  - Comprehension and compliance with the discharge advice and quality of life at
      home among the postoperative neurosurgery patients discharged from PGIMER,
      Chandigarh, India.
AB  - PROBLEM STATEMENT: Neurosurgical patients require special care not only in the
      hospital but also after their discharge from the hospital. Comprehension and
      compliance to the instructions given by the doctors/nurses at the time of
      discharge is important in home care of these patients. Many such patients suffer
      from various co-morbidities. Variable periods of convalescence affect health
      related quality of life in these patients. PURPOSE OF THE STUDY: To determine the
      degree of compliance of neurosurgery patients and their family caregivers with
      the discharge advice given by the consultantsTo evaluate the quality of life of
      these patientsTo know the problems faced by these patients at home. MATERIALS AND
      METHODS: This cross-sectional interview-based descriptive study was conducted in
      2010 in Chandigarh. These patients were visited at their home. A scale was
      evolved to evaluate comprehension and compliance to the advice given at the time
      of discharge, according to the criteria developed by Clark et al. Lawton Brody
      instrumental activity of daily life and Spitzer quality of life index were used
      to assess patients' quality of life after the operation. Verbatim responses were
      recorded for the purpose of qualitative research. RESULTS: Overall, 58 patients
      and their caregivers were interviewed at home. Mean age of the patients was 38.9
      years. Out of 37 patients, 35 showed good comprehension and 33 patients had a
      good compliance with the instructions given for medication. The condition of
      74.1% patients improved after the operation. Depression was reported in 31% of
      the patients. Many (36.2%) patients had to quit their job due to the disease.
      Almost half (47.4%) of the patients were independent in daily activities of their
      life while being evaluated on Barthel activity of daily life index. CONCLUSION
      AND RECOMMENDATIONS: It is in the long term that the true complexity and impact
      of operations become apparent. After operation, such patients are likely to have
      a range of physical, emotional, cognitive, behavioral, and social problems, which
      may result in difficulties for both patients and their family caregivers.
      Provision of mechanism of prioritized follow-up care to the operated bedridden
      neurosurgery patients should be made.

PMID- 27695541
TI  - Evaluation of modified Kumar and Kalra myelopathy scoring system in sub-axial
      spinal pathologies.
AB  - BACKGROUND: Various pathologies affect the spine, but these lesions present with
      more or less similar clinical profile. The present functional scoring systems are
      inadequate and insensitive to changes in neurological status of the patient.
      OBJECTIVE: Our study aims to assess the modified Kumar and Kalra (K and K)
      scoring system in patients with pathologies in the sub-axial spine. MATERIALS AND
      METHODS: A total of 78 consecutive patients from the period of January 2009 to
      June 2010 were prospectively included in the study. These patients were operated
      by the senior author at our institute. The mean Modified Japanese Orthopaedic
      Association (MJOA) score and the mean modified K and K score were calculated in
      the preoperative, at the time of discharge (post-surgery), and at 3 months and 6
      months follow-up. RESULTS: There were 57 male (73.01%) patients and 21 female
      patients (26.92%), with the mean age of presentation of 39.20 years (+/-14.12
      years) and a range of 9-75 years. Out of the total 78 patients, 60 patients had
      pathology in the cervical spine (sub-axial spine) and 18 patients had pathology
      in the dorsal spine. Majority of the patients had motor and sensory symptoms. The
      mean preoperative modified K and K score was 17.38 (+/-3.18) and the mean
      preoperative MJOA score was 11.21 (+/-2.12). The K and K score was able to
      predict the correct outcome in 70 patients (89.74%), whereas the MJOA score was
      able to predict correctly in 62 patients (79.49%). CONCLUSION: The modified K and
      K score has a better predictive value than the MJOA score.

PMID- 27695542
TI  - Intracranial abscesses: Retrospective analysis of 32 patients and review of
      literature.
AB  - BACKGROUND: Intracranial abscess collections, though uncommon, are dreaded
      complications of head trauma, neurosurgical operations, meningitis, and otogenic,
      mastoid, and paranasal air sinus infections. Combining surgical evacuation with
      the appropriate antibiotic therapy is the effective treatment for intracranial
      abscesses. However, literature on surgical treatment is replete with several
      procedures which, on their own, may not. OBJECTIVES: To determine the
      epidemiology and outcomes (of various treatment modalities) of intracranial
      abscesses in our institution, a major referral center for neurosurgical
      conditions in the midwestern region of Nigeria. MATERIALS AND METHODS: This is a
      retrospective analysis of demographic data as well as indications, treatment
      modalities, and outcomes of various surgical procedures for evacuation of
      intracranial abscesses between September 2006 and December 2011. RESULTS: We
      carried out 40 procedures in 32 (23 male and 9 female) patients with various
      intracranial abscesses. These represented approximately 5.6% of all operative
      neurosurgical procedures in our unit since inception. Most abscesses [16, i.e.
      50%] occurred in the second decade. In the first decade, there were 7 (22%), and
      after the age of 30 years, there were 4 (12.5%). The most susceptible single year
      of life was infancy with 4 (12.5%) cases of intracranial abscesses. None of the
      infants had features of congenital heart disease. The predisposing factors were
      mostly otolaryngologic (9) or posttraumatic (6). Most abscesses (41%) were
      located in the frontal region, and intraparenchymal (i.e. intracerebral or
      intracerebellar) (50%) lesions were commoner than extradural, subdural, or
      intraventricular lesions. The commonest procedure performed (50%) was burr hole
      evacuation. Four patients (12.5% of cases) died. Prognosis appears to worsen with
      meningitis as the predisposing infection, ventriculitis, multiple abscesses
      especially in infants, and immunosuppression. CONCLUSION: The relative rarity of
      intracranial abscesses and the frequent delays in making the diagnosis render the
      condition a significant challenge to the clinician. A high index of suspicion,
      close interaction between the neurosurgeon and infectious disease specialist,
      with early treatment by adequate abscess drainage and appropriate antimicrobial
      treatment are important in their management.

PMID- 27695543
TI  - Traumatic tentorial hematoma in two-wheeler riders: Correlation with helmet use.
AB  - BACKGROUND: Tentorial hematoma is frequently seen in traumatic brain injury (TBI)
      patients, especially in motorized two-wheeler riders following head injury.
      However its relevance and prognostic significance are not known. OBJECTIVE: To
      evaluate patients of TBI with tentorial hematoma using a simple grading system
      and attempt to correlate this grading with factors like helmet use and
      neurological outcome. MATERIALS AND METHODS: This prospective study over a 1-year
      period included patients with TBI who had tentorial hematoma in the initial plain
      head. Patients were divided into three grades based on the initial CT findings:
      Grade I: Isolated tentorial hematoma, grade II: tentorial hematoma with midline
      shift but open cisterns and grade III: Tentorial hematoma with effaced cisterns.
      Clinical and radiological records of patients including admission GCS and GOS at
      discharge were assessed in all cases. OBSERVATIONS: A total of 1786 patients of
      TBI were admitted during the study period. Of these, 106 (5.9%) patients had
      tentorial hematoma. 84.9% (n = 90) were male and 15.1% (n = 16) were female with
      the mean age being 36.5 years (range 2-66 years). The mean admission GCS was 13,
      11 and 8 in patients with grade I, II and III tentorial hematoma respectively.
      43.4% (n = 46) of the patients had grade I, 32.1% (n = 34) had grade II and 24.5%
      (n = 26) patients had grade III tentorial hematoma. Seventy-one patients (84.5%)
      were riding motorized two wheelers with 63 (89%) wearing helmets. The majority of
      the patients wearing helmets (58.8%) had grade I hematoma with 35% (n = 22)
      having grade II hematoma and only 6.3% (n = 4) having grade III hematoma.
      Overall, there were 20 deaths. 50% (n = 10) of the deaths were in patients with
      grade III hematoma and 40% (n = 8) of the deaths were in patients with grade II
      hematoma. There were two (10%) deaths in patients with grade I hematoma (both
      unrelated to head injury). The mean GOS at the time of discharge was 5, 4.1 and
      2.2 in patients with grade I, II and III tentorial hematoma, respectively.
      CONCLUSIONS: Tentorial hematomas are very common in two-wheeler riders with TBI
      and could be a marker for indirect forces such as rotational forces experienced
      while wearing helmets.

PMID- 27695544
TI  - Role of effective canal diameter in assessing the pre-operative and the post
      operative status of patients with bony cranio-vertebral anomalies.
AB  - INTRODUCTION: The effective canal diameter (ECD) for the cranio-vertebral
      junction is measured from the posterior surface of the dens to the nearest
      posterior bony structure (foramen magnum or the posterior arch of the atlas). The
      ECD is the space which is occupied by the buffer space (which can be compromised
      without producing any signs or symptoms) and the cord itself. We intend to study
      the role of the ECD (especially in patients with markedly reduced ECD) in
      producing the symptoms and also the outcome of surgery in patients with bony
      cranio-vertebral junction (CVJ) anomalies. MATERIALS AND METHODS: A total of 67
      consecutive patients from the period of January 2009 through June 2010 were
      prospectively included in the study. These patients were operated by a single
      experienced surgeon (the senior author) at the Sanjay Gandhi Post Graduate
      Institute of Medical Sciences, Lucknow. The ECD and the pre-operative Kumar and
      Kalra score (K and K score) (4) was calculated for all patients. The K and K
      score was also calculated at the time of discharge, at three months and six
      months follow-up. The patients were divided into three groups based on the ECD
      into 5 mm to 10 mm group, 10 mm to 15 mm group, and >15 mm group. RESULTS: There
      were 53 male (79.1%) patients and 14 female patients (20.9%) with mean age of
      presentation 27.10 years (+/-15.01 years) with range of 4-59 years. The duration
      of symptoms in our series varied from 1-120 months with mean of 23.79 months. The
      mean effective canal diameter was 9.027 mm (+/-2.23 mm) with range of 5-16 mm.
      The mean pre-operative K and K score was 19.27 (+/-4.19). There were 39 patients
      who had an ECD between 5 mm to 10 mm, 24 patients with ECD between 10 mm to 15
      mm, and 4 patients with ECD more than 15 mm. The correlation coefficients between
      the effective canal diameter and the pre-operative and the post-operative Kumar
      and Kalra score at the time of discharge, 3 months and 6 months were 0.404 (P <
      0.001), 0.320 (P < 0.008), 0.0302 (P < 0.013), and 0.284 (P < 0.020),
      respectively. The ECD and the pre-operative score were most significantly and
      strongly related to each other in patients with ECD between 5-10 mm. CONCLUSION:
      The ECD is significantly related to the pre-operative status (K and K score) of
      the patient. This correlation was strongest in the group with ECD of 5-10 mm. It
      was also observed that as the follow-up increased, the correlation between the
      ECD and the post-operative K and K score became less stronger though they
      remained significantly related to each other.

PMID- 27695545
TI  - Facial functional outcome in monitored versus not-monitored patients in
      vestibular schwannomas surgery.
AB  - OBJECTIVE: Even though advances in surgical techniques have improved facial nerve
      outcomes, functional preservation is still an issue because injury to the facial
      nerve has significant physical and psychological consequences for the patient. We
      retrospectively review our data in VS surgery to compare the facial outcome in
      intraoperative facial monitored versus not-monitored patients. MATERIALS AND
      METHODS: 51 consecutive patients with unilateral vestibular schwannoma in the
      period from 2005 to 2010 were treated in our Institution. In according to the
      type of neurophysiological tool used during surgical procedures, two patients
      groups were identified: Group 1 (facial stimulator only) and Group 2 (stimulator
      and facial monitoring). Statistical comparison of the two groups was made with
      the t- test, and facial function results were evaluated with the Fisher's exact
      test. RESULTS: In the Group 1, of the 22 patients with anatomically preserved
      facial nerves, 3 (13.6%) showed excellent facial nerve function, 14 (63.6%)
      showed intermediate function, and 5 (22.7%) showed poor function. In the Group 2,
      all the 27 patients got anatomically preserved facial nerves, and 18 (66.7%)
      showed excellent facial nerve function, 9 (33.3%) showed intermediate function,
      and no one showed poor function. CONCLUSIONS: We found that retrosigmoid approach
      associated with continuous EMG facial monitoring combined with the use of bipolar
      stimulation is a safe and effective treatment for vestibular schwannomas.

PMID- 27695547
TI  - Localized reversible high signal intensities on diffusion-weighted MRI in
      hypoglycemia: A study of 70 cases.
AB  - INTRODUCTION: It is well-known that localized reversible high signal intensities
      in the splenium of the corpus callosum or the basal ganglia appear on diffusion
      weighted MRI in the presence of hypoglycemia. The aim of this study was to
      clarify the incidence and significance of such high signal intensity lesions.
      RESULTS: We analyzed 70 cases of hypoglycemia with consciousness disturbance
      referred to our outpatient office. Localized reversible high signal intensities
      on diffusion-weighted MRI were noted in 6 cases (8.6%). They were at the splenium
      of the corpus callosum in four cases (5.7%), and right frontal cortex and
      bilateral frontal white matter in one each. Convulsions were noted in five cases,
      and right hemiparesis was noted in three. None of the three cases of hemiparesis
      showed localized reversible high signal intensities on diffusion-weighted MRI.
      These lesions are reversible if the patients undergo treatment without delay.
      CONCLUSION: The significance of these lesions is still unclear. However, when a
      high signal intensity lesion that is not reasonable for the symptom is detected
      on diffusion-weighted MRI, an immediate check of the blood sugar level is
      mandatory.

PMID- 27695546
TI  - Ganglioglioma: Single-institutional experience of 24 cases with review of
      literature.
AB  - BACKGROUND: Ganglioglioma is a common seizure associated tumor. The goal of this
      study was to observe the postoperative outcome in patients with gangliogliomas.
      MATERIAL AND METHODS: A total 24 patients with gangliogliomas who underwent
      surgery at our institute from 2008 to 2011 were included. There were 13 males
      (54%) in our study. A retrospective analysis for the demographic profile, surgery
      and outcome was performed using STATA software. Literature on this subject was
      also reviewed, MEDLINE and PUBMED databases were searched. OBSERVATIONS: Sixteen
      patients presented with signs and symptoms of raised intracranial pressure and 12
      patients had seizure disorder. Average age at surgery was 20 years (range 7-50
      years). Twelve each were located in the temporal lobe and extra-temporal
      location. Intra-operative electrocorticography (ECoG) alone in three and image
      guidance alone were used in two patients, respectively. Both ECoG and image
      guidance were used in one patient and none of them was used in 18 patients. Gross
      total resection was achieved in 17 patients. After a mean follow-up of 1.6 years
      (range 3 months to 2.5 years), out of 12 patients with preoperative seizures, 10
      (83.3%) were seizure free (Engel class-I) and 2 (16.6%) belonged to Engel class
      II. None of the factors, including age at surgery, seizure duration prior to
      surgery, type of seizures, use of intra-operative ECoG and image guidance, extent
      of tumor resection, and surgical strategy proved to have significant correlation
      with postoperative seizure outcome. CONCLUSIONS: Surgical treatment is effective
      and safe for patients with gangliogliomas. Neither intra-operative ECoG nor image
      guidance necessarily leads to better seizure control, although they are useful
      adjunct for achieving safe and complete tumor resection.

PMID- 27695548
TI  - A cost effectiveness based safety and efficacy study of resterilized intra
      parenchymal catheter based intracranial pressure monitoring in developing world.
AB  - BACKGROUND: The management of traumatic brain injury (TBI) aims to maintain the
      normal cerebral perfusion in spite of the mass lesions that may occur (haematoma,
      contusion, and oedema). The monitoring of the intracranial pressure (ICP) is a
      step in that direction. The intra-parenchymal catheters have the lowest incidence
      of infection compared to intra-ventricular/subdural catheters with reliable and
      accurate pressure recordings. The major disadvantage of the intra-parenchymal
      catheters is the cost, especially in developing nations. HYPOTHESIS: Resterilized
      intra-parenchymal strain gauge catheters can be used safely for ICP monitoring
      without any added risk of meningitis. The reusage of catheters can bring down the
      costs. Resterilized catheters/equipment have been approved for usage in cardiac
      usage, but such study on ICP catheters has not been carried out so far in any
      part of the world. METHODOLOGY: A total of 100 consecutive cases of severe TBI
      receiving ICP monitoring at a level 1 trauma center of a developing nation were
      prospectively studied (34 cases had fresh catheters, and 66 had resterilized
      [using ethylene oxide] catheters). OBSERVATIONS: The use of reused resterilized
      catheters was not associated with increased incidence of meningitis or fever (the
      surrogate marker for infection in this study). Also, there was concordance
      between the pressure recording of reused catheters and operative
      finding/subsequent computed tomography scans. These catheters after sterilization
      could be reused 2-4 times and reliably recorded the ICP (insignificant drift)
      with no increase in the incidence of meningitis. CONCLUSIONS: Usage of
      resterilized intra-parenchymal ICP catheters is feasible, safe, efficacious, and
      cost effective and brings down the cost of monitoring significantly.

PMID- 27695549
TI  - Learning neuroendoscopy with an exoscope system (video telescopic operating
      monitor): Early clinical results.
AB  - CONTEXT: Steep learning curve is found initially in pure endoscopic procedures.
      Video telescopic operating monitor (VITOM) is an advance in rigid-lens telescope
      systems provides an alternative method for learning basics of neuroendoscopy with
      the help of the familiar principle of microneurosurgery. AIMS: The aim was to
      evaluate the clinical utility of VITOM as a learning tool for neuroendoscopy.
      MATERIALS AND METHODS: Video telescopic operating monitor was used 39 cranial and
      spinal procedures and its utility as a tool for minimally invasive neurosurgery
      and neuroendoscopy for initial learning curve was studied. RESULTS: Video
      telescopic operating monitor was used in 25 cranial and 14 spinal procedures.
      Image quality is comparable to endoscope and microscope. Surgeons comfort
      improved with VITOM. Frequent repositioning of scope holder and lack of
      stereopsis is initial limiting factor was compensated for with repeated
      procedures. CONCLUSIONS: Video telescopic operating monitor is found useful to
      reduce initial learning curve of neuroendoscopy.

PMID- 27695550
TI  - Prolonged bradycardia, asystole and outcome of high spinal cord injury patients:
      Risk factors and management.
AB  - BACKGROUND: High spinal cord injury (HSCI) is one of the devastating traumatic
      injuries. 80% of these patients are young male, and 93% will have major
      neurological disabilities. There is a paucity of literature about prolonged
      bradycardia in HSCI patients. The aim of this study was to know the prevalence,
      risk factors, precipitating factors for prolonged bradycardia in the HSCI
      patients. MATERIALS AND METHODS: All patients who were admitted to the Intensive
      Care Unit (ICU) of a tertiary hospital, with spinal cord injury above level of
      dorsal (D4) were enrolled in this study prospectively. Patient's demographic
      data, mechanism, level and type of spinal injury, associated injuries, injury
      severity score (ISS), spinal shock, vasopressors used, time of occurrence of
      bradycardia, treatment for bradycardia, precipitating as well as risk factors and
      outcome were recorded. RESULTS: During the study period, a total of 138 patients
      were admitted to the ICU with HSCI. Majority of patients were male. The most
      frequently associated injury in these patients was skeletal fractures (38.4%).
      Most common complication was pneumonia 56 (41%). Forty-five (33%) of the total
      patients had prolonged bradycardia; 87% of these patients had pneumonia when
      bradycardia occurred. 53.4% had cardiac asystole. 29 (21%) patients had
      bradycardia at the time of endotracheal suctioning, whereas 27 (20%) patients
      developed bradycardia at the time of positioning. Majority of the patients were
      managed conservatively. Those HSCI patients who developed prolonged bradycardia,
      their ISS score was statistically higher, ICU and hospital stay was significantly
      higher compared with those HSCI patient who did not have prolonged bradycardia.
      Multivariate analysis revealed that hypotension on admission; pneumonia, and
      tracheostomy were risk factors for the development of prolonged bradycardia in
      HSCI patients. CONCLUSION: Prolonged bradycardia was associated with
      significantly higher incidence of asystole. Endotracheal suctioning and
      positioning of HSCI patients were significant provocative factors for prolonged
      bradycardia; hypotension on admission, pneumonia and tracheostomy were the risk
      factors for the development of prolonged bradycardia in these patients.

PMID- 27695552
TI  - Primary spinal tumors in childhood: A single institution 15 year experience.
AB  - BACKGROUND: Pediatric primary spinal tumors (PST) are fairly uncommon, with
      little available data regarding incidence and outcomes. MATERIALS AND METHODS: We
      conducted a retrospective review of the 22 consecutive patients less than 18
      years old diagnosed with PST between March 1997 and May 2011 and treated at Chang
      Gung Children Hospital. All patients had undergone magnetic resonance imaging
      (MRI) for pre-operative evaluation and operations for PST. The extent of tumor
      removal was assessed by surgical report by the neurosurgeon or by post-operative
      MRI if available. RESULTS: Ten of them had intramedullary tumors and 12 had
      intradural extramedullary tumors. All patients were treated with surgery to the
      primary site. A total of 15 patients underwent gross total tumor resection and
      seven patients received post-operative radiotherapy. Five patients received
      adjuvant chemotherapy for their primary tumor. Fourteen patients (64%) survived
      from study entry without tumor progression. CONCLUSIONS: PST encompassed a
      diverse group of pathologic entities that differ markedly based on the location
      and age of the children. Total resection of pediatric PST in children could be
      performed with acceptable risk and satisfactory long-term results.

PMID- 27695551
TI  - Sellar repair with autologous muscle and composite septal cartilage grafts for
      treatment of cerebrospinal fluid leakage following trans-sphenoidal pituitary
      surgery.
AB  - CONTEXT: Many reconstructive techniques have been proposed to prevent
      postoperative cerebrospinal fluid (CSF) leakage after trans-sphenoidal pituitary
      surgery. However, no total agreement has been reached to the best technique. AIM:
      Assessment of the efficacy of sellar repair with autologous muscle and composite
      septal cartilage grafts for treatment of intraoperative and delayed postoperative
      CSF leakage following trans-sphenoidal pituitary surgery without the use of
      postoperative external lumbar CSF drain. STUDY DESIGN: This is a retrospective
      case series study, level IV evidence. MATERIALS AND METHODS: : Twenty three
      patients were involved in this study. Seventeen patients had intraoperative CSF
      leakage and were treated immediately by our technique. Six patients had
      postoperative CSF rhinorrhea and had delayed treatment with our technique after
      failure of conservative measures and external lumbar CSF drainage for more than
      three days. The technique involved intradural placement of autologous muscle
      graft supplemented with extradural composite septal cartilage graft, composed of
      a piece of the posterior cartilaginous septum with its covering mucoperichondrium
      on one side only to fit into the sellar defect as a double layer button. RESULTS:
      CSF leak was of grade 1 in 6 patients (26.1%), grade 2 in 10 patients (43.5%) and
      grade 3 in 7 patients (30.4%). None of the patients in our study had
      postoperative CSF leak after the use of our technique during the follow up period
      (mean 24 +/- 10.47 standard deviation months). None of the patients developed
      treatment-related complications. All the patients had well developed mucosal
      covering of the sellar defect after two months. CONCLUSION: Our technique of
      sellar repair by using autologous muscle and composite septal cartilage grafts is
      effective in treatment of intraoperative and delayed postoperative CSF leakage
      following trans-sphenoidal pituitary surgery without the use of postoperative
      external lumbar CSF drain even in the high-output CSF leaks.

PMID- 27695553
TI  - Primary non-Hodgkin's lymphoma of the skull with extra and intracranial extension
      presenting with bulky scalp mass lesion.
AB  - Primary non-Hodgkin's lymphoma (NHL) of the cranium with extra- and intracranial
      extension without systemic or skeletal manifestation in a non-immunocompromised
      patient is extremely rare. These lesions are most of the time misdiagnosed
      because they mimic other conditions like meningioma. Here, we report a case
      presented with huge bulky scalp mass which on magnetic resonance imaging (MRI)
      brain showed involvement of scalp, cranial vault, meninges, and the brain
      parenchyma, mimicking a meningioma. After gross total resection, biopsy and CD
      marker study revealed primary non-Hodgkin's diffuse large B-cell lymphoma
      (DLBCL). Malignant NHL should be considered in differential diagnosis of bulky
      scalp mass lesion.

PMID- 27695554
TI  - Primary aneurysmal bone cyst of the petrous temporal bone: A case report and
      review of literature.
AB  - Aneurysmal bone cyst (ABC) arising in the petrous portion of the temporal bone is
      a rare entity with only five such reported cases in the literature. We report the
      case of a 28-year-old man who presented with a tender swelling in the right
      preauricular region with right ear discharge and conductive hearing loss of 4
      years' duration. Computed tomography and Magnetic Resonance imaging showed a
      destructive lesion in the right petrous bone with cavitation consistent with the
      diagnosis of ABC. Gross total resection of the lesion was achieved and diagnosis
      was confirmed histologically. The patient had no recurrence at 12 months of
      follow-up. This report presents the unusual location of an uncommon bony tumor
      with a review of its clinical, radiological, and histopathological features as
      well as the treatment modalities available.

PMID- 27695555
TI  - Calvarial tubercular osteomyelitic abscess in an elderly.
AB  - Tuberculous osteomyelitis of skull is very rare, even in areas where tuberculosis
      is endemic. We herein describe an elderly woman who was apparently
      immunocompetent and presented with left frontal scalp swelling and right cervical
      lymphadenopathy. CT scan showed irregular bony destruction of the frontal bone.
      MRI revealed a large extradural, multiseptate, solid-cystic lesion with
      peripheral enhancement. FNAC from the lesion showed granulomas with caseation
      suggestive of tuberculosis. The lesion was debrided and she was started on anti
      tubercular therapy. Deterioration of liver parameters led to change from primary
      drugs to liver-friendly, anti-tubercular agents. Though anti-tubercular therapy
      is the mainstay of calvarial tuberculosis, surgical debridement reduces the
      bacterial burden and probably hastens recovery.

PMID- 27695556
TI  - Spontaneous recovery of post-traumatic acute bilateral facial and abducens nerve
      palsy.
AB  - Bilateral abducens and facial palsy following head injury are extremely rare. We
      present a patient with post-traumatic bilateral facial and abducens palsy. There
      were bitemporal fractures that did not correspond with the facial canal. Despite
      complete facial palsy with axonal degeneration and > 90% facial muscle
      degenervation, conservative management helped. This report highlights the
      importance of conservative management in post-traumatic complete facial palsy
      especially when the fracture line does not correspond with the facial canal.

PMID- 27695557
TI  - Baastrup's disease in the pediatric spine.
AB  - Baastrup's disease is an uncommon entity in the elderly spine and it is very rare
      in the pediatric age group. There are only few case reports in the literature
      containing Baastrup's disease in pediatric spine. Baastrup's disease is also
      known as kissing spine because the posterior spinous processes touch or "kiss"
      one another, characterized by enlarged posterior spinous projections with normal
      neuroforamina and normal spinal disk height. There are various pathological and
      etiological hypotheses behind Baastrup's disease. Backache is one of the most
      common causes of morbidity in these patients and but sometimes patient can be
      asymptomatic with or without swelling on the back. Here, we present a case of 10
      year-old female child with silent swelling on low back region diagnose as
      Baastrup's disease.

PMID- 27695558
TI  - Delayed intracerebellar hemorrhage secondary to lumboperitoneal shunt insertion.
AB  - Aim of this paper is to present and discuss a case of a delayed cerebellar
      parenchymal hemorrhage developing after L/P shunt placement with a NPH patient. A
      hypertensive patient admitted to our clinic with a diagnosis of NPH. The patient
      was placed a pressure adjustable L/P shunt without any surgical complication. He
      was discharged with an uneventful period. The patient was admitted to the
      emergency clinic of our hospital with a 1.5 * 1.5 cm diameter hematoma at the
      left cerebellar hemisphere on 2 days after his discharge. CSF drainage by an L/P
      shunt can generate intracerebellar hemorrhages especially in hypertensive
      patients.

PMID- 27695559
TI  - Lymphoplasmacyte-rich meningioma with invasion of bone: A case report and review
      of literature.
AB  - Lymphoplasmacyte-rich (LPR) meningioma is a rare variant of meningioma, which is
      characterized by conspicuous infiltration of plasma cells and lymphocytes and a
      variable proportion of meningothelial elements, and is classified as a grade I
      tumor in World Health Organization (WHO) classification of tumors of central
      nervous system. The origin and biological behavior of this rare variant of
      meningioma is still not clear. Till date, very few cases of LPR meningioma have
      been reported globally. Here, we are presenting a case of right parietal
      convexity LPR meningioma with invasion of bone in a 32-year-old male patient, who
      presented to us with complaints of focal seizures and weakness in left upper
      limb.

PMID- 27695560
TI  - Late onset of subdural hematoma after bifrontal contusion.
AB  - Cerebral cortical contusions are one of the most common computed tomography
      findings in head-injured patients and common sequel of traumatic brain injury.
      These contusions tend to show a progressive increase in mass effect on repeated
      imaging, most small contusions do not require surgical evacuation. However,
      progression to subdural hematoma (SDH) in a late aspect is unique. Here we
      present a 71-year-old man with bifrontal contusion, who deteriorated 43 days
      after initial trauma with sudden onset of acute SDH. This unusual case suggests
      that neurosurgeons should be alert for the possibility of very late onset of
      acute SDH after bifrontal contusions.

PMID- 27695562
TI  - Postoperative seizure following transforaminal percutaneous endoscopic lumbar
      discectomy.
AB  - Endoscopic surgery for lumbar disc herniation has been available for more than 30
      years. Transforaminal percutaneous endoscopic lumbar discectomy is a well-known,
      safe, and effective method used for the treatment of the lumbar disc herniation.
      The published complications of the transforaminal percutaneous endoscopic lumbar
      discectomy consist of infections, thrombophlebitis, dysesthesia, dural tear,
      vascular injury, and death. Seizure after transforaminal percutaneous endoscopic
      lumbar discectomy is an extremely rare complication. A 20-year-old patient
      applied at our department who had undergone transforaminal percutaneous
      endoscopic lumbar. During the procedure, while performing the discography, non
      ionic contrast media was administered into the thecal sac inadvertently. Two
      hours after surgery, the patient developed generalized tonic-clonic seizure of 5
      min duration. Diagnosis of iohexol-induced seizure was made and the patient was
      treated supportively without anti-epileptics. Here we present the first case of
      seizure after transforaminal percutaneous endoscopic lumbar discectomy, which was
      caused by inadvertent administration of the contrast media into the thecal sac.

PMID- 27695561
TI  - Solitary fibrous tumor of the sellar region treated with adjuvant radiation
      therapy.
AB  - The solitary fibrous tumor of central nervous system is rare. Herein, a case of
      solitary fibrous tumor arising from sellar region is described. A 60-year-old man
      underwent subtotal excision of the tumor because of extensive infiltration of
      optical and vascular structures. In view of the presence of residual tumor, he
      was treated with adjuvant radiation therapy. After a follow-up period of 1 year,
      there was no progression of the lesion evident on magnetic resonance imaging of
      the brain. Solitary fibrous tumor should be considered as one of the differential
      diagnosis of a mass lesion arising in sellar region. Immunohistochemistry with
      CD34 is valuable for discerning the diagnosis. Complete surgery should be the
      goal of treatment and adjuvant radiation therapy may be considered for residual
      or recurrent disease.

PMID- 27695563
TI  - Osteoblastic meningioma with turtle shell: Different entity from calcified
      meningioma.
AB  - Bone formation within meningioma is secondary to metaplasia of the meningothelial
      cells into osteoblastic cells. This needs to be differentiated form the commonly
      seen calcification. We describe a rare case of osteobalstic meningioma in which
      bony trabeculae were seen within meningothelial cells.

PMID- 27695564
TI  - Recurrence of spinal schwannoma: Is it preventable?
AB  - Spinal schwannomas account for about 25% of primary intradural spinal cord tumors
      in adult. The prognosis for spinal schwannomas is excellent in most cases.
      Complete resection is curative. However following subtotal removal, recurrence
      develops after several years. We describe a case of recurrent spinal schwannoma
      who had been operated twice before for same disease. The possible cause of
      recurrence and difficulties in reoperation are discussed.

PMID- 27695565
TI  - Coexistent dysembryoplastic neuroepithelial tumour and pilocytic astrocytoma.
AB  - Dysembryoplastic neuroepithelial tumour (DNET) is an uncommon mixed glioneuronal
      tumour. DNET is classified as Grade I neoplasm in revised World Health
      Organization classification of tumors of the nervous system. DNET is commonly
      seen in the temporal lobe of children and young adults with features of
      pharmacoresistant complex partial seizures. Tumors arising in association with
      DNETs are rare. Only two cases of pilocytic astrocytoma (PA) arising in DNETs are
      reported. Surgical excision is the only successful management with favourable
      prognosis. The development of recurrence and malignancy after subtotal or even
      after complete excision challenges the premise of stability and highlights the
      importance of close clinical follow up. Here, a case of DNET with area of PA is
      described which helps in understanding the pathogenesis and biological behavior
      of DNET.

PMID- 27695566
TI  - A case of symptomatic synchronous cervical and cerebellar metastasis after
      resection of thoracal metastasis from temporal glioblastoma multiforme without
      any local recurrence.
AB  - Glioblastoma multiforme (GBM) is the most common and the most malignant primary
      intracranial tumor in adults and it is usually occurs between the age of 40 and
      60 years. It is local invasive and recurrent tumor and hence that has a poor
      prognosis. However, recent advances in tumor surgery, irradiation and
      chemotherapeutic agent permit long survival and metastasis which is symptomatic.
      Previously studies reported spinal metastasis, but we report a first case of
      synchronous symptomatic cerebellar and cervical spinal metastasis after resection
      of symptomatic thoracic spinal metastasis from temporal GBM without any
      recurrence of excision areas.

PMID- 27695567
TI  - Anterior cervical discectomy and fusion with titanium cages for simple or
      multilevel herniated discs and spur of the cervical spine: Report of 2 cases and
      experience in Bali.
AB  - This report presents two cases of cervicobrachialgia and radiculopathy due to
      multiple cervical herniated discs and spur formation that dealt with anterior
      cervical discectomy and fusion (ACDF) using different titanium interbody cages.
      The description of the clinical presentation, magnetic resonance imaging (MRI)
      appearances and management strategy are discussed. Both cases showed chronic neck
      pain and radiating pain from the shoulder to the arm. They had a history of
      blurry vision, cluster head ache, weakness, and numbness on the shoulder for 2
      years. MRI revealed multiple herniated discs between C4-7 and accompanied by the
      spur formation leading to the narrowness of the spinal canal and its foramina
      bilaterally. ACDF were performed and complete decompression of the spinal canal
      and its foramina were carried out. Twin M-cages (Ammtec Inc.-Japan) were placed
      in the first case at C5-7 levels and single cage of Smith Robinson (SR) was
      placed in the second case at C5-6 levels. There were no more blurry vision,
      cluster headache, weakness, and numbness, immediately after surgery. To our
      knowledge, this is the first reported cases of ACDF, using twin M-cages and
      single SR cage in Indonesia, with improvement immediately after surgery. Cervical
      spondylosis can present with cervicobrachialgia and radiculopathy and surgical
      treatment produces good functional outcome.

PMID- 27695568
TI  - Papillary tumor of pineal region: A rare entity.
AB  - Pineal tumors comprise 0.4 - 1.0% of intracranial space-occupying lesions in
      adults. Papillary tumor of pineal region (PTPR) is a very rare entity. It has
      been newly described in WHO 2007 classification of brain tumors. Only a few case
      reports are available in the literature. We report a case of a 60 year-old female
      presenting with headache, giddiness and reduced vision. Imaging studies showed a
      pineal mass with areas of hemorrhage. All ventricles were normal. There was a
      past history of a pineal gland tumor excised 2 years ago. This case is being
      reported for its rarity and aggressiveness in the form of recurrence.
      Limited/available immunohistochemistry workup has been done.

PMID- 27695569
TI  - Nocardia farcinica abscess of the cerebellum in an immunocompetent patient: A
      case report and review of the literature.
AB  - Nocardial brain abscesses are uncommon and rarely occur in patients without
      predisposing factors. They may be mistaken for gliomas or necrotic metastases,
      and surgical intervention may be required to make the diagnosis. We report the
      first case of Nocardia farcinica cerebellar abscess in a patient without
      immunosuppression. He presented to us with headache and instability beginning a
      week before. Brain magnetic resonance imaging (MRI) revealed a cystic lesion
      located at the right cerebellar hemisphere, hypointense in T1 and hyperintense in
      T2, with a fine wall that enhanced after injection of gadolinium. Image tests
      also showed a cavitated lesion at the upper lobule of the right lung. The patient
      underwent craniotomy and drainage of the cerebellar abscess. Initial post
      operative treatment with linezolid produced a limited response. He was re
      operated and vancomycin, imipenem and ciprofloxacin were added with an excellent
      outcome of the cerebellar and lung lesions.

PMID- 27695570
TI  - Ganglioglioma of conus medullaris in a patient of neurofibromatosis type 1: A
      novel association?
AB  - Ganglioglioma of the conus region is quite rare with only 12 reported cases.
      Ganglioglioma shares biologic features with neurofibromatosis leading to
      suggestions that the co-existence of the two diseases may be more than
      coincidental. We report a case of ganglioglioma of the conus medullaris in a
      patient of neurofibromatosis and explore the possible association of the two
      diseases.

PMID- 27695571
TI  - Resolution of aspergillosis in neuroimaging of an immunocompromised patient with
      pulmonary and cerebral lesions.
AB  - Central nervous system (CNS) aspergillosis is uncommon and considered the most
      lethal form of aspergillosis. Indeed, current therapeutic strategies such as
      combination antifungal regimen, neurosurgical resection of infected tissue, and
      removal of infection source fail to improve the unsatisfactory prognosis of CNS
      aspergillosis in the majority of the patients. The authors describe a case of
      chronic pulmonary aspergillosis with concomitant CNS lesions that dramatically
      responded to antifungal therapy and the CNS lesions resolved in follow-up
      imaging.

PMID- 27695572
TI  - Solid cystic trigeminal schwannoma with intraorbital extension causing proptosis
      and vision loss.
AB  - Schwannomas are slowly growing, well capsulated, benign tumors. Involvement of
      vestibular nerve is most commonly followed by trigeminal nerve. Trigeminal
      schwannoma is rare entity, and cystic degeneration with intraorbital extension of
      trigeminal schwannoma is even rarer. These tumors occur in fourth and fifth
      decades of life and patients have variable presentation depending on which
      cranial compartment is involved. Orbital schwannoma usually presents with
      proptosis with or without vision loss. We are reporting such a rare case of solid
      cystic trigeminal schwannoma with intraorbital extension through superior orbital
      fissure that was removed surgically.

PMID- 27695573
TI  - Traumatic bilateral basal ganglia bleed: A report of rare two cases and review of
      the literature.
AB  - Traumatic basal ganglia hemorrhage (TBGH) is relatively uncommon. Bilateral basal
      ganglia hematoma after trauma is extremely rare and is limited to case reports.
      We report two cases of traumatic bilateral basal ganglia hemorrhage and review
      the literature in brief. Both cases were managed conservatively. The general
      incidence of TBGH is reported between 2.4% and 3% of closed head injury. However,
      the incidence is higher in postmortem studies (9.8%). Bilateral traumatic basal
      ganglia hematoma is extremely rare. Descriptions are limited to case reports.

PMID- 27695574
TI  - Primary central nervous system teratoma with sarcomatous transformation in a
      young girl: Report of a rare case.
AB  - A 13-year-old girl presented with chief complaints of severe headache and
      vomiting followed by hemiparesis. Radiological examination suggested a space
      occupying lesion in the right parietal lobe. Craniotomy and debulking of the
      tumor mass were done. Histopathological and subsequent immunohistochemical
      examination showed a tumor composed of fascicle of atypical spindle cells which
      revealed reactivity to vimentin with interspersed areas of well-differentiated
      cartilage tissue. Hence, the diagnosis of teratoma with sarcomatous
      transformation was given. Detailed discussion including review of literature has
      been made regarding different aspect of the tumor.

PMID- 27695575
TI  - Peripheral nerve lipoma: Case report of an intraneural lipoma of the median nerve
      and literature review.
AB  - Adipose lesions rarely affect the peripheral nerves. This can occur in two
      different ways: Direct compression by an extraneural lipoma, or by a lipoma
      originated from the adipose cells located inside the nerve. Since its first
      description, many terms have been used in the literature to mention intraneural
      lipomatous lesions. In this article, the authors report a case of a 62-year-old
      female who presented with an intraneural median nerve lipoma and review the
      literature concerning the classification of adipose lesions of the nerve,
      radiological diagnosis and treatment.

PMID- 27695576
TI  - Anal extrusion of migrated ventriculo-peritoneal shunt catheter: An unusual
      complication and review of literature.
AB  - Authors present an unusual case of anal extrusion of peritoneal end of ventriculo
      peritoneal shunt in a 2-year-old male child. Pertinent literature is reviewed
      regarding this rare complication of a very commonly performed neurosurgical
      procedure.

PMID- 27695577
TI  - Malignancies Trends in a Hispanic Cohort of HIV Persons in Puerto Rico before and
      after cART.
AB  - BACKGROUND: The study describes the cancer trends in a Puerto Rican Hispanic
      HIV/AIDS cohort for three different time periods as defined by the availability
      of combination antiretroviral therapy (cART) in the Island: pre (1992-1995),
      early (1996-2002, and recent (2003-2009). METHODS: AIDS and non-AIDS related
      malignancies risk, standardized incidence rate and one year mortality was
      evaluated in the cohort before and after cART. RESULTS: Of the 281 malignancies
      found in 265 persons; 72% were in men, 38% in injecting drug users and 42.3% were
      AIDS related cancers. AIDS related cancer standardized incidence rates decreased
      significantly in the cART eras; however, Kaposi's sarcoma and invasive cervical
      carcinoma incidence remained significantly higher in the cohort when compare to
      the general population. On the contrary, non-AIDS related cancer standardized
      incidence rates increased significantly in the cART eras, specifically those of
      the oral/cavity/pharynx, liver, anus, vaginal, and Hodgkin's and non-Hodgkin's
      Lymphomas. Around 50% of the persons with cancers were reported dead within the
      first year of their diagnoses without a significant variation during the cART
      eras. CONCLUSION: The higher incidence of Kaposi's sarcoma, invasive cervical
      carcinoma and non-AIDS related malignancies and their high mortality in the cART
      eras is suggestive of the role of oncogenic viruses, environmental agents, risky
      lifestyle behaviors and inadequate cancer prevention efforts that contribute and
      accelerate the risk of malignant transformation in these subjects. Aggressive
      intervention in the form of vaccines, risky practice reduction, early screening,
      early treatment and adequate risk reduction education needs to be incremented in
      this vulnerable population.

PMID- 27695578
TI  - Power and Effective Study Size in Heritability Studies.
AB  - Correlation between study units in quantitative genetics studies often makes it
      difficult to compare important inferential aspects of studies. Describing the
      relatedness between study units is critical to capture features of pedigree
      studies involving heritability, including power and precision of heritability
      estimates. Blangero et al (2012) showed that in pedigree studies the power to
      detect heritability is a function of the true heritability and the eigenvalues of
      the kinship matrix. We extend this to a more general setting which allows
      statements about expected precision of heritability estimates. Using two
      different Taylor series approximations, we summarize the relatedness in a study
      design by one or two parameters. These relatedness summary parameters (RSPs) are
      functions of the eigenvalues or log-eigenvalues of the kinship matrix. Using the
      RSPs based on the log-eigenvalues, we accurately approximate the expectation of
      the likelihood ratio test and expected confidence interval widths. We define an
      effective sample size of a target study as one which has the equivalent power and
      precision to a reference design. Using unrelated sibpairs as the reference design
      provides very accurate assessments of power. RSPs and effective sample sizes
      provide new tools for comparing studies and communicating information about
      relatedness in heritability studies.

PMID- 27695579
TI  - Variations in Sexual Identity Milestones among Lesbians, Gay Men and Bisexuals.
AB  - Despite a large body of literature covering sexual identity development
      milestones, we know little about differences or similarities in patterns of
      identity development among subgroups of the lesbian, gay, and bisexual (LGB)
      population. For this study, we assessed identity milestones for 396 LGB New
      Yorkers, ages 18-59. Sexual identity and disclosure milestones, were measured
      across gender, sexual identity, race/ethnicity, and age cohort subgroups of the
      LGB sample. Men experienced most sexual identity milestones earlier than women,
      but they tended to take more time between milestones. LGBs in younger age cohorts
      experienced sexual identity milestones and disclosure milestones earlier than the
      older cohorts. Bisexual people experienced sexual identity and disclosure
      milestones later than gay and lesbian people. Timing of coming out milestones did
      not differ by race/ethnicity. By comparing differences within subpopulations, the
      results of this study help build understanding of the varied identity development
      experiences of people who are often referred to collectively as "the LGB
      community." LGB people face unique health and social challenges; a more complete
      understanding of variations among LGB people allows health professionals and
      social service providers to provide services that better fit the needs of LGB
      communities.

PMID- 27695581
TI  - Survival after partial and radical nephrectomy for high-risk disease: A
      propensity-matched comparison.
AB  - INTRODUCTION: Increasingly, partial nephrectomy has been applied to high-risk
      disease without evidence that its survival benefits can be extrapolated to this
      entity. We aimed to compare overall survival after partial vs. radical
      nephrectomy in patients with high-risk renal cell carcinoma. METHODS: Using the
      National Cancer Data Base, we identified patients who underwent partial or
      radical nephrectomy for high-risk disease between 2003 and 2006. High-risk
      disease was defined as the presence of adverse pathological features within the
      primary tumour, namely high-grade or unfavourable histology, T3 stage, or both.
      After matching the partial and radical nephrectomy groups based on propensity
      scores, 1680, 276, and 76 patients with high-grade or unfavourable histology, T3
      stage, or both adverse pathologic features, respectively, were available for
      analysis. Five-year overall survival was compared after partial vs. radical
      nephrectomy for each high-risk cohort using the Kaplan-Meier and log rank tests.
      RESULTS: Partial nephrectomy was associated with a statistically significant
      improvement in five-year overall survival compared to radical nephrectomy for
      small tumours (median size 3.0 cm; interquartile range 2.1-4.5 cm) with high
      grade or unfavourable histology (87% vs. 81%; p<0.01) or with pT3a stage (82% vs.
      71%; p<0.01). For patients concomitantly harbouring both adverse pathologic
      features, no difference in survival was detected (p=0.21). CONCLUSIONS: Partial
      nephrectomy is associated with survival benefits in patients with adverse
      pathologic features, suggesting that renal preservation is not only safe, but
      also potentially beneficial for high-risk disease. Due to inherent selection bias
      associated with partial nephrectomy use, prospective validation of these findings
      is needed.

PMID- 27695580
TI  - Mechanisms of Individual Differences in Impulsive and Risky Choice in Rats.
AB  - Individual differences in impulsive and risky choice are key risk factors for a
      variety of maladaptive behaviors such as drug abuse, gambling, and obesity. In
      our rat model, ordered individual differences are stable across choice
      parameters, months of testing, and span a broad spectrum, suggesting that rats,
      like humans, exhibit trait-level impulsive and risky choice behaviors. In
      addition, impulsive and risky choices are highly correlated, suggesting a degree
      of correlation between these two traits. An examination of the underlying
      cognitive mechanisms has suggested an important role for timing processes in
      impulsive choice. In addition, in an examination of genetic factors in impulsive
      choice, the Lewis rat strain emerged as a possible animal model for studying
      disordered impulsive choice, with this strain demonstrating deficient delay
      processing. Early rearing environment also affected impulsive behaviors, with
      rearing in an enriched environment promoting adaptable and more self-controlled
      choices. The combined results with impulsive choice suggest an important role for
      timing and reward sensitivity in moderating impulsive behaviors. Relative reward
      valuation also affects risky choice, with manipulation of objective reward value
      (relative to an alternative reference point) resulting in loss chasing behaviors
      that predicted overall risky choice behaviors. The combined results are discussed
      in relation to domain-specific versus domain-general subjective reward valuation
      processes and the potential neural substrates of impulsive and risky choice.

PMID- 27695582
TI  - Urothelial-based reconstructive surgery for upper- and mid-ureteral defects: Long
      term results.
AB  - INTRODUCTION: Ureteral strictures can result in obstructive nephropathy and renal
      function deterioration. Surgical management of ureteral defects, especially in
      the proximal- and mid-ureter, is particularly challenging. Our purpose was to
      analyze the long-term outcomes of urothelial-based reconstructive surgery for
      upper- and mid-ureteral defects. METHODS: We conducted a retrospective analysis
      of a single tertiary centre's database, including 149 patients treated for
      ureteral defects between 2001 and 2011. Thirty-one patients (21%) underwent
      complex urothelial-based surgical repairs for upper- and mid-ureter defects.
      Patients' median age was 61 years. The mean length of the ureteral strictures was
      2.5 cm, located in upper-, mid-ureter, or in between in 19 (61%), 10 (32%), and
      two (6%) patients, respectively. All patients were treated with a primary
      urothelial-based repair. Median followup time was 26 months. The primary outcome
      of the study was the long-term preservation of renal function and lack of
      clinical obstruction. The secondary endpoint of the study was the assessment of
      the intra- and postoperative complication rates. RESULTS: Most of the lesions
      were benign (22, 71%), while nine strictures (29%) were malignant. Seven patients
      (23%) suffered from postoperative complications, five of which were infectious.
      The median pre- and postoperative calculated glomerular filtration rates were 66
      ml/min/1.72m2 and 64ml/min/1.72m2, respectively. Success rate was 84%, defined as
      lack of need for re-operation or kidney drainage at the last followup.
      CONCLUSIONS: Upper- and mid-ureteral defects present a complex pathology
      necessitating experienced reconstructive surgical skills. Our data suggest good
      long-term results for primary urothelial-based reconstructions for these
      pathologies.

PMID- 27695583
TI  - Prospective investigation of penile length with newborn male circumcision and
      second to fourth digit ratio.
AB  - INTRODUCTION: We prospectively investigated the relationship between newborn male
      circumcision (NMC) and second to fourth digit ratio with penile length. METHODS:
      As participants for our study, we identified already circumcised young patients
      who visited our hospital for urological treatment. The age at which the
      circumcision had been done was assessed. The patients' height and weight were
      measured. Second to fourth digit ratio was calculated by measuring the second and
      fourth digit lengths. The flaccid and erectile penile lengths were measured from
      the base of the penis to the tip of the glans in standing position. RESULTS: A
      total of 248 patients were included in our study. In univariate analysis, height,
      second to fourth digit ratio, flaccid penile length, and age of circumcision were
      associated with erectile penile length. Among these variables, second to fourth
      digit ratio, flaccid penile length, and age of circumcision were significant
      predictive factors for erectile penile length in multivariate analysis. The
      subjects were divided into two groups, including 72 patients in the NMC group and
      176 patients in the non-NMC group. No significant difference was found in height,
      weight, and second to fourth digit ratio between both groups. However, flaccid
      (p<0.001) and erectile (p=0.001) penile lengths were shorter in the NMC group
      than in the non-NMC group. CONCLUSIONS: Despite the small number of subjects,
      this study shows that NMC was associated with shorter penile length. Second to
      fourth digit ratio, flaccid penile length, and age of circumcision were also
      significant predictive factors for erectile penile length. Further multicentre
      studies with larger number of subjects and biochemical analyses are needed for
      potential clinical applicability.

PMID- 27695584
TI  - Metabolic syndrome in patients with prostate cancer undergoing intermittent
      androgen-deprivation therapy.
AB  - INTRODUCTION: The presence of metabolic syndrome in men with prostate cancer
      (PCa) undergoing androgen-deprivation therapy (ADT), especially intermittent
      type, has not been completely evaluated. The aim of this study is to evaluate
      metabolic syndrome in men with PCa undergoing intermittent ADT. METHODS: In this
      longitudinal study, we studied the prevalence of metabolic syndrome and its
      components in 190 patients who were undergoing intermittent ADT. The metabolic
      syndrome was defined according to the Adult Treatment Panel III criteria. All
      metabolic parameters, including lipid profile, blood glucose, blood pressures,
      and waist circumferences of the patients were measured six and 12 months after
      treatment. RESULTS: Mean age of the patients was 67.5 +/- 6.74 years. The
      incidence of metabolic syndrome after six and 12 months was 6.8% and 14.7%,
      respectively. Analysis of various components of the metabolic syndrome revealed
      that patients had significantly higher overall prevalence of hyperglycemia,
      abdominal obesity, and hypertriglyceridemia in their six- and 12-month followups,
      but blood pressure has not been changed in the same period except for diastolic
      blood pressure after six months. CONCLUSIONS: Although there was an increased
      risk of metabolic syndrome in patients receiving intermittent ADT, it was lower
      than other studies that treated the same patients with continuous ADT. Also it
      seems that intermittent ADT has less metabolic complications than continuous ADT
      and could be used as a safe alternative in patients with advanced and metastatic
      PCa.

PMID- 27695585
TI  - Initial response of renal cell carcinoma to vemurafenib in a patient treated for
      metastatic melanoma.

PMID- 27695586
TI  - Ovarian vein thrombosis: A complication of percutaneous nephrolithotomy.
AB  - The medical and surgical complications of percutaneous nephrolithotomy (PCNL) are
      well-known, including deep venous thrombosis. Ovarian vein thrombosis (OVT) is a
      rare, but potentially serious type of venous thrombosis that has not previously
      been reported as a complication of PCNL or ureteral stent placement. We report a
      case of OVT associated with ureteral stenting following a tubeless PCNL. This
      complication was successfully managed conservatively without any short- or long
      term sequelae.

PMID- 27695587
TI  - Concurrent use of endourological and radiologic methods in the management of high
      grade renal trauma.
AB  - This case report explores the efficacy of simultaneous use of endourological and
      radiological methods to assess and manage high-grade renal trauma. A male rugby
      player was diagnosed with Grade 4 blunt renal trauma. A segment of the patient's
      kidney was isolated from the main renal pelvis with intact perfusion. This
      resulted in urinary extravasation. Ureteral stenting and angioembolization were
      used to treat the patient's severe symptoms. Angioembolization ablated functional
      tissue that was causing a persistent urinary leak. Following the treatment, the
      patient was discharged with no significant bleeding or leakage from the kidney.
      This report illustrates an uncommon use of this combined approach. Followup 18
      months post-trauma revealed normal blood pressure and approximately 30% loss of
      volume of the affected kidney.

PMID- 27695588
TI  - Multidisciplinary approach to giant paratesticular liposarcoma.
AB  - Primary paratesticular tumours are very rare and the spermatic cord (SCT) is the
      most frequent site of origin, with 20% of malignancy. Although liposarcoma is the
      most frequent histotype (46.6 %), less than 200 cases have been reported in the
      literature. We report the case of a 56-year-old man who presented a giant scrotal
      mass of 25 years of evolution and measuring 40 * 40 cm. It could be considered
      the greatest paratesticular liposarcoma described to date. Computed tomogaphy
      (CT) revealed mass features consistent with liposarcoma and the simultaneous
      presence of bilateral inguinal hernia with bladder involvement. A
      multidisciplinary approach was taken to remove the mass, solve the hernia, and
      provide functional results.

PMID- 27695589
TI  - Ectopic Cushing's syndrome due to retroperitoneal ACTH-producing paragangliomas.
AB  - Extra-adrenal pheochromocytomas, or paragangliomas, are rare tumours that derive
      from extra-adrenal chromaffin cells. Cushing's syndrome (CS) caused by
      paragangliomas is extremely rare. We report a 53-year-old man with hypertension,
      diabetes, and symptoms of hypokalemia. Computer tomography (CT) revealed two
      retroperitoneal masses and bilateral adrenal hyperplasia. Together with the
      laboratory examinations, ectopic CS caused by multiple paragangliomas was highly
      suspected. The patient underwent resections of retroperitoneal tumours, left
      kidney, and left adrenal; postoperative histopathology confirmed two
      paragangliomas that were both positively stained for adrenocorticotropic hormone
      (ACTH). He got clinical and biochemical recoveries without any recurrent evidence
      at the nine-month followup.

PMID- 27695590
TI  - Isolated thrombosis of right spermatic vein with underlying Factor V Leiden
      mutation.
AB  - Spermatic vein thrombosis is a very uncommon clinical entity. Most cases involve
      the left side. Herein, we present an unusual case of a young man who presented
      with spermatic vein thrombosis on the right side with an underlying Factor V
      Leiden mutation. To our knowledge, it is the first case in the literature.

PMID- 27695591
TI  - Correction in supplement data.
AB  - [This corrects the article on p. S144 in vol. 10.].

PMID- 27695592
TI  - The Western snip, stitch, and tug hydrocelectomy: How I do it.
AB  - INTRODUCTION: Adult idiopathic hydrocele is a common benign disorder that merits
      surgical correction when symptomatic. The most popular techniques for repair are
      plication (Lord's procedure) or excision and eversion of the tunica vaginalis
      (Jaboulay procedure). Established complications from these traditional repairs
      include hematoma, recurrence, and infection. These procedures are performed
      through a scrotal incision. We describe a novel technique of hydrocele repair
      with gubernaculum preservation through a subinguinal incision. METHODS: The novel
      technique is described in detail. A retrospective review was performed of those
      patients treated by a single surgeon with the subinguinal technique. Demographic
      information, indication for treatment, success rate, and details regarding
      complications were collected. RESULTS: We term the technique the "Snip, Stitch &
      Tug" repair. Through a small subinguinal incision, the tunica is everted
      posterior to the spermatic cord and testis without resection of the hydrocele sac
      or division of the gubernaculum. Twelve patients with postoperative followup were
      identified. Eleven patients (92%) treated with the novel technique were cured.
      There was only one complication (superficial wound infection) recorded after this
      technique. CONCLUSIONS: Idiopathic hydrocele repair with gubernaculum
      preservation can be easily and safely performed through a small subinguinal
      incision.

PMID- 27695593
TI  - Statistical methods and computing for big data.
AB  - Big data are data on a massive scale in terms of volume, intensity, and
      complexity that exceed the capacity of standard analytic tools. They present
      opportunities as well as challenges to statisticians. The role of computational
      statisticians in scientific discovery from big data analyses has been under
      recognized even by peer statisticians. This article summarizes recent
      methodological and software developments in statistics that address the big data
      challenges. Methodologies are grouped into three classes: subsampling-based,
      divide and conquer, and online updating for stream data. As a new contribution,
      the online updating approach is extended to variable selection with commonly used
      criteria, and their performances are assessed in a simulation study with stream
      data. Software packages are summarized with focuses on the open source R and R
      packages, covering recent tools that help break the barriers of computer memory
      and computing power. Some of the tools are illustrated in a case study with a
      logistic regression for the chance of airline delay.

PMID- 27695594
TI  - Predictors of Prolonged Hospital Stay in Status Migrainosus.
AB  - BACKGROUND: Patients with status migrainosus often need to be admitted due to the
      severity of their headaches. Their hospitalization is often prolonged due to poor
      headache control. Large sample studies looking into the factors associated with
      prolonged length of stay (pLOS) in status migrainosus are lacking. METHODS: We
      utilized the Nationwide Inpatient Sample database to identify 4325 patients with
      primary discharge diagnosis of status migrainosus. Length of inpatient stay (LOS)
      of more than 6 days (90th percentile of LOS) was defined as pLOS. Patient
      demographics, hospital characteristics, mood disorders, anxiety disorder, and
      common medical comorbidities were identified. Multivariable logistic regression
      was used to identify factors associated with pLOS. RESULTS: We found 402 patients
      with pLOS. Female gender, African American race, mood disorder, obesity, opioid
      abuse, congestive heart failure, and chronic renal failure were significant
      independent predictors of pLOS. Median inflation-adjusted cost of hospitalization
      was USD$3829 (interquartile range: 2419-5809). CONCLUSION: We were able to
      identify several factors associated with pLOS in status migrainosus. Most of the
      factors we found were similar to those known to increase the prevalence and
      severity of migraine in the general population. Knowledge of these factors may
      help physicians identify high-risk patients to institute early migraine abortive
      and prophylactic treatment in order to shorten the length of hospital stay.

PMID- 27695595
TI  - International Classification of Diseases, Ninth Revision (ICD-9) Diagnosis Codes
      Can Identify Cerebral Venous Thrombosis in Hospitalized Adults.
AB  - BACKGROUND: Cerebral venous thrombosis (CVT) is a relatively rare and
      understudied disease. We sought to determine the accuracy of International
      Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes to identify
      CVT. METHODS: Retrospective chart review using the electronic medical record
      (EMR) to identify all patients discharged with CVT following admission or
      emergency department visit from May 1, 2010 to May 1, 2015 at our center.
      RESULTS: We identified 111 patients with an ICD-9 discharge diagnosis code of
      325.0 (cerebral sinovenous thrombosis, excluding nonpyogenic cases and cases
      associated with pregnancy and the puerperium), 437.6 (CVT of nonpyogenic origin),
      or 671.5 (CVT complicating pregnancy, childbirth, or the puerperium) in any
      position. Of these 111 patients, 84 (75.7%) had confirmed CVT after EMR review.
      Searching outpatient and radiology records, we found an additional 24 patients
      with CVT who were not identified via query of ICD-9 discharge diagnosis codes.
      The ICD-9 codes 325.0, 437.6, or 671.5 in any position had a combined sensitivity
      of 77.8% and specificity of 92.7%; in the primary position, they had a
      sensitivity of 28.7% and specificity of 98.3%. CONCLUSION: The ICD-9 codes 325.0,
      437.6, and 671.5 can be used to identify CVT with acceptable sensitivity and
      specificity.

PMID- 27695596
TI  - Ziprasidone as a Potential Abortive Therapy for Status Migrainosus.
AB  - Migraine headache is among the most prevalent neurologic disorders. Status
      migrainosus often leads to hospitalization, and multiple medications are
      sometimes required for symptomatic relief. In 2008, neurologists at our
      institution started using the atypical antipsychotic ziprasidone as an abortive
      medication for status migrainosus. The Clinical Investigation Data Exploration
      Repository was used to search for patients admitted to the Barnes-Jewish Hospital
      inpatient neurology service with diagnoses of "headache" or "migraine." Patients
      were identified as having status migrainosus if they met the International
      Headache Society criteria for a migraine lasting >72 hours. Clinical records of
      identified patients were then entered into a secure online database (REDCap).
      Between 2008 and 2015, a total of 34 patients received 10 to 40 mg of ziprasidone
      for the treatment of status migrainosus. Among patients who received ziprasidone,
      headache severity decreased 5.68 +/- 3.0 points on a 10-point scale, from
      admission to discharge. Ziprasidone was the last abortive medication added prior
      to discharge in 65% of cases. The 30-day readmission rate for migraine headache
      in patients who received ziprasidone was 12%. Ziprasidone was well tolerated,
      with side effects limited to a mild dystonic reaction (n = 1), rhinorrhea (n =
      1), and a prolonged QTc of 495 milliseconds (n = 1). This observational study
      suggests that ziprasidone may be a safe, effective abortive medication for the
      treatment of status migrainosus. Further studies comparing ziprasidone to
      standard of care are warranted.

PMID- 27695597
TI  - Continuous Qualitative Electroencephalography as a Noninvasive Neuromonitor.
AB  - Intracranial pressure (ICP) monitoring frequently guides key decisions in the
      management of diseases causing intracranial hypertension. Although typically
      measured by invasive means, contraindications may leave the clinician with little
      recourse for dynamic ICP evaluation-particularly when the patient's mental status
      is compromised. We describe here a healthy 18-year-old woman who subacutely
      progressed to coma due to diffuse cerebral venous sinus thrombosis.
      Heparinization precluded the use of invasive ICP monitoring, and
      electroencephalography (EEG) was used novelly as a surrogate ICP monitor. She
      responded well to anticoagulation and hyperosmolar therapy guided by qualitative
      EEG and was later discharged with a nearly normal neurologic examination. She was
      found to have Salmonella bacteremia, heterozygous prothrombin and factor V Leiden
      mutations, and hemoglobin H disease.

PMID- 27695598
TI  - Electrographic Correlates of Plateau Waves in Patients With Leptomeningeal
      Metastases.
AB  - We describe video electroencephalography (video-EEG) correlates of transient
      neurological attacks due to plateau waves-paroxysmal elevations in intracranial
      pressure-in patients with leptomeningeal metastases. We identified 3 patients
      with leptomeningeal metastases, intracranial hypertension, and transient
      neurological attacks captured on video-EEG without evidence of seizures or
      epileptiform activity. We identified all clinical events on video and reviewed
      the corresponding EEG data for evidence of abnormalities. All 3 patients had mild
      to moderate slowing and 2 had frontal intermittent rhythmic delta activity during
      background EEG recording. There were 33 clinical events recorded and stereotyped
      for each patient. All 33 events were associated with an increase in delta range
      slowing of >=30% compared to the background. This abnormality started <=2 minutes
      before the onset of clinical symptoms and persisted for minutes after clinical
      resolution. This study is the first to carefully describe the electrographic
      correlates of transient neurological attacks due to plateau waves in patients
      with leptomeningeal metastasis. Clinical attacks were consistently associated
      with a possible EEG signature of diffuse delta range slowing. Future studies can
      validate the sensitivity and specificity of these EEG changes as a prognostic
      and/or response biomarker in patients with leptomeningeal metastases with or
      without intracranial hypertension.

PMID- 27695599
TI  - Cefepime-Associated SIRPIDs in a Patient With Normal Renal Function.
AB  - Cefepime has been associated with encephalopathy and with nonconvulsive seizure
      activity, primarily in patients with renal impairment. Here, we report a case of
      cefepime-associated encephalopathy in a patient with normal renal function with
      stimulus-induced rhythmic activity seen on electroencephalogram, which resolved
      on discontinuation of cefepime. We bring this to the attention of the
      neurohospitalist community, as cefepime is widely used in the hospital setting,
      and cefepime-related neurotoxicity may go overlooked, especially in patients with
      normal renal function. Neurologists must recognize drug-related patterns, as the
      treatment is removing a medication rather than adding an antiepileptic
      medication.

PMID- 27695600
TI  - Human African Trypanosomiasis Encephalitis in the United States: Serial Magnetic
      Resonance Imaging.
AB  - It is important to recognize the signs and symptoms of human African
      trypanosomiasis (HAT) in order to facilitate early diagnosis and treatment. A 36
      year-old man developed encephalitis caused by HAT. This encephalitis can appear
      many years after well-tolerated systemic infection. The neurologic manifestations
      developed 7 years after he had emigrated from Cameroon to the United States. We
      demonstrate the magnetic resonance imaging before, during, and after his
      treatment with intravenous eflornithine. Clinical signs and symptoms of HAT can
      be nonspecific and precede abnormalities on magnetic resonance imaging. Human
      African trypanosomiasis should be considered in the differential diagnosis of
      patients who have lived in sub-Saharan Africa and have a clinical presentation of
      subacute encephalitis.

PMID- 27695601
TI  - A 27-Year-Old Man With Right-Sided Hemiparesis and Dysarthria.

PMID- 27695602
TI  - A Case Study in the History of Neurology.
AB  - We review the case of a young man who developed a constellation of symptoms and
      signs-bizarre behavior, seizures, abnormal movements, and autonomic instability
      that evaded diagnosis at the time of presentation. We use this case to explore
      the way medical knowledge changes over time. Despite the dramatic advances in our
      understanding of neurological diseases in recent decades, physicians tend to
      approach diseases and diagnoses as if they were immutable. Our case reinforces
      how the diagnosis and treatment of disease are determined by an ever-changing
      historical context driven by the rapid expansion of medical knowledge. We discuss
      the implications of this realization and present strategies for navigating the
      boundaries of knowledge, both in practice and in principle.

PMID- 27695603
TI  - INTENSITY INHOMOGENEITY CORRECTION OF MACULAR OCT USING N3 AND RETINAL FLATSPACE.
AB  - As optical coherence tomography (OCT) has increasingly become a standard modality
      for imaging the retina, automated algorithms for processing OCT data have become
      necessary to do large scale studies looking for changes in specific layers. To
      provide accurate results, many of these algorithms rely on the consistency of
      layer intensities within a scan. Unfortunately, OCT data often exhibits
      inhomogeneity in a given layer's intensities, both within and between images.
      This problem negatively affects the performance of segmentation algorithms and
      little prior work has been done to correct this data. In this work, we adapt the
      N3 framework for intensity inhomogeneity correction, which was originally
      developed to correct MRI data, to work for macular OCT data. We first transform
      the data to a flattened macular space to create a template intensity profile for
      each layer giving us an accurate initial estimate of the gain field. N3 will then
      produce a smoothly varying field to correct the data. We show that our method is
      able to both accurately recover synthetically generated gain fields and improves
      the stability of the layer intensities.

PMID- 27695604
TI  - "I need to hear from women who have 'been there'": Developing a woman-focused
      intervention for drug use and partner violence in the emergency department.
AB  - OBJECTIVE: Addressing violence and linking women to community services in
      parallel with drug change goals is critical for women with coexisting intimate
      partner violence (IPV) and substance use disorders (SUD). Our objective was to
      develop a Web-based intervention to address violence and drug use among women
      patients in the ED. METHODS: The intervention was developed in a five-step
      process: 1) Initial intervention development based on selected theoretical
      frameworks; 2) In-depth interviews with the target population; 3) Intervention
      adaptation, with iterative feedback from further interviews; 4) Beta testing and
      review by an advisory committee of domestic violence advocates; 5) Acceptability
      and feasibility testing in a small open trial. RESULTS: Themes supported the
      selection of MI and empowerment models but also guided major adaptations to the
      intervention, including the introduction of videos and a more robust booster
      phone call. Participants in the open trial reported high scores for satisfaction,
      usability, and consistency with essential elements of motivational interviewing.
      CONCLUSIONS: This qualitative work with our target population of women in the ED
      with SUD experiencing IPV underscored the importance of connection to peers and
      empathetic human contact. We developed an acceptable and feasible intervention
      distinct from prior ED-based brief interventions for substance-using populations.

PMID- 27695606
TI  - A price comparison of recently launched proprietary pharmaceuticals in the UK and
      the US.
AB  - OBJECTIVE: To explore the relationship between prices charged by manufacturers of
      proprietary pharmaceuticals in the US and in the UK in recent years (2013-2016),
      expressed as a multiplier, and to detail to what extent this relationship differs
      for high-cost therapies used in smaller patient populations, as compared to lower
      cost drugs. METHODOLOGY: Therapies assessed by the Scottish Medicines Consortium
      (SMC) in the UK between 1 January 2013 and 1 June 2016 were identified; only in
      patent therapies were included in the analysis (to avoid the impact of price
      erosion post patent expiry); results were grouped according to annual cost per
      patient (whether considered high-cost, i.e., >L2,500 per patient per year, or
      not) and the size of the UK target population [whether considered orphan (<32,000
      patients per year), ultra-orphan (<1,000 patients per year), or not]. Publicly
      listed prices were obtained in the US and UK and were adjusted where necessary to
      estimate the prices charged by manufacturers in the respective countries. The
      difference in price (per unit of the same strength and formulation) was
      calculated as a multiplier between the US and UK prices for each of the therapies
      identified. RESULTS: Based on the methodological approach described, 88 therapies
      were identified and included in the analysis. The multiplier between the US and
      UK prices was 3.64 for therapies with an estimated annual cost <L2,500; this was
      reduced to 1.90 for higher-cost therapies. A downward trend was also evident in
      the subgroup analysis of the higher-cost therapies; as the estimated target
      patient populations reduced from >32,000 down to <1,000, the US/UK price
      multipliers reduced from 2.13 for the former to 1.48 for the latter. CONCLUSION:
      Although pharmaceutical prices have been found to be on average substantially
      higher in the US compared to the UK, our findings suggest that this price
      discrepancy is smaller for higher-cost therapies targeting small patient
      populations. Manufacturers of high-cost products should therefore factor this in
      when formulating pricing strategies because the potential for higher pricing in
      the US seems greater for primary care products targeting large patient
      populations.

PMID- 27695605
TI  - Outcome of Adult Brain Tumor Consortium (ABTC) prospective dose-finding trials of
      I-125 balloon brachytherapy in high-grade gliomas: challenges in clinical trial
      design and technology development when MRI treatment effect and recurrence appear
      similar.
AB  - OBJECTIVES: The aim of this study is to define the maximal safe radiation dose to
      guide further study of the GliaSite balloon brachytherapy (GSBT) system in
      untreated newly diagnosed glioblastoma (NEW-GBM) and recurrent high-grade glioma
      (REC-HGG). GBST is a balloon placed in the resection cavity and later filled
      through a subcutaneous port with liquid I-125 Iotrex, providing radiation doses
      that diminish uniformly with distance from the balloon surface. METHODS: The
      Adult Brain Tumor Consortium initiated prospective dose-finding studies to
      determine maximum tolerated dose in NEW-GBM treated before standard RT or after
      surgery for REC-HGG. Patients were inevaluable if there was progression before
      the 90-day posttreatment toxicity evaluation point. RESULTS: Ten NEW-GBM patients
      had the balloon placed, and 2/10 reached the 90 day timepoint. Five REC-HGG
      enrolled and two were assessable at the 90-day evaluation endpoint. Imaging
      progression occurred before 90-day evaluation in 7/12 treated patients. The
      trials were closed as too few patients were assessable to allow dose escalation,
      although no dose-limiting toxicities (DLTs) were observed. Median survival from
      treatment was 15.3 months (95 % CI 7.1-23.6) for NEW-GBM and 12.8 months (95 % CI
      4.2-20.9) for REC-HGG. CONCLUSION: These trials failed to determine a maximum
      tolerated dose (MTD) for further testing as early imaging changes, presumed to be
      progression, were common and interfered with the assessment of treatment-related
      toxicity. The survival outcomes in these and other related studies, although
      based on small populations, suggest that GSBT may be worthy of further study
      using clinical and survival endpoints, rather than standard imaging results. The
      implications for local therapy development are discussed.

PMID- 27695607
TI  - Male Infertility during Antihypertensive Therapy: Are We Addressing Correctly The
      Problem?
AB  - Male fertility significantly decreased in the last 50 years, as showed in several
      studies reporting a reduction of sperm counts per ml in the seminal fluid.
      Several "acute" pharmacological treatments, as antibiotics, could cause
      subclinical and temporary reduction of male fertility; conversely, long-term
      medical treatment may severely affect male fertility, although this effect could
      be considered transient in most of the cases. Thus, nowadays, several long-term
      pharmacological treatments may represent a clinical challenge. The association
      between several kind of antihypertensive drugs and reduction of male fertility
      has been showed in the mouse model, although the modification(s) which may alter
      this fine-regulated machinery are still far to be elucidated. Furthermore, well
      designed observational studies and randomized controlled trials are needed to
      accurately define this association in human model, meaning a narrative overview
      synthesizing the findings of literature retrieved from searches of computerized
      databases. We strongly solicit future human studies (both observational and
      randomized clinical trials) on large cohorts with adequate statistical power
      which may clarify this possible association and the effects (reversible or
      permanent) of each drug. Furthermore, we suggest a close collaboration between
      general practitioners, cardiologists, and andrologists in order to choose the
      most appropriate antihypertensive therapy considering also patient's reproductive
      desire and possible risk for his fertility.

PMID- 27695608
TI  - Aromatase Inhibitors for Endometriosis-Associated Infertility; Do We Have
      Sufficient Evidence?
AB  - Orally active aromatase inhibitors (AIs) have gained attention for treatment of
      infertile women with endometriosis in whom aromatase p450 is aberrantly
      expressed. This review aimed to critically appraise and summarize the available
      evidence concerning the use of AIs for management of endometriosis-associated
      infertility. PubMed was searched to May 2015 with the following key words:
      endometriosis, infertility and aromatase. Priority was given for randomized
      controlled trials (RCTs) followed by other study designs. Main outcome measures
      were as follows: rates of clinical pregnancy, miscarriage and live birth as well
      as endocrine outcomes. Eighty-two abstracts were screened and six original
      articles were included. A RCT demonstrated that post-operative letrozole
      treatment did not improve spontaneous pregnancy rate. Another RCT reported no
      superiority of letrozole superovulation over clomiphene citrate (each combined
      with intrauterine insemination) in minimalmild endometriosis and previous
      laparoscopic treatment. Anastrozole significantly inhibited the growth of
      endometriotic cells and their estrogen production in culture. In assisted
      reproductive technology (ART) cycles, dual suppression (Agonist/anastrozole) was
      tested in a pilot study with a pregnancy rate of 45% however, high pregnancy loss
      (30%) occurred. A retrospective study showed that letrozole may improve
      endometrial receptivity in endometriotic patients undergoing in vitro
      fertilization (IVF). An opposite view from an in vitro study showed lower
      estradiol production and aromatase expression in cultured granulosa cells from
      endometriotic women undergoing IVF and marked reduction under letrozole. In
      conclusion, current evidence is limited. More trials are warranted to enhance our
      knowledge and provide a clear and unequivocal evidence to guide our clinical
      management of infertile women with endometriosis using AIs.

PMID- 27695609
TI  - Prevalence of Infertility Problems among Iranian Infertile Patients Referred to
      Royan Institute.
AB  - BACKGROUND: Few studies have been conducted on the infertility problems in Iran.
      This study aimed to investigate the prevalence of infertility problems and
      related factors in Iranian infertile patients. MATERIALS AND METHODS: In this
      cross sectional study, 405 infertile patients referred to Royan Institute,
      Tehran, Iran, between 2014 and 2015, were selected by simple random sampling.
      Participants completed the Fertility Problem Inventory (FPI) including 46
      questions in five domains (social concern, sexual concern, relationship concern,
      rejection of parenthood, and need for parenthood). Mean difference between male
      and female was verified using independent-samples Student's t test. A generalized
      linear model (GLM) was also used for testing the effect of variables on the
      fertility problems. Data was analyzed using Stata software version 13. RESULTS:
      The mean age (SD) of participants was 31.28 (5.42). Our results showed that 160
      infertile men (95.23%) were classified as very high prevalence of infertility
      problems. Among infertile women, 83 patients (35.02%) were as very high
      prevalence of infertility problems, and 154 patients (64.98%) were as high
      prevalence. Age (P<0.001), sex (P<0.001), a history of abortion (P=0.009),
      failure of previous treatment (P<0.001), and education (P=0.014) had a
      significant relationship with FPI scores. CONCLUSION: Bases on the results of
      current study, an younger male with lower education level, history of abortion
      and history of previous treatments failure experienced more infertility problems.

PMID- 27695610
TI  - Assisted Reproductive Technology in Iran: The First National Report on Centers,
      2011.
AB  - BACKGROUND: Due to the worldwide increase in infertility, it is both necessary
      and important to have assisted reproductive technology (ART) registries. In Iran,
      donation and surrogacy programs are approved by decrees from religious scholars.
      ART has been used since 1984 in Iran and the first Iranian infant conceived by
      gamete intra-fallopian transfer (GIFT) was born in 1989. This report, however, is
      the first national report on Iranian ART centers. MATERIALS AND METHODS: This
      cross-sectional study, conducted under the supervision of the Iranian Ministry of
      Health, presented a summary of the numbers and percentages of centers that
      provided infertility services in Iran, as well as the status of ART in Iran
      during 2011. RESULTS: A total of 52 centers reported treatment cycles and
      performed approximately 29000 intrauterine insemination (IUI), in addition to
      35000 in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI)
      cycles. CONCLUSION: Iran has considerable potential to provide IVF services for
      both Iranians as well as other nationalities throughout the region. This proves
      the need for a national center that will implement a registry system.

PMID- 27695611
TI  - Comparison of Quality of Life, Sexual Satisfaction and Marital Satisfaction
      between Fertile and Infertile Couples.
AB  - BACKGROUND: Fertility plays an important role in sexual and psychological
      function in families. Infertility can result in major emotional, social, and
      mental disorders, including a reduction in satisfaction with marital life and
      quality of life. The present study aimed to compare the quality of life and
      marital satisfaction and sexual satisfaction between fertile and infertile
      couples. MATERIALS AND METHODS: This analytical cross-sectional study was
      conducted on 250 couples at the Fatemiyeh Educational Research Center affiliated
      to Hamadan University of Medical Sciences, Hamadan, Iran, from May to August in
      2014. The subjects were randomly selected from the patients referred to this
      center using a table of random numbers. They were then allocated into two groups
      of infertile group (n=125) and fertile group (n=125). The study participants
      completed World Health Organization Quality of Life-BREF (WHOQOL-BREF)
      questionnaire, Linda Berg's Sexual Satisfaction Scale, and Enrich Marital
      Satisfaction Scale. Then, the data were entered into the SPSS version16 for
      statistical analysis. The Chi-square and Mann-Whitney tests were also applied to
      compare the data between the groups. RESULTS: The results revealed no significant
      difference between the two groups regarding demographic and general health
      variables. The mean scores of sexual satisfaction were 63.67 +/- 13.13 and 46.37
      +/- 7.72 in the fertile and infertile couples, respectively. Furthermore, the
      mean scores of marital satisfaction were also 44.03 +/- 9.36 and 36.20 +/- 4.03
      in the fertile and infertile groups, respectively. Our finding demonstrated that
      the fertile couples obtained significantly higher mean scores of quality of life
      as well as lower mean scores of sexual satisfaction and marital satisfaction as
      compared to the infertile ones (P<0.001). CONCLUSION: According to the results,
      the fertile couples obtained significantly higher quality of life and lower
      sexual satisfaction and marital satisfaction as compared to the infertile ones.
      Therefore, holding consultation programs and conducting more studies are
      necessary for improving the quality of life and promoting sexual and marital
      satisfaction in infertile couples.

PMID- 27695612
TI  - Cord Blood Karyotyping: A Safe and Non-Invasive Method for Postnatal Testing of
      Assisted Reproductive Technology Children.
AB  - BACKGROUND: To verify the hypothesis that the incidence of chromosomal
      abnormalities increases in babies conceived by different assisted reproduction
      procedures. The availability of the umbilical cord blood encouraged us to study
      this hypothesis via this method. MATERIALS AND METHODS: This is a descriptive
      study, umbilical cord blood samples of assisted reproductive technology (ART)
      children were analyzed with standard cytogenetic techniques (G banding).
      Karyotyping was possible in 109 cases. RESULTS: The number of abnormal cases was
      four (3.7%), among which, three cases (2.8%) were inherited and only 1 case
      (0.9%) was a de novo translocation. In total, the incidence of de novo
      chromosomal abnormalities was in the range observed in all live births in the
      general population (0.7-1%). CONCLUSION: No significant difference in the
      incidence of chromosomal abnormality was found between ART and naturally
      conceived babies. To date, several studies have examined the medical and
      developmental outcome of ART children and still have not reached a definite
      conclusion. Genetic counseling is recommended as an integral part of planning of
      treatment strategies for couples wishing to undergo ART.

PMID- 27695613
TI  - Mitochondrial Genetic Variation in Iranian Infertile Men with Varicocele.
AB  - BACKGROUND: Several recent studies have shown that mitochondrial DNA mutations
      lead to major disabilities and premature death in carriers. More than 150
      mutations in human mitochondrial DNA (mtDNA) genes have been associated with a
      wide spectrum of disorders. Varicocele, one of the causes of infertility in men
      wherein abnormal inflexion and distension of veins of the pampiniform plexus is
      observed within spermatic cord, can increase reactive oxygen species (ROS)
      production in semen and cause oxidative stress and sperm dysfunction in patients.
      Given that mitochondria are the source of ROS production in cells, the aim of
      this study was to scan nine mitochondrial genes (MT-COX2, MT-tRNALys , MT-ATP8,
      MT-ATP6, MT-COX3, MT-tRNAGly , MT-ND3, MT-tRNAArg and MT-ND4L) for mutations in
      infertile patients with varicocele. MATERIALS AND METHODS: In this cross
      sectional study, polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and DNA sequencing were used to detect and identify point
      mutations respectively in 9 mitochondrial genes in 72 infertile men with
      varicocele and 159 fertile men. In brief, the samples showing altered
      electrophoretic patterns of DNA in the SSCP gel were sent for DNA sequencing to
      identify the exact nucleotide variation. RESULTS: Ten type nucleotide variants
      were detected exclusively in mitochondrial DNA of infertile men. These include
      six novel nucleotide changes and four variants previously reported for other
      disorders. CONCLUSION: Mutations in mitochondrial genes may affect respiratory
      complexes in combination with environmental risk factors. Therefore these
      nucleotide variants probably lead to impaired ATP synthesis and mitochondrial
      function ultimately interfering with sperm motility and infertility.

PMID- 27695614
TI  - Expression Profile of Developmentally Important Genes in preand peri-Implantation
      Goat Embryos Produced In Vitro.
AB  - BACKGROUND: Little is understood about the regulation of gene expression during
      early goat embryo development. This study investigated the expression profile of
      19 genes, known to be critical for early embryo development in mouse and human,
      at five different stages of goat in vitro embryo development (oocyte, 8-16 cell,
      morula, day-7 blastocyst, and day 14 blastocyst). MATERIALS AND METHODS: In this
      experimental study, stage-specific profiling using real time-quantitative
      polymerase chain reaction (RT-qPCR) revealed robust and dynamic patterns of stage
      specific gene activity that fall into four major clusters depending on their
      respective mRNA profiles. RESULTS: The gradual pattern of reduction in the
      maternally stored transcripts without renewal thereafter (cluster-1: Lifr1,
      Bmpr1, Alk4, Id3, Ctnnb, Akt, Oct4, Rex1, Erk1, Smad1 and 5) implies that their
      protein products are essential during early cleavages when the goat embryo is
      silent and reliant to the maternal legacy of mRNA. The potential importance of
      transcription augment at day-3 (cluster-2: Fzd, c-Myc, Cdc25a, Sox2) or day- 14
      (cluster-3: Fgfr4, Nanog) suggests that they are nascent embryonic mRNAs which
      intimately involved in the overriding of MET or regulation of blastocyst
      formation, respectively. The observation of two expression peaks at both day-3
      and day-14 (cluster-4: Gata4, Cdx2) would imply their potential importance during
      these two critical stages of preand periimplantation development. CONCLUSION:
      Evolutionary comparison revealed that the selected subset of genes has been
      rewired in goat and human/goat similarity is greater than the mouse/goat or
      bovine/goat similarities. The developed profiles provide a resource for
      comprehensive understanding of goat preimplantation development and pluripotent
      stem cell engineering as well.

PMID- 27695615
TI  - Current developments in molecular monitoring in chronic myeloid leukemia.
AB  - Molecular monitoring plays an essential role in the clinical management of
      chronic myeloid leukemia (CML) patients, and now guides clinical decision making.
      Quantitative reverse-transcriptase-polymerase-chain-reaction (qRT-PCR) assessment
      of BCR-ABL1 transcript levels has become the standard of care protocol in CML.
      However, further developments are required to assess leukemic burden more
      efficiently, monitor minimal residual disease (MRD), detect mutations that drive
      resistance to tyrosine kinase inhibitor (TKI) therapy and identify predictors of
      response to TKI therapy. Cartridge-based BCR-ABL1 quantitation, digital PCR and
      next generation sequencing are examples of technologies which are currently being
      explored, evaluated and translated into the clinic. Here we review the emerging
      molecular methods/technologies currently being developed to advance molecular
      monitoring in CML.

PMID- 27695616
TI  - Recent advances and novel treatment paradigms in acute lymphocytic leukemia.
AB  - This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL)
      given the advances in the relapsed/refractory setting. The development of
      antibody treatments (including antibody drug conjugates with toxins) offers a
      different treatment approach compared with conventional chemotherapy regimens.
      Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as
      blinatumomab harness the cytotoxic activity of T cells against CD19-positive
      lymphoblasts. Another strategy involves the use of chimeric antigen receptor
      (CAR) T cells. CAR T cells have demonstrated promising results in the
      relapsed/refractory setting. However, the use of BiTEs and CAR T cells is also
      associated with a distinct set of adverse reactions that must be taken into
      account by the treating physician. Apart from the above strategies, the use of
      other targeted therapies has attracted interest. Namely, the discovery of the
      Philadelphia (Ph)-like signature in children and young adults with ALL has led to
      the use of tyrosine kinase inhibitors (TKI) in these patients. The different
      drugs and strategies that are being tested in the relapsed/refractory ALL setting
      pose a unique challenge in identifying the optimum sequence of treatment and
      determining which approaches should be considered for frontline treatment.

PMID- 27695617
TI  - The potential of venetoclax (ABT-199) in chronic lymphocytic leukemia.
AB  - Venetoclax (VEN, ABT-199/GDC-0199) is an orally bioavailable BH3-mimetic that
      specifically inhibits the anti-apoptotic B-cell lymphoma/leukemia 2 (BCL2)
      protein. Although BCL2 overexpression is not genetically driven in chronic
      lymphocytic leukemia (CLL), it is nearly universal and represents a highly
      important and prevalent mechanism of apoptosis evasion, making it an attractive
      therapeutic target. This review summarizes the role of BCL2 in CLL pathogenesis,
      the development path targeting its inhibition prior to VEN, and the preclinical
      and clinical data regarding the effectiveness and safety of VEN. We further
      strive to contextualize VEN in the current CLL treatment landscape and discuss
      potential mechanisms of resistance.

PMID- 27695618
TI  - Treatment of multiple myeloma with the immunostimulatory SLAMF7 antibody
      elotuzumab.
AB  - Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain
      of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in
      multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its
      cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody
      induced selective lysis of tumor cells by activated natural killer (NK) cells.
      Furthermore, elotuzumab has been shown to directly induce NK-cell activation by
      binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell
      function by promoting the secretion of cytokines from NK cells. In combination
      with lenalidomide and low-dose dexamethasone, elotuzumab has shown remarkable
      effects in patients with relapsed or refractory multiple myeloma. In these
      patients, the risk of disease progression or death was significantly reduced by
      30% on elotuzumab. Currently, elotuzumab is being evaluated in various myeloma
      patient populations and combination regimens. This review discusses the use of
      elotuzumab as an antimultiple myeloma agent and provides an update on the results
      of recent clinical trials evaluating the safety and efficacy of elotuzumab for
      the treatment of multiple myeloma.

PMID- 27695620
TI  - Temporal trends in the use of antidiabetic medicines: a nationwide 9-year study
      in older people living in New Zealand.
AB  - BACKGROUND: The global burden of diabetes is increasing worldwide. The aim of the
      study was to investigate the trends in use of antidiabetic medicines among older
      New Zealanders between 2005 and 2013, and to perform a separate analysis by age,
      sex, ethnicity, district health board domicile and socioeconomic deprivation
      index. METHODS: The study population included individuals' aged 65 years and
      older living in New Zealand (NZ) captured in the pharmaceutical collections.
      Repeated cross-sectional analysis of population-level dispensing data was
      conducted from 1 January 2005 to 31 December 2013. Linear regression model using
      a gamma link function was used to estimate prevalence ratios and trends between
      2005 and 2013. The main outcome measure was the prevalence of antidiabetic
      medicines in older New Zealanders. RESULTS: The prevalence of antidiabetic
      medicines in older New Zealanders increased by 17.6% between 2005 and 2013.
      Individuals in the 70-74 age group had the highest utilization of each of the
      classes of antidiabetic medicines and those aged ?85 had the lowest utilization.
      Among the antidiabetic class of medicines, utilization of sulfonylureas was
      highest and alpha-glucosidase inhibitors the least. The utilization of
      thiazolidinediones increased over the study period. In 2013, insulin isophane and
      insulin glargine were the most common insulin analogues used. Insulin use was
      high in those aged ?85 years across the entire study period. The utilization of
      metformin increased gradually throughout the study period (by 43.9% in 2013
      compared with 2005). CONCLUSION: This population-level study showed an increase
      in utilization of antidiabetic medicines in older people in NZ from 2005 to 2013;
      however, the increase does not seem to parallel the proportional increase in
      prevalence of diabetes for the study period. Improving access to newer
      antidiabetic medicines in line with emerging evidence should be a consideration
      for decision makers.

PMID- 27695621
TI  - Observed medical and surgical complications of prolonged barbiturate coma for
      refractory status epilepticus.
AB  - BACKGROUND: Refractory status epilepticus is often treated with third-line
      therapy, such as pentobarbital coma. However, its use is limited by side effects.
      Recognizing and preventing major and minor adverse effects of prolonged
      pentobarbital coma may increase good outcomes. This study retrospectively
      reviewed direct and indirect medical and surgical pentobarbital coma. METHODS:
      Retrospective chart review of all patients with refractory status epilepticus
      treated with pentobarbital over a 1 year period at a large tertiary care center.
      We collected baseline data, EEG data, and complications that were observed.
      RESULTS: Overall, nine patients [median age 46.4 (IQR 21.7, 75.5) years] were
      induced with pentobarbital coma median 11 (IQR 3, 33) days after seizure onset
      for a median of 9 (IQR 3.5, 45.4) days. A total of four to eight concurrent
      antiepileptics were tried prior to the pentobarbital coma. Phenobarbital, due to
      recurrence of seizures on weaning pentobarbital coma, was required in seven
      patients. Observed complications included peripheral neuropathy (77.8%), cerebral
      atrophy (33.3%), volume overload (44.4%), renal/metabolic (77.8%),
      gastrointestinal (66.6%), endocrine (55.6%), cardiac/hemodynamic/vascular
      (77.8%), respiratory (100%), and infectious (77.8%). The number of complications
      trended with duration of induced coma but was nonsignificant. Median ICU length
      of stay was 40 (IQR 28, 97.5) days. Overall, five patients were able to follow
      commands after a median 37 (IQR 25.5, 90) days from coma onset. There were eight
      patients that were discharged from hospital with three remaining in a prolonged
      unresponsive state. There was one patient that died prior to discharge.
      CONCLUSIONS: This study highlights the high morbidity in patients with refractory
      status epilepticus requiring pentobarbital coma. Anticipating and addressing the
      indirect and direct complications in prolonged pentobarbital coma may improve
      survival and functional outcomes in patients with refractory status epilepticus.

PMID- 27695619
TI  - The potential of gene therapy approaches for the treatment of hemoglobinopathies:
      achievements and challenges.
AB  - Hemoglobinopathies, including beta-thalassemia and sickle cell disease (SCD), are
      a heterogeneous group of commonly inherited disorders affecting the function or
      levels of hemoglobin. Disease phenotype can be severe with substantial morbidity
      and mortality. Bone marrow transplantation is curative, but limited to those
      patients with an appropriately matched donor. Genetic therapy, which utilizes a
      patient's own cells, is thus an attractive therapeutic option. Numerous therapies
      are currently in clinical trials or in development, including therapies utilizing
      gene replacement therapy using lentiviruses and the latest gene editing
      techniques. In addition, methods are being developed that may be able to expand
      gene therapies to those with poor access to medical care, potentially
      significantly decreasing the global burden of disease.

PMID- 27695622
TI  - Mirabegron in overactive bladder patients: efficacy review and update on drug
      safety.
AB  - Overactive bladder is a common condition, which significantly affects people's
      quality of life. The use of anticholinergic medication has been the mainstay of
      managing overactive bladder when conservative measures are not enough. Many
      patients stop anticholinergic medication because of the side effects and more
      recently the concerns about the effect of an anticholinergic burden and the
      development of dementia have been studied. Activation of beta3 adrenoceptors has
      been shown to relax the detrusor muscle and subsequently lead to the development
      of the first beta3 adrenoceptor agonist. Mirabegron is the first drug in this
      class to be approved for the use in overactive bladder. It has been extensively
      studied in phase II and III trials and has significant improvement in key
      overactive bladder parameters when compared with placebo. The incidence of side
      effects such as constipation, hypertension and tachycardia were comparable to
      anticholinergic medication but there was significantly less dry mouth incidence
      in the mirabegron groups. Mirabegron has been shown to be used safely in
      combination with solifenacin and tamsulosin. Head-to-head studies comparing
      efficacy and safety of mirabegron with anticholinergic medication would further
      help in the management strategy for overactive bladder.

PMID- 27695623
TI  - Anticholinergic medication use and dementia: latest evidence and clinical
      implications.
AB  - Use of medications with anticholinergic activity is widespread in older adults.
      Several studies have highlighted that anticholinergic use may be associated with
      an increased risk of dementia. The objective of this narrative review is to
      describe and evaluate studies of anticholinergic medication use and dementia and
      provide practical suggestions for avoiding use of these medications in older
      adults. A comprehensive review of the literature, citations from recent reviews
      and the author's personal files was conducted. Four studies were found that
      evaluated anticholinergic use and dementia as the primary outcome. Three studies
      focused on overall anticholinergic medication use and reported a statistically
      significantly increased risk of Alzheimer's disease or dementia. In one study,
      dementia risk was primarily found with higher cumulative doses; people using
      anticholinergic medications at the minimum effective dose recommended for older
      adults for at least 3 years were at highest risk. In contrast, a study conducted
      in nursing-home residents with depression did not find that paroxetine [a highly
      anticholinergic selective serotonin reuptake inhibitor antidepressant, (SSRI)]
      increased risk for dementia compared with other SSRIs (without anticholinergic
      activity). Further study is needed to understand the mechanism by which
      anticholinergic medications may increase risk. In conclusion, there is evidence
      from three observational studies suggesting that anticholinergic medications may
      increase dementia risk. Given this potential risk and the myriad of other well
      known adverse effects (i.e. constipation, blurred vision, urinary retention, and
      delirium) associated with anticholinergic medications, it is prudent for
      prescribers and older adults to minimize use of these medications and consider
      alternatives when possible.

PMID- 27695624
TI  - Citalopram and escitalopram: adverse cardiac outcomes in medically ill
      inpatients.

PMID- 27695625
TI  - Vascular Endothelial Growth Factor Increases Endothelial Nitric Oxide Synthase
      Transcription In Huvec Cells.
AB  - Although it is known that VEGF increases eNOS protein, the mechanisms responsible
      remain unclear. To determine if VEGF alters eNOS transcription, human umbilical
      vein endothelial cells were transfected with reporters under the control of the
      eNOS promoter and stimulated with VEGF165. VEGF significantly increased eNOS-mRNA
      after 2 hours exposure. VEGF significantly increased eNOS reporter activity as
      early as one hour (268+/-32%), but this increase returned to baseline after 6
      hours. Using deletion constructs, the VEGF response region was initially
      localized to within the -722/-494 region. GMSA indicated that VEGF increased DNA
      binding to both a cAMP-like and AP1-like response elements. Site-specific
      mutations and heterologous constructs indicated that the site centered at AP1
      like site was both necessary and sufficient to meditate VEGF transcriptional
      activation. These results indicate that VEGF rapidly activates eNOS transcription
      prior to a rise eNOS-mRNA, an effect mediated by a cis-trans interaction
      localized to an AP1-like site within the eNOS promoter.

PMID- 27695626
TI  - Thermal time constant: optimising the skin temperature predictive modelling in
      lower limb prostheses using Gaussian processes.
AB  - Elevated skin temperature at the body/device interface of lower-limb prostheses
      is one of the major factors that affect tissue health. The heat dissipation in
      prosthetic sockets is greatly influenced by the thermal conductive properties of
      the hard socket and liner material employed. However, monitoring of the interface
      temperature at skin level in lower-limb prosthesis is notoriously complicated.
      This is due to the flexible nature of the interface liners used which requires
      consistent positioning of sensors during donning and doffing. Predicting the
      residual limb temperature by monitoring the temperature between socket and liner
      rather than skin and liner could be an important step in alleviating complaints
      on increased temperature and perspiration in prosthetic sockets. To predict the
      residual limb temperature, a machine learning algorithm - Gaussian processes is
      employed, which utilizes the thermal time constant values of commonly used socket
      and liner materials. This Letter highlights the relevance of thermal time
      constant of prosthetic materials in Gaussian processes technique which would be
      useful in addressing the challenge of non-invasively monitoring the residual limb
      skin temperature. With the introduction of thermal time constant, the model can
      be optimised and generalised for a given prosthetic setup, thereby making the
      predictions more reliable.

PMID- 27695627
TI  - Epigenetic Mechanisms: New Targets for Heart Failure Pharmacopuncture.

PMID- 27695628
TI  - Effects of Acupuncture Stimulation on the Radial artery's Pressure Pulse Wave in
      Healthy Young Participants: Protocol for a prospective, single-Arm, Exploratory,
      Clinical Study.
AB  - INTRODUCTION: This study aims to investigate the effects of acupuncture
      stimulation on the radial artery's pressure pulse wave, along with various
      hemodynamic parameters, and to explore the possible underlying mechanism of pulse
      diagnosis in healthy participants in their twenties. METHODS AND ANALYSIS: This
      study is a prospective, single-arm, exploratory clinical study. A total of 25
      healthy participants, without regard to gender, in their twenties will be
      recruited by physicians. Written informed consent will be obtained from all
      participants. The participants will receive acupuncture once at ST36 on both
      sides. The radial arterial pulse waves will be measured on the left arm of the
      subjects by using an applicable pulse tonometric device (KIOM-PAS). On the right
      arm (appearing twice), electrocardiogram (ECG), photoplethysmogram (PPG),
      respiration and cardiac output (CO) signals, will be measured using a
      physiological data acquisition system (Biopac module), while the velocity of
      blood flow, and the diameter and the depth of the blood vessel will be measured
      using an ultrasonogram machine on the right arm (appearing twice). All
      measurements will be conducted before, during, and after acupuncture. The primary
      outcome will be the spectral energy at high frequencies above 10 Hz (SE10-30Hz)
      calculated from the KIOM-PAS device signal. Secondary outcomes will be various
      variables obtained from the KIOM-PAS device, ECG, PPG, impedance cardiography
      modules, and an ultrasonogram machine. DISCUSSION: The results of this trial will
      provide information regarding the physiological and the hemodynamic mechanisms
      underlying acupuncture stimulation and clinical evidence for the influence of
      acupuncture on the pressure pulse wave in the radial artery. ETHICS AND
      DISSEMINATION: This study was approved by the Institutional Review Board (IRB) of
      Kyung Hee University's Oriental Medical Center, Seoul, Korea (KOMCIRB-150818-HR
      030). The study findings will be published in peer-reviewed journals and
      presented at national and international conferences. TRIAL REGISTRATION NUMBER:
      This trial was registered with the Clinical Research Information Service (CRIS)
      at the Korea National Institute of Health (NIH), Republic of Korea (KCT0001663),
      which is a registry in the World Health Organization's (WHO's) Registry Network.

PMID- 27695629
TI  - Nonlinear Conte-Zbilut-Federici (CZF) Method of Computing LF/HF Ratio: A More
      Reliable Index of Changes in Heart Rate Variability.
AB  - OBJECTIVES: Acupuncture treatments are safe and effective for a wide variety of
      diseases involving autonomic dysregulation. Heart rate variability (HRV) is a
      noninvasive method for assessing sympathovagal balance. The low frequency/high
      frequency (LF/HF) spectral power ratio is an index of sympathovagal influence on
      heart rate and of cardiovascular health. This study tests the hypothesis that
      from rest to 30% to 50% of peak oxygen consumption, the nonlinear Conte-Zbilut
      Federici (CZF) method of computing the LF/HF ratio is a more reliable index of
      changes in the HRV than linear methods are. METHODS: The subjects of this study
      were 10 healthy young adults. Electrocardiogram RR intervals were measured during
      6-minute periods of rest and aerobic exercise on a cycle ergometer at 30% and 50%
      of peak oxygen consumption (VO2peak). RESULTS: The frequency domain CZF
      computations of the LF/HF ratio and the time domain computations of the standard
      deviation of normal-to-normal intervals (SDNN) decreased sequentially from rest
      to 30% VO2peak (P < 0.001) to 50% VO2peak (P < 0.05). The SDNN and the CZF
      computations of the LF/HF ratio were positively correlated (Pearson's r = 0.75, P
      < 0.001). fast Fourier transform (FFT), autoregressive (AR) and Lomb periodogram
      computations of the LF/HF ratio increased only from rest to 50% VO2peak.
      CONCLUSION: Computations of the LF/HF ratio by using the nonlinear CZF method
      appear to be more sensitive to changes in physical activity than computations of
      the LF/HF ratio by using linear methods. Future studies should determine whether
      the CZF computation of the LF/HF ratio improves evaluations of pharmacopuncture
      and other treatment modalities.

PMID- 27695630
TI  - General and Genetic Toxicology of Enzyme-Treated Ginseng Extract: Toxicology of
      Ginseng Rh2.
AB  - OBJECTIVES: Ginseng Rh2+ is enzyme-treated ginseng extract containing high
      amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have
      potent anticancer activity. We conducted general and genetic toxicity tests to
      evaluate the safety of ginseng Rh2+. METHODS: An acute oral toxicity test was
      performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A
      14-day range-finding study was also conducted to set dose levels for the 90-day
      study. A subchronic 90-day toxicity study was performed at dose levels of 1,000
      and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL)
      of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng
      Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid
      requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a
      chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo
      micronucleus test using ICR mice bone marrow as recommended by the Korean
      Ministry of Food and Drug Safety. RESULTS: According to the results of the acute
      oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was
      estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological
      effect of ginseng Rh2+ was observed in body-weight changes, food consumption,
      clinical signs, organ weights, histopathology, ophthalmology, and clinical
      pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and
      no target organ was found in this test. In addition, no evidence of mutagenicity
      was found either on the in vitro genotoxicity tests, including the Ames test and
      the chromosome aberration test, or on the in vivo in mice bone marrow
      micronucleus test. CONCLUSION: On the basis of our findings, ginseng Rh2+ is a
      non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used
      as a novel adjuvant anticancer agent that is safe for long-term administration.

PMID- 27695631
TI  - Bee Venom (Apis Mellifera) an Effective Potential Alternative to Gentamicin for
      Specific Bacteria Strains: Bee Venom an Effective Potential for Bacteria.
AB  - OBJECTIVES: Mellitine, a major component of bee venom (BV, Apis mellifera), is
      more active against gram positive than gram negative bacteria. Moreover, BV has
      been reported to have multiple effects, including antibacterial, antivirus, and
      anti-inflammation effects, in various types of cells. In addition, wasp venom has
      been reported to have antibacterial properties. The aim of this study was to
      evaluate the antibacterial activity of BV against selected gram positive and gram
      negative bacterial strains of medical importance. METHODS: This investigation was
      set up to evaluate the antibacterial activity of BV against six grams positive
      and gram negative bacteria, including Staphylococcus aureus (S. aureus),
      Salmonella typhimurium, Escherichia coli (E. coli) O157:H7, Pseudomonas
      aeruginosa, Burkholderia mallei and Burkholderia pseudomallei. Three
      concentrations of crude BV and standard antibiotic (gentamicin) disks as positive
      controls were tested by using the disc diffusion method. RESULTS: BV was found to
      have a significant antibacterial effect against E. coli, S. aureus, and
      Salmonella typhyimurium in all three concentrations tested. However, BV had no
      noticeable effect on other tested bacteria for any of the three doses tested.
      CONCLUSION: The results of the current study indicate that BV inhibits the growth
      and survival of bacterial strains and that BV can be used as a complementary
      antimicrobial agent against pathogenic bacteria. BV lacked the effective proteins
      necessary for it to exhibit antibacterial activity for some specific strains
      while being very effective against other specific strains. Thus, one may
      conclude, that Apis mellifera venom may have a specific mechanism that allows it
      to have an antibacterial effect on certain susceptible bacteria, but that
      mechanism is not well understood.

PMID- 27695632
TI  - Assessment of the Toxicity and the Stability of Saeng Mak San by Using Repeated
      Intravenous Injections in Sprague-Dawley Rats.
AB  - OBJECTIVES: This study used repeated intravenous injections of Saeng Maek San
      (SMS) injection in Sprague-Dawley (SD) rats to assess the toxicity and the
      stability of SMS. METHODS: Six-week-old male and female SD rats reared by Orient
      bio Inc were chosen for this pilot study. They were randomly split into four
      groups: Group 1 (G1), the control group (0.3 mL of normal saline
      solution/day/animal), and Groups 2, 3 and 4 (G2, G3 and G4), the experimental
      groups (0.1, 0.2 and 0.3 mL/day/animal of SMS), respectively. Each animal
      received an intravenous injection of SMS once a day for four weeks. Clinical
      signs, body weight changes, and food consumption were monitored during the
      observation period, and urinalysis and hematology were conducted after four weeks
      of SMS or saline administration. RESULTS: No deaths occurred in any of the four
      groups during the observation period. Compared to the control group, male and
      female rats in groups 3 and 4 (0.2 and 0.3 mL/animal/day) showed hemoglobinuria,
      but the low-dosage group (G2, 0.1 mL/animal/day) showed no significant changes in
      the clinical signs test. No significant changes due to SMS were observed in the
      experimental groups regarding body weight changes, food consumption urinalysis,
      or hematology. CONCLUSION: During this study, no mortalities were observed in any
      of the experimental groups and no hemoglobinuria was observed in the low dosage
      group (0.1 mL/animal/day) while it was intermittently observed in groups 3 and 4
      (0.2 and 0.3 mL/animal/day). Thus, we suggest that the no-observed adverse-effect
      level (NOAEL) is 0.1 mL/animal/day in male and female SD rats.

PMID- 27695633
TI  - Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching
      Behavior in Mice: Effect of Agarwood on Histamine Release and Scratching
      Behavior.
AB  - OBJECTIVES: This study was conducted to clarify the effects of agarwood on
      histamine release from mast cells in rats and on the scratching behaviors in
      mice. METHODS: Histamine release from rat mast cells induced by compound 48/80 or
      concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice
      were examined to investigate the effects of agarwood. The hyaluronidase activity
      and the 3',5'-cyclic adenosine monophosphate (cAMP) levels in mast cells were
      examined to investigate the mechanisms for the inhibition of histamine release.
      The correlation between the inhibitory effects of agarwood on histamine release
      and the content of its typical ingredients, a 2-(2-phenylethyl)chromone
      derivatives, was analyzed using thin-layer chromatography. RESULTS: Agarwood
      showed an inhibitory effect on mast-cell histamine release induced by compound
      48/80 or Con A without any effect on hyaluronidase activity; this effect involves
      an increase in the cAMP levels in mast cells. Oral administration of agarwood
      showed an inhibitory effect on compound 48/80-induced scratching behavior in
      mice. The inhibitory effects of agarwood on histamine release were quite
      different, depending on the area where the agarwood was produced, its quality,
      and its market price. No correlation was found between the inhibitory effects of
      agarwood on histamine release and the typical ingredients of agarwood, which are
      2-(2-phenylethyl)chromone derivatives. CONCLUSION: These results show that
      agarwood inhibits histamine release from mast cells partially through an increase
      in the cAMP levels in cells. We suggest that some active ingredients of agarwood
      must be effective on oral intake and that agarwood can be used to treat patients
      with a number of conditions, including urticaria, atopic dermatitis, and
      bronchial asthma, in which an increase in histamine release occurs. Differences
      in the pharmacological effects of this crude drug among markets may provide
      important information for the quality control of this herbal medicine.

PMID- 27695634
TI  - Phenol-Rich Compounds Sweet Gel: A Statistically More Effective Antibiotic than
      Cloxacillin Against Pseudomonas Aeruginosa.
AB  - OBJECTIVES: The purpose of this study was to obtain a natural antibiotic from
      Phenol-rich compounds; for the dressing and the treatment of chronic wounds.
      METHODS: The Phenol-rich compound sweet gel was prepared by blending four natural
      herbal extracts, Acacia catechu (L.F.), Momia (Shilajit), Castanea sativa, and
      Ephedra sinica stapf, with combination of a sweet gel medium, including honey,
      maple saps, Phoenix dactylifera L. (date), pomegranate extract and Azadirachta
      indica gum as a stabilizer. The combinations were screened by using a well
      diffusion assay with cloxacillin as a control. Pseudomonas spp. was tested with
      our novel antimicrobial compound. The zones of inhibition in agar culture were
      measured for each individual component and for the compound, and the results were
      compared with those of the control group which had been treated with cloxacillin.
      Data were expressed as means +/- standard deviations. Quantitative analyses were
      performed using the paired t-test. RESULTS: The antibiotic effect of the Phenol
      rich compound sweet gel was statistically shown to be more significant than that
      of cloxacillin against Pseudomonas aeruginosa (P < 0.05). CONCLUSION: Our novel
      approach to fighting the antibiotic resistance of Pseudomonas proved to be
      successful. The Phenol-rich compound sweet gel was found to be suitable for use
      as an alternative medicine and bioactive dressing material, for the treatment of
      patients with various types of wounds, including burns, venous leg ulcers, ulcers
      of various etiologies, leg ulcers on the feet of diabetic, unhealed graft
      sampling sites, abscesses, boils, surgical wounds, necrotic process, post
      operative and neonatal wound infection, and should be considered as an
      alternative to the usual methods of cure.

PMID- 27695635
TI  - Toxicity and Safety Profiles of Methanolic Extract of Pistacia integerrima J. L.
      Stewart ex Brandis (PI) for Wistar Rats.
AB  - OBJECTIVES: The goals of this research were to evaluate acute (single-dose) and
      sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia
      integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the
      safety profile of PI by observing physiological changes, mortality, changes in
      body weight, the histopathology of body organs, the hematology and the
      biochemistry of the animals. METHODS: The toxicity profile of PI was evaluated
      using Wistar rats of both sexes. Animals were divided into four groups: Group 1;
      control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500
      mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals
      received a single dose of PI extract (2,000 mg/ kg) and were then observed for 14
      days for changes in skin, fur, eye color, mucous membrane secretions and
      excretions, gait, posture, and tonic or clonic movements was performed according
      to guideline 425 of the Organization of Economic and Corporation Development
      (OECD). In the repeated-dose toxicity study (OECD - 407) animals received a daily
      dose of PI extract for 28 days (4 weeks). The parameters observed in this study
      include body weight, hematology and biochemistry of the animals. RESULTS: In the
      acute toxicity study, no mortalities or changes in behavior were noted in the
      animals. The repeated-dose toxicity study was also devoid of any toxicity in the
      animals during the 28 days of testing with PI extract. The extract did not alter-
      the body weight, hematology or biochemistry of the animals. The methanolic
      extract of PI was to be found safe to the no-observed-adverse-effect-level
      (NOAEL) for the single- dose and repeated-dose toxicity tests in rats.
      CONCLUSION: The methanolic extract of PI was devoid of toxicity; hence, it can be
      used for various ayurvedic preparations and treatments of diseases.

PMID- 27695636
TI  - Combination Therapy of Gefitinib and Korean Herbal Medicines Could be a
      Beneficial Option for Patients with Non-Small-Cell Lung Cancer.
AB  - ABSTRACT:  ABSTRACT: Lung cancer has a high mortality rate and is often diagnosed
      at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used
      to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal
      medicines may also have therapeutic efficacy against lung cancer, reduce the side
      effects associated with chemotherapy, and improve patient quality of life (QOL).
      This case report describes the effects of a Korean herbal medicine regimen
      combined with gefitinib in a patient with NSCLC and bone metastasis. The Korean
      herbal medicine regimen included woohwanggeosa-dan, hwanggibujeong-dan and
      geonchilgyebok-jeong. The computed tomography (CT) findings showed that following
      combination treatment, the size of the tumor was markedly decreased without
      serious adverse events. Moreover, the Eastern Cooperative Oncology Group (ECOG)
      performance status was improved and cancer-related pain was decreased. These
      results suggest that a combination of Korean herbal medicines and gefitinib may
      be an effective therapeutic option for patients with advanced NSCLC and bone
      metastasis. Further studies are needed to examine the mechanism and the clinical
      efficacy of Korean herbal medicines against NSCLC. Lung cancer has a high
      mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a
      targeted molecular therapeutic drug used to treat patients with non-small-cell
      lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy
      against lung cancer, reduce the side effects associated with chemotherapy, and
      improve patient quality of life (QOL). This case report describes the effects of
      a Korean herbal medicine regimen combined with gefitinib in a patient with NSCLC
      and bone metastasis. The Korean herbal medicine regimen included woohwanggeosa
      dan, hwanggibujeong-dan and geonchilgyebok-jeong. The computed tomography (CT)
      findings showed that following combination treatment, the size of the tumor was
      markedly decreased without serious adverse events. Moreover, the Eastern
      Cooperative Oncology Group (ECOG) performance status was improved and cancer
      related pain was decreased. These results suggest that a combination of Korean
      herbal medicines and gefitinib may be an effective therapeutic option for
      patients with advanced NSCLC and bone metastasis. Further studies are needed to
      examine the mechanism and the clinical efficacy of Korean herbal medicines
      against NSCLC.

PMID- 27695637
TI  - Mapping paddy rice distribution using multi-temporal Landsat imagery in the
      Sanjiang Plain, northeast China.
AB  - Information of paddy rice distribution is essential for food production and
      methane emission calculation. Phenology-based algorithms have been utilized in
      the mapping of paddy rice fields by identifying the unique flooding and seedling
      transplanting phases using multi-temporal moderate resolution (500 m to 1 km)
      images. In this study, we developed simple algorithms to identify paddy rice at a
      fine resolution at the regional scale using multi-temporal Landsat imagery.
      Sixteen Landsat images from 2010-2012 were used to generate the 30 m paddy rice
      map in the Sanjiang Plain, northeast China-one of the major paddy rice
      cultivation regions in China. Three vegetation indices, Normalized Difference
      Vegetation Index (NDVI), Enhanced Vegetation Index (EVI), and Land Surface Water
      Index (LSWI), were used to identify rice fields during the flooding/transplanting
      and ripening phases. The user and producer accuracies of paddy rice on the
      resultant Landsat-based paddy rice map were 90% and 94%, respectively. The
      Landsat-based paddy rice map was an improvement over the paddy rice layer on the
      National Land Cover Dataset, which was generated through visual interpretation
      and digitalization on the fine-resolution images. The agricultural census data
      substantially underreported paddy rice area, raising serious concern about its
      use for studies on food security.

PMID- 27695639
TI  - Caries Experience and Periodontal Status during Pregnancy in a Group of Pregnant
      Women with HIV+ Infections from Puerto Rico.
AB  - OBJECTIVES: The aim of this study was to determine the caries rate and
      periodontal status in a sample of pregnant women with HIV+ infections from Puerto
      Rico. METHODS: A pilot study was conducted on a cross sectional convenience
      sample of 25 pregnant women with HIV+ infections from Puerto Rico who visit the
      CEMI clinic (Centro de Estudios Materno Infantil) at the University of Puerto
      Rico. The women subjects were evaluated for caries, DMFT (D: Decay tooth; M:
      Missing tooth due to caries; F: Filled tooth) index, oral lesions associated with
      HIV+/AIDS and periodontal disease parameters, with a Florida probe by a
      calibrated dentist on periodontal indexes such as as bleeding on probing, CEJ
      (cemento-enamel junction) and pocket depth. Periodontal disease was classified as
      having 4 sites with pocket depth greater than 4 mm and caries were identified
      following the Radike criteria. Data was statistically analyzed using the SSPS
      Program (Statistical Software Program for Social Sciences) and descriptive
      statistics were calculated. RESULTS: Mean DT (decayed teeth), MT (missing teeth
      due to caries), FT (filled teeth) and DMFT (decay, missing and filled teeth) were
      4.8, 1.86, 5.3 and 12, respectively; mean sites of bleeding on probing=12.06;
      mean sites with pocket depth>4 mm=6.95 and mean sites with loss of attachment
      greater than 4 mm=7.66. [Almost 50% of the patients had generalized chronic
      periodontitis. A 72% prevalence of periodontal disease was found. No oral lesions
      related to HIV+/AIDS were reported. CD4 and viral load was statistically
      associated with bleeding on probing and severe signs of periodontal disease.
      CONCLUSIONS: High levels of dental disease were found in pregnant women with
      HIV+/AIDS infections from Puerto Rico, and these women were in need of
      substantial dental services.

PMID- 27695638
TI  - Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to
      Substance Use, Cognition, and Self-Regulation.
AB  - OBJECTIVE: Proton magnetic resonance spectroscopy (1H MRS) in opiate dependence
      showed abnormalities in neuronal viability and glutamate concentration in the
      anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal
      cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological
      correlates have not been investigated in opiate dependence. METHODS: Single
      volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21
      opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results
      were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC),
      commonly investigated treatment-seekers providing context for OD evaluation.
      Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto
      occipital cortical (POC) regions. RESULTS: Compared to CON, OD had lower
      concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine
      +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and
      mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC
      and gamma-aminobutyric acid (GABA) concentration did not differ between groups in
      any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA
      and choline containing metabolites (Cho) correlated with poorer working memory,
      executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC
      GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and
      choline-containing metabolites were elevated and lower Cr concentration related
      to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had
      significant DLPFC metabolite deficits. CONCLUSION: The anterior frontal
      metabolite profile of OD differed significantly from that of CON and ALC. The
      frontal lobe metabolite abnormalities in OD and their neuropsychological
      correlates may play a role in treatment outcome and could be explored as specific
      targets for improved OD treatment.

PMID- 27695640
TI  - Three common misuses of P values.
AB  - "Significance" has a specific meaning in science, especially in statistics. The p
      value as a measure of statistical significance (evidence against a null
      hypothesis) has long been used in statistical inference and has served as a key
      player in science and research. Despite its clear mathematical definition and
      original purpose, and being just one of the many statistical measures/criteria,
      its role has been over-emphasized along with hypothesis testing. Observing and
      reflecting on this practice, some journals have attempted to ban reporting of p
      values, and the American Statistical Association (for the first time in its 177
      year old history) released a statement on p-values in 2016. In this article, we
      intend to review the correct definition of the p-value as well as its common
      misuses, in the hope that our article is useful to clinicians and researchers.

PMID- 27695642
TI  - Faculty Development Programming at Academic Medical Centers: Identifying
      Financial Benefits and Value.

PMID- 27695641
TI  - Cell Intrinsic Factors Modulate the Effects of IFNgamma on the Development of
      Chlamydia trachomatis.
AB  - Chlamydia trachomatis is an obligate intracellular bacterial pathogen that cannot
      synthesize several amino acids, including tryptophan. Rather, C. trachomatis
      acquires these essential metabolites from its human host cell. Chlamydial
      dependence on host-provided tryptophan underlies a major host defense mechanism
      against the bacterium; namely, the induction of the host tryptophan-catabolizing
      enzyme, indoleamine 2,3- dioxygenase (IDO1) by interferon gamma (IFNgamma), which
      leads to eradication of C. trachomatis by tryptophan starvation. For this reason,
      IFNgamma is proposed to be the major host protective cytokine against genital C.
      trachomatis infections. The protective effect of IFNgamma against C. trachomatis
      can be recapitulated in vitro using epithelial cell-lines such as the cervical
      carcinoma derived cell-line Hela, the Hela subclone HEp-2, and the cervical
      carcinoma derived cell-line ME180. Addition of IFNgamma to these cells infected
      with C. trachomatis results in a strong bactericidal or bacteriostatic effect
      dependent on the concentration of IFNgamma administered. Unlike Hela, HEp-2, and
      ME180, there are other human epithelial, or epithelial-like cell-lines where
      administration of IFNgamma does not affect chlamydial replication, although they
      express the IFNgamma receptor (IFNGR). In this report, we have characterized the
      mechanisms that underlie this dichotomy using the cell-lines C33A and 293. Akin
      to Hela, C33A is derived from a human cervical carcinoma, while 293 cells were
      produced by transfection of adenovirus type 5 DNA into embryonic kidney cells. We
      demonstrate that although IFNGR is expressed at high levels in C33A cells, its
      ligation by IFNgamma does not result in STAT1 phosphorylation, an essential step
      for activation of the IDO1 promoter. Our results indicate that although the
      IFNgamma-dependent signaling cascade is intact in 293 cells; the IDO1 promoter is
      not activated in these cells because it is epigenetically silenced, most likely
      by DNA methylation. Because polymorphisms in IFNgamma, IFNGR, and the IDO1
      promoter are known to affect other human infections or diseased states, our
      results indicate that the effect of allelic differences in these genes and the
      pathways they activate should be evaluated for their effect on C. trachomatis
      pathology.

PMID- 27695643
TI  - Francisella tularensis - Immune Cell Activator, Suppressor, or Stealthy Evader:
      The Evolving View from the Petri Dish.
AB  - One of the hallmarks of pulmonary tularemia, which results from inhalation of
      Francisella tularensis - a significant bioterrorism concern, is the lack of an
      acute TH1-biased inflammatory response in the early phase of disease (days 1-3)
      despite significant bacterial loads. In an effort to understand this apparent
      hypo-responsiveness, many laboratories have utilized in vitro cell-based models
      as tools to probe the nature and consequences of host cell interactions with F.
      tularensis. The first uses of this model suggested that mammalian host cells
      recognize this bacterium principally through TLR2 to evoke a robust, classical
      TH1-biased cytokine response including TNF, IL-6, IL-1beta, and IFN-gamma. Others
      used this model in concert with a variety of non-genetic perturbations of the
      bacterial-host cell interaction and suggested that F. tularensis actively
      suppressed the cellular response. Consistent with this notion, others engaged
      this model to assess isogenic mutants and, in many cases, found the mutant
      bacteria to be more pro-inflammatory than their WT counter-parts. Frequently,
      these observations were interpreted as evidence for the immunosuppressive
      function of the gene of interest. However, recently appreciated roles of the
      health of the bacterium and the impact of host factors have refined this model to
      suggest a "stealthy" mode of bacterial-host cell interaction (rather than one
      involving active suppression) consistent with the observations during early phase
      disease.

PMID- 27695644
TI  - Neonatal Enterovirus Infection: Case Series of Clinical Sepsis and Positive
      Cerebrospinal Fluid Polymerase Chain Reaction Test with Myocarditis and Cerebral
      White Matter Injury Complications.
AB  - Objective We describe five neonates with enteroviral (EV) infection to
      demonstrate central nervous system (CNS) and cardiac complications and report
      successful treatment of myocarditis with immunoglobulin intravenous (IVIG) in
      two. Study Design Case series identified during three enteroviral seasons in one
      neonatal intensive care unit (NICU) by cerebral spinal fluid (CSF) reverse
      transcriptase polymerase chain reaction (PCR) testing for EV in neonates
      suspected to have sepsis, but with sterile bacterial cultures. Results Cases were
      identified in each of three sequential years in a NICU with 800 to 900
      admissions/year. Two cases were likely acquired perinatally; all were symptomatic
      with lethargy and poor feeding by age 5 to 10 days. All had signs of sepsis
      and/or meningitis; one progressed to periventricular leukomalacia and
      encephalomalacia. Two recovered from myocarditis after treatment that included
      IVIG 3 to 5 g/kg. Conclusion Neonates who appear septic without bacterial
      etiology may have EV CNS infections that can be diagnosed rapidly by CSF PCR
      testing. Cases may be underdiagnosed in the early neonatal period if specific
      testing is not performed. Neonates with EV infection should be investigated for
      evidence of periventricular leukomalacia, screened for myocarditis, and
      considered for IVIG treatment.

PMID- 27695645
TI  - Targeting Glioma with a Dual Mode Optical and Paramagnetic Nanoprobe across the
      Blood-brain Tumor Barrier.
AB  - In brain tumors, delivering nanoparticles across the blood-tumor barrier presents
      major hurdles. A clinically relevant MRI contrast agent, GdDOTA and a near
      infrared (NIR) fluorescent dye, DL680 were conjugated to a G5 PAMAM dendrimer,
      thus producing a dual-mode MRI and NIR imaging agent. Systemic delivery of the
      subsequent nano-sized agent demonstrated glioma-specific accumulation, probably
      due to the enhanced permeability and retention effect. In vivo MRI detected the
      agent in glioma tissue, but not in normal contralateral tissue; this observation
      was validated with in vivo and ex vivo fluorescence imaging. A biodistribution
      study showed the agent to have accumulated in the glioma tumor and the liver, the
      latter being the excretion path for a G5 dendrimer-based agent.

PMID- 27695646
TI  - The Impact of Strong for Life on the Physical Functioning and Health of Older
      Adults Receiving Home and Community-Based Services.
AB  - BACKGROUND/OBJECTIVES: To test the effects of Strong for Life (SFL) on the
      physical performance and self-rated health of older adults receiving Home and
      Community-Based Services (HCBS). DESIGN: Randomized, two-group trial with pre
      post measures. SETTING: In-home exercise program. PARTICIPANTS: Clients aged 65
      95 (n=42) and their Home Care Aide (HCA) (n=32) were randomly assigned to a usual
      care and SFL intervention or usual care control group. INTERVENTION: Clients were
      instructed in SFL by their HCA and completed SFL 3 times per week for 12-weeks.
      MEASUREMENTS: Outcomes included grip and quadriceps strength, Timed Up and Go,
      gait speed, Self-Efficacy for Exercise, pain, and PROMIS-global health measured
      at baseline and immediately following the intervention. Clients completed opened
      ended survey items on SFL program evaluation. RESULTS: Effect sizes were moderate
      for grip strength (d= .38), pain (d= .34), and PROMIS-global health (d= .27).
      Small effect sizes were found for all other measures. Median quadriceps and TUG
      scores differentially improved among intervention participants versus controls.
      No adverse health events and high program satisfaction were reported. Frailty
      prevalence in the control group increased between baseline and post-test while
      frailty prevalence in the intervention group decreased during the same time
      period. CONCLUSION: Strong for Life has the potential to improve the strength,
      mobility, health, and frailty of older adults receiving HCBS. This study provides
      initial evidence of the impact of SFL for older adults receiving HCBS, as well as
      the safety of the intervention evidenced by the lack of reported adverse events.

PMID- 27695647
TI  - Chemotherapy for Elderly Ovarian Cancer Patients.
AB  - OBJECTIVE: Ovarian cancer is the most lethal cancer involving the female pelvic
      reproductive system. Its incidence increases with age and with an aging
      population, its prevalence should also increase. The goal of our retrospective
      study is to report our experience in treating women over 65 years of age, with a
      diagnosis of primary ovarian cancer, using standard intravenous chemotherapy.
      METHODS: The medical records of 78 patients>65 years of age diagnosed with
      primary ovarian cancer at the Yale Cancer Center between 1996-2006 were
      retrospectively reviewed and included in our analysis. Patients had stage I-IV
      disease (stage I n=5, stage II n=8, stage III n=36, stage IV n=25, unknown n=4).
      RESULTS: Sixty-three of 78 women (80.8%) completed the prescribed regimen; and 62
      women did not require a dose reduction or chemotherapy discontinuation. The most
      common reason for a dose reduction or treatment discontinuation was fatigue
      (6.4%), neutropenia (2.6%), patient preference (2.6%), and multiple co
      morbidities (2.6%). The most commonly used regimen was paclitaxel 175mg/m2 and
      carboplatin AUC 5. The hazard ratio for PFS and OS for patients who had dose
      reduction/discontinuation versus those who completed the prescribed dose was 1.3
      (95% CI 0.51-3.26) and 0.63 (95% CI 0.17-2.33), respectively. CONCLUSIONS: Our
      findings illustrate that elderly women are able to tolerate standard chemotherapy
      with relatively few significant adverse effects. While different treatment
      modalities in ovarian cancer are continually being evaluated, additional
      prospective studies are required to better understand the tolerability and
      efficacy of such treatment in the elderly population.

PMID- 27695648
TI  - Shape Effect of Glyco-Nanoparticles on Macrophage Cellular Uptake and Immune
      Response.
AB  - The shells of various poly(dl-lactide)-b-poly(acrylic acid) (PDLLA-b-PAA)
      spherical micelles and poly(l-lactide)-b-poly(acrylic acid) (PLLA-b-PAA)
      cylindrical micelles were functionalized with mannose to yield glyco
      nanoparticles (GNPs) with different shapes and dimensions. All of these GNPs were
      shown to have good biocompatibility (up to 1 mg/mL). Cellular uptake experiments
      using RAW 264.7 have shown that the spherical GNPs were internalized to a much
      greater extent than the cylindrical GNPs and such a phenomenon was attributed to
      their different endocytosis pathways. It was demonstrated that spherical GNPs
      were internalized based on clathrin- and caveolin-mediated endocytosis while
      cylindrical GNPs mainly depended on clathrin-mediated endocytosis. We also found
      that longer cylindrical GNPs (Ln * Wn = 215 * 47 nm) can induce an inflammatory
      response (specifically interleukin 6) more efficiently than shorter cylindrical
      GNPs (Ln * Wn = 99 * 50 nm) and spherical GNPs (Dn = 46 nm).

PMID- 27695649
TI  - Marriage shrines and worms impacting our understanding of mammalian
      fertilization.
AB  - Genetic approaches in C. elegans are complementing the biochemical and antibody
      based strategies traditionally used to study the molecular underpinnings of
      fertilization in other organisms. A pair of worm studies, one based on forward
      genetics and one based on reverse genetics, converge on the sperm immunoglobulin
      superfamily molecule SPE-45. Loss of spe-45 function leads to the production of
      sperm that cannot fertilize wild-type eggs. This is a strikingly similar
      phenotype as those seen in mice lacking the immunoglobulin superfamily protein
      Izumo1. This work sets the stage for leveraging the power of the C. elegans model
      system to learn more about Izumo-like molecular function but also for the
      discovery of additional deeply conserved components of fertility pathways.

PMID- 27695651
TI  - New insights into old worm proteomes.
AB  - Aging is accompanied by large-scale changes in the proteome, which could have
      important consequences for cellular and organismal physiology. In this
      commentary, we review recent studies characterizing the aging proteome in C.
      elegans. We assess the evidence that the rates of protein synthesis, folding, and
      degradation change with age in C. elegans, and evaluate whether changes in these
      pathways limit normal lifespan. We also discuss large-scale studies measuring
      changes in the proteome with age that suggest that a failure to excrete
      reproductive proteins in post-reproductive animals plays a role in changing
      protein levels with age.

PMID- 27695650
TI  - Globin-based redox signaling.
AB  - In recent years, moderate levels of reactive oxygen species (ROS) have become
      recognized as signaling cues that participate at all levels of cellular
      organization. Globins, with their redox-active heme iron and ubiquitous presence,
      seem ideally suited to participate in ROS metabolism. Here we comment on our
      recent findings that show the participation of a globin, GLB-12, in a redox
      signaling pathway in Caenorhabditis elegans. We found that GLB-12 produces
      superoxide, a type of ROS, after which this is converted to what appears to be a
      hydrogen peroxide gradient over the plasma membrane by the activity of
      intracellular and extracellular superoxide dismutases. In the first part, we
      discuss in more detail the different regulatory mechanisms that increase the
      effectiveness of this redox signal. In the second part, we comment on how
      specific structural and biochemical properties allow this globin to perform redox
      reactions. Interestingly, these properties are also observed in 2 other C.
      elegans globins that appear to be involved in redox biology. We therefore
      hypothesize that globins involved in redox signaling display similar structural
      and biochemical characteristics and propose that a subgroup of globins can be
      added to the group of proteins that play a vital role in redox signaling.

PMID- 27695652
TI  - Current advances in the functional studies of fatty acids and fatty acid-derived
      lipids in C. elegans.
AB  - Fatty acids and fatty acid-derived lipids (FAs/FADLs) play essential roles in
      many living organisms, including contributions to membrane structure and
      signaling transduction. Aberrant metabolism of FAs/FADLs often causes diseases
      and health problems. However, the detailed mechanistic studies of specific
      FAs/FADLs in vivo are limited. C. elegans has been an effective model system for
      FA/ FADL studies due to its powerful genetics and conserved lipid biosynthetic
      pathways. The recently developed high-throughput analytic tools also enable
      sophisticated profiling of lipids molecules in C. elegans, which is critical for
      understanding their specific functions. Here we review a subset of current
      advances in FA/FADL functional studies in C. elegans.

PMID- 27695654
TI  - Gamete interactions require transmembranous immunoglobulin-like proteins with
      conserved roles during evolution.
AB  - C. elegans spe-9 class genes are male germline-enriched in their expression and
      indispensable during sperm-oocyte fusion. Identification of mammalian orthologs
      that exhibit similar functions to these C. elegans genes has been a challenge.
      The mouse Izumo1 gene encodes a sperm-specific, immunoglobulin (Ig)-like
      transmembrane (TM) protein that is required for gamete fusion. We recently
      identified the C. elegans spe-45 gene, which shows male germline-enriched
      expression and encodes an Ig-like TM protein. spe-45 mutant worms produced
      otherwise normal spermatozoa that cannot fuse with oocytes, causing essentially
      the same phenotype as that seen in the Izumo1-knockout mice. By counting the
      number of self-sperm in the spermatheca of spe-45 hermaphrodites, it was found
      that this gene might be involved in sperm guidance from the uterus into the
      spermatheca, as well as gamete fusion. Moreover, we discovered that SPE-45 and
      IZUMO1 share certain functions for gamete fusion, which are presumably related to
      binding with cis- and/or trans-partners. Intriguingly, various organisms have Ig
      like TM proteins that act during gamete interactions, indicating the wide-spread
      utility of Ig-like domains during fertilization.

PMID- 27695653
TI  - Mechanism of chromatin segregation to the nuclear periphery in C. elegans
      embryos.
AB  - In eukaryotic organisms, gene regulation occurs in the context of chromatin. In
      the interphase nucleus, euchromatin and heterochromatin occupy distinct space
      during cell differentiation, with heterochromatin becoming enriched at the
      nuclear and nucleolar peripheries. This organization is thought to fine-tune gene
      expression. To elucidate the mechanisms that govern this level of genome
      organization, screens were carried out in C. elegans which monitored the loss of
      heterochromatin sequestration at the nuclear periphery. This led to the
      identification of a novel chromodomain protein, CEC-4 (Caenorhabditis elegans
      chromodomain protein 4) that mediates the anchoring of H3K9 methylation-bearing
      chromatin at the nuclear periphery in early to mid-stage embryos. Surprisingly,
      the loss of CEC-4 does not derepress genes found in heterochromatic domains, nor
      does it affect differentiation under standard laboratory conditions. On the other
      hand, CEC-4 contributes to the efficiency with which muscle differentiation is
      induced following ectopic expression of the master regulator, HLH-1. This is one
      of the first phenotypes specifically attributed to the ablation of
      heterochromatin anchoring.

PMID- 27695655
TI  - Probing and rearranging the transcription factor network controlling the C.
      elegans endoderm.
AB  - The ELT-2 GATA factor is the predominant transcription factor regulating gene
      expression in the C. elegans intestine, following endoderm specification. We
      comment on our previous study (Wiesenfahrt et al., 2016) that investigated how
      the elt-2 gene is controlled by END-1, END-3 and ELT-7, the 3 endoderm specific
      GATA factors that lie upstream in the regulatory hierarchy. We also discuss the
      unexpected result that ELT-2, if expressed sufficiently early and at sufficiently
      high levels, can specify the C. elegans endoderm, replacing the normal functions
      of END-1 and END-3.

PMID- 27695657
TI  - Cognitive Behavioral Therapy for Insomnia and Imagery Rehearsal in Combat
      Veterans with Comorbid Posttraumatic Stress: A Case Series.
AB  - Disrupted sleep is common among combat veterans and can negatively impact
      response to mental health treatments. A trial of cognitive behavioral therapy for
      insomnia (CBT-I) and imagery rehearsal therapy (IRT) for nightmares was conducted
      with 14 combat veterans diagnosed with insomnia, and who were experiencing
      posttraumatic stress and/or depression. In the case-series that follows veterans
      experienced clinically significant changes in sleep, and statistically
      significant reductions in insomnia, nightmare, depression and posttraumatic
      stress severity following treatment. Combined CBT-I and IRT is a promising
      treatment for patients with combat-related trauma and psychiatric morbidity.

PMID- 27695656
TI  - Leveraging the withered tail tip phenotype in C. elegans to identify proteins
      that influence membrane properties.
AB  - The properties of cellular membranes are critical for most cellular functions and
      are influenced by several parameters including phospholipid composition, integral
      and peripheral membrane proteins, and environmental conditions such as
      temperature. We previously showed that the C. elegans paqr-2 and iglr-2 mutants
      have a defect in membrane homeostasis and exhibit several distinct phenotypes,
      including a characteristic tail tip defect and cold intolerance. In the present
      study we report that screening for novel mutants with these 2 defects can lead to
      the identification of genes that are important contributors to membrane
      properties. In particular we isolated 3 novel alleles of sma-1, the C. elegans
      homolog of betaH spectrin, and 2 novel alleles of dpy-23, which encodes the C.
      elegans homolog of the AP2 MU subunit. We also show that sma-1 and dpy-23 act on
      membrane properties in pathways distinct from that of paqr-2 and iglr-2.

PMID- 27695658
TI  - Acetaminophen Use for Fever in Children Associated with Autism Spectrum Disorder.
AB  - Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social
      communication and restrictive behavior, interests, and activities. Our previous
      case-control study showed that use of acetaminophen at age 12-18 months is
      associated with increased likelihood for ASD (OR 8.37, 95% CI 2.08-33.7). In this
      study, we again show that acetaminophen use is associated with ASD (p = 0.013).
      Because these children are older than in our first study, the association is
      reversed; fewer children with ASD vs. non-ASD children use acetaminophen as a
      "first choice" compared to "never use" (OR 0.165, 95% CI 0.045, 0.599). We found
      significantly more children with ASD vs. non- ASD children change to the use of
      ibuprofen when acetaminophen is not effective at reducing fever (p = 0.033) and
      theorize this change in use is due to endocannabinoid system dysfunction. We also
      found that children with ASD vs. non-ASD children are significantly more likely
      to show an increase in sociability when they have a fever (p = 0.037) and
      theorize that this increase is due to anandamide activation of the
      endocannabinoid system in ASD children with low endocannabinoid tone from early
      acetaminophen use. In light of this we recommend that acetaminophen use be
      reviewed for safety in children.

PMID- 27695659
TI  - Connecting Gender, Race, Class, and Immigration Status to Disease Management at
      the Workplace.
AB  - OBJECTIVE: Chronic diseases are the leading causes of death in the United States.
      Chronic disease management occurs within all aspects of an individual's life,
      including the workplace. Though the social constructs of gender, race, class, and
      immigration status within the workplace have been considered, their connection to
      disease management among workers has been less explicitly explored. Using a
      sample of immigrant hotel housekeepers, we explored the connections between these
      four social constructs and hypertension management. METHODS: This qualitative
      research study was guided by critical ethnography methodology. Twenty-seven hotel
      room cleaners and four housemen were recruited (N = 31) and invited to discuss
      their experiences with hypertension and hypertension management within the
      context of their work environments. RESULTS: Being a woman worker within the
      hotel industry was perceived to negatively influence participants' experience
      with hypertension and hypertension management. In contrast, being a woman played
      a protective role outside the workplace. Being an immigrant played both a
      positive and a negative role in hypertension and its management. Being black and
      from a low socioeconomic class had only adverse influences on participants'
      experience with hypertension and its management. CONCLUSION: Being a woman,
      black, lower class, and an immigrant simultaneously contribute to immigrant hotel
      housekeepers' health and their ability to effectively manage their hypertension.
      The connection between these four constructs (gender, race, class, and
      immigration status) and disease management must be considered during care
      provision. Hotel employers and policy stakeholders need to consider those
      constructs and how they impact workers' well-being. More studies are needed to
      identify what mitigates the associations between the intersectionality of these
      constructs and immigrant workers' health and disease management within their work
      environment.

PMID- 27695660
TI  - Psychiatric Genetics in Child Custody Proceedings: Ethical, Legal, and Social
      Issues.
AB  - This paper considers the ethical, legal, and social issues raised by the prospect
      of increasing use of psychiatric genetic data in child custody litigation.
      Although genetic tests cannot currently confirm a parent or child's psychiatric
      diagnosis, it is likely that as relevant findings emerge, they will be introduced
      in family courts to challenge parental capacity. Here, we draw on three
      projected, but plausible, scenarios for obtaining psychiatric data about parents 
      - imposed genetic testing, access to medical records, and genetic theft -- then
      consider the use of psychiatric genetic data of children, to highlight the issues
      that judges, child custody evaluators, and clinicians who may provide treatment
      for parents or children with mental health issues will need to consider. These
      include: genetic privacy, stigma, genetic surveillance, and judicial and health
      professionals' bias. We argue that the unchecked introduction of psychiatric
      genetic data may have a detrimental effect on the administration of justice. In
      particular, the article highlights the risk that the (mis)use of psychiatric
      genetic data in custody disputes would 1) exacerbate stigma and treatment
      avoidance among parents and incentivize privacy violations to pressure parents to
      relinquish parental rights; 2) disproportionately affect poor parents and single
      mothers of color involved with Child Protective Services; and 3) detract
      attention from social and environmental factors impacting mental health to the
      detriment of the families involved. Awareness of these issues and an
      understanding of the meaning of genomic data by judges and custody evaluators
      will be pivotal in ensuring that justice is served.

PMID- 27695662
TI  - A Systematic Approach to Preclinical Trials in Metastatic Breast Cancer.
AB  - The process of developing new agents for therapy against breast cancer is
      inefficient and relies on animal models to screen for efficacy for preclinical
      studies. However, there has been limited validation of these models, despite the
      increasing costs in the rapidly growing era of personalized medicine and targeted
      therapy. Recently, there have been multiple studies which have critically
      evaluated animal models for breast cancer drug discovery. We recently reviewed
      the transgenic, xenograft, and syngeneic murine breast cancer models, the
      ectopic, orthotopic and intravenous methods of cell implantation, tumor gene
      expression profiles, as well as the ethics of animal experimentation, and we
      provide important information for investigators in this challenging field.
      Because of the complexities of treating breast cancer and the increasing costs of
      developing new agents, the choice of the appropriate murine model must carefully
      consider each model available, including the tumor gene expression profile. Such
      a critical approach to the in vivo portion of drug development will further
      increase the efficiency of breast cancer drug research and development.

PMID- 27695661
TI  - Staufen1s role as a splicing factor and a disease modifier in Myotonic Dystrophy
      Type I.
AB  - In a recent issue of PLOS Genetics, we reported that the double-stranded RNA
      binding protein, Staufen1, functions as a disease modifier in the neuromuscular
      disorder Myotonic Dystrophy Type I (DM1). In this work, we demonstrated that
      Staufen1 regulates the alternative splicing of exon 11 of the human Insulin
      Receptor, a highly studied missplicing event in DM1, through Alu elements located
      in an intronic region. Furthermore, we found that Staufen1 overexpression
      regulates numerous alternative splicing events, potentially resulting in both
      positive and negative effects in DM1. Here, we discuss our major findings and
      speculate on the details of the mechanisms by which Staufen1 could regulate
      alternative splicing, in both normal and DM1 conditions. Finally, we highlight
      the importance of disease modifiers, such as Staufen1, in the DM1 pathology in
      order to understand the complex disease phenotype and for future development of
      new therapeutic strategies.

PMID- 27695663
TI  - Adolescent Cellphone Use While Driving: An Overview of the Literature and
      Promising Future Directions for Prevention.
AB  - Motor vehicle crashes are the leading cause of death in adolescents, and drivers
      aged 16-19 are the most likely to die in distracted driving crashes. This paper
      provides an overview of the literature on adolescent cellphone use while driving,
      focusing on the crash risk, incidence, risk factors for engagement, and the
      effectiveness of current mitigation strategies. We conclude by discussing
      promising future approaches to prevent crashes related to cellphone use in
      adolescents. Handheld manipulation of the phone while driving has been shown to
      have a 3 to 4-fold increased risk of a near crash or crash, and eye glance
      duration greater than 2 seconds increases crash risk exponentially. Nearly half
      of U.S. high school students admit to texting while driving in the last month,
      but the frequency of use according to vehicle speed and high-risk situations
      remains unknown. Several risk factors are associated with cell phone use while
      driving including: parental cellphone use while driving, social norms for quick
      responses to text messages, and higher levels of temporal discounting. Given the
      limited effectiveness of current mitigation strategies such as educational
      campaigns and legal bans, a multi-pronged behavioral and technological approach
      addressing the above risk factors will be necessary to reduce this dangerous
      behavior in adolescents.

PMID- 27695664
TI  - I can't wait: Methods for measuring and moderating individual differences in
      impulsive choice.
AB  - Impulsive choice behavior occurs when individuals make choices without regard for
      future consequences. This behavior is often maladaptive and is a common symptom
      in many disorders, including drug abuse, compulsive gambling, and obesity.
      Several proposed mechanisms may influence impulsive choice behavior. These
      mechanisms provide a variety of pathways that may provide the basis for
      individual differences that are often evident when measuring choice behavior.
      This review provides an overview of these different pathways to impulsive choice,
      and the behavioral intervention strategies being developed to moderate impulsive
      choice. Because of the compelling link between impulsive choice behavior and the
      near-epidemic pervasiveness of obesity in the United States, we focus on the
      relationship between impulsive choice behavior and obesity as a test case for
      application of the multiple pathways approach. Choosing immediate gratification
      over healthier long term food choices is a contributing factor to the obesity
      crisis. Behavioral interventions can lead to more self controlled choices in a
      rat pre-clinical model, suggesting a possible gateway for translation to human
      populations. Designing and implementing effective impulsive choice interventions
      is crucial to improving the overall health and well-being of impulsive
      individuals.

PMID- 27695665
TI  - Alexithymia and Addiction: A Review and Preliminary Data Suggesting
      Neurobiological Links to Reward/Loss Processing.
AB  - Alexithymia, characterized by impairments in emotional awareness, is common among
      individuals with substance use disorders. Research on alexithymia suggests that
      it is a trait that may contribute to substance dependence. This paper will review
      alexithymia as it relates to substance use and substance use disorders,
      considering its potential role in the maintenance and treatment of these
      disorders. We will then describe how neural correlates associated with
      alexithymia may shed light on how alexithymia relates to addiction. Finally, we
      present preliminary fMRI data that examines how alexithymia may relate to the
      neurobiological correlates of reward/loss processing in individuals with cocaine
      dependence. While preliminary, these findings suggest a role of alexithymia in
      reward anticipation in cocaine-dependent individuals.

PMID- 27695667
TI  - Deceleration of probe beam by stage bias potential improves resolution of serial
      block-face scanning electron microscopic images.
AB  - Serial block-face scanning electron microscopy (SBEM) is quickly becoming an
      important imaging tool to explore three-dimensional biological structure across
      spatial scales. At probe-beam-electron energies of 2.0 keV or lower, the axial
      resolution should improve, because there is less primary electron penetration
      into the block face. More specifically, at these lower energies, the interaction
      volume is much smaller, and therefore, surface detail is more highly resolved.
      However, the backscattered electron yield for metal contrast agents and the
      backscattered electron detector sensitivity are both sub-optimal at these lower
      energies, thus negating the gain in axial resolution. We found that the
      application of a negative voltage (reversal potential) applied to a modified SBEM
      stage creates a tunable electric field at the sample. This field can be used to
      decrease the probe-beam-landing energy and, at the same time, alter the
      trajectory of the signal to increase the signal collected by the detector. With
      decelerated low landing-energy electrons, we observed that the probe-beam
      electron-penetration depth was reduced to less than 30 nm in epoxy-embedded
      biological specimens. Concurrently, a large increase in recorded signal occurred
      due to the re-acceleration of BSEs in the bias field towards the objective pole
      piece where the detector is located. By tuning the bias field, we were able to
      manipulate the trajectories of the  primary and secondary electrons, enabling the
      spatial discrimination of these signals using an advanced ring-type BSE detector
      configuration or a standard monolithic BSE detector coupled with a blocking
      aperture.

PMID- 27695666
TI  - The Neurobiological Basis for Social Affiliation in Autism Spectrum Disorder and
      Schizophrenia.
AB  - Social interaction and communication are complex behavioral paradigms involving
      many components. Many different neurotransmitters, hormones, sensory inputs, and
      brain regions are involved in the act of social engagement and verbal or
      nonverbal communication. Autism Spectrum Disorder (ASD) and schizophrenia are two
      neurodevelopmental disorders that have social and language deficits as hallmark
      symptoms, but show very different etiologies. The output of social dysfunction is
      common to both ASD and schizophrenia, but this likely arises from very different
      pathophysiological means. This review will attempt to compile and interpret human
      and animal studies showing the neurobiological basis for the development of
      social and language deficits in ASD and schizophrenia as well as a comparison of
      the two disorders.

PMID- 27695668
TI  - The association between maternal nutrition and lifestyle during pregnancy and 2
      year-old offspring adiposity: analysis from the ROLO study.
AB  - AIM: To examine the association between maternal nutrition and lifestyle factors
      and offspring adiposity, using baseline and 2-year postpartum follow-up data from
      a randomised control trial of low glycaemic index diet. SUBJECT AND METHODS: Food
      diaries and lifestyle questionnaires were completed during pregnancy and infant
      feeding and maternal lifestyle questionnaires 2 years postpartum for 281 mother
      and infant pairs from the ROLO study. Maternal anthropometry was measured
      throughout pregnancy and infant and maternal anthropometry was measured 2 years
      postpartum. RESULTS: Maternal 2 year postpartum body mass index (BMI) was
      positively associated with offspring BMI-for-age z-score (B = 0.105, p = 0.015).
      Trimester 2 saturated fat intake was positively associated with offspring
      subscapular:triceps skinfold ratio (B = 0.018, p = 0.001). Trimester 1 glycaemic
      index was also positively associated with offspring sum of subscapular and
      triceps skinfolds (B = 0.009, p = 0.029). CONCLUSIONS: Maternal BMI 2 years
      postpartum was positively associated with offspring BMI. Pregnancy saturated fat
      intake was positively and polyunsaturated fat negatively associated with
      offspring adiposity. While further research is necessary, pregnancy and the
      postpartum period may be early opportunities to combat childhood obesity.

PMID- 27695669
TI  - Environmental determinants of aplastic anemia in Pakistan: a case-control study.
AB  - AIM: Aplastic anemia (AA) affects the Asian population two to three fold more
      than people in other regions. Besides the host genetics and socioeconomic status,
      several other environmental exposures have been linked with an AA etiology. We
      aimed to examine the association of various environmental exposures with AA
      occurrence among Pakistani individuals. SUBJECTS AND METHODS: A case-control
      study was conducted in Karachi, Pakistan, where cases (diagnosed AA patients)
      were selected from the National Institute of Blood Disease and Bone Marrow
      Transplantation (NIBD), while for each case, a single control (who was free of AA
      and visited the outpatient department of the same hospital for the treatment of
      minor ailments) was selected matched by age and sex. A total of 428 participants
      were included in this study with equal proportions of cases and controls.
      Information related to disease characteristics, sociodemographics and exposure to
      chemicals was collected through a survey questionnaire, laboratory investigations
      and medical records. Descriptive results were reported as frequencies and
      proportions, adjusted odds ratios with 95 % confidence intervals and population
      attributable risk (PAR) as percentage. RESULTS: Among study participants (n =
      428), AA was significantly associated with various environmental exposures.
      Participants residing in rural settings (OR = 2.29, 95 % CI 1.12-4.67, p-value <
      0.01) and those who reported exposure to pesticides (OR = 3.58, 95 % CI 1.27
      10.10, p-value 0.01; PAR = 18.16 %) were significantly more likely to report AA.
      Participants with a formal education were significantly less likely to have AA
      (OR = 0.27, 95 % CI 0.10-0.71, p-value < 0.01). CONCLUSIONS: This study observed
      a significant association of aplastic anemia with a lower socioeconomic profile,
      and certain environmental exposures among the Pakistani population. The evidence
      may be helpful in understanding the pathophysiology of aplastic anemia in the
      context of environmental exposures.

PMID- 27695670
TI  - Prognostic significance of novel katG mutations in Mycobacterium tuberculosis.
AB  - BACKGROUND: By using whole genome sequencing (WGS), researchers are beginning to
      understand the genetic diversity of Mycobacterium tuberculosis (MTB) and its
      consequences for the diagnosis of multidrug-resistant tuberculosis (MDR-TB) on a
      genomic scale. The Global Consortium for Drug-resistant TB Diagnostics (GCDD)
      conducted a genome scale variant analyses of 366 clinical MTB genomes (mostly
      MDR/XDR [extensively drug resistant]) from four countries in order to inform the
      development of rapid molecular diagnostics. This project has been extended by
      performing an evolutionary analysis of isoniazid (INH)-resistant isolates for
      prognostic purposes. METHODS: 151 (130 INHR, 21 INHS) clinical MTB isolates from
      India (19: 17 INHR, 2 INHS), Moldova (48: 42 INHR, 6 INHS), the Philippines (26:
      20 INHR, 6 INHS), and South Africa (58: 51 INHR, 7 INHS) were included in this
      study. INH drug susceptibility was determined by using MGIT 960 and WHO (World
      Health Organization)-recommended critical concentration of 0.1 mg/L. Isolates
      were sequenced using PacBio RS WGS platform. A genome-wide variant analysis was
      conducted using a proprietary pipeline (PacDAP) developed at San Diego State
      University. To infer the amino acid changes in katG that confer resistance, PAML
      was utilized to detect sites in silico that are under positive selection. The
      dN/dS method was used in combination with Bayes empirical Bayes to determine
      sites under positive selection and Chi-Squared analysis to determine the
      significance of the selected sites. RESULTS: PacDAP variant analysis revealed 22
      novel catalase-peroxidase (katG product) mutations. Of these, 14 were single
      nucleotide polymorphisms, while 8 novel mutations appeared in combination with
      katG S315T and/or with inhA promoter C-15T. These SNPs have not been previously
      reported. Additionally, 11 previously observed, but uncommon, katG mutations were
      also observed in these clinical isolates. These results suggest that 17 amino
      acids in the enzyme are under positive selective pressure; most significantly in
      South Africa and the Philippines. No selective pressure on codons other than 315
      was observed in isolates from Moldova. Due to the low number of isolates from
      India, the significance of the sites under positive selection was low and no
      prediction for India could be made based on this study. CONCLUSIONS: Eleven of
      the 14 SNPs are resistance conferring, and it is believed that the remaining 8
      combinatorial mutations are either compensatory in nature or, in combination with
      known SNPs, could increase resistance levels. Positive selection results indicate
      a diversifying evolutionary path to resistance more in line with long tail
      statistics and therefore indicate a departure from the traditional point mutation
      (or "hotspot") model that current molecular diagnostics are based on. Positive
      selection pressures indicate a future with elevated diagnostic and prognostic
      significance of the "long tail" (i.e., alternative mechanisms of resistance) and
      potentially diminishing significance of the canonical mutations (especially in
      South Africa and the Philippines), which could have significant future
      implications on narrowly targeting molecular diagnostics.

PMID- 27695672
TI  - Enriched surface acidity for surfactant-free suspensions of carboxylated carbon
      nanotubes purified by centrifugation.
AB  - It is well known that surfactant-suspended carbon nanotube (CNT) samples can be
      purified by centrifugation to decrease agglomerates and increase individually
      dispersed CNTs. However, centrifugation is not always part of protocols to
      prepare CNT samples used in biomedical applications. Herein, using carboxylated
      multi-walled CNTs (cMWCNTs) suspended in water without a surfactant, we developed
      a Boehm titrimetric method for the analysis of centrifuged cMWCNT suspensions and
      used it to show that the surface acidity of oxidized carbon materials in aqueous
      cMWCNT suspensions was enriched by ~40% by a single low-speed centrifugation
      step. This significant difference in surface acidity between un-centrifuged and
      centrifuged cMWCNT suspensions has not been previously appreciated and is
      important because the degree of surface acidity is known to affect the
      interactions of cMWCNTs with biological systems.

PMID- 27695673
TI  - Extensive subclinical sinusitis leading to Moraxella osloensis meningitis.
AB  - We report a case of a 31 year old male with extensive subclinical sinusitis
      leading to erosion in the cribriform plate and subsequent meningitis caused by
      the organism Moraxella osloensis. The patient presented to the emergency
      department with rapid onset confusion, neck stiffness and headache. Inflammatory
      markers, renal and liver function, and a chest radiograph were all normal. CT
      Head showed extensive polyp disease in the paranasal sinuses with expansion of
      the left frontal sinus and CT Sinuses revealed an area of low attenuation in the
      cribriform plate consistent with bony erosion. MRI Head showed thick loculated
      sinus inflammation. Lumbar puncture yielded CSF with a high white cell count of
      predominantly mononuclear cells, no visible organisms and an elevated protein.
      CSF microscopy, culture and viral PCR were not diagnostic, and so the CSF was
      sent for 16S rDNA PCR screening, which identified the rDNA of Moraxella
      osloensis. Moraxella osloensis is a rare cause of bacterial meningitis, with only
      a few reported cases. This case illustrates that sinusitis, while a common
      condition, when severe can predispose to intracranial infection with atypical and
      low virulence organisms such as Moraxella species, which do not commonly cause
      invasive CNS disease. This case represents the first case of Moraxella osloensis
      meningitis reported from the United Kingdom.

PMID- 27695671
TI  - Similarities and differences in coatings for magnesium-based stents and
      orthopaedic implants.
AB  - Magnesium (Mg)-based biodegradable materials are promising candidates for the new
      generation of implantable medical devices, particularly cardiovascular stents and
      orthopaedic implants. Mg-based cardiovascular stents represent the most
      innovative stent technology to date. However, these products still do not fully
      meet clinical requirements with regards to fast degradation rates, late
      restenosis, and thrombosis. Thus various surface coatings have been introduced to
      protect Mg-based stents from rapid corrosion and to improve biocompatibility.
      Similarly, different coatings have been used for orthopaedic implants, e.g.,
      plates and pins for bone fracture fixation or as an interference screw for tendon
      bone or ligament-bone insertion, to improve biocompatibility and corrosion
      resistance. Metal coatings, nanoporous inorganic coatings and permanent polymers
      have been proved to enhance corrosion resistance; however, inflammation and
      foreign body reactions have also been reported. By contrast, biodegradable
      polymers are more biocompatible in general and are favoured over permanent
      materials. Drugs are also loaded with biodegradable polymers to improve their
      performance. The key similarities and differences in coatings for Mg-based stents
      and orthopaedic implants are summarized.

PMID- 27695674
TI  - Characteristics of mucoid Streptococcus pyogenes isolated from two patients with
      pneumonia in a local community.
AB  - Streptococcus pyogenes (Group A Streptococcus, GAS) infections can develop into
      life-threatening disorders. However, the occurrence of some GAS pneumonia cases
      is relatively rare in a local community. We report here characteristics of mucoid
      GAS isolates obtained from the sputum of two patients with pneumonia in a local
      community. Although case-patients did not have contact with each other, case
      patient 1's child and case-patient 2's grandchild attended the same kindergarten
      where a GAS pharyngitis epidemic had occurred. We conducted phenotypic and
      genotypic analyses with the GAS isolates from sputum of both patients, to examine
      (1) colony appearance between the isolates, (2) numerical profile based on API-20
      Strep system, (3) similarity to the type strain using 16S rRNA sequencing, (4)
      emm type (subtype) and emm full-length sequence, (5) sequence type, (6) sic
      allele, (7) antimicrobial susceptibility result and the resistance determinant,
      (8) genome profile following a random amplified polymorphic DNA fragments, and
      (9) pattern of digested DNA fragments by pulse-field gel electrophoresis. These
      phenotypic and genotypic analyses revealed similar matching between the isolates
      from both cases. Our findings suggest that when clinicians examine adult patients
      having infection with the mucoid GAS, they should confirm whether anyone within
      the same household also developed the infection and need to investigate epidemic
      situations in local communities, including kindergartens and elementary schools.

PMID- 27695676
TI  - Can antiretrovirals curb southern Africa's HIV-associated TB epidemic?

PMID- 27695675
TI  - Theory of Mind, Emotion Recognition and Social Perception in Individuals at
      Clinical High Risk for Psychosis: findings from the NAPLS-2 cohort.
AB  - Social cognition, the mental operations that underlie social interactions, is a
      major construct to investigate in schizophrenia. Impairments in social cognition
      are present before the onset of psychosis, and even in unaffected first-degree
      relatives, suggesting that social cognition may be a trait marker of the illness.
      In a large cohort of individuals at clinical high risk for psychosis (CHR) and
      healthy controls, three domains of social cognition (theory of mind, facial
      emotion recognition and social perception) were assessed to clarify which domains
      are impaired in this population. Six-hundred and seventy-five CHR individuals and
      264 controls, who were part of the multi-site North American Prodromal
      Longitudinal Study, completed The Awareness of Social Inference Test, the Penn
      Emotion Recognition task, the Penn Emotion Differentiation task, and the
      Relationship Across Domains, measures of theory of mind, facial emotion
      recognition, and social perception, respectively. Social cognition was not
      related to positive and negative symptom severity, but was associated with age
      and IQ. CHR individuals demonstrated poorer performance on all measures of social
      cognition. However, after controlling for age and IQ, the group differences
      remained significant for measures of theory of mind and social perception, but
      not for facial emotion recognition. Theory of mind and social perception are
      impaired in individuals at CHR for psychosis. Age and IQ seem to play an
      important role in the arising of deficits in facial affect recognition. Future
      studies should examine the stability of social cognition deficits over time and
      their role, if any, in the development of psychosis.

PMID- 27695677
TI  - Highlighting the need for more infection control practitioners in low- and middle
      income countries.
AB  - Background: Many low- and middle-income countries struggle to implement, monitor
      and evaluate the efficacy of infection control (IC) measures within health care
      facilities. This hampers their ability to prevent nosocomial infections, identify
      emerging pathogens and rapidly alert officials to possible outbreaks. The lack of
      dedicated and trained IC practitioners (ICPs) is a serious deficit in the health
      care workforce, and is worsened by the lack of institutions that offer IC
      training. Discussion: While no single individual can entirely eliminate the risk
      of nosocomial transmission, there is literature to support the value of
      designated IC persons. Recommendations from the World Health Organization in 2008
      and 2009 describe the need for this specialized cadre of workers, but many
      countries lack the national regulations to authorize, train and manage such
      professionals at the national or local level. This article provides an overview
      of how ICPs are trained and credentialed in several countries, and discusses
      approaches countries can use to train ICPs. Conclusion: Trained ICPs can help
      prevent future outbreaks and control nosocomial transmission of diseases in
      health care facilities. For this to occur, supportive national policies,
      availability of training institutions and local administrative support will be
      required.

PMID- 27695678
TI  - Declining tuberculosis case notification rates with the scale-up of
      antiretroviral therapy in Zimbabwe.
AB  - Setting: Zimbabwe has a human immunodeficiency virus (HIV) driven tuberculosis
      (TB) epidemic, with antiretroviral therapy (ART) scaled up in the public sector
      since 2004. Objective: To determine whether national ART scale-up was associated
      with annual national TB case notification rates (CNR), stratified by disease type
      and category, between 2000 and 2013. Design: This was a retrospective study using
      aggregate data from global reports. Results: The number of people living with HIV
      and retained on ART from 2004 to 2013 increased from 8400 to 665 299, with ART
      coverage increasing from <0.5% to 48%. TB CNRs, all types and categories,
      increased from 2000 to 2003, and declined thereafter from 2004 to 2013. The
      decreases in annual TB notifications between the highest rates (before 2004) and
      lowest rates (2013) were all forms of TB (56%), new TB (60%), previously treated
      TB (53%), new smear-positive pulmonary TB (PTB) (40%), new smear-negative/smear
      unknown PTB (58%) and extra-pulmonary TB (58%). Conclusion: Significant declines
      in TB CNRs were observed during ART scale-up, especially for smear-negative PTB
      and extra-pulmonary TB. These encouraging national trends support the continued
      scale-up of ART for people living with HIV as a way of tackling the twin
      epidemics of HIV/acquired immune-deficiency syndrome and TB in Zimbabwe.

PMID- 27695680
TI  - Did FIDELIS projects contribute to the detection of new smear-positive pulmonary
      tuberculosis cases in China?
AB  - Setting: The first phase of the Fund for Innovative DOTS Expansion through Local
      Initiatives to Stop TB (FIDELIS) projects in China started in 2003. Objective: To
      determine whether the FIDELIS projects contributed to the increased case
      detection rate for new smear-positive pulmonary tuberculosis (PTB) in China.
      Methods: We compared the case notification rates (CNRs) in the intervention year
      with those of the previous year in the FIDELIS areas, then compared the
      difference between the CNRs of the intervention year and the previous year in the
      FIDELIS areas with those in the non-FI-DELIS areas within the province. Results:
      There was an increase in the CNR in the intervention year compared with the
      previous year for all the project sites. The differences between the CNR in the
      intervention year and the previous year ranged from 6.4 to 31.1 per 100 000
      population in the FIDELIS areas and from 2.9 to 20.4/100 000 in the non-FIDELIS
      areas. Differences-in-differences analysis shows that the differences in the CNRs
      in the FIDELIS areas were not statistically significantly different from those in
      the non-FIDELIS areas (P = 0.393). Conclusion: The FIDELIS projects may have
      contributed to the increase in case detection of new smear-positive PTB in China,
      but the level of evidence is low.

PMID- 27695679
TI  - Dotting the Three I's for collaborative TB-HIV activities: evaluation of a pilot
      programme in Kathmandu, Nepal.
AB  - Setting: The three government tertiary care hospitals providing care for people
      living with the human immunodeficiency virus (PLHIV) in Kathmandu, Nepal.
      Objectives: To assess 1) the screening cascades for intensified case finding for
      tuberculosis (TB), 2) isoniazid preventive therapy (IPT), including demographic
      and clinical factors associated with treatment interruption, and 3) TB infection
      control (IC) in the health facilities. Design: A cross-sectional study of new
      PLHIV enrolled from January 2012 to December 2014. Results: Among 572 registered
      PLHIV, 91% were on antiretroviral therapy. Of those registered, 561 (98%) were
      screened for TB and 73 (13%) were diagnosed with TB (17 [25%] sputum smear
      positive, 17 [25%] smear-negative and 35 [51%] extra-pulmonary). Among the 488
      (87%) PLHIV without active TB, 157 (32%) were initiated on IPT, of whom 136 (87%)
      completed treatment and 17 (11%) interrupted treatment. Those who experienced
      adverse events were 12 times more likely to interrupt IPT. TB IC showed gaps in
      personal control measures and supporting structures and policies. Conclusion: The
      implementation of the Three I's for collaborative TB-HIV activities in pilot
      sites in Nepal was successful and should be scaled up.

PMID- 27695681
TI  - Health service perceptions about implementation of a new TB diagnostic in
      Northern Russia: a qualitative study.
AB  - Setting: Many tuberculosis services are implementing new diagnostics to
      accelerate treatment initiation for multidrug-resistant tuberculosis. Successful
      implementation and uptake are likely to depend on many factors. Objective: To
      describe the perceptions of the Arkhangelsk health services staff in Northern
      Russia on the process of introducing the line-probe assay and to determine what
      facilitates the process of uptake into practice. Design: Process evaluation; semi
      structured, in-depth interviews with key informants from civil and penitentiary
      health services; content analysis. Results: A good working relationship between
      the civil and penitentiary sectors and a tradition of positive collaboration
      between doctors and managers were integral to success. Uptake and adaptation were
      facilitated by regular discussions between managers and implementers, flexibility
      in adapting routines and an iterative approach to improving procedures. It is
      beneficial to allow all types of health care workers affected by the diagnostic
      to learn about it and contribute to its integration. A multidisciplinary
      evaluation can detect problems elsewhere in the care pathway. Bringing about
      change in workplace mind-sets and attitudes takes time and management.
      Conclusion: People take time to observe the effects of innovations, assess
      relative advantages and become convinced, sometimes by different types of
      evidence. Multi-disciplinary opportunities for learning, reflecting on care
      pathways and adaptation should all be a part of introducing new diagnostics.

PMID- 27695682
TI  - The experience of bedaquiline implementation at a decentralised clinic in South
      Africa.
AB  - Multidrug-resistant tuberculosis (MDR-TB) is a serious public health problem, but
      the new drugs bedaquiline (BDQ) and delamanid offer hope to improve outcomes and
      minimise toxicity. In Khayelitsha, South Africa, patients are routinely started
      on BDQ in the out-patient setting. This report from the field describes BDQ use
      in the out-patient setting at the Nolungile Clinic. The clinic staff overall
      report a positive experience using the drug. Challenges have been based largely
      on the logistics of drug supply and delivery. BDQ can be started successfully in
      the out-patient setting, and can be a positive experience for both patients and
      providers. La tuberculose multiresistante (TB-MDR) est un probleme de sante
      publique grave, mais les nouveaux medicaments que sont la bedaquiline (BDQ) et le
      delamanide apportent un espoir d'ameliorer les resultats tout en reduisant la
      toxicite. A Khayelitsha, Afrique du Sud, les patients demarrent leur traitement
      par BDQ en consultation externe en routine. Ce rapport du terrain decrit
      l'utilisation de la BDQ a la consultation externe du dispensaire Nolungile. Dans
      l'ensemble, le personnel du centre de sante exprime une experience positive du
      medicament. Les defis ont surtout ete lies a la logistique de l'approvisionnement
      et de la distribution du medicament. La BDQ peut etre mise en route avec succes
      dans le cadre d'une consultation externe et peut constituer une experience
      positive pour les patients et les prestataires de soins. La tuberculosis
      multirresistente (TB-MDR) representa un grave problema de salud publica, pero la
      utilizacion de nuevos medicamentos como la bedaquilina (BDQ) y el delamanid
      ofrece perspectivas de mejores desenlaces terapeuticos y disminucion de la
      toxicidad asociada. En Khayelitsha, Surafrica, se inicia de manera sistematica el
      tratamiento ambulatorio con BDQ. En el presente informe del terreno, se describe
      la utilizacion de BDQ en tratamiento antituberculoso ambulatorio en el centro de
      atencion Nolungile. En general, los miembros del personal del centro refirieron
      una experiencia positiva con la administracion del medicamento. Las dificultades
      surgieron en gran parte con respecto a aspectos logisticos del suministro y la
      administracion del medicamento. Es posible iniciar un tratamiento eficaz con BDQ
      en condiciones ambulatorias, y represente una experiencia positiva para los
      pacientes y los profesionales de salud.

PMID- 27695683
TI  - Surgical interventions for pulmonary tuberculosis in Mumbai, India: surgical
      outcomes and programmatic challenges.
AB  - Setting: While surgery for pulmonary tuberculosis (PTB) is considered an
      important adjunct for specific cases, including drug-resistant tuberculosis,
      operational evidence on its feasibility and effectiveness is limited. Objective:
      To describe surgical outcomes and programmatic challenges of providing surgery
      for PTB in Mumbai, India. Design: A descriptive study of routinely collected data
      of surgical interventions for PTB from 2010 to 2014 in two Mumbai hospitals, one
      public, one private. Results: Of 85 patients, 5 (6%) died and 17 (20%) had
      complications, with wound infection being the most frequent. Repeat operation was
      required in 12 (14%) patients. Most procedures were performed on an emergency
      basis, and eligibility was established late in the course of treatment. Median
      time from admission to surgery was 51 days. Drug susceptibility test (DST)
      patterns and final treatment outcomes were not systematically collected.
      Conclusion: In a high-burden setting such as Mumbai, important data on surgery
      for PTB were surprisingly limited in both the private and public sectors.
      Eligibility for surgery was established late, culture and DST were not
      systematically offered, the interval between admission and surgery was long and
      TB outcomes were not known. Systematic data collection would allow for proper
      evaluation of surgery as adjunctive therapy for all forms of TB under
      programmatic conditions.

PMID- 27695684
TI  - Chronic respiratory disease in adults treated for tuberculosis in Khartoum,
      Sudan.
AB  - Background: Chronic respiratory disease (CRD) causes substantial morbidity and
      mortality. Although the global CRD epidemic collides with the tuberculosis (TB)
      epidemic in many low- and middle-income country settings, the risk of TB
      associated CRD is not well described in countries with a high burden of TB.
      Methods: We recruited 136 patients with a history of sputum smear-positive
      pulmonary TB (PTB) from the TB clinic at Omdurman Teaching Hospital in Khartoum,
      Sudan, and 136 age- and sex-matched community controls, between 28 July 2013 and
      30 December 2013. Data were collected using standardised questionnaires and
      spirometry was performed before and after bronchodilator. Results: The mean age
      of the subjects with previous PTB and controls was respectively 44.0 years (SD
      8.5) and 44.5 years (SD 8.6), with 27.2% females in both groups. Chronic
      respiratory symptoms such as chronic cough (OR 6.67, 95%CI 2.98-14.90, P < 0.001)
      and the presence of chronic airflow obstruction (OR 12.4, 95%CI 1.56-98.40, P =
      0.02) were both strongly associated with a past history of PTB after adjusting
      for potential confounders. Conclusion: The clinical features of CRDs are strongly
      associated with past history of PTB. An integrated approach to improve the
      management of these common conditions should be considered. Contexte : Les
      maladies respiratoires chroniques (MRC) sont a l'origine d'une morbidite et d'une
      mortalite considerables dans le monde. Bien que l'epidemie mondiale des MRC entre
      en conflit avec l'epidemie de tuberculose (TB) dans de nombreux pays a revenu
      faible ou moyen, le risque de MRC associee a la TB n'est pas bien decrit dans les
      pays durement frappes par la TB. Methodes : Nous avons recrute 136 patients ayant
      des antecedents de tuberculose pulmonaire (TBP) a frottis positif dans le service
      de pneumologie du Centre Hospitalier Universitaire Omdurman a Khartoum, Soudan,
      et 136 temoins de la communaute, apparies sur l'age et le sexe, entre le 28
      juillet 2013 et le 30 decembre 2013. Les donnees ont ete recueillies grace a des
      questionnaires standardises ainsi qu'a une spirometrie avant et apres
      bronchodilatateur. Resultats : L'age moyen des cas et des temoins a ete de 44,0
      ans (DS 8,5) et 44,5 ans (DS 8,61), respectivement, avec 27,2% de femmes dans les
      deux groupes. Des symptomes respiratoires chroniques comme une toux chronique (OR
      6,67 ; IC95% 2,98-14,90 ; P < 0,001) et la presence d'une obstruction chronique
      des voies aeriennes (OR 12,39 ; IC%95 1,56-98,40 ; P = 0,02) ont ete tous deux
      fortement associes a des antecedents de TBP apres ajustement sur les facteurs de
      confusion potentiels. Conclusion : Les caracteristiques cliniques des MRC sont
      fortement associees a des antecedents de TBP. Une approche integree visant a
      ameliorer la prise en charge de ces pathologies frequentes devrait etre
      envisagee. Marco de referencia: La enfermedad pulmonar cronica (EPC) es una causa
      importante de morbilidad y mortalidad. Aunque la epidemia mundial de EPC rivaliza
      con la epidemia de tuberculosis (TB) en muchos entornos de paises con bajos y
      medianos recursos, el riesgo de aparicion de EPC asociado con la TB se ha
      descrito cabalmente en los paises con una alta carga de morbilidad por TB.
      Metodos: Entre el 28 de julio y el 30 de diciembre del 2013, participaron en el
      estudio 136 pacientes con antecedente de tuberculosis pulmonar (TBP) y
      baciloscopia positiva del esputo que habian recibido tratamiento en el
      consultorio de neumologia del Hospital Universitario Omdurman de Jartun, en
      Sudan, y 136 testigos sanos de la comunidad, emparejados en funcion de la edad y
      el sexo. Se recogieron datos mediante cuestionarios normalizados y se practico
      una espirometria antes y despues una prueba de broncodilatacion. Resultados: El
      promedio de la edad en el grupo de los casos fue 44,0 (desviacion estandar 8,5
      anos) y en el grupo de testigos fue 44,5 anos (8,6 anos); la proporcion de
      mujeres en ambos grupos fue 27,2%. Se observo una fuerte asociacion entre la
      presencia de sintomas respiratorios cronicos como la tos (OR 6,67; IC95% 2,98
      14,90; P < 0,001) y la presencia de obstruccion cronica al flujo en las vias
      respiratorias (OR 12,39; IC95% 1,56-98,40; P = 0,02) en las personas con
      antecedente de TBP, una vez corregidos los posibles factores de confusion.
      Conclusion: La presencia de rasgos clinicos de EPC exhibe una fuerte correlacion
      con el antecedente de TBP. Es preciso considerar la posibilidad de aplicar un
      enfoque integrado con el fin de mejorar la atencion de ambas enfermedades tan
      frecuentes.

PMID- 27695685
TI  - Karnataka state in India set to remove unqualified health providers from its
      health care system.

PMID- 27695686
TI  - India's new TB diagnostic algorithm - far from reality?

PMID- 27695687
TI  - Sustained research capacity after completing a Structured Operational Research
      and Training (SORT IT) course.

PMID- 27695688
TI  - Assistive Technology Needs and Measurement of the Psychosocial Impact of
      Assistive Technologies for Independent Living of Older Hispanics: Lessons
      Learned.
AB  - (1) Knowledge about the assistive technology (AT) needs and psychosocial impact
      of AT in different populations is needed because the adoption, retention, or
      abandonment of AT may be influenced by the psychosocial impact that AT has on its
      users. The aims of this study were to: (a) identify the AT needs of a sample of
      Hispanic older adults with functional limitations, (b) describe the psychosocial
      impact of these technologies on the sample's quality of life, and (c) describe
      the methodological challenges in using the Puerto Rican version of the
      Psychosocial Impact of Assistive Device Scale (PR-PIADS) with a Hispanic sample.
      (2) Methods: This study used a cross-sectional design conducted with a sample of
      60 participants. Data was collected using the Assistive Technology Card
      Assessment Questionnaire (ATCAQ) and the PR-PIADS. Data analyses included
      descriptive statistics and bivariate analysis. (3) Results: The sample's most
      frequently reported needs for AT devices were in the areas of cooking, home
      tasks, and home safety activities. The sample reported a positive impact of AT
      use in their quality of life. Several methodological challenges of the PIADS were
      identified. (4) Conclusions: The sample has unmet needs for using AT devices to
      overcome difficulties in daily living activities.

PMID- 27695689
TI  - Tick Genome Assembled: New Opportunities for Research on Tick-Host-Pathogen
      Interactions.
AB  - As tick-borne diseases are on the rise, an international effort resulted in the
      sequence and assembly of the first genome of a tick vector. This result promotes
      research on comparative, functional and evolutionary genomics and the study of
      tick-host-pathogen interactions to improve human, animal and ecosystem health on
      a global scale.

PMID- 27695690
TI  - Correlation of Antagonistic Regulation of leuO Transcription with the Cellular
      Levels of BglJ-RcsB and LeuO in Escherichia coli.
AB  - LeuO is a conserved and pleiotropic transcription regulator, antagonist of the
      nucleoid-associated silencer protein H-NS, and important for pathogenicity and
      multidrug resistance in Enterobacteriaceae. Regulation of transcription of the
      leuO gene is complex. It is silenced by H-NS and its paralog StpA, and it is
      autoregulated. In addition, in Escherichia coli leuO is antagonistically
      regulated by the heterodimeric transcription regulator BglJ-RcsB and by LeuO.
      BglJ-RcsB activates leuO, while LeuO inhibits activation by BglJ-RcsB.
      Furthermore, LeuO activates expression of bglJ, which is likewise H-NS repressed.
      Mutual activation of leuO and bglJ resembles a double-positive feedback network,
      which theoretically can result in bi-stability and heterogeneity, or be
      maintained in a stable OFF or ON states by an additional signal. Here we
      performed quantitative and single-cell expression analyses to address the
      antagonistic regulation and feedback control of leuO transcription by BglJ-RcsB
      and LeuO using a leuO promoter mVenus reporter fusion and finely tunable bglJ and
      leuO expression plasmids. The data revealed uniform regulation of leuO expression
      in the population that correlates with the relative cellular concentration of
      BglJ and LeuO. The data are in agreement with a straightforward model of
      antagonistic regulation of leuO expression by the two regulators, LeuO and BglJ
      RcsB, by independent mechanisms. Further, the data suggest that at standard
      laboratory growth conditions feedback regulation of leuO is of minor relevance
      and that silencing of leuO and bglJ by H-NS (and StpA) keeps these loci in the
      OFF state.

PMID- 27695691
TI  - Xanthogranulomatous prostatitis with prostato-rectal fistula: a case report and
      review of the literature.
AB  - PURPOSE: Xanthogranulomatous prostatitis (XP) is a rare form of nonspecific
      granulomatous prostatitis that can clinically mimic high-grade prostatic
      carcinoma. It is difficult to diagnose it definitely in clinical settings.
      METHODS: We report a case of XP with prostate-rectal fistula and review the
      relevant literatures. RESULT: A 75-year-old man presented with rectal bleeding
      when he urinated. A locally advanced carcinoma of prostate was suspected
      initially following the physical, imaging, and hematologic examinations.
      Subsequently on histopathological and immunohistochemical staining after needle
      biopsy of the prostate, a diagnosis of XP was made definitely. The patient was
      catheterized temporarily and treated with tamsulosin and estrogen. The patient
      underwent uneventful recovery after this conservative therapy. CONCLUSION:
      Histologic and immunohistochemical analyses are valuable in differentially
      diagnosing XP from high-grade prostate carcinoma. Treatment strategy of XP in
      principle is recommended to be the conservative method. Long-term follow-up earns
      are highly regarded considering the possibility of coexisting prostate cancer.

PMID- 27695692
TI  - Differential and Cooperative Cell Adhesion Regulates Cellular Pattern in Sensory
      Epithelia.
AB  - Animal tissues are composed of multiple cell types arranged in complex and
      elaborate patterns. In sensory epithelia, including the auditory epithelium and
      olfactory epithelium, different types of cells are arranged in unique mosaic
      patterns. These mosaic patterns are evolutionarily conserved, and are thought to
      be important for hearing and olfaction. Recent progress has provided accumulating
      evidence that the cellular pattern formation in epithelia involves cell
      rearrangements, movements, and shape changes. These morphogenetic processes are
      largely mediated by intercellular adhesion systems. Differential adhesion and
      cortical tension have been proposed to promote cell rearrangements. Many
      different types of cells in tissues express various types of cell adhesion
      molecules. Although cooperative mechanisms between multiple adhesive systems are
      likely to contribute to the production of complex cell patterns, our current
      understanding of the cooperative roles between multiple adhesion systems is
      insufficient to entirely explain the complex mechanisms underlying cellular
      patterning. Recent studies have revealed that nectins, in cooperation with
      cadherins, are crucial for the mosaic cellular patterning in sensory organs. The
      nectin and cadherin systems are interacted with one another, and these
      interactions provide cells with differential adhesive affinities for complex
      cellular pattern formations in sensory epithelia, which cannot be achieved by a
      single mechanism.

PMID- 27695693
TI  - The First 500 Registrations to the Research Registry(r): Advancing Registration
      of Under-Registered Study Types.
AB  - INTRODUCTION: The Declaration of Helsinki 2013 encourages the registration of all
      research studies involving human participants. However, emphasis has been placed
      on prospective clinical trials, and it is estimated that only 10% of
      observational studies are registered. In response, Research Registry(r) was
      launched in February 2015; a retrospectively curated registry that is free and
      easy to use. Research Registry(r) enables prospective or retrospective
      registration of studies, including those study types that cannot be registered on
      existing registries. In this study, we describe the first 500 registrations on
      Research Registry(r). METHODS: Since the launch of Research Registry(r) in
      February 2015, data of registrations have been collected, including type of
      studies registered, country of origin, and data curation activity. Inappropriate
      registrations, such as duplicates, were identified by the data curation process.
      These were removed from the database or modified as required. A quality score was
      assigned for each registration, based on Sir Austin Bradford Hill's criteria on
      what research studies should convey. Changes in quality scores over time were
      assessed. RESULTS: A total of 500 studies were registered on Research Registry(r)
      from February 2015 to October 2015, with a total of 1.7 million patients
      enrolled. The most common study types were retrospective cohort studies (37.2%),
      case series (14.8%), and first-in-man case reports (10.4%). Registrations were
      received from 57 different countries; the most submissions were received from
      Turkey, followed by China and the United Kingdom. Retrospective data curation
      identified 80 studies that were initially registered as the incorrect study type,
      and were subsequently correct. The Kruskal-Wallis test identified a significant
      improvement in quality scores for registrations from February 2015 to October
      2015 (p < 0.0001). CONCLUSIONS: Since its conception in February 2015, Research
      Registry(r) has established itself as a new registry that is free, easy to use,
      and enables the registration of various study types, including observational
      studies and first-in-man case reports. Going forward, our plan is to continue
      developing Research Registry(r) in line with user feedback and usability studies.
      We plan to further promote Research Registry(r) to advance the cause of
      registration of research, to increase compliance with the Declaration of Helsinki
      2013.

PMID- 27695694
TI  - Glycation in Demetalated Superoxide Dismutase 1 Prevents Amyloid Aggregation and
      Produces Cytotoxic Ages Adducts.
AB  - Superoxide dismutase 1 (SOD1) has been implicated with familial amyotrophic
      lateral sclerosis (fALS) through accumulation of protein amyloid aggregates in
      motor neurons of patients. Amyloid aggregates and protein inclusions are a common
      pathological feature of many neurological disorders in which protein aggregation
      seems to be directly related to neurotoxicity. Although, extensive studies
      performed on the aggregation process of several amyloidogenic proteins in vitro
      allowed the identification of many physiological factors involved, the molecular
      mechanisms underlying the formation of amyloid aggregates in vivo and in
      pathological conditions are still poorly understood. Post-translational
      modifications are known to affect protein structure and function and, recently,
      much attention has been devoted to the role played by non-enzymatic glycation in
      stimulating amyloid aggregation and cellular toxicity. In particular, glycation
      seems to have a determining role both in sporadic and familial forms of ALS and
      SOD1 has been shown to be glycated in vivo The aim of this study was to
      investigate the role of glycation on the amyloid aggregation process of both wild
      type SOD1 and its ALS-related mutant G93A. To this aim, the glycation kinetics of
      both native and demetalated SOD have been followed using two different glycating
      agents, i.e., D-ribose and methylglyoxal. The effect of glycation on the
      structure and the amyloid aggregation propensity of native and ApoSOD has been
      also investigated using a combination of biophysical and biochemical techniques.
      In addition, the effect of SOD glycated species on cellular toxicity and reactive
      oxygen species (ROS) production has been evaluated in different cellular models.
      The results provided by this study contribute to clarify the role of glycation in
      amyloid aggregation and suggest a direct implication of glycation in the
      pathology of fALS.

PMID- 27695695
TI  - A Comparison of Classical and H-Type Bovine Spongiform Encephalopathy Associated
      with E211K Prion Protein Polymorphism in Wild-Type and EK211 Cattle Following
      Intracranial Inoculation.
AB  - In 2006, a case of H-type bovine spongiform encephalopathy (BSE-H) was diagnosed
      in a cow that was associated with a heritable polymorphism in the bovine prion
      protein gene (PRNP) resulting in a lysine for glutamate amino acid substitution
      at codon 211 (called E211K) of the prion protein. Although the prevalence of this
      polymorphism is low, cattle carrying the K211 allele may be predisposed to rapid
      onset of BSE-H when exposed or to the potential development of a genetic BSE.
      This study was conducted to better understand the relationship between the K211
      polymorphism and its effect on BSE phenotype. BSE-H from the US 2006 case was
      inoculated intracranially (IC) in one PRNP wild-type (EE211) calf and one EK211
      calf. In addition, one wild-type calf and one EK211 calf were inoculated IC with
      brain homogenate from a US 2003 classical BSE case. All cattle developed clinical
      disease. The survival time of the E211K BSE-H inoculated EK211 calf (10 months)
      was shorter than the wild-type calf (18 months). This genotype effect was not
      observed in classical BSE inoculated cattle (both 26 months). Significant changes
      in retinal function were observed in H-type BSE challenged cattle only. Cattle
      challenged with the same inoculum showed similar severity and neuroanatomical
      distribution of vacuolation and disease-associated prion protein deposition in
      the brain, though differences in neuropathology were observed between E211K BSE-H
      and classical BSE inoculated animals. Western blot results for brain tissue from
      challenged animals were consistent with the inoculum strains. This study
      demonstrates that the phenotype of E211K BSE-H remains stable when transmitted to
      cattle without the K211 polymorphism, and exhibits a number of features that
      differ from classical BSE in both wild-type and heterozygous EK211 animals.

PMID- 27695696
TI  - Antimicrobial Susceptibility Patterns of Environmental Streptococci Recovered
      from Bovine Milk Samples in the Maritime Provinces of Canada.
AB  - Determination of antimicrobial susceptibility of bovine mastitis pathogens is
      important for guiding antimicrobial treatment decisions and for the detection of
      emerging resistance. Environmental streptococci are ubiquitous in the farm
      environment and are a frequent cause of mastitis in dairy cows. The aim of the
      study was to determine patterns of antimicrobial susceptibility among species of
      environmental streptococci isolated from dairy cows in the Maritime Provinces of
      Canada. The collection consisted of 192 isolates identified in milk samples
      collected from 177 cows originating from 18 dairy herds. Results were aggregated
      into: (1) Streptococcus uberis (n = 70), (2) Streptococcus dysgalactiae (n = 28),
      (3) other Streptococci spp. (n = 35), (4), Lactococcus spp. (n = 32), and (5)
      Enterococcus spp. (n = 27). Minimum inhibitory concentrations (MICs) were
      determined using the Sensititre microdilution system and mastitis plate format.
      Multilevel logistic regression models were used to analyze the data, with
      antimicrobial susceptibility as the outcome. The proportion of susceptible S.
      uberis ranged from 23% (for penicillin) to 99% (for penicillin/novobiocin), with
      a median of 82%. All S. dysgalactiae were susceptible to all antimicrobials
      except for penicillin (93% susceptible) and tetracycline (18% susceptible). The
      range of susceptibility for other Streptococcus spp. was 43% (for tetracycline)
      to 100%, with a median percent susceptibility of 92%. Lactococcus spp. isolates
      displayed percent susceptibilities ranging from 0% (for penicillin) to 97% (for
      erythromycin), median 75%. For the antimicrobials tested, the minimum inhibitory
      concentrations were higher for Enterococcus spp. than for the other species.
      According to the multilevel models, there was a significant interaction between
      antimicrobial and bacterial species, indicating that susceptibility against a
      particular antimicrobial varied among the species of environmental streptococci
      and vice versa. Generally, susceptibility decreased with increasing within-herd
      average somatic cell count, isolates recovered in mid-lactation were more
      susceptible than isolates recovered in early lactation, and isolates recovered in
      samples collected post-clinical mastitis were more susceptible than isolates
      recovered from non-clinical lactating quarters. The results of this research
      support continued susceptibility of environmental streptococci to beta-lactam
      antimicrobials. A departure from the expected susceptibility to beta-lactams was
      the apparent reduced susceptibility of S. uberis to penicillin.

PMID- 27695697
TI  - A Novel Model for Acute Peripheral Nerve Injury in the Horse and Evaluation of
      the Effect of Mesenchymal Stromal Cells Applied In Situ on Nerve Regeneration: A
      Preliminary Study.
AB  - Transplantation of mesenchymal stromal cells (MSCs) to sites of experimentally
      created nerve injury in laboratory animals has shown promising results in
      restoring nerve function. This approach for nerve regeneration has not been
      reported in horses. In this study, we first evaluated the in vitro ability of
      equine bone marrow-derived MSCs (EBM-MSCs) to trans-differentiate into Schwann
      like cells and subsequently tested the MSCs in vivo for their potential to
      regenerate a transected nerve after implantation. The EBM-MSCs from three equine
      donors were differentiated into SCLs for 7 days, in vitro, in the presence of
      specialized differentiation medium and evaluated for morphological
      characteristics, by using confocal microscopy, and for protein characteristics,
      by using selected Schwann cell markers (GFAP and S100b). The EBM-MSCs were then
      implanted into the fascia surrounding the ramus communicans of one fore limb of
      three healthy horses after a portion of this nerve was excised. The excised
      portion of the nerve was examined histologically at the time of transection, and
      stumps of the nerve were examined histologically at day 45 after transplantation.
      The EBM-MSCs from all donors demonstrated morphological and protein
      characteristics of those of Schwann cells 7 days after differentiation. Nerves
      implanted with EBM-MSCs after nerve transection did not show evidence of nerve
      regeneration at day 45. Examination of peripheral nerves collected 45 days after
      injury and stem cell treatment revealed no histological differences between
      nerves treated with MSCs and those treated with isotonic saline solution
      (controls). The optimal delivery of MSCs and the model suitable to study the
      efficacy of MSCs in nerve regeneration should be investigated.

PMID- 27695698
TI  - A Prospective, Randomized, Masked, and Placebo-Controlled Efficacy Study of
      Intraarticular Allogeneic Adipose Stem Cells for the Treatment of Osteoarthritis
      in Dogs.
AB  - Osteoarthritis (OA) is a degenerative joint disease with a high prevalence in
      dogs. Mesenchymal stem cells (MSCs) have been used to treat humans, dogs, and
      horses with OA. This report describes a prospective, randomized, blinded, and
      placebo-controlled clinical efficacy study of intraarticular allogeneic adipose
      stem cells for the treatment of dogs with OA. Health assessments and measurements
      of pain and activity impairment were performed at baseline and at selected time
      points through day 60. The primary outcome variable was the owner Client-Specific
      Outcome Measurement (CSOM) and secondary measures included veterinary pain on
      manipulation, veterinary global score, and owner global score. The dogs were
      treated with either a saline placebo or a single dose of allogeneic adipose
      derived MSCs in either one or two joints. Seventy-four dogs were statistically
      analyzed for efficacy outcomes. Success in the primary outcome variable, CSOM,
      was statistically improved in the treated dogs compared to the placebo dogs (79.2
      versus 55.4%, p = 0.029). The veterinary pain on manipulation score (92.8 versus
      50.2%, p = 0.017) and the veterinary global score (86.9 versus 30.8%, p = 0.009)
      were both statistically improved in treated dogs compared to placebo. There was
      no detected significant difference between treated and placebo dogs in the
      incidence of adverse events or negative health findings. Allogeneic adipose
      derived stem cell treatment was shown to be efficacious compared to placebo. This
      large study of dogs also provides valuable animal clinical safety and efficacy
      outcome data to our colleagues developing human stem cell therapy.

PMID- 27695699
TI  - Reduction of Salmonella Typhimurium by Fermentation Metabolites of Diamond V
      Original XPC in an In Vitro Anaerobic Mixed Chicken Cecal Culture.
AB  - Fermentation metabolites of Diamond V Original XPCTM (XPC), a biological product
      derived from yeast fermentation, were evaluated for their ability to reduce the
      Salmonella Typhimurium population using an in vitro mixed anaerobic culture
      system containing cecal microbiota to simulate chicken hindgut conditions. Four
      different samples were prepared: anaerobic mixed culture containing (1) feed
      only, (2) cecal only (ceca were harvested from 42 days old broiler chickens), (3)
      feed and cecal contents, and (4) feed, cecal contents, and 1% XPC. Two
      experimental conditions were investigated: Group 1, in which the cecal content
      was added at the same time as a S. Typhimurium marker strain and Group 2, in
      which the cecal content was preincubated for 24 h prior to the inoculation with
      the S. Typhimurium marker strain. The mixed cultures were incubated anaerobically
      at 37 degrees C, and the S. Typhimurium marker strain was enumerated at 0, 24,
      and 48 h. Analysis of short chain fatty acids was also conducted for 24 h. In the
      Group 1 experiment, adding XPC did not exhibit significant reduction of S.
      Typhimurium. However, the presence of XPC resulted in rapid reduction of S.
      Typhimurium in Group 2. S. Typhimurium was reduced from 6.81 log10 CFU/ml (0 h)
      to 3.73 log10 CFU/ml and 1.19 log10 CFU/ml after 24 and 48 h, respectively. These
      levels were also 2.47 log10 and 2.72 log10 lower than the S. Typhimurium level
      recovered from the control culture with feed and cecal contents, but without XPC.
      Based on these results, it appears that the ability of XPC to reduce S.
      Typhimurium requires the presence of the cecal microbiota. Short chain fatty acid
      analysis indicated that acetate and butyrate concentrations of cultures
      containing XPC were twofold greater than the control cultures by 24 h of
      anaerobic growth. Results from the present study suggest that dietary inclusion
      of XPC may influence cecal microbiota fermentation and has the potential to
      reduce Salmonella in the cecum. Implications of these findings suggest that XPC
      may decrease preharvest levels of Salmonella in broilers and layers.

PMID- 27695701
TI  - What Clinical Interventions Have Been Implemented to Prevent or Reduce Postpartum
      Hypertension Readmissions? A Clin-IQ.
AB  - A literature review was conducted to determine what clinical interventions have
      been studied and implemented to prevent and/or reduce postpartum hypertension
      readmissions. Appropriate verbal and printed educational materials should be
      given to the patient prior to discharge with use of the "teach back" method.
      Patients and health care providers within the multidisciplinary team should be
      educated on the warning signs and symptoms of worsening hypertensive disease and
      when to appropriately involve the obstetrician. The use of text messaging may be
      useful in preventing hospital readmissions by increasing patient follow-up and
      compliance and appropriately managing patients in the postpartum period. Treating
      postpartum patients with furosemide may decrease blood pressure and prevent
      postpartum hypertension and the need for antihypertensive therapy.

PMID- 27695702
TI  - Microfluidic-based Time-kill Kinetic Assay.
AB  - In many environments, bacteria favor a sessile, surface-attached community
      lifestyle. These communities, termed biofilms, are ubiquitous among many species
      of bacteria. In some cases, biofilms form under flow conditions. Flow chambers,
      and in particular microfluidic channels, can be used to observe biofilm
      development and physiological effects while varying nutrient conditions, flow
      velocities, or introducing antimicrobials to the biofilm in real time. Here, we
      describe a microfluidic-based kill-kinetics assay for the observation of
      antimicrobial effects on biofilms under flowing conditions.

PMID- 27695700
TI  - Regulatory Networks that Direct the Development of Specialized Cell Types in the
      Drosophila Heart.
AB  - The Drosophila cardiac tube was once thought to be a simple linear structure,
      however research over the past 15 years has revealed significant cellular and
      molecular complexity to this organ. Prior reviews have focused upon the gene
      regulatory networks responsible for the specification of the cardiac field and
      the activation of cardiac muscle structural genes. Here we focus upon
      highlighting the existence, function, and development of unique cell types within
      the dorsal vessel, and discuss their correspondence to analogous structures in
      the vertebrate heart.

PMID- 27695703
TI  - Gene Mutations Associated with Temporomandibular Joint Disorders: A Systematic
      Review.
AB  - BACKGROUND: The temporomandibular joint (TMJ) is a bilateral synovial joint
      between the mandible and the temporal bone of the skull. TMJ disorders (TMDs) are
      a set of complicated and poorly understood clinical conditions, in which TMDs are
      associated with a number of symptoms including pain and limited jaw movement. The
      increasing scientific evidence suggests that genetic factors play a significant
      role in the pathology of TMDs. However, the underlying mechanism of TMDs remains
      largely unknown. OBJECTIVE: The study aimed to determine the associated genes to
      TMDs in humans and animals. METHODS: The literature search was conducted through
      databases including Medline (Ovid), EMBASE (Ovid), and PubMed (NLM) by using
      scientific terms for TMDs and genetics in March 2015. Additional studies were
      identified by searching bibliographies of highly relevant articles and Scopus
      (Elsevier). RESULTS: Our systematic analyses identified 31 articles through
      literature searches. A total of 112 genes were identified to be significantly and
      specifically associated with TMDs. CONCLUSION: Our systematic review provides a
      list of accurate genes associated with TMDs and suggests a genetic contribution
      to the pathology of TMDs.

PMID- 27695704
TI  - Cognitive neuroscience of honesty and deception: A signaling framework.
AB  - Understanding the neural basis of human honesty and deception has enormous
      potential scientific and practical value. However, past approaches, largely
      developed out of studies with forensic applications in mind, are increasingly
      recognized as having serious methodological and conceptual shortcomings. Here we
      propose to address these challenges by drawing on so-called signaling games
      widely used in game theory and ethology to study behavioral and evolutionary
      consequences of information transmission and distortion. In particular, by
      separating and capturing distinct adaptive problems facing signal senders and
      receivers, signaling games provide a framework to organize the complex set of
      cognitive processes associated with honest and deceptive behavior. Furthermore,
      this framework provides novel insights into feasibility and practical challenges
      of neuroimaging-based lie detection.

PMID- 27695705
TI  - Predictive coding of multisensory timing.
AB  - The sense of time is foundational for perception and action, yet it frequently
      departs significantly from physical time. In the paper we review recent progress
      on temporal contextual effects, multisensory temporal integration, temporal
      recalibration, and related computational models. We suggest that subjective time
      arises from minimizing prediction errors and adaptive recalibration, which can be
      unified in the framework of predictive coding, a framework rooted in Helmholtz's
      'perception as inference'.

PMID- 27695706
TI  - Community violence concerns and adolescent sleep.
AB  - OBJECTIVE: The goal of this study was to examine links between concerns about
      community violence and objective and subjective sleep parameters in an adolescent
      sample. Sex was considered as a moderator of effects. DESIGN: The study used a
      cross-sectional design. PARTICIPANTS: The community-based sample included 252
      adolescents (53% girls) with an average age of 15.79 years (SD = 0.81) from the
      Southeastern United States. The sample included 34% African American and 66%
      European American adolescents from a wide range of socioeconomic backgrounds.
      MEASUREMENTS: Adolescent-reported community violence concerns were assessed using
      a composite of 3 separate subscales that measured perceived community safety and
      threats of community and school violence. Sleep duration and quality were
      assessed using actigraphy, and subjective sleep problems and daytime sleepiness
      were measured with subscales of the School Sleep Habits Survey. RESULTS:
      Community violence predicted lower sleep efficiency, more long-wake episodes, and
      more sleep/wake problems and sleepiness. Sex-related moderation effects revealed
      that girls in the sample were more vulnerable to the effects of violence concerns
      on their objective sleep quality. CONCLUSIONS: Findings highlight the role of
      community violence concerns on adolescents' sleep, revealing that greater
      community violence concerns are linked with lower levels of actigraphy-based and
      subjective reports of sleep quality, particularly for adolescent girls.
      Consideration of the mechanisms by which violence concerns may affect sleep is
      discussed.

PMID- 27695707
TI  - Using baseline cognitive severity for enriching Alzheimer's disease clinical
      trials: How does Mini-Mental State Examination predict rate of change?
AB  - BACKGROUND: Post hoc analyses from clinical trials in Alzheimer's disease suggest
      more cognitively impaired participants respond differently from less impaired on
      cognitive outcomes. We examined pooled clinical trials data to assess the utility
      of enriching trials using baseline cognition. METHODS: We included 2,882
      participants with mild to moderate AD in 7 studies from a meta-database. We used
      mixed effects models to estimate rate of decline in ADAS-cog scores among MMSE
      groups. FINDINGS: Baseline MMSE category was associated with baseline scores and
      rate of decline on the ADAS-cog, adjusting for age and education (both p<0.001).
      Greater baseline cognitive impairment was associated with more rapid progression.
      INTERPRETATIONS: Although we found significant differences in rate of decline,
      the majority of differences between individuals were from baseline ADAS-cog
      values. Enrichment based on MMSE would reduce the recruitment pool while adding
      only slightly to detecting differences in rate of progression and is not advised.

PMID- 27695708
TI  - Coordinated expression of tyro3, axl, and mer receptors in macrophage ontogeny.
AB  - The TAM receptors (Tyro3, Axl, and Mer) are a family of homologous receptor
      tyrosine kinases that inhibit Toll-like receptor signaling to regulate downstream
      pathways and restore homeostasis. TAM triple mutant mice (Tyro3-/-, Axl-/-, Mer-/
      ) have elevated levels of pro-inflammatory cytokines and are prone to developing
      lymphoproliferative disorders and autoimmunity. Understanding differential
      expression of TAM receptors among human subjects is critical to harnessing this
      pathway for therapeutic interventions. We have quantified changes in TAM
      expression during the ontogeny of human macrophages using paired samples of
      monocytes and macrophages to take advantage of characteristic expression within
      an individual. No significant differences in levels of Tyro3 were found between
      monocytes and macrophages (flow cytometry: p=0.652, immunoblot: p=0.231, qPCR:
      p=0.389). Protein levels of Axl were reduced (flow cytometry: p=0.049,
      immunoblot: p<0.001) when monocytes matured to macrophages. No significant
      differences in the levels of Axl mRNA transcripts were found (qPCR: p=0.082),
      however, Tyro3 and Axl were proportionate. The most striking difference was
      upregulation of expression of Mer with both protein and mRNA being significantly
      increased when monocytes developed into macrophages (flow cytometry: p<0.001,
      immunoblot: p<0.001, qPCR: p=0.004). A fuller characterization of TAM receptor
      expression in macrophage ontogeny informs our understanding of their function and
      potential therapeutic interventions.

PMID- 27695709
TI  - Demonstration of an Inline Publication Image Viewer: The Future of Radiological
      Publishing.
AB  - Publications which present images containing multi-dimensional image content have
      traditionally been confined to present information in a static 2-dimensional
      format. Inclusion of videos within a publication provides enhanced opportunities
      to present multi-dimensional image views rather than relying on static images to
      communicate findings. However, asignificant advance is presented in which an
      image viewer in integrated into Tomography's digital publication format allowing
      foruser manipulated and interactive multi-dimensional viewing of published image
      data directly inline with the manuscript. This 'small step' in technological
      advancement allowing for user manipulation and interrogation of multidimensional
      published image datais a 'giant leap' forward for publishing in the field of
      radiological sciences and beyond.

PMID- 27695710
TI  - A Structural Equation Model of HIV-related Symptoms, Depressive Symptoms, and
      Medication Adherence.
AB  - Adherence to combined antiretroviral therapy (cART) remains critical in
      management of HIV infection. This study evaluated depression as a potential
      mechanism by which HIV-related symptoms affect medication adherence and explored
      if particular clusters of HIV symptoms are susceptible to this mechanism.
      Baseline data from a multi-visit intervention study were analyzed among 124
      persons living with HIV (PLWH). A bifactor model showed two clusters of HIV
      related symptom distress: general HIV-related symptoms and gastrointestinal (GI)
      symptoms. Structural equation modeling showed that both general HIV-related
      symptoms and GI symptoms were related to higher levels of depressive symptoms,
      and higher levels of depressive symptoms were related to lower levels of
      medication adherence. Although general HIV-related symptoms and GI symptoms were
      not directly related to adherence, they were indirectly associated with adherence
      via depression. The findings highlight the importance of early recognition and
      evaluation of symptoms of depression, as well as the underlying physical symptoms
      that might cause depression, to improve medication adherence.

PMID- 27695711
TI  - Effect of National Schistosomiasis Control Programme on Taenia solium taeniosis
      and porcine cysticercosis in rural communities of Tanzania.
AB  - Taenia solium is found throughout sub-Saharan Africa and co-endemic with
      schistosomiasis in many regions. Taenia solium leads to taeniosis and
      neurocysticercosis - the leading cause of preventable epilepsy globally. This
      study aimed to assess the effects of the National Schistosomiasis Control
      Programme on prevalence of taeniosis and porcine cysticercosis over a four year
      period in Tanzania. School-based mass drug administration (MDA) of praziquantel
      was carried out based on schistosomiasis endemicity. Four human and five porcine
      cross-sectional surveys were carried out from 2012 to 2015 in Mbozi and Mbeya
      district in Tanzania. Three rounds of school-based MDA of praziquantel were
      delivered in Mbozi and two in Mbeya. The prevalence of taeniosis and porcine
      cysticercosis was estimated annually. Stool samples were collected from humans
      and prevalence of taeniosis estimated by copro-Ag-ELISA. Blood samples from pigs
      were collected to estimate cysticercosis prevalence by Ag-ELISA. "Track-and
      treat" of taeniosis cases was carried out after each survey. In total 12082 stool
      samples and 4579 porcine serum samples were collected. Significantly fewer
      children (<= 15) from Mbozi were infected throughout the study than children from
      Mbeya who showed a significant decrease in copro-Ag prevalence after the first
      treatment only. During the final survey in Mbozi the prevalence of taeniosis in
      adults (1.8%) was significantly lower (p = 0.031, OR 0.40, CI: 0.17-0.89),
      compared to baseline (4.1%). The prevalence of porcine cysticercosis (8%) had
      also dropped significantly (p = 0.002, OR 0.49, CI: 0.32-0.76) in this district
      compared to baseline (13%), whereas no significant difference was seen in Mbeya
      compared to baseline. The study suggests that three rounds of MDA targeting
      schistosomiasis in school-aged children combined with 'track-and-treat'
      contributed to a reduction in prevalence of T. solium in this population, and
      also had a spillover effect on adults in treated areas as well as reducing the
      prevalence of T. solium in the intermediate pig host population. Elimination of
      T. solium in this area would require a One Health approach.

PMID- 27695712
TI  - RNA Editing Dynamically Rewrites the Cancer Code.
AB  - Global analyses of cancer transcriptomes demonstrate that ADAR (adenosine
      deaminase, RNA-specific)-mediated RNA editing dynamically contributes to genetic
      alterations in cancer, and directly correlates with progression and prognosis.
      RNA editing is abundant and frequently elevated in cancer, and affects
      functionally and clinically relevant sites in both coding and non-coding regions
      of the transcriptome. Therefore, ADAR and differentially edited transcripts may
      be promising biomarkers or targets for therapy.

PMID- 27695713
TI  - Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST
      Segment Elevation Myocardial Infarction.
AB  - BACKGROUND: Poloxamer 188 (P188) is a nonionic triblock copolymer believed to
      prevent cellular injury after ischemia and reperfusion. OBJECTIVES: This study
      compared intracoronary infusion of P188 immediately after reperfusion with
      delayed infusion through a peripheral intravenous catheter in a porcine model of
      ST segment elevation myocardial infarction (STEMI). Cellular and mitochondrial
      injury were assessed. METHODS: STEMI was induced in 55 pigs using 45 minutes of
      endovascular coronary artery occlusion. Pigs were then randomized to four groups:
      control, immediate intracoronary (IC) P188, delayed peripheral P188, and
      polyethylene glycol (PEG) infusion. Heart tissue was collected after 4 hours of
      reperfusion. Assessment of mitochondrial function or infarct size was performed.
      RESULTS: Mitochondrial yield improved significantly with IC P188 treatment
      compared to control animals (0.25% vs. 0.13%) suggesting improved mitochondrial
      morphology and survival. Mitochondrial respiration and calcium retention were
      also significantly improved with immediate IC P188 compared to controls (complex
      I RCI: 7.4 vs. 3.7 and calcium retention (nmol): 1152 vs. 386). This benefit was
      only observed with activation of complex I of the mitochondrial respiratory chain
      suggesting a specific impact of ischemia and reperfusion on this complex. Infarct
      size and serum troponin I were significantly reduced by immediate IC P188
      infusion (infarct size: 13.9% vs. 41.1% and troponin I (MUg/L): 19.2 vs. 77.4
      MUg/L). Delayed P188 and PEG infusion did not provide a significant benefit.
      CONCLUSIONS: Intracoronary infusion of P188 immediately upon reperfusion
      significantly reduces cellular and mitochondrial injury after ischemia and
      reperfusion in this clinically relevant porcine model of STEMI. The timing and
      route of delivery were critical to achieve the benefit.

PMID- 27695714
TI  - Silorane-based Composite Resin Restorations Are Not Better than Conventional
      Composites - A Meta-Analysis of Clinical Studies.
AB  - PURPOSE: To perform a systematic review of the clinical performance of a low
      polymerization shrinkage, siloranebased composite (SBC) compared with a
      methacrylate-based composite (MBC) in posterior restorations. MATERIALS AND
      METHODS: Electronic databases were searched: PubMed, Scopus, Bireme, Science
      Direct, Web of Science, ClinicalTrials.gov and OpenGrey. The search strategy
      included MeSH terms, synonyms and keywords with no language or date restrictions.
      Reference lists of eligible studies were cross checked in an attempt to identify
      additional studies. Based on the PICOS strategy, only randomized clinical trials
      (RCTs) were included. The risk of bias in the included studies was assessed and
      classified through the Cochrane Collaboration common scheme for bias. Two meta
      analyses were performed using RevMan software, one with all 11 studies and
      another that included only studies with over 24 months of follow-up, for the main
      parameters analyzed. RESULTS: A total of 544 studies were identified. After
      removing duplicates and examinating titles and abstracts, 17 texts were selected
      and read in full. Six of them were excluded, so the final sample of this
      systematic review included 11 studies. Six of the 11 studies were classified as
      having a "low risk of bias" and five were "unclear". The heterogeneity (I2) in
      all parameters was not significant. The exclusion of studies with less than 24
      months of follow- up did not change the final result of the meta-analysis: both
      SBC and MBC have satisfactory and statistically similar clinical performances.
      CONCLUSION: Low polymerization shrinkage is not the principal factor that
      determines the superiority of a resin.

PMID- 27695716
TI  - Surface Characterization and Short-term Adhesion to Zirconia after Ultra-short
      Pulsed Laser Irradiation.
AB  - PURPOSE: To evaluate the suitability of an ultra-short pulsed laser (USPL) to
      treat zirconia ceramic surfaces and increase their adhesion to dual-curing resin
      cement. MATERIALS AND METHODS: Twenty 10 * 10 * 5 mm3 blocks were prepared from a
      zirconia ceramic (Y-TZP). The specimens were polished and randomly assigned to
      four groups (n = 5) which received the following surface treatments: sandblasting
      (SB) with Al2O3 particles and silica coating (SC) with SiO2 particles as positive
      controls; two groups received USPL irradiation, one with 10 scan repetitions
      (L10) and the other with 20 (L20). Laser irradiation was performed at 1030 nm,
      2.3 J/cm2, 6 ps pulse duration. The ceramic blocks were duplicated in composite
      resin and cemented with a dual-curing resin cement. Half of the blocks were then
      stored in water (37 degrees C) for 24 h and the other half for 1 month. At each
      time, 40 to 60 sticks per group were subjected to microtensile bond strength
      testing. Data were analyzed statistically using the Kruskal-Wallis test (alpha =
      0.05). RESULTS: Laser-treated zirconia presented statistically significantly
      higher roughness than did SB and SC. After 24 h, the highest bond strength means
      (MPa) were achieved by L10 (42.3 +/- 10.8) and L20 (37.9 +/- 14.4), and both of
      them were statistically significantly higher than SB (22.0 +/- 5.3) and SC (20.8
      +/- 7.1) (p < 0.05). After 1 month of storage, L10- and L20-treated zirconia
      still showed significantly higher bond strengths than did SB- and SC-treated
      zirconia (p < 0.05). CONCLUSION: USPL irradiation significantly increases bond
      strength of zirconia ceramic to dual-curing resin cement and might be an
      alternative for improving adhesion to this material.

PMID- 27695715
TI  - Which Factors Influence the Shear Bond Strength of Sealant Materials?
AB  - PURPOSE: This study investigated the influence of several methodological details
      on the shear bond strength (SBS) testing of pit and fissure sealants. The
      following variables were considered: type of enamel surfaces, prismatic vs
      aprismatic enamel, etching time, and aging and shearing procedures. MATERIALS AND
      METHODS: The surfaces of 180 healthy human third molars were divided into 4
      different sections (mesial, distal, buccal, and oral). After tooth separation,
      the specimens were randomly allocated to the following groups: 1) enamel
      preparation: prismatic vs aprismatic; 2) etching: 30 s vs 60 s; 3) aging: 1 day
      or 3 months vs 5000 thermocycles; 4) shearing: notched-edge method (ISO
      29022:2013) vs knife-edge method. After following each protocol, SBS was
      determined using a universal testing machine, followed by failure mode analysis.
      Data were analysed using Mann-Whitney U-tests and regression analyses. RESULTS:
      In the aprismatic enamel group, the longer etching time resulted in slightly, not
      statistically significantly higher SBS. When aging sealants on aprismatic enamel
      with different procedures, significantly lower SBS was found for 5000
      thermocycles. In the case of aprismatic enamel etched for 60 s and sheared with
      the notched-edge blade, there was no significant difference between the aging
      procedures. Failure mode analysis showed adhesive failures to be predominant.
      Simple linear regression revealed that all of the included factors significantly
      influenced SBS. In a multiple linear regression model, the variables "aprismatic
      enamel" and "distal surface" were associated with a higher SBS; "5000
      thermocycles" reduced SBS significantly. CONCLUSION: Enamel grinding, aging
      method, and type of enamel surface significantly influenced the SBS.

PMID- 27695717
TI  - An analysis of general practice encounters by socioeconomic disadvantage.

PMID- 27695718
TI  - Meeting the primary care needs ?of young people in residential care.
AB  - BACKGROUND: Young people in out-of-home care, especially those with a history of
      multiple placements, typically have numerous and complex health needs, and worse
      health outcomes than their peers who grow up within a family of origin. A
      significant proportion of this can be attributed to policy failures and poor
      interagency communication. OBJECTIVE: The objective of this article is to
      describe the factors that contribute to the health needs of young people in out
      of-home care and the tools available to support general practitioners (GPs) to
      provide care. DISCUSSION: GPs are crucial in the early detection of health
      problems and intervention for this vulnerable population. Marked social and
      relational problems make the high-priority task of creating a safe and trusting
      environment a challenge. GPs must also work within the statutory requirements of
      each state and territory, and navigate the complex out-of-home care system. Using
      recommended frameworks and maintaining effective communication and support will
      improve outcomes for these young people, their families and the community.

PMID- 27695719
TI  - Teenage mothers.
AB  - BACKGROUND: Australia's teenage birth rate has fallen to historic lows, but
      teenage motherhood still occurs and can be challenging for mother and baby.
      OBJECTIVE: The aim of this article is to review current evidence on the
      epidemiology and clinical care of teenage pregnancy and parenting, and provide
      recommendations around management of these young people in Australia. DISCUSSION:
      Teenage mothers may have experienced family, sexual, and partner violence, family
      disruption, and socioeconomic disadvantage. Outcomes on a range of peripartum
      measures are worse for teenage mothers and their babies. Longer term risks for
      the mother include depression and rapid repeat pregnancy; for the child,
      intergenerational teenage parenthood; and for both, socioeconomic disadvantage.
      Teenage motherhood occurs more often within communities where poverty, Aboriginal
      and Torres Strait Islander status and rural/remote location intersect. General
      practitioners play a critical role in identification of at-risk teens, preventing
      unintended teenage pregnancy, clinical care of pregnant teens, and promoting the
      health and wellbeing of teenage mothers and their children.

PMID- 27695720
TI  - A practical overview of the treatment ?of chronic hepatitis C virus infection.
AB  - BACKGROUND: Although hepatitis C virus (HCV) infection is associated with
      significant morbidity and mortality, OBJECTIVE: This article provides an overview
      for GPs on the principles involved in assessing and treating patients with
      chronic hepatitis C within a community setting. DISCUSSION: Treatment with DAA
      medications listed on the PBS should be considered for all patients with chronic
      HCV infection. These regimens are well tolerated, highly efficacious and have all
      oral administration. A thorough pre-treatment evaluation should be undertaken,
      and patients with cirrhosis, significant comorbidities or potential drug-drug
      interactions should be referred to a specialist. Successful eradication of HCV is
      characterised by undetectable HCV ribonucleic acid viral load on polymerase chain
      reaction testing 12 weeks after treatment completion, although antibodies to HCV
      may remain positive for the rest of the patient's life.

PMID- 27695721
TI  - Uterine fibroids: Investigation ?and current management trends.
AB  - BACKGROUND: Uterine leiomyomas, or fibroids, represent a large proportion of
      gynaecological presentations in both general and specialist gynaecology practice.
      The diagnosis is relatively simple with current imaging modalities. The
      management of fibroids, however, is not always straightforward and can present
      many challenges. OBJECTIVE: This article reviews current approaches to the
      management of uterine fibroids, including novel techniques, and highlights
      important patient counselling points. DISCUSSION: Many fibroids cause
      debilitating symptoms that greatly affect a woman's quality of life. Traditional
      surgical treatment options include myomectomy and hysterectomy. Minimally
      invasive surgical and radiological techniques, as well as symptomatic treatment,
      including the use of hormonal medication, intrauterine devices, and endometrial
      ablation, have become increasingly popular treatment choices. While these
      treatments are associated with reduced perioperative morbidity and shorter
      hospital stays, patients should be carefully counselled regarding the risks and
      the benefits. General practitioners may often help to initiate discussions to
      assist women considering their management options.

PMID- 27695722
TI  - Seasonal influenza vaccination ?in Aboriginal children in Western ?Australia in
      2015.

PMID- 27695723
TI  - 'If they're your doctor, they should care about you': Women on release from
      prison and general practitioners.
AB  - BACKGROUND: Nearly half of the people leaving prison see a general practitioner
      (GP) within a month of release, which provides an opportunity to promote health
      for this vulnerable group. OBJECTIVE: The objective of this article is to examine
      the expectations and experiences of GP care of women leaving prison. METHODS:
      Semi-structured interviews pre-release and post-release from prison were analysed
      using inductive thematic analysis. RESULTS: Sixty-nine interviews were conducted
      with 40 women while they were still in prison and 29 of these women after they
      were released. Women perceived GPs as lacking interest in their social support
      needs and believed GPs needed more skills in substance misuse management. Given
      the fear of stigma, women may not disclose recent incarceration, affecting the
      continuity of healthcare initiated in prison. DISCUSSION: GPs' acknowledgement
      of, and assistance with, the broad issues that have an impact on the health and
      wellbeing of women after release is valued. Whole-person care also requires GP
      accessibility, management of substance misuse, continuity of care and
      understanding of the stigma associated with incarceration.

PMID- 27695724
TI  - Australian women's experiences of the subdermal contraceptive implant: A
      qualitative perspective.
AB  - BACKGROUND: The number of prescriptions for contraceptive implants has steadily
      increased in Australia, but implant use is still low. OBJECTIVE: The objectives
      of the study were to describe women's nuanced responses, and characterise their
      multidimensional and complex reasons for (dis)continuing use of the contraceptive
      implant. METHODS: A descriptive qualitative approach was used for this study. A
      larger qualitative study using in-depth, open-ended interviews, conducted in New
      South Wales between 2012 and 2013 with 94 women aged 16-49 years who had used
      contraception, included 10 interviews containing accounts of implant use. The 10
      interviews were analysed thematically in the present study. RESULTS: The three
      main themes analysed from the 10 interviews were perceived benefits, undesirable
      experiences and perseverance. DISCUSSION: The participants were well informed
      about the benefits of the implant. Many persevered with it for a significant
      period of time before discontinuing it, despite experiencing side effects such as
      bleeding or mood changes. A decision to discontinue was often only made after an
      accumulation of multiple side effects.

PMID- 27695725
TI  - Patients' perspectives about why they have their contraceptive Implanon NXT
      device removed early.
AB  - BACKGROUND: Women with long-acting, reversible contraceptive devices inserted may
      choose to remove them prior to their planned expiry dates. OBJECTIVE: The
      objective of this study was to explore Australian women's experiences with the
      etonogestrel subdermal contraceptive implant (Implanon NXT) and why they had it
      removed early. METHODS: Semi-structured interviews were conducted with 18 women
      between June 2013 and January 2014. Transcriptions of the audio-taped interviews
      were analysed using a constant comparative analysis framework. RESULTS: Two core
      themes of participants' responses that were identified in this study were
      influences on choice of contraception, which included convenience and information
      sources; and influences on removal of contraception, which included side effects
      and their negative impacts on relationships and financial costs. DISCUSSION: This
      study highlights that women's experiences with side effects contribute to the
      early removal of long-acting contraceptive devices such as Implanon NXT. This
      study emphasises the importance of general practitioners (GPs) in providing
      comprehensive information about the benefits and potential side effects
      associated with using these implants.

PMID- 27695726
TI  - General practitioner perspectives on referrals to paediatric public specialty
      clinics.
AB  - BACKGROUND: Changes in the demography of Australia have resulted in changes in
      patterns of primary care delivery. One of these changes is that the proportion of
      paediatric visits has decreased. OBJECTIVE: The objectives of the article are to
      examine patient, practice and personal factors that influence a general
      practitioner's (GP's) decision to refer patients for paediatric specialty care,
      and investigate referral goals and experience with shared care. METHODS: A mail
      survey was sent out to 400 GPs who had referred at least two children to public
      hospital specialty clinics during 2014. RESULTS: The response rate for the mail
      survey was 67%. The factors most commonly reported by GPs as 'Somewhat important'
      or 'Very important' in the decision to refer were whether they had enough
      knowledge of a specific condition (81%) or did not have experience with similar
      patients (75%). About one-quarter (26%) of GPs reported that a parental request
      'Frequently' or 'Almost always' influenced their referral decision. A similar pro
      portion (26%) placed importance on whether they had sufficient time for a
      specific patient. DISCUSSION: Understanding the perspectives and determinants of
      GP referrals for paediatric specialty care is important, especially in the
      context of changing patterns of primary care delivery.

PMID- 27695727
TI  - Urban general practice and medical education: Academic outcomes from a unique
      urban, longitudinal integrated community-based program.
AB  - BACKGROUND: In 2009, Flinders University established an urban, community-based,
      longitudinal integrated program providing medical students extended placements
      that offered continuities of patient care, clinical supervision and peer group.
      OBJECTIVE: The aim of this research was to analyse academic outcomes of the new
      placement program. METHODS: The results of all students undertaking Year 3 exams
      from 2011 to 2014 were collected and analysed. The Years 1 and 2 exam results for
      students in the new program were also analysed. RESULTS: Students in the new
      placement program achieved significantly higher grades than those who undertook
      the traditional rotations program, with aver-age scores of 69.05, compared with
      66.45 (P = 0.03). Analysis of average class ranking for students who undertook
      the new program showed a statistically significant improvement from 59th in class
      to 48th in class (P = 0.03). DISCUSSION: This evaluation shows that an urban,
      community-based, longitudinal integrated clerkship centred in general practice
      provides at least academically equivalent outcomes to traditional rotations-based
      programs.

PMID- 27695728
TI  - The medical home: A need for collaborative practice.

PMID- 27695730
TI  - Alcohol screening and brief interventions in primary care - Evidence and a
      pragmatic practice-based approach.
AB  - BACKGROUND: Risky alcohol drinking is a common problem in adults presenting in
      Australian general practice. Preventive health guidelines recommend routine
      delivery of alcohol screening and brief intervention (ASBI) by general
      practitioners (GPs). However, ASBIs have rarely been implemented successfully in
      a sustainable manner. OBJECTIVE: In this article, we explain the current state of
      empirical evidence for the effectiveness of ASBI in primary care and describe a
      pragmatic interpretation of how this evidence applies to routine care.
      DISCUSSION: The empirical evidence surrounding ASBIs is complex. ASBIs are
      efficacious in research settings, but their effectiveness when compared with
      control interventions in real-world practice is less certain. Alcohol assessment
      within therapeutic doctor-patient relationships, rather than the specific formal
      tools, may be the 'active ingredient'. A pragmatic, practice-based approach to
      early detection of risky drinking is to focus on strategies that allow asking
      patients about their drinking more regularly, documenting it, and using quality
      improvement methodology to improve alcohol recording data completeness for the
      practice population.

PMID- 27695729
TI  - The evolving role of cardiac magnetic resonance imaging in the assessment of
      cardiovascular disease.
AB  - BACKGROUND: Imaging of the heart is important in the diagnosis and follow-up of a
      broad range of cardiac pathology. The authors discuss the growing role of cardiac
      magnetic resonance imaging (CMR) in cardiology practice and its relevance to
      primary healthcare. OBJECTIVE: In this article we discuss the advantages of CMR
      over other imaging modalities, and give a brief description of the common CMR
      techniques and cardiac pathologies where CMR is especially useful. DISCUSSION:
      CMR provides specific advantages over other cardiac imaging modalities when
      evaluating pathology in congenital heart disease, cardiac masses,
      cardiomyopathies, and in some aspects of ischaemic and valvular heart diseases.
      The strength of CMR in these pathologies includes its precise ana-tomical
      delineation of structures, characterisation of myocardial tissue, and accurate,
      reproducible measurements of blood volume and flow. CMR is used in inpatient and
      outpatient settings, and is available primarily in major hospitals.

PMID- 27695735
TI  - An Integrated Landscape Designed for Commodity and Bioenergy Crops for a Tile
      Drained Agricultural Watershed.
AB  - Locating bioenergy crops on strategically selected subfield areas of marginal
      interest for commodity agriculture can increase environmental sustainability.
      Location and choice of bioenergy crops should improve environmental benefits with
      minimal disruption of current food production systems. We identified subfield
      soils of a tile-drained agricultural watershed as marginal if they had areas of
      low crop productivity index (CPI), were susceptible to nitrate-nitrogen (NO-N)
      leaching, or were susceptible to at least two other forms of environmental
      degradation (marginal areas). In the test watershed (Indian Creek watershed, IL)
      with annual precipitation of 852 mm, 3% of soils were CPI areas and 22% were
      marginal areas. The Soil and Water Assessment Tool was used to forecast the
      impact of growing switchgrass ( L.), willow ( spp.), and big bluestem ( Vitman)
      in these subfield areas on annual grain yields, NO-N and sediment exports, and
      water yield. Simulated conversion of CPI areas from current land use to bioenergy
      crops had no significant ( 0.05) impact on grain production and reduced NO-N and
      sediment exports by 5.0 to 6.0% and 3.0%, respectively. Conversion of marginal
      areas from current land use to switchgrass forecasted the production of 34,000 t
      of biomass and reductions in NO-N (26.0%) and sediment (33.0%) exports.
      Alternatively, conversion of marginal areas from current land use to willow
      forecasted similar reductions as switchgrass for sediment but significantly (
      0.01) lower reductions in annual NO-N export (18.0 vs. 26.0%).

PMID- 27695736
TI  - Greenhouse Gas and Ammonia Emissions from Slurry Storage: Impacts of Temperature
      and Potential Mitigation through Covering (Pig Slurry) or Acidification (Cattle
      Slurry).
AB  - Storage of livestock slurries is a significant source of methane (CH) and ammonia
      (NH) emissions to the atmosphere, for which accurate quantification and potential
      mitigation methods are required. Methane and NH emissions were measured from
      pilot-scale cattle slurry (CS) and pig slurry (PS) stores under cool, temperate,
      and warm conditions (approximately 8, 11, and 17 degrees C, respectively) and
      including two potential mitigation practices: (i) a clay granule floating cover
      (PS) and (ii) slurry acidification (CS). Cumulative emissions of both gases were
      influenced by mean temperature over the storage period. Methane emissions from
      the control treatments over the 2-mo storage periods for the cool, temperate, and
      warm periods were 0.3, 0.1, and 34.3 g CH kg slurry volatile solids for CS and
      4.4, 20.1, and 27.7 g CH kg slurry volatile solids for PS. Respective NH
      emissions for each period were 4, 7, and 12% of initial slurry N content for CS
      and 12, 18, and 28% of initial slurry N content for PS. Covering PS with clay
      granules reduced NH emissions by 77% across the three storage periods but had no
      impact on CH emissions. Acidification of CS reduced CH and NH emissions by 61 and
      75%, respectively, across the three storage periods. Nitrous oxide emissions were
      also monitored but were insignificant. The development of approaches that take
      into account the influence of storage timing (temperature) and duration on
      emission estimates for national emission inventory purposes is recommended.

PMID- 27695737
TI  - Soil Aggregate Dynamics and Plant Community Response after Biosolids Application
      in a Semiarid Grassland.
AB  - Biosolids may improve the ecological function of degraded semiarid grasslands,
      but an understanding of the plant community is essential. An experiment was
      established in 2001 to determine the effects of a single surface application of
      biosolids on soil aggregate stability and the composition of the plant community
      in a semiarid grassland in British Columbia, Canada. Four treatments were
      evaluated: (i) surface biosolids application at 20 (Bio-20) and (ii) 60 Mg ha
      (Bio-60), (iii) mineral fertilizer, and (iv) a control. All treatments were
      replicated in four blocks. Soil was sampled during the spring (May), summer (June
      July), and fall (October) in 2005, 2006, and 2009; the plant community was
      assessed in 2009. The greatest increases in size of stable aggregates relative to
      the control were in the spring and summer, which coincided with a 1.6- to 2.1
      fold increase in the spring concentration of N within stable aggregates when
      biosolids were applied at 20 and 60 Mg ha , respectively. Nitrogen concentrations
      from the Bio-60 treatment were not different from the control, but the Bio-20
      treatment had 42% greater N than all other treatments during summer. Biosolids
      application in this ecosystem did not increase perennial forage grass species
      relative to the control, and when biosolids were applied at a rate of 60 Mg ha
      there was a 75% reduction in the perennial forage plant species. The application
      of biosolids to native grasslands in semiarid environments should be done
      cautiously, especially when winter annual plant species (e.g., cheatgrass [ L.])
      are present before application.

PMID- 27695738
TI  - Comparison of Nutrient and Metal Loadings with the Application of Swine Manure
      Slurries and Their Liquid Separates to Soils.
AB  - The accumulation of phosphorus (P) and metals is a serious concern with the
      continuous application of manure to agricultural soils. Solid-liquid separation
      of swine slurry is a promising approach to reduce P and metal loadings through
      application of separated liquid (SL) as a nutrient source. However, little
      information is available on nutrient and metal loadings with the application of
      SL compared with unseparated raw manure (RM). We analyzed element concentrations
      and calculated nutrient and metal loadings for RM and their respective SL
      applications, considering an application rate of 100 kg total nitrogen (N) ha.
      Samples of SL were obtained through three separation techniques: (i)
      centrifugation without a flocculant, (ii) centrifugation with a flocculant, and
      (iii) rotary press with a flocculant. Irrespective of separation technique,
      calculated P loadings with the application of SL were only 50 to 70% of that of
      RM at equivalent rates of total N yet exceeded crop removal rate. In contrast,
      calculated K and Na loadings with SL application were significantly greater than
      with RM, indicating a possible build-up of K and Na in soil. Calculated Ca and Mg
      loadings were significantly greater with RM than with SL. Loadings of Al, As, Ba,
      Cd, Cr, Fe, Mn, Ni, Pb, Sn, Se, Ti, and V were low, whereas Cu and Zn loadings
      were above crop removal rates for RM and SL. For solid-liquid separation to
      provide a lasting solution to the problem of P and metal accumulation, the SL
      must be supplemented with commercial N fertilizer to meet crop N demand.

PMID- 27695740
TI  - Nitrogen Management for Corn and Groundwater Quality in Upper Midwest Irrigated
      Sands.
AB  - Groundwater contamination from NO-N leaching in corn ( L.) production with coarse
      textured soils poses an environmental concern. Our objectives were to evaluate NO
      N leaching in continuous corn (CC), corn after soybean ( L.) (CSb), and soybean
      after corn (SbC) in irrigated sandy soils in Minnesota related to (i) N rate
      using best management practices of split-N application, (ii) a split-N
      application and single preplant applications of enhanced-efficiency fertilizers
      (EEF), and (iii) residual N treatment in SbC. Urea (0-315 kg N ha in 45-kg
      increments) was broadcast as a split application (half at preplant and half at
      the V4 development stage) and polymer-coated urea (ESN), ESN/urea, and SuperU at
      preplant at a rate of 180 kg N ha on an Arvilla sandy loam soil. In May and June,
      75% of the total drainage and 73% of the total NO-N leached occurred. At the
      economic optimum N rate (EONR), season-long NO-N leaching rates were 86 and 106
      kg NO-N ha for CC and CSb, respectively. In CC, reducing the EONR by 20% reduced
      grain yield by 4% and NO-N leached by 9%, and a 25% reduction in EONR resulted in
      an additional 2% reduction for both, whereas no significant reductions occurred
      for CSb. Similar NO-N leaching occurred with EEFs and the split-N application.
      After 4 yr of no N application, we measured 9 to 20 mg NO-N L and leaching of 21
      to 51 kg NO-N ha, highlighting the difficulty of meeting drinking water quality
      standards in corn cropping systems.

PMID- 27695739
TI  - Enabling Science Support for Better Decision-Making when Responding to Chemical
      Spills.
AB  - Chemical spills and accidents contaminate the environment and disrupt societies
      and economies around the globe. In the United States there were approximately
      172,000 chemical spills that affected US waterbodies from 2004 to 2014. More than
      8000 of these spills involved non-petroleum-related chemicals. Traditional
      emergency responses or incident command structures (ICSs) that respond to
      chemical spills require coordinated efforts by predominantly government personnel
      from multiple disciplines, including disaster management, public health, and
      environmental protection. However, the requirements of emergency response teams
      for science support might not be met within the traditional ICS. We describe the
      US ICS as an example of emergency-response approaches to chemical spills and
      provide examples in which external scientific support from research personnel
      benefitted the ICS emergency response, focusing primarily on nonpetroleum
      chemical spills. We then propose immediate, near-term, and long-term activities
      to support the response to chemical spills, focusing on nonpetroleum chemical
      spills. Further, we call for science support for spill prevention and near-term
      spill-incident response and identify longer-term research needs. The development
      of a formal mechanism for external science support of ICS from governmental and
      nongovernmental scientists would benefit rapid responders, advance incident- and
      crisis-response science, and aid society in coping with and recovering from
      chemical spills.

PMID- 27695741
TI  - Confirmation of the Impact of Onsite Wastewater Treatment Systems on Stream Base
      Flow Nitrogen Concentrations in Urban Watersheds of Metropolitan Atlanta, GA.
AB  - Wastewater and lawn fertilizer potentially contribute to degraded water quality
      in urban watersheds. Previously we described a study from 2011 to 2012 in which
      we examined the effect of the density of onsite wastewater treatment systems
      (OWTS) on nitrogen concentrations in 24 small streams in metropolitan Atlanta.
      Our objective in this study was to confirm that the impact on water quality that
      we observed was due to OWTS and not lawn fertilizer. We sampled the same 24
      streams again in 2013 and 2014, representing watersheds ranging in area from 0.18
      to 8.8 km. We conducted regression analysis of the effect of OWTS and season,
      used dual-isotope analysis (nitrogen and oxygen in nitrate) to identify sources
      and determine the effect of denitrification and mixing, and conducted stream
      walks to identify areas where animals had access to the streams. Twelve streams
      were characterized as high-density (HD, more than 75 systems km) OWTS and 12 as
      low-density (LD, less than 75 systems km) OWTS. Water samples were collected
      three times a year under base-flow conditions, from November 2011 to July 2014,
      and analyzed for nitrate (NO-N), ammonium (NH-N), and total Kjeldahl nitrogen.
      Total nitrogen and NO-N concentrations increased linearly with increasing OWTS
      density above a threshold of about 75 OWTS km. Dual-isotope analysis of NO showed
      that stream NO originated predominantly from OWTS in HD watersheds and from a
      combination of animal waste and perhaps organic N in LD watersheds. Stream walks
      showed that livestock had access to some of the LD streams with high N
      concentrations. Our results confirm that HD OWTS can significantly degrade water
      quality at the watershed scale.

PMID- 27695743
TI  - Copper and Zinc Runoff from Land Application of Composted Poultry Litter.
AB  - Regions with long-term animal manure applications based on nitrogen (N)
      requirements have concerns regarding elevated nutrient levels. Most attention has
      focused on phosphorus (P), but heavy metal accumulation has received attention
      due to perceived environmental concerns. Composting is a potential management
      practice that can reduce total manure mass and volume while creating a stabilized
      product that has less odor and fewer pathogens. However, composting animal
      manures can lead to high N loss via ammonia volatilization and increased
      concentrations of nonvolatile nutrients. The objective of this study was to
      measure copper (Cu) and zinc (Zn) concentrations in runoff water from plots
      fertilized with composted and fresh poultry litter. Seven treatments were
      evaluated in the first year: (i) unfertilized control, (ii) fresh poultry litter,
      (iii) normal compost (no amendment), (iv) composted litter with alum, (v)
      composted litter with phosphoric acid, (vi) composted litter with a microbial
      mixture, and (vii) composted litter with alum + microbial mixture. Six of these
      treatments were evaluated in Year 2 (alum + microbial mixture was not evaluated
      in Year 2). Rainfall simulators were used to produce a 5 cm h storm event
      sufficient in length to cause 30 min of continuous runoff. Concentrations of Cu
      and Zn were elevated in compost compared with fresh poultry litter. However,
      metal concentrations in compost did not correlate well with metal concentrations
      in runoff water and may have been affected by compost maturity and amendment.
      Total Cu and Zn concentrations in runoff water did not differ between alum
      amended compost and fresh poultry litter in each year.

PMID- 27695742
TI  - An Evaluation of the Contribution of Macro- and Microelements from Colonial
      Nesting Waterbirds to Surface Water.
AB  - Macro- and microelements contained in the feces of cattle egrets () and other
      colonial birds in heronries can be sources of contamination of nearby waterways.
      Concentrations of the macroelements potassium (K), calcium (Ca), magnesium (Mg),
      sodium (Na), sulfur (S) and the microelements zinc (Zn), copper (Cu), iron (Fe),
      manganese (Mn), and boron (B) were measured in water and fecal samples collected
      from four locations containing heronries during the breeding seasons of 2011,
      2012, and 2013. Nitrogen and phosphorus were measured but not reported in this
      study. Concentrations of K in feces ranged from 8.19 * 10 +/- 4.38 * 10 to 4.88 *
      10 +/- 7.57 * 10 mg kg, and concentrations in water ranged from 3.92 +/- 0.05 to
      17.93 +/- 0.37 mg L. Similarly, concentrations of Ca in feces ranged from 4.17 *
      10 +/- 1.84 * 10 to 1.16 * 10 +/- 4.14 * 10 mg L, and concentrations in water
      ranged from 25.28 +/- 0.89 to 67.88 +/- 2.02 mg L. When birds nested directly
      over water, concentrations of K, Ca, and Mg in water were significantly higher (
      < 0.05) than concentrations in water adjacent to birds nesting on islands. The
      results from this study show that macroelements from avian feces have the
      potential to enrich surface water and to negatively affect surface water quality.
      These results provide information regarding the contribution of nutrients from
      heronries (comprised primarily by cattle egrets) to watersheds.

PMID- 27695744
TI  - Transport of Glyphosate and Aminomethylphosphonic Acid under Two Soil Management
      Practices in an Italian Vineyard.
AB  - Worldwide, glyphosate is the most widely used herbicide in controlling the growth
      of annual and perennial weeds. An increasing number of studies have highlighted
      the environmental risk resulting from the use of this molecule in aquatic and
      terrestrial ecosystems. The objective of the study was to determine the transport
      of glyphosate and its degradation product, aminomethylphosphonic acid (AMPA),
      through runoff and transported sediment from a vineyard under two different soil
      management systems: harrowed inter-row (HR) and permanent grass covered inter-row
      (GR). The study was performed over a period of 4 yr. Glyphosate and AMPA
      concentrations were found to be higher in runoff and in transported sediment from
      HR compared with GR, regardless of the amount of runoff and transported sediment.
      The mean annual percentages of glyphosate loss, via runoff and transported
      sediment, were about 1.37 and 0.73% for HR and GR, respectively.
      Aminomethylphosphonic acid represented approximately 30.9 and 40.0% of the total
      glyphosate losses in GR and HR, respectively. Moreover, results suggested that
      rains occurring within 4 wk after treatment could cause the transport of
      glyphosate and AMPA in high concentrations. Soil analyses indicated that
      glyphosate content was below detection within 1 yr, whereas AMPA remained in the
      soil profiles along the vine row and in the inter-row. Results indicated that GR
      can reduce soil and herbicide loss by runoff in vineyard cropping system.

PMID- 27695745
TI  - Residual Effects of Fertilization History Increase Nitrous Oxide Emissions from
      Zero-N Controls: Implications for Estimating Fertilizer-Induced Emission Factors.
AB  - Agricultural N fertilization is the dominant driver of increasing atmospheric
      nitrous oxide (NO) concentrations over the past half-century, yet there is
      considerable uncertainty in estimates of NO emissions from agriculture. Such
      estimates are typically based on the amount of N applied and a fertilizer-induced
      emission factor (EF), which is calculated as the difference in emissions between
      a fertilized plot and a zero-N control plot divided by the amount of N applied. A
      fertilizer-induced EF of 1% is currently recognized by the Intergovernmental
      Panel on Climate Change (IPCC) based on several studies analyzing published field
      measurements of NO emissions. Although many zero-N control plots used in these
      measurements received historical N applications, the potential for a residual
      impact of these inputs on NO emissions has been largely ignored and remains
      poorly understood. To address this issue, we compared NO emissions under
      laboratory conditions from soils sampled within zero-N control plots that had
      historically received N inputs versus soils from plots that had no N inputs for
      20 yr. Historical N fertilization of zero-N control plots increased initial NO
      emissions by roughly one order of magnitude on average relative to historically
      unfertilized control plots. Higher NO emissions were positively correlated with
      extractable N and potentially mineralizable N. This finding suggests that
      accounting for fertilization history may help reduce the uncertainty associated
      with the IPCC fertilizer-induced EF and more accurately estimate the contribution
      of fertilizer N to agricultural NO emissions, although further research to
      demonstrate this relationship in the field is needed.

PMID- 27695746
TI  - Dissipation of Antimicrobials in a Seasonally Frozen Soil after Beef Cattle
      Manure Application.
AB  - Land application of manure containing antimicrobials results in the dispersion of
      the antimicrobials in agro-ecosystems. Dissipation of excreted antimicrobials in
      seasonally frozen agricultural soils has not been fully characterized under field
      conditions. This study investigated the field dissipation kinetics of
      chlortetracycline, sulfamethazine, and tylosin over a 10-mo period after fall
      application of manure from cattle () administered 44 mg chlortetracycline
      (chlortetracycline treatment [CTC]), 44 mg each of chlortetracycline and
      sulfamethazine (CTCSMZ), or 11 mg tylosin per kg feed daily. Antimicrobial
      concentrations in manured soil reflected the same relative concentrations in
      manure: chlortetracycline > sulfamethazine > tylosin. The first-order dissipation
      half-life (DT) for chlortetracycline from the CTCSMZ treatment was 77 d during
      the growing season and 648 d during the nongrowing season when the soil was
      frozen for an extended period. By comparison, dissipation of chlortetracycline
      added alone (treatment CTC) did not differ significantly between the two seasons
      (mean DT, 121 d). During the nongrowing season, chlortetracycline from CTC
      dissipated faster ( = 0.004) than that from the CTCSMZ treatment, indicating that
      the presence of sulfamethazine may have altered the dissipation of
      chlortetracycline. Dissipation kinetics for sulfamethazine and tylosin were not
      determined due to low detection in the manure-amended soil. Sulfamethazine was
      detected (up to 16 +/- 10 ug kg) throughout the 10-mo monitoring period. Tylosin
      concentration was <=11 +/- 6.6 ug kg and gradually dissipated. Chlortetracycline
      was detectable 10 mo after application in the seasonally frozen soil, indicating
      a risk for residue build-up in the soil and subsequent offsite contamination.

PMID- 27695747
TI  - Simulated Effects of Soil Texture on Nitrous Oxide Emission Factors from Corn and
      Soybean Agroecosystems in Wisconsin.
AB  - Soil texture is known to have an influence on the physical and biological
      processes that produce NO emissions in agricultural fields, yet comparisons
      across soil textural types are limited by considerations of time and
      practicality. We used the DayCent biogeochemical model to assess the effects of
      soil texture on NO emissions from agriculturally productive soils from four
      counties in Wisconsin. We validated the DayCent model using field data from 2 yr
      of a long-term (approximately 20-yr) cropping systems trial and then simulated
      yield and NO emissions from continuous corn ( L.) and corn-soybean ( L.) cropping
      systems across 35 Wisconsin soil series classified as either silt loam, sandy
      loam, or loamy sand. Silt loam soils had the highest NO emissions of all soil
      types, exhibiting 80 to 158% greater mean emissions and 100 to 282% greater
      emission factors compared with loamy sand and sandy loam soils, respectively. The
      model predicts that for these soils under these cropping systems, denitrification
      constituted the majority of the NO flux only in the silt loam soils. However,
      across all soil textures, locations, and years, denitrification explained the
      most variation (74-98%) in total NO emissions. Our results suggest that soil
      texture is an important factor in determining a range of NO emission
      characteristics and is critical for estimating future NO emissions from
      agricultural fields.

PMID- 27695748
TI  - Subsurface Transport of in Soils of Wisconsin's Carbonate Aquifer Region.
AB  - is a waterborne pathogen known to have a significant reservoir in bovine manure.
      Land-dependent manure disposal may not result in significant or reliable pathogen
      attenuation and, therefore, presents a risk for transport of pathogenic spp. to
      groundwater. One factor missing in the existing literature is the role soil
      characteristics play in affecting oocyst transport. Of specific concern in
      regions with carbonate geology are macropores and other soil structures that
      contribute to preferential flow. Therefore, research is needed to understand soil
      type effects and important transport pathways for pathogens such as oocysts to
      drinking water wells. This study investigated transport potential in several
      soils overlying Wisconsin's vulnerable carbonate aquifer and related the soil
      transport to soil series and textural class. Experimental work involved
      monitoring the transport of oocysts through intact soil columns of different soil
      series under simulated rain conditions. Results demonstrate that a significant
      portion of oocysts will sorb or be physically entrapped in the soil, especially
      in soil with high clay content. However, silt loam soils with comparatively lower
      clay content demonstrated an ability to transport oocysts through the soil
      profile primarily via the first flush of water infiltrating through soil
      macropores. The rate of oocyst migration in silt loam soils paralleled the
      bromide tracer front, thus bypassing the soils' ability to strain or adsorb
      oocysts out of infiltrating water. Nevertheless, proper manure treatment and
      management are necessary to minimize public health risks.

PMID- 27695749
TI  - Assessment and Synthesis of 50 Years of Published Drainage Phosphorus Losses.
AB  - The prevalence of anthropogenic drainage systems in intensively cropped areas
      across North America combined with the degradation of important freshwater
      resources in these regions has created a critical intersection where
      understanding phosphorus (P) transport in drainage waters is vital. In this
      study, drainage-associated nutrient load data were retrieved and quantitatively
      analyzed to develop a more comprehensive understanding of the P loading and crop
      yield impacts of agronomic management practices within drained landscapes. Using
      the Drain Load table in the MANAGE (Measured Annual Nutrient loads from
      AGricultural Environments) database, the effect of factors such as soil
      characteristics, tillage, and nutrient management on P loading were analyzed.
      Across site-years, generally less than 2% of applied P was lost in drainage
      water, which corroborates the order of magnitude difference between agronomic P
      application rates and P loadings that can cause deleterious water quality
      impacts. The practice of no-till significantly increased drainage dissolved P
      loads compared with conventional tillage (0.12 vs. 0.04 kg P ha). The timing and
      method of P application are both known to be important for P losses, but these
      conclusions could not be verified due to low site-year counts. Findings indicate
      there is a substantial need for additional field-scale studies documenting not
      only P losses in drainage water but also important cropping management, nutrient
      application, soil property, and drainage design impacts on such losses.

PMID- 27695750
TI  - Determination of Sorption Coefficient of Phosphorus Applied for Sugarcane
      Production in Southwestern Florida.
AB  - Phosphorus is among the essential nutrients applied to sugarcane ( L.) fields in
      the form of a fertilizer mixture (N, P, and K) in southwestern Florida. Sorption
      coefficient is used for modeling P movement, and in this study, we hypothesized
      that the sorption coefficient determined using fertilizer mixture (N, P, and K)
      will be significantly different from values determined using KCl and CaCl, the
      electrolytes most commonly used for conducting sorption experiments. Supporting
      electrolytes, 0.01 mol L KCl, 0.005 mol L CaCl, deionized (DI) water, simulated
      Florida rain, and fertilizer mixture prepared in Florida rain were used to
      characterize P sorption. Immokalee (Sandy, siliceous, hyperthermic Arenic
      Alaquods) and Margate (Sandy, siliceous hyperthermic Mollic Psammaquents) are the
      dominant mineral soils used for sugarcane production in southwestern Florida; we
      used the A and B horizons of Margate soil and the A and B horizons of the
      Immokalee soil for sorption experiments in this study. Freundlich sorption
      isotherms described P sorption data. The Freundlich sorption isotherm
      coefficients followed the trend 0.005 mol L CaCl > 0.01 mol L KCl ~ fertilizer
      mixture > simulated Florida rain ~ DI water. Sorption coefficients were used for
      modeling P movement with HYDRUS 1D; similar P results were obtained with the 0.01
      mol L KCl and fertilizer mixture electrolyte treatments. The sorption coefficient
      for DI water and simulated Florida rain overpredicted P movement. The P sorption
      data showed the importance of choosing the appropriate electrolyte for conducting
      experiments based on the composition of fertilizer.

PMID- 27695751
TI  - Responses of Reclamation Plants to High Root Zone pH: Effects of Phosphorus and
      Calcium Availability.
AB  - Low phosphorus (P) availability and high pH inhibit plant growth in calcareous
      soils and some oil sands reclamation sites in northeastern Alberta, Canada. In
      this study, we used a split-root hydroponic setup to test the effects of
      supplemental P with different calcium (Ca) concentrations and root-zone pH
      conditions on the growth and physiological response of trees commonly found in
      the region: paper birch ( Marsh.), trembling aspen ( Michx.), green alder [
      (Chaix) DC.], and black spruce [ (Mill.) Britton, Sterns & Poggenb.] seedlings.
      Plant roots were divided and treated with different combinations of P (0.5 and 15
      mmol L), Ca (2 and 50 mmol L), and pH (5.0 and 9.0) for 6 wk. After that time, we
      measured seedling height, net photosynthesis and transpiration rates, and the
      concentration of chlorophyll and different elements in the leaves. Plant
      responses varied between species; black spruce was most resistant to high pH and
      high Ca concentrations. We did not find any strong beneficial effects of adding P
      to plants subjected to high root zone pH and high Ca concentration. However,
      exposure of part of the root system to low pH alleviated the effects of high pH,
      likely through the improved supply of micronutrients. Because pH conditions are
      often not uniform in disturbed sites and reclamation soils, our findings may help
      improve potential reclamation and phytoremediation strategies for the oil sands,
      bauxite, and coal-combustion residue utilization industries.

PMID- 27695752
TI  - Biochar Properties Influencing Greenhouse Gas Emissions in Tropical Soils
      Differing in Texture and Mineralogy.
AB  - The ability of biochar applications to alter greenhouse gases (GHGs) (CO, CH, and
      NO) has been attracting research interest. However, inconsistent published
      results necessitate further exploration of potential influencing factors,
      including biochar properties, biochar rates, soil textures and mineralogy, and
      their interactions. Two short-term laboratory incubations were conducted to
      evaluate the effects of different biochars: a biochar with low ash (2.4%) and
      high-volatile matter (VM) (35.8%) contents produced under low-temperature (350
      degrees C) traditional kiln and a biochar with high ash (3.9%) and low-VM (14.7%)
      contents produced with a high-temperature (800 degrees C) Flash Carbonization
      reactor and different biochar rates (0, 2, and 4% w/w) on the GHG emissions in a
      loamy-sand Ultisol and a silty-clay-loam Oxisol. In the coarse-textured, low
      buffer Ultisol, cumulative CO and CH emissions increased with increasing VM
      content of biochars; however, CO emission sharply decreased at 83 MUg VM g soil.
      In the fine-textured, high-buffer Oxisol, there were significant positive effects
      of VM content on cumulative CO emission without suppression effects. Regarding
      cumulative NO emission, there were significant positive effects in the Mn-rich
      Oxisol. Ash-induced increases in soil pH had negative effects on all studied GHG
      emissions. Possible mechanisms include the roles biochar VM played as microbial
      substrates, a source of toxic compounds and complexing agents reducing the
      toxicity of soil aluminum and manganese, and the role of biochar ash in
      increasing soil pH affecting GHG emissions in these two contrasting soils.

PMID- 27695753
TI  - Urban Air Pollution in Taiwan before and after the Installation of a Mass Rapid
      Transit System.
AB  - Urbanization causes air pollution in metropolitan areas, coupled with
      meteorological factors that affect air quality. Although previous studies focused
      on the relationships of urbanization, air pollution, and climate change in
      Western countries, this study evaluated long-term variations of air quality and
      meteorological factors in Taiwanese metropolitan areas (Taipei area, Taichung
      City, and Kaohsiung City) and a rural area (Hualien County) between 1993 and
      2012. The influence of a mass rapid transit (MRT) system on air quality was also
      evaluated. Air pollutant concentrations and meteorology data were collected from
      Taiwan Environmental Protection Administration (TEPA) air monitoring stations and
      Central Weather Bureau stations in the surveyed areas, respectively. Analyses
      indicate that levels of air pollution in metropolitan areas were greater than in
      the rural area. Kaohsiung City had the highest levels of O, SO, and particulate
      matter 2.5 or 10 um in diameter (PM and PM). Clear downward trends for CO, NO,
      PM, PM, and especially SO concentrations were found in the surveyed areas,
      whereas O showed no decrease. Both O and PM concentrations showed similar bimodal
      seasonal distributions. Taiwan's air quality has improved significantly since
      1993, indicating the effectiveness of promoting air pollution strategies and
      policies by the TEPA. Air pollution had an obvious improvement in Taipei area
      after the MRT system began operations in 1996. Because global climate may
      potentially affect urban air pollution in Taiwan, further study to clarify the
      mechanisms by which air pollution may affect human health and other biological
      effects is warranted.

PMID- 27695754
TI  - Comparison of the Physical and Chemical Properties of Laboratory and Field-Aged
      Biochars.
AB  - The long-term impact of biochar on soil properties and agronomic outcomes is
      influenced by changes in the physical and chemical properties of biochars that
      occur with time (aging) in soil environments. Fresh biochars, however, are often
      used in studies because aged biochars are generally unavailable. Therefore, a
      need exists to develop a method for rapid aging of biochars in the laboratory.
      The objectives of this study were to compare the physicochemical properties of
      fresh, laboratory-aged (LA), and field-aged (FA) (>=3 yr) biochars and to assess
      the appropriateness of a laboratory aging procedure that combines acidification,
      oxidation, and incubations as a mimic to field aging in neutral or acidic soil
      environments. Twenty-two biochars produced by fast and slow pyrolysis, and
      gasification techniques from five different biomass feedstocks (hardwood, corn
      stover, soybean stover, macadamia nut shells, and switchgrass) were studied. In
      general, both laboratory and field aging caused similar increases in ash-free
      volatile matter (% w/w), cation and anion exchange capacities, specific surface
      area, and modifications in oxygen-containing surface functional groups of the
      biochars. However, ash content increased for FA (18-195%) and decreased for LA
      (22-74%) biochars, and pH decreased to a greater extent for LA (2.8-6.7 units)
      than for FA (1.6-3.8 units) biochars. The results demonstrate that the proposed
      laboratory aging procedure is effective for predicting the direction of changes
      in biochar properties on field aging. However, in the future we recommend using a
      less aggressive acid treatment.

PMID- 27695756
TI  - Influence of Acidification on the Partitioning of Steroid Hormones among
      Filtrate, Filter Media, and Retained Particulate Matter.
AB  - Hormone contamination of aquatic systems has been shown to have deleterious
      effects on aquatic biota. However, the assessment of hormone contamination of
      aquatic environments requires a quantitative evaluation of the potential effects
      of sample preservation on hormone concentrations. This study investigated the
      influence of acidification (pH 2) of surface water samples on the partitioning of
      hormones among filtrate, filter media, and filter-retained particulate matter.
      Hormones were spiked into unpreserved and sulfuric acid-preserved ultrapure water
      and surface water runoff samples. The samples were filtered, and hormones were
      extracted from the filter and filtrate and analyzed by high-performance liquid
      chromatography. Acidification did not influence the partitioning of hormones onto
      the filter media. For the majority of the hormones investigated in this study,
      the partitioning of hormones to the filter-retained particulate matter was not
      influenced by acidification. Acidification increased the partitioning of
      progesterone and melengestrol acetate onto the retained particulate matter (about
      25% for both analytes). Incorporation of an isotopically labeled internal
      standard (ISTD) for progesterone accounted for the loss of progesterone to the
      filter-retained particulates and resulted in accurate concentrations of
      progesterone in the filtrate. The incorporation of an ISTD for melengestrol
      acetate, however, was unable to account for the loss of melengestrol acetate to
      the retained particulates and resulted in underestimations of melengestrol
      acetate in the filtrate. Our results indicate that the analysis of melengestrol
      acetate in acid preserved surface runoff samples should be conducted on the
      filter-retained particulates as well as the filtrate.

PMID- 27695755
TI  - Long-term Effects of Rock Type on Appalachian Coal Mine Soil Properties.
AB  - Rock-derived overburden material is used as a topsoil substitute for reclamation
      of Appalachian coal mines. We evaluated five mixtures ( = 4 each) of sandstone
      (SS) and siltstone (SiS) overburden as topsoil substitutes for 25+ years to
      quantify changes in mine soil properties. The study area was planted only to tall
      fescue [ (Schreb.)], but over 50 herbaceous species invaded over time. Standing
      biomass was highest in early years (5.2-9.3 Mg ha in 1983) and was strongly
      affected by rock type (SS > SiS), declined significantly by 1989 (1.5-2.4 Mg ha),
      and then increased again (2*) by 2008. However, there was no long-term rock type
      effect on standing biomass. Rock fragments and texture differed after 26 yr, with
      fewer rock fragments in the SS-dominated mixtures (53 vs. 77% in SiS) and lower
      sand and higher clay in the SiS-dominated mixtures. Soil pH initially ranged from
      5.45 (SS) to 7.45 (SiS), dropped for several years, increased in all SiS mixes,
      and then slowly declined again to 5.65 (SS) to 6.46 (SiS) over the final 15 yr.
      Total N, organic matter, and cation exchange capacity increased with time, and
      extractable P decreased. Chemical weathering was most apparent initially, but
      physical weathering of rock fragments and changes in texture continued throughout
      the study period. Influences of original rock mixtures remained apparent after
      25+ yr in both physical and chemical properties of these mine soils, which
      remained much coarser than local native soils but were higher in pH, exchangeable
      cations, and extractable P.

PMID- 27695757
TI  - Nutrient Runoff Losses from Liquid Dairy Manure Applied with Low-Disturbance
      Methods.
AB  - Manure applied to cropland is a source of phosphorus (P) and nitrogen (N) in
      surface runoff and can contribute to impairment of surface waters. Tillage
      immediately after application incorporates manure into the soil, which may reduce
      nutrient loss in runoff as well as N loss via NH volatilization. However, tillage
      also incorporates crop residue, which reduces surface cover and may increase
      erosion potential. We applied liquid dairy manure in a silage corn ( L.)-cereal
      rye ( L.) cover crop system in late October using methods designed to incorporate
      manure with minimal soil and residue disturbance. These include strip-till
      injection and tine aerator-band manure application, which were compared with
      standard broadcast application, either incorporated with a disk or left on the
      surface. Runoff was generated with a portable rainfall simulator (42 mm h for 30
      min) three separate times: (i) 2 to 5 d after the October manure application,
      (ii) in early spring, and (iii) after tillage and planting. In the postmanure
      application runoff, the highest losses of total P and dissolved reactive P were
      from surface-applied manure. Dissolved P loss was reduced 98% by strip-till
      injection; this result was not statistically different from the no-manure
      control. Reductions from the aerator band method and disk incorporation were 53
      and 80%, respectively. Total P losses followed a similar pattern, with 87%
      reduction from injected manure. Runoff losses of N had generally similar patterns
      to those of P. Losses of P and N were, in most cases, lower in the spring rain
      simulations with fewer significant treatment effects. Overall, results show that
      low-disturbance manure application methods can significantly reduce nutrient
      runoff losses compared with surface application while maintaining residue cover
      better than incorporation by tillage.

PMID- 27695758
TI  - Polycyclic Aromatic Hydrocarbon Contamination in Soils of San Mateo Ixtatan,
      Guatemala: Occurrence, Sources, and Health Risk Assessment.
AB  - Exposure to high concentrations of carcinogenic pollutants in soils and sediments
      can result in increased health risks. Determining the levels and sources of
      contamination in developing communities is important for helping to reduce
      pollution and mitigate the risk of exposure. In the Mayan community of San Mateo
      Ixtatan, Guatemala, 24 samples of topsoil from urban, peri-urban, and
      agricultural sites and six samples of river sediment were collected and analyzed
      for 17 polycyclic aromatic hydrocarbons (PAHs). The sum of the concentrations of
      these PAHs at the urban and peri-urban sites ranged from 460 to 3251 MUg kg
      (mean, 1401 MUg kg), whereas at agricultural sites the range was 350 to 2087 MUg
      kg (mean, 1038 MUg kg). Analysis to identify and apportion the source showed that
      the PAHs emitted from wood stoves contributed 71 and 76% of the total PAHs in
      urban and agricultural areas soils, respectively. The calculated incremental
      lifetime cancer risk due to the ingestion of soil, dermal contact, and dietary
      intake through corn consumption was greater than the acceptable level of 10
      established by the USEPA. Our findings suggest that the residents of rural
      communities can be at increased cancer risk despite little or no industrial
      activity in the local area. Alternate domestic fuel sources should be considered
      to reduce the health risk in local communities.

PMID- 27695759
TI  - Impact of Kura Clover Living Mulch on Nitrous Oxide Emissions in a Corn-Soybean
      System.
AB  - Nitrous oxide (NO), produced primarily in agricultural soils, is a potent
      greenhouse gas and is the dominant ozone-depleting substance. Efforts to reduce
      NO emissions are underway, but mitigation results have been inconsistent. The
      leguminous perennial kura clover ( M. Bieb.) (KC) can grow side-by-side with cash
      crops in rotational corn ( L.)-soybean ( L.) systems. With biological nitrogen
      fixation, KC provides land managers an opportunity to reduce external fertilizer
      inputs, which may diminish problematic NO emissions. To investigate the effect of
      a KC living mulch on NO emissions, automated soil chambers coupled to a NO
      analyzer were used to measure hourly fluxes from April through October in a 2-yr
      corn-soybean (CS) rotation. Emissions from the KC treatment were significantly
      greater than those from the conventional CS treatment despite the fact that the
      KC treatment received substantially less inorganic nitrogen fertilizer. A
      seasonal tradeoff was observed with the KC treatment wherein emissions before
      strip-tillage were reduced but were surpassed by high losses after strip-tillage
      and postanthesis. These results represent the first reported measurements of NO
      emissions from a KC-based living mulch. The findings cast doubt on the efficacy
      of KC for mitigating NO loss in CS systems. However, if KC reduces nitrate
      leaching losses, as has been reported elsewhere, it may result in lower indirect
      (offsite) NO emissions.

PMID- 27695760
TI  - Methane and Nitrous Oxide Emissions from Cattle Excreta on an East African
      Grassland.
AB  - Greenhouse gas (GHG) emission measurements from livestock excreta in Africa are
      limited. We measured CH and NO emissions from excreta of six Boran () and six
      Friesian () steers near Nairobi, Kenya. The steers were fed one of three diets
      (T1 [chaffed wheat straw], T2 [T1 + Meissner - 0.2% live weight per day], and T3
      [T1 + calliandra - 0.4% live weight every 2 d]). The T1 diet is similar in
      quality to typical diets in the region. Calliandra is a leguminous fodder tree
      promoted as a feed supplement. Fresh feces and urine were applied to grasslands
      and emissions measured using static chambers. Cumulative 28-d fecal emissions
      were 302 +/- 52.4 and 95 +/- 13.8 mg CH-C kg dry matter for Friesen and Boran
      steers, respectively, and 11.5 +/- 4.26 and 24.7 +/- 8.32 mg NO-N kg dry matter
      for Friesian and Boran steers, respectively. For urine from Friesian steers, the
      NO emissions were 2.8 +/- 0.64 mg NO-N 100 mL urine. The CH emission factors
      (EFs) (246 +/- 49.5 and 87 +/- 12.7 g CH-C yr animal for Friesan and Boran,
      respectively) were lower than the International Panel on Climate Change EFs (750
      g CH-C animal yr), whereas the NO EFs (0.1 and 0.2% for the Friesian and Boran
      feces, respectively, and 1.2% for urine) were also lower than International Panel
      on Climate Change estimates. The low N content of the excreta likely caused the
      low emissions and indicates that current models probably overestimate CH and NO
      emissions from African livestock manure.

PMID- 27695761
TI  - Kriging Models Predicting Atrazine Concentrations in Surface Water Draining
      Agricultural Watersheds.
AB  - The performance of kriging methods in predicting maximum m-day (m = 1, 7, 14, or
      30) rolling averages of atrazine concentrations in 42 site-years of Midwest Corn
      Belt watersheds under two systematic sampling designs (sampling every 7 or 14 d)
      was examined. Daily atrazine monitoring data obtained from the Atrazine
      Ecological Monitoring Program in the Corn Belt region (2009-2014) were used in
      the evaluation. Both ordinary and universal kriging methods were considered, with
      the covariate for universal kriging derived from the deterministic Pesticide Root
      Zone Model (PRZM). For the maximum 1-d rolling averages, prediction did not
      differ among methods. For rolling averages of longer duration (m > 1),
      predictions obtained by linear interpolation on a logarithmic scale were better
      (up to 15% lower for 7-d sampling and 22% lower for 14-d sampling in terms of the
      relative root mean squared prediction error) than those obtained by linear
      interpolation on the original linear scale and also less variable. For kriging
      methods, empirical semivariograms of daily atrazine time series suggest a
      negligible noise process, supported by replicate analysis of selected field
      samples; piecewise linear semivariogram models were found to perform best for
      predicting sampled data. We demonstrate that kriging prediction intervals offer
      close to nominal coverage for unsampled values.

PMID- 27695762
TI  - Long-term Impact of Sewage Sludge Application on biovar : An Evaluation Using
      Meta-Analysis.
AB  - The Long-Term Sludge Experiment (LTSE) began in 1994 at nine UK field sites as
      part of continuing research into the effects of sludge-borne heavy metals on soil
      fertility. The long-term effects of Zn, Cu, and Cd on the most probable numbers
      of cells (MPN) of biovar were monitored for 8 yr in sludge-amended soils. To
      assess the statutory limits set by the UK Sludge (Use in Agriculture)
      Regulations, the experimental data were reviewed using statistical methods of
      meta-analysis. Previous LTSE studies have focused predominantly on statistical
      significance rather than effect size, whereas meta-analysis focuses on the
      magnitude and direction of an effect, i.e., the practical significance rather
      than its statistical significance. Results showed Zn to be the most toxic element
      causing an overall significant decrease in MPN of -26.6% during the LTSE. The
      effect of Cu showed no significant effect on MPN at concentrations below the UK
      limits, although a -5% decrease in MPN was observed in soils where total Cu
      ranged from 100 to <135 mg kg. Overall, there was nothing to indicate that Cd had
      a significant effect on MPN below the current UK statutory limit. In summary, the
      UK statutory limit for Zn appears to be insufficient for protecting from Zn
      toxicity effects.

PMID- 27695763
TI  - Co-transport of Pesticide Acetamiprid and Silica Nanoparticles in Biochar-Amended
      Sand Porous Media.
AB  - The role of biochar as a soil amendment on the transport of acetamiprid, a widely
      used neonicotinoid pesticide, is little known. We conducted saturated column
      experiments to examine cotransport of acetamiprid and silica nanoparticles (NPs)
      in pure and biochar-amended sands. Retention of acetamiprid was minor in the pure
      sand, whereas application of biochar in the sand significantly increased
      retention. Retention was greater at lower ionic strengths and near neutral pH
      values and was attributed to biodegradation and sorption through pi-pi
      interaction and pore filling. The convection-diffusion equation with inclusion of
      first-order sorption, desorption, and degradation well described the transport of
      acetamiprid in the biochar-amended sand. The simulation results show that the
      sorption rate did not change with pH. This is because the acetamiprid is nonionic
      and cannot be bonded with the biochar by protonation or deprotonation. The
      desorption rate was independent of variation of solution chemistry, indicating
      that desorption was a physical process (i.e., pore diffusion). Application of
      biochar in the sand had little influence on the transport of silica NPs in NaCl
      but caused complete attachment in CaCl. Energy dispersive X-ray spectroscopy
      suggested that the enhanced attachment was due to cation bridging between silica
      NPs and functional groups in biochar by the Ca. The co-presence of acetamiprid
      and silica NPs in the solutions enhanced transport of acetamiprid and NPs in the
      biochar-amended sand by competing for the binding sites on the biochar surfaces.

PMID- 27695764
TI  - Nitrous Oxide Emissions from a Golf Course Fairway and Rough after Application of
      Different Nitrogen Fertilizers.
AB  - Few studies have quantified nitrous oxide (NO) emissions from intensively managed
      turfgrass systems on golf courses. Fertilizer treatments consisting of urea with
      inhibitors of nitrification and urease (INU), polymer-coated urea (PCU), and
      uncoated balanced methylene urea (BMU) chain, which use different mechanisms to
      control the release of N substrate, were applied to a golf course fairway and
      rough three times during the 2011 growing season at a rate of 50 kg N ha per
      application. The vented chamber method was used to measure turf-soil-atmospheric
      NO exchange. Cumulative emissions from fairway INU, PCU, and BMU treatments
      totaled 6.5, 1.9, and 7.6 kg NO-N ha yr, representing a 4.02, 1.25, and 4.75%
      loss of total N applied, respectively. Summer INU and BMU fertilization to the
      fairway produced the greatest NO fluxes. Rapid fluxes during the summer were
      likely related to low physiological activity in cool-season turfgrass and to
      warm, wet soil conditions that increased denitrification rates. However, PCU
      applied to the fairway was more resistant to NO losses than other fertilizer
      treatments. Fertilizer treatments applied to the rough had cumulative emissions
      of 2.4, 1.50, and 1.49 kg NO-N ha yr from INU, PCU, and BMU treatments,
      corresponding to a 1.21, 0.62, and 0.61% loss of total N applied, respectively.
      The lower NO emission on roughs was likely associated with greater carbon pools,
      lower soil moisture, and lower temperatures. This study supports the
      effectiveness of PCU to reduce NO emission from cool-season turfgrass fairways
      when soil conditions favored denitrification during warm periods. Applying INU
      and BMU when soil was cool and dry was effective in moderating NO losses.

PMID- 27695765
TI  - Decreasing Phosphorus Loss in Tile-Drained Landscapes Using Flue Gas
      Desulfurization Gypsum.
AB  - Elevated phosphorus (P) loading from agricultural nonpoint-source pollution
      continues to impair inland waterbodies throughout the world. The application of
      flue gas desulfurization (FGD) gypsum to agricultural fields has been suggested
      to decrease P loading because of its high calcium content and P sorbing
      potential. A before-after control-impact paired field experiment was used to
      examine the water quality effects of successive FGD gypsum applications (2.24 Mg
      ha; 1 ton acre each) to an Ohio field with high soil test P levels (>480 ppm
      Mehlich-3 P). Analysis of covariance was used to compare event discharge,
      dissolved reactive P (DRP), and total P (TP) concentrations and loadings in
      surface runoff and tile discharge between the baseline period (86 precipitation
      events) and Treatment Period 1 (42 precipitation events) and Treatment Period 2
      (84 precipitation events). Results showed that, after the first application of
      FGD gypsum, event mean DRP and TP concentrations in treatment field tile water
      were significantly reduced by 21 and 10%, respectively, and DRP concentrations in
      surface runoff were significantly reduced by 14%; however, no significant
      reductions were noted in DRP or TP loading. After the second application, DRP and
      TP loads were significantly reduced in surface runoff (DRP, 41%; TP 40%), tile
      discharge (DRP, 35%; TP, 15%), and combined (surface + tile) discharge (DRP, 36%;
      TP, 38%). These findings indicate that surface application of FGD gypsum can be
      used as a tool to address elevated P concentrations and loadings in drainage
      waters.

PMID- 27695766
TI  - Nitrogen Removal in Permeable Woodchip Filters Affected by Hydraulic Loading Rate
      and Woodchip Ratio.
AB  - Unregulated and event-driven agricultural tile drainage discharge poses several
      challenges that potentially limit the nitrate (NO) removal performance of
      woodchip-based wetlands constructed to intercept subsurface tile drain flows.
      Laboratory column tests were conducted to evaluate the biogeochemical response of
      mixed reactive media (woodchips-seashells and woodchips-Filtralite mixtures) at
      two woodchip ratios to changes in hydraulic loading rate (HLR). The tests
      involved continuous loading of aerated artificial drainage water spiked with NO-N
      and tritium (HO) breakthrough experiments. Flow-normalized NO reduction rates
      ranged from 0.35 to 3.97 g N m L, corresponding to N removal efficiencies of 5 to
      64%, depending on HLR and filter mixtures. At high HLRs, oxic conditions
      prevailed in the woodchip filters, resulting in reduced N removal. At low HLRs,
      progressively lower pore-water velocities extended the period for consumption of
      terminal electron acceptors, increasing N removal. When increasing the content of
      mineral material, N removal declined, probably due to a lower denitrifying
      biomass at lower woodchip mass. The effect of woodchip ratios on solute transport
      characteristics was difficult to assess. However, woodchip media including a
      mineral fraction of crushed seashells demonstrated the highest N removal rates
      and efficiencies, most likely due to the alkalizing effect of the seashells. In
      conclusion, filter mixtures consisting of woodchips and seashells were the most
      effective material for N removal in subsurface flow-constructed wetlands treating
      agricultural drainage water.

PMID- 27695767
TI  - Contrasting Nitrogen Fate in Watersheds Using Agricultural and Water Quality
      Information.
AB  - Surplus nitrogen (N) estimates, principal component analysis (PCA), and end
      member mixing analysis (EMMA) were used in a multisite comparison contrasting the
      fate of N in diverse agricultural watersheds. We applied PCA-EMMA in 10
      watersheds located in Indiana, Iowa, Maryland, Nebraska, Mississippi, and
      Washington ranging in size from 5 to 1254 km with four nested watersheds.
      Watershed Surplus N was determined by subtracting estimates of crop uptake and
      volatilization from estimates of N input from atmospheric deposition, plant
      fixation, fertilizer, and manure for the period from 1987 to 2004. Watershed
      average Surplus N ranged from 11 to 52 kg N ha and from 9 to 32% of N input.
      Solute concentrations in streams, overland runoff, tile drainage, groundwater
      (GW), streambeds, and the unsaturated zone were used in the PCA-EMMA procedure to
      identify independent components contributing to observed stream concentration
      variability and the end-members contributing to streamflow and NO load. End
      members included dilute runoff, agricultural runoff, benthic-processing, tile
      drainage, and oxic and anoxic GW. Surplus N was larger in watersheds with more
      permeable soils (Washington, Nebraska, and Maryland) that allowed greater
      infiltration, and oxic GW was the primary source of NO load. Subsurface transport
      of NO in these watersheds resulted in some removal of Surplus N by
      denitrification. In less permeable watersheds (Iowa, Indiana, and Mississippi),
      NO was rapidly transported to the stream by tile drainage and runoff with little
      removal. Evidence of streambed removal of NO by benthic diatoms was observed in
      the larger watersheds.

PMID- 27695768
TI  - Profenofos, an Acetylcholinesterase-Inhibiting Organophosphorus Pesticide: A
      Short Review of Its Usage, Toxicity, and Biodegradation.
AB  - Pesticides play an important role in the protection of different crops. Among the
      diverse sets of pesticides used all over the world, the organophosphates are the
      most widely used group. Profenofos [O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl
      phosphorothioate] is one of the most largely used organophosphate insecticides on
      field crops, vegetables, and fruit crops. The World Health Organization
      classifies this compound as moderately hazardous (Toxicity Class II), and its
      residues have been found in vegetables like okra [ (L.) Moench], gooseberries (
      sp.), green chilies [ (L.)], curry leaves [ (L.) Spreng], mint leaves [ (L.)],
      and coriander leaves [ (L.)]. Dietary intake of profenofos (PFF) is the major
      exposure pathway for humans. When applied to agricultural fields, PFF residues
      spread into every part of the environment: ambient air, surface water, and soil.
      In this review, we discuss the worldwide usage of PFF pesticide, its toxic
      effects on humans and other living organisms in the environment, and
      biodegradation of this chemical by various microbial strains. To date, no
      complete biodegradation pathway has been established for PFF pesticide, calling
      for a study of this nature.

PMID- 27695769
TI  - Surfactant-Modified Soil Amendments Reduce Nitrogen and Phosphorus Leaching in a
      Sand-Based Rootzone.
AB  - United States Golf Association putting greens are susceptible to nitrogen (N) and
      phosphorus (P) leaching. Inorganic soil amendments are used to increase moisture
      and nutrient retention and may influence N and P leaching. This study was
      conducted to determine whether N and P leaching could be reduced using soil
      amendments and surfactant-modified soil amendments. Treatments included a control
      (sand), sand-peat, zeolite, calcined clay, hexadecyltrimethylammonium-zeolite,
      and hexadecyltrimethylammonium-calcined clay. Lysimeters were filled with a 30-cm
      rootzone layer of sand-peat (85:15 by volume), below which a 5-cm treatment layer
      of amendments was placed. A solution of NO-N, NH-N, and orthophosphate-P (2300,
      2480, and 4400 MUg mL, respectively) was injected at the top of each lysimeter,
      and leachate was collected using an autocollector set to collect a 10-mL sample
      every min until four pore volumes were collected. Uncoated amendments, sand, and
      peat had no influence on NO-N retention, whereas hexadecyltrimethylammonium
      coated amendments reduced NO-N leaching to below detectable limits. Both coated
      and uncoated amendments reduced NH-N leaching, with zeolite reducing NH-N leached
      to near zero regardless of hexadecyltrimethylammonium coating. Pure sand resulted
      in a 13% reduction of applied orthophosphate-P leaching, whereas peat contributed
      to orthophosphate-P leaching. Surfactant-modified amendments reduced
      orthophosphate-P leaching by as much as 97%. Surfactant-modified soil amendments
      can reduce NO-N, NH-N, and orthophosphate-P leaching and, thus, may be a viable
      option for removing leached N and P before they enter surface or ground waters.

PMID- 27695770
TI  - High Nitrate Concentrations in Some Midwest United States Streams in 2013 after
      the 2012 Drought.
AB  - Nitrogen sources in the Mississippi River basin have been linked to degradation
      of stream ecology and to Gulf of Mexico hypoxia. In 2013, the USGS and the USEPA
      characterized water quality stressors and ecological conditions in 100 wadeable
      streams across the midwestern United States. Wet conditions in 2013 followed a
      severe drought in 2012, a weather pattern associated with elevated nitrogen
      concentrations and loads in streams. Nitrate concentrations during the May to
      August 2013 sampling period ranged from <0.04 to 41.8 mg L as N (mean, 5.31 mg
      L). Observed mean May to June nitrate concentrations at the 100 sites were
      compared with May to June concentrations predicted from a regression model
      developed using historical nitrate data. Observed concentrations for 17 sites,
      centered on Iowa and southern Minnesota, were outside the 95% confidence interval
      of the regression-predicted mean, indicating that they were anomalously high. The
      sites with a nitrate anomaly had significantly higher May to June nitrate
      concentrations than sites without an anomaly (means, 19.8 and 3.6 mg L,
      respectively) and had higher antecedent precipitation indices, a measure of the
      departure from normal precipitation, in 2012 and 2013. Correlations between
      nitrate concentrations and watershed characteristics and nitrogen and oxygen
      isotopes of nitrate indicated that fertilizer and manure used in crop production,
      principally corn, were the dominant sources of nitrate. The anomalously high
      nitrate levels in parts of the Midwest in 2013 coincide with reported higher-than
      normal nitrate loads in the Mississippi River.

PMID- 27695771
TI  - Alpha-linolenic acid treatment during oocyte maturation enhances embryonic
      development by influencing mitogen-activated protein kinase activity and
      intraoocyte glutathione content in pigs.
AB  - The purpose of this study was to examine the effects of alpha-linolenic acid
      (ALA) treatment during in vitro maturation (IVM) on nuclear maturation,
      intraoocyte glutathione (GSH) content, meiotic progression, and developmental
      competence after parthenogenesis (PA) and somatic cell nuclear transfer (SCNT) in
      pigs. Medium-199 containing 10% (vol/vol) porcine follicular fluid (PFF; PPF
      control) or 0.4% (wt/vol) fatty acid-free BSA (BSA control) was used for IVM. The
      proportion of oocytes reaching the metaphase II (MII) stage was not influenced by
      ALA treatment at various concentrations (50, 100, and 200 MU). However, treatment
      with 100 MU ALA significantly increased ( < 0.05) intraoocyte GSH content (1.19
      vs. 1.00 and 0.92 pixels per oocyte, comparing the treated oocytes, BSA control,
      and PFF control, respectively) and embryonic development to the blastocyst stage
      after PA (47.1 vs. 35.5 and 35.2%) and SCNT (31.4 vs. 23.9 and 24.3%). ALA
      treatment (100 MU) accelerated oocyte maturation, and a higher proportion of ALA
      treated oocytes (89.6%) reached the MII stage than did the untreated controls
      (75.5%) at 33 h of IVM. Mitogen-activated protein kinase kinase inhibitor (U0126)
      treatment during IVM inhibited nuclear maturation and embryonic development after
      PA. However, 100 MU ALA completely counteracted the suppressive effect of U0126
      on nuclear maturation and partially counteracted the effect on blastocyst
      formation. Our results demonstrate that treatment with 100 MU ALA during IVM
      improves developmental competence by accelerating nuclear maturation and also
      influencing cytoplasmic maturation, such as increased GSH content in IVM oocytes.

PMID- 27695772
TI  - Forage use to improve environmental sustainability of ruminant production.
AB  - Ruminants raised for meat and milk are important sources of protein in human
      diets worldwide. Their unique digestive system allows them to derive energy and
      nourishment from forages, making use of vast areas of grazing lands not suitable
      for arable cropping or biofuel production and avoiding direct competition for
      grain that can be used as human food. However, sustaining an ever-growing
      population of ruminants consuming forages poses a dilemma: while exploiting their
      ecological niche, forage-fed ruminants produce large amount of enteric methane, a
      potent greenhouse gas. Resolving this quandary would allow ruminants an expanded
      role in meeting growing global demands for livestock products. One way around the
      dilemma is to devise forage-based diets and feeding systems that reduce methane
      emissions per unit of milk or meat produced. Ongoing research has made
      significant strides toward this objective. A wider opportunity is to look beyond
      methane emissions alone and consider all greenhouse gas emissions from the entire
      livestock-producing system. For example, by raising ruminants in systems using
      forages, some of the methane emissions can be offset by preserving or enhancing
      soil carbon reserves, thereby withholding carbon dioxide from the air. Similarly,
      well-managed systems based on forages may reduce synthetic fertilizer use by more
      effective use of manure and nitrogen-fixing plants, thereby curtailing nitrous
      oxide emissions. The potential environmental benefits of forage-based systems may
      be expanded even further by considering their other ecological benefits, such as
      conserving biodiversity, improving soil health, enhancing water quality, and
      providing wildlife habitat. The quandary, then, can be alleviated by managing
      ruminants within a holistic land-livestock synchrony that considers not only
      methane emissions but also suppression of other greenhouse gases as well as other
      ecological benefits. Given the complexity of such systems, there likely are no
      singular "best-management" practices that can be recommended everywhere. Using
      systems-based approaches such as life cycle analysis, ruminant production can be
      tuned for local lands to achieve greatest net benefits overall. In many
      instances, such systems, based on forages, may maintain high output of milk and
      meat while also furnishing other ecosystem benefits, such as reduced overall
      greenhouse gas emissions.

PMID- 27695773
TI  - Influence of oral glucosamine supplementation in young horses challenged with
      intra-articular lipopolysaccharide.
AB  - Fourteen yearling Quarter horses (351 to 470 kg) were utilized in a randomized
      complete block design to evaluate potential of glucosamine hydrochloride (HCl) to
      mitigate intra-articular inflammation following a single inflammatory insult.
      Horses were blocked by BW, age, and sex, and randomly assigned to treatments for
      a 98-d experiment. Treatments consisted of a control diet (CON; = 7) fed 1% BW
      per d (as-fed) of concentrate only or a treatment diet ( = 7) of concentrate top
      dressed with 30 mg/kg BW glucosamine HCl (99.6% purity; GLU30) offered at 12 h
      intervals. Horses were maintained in individual stalls and offered approximately
      1% BW per d of coastal bermudagrass hay (). Plasma and synovial fluid samples
      were obtained every 14 and 28 d, respectively, and stored at -20 degrees C,
      before analysis of glucosamine via HPLC. On d 84, an intra-articular
      lipopolysaccharide (LPS) challenge was conducted on all horses to determine
      ability of dietary glucosamine HCl supplementation to mitigate joint inflammation
      and cartilage metabolism. Carpal joints were randomly selected to receive 1 of 2
      intra-articular treatments and included sterile lactated Ringer's (control;
      Contra) only or 0.5 ng LPS solution (LPS) obtained from O55:B5 into the radial
      carpal joint. Synovial fluid was obtained at pre-injection h 0 and 6, 12, 24,
      128, and 336 h post-injection, and was analyzed for prostaglandin E (PGE),
      carboxypeptide of type II collagen (CPII) and collagenase cleavage neopeptide
      (C2C) biomarkers by commercial ELISA kits. Data were analyzed using PROC MIXED
      procedure of SAS. Plasma and synovial glucosamine tended ( = 0.10 and = 0.06,
      respectively) to increase over time in response to GLU30 compared to CON. There
      was a treatment by time interaction ( <= 0.01), with GLU30 increasing plasma
      glucosamine concentrations at 28 and 42 d when compared to CON. A treatment by
      time interaction ( <= 0.01) was observed with GLU30 increasing synovial
      glucosamine levels at d 28 and 84 ( <= 0.01 and = 0.05, respectively). Intra
      articular LPS increased ( <= 0.01) synovial PGE, C2C, and CPII levels. GLU30
      decreased synovial PGE and C2C concentrations when compared to CON ( = 0.04 and =
      0.05, respectively), while synovial levels of CPII increased ( <= 0.01) in GLU30
      horses. These results indicate the potential for oral glucosamine HCl to mitigate
      intra-articular inflammation and influence cartilage turnover in a young horse
      model.

PMID- 27695774
TI  - Can a super sow be a robust sow? Consequences of litter investment in purebred
      and crossbred sows of different parities.
AB  - The aim of this project was to study the consequences of litter investment on
      physical characteristics in primiparous and multiparous sows in 3 Norwegian
      breeds (Norsvin Duroc [ = 12], Norsvin Landrace [ = 12], and crossbreeds [Norsvin
      Landrace and Swedish Yorkshire { = 15}]). We predicted that the maternal sow line
      (Norsvin Landrace) would invest more in their litter in term of higher weight at
      birth, resulting in a higher litter weight of weaned piglets but with the
      consequence of greater loss in body condition and a higher prevalence of shoulder
      lesions. It was predicted that this should be more pronounced in primiparous sows
      than in multiparous sows. As predicted, the maternal pure line (Norsvin Landrace)
      had higher litter investment in terms of litter weight at birth ( = 0.003) and
      litter weight at weaning ( = 0.050) as well as higher total litter investment
      (litter weight at weaning plus weight of dead piglets [stillborn and mummified
      piglets and weight of piglets that died after farrowing but before weaning]; =
      0.050) and suffered larger losses of body condition ( = 0.016) and had a higher
      prevalence of shoulder lesions ( = 0.008) during lactation than other breeds.
      Moreover, only in Norsvin Landrace was development of shoulder lesions related to
      inadequate feed consumption ( = 0.006). This has become a major welfare concern
      of modern pig breeding. Although primiparous and multiparous sows had similar
      litter sizes, primiparous sows had lower litter investment in terms of litter
      weight at birth ( = 0.032) and litter weight at weaning ( = 0.007) as well as
      total litter investment ( = 0.008). Primiparous sows suffered greater losses in
      body condition ( = 0.012) and developed more shoulder lesions ( = 0.026) due to
      lower total feed consumption ( < 0.001) during lactation than multiparous sows.
      Especially in the highly productive maternal line (Norsvin Landrace), development
      of shoulder lesions during the lactation period was more pronounced in
      primiparous sows than in multiparous sows ( < 0.001). The selection program has
      shifted the balance to greater investments in earlier life, when sows still need
      resources for their own growth and development. This has resulted in a larger
      number of weaned piglets but at a higher sow welfare cost in terms of higher
      losses in body condition and a higher prevalence of shoulder lesions. Our results
      pinpoint the importance of improving the balance between economic traits and
      traits that improve welfare and longevity of the sows.

PMID- 27695775
TI  - Effects of wheat source and particle size in meal and pelleted diets on finishing
      pig growth performance, carcass characteristics, and nutrient digestibility.
AB  - Two experiments were conducted to test the effects of wheat source and particle
      size in meal and pelleted diets on finishing pig performance, carcass
      characteristics, and diet digestibility. In Exp. 1, pigs (PIC 327 * 1050; = 288;
      initially 43.8 kg BW) were balanced by initial BW and randomly allotted to 1 of 3
      treatments with 8 pigs per pen (4 barrows and 4 gilts) and 12 pens per treatment.
      The 3 dietary treatments were hard red winter wheat ground with a hammer mill to
      728, 579, or 326 MUm, respectively. From d 0 to 40, decreasing wheat particle
      size decreased (linear, < 0.033) ADFI but improved (quadratic, < 0.014) G:F. From
      d 40 to 83, decreasing wheat particle size increased (quadratic, < 0.018) ADG and
      improved (linear, < 0.002) G:F. Overall from d 0 to 83, reducing wheat particle
      size improved (linear, < 0.002) G:F. In Exp. 2, pigs (PIC 327 * 1050; = 576;
      initially 43.4 +/- 0.02 kg BW) were used to determine the effects of wheat source
      and particle size of pelleted diets on finishing pig growth performance and
      carcass characteristics. Pigs were randomly allotted to pens, and pens of pigs
      were balanced by initial BW and randomly allotted to 1 of 6 dietary treatments
      with 12 replications per treatment and 8 pigs/pen. The experimental diets used
      the same wheat-soybean meal formulation, with the 6 treatments using hard red
      winter or soft white winter wheat that were processed to 245, 465, and 693 MUm
      and 258, 402, and 710 MUm, respectively. All diets were pelleted. Overall,
      feeding hard red winter wheat increased ( < 0.05) ADG and ADFI when compared with
      soft white winter wheat. There was a tendency ( < 0.10) for a quadratic particle
      size * wheat source interaction for ADG, ADFI, and both DM and GE digestibility,
      as they were decreased for pigs fed 465-MUm hard red winter wheat and were
      greatest for pigs fed 402-MUm soft white winter wheat. There were no main or
      interactive effects of particle size or wheat source on carcass characteristics.
      In summary, fine grinding hard red winter wheat fed in meal form improved G:F and
      nutrient digestibility, whereas reducing particle size of wheat from
      approximately 700 to 250 MUm in pelleted diets did not influence growth or
      carcass traits. Finally, feeding hard red winter wheat improved ADG and ADFI
      compared with feeding soft white winter wheat.

PMID- 27695776
TI  - The effects of dietary supplementation of microencapsulated and the extract of
      seed on growth performance, immune functions, and serum biochemical parameters in
      broiler chickens.
AB  - This experiment was conducted to investigate the effects of microencapsulted
      (MEF) and the extract of seed (ECOS) on growth performance, immune functions, and
      serum biochemical parameters in broiler chickens. A total of 240 1-d-old male
      broilers were randomly allotted into 6 treatments with 8 replicates/treatment and
      5 broilers in each cage. The dietary treatments included 1) a basal diet without
      antibiotic (group A), 2) the basal diet + 1 g MEF/kg diet (1 * 10 cfu/g MEF;
      group B), 3) the basal diet + 300 mg ECOS/kg diet (group C), 4) the basal diet +
      300 mg ECOS/kg diet + 1 g MEF/kg diet (group D), 5) the basal diet + 500 mg
      ECOS/kg diet (group E), and 6) the basal diet + 500 mg ECOS/kg diet + 1 g MEF/kg
      diet (group F). The feeding experiment included 2 phases: the starter phase from
      Day 1 through 21 and the grower phase from Day 22 through 42. The results showed
      that a diet supplemented with MEF and ECOS had no significant effect on ADG,
      ADFI, feed conversion ratio, and average BW during the whole experimental period
      ( > 0.05), but group F showed an improving trend in growth performance. Serum IL
      2, IgA, and IgG levels and spleen index were significantly affected by dietary
      treatment ( < 0.05). Serum IgA and IgG levels and spleen index in group F were
      significantly higher than in the group A ( < 0.05), and the IL-2 level was
      significantly decreased ( < 0.05) on Days 21 and 42. Compared with the group A,
      diets supplemented with MEF and ECOS can significantly decrease total
      cholesterol, low-density lipoprotein cholesterol, triglycerides, and blood urea
      nitrogen levels ( < 0.05) and increase the high-density lipoprotein cholesterol
      level on Days 21 and 42. Concentrations of serum biochemical parameters were
      significantly increased in group F ( < 0.05). In summary, the results indicated
      that dietary supplementation of MEF and/or ECOS had no significant effect on
      growth performance but significantly increased spleen index and the levels of
      serum IgA and IgG and improved serum lipid metabolism. The 1 g MEF/kg diet (1 *
      10 cfu/g diet) plus 500 mg ECOS/kg diet was the optimum supplemental dose in this
      experiment.

PMID- 27695777
TI  - Genetic relationships between boar feed efficiency and sow piglet production,
      body condition score, and stayability in Norwegian Landrace pigs.
AB  - Both feed efficiency and sow production are economically important traits in pig
      breeding. One challenge in a maternal line such as Norwegian Landrace is to breed
      for highly feed efficient fattening pigs and, at the same time, produce sows with
      high daily feed intake to maintain their BCS in multiple parities. The aim of
      this study was to estimate genetic correlations among novel feed efficiency
      measurements on Norwegian Landrace boars and piglet production, stayability, and
      body condition in Norwegian Landrace sows. The feed efficiency measurements were
      lean meat and fat efficiency. These measurements were calculated using an
      extended residual feed intake model where total feed intake in the test period
      was the response variable and fat (kg) and lean meat (kg) on the carcass were
      included as both fixed and random regressions. The random regression coefficients
      that resulted from this model were breeding values, which represented the amount
      of feed used to produce an extra kilogram of lean meat and fat. The sow traits
      were stayability of the sow from first to second parity, BCS at weaning, litter
      weight at 3 wk, and total number of piglets born. All traits were recorded on
      first parity purebred Norwegian Landrace and analyzed using multivariate animal
      models. All genetic correlations between fat efficiency and sow traits were low.
      Significant genetic correlations were found only between fat efficiency and
      stayability (0.21 +/- 0.11) and between fat efficiency and total litter weight at
      3 wk (0.21 +/- 0.10). The results indicate that selection for efficient
      deposition of fat could give poor stayability and lower litter weight at 3 wk in
      first parity sows. The genetic correlations between lean meat efficiency and sow
      traits were not significantly different from 0 and signified no genetic
      relationships between these traits. Selection for efficient deposition of lean
      meat should not affect the sow traits and is, therefore, beneficial.

PMID- 27695778
TI  - Net macromineral requirements in male and female Saanen goats.
AB  - These experiments estimated Ca, P, Mg, K, and Na requirements of intact male,
      castrated male, and female Saanen goats. Two experiments were performed: one to
      determine the net macromineral requirements for maintenance (Exp. 1) and another
      to determine net macromineral requirements for growth (Exp. 2). In Exp. 1, 75
      goats (26 intact males, 25 castrated males, and 24 females) with initial BW (iBW)
      of 15.76 +/- 0.10 kg were used. These animals were divided in 2 groups: baseline
      animals and pair-fed animals. Twenty-one goats (8 intact males, 7 castrated
      males, and 6 females) were slaughtered (16.6 +/- 0.96 kg BW) at the beginning of
      the experiment to be used as the baseline group. The 54 remaining goats (18
      intact males, 18 castrated males, and 18 females) were pair fed in 6 blocks of 3
      goats per sex. The goats within each block were then randomly allocated to 1 of 3
      levels of intake: ad libitum, restricted fed to 75% of the ad libitum intake, and
      restricted fed to 50% of ad libitum intake. When the animal fed ad libitum
      reached 31.2 +/- 0.58 kg BW, it and the other goats from the same block were
      slaughtered. The effects of sex and level of intake were evaluated in a split
      plot design, where sex was the main plot observation and level of intake was the
      subplot. Daily net macromineral requirements for maintenance did not differ among
      the sexes ( > 0.05), and the average values obtained were 35.4 mg Ca, 24.7 mg P,
      2.5 mg Mg, 5.0 mg K, and 3.30 mg Na per kg BW?d. The net requirements for growth
      in Exp. 2 were obtained using 58 goats (20 intact males, 20 castrated males, and
      18 females) with 15.8 +/- 0.11 kg iBW, all fed ad libitum. These animals were
      assigned in a completely randomized design and allocated in 3 slaughter weight
      groups: 16.6 +/- 0.96, 23.1 +/- 1.33, and 31.2 +/- 0.58 kg BW. The net Ca, P, and
      Mg requirements for growth were not different among the sexes ( > 0.05). There
      was a sex effect on net K and Na requirements for growth ( < 0.05). The net K
      requirements for growth (g/kg ADG) of intact males were greater ( = 0.03) and
      increased approximately 16%, whereas females and castrated males decreased
      approximately 11% as BW increased from 15 to 30 kg BW. The net Na requirements
      for growth (g/kg ADG) increased 9.5% for intact males and decreased 22% for
      females when the goats grew from 15 to 30 kg BW. Sex, therefore, affects net K
      and Na requirements for growth, but it does not affect net macromineral
      requirements for maintenance in Saanen goats.

PMID- 27695779
TI  - Deduction of a calcium ion circuit affecting rooster sperm in vitro.
AB  - Four premises for rooster sperm preservation were outlined previously.
      Understanding mitochondrial Ca cycling in terms of whole-cell Ca flux was one
      premise. The present work tested the hypothesis that sperm mitochondria can be
      damaged by intracellular as well as extracellular Ca. Sperm were washed by
      centrifugation through 12% (wt/vol) Sperm were washed by centrifugation through
      12%(at/vol) Accudenz to procure sperm at a physiological concentration within a
      chemically-defined suspension. Five solutions were tested. Each solution
      contained 30 m glucose, and had an osmolality of 320 mmol/kg and a pH of 7.4.
      Washed sperm were diluted to 2.0 * 10 sperm/mL. Each replicate sperm suspension
      was cooled to 10 degrees C. Sperm mobility was measured after 1, 2, 4, 8, 12, and
      24 h. Data were plotted as a function of time in each experiment. Function type
      was confirmed by lack of fit analysis. A parabola with a maximum at 3.7 h was
      observed when sperm were suspended in 205 m taurine buffered with 50 m
      tris[hydroxyl-methyl]methyl-2-amino-ethanesulfonic acid (TES). This effect was
      attributed to a Ca flux from the nuclear envelope into mitochondria. An
      exponential decay was observed when TES-buffered taurine contained 2 m Ca. This
      effect was attributed to mitochondrial Ca overload induced by uptake of
      extracellular Ca. Exponential decay also was observed when TES-buffered taurine
      contained a Ca chelator. This effect was attributed to a Ca flux from the nuclear
      envelope through mitochondria and then into an extracellular Ca sink. This
      possibility was supported by the response of sperm to thapsigargin. Specifically,
      inhibition of sarcoendoplasmic reticulum Ca-ATPase compromised sperm mobility
      relative to a buffer control. Finally, a 60 m phosphate buffer containing 2 m
      citrate yielded a linear relationship in contrast to the TES-buffered solutions
      tested. Sperm mobility after 24 h of storage in the phosphate buffer was 92% of
      that observed for prewashed sperm. The linear response was attributed to weak
      chelators providing resistance within a Ca circuit and thereby preventing
      mitochondrial Ca overload. Fertility, however, was compromised when hens were
      inseminated with mobile sperm recovered after either 8 or 24 h of storage at 10
      degrees C. In conclusion, sperm cell Ca homeostasis was proven to be critical for
      maintaining sperm mobility in vitro, but mitochondrial Ca uptake is not the sole
      phenomenon that compromises sperm function during in vitro storage.

PMID- 27695780
TI  - Technical note: Impact of a molasses-based liquid feed supplement on the feed
      sorting behavior and growth of grain-fed veal calves.
AB  - This study was designed to determine the effect of adding a molasses-based liquid
      feed (LF) supplement to a high-grain mixed ration on the feed sorting behavior
      and growth of grain-fed veal calves. Twenty-four Holstein bull veal calves (90.2
      +/- 2.6 d of age, weighing 137.5 +/- 16.9 kg) were split into groups of 4 and
      exposed, in a crossover design with 35-d periods, to each of 2 treatment diets:
      1) control diet (76.0% high-moisture corn, 19.0% protein supplement, and 5.0%
      alfalfa/grass haylage) and 2) LF diet (68.4% corn, 17.1% protein supplement, 9.0%
      molasses-based LF, and 4.5% alfalfa/grass haylage). Diets were designed to
      support 1.5 kg/d of growth. Data were collected for the final 3 wk of each
      treatment period. Feed intakes were recorded daily and calves were weighed 2
      times/wk. Feed samples of fresh feed and refusals were collected 3 times/wk for
      particle size analysis. The particle size separator had 3 screens (19, 8, and
      1.18 mm) and a bottom pan, resulting in 4 fractions (long, medium, short, and
      fine). Sorting was calculated as the actual intake of each fraction expressed as
      a percent of its predicted intake. Calves tended ( = 0.08) to sort for long
      particles on the control diet (110.5%) and did not sort these particles on the LF
      diet (96.8%). Sorting for medium particles (102.6%) was similar ( = 0.9) across
      diets. Calves sorted against short particles on the LF diet (97.5%; = 0.04) but
      did not sort this fraction on the control diet (99.4%). Calves sorted against
      fine particles (79.3%) to a similar extent ( = 0.2) on both diets. Dry matter
      intake was similar across diets (6.1 kg/d; = 0.9), but day-to-day variability in
      DMI was greater (0.5 vs. 0.4 kg/d; = 0.04) when calves were fed the control
      compared with the LF diet. Calves on both diets had similar ADG (1.6 kg/d; = 0.8)
      as well as within-pen variability in ADG (0.4 kg/d; = 0.7). The feed-to-gain
      ratio was also similar between control and LF diets (4.3 vs. 3.9 kg DM/kg gain; =
      0.4). The results suggest that supplementation of a molasses-based LF to high
      grain fattening veal calf diets can reduce variability in feed consumption, both
      within and across days.

PMID- 27695781
TI  - Investigation of the physiological, behavioral, and biochemical responses of
      cattle to restraint stress.
AB  - Stresses imposed on livestock have significant impact on their health and
      productivity as well as public perceptions of animal welfare. Understanding
      stress responses in livestock may help refine management procedures and
      facilitate selection of stress-tolerant animals. In this study, behavioral (chute
      entry order, chute behavior, and exit velocity), physiological (serum cortisol),
      and biochemical (kinome) responses were evaluated in cattle ( = 20) subjected to
      three 5-min restraint periods with weekly intervals. Correlations among stress
      responses were assessed across all animals as well as for subgroups ( = 4)
      representing animals consistently displaying a high and low extreme of serum
      cortisol responses. Across all animals, entry order ( = 0.006) and exit velocity
      ( = 0.023) were positively correlated with serum cortisol; however, these
      correlations were not consistently reproducible for the high and low serum
      cortisol responders. Kinome profiling of peripheral blood mononuclear cells
      revealed distinct signaling events between the high and low cortisol responders.
      In particular, kinome profiling revealed significant differences in carbohydrate
      metabolism and apoptosis that were independently validated. Furthermore, changes
      in serum glucose levels provided a reliable, inexpensive indicator of serum
      cortisol levels and often had greater predictive value than cortisol for stress
      related behavioral responses. Serum cortisol levels displayed a pattern
      consistent with sensitization, whereas no habituation or sensitization was
      observed for serum glucose levels or behavioral responses. Collectively, this
      investigation provides insight into correlations among physiological, behavioral,
      and biochemical responses of cattle subjected to a brief restraint that may
      provide biomarkers for selection of stress-tolerant animals.

PMID- 27695782
TI  - Transcriptomic signature of high dietary organic selenium supplementation in
      sheep: A nutrigenomic insight using a custom microarray platform and gene set
      enrichment analysis.
AB  - The objective of this study was to investigate the effect of a high dietary Se
      supplementation on the whole transcriptome of sheep. A custom sheep whole
      transcriptome microarray, with more than 23,000 unique transcripts, was designed
      and then used to profile the global gene expression of sheep after feeding a high
      dietary supplementation of organic Se. Lactating crossbred ewes ( = 10; 3 to 4 yr
      of age and 55 to 65 kg BW) at late lactation (100 +/- 8 d in milk) were
      acclimated to indoor individual pen feeding of a basal control diet (0.40 mg
      Se/d, sodium selenite) for 4 wk. Sheep were then kept on a diet with an extra
      (high) supplementation of organic Se (1.45 mg Se/d as Sel-Plex; Alltech
      Biotechnology Pty Ltd, Dandenong, Victoria, Australia) for 40 d. Whole blood was
      collected at 2 time points (last day of the acclimatization period [T0] and after
      40 d of the organic Se supplementation [T40]), and then total RNA was isolated
      and labeled for the subsequent microarray analysis. Significance Analysis of
      Microarrays, using the -statistic, of the microarray data (T40 versus T0)
      evidenced the up- and downregulation of 942 and 244 transcripts (false discovery
      rate < 0.05), respectively. Seven genes showed the same trend of expression (up-
      or downregulation) when tested by quantitative real-time PCR (qPCR) in a cross
      validation step. The microarray showed significant upregulation of the following
      selenoproteins at T40: selenium binding protein 1 (SELENBP1), selenoprotein W1
      (SEPW1), glutathione peroxidase 3 (GPX3), and septin 8 (SEPT8). And the
      expression trends for SEPW1 and SEPT8 were validated using qPCR. Functional
      annotation of the differentially expressed genes showed the enrichment of several
      immune system-related biological processes (lymphocyte activation, cytokine
      binding, leukocyte activation, T cell differentiation, and B cell activation) and
      pathways (cytokine and interleukin signaling). Moreover, Gene Set Enrichment
      Analysis evidenced the enrichment of B and T cell receptors signaling pathways,
      with an enrichment score of 0.63 and 0.59, respectively. Overall, from a global
      gene expression (whole-transcriptome) point of view, short-term supplementation
      of a high dietary organic Se to Se-nondeficient sheep results in a transcriptomic
      signature that mainly reflects an induced immune system and a modulation of
      transcription effect. Also, the present study provides a custom whole
      transcriptome microarray platform that can be used in further global gene
      expression studies in the ovine species.

PMID- 27695783
TI  - Relationships between prenatal ewe traits, milk production, and preweaning
      performance of twin lambs.
AB  - There is limited information on factors affecting twin lamb growth before
      weaning, which limits the options available to farmers to actively manage lamb
      growth. Data from 2 multiyear experiments involving 402 twin-bearing Romney ewes
      were used to evaluate the effects of prenatal ewe traits (live weight at mating
      and set stocking and BCS at mating and set stocking) and combined twin lamb birth
      weight on ewe milk production and lamb growth from birth to weaning as well as
      the proportion of variation in twin lamb growth that could be explained by these
      variables. Additionally, the effect of accumulated ewe milk yield over a 42-d
      period (MY; Days 0 to 42) and accumulated milk components (protein, fat, and
      lactose) on twin lamb growth were investigated. The effects of prenatal variables
      on MY, birth weight, and combined twin lamb live weight gain from Day 0 to 42
      (LWG) were inconsistent across the 2 experiments. In addition, prenatal ewe
      traits ( < 0.05) explained less than 30% of the variation in MY and lamb growth
      from birth to weaning in both experiments. Combined twin lamb birth weight was
      positively ( < 0.001) correlated with MY ( = 0.34 and = 0.43 in Exp. 1 and 2,
      respectively). Combined twin lamb LWG was dependent on ewe MY ( = 0.43 for Exp. 1
      and = 0.30 for Exp. 2). Lactose, fat, and milk CP yields explained 47 and 42% of
      the variation in lamb LWG in Exp. 1 and 2, respectively. Lactose and milk CP
      yield positively affected ( < 0.05) LWG in Exp. 1 and 2, respectively. Fat yield
      had a positive relationship with LWG in Exp. 1 and a negative relationship with
      LWG in Exp. 2. In conclusion, the measured prenatal ewe traits had a minimal
      effect on milk yield and twin lamb growth to weaning. Milk yield and composition
      explained the greatest proportion of variation in LWG. This suggests that farmers
      should select ewes with higher milk yields to maximize twin lamb growth to
      weaning. However, less than 50% of the variation in LWG and weaning live weight
      was explained by the measured ewe and lamb parameters. Therefore, further studies
      are required to determine additional ewe or lamb variables that control variation
      in twin lamb growth.

PMID- 27695784
TI  - The effects of increasing supplementation of zinc-amino acid complex on growth
      performance, carcass characteristics, and inflammatory response of beef cattle
      fed ractopamine hydrochloride.
AB  - Forty-two Angus crossbred steers (380 +/- 5.3 kg) were enrolled in a finishing
      study to evaluate the influence of a supplemental Zn amino-acid complex (ZnAA;
      Availa-Zn) on performance and carcass characteristics of finishing steers in
      combination with ractopamine hydrochloride (RAC). Steers were stratified by BW
      into 7 pens of 6 steers each, and individual feed intake was measured. Steers
      were assigned to 1 of 4 treatments for 86 d (pre-RAC period): a dry-rolled corn
      based diet supplemented with 60 mg Zn/kg DM from ZnSO and no supplemental ZnAA
      (CON; analyzed 88 mg Zn/kg DM; = 6) or CON diet supplemented with 30 (Zn30; =
      12), 60 (Zn60; = 12), or 90 (Zn90; = 11) mg Zn/kg DM from ZnAA. Day 86 BW and G:F
      displayed a quadratic tendency ( = 0.09) with Zn60 steers being greater than the
      other treatments. Plasma cyclic adenosine monophosphate tended to linearly
      increase with increasing ZnAA ( = 0.10). On d 88, 6 of 12 steers (one of the 2
      pens) receiving supplemental ZnAA was randomly selected to be supplemented with
      RAC at 300 mg?steer?d for the final 28 d of the experiment (RAC period). This
      created 7 final treatments: CON: no supplemental ZnAA, no RAC ( = 5); Zn30: Zn30,
      no RAC ( = 5); Zn30R: Zn30 + RAC ( = 6); Zn60: Zn60, no RAC ( = 6); Zn60R: Zn60 +
      RAC ( = 6); Zn90: Zn90, no RAC ( = 5); and Zn90R: Zn90 + RAC ( = 6). During the
      RAC period, as supplemental ZnAA increased within RAC-supplemented treatments,
      there was a linear increase in final BW, ADG, and G:F ( < 0.05). However, there
      was no effect of supplemental ZnAA on BW, ADG, or G:F during this period in non
      RAC fed steers ( >= 0.44). Day 111 plasma Cu was increased, plasma Fe decreased,
      and leukocyte counts and serum interleukin-8 concentrations were greater ( <
      0.05) in RAC-fed steers suggesting that RAC may elicit a mild inflammatory
      response. There was a tendency for increasing Zn supplementation to decrease
      plasma haptoglobin within RAC-fed steers ( = 0.07), suggesting that Zn may alter
      the inflammatory response. Overall, Zn60 improved growth performance during the
      pre-RAC period. Zinc supplemented as ZnAA appears to improve growth in
      combination with RAC supplementation, suggesting that Zn may enhance or support
      the biological function of RAC. Additionally, these results indicate that feeding
      RAC impacts trace mineral status, and potentially causes a non-specific
      inflammatory response, but further research is required to define this response.

PMID- 27695785
TI  - Dietary linseed oil with or without malate increases conjugated linoleic acid and
      oleic acid in milk fat and and gene expression in mammary gland and milk somatic
      cells of lactating goats.
AB  - Supplementary dietary plant oils have the potential to alter milk fatty acid
      composition in ruminants as a result of changes in the amount and kind of fatty
      acid precursors. We hypothesized that linseed oil in combination with malate (a
      key propionate precursor in the rumen) would increase ?9 unsaturated fatty acids
      and specific gene expression in somatic cells and mammary glands of lactating
      goats. Twelve lactating goats were used in a 3 * 3 Latin square design.
      Treatments included the basal diet (CON), the CON plus 4% linseed oil (LO), and
      the CON plus 4% linseed oil and 2% -malate (LOM). Relative to CON, the LO and LOM
      supplements increased the daily intake of palmitic (16:0), stearic (18:0), oleic
      (18:1-9), linoleic (18:2-6), alpha-linolenic (18:3-3), and gamma-linolenic acids
      (18:2-6); alpha-linolenic acid intake was increased over 9-fold, from 6.77 to
      over 51 g/d ( < 0.02). The LO and LOM supplements increased daily milk yield,
      milk fat yield, and milk fat percentage ( < 0.05). The LOM supplement also
      increased milk lactose percentage and daily yield ( = 0.03). Both the LO and LOM
      supplements increased plasma glucose and total cholesterol and decreased plasma
      beta-hydroxbutyrate concentrations ( = 0.03). The LO and LOM supplements
      increased concentrations of stearic acid; -vaccenic acid (TVA; 18:1-11); -9, -11
      CLA; -10 -12 CLA; and alpha-linolenic acid in rumen fluid and increased the
      concentrations of oleic acid; TVA; -9, -11 CLA; -10, -12 CLA; and alpha-linolenic
      acid in plasma lipids and milk fat ( < 0.05). Conversely, the LO and LOM
      supplements decreased short- and medium-chain SFA, including lauric (12:0),
      myristic (14:0), and palmitic acids, in plasma and milk fat ( < 0.05). Relative
      mRNA levels for and () gene expression were increased in somatic cells and
      mammary gland tissue by LO and LOM ( < 0.05). We conclude that the higher intake
      and ruminal production of stearic acid promoted SCD gene expression in somatic
      cells and mammary tissue. Furthermore, milk somatic cells are a suitable
      substitute for documenting treatment effects of dietary oils on gene expression
      in goat mammary tissue.

PMID- 27695786
TI  - Requirement for digestible calcium by eleven- to twenty-five-kilogram pigs as
      determined by growth performance, bone ash concentration, calcium and phosphorus
      balances, and expression of genes involved in transport of calcium in intestinal
      and kidney cells.
AB  - Two experiments were conducted to determine the requirement for standardized
      total tract digestible (STTD) Ca by 11- to 25-kg pigs based on growth
      performance, bone ash, or Ca and P retention and to determine the effect of
      dietary Ca on expression of genes related to Ca transport in the jejunum and
      kidneys. Six diets were formulated to contain 0.36% STTD P and 0.32, 0.40, 0.48,
      0.56, 0.64, or 0.72% STTD Ca by including increasing quantities of calcium
      carbonate in the diets at the expense of cornstarch. Two additional diets
      contained 0.72% STTD Ca and 0.33% or 0.40% STTD P to determine if 0.36% STTD P
      had negative effects on the Ca requirement. The same batch of all diets was used
      in both experiments. In Exp. 1, 256 pigs (11.39 +/- 1.21 kg initial BW) were
      randomly allotted to the 8 diets with 4 pigs per pen and 8 replicate pens per
      diet in a randomized complete block design. On the last day of the experiment, 1
      pig from each pen was euthanized and the right femur and intestine and kidney
      samples were collected. Results indicated that ADG and G:F started to decline
      (linear and quadratic, < 0.05) at 0.54 and 0.50% STTD Ca, respectively. In
      contrast, bone ash increased (quadratic, < 0.05) as dietary Ca increased and
      reached a plateau indicating that the requirement for STTD Ca to maximize bone
      ash was 0.48%. Bone ash, but not ADG or G:F, increased (linear, < 0.01) as STTD
      increased in the diets. The mRNA expression of genes related to transcellular Ca
      transport decreased (linear, < 0.01) in the jejunum and in kidneys (linear and
      quadratic, < 0.01) as dietary Ca increased. In Exp. 2, 80 pigs (13.12 +/- 1.79 kg
      initial BW) were placed in metabolism crates and randomly allotted to the 8 diets
      with 10 replicate pigs per diet in a randomized complete block design. Fecal and
      urine samples were collected using the marker-to-marker approach. Results
      indicated that the requirement for STTD Ca to maximize Ca and P retention (g/d)
      was 0.60 and 0.49%, respectively. In conclusion, the STTD Ca requirement by 11-
      to 25-kg pigs to maximize bone ash was 0.48%; however, ADG and G:F declined if
      more than 0.54 or 0.50% STTD Ca, respectively, was fed, and the minimum
      concentration of Ca needed to maximize ADG and G:F could not be determined under
      the conditions of this experiment. Increasing dietary Ca decreased the mRNA
      expression of several genes related to transcellular Ca transport in the jejunum
      and the kidneys.

PMID- 27695787
TI  - Methane emissions changed nonlinearly with graded substitution of alfalfa silage
      with corn silage and corn grain in the diet of sheep and relation with rumen
      fermentation characteristics in vivo and in vitro.
AB  - Feeding grain and corn silage have been proposed as practices to reduce enteric
      methane (CH) emissions per unit of intake from ruminants, but the inclusion level
      required in the diet is normally not specified. The objectives of the current
      study were to determine the CH emission factor (g/kg DMI) of sheep fed alfalfa
      silage substituted with increasing levels of corn silage or corn grain at a fixed
      DMI level (2% of BW) and determine its relationship with rumen fermentation
      characteristics and microbial community composition and with in vitro
      fermentation characteristics of the same diets incubated using a standard
      laboratory method. Romney ewe hoggets (approximately 14 mo old; = 64) were
      randomly allocated to 8 dietary treatments, which included chaffed alfalfa silage
      alone or substituted with either 25, 50, 75 or 100% corn silage or 25, 50 or 65%
      rolled corn grain on a DM basis. After acclimatization to the diet, DMI and CH
      emissions were measured from individual sheep for 2 consecutive days in open
      circuit respiration chambers and a rumen sample was collected at 3 h after
      feeding. The same diets were also incubated in an automated in vitro gas
      production system for 48 h using rumen liquid of fistulated nonlactating dairy
      cows grazing pasture. Increasing the substitution of alfalfa silage with corn
      silage or corn grain in the diet of sheep resulted in a quadratic response ( <
      0.01) in CH emissions per unit of DMI (CH/DMI) with either supplement. For both
      supplements, CH/DMI increased in mixtures of up to 50% supplement inclusion and
      then decreased with greater supplement inclusion, especially with corn grain
      inclusion, but the level did not fall below that for 100% alfalfa silage. The
      ratio of acetate + butyrate to propionate + valerate and the propionate
      proportion alone in rumen liquid were the strongest single predictors for CH/DMI
      in the overall data set and explained 37.1 and 32.5%, respectively, of the
      variation in CH/DMI. Methanogens of (21.1% of total methanogens; = 0.247) and
      (10.7% of total methanogens; = -0.411) clades had weak to moderate correlations
      with in vivo CH/DMI. There was a weak quadratic relationship ( < 0.35) between in
      vivo CH/DMI and the in vitro parameters of gas and CH production and total VFA,
      whereas there was a moderate relationship ( = -0.50) between in vivo CH/estimated
      rumen degradable carbohydrates and in vitro CH/DM. In conclusion, CH/DMI changed
      in a nonlinear fashion with increasing supplement inclusion in the alfalfa forage
      diet when fed at 2% of BW to sheep; however, implications on predicting its
      influence on greenhouse gas emissions per unit of animal product, for whole farm
      emissions in life cycle analysis or total national emissions in the national
      inventories, should be determined.

PMID- 27695788
TI  - Cloning of oligopeptide transport carrier PepT1 and comparative analysis of PepT1
      messenger ribonucleic acid expression in response to dietary nitrogen levels in
      yak () and indigenous cattle () on the Qinghai-Tibetan plateau.
AB  - The gastrointestinal lumen can directly absorb all di- and tripeptide protein
      degradation products, and oligopeptide absorption depends on the specific peptide
      transport carriers, which are located in gastrointestinal epithelial cells on the
      brush border membrane. Yak () use N more efficiently than cattle do, which
      implies that yak have a specific mechanism of nonprotein utilization including a
      peptide absorption mechanism. However, this mechanism has not been clarified. Our
      objective was to explore whether yak possess any adaptive mechanisms of peptide
      absorption to survive in the harsh foraging environment of the Qinghai-Tibetan
      plateau. Twelve castrated males of each of 2 genotypes, yak () and indigenous
      cattle (), were fed diets of various N levels. The yak PepT1 (yPepT1) cDNA was
      cloned in omasum epithelial tissue. Our results showed that the full-length
      yPepT1 cDNA contains 2,805 bp, and a 2,121-bp open reading frame encodes a
      putative protein of 707 AA residues. The yPepT1 AA sequence identified 5 putative
      extracellular N-glycosylation sites (Asn, Asn, Asn, Asn, and Asn), 2 putative
      intracellular protein kinase A sites (Ser and Thr), and 3 intracellular putative
      protein kinase C sites (Ser, Ser, and Ser). The yPepT1 AA sequence was 99, 95,
      86, and 83% identical to PepT1 from cattle (), sheep (), pigs (), and humans (),
      respectively. The relative PepT1 mRNA expression for indigenous cattle was
      greater than yak in the rumen, omasum, duodenum, ileum, and liver ( < 0.001);
      however, it was lower in jejunum tissue ( < 0.01). The relative PepT1 mRNA
      expression in response to increasing dietary N for both genotypes were linear in
      the rumen and jejunum ( < 0.10); quadratic or cubic in the reticulum ( < 0.01);
      linear or quadratic in the duodenum, ileum, and liver ( <= 0.01); and linear,
      quadratic, or cubic in the omasum ( < 0.001). Moreover, there were significant
      interactions between genotype and dietary N in rumen, reticulum, omasum,
      duodenum, jejunum, ileum, and liver tissues. In conclusion, the PepT1 profile and
      expression in gastrointestinal epithelial cells of yak varied from those of
      cattle, implying that yak have evolved a peptide transport mechanism to adapt the
      environment of the Qinghai-Tibetan plateau.

PMID- 27695789
TI  - Subacute ruminal acidosis reduces sperm quality in beef bulls.
AB  - Breeding bulls are commonly fed high-energy diets, which may induce subacute
      ruminal acidosis (SARA). In this experiment, 8 Santa Gertrudis bulls (age 20 +/-
      6 mo) were used to evaluate the extent and duration of effects of SARA on semen
      quality and the associated changes in circulating hormones and metabolites. The
      bulls were relocated and fed in yards with unrestricted access to hay and daily
      individual concentrate feeding for 125 d before SARA challenge. Semen was
      collected and assessed at 14-d intervals before the challenge to ensure
      acclimatization and the attainment of a stable spermiogram. The challenge
      treatments consisted of either a single oral dose of oligofructose (OFF; 6.5 g/kg
      BW) or an equivalent sham dose of water (Control). Locomotion, behavior,
      respiratory rate, and cardiovascular and gastrointestinal function were
      intensively monitored during the 24-h challenge period. Rumen fluid samples were
      retained for VFA, ammonia, and lactate analysis. After the challenge, semen was
      then collected every third day for a period of 7 wk and then once weekly until 12
      wk, with associated blood collection for FSH, testosterone, inhibin, and cortisol
      assay. Percent normal sperm decreased in bulls dosed with OFF after the challenge
      period ( < 0.05) and continued to remain lower on completion of the study at 88 d
      after challenge. There was a corresponding increase in sperm defects commencing
      from 16 d after challenge. These included proximal cytoplasmic droplets ( <
      0.001), distal reflex midpieces ( = 0.01), and vacuole and teratoid heads ( <
      0.001). Changes in semen quality after challenge were associated with lower serum
      testosterone ( < 0.001) and FSH ( < 0.05). Serum cortisol in OFF bulls tended to
      be greater ( = 0.07) at 7 d after challenge. This study shows that SARA challenge
      causes a reduction in sperm quality sufficient to preclude bulls from sale as
      single sire breeding animals 3 mo after the event occurred.

PMID- 27695790
TI  - Heat stress affects the apparent and standardized ileal digestibilities of amino
      acids in growing pigs.
AB  - Heat stress (HS) appears to impair the pig's small intestine digestive and
      absorptive capacities and, therefore, may affect the AA digestibilities. A
      crossover-designed experiment was conducted utilizing two 7-d periods with 8 pigs
      (30.8 kg initial BW) surgically fitted with T-type cannulas at the terminal ileum
      to analyze the effect of HS on both apparent (AID) and standardized (SID) ileal
      digestibility of AA in pigs fed a wheat-soybean meal diet. Subcutaneous skin and
      ileal lumen temperatures were continuously monitored in 15-min intervals during
      the entire experiment. After recovery from surgery, all pigs were adapted to the
      diet and trained to consume the same amount of feed twice a day for 5 d in
      thermal-neutral (TN) conditions (22 degrees C +/- 2 degrees C). Following
      adaptation, pigs were divided into 2 groups (4 pigs each); 1 remained in TN
      conditions, and the other group was exposed to natural HS (24 degrees C to 45
      degrees C) for 7 d (period 1). In period 2, the 2 groups switched environments.
      Ileal digesta were continuously collected for 12 h, starting at 0700 h, on d 6
      and 7 of each period. Chromic oxide was used as an indicator of intestinal
      digesta flow. The subcutaneous and the ileal temperatures were increased between
      1.3 degrees C and 1.6 degrees C in HS compared to TN pigs ( < 0.001). The AID of
      AA (%) for the TN and HS pigs were Arg, 90.6, 88.1; His, 88.7, 85.9; Ile, 84.8,
      83.9; Leu, 86.9, 84.1; Lys, 86.8, 86.2; Met, 89.8, 89.1; Phe, 86.0, 84.8; Thr,
      76.7, 74.3; and Val, 82.8, 81.7, respectively. The SID (%) of AA for the TN and
      HS pigs were Arg, 94.0, 92.0; His, 92.5, 90.2; Ile, 89.5, 88.1; Leu, 90.1, 88.6;
      Lys, 91.0, 90.1; Met, 94.4, 93.6; Phe, 90.4, 88.9; Thr, 86.0, 83.7; and Val,
      88.1, 86.5, respectively. The AID of Arg, His, and Leu was lower ( < 0.01) in HS
      pigs, and the SID of Arg and His was also lower in HS pigs. Neither the AID nor
      the SID of the remaining essential AA was affected by HS. In summary, the
      digestibility of essential AA is differentially affected in pigs exposed to
      natural HS, and thus, special attention should be given to Arg and His when
      formulating diets for growing pigs under HS conditions.

PMID- 27695791
TI  - Genetic variation for farrowing rate in pigs in response to change in photoperiod
      and ambient temperature.
AB  - Seasonal infertility is often observed as anestrus and a lower conception rate
      resulting in a reduced farrowing rate (FR) during late summer and early autumn.
      This is often regarded as an effect of heat stress; however, we observed a
      reduction in the FR of sows even after correcting for ambient temperature in our
      data. Therefore, we added change in photoperiod in the analysis of FR considering
      its effect on sow fertility. Change in photoperiod was modeled using the cosine
      of the day of first insemination within a year. On an average, the FR decreased
      by 2% during early autumn with decreasing daily photoperiod compared with early
      summer with almost no change in daily photoperiod. It declined 0.2% per degree
      Celsius of ambient temperature above 19.2 degrees C. This result is a step
      forward in disentangling the 2 environmental components responsible for seasonal
      infertility. Our next aim was to estimate the magnitude of genetic variation in
      FR in response to change in photoperiod and ambient temperature to explore
      opportunities for selecting pigs to have a constant FR throughout the year. We
      used reaction norm models to estimate additive genetic variation in response to
      change in photoperiod and ambient temperature. The results revealed a larger
      genetic variation at stressful environments when daily photoperiod decreased and
      ambient temperatures increased above 19.2 degrees C compared with neutral
      environments. Genetic correlations between stressful environments and
      nonstressful environments ranged from 0.90 (+/-0.03) to 0.46 (+/-0.13) depending
      on the severity of the stress, indicating changes in expression of FR depending
      on the environment. The genetic correlation between responses of pigs to changes
      in photoperiod and to those in ambient temperature were positive, indicating that
      pigs tolerant to decreasing daily photoperiod are also tolerant to high ambient
      temperatures. Therefore, selection for tolerance to decreasing daily photoperiod
      should also increase tolerance to high ambient temperatures or vice versa.

PMID- 27695792
TI  - Supplementation of organic and inorganic selenium to late gestation and early
      lactation beef cows effect on cow and preweaning calf performance.
AB  - Angus * Simmental cows ( = 48; BW = 595 +/- 17.4 kg, BCS = 5.26 +/- 0.05, and age
      = 2.3 +/- 0.07 yr), pregnant with male fetuses, were used to determine the effect
      of Se source during the last 80 d of gestation and first 108 d of lactation on
      cow and calf performance. At 203 d in gestation, cows were blocked by BW, breed
      composition, age, and calf sire and randomly allotted to organic Se, inorganic
      Se, or no Se treatments. Diets contained corn silage, corn stover, haylage, dried
      distillers' grains with solubles, and minerals and were formulated to contain
      10.4% CP and 0.90 Mcal/kg NEg during gestation and 12.1% CP and 1.01 Mcal/kg NEg
      during lactation. Diets were fed daily as a total mixed ration and none, 3 mg/d
      Se as sodium selenite, or 3 mg/d Se as Sel-Plex were top-dressed daily. At 68 d
      postpartum (DPP), milk production was calculated using the weigh-suckle-weigh
      procedure and a milk sample was collected to determine composition. At 108 DPP,
      cow-calf pairs were commingled until weaning at 210 DPP. Cow BW and BCS ( >=
      0.56) did not differ between treatments at any time point during the study. Milk
      production, milk fat, and total solids ( >= 0.38) did not differ among
      treatments. Milk protein tended to increase in cows fed inorganic Se compared
      with cows fed organic Se ( = 0.07) and milk lactose tended to be greatest in cows
      fed organic Se ( = 0.10). Conception to AI and overall pregnancy rates did not
      differ between treatments ( >= 0.39). Calf weights and ADG did not differ through
      108 DPP ( >= 0.77) or for the preweaning period ( >= 0.33). Plasma Se
      concentration was adequate for all cows and did not differ among treatments for
      cows ( >= 0.37) or calves ( >= 0.90). Liver Se concentrations in cows fed
      inorganic or organic Se were greater than in control cows ( < 0.01). Longissimus
      muscles biopsies taken from progeny at 108 DPP also did not differ between
      treatments ( = 0.45). In conclusion, dietary Se source did not affect cow
      performance, milk production, or reproductive efficiency. Organic Se decreased
      milk protein and increased milk lactose but did not alter preweaning performance
      of progeny from Se-adequate cows.

PMID- 27695793
TI  - Are all piglets born lightweight alike? Morphological measurements as predictors
      of postnatal performance.
AB  - Birth weight (BiW) of pigs is a commonly used predictor of postnatal performance;
      however, it has been suggested that morphological measurements may be more
      reflective of the intrauterine environment and thus better predictors of
      postnatal growth. The aim of this study was to determine 1) whether morphological
      measurements, including ponderal index (PI), body mass index (BMI), and abdominal
      circumference (AC), could be used as predictors of postnatal performance and 2)
      if so, would they be better predictors than BiW and 3) would the same predictors
      apply to pigs of different BiW at different stages of their growth? Morphological
      measurements, BiW, and BW at d 28 and 70 were available for 731 pigs from
      experiments conducted over a 2-yr period. A series of linear models was used to
      determine predictors that affected growth performance from birth to d 28 and from
      d 28 to 70. For both light (LBiW; <=1.25 kg) and normal BiW pigs (NBiW; 1.60 to
      2.00 kg), BiW was not the best predictor of performance ( > 0.05); different
      variables for the growth periods considered applied to pigs with different BiW.
      For LBiW pigs BMI ( < 0.001) and AC ( = 0.0202) were the best predictors for d 1
      to 28, and AC ( = 0.0317) and PI ( = 0.0450) were the best predictors from d 28
      to 70, with pigs with a larger AC and higher PI/BMI more likely to have higher
      ADG pre- or postweaning. In contrast, the best predictor variables for NBiW pigs
      were AC ( = 0.0482) for d 1 to 28 and crown-rump length (CRL; = 0.0138) for d 28
      to 70. Focusing on LBiW pigs with low ADG, BMI was the best predictor ( < 0.05)
      of growth for pre and postweaning, whereas for LBiW pigs with high ADG the best
      predictors were AC ( = 0.00132) from d 1 to 28 and BiW ( = 0.00601) from d 28 to
      70, with increasing BMI, AC, and BiW associated with greater ADG. For NBiW pigs
      with high preweaning ADG, the best predictor consisted solely of AC ( 0.0210),
      but no morphological predictor variables were significant for NBiW pigs with low
      preweaning ADG. For d 28 to 70, the best predictor for NBiW pigs with low ADG was
      CRL ( = 0.0171), but for high ADG no predictor variables were significant. The
      present study showed that the morphology of piglets is more important than BiW
      when predicting the postnatal growth of pigs; however, which measurement is the
      most important depends on both the BiW and stage of growth. For small-sized pigs,
      these morphological measures may be considered as a decision-making tool by
      farmers when trying to identify potential poor performers.

PMID- 27695794
TI  - Effect of diastatic power and processing index on the feed value of barley grain
      for finishing feedlot cattle.
AB  - The objective of this study was to assess the nutritional value of barley grain
      differing in diastatic power (DP; high vs. low; a malt trait) and processing
      index (PI; 75 vs. 85). One hundred sixty Angus * Hereford crossbred yearling
      steers (467 +/- 38 kg; 144 intact and 16 rumen cannulated) were used in a
      complete randomized 2 * 2 factorial experiment. Steers were assigned to 16 pens,
      8 of which were equipped with the GrowSafe system to measure individual feed
      intake. Cannulated steers (2 per pen) were randomly assigned to the 8 GrowSafe
      pens. Diets consisted of high- or low-DP barley grain (80.0% of diet DM)
      processed to an index of either 75 or 85% (PI-75 and PI-85, respectively).
      Ruminal pH in cannulated steers was measured over four 5-d periods using
      indwelling electrodes. Fecal samples were collected every 28 d from the rectum of
      each steer to assess digestibility using AIA as a marker. No differences ( >
      0.10) in rumen pH were observed among cattle as measured by the indwelling pH
      meters. However, lower ( < 0.05) rumen pH was observed for steers fed low- as
      opposed to high-DP barley in rumen samples collected just prior to feeding and
      measured in the laboratory. Intake of DM and OM were not affected ( >= 0.24) by
      DP but were lower ( < 0.01) with more severe processing (PI-75 vs. PI-85). Low-DP
      barley tended to exhibit higher ( = 0.09) total tract DM digestibility than high
      DP barley. Steers fed PI-75 barley also had higher ( = 0.06) G:F and NEg.
      Digestibility of DM, OM, CP, NDF, and starch was higher ( < 0.05) for PI-75
      barley than for PI-85 barley. Low-DP barley increased ( < 0.05) carcass dressing
      percentage by 0.5% compared with high-DP barley, with a lower PI tending to
      increase ( = 0.06) rib eye area. Compared with steers fed high-DP diets, steers
      fed low-DP diets had more ( = 0.01) total (41.7 vs. 19.4%) and severe liver
      abscesses (22.2 vs. 9.7%). Results suggest that although low-DP barley increased
      liver abscesses, differences in DP did not alter digestion or growth performance
      but low-DP barley did improve dressing percentage. Barley with different DP
      responded similarly to processing, with more intensive processing (PI-75) of
      barley improving starch digestion, feed efficiency, and NEg without negatively
      affecting rumen pH.

PMID- 27695796
TI  - Erratum.

PMID- 27695795
TI  - Comparison of energy rationing systems for late gestation ewes: Impacts on ewe
      and lamb performance.
AB  - The objectives of this study were 1) to compare the effects of a ME () or a NE ()
      system for rationing ewes during late gestation on ewe and progeny performance
      and 2) to investigate incremental increases in NE allocation above 100% of
      recommendation during late gestation on ewe and progeny performance. Fifty-two
      twin-bearing ewes ( = 13 per treatment) were rationed to either 100% of
      recommended ME requirements (100% ME) or 100, 110, or 120% of recommended NE
      requirements (100% NE, 110% NE, and 120% NE) from d 112 of gestation to
      parturition. Mean energy intake, measured as ME and NE, from Day 112 of gestation
      to parturition was higher in all NE treatments compared with 100% ME ewes ( =
      0.01). Ewes offered the 3 NE treatments had a higher live weight at parturition
      compared with 100% ME ewes ( = 0.02), with 100% NE and 120% NE ewes still being
      heavier than 100% ME ewes at 35 d postpartum ( = 0.02). Increasing NE allowance
      resulted in a linear decrease in the level of BCS loss prepartum ( = 0.01) and a
      linear increase in the level of BCS loss postpartum ( = 0.01). There was no
      difference observed between any of the treatments in total colostrum produced to
      18 h postpartum ( = 0.29) or in total colostrum intake to 18 h postpartum ( =
      0.27). Increasing maternal NE allowance led to a linear increase in lamb serum
      IgG concentration at 24 h postpartum ( = 0.03). The estimated milk production of
      120% NE ewes tended to be higher than all other treatments at wk 6 of lactation (
      = 0.08). Colostral SFA levels from 100% ME ewes was lower than that of all 3 NE
      treatments ( = 0.01), and unsaturated fatty acid (UFA) levels in colostrum of the
      100% ME ewes were lower than those of the 100% NE ewes ( = 0.01). Cumulative
      levels of milk SFA, UFA, and MUFA did not differ between treatments ( = 0.19).
      Lamb growth rates during the first 5 wk postpartum were unaffected by treatment (
      = 0.18) as were days to slaughter ( = 0.34). It can be concluded that both ME and
      NE systems used in this study are appropriate for formulating ewe diets during
      late gestation. Increasing NE allocation above 100% altered the pattern of body
      reserve mobilization during late gestation and early lactation without observed
      variations in lamb performance during this time.

PMID- 27695797
TI  - Assessing cow-calf welfare. Part 1: Benchmarking beef cow health and behavior,
      handling; and management, facilities, and producer perspectives.
AB  - Assessment programs are one way beef producers communicate information about
      animal welfare to retailers and the public. Programs that monitor cattle through
      the production cycle (e.g., the Global Animal Partnership) or at individual
      stages (e.g., slaughter; the North American Meat Institute) exist, but to date,
      there is no assessment program addressing welfare specifically in the cow-calf
      sector. The objectives of this study were to measure cow-calf health and handling
      welfare outcomes and gather management, facility, and producer perspective
      information to 1) describe current practices and 2) inform assessment design. A
      welfare assessment, designed using features of similar beef and dairy programs,
      was conducted on 30 California ranches that varied in size (mean 1,051 cows [SD
      1,849], range 28 to 10,000 cows) and location within the state. Cattle health and
      behavior and stockperson handling were measured during a routine procedure (e.g.,
      pregnancy checks) on breeding females ( = 3,065). Management and producer
      perspectives were evaluated through an interview, and facility features were
      recorded at the chute and water access points. Cattle health problems were rare
      and seen only on specific ranches (e.g., prevalence of lame cattle: mean 1.3% [SD
      1.5], range 0 to 7.1%). Cattle behavior and stockperson handling varied between
      ranches (e.g., cattle balking: mean 22.0% [SD 21.9], range 1.6 to 78.3%; electric
      prod use: mean 23.5 [SD 21.5], range 0 to 73.0%). Although some management and
      facility characteristics were shared by most (e.g., all ranches castrated bull
      calves; 86% used alleyways with an anti-back gate), other aspects varied (e.g.,
      weaning age: mean 8.2 mo [SD 1.4], range 6 to 11 mo; 43% used shade cover over
      chute). Most producers shared similar perspectives toward their herd health
      management plan, but their responses varied when asked to evaluate an animal's
      pain experience. In terms of assessment design, there were challenges with
      feasibility (e.g., scheduling a ranch visit on a day cattle were processed was
      difficult), validity (e.g., cattle may back up calmly to adjust posture or
      quickly in response to an aggressive handler; without this context, the welfare
      implications of this behavior are unclear), and comparability (e.g., an explicit
      animal observation period needed to be defined to make comparisons across
      ranches). Future assessment programs should consider these qualities when
      selecting measures to evaluate welfare.

PMID- 27695798
TI  - Letter to the Editor and Rebuttal: Protein and amino acid bioavailability
      estimates for canine foods.

PMID- 27695799
TI  - Evaluating dietary adjustment and collection times for total tract digestibility
      of Ca, P, and the essential microminerals with grower swine.
AB  - An experiment was conducted to determine 1) the length of time necessary for
      grower pigs to adjust to a new diet and 2) the consistency in excretion of urine
      and feces in 4 consecutive 5-d collection periods. The total tract excretion and
      digestibility values for Ca, P, and the essential microminerals were evaluated.
      The experiment was conducted in 6 replicates as a randomized complete block
      design. Pigs were fed a pretest diet from 20 to 40 kg BW that met the
      requirements. At 40 kg, 12 barrows were allotted to stainless-steel metabolism
      crates, where they continued being fed the pretest diet for a 7-d period for
      adjustment purposes. Treatment diets were then fed for the following 20-d period
      in four 5-d intervals. Treatment diets were a corn-soybean meal mixture and
      contained either 1) reduced Ca and P levels and no added microminerals (LOW) or
      2) a diet with elevated Ca and P levels and supplemental microminerals that
      exceeded the pig's requirements (HIGH). The study collected urine and feces.
      Markers were added to the ration at the start of each period to distinguish
      between test intervals. Feces and urine were collected daily, frozen, and
      composited for each period. Analysis of diets and excrement was conducted using
      inductively coupled plasma mass spectrometry technology. In all cases, the
      excreted minerals and digestibility values were greater ( < 0.01) for the
      macrominerals when the HIGH diet was fed, whereas the digestibility values for
      the microminerals were often lower when the HIGH diet was fed. The macrominerals
      Ca and P both had consistent urine and fecal values for each of the final 3
      collection periods within diet. The micromineral values were generally consistent
      for each 5-d collection period but varied between periods for several
      microminerals. These results indicate that a 5-d adjustment period was adequate
      for pigs to adjust to the treatment diets. A 5-d collection period was adequate
      for Ca and P, but the micromineral excretion and digestibility values were more
      variable, and a collection period of 10 d might be warranted. The results also
      indicated that the innate microminerals had a higher digestibility and
      bioavailability than thought previously and their digestibility is greater than
      that of inorganic microminerals. Thus, these results indicate that the innate
      microminerals should be an important factor in establishing the micromineral
      requirements for growing pigs.

PMID- 27695800
TI  - Chemical composition, true nutrient digestibility, and true metabolizable energy
      of novel pet food protein sources using the precision-fed cecectomized rooster
      assay.
AB  - A wide variety of animal protein-based ingredients is commonly used in the pet
      food products. The raw ingredients and processing procedures used may greatly
      affect protein quality. Testing the quality of alternative protein sources is
      necessary and contributes to the sustainability of pet foods. The objective of
      this study was to test the chemical composition of 8 protein sources intended for
      use in dog and cat foods (calamari meal, pork peptone, alligator meal, lamb meal,
      venison meal, chicken meal, and 2 duck meals), and evaluate their true nutrient
      digestibility and nitrogen-corrected true ME (TMEn) using the precision-fed
      cecectomized rooster assay. Calamari meal and pork peptone had lower ash (4.4 and
      3.6% of DM, respectively) but greater CP (88.1 and 80.5% of DM, respectively) and
      either greater or similar GE (5.6 and 5.3 kcal/g of DM, respectively) compared
      with alligator, lamb, venison, chicken, and duck meals (11.8 to 24.5% ash, 58.7
      to 65.9% CP, and 4.6 to 5.3 kcal GE/g). Acid-hydrolyzed fat (AHF) was lower in
      calamari meal (8.7% of DM) compared with the other proteins tested (15.5-22.1% of
      DM). True nutrient digestibility was variable among the protein sources (52 to
      79% of DM, 60 to 83% of OM, 78 to 92% of AHF, and 70 to 89% of GE) with pork
      peptone having the highest DM, AHF, and GE digestibility and calamari meal having
      the highest OM digestibility. True indispensable AA digestibility was highest for
      calamari meal, with all AA having a digestibility greater than 90%. Except for
      histidine, all indispensable AA had a digestibility over 85% for pork peptone. In
      contrast, true indispensable AA digestibility was lowest for lamb meal, with
      histidine having digestibility less than 70% and the other entire indispensable
      AA having digestibility between 72 and 88%. The TMEn of calamari meal (4.82
      kcal/g DM and 86.9% of GE) was greater ( < 0.05) than the other protein sources.
      The lamb meal had the lowest TMEn value (3.12 kcal/g DM and 66.9% of GE), with
      others being intermediate (3.46-4.09 kcal/g DM and 71.2-77.9% of GE). This study
      demonstrates the considerable variability that exists not only in the chemical
      composition but also in the true nutrient digestibility among protein sources
      intended for use in dog and cat foods and justifies further in vivo testing of
      novel protein sources.

PMID- 27695801
TI  - Effects of general anesthesia with ketamine in combination with the neuroleptic
      sedatives xylazine or azaperone on plasma metabolites and hormones in pigs.
AB  - Physiological research with swine often includes sedation or general anesthesia
      (GA), which may influence the basal physiological responses of experimental
      animals and may have the potential to confound or interfere with the effects of
      experimental factors of interest. Using 6 adult female pigs, we investigated
      whether selected plasma metabolites and hormones are influenced by GA induced
      with ketamine (K) and 2 neuroleptic sedatives, namely azaperone (A) and xylazine
      (X). Fasted pigs rotationally received either no drug, a single intravenous
      administration of A or X, or A or X combined with ketamine (AK or XK,
      respectively), and plasma concentrations of glucose, lactate, non-esterified
      fatty acids (NEFA), triglycerides (TG), glucagon, insulin, and cortisol were
      determined for a 5-h period following administration. Azaperone and X induced
      deep sedation, whereas AK and XK induced GA. Overall, the average plasma glucose
      concentrations were increased by A and X, with the latter exerting a stronger
      effect that was also associated with hypoinsulinemia ( < 0.05). Time-dependent
      effects indicated a more rapid increase in glucose concentration due to X or XK
      than AK. Plasma NEFA concentrations were elevated by A and AK and to a lesser
      extent by X and XK ( < 0.05). Plasma lactate and TG levels were elevated by A and
      AK and remained unaffected by X or XK. Plasma cortisol concentrations were
      elevated ( < 0.05) by X and XK and even more so with a single administration of A
      ( < 0.05), while the combined effect of A with ketamine resulted in the highest
      cortisol concentrations ( < 0.05). Our data suggest that the effects of azaperone
      are mediated by cortisol but less so for xylazine, which also indicates that
      azaperone elicits a stronger stress response in pigs. Xylazine probably induces
      long-lasting, fasting-state hyperglycemia through the stimulation of hepatic
      glucose production associated with hypoinsulinemia. A discriminant analysis based
      on the variation in all of the measured metabolites and hormones, collectively,
      indicated that ketamine induced no additional effect on the overall physiological
      response patterns than that of the individual sedatives. In conclusion, the
      neuroleptic sedatives azaperone, and to a lesser extent, xylazine, acutely affect
      the metabolism of pigs, so primary metabolic readouts obtained under these drugs
      may be confounded.

PMID- 27695802
TI  - INVITED REVIEW: Inhibitors of myostatin as methods of enhancing muscle growth and
      development.
AB  - With the increasing demand for affordable, high-quality meat, livestock and
      poultry producers must continually find ways to maximize muscle growth in their
      animals without compromising palatability of the meat products. Muscle mass
      relies on myoblast proliferation during prenatal or prehatch stages and fiber
      hypertrophy through protein synthesis and nuclei donation by satellite cells
      after birth or hatch. Therefore, understanding the cellular and molecular
      mechanisms of myogenesis and muscle development is of great interest. Myostatin
      is a well-known negative regulator of muscle growth and development that inhibits
      proliferation and differentiation in myogenic cells as well as protein synthesis
      in existing muscle fibers. In this review, various inhibitors of myostatin
      activity or signaling are examined that may be used in animal agriculture for
      enhancing muscle growth. Myostatin inhibitors are relevant as potential therapies
      for muscle-wasting diseases and muscle weakness in humans and animals. Currently,
      there are no commercial myostatin inhibitors for agriculture or biomedical
      purposes because the safest and most effective option has yet to be identified.
      Further investigation of myostatin inhibitors and administration strategies may
      revolutionize animal production and the medical field.

PMID- 27695803
TI  - Digestibility of energy, amino acids, and phosphorus in a novel source of soy
      protein concentrate and in soybean meal fed to growing pigs.
AB  - Three experiments were conducted to determine standardized ileal digestibility
      (SID) of CP and AA, DE and ME, and apparent total tract digestibility (ATTD) and
      standardized total tract digestibility (STTD) of P in a new source of soy protein
      concentrate (SPC) and in soybean meal (SBM). In Exp. 1, 9 barrows (initial BW:
      13.08 +/- 1.98 kg) were prepared with a T-cannula in the distal ileum and
      allotted to a triplicated 3 * 3 Latin square design with 3 diets and 3 periods. A
      nitrogen-free diet and 2 diets that contained corn starch and SPC or SBM as the
      sole source of CP and AA were formulated. Each period lasted 7 d, and ileal
      digesta were collected on d 6 and 7 of each period. The SID for Ile, Leu, Phe,
      Pro, and Tyr was greater ( < 0.05) in SPC than in SBM, but for CP and all other
      AA, no difference between SPC and SBM was observed. In Exp. 2, 24 barrows
      (initial BW: 13.94 +/- 1.34 kg) were housed individually in metabolism crates and
      randomly allotted to 1 of 3 diets. A corn-based diet (96.9% corn) and 2 diets
      that contained corn and SPC or corn and SBM were formulated. Each diet was fed to
      8 pigs. Feces and urine samples were collected using the marker to marker method
      with 5-d adaptation and 5-d collection periods. The DE and ME in SPC and SBM were
      calculated using the difference procedure. Results indicated that the ATTD of GE
      was lower ( < 0.05) in SBM than in corn and the DE and ME in SPC were greater ( <
      0.01) than in corn and SBM. In Exp. 3, 40 barrows (initial BW: 14.12 +/- 2.08 kg)
      were placed in metabolism crates and allotted to 4 diets in a randomized complete
      block design with 10 pigs per diet. Two diets were based on SPC or SBM as the
      sole source of P. Two additional diets were formulated by adding microbial
      phytase to diets that were otherwise similar to the 2 initial diets. Feces were
      collected for 5 d after a 5-d adaptation period and values for ATTD and STTD of P
      were calculated. No differences were observed in ATTD and STTD of P between SPC
      and SBM, but the ATTD and STTD of P of both SPC and SBM were greater ( < 0.01) if
      microbial phytase was added to the diets. In conclusion, the concentrations of DE
      and ME are greater in SPC than in SBM, but the SID of most AA and the STTD of P
      are not different between SPC and SBM.

PMID- 27695804
TI  - Growth performance, feed digestibility, body composition, and feeding behavior of
      high- and low-residual feed intake fat-tailed lambs under moderate feed
      restriction.
AB  - Two experiments were conducted to evaluate the effect of moderate feed
      restriction on productivity of lambs classified on the basis of phenotypic
      expression of residual feed intake (RFI). In Exp. 1, 58 fat-tailed Kurdi ram
      lambs (32.1 +/- 4.2 kg BW) were individually fed, ad libitum, a pelleted diet
      (35% alfalfa hay and 65% concentrate). Feed intake and ADG were determined for a
      6-wk period and 3 feed efficiency measures including RFI, G:F, and partial
      efficiency of maintenance (PEM) were calculated. The lambs were sorted based on
      RFI and the 16 highest RFI (RFI >= mean + 0.5 SD) and 16 lowest RFI (RFI <= mean 
      0.5 SD) lambs were subjected to body composition (BC) and DM digestibility (DMD)
      analysis. Feeding behavior traits (FB) were also evaluated for 24 h using a
      regular 5-min interval observation method. The high- and low-RFI lambs (14
      lambs/RFI group) so classified in Exp. 1 were used in Exp. 2. Half of the lambs
      in each RFI group were randomly selected to be fed ad libitum or 85% of ad
      libitum (restricted feeding), which resulted in 4 experimental groups: 1) ad
      libitum high-RFI, 2) feed restricted high-RFI, 3) ad libitum low-RFI, and 4) feed
      restricted low-RFI. The lambs were fed the same diet as Exp. 1, and growth
      efficiency during a 6-wk test period as well as BC, DMD, and FB were also
      determined in Exp. 2. In Exp. 1, the low-RFI lambs consumed 14% ( < 0.01) less
      feed than high-RFI lambs. Differences were also observed between high- and low
      RFI groups for G:F ( = 0.01), RFI ( < 0.01), and PEM ( < 0.01) in Exp. 1, but no
      differences were detected between high- and low-RFI lambs for ADG ( = 0.79), DMD
      ( = 0.42), BC ( > 0.72), and FB ( > 0.24). In Exp.2, the restriction feeding
      regime negatively affected ADG ( < 0.01) and G:F ( = 0.02) in low-RFI lambs,
      whereas G:F ( = 0.02) and PEM ( < 0.01) were improved in high-RFI lambs under the
      feed restriction condition. No effects of feed restriction on DMD ( = 0.87) and
      BC ( > 0.05) were observed. The lambs fed at the restricted level of intake
      presented a greater time ( < 0.01) and rate ( = 0.01) of eating than those fed ad
      libitum. Although bunk visits and feeding events were decreased ( < 0.01) with
      feed restriction, no interaction ( > 0.05) was detected between RFI phenotype and
      feeding regime for FB. In summary, feeding high-RFI lambs at 85% of ad libitum
      level improved G:F with no effect on ADG, whereas growth performance was reduced
      by feeding low-RFI lambs at 85% of ad libitum. However, these changes in feed
      efficiency were not related to DMD, BC, or FB.

PMID- 27695805
TI  - Comparison of visual and electronic devices for individual identification of
      dromedary camels under different farming conditions.
AB  - The camel industry uses traditional (i.e., iron brands and ear tags) and modern
      (i.e., microchips) identification (ID) systems without having performance results
      of reference. Previously iron-branded ( = 45; 1 yr) and microchipped ( = 59; 7
      yr) camels showed problems of healing (8.6% of brands) and reading (only 42.9% of
      brands and 69.5% of microchips were readable), which made their use inadvisable.
      With the aim of proposing suitable ID systems for different farming conditions,
      an on-field study was performed using a total of 528 dromedaries at 4 different
      locations (Egypt, = 83; Spain, = 304; Saudi Arabia, = 90; and Tunisia, = 51). The
      ID devices tested were visual (button ear tags, 28.5 mm diameter, = 178; double
      flag ear tags, 50 by 15 mm, = 83; both made of polyurethane) and electronic (ear
      tags, = 90, and rumen boluses, = 555). Electronic ear tags were polyurethane-loop
      type (75 by 9 mm) with a container in which a 22-mm transponder of full-duplex
      technology was lodged. Electronic boluses of 7 types, varying in dimensions (50
      to 76 mm length, 11 to 21 mm width, and 12.7 to 82.1 g weight) and specific
      gravity (SG; 1.49 to 3.86) and each of them containing a 31-mm transponder of
      half-duplex technology, were all administered to the dromedaries at the beginning
      of the study. When a low-SG bolus was lost, a high-SG bolus was readministered.
      Readability rates of each ID system were evaluated during 1 to 3 yr, according to
      device and location, and yearly values were estimated for comparison. On a yearly
      basis, visual ear tag readability was not fully satisfactory; it was lower for
      rectangular ear tags (66.3%) than for button ear tags (80.9%). Yearly readability
      of electronic ear tags was 93.7%. Bolus readability dramatically varied according
      to their SG; the SG < 2.0 boluses were fully lost after 8 mo. In contrast, the SG
      > 3.0 boluses were efficiently retained (99.6 to 100%) at all locations. In
      conclusion, according to the expected long lifespan of camels, low ID
      performances were observed for iron brands, injectable microchips, and ear tags
      (visual and electronic), making their use inadvisable as unique ID systems in
      camels. The high readability of dense electronic boluses recommended their use as
      a permanent ID device of reference in camels.

PMID- 27695806
TI  - Assessing cow-calf welfare. Part 2: Risk factors for beef cow health and behavior
      and stockperson handling.
AB  - Epidemiological studies can be used to identify risk factors for livestock
      welfare concerns but have not been conducted in the cow-calf sector for this
      purpose. The objectives of this study were to investigate the relationships of 1)
      herd-level management, facilities, and producer perspectives with cattle health
      and behavior and stockperson handling and 2) stockperson handling on cattle
      behavior at the individual cow level. Cow ( = 3,065) health and behavior and
      stockperson handling during a routine procedure (e.g., pregnancy checks) were
      observed on 30 California ranches. Management and producer perspectives were
      evaluated using an interview, and handling facility features were recorded at the
      chute. After predictors were screened for univariable associations, multivariable
      models were built for cattle health (i.e., thin body condition, lameness,
      abrasions, hairless patches, swelling, blind eyes, and dirtiness) and behavior
      (i.e., balking, vocalizing, stumbling and falling in the chute and while exiting
      the restraint, and running out of the restraint) and stockperson handling (i.e.,
      electric prod use, moving aid use, tail twisting, and mis-catching cattle). When
      producers empathized more toward an animal's pain experience, there was a lower
      risk of swelling (odds ratio [OR] = 0.7) but a higher risk of lameness (OR =
      1.3), which may indicate a lack of awareness of the latter. Training stockpersons
      using the Beef Quality Assurance program had a protective effect on cow
      cleanliness and mis-catching in the restraint (OR = 0.2 and OR = 0.5,
      respectively). Hydraulic chutes increased the risk of vocalizations (OR = 2.7),
      possibly because these systems can apply greater pressure to the sides of the
      animal than manual restraints. When a moving aid was used to move an individual
      cow, it increased the risk of her balking, but when hands, in particular, were
      used, the risk of balking decreased across the herd (OR = 34.1 and OR = 0.3,
      respectively). Likewise, individual cows were at a greater risk of balking,
      vocalizing, stumbling and falling in the chute, and stumbling and running at exit
      when they were touched with an electric prod (OR = 11.0, OR = 3.3, OR = 1.9, OR =
      2.3, OR = 1.8, and OR = 1.7, respectively). Although the implications of using
      moving aids are unclear, reducing the use of electric prods could improve cattle
      handling. In conclusion, cattle handling was influenced by a number of facility
      and stockperson factors: personnel training, facility design, and electric prod
      use are key areas for future improvements.

PMID- 27695807
TI  - Effects of limonene on ruminal concentrations, fermentation, and lysine
      degradation in cattle.
AB  - Previous in vitro data showed that was inhibited by limonene. We further
      evaluated effects of limonene on growth of in vitro as well as on ruminal
      concentrations of in vivo. With in vitro cultivation in anaerobic brain-heart
      infusion broth, limonene decreased growth of . Thymol also reduced growth of ,
      but it was less effective than limonene. Tylosin effectively reduced growth of in
      vitro. Although the response over fermentation times and concentrations of
      antimicrobials differed somewhat between tylosin and limonene, the 2
      antimicrobial agents yielded similar inhibitory effects on growth of at
      concentrations ranging from 6 to 24 mg/L. The effects of limonene on ruminal
      concentration in vivo were tested in 7 ruminally cannulated heifers (225 kg
      initial BW) used in a 7 * 4 Youden square design. Treatments included: 1)
      control, 2) limonene at 10 mg/kg diet DM, 3) limonene at 20 mg/kg diet DM, 4)
      limonene at 40 mg/kg diet DM, 5) limonene at 80 mg/kg diet DM, 6) CRINA-L (a
      blend of essential oil components) at 180 mg/kg diet DM, and 7) tylosin at 12
      mg/kg diet DM. Each period included 11 d with 10 d washouts between periods.
      Samples of ruminal contents were collected before treatment initiation and after
      4, 7, and 10 d of treatment for measuring by the most probable number method
      using selective culture medium. Limonene linearly decreased ( = 0.03) ruminal
      concentration, with the lowest concentration achieved with 40 mg of limonene/kg
      dietary DM. Limonene tended ( <= 0.07) to linearly reduce ruminal molar
      proportions of propionate and valerate while tending to linearly increase ( <=
      0.10) those of butyrate and 2-methyl butyrate. Limonene did not affect ruminal NH
      concentrations or degradation rates of lysine. Neither CRINA-L ( = 0.52) nor
      tylosin ( = 0.19) affected ruminal concentrations. CRINA-L significantly
      decreased ruminal concentrations of NH and molar proportions of 3-methyl
      butyrate, whereas tylosin significantly decreased molar proportions of propionate
      while increasing those of butyrate and tending to increase those of acetate.
      Limonene supplementation reduced ruminal concentrations of suggesting that it may
      have the potential to reduce the prevalence of liver abscesses, although further
      research is needed to assess the effect of limonene in feedlot cattle.

PMID- 27695808
TI  - Kinetics of phosphorus absorption in ligated small intestinal segments of
      broilers.
AB  - Two experiments were conducted using 22-d-old Arbor Acres male broilers to study
      the kinetics of inorganic P absorption and the effect of P treatment on Type IIb
      sodium-phosphate cotransporter (NaP-IIb) mRNA and protein levels in ligated
      segments from different intestinal regions. In Exp. 1, the P absorption in
      different small intestinal segments at different postperfusion times (0, 2.5, 5,
      10, 20, or 40 min) were compared. In Exp. 2, different small intestinal loops
      were perfused with solutions containing 0, 1.5, 3, 6, 12, 24, or 48 mmol P/L as
      KHPO, and P concentrations in perfusates were determined at 20 min after
      perfusion. The mRNA levels of NaP-IIb in different small intestinal loops and
      protein expression levels in the duodenums from the control group and the 6 or 48
      mmol P/L group were analyzed. The results from Exp. 1 showed that P absorption
      increased in an asymptotic response to postperfusion time within 40 min in all
      the intestinal segments and P absorption was greater ( < 0.04) in the duodenum
      than in the other 2 segments at 20 min after perfusion, indicating that the
      duodenum is the main site of P absorption in the small intestine of chicks. In
      Exp. 2, the kinetic curves showed that P absorption in the duodenum was a
      saturated carrier mediated process and in the jejunum or ileum occurred with a
      nonsaturated diffusion process. In addition, the b mRNA levels were greater ( <
      0.0001) in the duodenum than in the other 2 segments in the 3 groups (0, 6, or 48
      mmol P/L), further indicating that P absorption in the duodenum occurred mainly
      by a saturated carrier mediated process. However, no significant differences ( =
      0.20) in the NaP-IIb protein levels of the duodenum were observed among the 0, 6,
      and 48 mmol P/L groups. In conclusion, this study suggests by our criteria in
      ligated intestinal loops that the duodenum is the main site of P absorption and
      that P absorption may be a saturated carrier mediated process in the duodenum but
      a nonsaturated diffusion process in the jejunum or ileum of broilers.

PMID- 27695809
TI  - BEEF CATTLE NUTRITION SYMPOSIUM: Feeding Holstein steers.

PMID- 27695810
TI  - Effects of dietary copper, zinc, and ractopamine hydrochloride on finishing pig
      growth performance, carcass characteristics, and antimicrobial susceptibility of
      enteric bacteria.
AB  - A total of 480 pigs (PIC 327 * 1050; initially 48.7 +/- 2.3 kg) were used to
      determine the interactive effects of supplemental Cu, Zn, and ractopamine HCl
      (RAC) on finishing pig growth performance, carcass characteristics, and
      antimicrobial susceptibility of enteric bacteria. Treatments were arranged in a 2
      * 2 * 2 factorial with the main effects of added Cu (CuSO; 0 vs. 125 mg/kg Cu),
      Zn (ZnO; 0 vs. 150 mg/kg Zn), and RAC (0 vs. 10 mg/kg during the last 28 d prior
      to marketing). All diets contained 11 mg/kg Cu and 73 mg/kg Zn from the trace
      mineral premix. Pens of pigs were balanced and blocked on initial BW and then
      randomly allotted to 1 of the 4 mineral treatment diets. At 28 d prior to
      marketing, pens within each block and mineral treatment were randomly assigned to
      receive either 0 or 10 mg/kg RAC in addition to the mineral treatment. Adding
      either Cu or Zn alone did not improve ADG or ADFI yet resulted in numerical
      improvements in overall G:F and caloric efficiencies, but improvements were not
      additive (Cu * Zn, = 0.057, = 0.068, and = 0.064 for G:F and caloric efficiency
      on a ME and NE basis, respectively). Ractopamine improved ( < 0.001) overall ADG,
      G:F, and caloric efficiency, thereby increasing final BW by 3% with no change in
      ADFI. Ractopamine also increased ( < 0.001) HCW, percentage carcass yield, G:F,
      loin depth, and percent fat-free lean and decreased ( = 0.014) backfat. Adding Zn
      or Cu alone to diets containing RAC numerically improved percent yield and HCW
      G:F, but this effect was absent when the Cu or Zn was added to the control diet
      or when Cu and Zn were fed in combination in RAC diets (Cu * Zn * RAC, = 0.011
      and = 0.018 for yield and HCW G:F, respectively). Fecal samples were collected on
      d 0 and at the conclusion of the finishing period (d 90) for bacterial isolation
      and antimicrobial susceptibility determinations according to Clinical and
      Laboratory Standards Institute minimal inhibitory concentrations breakpoints.
      spp. and isolates displayed varying levels of resistance to certain antibiotics
      prior to initiation of treatments on d 0. Resistance to most antibiotics
      decreased ( < 0.05) over time or was stable for those that had a low baseline
      percentage of resistance. Neither Zn nor RAC adversely affected antimicrobial
      resistance. However, extended feeding of 125 mg/kg Cu throughout the finishing
      period seems to decrease enterococcal susceptability to tetracycline, tylosin,
      and quinupristin/dalfopristin.

PMID- 27695811
TI  - Technical note: A special apparatus for facilitating the in situ nylon bag
      measurement of the ruminal degradation of feedstuffs in cattle.
AB  - A new apparatus, named Bang-Bang (BB), which can facilitate the in situ nylon bag
      measurement of ruminal degradation in beef cattle, is described. The BB is an
      apparatus specially designed as a replacement of the traditional steel chain or
      flexible plastic tubes for binding the bags used in the in situ nylon bag (ISNB)
      method. The BB apparatus consists of cylindrical pedestals, sealing clips, nylon
      string, and nylon bags. A series of in situ rumen incubations using 3 ruminally
      cannulated beef steers were conducted to compare the BB with the ISNB method by
      measuring rumen DM degradation kinetics of 12 different feedstuffs commonly
      offered to beef cattle in China. Greater ( < 0.01) DM disappearance and less ( <
      0.01) relative SD (%) were observed with the BB than with the ISNB method. In
      addition, effective degradability of DM was highly correlated between the 2
      methods (ISNB = (1.01 +/- 0.04 * BB) - 4.03 +/- 2.12; = 0.99, < 0.001, = 12).
      These results indicate that the BB apparatus can be effectively used to determine
      the rumen degradation properties of feedstuffs with advantages over the
      traditional ISNB technique.

PMID- 27695812
TI  - Differences in body condition of gilts that are maintained from mating to the end
      of gestation affect mammary development.
AB  - The goal of this project was to determine if different body conditions in late
      gestation that are due to varying body conditions at mating affect mammary
      development and mammary gene expression of gilts. Gilts that were fed ad libitum
      in the growing period were selected based on their backfat depths to form 3
      groups at mating, namely, low backfat (LBF; 12-15 mm; = 14), medium backfat (MBF;
      17-19 mm; = 15), and high backfat (HBF; 22-26 mm; = 16). During gestation, LBF,
      MBF, and HBF gilts were fed approximately 1.25, 1.43, and 1.63 times maintenance
      requirements to maintain their differences in body condition. Feed intake was
      increased by 1 kg in the last 10 d of gestation. Backfat depths of gilts were
      ultrasonically measured at mating and on d 30, 50, 70, 100, and 109 of gestation.
      Blood samples were obtained at mating and on d 109 of gestation to measure
      concentrations of IGF-1, glucose, insulin, estradiol, urea, free fatty acids,
      leptin, and adiponectin. Gilts were slaughtered on d 110 of gestation to collect
      mammary glands for compositional analyses. Mammary extraparenchymal tissue weight
      was lesser in LBF and MBF gilts than in HBF gilts (1,259.3, 1,402.7, and 1,951.5
      +/- 70.4 g, respectively; < 0.01). The weight of parenchymal tissue was not
      affected by treatment ( > 0.10), but its composition was altered. Concentrations
      of DNA and RNA decreased as backfat depth increased ( < 0.05), whereas percent
      fat and DM increased ( < 0.05). Circulating concentrations of leptin tended to be
      lower at mating ( < 0.10) and were lower on d 109 of gestation ( < 0.05) in LBF
      gilts than in HBF gilts. On d 109 of gestation, concentrations of insulin ( <
      0.01) and IGF-1 ( < 0.05) were lower in LBF and MBF gilts than in HBF gilts,
      whereas those of urea were greater ( < 0.05). The mRNA abundance in parenchymal
      tissue for all genes studied was not affected by treatments ( > 0.10) with the
      exception of , which had a greater expression level in LBF gilts than in MFB or
      HBF gilts ( < 0.05). Percent of Ki-67-positive cells, used to assess mammary cell
      proliferation rate, was greater in HBF gilts than in LBF gilts ( < 0.05). When
      differences in body conditions of gilts that were present at mating were
      maintained throughout gestation, it had an impact on mammary development.
      Extraparenchymal tissue mass was affected and, more importantly, composition of
      parenchymal tissue was altered, indicating a beneficial effect of gilts being in
      the thinner treatment groups at mating.

PMID- 27695813
TI  - Dynamics of nitrogen retention in gestating gilts at two feeding levels.
AB  - Whole-body protein deposition (Pd) is a main determinant of AA requirements of
      gestating gilts; however, data on the dynamics of Pd is limited. The main
      objective of this study was to measure whole-body Pd (pregnancy-associated and
      maternal) during gestation in gilts at 2 feeding levels. Changes in BW and
      backfat (BF) throughout gestation and subsequent lactation performance were also
      evaluated. We hypothesized that the effect of feed intake on maternal Pd
      decreases toward the end of gestation due to increased fetal nutrient demands.
      Fifty-one pregnant Yorkshire gilts (initial BW and BF at d 28 +/- 0.5 of
      gestation were 168.6 +/- 2.2 kg and 16.9 +/- 0.8 mm, respectively) were used.
      Gilts were assigned to 1 of 2 feeding levels (high feeding level and low feeding
      level; 2.54 and 1.87 kg/d, respectively) of the same diet (3.30 Mcal ME/kg, 17.8%
      CP, 0.82% standard ileal digestible Lys) from d 33 to 112 +/- 0.5 of gestation.
      Nitrogen balance observations (based on total urine collection with urinary
      catheters and determination of fecal N digestibility using an indigestible
      marker) were made at 5 distinct time periods, each 4 d in length, starting at d
      38, 52, 66, 87, and 108 +/- 0.5 of gestation. Pregnancy-associated Pd (fetus,
      mammary gland, uterus, and placenta and fluids) was calculated for each gilt and
      N balance period using the gestating sow model, based on actual litter size
      (including stillborns) and mean piglet birth weight. Maternal Pd was calculated
      as the difference between whole-body Pd and pregnancy-associated Pd. Across all N
      balance periods, whole-body and maternal Pd were consistently 40.1 +/- 5.2 g/d
      greater ( < 0.001) for the high feeding level compared with the low feeding
      level. At both feeding levels, whole-body Pd increased (linear and quadratic, <
      0.020) with day of gestation and maternal Pd decreased (cubic, < 0.010) with day
      of gestation. During lactation, maternal voluntary feed intake and litter
      performance were not affected by gestation feeding level. Gilts on the high
      feeding level lost more BW and BF during lactation ( <= 0.030). In summary, the
      effect of feeding level on whole-body and maternal Pd was constant throughout
      gestation. However, the gradual decline in maternal Pd with day of gestation is
      in contrast to that reported by the and has important implications for the
      factorial estimation of AA requirements of gestating gilts toward the end of
      gestation.

PMID- 27695814
TI  - Production, Management, and Environment Symposium: Environmental footprint of
      livestock production - Greenhouse gas emissions and climate change.

PMID- 27695815
TI  - Analytical methods for quantifying greenhouse gas flux in animal production
      systems.
AB  - Given increased interest by all stakeholders to better understand the
      contribution of animal agriculture to climate change, it is important that
      appropriate methodologies be used when measuring greenhouse gas (GHG) emissions
      from animal agriculture. Similarly, a fundamental understanding of the
      differences between methods is necessary to appropriately compare data collected
      using different approaches and design meaningful experiments. Sources of carbon
      dioxide, methane, and nitrous oxide emissions in animal production systems
      includes the animals, feed storage areas, manure deposition and storage areas,
      and feed and forage production fields. These 3 gases make up the primary GHG
      emissions from animal feeding operations. Each of the different GHG may be more
      or less prominent from each emitting source. Similarly, the species dictates the
      importance of methane emissions from the animals themselves. Measures of GHG flux
      from animals are often made using respiration chambers, head boxes, tracer gas
      techniques, or in vitro gas production techniques. In some cases, a combination
      of techniques are used (i.e., head boxes in combination with tracer gas). The
      prominent methods for measuring GHG emissions from housing include the use of
      tracer gas techniques or direct or indirect ventilation measures coupled with
      concentration measures of gases of interest. Methods for collecting and measuring
      GHG emissions from manure storage and/or production lots include the use of
      downwind measures, often using photoacoustic or open path Fourier transform
      infrared spectroscopy, combined with modeling techniques or the use of static
      chambers or flux hood methods. Similar methods can be deployed for determining
      GHG emissions from fields. Each method identified has its own benefits and
      challenges to use for the stated application. Considerations for use include
      intended goal, equipment investment and maintenance, frequency and duration of
      sampling needed to achieve desired representativeness of emissions over time,
      accuracy and precision of the method, and environmental influences on the method.
      In the absence of a perfect method for all situations, full knowledge of the
      advantages and disadvantages of each method is extremely important during the
      development of the experimental design and interpretation of results. The
      selection of the suitable technique depends on the animal production system,
      resource availability, and objective for measurements.

PMID- 27695816
TI  - Dexamethasone treatment differentially alters viral shedding and the antibody and
      acute phase protein response after multivalent respiratory vaccination in beef
      steers.
AB  - Our objective was to examine immunosuppression induced by dexamethasone (DEX)
      administration in cattle on immunological responses to a multivalent respiratory
      vaccine containing replicating and nonreplicating agents. Steers ( = 32; 209 +/-
      8 kg) seronegative to infectious bovine rhinotracheitis virus (IBRV), bovine
      viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), and
      parainfluenza-3 virus (PI3V) were stratified by BW and randomly assigned to 1 of
      3 treatments: 1) acute immunosuppression (ACU; 0.5 mg/kg BW DEX intravenously at
      1000 h only on d 0), 2) chronic immunosuppression (CHR; 0.5 mg/kg BW DEX
      intravenously at 1000 h on d -3 to 0), or 3) a control (CON; no DEX). On d -4,
      steers were fitted with intravenous catheters in the jugular vein and placed into
      individual stanchions. At 1200 h on d 0, steers were administered a respiratory
      vaccine containing modified-live virus (MLV) isolates of IBRV, BVDV, BRSV, and
      PI3V and a (MH) toxoid. On d 4, cattle were transported (177 km) and housed in an
      isolated outdoor pen. Serum was harvested on d 0, 7, 14, 21, 28, 35, 42, and 56
      to determine IBRV-, BVDV-, BRSV-, and PI3V-specific antibody titers and MH whole
      cell and leukotoxin antibody concentrations. Sera from d -2, 0, 1, 3, 7, and 14
      were used to quantify haptoglobin (Hp) concentration and ceruloplasmin (Cp)
      activity. Nasal swab specimens were collected on d 0, 3, and 14 to determine the
      presence of IBRV, BVDV, BRSV, and PI3V via PCR analysis. There was a treatment *
      day interaction ( < 0.01) such that CHR steers had a greater ( <= 0.07) BVDV
      antibody titer on d 14, 21, and 28. Moreover, IBRV-specific antibodies increased
      beginning on d 14 for CHR and on d 28 for ACU and remained greater through d 56
      compared with CON ( <= 0.03). Conversely, serum MH whole cell antibody
      concentration was least ( <= 0.06) for CHR from d 7 to 28 and greatest for CON (
      <= 0.04) on d 56. Treatment altered Hp such that CON exhibited a greater ( <
      0.01) Hp concentration than CHR but was not different from ACU ( = 0.16). On d 3,
      Cp was greatest for CON, intermediate for ACU, and least for CHR (treatment *
      day; <= 0.01). The prevalence of IBRV and BVDV in nasal swabs on d 14 was 67 and
      56%, respectively, for CHR; 10 and 10%, respectively, for CON; and 9 and 0%,
      respectively, for ACU ( <= 0.006). Results suggest that CHR allowed increased
      replication of MLV vaccine agents. Conversely, DEX-induced immunosuppression
      blunted the acute phase protein and antibody response against the nonreplicating
      MH toxoid.

PMID- 27695817
TI  - Impacts of supplemental arginine on the reproductive performance of fall lambing
      ewes.
AB  - In sheep, embryonic and fetal death during pregnancy can account for 25% to 50%
      of the total number of corpora lutea (and thus potential embryos). The objective
      of this study was to determine the effects of injectable and oral Arg
      supplementation provided for 14 d postbreeding on the reproductive performance of
      naturally stimulated fall lambing ewes. Rambouillet ewes ( = 210) were exposed to
      rams equipped with marking harnesses to induce cyclicity in April 2012. Upon
      estrus detection (d 0) ewes were randomly assigned, in a completely random
      design, to 1 of 6 treatments for a 14-d treatment period: injectable saline (CON;
      = 25), injectable Ala (IVALA; = 20), injectable Arg (IVARG; = 23), oral rumen
      protected Arg (RPARG; = 20), oral fish meal (FM; = 24), or oral soybean meal
      (SBM; = 23). Daily treatments, except CON, IVALA, and SBM, were formulated to
      provide supplemental Arg at 30 mg.kg BW.d and were provided at 0800 h daily. Ewes
      receiving injectable treatments were provided 454 g corn/d postinjection, whereas
      ewes receiving oral supplements were provided a ground ration of their respective
      treatments with corn individually at 0800 h daily. Plasma and serum samples were
      collected on d 0, 2, 4, 6, 8, 10, 12, and 14 from 12 ewes per treatment to
      evaluate plasma progesterone and serum AA concentrations. At lambing, birth
      weight, birth type, and sex were recorded. Weaning weights were recorded when the
      average age of lambs was 85 d. No differences ( >= 0.39) were detected for
      pregnancy, prolificacy, and lambing rates or lamb birth weights among treatments.
      However, litter weaning weight tended to be greater ( = 0.06) and weaning rates
      were greater ( = 0.05) in Arg-injected ewes (1.09, 0.95, 1.29, 0.72, 1.00, and
      0.86, respectively). Plasma progesterone and serum Arg concentrations showed a
      treatment and day effect ( < 0.001), but no treatment * day interaction ( >=
      0.99) was observed. In contrast to previous research, supplemental Arg during the
      first 14 d of pregnancy did not improve pregnancy or lambing rates; however,
      IVARG did positively impact weaning rates.

PMID- 27695818
TI  - Nobel Laureates Pick Food Fight With GMO Foes.

PMID- 27695819
TI  - Explanation of Errors in Abstract and Supplement and in the Reporting of
      Analyses.

PMID- 27695820
TI  - Comparing Non-Vitamin K Oral Anticoagulants: Where We Are Now.

PMID- 27695821
TI  - Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated
      With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation.
AB  - Importance: Dabigatran and rivaroxaban are non-vitamin K oral anticoagulants
      approved for stroke prevention in patients with nonvalvular atrial fibrillation
      (AF). There are no randomized head-to-head comparisons of these drugs for stroke,
      bleeding, or mortality outcomes. Objective: To compare risks of thromboembolic
      stroke, intracranial hemorrhage (ICH), major extracranial bleeding including
      major gastrointestinal bleeding, and mortality in patients with nonvalvular AF
      who initiated dabigatran or rivaroxaban treatment for stroke prevention. Design,
      Setting, and Participants: Retrospective new-user cohort study of 118 891
      patients with nonvalvular AF who were 65 years or older, enrolled in fee-for
      service Medicare, and who initiated treatment with dabigatran or rivaroxaban from
      November 4, 2011, through June 30, 2014. Differences in baseline characteristics
      were adjusted using stabilized inverse probability of treatment weights based on
      propensity scores. The data analysis was performed from May 7, 2015, through June
      30, 2016. Exposures: Dabigatran, 150 mg, twice daily; rivaroxaban, 20 mg, once
      daily. Main Outcomes and Measures: Adjusted hazard ratios (HRs) for the primary
      outcomes of thromboembolic stroke, ICH, major extracranial bleeding including
      major gastrointestinal bleeding, and mortality, with dabigatran as reference.
      Adjusted incidence rate differences (AIRDs) were also estimated. Results: A total
      of 52 240 dabigatran-treated and 66 651 rivaroxaban-treated patients (47% female)
      contributed 15 524 and 20 199 person-years of on-treatment follow-up,
      respectively, during which 2537 primary outcome events occurred. Rivaroxaban use
      was associated with a statistically nonsignificant reduction in thromboembolic
      stroke (HR, 0.81; 95% CI, 0.65-1.01; P = .07; AIRD = 1.8 fewer cases/1000 person
      years), statistically significant increases in ICH (HR, 1.65; 95% CI, 1.20-2.26;
      P = .002; AIRD = 2.3 excess cases/1000 person-years) and major extracranial
      bleeding (HR, 1.48; 95% CI, 1.32-1.67; P < .001; AIRD = 13.0 excess cases/1000
      person-years), including major gastrointestinal bleeding (HR, 1.40; 95% CI, 1.23
      1.59; P < .001; AIRD = 9.4 excess cases/1000 person-years), and with a
      statistically nonsignificant increase in mortality (HR, 1.15; 95% CI, 1.00-1.32;
      P = .051; AIRD = 3.1 excess cases/1000 person-years). In patients 75 years or
      older or with CHADS2 score greater than 2, rivaroxaban use was associated with
      significantly increased mortality compared with dabigatran use. The excess rate
      of ICH with rivaroxaban use exceeded its reduced rate of thromboembolic stroke.
      Conclusions and Relevance: Treatment with rivaroxaban 20 mg once daily was
      associated with statistically significant increases in ICH and major extracranial
      bleeding, including major gastrointestinal bleeding, compared with dabigatran 150
      mg twice daily.

PMID- 27695822
TI  - Alternative Strategies to Inpatient Hospitalization for Acute Medical Conditions:
      A Systematic Review.
AB  - Importance: Determining innovative approaches that better align health needs to
      the appropriate setting of care remains a key priority for the transformation of
      US health care; however, to our knowledge, no comprehensive assessment exists of
      alternative management strategies to hospital admission for acute medical
      conditions. Objective: To examine the effectiveness, safety, and cost of managing
      acute medical conditions in settings outside of a hospital inpatient unit.
      Evidence Review: MEDLINE, Scopus, CINAHL, and the Cochrane Database of Systematic
      Reviews (January 1995 to February 2016) were searched for English-language
      systematic reviews that evaluated alternative management strategies to hospital
      admission. Two investigators extracted data independently on trial design,
      eligibility criteria, clinical outcomes, patient experience, and health care
      costs. The quality of each review was assessed using the revised AMSTAR tool (R
      AMSTAR) and the strength of evidence from primary studies was graded according to
      the Oxford Centre for Evidence-Based Medicine. Findings: Twenty-five systematic
      reviews (representing 123 primary studies) met inclusion criteria. For outpatient
      management strategies, several acute medical conditions had no significant
      difference in mortality, disease-specific outcomes, or patient satisfaction
      compared with inpatient admission. For quick diagnostic units, the evidence was
      more limited but did demonstrate low mortality rates and high patient
      satisfaction. For hospital-at-home, a variety of acute medical conditions had
      mortality rates, disease-specific outcomes, and patient and caregiver
      satisfaction that were either improved or no different compared with inpatient
      admission. For observation units, several acute medical conditions were found to
      have no difference in mortality, a decreased length of stay, and improved patient
      satisfaction compared to inpatient admission; results for some conditions were
      more limited. Across all alternative management strategies, cost data were
      heterogeneous but showed near-universal savings when assessed. Conclusions and
      Relevance: For low-risk patients with a range of acute medical conditions,
      evidence suggests that alternative management strategies to inpatient care can
      achieve comparable clinical outcomes and patient satisfaction at lower costs.
      Further study and application of such opportunities for health system redesign is
      warranted.

PMID- 27695823
TI  - Association of Stimulant Medication Use With Bone Mass in Children and
      Adolescents With Attention-Deficit/Hyperactivity Disorder.
AB  - Importance: Murine studies reveal that sympathetic nervous system activation
      leads to decreased bone mass. Stimulant medications used to treat attention
      deficit/hyperactivity disorder (ADHD) increase sympathetic tone and may affect
      bone remodeling. Because bone mass accrual is completed by young adulthood,
      assessing stimulant effects on bone density in growing children is of critical
      importance. Objective: To investigate associations between stimulant use and bone
      mass in children and adolescents. Design, Setting, and Participants: This cross
      sectional analysis used data collected from January 1, 2005, to December 31,
      2010, from the National Health and Nutrition Examination Survey (NHANES)
      database. NHANES is a series of cross-sectional, nationally representative health
      and nutrition surveys of the US population. All children, adolescents, and young
      adults aged 8 to 20 years with dual-energy x-ray absorptiometry (DXA),
      anthropometric, demographic, and prescription medication use data were eligible
      for participation. Of the 6489 respondents included in the multivariable linear
      regression analysis, 159 were stimulant users and 6330 were nonusers. Data were
      analyzed from October 8, 2015, to December 31, 2016. Exposures: Stimulant use,
      determined by questionnaires administered via interview. Main Outcomes and
      Measures: The association between stimulant use and total femur, femoral neck,
      and lumbar spine bone mineral content (BMC) and bone mineral density (BMD) was
      assessed using DXA. Results: Study participants included 6489 NHANES participants
      with a mean (SD) age of 13.6 (3.6) years. Stimulant use was associated with lower
      bone mass after adjustment for covariates. Mean lumbar spine BMC was
      significantly lower in stimulant users vs nonusers (12.76 g; 95% CI, 12.28-13.27
      g vs 13.38 g; 95% CI, 13.26-13.51 g; P = .02), as was mean lumbar spine BMD (0.90
      g/cm2; 95% CI, 0.87-0.94 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .03)
      and mean femoral neck BMC (4.34 g; 95% CI, 4.13-4.57 g vs 4.59 g; 95% CI, 4.56
      4.62 g; P = .03). Mean BMD of the femoral neck (0.88 g/cm2; 95% CI, 0.84-0.91
      g/cm2 vs 0.91 g/cm2; 95% CI, 0.90-0.91 g/cm2; P = .08) and total femur (0.94
      g/cm2; 95% CI, 0.90-0.99 g/cm2 vs 0.99 g/cm2; 95% CI, 0.98-0.99 g/cm2; P = .05)
      were also lower in stimulant users vs nonusers. Participants treated with
      stimulants for 3 months or longer had significantly lower lumbar spine BMD (0.89
      g/cm2; 95% CI, 0.85-0.93 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .02)
      and BMC (12.71 g; 95% CI, 12.14-13.32 g vs 13.38 g; 95% CI, 13.25-13.51 g; P =
      .03) and femoral neck BMD (0.87 g/cm2; 95% CI, 0.74-0.83 g/cm2 vs 0.91 g/cm2; 95%
      CI, 0.83-0.84 g/cm2; P = .048) than nonusers. Conclusions and Relevance: Children
      and adolescents reporting stimulant use had lower DXA measurements of the lumbar
      spine and femur compared with nonusers. These findings support the need for
      future prospective studies to examine the effects of stimulant use on bone mass
      in children.

PMID- 27695825
TI  - Prediabetes Risk in Adult Americans According to a Risk Test.

PMID- 27695826
TI  - Subclinical Hypothyroidism in Elderly Individuals-Overdiagnosis and
      Overtreatment?: A Teachable Moment.

PMID- 27695824
TI  - Effect of Hydrocortisone on Development of Shock Among Patients With Severe
      Sepsis: The HYPRESS Randomized Clinical Trial.
AB  - Importance: Adjunctive hydrocortisone therapy is suggested by the Surviving
      Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone
      in patients with severe sepsis without shock remains controversial. Objective: To
      determine whether hydrocortisone therapy in patients with severe sepsis prevents
      the development of septic shock. Design, Setting, and Participants: Double-blind,
      randomized clinical trial conducted from January 13, 2009, to August 27, 2013,
      with a follow-up of 180 days until February 23, 2014. The trial was performed in
      34 intermediate or intensive care units of university and community hospitals in
      Germany, and it included 380 adult patients with severe sepsis who were not in
      septic shock. Interventions: Patients were randomly allocated 1:1 either to
      receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by
      dose tapering until day 11 (n = 190) or to receive placebo (n = 190). Main
      Outcomes and Measures: The primary outcome was development of septic shock within
      14 days. Secondary outcomes were time until septic shock, mortality in the
      intensive care unit or hospital, survival up to 180 days, and assessment of
      secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood
      glucose level >150 mg/dL [to convert to millimoles per liter, multiply by
      0.0555]). Results: The intention-to-treat population consisted of 353 patients
      (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of
      170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%)
      in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No
      significant differences were observed between the hydrocortisone and placebo
      groups for time until septic shock; mortality in the intensive care unit or in
      the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170
      patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86),
      90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference,
      3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%]
      vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to
      13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had
      secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle
      weakness, and 90.9% vs 81.5% had hyperglycemia. Conclusions and Relevance: Among
      adults with severe sepsis not in septic shock, use of hydrocortisone compared
      with placebo did not reduce the risk of septic shock within 14 days. These
      findings do not support the use of hydrocortisone in these patients. Trial
      Registration: clinicaltrials.gov Identifier: NCT00670254.

PMID- 27695827
TI  - The Future of High-Quality Care Depends on Better Assessment of Physician
      Performance.

PMID- 27695828
TI  - Error in Acknowledgments.

PMID- 27695830
TI  - Typographical Error in Methods Section.

PMID- 27695829
TI  - Missing Reference Citation.

PMID- 27695832
TI  - East River Reflections.

PMID- 27695833
TI  - A Chance of Showers.

PMID- 27695834
TI  - Effect of Detecting and Isolating Asymptomatic Clostridium difficile Carriers.

PMID- 27695835
TI  - Prescription Trends-Brand-name Drugs vs Generic.

PMID- 27695836
TI  - Patient Experience and Health Care Quality.

PMID- 27695837
TI  - American Society of Anesthesiologist Classification-Higher Incentives for Higher
      Scores.

PMID- 27695838
TI  - American Society of Anesthesiologist Classification-Higher Incentives for Higher
      Scores.

PMID- 27695839
TI  - Payments to Physicians, Prescribing Rates, and More Appropriate Conclusions.

PMID- 27695840
TI  - Payments to Physicians, Prescribing Rates, and More Appropriate Conclusions.

PMID- 27695841
TI  - Effect Of Detecting and Isolating Asymptomatic Clostridium difficile Carriers
      Reply.

PMID- 27695842
TI  - Prescription Trends-Brand-Name Drugs vs Generic-Reply.

PMID- 27695843
TI  - Patient Experience and Health Care Quality-Reply.

PMID- 27695844
TI  - American Society of Anesthesiologist Classification-Higher Incentives for Higher
      Scores-Reply.

PMID- 27695845
TI  - Payments to Physicians, Prescribing Rates, and More Appropriate Conclusions
      Reply.

PMID- 27695847
TI  - Zika Virus-A Public Health Emergency of International Concern.

PMID- 27695848
TI  - Errors in Abstract and Supplement and in Reporting of Analyses.

PMID- 27695849
TI  - Measles and Measles Vaccination: A Review.
AB  - Importance: Measles is a highly communicable viral infection with serious
      complications. There have been continued outbreaks of measles in countries in
      which measles is considered to be eliminated, such as the United States and the
      Netherlands, and measles remains endemic in some countries. Health care
      professionals play an important role in diagnosing and managing acute cases of
      measles, preventing spread during outbreaks, and vaccination uptake. Objective:
      To provide an overview of measles and vaccination for health care professionals.
      Evidence Review: MEDLINE and PubMed were searched from January 1, 1980, to April
      30, 2016, in addition to the data repositories of the Centers for Disease Control
      and Prevention and World Health Organization. Findings: Seven systematic reviews,
      15 reviews, 15 observational studies, 1 qualitative study, 5 epidemiologic
      reports, and 2 books were included, in addition to World Health Organization and
      Centers for Disease Control and Prevention data, position papers, and statements.
      Transmission of measles is dependent on person-to-person spread through
      respiratory droplets or direct contact. Diagnosis is based on recognizing the
      clinical picture and can be confirmed with results of laboratory testing, such as
      serologic tests or polymerase chain reaction. Measles infection leads to immune
      suppression for weeks to months. Complications of measles are of high frequency
      and severity. There is no specific antiviral treatment for measles; treatment
      with vitamin A is recommended for younger children to decrease mortality from
      measles. Vaccination against measles is effective, cost-effective, and safe.
      There is no link between the measles vaccination and autism. Measles can be
      eliminated from a population; this outcome requires coverage with 2 doses of
      vaccine at rates of 93% to 95% of the population. Countries with high rates of
      measles vaccination experience outbreaks by virtue of imported cases causing
      transmission through susceptible groups of individuals who are not immune to the
      measles virus. Endemic transmission can be reestablished if rates of vaccination
      fall below the elimination threshold. Conclusions and Relevance: Measles remains
      of high clinical importance. Health care professionals should be able to diagnose
      and manage an acute case and assist in prevention of the spread of measles during
      an outbreak. Health care professionals also play an important role in uptake of
      measles vaccination through establishing trusting relationships with parents,
      offering vaccination at indicated times, and engaging parents in discussion on
      facts and concerns about vaccination.

PMID- 27695850
TI  - Evaluating Glucocorticoids for Sepsis: Time to Change Course.

PMID- 27695851
TI  - Effects of ParentCorps in Prekindergarten on Child Mental Health and Academic
      Performance: Follow-up of a Randomized Clinical Trial Through 8 Years of Age.
AB  - Importance: Low-income minority children living in urban neighborhoods are at
      high risk for mental health problems and underachievement. ParentCorps, a family
      centered, school-based intervention in prekindergarten, improves parenting and
      school readiness (ie, self-regulation and preacademic skills) in 2 randomized
      clinical trials. The longer-term effect on child mental health and academic
      performance is not known. Objective: To examine whether ParentCorps delivered as
      an enhancement to prekindergarten programs in high-poverty urban schools leads to
      fewer mental health problems and increased academic performance in the early
      elementary school years. Design, Setting, and Participants: This is a 3-year
      follow-up study of a cluster randomized clinical trial of ParentCorps in public
      schools with prekindergarten programs in New York City. Ten elementary schools
      serving a primarily low-income, black student population were randomized in 2005,
      and 4 consecutive cohorts of prekindergarten students were enrolled from
      September 12, 2005, through December 31, 2008. We report follow-up for the 3
      cohorts enrolled after the initial year of implementation. Data analysis was
      performed from September 1, 2014, to December 31, 2015. Interventions:
      ParentCorps included professional development for prekindergarten and
      kindergarten teachers and a program for parents and prekindergarten students (13
      two-hour group sessions delivered after school by teachers and mental health
      professionals). Main Outcomes and Measures: Annual teacher ratings of mental
      health problems and academic performance and standardized tests of academic
      achievement in kindergarten and second grade by testers masked to the
      intervention or control group randomization. Results: A total of 1050 children (4
      years old; 518 boys [49.3%] and 532 girls [50.7%]) in 99 prekindergarten
      classrooms participated in the trial (88.1% of the prekindergarten population),
      with 792 students enrolled from 2006 to 2008. Most families in the follow-up
      study (421 [69.6%]) were low income; 680 (85.9%) identified as non-Latino black,
      78 (9.8%) as Latino, and 34 (4.3%) as other. Relative to their peers in
      prekindergarten programs, children in ParentCorps-enhanced prekindergarten
      programs had lower levels of mental health problems (Cohen d = 0.44; 95% CI, 0.08
      0.81) and higher teacher-rated academic performance (Cohen d = 0.21; 95% CI, 0.02
      0.39) in second grade. Conclusions and Relevance: Intervention in prekindergarten
      led to better mental health and academic performance 3 years later. Family
      centered early intervention has the potential to prevent problems and reduce
      disparities for low-income minority children. Trial Registration:
      clinicaltrials.gov Identifier: NCT01670227.

PMID- 27695852
TI  - Changes in Characteristics and Time to Recognition of Medical Scientists Awarded
      a Nobel Prize.

PMID- 27695853
TI  - Estimating 1-Year Mortality for High-Risk Primary Care Patients Using the
      "Surprise" Question.

PMID- 27695854
TI  - The Medicalization of Common Conditions.

PMID- 27695856
TI  - Early Education Programs for Low-Income Children: The Time for Dissemination Has
      Come.

PMID- 27695858
TI  - Preventing Adolescent Suicide.

PMID- 27695855
TI  - Congenital Zika Virus Infection: Beyond Neonatal Microcephaly.
AB  - Importance: Recent studies have reported an increase in the number of fetuses and
      neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV)
      during pregnancy. To our knowledge, most reports to date have focused on select
      aspects of the maternal or fetal infection and fetal effects. Objective: To
      describe the prenatal evolution and perinatal outcomes of 11 neonates who had
      developmental abnormalities and neurological damage associated with ZIKV
      infection in Brazil. Design, Setting, and Participants: We observed 11 infants
      with congenital ZIKV infection from gestation to 6 months in the state of
      Paraiba, Brazil. Ten of 11 women included in this study presented with symptoms
      of ZIKV infection during the first half of pregnancy, and all 11 had laboratory
      evidence of the infection in several tissues by serology or polymerase chain
      reaction. Brain damage was confirmed through intrauterine ultrasonography and was
      complemented by magnetic resonance imaging. Histopathological analysis was
      performed on the placenta and brain tissue from infants who died. The ZIKV genome
      was investigated in several tissues and sequenced for further phylogenetic
      analysis. Main Outcomes and Measures: Description of the major lesions caused by
      ZIKV congenital infection. Results: Of the 11 infants, 7 (63.6%) were female, and
      the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates
      died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic
      perimeter at birth was 31 (3) cm, a value lower than the limit to consider a
      microcephaly case. In all patients, neurological impairments were identified,
      including microcephaly, a reduction in cerebral volume, ventriculomegaly,
      cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia
      deformation sequence (ie, arthrogryposis). Results of limited testing for other
      causes of microcephaly, such as genetic disorders and viral and bacterial
      infections, were negative, and the ZIKV genome was found in both maternal and
      neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain).
      Phylogenetic analyses showed an intrahost virus variation with some polymorphisms
      in envelope genes associated with different tissues. Conclusions and Relevance:
      Combined findings from clinical, laboratory, imaging, and pathological
      examinations provided a more complete picture of the severe damage and
      developmental abnormalities caused by ZIKV infection than has been previously
      reported. The term congenital Zika syndrome is preferable to refer to these
      cases, as microcephaly is just one of the clinical signs of this congenital
      malformation disorder.

PMID- 27695859
TI  - A 7-Year-Old Girl With Periorbital Edema, Ecchymosis, and Conjunctival
      Hemorrhage.

PMID- 27695862
TI  - Emerging Diagnostic and Therapeutic Tools for Central Nervous System Infections.

PMID- 27695863
TI  - JAMA Neurology at the Forefront, 1997-2016.

PMID- 27695864
TI  - Acta Dermatovenerologica Alpina, Pannonica et Adriatica accepted for coverage in
      Thomson Reuters' Emerging Sources Citation Index (ESCI).
AB  - Acta Dermatovenerologica Alpina, Pannonica et Adriatica (Acta Dermatovenerol APA)
      is the leading journal in dermatology and sexually transmitted infections in the
      region. Several important steps were taken during the last 25 years to improve
      the journal's quality, global visibility, and international impact. After a 1
      year trial period, Thomson Reuters recently informed the editorial office that
      they had accepted Acta Dermatovenerol APA for coverage in Thomson Reuters' new
      index in the Web of Science Core Collection called the Emerging Sources Citation
      Index (ESCI). The coverage of Acta Dermatovenerol APA begins with the journal
      content published online in 2016; that is, from volume 25 onwards.

PMID- 27695865
TI  - Efficacy and safety of 5% minoxidil topical foam in male pattern hair loss
      treatment and patient satisfaction.
AB  - INTRODUCTION: Male pattern hair loss is widespread around the world. Its
      prevalence indicates the importance of finding the best treatment modalities.
      This study evaluates the efficacy and safety of minoxidil 5% topical foam in male
      pattern hair loss treatment and patient satisfaction. METHODS: This study was a
      before-and-after trial on 17 male patients with male pattern hair loss. Subjects
      were instructed to apply one capful (1 ml) of minoxidil 5% topical foam on the
      scalp daily for 6 months. Efficacy was assessed through hair counts, subject
      assessment, and global photographic review. RESULTS: Seventeen male volunteers
      were recruited, and three volunteers were withdrawn; 14 participated in the trial
      for 16 weeks, and 12 continued up to 24 weeks. The average hair count with a
      camera at week 16 (181.87 +/- 52.42) and week 24 (194.58 +/- 62.82) and with an
      eye count at week 16 (62.57 +/- 15.28) and week 24 (69.91 +/- 15.61) increased
      significantly compared to the baseline after intervention. CONCLUSIONS: This
      study confirmed that minoxidil 5% topical foam is a safe and effective treatment
      for MPHL. The effect of it is evident after 24 weeks of use.

PMID- 27695866
TI  - Evaluation of hygiene habits: cross-sectional study.
AB  - Introduction:  It is well known that adequate hygiene is important for health.
      Even though this topic has drawn the attention of the media, little or no
      scientific investigation has been done. Methods: We performed a comparative
      questionnaire-based cross-sectional study in three groups: patients attending a
      dermatology outpatient clinic, patients attending an internal medicine
      consultation, and community members. Results: We analyzed a total of 446
      questionnaires (249 from dermatology patients, 98 from internal medicine
      patients, and 99 from the community group). The three groups did not differ
      statistically in sex and age (p=0.070). The patients from the dermatology
      department had a higher education level. The number of weekly baths did not
      differ among the three groups (p=0.417). Hair hygiene did not differ between the
      three groups. The dermatology and internal medicine groups washed their hands
      more frequently than the community group (p=0.028). Conclusions: Comparing our
      results to the limited data available, we find that the population surveyed has
      better hygiene habits than those previously reported. We believe that hygiene
      habits should be discussed during office visits.

PMID- 27695868
TI  - Surgical treatment of pyoderma gangrenosum following deep inferior epigastric
      perforator flap breast reconstruction.
AB  - Pyoderma gangrenosum is a chronic inflammatory disease characterized by painful
      cutaneous ulcers. The etiology remains unknown; however, pyoderma gangrenousm can
      be triggered by surgery. Here we report the case of a 34-year-old Caucasian
      female that developed pyoderma gangrenosum following deep inferior epigastric
      perforator flap breast reconstruction. The patient was successfully treated with
      systemic immunosuppressive therapy and primary closure.

PMID- 27695867
TI  - Hepatitis D virus infection in Slovenian patients with chronic hepatitis B virus
      infection: a national prevalence study and literature review.
AB  - INTRODUCTION: Of the 350 million individuals chronically infected with hepatitis
      B virus (HBV) worldwide, approximately 15 to 20 million have been exposed to
      hepatitis D virus (HDV). This study determined for the first time the HDV
      prevalence in Slovenian patients with chronic HBV infection. In addition, a
      literature search was performed to identify all HDV prevalence studies from
      European countries. METHODS: A total of 1,305 HBsAg-positive serum samples,
      obtained from the same number of patients, were randomly selected from 2,337
      patients referred to the Slovenian national reference laboratory for viral
      hepatitis between 1998 and 2015. All samples were retrospectively tested for the
      presence of total anti-HDV antibodies. Anti-HDV-positive patients were
      additionally tested for the presence of anti-HDV IgM antibodies, HDV antigen, and
      HDV RNA. RESULTS: Total anti-HDV antibodies were detected in three of the 1,305
      patients tested (0.23%; 95% CI: 0.08-0.67%), of whom one patient had recovered
      from the past HDV infection and two patients had an ongoing chronic HDV
      infection. The literature search identified 36 peer-reviewed HDV prevalence
      studies published between 1983 and 2016 and originating from 21 European
      countries. CONCLUSIONS: The observed prevalence of HDV infection in Slovenia was
      among the lowest reported in Europe and worldwide. Due to the observed low
      prevalence of HDV infection, routine diagnostic testing for HDV should not be
      considered in differential diagnosis of exacerbation of liver disease in
      Slovenian patients with chronic HBV infection.

PMID- 27695869
TI  - Very recent HIV infection accompanied by Pneumocystis jirovecii pneumonia and
      Mycobacterium avium complex immune reconstitution inflammatory syndrome: a case
      report.
AB  - A small proportion of HIV-infected patients rapidly progress to AIDS; indeed,
      some individuals have been known to progress to AIDS within a year after primary
      infection. Pneumonia caused by Pneumocystis jirovecii (PCP) is the most frequent
      AIDS-defining illness. However, PCP can also rarely occur during primary HIV
      infection as a result of the severe immunosuppression that may accompany the
      early stage of HIV infection. Immune reconstitution inflammatory syndrome (IRIS)
      comprises two distinct syndromes: paradoxical IRIS and unmasking IRIS. Infections
      with Mycobacterium avium complex during antiretroviral therapy are almost always
      localized and related to IRIS. We describe an unusual case of PCP and
      Mycobacterium avium complex-IRIS that occurred less than 3 months after primary
      HIV infection.

PMID- 27695870
TI  - Lamellar ichthyosis-like eruption associated with ponatinib.

PMID- 27695871
TI  - In Memoriam: Marija Bercic (1928-2016).

PMID- 27695872
TI  - Understanding cardiomyocyte proliferation: an insight into cell cycle activity.
AB  - Cardiomyocyte proliferation and regeneration are key to the functional recovery
      of myocardial tissue from injury. In the recent years, studies on cardiomyocyte
      proliferation overturned the traditional belief that adult cardiomyocytes
      permanently withdraw from the cell cycle activity. Hence, targeting cardiomyocyte
      proliferation is one of the potential therapeutic strategies for myocardial
      regeneration and repair. To achieve this, a deep understanding of the fundamental
      mechanisms involved in cardiomyocyte cell cycle as well as differences between
      neonatal and adult cardiomyocytes' cell cycle activity is required. This review
      focuses on the recent progress in understanding of cardiomyocyte cell cycle
      activity at different life stages viz., gestation, birth, and adulthood. The
      temporal expression/activities of major cell cycle activators (cyclins and CDKs),
      inhibitors (p21, p27, p57, p16, and p18), and cell-cycle-associated proteins (Rb,
      p107, and p130) in cardiomyocytes during gestation and postnatal life are
      described in this review. The influence of different transcription factors and
      microRNAs on the expression of cell cycle proteins is demonstrated. This review
      also deals major pathways (PI3K/AKT, Wnt/beta-catenin, and Hippo-YAP) associated
      with cardiomyocyte cell cycle progression. Furthermore, the postnatal alterations
      in structure and cellular events responsible for the loss of cell cycle activity
      are also illustrated.

PMID- 27695875
TI  - ?

PMID- 27695874
TI  - Pleiotropic regulations of neutrophil receptors response to sepsis.
AB  - INTRODUCTION: Sepsis is a complex clinical condition that causes a high mortality
      rate worldwide. Numerous studies on the pathophysiology of sepsis have revealed
      an imbalance in the inflammatory network, thus leading to tissue damage, organ
      failure, and ultimately death. The impairment of neu-trophil migration is
      associated with the outcome of sepsis. METHODS: Literature review was performed
      on the roles of neutrophil recruitment and neutrophil receptors as pleiotropic
      regulators during sepsis. Additionally, we systematically classify neutrophil
      receptors with regard to the neutrophil response during sepsis and discuss the
      clinical implications of these receptors for the treatment of sepsis. RESULTS:
      Increasing evidence suggests that there is significant dysfunction in neutrophil
      recruitment during sepsis, characterized by the failure to migrate to the site of
      infection. Neutrophil receptors, as pleiotropic regulators, play important roles
      in the neutrophil response during sepsis. CONCLUSIONS: Neutrophil receptors play
      key roles in chemotactic neutrophil migration and may prove to be suitable
      targets in future pharmacological therapies for sepsis.

PMID- 27695873
TI  - Determination of the connectivity of newborn neurons in mammalian olfactory
      circuits.
AB  - The mammalian olfactory bulb is a forebrain structure just one synapse downstream
      from the olfactory sensory neurons and performs the complex computations of
      sensory inputs. The formation of this sensory circuit is shaped through activity
      dependent and cell-intrinsic mechanisms. Recent studies have revealed that cell
      type specific connectivity and the organization of synapses in dendritic
      compartments are determined through cell-intrinsic programs already preset in
      progenitor cells. These progenitor programs give rise to subpopulations within a
      neuron type that have distinct synaptic organizations. The intrinsically
      determined formation of distinct synaptic organizations requires factors from
      contacting cells that match the cell-intrinsic programs. While certain genes
      control wiring within the newly generated neurons, other regulatory genes provide
      intercellular signals and are only expressed in neurons that will form contacts
      with the newly generated cells. Here, the olfactory system has provided a useful
      model circuit to reveal the factors regulating assembly of the highly structured
      connectivity in mammals.

PMID- 27695877
TI  - [When a name becomes a unit: Nikola Tesla].

PMID- 27695876
TI  - Genetic control of flowering time in rice: integration of Mendelian genetics and
      genomics.
AB  - KEY MESSAGE: Integration of previous Mendelian genetic analyses and recent
      molecular genomics approaches, such as linkage mapping and QTL cloning,
      dramatically strengthened our current understanding of genetic control of rice
      flowering time. Flowering time is one of the most important agronomic traits for
      seed production in rice (Oryza sativa L.). It is controlled mainly by genes
      associated with photoperiod sensitivity, particularly in short-day plants such as
      rice. Since the early twentieth century, rice breeders and researchers have been
      interested in elucidating the genetic basis of flowering time because its
      modification is important for regional adaptation and yield optimization.
      Although flowering time is a complex trait controlled by many quantitative trait
      loci (QTLs), classical genetic studies have shown that many associated genes are
      inherited in accordance with Mendelian laws. Decoding the rice genome sequence
      opened a new era in understanding the genetic control of flowering time on the
      basis of genome-wide mapping and gene cloning. Heading date 1 (Hd1) was the first
      flowering time QTL to be isolated using natural variation in rice. Recent
      accumulation of information on rice genome has facilitated the cloning of other
      QTLs, including those with minor effects on flowering time. This information has
      allowed us to rediscover some of the flowering genes that were identified by
      classical Mendelian genetics. The genes characterized so far, including Hd1, have
      been assigned to specific photoperiod pathways. In this review, we provide an
      overview of the studies that led to an in-depth understanding of the genetic
      control of flowering time in rice, and of the current state of improving and fine
      tuning this trait for rice breeding.

PMID- 27695878
TI  - [A hitchhiker's guide to the neuron galaxy : On the trail of the secrets of the
      brain with resting-state fMRI].

PMID- 27695881
TI  - [Secondary tendon reconstruction on the thumb].
AB  - Closed tendon ruptures of the thumb that require secondary reconstruction can
      affect the extensor pollicis longus (EPL), extensor pollicis brevis (EPB) and
      flexor pollicis longus (FPL) tendons. Treatment of rupture of the EPB tendon
      consists of refixation to the bone and temporary transfixation of the joint. In
      the case of preexisting or posttraumatic arthrosis, definitive arthrodesis of the
      thumb is the best procedure. Closed ruptures of the EPL and FPL tendons at the
      wrist joint cannot be treated by direct tendon suture. Rupture of the EPL tendon
      occurs after distal radius fractures either due to protruding screws or following
      conservative treatment especially in undisplaced fractures. Transfer of the
      extensor indicis tendon to the distal EPL stump is a good option and free
      interposition of the palmaris longus tendon is a possible alternative. The
      tension should be adjusted to slight overcorrection, which can be checked
      intraoperatively by performing the tenodesis test. Closed FPL ruptures at the
      wrist typically occur 3-6 months after osteosynthesis of distal radius fractures
      with palmar plates and are mostly characterized by crepitation and pain lasting
      for several weeks. They can be prevented by premature plate removal, synovectomy
      and carpal tunnel release. For treatment of a ruptured FPL tendon in adult
      patients the options for tendon reconstruction should be weighed up against the
      less complicated tenodesis or arthrodesis of the thumb interphalangeal joint.

PMID- 27695882
TI  - Angina, back pain and septic shock.

PMID- 27695880
TI  - [Current aspects of therapy of rhizoarthrosis].
AB  - In patients with carpometacarpal osteoarthritis of the thumb, treatment
      strategies should be based on functional impairment and pain. Although X-ray
      imaging is an integral component of the diagnostics, it is of subordinate
      importance for the therapy algorithm. Conservative therapy is always the first
      step in the chain of treatment. The efficacy of non-operative treatment,
      including intermittent immobilization using splinting and the application of
      technical assist devices in the daily routine has been proven to achieve pain
      relief. The intra-articular injection of hyaluronic acid or glucocorticoids is
      still under debate as some good experiences in routine clinical applications are
      contrasted by the lack of effectiveness in randomized studies. The indications
      for operative treatment are fulfilled by persisting pain after exhausting all the
      options for conservative therapy. In this case isolated trapeziectomy is the
      method of choice. Suspension (interpositioning) arthroplasty is not associated
      with improved clinical results. More recent procedures which aim to avoid
      proximalization by tendon interposition, have not yet shown better clinical
      outcome compared to trapeziectomy alone.

PMID- 27695879
TI  - Cyclin D1, cancer progression, and opportunities in cancer treatment.
AB  - Mammalian cells encode three D cyclins (D1, D2, and D3) that coordinately
      function as allosteric regulators of cyclin-dependent kinase 4 (CDK4) and CDK6 to
      regulate cell cycle transition from G1 to S phase. Cyclin expression,
      accumulation, and degradation, as well as assembly and activation of CDK4/CDK6
      are governed by growth factor stimulation. Cyclin D1 is more frequently
      dysregulated than cyclin D2 or D3 in human cancers, and as such, it has been more
      extensively characterized. Overexpression of cyclin D1 results in dysregulated
      CDK activity, rapid cell growth under conditions of restricted mitogenic
      signaling, bypass of key cellular checkpoints, and ultimately, neoplastic growth.
      This review discusses cyclin D1 transcriptional, translational, and post
      translational regulations and its biological function with a particular focus on
      the mechanisms that result in its dysregulation in human cancers.

PMID- 27695883
TI  - ICU specialists facing terrorist attack: the Nice experience.

PMID- 27695887
TI  - ?

PMID- 27695886
TI  - Co-management in geriatric hip fractures.

PMID- 27695888
TI  - ?

PMID- 27695885
TI  - [Treatment of neglect: new therapy approaches].
AB  - Neglect is a supramodal, clinically relevant disorder, which occurs in the
      different sensory modalities as well as in the mental representation. The
      different manifestations of neglect show interindividual and intraindividual
      variation. Different spatial and attention-related interventions lead to varying
      degrees of improvement in neglect symptoms but are often not stable in time or
      transferable to activities of daily living. Representational deficits or body
      related aspects to modify personal neglect are rarely a priority in current
      therapies. Because of the multisensory and motor deficits from our point of view
      the future of neglect rehabilitation lies in a combined therapy of visual
      exploration, motor imagery with intensive motor therapy of motor sensory deficits
      and probably best reinforced by continued neck muscle vibration or allocation of
      attention to the neglected side.

PMID- 27695889
TI  - ?

PMID- 27695884
TI  - Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy.
AB  - Sepsis is a major growing global burden and a major challenge to intensive care
      clinicians, researchers, guideline committee members and policy makers, because
      of its high and increasing incidence and great pathophysiological, molecular,
      genetic and clinical complexity. In spite of recent progress, short-term
      mortality remains high and there is growing evidence of long-term morbidity and
      increased long-term mortality in survivors of sepsis both in developed and
      developing countries. Further improvement in the care of patients with sepsis
      will impact upon global health. In this narrative review, invited experts
      describe the expected challenges and progress to be made in the near future. We
      focus on diagnosis, resuscitation (fluids, vasopressors, inotropes, blood
      transfusion and hemodynamic targets) and infection (antibiotics and infection
      biomarkers), as these areas are key, if initial management and subsequent
      outcomes are to be improved in patients with sepsis.

PMID- 27695890
TI  - Seeds of doubt: Mendel's choice of Hieracium to study inheritance, a case of
      right plant, wrong trait.
AB  - KEY MESSAGE: In this review, we explore Gregor Mendel's hybridization experiments
      with Hieracium , update current knowledge on apomictic reproduction and describe
      approaches now being used to develop true-breeding hybrid crops. From our
      perspective, it is easy to conclude that Gregor Mendel's work on pea was
      insightful, but his peers clearly did not regard it as being either very
      convincing or of much importance. One apparent criticism was that his findings
      only applied to pea. We know from a letter he wrote to Carl von Nageli, a leading
      botanist, that he believed he needed to "verify, with other plants, the results
      obtained with Pisum". For this purpose, Mendel adopted Hieracium subgenus
      Pilosella, a phenotypically diverse taxon under botanical study at the time. What
      Mendel could not have known, however, is that the majority of these plants are
      not sexual plants like pea, but instead are facultatively apomictic. In these
      forms, the majority of seed arises asexually, and such progeny are, therefore,
      clones of the maternal parent. Mendel obtained very few hybrids in his Hieracium
      crosses, yet we calculate that he probably emasculated in excess of 5000
      Hieracium florets to even obtain the numbers he did. Despite that effort, he was
      perplexed by the results, and they ultimately led him to conclude that "the
      hybrids of Hieracium show a behaviour exactly opposite to those of Pisum".
      Apomixis is now a topic of intense research interest, and in an ironic twist of
      history, Hieracium subgenus Pilosella has been developed as a molecular model to
      study this trait. In this paper, we explore further Mendel's hybridization
      experiments with Hieracium, update current knowledge on apomictic reproduction
      and describe approaches now being used to develop true-breeding hybrid crops.

PMID- 27695891
TI  - Speech audiometry, speech perception, and cognitive functions : English version.
AB  - Examination of cognitive functions in the framework of speech perception has
      recently gained increasing scientific and clinical interest. Especially against
      the background of age-related hearing impairment and cognitive decline, potential
      new perspectives in terms of a better individualization of auditory diagnosis and
      rehabilitation might arise. This review addresses the relationships between
      speech audiometry, speech perception, and cognitive functions. It presents models
      of speech perception, discusses associations of neuropsychological and
      audiometric outcomes, and shows examples of recent efforts undertaken in Germany
      to consider cognitive functions with speech audiometry.

PMID- 27695892
TI  - Grey Turner's sign associated with hemorrhagic pancreatitis.

PMID- 27695893
TI  - What is the prognosis of acute stroke patients requiring ICU admission?

PMID- 27695895
TI  - Renal replacement therapy modalities in the ICU: the continuity is intermittent
      response to comments by Schefold.

PMID- 27695894
TI  - A recovery program to improve quality of life, sense of coherence and
      psychological health in ICU survivors: a multicenter randomized controlled trial,
      the RAPIT study.
AB  - PURPOSE: The aim of this randomized controlled trial (RCT) was to test the
      effectiveness of a post-ICU recovery program compared to standard care during the
      first year after ICU discharge. METHODS: A pragmatic, non-blinded, multicenter,
      parallel-group RCT was conducted between December 2012 and December 2015, at ten
      intensive care units (ICUs) in Denmark. We randomly assigned 386 adult patients
      (>=18 years) after receiving mechanical ventilation (>=48 h) to standard care
      (SC) plus a nurse-led intensive care recovery program or standard care alone
      after ICU discharge (190 intervention, 196 SC). Primary outcome was health
      related quality of life (HRQOL) at 12 months. Secondary outcomes were sense of
      coherence (SOC), anxiety, depression, and post-traumatic stress disorder (PTSD)
      assessed at 3 and 12 months after ICU discharge including utilization of
      healthcare services at 12 months. RESULTS: At 12 months, we found no differences
      in HRQOL between groups (mean difference in the Physical Component Summary score,
      1.41 [95 % CI, -1.53 to 4.35; p = 0.35] (n = 235); and in the Mental Component
      Summary score, 1.92 [95 % CI, -1.06 to 4.90; p = 0.11] (n = 235). No differences
      were found on self-reported SOC (p = 0.63), anxiety (p = 0.68), depression (p =
      0.67), PTSD (p = 0.27), or the utilization of healthcare services including
      rehabilitation. We found a difference on anxiety, when a cut-off point >=11 was
      applied, in per protocol analysis of complete cases at 3 months favoring the
      intervention (8.8 % vs. 16.2 %, p = 0.04). CONCLUSIONS: The tested recovery
      program was not superior to standard care during the first 12 months post-ICU.
      TRIAL REGISTRATION: The trial is registered at Clinicaltrials.gov, identification
      no. NCT01721239.

PMID- 27695896
TI  - Renal replacement therapy modalities in the ICU: the continuity is intermittent.

PMID- 27695897
TI  - What's new in cognitive function in ICU survivors.

PMID- 27695898
TI  - Erratum to: The epigenetic signature of systemic insulin resistance in obese
      women.

PMID- 27695899
TI  - Sequential cleavage of insulin receptor by calpain 2 and gamma-secretase impairs
      insulin signalling.
AB  - AIMS/HYPOTHESIS: Soluble insulin receptor (sIR), the ectodomain of the insulin
      receptor (IR), has been detected in human plasma and its concentration paralleled
      that of blood glucose. We have previously developed an in vitro model using HepG2
      liver-derived cells, which mimics changes in sIR levels in plasma from diabetic
      patients and shows that calcium-dependent proteases cleave IR extracellularly (a
      process known as shedding). The present study aimed to reveal the mechanisms of
      IR cleavage. METHODS: Using the in vitro model, we investigated the molecular
      mechanisms of IR cleavage, which is accelerated by high-glucose treatment. We
      also analysed the relationship between IR cleavage and cellular insulin
      resistance, and the correlation between plasma sIR levels and insulin
      sensitivity, which was assessed by the euglycaemic-hyperinsulinaemic clamp
      technique. RESULTS: Here, we determined that calpain 2, which is secreted into
      the extracellular space associated with exosomes, directly cleaved the ectodomain
      of the IRbeta subunit (IRbeta), which in turn promoted intramembrane cleavage of
      IRbeta by gamma-secretase. IR cleavage impaired insulin signalling and the
      inhibition of IR cleavage (by knockdown of calpain 2 and gamma-secretase),
      restored IR substrate-1 and Akt, independent of IR. Furthermore, the glucose
      lowering drug, metformin, prevented IR cleavage accompanied by inhibition of
      calpain 2 release in exosomes, and re-established insulin signalling. In patients
      with type 2 diabetes, plasma sIR levels inversely correlated with insulin
      sensitivity. CONCLUSIONS/INTERPRETATION: Sequential cleavage of IR by calpain 2
      and gamma-secretase may contribute to insulin signalling in cells and its
      inhibition may be partly responsible for the glucose-lowering effects of
      metformin. Thus, IR cleavage may offer a new mechanism for the aetiology of
      insulin resistance.

PMID- 27695900
TI  - An oxidative stress paradox: time for a conceptual change?
AB  - Oxidative stress has long been considered a key driving factor of many obesity
      related health problems. However, recent work by Merry, Tran et al (Diabetologia
      DOI 10.1007/s00125-016-4084-3 ) challenges this idea with an interesting study
      using a hepatocyte-specific Gpx1-knockout (HGKO) mouse. GPX1 is an important
      detoxification enzyme that converts H2O2 to water. The authors found that high
      fat diet-fed HGKO mice were more insulin sensitive than wildtype controls,
      despite elevated hepatic levels of H2O2 and evidence of increased systemic
      oxidative stress. When challenged with a non-alcoholic steatohepatitis (NASH)
      inducing diet, HGKO mice were also protected, displaying reduced levels of
      inflammation and fibrosis with similar levels of steatosis compared with
      controls. These findings call into question the role of reactive oxygen species
      in NASH pathogenesis and highlight a potential paradox whereby increased H2O2 may
      be beneficial in some contexts.

PMID- 27695901
TI  - Trends in childhood measles vaccination highlight socioeconomic inequalities in
      Vietnam.
AB  - OBJECTIVES: To describe trends in measles vaccine coverage rates and their
      association with socioeconomic characteristics among children from age 12 to 23
      months in Vietnam from the year 2000 to 2014. METHODS: Data were drawn from the
      Vietnam Multiple Indicator Cluster Surveys in years 2000, 2006, 2011, and 2014.
      Concentration indices were used to determine the magnitude of socioeconomic
      inequalities in measles vaccine coverage. Associations between measles vaccine
      coverage and relevant social factors were assessed using logistic regression.
      RESULTS: Socioeconomic inequalities in measles vaccine coverage rates decreased
      during 2000-2014. Children belonging to ethnic minority groups, having mothers
      with lower education, and belonging to the poorest group were less likely to
      receive measles vaccine; although, their vaccine coverage rates did increase with
      time. Measles vaccine coverage declined among children of mothers with more
      education and belonging to the wealthiest socioeconomic group. CONCLUSIONS:
      Understanding the social factors influencing adherence to recommend childhood
      vaccination protocols is essential. Attempts to regain and retain herd immunity
      must be guided by an understanding of these social factors if they are to
      succeed.

PMID- 27695902
TI  - Caterpillar hairs as an anti-parasitoid defence.
AB  - Caterpillar hairs are thought to act as a physical barrier against natural
      enemies, including parasitoids. However, very few studies have experimentally
      demonstrated how hairs protect caterpillars from parasitoid oviposition. To
      clarify the importance of caterpillar hairs as an anti-parasitoid defence, we
      observed the generalist endoparasitoid Meteorus pulchricornis (Hymenoptera:
      Braconidae) attacking both smooth and hairy caterpillars under laboratory
      conditions. A female Meteorus pulchricornis uses its ovipositor to inject venom
      and lay a single egg inside host larvae. We placed a smooth Spodoptera litura
      (Lepidoptera: Noctuidae) caterpillar or a hairy Lymantria dispar japonica
      (Lepidoptera: Erebidae) caterpillar in front of parasitoid females. We observed
      that 100 % and 84 % of the parasitoids could successfully stab their ovipositors
      into the smooth larvae of S. litura and first instars of the hairy caterpillar L.
      dispar japonica, respectively. However, only 24 % of parasitoids could
      successfully stab their ovipositors into second-instar L. dispar japonica. A
      higher rate of successful stabs (94 %) by parasitoids was obtained by cutting the
      hairs of second instar L. dispar japonica much shorter than the parasitoid
      ovipositor. The results demonstrate that the long, thick hairs of second and
      later instars of L. dispar japonica function as a physical barrier against
      parasitoid oviposition.

PMID- 27695903
TI  - Variation in nesting behavior of eight species of spider mites, Stigmaeopsis
      having sociality.
AB  - Nesting behavior is considered to be an important element of social living in
      animals. The spider mites belonging to the genus Stigmaeopsis spend their lives
      within nests produced from silk threads. Several of these species show
      cooperative sociality, while the others are subsocial. In order to identify the
      origins of this social behavior, comparisons of nest sizes, nesting behaviors
      (making nests continuously or separately), and their associated traits (fecal
      deposition patterns) were made for eight cogeneric Stigmaeopsis species showing
      various levels of social development. All of these species inhabit bamboo plants
      (Poaceae). We initially addressed the proximate factor of nest size variation.
      The variation in nest size of the eight species corresponded well with the
      variation in dorsal seta sc1 length, suggesting that nest size variation among
      species may have a genetic basis. The time spent within a nest (nest duration)
      increased with nest size on the respective host plants. Nest arrangement patterns
      varied among species showing different sized nests: Large nest builders
      continuously extended their nests, while middle and small nest-building species
      built new separate nests, which resulted in different social interaction times
      among species, and is thought to be closely related to social development. Fecal
      deposition behaviors also varied among Stigmaeopsis species, suggesting diversity
      in anti-predatory adaptations. Finally, we discuss how the variation in sociality
      observed within this genus is likely the result of nest size variation that
      initially evolved as anti-predator strategies.

PMID- 27695904
TI  - Articular cartilage paste graft for severe osteochondral lesions of the knee: a
      10- to 23-year follow-up study.
AB  - PURPOSE: The purpose of this study is to evaluate the clinical outcomes of the
      articular cartilage paste graft procedure at a minimum of 10 years from surgery.
      It is hypothesized that articular cartilage paste grafting can provide patients
      with a durable repair of severe full-thickness osteochondral injuries, measured
      by persistence of procedure-induced benefit and subjective outcome scores at 10
      or more years. METHODS: Seventy-four patients undergoing paste grafting at a mean
      age of 45.3 +/- 10.8 years (range 13-69 years) were followed up at a mean of 16.8
      +/- 2.4 years (range 10.6-23.2 years) post-operatively using validated subjective
      outcome measures; Kaplan-Meier survival analysis was performed to estimate
      expected population benefit time. RESULTS: Kaplan-Meier estimated median benefit
      time of 19.1 years (mean: 16.6 +/- 0.9 years) for all patients undergoing paste
      grafting. Thirty-one (41.9 %) patients had progressed to arthroplasty at a mean
      of 9.8 +/- 5.6 years (range 0.4-20.6 years). Ninety percent of patients reported
      that the procedure provided good to excellent pain relief. Median IKDC subjective
      score increased significantly at most recent follow-up (70.1) compared to
      preoperative (55.7, p = 0.013). Median WOMAC scores decreased significantly from
      26 to 14 (p = 0.001). Median Tegner score increase from 4 to 6 was not found to
      be significant (ns). VAS pain averaged 23/100 at most recent follow-up.
      CONCLUSIONS: Patients who underwent the paste grafting reported improved pain,
      function, and activity levels for an expected mean of 16.6 years, and for those
      who ultimately progressed to knee replacement, surgical treatment including the
      paste graft was able to delay arthroplasty until a mean age of 60.2 years, an age
      at which the procedure is commonly performed. Full-thickness articular cartilage
      loss can be successfully treated, reducing pain, and improving function, using
      this single-step, inexpensive arthroscopic procedure. LEVEL OF EVIDENCE: IV.

PMID- 27695905
TI  - The efficacy of post-operative devices following knee arthroscopic surgery: a
      systematic review.
AB  - PURPOSE: There is a wide array of device modalities available for post-operative
      treatment following arthroscopic knee surgery; however, it remains unclear which
      types and duration of modality are the most effective. This systematic review
      aimed to investigate the efficacy of device modalities used following
      arthroscopic knee surgery. METHODS: A systematic search of the literature was
      performed on: PubMed; Scopus; MEDLINE; EMBASE; PEDro; SportDiscus; and CINAHL
      databases (1995-2015) for clinical trials using device modalities following
      arthroscopic knee surgery: cryotherapy, continuous passive motion (CPM),
      neuromuscular electrical stimulation (NMES), surface electromyographic (sEMG)
      biofeedback and shockwave therapy (ESWT). Only level 1 and 2 studies were
      included and the methodological quality of studies was evaluated using
      Physiotherapy Evidence Database (PEDro) scores. Outcome measures included: muscle
      strength, range of motion, swelling, blood loss, pain relief, narcotic use, knee
      function evaluation and scores, patient satisfaction and length of hospital stay.
      RESULTS: Twenty-five studies were included in this systematic review, nineteen of
      which found a significant difference in outcomes. For alleviating pain and
      decreasing narcotic consumption following arthroscopic knee surgery,
      cryocompression devices are more effective than traditional icing alone, though
      not more than compression alone. CPM does not affect post-operative outcomes.
      sEMG biofeedback and NMES improve quadriceps strength and overall knee functional
      outcomes following knee surgery. There is limited evidence regarding the effects
      of ESWT. CONCLUSION: Cryotherapy, NMES and sEMG are recommended for inclusion
      into rehabilitation protocols following arthroscopic knee surgery to assist with
      pain relief, recovery of muscle strength and knee function, which are all
      essential to accelerate recovery. CPM is not warranted in post-operative
      protocols following arthroscopic knee surgery because of its limited
      effectiveness in returning knee range of motion, and additional studies are
      required to investigate the effects of ESWT. LEVEL OF EVIDENCE: II.

PMID- 27695906
TI  - Is there a distinct pattern to the acetabular labrum and articular cartilage
      damage in the non-dysplastic hip with instability?
AB  - PURPOSE: The purpose of this study was to determine whether or not there is a
      distinct pattern of injury to the acetabular labrum and/or cartilage in the hip
      with instability without bony dysplasia. METHODS: Surgical records and intra
      operative images of consecutive patients who underwent primary hip arthroscopy
      for femoroacetabular impingement (FAI) and/or hip instability by the senior
      author from April 2007 to December 2014 were retrospectively reviewed.
      Pathological changes were documented and charted on a novel diagram of the
      acetabulum, and classified into eight patterns corresponding to the lesion's
      location and size. In patients who had acetabular chondroplasty treatment, the
      width of the cartilage lesion was recorded. RESULTS: A total of 953 hips in 886
      patients were included, and patients who met our inclusion/exclusion criterion
      were grouped into an Instability-Only group (45 hips), an Instability-Dysplasia
      group (12 hips), as well as Pincer-FAI, Cam-FAI, and Combined-FAI groups
      consisting of 100, 54, and 269 hips, respectively. In the Instability-Only group,
      42.2 % of the chondral and labral lesions demonstrated a "Straight-Anterior"
      pattern, which proportion was statistically significantly different compared with
      Pincer-FAI (p < 0.000), Cam-FAI (p = 0.0002), and Combined-FAI (p < 0.000)
      groups. In Instability-Only patients, only 15.6 % of the lesions had an "Anterior
      to Lateral" pattern, a significantly lower proportion (p < 0.000) compared with
      the FAI groups. Also 11.1 % of the lesions demonstrated a "Lateral" pattern,
      which is a significantly greater proportion compared with Pincer-FAI (p < 0.000)
      and Combined-FAI (p < 0.000) groups. The mean width of the cartilage lesions for
      the Instability-Only group was 2.9 mm, which was significantly shallower than for
      the other FAI groups (p < 0.000). CONCLUSION: A significant predilection of
      "Straight-Anterior" or "Lateral" location of labral and/or cartilage damage was
      observed in the hip with instability, while there was shallow width of articular
      cartilage damage in these patients. These results suggest that there is a
      distinctive labral and cartilage damage pattern for hips with instability without
      inherent bony dysplasia. LEVEL OF EVIDENCE: Diagnostic study, Level IV.

PMID- 27695907
TI  - Cochliobolus lunatus down-regulates proteome at late stage of colonization and
      transiently alters StNPR1 expression in Solanum tuberosum L.
AB  - Cochliobolus lunatus abundantly produces four-celled conidia at high temperatures
      (>30  degrees C) and under suitable conditions; the fungus colonizes potato
      (Solanum tuberosum L.) cultivars by adopting different invasion strategies at the
      microscopic level. Long-lasting defence during infection requires an upsurge in
      proteome changes particularly pathogenesis-related proteins chiefly under the
      control of nonexpresser of pathogenesis-related proteins. In order to gain
      molecular insights, we profiled the changes in proteome and potato nonexpresser
      of pathogenesis-related proteins (StNPR1) during the infection process. It is
      found that C. lunatus significantly (P < 0.05) suppressed the host functional
      proteome by 96 h after infection (hai), principally, affecting the expression of
      ribulose bisphosphate carboxylase enzyme, plastidic aldolase enzyme, alcohol
      dehydrogenase 2 and photosystem II protein prior to the formation of brown-to
      black leaf spot disease. Strongest host response was observed at 24 hai
      hallmarked by 307 differentially expressed peptide spots concurring with the
      active phase of production of penetrating hyphae. Additionally, C. lunatus
      differentially down-regulated StNPR1 transcript by 8.19 fold by 24 hai. This
      study is the first to elucidate that C. lunatus transiently down-regulates the
      expression of StNPR1 at the onset of infection, and as a whole, infection
      negatively affects the expression of proteome components involved in
      photosynthesis, carbon fixation and light assimilation. This study contributes
      towards better understanding of the mechanism underlining the invasion strategies
      of C. lunatus.

PMID- 27695908
TI  - Reply to Rahbar K et al.

PMID- 27695909
TI  - Segmental 18F-FDG-PET/CT in a single pulmonary nodule: a better
      cost/effectiveness strategy.

PMID- 27695911
TI  - Molecular analysis of the role of osmolyte transporters opuCA and betL in
      Listeria monocytogenes after cold and freezing stress.
AB  - Listeria monocytogenes is a food-borne pathogen of humans and other animals. The
      striking ability to survive several stresses usually used for food preservation
      makes L. monocytogenes one of the biggest concerns to the food industry. This
      ubiquity can be partly explained by the ability of the organism to grow and
      persist at very low temperatures, a consequence of its ability to accumulate
      cryoprotective compound called osmolytes. A quantitative RT-PCR assay was used to
      measure mRNA transcript accumulation for the stress response genes opuCA and betL
      (encoding carnitine and betaine transporters, respectively) and the housekeeping
      gene 16S rRNA. Assays were conducted on mid-exponential phase L. monocytogenes
      cells exposed to conditions reflecting cold and freezing stress, conditions
      usually used to preserve foods. We showed that expression of the two cold-adapted
      genes encoded the transporters of the cryoprotectants carnitine and betaine in
      ATCC 19115 and the food-isolated L. monocytogenes S1 is induced after cold and
      freezing stress exposure. Furthermore, transcriptional analysis of the genes
      encoding opuCA and betL revealed that each transporter is induced to different
      degrees upon cold shock of L. monocytogenes ATCC 19115 and S1. Our results
      confirm an increase in carnitine uptake at low temperatures more than in betaine
      after cold-shocked temperature compared to the non-stress control treatment. It
      was concluded the use of carnitine and betaine as cryoprotectants is essential
      for rapid induction of the tested stress response under conditions typically
      encountered during food preservation.

PMID- 27695910
TI  - A comparative study of the evolution of cellobiose utilization in Escherichia
      coli and Shigella sonnei.
AB  - The chb operon of Escherichia coli is involved in the utilization of
      chitooligosaccharides. While acquisition of two classes of mutations leading to
      altered regulation of the chb operon is necessary to confer the ability to
      utilize the glucose disaccharide cellobiose to wild-type strains of E. coli, in
      the closely related organism Shigella sonnei, Cel+ mutants arise relatively
      faster, requiring only a single mutational event. In Type I mutants, the
      insertion of IS600 at -21 leads to ChbR regulator-independent, constitutive
      expression of the operon. In Type II mutants, the insertion of IS2/600 within the
      distal binding site of the negative regulator NagC leads to ChbR-dependent
      cellobiose-inducible expression of the operon. These studies underscore the
      significance of strain background, specifically the diversity of transposable
      elements, in the evolution of novel metabolic functions. Constitutive expression
      of the chb operon also enables utilization of the aromatic beta-glucosides
      arbutin and salicin, implying that the chb structural genes are inherently
      promiscuous.

PMID- 27695912
TI  - Effects of integrated feedback on discrete bimanual movements in choice reaction
      time.
AB  - The ability to coordinate the simultaneous movements of our arms is limited by a
      coalition of constraints. Some of these constraints can be overcome when the task
      conceptualisation is improved. The present study investigated how the movement
      preparation of bimanual reaching movements was affected by integrated visual
      feedback of the responses. Previous research has shown that the preparation of
      bimanual asymmetric movements takes longer than bimanual symmetric movements. The
      goal of the present study was to determine whether integrated, Lissajous feedback
      could eliminate this bimanual asymmetric cost. Fifteen participants made
      unimanual and bimanual symmetric and asymmetric reaches with separate feedback,
      where there was a cursor and a target for each hand. Participants also made
      bimanual symmetric and asymmetric movements with integrated feedback; a single
      cursor and a single target represented the locations and goals of both arms in
      this condition. The results showed a bimanual asymmetric cost with separate
      feedback, and that this cost persisted with integrated feedback. We suggest that
      integrated feedback improved continuous and discrete bimanual movements in other
      experiments by facilitating error detection and correction processes. We
      hypothesise that the bimanual asymmetric cost persisted in the present experiment
      because the uncertainty associated with choice reaction time prevented the
      facilitated error processing from improving the preparation of the next trial.

PMID- 27695914
TI  - Brain natriuretic peptide for prevention of contrast-inducednephropathy: a meta
      analysis of randomized controlled trials.
AB  - PURPOSE: Contrast-induced nephropathy (CIN) is a serious complication and
      associated with poor clinical outcomes. The protective value of brain natriuretic
      peptide (BNP) administration on CIN is still controversial in patients undergoing
      percutaneous coronary intervention (PCI) or coronary angiography (CAG). We
      performed a meta-analysis of randomized controlled trials (RCTs) for BNP in
      preventing CIN. METHODS: We systematically searched PubMed, Web of Science,
      Cochrane Library, and ClinicalTrials.gov for RCTs comparing administration of BNP
      versus non-BNP for preventing CIN. Publication bias was assessed by funnel plots.
      Relative risk (RR) was calculated for incidence of CIN and major adverse
      cardiovascular events (MACEs) using the random or fixed effect model according to
      heterogeneity analysis. RESULTS: There were five RCTs with 1441 patients in this
      analysis. BNP treatment was associated with lower incidence of CIN (RR = 0.38, 95
      % CI 0.27-0.54, p < 0.001) and MACEs (RR = 0.47, 95 % CI 0.24-0.95, p = 0.034)
      with no significant heterogeneity (I 2 = 0 %, p = 0.701; I 2 = 60 %, p = 0.113,
      respectively). Similar results were seen in subgroup analysis. Prophylactic BNP
      significantly decreased the incidence of CIN after cardiac catheterization in the
      studies of regarding sodium chloride as placebo (I 2 = 0 %, RR = 0.39, 95 % CI
      0.27-0.56, p < 0.001) or JADAD score > 3 (I 2 = 0 %, RR = 0.38, 95 % CI 0.21
      0.68, p = 0.001). CONCLUSIONS: Preprocedural BNP treatment significantly
      decreased the incidence of CIN and short-term MACEs in patients undergoing PCI or
      CAG.

PMID- 27695915
TI  - Amoxicillin-clavulanic acid and ciprofloxacin-treated SPF mice as gnotobiotic
      model.
AB  - The experiment was carried out on 24 SPF BALB/c female mice and lasted for 15
      days with a 5-day antibiotic (ATB) treatment and then 10 days without ATB
      treatment. The aim of our study was to acquire an animal model with reduced and
      controlled microflora and, at the same time, to ensure that the good health of
      these animals is maintained. Per oral administration of amoxicillin and
      clavulanate potassium in Amoksiklav (Sandoz, Slovenia) at a dose of 387.11 mg/kg
      body weight (0.2 ml of dilution per mouse) and subcutaneous administration of
      ciprofloxacin in Ciloxan (Alcon, Spain) at a dose of 18.87 mg/kg body weight (0.1
      ml of dilution per mouse) were performed every 12 h during first 5 days of
      experiment. Five-day treatment with ATB led to a reduced survivability of
      microorganisms in faeces (28.33 +/- 0.43 % on day 2) and caecum content (28.10 +/
      1.56 %), where no cultivable microorganisms in faeces were present. Ten-day
      convalescence of decontaminated animals under gnotobiotic conditions prevented
      recovery of species diversity in mice gut microflora. This was reduced to two
      detectable cultivable species, namely Escherichia coli (GenBank KX086704) and
      Enterococcus sp. (GenBank KX086705) which were capable to restore its metabolic
      (CRL 2012) and morphological potential (Baratta et al. Histochem Cell Biol
      131:713-726, 2009) within physiological range. Animals obtained under this
      procedure can be used in further studies. As a result, we created a mouse gnoto
      model with reduced and controlled microflora without alteration of the overall
      health status of the respective animals.

PMID- 27695913
TI  - Footprint area analysis of binary imaged Cupriavidus necator cells to study PHB
      production at balanced, transient, and limited growth conditions in a cascade
      process.
AB  - Statistical distribution of cell and poly[3-(R)-hydroxybutyrate] (PHB) granule
      size and number of granules per cell are investigated for PHB production in a
      five-stage cascade (5CSTR). Electron microscopic pictures of cells from
      individual cascade stages (R1-R5) were converted to binary pictures to visualize
      footprint areas for polyhydroxyalkanoate (PHA) and non-PHA biomass. Results for
      each stage were correlated to the corresponding experimentally determined
      kinetics (specific growth rate MU and specific productivity pi). Log-normal
      distribution describes PHA granule size dissimilarity, whereas for R1 and R4,
      gamma distribution best reflects the situation. R1, devoted to balanced biomass
      synthesis, predominately contains cells with rather small granules, whereas with
      increasing residence time tau, maximum and average granule sizes by trend
      increase, approaching an upper limit determined by the cell's geometry.
      Generally, an increase of intracellular PHA content and ratio of granule to cell
      area slow down along the cascade. Further, the number of granules per cell
      decreases with increasing tau. Data for MU and pi obtained by binary picture
      analysis correlate well with the experimental results. The work describes long
      term continuous PHA production under balanced, transient, and nutrient-deficient
      conditions, as well as their reflection on the granules size, granule number, and
      cell structure on the microscopic level.

PMID- 27695916
TI  - Taxonomical and functional microbial community dynamics in an Anammox-ASBR system
      under different Fe (III) supplementation.
AB  - In the present study, we explored the metabolic versatility of anaerobic ammonium
      oxidation (anammox) bacteria in a variety of Fe (III) concentrations.
      Specifically, we investigated the impacts of Fe (III) on anammox growth rates, on
      nitrogen removal performance, and on microbial community dynamics. The results
      from our short-term experiments revealed that Fe (III) concentrations (0.04-0.10
      mM) significantly promote the specific anammox growth rate from 0.1343 to 0.1709
      d-1. In the long-term experiments, the Anammox-anaerobic sequencing batch reactor
      (ASBR) was operated over 120 days and achieved maximum NH4+-N, NO2--N, and TN
      efficiencies of 90.98 +/- 0.35, 93.78 +/- 0.29, and 83.66 +/- 0.46 %,
      respectively. Pearson's correlation coefficients between anammox-(narG + napA),
      anammox-nrfA, and anammox-FeRB all exceeded r = 0.820 (p < 0.05), confirming an
      interaction and ecological association among the nitrogen and iron-cycling
      related microbial communities. Illumina MiSeq sequencing indicated that
      Chloroflexi (34.39-39.31 %) was the most abundant phylum in an Anammox-ASBR
      system, followed by Planctomycetes (30.73-35.31 %), Proteobacteria (15.40-18.61
      %), and Chlorobi (4.78-6.58 %). Furthermore, we found that higher Fe (III)
      supplementation (>0.06 mM) could result in the community succession of anammox
      species, in which Candidatus Brocadia and Candidatus Kuenenia were the dominant
      anammox bacteria species. Combined analyses indicated that the coupling of
      anammox, dissimilatory nitrogen reduction to ammonium, and iron reduction
      accounted for nitrogen loss in the Anammox-ASBR system. Overall, the knowledge
      gained in this study provides novel insights into the microbial community
      dynamics and metabolic potential of anammox bacteria under Fe (III)
      supplementation.

PMID- 27695917
TI  - Elucidating the origin of HLA-B*73 allelic lineage: Did modern humans benefit by
      archaic introgression?
AB  - A previous study reported that some of the human leukocyte antigen (HLA) alleles
      and haplotypes in present-day humans were acquired by admixture with archaic
      humans; specifically, an exceptionally diverged HLA-B*73 allele was proposed to
      be transmitted from Denisovans, although the DNA sequence of HLA-B*73 has not
      been detected in the Denisovan genome. Here, we argue against the hypothesis that
      HLA-B*73 introgressed from Denisovans into early modern humans. A phylogenetic
      analysis revealed that HLA-B*73:01 formed a monophyletic group with a chimpanzee
      MHC-B allele, strongly suggesting that the HLA-B*73 allelic lineage has been
      maintained in humans as well as in chimpanzees since the divergence of humans and
      chimpanzees. The global distribution of HLA-B*73 allele showed that the
      population frequency of HLA-B*73 in west Asia (0.24 %)-a possible site of
      admixture with Denisovans-is lower than that in Europe (0.72 %) and in south Asia
      (0.69 %). Furthermore, HLA-B*73 is not observed in Melanesia even though the
      Melanesian genome contains the highest proportion of Denisovan ancestry in
      present-day human populations. Single nucleotide polymorphisms in HLA-A*11-HLA
      C*12:02 or HLA-A*11-C*15 haplotypes, one of which was assumed to be transmitted
      together with HLA-B*73 from Denisovans by the study of Abi-Rached and colleagues,
      were not differentiated from those in other HLA-A-C haplotypes in modern humans.
      These results do not support the introgression hypothesis. Thus, we conclude that
      it is highly likely that HLA-B*73 allelic lineage has been maintained in the
      direct ancestors of modern humans.

PMID- 27695918
TI  - Assessing adherence to inhaled corticosteroids in asthma patients using an
      integrated measure based on primary and secondary adherence.
AB  - PURPOSE: There are very few studies on primary adherence (i.e., first filling of
      a prescription) to inhaled corticosteroids (ICS) in asthma patients; two have
      involved children. Moreover, adherence can be overestimated when considering only
      secondary adherence (i.e., following the medication recommendations for a defined
      period) and ignoring primary adherence. We aimed thus to evaluate the real-world
      primary and secondary adherence to ICS and to develop an integrated primary and
      secondary adherence (IPSA) measure. METHODS: From two clinical databases of
      pediatric and adult asthma patients, we included 198 children and 206 adults with
      one ICS prescription recorded in their medical chart between 2010 and 2012 and
      follow-up data for >=12 months. Adherence was estimated from written
      prescriptions and prescription claims data. Primary adherence was defined as
      filling the ICS prescription at a pharmacy within 12 months. Secondary adherence
      was defined as the proportion of days covered (PDC) in subjects who filled their
      prescription at least once. The IPSA was based on the PDC with a correction
      factor for primary adherence. RESULTS: Primary adherence to ICS at 12 months was
      89.4 % in children and 69.4 % in adults. Secondary adherence at 12 months in
      children was 33.9 %, and the IPSA was 30.3 %. These values were 52.8 and 36.6 %,
      respectively, in adults. CONCLUSIONS: Primary adherence to ICS is low in adults
      and secondary adherence is poor in children and adults. Using the PDC as a unique
      measure of adherence led to significant overestimation in adults; IPSA leads to
      more valid estimates of adherence to ICS.

PMID- 27695920
TI  - Acute posterior thigh pain in an athlete. Grade I myofascial strain of an
      accessory muscular slip and adjoining muscle fibres, connecting an accessory
      tensor fascia suralis (TFS) muscle and the distal biceps femoris.

PMID- 27695919
TI  - A machine-learned computational functional genomics-based approach to drug
      classification.
AB  - OBJECTIVE: The public accessibility of "big data" about the molecular targets of
      drugs and the biological functions of genes allows novel data science-based
      approaches to pharmacology that link drugs directly with their effects on
      pathophysiologic processes. This provides a phenotypic path to drug discovery and
      repurposing. This paper compares the performance of a functional genomics-based
      criterion to the traditional drug target-based classification. METHODS: Knowledge
      discovery in the DrugBank and Gene Ontology databases allowed the construction of
      a "drug target versus biological process" matrix as a combination of "drug versus
      genes" and "genes versus biological processes" matrices. As a canonical example,
      such matrices were constructed for classical analgesic drugs. These matrices were
      projected onto a toroid grid of 50 * 82 artificial neurons using a self
      organizing map (SOM). The distance, respectively, cluster structure of the high
      dimensional feature space of the matrices was visualized on top of this SOM using
      a U-matrix. RESULTS: The cluster structure emerging on the U-matrix provided a
      correct classification of the analgesics into two main classes of opioid and non
      opioid analgesics. The classification was flawless with both the functional
      genomics and the traditional target-based criterion. The functional genomics
      approach inherently included the drugs' modulatory effects on biological
      processes. The main pharmacological actions known from pharmacological science
      were captures, e.g., actions on lipid signaling for non-opioid analgesics that
      comprised many NSAIDs and actions on neuronal signal transmission for opioid
      analgesics. CONCLUSIONS: Using machine-learned techniques for computational drug
      classification in a comparative assessment, a functional genomics-based criterion
      was found to be similarly suitable for drug classification as the traditional
      target-based criterion. This supports a utility of functional genomics-based
      approaches to computational system pharmacology for drug discovery and
      repurposing.

PMID- 27695922
TI  - Comparing and refining karst disturbance index methods through application in an
      island karst setting.
AB  - The interconnected nature of surface and subsurface karst environments allows
      easy disturbance to their aquifers and specialized ecosystems from anthropogenic
      impacts. The karst disturbance index is a holistic tool used to measure
      disturbance to karst environments and has been applied and refined through
      studies in Florida and Italy, among others. Through these applications, the karst
      disturbance index has evolved into two commonly used methods of application; yet,
      the karst disturbance index is still susceptible to evaluation and modification
      for application in other areas around the world. The geographically isolated and
      highly vulnerable municipality of Arecibo, Puerto Rico's karst area provides an
      opportunity to test the usefulness and validity of the karst disturbance index in
      an island setting and to compare and further refine the application of the
      original and modified methods. This study found the both methods of karst
      disturbance index application resulted in high disturbance scores (Original
      Method 0.54 and Modified Method 0.69, respectively) and uncovered multiple
      considerations for the improvement of the karst disturbance index. An evaluation
      of multiple methods together in an island setting also resulted in the need for
      adding additional indicators, including Mogote Removal and Coastal Karst.
      Collectively, the results provide a holistic approach to using the karst
      disturbance index in an island karst setting and suggest a modified method by
      which scaling and weighting may compensate for the difference between the
      original and modified method scores and allow interested stakeholders to evaluate
      disturbance regardless of his or her level of expertise.

PMID- 27695921
TI  - Sex differences and the role of dopamine receptors in the reward-enhancing
      effects of nicotine and bupropion.
AB  - RATIONALE: Nicotine and bupropion have been demonstrated to enhance the value of
      other reinforcers, and this may partially account for nicotine reward and
      dependence. Evidence suggests that the sexes differ in their sensitivity to the
      primary and secondary reinforcing effects of nicotine and nicotine-associated
      stimuli. Whether the sexes also differ in sensitivity to the reward-enhancing
      effects of nicotine (and bupropion) is yet unclear. OBJECTIVES: The present study
      evaluated potential sex differences in the enhancement effects of nicotine and
      bupropion using a reinforcer demand approach. Furthermore, we sought to
      investigate the role that D1- and D2-type dopamine receptors play in the reward
      enhancing effects of nicotine and bupropion. METHODS: Demand for sensory
      reinforcement was assessed in male and female rats responding on a progression of
      fixed ratio schedules. The effects of nicotine and 10 or 20 mg/kg bupropion on
      reinforcer demand were assessed within subjects. Subsequently, the effects of SCH
      23390 and eticlopride were assessed on the enhancing effects of nicotine and
      bupropion on progressive ratio responding. RESULTS: Nicotine and bupropion
      enhanced demand metrics of reinforcement value in both sexes. Females were more
      sensitive to the enhancement effects of bupropion assessed by reinforcer demand
      and progressive ratio performance. D2-like dopamine receptor antagonism by
      eticlopride attenuated the enhancement effects of bupropion, but not of nicotine.
      CONCLUSIONS: Nicotine and bupropion both enhance reinforcement value in both
      sexes, though females may be more sensitive to the reward-enhancing effects of
      bupropion. D2- and possibly D1-type receptors appear to be involved in the reward
      enhancing effects of bupropion, but not necessarily nicotine.

PMID- 27695923
TI  - Characterization of Coastal Drift-Cell Sediment Processes Effecting the
      Restoration of the Southern Lake Michigan Shoreline.
AB  - Hard structures along the southern shore of Lake Michigan restrict natural
      longshore sediment transport, destabilizing the shoreline, and dissecting the
      coast into localized shoreline reaches. A geometric design was used to sample (n
      = 590 nodes) at nine shoreline reaches near the Indiana Dunes National Lakeshore
      to characterize existing sediment in the offshore and onshore zones. Cluster
      Analysis grouped shoreline sites into two clusters. Factor Analysis showed that
      35 % of the sand fractionation's cumulative variance across all sites was
      explained by an increased loading on medium sand (0.250 mm) with a corresponding
      decrease loading on small pebbles (4.750 mm), and an additional 30 % of the
      cumulative variance was explained by a negative loading on very fine sand (0.075
      mm). Individual clusters showed that 43 % of the cumulative variance within
      cluster one could be explained by increased loadings on fine and medium sand
      (0.149-0.250 mm) with a corresponding negative loading on small pebbles (4.75
      mm). An additional 22 % of the cumulative variance was explained by the positive
      loading on coarse sand (0.850 mm). Cluster two was explained by a single factor
      (62 % cumulative variance) highlighting an increased loading on small pebbles and
      coarse sand, and decreased loadings on medium to very fine sand. Principal
      component analysis showed that sediment characterization of the swash zone
      provided the best explanation of between site variance.

PMID- 27695924
TI  - Features of human autologous hamstring graft elongation after pre-tensioning in
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: Precise pre-tensioning protocol of the graft has not been determined in
      anterior cruciate ligament (ACL) reconstruction. The aims of this study are to
      measure the human autologous graft elongation, and to reveal what portion of the
      graft elongated greater after pre-tensioning in ACL reconstruction. METHODS:
      Twenty-four hamstring tendon grafts which were harvested from patients were
      included. A continuous load of 150 N was applied to the graft twice for 30
      seconds each (150 N-1 minute), and the same loading was repeatedly applied (150 N
      2 minute). The amount of elongation of the tendon portion (Length T) and the
      stitched portion (Length S) were measured after each pre-tensioning. RESULTS:
      Length S gradually increased by 1.57 +/- 0.67 mm after the 150 N-1 minute pre
      tensioning and by 2.12 +/- 0.76 mm after the 150 N-2 minute pre-tensioning,
      respectively. Length T was not significantly elongated after 150 N-1 min (p =
      0.66) and 150 N-2 min (p = 0.59). CONCLUSIONS: Graft elongation of the
      approximately 2 mm was observed, particularly in the stitched portion. It is
      necessary for a surgeon to focus on careful removal of slack from each stitch
      during suturing.

PMID- 27695925
TI  - A Randomised Clinical Trial to Compare Coaxial and Noncoaxial Techniques in
      Percutaneous Core Needle Biopsy of Renal Parenchyma.
AB  - PURPOSE: To compare the coaxial and noncoaxial techniques of renal parenchymal
      core needle biopsy. MATERIALS AND METHODS: This is an institutional review board
      approved randomised controlled trial comparing 83 patients (male, n = 49) who
      underwent renal parenchymal core biopsy with coaxial method and 83 patients
      (male, n = 40) with noncoaxial method. The rate of complications, the number of
      glomerular profiles, and the procedural time were evaluated in a comparison of
      the two methods. Correlation between the presence of renal parenchymal disease
      and the rate of complication was also evaluated. RESULTS: The procedural time was
      significantly shorter in the coaxial technique (coaxial group, 5 +/- 1 min;
      noncoaxial group, 14 +/- 2 min; p < 0.001). The rates of complications for the
      coaxial method was significantly lower than the noncoaxial method (coaxial group,
      10.8 %; noncoaxial group, 24.1 %; p = 0.025). There was no significant
      correlation between gender and the rate of complication. The number of glomerular
      profiles was significantly higher in patents who underwent renal biopsy with the
      coaxial method (coaxial group, 18.2 +/- 9.1; noncoaxial group, 8.6 +/- 5.5; p <
      0.001). In the whole study population, the rate of complications was
      significantly higher in patients with a pathologic renal parenchyma compared to
      those with a normal parenchyma (19/71 vs. 10/95; p = 0.006). CONCLUSIONS: Renal
      parenchymal biopsy using a coaxial needle is a faster and safer method with a
      lower rate of complications.

PMID- 27695927
TI  - Erratum to: NK cell-mediated antibody-dependent cellular cytotoxicity is enhanced
      by tamoxifen in HER2/neu non-amplified, but not HER2/neu-amplified, breast cancer
      cells.

PMID- 27695926
TI  - Microstructures of Randall's plaques and their interfaces with calcium oxalate
      monohydrate kidney stones reflect underlying mineral precipitation mechanisms.
AB  - Randall's plaques (RP) are preferred sites for the formation of calcium oxalate
      monohydrate (COM) kidney stones. However, although processes of interstitial
      calcium phosphate (CaP) plaque formation are not well understood, the potential
      of plaque microstructures as indicators of CaP precipitation conditions received
      only limited attention. We investigated RP-associated COM stones for structural
      details of the calcified tissues and microstructural features of plaque-stone
      interfaces as indicators of the initial processes of stone formation.
      Significantly increased CaP supersaturation can be expected for interstitial
      fluid, if reabsorbed ions from the tubular system continuously diffuse into the
      collagenous connective tissue. Densely packed, fine-grained CaP particles were
      found in dense textures of basement membranes while larger, laminated particles
      were scattered in coarse-meshed interstitial tissue, which we propose to be due
      to differential spatial confinements and restrictions of ion diffusion. Particle
      morphologies suggest an initial precipitation as metastable amorphous calcium
      phosphate (ACP). Morphologies and arrangements of first COM crystals at the RP
      stone interface ranged from stacked euhedral platelets to skeletal morphologies
      and even porous, dendritic structures, indicating, in this order, increasing
      levels of COM supersaturation. Furthermore, these first COM crystals were often
      coated with CaP. On this basis, we propose that ions from CaP-supersaturated
      interstitial fluid may diffuse through porous RP into the urine, where a
      resulting local increase in COM supersaturation could trigger crystal nucleation
      and, hence, initiate stone formation. Ion-depleted fluid in persistent pores of
      initial COM layers may get replenished from interstitial fluid, leading to CaP
      precipitation in porous COM.

PMID- 27695929
TI  - The Extent of Surgery for Papillary Thyroid Microcarcinoma: The Controversy
      Continues.

PMID- 27695930
TI  - Do we still need fluoroscopy to perform injections in the musculoskeletal system?

PMID- 27695928
TI  - Age-related changes in force control under different task contexts.
AB  - We investigated age-related differences in motor behavior under different task
      contexts of isometric force control. The tasks involved rapid force production
      and force maintenance, either separately or in combination. For the combined
      context, we used Fitts-like tasks, in which we scaled either the force level (D
      manipulation, i.e., manipulation of the amplitude of the force to be produced) or
      the tolerance range (W manipulation, i.e., manipulation of the target width in
      which force is allowed to fluctuate). We studied two age groups and analyzed
      mainly variables that quantify behavioral variability (SD), information
      processing (signal-to-noise ratio and efficiency functions), and age-related
      slowing (slowing ratio). For rapid force control, age-related differences were
      more pronounced when preplanned processes were primarily involved, that is, in
      the rapid force production and Fitts-D manipulation tasks. Further, older adults
      were comparable to the younger adults in terms of end-point variability at the
      cost of being slower and more variable in timing. For force maintenance control,
      requiring mainly online control, age-related differences were the most visible in
      the stabilized phase of Fitts-D manipulation, followed by Fitts-W manipulation
      for SD, and then the force maintenance task. In sum, our findings reveal an age
      related reorganization of how preplanned and online control processes are
      combined under different force control contexts. Indeed, both behavioral slowing
      and the overreliance on online control processes seem to be dependent on the
      task. In this respect, beyond the study of force control, we show the interest of
      investigating age effects using functionally different tasks.

PMID- 27695931
TI  - Modulation of digestive enzyme activities in the avian digestive tract in
      relation to diet composition and quality.
AB  - In nature, birds are faced with variable food sources that may differ in
      composition (protein vs. carbohydrates) and quality (highly digestible material
      vs. indigestible fiber). Studies in passerine birds and some commercial poultry
      demonstrate that the gastrointestinal tract can respond to varying diet
      composition and quality by changing morphology and/or activities of digestive
      enzymes. However, studies in additional avian species are warranted to understand
      generalities of these trends. We first fed juvenile mallards (Anas
      platyrhynchos), chickens (Gallus gallus), and quails (Coturnix coturnix) on
      either high-carbohydrate or high-protein diets. For the most part, birds fed the
      high-carbohydrate diet had higher small intestinal and cecal disaccharidase
      activities (maltase and sucrase). However, only mallards exhibited higher small
      intestinal aminopeptidase-N (APN) activities when fed the high-protein diet.
      These results differ from passerine birds, which largely modulate small
      intestinal proteases, but not disaccharidases. In another trial, we fed Canada
      geese (Branta canadensis) diets that varied in both their protein and fiber
      concentrations for approximately 3.5 months. Birds fed the high-fiber diets had
      significantly longer small intestines and caeca compared to those fed low-fiber
      diets. Additionally, geese fed the high-fiber diets exhibited lower mass-specific
      activities of small intestinal sucrase, and higher activities of APN when summed
      across the small intestine and ceca. Similar to the avian species above, geese
      fed the high-protein diets did not exhibit flexibility in their small intestinal
      APN activities. Overall, these experiments demonstrate that responsiveness of the
      avian digestive tract to diet composition may have phylogenetic or ecological
      constraints. Studies on other avian taxa are needed to understand these patterns.

PMID- 27695933
TI  - Evidence-based medicine in plastic surgery.

PMID- 27695932
TI  - The significance of extramural venous invasion in R1 positive rectal cancer.
AB  - BACKGROUND AND AIMS: Evidence has shown that a positive resection margin (R1) is
      a key determinant of subsequent local recurrence and a poor prognostic factor in
      rectal cancer. The aim of this study was to evaluate the outcomes and
      prognosticators in patients with R1 resection of rectal cancer. MATERIAL AND
      METHODS: Retrospective study of all patients operatively managed within our
      institution between April 2008 and April 2013 for rectal cancer. Baseline
      demographics and multiple outcome measures recorded. Overall survival (OS),
      disease-free survival (DFS) and recurrence were the primary outcome measures.
      RESULTS: Overall, there were 306 primary rectal cancers. Seventy-six percent were
      grade T3/4 tumours. OS was 30 months. R1 rate was 16 % (48 patients). Thirty-one
      patients underwent APR and 17 AR. In patients who responded to neoadjuvant
      chemotherapy (NAC), overall survival was 55 months, with no extramural venous
      invasion (EMV) seen in this cohort. In non-responders OS was 29 months, with EMV
      in 48 %. In patients who did not receive NAC, OS was 23 months, with EMV in 74 %.
      EMV is a strong predictor for poor survival following R1 (p = 0.001). We also
      found a correlation between number of positive nodes and OS/DFS (p = 0.004).
      CONCLUSIONS: In this small cohort of patients with R1 positive rectal cancers,
      response to NAC is the strongest predictor of poor overall and disease-free
      survival. In patients who respond to NAC, OS and DFS has been shown to be
      positive, with a reduced rate of EMV.

PMID- 27695934
TI  - The development of an ICF-based clinical guideline and screening tool for the
      standardized assessment and evaluation of functioning after head and neck cancer
      treatment.
AB  - The assessment and evaluation of functioning and quality of life after tumor
      treatment in head and neck cancer (HNC) are considered as essential aspects of
      clinical routine and studies. A huge number of instruments are available that
      have been designed to evaluate functioning and quality of life after HNC
      treatment. The diversity of these instruments in terms of content, response
      options and administration hinders the comparability of available studies and the
      performance of meta-analyses. The objective of this paper is to inform about the
      development of a screening tool for the standardized assessment and evaluation of
      functioning based on the International Classification of Functioning, Disability
      and Health (ICF) Core Set for HNC. We followed a multi-step approach including
      (1) preparatory studies to identify and preselect suitable instruments for the
      assessment of functioning, (2) a decision-making process to agree on an ICF-based
      clinical guideline including instruments assessing functioning and (3) the
      development of a computer-based standardized screening tool to assess and
      evaluate functioning based on this guideline in clinical routine. Twenty-one
      experts participated in a consensus meeting and decided on instruments to be
      included in an ICF-based clinical guideline and screening tool for the assessment
      and evaluation of functioning in HNC patients in cancer treatment. The chosen
      instruments cover all aspects of the ICF Core Set for HNC addressing therapy
      control, pain, food intake/swallowing, voice/speech/breathing, other somatic
      complaints and psychosocial aspects. The screening tool contains patient-reported
      outcome measures and a clinician's checklist. It has to be further tested in
      clinical practice.

PMID- 27695936
TI  - [Settings-based prevention of overweight in childhood and adolescents :
      Theoretical foundation, determinants and intervention planning].
AB  - BACKGROUND: Childhood and adolescent overweight can still be seen as a global
      public health problem. Based on our socioeconomic understanding, overweight is
      the result of a complex interplay of a diverse array of factors acting on
      different levels. Hence, in addition to individual level determinants overweight
      prevention should also address environmental related factors as part of a
      holistic and integrated setting approach. OBJECTIVE: This paper aims to discuss
      the setting approach with regard to overweight prevention in childhood and
      adolescence. In addition to a summary of environmental factors and their
      empirical influence on the determinants of overweight, theoretical approaches and
      planning models of settings-based overweight prevention are discussed. RESULTS:
      While settings can be characterized as specific social-spatial subsystems (e. g.
      kindergarten, schools), living environments relate to complex subject-oriented
      environments that may include various subsystems. Direct social contexts,
      educational contexts and community contexts as relevant systems for young people
      contain different evidence-based influences that need to be taken into account in
      settings based overweight prevention. To support a theory-driven intervention,
      numerous planning models exist, which are presented here. DISCUSSION: Given the
      strengthening of environments for health within the prevention law, the
      underlying settings approach also needs further development with regard to
      overweigth prevention. This includes the improvement of the theoretical
      foundation by aligning intervention practice of planning models, which also has a
      positive influence on the ability to measure its success.

PMID- 27695935
TI  - Clinical response in a risperidone-medicated naturalistic sample: patients'
      characteristics and dose-dependent pharmacokinetic patterns.
AB  - The purpose of this study was to disentangle an association between plasma
      concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone
      (9-OH-RIS) and the active moiety, AM (RIS + 9-OH-RIS), and clinical response in a
      naturalistic sample. Plasma concentrations of RIS, 9-OH-RIS and AM in patients
      out of a therapeutic drug monitoring (TDM) database were compared between
      responders (n = 64) and non-responders (n = 526) using the Clinical Global
      Impressions (CGI) Scale. Daily dosage of risperidone did not differ between
      responders and non-responders. Differences for active moiety plasma levels
      between the two groups did not reach statistical significance. However,
      responders showed lower plasma concentrations of the parent compound RIS as well
      as lower metabolic ratios RIS/9-OH-RIS than non-responders (p = 0.017 and p =
      0.034). These differences did not remain after controlling for age and baseline
      symptoms. Furthermore, the cohort was split into two subgroups based on the daily
      dosage: patients under high (>=6 mg/day) (R H, n = 187) and patients under lower
      dosages (<6 mg) (R L, n = 403) of risperidone. Differences between responders and
      non-responders after controlling for demographic and clinical characteristics
      remained only for plasma concentrations of active moiety in the lower-dose
      medicated groups; non-responders showed higher active moiety plasma
      concentrations than responders. Understanding the mechanisms involved and factors
      associated with the clinical response in patients medicated with antipsychotics
      is of great interest. Our data imply that clinical response to an antipsychotic
      treatment cannot be attributed to a single pharmacokinetic pattern. It seems to
      be rather a complex patchwork of influencing factors such as demographic and
      clinical characteristics as well as the metabolizer status as surrogate of CYP
      activity. It seems that the ratio between RIS and 9-OH-RIS may play a crucial
      role in mediating the clinical effect.

PMID- 27695937
TI  - [Influenza and community acquired pneumonia in German primary care].
AB  - Influenza and community-acquired pneumonia (CAP) impose a considerable annual
      burden on the German primary care system. Yet there is a lack of epidemiological
      data from the country's outpatient sector on groups at risk as well as on the
      complications of these diseases.The Robert Koch Institute (RKI) initiated the
      study to identify population groups at increased risk for influenza or CAP as
      well as related comorbidities and sequelae. We present the methodology of the
      study and the descriptive analysis of the patients.ICD-10-based data was
      collected in 89 primary health care practices between January 2012 and April 2015
      using a data extraction tool developed on behalf of the RKI. Case-based
      anonymized information was recorded for all patients in whom influenza, CAP or
      other acute respiratory infections (ARI) were diagnosed. For each patient
      information on all diagnoses including the date were retrospectively and
      prospectively collected (each for six months) as well as age, sex and influenza
      vaccination.Data on 156,803 patients with ARI was collected, of them 7909
      patients with influenza (within influenza waves) and 8528 patients with CAP
      diagnoses. Influenza diagnoses showed a strong seasonal pattern and captured
      annual influenza waves in Germany. Of the influenza cases 1.6 % had a following
      diagnosis of CAP within 30 days. Age-specific prevalence of chronic diseases such
      as asthma and diabetes was significantly higher in the study population as
      compared to the German population.The developed tool delivers in a standardized
      fashion ICD-10-coded epidemiological data on population-based burden of influenza
      and CAP in Germany. As the descriptive analysis showed, the collected dataset is
      a reliable and solid basis for the further investigations of the study questions.

PMID- 27695938
TI  - [Social counseling in outpatient cancer counseling centers : Offers and use by
      advice-seekers].
AB  - BACKGROUND: Outpatient psychosocial cancer care has gained importance in recent
      years and psychosocial counselling services (PCS) offer a broad spectrum of
      counselling interventions. Yet there is no published research on PCS legal
      counselling services. This study investigated the range of issues addressed by
      legal counselling and their relationship with characteristics of advice seekers
      and counsellors. METHODS: We analyzed the records of 21 PCS funded by the German
      Cancer Aid (DKH) including 5203 advice seekers (80 % patients, 20 % others
      including friends and family; age ? 54 years; 24 % male) in 20,947 counselling
      sessions. We calculated descriptive statistics and binary logistic regression
      analyses (legal counselling: yes/no). RESULTS: Fifty-five percent of counselling
      seekers received legal counselling and 28 % approached the PCS exclusively for
      legal counselling. The proportion of people seeking legal advice ranged from 15
      to 87 % between counselling centers. The most common topics during legal
      counselling were medical rehabilitation programs (57 %) and disability law (43
      %). Counselling occurred in a single session in 68 % of cases and was mostly
      sought by older and unemployed persons with a recent diagnosis. Legal counselling
      made up 18 % of counselling time. Legal advice was mostly given by social workers
      (71 %). CONCLUSIONS: Legal counselling is a major part of psychosocial care
      services. Our results reveal large differences between counselling centers.
      Further research on quality of care and efficacy of legal counseling is needed.

PMID- 27695939
TI  - [What are the determinants of childhood obesity? : A literature review as part of
      the project "Nationwide Monitoring of Childhood Obesity Determinants"].
AB  - BACKGROUND: Obesity can impair health even in childhood and unfold negative
      health consequences through an individual's lifespan. In Germany, to date, a
      systematic and periodically updated synopsis of the multifaceted determinants of
      childhood obesity is lacking. In this paper, we present the results of a
      systematic literature review on childhood obesity determinants, which was
      conducted over the course of the implementation of nationwide monitoring.
      METHODS: The review was carried out in three steps. Initially, a search for
      etiological models of childhood obesity was conducted. Based on these results, a
      systematic review of reviews on childhood obesity determinants was carried out.
      Finally, the results were verified by taking international guidelines on
      childhood obesity into account. RESULTS: In total, 21 etiological models, 75
      reviews and 7 guidelines were identified. Over 60 determinants were extracted
      from these publications and were summarized into the following categories:
      nutritional behavior, physical activity behavior, sleeping pattern, biological
      determinants and diseases, prenatal and early childhood determinants, psycho
      social determinants, food environment, moveability/walkability, setting and
      social environment, health promotion and prevention, socioeconomic, demographic,
      and sociocultural determinants. CONCLUSION: This review demonstrates the complex
      patterns of childhood obesity determinants in correspondence with a socio
      ecological approach. The review will form the basis for the monitoring-system
      "Nationwide Monitoring of Childhood Obesity Determinants", which will be
      implemented at the Robert Koch Institute by the end of 2017.

PMID- 27695940
TI  - Immunohistochemical and electronmicroscopic features of mesenchymal-to-epithelial
      transition in human developing, postnatal and nephrotic podocytes.
AB  - Differentiation of human podocytes starts with mesenchymal-to-epithelial
      transition (MET) of the metanephric mesenchyme into the S-shaped nephrons. During
      further development, differentiating podocytes regain mesenchyme-like cell
      characteristics by epithelial-to-mesenchymal transition (EMT), leading to
      formation of the terminally differentiated, non-dividing cell. Both MET and EMT
      processes involve changes in content and organization of cytoskeletal and actin
      filaments, accompanied by the increased glomerular vascularization. Here, we
      analyze and compare normal human developing, postnatal and nephrotic podocytes
      and glomeruli, using immunohistochemical and double immunofluorescent methods for
      detection of markers of cytoskeletal filaments (nestin, cytokeratin 10-CK10,
      vimentin and alpha-SMA), vasculogenesis (CD31 and VEGF) and podocyte function
      (receptor for advanced glycation end products, RAGE). In addition, electron
      microscopy is used to detect ultrastructural changes of the podocytes. Early
      metanephric cup mesenchyme expresses all investigated markers except alpha-SMA,
      which characterizes only surface mesenchymal cells. In differentiating podocytes
      and cells of Bowman's capsule (parietal podocytes) nestin decreases, vimentin
      increases, while CK10 gradually disappears. Increase in alpha-SMA is associated
      with blood vessels development, appearance of podocyte pedicles and slit
      diaphragm and loss of intercellular connections (zonulae adherentes). Increase in
      CD31 characterizes vascular glomerular tufts development, while decrease in RAGE
      expression accompanies normal podocyte differentiation. In congenital nephrotic
      syndrome of the Finnish type, dedifferentiated podocytes display changes in
      cytoskeletal filaments and depletion of podocyte pedicles, while glomerular
      vascular supply is diminished. Our data also suggest high potential of
      metanephric mesenchyme and parietal podocytes in possible regeneration of the
      damaged podocytes.

PMID- 27695941
TI  - Mortality-related risk factors and long-term survival after 4460 liver resections
      in Sweden-a population-based study.
AB  - PURPOSE: The objectives of this study were to analyze the outcome after
      hepatectomy and to identify contributing factors to mortality and long-term
      survival in a population-based setting. METHOD: A retrospective, nationwide
      register study was performed. All patients who underwent hepatectomy in Sweden
      between 2002 and 2011 were identified in the Swedish Hospital Discharge Registry
      using their unique personal identification numbers. This cohort was linked to the
      National Cancer Registry (cancer diagnosis), the National Registry of Causes of
      Death, and the Migration Registry. Survival analysis by Kaplan-Meier method was
      performed to assess long-term outcome. A Cox regression model was used to analyze
      risk factors affecting long-term survival. RESULTS: Overall, 4460 hepatectomies
      were performed. The 30- and 90-day mortalities were 1.8 and 3.1 %, respectively.
      The overall 5- and 10-year survival rates for all diagnoses were 45 and 38 %,
      respectively. Independent risk factors for 5-year mortality were as follows:
      patient age, comorbidity, male gender, intrahepatic/extrahepatic
      cholangiocarcinoma, gallbladder cancer, extent of hepatectomy, and hepatectomies
      performed at non-university hospitals. Re-resection (78.1 % with diagnosis
      "metastasis") was performed on 374 patients. In these patients, mortality risk
      decreased by >50 % (HR 0.42; 95 %, CI 0.33-0.53). CONCLUSION: In a population
      based analysis, liver resections are done with a low mortality risk and good long
      term outcome. Patients who underwent resection at a University Hospital showed a
      significant better outcome compared to patients resected at non-University
      Hospitals. These results support further centralization of liver surgery. Re
      resection should be performed if feasible.

PMID- 27695942
TI  - The development of anatomy: from macroscopic body dissections to stem cell
      derived organoids.
AB  - Anatomy as a descriptive topic of research and instruction in medicine has been
      increasingly influenced by discoveries in molecular cell and developmental
      biology and most recently the advent of human induced pluripotent stem cells and
      organoids. We summarize here how anatomy has been influenced by developmental and
      stem cell biologists, and how in vitro modelling of the three-dimensional body
      environment is emerging to understand structure and function of cells during
      differentiation processes in development and disease.

PMID- 27695945
TI  - Nominee and nominator, but never Nobel Laureate: Vincenz Czerny and the Nobel
      Prize.
AB  - PURPOSE: The Heidelberg surgeon Vincenz Czerny (1842-1916) is remembered as
      pioneer of innovative operations as well as entrepreneur of interdisciplinary
      cancer therapy. The purpose of this paper is to describe his role during the
      early history of the Nobel Prize in physiology or medicine. METHOD: Based on
      documents from the Nobel Archive, this paper investigates how Czerny contributed,
      both as nominee and nominator, in shaping the early years of Nobel Prize history.
      RESULTS: Vincenz Czerny was nominated at least three times for the Nobel Prize,
      but he was never selected. Czerny's own nomination letters pinpoint important
      trends in medicine around the turn of the century. At least seven of the
      candidates he put forward, became Nobel Laureates. CONCLUSION: Czerny-like many
      other internationally renowned surgeons during the first decades of the twentieth
      century-missed out on the Nobel Prize, partly because it is not a lifetime award
      and his work would have to have been more recent. However, with his nominations,
      Czerny helped to shape the Nobel Prize to become the most important scientific
      award worldwide.

PMID- 27695944
TI  - Endoscopic and clinical benefits of hyaluronic acid in children with chronic
      adenoiditis and middle ear disease.
AB  - Hyaluronic acid (HA) is involved in modulating inflammatory airway processes and
      mucociliary clearance. Some studies have tested the effectiveness of the topical
      administration of HA in patients with upper airway diseases with positive
      preliminary results. A prospective, single-blind, 1:1 randomised controlled study
      was performed to assess the efficacy and safety of the daily topical
      administration of 9 mg of sodium hyaluronate in 3 mL of a 0.9 % sodium saline
      solution on the basis of endoscopic and clinical parameters in children with
      chronic adenoiditis associated with recurrent acute otitis media and otitis media
      with effusion; age- and gender-matched children receiving normal 0.9 % sodium
      chloride saline solution were used as controls. Analysis was based on 103 (mean
      age 63.3 +/- 18.2 months; 52 males, 50.5 %) children: 54 in the study group and
      49 in the control group. A statistically significant reduction in the mean number
      of all acute otitis media episodes (AOME) (mean reduction 0.8 +/- 0.4 per month;
      p value 0.05) and AOME without tympanic membrane perforation (mean reduction 0.6
      +/- 0.3 per month; p value 0.04) after recruitment was documented only in the
      study group. HA significantly improved all the endoscopic outcomes (p values
      ranging between 0.05 and <0.01) but one. Nasal washing with saline solution was
      effective on only three of them (p values ranging between 0.03 and <0.01). No
      untoward effects were documented. Our results confirm the safety and document the
      positive effect of topically administered HA solution on children with chronic
      adenoiditis associated with middle ear disease.

PMID- 27695943
TI  - The role of CEA-related cell adhesion molecule-1 (CEACAM1) in vascular
      homeostasis.
AB  - Carcinoembryonic antigen (CEA)-related cell adhesion molecules belong to the
      immunoglobulin superfamily, are expressed in a broad spectrum of tissues and cell
      types and exert context-dependent activating as well as inhibitory effects. Among
      these molecules, the CEA-related cell adhesion molecule-1 (CEACAM1) is a
      transmembrane molecule with an extracellular, a transmembrane and a cytoplasmic
      domain. The latter contains immunoreceptor tyrosine-based inhibitory motifs and
      functions as a signaling molecule. CEACAM1 can form homo- and heterodimers which
      is relevant for its signaling activities. CEACAM1 acts as co-receptor that
      modulates the activity of different receptor types including VEGFR-2, and B and T
      cell receptors. CEACAM1 is expressed in endothelial cells, in pericytes of
      developing and newly formed immature blood vessels and in angiogenically
      activated adult vessels, e.g., tumor blood vessels. However, it is either
      undetectable or only weakly expressed in quiescent blood vessels. Recent studies
      indicated that CEACAM1 is involved in the regulation of the endothelial barrier
      function. In CEACAM1 -/- mice, increased vascular permeability and development of
      small atherosclerotic lesions was observed in the aortae. CEACAM1 is also
      detectable in activated lymphatic endothelial cells and plays a role in tumor
      lymphangiogenesis. This review summarizes the vascular effects of CEACAM1 and
      focuses on its role in vascular morphogenesis and endothelial barrier regulation.

PMID- 27695946
TI  - Browning of subcutaneous fat and higher surface temperature in response to
      phenotype selection for advanced endurance exercise performance in male DUhTP
      mice.
AB  - For the assessment of genetic or conditional factors of fat cell browning, novel
      and polygenic animal models are required. Therefore, the long-term selected
      polygenic mouse line DUhTP originally established in Dummerstorf for high
      treadmill performance is used. DUhTP mice are characterized by increased fat
      accumulation in the sedentary condition and elevated fat mobilization during mild
      voluntary physical activity. In the present study, the phenotype of fat cell
      browning of subcutaneous fat and a potential effect on oral glucose tolerance, an
      indicator of metabolic health, were addressed in DUhTP mice. Analysis of
      peripheral fat pads revealed increased brite (brown-in-white) subcutaneous
      adipose tissues and in subcutaneous fat from DUhTP mice higher levels of irisin
      and different markers of fat cell browning like T-box transcription factor
      (Tbx1), PPARalpha, and uncoupling protein (UCP1) (P < 0.05) when compared to
      unselected controls. UCP1 was further increased in subcutaneous fat from DUhTP
      mice in response to mild exercise (fourfold, P < 0.05). In addition, surface
      temperature of DUhTP mice was increased when compared to controls indicating a
      physiological effect of increased UCP1 expression. The present study suggests
      that DUhTP mice exhibit different markers of mitochondrial biogenesis and fat
      browning without external stimuli. At an age of 43 days, sedentary DUhTP mice
      have improved metabolic health as judged from lower levels of blood glucose after
      an oral glucose tolerance test. Consequently, the non-inbred mouse model DUhTP
      represents a novel model for the identification of fat cell browning mechanisms
      in white adipose tissues.

PMID- 27695947
TI  - L1CAM: amending the "low-risk" category in endometrial carcinoma.
AB  - PURPOSE: Low- and intermediate-risk endometrial carcinomas have an excellent
      prognosis. Nonetheless, a small subgroup of such patients will experience
      unexpected relapse. Recently L1CAM was suggested to be a strong prognosticator in
      endometrial carcinoma. The focus of our study was on low- and intermediate-risk
      disease, where no or only limited adjuvant treatment is recommended according to
      current guidelines. METHODS: Endometrial carcinomas of low, intermediate and high
      intermediate risk according to published 2016 consensus guidelines were
      identified. The study was limited to cases with previous central pathology review
      focusing on histotype, depth of myometrial invasion, presence of lymphovascular
      space invasion (LVSI) and MELF pattern of invasion. Standard L1CAM
      immunohistochemistry was performed. Disease-specific uni- and multivariate
      survival analyses were calculated. RESULTS: A total of 344 cases were available
      for immunohistochemistry (low-risk: n = 250; intermediate-risk: n = 67; high
      intermediate-risk: n = 27). L1CAM positivity rates were: 29/344 (8.4 %; all
      cases), 18/250 (7.2 %; low-risk), 6/67 (9.0 %; intermediate-risk) and 5/27 (18.5
      %; high-intermediate-risk). Expression of L1CAM was independent of LVSI and MELF.
      L1CAM was a significant independent prognosticator for disease-specific survival
      with a hazard ratio of 5.98 [CI 1.50-22.14, p = 0.012]. Adverse prognostic
      significance of L1CAM positivity was maintained after low-risk subgroup analysis
      (5-year disease-specific survival rates 71.8 vs. 100 %, p < 0.0001). All four
      tumour-related deaths in the subgroup of low-risk disease occurred in patients
      with L1CAM-positive tumours. CONCLUSION: The current definition of "low-risk" in
      endometrial carcinoma should be amended. "Low-risk carcinomas" should be limited
      to L1CAM-negative tumours. L1CAM status will play a key role in future algorithms
      to tailor adjuvant treatment and patient follow-up strategies.

PMID- 27695948
TI  - Occult shunt infections-think of biofilms.

PMID- 27695949
TI  - Natural structural diversity within a conserved cyclic peptide scaffold.
AB  - We recently isolated and described the evolutionary origin of a diverse class of
      small single-disulfide bonded peptides derived from Preproalbumin with SFTI-1
      (PawS1) proteins in the seeds of flowering plants (Asteraceae). The founding
      member of the PawS derived peptide (PDP) family is the potent trypsin inhibitor
      SFTI-1 (sunflower trypsin inhibitor-1) from Helianthus annuus, the common
      sunflower. Here we provide additional structures and describe the structural
      diversity of this new class of small peptides, derived from solution NMR studies,
      in detail. We show that although most have a similar backbone framework with a
      single disulfide bond and in many cases a head-to-tail cyclized backbone, they
      all have their own characteristics in terms of projections of side-chains,
      flexibility and physiochemical properties, attributed to the variety of their
      sequences. Small cyclic and constrained peptides are popular as drug scaffolds in
      the pharmaceutical industry and our data highlight how amino acid side-chains can
      fine-tune conformations in these promising peptides.

PMID- 27695950
TI  - Rescue of recombinant Newcastle disease virus: current cloning strategies and RNA
      polymerase provision systems.
AB  - Since the first rescue of a recombinant Newcastle disease virus (rNDV) in the
      late 1990s, many more rNDVs have been rescued by researchers around the world.
      Regardless of methodology, the main principle behind rescue of the virus has
      remained the same, i.e., the formation of a functional replication complex by
      simultaneously providing the full-length viral RNA and the viral NP, P and L
      proteins. However, different strategies have been reported for the insertion of
      the full-length genome into a suitable transcription vector, which remains the
      most challenging step of the rescue. Moreover, several systems have been
      published for provision of the DNA-dependent RNA polymerase, which is needed for
      transcription of viral RNA (vRNA) from the transfected plasmid DNA. The aim of
      this article is to consolidate all of the current cDNA assembly strategies and
      transcription systems used in rescue of rNDV in order to attain a better
      understanding of the advantages and disadvantages of each approach.

PMID- 27695951
TI  - Monitoring of influenza A viruses in wild bird populations in Kazakhstan in 2002
      2009.
AB  - A comprehensive influenza virus monitoring study of wild birds was carried out at
      important flyway resting places and wintering sites in Kazakhstan over eight
      years. More than 3200 birds belonging to 155 species were sampled. Nearly three
      fourths of the birds belonged to the orders Anseriformes and Charadriiformes. In
      total, 118 hemagglutinating agents were isolated, and 95 of them were identified
      as influenza A viruses. The influenza viruses comprised eight different subtypes
      with a high prevalence of H13 and H3 viruses and also included low-pathogenic H5
      viruses. The vast majority of the H13 viruses were isolated from members of the
      family Laridae, whereas the H3 viruses mostly originated from members of the
      family Anatidae, both in concordance with other monitoring studies. All virus
      isolates were recovered from cloacal swabs or fecal samples only. The influenza
      viruses were identified mainly in wetlands north of the Caspian Sea. These
      findings should be integrated in the design of further wild-bird-monitoring
      activities.

PMID- 27695953
TI  - "Incidentalomas" on abdominal and pelvic CT in emergency radiology: literature
      review and current management recommendations.
AB  - The purpose of this article is to familiarize radiologists and clinicians with a
      subset of common and uncommon incidental findings on abdominal and pelvic
      computed tomography examinations, including hepatic, splenic, renal, adrenal,
      pancreatic, aortic/iliac arterial, gynecological, and a few other miscellaneous
      findings, with an emphasis on "incidentalomas" discovered in the emergency
      setting. In addition, we will review the complex problem of diagnosing such
      entities, and provide current management recommendations. Representative case
      examples, which we have encountered in our clinical practices, will be
      demonstrated.

PMID- 27695952
TI  - Multimodality imaging of placental masses: a pictorial review.
AB  - Placental masses are uncommonly identified at the time of obstetric ultrasound
      evaluation. Understanding the pathologies presenting as placental masses is key
      for providing a differential diagnosis and guiding subsequent management, which
      may include additional imaging with magnetic resonance (MR) imaging. Potential
      benign entities include chorioangiomas and teratomas. Larger chorioangiomas can
      cause fetal cardiovascular issues from volume overload. Placental mesenchymal
      dysplasia has an association with fetal anomalies and detailed fetal evaluation
      should be performed when it is suspected. Identifying other cystic masses such as
      partial and complete moles is crucial to prevent erroneous pregnancy termination.
      This review addresses normal imaging appearance of the placenta on ultrasound and
      MR imaging and describes various trophoblastic and nontrophoblastic placental
      masses. Potential placental mass mimics including uterine contractions and
      thrombo-hematomas are also presented.

PMID- 27695954
TI  - Can psychiatric childhood disorders be due to inborn errors of metabolism?
AB  - Many patients who visit a centre for hereditary metabolic diseases remarkably
      also suffer from a child psychiatric disorder. Those child psychiatric disorders
      may be the first sign or manifestation of an underlying metabolic disorder. Lack
      of knowledge of metabolic disorders in child psychiatry may lead to diagnoses
      being missed. Patients therefore are also at risk for not accessing efficacious
      treatment and proper counselling. To search the literature for the co-occurrence
      of child psychiatric disorders, such as ADHD, autism, psychosis, learning
      disorders and eating disorders and metabolic disorders. A search of the
      literature was conducted by performing a broad search on PubMed, using the terms
      "ADHD and metabolic disorders", "autism and metabolic disorders", "psychosis and
      metabolic disorders", "learning disorders and metabolic disorders", and "eating
      disorders and metabolic disorders". Based on inclusion criteria (concerning a
      clear psychiatric disorder and concerning a metabolic disorder) 4441 titles and
      249 abstracts were screened and resulted in 71 relevant articles. This thorough
      literature search provides child and adolescent psychiatrists with an overview of
      metabolic disorders associated with child psychiatric symptoms, their main
      characteristics and recommendations for further investigations.

PMID- 27695955
TI  - Light-curing units used in dentistry: factors associated with heat development
      potential risk for patients.
AB  - OBJECTIVES: To investigate how heat development in the pulp chamber and coronal
      surface of natural teeth with and without cusps subjected to irradiance using
      light-emitting diode (LED)-light-curing units (LCUs) is associated with (i)
      irradiance, (ii) time, (iii) distance, and (iv) radiant exposure. MATERIALS AND
      METHODS: Three different LED-LCUs were used. Their irradiance was measured with a
      calibrated spectrometer (BlueLight Analytics Inc., Halifax, Canada). An
      experimental rig was constructed to control the thermal environment of the teeth.
      The LED-LCU tip position was accurately controlled by a gantry system. Tooth
      surface temperature was measured by thermography (ThermaCAM S65 HS, FLIR Systems,
      Wilsonville, USA) and pulp chamber temperature with a thermocouple. LED-LCU tip
      distance and irradiation times tested were 0, 2, and 4 mm and 10, 20, and 30 s,
      respectively. Ethical permission was not required for the use of extracted teeth.
      RESULTS: Maximum surface and pulp chamber temperatures were recorded in tooth
      without cusps (58.1  degrees C  +/- 0.9  degrees C and 43.1  degrees C +/- 0.9 
      degrees C, respectively). Radiant exposure explained the largest amount of
      variance in temperature, being more affected by time than irradiance.
      CONCLUSIONS: At all combinations of variables tested, repeated measurements
      produced consistent results indicating the reliability of the method used.
      Increased exposure time seems to be the factor most likely to cause tissue
      damage. CLINICAL RELEVANCE: Risk of superficial tissue damage at irradiances
      >1200 mW/cm2 is evident. There is a risk of pulp damage when only thin dentin is
      left at higher irradiances (>1200 mW/cm2). Clinicians should be aware of LED-LCU
      settings and possible high temperature generated.

PMID- 27695957
TI  - Humoral immune responses and viral shedding following vaccination with modified
      live porcine reproductive and respiratory syndrome virus vaccines.
AB  - The antibody response and pattern of shedding of vaccine virus following
      vaccination with modified live genotype I or II porcine reproductive and
      respiratory syndrome virus (PRRSV) vaccines (MLVs) were investigated. Ninety
      PRRSV-free pigs were divided randomly seven, groups including the NEG, EU1, EU2,
      US1, US2, US3 and US4 groups. The NEG group was unvaccinated. The EU1, EU2, US1,
      US2, US3 and US4 groups were vaccinated with the following MLVs: AMERVAC(r) PRRS,
      Porcillis(r) PRRS, FosteraTM PRRS, Ingelvac(r) PRRS MLV, Ingelvac(r) PRRS ATP,
      and PrimePacTM PRRS+ , respectively. Sera were quantitatively assayed for viral
      RNA using qPCR. Antibody responses were measured using Idexx ELISA and serum
      neutralization (SN). Shedding of vaccine virus was investigated using sentinel
      pigs and by detection of viral RNA in tonsil scrapings. Antibody responses were
      detected by ELISA at 7-14 days post-vaccination (DPV) and persisted at high
      titers until 84 DPV in all MLV groups. The SN titers were delayed and isolate
      specific. SN titers were higher for the homologous virus than for heterologous
      viruses. Age-matched sentinel pigs introduced into the EU2, US2 and US3 groups at
      60 DPV seroconverted. In contrast, sentinel pigs introduced at 84 DPV remained
      negative in all of the MLV groups. Vaccine viral RNA was detected in tonsil
      scrapings from the EU2, US2 and US3 groups at 84-90 DPV. No viral RNA was
      detected beyond 70 DPV in the EU1, US1 and US4 groups. In conclusion, all MLV
      genotypes induced rapid antibody responses, which were measured using ELISA. The
      development of SN antibodies was delayed and isolate-specific. However, the
      shedding pattern was variable and depended on the by virus isolate used to
      manufacture the vaccine.

PMID- 27695958
TI  - Dengue scenario: Chennai perspective-a six-year study (2009-2014).
AB  - Dengue is a public health problem with an increasing global incidence and
      geographic distribution in almost all tropical and subtropical countries, with a
      transition from epidemic to endemic occurrence. In this study, we report a six
      year analysis (2009-2014) performed at the Department of Virology, King Institute
      of Preventive Medicine, Chennai, Tamil Nadu, India. Our data confirm earlier
      findings that dengue is highly endemic in Chennai. In the present study, 10,099
      serum samples from suspected dengue cases were tested for IgM ELISA (NIV Capture)
      and IgG Panbio ELISA (Australia). Of these suspected cases 6,798 and 3,301 were
      pediatric and adult cases, respectively, and 1,927 (19.08 %) were confirmed
      serologically as dengue. Of these, 1,752 (25.7 %) and 175 (5.3 %) were pediatric
      and adult cases, respectively. The aim of this study was to highlight the
      occurrence of DHF and DSS, mainly among the pediatric population, in which the
      infection causes higher mortality and morbidity. The overall positivity was
      higher in the pediatric group than in the adults. Detection of both IgM and IgG
      positivity will be useful for monitoring infection rates, the disease spectrum,
      and the prevalence of the different serotypes, which will give us insight about
      the circulating serotypes and pathogenicity. These data will be valuable for
      providing an early warning to predict an impending epidemic leading to major
      clinical manifestations of DHF and DSS.

PMID- 27695956
TI  - Octreotide ameliorates inflammation and apoptosis in acute and kindled murine PTZ
      paradigms.
AB  - In the present study, the role of octreotide (OCT) in pentylenetetrazole (PTZ)
      kindling as well as in acute convulsion models was evaluated. Mice were allocated
      in groups as (1) control saline; (2) acute PTZ (PTZ-a; 60 mg/kg, i.p.), as a
      single convulsive dose; and (3) kindled (PTZ-k) receiving nine subconvulsive
      doses of PTZ (40 mg/kg, i.p.) for 17 days. Groups 4-7 received either valproic
      acid (VPA) 50 mg/kg or OCT (50 MUg/kg, Sandostatin(r)) 30 min by oral gavage
      before PTZ-a or PTZ-k. The median seizure stage, latency onset of first stage 4/5
      seizures, and incidence of convulsing animals were recorded. Cortical dopamine
      (DA), tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, caspase (Casp)-3,
      myeloperoxidase (MPO), and nitric oxide (NO) were assessed in addition to
      inducible nitric oxide synthase (iNOS) that was evaluated immunohistochemically
      in a different set of groups. OCT halted PTZ-induced epilepsy delaying convulsion
      latency via modulating MPO and TNF-alpha and normalizing IL-10 with both
      treatment regimens. In PTZ-k, it decreased Casp-3 activity, NO level, and iNOS
      immunoreactivity. OCT in both paradigms decreased DA concentration. The current
      investigation implicates a crucial role for OCT in modulating PTZ-induced
      kindling by regulating inflammatory and apoptotic effects.

PMID- 27695959
TI  - Transanal total mesorectal excision: dissection tips using 'O's and 'triangles'.
AB  - PURPOSE: Transanal total mesorectal excision (taTME) requires specific technical
      expertise, as it is often difficult to ascertain the correct dissection plane.
      Consequently, one can easily enter an incorrect plane, potentially resulting in
      bleeding (sidewall or presacral vessels), autonomic nerve injury and urethral
      injury. We aim to demonstrate specific visual features, which may be encountered
      during surgery and can guide the surgeon to perform the dissection in the correct
      plane. METHOD: Specific features of dissection in the correct and incorrect
      planes are demonstrated in the accompanying video. RESULTS: The 'triangles'
      created using appropriate traction can aid in performing a precise dissection in
      the correct plane. Recognition of features described as 'O's can alert surgeons
      that they are entering a new fascial plane and can avoid incursion into an
      incorrect plane. CONCLUSION: Understanding and recognizing the described features
      which can be encountered in taTME surgery, a safe and accurate TME dissection can
      be facilitated.

PMID- 27695960
TI  - Mortality from solid cancers other than lung, liver, and bone in relation to
      external dose among plutonium and non-plutonium workers in the Mayak Worker
      Cohort.
AB  - Exposure to ionizing radiation has well-documented long-term effects on cancer
      rates and other health outcomes in humans. While in vitro experimental studies
      had demonstrated that the nature of some radiation effects depend on both total
      dose of the radiation and the dose rate (i.e., the pattern of dose distribution
      over time), the question of whether or not the carcinogenic effect of radiation
      exposure depends on the dose rate remains unanswered. Another issue of interest
      concerns whether or not concomitant exposure to external gamma rays and inhaled
      plutonium aerosols has any effect on the external exposure effects. The analyses
      of the present paper focus on the risk of solid cancers at sites other than lung,
      liver, and bone in Mayak workers. Recent findings are reviewed indicating that
      there is no evidence of plutonium dose response for these cancers in the Mayak
      worker cohort. Then the evidence for differences in the external dose effects
      among workers with and without the potential for exposure to alpha particles from
      inhaled plutonium is examined. It is found that there is no evidence that
      exposure to plutonium aerosols significantly affects the risk associated with
      external exposure. While the Mayak external dose risk estimate of an excess
      relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized
      risk estimate from the Life Span Study of Japanese atomic bomb survivors, the
      uncertainties in these estimates preclude concluding that the external dose
      excess relative risks of this group of solid cancers differ in the two cohorts.

PMID- 27695961
TI  - Targeted proteomics for the indirect detection of dexamethasone treatment in
      bovines.
AB  - The illegal use of pharmacologically active compounds for growth promotion in
      food-producing species poses risks for consumer health and animal welfare.
      Surveillance relies on the quantification of drug residues in animal fluids or
      tissues, but the efficacy can be negatively affected due to undetectable residual
      concentrations in biological matrices. Consequently, techniques focusing on the
      indirect biological effects of exogenous compound administration have been
      proposed as more sensitive detection methods. The purpose of the present study is
      to develop a tandem mass spectrometry analytical method based on low-energy
      collision-induced dissociation (CID-MS/MS) using multiple reaction monitoring
      (MRM) for the quantification of 12 potential protein markers of skeletal muscle
      to detect anabolic treatments with dexamethasone. Protein markers identified in a
      previous study applying a 2D-DIGE proteomics approach have been quantified using
      the signature peptide method. A group of proteins were confirmed as reliable
      markers. Quantitative results enabled a predictive model to be defined based on
      logistic regression for the detection of treated animals. The developed model was
      finally cross-validated in an independent animal set. Graphical abstract
      Analytical workflow used for the quantification of indirect protein markers of
      dexamethasone treatment.

PMID- 27695963
TI  - Quantification of antibody coupled to magnetic particles by targeted mass
      spectrometry.
AB  - Quantifying the amount of antibody on magnetic particles is a fundamental, but
      often overlooked step in the development of magnetic separation-based
      immunoaffinity enrichment procedures. In this work, a targeted mass spectrometry
      (MS)-based method was developed to directly measure the amount of antibody
      covalently bound to magnetic particles. Isotope-dilution liquid chromatography
      tandem MS (ID-LC-MS/MS) has been extensively employed as a gold-standard method
      for protein quantification. Here, we demonstrate the utility of this methodology
      for evaluating different antibody coupling processes to magnetic particles of
      different dimensions. Synthesized magnetic nanoparticles and pre-functionalized
      microparticles activated with glutaraldehyde or epoxy surface groups were used as
      solid supports for antibody conjugation. The key steps in this quantitative
      approach involved an antibody-magnetic particle coupling process, a wash step to
      remove unreacted antibody, followed by an enzymatic digestion step (in situ with
      the magnetic particles) to release tryptic antibody peptides. Our results
      demonstrate that nanoparticles more efficiently bind antibody when compared to
      microparticles, which was expected due to the larger surface area per unit mass
      of the nanoparticles compared to the same mass of microparticles. This
      quantitative method is shown to be capable of accurately and directly measuring
      antibody bound to magnetic particles and is independent of the conjugation method
      or type of magnetic particle. Graphical Abstract Schematic illustration of the
      isotope-dilution mass spectrometry-based workflow to directly measure antibody
      bound to magnetic particles (MP).

PMID- 27695962
TI  - Isotope-targeted glycoproteomics (IsoTaG) analysis of sialylated N- and O
      glycopeptides on an Orbitrap Fusion Tribrid using azido and alkynyl sugars.
AB  - Protein glycosylation is a post-translational modification (PTM) responsible for
      many aspects of proteomic diversity and biological regulation. Assignment of
      intact glycan structures to specific protein attachment sites is a critical step
      towards elucidating the function encoded in the glycome. Previously, we developed
      isotope-targeted glycoproteomics (IsoTaG) as a mass-independent mass spectrometry
      method to characterize azide-labeled intact glycopeptides from complex proteomes.
      Here, we extend the IsoTaG approach with the use of alkynyl sugars as metabolic
      labels and employ new probes in analysis of the sialylated glycoproteome from PC
      3 cells. Using an Orbitrap Fusion Tribrid mass spectrometer, we identified 699
      intact glycopeptides from 192 glycoproteins. These intact glycopeptides represent
      a total of eight sialylated glycan structures across 126 N- and 576 O
      glycopeptides. IsoTaG is therefore an effective platform for identification of
      intact glycopeptides labeled by alkynyl or azido sugars and will facilitate
      further studies of the glycoproteome.

PMID- 27695965
TI  - Soy Protein: Its Effects on Intestinal Calcium Transport, Serum Vitamin D, and
      Insulin-like Growth Factor-I in Ovariectomized Rats.

PMID- 27695964
TI  - Killer immunoglobulin-like receptor (KIR) and KIR-ligand genotype do not
      correlate with clinical outcome of renal cell carcinoma patients receiving high
      dose IL2.
AB  - NK cells play a role in many cancer immunotherapies. NK cell activity is tightly
      regulated by killer immunoglobulin-like receptor (KIR) and KIR-ligand
      interactions. Inhibitory KIR-ligands have been identified as HLA molecules, while
      activating KIR-ligands are largely unknown. Individuals that have not inherited
      the corresponding KIR-ligand for at least one inhibitory KIR gene are termed the
      "KIR-ligand missing" genotype, and they are thought to have a subset of NK cells
      that express inhibitory KIRs for which the corresponding KIR-ligand is missing on
      autologous tissue, and thus will not be inhibited through KIR-ligand recognition.
      In some settings where an anticancer immunotherapeutic effect is likely mediated
      by NK cells, individuals with a KIR-ligand missing genotype have shown improved
      clinical outcome compared to individuals with an "all KIR-ligands present"
      genotype. In addition, patients receiving hematopoietic stem cell transplants for
      leukemia may do better if their donor has more activating KIR genes (i.e., KIR
      haplotype-B). In a recent multi-institution clinical trial of patients with
      metastatic renal cell carcinoma receiving high-dose IL2 (HD-IL2), 25 % of
      patients showed a complete or partial tumor response to this therapy. We
      genotyped KIR and KIR-ligand genes for these patients (n = 107) and tested
      whether KIR/KIR-ligand genotypes correlated with patient clinical outcomes. In
      these analyses, we did not find any significant association of KIR/KIR-ligand
      genotype (either KIR-ligand missing or the presence of KIR haplotype-B) with
      patient outcome in response to the HD-IL2 therapy.

PMID- 27695968
TI  - Unusual meandering right upper lobe pulmonary vein draining into right middle
      lobe pulmonary vein: a case report.
AB  - Meandering right pulmonary vein is a rare vascular anomaly that requires accurate
      diagnosis to avoid unnecessary procedures and unintended vascular injury during
      operation. We describe an unusual meandering right upper lobe pulmonary vein
      draining into the left atrium via the right middle lobe pulmonary vein.

PMID- 27695967
TI  - Surfactant-induced bacterial community changes correlated with increased
      polycyclic aromatic hydrocarbon degradation in contaminated soil.
AB  - Bioremediation as a method for removing polycyclic aromatic hydrocarbons (PAHs)
      from contaminated environments has been criticized for poor removal of
      potentially carcinogenic but less bioavailable high molecular weight (HMW)
      compounds. As a partial remedy to this constraint, we studied surfactant addition
      at sub-micellar concentrations to contaminated soil to enhance the biodegradation
      of PAHs remaining after conventional aerobic bioremediation. We demonstrated
      increased removal of four- and five-ring PAHs using two nonionic surfactants,
      polyoxyethylene(4)lauryl ether (Brij 30) and polyoxyethylene sorbitol hexaoleate
      (POESH), and analyzed bacterial community shifts associated with those
      conditions. Eight groups of abundant bacteria were implicated as potentially
      being involved in increased HMW PAH removal. A group of unclassified
      Alphaproteobacteria and members of the Phenylobacterium genus in particular
      showed significantly increased relative abundance in the two conditions
      exhibiting increased PAH removal. Other implicated groups included members of the
      Sediminibacterium, Terrimonas, Acidovorax, and Luteimonas genera, as well as
      uncharacterized organisms within the families Chitinophagaceae and
      Bradyrhizobiaceae. Targeted isolation identified a subset of the community likely
      using the surfactants as a growth substrate, but few of the isolates exhibited
      PAH-degradation capability. Isolates recovered from the Acidovorax and
      uncharacterized Bradyrhizobiaceae groups suggest the abundance of those groups
      may have been attributable to growth on surfactants. Understanding the specific
      bacteria responsible for HMW PAH removal in natural and engineered systems and
      their response to stimuli such as surfactant amendment may improve bioremediation
      efficacy during treatment of contaminated environmental media.

PMID- 27695970
TI  - The cut surface of the neck as depicted in two paintings of Judith and
      Holofernes.

PMID- 27695969
TI  - Fenestration of the supraclinoid internal carotid artery arising from the
      paraclinoid aneurysmal dilatation and fusing with the origin of the posterior
      communicating artery: a case report.
AB  - We report an extremely rare case of fenestration of the supraclinoid internal
      carotid artery (ICA) diagnosed by magnetic resonance (MR) angiography. The
      smaller channel arose from the paraclinoid ICA aneurysmal dilatation, and the
      posterior communicating artery arose from the distal end of the fenestration.
      Careful observation of MR angiographic images, including source images, is
      important to detect rare arterial variations, and their identification on MR
      angiography is aided by the creation of partial maximum-intensity-projection
      images and partial volume-rendering images.

PMID- 27695971
TI  - Patient-specific factors influencing the traction forces in hip arthroscopy.
AB  - INTRODUCTION: The application of traction in hip arthroscopy is associated with
      peri-operative complications. Within a therapeutic case series, patient-related
      factors correlating with high-traction forces during hip arthroscopy and
      occurring complications should be identified. MATERIALS AND METHODS: In 30 male
      and 38 female patients (mean age: 44.5 years), intra-operative traction forces
      were monitored continuously using a specialised measurement device. A
      multivariate analysis was employed to identify patient-related factors
      influencing the traction force. Peri-operative complications (follow-up: 12
      weeks) were evaluated by performing a single-case analysis. RESULTS: The mean
      initial force prior to penetration of the capsule ("initial force") was 477 N
      (men: 517 N; women: 444 N), decreasing after capsulotomy by an average of 17 %.
      The male gender (p < 0.001), Kellgren and Lawrence radiographic stage (p =
      0.037), low minimum joint-space width (p = 0.029) and high body height/weight (p
      = 0.003/0.037) correlated significantly with higher distraction forces. The
      patient age and type of anaesthesia (general versus spinal) were not relevant.
      Complications were observed in ten patients on the first post-operative day. In
      two of these patients a partial sensory deficit of the lateral cutaneous femoral
      nerve persisted after 12 weeks. All patients with complications required initial
      traction forces of >400 N. CONCLUSIONS: The study revealed several patient
      specific risk factors correlating with high-traction forces during hip
      arthroscopy. With view to potential complications, these patient groups require
      special attention during surgical treatment as well as in future studies.

PMID- 27695972
TI  - Aliskiren decreases oxidative stress and angiogenic markers in retinal pigment
      epithelium cells.
AB  - There is growing evidence on the role of ocular renin-angiotensin system (RAS) in
      the development of diabetic retinopathy (DR), particularly due to the trigger of
      oxidative stress and angiogenesis. Despite this there is no effective RAS-based
      therapy in DR capable of preventing retinal damage induced by RAS activation. We
      recently described that retinal pigment epithelium (RPE) cells express the main
      components of the RAS. We here propose to investigate the role of glucose upon
      the retinal RAS and whether aliskiren, a direct renin inhibitor, protects RPE
      cells from angiogenesis and oxidative stress. RPE cells were chosen as target
      since one of the first events in DR is the dysfunction of the RPE retinal layer,
      which as a key function in maintaining the integrity of the retina. We found that
      the RAS present in the RPE cells was deregulated by hyperglycemic glucose
      concentrations. Exposure of RPE cells to angiotensin II increased the levels of
      the main pro-angiogenic factor, vascular endothelial growth factor (VEGF) in a
      concentration-dependent manner. Additionally, angiotensin II also stimulated the
      production of reactive oxygen species in RPE cells. Treatment of RPE cells with
      aliskiren decreased the levels of oxidative stress and promoted the expression of
      anti-angiogenic factors such as the pigment epithelium-derived factor and the
      VEGF165b isoform. Our findings demonstrate that the RAS is deregulated in
      hyperglycemic conditions and that aliskiren successfully protected RPE cells from
      RAS over activation. These anti-angiogenic and antioxidant properties described
      for aliskiren over RPE cells suggest that this drug has potential to be used in
      the treatment of diabetic retinopathy.

PMID- 27695973
TI  - Is gastroscopy for fecal immunochemical test positive patients worthwhile?
AB  - BACKGROUND: The use of fecal immunochemical test (FIT) in the screening for
      colorectal cancer is long established. However, more than 50 % of patients with
      positive FITs have a negative colonoscopy. The role of a subsequent oesophago
      gastro-duodenoscopy (OGD) is debatable. The aim of this study is to evaluate the
      yield of OGD in patients with positive FITs. METHODOLOGY: A retrospective review
      of patients who underwent colonoscopy for a positive FIT between Jan. 2008 and
      Dec. 2012 was identified from a prospectively collected endoscopy database at the
      National University Hospital, Singapore. Patients who underwent concurrent or
      subsequent OGDs for positive FIT formed the study group. We considered any new
      cancer or significant upper gastrointestinal pathology such as peptic ulcer
      disease or gastritis requiring treatment as a positive examination. RESULTS: A
      total of 202 patients underwent both a colonoscopy and an OGD for a positive FIT
      and formed the study group. One hundred and six (52.5 %) of them had a positive
      examination with gastritis and duodenitis representing the most common UGI
      pathology in 89 (44.1 %) patients. Twenty-nine (14.4 %) patients tested positive
      for helicobacter pylori infection and another 16 (7.9 %) patients had peptic
      ulcer disease. There were no UGI cancers detected. One patient had an esophageal
      leiomyoma that was treated conservatively. CONCLUSION: Routine gastroscopy for
      FIT positivity has a high diagnostic yield for benign upper gastrointestinal
      pathology. Well-designed prospective studies to further evaluate the cost
      effectiveness of routine gastroscopy in the work up of FIT positivity are
      warranted to make better clinical practice guidelines.

PMID- 27695974
TI  - Gastrointestinal tract anastomoses with the biofragmentable anastomosis ring: is
      it still a valid technique for bowel anastomosis? Analysis of 203 cases and
      review of the literature.
AB  - PURPOSE: Biofragmentable anastomosis ring (BAR) is an alternative to manual and
      stapled anastomoses performed within the upper and lower gastrointestinal (GI)
      tract. The aim of this study was to evaluate the effectiveness of BAR utility for
      bowel anastomoses based on our own material. METHODS: A retrospective analysis
      was performed to a total of 203 patients who underwent bowel surgery with the use
      of BAR anastomosis within upper and lower gastrointestinal tract between 2004 and
      2014. Data for the analysis was collected based on medical records, treatment
      protocols, and the results of histological examinations. RESULTS: The study group
      consisted of 86 women and 117 men. The most common underlying pathology was a
      malignant disease (n = 165). Biofragmentable anastomosis ring (BAR) size 31 was
      the most commonly used (n = 87). A total of 169 colocolic or colorectal
      anastomoses and 28 ileocolic and 8 enteroenteric anastomoses were performed. The
      mortality rate was 0.5 % (n = 1) whereas re-surgery rate within 30 days was 8.4 %
      (n = 17). Twenty-eight patients developed perioperative complications with
      surgical site infection as the most common one (n = 11). Eight patients developed
      specific complications associated with BAR including an anastomotic leak (n = 6)
      and intestinal obstruction (n = 2). The mean time of hospital stay after surgery
      was 12.7 days. CONCLUSIONS: The use of BAR for the GI tract anastomoses is simple
      and rapid method and it is characterized with an acceptable number of
      perioperative mortality and complication rates. Based on our experience, we
      recommend the use of BAR anastomosis in different types of intestinal anastomosis
      in varying clinical scenarios.

PMID- 27695975
TI  - Long-term response to gluten-free diet as evidence for non-celiac wheat
      sensitivity in one third of patients with diarrhea-dominant and mixed-type
      irritable bowel syndrome.
AB  - PURPOSE: Irritable bowel syndrome (IBS) is common but therapies are
      unsatisfactory. Food is often suspected as cause by patients, but diagnostic
      procedures, apart from allergy testing, are limited. Based on the hypothesis of
      non-celiac wheat sensitivity (WS) in a subgroup of IBS patients, we tested the
      long-term response to a gluten-free diet (GFD) and investigated HLA-DQ2 or -DQ8
      expression as a diagnostic marker for WS in diarrhea-dominant (IBS-D) and mixed
      type IBS (IBS-M). METHODS: The response to a GFD served as reference test for WS
      and HLA-DQ2/8 expression was determined as index test. Patients were classified
      as responders if they reported complete or considerable relief of IBS symptoms on
      at least 75 % of weeks over a 4-month period of gluten-free diet. Established
      questionnaires (IBS-Quality of Life (IBS-QoL), IBS Symptom Severity Scale (IBS
      SSS), European Quality of Life-5 Dimensions (EQ-5D)) were used for secondary
      outcome measures. RESULTS: Thirty-five patients finished the study. Of these, 12
      (34 %) were responders and classified as having WS (95 % CI 21-51 %). HLA-DQ2/8
      expression had a specificity of 52 % (95 % CI 33-71 %) and sensitivity of 25 %
      (95 % CI 8-54 %) for WS. Responders showed improvement in quality of life and
      symptom scores. At 1-year follow-up, all responders and 55 % of non-responders
      were still on GFD and reported symptom relief. CONCLUSION: Using strict criteria
      as recommended for IBS studies, about one third of patients with IBS-D or IBS-M
      are wheat sensitive, with a similar proportion in both IBS types. Expression of
      HLA-DQ2/8 is not useful as diagnostic marker for WS. Long-term adherence to a GFD
      is high and can sustain symptomatic improvement.

PMID- 27695976
TI  - Long-term functional follow-up after anterior rectal resection for cancer.
AB  - PURPOSE: This is a retrospective analysis including all of the patients that have
      undergone anterior resection for rectal cancer from January 1998 to December 2005
      in two tertiary referral centers. The study aims to evaluate the long term
      functional results after low anterior resection and to identify the risk factors
      of postoperative bowel disorders. METHOD: Data were collected from the clinical
      records, and then the low anterior resection syndrome score which is a specific
      questionnaire to investigate the symptoms after surgery was submitted to the
      selected patients. Exclusion criteria were intra-abdominal rectal cancer, partial
      mesorectal excision, permanent stoma, recurrent local disease, and patients who
      declined the questionnaire. RESULTS: A total of 93 patients were included in the
      analysis with a median age at the diagnosis of 66 years. The median follow-up was
      13.7 years, and low anterior resection syndrome was reported in 44 patients (47.5
      %), with major manifestations in 19 patients (20.5 %), and minor symptoms in 25
      patients (27 %). Age more than 70 years, tumor distance from the external anal
      verge, neoadjuvant treatment, and interval time of closing stoma are independent
      prognostic factors of functional disorders after surgery. CONCLUSIONS: Because of
      its great impact on the quality of life of these patients, it is necessary to
      early identify the syndrome trying to reduce its manifestations. Moreover, the
      symptoms seem to remain stable 1 year after surgery; hence, it is important to
      have an exhaustive, preoperative counseling and an integrated post-operative
      functional and rehabilitational follow-up in association with the oncologic
      pathway.

PMID- 27695977
TI  - Evaluation of lymph flow patterns in splenic flexural colon cancers using
      laparoscopic real-time indocyanine green fluorescence imaging.
AB  - PURPOSE: The treatment of splenic flexural colon cancer is not standardized
      because the lymphatic drainage is variable. The aim of this study is to evaluate
      the lymph flow at the splenic flexure. METHODS: From July 2013 to January 2016,
      consecutive patients of the splenic flexural colon cancer with a preoperative
      diagnosis of N0 who underwent laparoscopic surgery were enrolled. Primary outcome
      is frequency of the direction of lymph flow from splenic flexure. We injected
      indocyanine green (2.5 mg) into the submucosal layer around the tumor and
      observed lymph flow using the laparoscopic near-infrared camera system in 30 min
      after injection. RESULTS: Thirty-one patients were enrolled in this study. The
      lymph flow was visualized in 31 patients (100 %) without any complications. No
      case exhibited lymph flow in both the left colic artery (LCA) and left branch of
      the middle colic artery (lt-MCA) areas. There were 19 cases (61.3 %) with lymph
      flow directed to the area of the root of the inferior mesenteric vein (IMV),
      regardless of the presence of the left accessory aberrant colic artery. Lymph
      node metastases were observed in six cases (19.4 %), and all of the involved
      lymph nodes existed in lymph flow areas determined by real-time indocyanine green
      fluorescence imaging. CONCLUSIONS: The findings of the lymph flow pattern of
      splenic flexure suggest that lymph node dissection at the root of the IMV area is
      important, and it may be not necessary to ligate both the lt-MCA and LCA, at
      least in cases without widespread lymph node metastases.

PMID- 27695979
TI  - Aging and the effects of a half marathon on Achilles tendon force-elongation
      relationship.
AB  - PURPOSE: We aimed to determine whether there are different changes in Achilles
      tendon (AT) mechanical properties in middle-aged, compared to younger runners
      that might indicate that tendon fatigue, induced by long-distance running, is age
      dependent. METHODS: 27 middle-aged (50-67 years) and 22 younger (21-29 years)
      participants ran a 21 km route at their own pace (mean and SD: old: 3.1 +/- 0.3 m
      s-1; young: 3.6 +/- 0.5 m s-1). We tested for changes in the AT force-elongation
      relationship using dynamometry and ultrasonography during isometric voluntary
      ankle plantarflexion ramp contractions, conducted 20-28 h pre-run, immediately
      pre-run, immediately post-run and 20-28 h post-run. Stride frequency and number
      were examined to estimate cyclic tensile loading characteristics of the tendon
      during running. RESULTS: Muscle strength decreased significantly (P < 0.05) in
      both groups immediately post-run (old: 17 %; young: 11 %) and recovered to
      baseline within 20-28 h post-run. AT stiffness did not change for the younger
      adults, whereas the middle-aged adults showed a significant (P < 0.05) decrease
      in AT stiffness (22 %). However, tendon stiffness recovered to baseline 20-28 h
      post-run. Middle-aged, compared to young adults, demonstrated significantly (P <
      0.05) greater stride frequency and number, but no correlations with tendon
      fatigue changes were determined (R 2 <= 0.038). CONCLUSIONS: The results suggest
      that the plasticity of the AT in response to short-term mechanical loading may be
      age dependent and that the AT length-tension properties of middle-aged runners
      may be more vulnerable to change following running compared to younger athletes.
      However, the observed AT changes in the middle-aged runners dissipated within 20
      28 h post-run, suggesting that a tendon viscoelastic recovery mechanism may occur
      in vivo.

PMID- 27695978
TI  - Differential vascular reactivity responses acutely following ingestion of a
      nitrate rich red spinach extract.
AB  - INTRODUCTION: Inorganic nitrate ingestion has been posited to affect arterial
      blood pressure and vascular function. PURPOSE: We sought to determine the acute
      effect of a red spinach extract (RSE) high in inorganic nitrate on vascular
      reactivity 1-h after ingestion in peripheral conduit and resistance arteries.
      METHODS: Fifteen (n = 15; males 8, females 7) apparently healthy subjects (aged
      23.1 +/- 3.3 years; BMI 27.2 +/- 3.7 kg/m2) participated in this crossover
      design, double-blinded study. Subjects reported to the lab >=2-h post-prandial
      and consumed RSE (1000 mg dose; ~90 mg nitrate) or placebo (PBO). Venipuncture
      was performed on three occasions: baseline, 30-min post-ingestion and between 65
      to 75-min post-ingestion. Baseline vascular measurements [i.e., calf venous
      occlusion plethysmography, brachial artery flow-mediated dilation (FMD)], 30-min
      of continuous blood pressure (BP) and heart rate (HR) analysis, and follow-up
      vascular measurements beginning at 40-min post-ingestion were also performed.
      RESULTS: Humoral nitrate following RSE ingestion was significantly higher at 30-
      (+54 %; P = 0.039) and 65 to 75-min post-ingestion compared to baseline (+255 %,
      P < 0.001) and PBO at the same time points (P < 0.05). No significant changes in
      BP or HR occurred in either condition. Peak reactive hyperemia (RH) calf blood
      flow increased significantly (+13.7 %; P = 0.016) following RSE ingestion,
      whereas it decreased (-14.0 %; P = 0.008) following PBO ingestion. No significant
      differential FMD responses were detected (P > 0.05), though RH was decreased
      following the baseline measure in both conditions. CONCLUSIONS: RSE significantly
      increased plasma nitrate 30-min post-ingestion, but acute microvascular (i.e.,
      resistance vasculature) reactivity increases were isolated to the lower limb and
      no appreciable change in brachial artery FMD was observed.

PMID- 27695980
TI  - Effects of caffeine ingestion on endurance performance in mentally fatigued
      individuals.
AB  - PURPOSE: To examine the effects of caffeine ingestion on physiological and
      perceptual responses in mentally fatigued individuals. METHODS: Eight male
      physically active subjects completed four cycling constant-workload tests in four
      experimental conditions at 80 % of maximal power output: control (C), mental
      fatigue (MF), mental fatigue plus caffeine ingestion (5 mg/kg) (MF-CAF), and
      mental fatigue plus placebo (MF-PLA). The mental fatigue was induced by a
      continuous performance task A-X version (AX-CPT). Before and after the AX-CPT,
      the profile of mood state (POMS) and blood samples for lactate measurement were
      collected. Oxygen consumption ([Formula: see text]), rating of perceived exertion
      (RPE), and electromyography (EMG) activity were measured during the cycling test.
      RESULTS: The time to exhaustion in C, MF, MF-PLA, and MF-CAF were 251 +/- 30, 222
      +/- 23, 248 +/- 28, and 285 +/- 42 s, respectively. Delta values (corrected by C
      condition) were higher in MF-CAF than MF (P = 0.031). MF-CAF reported higher
      Vigor scores when compared with C (P = 0.046) and MF (P = 0.020). RPE at the
      first minute was significantly higher in MF-PLA than in C (P = 0.050); at the
      second minute, RPE was higher in MF-PLA than in C (P = 0.049) and MF-CAF (P =
      0.048). EMG activity was not different between the conditions. CONCLUSIONS:
      Caffeine ingestion increased approximately 14 % endurance performance after the
      induction of mental fatigue. This effect was accompanied by a tendency to
      improvement in mood state (i.e., vigor). Therefore, caffeine ingestion can
      promote a beneficial effect on endurance performance in mentally fatigued
      individuals.

PMID- 27695981
TI  - Arthroscopic treatment of symptomatic discoid meniscus in children.
AB  - PURPOSE: To study discoid meniscus in children who underwent arthroscopic surgery
      at our center. SUBJECTS AND METHODS: Thirty-four patients (39 knees) younger than
      15 years with discoid lateral meniscus (mean age, 12.9 years; 13 males, 21
      females) who underwent arthroscopic surgeries since 2007 were studied. The
      surgical procedure consisted of, in principle, saucerization with additional
      suture repair in the case of meniscal instability at the peripheral rim of the
      residual meniscus. The mechanisms of symptom onset, symptoms, complications and
      postoperative outcome in these cases were examined. In addition, Lysholm scores
      were obtained before surgery and at the last postoperative follow-up in all
      patients. RESULTS: Symptom onset was associated with sports in 18 knees, fall in
      3 knees, and no definitive trigger in the remaining knees. The presenting
      symptoms were pain in 32 knees, catching in 11 knees, and locking in 6 knees.
      According to Watanabe classification, 26 knees were complete type and 13 knees
      were incomplete type. The modes of tear included horizontal tear in 10 knees and
      longitudinal tear in 10 knees, while no definitive tear was present on the knee
      joint surface. The surgical procedures included saucerization only in 22 knees,
      partial meniscectomy in 10 knees, and saucerization with suture repair in 5
      knees. The mean Lysholm score was 63.9 before surgery, and improved significantly
      to 92.3 at the last follow-up. Only two knees developed osteochondritis dissecans
      after surgery. Two knees required reoperation; one knee underwent subtotal
      meniscectomy and one knee had partial meniscectomy with suturing. CONCLUSION:
      Although the short-term outcome after saucerization with or without suture repair
      for discoid meniscus is favorable, degenerative change or change of lower limb
      alignment may occur in the long term. Further long-term study is required.

PMID- 27695982
TI  - Harbin: a quantitation PCR analysis tool.
AB  - OBJECTIVES: To enable analysis and comparisons of different relative quantitation
      experiments, a web-browser application called Harbin was created that uses a
      quantile-based scoring system for the comparison of samples at different time
      points and between experiments. RESULTS: Harbin uses the standard curve method
      for relative quantitation to calculate concentration ratios (CRs). To evaluate if
      different datasets can be combined the Harbin quantile bootstrap test is
      proposed. This test is more sensitive in detecting distributional differences
      between data sets than the Kolmogorov-Smirnov test. The utility of the test is
      demonstrated in a comparison of three grapevine leafroll associated virus 3
      (GLRaV-3) RT-qPCR data sets. CONCLUSIONS: The quantile-based scoring system of
      CRs will enable the monitoring of virus titre or gene expression over different
      time points and be useful in other genomic applications where the combining of
      data sets are required.

PMID- 27695983
TI  - Development and validation of the modular Feed-code method for qualitative and
      quantitative determination of feed botanical composition.
AB  - The analysis of feed composition in terms of ingredients is addressed by
      Regulation (EC) 767/2009 and is important for detecting economic fraud and for
      monitoring feed safety. Within the framework of the EU project Feed-code, we
      developed and internally validated a modular assay, relying on intron
      polymorphism, for the complete qualitative analysis of the botanical composition
      of feed and the quantitative determination of six target plant species. Main
      performance parameters of each module, such as applicability, repeatability,
      specificity, and limit of detection, were evaluated. The whole assay was applied
      to a set of feed-like samples and results were in agreement with the expected
      composition. Application to a large set of compound feed and individual raw
      materials revealed the occurrence of botanical impurities. When compared with
      microscopic analysis, the proposed method gave more reliable results. We conclude
      that the Feed-code prototype, readily upgradable to include more plant species,
      is worthy of consideration for a full validation through a collaborative trial.
      Graphical Abstract The modular Feed-code method for the authentication of feed
      botanical composition.

PMID- 27695984
TI  - Introduction to polymer-based solid-contact ion-selective electrodes-basic
      concepts, practical considerations, and current research topics.
AB  - This review aims at providing an introductory overview for researchers new to the
      field of ion-selective electrodes. Both state of the art technology and novel
      developments towards solid-contact reference (sc-RE) and solid-contact ion
      selective electrodes (sc-ISE) are discussed. This technology has potentially
      widespread and important applications provided certain performance criteria can
      be met. We present basic concepts, operation principles, and theoretical
      considerations with regard to their function. Analytical performance and
      suitability of sc-RE and sc-ISE for a given application depend on critical
      parameters, which are discussed in this review. Comprehensive evaluation of
      sensor performance along this set of parameters is considered indispensable to
      allow for a well-founded comparison of different technologies. Methods and
      materials employed in the construction of sc-RE and sc-ISE, in particular the
      solid contact and the polymer membrane composite, are presented and discussed in
      detail. Operation principles beyond potentiometry are mentioned, which would
      further extend the field of ISE application. Finally, we conclude by directing
      the reader to important areas for further scientific research and development
      work considered particularly critical and promising for advancing this field in
      sensor R&D. Graphical Abstract ?.

PMID- 27695985
TI  - Limitations of turbidity process probes and formazine as their calibration
      standard.
AB  - Turbidity measurements are frequently implemented for the monitoring of
      heterogeneous chemical, physical, or biotechnological processes. However, for
      quantitative measurements, turbidity probes need calibration, as is requested and
      regulated by the ISO 7027:1999. Accordingly, a formazine suspension has to be
      produced. Despite this regulatory demand, no scientific publication on the
      stability and reproducibility of this polymerization process is available. In
      addition, no characterization of the optical properties of this calibration
      material with other optical methods had been achieved so far. Thus, in this
      contribution, process conditions such as temperature and concentration have been
      systematically investigated by turbidity probe measurements and Photon Density
      Wave (PDW) spectroscopy, revealing an influence on the temporal formazine
      formation onset. In contrast, different reaction temperatures do not lead to
      different scattering properties for the final formazine suspensions, but give an
      access to the activation energy for this condensation reaction. Based on PDW
      spectroscopy data, the synthesis of formazine is reproducible. However, very
      strong influences of the ambient conditions on the measurements of the turbidity
      probe have been observed, limiting its applicability. The restrictions of the
      turbidity probe with respect to scatterer concentration are examined on the basis
      of formazine and polystyrene suspensions. Compared to PDW spectroscopy data,
      signal saturation is observed at already low reduced scattering coefficients.

PMID- 27695986
TI  - Structural modifications of cellulose samples after dissolution into various
      solvent systems.
AB  - This work deals with the modifications resulting from the dissolution of four
      commercial cellulosic samples, with different crystallinity rates and degrees of
      polymerization (DPs), in four solvent systems, known and used to dissolve
      cellulose. The dissolution conditions were optimized for the 16 various systems
      and followed by turbidity measurements. After regeneration, the samples were
      analyzed by thermal gravimetric analysis (TGA), scanning electron microscopy
      (SEM), and X-ray diffractometry (XRD) to study their modification. Viscosimetry
      measurements were used to evaluate the potential decrease of the DP after
      dissolution. The observed structural modifications established that, for low DP,
      all the solvent systems were efficient in dissolving the cellulose without
      altering the DP, except BMIM [Cl], which provoked a decrease of up to 40 % and a
      decrease of around 20 % of the degradation temperature (onset temperature, T o).
      For high molecular weight (MW) celluloses, DMSO/TBAF was the only system to allow
      a complete dissolution without any molar mass loss and degradation temperature
      modification.

PMID- 27695987
TI  - Variation in estimated glomerular filtration rate at dialysis initiation in
      children.
AB  - BACKGROUND: Data guiding the timing of dialysis initiation in children are
      limited. We sought to determine current practice and secular trends in Canada
      with respect to the timing of dialysis initiation in children based on estimated
      glomerular filtration rate (eGFR). METHODS: This observational study included
      incident chronic dialysis patients aged <=21 years identified from the Canadian
      Organ Replacement Register who started dialysis in Canada between January 2001
      and December 2010 at any of the nine participating Canadian centers (n = 583).
      Youth were categorized utilizing CKiD Schwartz eGFR into >=10.5 (higher) or <10.5
      ml/min/1.73 m2 (lower) eGFR groups. Differences at dialysis initiation by
      facility and region were examined, and secular trends were determined. RESULTS:
      Median eGFR at dialysis initiation was 8.1 (interquartile range 5.4-11.0)
      ml/min/1.73 m2. Overall, 29 % of the patients started dialysis with an eGFR of
      >=10.5 ml/min/1.73 m2. The proportion of children starting with higher eGFR
      increased from 27.3 % in 2001 to 35.4 % in 2010 (p = 0.04) and differed by
      treatment facility (12-70 %; p = 0.0001). Factors associated with higher eGFR at
      dialysis initiation in the adjusted regression model were female sex [odds ratio
      (OR) 1.48; 95 % confidence interval (CI) 1.02-2.14], genetic cause of end-stage
      kidney disease (OR 2.77; 95 % CI 1.37-5.58) and living >=50 km from treatment
      facility (OR 1.47; 95 % CI 1.01-2.14). CONCLUSIONS: One-third of the children
      were found to have initiated dialysis with an eGFR >=10.5 ml/min/1.73 m2, however
      significant practice variation exists with respect to timing of dialysis
      initiation by treatment facility. More data is required to evaluate the clinical
      implications of this practice variation.

PMID- 27695988
TI  - Prognosis in patients with atrial fibrillation and a presumed "temporary cause"
      in a community-based cohort study.
AB  - BACKGROUND: Atrial fibrillation (AF) may be related to acute and temporary
      causes, whether cardiovascular or non-cardiovascular. It remains unclear whether
      the risk of ischemic stroke is different in this setting, and whether
      antithrombotic management should be different in these patients. The objective of
      the study was to describe and compare the risk of stroke in AF patients with and
      with no such temporary precipitating cause. METHODS: Among 8962 patients with AF
      seen between 2000 and 2010, we focused our analysis on 4587 patients with non
      permanent AF, of whom 740 (16 %) had at least one possible temporary cause of AF.
      RESULTS: During a mean follow-up of 944 days (median 451, interquartile range 8
      1624), the adjusted rates of stroke/TE were non-significantly different between
      patients with a temporary cause of AF and other AF patients (HR = 1.08, 95 % CI
      0.82-1.41, p = 0.59 after adjustment on age, gender, CHA2DS2VASc score, OAC use
      and antiplatelet therapy use). Cardiovascular mortality was higher in patients
      with a temporary cause when compared to other AF patients (adjusted HR = 1.42, 95
      % CI 1.08-1.86, p = 0.01). In patients with a temporary cause of AF, prescription
      of oral anticoagulation was independently associated with a better prognosis for
      cardiovascular death/stroke/thromboembolism (HR = 0.44, 95 % CI 0.29-0.67, p =
      0.0001). CONCLUSION: AF patients with presumed temporary cause of AF had a
      similar risk of stroke/thromboembolism and a worse prognosis for cardiovascular
      mortality than other AF patients. Use of oral anticoagulation was associated with
      a better prognosis in these patients.

PMID- 27695989
TI  - Low level exercise echocardiography helps diagnose early stage heart failure with
      preserved ejection fraction: a study of echocardiography versus catheterization.
AB  - BACKGROUND: Increased left ventricular end-diastolic pressure (LVEDP) with
      exercise is an early sign of heart failure with preserved left ventricular
      ejection fraction (LVEF). The abnormal exercise increase in LVEDP is nonlinear,
      with most change occurring at low-level exercise. Data on non-invasive approach
      of this condition are scarce. Our objective was assessing E/e' to estimate low
      level exercise LVEDP using a direct invasive measurement as the reference method.
      METHODS AND RESULTS: Sixty patients with LVEF >50 % prospectively underwent both
      exercise cardiac catheterization and echocardiography. E/e' was measured at rest
      and during low-level exercise. Abnormal LVEDP was defined as >16 mmHg. Patients
      with a history of coronary artery disease and/or abnormal LV morphology were
      classified as having apparent cardiac disease (CD). Thirty-four (57 %) patients
      had elevated LVEDP only during exercise. Most of the change in LVEDP occurred
      since the first exercise level (25 W). There was a correlation between LVEDP and
      septal E/e' at rest and during exercise. Lateral E/e' and E/average e' ratio had
      worse correlations with LVEDP. In the whole population, exercise septal E/e' at
      25 W had the best accuracy for abnormal exercise LVEDP, area under curve (AUC) =
      0.79. However, while low-level exercise septal E/e' had a high accuracy in CD
      patients (n = 26, AUC = 0.96), E/e' was not linked to LVEDP in patients without
      CD (n = 34). CONCLUSION: Low-level exercise septal E/e' is valuable for
      predicting abnormal exercise LVEDP in patients with preserved LVEF and apparent
      CD. However, this new diagnosis approach appears not reliable in patients with
      normal LV morphology and without coronary artery disease. CLINICAL TRIAL
      REGISTRATION: https://clinicaltrials.gov . Unique identifier: NCT01714752.

PMID- 27695990
TI  - Functional and genetic predisposition to rhinovirus lower respiratory tract
      infections in prematurely born infants.
AB  - : Term born infants are predisposed to human rhinovirus (HRV) lower respiratory
      tract infections (LRTI) by reduced neonatal lung function and genetic
      susceptibility. Our aim was to investigate whether prematurely born infants were
      similarly predisposed to HRV LRTIs or any other viral LRTIs. Infants born less
      than 36 weeks of gestational age were recruited. Prior to neonatal/maternity unit
      discharge, lung function (functional residual capacity by helium gas dilution and
      multiple breath washout, lung clearance index and compliance (Crs), and
      resistance (Rrs) of the respiratory system) was assessed and DNA samples assessed
      for eight single nucleotide polymorphisms (SNPs) in seven genes: ADAM33, IL10,
      MMP16 NFkappaB1A,SFTPC, VDR, and NOS2A. Infants were prospectively followed until
      1 year corrected age. Nasopharyngeal aspirates (NPAs) were sent whenever an
      infant developed a LRTI and tested for 13 viruses. One hundred and thirty-nine
      infants were included in the analysis. Infants who developed HRV LRTIs had
      reduced Crs (1.6 versus 1.2 mL/cmH2O/kg, p = 0.044) at 36 weeks postmenstrual
      age. A SNP in the gene coding for the vitamin D receptor was associated with the
      development of HRV LRTIs and any viral LRTIs (p = 0.02). CONCLUSION: Prematurely
      born infants may have both a functional and genetic predisposition to HRV LRTIs.
      What is Known: * Term born infants are predisposed to rhinovirus lower
      respiratory tract (HRV LRTIs) infection by reduced neonatal lung function. * Term
      born infants requiring hospitalisation due to HRV bronchiolitis were more likely
      to have single nucleotide polymorphism (SNP) in the IL-10 gene. What is New: *
      Prematurely born infants who developed a HRV LRTI had lower C rs before maternity
      unit discharge. * A SNP in the gene coding for the vitamin D receptor was
      associated with the development of HRV LRTIs and overall respiratory viral LRTIs
      in prematurely born infants.

PMID- 27695991
TI  - The functional variants of endothelial nitric oxide synthase gene associated with
      rheumatoid arthritis in Turkish adults.
AB  - This study aimed to investigate whether functional variants of endothelial nitric
      oxide synthase (eNOS) gene play any role in rheumatoid arthritis (RA)
      ethiopathogenesis and treatment in the Turkish population. Because, eNOS variants
      are responsible for alteration of the NO level in plasma, by reducing/increasing
      the endothelial NO synthesis. In the study, two eNOS gene variants (G894T and
      intron 4 VNTR A/B) were examined at extracted DNAs from 65 peripheral blood cell
      of RA patients. For the control, blood samples obtained from 70 healthy persons
      were studied. Genotyping of molecular variants was performed by PCR-RFLP and/or
      PCR technique. The data obtained was compared in itself and response to therapy.
      We found that "TT genotypic frequency" for the G894T variant was significantly
      associated with RA with an overall risk of 8.3-fold (p 0.029). No association was
      identified between intron 4 VNTR A/B variant and RA. At the 6 months, the mean
      visual analog scale (VAS), health assessment questionnaire (HAQ), and disease
      activity score for 28 joints (DAS 28) improvement was not significant among
      groups. Improvement in DAS was significantly better in anti-TNF treatment than
      disease-modifying antirheumatic drugs (DMARD) treatment treated subgroup. We
      report for the first time that variants in the eNOS "TT" genotype might be
      contributed to the increased risk of RA in the Turkish population. These results
      imply that functional variants of eNOS gene might have an effect on RA patients
      and response to anti-TNF treatment. In addition, the results suggest that eNOS
      variants might be associated and affect host susceptibility and/or response to
      treatment in Turkish RA patients.

PMID- 27695992
TI  - Analysis of the blood supply to the post-fracture edentulous mandible: study by
      colour Doppler sonography.
AB  - PURPOSE: This study assessed the arterial blood supply to the mandible of
      edentulous patients treated for mandibular fractures using colour Doppler
      ultrasound. METHODS: The blood supply of edentulous patients surgically treated
      for mandibular fractures (group A) and edentulous fracture-free individuals
      (group B) was assessed. Only the fractured sides were evaluated in the first
      group (N = 17), whereas each side was evaluated in the second group (N = 20). The
      arterial flow of six sites was assessed. The systolic-peak maximum velocity
      (SPV), final diastolic velocity (FDV), resistive index (RI), pulsatility index
      (PI), acceleration and flow direction of each artery were obtained. Additionally,
      the presence of local vascular obstructive factors was evaluated. The differences
      between groups were analysed using the Kruskal-Wallis test, which was
      complemented by the Mann-Whitney test, for correlations between the degree of
      alveolar atrophy and the study factors (p < 0.050). RESULTS: There was a
      significant decrease in the flow of certain arteries, especially the submental
      (SPV, p = 0.007, PI, p = 0.022, and acceleration, p = 0.015), in the fracture
      group. The facial artery in both groups showed lower values related to local
      obstructive factors (SPV, p = 0.001, FDV, p = 0.040, and PI, p = 0.030). The
      submental artery flow was higher (SPV, p = 0.006, and FDV, p = 0.009) in non
      atrophic individuals. CONCLUSIONS: There was a decreased flow mainly in the
      submental artery, but there were no cases of major vascular injury in edentulous
      patients treated for mandibular fractures.

PMID- 27695994
TI  - Erratum to: Lysinibacillus endophyticus sp. nov., an indole-3-acetic acid
      producing endophytic bacterium isolated from corn root (Zea mays cv. Xinken-5).

PMID- 27695993
TI  - Sinorhodobacter hungdaonensis sp. nov. isolated from activated sludge collected
      from a municipal wastewater treatment plant.
AB  - A novel bacterium, strain L3T, was isolated from an activated sludge sample
      retrieved from a municipal wastewater treatment plant in Huangdao, China. On the
      basis of 16S rRNA gene sequence similarity studies, strain L3T was affiliated to
      the genus Sinorhodobacter, being most closely related to Sinorhodobacter
      ferrireducens (98.0 %). The 16S rRNA gene sequence similarity of strain L3T to
      other related species, Thioclava atlantica DLFJ1-1T (96.5 %), Rhodobacter
      capsulatus ATCC 11166T (96.3 %), Paenirhodobacter enshiensis DW2-9T (96.3 %) and
      Rhodobacter viridis JA737T (96.0 %) is less than 96.5 %. Chemotaxonomic
      characterization further supported classification of the strain to the genus
      Sinorhodobacter. The major polar lipid profile consists of diphosphatidyglycerol,
      phosphatidylglycerol and phosphatidylethanolamine. The major fatty acids are
      C18:1 omega7c (66.3 %), C16:0 (12.9 %) and C18:0 (8.0 %). The major quinone is Q
      10. The G+C content of the genomic DNA of strain L3T is 68.0 mol %. DNA-DNA
      relatedness value between L3T and the closely related type strain S.
      ferrireducens SgZ-3T was 35.2 %. Based on these results, a new species
      Sinorhodobacter huangdaonensis is proposed. The type strain is L3T (= CGMCC
      1.12963T = KCTC 42823T).

PMID- 27695995
TI  - High-throughput pyrosequencing used for the discovery of a novel cellulase from a
      thermophilic cellulose-degrading microbial consortium.
AB  - OBJECTIVES: To analyze the microbial diversity and gene content of a thermophilic
      cellulose-degrading consortium from hot springs in Xiamen, China using 454
      pyrosequencing for discovering cellulolytic enzyme resources. RESULTS: A
      thermophilic cellulose-degrading consortium, XM70 that was isolated from a hot
      spring, used sugarcane bagasse as sole carbon and energy source. DNA sequencing
      of the XM70 sample resulted in 349,978 reads with an average read length of 380
      bases, accounting for 133,896,867 bases of sequence information. The
      characterization of sequencing reads and assembled contigs revealed that most
      microbes were derived from four phyla: Geobacillus (Firmicutes), Thermus,
      Bacillus, and Anoxybacillus. Twenty-eight homologous genes belonging to 15
      glycoside hydrolase families were detected, including several cellulase genes. A
      novel hot spring metagenome-derived thermophilic cellulase was expressed and
      characterized. CONCLUSIONS: The application value of thermostable sugarcane
      bagasse-degrading enzymes is shown for production of cellulosic biofuel. The
      practical power of using a short-read-based metagenomic approach for harvesting
      novel microbial genes is also demonstrated.

PMID- 27695996
TI  - Hopf Bifurcations in Directed Acyclic Networks of Linearly Coupled Hindmarsh-Rose
      Systems.
AB  - This paper addresses the existence of Hopf bifurcations in a directed acyclic
      network of neurons, each of them being modeled by a Hindmarsh-Rose (HR) neuronal
      model. The bifurcation parameter is the small parameter corresponding to the
      ratio of time scales between the fast and the slow dynamics. We first prove that,
      under certain hypotheses, the single uncoupled neuron can undergo a Hopf
      bifurcation. Hopf bifurcation occurrences in a directed acyclic network of HR
      neurons are then discussed. Numerical simulations are carried out to observe
      these bifurcations and to illustrate the theoretical results.

PMID- 27695998
TI  - Minding the Genes: a Multidisciplinary Approach towards Genetic Assessment of
      Cardiovascular Disease.
AB  - Genetic assessment for inherited cardiovascular disease (CVD) is increasingly
      available, due in part to rapid innovations in genetic sequencing technologies.
      While genetic testing is aimed at reducing uncertainty, it also produces
      awareness of potential medical conditions and can leave patients feeling
      uncertain about their risk, especially if there are ambiguous results. This
      uncertainty can produce psychological distress for patients and their families
      undergoing the assessment process. Additionally, patients may experience
      psychological distress related to living with inherited CVD. In order to more
      effectively manage the psychosocial challenges related to genetic assessment for
      CVD, a multidisciplinary model expanded to include psychologists and other allied
      health professionals is outlined. A case study is provided to illustrate how
      psychological distress can manifest in a patient living with inherited CVD, as
      well as proposed psychological management of this patient. Finally, a guide for
      genetic counselors is provided to aid in identifying and managing common
      psychological reactions to genetic assessment for CVD.

PMID- 27695997
TI  - Early mesodermal expression of Hox genes in the polychaete Alitta virens
      (Annelida, Lophotrochozoa).
AB  - Hox genes are the key regulators of axial regionalization of bilaterian animals.
      However, their main function is fulfilled differently in the development of
      animals from different evolutionary branches. Early patterning of the developing
      embryos by Hox gene expression in the representatives of protostomes (arthropods,
      mollusks) starts in the ectodermal cells. On the contrary, the instructive role
      of the mesoderm in the axial patterning was demonstrated for vertebrates. This
      makes it difficult to understand if during the axial regionalization of ancestral
      bilaterians Hox genes first expressed in the developing mesoderm or the ectoderm.
      To resolve this question, it is necessary to expand the number of models for
      investigation of the early axial patterning. Here, we show that three Hox genes
      of the polychaete Alitta virens (formerly Nereis virens, Annelida,
      Lophotrochozoa)-Hox2, Hox4, and Lox5-are expressed in the mesodermal anlagen of
      the three future larval chaetigerous segments in spatially colinear manner before
      the initiation of Hox expression in the larval ectoderm. This is the first
      evidence of sequential Hox gene expression in the mesoderm of protostomes to
      date.

PMID- 27695999
TI  - Diversities of H-type anorectal malformation: a systematic review on a rare
      variant of the Krickenbeck classification.
AB  - Congenital H-type fistula is a rare congenital rectourogenital connection with an
      external anal opening in a normal or ectopic position. A systematic review was
      done to study the anatomical types of congenital H-type fistula, embryology,
      clinical presentation, relative gender distribution, associated anomalies,
      investigative modalities, and recent advances in treatment of these lesions. A
      PubMed search included H-type anorectal malformation; H-type anorectal
      malformations; H-type anorectal; and H-type congenital anorectal that gave
      9;43;76;26 abstracts, respectively. Relevant studies and cited articles were
      studied omitting duplicate search. The reported incidence is 0.1-16 % of all
      anorectal malformation. The H-type anorectal malformation is 2.5-6 times more
      common in females and usually associated with a normal anus. In males, the
      anomaly is usually a variant with an ectopic anus or a perineal fistula.
      Anatomical types include anovestibular; rectovestibular; rectovaginal fistula in
      females and rectourethral (bulbar, prostatic, bladder neck) and rectovesical
      fistula in males. Variants identified include H-type fistula with perineal
      fistula, perineal groove, H-type sinus, H-type canal, and acquired H-type
      fistula. This review compiles the available literature over last six decades.
      Various surgical corrective procedures have been described. The high recurrence
      decreases with a learning curve and experience.

PMID- 27696000
TI  - Modified PATIO repair for urethrocutaneous fistula post-hypospadias repair:
      operative technique and outcomes.
AB  - BACKGROUND: To describe a modification of PATIO repair for urethrocutaneous
      fistula repair and evaluate its outcome. METHODS: We studied 15 boys who
      underwent modified PATIO repair from Jan 2010 to Sept 2015. Parameters studied
      included age, type of hypospadias, age at first urethroplasty, hypospadias repair
      technique, number of urethroplasties required, location of fistula, time gap
      between urethroplasty and fistula repair, method of fistula repair, and outcome
      of fistula repair. RESULTS: Mean age of the studied patients was 67.6 months (38
      139). Type of hypospadias was Coronal = 3, subcoronal = 8, mid-penile = 2,
      prominal penile = 1, and penoscrotal = 1. Ten patients had single urethroplasty,
      while two patients had two urethroplasties, details not available for three
      patients. Average age at urethroplasty was 43.4 months (18-110). 12 patients had
      Snodgrass repair, Mathieu = 1 patient, tubularised plate repair = 1 patient, and
      unknown = 1 patient. Location of fistula was coronal in nine patients and
      subcoronal in six patients. Average operative time was 47.2 min (30-68). Follow
      up is available for 12 patients out of which 2 patients had recurrent fistula,
      one of which was successfully treated by the redo modified PATIO method.
      CONCLUSION: Modified PATIO method is technically easy method for urethrocutaneous
      fistula repair, with less operating time and good postoperative outcomes.

PMID- 27696001
TI  - Perioperative stroke after carotid endarterectomy: etiology and implications.
AB  - BACKGROUND: Carotid endarterectomy (CEA) is the procedure of choice for reducing
      the risk of stroke in both symptomatic and asymptomatic carotid artery stenoses.
      Stroke is associated with significant morbidity and mortality peri-operatively (2
      3 %). Our primary aim is to evaluate the etiology of these strokes after CEA and
      their impact on morbidity by comparing the length of stay in the hospital.
      METHODS: A total of 584 patients with documented neurological status evaluations
      who underwent CEAs were included in the study. Neurophysiological monitoring data
      was obtained during CEA for carotid stenosis included eight-channel
      electroencephalography (EEG) and upper extremity somatosensory evoked potentials
      (SSEPs). RESULTS: Twenty-one (3.595 %) patients had strokes in the perioperative
      period and they were more likely to have left-sided surgery (p = 0.008),
      intraoperative monitoring (IOM) changes (p < 0.001), an intraoperative shunt
      placed (p = 0.0002) or a hospital stay longer than 5 days (p = 0.0042).
      Unilateral anterior circulation ischemic stroke were the most common in our
      series. In a logistic regression model, left-sided surgery was shown to be 4.78
      times more likely to be associated with perioperative stroke (1.50-15.27; p =
      0.008) while intraoperative shunts were 11.85 times more likely to have strokes
      (3.97-35.34; p < 0.0001). Patients with stenosis greater than 70 % were 6.67
      times less likely to have a stroke (0.04-0.59; p = 0.007). CONCLUSIONS: Ischemic
      anterior circulation strokes are the most common type of post-operative
      neurological changes in patients undergoing CEA. Intraoperative shunt placement
      was a strong predictor of perioperative strokes. Since shunts are only placed
      following intraoperative monitoring changes, SSEPs and EEG can therefore function
      as a biomarker of cerebral hypo-perfusion.

PMID- 27696003
TI  - Temporal effects of hunting on foraging behavior of an apex predator: Do bears
      forego foraging when risk is high?
AB  - Avoiding predators most often entails a food cost. For the Scandinavian brown
      bear (Ursus arctos), the hunting season coincides with the period of hyperphagia.
      Hunting mortality risk is not uniformly distributed throughout the day, but peaks
      in the early morning hours. As bears must increase mass for winter survival, they
      should be sensitive to temporal allocation of antipredator responses to periods
      of highest risk. We expected bears to reduce foraging activity at the expense of
      food intake in the morning hours when risk was high, but not in the afternoon,
      when risk was low. We used fine-scale GPS-derived activity patterns during the 2
      weeks before and after the onset of the annual bear hunting season. At locations
      of probable foraging, we assessed abundance and sugar content, of bilberry
      (Vaccinium myrtillus), the most important autumn food resource for bears in this
      area. Bears decreased their foraging activity in the morning hours of the hunting
      season. Likewise, they foraged less efficiently and on poorer quality berries in
      the morning. Neither of our foraging measures were affected by hunting in the
      afternoon foraging bout, indicating that bears did not allocate antipredator
      behavior to times of comparably lower risk. Bears effectively responded to
      variation in risk on the scale of hours. This entailed a measurable foraging
      cost. The additive effect of reduced foraging activity, reduced forage intake,
      and lower quality food may result in poorer body condition upon den entry and may
      ultimately reduce reproductive success.

PMID- 27696005
TI  - Erratum to: Fourth cranial nerve: surgical anatomy in the subtemporal
      transtentorial approach and in the pretemporal combined inter-intradural approach
      through the fronto-temporo-orbito-zygomatic craniotomy. A cadaveric study.

PMID- 27696004
TI  - Temporal stability of reference frames in monkey area V6A during a reaching task
      in 3D space.
AB  - Neurons in the posterior parietal cortex of macaques show spatial tuning during
      several phases of an instructed delay reaching task, but their reference frames
      have been studied mostly during fixed periods without addressing how they evolve
      across task phases. In parietal area V6A, we reported recently that during the
      late delay and hand movement periods, most neurons represent target location
      either in body-centered frame of reference, or in mixed body/hand-centered
      coordinates, with no evidence of hand-centered representations. Here, we
      characterized the spatial representations of V6A neurons in earlier task epochs,
      i.e., immediately after target fixation and in the subsequent main part of the
      delay and examined whether the reference frames of individual neurons are stable
      across the task. We report no evidence of hand-centered coding also in the
      earlier phases of the task. Shortly, after target fixation and throughout the
      main part of the delay period, V6A neurons used either body-centered or mixed
      body/hand-centered reference frames. Most of the cells showed consistent
      reference frames across epochs. Interestingly, a population trend of shifting
      from mixed body/hand-centered frames to 'pure' body-centered coordinates was
      found as the task progressed. These findings suggest that, similar to other
      parietal areas, in V6A, the reference frames show a limited degree of temporal
      evolution. The stronger presence of mixed coding at the early task stages could
      reflect the early involvement of V6A in eye-hand coordination, whereas the
      increase in spatiotopic representations towards movement execution could be
      related to its role in online movement control.

PMID- 27696006
TI  - Adverse effect of high migration stress on mental health during pregnancy: a case
      report.
AB  - Despite empirical evidence on the numerous consequences associated with high
      migration stress and mental health problems during pregnancy, a psychosocial
      stress assessment is rarely done, leaving it largely unaddressed. This case
      illustration sheds light on the common multiple risk factors related to migration
      stress that have to be taken into consideration when addressing perinatal mental
      health, and highlights the importance of obstetric appointments as a unique
      opportunity to assess psychosocial stress and mobilize interdisciplinary
      interventions.

PMID- 27696002
TI  - Modelling zinc changes at the hippocampal mossy fiber synaptic cleft.
AB  - Zinc, a transition metal existing in very high concentrations in the hippocampal
      mossy fibers from CA3 area, is assumed to be co-released with glutamate and to
      have a neuromodulatory role at the corresponding synapses. The synaptic action of
      zinc is determined both by the spatiotemporal characteristics of the zinc release
      process and by the kinetics of zinc binding to sites located in the cleft area,
      as well as by their concentrations. This work addresses total, free and complexed
      zinc concentration changes, in an individual synaptic cleft, following single,
      short and long periods of evoked zinc release. The results estimate the magnitude
      and time course of the concentrations of zinc complexes, assuming that the
      dynamics of the release processes are similar to those of glutamate. It is also
      considered that, for the cleft zinc concentrations used in the model (<= 1 MUM),
      there is no postsynaptic zinc entry. For this reason, all released zinc ends up
      being reuptaken in a process that is several orders of magnitude slower than that
      of release and has thus a much smaller amplitude. The time derivative of the
      total zinc concentration in the cleft is represented by the difference between
      two alpha functions, corresponding to the released and uptaken components. These
      include specific parameters that were chosen assuming zinc and glutamate co
      release, with similar time courses. The peak amplitudes of free zinc in the cleft
      were selected based on previously reported experimental cleft zinc concentration
      changes evoked by single and multiple stimulation protocols. The results suggest
      that following a low amount of zinc release, similar to that associated with one
      or a few stimuli, zinc clearance is mainly mediated by zinc binding to the high
      affinity sites on the NMDA receptors and to the low-affinity sites on the highly
      abundant GLAST glutamate transporters. In the case of higher zinc release brought
      about by a larger group of stimuli, most zinc binding occurs essentially to the
      GLAST transporters, having the corresponding zinc complex a maximum concentration
      that is more than one order of magnitude larger than that for the high and low
      affinity NMDA sites. The other zinc complexes considered in the model, namely
      those formed with sites on the AMPA receptors, calcium and KATP channels and with
      ATP molecules, have much smaller contributions to the synaptic zinc clearance.

PMID- 27696007
TI  - Long-term linear trends mask phenological shifts.

PMID- 27696008
TI  - Erratum to: Racial disparities in all-cause mortality among younger commercially
      insured women with incident metastatic breast cancer.

PMID- 27696009
TI  - Does drug price-regulation affect healthcare expenditures?
AB  - BACKGROUND: Increasing health costs in developed countries are a major concern
      for decision makers. A variety of cost containment tools are used to control this
      trend, including maximum price regulation and reimbursement methods for health
      technologies. Information regarding expenditure-related outcomes of these tools
      is not available. OBJECTIVE: To evaluate the association between different cost
      regulating mechanisms and national health expenditures in selected countries.
      METHODS: Price-regulating and reimbursement mechanisms for prescription drugs
      among OECD countries were reviewed. National health expenditure indices for 2008
      2012 were extracted from OECD statistical sources. Possible associations between
      characteristics of different systems for regulation of drug prices and
      reimbursement and health expenditures were examined. RESULTS: In most countries,
      reimbursement mechanisms are part of publicly financed plans. Maximum price
      regulation is composed of reference-pricing, either of the same drug in other
      countries, or of therapeutic alternatives within the country, as well as value
      based pricing (VBP). No association was found between price regulation or
      reimbursement mechanisms and healthcare costs. However, VBP may present a more
      effective mechanism, leading to reduced costs in the long term. CONCLUSIONS:
      Maximum price and reimbursement mechanism regulations were not found to be
      associated with cost containment of national health expenditures. VBP may have
      the potential to do so over the long term.

PMID- 27696010
TI  - Novel Bioactive Co(II), Cu(II), Ni(II) and Zn(II) Complexes with Schiff Base
      Ligand Derived from Histidine and 1,3-Indandione: Synthesis, Structural
      Elucidation, Biological Investigation and Docking Analysis.
AB  - Novel bioactive complexes of Co(II), Cu(II), Ni(II) and Zn(II) metal ions with
      Schiff base ligand derived from histidine and 1,3-indandione were synthesized and
      thoroughly characterized by various analytical and spectral techniques. The
      biological investigations were carried out to examine the efficiency of the
      binding interaction of all the complexes with calf thymus DNA (CT-DNA). The
      binding properties were studied and evaluated quantitatively by Kb and Ksq values
      using UV-visible, fluorescence spectroscopy and voltammetric techniques. The
      experimental results revealed that the mode of binding of all the complexes with
      CT-DNA is via intercalation. It is further verified by viscosity measurements and
      thermal denaturation experiments. From the results of the cleavage study with
      pUC19 DNA it is inferred that all the complexes possess excellent cleaving
      ability. The present investigation proved that the binding interaction of all the
      complexes are significantly strong and the order of binding strength of the
      complexes is [Ni(L)2] (Kb = 3.11 * 106 M-1) > [Co(L)2] (Kb = 2.89 * 106 M-1) >
      [Cu(L)2] (Kb = 2.64 * 106 M-1) > [Zn(L)2] (Kb = 2.41 * 105 M-1). The complexes
      were also screened for antibacterial and anticandidal activity. The in vitro
      cytotoxicity of the ligand and complexes on the NIH/3 T3 mouse fibroblast cell
      lines were examined using CellTiter-Blue(r) (CTB) Cell viability assay, which
      unveiled that all the complexes exhibit more potent activities against NIH/3 T3
      cells. Among all the complexes [Zn(L)2] complex showed the maximum efficiency.

PMID- 27696011
TI  - Comparative evaluation of two Rickettsia typhi-specific quantitative real-time
      PCRs for research and diagnostic purposes.
AB  - Rickettsioses are caused by intracellular bacteria of the family of
      Rickettsiaceae. Rickettsia (R.) typhi is the causative agent of endemic typhus.
      The disease occurs worldwide and is one of the most prevalent rickettsioses.
      Rickettsial diseases, however, are generally underdiagnosed which is mainly due
      to the lack of sensitive and specific methods. In addition, methods for
      quantitative detection of the bacteria for research purposes are rare. We
      established two qPCRs for the detection of R. typhi by amplification of the outer
      membrane protein B (ompB) and parvulin-type PPIase (prsA) genes. Both qPCRs are
      specific and exclusively recognize R. typhi but no other rickettsiae including
      the closest relative, R. prowazekii. The prsA-based qPCR revealed to be much more
      sensitive than the amplification of ompB and provided highly reproducible results
      in the detection of R. typhi in organs of infected mice. Furthermore, as a nested
      PCR the prsA qPCR was applicable for the detection of R. typhi in human blood
      samples. Collectively, the prsA-based qPCR represents a reliable method for the
      quantitative detection of R. typhi for research purposes and is a promising
      candidate for differential diagnosis.

PMID- 27696012
TI  - Intermittent vs. Continuous Anticoagulation theRapy in patiEnts with Atrial
      Fibrillation (iCARE-AF): a randomized pilot study.
AB  - PURPOSE: We hypothesized that intermittent anticoagulation based on daily rhythm
      monitoring using the novel oral anticoagulants (NOACs) is feasible and safe among
      patients with paroxysmal atrial fibrillation (AF). METHODS: Patients with
      paroxysmal AF and >=1 risk factors for stroke were randomized to either
      intermittent or continuous anticoagulation. Those in the intermittent group were
      instructed to transmit a daily ECG using an iPhone-based rhythm monitoring
      device. If AF was detected, patients received one of the NOACs for 48 h-1 week.
      Patients who failed to transmit an ECG for three consecutive days or more than 7
      days total were crossed over to continuous anticoagulation. Patients in the
      continuous group received one of the NOACs. RESULTS: Fifty-eight patients were
      randomized to either intermittent (n = 29) or continuous anticoagulation (n =
      29). Over a median follow-up of 20 months, 20 patients in the intermittent group
      failed to submit a daily ECG at least once (median three failed submissions).
      Four patients (14 %) crossed over to continuous anticoagulation due to failure to
      submit an ECG for three consecutive days. One stroke (continuous group) occurred
      during the study. Major bleeding occurred in two patients in the continuous and
      one patient in the intermittent group, after crossing over to continuous
      anticoagulation. In a prespecified per-protocol analysis, gastrointestinal
      bleeding was more frequent in the continuous group (16 vs. 0 %; p = 0.047).
      CONCLUSIONS: Intermittent anticoagulation based on daily rhythm monitoring is
      feasible and may decrease bleeding in low-risk patients with paroxysmal AF. A
      larger trial, adequately powered to detect clinical outcomes, is warranted.

PMID- 27696013
TI  - Ultrasound findings of diffuse metastasis of gastric signet-ring-cell carcinoma
      to the thyroid gland.
AB  - It has been shown that metastases to the thyroid from extrathyroidal malignancies
      occur as solitary or multiple nodules, or may involve the whole thyroid gland
      diffusely. However, diffuse metastasis of gastric cancer to the thyroid is
      extremely rare. Here, we report a case of a 74-year-old woman with diffuse
      infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly
      differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis
      was made based on upper gastrointestinal endoscopy with biopsy and fine-needle
      aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions
      with increased uptake, including the bilateral thyroid gland. On thyroid
      ultrasound examination, diffuse enlargement with internal heterogeneity and
      hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow
      signal was not detected in these hypoechoic lines. These findings were similar to
      those of diffuse metastases caused by other primary cancers, such as lung cancer,
      as reported earlier. Therefore, the presence of hypoechoic reticular lines
      without blood-flow signals is probably common to diffuse thyroid metastasis from
      any origin and an important diagnostic finding. This is the first report to show
      detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid
      gland using color Doppler.

PMID- 27696014
TI  - Expression pattern of HSFY in the mouse testis and epididymis with and without
      heat stress.
AB  - Heat shock factors (HSFs) are critical regulators of spermatogenesis. However,
      heat shock responses, the associated components and the underlying functional
      mechanisms remain to be elucidated. Here, we characterize the expression pattern
      of HSFY, a member of the HSF family in the testis and epididymis. Its expression
      in testis and epididymis was initially identified by western blots.
      Immunofluorescence staining demonstrated that HSFY was confined to the cytoplasm
      of late spermatocytes and spermatids in adult testes, gonocytes in newborn testes
      and undifferentiated spermatogonia in 7 days post-parturition testes. In the
      epididymis, HSFY was predominantly expressed in principal cells. Furthermore, a
      single transient scrotal heat stress did not change HSFY protein expression in
      the testes or epididymis, either on the expressional level or in cellular
      localization. In summary, this study detected the expression pattern of HSFY in
      the testes and epididymis and demonstrated that its expression was not regulated
      by transient elevated temperature.

PMID- 27696016
TI  - Perspective: parameters in a self-consistent field theory of multicomponent
      wormlike-copolymer melts.
AB  - We review a formalism that can be used to calculate the microphase-separated
      crystallographic structures of multi-component wormlike polymer melts. The
      approach is based on a self-consistent field theory of wormlike polymers where
      the persistence length of each component is an important parameter. We emphasize
      on an analysis of the number of independent parameters required to specify a
      problem in general, for a system that includes Flory-Huggins and Maier-Saupe
      energies. Examples of recent applications are also briefly demonstrated: AB
      homopolymer interface, AB diblock copolymers, and rod-coil copolymers.

PMID- 27696015
TI  - A neurodegenerative perspective on mitochondrial optic neuropathies.
AB  - Mitochondrial optic neuropathies constitute an important cause of chronic visual
      morbidity and registrable blindness in both the paediatric and adult population.
      It is a genetically heterogeneous group of disorders caused by both mitochondrial
      DNA (mtDNA) mutations and a growing list of nuclear genetic defects that
      invariably affect a critical component of the mitochondrial machinery. The two
      classical paradigms are Leber hereditary optic neuropathy (LHON), which is a
      primary mtDNA disorder, and autosomal dominant optic atrophy (DOA) secondary to
      pathogenic mutations within the nuclear gene OPA1 that encodes for a
      mitochondrial inner membrane protein. The defining neuropathological feature is
      the preferential loss of retinal ganglion cells (RGCs) within the inner retina
      but, rather strikingly, the smaller calibre RGCs that constitute the
      papillomacular bundle are particularly vulnerable, whereas melanopsin-containing
      RGCs are relatively spared. Although the majority of patients with LHON and DOA
      will present with isolated optic nerve involvement, some individuals will also
      develop additional neurological complications pointing towards a greater
      vulnerability of the central nervous system (CNS) in susceptible mutation
      carriers. These so-called "plus" phenotypes are mechanistically important as they
      put the loss of RGCs within the broader perspective of neuronal loss and
      mitochondrial dysfunction, highlighting common pathways that could be modulated
      to halt progressive neurodegeneration in other related CNS disorders. The
      management of patients with mitochondrial optic neuropathies still remains
      largely supportive, but the development of effective disease-modifying treatments
      is now within tantalising reach helped by major advances in drug discovery and
      delivery, and targeted genetic manipulation.

PMID- 27696018
TI  - The Therapist's Role in Effective Marriage and Family Therapy Practice: The Case
      for Evidence Based Therapists.
AB  - In this paper we argue that the therapist is a crucial change variable in
      psychotherapy as a whole and in couple, marital, and family therapy specifically.
      Therapists who work with complex systems require more skills to negotiate
      demanding therapy contexts. Yet, little is known about what differentiates
      effective couple, marital, and family therapists from those who are less
      effective, what innate therapy skills they possess, how they learn, and how they
      operationalize their knowledge in the therapy room. We discuss the need to
      emphasize evidence based therapists (as opposed to therapies), and implications
      of the importance of the role therapists for training, practice, research
      priorities, and policy.

PMID- 27696019
TI  - Caretaking through Art: A Sibling Story.

PMID- 27696017
TI  - A randomized placebo-blind study of the effect of low power laser on pain caused
      by irreversible pulpitis.
AB  - This randomized placebo-blind study aimed to evaluate the effect of laser
      phototherapy (LPT) on pain caused by symptomatic irreversible pulpitis (SIP).
      Sixty patients diagnosed with SIP were randomly assigned to treatment groups (n =
      15): G1 (control), G2 (laser placebo-sham irradiation), G3 (laser irradiation at
      780 nm, 40 mW, 4 J/cm2), and G4 (laser irradiation at 780 nm, 40 mW, 40 J/cm2).
      Spontaneous pain was recorded using a VAS score before (T0), immediately after
      (T1), and 15 min after treatment (T2). Local anesthetics failure during emergency
      endodontic treatment was also assessed. There was no pain difference in T1 and T2
      between the experimental laser groups (G3 and G4) and the placebo group (G2). The
      4-J/cm2 (G3) irradiation resulted in significant increase in the local
      anesthetics failure in lower jar teeth. This effect could be suggested as
      consequence of the LPT improvement in local circulation and vasodilatation that
      would result in the increase of local anesthetic agent absorption. The
      application of 780-nm diode laser irradiation, at 4 and 40 J/cm2, showed no
      effect in reducing the pain in SIP in comparison to the placebo group. The
      fluence of 4 J/cm2 showed a negative effect in local anesthetics, resulting in
      significant increase of complimentary local anesthesia during emergency
      endodontic treatment. This work provides evidence of the consequence of LPT
      application on teeth with symptomatic irreversible pulpitis. LPT should be
      avoided in teeth with pain due to irreversible pulpitis.

PMID- 27696020
TI  - Morphological and ultrastructural characterization of the acidophilic and lipid
      producer strain Chlamydomonas acidophila LAFIC-004 (Chlorophyta) under different
      culture conditions.
AB  - Chlamydomonas acidophila LAFIC-004 is an acidophilic strain of green microalgae
      isolated from coal mining drainage. In the present work, this strain was
      cultivated in acidic medium (pH 3.6) under phototrophic, mixotrophic, and
      heterotrophic regimes to determine the best condition for growth and lipid
      production, simultaneously assessing possible morphological and ultrastructural
      alterations in the cells. For heterotrophic and mixotrophic treatments, two
      organic carbon sources were tested: 1 % glucose and 1 % sodium acetate. Lipid
      content and fatty acid profiles were only determined in phototrophic condition.
      The higher growth rates were achieved in phototrophic conditions, varying from
      0.18 to 0.82 day-1. Glucose did not result in significant growth increase in
      either mixotrophic or heterotrophic conditions, and acetate proved to be toxic to
      the strain in both conditions. Oil content under phototrophic condition was 15.9
      % at exponential growth phase and increased to 54.63 % at stationary phase. Based
      on cell morphology (flow cytometry and light microscopy) and ultrastructure
      (transmission electron microscopy), similar characteristics were observed between
      phototrophic and mixotrophic conditions with glucose evidencing many lipid
      bodies, starch granules, and intense fluorescence. Under the tested conditions,
      mixotrophic and heterotrophic modes did not result in increased neutral lipid
      fluorescence. It can be concluded that the strain is a promising lipid producer
      when grown until stationary phase in acidic medium and under a phototrophic
      regime, presenting a fatty acid profile suitable for biodiesel production. The
      ability to grow this strain in acidic mining residues suggests a potential for
      bioremediation with production of useful biomass.

PMID- 27696021
TI  - N,N-dimethyl hexadecylamine and related amines regulate root morphogenesis via
      jasmonic acid signaling in Arabidopsis thaliana.
AB  - Plant growth-promoting rhizobacteria are natural inhabitants of roots, colonize
      diverse monocot and dicot species, and affect several functional traits such as
      root architecture, adaptation to adverse environments, and protect plants from
      pathogens. N,N-dimethyl-hexadecylamine (C16-DMA) is a rhizobacterial amino lipid
      that modulates the postembryonic development of several plants, likely as part of
      volatile blends. In this work, we evaluated the bioactivity of C16-DMA and other
      related N,N-dimethyl-amines with varied length and found that inhibition of
      primary root growth was related to the length of the acyl chain. C16-DMA
      inhibited primary root growth affecting cell division and elongation, while
      promoting lateral root formation and root hair growth and density in Arabidopsis
      thaliana (Arabidopsis) wild-type (WT) seedlings. Interestingly, C16-DMA induced
      the expression of the jasmonic acid (JA)-responsive gene marker pLOX2:uidA, while
      JA-related mutants jar1, coi1-1, and myc2 affected on JA biosynthesis and
      perception, respectively, are compromised in C16-DMA responses. Comparison of
      auxin-regulated gene expression, root architectural changes in WT, and auxin
      related mutants aux1-7, tir1/afb2/afb3, and arf7-1/arf19-1 to C16-DMA shows that
      the C16-DMA effects occur independently of auxin signaling. Together, these
      results reveal a novel class of aminolipids modulating root organogenesis via
      crosstalk with the JA signaling pathway.

PMID- 27696022
TI  - Propofol Inhibits NLRP3 Inflammasome and Attenuates Blast-Induced Traumatic Brain
      Injury in Rats.
AB  - Increasing evidence has demonstrated that inflammatory response plays a crucial
      role in the pathogenesis of secondary injury following blast-induced traumatic
      brain injury (bTBI). Propofol, a lipid-soluble intravenous anesthetic, has been
      shown to possess therapeutic benefit during neuroinflammation on various brain
      injury models. Recent findings have proved that the NOD-like receptor family,
      pyrin domain-containing 3 (NLRP3) inflammasome involved in the process of the
      inflammatory response following brain trauma, may probably be a promising target
      in the treatment of bTBI. Rats were randomly divided into six groups (n = 8):
      normal group; bTBI-12 and 24 h group; bTBI-12 h and bTBI-24 h group treated with
      propofol; and bTBI treated with control dimethyl sulfoxide (DMSO) group. The
      effect of propofol on the expression and activation of NLRP3 inflammasome and the
      degree of oxidative stress and inflammatory cascades, as well as the brain trauma
      biomarkers were evaluated in rats suffering from bTBI. The enhanced expressions
      and activation of NLRP3 inflammasome in the cerebral cortex of bTBI rats were
      substantially suppressed by the administration of propofol, which was paralleled
      with the decreased oxidative stress, cytokines production, and the amelioration
      of cerebral cortex damage. Our results have, for the first time, revealed that
      over-activation of NLRP3 inflammasome in the cerebral cortex may be involved in
      the process of neuroinflammation during the secondary injury of bTBI in rats.
      Propofol might relieve the inflammatory response and attenuate brain injury by
      inhibiting ROS and reluctant depressing NLRP3 inflammasome activation and pro
      inflammatory cytokines maturation.

PMID- 27696024
TI  - ?

PMID- 27696025
TI  - ?

PMID- 27696023
TI  - Bioproduction of riboflavin: a bright yellow history.
AB  - Riboflavin (vitamin B2) is an essential nutrient for humans and animals that must
      be obtained from the diet. To ensure an optimal supply, riboflavin is used on a
      large scale as additive in the food and feed industries. Here, we describe a
      historical overview of the industrial process of riboflavin production starting
      from its discovery and the need to produce the vitamin in bulk at prices that
      would allow for their use in human and animal nutrition. Riboflavin was produced
      industrially by chemical synthesis for many decades. At present, the development
      of economical and eco-efficient fermentation processes, which are mainly based on
      Bacillus subtilis and Ashbya gossypii strains, has replaced the synthetic process
      at industrial scale. A detailed account is given of the development of the
      riboflavin overproducer strains as well as future prospects for its improvement.

PMID- 27696026
TI  - ?

PMID- 27696027
TI  - ?

PMID- 27696028
TI  - ?
AB  - The prevalence of cerebral palsy (CP) has increased over the last 15 years in
      most countries. This is explained by an improved survival of very low birth
      weight prematures. In term infants birth asphyxia is of minor significance as a
      cause for CP. In only 10% of all CP cases following delivery at term, birth
      asphyxia must be discussed as a possible cause. In premature deliveries events
      during the perinatal period are of greater significance for the later development
      of a CP. Only severe forms of oxygen deficit, leading to tissue damage in the
      brain and other organs with clinical symptoms during the first days of life, are
      of significance for the long term prognosis. Even in the presence of severe birth
      asphyxia the causal relationship with a psychomotor handicap is not proven, since
      brain damage may have developed during pregnancy before the onset of labour and
      may be the cause of birth asphyxia. Brain damage and birth asphyxia may be the
      result of a common pathology of pregnancy.

PMID- 27696029
TI  - ?

PMID- 27696030
TI  - ?

PMID- 27696031
TI  - ?

PMID- 27696033
TI  - ?

PMID- 27696032
TI  - ?

PMID- 27696034
TI  - ?

PMID- 27696035
TI  - ?

PMID- 27696036
TI  - ?

PMID- 27696037
TI  - ?

PMID- 27696039
TI  - ?

PMID- 27696038
TI  - ?

PMID- 27696041
TI  - ?

PMID- 27696042
TI  - ?

PMID- 27696040
TI  - ?

PMID- 27696043
TI  - ?

PMID- 27696045
TI  - ?

PMID- 27696047
TI  - ?

PMID- 27696046
TI  - ?

PMID- 27696048
TI  - ?

PMID- 27696049
TI  - ?

PMID- 27696050
TI  - ?

PMID- 27696051
TI  - ?

PMID- 27696052
TI  - ?

PMID- 27696053
TI  - ?

PMID- 27696054
TI  - ?

PMID- 27696055
TI  - ?

PMID- 27696056
TI  - ?

PMID- 27696057
TI  - ?

PMID- 27696058
TI  - ?

PMID- 27696059
TI  - ?

PMID- 27696060
TI  - ?

PMID- 27696061
TI  - ?

PMID- 27696062
TI  - ?

PMID- 27696063
TI  - ?

PMID- 27696064
TI  - ?

PMID- 27696065
TI  - ?

PMID- 27696066
TI  - ?

PMID- 27696067
TI  - ?

PMID- 27696068
TI  - Cardiac dysfunction in type II diabetes: a bittersweet, weighty problem, or both?
AB  - AIMS: Weight loss in obese patients leads to improved left ventricular (LV)
      function. It is unclear whether improving glycaemic control has additional
      benefits to weight loss alone in patients with type 2 diabetes, or if benefits of
      weight loss are mediated through improving glycaemic control. This case-control
      study examined the incremental impact of these approaches on LV function.
      METHODS: Three groups of age, gender, and baseline HbA1c-matched patients with
      type 2 diabetes and suboptimal glycaemic control were followed-up for 12 months.
      Group 1 patients did not improve HbA1c >= 1 % (10.9 mmol/mol) or lose weight.
      Group 2 improved HbA1c >= 1 % but did not lose weight. Group 3 improved HbA1c >=
      1 % (10.9 mmol/mol) and lost weight. All patients underwent transthoracic
      echocardiogram at baseline and at follow-up. RESULTS: At baseline, three groups
      were comparable in all clinical and metabolic parameters except Group 3 had
      highest body mass index. The three groups had similar echocardiographic
      parameters except Group 3 had the worst LV systolic function [global longitudinal
      strain (GLS)]. At follow-up, LV ejection fraction and diastolic function improved
      with a reduction in filling pressures in Group 2 and more so in Group 3. LV
      filling pressures in Group 1 increased. There was a significant improvement in
      GLS in Group 2 and more so in Group 3. Despite GLS being the worst in Group 3 at
      baseline, this was comparable between Groups 2 and 3 at follow-up. CONCLUSIONS:
      In overweight patients with type 2 diabetes, weight loss and improved glycaemic
      control had additive beneficial effects on improving LV systolic and diastolic
      function.

PMID- 27696069
TI  - Investigation of the relationship between hemoglobin and serum iron levels and
      early-phase insulin secretion in non-diabetic subjects: statistical and
      methodological issues.

PMID- 27696070
TI  - MicroRNA-126 and micro-/macrovascular complications of type 1 diabetes in the
      EURODIAB Prospective Complications Study.
AB  - AIMS: Increasing evidence suggests a potential role of circulating miRNAs as
      clinical biomarkers, and loss of miRNA-126 has been proposed as a predictor of
      type 2 diabetes onset. However, a systematic analysis of circulating miRNAs in
      type 1 diabetic patients with micro-/macrovascular complications has not yet been
      performed. METHODS: A cross-sectional nested case-control study from the EURODIAB
      Prospective Complications Study of 455 type 1 diabetic patients was performed.
      Case subjects (n = 312) were defined as those with one or more complications of
      diabetes; control subjects (n = 143) were those with no evidence of any
      complication. A differential miRNA expression profiling was performed in pooled
      serum samples from cases and controls. Furthermore, miR-126 levels were
      quantified by qPCR in all individual samples and associations with diabetic
      complications investigated. RESULTS: Twenty-five miRNAs differed in pooled
      samples from cases and controls. miR-126 levels were significantly lower in case
      than in control subjects, even after adjustment for age and sex. In logistic
      regression analyses, miR-126 was negatively associated with all complications (OR
      = 0.85, 95 % CI 0.75-0.96) as well as with each micro-/macrovascular complication
      examined separately. This was likely dependent of diabetes as associations were
      no longer significant after adjustment for both hyperglycemia and diabetes
      duration. However, a significant 25 % risk reduction, independent of age, sex,
      A1C, and diabetes duration, was still observed for proliferative retinopathy (OR
      = 0.75, 95 % CI 0.59-0.95). CONCLUSIONS: In this large cohort of type 1 diabetic
      subjects, we found that miR-126 levels are associated with vascular complications
      of diabetes, particularly with proliferative retinopathy.

PMID- 27696071
TI  - Treatment of diabetic gastroparesis with botulinum toxin injection guided by
      endoscopic ultrasound in a patient with type 1 diabetes: the first report.

PMID- 27696072
TI  - Sex ratio at birth is associated with type 1 diabetes characteristics.
AB  - AIMS: To assess the association between maternal diabetes characteristics and sex
      ratio at birth (SRB) in women with type 1 diabetes mellitus. METHODS: We
      performed a case-control study. The study subjects were infants born alive to
      women with type 1 diabetes and singleton pregnancies. Cases and controls were
      defined as male and female newborns, respectively. SRB was analysed according to
      diabetes-related characteristics adjusting in a logistic regression analysis for
      maternal characteristics known to affect SRB in the general population. RESULTS:
      The observed SRB (238 males/468 live births = 0.509) did not differ from the
      expected. In the logistic regression analysis, SRB was significantly associated
      with three diabetes characteristics: (1) diabetes duration, with odds ratios
      (ORs) for a live male newborn = 1.22 (95 % confidence interval (CI), 0.66-2.24
      for <=5 years, OR 2.79 (95 % CI 1.36-5.74) for >20 years; (2) mean first
      trimester glycated haemoglobin, with OR 1.98 (95 % CI 1.09-3.62) for <=6.7 % (50
      mmol/mol) and OR 2.61 (95 % CI 1.16-5.85) for >8.2 % (66 mmol/mol) and (3) mean
      first-trimester insulin dose, with OR 0.70 (95 % CI 0.36-1.38) for <=0.5
      IU/kg/day and OR 0.18 (95 % CI 0.05-0.59) for >1.0 IU/kg/day. CONCLUSIONS: We
      conclude that SRB in this cohort is independently associated with three diabetes
      characteristics. These associations are to be confirmed.

PMID- 27696073
TI  - The influence of bottom boundary layer hydrodynamics on sediment focusing in a
      contaminated bay.
AB  - Understanding the dynamics and fate of particle bound contaminants is important
      for mitigating potential environmental, economic and health impacts linked to
      their presence. Vidy Bay, Lake Geneva (Switzerland), is contaminated due to the
      outfall and overflow from the wastewater treatment plant of the City of Lausanne.
      This study was designed to investigate the fate of particle-bound contaminants
      with the goal of providing a more complete picture of contaminant pathways within
      the bay and their potential spread to the main basin. This goal was achieved by
      investigating the sediment transport dynamics, using sediment traps and
      radionuclide tracers, and ascertaining how local bottom-boundary hydrodynamic
      conditions (temperature, turbidity, current velocity and direction) influence
      these dynamics. Results of the study indicated that sedimentation rates and
      lateral advections increased vertically with proximity to the lakebed and
      laterally with proximity to shore, indicating the presence of sediment focusing
      in the bay. Hydrodynamic measurements showed the persistent influence of a gyre
      within the bay, extending down to the lake bed, while just outside of the bay
      circulation was influenced by the seasonal patterns of the main basin. Calculated
      mean displacement distances in the bay indicated that suspended particles can
      travel ~3 km per month, which is 1.7 times the width of the Vidy Bay gyre. This
      results in a residence time of approximately 21 days for suspended particles,
      which is much greater than previously modelled results. The calculated mobility
      Shield parameter never exceeded the threshold shear stress needed for
      resuspension in deeper parts of the bay. In such, increased lateral advections to
      the bay are not likely due to local resuspension but rather external particle
      sources, such as main basin or shallow, littoral resuspensions. These external
      sources coupled with an increased residence time and decreased current velocity
      within the bay are the precipitating factors in sediment focusing. While the
      spread of contaminants from the bay may occur through the transport of fine
      suspended sediments in shallower zones of the bay (<60 m) by longshore littoral
      currents, results suggest that particle-bound contaminants are likely to remain
      within the bay.

PMID- 27696075
TI  - Capsule Commentary on Howell et al., Incarceration History and Uncontrolled Blood
      Pressure in a Multi-Site Cohort.

PMID- 27696074
TI  - Occurrence of pharmaceuticals in WWTP effluents and their impact in a karstic
      rural catchment of Eastern France.
AB  - The occurrence of pharmaceuticals in freshwater ecosystems provokes increasing
      concern due to their potential risk to non-target organisms and to human health.
      Pharmaceuticals are used in both human and veterinary medicine and are
      essentially released into the environment via wastewater treatment plants (WWTPs)
      and from livestock. In this study, 31 pharmaceuticals were analyzed in effluent
      and surface water upstream and downstream of two WWTPs in the Loue-Doubs rural
      karstic catchment in Eastern France. Diclofenac (965 and 2476 ng L-1),
      sulfamethoxazole (655 and 1380 ng L-1) and carbamazepine (566 and 1007 ng L-1)
      displayed the highest levels in the effluents of both WWTPs. Diclofenac levels
      were also high in surface water samples 300 and 166 ng L-1 in the River Doubs and
      the River Loue, respectively, followed by paracetamol (273 and 158 ng L-1) and
      sulfamethoxazole (126 and 73 ng L-1). In both rivers, the most critical compounds
      were found to be the antibiotic sulfamethoxazole (risk quotient (RQ) from 23.7 to
      51.1) and ofloxacine (RQ from 1.1 to 18.9), which reached levels inducing toxic
      effects in aquatic organisms. This study showed that WWTP effluents are the major
      sources of the pharmaceuticals, but raw discharges from human residences,
      pastures and livestock manure represent significant sources of contamination of
      surface water and groundwater. The aim of this study was to assist scientists and
      authorities in understanding occurrence and sources of pharmaceuticals in order
      to improve water quality management in chalk streams.

PMID- 27696076
TI  - Characterization of miRNAs responsive to exogenous ethylene in grapevine berries
      at whole genome level.
AB  - MicroRNAs (miRNAs) are critical regulators of various biological and metabolic
      processes of plants. Numerous miRNAs and their functions have been identified and
      analyzed in many plants. However, till now, the involvement of miRNAs in the
      response of grapevine berries to ethylene has not been reported yet. Here, Solexa
      technology was employed to deeply sequence small RNA libraries constructed from
      grapevine berries treated with and without ethylene. A total of 124 known and 78
      novel miRNAs were identified. Among these miRNAs, 162 miRNAs were clearly
      responsive to ethylene, with 55 downregulated, 59 upregulated, and 14 unchanged
      miRNAs detected only in the control. The other 35 miRNAs responsive to ethylene
      were induced by ethylene and detected only in the ethylene-treated grapevine
      materials. Expression analysis of 27 conserved and 26 novel miRNAs revealed that
      13 conserved and 18 novel ones were regulated by ethylene during the whole
      development of grapevine berries. High-throughput sequencing and qRT-PCR assays
      revealed consistent results on the expression results of ethylene-responsive
      miRNAs. Moreover, 90 target genes for 34 novel miRNAs were predicted, most of
      which were involved in responses to various stresses, especially like exogenous
      ethylene treatment. The identified miRNAs may be mainly involved in grapevine
      berry development and response to various environmental conditions.

PMID- 27696077
TI  - Differences in sleep habits, study time, and academic performance between US-born
      and foreign-born college students.
AB  - PURPOSE: To inform the design of a sleep improvement program for college
      students, we assessed academic performance, sleep habits, study hours, and
      extracurricular time, hypothesizing that there would be differences between US
      born and foreign-born students. METHODS: Questionnaires queried participants on
      bedtimes, wake times, nap frequency, differences in weekday and weekend sleep
      habits, study hours, grade point average, time spent at paid employment, and
      other extracurricular activities. Comparisons were made using chi square tests
      for categorical data and t tests for continuous data between US-born and foreign
      born students. RESULTS: Of 120 participants (55 % women) with racial diversity
      (49 whites, 18 blacks, 26 Hispanics, 14 Asians, and 13 other), 49 (41 %) were
      foreign-born. Comparisons between US-born and foreign-born students showed no
      differences in average age or gender though US-born had more whites. There were
      no differences between US-born and foreign-born students for grade point
      averages, weekday bedtimes, wake times, or total sleep times. However, US-born
      students averaged 50 min less study time per day (p = 0.01), had almost 9 h less
      paid employment per week (14.5 vs 23.4 h per week, p = 0.001), and stayed up to
      socialize more frequently (63 vs 43 %, p = 0.03). Foreign-born students awakened
      an hour earlier and averaged 40 min less sleep per night on weekends.
      CONCLUSIONS: Cultural differences among college students have a profound effect
      on sleep habits, study hours, and extracurricular time. The design of a sleep
      improvement program targeting a population with diverse cultural backgrounds must
      factor in such behavioral variations in order to have relevance and impact.

PMID- 27696078
TI  - Quality of life (QOL) and symptom burden (SB) in patients with breast cancer.
AB  - PURPOSE: The purpose of this study was to determine the quality of life (QOL) and
      symptom burden (SB) among breast cancer patients. METHODS: Patients with DCIS,
      early stage, locally advanced, or metastatic breast cancer completed the Edmonton
      Symptom Assessment System (ESAS) and the Functional Assessment of Cancer Therapy
      for Breast Cancer (FACT-B). Patients were divided into subsequent cohorts based
      on their last day of treatment, age at enrollment, radiation, chemotherapy, and
      hormone therapy. RESULTS: A total of 1513 patients were enrolled. Metastatic
      patients had a lower QOL and greatest SB compared to all other patient groups.
      Patients <=50 years old with early stage or locally advanced breast cancer had a
      lower QOL and greater SB for fatigue, depression, and anxiety compared to all
      other age cohorts. Patients with early stage breast cancer who received
      chemotherapy had a lower QOL and greater SB. Patients taking selective estrogen
      receptor modulator (SERM) had greater SB for depression and lower QOL compared to
      those not on SERM. Patients 2-10 years post-treatment had a lower QOL compared to
      patients >=10 years post-treatment. CONCLUSION: Patients <=50 years old, 2-10
      years post-treatment, treated with chemotherapy or SERM had increased SB and
      decreased QOL. Individualized interventions and programs can be developed to
      tailor to physical, educational, and psychosocial needs identified across the
      breast cancer continuum.

PMID- 27696080
TI  - Determining protein biomarkers for DLBCL using FFPE tissues from HIV negative and
      HIV positive patients.
AB  - DLBCL is the most common lymphoma subtype occurring in older populations as well
      as in younger HIV infected patients. The current treatment options for DLBCL are
      effective for most patients yet the relapse rate is high. While many biomarkers
      for DLBCL exist, they are not in clinical use due to low sensitivity and
      specificity. In addition, these biomarkers have not been studied in the HIV
      context. Therefore, the identification of new biomarkers for HIV negative and HIV
      positive DLBCL, may lead to a better understanding of the disease pathology and
      better therapeutic design. Protein biomarkers for DLBCL were determined using
      MALDI imaging mass spectrometry (IMS) and characterised using LC-MS. The
      expression of one of the biomarkers, heat shock protein (Hsp) 70, was confirmed
      on a separate cohort of samples using immunohistochemistry. The biomarkers
      identified in the study consisted of four protein clusters including glycolytic
      enzymes, ribosomal proteins, histones and collagen. These proteins could
      differentiate between control and tumour tissue, and the DLBCL
      immunohistochemical subtypes in both cohorts. The majority (41/52) of samples in
      the confirmation cohort were negative for Hsp70 expression. The HIV positive
      DLBCL cases had a higher percentage of cases expressing Hsp70 than their HIV
      negative counterparts. The non-GC subtype also frequently overexpressed Hsp70,
      confirming MALDI IMS data. The expression of Hsp70 did not correlate with
      survival in both the HIV negative and HIV positive cohort. This study identified
      potential biomarkers for HIV negative and HIV positive DLBCL from FFPE tissue
      sections. These may be used as diagnostic and prognostic markers complementary to
      current clinical management programmes for DLBCL.

PMID- 27696081
TI  - Tyrosine Hydroxylase Expression in Type II Cochlear Afferents in Mice.
AB  - Acoustic information propagates from the ear to the brain via spiral ganglion
      neurons that innervate hair cells in the cochlea. These afferents include
      unmyelinated type II fibers that constitute 5 % of the total, the majority being
      myelinated type I neurons. Lack of specific genetic markers of type II afferents
      in the cochlea has been a roadblock in studying their functional role.
      Unexpectedly, type II afferents were visualized by reporter proteins induced by
      tyrosine hydroxylase (TH)-driven Cre recombinase. The present study was designed
      to determine whether TH-driven Cre recombinase (TH-2A-CreER) provides a selective
      and reliable tool for identification and genetic manipulation of type II rather
      than type I cochlear afferents. The "TH-2A-CreER neurons" radiated from the
      spiral lamina, crossed the tunnel of Corti, turned towards the base of the
      cochlea, and traveled beneath the rows of outer hair cells. Neither the processes
      nor the somata of TH-2A-CreER neurons were labeled by antibodies that
      specifically labeled type I afferents and medial efferents. TH-2A-CreER-positive
      processes partially co-labeled with antibodies to peripherin, a known marker of
      type II afferents. Individual TH-2A-CreER neurons gave off short branches
      contacting 7-25 outer hair cells (OHCs). Only a fraction of TH-2A-CreER boutons
      were associated with CtBP2-immunopositive ribbons. These results show that TH-2A
      CreER provides a selective marker for type II versus type I afferents and can be
      used to describe the morphology and arborization pattern of type II cochlear
      afferents in the mouse cochlea.

PMID- 27696082
TI  - The association between China's Great famine and risk of breast cancer according
      to hormone receptor status: a hospital-based study.
AB  - PURPOSE: The Great Chinese Famine afflicted almost all Chinese people between
      1959 and 1961. No study has explicitly assessed the association between an
      exposure to Chinese Famine and risk of overall breast cancer and tumor subtype.
      We evaluated the unique historical environmental influences of famine exposure on
      breast cancer subtypes. METHODS: 16,469 Chinese women who were diagnosed with
      invasive breast cancer in the Fudan University Shanghai Cancer Center (FUSCC)
      from 1999 to 2014 were analyzed. Four tumor subtypes were defined by both
      estrogen-receptor (ER) and progesterone-receptor (PR) status. Multinomial
      logistic regression models were used to estimate the odds ratios (ORs) of ER-PR-,
      ER+PR-, and ER-PR+ relative to ER+PR+ breast cancer for exposure to famine and
      age at the exposure. RESULTS: Compared with cases not exposed to the Famine,
      exposed cases were more likely to be diagnosed with ER-PR- (OR 1.60, 95 % CI 1.43
      1.81), ER-PR+ (OR 4.85, 95 % CI 3.80-6.19), and ER+PR- (OR 1.99, 95 % CI 1.67
      2.37) than ER+PR+ breast cancer after controlling for established breast cancer
      risk factors. Women exposed to Famine after first birth had a higher risk of EP
      PR- (OR 1.66, 95 % CI 1.28-2.15), ER-PR+ (OR 9.75, 95 % CI 5.85-16.25), and ER+PR
      (OR 2.35, 95 % CI 1.69-3.26) compared to those with ER+PR+ breast cancer.
      CONCLUSIONS: Women exposed to the Famine, particularly those exposed after first
      birth, were more likely to be diagnosed with ER-PR-, ER-PR+, and ER+PR- breast
      cancer. This retrospective analysis suggests that famine, malnutrition, or the
      associated lack of fruit and vegetable consumption in adulthood may be related to
      epidemiological heterogeneity within breast cancer subtypes.

PMID- 27696083
TI  - Impact of apoptotic circulating tumor cells (aCTC) in metastatic breast cancer.
AB  - PURPOSE: While intact circulating tumor cells (iCTC) have independent negative
      prognostic impact on patients with metastatic breast cancer (MBC), the prognostic
      relevance of apoptotic CTC (aCTC) has not been validated in larger patient
      cohorts. This study assessed aCTC and iCTC statuses at baseline (CTCBL) and CTC
      kinetics (CTCKIN) as changes from CTCBL to one completed treatment cycle for
      their utility in predicting response, progression-free survival (PFS), and
      overall survival (OS) in MBC. METHODS: Status of iCTC and aCTC was prospectively
      assessed in 442 patients using the CellSearchTM system. Different cutoffs were
      analyzed both for iCTC and aCTC (>=5, >=10, >=25 and >=50 CTC/7.5 ml). CTCKIN
      were characterized by >=25 % changes in CTC counts. RESULTS: Numbers of iCTC and
      aCTC at baseline correlated strongly (r = 0.7). For iCTCBL positive patients,
      additional detection of aCTCBL had a significant prognostic impact on OS (aCTCBL
      positive 10.3 vs. aCTCBL negative 16.4 months, p = 0.012). Worst prognosis for OS
      was observed in patients with >=50 iCTC/7.5 ml and simultaneously detected aCTC.
      Determination of aCTCKIN showed stronger discriminating power than iCTCKIN, with
      higher PFS and OS for the group with decreasing CTCs (PFS 7.7 vs. 6.1; OS 22.2
      vs. 16.4). CONCLUSIONS: Intact and aCTC are predictive of outcome in MBC.
      Apoptotic CTC counts >= 5/7.5 ml in conjunction with iCTC at baseline have an
      independent unfavorable prognostic impact on OS. Decreasing aCTCKIN at >= 5/7.5
      ml in serial enumeration is associated with favorable outcome. Therefore,
      separate enumeration of iCTC and aCTC is useful in tailoring systemic treatment.

PMID- 27696084
TI  - Safe and effective use of rivaroxaban for treatment of cancer-associated venous
      thromboembolic disease: a prospective cohort study.
AB  - Low-molecular weight heparin (LMWH) has been the standard of care for treatment
      of venous thromboembolism (VTE) in patients with cancer. Rivaroxaban was approved
      in 2012 for the treatment of pulmonary embolism (PE) and deep vein thrombosis
      (DVT), but no prior studies have been reported specifically evaluating the
      efficacy and safety of rivaroxaban for cancer-associated thrombosis (CAT). Under
      a Quality Assessment Initiative (QAI), we established a Clinical Pathway to guide
      rivaroxaban use for CAT and now report a validation analysis of our first 200
      patients. A 200 patient cohort with CAT (PE or symptomatic, proximal DVT), whose
      full course of anticoagulation was with rivaroxaban, were accrued. In competing
      risk analysis, primary endpoints at 6 months included new or recurrent PE or
      symptomatic proximal lower extremity DVT, major bleeding, clinically-relevant non
      major bleeding leading to discontinuation of rivaroxaban, or death. In competing
      risk analysis, the 6 months cumulative incidence of new or recurrent VTE was 4.4
      % (95 % CI = 1.4-7.4 %), major bleeding was 2.2 % (95 % CI = 0-4.2 %) and all
      cause mortality 17.6 % (95 % CI = 11.7-23.0 %). In this cohort of 200 patients
      with active cancer and CAT the rates of new or recurrent VTE and major bleeding
      were comparable to the cancer subgroup analysis from the EINSTEIN studies. The
      results of our Clinical Pathway provide guidance on Rivaroxaban use for treatment
      of CAT, and suggest that safety and efficacy is preserved, compared with past
      published experience with LMWH.

PMID- 27696087
TI  - Risk factors for suture requirement and early hypotony in 23-gauge vitrectomy for
      complex vitreoretinal diseases.
AB  - PURPOSE: To find out the rate of suture requirement and post-operative hypotony
      in a series of 23-gauge pars plana vitrectomy cases and analyze the factors
      affecting post-operative hypotony and leakage of sclerotomy leading to suture
      placement. METHODS: This is a single-center retrospective interventional case
      series. Eighty-four eyes underwent 23-gauge vitrectomy. Primary endpoint measures
      were rate of leakage of 23-gauge sclerotomies requiring suture placement at the
      end of surgery and rate of early post-operative hypotony. Secondary endpoint
      measures were risk factors for early hypotony and leakage requiring suture
      placement at the end of surgery. RESULTS: Suture placement in at least one
      sclerotomy because of sclerotomy leakage was required in 28.6 % (24 of 84) of
      eyes at the end of surgery. Early post-operative hypotony was seen in 14.3 % (12
      of 84). Silicone oil endotamponade and single-step surgery were found as factors
      increasing the risk of sclerotomy leakage leading to suture placement. Suture
      placement was the only significant factor increasing the risk of early post
      operative hypotony. CONCLUSION: Sclerotomy sutures may be required in 23-gauge
      surgery, more frequently in cases of single-step sclerotomy and/or silicone oil
      endotamponade. Meticulous suturation of leaking sclerotomies may decrease the
      rate of post-operative hypotony.

PMID- 27696086
TI  - Adenosine A2A receptor regulates expression of vascular endothelial growth factor
      in feto-placental endothelium from normal and late-onset pre-eclamptic
      pregnancies.
AB  - We aim to investigate whether A2A/nitric oxide-mediated regulation of vascular
      endothelial growth factor (VEGF) expression is impaired in feto-placental
      endothelial cells from late-onset pre-eclampsia. Cultures of human umbilical vein
      endothelial cells (HUVECs) and human placental microvascular endothelial cells
      (hPMECs) from normal and pre-eclamptic pregnancies were used. Assays by using
      small interference RNA (siRNA) for A2A were performed, and transfected cells were
      used for estimation of messenger RNA (mRNA) levels of VEGF, as well as for cell
      proliferation and angiogenesis in vitro. CGS-21680 (A2A agonist, 24 h) increases
      HUVEC and hPMEC proliferation in a dose response manner. Furthermore, similar to
      CGS-21680, the nitric oxide donor, S-nitroso-N-acetyl-penicillamine oxide (SNAP),
      increased cell proliferation in a dose response manner (logEC50 10-9.2 M). In
      hPMEC, CGS-21680 increased VEGF protein levels in both normal (~1.5-fold) and pre
      eclamptic pregnancies (~1.2-fold), an effect blocked by the A2A antagonist, ZM
      241385 (10-5 M) and the inhibitor of NO synthase, N omega-nitro-L-arginine methyl
      ester hydrochloride (L-NAME). Subsequently, SNAP partially recovered cell
      proliferation and in vitro angiogenesis capacity of cells from normal pregnancies
      exposed to siRNA for A2A. CGS-21680 also increased (~1.5-fold) the level of VEGF
      mRNA in HUVEC from normal pregnancies, but not in pre-eclampsia. Additionally,
      transfection with siRNA for A2A decrease (~30 %) the level of mRNA for VEGF in
      normal pregnancy compared to untransfected cells, an effect partially reversed by
      co-incubation with SNAP. The A2A-NO-VEGF pathway is present in endothelium from
      microcirculation and macrocirculation in both normal and pre-eclamptic
      pregnancies. However, NO signaling pathway seems to be impaired in HUVEC from pre
      eclampsia.

PMID- 27696085
TI  - Transcriptomic effects of adenosine 2A receptor deletion in healthy and
      endotoxemic murine myocardium.
AB  - Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome
      and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic
      profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed
      by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac
      function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO
      (>=1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk
      and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2. Few
      canonical paths were impacted, with altered Gnb1, Prkar2b, Pde3b and Map3k2
      (among others) implicating modified G protein/cAMP/PKA and cGMP/NOS signalling.
      Lipopolysaccharide (LPS; 20 mg/kg) challenge for 24 h modified >4100 transcripts
      in wild-type (WT) myocardium (>=1.5-fold change, FDR < 1 %); the most induced are
      Lcn2 (+590); Saa3 (+516); Serpina3n (+122); Cxcl9 (+101) and Cxcl1 (+89) and the
      most repressed are Car3 (-38); Adipoq (-17); Atgrl1/Aplnr (-14); H19 (-11) and
      Itga8 (-8). Canonical responses centred on inflammation, immunity, cell death and
      remodelling, with pronounced amplification of toll-like receptor (TLR) and
      underlying JAK-STAT, NFkappaB and MAPK pathways, and a 'cardio-depressant'
      profile encompassing suppressed beta-adrenergic, PKA and Ca2+ signalling,
      electromechanical and mitochondrial function (and major shifts in transcripts
      impacting function/injury including Lcn2, S100a8/S100a9, Icam1/Vcam and Nox2
      induction, and Adipoq, Igf1 and Aplnr repression). Endotoxemic responses were
      selectively modified by A2AR KO, supporting inflammatory suppression via A2AR
      sensitive shifts in regulators of NFkappaB and JAK-STAT signalling (IkappaBzeta,
      IkappaBalpha, STAT1, CDKN1a and RRAS2) without impacting the cardio-depressant
      gene profile. Data indicate A2ARs exert minor effects in un-stressed myocardium
      and selectively suppress NFkappaB and JAK-STAT signalling and cardiac injury
      without influencing cardiac depression in endotoxemia.

PMID- 27696088
TI  - Differential evolution for protein folding optimization based on a three
      dimensional AB off-lattice model.
AB  - This paper presents a differential evolution algorithm that is adapted for the
      protein folding optimization on a three-dimensional AB off-lattice model. The
      proposed algorithm is based on a self-adaptive differential evolution that
      improves the algorithm efficiency and reduces the number of control parameters. A
      mutation strategy for the fast convergence is used inside the algorithm. A
      temporal locality is used in order to speed up the algorithm convergence
      additionally and to find amino-acid conformations with the lowest free energy
      values. Within this mechanism a new vector is calculated when the trial vector is
      better than the corresponding vector from the population. This new vector is
      likely better than the trial vector and this accelerates convergence speed.
      Because of the fast convergence the algorithm has some chance to be trapped into
      the local optima. To mitigate this problem the algorithm includes
      reinitialization. The proposed algorithm was tested on amino-acid sequences that
      are used frequently in literature. The obtained results show that the proposed
      algorithm is superior to the algorithms from the literature and the obtained
      amino-acid sequences have significantly lower free energy values. Graphical
      Abstract Protein folding optimization on a three-dimensional AB off-lattice model
      using the differential evolution algorithm.

PMID- 27696091
TI  - Hands Make Us Human.

PMID- 27696092
TI  - Levels of selected trace elements in Scots pine (Pinus sylvestris L.), silver
      birch (Betula pendula L.), and Norway maple (Acer platanoides L.) in an urbanized
      environment.
AB  - The aim of the study was to determine the concentrations of selected trace
      elements in needles and bark of Scots pine (Pinus sylvestris L.), leaves and bark
      of silver birch (Betula pendula L.), and Norway maple (Acer platanoides L.), as
      well as in the soil in which the trees grew, depending on their localization and
      hence the distribution of local pollution sources. The content of trace elements
      in needles of Scots pine, leaves of silver birch, and Norway maple and in bark of
      these trees depended on the location, tree species, and analyzed organ. The
      content of Fe, Mn, and Zn in needles, leaves, and bark of the examined tree
      species was significantly higher than that of the other elements. The highest
      average content of Fe and Mn was detected in leaves of Norway maple whereas the
      highest average content of Zn was found in silver birch leaves. The impact of
      such locations as the center of Olsztyn or roadside along Road 51 on the content
      of individual elements tended to be more pronounced than the influence of the
      other locations. The influence of the sampling sites on the content of trace
      elements in tree bark was less regular than the analogous effect in needles and
      leaves. Moreover, the relevant dependences were slightly different for Scots pine
      than for the other two tree species. The concentrations of heavy metals
      determined in the soil samples did not exceed the threshold values set in the
      Regulation of the Minister for the Environment, although the soil along Road 51
      and in the center of Olsztyn typically had the highest content of these elements.
      There were also significant correlations between the content of some trace
      elements in soil and their accumulation in needles, leaves, and bark of trees.

PMID- 27696093
TI  - Carcinogenic and endocrine-disrupting PAHs in the aquatic ecosystem of India.
AB  - The quantification studies of 17 carcinogenic and endocrine-disrupting polycyclic
      aromatic hydrocarbons (PAHs) in the Mithi River polluting the Mahim Creek near
      Mumbai were performed to understand their sources and probable ecological risk.
      The overall concentration level of SigmaPAHs was 157.96 +/- 18.99 MUg L-1, while
      that of carcinogenic PAHs (SigmaC-PAHs) was 81.31 +/- 9.75 MUg L-1, which
      corresponds to 51.5 % of the SigmaPAHs. The source analysis of PAH pollution was
      made on the basis of different PAH ratios. It was observed that the probable PAH
      contamination was due to pyrogenic inputs arising due to the combustion of grass,
      wood, and coal as well as due to the combustion of diesel and gasoline. Toxicity
      and biological risk assessment was made using toxic equivalent quantity (TEQ) for
      various C-PAHs. The results of our study showed that the mean BaP concentration
      in the Mithi River water (8.61 MUg L-1) was above the European Directive
      2008/105/EC Environmental Quality Standards (EQS) value of 0.05 MUg L-1, while
      the levels of benzo(k)fluoranthene (BkF) + benzo(b)fluoranthene (BbF) (21.54 MUg
      L-1) and benzo(g,h,i)perylene (BghiP) + indeno(1,2,3,-c,d) pyrene (InP) (18.27
      MUg L-1) were significantly higher than that set by the EQS (0.03 and 0.002 MUg L
      1, respectively), showing that the ecological integrity of the river and the
      adjoining creek is possibly at risk.

PMID- 27696096
TI  - Welcome Associate Editors Ajay Goel, Aida Habtezion, and Walter Park.

PMID- 27696094
TI  - A Macrophage Migration Inhibitory Factor Polymorphism Is Associated with
      Autoimmune Hepatitis Severity in US and Japanese Patients.
AB  - BACKGROUND: The pathogenesis of autoimmune hepatitis (AIH) is incompletely
      understood. Macrophage migration inhibitory factor (MIF) is an inflammatory
      cytokine implicated in the pathophysiology of multiple autoimmune diseases. We
      recently reported that MIF expression was increased in a US AIH cohort. MIF
      expression in non-Western AIH patients is unknown. A MIF-173 GC single nucleotide
      polymorphism in the MIF promoter (rs755622) is clinically associated with steroid
      resistance in several inflammatory disorders but has not been evaluated in AIH.
      AIM: To compare MIF polymorphisms and their relationship to clinical parameters
      in AIH patients from the USA and Japan. METHODS: DNA and matched sera from AIH
      patients and healthy controls from Japan (N = 52) were compared to the US group.
      Serum concentrations of MIF and its circulating receptor CD74 were measured by
      ELISA. MIF-173 GC (rs755622) and MIF-794 CATT5-8 (rs5844572) polymorphisms were
      analyzed by standard methods. MIF genotypes were correlated with serum ALT and
      steroid requirements. RESULTS: Serum MIF was increased in Japanese AIH patients
      versus local controls, in agreement with the US AIH patients. Within both AIH
      groups, ALT was higher in CC/GC versus GG patients. Further, the steroid
      requirement was higher in AIH patients with GC/CC genotypes from both groups. In
      the Japanese patient group, the GC/CC genotype also was associated with acute
      symptomatic presentation. CONCLUSIONS: The MIF-173 CC/GC genotypes may be
      associated with both higher ALT and maintenance steroid requirements in AIH
      patients from the USA and Japan. This polymorphism could be a marker of disease
      severity in AIH patients.

PMID- 27696095
TI  - Endoscopic Management of Large (>=2 cm) Non-pedunculated Colorectal Polyps:
      Impact of Polyp Morphology on Outcomes.
AB  - BACKGROUND AND AIMS: Referrals for endoscopic management of large non
      pedunculated (NP) colorectal polyps have increased as new techniques have
      emerged. The outcomes for referred large NP polyps based on the polyp morphology
      were investigated METHODS: A retrospective review of patients referred for large
      (>=20 mm) NP polyp management from January 2010 through June 2014 was completed.
      Polyp morphology was classified as either a NP polyp with depression (M1) or NP
      polyp with no depression (M0). Differences in treatment, histology, adverse
      events, outcomes at follow-up including residual disease, and need for surgical
      treatment were determined by morphology for all NP polyps >=20 mm in size.
      RESULTS: One-hundred and sixty-nine M1 and 136 M0 polyps >=20 mm were removed
      endoscopically during the review period. Mean size was 31.9 +/- 11.0 mm in M1,
      and 26.8 +/- 9.5 mm in M0 group (p < 0.0001). En bloc resection was possible in
      18.3 % of M1 and 30.9 % of M0 lesions (p = 0.011) with endoscopic submucosal
      dissection used in 13 and 2.2 % of polyps, respectively (p < 0.0001). Residual
      polyp was found in 26.5 % (27/102) of M1 and 13.6 % (12/88) of M0 patients at
      surveillance colonoscopy (p = 0.029). On multivariate analysis, piecemeal
      resection and M1 morphology showed significant association with residual polyp
      (OR 4.23, 95 % CI 1.23-14.59, p = 0.022, and OR 2.15, 95 % CI 1.004-4.62, p =
      0.049, respectively). CONCLUSION: Effective endoscopic management of large NP
      colorectal polyps, especially polyps without depression (M0), can be accomplished
      in the great majority of patients. Polyp morphology, particularly the presence or
      absence of depression, is a useful tool which influenced treatment, histology,
      and outcomes.

PMID- 27696097
TI  - The Child-Turcotte Classification: From Gestalt to Sophisticated Statistics and
      Back.

PMID- 27696098
TI  - Predictive Factors for Pain After Endoscopic Resection of Gastric Tumors.
AB  - BACKGROUND: Abdominal pain is a common complaint following endoscopic resection
      (ER). AIMS: To investigate the predictive factors for abdominal pain after ER.
      METHODS: Patients who were scheduled to undergo endoscopic mucosal resection or
      endoscopic submucosal dissection for the treatment of gastric adenoma or cancer
      were prospectively enrolled. Pain scores were checked every 6 h after ER and
      whenever patients complained of pain by using a 0-10 pain scale. If the pain
      score exceeded 5, 25 mg of intravenous (IV) pethidine was administered. RESULTS:
      Among 156 patients who underwent ER, 66 (42.3 %) received IV pethidine due to
      moderate/severe abdominal pain. Both the number of patients complaining of
      abdominal pain and the pain scores decreased with time following the procedure,
      with only a few patients complaining of mild abdominal pain 2 days after ER.
      Multivariate analysis showed that female sex [odds ratio (OR) 2.88; confidence
      interval (CI) 1.31-6.33], tumor location in the lower third of the stomach (OR
      5.46; CI 2.31-12.92), and procedures time more than 60 min (OR 2.96; CI 1.26
      6.98) were significant predictive factors for developing pain after ER.
      CONCLUSIONS: Female sex, tumor location in the lower third of the stomach, and
      longer procedure time were significantly associated with pain after ER. Close
      monitoring and active management of pain is recommended for patients who have
      these risk factors. With these efforts, the majority of patients could experience
      pain relief within 2 days after the procedure.

PMID- 27696099
TI  - Utilization of osteoporosis medication after a fragility fracture among elderly
      Medicare beneficiaries.
AB  - : Osteoporosis medications are recommended for elderly patients after a fragility
      fracture. However, we found substantial under-treatment in the post-fracture
      year, especially among patients who had not previously received such medications.
      Improved treatment of elderly patients experiencing fragility fractures is
      needed. INTRODUCTION: Osteoporosis medications are recommended for elderly
      patients after a fragility fracture, but under-treatment is common. We determined
      osteoporosis medication use after fragility fractures and examined associated
      factors. METHODS: Our cohort included elderly (age >=66 years) Medicare-enrolled
      patients who sustained fragility fractures January 1, 2008-December 31, 2011.
      Osteoporosis medication prescriptions were determined in the 12 months after the
      index fracture. Using multivariate logistic models, we examined the association
      between post-fracture osteoporosis medication use and predictors. RESULTS: Of
      145,185 patients with fragility fractures (mean age 80.9 +/- 7.8 years; 91.2 %
      white; 81.3 % female), 29.9 % sustained hip, 31.8 % vertebral, and 38.4 % non-hip
      non-vertebral fractures. Overall, 30.4 % of the cohort received an osteoporosis
      medication in the 12-month post-fracture period. Of patients not receiving an
      osteoporosis medication in the pre-index period (n = 108,344), 14.9 % of all
      patients, 16.3 % of women, and 10.3 % of men received one in the post-fracture
      period. Corresponding values for patients receiving an osteoporosis medication in
      the pre-index period (n = 36,841) were 76.2, 76.5, and 72.2 %. Odds of post
      fracture osteoporosis medication use were 68 % higher for women than for men.
      Osteoporosis diagnosis (odds ratio, 1.55; P < 0.0001) and bone-mineral-density
      tests before an index fracture (odds ratio, 1.24; P < 0.001) were associated with
      post-fracture osteoporosis medication use. CONCLUSIONS: Less than one third of
      our cohort received an osteoporosis medication in the post-fracture year, when
      risk of a second fragility fracture is highest. In those not already previously
      treated with an osteoporosis medication, only about 1 in 7 patients received
      treatment.

PMID- 27696100
TI  - Midterm Clinical Outcomes of Antrum Resection Margin at Laparoscopic Sleeve
      Gastrectomy for Morbid Obesity.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is one of the most frequently
      performed procedures in obesity surgery. The benefits of minimally invasive
      surgery include rapid recovery. We evaluated the clinical outcomes of different
      resection margin lengths from the pylorus in LSG. METHODS: This retrospective
      study included 152 patients who underwent LSG from January 2011 to October 2014.
      The antrum was resected 2 cm from the pylorus in 84 patients (group A) and 6 cm
      from the pylorus in 68 patients (group B). The patients' demographics, staple
      line distance, complications, sex, age, body mass index loss, length of hospital
      stay, and comorbidities were retrospectively reviewed. RESULTS: The patients
      comprised 104 women (68.4 %) and 48 men (32.6 %) with a mean age of 41.2 years
      (range, 28-53 years). The percent total and excess weight loss were statistically
      significant in both groups at 6 and 12 months postoperatively. Weight loss was
      significantly greater in group A than that in B at 6 and 12 months, but the
      difference at 24 months was not statistically significant. The results of pH
      monitoring showed significantly lower scores in group A than those in B at 6 and
      12 months, but no difference at 24 months. CONCLUSION: LSG is an effective
      procedure with good short-term outcomes. Both procedures described herein are
      equally effective with respect to the patient's return to daily activities.
      Increasing the distance from the resection line to the pylorus is associated with
      better weight loss but slightly increased symptoms of gastroesophageal reflux
      disease without a significant difference in complications.

PMID- 27696101
TI  - Non-musicians also have a piano in the head: evidence for spatial-musical
      associations from line bisection tracking.
AB  - The spatial representation of ordinal sequences (numbers, time, tones) seems to
      be a fundamental cognitive property. While an automatic association between
      horizontal space and pitch height (left-low pitch, right-high pitch) is
      constantly reported in musicians, the evidence for such an association in non
      musicians is mixed. In this study, 20 non-musicians performed a line bisection
      task while listening to irrelevant high- and low-pitched tones and white noise
      (control condition). While pitch height had no influence on the final bisection
      point, participants' movement trajectories showed systematic biases: When
      approaching the line and touching the line for the first time (initial bisection
      point), the mouse cursor was directed more rightward for high-pitched tones
      compared to low-pitched tones and noise. These results show that non-musicians
      also have a subtle but nevertheless automatic association between pitch height
      and the horizontal space. This suggests that spatial-musical associations do not
      necessarily depend on constant sensorimotor experiences (as it is the case for
      musicians) but rather reflect the seemingly inescapable tendency to represent
      ordinal information on a horizontal line.

PMID- 27696102
TI  - Clinician behaviors in telehealth care delivery: a systematic review.
AB  - Literature on telehealth care delivery often addresses clinical, cost,
      technological, system, and organizational impacts. Less is known about
      interpersonal behaviors such as communication patterns and therapeutic
      relationship-building, which may have workforce development considerations. The
      purpose of this study was to conduct a systematic literature review to identify
      interpersonal health care provider (HCP) behaviors and attributes related to
      provider-patient interaction during care in telehealth delivery. Electronic
      searches were conducted using five indexes/databases: CINAHL, ERIC, PsychInfo,
      ProQuest Dissertations, PubMed; with hand-searching of the immediate past 10
      years of five journals. Search concepts included: communication, telehealth,
      education, and health care delivery. Of 5261 unique article abstracts initially
      identified, 338 full-text articles remained after exclusion criteria were applied
      and these were reviewed for eligibility. Finally, data were extracted from 45
      articles. Through qualitative synthesis of the 45 articles, we noted that papers
      encompassed many disciplines and targeted care to people in many settings
      including: home care, primary and specialist care, mental health/counseling, and
      multi-site teams. Interpersonal behaviors were observed though not manipulated
      through study designs. Six themes were identified: HCP-based support for
      telehealth delivery; provider-patient interactions during the telehealth event;
      environmental attributes; and guidelines for education interventions or
      evaluation of HCP behaviors. Although unable to identify current best practices,
      important considerations for practice and education did emerge. These include:
      perceptions of the utility of telehealth; differences in communication patterns
      such as pace and type of discourse, reliance on visual cues by both provider and
      patient especially in communicating empathy and building rapport; and
      confidentiality and privacy in telehealth care delivery.

PMID- 27696103
TI  - Validity: one word with a plurality of meanings.
AB  - Validity is one of the most debated constructs in our field; debates abound about
      what is legitimate and what is not, and the word continues to be used in ways
      that are explicitly disavowed by current practice guidelines. The resultant
      tensions have not been well characterized, yet their existence suggests that
      different uses may maintain some value for the user that needs to be better
      understood. We conducted an empirical form of Discourse Analysis to document the
      multiple ways in which validity is described, understood, and used in the health
      professions education field. We created and analyzed an archive of texts
      identified from multiple sources, including formal databases such as PubMED, ERIC
      and PsycINFO as well as the authors' personal assessment libraries. An iterative
      analytic process was used to identify, discuss, and characterize emerging
      discourses about validity. Three discourses of validity were identified. Validity
      as a test characteristic is underpinned by the notion that validity is an
      intrinsic property of a tool and could, therefore, be seen as content and context
      independent. Validity as an argument-based evidentiary-chain emphasizes the
      importance of supporting the interpretation of assessment results with ongoing
      analysis such that validity does not belong to the tool/instrument itself. The
      emphasis is on process-based validation (emphasizing the journey instead of the
      goal). Validity as a social imperative foregrounds the consequences of assessment
      at the individual and societal levels, be they positive or negative. The
      existence of different discourses may explain-in part-results observed in recent
      systematic reviews that highlighted discrepancies and tensions between
      recommendations for practice and the validation practices that are actually
      adopted and reported. Some of these practices, despite contravening accepted
      validation 'guidelines', may nevertheless respond to different and somewhat
      unarticulated needs within health professional education.

PMID- 27696104
TI  - How well does the reproductive tract manage infectious agents?

PMID- 27696105
TI  - Blastomere biopsy for PGD delays embryo compaction and blastulation: a time-lapse
      microscopic analysis.
AB  - PURPOSE: The purpose of the study was to explore the effect of blastomere biopsy
      for preimplantation genetic diagnosis (PGD) on the embryos' dynamics, further
      cleavage, development, and implantation. METHODS: The study group included 366
      embryos from all PGD treatments (September 2012 to June 2014) cultured in the
      EmbryoScopeTM time-lapse monitoring system. The control group included all
      intracytoplasmic sperm injection (ICSI) embryos cultured in EmbryoScopeTM until
      day 5 during the same time period (385 embryos). Time points of key embryonic
      events were analyzed with an EmbryoViewerTM. RESULTS: Most (88 %) of the embryos
      were biopsied at >=8 cells. These results summarize the further dynamic
      development of the largest cohort of biopsied embryos and demonstrate that
      blastomere biopsy of cleavage-stage embryos significantly delayed compaction and
      blastulation compared to the control non-biopsied embryos. This delay in
      preimplanation developmental events also affected postimplantation development as
      observed when the dynamics of non-implanted embryos (known implantation data
      (KID) negative) were compared to those of implanted embryos (KID positive).
      CONCLUSION: Analysis of morphokinetic parameters enabled us to explore how
      blastomere biopsy interferes with the dynamic sequence of developmental events.
      Our results show that biopsy delays the compaction and the blastulation of the
      embryos, leading to a decrease in implantation.

PMID- 27696106
TI  - In vitro and in vivo antitumor effects of the VO-chrysin complex on a new three
      dimensional osteosarcoma spheroids model and a xenograft tumor in mice.
AB  - Osteosarcoma (OS) is the most common primary tumor of bone, occurring
      predominantly in the second decade of life. High-dose cytotoxic chemotherapy and
      surgical resection have improved prognosis, with long-term survival for patients
      with localized disease. Vanadium is an ultra-trace element that after being
      absorbed accumulates in bone. Besides, vanadium compounds have been studied
      during recent years to be considered as representative of a new class of non
      platinum antitumor agents. Moreover, flavonoids are a wide family of polyphenolic
      compounds that display many interesting biological effects. Since coordination of
      ligands to metals can improve the pharmacological properties, we report herein,
      for the first time, the in vitro and in vivo effects of an oxidovanadium(IV)
      complex with the flavonoid chrysin on the new 3D human osteosarcoma and xenograft
      osteosarcoma mice models. The pharmacological results show that VOchrys inhibited
      the cell viability affecting the shape and volume of the spheroids and VOchrys
      suppressed MG-63 tumor growth in the nude mice without inducing toxicity and side
      effects. As a whole, the results presented herein demonstrate that the antitumor
      action of the complex was very promissory on human osteosarcoma models, whereby
      suggesting that VOchrys is a potentially good candidate for future use in
      alternative antitumor treatments.

PMID- 27696108
TI  - Higher Serum Uric Acid May Contribute to Cerebral Infarction in Patients with
      Type 2 Diabetes Mellitus: a Meta-Analysis.
AB  - Higher levels of serum uric acid tend to increase the diabetes-related
      complications. We performed a meta-analysis to investigate whether the higher
      serum uric acid levels were associated with cerebral infarction in type 2
      diabetes patients. We searched for relevant studies in the PubMed, Embase, China
      National Knowledge Infrastructure, China BioMedicine, and VIP database until
      August 2015. All observational studies comparing serum uric acid levels in type 2
      diabetic patients with and without cerebral infarction were included. We
      calculated the ratio of means (RoM) of serum uric acid by mean cerebral
      infarction/mean diabetic control from the individual studies and then pooled RoM
      and its 95 % confidence intervals (CI). A total of 23 eligible studies were
      identified. Pooled estimates indicated that type 2 diabetes patients with
      cerebral infarction were associated with 29 % (RoM 1.29; 95 % CI 1.26-1.31)
      higher serum uric acid levels than those without cerebral infarction in a random
      effect model. Subgroup analyses based on gender indicated that RoM was 1.23 (95 %
      CI 1.09-1.38) for men and 1.12 (95 % CI 0.98-1.27) for women. This meta-analysis
      suggests that higher serum uric acid levels may contribute to cerebral infarction
      in patients with type 2 diabetes.

PMID- 27696109
TI  - Effects of horticulture therapy on nursing home older adults in southern Taiwan.
AB  - PURPOSE: This study aimed to test the effects of horticulture therapy on
      activities of daily living, happiness, meaning of life, and interpersonal
      intimacy of nursing home older adults in southern Taiwan. METHODS: A quasi
      experimental study was applied. Eighty-five older adults aged 65 or older who
      lived in nursing homes in southern Taiwan were recruited conveniently. All
      participants completed the study: experimental group (n = 41) and control group
      (n = 44). The experimental group received horticulture therapy for 1 h once a
      week for 8 weeks, while the control group continued their routine daily
      activities. The following questionnaires were administered before and after the
      intervention period: (1) Barthel Index (BI), (2) Chinese Happiness Inventory
      short version (CHI), (3) Meaning of Life Scale (MLS), and (4) Interpersonal
      Intimacy Scale (IIS). RESULTS: The BI, CHI, MLS, and IIS scores significantly
      improved in the experimental group (p < .05). After 8 weeks of horticulture
      therapy, the BI, CHI, and IIS scores of experimental group participants were
      significantly better than the scores of control group participants (p < .05);
      however, the MLS scores of two groups showed no significant differences (p =
      .738). CONCLUSIONS: Horticulture therapy improved activities of daily living,
      happiness, and interpersonal intimacy of older adults in nursing homes. We
      recommend that nursing homes recruit and train personnel to lead horticultural
      therapy and to incorporate the therapy as routine daily activities in the
      facilities.

PMID- 27696107
TI  - Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene
      panel testing.
AB  - Hereditary syndromes causing colorectal cancer include both polyposis and non
      polyposis syndromes. Overlapping phenotypes between the syndromes have been
      recognized and this make targeted molecular testing for single genes less
      favorable, instead there is a gaining interest for multi-gene panel-based
      approaches detecting both SNVs, indels and CNVs in the same assay. We applied a
      panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic
      subgroups. Targeted NGS-based sequencing of the whole gene regions including
      introns of the 19 genes was used. The individuals had a family history of CRC or
      had a phenotype consistent with a known CRC syndrome. The purpose of the study
      was to demonstrate the diagnostic difficulties linked to genotype-phenotype
      diversity and the benefits of using a gene panel. Pathogenicity classification
      was carried out on 46 detected variants. In total we detected sixteen pathogenic
      or likely pathogenic variants and 30 variants of unknown clinical significance.
      Four of the pathogenic or likely pathogenic variants were found in BMPR1A in
      patients with unexplained familial adenomatous polyposis or atypical adenomatous
      polyposis, which extends the genotype-phenotype spectrum for this gene. Nine
      patients had more than one variant remaining after the filtration, including
      three with truncating mutations in BMPR1A, PMS2 and AXIN2. CNVs were found in
      three patients, in upstream regions of SMAD4, MSH3 and CTNNB1, and one additional
      individual harbored a 24.2 kb duplication in CDH1 intron1.

PMID- 27696110
TI  - Change in physical function among women as they age: findings from the Australian
      Longitudinal Study on Women's Health.
AB  - PURPOSE: Decline in physical function is common in older age, with important
      consequences for health-related quality of life, health care utilisation, and
      mortality. This study aimed to identify patterns of change in physical
      functioning (PF) for women in later life. METHODS: PF was measured longitudinally
      using the ten-item subscale of the Medical Outcomes Study 36-item Short Form
      Health Survey, for 10 515 participants of the Australian Longitudinal Study on
      Women's Health, who completed at least two surveys between 1999 (aged 73-78
      years) and 2011 (aged 85-90 years). Conditional and unconditional latent profile
      analysis was conducted separately for deceased and surviving subgroups of women
      to uncover latent patterns of change in PF scores over time. RESULTS: Four
      patterns of change were identified for women who were still alive in 2011 (N =
      5928), and four similar classes for deceased women (N = 4587): (1) 'poor PF'
      representing women with low PF scores, (2) 'moderate PF', (3) 'high PF', and (4)
      'very high PF', where scores remained very high. All patterns exhibited a
      decrease in PF over time. Factors which predict low PF included sedentary levels
      of exercise, obese and overweight BMI, difficulty managing on income, and lower
      education. CONCLUSIONS: The results provided evidence for a gradual decrease in
      PF for all women with age; however, there was no evidence for an increased rate
      of decline prior to death.

PMID- 27696111
TI  - Atrial-focused views improve the accuracy of two-dimensional echocardiographic
      measurements of the left and right atrial volumes: a contribution to the increase
      in normal values in the guidelines update.
AB  - Current guidelines recommend that the atria be measured in 2D echocardiographic
      (2DE) apical views using the method-of-disks (MOD) or area-length (AL) technique
      as an alternative, although no definitive data exists that these are
      interchangeable. However, standard apical views maximize the long-axis of the
      left ventricle, rather than the dimensions of the atria, resulting in atrial
      foreshortening. We hypothesized that the increase in normal values of atrial
      volumes in the recent guidelines update was driven by data obtained using either
      the AL technique or dedicated atrial-focused views, which maximize the
      longitudinal dimension of the atria and thus provide larger volumes than the MOD
      measurements in standard apical views. We prospectively studied 30 patients
      (Philips iE33) to compare 2DE measurements of left and right atrial volumes (LAV,
      RAV) using the MOD and AL techniques in standard and atrial-focused views,
      against 3D echocardiography (3DE) derived volumes (QLab) as a reference. Compared
      to standard views, atrial-focused views provided significantly larger MOD volumes
      for both atria, which were in better agreement with 3DE, as reflected by higher
      correlation coefficients (LAV: r = 0.95 vs. 0.89; RAV: r = 0.89 vs. 0.84),
      smaller biases (LAV: -1 ml vs. 7 ml; RAV: 3 ml vs. 7 ml) and tighter limits of
      agreement. This was also the case for the AL measurements, which were minimally
      larger than the MOD values (NS) for both atria. In conclusion, atrial-focused
      views are a more accurate alternative to standard apical views, which provides
      larger volumes. This finding can explain the increase in the normal values in the
      recent guidelines update, which was mostly driven by the use of atrial-focused
      views, rather than by the differences between MOD and AL techniques. This
      understanding is essential in order to correctly integrate the revised normal
      values into clinical practice.

PMID- 27696113
TI  - The gating of the CFTR channel.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel
      expressed in the apical membrane of epithelia. Mutations in the CFTR gene are the
      cause of cystsic fibrosis. CFTR is the only ABC-protein that constitutes an ion
      channel pore forming subunit. CFTR gating is regulated in complex manner as
      phosphorylation is mandatory for channel activity and gating is directly
      regulated by binding of ATP to specific intracellular sites on the CFTR protein.
      This review covers our current understanding on the gating mechanism in CFTR and
      illustrates the relevance of alteration of these mechanisms in the onset of
      cystic fibrosis.

PMID- 27696112
TI  - Laminin: loss-of-function studies.
AB  - Laminin, one of the most widely expressed extracellular matrix proteins, exerts
      many important functions in multiple organs/systems and at various developmental
      stages. Although its critical roles in embryonic development have been
      demonstrated, laminin's functions at later stages remain largely unknown, mainly
      due to its intrinsic complexity and lack of research tools (most laminin mutants
      are embryonic lethal). With the advance of genetic and molecular techniques, many
      new laminin mutants have been generated recently. These new mutants usually have
      a longer lifespan and show previously unidentified phenotypes. Not only do these
      studies suggest novel functions of laminin, but also they provide invaluable
      animal models that allow investigation of laminin's functions at late stages.
      Here, I first briefly introduce the nomenclature, structure, and biochemistry of
      laminin in general. Next, all the loss-of-function mutants/models for each
      laminin chain are discussed and their phenotypes compared. I hope to provide a
      comprehensive review on laminin functions and its loss-of-function models, which
      could serve as a reference for future research in this understudied field.

PMID- 27696114
TI  - Pinocembrin Provides Mitochondrial Protection by the Activation of the Erk1/2
      Nrf2 Signaling Pathway in SH-SY5Y Neuroblastoma Cells Exposed to Paraquat.
AB  - Pinocembrin (PB; 5,7-dihydroxyflavanone; C15H12O4) is a flavonoid found in
      propolis and exerts antioxidant, anti-inflammatory, and antimicrobial effects.
      Furthermore, PB has been studied as a neuroprotective agent. However, it remains
      to be understood whether and how PB would induce mitochondrial protection in
      mammalian cells. Therefore, we investigated here the mechanism involved in the
      protective effects elicited by PB in paraquat (PQ; 100 MUM)-treated SH-SY5Y
      neuroblastoma cells. PB (25 MUM) pretreatment (for 4 h) downregulated the levels
      of Bcl-2-associated X protein (Bax), blocked the release of cytochrome c to the
      cytosol, and inhibited the PQ-induced activation of caspase-9 and caspase-3.
      Besides, PB prevented mitochondrial dysfunction by suppressing the PQ-elicited
      inhibition of complexes I and V. Moreover, PB abrogated the loss of mitochondrial
      membrane potential (MMP) and the decline in ATP levels in the cells exposed to
      PQ. PB exerted antioxidant effects on mitochondria by decreasing the levels of
      redox impairment markers in mitochondrial membranes. Importantly, PB enhanced the
      levels of mitochondrial reduced glutathione (GSH). Upregulation of enzymes
      involved in the synthesis of GSH was seen in the cells exposed to PB. PB afforded
      mitochondrial protection by activating the extracellular signal-regulated
      kinase/nuclear factor erythroid 2-related factor 2 (Erk1/2-Nrf2) axis, since
      inhibition of Erk1/2 or silencing of Nrf2 abrogated these effects. Therefore, PB
      exerted mitochondrial and cellular protection by an Erk1/2-Nrf2-dependent
      mechanism.

PMID- 27696115
TI  - The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is
      Mediated by Alox15 Activity in the Prefrontal Cortex.
AB  - Pain and anxiety have a complex relationship and pain is known to share
      neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory
      pathways of pain have been shown to originate from cortical and subcortical
      regions, including the dorsolateral prefrontal cortex. In this study, a novel
      docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered
      to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral
      responses recorded. Infraorbital nerve ligation resulted in increased face wash
      strokes of the face upon von Frey hair stimulation, indicating increased
      nociception. Part of this response involves general pain sensitization that is
      dependent on the CNS, since increased nociception was also found in the paws
      during the hot plate test. Mice receiving oral gavage of Souvenaid, a
      nutraceutical containing DHA; choline; and other cell membrane components, showed
      significantly reduced pain sensitization. The mechanism of Souvenaid's activity
      involves supraspinal antinociception, originating in the prefrontal cortex, since
      inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the
      prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15
      inhibition also modulated anxiety behavior associated with pain after
      infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on
      reducing central sensitization of pain may be due to strengthening of a known
      supraspinal antinociceptive pathway from the prefrontal cortex to the
      periaqueductal gray. Together, results indicate the importance of the prefrontal
      cortex and DHA/Alox15 in central antinociceptive pathways and suggest that
      Souvenaid may be a novel therapeutic for neuropathic pain.

PMID- 27696118
TI  - A Tribute to Steve White.

PMID- 27696117
TI  - Pathogenic variants in HTRA2 cause an early-onset mitochondrial syndrome
      associated with 3-methylglutaconic aciduria.
AB  - Mitochondrial diseases collectively represent one of the most heterogeneous group
      of metabolic disorders. Symptoms can manifest at any age, presenting with
      isolated or multiple-organ involvement. Advances in next-generation sequencing
      strategies have greatly enhanced the diagnosis of patients with mitochondrial
      disease, particularly where a mitochondrial aetiology is strongly suspected yet
      OXPHOS activities in biopsied tissue samples appear normal. We used whole exome
      sequencing (WES) to identify the molecular basis of an early-onset mitochondrial
      syndrome-pathogenic biallelic variants in the HTRA2 gene, encoding a mitochondria
      localised serine protease-in five subjects from two unrelated families
      characterised by seizures, neutropenia, hypotonia and cardio-respiratory
      problems. A unifying feature in all affected children was 3-methylglutaconic
      aciduria (3-MGA-uria), a common biochemical marker observed in some patients with
      mitochondrial dysfunction. Although functional studies of HTRA2 subjects'
      fibroblasts and skeletal muscle homogenates showed severely decreased levels of
      mutant HTRA2 protein, the structural subunits and complexes of the mitochondrial
      respiratory chain appeared normal. We did detect a profound defect in OPA1
      processing in HTRA2-deficient fibroblasts, suggesting a role for HTRA2 in the
      regulation of mitochondrial dynamics and OPA1 proteolysis. In addition,
      investigated subject fibroblasts were more susceptible to apoptotic insults. Our
      data support recent studies that described important functions for HTRA2 in
      programmed cell death and confirm that patients with genetically-unresolved 3-MGA
      uria should be screened by WES with pathogenic variants in the HTRA2 gene
      prioritised for further analysis.

PMID- 27696116
TI  - A Mitocentric View of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease with an increasing
      morbidity, mortality, and economic cost. Plaques formed by amyloid beta peptide
      (Abeta) and neurofibrillary tangles formed by microtubule-associated protein tau
      are two main characters of AD. Though previous studies have focused on Abeta and
      tau and got some progressions on their toxicity mechanisms, no significantly
      effective treatments targeting the Abeta and tau have been found. However, it is
      worth noting that mounting evidences showed that mitochondrial dysfunction is an
      early event during the process of AD pathologic changes. What is more, these
      studies also showed an obvious association between mitochondrial dysfunction and
      Abeta/tau toxicity. Furthermore, both genetic and environmental factors may
      increase the oxidative stress and the mitochondria are also the sensitive target
      of ROS, which may form a vicious feedback between mitochondrial dysfunction and
      oxidative stress, eventually resulting in deficient energy, synaptic failure, and
      cell death. This article reviews the previous related studies from different
      aspects and concludes the critical roles of mitochondrial dysfunction in AD,
      suggesting a different route to AD therapy, which may guide the research and
      treatment direction.

PMID- 27696119
TI  - Interactions in the Metabolism of Glutamate and the Branched-Chain Amino Acids
      and Ketoacids in the CNS.
AB  - Glutamatergic neurotransmission entails a tonic loss of glutamate from nerve
      endings into the synapse. Replacement of neuronal glutamate is essential in order
      to avoid depletion of the internal pool. In brain this occurs primarily via the
      glutamate-glutamine cycle, which invokes astrocytic synthesis of glutamine and
      hydrolysis of this amino acid via neuronal phosphate-dependent glutaminase. This
      cycle maintains constancy of internal pools, but it does not provide a mechanism
      for inevitable losses of glutamate N from brain. Import of glutamine or glutamate
      from blood does not occur to any appreciable extent. However, the branched-chain
      amino acids (BCAA) cross the blood-brain barrier swiftly. The brain possesses
      abundant branched-chain amino acid transaminase activity which replenishes brain
      glutamate and also generates branched-chain ketoacids. It seems probable that the
      branched-chain amino acids and ketoacids participate in a "glutamate-BCAA cycle"
      which involves shuttling of branched-chain amino acids and ketoacids between
      astrocytes and neurons. This mechanism not only supports the synthesis of
      glutamate, it also may constitute a mechanism by which high (and potentially
      toxic) concentrations of glutamate can be avoided by the re-amination of branched
      chain ketoacids.

PMID- 27696121
TI  - Pituitary abscess: clinical manifestations, diagnosis and treatment of 66 cases
      from a large pituitary center over 23 years.
AB  - PURPOSE: Pituitary abscess (PA) is rare and commonly described in case reports or
      small case series. This study aimed to better determine salient clinical
      manifestations related to the diagnosis and appropriate treatment of PA using by
      far the largest case series of this disease. METHODS: A total of 6361 consecutive
      patients underwent surgery for pituitary diseases in Peking Union Medical College
      Hospital between January 1991 and December 2013. Among this cohort, sixty-six
      patients were diagnosed with PA based on both intraoperative findings and
      postoperative histopathological evidence. RESULTS: The most common clinical
      presentation was anterior pituitary hypofunction (81.8 %), followed by common
      headache (69.7 %), diabetes insipidus (DI; 47.9 %), visual disturbances (45.5 %)
      and symptoms related to infection (43.9 %). Forty patients (66.7 %) showed
      typical rim enhancement after gadolinium injection on magnetic resonance imaging
      (MRI). Most patients (63 of 66, 95.5 %) underwent transsphenoidal surgery (TSS),
      and the remaining 3 patients (4.5 %) were treated with transcranial surgery (TC).
      After follow-up for 7.2 +/- 4.9 years, PA was diminished in most patients (81.8
      %), as demonstrated by post-operative MRI, and eight patients underwent at least
      one additional operation due to recurrence. CONCLUSIONS: For patients with
      hypopituitarism and DI with rim enhancement on MRI, we should consider the
      possible diagnosis of PA. Proper use of antibiotics, complete drainage via
      surgery and hormone replacement for hypopituitarism are the key treatments for
      PA.

PMID- 27696120
TI  - Role of Estradiol in the Regulation of Prolactin Secretion During Late Pregnancy.
AB  - Estrogen action is necessary for evidencing the stimulatory action of
      mifepristone and naloxone on prolactin (PRL) secretion during late pregnancy. Our
      aim is to determine the mechanism mediating this facilitator action of estrogens.
      To investigate the hypothalamic mechanisms involved in estrogen actions in PRL
      secretion at the end of pregnancy, we measured the effect of pretreatment with
      the estrogen antagonist tamoxifen on the expression of tyrosine hydroxylase (TH),
      hormone receptors (ERalpha and beta, PRs, PRLR(long)), and MU- and kappa- opioid
      receptors (ORs) at mRNA (by semiquantitative RT-PCR) and protein (by western blot
      for TH, PRLR(long), ERalpha, PRs, MU- and ORs) levels in extracts of medial basal
      hypothalamus (MBH) and serum PRL, E2 and P4 levels (by RIA) in mifepristone- and
      naloxone-treated rats. Tamoxifen administration partially prevented PRL release
      induced by the combined treatment. TH expression diminished and ERalpha
      expression increased in mifepristone-treated rats at mRNA and protein levels and
      tamoxifen partially prevented these changes with no effect on PRs expression.
      Mifepristone increased PRLR(long) mRNA levels; this increase was blocked by
      tamoxifen. Combined tamoxifen and mifepristone treatment decreased MU- and k-ORs
      mRNA but not protein levels. In conclusion, E2 induces neuroadaptive mechanisms
      necessary to facilitate PRL release preceding delivery. Acting through ERalpha,
      E2 modulates hypothalamic dopaminergic neurons activity, regulating TH, MU- and
      kappa-ORs and PRLR(long) expression, and is necessary for evidencing the effects
      of P4 withdrawal. Its presence on days 14 and 15 of pregnancy is crucial to
      facilitate the opioid system modulation of PRL secretion at the end of pregnancy
      in the rat.

PMID- 27696122
TI  - PD-1/PD-L1 expression in chromophobe renal cell carcinoma: An immunological
      exception?
AB  - Immune checkpoint inhibitors targeting the inhibitory cross talk between tumor
      and immune cells have been approved for therapy in renal cell carcinoma (RCC). In
      contrast to clear cell RCC, little is known on PD-1/PD-L1 expression patterns in
      rarer RCC subtypes. The aim of this study was to evaluate the prevalence,
      distribution and prognostic impact of PD-1 and PD-L1 expression in chromophobe
      (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively
      evaluated. Tumor specimen was analyzed for PD-1 and PD-L1 expression by
      immunohistochemistry. Expression data were correlated with clinic-pathological
      parameters including patient survival. Eighty-one chRCC patients were eligible
      for analysis, thereof 25 (30.9 %) and 11 (13.6 %) patients were positive for PD
      1+ tumor-infiltrating mononuclear cells (TIMCs) and tumoral PD-L1+ expression,
      respectively. No significant associations were found for PD-1+ TIMC or tumoral PD
      L1+ expression and clinical attributes. In addition, no differences in 5- and 10
      year overall survival for PD-1- TIMC compared to PD-1+ TIMC (90.5 and 72.2 vs.
      100 and 75 %; p = 0.41) and for PD-L1- tumors compared to PD-L1+ tumors (91.9 and
      76.4 vs. 100 and 50 %; p = 0.48) were observed. In conclusion, to our knowledge
      this is the first study to evaluate the prognostic impact of PD-1 and PD-L1 in
      chRCC. PD-L1 does seem to be expressed in a minority of all chRCC, likewise only
      a minority of chRCC was infiltrated by PD-1-positive inflammatory cells. Neither
      PD-1+ TIMC nor tumoral PD-L1+ expression was associated with parameters of
      aggressiveness or survival.

PMID- 27696123
TI  - Sexual Reproduction in Dermatophytes.
AB  - Sexual reproduction is a rich source of genetic variation and commonly observed
      among fungi. Basically two different modes of sexual reproduction are observed in
      fungi, namely heterothallism where two compatible mating types are required to
      undergo mating and homothallism in which the organism is self-fertile. The
      genomic region governing the process of sexual reproduction and sex determination
      is called the mating type (MAT) locus. In filamentous ascomycetes including
      dermatophytes, the MAT locus harbors two different transcription factor genes in
      two different mating types. This review focuses on sexual reproduction and the
      structure of the MAT locus in dermatophytes. The reproductive modes and the
      observed mating types are summarized for different phylogenetic clades of
      dermatophytes. In addition, the question of whether or not unisexual
      reproduction, an interesting form of homothallism, may be the sexual reproduction
      mode especially in anthropophilic dermatophytes is raised.

PMID- 27696125
TI  - Meniscal allograft subluxations are not associated with preoperative native
      meniscal subluxations.
AB  - PURPOSE: To determine the relationship between preoperative subluxation of the
      original menisci and postoperative graft subluxation after lateral meniscal
      allograft transplantation (MAT). METHODS: Forty patients who underwent isolated
      lateral MATs in meniscus-deficient knees with a low-grade chondral lesion (<=ICRS
      grade 2) were assessed. Lateral subluxation of the native meniscus before
      meniscectomy and those of remaining meniscal tissue before MAT were measured on
      mid-coronal MRI scans taken at each time point. Postoperative meniscal
      subluxation was assessed using MRI at 6 months postoperatively, when the full
      rehabilitation protocols were completed. Correlation analyses were conducted to
      determine the associations between each of two preoperative lateral displacements
      and the postoperative graft subluxation. RESULTS: The mean lateral subluxations
      before primary meniscectomy and before MAT were 0.3 +/- 1.0 mm and 0.2 +/- 0.8
      mm, respectively. At 6 months postoperatively, it was 2.3 +/- 1.9 mm. There were
      no significant correlations between the preoperative subluxation at the two
      preoperative time points and the postoperative extrusion (Spearman rho 2-sided
      test: rho = - 0.058, (n.s.) for the native meniscus; Pearson r 2-sided test, r =
      0.309, (n.s.) for the remaining meniscal rim). Between the postoperative
      nonextruded and extruded groups, there were no significant differences for the
      preoperative subluxations. CONCLUSIONS: There are no associations between
      preoperative lateral subluxation of the native menisci and postoperative
      subluxation of meniscal transplants in patients who undergo MAT on the lateral
      compartment with low-grade arthritic changes. The extrusion phenomenon may be a
      distinct feature of transplanted menisci rather than an individual characteristic
      of meniscal displacement. Surgeons need to keep in mind that graft extrusion in
      nonarthritic knees might occur during transplantation. LEVEL OF EVIDENCE: IV.

PMID- 27696126
TI  - Integration of behavioral health and primary care: current knowledge and future
      directions.
AB  - Integrated behavioral health in primary care has spread rapidly over the past
      three decades, although significant questions remain unanswered regarding best
      practices in clinical, financial and operational worlds. Two key models have
      emerged over time: care management and Primary Care Behavioral Health. Research
      to date has been promising; however, there is a significant need for more
      sophisticated multi-level scientific methodologies to fill in the gaps in current
      knowledge of integrated primary care. In this paper, we summarize current
      scientific knowledge about integrated primary care and critically evaluate the
      strengths and weaknesses of this knowledge base, focusing on clinical, financial
      and operational factors. Finally, we recommended priorities for future research,
      dissemination, real-world implementation, and health policy implications.

PMID- 27696124
TI  - Peripheral blood mononuclear cell secretome for tissue repair.
AB  - For almost two decades, cell-based therapies have been tested in modern
      regenerative medicine to either replace or regenerate human cells, tissues, or
      organs and restore normal function. Secreted paracrine factors are increasingly
      accepted to exert beneficial biological effects that promote tissue regeneration.
      These factors are called the cell secretome and include a variety of proteins,
      lipids, microRNAs, and extracellular vesicles, such as exosomes and
      microparticles. The stem cell secretome has most commonly been investigated in
      pre-clinical settings. However, a growing body of evidence indicates that other
      cell types, such as peripheral blood mononuclear cells (PBMCs), are capable of
      releasing significant amounts of biologically active paracrine factors that exert
      beneficial regenerative effects. The apoptotic PBMC secretome has been
      successfully used pre-clinically for the treatment of acute myocardial
      infarction, chronic heart failure, spinal cord injury, stroke, and wound healing.
      In this review we describe the benefits of choosing PBMCs instead of stem cells
      in regenerative medicine and characterize the factors released from apoptotic
      PBMCs. We also discuss pre-clinical studies with apoptotic cell-based therapies
      and regulatory issues that have to be considered when conducting clinical trials
      using cell secretome-based products. This should allow the reader to envision
      PBMC secretome-based therapies as alternatives to all other forms of cell-based
      therapies.

PMID- 27696128
TI  - Regression analysis of current status data in the presence of a cured subgroup
      and dependent censoring.
AB  - This paper discusses regression analysis of current status data, a type of
      failure time data where each study subject is observed only once, in the presence
      of dependent censoring. Furthermore, there may exist a cured subgroup, meaning
      that a proportion of study subjects are not susceptible to the failure event of
      interest. For the problem, we develop a sieve maximum likelihood estimation
      approach with the use of latent variables and Bernstein polynomials. For the
      determination of the proposed estimators, an EM algorithm is developed and the
      asymptotic properties of the estimators are established. Extensive simulation
      studies are conducted and indicate that the proposed method works well for
      practical situations. A motivating application from a tumorigenicity experiment
      is also provided.

PMID- 27696127
TI  - A dyadic multiple mediation model of patient and spouse stressors predicting
      patient dietary and exercise adherence via depression symptoms and diabetes self
      efficacy.
AB  - Using dyadic data from 117 married couples in which one partner was diagnosed
      with Type 2 diabetes, the purpose of this study was to determine whether a number
      of specific patient and spouse stressors (chronic life stress, diabetes-specific
      stress, and physical health stress in the form of the number of comorbidities)
      were associated with Type 2 diabetes patients' dietary and exercise adherence
      through two potentially modifiable patient and spouse factors-depression symptoms
      and diabetes self-efficacy. We found that patient and spouse stressors,
      particularly patient and spouse diabetes stress and the number of patient
      comorbidities, were related to patient dietary and exercise adherence through
      patient depression symptoms and both patient and spouse diabetes self-efficacy.
      These conclusions were strengthened by incorporating a number of relevant control
      variables in our models and by testing four alternative models which supported
      our proposed model. These results are important because they provide further
      evidence of the significant role spouses' play in managing diabetes and they
      provide diabetes educators and clinicians with specific targets for intervention
      programming.

PMID- 27696129
TI  - Microscopic histological characteristics of soft tissue sarcomas: analysis of
      tissue features and electrical resistance.
AB  - Tissue electrical conductivity is correlated with tissue characteristics. In this
      work, some soft tissue sarcomas (STS) excised from patients have been evaluated
      in terms of histological characteristics (cell size and density) and electrical
      resistance. The electrical resistance has been measured using the ex vivo study
      on soft tissue tumors electrical characteristics (ESTTE) protocol proposed by the
      authors in order to study electrical resistance of surgical samples excised by
      patients in a fixed measurement setup. The measurement setup includes a voltage
      pulse generator (700 V, 100 us long at 5 kHz, period 200 us) and an electrode
      with 7 needles, 20 mm-long, with the same distance arranged in a fixed hexagonal
      geometry. In the ESTTE protocol, the same voltage pulse sequence is applied to
      each different tumor mass and the corresponding resistance has been evaluated
      from voltage and current recorded by the equipment. For each tumor mass, a
      histological sample of the volume treated by means of voltage pulses has been
      taken for histological analysis. Each mass has been studied in order to identify
      the sarcoma type. For each histological sample, an image at 20* or 40* of
      magnification was acquired. In this work, the electrical resistance measured for
      each tumor has been correlated with tissue characteristics like the type, size
      and density of cells. This work presents a preliminary study to explore possible
      correlations between tissue characteristics and electrical resistance of STS.
      These results can be helpful to adjust the pulse voltage intensity in order to
      improve the electrochemotherapy efficacy on some histotype of STS.

PMID- 27696130
TI  - Uncertainty assessment of gamma-aminobutyric acid concentration of different
      brain regions in individual and group using residual bootstrap analysis.
AB  - The aim of this work is to quantify individual and regional differences in the
      relative concentration of gamma-aminobutyric acid (GABA) in human brain with in
      vivo magnetic resonance spectroscopy. Spectral editing Mescher-Garwood point
      resolved spectroscopy (MEGA-PRESS) sequence and GABA analysis toolkit (Gannet)
      were used to detect and quantify GABA in anterior cingulate cortex (ACC) and
      occipital cortex (OCC) of healthy volunteers. Residual bootstrap, a model-based
      statistical analysis technique, was applied to resample the fitting residuals of
      GABA from the Gaussian fitting model (referred to as GABA+ thereafter) in both
      individual and group data of ACC and OCC. The inter-subject coefficient of
      variation (CV) of GABA+ in OCC (20.66 %) and ACC (12.55 %) with residual
      bootstrap was lower than that of a standard Gaussian model analysis (21.58 % and
      16.73 % for OCC and ACC, respectively). The intra-subject uncertainty and CV of
      OCC were lower than that of ACC in both analyses. The residual bootstrap analysis
      thus provides a more robust uncertainty estimation of individual and group GABA+
      detection in different brain regions, which may be useful in our understanding of
      GABA biochemistry in brain and its use for the diagnosis of related
      neuropsychiatric diseases.

PMID- 27696131
TI  - Pearls: How to Reduce and Fix Comminuted Posterior Acetabular Wall Fractures.

PMID- 27696132
TI  - Letter to the Editor: Editorial: How the Words We Use Affect the Care We Deliver.

PMID- 27696134
TI  - GDPD5, a choline-generating enzyme and its novel role in tumor cell migration.

PMID- 27696133
TI  - First Record of Larval Secretions of Cochliomyia macellaria (Fabricius, 1775)
      (Diptera: Calliphoridae) Inhibiting the Growth of Staphylococcus aureus and
      Pseudomonas aeruginosa.
AB  - Maggot debridement therapy (MDT) consists on the intentional and controlled
      application of sterilized larvae of the order Diptera on necrotic skin lesions
      with the purpose of cleaning necrotic tissue and removing pathogenic bacteria.
      During MDT, a marked antimicrobial activity has been reported in literature
      specially associated with antibacterial substances from Lucilia sericata
      (Meigen); however, regarding Cochliomyia macellaria (Fabricius), little is known.
      This study aimed to evaluate in vitro inhibition of bacterial growth of
      Pseudomonas aeruginosa and Staphylococcus aureus in contact with excretions and
      secretions (ES) from C. macellaria larvae. Larval ES were extracted in sterile
      distilled water and divided in three groups: ES, containing 400 MUL of autoclaved
      ES; ES+BAC, containing 400 MUL of autoclaved ES+0.5-MUL bacterial inoculum; and
      CONT-BAC, containing 400 MUL of sterile distilled water +0.5 MUL of bacterial
      inoculum. Aliquots of each experimental group were plated by spreading onto Petri
      dishes. Seedings were made at 0, 1, 2, 4, and 12 h after the extraction of ES. In
      ES+BAC groups, inhibition of S. aureus was verified between times 1 and 2 h and
      P. aeruginosa was inhibited between 0 and 4 h. There was no growth observed in
      any ES group. In the CONT-BAC groups, the number of colonies from time 4 h became
      countless for S. aureus and decreased for P. aeruginosa. As reported in the
      literature, we note here that ES have excellent bactericidal activity for both
      gram-positive and gram-negative bacteria, and this study shows for the first time
      the action of the bactericidal activity of exosecretions of C. macellaria against
      S. aureus and P. aeruginosa.

PMID- 27696135
TI  - Acrolein increases macrophage atherogenicity in association with gut microbiota
      remodeling in atherosclerotic mice: protective role for the polyphenol-rich
      pomegranate juice.
AB  - The unsaturated aldehyde acrolein is pro-atherogenic, and the polyphenol-rich
      pomegranate juice (PJ), known for its anti-oxidative/anti-atherogenic properties,
      inhibits macrophage foam cell formation, the hallmark feature of early
      atherosclerosis. This study aimed to investigate two unexplored areas of acrolein
      atherogenicity: macrophage lipid metabolism and the gut microbiota composition.
      The protective effects of PJ against acrolein atherogenicity were also evaluated.
      Atherosclerotic apolipoprotein E-deficient (apoE-/-) mice that were fed acrolein
      (3 mg/kg/day) for 1 month showed significant increases in serum and aortic
      cholesterol, triglycerides, and lipid peroxides. In peritoneal macrophages
      isolated from the mice and in J774A.1 cultured macrophages, acrolein exposure
      increased intracellular oxidative stress and stimulated cholesterol and
      triglyceride accumulation via enhanced rates of their biosynthesis and over
      expression of key regulators of cellular lipid biosynthesis: sterol regulatory
      element-binding proteins (SREBPs), 3-hydroxy-3-methyl-glutaryl-CoA reductase
      (HMGCR), and diacylglycerol acyltransferase1 (DGAT1). Acrolein-fed mice
      demonstrated a major shift in the gut microbiota composition, including a
      significant phylum-level change in increased Firmicutes and decreased
      Bacteroidetes. At the family level, acrolein significantly increased the
      prevalence of Ruminococcaceae and Lachnospiraceae of which the Coprococcus genus
      was significantly and positively correlated with serum, aortic and macrophage
      lipid levels and peroxidation. The pro-atherogenic effects of acrolein on serum,
      aortas, macrophages, and the gut microbiota were substantially abolished by PJ.
      In conclusion, these findings provide novel mechanisms by which acrolein
      increases macrophage lipid accumulation and alters the gut microbiota composition
      in association with enhanced atherogenesis. Moreover, PJ was found as an
      effective strategy against acrolein atherogenicity.

PMID- 27696136
TI  - Contemplative Intervention Reduces Physical Interventions for Children in
      Residential Psychiatric Treatment.
AB  - This research explored the effectiveness of a manualized contemplative
      intervention among children receiving intensive residential psychiatric care. Ten
      children with severe psychiatric disabilities received 12 sessions (30-45 min) of
      "Mindful Life: Schools" (MLS) over the course of a month. Facility-reported data
      on the use of physical intervention (i.e., seclusions and restraints) were
      analyzed. Acceptability questionnaires and broad-band behavioral questionnaire
      data were also collected from children and their primary clinicians. Robust
      logistic regression analyses were conducted on person-period data for the 10
      children to explore the timing of incidents resulting in the use of physical
      intervention. Incidents within each person-period were regressed on indicators of
      days of contemplative practice and days without contemplative practice. Results
      indicated that during the 24-h period following MLS class, relative to a
      comparison 24-h period, children had significantly reduced odds of receiving a
      physical intervention (OR = 0.3; 95 % CI 0.2, 0.5; p < 0.001). Behavioral
      questionnaires did not indicate significant contemplative intervention effects
      (ps >0.05), and MLS was found to be generally acceptable in this population and
      setting. These data indicate that contemplative practices acutely reduced the
      utilization of physical interventions. Clinicians seeking to implement
      preventative strategies to reduce the necessity of physical intervention in
      response to dangerous behavior should consider contemplative practices. Those
      wishing to empirically evaluate the effectiveness of contemplative practices
      should consider evaluating objective measures, such as utilization of physical
      intervention strategies, as oppose to subjective reports.

PMID- 27696137
TI  - Cross-Sectional Survey on the Dengue Knowledge, Attitudes and Preventive
      Practices Among Students and Staff of a Public University in Malaysia.
AB  - Behavioural impact programmes are especially effective for dengue control and
      prevention. Universities are key settings for health promotion, so understanding
      factors that influence the practice of dengue prevention within a university
      community becomes important. This study aimed to examine the factors affecting
      dengue knowledge, attitude and preventive practices amongst students and staff of
      a public university. A cross-sectional survey study was conducted in Kuala
      Lumpur, Malaysia. A total of 372 students and staff of the NDUM were recruited by
      stratified sampling method. Data were collected via self-administered pre-tested
      structured questionnaires covering socio-demography and dengue KAP. Data were
      analysed descriptively. For bivariate analysis, Chi square test was applied. To
      explore the factors independently associated with the practice of dengue
      prevention, a logistic regression model was introduced. Overall, the participants
      had moderate dengue-related knowledge, good attitudes and good preventive
      practices. The majority had misconceptions about mosquito biting habits (83.8 %),
      seasonality of dengue epidemics (73.2 %), and mosquito breeding sites (70.3 %).
      Staff were more likely to have good dengue-related knowledge (p < 0.001) and
      attitudes (p = 0.008) than students. There was statistically significant positive
      association between the level of dengue knowledge and monthly average household
      income (p = 0.008), age (p < 0.001) and education (p < 0.001). Having good
      attitudes towards dengue was associated with being a non-Malay (p = 0.034),
      having higher monthly average household income (p = 0.047) and tertiary education
      (p < 0.001). In regression analysis, only dengue knowledge and dengue attitudes
      were significantly and positively associated with practice of dengue prevention.
      Dengue preventive strategies amongst university students and staff should focus
      on maintaining good dengue-related preventive practices. Educational campaigns
      should mainly target students, young staff members, and those with lower level of
      education and income.

PMID- 27696138
TI  - In Silico Template Selection of Short Antimicrobial Peptide Viscotoxin for
      Improving Its Antimicrobial Efficiency in Development of Potential Therapeutic
      Drugs.
AB  - Rapid increase in antibiotic resistance has posed a worldwide threat, due to
      increased mortality, morbidity, and expenditure caused by antibiotic-resistant
      microbes. Recent development of the antimicrobial peptides like viscotoxin (Vt)
      has been successfully comprehended as a substitute for classical antibiotics. A
      structurally stable peptide, Vt can enhance antimicrobial property and can be
      used for various developmental purposes. Thus, structural stability among the
      antimicrobial peptides, Vt A1 (3C8P), A2 (1JMN), A3 (1ED0), B (1JMP), and C
      (1ORL) of Viscus album was computationally analyzed. In specific, the static
      confirmation of VtA3 showed high number of intramolecular interactions, along
      with an increase in hydrophobicity than others comparatively. Further,
      conformational sampling was used to analyze various geometrical parameters such
      as root mean square deviation, root mean square fluctuation, radius of gyration,
      and ovality which also revealed the structural stability of VtA3. Moreover, the
      statistically validated contours of surface area, lipophilicity, and distance
      constraints of disulfide bonds also supported the priority of VtA3 with respect
      to stability. Finally, the functional activity of peptides was accessed by
      computing their free energy of membrane association and membrane interactions,
      which defined VtA3 as functionally stable. Currently, peptide-based antibiotics
      and nanoparticles have attracted the pharmaceutical industries for their
      potential therapeutic applications. Thereby, it is proposed that viscotoxin A3
      (1ED0) could be used as a preeminent template for scaffolding potentially
      efficient antimicrobial peptide-based drugs and nanomaterials in future.

PMID- 27696139
TI  - Promoting Tag Removal of a MBP-Fused Integral Membrane Protein by TEV Protease.
AB  - Tag removal is a prerequisite issue for structural and functional analysis of
      affinity-purified membrane proteins. The present study took a MBP-fused membrane
      protein, MrpF, as a model to investigate the tag removal by TEV protease.
      Influences of the linking sequence between TEV cleavage site and MrpF on protein
      expression and predicted secondary structure were investigated. The steric
      accessibility of TEV protease to cleavage site of MBP-fused MrpF was explored. It
      was found that reducing the size of hydrophilic group of detergents and/or
      extending the linking sequence between cleavage site and target protein can
      significantly improve the accessibility of the cleavage site and promote tag
      removal by TEV protease.

PMID- 27696140
TI  - Use of Swine Wastewater as Alternative Substrate for Mycelial Bioconversion of
      White Rot Fungi.
AB  - Seven white rot fungal species were tested for growth as mycelia using swine
      wastewater (SW), an agro-waste with tremendous environmental footprint, as the
      sole nutrient source. The SW contained high concentrations of carbon and nitrogen
      components, which could support nutritional requirements for mycelial growth. Out
      of the seven species, Pleurotus ostreatus and Hericium erinaceus were
      successfully cultivated on the SW medium using solid-state fermentation. Response
      surface methodology was employed to determine the combination of pH, temperature
      (T), and substrate concentration (C) that maximizes mycelial growth rate (Kr) for
      the two species. The optimum condition was estimated as pH = 5.8, T = 28.8 
      degrees C, and C = 11.2 g chemical oxygen demand (COD)/L for P. ostreatus to
      yield Kr of 11.0 mm/day, whereas the greatest Kr (3.1 mm/day) was anticipated at
      pH = 4.6, T = 25.5  degrees C, and C = 11.9 g COD/L for H. erinaceus. These Kr
      values were comparable to growth rates obtained using other substrates in the
      literature. These results demonstrate that SW can be used as an effective
      substrate for mycelial cultivation of the two white rot fungal species,
      suggesting an alternative method to manage SW with the production of potentially
      valuable biomass.

PMID- 27696141
TI  - Recovery of Phenolic Acid and Enzyme Production from Corn Silage Biologically
      Treated by Trametes versicolor.
AB  - Corn silage is used as high-energy forage for dairy cows and more recently for
      biogas production in a process of anaerobic co-digestion with cow manure. In this
      work, fresh corn silage after the harvest was used as a substrate in solid-state
      fermentations with T. versicolor with the aim of phenolic acid recovery and
      enzyme (laccase and manganese peroxidase) production. During 20 days of
      fermentation, 10.4-, 3.4-, 3.0-, and 1.8-fold increments in extraction yield of
      syringic acid, vanillic acid, p-hydroxybenzoic acid, and caffeic acid,
      respectively, were reached when compared to biologically untreated corn silage.
      Maximal laccase activity was gained on the 4th day of fermentation (V.A. = 180.2
      U/dm3), and manganese peroxidase activity was obtained after the 3rd day of
      fermentation (V.A. = 30.1 U/dm3). The addition of copper(II) sulfate as inducer
      during solid state fermentation resulted in 8.5- and 7-fold enhancement of
      laccase and manganese peroxidase activities, respectively. Furthermore, the
      influence of pH and temperature on enzyme activities was investigated. Maximal
      activity of laccase was obtained at T = 50  degrees C and pH = 3.0, while
      manganese peroxidase is active at temperature range T = 45-70  degrees C with the
      maximal activity at pH = 4.5.

PMID- 27696143
TI  - Erratum to: Shiitake Mushroom Dermatitis: A Review.

PMID- 27696142
TI  - Contemporary Controversies in Digoxin Use in Systolic Heart Failure.
AB  - Digoxin remains one of the oldest therapies for heart failure; however, its
      safety and efficacy have been controversial since its initial use. Questions that
      remain include the clinical efficacy of digoxin when added to contemporary
      medical therapy, when and if it should be added, and how to minimize adverse
      effects. In this review, we will summarize recent data on the use of digoxin in
      systolic heart failure and address some of the controversies regarding the role
      of digoxin in the modern era of heart failure treatment.

PMID- 27696145
TI  - A Positive Generation Effect on Memory for Auditory Context.
AB  - Self-generation of information during memory encoding has large positive effects
      on subsequent memory for items, but mixed effects on memory for contextual
      information associated with items. A processing account of generation effects on
      context memory (Mulligan in Journal of Experimental Psychology: Learning, Memory,
      and Cognition, 30(4), 838-855, 2004; Mulligan, Lozito, & Rosner in Journal of
      Experimental Psychology: Learning, Memory, and Cognition, 32(4), 836-846, 2006)
      proposes that these effects depend on whether the generation task causes any
      shift in processing of the type of context features for which memory is being
      tested. Mulligan and colleagues have used this account to predict various
      negative effects of generation on context memory, but the account also predicts
      positive generation effects under certain circumstances. The present experiment
      provided a critical test of the processing account by examining how generation
      affected memory for auditory rather than visual context. Based on the processing
      account, we predicted that generation of rhyme words should enhance processing of
      auditory information associated with the words (i.e., voice gender), whereas
      generation of antonym words should have no effect. These predictions were
      confirmed, providing support to the processing account.

PMID- 27696144
TI  - Lower Bone Mineral Density at the Hip and Lumbar Spine in People with Psychosis
      Versus Controls: a Comprehensive Review and Skeletal Site-Specific Meta-analysis.
AB  - It remains unclear if differences in bone mineral density (BMD) exist at
      different skeletal sites between people with schizophrenia and age- and sex
      matched healthy controls (HCs). Major databases were searched from inception
      until February 2016 for studies measuring BMD using dual-energy X-ray
      absorptiometry (DXA) at any skeletal site in individuals with schizophrenia. Ten
      studies investigating 827 people with schizophrenia (55.4 % female, 33.8 +/- 9.7
      years) and 1379 HCs (58.7 % female, 34.7 +/- 9.1 years) were included. People
      with schizophrenia had significantly reduced BMD at the lumbar spine
      (standardised mean difference adjusted for publication bias (SMD) = -0.950 (95 %
      CI = -1.23 to -0.66, fail-safe number = 825) and hip (SMD = -0.534, 95 % CI = 
      0.876 to -0.192, fail-safe number = 186). A higher proportion of
      hyperprolactinaemia (beta = -0.0102, p < 0.0001) and smokers (beta = -0.0099, p =
      0.02) moderated a larger reduced BMD at the lumbar spine. Further research is
      required to investigate if low bone mass and fractures can be prevented in people
      with schizophrenia.

PMID- 27696146
TI  - Redox and Organic Post-Annealing Chemical Processes Impacting the Fluorescence of
      N V - Centers into Nanodiamonds : A Competitive Process Between Exfoliation and
      Functionalisation.
AB  - Among the several aspects involved into the synthesis of monocharged nitrogene
      vacancy N V - colored centers produced into nanodiamonds ND, the post-annealing
      cleaning process, such as sulfo-nitric acid cleaning or thermal oxidation under
      acid conditions, can be seen as a factor impacting the optical response of these
      N V - colored centers. A significative difference of optical response is in fact
      noticed modifying the post-annealing treatment conditions, between a pure
      oxidative treatment at room temperature and a mixed-process including oxidation
      and thermal activation. Specific chemical processes and surface chemical aspects
      are proposed to explain the optical signals obtained by fluorescence. Some
      chemical pathways are then found more efficient than others to limit the
      fluorescence quenching of these colored N V - emitters.

PMID- 27696147
TI  - Relapsing Polychondritis: A Review and Guide for the Dermatologist.
AB  - Relapsing polychondritis, or RP, is a rare connective tissue disease
      characterized by relapsing-remitting destructive inflammation of the
      cartilaginous and other proteoglycan-rich structures in the body. Given the
      relatively low incidence of RP, a concise clinically relevant guide, focusing on
      the cutaneous manifestations of this serious disease, is lacking. In this review,
      we provide the dermatologist with an approach to diagnosing RP and a guide to its
      initial work-up, and management. We close with an overview of the currently
      available treatment modalities for RP.

PMID- 27696148
TI  - Frequency and analysis of non-clinical errors made in radiology reports using the
      National Integrated Medical Imaging System voice recognition dictation software.
AB  - BACKGROUND: Voice recognition (VR) dictation of radiology reports has become the
      mainstay of reporting in many institutions worldwide. Despite benefit, such
      software is not without limitations, and transcription errors have been widely
      reported. AIM: Evaluate the frequency and nature of non-clinical transcription
      error using VR dictation software. METHODS: Retrospective audit of 378 finalised
      radiology reports. Errors were counted and categorised by significance, error
      type and sub-type. Data regarding imaging modality, report length and dictation
      time was collected. RESULTS: 67 (17.72 %) reports contained >=1 errors, with 7
      (1.85 %) containing 'significant' and 9 (2.38 %) containing 'very significant'
      errors. A total of 90 errors were identified from the 378 reports analysed, with
      74 (82.22 %) classified as 'insignificant', 7 (7.78 %) as 'significant', 9 (10 %)
      as 'very significant'. 68 (75.56 %) errors were 'spelling and grammar', 20 (22.22
      %) 'missense' and 2 (2.22 %) 'nonsense'. 'Punctuation' error was most common sub
      type, accounting for 27 errors (30 %). Complex imaging modalities had higher
      error rates per report and sentence. Computed tomography contained 0.040 errors
      per sentence compared to plain film with 0.030. Longer reports had a higher error
      rate, with reports >25 sentences containing an average of 1.23 errors per report
      compared to 0-5 sentences containing 0.09. CONCLUSION: These findings highlight
      the limitations of VR dictation software. While most error was deemed
      insignificant, there were occurrences of error with potential to alter report
      interpretation and patient management. Longer reports and reports on more complex
      imaging had higher error rates and this should be taken into account by the
      reporting radiologist.

PMID- 27696150
TI  - In Vitro andIn Vivo induction of bone formation using a recombinant adenoviral
      vector carrying the human BMP-2 gene.
AB  - It has been well established that bone morphogenetic protein-2 (BMP-2) can induce
      bone formation bothin vivo andin vitro, although high concentrations (up to
      milligrams) of BMP-2 have been required to achieve this effectin vivo. Further,
      clinical applications are usually limited to a single dose at the time of
      implantation. In an attempt to prolong the transforming effect of BMP-2 we used a
      recombinant adenoviral vector carrying the human BMP-2 gene (Adv-BMP2) to
      transduce marrow-derived mesenchymal stem cells (MSC) of skeletally mature male
      New Zealand white rabbits. The pluripotential MSC were incubated with Adv-BMP2
      overnight followed by culture in growth medium for 1 week. Assays on tissue
      cultures demonstrated that these Adv-BMP2 transduced MSC produced BMP-2 protein,
      differentiated into an osteoprogenitor line, and induced bone formationin vitro.
      These MSC had increased alkaline phosphatase activity, increased expression of
      type I collagen, osteopontin, and osteocalcin mRNA, and induced matrix
      mineralization compared with both nontransduced cells and cells transduced with a
      control adenoviral construct. To analyze the osteogenic potentialin vivo, Adv
      BMP2-transduced MSC were autologously implanted into the intertransverse process
      space between L5 and L6 of the donor rabbits. The production of new bone was
      demonstrated by radiographic examination 4 weeks later in areas implanted with
      cells transduced with Adv-BMP2, whereas no bone was evident at sites implanted
      with cells transduced with the control adenoviral construct. Histological
      examination further confirmed the presence of new bone formation. These
      accumulated data indicate that it is possible to successfully transduce
      mesenchymal stem cells with a recombinant adenoviral vector carrying the gene for
      BMP-2 such that these cells will produce BMP-2, differentiate into an
      osteoprogenitor line, and induce bone formation bothin vitro andin vivo.
      Moreover, incubation of the Adv-BMP2-transduced cells for an additional 7 days in
      culture before transplantation enhances the success rate in bone formation (three
      out of three) as compared with our previous report (one out of five, Calcif
      Tissue Int 63:357-360, 1998).

PMID- 27696149
TI  - Generation of IL10 and TGFB1 coexpressed mice displaying resistance to ovalbumin
      induced asthma.
AB  - Asthma is a common chronic inflammatory disease in the airways with wide
      prevalence, and it is thought to be caused by the combinational factors in
      environment and genetics. A large body of studies has suggested that cell
      immunity played a vital role in regulating the airway hyperreactivity (AHR) and
      inflammation. Therefore, we here developed a mouse model of asthma by
      microinjecting the pronucleus with a vector spontaneously coding human IL10 and
      TGFB1 gene to explore the possible interaction between these two potent molecules
      during asthma progression. From the total 35 newborn mice, we successfully
      obtained 3 founders expressing exogenous genes. In the transgenic mice, we
      observed profoundly enhanced expression of IL10 and TGFB1. In the condition of
      ovalbumin challenge, transgenic mice displayed a 1.9-fold higher MCh50 score than
      wild-type counterparts, indicating reminiscent AHR. Meanwhile, a three-fold
      decrease of cell counts in bronchoalveolar lavage fluid (BALF) was recorded as
      well. These results suggested that IL10 and TGFB1 cooperatively protected the
      respiratory system in response to antigenic stimulus. To interrogate the
      respective behaviors of the two genes, we quantified the expression of downstream
      genes in IL10 signaling or TGFB1 signaling. We observed that the examined genes
      in IL10 signaling were significantly repressed, especially IL5, which showed 5.4
      fold decreased expression. Most genes were not altered in TGFB1 signaling, and
      the production of endogenous TGFB1 was significantly inhibited. These evidences
      collectively proved that the activation of IL0 and TGFB1 protected the host from
      antigen-induced asthma, possibly through IL10 signaling. This study shed some
      light on the modulations of IL10 and TGFB1, and related networks to asthma
      progression.

PMID- 27696151
TI  - Baseline expression and effect of TGF-beta1 on Type I and III collagen mRNA and
      protein synthesis in human odontoblasts and pulp cellsIn Vitro.
AB  - Since growth factors have been suggested to regulate dentin collagen formation in
      response to external irritation, we investigated the effect of TGF-beta1 on
      proalpha1(I) collagen mRNA expression in cultured mature human odontoblasts and
      pulpal fibroblasts, as well as cultured human pulp tissue, using quantitative
      PCR. Cultured gingival fibroblasts (GF) and osteoblasts (OB) served as controls.
      Also, type I collagen synthesis in cultured odontoblasts and pulp tissue, as well
      as type III collagen synthesis in odontoblasts, were studied by measuring
      respective procollagen (PINP and PIIINP) secretion into culture media with
      radioimmunoassay (RIA). Odontoblasts expressed significantly higher basic level
      of type I collagen mRNA than pulp tissue or pulp fibroblasts in culture, but
      markedly lower level than GF and OB cells. TGF-beta1 (10 ng/ml) had negligible
      effects on type I collagen mRNA expression or PINP synthesis in cultured
      odontoblasts and pulp tissue, and PIIINP synthesis in the odontoblasts. In PF
      cells, the effect of TGF-beta1 depended on culturing conditions; a 6-fold
      increase in mRNA expression was observed using serum-free medium but no effect
      was seen in the cells cultured with 10% FBS. In contrast, GF cells serving as
      controls were not markedly affected by the culture conditions, with 2-3-fold
      increase in mRNA expression by TGF-beta1. These experiments demonstrate that
      mature human odontoblasts are capable of synthesizing type III collagen protein,
      and that TGF-beta1 has negligible effect on mature human odontoblast and pulp
      tissue collagen expression.

PMID- 27696155
TI  - Employing an open-source tool to assess astrocyte tridimensional structure.
AB  - Astrocytes display important features that allow them to maintain a close dialog
      with neurons, ultimately impacting brain function. The complex morphological
      structure of astrocytes is crucial to the role of astrocytes in brain networks.
      Therefore, assessing morphologic features of astrocytes will help provide
      insights into their physiological relevance in healthy and pathological
      conditions. Currently available tools that allow the tridimensional
      reconstruction of astrocytes present a number of disadvantages, including the
      need for advanced computational skills and powerful hardware, and are either time
      consuming or costly. In this study, we optimized and validated the FIJI-ImageJ,
      Simple Neurite Tracer (SNT) plugin, an open-source software that aids in the
      reconstruction of GFAP-stained structure of astrocytes. We describe (1) the
      loading of confocal microscopy Z-stacks, (2) the selection criteria, (3) the
      reconstruction process, and (4) the post-reconstruction analysis of morphological
      features (process length, number, thickness, and arbor complexity). SNT allows
      the quantification of astrocyte morphometric parameters in a simple, efficient,
      and semi-automated manner. While SNT is simple to learn, and does not require
      advanced computational skills, it provides reproducible results, in different
      brain regions or pathophysiological states.

PMID- 27696156
TI  - Dendritic-branching angles of pyramidal neurons of the human cerebral cortex.
AB  - In this article, we analyze branching angles of the basal dendrites of pyramidal
      neurons of layers III and V of the human temporal cortex. For this, we use a
      novel probability directional statistical distribution called truncated von Mises
      distribution that is able to describe more accurately the dendritic-branching
      angles than the previous proposals. Then, we perform comparative studies using
      this statistical method to determine similarities and/or differences between
      branches and branching angles that belong to different cortical layers and
      regions. Using this methodology, we found that common design principles exist and
      govern the patterns found in the different branches that compose the basal
      dendrites of human pyramidal cells of the temporal cortex. However, particular
      differences were found between supra and infragranular cells. Furthermore, we
      compared the branching angles of human layer III pyramidal neurons with data
      obtained in the previous studies in layer III of both the rat somatosensory
      cortex and of several cortical areas of the mouse. Finally, we study the
      branching angle differences between the humans that compose our data.

PMID- 27696157
TI  - Prolonged fibroblast growth factor 19 response in patients with primary
      sclerosing cholangitis after an oral chenodeoxycholic acid challenge.
AB  - BACKGROUND: Bile salts likely contribute to liver injury in patients with primary
      sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast
      growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective
      potential as it suppresses de novo bile salt synthesis. Here, we evaluated the
      bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients. METHODS:
      Fasted patients with PSC (n = 12) and PBC (n = 10), and healthy controls (HC; n =
      10) were orally challenged with the natural FXR agonist chenodeoxycholic acid
      (CDCA 15 mg/kg). Blood was sampled hourly until 8 h afterwards. Serum FGF19 and
      bile salt excursions were determined. Serum levels of 7alpha-hydroxy-4-cholesten
      3-one (C4), reflecting bile salt synthesis, were measured as a biomarker of FGF19
      response. RESULTS: Baseline serum FGF19 levels were comparable between groups,
      while fasted bile salt levels in PSC patients were elevated. Upon CDCA challenge,
      HC and PBC patients showed a serum FGF19 peak after 4 h followed by a decline.
      PSC patients showed a prolonged and elevated serum FGF19 response up to 8 h,
      combined with a sustained serum elevation of CDCA and other bile salts. In
      general, C4 levels declined following FGF19 elevation. In PSC patients with less
      favorable prognosis, baseline C4 levels were drastically suppressed and did not
      further decline. CONCLUSION: Following an oral CDCA challenge, PSC patients
      showed an impaired clearance of CDCA and a prolonged serum FGF19 response. FXR
      agonist therapy in PSC could cause prolonged exposure to elevated levels of
      FGF19, and we propose careful monitoring for detrimental side effects in patient
      studies.

PMID- 27696158
TI  - Vortex-assisted ionic liquid-based dispersive liquid-liquid microextraction for
      assessment of chromium species in artificial saliva extract of different chewing
      tobacco products.
AB  - A novel dispersive liquid-liquid microextraction (ILDLLMUE) method using an
      extracting solvent (ionic liquid) and dispersant (Triton X-114) was developed for
      the separation and preconcentration of hexavalent chromium (Cr6+) in artificial
      saliva extract (ASE) of chewing tobacco products, gutkha, and mainpuri (n = 23).
      In the proposed method, the extraction of Cr6+ was accomplished by using ammonium
      pyrrolidinedithiocarbamate (APDC) as complexing agent and 1-butyl-3
      methylimidazolium hexafluorophosphate [C4MIM] [PF6] as extracting solvent. The
      tiny droplet of metal chelate was then dispersed into TX-114 emulsion, using
      vortex mixer. Various parameters such as concentration of APDC, pH of the
      solution, volume of [C4MIM] [PF6], and TX-114 as well as extraction time were
      studied. Under the most favorable conditions, the limit of detection was found to
      be 0.068 MUg/L with the relative standard deviation <5 %. The enrichment factor
      of developed method was found as 62.5, and method has been effectively applied
      for the analysis of Cr species in artificial saliva extract of gutkha and
      mainpuri products. The Cr6+ was quantitatively recovered (<97 %) under optimal
      conditions, while the recovery of trivalent specie (Cr3+), at the same
      experimental conditions, was observed to be <5 %. The Cr3+ was determined by the
      difference of total Cr and Cr6+ in artificial saliva extract of selected STP.
      Health risks associated with the intake of total Cr in gutkha and mainpuri were
      assessed in terms of estimated daily intake, such as carcinogenic and
      noncarcinogenic risks. Estimated daily intake of Cr via chewing 10 g/day of
      gutkha and mainpuri was found to be below the maximum tolerable daily intake,
      whereas the calculated risk of cancer for Cr was observed in the acceptable range
      of 10E-6-10E-4, except some brands of gutkha. Graphical Abstract ?.

PMID- 27696159
TI  - Erratum to: Accumulation of Cr, Cd, Pb, Cu, and Zn by plants in tanning sludge
      storage sites: opportunities for contamination bioindication and
      phytoremediation.

PMID- 27696161
TI  - Impact of untreated urban waste on the prevalence and antibiotic resistance
      profiles of human opportunistic pathogens in agricultural soils from Burkina
      Faso.
AB  - This study examined the long-term effects of the landfill disposal of untreated
      urban waste for soil fertilization on the prevalence and antibiotic resistance
      profiles of various human opportunistic pathogens in soils from Burkina Faso.
      Samples were collected at three sites in the periphery of Ouagadougou during two
      campaigns in 2008 and 2011. At each site, amendment led to changes in physico
      chemical characteristics as shown by the increase in pH, CEC, total C, total N,
      and metal contents. Similarly, the numbers of total heterotrophic bacteria were
      higher in the amended fields than in the control ones. No sanitation indicators,
      i.e., coliforms, Staphylococci, and Enterococci, were detected. Pseudomonas
      aeruginosa and Burkholderia cepacia complex (Bcc) were detected at a low level in
      one amended field. Stenotrophomonas maltophilia was detected from both campaigns
      at the three sites in the amended fields and only once in an unamended field.
      Diversity analysis showed some opportunistic pathogen isolates to be closely
      related to reference clinical strains responsible for nosocomial- or community
      acquired infections in Northern countries. Antibiotic resistance tests showed
      that P. aeruginosa and Bcc isolates had a wild-type phenotype and that most S.
      maltophilia isolates had a multi-drug resistance profile with resistance to 7 to
      15 antibiotics. Then we were able to show that amendment led to an increase of
      some human opportunistic pathogens including multi-drug resistant isolates.
      Although the application of untreated urban waste increases both soil organic
      matter content and therefore soil fertility, the consequences of this practice on
      human health should be considered.

PMID- 27696162
TI  - Effect of carbon sources on the aggregation of photo fermentative bacteria
      induced by L-cysteine for enhancing hydrogen production.
AB  - Poor flocculation of photo fermentative bacteria resulting in continuous biomass
      washout from photobioreactor is a critical challenge to achieve rapid and stable
      hydrogen production. In this work, the aggregation of Rhodopseudomonas faecalis
      RLD-53 was successfully developed in a photobioreactor and the effects of
      different carbon sources on hydrogen production and aggregation ability were
      investigated. Extracellular polymeric substances (EPS) production by R. faecalis
      RLD-53 cultivated using different carbon sources were stimulated by addition of L
      cysteine. The absolute zeta potentials of R. faecalis RLD-53 were considerably
      decreased with addition of L-cysteine, and aggregation barriers based on DLVO
      dropped to 15-43 % of that in control groups. Thus, R. faecalis RLD-53
      flocculated effectively, and aggregation abilities of strain RLD-53 cultivated
      with acetate, propionate, lactate and malate reached 29.35, 32.34, 26.07 and
      24.86 %, respectively. In the continuous test, hydrogen-producing activity was
      also promoted and reached 2.45 mol H2/mol lactate, 3.87 mol H2/mol propionate and
      5.10 mol H2/mol malate, respectively. Therefore, the aggregation of R. faecalis
      RLD-53 induced by L-cysteine is independent on the substrate types, which ensures
      the wide application of this technology to enhance hydrogen recovery from
      wastewater dominated by different organic substrates.

PMID- 27696160
TI  - Studies on photodegradation process of psychotropic drugs: a review.
AB  - Consumption of psychotropic drugs is still increasing, especially in high-income
      countries. One of the most crucial consequences of this fact is significant
      release of them to the environment. Considerable amounts of atypical
      antipsychotics, benzodiazepines, antidepressants, and their metabolites were
      detected in river, lake, and sea water, as well as in tissues of aquatic
      organisms. Their ecotoxicity was proved by numerous studies. It should be noticed
      that interaction between psychotropic pharmaceuticals and radiation may lead to
      formation of potentially more toxic intermediates. On the other hand, photo
      assisted wastewater treatment methods can be used as an efficient way to
      eliminate them from the environment. Many methods based on photolysis and
      photocatalysis were proposed and developed recently; nevertheless, the problem is
      still unsolved. However, according to recent studies, photocatalysis could be
      considered as the most promising and far more effective than regular photolysis.
      An overview on photolytic as well as homogenous and heterogeneous photocatalytic
      degradation methods with the use of various catalysts is presented. The
      photostability and phototoxicity of pharmaceuticals were also discussed. Various
      analytical methods were used for the photodegradation research, and this issue
      was also compared and summarized. Use of high-resolution multistage mass
      spectrometry (Q-TOF, ion trap, Orbitrap) was suggested. The combined techniques
      such as LC-MS, GC-MS, and LC-NMR, which enable qualitative and quantitative
      analyses in one run, proved to be the most valuable in this case. Assembling of
      MS/MS spectra libraries of drug molecules and their phototransformation products
      was identified as the future challenge.

PMID- 27696164
TI  - Suppression of PCDD/Fs during thermal desorption of PCBs-contaminated soil.
AB  - Thermal treatment of polychlorinated biphenyls (PCBs) contaminated soil was shown
      in earlier work to generate new PCBs, as well as polychlorinated dibenzo-p
      dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). In this study, this
      thermal desorption was conducted with addition of three distinct inhibitors,
      including ammonium sulphate, urea and calcium oxide, to inhibit the formation of
      PCDDs and PCDFs when remediating PCBs-contaminated soil. Experiments were
      conducted for 40 min at 400  degrees C after adding 1 wt.% of inhibitor. Both the
      total PCDD/Fs and international toxic equivalent quantity (I-TEQ) reduced when
      inhibitors were introduced. Of the three compounds tested, CaO shows the highest
      inhibition efficiency, 92.2 % for total PCDD/Fs and 95.6 % for I-TEQ. The amount
      of CaO added also influences the suppression efficiency of PCDD/Fs. These results
      suggest that promoting desorption and destruction of precursors is probably the
      mechanism of suppression.

PMID- 27696163
TI  - Anxiety and memory deficits induced by tannery effluent in C57BL/6J female mice.
AB  - This study aimed to evaluate the behavior of female C57Bl/6J mice exposed to
      tannery effluents diluted in drinking water. Female mice were divided into a
      control group, in which the animals received only drinking water, and
      experimental groups, which received raw tannery effluent in 7.5 and 15 %
      concentrations diluted in water (period of 60 days). In the last experimental
      week, the mice (in diestrus phase) were subjected to different behavioral tests:
      elevated plus-maze, open-field test, forced swim test, and object recognition
      test. Our data demonstrated that exposure to tannery effluent increased the
      anxiety index of animals and decreased the locomotion ratio in the central
      quadrants/total, indicating an increase in anxiety-like behavior. Regarding the
      forced swim test, we did not observe changes in the evaluated behaviors. There
      were no statistically significant differences in the recognition index of the
      novel and familiar object in the groups exposed to tannery effluent compared with
      the control group, indicating a possible influence of the constituents of tannery
      effluent on cognition. Thus, our findings support the hypothesis that effluents,
      containing neurotoxic substances, could cause behavioral disruptions in female
      C57Bl/6J mice.

PMID- 27696166
TI  - Urban biowaste-derived sensitizing materials for caffeine photodegradation.
AB  - Caffeine-photosensitized degradation has been studied in the presence of bio
      based materials derived from urban biowaste after aerobic aging. A peculiar
      fraction (namely bio-based substances (BBSs)), soluble in all the pH range, has
      been used as photosensitizing agent. Several caffeine photodegradation tests have
      been performed, and positive results have been obtained in the presence of BBSs
      and H2O2, without and with additional Fe(II) (photo-Fenton-like process).
      Moreover, hybrid magnetite-BBS nanoparticles have been synthesized and
      characterized, in order to improve the sensitizer recovery and reuse after the
      caffeine degradation. In the presence of such nanoparticles and H2O2 and Fe(II),
      the complete caffeine degradation has been attained in very short time. Both
      homogeneous and heterogeneous processes were run at pH = 5, milder condition
      compared to the classic photo-Fenton process.

PMID- 27696165
TI  - Glial markers and emotional memory in rats following acute cerebral
      radiofrequency exposures.
AB  - The widespread mobile phone use raises concerns on the possible cerebral effects
      of radiofrequency electromagnetic fields (RF EMF). Reactive astrogliosis was
      reported in neuroanatomical structures of adaptive behaviors after a single RF
      EMF exposure at high specific absorption rate (SAR, 6 W/kg). Here, we aimed to
      assess if neuronal injury and functional impairments were related to high SAR
      induced astrogliosis. In addition, the level of beta amyloid 1-40 (Abeta 1-40)
      peptide was explored as a possible toxicity marker. Sprague Dawley male rats were
      exposed for 15 min at 0, 1.5, or 6 W/kg or for 45 min at 6 W/kg. Memory,
      emotionality, and locomotion were tested in the fear conditioning, the elevated
      plus maze, and the open field. Glial fibrillary acidic protein (GFAP, total and
      cytosolic fractions), myelin basic protein (MBP), and Abeta1-40 were quantified
      in six brain areas using enzyme-linked immunosorbent assay. According to our
      data, total GFAP was increased in the striatum (+114 %) at 1.5 W/kg. Long-term
      memory was reduced, and cytosolic GFAP was increased in the hippocampus (+119 %)
      and in the olfactory bulb (+46 %) at 6 W/kg (15 min). No MBP or Abeta1-40
      expression modification was shown. Our data corroborates previous studies
      indicating RF EMF-induced astrogliosis. This study suggests that RF EMF-induced
      astrogliosis had functional consequences on memory but did not demonstrate that
      it was secondary to neuronal damage.

PMID- 27696167
TI  - Mitigation of cadmium-induced lung injury by Nigella sativa oil.
AB  - Induction of oxidative stress and inflammation are considered the primary
      mechanism of cadmium (Cd) toxicity. Nigella sativa (NS) seeds and their oil (NSO)
      have been reported to possess antioxidant and anti-inflammatory potential. This
      study was conducted to assess the protective effect of NSO on Cd-induced lung
      damage in rat. Forty adult male Wistar rats were divided equally into 4 groups.
      Animals in groups I, II, and III received 1 ml of isotonic saline
      intraperitoneally (IP), 2 mg/kg of cadmium chloride (CdCl2) dissolved in isotonic
      saline IP, and 1 ml/kg of NSO by gastric gavage, respectively. Group IV rats
      received NSO an hour prior to CdCl2 administration via the same routes and doses
      as previously described. All animals were treated for 28 days. At the end of the
      study, animals were sacrificed; lungs were harvested for histopathological
      studies using light and electron microscopy. Saline-treated and NSO-treated rats
      showed normal lung parenchyma. However, CdCl2-treated rats showed massive
      degenerative changes in alveolar epithelial lining, disrupted interalveolar
      septa, and hemolytic debris in alveoli. Rats treated with both NSO and CdCl2
      (group IV) showed amelioration of most Cd-induced lung damage with minimal
      histopathological changes in lung architecture. This study elucidates the
      protective effects of NSO on Cd-induced lung injury in rats and highlights the
      possibility of using NSO as a protective agent in individuals at high risk of Cd
      induced lung toxicity.

PMID- 27696168
TI  - Heavy metals in surface sediments of the shallow lakes in eastern China: their
      relations with environmental factors and anthropogenic activities.
AB  - The aquatic environment is affected by heavy metal pollution. This study was
      conducted to test the hypothesis that environmental factors and anthropogenic
      activities influence the distributions and the risks posed by heavy metals in
      surface sediments in shallow lakes in eastern China, which is an area affected by
      rapid urbanization, industrialization, and population growth. Total Cd, Cr, Cu,
      Ni, Pb, Se, and Zn concentrations in sediment samples were determined using
      inductively coupled plasma optical emission spectrometry. The I geo showed that
      sediments in the lakes were moderately polluted with Cr, Cu, Pb, and Zn, and the
      EF method showed that Cd and Se were significantly enriched in lakes. The heavy
      metals were found to pose moderate risks in most of the lakes, except for Gaoyou
      Lake, Honghu Lake, Poyang Lake, and Weishan Lake. The RI method indicated that
      very high risks were posed in Dongting Lake and Poyang Lake. Cd was found to pose
      much higher levels of risk than the other metals. Significant correlations were
      found between the heavy metal concentrations and the total carbon, nitrogen,
      phosphorus, and sulfur concentrations. The gross domestic product represented
      anthropogenic activities well. The gross domestic product of an area and the
      gross domestic products of primary and secondary industries in an area all had
      significant relationships with the concentrations of Cu and Pb, indicating that
      anthropogenic activities have different impacts on pollution with different heavy
      metals. The gross domestic product index was found to be a driving force behind
      the pollution of lakes with heavy metals.

PMID- 27696169
TI  - Prior Radiotherapy Does Not Affect Abdominal Wall Reconstruction Outcomes:
      Evidence from Propensity Score Analysis.
AB  - BACKGROUND: Prior abdominal wall radiotherapy (XRT) adversely affects wound
      healing, but data are limited on how prior XRT may affect abdominal wall
      reconstruction (AWR) outcomes. The purpose of this study was to determine whether
      prior abdominal wall radiotherapy is associated with a higher incidence of
      complications following AWR for a hernia or oncologic resection defect. METHODS:
      We performed a retrospective study of consecutive patients who underwent complex
      AWR using acellular dermal matrix (ADM) at a single center. We compared outcomes
      between patients who underwent prior XRT that directly involved the abdominal
      wall and those who did not receive XRT. Propensity score match-paired and
      multivariate analyses were performed. RESULTS: A total of 511 patients (130 [25.4
      %] with prior XRT; 381 [74.6 %] without prior XRT) underwent AWR with ADM for
      repair of a complex hernia or oncologic resection defect. Mean follow-up was 31.4
      months, mean XRT dose was 48.9 Gy, and mean time between XRT and reconstruction
      was 19.2 months. XRT AWR patients underwent more flap reconstructions (14.6 vs.
      5.0 %, P < 0.001) but fewer component separations (61.5 vs. 71.4 %; P = 0.036)
      than non-XRT AWR patients. The two groups had similar rates of hernia recurrence
      (8.5 vs. 9.4 %; P = 0.737) and surgical site occurrence (25.4 vs. 23.4 %; P =
      0.640). In the propensity score-matched subgroups, there were no differences in
      hernia recurrence, surgical site occurrence, and wound healing complication
      rates. CONCLUSIONS: Prior XRT does not adversely affect outcomes in AWR. However,
      surgeons should be aware of the higher likelihood of needing a soft tissue flap
      reconstruction for soft tissue replacement when performing AWR after XRT.

PMID- 27696170
TI  - KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients
      Undergoing Resection of Colorectal Liver Metastases.
AB  - BACKGROUND: The optimal tumor-free margin width remains controversial and may be
      inappropriate to investigate without considering differences in the underlying
      tumor biology. METHODS: R1 resection was defined as margin clearance less than 1
      mm. R0 resection was further divided into 3 groups: 1-4, 5-9, and >=10 mm. The
      impact of margin width on overall survival (OS) relative to KRAS status [wild
      type (wtKRAS) vs. mutated (mutKRAS)] was assessed. RESULTS: A total of 411
      patients met inclusion criteria. Median patient age was 58 years (interquartile
      range, 49.7-66.7); most patients were male (n = 250; 60.8 %). With a median
      follow-up of 28.3 months, median and 5-year OS were 69.8 months and 55.1 %. Among
      patients with wtKRAS tumors, although margin clearance of 1-4 mm or more was
      associated with improved OS compared to R1 (all P < 0.05), no difference in OS
      was observed when comparing margin clearance of 1-4 mm to the 5-9 mm and the >=10
      mm groups (all P > 0.05). In contrast, among patients with mutKRAS tumors, all
      three groups of margin clearance (1-4, 5-9, and >=10 mm) fared no better in terms
      of 5-year survival compared to R1 resection (all P > 0.05). CONCLUSIONS: While a
      1-4 mm margin clearance in patients with wtKRAS tumors was associated with
      improved survival, wider resection width did not confer an additional survival
      benefit. In contrast, margin status-including a 1 cm margin-did not improve
      survival among patients with mutKRAS tumors.

PMID- 27696171
TI  - Extending ACOSOG Z0011 to Encompass Mastectomy: What Happens Without RT?

PMID- 27696172
TI  - Clinical Significance of C-MET Overexpression and Epidermal Growth Factor
      Receptor Mutation in Platinum-Based Adjuvant Chemotherapy Outcome in Surgically
      Resected Lung Adenocarcinoma.
AB  - PURPOSE: We retrospectively assessed the role of C-MET expression and epidermal
      growth factor receptor (EGFR) mutation on survival following platinum-based
      adjuvant chemotherapy. The impact of C-MET on survival was also investigated in
      relation to EGFR mutation status. METHODS: We enrolled 311 patients with resected
      lung adenocarcinoma (high-risk stage 1B-3A), and performed immunohistochemistry
      (IHC) using C-MET- and mutant EGFR (EGFRmut)-specific antibodies in tissue
      microarrays. RESULTS: Adjuvant chemotherapy was administered to 151 patients, 96
      of whom relapsed and 85 died by the end of the study. On IHC, C-MET and EGFRmut
      were positive in 141 (45.3 %) and 88 (28.3 %) cases, respectively. On univariate
      analysis, adjuvant chemotherapy prolonged relapse-free survival (RFS) and overall
      survival (OS) in C-MET(+) patients (RFS p = 0.035; OS p = 0.013) but not in C
      MET(-) patients. On multivariate analysis, adjuvant chemotherapy was a positive
      independent prognostic factor in C-MET(+) (RFS p = 0.013; OS p = 0.006) but not
      in C-MET(-) patients. In addition, univariate analysis showed no effect of
      EGFRmut status on RFS and OS after chemotherapy, whereas multivariate analysis
      revealed that adjuvant chemotherapy increased RFS in both EGFRmut(+) and EGFRmut(
      ) patients [EGFRmut(+) p = 0.033; EGFRmut(-) p = 0.030]. C-MET was a negative
      prognostic factor for RFS (p = 0.045) and OS (p = 0.007) in the EGFRmut(-) group
      but not in the EGFRmut(+) group, on multivariate analysis. CONCLUSIONS: Our data
      indicate that patients with C-MET overexpression should be considered for
      adjuvant chemotherapy, and that C-MET negatively correlates with survival in
      patients with wild-type, but not mutant, EGFR.

PMID- 27696173
TI  - Implementation of a Novel Electronic Health Record-Embedded Physician Orders for
      Life-Sustaining Treatment System.
AB  - In April 2015, Oregon Health & Science University (OHSU) deployed a web-based,
      electronic medical record-embedded application created by third party vendor
      Vynca Inc. to allow real-time education, and completion of Physician Orders for
      Life Sustaining Treatment (POLST). Forms are automatically linked to the Epic
      SystemsTM electronic health record (EHR) patient header and submitted to a state
      Registry, improving efficiency, accuracy, and rapid access to and retrieval of
      these important medical orders. POLST Forms, implemented in Oregon in 1992, are
      standardized portable medical orders used to document patient treatment goals for
      end-of-life care. In 2009, Oregon developed the first POLST-only statewide
      registry with a legislative mandate requiring POLST form signers to register the
      form unless the patient opts out. The Registry offers 24/7 emergency access to
      POLST Forms for Emergency Medical Services, Emergency Departments, and Acute Care
      Units. Because POLST is intended for those nearing end of life, immediate access
      to these forms at the time of an emergency is critical. Delays in registering a
      POLST Form may result in unwanted treatment if the paper form is not immediately
      available. An electronic POLST Form completion system (ePOLST) was implemented to
      support direct Registry submission. Other benefits of the system include single
      sign-on, transmission of HL7 data for patient demographics and other relevant
      information, elimination of potential errors in form completion using
      internalized logic, built-in real-time video and text-based education materials
      for both patients and health care professionals, and mobile linkage for signature
      capture.

PMID- 27696174
TI  - A Provably Secure Aggregate Signature Scheme for Healthcare Wireless Sensor
      Networks.
AB  - Wireless sensor networks (WSNs) are being used in a wide range of applications
      for healthcare monitoring, like heart rate monitors and blood pressure monitors,
      which can minimize the need for healthcare professionals. In medical system,
      sensors on or in patients produce medical data which can be easily compromised by
      a vast of attacks. Although signature schemes can protect data authenticity and
      data integrity, when the number of users involved in the medical system becomes
      huge, the bandwidth and storage cost will rise sharply so that existing signature
      schemes are inapplicability for WSNs. In this paper, we propose an efficient
      aggregate signature scheme for healthcare WSNs according to an improved security
      model, which can combine multiple signatures into a single aggregate signature.
      The length of such an aggregate signature may be as long as that of an individual
      one, which can greatly decrease the bandwidth and storage cost for networks.

PMID- 27696175
TI  - m2-ABKS: Attribute-Based Multi-Keyword Search over Encrypted Personal Health
      Records in Multi-Owner Setting.
AB  - Online personal health record (PHR) is more inclined to shift data storage and
      search operations to cloud server so as to enjoy the elastic resources and lessen
      computational burden in cloud storage. As multiple patients' data is always
      stored in the cloud server simultaneously, it is a challenge to guarantee the
      confidentiality of PHR data and allow data users to search encrypted data in an
      efficient and privacy-preserving way. To this end, we design a secure
      cryptographic primitive called as attribute-based multi-keyword search over
      encrypted personal health records in multi-owner setting to support both fine
      grained access control and multi-keyword search via Ciphertext-Policy Attribute
      Based Encryption. Formal security analysis proves our scheme is selectively
      secure against chosen-keyword attack. As a further contribution, we conduct
      empirical experiments over real-world dataset to show its feasibility and
      practicality in a broad range of actual scenarios without incurring additional
      computational burden.

PMID- 27696176
TI  - Neural Basis of Visual Attentional Orienting in Childhood Autism Spectrum
      Disorders.
AB  - We examined spontaneous attention orienting to visual salience in stimuli without
      social significance using a modified Dot-Probe task during functional magnetic
      resonance imaging in high-functioning preadolescent children with Autism Spectrum
      Disorder (ASD) and age- and IQ-matched control children. While the magnitude of
      attentional bias (faster response to probes in the location of solid color patch)
      to visually salient stimuli was similar in the groups, activation differences in
      frontal and temporoparietal regions suggested hyper-sensitivity to visual
      salience or to sameness in ASD children. Further, activation in a subset of those
      regions was associated with symptoms of restricted and repetitive behavior. Thus,
      atypicalities in response to visual properties of stimuli may drive attentional
      orienting problems associated with ASD.

PMID- 27696177
TI  - Lexical Processing in Toddlers with ASD: Does Weak Central Coherence Play a Role?
AB  - This study investigated whether vocabulary delays in toddlers with autism
      spectrum disorders (ASD) can be explained by a cognitive style that prioritizes
      processing of detailed, local features of input over global contextual
      integration-as claimed by the weak central coherence (WCC) theory. Thirty
      toddlers with ASD and 30 younger, cognition-matched typical controls participated
      in a looking-while-listening task that assessed whether perceptual or semantic
      similarities among named images disrupted word recognition relative to a neutral
      condition. Overlap of perceptual features invited local processing whereas
      semantic overlap invited global processing. With the possible exception of a
      subset of toddlers who had very low vocabulary skills, these results provide no
      evidence that WCC is characteristic of lexical processing in toddlers with ASD.

PMID- 27696178
TI  - New Oral Anticoagulants and Their Reversal Agents.
AB  - OPINION STATEMENT: Direct oral anticoagulants (DOAC) are an attractive
      therapeutic option for anticoagulant treatment in the setting of venous
      thromboembolism or non-valvular atrial fibrillation. These drugs overall appear
      to have a lower risk of life-threatening hemorrhage than the vitamin K
      antagonists. In addition, they demonstrate more predictable and stable
      pharmacokinetics. Measurement of the degree of anticoagulation is desirable in
      patients with DOAC-associated hemorrhage, but commonly available coagulation
      assays show poor sensitivity for degree of DOAC effect. DOAC-specific tests are
      time consuming and not widely available. All coagulation tests should be
      interpreted considering the timing of last intake and renal function. When life
      threatening bleeding occurs, hemostasis should be restored as rapidly as
      possible. Non-specific prohemostatic drugs may have a role in DOAC reversal, and
      specific antidotes are at different stages of development. In this review, we
      provide a summary of DOAC characteristics and an overview of the different
      therapeutic options available for DOAC reversal.

PMID- 27696179
TI  - Long-Term Cognitive Improvement After Benfotiamine Administration in Patients
      with Alzheimer's Disease.
AB  - To date, we still lack disease-modifying therapies for Alzheimer's disease (AD).
      Here, we report that long-term administration of benfotiamine improved the
      cognitive ability of patients with AD. Five patients with mild to moderate AD
      received oral benfotiamine (300 mg daily) over 18 months. All patients were
      examined by positron emission tomography with Pittsburgh compound B (PiB-PET) and
      exhibited positive imaging with beta-amyloid deposition, and three received PiB
      PET imaging at follow-up. The five patients exhibited cognitive improvement as
      assayed by the Mini-Mental Status Examination (MMSE) with an average increase of
      3.2 points at month 18 of benfotiamine administration. The three patients who
      received follow-up PiB-PET had a 36.7% increase in the average standardized
      uptake value ratio in the brain compared with that in the first scan.
      Importantly, the MMSE scores of these three had an average increase of 3 points
      during the same period. Benfotiamine significantly improved the cognitive
      abilities of mild to moderate AD patients independently of brain amyloid
      accumulation. Our study provides new insight to the development of disease
      modifying therapy.

PMID- 27696180
TI  - Contamination by Norovirus and Adenovirus on Environmental Surfaces and in Hands
      of Conscripts in Two Finnish Garrisons.
AB  - This study investigated the presence of norovirus and adenovirus, especially
      enteric adenovirus, on the environmental surfaces (n = 481) and military
      conscripts' hands (n = 109) in two Finnish garrisons (A and B) in 2013 and 2014.
      A questionnaire study was conducted to reveal possible correlations between viral
      findings on the conscripts' hands and their acute gastroenteritis symptoms. In
      addition to the swab samples, 14 fecal samples were obtained for viral analysis.
      In total, norovirus was present in 9.0 % of the surface swabs in 2013, whereas
      enteric adenovirus was present in 0.0 % and non-enteric adenovirus in 9.4 %. In
      the same year, 2.6 % of the hand swabs contained norovirus, 2.6 % enteric
      adenovirus, and 40.3 % non-enteric adenovirus. Norovirus GI.6 was continually
      detected on the surfaces of garrison A, and identical virus was detected in some
      of the fecal samples. In garrison B, two slightly different norovirus GII.4
      strains were present on the surfaces. The questionnaires revealed no recent acute
      gastroenteritis cases in garrison A, but in garrison B, where the norovirus
      positive hand swabs were collected, 30.6 % of the conscripts reported of recent
      symptoms. In 2014, norovirus was rarely detected, but adenovirus was again
      frequently present, both on the surfaces and hands. Taken together, our results
      suggest that gastroenteritis outbreaks occurred in 2013, but not in 2014. Due to
      the low number of hand swabs positive for enteric viruses, no conclusions about
      associations between viral findings and gastroenteritis symptoms could be drawn.
      This study increased our understanding of the possible transmission of viruses
      via contaminated environment and hands.

PMID- 27696181
TI  - Comparison of excitation energy transfer in cyanobacterial photosystem I in
      solution and immobilized on conducting glass.
AB  - Excitation energy transfer in monomeric and trimeric forms of photosystem I (PSI)
      from the cyanobacterium Synechocystis sp. PCC 6803 in solution or immobilized on
      FTO conducting glass was compared using time-resolved fluorescence. Deposition of
      PSI on glass preserves bi-exponential excitation decay of ~4-7 and ~21-25 ps
      lifetimes characteristic of PSI in solution. The faster phase was assigned in
      part to photochemical quenching (charge separation) of excited bulk chlorophylls
      and in part to energy transfer from bulk to low-energy (red) chlorophylls. The
      slower phase was assigned to photochemical quenching of the excitation
      equilibrated over bulk and red chlorophylls. The main differences between
      dissolved and immobilized PSI (iPSI) are: (1) the average excitation decay in
      iPSI is about 11 ps, which is faster by a few ps than for PSI in solution due to
      significantly faster excitation quenching of bulk chlorophylls by charge
      separation (~10 ps instead of ~15 ps) accompanied by slightly weaker coupling of
      bulk and red chlorophylls; (2) the number of red chlorophylls in monomeric PSI
      increases twice-from 3 in solution to 6 after immobilization-as a result of
      interaction with neighboring monomers and conducting glass; despite the increased
      number of red chlorophylls, the excitation decay accelerates in iPSI; (3) the
      number of red chlorophylls in trimeric PSI is 4 (per monomer) and remains
      unchanged after immobilization; (4) in all the samples under study, the free
      energy gap between mean red (emission at ~710 nm) and mean bulk (emission at ~686
      nm) emitting states of chlorophylls was estimated at a similar level of 17-27
      meV. All these observations indicate that despite slight modifications, dried PSI
      complexes adsorbed on the FTO surface remain fully functional in terms of
      excitation energy transfer and primary charge separation that is particularly
      important in the view of photovoltaic applications of this photosystem.

PMID- 27696182
TI  - Mapping the Network of Neuropsychological Impairment in Children with Autism
      Spectrum Disorder: A Graph Theoretical Analysis.
AB  - Children with autism spectrum disorder (ASD) exhibit social-communicative
      impairments. Less is known about the neuropsychological profile of ASD, although
      cognitive and neuropsychological deficits are evident. We modelled
      neuropsychological function in 20 children with ASD and 20 sex, age and IQ
      matched typically-developing controls (ages 7-14) as a network of interacting
      parameters. Graph theoretical analysis was applied to identify critical
      topographic regions within this network. Two areas were significantly stronger
      hubs in typically-developing children, the ability to shift attention (p < 0.001)
      and overall executive function (p < 0.001). Planning/organization was a stronger
      hub in the cognitive networks of children with ASD (p = 0.001). We show that ASD
      is not only characterized by impairments in various neurocognitive domains, but
      also alterations in their interaction.

PMID- 27696183
TI  - Reduced Mimicry to Virtual Reality Avatars in Autism Spectrum Disorder.
AB  - Mimicry involves unconsciously copying the actions of others. Increasing evidence
      suggests that autistic people can copy the goal of an observed action but show
      differences in their mimicry. We investigated mimicry in autism spectrum disorder
      (ASD) within a two-dimensional virtual reality environment. Participants played
      an imitation game with a socially engaged avatar and socially disengaged avatar.
      Despite being told only to copy the goal of the observed action, autistic
      participants and matched neurotypical participants mimicked the kinematics of the
      avatars' movements. However, autistic participants mimicked less. Social
      engagement did not modulate mimicry in either group. The results demonstrate the
      feasibility of using virtual reality to induce mimicry and suggest mimicry
      differences in ASD may also occur when interacting with avatars.

PMID- 27696184
TI  - Perception of Life as Stressful, Not Biological Response to Stress, is Associated
      with Greater Social Disability in Adults with Autism Spectrum Disorder.
AB  - This study examined differences between adults with autism spectrum disorder
      (ASD; N = 40) and typical community volunteers (N = 25) on measures of stressful
      life events, perceived stress, and biological stress response (cardiovascular and
      cortisol reactivity) during a novel social stress task. Additional analyses
      examined the relationship between stress and social functioning as measured by
      the Social Adjustment Scale-II and the Waisman Activities of Daily Living scale.
      Results indicated that adults with ASD experienced significantly more stressful
      life events and perceived stress, and greater systolic blood pressure reactivity
      than typical community volunteers. Results also indicated that perceived stress
      and stressful life events were significantly associated with social disability.
      Interventions targeting stress management might improve social function in adults
      with ASD.

PMID- 27696185
TI  - Brief Report: Seeing the Man in the Moon: Do Children with Autism Perceive
      Pareidolic Faces? A Pilot Study.
AB  - Faces are one of the most socially significant visual stimuli encountered in the
      environment, whereas pareidolias are illusions of faces arising from ambiguous
      stimuli in the environment. Autism spectrum disorder (ASD) is characterised by
      deficits in response to social stimuli. We found that children with ASD (n = 60)
      identify significantly fewer pareidolic faces in a sequence of ambiguous stimuli
      than typically developing peers. The two groups did not differ in the number of
      objects identified, indicating that the children with ASD had a specific lack of
      attention to faces. Pareidolia have considerable potential as naturalistic and
      easy-to-create materials for the investigation of spontaneous attention to social
      stimuli in children with ASD.

PMID- 27696186
TI  - Anxiety Disorders in Williams Syndrome Contrasted with Intellectual Disability
      and the General Population: A Systematic Review and Meta-Analysis.
AB  - Individuals with specific genetic syndromes associated with intellectual
      disability (ID), such as Williams syndrome (WS), are at increased risk for
      developing anxiety disorders. A systematic literature review identified sixteen
      WS papers that could generate pooled prevalence estimates of anxiety disorders
      for WS. A meta-analysis compared these estimates with prevalence estimates for
      the heterogeneous ID population and the general population. Estimated rates of
      anxiety disorders in WS were high. WS individuals were four times more likely to
      experience anxiety than individuals with ID, and the risk was also heightened
      compared to the general population. The results provide further evidence of an
      unusual profile of high anxiety in WS.

PMID- 27696187
TI  - Reputation Management in Children on the Autism Spectrum.
AB  - Being able to manage reputation is an important social skill, but it is unclear
      whether autistic children can manage reputation. This study investigated whether
      33 autistic children matched to 33 typical children could implicitly or
      explicitly manage reputation. Further, we examined whether cognitive processes
      theory of mind, social motivation, inhibitory control and reciprocity-contribute
      to reputation management. Results showed that neither group implicitly managed
      reputation, and there was no group difference in explicit reputation management.
      Results suggested different mechanisms contribute to reputation management in
      these groups-social motivation in typical children and reciprocity in autistic
      children. Explicit reputation management is achievable for autistic children, and
      there are individual differences in its relationship to underlying cognitive
      processes.

PMID- 27696189
TI  - Hyperuricemia, Hypertension, and Chronic Kidney Disease: an Emerging Association.
AB  - Uric acid is a product of purine metabolism and has been linked to gout and
      kidney calculi. Chronic kidney disease (CKD) and hypertension (HTN) are two major
      public health problems, and both are associated with increased risk of
      cardiovascular events. Emerging evidence suggests a pathogenic role of
      hyperuricemia in the development of HTN and CKD, in addition to progression of
      CKD, by inducing renal inflammation, endothelial dysfunction, and activation of
      the renin-angiotensin system. In addition, several epidemiological studies have
      linked hyperuricemia with an increased risk of HTN and CKD. A few clinical trials
      have assessed the use of uric acid-lowering therapies such as allopurinol and
      febuxostat in the management of HTN and delaying progression of CKD. To date,
      most of these trials are short-term with a small sample size; however, their
      results are encouraging and provide a rationale for larger randomized controlled
      trials to establish the role of uric acid-lowering therapies in the management of
      HTN, in addition to prevention of CKD progression and cardiovascular events.

PMID- 27696190
TI  - Successful management of perioperative hemostasis in a patient with Glanzmann
      thrombasthenia who underwent a right total mastectomy.
AB  - Perioperative hemostatic management is a challenge in patients with Glanzmann
      thrombasthenia (GT). The standard means of preventing surgical bleeding in GT
      patients is platelet transfusion. However, GT patients often possess
      alloantibodies against GPIIb/IIIa and/or HLA, which cause resistance to platelet
      transfusion. HLA-matched platelet transfusion, plasmapheresis, or recombinant
      human-activated factor VII (rFVIIa) are alternative interventions in such cases.
      Monitoring of hemostasis is also critical in the management of GT patients who
      undergo surgery. Here, we report the case of a 56-year-old female GT patient with
      anti-HLA antibodies, who underwent a right total mastectomy without significant
      blood loss under HLA-matched platelet transfusion. Bleeding at the surgical site,
      which occurred on the 18th postoperative day, was successfully treated by
      immediate bolus administration of rFVIIa and subsequent HLA-matched platelet
      transfusion. The perioperative hemostatic state was monitored in combination with
      bleeding time, platelet aggregation assay, and flow cytometric analysis of
      GPIIb/IIIa expression. Although a flow cytometric analysis is not a functional
      assay, it enabled the estimation of transfused platelet counts, and helped to
      inform the decision regarding whether to perform the surgery. Thus, perioperative
      hemostasis was successfully managed in our GT patient by HLA-matched platelet
      transfusion, rFVIIa administration, and the close monitoring of hemostasis.

PMID- 27696191
TI  - ADAMTS13: more than a regulator of thrombosis.
AB  - ADAMTS13, a plasma reprolysin-like metalloprotease, proteolyzes von Willebrand
      factor (VWF). ADAMTS13 is primarily synthesized by hepatic stellate cells (HSCs),
      and mainly regulates thrombogenesis by cleaving VWF. Recent studies demonstrate
      that ADAMTS13 also plays a role in the down-regulation of inflammation,
      regulation angiogenesis, and degradation of extracellular matrix. The purpose of
      this review is to introduce the state of progress with respect to some of the
      theorized roles of ADAMTS13.

PMID- 27696192
TI  - Fulminant type I diabetes mellitus associated with nivolumab in a patient with
      relapsed classical Hodgkin lymphoma.
AB  - We report the case of a patient with relapsed classical Hodgkin lymphoma who
      developed fulminant type I diabetes mellitus as a severe adverse event of
      treatment with the anti-programmed cell death-1 (PD-1) antibody, nivolumab. On
      the first day of the sixth cycle, the blood glucose level was markedly elevated
      (375 mg/dL). Although neither ketoacidosis nor ketonuria was detected, the
      markedly acute onset of the hyperglycemia was consistent with the typical
      clinical course of fulminant type I diabetes mellitus, and this diagnosis was
      supported by clinical data. All autoantibodies associated with type I diabetes
      mellitus were negative. The endogenous insulin secretion ceased completely within
      2 weeks. After the blood glucose level was brought under control, nivolumab was
      resumed and continued without other major adverse events. Human leukocyte antigen
      (HLA) analysis revealed that the patient carried the HLA-B*4002 haplotype, a
      susceptibility allele for this type of diabetes mellitus. This case suggests that
      fulminant type I diabetes mellitus may be triggered by nivolumab in patients with
      a genetic background associated with the condition, warranting careful future
      consideration of this particular adverse event.

PMID- 27696193
TI  - Characterization, chemometric evaluation, and human health-related aspects of
      essential and toxic elements in Italian honey samples by inductively coupled
      plasma mass spectrometry.
AB  - Concentration values of 24 elements (Al, As, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, Ge,
      Hg, Mn, Mo, Pb, Sb, Se, Sn, Sr, Ti, Tl, U, V, and Zn) were determined in 72 honey
      samples produced in Italy by inductively coupled plasma mass spectrometry (ICP
      MS). Considering the recommended established heavy metal daily intakes for
      humans, in this perspective, an equilibrated and ordinary honey consumption
      should not be considered matter of concerns for human health, even if particular
      attention should be addressed if honey is consumed by children, due to different
      maximum daily heavy metal intakes. Chemometric analysis of the results obtained
      highlights heavy metal content differences in honey samples obtained from
      notoriously polluted zones, confirming then that honey can be considered a bio
      indicator of environmental pollution. Finally, Pearson coefficients highlighted
      correlations among element contents in honey samples.

PMID- 27696194
TI  - Advanced mortar coatings for cultural heritage protection. Durability towards
      prolonged UV and outdoor exposure.
AB  - In the present work, two kinds of hybrid polymeric-inorganic coatings containing
      TiO2 or SiO2 particles and prepared starting from two commercial resins
      (Alpha(r)SI30 and Bluesil(r)BP9710) were developed and applied to two kinds of
      mortars (an air-hardening calcic lime mortar [ALM] and a natural hydraulic lime
      mortar [HLM]) to achieve better performances in terms of water repellence and
      consequently damage resistance. The two pure commercial resins were also applied
      for comparison purposes. Properties of the coated materials and their performance
      were studied using different techniques such as contact angle measurements,
      capillary absorption test, mercury intrusion porosimetry, surface free energy,
      colorimetric measurements and water vapour permeability tests. Tests were also
      performed to determine the weathering effects on both the commercial and the
      hybrid coatings in order to study their durability. Thus, exposures to UV
      radiation, to UV radiation/condensed water cycles and to a real polluted
      atmospheric environment have been performed. The effectiveness of the hybrid SiO2
      based coating was demonstrated, especially in the case of the HLM mortar.

PMID- 27696196
TI  - Effect of landfill cover layer modification on methane oxidation.
AB  - Levels of methane (CH4) oxidation in materials used for landfill cover attained
      in the laboratory are not often replicated in the field due to effects from the
      surrounding environment. This study investigates the three dominant factors
      affecting CH4 oxidation in the cover layer, namely, the thickness of cover layer,
      the methanotroph spraying manner, and the osmotic coefficient of the cover
      material. Results show that improved CH4 emission performance of the cover layer
      can be realized if methanotroph are introduced, meaning that a thinner cover
      layer is required. The highest CH4 emission reduction can be realized by spraying
      methanotroph into the top, middle, and bottom layers of a 30-cm thick cover layer
      with an osmotic coefficient of 7.76 * 10-5 cm s-1. Comparing results on cover
      layer thickness, methane monooxygenase (MMO) activity was much lower with
      increasing thickness meaning that the thicker cover could reduce O2 availability,
      thus inhibiting MMO activity. This suggests that MMO may be responsible for
      differences in CH4 emission reduction and/or oxidation making the osmotic
      coefficient an important factor for cover layer material.

PMID- 27696195
TI  - Measurement of p-nitrophenyl acetate esterase activity (EA), total antioxidant
      capacity (TAC), total oxidant status (TOS) and acetylcholinesterase (AChE) in
      gills and digestive gland of Mytilus galloprovincialis exposed to binary mixtures
      of Pb, Cd and Cu.
AB  - The aims of the present work were (1) to evaluate oxidative stress biomarkers and
      AChE in two tissues of wild mussel (Mytilus galloprovincialis) of high
      biochemical activity and accumulation capacity (gills and digestive gland) and
      (2) to study the behaviour of these biomarkers in presence of heavy metals. For
      this, EA, TOS, TAC and AChE were measured in tissues of mussels exposed to binary
      combination of Pb, Cd and Cu. Mussels (n = 36) were exposed to one of the binary
      mixtures of Pb (1000 MUg L-1), Cd (100 MUg L-1) and Cu (100 MUg L-1) for 7 days,
      under controlled conditions. Gills and digestive gland were extracted and frozen
      at -80  degrees C until analysis. The automatic methods employed for the
      measurement of EA, TAC, TOS and AChE in M. galloprovincialis revealed higher
      levels of these biomarkers in digestive gland than gills. Study results suggest
      that gills would be the tissue of election for study oxidative stress markers,
      whereas digestive tissue should be selected for AChE measurements in case of
      evaluation of combined metal toxicity in mussels.

PMID- 27696197
TI  - In vivo protective role against water contamination with cerium via chronic
      administration of omega 3.
AB  - In the present study, adult, healthy male Wistar rats (120 +/- 10 g) were pre
      treated by intragastric administration of cerium chloride (CeCl3) 10 mg/kg (BW)
      each day during 60 days. Control animal were treated with omega 3, a
      polyunsaturated fatty acid (omega-3), by an intragastric administration at 10
      mg/kg of BW for 60 days. Our results showed that CeCl3-induced alterations in all
      tested oxidative stress markers. In fact, CeCl3-induced the increase the level of
      both the creatinine concentration and the expression of lactate dehydrogenase,
      alkaline phosphatase, and transaminase activities in serum. On the other hand,
      CeCl3 significantly increased the levels of lipid peroxidation in the renal and
      hepatic tissues. The capacity of CeCl3 to generate reactive oxygen species (ROS)
      could explain his ability to induce morphological alterations, such as
      centrilobular hemorrhage, hepatic necrosis, and vacuolization of the cytoplasm in
      hepatic tissues, and the atrophy of the glomerulus and dilatation of urinary
      space in renal tissues. However, omega 3, after gastric administration, reduced
      significantly the toxic effect caused by CeCl3 according to his high ability to
      scavenge ROS. The present study indicates that omega 3 is a significant compound
      with protective activity against intoxication with heavy metal, the cerium, and
      thus may be useful for chemoprevention.

PMID- 27696198
TI  - Thermodynamic study of seven micropollutants adsorption onto an activated carbon
      cloth: Van't Hoff method, calorimetry, and COSMO-RS simulations.
AB  - The thermodynamic of the adsorption of seven organic pollutants, namely
      benzotriazol, bisphenol A, caffeine, carbamazepine, diclofenac, ofloxacin, and
      pentachlorophenol, was studied on a microporous-activated carbon fabric. The
      isosteric adsorption quantities (Gibbs energy, enthalpy, and entropy variations)
      at high coverage ratio (around 1 mmol/g) have been determined from the adsorption
      isotherms at three temperatures (13, 25, and 40  degrees C). The adsorption heats
      at very low coverage (about 10-5 mmol/g) have been measured by flow micro
      calorimetry. The experimental adsorption energies were correlated to the
      adsorbate-adsorbent and the adsorbate-solvent interaction energies calculated by
      simulations using the COSMO-RS model. The main role of the van der Waals forces
      in the adsorption of the studied molecules was established. The bulkier the
      adsorbate is, the lower the adsorption Gibbs energy variation at high coverage
      deduced from the isotherms. The heterogeneity of the adsorption sites was brought
      out by calorimetric measurements. At high coverage, a physisorption phenomenon
      was observed. At very low coverage, high values of the adsorption heats were
      found (ranging from -58 to -110 kJ/mol), except for pentachlorophenol
      characterized by an athermal adsorption controlled by Pi-anions interactions.

PMID- 27696199
TI  - Mitigation of polar pesticides across a vegetative filter strip. A mesocosm
      study.
AB  - Vegetated filter strips (VFSs) are planted at the edge of agricultural fields to
      reduce pesticide run-off and its consequent potential toxicological effects on
      ecosystem biota; however, little attention has been paid to date to the
      attenuation of highly polar and ionisable pesticides such as phenoxyacid
      herbicides. This study assesses the effect of soil moisture, run-off flow and
      vegetation on the attenuation of MCPA, mecoprop, dicamba, dichlorprop,
      fenitrothion, atrazine and simazine by VFSs. Reactors measuring 5 m long by 0.1 m
      wide were each filled with 60 kg of soil from a real field VFS. VFSs planted with
      Phragmites australis and unvegetated control reactors were assessed. After a
      simulated rainfall event of 50 mm, two hydraulic loading rates (HLRs) were
      assessed (1 and 2 cm h-1). These results were compared to those from the same
      systems under water-saturated conditions. The results show that VFSs reduced the
      peak inlet concentration and pesticide mass by more than 90 % and that the
      presence of vegetation increased that attenuation (82-90 % without vegetation and
      90-93 % with vegetation, on average). The laboratory-scale study showed that such
      attenuation was due to sorption into the soil. The toxicity units of pesticides
      fell by more than 90 % in all cases, except under the water-saturated conditions,
      in which the decrease was lower (16 vs 54 %, for unvegetated and vegetated
      reactors). Therefore, the presence of vegetation was shown to be effective for
      reducing mass discharge of ionisable and highly polar pesticides into surface
      water bodies.

PMID- 27696200
TI  - Distribution and sources of sterol biomarkers in sediments collected from a
      tropical estuary in Northeast Brazil.
AB  - The Piaui-Real estuary is located along the southern coast of Sergipe state,
      Northeast Brazil. This estuary has great economic importance due to its physical,
      biological, and socioeconomic diversity, but it is subject to anthropogenic
      stress since the resident population in the town bordered by the estuarine system
      has grown in recent years. Thus, the possibility of sewage contamination
      originating from the approximately 450,000 inhabitants living within its drainage
      basin was investigated in this study. Sediment samples were collected from 15
      sampling stations along the estuarine system and extracted, followed by gas
      chromatography-mass spectrometry (GC-MS) analysis. Six sterols were quantified,
      indicating natural and anthropogenic sources. Coprostanol concentrations higher
      than 100 ng g-1 were observed in 47 % of the stations analyzed, indicating sewage
      contamination, which was confirmed by the diagnostic ratios calculated. Based on
      the Pearson correlation test, a significant correlation between coprostanol
      concentrations and total organic carbon content (TOC) was observed, indicating
      that sterols record the history of sewage inputs in this area. These results
      indicate that control of the organic inputs into the estuarine system is
      required. Graphical abstract Sterol markers were determined and sources assessed
      in surface sediments from Piaui-Real estuarine system.

PMID- 27696201
TI  - Isolated Cardiac Richter Syndrome: a Case Report.

PMID- 27696202
TI  - Expression of programmed cell death 1 and programmed cell death ligand 1 in
      extranodal NK/T-cell lymphoma, nasal type.
AB  - Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are new
      therapeutic targets in cancer immunotherapy. The aim of this study was to
      investigate the clinicopathological characteristics of PD-1 and PD-L1 expression
      in extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). We performed PD
      1 and PD-L1 immunostaining in 79 ENKTL biopsy samples and retrospectively
      analyzed medical records of all 79 patients from four tertiary referral
      hospitals. The expression of PD-1 and PD-L1 by tumor cells and/or infiltrating
      immune cells was evaluated. The expression rates of PD-L1 in tumor cells and
      infiltrating immune cells were 79.7 and 78.5 %, respectively, whereas PD-1 in
      tumor cells and infiltrating immune cells were 1.3 and 11.4 %. The PD-L1
      positivity in tumor cells and infiltrating immune cells was significantly
      associated with low international prognostic index (IPI) (P = 0.044 and 0.037,
      respectively). Patients with normal range of serum lactate dehydrogenase
      demonstrated a significantly higher PD-L1 positivity in tumor cells (P = 0.020).
      PD-L1-positive patients had a trend toward better overall survival compared with
      that in patients with PD-L1-negative in tumor cells and infiltrating immune cells
      (P = 0.498 and 0.435, respectively). The expression rate of PD-L1 was up to 79.7
      % in ENKTL, while PD-1 expression rate was very low. This is the first report
      describing the clinicopathological features and survival outcome according to
      expression of PD-1 and PD-L1 in ENKTL.

PMID- 27696204
TI  - Epileptic seizures and rhinocerebral mucormycosis during blinatumomab treatment
      in a patient with biphenotypic acute leukemia.

PMID- 27696203
TI  - All-trans retinoic acid as adjunct to intensive treatment in younger adult
      patients with acute myeloid leukemia: results of the randomized AMLSG 07-04
      study.
AB  - The aim of this clinical trial was to evaluate the impact of all-trans retinoic
      acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as
      biomarker for ATRA therapy in younger adult patients (18-60 years) with acute
      myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with
      or without open-label ATRA (45 mg/m2, days 6-8; 15 mg/m2, days 9-21). Two cycles
      of induction therapy were followed by risk-adapted consolidation with high-dose
      cytarabine or allogeneic hematopoietic cell transplantation. Due to the open
      label character of the study, analysis was performed on an intention-to-treat
      (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were
      randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median
      follow-up for survival was 5.2 years. ITT analyses revealed no difference between
      ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML
      with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p
      = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS
      in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03).
      Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in
      ATRA for genetic low-risk patients according to ELN recommendations. The clinical
      trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321
      95).

PMID- 27696205
TI  - Gastric plexiform schwannoma in association with neurofibromatosis type 2.
AB  - : Plexiform schwannoma (PS) is an uncommon variant of schwannoma characterized by
      a multinodular (plexiform) growth pattern. It comprises up to 5 % of all
      schwannomas. The association between PS and neurofibromatosis type 1 or type 2
      (NF1/NF2) is only rarely reported. Most cases of PS occur in the skin and
      subcutaneous soft tissue, with only a few reports of digestive tract involvement.
      We describe an 18-year-old male with NF2 who had bilateral vestibular schwannomas
      and multiple cutaneous PSs, and a 3-year history of abdominal pain. The patient
      ultimately underwent a distal gastrectomy for a partially obstructing submucosal
      antral mass, associated with an overlying ulcer. Histopathologic examination
      showed the mass to be a PS. The patient is alive and well, without symptoms, 12
      months postoperatively. A review of the English language medical literature
      yielded only ten examples of PS arising in the digestive tract. Our patient is
      the first to be reported to have a gastric PS, and only the second patient to be
      reported with a digestive tract PS to have NF2, and the only patient reported to
      have both digestive tract and cutaneous PSs. Despite its rare occurrence with
      NF2, the finding of PS at any site should stimulate an examination for other
      manifestations of this disorder. CLINICAL TRIAL REGISTRATION: None.

PMID- 27696206
TI  - Molecular Recognition of Azelaic Acid and Related Molecules with DNA Polymerase I
      Investigated by Molecular Modeling Calculations.
AB  - Molecular recognition has central role on the development of rational drug
      design. Binding affinity and interactions are two key components which aid to
      understand the molecular recognition in drug-receptor complex and crucial for
      structure-based drug design in medicinal chemistry. Herein, we report the binding
      affinity and the nonbonding interactions of azelaic acid and related compounds
      with the receptor DNA polymerase I (2KFN). Quantum mechanical calculation was
      employed to optimize the modified drugs using B3LYP/6-31G(d,p) level of theory.
      Charge distribution, dipole moment and thermodynamic properties such as
      electronic energy, enthalpy and free energy of these optimized drugs are also
      explored to evaluate how modifications impact the drug properties. Molecular
      docking calculation was performed to evaluate the binding affinity and nonbonding
      interactions between designed molecules and the receptor protein. We notice that
      all modified drugs are thermodynamically more stable and some of them are more
      chemically reactive than the unmodified drug. Promise in enhancing hydrogen bonds
      is found in case of fluorine-directed modifications as well as in the addition of
      trifluoroacetyl group. Fluorine participates in forming fluorine bonds and also
      stimulates alkyl, pi-alkyl interactions in some drugs. Designed drugs revealed
      increased binding affinity toward 2KFN. A1, A2 and A3 showed binding affinities
      of -8.7, -8.6 and -7.9 kcal/mol, respectively against 2KFN compared to the
      binding affinity -6.7 kcal/mol of the parent drug. Significant interactions
      observed between the drugs and Thr358 and Asp355 residues of 2KFN. Moreover,
      designed drugs demonstrated improved pharmacokinetic properties. This study
      disclosed that 9-octadecenoic acid and drugs containing trifluoroacetyl and
      trifluoromethyl groups are the best 2KFN inhibitors. Overall, these results can
      be useful for the design of new potential candidates against DNA polymerase I.

PMID- 27696207
TI  - Bioactivity of Marine Streptomyces sp. VITJS4: Interactions of Cytotoxic
      Phthalate Derivatives with Human Topoisomerase II alpha: An In Silico Molecular
      Docking Analysis.
AB  - Despite clinical advances in antimicrobial and anticancer therapy, there is an
      urge for the search of new bioactive compounds. In the present study, previously
      isolated Streptomyces sp. VITJS4 strain (NCIM No. 5574) (ACC No: JQ234978.1)
      crude extract tested for antibacterial activity showed a broad spectrum at the
      concentration of 20 mg/mL against pathogens. The antioxidant potential tested at
      0.5 mg/mL concentration exhibited reducing power activity with a maximum of 90 %
      inhibition. The anticancer property by MTT assay on HeLa and HepG2 cells showed
      cytotoxic effect with IC50 of 50 ug/mL each. The DNA fragmentation pattern
      observed in both HeLa and HepG2 cell indicated laddering pattern at 40 ug/mL
      concentration. GC-MS analysis revealed that the significant peak corresponding at
      m/z 149 (M+) was identified as phthalate derivatives. The extract was further
      separated by HPLC with their retention times (t r) at 6.294 min. The above
      obtained results were also supported by molecular docking studies which provide
      an insight into ligand binding to the active site of the receptor. The in silico
      docking studies revealed better binding affinity with a binding energy of -5.87
      kJ mol-1 of the ligand toward topoisomerase II alpha.

PMID- 27696208
TI  - Structure-Based Drug Designing and Simulation Studies for Finding Novel
      Inhibitors of Heat Shock Protein (HSP70) as Suppressors for Psoriasis.
AB  - Psoriasis is a chronic immune-mediated inflammatory skin disorder. Heat shock
      proteins (HSPs) have been witnessed as a potential drug target for inhibition of
      psoriatic cell differentiation. The expression level of HSP is increased when the
      cells get exposed to elevated temperature, oxidative stress and nutritional
      deficiencies and thus plays major role in psoriatic progression pathway.
      Immunoreactivity intensity distribution index scores for HSP70 expression is
      significantly higher in psoriatic patients compared to normal. In the present
      work, the 3D structure of human Hsp70 has been taken. Inhibition of HSP70 can
      control the severity of psoriasis up to many folds; thus, virtual screening was
      performed against lead-like, drug-like and some natural product of ZINC database.
      The screened ligands were further introduced to ADMET prediction and simulations
      to see the drug proficiency and likeness property. The molecular dynamic of
      system was found stable during simulation trajectory and not much of significant
      changes occurred in the conformation of the protein-ligand complex. Thus, present
      study in all probability might prove useful for future design of new derivatives
      with higher potency and specificity.

PMID- 27696209
TI  - Impact of Delta Hemoglobin on Provider Transfusion Practices and Post-operative
      Morbidity Among Patients Undergoing Liver and Pancreatic Surgery.
AB  - BACKGROUND: Delta hemoglobin (DeltaHb) is defined as the difference between the
      preoperative Hb and the lowest post-operative Hb level. We sought to define the
      impact of DeltaHb relative to nadir Hb levels on the likelihood of transfusion,
      as well as characterize the impact of DeltaHb and nadir Hb on morbidity among a
      large cohort of patients undergoing complex hepatopancreatobiliary (HPB) surgery.
      METHODS: Patients who underwent pancreatic or hepatic resection between January
      1, 2009 and June 30, 2015 at Johns Hopkins Hospital were identified. Data on the
      perioperative DeltaHb, nadir Hb, as well as blood utilization were obtained and
      analyzed. Multivariable logistic regression models were used to identify the
      factors associated with DeltaHb and the impact of DeltaHb on perioperative
      morbidity. A Bayesian model was used to evaluate the correlation of DeltaHb and
      nadir Hb with the likelihood of transfusion, as well as the impact on morbidity.
      RESULTS: A total of 4363 patients who underwent hepatobiliary (n = 2200, 50.4 %)
      or pancreatic (n = 2163, 49.6 %) surgery were identified. More than one quarter
      of patients received at least one unit of packed red blood cells (PRBC) (n =
      1187, 27.2 %). The median nadir Hb was 9.2 (IQR 7.9-10.5) g/dL resulting in an
      average DeltaHb of 3.4 mg/dL (IQR 2.2-4.7) corresponding to 26.3 %. Both DeltaHb
      and nadir Hb strongly influenced provider behavior with regards to use of
      transfusion. Among patients with the same nadir Hb, DeltaHb was strongly
      associated with use of transfusion; among patients who had a nadir Hb <=6 g/dL,
      the use of transfusion was only 17.9 % when the DeltaHb = 10 % versus 49.1 and
      80.9 % when the DeltaHb was 30 or 50 %, respectively. Perioperative complications
      occurred in 584 patients (13.4 %) and were more common among patients with a
      higher value of DeltaHb, as well as patients who received PRBC (both P < 0.001).
      CONCLUSIONS: The combination of the Hb trigger with DeltaHb was associated with
      transfusion practices among providers. Larger DeltaHb values, as well as receipt
      of transfusion, were strongly associated with risk of perioperative complication
      following HPB surgery.

PMID- 27696210
TI  - Investigation of noise sources for digital radiography systems.
AB  - The performance of digital radiography systems can be evaluated in terms of
      spatial resolution and noise. Noise plays an important role in the achievable
      image quality for detecting small and low-contrast structures in digital images
      created by these systems. Our aim in this study was to investigate the noise
      sources both in the spatial and frequency domain for three digital radiography
      systems, one digital fluoroscopy system, and one digital mammography system, and
      to obtain information about the effective operating dose range of these
      detectors. Noise evaluation in the spatial domain was done with the relative
      standard deviation-detector air kerma relationship evaluation method. The
      characterization of the noise in the spatial domain gives information about the
      types of noise, but does not give information about the noise power distribution
      in frequency space. Therefore, noise evaluation in the frequency domain was
      carried out by noise power spectrum measurement. The observed dominant noise
      component at lower detector doses was electronic noise for the digital
      mammography system, whereas structured noise was observed to make up nearly half
      of the total noise at higher detector doses for one of the digital radiography
      systems. The structured noise component was increased by use of a grid in these
      systems, independent of the grid ratio and grid frequency, but this increase was
      lower for higher grid frequencies. Furthermore, the structured noise coefficient
      was decreased with gain and offset calibrations. The five systems which we
      evaluated behaved as a quantum noise limited for clinically used detector doses.

PMID- 27696211
TI  - The Myocyte-Damaging Effects of the BCR-ABL1-Targeted Tyrosine Kinase Inhibitors
      Increase with Potency and Decrease with Specificity.
AB  - Five clinically approved BCR-ABL1-targeted tyrosine kinase inhibitors (bosutinib,
      dasatinib, imatinib, nilotinib, and ponatinib) used for treating chronic
      myelogenous leukemia have been studied in a neonatal rat myocyte model for their
      relative ability to induce myocyte damage. This was done in order to determine if
      kinase inhibitor-induced myocyte damage was a consequence of inhibiting ABL1 (on
      target effects), or due to a lack of kinase selectivity (off-target effects)
      since previous studies have come up with conflicting conclusions about whether
      imatinib-induced cardiotoxicity results directly from inhibition of ABL1. The
      most specific and least potent inhibitors, imatinib and nilotinib, induced the
      least myocyte damage, while the least specific and most potent inhibitors,
      ponatinib and dasatinib, induced the most damage. Inhibitor-induced myocyte
      damage also correlated with clinically observed cardiovascular toxicity. Growth
      inhibition of the erythroleukemic K562 human cell line with a constitutively
      active BCR-ABL1 kinase was negatively correlated with inhibitor-induced myocyte
      damage, which suggests that inhibition of ABL1 causes myocyte damage. Myocyte
      damage was also negatively correlated with inhibitor dissociation binding
      constants and with inhibition of enzymatic ABL1 kinase activity. Myocyte damage
      was also positively correlated with two measures of inhibitor selectivity, which
      suggests that a lack of inhibitor selectivity is responsible for myocyte damage.
      In conclusion, myocyte damage, and thus the cardiovascular toxicity of the BCR
      ABL1-targeted tyrosine kinase inhibitors, is due to direct inhibition of ABL1
      and/or their lack of inhibitor selectivity.

PMID- 27696212
TI  - Neonatal gastrointestinal perforation in Japan: a nationwide survey.
AB  - PURPOSE: The purpose of this study is to identify the current clinical features
      of neonatal gastrointestinal perforation in Japan. METHODS: A questionnaire about
      cases of neonatal gastrointestinal perforation treated in recent 5 years was sent
      to participating institutions of the Japanese Society of Pediatric Surgeons
      (JSPS). RESULTS: Five hundred and thirty-six neonates with gastrointestinal
      perforation were treated. They consisted of 42 patients with gastric
      rupture/perforation (GR), 33 patients with intestinal atresia/stenosis (IA), 3
      patients with malrotation (ML), 118 patients with necrotizing enterocolitis
      (NEC), 160 patients with focal intestinal perforation (FIP), 46 patients with
      meconium-related ileus (MRI), 77 patients with meconium peritonitis (MP), and 57
      patients with other conditions. The total mortality rate was 20.5 %. The
      mortality rates of the patients with GR, IA, ML, NEC, FIP, MRI, and MP were 9.5,
      9.1, 0, 33.1, 20.6, 28.2, and 9.1 %, respectively. In 263 cases involving
      extremely low-birth-weight neonates (ELBW), 108 died (mortality rate 41.1 %). The
      mortality rates for ELBW with GR, NEC, FIP, MRI, MP, and other conditions were
      27.3 % (3/11), 58.5 % (48/82), 21.6 % (24/111), 70.6 % (24/34), 57.1 % (4/7), and
      27.8 % (5/18), respectively. CONCLUSIONS: The mortality rates for ELBW decreased
      from 62.8 % in the previous survey to 41.1 % by the time of this survey.

PMID- 27696213
TI  - Primary spontaneous mesencephalic hemorrhage.

PMID- 27696214
TI  - Socioeconomic status is associated with urinary diversion utilization after
      radical cystectomy for bladder cancer.
AB  - PURPOSE: To assess socioeconomic disparities in urinary diversion utilization in
      a contemporary American cohort. METHODS: In the National Cancer Database, we
      identified 4538 patients who underwent cystectomy with urinary diversion for
      clinical T1-2N0M0 bladder cancer from 2010 to 2013. Multivariable logistic
      regression was used to identify predictors of urinary diversion type: ileal
      conduit (IC), continent cutaneous reservoir (CCR), or orthotopic neobladder (ON).
      Covariates included age, gender, race, income, Charlson score, clinical T stage,
      hospital cystectomy volume, teaching status, and surgical approach. Subgroup
      analysis by hospital volume (low, intermediate, or high) and teaching status
      (academic or non-academic) was performed to ascertain the impact of
      regionalization on urinary diversion use. RESULTS: The final cohort included 4066
      (89.6 %) patients with IC, 292 (6.4 %) with CCR, and 180 (4.0 %) with ON. On
      multivariable analysis, younger age (p < .01), higher income (p < .01), and high
      cystectomy volume predicted increased use of CCR and ON. Female gender predicted
      increased use of CCR versus IC (p < .01), and academic hospital status predicted
      increased use of ON versus IC (p = .04). On subgroup analysis, after further
      adjustment for hospital volume and teaching status, higher income remained an
      independent predictor of ON use. CONCLUSIONS: Despite regionalization of care,
      higher income patients are more likely to receive complex urinary diversions
      after radical cystectomy. Other related socioeconomic factors, especially patient
      education, may influence this practice pattern.

PMID- 27696215
TI  - Employment of Near Full-Length Ribosome Gene TA-Cloning and Primer-Blast to
      Detect Multiple Species in a Natural Complex Microbial Community Using Species
      Specific Primers Designed with Their Genome Sequences.
AB  - It remains an unsolved problem to quantify a natural microbial community by
      rapidly and conveniently measuring multiple species with functional significance.
      Most widely used high throughput next-generation sequencing methods can only
      generate information mainly for genus-level taxonomic identification and
      quantification, and detection of multiple species in a complex microbial
      community is still heavily dependent on approaches based on near full-length
      ribosome RNA gene or genome sequence information. In this study, we used near
      full-length rRNA gene library sequencing plus Primer-Blast to design species
      specific primers based on whole microbial genome sequences. The primers were
      intended to be specific at the species level within relevant microbial
      communities, i.e., a defined genomics background. The primers were tested with
      samples collected from the Daqu (also called fermentation starters) and pit mud
      of a traditional Chinese liquor production plant. Sixteen pairs of primers were
      found to be suitable for identification of individual species. Among them, seven
      pairs were chosen to measure the abundance of microbial species through
      quantitative PCR. The combination of near full-length ribosome RNA gene library
      sequencing and Primer-Blast may represent a broadly useful protocol to quantify
      multiple species in complex microbial population samples with species-specific
      primers.

PMID- 27696216
TI  - Correlates of Condom Use and Procedure Knowledge Among Men Accessing Voluntary
      Medical Male Circumcision in Malawi.
AB  - PURPOSE: This study examined correlates of condom use (CU) and voluntary medical
      male circumcision (VMMC) knowledge among men accessing VMMC services in Malawi.
      METHODS: Two hundred sixty-nine men ages 16 or older accessing VMMC were
      recruited at service sites. Bivariate and multivariate logistic regressions were
      used to determine associations, and the relative odds of CU at last sex with VMMC
      knowledge. Correlates included the following: education, age, location, religion,
      marital status, ever tested for HIV, having casual/concurrent sexual partners,
      and alcohol use before sex. RESULTS: The multivariate analysis revealed CU was
      associated with having a casual/concurrent partner in the previous 3 months and
      negatively associated with being age 27 or older and single, with participants
      who had casual/concurrent partners being more likely to use condoms than
      counterparts who did not have casual/concurrent partners, and those who were over
      age 27 and single being less likely to do so. VMMC knowledge was associated with
      education and location, with men with higher education and living in urban areas
      more likely to know that VMMC partially protects against HIV. CONCLUSION: Results
      highlight the need to ensure information about VMMC is appropriate for rural men
      with lower education. Further research is needed to understand the risk profile
      of men accessing VMMC and the reasons why men who do not know VMMC partially
      protects against HIV are seeking the service.

PMID- 27696217
TI  - Decoding the Structure of Abuse Potential for New Psychoactive Substances:
      Structure-Activity Relationships for Abuse-Related Effects of 4-Substituted
      Methcathinone Analogs.
AB  - Many cathinone analogs act as substrates or inhibitors at dopamine,
      norepinephrine, and serotonin transporters (DAT, NET, SERT, respectively). Drug
      selectivity at DAT vs. SERT is a key determinant of abuse potential for monoamine
      transporter substrates and inhibitors, such that potency at DAT > SERT is
      associated with high abuse potential, whereas potency at DAT < SERT is associated
      with low abuse potential. Quantitative structure-activity relationship (QSAR)
      studies with a series of 4-substituted methcathinone analogs identified volume of
      the 4-position substituent on the methcathinone phenyl ring as one structural
      determinant of both DAT vs. SERT selectivity and abuse-related behavioral effects
      in an intracranial self-stimulation procedure in rats. Subsequent modeling
      studies implicated specific amino acids in DAT and SERT that might interact with
      4-substituent volume to determine effects produced by this series of cathinone
      analogs. These studies illustrate use of QSAR analysis to investigate
      pharmacology of cathinones and function of monoamine transporters.

PMID- 27696218
TI  - Analgesic Drug Prescription Patterns on Five International Paediatric Wards.
AB  - AIM: Analgesic and anti-inflammatory drugs are frequently prescribed in
      paediatrics. Prescribing and dosing patterns in hospitalised children are not
      well known. This study explores analgesic drug utilisation on five paediatric
      wards and discusses its findings in comparison with World Health Organization
      (WHO) guidelines. METHOD: A sub-analysis of a prospective, multicentre,
      observational cohort study was undertaken. Prescription data of children aged up
      to <=18 years were collected between October 2008 and December 2009 on paediatric
      general medical wards in five hospitals in Australia, Germany, the United Kingdom
      (UK), Hong Kong (HK) and Malaysia. Analgesic drug prescriptions were analysed for
      prescribing patterns in terms of dosing, frequency and route of administration.
      Dosing data were compared with local recommendations and WHO guidelines for
      children. RESULTS: In the study cohort, 56.8 % (726/1278) of paediatric patients
      received at least one analgesic drug prescription (1227 prescriptions). The
      median age of patients with analgesics was 2.2 years [interquartile range (IQR)
      0.8-7.3], and the median number of prescriptions per patient was one (IQR 1-2).
      The most commonly prescribed drugs were oral paracetamol (45.9 %, 563/1227) and
      oral ibuprofen (19.9 %, 244/1227). Daily doses of paracetamol ranged from 30
      mg/kg/day in Germany to 67-68 mg/kg/day in the UK and HK (p < 0.05). For
      ibuprofen, single doses ranged from 5-6 mg/kg in HK and the UK to 10 mg/kg in
      Germany and Australia (p < 0.001). Opioid use prevalence was statistically
      different between the centres and ranged from 0 to 17.6 % (p < 0.001).
      CONCLUSION: This study provides a comprehensive overview of analgesic drug use of
      hospitalised children. Similar to primary care data, paracetamol is the most
      commonly used analgesic. As recommended by WHO guidelines, oral medication was
      favoured and opioids used in addition to paracetamol and ibuprofen. Overall drug
      utilisation was in line with local recommendations and WHO guidelines.
      Differences in use of paracetamol and ibuprofen among countries were seen,
      indicating that safety concerns are perceived differently. More large-scale
      safety studies are needed.

PMID- 27696219
TI  - A mixed methods study of ruminant brucellosis in central-eastern Tunisia.
AB  - In this study, we conducted an investigation to determine the true prevalence of
      bovine and ovine brucellosis in central-eastern Tunisia. A total of 1134
      veterinary samples taken from 130 ruminant herds were screened for brucellosis
      using IS711-based real-time PCR assay. Sera collected from the ruminants were
      tested using the Rose Bengal test and indirect enzyme-linked immunosorbent assay.
      Based on serological and molecular results, the true adjusted animal population
      level prevalence was 23.5 % in cattle, against 13.5 % in sheep. In addition, the
      true adjusted herd level prevalence of brucellosis was 55.6 % in cattle and 21.8
      % in sheep. A statistically significant association was found between vaginal and
      milk shedding for ruminants. In addition, our results showed that Brucella
      abortus could be responsible for bovine and ovine brucellosis. Multivariable
      logistic regression analysis at the animal population level indicated that age
      and origin variables were important risk factors for cattle. However, age and
      abortion variables were found to be associated with ovine brucellosis. At the
      herd level, risk factors for Brucella positivity were as follows: abortion and
      herd composition for cattle against herd composition, mortality rates, and
      hygiene for sheep. Animal hygiene, food quality, and sanitary practices on the
      farm should be applied as strategies to control brucellosis in herds.

PMID- 27696220
TI  - Population Pharmacokinetics of Necitumumab in Cancer Patients.
AB  - Necitumumab is a second-generation, recombinant, human immunoglobulin G1,
      epidermal growth factor (EGFR) receptor antibody that specifically blocks the
      ligand binding site of EGFR. Necitumumab potentially acts by blocking ligand
      epidermal growth factor (EGF) binding-mediated activation of the EGFR signaling
      pathway, inhibiting tumor growth, angiogenesis, and anti-apoptotic mechanisms.
      Necitumumab inhibited the interaction of EGF and EGFR with a concentration that
      inhibits binding by 50 % of approximately 0.9 nM (0.13 mg/L) and demonstrated
      antitumor activity during in vivo experiments associated with trough plasma
      concentrations of approximately 40 mg/L. This work describes the population
      pharmacokinetics of necitumumab in cancer patients when administered with or
      without concomitant chemotherapy and evaluates patient characteristics that may
      guide dosing. Nonlinear mixed-effects modeling of serum concentration data across
      five clinical studies (phases I-III) indicated that necitumumab exhibited target
      mediated drug disposition, commonly observed with monoclonal antibodies, and that
      pharmacokinetics were expected to be linear in the studied dose ranges when
      administered as repeated infusions. No age, sex, race, or concomitant medication
      factors were found influential, while weight was a statistically significant
      factor for both distribution and elimination. Simulations from the final model
      indicated that only a limited reduction in patient drug exposure variability
      would be achieved by weight- or body surface area-based dosing. Necitumumab
      effective half-life was estimated to approximately 2 weeks, and steady state was
      achieved within three to four cycles of treatment. The phase III dosing schedule
      of 800 mg dosed on days 1 and 8 of a 21-day schedule resulted in serum
      concentrations that exceeded the 40-mg/L threshold indicated by preclinical
      experiments.

PMID- 27696221
TI  - A Review of Insulin Degludec/Insulin Aspart: Pharmacokinetic and Pharmacodynamic
      Properties and Their Implications in Clinical Use.
AB  - Insulin degludec/insulin aspart (IDegAsp; 70 % IDeg and 30 % IAsp) is a soluble
      combination of two individual insulin analogues in one product, designed to
      provide mealtime glycaemic control due to the IAsp component and basal glucose
      lowering effect from the IDeg component. The pharmacokinetic and pharmacodynamic
      characteristics of IDegAsp have been investigated in a series of clinical
      pharmacology studies with generally comparable designs, methodologies and patient
      inclusion/exclusion criteria. The glucose-lowering effect profile of IDegAsp
      during once-daily dosing at steady state shows distinct and clearly separated
      action from the prandial and basal components of IDegAsp. The IAsp component
      provides rapid onset and peak glucose-lowering effect followed by a flat glucose
      lowering effect lasting beyond 30 h due to IDeg. During twice-daily dosing, the
      distinct peak effect and the flat basal effect are retained following each dose.
      The pharmacological properties of IDegAsp are maintained in the elderly,
      children, adolescents, Japanese patients and those with hepatic or renal
      impairment. The potential clinical benefits associated with the pharmacological
      properties of IDegAsp have been verified in phase III clinical trials comparing
      IDegAsp with three other currently available treatment options: premixed insulin,
      basal-bolus regimens and basal-only therapy. IDegAsp shows favourable clinical
      benefits compared with biphasic insulin aspart 30 and is a viable alternative to
      basal-bolus and basal-only therapy. This review presents the results from
      clinical pharmacology studies conducted with IDegAsp to date, and extrapolates
      these results to clinical use of IDegAsp in the context of findings from the
      IDegAsp clinical therapeutic studies.

PMID- 27696222
TI  - Gene Expression Profiling Stratifies IDH1-Mutant Glioma with Distinct Prognoses.
AB  - Isocitrate dehydrogenase (IDH)1 mutation is one of the most important genetic
      aberrations in glioma. Even several genetic events have refined its prognostic
      value, the genome-wide expression alteration has not been systematically
      profiled. In this work, RNA-seq expression data from 310 patients in the Chinese
      Glioma Genome Atlas database were included as training set, while another 297
      patients with microarray data were used as internal validation set. An
      independent cohort of GSE16011 (n = 205) constituted an external validation set.
      Approximately one fifth of the genes were differentially expressed in LGG
      according to IDH1 mutation status, yielding distinct gene expression profiles. A
      six-gene risk signature was established for IDH1-mutant LGG to distinguish low-
      from high-risk cases, which had distinct prognoses. The six-gene signature was an
      independent prognostic factor for IDH1-mutant LGG and had superior predictive
      value as compared to traditional clinicopathologic factors. Moreover, we depicted
      the differential expression pattern in GBM attributing to various IDH1 status,
      which was similar to that of LGG. It suggested that the effect of IDH1 mutation
      is conserved across histological classifications. The six-gene signature had
      equal prognostic value for IDH1-mutant GBM. By combining glioma grade, IDH1
      status, and the six-gene signature, all glioma patients could be classified into
      six subgroups. These six subgroups could be further summarized into three sets
      with distinct prognosis. Taken together, a gene expression profile associated
      with IDH1 status was identified in LGG and GBM; a risk signature based on six
      genes was developed with equal prognostic value for IDH1-mutant LGG and GBM. When
      combined with clinicopathologic factors, the six-gene signature is a tool that
      enables precise risk stratification and can improve clinical management.

PMID- 27696224
TI  - Cyanidation of Mercury-Contaminated Tailings: Potential Health Effects and
      Environmental Justice.
AB  - There is a variety of health and environmental issues associated with artisanal
      and small-scale gold mining (ASGM), which includes concerns regarding mercury
      pollution. In many countries, intervention programs and policies emphasized the
      importance of reducing mercury use by focusing on viable alternative methods to
      amalgamation that may include a transition to cyanidation. ASGM communities that
      now employ a combination of both methods may be increasing health and
      environmental risks by using mercury-contaminated tailings in the cyanidation
      process. This review provides a current overview of mercury and cyanide use in
      ASGM including the dangers of centralized processing centers that lack best
      practices. The combination of amalgamation and cyanidation has the potential to
      adversely affect many ASGM communities around the world and necessitates
      additional investigations to determine environmental and health impacts.

PMID- 27696223
TI  - Nrf2-a Promising Therapeutic Target for Defensing Against Oxidative Stress in
      Stroke.
AB  - Stroke is one of the leading causes of death and disability in the world.
      Oxidative stress, which refers to an excessive generation of reactive oxygen
      species (ROS), plays a key role in the pathological process of stroke. Excessive
      ROS production contributes to brain ischemia/reperfusion injury through many
      mechanisms including BBB disruption, inflammation, apoptosis, and cellular
      necrosis. Nuclear factor-E2-related factor 2 (Nrf2) is one of the critical
      regulators of endogenous antioxidant defense, which promote the transcription of
      a wide variety of antioxidant genes. Emerging evidence has demonstrated that
      activation of Nrf2 and its target genes may protect the brain against
      ischemia/reperfusion injury, and therapies aimed at increasing Nrf2 activity
      appear to be beneficial to alleviate brain injury in stroke through the
      suppression of oxidative stress. The main purpose of this review is to discuss
      the current evidence for the role of Nrf2 in stroke and the potential
      interventions to enhance Nrf2 activation to attenuate stroke-induced injury.

PMID- 27696226
TI  - FAT4 hypermethylation and grade dependent downregulation in gastric
      adenocarcinoma.
AB  - Gastric cancer is one of the major causes of death due to cancer in the world. It
      is a multi-factorial disease with epigenetic factors being also involved in its
      development. FAT4 is a tumor suppressor gene exerting an important role in cell
      adhesion. This study aimed at analyzing FAT4 expression and promoter methylation
      in gastric cancer. FAT4 expression was studied in 30 tumoral tissues and their
      non-tumoral counterparts using Taqman real time PCR method. Promoter methylation
      was assessed using bisulfite conversion method followed by sequencing. Tumor
      tissues showed reduced FAT4 expression (P = 0.04). FAT4 downregulation was
      associated with tumor grade, with higher repression at advanced grades.
      Significant increase of promoter methylation was observed in tumoral tissues.
      Reduced expression of FAT4 and increased methylation of its promoter may be one
      of the effective processes in turning a healthy stomach tissue into a tumor
      tissue.

PMID- 27696227
TI  - Replication of Toxoplasma gondii in chicken erythrocytes and thrombocytes
      compared to macrophages.
AB  - Toxoplasma (T.) gondii is able to infect various cell types in different hosts.
      The replication of this parasite within different peripheral mononuclear blood
      cell populations in chicken has not yet been fully understood. Aim of the present
      study was to investigate the impact of chicken erythrocytes and thrombocytes as
      potential host cells for T. gondii. Cultures of primary avian erythrocytes and
      thrombocytes were inoculated with tachyzoites of T. gondii type II strain ME49.
      Parasite replication was detected by a quantitative real-time PCR at different
      times postinoculation until 24 or 48 h, respectively, displaying long-term
      investigations for the chosen cultures. The parasite replication curve showed a
      continuous decrease of parasite stages in erythrocytes and thrombocytes.
      Observations by light microscopy showed massive destruction for both cell
      populations. Few macrophages in between the infected thrombocytes were viable
      during the investigation period and showed internalised tachyzoites by confocal
      laser scanning microscopy. These findings show that T. gondii is not capable of
      replication in chicken erythrocytes and thrombocytes; therefore, both cannot be
      considered as potential host cells. In further consequence, monocyte-derived
      macrophages seem to be the key to the dissemination mechanisms for T. gondii in
      chicken.

PMID- 27696225
TI  - Recent Scientific Evidence Regarding Asbestos Use and Health Consequences of
      Asbestos Exposure.
AB  - To justify the continuous use of two million tons of asbestos every year, it has
      been argued that a safe/controlled use can be achieved. The aim of this review
      was to identify recent scientific studies that present empirical evidence of: 1)
      health consequences resulting from past asbestos exposures and 2) current
      asbestos exposures resulting from asbestos use. Articles with evidence that could
      support or reject the safe/controlled use argument were also identified. A total
      of 155 articles were included in the review, and 87 % showed adverse asbestos
      health consequences or high asbestos exposures. Regarding the safe/controlled
      use, 44 articles were identified, and 82 % had evidence suggesting that the
      safe/controlled use is not being achieved. A large percentage of articles with
      evidence that support the safe/controlled use argument have a conflict of
      interest declared. Most of the evidence was developed in high-income countries
      and in countries that have already banned asbestos.

PMID- 27696228
TI  - Biomarkers indicate mixture toxicities of fluorene and phenanthrene with
      endosulfan toward earthworm (Eisenia fetida).
AB  - alpha-Endosulfan and some polycyclic aromatic compounds (PAHs) are persistent in
      the environment and can reach crop products via contaminated agricultural soils.
      They may even be present as mixtures in the soil and induce mixture toxicity in
      soil organisms such as earthworms. In this study, the combined toxicities of PAHs
      with alpha-endosulfan were determined in Eisenia fetida adults using an
      artificial soil system. alpha-Endosulfan and five PAHs were tested for their
      acute toxicity toward E. fetida in artificial soils. Only alpha-endosulfan,
      fluorene, and phenanthrene showed acute toxicities, with LC50 values of 9.7,
      133.2, and 86.2 mg kg-1, respectively. A mixture toxicity assay was conducted
      using alpha-endosulfan at LC10 and fluorene or phenanthrene at LC50 in the
      artificial soils. Upon exposure to the mixture of fluorene and alpha-endosulfan,
      earthworms were killed in increasing numbers owing to their synergistic effects,
      while no other mixture showed any additional toxicity toward the earthworms.
      Along with the acute toxicity results, the biochemical and molecular changes in
      the fluorene- and phenanthrene-treated earthworms with or without alpha
      endosulfan treatment demonstrated that enhancement of glutathione S-transferase
      activity was dependent on the addition of PAH chemicals, and the HSP70 gene
      expression increased with the addition of alpha-endosulfan. Taken together, these
      findings contribute toward understanding the adverse effects of pollutants when
      present separately or in combination with other types of chemicals.

PMID- 27696229
TI  - Radon levels in Romanian caves: an occupational exposure survey.
AB  - A comprehensive radon survey has been carried out in seven caves located in the
      western half of Romania's most significant karst regions. Touristic and non
      touristic caves were investigated with the aim to provide a reliable distribution
      of their radon levels and evaluate the occupational exposure and associated
      effective doses. Radon gas concentrations were measured with long-term diffusion
      type detectors during two consecutive seasons (warm and cold). All investigated
      caves exceed the European Union reference level of radon gas at workplaces (300
      Bq/m3). The radon concentration in these caves ranges between 53 and 2866 Bq/m3,
      reflecting particular cave topography, season-related cave ventilation, and
      complex tectonic and geological settings surrounding each location. Relatively
      homogeneous high radon levels occur in all investigated touristic caves and in
      Tausoare and Vantului along their main galleries. Except for Muierii, in all the
      other caves radon levels are higher during the warm season, compared to the cold
      one. This suggests that natural cave ventilation largely controls the underground
      accumulation of radon. The results reported here reveal that the occupational
      exposure in Ursilor, Vadu Crisului, Tausoare, Vantului, and Muierii caves needs
      to be carefully monitored. The effective doses to workers vary between an average
      of 0.25 and 4.39 mSv/year depending on the measuring season. The highest values
      were recorded in show caves, ranging from 1.15 to 6.15 mSv/year, well above the
      European recommended limit, thus posing a potential health hazard upon cave
      guides, cavers, and scientists.

PMID- 27696230
TI  - Is the hypothalamic-pituitary-adrenal axis disrupted in type 2 diabetes mellitus?

PMID- 27696231
TI  - Combination therapy with GLP-1 analogues and SGLT-2 inhibitors in the management
      of diabesity: the real world experience.
AB  - Diabesity-obesity resulting in diabetes-is a major health problem globally
      because of the obesity epidemic. Several anti-diabetic medications cause weight
      gain and may worsen obesity, and possibly diabeisty. Two recent small
      retrospective cohort studies showed weight loss and diabetes improvement with
      combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co
      transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect
      of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the
      management of diabesity in a retrospective study at the Wolverhampton Diabetes
      Centre. Out of 79 patients on this combination regimen with other anti-diabetic
      medications, 37 cases who had follow up at 3-6 months were studied. Mean age and
      duration of follow up were 57.4 (+/-7.8) and 139 (+/-32.6) days, respectively.
      Twenty-two patients (59.5 %) were Asians. Statistically significant improvements
      in clinical parameters such as body weight reduction (3.07 kg), glycated
      haemoglobin (HbA1c) reduction (1.05 %), lower BMI (-1.13 kg/M2) and insulin dose
      reduction (6.8 units) were observed (p < 0.05 for all) in patients on combination
      regimen. Linear regression analysis showed that baseline HbA1c and baseline
      insulin dose were independent predictors of HbA1c reduction and insulin dose
      reduction, respectively. Our results suggest that combination therapy with GLP-1
      agonists and SGLT-2 inhibitors is a promising option for patients with diabesity.

PMID- 27696232
TI  - Correlation of BRAF mutation and SUVmax levels in thyroid cancer patients
      incidentally detected in 18F-fluorodeoxyglucose positron emission tomography.
AB  - The prognostic importance of 18F-fluorodeoxyglucose avidity in primary thyroid
      tumor and molecular basis responsible for its mechanism has not yet been well
      characterized. In this study, we aimed to evaluate the correlation between the
      maximum standardized uptake levels and B-type Raf kinase mutation positivity in
      incidentally detected papillary thyroid cancer patients during 18F
      fluorodeoxyglucose positron emission tomography examination. We retrospectively
      evaluated 6873 18F-fluorodeoxyglucose-positron emission tomography scans of
      consecutive subjects from a database search for tumor staging in 2014 at our
      hospital Nuclear Medicine Center. In total, 135 patients had focal 18F
      fluorodeoxyglucose uptake in the thyroid. Of these, 76 patients had fine-needle
      aspiration biopsy. 18F-fluorodeoxyglucose-maximum standardized uptake of the
      positron emission tomography-detected nodules was recorded. B-type Raf kinase
      (V600E) mutation and p53 protein expression were evaluated in papillary thyroid
      cancer patients. The incidence of thyroid incidentaloma in 18F-fluorodeoxyglucose
      maximum standardized uptake scans was 2 % (135/6873). Of the 76 patients
      evaluated, 41 % (n = 31) were diagnosed papillary thyroid cancer. B-type Raf
      kinase mutation was positive in 51 % (17/30) of the papillary thyroid cancer
      patients. Maximum standardized uptake levels of the nodules (>=1 cm) were
      significantly higher in B-type Raf kinase-mutated papillary thyroid cancer
      patients than in non-mutated patients [16.6 (10.4-27.9) vs. 9.7 (6.8-11.1); P =
      0.007]. Correlation analysis revealed that maximum standardized uptake was
      significantly associated with B-type Raf kinase mutation positivity (r = 0.519; P
      = 0.005). Logistic regression analysis showed an association between maximum
      standardized uptake and B-type Raf kinase mutation positivity even after
      adjustment for age and gender (P = 0.01). B-type Raf kinase mutation is closely
      related to 18F-fluorodeoxyglucose-positron emission tomography maximum
      standardized uptake levels in patients with incidentally detected papillary
      thyroid cancer.

PMID- 27696233
TI  - Clostridium difficile infection in children: epidemiology and risk of recurrence
      in a low-prevalence country.
AB  - Clostridium difficile infection (CDI) is increasingly found in children
      worldwide, but limited data are available from children living in southern
      Europe. A 6-year retrospective study was performed to investigate the
      epidemiology, clinical features, treatment, and risk of recurrence in Italy. Data
      of children with community- and hospital-acquired CDI (CA-CDI and HA-CDI,
      respectively) seen at seven pediatric referral centers in Italy were recorded
      retrospectively. Annual infection rates/10,000 hospital admissions were
      calculated. Logistic regression was used to investigate risk factors for
      recurrence. A total of 177 CDI episodes was reported in 148 children (83 males,
      median age 55.3 months), with a cumulative infection rate of 2.25/10,000
      admissions, with no significant variability over time. The majority of children
      (60.8 %) had CA-CDI. Children with HA-CDI (39.2 %) had a longer duration of
      symptoms and hospitalization (p = 0.003) and a more common previous use of
      antibiotics (p = 0.0001). Metronidazole was used in 70.7 % of cases (87/123) and
      vancomycin in 29.3 % (36/123), with similar success rates. Recurrence occurred in
      16 children (10.8 %), and 3 (2 %) of them presented a further treatment failure.
      The use of metronidazole was associated with a 5-fold increase in the risk of
      recurrence [odds ratio (OR) 5.18, 95 % confidence interval (CI) 1.1-23.8, p =
      0.03]. Short bowel syndrome was the only underlying condition associated with
      treatment failure (OR 5.29, 95 % CI 1.17-23.8, p = 0.03). The incidence of
      pediatric CDI in Italy is low and substantially stable. In this setting, there is
      a limited risk of recurrence, which mainly concerns children treated with oral
      metronidazole and those with short bowel syndrome.

PMID- 27696235
TI  - Clinicians should not be forced to use likelihood ratios when comparing tests.

PMID- 27696236
TI  - Increased local recurrence in advanced parotid malignancy treated with
      mastoidectomy without lateral temporal bone resection.
AB  - OBJECTIVE: We analyzed patients with advanced parotid malignancy requiring
      proximal facial nerve exposure undergoing mastoidectomy versus lateral temporal
      bone resection to determine differences in local and distant recurrence. STUDY
      DESIGN: The study design is a case series with chart review. SETTING: The setting
      is in Tertiary care practice in Fort Worth, Texas from January1998 to January
      2014. SUBJECTS AND METHODS: The study included 120 patients with advanced parotid
      malignancy, 82 males between 19 and 87 years, and 38 females between 26 and 83
      years. Patients with no overt bone involvement were treated with parotidectomy
      and mastoidectomy for exposure of the proximal facial nerve, and patients with
      clinically suspected (radiographic imaging or clinical fixation) bone involvement
      were treated with parotidectomy and lateral temporal bone resection. Follow up
      ranged from a minimum of 18 months to 11 years following surgery. RESULTS: Sixty
      patients were treated with mastoidectomy and 60 were treated with lateral
      temporal bone resection. In patients treated with mastoidectomy, 13 had local
      recurrence and 7 had distal recurrence. In patients treated with lateral temporal
      bone resection, 2 had local recurrence while 9 had distant recurrence.
      Statistical analysis revealed that patients treated with mastoidectomy developed
      local recurrence (p = 0.0022) more commonly than those treated with lateral
      temporal bone resection. There was no significant difference in distant
      recurrence between both groups (p = 0.5949). CONCLUSIONS: Patients with advanced
      parotid malignancy should be treated aggressively with parotidectomy and lateral
      temporal bone resection regardless of bone involvement due to increased risk of
      local recurrence in those treated with mastoidectomy alone. LEVEL OF EVIDENCE:
      Level of evidence is a 4 case series.

PMID- 27696234
TI  - Toxin A-negative toxin B-positive ribotype 017 Clostridium difficile is the
      dominant strain type in patients with diarrhoea attending tuberculosis hospitals
      in Cape Town, South Africa.
AB  - The molecular epidemiology of C. difficile strains causing disease in South
      Africa is currently unknown. Previously, multidrug resistant ribotype (RT)017
      strains were those most commonly isolated from patients with diarrhoea attending
      Groote Schuur Hospital in Cape Town, South Africa. This larger study aimed to
      investigate the molecular epidemiology and antibiotic susceptibility profiles of
      C. difficile strains in the greater Cape Town and regional areas. C. difficile
      strains were isolated from patients with diarrhoea attending hospitals in the
      Western Cape region of South Africa that tested positive using the GeneXpert
      CDiff diagnostic test. Ribotyping and multilocus variable-number tandem-repeat
      analysis (MLVA) were used to type isolates, and their susceptibilities to several
      antibiotics were determined by gradient diffusion test strips. A total of 269 non
      repeat C. difficile isolates were obtained. A large proportion of isolates (64.3
      %) belonged to the RT017 group, many of which were clonally related when
      investigated by MLVA. RT017 strains were particularly prevalent in patients
      attending specialist tuberculosis (TB) hospitals. The majority of RT017 isolates
      were co-resistant to moxifloxacin and rifampicin, two antibiotics which are used
      intensively during anti-TB therapy. Non-RT017 strains were generally susceptible
      to both antibiotics. Resistance to erythromycin was observed for both groups of
      strains. RT017 C. difficile strains are the most commonly isolated strains from
      patients attending healthcare facilities in the greater Cape Town and regional
      areas. The presence of multidrug resistant RT017 strains in patients with
      diarrhoea attending local TB hospitals reflects a potential reservoir for future
      infections.

PMID- 27696237
TI  - Global Changes in Food Supply and the Obesity Epidemic.
AB  - PURPOSE OF REVIEW: We explore how a global shift in the food system caused by
      global economic growth, increase in available food per capita and in food
      processing is a driver of the obesity epidemic. RECENT FINDINGS: Economic
      development in most areas of the world has resulted in increased purchasing power
      and available per capita food. Supermarkets and a growing fast-food industry have
      transformed our dietary pattern. Ultra-processed food rich on sugars and
      saturated fat is now the major source of energy in most countries. The shift in
      food supply is considered a major driver of the obesity epidemic and the
      increasing prevalence of accompanying complications, such as type 2 diabetes,
      cardiovascular disease and cancer. However, the global shift might also have
      direct effects on the increase in type 2 diabetes, cardiovascular disease and
      cancer, independently of overweight and obesity. The shift in the food supply is
      a major driver of the obesity epidemic.

PMID- 27696238
TI  - Embryonic kidney function in a chronic renal failure model in rodents.
AB  - BACKGROUND: Rapid advancements have been made in alternative treatments for renal
      diseases. Our goal for renal regeneration is to establish a kidney graft derived
      from human embryonic tissues. In this study, we investigated the effects of host
      renal failure on the structure and activity of transplanted embryonic kidney and
      bladder, and found that diuretics effectively induced urine production in the
      transplanted kidney. METHODS: Uremic conditions were reproduced using a 5/6 renal
      infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was
      isolated from a pregnant Lewis rat and transplanted into the para-aortic area of
      a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was
      successfully anastomosed to the host ureter. RESULTS: We assessed graft function
      in terms of survival rates and found no differences between normal (n = 5) and
      renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in
      terms of survival, indicating that the grafts prolonged rat survival, even under
      renal failure conditions. Furosemide (n = 9) significantly increased urine volume
      compared with saline-treated controls (n = 7; p < 0.05), confirming that the
      grafts were functional. We also demonstrated the possibilities of an in vivo
      imaging system for determining the viability of transplanted embryonic kidney
      with bladder. CONCLUSION: The results of this study demonstrate that transplanted
      embryonic kidney and bladder can grow and function effectively, even under uremic
      conditions.

PMID- 27696240
TI  - D3R grand challenge 2015: Evaluation of protein-ligand pose and affinity
      predictions.
AB  - The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September
      2015 and February 2016. Two targets served as the framework to test community
      docking and scoring methods: (1) HSP90, donated by AbbVie and the Community
      Structure Activity Resource (CSAR), and (2) MAP4K4, donated by Genentech. The
      challenges for both target datasets were conducted in two stages, with the first
      stage testing pose predictions and the capacity to rank compounds by affinity
      with minimal structural data; and the second stage testing methods for ranking
      compounds with knowledge of at least a subset of the ligand-protein poses. An
      additional sub-challenge provided small groups of chemically similar HSP90
      compounds amenable to alchemical calculations of relative binding free energy.
      Unlike previous blinded Challenges, we did not provide cognate receptors or
      receptors prepared with hydrogens and likewise did not require a specified
      crystal structure to be used for pose or affinity prediction in Stage 1. Given
      the freedom to select from over 200 crystal structures of HSP90 in the PDB,
      participants employed workflows that tested not only core docking and scoring
      technologies, but also methods for addressing water-mediated ligand-protein
      interactions, binding pocket flexibility, and the optimal selection of protein
      structures for use in docking calculations. Nearly 40 participating groups
      submitted over 350 prediction sets for Grand Challenge 2015. This overview
      describes the datasets and the organization of the challenge components,
      summarizes the results across all submitted predictions, and considers broad
      conclusions that may be drawn from this collaborative community endeavor.

PMID- 27696239
TI  - A combined treatment of hydration and dynamical effects for the modeling of host
      guest binding thermodynamics: the SAMPL5 blinded challenge.
AB  - As part of the SAMPL5 blinded experiment, we computed the absolute binding free
      energies of 22 host-guest complexes employing a novel approach based on the BEDAM
      single-decoupling alchemical free energy protocol with parallel replica exchange
      conformational sampling and the AGBNP2 implicit solvation model specifically
      customized to treat the effect of water displacement as modeled by the Hydration
      Site Analysis method with explicit solvation. Initial predictions were affected
      by the lack of treatment of ionic charge screening, which is very significant for
      these highly charged hosts, and resulted in poor relative ranking of negatively
      versus positively charged guests. Binding free energies obtained with Debye
      Huckel treatment of salt effects were in good agreement with experimental
      measurements. Water displacement effects contributed favorably and very
      significantly to the observed binding affinities; without it, the modeling
      predictions would have grossly underestimated binding. The work validates the
      implicit/explicit solvation approach employed here and it shows that
      comprehensive physical models can be effective at predicting binding affinities
      of molecular complexes requiring accurate treatment of conformational dynamics
      and hydration.

PMID- 27696241
TI  - Effects of point mutations on the thermostability of B. subtilis lipase:
      investigating nonadditivity.
AB  - Molecular level understanding of mutational effects on stability and activity of
      enzymes is challenging particularly when several point mutations are incorporated
      during the directed evolution experiments. In our earlier study, we have
      suggested the lack of consistency in the effect of point mutations incorporated
      during the initial generations of directed evolution experiments, towards
      conformational stabilization of B. subtilis lipase mutants of later generations.
      Here, we report that the cumulative point mutations incorporated in mutants 2M
      (with two point mutations) to 6M (with six point mutations) possibly do not
      retain their original stabilizing nature in the most thermostable 12M mutant
      (with 12 point mutations). We have carried out MD simulations using structures
      incorporating reversal of different sets of point mutations to assess their
      effect on the conformational stability and activity of 12M. Our analysis has
      revealed that reversal of certain point mutations in 12M had little effect on its
      conformational stability, suggesting that these mutations were probably
      inconsequential towards the thermostability of the 12M mutant. Interestingly
      these mutations involved evolutionarily conserved residues. On the other hand,
      some of the other point mutations incorporated in nonconserved regions, appeared
      to contribute significantly towards the conformational stability and/or activity
      of 12M. Based on the analysis of dynamics of in silico mutants generated using
      the consensus sequence, we identified experimentally verifiable residue positions
      to further increase the conformational stability and activity of the 12M mutant.

PMID- 27696242
TI  - Absolute binding free energies for octa-acids and guests in SAMPL5 : Evaluating
      binding free energies for octa-acid and guest complexes in the SAMPL5 blind
      challenge.
AB  - As part of the SAMPL5 blind prediction challenge, we calculate the absolute
      binding free energies of six guest molecules to an octa-acid (OAH) and to a
      methylated octa-acid (OAMe). We use the double decoupling method via
      thermodynamic integration (TI) or Hamiltonian replica exchange in connection with
      the Bennett acceptance ratio (HREM-BAR). We produce the binding poses either
      through manual docking or by using GalaxyDock-HG, a docking software developed
      specifically for this study. The root mean square deviations for our most
      accurate predictions are 1.4 kcal mol-1 for OAH with TI and 1.9 kcal mol-1 for
      OAMe with HREM-BAR. Our best results for OAMe were obtained for systems with
      ionic concentrations corresponding to the ionic strength of the experimental
      solution. The most problematic system contains a halogenated guest. Our attempt
      to model the sigma-hole of the bromine using a constrained off-site point charge,
      does not improve results. We use results from molecular dynamics simulations to
      argue that the distinct binding affinities of this guest to OAH and OAMe are due
      to a difference in the flexibility of the host. We believe that the results of
      this extensive analysis of host-guest complexes will help improve the protocol
      used in predicting binding affinities for larger systems, such as protein
      substrate compounds.

PMID- 27696243
TI  - Social Support, Parenting, and Social Emotional Development in Young Mexican and
      Dominican American Children.
AB  - This study focused on social support and its association with child developmental
      outcomes, indirectly through parenting practices, in families of 4-5 year old
      Latino children. Data were collected from mothers and teachers of 610 Mexican
      American (MA) and Dominican American (DA) children. Mothers reported on perceived
      social support, parenting practices and children's problem and adaptive behavior
      functioning at home, and teachers reported on mothers' parent involvement and
      children's problem and adaptive behavior functioning in the classroom. Results
      showed that support received from family was higher than support received from
      school networks for both ethnic groups. Moreover, familial support was associated
      with child behavior, mediated by positive parenting practices, whereas support
      from school networks was not associated with child outcomes. During early
      childhood, social support from family members may be an important protective
      factor that can promote positive behavioral functioning among Latino children.

PMID- 27696244
TI  - In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is
      associated with adverse clinico-pathological features.
AB  - Attempts at identification of an ideal prognostic/predictive biomarker in
      phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit
      expression in PT have shown contradictory results. Recently aldehyde
      dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT
      but its expression has not been studied in benign and borderline tumours. We
      aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in
      different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were
      studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with
      different clinico-pathological features and recurrence rates. Stromal c-kit
      expression at 1 % cutoff correlated with increasing tumour grade, larger tumour
      size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins
      and mitotic count. These associations, however, were lost with higher (5 or 10 %)
      cutoffs. Conversely, decreased c-kit expression in the epithelial component
      correlated with increasing tumour grade, regardless of the cutoffs used. Stromal
      ALDH1A1 expression did not have significant associations with tumour grade or
      other adverse clinico-pathological features, regardless of different cutoffs.
      None of the cases showed significant epithelial ALDH1A1 expression. Expression of
      c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1
      expression was associated with shorter recurrence-free survival (p = 0.036). In
      conclusion, c-kit expression was associated with higher tumour grade and adverse
      clinico-pathological features. However, these associations are cutoff dependent,
      partly explaining the variability in previously reported studies. ALDH1A1
      expression did not have significant correlations with tumour grade and adverse
      clinico-pathological variables.

PMID- 27696245
TI  - Immunophenotypic differences between neoplastic and non-neoplastic androgen
      producing cells containing and lacking Reinke crystals.
AB  - We performed a detailed morphologic, immunophenotypic, and endocrine
      characterization of neoplastic and non-neoplastic lesions of androgen-producing
      cells known to harbor or lack Reinke crystals (RCs) with an aim to provide
      further insight into the nature of these cells and crystals. Study cases were
      selected from the files of participating hospitals and subclassified according to
      current classifications: 20 with Leydig cell tumors (LCTs), 2 with testicular
      adrenal rest tumors (TARTs), 2 with testicular tumors of adrenogenital syndrome
      (TTAGS), and 2 with androgen insensitivity syndrome (AIS). An extensive
      immunophenotypic panel including markers used in sex cord-stromal cell tumors,
      androgen hormones, enzymes, and receptors was applied to the cases and 10 non
      tumoral adrenal glands. Non-tumoral tissues were scored separately. RCs were
      present in 90 % of LCT cases and all cases with normal Leydig cells; RCs stained
      specifically with calretinin and 3beta-hydroxysteroid dehydrogenase (3BHSD) and
      were present only in cells with high concomitant expression of both proteins, a
      phenotype unique to Leydig cells and LCTs. Leydig cells from AIS cases lack RCs
      due to decreased expression of 3BHSD. Calretinin is decreased in testicular
      adrenal-like tumors and absent in normal adrenocortical cells, which explain why
      they lack RCs. Calretinin expression in androgen-producing cells is independent
      from androgen receptors and androgen synthesis. RCs represent for the most part,
      if not exclusively, crystallized forms of a 3BHSD/calretinin complex. Androgen
      producing cells containing and lacking RCs differ mainly in the level of
      expression of these proteins and androgen receptors.

PMID- 27696246
TI  - The Importance of Properly Compensating for Head Movements During MEG Acquisition
      Across Different Age Groups.
AB  - Unlike EEG sensors, which are attached to the head, MEG sensors are located
      outside the head surface on a fixed external device. Subject head movements
      during acquisition thus distort the magnetic field distributions measured by the
      sensors. Previous studies have looked at the effect of head movements, but no
      study has comprehensively looked at the effect of head movements across age
      groups, particularly in infants. Using MEG recordings from subjects ranging in
      age from 3 months through adults, here we first quantify the variability in head
      position as a function of age group. We then combine these measured head
      movements with brain activity simulations to determine how head movements bias
      source localization from sensor magnetic fields measured during movement. We find
      that large amounts of head movement, especially common in infant age groups, can
      result in large localization errors. We then show that proper application of head
      movement compensation techniques can restore localization accuracy to pre
      movement levels. We also find that proper noise covariance estimation (e.g.,
      during the baseline period) is important to minimize localization bias following
      head movement compensation. Our findings suggest that head position measurement
      during acquisition and compensation during analysis is recommended for
      researchers working with subject populations or age groups that could have
      substantial head movements. This is especially important in infant MEG studies.

PMID- 27696247
TI  - Characterization of the spatial variability of soil available zinc at various
      sampling densities using grouped soil type information.
AB  - The influence of anthropogenic activities and natural processes involved high
      uncertainties to the spatial variation modeling of soil available zinc (AZn) in
      plain river network regions. Four datasets with different sampling densities were
      split over the Qiaocheng district of Bozhou City, China. The difference of AZn
      concentrations regarding soil types was analyzed by the principal component
      analysis (PCA). Since the stationarity was not indicated and effective ranges of
      four datasets were larger than the sampling extent (about 400 m), two
      investigation tools, namely F3 test and stationarity index (SI), were employed to
      test the local non-stationarity. Geographically weighted regression (GWR)
      technique was performed to describe the spatial heterogeneity of AZn
      concentrations under the non-stationarity assumption. GWR based on grouped soil
      type information (GWRG for short) was proposed so as to benefit the local
      modeling of soil AZn within each soil-landscape unit. For reference, the multiple
      linear regression (MLR) model, a global regression technique, was also employed
      and incorporated the same predictors as in the GWR models. Validation results
      based on 100 times realization demonstrated that GWRG outperformed MLR and can
      produce similar or better accuracy than the GWR approach. Nevertheless, GWRG can
      generate better soil maps than GWR for limit soil data. Two-sample t test of
      produced soil maps also confirmed significantly different means. Variogram
      analysis of the model residuals exhibited weak spatial correlation, rejecting the
      use of hybrid kriging techniques. As a heuristically statistical method, the GWRG
      was beneficial in this study and potentially for other soil properties.

PMID- 27696248
TI  - Influences of the Results from STRIVE Trial on the Combination Androgen Depletion
      Therapy for Advanced Prostate Cancer.
AB  - The clinical efficacy of combined therapy (CAB) has been clearly recognized by
      the results of the STRIVE trial. Although enzalutamide has shown a stronger
      effect on CRPC, bicultamide, a classical anti-androgen, has shown a significant
      effect. In addition, it can be deduced that CAB is a strong tool for hormone
      naive advanced prostate cancer. Cost-effective evaluation for CAB with
      bicultamide or enzalutamide is warranted, especially for the resource-limited
      cohort.

PMID- 27696249
TI  - Adoption consideration and concerns among young adult female cancer survivors.
AB  - PURPOSE: We compared adoption consideration between female young adult cancer
      survivors and women of the same age in the general US population, hypothesizing
      that cancer survivors who desired children would report greater interest in
      adoption than an age-adjusted general population sample who desired children.
      METHODS: After age-standardizing the cancer survivor cohort to match the age
      distribution of the 2006-2010 National Survey for Family Growth (NSFG), we
      estimated adoption consideration among women age 18-35 years who wanted a
      (another) child in the two cohorts overall and within age groups. We assessed
      characteristics and concerns related to adoption consideration among cancer
      survivors. RESULTS: Among cancer survivors, 81.6 % (95 % CI 75.7-87.6) reported
      that they would consider adoption compared to 40.3 % (95 % CI 40.3-40.3) of women
      in the general population. While over 80 % of the cancer survivor sample reported
      that they would consider adoption, only 15 % of cancer survivors reported no
      concerns about adoption. The most common concerns were desire for a biological
      child (48 %), expense (45 %), adoption agency candidacy (41 %), and needing more
      information (39 %). CONCLUSION: We observed a twofold higher interest in adoption
      when comparing the cancer survivor with the general population, suggesting that
      adoption is a consideration for many young women who have survived cancer.
      IMPLICATIONS FOR CANCER SURVIVORS: Adoption is an important family-building
      option for those who want to have a child but are unable to or choose not to have
      a biological child. However, young adult survivors may need more support to
      understand and navigate this process.

PMID- 27696250
TI  - "Physical exercise and dementia in patients with type 2 diabetes mellitus".
      Authors' reply.

PMID- 27696251
TI  - Targeted next-generation sequencing for TP53, RAS, BRAF, ALK and NF1 mutations in
      anaplastic thyroid cancer.
AB  - Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer with a
      median survival of 4-6 months. Identification of mutations contributing to
      aberrant activation of signaling cascades in ATC may provide novel opportunities
      for targeted therapy. Thirty-nine ATC samples were studied by next-generation
      sequencing (NGS) with an established gene panel. High quality readout was
      obtained in 30/39 ATC. Twenty-eight ATC harbored a mutation in at least one of
      the studied genes: TP53 (18/30), NF1 (11/30), ALK (6/30), NRAS (4/30), ATRX
      (3/30), BRAF (2/30), HRAS (2/30), KRAS (1/30). In 17/30 ATC (54 %) mutations were
      found in two or more genes. Twenty-one of the identified variants are listed in
      COSMIC as somatic mutations reported in other cancer entities. In three ATC
      samples no mutations were detected and none of the ATCs was positive for
      BRAFV600E. The most frequent mutations were found in TP53 (60 %), followed by NF1
      (37 %). ALK mutations were detected in 20 % of ATC and were more frequent than
      RAS or BRAF mutations. ATRX mutations were identified in 10 % of the ATC samples.
      These sequencing data from 30 ATC samples demonstrate the accumulation of genetic
      alterations in ATC because in 90 % of samples mutations were already found in the
      investigated nine genes alone. Mutations were found with high prevalence in
      established tumor suppressor and oncogenes in ATC, such as TP53 and H/K/NRAS, but
      also, although less frequent, in genes that may harbor the potential for targeted
      treatment in a subset of ATC patients, such as ALK and NF1.

PMID- 27696252
TI  - Chronic hyperglycemia affects bone metabolism in adult zebrafish scale model.
AB  - Type II diabetes mellitus is a metabolic disease characterized by chronic
      hyperglycemia that induce other pathologies including diabetic retinopathy and
      bone disease. The mechanisms implicated in bone alterations induced by type II
      diabetes mellitus have been debated for years and are not yet clear because there
      are other factors involved that hide bone mineral density alterations. Despite
      this, it is well known that chronic hyperglycemia affects bone health causing
      fragility, mechanical strength reduction and increased propensity of fractures
      because of impaired bone matrix microstructure and aberrant bone cells function.
      Adult Danio rerio (zebrafish) represents a powerful model to study glucose and
      bone metabolism. Then, the aim of this study was to evaluate bone effects of
      chronic hyperglycemia in a new type II diabetes mellitus zebrafish model created
      by glucose administration in the water. Fish blood glucose levels have been
      monitored in time course experiments and basal glycemia was found increased.
      After 1 month treatment, the morphology of the retinal blood vessels showed
      abnormalities resembling to the human diabetic retinopathy. The adult bone
      metabolism has been evaluated in fish using the scales as read-out system. The
      scales of glucose-treated fish didn't depose new mineralized matrix and shown
      bone resorption lacunae associated with an intense osteoclast activity. In
      addition, hyperglycemic fish scales have shown a significant decrease of alkaline
      phosphatase activity and increase of tartrate-resistant acid phosphatase
      activity, in association with alterations in other bone-specific markers. These
      data indicates an imbalance in bone metabolism, which leads to the osteoporotic
      like phenotype visualized through scale mineral matrix staining. The zebrafish
      model of hyperglycemic damage can contribute to elucidate in vivo the molecular
      mechanisms of metabolic changes, which influence the bone tissues regulation in
      human diabetic patients.

PMID- 27696253
TI  - Vitamin D and gallstone disease-A population-based study.
AB  - Gallstone disease is highly prevalent in the general population and is a major
      gastrointestinal cause of hospital admissions. The objectives were to determine
      whether circulating levels of 25-hydroxyvitamin D were associated to ultrasound
      proven gallstones or cholecystectomy in a general population sample. Determinants
      of vitamin D status were also explored. A random sample of 4130 people from the
      population of Copenhagen with ages 41-71 years were invited (N = 4130) and 2650
      participants were included. Ultrasound examinations were performed to assess
      gallstone status and blood samples were drawn to assess 25-hydroxyvitamin D and
      biomarkers of renal and hepatic function. Gallstone disease was found in 422
      participants. Associations were estimated by logistic regression models. Levels
      of 25-hydroxyvitamin D was not significantly associated with gallstone disease.
      Time of birth during low vitamin D exposure was associated with gallstone disease
      (gallstone prevalence 18.0 versus 14.4 %, odds ratio 1.33, 95 % confidence
      interval [1.07; 1.65]). Highest quartile of cystatin C was significantly
      associated with gallstone disease (gallstone prevalence 22.1 versus 12.0 %, odds
      ratio 1.53, 95 % confidence interval [1.08; 2.18]). Serum levels of creatinine
      and alanine amino transferase were not associated with gallstone disease.
      Sensitivity analyses excluding participants with cholecystectomy did not alter
      results significantly. No association between 25-hydroxyvitamin D and gallstone
      disease was identified. Findings suggest gallstones to be associated to low
      vitamin D exposure in utero and to renal failure suggesting that vitamin D might
      have an impact on gallstone disease. Future studies should explore associations
      for vitamin D and gallstone disease prospectively.

PMID- 27696254
TI  - MGUS and Smoldering Multiple Myeloma: Diagnosis and Epidemiology.
AB  - Monoclonal gammopathy of undetermined significance (MHUS) is characterized by the
      presence of a serum M-protein less than 3 g/dL, less than 10 % clonal plasma
      cells in the bone marrow, and the absence of myeloma-defining event. Smoldering
      multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence
      of >=3 g/dL serum M-protein and/or 10-60 % bone marrow plasma cell infiltration
      with no myeloma-defining event. The risk of progression to multiple myeloma (MM)
      requiring therapy varies greatly for individual patients, but it is uniform and 1
      % per year for MGUS, while higher (10 % per year) and not uniform for SMM
      patients. The definition of MM was recently revisited patients previously labeled
      as SMM with a very high risk of progression (80-90 % at 2 years) were included in
      the updated definition of MM requiring therapy. The standard of care is
      observation for MGUS patients and although this also applies for SMM, a recent
      randomized trial targeting high-risk SMM showed that early intervention was
      associated with better progression-free and overall survival. Biomarkers have
      become an integrated part of diagnostic criteria for MM requiring therapy, as
      well as clinical risk stratification of patients with SMM. This paper reviews and
      discusses clinical implications for MGUS and SMM patients.

PMID- 27696255
TI  - Vision Statement for Multiple Myeloma: Future Directions.
AB  - There has been great progress in the management and patient outcome in multiple
      myeloma due to the use of novel agents including immunomodulatory drugs and
      proteasome inhibitors; nonetheless, novel agents remain an urgent need. The three
      promising Achilles heals or vulnerabilities to be targetted in novel therapies
      include: protein degradation by the ubiquitin proteasome or aggresome pathways;
      restoring autologous antimyeloma immunity; and targeting aberrant biology
      resulting from constitutive and ongoing DNA damage in tumour cells.
      Scientifically based therapies targeting these vulnerabilities used early in the
      disease course, ie smouldering multiple myeloma, have the potential to
      significantly alter the natural history and transform myeloma into a chronic and
      potentially curable disease.

PMID- 27696256
TI  - Genomic Aberrations in Multiple Myeloma.
AB  - Multiple myeloma (MM) is a genetically complex disease. The past few years have
      seen an evolution in cancer research with the emergence of next-generation
      sequencing (NGS), enabling high throughput sequencing of tumors-including whole
      exome, whole genome, RNA, and single-cell sequencing as well as genome-wide
      association study (GWAS). A few inherited variants have been described, counting
      for some cases of familial disease. Hierarchically, primary events in MM can be
      divided into hyperdiploid (HDR) and nonhyperdiploid subtypes. HRD tumors are
      characterized by trisomy of chromosomes 3, 5, 7, 9, 11, 15, 19, and/or 21. Non
      HRD tumors harbor IGH translocations, mainly t(4;14), t(6;14), t(11;14),
      t(14;16), and t(14;20). Secondary events participate to the tumor progression and
      consist in secondary translocation involving MYC, copy number variations (CNV)
      and somatic mutations (such as mutations in KRAS, NRAS, BRAF, P53). Moreover, the
      dissection of clonal heterogeneity helps to understand the evolution of the
      disease. The following review provides a comprehensive review of the genomic
      landscape in MM.

PMID- 27696257
TI  - Epigenetics in Multiple Myeloma.
AB  - Multiple myeloma is characterized by clonal proliferation of plasma cells within
      the bone marrow resulting in anemia, lytic bone lesions, hypercalcemia, and renal
      impairment. Despite advanced in our understanding of this complex disease in
      recent years, it is still considered an incurable malignancy. This is, in part,
      due to the highly heterogenous genomic and phenotypic nature of the disease,
      which is to date incompletely understood. It is clear that a deeper level of
      knowledge of the biological events underlying the development of these diseases
      is needed to identify new targets and generate effective novel therapies.
      MicroRNAs (miRNAs), which are single strand, 20-nucleotide, noncoding RNA's, are
      key regulators of gene expression and have been reported to exert transcriptional
      control in multiple myeloma. miRNAs are now recognized to play a role in many key
      areas such as cellular proliferation, differentiation, apoptosis and stress
      response. Substantial advances have been made in recent years in terms of our
      understanding of the biological role of miRNAs in a diverse range of
      hematological and solid malignancues, In multiple myeloma these advances have
      yielded new information of prognostic and diagnostic relevance which have helped
      to shed light on epigenetic regulation in this disease.

PMID- 27696258
TI  - Role of Endothelial Cells and Fibroblasts in Multiple Myeloma Angiogenic Switch.
AB  - Multiple myeloma (MM) mainly progresses in bone marrow (BM). Therefore, signals
      from the BM microenvironment are thought to play a critical role in maintaining
      plasma cell growth, migration, and survival. Reciprocal positive and negative
      interactions between plasma cells and microenvironmental cells, including
      endothelial cells (ECs) and fibroblasts may occur. The BM neovascularization is a
      constant hallmark of MM, and goes hand in hand with progression to leukemic
      phase. Microenvironmental factors induce MMECs and fibroblasts to become
      functionally different from monoclonal gammopathy of undetermined significance
      (MGUS) ECs (MGECs), i.e., to acquire an overangiogenic phenotype, and be similar
      to transformed cells. These alterations play an important role in MM progression
      and may represent new molecular markers for prognostic stratification of patients
      and prediction of response to antiangiogenic drugs, as well as new potential
      therapeutic targets.

PMID- 27696259
TI  - Targeting the Bone Marrow Microenvironment.
AB  - Unprecedented advances in multiple myeloma (MM) therapy during the last 15 years
      are predominantly based on our increasing understanding of the pathophysiologic
      role of the bone marrow (BM) microenvironment. Indeed, new treatment paradigms,
      which incorporate thalidomide, immunomodulatory drugs (IMiDs), and proteasome
      inhibitors, target the tumor cell as well as its BM microenvironment. Ongoing
      translational research aims to understand in more detail how disordered BM-niche
      functions contribute to MM pathogenesis and to identify additional derived
      targeting agents. One of the most exciting advances in the field of MM treatment
      is the emergence of immune therapies including elotuzumab, daratumumab, the
      immune checkpoint inhibitors, Bispecific T-cell engagers (BiTes), and Chimeric
      antigen receptor (CAR)-T cells. This chapter will review our knowledge on the
      pathophysiology of the BM microenvironment and discuss derived novel agents that
      hold promise to further improve outcome in MM.

PMID- 27696260
TI  - Multiple Myeloma Minimal Residual Disease.
AB  - Assessment of minimal residual disease (MRD) is becoming standard diagnostic care
      for potentially curable neoplasms such as some acute leukemias as well as chronic
      myeloid and lymphocytic leukemia. Although multiple myeloma (MM) remains as an
      incurable disease, around half of the patients achieve complete remission (CR),
      and recent data suggests increasing rates of curability with "total-therapy-like"
      programs. This landscape is likely to be improved with the advent of new
      antibodies and small molecules. Therefore, conventional serological and
      morphological techniques have become suboptimal for sensitive evaluation of
      highly effective treatment strategies. Although, existing data suggests that MRD
      could be used as a biomarker to evaluate treatment efficacy, help on therapeutic
      decisions, and act as surrogate for overall survival, the role of MRD in MM is
      still a matter of extensive debate. Here, we review the different levels of
      remission used to define depth of response in MM and their clinical significance,
      as well as the prognostic value and unique characteristics of MRD detection using
      immunophenotypic, molecular, and imaging techniques. Key facts The higher
      efficacy of new treatment strategies for MM demand the incorporation of highly
      sensitive techniques to monitor treatment efficacy MRD could be used as a more
      potent surrogate biomarker for survival than standard CR We need to understand
      the pros and cons of the different MRD techniques The time has come to
      incorporate highly sensitive, cost-effective, readily available, and standardized
      MRD techniques into clinical trials to assess its role in therapeutic decisions.

PMID- 27696261
TI  - Treatment of Newly Diagnosed Elderly Multiple Myeloma.
AB  - Multiple myeloma (MM) is a disease of the elderly, with a median age at diagnosis
      of approximately 70 years old, and more than 30 % of patients aged >75 years.
      This latter and very elderly population is going to significantly rise in the
      near future given the increase in life expectancy in Western countries, and, most
      importantly, global health status of elderly patients is improving, justifying
      appropriate treatments. Changes in treatment paradigm from the old melphalan
      prednisone regimen used since the 1970s to its use as a backbone in a
      nontransplant setting since the late 1990s have highlighted different subgroups
      in elderly MM. Some "elderly" patients could be treated like transplant eligible
      patients, more likely those aged between 65 and the early 70; while a second
      group would rather be referred to current approved treatment regimens for the non
      transplant setting. A dose-intensity approach seems reasonable for this group,
      aiming for the best response, eventually the complete response (CR) or even
      minimal residual disease (MRD). The advent of novel agents such as thalidomide,
      bortezomib, and most recently lenalidomide have allowed a major improvement in
      outcome as compared to historical combinations, and soon the novel class of
      monoclonal antibodies should help to further improve these patients' survival.
      Nonetheless, elderly patients are more susceptible to side effects and are often
      unable to tolerate full drug doses, and thus require lower dose intensity
      regimens, or novel drugs or combinations with more favourable safety profile.
      Recent developments in MM have focused on identifying these vulnerable patients
      through geriatric assessment and novel myeloma scoring system, including the
      notions of frailty, disability and comorbidities. Eventually, we have reached an
      era in which we should be able to provide individualized treatment strategies and
      drug doses-"tailored therapy"-to improve tolerability and optimize efficacy and
      ultimately survival for most elderly MM patients.

PMID- 27696262
TI  - Management of Transplant-Eligible Patients with Newly Diagnosed Multiple Myeloma.
AB  - Treatment approaches for newly diagnosed myeloma have changed considerably during
      the past decade, along with a better understanding of the disease heterogeneity.
      Availability of new drug classes such as proteasome inhibitors and
      immunomodulatory drugs, and use of these drugs in combinations have led to higher
      response rates and deeper responses in the vast majority of patients with newly
      diagnosed myeloma. In addition to improved efficacy, these regimens are tolerated
      better than those with conventional chemotherapy drugs, which have reduced the
      early mortality seen in MM, while allowing for successful stem cell collection in
      patients undergoing stem cell transplant consolidation. Ongoing clinical trials
      with newer drugs such as monoclonal antibodies are being explored as options for
      newly diagnosed MM. The optimal regimen continues to evolve and is often dictated
      by the intent to transplant, age and comorbidities. Despite the increasing
      response rates seen with the new regimens, autologous stem cell transplantation
      remains an effective modality for consolidation, further deepening the responses
      seen with the initial therapy. Post-transplant approaches have further added to
      the efficacy of this platform with both post-transplant consolidation and
      maintenance demonstrating value in clinical trials. Currently, the combination of
      an effective initial therapy followed by one or two autologous stem cell
      transplants, with or without consolidation followed by maintenance appear to
      provide the maximum benefit in terms of duration of disease control for patients
      with newly diagnosed MM.

PMID- 27696263
TI  - Treatment of Relapsed/Refractory Multiple Myeloma.
AB  - Survival outcomes of patients with Multiple Myeloma (MM) have improved over the
      last decade due to the introduction of novel agents such as the immunomodulatory
      drugs thalidomide, lenalidomide (Len) and pomalidomide, and the proteasome
      inhibitors bortezomib (BTZ) and carfilzomib [1, 2]. However, despite these major
      advances, MM remains largely incurable and almost all patients relapse and
      require additional therapy [3]. The successful introduction of next generation
      novel agents including oral proteasome inhibitors, deacetylase inhibitors, and
      especially monoclonal antibodies as part of immunotherapy promises to further
      improve outcome.

PMID- 27696264
TI  - Treatment of MM: Upcoming Novel Therapies.
AB  - Treatment for myeloma has dramatically changed over the past decade, as has
      overall survival, due in large part to the development of new targeted agents.
      While proteasome inhibitors and immunomodulatory agents have contributed to
      improved outcomes, additional new options remain an unmet medical need. Classes
      of emerging agents include those targeting epigenetics, such as histone
      deacetylase inhibitors, monoclonal antibodies, and other emerging targets, such
      as kinesin spindle protein (KSP) inhibitors, cyclin dependent kinase (CDK)
      inhibitors, and nuclear protein export inhibitors. Future treatment approaches
      will need to identify how and when to incorporate these treatment options to
      optimally treat patients with relapsed or refractory myeloma.

PMID- 27696265
TI  - Role of the Immune Response in Disease Progression and Therapy in Multiple
      Myeloma.
AB  - Multiple myeloma (MM) is a hematologic cancer derived from malignant plasma cells
      within the bone marrow. Unlike most solid tumors, which originate from epithelial
      cells, the myeloma tumor is a plasma cell derived from the lymphoid cell lineage
      originating from a post-germinal B-cell. As such, the MM plasma cell represents
      an integral component of the immune system in terms of both antibody production
      and antigen presentation, albeit not efficiently. This fundamental difference has
      significant implications when one considers the implications of immunotherapy. In
      the case of lymphoid malignancies such as myeloma, immune-based strategies must
      take into consideration this important difference, potentially necessitating
      immunotherapy targeted toward MM to be altered from that targeted at solid
      tumors. Typically, the immune system "surveys" cells within our body and is able
      to recognize and attack cancerous cells that may arise. However, some cancer
      cells are able to evade immune surveillance and continue to flourish, causing
      disease. The major mechanism leading to an effective tumor-specific response is
      one that enables effective antigen processing and presentation with subsequent T
      cell activation, expansion, and effective trafficking to the tumor site. Plasma
      cells employ several mechanisms to escape immune surveillance which include
      altered interactions with T-cells, DCs, bone marrow stromal cells (BMSC's), and
      natural killer cells (NK Cells) that can be mediated by immunosuppressive cells
      such as and myeloid-derived suppressor cells (MDSC's) and cytokines such as IL
      10, TGFbeta, and IL-6 as well as down-regulation of the antigen processing
      machinery. Many therapies have been developed to reestablish a functional immune
      system in MM patients. These include adoptive T-cell therapies to deliver more
      tumor-specific T-cells, vaccines to increase the tumor-specific precursor
      frequency of the endogenous T-cell population, immunomodulatory agents (IMiDs)
      such as thalidomide and lenalidomide to enhance global endogenous immunity,
      immunostimulatory cytokines, and antibodies to specifically target tumor-specific
      cell-surface proteins or cytokines. This review will dissect these various
      approaches currently being explored in MM as well as highlight some future
      directions for myeloma-specific immune-based strategies.

PMID- 27696266
TI  - Transplantation for Multiple Myeloma.
AB  - Multiple myeloma is a disorder characterized by accumulation of malignant plasma
      cells in the bone marrow, hypercalcemia, monoclonal protein, and end organ
      damage. Recently newer generation proteosome inhibitors, monoclonal antibodies
      and novel agents have been approved by FDA, which is undoubtedly increasing life
      expectancy of the patients. However, hematopoietic stem cell transplantation
      still remains the cornerstone of the treatment. In this chapter, we are
      discussing the autologous stem cell transplant, allogeneic stem cell transplant
      and total therapy trials with outcomes.

PMID- 27696267
TI  - Bone Disease in Multiple Myeloma.
AB  - Bone involvement represented by osteolytic bone disease (OBD) or osteopenia is
      one of the pathognomonic and defining characteristics of multiple myeloma (MM).
      Nearly 90 % of patients with MM develop osteolytic bone lesions, frequently
      complicated by skeletal-related events (SRE) such as severe bone pain,
      pathological fractures, vertebral collapse, hypercalcemia, and spinal cord
      compression. All of these not only result in a negative impact on quality of life
      but also adversely impact overall survival. OBD is a consequence of increased
      osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in
      altered bone remodeling. OC number and activity are increased in MM via cytokine
      deregulation within the bone marrow (BM) milieu, whereas negative regulators of
      OB differentiation suppress bone formation. Inhibition of osteolysis and
      stimulation of OB differentiation leads to reduced tumor growth in vivo.
      Therefore, novel agents targeting OBD are promising therapeutic strategies not
      only for the treatment of MM OBD but also for the treatment of MM. Several novel
      agents in addition to bisphosphonates are currently under investigation for their
      positive effect on bone remodeling via OC inhibition or OB stimulation. Future
      studies will look to combine or sequence all of these agents with the goal of not
      only alleviating morbidity from MM OBD but also capitalizing on the resultant
      antitumor activity.

PMID- 27696268
TI  - Immunoglobulin Light Chain Systemic Amyloidosis.
AB  - Immunoglobulin light chain amyloidosis (AL) is a rare, complex disease caused by
      misfolded free light chains produced by a usually small, indolent plasma cell
      clone. Effective treatments exist that can alter the natural history, provided
      that they are started before irreversible organ damage has occurred. The
      cornerstones of the management of AL amyloidosis are early diagnosis, accurate
      typing, appropriate risk-adapted therapy, tight follow-up, and effective
      supportive treatment. The suppression of the amyloidogenic light chains using the
      cardiac biomarkers as guide to choose chemotherapy is still the mainstay of
      therapy. There are exciting possibilities ahead, including the study of oral
      proteasome inhibitors, antibodies directed at plasma cell clone, and finally
      antibodies attacking the amyloid deposits are entering the clinic, offering
      unprecedented opportunities for radically improving the care of this disease.

PMID- 27696269
TI  - Waldenstrom Macroglobulinemia: Genomic Aberrations and Treatment.
AB  - Waldenstrom macroglobulinemia (WM) is a rare, indolent, and monoclonal
      immunoglobulin M-associated lymphoplasmacytic disorder with unique
      clinicopathologic characteristics. Over the past decade, remarkable progress has
      occurred on both the diagnostic and therapeutic fronts in WM. A deeper
      understanding of the disease biology emanates from the seminal discoveries of
      myeloid differentiation primary response 88 (MYD88) L265P somatic mutation in the
      vast majority of cases and C-X-C chemokine receptor, type 4, mutations in about a
      third of patients. Although WM remains an incurable malignancy, and the
      indications to initiate treatment are largely unchanged, the therapeutic
      armamentarium continues to expand. Acknowledging the paucity of high-level
      evidence from large randomized controlled trials, herein, we evaluate the genomic
      aberrations and provide a strategic framework for the management in the frontline
      as well as the relapsed/refractory settings of symptomatic WM.

PMID- 27696270
TI  - New technologies - new insights into the pathogenesis of hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which frequently
      accompanies acute or chronic liver disease. It is characterized by a variety of
      symptoms of different severity such as cognitive deficits and impaired motor
      functions. Currently, HE is seen as a consequence of a low grade cerebral oedema
      associated with the formation of cerebral oxidative stress and deranged cerebral
      oscillatory networks. However, the pathogenesis of HE is still incompletely
      understood as liver dysfunction triggers exceptionally complex metabolic
      derangements in the body which need to be investigated by appropriate
      technologies. This review summarizes technological approaches presented at the
      ISHEN conference 2014 in London which may help to gain new insights into the
      pathogenesis of HE. Dynamic in vivo 13C nuclear magnetic resonance spectroscopy
      was performed to analyse effects of chronic liver failure in rats on brain energy
      metabolism. By using a genomics approach, microRNA expression changes were
      identified in plasma of animals with acute liver failure which may be involved in
      interorgan interactions and which may serve as organ-specific biomarkers for
      tissue damage during acute liver failure. Genomics were also applied to analyse
      glutaminase gene polymorphisms in patients with liver cirrhosis indicating that
      haplotype-dependent glutaminase activity is an important pathogenic factor in HE.
      Metabonomics represents a promising approach to better understand HE, by
      capturing the systems level metabolic changes associated with disease in
      individuals, and enabling monitoring of metabolic phenotypes in real time, over a
      time course and in response to treatment, to better inform clinical decision
      making. Targeted fluxomics allow the determination of metabolic reaction rates
      thereby discriminating metabolite level changes in HE in terms of production,
      consumption and clearance.

PMID- 27696272
TI  - Interest in Collaborative, Practice-Based Research Networks in Pediatric Refugee
      Health Care.
AB  - Over the last decade, approximately 200,000 refugee children have resettled
      across the United States. This population is dispersed, resulting in limited
      data. Collaborative research networks, where clinicians across distinct practice
      sites work together to answer research questions, can improve the evidence base
      regarding clinical care. We distributed a web-based survey to pediatric refugee
      providers around North America to assess priorities, perceived barriers and
      benefits to collaborative research. We recruited 57 participants. Of respondents,
      89 % were interested in collaborative research, prioritizing: (1) access to
      health care (33 %), (2) mental health (24 %) and (3) nutrition/growth (24 %).
      Perceived benefits were "improving clinical practice" (98 %) and "raising
      awareness about the needs of pediatric refugees" (94 %). Perceived barriers were
      "too many other priorities" (89 %) and "lack of funding for data entry" (78 %).
      There is widespread interest in collaborative networks around pediatric refugee
      healthcare. A successful network will address barriers and emphasize priorities.

PMID- 27696271
TI  - The Role of Autophagy in the Maintenance of Stemness and Differentiation of
      Mesenchymal Stem Cells.
AB  - Regulated self-consumption, also known as autophagy, is an evolutionary conserved
      process that degrades cellular components by directing them to the lysosomal
      compartment of eukaryotic cells. As a major intracellular degradation and
      recycling pathway, autophagy is crucial for maintaining and remodeling cellular
      homeostasis during normal cellular and tissue development. Recent studies have
      demonstrated that autophagy is necessary for the maintenance of cellular stemness
      and for a number of differentiation processes, including the lineage
      determination of mesenchymal stem cells. These are multipotent progenitor cells
      with self-renewal capacities that can give rise to a subset of tissues and thus
      hold a consistent potential in regenerative medicine. Here, we review the current
      literature on the complex liaison between autophagy induced by various extra- or
      intracellular stimuli and the molecular targets that affect mesenchymal stem
      cells proliferation and differentiation.

PMID- 27696273
TI  - Screening for intermediate CGG alleles of FMR1 gene in male Iranian patients with
      Parkinsonism.
AB  - Male carriers of an expansion of CGG alleles (with 55-200 CGG repeats) in the
      FMR1 gene are affected with Fragile X-associated tremor/ataxia syndrome (FXTAS).
      On the other hand, individuals with Parkinson's disease (PD) or Parkinsonism
      spectrum disorders may have some clinical features that overlap with FXTAS. To
      investigate the possible association between PD and FMR1 expanded alleles, we
      screened a total of 154 male PD patients and 190 gender- and age-matched healthy
      control subjects from Iran. Eleven intermediate allele carriers (7.14 %) were
      detected among PD patients, compared with three carriers (1.57 %) among the
      controls (P = 0.01). No pre-mutation carriers were identified. Our results
      indicate that there is a potential association between FMR1 intermediate expanded
      alleles and PD.

PMID- 27696274
TI  - Early rehabilitation: benefits in patients with severe acquired brain injury.
AB  - Establish the best time to start rehabilitation by means of scientific evidence.
      Observational study in patients with a diagnosis of Severe Brain Injury who
      received intensive inpatient rehabilitation after acute care. 1470 subjects
      enrolled: 651 with Traumatic Brain Injury (TBI) and 819 with Non-TBI. Male gender
      was prevalent in the population study, but sex distribution was not different
      among groups, with a prevalence of male gender in both populations. This project
      involved 29 rehabilitation facilities for Severe ABI. The registry was an
      electronic database, remained active only during the period of data collection.
      The patients were divided into three different categories according to the time
      interval from brain injury to inpatient rehabilitation admission and demographic
      and clinical data were collected. Etiology, time interval from injury to
      inpatient rehabilitation, disability severity, the presence of tracheostomy at
      admission to the rehabilitation facility, rehabilitation length of stay and
      transfer back to acute care wards because of medical, surgical or neurosurgical
      complications. The interval from brain injury to rehabilitation facilities
      admission increases along with age, brain injury severity according to DRS
      scores, the presence of a tracheal tube and the percentage of transfers back to
      acute care wards from rehabilitation facilities, because of medical, surgical or
      neurosurgical complications. The better recovery and more positive outcomes,
      reported as resulting from early rehabilitation, may be due more to less severity
      of brain injury and fewer complications in the acute and post-acute phase than to
      when the rehabilitation starts.

PMID- 27696275
TI  - School Bullies' Intention to Change Behavior Following Teacher Interventions:
      Effects of Empathy Arousal, Condemning of Bullying, and Blaming of the
      Perpetrator.
AB  - This study examines how bullies' perceptions of how they were treated by a
      teacher (or other school personnel) during discussions aimed at putting an end to
      bullying influenced their intention to change their behavior. After each
      discussion, which took place as part of the implementation of an anti-bullying
      program, bullies anonymously reported the extent to which they felt that the
      teacher aroused their empathy for the victim, condemned their behavior, or blamed
      them. Half of the schools implementing the program were instructed to handle
      these discussions in a confrontational way-telling the bully that his behavior is
      not tolerated-while the other half were instructed to use a non-confronting
      approach. Schools were randomly assigned to one of the two approaches. A total of
      341 cases (188 in primary and 153 in secondary schools) handled in 28 Finnish
      schools were analyzed. Regression analyses showed that attempts at making bullies
      feel empathy for the victim and condemning their behavior both increased bullies'
      intention to stop. Blaming the bully had no significant effect. Bullies'
      intention to change was the lowest when both empathy-arousal and condemning
      behavior were low. The effects of empathy arousal were stronger when condemning
      the behavior was low (and vice versa), suggesting that teachers tackling bullying
      should make sure to use at least one of these strategies. When choosing not to
      raise the child's empathy, clear reprobation of the behavior is key.

PMID- 27696276
TI  - Risk factors for postoperative complications in robotic general surgery.
AB  - The feasibility and safety of robotically assisted procedures in general surgery
      have been reported from various groups worldwide. Because postoperative
      complications may lead to longer hospital stays and higher costs overall,
      analysis of risk factors for postoperative surgical complications in this subset
      of patients is clinically relevant. The goal of this study was to identify risk
      factors for postoperative morbidity after robotic surgical procedures in general
      surgery. We performed an observational monocentric retrospective study. All
      consecutive robotic surgical procedures from November 2001 to December 2013 were
      included. One thousand consecutive general surgery patients met the inclusion
      criteria. The mean overall postoperative morbidity and major postoperative
      morbidity (Clavien >III) rates were 20.4 and 6 %, respectively. This included a
      conversion rate of 4.4 %, reoperation rate of 4.5 %, and mortality rate of 0.2 %.
      Multivariate analysis showed that ASA score >3 [OR 1.7; 95 % CI (1.2-2.4)],
      hematocrit value <38 [OR 1.6; 95 % CI (1.1-2.2)], previous abdominal surgery [OR
      1.5; 95 % CI (1-2)], advanced dissection [OR 5.8; 95 % CI (3.1-10.6)], and
      multiquadrant surgery [OR 2.5; 95 % CI (1.7-3.8)] remained independent risk
      factors for overall postoperative morbidity. It also showed that advanced
      dissection [OR 4.4; 95 % CI (1.9-9.6)] and multiquadrant surgery [OR 4.4; 95 % CI
      (2.3-8.5)] remained independent risk factors for major postoperative morbidity
      (Clavien >III). This study identifies independent risk factors for postoperative
      overall and major morbidity in robotic general surgery. Because these factors
      independently impacted postoperative complications, we believe they could be
      taken into account in future studies comparing conventional versus robot-assisted
      laparoscopic procedures in general surgery.

PMID- 27696277
TI  - Anal metastasis from rectal adenocarcinoma.
AB  - The metastasis of rectal cancer to the anus is rare. Here, we report a case of
      advanced rectal cancer, which had a diffuse venous invasion with anal metastasis
      and multiple lymph node and liver metastases. The patient was a 72-year-old woman
      who complained of perianal pain and fresh blood in the stools for 6 months. She
      had neither history of fistula-in-ano nor anal surgery. Digital examination
      revealed a 2-cm tumor at the 7 o'clock position, and the barium enema and
      colonoscopy confirmed advanced rectal cancer. Abdominal computed tomography
      revealed thickness of the upper rectum wall, right inguinal lymph node of 10 mm
      and multiple liver metastases. Laparoscopically assisted anterior resection, anal
      tumor resection, and right inguinal lymph node resection were performed, and the
      histopathological examination of the resected primary and metastatic tumors
      confirmed similar findings of moderately differentiated adenocarcinoma,
      suggestive of metastasis of the rectal cancer to the anal region. In the next
      procedure, she had the liver lesions resected. This case suggested the importance
      of the careful examination of the anus during colonoscopy, or digital examination
      for the detection of anal metastasis.

PMID- 27696278
TI  - Why parametric measures are critical for understanding typical and atypical
      cognitive development.
AB  - Children's cognitive abilities improve significantly over childhood and
      adolescence. We know from behavioral research that core cognitive processes such
      as working memory and mental attention improve significantly across development.
      Functional magnetic resonance imaging (fMRI) allows for investigating the
      typically developing, living brain in action. In the last twenty years we have
      learned a great deal about brain correlates associated with how adults hold and
      manipulate information in mind, however, neurocognitive correlates across
      development remain inconsistent. We present developmental fMRI findings on
      cognitive processes such as working memory and mental attention and discuss
      methodological and theoretical issues in the assessment of cognitive limitations
      in the visual spatial and verbal domains. We also review data from typical and
      atypical development and emphasize the unique contribution parametric measures
      can make in understanding neurocognitive correlates of typical and atypical
      development.

PMID- 27696279
TI  - Diet and Complementary Medicine for Chronic Unexplained Nausea and Vomiting and
      Gastroparesis.
AB  - OPINION STATEMENT: Chronic nausea and vomiting, whether or not associated with
      gastroparesis, are among the most difficult symptoms to manage. Patients
      typically undergo extensive evaluation and empiric treatment often with
      suboptimal results. Conventional therapies may not produce adequate symptom
      relief or may cause unacceptable side effects. Thus, it is not surprising that
      patients report a negative impact on well-being, since the intermittent or
      constant occurrence of these symptoms are a source of anxiety as they impact
      social interactions and ability to work. Patients may seek complementary and
      alternative medicine (CAM), which may include acupuncture and herbal
      formulations, not only to manage nausea and vomiting, but also to remedy those
      symptoms associated with chronic illness, like insomnia and general fatigue. This
      chapter will review diet and different modalities of CAM to treat gastroparesis
      and chronic unexplained nausea and vomiting.

PMID- 27696281
TI  - Exposure Potential and Health Impacts of Indium and Gallium, Metals Critical to
      Emerging Electronics and Energy Technologies.
AB  - The rapid growth of new electronics and energy technologies requires the use of
      rare elements of the periodic table. For many of these elements, little is known
      about their environmental behavior or human health impacts. This is true for
      indium and gallium, two technology critical elements. Increased environmental
      concentrations of both indium and gallium create the potential for increased
      environmental exposure, though little is known about the extent of this exposure.
      Evidence is mounting that indium and gallium can have substantial toxicity,
      including in occupational settings where indium lung disease has been recognized
      as a potentially fatal disease caused by the inhalation of indium particles. This
      paper aims to review the basic chemistry, changing environmental concentrations,
      potential for human exposure, and known health effects of indium and gallium.

PMID- 27696282
TI  - Chronic NK lymphocytosis identified by a distinct immunophenotypic pattern.

PMID- 27696280
TI  - Is Urinary Cadmium a Biomarker of Long-term Exposure in Humans? A Review.
AB  - Cadmium is a naturally-occurring element, and humans are exposed from cigarettes,
      food, and industrial sources. Following exposure, cadmium accumulates in the
      kidney and is slowly released into the urine, usually proportionally to the
      levels found in the kidneys. Cadmium levels in a single spot urine sample have
      been considered indicative of long-term exposure to cadmium; however, such a
      potentially exceptional biomarker requires careful scrutiny. In this review, we
      report good to excellent temporal stability of urinary cadmium (intraclass
      correlation coefficient 0.66-0.81) regardless of spot urine or first morning void
      sampling. Factors such as changes in smoking habits and diseases characterized by
      increased excretion of proteins may produce short-term changes in urinary cadmium
      levels. We recommend that epidemiologists use this powerful biomarker in
      prospective studies stratified by smoking status, along with thoughtful
      consideration of additional factors that can influence renal physiology and
      cadmium excretion.

PMID- 27696283
TI  - A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in
      patients with refractory febrile neutropenia.
AB  - Invasive fungal infection (IFI) is a major life-threatening problem encountered
      by patients with hematological malignancies receiving intensive chemotherapy.
      Empirical antifungal agents are therefore important. Despite the availability of
      antifungal agents for such situations, the optimal agents and administration
      methods remain unclear. We conducted a prospective phase 2 study of empirical 1
      mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive
      chemotherapy for hematological malignancies. All enrolled patients were high-risk
      and had recurrent prolonged febrile neutropenia despite having received broad
      spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3
      %) achieved the primary endpoint of successful treatment, thus exceeding the
      predefined threshold success rate. No patients developed IFI. The treatment
      completion rate was 73.8 %, and only two cases ceased treatment because of
      adverse events. The most frequent events were reversible electrolyte
      abnormalities. We consider low-dose L-AMB to provide comparable efficacy and
      improved safety and cost-effectiveness when compared with other empirical
      antifungal therapies. Additional large-scale randomized studies are needed to
      determine the clinical usefulness of L-AMB relative to other empirical antifungal
      therapies.

PMID- 27696285
TI  - What is This Image? 2016: Image 3 Result.

PMID- 27696284
TI  - Osteoporosis and Periodontitis.
AB  - Osteoporosis and periodontitis are both diseases characterized by bone
      resorption. Osteoporosis features systemic degenerative bone loss that leads to
      loss of skeletal cancellous microstructure and subsequent fracture, whereas
      periodontitis involves local inflammatory bone loss, following an infectious
      breach of the alveolar cortical bone, and it may result in tooth loss. Most cross
      sectional studies have confirmed the association of osteoporosis and
      periodontitis primarily on radiographic measurements and to a lesser degree on
      clinical parameters. Multiple shared risk factors include age, genetics, hormonal
      change, smoking, as well as calcium and vitamin D deficiency. Both diseases could
      also be risk factors for each other and have a mutual impact that requires
      concomitant management. Suggested mechanisms underlying the linkage are
      disruption of the homeostasis concerning bone remodeling, hormonal balance, and
      inflammation resolution. A mutual interventional approach is emerging with
      complex treatment interactions. Prevention and management of both diseases
      require interdisciplinary approaches and warrants future well-controlled
      longitudinal and interventional studies for evidence-based clinical guidelines.

PMID- 27696286
TI  - Radiation dose optimization for the bolus tracking technique in abdominal
      computed tomography: usefulness of real-time iterative reconstruction for
      monitoring scan.
AB  - The purpose of this study was to optimize the monitoring dose, obtained using the
      conventional filtered back projection (FBP) method and iterative reconstruction
      algorithms, for the bolus tracking technique. A phantom study was performed to
      assess the effect of the scan start time in patients grouped according to
      different body weights. An oval torso phantom was used for simulating the time
      enhancement curve of the bolus tracking technique. To reproduce image noise
      levels in the two body weight groups, the phantom diameter was adjusted with a
      water-equivalent material. The tube currents were 10, 20, 30, and 50 mA. The
      monitoring scan was performed with the conventional FBP method and real-time
      adaptive iterative dose reduction by three-dimensional processing (AIDR 3D). The
      results at different doses were compared with those at 50 mA. The volume computed
      tomography dose index was 1.31, 2.65, 3.93, and 6.56 mGy at tube currents of 10,
      20, 30, and 50 mA, respectively. The scan start time, reconstructed using FBP,
      was significantly faster at 10 and 20 mA in group A (50-59 kg) and at 20 mA in
      group B (>=80 kg). The CT values in the region of interest could not be measured
      at 10 mA because of artifacts. With real-time AIDR 3D, both groups showed no
      significant differences between the measurements obtained at 30 or 20 mA and
      those obtained at 50 mA. Our study demonstrated that the real-time AIDR 3D
      algorithm improved the accuracy of the CT measurements with the bolus tracking
      technique.

PMID- 27696287
TI  - Molecular Dissection of Seedling Salinity Tolerance in Rice (Oryza sativa L.)
      Using a High-Density GBS-Based SNP Linkage Map.
AB  - BACKGROUND: Salinity is one of the many abiotic stresses limiting rice production
      worldwide. Several studies were conducted to identify quantitative trait loci
      (QTLs) for traits associated to salinity tolerance. However, due to large
      confidence interval for the position of QTLs, utility of reported QTLs and the
      associated markers has been limited in rice breeding programs. The main objective
      of this study is to construct a high-density rice genetic map for identification
      QTLs and candidate genes for salinity tolerance at seedling stage. RESULTS: We
      evaluated a population of 187 recombinant inbred lines (RILs) developed from a
      cross between Bengal and Pokkali for nine traits related to salinity tolerance. A
      total of 9303 SNP markers generated by genotyping-by-sequencing (GBS) were mapped
      to 2817 recombination points. The genetic map had a total map length of 1650 cM
      with an average resolution of 0.59 cM between markers. For nine traits, a total
      of 85 additive QTLs were identified, of which, 16 were large-effect QTLs and the
      rest were small-effect QTLs. The average interval size of QTL was about 132 kilo
      base pairs (Kb). Eleven of the 85 additive QTLs validated 14 reported QTLs for
      shoot potassium concentration, sodium-potassium ratio, salt injury score, plant
      height, and shoot dry weight. Epistatic QTL mapping identified several pairs of
      QTLs that significantly contributed to the variation of traits. The QTL for high
      shoot K+ concentration was mapped near the qSKC1 region. However, candidate genes
      within the QTL interval were a CC-NBS-LRR protein, three uncharacterized genes,
      and transposable elements. Additionally, many QTLs flanked small chromosomal
      intervals containing few candidate genes. Annotation of the genes located within
      QTL intervals indicated that ion transporters, osmotic regulators, transcription
      factors, and protein kinases may play essential role in various salt tolerance
      mechanisms. CONCLUSION: The saturation of SNP markers in our linkage map
      increased the resolution of QTL mapping. Our study offers new insights on
      salinity tolerance and presents useful candidate genes that will help in marker
      assisted gene pyramiding to develop salt tolerant rice varieties.

PMID- 27696288
TI  - Communities of endophytic microorganisms in different developmental stages from a
      local variety as well as transgenic and conventional isogenic hybrids of maize.
AB  - The diversity of endophytic microorganisms may change due to the genotype of the
      host plant and its phenological stage. In this study we evaluated the effect of
      phenological stage, transgenes and genetic composition of maize on endophytic
      bacterial and fungal communities. The maize populations were composed of a local
      variety named Rosado (RS) and three isogenic hybrids. One isogenic hybrid was not
      genetically modified (NGM). Another hybrid (Hx) contained the transgenes cry1F
      and pat (T1507 event), which provide resistance to insects of the order
      Lepidoptera and tolerance to the glufosinate-ammonium herbicide, respectively.
      The third hybrid (Hxrr) contained the transgene cp4 epsps (NK603 event) combined
      with the transgenes cry1F and pat (T1507 event), which allow tolerance to the
      Roundup Ready herbicide, besides the characteristics of Hx. Evaluation of the
      foliar tissue was done through PCR-DGGE analysis, with specific primers for
      bacteria and fungi within four phenological stages of maize. The endophytic
      bacteria were only clustered by phenological stages; the structure of the fungal
      community was clustered by maize genotypes in each phenological stage. The fungal
      community from the local variety RS was different from the three hybrids (NGM, Hx
      and Hxrr) within the four evaluated stages. In the reproductive stage, the fungal
      community from the two transgenic hybrids (Hx and Hxrr) were separated, and the
      Hxrr was different from NGM, in the two field experiments. This research study
      showed that the genetic composition of the maize populations, especially the
      presence of transgenes, is the determining factor for the changes detected in the
      endophytic fungal community of maize leaves.

PMID- 27696289
TI  - Optimization of substrate preparation for oyster mushroom (Pleurotus ostreatus)
      cultivation by studying different raw materials and substrate preparation
      conditions (composting: phases I and II).
AB  - In recent years, oyster mushroom (Pleurotus ostreatus) has become one of the most
      cultivated mushrooms in the world, mainly in Brazil. Among many factors involved
      in a mushroom production, substrate preparation is the most critical step, which
      can be influenced by composting management techniques. Looking forward to
      optimizing the substrate preparation process, were tested different composting
      conditions (7 and 14 days of composting with or without conditioning), potential
      raw materials (decumbens grass, brizantha grass and sugarcane straw) and nitrogen
      supplementation (with or without wheat bran) on oyster mushroom yield and
      biological efficiency (BE). The substrate composted for 7 days with conditioning
      showed higher yield and biological efficiency of mushroom (24.04 and 100.54 %,
      respectively). Substrates without conditioning (7 and 14 days of composting)
      showed smaller mushroom yield and biological efficiency. Among the raw materials
      tested, brizantha grass showed higher mushroom yield followed by decumbens grass,
      sugarcane straw and wheat straw (28.5, 24.32, 23.5 and 19.27 %, respectively).
      Brizantha grass also showed higher biological efficiency followed by sugarcane
      straw, decumbens grass and wheat straw (123.95, 103.70, 96.90 and 86.44 %,
      respectively). Supplementation with wheat bran improved yield and biological
      efficiency in all substrate formulations tested; thus, oyster mushroom yield and
      biological efficiency were influenced by substrate formulation (raw materials),
      supplementation and composting conditions.

PMID- 27696290
TI  - Years of Drinking but Not the Amount of Alcohol Intake Contribute to the
      Association Between Alcoholic Cerebellar Degeneration and Worse Cognitive
      Performance. A Population-Based Study.

PMID- 27696292
TI  - Erratum to: Clinical role of HER2 gene amplification and chromosome 17: a study
      on 154 IHC-equivocal cases of invasive breast carcinoma patients.

PMID- 27696291
TI  - MicroRNA-218 inhibits the proliferation, migration, and invasion and promotes
      apoptosis of gastric cancer cells by targeting LASP1.
AB  - The present study aims to investigate the effects of microRNA-218 (miR-218) on
      the proliferation, migration, invasion, and apoptosis of gastric cancer (GC)
      cells by targeting LIM and SH3 domain protein 1 (LASP1). The GC cells in the
      logarithmic phase were selected and divided into five groups: the blank group,
      negative control (NC) group, miR-218 inhibitors group, miR-218 inhibitors +
      siLASP1 group, and miR-218 mimics + siLASP1 group. The miR-218 expression in each
      group was also detected by qRT-PCR. The CCK8 assay, Transwell migration, and
      invasion assays and flow cytometry were performed to determine the effects of miR
      218 on cell proliferation, migration, invasion, and apoptosis of GC cells.
      Western blotting was conducted to measure LASP1 protein expression in GC cells
      after transfection. The qRT-PCR revealed that the transfection of miR-218 mimics
      could upregulate the miR-218 expression, and the transfection of miR-218
      inhibitors could downregulate the miR-218 expression in the GC cells. Compared
      with the blank and NC groups, the proliferation, migration, and invasion of GC
      cells were significantly reduced in the miR-218 mimics, miR-218 inhibitors +
      siLASP1, and miR-218 mimics + siLASP1 groups but enhanced in the miR-218
      inhibitors group. Similarly, compared with the blank and NC groups, the cell
      apoptosis rates in the miR-218 mimics, miR-218 inhibitors + siLASP1, and the miR
      218 mimics + siLASP1 groups were significantly increased, while the miR-218
      inhibitors group had a lower apoptosis rate. In conclusion, these results
      indicate that miR-218 could inhibit the proliferation, migration, and invasion
      and promote apoptosis of GC cells by downregulating LASP1 expression.

PMID- 27696293
TI  - Reversion-inducing cysteine-rich protein with Kazal motifs and its regulation by
      glycogen synthase kinase 3 signaling in oral cancer.
AB  - The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and
      glycogen synthase kinase (GSK3) are novel tumor suppressors, and emerging
      evidence has suggested their active role in oral cancer pathogenesis. In the
      present study, 112 human samples, including 55 fresh samples of 14 adjacent
      normal tissues, 25 noninvasive oral tumors, and 18 invasive tumors, were
      included. The messenger RNA (mRNA) expression, protein expression, and promoter
      methylation of the RECK gene, as well as the expression of GSK3beta,
      phospho/total beta-catenin, and c-myc, were measured by RT-PCR, bisulphate
      modification-PCR, immunohistochemistry, and Western blot analysis. Additionally,
      ectopic expression of in/active GSK3beta was performed in cell culture
      experiments. This study provided information on the progressive silencing of RECK
      gene expression at the protein and mRNA levels paralleled with promoter
      hypermethylation at various stages of oral tumor invasion. RECK expression and
      the hypermethylation of the RECK gene promoter were negatively and positively
      correlated with pS9GSK3beta/c-myc expression, respectively. Further, a negative
      trend of RECK protein expression with nuclear beta-catenin expression was
      observed. Induced expression of active GSK3beta reversed the RECK silencing in
      SCC9 cells. Collectively, our results demonstrated that the silencing of the RECK
      gene, possibly regulated by the GSK3beta pathway, is an important event in oral
      cancer invasion and this pathway could be exploited for therapeutic
      interventions.

PMID- 27696294
TI  - Hepatitis C virus promotes hepatocellular carcinogenesis by targeting TIPE2, a
      new regulator of DNA damage response.
AB  - Infection of hepatitis C virus (HCV) is associated with primary hepatocellular
      carcinoma (HCC). However, its underlying molecular mechanisms remain enigmatic.
      Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2), a new negative
      regulator of immunity, plays significant roles in modulating inflammation and
      tumorigenesis. We hypothesized that TIPE2 might be involved in the development of
      HCV-induced HCC. To test this hypothesis, the expression of TIPE2 was determined
      by Western blot in the tumor and pericarcinomatous tissues collected from ten HCV
      positive HCC patients; the interaction between TIPE2 and HCV-encoded non
      structural proteins was analyzed by immunoprecipitation and immunofluorescence
      assays, and tumorigenesis and its mechanisms were studied in cell models and nude
      mice. Our results demonstrated that the expression of TIPE2 was significantly
      reduced in HCC tissues compared to that in the paracarcinoma tissues. HCV-encoded
      non-structural protein NS5A could specifically interact with TIPE2 and induce its
      degradation. Downregulation of TIPE2 by shRNA in cell lines increased genomic DNA
      damage and promoted cell colony formation in vitro and tumorigenesis in nude
      mice. In contrast, overexpression of TIPE2 had an opposite effect. Downregulation
      of TIPE2 by NS5A is associated with genomic DNA instability and HCV-induced HCC
      development. Thus, TIPE2 may be a new therapeutic target for the treatment of HCV
      associated HCC.

PMID- 27696295
TI  - Serum microRNA-21 expression as a prognostic and therapeutic biomarker for breast
      cancer patients.
AB  - MiRNA-21 is recognized as the main active candidate and high expression in many
      solid tumors consequential cell proliferation, differentiation, apoptosis, and
      closely related to metastasis of disease. The study aimed to evaluate the serum
      miRNA-21 expression and therapy outcome in breast cancer patients and cell lines.
      Seventy-five histopathologically confirmed newly diagnosed breast cancer patients
      were included in the study; before and after therapy, patient's blood sample were
      collected and analyzed for serum microRNA-21 expression by quantitative real-time
      PCR. In patients, 8.9 mean fold increased microRNA-21 expression was observed
      compared to controls. Increased expression was found to be associated with
      advanced stage (11.72-fold), lymph node involvement (11.12-fold), and distant
      metastases (20.17-fold). After treatment significant decrease in miRNA-21
      expression was observed and found to be significant (p < 0.0001). Patients
      treated with neoadjuvant therapy had significant impact on miRNA-21 suppression
      and found to be significantly associated with different clinicopathological
      features of patients. Increased miRNA-21 expression was also found to be
      significantly associated with poor survival of breast cancer patients (p =
      0.002). MicroRNA-21 expression could be used as promising predictive indicators
      for breast cancer prognosis. MicroRNA-21 over-expression was associated with
      response to neoadjuvant therapy and may perhaps be considered as primary
      treatment choice.

PMID- 27696296
TI  - Periostin promotes the chemotherapy resistance to gemcitabine in pancreatic
      cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer-related deaths.
      The nucleoside analog gemcitabine has been the cornerstone of adjuvant
      chemotherapy in PDAC for decades. However, gemcitabine resistance develops within
      weeks of chemotherapy initiation, which might be intrinsic to cancer cells and
      influenced by tumor microenvironment. Recently, pancreatic stellate cells (PSCs)
      have greatly increased our attention on tumor microenvironment-mediated drug
      resistance. Periostin is exclusively overexpressed in PSCs and the stroma of PDAC
      creating a tumor-supportive microenvironment in the pancreas. However, whether
      periostin contributed to chemoresistance in PDAC remains unknown. Therefore, we
      focused on the role of periostin in PDAC by observing the effects of silencing
      this gene on gemcitabine resistance in vitro and in vivo aiming to explore the
      possible molecular mechanism. In this study, the pancreatic cancer cell (PCC)
      proliferation and apoptosis were assayed to investigate the sensitivity to
      gemcitabine after silencing periostin. We provide the evidence that periostin not
      only drives the carcinogenic process itself but also significantly associated
      with gemcitabine-induced apoptosis. These findings collectively indicated that
      periostin increases the chemoresistance to gemcitabine. Thus, targeting periostin
      might offer a new opportunity to overcome the gemcitabine resistance of PDAC.

PMID- 27696297
TI  - How the reference values for serum parathyroid hormone concentration are (or
      should be) established?
AB  - Well-validated reference values are necessary for a correct interpretation of a
      serum PTH concentration. Establishing PTH reference values needs recruiting a
      large reference population. Exclusion criteria for this population can be defined
      as any situation possibly inducing an increase or a decrease in PTH
      concentration. As recommended in the recent guidelines on the diagnosis and
      management of asymptomatic primary hyperparathyroidism, PTH reference values
      should be established in vitamin D-replete subjects with a normal renal function
      with possible stratification according to various factors such as age, gender,
      menopausal status, body mass index, and race. A consensus about analytical/pre
      analytical aspects of PTH measurement is also needed with special emphasis on the
      nature of the sample (plasma or serum), the time and the fasting/non-fasting
      status of the blood sample. Our opinion is that blood sample for PTH measurement
      should be obtained in the morning after an overnight fast. Furthermore, despite
      longer stability of the PTH molecule in EDTA plasma, we prefer serum as it allows
      to measure calcium, a prerequisite for a correct interpretation of a PTH
      concentration, on the same sample. Once a consensus is reached, we believe an
      important international multicentre work should be performed to recruit a very
      extensive reference population of apparently healthy vitamin D-replete subjects
      with a normal renal function in order to establish the PTH normative data. Due to
      the huge inter-method variability in PTH measurement, a sufficient quantity of
      blood sample should be obtained to allow measurement with as many PTH kits as
      possible.

PMID- 27696298
TI  - Timing of the negative effects of trastuzumab on cardiac mechanics after
      anthracycline chemotherapy.
AB  - Trastuzumab (TZB) has been shown to be extremely effective in breast cancer
      patients over-expressing HER-2, but careful cardiac monitoring is required when
      TZB is administered with anthracyclines, since the combination can increase its
      toxicity. Myocardial deformation indexes associated with speckle tracking
      echocardiography (STE) have proven to be very sensitive in identifying early
      myocardial dysfunction. An observational, prospective study was designed to
      assess TZB-induced cardiac damage using STE in patients with HER-2 positive
      breast cancer who had been sequentially treated with TZB following epirubicin
      (EPI). Conventional echocardiographic parameters and STE deformation indexes
      (longitudinal, radial, and circumferential strain/strain rate and apical
      rotation) were analyzed at baseline, after each EPI treatment, and 1 week after
      every other dose of TZB administration until 1 year follow up, in order to focus
      on the timing and extent of myocardial impairment. In the forty-five enrolled
      patients, a reduction in subendocardial function after EPI treatment was observed
      by a significant impairment of the global longitudinal strain/strain rate
      (GLS/SR), while a significant increase in the activity of the subepicardial
      fibers was highlighted by an increase in apical rotation. After the second TZB
      dose, a sudden reduction of the apical rotation was seen, together with
      circumferential and radial strain/SR. Most importantly, the extent to which the
      apical rotation increased and decreased was found to strictly correlate with the
      GLS reduction at follow up. We found that after EPI therapy, subendocardial
      function was impaired, even while a compensatory increase in apical rotation
      occurred. Following TZB treatment, we observed impairment in apical rotation,
      which seems to be the first sign of global LV dysfunction predicting GLS
      reduction found at the end of treatment.

PMID- 27696299
TI  - Treatment-Related Progressive Multifocal Leukoencephalopathy in Multiple
      Sclerosis: A Comprehensive Review of Current Evidence and Future Needs.
AB  - Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic
      infection of the central nervous system caused by the John Cunningham virus (JCV)
      that has been associated with therapeutic immunosuppression in patients with
      multiple sclerosis (MS). So far, more than 600 cases of PML have been reported in
      association with natalizumab administration. There have also been confirmed cases
      of PML in individuals who received fingolimod and dimethyl fumarate without
      previous natalizumab treatment. The new licensed disease-modifying therapies for
      MS carry the risk of immunosuppressant and so of JCV reactivation. Various
      factors have been identified with increased risk of developing PML, including a
      positive JCV serology, natalizumab administration for >2 years, and prior use of
      immunosuppressive agents. Clinicians can employ such tools for patients' risk
      stratification, but the incidence of PML among patients receiving natalizumab
      therapy has not changed. In this review we outline the current state of
      understanding of PML pathogenesis and patients' risk stratification. The
      landscape of MS is dramatically changing and knowledge of the side effects of the
      licensed therapies is imperative to enable optimal decision making.

PMID- 27696301
TI  - Systematical investigation of a combinative particle size reduction technology
      for production of resveratrol nanosuspensions.
AB  - Nanosizing is frequently used as formulation approach to increase the
      bioavailability of poorly water-soluble drugs. However, standard size reduction
      processes can be relatively time-consuming. It was found that the modification of
      the physical properties of a starting material by means of spray-drying can be
      used to improve the effectiveness of a subsequently performed high pressure
      homogenization. Such a process belongs to the combinative particle size reduction
      methods and is also referred to as H 42 process. Based on previous studies, it
      was hypothesized that the improved efficiency was a result of reduced
      crystallinity of the modified drug. The present study was conducted in order to
      asses this hypothesis in a systematical manner by applying design of experiment
      (DoE) principles. Resveratrol was selected as model compound for this study. It
      was processed by both standard high pressure homogenization and by a combinative
      particle size reduction process (the H42 process). An optimized
      resveratrol/surfactant ratio for the spray-dried intermediate was identified by
      using the response-surface methodology. The optimization led to a nanosuspension
      with a mean particle size of 192 nm, which is much smaller than the mean particle
      size of 569 nm when standard high pressure homogenization was used. Both
      predominately crystalline and predominately amorphous solids resulted from the
      spray-drying process. In contrast to the initial hypothesis, the smallest
      particle sizes were achieved by processing predominately crystalline intermediate
      with high pressure homogenization.

PMID- 27696302
TI  - Electrosprayed Janus Particles for Combined Photo-Chemotherapy.
AB  - This work is a proof of concept study establishing the potential of
      electrosprayed Janus particles for combined photodynamic therapy-chemotherapy.
      Sub-micron-sized particles of polyvinylpyrrolidone containing either an anti
      cancer drug (carmofur) or a photosensitiser (rose bengal; RB), and Janus
      particles containing both in separate compartments were prepared. The functional
      components were present in the amorphous form in all the particles, and infrared
      spectroscopy indicated that intermolecular interactions formed between the
      different species. In vitro drug release studies showed that both carmofur and RB
      were released at approximately the same rate, with dissolution complete after
      around 250 min. Cytotoxicity studies were undertaken on model human dermal
      fibroblasts (HDF) and lung cancer (A549) cells, and the influence of light on
      cell death explored. Formulations containing carmofur as the sole active
      ingredient were highly toxic to both cell lines, with or without a light
      treatment. The RB formulations were non-toxic to HDF when no light was applied,
      and with photo-treatment caused large amounts of cell death for both A549 and HDF
      cells. The Janus formulation containing both RB and carmofur was non-toxic to HDF
      without light, and only slightly toxic with the photo-treatment. In contrast, it
      was hugely toxic to A549 cells when light was applied. The Janus particles are
      thus highly selective for cancer cells, and it is hence proposed that such
      electrosprayed particles containing both a chemotherapeutic agent and
      photosensitiser have great potential in combined chemotherapy/photodynamic
      therapy.

PMID- 27696300
TI  - Risk-Benefit Profile of Direct-Acting Oral Anticoagulants in Established
      Therapeutic Indications: An Overview of Systematic Reviews and Observational
      Studies.
AB  - Since 2008, the direct-acting oral anticoagulants (DOACs) have expanded the
      therapeutic options of cardiovascular diseases with recognized clinical and
      epidemiological impact, such as non-valvular atrial fibrillation (NVAF) and
      venous thromboembolism (VTE), and also in the preventive setting of orthopedic
      surgical patients. The large body of evidence, not only from pivotal clinical
      trials but also from 'real-world' postmarketing observational findings (e.g.
      analytical epidemiological studies and registry data) gathered to date allow for
      a first attempt at verifying a posteriori whether or not the pharmacological
      advantages of the DOACs actually translate into therapeutic innovation, with
      relevant implications for clinicians, regulators and patients. This review aims
      to synthesize the risk-benefit profile of DOACs in the aforementioned
      consolidated indications through an 'evidence summary' approach gathering the
      existent evidence-based data, particularly systematic reviews with meta-analyses
      of randomized controlled trials, as well as observational studies, comparing
      DOACs with vitamin K antagonists. Clinical evidence will be discussed and
      compared with major international guidelines to identify whether an update is
      needed. Controversial clinically relevant safety issues will be also examined in
      order to highlight current challenges and unsettled questions (e.g. actual
      bleeding risk in susceptible populations). It is anticipated that the large
      number of publications on NVAF or VTE (44 systematic reviews with meta-analyses
      and 12 observational studies retained in our analysis) suggests the potential
      existence of overlapping studies and calls for common criteria to qualitatively
      and quantitatively assess discordances, thus guiding future research.

PMID- 27696304
TI  - Focus on Bioinformatics, Software, and MS-Based "Omics," Honoring Dr. Michael J.
      MacCoss, Recipient of the 2015 ASMS Biemann Medal.

PMID- 27696303
TI  - MALAT1 Long Non-coding RNA Expression in Thyroid Tissues: Analysis by In Situ
      Hybridization and Real-Time PCR.
AB  - Long non-coding RNAs (lncRNAs) are important for transcription and for epigenetic
      or posttranscriptional regulation of gene expression and may contribute to
      carcinogenesis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1),
      an lncRNA involved in the regulation of the cell cycle, cell proliferation, and
      cell migration, is known to be deregulated in multiple cancers. Here, we analyzed
      the expression of MALAT1 on 195 cases of benign and malignant thyroid neoplasms
      by using tissue microarrays for RNA in situ hybridization (ISH) and real-time
      PCR. MALAT1 is highly expressed in normal thyroid (NT) tissues and thyroid
      tumors, with increased expression during progression from NT to papillary thyroid
      carcinomas (PTCs) but is downregulated in poorly differentiated thyroid cancers
      (PDCs) and anaplastic thyroid carcinomas (ATCs) compared to NT. Induction of
      epithelial to mesenchymal transition (EMT) by transforming growth factor (TGF)
      beta in a PTC cell line (TPC1) led to increased MALAT1 expression, supporting a
      role for MALAT1 in EMT in thyroid tumors. This is the first ISH study of MALAT1
      expression in thyroid tissues. It also provides the first piece of evidence
      suggesting MALAT1 downregulation in certain thyroid malignancies. Our findings
      support the notion that ATCs may be molecularly distinct from low-grade thyroid
      malignancies and suggest that MALAT1 may function both as an oncogene and as a
      tumor suppressor in different types of thyroid tumors.

PMID- 27696305
TI  - Identifying the role of reactive oxygen species (ROSs) in Fusarium solani spores
      inactivation.
AB  - The inactivation mechanism of photocatalytic disinfectants on bacteria is well
      known. In contrast, the potential inactivation of fungal spores by visible-light
      induced photocatalysis has been recognized, but the inactivation mechanism is
      poorly understood. We hypothesize that photocatalytically generated reactive
      oxygen species (ROSs) are directly involved in this mechanism. To test this
      hypothesis, we identified the roles of ROSs in the inactivation of Fusarium
      solani spores. As the photocatalysts, we doped TiO2 with 3 typical dopants,
      forming Ag/TiO2, N/TiO2 and Er3+:YAlO3/TiO2. The Ag/TiO2 photocatalysis was
      dominated by H2O2, with the longest lifetime among the investigated ROSs. Ag/TiO2
      photocatalysis yielded almost 100 % inactivation efficiency and preserved the
      cell-wall shape of the spores, thus minimizing the biomolecule leakage.
      Er3+:YAlO3/TiO2 was dominated by h+ ROSs, yielding an inactivation efficiency of
      91 %; however, the severe leakage released large numbers of molecular bio
      products. Severe damage to the cell walls by the h+ species was confirmed in
      micrograph observations. Subsequent to cell wall breakage, the Er3+:YAlO3/TiO2
      nanoparticles entered the spore cells and directly oxidized the intracellular
      material. The N/TiO2 photocatalysis, with *O2- dominated ROSs, delivered
      intermediate performance. In conclusion, photocatalysts that generate H2O2
      dominated ROSs are most preferred for spore inactivation.

PMID- 27696306
TI  - Assessing the Potential Cost-Effectiveness of Microneedle Patches in Childhood
      Measles Vaccination Programs: The Case for Further Research and Development.
AB  - OBJECTIVE: Currently available measles vaccines are administered by subcutaneous
      injections and require reconstitution with a diluent and a cold chain, which is
      resource intensive and challenging to maintain. To overcome these challenges and
      potentially increase vaccination coverage, microneedle patches are being
      developed to deliver the measles vaccine. This study compares the cost
      effectiveness of using microneedle patches with traditional vaccine delivery by
      syringe-and-needle (subcutaneous vaccination) in children's measles vaccination
      programs. METHODS: We built a simple spreadsheet model to compute the vaccination
      costs for using microneedle patch and syringe-and-needle technologies. We assumed
      that microneedle vaccines will be, compared with current vaccines, more heat
      stable and require less expensive cool chains when used in the field. We used
      historical data on the incidence of measles among communities with low measles
      vaccination rates. RESULTS: The cost of microneedle vaccination was estimated at
      US$0.95 (range US$0.71-US$1.18) for the first dose, compared with US$1.65 (range
      US$1.24-US$2.06) for the first dose delivered by subcutaneous vaccination. At 95
      % vaccination coverage, microneedle patch vaccination was estimated to cost
      US$1.66 per measles case averted (range US$1.24-US$2.07) compared with an
      estimated cost of US$2.64 per case averted (range US$1.98-US$3.30) using
      subcutaneous vaccination. CONCLUSIONS: Use of microneedle patches may reduce
      costs; however, the cost-effectiveness of patches would depend on the vaccine
      recipients' acceptability and vaccine effectiveness of the patches relative to
      the existing conventional vaccine-delivery method. This study emphasizes the need
      to continue research and development of this vaccine-delivery method that could
      boost measles elimination efforts through improved access to vaccines and
      increased vaccination coverage.

PMID- 27696307
TI  - Optimal Transducer Level for Atrial and Pulmonary Arterial Pressure Measurement
      in Patients with Functional Single Ventricle.
AB  - This study aimed to investigate the optimal transducer level for accurate
      measurement of atrial and pulmonary arterial pressures in the supine position for
      patients with functional single ventricle. Contrast-enhanced chest computed
      tomographic images of 108 patients who underwent either the bidirectional
      cavopulmonary shunt (BCPS) placement or the Fontan procedure were reviewed.
      Vertical distances from the skin of the back to the uppermost levels of fluid in
      the single atrium or the pulmonary artery confluence and their ratios to the
      greatest anteroposterior (AP) diameter of the thoracic cage were determined. In
      patients who underwent BCPS, the ratios of the uppermost levels of blood in the
      atrium and pulmonary artery confluence to the greatest AP diameter of the thorax
      were 76.0 +/- 8.1 and 56.3 +/- 5.5 %, respectively. The distance (mm) between
      these two levels was calculated as 24.2 + 0.31 * age (years) (r 2 = 0.08, P <
      0.03). In patients who underwent the Fontan procedure, the ratios were 79.3 +/-
      10.0 and 58.3 +/- 5.8 %, respectively. The distance (mm) between these two levels
      was calculated as 31.1 + 0.44 * age (years) (r 2 = 0.05, P < 0.11). The optimal
      transducer levels for measuring atrial and pulmonary arterial pressures in the
      supine position are 75-80 and 55-60 % of the AP diameter of the thorax,
      respectively, in patients with functional single ventricle. We should consider
      the difference of the pressure when atrial and pulmonary arterial pressures were
      measured with the same level of transducers.

PMID- 27696308
TI  - MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac
      hypertrophy.
AB  - Mitogen-activated protein kinases (MAPKs) (ERK1/2, JNK, and p38) are upregulated
      in diabetic cardiomyopathy (DCM). Dual-specific phosphatase-1 (DUSP-1) has been
      reported to regulate the activity of MAPKs in cardiac hypertrophy; however, the
      role of DUSP-1 in regulating MAPKs activity in DCM is not known. MicroRNAs have
      been reported to regulate the expression of several genes in hypertrophied
      failing hearts. However, little is known about the microRNAs regulating DUSP-1
      expression in diabetes-related cardiac hypertrophy. In the present study, we
      investigated the role of DUSP-1 and miR-200c in diabetes-induced cardiac
      hypertrophy. DCM was induced in Wistar rats by low-dose Streptozotocin high-fat
      diet for 12 weeks. Cardiac expression of ERK, p-38, JNK, DUSP-1, miR-200c, and
      hypertrophy markers (ANP and beta-MHC) was studied in DCM in control rats and in
      high-glucose (HG)-treated rat neonatal cardiomyocytes. miR-200c inhibition was
      performed to validate DUSP-1 as target. A significant increase in phosphorylated
      ERK, p38, and JNK was observed in DCM model and in HG-treated cardiomyocytes (p <
      0.05). Expression of DUSP-1 was significantly decreased in diabetes group and in
      HG-treated cardiomyocytes (p < 0.05). Increased expression of miR-200c was
      observed in DCM model and in HG-treated cardiomyocytes (p < 0.05). Inhibition of
      miR-200c induces the expression of the DUSP-1 causing decreased expression of
      phosphorylated ERK, p38, and JNK and attenuated cardiomyocyte hypertrophy in HG
      treated cardiomyocytes. miR-200c plays a role in diabetes-associated cardiac
      hypertrophy by modulating expression of DUSP-1.

PMID- 27696309
TI  - Epidermal growth factor receptor targeting alters gene expression and restores
      the adhesion function of cancerous cells as measured by single cell force
      spectroscopy.
AB  - Loss of cell-cell adhesion function is a common characteristic of many human
      epithelial carcinomas that is frequently due to loss of E-cadherin expression. In
      cancer progression, loss of E-cadherin is associated with invasion and metastasis
      potential, hence restoration of its function may contribute to the metastasis
      inhibition. This study examined effect of Epidermal Growth Factor Receptor
      (EGFR/Her1) blockade on the E-cadherin expression, cellular adherence, and cell
      elasticity in two human epithelial cancer cell lines, MCF7 and A431. EGFR
      blocking agents as antibodies or small molecules target EGFR directly.
      Furthermore, due to intracellular signaling pathways they influence cell behavior
      and activities. The idea here is to investigate the effect of reduced activity of
      this signaling pathway using anti-EGFR Antibody (Cetuximab) and tyrosine kinase
      inhibitor (Lapatinib) on cell-cell adhesion and cell mechanical properties. Real
      Time PCR analysis demonstrated that treatment of cells with considered drugs
      increased the expression of E-cadherin gene among samples. The atomic force
      microscopy-based single cell force spectroscopy technique was used to measure
      adhesive force of cancerous cells. Results indicated that inhibition of EGFR
      activity elevated cell-cell adhesion force, accompanied by stiffening of the cell
      bodies. In summary, Cetuximab and Lapatinib have been found to mediate cell-cell
      adhesion by restoration of E-cadherin expression and function. Our data suggest
      possible therapeutic potential for inhibition of metastasis via the blockade of
      EGFR signaling.

PMID- 27696310
TI  - Chemoprotective and chemosensitizing properties of selenium nanoparticle (Nano
      Se) during adjuvant therapy with cyclophosphamide in tumor-bearing mice.
AB  - Cyclophosphamide (CP) is one of the widely used anticancer agents; however, it
      has serious deleterious effects on normal host cells due to its nonspecific
      action. The essential trace element Selenium (Se) is suggested to have
      chemopreventive and chemotherapeutic efficacy and currently used in
      pharmaceutical formulations. Previous report had shown Nano-Se could protect CP
      induced hepatotoxicity and genotoxicity in normal Swiss albino mice; however, its
      role in cancer management is still not clear. The aim of present study is to
      investigate the chemoprotective efficacy of Nano-Se against CP-induced toxicity
      as well as its chemoenhancing capability when used along with CP in Swiss albino
      mice against Ehrlich's ascites carcinoma (EAC) cells. CP was administered (25
      mg/kg b.w., i.p.) and Nano-Se was given (2 mg Se/kg b.w., p.o.) in concomitant
      and pretreatment schedule. Increase levels of serum hepatic marker, hepatic lipid
      peroxidation, DNA damage, and chromosomal aberration in CP-treated mice were
      significantly (P < 0.05) reversed by Nano-Se. The lowered status of various
      antioxidant enzymes in tumor-bearing mice after CP treatment was also effectively
      increased by Nano-Se. Administration of Nano-Se along with CP caused a
      significant reduction in tumor volume, packed cell volume, viable tumor cell
      count, and increased the survivability of the tumor-bearing hosts. The results
      suggest that Nano-Se exhibits significant antitumor and antioxidant effects in
      EAC-bearing mice. The potential for Nano-Se to ameliorate the CP-evoked toxicity
      as well as to improve the chemotherapeutic effect could have beneficial
      implications for patients undergoing chemotherapy with CP.

PMID- 27696311
TI  - Effectiveness of minimally invasive surgical procedures in the acceleration of
      tooth movement: a systematic review and meta-analysis.
AB  - OBJECTIVE: The objective of this study was to assess systematically the available
      scientific evidence relating the efficiency of minimally invasive surgical
      procedures in accelerating orthodontic tooth movement and the adverse effects
      associated with these procedures. METHODS: Electronic search of these databases
      CENTRAL, EMBASE, Scopus, PubMed, Web of Science, Google Scholar Beta, Trip,
      OpenGrey and PQDT OPEN was performed (last updated January 2016). The reference
      lists of the included studies were hand searched. Unpublished literature and
      ongoing studies were also checked electronically through ClinicalTrials.gov and
      (ICTRP). Randomized controlled trials (RCTs) with patients who received minimally
      invasive surgical procedures combined with fixed orthodontic appliances compared
      with conventional treatment were included. Cochrane's risk of bias tool was used
      to assess risk of bias. RESULTS: Four RCTs (61 patients) and nine ongoing
      protocols were included in this review. Only three RCTs were suitable for
      quantitative synthesis. Higher tooth movement rate was found with the minimally
      invasive surgical procedures by a weighted mean difference of 0.65 mm for 1 month
      of canine retraction (WMD = 0.65: 95 % CI (0.54, 0.76), p < 0.001) and by a
      weighted mean difference 1.41 mm for 2 months (WMD = 1.41: 95 % CI (0.81, 2.01),
      p < 0.001). No adverse effects associated with these procedures were reported.
      CONCLUSIONS: There is limited available evidence about the effectiveness of
      minimally invasive surgically accelerated orthodontics (MISAO). Although the
      current review indicated that MISAO can help in accelerating canine retraction,
      further research in this domain should be performed before it can be recommended
      in everyday clinical practice.

PMID- 27696313
TI  - ?

PMID- 27696312
TI  - Influence of maxillary posterior dentoalveolar discrepancy on angulation of
      maxillary molars in individuals with skeletal open bite.
AB  - BACKGROUND: The aim of this study was to determine the effect of the maxillary
      posterior dentoalveolar discrepancy (MPDD) on the angulation of maxillary molars
      in open bite subjects. METHODS: Pre-treatment lateral cephalograms of 90 young
      adults with skeletal open bite were examined. The sample initially included six
      groups categorized according to MPDD condition (present or absent) and sagittal
      skeletal facial growth patterns (classes I, II, or III). Then, the sample was
      separated into two groups according to MPDD (present = 50, absent = 40). When the
      eruption of the maxillary third molar was apparently blocked by the presence of
      an erupted second molar, a MPDD was considered. Maxillary molar angulation was
      measured. Independent T test was performed to determine differences between the
      groups considering MPDD condition. Principal component analysis (PCA) and
      multivariate analysis (MANCOVA) test were also developed. RESULTS: A decreased
      molar angulation was found in all groups with MPDD (overall p < 0.001, class I-p
      < 0.001, class II-p < 0.001, and class III-p < 0.05). The maxillary first and
      second molars angulations were lower between approximately 7 degrees  and 14
      degrees  in cases with posterior discrepancy. The PCA was used to reduce the
      number of initial cephalometric variables; thereafter, a MANCOVA test was
      applied. Significance was only found for MPDD (p < 0.001), APDI (p = 0.001), and
      ratio (A'6'/A'P') (p = 0.026) for maxillary first molar angulation and APDI (p =
      0.011) and MPDD (p < 0.001) for maxillary second molar angulation. CONCLUSIONS:
      The MPDD generates a major mesial displacement of the second and first molar
      roots with a concurrent simultaneous distal angulation of the associated crowns
      in individuals with skeletal open bite.

PMID- 27696314
TI  - [Lymphadenitis and systemic lupus erythematosus].
AB  - A 25-year-old Caucasian female patient presented with fever and cervical
      lymphadenopathy. Laboratory findings showed elevated signs of inflammation,
      elevated ANA titer and strongly positive anti-dsDNA antibodies. The
      histopathology of the lymph nodes revealed distinct features of Kikuchi-Fujimoto
      disease, a benign, self-limiting lymphadenopathy that typically affects young
      Asian females. In the literature a coincidental occurrence of Kikuchi-Fujimoto
      disease and systemic lupus erythematosus (SLE) is well documented. We
      hypothesized a simultaneous occurrence of both diseases because of the typical
      antibodies and arthralgia.

PMID- 27696315
TI  - Methylophaga and Hyphomicrobium can be used as target genera in monitoring saline
      water methanol-utilizing denitrification.
AB  - Which bacterial taxonomic groups can be used in monitoring saline water methanol
      utilizing denitrification and whether nitrate is transformed into N2 in the
      process are unclear. Therefore, methylotrophic bacterial communities of two
      efficiently functioning (nitrate/nitrite reduction was 63-96 %) tropical and cool
      seawater reactors at a public aquarium were investigated with clone library
      analysis and 454 pyrosequencing of the 16S rRNA genes. Transformation of nitrate
      into N2 was confirmed using 15N labeling in incubation of carrier material from
      the tropical reactor. Combining the data with previous study results,
      Methylophaga and Hyphomicrobium were determined to be suitable target genera for
      monitoring the function of saline water methanol-fed denitrification systems.
      However, monitoring was not possible at the single species level. Interestingly,
      potential nitrate-reducing methylotrophs within Filomicrobium and closely related
      Fil I and Fil II clusters were detected in the reactors suggesting that they also
      contributed to methylotrophic denitrification in the saline environment.

PMID- 27696316
TI  - [Regional geriatric care concept in the District of Lippe : Structural effects
      and network formation in the case management-based model project].
AB  - BACKGROUND: Regional planning of healthcare requires special consideration for
      the complex needs of elderly, multimorbid people living in a domestic
      environment. In the District of Lippe, a hospital (Klinikum Lippe) and network of
      ambulatory care physicians (Arztenetz Lippe) developed and tested a geriatric
      care network based on case management for geriatric patients living in a domestic
      environment. MATERIAL AND METHODS: The establishment of the geriatric care
      network (e.g. promoting networking acceptance and implementation) was formatively
      evaluated, e. g. with qualitative methods. Data were acquired by guideline-based
      interviews with experts and analyzed by qualitative content analysis according to
      Mayring. RESULTS: Structural effects included forming a cross-sectoral and
      interdisciplinary network for a functioning care network and a geriatric care
      pathway. The practical work of case managers (CM) is essential for communication
      with patients, family members and care providers as well as integrating providers
      into the network. A critical factor was working together with general
      practitioners and the close cooperation with the hospital's department of
      geriatric. The quality of care is improved because of exchange of information
      between sectors and continuity in the course of care. CONCLUSION: In the District
      of Lippe the quality of care was improved and structures of care were integrated
      by the network according to the needs of the target group. The integrative
      perspective was achieved in particular by the geriatric care pathway and
      integration of providers into the communication and care process; however, the
      scope of this care model could not be extended into routine care due to the rigid
      and subdivided health care system.

PMID- 27696317
TI  - Left Atrial Appendage Closure for Stroke Prevention in Atrial Fibrillation.
AB  - PURPOSE OF REVIEW: Anticoagulant therapy effectively reduces the incidence of
      stroke in patients with atrial fibrillation (AF) but is underutilized and
      frequently contraindicated. The left atrial appendage (LAA) is the primary site
      of thrombus formation in AF patients. Surgical and percutaneous appendage closure
      has been evaluated as a site-specific therapy to reduce systemic thromboembolism.
      RECENT FINDINGS: We will review LAA closure techniques, examine recent outcome
      data, and discuss the indications for, and potential complications of, each
      approach. Randomized data examining surgical LAA closure and epicardial closure
      with the LARIAT device are lacking. High quality, randomized data supports the
      efficacy of the WATCHMAN device for stroke prevention in patients with AF.

PMID- 27696319
TI  - Coronary Computed Tomography Angiography for Screening in Patients with Diabetes:
      Can Enhanced Detection of Subclinical Coronary Atherosclerosis Improve Outcome?
AB  - PURPOSE OF REVIEW: It is well known that there is a very high risk of
      cardiovascular complications among diabetic patients. In spite of all efforts at
      aggressive control of diabetes and its complications, the incidence of
      cardiovascular morbidity and mortality remains high, including in patients with
      no prior symptoms, underscoring a possible advantage for appropriate screening of
      asymptomatic patients for the presence of obstructive coronary artery disease
      (CAD). In this article, we sought primarily to review the results of studies
      designed to evaluate a possible role of coronary computed tomography angiography
      (CCTA) in the screening of asymptomatic diabetic patients for possible
      obstructive CAD. RECENT FINDINGS: Our review of current literature indicates that
      there is still no method of CAD screening identified that has been shown to
      reduce the cardiovascular risk of asymptomatic diabetic patients. Therefore, the
      utility and value of screening for CAD in asymptomatic diabetic patients remains
      controversial. CCTA screening has shown promise and has been demonstrated to
      predict future risk, but as yet has not demonstrated improvement in the outcomes
      of these high-risk patients. At our present state of knowledge, aggressive risk
      factor reduction appears to be the most important primary prevention strategy for
      all asymptomatic high-risk diabetic patients. However, there remains a great need
      for better and more sensitive and specific screening methods, as well as more
      effective treatments that may allow us to more accurately target diabetic
      patients who really are at high risk. Further large randomized and well
      controlled clinical trials may be necessary to determine whether screening for
      CAD can reduce cardiovascular event rates in patients with diabetes.

PMID- 27696320
TI  - Effect of Gelatin-Stabilized Copper Nanoparticles on Catalytic Reduction of
      Methylene Blue.
AB  - The synthesis of copper nanoparticles was carried out with gelatin as a
      stabilizer by reducing CuSO4.5H2O ions using hydrazine. Ascorbic acid and aqueous
      NaOH were also used as an antioxidant and pH controller, respectively. The
      effects of NaOH, hydrazine, and concentration of gelatin as stabilizer were
      studied. The synthesized copper nanoparticles were characterized by UV-vis
      spectroscopy, XRD, zeta potential measurements, FTIR, EDX, FESEM, and TEM. The
      formation of CuNPs@Gelatin is initially confirmed by UV-vis spectroscopic
      analysis with the characteristic band at 583 nm. XRD and TEM reports revealed
      that CuNPs@Gelatin (0.75 wt.%) is highly crystalline and spherical in shape with
      optimum average size of 4.21 +/- 0.95 nm. FTIR studies indicated the presence of
      amide group on the surface of the CuNPs indicating the stability of CuNPs which
      is further supported by zeta potential measurements with the negative optimum
      value of -37.90 +/- 0.6 mV. The CuNPs@G4 showed a good catalytic activity against
      methylene blue (MB) reduction using NaBH4 as a reducing agent in an aqueous
      solution. The best enhanced properties of CuNPs@G4 were found for the 0.75 wt.%
      gelatin concentration. Thermodynamic parameters (DeltaH and DeltaS) indicate that
      under the studied temperature, the reduction of MB by CuNPs@G4 is not feasible
      and had endothermic in nature.

PMID- 27696318
TI  - Statin Adherence: Does Gender Matter?
AB  - PURPOSE OF REVIEW: Cardiovascular disease (CVD) continues to be the leading cause
      of death for men and women in the USA. Statins have contributed significantly to
      noted declines in cardiovascular-related mortality in the last decade; however,
      the benefit of statins is inequitable across genders. Women continue to be less
      likely to take statins and to meet target LDL goals than men. As a possible
      contributing factor to this disparity, we explore the evidence for gender-based
      differences in provision of, and adherence to statins. RECENT FINDINGS: Compared
      with men, women are less likely to adhere to statins. Potential reasons for this
      gender difference in use of statins can be observed across all phases of
      adherence including both intentional and unintentional non-adherence. Notable
      gender-specific contributing factors for statin non-adherence include decreased
      provider and patient awareness of CVD risk among women, higher risk of statin
      intolerance among women, and competing demands associated with family caregiving
      responsibilities. Similar to limitations in the broader CVD literature, there is
      inadequate inclusion of gender-specific analyses in statin-related trials. Gender
      based disparities in statin adherence can be linked to both provider level,
      psychosocial, and medication intolerance factors. Interventions designed to
      improve statin adherence should take gender-specific challenges into
      consideration such as women being older at the time of increased CVD risk, higher
      rates of statin intolerance, and potentially greater caregiving responsibilities.

PMID- 27696321
TI  - G4-Tetra DNA Duplex Induce Lung Cancer Cell Apoptosis in A549 Cells.
AB  - The specific DNA is typically impermeable to the plasma membrane due to its
      natural characters, but DNA tetra structures (DTNs) can be readily uptake by
      cells in the absence of transfection agents, providing a new strategy to deliver
      DNA drugs. In this research, the delivery efficiency of tetrahedral DNA
      nanostructures was measured on adenocarcinomic human alveolar basal epithelial
      (A549) cells via delivering AS1411 (G4). The DNA tetra-AS1411 complex was rapidly
      and abundantly uptake by A549 cells, and the induced apoptosis was enhanced.
      Furthermore, biodistribution in mouse proved the rapid clearance from non
      targeted organs in vivo. This study improved the understanding of potential
      function in DNA-based drug delivery and proved that DTNs-AS1411 could be
      potentially useful for the treatment of lung cancer.

PMID- 27696322
TI  - Fabrication of NaYF4:Yb,Er Nanoprobes for Cell Imaging Directly by Using the
      Method of Hydrion Rivalry Aided by Ultrasonic.
AB  - A novel method of fabricating water-soluble bio-probes with ultra-small size such
      as NaYF4:Yb,Er (18 nm), NaGdF4:Yb,Er (8 nm), CaF2:Yb,Er (10 nm), PbS (7 nm), and
      ZnS (12 nm) has been developed to provide for the solubility switch of
      nanoparticles from oil-soluble to water-soluble in terms of hydrion rivalry aided
      by ultrasonic. Using NaYF4:Yb,Er (18 nm) as an example, we evaluate the
      properties of as-prepared water-soluble nanoparticles (NPs) by using
      thermogravimetric analyses (TGA), Fourier transform infrared spectroscopy (FTIR),
      zeta potential (zeta) testing, and 1H nuclear magnetic resonance (1HNMR). The
      measured zeta value shows that the newly prepared hydrophilic NaYF4:Yb,Er NPs are
      the positively charged particles. Acting as reactive electrophilic moiety, the
      freshly prepared hydrophilic NaYF4:Yb,Er NPs have carried out the coupling with
      amino acids and fluorescence labeling and imaging of HeLa cells directly.
      Experiments indicate that the method of hydrion rivalry aided by ultrasonic
      provides a simple and novel opportunity to transform hydrophobic NPs into
      hydrophilic NPs with good reactivity, which can be imaging some specific
      biological targets directly.

PMID- 27696323
TI  - Synthesis of Ultrathin WS2 Nanosheets and Their Tribological Properties as
      Lubricant Additives.
AB  - In this paper, ultrathin WS2 nanosheets with thickness of about 5 nm were
      successfully prepared by a facile solid phase reaction method. The as-synthesized
      samples were characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), and transmission electron microscopy (TEM). On the basis of
      experimental results obtained under different reaction durations, a possible
      formation mechanism of WS2 nanosheets is proposed. The tribological performance
      of ultrathin WS2 nanosheets as additives in the 500SN base oil was tested by an
      UMT-2 ball-on-disc tribotester, and the worn surface of the steel disc was
      investigated by a non-contact optical profile testing instrument and SEM. The
      results showed that the friction coefficient and anti-wear property of base oil
      can be improved strikingly by adding ultrathin WS2 nanosheets. Especially, when
      the concentration of WS2 nanosheets was 1.0 wt.%, the corresponding lubricating
      oil exhibited the best tribological properties. Moreover, according to the
      investigation of the wear scar, an anti-friction and anti-wear mechanism is
      proposed. It is believed that the reduction of friction and wear must come from
      the addition of ultrathin WS2 nanosheets which can penetrate and enter the
      friction interface and form a continuous tribofilm on the rubbing face.

PMID- 27696324
TI  - Neighborhood Deprivation during Early Childhood and Conduct Problems in Middle
      Childhood: Mediation by Aggressive Response Generation.
AB  - The tremendous negative impact of conduct problems to the individual and society
      has provided the impetus for identifying risk factors, particularly in early
      childhood. Exposure to neighborhood deprivation in early childhood is a robust
      predictor of conduct problems in middle childhood. Efforts to identify and test
      mediating mechanisms by which neighborhood deprivation confers increased risk for
      behavioral problems have predominantly focused on peer relationships and
      community-level social processes. Less attention has been dedicated to potential
      cognitive mediators of this relationship, such as aggressive response generation,
      which refers to the tendency to generate aggressive solutions to ambiguous social
      stimuli with negative outcomes. In this study, we examined aggressive response
      generation, a salient component of social information processing, as a mediating
      process linking neighborhood deprivation to later conduct problems at age 10.5.
      Participants (N = 731; 50.5 % male) were drawn from a multisite randomized
      prevention trial that includes an ethnically diverse and low-income sample of
      male and female children and their primary caregivers followed prospectively from
      toddlerhood to middle childhood. Results indicated that aggressive response
      generation partially mediated the relationship between neighborhood deprivation
      and parent- and teacher-report of conduct problems, but not youth-report. Results
      suggest that the detrimental effects of neighborhood deprivation on youth
      adjustment may occur by altering the manner in which children process social
      information.

PMID- 27696325
TI  - What is new in idiopathic clubfoot?
AB  - Idiopathic clubfoot has a tremendous worldwide prevalence. If left untreated, the
      deformity has severely disabling effects on mobility and quality of life. Given
      its prevalence and significance, numerous studies are published on this condition
      every year. In this article, we attempt to highlight important themes and
      findings of studies published on idiopathic clubfoot over the past 3 years.

PMID- 27696326
TI  - TLR4 and TLR21 expression, MIF, IFN-beta, MD-2, CD14 activation, and sIgA
      production in chickens administered with EFAL41 strain challenged with
      Campylobacter jejuni.
AB  - The protective effect of Enterococcus faecium EFAL41 on chicken's caecum in
      relation to the TLR (TLR4 and TLR21) activation and production of luminal IgA
      challenged with Campylobacter jejuni CCM6191 was assessed. The activation of MIF,
      IFN-beta, MD-2 and CD14 was followed-up after bacterial infection. Day-old chicks
      (40) were divided into four groups (n = 10): control (C), E. faecium AL41
      (EFAL41), C. jejuni (CJ) and combined E. faecium AL41+C. jejuni (EFAL41+CJ).
      Relative mRNA expression of TLR4, TLR21 and CD14 was upregulated in the probiotic
      strain and infected (combined) group on day 4 and 7 post infection (p.i.). The
      caecal relative MD-2 mRNA expression was upregulated on day 4 p.i. in the
      EFAL41+CJ and CJ groups. MIF and IFN-beta reached the highest levels in the
      combined groups on day 7 p.i. The concentration of the sIgA in intestinal flush
      was upregulated in EFAL41+CJ group on day 4 p.i. The results demonstrated that E.
      faecium EFAL41 probiotic strain can modulate the TLRs expression and modify the
      activation of MIF, IFN-beta, MD-2 and CD14 molecules in the chickens caecum
      challenged with C. jejuni CCM 6191. The counts of EFAL41 were sufficient and
      high, similarly the counts of enterococci in both, caecum and faeces but without
      reduction of Campylobacter counts.

PMID- 27696328
TI  - Determinants of Voluntary National Health Insurance Drop-Out in Eastern Sudan.
AB  - BACKGROUND: Low enrolment and high drop-out rates are common problems in
      voluntary health insurance schemes. Yet, most studies in this research area focus
      on community-based health insurance and enrolment, rather than drop-out.
      OBJECTIVE: This study examines what causes informal sector families not to renew
      their voluntary National Health Insurance Fund (NHIF) health insurance membership
      in Eastern Sudan. METHODS: Primary data from about 600 informal sector households
      that dropped out or remained insured, collected through a household survey
      conducted in March 2014, were used. Logistic regressions were employed to examine
      what determines drop-out of the voluntary NHIF scheme. RESULTS: The logistic
      regression results are consistent with the existing literature and confirm the
      importance of household head, household and community characteristics. Notably,
      worse family health status and higher health care utilization decrease the
      probability of drop-out, which requires further analysis as it may indicate the
      problem of adverse selection and insufficient risk management. Most importantly,
      the results consistently show that household heads who are satisfied with health
      services and those who understand the main features of the voluntary NHIF scheme
      are less likely to drop out. Also, 30 % of drop-out households hold a social
      support card and reported that the social support scheme is the main reason for
      not renewing their voluntary NHIF health insurance membership as they qualify for
      sponsored NHIF health insurance membership. CONCLUSIONS: This study shows that
      satisfaction with health services and knowledge of the health insurance scheme
      are important factors explaining drop-out of a national health insurance
      programme. The results suggest that education and information campaigns should be
      developed further to raise understanding of the NHIF voluntary scheme. In
      addition, information systems and coordination between the main agencies should
      be strengthened to reduce administrative costs and ensure policy coherence.

PMID- 27696327
TI  - Genetic trends for live weight traits reflect breeding strategies in registered
      Charolais Farms in Mexico.
AB  - Genetic trends are commonly used to verify genetic improvement; however, there
      are few reports on beef cattle in Mexico. Data from 1998 to 2013 from four
      Charolais bull breeding farms were examined to verify the genetic responses to
      different breeding management and selection criteria. Analysis included the
      comparison of regression lines of breeding values for birth (BW), weaning (WW)
      and yearling weights (YW), and maternal weaning weight (MWW) on the year of birth
      of the animals. Results revealed differential genetic progress for BW and YW and
      indicated that the overall analysis may have diluted the perception of genetic
      progress from the farmer's point of view. The use of breeding values as a tool
      for selection is effective to achieve genetic progress, even in negatively
      correlated traits, such as birth weight and yearling weight.

PMID- 27696329
TI  - Sustained Depolarization of the Resting Membrane Potential Regulates Muscle
      Progenitor Cell Growth and Maintains Stem Cell Properties In Vitro.
AB  - It is important to maintain the myogenic properties of muscle progenitor cells
      (MPCs) during in vitro expansion for stem cell therapies and tissue engineering
      applications. Controlling cell fate for biomedical interventions will require
      insight on all aspects that influence cellular properties. The resting membrane
      potential (Vmem) has proven to be a key parameter involved in cell proliferation,
      migration and differentiation. This current work is focused on elucidating the
      impact of sustained depolarization on MPC growth and differentiation in vitro.
      Cultures were treated with either potassium gluconate or the sodium-potassium
      pump blocker ouabain and evaluated for proliferation, DNA content using propidum
      iodide staining, and differentiation. Cell proliferation measurements showed a
      modest stimulatory effect at certain concentration ranges for each agent, but
      higher concentrations of potassium gluconate strongly inhibited growth in a dose
      dependent manner. Cell cycle analysis with flow cytometry demonstrated an
      increase in the number of cells in S phase, but increasing concentrations of
      potassium gluconate arrested cells at G1. Immunostaining, Western blot analysis
      and light microscopy revealed that potassium gluconate exposure delayed cell
      fusion and maintained a higher population of cells expressing the muscle stem
      cell marker Pax7. The impairment on cell fusion was transient and myotube
      formation recovered after the treatments were removed. Taken together, this work
      suggests that transmembrane voltage gradients can be used as a powerful regulator
      of MPC properties in vitro. Examination of how these physiological parameters
      modulate cell behavior will reveal a new set of tools that can be capitalized on
      in tissue engineering and regenerative medicine.

PMID- 27696330
TI  - DNA sensor cGAS-mediated immune recognition.
AB  - The host takes use of pattern recognition receptors (PRRs) to defend against
      pathogen invasion or cellular damage. Among microorganism-associated molecular
      patterns detected by host PRRs, nucleic acids derived from bacteria or viruses
      are tightly supervised, providing a fundamental mechanism of host defense.
      Pathogenic DNAs are supposed to be detected by DNA sensors that induce the
      activation of NFkappaB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed
      in innate immune cells and is a key sensor of invading DNAs in several cell
      types. cGAS binds to DNA, followed by a conformational change that allows the
      synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from
      adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of
      STING that can activate IRF3 and subsequent type I interferon production. Here we
      describe recent progresses in DNA sensors especially cGAS in the innate immune
      responses against pathogenic DNAs.

PMID- 27696331
TI  - TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast
      cancer cell senescence.
AB  - Human telomerase reverse transcriptase (hTERT) plays a central role in telomere
      lengthening for continuous cell proliferation, but it remains unclear how
      extracellular cues regulate telomerase lengthening of telomeres. Here we report
      that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene
      repression in a BMPRII receptor- and Smad3-dependent manner in human breast
      cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in
      short telomeres, cell senescence and apoptosis. Mutation of the BMPRII receptor,
      but not TGFbRII, ACTRIIA or ACTRIIB receptor, inhibits BMP7-induced repression of
      the hTERT gene promoter activity, leading to increased telomerase activity,
      lengthened telomeres and continued cell proliferation. Expression of hTERT
      prevents BMP7-induced breast cancer cell senescence and apoptosis. Thus, our data
      suggest that BMP7 induces breast cancer cell aging by a mechanism involving
      BMPRII receptor- and Smad3-mediated repression of the hTERT gene.

PMID- 27696332
TI  - A novel constitutive model for passive right ventricular myocardium: evidence for
      myofiber-collagen fiber mechanical coupling.
AB  - The function of right ventricle (RV) is recognized to play a key role in the
      development of many cardiopulmonary disorders, such as pulmonary arterial
      hypertension (PAH). Given the strong link between tissue structure and mechanical
      behavior, there remains a need for a myocardial constitutive model that
      accurately accounts for right ventricular myocardium architecture. Moreover, most
      available myocardial constitutive models approach myocardium at the length scale
      of mean fiber orientation and do not explicitly account for different fibrous
      constituents and possible interactions among them. In the present work, we
      developed a fiber-level constitutive model for the passive mechanical behavior of
      the right ventricular free wall (RVFW). The model explicitly separates the
      mechanical contributions of myofiber and collagen fiber ensembles, and accounts
      for the mechanical interactions between them. To obtain model parameters for the
      healthy passive RVFW, the model was informed by transmural orientation
      distribution measurements of myo- and collagen fibers and was fit to the
      mechanical testing data, where both sets of data were obtained from recent
      experimental studies on non-contractile, but viable, murine RVFW specimens.
      Results supported the hypothesis that in the low-strain regime, the behavior of
      the RVFW is governed by myofiber response alone, which does not demonstrate any
      coupling between different myofiber ensembles. At higher strains, the collagen
      fibers and their interactions with myofibers begin to gradually contribute and
      dominate the behavior as recruitment proceeds. Due to the use of viable
      myocardial tissue, the contribution of myofibers was significant at all strains
      with the predicted tensile modulus of [Formula: see text]32 kPa. This was in
      contrast to earlier reports (Horowitz et al. 1988) where the contribution of
      myofibers was found to be insignificant. Also, we found that the interaction
      between myo- and collagen fibers was greatest under equibiaxial strain, with its
      contribution to the total stress not exceeding 20 %. The present model can be
      applied to organ-level computational models of right ventricular dysfunction for
      efficient diagnosis and evaluation of pulmonary hypertension disorder.

PMID- 27696333
TI  - Soluble Epoxide Hydrolase Inhibitor Suppresses the Expression of Triggering
      Receptor Expressed on Myeloid Cells-1 by Inhibiting NF-kB Activation in Murine
      Macrophage.
AB  - Triggering receptors expressed on myeloid cell-1 (TREM-1) is a
      superimmunoglobulin receptor expressed on myeloid cells. TREM-1 amplifies the
      inflammatory response. Epoxyeicosatrienoic acids (EETs), the metabolites of
      arachidonic acid derived from the cytochrome P450 enzyme, have anti-inflammatory
      properties. However, the effects of EETs on TREM-1 expression under inflammatory
      stimulation remain unclear. Therefore, inhibition of soluble epoxide hydrolase
      (sEH) with a highly selective inhibitor [1-trifluoromethoxyphenyl-3-(1
      propionylpiperidin-4-yl) urea, TPPU] was used to stabilize EETs. LPS was
      intratracheally injected into mice to induce pulmonary inflammation, after TPPU
      treatment for 3 h. Histological examination showed TPPU treatment-alleviated LPS
      induced pulmonary inflammation. TPPU decreased TREM-1 expression, but not DAP12
      or MyD88 expression. Murine peritoneal macrophages were challenged with LPS in
      vitro. We found that TPPU reduced LPS-induced TREM-1 expression in a dose
      dependent manner, but not DAP12 or MyD88 expression. TPPU also decreased
      downstream signal from TREM-1, reducing pro-inflammatory cytokine TNF-alpha and
      IL-1beta mRNA expression. Furthermore, TPPU treatment inhibited IkB degradation
      in vivo and in vitro. Our results indicate that the inhibition of sEH suppresses
      LPS-induced TREM-1 expression and inflammation via inhibiting NF-kB activation in
      murine macrophage.

PMID- 27696335
TI  - Feasibility of rapid measurement of Rivaroxaban plasma levels in patients with
      acute stroke.
AB  - Plasma levels of Rivaroxaban (RivLev) might be useful to guide therapeutic
      decisions in patients with acute stroke under Rivaroxaban. A prerequisite for the
      potential clinical usefulness is their rapid availability in emergency
      situations. Single-center explorative analysis from the Novel-Oral-Anticoagulants
      in-Stroke-Patients-registry (NOACISP, cinicaltrials.gov:NCT02353585). We included
      consecutive patients with acute ischemic or hemorrhagic stroke under Rivaroxaban
      (last intake <48 h) in which RivLev determined by an automated anti-factor Xa
      based chromogenic assay (Hyphen-Biomed, France) are available. Primary endpoint
      was the turnaround time (TAT), defined as time from registration of the blood
      sample in the lab to first result published. Furthermore, we studied, whether TAT
      is influenced by (1) on- and off-hour-measurements and (2) early versus later
      patient arrival (cut-off: 270 min after symptom onset). Thirty-eight patients met
      the eligibility criteria (mean age 77 years, 44 % female). TAT was 34 min (IQR 29
      65 min). TATs were similar for on- (n = 14; median 34 min; IQR 30-56 min) and off
      hours-TATs (n = 24; median 35 min; IQR 29-75 min) as well as for early (n = 16;
      median 33 min; IQR 30-40 min) and late patient arrival (n = 22, median 34 min,
      IQR 28-58 min; all nonsignificant.). Taking into account RivLev in the decision
      process about the use of intravenous thrombolysis, three patients received
      intravenous thrombolysis on an individualized basis, none of them with bleeding
      complications. Emergency measurement of RivLev among patients with acute stroke
      is available within a median of 34 min and therefore feasible for ED use. Due to
      the rapid availability, further research to evaluate the role of RivLev in order
      to guide acute treatment decisions is warranted.

PMID- 27696336
TI  - Study on the Composition of Biogenic Iron-Containing Materials Obtained Under
      Cultivation of the Leptothrix sp. on Different Media.
AB  - The biogenic iron oxide/hydroxide materials possess useful combination of
      physicochemical properties and are considered for application in various areas.
      Their production does not require special investments because these compounds are
      formed during cultivation of neurophilic iron bacteria. Bacteria from genus
      Leptothrix develop intensively in the Sphaerotilus-Leptothrix group of bacteria
      isolation medium and feeding media of Fedorov and Lieske. These media are
      different in their composition which determined the present study as an attempt
      to clear up the reasons that define the differences in the composition of the
      laboratory-obtained biomasses and the natural biomass finds. FTIRS, Mossbauer
      spectroscopy, and XRD were used in the research. Comparative analysis showed that
      the biomass and control samples contain iron compounds (alpha-FeOOH, gamma-FeOOH,
      beta-FeOOH, gamma-Fe2O3) in different ratios. The biomass samples were enriched
      in oxyhydroxides of higher dispersion. Organic residuals of bacterial origin,
      SO4, CO3, and PO4 groups were registered in the biogenic materials.

PMID- 27696337
TI  - The Psycho-Neurology of Cross-Species Affective/Social Neuroscience:
      Understanding Animal Affective States as a Guide to Development of Novel
      Psychiatric Treatments.
AB  - During the past half century of research with preclinical animal models,
      affective neuroscience has helped identify and illuminate the functional
      neuroanatomies and neurochemistries of seven primary process, i.e., genetically
      provided emotional systems of mammalian brains. All are subcortically localized,
      allowing animal models to guide the needed behavioral and neuroscientific
      analyses at levels of detail that cannot be achieved through human research,
      including modern brain imaging. They consist of the following neuronal processes:
      SEEKING/Enthusiasm, RAGE/Anger, FEAR/Anxiety, sexual LUST/Passion, maternal
      CARE/Nurturance, separation-distress PANIC/Grief and PLAY/Social Joy. Several of
      these systems figure heavily in social bonding. I will focus here especially on
      the genesis of depression. Its genesis is significantly influenced by (i)
      sustained overactivity of the separation-distress PANIC system reflecting severed
      social bonds and the excessive "psychological pain" of loneliness that can, if
      sustained, lead to a downward cascade known as psychological despair, and (ii)
      the despair phase that follows the acute PANIC response, which is characterized
      by abnormally low activity of the SEEKING, the so-called brain reward networks,
      leading to amotivational states that characterize depression. Depressive affect
      is promoted by such brain affective mechanisms of social attachments and social
      loss as well as diminished arousability of the SEEKING system, leading to chronic
      dysphoria. To understand why depression feels so bad, we must understand the
      neural mechanisms that mediate such social feelings.

PMID- 27696334
TI  - Interleukin-35: a Potential Therapeutic Agent for Autoimmune Diseases.
AB  - Autoimmune diseases contain a large number of pathologies characterized by
      various factors that contribute to a breakdown in self-tolerance. Cytokine
      mediated immunity plays an essential role in the pathogenesis of varieties of
      autoimmune diseases. Recent studies reveal that interleukin-35 (IL-35), a newly
      identified cytokine of IL-12 family, is implicated in the pathogenesis of
      autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid
      arthritis (RA), systemic sclerosis (SSc), etc. In this review, we will discuss
      the biological features of IL-35 and summarize recent advances in the role of IL
      35 in the development and pathogenesis of autoimmune diseases; the discoveries
      gained from these findings might translate into future therapies for these
      diseases.

PMID- 27696338
TI  - Influence of IGF1, TGFbeta1, bFGF and G-CSF/M-CSF on the mRNA levels of selected
      matrix proteins, cytokines, metalloproteinase 3 and TIMP1 in rat synovial
      membrane cells.
AB  - INTRODUCTION: We have previously observed that rat synovial membranes incubated
      in medium containing cartilage interstitial fluid (CIF) responded by changes in
      the expression of hyaluronan synthases (HAS1 and HAS2), collagen type I,
      versican, aggrecan, lubricin, matrix metalloproteinases 2 and 3 (MMP2 and MMP3),
      tissue inhibitors of metalloproteinases (TIMP1, 2 and 3), transforming growth
      factor beta1 (TGFbeta1), tumor necrosis factor (TNF), interleukin (IL) 1beta and
      IL-6. The aim of the study was to evaluate the influence of particular cytokines
      found in CIF on the gene expression of extracellular matrix (ECM) proteins in
      synovial membrane cells. MATERIAL AND METHODS: Synovial membranes (SMs) were
      removed from the knee joints of inbred, male Lewis rats and incubated with
      insulin-like growth factor 1 (IGF1), TGFbeta1, basic fibroblast growth factor
      (bFGF) and granulocyte- macrophage colony-stimulating factors (G-CSF and M-CSF),
      either individually or in the combinations TGFbeta1/IGF1, TGFbeta1/IGF1/bFGF or G
      CSF/M-CSF. Next, total RNA was isolated and the studied genes' expression was
      evaluated by real-time PCR. RESULTS: TGFbeta1/IGF1 stimulated expression of HAS1,
      lubricin, collagen type I, aggrecan and TGFbeta1, inhibited expression of MMP3
      and TNF and had no effect on TIMP1 and IL-6 mRNA levels. TGFbeta1/IGF1/bFGF
      stimulated the expression of HAS1, lubricin and TGFbeta1 genes, inhibited the
      expression of TNF and had no effect of the expression of collagen 1, aggrecan,
      MMP3, TIMP1 and IL-6 genes. G-CSF/M-CSF stimulated the expression of aggrecan.
      TGFbeta1, bFGF, and IGF1 applied individually exerted inhibitory effect on the
      expression of lubricin. TGFbeta1 and bFGF inhibited expression of MMP3 and bFGF
      inhibited also the expression of aggrecan and TNF. CONCLUSIONS: The response of
      the studied genes represents a resultant activity of all major cell types
      building the synovial membrane, i.e. highly specialized synovial fibroblasts,
      macrophages, epithelial cells and adipocytes. The results of our study can
      improve understanding of synovial membrane responses to the intraarticular
      injections of platelet-rich plasma (PRP) used for the treatment of joint
      ailments, since PRP contains factors which are also present in CIF.

PMID- 27696339
TI  - Effects of sugammadex vs. pyridostigmine-glycopyrrolate on post-operative nausea
      and vomiting: propensity score matching.
AB  - BACKGROUND: Sugammadex is a new agent that reverses neuromuscular blockade by
      aminosteroid neuromuscular blocker. This retrospective study compared the effects
      of sugammadex on post-operative nausea and vomiting (PONV) with those of a
      pyridostigmine-glycopyrrolate mixture. METHODS: We reviewed the electronic
      medical records of 7179 patients who had received fentanyl-based, intravenous,
      patient-controlled analgesia (IV-PCA) at Chung-Ang University Hospital between
      January 1, 2010 and December 31, 2015. We categorized the patients into two
      groups on the basis of the type of reversal agent to neuromuscular blockade that
      was used: a traditional reversal agent (pyridostigmine-glycopyrrolate mixture;
      Group R; n = 7059) and sugammadex (Group S; n = 120). The propensity score
      matching method was then used to select 408 subjects in Group R and 115 subjects
      in Group S; on the basis of their covariates, these subjects were then matched
      with a counterpart in the other group. RESULTS: After propensity score matching,
      the two groups were well balanced with respect to all baseline covariates. In
      Group S, the numeric rating scale of nausea on day 0, as well as the number of
      patients who vomited on day 0, was lower than that in group R. Furthermore, Group
      S used fewer rescue antiemetics on day 0 and had a higher complete response on
      day 0. CONCLUSION: Sugammadex might be more beneficial for PONV compared to
      pyridostigmine-glycopyrrolate mixture for patients who have received opioid-based
      IV-PCA.

PMID- 27696340
TI  - Maternal and fetal characteristics affect discrepancies between pregnancy-dating
      methods: a population-based cross-sectional register study.
AB  - INTRODUCTION: Gestational age is estimated by ultrasound using fetal size as a
      proxy for age, although variance in early growth affects reliability. The aim of
      this study was to identify characteristics associated with discrepancies between
      last menstrual period-based (EDD-LMP) and ultrasound-based (EDD-US) estimated
      delivery dates. MATERIAL AND METHODS: We identified all singleton births (n = 1
      201 679) recorded in the Swedish Medical Birth Register in 1995-2010, to assess
      the association between maternal/fetal characteristics and large negative and
      large positive discrepancies (EDD-LMP earlier than EDD-US and 10th percentile in
      the discrepancy distribution vs. EDD-LMP later than EDD-US and 90th percentile).
      Analyses were adjusted for age, parity, height, body mass index, smoking, and
      employment status. RESULTS: Women with a body mass index >40 kg/m2 had the
      highest odds for large negative discrepancies (-9 to -20 days) [odds ratio (OR)
      2.16, 95% CI 2.01-2.33]. Other factors associated with large negative
      discrepancies were: diabetes, young maternal age, multiparity, body mass index
      between 30 and 39.9 kg/m2 or <18.5 kg/m2 , a history of gestational diabetes,
      female fetus, shorter stature (<-1 SD), a history of preeclampsia, smoking or
      snuff use, and unemployment. Large positive discrepancies (+4 to +20 days) were
      associated with male fetus (OR 1.80, 95% CI 1.77-1.83), age >=30 years,
      multiparity, not living with a partner, taller stature (>+1 SD), and
      unemployment. CONCLUSIONS: Several maternal and fetal characteristics were
      associated with discrepancies between dating methods. Systematic associations of
      discrepancies with maternal height, fetal sex, and partly obesity, may reflect an
      influence on the precision of the ultrasound estimate due to variance in early
      growth.

PMID- 27696341
TI  - Veterans Affairs Geriatric Scholars Program: Enhancing Existing Primary Care
      Clinician Skills in Caring for Older Veterans.
AB  - The Veterans Affairs Geriatric Scholars Program (GSP) is a continuing
      professional development program to integrate geriatrics into the clinical
      practices of primary care providers and select associated health professions that
      support primary care teams. GSP uses a blended program educational format, and
      the minimal requirements are to attend an intensive course in geriatrics,
      participate in an interactive workshop on quality improvement (QI), and initiate
      a local QI project to demonstrate application of new knowledge to benefit older
      veterans. Using a retrospective post/pre survey design, the effect of GSP on
      clinical practices and behaviors and variation of that effect on clinicians
      working in rural and nonrural settings were evaluated. Significant improvement
      was found in the frequency of using evidence-based brief standardized
      assessments, clinical decision-making, and standards of care. Significant
      subgroup differences were observed in peer-to-peer information sharing between
      rural and nonrural clinicians. Overall, 77% of the sample reported greater job
      satisfaction after participating in GSP. The program is a successful model for
      advancing postgraduate education in geriatrics and a model that might be
      replicated to increase access to quality health care, particularly in rural
      areas.

PMID- 27696342
TI  - Volunteering Is Associated with Lower Risk of Cognitive Impairment.
AB  - OBJECTIVES: To examine whether psychosocial factors that can be a target for
      interventions, such as volunteering, are associated with risk of cognitive
      impairment. DESIGN: Health and Retirement Study (HRS) data from 1998 to 2012, a
      nationally representative longitudinal panel survey of older adults assessed
      every 2 years, were used. SETTING: The HRS interviews participants aged 50 and
      older across the contiguous United States. PARTICIPANTS: Individuals aged 60 and
      older in 1998 (N = 13,262). MEASUREMENTS: Personal interviews were conducted with
      respondents to assess presence of cognitive impairment, measured using a
      composite across cognitive measures. RESULTS: Volunteering at the initial
      assessment and volunteering regularly over time independently decreased the risk
      of cognitive impairment over 14 years, and these findings were maintained
      independent of known risk factors for cognitive impairment. Greater risk of onset
      of cognitive impairment was associated with being older, being female, being
      nonwhite, having fewer years of education, and reporting more depressive
      symptoms. CONCLUSION: Consistent civic engagement in old age is associated with
      lower risk of cognitive impairment and provides impetus for interventions to
      protect against the onset of cognitive impairment. Given the increasing number of
      baby boomers entering old age, the findings support the public health benefits of
      volunteering and the potential role of geriatricians, who can promote
      volunteering by incorporating "prescriptions to volunteer" into their patient
      care.

PMID- 27696343
TI  - Low degree of satisfactory individual pain relief in post-operative pain trials.
AB  - BACKGROUND: The majority of clinical trials regarding post-operative pain
      treatment focuses on the average analgesic efficacy, rather than on efficacy in
      individual patients. It has been argued, that in acute pain trials, the
      underlying distributions are often skewed, which makes the average unfit as the
      only way to measure efficacy. Consequently, dichotomised, individual responder
      analyses using a predefined 'favourable' response, e.g. Visual Analogue Scale
      (VAS) pain scores <= 30, have recently been suggested as a more clinical relevant
      outcome. METHODS: We re-analysed data from 16 randomised controlled trials of
      post-operative pain treatment and from meta-analyses of a systematic review
      regarding hip arthroplasty. The predefined success criterion was that at least
      80% of patients in active treatment groups should obtain VAS < 30 at 6 and 24 h
      post-operatively. RESULTS: In the analysis of data from the randomised controlled
      trials, we found that at 6 h post-operatively, 50% (95% CI: 31-69) of patients
      allocated to active treatment reached the success criterion for pain at rest and
      14% (95% CI: 5-34) for pain during mobilisation. At 24 h post-operatively, 60%
      (95% CI: 38-78) of patients allocated to active treatment reached the success
      criterion for pain at rest, and 15% (95% CI: 5-36) for pain during mobilisation.
      Similar results were found for trials from the meta-analyses. CONCLUSION: Our
      results indicate that for conventional, explanatory trials of post-operative
      pain, individual patient's achievement of a favourable response to analgesic
      treatment is rather low. Future pragmatic clinical trials should focus on both
      average pain levels and individual responder analyses in order to promote
      effective pain treatment at the individually patient level.

PMID- 27696344
TI  - Velamentous or marginal cord insertion and the risk of spontaneous preterm birth,
      prelabor rupture of the membranes, and anomalous cord length, a population-based
      study.
AB  - INTRODUCTION: Anomalous cord insertion is associated with increased risk of
      adverse maternal and perinatal outcome. Our aim was to study whether anomalous
      cord insertion is associated with prelabor rupture of membranes (PROM), preterm
      PROM (pPROM), long or short umbilical cord, and time trend of spontaneous preterm
      birth (SPTB) and anomalous cord insertion. MATERIAL AND METHODS: A population
      based register study using data from the Medical Birth Register of Norway
      including all singleton births (gestational age >16 weeks and <45 weeks) during
      1999-2013 (n = 860 465) to calculate odds ratios (ORs) for PROM, pPROM, SPTB, and
      cord length (>95th or <5th centile) according to the cord insertion site by
      logistic regression with adjustment for possible confounders. We also assessed
      time trends of SPTB and anomalous cord insertion. RESULTS: Velamentous insertion
      of the cord was associated with an increased risk of PROM (OR 1.6, 95% CI 1.5
      1.7), pPROM (OR 2.7, 95% CI 2.4-3.0), SPTB (OR 2.0, 95% CI 1.9-2.2), and a short
      cord (OR 1.7, 95% CI 1.5-1.8). Marginal insertion was to a lesser extent
      associated with these complications. Occurrences of SPTB and anomalous insertion
      declined. The decline in SPTB persisted after including an interaction term
      between anomalous insertion and time. CONCLUSIONS: Velamentous and, to a lesser
      extent, marginal cord insertions were associated with increased risk of PROM,
      pPROM, SPTB, and short cord. This suggests a common pathogenesis behind altered
      function of the membranes, cord, and placenta. The decline in SPTB could not be
      explained by the reduction in the occurrence of anomalous cord insertion.

PMID- 27696345
TI  - The productive cellulase binding capacity of cellulosic substrates.
AB  - Cellulosic biomass is the most promising feedstock for renewable biofuel
      production; however, the mechanisms of the heterogeneous cellulose
      saccharification reaction are still unsolved. As cellulases need to bind isolated
      molecules of cellulose at the surface of insoluble cellulose fibrils or larger
      aggregated cellulose structures in order to hydrolyze glycosidic bonds, the
      "accessibility of cellulose to cellulases" is considered to be a reaction
      limiting property of cellulose. We have defined the accessibility of cellulose to
      cellulases as the productive binding capacity of cellulose, that is, the
      concentration of productive binding sites on cellulose that are accessible for
      binding and hydrolysis by cellulases. Productive cellulase binding to cellulose
      results in hydrolysis and can be quantified by measuring hydrolysis rates. In
      this study, we measured the productive Trichoderma reesei Cel7A (TrCel7A) binding
      capacity of five cellulosic substrates from different sources and processing
      histories. Swollen filter paper and bacterial cellulose had higher productive
      binding capacities of ~6 umol/g while filter paper, microcrystalline cellulose,
      and algal cellulose had lower productive binding capacities of ~3 umol/g.
      Swelling and regenerating filter paper using phosphoric acid increased the
      initial accessibility of the reducing ends to TrCel7A from 4 to 6 umol/g.
      Moreover, this increase in initial productive binding capacity accounted in large
      part for the difference in the overall digestibility between filter paper and
      swollen filter paper. We further demonstrated that an understanding of how the
      productive binding capacity declines over the course of the hydrolysis reaction
      has the potential to predict overall saccharification time courses. Biotechnol.
      Bioeng. 2017;114: 533-542. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696346
TI  - The effectiveness of the levonorgestrel intrauterine system in obese women with
      heavy menstrual bleeding.
AB  - INTRODUCTION: To evaluate the effectiveness of the levonorgestrel intrauterine
      system (LNG-IUS) in obese women with heavy menstrual bleeding in Counties Manukau
      Auckland area, New Zealand. METHODS: Prospective observational study in a
      tertiary teaching hospital. Twenty women with heavy menstrual bleeding (HMB) who
      agreed to treatment with the LNG-IUS and had a body mass index (BMI) of >30 kg/m2
      were recruited between May and December 2014. The women completed two validated
      tools (Menstrual Impact Questionnaire and the Pictorial Bleeding Assessment
      Chart) at recruitment, 6 and 12 months follow-up. Demographic, medical and
      laboratory variables were obtained from the relevant CMH databases. Data on side
      effects and satisfaction were obtained from the women at 12 months. RESULTS: The
      median age (range) and BMI of the 20 women were 40.5 years (27-52 years) and 40.6
      kg/m2 (30-68), respectively. Three LNG-IUS were removed due to infection and pain
      and these women were subsequently booked for a hysterectomy. The reduction in
      menstrual loss was estimated at 19.7% per month (95% CI (12.5%, 26.2%); P <
      0.001), which translates to 73.2% per period of 6 months (95% CI (55.3%, 83.9%))
      and 92.8% per period of 12 months (95% CI (80.0%, 97.4%)). The six items in the
      quality of life measure improved significantly in 14 women but only 12 women were
      satisfied with the treatment. CONCLUSION: The LNG-IUS was an effective treatment
      for 67% of obese women with heavy menstrual bleeding over a 12-month period, as
      assessed by the reduction in menstrual bleeding and the improvement in the
      quality of life measures.

PMID- 27696347
TI  - Lateral enamel growth in human incisors from Catalhoyuk in Turkey.
AB  - OBJECTIVES: Whereas the differences in lateral enamel growth between fossil and
      modern populations have been well documented in recent years, few studies report
      on the variability in perikymata counts and distribution between modern human
      populations. There is a need for information on modern human populations from a
      wide range of geographical regions and archaeological populations to determine
      whether existing patterns are representative. The aim of this paper is to
      document enamel surface microstructures in human teeth from a previously unknown
      region and time period comprehensively. MATERIALS AND METHODS: Perikymata counts
      and distribution are assessed in a large sample of relatively unworn permanent
      incisors from the mid-Holocene site of Catalhoyuk in Turkey. RESULTS: All four
      incisor types exhibit total perikymata counts that are intermediate between
      values for modern samples from northern Europe and South Africa. The perikymata
      distribution followed the modern human pattern of a marked decrease in spacing in
      the cervical half of the crown. DISCUSSION: The existence of regional differences
      in perikymata number and distribution demonstrates the importance of documenting
      enamel microstructures in a wider range of modern human populations, both
      geographically and chronologically.

PMID- 27696348
TI  - Silk scaffolds connected with different naturally occurring biomaterials for
      prostate cancer cell cultivation in 3D.
AB  - In the present work, different biopolymer blend scaffolds based on the silk
      protein fibroin from Bombyx mori (BM) were prepared via freeze-drying method. The
      chemical, structural, and mechanical properties of the three dimensional (3D)
      porous silk fibroin (SF) composite scaffolds of gelatin, collagen, and chitosan
      as well as SF from Antheraea pernyi (AP) and the recombinant spider silk protein
      spidroin (SSP1) have been systematically investigated, followed by cell culture
      experiments with epithelial prostate cancer cells (LNCaP) up to 14 days. Compared
      to the pure SF scaffold of BM, the blend scaffolds differ in porous morphology,
      elasticity, swelling behavior, and biochemical composition. The new composite
      scaffold with SSP1 showed an increased swelling degree and soft tissue like
      elastic properties. Whereas, in vitro cultivation of LNCaP cells demonstrated an
      increased growth behavior and spheroid formation within chitosan blended
      scaffolds based on its remarkable porosity, which supports nutrient supply
      matrix. Results of this study suggest that silk fibroin matrices are sufficient
      and certain SF composite scaffolds even improve 3D cell cultivation for prostate
      cancer research compared to matrices based on pure biomaterials or synthetic
      polymers.

PMID- 27696349
TI  - Introducing Cochrane Global Ageing: towards a new era of evidence.

PMID- 27696350
TI  - Effect of Geriatric-Specific Trauma Triage Criteria on Outcomes in Injured Older
      Adults: A Statewide Retrospective Cohort Study.
AB  - OBJECTIVES: To evaluate the effect on outcomes of the Ohio Department of Public
      Safety statewide geriatric triage criteria, established in 2009 for emergency
      medical services (EMS) to use for injured individuals aged 70 and older. DESIGN:
      Retrospective cohort study of the Ohio Trauma Registry. SETTING: All hospitals in
      Ohio. PARTICIPANTS: Individuals aged 70 and older in the Ohio Trauma Registry
      from January 2006 through December 2011, 3 years before and 3 years after
      criteria adoption (N = 34,499). MEASUREMENTS: Primary outcomes were in-hospital
      mortality and discharge to home. Criteria effects were assessed using chi-square
      tests, multivariable logistic regression, interrupted time series plots, and
      multivariable segmented regression models. RESULTS: After geriatric criteria were
      adopted, the proportion of older adults qualifying for trauma center transport
      increased from 44% to 58%, but EMS transport rates did not change (44% vs 45%).
      There was no difference in unadjusted mortality (7.1% vs 6.6%) (P = .10). In
      adjusted analyses, subjects with an injury severity score (ISS) less than 10 had
      lower mortality after adoption (3.0% vs 2.5%) (odds ratio (OR) = 0.81, 95%
      confidence interval (CI) = 0.70-0.95, P = .01). Discharge to home increased after
      adoption in the adjusted analysis (OR = 1.06, 95% CI = 1.01-1.11, P = .02). There
      were no time-dependent changes for either outcome. CONCLUSION: Although the
      proportion of older adults meeting criteria for trauma center transport
      substantially increased with geriatric triage criteria, there were no increases
      in trauma center transports. Adoption of statewide geriatric triage guidelines
      did not decrease mortality in more severely injured older adults but was
      associated with slightly lower mortality in individuals with mild injuries (ISS
      <10) and with more individuals discharged to home. Improving outcomes in injured
      older adults will require further attention to implementation and use of
      geriatric-specific criteria.

PMID- 27696351
TI  - Poundbury Camp in Context-a new Perspective on the Lives of Children from urban
      and rural Roman England.
AB  - OBJECTIVES: The current understanding of child morbidity in Roman England is
      dominated by studies of single sites/regions. Much of the data are derived from
      third to fifth century AD Poundbury Camp, Dorchester, Dorset, considered an
      unusual site due to high levels of non-adult morbidity. There is little
      understanding of children in rural areas, and whether Poundbury Camp was
      representative of Romano-British childhood. MATERIALS AND METHODS: The study
      provides the first large scale analysis of child health in urban and rural Roman
      England, adding to the previously published intra-site analysis of non-adult
      paleopathology at Poundbury Camp. Age-at-death and pathology prevalence rates
      were reassessed for 953 non-adults (0-17 years) from five major urban, six minor
      urban, and four rural sites (first to fifth century AD). The data were compared
      to the results from 364 non-adults from Poundbury Camp. RESULTS: Rural sites
      demonstrated higher levels of infant burials, and greater prevalence of cribra
      orbitalia in the 1.1-2.5 year (TPR 64.3%), and 6.6-10.5 year cohorts (TPR 66.7%).
      Endocranial lesions were more frequent in the minor urban sample (TPR 15.9%).
      Three new cases of tuberculosis were identified in urban contexts. Vitamin D
      deficiency was most prevalent at Poundbury Camp (CPR 18.8%), vitamin C deficiency
      was identified more frequently in rural settlements (CPR 5.9%). DISCUSSION: The
      Poundbury Camp data on morbidity and mortality are not representative of patterns
      in Roman England and other major urban sites. Rural children suffered from a
      distinct set of pathologies described as diseases of deprivation, prompting
      reconsideration of how Romano-British land management affected those at the
      bottom of the social hierarchy.

PMID- 27696352
TI  - Investigating the effects of peptoid substitutions in self-assembly of Fmoc
      diphenylalanine derivatives.
AB  - Low molecular weight agents that undergo self-assembly into fibril networks with
      hydrogel properties are promising biomaterials. Most low molecular weight
      hydrogelators are discovered empirically or serendipitously due to imperfect
      understanding of the mechanisms of self-assembly, the packing structure of self
      assembled materials, and how the self-assembly process corresponds to emergent
      hydrogelation. Herein, the mechanisms of self-assembly and hydrogelation of N
      fluorenylmethoxycarbonyl diphenylalanine (Fmoc-PhePhe), a well-studied low
      molecular weight hydrogelator, is probed by systematic comparison with
      derivatives in which Phe residues are replaced by corresponding N-benzyl glycine
      peptoid (Nphe) analogs. Peptoids are peptidomimetics that shift display of side
      chain functionality from the alpha-carbon to the terminal nitrogen. This alters
      the hydrogen bonding capacity, the side chain presentation geometry, amide
      cis/trans isomerization equilibrium, and beta-sheet potential of the peptoid
      relative to the corresponding amino acid in the context of peptidic polymers. It
      was found that amino acid/peptoid hybrids Fmoc-Phe-Nphe and Fmoc-Nphe-Phe have
      altered fibril self-assembly propensity and reduced hydrogelation capacity
      relative to the parent dipeptide, and that fibril self-assembly of the dipeptoid,
      Fmoc-Nphe-Nphe, is completely curtailed. These findings provide insight into the
      potential of low molecular weight peptoids and peptide/peptoid hybrids as
      hydrogelation agents and illuminate the importance of hydrogen bonding and pi-pi
      interaction geometry in facilitating self-assembly of Fmoc-Phe-Phe.

PMID- 27696353
TI  - Online optimal experimental re-design in robotic parallel fed-batch cultivation
      facilities.
AB  - We present an integrated framework for the online optimal experimental re-design
      applied to parallel nonlinear dynamic processes that aims to precisely estimate
      the parameter set of macro kinetic growth models with minimal experimental
      effort. This provides a systematic solution for rapid validation of a specific
      model to new strains, mutants, or products. In biosciences, this is especially
      important as model identification is a long and laborious process which is
      continuing to limit the use of mathematical modeling in this field. The strength
      of this approach is demonstrated by fitting a macro-kinetic differential equation
      model for Escherichia coli fed-batch processes after 6 h of cultivation. The
      system includes two fully-automated liquid handling robots; one containing eight
      mini-bioreactors and another used for automated at-line analyses, which allows
      for the immediate use of the available data in the modeling environment. As a
      result, the experiment can be continually re-designed while the cultivations are
      running using the information generated by periodical parameter estimations. The
      advantages of an online re-computation of the optimal experiment are proven by a
      50-fold lower average coefficient of variation on the parameter estimates
      compared to the sequential method (4.83% instead of 235.86%). The success
      obtained in such a complex system is a further step towards a more efficient
      computer aided bioprocess development. Biotechnol. Bioeng. 2017;114: 610-619. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27696354
TI  - Life-Space Mobility and Mortality in Older Women: Prospective Results from the
      Study of Osteoporotic Fractures.
AB  - OBJECTIVES: To evaluate the relationship between life-space mobility (extent,
      frequency, independence of movement) and mortality in older women. DESIGN:
      Prospective cohort study. SETTING: Four U.S. clinical sites. PARTICIPANTS: Women
      (N = 1,498) aged 75 to 102 (mean 87.6) followed from 2006 to 2015. MEASUREMENTS:
      Life-space during the past 4 weeks was assessed in an interview, scored from 0
      (daily restriction to bedroom) to 120 (daily trips outside town without
      assistance), and categorized (0-20, 21-40, 41-60, 61-80, 81-120). All-cause
      mortality was the primary outcome; noncancer, cardiovascular, cancer, and
      noncardiovascular noncancer mortality were secondary outcomes. RESULTS: Over a
      mean 5.2 years, 842 (56.2%) women died. Unadjusted risk of all-cause mortality
      was 82.6% in women with the lowest level of life-space (0-20 points) and 36.2% in
      those with the highest level (81-120 points). In multivariable proportional
      hazards models, there was a strong relationship between less life-space and
      greater risk of all-cause mortality (Ptrend < .001). Women with the lowest level
      of life-space (0-20 points) had a risk of all-cause mortality that was 2.4 times
      as high (95% confidence interval (CI) = 1.5-4.0) as that of women with the
      highest level (81-120 points); women with life-space scores between 21 and 60 had
      a risk of all-cause mortality that was 1.5 times as high as that of women with
      the highest level. Each standard deviation decrease in life-space was associated
      with a 1.2 times greater (95% CI = 1.1-1.4) risk of all-cause mortality. Women
      unable to travel beyond their neighborhood without assistance had a risk of all
      cause mortality that was 1.4 times (95% CI = 1.1-1.7) as high as that of women
      who could travel beyond their neighborhood without assistance. Results were
      similar for noncancer, cardiovascular, and other mortality and did not change
      after controlling for underlying disease or living arrangement. CONCLUSION: Life
      space scores of 60 or less were associated with mortality in older women
      independent of other strong risk factors.

PMID- 27696355
TI  - Surgery for women with apical vaginal prolapse.
AB  - BACKGROUND: Apical vaginal prolapse is a descent of the uterus or vaginal vault
      (post-hysterectomy). Various surgical treatments are available and there are no
      guidelines to recommend which is the best. OBJECTIVES: To evaluate the safety and
      efficacy of any surgical intervention compared to another intervention for the
      management of apical vaginal prolapse. SEARCH METHODS: We searched the Cochrane
      Incontinence Group's Specialised Register of controlled trials, which contains
      trials identified from the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, ClinicalTrials.gov, WHO ICTRP and handsearching of journals
      and conference proceedings (searched July 2015) and ClinicalTrials.gov (searched
      January 2016). SELECTION CRITERIA: We included randomised controlled trials
      (RCTs). DATA COLLECTION AND ANALYSIS: We used Cochrane methods. Our primary
      outcomes were awareness of prolapse, repeat surgery and recurrent prolapse (any
      site). MAIN RESULTS: We included 30 RCTs (3414 women) comparing surgical
      procedures for apical vaginal prolapse. Evidence quality ranged from low to
      moderate. Limitations included imprecision, poor methodological reporting and
      inconsistency. Vaginal procedures versus sacral colpopexy (six RCTs, n = 583; one
      to four-year review). Awareness of prolapse was more common after vaginal
      procedures (risk ratio (RR) 2.11, 95% confidence interval (CI) 1.06 to 4.21, 3
      RCTs, n = 277, I2 = 0%, moderate-quality evidence). If 7% of women are aware of
      prolapse after sacral colpopexy, 14% (7% to 27%) are likely to be aware after
      vaginal procedures. Repeat surgery for prolapse was more common after vaginal
      procedures (RR 2.28, 95% CI 1.20 to 4.32; 4 RCTs, n = 383, I2 = 0%, moderate
      quality evidence). The confidence interval suggests that if 4% of women require
      repeat prolapse surgery after sacral colpopexy, between 5% and 18% would require
      it after vaginal procedures.We found no conclusive evidence that vaginal
      procedures increaserepeat surgery for stress urinary incontinence (SUI) (RR 1.87,
      95% CI 0.72 to 4.86; 4 RCTs, n = 395; I2 = 0%, moderate-quality evidence). If 3%
      of women require repeat surgery for SUI after sacral colpopexy, between 2% and
      16% are likely to do so after vaginal procedures. Recurrent prolapse is probably
      more common after vaginal procedures (RR 1.89, 95% CI 1.33 to 2.70; 4 RCTs, n =
      390; I2 = 41%, moderate-quality evidence). If 23% of women have recurrent
      prolapse after sacral colpopexy, about 41% (31% to 63%) are likely to do so after
      vaginal procedures.The effect of vaginal procedures on bladder injury was
      uncertain (RR 0.57, 95% CI 0.14 to 2.36; 5 RCTs, n = 511; I2 = 0%, moderate
      quality evidence). SUI was more common after vaginal procedures (RR 1.86, 95% CI
      1.17 to 2.94; 3 RCTs, n = 263; I2 = 0%, moderate-quality evidence). Dyspareunia
      was also more common after vaginal procedures (RR 2.53, 95% CI 1.17 to 5.50; 3
      RCTs, n = 106, I2 = 43%, low-quality evidence). Vaginal surgery with mesh versus
      without mesh (6 RCTs, n = 598, 1-3 year review). Awareness of prolapse - There
      may be little or no difference between the groups for this outcome (RR 1.08 95%
      CI 0.35 to 3.30 1 RCT n = 54, low quality evidence). The confidence interval was
      wide suggesting that if 18% of women are aware of prolapse after surgery without
      mesh, between 6% and 59% will be aware of prolapse after surgery with mesh.
      Repeat surgery for prolapse - There may be little or no difference between the
      groups for this outcome (RR 0.69, 95% CI 0.30 to 1.60; 5 RCTs, n = 497; I2 = 9%,
      low-quality evidence). If 4% of women require repeat surgery for prolapse after
      surgery without mesh, 1% to 7% are likely to do so after surgery with mesh.We
      found no conclusive evidence that surgery with mesh increases repeat surgery for
      SUI (RR 4.91, 95% CI 0.86 to 27.94; 2 RCTs, n = 220; I2 = 0%, low-quality
      evidence). The confidence interval was wide suggesting that if 2% of women
      require repeat surgery for SUI after vaginal colpopexy without mesh, 2% to 53%
      are likely to do so after surgery with mesh.We found no clear evidence that
      surgery with mesh decreases recurrent prolapse (RR 0.36, 95% CI 0.09 to 1.40; 3
      RCTs n = 269; I2 = 91%, low-quality evidence). The confidence interval was very
      wide and there was serious inconsistency between the studies. Other outcomes
      There is probably little or no difference between the groups in rates of SUI (de
      novo) (RR 1.37, 95% CI 0.94 to 1.99; 4 RCTs, n = 295; I2 = 0%, moderate-quality
      evidence) or dyspareunia (RR 1.21, 95% CI 0.55 to 2.66; 5 RCTs, n = 501; I2 = 0%
      moderate-quality evidence). We are uncertain whether there is any difference for
      bladder injury (RR 3.00, 95% CI 0.91 to 9.89; 4 RCTs, n = 445; I2 = 0%; very low
      quality evidence). Vaginal hysterectomy versus alternatives for uterine prolapse
      (six studies, n = 667)No clear conclusions could be reached from the available
      evidence, though one RCT found that awareness of prolapse was less likely after
      hysterectomy than after abdominal sacrohysteropexy (RR 0.38, 955 CI 0.15 to 0.98,
      n = 84, moderate-quality evidence).Other comparisonsThere was no evidence of a
      difference for any of our primary review outcomes between different types of
      vaginal native tissue repair (two RCTs), comparisons of graft materials for
      vaginal support (two RCTs), different routes for sacral colpopexy (four RCTs), or
      between sacral colpopexy with and without continence surgery (four RCTs).
      AUTHORS' CONCLUSIONS: Sacral colpopexy is associated with lower risk of awareness
      of prolapse, recurrent prolapse on examination, repeat surgery for prolapse,
      postoperative SUI and dyspareunia than a variety of vaginal interventions.The
      limited evidence does not support use of transvaginal mesh compared to native
      tissue repair for apical vaginal prolapse. Most of the evaluated transvaginal
      meshes are no longer available and new lighter meshes currently lack evidence of
      safetyThe evidence was inconclusive when comparing access routes for sacral
      colpopexy.No clear conclusion can be reached from the available data comparing
      uterine preserving surgery versus vaginal hysterectomy for uterine prolapse.

PMID- 27696356
TI  - Investigation of an "alternate water supply system" in enzymatic hydrolysis in
      the processive endocellulase Cel7A from Rasamsonia emersonii by molecular
      dynamics simulation.
AB  - Cel7A from Rasamsonia emersonii is one of the processive endocellulases
      classified under family 7 glycoside hydrolase. Molecular dynamics simulations
      were carried out to obtain the optimized sliding and hydrolyzing conformations,
      in which the reducing ends of sugar chains are located on different sites.
      Hydrogen bonds are investigated to clarify the interactions between protein and
      substrate in either conformation. Nine hydrogen bonding interactions are
      identified in the sliding conformation, and six similar interactions are also
      found correspondingly in the hydrolyzing conformation. In addition, four strong
      hydrophobic interactions are also determined. The domain cross-correlation map
      analysis shows movement correlation of protein including autocorrelation between
      residues. The root mean square fluctuations analysis represents the various
      flexibilities of different fragment in the two conformations. Comparing the two
      conformations reveals the water-supply mechanism of selective hydrolysis of
      cellulose in Cel7A. The mechanism can be described as follow. When the reducing
      end of substrate slides from the unhydrolyzing site (sliding conformation) to the
      hydrolyzing site (hydrolyzing conformation), His225 is pushed down and rotated,
      the rotation leads to the movement of Glu209 with the interstrand hydrogen
      bonding in beta-sheet. It further makes Asp211 close to the hydrolysis center and
      provides a water molecule bounding on its carboxyl in the previous unhydrolyzing
      site. After the hydrolysis takes place and the product is excluded from the
      enzyme, the Asp211 comes back to its initial position. In summary, Asp211 acts as
      an elevator to transport outer water molecules into the hydrolysis site for every
      other glycosidic bond.

PMID- 27696357
TI  - Disturbances and noise: Defining furrow-form enamel hypoplasia.
AB  - OBJECTIVES: The investigation of the record of growth locked in dental enamel
      provides a unique opportunity to build a comprehensive picture of growth
      disruption episodes during childhood. This study presents a new methodological
      basis for the analysis of enamel growth disruptions (enamel hypoplasia) using
      incremental microstructures of enamel. METHODS: A three-dimensional technique
      based upon use of an Alicona 3D Infinite Focus imaging microscope and software is
      used to record developmental features in the enamel of human permanent mandibular
      lateral incisors of one individual from the Neolithic site of Catalhoyuk
      (Turkey). Using this new technique, perikymata are measured down the longitudinal
      axis of the crown from the incisal margin to the cervix and perikyma spacing
      profiles are constructed with this new technique. A mathematical basis for the
      detection of spacing anomalies, which serve as indicators of enamel hypoplasia is
      presented based upon these profiles. RESULTS: Three clearly delineated defects
      were identified visually, then matched and confirmed metrically using the enamel
      surface and perikyma spacing profiles. DISCUSSION: Human growth has often been
      used as an indicator of health in past societies because of developmental
      sensitivity to fluctuations in nutritional status and disease load. Hence,
      standardization of furrow-form defect identification is of crucial importance for
      reducing the amount of current subjectivity in the determination of a threshold
      for the identification of defects among individuals of past populations. The
      method presented here, which is based on microscopic images of the tooth crown as
      well as recorded measurements of incremental structures, represents a combined
      visual-metric approach using LOWESS residuals, and as such provides a substantial
      advancement to previous methods. It is therefore recommended that additional
      studies be carried out with this methodology to determine whether this method
      improves the reliability of enamel defect identification among individuals
      recovered from bioarchaeological contexts.

PMID- 27696358
TI  - The Movement Tracker: A Flexible System for Automated Movement Analysis in
      Invertebrate Model Organisms.
AB  - Phenotyping strategies in simple model organisms such as D. melanogaster and C.
      elegans are often broadly limited to growth, aging, and fitness. Recently, a
      number of physical setups and video tracking software suites have been developed
      to allow for accurate, quantitative, and high-throughput analysis of movement in
      flies and worms. However, many of these systems require precise experimental
      setups and/or fixed recording formats. We report here an update to the Parallel
      Worm Tracker software, which we termed the Movement Tracker. The Movement Tracker
      allows variable experimental setups to provide cross-platform automated
      processing of a variety of movement characteristics in both worms and flies and
      permits the use of simple physical setups that can be readily implemented in any
      laboratory. This software allows high-throughput processing capabilities and high
      levels of flexibility in video analysis, providing quantitative movement data on
      C. elegans and D. melanogaster in a variety of different conditions. (c) 2016 by
      John Wiley & Sons, Inc.

PMID- 27696359
TI  - Pica in Rats as a Preclinical Model of Emesis.
AB  - The ability to assess the potential for gastrointestinal adverse events in a
      preclinical setting is a challenge in the development of new drugs, as the vast
      majority of in vivo research is conducted in rodent species lacking a vomiting
      reflex. The use of higher species capable of emesis is often limited by cost,
      technical experience, and relevant efficacy models to define a therapeutic index.
      Additionally, investigators should be mindful of ethical considerations when
      using more sentient species when an alternative in lower species is available.
      This unit describes the use of pica behavior in rodents as an alternative for
      evaluating emetic potential in vivo. After an acclimation period, the incidence
      of rats engaging in pica following the administration of a test article can be
      used to generate a dose-response curve of the pica behavior. When linked with an
      appropriate efficacy model, this allows compounds to be ranked based on
      therapeutic index. (c) 2016 by John Wiley & Sons, Inc.

PMID- 27696360
TI  - Automatic Dendritic Spine Quantification from Confocal Data with Neurolucida 360.
AB  - Determining the density and morphology of dendritic spines is of high biological
      significance given the role of spines in synaptic plasticity and in
      neurodegenerative and neuropsychiatric disorders. Precise quantification of
      spines in three dimensions (3D) is essential for understanding the structural
      determinants of normal and pathological neuronal function. However, this
      quantification has been restricted to time- and labor-intensive methods such as
      electron microscopy and manual counting, which have limited throughput and are
      impractical for studies of large samples. While there have been some automated
      software packages that quantify spine number, they are limited in terms of their
      characterization of spine structure. This unit presents methods for objective
      dendritic spine morphometric analysis by providing image acquisition parameters
      needed to ensure optimal data series for proper spine detection,
      characterization, and quantification with Neurolucida 360. These protocols will
      be a valuable reference for scientists working towards quantifying and
      characterizing spines. (c) 2016 by John Wiley & Sons, Inc.

PMID- 27696361
TI  - The Neonatal Ventral Hippocampal Lesion (NVHL) Rodent Model of Schizophrenia.
AB  - Animal models are crucial to the study of the neurobiological bases of
      psychiatric disorders, but schizophrenia is a particularly challenging disorder
      to model given the complexity and heavily verbal nature of its symptoms. This
      unit describes a developmental surgical rodent model of schizophrenia, the
      neonatal ventral hippocampal lesion (NVHL) model. This widely used model produces
      reliable behavioral abnormalities that are comparable to those observed in
      patients, as well as anatomical and neurophysiological disruptions in forebrain
      areas that are also implicated in schizophrenia. A brief background of the
      development and validity of the NVHL model is discussed here, along with detailed
      procedures for producing the model in rats. Critical issues particular to
      neonatal surgery are discussed, and representative histological and behavioral
      results are presented. (c) 2016 by John Wiley & Sons, Inc.

PMID- 27696362
TI  - Cigarette Smoke Extract: A Preclinical Model of Tobacco Dependence.
AB  - Animal models are used to study many human diseases, one of which is tobacco
      addiction. Most preclinical models use nicotine alone, although there are >7000
      constituents present in tobacco smoke. The clinical literature suggests that
      cigarettes have a strong addictive potential, which is not paralleled in
      preclinical studies using nicotine alone. In order to address the gap between
      clinical and preclinical literature on tobacco dependence, cigarette smoke
      extracts containing tobacco constituents have been developed. This unit describes
      a procedure for producing an aqueous cigarette smoke extract (CSE) which animals
      readily self-administer. In addition, we describe how to make the apparatus for
      producing CSE and how to analyze the solution for nicotine content. (c) 2016 by
      John Wiley & Sons, Inc.

PMID- 27696363
TI  - Cerebral Cortex Electroporation to Study Projection Neuron Migration.
AB  - Brain electroporation is a rapid and powerful approach to study neuronal
      development. In particular, this technique has become a method of choice for
      studying the process of radial migration of projection neurons in the embryonic
      cerebral cortex. This method has considerably helped to describe in detail the
      different steps of radial migration and to characterize the molecular mechanisms
      controlling this process. Delineating the complexities of neuronal migration is
      critical to our understanding not only of normal cerebral cortex formation but
      also of neurodevelopmental disorders resulting from neuronal migration defects.
      Here, we describe in detail the protocols to perform in utero or ex vivo
      electroporation of progenitor cells in the ventricular zone of the cerebral
      cortex with the aim of studying the process of radial migration of projection
      neurons during embryonic development. (c) 2016 by John Wiley & Sons, Inc.

PMID- 27696364
TI  - Skeletal assessment and secular changes in knee development: a radiographic
      approach.
AB  - OBJECTIVES: The purpose of this study is to conduct an analysis of ossification
      patterns in the distal femoral, proximal tibial, and proximal fibular epiphyses,
      and the patella. The results generated from this analysis will be compared with
      previous standards published by Elgenmark () and Garn et al. () to determine if
      clinical and skeletal age assessment standards should be updated for contemporary
      Americans. MATERIALS AND METHODS: Using the Pediatric Radiology Interactive Atlas
      (Patricia), a total of 1,317 epiphyses were scored for presence or absence from
      radiographs of 1,056 white individuals born in or after 1990. Statistical
      modeling of epiphyseal appearance was conducted for all major percentiles,
      including the 5th and 95th percentiles through logistic regression. RESULTS:
      Compared with Elgenmark () and Garn et al. (), our data suggest that the distal
      femoral and proximal tibial epiphyses show overall earlier ossification, while
      the proximal fibular epiphysis shows later ossification. When examining the
      pooled sex 50th percentile for our data, we found that ossification timing
      differences are 1.2 weeks earlier in the distal femoral epiphysis, 2.1 weeks
      earlier in the proximal tibial epiphysis, and 1.4 years later in the proximal
      fibular epiphysis. DISCUSSION: The epiphyses that appear early in life, for
      example the distal femoral epiphysis, require gestational age information to
      accurately estimate appearance times. There are considerable differences between
      the ossification timing patterns presented in this study and those of previous
      standards, which did not include gestational ages. Several factors may explain
      the observed differences in the epiphyses of the knee including: the availability
      of gestational age information, the analysis of longitudinal versus cross
      sectional data, differences in socioeconomic status and prenatal care, and
      secular change. KEYWORDS age estimation, growth standards, ossification, skeletal
      maturation, subadult/juvenile growth.

PMID- 27696365
TI  - ICP assessment by ultrasonic time of flight: the first publication.

PMID- 27696366
TI  - Five-year study of quality of life in myotonic dystrophy.
AB  - Background - Myotonic dystrophy type 1 (DM1) is the most common muscular
      dystrophy in adults. There is a complete lack of studies that assessed quality of
      life (QoL) trajectory during time in DM1 cohorts. Aim - To analyze changes of QoL
      in patients with DM1 during a 5-year follow-up period and to assess
      responsiveness of the SF-36 questionnaire. Patients and Method - At the baseline,
      this study comprised 84 DM1 patients, of whom 62 were retested after the mean
      period of 64.2 +/- 3.9 months. Severity of muscular weakness was assessed using
      the Muscular Impairment Rating Scale (MIRS). Patients completed Serbian version
      of the SF-36 questionnaire as a measure of health-related QoL. Results - After 5
      years, MIRS score of our DM1 patients showed significant progression of 0.5 grade
      (P < 0.01). All mental subdomains, role physical, and total SF-36 scores
      significantly improved after 5 years (P < 0.01). Unexpectedly, worsening of
      muscular weakness from mild to severe was in association with improvement of QoL.
      Conclusion - QoL improved in our cohort of DM1 patients during a 5-year period
      despite the progression of the disease. SF-36 should be used with caution as a
      patient-reported outcome measure in DM1 clinical trials.

PMID- 27696367
TI  - Association of hepatitis B virus infection with decreased ischemic stroke.
AB  - OBJECTIVES: Inflammatory processes (both infections and autoimmune diseases) may
      cause endothelial dysfunction and arterial atherosclerosis, subsequently
      increasing the risk of acute ischemic stroke (AIS). In this investigation, we
      analyzed the association between hepatitis B virus (HBV) infection and AIS risk.
      METHODS: A Taiwan national insurance claims data set of 1,000,000 patients was
      used to extract 22,303 patients with HBV and 89,212 randomly selected sex- and
      age-matched controls from the beginning of 2000 to the end of 2006. Both groups
      were followed up until the appearance of AIS or the end of 2011. AIS risk was
      measured using the Cox proportional regression model. RESULTS: After adjusting
      for the relevant covariates, the HBV group exhibited a lower AIS risk (adjusted
      hazard ratio [aHR] = 0.77, 95% confidence interval [CI]: 0.66-0.89) compared with
      the controls at the end of follow-up. Under the condition of no comorbidities,
      patients with HBV had a lower AIS risk compared with the controls (aHR = 0.65,
      95% CI: 0.48-0.87). In 3 age-stratified subgroups, HBV was correlated with a
      significantly diminished risk of AIS (age <= 49 years: aHR = 0.57, 95% CI: 0.39
      0.82; age 50-64 years: aHR = 0.65, 95% CI: 0.53-0.80; age >= 65 years: aHR =
      0.96, 95% CI: 0.76-1.23). CONCLUSION: HBV was correlated with a reduced risk of
      AIS development. Although a decrease in AIS risk was noted in the patients with
      HBV, preventing the development of AIS in this population warrants further
      attention.

PMID- 27696368
TI  - Subthalamic oscillatory activity in parkinsonian patients with off-period
      dystonia.
AB  - OBJECTIVES: The study was aimed to explore oscillatory activity in the
      subthalamic nucleus (STN) in Parkinson's disease (PD) with off-period dystonia, a
      type of levodopa-induced dyskinesias (LID). METHODS: Eighteen patients with PD
      who underwent STN DBS were studied. Nine patients had dyskinesia defined as the
      LID group and nine patients who did not present any sign of dyskinesia were
      defined as the control group. Microelectrode recordings in the STN together with
      electromyogram (EMG) were recorded. Spectral and coherence analyses were
      performed to study the neuronal oscillations in relation to limb muscles.
      RESULTS: Two hundred and fifteen neurons were identified. There were 39 neurons
      with tremor-frequency band (4-7 Hz) oscillation, 57 neurons with beta-frequency
      band (12-30 Hz, beta-FB) oscillation and 100 neurons without oscillation, and 19
      neurons with very low-frequency band oscillation at a mean peak power of 1.2 +/-
      0.5 Hz (LFB). These LFB oscillatory neurons (n = 15) were frequently
      significantly coherent with EMG of off-period dystonia. Notably, 89% (n = 17)
      neurons with LFB oscillation were found in the patients in the off-dystonia
      group. The age at onset of PD, duration of PD, and levodopa equivalent dose daily
      consumption were statistically different between two groups (P < 0.05).
      CONCLUSIONS: Subthalamic LFB oscillatory neurons seem to play an important role
      in the genesis of off-period dystonia in advanced PD. Clinical and demographic
      analyses confirmed that the earlier age at onset of PD, longer duration of PD,
      and levodopa exposure are important risk factors in the development of the type
      of LID.

PMID- 27696369
TI  - Non-invasive ICP assessment through time of flight.

PMID- 27696370
TI  - Nano-mechanical characterization of disassembling amyloid fibrils using the Peak
      Force QNM method.
AB  - The comprehensive understanding of disassembly mechanism of amyloid fibrils
      requires nano-scale characterization of the mechanical properties of amyloid
      fibrils during the disassembly process. In this work, gemini surfactant C12 C6
      C12 Br2 micelles were used as a probe to disassemble Abeta(1-40) fibrils. The
      microstructure evolution and nano-mechanical properties of Abeta(1-40) fibrils
      during the disassembly process were systematically investigated by the Peak Force
      Quantitative Nano-mechanical (PF-QNM) technique. The results show an obvious
      decrease in Young's modulus of mature fibrils with high beta-sheet contents (2.4
      +/- 1.0 GPa) in comparison to the resulting peptide/surfactant complexes (1.1 +/-
      0.8 GPa) with loose surface structures. Interestingly, the Young's modulus of
      spherical peptide/surfactant complexes on the core was more than 3 GPa. This
      strategy can be used as a standard protocol to investigate the interaction
      mechanism between amyloid fibrils and small molecules, which may open up new
      possibilities to explore the mechanism of relevant human diseases.

PMID- 27696371
TI  - Comprehensive reconstruction and in silico analysis of Aspergillus niger genome
      scale metabolic network model that accounts for 1210 ORFs.
AB  - Aspergillus niger is one of the most important cell factories for industrial
      enzymes and organic acids production. A comprehensive genome-scale metabolic
      network model (GSMM) with high quality is crucial for efficient strain
      improvement and process optimization. The lack of accurate reaction equations and
      gene-protein-reaction associations (GPRs) in the current best model of A. niger
      named GSMM iMA871, however, limits its application scope. To overcome these
      limitations, we updated the A. niger GSMM by combining the latest genome
      annotation and literature mining technology. Compared with iMA871, the number of
      reactions in iHL1210 was increased from 1,380 to 1,764, and the number of unique
      ORFs from 871 to 1,210. With the aid of our transcriptomics analysis, the
      existence of 63% ORFs and 68% reactions in iHL1210 can be verified when glucose
      was used as the only carbon source. Physiological data from chemostat
      cultivations, 13 C-labeled and molecular experiments from the published
      literature were further used to check the performance of iHL1210. The average
      correlation coefficients between the predicted fluxes and estimated fluxes from
      13 C-labeling data were sufficiently high (above 0.89) and the prediction of cell
      growth on most of the reported carbon and nitrogen sources was consistent. Using
      the updated genome-scale model, we evaluated gene essentiality on synthetic and
      yeast extract medium, as well as the effects of NADPH supply on glucoamylase
      production in A. niger. In summary, the new A. niger GSMM iHL1210 contains
      significant improvements with respect to the metabolic coverage and prediction
      performance, which paves the way for systematic metabolic engineering of A.
      niger. Biotechnol. Bioeng. 2017;114: 685-695. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696372
TI  - Antibiotic treatment for the sexual partners of women with bacterial vaginosis.
AB  - BACKGROUND: Bacterial vaginosis (BV) is an infection that has a prevalence
      between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal
      flora. Microorganisms associated with BV have been isolated from the normal flora
      of the male genital tract, and their presence could be related to the recurrence
      of BV after antibiotic treatment. Therefore, the treatment of sexual partners
      could decrease the recurrence of infection and possibly the burden of the
      disease. OBJECTIVES: To assess the effectiveness in women and the safety in men
      of concurrent antibiotic treatment for the sexual partners of women treated for
      BV. SEARCH METHODS: We searched the Cochrane Sexually Transmitted Infections
      Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016),
      MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23
      July 2016), the World Health Organization (WHO) International Clinical Trials
      Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and
      the Web of ScienceTM (2001 to 23 July 2016). We also handsearched conference
      proceedings, contacted trial authors and reviewed the reference lists of
      retrieved studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) that
      compared the concurrent use of any antibiotic treatment with placebo, no
      intervention or any other intervention by the sexual partners of women treated
      for BV. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed
      trials for inclusion, extracted data and assessed the risk of bias in the
      included studies. We resolved any disagreements through consensus. We assessed
      the quality of the evidence using the GRADE approach. MAIN RESULTS: Seven RCTs
      (1026 participants) met our inclusion criteria, and pharmaceutical industry
      funded four of these trials. Five trials (854 patients) compared any antibiotic
      treatment of sexual partners with placebo. Based on high quality evidence,
      antibiotic treatment does not increase the rate of clinical or symptomatic
      improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence
      interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00
      to 1.12; 577 patients, three studies, respectively), between the first and fourth
      week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95%
      CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth
      week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95%
      CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic
      treatment does not led to a lower recurrence during the first and fourth week (RR
      1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or
      after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372
      participants, three studies; low quality evidence) in women, but increases the
      frequency of adverse events (most frequently gastrointestinal symptoms) reported
      by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three
      studies; low quality evidence). Two trials (172 participants) compared any
      antibiotic treatment for sexual partners with no intervention. When we compared
      it with no intervention, the effects of antibiotic treatment on recurrence rate
      after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study),
      clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to
      1.25; 152 participants, two studies) and symptomatic improvement after the fourth
      week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise
      and there were no differences between groups. We downgraded the quality of the
      evidence to low or very low. AUTHORS' CONCLUSIONS: High quality evidence shows
      that antibiotic treatment for sexual partners of women with BV, compared with
      placebo, does not increase the rate of clinical or symptomatic improvement during
      the first, between the first and fourth or after the fourth week into the women.
      Low quality evidence suggests that antibiotic treatment does not led to a lower
      recurrence rate during the first and fourth or after the fourth week of treatment
      into the women, but increases the frequency of adverse events reported by sexual
      partners. Finally, compared with no intervention, antibiotic treatment does not
      decrease the recurrence rate after the fourth week and does not increase the
      frequency of clinical or symptomatic improvement between the first and fourth or
      after the fourth week into the women, respectively.

PMID- 27696373
TI  - Delirium After Spine Surgery in Older Adults: Incidence, Risk Factors, and
      Outcomes.
AB  - OBJECTIVES: To characterize the incidence, risk factors, and consequences of
      delirium in older adults undergoing spine surgery. DESIGN: Prospective
      observational study. SETTING: Academic medical center. PARTICIPANTS: Individuals
      aged 70 and older undergoing spine surgery (N = 89). MEASUREMENTS: Postoperative
      delirium and delirium severity were assessed using validated methods, including
      the Confusion Assessment Method (CAM), CAM for the Intensive Care Unit, Delirium
      Rating Scale-Revised-98, and chart review. Hospital-based outcomes were obtained
      from the medical record and hospital charges from data reported to the state.
      RESULTS: Thirty-six participants (40.5%) developed delirium after spine surgery,
      with 17 (47.2%) having purely hypoactive features. Independent predictors of
      delirium were lower baseline cognition, higher average baseline pain, more
      intravenous fluid administered, and baseline antidepressant medication. In
      adjusted models, the development of delirium was independently associated with
      higher quintile of length of stay (odds ratio (OR) = 3.66, 95% confidence
      interval (CI) = 1.48-9.04, P = .005), higher quintile of hospital charges (OR =
      3.49, 95% CI = 1.35-9.00, P = .01), and lower odds of discharge to home (OR =
      0.22, 95% CI = 0.07-0.69, P = .009). Severity of delirium was associated with
      higher quintile of hospital charges and lower odds of discharge to home.
      CONCLUSION: Delirium is common after spine surgery in older adults, and baseline
      pain is an independent risk factor. Delirium is associated with longer stay,
      higher charges, and lower odds of discharge to home. Thus, prevention of delirium
      after spine surgery may be an important quality improvement goal.

PMID- 27696374
TI  - Letter to the editor: Reply to Kasvosve (2016).

PMID- 27696375
TI  - Establishing and prioritizing research questions for the treatment of alopecia
      areata: the Alopecia Areata Priority Setting Partnership.
AB  - BACKGROUND: Alopecia areata (AA) is a common hair loss disorder that results in
      patchy to complete hair loss. Many uncertainties exist around the most effective
      treatments for this condition. OBJECTIVES: To identify uncertainties in AA
      management and treatment that are important to both service users (people with
      hair loss, carers and relatives) and healthcare professionals. METHODS: An AA
      priority setting partnership was established between patients, their carers and
      relatives, and healthcare professionals to identify the most important
      uncertainties in AA. The methodology of the James Lind Alliance was followed to
      ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747
      treatment uncertainties were submitted by 912 participants, of which 1012
      uncertainties relating to AA (and variants) were analysed. Questions were
      combined into 'indicative uncertainties' following a structured format. A series
      of ranking exercises further reduced this list to a top 25 that were taken to a
      final prioritization workshop where the top 10 priorities were agreed.
      CONCLUSIONS: We present the top 10 research priorities for AA to guide
      researchers and funding bodies to support studies important to both patients and
      clinicians.

PMID- 27696376
TI  - Evaluation of outcome after cardiomyotomy for achalasia using the Chicago
      classification.
AB  - BACKGROUND: Achalasia can be subdivided into manometric subtypes according to the
      Chicago classification. These subtypes are proposed to predict outcome after
      treatment. This hypothesis was tested using a database of patients who underwent
      laparoscopic Heller's cardiomyotomy with anterior fundoplication. METHODS: All
      patients who underwent Heller's cardiomyotomy for achalasia between June 1993 and
      March 2015 were identified from an institutional database. Manometry tracings
      were retrieved and re-reported according the Chicago classification. Outcome was
      assessed by a postal questionnaire, and designated a success if the modified
      Eckardt score was 3 or less, and the patient had not undergone subsequent surgery
      or pneumatic dilatation. Difference in outcome after cardiomyotomy was analysed
      with a mixed-effects logistic regression model. RESULTS: Sixty, 111 and 24
      patients had type I, II and II achalasia respectively. Patients with type III
      achalasia were more likely to be older than those with type I or II (mean age 63
      versus 50 and 49 years respectively; P = 0.001). Some 176 of 195 patients
      returned questionnaires after surgery. Type III achalasia was less likely to have
      a successful outcome than type II (odds ratio (OR) 0.38, 95 per cent c.i. 0.15 to
      0.94; P = 0.035). There was no significant difference in outcome between types I
      and II achalasia (II versus I: OR 0.87, 0.47 to 1.60; P 0.663). The success rate
      at 3-year follow-up was 69 per cent (22 of 32) for type I, 66 per cent (33 of 50)
      for type II and 31 per cent (4 of 13) for type III. CONCLUSION: Type III
      achalasia is a predictor of poor outcome after cardiomyotomy. There was no
      difference in outcome between types I and II achalasia.

PMID- 27696377
TI  - Responsiveness of 8 Patient-Reported Outcomes Measurement Information System
      (PROMIS) measures in a large, community-based cancer study cohort.
AB  - BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS)
      was a National Institutes of Health-funded initiative to develop measures of
      symptoms and function. Responsiveness is the degree to which a measure can detect
      underlying changes over time. The objective of the current study was to document
      the responsiveness of 8 PROMIS measures in a large, population-based cancer
      cohort. METHODS: The Measuring Your Health study recruited 2968 patients who were
      diagnosed with 1 of 7 cancers between 2010 and 2012 through 4 Surveillance,
      Epidemiology, and End Results registries. Participants completed a baseline
      survey (6-13 months after diagnosis) and a 6-month follow-up survey. Changes in 8
      PROMIS scores were compared with global ratings of transition, changes in
      performance status, and clinical events. RESULTS: Measures were responsive to 6
      month declines and improvements in performance status with small to large effect
      sizes (ES) (Cohen d = 0.34-0.71; P < .01). Mean changes and effect sizes were
      larger for participants who reported declines compared with those who reported
      improvements. Small-to-medium ES were observed in patients who reported being "a
      little" worse (d = 0.31-0.56), and medium-to-large ES were observed in those who
      reported being "a lot" worse (d = 0.53-0.72). Hospitalized participants reported
      significant score increases, resulting in worsening of pain (d = 0.51), fatigue
      (d = 0.35), and depression (d = 0.57; all P < .01). Cancer recurrence and
      progression were associated with smaller increases in pain, fatigue, and sleep
      disturbance (d = 0.22-0.27). CONCLUSIONS: The current results indicated that all
      8 PROMIS measures were sensitive to patient-perceived worsening and improvement
      and to major clinical events. These findings will be able to inform the design
      and interpretation of future research studies and clinical initiatives
      administering PROMIS measures. Cancer 2017;123:327-335. (c) 2016 American Cancer
      Society.

PMID- 27696379
TI  - Anatomical versus non-anatomical liver resection for hepatocellular carcinoma
      exceeding Milan criteria.
AB  - BACKGROUND: Liver resection is effective for hepatocellular carcinoma (HCC)
      exceeding the Milan criteria in selected patients. However, the benefit of
      anatomical resection (AR) versus non-anatomical resection (NAR) has not been
      clarified in this patient subgroup. This study aimed to compare outcomes between
      AR and NAR for HCC exceeding the Milan criteria. METHODS: Data on consecutive
      patients with HCC exceeding the Milan criteria who underwent liver resection with
      curative intent over a recent 6-year interval were extracted from a prospective
      single-centre HCC database and examined retrospectively. The postoperative
      outcomes of patients were compared before and after propensity score matching.
      RESULTS: Some 546 patients were included: 264 in the AR and 282 in the NAR group.
      In the original cohort, the AR group contained more patients with larger tumours,
      multiple tumours, macroscopic portal vein tumour thrombi, incomplete tumour
      capsules and microscopic vascular invasion. After propensity score matching, 177
      pairs of patients were selected. The baseline data, including liver function and
      tumour burden, were similar in the matched groups. The 3-year recurrence-free
      survival rate was comparable between the matched NAR and AR groups (36.5 versus
      28.5 per cent; P = 0.448). Similar results were observed for 3-year overall
      survival (57.5 versus 50.3 per cent; P = 0.385), recurrence patterns and early
      recurrence rates (57.6 per cent versus 59.9 per cent; P = 0.712). CONCLUSION: AR
      and NAR achieved favourable and similar outcomes for HCC exceeding the Milan
      criteria in selected patients.

PMID- 27696381
TI  - Climate change and the epidemiology of selected tick-borne and mosquito-borne
      diseases: update from the International Society of Dermatology Climate Change
      Task Force.
AB  - Climate change refers to variation in the climate of a specific region or
      globally over time. A change has been reported in the epidemiology of tick- and
      mosquito-borne diseases in recent decades. Investigators have postulated that
      this effect may be associated with climate change. We reviewed the English
      language literature describing changes in the epidemiology of specific tick- and
      mosquito-borne diseases, including the tick-borne diseases of Lyme disease,
      tularemia, Crimean-Congo hemorrhagic fever, Mediterranean spotted fever, and
      Rocky Mountain spotted fever and the mosquito-borne diseases of dengue, malaria,
      West Nile virus infection, Ross River virus disease, and Barmah Forest virus
      disease. We postulate that the changing epidemiology of tick- and mosquito-borne
      diseases is related to climate change.

PMID- 27696380
TI  - Phase 2 study of dasatinib in patients with alveolar soft part sarcoma,
      chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor.
AB  - BACKGROUND: Alveolar soft part sarcoma (ASPS), chondrosarcoma (CS), chordoma,
      epithelioid sarcoma, and solitary fibrous tumor (SFT) are malignant tumors that
      are relatively resistant to chemotherapy and for which more effective drug
      therapy is needed. METHODS: The 5 listed subtypes were enrolled into a single
      indolent sarcoma cohort in a phase 2 study of dasatinib using a Bayesian
      continuous monitoring rule for enrollment. The primary objective was to estimate
      the 6-month progression-free survival (PFS) rate according to the Choi criteria
      with a target of >=50%. Cross-sectional imaging was performed before the start of
      treatment, every 2 months for 6 months, and then every 3 months during treatment.
      The 2- and 5-year survival rates were determined. RESULTS: One hundred sixteen
      patients were enrolled within 45 months, and 109 began treatment with dasatinib.
      The 6-month PFS rate and the median PFS were 48% and 5.8 months, respectively.
      The PFS rate at 6 months was highest with ASPS (62%) and lowest with SFT (30%).
      More than 10% of the patients with ASPS, CS, or chordoma had stable disease for
      more than 1 year. Collectively, for all 5 subtypes, the 2- and 5-year overall
      survival rates were 44% and 13%, respectively. An objective response was observed
      in 18% of the patients with CS or chordoma. CONCLUSIONS: Dasatinib failed to
      achieve control of sarcoma growth for at least 6 months in more than 50% of the
      patients in this trial according to the Choi tumor response criteria. An
      objective tumor response and prolonged stable disease was observed in >10% of
      patients with CS or chordoma. Cancer 2017;90-97. (c) 2016 American Cancer
      Society.

PMID- 27696382
TI  - Prognostic impact of extracapsular lymph node involvement after neoadjuvant
      therapy and oesophagectomy.
AB  - BACKGROUND: The significance of extracapsular lymph node involvement (LNI) is
      unclear in patients with oesophageal cancer who have undergone neoadjuvant
      treatment followed by oesophagectomy. The aim of this study was to assess the
      incidence and prognostic significance of extracapsular LNI in a large multicentre
      series of consecutive patients with oesophageal cancer treated by neoadjuvant
      chemotherapy or chemoradiotherapy and surgery. METHODS: Data from a consecutive
      series of patients treated at two European centres were analysed. All patients
      with squamous cell carcinoma or adenocarcinoma of the oesophagus or gastro
      oesophageal junction, who received neoadjuvant chemotherapy or chemoradiation
      followed by transthoracic oesophagectomy and two-field lymphadenectomy with
      curative intent, were included. RESULTS: Between January 2000 and September 2013,
      704 patients underwent oesophagectomy after neoadjuvant therapy. A median of 28
      (range 5-77) nodes per patient was recovered. Some 347 patients (49.3 per cent)
      had no LNI (ypN0). Of the remaining 357 patients (50.7 per cent) with LNI (ypN1
      3), extracapsular LNI was found in 190 (53.2 per cent). Five-year overall
      survival rates were 62.7 per cent for patients with N0 disease, 44.9 per cent for
      patients without extracapsular spread and 14.0 per cent where extracapsular LNI
      was identified (P < 0.001). Multivariable analyses demonstrated the presence of
      extracapsular LNI as an independent prognostic factor. CONCLUSION: The presence
      of extracapsular LNI after neoadjuvant therapy carries a poor prognosis.

PMID- 27696383
TI  - Rab11 collaborates E-cadherin to promote collective cell migration and indicates
      a poor prognosis in colorectal carcinoma.
AB  - BACKGROUND: Collective cell migration, whereby the cell-cell contacts such as E
      cadherin are maintained during migration, has only recently emerged, and its
      detailed mechanisms are still unclear. In this study, the role of Rab11, which
      functions in recycling endosomes, and its relationship to E-cadherin in
      colorectal carcinoma were identified, and the role of Rab11 in the collective
      cell migration of colon cancer cells was clarified. MATERIALS AND METHODS: A
      total of 107 patients with surgically resected colorectal carcinoma were enrolled
      in this immunohistochemical study. Relationships between the overexpression of
      Rab11 and E-cadherin and survival were evaluated. The cell biology of Rab11
      overexpression or knock-down in HT-29 colon cells was studied. RESULTS: The
      expression of Rab11 and E-cadherin was not correlated with the stage of cancer or
      lymph node metastasis. However, the overall survival was poor in the group of 67
      patients with duo-positive Rab11 and E-cadherin expression compared to the group
      (40 patients) without dual-positive expression (P = 0.038). Rab11 was
      demonstrated to have a physical interaction with E-cadherin, and overexpression
      of Rab11 was found to promote collective cell migration through the increased
      distribution of E-cadherin, which enhanced cell-cell connections. In addition,
      Rac1 activation and matrix metalloproteinase-2 expressions were upregulated upon
      Rab11 expression. CONCLUSIONS: This study demonstrated that Rab11 and E-cadherin
      expressions are indicators of poor survival time in colorectal carcinoma, but
      that Rab11 overexpression may contribute to increased collective cell invasion in
      colorectal carcinoma.

PMID- 27696378
TI  - Probiotics, fibre and herbal medicinal products for functional and inflammatory
      bowel disorders.
AB  - : Functional bowel disorders (FBD), mainly irritable bowel syndrome (IBS) and
      functional constipation (FC, also called chronic idiopathic constipation), are
      very common worldwide. Inflammatory bowel disease (IBD), including ulcerative
      colitis and Crohn's disease, although less common, has a strong impact on
      patients' quality of life, as well as being highly expensive for our healthcare.
      A definite cure for those disorders is still yet to come. Over the years, several
      therapeutic approaches complementary or alternative to traditional
      pharmacological treatments, including probiotics, prebiotics, synbiotics, fibre
      and herbal medicinal products, have been investigated for the management of both
      groups of diseases. However, most available studies are biased by several
      drawbacks, including small samples and poor methodological quality. Probiotics,
      in particular Saccharomyces boulardii and Lactobacilli (among which Lactobacillus
      rhamnosus), synbiotics, psyllium, and some herbal medicinal products, primarily
      peppermint oil, seem to be effective in ameliorating IBS symptoms. Synbiotics and
      fibre seem to be beneficial in FC patients. The probiotic combination VSL#3 may
      be effective in inducing remission in patients with mild-to-moderate ulcerative
      colitis, in whom Escherichia coli Nissle 1917 seems to be as effective as
      mesalamine in maintaining remission. No definite conclusions can be drawn as to
      the efficacy of fibre and herbal medicinal products in IBD patients due to the
      low number of studies and the lack of randomized controlled trials that replicate
      the results obtained in the individual studies conducted so far. Thus, further,
      well-designed studies are needed to address the real role of these therapeutic
      options in the management of both FBD and IBD. LINKED ARTICLES: This article is
      part of a themed section on Principles of Pharmacological Research of
      Nutraceuticals. To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

PMID- 27696384
TI  - We can study ultrarare tumors effectively in this day and age, it just takes a
      cooperative approach: The role of dasatinib in assorted indolent sarcomas.

PMID- 27696385
TI  - Evaluation of a population-based approach to familial colorectal cancer.
AB  - As Newfoundland has the highest rate of familial colorectal cancer (CRC) in the
      world, we started a population-based clinic to provide colonoscopic and Lynch
      syndrome (LS) screening recommendations to families of CRC patients based on
      family risk. Of 1091 incident patients 51% provided a family history. Seventy-two
      percent of families were at low or intermediate-low risk of CRC and colonoscopic
      screening recommendations were provided by letter. Twenty-eight percent were at
      high and intermediate-high risk and were referred to the genetic counsellor, but
      only 30% (N = 48) were interviewed by study end. Colonoscopy was recommended more
      frequently than every 5 years in 35% of families. Lower family risk was
      associated with older age of proband but the frequency of screening colonoscopy
      recommendations varied across all age groups, driven by variability in family
      history. Twenty-four percent had a high MMR predict score for a Lynch syndrome
      mutation, and 23% fulfilled the Provincial Program criteria for LS screening. A
      population-based approach in the provision of colonoscopic screening
      recommendations to families at risk of CRC was limited by the relatively low
      response rate. A family history first approach to the identification of LS
      families was inefficient.

PMID- 27696386
TI  - Association of hepcidin-25 with survival after kidney transplantation.
AB  - BACKGROUND: Hepcidin is considered the master regulator of iron homoeostasis.
      Novel hepcidin antagonists have recently been introduced as potential treatment
      for iron-restricted anaemia. Meanwhile, serum hepcidin has been shown to be
      positively associated with cardiovascular disease and inversely with acute kidney
      injury. These properties may lead to contrasting effects, especially in renal
      transplant recipients (RTR), which are prone to cardiovascular diseases and graft
      failure. To date, the role of serum hepcidin in RTR is unknown. We, therefore,
      prospectively determined the association of serum hepcidin with risk of graft
      failure, cardiovascular mortality and all-cause mortality in RTR. MATERIALS AND
      METHODS: Serum hepcidin was assessed in an extensively phenotyped RTR cohort by
      dual-monoclonal sandwich ELISA specific immunoassay. Statistical analyses were
      performed using univariate linear regression followed by stepwise backward linear
      regression. Cox proportional hazard regression models were performed to determine
      prospective associations. RESULTS: We included 561 RTR (age 51 +/- 12 years).
      Mean haemoglobin (Hb) was 8.6 +/- 1.0 mM. Median [IQR] serum hepcidin was 7.2
      [3.2-13.4] ng/mL. Mean estimated glomerular filtration rate was 47 +/- 16
      mL/min/1.73 m2 . In univariate Cox regression analyses, serum hepcidin was not
      associated with risk of graft failure, cardiovascular mortality or all-cause
      mortality. Notably, after adjustment for high sensitivity C-reactive protein and
      ferritin, serum hepcidin became negatively associated with all-cause mortality
      (hazard ratio 0.89; 95% confidence interval 0.80-0.99, P = 0.03). CONCLUSIONS: In
      this study, we did not find an association between serum hepcidin and outcomes,
      that is graft failure, cardiovascular mortality or all-cause mortality. Based on
      our results, it is questionable whether serum hepcidin may be used to predict a
      beneficial effect of hepcidin antagonists.

PMID- 27696387
TI  - Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis
      complex.
AB  - OBJECTIVE: Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic
      disorder with highly variable expression. The most common neurologic
      manifestation of TSC is epilepsy, which affects approximately 85% of patients,
      63% of whom develop treatment-resistant epilepsy. Herein, we evaluate the
      efficacy, safety, and tolerability of cannabidiol (CBD), a nonpsychoactive
      compound derived from the marijuana plant, as an adjunct to current antiepileptic
      drugs in patients with refractory seizures in the setting of TSC. METHODS:
      Eighteen of the 56 patients who have enrolled in our current expanded-access
      study of cannabidiol for patients with treatment-resistant epilepsy carry a
      diagnosis of TSC. After an initial baseline period of 1 month, patients began
      treatment with CBD. The initial dose of 5 mg/kg/day was increased by 5 mg/kg/day
      every week up to a maximum dose of 50 mg/kg/day, if tolerated. Weekly seizure
      frequencies, percent change in seizure frequencies, and responder rates were
      calculated during the 2nd, 3rd, 6th, 9th, and 12th month of treatment with CBD.
      RESULTS: The median weekly seizure frequency during the baseline period was 22.0
      (interquartile range [IQR] 14.8-57.4), which decreased to 13.3 (IQR 5.1-22.1)
      after 3 months of treatment with cannabidiol. The median percent change in total
      weekly seizure frequency was -48.8% (IQR -69.1% to -11.1%) after 3 months of
      treatment. The 50% responder rates over the course of the study were 50%, 50%,
      38.9%, 50%, and 50% after 2, 3, 6, 9, and 12 months of treatment with CBD,
      respectively. In patients taking clobazam concurrently with CBD (n = 12), the
      responder rate after 3 months of treatment was 58.3%, compared to 33.3% in
      patients not taking clobazam (n = 6). Twelve (66.7%) of 18 patients in this study
      experienced at least one adverse event thought possibly related to CBD; the most
      common adverse events were drowsiness (n = 8, 44.4%), ataxia (n = 5, 27.8%), and
      diarrhea (n = 4, 22.2%). SIGNIFICANCE: Although double-blind, placebo-controlled
      trials are still necessary, these findings suggest that cannabidiol may be an
      effective and well-tolerated treatment option for patients with refractory
      seizures in TSC.

PMID- 27696388
TI  - The kerion: an angry tinea capitis.
AB  - Tinea capitis has a high incidence with a global changing pathogen distribution,
      making this condition a public health concern around the world. As the infection
      is initially asymptomatic, it is easily spread. Moreover, it is present in many
      fomites, including hairbrushes, pillows, and bedding. Prompt recognition and
      treatment is necessary for kerion, an inflammatory subtype characterized by
      tender boggy plaques with purulent drainage. Kerion is usually associated with
      infection by zoophilic dermatophytes, although other sources have been described.
      Treatment for this severe form of dermatophytic infection can be challenging. In
      addition to the use of topical treatments, oral administration of griseofulvin,
      terbinafine, itraconazole, or fluconazole is often required. Griseofulvin, the
      first-line treatment, may not completely eradicate pathogen colonization of the
      host and may contribute to reinfection and prevalence of infective but
      asymptomatic carriers. This review highlights new agents that are being evaluated
      for the treatment of kerion and typical tinea capitis, enhanced diagnostic
      criteria, and a grading system for kerion evaluation.

PMID- 27696389
TI  - Improvements in hepatitis B virus screening before rituximab therapy: A community
      based, safety-net hospital experience.
AB  - BACKGROUND: Individuals with chronic hepatitis B virus infection (HBV) or
      previously resolved HBV are at increased risk of HBV exacerbation or reactivation
      when they receive treatment with anti-CD20 monoclonal antibodies (against B
      lymphocyte antigen cluster of differentiation 20 [CD20], an activated
      glycosylated phosphoprotein) like rituximab (RTX). The objective of the current
      study was to evaluate the rates of appropriate HBV screening before patients
      started receiving RTX, at the initiation of HBV treatment, and during HBV flares
      among an underserved safety-net population. METHODS: In total, 244 consecutive
      adults who received treatment with RTX from 2006 to 2015 at an urban safety-net
      hospital were evaluated to determine appropriate HBV screening (HBV surface
      antigen [HBsAg] and HBV total core antibody [HBcAb]) before starting RTX. The
      initiation of prophylactic antiviral therapy and the development of HBV flares
      after starting RTX were evaluated. Predictors of appropriate HBV screening were
      evaluated using multivariate logistic regression models. RESULTS: Most patients
      were women (52.7%; n = 128) and of Hispanic ethnicity (30.7%; n = 74). Before
      starting RTX, 60.5% (n = 147) of patients received appropriate HBV screening. The
      HBV screening rates before RTX improved from 14.7% (2006-2009) to 74.7% (2010
      2012), and to 87.1% (2013-2015; P < .01. Two of 7 (28.6%) HBsAg-positive patients
      who did not receive antiviral therapy experienced HBV flares and 1 died, and 2 of
      27 patients (7.4%) HBcAb-positive/HBsAg-negative patients who did not receive
      antiviral therapy experienced HBV reactivation. No patient-specific or disease
      specific predictors of receiving HBV screening before RTX therapy were
      identified. CONCLUSIONS: Among adults receiving RTX therapy in a single community
      based hospital system, HBV screening rates were suboptimal, and 28.6% of HBsAg
      positive patients and 7.4% of HBsAg-negative/HBcAb-positive patients who did not
      receive antiviral treatment experienced HBV reactivation or flare. Cancer
      2017;123:650-656. (c) 2016 American Cancer Society.

PMID- 27696390
TI  - Assessment of the family environment in pediatric neurodisability: a state-of-the
      art review.
AB  - The importance of the family environment for the development of children with
      neurodisabilities is undisputed. The objective of this study is to describe how
      family environment has been measured in research on families of children with
      neurodisabilities, in order to support researchers and clinicians to select
      appropriate methods for use. A three-step approach was used and 13 measures of
      family environment were identified within 77 studies. Five measures were used
      most commonly across a majority of studies (n=50). The measures varied
      considerably in terms of theoretical background, content, subscales, and
      populations for which they were developed and validated. These measures were used
      with considerable variability between studies and with a limited range of
      research respondents, most typically the child's mother. Challenges,
      opportunities, and suggestions on how to improve the application of family
      environment measures in research are discussed.

PMID- 27696392
TI  - Interleukin-17 as a factor linking the pathogenesis of psoriasis with metabolic
      disorders.
AB  - Psoriasis is a systemic disease with numerous concomitant metabolic disorders.
      Apparently, T-helper 17 lymphocytes and interleukin (IL)-17 constitute an
      important element linking those disorders. The role of IL-17 has been confirmed
      by numerous studies, although it remains not completely understood, and the study
      results are controversial. Based on the studies performed so far, it is assumed
      that IL-17 contributes to development of atherosclerosis by means of: stimulation
      of production of proinflammatory compounds; induction of apoptosis of endothelial
      cells and heart muscle cells; stimulation of von Willebrand factor production;
      and induction of the matrix metalloproteinase-9 (atherosclerotic plaque rupture).
      On the other hand, IL-17 may exert protective activity due to inhibition of
      proatherogenic interferon-gamma and vascular cell adhesion molecule-1, and
      production of type I collagen by smooth muscle cells. The role of IL-17 in the
      pathogenesis of obesity is as important as other proinflammatory cytokines. On
      the other hand, its deficiency increases diet-induced obesity and accelerates
      adipose tissue accumulation. Although the role of IL-17A in the pathogenesis of
      metabolic disorders in humans remains controversial, introduction of anti-IL-17A
      treatments brings hope that development of metabolic disorders in patients with
      psoriasis may be inhibited.

PMID- 27696391
TI  - Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome
      negative acute lymphoblastic leukemia in the era of minimal residual disease.
AB  - BACKGROUND: The introduction of novel prognostic factors such as minimal residual
      disease (MRD) and genomic profiling has led to the reevaluation of the role of
      cytogenetics and other conventional factors in risk stratification for acute
      lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline
      cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome
      negative ALL who were receiving frontline chemotherapy. Three hundred thirty
      patients (77%) were treated with hyperfractionated cyclophosphamide, vincristine,
      doxorubicin, and dexamethasone-based regimens, and 98 (23%) were treated with the
      augmented Berlin-Frankfurt-Munster regimen. RESULTS: The median age was 40 years
      (range, 13-86 years). One hundred eighty-six patients (43%) had diploid
      cytogenetics, 32 (7%) had complex cytogenetics (defined as >= 5 chromosomal
      abnormalities), 27 (6%) had low hypodiploidy/near-triploidy (Ho-Tr), 24 (6%) had
      high hyperdiploidy, and 24 (6%) had a mixed-lineage leukemia (MLL) rearrangement.
      Patients with an MLL rearrangement, Ho-Tr, or a complex karyotype had
      significantly worse relapse-free survival (RFS) and overall survival (OS) than
      the diploid group. According to a multivariate analysis including all the
      baseline characteristics and MRD status, Ho-Tr and a complex karyotype were
      independent predictive factors for worse RFS and OS. Furthermore, survival among
      all cytogenetic groups was similar, regardless of the treatment received.
      CONCLUSIONS: A complex karyotype and Ho-Tr are adverse prognostic factors for
      adults with ALL independently of the MRD status. These findings suggest that
      pretreatment cytogenetics remain a valuable prognostic tool in this population.
      Cancer 2017;123:459-467. (c) 2016 American Cancer Society.

PMID- 27696393
TI  - Increased protoporphyrin IX accumulation does not improve the effect of
      photodynamic therapy for actinic keratosis: a randomized controlled trial.
AB  - BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is
      highly effective for treating actinic keratosis (AK) on the face/scalp, but less
      effective on the extremities. Insufficient accumulation of protoporphyrin IX
      (PpIX) may cause these inferior efficacy rates. However, it is possible to
      increase PpIX accumulation by extending the MAL application time and/or
      pretreating the skin with curettage. OBJECTIVES: To investigate whether increased
      PpIX accumulation improves the effect of MAL-PDT for AKs in a randomized intra
      individual study. METHODS: Twenty-two patients with 533 AKs on both hands were
      treated with MAL-PDT. To obtain different concentrations of PpIX, four
      symmetrical areas on each patient were randomly allocated to different regimens:
      (i) 3-h MAL application without prior curettage (3hC-); (ii) 3 h with curettage
      (3hC+); (iii) 21 h without curettage (21hC-); and (iv) 21 h with curettage
      (21hC+). Treatment efficacy was evaluated after 3 months, whereas PpIX
      fluorescence, pain and erythema were assessed during and after PDT. RESULTS:
      Extended MAL application with and without curettage increased PpIX accumulation
      significantly compared with the standard 3hC+ regimen (P = 0.001 and P = 0.002,
      respectively). However, the median total clearance rates did not improve
      accordingly: 3hC+ (55.0%), 21hC- (55.0%) and 21hC+ (53.6%). Conversely,
      insufficient PpIX accumulation in the 3hC- regimen led to a significantly lower
      clearance rate (33.3%) than the other regimens (P < 0.045). Furthermore, pain and
      erythema were correlated to PpIX accumulation. CONCLUSIONS: Increased PpIX
      accumulation does not improve the effect of MAL-PDT for AKs on the hands, but
      leads to worse adverse events. Different strategies are needed to improve PDT on
      the extremities.

PMID- 27696394
TI  - MicroRNA-494 Activation Suppresses Bone Marrow Stromal Cell-Mediated Drug
      Resistance in Acute Myeloid Leukemia Cells.
AB  - Acute myeloid leukemia (AML) is not sensitive to chemotherapy partially because
      of the protection of AML cells by mesenchymal stromal cells (MSCs). Our previous
      studies found that MSCs protected AML cells from apoptosis through the c-Myc
      dependent pathway. However, the mechanism by which MSCs regulate c-Myc in AML
      cells is still unknown. To elucidate the mechanism, we performed microRNA array
      analysis of AML cell lines and validated by TaqMan realtime PCR. The results
      showed that the expression of microRNA-494 (miR-494) in AML cells after coculture
      with MSCs was downregulated. Reporter gene analysis confirmed miR-494 as one of
      the regulators of c-Myc. In the coculture system, activation of miR-494 in AML
      cells suppressed proliferation and induced apoptosis of AML cells in vitro. After
      addition of mitoxantrone to the coculture system, the proliferation of AML cells
      with miR-494 activation was suppressed more than that of control cells. After
      subcutaneous injection of AML cell lines in combination with MSC, tumor growth
      was suppressed in mice injected with miR-494-overexpressing AML cells. The rate
      of tumor formation was even lower after mitoxantrone treatment in the miR-494
      overexpressing group. Moreover, miR-494 activation resulted in a decrease of
      leukemic cell counts in peripheral blood (PB) and bone marrow, and prolonged
      survival in mice injected with miR-494-overexpressing AML cellls and MSCs
      compared to the control mice. Our results indicate that miR-494 suppresses drug
      resistance in AML cells by downregulating c-Myc through interaction with MSCs and
      that miR-494 therefore is a potential therapeutic target. J. Cell. Physiol. 232:
      1387-1395, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696396
TI  - Atypical effects of incorporated surfactants on stability and dissolution
      properties of amorphous polymeric dispersions.
AB  - OBJECTIVES: To understand the impact of ionic and non-ionic surfactants on the
      dissolution and stability properties of amorphous polymeric dispersions using
      griseofulvin (GF) as a model for poorly soluble drugs. METHODS: Solid dispersions
      of the poorly water-soluble drug, griseofulvin (GF) and the polymers,
      poly(vinylpyrrolidone) (PVP) and poly(2-hydroxypropyl methacrylate) (PHPMA), have
      been prepared by spray drying and bead milling and the effect of the ionic and
      non-ionic surfactants, namely sodium dodecyl sulphate (SDS) and Tween-80, on the
      physico-chemical properties of the solid dispersions studied. KEY FINDINGS: The X
      ray powder diffraction data and hot-stage microscopy showed a fast re
      crystallisation of GF. While dynamic vapour sorption (DVS) measurements indicated
      an increased water uptake, slow dissolution rates were observed for the solid
      dispersions incorporating surfactants. The order by which surfactants free
      dispersions were prepared seemed critical as indicated by DVS and thermal
      analysis. Dispersions prepared by milling with SDS showed significantly better
      stability than spray-dried dispersions (drug remained amorphous for more than 6
      months) as well as improved dissolution profile. CONCLUSIONS: We suggest that
      surfactants can hinder the dissolution by promoting aggregation of polymeric
      chains, however that effect depends mainly on how the particles were prepared.

PMID- 27696395
TI  - A phase 2 study of nanoparticle albumin-bound paclitaxel plus nedaplatin for
      patients with advanced, recurrent, or metastatic cervical carcinoma.
AB  - BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and nedaplatin
      (NDP) are used for the treatment of patients with cervical cancer. However, to
      the authors' knowledge, the use of this combination regimen among patients with
      advanced, recurrent, or metastatic cervical cancer has rarely been reported.
      METHODS: Patients with pathologically confirmed, stage IVB (FIGO staging 2009),
      recurrent or metastatic cervical cancer were eligible. Nab-paclitaxel at a dose
      of 175 mg/m2 plus NDP at a dose of 80 mg/m2 was administered intravenously every
      3 weeks. The primary endpoint of the current study was the objective response
      rate (ORR). The secondary endpoints were progression-free survival, overall
      survival, and safety. RESULTS: A total of 27 patients were included (5 with late
      stage and 22 with recurrent or metastatic disease). The mean age of the patients
      was 48.26 +/- 9.21 years. Of these 27 patients, 25 had squamous cell carcinoma
      (92.6%). A total of 26 patients completed 92 cycles of chemotherapy, with an
      average of 3.4 cycles per patient. The ORR was 50.0% (13 of 26 patients). The
      overall survival was 16.6 months (95% confidence interval, 12.6-20.6 months) and
      the progression-free survival was 9.1 months (95% confidence interval, 2.4-15.8
      months).The ORR of patients with an interval of >12 months from receipt of prior
      chemotherapy was significantly higher than that of those with a shorter interval
      (71.4% vs 25.0%; P = .034). The most common adverse effects reported were
      myelosuppression, gastrointestinal reactions, fatigue, and peripheral neuropathy.
      The incidence of grade 3 neutropenia was 33.3% (adverse effects were graded on a
      scale from 0 to 4 according to the National Cancer Institute's Common Terminology
      Criteria for Adverse Events [version 3.0]). The incidence of grade 3
      thrombocytopenia and anemia was 7.4% and 18.5%, respectively. The incidence of
      grade 1 to 2 peripheral neuropathy was reported to be as high as 51.9%. No case
      of hypersensitivity was observed. CONCLUSIONS: The combination of nab-paclitaxel
      plus NDP for the treatment of patients with late-stage, recurrent, or metastatic
      cervical cancer appears to be active and tolerable. Cancer 2017;123:420-425. (c)
      2016 American Cancer Society.

PMID- 27696397
TI  - In vitro skin permeation of sinigrin from its phytosome complex.
AB  - OBJECTIVES: Sinigrin is a major glucosinolate present in plants of the
      Brassicaceae family. Recently, sinigrin and its phytosome formulations have been
      investigated for its wound-healing actions, by our research group. The aim of
      this study was to demonstrate sinigrin drug release from its phytosome complex
      and also to determine whether the phytosome complex enhances the delivery of
      sinigrin into the skin when compared to free sinigrin. METHODS: In vitro Franz
      cell diffusion studies were performed on human abdominal skin. The morphology of
      the phytosome complex was examined by transmission electron microscopy. The in
      vitro drug release was determined using dialysis sacks. KEY FINDINGS: The in
      vitro drug release indicated a controlled and sustained release of sinigrin from
      the phytosome complex. Tape stripping results showed that the sinigrin-phytosome
      complex (0.5155 MUg/ml) statistically significantly enhanced the delivery of
      sinigrin into the stratum corneum-epidermis when compared to the free sinigrin
      (0.0730 MUg/ml). CONCLUSIONS: These results suggested the possibility of
      utilizing sinigrin-phytosome complex, to optimally deliver sinigrin to the skin
      which can be further used for various skin-related diseases including wound
      healing.

PMID- 27696398
TI  - Suicide on Death Row.
AB  - Despite the level of supervision of inmates on death row, their suicide rate is
      higher than both the male prison population in the United States and the
      population of males over the age of 14 in free society. This study presents
      suicide data for death row inmates from 1978 through 2010. For the years 1978
      through 2010, suicide rates on death row were higher than that for the general
      population of males over the age of 15 and for state prisons for all but 2 years.

PMID- 27696400
TI  - Retraction.
AB  - : Retraction: "Notch-1 down-regulation by curcumin is associated with the
      inhibition of cell growth and the induction of apoptosis in pancreatic cancer
      cells" by Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar FH. The above article,
      published in Wiley Online Library (wileyonlinelibrary.com), has been retracted by
      agreement amongst the journal Editor in Chief, Fadlo R. Khuri; Wiley Periodicals,
      Inc.; and the American Cancer Society following an investigation by Wayne State
      University into the research activities of the first and last authors. The
      investigation found clear evidence that the 4-lane Rb bands for Figures 4A, 4B,
      5D, and 6D are duplicated and manipulated and re-labeled. The investigation
      further found no evidence that the 4-lane Rb bands correspond to the assays above
      them. In addition, the investigation found clear evidence that the 2-lane Rb
      bands for Figure 4C are duplicated and manipulated and re-labeled Rb bands. The
      investigation further found no evidence that the 2-lane Rb bands correspond to
      the "supershift" assays they accompany. There is no evidence that these loading
      control assays were run at all. The investigation also found that the beta-actin
      bands image in Figure 3D and 5A are re-labeled and manipulated copies of the beta
      actin bands image in Figure 3C of Int J Cancer. 2006 Apr 15;118(8):1930-6.
      Finally, the investigation found that the beta-actin bands image in Figure 6A is
      a re-labeled and manipulated copy of Figure 3A of Int J Cancer. 2006 Apr
      15;118(8):1930-6, representing two very different experiments. The investigation
      committee concluded that this undermined the scientific basis of the publication,
      that no credible replacement data were available, and advised that the
      publication should be retracted. REFERENCES: Wang, Z., Zhang, Y., Banerjee, S.,
      Li, Y. and Sarkar, F. H. (2006), Notch-1 down-regulation by curcumin is
      associated with the inhibition of cell growth and the induction of apoptosis in
      pancreatic cancer cells. Cancer, 106: 2503-2513. doi: 10.1002/cncr.21904 Wang,
      Z., Zhang, Y., Banerjee, S., Li, Y. and Sarkar, F. H. (2006), Inhibition of
      nuclear factor kappab activity by genistein is mediated via Notch-1 signaling
      pathway in pancreatic cancer cells. Int. J. Cancer, 118: 1930-1936. doi:
      10.1002/ijc.21589.

PMID- 27696399
TI  - Toluene inhalation in adolescent rats reduces flexible behaviour in adulthood and
      alters glutamatergic and GABAergic signalling.
AB  - Toluene is a commonly abused inhalant that is easily accessible to adolescents.
      Despite the increasing incidence of use, our understanding of its long-term
      impact remains limited. Here, we used a range of techniques to examine the acute
      and chronic effects of toluene exposure on glutameteric and GABAergic function,
      and on indices of psychological function in adult rats after adolescent exposure.
      Metabolomics conducted on cortical tissue established that acute exposure to
      toluene produces alterations in cellular metabolism indicative of a glutamatergic
      and GABAergic profile. Similarly, in vitro electrophysiology in Xenopus oocytes
      found that acute toluene exposure reduced NMDA receptor signalling. Finally, in
      an adolescent rodent model of chronic intermittent exposure to toluene (10 000
      ppm), we found that, while toluene exposure did not affect initial learning, it
      induced a deficit in updating that learning when response-outcome relationships
      were reversed or degraded in an instrumental conditioning paradigm. There were
      also group differences when more effort was required to obtain the reward;
      toluene-exposed animals were less sensitive to progressive ratio schedules and to
      delayed discounting. These behavioural deficits were accompanied by changes in
      subunit expression of both NMDA and GABA receptors in adulthood, up to 10 weeks
      after the final exposure to toluene in the hippocampus, prefrontal cortex and
      ventromedial striatum; regions with recognized roles in behavioural flexibility
      and decision-making. Collectively, our data suggest that exposure to toluene is
      sufficient to induce adaptive changes in glutamatergic and GABAergic systems and
      in adaptive behaviour that may underlie the deficits observed following
      adolescent inhalant abuse, including susceptibility to further drug-use.

PMID- 27696401
TI  - Retraction.
AB  - : Retraction: "Cisplatin-induced antitumor activity is potentiated by the soy
      isoflavonen genistein in BxPC-3 pancreatic tumor xenografts" by Mohammad RM,
      Banerjee S, Li Y, Aboukameel A, Kucuk O, Sarkar FH. The above article, published
      in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement
      amongst the journal Editor in Chief, Fadlo R. Khuri; Wiley Periodicals, Inc.; and
      the American Cancer Society following an investigation by Wayne State University
      into the research activities of the second and last authors. The investigation
      found clear evidence that the 4-lane Rb bands for Figure 3A and Figure 4C are
      duplicated, manipulated, and re-labeled Rb bands. The investigation found no
      evidence that the 4-lane Rb bands correspond to the assays above them. The
      investigation further found that the 4-lane beta-actin bands image in Figure 3B
      is a manipulated and re-labeled copy of the same beta-actin bands image in Figure
      5A of Int J Cancer. 2006 Apr 15;118(8):1930-6. The investigation committee
      concluded that this undermined the scientific basis of the publication, that no
      credible replacement data were available, and advised that the publication should
      be retracted. REFERENCES: Mohammad, R. M., Banerjee, S., Li, Y., Aboukameel, A.,
      Kucuk, O. and Sarkar, F. H. (2006), Cisplatin-induced antitumor activity is
      potentiated by the soy isoflavone genistein in BxPC-3 pancreatic tumor
      xenografts. Cancer, 106: 1260-1268. doi: 10.1002/cncr.21731 Wang, Z., Zhang, Y.,
      Banerjee, S., Li, Y. and Sarkar, F. H. (2006), Inhibition of nuclear factor
      kappab activity by genistein is mediated via Notch-1 signaling pathway in
      pancreatic cancer cells. Int. J. Cancer, 118: 1930-1936. doi: 10.1002/ijc.21589.

PMID- 27696402
TI  - Erratum.

PMID- 27696403
TI  - Retraction.
AB  - : Retraction: "Genistein enhances the effect of epidermal growth factor receptor
      tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell
      lung cancer cell lines" by Gadgeel SM, Ali S, Philip PA, Wozniak A, Sarkar FH.
      The above article, published in Wiley Online Library (wileyonlinelibrary.com),
      has been retracted by agreement amongst the journal Editor in Chief, Fadlo R.
      Khuri; Wiley Periodicals, Inc.; and the American Cancer Society following an
      investigation by Wayne State University into the research activities of the
      second and last authors. The investigation found that the Western blot images of
      Figures 4A, 4B, and 4C were re-ordered and manipulated to misrepresent the
      results. The investigation committee concluded that this undermined the
      scientific basis of the publication, that no credible replacement data were
      available, and advised that the publication should be retracted. REFERENCE:
      Gadgeel, S. M., Ali, S., Philip, P. A., Wozniak, A. and Sarkar, F. H. (2009),
      Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase
      inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell
      lines. Cancer, 115: 2165-2176. doi: 10.1002/cncr.24250.

PMID- 27696404
TI  - Retraction.
AB  - : Retraction: "Response to dual blockade of epidermal growth factor receptor
      (EGFR) and cyclooxygenase-2 in nonsmall cell lung cancer may be dependent on the
      EGFR mutational status of the tumor" by Gadgeel SM, Ali S, Philip PA, Ahmed F,
      Wozniak A, Sarkar FH. The above article, published in Wiley Online Library
      (wileyonlinelibrary.com), has been retracted by agreement amongst the journal
      Editor in Chief, Fadlo R. Khuri; Wiley Periodicals, Inc.; and the American Cancer
      Society following an investigation by Wayne State University into the research
      activities of the second and last authors. The investigation found that masking
      and other manipulations altered the appearance of certain Western blots published
      in Figure 1A beyond "cosmetic" changes, and that these alterations changed the
      results. The investigation further found that there was masking in p-EGFR bands
      of the H3255 cells in Figure 5A, and found no evidence that the "data" published
      as non-expressed COX-2 and Akt in the H1650 cells in Figures 5A and 5B are
      anything other than plain gray boxes. The investigation committee concluded that
      this undermined the scientific basis of the publication, that no credible
      replacement data were available, and advised that the publication should be
      retracted. REFERENCE: Gadgeel, S. M., Ali, S., Philip, P. A., Ahmed, F., Wozniak,
      A. and Sarkar, F. H. (2007), Response to dual blockade of epidermal growth factor
      receptor (EGFR) and cycloxygenase-2 in nonsmall cell lung cancer may be dependent
      on the EGFR mutational status of the tumor. Cancer, 110: 2775-2784. doi:
      10.1002/cncr.23100.

PMID- 27696405
TI  - Effects of Hovenia dulcis Thunb. extract and methyl vanillate on atopic
      dermatitis-like skin lesions and TNF-alpha/IFN-gamma-induced chemokines
      production in HaCaT cells.
AB  - OBJECTIVES: Here, we hypothesized that Hovenia dulcis branch extract (HDB) and
      its active constituents ameliorates 2,4-dinitrochlorobenzene-induced atopic
      dermatitis (AD)-like skin lesions by modulating the T helper Th1/Th2 balance in
      NC/Nga mice and TNF-alpha- and IFN-gamma-induced production of thymus and
      activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in
      HaCaT cells. METHODS: HaCaT cells were stimulated by TNF-alpha/IFN-gamma in the
      presence of HDB and its constituents. TARC and MDC were measured by ELISA and RT
      PCR. For the in-vivo study, oral feeding of HDB was performed for 5 weeks with
      2,4-dinitrochlorobenzene (DNCB) treatment every other day. The efficacy of HDB on
      parameters of DNCB-induced AD was evaluated morphologically, physiologically and
      immunologically. KEY FINDINGS: In-vitro studies showed that HDB and its
      constituents suppressed TNF-alpha/IFN-gamma-induced production of TARC and MDC in
      HaCaT cells by inhibiting MAPK signalling. In-vivo studies showed that HDB
      regulated immunoglobulin (Ig) E and immunoglobulin G2a (IgG2a) levels in serum
      and the expression of mRNA for Th1- and Th2-related mediators in skin lesions.
      Histopathological analyses revealed reduced epidermal thickness and reduced
      infiltration of skin lesions by inflammatory cells. CONCLUSION: These results
      suggest that HDB inhibits AD-like skin diseases by regulating Th1 and Th2
      responses in NC/Nga mice and in HaCaT cells.

PMID- 27696406
TI  - Inhibition of human glioma cell proliferation by altered Bax/Bcl-2-p53 expression
      and apoptosis induction by Rhaponticum carthamoides extracts from transformed and
      normal roots.
AB  - OBJECTIVE: The objective of this study was to determine the cytotoxic effect and
      apoptotic activity of Rhaponticum carthamoides transformed root (TR) and root of
      soil-grown plant (NR) extracts in a human glioma primary cells. The effect of
      these root extracts on cell cycle arrest, mitochondrial membrane potential
      (DeltaPsim) and expression levels of apoptosis-related genes (Bcl-2, Bax and p53)
      were also examined. METHODS: Cytotoxic activity of root extracts was evaluated by
      MTT assay. Apoptosis and cell cycle were determined by flow cytometry. Expression
      levels of apoptosis-related gene were analysed by RT-PCR and Western blotting.
      DeltaPsim was examined by the use of JC-1 reagent. KEY FINDINGS: Rhaponticum
      carthamoides root extracts inhibit cell growth and induce apoptosis in a dose
      dependent manner in human glioma cells. The root extracts were found to up
      regulate the pro-apoptotic Bax protein and down-regulate the anti-apoptotic Bcl-2
      protein, consequently increasing the ratios of Bax/Bcl-2 protein levels.
      Moreover, an increase of the p53 protein level and reduction of DeltaPsim in
      glioma cells were observed after treatment with NR and TR extracts. CONCLUSION:
      The results of this study may offer a new insight into the potential anticancer
      activity of R. carthamoides root extracts.

PMID- 27696407
TI  - Effects of extracts from Corylopsis coreana Uyeki (Hamamelidaceae) flos on
      xanthine oxidase activity and hyperuricemia.
AB  - OBJECTIVES: This study aims to investigate xanthine oxidase (XO) inhibitory
      activity and antihyperuricemic effects of Corylopsis coreana Uyeki flos extracts
      and the phytochemicals contained therein. METHODS: Ethanolic extracts of the
      plant were prepared, and the extraction process was optimized with respect to
      flavonoid content and XO inhibitory activity. The optimized ethanolic extract was
      tested for its XO inhibitory activity and antihyperuricemic effects in potassium
      oxonate-induced hyperuricemic mice. KEY FINDINGS: The 80% ethanolic extract
      showed the highest total flavonoid content and in-vitro XO inhibitory activity.
      In-vivo studies demonstrated that the optimized 80% ethanolic extract could
      inhibit hepatic XO activity and significantly alleviate hyperuricemia at a
      relatively low oral dose (50 mg/kg) in mice. Additionally, an in-vitro enzyme
      inhibition study showed that phytochemicals such as bergenin, isosalipurposide,
      quercetin and quercitrin may be the key constituents responsible for the observed
      antihyperuricemic effects of the extract. CONCLUSIONS: This study is the first
      report on the XO inhibitory and antihyperuricemic effects of C. coreana Uyeki
      flos extract, which can be therapeutically applied in treating hyperuricemia and
      gout.

PMID- 27696408
TI  - Widespread brain transcriptome alterations underlie the neuroprotective actions
      of dietary saffron.
AB  - Dietary saffron has shown promise as a neuroprotective intervention in clinical
      trials of retinal degeneration and dementia and in animal models of multiple CNS
      disorders, including Parkinson's disease. This therapeutic potential makes it
      important to define the relationship between dose and protection and the
      mechanisms involved. To explore these two issues, mice were pre-conditioned by
      providing an aqueous extract of saffron (0.01% w/v) as their drinking water for
      2, 5 or 10 days before administration of the parkinsonian neurotoxin MPTP (50
      mg/kg). Five days of saffron pre-conditioning provided the greatest benefit
      against MPTP-induced neuropathology, significantly mitigating both loss of
      functional dopaminergic cells in the substantia nigra pars compacta (p < 0.01)
      and abnormal neuronal activity in the caudate-putamen complex (p < 0.0001). RNA
      microarray analysis of the brain transcriptome of mice pre-conditioned with
      saffron for 5 days revealed differential expression of 424 genes. Bioinformatics
      analysis identified enrichment of molecular pathways (e.g. adherens junction,
      TNFR1 and Fas signaling) and expression changes in candidate genes (Cyr61, Gpx8,
      Ndufs4, and Nos1ap) with known neuroprotective actions. The apparent biphasic
      nature of the dose-response relationship between saffron and measures of
      neuroprotection, together with the stress-inducible nature of many of the up
      regulated genes and pathways, lend credence to the idea that saffron, like
      various other phytochemicals, is a hormetic stimulus, with functions beyond its
      strong antioxidant capacity. These findings provide impetus for a more
      comprehensive evaluation of saffron as a neuroprotective intervention.

PMID- 27696409
TI  - Brefeldin A-inhibited guanine nucleotide exchange protein 3 is localized in
      lysosomes and regulates GABA signaling in hippocampal neurons.
AB  - ADP-ribosylation factor (ARF) family of guanine-nucleotide-binding (G) proteins
      regulates organelle biogenesis, structure and trafficking. The functions of ARF
      proteins are tightly controlled by guanine nucleotide exchange factors (GEFs)
      containing a conserved SEC7 domain. Based on sequence similarity to brefeldin A
      inhibited guanine nucleotide exchange protein (BIG)/GBF of the Arf-GEF family, we
      recently identified BIG3 as a novel ARF GEF protein with a non-functional
      catalytic motif in the SEC7 domain. BIG3 is mainly expressed in pancreatic islets
      and brain. In the islets, depletion of BIG3 increases insulin and glucagon
      secretion because of enhanced biogenesis of insulin and glucagon granules in the
      absence of BIG3. Here, we investigate BIG3 functions in the brain, in particular
      its regulation of neurotransmitter release in hippocampal neurons from wild-type
      and BIG3 knockout mice. In hippocampal neurons, BIG3 is mainly localized in
      lysosomes, and its depletion selectively impairs inhibitory synaptic
      transmission. Our finding provides novel insights for a cell-specific function of
      BIG3 in regulating neurotransmission.

PMID- 27696410
TI  - Adult ciliary neurotrophic factor receptors help maintain facial motor neuron
      choline acetyltransferase expression in vivo following nerve crush.
AB  - Exogenous ciliary neurotrophic factor (CNTF) administration promotes the survival
      of motor neurons in a wide range of models. It also increases the expression of
      the critical neurotransmitter enzyme choline acetyltransferase (ChAT) by in vitro
      motor neurons, likely independent of its effects on their survival. We have used
      the adult mouse facial nerve crush model and adult-onset conditional disruption
      of the CNTF receptor alpha (CNTFRalpha) gene to directly examine the in vivo
      roles played by endogenous CNTF receptors in adult motor neuron survival and ChAT
      maintenance, independent of developmental functions. We have previously shown
      that adult activation of the CreER gene construct in floxed CNTFRalpha mice
      depletes this essential receptor subunit in a large subset of motor neurons (and
      all skeletal muscle, as shown in this study) but has no effect on the survival of
      intact or lesioned motor neurons, indicating that these adult CNTF receptors play
      no essential survival role in this model, in contrast to their essential role
      during embryonic development. Here we show that this same CNTFRalpha depletion
      does not affect ChAT labeling in nonlesioned motor neurons, but it significantly
      increases the loss of ChAT following nerve crush. The data suggest that, although
      neither motor neuron nor muscle CNTF receptors play a significant, nonredundant
      role in the maintenance of ChAT in intact adult motor neurons, the receptors
      become essential for ChAT maintenance when the motor neurons are challenged by
      nerve crush. Therefore, the data suggest that the receptors act as a critical
      component of an endogenous neuroprotective mechanism. J. Comp. Neurol. 525:1206
      1215, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696411
TI  - Simulating Stable Isotope Ratios in Plumes of Groundwater Pollutants with
      BIOSCREEN-AT-ISO.
AB  - BIOSCREEN is a well-known simple tool for evaluating the transport of dissolved
      contaminants in groundwater, ideal for rapid screening and teaching. This work
      extends the BIOSCREEN model for the calculation of stable isotope ratios in
      contaminants. A three-dimensional exact solution of the reactive transport from a
      patch source, accounting for fractionation by first-order decay and/or sorption,
      is used. The results match those from a previously published isotope model but
      are much simpler to obtain. Two different isotopes may be computed, and dual
      isotope plots can be viewed. The dual isotope assessment is a rapidly emerging
      new approach for identifying process mechanisms in aquifers. Furthermore,
      deviations of isotope ratios at specific reactive positions with respect to
      "bulk" ratios in the whole compound can be simulated. This model is named
      BIOSCREEN-AT-ISO and will be downloadable from the journal homepage.

PMID- 27696412
TI  - A cross-sectional study of patient and provider perception of "cure" as a goal of
      cancer surgery.
AB  - BACKGROUND AND OBJECTIVE: Patients with advanced cancer often misperceive the
      purpose and likely effectiveness of cancer treatments. The aim of this study was
      to characterize patient and provider perceptions in the setting of surgery for
      potentially curable cancer. METHODS: One hundred and six patient-surgeon dyads
      were surveyed about their expectations for upcoming surgery. Items scored using a
      Likert scale were compared using the Wilcoxon signed-rank test. RESULTS: Patients
      and surgeons reported excellent communication and shared decision-making.
      Patients more often than surgeons perceived that surgery was "Likely" or "Very
      Likely" to cure their cancer (86.0% vs. 72.0%, P = 0.011), extend their lives
      (94.0% vs. 82.0%, P = 0.007), and relieve cancer-related symptoms (65.0% vs.
      35.0%, P < 0.001). Patients less often felt that surgery would be associated with
      complications (33.0% vs. 48.0%, P = 0.016). Over half (53.9%) of patients
      believed that they were more likely to experience surgical cancer cure compared
      with someone else with the same diagnosis while 70.8% of surgeons declared a
      patient's relative chances of surgical cure "the same." CONCLUSIONS: Patients
      with resectable lung and gastrointestinal cancers have more optimistic
      perceptions about the outcomes of an upcoming surgery than their surgeons, even
      in a setting of good communication and shared decision-making. J. Surg. Oncol.
      2016;114:677-683. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696413
TI  - Genetic consequences of Quaternary climatic oscillations in the Himalayas:
      Primula tibetica as a case study based on restriction site-associated DNA
      sequencing.
AB  - The effects of Quaternary climatic oscillations on the demography of organisms
      vary across regions and continents. In taxa distributed in Europe and North
      America, several paradigms regarding the distribution of refugia have been
      identified. By contrast, less is known about the processes that shaped the
      species' spatial genetic structure in areas such as the Himalayas, which is
      considered a biodiversity hotspot. Here, we investigated the phylogeographic
      structure and population dynamics of Primula tibetica by combining genomic
      phylogeography and species distribution models (SDMs). Genomic data were obtained
      for 293 samples of P. tibetica using restriction site-associated DNA sequencing
      (RADseq). Ensemble SDMs were carried out to predict potential present and past
      distribution ranges. Four distinct lineages were identified. Approximate Bayesian
      computation analyses showed that each of them have experienced both expansions
      and bottlenecks since their divergence, which occurred during or across the
      Quaternary glacial cycles. The two lineages at both edges of the distribution
      were found to be more vulnerable and responded in different ways to past climatic
      changes. These results illustrate how past climatic changes affected the
      demographic history of Himalayan organisms. Our findings highlight the
      significance of combining genomic approaches with environmental data when
      evaluating the effects of past climatic changes.

PMID- 27696414
TI  - Proof-of-principle study of a novel cervical screening and triage strategy:
      Computer-analyzed cytology to decide which HPV-positive women are likely to have
      >=CIN2.
AB  - A challenge in implementation of sensitive HPV-based screening is limiting
      unnecessary referrals to colposcopic biopsy. We combined two commonly recommended
      triage methods: partial HPV typing and "reflex" cytology, evaluating the
      possibility of automated cytology. This investigation was based on 1,178
      exfoliated cervical specimens collected during the enrollment phase of The Study
      to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED, Oklahoma
      City, OK). We chose a colposcopy clinic population to maximize number of
      outcomes, for this proof-of-principle cross-sectional study. Residual aliquots of
      PreservCyt were HPV-typed using Linear Array (LA, Roche Molecular Systems,
      Pleasanton, CA). High-risk HPV typing data and cytologic results (conventional
      and automated) were used jointly to predict risk of histologically defined
      >=CIN2. We developed a novel computer algorithm that uses the same optical
      scanning features that are generated by the FocalPoint Slide Profiler (BD,
      Burlington, NC). We used the Least Absolute Shrinkage and Selection Operator
      (LASSO) method to build the prediction model based on a training dataset (n =
      600). In the validation set (n = 578), for triage of all HPV-positive women, a
      cytologic threshold of >=ASC-US had a sensitivity of 0.94, and specificity of
      0.30, in this colposcopy clinic setting. When we chose a threshold for the
      severity score (generated by the computer algorithm) that had an equal
      specificity of 0.30, the sensitivity was 0.91. Automated cytology also matched
      >=ASC-US when partial HPV typing was added to the triage strategy, and when we re
      defined cases as >=CIN3. If this strategy works in a prospective screening
      setting, a totally automated screening and triage technology might be possible.

PMID- 27696415
TI  - Grape by-product extracts against microbial proliferation and lipid oxidation: a
      review.
AB  - The wine industry is responsible for the production of million tons of waste,
      such as grape skin, stalk, sludge and seeds, which can be considered inexpensive
      sources of phenolic compound owing to incomplete extraction during wine
      production. Phenolic compounds, also called polyphenols, comprise the most
      abundant bioactive compounds in grape and are recognized by their antioxidant and
      antimicrobial potential. Because of their functional properties, extracts
      obtained from grape wastes, which are rich in phenolic compounds, can be employed
      in the development of many products, ranging from medical to food applications,
      decreasing the growth of spoilage and pathogenic microorganisms and inhibiting
      lipid oxidation. These characteristics are motivating the research for
      alternative sources of natural antioxidant and antimicrobial agents, aimed at
      decreasing the use of artificial additives, which have been associated with some
      toxic effects. This article provides a review of the use of grape by-product
      extracts and their bioactive compounds as natural antioxidant and antimicrobial
      agents in food products. (c) 2016 Society of Chemical Industry.

PMID- 27696416
TI  - The ART of mating: alternative reproductive tactics and mating success in a nest
      guarding fish.
AB  - Behavioural observations in the field of male Mediterranean damselfish Chromis
      chromis were combined with molecular analyses, using bi-parentally and maternally
      inherited markers, to investigate reproductive success patterns of alternative
      reproductive tactics (ARTs) in terms of number of eggs sired and number of
      females contributing to each nest. Cuckoldry was observed in every nest sampled,
      with at least two and up to seven sneaker males per nest. The nesting male,
      however, always significantly fertilized the greater number of eggs (on average
      49%) in each clutch, whereas each sneaker fertilized around 7% of the clutch. The
      average number of females whose eggs were fertilized by nesting males was 6.76
      (range 2-13), while each sneaker on average fertilized the eggs of 1.74 (range 1
      8) females. Using this sibship reconstruction, some of the factors involved in
      the regulation of the dynamic equilibrium of reproductive success were
      investigated between the two ARTs shown by C. chromis males. Results show that
      the sneakers' reproductive success was positively linked to egg clutch size; the
      density of individuals in the nesting area negatively affected the size of egg
      clutches; the rate of defence behaviours performed by nesting males negatively
      influenced the number of females contributing to each nest.

PMID- 27696418
TI  - Impact of a novel synbiotic supplementation during gestation and lactation on
      immune responses in the Swiss albino mice offspring.
AB  - BACKGROUND: Prebiotics from various regularly consumed cereals and novel
      substrates are currently being utilised as functional foods. The aim of this
      study was to determine the effect of synbiotic, formulated with prebiotic
      extracted from natural resources like green gram (Vigna radiata) along with
      probiotic Lactobacillus rhamnosus GG (LGG) in modulating immune responses in the
      offspring when supplemented during gestation and lactation. RESULTS: Synbiotic
      supplementation was effective in improving cell mediated immunity and humoral
      immunity among F0 dams. Among F1 pups (F1 Syn + and F1 Syn-), synbiotic
      supplementation showed significantly heightened (P < 0.05) splenocyte
      proliferation, increased interleukin-10, interferon gamma and interleukin-17
      responses, leucocyte phagocytic ability and increased secretory-immunoglobulin A.
      However, four-fold increase in IgG titres to Hepatitis-B vaccine was observed
      only in those mice that were supplemented with synbiotic postweaning (F1 Syn+).
      CONCLUSION: Synbiotic supplementation to pregnant dams affected the offspring's
      cellular and mucosal immunity favorably. However, IgG response to Hepatitis-B
      vaccine was influenced positively only when the supplementation was extended to
      the offsprings in the post weaning period. (c) 2016 Society of Chemical Industry.

PMID- 27696417
TI  - Apoplastic recognition of multiple candidate effectors from the wheat pathogen
      Zymoseptoria tritici in the nonhost plant Nicotiana benthamiana.
AB  - The fungus Zymoseptoria tritici is a strictly apoplastic, host-specific pathogen
      of wheat leaves and causal agent of septoria tritici blotch (STB) disease. All
      other plants are considered nonhosts, but the mechanism of nonhost resistance
      (NHR) to Z. tritici has not been addressed previously. We sought to develop
      Nicotiana benthamiana as a system to study NHR against Z. tritici. Fluorescence
      microscopy and quantitative reverse transcription polymerase chain reactions were
      used to establish the interaction between Z. tritici and N. benthamiana.
      Agrobacterium-mediated transient expression was used to screen putative Z.
      tritici effector genes for recognition in N. benthamiana, and virus-induced gene
      silencing (VIGS) was employed to determine the role of two receptor-like kinases
      (RLKs), NbBAK1 and NbSOBIR1, in Z. tritici effector recognition. Numerous Z.
      tritici putative effectors (14 of 63 tested) induced cell death or chlorosis in
      N. benthamiana. For most, phenotypes were light-dependent and required effector
      secretion to the leaf apoplastic space. Moreover, effector-induced host cell
      death was dependent on NbBAK1 and NbSOBIR1. Our results indicate widespread
      recognition of apoplastic effectors from a wheat-infecting fungal pathogen in a
      taxonomically distant nonhost plant species presumably by cell surface immune
      receptors. This suggests that apoplastic recognition of multiple nonadapted
      pathogen effectors may contribute to NHR.

PMID- 27696419
TI  - Immune-affinity monolithic array with chemiluminescent detection for mycotoxins
      in barley.
AB  - BACKGROUND: Mycotoxins are produced by fungi as secondary metabolites. They often
      multi-contaminate food and feed commodities posing a health risk to humans and
      animals. Fast and easy multiplex screening could be thought as a useful tool for
      detection of multi-contaminated food and feed commodities. RESULTS: A highly
      sensitive immune-affinity monolithic arrays for detecting the mycotoxins
      zearalenone, deoxynivalenol, T-2 toxin, HT-2 toxin, aflatoxins, ochratoxin A, and
      fumonisin B1 were fabricated using UV induced co-polymerisation. The mycotoxin
      antibodies firstly reacted with functional monomer to form antibody/functional
      monomer bio-conjugates. Subsequently, the antibody/functional monomer bio
      conjugates co-polymerised with cross-linker to form mycotoxins immune-affinity
      arrays. With optimal fabrication conditions, all mycotoxin immune-affinity
      monolithic arrays exhibited a linear response spanning three orders of magnitude.
      And the immune-affinity monolithic array has a low detection limit and has a good
      uniformity (intra-assay CV, and inter-assay CV both <8%). CONCLUSION: The
      fabricated mycotoxin immune-affinity monolithic arrays were proved as a
      sensitive, stable and economical tool in real food samples detection. Moreover,
      the mycotoxin immune-affinity monolithic arrays would be able to minimise
      manipulation steps: add samples and enzyme labelled mycotoxins, and detect CL
      signals. (c) 2016 Society of Chemical Industry.

PMID- 27696420
TI  - Plasticity in mitochondrial cristae density allows metabolic capacity modulation
      in human skeletal muscle.
AB  - KEY POINTS: In human skeletal muscles, the current view is that the capacity for
      mitochondrial energy production, and thus endurance capacity, is set by the
      mitochondria volume. However, increasing the mitochondrial inner membrane surface
      comprises an alternative mechanism for increasing the energy production capacity.
      In the present study, we show that mitochondrial inner membranes in leg muscles
      of endurance-trained athletes have an increased ratio of surface per
      mitochondrial volume. We show a positive correlation between this ratio and whole
      body oxygen uptake and muscle fibre mitochondrial content. The results obtained
      in the present study help us to understand modulation of mitochondrial function,
      as well as how mitochondria can increase their oxidative capacity with increased
      demand. ABSTRACT: Mitochondrial energy production involves the movement of
      protons down a large electrochemical gradient via ATP synthase located on the
      folded inner membrane, known as cristae. In mammalian skeletal muscle, the
      density of cristae in mitochondria is assumed to be constant. However, recent
      experimental studies have shown that respiration per mitochondria varies.
      Modelling studies have hypothesized that this variation in respiration per
      mitochondria depends on plasticity in cristae density, although current evidence
      for such a mechanism is lacking. In the present study, we confirm this hypothesis
      by showing that, in human skeletal muscle, and in contrast to the current view,
      the mitochondrial cristae density is not constant but, instead, exhibits
      plasticity with long-term endurance training. Furthermore, we show that
      frequently recruited mitochondria-enriched fibres have significantly increased
      cristae density and that, at the whole-body level, muscle mitochondrial cristae
      density is a better predictor of maximal oxygen uptake rate than muscle
      mitochondrial volume. Our findings establish an elevating mitochondrial cristae
      density as a regulatory mechanism for increasing metabolic power in human
      skeletal muscle. We propose that this mechanism allows evasion of the trade-off
      between cell occupancy by mitochondria and other cellular constituents, as well
      as improved metabolic capacity and fuel catabolism during prolonged elevated
      energy requirements.

PMID- 27696422
TI  - Rate of new findings in diagnostic office bronchoscopy.
AB  - OBJECTIVES: Awake Flexible Tracheobronchoscopy (FTB) is an alternative to rigid
      bronchoscopy or sedated flexible bronchoscopy and allows an awake examination of
      the tracheobronchial tree. We hypothesized that the ability to perform office
      bronchoscopy as the need arises during a clinic visit would lead to a high rate
      of previously undiagnosed and clinically relevant findings. This study reports
      the rate and nature of such findings for this procedure at our institution. STUDY
      DESIGN: Retrospective chart review. METHODS: The records of 127 adult patients
      evaluated at the voice and swallowing disorders clinic between June of 2012 and
      January of 2015 were reviewed. New findings were defined as new pathology
      visualized during FTB exam that was not previously diagnosed by means of other
      diagnostic modalities. RESULTS: A total of 233 scope procedures (84 transnasal
      bronchoscopies and 149 tracheoscopies) were reviewed, 232 of which were completed
      and one of which was incomplete due to severe subglottic stenosis. New,
      clinically relevant findings were seen in 57% of transnasal bronchoscopies (48 of
      84) and 21% of tracheoscopies (32 of 149). All of these findings provided
      additional information directing workup or resulted in a change in patient
      management. CONCLUSION: Office-based evaluation of the tracheobronchial tree
      yields a high rate of new findings. In our study, office bronchoscopy had a 57%
      rate of new findings and was performed without complications. The utility of
      tracheoscopy was also apparent in its ability to quickly and safely examine the
      trachea, with a 21% rate of new findings. LEVEL OF EVIDENCE: 4. Laryngoscope,
      127:1376-1380, 2017.

PMID- 27696421
TI  - Response of saliva Na/K ratio to changing Na supply of lactating cows under
      tropical conditions.
AB  - BACKGROUND: Factorial determination of the sodium (Na) requirement of heat
      stressed lactating cows is hindered by accurate estimates of the Na losses
      through sweat. Direct studies, therefore, may be needed requiring information on
      the time course of healthy animals to become Na depleted and the subsequent rate
      of repletion. The rate of Na depletion and subsequent rate of Na repletion with
      two levels of dietary Na to lactating dairy cows housed under tropical conditions
      were investigated using the salivary Na/K. RESULTS: The 12 lactating cows
      (salivary Na/K ratio 14.6) rapidly developed clinical signs of Na deficiency,
      including pica, polyuria and polydipsia, reduced body weight and reduced milk
      yield when fed a low-Na ration (0.33 g kg-1 dry matter (DM)) for 3 weeks.
      Deficiency symptoms were associated with a rapid decrease in salivary Na/K ratio
      to <4.3 from 7 to 21 days. Subsequent repletion of the cows with NaCl to a ration
      concentration of 1.1 or 1.6 g Na kg-1 DM for 5 weeks did not restore salivary
      Na/K ratio to values of >6. CONCLUSION: A daily Na intake of heat-stressed
      lactating cows to a ration intake of 1.6 g Na kg-1 DM was insufficient to restore
      Na deficiency. One week was sufficient to deplete heat-stressed lactating cows of
      Na, allowing for rapid dose-response studies utilizing the salivary Na/K ratio as
      a parameter for Na status of cows under tropical conditions. (c) 2016 Society of
      Chemical Industry.

PMID- 27696423
TI  - Microparticle surface layering through dry coating: impact of moisture content
      and process parameters on the properties of orally disintegrating tablets.
AB  - OBJECTIVES: The aim of this study was to investigate the influence of process
      parameters during dry coating on particle and dosage form properties upon varying
      the surface adsorbed moisture of microcrystalline cellulose (MCC), a model
      filler/binder for orally disintegrating tablets (ODTs). METHODS: The moisture
      content of MCC was optimised using the spray water method and analysed using
      thermogravimetric analysis. Microproperty/macroproperty assessment was
      investigated using atomic force microscopy, nano-indentation, scanning electron
      microscopy, tablet hardness and disintegration testing. KEY FINDINGS: The results
      showed that MCC demonstrated its best flowability at a moisture content of 11.2%
      w/w when compared to control, comprising of 3.9% w/w moisture. The use of the
      composite powder coating process (without air) resulted in up to 80% increase in
      tablet hardness, when compared to the control. The study also demonstrated that
      surface adsorbed moisture can be displaced upon addition of excipients during dry
      processing circumventing the need for particle drying before tabletting.
      CONCLUSIONS: It was concluded that MCC with a moisture content of 11% w/w
      provides a good balance between powder flowability and favourable ODT
      characteristics.

PMID- 27696424
TI  - Yeast and bacteria from ensiled high moisture maize grains as potential
      mitigation agents of fumonisin B1.
AB  - BACKGROUND: Fumonisin B1 (FB1 ) is a mycotoxin produced by several Fusarium
      species and is a very common contaminant of maize-based food and feed throughout
      the world. The selection and use of FB1 -degrading microorganisms appears as a
      promising alternative to cope with the problem of toxicity towards humans and
      livestock. High moisture maize grain silage, which is based on natural maize
      fermentation, could be an interesting reservoir of such microorganisms. RESULTS:
      Using an in vitro simulated silage model with FB1 naturally contaminated grains,
      we demonstrated a significant raw decrease in FB1 during ensiling process
      ascribed to biodegradation mechanisms. A panel of 98 bacteria and yeasts were
      isolated from this matrix and selected for their ability to use FB1 as the sole
      source of C and N. For nine of them, the ability to degrade FB1 in vitro was
      evidenced. Notably, two bacteria identified as Lactobacillus sp. were highlighted
      for their efficient FB1 -degrading capacity and production of hydrolysed FB1 as
      intermediate degradation metabolite. CONCLUSION: Fermentation of high moisture
      maize grain contaminated with FB1 leads to a significant reduction of the toxin
      and allows the isolation of FB1 -degrading microorganisms that could further be
      used as FB1 decontaminating agents. (c) 2016 Society of Chemical Industry.

PMID- 27696425
TI  - Nutrient profiles of the hybrid grape cultivar 'Isabel' during berry maturation
      and ripening.
AB  - BACKGROUND: The hybrid grape cultivar 'Isabel' (Vitis labrusca * V. vinifera) is
      widely grown in the Black Sea region of Turkey and constitutes an important part
      of the diet of its inhabitants. Phenological and ampelographic studies of the
      grape have previously been performed, but there are no data concerning nutrient
      composition. Its nutrient content needs to be investigated to ascertain its
      potential economic and nutritional uses in the region. RESULTS: The
      concentrations (range, g kg-1 fresh weight) of major soluble sugars (fructose
      2.08-79.70; glucose 3.71-66.74) increased and those of organic acids (tartaric
      acid 0.05-6.60; malic acid 2.38-9.92) decreased in the skin and pulp during
      ripening. The major fatty acid was linoleic acid in the skin (50.13), pulp
      (18.11) and seed (704), while the main minerals (dry weight) were potassium (2.70
      19.70), followed by phosphorus (0.53-3.40) and calcium (0.42-5.90) in the parts.
      CONCLUSION: Berry maturation and ripening significantly influenced the
      concentrations of sugars and organic acids the most in the skin and pulp, but did
      not significantly affect the concentrations of fatty acids and minerals in the
      'Isabel' grape. Our findings also suggest an optimal harvest time in terms of
      levels of the nutrients. (c) 2016 Society of Chemical Industry.

PMID- 27696426
TI  - Hybrid Minimal Core Streptavidin-Obelin as a Versatile Reporter for
      Bioluminescence-based Bioassay.
AB  - Ca2+ -regulated photoprotein obelin was genetically fused with a minimum-sized
      core streptavidin. Hybrid protein (SAV-OL) was produced by bacterial expression
      and applied as a specific bioluminescent probe in diverse solid-phase assays. The
      obtained results clearly demonstrate specific activity of each domain indicating
      its proper folding with favorable space orientation. SAV-OL has been shown to be
      a much more sensitive label than the chemical conjugate of a full-length
      streptavidin with obelin.

PMID- 27696427
TI  - Proteomic analysis of peel browning of 'Nanguo' pears after low-temperature
      storage.
AB  - BACKGROUND: Postharvest ripening of the 'Nanguo' pear (Pyrus ussuriensis Maxim.)
      can be impeded by low-temperature storage. However, pears after long-term
      refrigeration are prone to peel browning when returned to room temperature
      conditions. This study investigated the browning mechanism of 'Nanguo' pear
      stored at a low temperature by analysing the differentially expressed proteins
      between healthy fruit and fruit with peel browning. RESULTS: The results showed
      that 181 proteins underwent statistically significant changes. A categorisation
      of the disparately accumulated proteins was performed using gene ontology
      annotation. The results showed that the 'metabolic process', 'cellular process',
      'catalytic activity', and 'binding' proteins were the most affected after low
      temperature storage. Further analysis revealed that the differentially expressed
      proteins, which are related to peel browning, are primarily involved in the
      phenylpropanoid pathway, linoleic acid pathways, fatty acid biosynthesis pathway,
      glutathione metabolism pathway, photosynthesis pathway, oxidative phosphorylation
      pathway, and glycolysis pathway. CONCLUSION: This study reveals that there are
      variations in key proteins in 'Nanguo' pear after low-temperature storage, and
      the identification of these proteins will be valuable in future functional
      genomics studies, as well as provide protein resources that can be used in the
      efforts to improve pear quality. (c) 2016 Society of Chemical Industry.

PMID- 27696429
TI  - Effect of phytosanitary irradiation and methyl bromide fumigation on the
      physical, sensory, and microbiological quality of blueberries and sweet cherries.

PMID- 27696428
TI  - Transglutaminase-catalyzed amination of pea protein peptides using the biogenic
      amines histamine and tyramine.
AB  - BACKGROUND: Biogenic amines (BAs) are produced by the enzymatic decarboxylation
      of amino acids, and are well-known for their toxicity to humans. This study
      describes a new method using microbial transglutaminase (MTGase) to covalently
      link BAs such as histamine (HIS) and tyramine (TYR) to the glutamine residues of
      alcalase-hydrolyzed pea protein (PPH). RESULTS: The incubation of PPH and HIS and
      TYR in the presence of MTGase at 37  degrees C led to the formation of
      conjugates, as determined by liquid chromatography, after derivatization with
      dansyl chloride. Seventy-six % of HIS and 65% of TYR were covalently incorporated
      to PPH by MTGase. The incubation of PPH and TYR in the presence of MTGase
      exhibited a 52% DPPH radical scavenging activity at 10 mg mL-1 . Conjugation via
      MTGase improved the antioxidant status by reducing lipid peroxidation.
      CONCLUSION: This study emphasizes that the application of MTGase can effectively
      reduce histamine and tyramine content while simultaneously enhancing
      antioxidative capacity of PPH. (c) 2016 Society of Chemical Industry.

PMID- 27696430
TI  - Using Diurnal Temperature Signals to Infer Vertical Groundwater-Surface Water
      Exchange.
AB  - Heat is a powerful tracer to quantify fluid exchange between surface water and
      groundwater. Temperature time series can be used to estimate pore water fluid
      flux, and techniques can be employed to extend these estimates to produce
      detailed plan-view flux maps. Key advantages of heat tracing include cost
      effective sensors and ease of data collection and interpretation, without the
      need for expensive and time-consuming laboratory analyses or induced tracers.
      While the collection of temperature data in saturated sediments is relatively
      straightforward, several factors influence the reliability of flux estimates that
      are based on time series analysis (diurnal signals) of recorded temperatures.
      Sensor resolution and deployment are particularly important in obtaining robust
      flux estimates in upwelling conditions. Also, processing temperature time series
      data involves a sequence of complex steps, including filtering temperature
      signals, selection of appropriate thermal parameters, and selection of the
      optimal analytical solution for modeling. This review provides a synthesis of
      heat tracing using diurnal temperature oscillations, including details on optimal
      sensor selection and deployment, data processing, model parameterization, and an
      overview of computing tools available. Recent advances in diurnal temperature
      methods also provide the opportunity to determine local saturated thermal
      diffusivity, which can improve the accuracy of fluid flux modeling and sensor
      spacing, which is related to streambed scour and deposition. These parameters can
      also be used to determine the reliability of flux estimates from the use of heat
      as a tracer.

PMID- 27696431
TI  - Cloning of the Blue Ghost (Phausis reticulata) Luciferase Reveals a Glowing
      Source of Green Light.
AB  - In the southern Appalachian area of the United States, the Phausis reticulata
      firefly, commonly known as the "Blue Ghost," performs a unique display of
      bioluminescence. Adult male organisms are observed darting rapidly along paths
      and riverbeds in dark forests producing long-lasting and mesmerizing bluish-white
      luminous streaks. Starting with eighteen adult male firefly lanterns, we used a
      reverse transcriptase and rapid amplification of cDNA ends (RACE) approach to
      clone the 1635 base pair open reading frame of the P. reticulata luc gene
      corresponding to a 545 residue protein. Expression of the recombinant luciferase
      protein in Escherichia coli and characterization studies revealed the true color
      of the light emission to be green (lambdamax = 552 nm), strongly suggesting that
      the field observations result from a Purkinje shift. While the P. reticulata
      luciferase amino acid sequence is 74.3% identical to the North American Photinus
      pyralis luciferase, we were surprised to find that it was 88.4% and 87.7%
      identical to luciferases from C. ruficollis and D. axillaris both native to
      mainland Japan. Phylogenetic analysis confirmed the close relationship of the
      three enzymes that is surprising given the great distance between their natural
      habitats and the inability of the Japanese fireflies to produce bright
      bioluminescence.

PMID- 27696432
TI  - The prognostic role of systemic inflammation in patients undergoing resection of
      colorectal liver metastases: C-reactive protein (CRP) is a strong negative
      prognostic biomarker.
AB  - BACKGROUND AND OBJECTIVES: Systemic inflammation has been associated with poor
      survival in several tumor types, but has been less extensively studied in
      resectable metastatic disease. The aim of the present study was to evaluate the
      prognostic role of CRP in colorectal cancer patients with liver metastases (CRLM)
      compared to conventional tumor- and patient-related clinicopathological features
      as well as other indicators of the systemic inflammatory response (SIR). METHODS:
      A multinational retrospective study of 492 CRLM patients undergoing potentially
      curative resection of liver metastases between 1999 and 2009. Clinicopathological
      findings and the SIR markers CRP, hypoalbuminemia, and their combined Glasgow
      Prognostic Score (GPS) were analyzed. RESULTS: Multivariate analysis showed that
      preoperative CRP >10 mg/L was a strong predictor of compromised survival (HR =
      1.72, 95%CI 1.84-2.50, P < 0.01). Patients with CRP <=10 mg/L had a median
      survival of 4.27 years compared to only 47 days in patients with CRP >=30 mg/L (P
      < 0.01). Similarly, increased GPS was independently predictive of poor survival
      (HR 1.67, 95%CI 1.22-2.27, P < 0.01), but hypoalbuminemia alone did not have
      significant prognostic value. CONCLUSIONS: CRP alone is a strong prognostic
      factor, following curative resection of colorectal liver metastases and should be
      taken into consideration when selecting treatment strategies in CRLM patients. J.
      Surg. Oncol. 2016;114:895-899. (c) 2016 2016 Wiley Periodicals, Inc.

PMID- 27696433
TI  - How risk perception shapes collective action intentions in repressive contexts: A
      study of Egyptian activists during the 2013 post-coup uprising.
AB  - Social psychological research has overlooked collective action in repressive
      contexts, where activists face substantial personal risks. This paper examines
      the social psychological processes motivating activists to engage in collective
      action in risky contexts. We investigate the idea that perceived risks due to
      government sanctions can galvanize action through fuelling anger, shaping
      efficacy beliefs, and increasing identification with the movement. We also argue
      that anger, efficacy, and identification motivate action intentions directly and
      indirectly through reducing the personal importance activists attach to these
      risks. We tested our hypotheses within a sample of Egyptian activists (N = 146)
      from two protest movements who protested against Morsi's government and the
      military interventions, respectively, during the 2013 anticoup uprising. In line
      with our hypotheses, the perceived likelihood of risks was positively associated
      with anger and identity consolidation efficacy and positively predicted action
      intentions indirectly through these variables. Risk was also associated with
      increased political efficacy, but only among antimilitary protesters. Anger and
      political efficacy predicted action intentions directly and indirectly through
      reduced risk importance. Results also highlighted differential significance of
      emotional and instrumental motives for the two protest movements. We discuss
      directions for future research on the motivators of collective action in
      repressive contexts.

PMID- 27696434
TI  - Sonographic diagnosis of partial versus complete molar pregnancy: A reappraisal.
AB  - PURPOSE: To assess the prospective sonographic diagnosis of molar pregnancy and
      compare sonographic features of complete versus partial molar pregnancy. METHODS:
      This institutional review board--approved retrospective chart review conducted
      between 2001 and 2011 identified 70 women with a histopathologic diagnosis of
      molar pregnancy and with available sonograms. Clinical data, images, and reports
      were reviewed, and features enumerated by radiologists blinded to the final
      diagnosis. RESULTS: Mean age of patients was 30.5 +/- 7.0 (SD) years (range, 16
      49 years) with a mean gravidity of 3.2 +/- 2.3 (SD) (range 1-11). Mean
      gestational age was 74.0 +/- 19.1 day (range 39-138) and serum beta-human
      chorionic gonadotropin was 131 +/- 156 mIU/ml (range 447-662,000). Pathologic
      results showed 48 partial and 22 complete molar pregnancies. Sonographically,
      partial moles more commonly showed a yolk sac (56.3% versus 0%, p < 0.0001),
      fetal pole (62.5% versus 4.6%, p < 0.0001), fine septa within the sac (25.0%
      versus 4.6%, p = 0.05), and normal (31.3% versus 0%, p = 0.002) or minimally
      cystic placenta (27.1% versus 4.6%, p = 0.49), while complete moles had larger
      gestational sacs (612 versus 44 mm, p = 0.005), were more often avascular on
      color Doppler imaging (45.5% versus 18.8%, p = 0.02), had more often abnormal
      tissue in the uterus (82.6% versus 20.8%, p < 0.0001) and placental masses (86.9%
      versus 16.7%, p < 0.0001), and were more often diagnosed prospectively (86.4%
      versus 41.7%, p = 0.0005). CONCLUSIONS: Complete molar pregnancy is associated
      with marked cystic changes and mass formation and is often diagnosed
      sonographically. Partial molar pregnancy often presents with minor cystic changes
      of the placenta and remains underdiagnosed sonographically. However, correct
      prospective diagnosis was made more frequently in this study than in older
      reports, perhaps due to improved spatial resolution of sonographic equipment. (c)
      2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:72-78, 2017.

PMID- 27696435
TI  - Comparison of two apheresis systems for autologous stem cell collections in
      pediatric oncology patients.
AB  - BACKGROUND: Peripheral stem cell collections can be challenging in the pediatric
      population and respective experience is limited. Since February 2015 our
      institution is utilizing the new Spectra Optia (Optia) apheresis device, which
      has replaced the former COBE Spectra (COBE) device. As a quality initiative we
      collected and compared collection efficiency (CE2) and other collection variables
      between the two devices. STUDY DESIGN AND METHODS: In this retrospective study we
      collected and compared clinical, laboratory, and technical collection data from
      stem cell collection procedures done with the Optia and COBE devices. The
      collected data included patient demographics, precollection peripheral CD34+ cell
      counts, total CD34+ cells collected, complete blood count, electrolytes before
      and after collection, side effects attributed to the collection, total blood
      volumes processed (TBVs), collection times, and calculated CE2 and collection
      ratios. RESULTS: Forty-one collection procedures performed on 29 pediatric
      patients with the Optia device were compared to 41 collections performed on 27
      patients with the COBE device. The TBVs through the Optia device were
      significantly smaller than the COBE (3.9 +/- 0.2 * TBV vs. 5.5 +/- 0.1 * TBV,
      respectively; p < 0.001), requiring significantly less anticoagulant and
      providing similar amounts of stem cells while collection times were significantly
      shorter (mean, 238 +/- 9 min vs. 264 +/- 9 min, respectively; p < 0.05).
      Collections on the Optia caused significantly smaller reductions of plasma
      calcium and magnesium. No significant side effects attributed to the procedure
      were noted. CONCLUSION: Stem cell apheresis with the Optia device in children is
      safe and feasible with smaller blood volumes with shorter collection times.

PMID- 27696437
TI  - 'The deserving': Moral reasoning and ideological dilemmas in public responses to
      humanitarian communications.
AB  - This study investigates everyday moral reasoning in relation to donations and
      prosocial behaviour in a humanitarian context. The discursive analysis focuses on
      the principles of deservingness which members of the public use to decide who to
      help and under what conditions. The study discusses three repertoires of
      deservingness - 'seeing a difference', 'waiting in queues', and 'something for
      nothing' - to illustrate participants' dilemmatic reasoning and to examine how
      the position of 'being deserving' is negotiated in humanitarian crises.
      Discursive analyses of these dilemmatic repertoires of deservingness identify the
      cultural and ideological resources behind these constructions and show how
      humanitarianism intersects and clashes with other ideologies and value systems.
      The data suggest that a neoliberal ideology, which endorses self-gratification,
      materialistic and individualistic ethics, and cultural assimilation of helper and
      receiver play important roles in decisions about humanitarian helping. The study
      argues for the need for psychological research to engage more actively with the
      dilemmas involved in the moral reasoning related to humanitarianism and to
      contextualize decisions about giving and helping within the sociocultural and
      ideological landscape in which the helper operates.

PMID- 27696438
TI  - Are routine ultrasound examinations helpful in the detection of bleeding
      complications following laparoscopic inguinal hernia repair?
AB  - PURPOSE: Intraabdominal bleeding is a dreaded complication after laparoscopic
      transabdominal preperitoneal inguinal hernia repairs. Routine postoperative
      sonographic (US) examination and hemoglobin measurement have been suggested to
      identify bleeding after surgery. We retrospectively assessed the value of these
      tests. METHODS: A total of 995 consecutive patients admitted for laparoscopic
      inguinal hernia repair to a single teaching hospital were analyzed. US
      examinations were performed postoperatively on the operative day to identify
      intraabdominal bleeding. In addition, hemoglobin measurements were obtained on
      the first postoperative day. RESULTS: Postoperative US examinations were
      performed on 971 patients (97.6%). Of these, 945 were examined within 24 hours of
      surgery. Reoperation was necessary in 1.1% (11/995) of the patients because of a
      persistent seroma in five cases, intraabdominal or inguinal bleeding or hematomas
      in five cases, and a trocar hernia in one case. In none of the 11 patients
      requiring reoperation did US examination or hemoglobin measurement indicate acute
      bleeding or hematoma. CONCLUSIONS: Routine postoperative US examination and
      hemoglobin measurement within the first 24 hours of surgery are not suitable for
      identifying patients with intraabdominal bleeding who require a reoperation.
      Instead, US examination and hemoglobin measurement should be part of the patient
      workup when there is a clinical suspicion of a postoperative complication. (c)
      2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:145-149, 2017.

PMID- 27696436
TI  - Radiologic follow-up of untreated enchondroma and atypical cartilaginous tumors
      in the long bones.
AB  - BACKGROUND AND OBJECTIVES: Both enchondroma and atypical cartilaginous tumors
      (ACT) are not considered malignant, so inactive and asymptomatic tumors might not
      need surgery. To the best of our knowledge, this is the first study that has been
      done to evaluate the natural course of conservative-treated enchondroma and ACT
      in the long bones. METHODS: For this retrospective study, we analyzed the results
      of patients in whom we refrained from surgery and only regularly performed
      radiological follow-up of the tumor. Minimal follow-up after initial diagnosis
      was 24 months. RESULTS: Forty-nine patients were included in this study. Eight
      out of forty-nine cases received surgical treatment during follow-up of the
      tumor. The reasons for this surgery were radiologic growth of the tumor in two
      cases, pain in one case, patient request in three cases, another indication for
      surgery in the same limb in two cases. CONCLUSION: In this small series of
      conservatively treated enchondroma and ACT, only 6% of the patients had a medical
      indication for surgery. This study shows that indication for surgery should be
      discussed more thoroughly. Based on our results, we would recommend annual
      radiologic follow-up for asymptomatic enchondroma or ACT in the long bones,
      irrespective of tumor size. J. Surg. Oncol. 2016;114:987-991. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27696440
TI  - Atazanavir increases the plasma concentrations of 1200 mg raltegravir dose.
AB  - Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer
      inhibitor currently marketed at a dose of 400 mg twice-daily (b.i.d.).
      Raltegravir 1200 mg once-daily (q.d.) (investigational q.d. formulation of 2 *
      600 mg tablets; q.d. RAL) was found to be generally well tolerated and non
      inferior to the marketed 400 mg b.i.d. dose at 48 weeks in a phase 3 trial. Since
      raltegravir is eliminated mainly by metabolism via a uridine diphosphate
      glucuronosyltransferase (UGT) 1A1-mediated glucuronidation pathway, co
      administration of UGT1A1 inhibitors may increase the plasma levels of q.d. RAL.
      To assess this potential, the drug interaction of 1200 mg raltegravir using
      atazanavir, a known UGT1A1 inhibitor, was studied. An open-label, randomized, 2
      period, fixed-sequence phase 1 study was performed in adult healthy male and
      female (non-childbearing potential) subjects >= 19 and <= 55 years of age, with a
      body mass index (BMI) >= 18.5 and <= 32.0 kg/m2 . Subjects (n = 14) received a
      single oral dose of 1200 mg raltegravir in period 1. After a washout period of at
      least 7 days, the subjects received oral doses of 400 mg atazanavir q.d. for 9
      consecutive days, with a single oral dose of 1200 mg raltegravir co-administered
      on day 7 of period 2. Serial blood samples were collected for 72 h following
      raltegravir dosing and analysed using a validated bioanalytical method to
      quantify raltegravir plasma concentrations. Co-administration with atazanavir
      yielded GMRs (90% CIs) for raltegravir AUC0-infinity , Cmax and C24 of 1.67
      (1.34, 2.10), 1.16 (1.01, 1.33) and 1.26 (1.08, 1.46), respectively. There was no
      effect of raltegravir on serum total bilirubin. In contrast, atazanavir increased
      the mean bilirubin by up to 200%, an effect that was preserved in the
      atazanavir/raltegravir treatment group. Administration of single q.d. RAL alone
      and co-administered with multiple oral doses of atazanavir were generally well
      tolerated in healthy subjects. The results show that atazanavir increased the PK
      exposure of raltegravir; therefore, co-administration of atazanavir with
      raltegravir q.d. is not recommended. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696439
TI  - Occupational noise exposure, hearing loss, and notched audiograms in the HUNT
      Nord-Trondelag hearing loss study, 1996-1998.
AB  - OBJECTIVES/HYPOTHESIS: To study the prevalence and usefulness of audiometric
      notches in the diagnosis of noise-induced hearing loss (NIHL). STUDY DESIGN:
      Audiograms and data on noise exposure from 23,297 men and 26,477 women, aged 20
      to 101 years, from the Nord-Trondelag Hearing Loss Study, 1996-1998. METHODS: The
      prevalence of four types of audiometric notches (Coles, Hoffman, Wilson) and 4
      kHz notch were computed in relation to occupational noise exposure, age, sex, and
      report of recurrent ear infections. RESULTS: The prevalence of notches in the 3
      to 6 kHz range (Wilson, Hoffman, and Coles) ranged from 50% to 60% in subjects
      without occupational noise exposure, and 60% to 70% in the most occupationally
      noise-exposed men. The differences were statistically significant only for
      bilateral notches. For 4 kHz notches, the prevalence varied from 25% in
      occupationally nonexposed to 35% in the most occupationally exposed men, and the
      differences were statistically significant for both bilateral and unilateral
      notches. For women, the prevalence of notches was lower than in men, especially
      for 4 kHz notches, and the differences between occupationally noise exposed and
      nonexposed were smaller. Recreational exposure to high music was not associated
      with notched audiograms. CONCLUSIONS: The detection of bilateral notches and
      unilateral 4 kHz notches is of some value in diagnosing NIHL, especially in men.
      LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1442-1450, 2017.

PMID- 27696441
TI  - Cost effectiveness of adding nucleic acid testing to hepatitis B, hepatitis C,
      and human immunodeficiency virus screening of blood donations in Zimbabwe.
AB  - BACKGROUND: The aim of this study was to assess the cost effectiveness of
      introducing individual-donation nucleic acid testing (ID-NAT), in addition to
      serologic tests, compared with the exclusive use of serologic tests for the
      identification of hepatitis B virus (HBV), hepatitis C virus (HCV), and human
      immunodeficiency virus (HIV) I and II among blood donors in Zimbabwe. STUDY
      DESIGN AND METHODS: The costs, health consequences, and cost effectiveness of
      adding ID-NAT to serologic tests, compared with serologic testing alone, were
      estimated from a health care perspective using a decision-analytic model.
      RESULTS: The introduction of ID-NAT in addition to serologic tests would lower
      the risk of HBV, HCV, and HIV transmission to 46.9, 0.3, and 2.7 per 100,000
      donations, respectively. ID-NAT would prevent an estimated 25, 6, and 9 HBV, HCV,
      and HIV transfusion-transmitted infections per 100,000 donations, respectively.
      The introduction of this intervention would result in an estimated 212 quality
      adjusted life-years (QALYs) gained. The incremental cost-effectiveness ratio is
      estimated at US$17,774/QALY, a value far more than three times the gross national
      income per capita for Zimbabwe. CONCLUSION: Although the introduction of NAT
      could further improve the safety of the blood supply, current evidence suggests
      that it cannot be considered cost effective. Reducing the test costs for NAT
      through efficient donor recruitment, negotiating the price of reagents, and the
      efficient use of technology will improve cost effectiveness.

PMID- 27696442
TI  - Nociceptin Receptor as a Target to Treat Alcohol Use Disorder: Challenges in
      Advancing Medications Development.

PMID- 27696444
TI  - Investigation of epizootic papillomatosis in bluegill Lepomis macrochirus
      (Rafinesque 1810) using next-generation sequencing.

PMID- 27696443
TI  - Enhanced cellulase recovery without beta-glucosidase supplementation for
      cellulosic ethanol production using an engineered strain and surfactant.
AB  - Recycling cellulases by substrate adsorption is a promising strategy for reducing
      the enzyme cost of cellulosic ethanol production. However, beta-glucosidase has
      no carbohydrate-binding module (CBM). Thus, additional enzymes are required in
      each cycle to achieve a high ethanol yield. In this study, we report a new method
      of recycling cellulases without beta-glucosidase supplementation using
      lignocellulosic substrate, an engineered strain expressing beta-glucosidase and
      Tween 80. The cellulases and Tween 80 were added to an aqueous suspension of
      diluted sulfuric acid/ammonia-treated corncobs in a simultaneous saccharification
      and fermentation (SSF) process for ethanol production. Subsequently, the addition
      of fresh pretreated corncobs to the fermentation liquor and remaining solid
      residue provided substrates with absorbed cellulases for the next SSF cycle. This
      method provided excellent ethanol production in three successive SSF cycles
      without requiring the addition of new cellulases. For a 10% (w/v) solid loading,
      a cellulase dosage of 30 filter paper units (FPU)/g cellulose, 0.5% Tween 80, and
      2 g/L of the engineered strain, approximately 90% of the initial ethanol
      concentration from the first SSF process was obtained in the next two SSF
      processes, with a total ethanol production of 306.27 g/kg corncobs and an enzyme
      productivity of 0.044 g/FPU. Tween 80 played an important role in enhancing
      cellulase recovery. This new enzyme recycling method is more efficient and
      practical than other reported methods. Biotechnol. Bioeng. 2017;114: 543-551. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27696445
TI  - Seroepidemiology of hepatitis A and B and vaccination status in staff at German
      schools for the handicapped.
AB  - This study aims to assess serostatus and vaccination status of hepatitis A and B
      among staff at schools for the handicapped. We also wanted to investigate factors
      associated with serostatus, number of infections with hepatitis A/hepatitis B at
      work, and factors influencing being vaccinated or not. The cross-sectional study
      was carried out between August 2010 and August 2012 at 13 German schools for
      severely handicapped. Data were analyzed using blood samples, vaccination
      documents, and questionnaires. A total of 395 persons participated in our study
      (response: 59.7%), information on 367 could be used for analysis. Two respondents
      have been infected with HAV at work, 53.4% were anti-HAV seropositive.
      Vaccination against hepatitis A was influenced by information about infectious
      diseases before starting to work, level of education, and marital status. One
      person got infected with hepatitis B during work, 53.2% were anti-HBs
      seropositive. Vaccination against hepatitis B depended on perceived burden by
      nursing activities, and vaccination costs being paid by employer. Immunity to
      hepatitis A and B in our sample is insufficient and does not correspond to the
      infectious risks. Two persons got infected with hepatitis A and one person with
      hepatitis B during work at school, indicating an urgent need for preventive
      actions. J. Med. Virol. 89:825-833, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696446
TI  - Determinants of red blood cell transfusion in pediatric trauma patients admitted
      to the intensive care unit.
AB  - BACKGROUND: There are no well-designed prospective studies evaluating transfusion
      practices in pediatric trauma. We sought to describe red blood cell (RBC)
      transfusion practices in trauma patients who were admitted to a pediatric
      intensive care unit (PICU). STUDY DESIGN AND METHODS: This study is a post-hoc
      analysis of a prospective, 6-month observational study in 30 PICUs. We studied a
      total of 580 patients aged less than 18 years who had been admitted to a PICU for
      more than 48 hours, including 95 who were trauma patients. RESULTS: Trauma
      patients more frequently received transfusion before PICU admission (p < 0.001),
      were older (p < 0.0001), and more frequently were mechanically ventilated (p =
      0.05). In the PICU, trauma patients received more transfusions (55% vs. 37%; p <
      0.001), although admission hemoglobin levels were similar in both groups (p =
      0.86). The mean (+/- standard deviation) pretransfusion hemoglobin level in the
      PICU was 9.0 +/- 2.4 g/dL for trauma patients compared with 8.3 +/- 2.4 g/dL for
      nontrauma patients (p = 0.09). Among the trauma patients, transfusion was
      associated with younger age, higher Pediatric Logistic Organ Regression scores,
      mechanical ventilation, bleeding, and transfusion before PICU admission.
      Multivariate regression demonstrated that receiving an RBC transfusion before
      admission was strongly associated with receiving a blood transfusion in the PICU
      (p = 0.008). CONCLUSION: Trauma patients are at high risk for receiving an RBC
      transfusion both before and during their PICU stay, despite a similar transfusion
      threshold compared with nontrauma patients. Transfusion before PICU admission is
      a strong determinant, suggesting ongoing bleeding that will require re
      transfusion. Further studies are needed to evaluate whether a restrictive
      transfusion strategy can safely be considered in these patients.

PMID- 27696447
TI  - Symptomatic treatment of pollen-related allergic rhinoconjunctivitis in children:
      randomized controlled trial.
AB  - BACKGROUND: About 12% of children are affected by allergic rhinoconjunctivitis
      (AR). Although the main symptomatic treatments are intranasal corticosteroids
      (INCS) (daily or on demand) and oral antihistamines, it remains unclear which
      treatment provides the best relief of symptoms. Therefore, this study examines
      whether daily use of INCS is superior to on-demand use or to oral antihistamines
      on demand. METHODS: A single-blinded randomized controlled trial in children
      (aged 6-18 years) with pollen-related AR. Patients received either INCS daily
      (fluticasone propionate), INCS on demand (fluticasone propionate) or oral
      antihistamine on demand (levocetirizine) for 3 months during the grass pollen
      season. A daily online symptom diary on both nose and eye symptoms was completed.
      The primary outcome was the percentage of symptom-free days. RESULTS: A total of
      150 children were randomized. The percentage symptom-free days was in favour of
      INCS on demand (30%) compared with INCS daily (22%), that is 8% difference (95%
      CI -5 to +21%; not significant). The antihistamine on-demand group had 15%
      symptom-free days, that is 7% difference compared to INCS daily (95% CI -6 to
      +19%;, not significant). Patients in the INCS on-demand group used on average 61%
      less fluticasone than patients in the INCS daily group during the study period (P
      < 0.0001). CONCLUSIONS: This trial with three parallel treatment groups shows
      that INCS daily was not superior to INCS on demand or to antihistamine on demand
      regarding the number of symptom-free days. An on-demand INCS strategy has the
      advantage of a lower overall corticosteroid exposure and less costs.

PMID- 27696449
TI  - The disappearance rate and risk assessment of thiacloprid residues in Asian pear
      using liquid chromatography confirmed with tandem mass spectrometry.
AB  - This study was undertaken to quantify the residue levels and propose the
      dissipation kinetics of thiacloprid formulated as suspension concentrate in field
      incurred Asian pears grown under two different open-field conditions. Samples
      were extracted with 20% distilled water in acetonitrile; partitioned with brine
      water and dichloromethane; and purified with a Florisil solid phase extraction
      cartridge. The analyte was identified with an LC ultraviolet detector, and field
      incurred samples were confirmed using LC-MS/MS. The calibration curve was linear
      over the range 0.05-5.0 mg/L with a satisfactory coefficient of determination (R2
      = 0.9994). The limits of detection and limits of quantification (LOQ) were 0.003
      and 0.01 mg/kg, respectively. The recovery rate fortified to blank samples at
      LOQ, 10* LOQ, and the maximum residue limit (MRL) were between 73.7 and 86.2%
      with relative standard deviation <=9.0%. The residual concentrations at both
      sites were considerably lower than the MRL (0.7 mg/kg) set by the Korean Ministry
      of Food Drug Safety, with biological half-lives of 5.0 and 7.4 days, for sites 1
      and 2, respectively. From the pre-harvest residue limit curve, it was predicted
      that if the residues were <1.13 or 1.40 mg/kg 10 days before harvest, the residue
      level would be lower than the MRL during harvest. Risk assessment on day 0 showed
      an acceptable daily intake (%) of 13.0% and 11.0% for sites 1 and site 2,
      respectively, which indicates that the residual amounts are not hazardous to the
      Korean population.

PMID- 27696450
TI  - First report of isolation and characterization of Photobacterium damselae subsp.
      damselae from cage-farmed cobia (Rachycentron canadum).

PMID- 27696451
TI  - Fibrosis is not just fibrosis - basement membrane modelling and collagen
      metabolism differs between hepatitis B- and C-induced injury.
AB  - BACKGROUND: While morphological patterns differ, the molecular phenotype of liver
      fibrosis is considered a stereotypical response to chronic liver injury. However,
      with different cellular triggers and networks regulating fibrosis, the molecular
      responses of the injured liver may not be identical. AIM: To investigate whether
      differences in extracellular matrix (ECM) composition of the liver during
      fibrogenesis in two seemingly similar types of viral hepatitis could be reflected
      by differences in ECM turnover. METHODS: Utilising a cross-sectional design, we
      measured specific ECM protein fragments in plasma from 197 chronic hepatitis B
      (CHB) patients and 403 chronic hepatitis C (CHC) patients matched for
      inflammation grade and fibrosis stage. Markers of matrix metalloprotease degraded
      type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen
      formation (Pro-C3, P4NP7S). RESULTS: P4NP7S, C3M, C4M and C6M were significantly
      elevated in CHB compared to CHC. In contrast, Pro-C3 was significantly elevated
      in CHC compared to CHB. Pro-C3, C3M and C4M were increased in parallel with
      inflammation and fibrosis in both cohorts. C6M and P4NP7S were associated with
      inflammation and fibrosis only in CHC. Basement membrane collagen fragments
      P4NP7S and C4M were significantly higher in matched activity and fibrosis cohorts
      within CHB vs CHC. CONCLUSION: The main parameters to determine extracellular
      matrix biomarker levels are inflammation, fibrosis, and type of viral insult.
      Compared to CHC, CHB appears to induce a higher basement membrane turnover. This
      suggests that there are aetiology-dependent molecular signatures in liver
      fibrosis that could have pathogenic and diagnostic implications.

PMID- 27696448
TI  - Effective fluorescence-guided surgery of liver metastasis using a fluorescent
      anti-CEA antibody.
AB  - BACKGROUND AND OBJECTIVES: Delineation of adequate tumor margins is critical in
      oncologic surgery, particularly in resection of metastatic lesions. Surgeons are
      limited in visualization with bright-light surgery, but fluorescence-guided
      surgery (FGS) has been efficacious in helping the surgeon achieve negative
      margins. METHODS: The present study uses FGS in a mouse model that has undergone
      surgical orthotopic implantation (SOI) of colorectal liver metastasis tagged with
      green fluorescent protein (GFP). An anti-CEA antibody conjugated to DyLight 650
      was used to highlight the tumor. RESULTS: The fluorescent antibody clearly
      demarcated the lesion at deeper tissue depth compared to GFP. Fluorescence of the
      anti-CEA-DyLight650 showed maximal tumor-to-liver contrast at 72 hr. Fifteen mice
      underwent bright-light surgery (BLS) versus FGS with GFP versus FGS with anti-CEA
      DyLight650. Mice that underwent FGS had a significantly smaller area of residual
      tumor (P < 0.001) and significantly longer overall survival (P < 0.001) and
      disease-free survival (P < 0.001). Within the two FGS groups, mice undergoing
      surgery with anti-CEA-DyLight650 improved survival compared to only GFP labeling.
      CONCLUSIONS: In the present report, we demonstrate that an anti-CEA antibody
      conjugated to a DyLight 650 nm dye clearly labeled colon cancer liver metastases,
      thereby enabling successful FGS. J. Surg. Oncol. 2016;114:951-958. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27696452
TI  - European symposium on the awareness of allergy: report of the promotional
      campaign in the European Parliament (26-28 April 2016).
AB  - From 26 to 28 of April 2016, an allergy awareness campaign was organized by the
      European Academy of Allergy and Clinical Immunology and the European Federation
      of Allergy and Airway Diseases Patients Associations in the European Parliament
      in Brussels, with support of the European Parliament's Interest group on Allergy
      and Asthma and was co-hosted by the Members of the European Parliament David
      Borrelli, Sirpa Pietikainen and Nessa Childers. Skin prick tests (SPTs) were
      performed to gain attention for the increasing prevalence of allergic airway
      diseases in Europe. Since more than 30% of the total European population suffers
      from airway allergies and asthma, reaching a higher level of awareness and
      elaboration of an active prevention plan is mandatory. Of the 406 individuals
      undergoing SPT in the European Parliament, 211 participants (52%) reported to
      have suffered from an allergy in the past, with allergic symptoms being present
      in the nose and eyes (40% and 36%, respectively), the skin (27%), lower airways
      (14%) and the gut (8%). Of the 381 SPT with reliable results, cutaneous
      hypersensitivity was found in 201 (53%) participants. Of those with positive SPT
      (n = 201), 70 participants (35%) were monosensitized while 131 participants (65%)
      were polysensitized. The positive skin reactions were found mostly for grass
      pollen (n = 108), followed by Dermatophagoides pteronyssinus (n = 105),
      Dermatophagoides farina (n = 96) and birch pollen (n = 85). Of note, 54
      individuals (14% of the total tested population) without reported allergy or
      allergic symptoms showed a positive SPT without clinical relevance. This report
      summarizes the main idea and goals of the symposium: chronic airway diseases are
      a major and growing health problem in Europe. Therefore, a joint preventive
      action plan needs to be developed for a better health status of European
      citizens.

PMID- 27696453
TI  - Development and evaluation of a hydrophilic interaction liquid chromatography
      MS/MS method to quantify 19 nucleobases and nucleosides in rat plasma.
AB  - As essential endogenous compounds, nucleobases and nucleosides fulfill various
      functions in living organisms. This study presents the development and validation
      of a new hydrophilic interaction liquid chromatography tandem mass spectrometry
      method for simultaneous quantification of 19 nucleobases and nucleosides in rat
      plasma. For the sample preparation, 15 kinds of protein precipitants were
      evaluated according to the chromatographic profile and ion response of analytes.
      The optimization of chromatographic separation was respectively performed using
      reversed-phase liquid chromatography and hydrophilic interaction liquid
      chromatography mode; each separation mode included two test columns with
      different stationary phases. The chromatographic profile and parameters such as
      half-width (W1/2 ), capacity factor (K') and tailing factor (ft ) were used to
      evaluate the separation efficiencies. Furthermore, the adopted composition of two
      mobile phase systems and the concentrations of the additives in the optimum
      buffer system were also investigated. The developed method was fully validated
      and successfully applied quantitatively to determine 19 nucleobases and
      nucleosides in plasma from normal and diabetic nephropathy (DN) rats. Significant
      differences between normal and DN rats were found in plasma levels of cytosine,
      xanthine, thymidine, adenosine, guanosine, inosine and 8-hydroxy-2'
      deoxyguanosine. This information may provide a useful reference for the discovery
      of potential biomarkers of DN.

PMID- 27696454
TI  - Transfusion of 35-day stored red blood cells does not result in increase of
      plasma non-transferrin bound iron in human endotoxemia.
AB  - BACKGROUND: Transfusion of a single unit of stored red blood cells (RBCs) has
      been hypothesized to induce supra-physiological levels of non-transferrin bound
      iron (NTBI), which may enhance inflammation and act as a nutrient for bacteria.
      We investigated the relation between RBC storage time and iron levels in a
      clinically relevant "two-hit" human transfusion model. STUDY DESIGN AND METHODS:
      Eighteen healthy male volunteers (ages 18-35 years) were infused with 2 ng
      lipopolysaccharide (LPS)/kg to induce systemic inflammatory response syndrome.
      Two hours later, each participant received either 1 unit of 2-day stored (2D)
      autologous RBCs, 35-day stored (35D) autologous RBCs, or an equal volume of
      saline. Every 2 hours up to 8 hours after LPS infusion, hemoglobin, hemolysis
      parameters, and iron parameters, including NTBI, were measured. RESULTS:
      Transfusion of both 2D and 35D RBCs caused increases in hemoglobin, plasma iron,
      and transferrin saturation; whereas levels remained stable in the saline group.
      Transfusion of 35D RBCs did not result in hemolysis nor did it lead to increased
      levels of NTBI compared with 2D RBCs or saline. LPS induced increases in
      ferritin, haptoglobin, bilirubin, and lactate dehydrogenase that were similar in
      all three groups. CONCLUSION: We conclude that 35D autologous RBCs do not cause
      hemolysis or increased levels of NTBI during human endotoxemia.

PMID- 27696455
TI  - A new method for the assessment of the surface topography of NiTi rotary
      instruments.
AB  - AIM: To describe a new method for the assessment of nanoscale alterations in the
      surface topography of nickel-titanium endodontic instruments using a high
      resolution optical method and to verify the accuracy of the technique.
      METHODOLOGY: Noncontact three-dimensional optical profilometry was used to
      evaluate defects on a size 25, .08 taper reciprocating instrument (WaveOne(r) ),
      which was subjected to a cyclic fatigue test in a simulated root canal in a clear
      resin block. For the investigation, an original procedure was established for the
      analysis of similar areas located 3 mm from the tip of the instrument before and
      after canal preparation to enable the repeatability and reproducibility of the
      measurements with precision. All observations and analysis were taken in areas
      measuring 210 * 210 MUm provided by the software of the equipment. RESULTS: The
      three-dimensional high-resolution image analysis showed clear alterations in the
      surface topography of the examined cutting blade and flute of the instrument,
      before and after use, with the presence of surface irregularities such as
      deformations, debris, grooves, cracks, steps and microcavities. CONCLUSIONS:
      Optical profilometry provided accurate qualitative nanoscale evaluation of
      similar surfaces before and after the fatigue test. The stability and
      repeatability of the technique enables a more comprehensive understanding of the
      effects of wear on the surface of endodontic instruments.

PMID- 27696456
TI  - Systematic review with meta-analysis: endoscopic retrograde
      cholangiopancreatography-based modalities for the diagnosis of cholangiocarcinoma
      in primary sclerosing cholangitis.
AB  - BACKGROUND: The accuracy of current endoscopic modalities for diagnosing
      cholangiocarcinoma in primary sclerosing cholangitis (PSC) is suboptimal. AIM: To
      evaluate the comparative effectiveness of endoscopic retrograde
      cholangiopancreatography (ERCP)-based modalities, independently or in
      combination, for the diagnosis of cholangiocarcinoma in patients with PSC-induced
      biliary strictures. METHODS: Searches of PubMed, EMBASE, Web of Science and the
      Cochrane Library databases were performed through December 2015. Measured
      outcomes included sensitivity and specificity of all diagnostic modalities
      independently or in combination. A bivariate model was used to compute the pooled
      sensitivity and specificity, and to plot the summary receiver operating
      characteristics curve with summary point and corresponding 95% confidence
      interval (95% CI). A logistic regression model was used to impute the incremental
      performance of combining two diagnostic tests. RESULTS: Twenty-one studies met
      inclusion criteria: 13 on bile duct brushing for cytology, 7 on fluorescence in
      situ hybridisation (FISH), 2 on probe-based confocal laser endomicroscopy, and 4
      on single-operator cholangioscopy with targeted biopsies. Single-operator
      cholangioscopy with targeted biopsies was the most accurate diagnostic modality
      at 96% (95% CI, 94-97%). The pooled sensitivity and specificity of single
      operator cholangioscopy for diagnosis of cholangiocarcinoma in patients with PSC
      was 65% (95% CI, 35-87%) and 97% (95% CI, 87-99%), respectively. The pooled
      diagnostic odds ratio to detect cholangiocarcinoma was 59 (95% CI, 10-341).
      CONCLUSIONS: Single-operator cholangioscopy with targeted biopsies appears to be
      the most accurate ERCP-based modality for diagnosing cholangiocarcinoma in
      primary sclerosing cholangitis. However, future large, well-designed comparative
      diagnostic studies are warranted to validate these findings.

PMID- 27696458
TI  - Iron acquisition and siderophore production in the fish pathogen Renibacterium
      salmoninarum.
AB  - Renibacterium salmoninarum is the causative agent of bacterial kidney disease,
      which significantly affects salmonid farming worldwide. Despite this impact,
      there is scarce data on its iron uptake ability, a factor of pathogenesis. This
      study investigated the iron acquisition mechanisms of R. salmoninarum and its
      capacity to uptake iron from different sources. Thirty-two Chilean isolates and
      the DSM20767T type strain grew in the presence of 2,2'-Dipyridyl at varying
      concentrations (250-330 MUm), and all isolates positively reacted on chrome
      azurol S agar. Subsequently, inocula of four Chilean isolates and the type strain
      were prepared with or without 200 MUm of 2,2'-Dipyridyl for uptake assays. Assay
      results revealed differences between the isolates in terms of iron acquisition.
      While a prior iron-limited environment was, for most isolates, not required to
      activate the uptake of iron (II) sulphate, ammonium iron (III) citrate or iron
      (III) chloride at higher concentrations (100 MUm), it did facilitate growth at
      lower iron concentrations (10 MUm and 1 MUm). An exception was the H-2 isolate,
      which only grew with 100 MUm of iron sulphide. In turn, 100 MUm of haemin was
      toxic when isolates were grown in normal KDM-2. In silico R. salmoninarumATCC
      33209T genome analysis detected various genes coding iron uptake-related
      proteins. This is the first study indicating two iron acquisition systems in R.
      salmoninarum: one involving siderophores and another involving haem group
      utilization. These data represent a first step towards fully elucidating this
      virulence factor in the pathogenic R. salmoninarum.

PMID- 27696457
TI  - Glyoxalase 2 Is Involved in Human Prostate Cancer Progression as Part of a
      Mechanism Driven By PTEN/PI3K/AKT/mTOR Signaling With Involvement of PKM2 and
      ERalpha.
AB  - BACKGROUND: Glyoxalase 2 (Glo2), together with glyoxalase 1 (Glo1), forms the
      main scavenging system of methylglyoxal, a potent pro-apoptotic agent mainly
      generated by glycolysis. An increased rate of glycolysis is a well known
      signature of cancer cells. As a survival strategy, Glo1 is overexpressed in many
      human malignant cells, including prostate cancer (PCa), where it plays a crucial
      role in progression. No information is available on the role of Glo2 in the same
      ambit. PCa is the most common malignancy affecting men in the western world.
      Progression to a lethal hormone-refractory PCa represents the major concern in
      this pathology. Therefore, a deeper understanding of the molecular mechanisms
      underlying PCa invasiveness and metastasis is urgently needed in order to develop
      novel therapeutic targets for this incurable state of the malignancy. METHODS:
      Glo2 and Glo1 expression was examined in clinical samples of PCa by
      immunohistochemistry and in different PCa cell models by western blotting and
      quantitative real-time polymerase chain reaction. Gene silencing/overexpression
      and scavenging/inhibitory agents were used for functional analyses. RESULTS: We
      demonstrated that Glo2, together with Glo1, represents a novel mechanism in PCa
      progression as part of a pathway driven by PTEN/PI3K/AKT/mTOR signaling with
      involvement of PKM2 and ERalpha. Importantly, Glo1/Glo2 silencing did not alter
      the behavior of benign cells. CONCLUSIONS: Targeting glyoxalases metabolic
      pathway may represent a strategy to selectively inhibit advanced PCa. Prostate
      77:196-210, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696459
TI  - QTAIM and stress tensor interpretation of the (H2 O)5 potential energy surface.
AB  - Using the quantum theory of atoms in molecules a near complete combined directed
      spanning quantum topology phase diagram (QTPD) was constructed from the nine (H2
      O)5 reaction-pathways and five unique Poincare-Hopf solutions that were found
      after an extensive search of the MP2 potential energy surface. Two new energy
      minima that were predicted from earlier work are found and include the first (H2
      O)5 conformer with a 3-DQT quantum topology. The stress tensor Poincare-Hopf
      relation indicated a preference for 2-DQT (H2 O)5 topologies as well as the
      presence of coupling between shared-shell O?H BCPs to the hydrogen-bond BCPs that
      share an H NCP. The complexity of the near complete combined QTPD was explained
      in terms of the O...O bonding interactions that were found in six of the nine (H2
      O)5 reaction-pathways and for all points of the combined QTPD. The stabilizing
      role of the O...O bonding interactions from the values of the total local energy
      density was explored. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696460
TI  - Genetic variability of respiratory syncytial virus A in hospitalized children in
      the last five consecutive winter seasons in Central Spain.
AB  - Human respiratory syncytial virus group A (RSV-A) was detected in symptomatic
      hospital attended children in Central Spain for a continuous time period,
      September 2010 to April 2015. In order to accurately describe the epidemiology of
      this virus, the genetic diversity of the complete G gene and the clinical
      manifestations observed were jointly analyzed. Out of 3,011 respiratory specimens
      taken from 2,308 children, 640 were positive to RSV (21.3%) and 405 were RSV-A
      (63.2%). Complete G gene sequences of 166 randomly selected RSV-A virus
      identified NA1 and ON1 genotypes. In 2011-2012, ON1 emerged sporadically and
      become dominant in 2012-2013 with 38 cases (70%). In 2014-2015, all the 44
      sequences contained the 72-nt duplication (100%). Clinical diagnosis of children
      with ON1 genotype were bronchiolitis in 55 (62.5%), recurrent wheezing or asthma
      exacerbations in 22 (25%), laryngotracheobronchitis in 3 (3.4%), and upper
      respiratory tract infections in eight. Results showed replacement and
      substitution of circulating NA1 genotype with the new ON1 genotype. Nevertheless,
      at this stage, none of the RSV-A genotypes identified have resulted in
      significant clinical differences. The amino acid composition of the complete G
      gene ON1 sequences demonstrated an accumulation of single changes not related
      with different clinical presentation. J. Med. Virol. 89:767-774, 2017. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27696461
TI  - Methods and Variables Associated with the Risk of Septic Arthritis Following
      Intra-Articular Injections in Horses: A Survey of Veterinarians.
AB  - OBJECTIVE: To determine common methods for intra-articular injections and
      variables associated with the risk of septic arthritis following intra-articular
      injection in the horse. STUDY DESIGN: Cross-sectional survey. SAMPLE POPULATION:
      Equine veterinarians. METHODS: A link to an online survey was distributed to
      equine practitioners in 2014. Responses for descriptive data were tabulated. Data
      on infection rates obtained from medical records were analyzed. Variables
      associated with the risk of septic arthritis were determined using chi2 or
      Fisher's exact tests and logistic regression. RESULTS: Common current methods for
      intra-articular injections were determined from 241 surveys. Sixty-four of 241
      surveys (26.6%) contained data with numbers of joints injected and number of
      infections obtained from review of medical records. Eight different injection
      methods were used by more than 2/3 of responding veterinarians. A total of 67 out
      of 319,760 injected joints reported became septic following injection, giving an
      incidence of 2.10 septic joints per 10,000 intra-articular injections. Based on
      multivariate analysis, infection rates were significantly lower when
      veterinarians prepared their own injection sites (OR=0.10) and had <20 years of
      practice experience (OR=0.025), whereas infection rates were significantly higher
      when hair was removed at the injection site (OR=19.70). CONCLUSION: There is a
      low incidence of septic arthritis following intra-articular injection and a large
      number of injection methods reported by responding veterinarians. The low
      reported incidence of infection may be related to the large number of
      practitioners frequently using common methods.

PMID- 27696462
TI  - An early innate response underlies severe influenza-induced exacerbations of
      asthma in a novel steroid-insensitive and anti-IL-5-responsive mouse model.
AB  - BACKGROUND: Acute worsening of asthma symptoms (exacerbation) is predominantly
      triggered by respiratory viruses, with influenza causing the most severe
      exacerbations. The lack of an adequate animal model hampers mechanistic insight
      and the development of new therapeutics. AIM: We developed and characterized a
      robust, consistent, and reproducible mouse model of severe exacerbation of
      chronic allergic asthma. METHODS: Chronic allergic airway inflammation was
      induced following a house dust mite (HDM) sensitization protocol. HDM-sensitized
      mice and controls were infected with influenza virus A/X31 H3N2 and either or not
      treated with inhaled fluticasone propionate (FP), systemic corticosteroids
      (Pred), or anti-IL-5. Mice were killed at different time points after infection:
      Cellular accumulation and cytokines levels in the airways, PenH as a measure of
      airway hyper-responsiveness (AHR), and lung histology and viral replication were
      assessed. RESULTS: Infection with low-dose A/X31 H3N2 led to prolonged
      deterioration of lung function, aggravated mucus production, peri-vascular, peri
      bronchial, and allergic inflammation that was unresponsive to inhaled
      corticosteroids, but responsive to systemic corticosteroids. The exacerbation was
      preceded at 14 h after virus exposure by a marked innate, but no Th2 and Th1
      response subsequently followed by enhanced numbers of eosinophils, neutrophils,
      dendritic, and T cells into the lung lumen, parenchyma, and draining lymph nodes
      in HDM-sensitized mice. Anti-IL-5 treatment attenuated eosinophils and prevented
      the X31-induced exacerbation. CONCLUSIONS: Together, these findings indicate that
      an early innate response that involves eosinophils underlies the exacerbation.
      This model recapitulates all major features of severe asthma exacerbations and
      can serve to discern driving mechanisms and promote the development of novel
      therapeutics.

PMID- 27696463
TI  - Design and validation of an STR hexaplex assay for DNA profiling of grapevine
      cultivars.
AB  - Although the analysis of length polymorphism at STR loci has become a method of
      choice for grape cultivar identification, the standardization of methods for this
      purpose lags behind that of methods for DNA profiling in human and animal
      forensic genetics. The aim of this study was thus to design and validate a
      grapevine STR protocol with a practically useful level of multiplexing. Using
      free bioinformatics tools, published primer sequences, and nucleotide databases,
      we constructed and optimized a primer set for the simultaneous analysis of six
      STR loci (VVIi51, scu08vv, scu05vv, VVMD17, VrZAG47, and VrZAG83) by multiplex
      PCR and CE with laser-induced fluorescence, and tested it on 90 grape cultivars.
      The new protocol requires subnanogram quantities of the DNA template and enables
      automated, high-throughput genetic analysis with reasonable discriminatory power.
      As such, it represents a step toward further standardization of grape DNA
      profiling.

PMID- 27696464
TI  - Hazards in chromatographic bioanalysis method development and applications.
AB  - Bioanalytical methods are employed for the quantitative determination of drugs
      and their metabolites in biological matrices, in all stages of the drug
      development process. However, because of the highly complex nature of these
      matrices there is a wide range of potential biological, chemical and physical
      hazards that can influence the quality of the data produced by these methods. The
      present review focuses on the evaluation of the most important and frequent
      errors that may be encountered during bioanalytical method development/validation
      and analysis of clinical or preclinical samples mainly using chromatography.
      Additionally, the most practical ways for avoiding and managing these hazards
      during routine bioanalysis are presented.

PMID- 27696466
TI  - Virucide properties of cold atmospheric plasma for future clinical applications.
AB  - Cold atmospheric plasma (CAP) has been repeatedly identified to bear powerful
      microbicidal efficacy on bacteria including multidrug resistant organisms and
      fungi on non-living surfaces, in biofilms as well as on contaminated and infected
      tissues. CAP furthermore was found to stimulate wound healing in chronic wounds
      and exerted anti-neoplastic effects on numerous tumor entities. Thus, CAP
      represents a promising medical tool for many clinical and therapeutic issues.
      Studies about CAP effects on virus particles recently were in arrears, but to
      date increasingly move into the focus of interest. Apparently, CAP treatment is
      followed by a promising virus inactivation and contributes to tissue
      regeneration. Here we review the current state of science concerning the so far
      investigated CAP effects on different virus species and virus-associated
      disorders. J. Med. Virol. 89:952-959, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 27696465
TI  - Characteristics of carcinogenic human papillomavirus infection in Suzhou:
      Epidemiology, vaccine evaluation, and associated diseases.
AB  - Human papillomavirus infection is a major health problem and caused substantial
      benign and malignancy diseases among female and male worldwide. We aim to
      investigate the epidemiology of high-risk human papillomavirus (HR-HPV) and
      related diseases in Suzhou population. As well as evaluating the potential
      benefit of a nine-valent HPV vaccine (regardless of HPV-6 and -11) in Suzhou. A
      total of 40,108 people aged 13-89 years were retrospectively examined by database
      retrieval from 2010 to 2015. Thirteen genotypes (16, 18, 31, 33, 35, 39, 45, 51,
      52, 56, 58, 59, and 66) of HR-HPV were detected using TellgenplexTM xMAPTM HPV
      DNA Test assay. The overall prevalence of HR-HPV was 21.1%, the female and male
      account for 96.4% and 3.6%, respectively. The infection rate among male (25.6%,
      367/1,432) was significantly higher than that among female (20.9%, 8,100/38,676),
      X2  = 17.341 (P < 0.001), with OR = 1.293, 95% CI (1.146-1.460). The five most
      frequent HR-HPV genotypes were HPV-16 (5.12%), -52 (5.07%), -58 (3.02%), -39
      (2.00%), and -18 (1.74%). HR-HPV infection rate was peak in person aged <20
      years, and second higher in person aged 51-60 years. Infection modes as HPV-16, 
      18, -31, -33, -45, -52, -58 alone or mixed accounted for 63.2%. The top three
      prevalent diseases in HR-HPV infected women were cervicitis, vaginitis, and
      cervical lesions, and in men were verruca, urethritis, and balanitis,
      respectively. This is the first study to demonstrate HPV infection status in
      Suzhou population. Both women and men had a large burden of HPV infection. The
      nine-valent HPV prophylactic vaccines may potentially prevent 63.2% HR-HPV
      infection in Suzhou. J. Med. Virol. 89:895-901, 2017. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27696467
TI  - Determination of ethyl glucuronide and fatty acid ethyl esters in hair samples.
AB  - Hair testing for alcohol biomarkers is an important tool for monitoring alcohol
      consumption. We propose two methods for assessing alcohol exposure through
      combined analysis of ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs)
      species (ethyl myristate, palmitate, stearate and oleate) in hair (30 mg). EtG
      was analysed by liquid chromatography-tandem mass spectrometry, while FAEEs were
      analysed by gas chromatography-tandem mass spectrometry using electron impact
      ionization. Both methods were validated according to internationally accepted
      guidelines. Linearity was proven between 3 and 500 pg/mg for EtG and 30-5000
      pg/mg for FAEEs, and the limits of quantification were 3 pg/mg for EtG and 30
      pg/mg for each of the four FAEEs. Precision and accuracy were considered
      adequate, processed EtG samples were found to be stable for up to 96 h left in
      the injector and processed FAEEs samples for up to 24 h. Matrix effects were not
      significant. Both methods were applied to the analysis of 15 authentic samples,
      using the cut-off values proposed by the Society of Hair Testing for
      interpretation. The results agreed well with the self-reported alcohol
      consumption in most cases, and demonstrated the suitability of the methods to be
      applied in routine analysis of alcohol biomarkers, allowing monitoring
      consumption using low sample amounts.

PMID- 27696468
TI  - Validity of Exercise Measures in Adults with Anorexia Nervosa: The EDE,
      Compulsive Exercise Test and Other Self-Report Scales.
AB  - OBJECTIVE: Compulsive exercise is a prominent feature for the majority of
      patients with Anorexia Nervosa (AN), but there is a dearth of research evaluating
      assessment instruments. This study assessed the concurrent validity of the
      exercise items of the Eating Disorder Examination (EDE) and Eating Disorder
      Examination-Questionnaire (EDE-Q), with the Compulsive Exercise Test (CET) and
      other self-report exercise measures in patients with AN. We also aimed to perform
      validation of the CET in an adult clinical sample. METHODS: The sample consisted
      of 78 adults with AN, recruited for the randomized controlled trial "Taking a
      LEAP forward in the treatment of anorexia nervosa." At baseline, participants
      completed the EDE, EDE-Q, CET, Reasons for Exercise Inventory (REI), Commitment
      to Exercise Scale (CES) and Exercise Beliefs Questionnaire (EBQ). Correlational
      and regression analyses were performed. RESULTS: EDE exercise days and exercise
      time per day were positively correlated with each other and with all CET
      subscales (except Lack of exercise enjoyment), CES mean, EBQ total and REI total.
      Exercise time per day was associated with a higher EDE global score. The CET
      demonstrated good concurrent validity with the CES, the REI and the EBQ. Of the
      self-reports, the CET explained the greatest variance in eating disorder
      psychopathology and demonstrated good to excellent reliability in this sample.
      DISCUSSION: The EDE and EDE-Q demonstrated good concurrent validity with the CET.
      Further research is required to evaluate the CET's factor structure in a large
      clinical sample. However, the CET has demonstrated strong clinical utility in
      adult patients with AN. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017;
      50:533-541).

PMID- 27696469
TI  - Three dimensional ultrasonography for advanced neurosonography (Neurosofe-3d).
      Analysis of acquisition-related factors influencing the quality of the brain
      volumes.
AB  - OBJECTIVE: To evaluate the acquisition-related factors influencing the quality of
      the brain volumes for further study of advanced neurosonography. METHODS: This
      was a prospective multicentre study. Five centres were asked to include five
      cases each, acquiring two volumes per case, at different gestational ages. Ten
      operators performed an advanced neurosonography per case. The potential influence
      of the following factors on the number of evaluable structures was assessed:
      vaginal/ abdominal acquisition, position of the head, gestational age, subjective
      quality of the volume and the acquiring operator itself. RESULTS: Four hundred
      and thirty-two evaluations were included in the study. A total of 80% of the
      structures were evaluated satisfactorily in the axial plane, 67.1% and 55.1% in
      the coronal and sagittal plane, respectively. Sagittal volumes acquired
      transvaginally had a better quality than those acquired transabdominally.
      Gestational age affected the quality of axial and sagittal volumes (p < 0.001),
      and the best quality was obtained between 20 and 27 weeks. In axial and sagittal
      volumes, the head position influenced the percentage of structures visualized (p
      < 0.001, p < 0.001). CONCLUSIONS: Factors affecting the quality of the volume for
      advanced neurosonography are gestational age, fetal head position, transvaginal
      acquisition in sagittal volumes, the acquiring operator and the subjective
      quality of the volume. (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696471
TI  - Global proteomic analysis of lysine acetylation in zebrafish (Danio rerio)
      embryos.
AB  - Lysine acetylation is an important post-translational modification (PTM). Since
      the development of MS-based proteomics technology, important roles of lysine
      acetylation beyond histones have focused on chromatin remodeling during the cell
      cycle and regulation of nuclear transport, metabolism, and translation. Zebrafish
      (Danio rerio) is a widely used vertebrate model in genetics and biologic studies.
      Although studies in several mammalian species have been performed, the mechanism
      of lysine acetylation in D. rerio embryos is incompletely understood. Here, we
      investigated the global acetylome in D. rerio embryos by using an MS-based
      proteomics approach. We identified 351 acetylated peptides and 377 nonredundant
      acetylation sites on 189 lysine-acetylated proteins in 5-day postfertilization
      (hpf) embryos of D. rerio. Among lysine-acetylated peptides, 40.2% indicated
      three motifs: (ac)KxxxK, (ac)KxxxxK, and Lx(ac)K. Of 190 acetylated proteins, 81
      (42.6%) were mainly distributed in the cytoplasm. Gene ontology enrichment and
      Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that lysine
      acetylation in D. rerio was enriched in metabolic pathways. Additionally, 17 of
      30 acetylated ribosomal proteins were evolutionarily conserved between zebrafish
      and humans. Our results indicate that acetyllysine might have regulatory effects
      on ribosomal proteins involved in protein biosynthesis.

PMID- 27696470
TI  - Disposition of intravenously or orally administered silver nanoparticles in
      pregnant rats and the effect on the biochemical profile in urine.
AB  - Few investigations have been conducted on the disposition and fate of silver
      nanoparticles (AgNP) in pregnancy. The distribution of a single dose of
      polyvinylpyrrolidone (PVP)-stabilized AgNP was investigated in pregnant rats. Two
      sizes of AgNP, 20 and 110 nm, and silver acetate (AgAc) were used to investigate
      the role of AgNP diameter and particle dissolution in tissue distribution,
      internal dose and persistence. Dams were administered AgNP or AgAc intravenously
      (i.v.) (1 mg kg-1 ) or by gavage (p.o.) (10 mg kg-1 ), or vehicle alone, on
      gestation day 18 and euthanized at 24 or 48 h post-exposure. The silver
      concentration in tissues was measured using inductively-coupled plasma mass
      spectrometry. The distribution of silver in dams was influenced by route of
      administration and AgNP size. The highest concentration of silver (MUg Ag g-1
      tissue) at 48 h was found in the spleen for i.v. administered AgNP, and in the
      lungs for AgAc. At 48 h after p.o. administration of AgNP, the highest
      concentration was measured in the cecum and large intestine, and for AgAc in the
      placenta. Silver was detected in placenta and fetuses for all groups. Markers of
      cardiovascular injury, oxidative stress marker, cytokines and chemokines were not
      significantly elevated in exposed dams compared to vehicle-dosed control. NMR
      metabolomics analysis of urine indicated that AgNP and AgAc exposure impact the
      carbohydrate, and amino acid metabolism. This study demonstrates that silver
      crosses the placenta and is transferred to the fetus regardless of the form of
      silver. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696472
TI  - Comparative analysis of prostate-specific antigen by two-dimensional gel
      electrophoresis and capillary electrophoresis.
AB  - Serum levels of Prostate-Specific Antigen (PSA) are not fully specific for
      prostate cancer (PCa) diagnosis and several efforts are focused on searching to
      improve PCa markers through the study of PSA subforms that could be cancer
      associated. We have previously reported by 2DE a decrease in the sialic acid
      content of PSA from PCa compared to benign prostatic hyperplasia patients based
      on the different proportion of the PSA spots. However, faster and more
      quantitative techniques, easier to automate than 2DE, are desirable. In this
      study, we examined the potential of CE for resolving PSA subforms in different
      samples and compared the results with those obtained by 2DE. We first
      fractionated by OFFGEL the subforms of PSA from seminal plasma according to their
      pIs and analyzed each separated fraction by 2DE and CE. We also analyzed PSA and
      high pI PSA, both from seminal plasma, and PSA from urine of a PCa patient. These
      samples with different PSA spots proportions by 2DE, due to different
      posttranslational modifications, also presented different CE profiles. This study
      shows that CE is a useful and complementary technique to 2DE for analyzing
      samples with different PSA subforms, which is of high clinical interest.

PMID- 27696473
TI  - Transfusion-related immunomodulation: review of the literature and implications
      for pediatric critical illness.
AB  - Transfusion-related immunomodulation (TRIM) in the intensive care unit (ICU) is
      difficult to define and likely represents a complicated set of physiologic
      responses to transfusion, including both proinflammatory and immunosuppressive
      effects. Similarly, the immunologic response to critical illness in both adults
      and children is highly complex and is characterized by both acute inflammation
      and acquired immune suppression. How transfusion may contribute to or perpetuate
      these phenotypes in the ICU is poorly understood, despite the fact that
      transfusion is common in critically ill patients. Both hyperinflammation and
      severe immune suppression are associated with poor outcomes from critical
      illness, underscoring the need to understand potential immunologic consequences
      of blood product transfusion. In this review we outline the dynamic immunologic
      response to critical illness, provide clinical evidence in support of
      immunomodulatory effects of blood product transfusion, review preclinical and
      translational studies to date of TRIM, and provide insight into future research
      directions.

PMID- 27696474
TI  - Melatonin exacerbates acute experimental autoimmune encephalomyelitis by
      enhancing the serum levels of lactate: A potential biomarker of multiple
      sclerosis progression.
AB  - Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS).
      In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5
      6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis
      (EAE) followed by assessing serum levels of lactate and melatonin. Results showed
      that clinical outcomes were exacerbated in melatonin- (neurological score = 6) vs
      PBS-treated EAE rats (score = 5). Melatonin caused a significant increase in
      serum IFN-gamma, in comparison to PBS-treated EAE rats whereas no considerable
      change in IL-4 levels were found, although they were significantly lower than
      those of controls. The ratio of IFN-gamma/IL-4, an indicator of Th-1/Th-2, was
      significantly higher in PBS- and melatonin- treated EAE rats, in comparison to
      controls. Moreover, results showed increased lymphocyte infiltration, activated
      astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP-deficient
      areas) in the lumbar spinal cord of melatonin-treated EAE rats. Finally, serum
      levels of lactate, but not melatonin, significantly increased in the melatonin
      group, compared to untreated EAE and normal rats. In conclusion, our results
      indicated a relationship between age and the development of EAE since a negative
      impact was found for melatonin on EAE recovery of young rats by enhancing IFN
      gamma, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay
      the remyelination process. While melatonin levels decline in MS patients, lactate
      might be a potential diagnostic biomarker for prediction of disease progression.
      Early administration of melatonin in the acute phase of MS might be harmful and
      needs further investigations.

PMID- 27696475
TI  - A randomized and double-blind controlled trial evaluating the safety and efficacy
      of rituximab for warm auto-immune hemolytic anemia in adults (the RAIHA study).
AB  - This Phase 3 multicentre randomized double-blind and placebo-controlled trial
      aimed to compare the efficacy and safety of rituximab (RTX) to placebo for
      treating newly diagnosed warm autoimmune hemolytic anemia (wAIHA) in adults
      receiving prednisone. Adults with a confirmed diagnosis of wAIHA who previously
      received corticosteroids for less than 6 weeks could be included. At inclusion,
      all patients received prednisone at a daily dose of 1 mg/kg for 2 weeks, and then
      tapered according to a pre-defined recommended reduction scheme. Besides
      prednisone, eligible patients received 2 infusions of RTX or placebo at a fixed
      dose of 1,000 mg 2-week apart. The primary endpoint was overall response rate
      (complete response [CR] + partial response [PR]) in an intent-to-treat (ITT)
      analysis at 1 year. A total of 32 patients (17 females [53%], mean age at
      inclusion 71 +/- 16 years) were enrolled and randomized. In all, 27 patients were
      followed for at least 1 year and their data were evaluable for response. With an
      ITT analysis, the overall response rate at 1 year was 75% [95%CI: 47.6-92.7] with
      11 CR and 1 PR with RTX versus 31% [11.0-58.7] (5 CR) with placebo (P = 0.032).
      At 2 years, 10/16 patients with RTX versus 3/16 with placebo still showed CR (P =
      0.011). Overall, eight severe infections occurred during follow-up, six with
      placebo and two with RTX (P = 0.39). At 2 years, six patients with placebo had
      died, but none with RTX (P = 0.017). Compared to placebo, RTX combined with
      prednisone may be effective and safe for treating newly-diagnosed wAIHA in
      adults. Am. J. Hematol. 92:23-27, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696477
TI  - The 67th Annual Meeting of the American Association for the Study of Liver
      Diseases: The Liver Meeting 2016.

PMID- 27696476
TI  - Radiosynthesis of novel pitavastatin derivative ([18 F]PTV-F1) as a tracer for
      hepatic OATP using a one-pot synthetic procedure.
AB  - Pitavastatin is an antihyperlipidemic agent, a potent inhibitor of 3
      hydroxymethyl-glutaryl-CoA reductase, which is selectively taken up into the
      liver mainly via hepatic organic anion transporting polypeptide 1B1 (OATP1B1).
      OATP1B1 can accept a variety of organic anions, and previous reports indicated
      that it is responsible for the hepatic clearance of several clinically used
      anionic drugs. Therefore, the pharmacokinetics and the hepatic distribution of
      pitavastatin provide an insight into the function of OATP1B1 in humans. For the
      development of the in vivo evaluation of OATP1B1 function by positron emission
      tomography imaging, we designed a novel [18 F]pitavastatin derivative ([18 F]PTV
      F1), in which a [18 F]fluoroethoxy group is substituted for the [18 F]fluoro
      group of [18 F]pitavastatin, with the aim of convenient radiolabeling protocol
      and high radiochemical yield. In vitro studies suggested that transport
      activities of PTV-F1 mediated by OATP1B1 and OATP1B3 were very similar to those
      of pitavastatin and PTV-F1 was metabolically stable in human liver microsomes. In
      the radiosynthesis of [18 F]PTV-F1 from the tosylate precursor, nucleophilic
      fluorination and subsequent deprotection were performed using a one-pot
      procedure. [18 F]PTV-F1 was obtained with a radiochemical yield of 45% +/- 3% (n
      = 3), and the operating time for the radiosynthesis of [18 F]PTV-F1 is very short
      (30 minutes) compared with [18 F]pitavastatin.

PMID- 27696478
TI  - Letter: is HIV infection an important factor for liver fibrosis?

PMID- 27696479
TI  - Letter: gastritis in paediatric patients with coeliac disease - authors' reply.

PMID- 27696480
TI  - Letter: is HIV infection an important factor for liver fibrosis? Authors' reply.

PMID- 27696481
TI  - Letter: gastritis in paediatric patients with coeliac disease.

PMID- 27696482
TI  - Prostate Cancer Cells in Different Androgen Receptor Status Employ Different
      Leucine Transporters.
AB  - BACKGROUND: Leucine stimulates cancer cell proliferation through the mTOR
      pathway, therefore, inhibiting leucine transporters may be a novel therapeutic
      target for cancer. L-type amino acid transporter (LAT) 1, a Na+ -independent
      amino acid transporter, is highly expressed in many tumor cells. However, leucine
      transporter(s) in different stages of prostate cancer, particularly in the stages
      of castration resistance with androgen receptor (AR) expression, is unclear.
      METHODS: LNCaP and DU145 and PC-3 cell lines were used as a model of androgen
      dependent, and metastatic prostate cancer. A new "LN-cr" cell line was
      established after culturing LNCaP cells for 6 months under androgen-free
      conditions, which is considered a model of castration resistant prostate cancer
      (CRPC) with androgen AR expression. The expression of leucine transporters was
      investigated with quantitative PCR and immunofluorescence. Uptake of 14 C Leucine
      was examined in the presence or absence of BCH (a pan-LAT inhibitor), JPH203 (an
      LAT1-specific inhibitor), or Na+ . Cell growth was assessed with MTT assay. siRNA
      studies were performed to evaluate the indispensability of y+ LAT2 on leucine
      uptake and cell viability in LN-cr. RESULTS: Cell viability showed a 90% decrease
      in the absence of leucine in all four cell lines. LNCaP cells principally
      expressed LAT3, and their leucine uptake was more than 90% Na+ -independent. BCH,
      but not JPH203, inhibited leucine uptake, and cell proliferation (IC50BCH :15
      mM). DU145 and PC-3 cells predominantly expressed LAT1. Leucine uptake and cell
      growth were suppressed by BCH or JPH203 in a dose-dependent manner (IC50BCH : ~20
      mM, IC50JPH203 : ~5 uM). In LN-cr cells, Na+ -dependent uptake of leucine was 3.8
      pmol/mgprotein/min, while, Na+ -independent uptake was only 0.52 (P < 0.05).
      Leucine uptake of LN-cr was largely (~85%) Na+ -dependent. y+ LAT2 expression was
      confirmed in LN-cr. Knockdown of y+ LAT2 lead to significant leucine uptake
      inhibition (40%) and cell growth inhibition (20%). CONCLUSIONS: New CRPC cell
      line with increased expression of y+ LAT2 as a leucine transporter was
      established in vitro. Anti-leucine transporter therapy could be an important
      option against prostate cancer. Prostate 77:222-233, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27696484
TI  - Newborns still lack drug data to guide therapy.

PMID- 27696485
TI  - Measles virus genotypes circulating in India, 2011-2015.
AB  - The Government of India is accepted to participate in the measles elimination and
      rubella control goal 2020, hence genetic characterization of measles viruses
      (MeV) becomes essential. At National Reference Laboratory (National Institute of
      Virology, Pune), the throat swabs/urine specimens (n = 380) or PCR products (n =
      219) obtained from the suspected measles cases were referred for the molecular
      testing and subsequently, MeV nucleoprotein (N) gene sequencing/genotyping. In
      addition, 2,449 suspected measles cases, mainly from the Maharashtra state were
      referred for the laboratory diagnosis. A detailed study was performed on N gene
      sequences obtained during last two decades. Indian MeV sequences obtained during
      2011-2015 were compared with 1996-2010 sequences and genetic divergence was
      studied. Circulation of measles genotypes B3 (n = 3), D4 (n = 49), and D8 (n =
      351) strains were observed in 19 States and three Union Territories of India. In
      addition, 64 measles viruses were isolated from 253 throat swab or urine
      specimens obtained from the suspected measles cases. During 2011-2015, 67.9%
      (1,663/2,449) suspected measles cases were laboratory confirmed. Molecular
      studies showed circulation of measles genotype B3 in India along with prominently
      circulating genotypes D4 and D8 except D7 strains. The genetic diversion within
      Indian B3, D4, and D8 genotypes was 0.3%, 1.1%, and 2.1%, respectively. The
      genetic divergence of Indian B3, D4, and D8 measles strains with the WHO
      reference sequences was 2.5%, 2.6%, and 1.8%, respectively. It is crucial data
      for national immunization program. More measles/rubella genotyping studies are
      necessary to track transmission and to support measles elimination and rubella
      control. J. Med. Virol. 89:753-758, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696483
TI  - Incidence and impact of subclinical epileptiform activity in Alzheimer's disease.
AB  - OBJECTIVE: Seizures are more frequent in patients with Alzheimer's disease (AD)
      and can hasten cognitive decline. However, the incidence of subclinical
      epileptiform activity in AD and its consequences are unknown. Motivated by
      results from animal studies, we hypothesized higher than expected rates of
      subclinical epileptiform activity in AD with deleterious effects on cognition.
      METHODS: We prospectively enrolled 33 patients (mean age, 62 years) who met
      criteria for AD, but had no history of seizures, and 19 age-matched, cognitively
      normal controls. Subclinical epileptiform activity was assessed, blinded to
      diagnosis, by overnight long-term video-electroencephalography (EEG) and a 1-hour
      resting magnetoencephalography exam with simultaneous EEG. Patients also had
      comprehensive clinical and cognitive evaluations, assessed longitudinally over an
      average period of 3.3 years. RESULTS: Subclinical epileptiform activity was
      detected in 42.4% of AD patients and 10.5% of controls (p = 0.02). At the time of
      monitoring, AD patients with epileptiform activity did not differ clinically from
      those without such activity. However, patients with subclinical epileptiform
      activity showed faster declines in global cognition, determined by the Mini
      Mental State Examination (3.9 points/year in patients with epileptiform activity
      vs 1.6 points/year in patients without; p = 0.006), and in executive function (p
      = 0.01). INTERPRETATION: Extended monitoring detects subclinical epileptiform
      activity in a substantial proportion of patients with AD. Patients with this
      indicator of network hyperexcitability are at risk for accelerated cognitive
      decline and might benefit from antiepileptic therapies. These data call for more
      sensitive and comprehensive neurophysiological assessments in AD patient
      evaluations and impending clinical trials. Ann Neurol 2016;80:858-870.

PMID- 27696487
TI  - Core skeletal muscle ryanodine receptor calcium release complex.
AB  - The core skeletal muscle ryanodine receptor (RyR1) calcium release complex
      extends through three compartments of the muscle fibre, linking the extracellular
      environment through the cytoplasmic junctional gap to the lumen of the internal
      sarcoplasmic reticulum (SR) calcium store. The protein complex is essential for
      skeletal excitation-contraction (EC)-coupling and skeletal muscle function. Its
      importance is highlighted by perinatal death if any one of the EC-coupling
      components are missing and by myopathies associated with mutation of any of the
      proteins. The proteins essential for EC-coupling include the DHPR alpha1S subunit
      in the transverse tubule membrane, the DHPR beta1a subunit in the cytosol and the
      RyR1 ion channel in the SR membrane. The other core proteins are triadin and
      junctin and calsequestrin, associated mainly with SR. These SR proteins are not
      essential for survival but exert structural and functional influences that modify
      the gain of EC-coupling and maintain normal muscle function. This review
      summarises our current knowledge of the individual protein/protein interactions
      within the core complex and their overall contribution to EC-coupling. We
      highlight significant areas that provide a continuing challenge for the field.
      Additional important components of the Ca2+ release complex, such as FKBP12,
      calmodulin, S100A1 and Stac3 are identified and reviewed elsewhere.

PMID- 27696488
TI  - Primary cutaneous adenosquamous carcinoma of the penis: the first
      characterization of HPV status in this rare and diagnostically challenging entity
      with review of glandular carcinomas of the penis.
AB  - Glandular and pseudoglandular tumors of the penile skin are extremely uncommon
      and can present diagnostic challenges. Primary adenosquamous carcinoma of the
      penis is an extremely rare tumor, composed of distinct areas of malignant
      squamous and glandular cells, making it a diagnostically challenging entity. The
      World Health Organization (WHO) recognizes several subtypes of squamous cell
      carcinoma (SCC), each with its own distinctive pathologic appearance, clinical
      associations and prognosis. Among these variants is the exceedingly uncommon
      adenosquamous carcinoma (ASC), representing 1%-2% of all SCC of the penis. Recent
      large studies have interrogated the presence of human papillomavirus (HPV) in
      malignant penile tumors and have shown specific morphologic patterns and clinical
      presentations to associate with HPV status. However, given the rarity of the
      adenosquamous variant of SCC, it has largely been excluded from these studies.
      The glandular components of these lesions can present a confusing appearance,
      particularly when a large tumor is represented on a small biopsy. Here we
      describe a difficult histologic presentation of this rare tumor, with the first
      published characterization of the HPV status of this subtype. This case
      represents a distinctly unusual case of metastatic HPV-positive primary cutaneous
      adenosquamous carcinoma of the penis.

PMID- 27696486
TI  - Nucleotide Excision Repair: Finely Tuned Molecular Orchestra of Early Pre
      incision Events.
AB  - Nucleotide excision repair (NER) eliminates a broad variety of helix-distorting
      DNA lesions that can otherwise cause genomic instability. NER comprises two
      distinct subpathways: global genomic NER (GG-NER) operating throughout the
      genome, and transcription-coupled NER (TC-NER) preferentially removing DNA
      lesions from transcribing DNA strands of transcriptionally active genes. Several
      NER factors undergo post-translational modifications, including ubiquitination,
      occurring swiftly and reversibly at DNA lesion sites. Accumulating evidence
      indicates that ubiquitination not only orchestrates the spatio-temporal
      recruitment of key protein factors to DNA lesion sites but also the productive
      assembly of NER pre-incision complex. This review will be restricted to the
      latest conceptual understanding of ubiquitin-mediated regulation of initial
      damage sensors of NER, that is DDB, XPC, RNAPII and CSB. We project hypothetical
      NER models in which ubiquitin-specific segregase, valosin-containing protein
      (VCP)/p97, plays an essential role in timely extraction of the congregated DNA
      damage sensors to functionally facilitate the DNA lesion elimination from the
      genome.

PMID- 27696489
TI  - 5th European Nursing Congress 4-7 October 2016, Rotterdam, the Netherlands,
      Caring for Older People: How Can We Do the Right Things Right?, Guest Editors:
      Johan Lambregts, Cuno van Merwijk, Bert de Groot.

PMID- 27696490
TI  - Response surface modelling of the pharmacodynamic interaction between propofol
      and remifentanil in patients undergoing anaesthesia.
AB  - This study describes the pharmacodynamic interaction between propofol and
      remifentanil. Sixty patients who were scheduled for elective surgery under
      general anaesthesia (30 males/30 females) were enrolled. Patients were randomly
      allocated to receive one of 15 combinations of drug levels. Baseline
      electroencephalograms (EEGs) were recorded for 5 minutes prior to administering
      the drugs. Patients received a target-controlled infusion at one of four
      predefined doses of propofol (high, 3 MUg/mL; medium, 1.5 MUg/mL; low, 0.5
      MUg/mL; or no drug) and of remifentanil (high, 6 or 8 ng/mL; medium, 4 ng/mL;
      low, 2 ng/mL; or no drug). The occurrence of muscle rigidity, apnoea, and loss of
      consciousness (LOC) was monitored, and EEGs were recorded during the drug
      administration phase. Electroencephalographic approximate entropy (ApEn) and
      temporal linear mode complexity (TLMC) parameters at baseline and under steady
      state conditions were calculated off-line. Response surfaces were developed to
      map the interaction between propofol and remifentanil to the probability of
      occurrence for quantal responses (muscle rigidity, apnoea, LOC) and ApEn and TLMC
      measurements. Model parameters were estimated using non-linear mixed effects
      modelling. The response surface revealed infra-additive and synergistic effects
      for muscle rigidity and apnoea, respectively. The effects of the combined drugs
      on LOC and EEG parameters (eg, ApEn and TLMC) were additive. The C50 estimates of
      remifentanil (ng/mL) and propofol (MUg/mL) were 9.11 and 130 000 for muscle
      rigidity, 8.99 and 6.26 for apnoea, 13.9 and 3.04 for LOC, 23.4 and 10.4 for
      ApEn, and 14.8 and 6.51 for TLMC, respectively. The probability of occurrence for
      muscle rigidity declined when propofol was combined with remifentanil.

PMID- 27696492
TI  - IIS 2015 Princeton Conference.

PMID- 27696491
TI  - Age and gender differences in self-control and its intergenerational
      transmission.
AB  - BACKGROUND: Few studies have been conducted in people of Asian descent that have
      reported to demonstrate the distinct developmental trends in good self-control
      and poor control. To fill this gap, we conducted a national cross-sectional
      survey among adolescents and young adults in China to further clarify the age and
      gender differences in self-control from a dual-systems perspective. METHODS: A
      total of 2910 adolescents (female, n = 1698) and their parents from five
      different provinces in China were surveyed using the Dual-Modes of Self-Control
      Scale (DMSC-S) and the Parents' Perceived Self-Control Scale. The mean age of the
      adolescent sample was 17.47 years (ranging from 12.50 to 25.42 years). RESULTS:
      Boys exhibited greater good self-control than girls. Poor control increased
      between 12 and 17 years of age and declined thereafter; however, good self
      control increased over the entire study period. Both good self-control and poor
      control in student participants were significantly associated with parents'
      perceived self-control; moreover, the association between good self-control and
      parental self-control was mediated by SES. CONCLUSION: The roles of age, gender,
      parental self-control and SES varied in a dual-systems model of self-control:
      good self-control and poor control. Implications of these results are discussed.

PMID- 27696493
TI  - Time trends in the health care burden and mortality of acute on chronic liver
      failure in the United States.
AB  - : Acute on chronic liver failure (ACLF) is associated with multisystem organ
      failure and poor prognosis in hospitalized patients with cirrhosis. We aimed to
      determine time trends in the epidemiology, economic burden, and mortality of ACLF
      in the United States. The National Inpatient Sample database was queried between
      2001 and 2011. ACLF was defined as two or more extrahepatic organ failures in
      patients with cirrhosis. The primary outcomes were trends in hospitalizations,
      hospital costs, and inpatient mortality. The number of hospitalizations for
      cirrhosis in the United States nearly doubled from 371,000 in 2001 to 659,000 in
      2011. The prevalence of ACLF among those hospitalizations increased from 1.5% (n
      = 5,400) to 5% (n = 32,300). The inpatient costs increased 2-fold for cirrhosis
      ($4.8 billion to $9.8 billion) and 5-fold ($320 million to $1.7 billion) for
      ACLF. In 2011, the cost per hospitalization for ACLF was 3.5-fold higher than
      that for cirrhosis ($53,570 versus $15,193). The in-hospital fatality rates
      decreased from 65% to 50% for ACLF and from 10% to 7% for cirrhosis. The organ
      failure trends in ACLF showed an increasing proportion of cardiovascular and
      cerebral and decreasing proportion of respiratory and renal failure. Age, male
      sex, and the number and types of organ failure were predictors of death in ACLF.
      CONCLUSION: Cirrhosis and ACLF represent a substantial and increasing health and
      economic burden in the United States; these data highlight an urgent need for
      research on pathophysiological mechanisms and effective therapy as well as for
      education of health care providers of its importance in the care of patients with
      cirrhosis. (Hepatology 2016;64:2165-2172).

PMID- 27696494
TI  - Muscle and nerve net organization in stalked jellyfish (Medusozoa: Staurozoa).
AB  - Staurozoan cnidarians display an unusual combination of polyp and medusa
      characteristics and their morphology may be informative about the evolutionary
      origin of medusae. We studied neuromuscular morphology of two staurozoans,
      Haliclystus 'sanjuanensis' and Manania handi, using whole mount
      immunohistochemistry with antibodies against FMRFamide and alpha-tubulin to label
      neurons and phalloidin to label muscles. All muscles appeared to lack striations.
      Longitudinal interradial muscles are probable homologues of stalk muscles in
      scyphopolyps, but in adult staurozoans they are elaborated to inwardly flex
      marginal lobes of the calyx during prey capture; these muscles are pennate in M.
      handi. Manubrial perradial muscles, like the manubrium itself, are an innovation
      shared with pelagic medusae and manubrial interradial muscles are shared with
      scyphozoan ephyra. Marginal muscles of M. handi displayed occasional synchronous
      contraction reminiscent of a medusa swim pulse, but contractions were not
      repetitive. The nerve net in both species showed regional variation in density
      and orientation of neurons. Some areas labeled predominantly by alpha-tubulin
      antibodies (exumbrellar epidermis), other areas labeled exclusively by FMRFamide
      antibodies (dense plexus of neurites surrounding the base of secondary tentacles,
      neuronal concentration at the base of transformed primary tentacles; gastrodermal
      nerve net), but most areas showed a mix of neurons labeled by these two
      antibodies and frequent co-labeling of neurons. Transformed primary tentacles had
      a concentration of FMRFamide-immunoreactive neurons at their base that was
      associated with a pigment spot in M. handi; this is consistent with their
      homology with rhopalia of medusae, which are also derived from primary tentacles.
      The muscular system of these staurozoans embodies characteristics of both
      scyphopolyps and pelagic medusae. However, their nerve net is more polyp-like,
      although marginal concentrations of the net associated with primary and secondary
      tentacles may facilitate the richer behavioral repertoire of staurozoans relative
      to polyps of other medusozoans. J. Morphol. 278:29-49, 2017. (c)(c) 2016 Wiley
      Periodicals,Inc.

PMID- 27696495
TI  - Quality of life decrements in men with prostate cancer undergoing androgen
      deprivation therapy.
AB  - OBJECTIVE: While androgen deprivation therapy (ADT) has been associated with
      decreased quality of life (QoL), controlled prospective studies are lacking. We
      aimed to assess QoL during ADT using two validated questionnaires and determine
      contributing factors. DESIGN: Prospective controlled study. PATIENTS: Sixty-three
      men with nonmetastatic prostate cancer newly commencing ADT (n = 34) and age- and
      radiotherapy-matched prostate cancer controls (n = 29). MEASUREMENTS: QoL was
      measured by Short-Form 12 version 2 survey (SF-12) and Aging Males' Symptoms
      (AMS) score at 0, 6 and 12 months. Generalized linear models determined the mean
      adjusted difference (MAD) (95% confidence interval) between groups during follow
      up. RESULTS: Compared to controls over 12 months, men receiving ADT had decreased
      SF-12 physical component score [MAD -3.61 (-6.94, -0.29), P = 0.013] reflecting
      worsening QoL but no change in the mental component (P = 0.74). Total AMS score
      increased [MAD 9.35 (5.65, 13.07), P < 0.001], reflecting worse QoL. Both SF-12
      and AMS changes were greater than reported minimum clinically important
      differences. AMS sub-domains showed increased somatic [MAD 3.96 (1.94, 5.99), P <
      0.001] and sexual [MAD 3.80 (2.16, 5.44), P < 0.001] components but not
      psychological (P = 0.19). Decrements were related to an increase in hot flushes
      (P = 0.016) but not haemoglobin decrease (P = 0.46). CONCLUSIONS: Within 12
      months, ADT is associated with clinically significant decreased QoL, particularly
      physical and sexual aspects, independent of the confounding effects of a cancer
      diagnosis or radiotherapy. As QoL is a crucial aspect of prostate cancer
      treatment, addressing hot flushes, sexual dysfunction and exercise may
      potentially improve outcomes for men undergoing ADT.

PMID- 27696496
TI  - Chemical gastritis and colitis related to hydrogen peroxide mouthwash.

PMID- 27696497
TI  - Cofactors-loaded quaternary structure of lysine-specific demethylase 5C (KDM5C)
      protein: Computational model.
AB  - The KDM5C gene (also known as JARID1C and SMCX) is located on the X chromosome
      and encodes a ubiquitously expressed 1560-aa protein, which plays an important
      role in lysine methylation (specifically reverses tri- and di-methylation of Lys4
      of histone H3). Currently, 13 missense mutations in KDM5C have been linked to X
      linked mental retardation. However, the molecular mechanism of disease is
      currently unknown due to the experimental difficulties in expressing such large
      protein and the lack of experimental 3D structure. In this work, we utilize
      homology modeling, docking, and experimental data to predict 3D structures of
      KDM5C domains and their mutual arrangement. The resulting quaternary structure
      includes KDM5C JmjN, ARID, PHD1, JmjC, ZF domains, substrate histone peptide,
      enzymatic cofactors, and DNA. The predicted quaternary structure was investigated
      with molecular dynamic simulation for its stability, and further analysis was
      carried out to identify features measured experimentally. The predicted structure
      of KDM5C was used to investigate the effects of disease-causing mutations and it
      was shown that the mutations alter domain stability and inter-domain
      interactions. The structural model reported in this work could prompt
      experimental investigations of KDM5C domain-domain interaction and exploration of
      undiscovered functionalities. Proteins 2016; 84:1797-1809. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27696498
TI  - Evaluation of the revised New Zealand national newborn screening protocol for
      congenital hypothyroidism.
AB  - OBJECTIVE: The aim of this study was to assess the performance of the revised New
      Zealand (NZ) newborn screening TSH cut-offs for congenital hypothyroidism (CHT).
      METHODS: Screening data over 24 months were obtained from the NZ newborn
      metabolic screening programme, which utilizes a 2-tier system of direct clinical
      referral for infants with markedly elevated TSH, and second samples from those
      with mild TSH elevation. We evaluated the impact of a reduced TSH threshold (50
      to 30 mIU/l blood) for direct notification and a lower cut-off (15 to 8 mIU/l
      blood) applied to second samples and babies older than 14 days. RESULTS: In 2013
      and 2014, 117 528 infants underwent newborn screening for CHT. Fifty-two CHT
      cases were identified by screening (47 general newborn population, five repeat
      testing in low-birth-weight infants) and one case was missed. Thirty-two infants
      with screening TSH >=30 mIU/l were directly referred at a median of 9 days (5-14)
      and 15 with TSH 15-29 mIU/l were referred after a second sample at a median of 20
      days (9-52, P < 0.001). All directly referred infants were confirmed as CHT cases
      with no earlier referrals as a result of the reduced threshold. The lower TSH cut
      off applied to second samples lead to the identification of six extra cases of
      CHT (15% increase) from seven extra clinical referrals. CONCLUSIONS: The NZ
      screening programme achieved a 15% increase in CHT case detection for minimal
      increase in workload or anxiety for families of healthy infants. A further
      decrease in the threshold for direct referral may allow earlier diagnoses.

PMID- 27696499
TI  - Mohit's Pharmakon: Symptom, Rotational Bodies, and Pharmaceuticals in Rural
      Rajasthan.
AB  - This article reexamines medical anthropology theories of symptom, illness, and
      disease to consider unregulated medical care in India. It builds on clinical
      observations, an inventory of the pharmaceuticals used by men who call themselves
      "Bengali doctors," and their patients to understand medical care in a context
      that privileges symptom not disease. It draws on Derrida's use of pharmakon to
      outline the complexities of care and embodiment and helps locate local and
      medical anthropology theories of symptom and pharmaceuticals within theories of
      the experiential body. It asks two key questions: What is medical care without
      disease and what are its implications on a local biology in which disease-based
      biomedicine is modified? Searching for a tentative answer, it works to bring
      medical anthropology's interest in symptom back to the body without losing
      symptoms' connection to political economies, individual experience, and localized
      biomedicine.

PMID- 27696500
TI  - The rs2274911 polymorphism in GPRC6A gene is associated with insulin resistance
      in normal weight and obese subjects.
AB  - OBJECTIVE: Identification of the novel endocrine role of osteocalcin (OC) and its
      receptor GPRC6A has given rise to a new branch of research in OC/GPRC6A axis
      related to glucose metabolism. GPRC6A- and OC-deficient mice share features of
      the metabolic syndrome, in addition to male infertility. Recently, the
      polymorphism rs2274911 in GPRC6A was shown to be associated with testicular
      impairment. We aimed to investigate the role of rs2274911 polymorphism in glucose
      and lipid metabolism in a cohort of normal weight and obese subjects DESIGN,
      PATIENTS, SETTINGS: A total of 392 male and females, including 218 obese patients
      and 174 age-matched normal weight controls, were retrospectively selected.
      RESULTS: The distribution of rs2274911 alleles and genotypes did not differ
      either between normal weight and obese subjects or sexes (all P > 0.05). Age- and
      OC-adjusted multivariate analysis revealed that, in the normal weight group,
      fasting insulin and HOMA-IR increased in GA (P = 0.016 and P = 0.025) and AA
      genotypes (P = 0.033 and P = 0.040) compared with GG homozygotes. In the obese
      group, AA homozygotes had increased fasting glucose (P = 0.041 vs GG).
      Triglycerides, fasting insulin and HOMA-IR increased in both GA (P = 0.020, P <
      0.001 and P = 0.001) and AA genotype (P = 0.021, P = 0.013 and P = 0.013).
      CONCLUSION: In a cohort of normal weight and obese subjects, we found that the
      nonrare polymorphism rs2274911 in the GPRC6A gene was associated with insulin
      resistance features, independently of the metabolic phenotype and OC levels.

PMID- 27696501
TI  - Inhibition of SLC7A11 by Sulfasalazine Enhances Osteogenic Differentiation of
      Mesenchymal Stem Cells by Modulating BMP2/4 Expression and Suppresses Bone Loss
      in Ovariectomized Mice.
AB  - An imbalance in osteogenesis and adipogenesis is a crucial pathological factor in
      the development of osteoporosis. Many attempts have been made to develop drugs to
      prevent and treat this disease. In the present study, we investigated the
      phenomenon whereby downregulation of SLC7A11 significantly enhanced the
      osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro, and
      promoted the bone formation in vivo. Sulfasalazine (SAS), an inhibitor of
      SLC7A11, increased the osteogenic potential effectively. Mechanistically,
      inhibition of SLC7A11 by SAS treatment or knockdown of SLC7A11 increased BMP2/4
      expression dramatically. In addition, we detected increased Slc7a11 expression in
      bone marrow MSCs of ovariectomized (OVX) mice. Remarkably, SAS treatment
      attenuated bone loss in ovariectomized mice. Together, our data suggested that
      SAS could be used to treat osteoporosis by enhancing osteogenic differentiation
      of MSCs. (c) 2016 American Society for Bone and Mineral Research.

PMID- 27696502
TI  - High and low vitamin D level is associated with cardiovascular autonomic
      neuropathy in people with Type 1 and Type 2 diabetes.
AB  - AIM: To investigate the possible association between vitamin D deficiency and
      cardiovascular autonomic neuropathy in people with diabetes. METHODS: A total of
      113 people with Type 1 or Type 2 diabetes [mean (interquartile range) diabetes
      duration 22.0 (12-31) years, mean (sd) age 56.2 (13.0) years, 58% men] underwent
      vitamin D (D2 and D3) assessment, and were screened for cardiovascular autonomic
      neuropathy using three cardiovascular reflex tests [heart rate response to deep
      breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva manoeuvre]
      and assessment of 5-min resting heart rate and heart rate variability indices.
      RESULTS: We found an inverse U-shaped association between serum vitamin D level
      and E/I ratio, 30/15 ratio and three heart rate variability indices (P < 0.05).
      Vitamin D level was non-linearly associated with cardiovascular autonomic
      neuropathy diagnosis (P < 0.05 adjusted for age and sex). Linear regression
      models showed that an increase in vitamin D level from 25 to 50 nmol/l was
      associated with an increase of 3.9% (95% CI 0.1;7.9) in E/I ratio and 4.8% (95%
      CI 4.7;9.3) in 30/15 ratio. Conversely, an increase from 125 to 150 nmol/l in
      vitamin D level was associated with a decrease of 2.6% (95% CI -5.8;0.1) and 4.1%
      (95% CI -5.8;-0.5) in the respective outcome measures. CONCLUSIONS: High and low
      vitamin D levels were associated with cardiovascular autonomic neuropathy in
      people with diabetes. Future studies should explore this association and the
      efficacy of treating dysvitaminosis D to prevent cardiovascular autonomic
      neuropathy.

PMID- 27696503
TI  - Child behaviour problems and childhood illness: development of the Eczema
      Behaviour Checklist.
AB  - BACKGROUND/OBJECTIVES: Children with atopic dermatitis are at increased risk of
      both general behaviour problems, and those specific to the condition and its
      treatment. This can hamper the ability of parents to carry out treatment and
      manage the condition effectively. To date, there is no published instrument
      available to assess child behaviour difficulties in the context of atopic
      dermatitis management. Our aim was to develop a reliable and valid instrument to
      assess atopic dermatitis-specific child behaviour problems, and parents' self
      efficacy (confidence) for managing these behaviours. METHODS: The Eczema
      Behaviour Checklist (EBC) was developed as a 25-item questionnaire to measure (i)
      extent of behaviour problems (EBC Extent scale), and (ii) parents' self-efficacy
      for managing behaviour problems (EBC Confidence scale), in the context of child
      atopic dermatitis management. A community-based sample of 292 parents completed
      the EBC, measures of general behaviour difficulties, self-efficacy with atopic
      dermatitis management and use of dysfunctional parenting strategies. RESULTS:
      There was satisfactory internal consistency and construct validity for EBC Extent
      and Confidence scales. There was a negative correlation between atopic dermatitis
      specific behaviour problems and parents' self-efficacy for dealing with
      behaviours (r = -.53, p < .001). Factor analyses revealed a three-factor
      structure for both scales: (i) treatment-related behaviours; (ii) symptom-related
      behaviours; and (iii) behaviours related to impact of the illness. Variation in
      parents' self-efficacy for managing their child's atopic dermatitis was explained
      by intensity of illness-specific child behaviour problems and parents' self
      efficacy for dealing with the behaviours. CONCLUSIONS: The new measure of atopic
      dermatitis-specific child behaviour problems was a stronger predictor of parents'
      self-efficacy for managing their child's condition than was the measure of
      general child behaviour difficulties. Results provide preliminary evidence of
      reliability and validity of the EBC, which has potential for use in clinical and
      research settings, and warrant further psychometric evaluation.

PMID- 27696504
TI  - Green tea polyphenols require the mitochondrial iron transporter, mitoferrin, for
      lifespan extension in Drosophila melanogaster.
AB  - Green tea has been found to increase the lifespan of various experimental animal
      models including the fruit fly, Drosophila melanogaster. High in polyphenolic
      content, green tea has been shown to reduce oxidative stress in part by its
      ability to bind free iron, a micronutrient that is both essential for and toxic
      to all living organisms. Due to green tea's iron-binding properties, we
      questioned whether green tea acts to increase the lifespan of the fruit fly by
      modulating iron regulators, specifically, mitoferrin, a mitochondrial iron
      transporter, and transferrin, found in the hemolymph of flies. Publicly available
      hypomorph mutants for these iron regulators were utilized to investigate the
      effect of green tea on lifespan and fertility. We identified that green tea could
      not increase the lifespan of mitoferrin mutants but did rescue the reduced male
      fertility phenotype. The effect of green tea on transferrin mutant lifespan and
      fertility were comparable to w1118 flies, as observed in our previous studies, in
      which green tea increased male fly lifespan and reduced male fertility.
      Expression levels in both w1118 flies and mutant flies, supplemented with green
      tea, showed an upregulation of mitoferrin but not transferrin. Total body and
      mitochondrial iron levels were significantly reduced by green tea supplementation
      in w1118 and mitoferrin mutants but not transferrin mutant flies. Our results
      demonstrate that green tea may act to increase the lifespan of Drosophila in part
      by the regulation of mitoferrin and reduction of mitochondrial iron.

PMID- 27696505
TI  - Effectiveness of Africa's tropical protected areas for maintaining forest cover.
AB  - The effectiveness of parks for forest conservation is widely debated in Africa,
      where increasing human pressure, insufficient funding, and lack of management
      capacity frequently place significant demands on forests. Tropical forests house
      a substantial portion of the world's remaining biodiversity and are heavily
      affected by anthropogenic activity. We analyzed park effectiveness at the
      individual (224 parks) and national (23 countries) level across Africa by
      comparing the extent of forest loss (as a proxy for deforestation) inside parks
      to matched unprotected control sites. Although significant geographical variation
      existed among parks, the majority of African parks had significantly less forest
      loss within their boundaries (e.g., Mahale Park had 34 times less forest loss
      within its boundary) than control sites. Accessibility was a significant driver
      of forest loss. Relatively inaccessible areas had a higher probability (odds
      ratio >1, p < 0.001) of forest loss but only in ineffective parks, and relatively
      accessible areas had a higher probability of forest loss but only in effective
      parks. Smaller parks less effectively prevented forest loss inside park
      boundaries than larger parks (T = -2.32, p < 0.05), and older parks less
      effectively prevented forest loss inside park boundaries than younger parks
      (F2,154 = -4.11, p < 0.001). Our analyses, the first individual and national
      assessment of park effectiveness across Africa, demonstrated the complexity of
      factors (such as geographical variation, accessibility, and park size and age)
      influencing the ability of a park to curb forest loss within its boundaries.

PMID- 27696506
TI  - Echocardiographic assessment of right ventricular contractile reserve in healthy
      subjects.
AB  - BACKGROUND: Exercise-induced increase in pulmonary artery systolic pressure
      (PASP) as a possible measure of right ventricular (RV) contractile reserve has
      been shown to predict survival in severe pulmonary hypertension. However, RV
      contractile reserve can also be measured by changes in stroke volume (SV),
      tricuspid annular plane systolic excursion (TAPSE), or tricuspid annular systolic
      velocity (S'). The limits of normal values and the functional significance of
      these changes in healthy subjects are not well known. METHODS: In this
      prospective study, 90 healthy subjects (45 male, mean age 39 +/- 13 years)
      underwent exercise stress echocardiography with measurement of TAPSE, S',
      TAPSE/PASP, SV, and PASP at rest and peak exercise. Maximum and minimum normal
      values were reported for all indices. RESULTS: Normal values of exercise-induced
      changes (Delta) were 4 to 10 mm for TAPSE, 6 to 14 cm/s for S', 12 to 57 mm Hg
      for PASP, 0 to 96 mL for SV, and -1.2 to 0 mm/mm Hg for TAPSE/PASP. At peak
      exercise, women showed lower DeltaTAPSE/PASP, DeltaPASP, DeltaS', and DeltaSV,
      but higher TAPSE/PASP than men. Aging was associated with decreased
      DeltaTAPSE/PASP, DeltaTAPSE, DeltaS', DeltaPASP, and DeltaSV. In addition,
      DeltaS', DeltaTAPSE/PASP, DeltaPASP, and DeltaSV, but not DeltaTAPSE, were
      directly correlated with maximum workload. CONCLUSIONS: Our results provide age-
      and sex-related limits of normal for RV contractile reserve as assessed by
      exercise stress echocardiography and demonstrate that RV systolic function
      indices (PASP, TAPSE, S', and TAPSE/PASP) correlate with maximum exercise
      capacity.

PMID- 27696507
TI  - The impact of trunk impairment on performance-determining activities in
      wheelchair rugby.
AB  - In Paralympic sport, classification of impairment is needed to prevent a one
      sided and predictable outcome of competition, in which the least impaired athlete
      has the best chance to win. To develop evidence-based classification in
      wheelchair rugby, the impact of trunk impairment, measured by the Trunk
      Impairment Classification (TIC), on performance-determining activities was
      assessed. Arm impairment was analyzed as a covariant. Fifty-five athletes, 21
      with TIC score 0, 13 with TIC score 0.5, 11 with TIC score 1.0, and 10 with TIC
      score 1.5 performed standardized sport-specific activities. A multiple step
      forward regression analysis was performed for all activities to assess the
      relative impact of trunk and arm impairment on performance. Trunk impairment was
      the most important factor for tilting the chair and acceleration in the first 2
      m. The explained variance of the performance by trunk and arm impairment ranged
      from 23% for acceleration in the first meter, to 37% for sprint momentum, the
      tilt test left, and the time to cover 3 and 4 m. This study shows that athletes
      with limited trunk impairment are more proficient in wheelchair rugby than
      athletes with severe trunk impairment.

PMID- 27696508
TI  - Analysis of synonymous codon usage patterns in the edible fungus Volvariella
      volvacea.
AB  - In this study, trends in synonymous codons usage of Volvariella volvecea have
      been first examined by analysis of complete coding sequences and gene chip data.
      The results showed that GC content at three codon positions are obviously
      different and there were several factors shaping the codon usage of V. volvacea
      genes, including base composition. The comparison of codon usage among four
      edible fungi such as V. volvacea, Agaricus bisporus, Coprinopsis cinerea, and
      Pleurotus ostreatus indicated that the similar codon usage pattern was used among
      V. volvacea, A. bisporus and P. ostreatus, but there was significantly different
      codon usage pattern of C. cinerea. Two arrays of optimal codons were determined
      by effective number of codons (ENC) values and gene chip database separately,
      resulting that most of the ENC-predicted optimal codons were included in the
      array of gene chip resulted optimal codons. This study can provide useful
      information for codon usage pattern analysis and gene transformation of V.
      volvacea.

PMID- 27696509
TI  - Inhibitory effect of 660-nm LED on melanin synthesis in in vitro and in vivo.
AB  - BACKGROUND: Skin hyperpigmentary disorders including postinflammatory
      hyperpigmentation, melasma, solar lentigines, and conditions like freckles are
      common. The light-emitting diodes (LEDs) are the latest category of nonthermal
      and noninvasive phototherapy to be considered in skin pigmentation disorder
      treatment. PURPOSE: The purpose of this study was to investigate the effects of
      660-nm LED on inhibition of melanogenesis. We investigated whether a 660-nm LED
      affected melanin synthesis in in vitro and in vivo models, and we explored the
      mechanisms involved. METHODS: The inhibitory effect of 660-nm LED on melanin
      synthesis was evaluated in B16F10 cells and HRM-2 melanin-possessing hairless
      mice were used to evaluate the antimelanogenic effects of 660-nm LED. RESULTS:
      Interestingly, 660-nm LED inhibited alpha-melanocyte-stimulating hormone-induced
      tyrosinase activity in B16F10 cells. We also found that 660-nm LED decreased MITF
      and tyrosinase expression and induced the activation of ERK. These findings
      suggest that the depigmenting effects of 660-nm LED result from downregulation of
      MITF and tyrosinase expression due to increased ERK activity. The 660-nm LED
      reduced UVB-induced melanogenesis in the skin of HRM-2 via downregulation of
      tyrosinase and MITF. CONCLUSION: These findings suggest 660-nm LED is a
      potentially depigmentation strategy.

PMID- 27696510
TI  - Response and recovery of the macrophytes Elodea canadensis and Myriophyllum
      spicatum following a pulse exposure to the herbicide iofensulfuron-sodium in
      outdoor stream mesocosms.
AB  - Interest in stream mesocosms has recently revived for higher tier aquatic
      macrophyte risk assessment of plant protection products mainly because 1) the
      highest predicted environmental concentrations for the assessment of effects are
      frequently derived from stream scenarios, and 2) they allow an effect assessment
      using stream-typical pulse exposures. Therefore, the present stream mesocosm
      study used an herbicide pulse exposure and evaluated the responses of Elodea
      canadensis and Myriophyllum spicatum. Macrophytes were exposed for 24 h to 1
      MUg/L, 3 MUg/L, 10 MUg/L, and 30 MUg/L of the herbicide iofensulfuron-sodium with
      a subsequent recovery period of 42 d. Biological endpoints were growth rates of
      the main, side, and total shoot length, the shoot number, the maximum root
      length, and the dry weight. The total shoot length was identified as the most
      sensitive endpoint; the growth rate of the total shoot length was inhibited by up
      to 66% and 45% in M. spicatum and E. canadensis, respectively. The lowest no
      observed effect concentrations (NOECs) were observed at day 7 and/or day 14 after
      herbicide treatment and were 1 MUg/L for M. spicatum and 3 MUg/L for E.
      canadensis. The no-observed-ecologically-adverse-effect concentrations (NOEAECs)
      were 10 MUg/L and 30 MUg/L for M. spicatum and E. canadensis, respectively. Such
      or similar mesocosm designs are useful to simulate typical stream exposures and
      estimate herbicide effects on aquatic macrophytes in stream systems. Environ
      Toxicol Chem 2017;36:1090-1100. (c) 2016 SETAC.

PMID- 27696511
TI  - The long noncoding RNA-ROR promotes the resistance of radiotherapy for human
      colorectal cancer cells by targeting the p53/miR-145 pathway.
AB  - BACKGROUND AND AIM: Long intergenic noncoding RNAs (lincRNAs) have critical roles
      in elevating efficacy of anticancer therapy and tumor progression. Recent studies
      show that Regulator of Reprogramming (ROR) is aberrantly expressed in several
      types of cancer, including colorectal cancer (CRC). Radiotherapy is considered as
      a standard preoperative treatment. However, a considerable number of CRCs are
      resistant to radiotherapy. In this study, we evaluated the role of lincRNA-ROR in
      radiotherapy for CRC and detected the underlying molecular mechanism. METHODS:
      Real-time polymerase chain reaction was employed to quantify the expression level
      of lincRNA-ROR in different CRC cell lines and tissue samples. Cell viability and
      apoptosis assays were used to confirm the radiotherapy-mediated effects by
      lincRNA-ROR altered expression. The direct impact of lincRNA-ROR on the
      expression of p53/miR-145 by loss-of-function and gain-of-function strategy was
      also analyzed. A xenograft mouse model was used to evaluate the role of linc-ROR
      in CRC treatment. RESULTS: We discovered that lincRNA-ROR was upregulated in CRC
      cell lines and tissue samples. We further showed that knockdown of lincRNA-ROR
      enhanced the sensitivity to radiotherapy for CRC by inhibiting cell viability and
      promoting apoptosis. Activity of the p53/miR-145 pathway may help explain the
      role of lincRNA-ROR for stress-induced regulation in CRC therapy. Combined
      specific knockdown of lincRNA-ROR and radiotherapy treatment in xenograft model
      resulted in a significant reduction in the tumor growth. CONCLUSION: LincRNA-ROR
      decreases sensitivity to radiotherapy via the negative regulation of p53/miR-145
      and may represent a potential target for the treatment of CRC.

PMID- 27696512
TI  - Melatonin prevents deregulation of the sphingosine kinase/sphingosine 1-phosphate
      signaling pathway in a mouse model of diethylnitrosamine-induced hepatocellular
      carcinoma.
AB  - The sphingosine kinase (SphK)/sphingosine 1-phosphate (S1P) pathway is involved
      in multiple biological processes, including carcinogenesis. Melatonin shows
      beneficial effects in cell and animal models of hepatocellular carcinoma, but it
      is unknown if they are associated with the modulation of the SphK/S1P system,
      along with different downstream signaling pathways modified in cancer. We
      investigated the effects of melatonin in mice which received diethylnitrosamine
      (DEN) (35 mg/kg body weight i.p) once a week for 8 weeks. Melatonin was given at
      5 or 10 mg/kg/day i.p. beginning 4 weeks after the onset of DEN administration
      and ending at the sacrifice time (10, 20, 30, or 40 weeks). Melatonin alleviated
      the distortion of normal hepatic architecture, lowered the incidence of
      preneoplastic/neoplastic lesions, and inhibited the expression of
      proliferative/cell cycle regulatory proteins (Ki67, PCNA, cyclin D1, cyclin E,
      CDK4, and CDK6). S1P levels and expression of SphK1, SphK2, and S1P receptors
      (S1PR1/S1PR3) were significantly elevated in DEN-treated mice. However, there was
      a decreased expression of S1P lyase. These effects were significantly abrogated
      in a time- and dose-dependent manner by melatonin, which also increased S1PR2
      expression. Following DEN treatment, mice exhibited increased phosphorylation of
      PI3K, AKT, mTOR, STAT3, ERK, and p38, and a higher expression of NF-kappaB p50
      and p65 subunits. Melatonin administration significantly inhibited those changes.
      Data obtained suggest a contribution of the SphK/S1P system and related signaling
      pathways to the protective effects of melatonin in hepatocarcinogenesis.

PMID- 27696513
TI  - Is there an optimal preoperative management strategy for
      phaeochromocytoma/paraganglioma?
AB  - Phaeochromocytomas and paragangliomas (PPGLs) are catecholamine secreting
      neuroendocrine tumours that predispose to haemodynamic instability. Currently,
      surgery is the only available curative treatment, but carries potential risks
      including hypertensive and hypotensive crises, cardiac arrhythmias, myocardial
      infarction and stroke, due to tumoral release of catecholamines during
      anaesthetic induction and tumour manipulation. The mortality associated with
      surgical resection of PPGL has significantly improved from 20-45% in the early
      20th century (Apgar & Papper, AMA Archives of Surgery, 1951, 62, 634) to 0-2.9%
      in the early 21st century (Kinney et al. Journal of Cardiothoracic and Vascular
      Anesthesia, 2002, 16, 359), largely due to availability of effective
      pharmacological agents and advances in surgical and anaesthetic practice.
      However, surgical resection of PPGL still poses significant clinical management
      challenges. Preoperatively, alpha-adrenoceptor blockade is the mainstay of
      management, although various pharmacological strategies have been proposed, based
      largely on reports derived from retrospective data sets. To date, no consensus
      has been reached regarding the 'ideal' preoperative strategy due, in part, to a
      paucity of data from high-quality evidence-based studies comparing different
      treatment regimens. Here, based on the available literature, we address the
      Clinical Question: Is there an optimal preoperative management strategy for PPGL?

PMID- 27696514
TI  - WEO position statement on hygiene in digestive endoscopy: Focus on endoscopy
      units in Asia and the Middle East.
AB  - The aim of this position statement is to reinforce the key points of hygiene in
      digestive endoscopy. The present article details the minimum hygiene requirements
      for reprocessing of endoscopes and endoscopic devices, regardless of the
      reprocessing method (automated washer-disinfector or manual cleaning) and the
      endoscopy setting (endoscopy suite, operating room, elective or emergency
      procedures). These minimum requirements are mandatory for patient safety. Both
      advanced diagnostic and therapeutic endoscopies should be carried out in an
      environment that is safe for patients and staff. Particular attention is given to
      contaminants. Procedural errors in decontamination, defective equipment, and
      failure to follow disinfection guidelines are major factors contributing to
      transmission of infection during endoscopy. Other important risk factors include
      inadequate cleaning, use of older endoscopes with surface and working channel
      irregularities, and contamination of water bottles or irrigating solutions.
      Infections by multidrug-resistant organisms have become an increasing problem in
      health-care systems worldwide. Since 2010, outbreaks of multidrug-resistant
      bacteria associated with endoscopic retrograde cholangiopancreatography have been
      reported from the USA, France, Germany, and The Netherlands. In many endoscopy
      units in Asia and the Middle East, reprocessing procedures have lagged behind
      those of Western countries for cultural reasons or lack of financial resources.
      This inconsistency in standards is now being addressed, and the World Endoscopy
      Organization has prepared this position statement to highlight key points for
      quality assurance in any endoscopy unit in any country.

PMID- 27696516
TI  - Fish bioconcentration studies with column-generated analyte concentrations of
      highly hydrophobic organic chemicals.
AB  - The performance of aqueous exposure bioconcentration fish tests according to
      Organisation for Economic Co-operation and Development (OECD) guideline 305
      requires the possibility of preparing stable aqueous concentrations of the test
      substances. For highly hydrophobic organic chemicals (HOCs; octanol-water
      partition coefficient [log KOW ] > 5), testing via aqueous exposure may become
      increasingly difficult. A solid-phase desorption dosing system was developed to
      generate stable concentrations of HOCs without using solubilizing agents. The
      system was tested with hexachlorobenzene (HCB), o-terphenyl (oTP),
      polychlorinated biphenyl (PCB) 153, and dibenz[a,h]anthracene (DBA) (log KOW 5.5
      7.8) in 2 flow-through fish tests with rainbow trout (Oncorhynchus mykiss). The
      analysis of the test media applied during the bioconcentration factor (BCF)
      studies showed that stable analyte concentrations of the 4 HOCs were maintained
      in the test system over an uptake period of 8 wk. Bioconcentration factors (L kg
      1 wet wt) were estimated for HCB (BCF 35 589), oTP (BCF 12 040), and PCB 153 (BCF
      18 539) based on total water concentrations. No bioconcentration could be
      determined for DBA, probably because of the rapid metabolism of the test item.
      The solid-phase desorption dosing system is suitable to provide stable aqueous
      concentrations of HOCs required to determine the bioconcentration in fish and
      represents a viable alternative to the use of solubilizing agents for the
      preparation of test solutions. Environ Toxicol Chem 2017;36:906-916. (c) 2016 The
      Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals,
      Inc. on behalf of SETAC.

PMID- 27696515
TI  - Bioaccumulation and trophodynamics of the antidepressants sertraline and
      fluoxetine in laboratory-constructed, 3-level aquatic food chains.
AB  - Although reports of pharmaceutical bioconcentration in aquatic organisms are
      increasing, less is known about trophic transfer in aquatic food webs. The
      bioaccumulation and trophodynamics of sertraline and fluoxetine, 2 selective
      serotonin reuptake inhibitors (SSRIs) frequently detected in aquatic
      environments, were tested by exposing constructed aquatic food chains to SSRIs
      under controlled laboratory conditions. Both of these ionizable, weak base
      pharmaceuticals showed lower bioaccumulation factors (BAFs) with increasing
      trophic level (i.e., no biomagnifications) in 2 3-level food chains (Acer
      platanoides, fed to Asellus aquaticus, in turn fed to Notonecta glauca or
      Pungitius pungitius). Mean sertraline BAFs in A. platanoides, A. aquaticus, N.
      glauca, and P. pungitus were 2200 L/kg, 360 L/kg, 26 L/kg, and 49 L/kg,
      respectively, and mean fluoxetine BAFs 1300 L/kg, 110 L/kg, 11 L/kg, and 41 L/kg,
      respectively. The weak influence of diet was further demonstrated by measured
      BAFs being equal to or lower than measured bioconcentration factors (BCFs).
      Organism lipid content was not positively correlated with BAFs, suggesting that
      other processes are driving interspecific differences in SSRI bioaccumulation.
      The empirically derived parameter values were introduced into a proposed
      bioaccumulation model, and a poor correlation was found between modeled and
      empirical BAFs (predicted r2  = -0.63). In conclusion, the apparent lack of
      biomagnification of these ionizable pharmaceuticals suggests that environmental
      concern should not necessarily focus only on higher trophic levels, but also on
      species showing high BCFs at any trophic level. Environ Toxicol Chem 2017;36:1029
      1037. (c) 2016 SETAC.

PMID- 27696517
TI  - CD38, BCL-2, PD-1, and PD-1L expression in nodal peripheral T-cell lymphoma:
      Possible biomarkers for novel targeted therapies?

PMID- 27696518
TI  - Mitigation of B1+ inhomogeneity using spatially selective excitation with jointly
      designed quadratic spatial encoding magnetic fields and RF shimming.
AB  - PURPOSE: The inhomogeneity of flip angle distribution is a major challenge
      impeding the application of high-field MRI. We report a method combining
      spatially selective excitation using generalized spatial encoding magnetic fields
      (SAGS) with radiofrequency (RF) shimming to achieve homogeneous excitation. This
      method can be an alternative approach to address the challenge of B1+
      inhomogeneity using nonlinear gradients. METHODS: We proposed a two-step
      algorithm that jointly optimizes the combination of nonlinear spatial encoding
      magnetic fields and the combination of multiple RF transmitter coils and then
      optimizes the locations, RF amplitudes, and phases of the spokes. RESULTS: Our
      results show that jointly designed SAGS and RF shimming can provide a more
      homogeneous flip angle distribution than using SAGS or RF shimming alone.
      Compared with RF shimming alone, our approach can reduce the relative standard
      deviation of flip angle by 56% and 52% using phantom and human head data,
      respectively. CONCLUSION: The jointly designed SAGS and RF shimming method can be
      used to achieve homogeneous flip angle distributions when fully parallel RF
      transmission is not available. Magn Reson Med 78:577-587, 2017. (c) 2016
      International Society for Magnetic Resonance in Medicine.

PMID- 27696519
TI  - ALBI and PALBI grade predict survival for HCC across treatment modalities and
      BCLC stages in the MELD Era.
AB  - BACKGROUND AND AIM: The severity of liver dysfunction in hepatocellular carcinoma
      (HCC) is often estimated with Child-Turcotte-Pugh (CTP) classification or model
      for end-stage liver disease (MELD) score. We aim to investigate the performance
      of albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grade, which
      are recently reported to be simple and objective measurements for liver reserve
      in HCC. METHODS: Between 2002 and 2014, consecutive 3182 HCC patients were
      enrolled to follow up their survival. The area under receiver-operator
      characteristic curve (AUC) was calculated to test the discriminatory powers over
      1-year, 3-year, and 5-year survival. RESULTS: Significant survival differences
      were found across all ALBI and PALBI grades (both P < 0.001). The majority (73%)
      of patients were CTP class A. Within CTP class A, ALBI revealed two prognostic
      groups while PALBI segregated three prognostic groups. The PABLI grade also
      identified three different survival groups for patients undergoing resection,
      ablation, and chemoembolization. Both ALBI and PALBI grade were capable of
      discerning survival among different HCC stages. The PALBI grade had significantly
      higher AUC compared with CTP classification and ALBI grade at 1, 3, and 5 years.
      For CTP class A patients, the PALBI grade was also associated with significantly
      higher AUC compared with ALBI grade at 1-year and 3-year intervals. The MELD
      score has the lowest AUC compared with other systems. CONCLUSIONS: Both ALBI and
      PALBI grade are adequate models to assess liver dysfunction in HCC. The PALBI
      grade is consistently better in all patients, in patients with minimally
      decreased liver function, and in patients receiving different aggressive
      therapies.

PMID- 27696520
TI  - Psychological outcomes of evening and night closed-loop insulin delivery under
      free living conditions in people with Type 1 diabetes: a 2-month randomized
      crossover trial.
AB  - AIM: To assess the impact on fear of hypoglycaemia and treatment satisfaction
      with an artificial pancreas system used for 2 consecutive months, as well as
      participant acceptance of the artificial pancreas system. METHODS: In a
      randomized crossover trial patient-related outcomes associated with an evening
      and-night artificial pancreas and sensor-augmented pump therapy were compared.
      Both intervention periods lasted 8 weeks. The artificial pancreas acceptance
      questionnaire (range 0-90, higher scores better), Hypoglycaemia Fear Survey II
      (range 0-72, higher scores worse) and Diabetes Treatment Satisfaction
      Questionnaire (range 0-36, higher scores better) were completed by 32
      participants. Semi-structured interviews were conducted after study completion in
      a subset of six participants. Outcomes were compared using a repeated-measures
      anova model or paired t-test when appropriate. RESULTS: The total artificial
      pancreas acceptance questionnaire score at the end of the artificial pancreas
      period was 69.1 (sd 14.7; 95% CI 63.5, 74.7), indicating a positive attitude
      towards the artificial pancreas. No significant differences were found among the
      scores at baseline, end of sensor-augmented pump therapy period or end of the
      artificial pancreas period with regard to fear of hypoglycaemia [28.2 (sd 17.5),
      23.5 (sd 16.6) and 23.5 (sd 16.7), respectively; P = 0.099] or diabetes treatment
      satisfaction [29.0 (sd 3.9), 28.2 (sd 5.2) and 28.0 (sd 7.1), respectively; P =
      0.43]. Themes frequently mentioned in the interviews were 'positive effects at
      work', 'improved blood glucose', 'fewer worries about blood glucose', but also
      'frequent alarms', 'technological issues' and 'demand for an all-in-one device'.
      CONCLUSIONS: The psychological outcomes of artificial pancreas and sensor
      augmented pump therapy were similar. Current artificial pancreas technology is
      promising but user concerns should be taken into account to ensure utility of
      these systems.

PMID- 27696522
TI  - Parameters of Context-Induced Ethanol (EtOH)-Seeking in Alcohol-Preferring (P)
      Rats: Temporal Analysis, Effects of Repeated Deprivation, and EtOH Priming
      Injections.
AB  - BACKGROUND: Drug-paired environments can act as stimuli that elicit drug craving.
      In humans, drug craving is influenced by the amount of time abstinent, number of
      past periods of abstinence, and inadvertent exposure to the previously abused
      drug. The current experiments were designed to determine the effects of (i) the
      duration of abstinence on expression of ethanol (EtOH)-seeking; (ii) EtOH priming
      following a short and long abstinence period; and (iii) repeated deprivation
      cycles on relapse drinking and EtOH-seeking. METHODS: Rats were allowed to self
      administer 15% EtOH, processed through extinction training, maintained in a home
      cage for a designated EtOH-free period, and then reintroduced to the operant
      context in the absence of EtOH. The experiments examined the effects of: (i)
      various home-cage duration periods (1 to 8 weeks), (ii) priming injections of
      EtOH in the Pavlovian spontaneous recovery (PSR; 14 days after extinction) and
      reinstatement of responding (RoR; 1 day after extinction) models, and (iii)
      exposure to repeated cycles of EtOH access-deprivation on relapse drinking and
      EtOH-seeking behavior. RESULTS: Highest expression of EtOH-seeking was observed
      following 6 weeks of home-cage maintenance. Priming injections of EtOH were more
      efficacious at stimulating/enhancing EtOH-seeking in the PSR than RoR model.
      Exposure to repeated cycles of EtOH deprivation and access enhanced and prolonged
      relapse drinking and the expression of EtOH-seeking (318 +/- 22 responses), which
      was not observed in rats given equivalent consistent exposure to EtOH (66 +/- 11
      responses). CONCLUSIONS: Overall, the data indicated that the PSR model has
      ecological validity; factors that enhance EtOH craving in humans enhance the
      expression of EtOH-seeking in the PSR test. The data also detail factors that
      need to be examined to determine the biological basis of EtOH-seeking (e.g.,
      neuroadaptations that occur during the incubation period and following repeated
      cycles of EtOH drinking and abstinence).

PMID- 27696524
TI  - Erratum.

PMID- 27696525
TI  - Melatonin alleviates postinfarction cardiac remodeling and dysfunction by
      inhibiting Mst1.
AB  - Melatonin reportedly protects against several cardiovascular diseases including
      ischemia/reperfusion (I/R), atherosclerosis, and hypertension. The present study
      investigated the effects and mechanisms of melatonin on cardiomyocyte autophagy,
      apoptosis, and mitochondrial injury in the context of myocardial infarction (MI).
      We demonstrated that melatonin significantly alleviated cardiac dysfunction after
      MI. Four weeks after MI, echocardiography and Masson staining indicated that
      melatonin notably mitigated adverse left ventricle remodeling. The mechanism may
      be associated with increased autophagy, reduced apoptosis, and alleviated
      mitochondrial dysfunction. Furthermore, melatonin significantly inhibited Mst1
      phosphorylation while promoting Sirt1 expression after MI, which indicates that
      Mst1/Sirt1 signaling may serve as the downstream target of melatonin. We thus
      constructed a MI model using Mst1 transgenic (Mst1 Tg) and Mst1 knockout (Mst1-/-
      ) mice. The absence of Mst1 abolished the favorable effects of melatonin on
      cardiac injury after MI. Consistently, melatonin administration did not further
      increase autophagy, decrease apoptosis, or alleviate mitochondrial integrity and
      biogenesis in Mst1 knockout mice subjected to MI injury. These results suggest
      that melatonin alleviates postinfarction cardiac remodeling and dysfunction by
      upregulating autophagy, decreasing apoptosis, and modulating mitochondrial
      integrity and biogenesis. The attributed mechanism involved, at least in part,
      Mst1/Sirt1 signaling.

PMID- 27696526
TI  - Body composition in pituitary, adrenal and iatrogenic Cushing's syndrome and
      effects of DHEAS levels.

PMID- 27696528
TI  - Clinical and dermoscopic clues to differentiate pigmented nail bands: an
      International Dermoscopy Society study.
AB  - BACKGROUND: Longitudinal melanonychia might be difficult to differentiate and the
      use of dermoscopy can be useful for the preoperative evaluation and management
      decision. OBJECTIVES: The aim of our study was to investigate clinical and
      dermoscopic criteria of acquired longitudinal melanonychia in adults to identify
      the best predictors of melanoma using a multivariate analysis and to explore
      eventual new dermoscopic criteria for nail melanoma diagnosis. METHODS: In this
      retrospective observational study, 82 histopathologically diagnosed, acquired
      nail pigmented bands were collected and examined. All variables were included in
      the analysis and examined as possible predictors of nail melanoma. Both
      univariate and multivariable analyses have been performed. RESULTS: Among 82
      cases, 25 were diagnosed as nail melanoma and 57 as benign lesions (including 32
      melanocytic nevi and 25 benign melanocytic hyperplasia). Melanoma cases were
      significantly associated with a width of the pigmented band higher than 2/3 of
      the nail plate, grey and black colours, irregularly pigmented lines, Hutchinson
      and micro-Hutchinson signs, and nail dystrophy. Granular pigmentation, a newly
      defined dermoscopic criterion, was found in 40% of melanomas and only in 3.51% of
      benign lesions. CONCLUSIONS: Dermoscopic examination of longitudinal melanonychia
      provides useful information that could help clinicians to improve melanoma
      recognition.

PMID- 27696529
TI  - Outdoor cultivation of Dunaliella salina KU 11 using brine and saline lake water
      with raceway ponds in northeastern Thailand.
AB  - To evaluate the potential of algal biotechnology to replace traditional
      agriculture in northeastern Thailand, an open raceway cultivation system was
      developed to produce biomass and beta-carotene. Dunaliella salina KU 11 isolated
      from local saline soil was cultured in open raceway tanks using brine and saline
      lake water. Grown in modified Johnson's medium (with 2-3.5 M NaCl), the algae
      reached a maximum cell density on the fourth day (1.8 * 106 cells mL-1 ).
      Increasing KNO3 and NaHCO3 from 0.5 and 0.043 g L-1 to 1 and 2.1 g L-1 ,
      respectively, significantly improved the yields of biomass (0.33 g L-1 ) and beta
      carotene (19 mg L-1 ). Expected profits for algal production were evaluated, and
      it was found that this strain was suitable for outdoor cultivation and the
      developing algal industry in northeastern Thailand could produce high economic
      benefits (at least $64,120 per year per 0.16 ha).

PMID- 27696527
TI  - Differential Kv1.3, KCa3.1, and Kir2.1 expression in "classically" and
      "alternatively" activated microglia.
AB  - Microglia are highly plastic cells that can assume different phenotypes in
      response to microenvironmental signals. Lipopolysaccharide (LPS) and interferon
      gamma (IFN-gamma) promote differentiation into classically activated M1-like
      microglia, which produce high levels of pro-inflammatory cytokines and nitric
      oxide and are thought to contribute to neurological damage in ischemic stroke and
      Alzheimer's disease. IL-4 in contrast induces a phenotype associated with anti
      inflammatory effects and tissue repair. We here investigated whether these
      microglia subsets vary in their K+ channel expression by differentiating neonatal
      mouse microglia into M(LPS) and M(IL-4) microglia and studying their K+ channel
      expression by whole-cell patch-clamp, quantitative PCR and immunohistochemistry.
      We identified three major types of K+ channels based on their biophysical and
      pharmacological fingerprints: a use-dependent, outwardly rectifying current
      sensitive to the KV 1.3 blockers PAP-1 and ShK-186, an inwardly rectifying Ba2+ 
      sensitive Kir 2.1 current, and a Ca2+ -activated, TRAM-34-sensitive KCa 3.1
      current. Both KV 1.3 and KCa 3.1 blockers inhibited pro-inflammatory cytokine
      production and iNOS and COX2 expression demonstrating that KV 1.3 and KCa 3.1
      play important roles in microglia activation. Following differentiation with LPS
      or a combination of LPS and IFN-gamma microglia exhibited high KV 1.3 current
      densities (~50 pA/pF at 40 mV) and virtually no KCa 3.1 and Kir currents, while
      microglia differentiated with IL-4 exhibited large Kir 2.1 currents (~ 10 pA/pF
      at -120 mV). KCa 3.1 currents were generally low but moderately increased
      following stimulation with IFN-gamma or ATP (~10 pS/pF). This differential K+
      channel expression pattern suggests that KV 1.3 and KCa 3.1 inhibitors could be
      used to inhibit detrimental neuroinflammatory microglia functions. GLIA
      2016;65:106-121.

PMID- 27696523
TI  - Alcohol Use and Human Immunodeficiency Virus (HIV) Infection: Current Knowledge,
      Implications, and Future Directions.
AB  - Alcohol use is common among people living with human immunodeficiency virus
      (HIV). In this narrative review, we describe literature regarding alcohol's
      impact on transmission, care, coinfections, and comorbidities that are common
      among people living with HIV (PLWH), as well as literature regarding
      interventions to address alcohol use and its influences among PLWH. This
      narrative review identifies alcohol use as a risk factor for HIV transmission, as
      well as a factor impacting the clinical manifestations and management of HIV.
      Alcohol use appears to have additive and potentially synergistic effects on
      common HIV-related comorbidities. We find that interventions to modify drinking
      and improve HIV-related risks and outcomes have had limited success to date, and
      we recommend research in several areas. Consistent with Office of AIDS
      Research/National Institutes of Health priorities, we suggest research to better
      understand how and at what levels alcohol influences comorbid conditions among
      PLWH, to elucidate the mechanisms by which alcohol use is impacting
      comorbidities, and to understand whether decreases in alcohol use improve HIV
      relevant outcomes. This should include studies regarding whether state-of-the-art
      medications used to treat common coinfections are safe for PLWH who drink
      alcohol. We recommend that future research among PLWH include validated self
      report measures of alcohol use and/or biological measurements, ideally both.
      Additionally, subgroup variation in associations should be identified to ensure
      that the risks of particularly vulnerable populations are understood. This body
      of research should serve as a foundation for a next generation of intervention
      studies to address alcohol use from transmission to treatment of HIV.
      Intervention studies should inform implementation efforts to improve provision of
      alcohol-related interventions and treatments for PLWH in healthcare settings. By
      making further progress on understanding how alcohol use affects PLWH in the era
      of HIV as a chronic condition, this research should inform how we can mitigate
      transmission, achieve viral suppression, and avoid exacerbating common
      comorbidities of HIV and alcohol use and make progress toward the 90-90-90 goals
      for engagement in the HIV treatment cascade.

PMID- 27696532
TI  - Uptake of parasite-derived vesicles by astrocytes and microglial phagocytosis of
      infected erythrocytes may drive neuroinflammation in cerebral malaria.
AB  - Astrocytes and microglia are activated during cerebral malaria (CM) and
      contribute to the production and release of several mediators during
      neuroinflammatory processes. Whether these changes are the consequence of a
      direct crosstalk between glial cells and the malarial parasite and how these
      cells participate in the pathogenesis of CM is not yet clear. We therefore
      examined the interaction of astrocytes and microglia with Plasmodium berghei ANKA
      infected red blood cells using primary cell cultures derived from newborn C57BL/6
      mice. We observed a dynamic transfer of vesicles from the parasite to astrocytes
      within minutes of contact, and the phagocytosis of infected red blood cells by
      microglia. Differential gene expression studies using the Affymetrix GeneChip(r)
      microarray, and quantitative PCR analyses showed the increase in expression of
      the set of genes belonging to the immune response network in parasite activated
      astrocytes and microglia. Interestingly, expression of these genes was also
      significantly upregulated in brains of mice dying from CM compared with
      uninfected mice or infected mice that did not develop the neuropathology.
      Accumulation of parasite-derived vesicles within astrocytes, and the phagocytosis
      of infected red blood cells by microglia induced a subsequent increase in
      interferon gamma inducible protein 10 (IP10) in both the brain and plasma of
      infected mice at the onset of CM, confirming a role for this molecule in CM
      pathogenesis. Altogether, these observations point to a possible role for glial
      cells in the neuropathological processes leading to CM. GLIA 2016 GLIA 2017;65:75
      92.

PMID- 27696530
TI  - Stimulation-induced transient changes in neuronal activity, blood flow and N
      acetylaspartate content in rat prefrontal cortex: a chemogenetic fMRS-BOLD study.
AB  - Brain activation studies in humans have shown the dynamic nature of neuronal N
      acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) based on changes in
      their MRS signals in response to stimulation. These studies demonstrated that
      upon visual stimulation there was a focal increase in cerebral blood flow (CBF)
      and a decrease in NAA or in the total of NAA and NAAG signals in the visual
      cortex, and that these changes were reversed upon cessation of stimulation. In
      the present study we have developed an animal model in order to explore the
      relationships between brain stimulation, neuronal activity, CBF and NAA. We use
      "designer receptor exclusively activated by designer drugs" (DREADDs) technology
      for site-specific neural activation, a local field potential electrophysiological
      method for measurement of changes in the rate of neuronal activity, functional
      MRS for measurement of changes in NAA and a blood oxygenation level-dependent
      (BOLD) MR technique for evaluating changes in CBF. We show that stimulation of
      the rat prefrontal cortex using DREADDs results in the following: (i) an increase
      in level of neuronal activity; (ii) an increase in BOLD and (iii) a decrease in
      the NAA signal. These findings show for the first time the tightly coupled
      relationships between stimulation, neuron activity, CBF and NAA dynamics in
      brain, and also provide the first demonstration of the novel inverse stimulation
      NAA phenomenon in an animal model.

PMID- 27696531
TI  - Effect of narrow band ultraviolet B phototherapy as monotherapy or combination
      therapy for vitiligo: a meta-analysis.
AB  - BACKGROUND: The treatment of vitiligo is still one of the most difficult
      dermatological challenges, although there are many therapeutic options. Narrow
      band ultraviolet B (NB-UVB) phototherapy is considered to be a very important
      modality for generalized vitiligo. OBJECTIVE: The aim of this study was to
      explore whether a combination of NB-UVB and topical agents would be superior to
      NB-UVB alone for treating vitiligo. METHODS: We searched the electronic databases
      such as PUBMED, EMBASE, Cochrane Library, and Web of Science. The primary outcome
      was the proportion of >=50% repigmentation (a clinical significance), and
      secondary outcome was the proportion of >=75% repigmentation (an excellent
      response). RESULTS: Seven randomized controlled trials (RCTs) involving 240
      patients (413 lesions) were included in this meta-analysis. The study showed no
      significant difference between NB-UVB combination therapy (NB-UVB and topical
      calcineurin inhibitor or vitamin D analogs) and NB-UVB monotherapy in the
      outcomes of >=50% repigmentation and >=75% repigmentation. However, lesions
      located on the face and neck had better results in >=50% repigmentation (RR =
      1.40, 95% CI 1.08-1.81) and >=75% repigmentation (RR = 1.88, 95% CI 1.10-3.20)
      with NB-UVB and topical calcineurin inhibitor combination therapy vs. NB-UVB
      monotherapy. CONCLUSIONS: The meta-analysis suggested that adding neither topical
      calcineurin inhibitors nor topical vitamin-D3 analogs on NB-UVB can yield
      significantly superior outcomes than NB-UVB monotherapy for treatment of
      vitiligo. However, addition of topical calcineurin inhibitors to NB-UVB may
      increase treatment outcomes in vitiligo affecting face and neck.

PMID- 27696534
TI  - Esterase EstK from Pseudomonas putida mt-2: An enantioselective acetylesterase
      with activity for deacetylation of xylan and poly(vinylacetate).
AB  - An extracellular esterase gene estK was identified in Pseudomonas putida mt-2 and
      overexpressed at high levels in Escherichia coli. The recombinant EstK enzyme was
      purified and characterized kinetically against p-nitrophenyl ester and other aryl
      alkyl ester substrates and found to be selective for hydrolysis of acetyl ester
      substrates with high activity for p-nitrophenyl acetate (kcat 5.5 Sec-1 , KM 285
      uM). Recombinant EstK was found to catalyze deacetylation of acetylated beech
      xylan, indicating a possible in vivo function for this enzyme, and partial
      deacetylation of a synthetic polymer (poly(vinylacetate)). EstK was found to
      catalyze enantioselective hydrolysis of racemic 1-phenylethyl acetate, generating
      1R-phenylethanol with an enantiomeric excess of 80.4%.

PMID- 27696533
TI  - Low startle magnitude may be a behavioral marker of vulnerability to cocaine
      addiction.
AB  - Cocaine addicted men have low startle magnitude persisting during prolonged
      abstinence. Low startle rats show greater cocaine self-administration than high
      startle rats. Low startle may be a marker of a vulnerability to heightened
      cocaine-related behaviors in rats and similarly may be a marker of vulnerability
      to cocaine addiction in humans.

PMID- 27696535
TI  - Community Unemployment and Disaster-Related Stressors Shape Risk for
      Posttraumatic Stress in the Longer-Term Aftermath of Hurricane Sandy.
AB  - Persons living in communities with limited resources are at heightened risk of
      posttraumatic stress (PTS) after disasters, especially if they were highly
      exposed. The support deterrence desistence model and the conservation of
      resources theory suggest that this risk might increase in the longer-term
      aftermath of disasters. In the present study, we aimed to test this hypothesis.
      Two population-based samples of New York City residents in communities affected
      by Hurricane Sandy were surveyed at either 13-16 months (Time 1; n = 421) or 25
      28 months (Time 2; n = 420) postdisaster. Participants reported on their exposure
      to disaster-related stressors and PTS. The percentage of residents who were
      unemployed in participants' census tracts was collected from the 2008-2012
      American Community Survey. Multilevel models found that disaster-related
      stressors were more strongly associated with PTS for participants living in
      communities with high unemployment, but only at Time 2 (Est. = .58, SE = .21, p =
      .006). Mapping of community unemployment and disaster-related stressors suggested
      that communities in southern Brooklyn and Queens, and northeastern Staten Island
      were at particularly high risk for PTS at Time 2. The results suggest the need
      for ongoing support to economically disadvantaged communities in which residents
      have endured disaster-related stressors.

PMID- 27696536
TI  - The putative Walker A and Walker B motifs of Rrp2 are required for the growth of
      Borrelia burgdorferi.
AB  - Rrp2 encodes a putative bacterial enhancer binding protein (bEBP) in Borrelia
      burgdorferi. Point mutation (G239C) of Rrp2 abolishes the transcriptional
      activation of sigma54 -dependent rpoS. In contrast to canonical bEBPs that are
      dispensable for bacterial growth, Rrp2 is essential for borrelial growth in BSK
      medium. It has been believed that Rrp2's ATPase activity is not required for cell
      growth, but experimental evidence supporting this notion has been lacking. In
      particular, it has remained unclear whether the residue G239 is involved in
      Rrp2's presumptive ATPase activity. To address these information gaps, we
      examined the roles of Rrp2's potential strategic signatures including the G239
      residue and the putative Walker A and Walker B motifs. Herein it was showed that
      Rrp2 has ATP binding and hydrolysis activities engendered by the Walker A and B
      motifs respectively. However, these activities were not significantly impaired by
      a G239C mutation. Further mutagenesis analyses indicated that Rrp2's Walker A and
      B motifs are required for borrelial growth; mutations of key residues in these
      two motifs were lethal to B. burgdorferi. The combined data suggest that the
      Walker A and Walker B motifs of Rrp2 are involved in the control of another
      unknown RpoS-independent gene product(s) associated with borrelial replication.

PMID- 27696537
TI  - Expression, modulation, and clinical correlates of the autophagy protein Beclin-1
      in esophageal adenocarcinoma.
AB  - Esophageal adenocarcinoma (EAC) is characterized by rapidly increasing incidence
      and mortality rates and poor survival. Efficacious preventive and treatment
      options are urgently needed. An increasing number of pharmacologic agents
      targeting cancer cell death via autophagy mechanisms are being evaluated in hopes
      of circumventing apoptotic and therapeutic resistance. We report for the first
      time, loss of Beclin-1, a key mediator of autophagy, was significantly linked to
      prognostic factors in EAC. Specifically, Beclin-1 expression loss occurred in
      49.0% of EAC patients versus 4.8% of controls. There was a significant inverse
      correlation between loss of Beclin-1 with histologic grade and tumor stage
      supporting a tumor suppressive role for Beclin-1. Autophagy modulation linked to
      cell death was examined in EAC cell lines following treatment with a
      proanthocyanidin-rich cranberry extract, C-PAC, and the commonly used autophagy
      inducer, rapamycin. C-PAC induced Beclin-1-independent autophagy in EAC cells
      characterized by reduced phosphorylation at serine 15 and 93, and significant
      cell death induction. In contrast, rapamycin-induced autophagy resulted in
      concomitant, increases in total Beclin-1 levels as well as Beclin-1
      phosphorylation in a cell line specific manner, leading to long-term cell
      survival. Furthermore, autophagic LC3-II was induced by C-PAC following siRNA
      suppression of Beclin-1 in EAC cells. Together these data support a prognostic
      role of Beclin-1 in EAC with evidence that Beclin-dependent autophagy induction
      is agent specific. Future studies are necessary to fully interrogate the role
      autophagy plays in the progression of normal tissue to EAC and how specific
      agents targeting autophagic mechanisms can be efficaciously applied for cancer
      prevention or treatment. (c) 2015 Wiley Periodicals, Inc.

PMID- 27696538
TI  - Black raspberries demethylate Sfrp4, a WNT pathway antagonist, in rat esophageal
      squamous cell papilloma.
AB  - Aberrant methylation of DNA is a common event in the development of cancers,
      including squamous cell carcinoma (SCC) of the human esophagus. In the present
      study, we determined: (a) whether aberrant DNA methylation also occurs in the
      development of N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat
      esophagus, a model of human esophageal SCC; and (b) if so, whether dietary black
      raspberries (BRBs) are capable of preventing this aberrant DNA methylation. A
      diet containing 5% BRBs inhibited the development of NMBA-induced tumors in the
      rat esophagus. This inhibition was associated with reduced mRNA levels of the DNA
      methyltransferases, Dnmt1 and Dnmt3b, in both dysplastic lesions and in
      papillomas of the esophagus. In addition, promoter methylation of Sfrp4, a WNT
      pathway antagonist, was significantly reduced by the berry diet, and this was
      associated with decreased nuclear localization of beta-CATENIN and reduced
      expression of c-MYC protein in NMBA-treated esophagi. Decreased promoter
      methylation of Sfrp4 correlated with decreased expression of Dmnt3b and,
      ultimately, with increased Sfrp4 mRNA expression. This suggests that epigenetic
      alterations in NMBA-induced rat esophageal tumorigenesis recapitulate epigenetic
      events in human esophageal SCC, and that BRBs could be useful in preventing the
      aberrant DNA methylation involved in the development of human esophageal SCC. (c)
      2015 Wiley Periodicals, Inc.

PMID- 27696540
TI  - Humanistic and economic outcomes of pharmacist-provided medication review in the
      community-dwelling elderly: A systematic review and meta-analysis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Recent reviews have shown that pharmacist-provided
      medication review in the elderly can improve clinical outcomes and reduce
      medication discrepancies compared with usual care. However, none determined
      whether these translate to improved humanistic and economic outcomes. This review
      sought to evaluate the effects of medication review on health-related quality of
      life (HRQoL) and healthcare costs in the elderly. METHODS: A systematic search of
      MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane library for studies
      published in English from inception to 31 August 2015 was conducted. The review
      included studies lasting at least 3 months that randomly assigned community
      dwelling participants aged at least 65 years to receive either pharmacist
      provided medication review or usual care. Studies set in nursing homes were
      excluded. RESULTS AND DISCUSSION: The review identified 25 studies that included
      15 341 participants and lasted between 3 and 36 months. Twenty and 13 studies
      reported HRQoL and economic outcomes, respectively. Overall, there was no
      significant difference in HRQoL and healthcare costs between pharmacist-provided
      medication review and usual care. Meta-analysis of studies that reported the 36
      item Short-Form Health Survey found significant differences in favour of usual
      care in the body pain (mean difference: 2.94, 95% CI: 0.54-5.34, P = 0.02) and
      general health perception (mean difference: 1.83, 95% CI: 0.16-3.50, P = 0.03)
      domains, whereas there were no significant differences in other domains. Meta
      analysis of the EuroQol-5D utility (mean difference: -0.01, 95% CI: -0.02-0.01, P
      = 0.57) and visual analogue scale (mean difference: 0.01, 95% CI: -3.24-3.26, P =
      1.00) found no significant differences. Costs of hospitalization, medication and
      other healthcare resources consumed were similar between groups. WHAT IS NEW AND
      CONCLUSION: Humanistic and economic outcomes of pharmacist-provided medication
      review were largely similar to those of usual care. Further research using more
      robust methodology is needed to determine whether improved medication management
      can improve HRQoL and reduce healthcare costs. Careful thought should be given to
      capturing relevant outcomes that reflect the potential benefits of this
      intervention.

PMID- 27696539
TI  - Interlaboratory validation of organism recovery for use in 42-day sediment
      toxicity tests with Hyalella azteca.
AB  - Environment and Climate Change Canada has developed a 42-d sediment toxicity test
      that includes a reproduction endpoint with the freshwater amphipod Hyalella
      azteca. The new methodology conducts the entire exposure in sediment, in contrast
      to existing standardized methods whereby adults are transferred to a water-only
      exposure before release of their first brood at day 28. This midtest transfer to
      clean water was because of the results of a juvenile H. azteca recovery trial
      conducted in the 1990s concluding that reproductive endpoints could be biased
      because of low recovery of young amphipods from sediment. Using a new procedure
      and reduced volume of sediment, an interlaboratory recovery trial was conducted
      using 2-d to 5-d old H. azteca added to control sediment. A total of 29
      technicians from 8 laboratories participated in the present study. The average
      recovery for all laboratories and all technicians was 76% (coefficient of
      variation [CV] = 30%). Based on an initial target recovery of at least 80%, 19 of
      29 (66%) technicians met this criterion, with an average recovery for this group
      of 88% (CV = 8.3%). Factors that reduced recovery success included: not using a
      light table, technicians with minimal sediment testing experience, and the use of
      imported young amphipods with limited acclimation. Excluding those results, the
      overall average recovery, which included 17 participating technicians, increased
      from 76% to 88% and lowered the CV from 30% to 8.6%. Based on these results,
      Environment and Climate Change Canada will recommend >=85% average recovery of
      young in control sediment and require >=80% as a technician performance criterion
      in its new test design for the reproduction methodology. Environ Toxicol Chem
      2017;36:1085-1089. (c) 2016 Crown in the right of Canada. Published by Wiley
      Periodicals Inc. on behalf of SETAC.

PMID- 27696541
TI  - Factors promoting resident deaths at aged care facilities in Japan: a review.
AB  - Due to an increasingly ageing population, the Japanese government has promoted
      elderly deaths in aged care facilities. However, existing facilities were not
      designed to provide resident end-of-life care and the proportion of aged care
      facility deaths is currently less than 10%. Consequently, the present review
      evaluated the factors that promote aged care facility resident deaths in Japan
      from individual- and facility-level perspectives to exploring factors associated
      with increased resident deaths. To achieve this, MEDLINE, CINAHL, Web of Science
      and Ichushi databases were searched on 23 January 2016. Influential factors were
      reviewed for two healthcare services (insourcing and outsourcing facilities) as
      well as external healthcare agencies operating outside facilities. Of the
      original 2324 studies retrieved, 42 were included in analysis. Of these studies,
      five focused on insourcing, two on outsourcing, seven on external agencies and
      observed facility/agency-level factors. The other 28 studies identified
      individual-level factors related to death in aged care facilities. The present
      review found that at both facility and individual levels, in-facility resident
      deaths were associated with healthcare service provision, confirmation of
      resident/family end-of-life care preference and staff education. Additionally,
      while outsourcing facilities did not require employment of physicians/nursing
      staff to accommodate resident death, these facilities required visits by
      physicians and nursing staff from external healthcare agencies as well as
      residents' healthcare input. This review also found few studies examining
      outsourcing facilities. The number of healthcare outsourcing facilities is
      rapidly increasing as a result of the Japanese government's new tax incentives.
      Consequently, there may be an increase in elderly deaths in outsourcing
      healthcare facilities. Accordingly, it is necessary to identify the factors
      associated with residents' deaths at outsourcing facilities.

PMID- 27696542
TI  - CSF cytology diagnosis of NRAS-mutated primary leptomeningeal melanomatosis with
      neurocutaneous melanosis.

PMID- 27696543
TI  - The effect of renal transplantation on quality of sleep in former dialysis
      patients.
AB  - Data on sleep quality in renal transplanted (RTX) patients are scarce, and
      longitudinal studies are lacking. The purpose of this study was to assess the
      prevalence of sleep complaints in RTX patients and identify variables associated
      with improvement in sleep quality. In a longitudinal study, 301 dialysis patients
      were followed for up to 5.5 years, during which time 142 were transplanted. Out
      of the transplanted patients, a total of 110 were eligible for inclusion. Sleep
      quality and depression were assessed with the validated questionnaires Pittsburgh
      Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI), and data were
      collected during dialysis and after RTX. Based on PSQI scores, 59% were
      characterized as poor sleepers after RTX compared to 75% when in dialysis (P =
      0.016). A total of 46% experienced a clinical relevant improvement in overall
      sleep quality, while 21% experienced a clinical relevant deterioration. In
      multivariable analyses, clinical meaningful change in sleep quality was not
      associated with either depressive symptoms assessed with BDI or other clinical
      variables. Sleep quality improved after RTX in nearly half of the patients, but
      poor sleep quality was prevalent in RTX patients. Therefore, sleep quality should
      routinely be assessed in RTX patients.

PMID- 27696544
TI  - The Learning Curve for Transcatheter Mitral Valve Repair With MitraClip.
AB  - OBJECTIVES: This study sought to assess the learning curve for TMVR for treatment
      of primary mitral regurgitation (MR). BACKGROUND: Data are lacking regarding the
      technical experience required to achieve optimal clinical outcomes with
      transcatheter mitral valve repair (TMVR) using the edge-to-edge MitraClip
      technique. METHODS: We examined the sequential experience of the first 75
      patients (age 80 +/- 9 years; 77% male) who underwent TMVR at our institution. A
      sequence number of each patient was assigned as a continuous variable and in
      tertiles for analysis. RESULTS: TMVR with MitraClip was successful in 97% with an
      average procedural time of 106 +/- 39 minutes. The 30-day rate of major adverse
      cardiovascular events was 7%. With increased case experience, there were
      decreases in procedural time, fluoroscopy time, length of hospital stay, and
      major adverse cardiovascular events. Procedural success, residual mitral
      regurgitation and NYHA functional classification at 30-day follow-up remained
      unchanged throughout the experience. CONCLUSIONS: The learning curve for TMVR
      with MitraClip for treatment of primary MR is characterized by a sequential
      reduction in procedure time, fluoroscopy time, procedural complications, and
      hospital length of stay at a tertiary academic medical center. Thirty-day
      procedural results are favorable and similar during the initial learning period.

PMID- 27696545
TI  - Drug-Coated Balloons: Seeking a Niche in the Treatment of Coronary Artery
      Disease.

PMID- 27696546
TI  - Response: Letter to the Editor and Response: Comparison of Cutting Balloon
      Angioplasty and Percutaneous Balloon Angioplasty of Arteriovenous Fistula
      Stenosis: A Meta-Analysis and Systematic Review of Randomized Clinical Trials.

PMID- 27696547
TI  - CORRIGENDUM.

PMID- 27696548
TI  - Spectroscopic exploration and thermodynamic characterization of desvenlafaxine
      interacting with fluorescent bovine serum albumin.
AB  - The mechanism of the interaction between bovine serum albumin (BSA) and
      desvenlafaxine was studied using fluorescence, ultraviolet absorption, 3
      dimensional fluorescence spectroscopy, circular dichroism, synchronous
      fluorescence spectroscopy, cyclic voltametry, differential scanning calorimetry,
      and attenuated total reflection-Fourier transform infrared spectroscopic
      techniques under physiological condition at pH 7.4. Stern-Volmer calculations
      authenticate the fluorescence of BSA that was quenched by desvenlafaxine in a
      collision quenching mode. The fluorescence quenching method was used to evaluate
      number of binding sites "n" and binding constant KA that were measured, and
      various thermodynamic parameters were evaluated at different temperatures by
      using the van't Hoff equation and differential scanning calorimetry technique,
      which indicated a spontaneous and hydrophobic interaction between BSA and
      desvenlafaxine. According to the Forster theory we calculate the distance between
      the donor, BSA and acceptor, desvenlafaxine molecules. Furthermore, circular
      dichroism and attenuated total reflection-Fourier transform infrared spectroscopy
      indicate nominal changes in the secondary structure of the protein.

PMID- 27696549
TI  - Using a choice experiment and birder preferences to guide bird-conservation
      funding.
AB  - Conservation of biodiversity, including birds, continues to challenge natural
      area managers. Stated-preference methods (e.g., choice experiment [CE]) are
      increasingly used to provide data for valuation of natural ecosystems. We used a
      CE to calculate birders' willingness to pay for different levels of bioecological
      attributes (threatened species, endemic species, and diversity) of birding sites
      with hypothetical entry fees. The CE was delivered at popular birding and
      avitourism sites in Australia and the United Kingdom. Latent-class modeling
      results revealed heterogeneous preferences among birders and correspondingly
      variable willingness to pay. Four clear groups were apparent: quantity-driven
      birders, special-birds seekers, confused respondents, and price-is-no-object
      birders. Quantity-driven birders were attracted to sites that deliver high levels
      of diversity and endemic species for which they were willing to pay $135 and $66
      to visit, respectively, above what they were willing to pay to visit a site with
      low levels of diversity and few endemic and threatened species . Special-bird
      seekers valued threatened species and high levels of endemic species most
      (willingness to pay $45 and $46, respectively). Confused respondents' preferences
      were difficult to determine, but they were the most sensitive to the hypothetical
      entry fees, unlike the price-is-no-object birders, who were not at all sensitive
      to cost. Our findings demonstrate that birders are amenable to paying for their
      preferred birding experience. These payments could provide an alternative source
      of funding in some avitourism sites on both public and private land. Such
      alternative revenue streams should be explored and given full consideration in
      increasingly competitive conservation-financing environments.

PMID- 27696550
TI  - Effect of a repeated tongue-lift motor task for tongue function.
AB  - This study investigated the effect of repeated tongue motor tasks on suprahyoid
      muscle activity and tongue pressure. Fourteen participants performed three series
      of a standardized tongue-lift training (TLT) task on each of five consecutive
      days. Electromyographic (EMG) activity from suprahyoid muscles and tongue
      pressure were recorded. In the first and third TLT series, participants were
      instructed only to target different force levels. During the second TLT series,
      visual feedback of the force level was given. One series consisted of three
      measurements [at 10%, 20%, and 40% of maximum voluntary contraction (MVC),
      respectively]. The coefficient of determination of the target force level-EMG
      curve and the target force level-tongue pressure curve was calculated from all
      series. There were no statistically significant day-to-day differences in EMG
      root mean square (RMS) values and tongue pressure during MVC. The coefficients of
      determination of tongue pressure in the first series on day 1 were statistically
      significantly lower than the coefficients of determination in the first series on
      day 5. These findings suggest that the control of tongue pressure improved, while
      the maximum force remained constant. These results could have implications for
      treatment paradigms related to learning for patients with compromised tongue
      function, such as swallowing disorders or dysphagia.

PMID- 27696551
TI  - Pethidine hydrochloride is a better sedation method for pharyngeal observation by
      transoral endoscopy compared with no sedation and midazolam.
AB  - BACKGROUND AND AIM: Standard surveillance methods for pharyngeal cancer have not
      been established. We conducted a randomized controlled trial to investigate the
      best sedation method for pharyngeal observation using transoral endoscopy.
      METHODS: In total, 120 patients who underwent surveillance or diagnostic
      examinations for esophageal cancer were enrolled and divided equally into three
      groups (no sedation, midazolam, or pethidine hydrochloride). In the midazolam
      group, midazolam was given i.v. maintaining a Ramsay score of 3. In the pethidine
      group, pethidine hydrochloride (35 mg) given i.v. Seven sites in five pharyngeal
      regions were observed on insertion of the endoscope, and graded (0 = poor, 1 =
      good). After examination, the five pharyngeal regions were scored using a seven
      point scale. Primary endpoint was the total score from the five pharyngeal
      regions. Secondary endpoints were the proportion of the perfect score using the
      seven-point scale, discomfort score, and adverse events. RESULTS: Mean total
      scores for the no sedation group, the midazolam group and the pethidine group
      were 5.7, 5.5, and 6.8, respectively (P < 0.0001). Proportion of patients with a
      perfect score for the no sedation group, the midazolam group and the pethidine
      group were 53%, 35%, and 89%, respectively (P < 0.0001). The pethidine group had
      better results than the other two groups. Discomfort score and adverse events
      were low in the pethidine group. CONCLUSION: Pethidine hydrochloride is a
      feasible and safe sedation method, and was superior to no sedation and midazolam
      regarding pharyngeal observation of esophageal cancer patients.

PMID- 27696552
TI  - Remembering Heinrich Malling.

PMID- 27696553
TI  - Developmental regulation and modulation of apoptotic genes expression in sheep
      oocytes and embryos cultured in vitro with L-carnitine.
AB  - The objective of this study was to find out the impact of L-carnitine (10 mM) on
      developmental regulation of preimplantation sheep embryos cultured in vitro when
      supplemented in maturation medium and post-fertilization medium separately.
      Subsequent objective was to observe the L-carnitine-mediated alteration in
      expression of apoptotic genes (Bcl2, Bax, Casp3 and PCNA) in sheep oocytes and
      developing embryos produced in vitro. Oocytes matured with L-carnitine showed
      significantly (p < .05) higher cleavage (67.23% vs 43.12%), morula (47.65% vs
      28.58%) and blastocysts (32.12% vs 13.24%) percentage as compared to presumptive
      zygotes cultured with L-carnitine during post-fertilization period. So it is
      suggested to use L-carnitine during maturation than post-fertilization period.
      Antiapoptotic and proliferative effects of L-carnitine were confirmed by inducing
      culture medium with actinomycin D (apoptotic agent) and TNFalpha
      (antiproliferative agent), respectively, with and without L-carnitine. Oocytes
      and embryos cultured with actinomycin D and TNFalpha showed developmental arrest
      with significant (p < .05) decrease in morula and blastocysts percentage but
      supplementation of L-carnitine to actinomycin D and TNFalpha induced culture
      medium showed similar result as that of control. L-carnitine supplementation
      during IVM significantly (p < .05) upregulated the expression of Bcl2 and PCNA
      genes in majority of the developmental stages. Although L-carnitine upregulated
      the expression of Bax in initial developmental stages but downregulated at latter
      part, whereas the expression of Casp3 was upregulated upto 16-cell stage but
      after that there was no difference in expression. Expression of GAPDH gene was
      not affected by L-carnitine supplementation. In conclusion, L-carnitine acted as
      an antiapoptotic and proliferative compound during embryo development and
      supplementation of L-carnitine during IVM altered the expression of apoptotic
      genes in the developmental stages of embryos.

PMID- 27696554
TI  - Evaluation of Staphylococcus aureus DNA aptamer by enzyme-linked aptamer assay
      and isothermal titration calorimetry.
AB  - To monitor the specificity of Staphylococcus aureus aptamer (SA-31) against its
      target cell, we used enzyme-linked aptamer assay. In the presence of target cell,
      horseradish peroxidase-conjugated streptavidin bound to biotin-labeled SA-31
      showed specific binding to S  aureus among 3 different bacteria with limit of
      detection of 103 colony-forming unit per milliliter. The apparent Ka was 1.39 MUM
      1  +/- 0.3 MUM-1 . The binding of SA-31 to membrane proteins extracted from cell
      surface was characterized using isothermal titration calorimetry, and the effect
      of changes in binding temperature and salt concentrations of binding buffer was
      evaluated based on thermodynamic parameters (Ka , DeltaH, and DeltaG). Since
      binding of aptamer to its targets solely depends on its 3-dimensional structure
      under experimental conditions used in selection process, the change in
      temperature and ion concentration changed the affinity of SA-31 to its target on
      surface of bacteria. At 4 degrees C, SA-31 did not show an affinity to its target
      with poor heat change upon injection of membrane fraction to aptamer solution.
      However, the apparent association constants of SA-31 slightly varied from Ka  =
      1.56 MUM-1  +/- 0.69 MUM-1 at 25 degrees C to Ka  = 1.03 MUM-1  +/- 0.9 MUM-1 at
      37 degrees C. At spontaneously occurring exothermic binding reactions, affinities
      of S aureus aptamer to its target were also 9.44 MUM-1  +/- 0.38 MUM-1 at 50mM,
      1.60 MUM-1  +/- 0.11 MUM-1 at 137mM, and 3.28 MUM-1  +/- 0.46 MUM-1 at 200 mM of
      salt concentration. In this study, it was demonstrated that enzyme-linked aptamer
      assay and isothermal titration calorimetry were useful tools for studying the
      fundamental binding mechanism between a DNA aptamer and its target on the outer
      surface of S aureus.

PMID- 27696555
TI  - Relationship between mechanical properties and bond durability of short fiber
      reinforced resin composite with universal adhesive.
AB  - The purpose of this study was to determine the relationship between mechanical
      properties and bond durability of short fiber-reinforced resin composite with
      universal adhesive. As controls, micro-hybrid and nano-hybrid resin composites
      were tested. The universal adhesives used were Scotchbond Universal, Adhese
      Universal, and G-Premio Bond. The fracture toughness and flexural properties of
      resin composites, and shear bond strength and shear fatigue strength of universal
      adhesive with resin composite using both total-etch and self-etch modes were
      determined. In the results, short fiber-reinforced resin composite showed
      significantly higher fracture toughness than did micro-hybrid and nano-hybrid
      resin composites. The flexural strength and modulus of short fiber-reinforced and
      nano-hybrid resin composites were significantly lower than were those of micro
      hybrid resin composites. Regardless of etching mode, the shear bond strength of
      universal adhesives with short fiber-reinforced resin composite did not show any
      significant differences from micro-hybrid and nano-hybrid resin composites. The
      shear fatigue strength of universal adhesives with short fiber-reinforced resin
      composite and micro-hybrid resin composites were significantly higher than that
      of nano-hybrid resin composites. The results of this study suggest that the
      mechanical properties of short fiber-reinforced resin composite improve their
      bond durability with universal adhesive.

PMID- 27696557
TI  - Changing epidemiology of oral squamous cell carcinoma of the tongue: A global
      study.
AB  - BACKGROUND: There are reports about the changing epidemiology of tongue squamous
      cell carcinoma (SCC), with recent reports indicating an increasing incidence in
      young women. METHODS: Data on incident cases of tongue SCC were collected from
      cancer registries worldwide. RESULTS: Data from a total of 22 cancer registries
      and 89,212 incident cases of tongue SCC worldwide were included. Most areas
      experienced an incidence increase ranging from 0.4% to 3.3% per year. There was a
      significant difference in the incidence increase between sexes in 11 of the 22
      registries. In 14 of the 22 registries studied, the increase in incidence of
      tongue SCC was higher in the group of subjects <45 years old than those >=45
      years old. CONCLUSION: This study suggests a general but not universal increase
      in the incidence of tongue SCC worldwide. In some regions of the world, we
      observed a shifting trend toward women and/or younger patients. (c) 2016 Wiley
      Periodicals, Inc. Head Neck 39: 297-304, 2017.

PMID- 27696559
TI  - Toward reassessing data-deficient species.
AB  - One in 6 species (13,465 species) on the International Union for Conservation of
      Nature (IUCN) Red List is classified as data deficient due to lack of information
      on their taxonomy, population status, or impact of threats. Despite the chance
      that many are at high risk of extinction, data-deficient species are typically
      excluded from global and local conservation priorities, as well as funding
      schemes. The number of data-deficient species will greatly increase as the IUCN
      Red List becomes more inclusive of poorly known and speciose groups. A strategic
      approach is urgently needed to enhance the conservation value of data-deficient
      assessments. To develop this, we reviewed 2879 data-deficient assessments in 6
      animal groups and identified 8 main justifications for assigning data-deficient
      status (type series, few records, old records, uncertain provenance, uncertain
      population status or distribution, uncertain threats, taxonomic uncertainty, and
      new species). Assigning a consistent set of justification tags (i.e., consistent
      assignment to assessment justifications) to species classified as data deficient
      is a simple way to achieve more strategic assessments. Such tags would clarify
      the causes of data deficiency; facilitate the prediction of extinction risk;
      facilitate comparisons of data deficiency among taxonomic groups; and help
      prioritize species for reassessment. With renewed efforts, it could be
      straightforward to prevent thousands of data-deficient species slipping unnoticed
      toward extinction.

PMID- 27696558
TI  - Fast diffusion kurtosis imaging (DKI) with Inherent COrrelation-based
      Normalization (ICON) enhances automatic segmentation of heterogeneous diffusion
      MRI lesion in acute stroke.
AB  - Diffusion kurtosis imaging (DKI) has been shown to augment diffusion-weighted
      imaging (DWI) for the definition of irreversible ischemic injury. However, the
      complexity of cerebral structure/composition makes the kurtosis map
      heterogeneous, limiting the specificity of kurtosis hyperintensity to acute
      ischemia. We propose an Inherent COrrelation-based Normalization (ICON) analysis
      to suppress the intrinsic kurtosis heterogeneity for improved characterization of
      heterogeneous ischemic tissue injury. Fast DKI and relaxation measurements were
      performed on normal (n = 10) and stroke rats following middle cerebral artery
      occlusion (MCAO) (n = 20). We evaluated the correlations between mean kurtosis
      (MK), mean diffusivity (MD) and fractional anisotropy (FA) derived from the fast
      DKI sequence and relaxation rates R1 and R2 , and found a highly significant
      correlation between MK and R1 (p < 0.001). We showed that ICON analysis
      suppressed the intrinsic kurtosis heterogeneity in normal cerebral tissue,
      enabling automated tissue segmentation in an animal stroke model. We found
      significantly different kurtosis and diffusivity lesion volumes: 147 +/- 59 and
      180 +/- 66 mm3 , respectively (p = 0.003, paired t-test). The ratio of kurtosis
      to diffusivity lesion volume was 84% +/- 19% (p < 0.001, one-sample t-test). We
      found that relaxation-normalized MK (RNMK), but not MD, values were significantly
      different between kurtosis and diffusivity lesions (p < 0.001, analysis of
      variance). Our study showed that fast DKI with ICON analysis provides a promising
      means of demarcation of heterogeneous DWI stroke lesions.

PMID- 27696560
TI  - Functional characterization of UDP-rhamnose-dependent rhamnosyltransferase
      involved in anthocyanin modification, a key enzyme determining blue coloration in
      Lobelia erinus.
AB  - Because structural modifications of flavonoids are closely related to their
      properties, such as stability, solubility, flavor and coloration, characterizing
      the enzymes that catalyze the modification reactions can be useful for
      engineering agriculturally beneficial traits of flavonoids. In this work, we
      examined the enzymes involved in the modification pathway of highly glycosylated
      and acylated anthocyanins that accumulate in Lobelia erinus. Cultivar Aqua Blue
      (AB) of L. erinus is blue-flowered and accumulates delphinidin 3-O-p
      coumaroylrutinoside-5-O-malonylglucoside-3'5'-O-dihydroxycinnamoylglucoside
      (lobelinins) in its petals. Cultivar Aqua Lavender (AL) is mauve-flowered, and LC
      MS analyses showed that AL accumulated delphinidin 3-O-glucoside (Dp3G), which
      was not further modified toward lobelinins. A crude protein assay showed that
      modification processes of lobelinin were carried out in a specific order, and
      there was no difference between AB and AL in modification reactions after
      rhamnosylation of Dp3G, indicating that the lack of highly modified anthocyanins
      in AL resulted from a single mutation of rhamnosyltransferase catalyzing the
      rhamnosylation of Dp3G. We cloned rhamnosyltransferase genes (RTs) from AB and
      confirmed their UDP-rhamnose-dependent rhamnosyltransferase activities on Dp3G
      using recombinant proteins. In contrast, the RT gene in AL had a 5-bp nucleotide
      deletion, resulting in a truncated polypeptide without the plant secondary
      product glycosyltransferase box. In a complementation test, AL that was
      transformed with the RT gene from AB produced blue flowers. These results suggest
      that rhamnosylation is an essential process for lobelinin synthesis, and thus the
      expression of RT has a great impact on the flower color and is necessary for the
      blue color of Lobelia flowers.

PMID- 27696561
TI  - Evaluation of the Relationship Between Microalbuminuria and Urine Ischemia
      Modified Albumin Levels in Patients with Diabetic Nephropathy.
AB  - INTRODUCTION: Ischemia-modified albumin (IMA) is a marker which can be associated
      with oxidative stress in various ischemic and non-ischemic processes. Oxidative
      stress plays roles in diabetes mellitus, its complications and pathogenesis.
      Serum IMA levels are examined in various clinical events. However, urine IMA
      levels have not yet been evaluated in diabetic patients. In this study, we aim to
      examine the relationship between metabolic features and urine microalbuminuria
      levels of diabetic patients and their urine IMA levels. MATERIALS AND METHODS:
      There were totally 50 type 2 diabetic patients in the study at the Mevlana
      University Hospital. Patients with cerebrovascular disease, acute myocardial
      infarction, hemodialysis patients with end stage chronic renal failure, pulmonary
      embolism, and malignant disease were excluded from the study. Metabolic features,
      urine IMA levels and cardiological parameters of patients were evaluated.
      RESULTS: Mean age of patients was 59 +/- 9 years, 20 of them (40%) were male and
      30 of them (60%) were female. There were six patients with albuminuria value of
      <0.03 mg/g (normal), there were 39 patients with microalbuminuria value of 0.03
      0.3 mg/g and there were five patients with macroalbuminuria of >0.3 mg/g.
      According to the analysis of patients with microalbuminuria (n = 39), there was
      no correlation between IMA levels and numerical demographic data, albuminuria,
      glucose, HbA1c, lipid profile, creatinine, uric acid, hematological parameters.
      DISCUSSION: Conclusively, there was no relationship between urine IMA levels and
      microalbuminuria related to the diabetic nephropathy. These findings can be
      associated with urinary excretion mechanisms of IMA.

PMID- 27696562
TI  - Combined antifungal therapy against systemic murine infections by rare
      Cryptococcus species.
AB  - Cryptococcus albidus and Cryptococcus laurentii are uncommon species of this
      genus that in recent decades have increasingly caused opportunistic infections in
      humans, mainly in immunocompromised patients; the best therapy for such infection
      being unknown. Using a murine model of systemic infection by these fungi, we have
      evaluated the efficacy of amphotericin B (AMB) at 0.8 mg/kg, administered
      intravenously, fluconazole (FLC) or voriconazole (VRC), both administered orally,
      at 25 mg/kg and the combination of AMB plus VRC against three C. albidus and two
      C. laurentii strains. All the treatments significantly reduced the fungal burden
      in all the organs studied. The combination showed a synergistic effect in the
      reduction in fungal load, working better than both monotherapies. The
      histopathological study confirmed the efficacy of the treatments.

PMID- 27696563
TI  - Antennal and mouthpart sensilla of Acanthoscelides obtectus say (Coleoptera:
      Bruchidae).
AB  - Acanthoscelides obtectus, a serious pest with a worldwide distribution, damages
      stored seeds of Phaseolus sp. To acquire a better understanding of the sensory
      orientation of bean weevils, their antennal and palpal sensilla were
      investigated. The antennae and palps possess several types of sensory hairs:
      blunt-tipped sensilla chaetica and trichoidea and also sharp-tipped sensilla
      trichoidea, these last being the most numerous. Sensilla basiconica are present
      only on the flagellomeres, but Bohm bristles occur on the basal sclerite and
      scape of the antennae. The terminal segments of the maxillary and labial palps
      bear a group of sensilla styloconica with single apical pores. Sensilla
      coeloconica are located only on the terminal palpal segments. They were unable to
      detect any distinct morphological differences between males and females. The
      possible chemosensory, mechanosensory, and thermo-/hygroreceptive functions of
      the sensilla are discussed.

PMID- 27696565
TI  - Cerebral blood flow laterality derived from arterial spin labeling as a biomarker
      for assessing the disease severity of parkinson's disease.
AB  - PURPOSE: To evaluate cerebral blood flow (CBF) laterality derived from arterial
      spin labeling (ASL) in early-stage Parkinson's disease (PD) patients compared
      with those with advanced stages. MATERIALS AND METHODS: Thirty-eight patients
      with PD (21 patients in early stages, 17 patients in advanced stages) were
      retrospectively studied. The CBF maps derived from 3T ASL data were co-registered
      to the corresponding 3DT1WI using SPM 12 software. Caudate nucleus (CN), putamen
      (PT), globus pallidus (GP), and thalamus (TH) were manually traced on the
      representative axial slices of 3DT1WI. CBF of the CN, PT, GP, and TH was measured
      using corresponding pixels on the co-registered CBF maps. A laterality index (LI)
      was calculated as the ratio of the contralateral CBF to primary affected side
      CBF. Each LI was compared between early and advanced stages of PD using the Mann
      Whitney U-test. The LIs were also compared between each stage of PD. RESULTS: In
      the CN, the LIs were significantly higher in early stages (mean LI +/- SD, 95%
      confidence interval = 1.06 +/- 0.14, 1.00-1.13) than in advanced stages (0.94 +/-
      0.14, 0.87-1.01; P < 0.05). We also observed a tendency toward decreased LIs with
      disease severity (1.10 +/- 0.14, 0.99-1.21 for Hoehn and Yahr stage I; 1.04 +/-
      0.14, 0.92-1.12 for stage II; 0.96 +/- 0.11, 0.89-1.10 for stage III; 0.93 +/-
      0.17, 0.81-1.05 for stage IV). CONCLUSION: The evaluation of CBF laterality
      pattern in the CN using ASL may be useful for assessing the disease severity of
      PD patients. LEVEL OF EVIDENCE: 3 J. MAGN. RESON. IMAGING 2017;45:1821-1826.

PMID- 27696564
TI  - A novel glycan modifies the flagellar filament proteins of the oral bacterium
      Treponema denticola.
AB  - While protein glycosylation has been reported in several spirochetes including
      the syphilis bacterium Treponema pallidum and Lyme disease pathogen Borrelia
      burgdorferi, the pertinent glycan structures and their roles remain
      uncharacterized. Herein, a novel glycan with an unusual chemical composition and
      structure in the oral spirochete Treponema denticola, a keystone pathogen of
      periodontitis was reported. The identified glycan of mass 450.2 Da is composed of
      a monoacetylated nonulosonic acid (Non) with a novel extended N7 acyl
      modification, a 2-methoxy-4,5,6-trihydroxy-hexanoyl residue in which the Non has
      a pseudaminic acid configuration (L-glycero-L-manno) and is beta-linked to serine
      or threonine residues. This novel glycan modifies the flagellin proteins (FlaBs)
      of T. denticola by O-linkage at multiple sites near the D1 domain, a highly
      conserved region of bacterial flagellins that interact with Toll-like receptor 5.
      Furthermore, mutagenesis studies demonstrate that the glycosylation plays an
      essential role in the flagellar assembly and motility of T. denticola. To our
      knowledge, this novel glycan and its unique modification sites have not been
      reported previously in any bacteria.

PMID- 27696566
TI  - Generation of RUNX3 knockout pigs using CRISPR/Cas9-mediated gene targeting.
AB  - Pigs are an attractive animal model to study the progression of cancer because of
      their anatomical and physiological similarities to human. However, the use of pig
      models for cancer research has been limited by availability of genetically
      engineered pigs which can recapitulate human cancer progression. Utilizing genome
      editing technologies such as CRISPR/Cas9 system allows us to generate genetically
      engineered pigs at a higher efficiency. In this study, specific CRISPR/Cas9
      systems were used to target RUNX3, a known tumour suppressor gene, to generate a
      pig model that can induce gastric cancer in human. First, RUNX3 knockout cell
      lines carrying genetic modification (monoallelic or biallelic) of RUNX3 were
      generated by introducing engineered CRISPR/Cas9 system specific to RUNX3 into
      foetal fibroblast cells. Then, the genetically modified foetal fibroblast cells
      were used as donor cells for somatic cell nuclear transfer, followed by embryo
      transfer. We successfully obtained four live RUNX3 knockout piglets from two
      surrogates. The piglets showed the lack of RUNX3 protein in their internal organ
      system. Our results demonstrate that the CRISPR/Cas9 system is effective in
      inducing mutations on a specific locus of genome and the RUNX3 knockout pigs can
      be useful resources for human cancer research and to develop novel cancer
      therapies.

PMID- 27696567
TI  - Phenotype and influx kinetics of leukocytes and inflammatory cytokine production
      in kidney ischemia/reperfusion injury.
AB  - BACKGROUND AND AIM: Kidney ischemia/reperfusion (IR) injury is characterized by
      tubular epithelial cell (TEC) death and an inflammatory response involving
      cytokine production and immune cell infiltration. In various kidney diseases,
      increased macrophage numbers correlate with injury severity and poor prognosis.
      However, macrophage plasticity enables a diverse range of functions, including
      wound healing, making them a key target for novel therapies. This study aimed to
      comprehensively characterize the changes in myeloid and epithelial cells and the
      production of cytokines throughout the experimental IR model of acute kidney
      injury to aid in the identification of targets to promote and enhance kidney
      regeneration and repair. METHODS: Flow cytometric analysis of murine unilateral
      IR injury was used to assess TEC and myeloid cell subpopulations in conjunction
      with histological analysis and cytokine production at 6 h, 1, 3, 5 and 7 days
      post IR injury, spanning the initial inflammatory phase and the following
      reparative phase. RESULTS: IR injury resulted in a rapid infiltration of Ly6Chigh
      monocytes and neutrophils with a steady rise in F4/80high MHCIIhigh macrophages
      over the injury time. The production of the inflammatory cytokines IL-6, MCP-1
      and TNF coincided with an increase in IL-10 production. CONCLUSION: This
      characterization will provide a reference point for future studies designed to
      manipulate immune cell phenotype and function in order to promote endogenous
      repair of damaged kidneys.

PMID- 27696568
TI  - Postural orthostatic tachycardia is not a useful diagnostic marker for chronic
      fatigue syndrome.
AB  - BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is considered a
      diagnostic marker for chronic fatigue syndrome (CFS). OBJECTIVES: The aims of
      this study were to (i) compare POTS prevalence in a CFS cohort with fatigued
      patients not meeting CFS criteria, and (ii) assess activity, impairment and
      response to cognitive behavioural therapy (CBT) in CFS patients with POTS (POTS
      CFS) and without POTS (non-POTS-CFS). METHODS: Prospective cohort study at the
      Radboud University Medical Centre in the Netherlands. Between June 2013 and
      December 2014, 863 consecutive patients with persistent fatigue were screened.
      Patients underwent an active standing test, filled out questionnaires and wore an
      activity-sensing device for a period of 12 days. RESULTS: A total of 419 patients
      with CFS and 341 non-CFS fatigued patients were included in the study. POTS
      prevalence in adult patients with CFS was 5.7% vs. 6.9% in non-CFS adults (P =
      0.54). In adolescents, prevalence rates were 18.2% and 17.4%, respectively (P =
      0.93). Adult patients with POTS-CFS were younger (30 +/- 12 vs. 40 +/- 13 years,
      P = 0.001) and had a higher supine heart rate (71 +/- 11 vs. 65 +/- 9 beats per
      min, P = 0.009) compared with non-POTS-CFS patients. Severity and activity
      patterns did not differ between groups. In patients with CFS, criteria for
      Systemic Exertion Intolerance Disease (SEID) were met in 76% of adults and 67% of
      adolescents. In these patients with CFS fulfilling the SEID criteria, the
      prevalence of POTS was not different from that in the overall CFS population.
      POTS-CFS adolescents had less clinically significant improvement after CBT than
      non-POTS-CFS adolescents (58% vs. 88%, P = 0.017). CONCLUSION: In adults with
      CFS, the prevalence of POTS was low, was not different from the rate in non-CFS
      fatigued patients and was not related to disease severity or treatment outcome.
      In POTS-CFS adolescents, CBT was less successful than in non-POTS-CFS patients.
      The evaluation of POTS appears to be of limited value for the diagnosis of CFS.

PMID- 27696570
TI  - Rapid over-the-scope-clip emergency hemostasis guidewire-assisted method for
      proximal colon Dieulafoy massive bleeding.

PMID- 27696569
TI  - Fixed-time post-cervical artificial insemination in weaned sows following
      buserelin use combined with/without eCG.
AB  - Fixed-time post-cervical artificial insemination (FTAI) drastically reduces
      labour requirements and increases the use of boars with higher genetic merit.
      This study evaluated the efficiency of eCG administration combined with/without
      the GnRH agonist buserelin for the induction and synchronization of ovulation in
      weaned sows submitted to FTAI. The sows were allocated into three groups. In the
      control group, the first artificial insemination was performed at the onset of
      oestrus and repeated every 24 hr. In the eCG+GnRH group, sows received 600 IU eCG
      at weaning and buserelin (10 MUg) after 86-89 hr of eCG, and in the GnRH group,
      sows received only buserelin after 86-89 hr of weaning. The hormone-treated sows
      received a single FTAI after 30-33 hr of buserelin application. All the sows were
      inseminated with homospermic doses (1.5 * 109  sperm cells/50 ml). The interval
      between weaning and ovulation was shorter (p < .05) in the eCG+GnRH (133.3 hr)
      and GnRH (135.9 hr) groups than the control (141.5 hr) group. In the eCG+GnRH
      group, the sows ovulated earlier (p < .05) than those in the GnRH group (44.5 vs.
      48.2 hr after buserelin administration). The reproductive performance of GnRH
      sows was not compromised when only sows exhibiting oestrus at the time of
      insemination were considered, but lower farrowing rate and smaller litter size
      were observed in eCG+GnRH sows. The reproductive performance of eCG+GnRH sows was
      primarily compromised because the insemination was performed outside the optimal
      time relative to ovulation; therefore, it is advisable to inseminate them before
      116-122 hr after weaning.

PMID- 27696571
TI  - Multilocus approaches for the measurement of selection on correlated genetic
      loci.
AB  - The study of ecological speciation is inherently linked to the study of
      selection. Methods for estimating phenotypic selection within a generation based
      on associations between trait values and fitness (e.g. survival) of individuals
      are established. These methods attempt to disentangle selection acting directly
      on a trait from indirect selection caused by correlations with other traits via
      multivariate statistical approaches (i.e. inference of selection gradients). The
      estimation of selection on genotypic or genomic variation could also benefit from
      disentangling direct and indirect selection on genetic loci. However, achieving
      this goal is difficult with genomic data because the number of potentially
      correlated genetic loci (p) is very large relative to the number of individuals
      sampled (n). In other words, the number of model parameters exceeds the number of
      observations (p ? n). We present simulations examining the utility of whole
      genome regression approaches (i.e. Bayesian sparse linear mixed models) for
      quantifying direct selection in cases where p ? n. Such models have been used for
      genome-wide association mapping and are common in artificial breeding. Our
      results show they hold promise for studies of natural selection in the wild and
      thus of ecological speciation. But we also demonstrate important limitations to
      the approach and discuss study designs required for more robust inferences.

PMID- 27696572
TI  - Distinct interferon-gamma and interleukin-9 expression in cutaneous and oral
      lichen planus.
AB  - BACKGROUND: Cutaneous (CLP) and oral lichen planus (OLP) as the main subtypes of
      lichen planus (LP) present with different clinical manifestation and disease
      course, although their histopathologic features such as the band-like lymphocyte
      infiltrate and keratinocyte apoptosis are similar. So far, the underlying
      cellular and molecular mechanisms remain poorly understood. OBJECTIVE: The aim of
      this study was to characterize and compare the in situ cellular infiltrates,
      cytokine expression profiles and apoptosis markers in CLP and OLP. METHODS: Using
      immunofluorescence staining and laser scanning microscopy, we evaluated the
      cellular infiltrate (CD1a, CD3, CD4, CD8, CD21, CD57, CD123), cytokine expression
      (interleukin (IL)-1, IL-6, IL-9, IL-10, IL-17, IL-22, IL-23, tumour necrosis
      factor-alpha, transforming growth factor-beta, interferon (IFN)-gamma), and
      apoptosis markers (Fas, Fas ligand, cleaved caspase-3, TUNEL) of 21 anonymized
      biopsy specimens of LP (11 CLP, 10 OLP). RESULTS: Among infiltrating cells mainly
      T cells and natural killer (NK) cells as well as plasmacytoid dendritic cells
      (DC) were observed. A predominance of CD8+ T cells was noted in OLP. In both CLP
      and OLP, T helper (Th)1, Th9, Th17, and Th22-type cytokines were expressed. The
      expression of IL-9, IFN-gamma and IL-22 was higher in CLP compared to that of OLP
      (P = 0.0165; P = 0.0016; P = 0.052 respectively). Expression of Fas and Fas
      ligand as well as cleaved caspase-3-positive cells was observed in the epithelium
      of all LP samples. CONCLUSIONS: The cell and cytokine patterns of CLP and OLP
      were partially distinct and generally resembled those reported for autoimmune
      diseases. The presence of CD8+ and NK cells as well as Fas/Fas ligand expression
      suggested that various pathways involved in keratinocyte apoptosis are relevant
      for LP. These results might help to establish targeted therapies for LP.

PMID- 27696573
TI  - Children referred for specialty care: Parental perspectives and preferences on
      referral, follow-up and primary care.
AB  - AIM: Over the last decade, there has been a dramatic increase in the number of
      referrals for paediatric subspecialty care and in overall appointments (new and
      review) to these doctors. We sought to determine the perspective of parents
      regarding their role in the initiation of referrals, their preferences for follow
      up and the role of general practitioners (GPs) in care co-ordination. METHODS:
      Self-completed survey in outpatient paediatric clinics (general paediatrics and
      four subspecialties) at two children's hospitals in Victoria. Recruitment targets
      were 100 parents in each of the general paediatrics clinics and 50 parents in
      each subspecialty clinic, equally divided between new and review visits (total n
      = 600). RESULTS: A total of 606 parents provided responses, with a decline rate
      of 9%. Many (52%) new patients were referred by a GP with the remainder from a
      variety of other sources. With specific regard to providing general care to their
      child, only 45% were completely confident in a GP. Most (76%) agreed with the
      statement that a GP would give their child a referral to see a paediatrician
      whenever they ask. Approximately, a third of parents reported that a GP rarely or
      never co-ordinates the care of their child with other doctors. CONCLUSIONS:
      Parents play an important role in both the initiation of paediatric specialty
      referrals and the patterns of follow-up care provided. Parent perspectives,
      preferences and motivations on both the referral process and the patterns for
      ongoing care are essential to develop policies that provide the best and most
      efficient care for children.

PMID- 27696574
TI  - Diaminodiphenylmethane Sensitization in north-eastern Italy from 1996 to 2012.
AB  - BACKGROUND: 4,4'-Diaminodiphenylmethane (DDM) is an aromatic amine used as a
      hardener, insulator and anticorrosive. Exposure implies risk of being sensitized
      and developing contact dermatitis. OBJECTIVE: The aim of this study was to
      determine the occurrence of contact sensitization to DDM among patients with
      contact dermatitis and the role of occupational exposure. PATIENTS AND METHODS:
      From 1996 to 2012, 24 056 consecutive patients with suspected allergic contact
      dermatitis were patch tested in north-eastern Italy. Individual characteristics
      were collected through a standardized questionnaire in eight departments of
      dermatology and occupational medicine. RESULTS: The overall prevalence of DDM
      sensitization was 2.5% (n = 599) with a decreasing trend in considered years.
      Trieste area had the higher prevalence of sensitization (3.2%). Mechanics and
      chemical industry workers had a significant higher risk of being sensitized to
      DDM. CONCLUSION: DDM sensitization is decreasing in years and is associated with
      some occupational exposures.

PMID- 27696575
TI  - Modulatory effects of vitamin D on peripheral cellular immunity in patients with
      recurrent miscarriage.
AB  - PROBLEM: We aimed to investigate the modulatory effects of vitamin D on
      peripheral blood cellular immune response in patients with recurrent miscarriage
      (RM). METHOD OF STUDY: The effect of vitamin D on the number of peripheral blood
      cells, T helper 1 (Th1) cytokines, and NK cytotoxicity was measured in 99 women
      with RM. RESULTS: The percentage of CD19+ B cells and NK cytotoxicity at an
      effector-to-target cell (E:T) ratio of 50:1, 25:1, and 12.5:1 were significantly
      higher in the vitamin D insufficiency group (VDI) than in the vitamin D normal
      group (VDN) (P<.05 each). The proportion of TNF-alpha-expressing Th cells was
      significantly higher in the vitamin D deficiency group (VDD) than in VDN (P<.05).
      However, there were no significant differences between VDI and VDD. This
      dysregulation was significantly reduced with 1,25(OH)2 D supplementation.
      CONCLUSION: The data suggest that the abnormalities of cellular immune response
      were observed in RM patients with a low vitamin D level, which could be regulated
      to some extent with 1,25(OH)2 D supplementation.

PMID- 27696576
TI  - Contrast-enhanced Digital Mammography: A Single-Institution Experience of the
      First 208 Cases.
AB  - Contrast-enhanced digital mammography (CEDM) is the only imaging modality that
      provides both (a) a high-resolution, low-energy image comparable to that of
      digital mammography and (b) a contrast-enhanced image similar to that of magnetic
      resonance imaging. We report the initial 208 CEDM examinations performed for
      various clinical indications and provide illustrative case examples. Given its
      success in recent studies and our experience of CEDM primarily as a diagnostic
      adjunct, CEDM can potentially improve breast cancer detection by combining the
      low-cost conclusions of screening mammography with the high sensitivity of
      magnetic resonance imaging.

PMID- 27696577
TI  - Treatment outcomes with ixekizumab in patients with moderate-to-severe psoriasis
      who have or have not received prior biological therapies: an integrated analysis
      of two Phase III randomized studies.
AB  - BACKGROUND: Biologics are effective for the treatment of psoriasis. However,
      treatment outcomes may differ among biologic-naive patients and those switched
      from previous biological therapies. OBJECTIVES: The study's objective was to
      investigate efficacy and safety of ixekizumab, a high-affinity anti-interleukin
      17A antibody, in patients with psoriasis with and without previous exposure to
      biologics. METHODS: Data were integrated from the 12-week induction phase of two
      etanercept-controlled Phase III trials. Patients received 80 mg ixekizumab every
      2 weeks (IXE Q2W; N = 736) or every 4 weeks (IXE Q4W; N = 733) following a 160-mg
      starting dose, or placebo (N = 361). Etanercept (50 mg twice weekly; N = 740) was
      administered as active control. Psoriasis Area and Severity Index (PASI) 75, PASI
      90 and PASI 100 response rates at week 12 were evaluated in patients with or
      without previous exposure to biologics. Treatment effects were analysed with the
      Cochran-Mantel-Haenszel test stratified by study; missing values were imputed as
      non-response. RESULTS: Overall, 497 (19.3%) patients had prior exposure to
      biologics and 2073 (80.7%) were naive to biologic therapy. PASI 75 was achieved
      by 91.5% of biologic-experienced patients and 87.7% of biologic-naive patients
      for IXE Q2W, 76.2% and 82.2% for IXE Q4W, respectively, and 34.6% and 50.7%,
      respectively, for etanercept. Higher response rates favouring each ixekizumab
      dose over etanercept within subgroups were also seen regarding PASI 90 and PASI
      100. CONCLUSIONS: Contrary to etanercept, the efficacy of ixekizumab was
      similarly high in patients with and without previous exposure to biologics when
      administered 80 mg every 2 weeks.

PMID- 27696578
TI  - Systematic review of psychosocial outcomes for patients with advanced melanoma.
AB  - BACKGROUND: New advanced melanoma therapies are associated with improved
      survival; however, quality of survivorship, particularly psychosocial outcomes,
      for patients overall and those treated with newer therapies is unclear.
      OBJECTIVE: Synthesize qualitative and quantitative evidence about psychosocial
      outcomes for advanced (stage III/IV) melanoma patients. METHODS: Five databases
      were searched (01/01/1980 to 31/01/2016). Inclusion criteria were as follows:
      advanced melanoma patients or sub-group analysis; assessed psychosocial outcomes;
      and English language. RESULTS: Fifty-two studies met review criteria (4
      qualitative, 48 quantitative). Trials comprise mostly medical not psychosocial
      interventions, with psychosocial outcomes assessed within broader quality of life
      measures. Patients receiving chemotherapy or IFN-alpha showed decreased emotional
      and social function and increased distress. Five trials of newer therapies
      appeared to show improvements in emotional and social function. Descriptive
      studies suggest that patients with advanced, versus localized disease, had
      decreased emotional and social function and increased distress. Contributors to
      distress were largely unexplored, and no clear framework described
      coping/adjustment trajectories. Patients with advanced versus localized disease
      had more supportive care needs, particularly amount, quality, and timing of
      melanoma-related information, communication with and emotional support from
      clinicians. Limitations included: lack of theoretical underpinnings guiding study
      design; inconsistent measurement approaches; small sample sizes; non
      representative sampling; and cross-sectional design. CONCLUSIONS: Quality trial
      evidence is needed to clarify the impact of treatment innovations for advanced
      melanoma on patients' psychosocial well-being. Survivorship research and
      subsequent translation of that knowledge into programs and services currently
      lags behind gains in the medical treatment of advanced melanoma, a troubling
      circumstance that requires immediate and focused attention.

PMID- 27696580
TI  - Goal Attainment Scaling in Individuals with Upper Limb Spasticity Post Stroke.
AB  - Focusing on rehabilitation goals is an effective approach for improving function
      in individuals with spasticity after stroke. The objectives of this study were to
      examine and map goals of post-stroke individuals with spasticity using the Goal
      Attainment Scale (GAS) and International Classification of Functioning,
      Disability and Health (ICF), and to evaluate the impact of botulinum toxin A
      (BoNTA) on occupational performance based on the type of rehabilitation goals.
      Thirty-one patients were recruited from an outpatient spasticity management
      clinic. Each patient set one goal, was injected with BoNTA in their spastic upper
      limb muscles and received standard rehabilitation services twice a week for four
      weeks. Twenty-seven participants achieved the expected level, and four exceeded
      the expected level of their rehabilitation goals. Fifty-five percent of the goals
      were related to Activity/Participation, and 45% of the goals were categorized in
      the Body Structures and Function domain of the ICF. Fifteen goals focused on
      positioning, while 16 goals focused on (independent) activities of daily living
      (ADL/IADL). Both the positioning and ADL/IADL groups experienced a reduction in
      MAS following the administration of BoNTA. The positioning group was older and
      more impaired. Mapping goals to ICF identifies specific targets for intervention,
      establishes a common language within the interdisciplinary team and
      contextualizes the ways disability impacts goals. This study is limited by a
      relatively small sample size and absence of a functional measure. Further studies
      can explore the development of goal/item banks to advance the use of GAS for
      spasticity management. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696579
TI  - The Paracoccus denitrificans NarK-like nitrate and nitrite transporters-probing
      nitrate uptake and nitrate/nitrite exchange mechanisms.
AB  - Nitrate and nitrite transport across biological membranes is often facilitated by
      protein transporters that are members of the major facilitator superfamily.
      Paracoccus denitrificans contains an unusual arrangement whereby two of these
      transporters, NarK1 and NarK2, are fused into a single protein, NarK, which
      delivers nitrate to the respiratory nitrate reductase and transfers the product,
      nitrite, to the periplasm. Our complementation studies, using a mutant lacking
      the nitrate/proton symporter NasA from the assimilatory nitrate reductase
      pathway, support that NarK1 functions as a nitrate/proton symporter while NarK2
      is a nitrate/nitrite antiporter. Through the same experimental system, we find
      that Escherichia coli NarK and NarU can complement deletions in both narK and
      nasA in P. denitrificans, suggesting that, while these proteins are most likely
      nitrate/nitrite antiporters, they can also act in the net uptake of nitrate.
      Finally, we argue that primary sequence analysis and structural modelling do not
      readily explain why NasA, NarK1 and NarK2, as well as other transporters from
      this protein family, have such different functions, ranging from net nitrate
      uptake to nitrate/nitrite exchange.

PMID- 27696582
TI  - ROR2 in the adult mouse testis.

PMID- 27696581
TI  - Predator-prey interactions amongst Permo-Triassic terrestrial vertebrates as a
      deterministic factor influencing faunal collapse and turnover.
AB  - Unlike modern mammalian communities, terrestrial Paleozoic and Mesozoic
      vertebrate systems were characterized by carnivore faunas that were as diverse as
      their herbivore faunas. The comparatively narrow food base available to
      carnivores in these paleosystems raises the possibility that predator-prey
      interactions contributed to unstable ecosystems by driving populations to
      extinction. Here, we develop a model of predator-prey interactions based on
      diversity, abundance and body size patterns observed in the Permo-Triassic
      vertebrate fossil record of the Karoo Basin, South Africa. Our simulations
      reflect empirical evidence that despite relatively high carnivore: herbivore
      species ratios, herbivore abundances were sufficient for carnivores to maintain
      required intake levels through most of the Karoo sequence. However, high
      mortality rates amongst herbivore populations, even accounting for birth rates of
      different-sized species, are predicted for assemblages immediately preceding the
      end-Guadalupian and end-Permian mass extinctions, as well as in the Middle
      Triassic when archosaurs replaced therapsids as the dominant terrestrial fauna.
      These results suggest that high rates of herbivore mortality could have played an
      important role in biodiversity declines leading up to each of these turnover
      events. Such declines would have made the systems especially vulnerable to
      subsequent stochastic events and environmental perturbations, culminating in
      large-scale extinctions.

PMID- 27696583
TI  - Yield and complications of kidney biopsy over two decades in a tertiary pediatric
      center.
AB  - BACKGROUND: Kidney biopsy serves as an adjunct for the diagnosis of renal
      disease, but it is not always productive. This study evaluated the yield and
      risks of kidney biopsies performed in 1995-2014 at a tertiary pediatric medical
      center. METHODS: The medical files of all patients who underwent closed
      percutaneous biopsy for various indications in native or transplanted kidneys
      were retrospectively reviewed for patient characteristics, technical and
      histopathologic findings, biopsy yield, and biopsy complications. Biopsy yield
      was considered positive if findings confirmed a probable diagnosis or led to a
      change in clinical diagnosis, disease severity/activity grade, treatment
      strategy, or prognosis; and negative, if findings were non-informative and in
      cases of technical failure. RESULTS: During the study period, 216 biopsies were
      performed on native kidneys and 84 on transplanted kidneys. In the transplanted
      kidney group, the most common indications for biopsy were decreased glomerular
      filtration rate and suspected rejection. Rates of positive biopsy yield were
      86.6% in the native kidney group and 82.1% in the transplanted kidney group; the
      difference was not statistically significant. Significant between-group
      differences were found in various technical and histopathological parameters,
      patient age at biopsy, and sex distribution. In the native kidney group, positive
      biopsy yield was associated with the presence of nephrotic-range proteinuria.
      Post-procedural complications occurred in three patients (1.3%) with native
      kidneys, and in one patient (1.1%) with a transplanted kidney. CONCLUSIONS:
      Kidney biopsy is an efficient and safe procedure in both native and transplanted
      kidneys and provides helpful diagnostic information in most cases in which it is
      deemed necessary.

PMID- 27696585
TI  - Loss of function of KIF1B impairs oocyte meiotic maturation and early embryonic
      development in mice.
AB  - Kinesin family member 1B (KIF1B) is an important microtubule-dependent monomeric
      motor in mammals, although little is known about its role in meiosis. We profiled
      KIF1B expression and localization during oocyte maturation and early embryonic
      development in mice, revealing a dynamic pattern throughout meiotic progression.
      Depletion or inhibition of KIF1B leads to abnormal polar body extrusion,
      disordered spindle dynamics, defects in chromosome congression, increased
      aneuploidy, and impaired embryonic development. Further, KIF1B depletion affects
      the distribution of mitochondria and abundance of ATP. Taken together, our study
      demonstrates that mouse KIF1B is important for spindle assembly, chromosome
      congression, and mitochondrial distribution during oocyte maturation and early
      embryonic development. Mol. Reprod. Dev. 83: 1027-1040, 2016 (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27696584
TI  - Sexual selection predicts brain structure in dragon lizards.
AB  - Phenotypic traits such as ornaments and armaments are generally shaped by sexual
      selection, which often favours larger and more elaborate males compared to
      females. But can sexual selection also influence the brain? Previous studies in
      vertebrates report contradictory results with no consistent pattern between
      variation in brain structure and the strength of sexual selection. We hypothesize
      that sexual selection will act in a consistent way on two vertebrate brain
      regions that directly regulate sexual behaviour: the medial preoptic nucleus
      (MPON) and the ventromedial hypothalamic nucleus (VMN). The MPON regulates male
      reproductive behaviour whereas the VMN regulates female reproductive behaviour
      and is also involved in male aggression. To test our hypothesis, we used high
      resolution magnetic resonance imaging combined with traditional histology of
      brains in 14 dragon lizard species of the genus Ctenophorus that vary in the
      strength of precopulatory sexual selection. Males belonging to species that
      experience greater sexual selection had a larger MPON and a smaller VMN.
      Conversely, females did not show any patterns of variation in these brain
      regions. As the volumes of both these regions also correlated with brain volume
      (BV) in our models, we tested whether they show the same pattern of evolution in
      response to changes in BV and found that the do. Therefore, we show that the
      primary brain nuclei underlying reproductive behaviour in vertebrates can evolve
      in a mosaic fashion, differently between males and females, likely in response to
      sexual selection, and that these same regions are simultaneously evolving in
      concert in relation to overall brain size.

PMID- 27696586
TI  - New estimate of valvuloarterial impedance in aortic valve stenosis: A cardiac
      magnetic resonance study.
AB  - PURPOSE: Valvuloarterial impedance (ZVA ), estimating left ventricle (LV)
      afterload, has been proposed in transthoracic echocardiography (TTE) as a
      predictor of mortality in aortic valve stenosis (AVS). However, its calculation
      differs from arterial characteristic impedance (ZC ). Our aim was to apply the
      concept of ZC calculation to estimate ZVA from MR with carotid tonometry and to
      evaluate these indices through their associations with symptoms, LV diastolic
      function and aortic stiffness. MATERIALS AND METHODS: In 40 patients with AVS (76
      +/- 13 years), ZVA-TI derived from velocity time integral and E/Ea were estimated
      by TTE. ZVA-INS , based on ZC formula, calculated as the instantaneous pressure
      gradient to peak flow ratio and aortic compliance were estimated by using MRI at
      1.5 Tesla. RESULTS: Both ZVA estimates were higher in symptomatic than
      asymptomatic patients (707 +/- 22 versus 579 +/- 53 dyne.s/cm5 , P = 0.031 for
      ZVA-INS and 4.35 +/- 0.16 versus 3.33 +/- 0.38 mmHg.m2 /mL, P = 0.018 for ZVA-TI
      ). Although they were both associated with aortic compliance (r = -0.45; P =
      0.006 for ZVA-INS and r = -0.43; P = 0.008 for ZVA-TI ) only ZVA-INS was
      associated with E/Ea (r = 0.50; P < 0.001). In multivariate analysis to identify
      determinants of E/Ea, a model including age, mean blood pressure, LV ejection
      fraction, LV mass, and aortic valve area was performed (R2  = 0.41; P < 0.01).
      When ZVA-INS was added to the model, its overall significance was higher R2  =
      0.56 (P < 0.01) and ZVA-INS and LV mass were the only significant determinants.
      CONCLUSION: ZVA-INS was more strongly associated with diastolic dysfunction than
      usual parameters quantifying AVS severity. This new ZVA estimate could improve LV
      afterload evaluation. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:795
      803.

PMID- 27696587
TI  - The genetic basis of local adaptation for pathogenic fungi in agricultural
      ecosystems.
AB  - Local adaptation plays a key role in the evolutionary trajectory of host-pathogen
      interactions. However, the genetic architecture of local adaptation in host
      pathogen systems is poorly understood. Fungal plant pathogens in agricultural
      ecosystems provide highly tractable models to quantify phenotypes and map traits
      to corresponding genomic loci. The outcome of crop-pathogen interactions is
      thought to be governed largely by gene-for-gene interactions. However, recent
      studies showed that virulence can be governed by quantitative trait loci and that
      many abiotic factors contribute to the outcome of the interaction. After
      introducing concepts of local adaptation and presenting examples from wild plant
      pathosystems, we focus this review on a major pathogen of wheat, Zymoseptoria
      tritici, to show how a multitude of traits can affect local adaptation.
      Zymoseptoria tritici adapted to different thermal environments across its
      distribution range, indicating that thermal adaptation may limit effective
      dispersal to different climates. The application of fungicides led to the rapid
      evolution of multiple, independent resistant populations. The degree of colony
      melanization showed strong pleiotropic effects with other traits, including trade
      offs with colony growth rates and fungicide sensitivity. The success of the
      pathogen on its host can be assessed quantitatively by counting pathogen
      reproductive structures and measuring host damage based on necrotic lesions.
      Interestingly, these two traits can be weakly correlated and depend both on host
      and pathogen genotypes. Quantitative trait mapping studies showed that the
      genetic architecture of locally adapted traits varies from single loci with large
      effects to many loci with small individual effects. We discuss how local
      adaptation could hinder or accelerate the development of epidemics in
      agricultural ecosystems.

PMID- 27696588
TI  - Telomere length reflects reproductive effort indicated by corticosterone levels
      in a long-lived seabird.
AB  - Telomere length (TL) is a candidate biomarker of ageing and phenotypic quality,
      but little is known of the (physiological) causes of TL variation. We previously
      showed that individual common terns Sterna hirundo with high reproductive success
      had short telomeres independent of age, and this pattern was particularly strong
      in the longer telomeres of the within-individual TL distribution. To test whether
      this relation can be attributed to effects of reproductive effort, we
      investigated baseline corticosterone in relation to reproductive success (number
      of fledglings) and TL. In this context, we assume that variation in baseline
      corticosterone can be interpreted as index of energy expenditure and allostatic
      load. Males with higher corticosterone levels during incubation, compared between
      and within individuals, achieved higher reproductive success and had shorter
      telomeres. The effect on telomeres was more pronounced in corticosterone measured
      later in incubation and in the longer telomeres of the within-individual TL
      distribution. Female corticosterone level during incubation was neither related
      to reproductive success nor to TL. That we observed these effects only in males
      mirrors different parental roles during reproduction in the common tern, where
      males do most of the chick provisioning. The negative association between
      reproductive success and TL suggests individual differences in reproductive
      effort as reflected in, or mediated by, baseline corticosterone. We see this
      result as a promising step towards unravelling the physiological causes of
      variation in TL and the costs of reproduction.

PMID- 27696589
TI  - Influence of sleep duration on cortical oxygenation in elderly individuals.
AB  - AIM: Short sleep duration is a risk factor for cardiovascular diseases. Cerebral
      blood flow and its regulation are affected by pathological conditions commonly
      observed in the elderly population, such as dementia, atherosclerosis, diabetes
      mellitus (DM), stroke, and hypertension. The purpose of this study was to examine
      the influence of sleep duration on cortical oxygenated hemoglobin (OxyHb) using
      near-infrared spectroscopy (NIRS). METHODS: Seventy-three individuals (age, 70.1
      +/- 3.9 years, 51 men and 22 women) participated in this study. Cortical OxyHb
      levels were measured with NIRS. We evaluated age, body mass index (BMI), smoking
      status, alcohol intake, sleep duration, hypertension, DM, and hyperlipidemia
      using a questionnaire. Blood pressure was measured using plethysmography.
      RESULTS: Peak OxyHb and area under the NIRS curve significantly decreased in
      participants with sleep duration <7 h compared with those with sleep duration >=7
      h (0.136 +/- 0.212 mM.mm vs 0.378 +/- 0.342 mM.mm, P = 0.001; 112.0 +/- 243.6 vs
      331.7 +/- 428.7, P  = 0.012, respectively). Sleep duration was significantly
      correlated with peak OxyHb level and area under the NIRS curve (r = 0.378, P  =
      0.001; r = 0.285, P  = 0.015, respectively). Multiple regression analysis,
      including age, BMI, sex, smoking status, alcohol intake, sleep duration,
      hypertension, DM, and hyperlipidemia revealed that sleep duration was the only
      significant independent factor associated with peak OxyHb and area under the NIRS
      curve (beta = 0.343, P  = 0.004; beta = 0.244, P  = 0.049, respectively), and
      smoking status was independently correlated with time to the peak OxyHb (beta = 
      0.319, P  = 0.009). CONCLUSION: Sleep duration may be an important factor that
      influences cortical oxygenation in the elderly population.

PMID- 27696590
TI  - Impedance Guided Radiofrequency Ablation for Atrial Fibrillation: Something Old
      Is New Again.

PMID- 27696591
TI  - Inflammation-induced myeloid-derived suppressor cells associated with squamous
      cell carcinoma of the head and neck.
AB  - BACKGROUND: The purpose of this study was to present our assessment of the
      significance of myeloid-derived suppressor cells (MDSCs) in head and neck
      squamous cell carcinoma (HNSCC). METHODS: We examined the percentage of MDSCs in
      the peripheral blood of patients with HNSCC. The relationship among MDSC
      recruitment, tumor progression, and cyclooxygenase (COX)-2 inhibition was also
      evaluated by animal models. RESULTS: Circulating MDSCs were significantly
      increased in patients with HNSCC compared with healthy people, and this was
      associated with the clinical tumor burden. In immunocompetent 4-nitroquinoline-1
      oxide (4-NQO)-induced oral tumor and immunocompromised tumor implantation animal
      models, MDSC recruitment was associated with the duration of 4-NQO treatment and
      tumor progression. The responsible mechanisms included the suppressive ability of
      T-cell proliferation and augmenting angiogenesis by MDSC. Blockade of COX-2
      attenuated the induction and function of MDSCs and subsequently inhibited tumor
      growth. CONCLUSION: The levels of MDSC are linked with tumor progression in
      HNSCC. Moreover, targeting COX-2 could be a promising strategy for the treatment
      of HNSCC. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 347-355, 2017.

PMID- 27696592
TI  - "Can touch this": Cross-modal shape categorization performance is associated with
      microstructural characteristics of white matter association pathways.
AB  - Previous studies on visuo-haptic shape processing provide evidence that visually
      learned shape information can transfer to the haptic domain. In particular,
      recent neuroimaging studies have shown that visually learned novel objects that
      were haptically tested recruited parts of the ventral pathway from early visual
      cortex to the temporal lobe. Interestingly, in such tasks considerable individual
      variation in cross-modal transfer performance was observed. Here, we investigate
      whether this individual variation may be reflected in microstructural
      characteristics of white-matter (WM) pathways. We first trained participants on a
      fine-grained categorization task of novel shapes in the visual domain, followed
      by a haptic categorization test. We then correlated visual training-performance
      and haptic test-performance, as well as performance on a symbol-coding task
      requiring visuo-motor dexterity with microstructural properties of WM bundles
      potentially involved in visuo-haptic processing (the inferior longitudinal
      fasciculus [ILF], the fronto-temporal part of the superior longitudinal
      fasciculus [SLFft ] and the vertical occipital fasciculus [VOF]). Behavioral
      results showed that haptic categorization performance was good on average but
      exhibited large inter-individual variability. Haptic performance also was
      correlated with performance in the symbol-coding task. WM analyses showed that
      fast visual learners exhibited higher fractional anisotropy (FA) in left SLFft
      and left VOF. Importantly, haptic test-performance (and symbol-coding
      performance) correlated with FA in ILF and with axial diffusivity in SLFft .
      These findings provide clear evidence that individual variation in visuo-haptic
      performance can be linked to microstructural characteristics of WM pathways. Hum
      Brain Mapp 38:842-854, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696593
TI  - Sex Differences in Inappropriate ICD Device Therapies: MADIT-II and MADIT-CRT.
AB  - INTRODUCTION: Approximately 10-20% of ICD recipients receive inappropriate device
      therapies. The purpose of this study was to compare the frequency of
      inappropriate therapies (IT) between men and women enrolled in MADIT II and MADIT
      CRT, and assess for potential adverse outcomes. METHODS: The electrograms for
      each ICD or CRT-D therapy, defined as either ATP or shock, were reviewed by
      adjudication committees for both studies. ICD therapy was considered
      inappropriate if it was delivered for reasons other than VT/VF. The rhythm
      triggering IT was categorized as atrial fibrillation/flutter, SVT, or
      inappropriate sensing when possible. RESULTS: One thousand nine hundred and fifty
      four men and 556 women received ICD or CRT-D devices. The risk of IT was
      significantly lower in women than men (9.2% vs. 13.5%, P = 0.006). The most
      common cause of IT in men was atrial fibrillation (38%) and SVT in women (43%).
      Inappropriate shock was not associated with increased mortality in either women
      (HR 0.82 [95% CI 0.11-6.08]; P = NS) or men (HR 1.37 [95% CI 0.75-2.48]; P = NS)
      by multivariate analysis. Conversely, appropriate shock therapy strongly
      correlated with increased risk of death during subsequent post-shock follow-up in
      women (HR 5.99 [95% CI 2.75-13.02]; P < 0.0001) and men (HR 2.61 [95% CI 1.82
      3.74]; P < 0.0001). CONCLUSIONS: Women experience significantly less IT than men,
      partially explained by the increased frequency of atrial fibrillation in men. IT
      was not associated with increased mortality in either sex. Appropriate shock
      therapy was a strong predictor of death in both, with women showing a 2-fold
      higher risk than men during post-shock long-term follow-up.

PMID- 27696594
TI  - Comparative study of host response to chytridiomycosis in a susceptible and a
      resistant toad species.
AB  - In the past century, recently emerged infectious diseases have become major
      drivers of species decline and extinction. The fungal disease chytridiomycosis
      has devastated many amphibian populations and exacerbated the amphibian
      conservation crisis. Biologists are beginning to understand what host traits
      contribute to disease susceptibility, but more work is needed to determine why
      some species succumb to chytridiomycosis while others do not. We conducted an
      integrative laboratory experiment to examine how two toad species respond to
      infection with the pathogen Batrachochytrium dendrobatidis in a controlled
      environment. We selected two toad species thought to differ in susceptibility -
      Bufo marinus (an invasive and putatively resistant species) and Bufo boreas (an
      endangered and putatively susceptible species). We measured infection intensity,
      body weight, histological changes and genomewide gene expression using a custom
      assay developed from transcriptome sequencing. Our results confirmed that the two
      species differ in susceptibility with the more susceptible species, B. boreas,
      showing higher infection intensities, loss in body weight, more dramatic
      histological changes and larger perturbations in gene expression. We found key
      differences in skin expression responses in multiple pathways including
      upregulation of skin integrity-related genes in the resistant B. marinus.
      Together, our results show intrinsic differences in host response between related
      species, which are likely to be important in explaining variation in response to
      a deadly emerging pathogen in wild populations. Our study also underscores the
      importance of understanding differences among host species to better predict
      disease outcomes and reveal generalities about host response to emerging
      infectious diseases of wildlife.

PMID- 27696595
TI  - Copy number profiling of tumor suppressor genes in head and neck cancer.
AB  - BACKGROUND: Sensitive and reliable new biomarkers are needed in head and neck
      cancer to predict the outcome and for therapy that is more effective. Copy number
      alterations are frequent and play a critical role in cancer. METHODS: Copy number
      alterations of 24 tumor suppressor genes in head and neck cancer were analyzed
      simultaneously in matched tumor and normal samples from 93 patients using
      multiplex ligation-dependent probe amplification (MLPA). RESULTS: Chromosomes 3p
      and 9p displayed the most common alterations. The gene displaying most frequent
      losses was the mutL homolog 1 (MLH1) gene, followed by the cyclin-dependent
      kinase inhibitor 2A (CDKN2A) and CDKN2B genes. A significant correlation was
      observed between the CDKN2A and CDKN2B genes. The tissue inhibitor of
      metalloproteinase (TIMP)3 gene alterations were observed in 8 tumors. CONCLUSION:
      Our data confirm previous observations and suggest that losses of the MLH1 and
      CDKN2 genes and alterations of the TIMP3 gene play an important role in head and
      neck carcinogenesis. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 341-346,
      2017.

PMID- 27696596
TI  - Baclofen Solution for Low-Volume Therapeutic Delivery.
AB  - OBJECTIVES: Baclofen is a zwitterion molecule where increased ions in the
      excipient increase the solubility. We developed baclofen in a stable solution
      similar to cerebrospinal fluid (CSF) without bicarbonate and proteins to improve
      the solubility of the baclofen and to reduce the potential toxicity to the
      central nervous system (CNS) and subarachnoid space. The objective is to develop
      a solution of baclofen wherein baclofen is solubilized in a multivalent
      physiological ion solution such as artificial cerebrospinal fluid (aCSF) at a
      concentration from 2 mg/cc to 10 mg/cc. METHODS: First, to determine the
      solubility of Baclofen in aCSF, solubility was determined at six different pH
      levels at 37 degrees C, by the addition of aCSF to a known amount of Baclofen.
      The final concentrations were confirmed by high performance liquid chromatography
      (HPLC) analysis. Second, the stability of Baclofen at 4 mg/cc investigated in a
      test manufacturing batch utilizing standard methods of production of 1500 20 cc
      vials inverted for 18 months at 25 degrees C at 60% humidity. The stability and
      purity of the baclofen was verified at 18 months by HPLC analysis. RESULTS:
      Baclofen was initially soluble between pH of 6-8 above 7 mg/cc but fell back to
      6.3-5.8 mg/cc level with time. Baclofen produced in vials with inversion were
      noted to be stable at 4 mg/cc at 18 months with less than 2% breakdown of the
      baclofen in solution. CONCLUSION: Baclofen is much more soluble in artificial CSF
      than normal saline. The artificial CSF may also be less toxic to the subarachnoid
      space than saline.

PMID- 27696598
TI  - Preschool and School Phases of Postmaxillectomy Prosthetic Rehabilitation in a
      Child: A Clinical Report.
AB  - This report describes the postmaxillectomy prosthetic rehabilitation of a child
      with maxillary chondrosarcoma over an 8-year period. Specifically, it (1)
      describes the planning and rehabilitation procedures carried out during the
      period from before the operation to the time when the patient started elementary
      school and (2) reports the results of evaluations of the patient's oral and
      psychosocial function conducted during the school phase. The prosthetic treatment
      plan was separated into two phases (the preschool and school phases) and was
      started prior to surgery, when an immediate surgical obturator was designed by
      the surgeons. After the operation, it was considered important to provide the
      patient and her mother with training regarding how the defect should be cleaned,
      trismus prevention, and how the prosthesis should be fitted. In addition,
      esthetic improvements and the ability to speak clearly were also targeted during
      treatment planning. After surgery, obturators were fabricated in a conventional
      manner and fitted at the ages of 2, 4, 6, 8, and 10 years. The patient's oral
      function during the use of the obturators was evaluated objectively. Marked
      improvements in oral function were seen during both treatment phases. The
      patient's ability to perform psychosocial functions at school also improved
      during the use of the obturators.

PMID- 27696597
TI  - The fungal cultivar of leaf-cutter ants produces specific enzymes in response to
      different plant substrates.
AB  - Herbivores use symbiotic microbes to help derive energy and nutrients from plant
      material. Leaf-cutter ants are a paradigmatic example, cultivating their
      mutualistic fungus Leucoagaricus gongylophorus on plant biomass that workers
      forage from a diverse collection of plant species. Here, we investigate the
      metabolic flexibility of the ants' fungal cultivar for utilizing different plant
      biomass. Using feeding experiments and a novel approach in metaproteomics, we
      examine the enzymatic response of L. gongylophorus to leaves, flowers, oats or a
      mixture of all three. Across all treatments, our analysis identified and
      quantified 1766 different fungal proteins, including 161 putative biomass
      degrading enzymes. We found significant differences in the protein profiles in
      the fungus gardens of subcolonies fed different plant substrates. When provided
      with leaves or flowers, which contain the majority of their energy as
      recalcitrant plant polymers, the fungus gardens produced more proteins predicted
      to break down cellulose: endoglucanase, exoglucanase and beta-glucosidase.
      Further, the complete metaproteomes for the leaves and flowers treatments were
      very similar, while the mixed substrate treatment closely resembled the treatment
      with oats alone. This indicates that when provided a mixture of plant substrates,
      fungus gardens preferentially break down the simpler, more digestible substrates.
      This flexible, substrate-specific enzymatic response of the fungal cultivar
      allows leaf-cutter ants to derive energy from a wide range of substrates, which
      likely contributes to their ability to be dominant generalist herbivores.

PMID- 27696599
TI  - Corrigendum.

PMID- 27696600
TI  - Effects of increasing root carbon investment on the mortality and resprouting of
      Haloxylon ammodendron seedlings under drought.
AB  - Tree mortality induced by drought is one of the most complex processes in
      ecology. Although two mechanisms associated with water and carbon balance are
      proposed to explain tree mortality, outstanding problems still exist. Here, in
      order to test how the root system benefits survival and resprouting of Haloxylon
      ammodendron seedlings, we examined the various water- and carbon-related
      physiological indicators (shoot water potential, photosynthesis, dark
      respiration, hydraulic conductance and non-structural carbohydrates [NSC]) of H.
      ammodendron seedlings, which were grown in drought and control conditions
      throughout a grow season in greenhouse. The survival time of the seedling root
      system (died 70 days after drought) doubled the survival time of the shoot (died
      at 35 days). Difference in survival time between shoot and root resulted from
      sustained root respiration supported by increased NSC in roots under drought.
      Furthermore, investment into the root contributed to resprouting following
      drought. Based on these results, a death criterion is proposed for this species.
      The time sequence of major events indicated that drought shifted carbon
      allocation between shoot and root and altered the flux among different sinks
      (growth, respiration or storage). The interaction of water and carbon processes
      determined death or survival of droughted H. ammodendron seedlings. These
      findings revealed that the 'root protection' strategy is critical in determining
      survival and resprouting of this species, and provided insights into the effects
      of carbon and water dynamics on tree mortality.

PMID- 27696601
TI  - Disseminated nocardiosis after unrelated bone marrow transplantation.
AB  - Nocardiosis is a rare bacterial infection occurring mainly in patients with
      deficient cell-mediated immunity. Although disseminated nocardiosis after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a rare
      complication, it is associated with high mortality. Moreover, after allo-HSCT,
      nocardiosis may be mistaken for other bacterial or fungal infections because
      clinical and radiographic findings of pulmonary, cerebral, and cutaneous
      nocardiosis lesions are non-specific. Here, we report a case of disseminated
      nocardiosis (caused by Nocardia abscessus) with skin, pulmonary, liver, lymph
      node, and multiple brain abscesses in a patient after allo-HSCT. The patient
      initially responded clinically and radiographically to imipenem/cilastin and
      trimethoprim-sulfamethoxazole therapy. Clinicians should be aware of the
      possibility of nocardiosis in allo-HSCT recipients who are treated with multiple
      immunosuppressive agents to control chronic graft-versus-host disease. Accurate
      diagnosis and identification of disseminated nocardiosis is important to ensure
      administration of the correct antibiotic regimen.

PMID- 27696602
TI  - Killing the spores of Bacillus species by molecular iodine.
AB  - AIMS: To determine the responses of spores of Bacillus subtilis and Bacillus
      anthracis surrogate Bacillus thuringiensis Al Hakam to I2 treatment. METHODS AND
      RESULTS: Spores of B. subtilis and B. thuringiensis killed by aqueous 30 degrees
      C-I2 could germinate, and their inner membrane (IM) was intact. Spore coats were
      important in I2 resistance, DNA-protective proteins were not important, and
      survivors of I2 treatment were not mutagenized. Viabilities of I2 -treated, 90
      98% killed spores were much lower on high-salinity media, and the treated spores
      were more heat sensitive than the untreated spores. Germinated I2 -killed spores
      were dead as determined by staining with nucleic acid dyes, and many appeared to
      have been lysed. CONCLUSIONS: Aqueous I2 appeared to kill B. subtilis and B.
      thuringiensis spores such that spores lyse soon after they germinate, and not by
      causing DNA damage or rupture of spores' IM. I2 treatment also generated many
      damaged spores that could only be recovered under nonstressful conditions.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This work shows that spores of the model
      organism B. subtilis, and B. thuringiensis, a surrogate for B. anthracis spores,
      exhibit similar mechanisms of resistance to and killing by I2 . Generation by I2
      treatment of conditionally dead spores indicates that appropriate media are
      essential to efficiently enumerate viable I2 -treated spores.

PMID- 27696603
TI  - Enhanced subject-specific resting-state network detection and extraction with
      fast fMRI.
AB  - Resting-state networks have become an important tool for the study of brain
      function. An ultra-fast imaging technique that allows to measure brain function,
      called Magnetic Resonance Encephalography (MREG), achieves an order of magnitude
      higher temporal resolution than standard echo-planar imaging (EPI). This new
      sequence helps to correct physiological artifacts and improves the sensitivity of
      the fMRI analysis. In this study, EPI is compared with MREG in terms of
      capability to extract resting-state networks. Healthy controls underwent two
      consecutive resting-state scans, one with EPI and the other with MREG. Subject
      level independent component analyses (ICA) were performed separately for each of
      the two datasets. Using Stanford FIND atlas parcels as network templates, the
      presence of ICA maps corresponding to each network was quantified in each
      subject. The number of detected individual networks was significantly higher in
      the MREG data set than for EPI. Moreover, using short time segments of MREG data,
      such as 50 seconds, one can still detect and track consistent networks. Fast fMRI
      thus results in an increased capability to extract distinct functional regions at
      the individual subject level for the same scan times, and also allow the
      extraction of consistent networks within shorter time intervals than when using
      EPI, which is notably relevant for the analysis of dynamic functional
      connectivity fluctuations. Hum Brain Mapp 38:817-830, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27696604
TI  - Central circuitry responsible for the divergent sympathetic responses to tonic
      muscle pain in humans.
AB  - Experimentally induced tonic muscle pain evokes divergent muscle vasoconstrictor
      responses, with some individuals exhibiting a sustained increase in muscle
      sympathetic nerve activity (MSNA), and others a sustained decrease. These
      patterns cannot be predicted from an individual's baseline physiological or
      psychological measures. The aim of this study was to investigate whether the
      different muscle sympathetic responses to tonic muscle pain were associated with
      differential changes in regional brain activity. Functional magnetic resonance
      imaging (fMRI) of the brain was performed concurrently with microelectrode
      recording of MSNA from the peroneal nerve during a 40-min infusion of hypertonic
      saline into the ipsilateral tibialis anterior muscle. MSNA increased in 26 and
      decreased in 11 of 37 subjects during tonic muscle pain. Within the prefrontal
      and cingulate cortices, precuneus, nucleus accumbens, caudate nucleus, and
      dorsomedial hypothalamus, blood oxygen level dependent (BOLD) signal intensity
      increased in the increasing-MSNA group and remained at baseline or decreased in
      the decreasing-MSNA group. Similar responses occurred in the dorsolateral pons
      and in the region of the rostral ventrolateral medulla. By contrast, within the
      region of the dorsolateral periaqueductal gray (dlPAG) signal intensity initially
      increased in both groups but returned to baseline levels only in the increasing
      MSNA group. These results suggest that the divergent sympathetic responses to
      muscle pain result from activation of a neural pathway that includes the dlPAG,
      an area thought to be responsible for the behavioral and cardiovascular responses
      to psychological rather than physical stressors. Hum Brain Mapp 38:869-881, 2017.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27696606
TI  - Secretory glands and microvascular systems imaged in aqueous solution by
      atmospheric scanning electron microscopy (ASEM).
AB  - Exocrine glands, e.g., salivary and pancreatic glands, play an important role in
      digestive enzyme secretion, while endocrine glands, e.g., pancreatic islets,
      secrete hormones that regulate blood glucose levels. The dysfunction of these
      secretory organs immediately leads to various diseases, such as diabetes or
      Sjogren's syndrome, by poorly understood mechanisms. Gland-related diseases have
      been studied by optical microscopy (OM), and at higher resolution by transmission
      electron microscopy (TEM) of Epon embedded samples, which necessitates
      hydrophobic sample pretreatment. Here, we report the direct observation of tissue
      in aqueous solution by atmospheric scanning electron microscopy (ASEM). Salivary
      glands, lacrimal glands, and pancreas were fixed, sectioned into slabs, stained
      with phosphotungstic acid (PTA), and inspected in radical scavenger d-glucose
      solution from below by an inverted scanning electron microscopy (SEM), guided by
      optical microscopy from above to target the tissue substructures. A 2- to 3-um
      specimen thickness was visualized by the SEM. In secretory cells, cytoplasmic
      vesicles and other organelles were clearly imaged at high resolution, and the
      former could be classified according to the degree of PTA staining. In islets of
      Langerhans, the microvascular system used as an outlet by the secretory cells was
      also clearly observed. Microvascular system is also critically involved in the
      onset of diabetic complications and was clearly visible in subcutaneous tissue
      imaged by ASEM. The results suggest the use of in-solution ASEM for histology and
      to study vesicle secretion systems. Further, the high-throughput of ASEM makes it
      a potential tool for the diagnosis of exocrine and endocrine-related diseases.

PMID- 27696605
TI  - Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly.
AB  - OBJECTIVE: The objective of this study was to relate a novel test of identifying
      and recalling odor percepts to biomarkers of Alzheimer's disease (AD) in well
      characterized elderly individuals, ranging from cognitively normal to demented.
      METHODS: One hundred eighty-three participants (cognitively normal: n = 70;
      subjective cognitive concerns: n = 74; mild cognitive impairment [MCI]: n = 29,
      AD dementia: n = 10) were administered novel olfactory tests: the Odor Percept
      IDentification (OPID) and the Percepts of Odor Episodic Memory (POEM) tests.
      Univariate cross-sectional analyses of performance across diagnoses; logistic
      regression modeling, including covariates of age, sex, education, APOE genotype,
      and neuropsychological test scores; and linear mixed modeling of longitudinal
      cognitive scores were performed. Amyloid deposition and MRI volumetrics were
      analyzed in a subset of participants. RESULTS: Accuracy of identification and
      episodic memory of odor percepts differed significantly across diagnosis and age,
      with progressively worse performance across degrees of impairment. Among the
      participants who were cognitively normal or had subjective cognitive concerns,
      poorer than expected performance on the POEM test (based on the same individual's
      performance on the OPID and odor discrimination tests) was associated with higher
      frequencies of the APOE epsilon4 allele, thinner entorhinal cortices, and worse
      longitudinal trajectory of Logical Memory scores. INTERPRETATION: Selective
      impairment of episodic memory of odor percepts, relative to identification and
      discrimination of odor percepts revealed by this novel POEM battery, is
      associated with biomarkers of AD in a well-characterized pre-MCI population.
      These affordable, noninvasive olfactory tests offer potential to identify
      clinically normal individuals who have greater likelihood of future cognitive
      decline. Ann Neurol 2016;80:846-857.

PMID- 27696607
TI  - The Volume-Outcome Effect: Impact on Trial-to-Permanent Conversion Rates in
      Spinal Cord Stimulation.
AB  - OBJECTIVES: Conversion rates from trial leads to permanent spinal cord
      stimulation (SCS) systems have important implications for healthcare resource
      utilization (HCRU) and pain management. We hypothesized that there is a volume
      outcome effect, with chronic pain patients who visit high volume SCS implanters
      will have higher trial-to-permanent conversion rates. MATERIALS AND METHODS: We
      designed a large, retrospective analysis using the Truven MarketScan database
      analyzing adult SCS patients with provider information available, with or without
      IPG implantation from the years 2007 to 2012 was designed. Patients were divided
      into three provider-based groups: high (>25), medium (9-24), and low (3-8) volume
      providers. Univariate and multivariate models identified factors associated with
      successful conversion. RESULTS: A total of 17,850 unique trial implants were
      performed by 3028 providers. Of 13,879 patients with baseline data available,
      8981 (64.7%) progressed to permanent SCS. Higher volume providers were associated
      with slightly higher conversion rates (65.9% vs. 63.3% low volume, p = 0.029),
      explant rates (9.2% vs. 7.7% medium volume, p = 0.026), younger age (52.0 +/-
      13.4 years vs. 53.0 +/- 13.4 years, p = 0.0026), Medicare/Medicaid (47.8% vs.
      35.0% low volume, p < 0.0001), Southern region (53.5% vs. 38.9% low volume, p <
      0.0001), and higher Charlson comorbidity scores (1.0 [SD = 1.4], p = 0.0002).
      Multivariate regression results showed female gender (1.13 [95% CI: 1.05-1.22], p
      < 0.001) and high volume providers associated with higher odds of successful
      trial conversion (1.12 [95% CI: 1.02-1.22], p = 0.014). CONCLUSIONS: In this
      nationwide analysis, high volume providers achieved higher trial-to-permanent SCS
      conversion rates than lower volume providers. The study has implications for both
      training requirements and referral patterns to delineate minimum implant
      experience necessary for provider proficiency. Future studies may be useful to
      understand HCRU differences.

PMID- 27696608
TI  - Repetitive DNA methylome analysis by small-scale and single-cell shotgun
      bisulfite sequencing.
AB  - Whole-genome shotgun bisulfite sequencing (WG-SBS) is currently the most powerful
      tool available for understanding genomewide cytosine methylation with single-base
      resolution; however, the high sequencing cost limits its widespread application,
      particularly for mammalian genomes. We mapped high- to low-coverage SBS short
      reads of mouse and human female developing germ cells to consensus sequences of
      repetitive elements that were multiplied in the respective host genome. This
      mapping strategy effectively identified active and evolutionarily young
      retrotransposon subfamilies and centromeric satellite repeats that were resistant
      to DNA demethylation during the investigated progressive stages of germ cell
      development. Notably, quantities of only tens of thousands of uniquely mapped
      reads provided sufficient sensitivity to allow for methylation analyses of
      multiple retrotransposons and satellite repeats in mice. Furthermore, we produced
      SBS results from single female murine germ cells by an improved multiplexing and
      amplification-free SBS method (scPBAT). The scPBAT results quantitatively
      provided >=5* sequencing coverage for at least 30 repeats, and the individual
      methylation patterns detected were similar to the bulk cell-based results. Our
      single-cell methylome sequencing technique will allow researchers to investigate
      intergenic methylation characteristics from limited amounts of mammalian cells as
      well as cells from other organisms with genomic annotations.

PMID- 27696609
TI  - Response to the validity and reliability of a signal impact assessment tool:
      statistical issue to avoid misinterpretation.

PMID- 27696610
TI  - The validity and reliability of a signal impact assessment tool: statistical
      issue to avoid misinterpretation.

PMID- 27696612
TI  - Breast Disease Treatment in a US Military Hospital in Afghanistan.

PMID- 27696611
TI  - PRDM1/BLIMP1 is widely distributed to the nascent fetal-placental interface in
      the mouse gastrula.
AB  - BACKGROUND: PRDM1 is a transcriptional repressor that contributes to primordial
      germ cell (PGC) development. During early gastrulation, epiblast-derived PRDM1 is
      thought to be restricted to a lineage-segregated germ line in the allantois.
      However, given recent findings that PGCs overlap an allantoic progenitor pool
      that contributes widely to the fetal-umbilical interface, posterior PRDM1 may
      also contribute to soma. RESULTS: Within the posterior mouse gastrula (early
      streak, 12-s stages, embryonic days ~6.75-9.0), PRDM1 localized to all tissues
      containing putative PGCs; however, PRDM1 was also found in all three primary germ
      layers, their derivatives, and two presumptive growth centers, the allantoic core
      domain and ventral ectodermal ridge. While PRDM1 and STELLA colocalized
      predominantly within the hindgut, where putative PGCs reside, other colocalizing
      cells were found in non-PGC sites. Additional PRDM1 and STELLA cells were found
      independent of each other throughout the posterior region, including the hindgut.
      The Prdm1-Cre-driven reporter supported PRDM1 localization in the majority of
      sites; however, some Prdm1 descendants were found in sites independent of PRDM1
      protein, including allantoic mesothelium and hindgut endoderm. CONCLUSIONS:
      Posterior PRDM1 contributes more broadly to the developing fetal-maternal
      connection than previously recognized, and PRDM1 and STELLA, while overlapping in
      putative PGCs, also co-localize in several other tissues. Developmental Dynamics
      246:50-71, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696613
TI  - Implicit and explicit false belief development in preschool children.
AB  - The ability to represent the mental states of other agents is referred to as
      Theory of Mind (ToM). A developmental breakthrough in ToM consists of
      understanding that others can have false beliefs about the world. Recently,
      infants younger than 2 years of age have been shown to pass novel implicit false
      belief tasks. However, the processes underlying these tasks and their relation to
      later-developing explicit false belief understanding, as well as to other
      cognitive abilities, are not yet understood. Here, we study a battery of implicit
      and explicit false belief tasks in 3- and 4-year-old children, relating their
      performance to linguistic abilities and executive functions. The present data
      show a significant developmental change from failing explicit false belief tasks
      at 3 years of age to passing them at the age of 4, while both age groups pass
      implicit false belief tasks. This differential developmental trajectory is
      reflected by the finding that explicit and implicit false belief tasks do not
      correlate. Further, we demonstrate that explicit false belief tasks correlate
      with syntactic and executive functions, whereas implicit false belief tasks do
      not. The study thus indicates that the processes underlying implicit false belief
      tasks are different from later-developing explicit false belief understanding.
      Moreover, our results speak for a critical role of syntactic and executive
      functions for passing standard explicit false belief tasks in contrast to
      implicit tasks.

PMID- 27696614
TI  - Leading and advocating for global health competencies: a nursing challenge.

PMID- 27696615
TI  - Elastic Properties of Lithium Disilicate Versus Feldspathic Inlays: Effect on the
      Bonding by 3D Finite Element Analysis.
AB  - PURPOSE: To determine the elastic properties of five ceramic systems with
      different compositions (lithium disilicate vs. feldspathic ceramics) and
      processing methods and compare the stress distribution in premolars in the
      interface with inlays made with these systems loaded with the maximum normal bite
      force (665 N) using 3D finite element analysis (FEA). MATERIALS AND METHODS: The
      elastic properties of five ceramic restoration materials (IPS e.max Press, IPS
      e.max CAD, Vita PM9, Vita Mark II, Vita VM7) were obtained using the ultrasonic
      pulse-echo method. Three-dimensional FEA simplified models of maxillary premolars
      restored with these ceramic materials were created. The models were loaded with a
      load at the two nodes on the occlusal surface in the middle of the tooth, 2 mm
      from the outside of the tooth, simulating a loading ball with a radius of 6 mm.
      RESULTS: The means values of density (g/cm3), Young's modulus (GPa), and Poison's
      ratio was 2.6 +/- 0.3, 82.3 +/- 18.3, and 0.22 +/- 0.01 for IPS e.max Press; 2.3
      +/- 0.1, 83.5 +/- 15.0, and 0.21 +/- 0.01 for IPS e.max CAD; 2.5 +/- 0.1, 44.4 +/
      11.5, and 0.26 +/- 0.08 for PM9; 2.4 +/- 0.1, 70.6 +/- 4.9, and 0.22 +/- 0.01
      for Vitamark II; 2.4 +/- 0.1, 63.3 +/- 3.9, and 0.23 +/- 0.01 for VM7,
      respectively. The 3D FEA showed the tensile stress at the interface between the
      tooth and the inlay was dependent on the elastic properties of the materials,
      since the Vita PM9 and IPS e.max CAD ceramics presented the lowest and the
      highest stress concentration in the interface, respectively. CONCLUSIONS: The
      elastic properties of ceramic materials were influenced by composition and
      processing methods, and these differences influenced the stress concentration at
      the bonding interface between tooth and restoration. The lower the elastic
      modulus of inlays, the lower is the stress concentration at the bonding
      interfaces.

PMID- 27696616
TI  - Diagnostic value of gadobutrol versus gadopentetate dimeglumine in enhanced MRI
      of brain metastases.
AB  - PURPOSE: To compare gadobutrol and gadopentetate dimeglumine (Gd-DTPA) contrast
      enhanced magnetic resonance imaging (MRI) at 3T for visualizing brain metastases.
      MATERIALS AND METHODS: The present randomized study included 60 consecutive
      patients with known or suspected brain metastases from systemic malignancies. Two
      enhanced cerebral MR scans were performed in each patient within an interval of 2
      5 days using different contrast agents (gadobutrol or Gd-DTPA) at 3T. The dose of
      the contrast agents (0.1 mmol/kg Gd) was also identical. The axial T1 FLAIR
      images at 3, 7, and 10 minutes after the injection of the contrast agent were
      obtained for evaluation. Two experienced radiologists performed subjective
      evaluation of the image quality, made the choice of the optimal images, and
      performed an objective evaluation including: signal-to-noise ratio (SNR) of the
      brain metastases, contrast-to-noise ratio (CNR), contrast enhancement (CE),
      contrast-to-brain ratio (CBR), and contrast enhancement ratio (CER) of the brain
      metastases. RESULTS: Subjective evaluation showed that at 3, 7, and 10 minutes
      gadobutrol elicited higher scores (margin score: 3.56 +/- 0.74 vs. 3.33 +/- 0.93,
      3.68 +/- 0.57 vs. 3.45 +/- 0.81, 3.58 +/- 0.71 vs. 3.43 +/- 0.76; interior score:
      2.83 +/- 0.42 vs. 2.63 +/- 0.61, 2.86 +/- 0.38 vs. 2.73 +/- 0.52, 2.80 +/- 0.42
      vs. 2.69 +/- 0.53; and overall score: 4.42 +/- 0.98 vs. 4.09 +/- 1.19, 4.57 +/-
      0.75 vs. 4.26 +/- 1.05, 4.48 +/- 0.83 vs. 4.21 +/- 1.03, respectively) in
      displaying the details and overall lesions than Gd-DTPA (repeated measures
      analysis of variance [ANOVA], margin score: P = 0.001, < 0.0001, 0.006; interior
      score: P < 0.0001, 0.004, 0.009; and overall score: P = 0.001, < 0.0001, <
      0.0001, respectively). Subjective optimal image evaluation showed that the
      percentage of image assessed as "gadobutrol was better than Gd-DTPA (41.2-44.1%)"
      was greater than that assessed as "Gd-DTPA was better than gadobutrol (5.9
      26.5%)." Objective evaluation showed that at 3, 7, and 10 minutes the SNR (214.17
      +/- 85.70 vs. 199.57 +/- 85.08, 214.80 +/- 86.03 vs. 199.19 +/- 84.74, and 213.83
      +/- 82.46 vs. 193.68 +/- 79.59, respectively), CNR (68.64 +/- 50.18 vs. 57.88 +/-
      51.06, 75.42 +/- 53.19 vs. 63.74 +/- 53.91, and 77.13 +/- 51.86 vs. 63.21 +/-
      51.71, respectively), CE (101.76 +/- 63.31 vs. 87.61 +/- 64.85, 99.85 +/- 61.56
      vs. 85.08 +/- 64.98, and 100.33 +/- 58.63 vs. 82.73 +/- 61.73, respectively), CBR
      (0.48 +/- 0.32 vs. 0.40 +/- 0.33, 0.54 +/- 0.34 vs. 0.46 +/- 0.35, and 0.56 +/-
      0.34 vs. 0.47 +/- 0.34, respectively), and CER (0.99 +/- 0.69 vs. 0.88 +/- 0.81,
      0.97 +/- 0.68 vs. 0.86 +/- 0.84, and 0.98 +/- 0.65 vs. 0.85 +/- 0.80,
      respectively) were all higher when using gadobutrol compared with Gd-DTPA in the
      enhanced MR (repeated measures ANOVA, all P < 0.0001). On Gd-DTPA enhanced
      images, 289, 292, and 292 lesions at 3, 7, and 10 minutes were detected by the
      two radiologists, while 295, 301, and 301 lesions were detected on gadobutrol
      enhanced images, respectively. CONCLUSION: Using a 3T T1 FLAIR sequence,
      gadobutrol (0.1 mmol/kg body weight)-enhanced MR resulted in more conspicuous
      brain metastases, and more metastases compared with the same dose of Gd-DTPA. A
      delay time of 7 minutes for postcontrast MRI in patients with brain metastases is
      suggested in clinical practice. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING
      2017;45:1827-1834.

PMID- 27696618
TI  - The high-diagnostic characteristics of HBsAg level in differentiation of
      hepatitis B clinical presentations: Myth or truth?

PMID- 27696621
TI  - Para-Hisian Pacing: A Paradoxical Response?

PMID- 27696620
TI  - ERK activation in endothelial cells is a novel marker during neovasculogenesis.
AB  - Vasculogenesis is essential during early development to construct networks
      transporting oxygen, blood and nutrients. Tip and stalk cells are specialized
      endothelial cells involved in novel vessel formation because of their behavior
      such as sprouting as a leading cell and following tip cell. However, the
      spatiotemporal details determining the emergence of these cells are unknown.
      Here, we first show that the ERK activity in endothelial cells represents the
      precursor of tip and stalk cells for vasculogenesis in zebrafish. We identified
      that tip and stalk cells for intersegmental vessel (ISV) formation were already
      specialized in the dorsal aorta (DA) before sprouting. Furthermore, similar
      specialization was observed in tip cells during parachordal vessel (PAV)
      formation in lymphangiogenesis. We also identified that the ERK activity was
      required for specialized cells to emerge from existing blood vessels. Our data
      show that the ERK activity is a novel marker for determining the emergence of
      cells in both angiogenesis and lymphangiogenesis.

PMID- 27696619
TI  - Genotyping-by-sequencing approaches to characterize crop genomes: choosing the
      right tool for the right application.
AB  - In the last decade, the revolution in sequencing technologies has deeply impacted
      crop genotyping practice. New methods allowing rapid, high-throughput genotyping
      of entire crop populations have proliferated and opened the door to wider use of
      molecular tools in plant breeding. These new genotyping-by-sequencing (GBS)
      methods include over a dozen reduced-representation sequencing (RRS) approaches
      and at least four whole-genome resequencing (WGR) approaches. The diversity of
      methods available, each often producing different types of data at different
      cost, can make selection of the best-suited method seem a daunting task. We
      review the most common genotyping methods used today and compare their
      suitability for linkage mapping, genomewide association studies (GWAS), marker
      assisted and genomic selection and genome assembly and improvement in crops with
      various genome sizes and complexity. Furthermore, we give an outline of
      bioinformatics tools for analysis of genotyping data. WGR is well suited to
      genotyping biparental cross populations with complex, small- to moderate-sized
      genomes and provides the lowest cost per marker data point. RRS approaches differ
      in their suitability for various tasks, but demonstrate similar costs per marker
      data point. These approaches are generally better suited for de novo applications
      and more cost-effective when genotyping populations with large genomes or high
      heterozygosity. We expect that although RRS approaches will remain the most cost
      effective for some time, WGR will become more widespread for crop genotyping as
      sequencing costs continue to decrease.

PMID- 27696622
TI  - Virtue male sling for post-prostatectomy stress incontinence: a prospective
      evaluation and mid-term outcomes.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the Virtue(r) male sling
      (Coloplast, Humlebaek, Denmark) in a cohort of patients affected by post
      prostatectomy stress urinary incontinence (SUI). METHODS: All 29 consecutive
      patients treated with a Virtue male sling at our Institution between July 2012
      and October 2013 were included in the present prospective, non-randomized study.
      Patients were evaluated preoperatively and at 1, 3, 6, 12, 24 and 36 months after
      surgery using a 24-h pad weight test, the International Consultation on
      Incontinence short-form questionnaire (ICIQ-SF), Urinary Symptom Profile (USP)
      questionnaire, a bladder diary, uroflowmetry and the Patient Global Impression of
      Improvement (PGI-I) and Patient Global Impression of Severity questionnaires.
      RESULTS: The mean patient age was 65.5 years. A total of 72.4% of patients had
      preoperative mild incontinence (1-2 pads/day), while nine patients used 3-5
      pads/day. There were a total of 17 complications, which occurred in 29 patients
      (58.6%); all were Clavien-Dindo grade I. At 12-month follow-up patients showed a
      significant improvement in 24-h pad test (128.6 vs 2.5 g), number of pads per day
      (2 vs 0), ICIQ-SF score (14.3 vs 0.9) and USP score for SUI (4 vs 0), and
      outcomes remained stable at 36 months. At last follow-up, the median score on the
      PGI-I questionnaire was 1 (very much better). CONCLUSION: The Virtue male sling
      is an effective treatment option for low to moderate post-prostatectomy
      incontinence.

PMID- 27696623
TI  - Novel insights into the composition and function of the Toxoplasma IMC sutures.
AB  - The Toxoplasma inner membrane complex (IMC) is a specialized organelle underlying
      the parasite's plasma membrane that consists of flattened rectangular membrane
      sacs that are sutured together and positioned atop a supportive cytoskeleton. We
      have previously identified a novel class of proteins localizing to the transverse
      and longitudinal sutures of the IMC, which we named IMC sutures components
      (ISCs). Here, we have used proximity-dependent biotin identification at the
      sutures to better define the composition of this IMC subcompartment. Using ISC4
      as bait, we demonstrate biotin-dependent labeling of the sutures and have
      uncovered two new ISCs. We also identified five new proteins that exclusively
      localize to the transverse sutures that we named transverse sutures components
      (TSCs), demonstrating that components of the IMC sutures consist of two groups:
      those that localize to the transverse and longitudinal sutures (ISCs) and those
      residing only in the transverse sutures (TSCs). In addition, we functionally
      analyze the ISC protein ISC3 and demonstrate that ISC3-null parasites have
      morphological defects and reduced fitness in vitro. Most importantly, Deltaisc3
      parasites exhibit a complete loss of virulence in vivo. These studies expand the
      known composition of the IMC sutures and highlight the contribution of ISCs to
      the ability of the parasite to proliferate and cause disease.

PMID- 27696625
TI  - Maternal zinc deficiency and congenital anomalies in newborns.
AB  - BACKGROUND: Zinc deficiency in pregnant women is common, especially in the third
      trimester of pregnancy. The available data, however, on the association between
      zinc deficiency and congenital malformations in the Iranian population are
      insufficient. The aim of this study was therefore to determine whether maternal
      serum zinc deficiency is associated with major congenital malformations in
      newborns. METHODS: This descriptive, case-control study involved mothers of 80
      neonates with congenital anomalies (study group) admitted to the Mofid Children's
      Hospital, Tehran, Iran. During the same period (2014 and 2015), serum zinc was
      measured in 80 mothers who had delivered normal newborns without congenital
      malformations (control group). RESULTS: Mothers with serum zinc deficiency had a
      more than sevenfold risk of malformations in the fetus compared with mothers with
      normal serum zinc (OR, 7.013; 95%CI: 2.716-18.110). Newborns with malformation
      weighing <=2500 g were associated with lower maternal serum zinc compared with
      the control group (P = 0.006). CONCLUSIONS: There is an association between
      congenital malformation in newborns and maternal zinc deficiency.

PMID- 27696624
TI  - TAK1 maintains the survival of immunoglobulin lambda-chain-positive B cells.
AB  - TAK1 (MAP3K7) mediation of the IkappaB kinase (IKK) complex-nuclear factor-kappaB
      (NF-kappaB) pathway is crucial for the activation of immune response and to
      perpetuate inflammation. Although progress has been made to understand TAK1
      function in the B-cell receptor (BCR) signaling, the physiological roles of TAK1
      in B-cell development, particularly in the bone marrow (BM), remain elusive.
      Previous studies suggested that the IKK complex is required for the development
      of immunoglobulin light chain lambda-positive B cells, but not for receptor
      editing. In contrast, NF-kappaB activity is suggested to be involved in the
      regulation of receptor editing. Thus, NF-kappaB signaling in early B-cell
      development is yet to be fully characterized. Therefore, we addressed the role of
      TAK1 in early B-cell development. TAK1-deficient mice showed significant
      reduction of BM Iglambda-positive B-cell numbers without any alteration in the
      BCR editing. Furthermore, the expression of survival factor Bcl-2 was reduced in
      TAK1-deficient BM B cells as assessed by microarray and quantitative PCR
      analyses. Ex vivo over-expression of exogenous Bcl-2 enhanced the survival of
      TAK1-deficient Iglambda-positive B cells. TAK1-IKK-NF-kappaB signaling
      contributes to the survival of lambda-chain-positive B cells through NF-kappaB
      dependent anti-apoptotic Bcl-2 expression.

PMID- 27696626
TI  - Ubiquitin-proteasome-dependent degradation of TBP-like protein is prevented by
      direct binding of TFIIA.
AB  - Although the majority of gene expression is driven by TATA-binding protein (TBP)
      based transcription machinery, it has been reported that TBP-related factors
      (TRFs) are also involved in the regulation of gene expression. TBP-like protein
      (TLP), which is one of the TRFs and exhibits the highest affinity to TFIIA among
      known proteins, has recently been showed to have significant roles in gene
      regulation. However, how the level of TLP is maintained in vivo has remained
      unknown. In this study, we explored the mechanism by which TLP protein is turned
      over in vivo and the factor that maintains the amount of TLP. We showed that TLP
      is rapidly degraded by the ubiquitin-proteasome system and that tight interaction
      with TFIIA results in protection of TLP from ubiquitin-proteasome-dependent
      degradation. The half-life of TLP was shown to be less than a few hours, and the
      proteasome inhibitor MG132 specifically suppressed TLP degradation. Moreover,
      knockdown and over-expression experiments showed that TFIIA is engaged in
      stabilization of TLPin vivo. Thus, we showed a novel characteristic of TLP, that
      is, interaction with TFIIA is essential to suppress proteasome-dependent turnover
      of TLP, providing a further insight into TLP-governed gene regulation.

PMID- 27696627
TI  - Influenza A virus nucleoprotein targets subnuclear structures.
AB  - The Influenza A virus nucleoprotein (NP) is the major protein component of the
      genomic viral ribonucleoprotein (vRNP) complexes, which are the replication- and
      transcription-competent units of Influenza viruses. Early during infection, NP
      mediates import of vRNPs into the host cell nucleus where viral replication and
      transcription take place; also newly synthesized NP molecules are targeted into
      the nucleus, enabling coreplicational assembly of progeny vRNPs. NP reportedly
      acts as regulatory factor during infection, and it is known to be involved in
      numerous interactions with host cell proteins. Yet, the NP-host cell interplay is
      still poorly understood. Here, we report that NP significantly interacts with the
      nuclear compartment and displays distinct affinities for different subnuclear
      structures. NP subnuclear behavior was studied by expression of fluorescent NP
      fusion proteins - including obligate monomeric NP - and site-specific
      fluorescence photoactivation measurements. We found that NP constructs accumulate
      in subnuclear domains frequently found adjacent to or overlapping with
      promyelocytic leukemia bodies and Cajal bodies. Targeting of NP to Cajal bodies
      could further be demonstrated in the context of virus infection. We hypothesize
      that by targeting functional nuclear organization, NP might either link viral
      replication to specific cellular machinery or interfere with host cell processes.

PMID- 27696628
TI  - Reproducibility of high-definition (3D) manometry and its agreement with high
      resolution (2D) manometry in women with fecal incontinence.
AB  - BACKGROUND: While widely used in clinical practice, the reproducibility of high
      definition anorectal manometry (HD-ARM) remains unclear. We evaluated the intra
      individual reproducibility of HD-ARM and compared pressures measured with HD-ARM
      and high-resolution anorectal manometry (HR-ARM). METHODS: Thirty-six women with
      fecal incontinence had an initial HD-ARM (HD-ARM1); on the same day, after
      randomization, 21 had a second (HD-ARM2). Sixteen women had a third (HD-ARM3) 4
      weeks later. Twenty-five had also been evaluated by HR-ARM previously. Rectoanal
      pressures were assessed at rest, during squeeze and simulated evacuation.
      Concordance among pressures was assessed with Lin's concordance correlation
      coefficient (CCC). KEY RESULTS: Anal resting and squeeze pressures measured with
      HD-ARM were reproducible on the same and different days; for average resting
      pressures of HD-ARM1 vs HD-ARM2, CCC = 0.73 (95% confidence interval [CI]: 0.53
      0.94), and for HD-ARM1 vs HD-ARM3, CCC = 0.60 (95% CI: 0.28-0.93). For maximum
      squeeze pressures of HD-ARM1 vs HD-ARM2, CCC = 0.86 (95% CI: 0.75-0.97), and for
      HD-ARM1 vs HD-ARM3, CCC = 0.56 (95% CI: 0.21-0.91). The rectoanal gradient during
      evacuation was significantly concordant between HD-ARM1 and HD-ARM2 but not HD
      ARM1 and HD-ARM3. Resting (CCC = 0.38 [95% CI: 0.14-0.62]) and squeeze pressures
      (CCC = 0.73 [95% CI: 0.57-0.89]) measured with HD-ARM1 and HR-ARM were also
      concordant. CONCLUSIONS & INFERENCES: Among women with fecal incontinence,
      measurements with HD-ARM were reproducible on the same (anal resting and squeeze
      pressures and rectoanal gradient during evacuation) and different days (anal
      resting and squeeze pressures) and correlated with HR-ARM measurements. These
      findings support use of HD-ARM and HR-ARM for longitudinal assessments of anal
      resting and squeeze pressures.

PMID- 27696629
TI  - Association between HIV infection and socio-economic status: evidence from a
      semirural area of southern Mozambique.
AB  - OBJECTIVES: To analyse the association between socio-economic status (SES) and
      HIV in Manhica, a district of Southern Mozambique with one of the highest HIV
      prevalences in the world. METHODS: Data were gathered from two cross-sectional
      surveys performed in 2010 and 2012 among 1511 adults and from the household
      census of the district's population. Fractional polynomial logit models were used
      to analyse the association between HIV and SES, controlling for age and sex and
      taking into account the nonlinearity of covariates. The inequality of the
      distribution of HIV infection with regard to SES was computed through a
      concentration index. RESULTS: Fourth and fifth wealth quintiles, the least poor,
      were associated with a reduced probability of HIV infection compared to the first
      quintile (OR = 0.595, P-value = 0.009 and OR = 0.474, P-value < 0.001,
      respectively). Probability of HIV infection peaked at 36 years and then fell, and
      was always higher for women regardless of age and SES. HIV infection was
      unequally distributed across the SES strata. CONCLUSIONS: Despite the high HIV
      prevalence across the entire population of Manhica, the poorest are at greatest
      risk of being HIV infected. While women have a higher probability of being HIV
      positive than men, both sexes showed the same infection reduction at higher
      levels of SES. HIV interventions in the area should particularly focus on the
      poorest and on women without neglecting anyone else, as the HIV risk is high for
      everyone.

PMID- 27696630
TI  - Extracorporeal membrane oxygenation in 61 neonates: Single-center experience.
AB  - BACKGROUND: There have been few reports on the outcome of extracorporeal membrane
      oxygenation (ECMO) in newborn Japanese infants. METHODS: A review was carried out
      of 61 neonates with ECMO between January 1995 and December 2015 at a single
      center. ECMO was used in neonates with oxygenation index >20 after conventional
      treatment. Background factors, such as etiology, vascular access mode (veno
      venous [VV] or veno-arterial [VA]), number of days with ECMO, and early ECMO
      (within 24 h after birth), were analyzed in relation to outcome with respect to
      survival to hospital discharge (SHD). RESULTS: Survival to hospital discharge was
      achieved in 35 infants (57%), while the remaining 26 died during hospital stay.
      Gestational age at birth was significantly higher and number of days with ECMO
      was significantly lower in SHD infants compared with those with adverse outcome
      (median, 4.0 vs 5.5 days, respectively; P = 0.008). The SHD rate was
      significantly higher for those with VV than VA vascular access mode (78%, 18/23
      vs 45%, 17/38, respectively; P = 0.016), and for those with than without early
      ECMO (72%, 28/39 vs 32%, 7/22, respectively; P = 0.003). The SHD rate was
      relatively high in neonates with meconium aspiration syndrome (86%, 12/14),
      persistent pulmonary hypertension associated with hypoxic ischemic encephalopathy
      (75%, 6/8), and emphysema (80%, 4/5). On stepwise logistic regression analysis
      two independent factors of SHD were identified: early ECMO (OR, 9.63; 95%CI: 2.47
      37.6) and ECMO length <8 days (OR, 8.05; 95%CI: 1.94-33.5). CONCLUSIONS: Neonates
      with early ECMO and those with ECMO duration <8 days may benefit from ECMO with
      respect to SHD.

PMID- 27696631
TI  - Persistence of a dominant bovine lineage of group B Streptococcus reveals genomic
      signatures of host adaptation.
AB  - Group B Streptococcus (GBS) is a host-generalist species, most notably causing
      disease in humans and cattle. However, the differential adaptation of GBS to its
      two main hosts, and the risk of animal to human infection remain poorly
      understood. Despite improvements in control measures across Europe, GBS is still
      one of the main causative agents of bovine mastitis in Portugal. Here, by whole
      genome analysis of 150 bovine GBS isolates we discovered that a single CC61 clone
      is spreading throughout Portuguese herds since at least the early 1990s, having
      virtually replaced the previous GBS population. Mutations within an
      iron/manganese transporter were independently acquired by all of the CC61
      isolates, underlining a key adaptive strategy to persist in the bovine host.
      Lateral transfer of bacteriocin production and antibiotic resistance genes also
      underscored the contribution of the microbial ecology and genetic pool within the
      bovine udder environment to the success of this clone. Compared to strains of
      human origin, GBS evolves twice as fast in bovines and undergoes recurrent
      pseudogenizations of human-adapted traits. Our work provides new insights into
      the potentially irreversible adaptation of GBS to the bovine environment.

PMID- 27696632
TI  - Ground transport stress affects bacteria in the rumen of beef cattle: A real-time
      PCR analysis.
AB  - Transport stress syndrome often appears in beef cattle during ground
      transportation, leading to changes in their capacity to digest food due to
      changes in rumen microbiota. The present study aimed to analyze bacteria before
      and after cattle transport. Eight Xianan beef cattle were transported over 1000
      km. Rumen fluid and blood were sampled before and after transport. Real-time PCR
      was used to quantify rumen bacteria. Cortisol and adrenocorticotrophic hormone
      (ACTH) were measured. Cortisol and ACTH were increased on day 1 after
      transportation and decreased by day 3. Cellulolytic bacteria (Fibrobacter
      succinogenes and Ruminococcus flavefaciens), Ruminococcus amylophilus and
      Prevotella albensis were increased at 6 h and declined by 15 days after
      transport. There was a significant reduction in Succinivibrio dextrinosolvens,
      Prevotella bryantii, Prevotella ruminicola and Anaerovibrio lipolytica after
      transport. Rumen concentration of acetic acid increased after transport, while
      rumen pH and concentrations of propionic and butyric acids were decreased. Body
      weight decreased by 3 days and increased by 15 days after transportation. Using
      real-time PCR analysis, we detected changes in bacteria in the rumen of beef
      cattle after transport, which might affect the growth of cattle after transport.

PMID- 27696633
TI  - Chiropractic spinal manipulative therapy for migraine: a three-armed, single
      blinded, placebo, randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: To investigate the efficacy of chiropractic spinal
      manipulative therapy (CSMT) for migraineurs. METHODS: This was a prospective
      three-armed, single-blinded, placebo, randomized controlled trial (RCT) of 17
      months duration including 104 migraineurs with at least one migraine attack per
      month. The RCT was conducted at Akershus University Hospital, Oslo, Norway.
      Active treatment consisted of CSMT, whereas placebo was a sham push manoeuvre of
      the lateral edge of the scapula and/or the gluteal region. The control group
      continued their usual pharmacological management. The RCT consisted of a 1-month
      run-in, 3 months intervention and outcome measures at the end of the intervention
      and at 3, 6 and 12 months follow-up. The primary end-point was the number of
      migraine days per month, whereas secondary end-points were migraine duration,
      migraine intensity and headache index, and medicine consumption. RESULTS:
      Migraine days were significantly reduced within all three groups from baseline to
      post-treatment (P < 0.001). The effect continued in the CSMT and placebo group at
      all follow-up time points, whereas the control group returned to baseline. The
      reduction in migraine days was not significantly different between the groups (P
      > 0.025 for interaction). Migraine duration and headache index were reduced
      significantly more in the CSMT than the control group towards the end of follow
      up (P = 0.02 and P = 0.04 for interaction, respectively). Adverse events were
      few, mild and transient. Blinding was strongly sustained throughout the RCT.
      CONCLUSIONS: It is possible to conduct a manual-therapy RCT with concealed
      placebo. The effect of CSMT observed in our study is probably due to a placebo
      response.

PMID- 27696634
TI  - Physical activity and lung function decline in adults with asthma: The HUNT
      Study.
AB  - BACKGROUND AND OBJECTIVE: People with asthma may seek advice about physical
      activity. However, the benefits of leisure time physical activity on lung
      function are unclear. We investigated the association between leisure time
      physical activity and lung function decline in adults with asthma. METHODS: In a
      population-based cohort study in Norway, we used multiple linear regressions to
      estimate the annual mean decline in lung function (and 95% CI) in 1329 people
      with asthma over a mean follow-up of 11.6 years. The durations of light and hard
      physical activity per week in the last year were collected by questionnaire.
      Inactive participants did not report any light or hard activity, while active
      participants reported light or hard activity. RESULTS: The mean decline in forced
      expiratory volume in 1 s (FEV1 ) was 37 mL/year among inactive participants and
      32 mL/year in active participants (difference: -5 mL/year (95% CI: -13 to 3)).
      The mean decline in forced vital capacity (FVC) was 33 mL/year among inactive
      participants and 31 mL/year in active participants (difference: -2 mL/year (95%
      CI: -11 to 7)). The mean decline in FEV1 /FVC ratio was 0.36%/year among inactive
      participants and 0.22%/year in active participants (difference: -0.14%/year (95%
      CI: -0.27 to -0.01)). The mean decline in peak expiratory flow (PEF) was 14
      mL/year among the inactive participants and 10 mL/year in active participants
      (difference: -4 mL/year (95% CI: -9 to 1)). CONCLUSION: We observed slightly less
      decline in lung function in physically active than inactive participants with
      asthma, particularly for FEV1 , FEV1 /FVC ratio and PEF.

PMID- 27696635
TI  - Antiretroviral therapy status among people who died of AIDS-related causes from
      2009 to 2013 in Brazil: a population-based study.
AB  - OBJECTIVE: To describe the antiretroviral therapy status of people living with
      HIV (PLHIV) who died of AIDS-related causes between 2009 and 2013. METHODS: We
      conducted a cross-sectional, population-based study. Data were obtained by
      linking the mortality information system and the national ART dispensing
      database. Trends were modelled using linear regression analysis. RESULTS: A total
      of 61 425 AIDS-related deaths were registered in Brazil between 2009 and 2013.
      Median age at death was 41 years (IQR: 33-49), and 65.7% (40 337) of deaths were
      among men; 47.2% (29 004) of PLHIV who died during the study period had never
      started treatment, 7.0% (4274) had discontinued it, 15.9% (9775) were on ART for
      6 months or less and 29.9% (18 372) were on ART for more than 6 months. Only 1.3%
      of PLHIV were on third-line ARV regimens when they died. CONCLUSIONS: AIDS
      related mortality remains a challenge even in a context of sustained universal
      access to antiretroviral treatment due to failure of service provision, not to
      therapy failure. Robust health policies closing gaps in the HIV continuum of care
      are crucial to further reduce mortality.

PMID- 27696636
TI  - Intracellular amorphous carbonates uncover a new biomineralization process in
      eukaryotes.
AB  - Until now, descriptions of intracellular biomineralization of amorphous
      inclusions involving alkaline-earth metal (AEM) carbonates other than calcium
      have been confined exclusively to cyanobacteria (Couradeau et al., 2012). Here,
      we report the first evidence of the presence of intracellular amorphous granules
      of AEM carbonates (calcium, strontium, and barium) in unicellular eukaryotes.
      These inclusions, which we have named micropearls, show concentric and
      oscillatory zoning on a nanometric scale. They are widespread in certain
      eukaryote phytoplankters of Lake Geneva (Switzerland) and represent a previously
      unknown type of non-skeletal biomineralization, revealing an unexpected pathway
      in the geochemical cycle of AEMs. We have identified Tetraselmis cf. cordiformis
      (Chlorophyta, Prasinophyceae) as being responsible for the formation of one
      micropearl type containing strontium ([Ca,Sr]CO3 ), which we also found in a
      cultured strain of Tetraselmis cordiformis. A different flagellated eukaryotic
      cell forms barium-rich micropearls [(Ca,Ba)CO3 ]. The strontium and barium
      concentrations of both micropearl types are extremely high compared with the
      undersaturated water of Lake Geneva (the Ba/Ca ratio of the micropearls is up to
      800,000 times higher than in the water). This can only be explained by a high
      biological pre-concentration of these elements. The particular characteristics of
      the micropearls, along with the presence of organic sulfur-containing compounds
      associated with and surrounding the micropearls-strongly suggest the existence of
      a yet-unreported intracellular biomineralization pathway in eukaryotic micro
      organisms.

PMID- 27696638
TI  - Comparing performance of 30-day readmission risk classifiers among hospitalized
      primary care patients.
AB  - RATIONALE, AIMS AND OBJECTIVES: Hospital readmission within 30 days of discharge
      occurs in almost 20% of US Medicare patients and may be a marker of poor quality
      inpatient care, ineffective hospital to home transitions, or disease severity.
      Within a patient centered medical home, care transition interventions may only be
      practical from cost and staffing perspectives if targeted at patients with the
      greatest risk of readmission. Various scoring algorithms attempt to predict
      patients at risk for 30-day readmission, but head-to-head comparison of
      performance is lacking. Compare published scoring algorithms which use generally
      available electronic medical record data on the same set of hospitalized primary
      care patients. METHODS: The LACE index, the LACE+ index, the HOSPITAL score, and
      the readmission risk score were computed on a consecutive cohort of 26,278
      hospital admissions. Classifier performance was assessed by plotting receiver
      operating characteristic curves comparing the computed score with the actual
      outcome of death or readmission within 30 days. Statistical significance of
      differences in performance was assessed using bootstrapping techniques. RESULTS:
      Correct readmission classification on this cohort was moderate with the following
      c-statistics: Readmission risk score 0.666; LACE 0.680; LACE+ 0.662; and HOSPITAL
      0.675. There was no statistically significant difference in performance between
      classifiers. CONCLUSIONS: Logistic regression based classifiers yield only
      moderate performance when utilized to predict 30-day readmissions. The task is
      difficult due to the variety of underlying causes for readmission, nonlinearity,
      and the arbitrary time period of concern. More sophisticated classification
      techniques may be necessary to increase performance and allow patient centered
      medical homes to effectively focus efforts to reduce readmissions.

PMID- 27696637
TI  - MiR-133b inhibits growth of human gastric cancer cells by silencing pyruvate
      kinase muscle-splicer polypyrimidine tract-binding protein 1.
AB  - The metabolism in tumor cells shifts from oxidative phosphorylation to glycolysis
      even in an aerobic environment. This phenomenon is known as the Warburg effect.
      This effect is regulated mainly by polypyrimidine tract-binding protein 1
      (PTBP1), which is a splicer of the mRNA for the rate-limiting enzymes of
      glycolysis, pyruvate kinase muscle 1 and 2 (PKM1 and PKM2). In the present study,
      we demonstrated that miR-133b reduced PTBP1 expression at translational level and
      that the expression levels of miR-133b were significantly downregulated in
      gastric cancer clinical samples and human cell lines, whereas the protein
      expression level of PTBP1 was upregulated in 80% of the 20 clinical samples of
      gastric cancer examined. Ectopic expression of miR-133b and knockdown of PTBP1 in
      gastric cancer cells inhibited cell proliferation through the induction of
      autophagy by the switching of PKM isoform expression from PKM2-dominant to PKM1
      dominant. The growth inhibition was partially canceled by an autophagy inhibitor
      3-MA or a reactive oxygen species scavenger N-acetylcysteine. These findings
      indicated that miR-133b acted as a tumor-suppressor through negative regulation
      of the Warburg effect in gastric cancer cells.

PMID- 27696639
TI  - Label-free identification of antibiotic resistant isolates of living Escherichia
      coli: Pilot study.
AB  - We introduce a label-free spectroscopic method to classify subtypes of quinolone
      nonsusceptible Escherichia coli (E. coli) isolates obtained from human blood
      cultures. Raman spectroscopy with a 30-nm gold-deposited, surface-enhanced Raman
      scattering (SERS) substrate was used to evaluate three multilocus sequencing
      typing (MLST)-predefined groups including E. coli ATCC25922, E. coli ST131:O75,
      and E. coli ST1193:O25b. Although there was a coffee-ring effect, the ring zone
      was selected at the ideal position to screen E. coli isolates. Strong Raman peaks
      were present at 1001-1004 cm-1 (C?C aromatic ring breathing stretching
      vibrational mode of phenylalanine), 1447-1448 cm-1 (C?H2 scissoring deformation
      vibrational mode), and 1667 cm-1 (amide I alpha-helix). Although the three MLST
      predefined E. coli isolates had similar Raman spectral patterns, a support vector
      machine (SVM) learning algorithm-assisted principal component analysis (PCA)
      analysis had superior performance in detecting the presence of quinolone
      nonsusceptible E. coli isolates as well as classifying similar microbes, such as
      quinolone-nonsusceptible E. coli ST131:O75 and E. coli ST1193:O25b isolates.
      Therefore, this label-free and nondestructive technique is likely to be useful
      for clinically diagnosing quinolone-nonsusceptible E. coli isolates with the MLST
      method.

PMID- 27696640
TI  - Assessing the multiscale architecture of muscular tissue with Q-space magnetic
      resonance imaging: Review.
AB  - Contraction of muscular tissue requires the synchronized shortening of myofibers
      arrayed in complex geometrical patterns. Imaging such myofiber patterns with
      diffusion-weighted MRI reveals architectural ensembles that underlie force
      generation at the organ scale. Restricted proton diffusion is a stochastic
      process resulting from random translational motion that may be used to probe the
      directionality of myofibers in whole tissue. During diffusion-weighted MRI,
      magnetic field gradients are applied to determine the directional dependence of
      proton diffusion through the analysis of a diffusional probability distribution
      function (PDF). The directions of principal (maximal) diffusion within the PDF
      are associated with similarly aligned diffusion maxima in adjacent voxels to
      derive multivoxel tracts. Diffusion-weighted MRI with tractography thus
      constitutes a multiscale method for depicting patterns of cellular organization
      within biological tissues. We provide in this review, details of the method by
      which generalized Q-space imaging is used to interrogate multidimensional
      diffusion space, and thereby to infer the organization of muscular tissue. Q
      space imaging derives the lowest possible angular separation of diffusion maxima
      by optimizing the conditions by which magnetic field gradients are applied to a
      given tissue. To illustrate, we present the methods and applications associated
      with Q-space imaging of the multiscale myoarchitecture associated with the human
      and rodent tongues. These representations emphasize the intricate and continuous
      nature of muscle fiber organization and suggest a method to depict structural
      "blueprints" for skeletal and cardiac muscle tissue.

PMID- 27696641
TI  - A social-technological epistemology of clinical decision-making as mediated by
      imaging.
AB  - In recent years there has been growing attention to the epistemology of clinical
      decision-making, but most studies have taken the individual physicians as the
      central object of analysis. In this paper we argue that knowing in current
      medical practice has an inherently social character and that imaging plays a
      mediating role in these practices. We have analyzed clinical decision-making
      within a medical expert team involved in diagnosis and treatment of patients with
      pulmonary hypertension (PH), a rare disease requiring multidisciplinary team
      involvement in diagnosis and management. Within our field study, we conducted
      observations, interviews, video tasks, and a panel discussion. Decision-making in
      the PH clinic involves combining evidence from heterogeneous sources into a
      cohesive framing of a patient, in which interpretations of the different sources
      can be made consistent with each other. Because pieces of evidence are generated
      by people with different expertise and interpretation and adjustments take place
      in interaction between different experts, we argue that this process is socially
      distributed. Multidisciplinary team meetings are an important place where
      information is shared, discussed, interpreted, and adjusted, allowing for a
      collective way of seeing and a shared language to be developed. We demonstrate
      this with an example of image processing in the PH service, an instance in which
      knowledge is distributed over multiple people who play a crucial role in
      generating an evaluation of right heart function. Finally, we argue that images
      fulfill a mediating role in distributed knowing in 3 ways: first, as enablers or
      tools in acquiring information; second, as communication facilitators; and third,
      as pervasively framing the epistemic domain. With this study of clinical decision
      making in diagnosis and treatment of PH, we have shown that clinical decision
      making is highly social and mediated by technologies. The epistemology of
      clinical decision-making needs to take social and technological mediation into
      account.

PMID- 27696643
TI  - Genomic diversification of marine cyanophages into stable ecotypes.
AB  - Understanding the structure and origin of natural bacteriophage genomic diversity
      is important in elucidating how bacteriophages influence the mortality rates and
      composition of their host communities. Here, we examine the genetic structure and
      genomic diversification of naturally occurring bacteriophages by analyzing the
      full genomic sequences of over 100 isolates of Synechococcus-infecting
      cyanophages collected over 15 years from coastal waters of Southern New England,
      USA. Our analysis revealed well-supported cyanophage genomic clusters (genome
      wide average nucleotide identity (ANI) >93%) and subclusters (genome-wide ANI
      >98%) that remained consistent for a decade or longer. Furthermore, by combining
      the genomic data with genetic analysis of an additional 800 isolates and
      environmental amplicon sequence data both genomic clusters and subclusters were
      found to exhibit clear temporal and/or spatial patterns of abundance, suggesting
      that these units represent distinct viral ecotypes. The processes responsible for
      diversification of cyanophages into genomic clusters and subclusters were similar
      across genetic scales and included allelic exchange as well as gene gain and
      loss. Isolates belonging to different subclusters were found to differ in genes
      that encoded auxiliary metabolic functions, restriction modification enzymes, and
      virion structural proteins, although the specific traits and selection pressures
      responsible for the maintenance of distinct ecotypes remain unknown.

PMID- 27696642
TI  - Partially methylated alleles, microdeletion, and tissue mosaicism in a fragile X
      male with tremor and ataxia at 30 years of age: A case report.
AB  - CGG repeat expansion >200 within FMR1, termed full mutation (FM), has been
      associated with promoter methylation, consequent silencing of gene expression and
      fragile X syndrome (FXS)-a common cause of intellectual disability and co-morbid
      autism. Unmethylated premutation (55-199 repeats) and FM alleles have been
      associated with fragile X related tremor/ataxia syndrome (FXTAS), a late onset
      neurodegenerative disorder. Here we present a 33-year-old male with FXS, with
      white matter changes and progressive deterioration in gait with cerebellar signs
      consistent with probable FXTAS; there was no evidence of any other cerebellar
      pathology. We show that he has tissue mosaicism in blood, saliva, and buccal
      samples for the size and methylation of his expanded alleles and a de novo,
      unmethylated microdeletion. This microdeletion involves a ~80 bp sequence in the
      FMR1 promoter as well as complete loss of the CGG repeat in a proportion of
      cells. Despite FMR1 mRNA levels in blood within the normal range, the methylation
      and CGG sizing results are consistent with the diagnosis of concurrent FXS and
      probable FXTAS. The demonstrated presence of unmethylated FM alleles would
      explain the manifestation of milder than expected cognitive and behavioral
      impairments and early onset of cerebellar ataxia. Our case suggests that
      individuals with FXS, who manifest symptoms of FXTAS, may benefit from more
      detailed laboratory testing. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696644
TI  - ACMHN's 42nd International Mental Health Nursing Conference Nurses striving to
      tackle disparity in health care 25 - 27 October 2016, Adelaide Convention Centre.

PMID- 27696645
TI  - Sensitivity of Fusarium culmorum to triazoles: impact of trichothecene
      chemotypes, oxidative stress response and genetic diversity.
AB  - BACKGROUND: Fusarium culmorum is a fungal pathogen occurring worldwide on various
      weeds and important crops. Triazoles have been shown to be the most effective
      fungicide for managing Fusarium spp., but little is known about their specific
      activity on F. culmorum. RESULTS: The sensitivity of 107 F. culmorum strains to
      triazoles was assessed using microtitre plate assays. The EC50 values ranged from
      0.14 to 1.53 mg L-1 for tebuconazole and from 0.25 to 2.47 mg L-1 for
      epoxiconazole. Cross-resistance to both azoles was found (r = 0.61). F. culmorum
      appeared to be significantly more sensitive than F. graminearum or F. cerealis.
      No increase in the mean EC50 was observed over time, which might be related to an
      unfavourable fitness cost, measured here as fungal growth. On average, nivalenol
      producing strains of F. culmorum were significantly more resistant than
      deoxynivalenol-producing strains. The relationship between resistance and
      chemotype-dependent adaptation to oxidative stress was investigated, but remained
      unclear. No link between inter-simple sequence repeat (ISSR) genetic diversity
      and triazole resistance could be established. CONCLUSION: Fungicide use might not
      be a driving force in the evolution of F. culmorum, and the benefit of a
      resistance trait probably does not outweigh its costs. (c) 2016 Society of
      Chemical Industry.

PMID- 27696646
TI  - Diet-induced changes of redox potential underlie compositional shifts in the
      rumen archaeal community.
AB  - Dietary changes are known to affect gut community structure, but questions remain
      about the mechanisms by which diet induces shifts in microbiome membership. Here,
      we addressed these questions in the rumen microbiome ecosystem - a complex
      microbial community that resides in the upper digestive tract of ruminant animals
      and is responsible for the degradation of the ingested plant material. Our
      dietary intervention experiments revealed that diet affects the most abundant
      taxa within the microbiome and that a specific group of methanogenic archaea of
      the order Methanomicrobiales is highly sensitive to its changes. Using
      metabolomic analyses together with in vitro microbiology approaches and whole
      genome sequencing of Methanomicrobium mobile, a key species within this group, we
      identified that redox potential changes with diet and is the main factor that
      causes these dietary induced alternations in this taxa's abundance. Our genomic
      analysis suggests that the redox potential effect stems from a reduced number of
      anti-reactive oxygen species proteins coded in this taxon's genome. Our study
      highlights redox potential as a pivotal factor that could serve as a sculpturing
      force of community assembly within anaerobic gut microbial communities.

PMID- 27696647
TI  - Ecological and genetic determinants of plasmid distribution in Escherichia coli.
AB  - Bacterial plasmids are important carriers of virulence and antibiotic resistance
      genes. Nevertheless, little is known of the determinants of plasmid distribution
      in bacterial populations. Here the factors affecting the diversity and
      distribution of the large plasmids of Escherichia coli were explored in cattle
      grazing on semi-natural grassland, a set of populations with low frequencies of
      antibiotic resistance genes. Critically, the population genetic structure of
      bacterial hosts was chararacterized. This revealed structured E. coli populations
      with high diversity between sites and individuals but low diversity within cattle
      hosts. Plasmid profiles, however, varied considerably within the same E. coli
      genotype. Both ecological and genetic factors affected plasmid distribution:
      plasmid profiles were affected by site, E. coli diversity, E. coli genotype and
      the presence of other large plasmids. Notably 3/26 E. coli serotypes accounted
      for half the observed plasmid-free isolates indicating that within species
      variation can substantially affect carriage of the major conjugative plasmids.
      The observed population structure suggest that most of the opportunities for
      within species plasmid transfer occur between different individuals of the same
      genotype and support recent experimental work indicating that plasmid-host
      coevolution, and epistatic interactions on fitness costs are likely to be
      important in determining occupancy.

PMID- 27696649
TI  - Functional analysis of Escherichia coli Yad fimbriae reveals their potential role
      in environmental persistence.
AB  - Initial adhesion of bacterial cells to surfaces or host tissues is a key step in
      colonisation and biofilm formation processes, and is mediated by cell surface
      appendages. It was previously demonstrated that Escherichia coli K-12 possesses
      an arsenal of silenced chaperone-usher fimbriae that were functional when
      constitutively expressed. Among them, production of prevalent Yad fimbriae
      induces adhesion to abiotic surfaces. Functional characterisation of Yad fimbriae
      were undertook, and YadN was identified as the most abundant and potential major
      pilin, and YadC as the potential tip-protein of Yad fimbriae. It was showed that
      Yad production participates to binding of E. coli K-12 to human eukaryotic cells
      (Caco-2) and inhibits macrophage phagocytosis, but also enhances E. coli K-12
      binding to xylose, a major component of the plant cell wall, through its tip
      lectin YadC. Consistently, it was demonstrated that Yad production provides E.
      coli with a competitive advantage in colonising corn seed rhizospheres. The
      latter phenotype is correlated with induction of Yad expression at temperatures
      below 37 degrees C, and under anaerobic conditions, through a complex regulatory
      network. Taken together, these results suggest that Yad fimbriae are versatile
      adhesins that beyond potential capacities to modulate host-pathogen interactions
      might contribute to E. coli environmental persistence.

PMID- 27696648
TI  - Gastrointestinal histoplasmosis in a patient after autologous stem cell
      transplant for multiple myeloma.
AB  - A 59-year-old patient with multiple myeloma on maintenance chemotherapy presented
      with fever, weight loss, and night sweats. An F-18 fluorodeoxyglucose (FDG)
      positron emission tomography (PET) computed tomography (CT) showed intra
      abdominal lymphadenopathy with a mesenteric mass that led to further workup and
      diagnosis of histoplamosis. The patient was treated with amphotericin B and
      subsequently switched to itraconazole. This exemplifies the usefulness of FDG PET
      CT in diagnosis of infectious complications.

PMID- 27696650
TI  - Transcatheter aortic valve implantation in degenerative sutureless perceval
      aortic bioprosthesis.
AB  - Sutureless aortic bioprostheses (SAB) are increasingly being used to provide
      shorter cross-clamp time. Valve-in-valve transcatheter aortic valve replacement
      (VIV-A) is shown to be effective and safe in the vast majority of patients with
      degenerated bioprosthetics, yet its' use in SAB failure is infrequent. We present
      a case of balloon-expandable VIV-A in an 80-year-old woman who suffered severe
      symptomatic aortic regurgitation in a failed Perceval S 21-mm valve. Computed
      tomography scan demonstrated a deformed valve. Our heart team favored a
      percutaneous VIV-A over reoperation due to the patients' high surgical risk. An
      Edwards-Sapien XT 23 mm was successfully deployed with excellent results. The
      patient remained asymptomatic following 6 months. As other bioprosthesis, some
      sutureless valves are condemned to structural valve degeneration. Because VIV-A
      is being established for managing degenerative bioprosthesis in high risk
      patients, it is cardinal to identify its role in novel degenerative sutureless
      valves. SAB were introduced to the clinical market only 5-7 years ago. The
      absence of sutures may theoretically impose risk for valve instability when
      adding a transcatheter sutureless valve inside the first one. Our successful
      experience was very reassuring. We report its feasibility because we believe it
      should provide support for further investigation on VIV-A within novel SAV. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27696652
TI  - Urinary collecting system invasion is associated with poor survival in patients
      with clear-cell renal cell carcinoma.
AB  - OBJECTIVES: To evaluate the prognostic significance of urinary collecting system
      invasion (UCSI) in a large series of patients with clear-cell renal cell
      carcinoma (RCC). MATERIALS AND METHODS: Patients with clear-cell RCC treated with
      nephrectomy between 2001 and 2010 were reviewed from a prospectively maintained
      registry. One urological pathologist re-reviewed all slides. Cancer-specific
      survival was estimated using the Kaplan-Meier method, and associations of UCSI
      with death from RCC were evaluated using Cox models. RESULTS: Of the 859 patients
      with clear-cell RCC, 58 (6.8%) had UCSI. At last follow-up, 310 patients had died
      from RCC at a median of 1.8 years after surgery. The median follow-up for
      patients alive at last follow-up was 8.2 years. The estimated cancer-specific
      survival at 10 years after surgery for patients with UCSI was 17%, compared with
      60% for patients without UCSI (P < 0.001). In a multivariable model, UCSI
      remained independently associated with an increased risk of death from RCC
      (hazard ratio 1.5; P = 0.018). Further, among patients with pT3 RCC, those with
      USCI had survival outcomes similar to those of patients with pT4 RCC.
      CONCLUSIONS: Collecting system invasion is associated with poor prognosis among
      patients with clear-cell RCC. If validated, consideration should be given to
      including UCSI in future staging systems.

PMID- 27696653
TI  - Virology analyses of HCV genotype 4 isolates from patients treated with
      simeprevir and peginterferon/ribavirin in the Phase III RESTORE study.
AB  - Simeprevir is a hepatitis C virus NS3/4A protease inhibitor. Hepatitis C virus
      baseline NS3/4A polymorphisms and emerging mutations were characterized in
      treatment-naive and treatment-experienced genotype 4-infected patients treated
      with simeprevir+peginterferon/ribavirin in the RESTORE study. Population
      sequencing of the NS3/4A region was performed and in vitro simeprevir activity
      against site-directed mutants or chimeric replicons with patient-derived NS3
      protease sequences was assessed in a transient replicon assay. Simeprevir
      remained active against most (83/91 [91%]) baseline isolates tested in the
      chimeric replicon assay. Eight baseline isolates reduced simeprevir activity;
      these carried I132L or D168E substitutions reducing simeprevir median activity by
      4.6- and 39-fold, respectively. Six of these eight isolates were from patients
      achieving sustained virologic response. Baseline NS3 Q80K polymorphism was not
      observed in the genotype 4-infected patients. Of the 107 simeprevir-treated
      patients, 37 did not achieve sustained virologic response for any reason. Of the
      32 patients who failed treatment and had sequencing information, 28 (88%) had
      emerging mutations at NS3 positions 80, 122, 155, 156 and/or 168 at time of
      failure, similar to those in genotype 1. Emerging mutations were mainly D168V and
      D168E alone or combined with mutations at position 80. In general, isolates
      obtained at time of failure displayed high-level in vitro resistance to
      simeprevir (fold change >=50) in a chimeric replicon assay with a median
      simeprevir fold change value of 440, consistent with observed mutations. In
      conclusion, emerging mutations in genotype 4 patients failing
      simeprevir+peginterferon/ribavirin treatment were similar to those in genotype 1
      and conferred high-level resistance to simeprevir.

PMID- 27696651
TI  - An evolutionary balance: conservation vs innovation in ciliate membrane
      trafficking.
AB  - As most of eukaryotic diversity lies in single-celled protists, they represent
      unique opportunities to ask questions about the balance of conservation and
      innovation in cell biological features. Among free-living protists the ciliates
      offer ease of culturing, a rich array of experimental approaches, and versatile
      molecular tools, particularly in Tetrahymena thermophila and Paramecium
      tetraurelia. These attributes have been exploited by researchers to analyze a
      wealth of cellular structures in these large and complex cells. This mini-review
      focuses on 3 aspects of ciliate membrane dynamics, all linked with endolysosomal
      trafficking. First is nutrition based on phagocytosis and maturation of food
      vacuoles. Secondly, we discuss regulated exocytosis from vesicles that have
      features of both dense core secretory granules but also lysosome-related
      organelles. The third topic is the targeting, breakdown and resorption of
      parental nuclei in mating partners. For all 3 phenomena, it is clear that
      elements of the canonical membrane-trafficking system have been retained and in
      some cases repurposed. In addition, there is evidence that recently evolved,
      lineage-specific proteins provide determinants in these pathways.

PMID- 27696654
TI  - Cell-specific nitrogen- and carbon-fixation of cyanobacteria in a temperate
      marine system (Baltic Sea).
AB  - We analysed N2 - and carbon (C) fixation in individual cells of Baltic Sea
      cyanobacteria by combining stable isotope incubations with secondary ion mass
      spectrometry (SIMS). Specific growth rates based on N2 - and C-fixation were
      higher for cells of Dolichospermum spp. than for Aphanizomenon sp. and Nodularia
      spumigena. The cyanobacterial biomass, however, was dominated by Aphanizomenon
      sp., which contributed most to total N2 -fixation in surface waters of the
      Northern Baltic Proper. N2 -fixation by Pseudanabaena sp. and colonial
      picocyanobacteria was not detectable. N2 -fixation by Aphanizomenon sp.,
      Dolichospermum spp. and N. spumigena populations summed up to total N2 -fixation,
      thus these genera appeared as sole diazotrophs within the Baltic Sea's euphotic
      zone, while their mean contribution to total C-fixation was 21%. Intriguingly,
      cell-specific N2 -fixation was eightfold higher at a coastal station compared to
      an offshore station, revealing coastal zones as habitats with substantial N2 
      fixation. At the coastal station, the cell-specific C- to N2 -fixation ratio was
      below the cellular C:N ratio, i.e. N2 was assimilated in excess to C-fixation,
      whereas the C- to N2 -fixation ratio exceeded the C:N ratio in offshore sampled
      diazotrophs. Our findings highlight SIMS as a powerful tool not only for
      qualitative but also for quantitative N2 -fixation assays in aquatic
      environments.

PMID- 27696655
TI  - Coprinuslactone protects the edible mushroom Coprinus comatus against biofilm
      infections by blocking both quorum-sensing and MurA.
AB  - Pathogens embedded in biofilms are involved in many infections and are very
      difficult to treat with antibiotics because of higher resistance compared with
      planktonic cells. Therefore, new approaches for their control are urgently
      needed. One way to search for biofilm dispersing compounds is to look at defense
      strategies of organisms exposed to wet environments, which makes them prone to
      biofilm infections. It is reasonable to assume that mushrooms have developed
      mechanisms to control biofilms on their sporocarps (fruiting bodies). A
      preliminary screening for biofilms on sporocarps revealed several species with
      few or no bacteria on their sporocarps. From the edible mushroom Coprinus comatus
      where no bacteria on the sporocarp could be detected (3R,4S)-2-methylene-3,4
      dihydroxypentanoic acid 1,4-lactone, named coprinuslactone, was isolated.
      Coprinuslactone interfered with quorum-sensing and dispersed biofilms of
      Pseudomonas aeruginosa, where it also reduced the formation of the pathogenicity
      factors pyocyanin and rhamnolipid B. Coprinuslactone also damaged Staphylococcus
      aureus cells in biofilms at subtoxic concentrations. Furthermore, it inhibited
      UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), essential for bacterial
      cell wall synthesis. These two modes of action ensure the inhibition of a broad
      spectrum of pathogens on the fruiting body but may also be useful for future
      clinical applications.

PMID- 27696656
TI  - Treatment for childhood acute lymphoblastic leukemia in Taiwan: Taiwan Pediatric
      Oncology Group ALL-2002 study emphasizing optimal reinduction therapy and central
      nervous system preventive therapy without cranial radiation.
AB  - BACKGROUND: Reinduction therapy has improved the outcomes in children with acute
      lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of
      reinduction therapy for standard-risk (SR, or "low-risk" in other groups)
      patients. Also, we evaluated outcomes using triple intrathecal therapy without
      cranial radiation (CrRT) for central nervous system (CNS) preventive therapy.
      PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan
      were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients
      were randomized to receive single or double reinduction courses. The patients
      enrolled before 2009 received CrRT, while those enrolled later did not. The
      Kaplan-Meier method was used to estimate survival rates and the difference
      between two groups was compared by the two-sided log-rank test. RESULTS: In 1,366
      eligible patients, the 5-year overall survival (OS) was 81.6 +/- 1.1% (standard
      error) and 5-year event-free survival (EFS) was 74.3 +/- 1.2%. In SR patients,
      the 5-year OS for one and two reinduction courses was 91.6 +/- 2.1% and 93.7 +/-
      1.8%, respectively, and the 5-year EFS was 85.2 +/- 2.7% and 89.8 +/- 2.3%,
      respectively. There were no significant differences in survival between these two
      groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4
      and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no
      significant difference in CNS relapse or survival between the era with or without
      CrRT. CONCLUSIONS: For SR patients, one-course reinduction was adequate. Triple
      intrathecal therapy alone successfully prevented CNS relapse.

PMID- 27696658
TI  - A qualitative systematic review of maternal infant feeding practices in
      transitioning from milk feeds to family foods.
AB  - Evidence supports the establishment of healthy feeding practices early in life to
      promote lifelong healthy eating patterns protective against chronic disease such
      as obesity. Current early childhood obesity prevention interventions are built on
      extant understandings of how feeding practices relate to infant's cues of hunger
      and satiety. Further insights regarding factors that influence feeding behaviors
      in early life may improve program designs and outcomes. Four electronic databases
      were searched for peer-reviewed qualitative studies published between 2000 to
      2014 with transitional infant feeding practice rationale from developed
      countries. Reporting transparency and potential bias was assessed using the
      Consolidated Criteria for Reporting Qualitative Research quality checklist.
      Thematic synthesis of 23 manuscripts identified three themes (and six sub
      themes): Theme 1. Infant (physical cues and behavioural cues) focuses on the
      perceived signs of readiness to start solids and the feeding to influence growth
      and "health happiness." Theme 2. Mother (coping strategies and knowledge and
      skills) focuses on the early survival of the infant and the family and the
      feeding to satisfy hunger and influence infant contentment, and sleep. Theme 3.
      Community (pressure and inconsistent advice) highlights the importance of
      generational feeding and how conflicting feeding advice led many mothers to adopt
      valued familial or culturally established practices. Overall, mothers were
      pivotal to feeding decisions. Satisfying infant's needs to reach "good mothering"
      status as measured by societal expectations was highly valued but lacked
      consideration of nutrition, obesity, and long term health. Maternal
      interpretation of healthy infant feeding and successful parenting need attention
      when developing strategies to support new families.

PMID- 27696657
TI  - Depressive symptoms modify age effects on hippocampal subfields in older adults.
AB  - AIM: Major depression is associated with hippocampal volume changes, especially
      in late-life depression. These changes usually consist of volume reductions, but
      depression-related increases in hippocampal volume have also been reported.
      Subfield analysis has identified structural changes primarily in the cornu
      ammonis (CA) 1, CA2-3 and subiculum of the hippocampus in individuals with major
      depression; however, it is unclear whether lower levels of depressive symptoms
      are also associated volume reduction, or if depressive symptoms interact with age
      to impact hippocampal subfields. The current study addressed these questions.
      METHODS: A total of 43 community-dwelling older adults completed the Center for
      Epidemiologic Studies Depression Scale and underwent magnetic resonance imaging.
      Hippocampal subfield segmentation was carried out using an automated procedure,
      and left and right volumes from CA1, CA2-3, and the subiculum served as outcome
      measures. Multiple hierarchical regressions were carried out with age, Center for
      Epidemiologic Studies Depression Scale scores and their interaction as the
      independent variables, and sex and total intracranial volume as covariates.
      RESULTS: Higher Center for Epidemiologic Studies Depression Scale scores were
      associated with less age-related volumetric decreases in the right subiculum and
      right CA1. CONCLUSIONS: Age-related atrophy in the hippocampus might be
      counteracted by depressive symptom-related enlargement of CA1 and the subiculum.
      More research is required to better understand the functional significance of
      this relationship. Geriatr Gerontol Int 2017; 17: 1494-1500.

PMID- 27696659
TI  - Transcatheter aortic valve implantation with a Sapien 3 Commander 20 mm valves in
      patients with degenerated 19 mm bioprosthetic aortic valve.
AB  - INTRODUCTION: Transcatheter aortic valve implantation (TAVI) in patients with
      degenerated bioprosthetic aortic valve has been successfully performed as an
      alternative to surgery. We describe our initial experience of valve-in-valve TAVI
      in five patients, using new generation Edwards Sapien 3 transcatheter heart
      valves implanted into degenerated 19 mm bioprosthetic valves. 20-mm Edwards S3
      valves were offered for compassionate use. All patients had significant aortic
      valve stenosis. METHODS AND RESULTS: The main vascular access was achieved and
      pre-closed with two Proglide closure devices in one patient and Prostar closure
      devices in four patients. For each TAVI procedure an Edwards 14 French sheath was
      inserted without complication and sutured in place. The Sapien 3 Commander
      delivery system was inserted and the valve was aligned in the descending aorta.
      The 20-mm Sapien 3 valve was deployed with slow continuous inflation during rapid
      right ventricular pacing. The cranial edge of the Edwards S3 valve was aligned
      with the cranial radiopaque markers of bioprosthesis to minimize paravalvular
      leak. Post-deployment angiography, transesophageal echocardiography and aortogram
      confirmed absence of mild aortic insufficiency and no increase in trans-aortic
      gradient when compared to a naive 19 mm bioprosthetic valve. CONCLUSION: Valve-in
      valve TAVI with the Edwards S3 transcatheter heart valve for degenerative
      bioprosthetic aortic valves is technically feasible. The proper position of the
      stented valve minimizes the risk for post-procedure paravalvular insufficiency
      and provides good transaortic pressure gradient. (c) 2016 Wiley Periodicals, Inc.

PMID- 27696660
TI  - Synthesis and Anticancer Activity of 3-(Substituted Aroyl)-4-(3,4,5
      trimethoxyphenyl)-1H-pyrrole Derivatives.
AB  - A series of 3-(substituted aroyl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole
      derivatives were synthesized and determined for their anticancer activity against
      eleven cancer cell lines and two normal tissue cell lines using MTT assay. Among
      the synthesized compounds, compound 3f was the most potent compound against A375,
      CT-26, HeLa, MGC80-3, NCI-H460 and SGC-7901 cells (IC50  = 8.2 - 31.7 MUm); 3g,
      3n and 3a were the most potent compounds against CHO (IC50  = 8.2 MUm), HCT-15
      (IC50  = 21 MUm) and MCF-7 cells (IC50  = 18.7 MUm), respectively. Importantly,
      all the target compounds showed no cytotoxicity towards the normal tissue cell
      (IC50  > 100 MUm). Thus, these compounds with the potent anticancer activity and
      low toxicity have potential for the development of new anticancer chemotherapy
      agents.

PMID- 27696661
TI  - Criminal Organ Retrieval: Unconscionable.

PMID- 27696662
TI  - Remote Ischemic Conditioning on Recipients of Deceased Renal Transplants Does Not
      Improve Early Graft Function: A Multicenter Randomized, Controlled Clinical
      Trial.
AB  - Delayed graft function is a frequent complication following deceased donor renal
      transplantation, and is closely related to ischemia-reperfusion injury.
      Experimental and clinical studies have shown protection by remote ischemic
      conditioning (RIC). We hypothesized that recipient RIC before kidney graft
      reperfusion reduces the time to graft recovery. This multicenter, blinded,
      randomized, controlled clinical trial included 225 adult recipients of renal
      transplants from deceased donors at four transplantation centers in Denmark,
      Sweden, and the Netherlands. Participants were randomized 1:1 to RIC or sham-RIC.
      RIC consisted of 4 * 5-min thigh occlusion by an inflatable tourniquet each
      followed by 5-min deflation, performed during surgery prior to graft reperfusion.
      The tourniquet remained deflated for sham-RIC. The primary endpoint was the
      estimated time to a 50% decrease in baseline plasma creatinine (tCr50) calculated
      from plasma creatinine measurements 30 days posttransplant or 30 days after the
      last, posttransplant dialysis. No significant differences were observed between
      RIC and sham-RIC-treated patients in the primary outcome median tCr50 (122 h [95%
      confidence interval [CI] 98-151] vs. 112 h [95% CI 91-139], p = 0.58), or the
      number of patients receiving dialysis in the first posttransplant week (33% vs.
      35%, p = 0.71). Recipient RIC does not reduce the time to graft recovery in
      kidney transplantation from deceased donors. ClinicalTrials.gov: NCT01395719.

PMID- 27696663
TI  - Rebuttal: with regards to "angiographic appearance of spontaneous coronary artery
      dissection with intramural hematoma proven on intracoronary imaging".

PMID- 27696664
TI  - A Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome with a KAT6B 10
      base pair palindromic duplication: A recurrent mutation causing a severe
      phenotype mixed with genitopatellar syndrome.
AB  - The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) (MIM#
      603736) and genitopatellar syndrome (GPS) (MIM#606170) are allelic diseases
      caused by KAT6B mutation. Genotype-phenotype correlation is assumed, but a few
      patients manifest overlapping features of both syndromes. Here we report the case
      of a boy with SBBYSS. He had a KAT6B mutation previously reported in typical
      SBBYSS, but he also manifested severe developmental delay, as well as genital
      features and laryngomalacia requiring tracheostomy that conformed to GPS.

PMID- 27696665
TI  - A mechanism for stroke complicating thrombus aspiration.
AB  - We propose a mechanism of how stroke may be caused by thrombus aspiration during
      primary percutaneous coronary intervention (PPCI), and how it may be technique
      dependent. Two recent meta-analyses report increased risk of stroke in patients
      undergoing routine thrombus aspiration during STEMI and the value of this
      technique has been controversial. The mechanism of stroke has not been fully
      explained. This case demonstrates 2 mechanisms by which aspiration might cause
      thrombus embolization. We recommend that if thrombus aspiration is performed
      during PPCI for STEMI, it should be done selectively and carefully. It is prudent
      to make sure the guide catheter tip is not free in the aorta when the aspiration
      catheter is withdrawn, to maintain suction on the aspiration catheter as it is
      withdrawn (particularly if the aspiration port seems to be obstructed), and to
      aspirate the guide catheter after the aspiration catheter is removed to capture
      any fragments of thrombus that remain in the guide catheter. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27696666
TI  - Wnt repertoire and developmental expression patterns in the crustacean
      Thamnocephalus platyurus.
AB  - Wnt genes are a family of conserved glycoprotein ligands that play a role in a
      wide variety of cell and developmental processes, from cell proliferation to axis
      elongation. There are 13 Wnt subfamilies found among metazoans. Eleven of these
      appear conserved in arthropods with a pattern of loss during evolution of as many
      as six subfamilies among hexapods. Here we report on Wnt genes in the branchiopod
      crustacean, Thamnocephalus platyurus, including the first documentation of the
      expression of the complete Wnt gene family in a crustacean. Our results suggest
      fewer Wnt genes were retained in Thamnocephalus than in the related crustacean,
      Daphnia, although the Thamnocephalus Wnt repertoire is larger than that found in
      insects. We also find an intriguing pattern of staggered expression of Wnts-an
      anterior-posterior stagger within the posterior growth zone and a dorsal-ventral
      stagger in the developing segments-suggesting a potential for
      subfunctionalization of Wnts in these regions.

PMID- 27696667
TI  - The anti-ageing hormone klotho induces Nrf2-mediated antioxidant defences in
      human aortic smooth muscle cells.
AB  - Vascular ageing in conditions such as atherosclerosis, diabetes and chronic
      kidney disease, is associated with the activation of the renin angiotensin system
      (RAS) and diminished expression of antioxidant defences mediated by the
      transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). The anti
      ageing hormone klotho promotes longevity and protects against cardiovascular and
      renal diseases. Klotho has been shown to activate Nrf2 and attenuate oxidative
      damage in neuronal cells, however, the mechanisms by which it protects against
      vascular smooth muscle cell VSMC dysfunction elicited by Angiotensin II (AngII)
      remain to be elucidated. AngII contributes to vascular ageing and atherogenesis
      by enhancing VSMC oxidative stress, senescence and apoptosis. This study
      demonstrates that soluble klotho (1 nM, 24 hrs) significantly induces expression
      of Nrf2 and the antioxidant enzymes haeme oxygenase (HO-1) and peroxiredoxin-1
      (Prx-1) and enhances glutathione levels in human aortic smooth muscle cells
      (HASMC). Silencing of Nrf2 attenuated the induction of HO-1 and Prx-1 expression
      by soluble klotho. Furthermore, soluble klotho protected against AngII-mediated
      HASMC apoptosis and senescence via activation of Nrf2. Thus, our findings
      highlight a novel Nrf2-mediated mechanism underlying the protective actions of
      soluble klotho in HAMSC. Targeting klotho may thus represent a therapeutic
      strategy against VSMC dysfunction and cardiovascular ageing.

PMID- 27696668
TI  - The impact of EndoBarrier gastrointestinal liner in obese patients with normal
      glucose tolerance and in patients with type 2 diabetes.
AB  - AIMS: The duodenal-jejunal bypass sleeve ((DJBS) or EndoBarrier Gastrointestinal
      Liner) induces weight loss in obese subjects and may improve glucose homeostasis
      in patients with type 2 diabetes (T2D). To explore the underlying mechanisms, we
      evaluated postprandial physiology including glucose metabolism, gut hormone
      secretion, gallbladder emptying, appetite and food intake in patients undergoing
      DJBS treatment. MATERIAL AND METHODS: A total of 10 normal glucose-tolerant (NGT)
      obese subjects and 9 age-, body weight- and body mass index-matched metformin
      treated T2D patients underwent a liquid mixed meal test and a subsequent ad
      libitum meal test before implantation with DJBS and 1 week (1w) and 26 weeks
      (26w) after implantation. RESULTS: At 26w, both groups had achieved a weight loss
      of 6 to 7 kg. Postprandial glucagon-like peptide-1 (GLP-1) and peptide YY
      responses increased at 1w and 26w, but only in T2D subjects. In contrast, glucose
      dependent insulinotropic polypeptide responses were reduced only by DJBS in the
      NGT group. Postprandial glucose, insulin, C-peptide, glucagon, cholecystokinin
      and gastrin responses were unaffected by DJBS in both groups. Satiety and
      fullness sensations were stronger and food intake was reduced at 1w in NGT
      subjects; no changes in appetite measures or food intake were observed in the T2D
      group. No effect of DJBS on postprandial gallbladder emptying was observed, and
      gastric emptying was not delayed. CONCLUSIONS: DJBS-induced weight loss was
      associated with only marginal changes in postprandial physiology, which may
      explain the absence of effect on postprandial glucose metabolism.

PMID- 27696669
TI  - Mutant analysis by rescue gene excision: New tools for mosaic studies in
      Drosophila.
AB  - A host of classical and molecular genetic tools make Drosophila a tremendous
      model for the dissection of gene activity. In particular, the FLP-FRT technique
      for mitotic recombination has greatly enhanced gene loss-of-function analysis.
      This technique efficiently induces formation of homozygous mutant clones in
      tissues of heterozygous organisms. However, the dependence of the FLP-FRT method
      on cell division, and other constraints, also impose limits on its effectiveness.
      We describe here the generation and testing of tools for Mutant Analysis by
      Rescue Gene Excision (MARGE), an approach whereby mutant cells are formed by loss
      of a rescue transgene in a homozygous mutant organism. Rescue-transgene loss can
      be induced in any tissue or cell-type and at any time during development or in
      the adult using available heat-shock-induced or tissue-specific flippases, or
      combinations of UAS-FLP with Gal4 and Gal80ts reagents. The simultaneous loss of
      a constitutive fluorescence marker (GFP or RFP) identifies the mutant cells. We
      demonstrate the efficacy of the MARGE technique by flip-out (clonal and disc
      wide) of a Ubi-GFP-carrying construct in imaginal discs, and by inducing a known
      yki mutant phenotype in the Drosophila ovary.

PMID- 27696670
TI  - Temporal patterns of induction and recovery of biomarker transcriptional
      responses to 4-Nonylphenol and 17beta-estradiol in the estuarine arrow goby,
      Clevelandia ios.
AB  - Several estuaries along the Pacific Ocean coast of North America were identified
      recently as having elevated 4-nonylphenol (4-NP) in sediments and biota, raising
      concerns about reproductive impacts for wildlife given 4-NP's established
      estrogenic activity as an endocrine-disrupting compound. Here we characterize 4
      NP mediated induction and recovery of estrogen-sensitive gene transcripts in the
      arrow goby (Clevelandia ios), an intertidal fish abundant in estuarine mud flats
      on the west coast of North America. Male gobies were exposed to waterborne 4-NP
      at 10 MUg/L or 100 MUg/L for 20 days followed by a 20 day depuration period.
      Additional males were treated with 17beta-estradiol (E2; 50 ng/L). 4-NP at 100
      MUg/L elevated hepatic mRNAs encoding vitellogenins A (vtgA) and C (vtgC) and
      choriogenin L (chgL) within 72 h, and choriogenin H minor (chgHm) within 12 days.
      Hepatic mRNAs encoding estrogen receptor alpha (esr1) were also elevated after 12
      days of 4-NP exposure, but returned to pre-exposure levels at 20 days even under
      continuing 4-NP treatment. 4-NP did not alter mRNA levels of estrogen receptor
      gamma (esr2a) in the liver, or of esr1, esr2a, and cytochrome P450 aromatase B
      (cyp19a1b) in the brain. The temporal pattern of initial induction for hepatic
      vtgA, vtgC, and chgL transcripts by 4-NP mirrored the pattern by E2, while chgHm
      and esr1 mRNA induction by 4-NP lagged 2-11 days behind the responses of these
      transcripts to E2. These findings establish 4-NP concentration- and time
      dependent induction patterns of choriogenin and vitellogenin transcription
      following exposure to environmentally relevant 4-NP concentrations, while
      concurrently demonstrating tissue-specific induction patterns for esr1 by
      estrogenic compounds. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1513
      1529, 2017.

PMID- 27696671
TI  - Solid-phase microextraction of ultra-trace amounts of tramadol from human urine
      by using a carbon nanotube/flower-shaped zinc oxide hollow fiber.
AB  - A new method is successfully developed for the separation and determination of a
      very low amount of tramadol in urine using functionalized multiwalled carbon
      nanotubes/flower-shaped zinc oxide before solid-phase microextraction combined
      with gas chromatography. Under ultrasonic agitation, a sol of multiwalled carbon
      nanotubes and flower-shaped zinc oxide were forced into and trapped within the
      pore structure of the polypropylene and the sol solution immobilized into the
      hollow fiber. Flower-shaped zinc oxide was synthesized and characterized by
      Fourier transform infrared spectroscopy. The morphology of the fabricated solid
      phase microextraction surface was investigated by scanning electron microscopy
      and X-ray diffraction. The parameters affecting the extraction efficiencies were
      investigated and optimized. Under the optimized conditions, the method shows
      linearity in a wide range of 0.12-7680 ng/mL, and a low detection limit (S/N = 3)
      of 0.03 ng/mL. The precision of the method was determined and a relative standard
      deviation of 3.87% was obtained. This method was successfully applied for the
      separation and determination of tramadol in urine samples. The relative recovery
      percentage obtained for the spiked urine sample at 1000 ng/mL was 94.2%.

PMID- 27696672
TI  - Competitive interactions are mediated in a sex-specific manner by arbuscular
      mycorrhiza in Antennaria dioica.
AB  - Plants usually interact with other plants, and the outcome of such interaction
      ranges from facilitation to competition depending on the identity of the plants,
      including their sexual expression. Arbuscular mycorrhizal (AM) fungi have been
      shown to modify competitive interactions in plants. However, few studies have
      evaluated how AM fungi influence plant intraspecific and interspecific
      interactions in dioecious species. The competitive abilities of female and male
      plants of Antennaria dioica were examined in a greenhouse experiment. Females and
      males were grown in the following competitive settings: (i) without competition,
      (ii) with intrasexual competition, (iii) with intersexual competition, and (iv)
      with interspecific competition by Hieracium pilosella - a plant with similar
      characteristics to A. dioica. Half of the pots were grown with Claroideoglomus
      claroideum, an AM fungus isolated from the same habitat as the plant material. We
      evaluated plant survival, growth, flowering phenology, and production of AM
      fungal structures. Plant survival was unaffected by competition or AM fungi.
      Competition and the presence of AM fungi reduced plant biomass. However, the
      sexes responded differently to the interaction between fungal and competition
      treatments. Both intra- and interspecific competition results were sex-specific,
      and in general, female performance was reduced by AM colonization. Plant
      competition or sex did not affect the intraradical structures, extraradical
      hyphae, or spore production of the AM fungus. These findings suggest that plant
      sexual differences affect fundamental processes such as competitive ability and
      symbiotic relationships with AM fungi.

PMID- 27696673
TI  - Reproducing Optical Properties of Anterior Teeth after Ultra-Conservative
      Preparation.
AB  - OBJECTIVE: Selecting the appropriate material is essential when restoring color
      and appearance of esthetically compromised anterior teeth. CLINICAL
      CONSIDERATIONS: Most of the conventional restorative techniques require tooth
      reduction in order to mimic optical properties of a natural tooth. Fortunately,
      bonding techniques associated with improvements on dental ceramics esthetics
      allow for highly conservative treatment options in which maximum preservation of
      dental tissues can be attained. An analysis of different ceramic materials
      available and different types of tooth preparation is presented in a format of a
      decision tree for treatment planning. CONCLUSIONS: The suggested decision-making
      aims to facilitate clinicians' selection of the most appropriate restorative
      technique for reproducing color and appearance of anterior teeth after ultra
      conservative preparation and according to different clinical scenarios CLINICAL
      SIGNIFICANCE: The selection of the appropriate ceramic material for each case is
      of major importance, since the entire treatment plan will be determined based on
      the type of ceramic material that will be used for the final restoration. Each
      restorative material has a specific tooth preparation requirement, indications,
      and limitations that shall be respected for maximum esthetical outcomes. (J
      Esthet Restor Dent 28:267-276, 2016).

PMID- 27696674
TI  - Clarifying binding difference of ATP and ADP to extracellular signal-regulated
      kinase 2 by using molecular dynamics simulations.
AB  - Extracellular signal-regulated kinase 2 is a promising target for designs and
      development of anticancer drugs. Molecular dynamics simulations and molecular
      mechanics Poisson-Boltzmann method were applied to study binding difference of
      ADP and ATP to extracellular signal-regulated kinase 2. The results prove that
      the binding ability of ATP to extracellular signal-regulated kinase 2 is stronger
      than that of ADP. Principal component analysis performed by using molecular
      dynamics trajectories suggests that binding of ADP and ATP to extracellular
      signal-regulated kinase 2 change motion directions of two helices alpha1 and
      alpha2. Residue-based free energy decomposition method was adopted to calculate
      contributions of separate residues to associations of ADP and ATP with
      extracellular signal-regulated kinase 2. The results show that ADP and ATP
      produce strong CH-pi interactions with five residues Ile29, Val37, Ala50, Leu105,
      and Leu154. In addition, five hydrogen bonding interactions of ADP and ATP with
      residues Lys52, Gln103, Asp104, and Met106 also stabilize bindings of ADP and ATP
      to extracellular signal-regulated kinase 2. Overall, the CH-pi interactions of
      ATP with five residues Ile29, Val37, Ala50, Leu105, and Leu154 are stronger than
      ADP. This study is expected to contribute a significant theoretical hint for
      designs of anticancer drugs targeting extracellular signal-regulated kinase 2.

PMID- 27696675
TI  - MicroRNA let-7g possesses a therapeutic potential for peripheral artery disease.
AB  - Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis
      and conveys a significant health burden globally. Critical limb ischaemia
      encompasses the most severe consequence of PAD. Our previous studies indicate
      that microRNA let-7g prevents atherosclerosis and improves endothelial functions.
      This study aimed to investigate whether and how let-7g therapy may improve blood
      flow to ischaemic limbs. The present study shows that let-7g has multiple pro
      angiogenic effects on mouse ischaemic limb model and could be a potential
      therapeutic agent for PAD. Mice receiving intramuscular injection of let-7g had
      more neovascularization, better local perfusion and increased recruitment of
      endothelial progenitor cells after hindlimb ischaemia. The therapeutic effects of
      let-7g's on angiogenesis are mediated by multiple regulatory machinery. First,
      let-7g increased expression of vascular endothelial growth factor-A (VEGF-A) and
      VEGF receptor-2 (VEGFR-2) through targeting their upstream regulators HIF-3alpha
      and TP53. In addition, let-7g affected the splicing factor SC35 which
      subsequently enhanced the alternative splicing of VEGF-A from the anti-angiogenic
      isoform VEGF-A165b towards the pro-angiogenic isoform VEGF-A164a . The
      pleiotropic effects of let-7g on angiogenesis imply that let-7g may possess a
      therapeutic potential in ischaemic diseases.

PMID- 27696677
TI  - Human platelet antigens in Burmese, Karen and north-eastern Thais.
AB  - OBJECTIVES: A comparative study of allele frequencies at HPA-1 to -6 and HPA-15
      in Burmese and Karen populations as well as at HPA-15 in north-eastern Thais
      (NET) is presented. BACKGROUND: Human platelet antigens (HPAs) are clinically
      important in several immune platelet disorders, including foetal and neonatal
      alloimmune thrombocytopenia (FNAIT), post-transfusion purpura (PTP) and platelet
      transfusion refractoriness (PTR). The knowledge of antigen frequencies in a
      population is essential for the evaluation of patients suffering from immune
      mediated platelet disorders. METHODS: A total of 285 unrelated, healthy Burmese,
      242 Karen and 300 NET were recruited to this study. Genotype and allele
      frequencies of HPA-1 to -6 and HPA-15 were defined using polymerase chain
      reaction sequence-specific primers (PCR-SSP) RESULTS: No individuals homozygous
      for HPA-1bb, -2bb, -4bb, -5bb and -6bb were detected. HPA-1a, -2a, -4a, -5a and 
      6a were present in all samples of Burmese and Karen origin. HPA-1b, -2b, -4b, -5b
      and -6b were rare in these populations. The frequencies of HPA-3a/-3b were
      60.4/39.6% in Burmese and 55.8/44.2% in Karen, respectively. Frequencies of HPA
      15a/-15b were 57.2/42.8% in Burmese, 52.5/47.5% in Karen and 49.8/50.2% in NET.
      CONCLUSIONS: The frequencies of HPA genotypes in our study indicates that HPA-1a,
      -2a, -4a, -5a and -6a are unlikely involved in FNAIT, PTP and PTR in Burmese and
      Karen populations. However, HPA-1b, -2b, -3a, -3b, -4b, -5b, -6b, -15a and -15b
      may likely stimulate alloantibodies in these populations.

PMID- 27696676
TI  - Severity of experimental traumatic brain injury modulates changes in
      concentrations of cerebral free amino acids.
AB  - In this study, concentrations of free amino acids (FAA) and amino group
      containing compounds (AGCC) following graded diffuse traumatic brain injury (mild
      TBI, mTBI; severe TBI, sTBI) were evaluated. After 6, 12, 24, 48 and 120 hr
      aspartate (Asp), glutamate (Glu), asparagine (Asn), serine (Ser), glutamine
      (Gln), histidine (His), glycine (Gly), threonine (Thr), citrulline (Cit),
      arginine (Arg), alanine (Ala), taurine (Tau), gamma-aminobutyrate (GABA),
      tyrosine (Tyr), S-adenosylhomocysteine (SAH), l-cystathionine (l-Cystat), valine
      (Val), methionine (Met), tryptophane (Trp), phenylalanine (Phe), isoleucine
      (Ile), leucine (Leu), ornithine (Orn), lysine (Lys), plus N-acetylaspartate (NAA)
      were determined in whole brain extracts (n = 6 rats at each time for both TBI
      levels). Sham-operated animals (n = 6) were used as controls. Results
      demonstrated that mTBI caused modest, transient changes in NAA, Asp, GABA, Gly,
      Arg. Following sTBI, animals showed profound, long-lasting modifications of Glu,
      Gln, NAA, Asp, GABA, Ser, Gly, Ala, Arg, Citr, Tau, Met, SAH, l-Cystat, Tyr and
      Phe. Increase in Glu and Gln, depletion of NAA and Asp increase, suggested a link
      between NAA hydrolysis and excitotoxicity after sTBI. Additionally, sTBI rats
      showed net imbalances of the Glu-Gln/GABA cycle between neurons and astrocytes,
      and of the methyl-cycle (demonstrated by decrease in Met, and increase in SAH and
      l-Cystat), throughout the post-injury period. Besides evidencing new potential
      targets for novel pharmacological treatments, these results suggest that the
      force acting on the brain tissue at the time of the impact is the main
      determinant of the reactions ignited and involving amino acid metabolism.

PMID- 27696678
TI  - Effects of a progressive muscle relaxation intervention on dementia symptoms,
      activities of daily living, and immune function in group home residents with
      dementia in Japan.
AB  - AIM: To evaluate the effects of progressive muscle relaxation on the behavioral
      and psychological symptoms of dementia, activities of daily living, and immune
      function of elderly patients with dementia in group homes. METHODS: The
      participants were ranked by their group home unit. Odd ranks were assigned to the
      intervention group and even ranks to the control group. The intervention group
      participated in progressive muscle relaxation for 15 min each day for 90 days in
      the group environment; the control group members continued with their normal
      routine. All the participants' secretory immunoglobulin A was measured and they
      were assessed with the Neuropsychiatric Inventory-Nursing Home version, Nishimura
      Mental State Scale for the Elderly, and Nishimura Activities of Daily Living
      Scale. RESULTS: The intervention group comprised 18 participants from six units
      and the control group comprised 19 participants from five units. After the
      intervention, the Neuropsychiatric Inventory scores were significantly better in
      the intervention group, particularly for Agitation and Anxiety. The intervention
      group also showed significantly lower Apathy and Irritability scores and
      significant improvement in the Interest, Volition, and Social relationships
      scores on the Mental State Scale, with improvement in the activities of daily
      living total. However, there was no difference in the secretory immunoglobulin A
      level between the groups. CONCLUSION: The results suggest that progressive muscle
      relaxation improves the behavioral and psychological symptoms of dementia and
      activities of daily living in group home residents with dementia, but does not
      affect their immune function.

PMID- 27696679
TI  - Pigmented squamous cell carcinoma in an adolescent following long-term treatment
      with voriconazole.

PMID- 27696681
TI  - Dynamics of Epstein-Barr viral load after hematopoietic stem cell transplantation
      and effect of preemptive rituximab therapy.
AB  - BACKGROUND: Epstein-Barr virus (EBV) displays oncogenic properties, particularly
      in the immunocompromised host. Notably, hematopoietic stem cell transplantation
      (HSCT) recipients with a detectable blood EBV viral load (BEBVL) are considered
      at higher risk of post-transplant lymphoproliferative diseases (PTLD). Therefore,
      BEBVL is monitored after HSCT, and preemptive rituximab may be used in patients
      with high values. However, little is known about post-HSCT BEBVL dynamics, and
      the threshold that should lead to anti-CD20 therapy is poorly defined. METHODS:
      We retrospectively analyzed the post-HSCT BEBVL of 332 adult HSCT recipients in
      our center from 2005 to 2013, including the effect of rituximab. RESULTS:
      Detection of BEBVL >100, 1000, 5000, 10 000, and 50 000 copies/mL occurred in,
      respectively, 77.7%, 69.6%, 37.0%, 27.1%, and 7.5% of the patients after a
      respective median time of 9, 14, 15, 16, and 14 weeks. No BEBVL threshold was
      associated with an overall survival difference. Seventy-eight patients received
      rituximab, with a BEBVL decrease in most. Among patients with detectable BEBVL,
      long-term survival did not differ in rituximab treated and non-treated, except
      for patients with BEBVL >=50 000. Only one case of PTLD was observed.
      CONCLUSIONS: BEBVL is frequently detectable after HSCT, but suggests no strong
      association with survival. Preemptive rituximab therapy threshold remains to be
      defined.

PMID- 27696682
TI  - Utility of Ecological Risk Factors for Evaluation of Transplant Center
      Performance.
AB  - There is substantial evidence across different healthcare contexts that social
      determinants of health are strongly associated with morbidity and mortality in
      the United States. These factors, including socioeconomic status, behavior and
      environmental risks, education, social support, healthy food, and access to
      healthcare also vary widely by region and individual communities. One of the
      implications of heterogeneity in these risks is the potential impact on measured
      quality of healthcare providers. In particular, there is concern that providers
      treating disproportionally vulnerable communities may be disadvantaged by lack of
      risk adjustment for these factors that affect health but not indicators of
      quality of care. Recently, the National Quality Forum has endorsed risk
      adjustment for sociodemographic characteristics based on these concerns. These
      issues are salient to transplant programs since social determinants of health
      impact transplant patient outcomes and vary by region. In this viewpoint, we
      argue that integration of ecological (area-level) factors in risk adjustment
      models used to assess transplant center quality should be strongly considered. We
      believe this reform could be accomplished rapidly, would attenuate disparities in
      access to care by reducing disincentives to treat patients from vulnerable
      communities, and improve risk adjustment and calibration of models used for
      center evaluations.

PMID- 27696680
TI  - Autoregulation of retinal homeobox (rax) gene promoter activity through a highly
      conserved genomic element.
AB  - The Retinal homeobox (rax) gene is expressed in vertebrate retinal progenitor and
      stem cells and is essential for retinal development. In frogs, rax is expressed
      in the ciliary marginal zone (CMZ), a region containing retinal progenitor and
      stem cells at the anterior of the eye. Little is known regarding regulation of
      rax transcription and regulation of transcription of rax targets. We found that
      three ultra-conserved genomic elements (UCEs) flanking the rax coding region
      regulate expression of a rax promoter-GFP transgene in Xenopus tadpoles. One of
      these elements, UCE1, regulates expression of the transgene in the dorsal CMZ.
      UCE1 contains a Rax binding site, PCE-1. We demonstrate that rax regulates
      expression of the transgene through the PCE-1 site found in UCE1. Therefore, rax
      transcription in the CMZ is controlled, in part, by autoregulatory mechanisms.

PMID- 27696683
TI  - The APSES transcription factor Vst1 is a key regulator of development in
      microsclerotium- and resting mycelium-producing Verticillium species.
AB  - Plant pathogens of the genus Verticillium pose a threat to many important crops
      worldwide. They are soil-borne fungi which invade the plant systemically, causing
      wilt symptoms. We functionally characterized the APSES family transcription
      factor Vst1 in two Verticillium species, V. dahliae and V. nonalfalfae, which
      produce microsclerotia and melanized hyphae as resistant structures,
      respectively. We found that, in V. dahliae Deltavst1 strains, microsclerotium
      biogenesis stalled after an initial swelling of hyphal cells and cultures were
      never pigmented. In V. nonalfalfae Deltavst1, melanized hyphae were also absent.
      These results suggest that Vst1 controls melanin biosynthesis independent of its
      role in morphogenesis. The absence of vst1 also had a great impact on sporulation
      in both species, affecting the generation of the characteristic verticillate
      conidiophore structure and sporulation rates in liquid medium. In contrast with
      these key roles in development, Vst1 activity was dispensable for virulence. We
      performed a microarray analysis comparing global transcription patterns of wild
      type and Deltavst1 in V. dahliae. G-protein/cyclic adenosine monophosphate (G
      protein/cAMP) signalling and mitogen-activated protein kinase (MAPK) cascades are
      known to regulate fungal morphogenesis and virulence. The microarray analysis
      revealed a negative interaction of Vst1 with G-protein/cAMP signalling and a
      positive interaction with MAPK signalling. This analysis also identified Rho
      signalling as a potential regulator of morphogenesis in V. dahliae, positively
      interacting with Vst1. Furthermore, it exposed the association of secondary
      metabolism and development in this species, identifying Vst1 as a potential co
      regulator of both processes. Characterization of the putative Vst1 targets
      identified in this study will aid in the dissection of specific aspects of
      development.

PMID- 27696684
TI  - A literature review of reports of the stability and storage of common injectable
      chemotherapy agents used in veterinary patients.
AB  - Many chemotherapy drugs used in human patients are discarded after single use or
      within 24 h of reconstitution, as per the manufacturer's product label
      recommendations. This can be wasteful and costly to veterinary clients. This
      report reviews the published stability and storage data for 19 injectable
      chemotherapy drugs commonly used in veterinary medicine. Based on these data,
      storage procedures are presented, assuming aseptic technique and a closed system
      drug transfer device (CSDTD) are used for drug preparation and handling. Further
      studies on the risk of microbiological contamination of chemotherapeutics using a
      CSDTD, and validated high quality drug assays such as stability-indicating high
      performance liquid chromatography, are required. The authors' intent is not to
      supersede product label recommendations, but to suggest that longer storage
      without significant loss of drug efficacy may be possible, thus reducing the
      costs of chemotherapeutics to some veterinary clients.

PMID- 27696685
TI  - Structural basis for endotoxin neutralization by the eosinophil cationic protein.
AB  - Acute infection by Gram-negative pathogens can induce an exacerbated immune
      response that leads to lethal septic shock syndrome. Bacterial lipopolysaccharide
      (LPS) is a major pathogen-associated molecular pattern molecule that can initiate
      massive and lethal immune system stimulation. Therefore, the development of new
      and effective LPS-neutralizing agents is a top priority. The eosinophil cationic
      protein (ECP) is an antimicrobial protein secreted in response to infection, with
      a remarkable affinity for LPS. In the present study, we demonstrate that ECP is
      able to neutralize bacterial LPS and inhibit tumor necrosis factor-alpha
      production in human macrophages. We also characterized ECP neutralizing activity
      using progressively truncated LPS mutants, and conclude that the polysaccharide
      moiety and lipid A portions are required for LPS-mediated neutralization. In
      addition, we mapped the structural determinants required for the ECP-LPS
      interaction by nuclear magnetic resonance. Our results show that ECP is able to
      neutralize LPS and therefore opens a new route for developing novel therapeutic
      agents based on the ECP structural scaffolding.

PMID- 27696686
TI  - Dehomocysteinylation is catalysed by the sirtuin-2-like bacterial lysine
      deacetylase CobB.
AB  - Hyperhomocysteinemia, which is characterized by elevated blood levels of the non
      protein amino acid homocysteine (Hcy), is an independent risk factor for many
      diseases, including cardiovascular diseases, neurodegenerative diseases and birth
      defects. The incorporation of homocysteine into proteins, known as protein N
      homocysteinylation, has been considered a major mechanism that contributes to
      hyperhomocysteinemia. However, the process of dehomocysteinylation, the N
      homocysteinylation substrates and the regulatory enzyme(s) remain largely
      unknown. In this study, we observed that the dehomocysteinylation reaction is a
      spontaneous process that can be inhibited by blocking -SH groups, which have been
      demonstrated to be critical for non-enzymatic dehomocysteinylation reactions. We
      also report that CobB, a known Sir2-like bacterial lysine deacetylase, catalyzes
      lysine dehomocysteinylation reactions both in vitro and in vivo. Our work
      provides insight into how this non-enzymatic modification might be removed from
      affected proteins, supplies potential targets for developing identification
      methods for N-homocysteine proteins, and identifies CobB as the first prokaryotic
      dehomocysteinylation enzyme.

PMID- 27696687
TI  - Phosphatidic acid induces decidualization by stimulating Akt-PP2A binding in
      human endometrial stromal cells.
AB  - Decidualization of human endometrial stromal cells (hESCs) is crucial for
      successful uterine implantation and maintaining pregnancy. We previously reported
      that phospholipase D1 (PLD1) is required for cAMP-induced decidualization of
      hESCs. However, the mechanism by which phosphatidic acid (PA), the product of
      PLD1 action, might regulate decidualization is not known. We confirmed that PA
      induced decidualization of hESCs by observing morphological changes and measuring
      increased levels of decidualization markers such as IGFBP1 and prolactin
      transcripts (P < 0.05). Treatment with PA reduced phosphorylation of Akt and
      consequently that of FoxO1, which led to the increased IGFBP1 and prolactin mRNA
      levels (P < 0.05). Conversely, PLD1 knockdown rescued Akt phosphorylation.
      Binding of PP2A and Akt increased in response to cAMP or PA, suggesting that
      their binding is directly responsible for the inactivation of Akt during
      decidualization. Consistent with this observation, treatment with okadaic acid, a
      PP2A inhibitor, also inhibited cAMP-induced decidualization by blocking Akt
      dephosphorylation.

PMID- 27696689
TI  - Public Healthcare Entitlements and Healthcare Utilisation among the Older
      Population in Ireland.
AB  - The use of direct out-of-pocket payments to finance general practitioner (GP)
      care by the majority of the population in Ireland is unusual in a European
      context. Currently, approximately 40% of the population have means-tested access
      to free GP care, while the remainder must pay the full out-of-pocket cost. In
      this paper, we use data from The Irish Longitudinal Study on Ageing (TILDA) to
      examine the impact of the current system of public healthcare entitlements on GP
      utilisation among the older population. Using difference-in-difference propensity
      score matching methods, we find significant effects of changes in public
      healthcare entitlements on GP utilisation (i.e. introducing user fees reduces
      utilisation, while removing them increases utilisation). There is limited
      evidence of offset effects on other types of healthcare utilisation. The results
      have direct implications for current Irish health policy, and add to the
      international literature on the effects of insurance on healthcare utilisation.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696688
TI  - Reduced visual disengagement but intact phasic alerting in young children with
      autism.
AB  - Children with autism may have difficulties with visual disengagement-that is,
      inhibiting current fixations and orienting to new stimuli in the periphery. These
      difficulties may limit these children's ability to flexibly monitor the
      environment, regulate their internal states, and interact with others. In typical
      development, visual disengagement is influenced by a phasic alerting network that
      increases the processing speed of the visual system after salient events. The
      role of the phasic alerting effect in the putative atypical disengagement
      performance in autism spectrum disorder (ASD) is not known. Here, we compared
      visual disengagement in six-year-old children with autism (N = 18) and typically
      developing children (N = 17) matched for age and nonverbal IQ. We manipulated
      phasic alerting during a visual disengagement task by adding spatially
      nonpredictive sounds shortly before the onset of the visual peripheral targets.
      Children with ASD showed evidence of delayed disengagement compared to the
      control group. Sounds facilitated visual disengagement similarly in both groups,
      suggesting typical modulation by phasic alerting in ASD in the context of this
      task. These results support the view that atypical visual disengagement in ASD is
      related to other factors than atypicalities in the alerting network. Autism Res
      2017, 10: 539-545. (c) 2016 The Authors Autism Research published by Wiley
      Periodicals, Inc. on behalf of International Society for Autism Research.

PMID- 27696690
TI  - New York University School of Medicine Drug Development Educational Program: 2
      Year Benchmark.
AB  - Drug development (DD) is a multidisciplinary process that spans the translational
      continuum, yet remains an understudied entity in medical schools and biomedical
      science institutes. In response to a growing interest and unmet need, we
      implemented a DD course series that details identification of viable molecular
      targets, clinical trial design, intellectual property, and marketing. Enrollment
      is open to faculty, postdoctoral trainees, and MD, PhD, and MS students. After 2
      years, 37 students and 23 students completed the fall and spring courses,
      respectively. Pre/post-surveys demonstrated gained knowledge across course
      topics, with mean survey scores increased by 66% (p < 0.001) after each course.
      Lectures for each course were consistently rated highly, with a mean course
      rating of 4.1/5. Through this program, trainees will have a more innovative
      approach toward identification of therapeutic targets and modalities.
      Furthermore, they will learn to integrate technology and biomedical informatics
      to find creative solutions in the DD process.

PMID- 27696691
TI  - iManage: A novel self-management app for sickle cell disease.

PMID- 27696692
TI  - Gene-Gene Interactions Among PRKCA, NOS3 and BDKRB2 Polymorphisms Affect the
      Antihypertensive Effects of Enalapril.
AB  - Protein kinase C (PKC) signalling is critically involved in the control of blood
      pressure. Angiotensin-converting enzyme inhibitors (ACEi) affect PKC expression
      and activity, which are partially associated with the responses to ACEi. We
      examined whether PRKCA (protein kinase C, alpha) polymorphisms (rs887797 C>T,
      rs1010544 T>C and rs16960228 G>A), or haplotypes, and gene-gene interactions
      within the ACEi pathway affect the antihypertensive responses in 104 hypertensive
      patients treated with enalapril as monotherapy. Patients were classified as poor
      responders (PR) or good responders (GR) to enalapril if their changes in mean
      arterial pressure were lower or higher than the median value, respectively. Multi
      factor dimensionality reduction was used to characterize interactions among
      PRKCA, NOS3 (nitric oxide synthase 3) and BDKRB2 (bradykinin receptor B2)
      polymorphisms. The TC+CC genotypes for the rs1010544 polymorphism were more
      frequent in GR than in PR (p = 0.037). Conversely, the GA+AA genotypes for the
      rs16960228 polymorphism, and the CTA haplotype, were more frequent in PR than in
      GR (p = 0.040 and p = 0.008, respectively). Moreover, the GG genotype for the
      PRKCA rs16960228 polymorphism was associated with PR or GR depending on the
      genotypes for the rs2070744 (NOS3) and rs1799722 (BDKRB2) polymorphisms (p =
      0.012). Our results suggest that PRKCA polymorphisms and gene-gene interactions
      within the ACEi pathway affect the antihypertensive responses to enalapril.

PMID- 27696693
TI  - The silent overall burden of foot disease in a representative hospitalised
      population.
AB  - The aims of this study were to investigate the point prevalence, and associated
      independent factors, for foot disease (ulcers, infections and ischaemia) in a
      representative hospitalised population. We included 733 (83%) of 883 eligible
      adult inpatients across five representative Australian hospitals on one day. We
      collected an extensive range of self-reported characteristics from participants.
      We examined all participants to clinically diagnose foot disease (ulcers,
      infections and ischaemia) and amputation procedures. Overall, 72 participants
      (9.8%) [95% confidence interval (CI):7.2-11.3%] had foot disease. Foot ulcers, in
      49 participants (6.7%), were independently associated with peripheral neuropathy,
      peripheral arterial disease, previous foot ulcers, trauma and past surgeon
      treatment (P < 0.05). Foot infections, in 24 (3.3%), were independently
      associated with previous foot ulcers, trauma and past surgeon treatment (P <
      0.01). Ischaemia, in 33 (4.5%), was independently associated with older age,
      smokers and past surgeon treatment (P < 0.01). Amputation procedures, in 14
      (1.9%), were independently associated with foot infections (P < 0.01). We found
      that one in every ten inpatients had foot disease, and less than half of those
      had diabetes. After adjusting for diabetes, factors linked with foot disease were
      similar to those identified in diabetes-related literature. The overall inpatient
      foot disease burden is similar in size to well-known medical conditions and
      should receive similar attention.

PMID- 27696694
TI  - The care of transmetatarsal amputation in diabetic foot gangrene.
AB  - Diabetic foot ulcerations may determine minor or major amputation, with a high
      impact on patients' life expectation and quality of life and on economic burden.
      Among minor amputations, transmetatarsal amputation (TMA) appears to be the most
      effective in terms of limb salvage rates and in maintaining foot and ankle
      biomechanics. In spite of this, TMA needs particular pre- and postoperative
      management in order to avoid the frequent failure rates. A systematic review was
      undertaken of studies concerning TMA and its care in diabetic foot gangrene.
      Studies were identified by searching the MEDLINE, Scopus and Science Direct
      databases until 13 January 2016. All studies were assessed using the Downs and
      Black quality checklist. Of the 348 records found, 86 matched our inclusion
      criteria. After reading the full-text articles, we decided to exclude 35
      manuscripts because of the following reasons: (1) no innovative or important
      content, (2) no multivariable analysis, (3) insufficient data, (4) no clear
      potential biases or strategies to solve them, (5) no clear endpoints and (6)
      inconsistent or arbitrary conclusions. The final set included 51 articles. In the
      current literature, there are less data about TMA, indication for the selection
      of patients, outcomes and complications. Generally, the judgment of an
      experienced physician is one of the best indicators of subsequent healing. Ankle
      brachial indices, toe pressures, laser Doppler skin perfusion pressures,
      angiography and Doppler assessment of foot vasculature may help physicians in
      this decision. In any case, despite the presumed lower healing rate, it is
      reasonable to pursue a TMA in a patient with a higher likelihood of continued
      ambulation. Furthermore, tailored wound closure, adjuvant local treatments and
      the choice of the most appropriate antibiotic therapy, when infection occurs, are
      pivotal elements for the success of TMA procedures. TMA is a valuable option for
      diabetic foot gangrene that can prevent major limb loss and minimise loss of
      function, thus improving the quality of life for diabetic patients.

PMID- 27696695
TI  - Blunt chest trauma in a non-specialist centre: Right treatment, right place?
AB  - OBJECTIVES: To compare patient characteristics, management and outcomes for
      patients admitted with isolated blunt chest trauma, managed by medical or
      surgical teams. METHODS: We reviewed adult patients admitted with blunt chest
      trauma between 1 September 2006 and 31 August 2011 to a secondary hospital in New
      Zealand. Inclusion criteria were: blunt chest trauma, with at least one
      radiologically demonstrated rib fracture. The primary outcome was in-hospital
      mortality, and secondary outcomes were development of pneumonia, and use of
      analgesia. RESULTS: Seventy-two patients were included. Thirty-three patients
      were managed by medical teams and 39 by surgical teams. In-hospital mortality was
      greater amongst medical patients 5/33 (15%) versus surgical 0/39 (0%); P = 0.012.
      Pneumonia occurred in 15/33 (45%); medical patients versus surgical 2/39 (5%), P
      <0.001. Use of epidural, regional or patient-controlled analgesia was greater in
      the group managed by surgical teams (12/39 [30.7%] vs 1/33 [3%] P = 0.002).
      Medically managed patients were older (median 73 vs 63 years; P = 0.02), had a
      higher Charlson Comorbidity Index (median 5 vs 3; P = 0.013). The mechanism of
      injury for medically managed patients was more likely to be low trauma fall
      compared to surgically managed patients (28/33 [85%] vs 9/39 [27%]; P <0.0001).
      CONCLUSION: Amongst patients with isolated blunt chest trauma, those managed by
      medical teams were older, had more comorbidities and were more likely to have
      become injured with a low trauma fall than those managed by surgical teams. They
      had less access to analgesic options, developed pneumonia more often and had
      higher mortality.

PMID- 27696697
TI  - Prescribing antibiotics in diabetic foot infection: what is the role of initial
      microscopy and culture of tissue samples?
AB  - The aim of this study was to evaluate the role of microscopy, Gram stain and the
      culture of tissue samples in the antibiotic treatment of patients with diabetic
      foot infection. A retrospective review of patients with a diabetic foot infection
      was undertaken. Data analysed included the severity of infection, antibiotic
      prescribing patterns, microscopy and culture results. A total of 71 patients were
      included, from whom 114 tissue samples were collected. Gram stain results were in
      agreement with final culture results in 45.8% (n = 54) of samples. Overall
      sensitivity and specificity of the Gram stains were low (74.5% and 69.8%,
      respectively), although the specificity for Gram-negative rods was high (98.5%).
      The presence or absence of 'pus cells' on microscopy was a poor predictor of
      culture results. Empirical prescribing of antibiotics was in accordance with
      local policy in 31.1% of patients, improving to 86.8 % following culture results.
      Microscopy, a skilled laboratory procedure, was generally a poor predictor of
      tissue culture results. However, the presence of Gram-negative rods was
      suggestive of isolation in the culture of such organisms and could allow the
      early broadening of antibiotic treatment. Despite initial poor compliance of
      empirical antibiotic treatment regimens, prescribing was adjusted in light of
      culture results, suggesting these were important for clinicians.

PMID- 27696696
TI  - Growth of Pseudomonas taiwanensis VLB120?C biofilms in the presence of n-butanol.
AB  - Biocatalytic processes often encounter problems due to toxic reactants and
      products, which reduce biocatalyst viability. Thus, robust organisms capable of
      tolerating or adapting towards such compounds are of high importance. This study
      systematically investigated the physiological response of Pseudomonas taiwanensis
      VLB120?C biofilms when exposed to n-butanol, one of the potential next generation
      biofuels as well as a toxic substance using microscopic and biochemical methods.
      Initially P. taiwanensis VLB120?C biofilms did not show any observable growth in
      the presence of 3% butanol. Prolonged cultivation of 10 days led to biofilm
      adaptation, glucose and oxygen uptake doubled and consequently it was possible to
      quantify biomass. Complementing the medium with yeast extract and presumably
      reducing the metabolic burden caused by butanol exposure further increased the
      biomass yield. In course of cultivation cells reduced their size in the presence
      of n-butanol which results in an enlarged surface-to-volume ratio and thus
      increased nutrient uptake. Finally, biofilm enhanced its extracellular polymeric
      substances (EPS) production when exposed to n-butanol. The predominant response
      of these biofilms under n-butanol stress are higher energy demand, increased
      biomass yield upon medium complements, larger surface-to-volume ratio and
      enhanced EPS production. Although we observed a distinct increase in biomass in
      the presence of 3% butanol it was not possible to cultivate P. taiwanensis
      VLB120?C biofilms at higher n-butanol concentrations. Thereby this study shows
      that biofilms are not per se tolerant against solvents, and need to adapt to
      toxic n-butanol concentrations.

PMID- 27696698
TI  - The relationship between cognitive and neuroimaging outcomes in children treated
      for acute lymphoblastic leukemia with chemotherapy only: A systematic review.
AB  - Cognitive late-effects have been identified in patients treated with chemotherapy
      only protocols for childhood acute lymphoblastic leukemia (ALL), yet the
      underlying neuropathology is not well understood. This review synthesized recent
      findings from eight articles investigating the relationship between
      neurocognitive and neuroimaging outcomes for patients treated for ALL with
      chemotherapy-only protocols. Reported cognitive domains, imaging methods, and
      neuroanatomy examined were variable. Despite this, 62.5% (n = 5) of the reviewed
      studies found a significant relationship between cognitive and imaging outcomes.
      Greater understanding of the effects of treatment on neuroanatomy and cognitive
      outcomes is critical for proactively managing ALL cognitive late-effects.
      Research directions are suggested.

PMID- 27696699
TI  - Enhancement of wound closure by modifying dual release patterns of stromal
      derived cell factor-1 and a macrophage recruitment agent from gelatin hydrogels.
AB  - The objective of the present study is to evaluate the effects of the release
      patterns of stromal derived factor (SDF)-1 and sphingosine-1 phosphate agonist
      (SEW2871), used as MSC and macrophage recruitment agents, on the wound closure of
      diabetic mouse skin defects. To achieve different release patterns, hydrogels
      were prepared using two types of gelatin with isoelectric points (IEP) of 5 and
      9, into which SDF-1 and SEW2871 were then incorporated in various combinations.
      When the hydrogels incorporating SDF-1 and SEW2871 were applied into wound
      defects of diabetic mice, the number of MSCs and macrophages recruited to the
      defects and the levels of pro- and anti- inflammatory cytokines were found to be
      dependent on the release profiles of SDF-1 and SEW2871. Of particular interest
      was the case of a rapid release of SDF-1 combined with a controlled release of
      SEW2871. This resulted in a higher number of M2 macrophages and gene expression
      levels of anti-inflammatory cytokines 3 days after implantation and faster wound
      closure than when pairing the controlled release of SDF-1 with a rapid release of
      SEW2871. Therefore, the present study demonstrates that different release
      patterns of SDF-1 and SEW2871 can enhance the in vivo recruitment of MSCs and
      macrophages, and can promote skin wound closure through the modulation of
      inflammation. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696700
TI  - Predictors of Longitudinal Quality of Life in Juvenile Localized Scleroderma.
AB  - OBJECTIVE: Localized scleroderma can negatively affect children's quality of life
      (QoL), but predictors of impact have not been well described. We sought to
      identify predictors of QoL impact in juvenile localized scleroderma patients.
      METHODS: We analyzed longitudinal data from a single-center cohort of juvenile
      localized scleroderma patients, using hierarchical generalized linear modeling
      (HGLM) to identify predictors of QoL impact. HGLM is useful for nested data and
      allows for evaluation of both time-variant and time-invariant predictors.
      RESULTS: The number of extracutaneous manifestations (ECMs; e.g., joint
      contracture and hemifacial atrophy) and female sex predicted negative QoL impact,
      defined as a Children's Dermatology Life Quality Index score >1 (P = 0.019 for
      ECMs and P = 0.002 for female sex). As the time since the initial visit
      increased, the odds of reporting a negative QoL impact decreased (P < 0.001).
      CONCLUSION: Our results suggest that ECMs, sex, and time since initial visit are
      more predictive of QoL impact in localized scleroderma than cutaneous features.
      Further study is required to determine which ECMs have the most impact on QoL,
      which factors underlie sex differences in QoL in localized scleroderma, and why
      increasing the time since the initial visit appears to be protective. An improved
      understanding of predictors of QoL impact may allow for the identification of
      patients at risk of poorer outcomes and for the tailoring of treatment and
      psychosocial support.

PMID- 27696701
TI  - The long-term recurrence risk of patients with unprovoked venous thromboembolism:
      an observational cohort study.
AB  - : Essentials Long-term recurrence risk of venous thromboembolism (VTE) is
      uncertain. We performed a prospective cohort study of 839 patients with first
      unprovoked VTE. VTE recurrence risk is high, particularly in men with proximal
      thrombosis or pulmonary embolism. Sex and VTE site determine the recurrence risk
      and should be considered for patient counseling. SUMMARY: Background The long
      term recurrence risk (ltRR) of venous thromboembolism (VTE) is uncertain.
      Objective To assess the ltRR of patients with first unprovoked VTE.
      Patients/methods Patients were classified into three categories: distal deep vein
      thrombosis (DVT), proximal DVT or pulmonary embolism (PE), that is, PE associated
      with DVT or isolated PE. Patients with major thrombophilia or antithrombotic
      therapy were excluded. The endpoint was recurrent symptomatic VTE. Results A
      total of 839 patients were followed for a median of 7.7 years. VTE recurred in
      263 patients (31%). After 10 and 20 years, the cumulative ltRR was 32% (95%
      confidence interval [CI], 29-36) and 44% (95% CI, 38-49) with 3.9 (95% CI, 3.3
      4.6) and 3.3 (95% CI, 2.7-4.0) events per 100 patient-years, respectively. The
      adjusted hazard ratio was 2.1 (95% CI, 1.4-3.2) and 2.1 (95% CI, 1.4-3.2) for
      patients with proximal DVT or PE compared with patients with distal DVT and was
      2.1 (95% CI, 1.6-2.9) for men compared with women. At 10 years, 4.7 (95% CI, 3.8
      5.8) events per 100 patient-years occurred in men with proximal DVT or PE, 2.4
      (95% CI, 1.2-4.4) in men with distal DVT, 1.9 (95% CI, 1.2-2.8) in women with
      proximal DVT or PE and 0.9 (95% CI, 0.2-1.9) in women with distal DVT. Conclusion
      The ltRR of patients with first unprovoked VTE is high and dependent upon sex and
      VTE site.

PMID- 27696704
TI  - Erratum.

PMID- 27696702
TI  - Distinct roles of immunoreceptor tyrosine-based motifs in immunosuppressive
      indoleamine 2,3-dioxygenase 1.
AB  - The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) catalyses the initial, rate
      limiting step in tryptophan (Trp) degradation, resulting in tryptophan starvation
      and the production of immunoregulatory kynurenines. IDO1's catalytic function has
      long been considered as the one mechanism responsible for IDO1-dependent immune
      suppression by dendritic cells (DCs), which are master regulators of the balance
      between immunity and tolerance. However, IDO1 also harbours immunoreceptor
      tyrosine-based inhibitory motifs, (ITIM1 and ITIM2), that, once phosphorylated,
      bind protein tyrosine phosphatases, (SHP-1 and SHP-2), and thus trigger an
      immunoregulatory signalling in DCs. This mechanism leads to sustained IDO1
      expression, in a feedforward loop, which is particularly important in restraining
      autoimmunity and chronic inflammation. Yet, under specific conditions requiring
      that early and protective inflammation be unrelieved, tyrosine-phosphorylated
      ITIMs will instead bind the suppressor of cytokine signalling 3 (SOCS3), which
      drives IDO1 proteasomal degradation and shortens the enzyme half-life. To dissect
      any differential roles of the two IDO1's ITIMs, we generated protein mutants by
      replacing one or both ITIM-associated tyrosines with phospho-mimicking glutamic
      acid residues. Although all mutants lost their enzymic activity, the ITIM1 - but
      not ITIM2 mutant - did bind SHPs and conferred immunosuppressive effects on DCs,
      making cells capable of restraining an antigen-specific response in vivo.
      Conversely, the ITIM2 mutant would preferentially bind SOCS3, and IDO1's
      degradation was accelerated. Thus, it is the selective phosphorylation of either
      ITIM that controls the duration of IDO1 expression and function, in that it
      dictates whether enhanced tolerogenic signalling or shutdown of IDO1-dependent
      events will occur in a local microenvironment.

PMID- 27696703
TI  - Personalized Physical Therapy Versus Usual Care for Patients With Systemic
      Sclerosis: A Randomized Controlled Trial.
AB  - OBJECTIVE: To compare a physical therapy program to usual care of systemic
      sclerosis (SSc) patients on disability. METHODS: A 12-month followup, parallel
      group randomized controlled trial involving a modified Zelen design was conducted
      in 4 tertiary-care hospitals. Patients were enrolled if they had a disability
      rating >=0.5 on the Health Assessment Questionnaire disability index (HAQ DI) or
      symptoms of decreased mouth opening or limited range of motion of at least 1
      joint. The experimental intervention (n = 112, of which 110 were analyzed) was a
      1-month personalized supervised physical therapy program provided by trained care
      providers followed by home sessions. The comparator (n = 108, and all 108 were
      analyzed) was usual care that could include ambulatory physical therapy. The
      primary outcome was the HAQ DI score. RESULTS: There was no statistically
      significant difference in disability at 12 months (HAQ DI score between-group
      difference -0.01 [95% confidence interval (95% CI) -0.15, 0.13]; P = 0.86).
      Disability was reduced at 1 month for patients in the physical therapy group (HAQ
      DI between-group difference -0.14 [95% CI -0.24, -0.03]; P = 0.01); at 6 months
      the HAQ DI score between-group difference was -0.12 (95% CI -0.23, 0.01); P =
      0.054. There was a statistically significant difference for hand mobility and
      function, and for pain, at 1 month. Microstomia was lower in the physical therapy
      group at 1, 6, and 12 months (between-group difference at 12 months 1.62 [95% CI
      0.32, 2.93]; P = 0.01). No differences in adverse effects were observed.
      CONCLUSION: A personalized physical therapy program did not reduce disability at
      12 months but had short-term benefits for patients with SSc.

PMID- 27696705
TI  - What is the chance all your trainees will pass the next Fellowship exam: A
      statistician's view.
AB  - Your department has had a good track record over many years for preparing
      trainees to successfully sit for the ACEM Fellowship exam. On average the pass
      rate for your trainees is over 80%. Then, to your dismay, suddenly only two of
      five of your trainees pass the latest Fellowship exam. Does this anomaly
      necessitate an urgent review of your department's training programme, or is it
      just a statistical quirk? Let us suppose you can prepare candidates so that they
      all have at least an 80% chance of passing. The probability that all five
      candidates would have passed is 32.8% (or 0.85 ) based on the multiplication rule
      of probability for independent events. The probability that only two of five
      passed is 5.1% (or 10 * 0.82 * 0.23 ) based on the binomial distribution, which
      is a probability distribution analogous to the normal distribution. The
      construction of the binomial distribution depends on two parameters: (i) number
      of candidates sitting ('n'), and (ii) probability of passing for any individual
      candidate ('P'). The distribution gives the probability that 'x' number of
      individuals will pass when 'n' number of individuals sit. Thus despite an 80%
      pass rate historically, the probability that only two of five candidates will
      pass is not negligible at 5.1%. It is an anomaly, which we may choose not to act
      on unless it is recurrent, noting it will be expected to occur naturally about
      one time out of 20. The real challenge is to maintain or increase that individual
      probability at 80% or higher.

PMID- 27696707
TI  - Pathogenesis of the antiphospholipid syndrome revisited: time to challenge the
      dogma: reply.

PMID- 27696706
TI  - The cephalic labial gland secretions of two socially parasitic bumblebees Bombus
      hyperboreus (Alpinobombus) and Bombus inexspectatus (Thoracobombus) question
      their inquiline strategy.
AB  - Social parasitic Hymenopterans have evolved morphological, chemical, and
      behavioral adaptations to overcome the sophisticated recognition and defense
      systems of their social host to invade host nests and exploit their worker force.
      In bumblebees, social parasitism appeared in at least 3 subgenera independently:
      in the subgenus Psithyrus consisting entirely of parasitic species, in the
      subgenus Alpinobombus with Bombus hyperboreus, and in the subgenus Thoracobombus
      with B. inexspectatus. Cuckoo bumblebee males utilize species-specific cephalic
      labial gland secretions for mating purposes that can impact their inquiline
      strategy. We performed cephalic labial gland secretions in B. hyperboreus, B.
      inexspectatus and their hosts. Males of both parasitic species exhibited high
      species specific levels of cephalic gland secretions, including different main
      compounds. Our results showed no chemical mimicry in the cephalic gland
      secretions between inquilines and their host and we did not identify the
      repellent compounds already known in other cuckoo bumblebees.

PMID- 27696708
TI  - Pedicled medial sural perforator flap for the reconstruction of knee defects.
AB  - Soft tissue defects exposing the patellar tendon or bone are common in patients
      who have experienced trauma or implant infection. The purpose of this article is
      to present our experience of six patients who underwent reconstruction of soft
      tissue defects of the knee using a pedicled medial sural perforator flap. Between
      November 2013 and November 2015, six patients who presented with a soft tissue
      defect overlying the knee were admitted to our hospital. After adequate
      debridement or wide excision of the tumour, these patients underwent pedicled
      medial sural perforator flap placement to resurface the complex soft tissue
      defects and to provide a gliding surface for the exposed patellar tendon. The
      patients' age, comorbidity, aetiology, defect size and location, flap size,
      perforator numbers and lengths, outcome and follow-up period were reviewed. The
      six medial sural perforator flaps survived completely, and the wounds healed
      satisfactorily over a mean follow-up of 21.5 months (range, 6-51 months). Donor
      sites were closed primarily or covered with a split-thickness skin graft. The
      medial sural perforator flap is a reliable flap for coverage of defects overlying
      the knee. The thin and pliable flap, long pedicle length and less donor site
      mobility benefit patients. Thus, the medial sural perforator flap may be a
      valuable alternative for defect reconstructions overlying the knee, which
      produces satisfactory results both functionally and cosmetically.

PMID- 27696709
TI  - Axially vascularized tissue-engineered bone constructs retain their in vivo
      angiogenic and osteogenic capacity after high-dose irradiation.
AB  - In order to introduce bone tissue engineering to the field of oncological
      reconstruction, we are investigating for the first time the effect of various
      doses of ionizing irradiation on axially vascularized bone constructs. Synthetic
      bone constructs were created and implanted in 32 Lewis rats. Each construct was
      axially vascularized through an arteriovenous loop made by direct anastomosis of
      the saphenous vessels. After 2 weeks, the animals received ionizing irradiation
      of 9 Gy, 12 Gy and 15 Gy, and were accordingly classified to groups I, II and
      III, respectively. Group IV was not irradiated and acted as a control. Tissue
      generation, vascularity, cellular proliferation and apoptosis were investigated
      either 2 or 5 weeks after irradiation through micro-computed tomography,
      histomorphometry and real-time polymerase chain reaction (PCR). At 2 weeks after
      irradiation, tissue generation and central vascularity were significantly lower
      and apoptosis was significantly higher in groups II and III than group IV, but
      without signs of necrosis. Cellular proliferation was significantly lower in
      groups I and II. After 5 weeks, the irradiated groups showed improvement in all
      parameters in relation to the control group, indicating a retained capacity for
      angiogenesis after irradiation. PCR results confirmed the expression of
      osteogenesis-related genes in all irradiated groups. Dense collagen was detected
      5 weeks after irradiation, and one construct showed discrete islands of bone
      indicating a retained osteogenic capacity after irradiation. This demonstrates
      for the first time that axial vascularization was capable of supporting a
      synthetic bone construct after a high dose of irradiation that is comparable to
      adjuvant radiotherapy. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696710
TI  - The productivity limit of manufacturing blood cell therapy in scalable stirred
      bioreactors.
AB  - Manufacture of red blood cells (RBCs) from progenitors has been proposed as a
      method to reduce reliance on donors. Such a process would need to be extremely
      efficient for economic viability given a relatively low value product and high (2
      * 1012 ) cell dose. Therefore, the aim of these studies was to define the
      productivity of an industry standard stirred-tank bioreactor and determine
      engineering limitations of commercial red blood cells production. Cord blood
      derived CD34+ cells were cultured under erythroid differentiation conditions in a
      stirred micro-bioreactor (AmbrTM). Enucleated cells of 80% purity could be
      created under optimal physical conditions: pH 7.5, 50% oxygen, without gas
      sparging (which damaged cells) and with mechanical agitation (which directly
      increased enucleation). O2 consumption was low (~5 * 10-8  MUg/cell.h)
      theoretically enabling erythroblast densities in excess of 5 * 108 /ml in
      commercial bioreactors and sub-10 l/unit production volumes. The bioreactor
      process achieved a 24% and 42% reduction in media volume and culture time,
      respectively, relative to unoptimized flask processing. However, media exchange
      limited productivity to 1 unit of erythroblasts per 500 l of media. Systematic
      replacement of media constituents, as well as screening for inhibitory levels of
      ammonia, lactate and key cytokines did not identify a reason for this limitation.
      We conclude that the properties of erythroblasts are such that the conventional
      constraints on cell manufacturing efficiency, such as mass transfer and metabolic
      demand, should not prevent high intensity production; furthermore, this could be
      achieved in industry standard equipment. However, identification and removal of
      an inhibitory mediator is required to enable these economies to be realized.
      Copyright (c) 2016 The Authors Journal of Tissue Engineering and Regenerative
      Medicine Published by John Wiley & Sons Ltd.

PMID- 27696711
TI  - Ewing sarcoma family of tumors in children younger than 10 years of age.
AB  - AIM: Few data exist regarding the clinical characteristics and outcome of young
      children with Ewing sarcoma family of tumors (ESFT). METHODS: We reviewed the
      records of ESFT patients at our institution younger than 10 years of age at
      diagnosis. RESULTS: Forty-two patients were identified. Median age was 6.4 years
      (range 0.6-9.5 years). Most patients had T2 (>5 cm) tumors (n = 31; 74%). Most
      common primary site was the extremity (n = 17; 41%). Seven patients (17%) had
      metastasis at diagnosis. For local tumor control, 20 patients had surgery only,
      13 had radiation therapy only, and 6 had surgery plus radiation. Surgical margin
      status was negative in 19 patients (73%). Median follow-up was 4.7 years (range
      0.7-29.7 years), and 5-year relapse-free survival (RFS) and overall survival (OS)
      estimates were 67% (95% CI: 53-84%) and 82% (95% CI: 71-95%), respectively.
      Metastasis at presentation was the only significant predictor for decreased RFS
      (P = 0.008) and OS (P = 0.01). A trend was seen for T2 tumors with worse OS (P =
      0.09). CONCLUSION: Patients younger than 10 years of age with ESFT may have a
      better OS than older patients, but further study of a homogeneously treated
      larger cohort is needed.

PMID- 27696712
TI  - Enterovesical fistula as a result of neutropenic enterocolitis in a pediatric
      patient with acute leukemia.

PMID- 27696713
TI  - Mesenchymal stromal cells regulate the cell mobility and the immune response
      during osteogenesis through secretion of vascular endothelial growth factor A.
AB  - Cell-cell interaction is believed to play a critical role in the cell-based
      therapy for bone regeneration. However, the mechanisms involved in the
      interaction between donor cells and host cells during the bone healing process
      are still not clear. This study investigated the potential effect of vascular
      endothelial growth factor A (VEGFA) produced by osteogenically differentiated
      mesenchymal stem cells (O-MSCs) on the recruitment and regulation of
      undifferentiated MSCs and macrophages during osteogenesis. Factors secreted from
      MSCs during osteogenic differentiation were monitored by cytokine arrays.
      Indirect coculture models were applied to study the effect of VEGFA derived from
      O-MSCs on the motility, cell morphology and CXCL12/CXCR4 expression in MSCs as
      well as the regulation of local immune response. A mouse skull defect model was
      used to unveil the cell recruitment, macrophage activity and new bone formation
      following O-MSCs transplantation. It was found that VEGFA secretion increased
      dramatically during the osteogenic differentiation of MSCs. The secreted VEGFA by
      O-MSCs stimulated the expression of CXCL12/CXCR4, resulting in the recruitment of
      MSCs and macrophages to the bone defects. It was noted that O-MSCs could regulate
      the local inflammation by modulating the expression of proinflammatory cytokines
      in macrophages and neutralizing VEGFA produced by O-MSCs resulted in significant
      decrease of cell recruitment, cytokine secretion and new bone formation. This
      study demonstrates that VEGFA secreted by O-MSCs plays a pivotal role in the cell
      recruitment and regulation of local immune response during osteogenesis.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696715
TI  - Building an ARC to Grant Success: The Aims Review Committee.

PMID- 27696714
TI  - Investigation of multivalent interactions between conjugate of quantum dots with
      c-Myc peptide tag and the anti-c-Myc antibody by capillary electrophoresis with
      fluorescence detection.
AB  - Herein, we report an assay for detecting the binding of a multivalent peptide and
      antibody within a capillary with the use of fluorescence coupled capillary
      electrophoresis. Quantum dots and a c-Myc tag containing peptide EQKLISEEDLG4 H6
      were injected sequentially and formed a multivalent quantum dot-EQKLISEEDLG4 H6
      assembly within the capillary. The efficiency of the quantum dot-peptide self
      assembly was affected by the peptide/quantum dot molar ratio, sampling time, and
      interval time. Finally, the binding of the monoclonal anti-c-Myc antibody and the
      multivalent quantum dot-EQKLISEEDLG4 H6 ligand was studied using an in-capillary
      assay. The microscopic dissociation constant for the self-assembly of monoclonal
      anti-c-Myc antibody and quantum dot-EQKLISEEDLG4 H6 was determined to be 14.1 MUM
      with a stoichiometry of the peptide-antibody complex of 1.7 determined after
      fitting this to the Hill equation. This method can be further extended to detect
      a wide range of biomolecule-biomolecule binding interactions.

PMID- 27696716
TI  - In vitro evaluation of apoptotic effect of bis(acetylacetonato-k2 O,O')(1,10
      phenanthroline-k2  N,N')Zn(II) complex.
AB  - Phenanthroline derivatives have been reported as potential bioactive compounds
      because of their ability to interact with DNA. To evaluate the antiproliferative
      effect of bis(acetylacetonate-k2 O,O)(1,10-phenanthroline-k2 N,N)Zn(II) or
      Zn(acac)2 (phen) complex, the compound was obtained in a simple manner and
      further characterized to determine crystal structure, thermal behavior,
      morphology, and spectroscopic properties. The structure of the complex was
      confirmed by X-ray single structure as well as by 1H and 13C nuclear magnetic
      resonance (NMR) in dmso-d6 (dimethyl sulfoxide) solution and in the solid state
      by 13C CP/MAS. Although preparation of this compound has been described
      previously, there are no reports on its biological activity; here, we assessed
      its antiproliferative effect on fibroblasts, A253, FaDu, Cal-27, RH-30, RD, U
      373, C6, A-549, MDA-MB-231, and MCF-7 cancer cell lines at different doses (50
      100 and 150 MUg/ml). The cell viability was determined by MTT assay and high
      activity was observed for the most of the cell lines, and TUNEL results showed
      the induction of apoptosis.

PMID- 27696717
TI  - Non-Newtonian versus numerical rheology: Practical impact of shear-thinning on
      the prediction of stable and unstable flows in intracranial aneurysms.
AB  - Computational fluid dynamics (CFD) shows promise for informing treatment planning
      and rupture risk assessment for intracranial aneurysms. Much attention has been
      paid to the impact on predicted hemodynamics of various modelling assumptions and
      uncertainties, including the need for modelling the non-Newtonian, shear-thinning
      rheology of blood, with equivocal results. Our study clarifies this issue by
      contextualizing the impact of rheology model against the recently demonstrated
      impact of CFD solution strategy on the prediction of aneurysm flow instabilities.
      Three aneurysm cases were considered, spanning a range of stable to unstable
      flows. Simulations were performed using a high-resolution/accuracy solution
      strategy with Newtonian and modified-Cross rheology models and compared against
      results from a so-called normal-resolution strategy. Time-averaged and
      instantaneous wall shear stress (WSS) distributions, as well as frequency content
      of flow instabilities and dome-averaged WSS metrics, were minimally affected by
      the rheology model, whereas numerical solution strategy had a demonstrably more
      marked impact when the rheology model was fixed. We show that point-wise
      normalization of non-Newtonian by Newtonian WSS values tended to artificially
      amplify small differences in WSS of questionable physiological relevance in
      already-low WSS regions, which might help to explain the disparity of opinions in
      the aneurysm CFD literature regarding the impact of non-Newtonian rheology.
      Toward the goal of more patient-specific aneurysm CFD, we conclude that attention
      seems better spent on solution strategy and other likely "first-order" effects
      (eg, lumen segmentation and choice of flow rates), as opposed to "second-order"
      effects such as rheology.

PMID- 27696718
TI  - Adolescent deliberate self-poisoning in South-East Melbourne.
AB  - OBJECTIVE: To describe the characteristics of adolescents presenting with
      deliberate self-poisoning (DSP) to a large Australian healthcare network. METHOD:
      This is a retrospective chart review of 12-17 year olds presenting to three
      Monash Health EDs with self-poisoning from January 2012 to December 2014.
      RESULTS: There were 35 207 adolescent presentations in the study period. A total
      of 721 cases were for DSP (2%), and 501 (1.4%) presented with recreational or
      accidental self-poisoning. The most common DSP toxicants were paracetamol (28%),
      non-steroidal anti-inflammatory agents (15%) and serotonin reuptake inhibitors
      (10%). Of the DSP presentations, 96% were impulsive events; 23% of patients (n =
      129) presented on multiple occasions, and 67% of all DSP cases had a past
      psychiatric history, particularly depression (57%). Disposition for DSP patients
      included 60% discharged home, 6% short stay unit, 19% medical admission, 13%
      psychiatric admission and 2% intensive care unit admission. There were no
      mortalities. CONCLUSION: Adolescent DSP presentations frequently involved
      impulsive ingestion of over-the-counter medications, suggesting less access to
      prescription medications. Additionally, pre-existing mental health history and re
      presentation were common. Initiatives to prevent DSP might include an increased
      focus on the early identification and management of mental health problems in
      adolescents in the community.

PMID- 27696719
TI  - BK polyomavirus encephalitis in a patient with thrombotic microangiopathy after
      an allogeneic hematopoietic stem cell transplant.
AB  - To date, only one case of BK polyomavirus (BKPyV) encephalitis combined with
      transplant-associated thrombotic microangiopathy has been reported in an
      hematopoietic stem cell transplantation (HCT) recipient. We report the case of an
      HCT recipient who developed thrombotic microangiopathy and subsequent BKPyV
      encephalitis. She died despite treatment with cidofovir, ciprofloxacin, and
      intravenous immunoglobulin without improvement in mental status. Early suspicion
      of BKPyV encephalitis in an HCT recipient presenting with altered mental status
      and hemorrhagic cystitis is important.

PMID- 27696721
TI  - Metabolic profiling of recombinant Escherichia coli cultivations based on high
      throughput FT-MIR spectroscopic analysis.
AB  - Escherichia coli is one of the most used host microorganism for the production of
      recombinant products, such as heterologous proteins and plasmids. However,
      genetic, physiological and environmental factors influence the plasmid
      replication and cloned gene expression in a highly complex way. To control and
      optimize the recombinant expression system performance, it is very important to
      understand this complexity. Therefore, the development of rapid, highly sensitive
      and economic analytical methodologies, which enable the simultaneous
      characterization of the heterologous product synthesis and physiologic cell
      behavior under a variety of culture conditions, is highly desirable. For that,
      the metabolic profile of recombinant E. coli cultures producing the pVAX-lacZ
      plasmid model was analyzed by rapid, economic and high-throughput Fourier
      Transform Mid-Infrared (FT-MIR) spectroscopy. The main goal of the present work
      is to show as the simultaneous multivariate data analysis by principal component
      analysis (PCA) and direct spectral analysis could represent a very interesting
      tool to monitor E. coli culture processes and acquire relevant information
      according to current quality regulatory guidelines. While PCA allowed capturing
      the energetic metabolic state of the cell, e.g. by identifying different C
      sources consumption phases, direct FT-MIR spectral analysis allowed obtaining
      valuable biochemical and metabolic information along the cell culture, e.g.
      lipids, RNA, protein synthesis and turnover metabolism. The information achieved
      by spectral multivariate data and direct spectral analyses complement each other
      and may contribute to understand the complex interrelationships between the
      recombinant cell metabolism and the bioprocess environment towards more economic
      and robust processes design according to Quality by Design framework. (c) 2016
      American Institute of Chemical Engineers Biotechnol. Prog., 33:285-298, 2017.

PMID- 27696722
TI  - Development and validation of a capillary electrophoresis method for the
      characterization of sulfoethyl cellulose.
AB  - To characterize sulfoethyl cellulose el samples, a capillary electrophoresis
      method was developed and validated sulfoethyl cellulose el was hydrolyzed, and
      the resulting d-glucose derivatives were analyzed after reductive amination with
      4-aminobenzoic acid using 150 mM boric acid, pH 9.5, as background electrolyte at
      20 degrees C and a voltage of 28 kV. Peak identification was derived from
      capillary electrophoresis with mass spectrometry using 25 mM ammonia adjusted to
      pH 6.2 by acetic acid as electrolyte. Besides mono-, di-, and trisulfoethyl d
      glucose small amounts of disaccharides could be identified resulting from
      incomplete hydrolysis. The linearity of the borate buffer-based capillary
      electrophoresis method was evaluated using d-glucose in the concentration range
      of 3.9-97.5 MUg/mL, while limits of detection and quantification derived from the
      signal-to-noise ratio of 3 and 10 were 0.4 +/- 0.1 and 1.2 +/- 0.3 MUg/mL,
      respectively. Reproducibility and intermediate precision were determined using a
      hydrolyzed sulfoethyl cellulose el sample and ranged between 0.2 and 8.8% for
      migration times and between 0.3 and 10.4% for peak area. The method was applied
      to the analysis of the degree of substitution of synthetic sulfoethyl cellulose
      el samples obtained by variation of the synthetic process and compared to data
      obtained by elemental analysis.

PMID- 27696720
TI  - Association of prenatal lipid-based nutritional supplementation with fetal growth
      in rural Gambia.
AB  - Prenatal supplementation with protein-energy (PE) and/or multiple-micronutrients
      (MMNs) may improve fetal growth, but trials of lipid-based nutritional
      supplements (LNSs) have reported inconsistent results. We conducted a post-hoc
      analysis of non-primary outcomes in a trial in Gambia, with the aim to test the
      associations of LNS with fetal growth and explore how efficacy varies depending
      on nutritional status. The sample comprised 620 pregnant women in an individually
      randomized, partially blinded trial with four arms: (a) iron and folic acid
      (FeFol) tablet (usual care, referent group), (b) MMN tablet, (c) PE LNS, and (d)
      PE + MMN LNS. Analysis of variance examined unadjusted differences in fetal
      biometry z-scores at 20 and 30 weeks and neonatal anthropometry z-scores, while
      regression tested for modification of intervention-outcome associations by season
      and maternal height, body mass index, and weight gain. Despite evidence of
      between-arm differences in some fetal biometry, z-scores at birth were not
      greater in the intervention arms than the FeFol arm (e.g., birth weight z-scores:
      FeFol -0.71, MMN -0.63, PE -0.64, PE + MMN -0.62; group-wise p = .796). In
      regression analyses, intervention associations with birth weight and head
      circumference were modified by maternal weight gain between booking and 30 weeks
      gestation (e.g., PE + MMN associations with birth weight were +0.462 z-scores
      (95% CI [0.097, 0.826]) in the highest quartile of weight gain but -0.099 z
      scores (-0.459, 0.260) in the lowest). In conclusion, we found no strong evidence
      that a prenatal LNS intervention was associated with better fetal growth in the
      whole sample.

PMID- 27696723
TI  - Use of negative pressure wound therapy on malignant wounds - a case report and
      review of literature.
AB  - The presence of malignancy is considered a contraindication to the use of
      negative pressure wound therapy (NPWT) because of concerns that it may promote
      tumourigenesis and expedite metastasis. This notion is extrapolated from studies
      evaluating NPWT in normal tissues. Despite the absence of direct evidence, the
      use of this technology in malignant wounds is widely considered a
      contraindication. We present the case of a patient with treatment-resistant
      metastatic colon cancer, who developed a chronic abdominal wound with positive
      margins. A staged reconstruction using NPWT was performed and wound closure
      allowed the patient to meet eligibility criteria and enrol in a clinical trial
      for treatment of his oncological disease. Skin closure remained intact until the
      patient expired 6 months after the wound closure. This case, as well as others in
      the literature, demonstrated that the use of NPWT should not be considered an
      absolute contraindication in malignancy. Individualised approaches taking into
      account the patient's clinical scenario, the available evidence, as well as the
      risks and benefits of this technology are recommended.

PMID- 27696725
TI  - Integrated Exploitation of the Structural Diversity Space of Chemotherapy Drugs
      to Selectively Inhibit HER2 T798M Mutant in Lung Cancer.
AB  - An acquired T798M gatekeeper mutation in human epidermal growth factor receptor 2
      (HER2) kinase can cause drug resistance to anti-HER2 chemotherapy drugs in lung
      cancer. Previously, the reversible pan-kinase inhibitor staurosporine has been
      found to selectively inhibit the HER2 T798M mutant over wild-type kinase,
      suggesting that the staurosporine scaffold is potentially to develop mutant
      selective inhibitors. Here, we systematically evaluated the chemical space of
      staurosporine scaffold-based compounds in response to HER2 T798M mutation at
      structural, energetic and molecular levels by using an integrated analysis
      strategy. With this strategy, we were able to identify several novel wild-type
      sparing inhibitors with high or moderate selectivity, which are comparable to or
      even better than that of the parent compound staurosporine. Molecular modeling
      and structural analysis revealed that noncovalent contacts can form between the
      side chain of mutated residue Met798 and selective inhibitor ligands, which may
      improve the favorable interaction energy between the kinase and inhibitor and
      reduce the unfavorable desolvation penalty upon the kinase-inhibitor binding.

PMID- 27696724
TI  - Comparative Assessment of the Different American College of Rheumatology/European
      League Against Rheumatism Remission Definitions for Rheumatoid Arthritis for
      Their Use as Clinical Trial End Points.
AB  - OBJECTIVE: The American College of Rheumatology (ACR) and the European League
      Against Rheumatism (EULAR) have defined remission using Boolean- or index-based
      criteria (i.e., a Simplified Disease Activity Index [SDAI] score of <=3.3). We
      undertook this study to compare definitions of remission to inform choice of end
      points for future rheumatoid arthritis (RA) clinical trials, and we also included
      in our comparison the remission criterion of a score of <=2.8 on the Clinical
      Disease Activity Index (CDAI). METHODS: We performed post hoc analyses on
      clinical remission rates using data from 2 infliximab trials (the ASPIRE [Active
      Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid
      Arthritis of Early Onset] and ATTRACT [Anti-Tumor Necrosis Factor Trial in
      Rheumatoid Arthritis with Concomitant Therapy] trials) and 1 golimumab trial (the
      GO-FORWARD trial). We investigated stringency of the different remission
      definitions, their power to discriminate between active drug and comparator, and
      aspects of their internal and external validity. We also investigated population
      determinants of discriminatory power for a particular remission end point.
      RESULTS: In patients with early RA (the ASPIRE trial), ACR/EULAR Boolean, CDAI,
      and SDAI remission rates at 6-7 months were 4-6% for methotrexate (MTX) alone
      versus 11-14% for infliximab plus MTX. In patients with MTX-refractory active RA
      (the ATTRACT and GO-FORWARD trials), remission rates were <=1% for comparator
      (add-on of placebo) versus 4-6% for add-on of infliximab in the ATTRACT trial and
      <=3% for comparator (add-on of placebo) versus 11-13% for add-on of golimumab in
      the GO-FORWARD trial. Existing remission cut points of different measures were
      generally comparable, with the Boolean criteria being somewhat more stringent
      than the SDAI and CDAI criteria. Remission rates were similar across definitions,
      as was average statistical power (CDAI, 55.6%; Boolean, 59.9%; SDAI, 62.6%).
      CONCLUSION: Remission is an ambitious primary end point for RA clinical trials,
      to be reserved for selected scenarios based on power considerations. The
      ACR/EULAR definitions are interchangeable, with slightly higher stringency of
      Boolean criteria over index-based criteria.

PMID- 27696726
TI  - Parathyroid adenoma: a comprehensive biochemical and histological correlative
      study.
AB  - OBJECTIVE: To investigate the controversial relationship between preoperative
      calcium and parathyroid hormone levels and the dimensions and histological
      features of parathyroid adenoma in patients with primary hyperparathyroidism.
      STUDY DESIGN: Historical cohort. SETTING: Tertiary medical centre. SUBJECTS AND
      METHODS: Clinical and tumour-related data were collected from the medical files
      of all patients who underwent parathyroidectomy for primary hyperparathyroidism
      in 1996-2012. Preoperative blood parathyroid hormone and calcium levels and urine
      calcium levels were correlated with the size, weight and volume of the
      parathyroid adenoma. Pathohistological features were determined in a
      representative sample of archived paraffin-embedded sections and analysed by
      calcium or parathyroid hormone level (high/low) and adenoma weight (high/low).
      RESULTS: A total of 378 patients were included. There was a statistically
      significant direct correlation of preoperative calcium and parathyroid hormone
      levels with tumour dimensions and of tumour weight and chief-cell percentage. At
      a preoperative calcium level >11.5 mg/dL and parathyroid hormone (PTH) level >165
      mg/dL, we predict that the adenoma would measure more than 2.7 g, 2.18 cm and
      volume of 3.59 cm3 . CONCLUSIONS: In patients with primary hyperparathyroidism,
      preoperative calcium and PTH levels may be predictive of parathyroid adenoma
      dimensions.

PMID- 27696727
TI  - Early Disease Activity or Clinical Response as Predictors of Long-Term Outcomes
      With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis.
AB  - OBJECTIVE: Early identification of patients unlikely to achieve good long-term
      disease control with anti-tumor necrosis factor therapy in axial
      spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians
      following treat-to-target recommendations. Here we assess associations between
      disease activity or clinical response during the first 12 weeks of treatment and
      attainment of treatment targets at week 48 in axial SpA and PsA patients
      receiving certolizumab pegol. METHODS: The relationship between disease activity
      or clinical response during the first 12 weeks of treatment and achievement of
      week-48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis
      Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level, or Bath
      Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for
      PsA: minimal disease activity) was assessed post hoc using RAPID-axSpA and RAPID
      PsA trial data. RESULTS: A clear relationship between disease activity from week
      2 to 12 and achievement of week-48 treatment targets was observed in both axial
      SpA and PsA populations. In axial SpA, week-48 ASDAS inactive disease was
      achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at
      week 12, compared to 68% of patients (34 of 50) with week-12 ASDAS inactive
      disease. For PsA, week-48 minimal disease activity was achieved by 0% of patients
      (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level
      >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28-CRP <2.6.
      Similar results were observed regardless of the disease activity measure used.
      Clinical response at week 12 also predicted week-48 outcomes, though to a lesser
      extent than disease activity. CONCLUSION: Using disease activity and the clinical
      response state during the first 12 weeks of certolizumab pegol treatment, it was
      possible to identify a subset of axial SpA and PsA patients unlikely to achieve
      long-term treatment goals.

PMID- 27696728
TI  - Association of Beta-Blocker Use With Less Prevalent Joint Pain and Lower Opioid
      Requirement in People With Osteoarthritis.
AB  - OBJECTIVE: Recent findings suggest that beta-adrenergic blockers have
      antinociceptive properties. The aim of this study was to compare levels of large
      joint pain between those taking adrenergic blockers and those taking other
      antihypertensive medications. METHODS: Data from the Genetics of Osteoarthritis
      and Lifestyle (GOAL) study, a secondary-care cohort of osteoarthritis (OA)
      patients, were used. Joint pain was assessed using Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) pain scores in 873 individuals with
      symptomatic hip and/or knee OA and hypertension, who were taking >=1 prescription
      antihypertensive medications. The association between adrenergic blocker
      prescription and at least moderate joint pain (WOMAC score <75) and use of
      prescription analgesics was examined using binary logistic regression. Analyses
      were adjusted for age, sex, body mass index, knee or hip OA, history of joint
      replacement (at other joints), anxiety, and depression. RESULTS: The use of beta
      adrenergic blockers was associated with lower WOMAC pain scores and with a lower
      prevalence of joint pain after adjustment for demographic variables and
      comorbidity (adjusted odds ratio [ORadj ] for pain 0.68 [95% confidence interval
      (95% CI) 0.51, 0.92]; P < 0.011). No associations with pain were observed with
      use of alpha-blockers (ORadj for pain 0.94 [95% CI 0.55, 1.58]) or with any other
      class of antihypertensive medications. Prescription of beta-blockers was also
      associated negatively with opioid use (ORadj for opioids 0.73 [95% CI 0.54,
      0.98]; P < 0.037) and with the use of prescription analgesics in general (ORadj
      for analgesics 0.74 [95% CI 0.56, 0.94]; P < 0.032). CONCLUSION: The use of beta
      blockers is associated with less joint pain and a lower use of opioids and other
      analgesics in individuals with symptomatic large-joint OA. This observation needs
      to be confirmed by other studies.

PMID- 27696729
TI  - Glass slides functionalized by 1-carboxyethyl-3-methylimidazolium chloride for
      the determination of triazine herbicides in rice using high-performance liquid
      chromatography.
AB  - A novel and simple supported ionic-liquid-based solid-phase extraction method for
      the determination of triazine herbicides in rice was developed. Glass slides were
      functionalized by an ionic liquid, 1-carboxyethyl-3-methylimidazolium chloride,
      and were used for the simultaneous extraction of seven triazine herbicides in
      rice samples. The effects of the type of extraction solvent, the extraction time,
      the type and volume of loading solvent, and the type of eluting solvent on the
      extraction efficiency were investigated and optimized. Under the optimum
      operation conditions, the limits of detection for seven triazine herbicides in
      rice samples obtained by high-performance liquid chromatography were 3.16-5.42
      ng/g, which were lower than the maximum residue levels established by various
      organizations. The linear correlation coefficients were higher than 0.9975 in the
      concentration range of 0.015-1.08 MUg/g for the seven triazine herbicides. The
      recoveries of the seven triazine herbicides at the two concentration levels of
      0.15 and 0.45 MUg/g are between 82.47 and 104.21%, with relative standard
      deviations of 0.69-9.19%. The intra- and inter-day (n = 5) precisions for all
      triazine herbicides at the spiked level of 0.30 MUg/g were 1.72-11.71%.

PMID- 27696730
TI  - The future of heart valve replacement: recent developments and translational
      challenges for heart valve tissue engineering.
AB  - Heart valve replacement is often the only solution for patients suffering from
      valvular heart disease. However, currently available valve replacements require
      either life-long anticoagulation or are associated with valve degeneration and
      calcification. Moreover, they are suboptimal for young patients, because they do
      not adapt to the somatic growth. Tissue-engineering has been proposed as a
      promising approach to fulfil the urgent need for heart valve replacements with
      regenerative and growth capacity. This review will start with an overview on the
      currently available valve substitutes and the techniques for heart valve
      replacement. The main focus will be on the evolution of and different approaches
      for heart valve tissue engineering, namely the in vitro, in vivo and in situ
      approaches. More specifically, several heart valve tissue-engineering studies
      will be discussed with regard to their shortcomings or successes and their
      possible suitability for novel minimally invasive implantation techniques. As in
      situ heart valve tissue engineering based on cell-free functionalized starter
      materials is considered to be a promising approach for clinical translation, this
      review will also analyse the techniques used to tune the inflammatory response
      and cell recruitment upon implantation in order to stir a favourable outcome:
      controlling the blood-material interface, regulating the cytokine release, and
      influencing cell adhesion and differentiation. In the last section, the authors
      provide their opinion about the future developments and the challenges towards
      clinical translation and adaptation of heart valve tissue engineering for valve
      replacement. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696731
TI  - Incidence and Management of Cardiovascular Risk Factors in Psoriatic Arthritis
      and Rheumatoid Arthritis: A Population-Based Study.
AB  - OBJECTIVE: To examine the prevalence and incidence of cardiovascular (CV) risk
      factors, including hypertension, hyperlipidemia, diabetes mellitus (DM), and
      obesity among patients with psoriatic arthritis (PsA) and rheumatoid arthritis
      (RA) compared to the general population, and to examine the treatment of incident
      CV risk factors in PsA and RA compared to controls. METHODS: A cohort study was
      conducted within The Health Improvement Network, a medical record database in the
      UK, using data from 1994 to 2014. Patients ages 18-89 years with PsA or RA were
      matched to controls on practice and start date. The prevalence and incidence of
      CV risk factors identified by diagnostic codes were calculated. Cox proportional
      hazards models were used to examine the relative incidence of these CV risk
      factors. Finally, pharmacologic therapies for incident CV risk factors were
      examined. RESULTS: Study subjects included patients with PsA (n = 12,548), RA (n
      = 53,215), and controls (n = 389,269). The prevalence of all CV risk factors was
      significantly elevated in PsA. Only the prevalence of DM and obesity was
      increased in RA. Incidence of hypertension, hyperlipidemia, and DM was elevated
      in PsA and RA. Receipt of therapy within 1 year following incident diagnosis of
      CV risk factors was not substantially different between the groups; approximately
      85%, 65%, and 45% of patients received prescriptions for hypertension,
      hyperlipidemia, and DM, respectively. CONCLUSION: Patients with PsA have an
      increased prevalence of CV risk factors, and both patients with PsA and patients
      with RA have increased incidence of a new diagnosis of CV risk factors.
      Pharmacologic treatment of CV risk factors in patients with PsA and RA was
      similar to controls in the UK.

PMID- 27696732
TI  - Do Short and Sustained Periods of American College of Rheumatology/European
      League Against Rheumatism Remission Predict Functional and Radiographic Outcome
      in Early Rheumatoid Arthritis Patients With Low Overall Damage Progression?
AB  - OBJECTIVE: To investigate whether remission at single and consecutive visits
      predicts good outcome in early rheumatoid arthritis (RA). METHODS: The presence
      of remission according to American College of Rheumatology (ACR)/European League
      Against Rheumatism (EULAR) and other criteria (Boolean clinical, Clinical Disease
      Activity Index, Disease Activity Score [DAS], DAS in 28 joints, and Routine
      Assessment of Patient Index Data 3) was assessed in early RA patients during the
      first year of the Combination Therapy for Rheumatoid Arthritis light trial.
      Likelihood ratios were used to assess whether meeting the remission criteria at
      single visits (13, 26, 39, or 52 weeks) and consecutive visits (13 and 26, 26 and
      39, or 39 and 52 weeks) predicted good outcome in the second year (52-104 weeks).
      Good outcome was defined for function (Health Assessment Questionnaire score
      consistently <=0.5 and no deterioration), radiographic damage progression (no
      deterioration in Sharp/van der Heijde scores), and both ("overall good outcome").
      RESULTS: Of the original 164 trial patients, 144 had evaluable data. In the
      second year, good functional outcome was observed in 35%, good radiographic
      outcome in 79%, and both in 28% of the patients. Almost all criteria predicted
      good functional and good overall outcome, at both single and consecutive visits;
      only single DAS remission did not significantly predict good overall outcome (P =
      0.07). Sustained remission periods resulted in higher likelihood ratios than
      remission at single visits. None of the criteria predicted good radiographic
      outcome. CONCLUSION: Early RA patients who reached remission according to
      ACR/EULAR and other criteria during short or sustained periods were likely to
      retain good physical function in the subsequent months. Sustained remission
      periods were a stronger predictor than remission at single visits. However, in
      the setting of low overall damage progression, (sustained) remission was not
      predictive of good radiographic outcome.

PMID- 27696733
TI  - Identification of LmUAP1 as a 20-hydroxyecdysone response gene in the chitin
      biosynthesis pathway from the migratory locust, Locusta migratoria.
AB  - In Locusta migratoria, we found that two chitin biosynthesis genes, UDP N
      acetylglucosamine pyrophosphorylase gene LmUAP1 and chitin synthase gene LmCHS1,
      are expressed mainly in the integument and are responsible for cuticle formation.
      However, whether these genes are regulated by 20-hydroxyecdysone (20E) is still
      largely unclear. Here, we showed the developmental expression pattern of LmUAP1,
      LmCHS1 and the corresponding 20E titer during the last instar nymph stage of
      locust. RNA interference (RNAi) directed toward a common region of the two
      isoforms of LmEcR (LmEcRcom) reduced the expression level of LmUAP1, while there
      was no difference in the expression of LmCHS1. Meantime, injection of 20E in vivo
      induced the expression of LmUAP1 but not LmCHS1. Further, we found injection
      based RNAi of LmEcRcom resulted in 100% mortality. The locusts failed to molt
      with no apolysis, and maintained in the nymph stage until death. In conclusion,
      our preliminary results indicated that LmUAP1 in the chitin biosynthesis pathway
      is a 20E late-response gene and LmEcR plays an essential role in locust growth
      and development, which could be a good potential target for RNAi-based pest
      control.

PMID- 27696734
TI  - Synthesis and evaluation of anti-inflammatory properties of silver nanoparticle
      suspensions in experimental colitis in mice.
AB  - The aim of our study was to investigate the effect of newly developed silver
      nanoparticle aqueous suspensions NanoAg1 and NanoAg2 in the mouse models
      mimicking ulcerative colitis and Crohn's disease. NanoAg1 and NanoAg2 were
      synthesized in aqueous medium with the involvement of tannic acid. To elucidate
      their anti-inflammatory activity, semi-chronic mouse models of inflammation
      induced by dextrane sulfate sodium addition to drinking water and intracolonic
      (i.c.) administration of 2,4,6-trinitrobenzenesulfonic acid were used. NanoAg1
      and NanoAg2 (500 mg/dm3, 100 MUl/animal, i.c., once daily) significantly
      ameliorated colitis in dextrane sulfate sodium- and 2,4,6-trinitrobenzenesulfonic
      acid-induced mouse models of colonic inflammation, as indicated by reduced
      macroscopic, ulcer and microscopic scores. The anti-inflammatory effect was
      dependent on the shape and diameter of silver nanoparticles, as indicated by
      weaker effect of NanoAg1 than NanoAg2. In addition, administration of NanoAg2,
      but not NanoAg1, modulated colonic microbiota, as indicated by reduced number of
      Escherichia coli and Clostridium perfringens, and increased number of
      Lactobacillus sp. Summarizing, NanoAg1 and NanoAg2 after administered i.c.
      effectively alleviate colitis in experimental models of ulcerative colitis and
      Crohn's disease in mice. Therefore, NanoAg1 and NanoAg2 administered i.c. have
      the potential to become valuable agents for the treatment of inflammatory bowel
      diseases.

PMID- 27696735
TI  - Eight-Year Retention Rate of First-Line Tumor Necrosis Factor Inhibitors in
      Spondyloarthritis: A Multicenter Retrospective Analysis.
AB  - OBJECTIVE: To evaluate the 8-year survival of the first tumor necrosis factor
      inhibitor (TNFi) in patients with axial spondyloarthritis (SpA) or psoriatic
      arthritis (PsA), identify the predictive factors for withdrawal, and compare the
      discontinuation rates for infliximab, etanercept, and adalimumab. METHODS: We
      evaluated PsA and axial SpA patients treated with a first-line TNFi between 2005
      and 2015 at 4 Italian tertiary centers. Eight-year drug survival was calculated
      by the Kaplan-Meier method, and risk for discontinuation among treatment groups
      compared by stratified log-rank test. Univariate and multivariate Cox
      proportional hazard models were developed to examine predictors of withdrawal.
      RESULTS: Of 614 patients (316 axial with SpA, 298 with PsA), 203 received
      adalimumab, 131 etanercept, and 280 infliximab, with similar frequencies in axial
      SpA and PsA subgroups. The cumulative 8-year retention rate in the whole
      population was 55.1% (57.2% and 51.9% for axial SpA and PsA, respectively; P =
      not significant). No significant differences were observed in drug persistence
      among individual TNFi in either group. Male sex (hazard ratio [HR] 0.595 [95%
      confidence interval (95% CI) 0.405-0.875]; P = 0.008) and concomitant
      methotrexate use (HR 0.648 [95% CI 0.426-0.985]; P = 0.042) were associated with
      a lower risk of withdrawal in PsA. High baseline Bath Ankylosing Spondylitis
      Disease Activity Index (HR 0.9842 [95% CI 0.9708-0.9980]; P = 0.028) was
      associated with a lower risk of withdrawal in axial SpA. No difference was found
      in the comparative analysis of reasons for discontinuation between PsA and axial
      SpA. CONCLUSION: We reported that the real-life 8-year retention rate of the
      first TNFi in axial SpA and PsA is greater than 50%, with no significant
      differences between axial SpA and PsA, irrespective of the individual TNFi.

PMID- 27696736
TI  - The impact of personality on person-centred care: a study of care staff in
      Swedish nursing homes.
AB  - AIM AND OBJECTIVE: In this study, we explore how personal and situational factors
      relate to the provision of person-centred care (PCC) in nursing homes.
      Specifically, we focus on the relationship between the care staff's personality
      traits and provision of PCC and to what extent perceptions of the working
      environment influences this relationship. BACKGROUND: The ultimate goal of
      elderly care is to meet the older person's needs and individual preferences
      (PCC). Interpersonal aspects of care and the quality of relationship between the
      care staff and the older person are therefore central in PCC. DESIGN AND METHODS:
      A cross-sectional Swedish sample of elderly care staff (N = 322) completed an
      electronic survey including measures of personality (Mini-IPIP) and person
      centred care (Individualized Care Inventory, ICI). A principal component analysis
      was conducted on the ICI-data to separate the user orientation (process quality)
      of PCC from the preconditions (structure quality) of PCC. RESULTS: Among the five
      factors of personality, neuroticism was the strongest predictor of ICI user
      orientation. ICI preconditions significantly mediated this relationship,
      indicating the importance of a supportive working environment. In addition,
      stress was introduced as a potential explanation and was shown to mediate the
      impact of neuroticism on ICI preconditions. CONCLUSIONS: Personality traits have
      a significant impact on user orientation, and the perception of a supportive and
      stress free working environment is an important prerequisite for achieving high
      quality person-centred elderly care. IMPLICATIONS FOR PRACTICE: Understanding how
      personality is linked to the way care staff interacts with the older person adds
      a new perspective on provision of person-centred elderly care.

PMID- 27696738
TI  - Transcriptome analysis of sugar beet root maggot (Tetanops myopaeformis) genes
      modulated by the Beta vulgaris host.
AB  - Sugar beet root maggot (SBRM, Tetanops myopaeformis von Roder) is a major but
      poorly understood insect pest of sugar beet (Beta vulgaris L.). The molecular
      mechanisms underlying plant defense responses are well documented, however,
      little information is available about complementary mechanisms for insect
      adaptive responses to overcome host resistance. To date, no studies have been
      published on SBRM gene expression profiling. Suppressive subtractive
      hybridization (SSH) generated more than 300 SBRM ESTs differentially expressed in
      the interaction of the pest with a moderately resistant (F1016) and a susceptible
      (F1010) sugar beet line. Blast2GO v. 3.2 search indicated that over 40% of the
      differentially expressed genes had known functions, primarily driven by fruit fly
      D. melanogaster genes. Expression patterns of 18 selected EST clones were
      confirmed by RT-PCR analysis. Gene Ontology (GO) analysis predicted a dominance
      of metabolic and catalytic genes involved in the interaction of SBRM with its
      host. SBRM genes functioning during development, regulation, cellular process,
      signaling and under stress conditions were annotated. SBRM genes that were common
      or unique in response to resistant or susceptible interactions with the host were
      identified and their possible roles in insect responses to the host are
      discussed.

PMID- 27696737
TI  - Highly polygenic architecture of antidepressant treatment response: Comparative
      analysis of SSRI and NRI treatment in an animal model of depression.
AB  - Response to antidepressant (AD) treatment may be a more polygenic trait than
      previously hypothesized, with many genetic variants interacting in yet unclear
      ways. In this study we used methods that can automatically learn to detect
      patterns of statistical regularity from a sparsely distributed signal across
      hippocampal transcriptome measurements in a large-scale animal pharmacogenomic
      study to uncover genomic variations associated with AD. The study used four
      inbred mouse strains of both sexes, two drug treatments, and a control group
      (escitalopram, nortriptyline, and saline). Multi-class and binary classification
      using Machine Learning (ML) and regularization algorithms using iterative and
      univariate feature selection methods, including InfoGain, mRMR, ANOVA, and Chi
      Square, were used to uncover genomic markers associated with AD response.
      Relevant genes were selected based on Jaccard distance and carried forward for
      gene-network analysis. Linear association methods uncovered only one gene
      associated with drug treatment response. The implementation of ML algorithms,
      together with feature reduction methods, revealed a set of 204 genes associated
      with SSRI and 241 genes associated with NRI response. Although only 10% of genes
      overlapped across the two drugs, network analysis shows that both drugs modulated
      the CREB pathway, through different molecular mechanisms. Through careful
      implementation and optimisations, the algorithms detected a weak signal used to
      predict whether an animal was treated with nortriptyline (77%) or escitalopram
      (67%) on an independent testing set. The results from this study indicate that
      the molecular signature of AD treatment may include a much broader range of
      genomic markers than previously hypothesized, suggesting that response to
      medication may be as complex as the pathology. The search for biomarkers of
      antidepressant treatment response could therefore consider a higher number of
      genetic markers and their interactions. Through predominately different molecular
      targets and mechanisms of action, the two drugs modulate the same Creb1 pathway
      which plays a key role in neurotrophic responses and in inflammatory processes.
      (c) 2016 The Authors. American Journal of Medical Genetics Part B:
      Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

PMID- 27696739
TI  - Seven-Year Outcomes of the Silicone Arthroplasty in Rheumatoid Arthritis
      Prospective Cohort Study.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) causes destruction of the
      metacarpophalangeal (MCP) joints, leading to hand deformities, pain, and loss of
      function. This study prospectively assessed long-term functional and health
      related quality-of-life outcomes in RA patients with severe deformity at the MCP
      joints. METHODS: RA patients between ages 18 to 80 years with severe deformity at
      the MCP joints were referred to 1 of the 3 study sites. Subjects who elected to
      undergo silicone metacarpophalangeal joint arthroplasty (SMPA) while continuing
      with medical management were followed in the SMPA cohort. Subjects who elected to
      continue with medical management alone without surgery were followed in the non
      SMPA cohort. Objective measurements included grip and pinch strength as well as
      arc of motion, ulnar drift, and extensor lag of the MCP joints. Patient-reported
      outcomes included the Michigan Hand Questionnaire (MHQ) and the Arthritis Impact
      Measurement Scales questionnaire. Radiographs of SMPA implants were assessed and
      graded as intact, deformed, or fractured. RESULTS: MHQ scores showed large
      improvements post-SMPA, and baseline-adjusted expected outcomes in the SMPA group
      were significantly better at year 7 in function, aesthetics, satisfaction, and
      overall score compared to non-SMPA. SMPA subjects did not improve in grip or
      pinch strength, but achieved significant improvement and maintained the
      improvement long term in ulnar drift and extensor lag. CONCLUSION: Benefits of
      the SMPA procedure are maintained over 7 years with low rates of implant fracture
      or deformity. Non-SMPA patients remained stable in their hand function over the 7
      year study duration.

PMID- 27696740
TI  - Exploring the relationship between cortical GABA concentrations, auditory gamma
      band responses and development in ASD: Evidence for an altered maturational
      trajectory in ASD.
AB  - Autism spectrum disorder (ASD) is hypothesized to arise from imbalances between
      excitatory and inhibitory neurotransmission (E/I imbalance). Studies have
      demonstrated E/I imbalance in individuals with ASD and also corresponding rodent
      models. One neural process thought to be reliant on E/I balance is gamma-band
      activity (Gamma), with support arising from observed correlations between motor,
      as well as visual, Gamma and underlying GABA concentrations in healthy adults.
      Additionally, decreased Gamma has been observed in ASD individuals and relevant
      animal models, though the direct relationship between Gamma and GABA
      concentrations in ASD remains unexplored. This study combined
      magnetoencephalography (MEG) and edited magnetic resonance spectroscopy (MRS) in
      27 typically developing individuals (TD) and 30 individuals with ASD. Auditory
      cortex localized phase-locked Gamma was compared to resting Superior Temporal
      Gyrus relative cortical GABA concentrations for both children/adolescents and
      adults. Children/adolescents with ASD exhibited significantly decreased
      GABA+/Creatine (Cr) levels, though typical Gamma. Additionally, these
      children/adolescents lacked the typical maturation of GABA+/Cr concentrations and
      gamma-band coherence. Furthermore, children/adolescents with ASD additionally
      failed to exhibit the typical GABA+/Cr to gamma-band coherence association. This
      altered coupling during childhood/adolescence may result in Gamma decreases
      observed in the adults with ASD. Therefore, individuals with ASD exhibit improper
      local neuronal circuitry maturation during a childhood/adolescence critical
      period, when GABA is involved in configuring of such circuit functioning.
      Provocatively a novel line of treatment is suggested (with a critical time
      window); by increasing neural GABA levels in children/adolescents with ASD,
      proper local circuitry maturation may be restored resulting in typical Gamma in
      adulthood. Autism Res 2017, 10: 593-607. (c) 2016 International Society for
      Autism Research, Wiley Periodicals, Inc.

PMID- 27696741
TI  - Inflammatory Gene Expression Profile and Defective Interferon-gamma and Granzyme
      K in Natural Killer Cells From Systemic Juvenile Idiopathic Arthritis Patients.
AB  - OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) is an immunoinflammatory
      disease characterized by arthritis and systemic manifestations. The role of
      natural killer (NK) cells in the pathogenesis of systemic JIA remains unclear.
      The purpose of this study was to perform a comprehensive analysis of NK cell
      phenotype and functionality in patients with systemic JIA. METHODS:
      Transcriptional alterations specific to NK cells were investigated by RNA
      sequencing of highly purified NK cells from 6 patients with active systemic JIA
      and 6 age-matched healthy controls. Cytokines (NK cell-stimulating and others)
      were quantified in plasma samples (n = 18). NK cell phenotype and cytotoxic
      activity against tumor cells were determined (n = 10), together with their
      interferon-gamma (IFNgamma)-producing function (n = 8). RESULTS: NK cells from
      the systemic JIA patients showed an altered gene expression profile compared to
      cells from the healthy controls, with enrichment of immunoinflammatory pathways,
      increased expression of innate genes including TLR4 and S100A9, and decreased
      expression of immune-regulating genes such as IL10RA and GZMK. In the patients'
      plasma, interleukin-18 (IL-18) levels were increased, and a decreased ratio of
      IFNgamma to IL-18 was observed. NK cells from the patients exhibited specific
      alterations in the balance of inhibitory and activating receptors, with decreased
      killer cell lectin-like receptor G1 and increased NKp44 expression. Although NK
      cells from the patients showed increased granzyme B expression, consistent with
      intact cytotoxicity and degranulation against a tumor cell line, decreased
      granzyme K expression in CD56bright NK cells and defective IL-18-induced IFNgamma
      production and signaling were demonstrated. CONCLUSION: NK cells are active
      players in the inflammatory environment typical of systemic JIA. Although their
      cytotoxic function is globally intact, subtle defects in NK-related pathways,
      such as granzyme K expression and IL-18-driven IFNgamma production, may
      contribute to the immunoinflammatory dysregulation in this disease.

PMID- 27696743
TI  - Infant feeding practices in a South African birth cohort-A longitudinal study.
AB  - Childhood malnutrition is highly prevalent in low- and middle-income countries.
      The choices of complementary foods, which are important in infant nutrition, are
      poorly described in this setting. We investigated infant feeding practices in a
      South African birth cohort, the Drakenstein Child Health Study. Longitudinal
      feeding data were collected from March 2012 to March 2015. Feeding practices at
      birth, 6-10 and 14 weeks and 6, 9, and 12 months, were investigated using food
      frequency questionnaires. Anthropometry was measured at birth and 12 months. The
      quality of the diet was analyzed using the World Health Organization infant and
      young child feeding indicators. Regression models were used to explore
      associations between feeding and growth outcomes at 1 year. Exclusive
      breastfeeding for 6 months was low (13%), and 19% of infants were introduced to
      solid foods before 4 months. There was high daily consumption of processed meat
      (56%) and inappropriate foods such as fruit juice (82%), soft drinks (54%), and
      refined sugary foods (51%) at 1 year. Dietary diversity and consumption of iron
      rich foods were low at 6 months (5% and 3%, respectively) but higher by 12 months
      (75% and 78%). Longer duration of exclusive breastfeeding was associated with a
      lower height-for-age z-score at 1 year. Several dietary deficits and a rising
      trend in the consumption of inappropriate nutritionally poor foods were
      identified. These findings raise concern about poor dietary practices and the
      impact on child and long-term health.

PMID- 27696744
TI  - Reply.

PMID- 27696742
TI  - Genome-Wide Association Study of Radiographic Knee Osteoarthritis in North
      American Caucasians.
AB  - OBJECTIVE: A major barrier to genetic studies of osteoarthritis (OA) is the need
      to obtain large numbers of individuals with standardized radiographic evaluations
      for OA. To address this gap, we performed a genome-wide association study (GWAS)
      of radiographically defined tibiofemoral knee OA in 3,898 cases and 3,168
      controls from 4 well-characterized North American cohorts, and we performed
      replication analysis of previously reported OA loci. METHODS: We performed meta
      analysis using a 2-stage design. Stage 1 (discovery) consisted of a GWAS meta
      analysis of radiographic knee OA carried out in the Osteoarthritis Initiative and
      the Johnston County Osteoarthritis Project. Knee OA was defined as definite
      osteophytes and possible joint space narrowing or total joint replacement in one
      or both knees. Stage 2 (validation) was performed in the Multicenter
      Osteoarthritis Study and the Genetics of Osteoarthritis study. We genotyped lead
      meta-analysis variants (P <= 1 * 10-4 ) from stage 1 and tested the association
      between these variants and knee OA. We then combined results from all cohorts in
      a meta-analysis. RESULTS: Lead variants from stage 1, representing 49 unique
      loci, were analyzed in stage 2; none met genome-wide significance in the combined
      analysis of stage 1 and stage 2. We validated 1 locus (rs4867568 near LSP1P3)
      with nominal significance (P < 0.05), which was also our top finding in the
      combined meta-analysis (odds ratio [OR] 0.84 [95% confidence interval (95% CI)
      0.79-0.91], P = 3.02 * 10-6 ). We observed nominally significant associations (P
      < 0.05) with 3 previously reported OA loci: rs143383 in GDF5 (OR 1.12 [95% CI
      1.04-1.21], P = 2.13 * 10-3 ), rs835487 in CHST11 (OR 0.93 [95% CI 0.85-0.99], P
      = 0.03), and rs8044769 in FTO (OR 1.10 [95% CI 1.03-1.19], P = 6.13 * 10-3 ).
      CONCLUSION: These findings provide suggestive evidence of a novel knee OA locus
      and confirm previously reported associations in GDF5, CHST11, and FTO.

PMID- 27696746
TI  - Cam Deformity and Acetabular Dysplasia as Risk Factors for Hip Osteoarthritis.
AB  - OBJECTIVE: Cam deformity and acetabular dysplasia have been recognized as
      relevant risk factors for hip osteoarthritis (OA) in a few prospective studies
      with limited sample sizes. To date, however, no evidence is available from
      prospective studies regarding whether the magnitude of these associations differs
      according to sex, body mass index (BMI), and age. METHODS: Participants in the
      Rotterdam Study cohort including men and women ages 55 years or older without OA
      at baseline (n = 4,438) and a mean follow-up of 9.2 years were included in the
      study. Incident radiographic OA was defined as a Kellgren/Lawrence grade of >=2
      or a total hip replacement at follow-up. Alpha and center-edge angles were
      measured to determine the presence of cam deformity and acetabular
      dysplasia/pincer deformity, respectively. Odds ratios (ORs) were calculated to
      assess the associations between both deformities and the development of OA.
      RESULTS: Subjects with cam deformity (OR 2.11, 95% confidence interval [95% CI]
      1.55-2.87) and those with acetabular dysplasia (OR 2.19, 95% CI 1.50-3.21) had a
      2-fold increased risk of developing OA compared with subjects without deformity,
      while pincer deformity did not increase the risk of OA. Stratification analyses
      showed that the associations of cam deformity and acetabular dysplasia with OA
      were driven by younger individuals, whereas BMI did not influence the
      associations. Female sex appears to modify the risk of hip OA related to
      acetabular dysplasia. CONCLUSION: Individuals with cam deformity and those with
      acetabular dysplasia are predisposed to OA; these associations were independent
      of other well-known risk factors. Interestingly, both deformities predisposed to
      OA only in relatively young individuals. Therefore, early identification of these
      conditions is important.

PMID- 27696745
TI  - Cardiovascular parameters of chest CT scan in estimating pulmonary arterial
      pressure in patients with pulmonary hypertension.
AB  - OBJECTIVE: To develop a formula to compute mean pulmonary arterial pressure
      (MPAP) by chest computerized tomography (CT), and to verify its accuracy and
      reliability. METHODS: Eighty-five patients who had taken chest CT and right heart
      catheterization (RHC) were recruited. The pulmonary arterial systolic pressure
      (PASP), pulmonary arterial diastolic pressure (PADP), and MPAP of each subject
      were measured and recorded by RHC. The diameters of the ascending aorta (dAA),
      descending aorta (dDA) and main pulmonary artery (dMPA), Cobb angle, diameters of
      right ventricle (dRV), diameters of left ventricle (dLV) were measured by means
      of chest CT scans. Systolic blood pressure (SBP) was measured by using electronic
      sphygmomanometer. A linear regression equation was generated in 56 patients to
      estimate PAP based on chest CT values, 29 patients were used to test the accuracy
      of the formula. RESULTS: The computed equation for analyzing MPAP is: MPAP =
      9.011 + 34.195 * dMPA/dAA - 0.319 * SBP + 0.402 * Cobb angle. AUC of equation
      with three variables (dMPA/dAA, SBP, and Cobb angle) was 0.923 with 95% CI (0.863
      0.982). The mean +/- SD of predicted values and RHC values had no statistical
      difference. CONCLUSIONS: Ratio of dMAP/dAA, Cobb angle, and SBP can be reliably
      used to estimate MPAP and predict severity of PH.

PMID- 27696747
TI  - Endobronchial involvement as an extremely rare manifestation of the Waldenstrom's
      disease.
AB  - Pulmonary infiltration is an infrequent organ involvement in Waldenstrom's
      disease (WD). Diffuse infiltration, isolated parenchymatous nodules, and pleural
      effusion are the most common manifestations of WD, while endobronchial mass is
      extremely rare. We present a case report of a 66-year-old man with a long
      standing history of WD, who developed febrile neutropenia after therapy with
      rituximab, cyclophosphamide, and dexamethasone. X-ray and CT scan showed
      consolidation consistent with right-sided pneumonia. Surprisingly, bronchoscopy
      revealed an endobronchial tumor obstructing the right lower lobe (RLL) and two
      smaller granulations. Biopsies were obtained and recanalization of the RLL
      bronchus was performed. Immunohistological staining of the samples was consistent
      with lymphoplasmacytic lymphoma. Despite the change in therapy the patient died 6
      weeks later. A review of published literature revealed only two case reports of
      endobronchial involvement in WD to this day. While one of the case reports
      described a patient with diffuse submucosal infiltration of the airways, the
      other one presented a patient with bronchus-obstructing tumor similar to the case
      reported here.

PMID- 27696750
TI  - Mediating Effect of Changes in Hand Impairments on Hand Function in Patients With
      Rheumatoid Arthritis: Exploring the Mechanisms of an Effective Exercise Program.
AB  - OBJECTIVE: To determine whether the effect of the Strengthening and Stretching
      for Rheumatoid Arthritis of the Hand (SARAH) exercise program on hand function
      was mediated by changes in the proposed active ingredients: strength, dexterity,
      and/or range of motion. METHODS: The SARAH intervention included exercises
      hypothesized to improve potential mediators of grip strength, pinch strength,
      wrist flexion, wrist extension, finger flexion, finger extension, thumb
      opposition, and dexterity, which would theoretically improve self-reported hand
      function. All variables were measured at baseline and at 4 and 12 months.
      Structural equation modeling was used to assess mediation on change in hand
      function via change in potential mediators. RESULTS: Change in grip strength
      partially mediated change in hand function. Grip strength mediated 19.4% (95%
      confidence interval 0.9%, 37.8%) of the treatment effect. CONCLUSION:
      Improvements in grip strength at 4 months are likely to mediate improved hand
      function at 12 months. The role of joint mobility exercises is less clear and is
      likely influenced by the choice of measurement tools for both mobility and
      function outcomes. More robust measurements of wrist and hand mobility for
      patients with rheumatoid arthritis may be necessary to determine the relationship
      between this variable and self-reported hand function. Using a large trial data
      set, we have demonstrated that techniques used to target grip strength are key
      active ingredients of the SARAH exercise program and mediate its effect.

PMID- 27696748
TI  - PDGF is a potent initiator of bone formation in a tissue engineered model of
      pathological ossification.
AB  - Heterotopic ossification (HO) is a debilitating condition defined by the rapid
      formation of bone in soft tissues. What makes HO fascinating is first the rate at
      which bone is deposited, and second the fact that this bone is structurally and
      compositionally similar to that of a healthy adult. If the mechanisms governing
      HO are understood, they have the potential to be exploited for the development of
      potent osteoinductive therapies. With this aim, a tissue-engineered skeletal
      muscle was used model to better understand the role of inflammation on this
      debilitating phenomenon. It was shown that myoblasts could be divided into two
      distinct populations: myogenic cells and undifferentiated 'reserve' cells. Gene
      expression analysis of myogenic and osteoregulatory markers confirmed that
      'reserve' cells were primed for osteogenic differentiation but had a reduced
      capacity for myogenesis. Osteogenic differentiation was significantly enhanced in
      the presence of platelet-derived growth factor (PDGF)-BB and bone morphogenetic
      protein 2 (BMP2), and correlated with conversion to a Sca-1+ /CD73+ phenotype.
      Alizarin red staining showed that PDGF-BB promoted significantly more mineral
      deposition than BMP2. Finally, it was shown that PDGF-induced mineralization was
      blocked in the presence of the pro-inflammatory cytokines tumour necrosis factor
      alpha and interleukin 1. In conclusion, the present study identified that PDGF-BB
      is a potent osteoinductive factor in a model of tissue-engineered skeletal
      muscle, and that the osteogenic capacity of this protein was modulated in the
      presence of pro-inflammatory cytokines. These findings reveal a possible
      mechanism by which HO develops following trauma. Importantly, these findings have
      implications for the induction and control of bone formation for regenerative
      medicine. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27696749
TI  - Participation of protein kinases and phosphatases in the progesterone-induced
      acrosome reaction and calcium influx in human spermatozoa.
AB  - In human spermatozoa, protein kinases have a role in the acrosome reaction (AR)
      induced by a variety of stimuli. However, there is disagreement or a lack of
      information regarding the role of protein kinases and phosphatases in the
      progesterone (P)-induced increase in intracellular calcium concentration ([Ca2+
      ]i ). In addition, there are no studies regarding the role of Ser/Thr and Tyr
      phosphatases and there are contradictory results regarding the role of Tyr
      kinases in the P-induced acrosome reaction. Here, we performed a simultaneous
      evaluation of the involvement of protein kinases and phosphatases in the P
      induced acrosome reaction and in the P-induced calcium influx. Motile spermatozoa
      were capacitated for 18 h and different aliquots were allocated to treated or
      control groups and then evaluated for their ability to undergo the acrosome
      reaction and to increase [Ca2+ ]i in response to P. The acrosome reaction was
      evaluated using Pisum sativum agglutinin (PSA)-FITC, and [Ca2+ ]i was evaluated
      using fura 2AM. At all of the concentrations tested, PKA inhibitors significantly
      reduced the percentage of the P-induced acrosome reaction (p < 0.001). However,
      only the highest concentrations of PKA inhibitors reduced the P-induced calcium
      influx; lower concentrations of PKA inhibitors did not affect it. Similar results
      were apparent for PKC inhibitors and for tyrosine kinase inhibitors. None of the
      Ser/Thr phosphatase inhibitors affected the P-induced acrosome reaction or the P
      induced calcium influx, except for the PP2B inhibitors that significantly reduced
      the P-induced acrosome reaction without affecting calcium influx. Finally, the
      protein tyrosine phosphatase inhibitors significantly blocked the P-induced
      acrosome reaction and reduced the amplitude of the P-induced calcium transient (p
      < 0.001) as well as the amplitude of the plateau phase (p < 0.01). The data
      suggest that protein kinases and possibly PP2B have a role on the acrosome
      reaction at some point downstream of calcium entry and that Tyr phosphatases have
      a role on the acrosome reaction upstream of calcium entry.

PMID- 27696752
TI  - High-Resolution Magnetic Resonance Imaging of Scalp Arteries and Ultrasound of
      Temporal Arteries: A Winning Strategy for Diagnosing Giant Cell Arteritis?
      Comment on the Article by Rheaume et al.

PMID- 27696753
TI  - A review of social disinhibition after traumatic brain injury.
AB  - Acquired social disinhibition refers to a debilitating behavioural syndrome
      commonly reported after a severe traumatic brain injury (TBI) and is
      characterized by inappropriate social behaviour, often described as immaturity
      and insensitivity towards others. These behaviours can have enduring effects on
      the social capability of the individual and their relationships with others.
      However, research into socially disinhibited behaviour after TBI has been
      thwarted by a lack of consensus in the literature on definition and measurement.
      This review provides an overview of our current understanding of the definition,
      measurement, prevalence, associated outcomes, neuropathology, and underlying
      mechanisms of social disinhibition after TBI. In addition, suggestions are made
      for future research to further our understanding of this syndrome with the
      eventual aim of rehabilitating problematic behaviours. It is concluded that an
      improved understanding of what causes disinhibited behaviour after TBI will be
      necessary for the development of effective treatment strategies aimed at the
      rehabilitation of underlying impairments.

PMID- 27696751
TI  - In Vivo Role of Neutrophil Extracellular Traps in Antiphospholipid Antibody
      Mediated Venous Thrombosis.
AB  - OBJECTIVE: Antiphospholipid syndrome (APS) is a leading acquired cause of
      thrombotic events. Although antiphospholipid antibodies have been shown to
      promote thrombosis in mice, the role of neutrophils has not been explicitly
      studied. The aim of this study was to characterize neutrophils in the context of
      a new model of antiphospholipid antibody-mediated venous thrombosis. METHODS:
      Mice were administered fractions of IgG obtained from patients with APS. At the
      same time, blood flow through the inferior vena cava was reduced by induction of
      stenosis. Resulting thrombi were characterized for size and neutrophil content.
      Circulating factors and the vessel wall were also assessed. RESULTS: As measured
      by both thrombus weight and thrombosis frequency, mice treated with IgG from
      patients with APS (APS IgG) demonstrated exaggerated thrombosis as compared with
      control IgG-treated mice. Thrombi in mice treated with APS IgG were enriched for
      citrullinated histone H3 (a marker of neutrophil extracellular traps [NETs]). APS
      IgG-treated mice also demonstrated elevated levels of circulating cell-free DNA
      and human IgG bound to the neutrophil surface. In contrast, circulating
      neutrophil numbers and markers of vessel wall activation were not appreciably
      different between APS IgG-treated mice and control mice. Treatment with either
      DNase (which dissolves NETs) or a neutrophil-depleting antibody reduced
      thrombosis in APS IgG-treated mice to the level in control mice. CONCLUSION:
      These data support a mechanism whereby circulating neutrophils are primed by
      antiphospholipid antibodies to accelerate thrombosis. This line of investigation
      suggests new, immunomodulatory approaches for the treatment of APS.

PMID- 27696754
TI  - Reduction in Spinal Radiographic Progression in Ankylosing Spondylitis Patients
      Receiving Prolonged Treatment With Tumor Necrosis Factor Inhibitors.
AB  - OBJECTIVE: To evaluate the course of spinal radiographic progression for up to 8
      years of followup in a large cohort of ankylosing spondylitis (AS) patients
      treated with tumor necrosis factor (TNF) inhibitors. METHODS: Consecutive
      patients from the Groningen Leeuwarden AS cohort starting TNF inhibitors between
      2004 and 2012 were included. Baseline and biannual radiographs were randomized
      with radiographs of TNF-naive AS patients and scored in chronologic order
      according to modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The
      course of radiographic progression (linear or nonlinear) was investigated using
      generalized estimating equations. Primary analysis was performed in patients with
      complete data over 4, 6, and 8 years of followup. Sensitivity analysis was
      performed after single linear imputation of missing radiographic data and after
      adjusting for patient characteristics with possible influence on radiographic
      progression. RESULTS: At baseline, median mSASSS of 210 included AS patients was
      2.8 (interquartile range 0.0-12.0), mean +/- SD mSASSS 10.0 +/- 15.5. During the
      first 4 years, radiographic progression followed a linear course (estimated mean
      progression rate was 1.7 for 0-2 and 2-4 years). A deflection from a linear
      course was found in patients with complete and imputed data over 6 and 8 years.
      The estimated mean 2-year progression rate reduced from 2.3 to 0.8 in patients
      with complete 8-year data. The same pattern was found after adjustment for
      baseline mSASSS scores, presence of syndesmophytes, sex, HLA-B27 status, age,
      symptom duration, smoking duration, body mass index, disease activity, and
      nonsteroidal antiinflammatory drug use. CONCLUSION: This observational cohort
      study in AS patients receiving long-term TNF inhibitors showed a reduction in
      spinal radiographic progression after more than 4 years of followup.

PMID- 27696755
TI  - Rheumatology Informatics System for Effectiveness: A National Informatics-Enabled
      Registry for Quality Improvement.
AB  - OBJECTIVE: The Rheumatology Informatics System for Effectiveness (RISE) is a
      national electronic health record (EHR)-enabled registry. RISE passively collects
      data from EHRs of participating practices, provides advanced quality measurement
      and data analytic capacities, and fulfills national quality reporting
      requirements. Here we report the registry's architecture and initial data, and we
      demonstrate how RISE is being used to improve the quality of care. METHODS: RISE
      is a certified Centers for Medicare and Medicaid Services Qualified Clinical Data
      Registry, allowing collection of data without individual patient informed
      consent. We analyzed data between October 1, 2014 and September 30, 2015 to
      characterize initial practices and patients captured in RISE. We also analyzed
      medication use among rheumatoid arthritis (RA) patients and performance on
      several quality measures. RESULTS: Across 55 sites, 312 clinicians contributed
      data to RISE; 72% were in group practice, 21% in solo practice, and 7% were part
      of a larger health system. Sites contributed data on 239,302 individuals. Among
      the subset with RA, 34.4% of patients were taking a biologic or targeted
      synthetic disease-modifying antirheumatic drug (DMARD) at their last encounter,
      and 66.7% were receiving a nonbiologic DMARD. Examples of quality measures
      include that 55.2% had a disease activity score recorded, 53.6% a functional
      status score, and 91.0% were taking a DMARD in the last year. CONCLUSION: RISE
      provides critical infrastructure for improving the quality of care in
      rheumatology and is a unique data source to generate new knowledge. Data
      validation and mapping are ongoing and RISE is available to the research and
      clinical communities to advance rheumatology.

PMID- 27696757
TI  - A piezoelectric device for bone work in endoscopic anterior skull base surgery -
      a feasibility study in 15 patients.

PMID- 27696756
TI  - Anti-Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis
      Associated Uveitis Refractory to Anti-Tumor Necrosis Factor Therapy: A
      Multicenter Study of Twenty-Five Patients.
AB  - OBJECTIVE: To assess the efficacy of tocilizumab (TCZ) for the treatment of
      juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: We conducted a
      multicenter study of patients with JIA-associated uveitis that was refractory to
      conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF)
      agents. RESULTS: We assessed 25 patients (21 female; 47 affected eyes) with a
      mean +/- SD age of 18.5 +/- 8.3 years. Uveitis was bilateral in 22 patients.
      Cystoid macular edema was present in 9 patients. Ocular sequelae found at
      initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n =
      10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5).
      Before TCZ, patients had received corticosteroids, conventional immunosuppressive
      drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24),
      etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2),
      anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ
      intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained
      improvement in all ocular parameters. After 6 months of therapy, 79.2% of
      patients showed improvement in anterior chamber cell numbers, and 88.2% showed
      improvement after 1 year. Central macular thickness measured by optical coherence
      tomography in patients with cystoid macular edema decreased from a mean +/- SD of
      401.7 +/- 86.8 MUm to 259.1 +/- 39.5 MUm after 6 months of TCZ (P = 0.012). The
      best-corrected visual acuity increased from 0.56 +/- 0.35 to 0.64 +/- 0.32 (P <
      0.01). After a median follow-up of 12 months, visual improvement persisted, and
      complete remission of uveitis was observed in 19 of 25 patients. Significant
      reduction in the prednisone dosage was also achieved. The main adverse effects
      were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then
      autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and
      bullous impetigo in 1 patient. CONCLUSION: TCZ appears to be a useful therapy for
      severe refractory JIA-associated uveitis.

PMID- 27696759
TI  - High cholesterol dietary intake during pregnancy is associated with large for
      gestational age in a sample of low-income women of Rio de Janeiro, Brazil.
AB  - The association between the quality of maternal dietary fat intake during
      pregnancy and the infant's birthweight (BW) remains controversial. Our goal was
      to investigate the association between maternal dietary fat intake during
      pregnancy and the rate of large for gestational age (LGA) newborns. This study
      employed a cross-sectional analysis of 297 pairs of mothers/children attending a
      public maternity at Rio de Janeiro, Brazil. BW for gestational age according to
      the Intergrowth 21st was defined as follows: adequate for gestational age (AGA <=
      90th percentile) and LGA (>90th percentile). The statistical analysis was a
      Poisson regression with robust estimations of the standard errors. Maternal
      dietary fat intake variables comprised lipids (% total energy); saturated
      (mg/1000 kcal), monounsaturated (mg/1000 kcal) and polyunsaturated (mg/1000 kcal)
      fats; and cholesterol (mg/1000 kcal), all of which were obtained with a Food
      Frequency Questionnaire. The mean BW was 3338 g (SD = 446.9), and the rate of LGA
      newborns was 13.1%. The mean maternal total energy intake was 2880 kcal (SD =
      1074), cholesterol was 154.3 mg/1000 kcal (SD = 68.1) and monounsaturated fat was
      6.9 mg/1000 kcal (SD = 2). Mothers of LGA newborns reported higher cholesterol
      dietary intake (195.8 vs. 148 mg/1000 kcal; P < 0.001), pre-pregnancy body mass
      index (25.1 vs. 23.5 kg/m2 ; P = 0.026) when compared with mothers of AGA
      newborns. Women with cholesterol intake within the fourth quartile were 2.48 (95%
      confidence interval: 1.31-4.66) times more likely to have an LGA infant compared
      with those in the 1-3 quartiles. Dietary intake of cholesterol during pregnancy
      influences LGA even after adjusting for other confounders.

PMID- 27696758
TI  - Gastrointestinal follicular lymphoma: using primary site as a predictor of
      survival.
AB  - Gastrointestinal follicular lymphoma (GI-FL) is a rare extranodal variant of
      follicular lymphoma (FL) that has been increasingly reported in the literature.
      An especially indolent course is linked to the disease after a lack of observed
      patient death in past studies. However, overall survival (OS) and associated
      prognostic factors remain unclear. A large population-based database was utilized
      to identify demographic and clinicopathologic characteristics of GI-FL, along
      with survival differences among primary sites. The Surveillance, Epidemiology,
      and End Results Registry was used to identify GI-FL cases between the years of
      1973 and 2012. Kaplan-Meier curves compared OS differences and Cox proportional
      hazard models analyzed prognostic factors. Final analysis included 1109 cases.
      Small intestinal cases, which included those with single-site and multi-segment
      involvement, were most common (63.6%) followed by gastric (18.2%) and colorectal
      cases (18.2%). Small intestinal GI-FL presented more frequently with grade I
      histology, and less often with grade III histology (P < 0.001 and P < 0.001,
      respectively). Small intestinal cases had better outcomes (5-year OS = 80.9%, P <
      0.001) compared to cases involving the stomach (5-year OS = 52.7%) and colorectum
      (5-year OS = 71.5%). On multivariate analysis for predictors of mortality, small
      intestinal involvement predicted for better survival; hazard ratio (HR) 0.66 (95%
      CI: 0.51-0.85). Advanced age (>=66), grade (grade III), and stage (Ann Arbor
      Stage III/IV) predicted for mortality with HR 5.46 (95% CI: 3.80-7.84), 1.42 (95%
      CI: 1.10-1.83), 1.57 (95% CI: 1.15-2.16), respectively. GI-FL has poorer outcomes
      than previously suggested. Small intestinal involvement has a better prognosis. A
      possible biological basis for this will require further investigations in the
      future.

PMID- 27696760
TI  - Integrating family work into the treatment of young people with severe and
      complex depression: a developmentally focused model.
AB  - AIM: Although models of family intervention are clearly articulated in the child
      and early adolescent literature, there is less clarity regarding family
      intervention approaches in later adolescence and emerging adulthood. METHODS:
      This study provides the rationale and intervention framework for a
      developmentally sensitive model of time-limited family work in the outpatient
      treatment of complex youth depression (15-25 years). RESULTS: Derived from
      current practice in the Youth Mood Clinic (YMC) at Orygen Youth Health,
      Melbourne, a stepped model of family intervention is discussed. YMC aims to
      provide comprehensive orientation, assessment and education to all families. For
      some, a family-based intervention, delivered either by the treating team or
      through the integration of a specialist family worker, offers an important
      adjunct in supporting the recovery of the young person. Developmental phases and
      challenges experienced by the young person with respect to family/caregiver
      involvement are discussed in the context of two case studies. CONCLUSIONS: A
      developmentally sensitive model is presented with particular attention to the
      developmental needs and preferences of young people. Formal evaluation of this
      model is required. Evaluation perspectives should include young people,
      caregivers, the broader family system (i.e. siblings) and the treating team (i.e.
      case manager, doctor and family worker) incorporating outcome measurement. Such
      work determines how best to apply a time-limited family-based intervention
      approach in strengthening family/caregiver relationships as part of the young
      person's recovery from severe and complex depression.

PMID- 27696761
TI  - Reply.

PMID- 27696762
TI  - Effect of Disease Activity, Glucocorticoid Exposure, and Rituximab on Body
      Composition During Induction Treatment of Antineutrophil Cytoplasmic Antibody
      Associated Vasculitis.
AB  - OBJECTIVE: We investigated the relationships between glucocorticoid use, disease
      activity, and changes in body mass index (BMI) in patients with antineutrophil
      cytoplasmic antibody-associated vasculitis (AAV). METHODS: We analyzed AAV
      patients enrolled in the Rituximab in AAV trial. Glucocorticoid use, BMI, and
      disease activity were measured regularly during the trial period. We performed
      mixed-effects regressions to examine the associations of time-dependent
      cumulative average glucocorticoid use and disease activity with changes in BMI
      over time, while adjusting for potential confounders. RESULTS: The mean +/- SD
      baseline BMI of the 197 patients enrolled was 28.8 +/- 6.3 kg/m2 . Patients with
      newly diagnosed AAV tended to have a lower mean +/- SD BMI than those with
      relapsing disease (28.0 +/- 5.7 kg/m2 versus 29.6 +/- 6.8 kg/m2 ) and higher
      disease activity (mean +/- SD Birmingham Vasculitis Activity Score for Wegener's
      Granulomatosis 8.7 +/- 3.3 versus 7.4 +/- 2.7). The most significant change in
      BMI occurred during the first 6 months of the trial (mean +/- SD increase of 1.1
      +/- 2.2 kg/m2 ; P < 0.0001). Disease activity improvement, glucocorticoid
      exposure, and randomization to rituximab were each independently associated with
      an increase in BMI (P < 0.001 for all analyses). CONCLUSION: Our findings suggest
      that changes in BMI, as well as glucocorticoid exposure, are independently
      associated with improvements in disease activity in AAV. Rituximab may also have
      effects on BMI independent of its impact on disease activity.

PMID- 27696763
TI  - Longitudinal Changes in Magnetic Resonance Imaging-Based Measures of Femorotibial
      Cartilage Thickness as a Function of Alignment and Obesity: Data From the
      Osteoarthritis Initiative.
AB  - OBJECTIVE: To investigate the interaction between malalignment and body mass
      index (BMI) on cartilage thickness change in patients with knee osteoarthritis
      (OA). METHODS: Femorotibial cartilage thickness was measured from baseline to 2
      years in 558 knees with radiographic OA. Cartilage thickness was determined in
      the central weight-bearing medial femorotibial cartilage (cMFTC) and lateral
      (cLFTC) compartments. Femorotibial angle (FTA) was stratified into neutral,
      minor, and definite malalignment. BMI was stratified using World Health
      Organization classifications for normal, overweight, and obese. Multivariable
      linear regression models were used to investigate the interaction between
      alignment and BMI, adjusting for age, sex, and disease severity. RESULTS: There
      was no significant interaction for continuous measures of alignment and BMI (P =
      0.301 for cMFTC and P = 0.852 for cLFTC). Using BMI tertiles, the association
      between alignment and medial or lateral cartilage thickness loss was not
      moderated by BMI, despite a significant association of malalignment with greater
      cartilage thickness loss (P <= 0.005). Using FTA tertiles, the association
      between BMI and medial cartilage thickness loss was approximately 3 times greater
      in knees with definite malalignment (P = 0.149) and approximately 5 times greater
      in knees with minor malalignment (P = 0.006). Specifically, knees with minor
      varus significantly modified this relationship (P = 0.021). CONCLUSION:
      Malalignment was significantly associated with cartilage thickness loss per
      degree increase in malalignment, but was not moderated by BMI. BMI was
      significantly associated with greater rates of medial cartilage thickness loss
      per unit increase in BMI but only in knees with minor varus malalignment. These
      findings have implications for better understanding patient subgroups and
      intervention strategies targeting risk factors for knee OA.

PMID- 27696764
TI  - Effects of leukotriene D4 and histamine nasal challenge on airway responsiveness
      and inflammation in persistent allergic rhinitis patients.
AB  - BACKGROUND: Both histamine and leukotrienes are implicated in the pathogenesis of
      allergic rhinitis (AR), although the pattern and severity of the nasal response
      to these two potent inflammatory mediators may differ, which has not been
      adequately studied in patients with persistent AR. OBJECTIVE: We sought to
      compare the differential effects of nasal challenge with leukotriene D4 (LTD4 )
      and histamine on the airway response and inflammation in patients with AR.
      METHODS: An open-label, crossover study was performed in 25 persistent AR
      patients (AR group) and 16 healthy subjects (control group). Participants
      randomly underwent histamine and LTD4 nasal provocation within a two-week
      interval. Nasal symptoms according to a visual analogue scale (VAS), fractional
      exhaled nitric oxide (FENO), nasal lavage, induced sputum, and spirometry were
      evaluated before and after nasal challenge. RESULTS: Nasal airway resistance
      (NAR) increased significantly after both LTD4 and histamine nasal challenge in AR
      patients (P < .05). The potency of LTD4 was 142-fold higher than that of
      histamine in increasing NAR (P < .001). The nasal symptom score induced by
      histamine challenge was significantly higher than that triggered by LTD4 (3.42 +/
      0.83 vs. 1.16 +/- 0.94, P < .05) in the AR group. LTD4 and histamine nasal
      challenge led to a significant increase in neutrophils in the nasal lavage and
      induced sputum (P < .05) in AR patients. There were no significant differences in
      the changes of eosinophils before and after LTD4 and histamine nasal challenges
      in nasal lavage and induced sputum. No significant changes in NAR, the induced
      symptom score, or inflammatory cells in the nasal lavage and sputum were found in
      the control group. CONCLUSIONS: LTD4 and histamine nasal challenge caused
      different patterns and severities of nasal symptoms, which correlated with
      symptoms (TSS) that affect patient's daily life. LTD4 was far more potent than
      histamine at increasing the NAR, while histamine nasal challenge induced more
      sneezing and nasal discharge. These results may guide the prescription of anti
      histamine or anti-leukotriene agents for treating different AR phenotypes.

PMID- 27696765
TI  - Lung function, respiratory symptoms and venous thromboembolism risk: the
      Atherosclerosis Risk in Communities Study.
AB  - : Essentials The association of lung function with venous thromboembolism (VTE)
      is unclear. Chronic obstructive pulmonary disease (COPD) patterns were associated
      with a higher risk of VTE. Symptoms were also associated with a higher risk of
      VTE, but a restrictive pattern was not. COPD may increase the risk of VTE and
      respiratory symptoms may be a novel risk marker for VTE. SUMMARY: Background The
      evidence for the association between chronic obstructive pulmonary disease (COPD)
      and venous thromboembolism (VTE) is limited. There is no study investigating the
      association between restrictive lung disease (RLD) and respiratory symptoms with
      VTE. Objectives To investigate prospectively the association of lung function and
      respiratory symptoms with VTE. Patients/Methods In 1987-1989, we assessed lung
      function by using spirometry, and obtained information on respiratory symptoms
      (cough, phlegm, and dyspnea) in 14 654 participants aged 45-64 years, without a
      history of VTE or anticoagulant use, and followed them through 2011. Participants
      were classified into four mutually exclusive groups: 'COPD' (forced expiratory
      volume in 1 s [FEV1 ]/forced vital capacity [FVC] below the lower limit of normal
      [LLN]), 'RLD' (FEV1 /FVC >= LLN and FVC < LLN), 'respiratory symptoms with normal
      spirometic results' (without RLD or COPD), and 'normal' (without respiratory
      symptoms, RLD, or COPD). Results We documented 639 VTEs (238 unprovoked and 401
      provoked VTEs). After adjustment for VTE risk factors, VTE risk was increased for
      individuals with either respiratory symptoms with normal spirometric results
      (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.12-1.73) or COPD (HR
      1.33, 95% CI 1.07-1.67) but not for those with RLD (HR 1.15, 95% CI 0.82-1.60).
      These elevated risks of VTE were derived from both unprovoked and provoked VTE.
      Moreover, FEV1 and FEV1 /FVC showed dose-response relationships with VTE. COPD
      was more strongly associated with pulmonary embolism than with deep vein
      thrombosis. Conclusions Obstructive spirometric patterns were associated with an
      increased risk of VTE, suggesting that COPD may increase the risk of VTE.
      Respiratory symptoms may represent a novel risk marker for VTE.

PMID- 27696766
TI  - Utilization of Care Outside the Veterans Affairs Health Care System by US
      Veterans With Rheumatoid Arthritis.
AB  - OBJECTIVE: Many veterans enrolled in Veterans Affairs (VA) health care systems
      also receive care through other health care systems. Both VA and non-VA health
      care use must therefore be considered when conducting research in this
      population. This study characterized dual-care utilization in veterans with
      rheumatoid arthritis (RA) and explored associations with RA disease activity.
      METHODS: Through a questionnaire mailed to RA patients at 3 VA sites, veterans
      reported medical services by non-VA primary care and subspecialty providers,
      comorbidities, non-VA medications, and hospitalizations. Disease Activity Score
      in 28 joints (DAS28) and Multidimensional Health Assessment Questionnaire (MD
      HAQ) scores were recorded during VA clinic visits, and respondent groups were
      compared. RESULTS: Of the 510 participants surveyed, 318 (62%) responded.
      Respondents were older (ages 69 versus 66 years; P = 0.006), more likely
      nonsmokers (80% versus 67%; P = 0.001), and had lower disease activity (DAS28 3.3
      versus 3.8; P < 0.001, MD-HAQ 0.8 versus 0.9; P = 0.01) than nonrespondents (n =
      192 [38%]). The respondents with a non-VA provider (n = 130 [41%]) were older (71
      versus 68 years; P = 0.001) and had more education (14 versus 13 years; P =
      0.021) than nondual-care users. Only 6% of respondents reported having a non-VA
      rheumatologist, with 2% receiving a non-VA prescribed biologic agent or disease
      modifying antirheumatic drug. CONCLUSION: In this study, VA beneficiaries with RA
      had lower dual-care utilization than previously reported for the general VA
      population, with few patients receiving dual rheumatology care or non-VA RA
      medications. This survey suggests that most US veterans with RA who access VA
      care use the VA as their primary source of arthritis care.

PMID- 27696767
TI  - Clinical Significance of Medial Versus Lateral Compartment Patellofemoral
      Osteoarthritis: Cross-Sectional Analyses in an Adult Population With Knee Pain.
AB  - OBJECTIVE: To determine the comparative prevalence, associations with selected
      patient characteristics, and clinical outcomes of medial and lateral compartment
      patellofemoral (PF) joint osteoarthritis (OA). METHODS: Information was collected
      by questionnaires, clinical assessment, and radiographs from 745 eligible
      community-dwelling symptomatic adults age >=50 years. PF joint space narrowing
      (JSN) and osteophytes were scored from skyline radiographs using the
      Osteoarthritis Research Society International atlas. Multilevel models were used
      to assess associations of compartmental PF joint OA with age, sex, body mass
      index (BMI) and varus-valgus malalignment, while median regression was used to
      examine associations with clinical outcomes (current pain intensity on a numeric
      rating scale [0-10] and the function subscale of the Western Ontario and McMaster
      Universities Osteoarthritis Index [0-68]). RESULTS: Isolated lateral PF joint OA
      was more common than isolated medial PF joint OA, particularly at higher severity
      thresholds. Irrespective of severity threshold, age (>=2 odds ratio [OR] 1.19
      [95% confidence interval (95% CI) 1.12, 1.26]), BMI (>=2 OR 1.15 [95% CI 1.07,
      1.24]), and valgus malalignment (>=2 OR 2.58 [95% CI 1.09, 6.07]) were associated
      with increased odds of isolated lateral JSN, but isolated medial JSN was only
      associated with age (>=2 OR 1.20 [95% CI 1.14, 1.27]). The pattern of association
      was less clear for PF joint osteophytes. Isolated lateral PF joint OA, defined by
      JSN or osteophytes, was associated with higher pain scores than isolated medial
      PF joint OA, but these differences were modest and were not significant. A
      similar pattern of association was seen for functional limitation but only when
      PF joint OA was defined by JSN. CONCLUSION: Isolated lateral PF joint OA is more
      common than isolated medial PF joint OA, and it is more consistently associated
      with established OA risk factors. It is also associated with higher, but
      clinically nonsignificant, pain and function scores than isolated medial PF joint
      OA, particularly when PF joint OA is defined using JSN.

PMID- 27696768
TI  - CD8+ T Cells Contribute to the Development of Coronary Arteritis in the
      Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease.
AB  - OBJECTIVE: Kawasaki disease (KD) is the leading cause of acquired heart disease
      among children in developed countries. Coronary lesions in KD in humans are
      characterized by an increased presence of infiltrating CD3+ T cells; however, the
      specific contributions of the different T cell subpopulations in coronary
      arteritis development remain unknown. Therefore, we sought to investigate the
      function of CD4+ and CD8+ T cells, Treg cells, and natural killer (NK) T cells in
      the pathogenesis of KD. METHODS: We addressed the function of T cell subsets in
      KD development by using a well-established murine model of Lactobacillus casei
      cell wall extract (LCWE)-induced KD vasculitis. We determined which T cell
      subsets were required for development of KD vasculitis by using several knockout
      murine strains and depleting monoclonal antibodies. RESULTS: LCWE-injected mice
      developed coronary lesions characterized by the presence of inflammatory cell
      infiltrates. Frequently, this chronic inflammation resulted in complete occlusion
      of the coronary arteries due to luminal myofibroblast proliferation (LMP) as well
      as the development of coronary arteritis and aortitis. We found that CD8+ T
      cells, but not CD4+ T cells, NK T cells, or Treg cells, were required for
      development of KD vasculitis. CONCLUSION: The LCWE-induced murine model of KD
      vasculitis mimics many histologic features of the disease in humans, such as the
      presence of CD8+ T cells and LMP in coronary artery lesions as well as epicardial
      coronary arteritis. Moreover, CD8+ T cells functionally contribute to the
      development of KD vasculitis in this murine model. Therapeutic strategies
      targeting infiltrating CD8+ T cells might be useful in the management of KD in
      humans.

PMID- 27696769
TI  - Synthesis and preliminary evaluation of a 18 F-labeled ethisterone derivative [18
      F]EAEF for progesterone receptor targeting.
AB  - To develop a novel progesterone receptor-targeting probe for positron emission
      tomography imaging, an ethisterone derivative [18 F]EAEF was designed and
      prepared in high decay-corrected radiochemical yield (30-35%) with good
      radiochemical purity (>98%). [18 F]EAEF is a lipophilic tracer (logP = 0.53 +/-
      0.06) with very good stability in saline and serum. In the biodistribution study,
      high radioactivity accumulation of [18 F]EAEF were found in uterus (5.73 +/-
      1.83% ID/g) and ovary (4.05 +/- 0.73% ID/g) at 2 hr postinjection (p.i.), which
      have high progesterone receptor expression after treated with estradiol, while
      the muscle background has very low uptake (0.50 +/- 0.17% ID/g). For positron
      emission tomography imaging, [18 F]EAEF showed high uptake in progesterone
      receptor-positive MCF-7 tumor (3.15 +/- 0.07% ID/g at 2 hr p.i.) with good tumor
      to muscle ratio (2.90), and obvious lower tumor uptakes were observed in MCF-7
      with EAEF blocking (1.84 +/- 0.05% ID/g at 2 hr p.i.) or in progesterone receptor
      negative MDA-MB-231 tumor (1.80 +/- 0.03% ID/g at 2 hr p.i.). Based on the good
      stability and specificity of [18 F]EAEF, it may be a good candidate for imaging
      progesterone receptor and worth further investigation.

PMID- 27696771
TI  - Metformin Represses Interferonopathy Through Suppression of Melanoma
      Differentiation-Associated Protein 5 and Mitochondrial Antiviral Signaling
      Protein Activation: Comment on the Article by Wang et al.

PMID- 27696772
TI  - Circulating CD8+CD28null T Cytotoxic Cells in Polymyositis-A Possible Biomarker?
      Comment on the Article by Pandya et al.

PMID- 27696770
TI  - Allergy and asthma medication use in home-dwelling U.S. older adults.
AB  - BACKGROUND: Little is known about the use of allergy and asthma medications in
      older adults. This study aimed to assess the prevalence of use of these
      medications in older adults and evaluate predictors of their use. METHODS: Cross
      sectional study using data from the National Social Life, Health, and Aging
      Project (NSHAP), a nationally representative sample of community-dwelling, U.S.
      adults 57 to 85 years (n = 2976) collected in 2005-2006. We determined prevalence
      of medication use and used logistic regression to evaluate sociodemographic and
      health factors associated with their use. RESULTS: Overall prevalence of allergy
      medication usage was 8.4% (most commonly antihistamines), and prevalence of
      asthma medication usage was 8.0% (most commonly bronchodilators). Allergy
      medication use was significantly associated with history of asthma (odds ratio
      [OR] 2.37; 95% confidence interval [CI], 1.52 to 3.69), chronic obstructive
      pulmonary disease (COPD) (OR 2.35; 95% CI, 1.58 to 3.51), or nasal surgery (OR
      1.97; 95% CI, 1.00 to 3.86). Older age was associated with decreased allergy
      medication use (per decade, OR 0.80; 95% CI, 0.66 to 0.98). Although increased
      education was associated with increased overall allergy medication use, it was
      associated with decreased use of allergy medications generally contraindicated in
      the elderly. In contrast, the only significant predictors of asthma medication
      use were history of asthma (OR 19.66; 95% CI, 3.18 to 121.70) or COPD (OR 4.25;
      95% CI, 0.88 to 20.44). CONCLUSION: Allergy and asthma medication use is
      prevalent among older adults and driven mostly by history of asthma or COPD.
      Additional sociodemographic factors predict allergy (but not asthma) medication
      use. Further studies are needed to evaluate efficacy of these drugs in the
      elderly.

PMID- 27696774
TI  - Detection of erythropoietin misuse by the Athlete Biological Passport combined
      with reticulocyte percentage.
AB  - The sensitivity of the adaptive model of the Athlete Biological Passport (ABP)
      and reticulocyte percentage (ret%) in detection of recombinant human
      erythropoietin (rHuEPO) misuse was evaluated using both a long-term normal dose
      and a brief high dose treatment regime. Sixteen subjects received either 65 IU
      rHuEPO * kg-1 every second day for two weeks (normal-dose), 390 IU rHuEPO * kg-1
      on three consecutive days (high-dose), or frequent placebo treatment for 13 days
      in a randomized, placebo-controlled, double-blind crossover design. Blood
      variables were measured 4, 11, and 25 days following treatment initiation. The
      ABP based on haemoglobin concentration ([Hb]) and OFF-hr score ([Hb] - 60 *
      ?ret%) yielded atypical profiles following both normal-dose and high-dose
      treatment (0 %, 31 %, 13 % vs. 21 %, 33 %, 20 % at days 4, 11, and 25 after
      normal and high dose, respectively). Including ret% as a stand-alone marker for
      atypical blood profiles increased (P < 0.05) the sensitivity of the adaptive
      model at day 11 to 63 % and 67 % for normal-dose and high-dose rHuEPO
      administration, respectively. In conclusion, ~30 % of subjects injecting a normal
      dose rHuEPO for two weeks or a high-dose rHuEPO for three days will present an
      atypical ABP profile. Including ret% as a stand-alone parameter improves the
      sensitivity two-fold. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 27696773
TI  - Effectiveness of Ultrasound-Guided Compared to Blind Steroid Injections in the
      Treatment of Carpal Tunnel Syndrome.
AB  - OBJECTIVE: To compare the effectiveness of ultrasound-guided injections to blind
      injections in the treatment of carpal tunnel syndrome (CTS) in a large community
      based cohort. METHODS: This study evaluated residents of Olmsted County,
      Minnesota, treated with a corticosteroid injection for CTS between 2001 and 2010.
      The proportion of patients receiving retreatment and the duration of retreatment
      free survival between blind and ultrasound-guided injections were compared.
      Propensity score matching was used to control for confounding by indication.
      RESULTS: In the matched data set consisting of 234 (of 600) hands treated with a
      blind injection and 87 (of 89) ultrasound-guided injection cases, ultrasound
      guidance was associated with a reduced hazard of retreatment (hazard ratio 0.59
      [95% confidence interval (95% CI) 0.37-0.93]). In addition, ultrasound guidance
      was associated with 55% reduced odds of retreatment within 1 year compared to
      blind injections (adjusted odds ratio 0.45 [95% CI 0.24-0.83]). CONCLUSION: This
      study indicates that ultrasound-guided injections are more effective in
      comparison to blind injections in the treatment of CTS.

PMID- 27696776
TI  - 5alpha-Dihydrotestosterone negatively regulates cell proliferation of the
      periurethral ventral mesenchyme during urethral tube formation in the murine male
      genital tubercle.
AB  - Androgen is an essential factor involved in masculinization of external
      genitalia. Failure of the exposure to 5alpha-dihydrotestosterone (DHT) causes a
      hypoplastic penile size and urethral abnormality. The main pathology of
      hypospadias is defective urethral closure on the ventral side of the penis.
      Hormone-dependent genes are suggested as the causative factors. However, the
      detailed mechanisms of DHT functions on urethral tube formation remain unknown.
      Androgen is both a positive and negative regulator of cell proliferation. The
      roles of locally converted DHT in cell proliferation at the periurethral
      mesenchyme have not been elucidated. We revealed the expression pattern of 5alpha
      reductase type 2 mRNA (Srd5a2) and local DHT distribution by direct measurement
      in this study. We also analyzed periurethral mesenchymal cell proliferation
      status using systematic three-dimensional (3D) reconstruction analyses. A
      prominent Srd5a2 expression and localized DHT distribution on the ventral side of
      the genital tubercle were detected. Cell proliferation was reduced in this
      mesenchymal region during urethral formation. The current results suggest the
      presence of the possible negative regulation of cell proliferation by DHT.
      Moreover, cell proliferation related to urethral tube formation was revealed to
      be DHT dose dependent. These data are expected to contribute to the understanding
      of the mode of regulation of cell proliferation related to urethral tube
      formation by DHT. These findings may also offer insight into the understanding of
      human hypospadias and related hormone-dependent factors.

PMID- 27696775
TI  - Laccase: a multi-purpose biocatalyst at the forefront of biotechnology.
AB  - Laccases are multicopper containing enzymes capable of performing one electron
      oxidation of a broad range of substrates. Using molecular oxygen as the final
      electron acceptor, they release only water as a by-product, and as such, laccases
      are eco-friendly, versatile biocatalysts that have generated an enormous
      biotechnological interest. Indeed, this group of enzymes has been used in
      different industrial fields for very diverse purposes, from food additive and
      beverage processing to biomedical diagnosis, and as cross-linking agents for
      furniture construction or in the production of biofuels. Laccases have also been
      studied intensely in nanobiotechnology for the development of implantable
      biosensors and biofuel cells. Moreover, their capacity to transform complex
      xenobiotics makes them useful biocatalysts in enzymatic bioremediation. This
      review summarizes the most significant recent advances in the use of laccases and
      their future perspectives in biotechnology.

PMID- 27696777
TI  - Association of Anti-Citrullinated Peptide Antibodies With Coronary Artery
      Calcification in Rheumatoid Arthritis.
AB  - OBJECTIVE: Citrullinated proteins have been found within atherosclerotic plaque.
      However, studies evaluating the association between anti-citrullinated protein
      antibodies (ACPAs) and imaging measures of atherosclerosis in patients with
      rheumatoid arthritis (RA) have been limited to seroreactive citrullinated
      fibrinogen or citrullinated vimentin and have rendered contradictory results.
      Therefore, our objective was to evaluate this association using an extended panel
      of ACPAs in a larger sample of RA patients without clinical cardiovascular
      disease (CVD). METHODS: ACPAs were identified using a custom Bio-Plex bead assay
      in 270 patients from 2 independent RA cohorts without clinical CVD, with the
      first one consisting of 195 patients and the other of 75 patients. Coronary
      artery calcium (CAC) was assessed by computed tomography as a measure of coronary
      artery disease. RESULTS: High levels of anti-citrullinated histone H2B antibodies
      were strongly associated with higher CAC scores, compared with lower antibody
      levels (P = 0.001); this remained significant after adjustment for traditional CV
      and RA-specific risk factors (P = 0.03). No association between levels of ACPAs
      and CAC progression at 3 years was seen (P = 0.09); however, the number of
      progressors was small (n = 92). CONCLUSION: Higher levels of ACPAs targeting Cit
      histone H2B were associated with higher CAC scores when compared to lower
      antibody levels, suggesting a potential role for histone citrullination
      seroreactivity in atherosclerosis.

PMID- 27696780
TI  - Reply.

PMID- 27696778
TI  - Little Evidence for Usefulness of Biomarkers for Predicting Successful Dose
      Reduction or Discontinuation of a Biologic Agent in Rheumatoid Arthritis: A
      Systematic Review.
AB  - OBJECTIVE: To systematically review studies addressing prediction of successful
      dose reduction or discontinuation of a biologic agent in rheumatoid arthritis
      (RA). METHODS: PubMed, Embase, and Cochrane Library databases were searched for
      studies that examined the predictive value of biomarkers for successful dose
      reduction or discontinuation of a biologic agent in RA. Two reviewers
      independently selected studies, and extracted data and assessed the risk of bias.
      A biomarker was classified as a "potential predictor" if the univariate
      association was either strong (odds ratio or hazard ratio >2.0 or <0.5) or
      statistically significant. For biomarkers that were studied multiple times,
      qualitative best-evidence synthesis was performed separately for the prediction
      of successful dose reduction and discontinuation. Biomarkers that were defined in
      >=75% of the studies as potential predictors were regarded as "predictor" for the
      purposes of our study. RESULTS: Of 3,029 nonduplicate articles initially
      searched, 16 articles regarding 15 cohorts were included in the present study.
      Overall, 17 biomarkers were studied multiple times for the prediction of
      successful dose reduction, and 33 for the prediction of successful
      discontinuation of a biologic agent. Three predictors were identified: higher
      adalimumab trough level for successful dose reduction and lower Sharp/van der
      Heijde erosion score and shorter symptom duration at the start of a biologic
      agent for successful discontinuation. CONCLUSION: The predictive value of a wide
      variety of biomarkers for successful dose reduction or discontinuation of
      biologic treatment in RA has been investigated. We identified only 3 biomarkers
      as predictors, in just 2 studies. The strength of the evidence is limited by the
      low quality of the included studies and the likelihood of reporting bias and
      multiple testing.

PMID- 27696779
TI  - Standards of Comparison and Discordance in Rheumatoid Arthritis Global
      Assessments Between Patients and Clinicians.
AB  - OBJECTIVE: Patient-physician discordance in health status ratings may arise
      because patients use temporal comparisons (comparing their current status with
      their previous status), while clinicians use social comparisons (comparing this
      patient's status to that of other patients, or to the full range of disease
      severity possible) to guide their assessments. We compared discordance between
      patients with rheumatoid arthritis (RA) and clinicians, using either the
      conventional patient global assessment (PGA) or a rating scale with 5 anchors
      describing different health states. We hypothesized that discordance would be
      smaller with the rating scale because clinicians likely used similar social
      comparisons when making global assessments. METHODS: We prospectively studied 206
      patients with active RA and assessed the PGA (range 0-100), rating scale (range 0
      100), and evaluator global assessment (EGA; range 0-100) on each of 2 visits
      (total visits = 401). We compared the PGA/EGA discordance and the rating
      scale/EGA discordance at each visit. RESULTS: The mean +/- SD PGA/EGA discordance
      was 8.5 +/- 22.4, and the mean +/- SD rating scale/EGA discordance was 2.3 +/-
      24.0. The intraclass correlation, measuring agreement, was higher between the
      rating scale and EGA than between the PGA and EGA (0.39 versus 0.31). Agreement
      was larger at low levels of RA activity on both pairs of measures. CONCLUSION:
      Discordance between patients' global assessments and evaluators' global
      assessments was smaller when patients used a social standard of comparison than
      when they marked the PGA, suggesting that differences in standards of comparison
      contribute to patient-clinician discordance when the PGA is used.

PMID- 27696781
TI  - Supercritical fluid chromatography for lipid analysis in foodstuffs.
AB  - The task of lipid analysis has always challenged separation scientists, and new
      techniques in chromatography were often developed for the separation of lipids;
      however, no single technique or methodology is yet capable of affording a
      comprehensive screening of all lipid species and classes. This review acquaints
      the role of supercritical fluid chromatography within the field of lipid
      analysis, from the early developed capillary separations based on pure CO2 , to
      the most recent techniques employing packed columns under subcritical conditions,
      including the niche multidimensional techniques using supercritical fluids in at
      least one of the separation dimensions. A short history of supercritical fluid
      chromatography will be introduced first, from its early popularity in the late
      1980s, to the sudden fall and oblivion until the last decade, experiencing a
      regain of interest within the chromatographic community. Afterwards, the subject
      of lipid nomenclature and classification will be briefly dealt with, before
      discussing the main applications of supercritical fluid chromatography for food
      analysis, according to the specific class of lipids.

PMID- 27696783
TI  - Editorial: Caught in the Act: Dissecting Natural Killer Cell Function in Systemic
      Juvenile Idiopathic Arthritis.

PMID- 27696782
TI  - Human Endogenous Retroviral Genetic Element With Immunosuppressive Activity in
      Both Human Autoimmune Diseases and Experimental Arthritis.
AB  - OBJECTIVE: Human endogenous retroviruses (HERVs) are remnants of past retroviral
      infections in the human genome and have been implicated in different aspects of
      human biology. The aim of this study was to identify HERVs that are associated
      with the pathogenesis of rheumatic diseases such as systemic lupus erythematosus
      (SLE). METHODS: The study subjects included 45 female patients with SLE and 50
      healthy controls matched for geographic area, age, and sex. Real-time reverse
      transcription-polymerase chain reaction analysis was used to examine the
      transcription levels of 11 genes with coding capacity for complete envelope (Env)
      protein in these individuals. In this way, 1 HERV locus was identified as a
      potential modulator of autoimmunity. The env gene encoded by this HERV locus was
      cloned and examined for the ability to express a functional protein with
      immunosuppressive potential. RESULTS: Expression of the env59 gene was negatively
      correlated with pathogenetic factors of human autoimmune rheumatic diseases,
      including such factors as the levels of interleukin-6 (IL-6) and Toll-like
      receptor 7. This gene was capable of encoding a fully functional Env glycoprotein
      that was found to contain a domain, the immunosuppressive (ISU) domain, that,
      when evaluated ex vivo in patients with SLE and those with rheumatoid arthritis
      as well as in animal models, showed strong antiinflammatory activity, including
      the ability to lower IL-6 levels. CONCLUSION: The env59 gene has been adapted by
      the immune system as a control mechanism in autoimmunity. The peptides derived
      from the ISU domain contained in the Env59 protein may be useful as potentially
      new biologic treatments in rheumatic diseases such as SLE.

PMID- 27696784
TI  - Relationship Between Neuromyelitis Optica Spectrum Disorder and Sjogren's
      Syndrome: Central Nervous System Extraglandular Disease or Unrelated, Co
      Occurring Autoimmunity?
AB  - OBJECTIVE: Sjogren's syndrome (SS) patients may be affected by the neuromyelitis
      optica spectrum disorder (NMOSD), a severe demyelinating syndrome associated with
      anti-aquaporin 4 antibodies (anti-AQP-4 antibodies). The relationship between SS
      and NMOSD has been a sustained focus of investigation. Among SS patients, anti
      AQP-4 antibodies have been detected exclusively in those with NMOSD. It has
      therefore been speculated that NMOSD is not a neurologic complication of SS.
      However, such studies evaluated small numbers of SS patients, often mixed with
      other inflammatory disorders. METHODS: We compared frequencies of anti-AQP-4 and
      SS-associated antibodies in 109 SS patients, including 11 with NMOSD, 8 with non
      NMOSD demyelinating syndromes, and 90 without demyelinating syndromes. RESULTS:
      When assessed using a fluorescence-activated cell sorting (FACS) assay, anti-AQP
      4 antibodies were seen exclusively in those SS patients with NMOSD (72.7%), but
      not in SS patients without NMOSD (P < 0.01). In contrast, anti-Ro 52, anti-Ro 60,
      and other autoantibodies were not more prevalent in SS patients with NMOSD versus
      those without. Anti-AQP-4 antibodies were detected more frequently among NMOSD
      patients by FACS assay than with a commercial immunohistochemical assay (72.7%
      versus 54.5%), despite assessment after a more prolonged period of
      immunosuppressive therapy (median 38 months versus 5 months; P < 0.01).
      CONCLUSION: The syndrome-specificity of anti-AQP-4 antibodies, along with an
      otherwise similar antibody profile in SS NMOSD patients, indicates that NMOSD is
      not a direct central nervous system manifestation of SS. Anti-AQP-4 antibodies
      can persist and be refractory to prolonged immunosuppressive therapy.

PMID- 27696785
TI  - Fifty-one full-length major histocompatibility complex class II alleles in the
      olive baboon (Papio anubis).
AB  - Here we report 51 novel major histocompatibility complex (MHC) class II alleles
      in a group of related olive baboons.

PMID- 27696786
TI  - Secukinumab for Long-Term Treatment of Psoriatic Arthritis: A Two-Year Followup
      From a Phase III, Randomized, Double-Blind Placebo-Controlled Study.
AB  - OBJECTIVE: To assess the 2-year efficacy and safety of the interleukin-17A
      inhibitor, secukinumab, in active psoriatic arthritis (PsA). METHODS: In the
      FUTURE-1 study, 606 patients with active PsA were randomized to secukinumab 10
      mg/kg intravenously at baseline, and at weeks 2 and 4, followed by 150 mg or 75
      mg subcutaneously (SC) every 4 weeks from week 8, or matching placebo. Patients
      receiving placebo were re-randomized to secukinumab 150 mg or 75 mg SC from week
      16 or week 24, depending upon clinical response. Treatment continued to week 104.
      Exploratory analysis of all primary and secondary end points, on an intent-to
      treat basis, continued to week 104. RESULTS: A total of 476 patients (78.5%)
      completed 104 weeks of treatment. Secukinumab showed sustained efficacy across
      multiple domains of PsA through week 104, including signs and symptoms, disease
      activity, quality of life, physical function, skin symptoms, dactylitis, and
      enthesitis. American College of Rheumatology criteria for 20% improvement
      response rates were 66.8% with secukinumab 150 mg and 58.6% with secukinumab 75
      mg at week 104; Psoriasis Area and Severity Index criteria for 75% improvement
      response rates were 74.6% and 63.0%, respectively (multiple imputed data). At
      week 104, 84.3% of patients in the secukinumab 150 mg group and 83.8% in the
      secukinumab 75 mg group showed no radiographic disease progression (observed
      data). No new or unexpected safety signals were reported during 2 years of
      treatment. Immunogenicity to secukinumab was low. CONCLUSION: Secukinumab
      provided sustained improvements in PsA at 2 years, with very little radiographic
      progression. Treatment was well tolerated over the long term.

PMID- 27696787
TI  - A PEGylated bovine hemoglobin as a potent hemoglobin-based oxygen carrier.
AB  - Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been used as blood substitutes
      in surgery medicine and oxygen therapeutics for ischemic stroke. As a potent
      HBOC, the PEGylated Hb has received much attention for its oxygen delivery and
      plasma expanding ability. Two PEGylated Hbs, Euro-Hb, and MP4 have been developed
      for clinical trials, using human adult hemoglobin (HbA) as the original
      substrate. However, HbA was obtained from outdated human blood and its quantity
      available from this source may not be sufficient for mass production of PEGylated
      HbA. In contrast, bovine Hb (bHb) has no quantity constraints for its ample
      resource. Thus, bHb is of potential to function as an alternative substrate to
      obtain a PEGylated bHb (bHb-PEG). bHb-PEG was prepared under the same reaction
      condition as HbA-PEG, using maleimide chemistry. The structural, functional,
      solution and physiological properties of bHb-PEG were determined and compared
      with those of HbA-PEG. bHb-PEG showed higher hydrodynamic volume, colloidal
      osmotic pressure, viscosity and P50 than HbA-PEG. The high P50 of bHb can
      partially compensate the PEGylation-induced perturbation in the R to T state
      transition of HbA. bHb-PEG was non-vasoactive and could efficiently recover the
      mean arterial pressure of mice suffering from hemorrhagic shock. Thus, bHb-PEG is
      expected to function as a potent HBOC for its high oxygen delivery and strong
      plasma expanding ability. (c) 2016 American Institute of Chemical Engineers
      Biotechnol. Prog., 33:252-260, 2017.

PMID- 27696788
TI  - Coronary Artery Calcification and Rheumatoid Arthritis: Lack of Relationship to
      Risk Alleles for Coronary Artery Disease in the General Population.
AB  - OBJECTIVE: Coronary artery disease (CAD) in the general population is
      characterized by an increased frequency of particular susceptibility single
      nucleotide polymorphisms (SNPs). Because the frequency of CAD is increased among
      patients with rheumatoid arthritis (RA), we sought to determine whether the
      frequency of these SNPs is increased in RA patients with CAD, hypothesizing that
      RA could enhance CAD risk by acting through established genetic pathways
      predisposing to CAD. METHODS: Coronary artery calcification (CAC) as detected by
      computed tomography was used as a measure of CAD in 561 patients with RA. One
      hundred SNPs associated with CAD in the general population were genotyped or
      imputed, and their relationship to CAC was established through multiple
      regression analysis for individual SNPs and a genetic risk score representing
      their cumulative effect. RESULTS: Ninety-one CAD-related SNPs were genotyped
      successfully; of these, 81 exhibited no association with CAC (Agatston units) or
      different CAC categorizations, either individually or collectively, in the
      genetic risk score. Only rs579459 (ABO) and rs17676451 (HAL) had a consistent
      positive association between genotype and CAC, with a significant increase in the
      frequency of the effect allele in both homozygous and heterozygous genotype
      distributions. Five were variably negatively associated. Furthermore, a positive
      association between the Disease Activity Score in 28 joints and CAC was observed,
      and after adjustment for traditional cardiovascular risk factors, it was not
      modified by correcting for the CAD-related SNP genetic risk score. CONCLUSION:
      The increased risk of CAC in patients with RA does not appear to operate
      primarily through established genetically regulated atherogenic mechanisms that
      are preponderant in the general population.

PMID- 27696791
TI  - Defining Low Disease Activity in Systemic Lupus Erythematosus.
AB  - OBJECTIVE: To define and identify a group of systemic lupus erythematosus
      patients with low disease activity (LDA) and to examine whether LDA is similar to
      patients in remission and different from a high disease activity group (HDA) in
      short-term outcomes. METHODS: The LDA group was defined as Systemic Lupus
      Erythematosus Disease Activity Index 2000 (SLEDAI-2K) <3, including only 1
      clinical manifestation of rash, alopecia, mucosal ulcers, pleurisy, pericarditis,
      fever, thrombocytopenia, or leukopenia. The patients could be taking
      antimalarials. Remission was defined as no clinical manifestation from taking
      antimalarials alone, and the HDA group was defined as SLEDAI-2K >6. The time
      frame for inclusion in each group was at least 1 year. RESULTS: Of 620 patients
      with active disease who were seen between 1970 and 2015, 80 patients (12.9%)
      fulfilled the criteria for LDA, 191 (30.8%) for remission, and 349 (56.3%) for
      HDA. The LDA patients with and without positive serology results were similar at
      baseline and with prior disease characteristics. After 2 years of followup, the
      LDA and remission groups were similar in their adjusted mean SLEDAI-2K score,
      organ involvement, The Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology Damage Index (SDI) score, mortality, and
      therapies. After 2 and 4 years of followup, the HDA group had a higher adjusted
      mean SLEDAI-2K score, more major organ involvement, a higher SDI score, higher
      mortality, and more therapy compared to the combined LDA/remission groups.
      CONCLUSION: LDA and remission groups had similar short-term outcomes, and both
      had better outcomes and prognosis than the HDA group. LDA may be used as an
      outcome measure in therapeutic trials or in treat-to-target regimens.

PMID- 27696790
TI  - Disease Activity During Pregnancy and the First Year Postpartum in Women With
      Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Disease activity measured by validated methods has been sparsely
      examined during and after pregnancy in women with systemic lupus erythematosus
      (SLE). The aim of this study was to describe the longitudinal course of disease
      activity during pregnancy and the first year postpartum using the Lupus Activity
      Index in Pregnancy (LAI-P). METHODS: RevNatus is a nationwide Norwegian
      prospective observational register including women diagnosed with inflammatory
      rheumatic diseases. LAI-P is a modified version of the LAI, with a good ability
      to assess disease activity in pregnant women with SLE. These indexes were used to
      assess disease activity at 6 visits (in trimesters 1, 2, and 3, and at 6 weeks, 6
      months, and 12 months postpartum). The longitudinal course of disease activity
      was analyzed using an ordinal logistic mixed model. RESULTS: A total of 757
      visits (145 pregnancies) in women with SLE were included in the analysis. More
      than half (51.6%) of the disease activity scores indicated remission, and only
      6.3% indicated moderate disease activity. The model showed a statistically
      significant and clinically relevant change in disease activity over time, and a
      higher disease activity 6 and 12 months postpartum compared to the third
      trimester and 6 weeks postpartum. CONCLUSION: The majority of women had low or no
      disease activity at conception and during pregnancy, with higher disease activity
      at 6 and 12 months after delivery. This points to the importance of tight disease
      control not only before and during pregnancy but also in the first year
      postpartum.

PMID- 27696792
TI  - Immobilization of recombinant pectate lyase from Clostridium thermocellum ATCC
      27405 on magnetic nanoparticles for bioscouring of cotton fabric.
AB  - Recombinant pectate lyase from family 1 polysaccharide lyase (PL1B) was
      immobilized on synthesized magnetic nanoparticles (MNPs) after 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide hydrochloride activation. At 70 mg/mL MNPs 100%
      binding of 1 mg/mL PL1B was achieved. The immobilized PL1B-MNP displayed activity
      of 20.3 and 18.2 U/mg against polygalacturonic acid and citrus pectin,
      respectively, which was higher than the activity of free PL1B, on the same
      substrates of 17.8 and 16.2 U/mg. The immobilized PL1B-MNP showed 32 fold and 14
      fold enhanced thermal stability at 80 degrees C and 90 degrees C, respectively as
      compared with free PL1B at same temperatures. At high temperature the immobilized
      PL1B-MNP retained its activity for a longer duration than free PL1B. The
      immobilized PL1B-MNP could be reused till five cycles and after that it retained
      70% of initial activity. It could be easily recovered from the reaction mixture
      with the help of a magnet. Bioscouring of cotton fabric was carried out with
      immobilized PL1B-MNP which showed efficient removal of pectin from the fabric
      surface. The enhanced wettability of fabric resulted in the decrease of the water
      absorbing time period from 3 min taken by the free PL1B treated fabric to 15 s
      taken by the immobilized PL1B-MNP treated fabric. As per our knowledge this is
      the first attempt of bioscouring of coarse cotton fabric by pectinase immobilized
      on magnetic nanoparticles. (c) 2016 American Institute of Chemical Engineers
      Biotechnol. Prog., 33:231-244, 2017.

PMID- 27696789
TI  - beta-caryophyllene and beta-caryophyllene oxide-natural compounds of anticancer
      and analgesic properties.
AB  - Natural bicyclic sesquiterpenes, beta-caryophyllene (BCP) and beta-caryophyllene
      oxide (BCPO), are present in a large number of plants worldwide. Both BCP and
      BCPO (BCP(O)) possess significant anticancer activities, affecting growth and
      proliferation of numerous cancer cells. Nevertheless, their antineoplastic
      effects have hardly been investigated in vivo. In addition, both compounds
      potentiate the classical drug efficacy by augmenting their concentrations inside
      the cells. The mechanisms underlying the anticancer activities of these
      sesquiterpenes are poorly described. BCP is a phytocannabinoid with strong
      affinity to cannabinoid receptor type 2 (CB2 ), but not cannabinoid receptor type
      1 (CB1 ). In opposite, BCP oxidation derivative, BCPO, does not exhibit CB1/2
      binding, thus the mechanism of its action is not related to endocannabinoid
      system (ECS) machinery. It is known that BCPO alters several key pathways for
      cancer development, such as mitogen-activated protein kinase (MAPK),
      PI3K/AKT/mTOR/S6K1 and STAT3 pathways. In addition, treatment with this compound
      reduces the expression of procancer genes/proteins, while increases the levels of
      those with proapoptotic properties. The selective activation of CB2 may be
      considered a novel strategy in pain treatment, devoid of psychoactive side
      effects associated with CB1 stimulation. Thus, BCP as selective CB2 activator may
      be taken into account as potential natural analgesic drug. Moreover, due to the
      fact that chronic pain is often an element of cancer disease, the double activity
      of BCP, anticancer and analgesic, as well as its beneficial influence on the
      efficacy of classical chemotherapeutics, is particularly valuable in oncology.
      This review is focused on anticancer and analgesic activities of BCP and BCPO,
      the mechanisms of their actions, and potential therapeutic utility.

PMID- 27696793
TI  - Internet Program for Physical Activity and Exercise Capacity in Children With
      Juvenile Idiopathic Arthritis: A Multicenter Randomized Controlled Trial.
AB  - OBJECTIVE: To determine the effects of Rheumates@Work, an internet-based program
      supplemented with 4 group sessions, aimed at improving physical activity,
      exercise capacity, health-related quality of life (HRQoL), and participation in
      children with juvenile idiopathic arthritis. METHODS: Patients were recruited
      from 3 pediatric rheumatology centers in The Netherlands for an observer-blinded,
      randomized controlled multicenter trial. Physical activity level, time spent in
      rest, light, and moderate-to-vigorous physical activity (MVPA) were recorded in a
      diary and with an accelerometer, before intervention, after intervention, and at
      followup after 3 and 12 months (intervention group only). Exercise capacity was
      assessed using the Bruce treadmill protocol, HRQoL was assessed with the
      Pediatric Quality of Life Inventory generic core scale, and participation in
      school and in physical education classes were assessed by questionnaire. RESULTS:
      The intervention group consisted of 28 children, and there were 21 children in
      the control group. MVPA, exercise capacity, and participating in school and
      physical education classes improved significantly in the intervention group.
      HRQoL improved in the control group. No significant differences were found
      between groups. The effect of Rheumates@Work on physical activity and exercise
      capacity lasted during the 12 months of followup. Improvements in physical
      activity were significantly better for the cohort starting in winter compared to
      the summer cohort. CONCLUSION: Rheumates@Work had a positive, albeit small,
      effect on physical activity, exercise capacity, and participation in school and
      physical education class in the intervention group. Improvements lasted for 12
      months. Participants who started in winter showed the most improvement.
      Rheumates@Work had no effect on HRQoL.

PMID- 27696794
TI  - Increased Activity of the Chondrocyte Translational Apparatus Accompanies
      Osteoarthritic Changes in Human and Rodent Knee Cartilage.
AB  - OBJECTIVE: Degeneration of articular cartilage is central to the pathology of
      osteoarthritis (OA). However, the molecular mechanisms leading to these
      irreversible changes are still poorly understood. This study was undertaken to
      investigate how changes in the chondrocyte translational apparatus may contribute
      to the development and progression of knee OA. METHODS: Articular cartilage from
      the knees of normal healthy subjects and patients with OA was used to analyze the
      activity of different components of the translational machinery. Chondrocytes
      isolated from lesional and nonlesional areas of the human OA cartilage were used
      to estimate the relative rate of protein synthesis by metabolic labeling.
      Experimental OA was induced by transection of the anterior cruciate ligament of
      rats to investigate changes in the translational apparatus associated with OA.
      The role of interleukin-1beta (IL-1beta) signaling was assessed in vitro using
      rat articular chondrocytes. In human or rodent knee cartilage, messenger RNA
      expression was analyzed by quantitative polymerase chain reaction, and protein
      levels were determined by immunohistochemistry and Western blotting. RESULTS:
      Several novel traits of OA chondrocytes were identified, including up-regulation
      of the serine/threonine kinases Akt-2 and Akt-3 at the posttranscriptional level
      and an increased rate of total protein synthesis, likely attributable to
      inactivation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1), a
      known repressor of cap-dependent translation. Inactivation of 4E-BP1 was
      dependent on the activity of mechanistic target of rapamycin and was crucial for
      the up-regulation of protein synthesis in general and expression of matrix
      metalloproteinase 13 and ADAMTS-5 in particular. In addition, treatment of
      articular chondrocytes with IL-1beta led to inactivation of 4E-BP1 and up
      regulation of protein synthesis. CONCLUSION: Precise control of protein synthesis
      is vital for cartilage homeostasis, and its dysregulation contributes to the
      molecular pathology of OA. The results of this study therefore identify a novel
      set of potential therapeutic targets to ameliorate the effects of knee OA.

PMID- 27696796
TI  - Two-dimensional fluorescence as soft sensor in the monitoring of
      biotransformation performed by yeast.
AB  - Soft sensors are powerful tools for bioprocess monitoring due to their ability to
      perform online, noninvasive measurement, and possibility of detection of multiple
      components in cultivation media, which in turn can provide tools for the
      quantification of more than one metabolite/substrate/product in real time. In
      this work, soft sensor based on excitation-emission fluorescence is for the first
      time applied for the monitoring of biotransformation production of 2
      phenylethanol (2-PE) by yeast strains. Main process parameters-such as optical
      density, glucose, and 2-PE concentrations-were determined with high accuracy and
      precision by fluorescence fingerprinting coupled with partial least squares
      regression. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog.,
      33:299-307, 2017.

PMID- 27696795
TI  - Relationship Between Attitudes and Beliefs and Physical Activity in Older Adults
      With Knee Pain: Secondary Analysis of a Randomized Controlled Trial.
AB  - OBJECTIVE: To investigate how attitudes and beliefs about exercise relate to
      physical activity behavior in older adults with knee pain attributable to
      osteoarthritis (OA). METHODS: We conducted secondary data analyses of a
      randomized controlled trial of exercise interventions (ISRCTN: 93634563).
      Participants were adults >=45 years old with knee pain attributable to OA (n =
      514). Crude and adjusted cross-sectional and longitudinal associations between
      baseline Self-Efficacy for Exercise (SEE), Positive Outcome Expectations for
      Exercise (POEE), Negative Outcome Expectations for Exercise scores, and physical
      activity level, at baseline, 3 months, and 6 months (measured by self-report
      using the Physical Activity Scale for the Elderly [PASE]), and important
      increases in physical activity level (from baseline to 6-month followup) were
      investigated using multiple linear and logistic regression. RESULTS: Cross
      sectional associations were found between SEE and PASE scores (beta = 4.14 [95%
      confidence interval (95% CI) 0.26, 8.03]) and POEE and PASE scores (beta = 16.71
      [95% CI 1.87, 31.55]), adjusted for sociodemographic and clinical covariates.
      Longitudinal associations were found between baseline SEE and PASE scores at 3
      months (beta = 4.95 [95% CI 1.02, 8.87]) and 6 months beta = 3.71 (0.26, 7.16),
      and baseline POEE and PASE at 3 months (beta = 34.55 [95% CI 20.13, 48.97]) and 6
      months (beta = 25.74 [95% CI 11.99, 39.49]), adjusted for baseline PASE score and
      intervention arm. However, no significant associations with important increases
      in physical activity level were found. CONCLUSION: Greater exercise self-efficacy
      and more positive exercise outcome expectations were associated with higher
      current and future physical activity levels. These may be targets for
      interventions aimed at increasing physical activity.

PMID- 27696797
TI  - In situ Electrochemical Impedance Spectroscopy of Electrostatically Driven
      Selective Gold Nanoparticle Adsorption on Block Copolymer Lamellae.
AB  - Electrostatic attraction between charged nanoparticles and oppositely charged
      nanopatterned polymeric films enables tailored structuring of functional
      nanoscopic surfaces. The bottom-up fabrication of organic/inorganic composites
      for example bears promising potential toward cheap fabrication of catalysts,
      optical sensors, and the manufacture of miniaturized electric circuitry. However,
      only little is known about the time-dependent adsorption behavior and the
      electronic or ionic charge transfer in the film bulk and at interfaces during
      nanoparticle assembly via electrostatic interactions. In situ electrochemical
      impedance spectroscopy (EIS) in combination with a microfluidic system for fast
      and reproducible liquid delivery was thus applied to monitor the selective
      deposition of negatively charged gold nanoparticles on top of positively charged
      poly(2-vinylpyridinium) (qP2VP) domains of phase separated lamellar poly(styrene)
      block-poly(2-vinylpyridinium) (PS-b-qP2VP) diblock copolymer thin films. The
      acquired impedance data delivered information with respect to interfacial charge
      alteration, ionic diffusion, and the charge dependent nanoparticle adsorption
      kinetics, considering this yet unexplored system. We demonstrate that the
      selective adsorption of negatively charged gold nanoparticles (AuNPs) on
      positively charged qP2VP domains of lamellar PS-b-qP2VP thin films can indeed be
      tracked by EIS. Moreover, we show that the nanoparticle adsorption kinetics and
      the nanoparticle packing density are functions of the charge density in the qP2VP
      domains.

PMID- 27696798
TI  - Controlling Shape Anisotropy of ZnS-AgInS2 Solid Solution Nanoparticles for
      Improving Photocatalytic Activity.
AB  - Independently controlling the shape anisotropy and chemical composition of
      multinary semiconductor particles is important for preparing highly efficient
      photocatalysts. In this study, we prepared ZnS-AgInS2 solid solution
      ((AgIn)xZn2(1-x)S2, ZAIS) nanoparticles with well-controlled anisotropic shapes,
      rod and rice shapes, by reacting corresponding metal acetates with a mixture of
      sulfur compounds with different reactivities, elemental sulfur, and 1,3
      dibutylthiourea, via a two-step heating-up process. The chemical composition
      predominantly determined the energy gap of ZAIS particles: the fraction of Zn2+
      in rod-shaped particles was tuned by the ratio of metal precursors used in the
      nanocrystal formation, while postpreparative Zn2+ doping was necessary to
      increase the Zn2+ fraction in the rice-shaped particles. The photocatalytic H2
      evolution rate with irradiation to ZAIS particles dispersed in an aqueous
      solution was significantly dependent on the chemical composition in the case of
      using photocatalyst particles with a constant morphology. In contrast,
      photocatalytic activity at the optimum ZAIS composition, x of 0.35-0.45,
      increased with particle morphology in the order of rice (size: ca. 9 * ca. 16 nm)
      < sphere (diameter: ca. 5.5 nm) < rod (size: 4.6 * 27 nm). The highest apparent
      quantum yield for photocatalytic H2 evolution was 5.9% for rod-shaped ZAIS
      particles, being about two times larger than that obtained with spherical
      particles.

PMID- 27696799
TI  - A high-voltage and non-corrosive ionic liquid electrolyte used in rechargeable
      aluminum battery.
AB  - As a promising post-lithium battery, rechargeable aluminum battery has the
      potential to achieve a three-electron reaction with fully use of metal aluminum.
      Alternative electrolytes are strongly needed for further development of
      rechargeable aluminum batteries, since typical AlCl3-contained imidazole-based
      ionic liquids are moisture sensitive, corrosive, and with low oxidation voltage.
      In this letter, a kind of non-corrosive and water-stable ionic liquid obtained by
      mixing 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM]OTF) with the
      corresponding aluminum salt (Al(OTF)3) is studied. This ionic liquid electrolyte
      has a high oxidation voltage (3.25V vs Al3+/Al) and high ionic conductivity, and
      a good electrochemical performance is also achieved. A new strategy, which first
      use corrosive AlCl3-based electrolyte to construct a suitable passageway on the
      Al anode for Al3+, and then use non-corrosive Al(OTF)3-based electrolyte to get
      stable Al/electrolyte interface, is put forward.

PMID- 27696800
TI  - Influence of Singlet and Charge-Transfer Excitons on the Open-Circuit Voltage of
      Rubrene/Fullerene Organic Photovoltaic Device.
AB  - We demonstrated that the open-circuit voltage (VOC) of rubrene/C60 organic
      photovoltaic (OPV) devices can be substantially improved by changing the rubrene
      thickness. A shoulder exhibited in a range of 500-550 nm was observed. This
      result indicated that the singlet excitons of rubrene were increased when the
      thickness of the rubrene layer was increased. Capacitance-voltage measurements
      were conducted for estimating the built-in potential of the devices. The
      calculated VOC was higher than that of the experiment, thus indicating that
      energetic losses occurred in the devices. We reused the reciprocity and revised
      Marcus theory for determining the charge-transfer (CT) properties of the devices.
      The CT properties of the CT states at the rubrene/C60 interface remained similar.
      The nonradiative energetic losses become smaller when the rubrene layer was
      increased, thus indicating the bimolecular recombination was increased. The
      increased recombination thermally activated the electrons in C60 into rubrene for
      forming the singlet excitons in rubrene. The reduction in reorganization energy
      indicated that the electroluminescence of rubrene was enhanced, thereby improving
      VOC. These results proved that the two-step thermal activation of C60 electrons
      and the improved VOC of rubrene were caused by the increased singlet excitons of
      rubrene.

PMID- 27696801
TI  - Field and Pretreatment-free Detection of Heavy Metal Ions in Organic Polluted
      Water through Alkyne-coded SERS Test Kit.
AB  - Field and pretreatment-free detection of heavy metal ions in organic polluted
      water is important but still challenging in current water pollution emergency
      response system. Here we report a Poly adenine-DNA-mediated approach for
      rationally designed alkyne-coded surface-enhanced Raman scattering (SERS) test
      kit, enabling rapid and simultaneous detection of Hg2+ and Ag+ by portable
      spectrometer, impervious to organic interferences. Due to the formation of
      thymine (T)-Hg2+-T and cytosine (C)-Ag+-C, highly recognizable SERS signals are
      rapidly detected when two different alkynes labeled gold nanoparticles (AuNPs)
      are induced to undergo controllable bridging upon the additive of low volume
      targets. For multiplex detection through portable spectrometer, the limits of
      detection reach 0.77 nM and 0.86 nM for Hg2+ and Ag+, respectively. Of particular
      significance, the proposed C=C contained Raman reporters provide an extremely
      effective solution for multiplex sensing in spectral silent region when the
      hyperspectral and fair intense optical noises originating from lower wave number
      region (<1800 cm-1) are inevitable under complex ambient conditions.

PMID- 27696802
TI  - Robust Multilayered Encapsulation for High-Performance Triboelectric
      Nanogenerator in Harsh Environment.
AB  - Harvesting biomechanical energy especially in vivo is of special significance for
      sustainable powering of wearable/implantable electronics. The triboelectric
      nanogenerator (TENG) is one of the most promising solutions considering its high
      efficiency, low cost, light weight, and easy fabrication, but its performance
      will be greatly affected if there is moisture or liquid leaked into the device
      when applied in vivo. Here, we demonstrate a multiple encapsulation process of
      the TENG to maintain its output performance in various harsh environments.
      Through systematic studies, the encapsulated TENG showed great reliability in
      humid or even harsh environment over 30 days with a stability index of more than
      95%. Given its outstanding reliability, the TENG has the potential to be applied
      in variety of circumstances to function as a sustainable power source for self
      powered biomedical electronics and environmental sensing systems.

PMID- 27696803
TI  - Doping ZnO with Water/Alcohol-Soluble Small Molecules as Electron Transport
      Layers for Inverted Polymer Solar Cells.
AB  - By doping ZnO with porphyrin small molecules (FNEZnP-OE and FNEZnP-T) as cathode
      electron transport layers (ETLs), the inverted polymer solar cells (i-PSC) with
      PTB7:PC71BM (PTB7: polythieno[3,4-b]-thiophene-co-benzodithiophene, PC71BM: [6,
      6]-phenyl-C71-butyric acid methyl ester) as the active materials exhibit enhanced
      device performance. While the power conversion efficiency (PCE) of the PSCs with
      pure ZnO ETL is 7.52%, that of the devices with FNEZnP-T-doped ZnO ETL shows a
      slightly improved PCE of 8.09%, and that of the PSCs with FNEZnP-OE-doped ZnO ETL
      is further enhanced up to 9.24% with an over 20% improvement compared to that
      with pure ZnO ETL. The better performance is contributed by the better
      interfacial contact and reduced work function induced by 9,9-bis(30-(N,N
      dimethylamino)propyl)-2,7-fluorenes and 3,4-bis-(2-(2-methoxy-ethoxy)-ethoxy)
      phenyls in the porphyrin small molecules. More importantly, the PCE is still
      higher than 8% even when the thickness of FNEZnP-OE-doped ZnO ETL is up to 110
      nm, which are important criteria for eventually making organic photovoltaic
      modules with roll-to-roll coat processing.

PMID- 27696804
TI  - Metal-Oxide Stacked Electron Transport Layer for Highly Efficient Inverted
      Quantum-Dot Light Emitting Diodes.
AB  - We report highly efficient inverted quantum-dot light emitting diodes (QLEDs)
      using an Al doped ZnO (AZO)/Li doped ZnO (LZO) stack electron transport layer
      (ETL). An introduction of the LZO layer on AZO improved the current and power
      efficiencies of the green (G-) QLEDs from 10.5 to 34.0 cd A-1 and from 5.4 to
      29.6 lm W-1, respectively. The red (R-), G-, and blue (B-) QLEDs fabricated in
      this work exhibited the maximum external quantum efficiencies (EQEs) of 8.4,
      12.5, and 4.3%, respectively. It is found from time-resolved photoluminescence
      (PL) and transient electroluminescence (EL) decay that exciton loss at the
      interface between the ETL and the emission layer can be significantly reduced by
      introducing LZO.

PMID- 27696805
TI  - Reporter-Embedded SERS Tags from Gold Nanorod Seeds: Selective Immobilization of
      Reporter Molecules at the Tip of Nanorods.
AB  - Reporter embedded (RE) tags are a new generation of sensitive, stable surface
      enhanced Raman scattering (SERS) tags with Raman reporters embedded between gold
      nanoparticle (NP) cores and gold (or silver) shells. Most of the reported RE tags
      have been designed using Au nanospheres as a seed material. Herein, we
      investigated the synthesis and SERS properties of AuNR/reporter/Ag tags by using
      gold nanorod (AuNR) seeds with anisotropic physical and optical features. Several
      highlighted points were discovered, including the following: 1) The
      cetyltrimethylammonium bromide (CTAB) layer induced the co-existence of
      chemically and physically adsorbed Raman reporters on AuNR. Conventional washing
      of the AuNR-reporter complex with water results in the formation of an "internal
      external" mixed tag. To obtain a "pure" RE structure, an additional extraction
      step involving a CTAB solution was essential. 2) The anisotropic distribution of
      CTAB on AuNR resulted in the preference of the Raman reporters to adsorb to the
      hotspot at AuNR tip, which made it a perfect match for improving the SERS signal
      of the tag. 3) An anisotropic silver coating occurred with the shell thickness on
      the AuNR side growing much faster than the shell thickness at the tip. This
      feature ensured that the tag grew to a suitable size with enough silver for SERS
      enhancement without shadowing the effective Raman reporters at the tip too much.
      4) RE tags showed better in vitro and in vivo signal stabilities compared with
      their external labeling counterparts. Moreover, a novel pH-sensitive SERS peak
      test was proposed by using 4-mercaptobenzoic acid as the Raman reporter to verify
      thin coverage by a silver layer. We believe this tag can be broadly applied for
      molecular detection and bio-imaging, and the proposed preparation and structure
      verification methods can provide universal guidance in the design of novel RE
      tags.

PMID- 27696806
TI  - Three-Dimensional Printing of pH-Responsive and Functional Polymers on an
      Affordable Desktop Printer.
AB  - In this work we describe the synthesis, thermal and rheological characterization,
      hot-melt extrusion, and three-dimensional printing (3DP) of poly(2-vinylpyridine)
      (P2VP). We investigate the effect of thermal processing conditions on physical
      properties of produced filaments in order to achieve high quality, 3D-printable
      filaments for material extrusion 3DP (ME3DP). Mechanical properties and
      processing performances of P2VP were enhanced by addition of 12 wt %
      acrylonitrile-butadiene-styrene (ABS), which reinforced P2VP fibers. We 3D-print
      P2VP filaments using an affordable 3D printer. The pyridine moieties are cross
      linked and quaternized postprinting to form 3D-printed pH-responsive hydrogels.
      The printed objects exhibited dynamic and reversible pH-dependent swelling. These
      hydrogels act as flow-regulating valves, controlling the flow rate with pH.
      Additionally, a macroporous P2VP membrane was 3D-printed and the coordinating
      ability of the pyridyl groups was employed to immobilize silver precursors on its
      surface. After the reduction of silver ions, the structure was used to catalyze
      the reduction of 4-nitrophenol to 4-aminophenol with a high efficiency. This is a
      facile technique to print recyclable catalytic objects.

PMID- 27696807
TI  - A Smart Antibacterial Surface Made by Photopolymerization.
AB  - Based on the use of photopolymerization technology, a facile and reliable method
      for in situ preparation of silver nanoparticles (AgNPs) within PNIPAAm functional
      surfaces is presented as a means to achieve non-fouling, antibacterial films. The
      surface properties were characterized by transmission electron microscopy (TEM),
      X-ray photoelectron spectroscopy (XPS), water contact angle and thermogravimetric
      analysis (TGA). The antibacterial and release properties of the surfaces were
      tested against E. coli: at 37 C (above the LCST of PNIPAAm), the functional films
      facilitated the attachment of bacteria, which were then killed by the AgNPs.
      Changing temperature to 4 C (below the LCST), swollen PNIPAAm chains led the
      release of dead bacteria. The results showed that AgNPs/PNIPAAm hybrid surfaces
      offer a "smart" antibacterial capability in response to the change of
      environmental temperature.

PMID- 27696808
TI  - Preparation and Timed Release Properties of Self-Rupturing Gels.
AB  - Swelling of polymeric hydrogels is sensitive to their cross-link densities. Here,
      we exploit this principle to prepare self-rupturing gels which are based on a
      commonly-used, nontoxic, and inexpensive polyelectrolyte, poly(acrylic acid), and
      are prepared through a simple and low-cost polymerization-based technique. The
      self-rupture of these covalently cross-linked gels is achieved by preparing them
      to have highly nonuniform cross-link densities. This heterogeneity in cross
      linking leads to highly nonuniform swelling, which generates stresses that are
      high enough to induce gel rupture. The time required for this rupture to occur
      depends on the difference in the cross-link densities between the adjoining gel
      regions, gel size, order in which the variably cross-linked gel portions are
      synthesized, and on the ambient pH and ionic strength. Furthermore, when these
      self-rupturing gels are prepared to have liquid-filled (capsule-like)
      morphologies, they can act as timed/delayed release devices. The self-rupture of
      these capsules provides a burst payload release after a preprogrammed delay,
      which is on the timescale of days and can be easily tuned by varying the rupture
      time, i.e., by varying either the cross-link nonuniformity or the pH and ionic
      strength of the release media.

PMID- 27696809
TI  - Fouling-Release Performance of Silicone Oil-Modified Siloxane-Polyurethane
      Coatings.
AB  - The effect of incorporation of silicone oils into a siloxane-polyurethane fouling
      release coatings system was explored. Incorporation of phenylmethyl silicone oil
      has been shown to improve the fouling-release performance of silicone-based
      fouling-release coatings through increased interfacial slippage. The extent of
      improvement is highly dependent upon the type and composition of silicone oil
      used. The siloxane-polyurethane (SiPU) coating system is a tough fouling-release
      solution, which combines the mechanical durability of polyurethane while
      maintaining comparable fouling-release performance with regard to commercial
      standards. To further improve the fouling-release performance of the siloxane-PU
      coating system, the use of phenylmethyl silicones oils was studied. Coatings
      formulations were prepared incorporating phenylmethyl silicone oils having a
      range of compositions and viscosities. Contact angle and surface energy
      measurements were conducted to evaluate the surface wettability of the coatings.
      X-ray photoelectron spectroscopy (XPS) depth profiling experiments demonstrated
      self-stratification of silicone oil along with siloxane to the coating-air
      interface. Several coating formulations displayed improved or comparable fouling
      release performance to commercial standards during laboratory biological assay
      tests for microalgae (Navicula incerta), macroalgae (Ulva linza), adult barnacles
      (Balanus amphitrite syn. Amphibalanus amphitrite), and mussels (Geukensia
      demissa). Selected silicone-oil-modified siloxane-PU coatings also demonstrated
      comparable fouling-release performance in field immersion trials. In general,
      modifying the siloxane-PU fouling-release coatings with a small amount (1-5 wt %
      basis) of phenylmethyl silicone oil resulted in improved performance in several
      laboratory biological assays and in long-term field immersion assessments.

PMID- 27696811
TI  - B, N-co-doped graphene supported sulfur for superior stable Li-S half cell and Ge
      S full battery.
AB  - B, N-co-doped graphene supported sulfur (S@BNG) composite is synthesized by using
      melamine diborate as precursor. XPS spectra illustrates that BNG with a high
      percentage and dispersive B, N (B: 13.47 %, N: 9.17 %) and abundant pyridinic-N
      and N-B/N=B bond, which show strong interaction with Li2Sx proved by simulation
      experiments. As cathode for Li-S half cell, S@BNG with a sulfur content of 75 %
      displays a high capacity of 765 mA h g-1 at 1 C even after 500 cycles with a low
      fading rate of 0.027 % per cycle. Even at a high sulfur loading of 4.73 mg cm-2,
      S@BNG still shows a high reversible areal capacity of 3.5 mA h cm-2 after 50
      cycles. When S@BNG composite as cathode combines with high performance lithiated
      Ge anode (discharge capacity of 1138 mA h g-1 at 1 C over 1000 cycles in half
      cell), the assembled Ge-S full battery exhibits a superior capacity of 530 mA h g
      1 at 1 C over 500 cycles.

PMID- 27696810
TI  - Paving the Thermal Highway with Self-Organized Nanocrystals in Transparent
      Polymer Composites.
AB  - Phonon transfer is greatly scattered in traditional polymer composites due to the
      unpaired phonon frequency at the polymer/filler interface. A key innovation of
      this work is to build continuous crystal network by self-organization and utilize
      it as "thermal highway" that circumvents the long-existing interfacial thermal
      barrier issue in traditional composites. By tuning the molecular diffusion rate
      of dicarboxylic acids (oxalic acid, malonic acid, and succinic acid), different
      crystal structures including skeletal, dendrite, diffusion-limited aggregates,
      and spherulite were synthesized in PVA film. These continuous crystal structures
      benefit the efficient phonon transfer in the composites with minimized
      interfacial scattering and lead to a significant thermal conductivity enhancement
      of up to 180% compared to that of pure polymer. Moreover, the transparent feature
      of these composite films provides additional benefits in display applications.
      The post heat treatment effect on the thermal conductivity of the composite films
      shows a time-dependent behavior. These uniquely structured polymer/crystal
      composites are expected to generate significant impacts in thermal management
      applications.

PMID- 27696812
TI  - Interface Engineering of Metal Oxides using Ammonium Anthracene in Inverted
      Organic Solar Cells.
AB  - In this work, by casting water-soluble ammonium anthracene on metal oxides, the
      organic surface modifier re-engineered the interface of the metal oxide to
      improve charge transport. The energy level of ammonium anthracene increased the
      work function of indium tin oxide (ITO), functioning as a hole-blocker (electron
      transporter). Solar cells in which ITO was treated by the ammonium anthracene
      produced an average power conversion efficiency (PCE) of 5.8% without ZnO, the
      electron-transporting layer. When the ammonium anthracene was applied to ZnO, an
      average PCE of 8.1% was achieved, which is higher than the average PCE of 7.5%
      for nontreated ZnO-based devices.

PMID- 27696813
TI  - In-Situ Fabrication of Graphene Oxide Hybrid Ni-Based Metal-Organic Framework (Ni
      MOFs@GO) with Ultrahigh Capacitance as Electrochemical Pseudocapacitor Materials.
AB  - This paper reports a series of novel Ni-based metal-organic framework (Ni-MOFs)
      prepared by a facile solvothermal process. The synthetic conditions have great
      effects on the Ni-MOFs morphologies, porous textures, and their electrochemical
      performance. Improved capacitance performance was successfully realized by the in
      situ hybrid of Ni-MOFs with graphene oxide (GO) nanosheets (Ni-MOFs@GO). The
      pseudocapacitance of ca. 1457.7 F/g for Ni-MOFs obtained at 180  degrees C with
      HCl as the modulator was elevated to ca. 2192.4 F/g at a current density of 1 A/g
      for the Ni-MOFs@GO with GO contents of 3 wt %. Additionally, the capacitance
      retention was also promoted from ca. 83.5% to 85.1% of its original capacitance
      at 10 A/g even after 3000 cycles accordingly. These outstanding electrochemical
      properties of Ni-based MOF materials may be related to their inherent
      characteristics, such as the unique flower-like architecture and fascinating
      synergetic effect between the Ni-MOFs and the GO nanosheets.

PMID- 27696814
TI  - Defect Engineering of Bismuth Oxyiodide by IO3- Doping for Increasing Charge
      Transport in Photocatalysis.
AB  - Defect engineering is regarded as one of the most active projects to regulate the
      chemical and physical properties of materials, which is expected to improve the
      photocatalytic performance of the materials. Herein, oxygen vacancies and IO3-
      doping are introduced into BiOI nanosheets via adding NaH2PO2, which can impact
      the charge carrier dynamics of BiOI photocatalysts, such as its excitation,
      separation, trap, and transfer. These oxygen-deficient BiOI nanosheets display
      excellent photocatalytic activities for degradation of gaseous formaldehyde and
      methyl orange under visible light irradiation, which are 5 and 3.5 times higher
      than the BiOI samples, respectively. Moreover, the oxygen-deficient BiOI also
      have superior cycling stability and can be used for practical application. This
      work did not only develop an effective strategy for fabricating oxygen vacancies
      but also offer a deep insight into the role of oxygen vacancies in enhancing
      photocatalysis.

PMID- 27696815
TI  - A Tale Of Two Luciferins: Fungal and Earthworm New Bioluminescent Systems.
AB  - Bioluminescence, the ability of a living organism to produce light through a
      chemical reaction, is one of Nature's most amazing phenomena widely spread among
      marine and terrestrial species. There are various different mechanisms underlying
      the emission of "cold light", but all involve a small molecule, luciferin, that
      provides energy for light-generation upon oxidation, and a protein, luciferase,
      that catalyzes the reaction. Different species often use different proteins and
      substrates in the process, which suggests that the ability to produce light
      evolved independently several times throughout evolution. Currently, it is
      estimated that there are more than 30 different mechanisms of bioluminescence.
      Even though the chemical foundation underlying the bioluminescence phenomenon is
      by now generally understood, only a handful of luciferins have been isolated and
      characterized. Today, the known bioluminescence reactions are used as
      indispensable analytical tools in various fields of science and technology. A
      pressing need for new bioluminescent analytical techniques with a wider range of
      practical applications stimulates the search and chemical studies of new
      bioluminescent systems. In the past few years two such systems were unraveled:
      those of the earthworms Fridericia heliota and the higher fungi. The luciferins
      of these two systems do not share structural similarity with the previously known
      ones. This Account will survey structure elucidation of the novel luciferins and
      identification of their mechanisms of action. Fridericia luciferin is a key
      component of a novel ATP-dependent bioluminescence system. Structural studies
      were performed on 0.005 mg of natural substance and revealed its unusual
      extensively modified peptidic nature. Elucidation of Fridericia oxyluciferin
      revealed that oxidative decarboxylation of a lysine fragment of luciferin
      supplies energy for light generation, while a fluorescent CompX moiety remains
      intact and serves as a light emitter. Along with luciferin, a number of its
      natural analogs were found in the extracts of worm biomass. They occurred to be
      highly unusual modified peptides comprising a set of amino acids, including
      threonine, aminobutyric acid, homoarginine, unsymmetrical N,N-dimethylarginine
      and extensively modified tyrosine. These natural compounds represent a unique
      peptide chemistry found in terrestrial animals and raise novel questions
      concerning their biosynthetic origin. Also in this Account we discuss
      identification of the luciferin of higher fungi 3-hydroxyhispidin which is
      biosynthesized by oxidation of the precursor hispidin, a known fungal and plant
      secondary metabolite. Furthermore, it was shown that 3-hydroxyhispidin leads to
      bioluminescence in extracts from four diverse genera of luminous fungi, thus
      suggesting a common biochemical mechanism for fungal bioluminescence.

PMID- 27696816
TI  - Correction to Conformational States of HIV-1 Reverse Transcriptase for Nucleotide
      Incorporation vs Pyrophosphorolysis-Binding of Foscarnet.

PMID- 27696817
TI  - Selective Molecularly Mediated Pseudocapacitive Separation of Ionic Species in
      Solution.
AB  - We report the development of a dual-electrode pseudocapacitive separation
      technology (PSST) to capture quantitatively, remotely, and in a reversible manner
      value-added carboxylate salts of environmental and industrial significance. The
      nanostructured pseudocapacitive cell exhibits elegant molecular selectivity
      toward ionic species: upon electrochemical oxidation, a poly(vinylferrocene)
      (PVF)-based anodic electrode shows high selectivity toward carboxylates based on
      their basicity and hydrophobicity. Simultaneously, on the other side of the
      electrochemical cell, a poly(anthraquinone) (PAQ)-based cathodic electrode
      undergoes electrochemical reduction and captures the counterions of these
      carboxylates. The separation and regeneration capability of the electrochemical
      cell was evaluated through the variations in concentration of the carboxylates in
      polar organic solvents (often used in electrocatalytic processes) upon
      electrochemical charging and neutralization of the polymeric cargo of the
      electrodes, respectively. The strong separation efficiency of the system was
      indicated by its ability to capture an individual carboxylate (acetate, formate,
      or benzoate) selectively over other competing ions present in solution in
      significant excess, with an electrosorption capacity in the range of 122-157 mg
      anions/gcell (polymer and CNT components on the anodic and cathodic side of the
      cell). The ion sorption capacity of the cell was high even after five
      adsorption/desorption cycles (18 000 s of continuous operation). In addition, the
      cell exhibited molecular selectivity even between two carboxylates (e.g., between
      benzoate and acetate or formate) which differ only in terms of basicity and
      hydrophobicity. We anticipate that this strategy can be employed as a versatile
      platform for selective ion separations. In particular, the functionalization of
      electrochemical cells with the proper polymers would enable the remote and
      economically viable electro-mediated separation of the desired ionic species in a
      quantitative and reversible manner.

PMID- 27696818
TI  - Homodimeric Escherichia coli Toxin CcdB (Controller of Cell Division or Death B
      Protein) Folds via Parallel Pathways.
AB  - The existence of parallel pathways in the folding of proteins seems intuitive,
      yet remains controversial. We explore the folding kinetics of the homodimeric
      Escherichia coli toxin CcdB (Controller of Cell Division or Death B protein)
      using multiple optical probes and approaches. Kinetic studies performed as a
      function of protein and denaturant concentrations demonstrate that the folding of
      CcdB is a four-state process. The two intermediates populated during folding are
      present on parallel pathways. Both form by rapid association of the monomers in a
      diffusion limited manner and appear to be largely unstructured, as they are
      silent to the optical probes employed in the current study. The existence of
      parallel pathways is supported by the insensitivity of the amplitudes of the
      refolding kinetic phases to the different probes used in the study. More
      importantly, interrupted refolding studies and ligand binding studies clearly
      demonstrate that the native state forms in a biexponential manner, implying the
      presence of at least two pathways. Our studies indicate that the CcdA antitoxin
      binds only to the folded CcdB dimer and not to any earlier folding intermediates.
      Thus, despite being part of the same operon, the antitoxin does not appear to
      modulate the folding pathway of the toxin encoded by the downstream cistron. This
      study highlights the utility of ligand binding in distinguishing between
      sequential and parallel pathways in protein folding studies, while also providing
      insights into molecular interactions during folding in Type II toxin-antitoxin
      systems.

PMID- 27696819
TI  - Putative Receptor Binding Domain of Bat-Derived Coronavirus HKU9 Spike Protein:
      Evolution of Betacoronavirus Receptor Binding Motifs.
AB  - The suggested bat origin for Middle East respiratory syndrome coronavirus (MERS
      CoV) has revitalized the studies of other bat-derived coronaviruses with respect
      to interspecies transmission potential. Bat coronavirus (BatCoV) HKU9 is an
      important betacoronavirus (betaCoV) that is phylogenetically affiliated with the
      same genus as MERS-CoV. The bat surveillance data indicated that BatCoV HKU9 has
      been widely spreading and circulating in bats. This highlights the necessity of
      characterizing the virus for its potential to cross species barriers. The
      receptor binding domain (RBD) of the coronavirus spike (S) protein recognizes
      host receptors to mediate virus entry and is therefore a key factor determining
      the viral tropism and transmission capacity. In this study, the putative S RBD of
      BatCoV HKU9 (HKU9-RBD), which is homologous to other betaCoV RBDs that have been
      structurally and functionally defined, was characterized via a series of
      biophysical and crystallographic methods. By using surface plasmon resonance, we
      demonstrated that HKU9-RBD binds to neither SARS-CoV receptor ACE2 nor MERS-CoV
      receptor CD26. We further determined the atomic structure of HKU9-RBD, which as
      expected is composed of a core and an external subdomain. The core subdomain fold
      resembles those of other betaCoV RBDs, whereas the external subdomain is
      structurally unique with a single helix, explaining the inability of HKU9-RBD to
      react with either ACE2 or CD26. Via comparison of the available RBD structures,
      we further proposed a homologous intersubdomain binding mode in betaCoV RBDs that
      anchors the external subdomain to the core subdomain. The revealed RBD features
      would shed light on the evolution route of betaCoV.

PMID- 27696821
TI  - Use of Pulsed Streaming Potential with a Prepared Cationic Polyelectrolyte Layer
      to Detect Deposition Kinetics of Graphene Oxide and Consequences of Particle Size
      Differences.
AB  - The deposition kinetics of graphene oxide (GO) onto poly(ethylene imine) (PEI)
      layer was characterized in situ with pulsed streaming potential (SP) measurement,
      and it was found that the initial rate constant (ki) was dependent on the size of
      GO with same surface charge density at a fixed concentration under controlled
      experimental conditions. Assuming the deposition was controlled by diffusion at
      the initial stage, ki is proportional to Rh-2/3, where Rh is the hydrodynamic
      radius. By flushing a GO solution through a capillary coated with PEI, the
      initial change rate of relative SP (dEr/dt) was obtained in 20 s and ki was
      measured with five different concentrations in about 2 min. Three GO samples of
      different sizes obtained from the same batch of raw material were characterized
      with pulsed SP to get ki values, and their sizes were verified with atomic force
      microscopy and dynamic light scattering. The experimental results are consistent
      with the predicted effects of the size of NPs on their deposition kinetics.

PMID- 27696820
TI  - Virus-like Particle Display of the alpha-Gal Epitope for the Diagnostic
      Assessment of Chagas Disease.
AB  - The alpha-Gal antigen [Galalpha(1,3)Galbeta(1,4)GlcNAcalpha] is an immunodominant
      epitope displayed by infective trypomastigote forms of Trypanosoma cruzi, the
      causative agent of Chagas disease. A virus-like particle displaying a high
      density of alpha-Gal was found to be a superior reagent for the ELISA-based
      serological diagnosis of Chagas disease and the assessment of treatment
      effectiveness. A panel of sera from patients chronically infected with T. cruzi,
      both untreated and benznidazole-treated, was compared with sera from patients
      with leishmaniasis and from healthy donors. The nanoparticle-alpha-Gal construct
      allowed for perfect discrimination between Chagas patients and the others,
      avoiding false negative and false positive results obtained with current state-of
      the-art reagents. As previously reported with purified alpha-Gal-containing
      glycosylphosphatidylinositol-anchored mucins, the current study also showed
      concentrations of anti-alpha-Gal IgG to decrease substantially in patients
      receiving treatment with benznidazole, suggesting that the semiquantitative
      assessment of serum levels of this highly abundant type of antibody can report on
      disease status in individual patients.

PMID- 27696822
TI  - Self-Assembled Peptide-Based System for Mitochondrial-Targeted Gene Delivery:
      Functional and Structural Insights.
AB  - Human mitochondrial dysfunction can lead to severe and often deadly diseases, for
      which there are no known cures. Although the targeted delivery of therapeutic
      gene to mitochondria is a promising approach to alleviate these disorders, gene
      carrier systems for the selective delivery of functional DNA into the
      mitochondria of living mammalian cells are currently unavailable. Here we
      rationally developed dual-domain peptides containing DNA-condensing/cell
      penetrating/endosome-disruptive and mitochondria-targeting sequences. Secondary
      structures of the dual-domain peptides were analyzed, and variations in the
      physicochemical properties (stability, size, and zeta potential) of peptide/DNA
      complexes were studied as a function of peptide-to-DNA ratio and serum addition.
      An optimized formulation, identified through qualitative and quantitative
      studies, fulfills the fundamental prerequisites for mitochondria-specific DNA
      delivery, successfully transfecting a high proportion (82 +/- 2%) of mitochondria
      in a human cell line with concomitant biocompatibility. Nuclear magnetic
      resonance studies confirmed the effectiveness of our bipartite peptide design
      with segregated functions: a helical domain necessary for mitochondrial import
      and an unstructured region for interaction with DNA involving lysine residues.
      Further analyses revealed that the lysine-specific interaction assisted the self
      organization of the peptide and the DNA cargo, leading to a structural
      arrangement within the formed complex that is crucial for its biological
      efficiency. Thus the reported gene vector represents a new and reliable tool to
      uncover the complexity of mitochondrial transfection.

PMID- 27696823
TI  - Pore-Free Matrix with Cooperative Chelating of Hyperbranched Ligands for High
      Performance Separation of Uranium.
AB  - A new strategy combining a pore-free matrix and cooperative chelating was
      proposed in the present paper in order to effectively avoid undesired
      nonselective physical adsorption and intraparticle diffusion caused by pores and
      voids in porous sorbents, and to greatly enhance uranium-chelating capability
      based on hyperbranched amidoxime ligands on the surface of nanodiamond particles.
      Thus, a pore-free, amidoxime-terminated hyperbranched nanodiamond (ND-AO) was
      designed and synthesized. The experimental results demonstrate that the strategy
      endows the as-synthesized ND-AO with the following expected features: (1)
      distinctively high uranium selectivity (SU = qe-U/qe-tol * 100%) from over 80% to
      nearly 100% over the whole weak acidity range (pH < 4.5); especially, the SU can
      reach up to unprecedented >91% at pH 4.5, more than 20% of selectivity increment
      over any analogous sorbent materials reported so far, with a uranium sorption
      capacity of 121 mg/g in simulated nuclear industry effluent samples containing 12
      coexistent nuclide ions; (2) superfast equilibrium sorption time of <30 s; and
      (3) one of the highest distribution coefficients (Kd) of ~3 * 106 mL/g for U(VI)
      as well as a fairly high sorption capacity of 212 mg/g at pH 4.5 in pure uranium
      solution. The strategy could also provide an optional approach for the design and
      fabrication of other new high-performance sorbing materials with prospective
      applications in selective separation of other interested metal ions.

PMID- 27696825
TI  - Controlled Delivery of Extracellular ROS Based on Hematoporphyrin-Incorporated
      Polyurethane Film for Enhanced Proliferation of Endothelial Cells.
AB  - The principle of photodynamic treatment (PDT) involves the administration of
      photosensitizer (PS) at diseased tissues, followed by light irradiation to
      produce reactive oxygen species (ROS). In cells, a moderate increase in ROS plays
      an important role as signaling molecule to promote cell proliferation, whereas a
      severe increase of ROS causes cell damage. Previous studies have shown that low
      levels of ROS stimulate cell growth through PS drugs-treating PDT and nonthermal
      plasma treatment. However, these methods have side effects which are associated
      with low tissue selectivity and remaining of PS residues. To overcome such
      shortcomings, we designed hematoporphyrin-incorporated polyurethane (PU) film
      induced generation of extracellular ROS with singlet oxygen and free radicals.
      The film can easily control ROS production rate by regulating several parameters
      including light dose, PS dose. Also, its use facilitates targeted delivery of ROS
      to the specific lesion. Our study demonstrated that extracellular ROS could
      induce the formation of intracellular ROS. In vascular endothelial cells, a
      moderated increase in intracellular ROS also stimulated cell proliferation and
      cell cycle progression by accurate control of optimum levels of ROS with
      hematoporphyrin-incorporated polymer films. This modulation of cellular growth is
      expected to be an effective strategy for the design of next-generation PDT.

PMID- 27696824
TI  - Maintenance and Function of a Plant Chromosome in Human Cells.
AB  - Replication, segregation, gene expression, and inheritance are essential features
      of all eukaryotic chromosomes. To delineate the extent of conservation of
      chromosome functions between humans and plants during evolutionary history, we
      have generated the first human cell line containing an Arabidopsis chromosome.
      The Arabidopsis chromosome was mitotically stable in hybrid cells following cell
      division, and initially existed as a translocated chromosome. During culture, the
      translocated chromosomes then converted to two types of independent plant
      chromosomes without human DNA sequences, with reproducibility. One pair of
      localization signals of CENP-A, a marker of functional centromeres was detected
      in the Arabidopsis genomic region in independent plant chromosomes. These results
      suggest that the chromosome maintenance system was conserved between human and
      plants. Furthermore, the expression of plant endogenous genes was observed in the
      hybrid cells, implicating that the plant chromosomal region existed as
      euchromatin in a human cell background and the gene expression system is
      conserved between two organisms. The present study suggests that the essential
      chromosome functions are conserved between evolutionarily distinct organisms such
      as humans and plants. Systematic analyses of hybrid cells may lead to the
      production of a shuttle vector between animal and plant, and a platform for the
      genome writing.

PMID- 27696826
TI  - Sulforhodamine Nanothermometer for Multiparametric Fluorescence Lifetime Imaging
      Microscopy.
AB  - Live cells function within narrow limits of physiological temperature (T) and O2
      and metabolite concentrations. We have designed a cell-permeable T-sensitive
      fluorescence lifetime-based nanoprobe based on lipophilic sulforhodamine, which
      stains 2D and 3D cell models, shows cytoplasmic localization, and has a robust
      response to T (~0.037 ns/K). Subsequently, we evaluated the probe and
      fluorescence lifetime imaging microscopy (FLIM) technique for combined imaging of
      T and O2 gradients in metabolically active cells. We found that in adherent 2D
      culture of HCT116 cells intracellular T and O2 are close to ambient values.
      However, in 3D spheroid structures having size >200 MUm, T and O2 gradients
      become pronounced. These microgradients can be enhanced by treatment with
      mitochondrial uncouplers or dissipated by drug-induced disaggregation of the
      spheroids. Thus, we demonstrate the existence of local microgradients of T in 3D
      cell models and utility of combined imaging of O2 and T.

PMID- 27696827
TI  - Detection of Ligand-Induced Conformational Changes in Oligonucleotides by Second
      Harmonic Generation at a Supported Lipid Bilayer Interface.
AB  - There is a high demand for characterizing oligonucleotide structural changes
      associated with binding interactions as well as identifying novel binders that
      modulate their structure and function. In this study, second-harmonic generation
      (SHG) was used to study RNA and DNA oligonucleotide conformational changes
      associated with ligand binding. For this purpose, we developed an avidin-based
      biotin capture surface based on a supported lipid bilayer membrane. The technique
      was applied to two well-characterized aptamers, both of which undergo
      conformational changes upon binding either a protein or a small molecule ligand.
      In both cases, SHG was able to resolve conformational changes in these
      oligonucleotides sensitively and specifically, in solution and in real time,
      using nanogram amounts of material. In addition, we developed a competition assay
      for the oligonucleotides between the specific ligands and known, nonspecific
      binders, and we demonstrated that intercalators and minor groove binders affect
      the conformation of the DNA and RNA oligonucleotides in different ways upon
      binding and subsequently block specific ligand binding in all cases. Our work
      demonstrates the broad potential of SHG for studying oligonucleotides and their
      conformational changes upon interaction with ligands. As SHG offers a powerful,
      high-throughput screening approach, our results here also open an important new
      avenue for identifying novel chemical probes or sequence-targeted drugs that
      disrupt or modulate DNA or RNA structure and function.

PMID- 27696828
TI  - Structural Studies of a Complex Between Endothelial Nitric Oxide Synthase and
      Calmodulin at Physiological Calcium Concentration.
AB  - The small acidic protein Calmodulin (CaM) serves as a Ca2+ sensor and control
      element for many enzymes including nitric oxide synthase (NOS) enzymes that play
      major roles in key physiological and pathological processes. CaM binding causes a
      conformational change in NOS to allow for the electron transfer between the
      reductase and oxygenase domains through a process that is thought to be highly
      dynamic. In this report, NMR spectroscopy was used to determine the solution
      structure of the endothelial NOS (eNOS) peptide in complex with CaM at the lowest
      Ca2+ concentration (225 nM) required for CaM to bind to eNOS and corresponds to a
      physiological elevated Ca2+ level found in mammalian cells. Under these
      conditions, the CaM-eNOS complex has a Ca2+-replete C-terminal lobe bound the
      eNOS peptide and a Ca2+ free N-terminal lobe loosely associated to the eNOS
      peptide. With increasing Ca2+ concentration, the binding of Ca2+ by the N-lobe of
      CaM results in a stronger interaction with the C-terminal region of the eNOS
      peptide and increased alpha-helical structure of the peptide that may be part of
      the mechanism resulting in electron transfer from the FMN to the heme in the
      oxygenase domain of the enzyme. SPR studies performed under the same conditions
      show Ca2+ concentration dependent binding kinetics were consistent with the NMR
      structural results. This investigation shows that structural studies performed
      under more physiological relevant conditions provide information on subtle
      changes in structure that may not be apparent when experiments are performed in
      excess Ca2+ concentrations.

PMID- 27696829
TI  - Deconstructing Methane Emissions from a Small Northern European River:
      Hydrodynamics and Temperature as Key Drivers.
AB  - Methane (CH4) emissions from small rivers and streams, particularly via
      ebullition, are currently under-represented in the literature. Here, we quantify
      the methane effluxes and drivers in a small, Northern European river. Methane
      fluxes are comparable to those from tropical aquatic systems, with average
      emissions of 320 mg CH4 m-2 d-1. Two important drivers of methane flux variations
      were identified in the studied system: 1) temperature-driven sediment methane
      ebullition and 2) flow-dependent contribution suspected to be hydraulic exchange
      with adjacent wetlands and small side-bays. This flow-dependent contribution to
      river methane loading is shown to be negligible for flows less than 4 m3 s-1 and
      greater than 50% as flows exceed 7 m3 s-1. While the temperature-ebullition
      relationship is comparable to other systems, the flow rate dependency has not
      been previously demonstrated. In general, we found that about 80% of the total
      emissions were due to methane bubbles. Applying ebullition rates to global
      estimates for fluvial systems, which currently are not considered, could
      dramatically increase emission rates to ranges from lakes or wetlands. This work
      illustrates that small rivers can emit significant methane and highlights the
      need for further studies on the link between hydrodynamics and connected
      wetlands.

PMID- 27696830
TI  - Effect of Biodiesel Fuels on Real-World Emissions of Passenger Locomotives.
AB  - Few data are available regarding the effect of biodiesel on exhaust emission
      rates of two-stroke engines used in many passenger locomotives. Using a portable
      emissions measurement system (PEMS), duty cycle average nitrogen oxides (NOx),
      hydrocarbons (HC), carbon monoxide (CO), particulate matter (PM), and carbon
      dioxide (CO2) emission rates were measured for three locomotives operating on
      ultra-low sulfur diesel (ULSD) and soy-based B10, B20, and B40 biodiesel blends.
      Measurements were conducted in the rail yard (RY) and over-the-rail (OTR) during
      passenger service. Compared to ULSD, B20 biodiesel had statistically significant
      average emission rate reductions in the RY of 58% for CO, 45% for PM, and 6% CO2
      and OTR of 59% for HC, 50% for CO, 26% for PM, and 5% for CO2. The average
      differences in NOx emission rates for both the RY and OTR, and HC in the RY, were
      not statistically significant. The OTR findings typically agreed qualitatively
      with the RY findings; however, OTR provides a better basis for estimating the
      real-world impact of fuel switching. The results indicate substantial potential
      to reduce in-use locomotive emissions for existing older locomotives, with the
      exception of NOx.

PMID- 27696831
TI  - Synthesis and Magnetic Characterization of Fe(III)-Based 9-Metallacrown-3
      Complexes Which Exhibit Magnetorefrigerant Properties.
AB  - The structural characterization and magnetic properties of three related 9
      metallacrown-3 (9-MC-3) structures are reported. Each of these iron complexes is
      shown to exhibit significant magnetic refrigerant properties. FeIII(acetate)3[9
      MCFeIIIN(shi)-3](MeOH)3.MeOH.7H2O (1-OAc) and FeIII(benzoate)3[9-MCFeIIIN(shi)
      3](MeOH)3.MeOH.4H2O (1-OBz) are structurally analogous tetranuclear iron(III)
      clusters which exhibit drastically different magnetic properties, due to
      differences in intermolecular and intramolecular pi interactions which affect
      superexchange. 1-OAc displays a magnetocaloric effect with a maximum entropy
      change of -DeltaSm = 15.4 J kg-1 K-1 at T = 3 K and an applied field change of
      MUoDeltaH = 7 T, whereas 1-OBz exhibits a maximum -DeltaSm = 7.4 J kg-1 K-1 at T
      = 7 K and MUoDeltaH = 7 T and displays an inverse magnetocaloric effect at lower
      temperatures and field changes. 1-OAc has -DeltaSm values comparable to those of
      other Fe-based MCE materials and displays a significant MCE at lower applied
      fields, with -DeltaSm = 11.2 J kg-1 K-1 at 3 K and MUoDeltaH = 3 T. The
      tetranuclear core of 1 may be linked with isophthalate to form an octanuclear
      FeIII2(isophthalate)3[9-MCFeIIIN(shi)-3]2 dimer (2) that crystallizes in a
      honeycomb packing arrangement and exhibits solvation-dependent magnetic
      properties. The MCE for this molecule ranges from -DeltaSm = 9.9 J kg-1 K-1 at T
      = 5 K and MUoDeltaH = 7 T, when the pores of the material are highly occupied
      with solvent, to -DeltaSm = 5.4 J kg-1 K-1, when the system is fully desolvated.

PMID- 27696832
TI  - Aluminum-Cycle Ion Exchange Process for Hardness Removal: A New Approach for
      Sustainable Softening.
AB  - From a sustainability viewpoint, sodium exchange softening, although used widely,
      is under scrutiny due to its production of excess Na-laden spent regenerant and
      subsequent discharge to the environment. Many arid regions are introducing
      regulations disallowing dumping of concentrated sodium salts, the residuals from
      popular Na-exchange softening. The sodium content of the softened water is, also,
      always higher than in the feed, which poses a dietary health concern when used
      for drinking or cooking. An efficient, easy-to-operate hardness removal process
      with reduced sodium in both the treated water and in the spent regenerant is an
      unmet global need. Use of a cation exchange resin in Al3+-form for hardness
      removal, that is, exchange of divalent Ca2+ or Mg2+ with trivalent Al3+, is
      counterintuitive, and this is particularly so, because the aluminum ion to be
      exchanged has higher affinity than calcium. Nevertheless, ion exchange
      accompanied by precipitation of aluminum hydroxide allows progress of the cation
      exchange reaction leading to hardness removal. Experimental results demonstrated
      that calcium can be consistently removed for multiple cycles using a
      stoichiometric amount of AlCl3 as the regenerant. The process essentially
      operates at the maximum possible thermodynamic efficiency: removal of one
      equivalent of Ca2+ corresponds to use of one equivalent of Al3+ as a regenerant.
      During the Al-cycle process there is no increase in Na+ concentration and partial
      reduction in the total dissolved solids (TDS) of the treated water. It is
      noteworthy that the ion-exchange resin used, components of the fixed-bed column
      and operational protocol are nearly the same as traditional softening processes
      on Na-cycle. Thus, existing Na-cycle systems can be retrofitted into Al-cycle
      operation without major difficulty.

PMID- 27696833
TI  - In-Plate and On-Plate Structural Control of Ultra-Stable Gold/Silver Bimetallic
      Nanoplates as Redox Catalysts, Nanobuilding Blocks, and Single-Nanoparticle
      Surface-Enhanced Raman Scattering Probes.
AB  - Noble metal bimetallic nanomaterials have attracted a great deal of attention
      owing to the strong correlation between their morphology and chemical and
      physical properties. Even though the synthetic strategies for controlling the
      shapes of monometallic nanomaterials such as gold (Au) and silver (Ag) are well
      developed, limited advances have been made with Au/Ag bimetallic nanomaterials to
      date. In this work, we demonstrate a highly complex in-plate and on-plate
      structural control of Au/Ag bimetallic nanoplates (Au/AgBNPLs) in contrast to
      conventional, simply structured, 1D and 2D, branched, and polyhedral
      nanomaterials. The polymer used in the synthesis of seeds plays a critical role
      in controlling the structure of the Au/AgBNPLs. The Au/AgBNPLs exhibit
      exceptionally high chemical stability against various chemical etchants and a
      versatile catalytic reactivity with biologically and environmentally relevant
      chemical species. Significantly, the reversible assembly formation of the
      Au/AgBNPLs is demonstrated by carrying out the surface-functionalization of the
      materials with thiol DNA, emphasizing the potential applications of the
      Au/AgBNPLs in various diagnostic and therapeutic purposes. Finally, the surface
      enhanced Raman scattering (SERS) properties of the Au/AgBNPLs are experimentally
      and theoretically investigated, demonstrating a substantial potential of the
      Au/AgBNPLs as single-nanoparticle SERS probes. Electron microscopy, UV-vis
      spectroscopy, selected area electron diffraction (SAED), and energy-dispersive X
      ray (EDX) spectroscopy are employed to analyze the structure and composition of
      the Au/AgBNPLs at the atomic level.

PMID- 27696835
TI  - Effect of H-Bonding on Order Amplification in the Growth of a Supramolecular
      Polymer in Water.
AB  - While a great deal of knowledge on the roles of hydrogen bonding and
      hydrophobicity in proteins have resulted in the creation of rationally designed
      and functional peptidic structures, the roles of these forces on purely synthetic
      supramolecular architectures in water have proven difficult to ascertain.
      Focusing on a 1,3,5-benzenetricarboxamide (BTA) based supramolecular polymer, we
      have designed a molecular modeling strategy to dissect the energetic
      contributions involved in the self-assembly (electrostatic, hydrophobic, etc.)
      upon growth of both ordered BTA stacks and random BTA aggregates. Utilizing this
      set of simulations, we have unraveled the cooperative mechanism for polymer
      growth, where a critical size must be reached in the aggregates before emergence
      and amplification of order into the experimentally observed fibers. Furthermore,
      we have found that the formation of ordered fibers is favored over disordered
      aggregates solely on the base of electrostatic interactions. Detailed analysis of
      the simulation data suggests that H-bonding is a major source of this
      stabilization energy. Experimental and computational comparison with a newly
      synthesized 1,3,5-benzenetricarboxyester (BTE) derivative, lacking the ability to
      form the H-bonding network, demonstrated that this BTE variant is also capable of
      fiber formation, albeit at a reduced persistence length. This work provides
      unambiguous ev-idence for the key 1D driving force of hydrogen bonding in
      enhancing the persistency of monomer stacking and amplifying the lev-el of order
      into the growing supramolecular polymer in water. Our computational approach
      provides an important relationship di-rectly linking the structure of the monomer
      to the structure and properties of the supramolecular polymer.

PMID- 27696834
TI  - Combining Leaching and Passive Sampling To Measure the Mobility and Distribution
      between Porewater, DOC, and Colloids of Native Oxy-PAHs, N-PACs, and PAHs in
      Historically Contaminated Soil.
AB  - Different methods to quantify soil porewater concentrations of contaminants will
      provide different types of information. Passive sampling measurements give freely
      dissolved porewater concentrations (Cpw,free), while leaching tests provide
      information on the mobile concentration (Cpw,leach), including contaminants
      associated with dissolved organic carbon (DOC) and particles/colloids in the
      porewater. This study presents a novel combination of these two measurements, to
      study the sorption and mobility of polycyclic aromatic compounds (PACs) to DOC
      and particulate organic carbon (POC) in 10 historically contaminated soils. The
      PACs investigated were polycyclic aromatic hydrocarbons (PAHs), oxygenated-PAHs,
      and nitrogen containing heterocyclic PACs. Observed Cpw,leach was up to 5 orders
      of magnitude higher than Cpw,free; implying large biases when Cpw,leach is used
      to assess bioavailability or soil partitioning. Sorption of PACs to DOC and POC
      was important for the mobility of compounds with log KOW > 4. Average DOC/water
      partitioning coefficients (KDOC) correlated well with KOW (log KDOC = 0.89 * log
      KOW +1.03 (r2 = 0.89)). This relationship is likely more accurate for
      historically contaminated soils than previously published data, which suffer from
      artifacts caused by problems in measuring Cpw,free correctly or not using
      historically contaminated soils. POC/water-partitioning coefficients (KPOC) were
      orders of magnitude larger than corresponding KDOC, suggesting sorption to mobile
      particles/colloids is the dominant mechanism for PAC mobility.

PMID- 27696836
TI  - Regioselective Atomic Layer Deposition in Metal-Organic Frameworks Directed by
      Dispersion Interactions.
AB  - The application of atomic layer deposition (ALD) to metal-organic frameworks
      (MOFs) offers a promising new approach to synthesize designer functional
      materials with atomic precision. While ALD on flat substrates is well
      established, the complexity of the pore architecture and surface chemistry in
      MOFs present new challenges. Through in situ synchrotron X-ray powder
      diffraction, we visualize how the deposited atoms are localized and redistribute
      within the MOF during ALD. We demonstrate that the ALD is regioselective, with
      preferential deposition of oxy-Zn(II) species within the small pores of NU-1000.
      Complementary density functional calculations indicate that this startling
      regioselectivity is driven by dispersion interactions associated with the
      preferen-tial adsorption sites for the organometallic precursors prior to
      reaction.

PMID- 27696837
TI  - Kinetic studies of Pt carbonate mediated, room temperature, oxidation of carbon
      monoxide by oxygen over Pt/Al2O3 using combined, time resolved, XAFS, DRIFTS and
      mass spectrometry.
AB  - The kinetics involved in a recently revealed ambient temperature mechanism for
      the catalytic oxidation of carbon monoxide by oxygen over a 5 wt% Pt/Al2O3
      catalyst are evaluated within a periodic, plug flow, redox operation paradigm
      using combined mass spectrometry (MS), diffuse reflectance infrared spectroscopy
      (DRIFTS) and time resolved Pt L3 edge XAFS. DRIFTS demonstrates that the most
      active species is a high wavenumber (ca. 1685 cm-1) carbonate that we associate
      directly with a room temperature redox process (as observed with XAFS) occurring
      on a fraction of the Pt atoms. Pt carbonate formation (1685 cm-1) under CO and
      reaction to yield CO2 is shown to be extremely rapid and subject to an average
      apparent activation energy (Eapp), across the techniques applied, of 8.7 kJ mol
      1, within the temperature range investigated (276 - 343 K). Re-oxidation of Pt
      (XANES) and subsequent CO2 production mediated by Pt carbonates under O2 (MS/IR)
      displays a first order dependence upon O2 partial pressure and a negative
      dependence upon the coverage of CO adsorbed upon the Pt nanoparticles also
      present in this catalyst. This oxidative regeneration/CO2 production step is
      subject to an apparent activation energy (Eapp) of 56.5 (+/-5) kJ mol-1 and is
      kinetically limited by desorption of molecular CO from Pt nanoparticles. This
      process is also subject to an induction time that depends upon the partial
      pressure of O2 indicative of a direct interaction of O2 with molecular CO
      adsorbed on the nanoparticles that promotes CO desorption. Lastly, a minority
      reactive state producing CO2 in the oxidising cycle that displays no dependence
      upon the CO coverage of the nanoparticles can be induced through simple thermal
      treatment of the catalyst. These results are discussed in terms of the number and
      types of species present within the reactive system and in terms of the wider
      possibilities for the development of effective low temperature CO oxidation using
      Pt/Al2O3 catalysts.

PMID- 27696838
TI  - Commute Maps: Separating Slowly Mixing Molecular Configurations for Kinetic
      Modeling.
AB  - Identification of the main reaction coordinates and building of kinetic models of
      macromolecular systems require a way to measure distances between molecular
      configurations that can distinguish slowly interconverting states. Here we define
      the commute distance that can be shown to be closely related to the expected
      commute time needed to go from one configuration to the other, and back. A
      practical merit of this quantity is that it can be easily approximated from
      molecular dynamics data sets when an approximation of the Markov operator
      eigenfunctions is available, which can be achieved by the variational approach to
      approximate eigenfunctions of Markov operators, also called variational approach
      of conformation dynamics (VAC) or the time-lagged independent component analysis
      (TICA). The VAC or TICA components can be scaled such that a so-called commute
      map is obtained in which Euclidean distance corresponds to the commute distance,
      and thus kinetic models such as Markov state models can be computed based on
      Euclidean operations, such as standard clustering. In addition, the distance
      metric gives rise to a quantity we call total kinetic content, which is an
      excellent score to rank input feature sets and kinetic model quality.

PMID- 27696841
TI  - Wavelength Selective Generation of Aryl Radicals and Aryl Cations for Metal-Free
      Photoarylations.
AB  - Photochemical reactions have become an important tool for organic chemists.
      Visible (solar) light can be conveniently adopted, however, only when using
      colored organic compounds or in photocatalyzed processes induced by visible light
      absorbing photocatalysts. Herein we demonstrate that a photolabile, colored
      moiety could be incorporated in a colorless organic compound with the aim of
      generating highly reactive intermediates upon exposure to visible (solar) light.
      Arylazo sulfones, colored thermally stable derivatives of aryl diazonium salts,
      were used as valuable substrates for the photoinduced metal-free synthesis of
      (hetero)biaryls with no need of a (photo)catalyst or of other additives to
      promote the reaction. Noteworthy, selective generation of aryl radicals and aryl
      cations can be attained at will by varying the irradiation conditions (visible
      light for the former and UVA light for the latter).

PMID- 27696839
TI  - Novel Potent Proline-Based Metalloproteinase Inhibitors: Design,
      (Radio)Synthesis, and First in Vivo Evaluation as Radiotracers for Positron
      Emission Tomography.
AB  - As dysregulation of matrix metalloproteinase (MMP) activity is associated with a
      wide range of pathophysiological processes like cancer, atherosclerosis, and
      arthritis, MMPs represent a valuable target for the development of new
      therapeutics and diagnostic tools. We herein present the chiral pool syntheses,
      in vitro evaluation, and SAR studies of a series of d- and l-proline- as well as
      of (4R)-4-hydroxy-l-proline-derived MMP inhibitors possessing general formula 1.
      Some of the synthesized hydroxamic acids were found to be potent MMP inhibitors
      with IC50 values in the nanomolar range, also demonstrating no off-target effects
      toward the other tested Zn2+-dependent metalloproteases (ADAMs and meprins).
      Utilizing the structure of the (2S,4S)-configured 4-hydroxyproline derivative 4,
      a selective picomolar inhibitor of MMP-13, the radiolabeled counterpart [18F]4
      was successfully synthesized. The radiotracer's biodistribution in mice as well
      as its serum stability were evaluated for assessing its potential use as a MMP-13
      targeting PET imaging agent.

PMID- 27696840
TI  - Relationship of Soluble Grape-Derived Proteins to Condensed Tannin Extractability
      during Red Wine Fermentation.
AB  - In red winemaking, the extractability of condensed tannins (CT) can vary
      considerably even under identical fermentation conditions, and several
      explanations for this phenomenon have been proposed. Recent work has demonstrated
      that grape pathogenesis-related proteins (PRPs) may limit retention of CT added
      to finished wines, but their relevance to CT extractability has not been
      evaluated. In this work, Vitis vinifera and interspecific hybrids (Vitis ssp.)
      from both hot and cool climates were vinified under small-scale, controlled
      conditions. The final CT concentration in wine was well modeled from initial
      grape tannin and juice protein concentrations using the Freundlich equation (r2=
      0.686). In follow-up experiments, separation and pretreatment of juice by
      bentonite, heating, freezing, or exogenous tannin addition reduced protein
      concentrations in juices from two grape varieties. The bentonite treatment also
      led to greater wine CT for one of the varieties, indicating that prefermentation
      removal of grape protein may be a viable approach to increasing wine CT.

PMID- 27696842
TI  - Chiroptical Asymmetric Reaction Screening via Multicomponent Self-Assembly.
AB  - The self-assembly of a stereodynamic phosphine ligand, Pd(II) and a chiral amine,
      amino alcohol or amino acid gen-erates characteristic UV and CD signals that can
      be used for quantitative stereochemical analysis of the bound substrate. A robust
      mix-and-measure chiroptical sensing protocol has been developed and used for the
      determination of the abso-lute configuration, ee and yield of an amine produced
      by iridium catalyzed asymmetric hydrogenation of an iminium salt. The analysis
      requires only 1 mg of the crude reaction mixture and minimizes cost, labor, time
      and waste.

PMID- 27696843
TI  - The Bitter Chemodiversity of Hops (Humulus lupulus L.).
AB  - To map the chemodiversity of key bitter compounds in hops, a total of 75
      different samples collected from the global hop market were analyzed for 117 key
      bitter tastants by means of a multiparametric HPLC-MS/MSMRM method. Among the
      compounds detected, 2'',3''-epoxyxanthohumol was detected for the first time in
      hops and iso!xantho!humol M was identified as a marker compound for varieties
      grown in Germany. Hop ageing experiments in the absence and presence of air
      oxygen, respectively, were conducted to address the stability of hop-derived
      compounds during long-term storage.

PMID- 27696844
TI  - Control of the Chemoselectivity of Metal N-Aryl Nitrene Reactivity: C-H Bond
      Amination versus Electrocyclization.
AB  - A mechanism study to identify the elements that control the chemoselectivity of
      metal-catalyzed N-atom transfer reactions of styryl azides is presented. Our
      studies show that the proclivity of the metal N-aryl nitrene to participate in
      sp3-C-H bond amination or electrocyclization reactions can be controlled by
      either the substrate or the catalyst. Electrocyclization is favored for mono-beta
      substituted and sterically noncongested styryl azides, whereas sp3-C-H bond
      amination through an H-atom abstraction-radical recombination mechanism is
      preferred when a tertiary allylic reaction center is present. Even when a
      weakened allylic C-H bond is present, our data suggest that the indole is still
      formed through an electrocyclization instead of a common allyl radical
      intermediate. The site selectivity of metal N-aryl nitrenes was found to be
      controlled by the choice of catalyst: Ir(I)-alkene complexes trigger
      electrocyclization processes while Fe(III) porphyrin complexes catalyze sp3-C-H
      bond amination in substrates where Rh2(II) carboxylate catalysts provide both
      products.

PMID- 27696845
TI  - Conversion of Thin Stillage Compounds using Endemic Bacteria Augmented with
      Lactobacillus panis PM1B.
AB  - A consortium of organisms endemic in wheat-based thin stillage (W-TS) obtained
      from a commercial ethanol production converts glycerol to 1,3-propanediol (1,3
      PD) and lactic acid to acetic acid. We sought to improve conditions for 1,3-PD
      and acetic acid production to be used in future studies of industrial isolation
      of these compounds from two-stage fermentation. Occasionally stillage
      fermentation proceeded slowly but an inoculum of Lactobacillus panis PM1B
      augmented both fermentation rate and extent. Fermentation rate and product yield
      were enhanced by adjusting pH to 5 daily, adding glucose and glycerol (molar
      ratio 0.1:1), adding freeze-dried W-TS, and adding vitamins (B2, B3, and B12).
      1,3-PD and 3-HPA did not inhibit 1,3-PD production during fermentation. Moreover,
      agitation did not improve fermentation rate or extent. Corn sugar was a suitable
      substitute for glucose. Fermentation was performed at both 20 and 150 L, with 1,3
      PD production of 2% (w/v, 20 g/L) being routinely achieved or exceeded.

PMID- 27696846
TI  - Identification and Chemical Standardization of Licorice Raw Materials and Dietary
      Supplements Using UHPLC-MS/MS.
AB  - Defined as the roots and underground stems of principally three Glycyrrhiza
      species, G. glabra L., G.uralensis Fish. ex DC. and G. inflata Batalin, licorice
      has been used as a medicinal herb for millennia and is marketed as root sticks,
      powders and extracts. Identity tests described in most pharmacopeial monographs
      enabled the distinction of Glycyrrhiza species. Accordingly, an ultrahigh
      performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay
      using the method of standard addition was developed to quantify 14 licorice
      components (liquiritin, isoliquiritin, liquiritin apioside, isoliquiritin
      apioside, licuraside, liquiritigenin, isoliquiritigenin, glycyrrhizin,
      glycyrrhetinic acid, glabridin, glycycoumarin, licoricidin, licochalcone A, and p
      hydroxybenzylmalonic acid), representing several natural product classes
      including chalcones, flavanones, saponins, and isoflavonoids. Using this
      approach, G. glabra, G. uralensis and G. inflata in a variety of forms including
      root powders and extracts as well as complex dietary supplements could be
      differentiated and chemically standardized without concerns due to matrix
      effects.

PMID- 27696847
TI  - Study of the Vibrational Spectra and Absorption Cross Sections of 1-chloro-1
      fluoroethene by a Joint Experimental and Ab Initio Approach.
AB  - The gas-phase infrared spectra of 1-chloro-1-fluoroethene (geminal chloro
      fluoroethene, ClFC=CH2, 1,1-C2H2ClF) were recorded at medium resolution in the
      range 400 - 6400 cm-1 and the vibrational analysis led to revise the previous
      assignments for the nu11 (A'' symmetry), nu2 (A' symmetry) and nu1 (A' symmetry)
      bands. Besides the fundamentals, all the most relevant spectral features were
      interpreted in terms of overtone and combination bands, thus obtaining an
      accurate description of the vibrational structure of ClFC=CH2. Accurate
      measurements of absorption cross section spectra were carried out and integrated
      band intensity data were determined. High-level ab initio calculations of
      harmonic and anharmonic force fields thoroughly supported and guided the analysis
      and the disentangling of the several strongly coupled polyads involving many
      vibrational levels. Diagonalization of the effective Hamiltonian with the off
      diagonal elements involving several Fermi and Darling-Dennison resonance
      coefficients computed by the theoretical cubic and quartic force constants
      provided the predicted energy levels in good agreement with the vibrational
      assignments. The calculated infrared intensities, obtained by taking into account
      anharmonic corrections, were compared to the accurate experimental absorption
      cross section data here determined.

PMID- 27696848
TI  - Explicit Solvent Modeling of IR and UV-Vis Spectra of 1-Ethyl-3-methylimidazolium
      Bis(trifluoromethylsulfonyl)imide Ionic Liquid.
AB  - Explicit solvent modeling of absorption spectra of 1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide has been performed. Fourier transform of
      autocorrelation function of the dipole moment calculated from ab initio molecular
      dynamics simulations has been used to obtain the IR spectrum of the bulk liquid.
      A sequential MD/TD DFT procedure has been applied to calculate the UV-vis
      spectrum. Description of both spectra by explicit solvent model improves with
      respect to gas phase calculations or implicit solvent with good agreement between
      computed spectra and the experimental data. The major factor contributing to the
      improvement has been attributed to better description of structures of cation
      anion pairs sampled from molecular dynamics simulations. Ab initio molecular
      dynamics with Fourier transform has been demonstrated to be a powerful
      methodology to calculate bulk IR spectra of ionic liquids.

PMID- 27696849
TI  - Carbon-Coated Nickel Phosphide Nanosheets as Efficient Dual-Electrocatalyst for
      Overall Water Splitting.
AB  - Low-cost and efficient electrocatalysts for overall water splitting are in high
      demand for a wide range of applications across renewable and clean energy. Here,
      we report a simple one-step synthesis of three-dimensional (3D) carbon-coated
      Ni8P3 nanosheet array as bifunctional catalyst for both hydrogen evolution
      reactions (HER) and oxygen evolution reactions (OER). The nanosheet array
      possesses low overpotentials, high current densities and small Tafel slopes in
      both HER and OER, and shows high electrocatalytic activities and long-term
      stability. The carbon layer with high electric conductivity serves not only as a
      protective layer to prevent Ni8P3 dissolution, but also as an active layer to
      decrease the electrocatalysis overpotential. The nanosheet array has HER
      outstanding activity in both acid and alkaline media. Its superior performance in
      OER can be due to the synergistic interaction at the Ni8P3/NiOx heterojunction.
      Furthermore, cell voltage as low as 1.65 V can achieve 10 mA cm-2 current density
      for full water splitting in an alkaline water electrolyzer, indicating potential
      application of C@ Ni8P3 as bifunctional catalyst for clean and renewable energy
      utilization.

PMID- 27696851
TI  - Design of Amphiphilic Polymers via Molecular Dynamics Simulations.
AB  - Extensive all-atom molecular dynamics simulations were carried out on three novel
      amphiphilic homopolymers in explicit polar and nonpolar solvent environments.
      These nonlinear polymers have potential applications in drug delivery and
      consisted of 32 repeating bifurcated amphiphilic side chains bound to an alkynyl
      functionalized cyclic framework. All of the polymer systems investigated have the
      same backbone and hydrophobic dodecyl side chains and differ only in the nature
      of the hydrophilic side chains. This report focuses on the solvent polarity
      induced conformational changes exhibited as a result of the different hydrophilic
      modifications. Our simulations of polymer microenvironment provides useful
      information about the amphiphilic phase segregation that drives the formation of
      normal micelle-like and reverse micelle-like nanostructures that are expected to
      occur in response to solvents of varying polarities.

PMID- 27696850
TI  - Mapping the Competition between Exciton Dissociation and Charge Transport in
      Organic Solar Cells.
AB  - The competition between exciton dissociation and charge transport in organic
      solar cells comprising poly(3-hexylthiophene) [P3HT] and phenyl-C61-butyric acid
      methyl ester [PCBM] is investigated by correlated scanning confocal
      photoluminescence and photocurrent microscopies. Contrary to the general
      expectation that higher photoluminescence quenching is indicative of higher
      photocurrent, microscale mapping of bulk-heterojunction solar-cell devices shows
      that photoluminescence quenching and photocurrent can be inversely proportional
      to one another. To understand this phenomenon, we construct a model system by
      selectively laminating a PCBM layer onto a P3HT film to form a PCBM/P3HT planar
      junction on half of the device and a P3HT single junction on the other half. Upon
      thermal annealing to allow for interdiffusion of PCBM into P3HT, an inverse
      relationship between photoluminescence quenching and photocurrent is observed at
      the boundary between the PCBM/P3HT junction and P3HT layer. Incorporation of PCBM
      in P3HT works to increase photoluminescence quenching, consistent with efficient
      charge separation, but conductive atomic force microscopy measurements reveal
      that PCBM acts to decrease P3HT hole mobility, limiting the efficiency of charge
      transport. This suggests that photoluminescence-quenching measurements should be
      used with caution in evaluating new organic materials for organic solar cells.

PMID- 27696852
TI  - Multifunctional porous organic polymers: tuning of porosity, CO2 and H2 storage
      and visible-light-driven photocatalysis.
AB  - A series of porous organic polymers (POPs) were fabricated based on the boron
      dipyrromethene (BODIPY) core. The variation of the substituents in the BODIPY
      core and the fine tuning of the Sonogashira polycondenzation reaction with 1,3,5
      triethynylbenzene led to the formation of POPs with a wide range of surface area
      and porosity. A tenfold increase in surface area from 73 m2g-1 in BDT1a polymer
      to 1010 m2g-1 in BDT3 was obtained. Simultaneously, the porosity was changed from
      mesoporous to ultramicroporous. The surface area of BDT3 turned out to be the
      highest reported so far for BODIPY based POPs. Molecular dynamics simulation
      coupled with Grand Canonical Monte Carlo simulations revealed the effect of
      substituents alkyl groups and rigidity of the core structures on the surface
      properties of the POPs. Detailed gas adsorption studies of the polymers revealed
      a high uptake of CO2 and H!2. The highest uptake capacity of 16.5 wt. % for CO2
      at 273 K and 2.2 wt.% for H!2 at 77 K was observed for BDT3 at 1 bar pressure.
      Isosteric heat of adsorption (Qst) of BDT3 for CO2 was found to be as high as
      30.6 kJ mol-1. Electron paramagnetic resonance studies revealed the generation of
      singlet oxygen upon photoexcitation of these polymers. The BODIPY based POPs
      turned out to be excellent catalysts for visible-light-driven photooxidation of
      thioanisole. The present study establishes BODIPY based POPs as a new class of
      multifunctional materials.

PMID- 27696854
TI  - Optimization of Bi3+ in upconversion nanoparticles induced simultaneous
      enhancement of near-infrared optical and X-ray computed tomography imaging
      capability.
AB  - Bioimaging probes have been extensive studied for many years, while it is still a
      challenge to further improve the image quality for precise diagnosis in clinical
      medicine. Here, monodisperse NaGdF4:Yb3+,Tm3+,x% Bi3+ (abbreviated as GYT-x%
      Bi3+, x = 0, 5, 10, 15, 20, 25, 30) upconversion nanoparticles (UCNPs) have been
      prepared through solvothermal method. The near-infrared upconversion emission
      intensity of GYT-25% Bi3+ has been enhanced remarkably than that of
      NaGdF4:Yb3+,Tm3+ (GYT) with a factor of ~60. Especially, the near-infrared
      upconversion emission band centered at 802 nm is 150 times stronger than the blue
      emission band of GYT-25% Bi3+ UCNPs. Such high ratio of NIR/blue UCL intensity
      could reduce the damage to tissues in bioimaging process. The possibility of
      using GYT-25% Bi3+ UCNPs with strong near-infrared upconversion emission for
      optical imaging in vitro and in vivo was performed. Encouragingly, the UCL
      imaging penetration depth can be achieved as deep as 20 mm. Importantly, GYT-25%
      Bi3+ UCNPs exhibit a much higher X-ray computed tomography (CT) contrast
      efficiency than GYT and iodine-based contrast agent under the same clinical
      conditions, due to the high X-ray attenuation coefficient of bismuth. Hence,
      simultaneous remarkable enhancement of NIR emission and X-ray CT signal in
      upconversion nanoparticles could be achieved by optimizing the doping
      concentration of Bi3+ ions. Additionally, Gd3+ ions in the UCNPs endow GYT-25%
      Bi3+ UCNPs with T1-weighted magnetic resonance (MR) imaging capability.

PMID- 27696853
TI  - Quantitative Proteomic and Phosphoproteomic Comparison of 2D and 3D Colon Cancer
      Cell Culture Models.
AB  - Cell cultures are widely used model systems. Some immortalized cell lines can be
      grown in either two-dimensional (2D) adherent monolayers or in three-dimensional
      (3D) multicellular aggregates, or spheroids. Here, the quantitative proteome and
      phosphoproteome of colon carcinoma HT29 cells cultures in 2D monolayers and 3D
      spheroids were compared with a stable isotope labeling of amino acids (SILAC)
      labeling strategy. Two biological replicates from each sample were examined, and
      notable differences in both the proteome and the phosphoproteome were determined
      by nanoliquid chromatography tandem mass spectrometry (LC-MS/MS) to assess how
      growth configuration affects molecular expression. A total of 5867 protein
      groups, including 2523 phosphoprotein groups and 8733 phosphopeptides were
      identified in the samples. The Gene Ontology analysis revealed enriched GO terms
      in the 3D samples for RNA binding, nucleic acid binding, enzyme binding,
      cytoskeletal protein binding, and histone binding for their molecular functions
      (MF) and in the process of cell cycle, cytoskeleton organization, and DNA
      metabolic process for the biological process (BP). The KEGG pathway analysis
      indicated that 3D cultures are enriched for oxidative phosphorylation pathways,
      metabolic pathways, peroxisome pathways, and biosynthesis of amino acids. In
      contrast, analysis of the phosphoproteomes indicated that 3D cultures have
      decreased phosphorylation correlating with slower growth rates and lower cell-to
      extracellular matrix interactions. In sum, these results provide quantitative
      assessments of the effects on the proteome and phosphoproteome of culturing cells
      in 2D versus 3D cell culture configurations.

PMID- 27696856
TI  - UV-Induced Oxygen Removal for Photostable, High-Efficiency PTB7-Th:PC71BM
      Photovoltaic Cells.
AB  - Solution-processed ZnO sol-gel or nanoparticles are widely used as the electron
      transporting layer (ETL) in optoelectronic devices. However, chemisorbed oxygen
      on the ZnO layer surface has been shown to be detrimental for the device
      performance as well as stability. Herein, we demonstrate that chemisorbed oxygen
      removal based on UV illumination of the ZnO surface layer under a nitrogen
      atmosphere can, simultaneously, improve the power conversion efficiency and
      photostability of PTB7-Th:PC71BM-based inverted polymer solar cells. By a
      systematic study of such a UV illumination procedure, we obtained optimal
      conditions where both the cell efficiency and stability were improved. We
      fabricated cells with a power conversion efficiency higher than 9.8% and with a
      T80 lifetime longer than 500 h, corresponding to about a 2.5-fold enhancement
      relative to non-UV-treated ZnO reference devices.

PMID- 27696857
TI  - Noninvasive Ablation of Prostate Cancer Spheroids Using Acoustically-Activated
      Nanodroplets.
AB  - We have developed acoustically activated nanodroplets (NDs) using an amphiphilic
      triblock copolymer, which self-assembles and encapsulates different
      perfluorocarbons including perfluoropentane (PFP) and perfluorohexane (PFH).
      Applying histotripsy pulses (i.e., short, high pressure, ultrasound pulses) to
      solutions of PFP- and PFH-NDs generated bubble clouds at a significantly reduced
      acoustic pressure compared to the cavitation pressure observed for histotripsy
      treatment alone. In this report, we summarize the results of combining
      histotripsy at low frequency (345 and 500 kHz) with PFP-NDs and PFH-NDs on the
      ablation of PC-3 and C4-2B prostate cancer cells. Using custom built histotripsy
      transducers coupled to a microscope and a high speed recording camera, we imaged
      the generation of a cavitation bubble cloud in response to different ultrasound
      regimes in solution and in tissue-mimicking gel phantoms. We quantified the
      associated ablation of individual cancer cells and 3D spheroids suspended in
      solution and embedded in tissue phantoms to compare the ablative capacity of PFP
      NDs and PFH-NDs. Results show that histotripsy pulses at high acoustic pressure
      (26.2 MPa) ablated 80% of prostate cancer spheroids embedded in tissue-mimicking
      gel phantoms. In comparison, combining histotripsy pulses at a dramatically lower
      acoustic pressure (12.8 MPa) with PFP-NDs and PFH-NDs caused an ablation of 40%
      and 80% of the tumor spheroid volumes, respectively. These results show the
      potential of acoustically activated NDs as an image-guided ablative therapy for
      solid tumors and highlight the higher ablative capacity of PFH-NDs, which
      correlates with the boiling point of the encapsulated PFH and the stability of
      the formed bubble cloud.

PMID- 27696860
TI  - Response to Comment on "Impact to Underground Sources of Drinking Water and
      Domestic Wells from Production Well Stimulation and Completion Practices in the
      Pavillion, Wyoming Field".

PMID- 27696858
TI  - Improving Efficacy, Oral Bioavailability, and Delivery of Paclitaxel Using
      Protein-Grafted Solid Lipid Nanoparticles.
AB  - Oral delivery of anticancer drugs remains challenging despite the most convenient
      route of drug administration. Hydrophobicity and nonspecific toxicities of
      anticancer agents are major impediments in the development of oral formulation.
      In this study, we developed wheat germ agglutinin (WGA)-conjugated, solid lipid
      nanoparticles to improve the oral delivery of the hydrophobic anticancer drug,
      paclitaxel (PTX). This study was focused to improve the PTX loading in
      biocompatible lipid matrix with high bioconjugation efficiency. WGA-conjugated,
      PTX-loaded solid lipid nanoparticles (LPSN) exhibited enhanced anticancer
      activity against A549 lung cancer cells after internalization through lectin
      receptors than free PTX. Biodistribution studies in rats revealed that LPSN
      significantly improved the oral bioavailability and lung targetability of PTX,
      which could be due to cumulative bioadhesive property of the nanocarrier system
      and the targeting ligand WGA.

PMID- 27696859
TI  - Vacancy-Induced Semiconductor-Insulator-Metal Transitions in Nonstoichiometric
      Nickel and Tungsten Oxides.
AB  - Metal-insulator transitions in strongly correlated oxides induced by
      electrochemical charging have been attributed to formation of vacancy defects.
      However, the role of native defects in affecting these transitions is not clear.
      Here, we report a new type of phase transition in p-type, nonstoichiometric
      nickel oxide involving a semiconductor-to-insulator-to-metal transition along
      with the complete reversal of conductivity from p- to n-type at room temperature
      induced by electrochemical charging in a Li+-containing electrolyte. Direct
      observation of vacancy-ion interactions using in situ near-infrared
      photoluminescence spectroscopy show that the transition is a result of
      passivation of native nickel (cationic) vacancy defects and subsequent formation
      of oxygen (anionic) vacancy defects driven by Li+ insertion into the lattice.
      Changes in the oxidation states of nickel due to defect interactions probed by X
      ray photoemission spectroscopy support the above conclusions. In contrast, n
      type, nonstoichiometric tungsten oxide shows only insulator-to-metal transition,
      which is a result of oxygen vacancy formation. The defect-property correlations
      shown here in these model systems can be extended to other oxides.

PMID- 27696861
TI  - Comment on "Impact to Underground Sources of Drinking Water and Domestic Wells
      from Production Well Stimulation and Completion Practices in the Pavillion,
      Wyoming, Field".

PMID- 27696862
TI  - Pathway-Based Approaches for Environmental Monitoring and Risk Assessment.

PMID- 27696855
TI  - Determining the Mitochondrial Methyl Proteome in Saccharomyces cerevisiae using
      Heavy Methyl SILAC.
AB  - Methylation is a common and abundant post-translational modification. High
      throughput proteomic investigations have reported many methylation sites from
      complex mixtures of proteins. The lack of consistency between parallel studies,
      resulting from both false positives and missed identifications, suggests problems
      with both over-reporting and under-reporting methylation sites. However, isotope
      labeling can be used effectively to address the issue of false-positives, and
      fractionation of proteins can increase the probability of identifying methylation
      sites in lower abundance. Here we have adapted heavy methyl SILAC to analyze
      fractions of the budding yeast Saccharomyces cerevisiae under respiratory
      conditions to allow for the production of mitochondria, an organelle whose
      proteins are often overlooked in larger methyl proteome studies. We have found 12
      methylation sites on 11 mitochondrial proteins as well as an additional 14
      methylation sites on 9 proteins that are nonmitochondrial. Of these methylation
      sites, 20 sites have not been previously reported. This study represents the
      first characterization of the yeast mitochondrial methyl proteome and the second
      proteomic investigation of global mitochondrial methylation to date in any
      organism.

PMID- 27696865
TI  - Electrochemical Synthesis of Highly Oriented, Transparent, and Pinhole-Free ZnO
      and Al-Doped ZnO Films and Their Use in Heterojunction Solar Cells.
AB  - Electrochemical synthesis conditions using nonaqueous solutions were developed to
      prepare highly transparent (T > 90%) and crystalline ZnO and Al-doped ZnO (AZO)
      films for use in solar energy conversion devices. A focused effort was made to
      produce pinhole-free films in a reproducible manner by identifying a key
      condition to prevent the formation of cracks during deposition. The
      polycrystalline domains in the resulting films had a uniform orientation (i.e.,
      the c-axis perpendicular to the substrate), which enhanced the electron transport
      properties of the films. Furthermore, electrochemical Al doping of ZnO using
      nonaqueous media, which was demonstrated for the first time in this study,
      effectively increased the carrier density and raised the Fermi level of ZnO.
      These films were coupled with an electrodeposited p-type Cu2O to construct p-n
      heterojunction solar cells to demonstrate the utilization of these films for
      solar energy conversion. The resulting n-ZnO/p-Cu2O and n-AZO/p-Cu2O cells showed
      excellent performance compared with previously reported n-ZnO/p-Cu2O cells
      prepared by electrodeposition. In particular, replacing ZnO with AZO resulted in
      simultaneous enhancements in short circuit current and open circuit potential,
      and the n-AZO/p-Cu2O cell achieved an average power conversion efficiency (eta)
      of 0.92 +/- 0.09%. The electrodeposition condition reported here will offer a
      practical and versatile way to produce ZnO or AZO films, which play key roles in
      various solar energy conversion devices, with qualities comparable to those
      prepared by vacuum-based techniques.

PMID- 27696864
TI  - Probing Grain-Boundary Chemistry and Electronic Structure in Proton-Conducting
      Oxides by Atom Probe Tomography.
AB  - A laser-assisted atom-probe-tomographic (LAAPT) method has been developed and
      applied to measure and characterize the three-dimensional atomic and electronic
      nanostructure at an yttrium-doped barium zirconate (BaZr0.9Y0.1O3-delta, BZY10)
      grain boundary. Proton-conducting perovskites, such as BZY10, are attracting
      intense interest for a variety of energy conversion applications. However, their
      implementation has been hindered, in part, because of high grain-boundary (GB)
      resistance that is attributed to a positive GB space-charge layer (SCL). In this
      study, LAAPT is used to analyze BZY10 GB chemistry in three dimensions with
      subnanometer resolution. From this analysis, maps of the charge density and
      electrostatic potential arising at the GBs are derived, revealing for the first
      time direct chemical evidence that a positive SCL indeed exists at these GBs.
      These maps reveal new insights on the inhomogeneity of the SCL region and produce
      an average GB potential barrier of approximately 580 mV, agreeing with previous
      indirect electrochemical measurements.

PMID- 27696863
TI  - 64Cu-Labeled Gp2 Domain for PET Imaging of Epidermal Growth Factor Receptor.
AB  - This purpose of this study is to determine the efficacy of a 45-amino acid Gp2
      domain, engineered to bind to epidermal growth factor receptor (EGFR), as a
      positron emission tomography (PET) probe of EGFR in a xenograft mouse model. The
      EGFR-targeted Gp2 (Gp2-EGFR) and a nonbinding control were site-specifically
      labeled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)
      chelator. Binding affinity was tested toward human EGFR and mouse EGFR.
      Biological activity on downstream EGFR signaling was examined in cell culture.
      DOTA-Gp2 molecules were labeled with 64Cu and intravenously injected (0.6-2.3
      MBq) into mice bearing EGFRhigh (n = 7) and EGFRlow (n = 4) xenografted tumors.
      PET/computed tomography (CT) images were acquired at 45 min, 2 h, and 24 h.
      Dynamic PET (25 min) was also acquired. Tomography results were verified with
      gamma counting of resected tissues. Two-tailed t tests with unequal variances
      provided statistical comparison. DOTA-Gp2-EGFR bound strongly to human (KD = 7 +/
      5 nM) and murine (KD = 29 +/- 6 nM) EGFR, and nontargeted Gp2 had no detectable
      binding. Gp2-EGFR did not agonize EGFR nor antagonize EGF-EGFR. 64Cu-Gp2-EGFR
      tracer effectively localized to EGFRhigh tumors at 45 min (3.2 +/- 0.5%ID/g).
      High specificity was observed with significantly lower uptake in EGFRlow tumors
      (0.9 +/- 0.3%ID/g, p < 0.001), high tumor-to-background ratios (11 +/- 6
      tumor/muscle, p < 0.001). Nontargeted Gp2 tracer had low uptake in EGFRhigh
      tumors (0.5 +/- 0.3%ID/g, p < 0.001). Similar data was observed at 2 h, and tumor
      signal was retained at 24 h (2.9 +/- 0.3%ID/g). An engineered Gp2 PET imaging
      probe exhibited low background and target-specific EGFRhigh tumor uptake at 45
      min, with tumor signal retained at 24 h postinjection, and compared favorably
      with published EGFR PET probes for alternative protein scaffolds. These
      beneficial in vivo characteristics, combined with thermal stability, efficient
      evolution, and small size of the Gp2 domain validate its use as a future class of
      molecular imaging agents.

PMID- 27696866
TI  - HSP47 Promotes Glioblastoma Stemlike Cell Survival by Modulating Tumor
      Microenvironment Extracellular Matrix through TGF-beta Pathway.
AB  - Grade IV glioblastoma multiforme (GBM) is the most malignant form of gliomas.
      HSP47, encoded by SERPINH1 gene, is a serpin which serves as a human chaperone
      protein for collagen. We have shown that HSP47 is significantly overexpressed in
      GBM and associated with tumor grade. However, the role of HSP47 on GBM
      progression and stemlike property remains unclear. The stable overexpression of
      HSP47 in primary GBM cells was established by lentivirus infection. The effects
      of HSP47 overexpression on tumor growth and the effects of blocking the TGF-beta
      pathway on tumor regression were investigated by animal study. The expression of
      HSP47 was examined by real time qRT-PCR and immunohistochemistry. The stemlike
      property was investigated by sphere formation and CD44 cell population analysis
      using flow cytometry. We found that overexpression of HSP47 promotes primary
      glioma cell tumor formation, invasion, angiogenesis, and stemlike properties. The
      overexpression of HSP47 was correlated and promoted extracellular matrix (ECM)
      related genes through the TGF-beta pathway in GBM. Blocking TGF-beta pathway
      overcomes HSP47 induced tumorigenesis and stemness. This study demonstrated that
      HSP47 promotes GBM stemlike cell survival by modulating tumor microenvironment
      ECM through TGF-beta pathway. Blocking the TGF-beta pathway provides a promising
      therapeutic potential for HSP47 overexpressed GBM.

PMID- 27696868
TI  - Effect of Final Monomer Deposition Steps on Molecular Layer-by-Layer Polyamide
      Surface Properties.
AB  - A current challenge to desalination membrane technology is the inability to
      precisely control the properties of the polyamide selective layer due to the
      complexity of interfacial polymerization. In this study, we investigate the
      ability of molecular layer-by-layer (mLbL) assembly, an alternative polyamide
      fabrication technique, to create polyamide surfaces with tunable chemistry. We
      explore the influence of terminating monomer, monomer deposition time, monomer
      size, and the presence of underlying ionizable functional groups on mLbL-derived
      polyamide surface properties. AFM colloidal probe measurements, contact angle
      titrations, QCM cesium adsorption experiments, and XPS data show that polyamide
      films terminated with m-phenylene diamine (MPD) or trimesoyl chloride (TMC) for
      20-30 seconds are chemically similar. Increasing terminating monomer deposition
      time or using a smaller, more reactive monomer results in more distinct colloidal
      probe adhesive interactions, contact angle titration curves, negative charge
      densities, and near surface atomic compositions. By optimizing the final monomer
      deposition steps, both amine-rich and carboxyl-rich polyamide surfaces can be
      fabricated, which has implications for the application of mLbL assembly to
      membrane-based desalination.

PMID- 27696867
TI  - Fecal Metabolome in Hmga1 Transgenic Mice with Polyposis: Evidence for Potential
      Screen for Early Detection of Precursor Lesions in Colorectal Cancer.
AB  - Because colorectal cancer (CRC) remains a leading cause of cancer mortality
      worldwide, more accessible screening tests are urgently needed to identify early
      stage lesions. We hypothesized that highly sensitive, metabolic profile analysis
      of stool samples will identify metabolites associated with early stage lesions
      and could serve as a noninvasive screening test. We therefore applied traveling
      wave ion mobility mass spectrometry (TWIMMS) coupled with ultraperformance liquid
      chromatography (UPLC) to investigate metabolic aberrations in stool samples in a
      transgenic model of premalignant polyposis aberrantly expressing the gene
      encoding the high mobility group A (Hmga1) chromatin remodeling protein. Here, we
      report for the first time that the fecal metabolome of Hmga1 mice is distinct
      from that of control mice and includes metabolites previously identified in human
      CRC. Significant alterations were observed in fatty acid metabolites and
      metabolites associated with bile acids (hypoxanthine xanthine, taurine) in Hmga1
      mice compared to controls. Surprisingly, a marked increase in the levels of
      distinctive short, arginine-enriched, tetra-peptide fragments was observed in the
      transgenic mice. Together these findings suggest that specific metabolites are
      associated with Hmga1-induced polyposis and abnormal proliferation in intestinal
      epithelium. Although further studies are needed, these data provide a compelling
      rationale to develop fecal metabolomic analysis as a noninvasive screening tool
      to detect early precursor lesions to CRC in humans.

PMID- 27696869
TI  - A Route to Polysubstituted Aziridines from Carbenes and Imines through a Nondiazo
      Approach.
AB  - An efficient method for the synthesis of polysubstituted aziridines utilizing
      enynones and imines is described. This transformation is achieved through the
      reaction of imines with donor/donor carbene intermediates, which were generated
      in situ from the cyclization of enynones. Furthermore, the resulted aziridines
      were good 1,3-dipoles, which could be efficiently trapped by dipolarophiles to
      give five-membered heterocycles. The obvious advantages of wide substrate scopes,
      mild reaction conditions, and high atom efficiency make this system highly
      appealing for construction of polysubstituted aziridines, 2,5-dihydropyroles, and
      1,2,4-triazolidines.

PMID- 27696870
TI  - Ostwald ripening growth mechanism of gold nanotriangles in vesicular template
      phases.
AB  - The mechanism of nanotriangle formation in multivesicular vesicles (MMV) is
      investigated by using time dependent SAXS measurements in combination with UV-vis
      spectroscopy, light and transmission electron microscopy. In the first time
      period 6.5 nm sized spherical gold nanoparticles are formed inside of the
      vesicles, which build up soft nanoparticle aggregates. In situ SAXS experiments
      show a linear increase of the volume and molar mass of nanotriangles in the
      second time period. The volume growth rate of the triangles is 16.1 nm3/min and
      the growth rate in vertical direction only 0.02 nm/min. Therefore, flat
      nanotriangles with a thickness of 7 nm and diameters of 23 nm are formed. This
      process can be described by a diffusion-limited Ostwald ripening growth
      mechanism. TEM micrographs visualize soft coral-like structures with thin
      nanoplatelets at the periphery of the aggregates, which disaggregate in the third
      time period into nanotriangles and spherical particles. The 16 times faster
      growth of nanotriangles in lateral than that in vertical direction is related to
      the adsorption of symmetry breaking components, i.e., AOT and the polyampholyte
      PalPhBisCarb, on the {111} facets of the gold nanoplatelets in combination with
      confinement effects of the vesicular template phase.

PMID- 27696871
TI  - Stereoselective Radical Cyclization Cascades Triggered by Addition of Diverse
      Radicals to Alkynes To Construct 6(5)-6-5 Fused Rings.
AB  - Cascade radical cyclization of alkynyl ketones with various carbon- and
      heteroatom-centered radical precursors via a sequential radical addition/1,5-H
      radical shift/5-exo-trig/radical cyclization process was realized for the first
      time. This method provides a strategically novel and step-economical protocol for
      diversity-oriented synthesis of a wide range of carbocyclic and heterocyclic 6(5)
      6-5 fused ring systems with three contiguous stereocenters, including a
      quaternary carbon in high yields with excellent chemo- and diastereoselectivity.

PMID- 27696872
TI  - Structurally Simple Benzylidene-Type Photolabile Diol Protecting Groups.
AB  - Two structurally simple photolabile protecting groups for releasing 1,2- and 1,3
      diols have been developed. The diols can be protected in high yields and released
      from their corresponding acetals with high chemical efficiency.

PMID- 27696873
TI  - Mechanistic Study on Pd/Mono-N-protected Amino Acid Catalyzed Vinyl-Vinyl
      Coupling Reactions: Reactivity and E/Z Selectivity.
AB  - A combined mass spectrometric and computational study of the Pd/mono-N-protected
      amino acid (MPAA)-catalyzed vinyl-vinyl coupling reactions is reported.
      Computational study reveals that the reaction is initiated by C-H activation of
      the styrene followed by the insertion of acrylate. This is supported by mass
      spectrometry. The MPAA ligand facilitates the cross-coupling reaction between
      monosubstituted alkenes by stabilizing the active palladium catalyst and offering
      the N-protecting group as a stronger base than acetate. The E/Z selectivity is
      attributed to the stronger d-pi interaction between the catalyst and the
      substrate in the transition state leading to E product.

PMID- 27696874
TI  - Doped Organic Transistors.
AB  - Organic field-effect transistors hold the promise of enabling low-cost and
      flexible electronics. Following its success in organic optoelectronics, the
      organic doping technology is also used increasingly in organic field-effect
      transistors. Doping not only increases device performance, but it also provides a
      way to fine-control the transistor behavior, to develop new transistor concepts,
      and even improve the stability of organic transistors. This Review summarizes the
      latest progress made in the understanding of the doping technology and its
      application to organic transistors. It presents the most successful doping models
      and an overview of the wide variety of materials used as dopants. Further, the
      influence of doping on charge transport in the most relevant polycrystalline
      organic semiconductors is reviewed, and a concise overview on the influence of
      doping on transistor behavior and performance is given. In particular, recent
      progress in the understanding of contact doping and channel doping is summarized.

PMID- 27696876
TI  - Virtual Issue in Memory of Ahmed Zewail.

PMID- 27696877
TI  - Engineering an ABC transporter for enhancing resistance to caffeine in
      Saccharomyces cerevisiae.
AB  - In addressing caffeine toxicity to the producing cells, engineering a transporter
      that can move caffeine from cytoplasm across cell membrane to extracellular
      space, thus enhancing caffeine resistance and potentially increasing the yield in
      yeast are important. An ABC-transporter bfr1 from Schizosaccharomyces pombe was
      cloned and transformed into S. cerevisiae, resulting in enhancing caffeine
      resistance. Afterwards, a library of randomly mutagenized bfr1 mutants through
      error-prone PCR was generated. It was identified one mutant with drastically
      increased caffeine resistance (15 mg/mL). Sequencing and structural analysis
      illustrated that many of the mutations occurred at the cytosolic domain. Site
      directed mutagenesis of these mutations confirmed at least one amino acid that
      conferred enhancing caffeine resistance in the mutated bfr1. These data
      demonstrated engineering ABC-transporters can be an efficient way to reduce
      product toxicity in heterologous systems.

PMID- 27696875
TI  - Unravelling the Binding Mechanism of a Poly(cationic) Anthracenyl Fluorescent
      Probe with High Affinity toward Double-Stranded DNA.
AB  - We report the synthesis, spectroscopy, and the DNA binding properties of a
      biocompatible, water-soluble, polycationic two-photon absorbing anthracenyl
      derivative (Ant-PIm) specifically designed for biorelated applications. Detailed
      insights into the Ant-PIm-DNA binding interaction are provided by using several
      spectroscopic approaches, including UV-vis absorption, circular dichroism (CD),
      Fourier-transform infrared spectroscopy (FTIR), steady-state, and time-resolved
      fluorescence techniques. Absorption and fluorescence quantitative data analysis
      show a strong Ant-PIm-duplex interaction with binding constants of Kf = 4.7 +/-
      0.2 * 105 M-1, 7.1 +/- 0.3 * 105 M-1, and 1.0 +/- 0.1 * 106 M-1 at 298, 304, and
      310 K, respectively. Spectral changes observed upon DNA binding provide evidence
      for a complex formation with off-on fluorescence pattern, which can be related to
      two consecutive binding equilibria. Results of DNA binders displacement and
      iodide quenching experimental assays unambiguously point to the groove binding
      mode of Ant-PIm to the DNA-helicate. Thermodynamic and chemical denaturation
      studies suggest that long-range interactions of hydrophobic nature regulate the
      association of Ant-PIm with the biopolymer. The ionic strength dependence of the
      binding constant shows that electrostatic component has an important contribution
      to the overall Gibbs free energy. FTIR and CD data provide evidence of partial
      modification of the B-DNA secondary structure, while the increase in the melting
      temperature clearly indicates the enhancement of the thermal stability of the
      duplex. Furthermore, the two-photon absorption cross section spectrum determined
      using the two-photon excited fluorescence (TPEF) technique shows a strong 2PA
      maximum at 820 nm with a sigma2 > 800 GM, which emphasizes the advantageous
      combination of biological and optical properties possessed by this positively
      charged bioprobe.

PMID- 27696878
TI  - Polyanils and Polyboranils: Synthesis, Optical Properties, and Aggregation
      Induced Emission.
AB  - A first series of polyanils were synthesized by a simple condensation between
      either isomers of phenylenediamine derivatives or 1,3,5-benzenetriamine and 4
      (diethylamino)salicylaldehyde, while a second series resulted from the
      condensation between 4,6-dihydroxyisophthalaldehyde or 2,5
      dihydroxyterephthalaldehyde and differently substituted anilines. All these
      polyanils showed good chelating abilities toward trivalent boron fragments such
      as BF2 or BPh2 to yield the corresponding boranils. The optical properties of
      these novel fluorophores have been studied both in solution and in the solid
      state and show emission wavelengths covering the entire visible spectrum and near
      infrared (NIR), depending on molecular structure, substitution, and environment.
      While faintly fluorescent in solution in their molecular state, some polyanils
      show typical aggregation-induced emission (AIE) behavior upon addition of
      increasing amounts of water in THF solution, leading to a sizable enhancement of
      fluorescence intensity.

PMID- 27696879
TI  - FeCl3-Catalyzed Cross-Dehydrogenative Coupling between Imidazoheterocycles and
      Oxoaldehydes.
AB  - An Fe(III)-catalyzed efficient dicarbonylation of imidazoheterocycles has been
      developed through cross-dehydrogenative coupling between imidazoheterocycles and
      oxoaldehydes under ambient air in high yields. The present protocol is also
      applicable to indolizines. Imidazopyridine produced bisimidazopyridine with
      arylaldehyde. Experimental results suggest that the reactions proceed through the
      nonradical pathway.

PMID- 27696880
TI  - Design, Synthesis, and Evaluation of Diazeniumdiolate-Based DNA Cross-Linking
      Agents Activatable by Glutathione S-Transferase.
AB  - A novel class of O2-(2,4-dinitrophenyl)-1-[N,N-bis(2-substituted
      ethyl)amino]diazen-1-ium-1,2-diolates 4-6 were designed, synthesized, and
      biologically evaluated. The most active compound 6 caused significant DNA damage
      by releasing N,N-bis(2-TsO ethyl)amine and two molecules of nitric oxide (NO)
      after activation by GST/GSH in cancer cells, being more cytotoxic against three
      cancer cell lines than a well-known diazeniumdiolate-based anticancer agent JS-K,
      suggesting that the strategy has potential to extend to other O2-derived
      diazeniumdiolates to improve anticancer activity.

PMID- 27696881
TI  - Quantitative Secretome Analysis of Activated Jurkat Cells Using Click Chemistry
      Based Enrichment of Secreted Glycoproteins.
AB  - Quantitative secretome analyses are a high-performance tool for the discovery of
      physiological and pathophysiological changes in cellular processes. However,
      serum supplements in cell culture media limit secretome analyses, but serum
      depletion often leads to cell starvation and consequently biased results. To
      overcome these limiting factors, we investigated a model of T cell activation
      (Jurkat cells) and performed an approach for the selective enrichment of secreted
      proteins from conditioned medium utilizing metabolic marking of newly synthesized
      glycoproteins. Marked glycoproteins were labeled via bioorthogonal click
      chemistry and isolated by affinity purification. We assessed two labeling
      compounds conjugated with either biotin or desthiobiotin and the respective
      secretome fractions. 356 proteins were quantified using the biotin probe and 463
      using desthiobiotin. 59 proteins were found differentially abundant (adjusted p
      value <=0.05, absolute fold change >=1.5) between inactive and activated T cells
      using the biotin method and 86 using the desthiobiotin approach, with 31 mutual
      proteins cross-verified by independent experiments. Moreover, we analyzed the
      cellular proteome of the same model to demonstrate the benefit of secretome
      analyses and provide comprehensive data sets of both. 336 proteins (61.3%) were
      quantified exclusively in the secretome. Data are available via ProteomeXchange
      with identifier PXD004280.

PMID- 27696882
TI  - Hot Carrier Extraction from Multilayer Graphene.
AB  - Hot carriers in semiconductor or metal nanostructures are relevant, for instance,
      to enhance the activity of oxide-supported metal catalysts or to achieve
      efficient photodetection using ultrathin semiconductor layers. Moreover, rapid
      collection of photoexcited hot carriers can improve the efficiency of solar
      cells, with a theoretical maximum of 85%. Because of the long lifetime of
      secondary excited electrons, graphene is an especially promising two-dimensional
      material to harness hot carriers for solar-to-electricity conversion. However,
      the photoresponse of thus far realized graphene photoelectric devices is mainly
      governed by thermal effects, which yield only a very small photovoltage. Here, we
      report a Gr-TiOx-Ti heterostructure wherein the photovoltaic effect is
      predominant. By doping the graphene, the open circuit voltage reaches values up
      to 0.30 V, 2 orders of magnitude larger than for devices relying upon the
      thermoelectric effect. The photocurrent turned out to be limited by trap states
      in the few-nanometer-thick TiOx layer. Our findings represent a first valuable
      step toward the integration of graphene into third-generation solar cells based
      upon hot carrier extraction.

PMID- 27696883
TI  - Ambient-Air Stable Lithiated Anode for Rechargeable Li-Ion Batteries with High
      Energy Density.
AB  - An important requirement of battery anodes is the processing step involving the
      formation of the solid electrolyte interphase (SEI) in the initial cycle, which
      consumes a significant portion of active lithium ions. This step is more critical
      in nanostructured anodes with high specific capacity, such as Si and Sn, due to
      their high surface area and large volume change. Prelithiation presents a viable
      approach to address such loss. However, the stability of prelithiation reagents
      is a big issue due to their low potential and high chemical reactivity toward O2
      and moisture. Very limited amount of prelithiation agents survive in ambient air.
      In this research, we describe the development of a trilayer structure of active
      material/polymer/lithium anode, which is stable in ambient air (10-30% relative
      humidity) for a period that is sufficient to manufacture anode materials. The
      polymer layer protects lithium against O2 and moisture, and it is stable in
      coating active materials. The polymer layer is gradually dissolved in the battery
      electrolyte, and active materials contact with lithium to form lithiated anode.
      This trilayer-structure not only renders electrodes stable in ambient air but
      also leads to uniform lithiation. Moreover, the degree of prelithiation could
      vary from compensating SEI to fully lithiated anode. With this strategy, we have
      achieved high initial Coulombic efficiency of 99.7% in graphite anodes, and over
      100% in silicon nanoparticles anodes. The cycling performance of lithiated anodes
      is comparable or better than those not lithiated. We also demonstrate a
      Li4Ti5O12/lithiated graphite cell with stable cycling performance. The trilayer
      structure represents a new prelithiation method to enhance performance of Li-ion
      batteries.

PMID- 27696884
TI  - Inherent vs Apparent Chemoselectivity in the Kumada-Corriu Cross-Coupling
      Reaction.
AB  - The Kumada-Corriu reaction is a powerful tool for C-C bond formation, but is
      seldom utilized due to perceived chemoselectivity issues. Herein, we demonstrate
      that high-yielding couplings can occur in the presence of many electrophilic and
      heterocyclic functional groups. Our strategy is mechanically based, matching
      oxidative addition rates with the rate of syringe pump addition of the Grignard
      reagent. The mechanistic reason for the effectiveness of this strategy is
      uncovered by continuous-infusion ESI-MS studies.

PMID- 27696885
TI  - [Health literacy in Czech population results of the comparative representative
      research].
AB  - Health literacy survey was carried out at the end of 2014 in the context of
      preparation of implementation strategy of the Program Health 2020 in the Czech
      Republic. The survey was conducted by the National Institute of Public Health
      with financial support from the Ministry of Health and the Czech WHO office.
      Sociological survey replicated comparative research conducted in eight EU
      countries in the first half of this decade. Representative survey in 1037
      respondents in the age over 16 years, selected in all regions of the country. The
      identical methodology as used in the original study was utilized. Health literacy
      was measured in the areas of health care, disease prevention and health
      promotion.We found that 59,4 % of respondents showed limited general health
      literacy; health literacy in health care is proved to be 49.5 % of the
      population, in the area of disease prevention it was 54.1 % respondents and in
      health promotion it was even even 64.3 % of respondents. Compared to the other
      countries surveyed, Czech Republic occupies the eighth, penultimate place. Health
      literacy is correlated negatively with age and positively with education. We
      found a strong social gradient of health literacy which rises with social status.
      Health literacy quite significantly influences the health status and health
      behaviors.Key words: health literacy, health behaviour, health promotion, social
      determinants of health.

PMID- 27696886
TI  - [International Comparison of Health System Performance in Visegrad Countries].
AB  - The objective of this study is to evaluate performance of the health systems in
      Visegrad countries - the Czech Republic, Hungary, Poland, and Slovakia. For a
      comparison, Austria and Germany are included, as they represent Western European
      countries neighbouring with the Visegrad countries. The health system performance
      is evaluated by six different measures.In spite of the fact, that methodologies,
      sets of countries, and time periods differ, we observe very similar findings. The
      Czech Republic has the best performing health system from the Visegrad countries,
      and Hungary looks like having the worst performing health system. In case of
      Poland, the indicators based on subjective view of population show worse
      performance of the health system than the other more objectively oriented
      indicators. It seems that Polish people view the health system too negatively in
      comparison with its real performance. If Germany and Austria are included in the
      comparison, we observe an existing gap between these two Western European
      countries and Visegrad countries.Key words: health system performance, Visegrad
      countries, international comparison.

PMID- 27696887
TI  - [Social medicine, public health and governance for health].
AB  - Social medicine, public health and governance for health have a long tradition in
      the Czech Republic but some problems persist. Possible solutions are reliable
      information, research, education and training. Action plans for Health 2020
      implementation are appreciated as well as a valuable help of the WHO Country
      Office, Czech Republic.Key words: social medicine, public health, health, health
      governance, governance for health, Health 2020, World Health Organization.

PMID- 27696888
TI  - [Alternative healing methods around us].
AB  - This article gives information on selected alternative medicine methods (AMM)
      under conditions of the Czech health care system. They can be defined as
      contemporaneous diagnostic and therapeutic methods which differ in their
      theoretical fundaments as well as practices from the evidence based medicine.
      This definition is controversial because these methods are an intrinsically
      incompatible aggregate of modalities acting as a placebo above all. We can
      encounter many "therapeutic" and "examination" methods which are practiced namely
      by healers without formal medical education, and connected closely with
      esotericism. A general feature of the alternative methods is a void usage of
      scientific concepts and theories, e.g. the concept of energy.Motivations of
      patients and doctors are briefly introduced here. However, AMM is also an ethical
      problem because the doctor should help the patient with maximum efficiency hence
      excluding the methods with a questionable, small or negligible efficiency. The
      opinions how to find the way out from this situation are divergent. It could be a
      refusal or a very reserved attitude to AMM plus maximisation of the placebo
      effect enhancing the efficiency of a rational therapy. Furthermore, the methods
      most spread in the Czech Republic are subjected to elementary critics - the
      homoeopathy, acupuncture, the so-called "bioresonance" instrumental methods,
      psychic healing, and also some refused methods in cancer treatment. In our
      opinion medicine disposes of sufficient knowledge and experience to assess the
      efficiency of AMM and refuse them in causal therapy, eventually. Their use as a
      placebo should be carefully considered.Key words: alternative medicine, placebo,
      homeopathy, acupuncture.

PMID- 27696889
TI  - [Cross-border healthcare in European Union and Czech Republic].
AB  - Currently, the cross-border healthcare still represents a marginal part of the
      Czech healthcare system's performance, though. Compared to the total healthcare
      expenditures in the Czech Republic that accounted for CZK 299.9 billion in 2014,
      the costs of the treatment provided to Czech patients abroad constitute mere
      0.27%, and the (subsequently refunded) costs of the treatment provided to foreign
      patients in the Czech Republic 0.24%.Although data on changes in the volume and
      reimbursements of healthcare due to the Directive 2011/24/EU have not been
      published yet, we can expect rather evolutionary than revolutionary development
      of cross-border healthcare volumes. Taking into account all available data, we
      can conclude that the cross-border healthcare, as specified by the directive
      currently in force, is important in our conditions above all in relation to our
      neighbours, i. e. Germany, Austria, Slovakia and Poland.Key words: cross-border
      healthcare, patient mobility, international reimbursements EU health policy,
      Directive 2011/24/EU.

PMID- 27696890
TI  - [Hospital-based Health Technology Assessment].
AB  - Hospital-based HTA (HB-HTA) consists in implementation of assessment activities
      "in" or "for" hospitals; hence, it covers processes and methods supporting
      organization and execution of health technology assessment (HTA) at the level of
      individual hospitals. This process is multidisciplinary, systematic and evidence
      based.HB-HTA objectives and methods differ from the classic utilization of HTA at
      the national regulator level. Most experience and information concerning HB-HTA
      has originated in two large recent projects: activities of the HB-HTA Interest
      Group of the HTAi international association established in 2006, and the AdHopHTA
      European research project (20122015).This paper describes four basic
      organizational models of HB-HTA, their characteristics and utilization in various
      countries and hospital types. Results of the AdHopHTA project are analyzed, and
      recommendations for HB-HTA implementation in Czech hospitals are formulated.Key
      words: hospital-based HTA, medical device, implementation, hospital strategy.

PMID- 27696891
TI  - [Complete and detailed critiques of medical criteria for assessing the degree of
      dependence for the care allowance].
AB  - In 2012 it was applied to medical practice assessor new criteria for assessing
      the degree of dependence for the care allowance. After four years by the Ministry
      of Labour and Social Affairs proposed expansion of the existing activities and at
      the other activities, it is proposed to refine the text. New activities refine or
      complement the existing framework defining the basic needs of life and should
      lead to a more objective and personally assessment of the degree of dependence.
      With the change in legislation expected a growth in the number of applicants for
      assessment General assessment principles and policies remain unchanged.Key words:
      medical assessment service, dependence degree, basic living needs.

PMID- 27696892
TI  - [Hospital chaplain, or "spiritual assistant"? - pitfalls of missing legislative
      framework].
AB  - As military and prison chaplains have been active in the military or prison
      service for many years, nowadays, hospital chaplains have been active in many
      hospitals in the Czech Republic, too. The work of hospital chaplains, however,
      still lacks the necessary legislative framework and being embodied in law, which
      brings some drawbacks. These include primarily non-participation of the ministry
      of health as a contractual partner in the agreement on spiritual care in health
      care, the lack of a framework that would arrange the status of chaplains among
      other health professionals and the related uncertainty regarding career and
      competency profile of a chaplain.Moreover, the ministry has not set clear rules
      for the work of chaplains in hospitals, and due to this fact, it has created the
      space for providing this service also by unqualified persons. This may ultimately
      have a negative impact on patients. It is therefore the responsibility of the
      hospital management to arrange that only professional hospital chaplains sent to
      hospitals on the basis of an agreement between the hospital and the relevant
      church work there.Key words: hospital chaplain, spiritual assistant, health care
      system, legislation.

PMID- 27696893
TI  - New lasiodiplodins from mangrove endophytic fungus Lasiodiplodia sp. 318.
AB  - Two new lasiodiplodins (1-2) together with three known analogues, were isolated
      from a mangrove endophytic fungus, Lasiodiplodia sp. 318#. Their structures were
      established by spectroscopic techniques (1D- and 2D-NMR, HR-ESI-MS, etc.), and
      electronic circular dichroism. Cytotoxic activities of compounds 1-5 were
      evaluated in vitro. Compound 4 was the most potent, with IC50 values of 5.29 MUM
      against MMQ, 13.05 MUM against GH3. Preliminary structural-activity analysis
      indicated that the functional group (resorcinol-3-OH) contributed greatly to the
      binding of Lasiodiplodins to the cytotoxic activities.

PMID- 27696894
TI  - Soil microbial communities of three major Chinese truffles in southwest China.
AB  - Tuber pseudoexcavatum, Tuber sinoaestivum, and Tuber indicum are the 3 most
      important truffles growing in southeast China; however, their cultivation is
      still inefficient owing to the lack of understanding regarding the composition
      and function of the bacterial and fungal communities from the soils around the
      fruit bodies and the ectomycorrhiza of these truffles. The aim of this study was
      to disclose the microbial communities in truffle-producing soils in Huidong
      County, Sichuan, China, by using barcoded pyrosequencing. Approximately 350 000
      quality-controlled sequences were obtained and grouped into 14 025 bacterial
      operational taxonomic units (OTUs) and 4385 fungal OTUs, which included 29
      bacterial and 7 fungal phyla, respectively. The bacterial genus Acidobacterium
      and fungal genera Modicella, Pseudogymnoascus, and Mortierella were significantly
      more abundant in the control soils than in the truffle-producing soils (P <
      0.05), while the bacterial genus Sphingomonas (Alphaproteobacteria) and
      arbuscular mycorrhizal fungal genus Glomus were significantly enriched in truffle
      producing soil than in the control (P < 0.05), indicating their different roles
      within truffle grounds. Notably, some nonfungal organisms detected by 18S rDNA
      pyrosequencing were of high abundance, among which Cercozoa and Ochrophyta were
      significantly (P < 0.05) more abundant in truffle soils than in control soils,
      indicating their interactions with truffles.

PMID- 27696895
TI  - Dereplication of cytotoxic compounds from different parts of Sophora pachycarpa
      using an integrated method of HPLC, LC-MS and 1H-NMR techniques.
AB  - Sophora pachycarpa Schrenk ex C.A.Mey. is an annual plant belonging to the family
      Fabaceae. The cytotoxic activities of methanol-dichloromethane extracts (1:1) of
      different parts of S. pachycarpa were investigated on DU145 (prostate cancer cell
      line) and MCF-7 (breast cancer cell line) cell lines. The root extract of S.
      pachycarpa was the only extract that showed significant cytotoxic activity with
      IC50 values of 39.88 and 16.49 MUg/mL on DU145 and MCF-7 cell lines,
      respectively. The root extract was then subjected to RP-HPLC for further
      fractionations. Among the isolated fractions from root extract, only one of them
      had remarkable cytotoxic effects with IC50 value of 26.43 on MCF-7 and 7.54
      MUg/mL on DU145 cell lines. Further purification led to isolation of a compound
      with IC50 values of 5.44 and 2.44 MUg/mL on MCF-7 and DU145 cell lines,
      respectively. Based on 1H NMR and 13C NMR spectra, together with LC-MS, the
      structure of the purified compound was assigned as the flavonostilbene
      alopecurone A.

PMID- 27696896
TI  - Long-term therapeutic effects of vertebroplasty for painful vertebral compression
      fracture: a retrospective comparative study.
AB  - As a treatment for painful vertebral compression fractures (VCFs), vertebral
      perforation does not require bone cement infusion. Here, we retrospectively
      assessed the long-term therapeutic effects of vertebroplasty in a comparison with
      those of vertebral perforation. The subjects were 64 patients who underwent
      percutaneous vertebroplasty (PVP group) and 67 patients who underwent vertebral
      perforation (Perforation group) between 2006 and 2011 at Takeda general hospital.
      We compared the analgesic effects of the treatments and the incidences of new
      VCFs between the groups at 15 months postsurgery. The pain scores on a visual
      analog scale 15 months postsurgery were 2.3 +/- 2.0 in the PVP group and 2.1 +/-
      1.4 in the Perforation group, a nonsignificant difference (p = .90). The presence
      of vertebral mobility did not influence the analgesic effect in either group. New
      VCFs developed at a significantly higher rate in the PVP group (n = 27, 52%)
      compared to the Perforation group (n = 11, 24%; p = .0017). This difference was
      even greater within 3 months of the surgery, in 19 PVP patients (38%) and two
      Perforation patients (3.0%; p < .0001). However, the incidence after 3 months was
      eight PVP patients and nine Perforation patients, a nonsignificant difference (p
      = .50). The Kaplan-Meier analysis suggested that the new fractures after surgery
      in both treatment groups may occur at the same frequency at around 31 months
      postoperatively. Vertebroplasty is more effective than vertebral perforation in
      relieving pain early in the course of treatment, but over the long term, no
      significant difference in pain was seen between the two treatments. The
      complication of new fractures seen with cement vertebroplasty is only seen after
      the procedure.

PMID- 27696897
TI  - Sleeping Beauty transposition: from biology to applications.
AB  - Sleeping Beauty (SB) is the first synthetic DNA transposon that was shown to be
      active in a wide variety of species. Here, we review studies from the last two
      decades addressing both basic biology and applications of this transposon. We
      discuss how host-transposon interaction modulates transposition at different
      steps of the transposition reaction. We also discuss how the transposon was
      translated for gene delivery and gene discovery purposes. We critically review
      the system in clinical, pre-clinical and non-clinical settings as a non-viral
      gene delivery tool in comparison with viral technologies. We also discuss
      emerging SB-based hybrid vectors aimed at combining the attractive safety
      features of the transposon with effective viral delivery. The success of the SB
      based technology can be fundamentally attributed to being able to insert fairly
      randomly into genomic regions that allow stable long-term expression of the
      delivered transgene cassette. SB has emerged as an efficient and economical
      toolkit for safe and efficient gene delivery for medical applications.

PMID- 27696898
TI  - Estimating genetic structure and diversity of cyanobacterial communities in
      Atlantic forest phyllosphere.
AB  - Cyanobacterial communities on the phyllosphere of 4 plant species inhabiting the
      endangered Brazilian Atlantic Forest biome were evaluated using cultivation
      independent molecular approaches. Total genomic DNA was extracted from cells
      detached from the surface of leaves of Euterpe edulis, Guapira opposita, Garcinia
      gardneriana, and Merostachys neesii sampled in 2 Brazilian Atlantic Forest
      locations along an elevational gradient, i.e., lowland and montane forest. The
      DNA fingerprinting method PCR-DGGE revealed that the cyanobacterial phyllosphere
      community structures were mainly influenced by the plant species; geographical
      location of the plant had little effect. The 16S rRNA gene sequences obtained by
      clone libraries showed a predominance of nitrogen-fixing cyanobacteria of the
      order Nostocales, even though the majority of retrieved operational taxonomic
      units (~60% of the sequences) showed similarity only to uncultured cyanobacteria
      phylotypes. The leaf surface of Guapira opposita had the highest richness and
      diversity of cyanobacteria, whereas the M. neesii (bamboo) had the largest number
      of copies of cyanobacterial 16S rRNA gene per cm2 of leaf. This study
      investigated cyanobacteria diversity and its distribution pattern in Atlantic
      forest phyllosphere. The results indicated that plant species is the main driver
      of cyanobacteria community assemblage in the phyllosphere and that these
      communities are made up of a high diversity of cyanobacterial taxa that need to
      be discovered.

PMID- 27696899
TI  - Active Videogaming in Youth with Physical Disability: Gameplay and Enjoyment.
AB  - OBJECTIVE: For active videogaming (AVG) to be a meaningful, health-enhancing
      physical activity option for youth with physical disability, factors related to
      game performance and enjoyment must be understood. The objective was to explore
      associations between quality of gameplay, controller usage, heart rate (HR),
      physical function, and enjoyment during AVG play in youth with physical
      disability. METHODS: Participants (5 girls, 11 boys, mean age 13.8 +/- 2.7 years)
      played four AVGs on three platforms (Nintendo(r) WiiTM, Sony PlayStation3 Move,
      and Microsoft Xbox(r) Kinect), across three sessions. Participants' primary means
      of mobility were manual (n = 13) and power (n = 3) wheelchairs; majority were
      diagnosed with cerebral palsy or spina bifida. Functional level was assessed
      using 17 International Classification of Functioning, Disability and Health
      mobility items. Participants played each AVG for 8 minutes with a 5-minute rest.
      Quality of gameplay and ability to use controller were recorded on a five-point
      Likert scale. HR was recorded immediately following each game and participants
      completed the Physical Activity Enjoyment Scale (PACES). PACES scores were
      compared across games and correlations were examined among the variables.
      RESULTS: PACES scores were significantly greater for Wii Punch-Out compared to
      Xbox Fitness, Sports Rivals, and Zumba, and for PS3 Sports Champions compared to
      Xbox Zumba. Higher HR was associated with higher quality of gameplay and a higher
      PACES score. As quality of gameplay increased, the PACES score increased.
      CONCLUSION: Game performance and exercise intensity were positively correlated
      with AVG enjoyment in youth with physical disability, specifically mobility
      impairments. Further research is warranted to examine the capacity of AVG play to
      be an enjoyable health-enhancing activity for individuals with physical
      disability.

PMID- 27696900
TI  - Gene flow, recombination, and positive selection in Stenotrophomonas maltophilia:
      mechanisms underlying the diversity of the widespread opportunistic pathogen.
AB  - Stenotrophomonas maltophilia is a global multidrug-resistant human opportunistic
      pathogen in clinical environments. Stenotrophomonas maltophilia is also
      ubiquitous in aqueous environments, soil, and plants. Various molecular typing
      methods have revealed that S. maltophilia exhibits high levels of phenotypic and
      genotypic diversity. However, information regarding the genomic diversity within
      S. maltophilia and the corresponding genetic mechanisms resulting in said
      diversity remain scarce. The genome sequences of 17 S. maltophilia strains were
      selected to investigate the mechanisms contributing to genetic diversity at the
      genome level. The core and large pan-genomes of the species were first estimated,
      resulting in a large, open pan-genome. A species phylogeny was also reconstructed
      based on 344 orthologous genes with one copy per genome, and the contribution of
      four evolutionary mechanisms to the species genome diversity was quantified: 15%
      35% of the genes showed evidence for recombination, 0%-25% of the genes in one
      genome were likely gained, 0%-44% of the genes in some genomes were likely lost,
      and less than 0.3% of the genes in a genome were under positive selection
      pressures. We observed that, among the four main mechanisms, homologous
      recombination plays a key role in maintaining diversity in S. maltophilia. In
      this study, we provide an overview of evolution in S. maltophilia to provide a
      better understanding of its evolutionary dynamics and its relationship with
      genome diversity.

PMID- 27696901
TI  - Collaboration, trouble and repair in multiparty interactions involving couples
      with dementia or aphasia.
AB  - PURPOSE: The aim of the present study was to identify problems with communication
      with persons with aphasia and persons with dementia in a collaborative interview
      setting with their significant others. In particular, to compare interactional
      practices used in order to resolve problems caused by specific symptoms. METHOD:
      Five persons with aphasia and five persons with dementia and their spouses
      participated in the study. Interviews were carried out couple by couple, and the
      interviews had a task-oriented character. The interviews were video and audio
      recorded. All interviews were transcribed. From the transcriptions
      categorisations according to previous literature were made. RESULT: The results
      demonstrated that repair sequences were frequent in interaction involving people
      with aphasia (PWA), and even more so in interaction involving persons with
      dementia (PWD). In general, it was the PWA/PWD that initiated the repair sequence
      more often than the spouse, thus keeping the general rule of a preference for
      self-initiated repair compared to other-initiated repair. CONCLUSION: The active
      involvement of the conversational partners in trouble solving sequences in
      interaction with PWA/PWD demonstrated in the present study indicates that the
      interactional style of the conversational partner to PWA/PWD important. This
      implies that conversation partner training programmes would be useful both for
      PWA and for PWD.

PMID- 27696903
TI  - Early pubertal timing is common among adolescent girl-to-boy sex reassignment
      applicants.
AB  - OBJECTIVES: The aim of our study was to explore whether gender dysphoria in
      adolescent girls is associated with early pubertal timing. METHODS: We compared
      menarcheal timing among 52 adolescent girl-to-boy sex reassignment (SR)
      applicants with that of 644 adolescent girls who participated in an adolescent
      population mental health survey. RESULTS: Of the population girls, 21% presented
      with early (<=11 years), 61% with normative (12-13 years) and 19% with late (>=14
      years) menarcheal timing; among the SR applicants, 42% presented with early, 46%
      with normative and 12% with late menarcheal timing (p = 0.003). The odds ratio
      for SR applicant girls to have early menarcheal timing was 2.7 (95% confidence
      interval (CI) 1.3, 5.7), controlling for age and family structure. CONCLUSION:
      Like emotional and behavioural disorders, gender dysphoria in adolescence is
      associated in girls with early pubertal timing. The finding is discussed in the
      light of literature related to pubertal maturation and mental health.

PMID- 27696902
TI  - Age-dependent acute interference with stem and progenitor cell proliferation in
      the hippocampus after exposure to 1800 MHz electromagnetic radiation.
AB  - To investigate the effects of exposure to an 1800 MHz electromagnetic field on
      cell death and cell proliferation in the developing brain, postnatal day 7 (P7)
      and P21 healthy Kunming mice were randomly assigned into the experimental and
      control groups. The experimental groups were exposed to an 1800 MHz
      electromagnetic field for 8 h daily for three consecutive days. The thymidine
      analog 5-bromo-2-deoxyuridine (BrdU) was injected intraperitoneally 1 h before
      each exposure session, and all animals were sacrificed 24 h after the last
      exposure. Cell death and proliferation markers were detected by
      immunohistochemistry in the dentate gyrus of the hippocampus. Electromagnetic
      exposure has no influence on cell death in the dentate gyrus of the hippocampus
      in P7 and P21 mice as indicated by active caspase-3 immunostaining and Fluoro
      Jade labeling. The basal cell proliferation in the hippocampus was higher in P7
      than in P21 mice as indicated by the number of cells labeled with BrdU and by
      immunohistochemical staining for phosphor-histone H3 (PHH3) and brain lipid
      binding protein (BLBP). Electromagnetic exposure stimulated DNA synthesis in P7
      neural stem and progenitor cells, but reduced cell division and the total number
      of stem cells in the hippocampus as indicated by increased BrdU labeling and
      reduced PHH3 and BLBP labeling compared to P7 control mice. There were no
      significant changes in cell proliferation in P21 mice after exposure to the
      electromagnetic field. These results indicate that interference with stem cell
      proliferation upon short-term exposure to an 1800 MHz electromagnetic field
      depends on the developmental stage of the brain.

PMID- 27696904
TI  - Investigational calcium channel blockers for the treatment of hypertension.
AB  - INTRODUCTION: Voltage-gated Ca2+ channels are the primary route of Ca2+ entry in
      vascular smooth muscle cells, playing a key role in the regulation of arterial
      tone and blood pressure. Since the 60's, L-type Ca2+ channel blockers (CCBs) have
      been widely used for the treatment of hypertension. Areas covered: T-type Ca2+
      channels regulate vascular tone in small-resistance vessels and aldosterone
      secretion, and N-type channels expressed in sympathetic nerve terminals regulate
      the release of neurotransmitters. We performed a literature search in MEDLINE,
      PubMed and ClinicalTrials.gov to identify eligible studies published between
      January 2001 and March 2016 and reviewed the antihypertensive and renoprotective
      effects of four CCBs with different pharmacological profiles: azelnidipine (L
      type), cilnidipine (L-/N-type) and benidipine and efonidipine (L-/T-type CCBs).
      Despite similar blood pressure lowering effects, L/N- and L/T-type CCBs, compared
      with L-type CCBs, decreased intraglomerular pressure, improved renal hemodynamics
      and provided a greater decrease in proteinuria even in patients already treated
      with renin-angiotensin-aldosterone inhibitors. Expert opinion: Dual L/N- and L/T
      type CCBs may exhibit therapeutic advantages over L-type blockers in hypertensive
      patients with chronic kidney disease. Because clinical trials supporting these
      advantages present important biases, further large-scale, long-term comparative
      trials are needed to confirm that these differences translate into improved
      clinical outcomes.

PMID- 27696905
TI  - Association between parent-adolescent communication about sex-related topics and
      HIV testing, United States. 2006-2013.
AB  - Adolescents need information about sex-related topics in order to reduce risk
      behavior and engage in healthy sexual decision-making. Parents have the potential
      to be an important source of this information. Using the 2006-2010 and 2011-2013
      National Survey of Family Growth, we examined associations between parent
      adolescent communication before age 18 about sex-related topics and HIV testing
      among respondents aged 18-24 that ever had sexual intercourse (women = 3893; men
      = 3359). Analyses showed that for both men and women, discussing how to prevent
      HIV/AIDS and how to use a condom with a parent before age 18 were positively
      associated with HIV testing. Among women only, discussions about methods of birth
      control, where to get birth control, and STDs were positively associated with HIV
      testing. Developing strategies and interventions to facilitate parent-adolescent
      communication about sex-related topics, particularly HIV prevention and condom
      use, may be important to increase HIV testing among young women and men.

PMID- 27696906
TI  - The role of fulvestrant in endometrial cancer.
AB  - INTRODUCTION: Endometrial cancer is the most common malignancy of the female
      genital tract in industrialized countries. The traditional treatment of
      endometrial cancer is based on a surgical approach. In recent years, systemic
      endocrine therapy has demonstrated good efficacy in recurrent or metastatic
      setting, delaying progression, ameliorating quality of life and palliating
      symptoms. Areas covered: Phase I and II studies on selective estrogen receptor
      down-regulators used for the treatment of endometrial cancer treatment have been
      reviewed. The pharmacokinetic and pharmacodynamic features of selective receptor
      down-regulators have been also investigated. Expert opinion: Selective estrogen
      receptor down-regulators may exhibit clinical efficacy in the treatment of
      gynecological malignancies due to their pure estrogen receptor antagonist
      properties. However, up to now data are still limited and some unsolved questions
      remain. Fulvestrant has poor oral bioavailability and low pharmacodynamic
      characteristics. Further trials are required to examine new selective estrogen
      receptor down-regulator agents with better pharmacodynamic and pharmacokinetic
      profiles.

PMID- 27696907
TI  - Field calibration of blowfly-derived DNA against traditional methods for
      assessing mammal diversity in tropical forests.
AB  - Mammal diversity assessments based on DNA derived from invertebrates have been
      suggested as alternatives to assessments based on traditional methods; however,
      no study has field-tested both approaches simultaneously. In Peninsular Malaysia,
      we calibrated the performance of mammal DNA derived from blowflies (Diptera:
      Calliphoridae) against traditional methods used to detect species. We first
      compared five methods (cage trapping, mist netting, hair trapping, scat
      collection, and blowfly-derived DNA) in a forest reserve with no recent reports
      of megafauna. Blowfly-derived DNA and mist netting detected the joint highest
      number of species (n = 6). Only one species was detected by multiple methods.
      Compared to the other methods, blowfly-derived DNA detected both volant and non
      volant species. In another forest reserve, rich in megafauna, we calibrated
      blowfly-derived DNA against camera traps. Blowfly-derived DNA detected more
      species (n = 11) than camera traps (n = 9), with only one species detected by
      both methods. The rarefaction curve indicated that blowfly-derived DNA would
      continue to detect more species with greater sampling effort. With further
      calibration, blowfly-derived DNA may join the list of traditional field methods.
      Areas for further investigation include blowfly feeding and dispersal biology,
      primer biases, and the assembly of a comprehensive and taxonomically-consistent
      DNA barcode reference library.

PMID- 27696909
TI  - Generation of Induced Pluripotent Stem Cells with Substitutes for Yamanaka's Four
      Transcription Factors.
AB  - Induced pluripotent stem cells (iPSCs) share many characteristics with embryonic
      stem cells, but lack ethical controversy. They provide vast opportunities for
      disease modeling, pathogenesis understanding, therapeutic drug development,
      toxicology, organ synthesis, and treatment of degenerative disease. However, this
      procedure also has many potential challenges, including a slow generation time,
      low efficiency, partially reprogrammed colonies, as well as somatic coding
      mutations in the genome. Pioneered by Shinya Yamanaka's team in 2006, iPSCs were
      first generated by introducing four transcription factors: Oct 4, Sox 2, Klf 4,
      and c-Myc (OSKM). Of those factors, Klf 4 and c-Myc are oncogenes, which are
      potentially a tumor risk. Therefore, to avoid problems such as tumorigenesis and
      low throughput, one of the key strategies has been to use other methods,
      including members of the same subgroup of transcription factors, activators or
      inhibitors of signaling pathways, microRNAs, epigenetic modifiers, or even
      differentiation-associated factors, to functionally replace the reprogramming
      transcription factors. In this study, we will mainly focus on the advances in the
      generation of iPSCs with substitutes for OSKM. The identification and combination
      of novel proteins or chemicals, particularly small molecules, to induce
      pluripotency will provide useful tools to discover the molecular mechanisms
      governing reprogramming and ultimately lead to the development of new iPSC-based
      therapeutics for future clinical applications.

PMID- 27696910
TI  - Effect of Sex of Embryo on Developmental Competence, Epigenetic Status, and Gene
      Expression in Buffalo (Bubalus bubalis) Embryos Produced by Hand-Made Cloning.
AB  - Buffalo embryos were produced by hand-made cloning using skin fibroblasts from
      male and female buffaloes (n = 4 each) as donor cells for examining the effect of
      sex. Although the rate of blastocyst formation (43.8% +/- 1.31% vs. 42.2% +/-
      1.22%) was similar, the total cell number (333 +/- 10.4 vs. 270 +/- 10.9) was
      higher (p < 0.05) whereas the apoptotic index (6.39 +/- 0.25 vs. 8.52 +/- 0.38)
      was lower (p < 0.05) for male than for female blastocysts. In the blastocysts,
      the global level of H3K18ac was found to be in the following order:
      male>female>IVF (in vitro fertilization) blastocysts (p < 0.05). The global level
      of H3K9me2 was not significantly different between male and female blastocysts
      and was higher (p < 0.05) compared with that in their IVF counterparts. The
      relative mRNA abundance of X-chromosome-linked (XIST, HPRT, PGK, and G6PD),
      apoptosis- (CASPASE3) and pregnancy-related genes (IFN-tau) was significantly
      higher (p < 0.05) whereas that of DNMT1 was significantly lower (p < 0.05) in
      female than in male blastocysts; however, in the case of apoptosis- (BCL-XL) and
      developmental competence-related genes (IGF1R and OCT4), the expression level was
      similar between the two groups. The gene expression level of OCT4 and IFN-tau but
      not of IGF1R was significantly lower (p < 0.05) in cloned than in IVF
      blastocysts. This study demonstrates that the epigenetic status, quality, and
      expression level of several genes but not the developmental competence are
      affected by the sex of cloned embryos.

PMID- 27696908
TI  - Decoding P4-ATPase substrate interactions.
AB  - Cellular membranes display a diversity of functions that are conferred by the
      unique composition and organization of their proteins and lipids. One important
      aspect of lipid organization is the asymmetric distribution of phospholipids
      (PLs) across the plasma membrane. The unequal distribution of key PLs between the
      cytofacial and exofacial leaflets of the bilayer creates physical surface tension
      that can be used to bend the membrane; and like Ca2+, a chemical gradient that
      can be used to transduce biochemical signals. PL flippases in the type IV P-type
      ATPase (P4-ATPase) family are the principle transporters used to set and repair
      this PL gradient and the asymmetric organization of these membranes are encoded
      by the substrate specificity of these enzymes. Thus, understanding the mechanisms
      of P4-ATPase substrate specificity will help reveal their role in membrane
      organization and cell biology. Further, decoding the structural determinants of
      substrate specificity provides investigators the opportunity to mutationally tune
      this specificity to explore the role of particular PL substrates in P4-ATPase
      cellular functions. This work reviews the role of P4-ATPases in membrane biology,
      presents our current understanding of P4-ATPase substrate specificity, and
      discusses how these fundamental aspects of P4-ATPase enzymology may be used to
      enhance our knowledge of cellular membrane biology.

PMID- 27696911
TI  - Alpha-A-Crystallin Protects Lens Epithelial Cell-Derived iPSC-Like Cells Against
      Apoptosis Induced by Oxidative Stress.
AB  - Cataract, the leading cause of blindness worldwide, is caused by the apoptosis of
      lens epithelial cells (LECs). alphaA-crystallin is a major structural protein of
      the lens. However, the antiapoptotic function of alphaA-crystallin in lens stem
      cells remains unclear. In this study, primary LECs were isolated from postnatal 3
      5 days of SD rats and transfected by Sendai virus loaded with four factors,
      OCT3/4, Sox2, c-Myc, and Klf4, to induced pluripotent stem cells (iPSCs). LEC
      iPSC-like cells were identified by immunofluorescent staining. CryalphaA-specific
      shRNA lentivirus was used to knockdown alphaA-crystallin in LEC-derived iPSC-like
      cells, which were treated with tert-Butyl hydroperoxide. The apoptosis of LEC
      iPSC-like cells was examined by flow cytometry. We reprogrammed LECs and obtained
      embryonic stem cell-like colonies. LEC-iPSC-like cells with normal karyotype
      expressed pluripotent markers such as SSEA-4, TRA-1-60, and TRA-1-81. Knockdown
      of alphaA-crystallin increased the apoptosis of LEC-iPSC-like cells and rendered
      them less resistant to oxidation stress induced by tert-Butyl hydroperoxide. In
      conclusion, LECs could be reprogrammed into iPSC-like cells and alphaA
      crystallins could protect LEC-iPSC-like cells from oxidation stress-induced
      apoptosis.

PMID- 27696913
TI  - Design, synthesis, cytotoxicities and DNA cleavage activities of dibenzoxepine
      and isoquinoline derivatives starting from dehydroabietylamine.
AB  - A series of novel hexahydrodibenzoxepine and quinazoline derivatives were
      designed and synthesized starting from dehydroabietylamine. The cytotoxicities of
      the compounds against L02 and HepG2 cell lines were investigated. Meanwhile, the
      plasmid DNA (Escherichia coli) cleavage of several heterocyclic derivatives was
      studied. These compounds exhibit remarkable activities on plasmid DNA pBR322. Our
      study provides useful information for developing new and more potent antitumor
      agents.

PMID- 27696914
TI  - Maternal hepatitis B surface antigen carrier status and its impact on neonatal
      outcomes: a cohort study of 21 947 singleton newborns in China.
AB  - OBJECTIVE: To explore the impact of maternal hepatitis B surface antigen (HBsAg)
      carrier status on neonatal outcomes. METHODS: A retrospective cohort study was
      conducted using data from medical records database of six hospitals in China.
      Information on maternal characteristics and selected neonatal outcomes was
      retrieved for all women who delivered singleton infants between 1 January 2009
      and 31 December 2010. RESULTS: A total of 21 947 singleton newborns and their
      mothers were included. The prevalence of maternal HBsAg positivity was 4.2% (95%
      confidence interval (CI) 3.9-4.5%). Compared with infants born to HBsAg-negative
      women, infants born to HBsAg-positive mothers were more than twice more likely to
      have a malformation before (adjusted odds ratio (aOR) 2.23, 95% CI 1.15-4.30) and
      at birth (aOR 2.66, 95% CI 1.38-5.14), but were less likely to be macrosomia (aOR
      0.67, 95% CI 0.47-0.96). No statistically significant association was found
      between maternal HBsAg positivity and preterm birth (aOR 1.20, 95% CI 0.95-1.51),
      low birth weight (aOR 1.24, 95% CI 0.91-1.69), and Apgar scores at 1 min (aOR
      0.88, 95% CI 0.49-1.57) and 5 min (aOR 1.84, 95% CI 0.89-3.81). CONCLUSION:
      Maternal HBsAg positivity may be associated with a higher risk of congenital
      malformation.

PMID- 27696916
TI  - Experience of Psychotropic Medication -An Interview Study of Persons with
      Psychosis.
AB  - Psychotropic drugs, particularly antipsychotic types, are a cornerstone of the
      treatment of people with psychosis. Despite numerous studies showing that drug
      treatment with psychotropic drugs initially alleviates psychiatric symptoms, the
      proportion of people with mental health problems and symptoms that do not follow
      doctors' prescriptions, thus exhibiting so-called non-adherence, is considerable.
      Non-adherence is predominantly seen as a clinical feature and as a patient
      characteristic that is especially due to patients' poor understanding that they
      are ill. There is also a widespread notion that non-adherence is of great
      disadvantage to the patient. This article is based on interviews with 19 persons
      diagnosed with psychosis. It challenges the notion of patients being either
      adherent or non-adherent to the doctor's orders. The findings show that persons
      with psychosis are active agents when it comes to adjusting medication. The
      interviewees created their own strategies to gain power over treatment with
      psychotropic drugs. The most common strategies were to adjust the doses or take
      breaks of varying lengths from the medication. These deviations from
      prescriptions were important to conceal, not only from their own psychiatrists,
      but from all psychiatric staff.

PMID- 27696915
TI  - An mHealth monitoring system for traditional birth attendant-led antenatal risk
      assessment in rural Guatemala.
AB  - Limited funding for medical technology, low levels of education and poor
      infrastructure for delivering and maintaining technology severely limit medical
      decision support in low- and middle-income countries. Perinatal and maternal
      mortality is of particular concern with millions dying every year from
      potentially treatable conditions. Guatemala has one of the worst maternal
      mortality ratios, the highest incidence of intra-uterine growth restriction
      (IUGR), and one of the lowest gross national incomes per capita within Latin
      America. To address the lack of decision support in rural Guatemala, a smartphone
      based system is proposed including peripheral sensors, such as a handheld Doppler
      for the identification of foetal compromise. Designed for use by illiterate birth
      attendants, the system uses pictograms, audio guidance, local and cloud
      processing, SMS alerts and voice calling. The initial prototype was evaluated on
      22 women in highland Guatemala. Results were fed back into the refinement of the
      system, currently undergoing RCT evaluation.

PMID- 27696918
TI  - Early Psychological Preventive Intervention For Workplace Violence: A Randomized
      Controlled Explorative and Comparative Study Between EMDR-Recent Event and
      Critical Incident Stress Debriefing.
AB  - This randomized controlled trial study aims to investigate the efficacy of an
      early psychological intervention called EMDR-RE compared to Critical Incident
      Stress Debriefing on 60 victims of workplace violence, which were divided into
      three groups: 'EMDR-RE' (n = 19), 'CISD' (n = 23), and 'delayed EMDR-RE' (n =
      18). EMDR-RE and CISD took place 48 hours after the event, whilst third
      intervention was delayed by an additional 48 hours. Results showed that after 3
      months PCLS and SUDS scores were significantly lower with EMDR-RE and delayed
      EMDR-RE compared to CISD. After 48 hours and 3 months, none of the EMDR-RE
      treated victims showed PTSD symptoms.

PMID- 27696919
TI  - Corrigendum.

PMID- 27696917
TI  - Lower serotonin level and higher rate of fibromyalgia syndrome with advancing
      pregnancy.
AB  - OBJECTIVE: The aim of the study is to investigate the relationship between
      changes in serotonin levels during pregnancy and fibromyalgia syndrome (FS) and
      the relationships between FS and the physical/psychological state, biochemical
      and hormonal parameters, which may be related to the musculoskeletal system.
      STUDY DESIGN: This study is a prospective case-control study conducted with 277
      pregnant women at the obstetric unit of Ankara University Faculty of Medicine, in
      the period between January and June 2015. FS was determined based on the presence
      or absence of the 2010 ACR diagnostic criteria and all the volunteers were asked
      to answer the questionnaires as Fibromyalgia Impact Criteria (FIQ), Widespread
      Pain Index (WPI), Symptom Severity Scale (SS), Beck Depression Inventory and
      Visual Analog Scale (VAS). Biochemical and hormonal markers (glucose, TSH, T4, Ca
      (calcium), P (phosphate), PTH (parathyroid hormone) and serotonin levels)
      relating to muscle and bone metabolism were measured. RESULTS: In the presence of
      fibromyalgia, the physical and psychological parameters are negatively affected
      (p < 0.001). There was no significant difference between the fibromyalgia and
      control groups in terms of glucose, Ca (calcium), P (phosphorus), PTH
      (parathyroid hormone), TSH (thyroid stimulant hormone), fT4 (free T4) levels (p =
      0.060, 0.799, 0.074, 0.104, 0.797, 0.929, respectively). A reduction in serotonin
      levels may contribute to the development of fibromyalgia but this was not
      statistically significant. The Beck Depression Inventory scale statistically
      showed that increasing scores also increase the risk of fibromyalgia (p <0.001).
      CONCLUSION: Our study has shown that serotonin levels in women with FS are lower
      than the control group and that serotonin levels reduce as pregnancy progresses.
      Anxiety and depression in pregnant women with FS are higher than the control
      group. The presence of depression increases the likelihood of developing FS at a
      statistically significant level. Serotonin impairment also increases the chance
      of developing FS, but this correlation has not been shown to be statistically
      significant.

PMID- 27696920
TI  - Stress distribution on short implants with different designs: a photoelastic
      analysis.
AB  - Short dental implants have been used as an attempt to avoid bone grafts surgery,
      however there are few literature reports that evaluate changes to their design.
      Therefore, the aim of this study was to assess the effect of different short
      implant design on stress distribution through photoelastic analysis. Six external
      hexagon (5 * 5 mm) short dental implants with different design were used. Each
      group was treated with a single crown and a three element fixed partial dental
      prosthesis, resulting in a total of 12 photoelastic models. The assembling
      photoelastic model-implant-prosthesis was set in a circular polariscope where
      loads of 100N were applied on the occlusal surface with a Universal Test Machine
      (UTM). The tension fringes were photographed and later assessed qualitatively by
      a graphic software (Adobe Photoshop). Less high-intensity fringes were observed
      on the short implants with triangular threads, short external hexagon and flat
      apical profile. In conclusion, the macrodesign influenced the amount of stress
      distributed to the bone when short dental implants are placed.

PMID- 27696921
TI  - Prenatal identification of CHD murmur using four segment phonocardiographic
      signal analysis.
AB  - Congenital heart defects (CHD) are one of the utmost birth defects present in the
      neonatal after birth and a big challenge for the researchers to identify the
      structural abnormality during the antepartum period. An algorithm is presented
      here to identify the presence of CHD through foetal phonocardiographic (fPCG)
      signals. The recorded fPCG is decomposed using Daubechies4 wavelet with sub-level
      threshold to remove the noise in the signal. The Shannon energy is used to
      identify the different peaks of signals and then S1 and S2 according to the
      intervals between adjacent peaks. The signal is segmented into four important
      parts: S1, S1S2, S2 and S2S1. The FFT is used to identify the frequency component
      present in four segments which in turn indicates the presence of pathological
      murmur that may turn into CHD. The algorithm is tested on 25 samples with
      accuracy rate 88% in identifying the presence of a murmur.

PMID- 27696922
TI  - Evaluation of an in vitro screening model to assess phosgene inhalation injury.
AB  - Therapeutic development against exposure to toxic gases is hindered by the lack
      of appropriate models to evaluate candidate compounds prior to animal efficacy
      studies. In this study, an in vitro, air-liquid interface exposure model has been
      tested to examine its potential application for screening treatments for phosgene
      (carbonyl chloride)-induced pulmonary injury. Epithelial cultures on Transwell(r)
      inserts, combined with a Vitrocell(r) exposure apparatus, provided a
      physiologically relevant exposure environment. Differentiated human bronchial
      epithelial (16HBE) cultures were exposed for 8 min to phosgene ranging from 0 to
      64 ppm and assessed for changes in transepithelial electrical resistance (TEER,
      epithelial barrier integrity), cellular viability (XTT) and post-exposure (PE)
      cellular metabolic energy status. Exposure to phosgene concentrations >=8 ppm
      caused dose-dependent and significant decreases in TEER and XTT which did not
      recover within 24-h PE. In addition, at 64 ppm the rate of oxidative glutamine
      metabolism was significantly inhibited at 6 and 24 h after exposure. Glycolytic
      activities (glucose utilization and lactate production) were also inhibited, but
      to a lesser extent. Decreased glycolytic function can translate to insufficient
      energy sources to counteract barrier function failure. Consistent and sensitive
      markers of phosgene exposure were TEER, cell viability and decreased metabolism.
      As such, we have assessed an appropriate in vitro model of phosgene inhalation
      that produced quantifiable alterations in markers of lung cell metabolism and
      injury in human airway epithelial cells. Data indicate the suitability of this
      model for testing classes of anti-edemagenic compounds such as corticosteroids or
      phosphodiesterase inhibitors for evaluating phosgene therapeutics.

PMID- 27696923
TI  - Repeated restraint stress produces acute and chronic changes in hemodynamic
      parameters in rats.
AB  - Noninvasive hemodynamic measurements in rats require placing animals in
      restrainers. To minimize restraint stress-induced artifacts several habituation
      protocols have been proposed, however, the results are inconclusive. Here, we
      evaluated if a four-week habituation is superior to a shorter habituation, or no
      habituation. This is the first study comparing different habituation protocols
      with the use of four-week continuous telemetry measurements. We did the
      experiments on male, 16-week old, Sprague-Dawley rats. Continuous recordings of
      mean arterial blood pressure (MABP) and heart rate (HR) were made before and
      during habituation protocols. Rats were subjected either to control (four weeks
      of restraint-free recordings, n = 5) or two-week (seven restraints, n = 6) or
      four-week (14 restraints, n = 6) restraint sessions. The restraint protocols
      included placement of rats in the middle of the dark phase into plastic
      restrainers as used for tail-cuff measurements. Restraint lasted for 60 min, and
      was repeated every second day. Each restraint significantly increased MABP (by 15
      25 mmHg) and HR (by 40-120 beats/min). Exposure to the restraint protocols
      decreased diurnal variation in MABP. There was no hemodynamic adaptation to
      repeated restraint, and no significant difference in hemodynamic response to
      restraint among controls, the two-week and the four-week groups. In conclusion,
      our study indicates that measurements in restrained rats are not likely being
      made without stress-induced changes in MABP. Moreover, in hemodynamic studies in
      repeatedly restrained rats longer habituation is not superior to shorter
      habituation.

PMID- 27696925
TI  - Corrigendum.

PMID- 27696924
TI  - The RNA-editing deaminase ADAR is involved in stress resistance of Artemia
      diapause embryos.
AB  - The most widespread type of RNA editing, conversion of adenosine to inosine (A
      >I), is catalyzed by two members of the adenosine deaminase acting on RNA (ADAR)
      family, ADAR1 and ADAR2. These enzymes edit transcripts for neurotransmitter
      receptors and ion channels during adaption to changes in the physical
      environment. In the primitive crustacean Artemia, when maternal adults are
      exposed to unfavorable conditions, they release diapause embryos to withstand
      harsh environments. The aim of the current study was therefore to elucidate the
      role of ADAR of Artemia diapause embryos in resistance to stress. Here, we
      identified Artemia ADAR (Ar-ADAR), which harbors a putative nuclear localization
      sequence (NLS) and two double-stranded RNA-binding motifs (dsRBMs) in the amino
      terminal region and an adenosine deaminase (AD) domain in the carboxyl-terminal
      region. Western blot and immunofluorescence analysis revealed that Ar-ADAR is
      expressed abundantly in post-diapause embryos. Artemia (n = 200, three
      replicates) were tested under basal and stress conditions. We found that Ar-ADAR
      was significantly induced in response to the stresses of salinity and heat-shock.
      Furthermore, in vivo knockdown of Ar-ADAR (n = 100, three replicates) by RNA
      interference induced formation of pseudo-diapause embryos, which lack resistance
      to the stresses and exhibit high levels of apoptosis. These results indicate that
      Ar-ADAR contributes to resistance to stress in Artemia diapause embryos.

PMID- 27696926
TI  - Development of a new miniaturized bioreactor for axon stretch growth.
AB  - Peripheral nerve injury requires a physical bridge across the lesion, which is
      limited by the insufficient supply of donor nerves. Here, we developed a new
      miniaturized bioreactor system for axon stretch growth. Dorsal root ganglia
      explants were first placed on two adjoining substrates and formed new synaptic
      connections. The axon bundles across the border between the top and bottom
      membranes were then stretched in a stepwise fashion by a microstepper motor
      system. After several days of stretch, the axon tracts could reach lengths that
      could develop into living nervous tissue constructs. In order to achieve
      appropriate neuronal culture to stimulate physiological conditions during axon
      stretch, we tested a variety of coating methods. Based on these results, the
      elongator substrates were coated with both poly-D-lysine and rat-tail collagen to
      maximize the number of axon bundles. Additionally, we found that increasing the
      axon stretch by 1[Formula: see text][Formula: see text]m at each step resulted in
      the highest stability. The bridging axons adapted to the stretch by increasing
      their length from 500[Formula: see text][Formula: see text]m to 5.94[Formula: see
      text]mm over 7 days of stretch growth. Immunocytochemical analysis confirmed that
      beta-III-tubulin, a major cytoskeletal constituent and neuronal marker, was
      present along axons. The findings demonstrate that bioreactor has the potential
      to generate transplant materials to address neural repair.

PMID- 27696927
TI  - Classification of the fragrant styles and evaluation of the aromatic quality of
      flue-cured tobacco leaves by machine-learning methods.
AB  - During commercial transactions, the quality of flue-cured tobacco leaves must be
      characterized efficiently, and the evaluation system should be easily
      transferable across different traders. However, there are over 3000 chemical
      compounds in flue-cured tobacco leaves; thus, it is impossible to evaluate the
      quality of flue-cured tobacco leaves using all the chemical compounds. In this
      paper, we used Support Vector Machine (SVM) algorithm together with 22 chemical
      compounds selected by ReliefF-Particle Swarm Optimization (R-PSO) to classify the
      fragrant style of flue-cured tobacco leaves, where the Accuracy (ACC) and
      Matthews Correlation Coefficient (MCC) were 90.95% and 0.80, respectively. SVM
      algorithm combined with 19 chemical compounds selected by R-PSO achieved the best
      assessment performance of the aromatic quality of tobacco leaves, where the PCC
      and MSE were 0.594 and 0.263, respectively. Finally, we constructed two online
      tools to classify the fragrant style and evaluate the aromatic quality of flue
      cured tobacco leaf samples. These tools can be accessed at
      http://bioinformatics.fafu.edu.cn/tobacco .

PMID- 27696928
TI  - Introduction to the special issue on GIW 2016.

PMID- 27696929
TI  - Effects of Psychoeducation Given to Caregivers of People With a Diagnosis of
      Schizophrenia.
AB  - The aim of this study was to evaluate the effectiveness of psychoeducation given
      to caregivers of patients diagnosed with schizophrenia on their perceptions of
      burden and on clinical course of patients. This was a quasi-experimental study
      with pre-post tests and a control group and designed as a nonrandomized
      controlled intervention trial. While the patients in both the intervention and
      the control group received treatment as usual (TAU), only the caregivers in the
      study group were offered two sessions of psychoeducation a week for one month,
      with a total of eight sessions. Effectiveness of the psychoeducation given was
      evaluated by comparing scores of Perceived Family Burden Scale (PFBS) and
      Positive and Negative Syndrome Scale (PANSS) obtained before and three months
      after delivery between the intervention and the control groups. Mean PFBS burden
      scores of the control group at baseline and follow-up were 45.7 and 44.5,
      respectively. Mean PFBS burden scores of the intervention group were 45.2 at
      baseline and 38.6 at follow-up. Analysis of variance revealed significant and
      medium to large size interaction effects of time and group factors on total
      burden scores of family members (F1.58 = 5.59; p < 0.05; etap2 = 0.09) and on
      total PANSS scores of patients (F1.58 = 104.78; p < 0.001; etap2 = 0.64). Our
      findings suggest that psychoeducation offered to the caregivers along with TAU
      offered to patients might result in diminished perceptions of burden among
      caregivers and enhanced improvement in the clinical course of patients as a
      result of psychoeducation offered to caregivers.

PMID- 27696930
TI  - Dopamine DRD2 polymorphism (DRD2/ANNK1-Taq1A) is not a significant risk factor in
      writer's cramp.
AB  - Writers' cramp is a movement disorder with dystonic co-contraction of fingers and
      hand during writing and is part of the clinical spectrum of focal dystonias.
      Previous studies showed reduced striatal dopamine receptor D2 (DRD2) availability
      in dystonia. The expression of D2 receptors is modulated by a DRD2/ANKK1-Taq1A
      polymorphism (rs1800497). This study addresses the question of whether the
      DRD2/ANKK1-Taq1A polymorphism is a risk factor for writer's cramp. We determined
      the DRD2/ANKK1-Taq1A polymorphism 34 patients with writer's cramp compared to 67
      age matched controls. 35.3% of the patients and 31.3% of our controls were
      assigned to the A1 genotype status (p = .7). Therefore DRD2/ANKK1-Taq1A gene is
      not a significant risk factor in the evolution of writer's cramp.

PMID- 27696931
TI  - Targeting the vasculature: anti-angiogenic agents for malignant mesothelioma.
AB  - INTRODUCTION: Malignant mesothelioma (MM) is an aggressive malignancy of the
      pleura and other serosal membranes originating from mesothelial cells that,
      despite decades of research, continues to have limited therapeutic options and is
      associated with a poor prognosis. Areas covered: MMs induce a strong inflammatory
      response that is also associated with neoangiogenesis and activation of
      proangiogenic factors. Given this, several anti-angiogenic agents have been
      trialled in a variety of malignancies including mesothelioma. Herein we summarise
      the role of angiogenesis in MM and the current available data targeting these
      pathways. Expert commentary: The addition of bevacizumab to cisplatin/pemetrexed
      chemotherapy is currently a therapeutic option with a proven 2.7 month overall
      survival benefit in fit patients less than 75. Other antiangiogenics such as
      nintedinib show early promise, although the Phase III trial results are eagerly
      awaited before this therapy enters treatment paradigms. Beyond this, it is likely
      that combinations of antiangiogenics with immunotherapies will be investigated in
      future studies.

PMID- 27696932
TI  - Improving diagnostic molecular tests to monitor urothelial carcinoma recurrence.
AB  - INTRODUCTION: The high recurrence rates associated with non-muscle invasive
      bladder cancer require close surveillance with cystoscopy, an invasive and
      expensive procedure with risk of missing cancer. Finding an accurate urinary
      biomarker that can detect recurrent disease would represent a significant
      advancement in management. Areas covered: This review summarizes the commercially
      available urinary biomarkers including cytology, UroVysion, BTA, NMP22, uCyt+,
      and Cxbladder assays. Additionally, we review recent investigational urinary
      biomarkers that hold promise in bladder cancer surveillance. Expert commentary:
      The quest for a reliable urinary biomarker for bladder cancer is decades-old and
      seems intuitive given the direct contact of urine with malignant urothelium.
      Beyond urine cytology, there are many commercially-available products approved
      for surveillance. However, none of the assays are routinely used due to lack of
      sensitivity and/or specificity. As such, emerging technologies, in particular the
      '-omic' technologies have resulted in a proliferation of promising reports on
      novel biomarkers in recent literature.

PMID- 27696933
TI  - High-flavanol and high-theobromine versus low-flavanol and low-theobromine
      chocolate to improve uterine artery pulsatility index: a double blind randomized
      clinical trial.
AB  - OBJECTIVE: To evaluate the impact of high-flavanol and high-theobromine (HFHT)
      chocolate in women at risk of preeclampsia (PE). STUDY DESIGN: We conducted a
      single-center randomized controlled trial including women with singleton
      pregnancy between 11 and 14 weeks gestation who had bilateral abnormal uterine
      artery (UtA) waveforms (notching) and elevated pulsatility index (PI).
      Participants were randomized to either HFHT or low-flavanol and low-theobromine
      (LFLT) chocolate (30 grams daily for a total of 12 weeks). UtA PI, reported as
      multiple of medians (MoM) adjusted for gestational age, was assessed at baseline
      and 12 weeks after randomization. RESULTS: One hundred thirty-one women were
      randomized with mean gestational age of 12.4 +/- 0.6 weeks and a mean UtA PI of
      1.39 +/- 0.31 MoM. UtA PI adjusted for gestational age significantly decreased
      from baseline to the second visit (12 weeks later) in the two groups (p < 0.0001)
      but no significant difference was observed between the groups (p = 0.16).
      CONCLUSIONS: Compared with LFLT chocolate, daily intake of HFHT chocolate was not
      associated with significant changes of UtA PI. Nevertheless, the improvement
      observed in both groups suggests that chocolate could improve placental function
      independently of flavanol and/or theobromine content.

PMID- 27696934
TI  - Effects of Vegetable Oils with Different Fatty Acid Compositions on Cognition and
      Memory Ability in Abeta25-35-Induced Alzheimer's Disease Mouse Model.
AB  - In this study, we aimed to investigate the protective effect of three kinds of
      vegetable oils with different fatty acid compositions against cognitive
      impairment in an Alzheimer's disease (AD) mouse model. After
      intracerebroventricular injection of amyloid beta25-35 (Abeta25-35) into the
      brain of institute of cancer research mice, olive oil (rich in oleic acid,
      C18:1), corn oil (rich in linoleic acid, C18:2), and perilla oil (rich in alpha
      linolenic acid [ALA], C18:3) were administered at the oral dose of 500 mg/kg/day
      for 14 days. The results revealed that Abeta25-35 induced learning and memory
      dysfunction according to the T-maze, novel object recognition, and Morris water
      maze tests. Among the three vegetable oils, however, the perilla oil group of
      mice showed marked attenuation of cognitive impairment, that is, a greater number
      of explorations on a new route/object than on an old route/object in the T-maze
      and novel object recognition tests. In the Morris water maze test, perilla oil
      decreased the time to reach the platform and increased the number of crossings
      over the target quadrant in which the platform was located previously.
      Furthermore, the beneficial effect of perilla oil supplementation on oxidative
      stress was reflected in the inhibition of malondialdehyde and nitric oxide (NO)
      production in Abeta25-35-injected mice. We also found that perilla oil
      downregulated protein expression levels of inducible NO synthase and
      cyclooxygenase-2 and upregulated brain-derived neurotrophic factor. These
      findings showed that ALA-rich perilla oil has a potential for prevention or
      treatment of neurodegenerative diseases such as AD.

PMID- 27696936
TI  - Context-specific adjustment of cognitive control: Transfer of adaptive control
      sets.
AB  - Cognitive control protects processing of relevant information from interference
      by irrelevant information. The level of this processing selectivity can be
      flexibly adjusted to different control demands (e.g., frequency of conflict)
      associated with a certain context, leading to the formation of specific context
      control associations. In the present study we investigated the robustness and
      transferability of the acquired context-control demands to new situations. In
      three experiments, we used a version of the context-specific proportion
      congruence (CSPC) paradigm, in which each context (e.g., location) is associated
      with a specific conflict frequency, determining high and low control demands. In
      a learning phase, associations between context and control demands were
      established. In a subsequent transfer block, stimulus-response mappings, whole
      task sets, or context-control demands changed. Results showed an impressive
      robustness of context-control associations, as context-specific adjustments of
      control from the learning phase were virtually unaffected by new stimuli and
      tasks in the transfer block. Only a change of the context-control demand
      eliminated the context-specific adjustment of control. These findings suggest
      that context-control associations that have proven to be adaptive in the past are
      continuously applied despite major changes in the task structure as long as the
      context-control associations remain the same.

PMID- 27696938
TI  - A novel modelling and simulation method of hip joint surface contact stress.
AB  - Understanding the hip joint surface contact stress distribution characteristics
      is helpful to determine hip joint biomechanical features and abnormal
      pathological behavior. Firstly, a 3-dimensional static hip joint biomechanical
      model is built using analytical method of model in order to study biomechanical
      properties including bearing area, stress distribution and the peak value of the
      contact stress of the femoral head, which reveals the relationship between the
      biomechanical properties and its geometric parameters. Secondly, based on the
      finite element analysis of the hip joint model, the contact stress distribution
      on the surface of femoral head is acquired under the condition of the different
      joint force and the acetabulum coverage rate. Finally, according to the
      evaluation of the femoral head surface stress and contact stress peak under
      different load distribution, accuracy and universality of the biomechanical model
      is verified.

PMID- 27696937
TI  - Transcriptional control by G-quadruplexes: In vivo roles and perspectives for
      specific intervention.
AB  - G-quadruplexes are non-canonical DNA secondary structures involved in several
      genomic and molecular processes. Here, we summarize the main G-quadruplex
      features and evidences proving the in vivo role on the transcriptional regulation
      of genes required for zebrafish embryonic development. We also discuss
      alternative strategies for specifically interfering G-quadruplex in vivo.

PMID- 27696935
TI  - The evolution of recombinant thrombolytics: Current status and future directions.
AB  - Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity,
      hypertension, raised blood lipids, diabetes and age-related risks. The use of
      classical antiplatelet and anticoagulant therapies combined with surgical
      intervention helped to clear blood clots during the inceptive years. However, the
      discovery of streptokinase and urokinase ushered the way of using these enzymes
      as thrombolytic agents to degrade the fibrin network with an issue of systemic
      hemorrhage. The development of second generation plasminogen activators like
      anistreplase and tissue plasminogen activator partially controlled this problem.
      The third generation molecules, majorly t-PA variants, showed desirable
      properties of improved stability, safety and efficacy with enhanced fibrin
      specificity. Plasmin variants are produced as direct fibrinolytic agents as a
      futuristic approach with targeted delivery of these drugs using liposome
      technlogy. The novel molecules from microbial, plant and animal origin present
      the future of direct thrombolytics due to their safety and ease of
      administration.

PMID- 27696939
TI  - Are Dietary Patterns Associated with Depression in U.S. Adults?
AB  - Nutrition is one of the most important modifiable determinants for and
      consequences of both mental and physical heath. Depression has become an
      increasingly important public health issue. We tested whether dietary patterns
      derived from food group intake are associated with depression in U.S. adults in a
      cross-sectional study with national population. This study included 4180 men and
      4196 women aged 20-79 years in the 2007-2010 National Health and Nutrition
      Examination Surveys (NHANES), with complete data of one 24-h dietary recall,
      sociodemographics, lifestyles, and Patient Health Questionnaires (PHQ-9) for
      screening depression. Two major dietary patterns identified by factor analysis
      were investigated for their associations with presence of depression (PHQ-9 score
      >=10) by using linear and multivariate logistic regressions. One of two major
      patterns, labeled "Western" dietary pattern was characterized by high intakes of
      nonwhole grain, white potatoes, cheese, meat, discretionary oil and fat, and
      added sugar; the second dietary pattern that was labeled "Healthy" dietary
      pattern was characterized by high intakes of whole grains, vegetables, fruits,
      fish, nuts and seeds. The "Western" dietary pattern was not significantly
      associated with depression in both men and women. The "Healthy" dietary pattern
      scores were inversely associated with the PHQ-9 depression scores and odd ratios
      (ORs) of depression after adjustment for covariates in women but not in men. The
      OR of depression in women with the highest quintile of "Healthy" dietary pattern
      scores was 0.60 (95% confidence interval [CI]: 0.42-0.85, P < .001) compared to
      the lowest quintile as a reference. These findings warrant future interventions
      or clinical trials in elucidating causal and effect relations of depression and
      dietary patterns, an important public health concern.

PMID- 27696950
TI  - The beat of social cognition: Exploring the role of heart rate variability as
      marker of mentalizing abilities.
AB  - There is a long-standing debate on the influence of physiological signals on
      social behavior. Recent studies suggested that heart rate variability (HRV) may
      be a marker of social cognitive processes. However, this evidence is preliminary
      and limited to laboratory studies. In this study, 25 participants were assessed
      with a social cognition battery and asked to wear a wearable device measuring HRV
      for 6 consecutive days. The results showed that reduced HRV correlated with
      higher hostility attribution bias. However, no relationship was found between HRV
      and other social cognitive measures including facial emotion recognition, theory
      of mind or emotional intelligence. These results suggest that HRV may be linked
      to specific social cognitive processes requiring online emotional processing, in
      particular those related to social threat. These findings are discussed in the
      context of the neurovisceral integration model.

PMID- 27696955
TI  - Interventions to reduce intimate partner violence perpetration among people with
      substance use disorders.
AB  - The social and economic cost of intimate partner violence (IPV) is exorbitant and
      highlights the need for policy reform as it pertains to IPV interventions at a
      global level. There are multiple variables associated with the aetiology of IPV
      and, hence, multiple treatment needs must be considered. Substance use is one of
      several factors likely to influence the occurrence of IPV, but often goes
      unaddressed in standard treatment approaches. This review will discuss several
      treatment models for substance using offenders of IPV, including Psycho
      educational Models, Cognitive Behavioural Therapy, Couples' Treatments, Parenting
      Programmes, Integration of Care Models, and Pharmacotherapies. Clinical
      recommendations will be discussed. Treatment outcomes among substance using
      offenders of IPV may be improved by implementing changes in protocol that
      increase diagnostic evaluations, integrate care with evidence-based models,
      require limits to the number of offenders in a group, and require qualifications
      for clinicians who treat offenders (licensed and trained psychologists, social
      workers, and/or psychiatrists).

PMID- 27696956
TI  - Editorial.

PMID- 27696957
TI  - Effect of Ethanol Extract of Canavalia gladiata on Endurance Swimming Capacity in
      Mice.
AB  - The effects of Canavalia gladiata ethanolic extract on endurance swimming
      capacity were evaluated in a mouse model. The mice were orally administered
      distilled water (CON), hot water extract (CGW), or 80% ethanol extract (CGE). The
      swimming time to exhaustion was significantly prolonged in the CGE group. Of the
      three groups, the CGE showed the lowest blood lactate and the highest
      nonesterified fatty acid and muscle glycogen levels. These results suggest that
      the administration of CGE could improve endurance swimming capacity by enhancing
      lipid catabolism and thereby preserving glycogen stores.

PMID- 27696958
TI  - Function and application of a non-ester-hydrolyzing carboxylesterase discovered
      in tulip.
AB  - Plants have evolved secondary metabolite biosynthetic pathways of immense rich
      diversity. The genes encoding enzymes for secondary metabolite biosynthesis have
      evolved through gene duplication followed by neofunctionalization, thereby
      generating functional diversity. Emerging evidence demonstrates that some of
      those enzymes catalyze reactions entirely different from those usually catalyzed
      by other members of the same family; e.g. transacylation catalyzed by an enzyme
      similar to a hydrolytic enzyme. Tuliposide-converting enzyme (TCE), which we
      recently discovered from tulip, catalyzes the conversion of major defensive
      secondary metabolites, tuliposides, to antimicrobial tulipalins. The TCEs belong
      to the carboxylesterase family in the alpha/beta-hydrolase fold superfamily, and
      specifically catalyze intramolecular transesterification, but not hydrolysis.
      This non-ester-hydrolyzing carboxylesterase is an example of an enzyme showing
      catalytic properties that are unpredictable from its primary structure. This
      review describes the biochemical and physiological aspects of tulipalin
      biogenesis, and the diverse functions of plant carboxylesterases in the
      alpha/beta-hydrolase fold superfamily.

PMID- 27696959
TI  - Antioxidant activity of commercial food grade tannins exemplified in a wine
      model.
AB  - Although commercial tannins are widely used in foods and beverages, an improved
      understanding of the structure and composition of vegetable tannins is needed to
      promote the exploitation of agri-food by-products and waste and their
      valorisation in more sustainable industrial applications. This study aims to
      characterise the phytochemical composition and antioxidant activity of 13 food
      grade tannins using multiple analytical approaches, including spectrophotometry
      and HPLC-ECD to determine the amount of targeted polyphenolic compounds.
      Moreover, the antioxidant activity of tannins was assessed in terms of radical
      scavenging activity (DPPH* assay), reducing power (FRAP assay), and redox
      properties (cyclic voltammetry, CV). A statistical univariate and multivariate
      correlation analysis was performed on 17 parameters including tannin content
      (range: 0.71-1.62 mM), gallic acid, (+)-catechin, syringic acid and (-)
      epicatechin. The compositional profile of tannins was related to their chemical
      moiety, antioxidant activity and the botanical origin of the extracts. In
      particular, the CV signal at 500 mV was highly correlated with DPPH* value due to
      the catechol ring of flavonoids and trigalloyl moieties of gallic acid-based
      compounds. Practical examples of tannins application in winemaking are discussed.

PMID- 27696963
TI  - Rare extraskeletal Ewing's sarcoma mimicking as adenocarcinoma of the sigmoid.
AB  - INTRODUCTION: Extraskeletal Ewing's sarcoma (EES) is a rare finding in comparison
      with Ewing's sarcoma of bone and usually manifests in young patients. However,
      even in older patients, one must consider the diagnosis. PATIENTS AND METHODS: In
      this case, we describe a 52-year-old woman diagnosed with EES, mimicking as
      adenocarcinoma of the sigmoid. RESULTS: The tumor was not visualized by a multi
      slice spiral computed tomography of the abdomen and pelvis with intravenous
      contrast, and eventually the diagnosis was made by positive immunohistochemical
      staining for CD99 and by molecular testing for EWSR1 translocation. CONCLUSIONS:
      This combination of the patient's age and the localization of the tumor mimicking
      an adenocarcinoma of the sigmoid has never been described before.

PMID- 27696965
TI  - Patterns and Pathways of Competence.

PMID- 27696964
TI  - Choline and betaine ameliorate liver lipid accumulation induced by vitamin B6
      deficiency in rats.
AB  - We investigated the efficacy of supplementing the diet with choline or betaine in
      ameliorating lipid accumulation induced by vitamin B6 (B6) deficiency in rat
      liver. Male Wistar rats were fed a control, B6-deficient, choline-supplemented
      (2, 4, or 6 g choline bitartrate/kg diet) B6-deficient diet or betaine
      supplemented (1, 2, or 4 g betaine anhydrous/kg diet) B6-deficient diet for 35 d;
      all diets contained 9 g L-methionine (Met)/kg diet. Choline or betaine
      supplementation attenuated liver lipid deposition and restored plasma lipid
      profiles to control levels. These treatments restored the disruptions in Met
      metabolism and the phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio
      induced by B6 deficiency in liver microsomes. These results suggest that choline
      and betaine ameliorated liver lipid accumulation induced by B6 deficiency via
      recovery of Met metabolism and very low-density lipoprotein secretion by
      restoring the supply of PC derived from PE.

PMID- 27696972
TI  - Cefepime loaded O-carboxymethyl chitosan microspheres with sustained bactericidal
      activity and enhanced biocompatibility.
AB  - Cefepime (CFP) is a frequently used antibiotic for prevention of post-surgery
      infection. Systemic delivery of CFP in a bulk dose usually shows effective
      therapeutic effects, while cytotoxicity can also be generated. To avoid the
      drawback of systemic delivery of antibiotic, local and controlled administration
      of drug is being employed to prolong therapeutic effects and reduce cytotoxicity
      by sustaining drug release and minimizing drug exposure. In this work, CFP loaded
      polymer O-carboxymethyl chitosan (OCMC) microspheres (CFP-OCMC-MPs) were
      fabricated and their antimicrobial activity against Staphylococcus aureus as well
      as biocompatibility were evaluated. The microspheres possessed the spherical
      surface with diameter approximately 7 MUm. Fourier transforms infrared spectral
      and wide-angle X-ray diffraction analysis showed that CFP was steadily
      incorporated. The drug loading content and encapsulation efficiency of the
      microspheres were 21.4 +/- 0.5% and 42.3 +/- 0.7%, respectively. The drug release
      profiles were found to be biphasic with an initial burst release followed by a
      gradual release phase, following the Higuchi model. In addition, the CFP-OCMC-MPs
      were able to kill all the bacteria cultured in suspension within 24 h and
      exhibited long-lasting bactericidal activity as demonstrated by inhibition zone
      study. Compared to CFP, CFP-OCMC-MPs showed a milder toxicity toward osteoblast
      like cells over an 8 day period. All these results suggest that CFP-OCMC-MPs are
      endowed with sustained treatment of bacterial infection and enhanced
      biocompatibility.

PMID- 27696973
TI  - Tracheal tissue-engineering: in-vivo biocompatibility of mechanically-stripped
      allogenic rabbit trachea with autologous epithelial covering.
AB  - BACKGROUND: Successful trachea transplantation comprises the use of biocompatible
      constructs with little immune-reactivity, submucosal revascularization and
      creation of an epithelial covering. Allogenic chondrocytes might be protected
      from an overt immune-response due to physical isolation. Our aim was to evaluate
      in-vivo biocompatibility of allotracheae, stripped of their highly-immunogenic
      inner lining. Secondly, we established whether these constructs might serve as
      suitable scaffolds for autologous epithelial grafting. METHODS: Mucosa and
      submucosa of 12 rabbit donor tracheae were mechanically peeled off. Cartilage was
      covered with IntegraTM regeneration-template. Constructs were implanted within
      the recipient's lateral thoracic artery flap. Integra of 6 revascularized
      allotracheae was grafted with autologous buccal mucosa. Macroscopical,
      histological analysis and immunohistochemistry were performed. RESULTS:
      Revascularization and buccal grafting was incomplete in the first 2 circular
      constructs. To enhance blood-vessel outgrowth, the following 10 transplants were
      opened longitudinally before implantation. Integra revascularized well. Grafted
      tracheae showed satisfactory mucosa-adherence, albeit with invasion of migrating
      epithelium within the Integra-scaffold. CONCLUSIONS: Mechanically-stripped
      allotracheae exhibited beneficial biocompatibility up to two months. This
      approach might open doors in the treatment of long-segment tracheal pathologies
      of which immunosuppression is contra-indicated. Thickness of this layered
      construct limited practical feasibility of orthotopic transfer, though with
      further refinements, a clinically-useful transplant could be created.

PMID- 27696974
TI  - A tool for assessing case history and feedback skills in audiology students
      working with simulated patients.
AB  - OBJECTIVE: To develop a tool for assessing audiology students taking a case
      history and giving feedback with simulated patients (SP). DESIGN: Single
      observation, single group design. STUDY SAMPLE: Twenty-four first-year audiology
      students, five simulated patients, two clinical educators, and three evaluators.
      RESULTS: The Audiology Simulated Patient Interview Rating Scale (ASPIRS) was
      developed consisting of six items assessing specific clinical skills, non-verbal
      communication, verbal communication, interpersonal skills, interviewing skills,
      and professional practice skills. These items are applied once for taking a case
      history and again for giving feedback. The ASPIRS showed very high internal
      consistency (alpha = 0.91-0.97; mean inter-item r = 0.64-0.85) and fair-to
      moderate agreement between evaluators (29.2-54.2% exact and 79.2-100% near
      agreement; kappaweighted up to 0.60). It also showed fair-to-moderate absolute
      agreement amongst evaluators for single evaluator scores (intraclass correlation
      coefficient [ICC] r = 0.35-0.59) and substantial consistency of agreement amongst
      evaluators for three-evaluator averaged scores (ICC r = 0.62-0.81). Factor
      analysis showed the ASPIRS' 12 items fell into two components, one containing all
      feedback items and one containing all case history items. CONCLUSION: The ASPIRS
      shows promise as the first published tool for assessing audiology students taking
      a case history and giving feedback with an SP.

PMID- 27696975
TI  - A genetic features and gene interaction study for identifying the genes that
      cause hereditary spherocytosis.
AB  - OBJECTIVE: Hereditary spherocytosis (HS) is a hemolytic disorder characterized by
      the presence of spherical-shaped red blood cells on the peripheral blood smear.
      Non-dominant HS cases are due to de novo mutations of the type associated with
      dominant inheritance or recessive genes. This study is aimed to identify HS
      related biological mechanisms and predicting HS candidate genes. METHODS: We
      searched the known HS-related genes from the public databases. By analyzing the
      gene ontology (GO) and biological pathway of these genes, we extracted the
      optimal features to encode HS genes. Based on them, we predicted the HS-related
      genes from genes of whole genomes using the Random Forest classification. We used
      the gene interaction networks analysis to further identify the core regulatory
      genes that were related to HS. RESULTS: Forty-one known HS-related genes were
      found out and encoded. Three hundred and sixty-seven GO terms and ten biological
      pathway terms were identified as the optimal features for prediction. We
      subsequently predicted 150 novel HS-related genes and identified the core
      regulatory genes in the interaction network of predicted and known genes. These
      features and genes that we identified could complement the genetic features of
      HS.

PMID- 27696976
TI  - Effects of super-hard rice bread blended with black rice bran on amyloid beta
      peptide production and abrupt increase in postprandial blood glucose levels in
      mice.
AB  - Alzheimer's disease and type 2 diabetes are very serious diseases with the latter
      having been suggested to cause the former. We prepared super-hard rice bread
      blended with black rice bran (SRBBB), which contained a high amount of resistant
      starch that showed strong inhibitory activities against beta-secretase and
      acetylcholinesterase even after heating. Black rice bran showed greater beta
      secretase inhibitory activity (3.6-fold) than Koshihikari rice. The bran
      contained more oleic acid and anthocyanin, meaning that it is potentially a
      biofunctional food with a high antioxidant capacity. Furthermore, aged mice,
      which were fed a SRBBB diet for four weeks, showed lower amyloid beta 40 peptide
      in the blood than mice fed a commercial diet (p < 0.01). Additionally, their
      initial blood glucose levels (BGLs) after 12 weeks of being fed SRBBB were
      significantly lower than those in the control group. Taken together, our results
      indicate SRBBB shows promise for inhibiting not only amyloid beta production, but
      also abrupt increases in postprandial BGLs.

PMID- 27696986
TI  - Clinical Effect and Efficacy Factors of Modified Piperacillin-Tazobactam Dosing
      Regimens in Abdominal Tumor Patients with Post-Operative Pneumonia.
AB  - BACKGROUND: This study was conducted to observe the clinical efficacy of long
      term piperacillin-tazobactam (TZP) infusion and identify the factors affecting
      its curative effect against pneumonia in patients who had undergone surgery for
      abdominal tumor. METHODS: The 100 patients were divided into four clinical groups
      according to the severity of their infection: Simple pneumonia, pneumonia with
      pleural effusion, pneumonia and atelectasis, and severe pneumonia. Each group of
      patients was then divided into control and treatment groups using a completely
      random design. The control group received TZP as a regular infusion, and the
      treatment group received TZP as a long-term infusion. The cure time in the
      different groups was compared according to the administration regimen, and
      stratified analysis was carried out to identify the efficacy factors of long-term
      TZP infusion for patients with each kind of pneumonia. RESULTS: The average cure
      time for TZP differed significantly among the groups. In particular, the average
      cure times in the simple pneumonia, pneumonia with pleural effusion, pneumonia
      and atelectasis, and severe pneumonia groups were 6.800 +/- 0.342, 7.320 +/-
      0.304, 10.840 +/- 0.571, and 15.942 +/- 0.973 d (p < 0.001). In each group, the
      usage time of antibiotics in the treatment groups was significantly shorter than
      in the control group (8.87 +/- 0.64 vs. 15.95 +/- 2.02 d; p < 0.001). The cure
      times (d) for simple pneumonia and pneumonia and atelectasis were conspicuously
      lower in the treatment groups than in the control group (5.667 +/- 0.256 vs.
      7.846 +/- 0.451; p < 0.001; 9.667 +/- 1.432 vs. 11.923 +/- 0.947; p = 0.024). The
      factors associated with continuous treatment effectiveness were being male, age
      <70 years, Acute Physiology and Chronic Health Evaluation score >=17 points,
      minimum inhibitory concentration of the pathogen 8 mcg/mL, oxygenation index >200
      mm Hg, serum procalcitonin concentration >4 ng/mL, and serum albumin <25 g/L.
      CONCLUSION: Long-term TZP infusion exhibited better clinical efficacy than did
      traditional treatment in patients with pneumonia after abdominal tumor surgery.

PMID- 27696987
TI  - Assessing the reduction in infant mortality rates in Malawi over the 1990-2010
      decades.
AB  - One of the key objectives of the Millennium Development Goals (MDGs) was to
      improve the lives of infants and children, particularly the reduction of high
      infant and childhood mortality rates throughout the developing world. This paper
      examines the experiences of Malawi in tackling the problem of high infant and
      childhood mortality over recent decades, 1990-2010. We highlight the strategies
      that were used in Malawi which led to Malawi's stellar performance in achieving
      the targets set by the MDGs with reference to infant and childhood mortality. The
      data for the analysis were obtained from Demographic and Health Surveys and from
      the various censuses the country has conducted. Regression analysis using
      district as the unit of observation reveals several important factors that have
      led to the commendable declines in infant mortality. Significant factors included
      immunisation of infants as well as increasing levels of female education and the
      availability of skilled birth attendants. What Malawi's case demonstrates is that
      given a correct mix of strategies, even a poor country such as Malawi can meet
      some of the lofty targets set by the MDGs.

PMID- 27696988
TI  - Hospital support services and the impacts of outsourcing on occupational health
      and safety.
AB  - BACKGROUND: Outsourcing labor is linked to negative impacts on occupational
      health and safety (OHS). In British Columbia, Canada, provincial health care
      service providers outsource support services such as cleaners and food service
      workers (CFSWs) to external contractors. OBJECTIVES: This study investigates the
      impact of outsourcing on the occupational health safety of hospital CFSWs through
      a mixed methods approach. METHODS: Worker's compensation data for hospital CFSWs
      were analyzed by negative binomial and multiple linear regressions supplemented
      by iterative thematic analysis of telephone interviews of the same job groups.
      RESULTS: Non-significant decreases in injury rates and days lost per injury were
      observed in outsourced CFSWs post outsourcing. Significant decreases (P < 0.05)
      were observed in average costs per injury for cleaners post outsourcing.
      Outsourced workers interviewed implied instances of underreporting workplace
      injuries. CONCLUSIONS: This mixed methods study describes the impact of
      outsourcing on OHS of healthcare workers in British Columbia. Results will be
      helpful for policy-makers and workplace regulators to assess program
      effectiveness for outsourced workers.

PMID- 27696998
TI  - The Truth About Flossing.

PMID- 27697000
TI  - Gloria Parloff: Binding us together, with clear thinking and clear language, for
      a generation.

PMID- 27696999
TI  - AoAtg26, a putative sterol glucosyltransferase, is required for autophagic
      degradation of peroxisomes, mitochondria, and nuclei in the filamentous fungus
      Aspergillus oryzae.
AB  - Autophagy is a conserved process in eukaryotic cells for degradation of cellular
      proteins and organelles. In filamentous fungi, autophagic degradation of
      organelles such as peroxisomes, mitochondria, and nuclei occurs in basal cells
      after the prolonged culture, but its mechanism is not well understood. Here, we
      functionally analyzed the filamentous fungus Aspergillus oryzae AoAtg26, an
      ortholog of the sterol glucosyltransferase PpAtg26 involved in pexophagy in the
      yeast Pichia pastoris. Deletion of Aoatg26 caused a severe decrease in
      conidiation and aerial hyphae formation, which is typically observed in the
      autophagy-deficient A. oryzae strains. In addition, cup-shaped AoAtg8-positive
      membrane structures were accumulated in the Aoatg26 deletion strain, indicating
      that autophagic process is impaired. Indeed, the Aoatg26 deletion strain was
      defective in the degradation of peroxisomes, mitochondria, and nuclei. Taken
      together, AoAtg26 plays an important role for autophagic degradation of
      organelles in A. oryzae, which may physiologically contribute to the
      differentiation in filamentous fungi.

PMID- 27697002
TI  - The dangers of using 'negative durations' to estimate pre- and post-migration
      fertility.
AB  - To keep childbearing that occurs before and after migration separate from each
      other, many analysts apply a technique that uses 'negative durations' to estimate
      the childbearing risks that migrants have before they migrate. This strategy can
      lead to incorrect results and should be abandoned. In this research note, we use
      data for births and internal migration in Sweden to highlight how the two types
      of behaviour can be kept apart conceptually and analytically without use of
      'negative durations'. The procedures used can easily be generalized to any
      similarly linked pair of behaviours.

PMID- 27697003
TI  - Impact of Virginia's School-Entry Vaccine Mandate on Human Papillomavirus
      Vaccination Among 13-17-Year-Old Females.
AB  - BACKGROUND: The link between human papillomavirus (HPV) and anogenital cancers is
      well established in the literature. Many states have passed laws requiring
      funding for HPV education or vaccination. Mandatory HPV vaccination policies have
      been considered and passed in several states; yet their effectiveness has not
      been evaluated. This study sought to assess the impact of Virginia's HPV vaccine
      mandate for school-entry on HPV vaccine uptake among females aged 13-17 years.
      METHODS: Data from the National Immunization Survey-Teen for the 2008-2012 period
      were used, and 3,203 adolescent females were included in the analysis. We
      performed difference-in-differences estimation and logistic regression with a
      policy and period interaction term. Virginia was considered the treatment state,
      and South Carolina and Tennessee were the comparison states to account for
      nonpolicy factors that may have affected vaccination rates during the time period
      considered in the analysis. RESULTS: There was no evidence of an effect of
      Virginia's HPV vaccine mandate for school-entry on vaccination rates or on
      physician vaccination recommendation using either the difference-by-differences
      analysis or the policy and period interaction term in the logistic regression.
      Physician recommendation was the factor most strongly associated with vaccination
      in the Virginia-South Carolina analysis (adjusted odds ratio [aOR] = 9.33; 95%
      confidence interval [CI]: 6.11-14.3) and in the Virginia-Tennessee analysis (aOR
      = 9.33; 95% CI: 6.11-14.3). CONCLUSION: Study findings suggest that Virginia's
      HPV vaccine mandate for school-entry did not lead to a significant increase in
      HPV vaccination among adolescent females or physician recommendations. However,
      physician recommendation was the factor most strongly associated with
      vaccination.

PMID- 27697004
TI  - Intense Pulsed Light: From the Past to the Future.
AB  - BACKGROUND: For 20 years, intense pulsed light (IPL) technology has been used to
      treat various medical problems. IPL has since developed rapidly, becoming popular
      among patients worldwide. Recently, IPL has been used mainly for cosmetic
      purposes. Researchers are constantly seeking new applications of IPL to meet the
      increasing needs of patients. OBJECTIVE: This review summarizes the development
      of IPL devices, discusses the current literature on the clinical application of
      IPL to increase our understanding of IPL, and provides guidance for broadening
      its clinical applications. MATERIALS AND METHODS: We performed a systematic
      search of electronic databases, including MEDLINE and PubMed and the authors
      experience on IPL to divide IPL development into three stages: germination,
      growth, and relative maturity. RESULTS: Studies established the classical
      indications of IPL, including vascular lesions, pigmented lesions, hair growth,
      and photo rejuvenation. However, trials showed IPL has limited effects for
      complicated skin problems. Many studies explored rational combination therapies
      by IPL and laser or other cosmetic technologies. CONCLUSIONS: Based on previous
      research and the new generation of IPL devices, in the future, we predict wider
      and more effective clinical applications of IPL through the further improvement
      of IPL devices and their combined treatment.

PMID- 27697005
TI  - Photomedicine, Not Opioids, for Chronic Pain.

PMID- 27697007
TI  - Quantitative Liver Function Analysis: Volumetric T1 Mapping with Fast
      Multisection B1 Inhomogeneity Correction in Hepatocyte-specific Contrast-enhanced
      Liver MR Imaging.
AB  - Purpose To determine whether B1 inhomogeneity-corrected volumetric T1 maps of
      gadoxetic acid-enhanced liver magnetic resonance (MR) imaging are able to
      demonstrate global liver function and functional heterogeneity in patients with
      cirrhosis and to investigate their relationship with the development of hepatic
      insufficiency and decompensation. Materials and Methods This institutional review
      board-approved retrospective study with waiver of informed consent included 234
      consecutive patients who underwent gadoxetic acid-enhanced liver MR imaging,
      including B1 inhomogeneity-corrected volumetric T1 mapping. For all patients, T1
      relaxation times of the liver and liver volumes were measured on T1 maps. Liver
      T1 and functional liver volume-to-weight ratio (liver volume divided by liver T1
      and the patient's weight) were compared between Child-Pugh class A and class B
      cirrhosis. Associations between serum markers, MR parameters, hepatic
      insufficiency, and decompensation were investigated by using Cox proportional
      hazards analysis. Results Patients with Child-Pugh class B disease showed
      significantly longer liver T1 (548.2 msec +/- 257.7 vs 372.2 msec +/- 77.5, P <
      .0001) and lower kurtosis of liver T1 (29.1 +/- 39.6 vs 43.9 +/- 64.9, P = .016)
      than patients with Child-Pugh class A disease. Prolonged liver T1 (>=462 msec)
      (hazard ratio [HR], 5.9; 95% confidence interval [CI]: 1.1, 62.8) and an albumin
      level of less than 3.5 g/dL (HR, 20.7; 95% CI: 3.9, 221.9) were independently
      associated with the development of hepatic insufficiency. Functional liver volume
      to-weight ratio was associated with the development of hepatic decompensation in
      patients with Child-Pugh class A disease (HR, 0.03; 95% CI: 0.004, 0.23).
      Conclusion B1 inhomogeneity-corrected volumetric T1 mapping provided information
      on global liver function and demonstrated functional heterogeneity. In addition,
      prolonged liver T1 (>=462 msec) was associated with the development of hepatic
      insufficiency, and functional liver volume-to-weight ratio was negatively related
      with the development of decompensation in compensated cirrhosis. (c) RSNA, 2016
      Online supplemental material is available for this article.

PMID- 27697006
TI  - Meniscal Surgery: Risk of Radiographic Joint Space Narrowing Progression and
      Subsequent Knee Replacement-Data from the Osteoarthritis Initiative.
AB  - Purpose To investigate the risk of radiographic joint space narrowing (JSN)
      progression evaluated in subjects with and those without underlying
      osteoarthritis at baseline and knee replacement (KR) associated with meniscal
      surgery in subjects with and those without a reported history of preceding knee
      trauma. Materials and Methods The HIPAA-compliant protocol was approved by the
      institutional review boards of the participating centers. Written informed
      consent was obtained from all participants. Subjects who underwent meniscal
      surgery with a preceding knee trauma at baseline (n = 564) and those without (n =
      147) were drawn from the Osteoarthritis Initiative cohort (n = 4796).
      Radiographic JSN progression was evaluated by using Osteoarthritis Research
      Society International grading (progression in 1st-, 2nd-, 3rd-, 4th-, 6th-, or
      8th-year radiographic findings compared with baseline). KR was assessed up to the
      9th year of study (days passed from inclusion to KR or last follow-up). Cox
      hazard analysis was used to extract the adjusted hazard ratios (HRs) with
      adjustments for baseline age, sex, body mass index, physical activity, symptoms,
      and radiographic osteoarthritis features (Kellgren and Lawrence [KL] grade).
      Results Meniscal surgery with a history of preceding knee trauma was not
      associated with radiographic progression of JSN (adjusted HR, 0.91 [95%
      confidence interval {CI}: 0.78, 1.07]) or KR (adjusted HR, 1.02 [95% CI: 0.79,
      1.34]; P = .854). However, meniscal surgery without a history of preceding knee
      trauma was associated with radiographic progression of JSN (adjusted HR, 1.27
      [95% CI: 1.00, 1.63]) and KR (adjusted HR, 2.09 [95% CI: 1.52, 2.89]; P < .001).
      Additionally, there was a higher risk of KR in subjects with radiographic KL
      grade of less than 2 (adjusted HR, 6.97 [95% CI: 3.56, 13.64]; P < .001) at
      baseline in comparison with KL grade of at least 2 (adjusted HR, 1.76 [95% CI:
      1.22, 2.54]; P < .05). Conclusion In contrast to subjects without a reported
      preceding trauma, meniscal surgery is not independently associated with increased
      risk of radiographic JSN progression and KR in patients with a reported preceding
      trauma. (c) RSNA, 2016 Online supplemental material is available for this
      article.

PMID- 27697008
TI  - Noninvasive Assessment of Renal Fibrosis with Magnetization Transfer MR Imaging:
      Validation and Evaluation in Murine Renal Artery Stenosis.
AB  - Purpose To test the utility of magnetization transfer imaging in detecting and
      monitoring the progression of renal fibrosis in mice with unilateral renal artery
      stenosis. Materials and Methods This prospective study was approved by the
      Institutional Animal Care and Use Committee. Renal artery stenosis surgery (n =
      10) or sham surgery (n = 5) was performed, and the stenotic and contralateral
      kidneys were studied longitudinally in vivo at baseline and 2, 4, and 6 weeks
      after surgery. After a 16.4-T magnetic resonance imaging examination,
      magnetization transfer ratio was measured as an index of fibrosis (guided by
      parameters selected in preliminary phantom studies). In addition, renal volume,
      perfusion, blood flow, and oxygenation were assessed. Fibrosis was subsequently
      measured ex vivo by means of histologic analysis and hydroxyproline assay. The
      Wilcoxon rank sum or signed rank test was used for statistical comparisons
      between or within groups, and Pearson and Spearman rank correlation was used to
      compare fibrosis measured in vivo and ex vivo. Results In the stenotic kidney,
      the median magnetization transfer ratio showed progressive increases from
      baseline to 6 weeks after surgery (increases of 13.7% [P = .0006] and 21.3% [P =
      .0005] in cortex and medulla, respectively), which were accompanied by a
      progressive loss in renal volume, perfusion, blood flow, and oxygenation. The 6
      week magnetization transfer ratio map showed good correlation with fibrosis
      measured ex vivo (Pearson r = 0.9038 and Spearman rho = 0.8107 [P = .0002 vs
      trichrome staining]; r = 0.9540 and rho = 0.8821 [P < .0001 vs Sirius red
      staining]; and r = 0.8429 and rho = 0.7607 [P = .001 vs hydroxyproline assay]).
      Conclusion Magnetization transfer imaging was used successfully to measure and
      longitudinally monitor the progression of renal fibrosis in mice with unilateral
      renal artery stenosis. (c) RSNA, 2016 Online supplemental material is available
      for this article.

PMID- 27697010
TI  - Psychological and Behavioral Differences among Females Classified as Bulimic,
      Obligatory Exerciser and Normal Control.

PMID- 27697009
TI  - Intensity of Integrated Primary and Specialist Home-Based Palliative Care for
      Chronic Diseases in Northeast Italy and Its Impact on End-of-Life Hospital
      Access.
AB  - BACKGROUND: Hospital admissions at the end of life (EOL) represent an established
      indicator of poor quality of care. OBJECTIVE: To examine the impact of intensity
      of integrated primary and specialist home-based palliative care for chronic
      diseases (HPCCD) plans of care on EOL hospital access. METHODS: Retrospective
      population-based study using linked mortality, hospitalization, and home care
      data. Intensity of HPCCD was measured 90-31 days before death; outcomes were
      hospital death and prolonged hospital stay for medical reasons in the last month
      of life. Outcomes were modeled through Poisson and quartile regressions. Adults
      aged 65-84 years with at least an ordinary hospitalization and a drug treatment
      in the year before death, who died from nononcological chronic diseases in the
      Veneto Region, January 2012-December 2013, were included. RESULTS: Among 2087
      patients, 1016 (48.7%) did not receive any HPCCD homecare visit; 860 (41.2%), 152
      (7.3%), and 59 (2.8%) had <2, 2-4, and 4-7 homecare visits/week, respectively.
      Hospital death occurred for 1310 patients (62.8%) and the median hospital stay in
      the last month of life was five days (interquartile range 0-14). In multivariate
      analysis, a higher intensity of HPCCD was associated with lower rates of
      prolonged (>=14 days) EOL hospitalization and hospital death with a dose-response
      relationship. When no access to HPCCD was compared with 2-4 visits/week, adjusted
      percentage of hospital death decreased by -18.4% (95% confidence interval [CI] 
      5.4% to -29.7%) and the length of hospital stay decreased by 37.9% (95% CI 16.7%
      56.0%). CONCLUSIONS: The intensity of integrated HPCCD plans of care was
      associated with a reduction in EOL hospital stay and in hospital death.

PMID- 27697011
TI  - Helping Chronic Psychiatric Patients Adjust to Sociopolitical Changes in Poland.

PMID- 27697013
TI  - Review Essay.

PMID- 27697012
TI  - Marriage: The Whole and Its Parts.

PMID- 27697018
TI  - The hypothetical roles of arsenic in multiple sclerosis by induction of
      inflammation and aggregation of tau protein: A commentary.
AB  - Multiple sclerosis (MS) is a disease which manifests demyelination of neuronal
      cells in the brain. Despite extensive research on the mechanisms of disease
      development and progression, the exact mechanism is not elucidated yet, which has
      hampered drug development and subsequent treatment of the disease. We have
      recently shown that the serum levels of arsenic and malondialdehyde, a lipid
      peroxidation marker, are high in MS patients. In this article, we would like to
      formulate the hypothesis that arsenic may cause MS by induction of inflammation,
      degeneration, and apoptosis in neuronal cells. The induction of ROS generation in
      cells upon exposure to arsenic as a heavy metal may be involved in the
      pathogenesis of MS. Tau protein, a member of the family of microtubule-associated
      proteins, is mainly expressed in neurons and contribute to the assembly of
      neuronal microtubules network. Arsenic may affect the hyperphosphorylation and
      aggregation of tau proteins and may be involved in the cascade leading to
      deregulation of tau function associated with neurodegeneration. For validation of
      this hypothesis, studies might be conducted to evaluate the association of
      arsenic levels and tau protein levels in MS patients. Further studies might also
      focus on the trafficking along microtubules in neurons of MS patient with regard
      to hyperphosphorylation of tau protein. This hypothesis may add a new dimension
      to the understanding of MS etiology and help to design novel therapeutic agents
      against potential targets that might be discovered. If this hypothesis proves to
      be true, tau phosphorylation inhibitors can be potential candidates for MS drug
      development.

PMID- 27697020
TI  - Perioperative Considerations in Rheumatoid Arthritis Patients.
AB  - The pre-operative assessment is used to clarify issues prior to surgery that can
      change management provided by a multidisciplinary team. A high proportion of
      rheumatoid arthritis patients are elderly requiring orthopaedic surgery which
      requires further investigations, assessment of risk through functional capacity
      and several anaesthetic considerations. Rheumatoid arthritis patients often
      provide a variety of medical issues that can be found on careful and thorough pre
      assessment that can be accommodated for by the surgical and anaesthetic team,
      however aspects of holistic management is an important considerations for
      efficient and effective management.

PMID- 27697019
TI  - Identification, production and assessment of two Toxoplasma gondii recombinant
      proteins for use in a Toxoplasma IgG avidity assay.
AB  - The IgG avidity assay is an important tool in the management of suspected
      toxoplasmosis in pregnant women. This study aimed to produce new Toxoplasma
      gondii recombinant proteins and to assess their usefulness in an IgG avidity
      assay. Toxoplasma positive and negative serum samples were used, the former were
      categorized into low (LGA) and high (HGA) IgG avidity samples. Immunoblots were
      performed on 30 T. gondii cDNA clones to determine the reactivity and IgG avidity
      to the expressed proteins. Two of the clones were found to have diagnostic
      potential and were analyzed further; AG12b encoded T. gondii apical complex
      lysine methyltransferase (AKMT) protein and AG18 encoded T. gondii forkhead
      associated (FHA) domain-containing protein. The His-tagged recombinant proteins,
      rAG12b and rAG18, were expressed and tested with LGA and HGA samples using an IgG
      avidity western blot and ELISA. With the IgG avidity western blot, rAG12b
      identified 86.4% of LGA and 90.9% of HGA samples, whereas rAG18 identified 81.8%
      of both LGA and HGA samples. With the IgG avidity ELISA, rAG12b identified 86.4%
      of both LGA and HGA samples, whereas rAG18 identified 77.3% of LGA and 86.4% of
      HGA serum samples. This study showed that the recombinant antigens were able to
      differentiate low avidity and high avidity serum samples, suggesting that they
      are potential candidates for use in the Toxoplasma IgG avidity assay.

PMID- 27697021
TI  - Editorial: The microRNA 221/222 Cluster: Inaugurating a New Era in Cardiovascular
      Disease and Cancer?

PMID- 27697022
TI  - Editorial: Gut Permeability and the Microbiome: Emerging Roles in CNS Function in
      Health and Disease.

PMID- 27697023
TI  - Genetic and Epigenetic Drug Targets in Myelodysplastic Syndromes.
AB  - BACKGROUND: Myelodysplastic syndromes (MDS) represent a heterogeneous group of
      clonal disorders of hematopoietic system, characterized by genetic, epigenetic or
      microenvironmental alterations of aging hematopoietic stem cells. Pathophysiology
      of MDS comprises the suppression of normal hematopoiesis and reduced myeloid
      progenitor cells differentiation, with the main consequence of peripheral
      cytopenias and increased risk to evolution in acute myeloid leukemia (AML).
      METHOD: This review summarizes the evolving understanding of the role of genetic
      and epigenetic alterations involved in pathogenesis and current and future
      strategies for therapeutic targeting in myelodysplastic syndromes. RESULTS: In
      addition to molecular characteristics, immune and microenvironmental factors in
      bone marrow of MDS patients may further modify the MDS manifestations, its
      clinical presentation, disease course, risk of transformation to AML and
      prognosis of MDS, as well as response to therapy. Current clinical response to
      therapy approaches are exerted both by epigenetic alterations and by induction of
      apoptosis. CONCLUSION: Future treatment strategies in preclinical and clinical
      investigations are directed towards new dosing schedules of existing drugs, new
      genetic and epigenetic targets and combination of different agents, including
      hypomethylation agents and histone deacetylase inhibitors.

PMID- 27697024
TI  - Systems Toxicology: Systematic Approach to Predict Toxicity.
AB  - Drug discovery is complex and expensive. Numerous drug candidates fail late in
      clinical trials or even after being released to the market. These failures are
      not only due to commercial considerations and less optimal drug efficacies but,
      adverse reactions originating from toxic effects also constitute a major
      challenge. During the last two decades, significant advances have been made
      enabling the early prediction of toxic effects using in silico techniques.
      However, by design, these essentially statistical techniques have not taken the
      disease driving pathophysiological mechanisms into account. The complexity of
      such mechanisms in combination with their interactions with drugspecific
      properties and environmental and life-style related factors renders the task of
      predicting toxicity on a purely statistical basis which is an insurmountable
      challenge. In response to this situation, an interdisciplinary field has
      developed, referred to as systems toxicology, where the notion of a network is
      used to integrate and model different types of information to better predict drug
      toxicity. In this study, we briefly review the merits and limitations of such
      recent promising predictive approaches integrating molecular networks, chemical
      compound networks, and protein drug association networks.

PMID- 27697025
TI  - Immunological Mechanisms of Drug Hypersensitivity.
AB  - Drug hypersensitivity reactions (DHRs) are adverse drug reactions that may be
      divided into several categories; namely pharmacologic intolerance, idiosyncratic
      reactions, pseudo-allergic reactions and allergic reactions. Drug allergic
      reactions are those DHRs that are mediated by either antibodies or drug-specific
      T cells. They vary in terms of severity, time-to-onset of clinical manifestations
      and target organ. Skin is most commonly implicated in drug hypersensitivity
      reactions; however, it is now apparent that reactions targeting internal organs
      fall under the definition of drug hypersensitivity. Multiple hypotheses have been
      proposed to explain the diverse immune mechanisms involved and the heterogeneous
      clinical presentation. The discovery of human leukocyte antigen (HLA) risk
      alleles for some DHRs has provided insights in the pathogenesis of these
      reactions. In this review we summarize immune cells involved in DHRs, discuss the
      possible immunological mechanisms of DHRs, with an emphasis on the IgE-mediated
      immediate reactions and T cell-dependent delayed type reactions.

PMID- 27697027
TI  - Drug Metabolism and Pharmacokinetics of Dammarane Triterpenoids.
AB  - Dammarane triterpenoids are widely distributed in plants and are implicated in
      various bioactivities and pharmacological effects. This review focuses on
      advancements in dammarane triterpenoid metabolism, particularly drug design and
      development, including radiolabeling, absorption, distribution, metabolism,
      excretion, and pharmacokinetics, which can accurately describe the behaviors of
      dammarane triterpenoids. This review contributes to the systematic and consistent
      research and development of dammarane triterpenoids. Their structures and
      activities, radiolabel application, absorption, distribution, and pharmacokinetic
      characteristics, possible degradation pathways, metabolic enzyme induction or
      inhibitory effect, and structure-activity relationships have been described. New
      intranasal and intra-tympanic administration routes and microdialysis technology
      have also been introduced. These techniques not only improve the limits of
      dammarane triterpenoids on absorption and distribution but also facilitate the
      design and study of these compounds as potential drugs.

PMID- 27697026
TI  - Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their
      Therapeutic Potential and Clinical Trials.
AB  - BACKGROUND: A number of chemically diverse substances bind to the tubulin and
      inhibit cell proliferation by disrupting microtubule dynamics. There are four
      binding sites for the ligands binding to the tubulin; taxane/epothilone and
      laulimalide/peloruside binding ligands stabilize microtubule while vinca and
      colchicine binding site agents promote microtubule depolymerization. Most of the
      tubulin binding ligands disturb the tubulin-microtubule dynamic equilibrium but
      these may exhibit anticancer activities through different mechanisms. Taxanes and
      epothilones are widely used cytotoxic agents and are found effective against
      different types of human malignancies. However, taxanes are susceptible to pgp
      mediated multi-drug resistance, dose limiting hematopoietic toxicity and
      cumulative neurotoxicity. Vinca alkaloids are already in clinical practice, but
      ligands binding to the colchicine site are still in the different stages of
      clinical trials. OBJECTIVE: In the current review article, plausible mechanistic
      details about the interactions of ligands at the binding pocket and subsequent
      changes in the tubulin structure are described. The review article also
      illustrated different formulations of the tubulin binding agents in combination
      with other chemotherapeutic agents and their therapeutic potential against
      various human malignancies. CONCLUSION: Tubulin targeting agents emerged as one
      of the most successful anticancer drugs and a number of structurally different
      chemical compounds are in advance stages of clinical development.

PMID- 27697028
TI  - Advances in Drug Discovery: Impact of Genomics and Role of Analytical
      Instrumentation.
AB  - Drug discovery is a highly complicated, tedious and potentially rewarding
      approach associated with great risk. Pharmaceutical companies literally spend
      millions of dollars to produce a single successful drug. The drug discovery
      process also need strict compliance to the directions on manufacturing and
      testing of new drug standards before their release into market. All these
      regulations created the necessity to develop advanced approaches in drug
      discovery. The contributions of advanced technologies including high resolution
      analytical instruments, 3-D biological printing, next-generation sequencing and
      bioinformatics have made positive impact on drug discovery & development.
      Fortunately, all these advanced technologies are evolving at the right time when
      new issues are rising in drug development process. In the present review, we have
      discussed the role of genomics and advanced analytical techniques in drug
      discovery. Further, we have also discussed the significant advances in drug
      discovery as case studies.

PMID- 27697029
TI  - Fatty Acid Composition of Mangrove Wild Legume Seeds (Sesbania speciosa) in
      Southwestern India.
AB  - BACKGROUND: This study compares the composition of fatty acid methyl esters
      (FAMEs) in seeds of Sesbania speciosa (dry and mature) after processing (uncooked
      and cooked) and extraction (hot and cold). METHODS: Among PUFA, oleic, linoleic
      and linolenic acids were common to uncooked and cooked dry seeds which were high
      on cold extraction. Only two fatty acid ratios were favorable in hot extraction
      [(C14:0 + C15:0 + (C16:0 / C18:0) and C18:1 / C18:2]. RESULTS: Cold extraction
      yielded docosahexaenoic acid in uncooked as well as cooked dry seeds and all
      fatty acid ratios were nutritionally favorable. In mature seeds, lauric and
      myristic acids were high on hot extraction, while palmitic and stearic acids were
      high on cold extraction. Except for omega-6/omega-3 ratio, the rest fatty acid
      ratios in mature seeds on hot extraction were not favorable, while cold
      extraction resulted in three favorable ratios (TUFA/TSFA, TPUFA/TMUFA and omega
      6/omega-3). Three-way ANOVA on the impact of seeds, process and extraction of
      major fatty acids revealed significant difference only between extraction methods
      (p < 0.001). CONCLUSION: Overall, the cold extraction for dry as well as mature
      seeds were advantageous for essential fatty acids profile. Some of the recent
      patents are dealing with antineoplastic compounds as well as radioprotective
      drugs derived from Sesbania speciosa.

PMID- 27697030
TI  - In Vitro Study of the Antifungal Activity of Essential Oils Obtained from Mentha
      spicata, Thymus vulgaris, and Laurus nobilis.
AB  - BACKGROUND: The aim of this study was to determine the antifungal activity of the
      essential oils isolated from three aromatic plants against 13 filamentous fungal
      strains. METHODS: The major constituents of Mentha spicata, Thymus vulgaris, and
      Laurus nobilis essential oils were carvone (52.2%), linalool (78.1%), and 1,8
      cineole (45.6%), respectively. There are also some patents suggesting the use of
      essential oils as natural and safe alternatives to fungicides for plant
      protection. RESULTS: In the present work, M. spicata essential oil exhibited the
      strongest activity against all tested fungi in which Fusarium graminearum,
      F.moniliforme, and Penicillium expansum were the most sensitive to mint oil with
      lower minimal inhibitory concentration (MIC) and minimal fungicidal concentration
      (MFC) values of 2.5 MUL mL-1 (v/v). Thymus vulgaris essential oil was less active
      compared to the oil of M. spicata. Aspergillus ochraceus was the most sensitive
      strain to thyme oil with MIC and MFC values of 2.5 and 5 MUL mL-1, respectively.
      Thymus vulgaris essential oil also exhibited a moderate fungicidal effect against
      the tested fungi, except for A. niger (MFC >20 MUL-1). L. nobilis essential oil
      showed a similar antifungal activity with thyme oil in which A. parasiticus was
      the most resistant strain to this oil (MFC >20 MUL mL-1). CONCLUSION: Our
      findings suggested the use of these essential oils as alternatives to synthetic
      fungicides in order to prevent pre-and post-harvest infections and ensure product
      safety.

PMID- 27697031
TI  - Reactivation of latent HIV-1 in latently infected cells by coumarin compounds:
      Hymecromone and ScoparoneReactivation of Latent HIV-1 in Latently Infected Cells
      by Coumarin Compounds: Hymecromone and Scoparone.
AB  - BACKGROUND: Current antiretroviral therapy (ART) cannot cure HIV-1 infection due
      to the presence of latent viral reservoirs. The "shock and kill" strategy is a
      promising approach to eliminate the viral reservoir. However, there are various
      limits existing in current latency-reversing agents, searching for new activators
      are urgently needed. OBJECTIVE: The present study aimed at investigating the
      ability of hymecromone and scoparone for activating HIV-1 from latent reservoirs.
      METHODS: Jurkat T cell model of HIV-1 latently were used to evaluate the effect
      of hymecromone and scoparone. The percentage of green florescence protein
      expression as a marker for reactivation of HIV-1 promoter was measured via
      FACScan. The expression of CD25 and CD69 in human peripheral blood mononuclear
      cells was measured by flow cytometry at 72 h post-treatment with hymecromone or
      scoparone or prostratin using antibodies against CD25 and CD69. RESULTS:
      Hymecromone and scoparone can induce HIV-1 LTR reactivation in a dose and
      timedependent. We further show that hymecromone and scoparone can reactivate
      latent virus without inducing the activation of global T cells. We also found
      that scoparone acts by NF-&kgr;B signal pathway. CONCLUSION: Hymecromone and
      scoparone can effectively reactivate latent HIV-1 with low cellular toxicity,
      indicating hymecromone and scoparone might be potential drugs for HIV-1 reservoir
      eradication strategies in the future.

PMID- 27697032
TI  - Prevalence of HIV-1 Subtypes and Antiretroviral Drug Resistance Mutations in
      Nepal.
AB  - BACKGROUND: There have been very few reports of HIV-1 subtypes and drug
      resistance mutations (DRMs) from Nepal which is geographically located between
      two high-prevalence HIV-1 infection countries, China and India. OBJECTIVE: The
      aim of this study was to determine prevalence of acquired and transmitted DRMs
      and HIV-1 subtypes in Nepal. METHODS: Thirty-five HIV-1 seropositive samples from
      central region of Nepal were collected in 2011. The subjects were divided into
      two groups, antiretroviral (ARV) drug naive group (n=15) and antiretroviral
      treatment (ART) group (n=20), 90% (18/20) of them received zidovudine, lamivudine
      and nevirapine (AZT/3TC/NVP) regimen. HIV pol (protease and reverse transcriptase
      regions) nucleotide sequences were analyzed by Viroseq HIV-1 Genotyping System.
      Nearly full-length genomic (NFLG) sequences of 10 samples were performed.
      RESULTS: NFLG genotyping revealed that 80% of samples were infected with subtype
      C and 20% with recombinants (C/D/H and C/A). Phylogenetic analysis of 35 pol
      sequences from Nepal were subtype C. The prevalence of acquired DRMs to NNRTIs
      and NRTIs was 15% (3/20). DRMs to NVP, K103N and V179D, and to NRTIs were
      observed at 11.1% (2/18) and 5% (1/20), respectively. The prevalence of DRMs to
      rilpivirine for E138A/G was 5.7%. The minor protease inhibitors (PI) associated
      mutations (A71T/V and T74S) were observed in 5/35 (14.3%) subjects. CONCLUSION:
      This is the first report of NFLG HIV-1 genomic sequences and DRMs from Nepal.
      National surveillance of HIV DRMs to ARVs and molecular epidemiology study should
      be done annually for better prevention and treatment of HIV infection in Nepal.

PMID- 27697034
TI  - Playing Modular Puzzle with Adhesion/Growth-Regulatory Galectins: Design and
      Testing of a Hybrid to Unravel Structure-Activity Relationships.
AB  - The potent multifunctionality of human galectins is based on their modular
      structure in a not yet fully understood manner. A strategy to dissect the
      contributions of individual sequence stretches to lectin activity is based on
      engineering variants of the natural proteins, which are composed of novel
      combinations of distinct parts. On proof-of-principle level, we here describe the
      design of a hybrid constituted by the N-terminal tail of chimera-type galectin-3
      and the Nterminal carbohydrate recognition domain of tandem-repeat-type galectin
      8, its production, purification and its serine phosphorylation characteristic for
      galectin- 3's tail. As measured for the respective parental proteins, its binding
      to (neo)glycoproteins is specific for beta-galactosides and inhibitable by
      lactose, with KD-value closer to galectin-8 than galectin-3. Cell surface
      staining indicated similarity of the hybrid's reactivity to O-glycans and
      sensitivity for sialylation to respective properties of tandem-repeattype
      galectin-8 and its N-terminal domain. Applied as histochemical tool on tissue
      sections of murine jejunum and epididymis, intense lactose-inhibitable signals
      were recorded intracellularly, with a distribution profile akin to that of
      galectin-3. Tested as agglutinin, the hybrid was potent, excelling wild-type
      control galectins. The chimera-type design can thus serve as platform for tuning
      crosslinking activity.

PMID- 27697035
TI  - Protective Effects of Dietary Flavonoids in Diabetic Induced Retinal
      Neurodegeneration.
AB  - BACKGROUND: Diabetic retinopathy is one of the serious complications of diabetes
      and the leading cause of decreased vision and blindness worldwide.
      Neurodegeneration has been recognized as initiating factor in causing the retinal
      damage, which leads to micro-vascular damage in diabetic retinopathy. Diabetes
      induced oxidative stress is believed to be the key factor that damages neurons in
      the diabetic retina. Various therapeutic approaches for effective attenuation of
      increased oxidative stress by antioxidants have emerged. One such approach is to
      utilize dietary flavonoids, which have been found to possess powerful antioxidant
      activity. Some of the naturally occurring flavones possess anti-diabetic effects
      by enhancing insulin sensitivity and reducing plasma glucose levels in diabetic
      animal models. OBJECTIVE: Considering the importance of developing new
      antioxidant compounds and the relevance of their applications in the treatment of
      diabetes and its complications, in this review article, we discuss and highlight
      various neuroprotective mechanisms of flavonoids in the diabetic retina. RESULTS:
      Dietary supplementation of flavonoids to diabetics may reduce oxidative stress,
      which in turn might ameliorate apoptosis and the levels of neurotrophic factors
      in the diabetic retina. CONCLUSION: This approach will elucidate a novel strategy
      for preventing and treating diabetic retinoneuropathy the leading cause of low
      vision and blindness.

PMID- 27697036
TI  - Formulation and Characterization of a Ternary Inclusion Complex Containing
      Hydroxypropyl-beta-cyclodextrin and Meglumine for Solubility Enhancement of
      Poorly Water-Soluble ST-246, an Anti-Smallpox Drug.
AB  - BACKGROUND: The solubilization of poorly water-soluble drugs remains challenging.
      The purpose of this study was to design a liquid formulation that can improve the
      solubility of poorly water-soluble and weakly acidic ST-246, an anti-smallpox
      drug. METHODS: Soluble ternary cyclodextrin complexations (t-CDs) containing ST
      246, 2-hydroxypropyl-beta- cyclodextrin (HP-beta-CD) and meglumine (MEG) were
      prepared and optimized. The optimized t-CDs were further characterized using a
      scanning electron microscope (SEM), Powder X-ray Diffractometry (PXRD),
      Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy
      (FTIR) and Nuclear Magnetic Resonance Spectroscopy (NMR). RESULTS: The solubility
      of ST-246 improved dramatically from 3 ug/ml (in water, 37 degrees C) to 50 mg/ml
      in the optimized t-CDs (ST-246/MEG/HP-beta-CD, 1:2:6 weight ratio). The results
      suggested that the drug was associated with MEG through hydrogen bonds and then
      included into the hydrophobic cavity of HP-beta-CD, which might be a major factor
      for solubility improvement. To determine the exact inclusion mechanism, a Phase
      Soluble Study (PSS) was also conducted, and it indicated that a 1:1 soluble
      complex was formed between ST-246 and HP-beta-CD and that the action mechanism of
      MEG was complicated and relied on more than pH modulation. CONCLUSION: Generally,
      the optimized ternary cyclodextrin complexation might be a potential formulation
      strategy for enhancing the solubility and bioavailability of poorly water-soluble
      ST-246.

PMID- 27697033
TI  - Recombinant Antibody Fragments for Neurodegenerative Diseases.
AB  - BACKGROUND: Recombinant antibody fragments are promising alternatives to full
      length immunoglobulins and offer important advantages compared with conventional
      monoclonal antibodies: extreme specificity, higher affinity, superior stability
      and solubility, reduced immunogenicity as well as easy and inexpensive large
      scale production. OBJECTIVE: In this article we will review and discuss
      recombinant antibodies that are being evaluated for neurodegenerative diseases in
      pre-clinical models and in clinical studies and will summarize new strategies
      that are being developed to optimize their stability, specificity and potency for
      advancing their use. METHODS: Articles describing recombinant antibody fragments
      used for neurological diseases were selected (PubMed) and evaluated for their
      significance. RESULTS: Different antibody formats such as single-chain fragment
      variable (scFv), single-domain antibody fragments (VHHs or sdAbs), bispecific
      antibodies (bsAbs), intrabodies and nanobodies, are currently being studied in
      pre-clinical models of cancer as well as infectious and autoimmune diseases and
      many of them are being tested as therapeutics in clinical trials. Immunotherapy
      approaches have shown therapeutic efficacy in several animal models of
      Alzheimer's disease (AD), Parkinson disease (PD), dementia with Lewy bodies
      (DLB), frontotemporal dementia (FTD), Huntington disease (HD), transmissible
      spongiform encephalopathies (TSEs) and multiple sclerosis (MS). It has been
      demonstrated that recombinant antibody fragments may neutralize toxic extra- and
      intracellular misfolded proteins involved in the pathogenesis of AD, PD, DLB,
      FTD, HD or TSEs and may target toxic immune cells participating in the
      pathogenesis of MS. CONCLUSION: Recombinant antibody fragments represent a
      promising tool for the development of antibody-based immunotherapeutics for
      neurodegenerative diseases.

PMID- 27697037
TI  - Physicochemical, Pharmacodynamic and Pharmacokinetic Characterization of Soluplus
      Stabilized Nanosuspension of Tacrolimus.
AB  - BACKGROUND: Tacrolimus, an immunosuppressive drug has a variable pharmacokinetic
      and poor oral bioavailability due to poor solubility. The aim of the present
      study was enhancing the solubility and oral bioavailability of this drug.
      METHODS: Tacrolimus nanoparticles were prepared by precipitation anti-solvent
      evaporation method. The effect of different parameters including: surfactant
      type, solvent to nonsolvent ratio and drug to surfactant ratio were studied on
      the particle size, saturated solubility and dissolution rate of the drug. The
      solid state characterization was done by fourier transform infrared spectroscopy
      (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD)
      and scanning electron microscopy. The untreated drug (5 mg.kg-1day-1),
      nanoparticles or physical mixture of the drug and the stabilizers were
      administered to rats and blood levels of tacrolimus were assessed by
      electrochemiluminence method. The oral drug administration was done for 10 days
      then the changes in white blood cells (WBC) and percent lymphocyte count were
      determined before drug administration, 5 and 10 days after drug administration.
      RESULTS: FTIR spectroscopy showed no interaction between the drug and
      stabilizers. XRPD and DSC studies indicated the amorphous state of the drug in
      nanosuspensions. The solvent to nonsolvent ratio of 1:20 and drug to surfactant
      ratio of 1:3 enhanced 185 fold the saturated solubility and 17 fold dissolution
      rate of the drug. In vivo studies also showed tacrolimus nanoparticles
      significantly reduced the lymphocyte and WBC, enhanced 66 and 34 fold the AUC0-24
      and Cmax of the drug, respectively. CONCLUSION: The precipitation anti-solvent
      evaporation is a nano-crystalization technique which showed to be an effective
      approach for enhancing water solubility and bioavailability of tacrolimus.

PMID- 27697038
TI  - Bruton Kinase Inhibitors in Chronic Lymphocytic Leukemia.
AB  - Abnormality of the B-cell receptor (BCR) signaling is correlated to origin of
      many B-cell malignancies. Bruton's tyrosine kinase (BTK), is described as a
      possible target in a many B-cell neoplasms. Ibrutinib is the most used inhibitor
      of BTK and has great tolerability and efficacy in chronic lymphocytic leukemia.
      This review summarizes results with ibrutinib in clinical trials and novel BTK
      inhibitors of interest.

PMID- 27697039
TI  - Therapeutic Effects of Rivastigmine and Alfa-Lipoic Acid Combination in the
      Charles Bonnet Syndrome: Electroencephalography Correlates.
AB  - BACKGROUND: Charles Bonnet Syndrome (CBS) is a rare clinical condition which is
      characterized by complex hallucinations in visually impaired patients. The
      pathophysiology of this disorder remains largely unknown, and there is still no
      proven treatment for this disease. In our study, we aimed to investigate the
      neural activity through Electroencephalography (EEG) power and evaluate the
      effect of rivastigmine in combination with alpha-lipoic acid on hallucination in
      two CBS patients with diabetic retinopathy. METHODS: EEG data was recorded with
      standard routine EEG protocols for both patients in our electrophysiological
      research laboratory (REMER Clinical Electrophysiology and Neuromodulation
      Research and Application Laboratory) with Brain Vision Recorder (Brainproduct,
      Munich, Germany). All spectral analyses were processed by BrainVision Analyzer 2
      (Brainproduct, Munich, Germany, 2.0.4 Version) in 128 Hz sample rates and the EEG
      recording and analysis was performed before the administration of rivastigmine
      (4.5 mg/daily and five patch daily for the first and second patients,
      respectively) in combination with alpha-lipoic acid (600 mg/daily) for both
      patients while they were not hallucinated during the time period recordings.
      Based on our measurement protocol, we have compared the patients in the study
      group with the three control subjects who were found to be normal except of
      visual disturbances secondary to significant diabetic retinopathy. RESULTS:
      Highest theta power values were found in right occipital and left temporo
      parietal regions for first and second CBS patients, respectively. Additionally,
      power spectra were lower in two cases as compared to their control groups in the
      alpha band for all electrodes. We have also shown that acid rivastigmine in
      combination with alpha-lipoic exerted significant anti-hallucinatory efficiency.
      CONCLUSION: Our present findings could support the hypothesis that increased
      activation of specific areas in the source monitoring system plays an important
      role in the pathogenesis of CBS. In addition, rivastigmine in combination with
      alpha-lipoic acid could be a new valuable option for CBS patients.

PMID- 27697041
TI  - A Comprehensive Review on the Biological and Pharmacological Activities of
      Rhodanine Based Compounds for Research and Development of Drugs.
AB  - At present, diseases resulting from various reasons have been causing deadly
      fears to humans and previously incogitable losses to health. Meanwhile, the
      patient compliance has been weakening because of drug resistance and serious drug
      adverse effects. There is therefore an urgent need for the development of novel
      structural agents. Rhodanine derivatives have exhibited wide biological
      activities, as well as significant industrial applications, which suggests that
      rhodanine heterocycle represents a key structural motif in heterocyclic chemistry
      and occupies a prominent position in drug discovery. Here, we review some deadly
      defects of clinical medicines to the therapy of diseases and important advances
      on rhodanine derivatives in drug researches (e.g. as anti-diabetic, anti-viral,
      antiinflammatory, anti-microbial, anti-tumor agents and inhibitors for Alzheimer
      Disease), indicating that rhodanine heterocycle could be used as a significant
      pharmacophore to develop novel pharmacological active molecules. It is believed
      that the review is of importance for new ideas in the development of and rational
      designs of rhodanine-based drugs.

PMID- 27697042
TI  - Animal Venom Peptides: Potential for New Antimicrobial Agents.
AB  - Microbial infections affect people worldwide, causing diseases with significant
      impact on public health, indicating the need for research and development of new
      antimicrobial agents. Animal venoms represent a vast and largely unexploited
      source of biologically active molecules with attractive candidates for the
      development of novel therapeutics. Venoms consist of complex mixtures of
      molecules, including antimicrobial peptides (AMPs). Since the discovery of AMPs,
      they have been studied as promising new antimicrobial drugs. Amongst the
      remarkable sources of AMPs with known antimicrobial activities are ants, bees,
      centipedes, cone snails, scorpions, snakes, spiders, and wasps. The antimicrobial
      tests against bacteria, protozoans, fungi and viruses using 170 different
      peptides isolated directly from crude venoms or cDNA libraries of venom glands
      are listed and discussed in this review, as well as hemolytic ativity. The
      potential of venoms as source of new compounds, including AMPs, is extensively
      discussed. Currently, there are six FDA-approved drugs and many others are
      undergoing preclinical and clinical trials. The search for antimicrobial
      "weapons" makes the AMPs from venoms promising candidates.

PMID- 27697043
TI  - The Antibacterial Activity of Metal Complexes Containing 1,10- phenanthroline:
      Potential as Alternative Therapeutics in the Era of Antibiotic Resistance.
AB  - The "antibiotic era", characterized by the overuse and misuse of antibiotics,
      over the last half-century has culminated in the present critical "era of
      resistance". The treatment of bacterial infections is challenging because of a
      decline in the current arsenal of useful antibiotics and the slow rate of new
      drug development. The discovery of a new gene (mcr-1) in 2015, which enables
      bacteria to be highly resistant to polymyxins (such as colistin), the last line
      of antibiotic defence left, heralds a new level of concern as this gene is
      susceptible to horizontal gene transfer, with alarming potential to be spread
      between different bacterial populations, suggesting that the progression from
      "extensive drug resistance" to "pan-drug resistance" may be inevitable. Clearly
      there is a need for the development of novel classes of anti-bacterial agents
      capable of killing bacteria through mechanisms that are different to those of the
      known classes of antibiotics. 1,10-phenanthroline (phen) is a heterocyclic
      organic compound which exerts in vitro antimicrobial activity against a broad
      spectrum of bacteria. The antimicrobial activity of phen can be significantly
      modulated by modifying its structure. The development of metal-phen complexes
      offers the medicinal chemist an opportunity to expand such structural diversity
      by controlling the geometry and varying the oxidation states of the metal centre,
      with the inclusion of appropriate auxiliary ligands in the structure, offering
      the opportunity to target different biochemical pathways in bacteria. In this
      review, we summarize what is currently known about the antibacterial capability
      of metal-phen complexes and their mechanisms of action.

PMID- 27697044
TI  - Challenges and Persistent Questions in the Treatment of Trichomoniasis.
AB  - Trichomoniasis is a sexually transmitted disease (STD) caused by infection with
      the protozoan parasite Trichomonas vaginalis. It is considered the most prevalent
      non-viral sexually transmitted disease worldwide. Recently, the infection has
      been associated with adverse outcomes of pregnancy and increased risks of HIV
      acquisition and transmission, as well as an association with cervical and
      prostate cancers. The consequences of trichomoniasis are likely much greater than
      previously recognized, both at the individual and the community level. Since many
      cases are asymptomatic, and the most common approach used for diagnosis (wet
      mount) is also one of the least sensitive, millions of T. vaginalis infections
      remain undiagnosed and therefore untreated. The purpose of this review is to
      address what is known about the treatment of T. vaginalis infections and what
      additional approaches could be pursued. The increasing recognition of the
      potential public health implications of trichomoniasis has resulted in greater
      attention to improving effectiveness of the interventions for affected
      individuals. Currently, treatment relies almost solely on one class of drugs, the
      5- nitroimidazoles, which causes concern should widespread drug resistance arise.
      There are also concerns regarding which 5-nitroimidazole to use as not all of
      them are active against T. vaginalis. Finally, new therapeutic targets and active
      compounds with treatment potential are considered.

PMID- 27697045
TI  - Bacterial Labionin-Containing Peptides and Sactibiotics: Unusual Types of
      Antimicrobial Peptides with Potential Use in Clinical Settings (a Review).
AB  - One of the biggest challenges faced presently by clinicians is the emergence of
      multidrug -resistant pathogens that can infect humans and animals. To control the
      infections caused by such pathogens the development of new drugs is required.
      Bacteria are a rich source of ribosomally -synthesized antimicrobial peptides
      known as bacteriocins, which are characterized by the presence of a self-defense
      immunity system. Labionin-containing lantibiotics and sactibiotics are
      posttranslationally modified bacteriocins with peculiar features. Labionin
      containing peptides belong to subclass Ic lantibiotics in which the carbacyclic
      triamino triacid labionin, a structural variant of lanthionine, and a methyl
      substitute labionin derivative are found, giving the molecule a labyrinthine
      structure. Sactibiotics are circular or linear peptides belonging to a distinct
      bacteriocin class (class V) which is characterized by the presence of cross
      linkages formed by the thiol group of cysteine residues and the alpha-carbon of
      acceptor amino acids. A few examples of these bacteriocins have been described in
      the literature to date, although putative gene clusters with the potential to
      encode such peptides can be found in the genome of many bacterial species. Some
      peptides already under study exhibit potential biotechnological applications
      because of their remarkable antibacterial or antiviral activities, as well as
      their analgesic activity. Therefore, in this review, the main findings concerning
      these peptides will be addressed and discussed, with an emphasis on their
      potential use in clinical settings.

PMID- 27697047
TI  - Hybrid Compounds as Anti-infective Agents.
AB  - Hybrid drugs are multi-target chimeric chemicals combining two or more drugs or
      pharmacophores covalently linked in a single molecule. In the field of anti
      infective agents, they have been proposed as a possible solution to drug
      resistance issues, presumably having a broader spectrum of activity and less
      probability of eliciting high level resistance linked to single gene product.
      Although less frequently explored, they could also be useful in the treatment of
      frequently occurring co-infections. Here, we overview recent advances in the
      field of hybrid antimicrobials. Furthermore, we discuss some cutting-edge
      approaches to face the development of designed multi-target agents in the era of
      omics and big data, namely analysis of gene signatures and multitask QSAR models.

PMID- 27697046
TI  - Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections.
AB  - Despite the fact that bacterial infections are one of the leading causes of death
      worldwide and that mortality rates are increasing at alarming rates, no new
      antibiotics have been produced by the pharmaceutical industry in more than a
      decade. The situation is so dire that the World Health Organization warned that
      we may enter a "post-antibiotic era" within this century; accordingly, bacteria
      resistant against all known antibiotics are becoming common and already producing
      untreatable infections. Although several novel approaches to combat bacterial
      infections have been proposed, they have yet to be implemented in clinical
      practice. Hence, we propose that a more plausible and faster approach is the
      utilization of drugs originally developed for other purposes besides
      antimicrobial activity. Among these are some anticancer molecules proven
      effective in vitro for eliminating recalcitrant, multidrug tolerant bacteria;
      some of which also protect animals from infections and recently are undergoing
      clinical trials. In this review, we highlight the similarities between cancer
      cells/tumors and bacterial infections, and present evidence that supports the
      utilization of some anticancer drugs, including 5-fluorouracil (5-FU), gallium
      (Ga) compounds, and mitomycin C, as antibacterials. Each of these drugs has some
      promising properties such as broad activity (all three compounds), dual
      antibiotic and antivirulence properties (5-FU), efficacy against multidrug
      resistant strains (Ga), and the ability to kill metabolically dormant persister
      cells which cause chronic infections (mitomycin C).

PMID- 27697048
TI  - Hybrid Compounds as Direct Multitarget Ligands: A Review.
AB  - Molecular Hybridization is an approach in rational drug design where new chemical
      entities are obtained by combining two or more pharmacophoric units from
      different bioactive compounds into a single molecule. Through this approach,
      medicinal chemists hope that the new hybrid derivative presents: better affinity
      and efficacy when compared to the parent drugs; a modified selectivity profile
      with improvement over pharmacokinetic and pharmacodynamic restrictions; dual or
      multiple modes of action; reduction of undesirable side effects; decreases in
      drug-drug interactions; reduced emergence or spread of drug resistance in
      microorganisms and protozoans; and lower cost. The approach has been successfully
      used by many research groups around the world and has had very promising results
      with diseases having multifactorial profiles, like Alzheimer's, Parkinson's
      disease, cancer, inflammation, and hypertension among others. The purpose of this
      paper is to conduct an updated review of molecular hybridization and multitarget
      profiling (a rational drug design approach), and its applications to the design
      and discovery of novel hybrid compounds with anti-inflammatory, antimicrobial,
      anticancer and antiprotozoal (leishmaniasis, malaria, and schistosomiasis)
      activities over the last six years.

PMID- 27697049
TI  - Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and
      Anti-inflammatory Area.
AB  - Macrolides, polyketide natural products, and their 15-membered semi-synthetic
      derivatives are composed of substituted macrocyclic lactone ring and used
      primarily as potent antibiotics. Recently their usefulness was extended to
      antimalarial and anti-inflammatory area. Hybrid macrolides presented in this
      article are the next generation semi-synthetic compounds that combine
      pharmacophores from antibacterial, antimalarial and anti-inflammatory area with
      14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with
      sulphonamides showed improved activity against resistant streptococci while
      quinolone conjugates demonstrated full coverage of respiratory pathogens
      including macrolide resistant strains and their efficacy was confirmed in mouse
      pneumonia model. Antimalarial macrolide hybrids, mainly involving
      (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine
      resistant strains, favourable pharmacokinetics, promising in vivo efficacy as
      well as encouraging developmental potential. Anti-inflammatory hybrids were
      obtained by combining macrolides with corticosteroid and non-steroidal anti
      inflammatory drugs. They were found active in in vivo animal models of locally
      induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis
      and demonstrated improved safety over parent steroid drugs. Overall, macrolide
      hybrids possess significant potential to be developed as potent novel medicines
      in therapeutic areas of utmost pharmaceutical interest.

PMID- 27697050
TI  - Hybrid Compounds as Multitarget Directed Anticancer Agents.
AB  - Cancer is a multifactorial disease including interactions of complex genetic and
      environmental factors. Clinical efficacy of anticancer chemotherapies is hampered
      by various factors including multidrug resistance (MDR). There is a strong need
      to discover more potent novel cancer drugs to kill cancer cells selectively. The
      recent new strategy for cancer treatment involves the design and synthesis of
      hybrid compounds as multitargeted anticancer agents. In this review, we focus on
      studies using hybrid compounds which were designed and synthesized from two or
      more different bioactive moieties conjugating them into a single hybrid drug.
      Hybrid compounds having more than a single target have been considered as more
      efficient and potent anticancer agents, since it is almost impossible to destroy
      cancer cells with a single target. Hybrid compounds overcome many disadvantages
      of single cancer drugs such as low solubility, adverse effects, and multi drug
      resistance. We have compiled the data of recent studies using the new hybrid
      anticancer drugs in cancer treatment. Thus, the design, synthesis and clinical
      trials of new hybrid compounds should be continued and supported in future.
      Results of recent studies have proved that they have a great potential to be used
      as novel anticancer drugs.

PMID- 27697051
TI  - Hybrid Drugs as Potential Combatants Against Drug-Resistant Microbes: A Review.
AB  - Antimicrobial resistance to drugs is a serious threat to public health. Different
      strategies have been adopted to deal with antimicrobial resistance to known
      drugs, one such strategy is the use of drug hybrids; this is a promising strategy
      to address the growing problem of drug resistance. The present review covers the
      very recent examples of combining (hybrid) two standard drugs in a single
      molecule for combating antibiotic-resistant microorganisms, and to present
      evidence supporting that drug hybrids are the urgent and practical solution to
      stop or slow down the spread of drug resistance. In addition, this review
      provides a literature overview of antimicrobial hybrids of standard drugs and
      their impact on antimicrobial resistance, covering publications between 2015 and
      2016.

PMID- 27697052
TI  - Novel Multitarget Hybrid Compounds for the Treatment of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the most prevalent among the aging diseases known as
      neurodegenerative disorders. Drug design programs over the last two decades were
      mainly based on the cholinergic, the amyloid or the tau hypothesis. However, none
      of the new drugs have a real impact on the outcome of the disease. The complex
      nature of AD has led to new approaches for drug development programs, the
      multitarget drug design hypothesis. Based on this hypothesis, the generation of
      multitarget hybrid compounds from previously known active molecules has been one
      of the most widely used to obtain new candidates for the future treatment of AD.
      Here, we summarize recent developments based on the hybridization hypothesis to
      obtain a potential clinical candidate for AD.

PMID- 27697053
TI  - Nitric Oxide-NASIDS Donor Prodrugs as Hybrid Safe Anti-inflammatory Agents.
AB  - Selective inhibition of cyclooxygenase-2 (COX-2) isozyme afforded a useful drug
      design concept that resulted in the development of effective anti-inflammatory
      drugs that are devoid of adverse side effects, in particular gastrointestinal
      irritation, ulcerogenicity and renal toxicity attributed to inhibition of the
      cytoprotective cyclooxygenase-1 (COX-1) isozyme. Unfortunately, some selective
      COX-2 inhibitory drugs such as rofecoxib and valdecoxib are believed to be
      responsible for cardiovascular complications. Nitric oxide (NO) is an effective
      vasodilator that also inhibits platelet aggregation. Therefore hybrid NSAIDs
      containing NO-donor moieties have been developed to obtain effective treatment of
      inflammation with reduced GI and cardiovascular side effects. Here we review some
      of the most promising recent advances in NO-NAISDs donor drug development and
      summarizes medicinal chemistry efforts in search for new NO-NSAIDs prodrugs in an
      attempt to pave the way for further development in this promising area of
      research.

PMID- 27697054
TI  - Novel Hybrid Anticonvulsants Derived from Pyrrolidine-2,5-dione Scaffold with
      Broad Spectrum of Activity in the Preclinical Studies.
AB  - The multifunctional ligands application is an emerging approach in drug delivery,
      mainly in the treatment of diseases with complex pathology, such as Alzheimer's,
      cancer, and epilepsy. Using this method many biomolecules with different
      properties are combined to form a single unit that can provide a complex broad
      spectrum activity. Thus, a new type of hybrid anticonvulsants based on the
      pyrrolidine-2,5-dione frame are detailed with the aim of acquiring more effective
      antiepileptic drugs (AED) that could suppress various human convulsions. These
      hybrid molecules attach to the chemical particles of clinically relevant AEDs
      such as ethosuximide, levetiracetam, and lacosamide. As a result of this
      hybridization process the compounds obtained were effective in three most
      important animal epilepsy models, namely the maximal electroshock seizure (MES)
      test, the subcutaneous pentylenetetrazole (scPTZ) test, and the six-Hertz (6 Hz)
      model in mice. These substances displayed wider spectrum of protection, more
      potent efficacy, and better safety profile than the aforementioned AEDs. Several
      compounds were also active in the formalin model of persistent pain in mice. The
      in vitro ligand binding studies have proved that the most conceivable molecular
      mechanism of anticonvulsant and antinociceptive action was the influence on the
      neuronal voltage-sensitive sodium and L-type calcium channels.

PMID- 27697055
TI  - Multitarget Tacrine Hybrids with Neuroprotective Properties to Confront
      Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Several
      hallmarks such as beta-amyloid (Abeta) aggregation underlying amyloid plaque
      formation, tau-hyperphosphorylation leading to production of neurofibrillary
      tangles, and decline in the number of cholinergic neurons appear to be
      fundamental in the pathophysiology of the disease. Other evidence points also to
      the involvement of oxidative stress, biometal dyshomeostasis, inflammation, and
      cell cycle regulatory failure. Taking into account such premises, many attractive
      targets for the development of anti-AD drugs have emerged. Specifically, the
      multifactorial nature of AD calls for multi-target-directed ligands (MTDLs) which
      can be beneficial by providing interactions with multiple targets. Tacrine (THA),
      the first clinically effective acetylcholinesterase inhibitor, was approved for
      the treatment of mild to moderate AD. Unfortunately, frequent adverse effects
      including peripheral cholinergic effects and hepatotoxicity limited its
      therapeutic potential. Based on the numerous biological systems involved in AD
      progression, this review covers THA-incorporated hybrids possessing a
      neuroprotective profile. In particular, it focuses on THA hybrids capable of
      scavenging reactive oxygen species (ROS), and derivatives which reduce the
      formation of Abeta-plaques either directly by confronting the Abeta1-42
      selfaggregation process or indirectly by inhibiting the BACE-1 enzyme or AChE
      induced Abeta1-40 aggregation. Particular interest is also addressed to THA
      hybrids with suppressed hepatotoxicity.

PMID- 27697040
TI  - Pharmacological Tools to Activate Microglia and their Possible use to Study
      Neural Network Patho-physiology.
AB  - BACKGROUND: Microglia are the resident immunocompetent cells of the CNS and also
      constitute a unique cell type that contributes to neural network homeostasis and
      function. Understanding microglia cell-signaling not only will reveal their
      diverse functions but also will help to identify pharmacological and non
      pharmacological tools to modulate the activity of these cells. METHODS: We
      undertook a search of bibliographic databases for peer-reviewed research
      literature to identify microglial activators and their cell-specificity. We also
      looked for their effects on neural network function and dysfunction. RESULTS: We
      identified several pharmacological targets to modulate microglial function, which
      are more or less specific (with the proper control experiments). We also
      identified pharmacological targets that would require the development of new
      potent and specific modulators. We identified a wealth of evidence about the
      participation of microglia in neural network function and their alterations in
      pathological conditions. CONCLUSION: The identification of specific microglia
      activating signals provides experimental tools to modulate the activity of this
      heterogeneous cell type in order to evaluate its impact on other components of
      the nervous system, and it also helps to identify therapeutic approaches to ease
      some pathological conditions related to microglial dysfunction.

PMID- 27697056
TI  - Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target
      Drugs: Lead Generation Approaches.
AB  - Finding high quality beginning compounds is a critical job at the start of the
      lead generation stage for multi-target drug discovery (MTDD). Designing hybrid
      compounds as selective multitarget chemical entity is a challenge, opportunity,
      and new idea to better act against specific multiple targets. One hybrid molecule
      is formed by two (or more) pharmacophore group's participation. So, these new
      compounds often exhibit two or more activities going about as multi-target drugs
      (mtdrugs) and may have superior safety or efficacy. Application of integrating a
      range of information and sophisticated new in silico, bioinformatics, structural
      biology, pharmacogenomics methods may be useful to discover/design, and synthesis
      of the new hybrid molecules. In this regard, many rational and screening
      approaches have followed by medicinal chemists for the lead generation in MTDD.
      Here, we review some popular lead generation approaches that have been used for
      designing multiple ligands (DMLs). This paper focuses on dual- acting chemical
      entities that incorporate a part of two drugs or bioactive compounds to compose
      hybrid molecules. Also, it presents some of key concepts and
      limitations/strengths of lead generation methods by comparing combination
      framework method with screening approaches. Besides, a number of examples to
      represent applications of hybrid molecules in the drug discovery are included.

PMID- 27697057
TI  - Multi-Target Directed Indole Based Hybrid Molecules in Cancer Therapy : An Up-To
      Date Evidence-Based Review.
AB  - Cancer is a multifactorial disease and most of its types still remain incurable,
      in spite of enormous efforts to explicate various tumor pathophysiology. The anti
      cancer drug discovery paradigm "one-compound-one-target" has failed and
      subsequently shifted to two-drug cocktail and recently the "multi-target
      approach" in order to design and develop agents able to act simultaneously on
      multiple intracellular constituents and signaling pathways. Novel hybrid
      compounds are now designed by incorporating two covalently linked independently
      acting pharmacores, each efficient at combating cancer. They can deliver
      synergistic effects from the dual action of both independently acting moieties by
      interacting with multiple targets. These composite molecules are also less prone
      to drug resistance, leading to an improved pharmacological potency than each
      individual moiety. As indole nucleus is a central component of many natural and
      synthetic molecules with extensive biological activity, this review incorporates
      a variety of such hybrid compounds with indole moiety as one of the active units,
      where better therapeutic effect has been successfully achieved, by either
      simultaneous or sequential action of individual functional pharmacore. The
      current limitations and challenges encountered in the development of these hybrid
      agents are also discussed.

PMID- 27697058
TI  - Multi-targeting Andrographolide and its Natural Analogs as Potential Therapeutic
      Agents.
AB  - Andrographis paniculata (A. paniculata) is a medicinal plant used in the Indian
      and Chinese traditional medicinal systems for its various beneficial properties
      of therapeutics. This is due to the presence of a diterpene lactone called
      'andrographolide'. Several biological activities like antiinflammatory,
      antitumour, anti-hyperglycaemic, anti-fertility, antiviral, cardio protective and
      hepatoprotective properties are attributed to andrographolide and its natural
      analogs. The studies have shown that not only this diterpene lactone
      (andrographolide), but also other related terpenoid analogs from A. paniculata
      could be exploited for disease prevention due to their structural similarity with
      diverse pharmacological activities. Several scientific groups are trying to
      unveil the underlying mechanisms involved in these biological actions brough aout
      by andrographolide and its analogs. This review aims at giving an overview on the
      therapeutical and/or pharmacological activities of andrographolide and its
      derivatives and also exemplify the underlying mechanisms involved.

PMID- 27697059
TI  - Novel Structural Hybrids on the Base of Benzofuroxans and Furoxans. Mini-Review.
AB  - Hybrid drug strategy is based on the combination of two or more pharmacophores
      into a new chemical entity to improve the properties of the original compounds or
      to obtain double action of resulting molecule. Hybrid molecules, comprised of
      some pharmacophore and nitric oxide (NO) donor moiety, constitute one of the more
      promising approaches for the design of drugs. Furoxans and benzofuroxans are
      considered NO releasing prodrugs and are of great interest for researchers. In
      this review we will focus on furoxan and benzofuroxan hybrids described in
      literature during the last years (from 2005 to 2016).

PMID- 27697060
TI  - Prediction of Anti-Diabetic Drugs as Dual Inhibitors Against Acetylcholinesterase
      and Beta-Secretase: A Neuroinformatics Study.
AB  - An increasing number of research evidences indicate linkage between type 2
      diabetes mellitus (T2DM) and Alzheimer's disease (AD); the two most common
      diseases of aging. In addition, T2DM and AD also share some common
      pathophysiological features. Therefore, dual therapy that targets both the
      diseases can be regarded as a beneficial approach. Acetylcholinesterase (AChE)
      and beta-secretase (BACE) have been considered as potential therapeutic targets
      for AD. Accordingly, the piece of work presented here describes the binding of
      anti-diabetic drugs (Jardiance, Suiny and Nesina) with AChE and BACE so as to
      further investigate connecting bridges concerning the treatment of these two
      diseases. We have used "Autodock 4.2" for docking experiments. Both, hydrogen
      bond and hydrophobic interactions were found to be involved in the proper
      positioning of these diabetic drugs within the catalytic site (CAS) of AChE and
      BACE enzymes to permit docking. Free energy of binding (DeltaG) for 'Jardiance
      AChE', 'uiny-AChE' and 'Nesina-AChE' CAS interactions were found to be -9.21, 
      7.32 and -10.66 kcal/mol, respectively; while for 'Jardiance-BACE', 'Suiny -BACE'
      and 'Nesina-BACE' CAS interactions the same were determined to be -8.91, -8.58
      and -10.40 kcal/mol, respectively. Hence, these diabetic drugs might act as
      potent dual inhibitors for the treatment of diabetes-associated neurological
      disorders. Consequently, the results described herein may form the basis of
      future dual therapy against the same.

PMID- 27697061
TI  - Therapeutic Noninvasive Brain Stimulation in Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a looming public health crisis that currently lacks
      an effective treatment. Noninvasive Brain Stimulation (NBS), particularly
      transcranial magnetic stimulation (TMS) and transcranial direct current
      stimulation (tDCS), offers a promising alternative approach to pharmacological
      interventions for an increasing number of neurological and psychiatric
      conditions. The aim of this review is summarize data from therapeutic trials of
      NBS in AD and other dementing illnesses. Despite the potential of NBS, there is
      limited theoretical framework and a lack of guidelines for its applications to
      AD. Several published clinical trials failed to report key parameters of the
      interventions thus limiting the utility of the study to assess efficacy and
      safety. Our review concludes with some suggestions for future studies aimed to
      advance research into NBS as a potential treatment for the symptoms and
      disabilities caused by AD and to enable comparison of results across trials.
      Ultimately, appropriately powered, and controlled, multi-site randomized clinical
      trials will be needed to evaluate the therapeutic potential of NBS in AD.

PMID- 27697062
TI  - Beyond Acetylcholinesterase Inhibitors: Novel Cholinergic Treatments for
      Alzheimer's Disease.
AB  - The major components of the cholinergic receptor system of the human brain
      include projections from the basal forebrain nuclei, and utilize the two types of
      receptors that they synapse on, nicotinic and muscarinic acetylcholine receptors.
      With the widespread cortical and subcortical projections of the basal forebrain,
      activity of these two receptor systems provide modulation of neurotransmitter
      activity underlying normal cognitive processes, such as attention, episodic
      memory, and working memory. Alzheimer's disease (AD) targets and damages
      cholinergic neurons in the basal forebrain, and as these projections are lost,
      cognitive performance progressively declines. Currently, the most widely
      prescribed treatment for AD is acetylcholinesterase inhibitor medications, which
      work by partially blocking the degradation of acetylcholine in the synapse and
      enabling more of the neurotransmitter to reach and activate cholinergic
      receptors. However since these medications have limited effectiveness, alternate
      treatments that focus on augmenting the activity of the receptors themselves,
      independent of acetylcholinesterase inhibition, are being explored. This review
      will discuss: 1) the role of the cholinergic system in modulating cognition, 2)
      novel cholinergic treatment strategies for AD-related cognitive decline, in
      particular treatments intended to increase cholinergic system activity by
      selectively targeting muscarinic and nicotinic acetylcholinergic receptors to
      improve cognitive performance, 3) risks, and additional considerations for
      cholinergic cognitive treatments for AD.

PMID- 27697065
TI  - Gender Disparity in Lipid Target Achievements in High and Very High
      Atherosclerotic Cardiovascular Disease Risk Patients in the Arabian Gulf.
AB  - BACKGROUND: Few studies assessed gender disparity in lipid goal attainment in the
      Arabian Gulf. Hence, we estimated gender gaps in lipid target achievements among
      patients at high and very high atherosclerotic cardiovascular disease (ASCVD)
      risk in the Centralized Pan-Middle East Survey on the undertreatment of
      hypercholesterolemia (CEPHEUS). METHODS: The study (conducted between November
      22, 2009 and July 7, 2010) included 4,384 patients (&#8805;18 years) on lipid
      lowering drugs at high and very ASCVD risk status from outpatient clinics of 177
      specialists and primary care physicians in 6 Arabian Gulf countries. RESULTS: The
      overall mean age was 57+/-11 years and 40% (n=1763) were women. Women were more
      likely to have diabetes mellitus (84 vs 71%; p <0.001) and metabolic syndrome (49
      vs 35%; p <0.001) compared with males. Women were less likely to achieve their
      low-density lipoprotein cholesterol (LDLC) (28 vs 32%; p = 0.002), high-density
      lipoprotein cholesterol (HDL-C) (42 vs 50%; p <0.001), and apolipoprotein B (Apo
      B) (38 vs 42%; p = 0.015) targets compared with men. In the very high ASCVD risk
      cohort, women were significantly less likely to achieve their LDL-C (20 vs 30%; p
      <0.001), non- HDL-C (34 vs 39%; p = 0.001) and Apo B (34 vs 41%; p <0.001)
      therapeutic targets compared with men. CONCLUSION: Women in the Arabian Gulf were
      less likely to achieve their lipid targets than men. The difference was more
      significant in the very high ASCVD risk group.

PMID- 27697063
TI  - Primary and Secondary Prevention Trials in Alzheimer Disease: Looking Back,
      Moving Forward.
AB  - The field of Alzheimer disease (AD) prevention has been a culmination of basic
      science, clinical, and translational research. In the past three years since the
      new 2011 AD diagnostic guidelines, large-scale collaborative efforts have
      embarked on new clinical trials with the hope of someday preventing AD. This
      review will shed light on the historical and scientific contexts in which these
      trials were based on, as well as discuss potential challenges these trials may
      face in the coming years. Primary preventive measures, such as lifestyle,
      multidomain, medication, and supplemental interventions, will be analyzed.
      Secondary prevention as represented by disease-modifying interventions, such as
      antiamyloid therapy and pioglitazone, will also be reviewed. Finally, hypotheses
      on future directions for AD prevention trials will be proposed.

PMID- 27697066
TI  - Renal Function Impairment in Patients Undergoing Elective EVAR vs. Elective Open
      Repair During Follow up Period: A Systematic Review of the Literature.
AB  - BACKGROUND: Endovascular (EVAR) or open surgical (OSR) repair are current
      treatment options for abdominal aortic aneurysm (AAA). OBJECTIVE: To produce a
      systematic review comparing the impact of these 2 treatment options on renal
      function during mid- and long term follow up. METHODS: The MEDLINE, EMBASE and
      Cochrane databases and key references were searched. RESULTS: Six studies were
      included from 2000 to 2016, (4 retrospective and 2 RCT studies) reporting on
      2,102 patients (54%; 1096 EVAR, 46%; 1006 OSR). The mean age in EVAR group ranged
      from 69.4 to 73.8 years (91% males), and in OSR group from 68 to 73.6 years (91%
      males). The data were too heterogeneous to perform a meta-analysis. All studies
      used GFR (Glomerular Filtration Rate) or estimated GFR (eGFR) to record renal
      function. The commonest risk factors were the presence of hypertension (77.5%),
      hyperlipidaemia (48.3%), coronary artery disease (42%) and smoking (37.8%).
      During follow up, new events of renal impairment (increase >20% in GFR) in EVAR
      patients and in OSR patients were 58 (5.3%) and 52 (5.2%), respectively. The mean
      GFR was decreased during follow up period in both types of the procedure.
      CONCLUSION: There is lack of definitive evidence to prove the superiority of OSR
      over EVAR regarding renal function in the post-operative follow up period. It
      appears that renal impairment may occur after both interventions. Further
      prospective research is needed to clarify the issue.

PMID- 27697067
TI  - Hypovitaminosis D is Associated with Endothelial Dysfunction in Patients with
      Metabolic Syndrome.
AB  - OBJECTIVES: Recent research has shown that hypovitaminosis D may increase the
      risk of hypertension, vascular disease, diabetes mellitus, obesity and Metabolic
      Syndrome (MetS). Endothelial Dysfunction (ED) is one of the key components of
      MetS which is associated with an imbalance between vasoactive substances such as
      Nitric Oxide (NO) and Endothelins (ET). In this study, we assessed the
      association of 25(OH) D3 level with endothelial dysfunction and subclinical
      atherosclerosis in MetS patients. DESIGN AND METHODS: 105 MetS patients and 48
      controls were included. 25(OH) D3 levels were measured using Ultra-High
      Performance Liquid Chromatography (UHPLC). NOx (NO2 plus NO3) and Endothelin-
      1(ET-1) concentrations were determined along with routine biochemical tests. Flow
      Mediated Dilatation (FMD) and carotid Intima-Media Thickness (cIMT) were measured
      by ultrasonography. RESULTS: In MetS patients, vitamin D and NOx levels were
      significantly lower (p<0.001), while ET-1 levels were higher than controls
      (p<0.005). MetS patients with ED exhibited significantly lower vitamin D levels
      than their counterparts free of ED. Vitamin D levels were correlated positively
      with FMD and NOx, and negatively with systolic blood pressure and body mass
      index. Subclinical atherosclerosis as assessed by the cIMT did not associate with
      low vitamin D levels. CONCLUSION: Vitamin D deficiency seen in MetS patients is
      more prominent in the presence of ED. Hypovitaminosis D may affect endothelial
      cells, and participate in the development of hypertension.

PMID- 27697068
TI  - High-Density Lipoprotein and Low-Density Lipoprotein Subfractions in Patients
      with Chronic Kidney Disease.
AB  - BACKGROUND: Chronic Kidney Disease (CKD) is an independent risk factor for
      cardiovascular disease (CVD). CKD is accompanied by high cardiovascular mortality
      due to many factors, but atherosclerosis is thought to be a major cause at every
      CKD stage. It has been suggested that measuring and estimating changes in high
      density lipoprotein (HDL) and low density lipoprotein (LDL) subfractions may be
      important for predicting CVD in CKD patients. OBJECTIVE: The aim of this study
      was to determine and compare levels of HDL and LDL subfractions in patients with
      different CKD stages. METHODS: The study included 115 patients with CKD (CKD
      stage 2-25 patients, CKD stage 3-25; CKD stage 4-25 and CKD 5 undergoing dialysis
      - 40 patients) and 25 volunteers without CKD (control group). The Lipoprint
      System (Quantimetrix(r)) was used to analyse HDL and LDL subfractions. RESULTS:
      There were significant differences in the distribution of HDL1-HDL5 subfractions
      levels, which were significantly higher in patients with impaired renal function
      than in the control group (p<=.0.013 for all comparisons). HDL7-HDL10
      subfractions were significantly more prevalent in healthy volunteers compared
      with CKD patients (p<=.0.001 for all comparisons). The analysis of LDL
      subfractions revealed significant differences only in IDL-B (p<0.05), IDL-A
      (p<0.05) and LDL2 (p<0.001) between patients with CKD stage 5 and controls.
      CONCLUSION: CKD influenced HDL and LDL subfractions. In CKD patients, large HDL
      subpopulations were more prevalent in contrast to small HDL subfractions in
      healthy subjects. Identification of patients with increased level of large HDL
      subfractions could be useful to identify CKD subjects at increased CV risk.
      Further studies with larger populations and with the application of a several
      methods of subfraction measurement are necessary to confirm these results.

PMID- 27697069
TI  - Kinase Inhibitor Indole Derivatives as Anticancer Agents: A Patent Review.
AB  - Cancer accounts for a number of deaths each year. Consequently, prevention of
      this deadly disease is more challenging and hence the invention of new anticancer
      agents is of utmost importance. The current review elaborates the importance of
      indole designs as patented in the form of anticancer druglike molecules targeting
      different cites of biological arena. Specific attention was given to kinases such
      as platelet-derived growth factor receptor, vascular endothelial growth factor
      receptor and fibroblast growth factor receptor, Bruton's tyrosine kinase,
      anaplastic lymphoma kinase, Janus kinase, cyclin-dependent kinase aurora kinases
      A, B and C, checkpoint kinases, protein kinase R, Pim kinases, phosphoinositide 3
      kinase, altered proteins kinases, polo-like kinase and many more. Moreover, the
      article summarizes the mode of action through the particular functions of kinases
      and the inhibitory potential of indole derivatives toward specific kinase.
      Certain patents gathered in the existing review article suggest that indole core
      can be a versatile foundation to discover drug-like kinase inhibitor molecules
      and modification of substituents existing on the indole moiety may have important
      impact on the pharmacokinetic and pharmacodynamics aspects of the resultant
      scaffolds. The information presented here would gather a great deal of interest
      to identify the new molecular designs bearing indole nucleus presenting novel
      anticancer drugs with a wide variety of biological targets involved in cancer
      pathology focusing on the inhibition of tyrosine kinases, serine/threonine
      specific protein kinases, cyclin-dependent kinases, lipid kinases and altered
      protein kinases.

PMID- 27697070
TI  - Computational Approaches for Translational Oncology: Concepts and Patents.
AB  - BACKGROUND: Cancer is a heterogeneous disease, which is based on an intricate
      network of processes at different spatiotemporal scales, from the genome to the
      tissue level. Hence the necessity for the biomedical and pharmaceutical research
      to work in a multiscale fashion. In this respect, a significant help derives from
      the collaboration with theoretical sciences. Mathematical models can in fact
      provide insights into tumor-related processes and support clinical oncologists in
      the design of treatment regime, dosage, schedule and toxicity. OBJECTIVE AND
      METHOD: The main objective of this article is to review the recent computational
      based patents which tackle some relevant aspects of tumor treatment. We first
      analyze a series of patents concerning the purposing the purposing or repurposing
      of anti-tumor compounds. These approaches rely on pharmacokinetics and
      pharmacodynamics modules, that incorporate data obtained in the different phases
      of clinical trials. Similar methods are also at the basis of other patents
      included in this paper, which deal with treatment optimization, in terms of
      maximizing therapy efficacy while minimizing side effects on the host. A group of
      patents predicting drug response and tumor evolution by the use of kinetics
      graphs are commented as well. We finally focus on patents that implement
      informatics tools to map and screen biological, medical, and pharmaceutical
      knowledge. RESULTS AND CONCLUSIONS: Despite promising aspects (and an increasing
      amount of the relative literature), we found few computational-based patents:
      there is still a significant effort to do for allowing modelling approaches to
      become an integral component of the pharmaceutical research.

PMID- 27697071
TI  - An Evaluation of the Efficacy of Local Hemostatic Measures in Dental Patients
      Taking Oral Anticoagulants: A Critical Review of the Literature Over the Past Two
      Decades.
AB  - The increased risk of bleeding observed in patients on oral anticoagulant therapy
      (OAT) undergoing outpatient oral surgical procedures has been reported in the
      literature and remains a major concern in the care of these patients. This is
      still of great concern to dental surgeons that discontinuing OAT medication
      increases the risk of thromboembolism, while maintaining the therapeutic dose
      increases the risk of hemorrhage. Several local hemostatic measures have been
      used to control bleeding in patients on OAT. However, the effectiveness of these
      measures has not been thoroughly investigated. The aim of this study is to
      evaluate the efficacy of local hemostatic measures in patients taking oral
      anticoagulants. Various databases were searched using the key terms. Selection
      criteria included publications in English, Spanish, or Portuguese within the last
      20 years. The titles and abstracts of papers were initially screened, and reports
      of 18 clinical trials were selected for a critical review and scored according to
      CONSORT 2010 guidelines. The data extracted from these trials represented 1821
      patients receiving OAT, 4116 tooth extractions, and 144 cases of postoperative
      bleeding. In most studies, there were no differences in the effectiveness of
      various local hemostatic measures, and only tranexamic acid was proven effective
      as compared with a placebo group. The reported INR values varied widely among
      studies; the lowest INR value was 0.9 and the highest was 5.0. All local
      hemostatic methods showed low rates of bleeding; and when bleeding occurred, the
      use of these methods was essential for controlling postoperative bleeding. While
      local hemostatic measures appear to be effective in controlling postoperative
      bleeding, additional controlled randomized clinical trials are needed to assess
      the true effectiveness of these measures in patients taking OAT.

PMID- 27697064
TI  - Targeting Tumor Necrosis Factor Alpha for Alzheimer's Disease.
AB  - Alzheimer's disease (AD) affects an estimated 44 million individuals worldwide,
      yet no therapeutic intervention is available to stop the progression of the
      dementia. Neuropathological hallmarks of AD are extracellular deposits of amyloid
      beta (Abeta) peptides assembled in plaques, intraneuronal accumulation of
      hyperphosphorylated tau protein forming tangles, and chronic inflammation. A
      pivotal molecule in inflammation is the pro-inflammatory cytokine TNF-alpha.
      Several lines of evidence using genetic and pharmacological manipulations
      indicate that TNF-alpha signaling exacerbates both Abeta and tau pathologies in
      vivo. Interestingly, preventive and intervention anti-inflammatory strategies
      demonstrated a reduction in brain pathology and an amelioration of cognitive
      function in rodent models of AD. Phase I and IIa clinical trials suggest that TNF
      alpha inhibitors might slow down cognitive decline and improve daily activities
      in AD patients. In the present review, we summarize the evidence pointing towards
      a beneficial role of anti-TNF-alpha therapies to prevent or slow the progression
      of AD. We also present possible physical and pharmacological interventions to
      modulate TNF-alpha signaling in AD subjects along with their limitations.

PMID- 27697072
TI  - Morphometrical and Morphological Alterations of Human Leukocytes Exposed to 1.8
      GHz Electromagnetic Radiations: In Vitro Protective Effects Induced by
      Polyphenols.
AB  - BACKGROUND: Our recent findings have demonstrated that electromagnetic radiations
      (EMR) (1.8 GHz radiofrequency) are able to in vitro induce morphometrical and
      morphological modifications of human leukocytes from normal donors. METHODS: In
      view of the evidence that polyphenols exert many beneficial effects on plants,
      animals and humans, leukocytes from human peripheral blood were pre-treated for 1
      h with two polyphenol preparations from red grape before EMR exposure (1.8 GHz).
      RESULTS: Our data will show that polyphenol pre-treatment reverts to normality
      the morphology of irradiated leukocytes in comparison to irradiated cells only.
      Conversely, leukocyte morphometry seems to be not affected by this treatment.
      CONCLUSION: Here, we demonstrate that polyphenols are also able to normalize
      leukocyte morphology per se altered before as well as after irradiation. Finally,
      a working hypothesis aimed at clarifying the protective mechanisms exerted by
      polyphenols on irradiated leukocytes will be illustrated.

PMID- 27697073
TI  - Cigarette Smoke-mediated Perturbations of the Immune Response: A New Therapeutic
      Approach with Natural Compounds.
AB  - Cigarette smoke (CS) accounts for the outcome of several pathologies, even
      including lung cancer, cardiovascular disease and chronic obstructive pulmonary
      disease (COPD). Under healthy conditions, lung immune system becomes tolerant in
      response to various external stimuli. CS exposure alters the pulmonary immune
      equilibrium, thus leading to a condition of hyper activation of the local innate
      and adaptive immunity. COPD is one of the major complications of chronic CS
      exposure where a pro-inflammatory profile of the pulmonary and systemic immunity
      is predominant. In this review, alternative treatments with natural products to
      mitigate CS-mediated pulmonary inflammation are proposed. In particular,
      polyphenols, a class of natural compounds largely present in fruits and
      vegetables, have been shown to act as anti-inflammatory agents. Accordingly,
      recent experimental and clinical evidences support polyphenol-mediated potential
      health benefits in smokers. For instance, pomegranate juice is able to attenuate
      the damage provoked by CS on cultured human alveolar macrophages. In addition,
      maqui beery extract has been proven to normalize H2O2 and interleukin-6 levels in
      exhaled breath condensate in healthy smokers. However, some limitations of
      alternative treatments are represented by a better knowledge of the mechanism(s)
      of action exerted by polyphenols and by the lack of animal models of COPD. In any
      case, the potential targets of polyphenols in the course of COPD will be outlined
      with special reference to the activation of T regulatory cells as well as to the
      inhibition of the polymorphonuclear cell and monocyte respiratory burst and of
      the NF-kappaB pathway, respectively.

PMID- 27697074
TI  - 18F-FDG-PET Correlates of Impulse Control Disorder in a Diabetic Patient.
AB  - BACKGROUND: Studies have already shown that hyperglycemia and insulin resistance
      are significantly associated with the impairment of cerebral glucose metabolism
      that may secondary lead to cognitive disturbances. In this study, we aimed to
      evaluate the neurometabolic correlates of diabetes in a patient with Intermittent
      explosive disorder (IED). METHODS: We have investigated the cerebral glucose
      metabolism via 2-[18F]-fluoro-2- deoxy-D-glucose positron emission tomography
      (FDG-PET) in a diabetic patient with aggressive outbursts. RESULTS: We have found
      significantly reduced glucose uptake in left temporoparietal region, pontin area,
      and left nucleus lentiformis. DISCUSSION: Our present results indicate decreased
      cerebral glucose metabolism in specific cerebral cortical and subcortical areas.
      The main limitation of this report is that, this is a single case study and that
      these findings need to be replicated in well- conducted randomized controlled
      studies by using additional neuroquantitative methods.

PMID- 27697075
TI  - Sex Impact on Biomarkers, Pharmacokinetics and Pharmacodynamics.
AB  - Sex is one of several factors influencing pharmacological responses, but research
      on its effects on pharmacokinetics and pharmacodynamics, although emerging
      remarkably, remains poor and contains many methodological issues. In this review,
      the current state of knowledge about sex differences in pharmacokinetics and some
      hints to pharmacogenomics were evaluated. Moreover, considering that many
      pharmacological responses are monitored through biomarkers, the influence of sex
      on some biomarkers has been reported. Finally, we report sex differences in
      pharmacodynamics, particularly analysing opioids and their use during pregnancy,
      labor and breastfeeding. In conclusion, a more precise sex- and genderbased
      approach appears necessary to achieve more evidence-based therapy in men and
      women.

PMID- 27697076
TI  - Coffee: A Dietary Intervention on Type 2 Diabetes?
AB  - Coffee beverages, prepared in a multitude of ways around the world, are
      increasingly part of our daily lives. Although considered an unhealthy beverage
      for decades, coffee is increasingly the headline of medical journals in
      association with a reduced risk for several diseases. What if this beverage could
      give us pleasure, while modulating mood and lowering the risk for several
      diseases of the modern society, including type 2 diabetes (T2D)? Based on the
      most recent epidemiological and research data, long-term consumption of coffee
      beverages is associated with a lower risk of developing T2D in healthy
      individuals, probably involving multiple mechanisms, with interventions on
      glucose homeostasis, antioxidant activity, and inflammatory biomarkers. Several
      coffee constituents potentially responsible for these effects are described, as
      well as the factors that make their presence highly variable, with interesting
      effects associated with chlorogenic acids, trigonelline and norharman. Due to the
      high number of compounds contained in coffee, we explore the potential synergic
      effect within the coffee matrix. Moreover, acute coffee consumption shows
      different health effects from those achieved on a long-term daily consumption,
      and not all coffee beverages are similar. Still, despite the huge amount or work
      developed in the last decade, the substances and mechanisms behind these
      protective effects on T2D are still to be fully elucidated, being therefore soon
      for dietary interventions based on coffee.

PMID- 27697077
TI  - Medicinal Plants for Diabetes Treatment During Pregnancy.
AB  - Diabetes mellitus is a syndrome of great importance that affects an increasing
      number of people every day. In particular, diabetes is a common and important
      disease during pregnancy and is marked by complications, both fetal and maternal,
      that increase the risks of morbidity and mortality for diabetic pregnant women
      and their offspring. Drugs such as insulin and hypoglycemic drugs are given to
      treat diabetes, but regular exercise and adequate diet have also been indicated.
      Furthermore, coadjutant therapies such as medicinal plants are popularly used to
      reduce diabetes-induced hyperglycemia, either within or outside the context of
      pregnancy. However, studies examining plant use for diabetes treatment are
      necessary to confirm its possible effects and its safety for the mother and
      fetus. The objective of this literature review was to conduct a survey of plant
      species that are utilized worldwide and their stated therapeutic uses. A
      literature search was performed using the terms "diabetes and pregnancy", which
      resulted in the identification of 31,272 articles. Of these studies, only 12
      (0.0038%) were related to medicinal plants, demonstrating that there has been
      little investigation into this issue. Of the papers analyzed in this review, half
      evaluated plant leaves, indicating that these scientific studies attempted to
      reproduce the preparations commonly used by various populations, i.e., in the
      form of tea. Additionally, more than 90% of studies utilized experimental animals
      to evaluate the maternal-fetal safety of medicinal plant substances that may
      potentially be dangerous for humans. Thus, once confidence levels for plant
      derived substances are established based on toxicological analyses and safety is
      confirmed, it is possible that plants will be used to complement conventional
      diabetes therapies.

PMID- 27697079
TI  - Resting-state brain alteration after a single dose of SSRI administration
      predicts 8-week remission of patients with major depressive disorder.
AB  - BACKGROUND: The present study investigated alteration of brain resting-state
      activity induced by antidepressant treatment and attempted to investigate whether
      treatment efficacy can be predicted at an early stage of pharmacological
      treatment. METHOD: Forty-eight first-episode medication-free patients diagnosed
      with major depression received treatment with escitalopram. Resting-state
      functional magnetic resonance imaging was administered prior to treatment, 5 h
      after the first dose, during the course of pharmacological treatment (week 4) and
      at endpoint (week 8). Resting-state activity was evaluated in the course of the 8
      week treatment and in relation to clinical improvement. RESULTS: Escitalopram
      dynamically modified resting-state activity in depression during the treatment.
      After 5 h the antidepressant induced a significant decrease in the signal in the
      occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal
      cortices and middle cingulate cortex. Furthermore, while remitters demonstrated
      more obvious changes following treatment, these were more modest in non
      responders suggesting possible tonic and dynamic differences in the serotonergic
      system. Changes after 5 h in the caudate, occipital and temporal cortices were
      the best predictor of clinical remission at endpoint. CONCLUSIONS: This study
      revealed the possibility of using the measurement of resting-state neural changes
      a few hours after acute administration of antidepressant to identify individuals
      likely to remit after a few weeks of treatment.

PMID- 27697078
TI  - Longitudinal alterations in motivational salience processing in ultra-high-risk
      subjects for psychosis.
AB  - BACKGROUND: Impairments in the attribution of salience are thought to be
      fundamental to the development of psychotic symptoms and the onset of psychotic
      disorders. The aim of the present study was to explore longitudinal alterations
      in salience processing in ultra-high-risk subjects for psychosis. METHOD: A total
      of 23 ultra-high-risk subjects and 13 healthy controls underwent functional
      magnetic resonance imaging at two time points (mean interval of 17 months) while
      performing the Salience Attribution Test to assess neural responses to task
      relevant (adaptive salience) and task-irrelevant (aberrant salience) stimulus
      features. RESULTS: At presentation, high-risk subjects were less likely than
      controls to attribute salience to relevant features, and more likely to attribute
      salience to irrelevant stimulus features. These behavioural differences were no
      longer evident at follow-up. When attributing salience to relevant cue features,
      ultra-high-risk subjects showed less activation than controls in the ventral
      striatum at both baseline and follow-up. Within the high-risk sample,
      amelioration of abnormal beliefs over the follow-up period was correlated with an
      increase in right ventral striatum activation during the attribution of salience
      to relevant cue features. CONCLUSIONS: These findings confirm that salience
      processing is perturbed in ultra-high-risk subjects for psychosis, that this is
      linked to alterations in ventral striatum function, and that clinical outcomes
      are related to longitudinal changes in ventral striatum function during salience
      processing.

PMID- 27697080
TI  - Evidence of leptospirosis in the kidneys and serum of feral swine (Sus scrofa) in
      the United States.
AB  - Leptospirosis is the most widespread zoonosis in humans worldwide. In the United
      States, widespread detection of antibodies to leptospirosis have been identified
      in feral swine (Sus scrofa) with the highest detection of serovars, Bratislava,
      Icterohaemorrhagiae, and Pomona. Over the past few years, feral swine populations
      have expanded their geographical range and distribution in the United States with
      reports in at least 39 of 50 states. Since feral swine serve as reservoirs for
      serovars that can infect humans, it is important to understand the risk of
      transmission. In order to learn more about the probability that feral swine shed
      infectious leptospires, we collected kidneys and paired serum when possible from
      677 feral swine in 124 counties of 29 states. These counties had previously been
      identified as antibody positive for Leptospira interrogans serovars Bratislava,
      Canicola, Grippotyphosa, Hardjo, Icterohaemorrhagiae or Pomona. Although exposure
      to these same six serovars of leptospirosis continued to be high (53% overall) in
      the counties we sampled, we detected leptospiral DNA in only 3.4% of feral swine
      kidneys tested. Based on these results, it appears that although feral swine can
      serve as a source of infection to humans, especially in those who are more likely
      to encounter them directly such as wildlife biologists, veterinarians, and
      hunters, the risk may be relatively low. However, further studies to examine the
      relationship between leptospiral shedding in the urine and kidneys in addition to
      culturing the organism are recommended in order to better understand the risk
      associated with feral swine.

PMID- 27697081
TI  - Seroprevalence of Middle East Respiratory Syndrome Coronavirus Among Healthcare
      Personnel Caring for Patients With Middle East Respiratory Syndrome in South
      Korea.

PMID- 27697082
TI  - Prevalence, risk factors, and the desire for help of distressed newly diagnosed
      cancer patients: A large-sample study.
AB  - OBJECTIVE: Beginning in 2007, all newly diagnosed cancer patients at the Koo
      Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were screened for psychosocial
      distress. Our social workers, as part of the psychosocial care team (PCT), have
      engaged in proactive outreach with patients identified as distressed. The goal of
      the present study was to assess the prevalence of psychosocial distress and the
      extent of contact between the PCT and distressed patients. METHOD: Newly
      diagnosed patients who were treated at KF-SYSCC between 2007 and 2010 for cancer
      were eligible if there were at least 100 patients with the same type of cancer.
      Before treatment began, they were screened with the Pain Scale and the Distress
      Thermometer (DT) and had the option to specify a desire for help. The rates of
      distress were analyzed by cancer type and by probable related factors.
      Information regarding contact with the PCT was retrieved from computerized
      databases. RESULTS: Overall, some 5,335 cancer patients representing 12 major
      cancer types were included in our study. Of these, 1,771 (33.20%) were
      significantly distressed. By multivariate logistic regression, younger age,
      female gender, higher pain score, and disease stage, but not cancer type, were
      found to be associated with higher rates of distress. Among these distressed
      patients, 628 (36%) had some contact with the PCT. SIGNIFICANCE OF RESULTS: This
      Taiwanese study with a large sample size revealed a prevalence rate of
      psychosocial distress similar to rates found in Western countries. Contact with
      the PCT was established in only 36% of significantly distressed patients, despite
      a proactive outreach program. It is very important to have screening results made
      available in a timely fashion to the psycho-oncology team so that appropriate
      care can be offered promptly.

PMID- 27697084
TI  - Environmental Exposures and the Risk of Central Venous Catheter Complications and
      Readmissions in Home Infusion Therapy Patients.
AB  - BACKGROUND Patients are frequently discharged with central venous catheters
      (CVCs) for home infusion therapy. OBJECTIVE To study a prospective cohort of
      patients receiving home infusion therapy to identify environmental and other risk
      factors for complications. DESIGN Prospective cohort study between March and
      December 2015. SETTING Home infusion therapy after discharge from academic
      medical centers. PARTICIPANTS Of 368 eligible patients discharged from 2 academic
      hospitals to home with peripherally inserted central catheters and tunneled CVCs,
      222 consented. Patients remained in the study until 30 days after CVC removal.
      METHODS Patients underwent chart abstraction and monthly telephone surveys while
      the CVC was in place, focusing on complications and environmental exposures.
      Multivariable analyses estimated adjusted odds ratios and adjusted incident rate
      ratios between clinical, demographic, and environmental risk factors and 30-day
      readmissions or CVC complications. RESULTS Of 222 patients, total parenteral
      nutrition was associated with increased 30-day readmissions (adjusted odds ratio,
      4.80 [95% CI, 1.51-15.21) and CVC complications (adjusted odds ratio, 2.41 [95%
      CI, 1.09-5.33]). Exposure to soil through gardening or yard work was associated
      with a decreased likelihood of readmissions (adjusted odds ratio, 0.09 [95% CI,
      0.01-0.74]). Other environmental exposures were not associated with CVC
      complications. CONCLUSIONS complications and readmissions were common and
      associated with the use of total parenteral nutrition. Common environmental
      exposures (well water, cooking with raw meat, or pets) did not increase the rate
      of CVC complications, whereas soil exposures were associated with decreased
      readmissions. Interventions to decrease home CVC complications should focus on
      total parenteral nutrition patients. Infect Control Hosp Epidemiol 2016;1-8.

PMID- 27697085
TI  - Poor stimulus discriminability as a common neuropsychological deficit between
      ADHD and reading ability in young children: a moderated mediation model.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is frequently
      associated with poorer reading ability; however, the specific neuropsychological
      domains linking this co-occurrence remain unclear. This study evaluates
      information-processing characteristics as possible neuropsychological links
      between ADHD symptoms and RA in a community-based sample of children and early
      adolescents with normal IQ (?70). METHOD: The participants (n = 1857, aged 6-15
      years, 47% female) were evaluated for reading ability (reading single words
      aloud) and information processing [stimulus discriminability in the two-choice
      reaction-time task estimated using diffusion models]. ADHD symptoms were
      ascertained through informant (parent) report using the Development and Well
      Being Assessment (DAWBA). Verbal working memory (VWM; digit span backwards),
      visuospatial working memory (VSWM, Corsi Blocks backwards), sex, socioeconomic
      status, and IQ were included as covariates. RESULTS: In a moderated mediation
      model, stimulus discriminability mediated the effect of ADHD on reading ability.
      This indirect effect was moderated by age such that a larger effect was seen
      among younger children. CONCLUSION: The findings support the hypothesis that ADHD
      and reading ability are linked among young children via a neuropsychological
      deficit related to stimulus discriminability. Early interventions targeting
      stimulus discriminability might improve symptoms of inattention/hyperactivity and
      reading ability.

PMID- 27697087
TI  - Sustained High Level of Healthcare Worker Adherence With Hand Hygiene Practice
      Recommendations Using the Patient-as-Observer Approach in the Ambulatory Setting.
AB  - We report on a quality improvement initiative for hand hygiene adherence using
      the patient-as-observer method in the ambulatory setting. There were 604,661
      observations recorded with improvement of adherence from 88% to 95% or greater;
      alcohol-based hand sanitizer purchasing correlated with this increase. This
      sustainable method effectively ensures hand hygiene adherence. Infect Control
      Hosp Epidemiol 2016;1496-1498.

PMID- 27697083
TI  - Post-traumatic stress disorder and cardiometabolic disease: improving causal
      inference to inform practice.
AB  - Post-traumatic stress disorder (PTSD) has been declared 'a life sentence' based
      on evidence that the disorder leads to a host of physical health problems. Some
      of the strongest empirical research - in terms of methodology and findings - has
      shown that PTSD predicts higher risk of cardiometabolic diseases, specifically
      cardiovascular disease (CVD) and type 2 diabetes (T2D). Despite mounting
      evidence, PTSD is not currently acknowledged as a risk factor by cardiovascular
      or endocrinological medicine. This view is unlikely to change absent compelling
      evidence that PTSD causally contributes to cardiometabolic disease. This review
      suggests that with developments in methods for epidemiological research and the
      rapidly expanding knowledge of the behavioral and biological effects of PTSD the
      field is poised to provide more definitive answers to questions of causality.
      First, we discuss methods to improve causal inference using the observational
      data most often used in studies of PTSD and health, with particular reference to
      issues of temporality and confounding. Second, we consider recent work linking
      PTSD with specific behaviors and biological processes, and evaluate whether these
      may plausibly serve as mechanisms by which PTSD leads to cardiometabolic disease.
      Third, we evaluate how looking more comprehensively into the PTSD phenotype
      provides insight into whether specific aspects of PTSD phenomenology are
      particularly relevant to cardiometabolic disease. Finally, we discuss new areas
      of research that are feasible and could enhance understanding of the PTSD
      cardiometabolic relationship, such as testing whether treatment of PTSD can halt
      or even reverse the cardiometabolic risk factors causally related to CVD and T2D.

PMID- 27697086
TI  - Infection Prevention and Antimicrobial Stewardship Knowledge for Selected
      Infections Among Nursing Home Personnel.
AB  - OBJECTIVE To assess knowledge about infection prevention among nursing home
      personnel and identify gaps potentially addressable through a quality improvement
      collaborative. DESIGN Baseline knowledge assessment of catheter-associated
      urinary tract infection, asymptomatic bacteriuria, antimicrobial stewardship, and
      general infection prevention practices for healthcare-associated infections.
      SETTING Nursing homes across 14 states participating in the national "Agency for
      Healthcare Research and Quality Safety Program for Long-Term Care: Healthcare
      Associated Infections/Catheter-Associated Urinary Tract Infection." PARTICIPANTS
      Licensed (RNs, LPNs, APRNs, MDs) and unlicensed (clinical nursing assistants)
      healthcare personnel. METHODS Each facility aimed to obtain responses from at
      least 10 employees (5 licensed and 5 unlicensed). We assessed the percentage of
      correct responses. RESULTS A total of 184 (78%) of 236 participating facilities
      provided 1 response or more. Of the 1,626 respondents, 822 (50.6%) were licensed;
      117 facilities (63.6%) were for-profit. While 99.1% of licensed personnel
      recognized the definition of asymptomatic bacteriuria, only 36.1% knew that
      pyuria could not distinguish a urinary tract infection from asymptomatic
      bacteriuria. Among unlicensed personnel, 99.6% knew to notify a nurse if a
      resident developed fever or confusion, but only 27.7% knew that cloudy, smelly
      urine should not routinely be cultured. Although 100% of respondents reported
      receiving training in hand hygiene, less than 30% knew how long to rub hands
      (28.5% licensed, 25.2% unlicensed) or the most effective agent to use (11.7%
      licensed, 10.6% unlicensed). CONCLUSIONS This national assessment demonstrates an
      important need to enhance infection prevention knowledge among healthcare
      personnel working in nursing homes to improve resident safety and quality of
      care. Infect. Control Hosp. Epidemiol. 2016;1-6.

PMID- 27697090
TI  - Overexpression of SCUBE2 Inhibits Proliferation, Migration, and Invasion in
      Glioma Cells.
AB  - Signal peptide CUB EGF-like domain-containing protein 2 (SCUBE2), a member of the
      SCUBE family of proteins, was recently found to play an important role in cancer
      development. However, little is known regarding its biological function in
      glioma. In the present study, we investigated the effect of SCUBE2 on glioma and
      explored its relevant mechanisms. The study showed that SCUBE2 had a low
      expression in glioma tissue and cell lines. SCUBE2 overexpression inhibited
      glioma cell proliferation in vitro and in vivo as well as suppressed glioma cell
      migration and invasion in vitro. Furthermore, we found that the Sonic hedgehog
      (Shh) signaling pathway was involved in the inhibitory effect of SCUBE2
      overexpression on glioma cells. In light of the results obtained from our study,
      SCUBE2 may be regarded as a potential therapeutic target for glioma.

PMID- 27697089
TI  - Human cysticercosis in Portugal: long gone or still contemporary?
AB  - Cysticercosis, a leading cause of acquired epilepsy in developing countries, has
      been controlled or eradicated in industrialized countries. This paradigm has
      recently been challenged, with human neurocysticercosis (NCC) being increasingly
      diagnosed in these countries. In order to assess the NCC burden in Portugal, a
      retrospective study on NCC hospitalizations (2006-2013) was conducted based on
      the national database on hospital morbidity: 357 hospitalized cases were
      detected. NCC was most frequent in the following age groups: 20-64 years (n =
      197, 55.2%) >64 years (n = 111, 31.1%), and <20 years (n = 49, 13.7%). In the
      Norte and Centro regions cases tended to be older than in the Lisboa and Vale do
      Tejo Region. The results raise concerns for imported and autochthonous disease,
      suggesting the Lisboa and Vale do Tejo Region, due to its higher frequency of
      cases at younger ages, as a priority for research and intervention, and further
      suggest that NCC should be under surveillance (notifiable). The National
      Observatory of Cysticercosis and Taeniasis has been established and will define
      NCC cases as well as monitoring and surveillance.

PMID- 27697088
TI  - Neuropsychological Profile of Lifetime Traumatic Brain Injury in Older Veterans.
AB  - OBJECTIVES: The aim of this study was to characterize the neuropsychological
      profile of lifetime traumatic brain injury (TBI) in older Veterans. METHODS:
      Participants were 169 older Veterans [mean age=79.1 years (range, 51-97 years),
      89% male, 92% Caucasian], 88 with lifetime TBI and 81 without TBI, living in
      Veterans' retirement homes in independent residence. TBI history was ascertained
      with the Ohio State TBI Identification Method structured interview. Cognition was
      assessed with neuropsychological tests: Raw scores were converted to Z-scores
      compared to age-corrected normative data and combined into five domain composite
      Z-scores (attention/working memory, learning/memory, language, processing speed,
      executive functioning). We investigated the association between TBI and
      performance in each cognitive domain in linear mixed effects models, with and
      without adjustment for demographics, medical comorbidities, and psychiatric
      variables. RESULTS: Compared to those without TBI, older Veterans with TBI had
      greater deficits in processing speed (estimate=-.52; p=.01; f 2=.08 in fully
      adjusted model) and executive functioning (estimate=-.41; p=.02; f 2=.06 in fully
      adjusted model) but performed similarly in the attention/working memory,
      learning/memory, and language domains (all p>.05). TBI-associated deficits were
      most prominent among individuals with multiple mild TBIs and those with any
      moderate-to-severe TBI, but were not clearly present among those with single mild
      TBI. CONCLUSIONS: The neuropsychological profile of lifetime TBI in older
      Veterans is characterized by slowed processing speed and executive dysfunction,
      especially among those with greater injury burden. This pattern may reflect long
      standing deficits or a TBI-associated cognitive decline process distinct from
      Alzheimer's disease. (JINS, 2017, 23, 56-64).

PMID- 27697091
TI  - Demethylation of Repressor Element-1 Silencing Transcription (REST) Suppresses
      the Malignant Phenotype of Breast Cancer via MMP9.
AB  - Breast cancer is the leading cause of cancer deaths in females all over the
      world, mainly resulting from metastasis. Previous studies have revealed that
      repressor element-1 (RE-1) silencing transcription (REST) acted as a tumor
      suppressor in breast cancer. However, the mechanism by which REST is regulated
      remains unknown, and its role in the metastasis in breast cancer cells remains
      unclear. In the present study, we showed that the expression of REST was lower in
      breast cancer samples than that of adjacent samples by immunohistochemical
      analysis, which may be due to hypermethylation of the REST promoter. Low REST
      levels are significantly associated with malignant progression in breast cancer
      patients. Additionally, we elucidated the functions of REST on proliferation and
      invasion in breast cancer cells. Lentivirus transfection was used to overexpress
      REST in human breast MDA-MB-231 cells. Then the biologic consequences of
      overexpressing REST in regard to cell proliferation, apoptosis, and invasion were
      determined. Furthermore, we also determined matrix metalloproteinase-9 (MMP9) as
      a target of REST. These results demonstrate that downregulation of REST, a tumor
      suppressor in breast cancer, is associated with hypermethylation. Induced REST
      expression is capable of attenuating invasion ability of breast cancer cells,
      which may be a novel strategy for metastatic breast cancer treatment.

PMID- 27697092
TI  - miR-935 Promotes Liver Cancer Cell Proliferation and Migration by Targeting SOX7.
AB  - Hepatocellular carcinoma (HCC) is the most common cancer in the world. MicroRNAs
      (miRNAs) are a type of small noncoding RNA that can regulate the expression of
      target genes under physiological and pathophysiological conditions. Aberrant
      expression of microRNA-935 (miR-935) has been reported in cancer studies.
      However, its expression and mechanism in HCC remain unclear. In our study, we
      found that miR-935 was upregulated in liver cancer tissues and cells.
      Overexpression of miR-935 in liver cells promoted cell proliferation,
      tumorigenesis, and cell cycle progression, whereas inhibition of miR-935 reduced
      cell proliferation, tumorigenicity, and cell cycle progression. These changes in
      the properties of HCC cells were associated with upregulation of two well-known
      cellular G1/S transitional regulators: cyclin D1 and c-Myc. Additionally, we
      identified SOX7 as a direct target of miR-935. Overexpression of miR-935
      inhibited SOX7 expression but promoted the levels of c-Myc and cyclin D1, which
      promotes cell proliferation and tumorigenesis; knockdown of miR-935 increased
      SOX7 level and inhibited c-Myc and cyclin D1 expression, whereas SOX7 silencing
      could promote cell proliferation, cell motility, and invasiveness in vitro. Our
      findings suggest that miR-935 represents a biomarker and a potential new target
      in HCC progression by suppressing SOX7 expression.

PMID- 27697093
TI  - Knockdown of DDX46 Inhibits the Invasion and Tumorigenesis in Osteosarcoma Cells.
AB  - DDX46, a member of the DEAD-box (DDX) helicase family, is involved in the
      development of several tumors. However, the exact role of DDX46 in osteosarcoma
      and the underlying mechanisms in tumorigenesis remain poorly understood. Thus, in
      the present study, we explored the role of DDX46 in osteosarcoma and the
      underlying mechanisms. Our results demonstrated that the expression levels of
      DDX46 in both mRNA and protein were greatly elevated in human osteosarcoma
      tissues and cell lines. Knockdown of DDX46 obviously inhibited osteosarcoma cell
      proliferation and tumor growth in vivo. In addition, knockdown of DDX46 also
      significantly suppressed migration and invasion in osteosarcoma cells.
      Furthermore, knockdown of DDX46 substantially downregulated the phosphorylation
      levels of PI3K and Akt in SaOS2 cells. In summary, the present results have
      revealed that DDX46 plays an important role in osteosarcoma growth and
      metastasis. Knockdown of DDX46 inhibited osteosarcoma cell proliferation,
      migration, and invasion in vitro and tumor growth in vivo. Therefore, DDX46 may
      be a potential therapeutic target for the treatment of osteosarcoma.

PMID- 27697094
TI  - Determination of Withanolides in Withania somnifera by Liquid Chromatography:
      Single-Laboratory Validation, First Action 2015.17.
AB  - An LC method was developed and validated in 2007 for analyzing Withania somnifera
      raw material (root) and dried extracts for withanolide content, including
      withanoside IV, withanoside V, withaferin A, 12-deoxywithastromonolide,
      withanolide A, and withanolide B. The method involved the extraction of the
      analytes with methanol, their subsequent filtration, and then analysis on a C18
      column with an acetonitrile gradient and UV detection. Single-laboratory
      validation yielded linearity generally in the range of 20 to 200 MUg/mL for each
      analyte, with a repeatability precision of RSD < 3% in most cases, and recovery
      in the range of 90 to 105%. These results compare well with the performance
      criteria recently detailed in AOAC Standard Method Performance Requirement
      2015.007. The method was shown to be rugged with respect to different analysts,
      equipment, and days of analysis, and the sample solution was shown to be stable
      for 24 h at room temperature after extraction. The method was reviewed by the
      AOAC Expert Review Panel on Dietary Supplements (Set 2 Ingredients) and approved
      for First Action Official MethodSM status.

PMID- 27697095
TI  - MicroRNA-509-3p Inhibits Cancer Cell Proliferation and Migration via Upregulation
      of XIAP in Gastric Cancer Cells.
AB  - Gastric cancer (GC) is the fourth most common cancer globally. Recently,
      microRNAs (miRNAs) have been suggested to be closely associated with
      tumorigenesis. Aberrant expression of miR-509-3p has been reported in cancer
      studies. However, the expression and mechanism of its function in GC remain
      unclear. Here we showed that miR-509-3p was downregulated in GC specimens, which
      was associated with overall survival. Functional investigations demonstrated that
      the overexpression of miR-509-3p inhibited the migration and proliferation of the
      GC cells. Additionally, we identified X-linked inhibitor of apoptosis protein
      (XIAP) as a direct target of miR-509-3p. Knockdown of XIAP significantly
      attenuated the ability of proliferation, migration, and invasion of GC cells. The
      data therefore suggest that miR-509-3p plays an important role in the development
      and progression of GC, implicating possible applications in the clinic as a
      biomarker and a potential new target.

PMID- 27697096
TI  - Changes in Sexual Behavior of Orchidectomized Rats Under Influence of
      Allotransplantation of Testicular Interstitial Cell Suspension.
AB  - Transplantation of hormone-producing cells is an experimental endocrine
      dysfunction treatment. The present study investigated the effects of orchidectomy
      (OE) and transplantation of interstitial cell suspension (ICS) on rat sexual
      behavior. Adult experimental animals were divided into two populations. One of
      these populations had sexual experience before the experiment and the other did
      not. Each population was divided into three groups: control group and two
      orchidectomized groups. One of the orchidectomized groups was treated with ICS,
      and the other was treated with the vehicle. The changes in the sexual behavior
      were investigated on the following parameters: mount latency (ML), intromission
      latency (IL), ejaculation latency (EL), mount frequency (MF), intromission
      frequency (IF), copulatory efficacy (CE), and IF/EL ratio. The investigation of
      these changes lasted 4 weeks after ICS transplantation. The parameters of sexual
      behavior reflected a decrease in sexual function after OE at the beginning of the
      observation, especially for the animals that did not have a sexual experience.
      However, it was shown that sexual activity increased in the following 4 weeks. We
      have indicated that the loss of gonads attenuated the capacity to acquire sexual
      experience; nonetheless, it did not mean that the animals completely lost this
      capacity. Transplantation of ICS facilitated the maintenance of male sexual
      behavior after OE, fractionally enlarged the size of regressed seminal vesicles
      of the animals, and increased the free testosterone (T) level. These findings
      suggest the ICS can be considered as a temporal source of androgens, which can
      facilitate a restoration of sexual activity.

PMID- 27697097
TI  - Chromatographic Analysis of a Multicomponent Mixture of B1, B6, B12,
      Benfotiamine, and Diclofenac; Part I: HPLC and UPLC Methods for the Simultaneous
      Quantification of These Five Components in Tablets and Capsules.
AB  - New, simple, highly sensitive, precise, and accurate gradient reversed-phase
      chromatographic methods were developed using HPLC and ultra-HPLC (UPLC) systems
      for the determination of five components, namely thiamine, pyridoxine,
      cyanocobalamin, benfotiamine, and diclofenac in tablets and capsules. The methods
      were compared for their efficiency in the separation and determination of these
      five compounds using two different C18 columns (250 * 4.6 mm, 5 MUm; and 100 *
      4.6 mm, 2.6 MUm) for HPLC and UPLC, respectively. Chromatographic separation was
      performed with a mobile phase containing acetonitrile and 0.025 M phosphate
      buffer (pH 3.5), with a gradient program and a flow rate of 1.5 and 1.0 mL/min
      for both methods, respectively. The methods were validated according to
      International Conference on Harmonization guidelines. Linearity was achieved in
      the range of 5.00 to 150.00 MUg/mL for each of the five compounds. Ruggedness and
      intermediate precision were confirmed by different analysts on different columns
      on different days. Moreover, the components were subjected to an accelerated
      stability study under acidic, alkaline, and oxidative stress conditions and no
      interfering peaks were observed. The five compounds were efficiently separated in
      <20 min by HPLC, whereas for UPLC, separation was achieved in <8 min, which
      dramatically decreased the consumption of organic solvents.

PMID- 27697098
TI  - High-Level Expression of RIPK4 and EZH2 Contributes to Lymph Node Metastasis and
      Predicts Favorable Prognosis in Patients With Cervical Cancer.
AB  - The investigation of specific genes will establish more useful biomarkers for
      accurate detection and management of gynecological cancers, especially patients
      with cervical cancer (CCP). The aim of this study was to evaluate the expression
      level of RIPK4 and EZH2 messenger RNA (RIPK4 and EZH2 mRNA) in CCP. Expression of
      RIPK4 and EZH2 in the tissues was determined by immunohistochemistry and qRT-PCR
      methods. Correlations of RIPK4 and EZH2 mRNA with clinical and pathological
      parameters were analyzed using the Fisher's exact test. The mRNA level of RIPK4
      was significantly upregulated in tumor tissues compared with matched adjacent
      normal tissues (4.10 +/- 0.89 vs. 1.5 +/- 0.82; p = 0.021). EZH2 mRNA was
      increased in cancer tissues compared to normal tissues (3.54 +/- 0.71 vs. 1.2 +/-
      0.65; p = 0.003). High expression of RIPK4 was observed in 25 patients (64.1%),
      whereas weak expression was seen in 14 cases (35.9%). Furthermore, the expression
      of RIPK4 was overexpressed in matched adjacent normal tissues (p = 0.004). FIGO
      stage and lymph node metastasis were significantly linked to a higher expression
      of RIPK4 (p < 0.05). Overexpression of EZH2 was found in 30 patients (76.9%) and
      was associated with FIGO stage, histological type, and lymph node metastasis (p <
      0.05). In conclusion, our data suggest that RIPK4/EZH2 markers might be used as
      potential predictors of prognosis in cervical cancer.

PMID- 27697099
TI  - High TRAF6 Expression Is Associated With Esophageal Carcinoma Recurrence and
      Prompts Cancer Cell Invasion.
AB  - Esophageal cancer is one of the most common types of cancer, and it has a poor
      prognosis. The molecular mechanisms of esophageal cancer progression remain
      largely unknown. In this study, we aimed to investigate the clinical significance
      and biological function of tumor necrosis factor receptor-associated factor 6
      (TRAF6) in esophageal cancer. Expression of TRAF6 in esophageal cancer was
      examined, and its correlation with clinicopathological factors and patient
      prognosis was analyzed. A series of functional and mechanism assays were
      performed to further investigate the function and underlying mechanisms in
      esophageal cancer. Expression of TRAF6 was highly elevated in esophageal cancer
      tissues, and patients with high TRAF6 expression have a significantly shorter
      survival time than those with low TRAF6 expression. Furthermore, loss-of-function
      experiments showed that knockdown of TRAF6 significantly reduced the migration
      and invasion abilities of esophageal cancer cells. Moreover, the pro-oncogenic
      effects of TRAF6 in esophageal cancer were mediated by the upregulation of AEP
      and MMP2. Altogether, our data suggest that high expression of TRAF6 is
      significant for esophageal cancer progression, and TRAF6 indicates poor prognosis
      in esophageal cancer patients, which might be a novel prognostic biomarker or
      potential therapeutic target in esophageal cancer.

PMID- 27697100
TI  - WITHDRAWN: CXCR4 promotes growth and sphere formation of hypoxic breast cancer
      side 7 population cells via activation of c-Jun/ABCG2 pathway.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 27697101
TI  - Use of Carbon Nanotubes for the Analysis of Pesticide Residues in Fruits and
      Vegetables.
AB  - This review presents the application of carbon nanotubes as sorbent materials in
      the analysis of pesticide residues in fruits and vegetables. The advantages,
      limitations, and challenges of carbon nanotubes, with respect to their use in
      analytical chemistry, are presented. The efficiency of their application as
      extraction sorbent materials (in terms of LOD, LOQ, linearity, relative recovery,
      and RSD) in SPE, solid-phase microextraction, multi-plug filtration clean-up,
      matrix solid-phase dispersion, and the quick, easy, cheap, effective, rugged and
      safe method is reported. The synthesis, functionalization, purification, and
      characterization methods of carbon nanotubes are also discussed.

PMID- 27697102
TI  - Use of Carbon Nanotubes for the Analysis of Pesticide Residues in Fruits and
      Vegetables.
AB  - This review presents the application of carbon nanotubes as sorbent materials in
      the analysis of pesticide residues in fruits and vegetables. The advantages,
      limitations, and challenges of carbon nanotubes, with respect to their use in
      analytical chemistry, are presented. The efficiency of their application as
      extraction sorbent materials (in terms of LOD, LOQ, linearity, relative recovery,
      and RSD) in SPE, solid-phase microextraction, multi-plug filtration clean-up,
      matrix solid-phase dispersion, and the quick, easy, cheap, effective, rugged and
      safe method is reported. The synthesis, functionalization, purification, and
      characterization methods of carbon nanotubes are also discussed.

PMID- 27697103
TI  - Cell Therapy Regulation in Taiwan.
AB  - Cell therapy is not only a novel medical practice but also a medicinal product
      [cell therapy product (CTP)]. More and more CTPs are being approved for marketing
      globally because of the rapid development of biomedicine in cell culture,
      preservation, and preparation. However, regulation is the most important
      criterion for the development of CTPs. Regulations must be flexible to expedite
      the process of marketing for new CTPs. Recently, the Taiwan Food and Drug
      Administration (TFDA) updated the related regulations such as regulation of
      development, current regulatory framework and process, and the application and
      evaluation processes. When the quality of CTPs has been improved significantly,
      their safety and efficacy are further ensured. The treatment protocol, a new
      design for adaptive licensing to current clinical practice, is a rapid process
      for patients with life-threatening diseases or serious conditions for which there
      are no suitable drugs, medical devices, or other therapeutic methods available.
      The hospital can submit the treatment protocol to apply for cell therapy as a
      medical practice, which may result in easier and faster cell therapy development,
      and personalized treatment for individual patients will evolve quickly.

PMID- 27697104
TI  - Validation of the Applied Biosystems RapidFinder Shiga Toxin-Producing E. coli
      (STEC) Detection Workflow.
AB  - The Applied BiosystemsTM RapidFinderTM STEC Detection Workflow (Thermo Fisher
      Scientific) is a complete protocol for the rapid qualitative detection of
      Escherichia coli (E. coli) O157:H7 and the "Big 6" non-O157 Shiga-like toxin
      producing E. coli (STEC) serotypes (defined as serogroups: O26, O45, O103, O111,
      O121, and O145). The RapidFinder STEC Detection Workflow makes use of either the
      automated preparation of PCR-ready DNA using the Applied Biosystems PrepSEQTM
      Nucleic Acid Extraction Kit in conjunction with the Applied Biosystems MagMAXTM
      Express 96-well magnetic particle processor or the Applied Biosystems PrepSEQ
      Rapid Spin kit for manual preparation of PCR-ready DNA. Two separate assays
      comprise the RapidFinder STEC Detection Workflow, the Applied Biosystems
      RapidFinder STEC Screening Assay and the Applied Biosystems RapidFinder STEC
      Confirmation Assay. The RapidFinder STEC Screening Assay includes primers and
      probes to detect the presence of stx1 (Shiga toxin 1), stx2 (Shiga toxin 2), eae
      (intimin), and E. coli O157 gene targets. The RapidFinder STEC Confirmation Assay
      includes primers and probes for the "Big 6" non-O157 STEC and E. coli O157:H7.
      The use of these two assays in tandem allows a user to detect accurately the
      presence of the "Big 6" STECs and E. coli O157:H7. The performance of the
      RapidFinder STEC Detection Workflow was evaluated in a method comparison study,
      in inclusivity and exclusivity studies, and in a robustness evaluation. The
      assays were compared to the U.S. Department of Agriculture (USDA), Food Safety
      and Inspection Service (FSIS) Microbiology Laboratory Guidebook (MLG) 5.09:
      Detection, Isolation and Identification of Escherichia coli O157:H7 from Meat
      Products and Carcass and Environmental Sponges for raw ground beef (73% lean) and
      USDA/FSIS-MLG 5B.05: Detection, Isolation and Identification of Escherichia coli
      non-O157:H7 from Meat Products and Carcass and Environmental Sponges for raw beef
      trim. No statistically significant differences were observed between the
      reference method and the individual or combined kits forming the candidate assay
      using either of the DNA preparation kits (manual or automated extraction). For
      the inclusivity and exclusivity evaluation, the RapidFinder STEC Detection
      Workflow, comprising both RapidFinder STEC screening and confirmation kits,
      correctly identified all 50 target organism isolates and correctly excluded all
      30 nontarget strains for both of the assays evaluated. The results of these
      studies demonstrate the sensitivity and selectivity of the RapidFinder STEC
      Detection Workflow for the detection of E. coli O157:H7 and the "Big 6" STEC
      serotypes in both raw ground beef and beef trim. The robustness testing
      demonstrated that minor variations in the method parameters did not impact the
      accuracy of the assay and highlighted the importance of following the correct
      incubation temperatures.

PMID- 27697105
TI  - Caffeine-induced food-avoidance behavior is mediated by neuroendocrine signals in
      Caenorhabditis elegans.
AB  - High-dose caffeine uptake is a developmental stressor and causes food-avoidance
      behavior (aversion phenotype) in C. elegans, but its mode of action is largely
      unknown. In this study, we investigated the molecular basis of the
      caffeineinduced aversion behavior in C. elegans. We found that aversion phenotype
      induced by 30 mM caffeine was mediated by JNK/MAPK pathway, serotonergic and
      dopaminergic neuroendocrine signals. In this process, the dopaminergic signaling
      appears to be the major pathway because the reduced aversion behavior in cat-2
      mutants and mutants of JNK/MAPK pathway genes was significantly recovered by
      pretreatment with dopamine. RNAi depletion of hsp-16.2, a cytosolic chaperone,
      and cyp-35A family reduced the aversion phenotype, which was further reduced in
      cat-2 mutants, suggesting that dopaminergic signal is indeed dominantly required
      for the caffeine-induced food aversion. Our findings suggest that aversion
      behavior is a defense mechanism for worms to survive under the high-dose caffeine
      conditions. [BMB Reports 2017; 50(1): 31-36].

PMID- 27697106
TI  - GPR78 promotes lung cancer cell migration and metastasis by activation of Galphaq
      Rho GTPase pathway.
AB  - GPR78 is an orphan G-protein coupled receptor (GPCR) that is predominantly
      expressed in human brain tissues. Currently, the function of GPR78 is unknown.
      This study revealed that GPR78 was expressed in lung cancer cells and functioned
      as a novel regulator of lung cancer cell migration and metastasis. We found that
      knockdown of GPR78 in lung cancer cells suppressed cell migration. Moreover,
      GPR78 modulated the formation of actin stress fibers in A549 cells, in a RhoA-
      and Rac1-dependent manner. At the molecular level, GPR78 regulated cell motility
      through the activation of Galphaq-RhoA/Rac1 pathway. We further demonstrated that
      in vivo, the knockdown of GPR78 inhibited lung cancer cell metastasis. These
      findings suggest that GPR78 is a novel regulator for lung cancer metastasis and
      may serve as a potential drug target against metastatic human lung cancer. [BMB
      Reports 2016; 49(11): 623-628].

PMID- 27697107
TI  - C-terminally mutated tubby protein accumulates in aggresomes.
AB  - The tubby protein (Tub), a putative transcription factor, plays important roles
      in the maintenance and function of neuronal cells. A splicing defect-causing
      mutation in the 3'-end of the tubby gene, which is predicted to disrupt the
      carboxy-terminal region of the Tub protein, causes maturity-onset obesity,
      blindness, and deafness in mice. Although this pathological Tub mutation leads to
      a loss of function, the precise mechanism has not yet been investigated. Here, we
      found that the mutant Tub proteins were mostly localized to puncta found in the
      perinuclear region and that the C-terminus was important for its solubility.
      Immunocytochemical analysis revealed that puncta of mutant Tub co-localized with
      the aggresome. Moreover, whereas wild-type Tub was translocated to the nucleus by
      extracellular signaling, the mutant forms failed to undergo such translocation.
      Taken together, our results suggest that the malfunctions of the Tub mutant are
      caused by its misfolding and subsequent localization to aggresomes. [BMB Reports
      2017; 50(1): 37-42].

PMID- 27697108
TI  - Expression and characterization of transmembrane and coiled-coil domain family 3.
AB  - Transmembrane and coiled-coil domain family 3 (TMCC3) has been reported to be
      expressed in the human brain; however, its function is still unknown. Here, we
      found that expression of TMCC3 is higher in human whole brain, testis and spinal
      cord compared to other human tissues. TMCC3 was expressed in mouse developing
      hind brain, lung, kidney and somites, with strongest expression in the mesenchyme
      of developing tongue. By expression of recombinant TMCC3 and its deletion
      mutants, we found that TMCC3 proteins self-assemble to oligomerize.
      Immunostaining and confocal microscopy data revealed that TMCC3 proteins are
      localized in endoplasmic reticulum through transmembrane domains. Based on
      immunoprecipitation and mass spectroscopy data, TMCC3 proteins associate with
      TMCC3 and 14-3-3 proteins. This supports the idea that TMCC3 proteins form
      oligomers and that 14-3-3 may be involved in the function of TMCC3. Taken
      together, these results may be useful for better understanding of uncharacterized
      function of TMCC3. [BMB Reports 2016; 49(11): 629-634].

PMID- 27697109
TI  - Epigenetic regulation of long noncoding RNA UCA1 by SATB1 in breast cancer.
AB  - Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated
      DNA-binding protein that functions as a chromatin organizer. SATB1 is highly
      expressed in aggressive breast cancer cells and promotes growth and metastasis by
      reprograming gene expression. Through genomewide cross-examination of gene
      expression and histone methylation, we identified SATB1 target genes for which
      expression is associated with altered epigenetic marks. Among the identified
      genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was
      upregulated by SATB1 depletion. Upregulation of UCA1 coincided with increased
      H3K4 trimethylation (H3K4me3) levels and decreased H3K27 trimethylation
      (H3K27me3) levels. Our study showed that SATB1 binds to the upstream region of
      UCA1 in vivo, and that its promoter activity increases with SATB1 depletion.
      Furthermore, simultaneous depletion of SATB1 and UCA1 potentiated suppression of
      tumor growth and cell survival. Thus, SATB1 repressed the expression of oncogenic
      UCA1, suppressing growth and survival of breast cancer cells. [BMB Reports 2016;
      49(10): 578-583].

PMID- 27697110
TI  - Oct4 resetting by Aurkb-PP1 cell cycle axis determines the identity of mouse
      embryonic stem cells.
AB  - In embryonic stem cells (ESCs), cell cycle regulation is deeply connected to
      pluripotency. Especially, core transcription factors (CTFs) which are essential
      to maintaining the pluripotency transcription programs should be reset during
      M/G1 transition. However, it remains unknown about how CTFs are governed during
      cell cycle progression. Here, we describe that the regulation of Oct4 by Aurora
      kinase b (Aurkb)/protein phosphatase 1 (PP1) axis during the cell cycle is
      important for resetting Oct4 to pluripotency and cell cycle related target genes
      in determining the identity of ESCs. Aurkb starts to phosphorylate Oct4(S229) at
      the onset of G2/M phase, inducing the dissociation of Oct4 from chromatin,
      whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition,
      which resets Oct4-driven transcription for pluripotency and the cell cycle.
      Furthermore, Aurkb phosphormimetic and PP1 binding-deficient mutations in Oct4
      disrupt the pluripotent cell cycle, lead to the loss of pluripotency in ESCs, and
      decrease the efficiency of somatic cell reprogramming. Based on our findings, we
      suggest that the cell cycle is directly linked to pluripotency programs in ESCs.
      [BMB Reports 2016; 49(10): 527-528].

PMID- 27697113
TI  - Nutritional care of older patients: experiences of general practitioners and
      practice nurses.
AB  - Older people living in the community face unique nutritional issues that put them
      at risk of undernutrition, which is associated with increased morbidity and
      mortality. Primary healthcare staff such as general practitioners (GPs) and
      practice nurses (PNs) are well placed to identify nutritional problems early and
      intervene. The aim of this study was to understand the experiences and current
      practices in a sample of GPs and PNs with regards to nutritional care of elderly
      patients. An online survey of GPs and PNs working in regional Victoria was
      conducted. Among the 45 respondents, 89% reported encountering consultations with
      a nutritional component for older patients within the previous 3 months, and 94%
      of those took some action, most commonly referrals, dietary advice or prescribing
      supplements. Although the majority (63%) felt confident in providing appropriate
      nutritional recommendations for patients, 68% reported a desire for further
      professional development in the area. Given the frequency of nutritional issues
      presenting, further work is required to determine how well equipped primary
      healthcare staff are to provide nutritional advice to older patients.

PMID- 27697112
TI  - Polymer brush: a promising grafting approach to scaffolds for tissue engineering.
AB  - Polymer brush is a soft material unit tethered covalently on the surface of
      scaffolds. It can induce functional and structural modification of a substrate's
      properties. Such surface coating approach has attracted special attentions in the
      fields of stem cell biology, tissue engineering, and regenerative medicine due to
      facile fabrication, usability of various polymers, extracellular matrix (ECM)
      like structural features, and in vivo stability. Here, we summarized polymer
      brush-based grafting approaches comparing self-assembled monolayer (SAM)-based
      coating method, in addition to physico-chemical characterization techniques for
      surfaces such as wettability, stiffness/ elasticity, roughness, and chemical
      composition that can affect cell adhesion, differentiation, and proliferation. We
      also reviewed recent advancements in cell biological applications of polymer
      brushes by focusing on stem cell differentiation and 3D supports/implants for
      tissue formation. Understanding cell behaviors on polymer brushes in the scale of
      nanometer length can contribute to systematic understandings of cellular
      responses at the interface of polymers and scaffolds and their simultaneous
      effects on cell behaviors for promising platform designs. [BMB Reports 2016;
      49(12): 655-661].

PMID- 27697115
TI  - ?

PMID- 27697111
TI  - Probing the diversity of healthy oral microbiome with bioinformatics approaches.
AB  - The human oral cavity contains a highly personalized microbiome essential to
      maintaining health, but capable of causing oral and systemic diseases. Thus, an
      in-depth definition of "healthy oral microbiome" is critical to understanding
      variations in disease states from preclinical conditions, and disease onset
      through progressive states of disease. With rapid advances in DNA sequencing and
      analytical technologies, population-based studies have documented the range and
      diversity of both taxonomic compositions and functional potentials observed in
      the oral microbiome in healthy individuals. Besides factors specific to the host,
      such as age and race/ethnicity, environmental factors also appear to contribute
      to the variability of the healthy oral microbiome. Here, we review bioinformatic
      techniques for metagenomic datasets, including their strengths and limitations.
      In addition, we summarize the interpersonal and intrapersonal diversity of the
      oral microbiome, taking into consideration the recent large-scale and
      longitudinal studies, including the Human Microbiome Project. [BMB Reports 2016;
      49(12): 662-670].

PMID- 27697116
TI  - ?

PMID- 27697117
TI  - [Massivt pneumopericardium hos et nyfodt barn].

PMID- 27697118
TI  - [Plasmapheresis in the treatment of acute pancreatitis associated with severe
      hypertriglyceridaemia].
AB  - Acute pancreatitis can be caused by hypertriglyceridaemia. The treatment includes
      lowering of the blood triglyceride levels. We present a case of a 40-year-old
      woman who was admitted in this condition. She was treated with plasmapheresis,
      which led to a rapid decline of the blood triglyceride levels. The national
      Danish guidelines on treatment of acute pancreatitis do not mention
      plasmapheresis as a method of lowering elevated triglyceride levels. We suggest
      that the guidelines should be revised with attention to this treatment option.

PMID- 27697119
TI  - [Reversal strategies for non-vitamin K antagonist oral anticoagulants].
AB  - Non-vitamin K oral anticoagulants (NOACs) are alternatives to vitamin K
      antagonists and provide consistent anticoagulation with equal or better clinical
      outcome and no need for routine monitoring. Bleeding is a feared complication of
      anticoagulants. Until recently, no specific agent has been available for reversal
      of NOACs. Idarucizumab binds dabigatran for rapid reversal of its activity
      without procoagulant effects. Andexanet alpha (expected release in 2016) and
      PER977 are antidotes under clinical development. This article summarizes current
      and potential future options to antagonize NOACs.

PMID- 27697120
TI  - [Oedematous malnutrition can also be seen in Danish children].
AB  - We describe two children with oedematous malnutrition; one admitted to a
      nutrition unit in Uganda and another to a paediatric department in Denmark. Both
      children received nutritional therapy and recovered. Although oedematous
      malnutrition is rarely seen in industrialized countries, the condition has been
      associated with chronic diseases. It is a life-threatening condition, and the
      pathogenesis remains unknown. Specialized nutrition products have been developed
      for low-resource clinics in developing countries, however, no specific protocols
      or products are available for physicians in Denmark.

PMID- 27697121
TI  - [Penile fracture and testicular rupture must be diagnosed quickly and require
      surgical intervention].
AB  - This article describes penile fracture and testicular rupture and offers
      recommendations for management. Both conditions occur most commonly after blunt
      trauma. Diagnosis can be supported by imaging but is usually confirmed on
      surgical exploration, which in both cases should be carried out promptly. Penile
      fracture occurs most commonly related to coitus, and surgical correction
      decreases the risk of long-term erectile dysfunction, deformity and pain.
      Testicular rupture usually presents with persisting pain and haematoma after
      trauma, and surgery is recommended to minimize permanent organ damage.

PMID- 27697122
TI  - [Kronisk traumatisk diafragmahernie med displacerede abdominalorganer].

PMID- 27697123
TI  - [Clinical presentation and treatment of medication-overuse headache].
AB  - Medication-overuse headache (MOH) is a disabling, costly and often overlooked
      disorder. The prevalence in Denmark is 1.8% equivalent to 80.000-100.000 adults.
      The aim is to increase awareness of clinical presentation and treatment options
      for patients with MOH when encountered in primary care setting, exemplified by
      three representative cases. Clinical presentation of MOH and three treatment
      approaches are discussed. MOH is a chronic disorder which is preventable and
      treatable.

PMID- 27697124
TI  - [Cardiovascular complications following thoracic radiotherapy in patients with
      cancer].
AB  - Cardiovascular complications following thoracic radiotherapy in patients with
      cancer are well described. Advancements in surgery, radiotherapy and systemic
      treatments have led to an increasing number of cancer survivors and thus an
      increasing number of patients with long-term side effects of their cancer
      treatments. This article describes the short- and long-term cardiovascular
      morbidity and mortality following thoracic radiotherapy and further, optimal
      cardiovascular assessments and diagnostic tools in asymptomatic and symptomatic
      patients.

PMID- 27697125
TI  - [Myopathy in a patient during simvastatin and fluconazole treatment].
AB  - A 69-year-old female was admitted due to progressive loss of muscle strength
      following addition of fluconazole to long-term simvastatin treatment.
      Rhabdomyolysis was suspected and both drugs were discontinued. Forced diuresis
      was initiated together with a short course of prednisolone. After 21 weeks the
      patient had regained normal muscle strength and endurance. The favourable course
      and the absence of antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase suggest that the condition was due to interaction between the two
      drugs, which are both metabolized via the CYP3A4 pathway.

PMID- 27697126
TI  - [Diagnostics and treatment of spondylodiscitis].
AB  - Spondylodiscitis, infection of the spine and intervertebral discs, is a rare
      condition with increasing incidence. Early diagnosis can be challenging due to
      the non-specific symptoms such as back pain and fever. Diagnosis is verified by
      MRI. Microbial aetiology is pursued by blood cultures or surgical biopsy,
      however, some cases remain culture-negative. Long-term antibiotic treatment is
      standard of care. Some patients receive surgical treatment. One-year mortality is
      up to 20%. Recently, published data suggest that six weeks of antibiotics equals
      12 weeks in culture-positive cases.

PMID- 27697127
TI  - [The development of a generic guideline for multidisciplinary team conferences in
      Denmark].
AB  - Since 2005 multidisciplinary team conferences (MDT) has been a crucial pivot for
      the Danish national integrated cancer pathways. Despite the formal decision to
      implement MDT-conferences, many aspects of this complex organization have never
      been addressed. In 2014, The Danish Multidisciplinary Cancer Groups (DMCG)
      provided a workgroup with the task of drafting a Danish national guideline for
      keeping MDT-conferences. This article presents the process of the workgroup, the
      background for the final content of the guideline as well as minutes from
      different parts of the guideline.

PMID- 27697128
TI  - Nurse-initiated telephone follow-up on patients with chronic obstructive
      pulmonary disease improves patient empowerment, but cannot prevent readmissions.
AB  - INTRODUCTION: Readmissions reduce quality of life and increase mortality.
      Furthermore, disease severity and shortened length of stay make it difficult to
      support disease management during admission. The aim of this study was to explore
      whether telephone follow-up after discharge may reduce readmission rates, lower
      mortality and improve disease management in patients with chronic obstructive
      pulmonary disease (COPD). METHODS: This was a randomised controlled trial (n =
      224) with nurse-initiated telephone intervention after discharge. On day 30,
      questionnaires about health status and perceptions of disease management were
      completed. Readmission and death were recorded on days 30 and 84. RESULTS: There
      was no significant difference in readmission rates, but significant differences
      in patients' assessment of own perception of managing dyspnoea, lung symptoms,
      ability to react to signs of exacerbation and communicate with health
      professionals. There was a trend towards a higher mortality in the control group,
      but it was not statistically significant. CONCLUSIONS: Nurse-initiated telephone
      follow-up does not reduce readmission rates, but does empower patients with COPD.
      FUNDING: The project was funded in part by the Capital Region of Denmark as part
      of the implementation of The National Plan for Elderly Medical Patients. TRIAL
      REGISTRATION: The Danish Data Protection Agency approved the project (j. no.NOH
      2015-035) and approval was obtained from The Regional Ethics Committee
      (notification number 27518).

PMID- 27697129
TI  - Auditory profiling and hearing-aid satisfaction in hearing-aid candidates.
AB  - INTRODUCTION: Hearing-impaired (HI) listeners often complain about difficulties
      communicating in the presence of background noise, although audibility may be
      restored by a hearing-aid (HA). The audiogram typically forms the basis for HA
      fitting, i.e. people with similar audiograms are given the same prescription by
      default. This study aimed at identifying clinically relevant tests that may serve
      as an informative addition to the audiogram and which may relate more directly to
      HA satisfaction than the audiogram does. METHODS: A total of 29 HI and 26 normal
      hearing listeners performed tests of spectral and temporal resolution, binaural
      hearing, speech intelligibility in stationary and fluctuating noise and a working
      memory test. Six weeks after HA fitting, the HI listeners answered a
      questionnaire evaluating HA treatment. RESULTS: No other measures than masking
      release between fluctuating and stationary noise correlated significantly with
      audibility. The HI listeners who obtained the least advantage from fluctuations
      in background noise in terms of speech intelligibility experienced greater HA
      satisfaction. CONCLUSION: HI listeners have difficulties in different hearing
      domains that are not predictable from their audiogram. Measures of temporal
      resolution or speech perception in both stationary and fluctuating noise could be
      relevant measures to consider in an extended auditory profile. FUNDING: The study
      was supported by Grosserer L.F. Foghts Fond. TRIAL REGISTRATION: The protocol was
      approved by the Science Ethics Committee of the Capital Region of Denmark
      (reference H-3-2013-004).

PMID- 27697130
TI  - Lack of national consensus in preoperative airway assessment.
AB  - INTRODUCTION: Difficult airway management is associated with an increased risk of
      morbidity and mortality. Several preoperative risk factors associated with airway
      management difficulties have been proposed; however, no clear guideline for
      airway assessments exists. We therefore hypothesised that Danish airway
      assessment was lacking uniformity. We aimed to examine whether multivariable risk
      assessment tools and predictors for difficult intubation and mask ventilation
      were used systematically. METHODS: Heads of anaesthesia departments were sent a
      six-question survey at the beginning of 2012. We asked if systematic risk
      assessment tools, particularly the Simplified Airway Risk Index (SARI), and
      predictors for difficult intubation and mask ventilation were used. Additionally,
      we asked if any risk factors were pre-printed on the anaesthesia record. RESULTS:
      In all, 29 of 31 (94%) departments responded. The SARI was implemented in 8 of 29
      (28%, 95% confidence interval (CI): 15-46%) departments with major regional
      differences. There was no significant association between using the SARI and a
      reduced number of unanticipated difficult intubation (p = 0.06). Mallampati
      classification (95.2%, 95% CI: 77.3-99.2%), history of airway management
      difficulties (85.7%, 95% CI: 65.4-95.0%), ability to prognath (81.0%, 95% CI:
      60.0-92.3%) and neck mobility (81.0%, 95% CI: 60.0-92.3%) were the main
      predictors registered. CONCLUSION: We found considerable inter-departmental
      variance in the standards employed for airway assessment and no uniform pattern
      in the registration of risk factors for airway management difficulties. Better
      prediction of difficult intubation could not be detected in departments that used
      the SARI. FUNDING: none. TRIAL REGISTRATION: not relevant.

PMID- 27697131
TI  - Clinical management of acute diabetic Charcot foot in Denmark.
AB  - INTRODUCTION: Charcot foot is a severe complication to diabetes mellitus and
      treatment involves several different clinical specialities. Our objective was to
      describe the current awareness, knowledge and treatment practices of Charcot foot
      among doctors who handle diabetic foot disorders. METHODS: This study is based on
      a questionnaire survey sent out to healthcare professionals, primarily doctors,
      working with diabetic foot ulcers and Charcot feet in the public sector of the
      Danish healthcare system. RESULTS: The survey obtained a 52% response rate. A
      temperature difference of > 2  degrees C between the two feet was the most used
      method of diagnosing Charcot foot. Along with clinical inspection, temperature
      difference was also the measurement used for monitoring of healing. None of the
      suggested formalised classification systems were used to any extent. Most
      responders use detachable bandages for offloading (83%). All centres use some
      form of a multidisciplinary team, with the most common permanent members being
      orthopaedic surgeons (71%), wound specialist nurses (76%), podiatrists (65%),
      endocrinologists (47%) and diabetes specialist nurses (41%). CONCLUSION: We
      conducted a survey of the diagnosis and treatment practices of acute diabetic
      Charcot foot at diabetes foot clinics in Denmark. The responders seem to follow
      the international recommendations and guidelines on management of the acute
      diabetic Charcot foot, despite a lack of Danish guidelines. FUNDING: none. TRIAL
      REGISTRATION: not relevant.

PMID- 27697132
TI  - Observational study identifies non-attendance characteristics in two hospital
      outpatient clinics.
AB  - INTRODUCTION: Non-attended hospital appointments are receiving increasing
      attention in times when rapid access and efficient service delivery at public
      hospitals are on the agenda. The aim of this study was to investigate the extent
      of non-attendance in a Danish outpatient setting and its association with user
      level and provider-level characteristics. METHODS: The study was based on
      appointments scheduled from June 2013 to March 2015 at an orthopaedic and a
      radiologic outpatient clinic. Data on outcomes of cancellation on the part of the
      user or the provider, and non-attendance without giving notice were collected
      from administrative systems along with appointment characteristics. Logistic
      regression was used for statistical analysis. RESULTS: Of the 54,987 and 31,538
      appointments scheduled at the two departments, 4,524 (8%) and 5,479 (17%) were
      cancelled and 2,905 (5%) and 1,249 (4%) were unattended without notice. The
      latter was significantly associated with male gender, younger age and longer time
      since referral. Other characteristics were identified as significant, but
      differed between departments. CONCLUSION: There seems to be a potential for a
      targeted effort aiming to reduce non-attendance and thereby to improve the
      efficiency of Danish outpatient services. Future studies should investigate the
      effect of initiatives such as nudging and fines targeting the appointments that
      have the highest non-attendance rates. FUNDING: Danish Regions, the Danish
      Ministry of Health and the Central Denmark Region funded the study. TRIAL
      REGISTRATION: not relevant.

PMID- 27697133
TI  - Cumulative incidence and registry validation of groin hernia repair in a 34-year
      nationwide cohort.
AB  - INTRODUCTION: The purpose of this study was to present a nationwide cumulative
      incidence and an age-specific incidence rate of groin hernia repair as well as to
      evaluate the validity of inguinal and femoral hernia operation codes in the
      Danish National Patient Registry (DNPR). METHODS: All persons born in Denmark
      from 1977 to 2010 were investigated for groin hernia operations registered in the
      DNPR with respect to date of admission, operation, discharge and specific
      operation codes. To validate the predictive values of registrations, we randomly
      extracted data on elective and emergency groin hernia operations from the DNPR
      from 2005 to 2010 and examined the medical records. RESULTS: The study population
      (n = 2,109,417) from 1977 to 2010 was followed from the primary groin hernia
      operation (n = 53,262) to 2010, yielding a total of 33.4 million person-years of
      follow-up. The probability of being operated for a groin hernia prior to the age
      of 34 years was 5.70% (95% confidence interval (CI): 5.62-5.78) for males and
      1.26% (95% CI: 1.20-1.32) for females. The highest incidence rate was seen among
      males aged 0-1 years (10.19 (95% CI: 10.00-10.38)). The positive predictive value
      of patients registered with inguinal hernia operations in the DNPR who had been
      operated for an inguinal hernia was 100% (95% CI: 96-100%) and 91.3% (95% CI: 83
      96%) for femoral hernia operations. CONCLUSIONS: The incidence rate of groin
      hernia operations peaked at the 0-1 year age group in males and at the 3-4-year
      age group in females. Furthermore, the validation of the DNPR showed very high
      positive predictive values for both inguinal hernia operations and femoral hernia
      operations. FUNDING: none. TRIAL REGISTRATION: not relevant.

PMID- 27697134
TI  - A characterisation of low-grade inflammation and metabolic complications in HIV
      infected patients.
AB  - HIV-associated lipodystrophy syndrome frequently presents as a relative lack of
      peripheral adipose tissue storage combined with an increase in visceral fat,
      associated with insulin resistance and dyslipidaemia. This thesis discusses
      explanations for the links between abnormalities in glucose metabolism, the
      steroid synthesis pathway, the growth hormone-insulin growth factor-1 axis, and
      chronic changes in adipose tissue distribution. Specifically, the mechanisms by
      which low-grade inflammation may affect the normal stimulatory effect of insulin
      on glucose and fat storage are reviewed. We propose that both chronic low-grade
      inflammation from HIV infection and treatment with HAART trigger cellular
      homeostatic stress responses with adverse effects on glucose metabolism. The
      physiological outcome is such that the total energy storage in the adipocytes is
      decreased, and the remaining adipocytes resist further energy storage. The excess
      circulating and dietary lipid metabolites, normally metabolised by adipose
      tissue, are deposited ectopically in the muscle, liver, or visceral adipose
      tissue, where they impair insulin action. This deposition of lipid metabolites
      leads to a vicious circle of insulin resistance and lipotoxicity leading to
      lipoatrophy or a mixed-type with increased visceral adipose tissue and a clinical
      phenotype of HIV-associated lipodystrophy syndrome with an elevated waist-to-hip
      ratio. This HIV-associated inflamm-ageing syndrome can provide a platform for
      further studies in HIV-infected patients and act as a model for biological
      accelerated ageing.

PMID- 27697135
TI  - Risk. Impact of having a first-degree relative with affective disorder: a 7-year
      follow-up study.
AB  - This study investigated a high-risk sample in order to elucidate risk factors for
      affective disorder. Healthy monozygotic (MZ) and dizygotic (DZ) twins with and
      without a co-twin with a history of affective disorder were identified through
      nationwide registers. Two risk groups were identified: the high-risk group
      comprised twins at risk of developing affective disorder (DZ or MZ twin; index co
      twin affected); the low risk group (control group) comprised twins at low risk of
      developing affective disorder (DZ or MZ twin; index co-twin not affected). At
      baseline 234 participants were divided into groups according to their risk for
      affective disorder; they were followed up at 6-month intervals with posted
      questionnaires assessing depression. After a mean follow-up period of 7 years,
      the participants were invited to participate in an individual interview. A total
      of 36 participants (31 high-risk twins and 5 low-risk twins) developed a
      psychiatric disorder during the 7-year follow-up period: 24 developed mood
      disorder (67%), 7 anxiety disorder (19%) and 5 (14%) substance abuse,
      schizophrenia or personality disorder.   The results showed that familial risk,
      impaired stress tolerance and discrete cognitive dysfunction seem to be core
      predictors of affective illness. It is possible to identify a cluster of
      prodromal symptoms encompassing subclinical anxiety and depressive symptoms,
      higher neuroticism and cognitive problems. The cognitive problems may further be
      related to the cross-sectional finding that high-risk twins had lower hippocampal
      volumes. Further, 2 genetic polymorphisms: the 5-HTTLPR and the brain-derived
      neurotrophic factor (BDNF) Val66Met polymorphisms were not directly associated
      with familial risk for affective disorder and did not predict illness onset.
      Similarly, salivary cortisol levels and whole-blood BDNF levels did not predict
      subsequent illness. The more complex 2-way interactions between 5-HTTLPR and life
      events suggested that high-risk individuals and individuals carrying the short s
      allele are exposed to more stressors and that this seems to contribute to an
      overall enhanced risk and thus accelerate the onset of illness. Low-risk
      individuals seem to experience fewer life events and may exhibit resilience to
      their adverse psychological effects. Overall, having a 1st-degree relative with
      affective disorder matters. This thesis demonstrates that high-risk studies are
      informative, allowing observation and investigation of the pathological processes
      that occur prior to the onset of illness. There is a lack of prospective
      intervention studies assessing psychopathology in well-defined, high-risk samples
      and it is obvious that future research must transcend diagnostic boundaries in
      order to have an impact on prevention. Furthermore, there is a need to move
      beyond the notion of ''magic bullets'', instead developing an integrated paradigm
      encompassing clusters of biomarkers related to behavioural measures of
      developmental psychopathology. Finally, as most psychiatric treatment developed
      to date target end-state disorders, the identification of high-risk individuals
      and mapping of individual risk profiles should be a priority in order to
      facilitate early treatment and prevention.

PMID- 27697136
TI  - Childhood depressive disorders.
AB  - Major depressive disorder (MDD) is a frequent and painful mental disorder
      considered among the five leading causes of disability in Western countries by
      the World Health Organization. MDD occurs at all ages, but childhood onset MDD
      has a more severe course with longer depressive episodes, more suicidality, and
      more frequent hospitalization, than later onset MDD. Childhood seems to be a
      window of opportunity for prevention of mental disorders, and subsequently
      prevention of MDD onset in childhood is recommended. Feasible prevention targets
      either individuals who present early signs of a given disorder but have not
      reached diagnostic threshold (indicated prevention) or individuals who are at
      increased risk for a disorder due to risk factor exposure (selective prevention).
      Indicated prevention is rational also for depressive disorders, because
      subthreshold depression (SD) in adults is found to be a precursor to MDD. The
      purpose of this thesis was to provide information necessary for the prevention of
      MDD onset in childhood. First, we examined whether the literature supports that
      SD is a MDD precursor also in children (systematic review). Second, we explored
      the risk that gender might constitute for pre-pubertal and post-pubertal onset
      MDD (register study). Third, we estimated the prevalence of SD and MDD in a large
      scale pre-pubertal sample, and compared the clinical features of SD and MDD and
      potential risk factors (population-based study). The systematic review of the
      literature showed that SD in children and adolescents presents analogous
      comorbidity and symptom patterns (including self-harm symptoms). It also supports
      that SD is a precursor to MDD in children and adolescents causing poor outcomes
      like psychopathology, functional impairment and high use of health service. In
      the register study of Danish children and adolescents, we found a higher
      incidence of clinical MDD for girls after puberty compared to boys. Before
      puberty however, we demonstrated that boys had higher MDD incidence rates than
      girls. The population-based study including 3,421 8-10-year-old children from the
      Danish National Birth Cohort (DNBC) showed point prevalence estimates of 0.5% for
      MDD and 1.0% for SD. Children with SD by definition hold fewer depressive
      symptoms, but the ranking and frequency of these individual depressive symptoms
      was almost similar. Only irritability, anhedonia and worthlessness/guilt were
      more common in children with MDD. DNBC children with SD and MDD had comorbid
      anxiety or conduct/oppositional disorders just as frequently, and the degree of
      functional impairment was the same. When examining potential risk factors for SD
      and MDD, we found that poor general health, more than two stressful life events
      (SLE) within the past year, and a high level of maternal depressive symptoms were
      correlated to both SD and MDD. In addition we found epilepsy/convulsions, one SLE
      within the past year and parental divorce/separation to be correlated to MDD. In
      conclusion, the findings reported in this thesis underline that SD in childhood
      and adolescence is a significant condition calling for attention, due to the
      early onset, the risk for progression into MDD and the poor outcome. Indicated
      prevention aimed at MDD in childhood should target SD children who are
      characterised by fewer depressive symptoms but the same symptom pattern, the same
      level of impairment, and the same amount of comorbid anxiety and
      conduct/oppositional disorders, as presented by children with MDD. Selective
      preventive interventions could effectively target children who suffer from
      chronic physical illness and children whose mothers present depressive symptoms,
      also below clinical threshold. In addition, boys might have an increased risk for
      developing pre-pubertal MDD, but this has to be explored further in non-clinical
      samples. We recommend that more attention is paid to children and adolescents
      with subthreshold depressive symptoms who also pre-sent significant functional
      impairment. Emphasis must be put on the risk for SD transforming into MDD,
      especially in those exposed to the potential risk factors identified in this
      thesis.

PMID- 27697137
TI  - Cancer of the upper rectum.
AB  - Rectal cancer constitutes one-third of all colorectal cancers, and the incidence
      in Denmark increasing. In 2012, 1.400 cases were registered, and of these 38%
      were located in the upper rectum. There have been several key advances in the
      optimal management of rectal cancer during the past decades, primarily by
      standardisation and improvement of the surgical procedure. There is now general
      agreement that the optimal surgical treatment involves the concept of total
      mesorectal excision and that a resection with tumour-free margins is crucial.
      Controversy exists as to whether total mesorectal excision (TME) is necessary for
      upper rectal cancers or if a partial mesorectal excision (PME) with mesorectal
      transection 5 cm below the tumour is adequate. Furthermore, there is no agreement
      as to whether surgery alone is sufficient or whether neoadjuvant radio- and/or
      chemotherapy should be administered for tumours of the upper rectum. This thesis
      aims to discuss aspects of the treatment of rectal cancer with regard to the
      adequacy of mesorectal excision and oncological outcome with a particular focus
      on cancer of the upper rectum. In study I, the extent and completeness of
      mesorectal excision was estimated by postoperative magnetic resonance imaging of
      the pelvis in patients with primary surgery for rectal cancer. In the 136
      patients with post-operative MRI, inadvertent residual mesorectal tissue was
      evident in 40%, especially following PME, suggesting suboptimal surgery
      performed. Additionally in patients who had PME, the distal margin was found to
      be less than 3 cm in more than 50% of patients, suggesting a discrepancy between
      guidelines and the actual surgery performed. In study II, we estimated the risk
      of local recurrence in the previously audited cohort of patients, with a
      particular focus on patients with upper rectal cancer treated by PME and without
      neo-adjuvant therapy as standard. Using Kaplan-Meier analysis, the total three
      year local recurrence rate was 7% with tumour stage and an involved
      circumferential margin as the most important predictors of local recurrence. The
      local recurrence rate after PME was significantly higher than for TME (14% vs.
      3%; p=0.032), and were diagnosed earlier (p=0.001). In all cases with local
      recurrence following PME there was evidence of either inadvertent residual
      mesorectum and/or an insufficient distal resection margin. In study III, we
      investigated the length of the distal resection margin and degree of tissue
      shrinkage after surgical removal and fixation by using MRI of the fresh and fixed
      specimen. We found that the length of the specimen and the distal margin was
      reduced by 30% after surgical removal and fixation. If a 5-cm distal margin below
      the luminal level of the primary tumour on the fresh specimen is the objective
      for advanced cancer of the upper rectum treated with PME surgery, a margin of at
      least 3.5 cm of mesorectum on the fixed specimen should be attained for the
      pathologist to accurately establish distal radicality.

PMID- 27697138
TI  - Acceptance and Commitment Group Therapy (ACT-G) for health anxiety.
AB  - Health anxiety is prevalent (5-9%) in all healthcare settings and in the general
      population, may have an early onset, and a poor prognosis is seen in severe cases
      if untreated. Research shows that health anxiety is rarely diagnosed though it
      causes great suffering for the individual and constitutes a substantial socio
      economic burden. Studies have shown that individual cognitive behavioural therapy
      can relieve health anxiety, but these studies are affected by methodological
      problems, among others, struggling with patients declining participation, high
      dropout rates, and some patients not responding to the treatment. Moreover, the
      impact of health anxiety on sick leave is only scarcely examined. This thesis
      examines the effect of a new treatment approach, group-based Acceptance &
      Commitment Therapy (ACT-G) for patients with severe health anxiety in an
      uncontrolled pilot study and a randomised controlled study (RCT) on ACT-G
      compared with a 10-month waitlist control condition (paper I and II). Also, the
      thesis comprises a study on sick leave in patients with health anxiety compared
      with the general population during a 5-year period and the effect of ACT-G on
      sick leave. The findings from this study are described in paper III. Patients
      (age 20-60 years) consecutively referred from general practitioners from Jutland
      and Funen in the period of March 2010 - April 2012  (approx. 2.5 million
      citizens) to the Research Clinic for Functional Disorders and Psychosomatics,
      Aarhus University Hospital, were included. The pilot study included 34 patients,
      the RCT on ACT-G included 126 patients. In the RCT, patients were block
      randomised to either ACT-G and received treatment in 7 groups of each 9 patients
      in the period of December 2010 - October 2012, or to a 10-month waitlist control
      group. The primary outcome measure was the Whiteley-7 paper and pencil index for
      illness worrying. The last paper is based on data on sickness-related benefits
      from the DREAM social register of transfer benefits and also includes a matched
      general population register control cohort (n=12,600). In this thesis, we wish to
      answer the following questions: 1) Is ACT-G an acceptable, feasible and effective
      treatment approach for patients with severe health anxiety? 2) Can ACT-G improve
      severe illness worry compared with a waitlist control condition, and are the
      recently introduced diagnostic criteria for health anxiety acceptable for the
      patients? 3) Do patients with health anxiety show more sick leave than the
      general population during a 5-year period, and can ACT-G reduce sick leave
      measured by transfer benefits (weeks on sickness-related benefits) at 1-year
      follow-up? As ACT has not previously been examined as treatment approach for
      health anxiety, we initially conducted an uncontrolled pilot study to test the
      newly developed manualised program (ACT-G). The study included 34 patients with
      severe health anxiety and showed very low dropout and high treatment
      satisfaction. Significant improvements in self-reported illness worry were
      demonstrated post-treatment, and the results were sustained and further improved
      at 3- and 6-months follow-up compared to baseline. The subsequent RCT found high
      acceptance of the diagnosis of health anxiety. All patients (except 1) accepted
      the diagnosis as the right diagnosis to fit their ailment, and the majority of
      the patients found that the diagnosis helped them to better understand their
      symptoms. In an intention-to-treat analysis, ACT-G showed significant effect in
      the improvement of self-reported illness worry and other secondary measures
      compared with a waitlist control condition, both post-treatment and at 10-month
      follow-up (6 months post-treatment). The results were considered clinically
      significant as 2/3 of the patients in ACT-G at follow-up had demonstrated a pre
      defined treatment response, and 1/4 of the patients were considered to no longer
      have clinical case status. Furthermore, the number needed to treat was found to
      be 2.4. Patients with severe health anxiety showed significantly more weeks on
      sickness-related benefits than matched individuals from the general population
      during the 5 years prior to entering the RCT. This difference was stable until an
      estimated cut-point at 1 year before enrolment, where patients with health
      anxiety showed further increase in sickness-related-benefits. At one-year follow
      up (8 months post-treatment), we did not find a significant difference between
      ACT-G and the waitlist group in weeks on sickness-related benefits. Post-hoc
      analysis, however, revealed a significant decrease in weeks on sickness-related
      benefits for ACT-G during the 2 years after randomisation. In conclusion, the
      thesis suggests that ACT-G is both an acceptable and effective treatment approach
      for patients with severe health anxiety. Hopefully, these findings can contribute
      to the future research and identification of which treatment approaches are the
      most effective and for which patients and contribute to tailored, early
      interventions. This may possibly prevent development of otherwise chronic
      symptoms, increase the quality of life for the patients, and potentially reduce
      socio-economic costs.

PMID- 27697139
TI  - The analgesic effects of exogenous melatonin in humans.
AB  - The hormone, melatonin is produced with circadian rhythm by the pineal gland in
      humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g.
      blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune
      function and anti-oxidative defence. Interestingly, a number of experimental
      animal studies demonstrate significant dose-dependent anti-nociceptive effects of
      exogenous melatonin. Similarly, recent experimental- and clinical studies in
      humans indicate significant analgesic effects. In study I, we systematically
      reviewed all randomized studies investigating clinical effects of perioperative
      melatonin. Meta-analyses demonstrated significant analgesic and anxiolytic
      effects of melatonin in surgical patients, equating reductions of 20 mm and 19
      mm, respectively on a VAS, compared with placebo. Profound heterogeneity between
      the included studies was, however, present. In study II, we aimed to investigate
      the analgesic, anti-hyperalgesic and anti-inflammatory effects of exogenous
      melatonin in a validated human inflammatory pain model, the human burn model. The
      study was performed as a randomized, double blind placebo-controlled crossover
      study. Primary outcomes were pain during the burn injury and areas of secondary
      hyperalgesia. No significant effects of exogenous melatonin were observed with
      respect to primary or secondary outcomes, compared to placebo. Study III and IV
      estimated the pharmacokinetic variables of exogenous melatonin. Oral melatonin
      demonstrated a tmax value of 41 minutes. Bioavailability of oral melatonin was
      only 3%. Elimination t1/2 were approximately 45 minutes following both oral and
      intravenous administration, respectively. High-dose intravenous melatonin was not
      associated with increased sedation, in terms of simple reaction times, compared
      to placebo. Similarly, no other adverse effects were reported. In Study V, we
      aimed to re-analyse data obtained from a randomized analgesic drug trial by a
      selection of standard statistical test. Furthermore, we presented an integrated
      assessment method of longitudinally measured pain intensity and opioid
      consumption. Our analyses documented that the employed statistical method
      impacted the statistical significance of post-operative analgesic outcomes.
      Furthermore, the novel integrated assessment method combines two interdependent
      outcomes, lowers the risk of type 2 errors, increases the statistical power, and
      provides a more accurate description of post-operative analgesic efficacy.
      Exogenous melatonin may offer an effective and safe analgesic drug. At this
      moment, however, the results of human studies have been contradictory. High
      quality randomized experimental- and clinical studies are still needed to
      establish a "genuine" analgesic effect of the drug in humans. Other perioperative
      effects of exogenous melatonin should also be investigated, before melatonin can
      be introduced for clinical routine use in surgical patients. Despite promising
      experimental and clinical findings, several unanswered questions also relate to
      optimal dosage, timing of administration and administration route of exogenous
      melatonin.

PMID- 27697140
TI  - Individual fertility assessment and counselling in women of reproductive age.
AB  - The overall aim of this thesis was to validate the new concept of the Fertility
      Assessment and Counselling (FAC) Clinic at Rigshospitalet. The intention was to:
      explore the prognostic value of fertility risk factors by a risk score and
      provide an estimate of female fecundity, to quantify the impact of oral
      contraception (OC) on ovarian reserve parameters defined as Anti Mullerian
      Hormone (AMH), Antral Follicle Count (AFC) and ovarian volume, and to gain
      knowledge of attitudes and considerations toward family formation in women of
      advanced age. The thesis is based on the following four manuscripts:   Manuscript
      I describes the predictive value of individual fertility assessment and
      counselling in terms of subsequent time to pregnancy within two years after the
      initial consultation at the FAC Clinic. The follow up study comprised 519 women,
      of which 352 had tried to conceive. At the time of follow-up, 259/352 had
      achieved a pregnancy, 74/352 were still trying and 19/352 had given up. The
      remaining 167 women had no attempts to conceive. The risk assessment provided a
      score based on the appearance of fertility risk factors: green (low), yellow
      (low), orange (medium) and red (high). Two-thirds of the women with only low risk
      scores conceived spontaneously within 12 months (65%), while this figure was only
      32% for women with at least one high risk score (n=82). Accordingly, presence of
      at least one high risk score reduced the odds of achieving a pregnancy within 12
      months by 73% (OR 0.27, 95%CI 0.13-0.57). The FAC Clinic concept seems as a
      usable tool for fertility experts to guide women on how to fulfil their
      reproductive life-plan, but longer follow-up studies are needed. Manuscript II
      describes the impact of OC on ovarian reserve parameters in 887 women at the FAC
      Clinic. Of the 887 women, 244 (27.5%) used OC.  The 244 users of OC were
      significantly younger than non-users with a mean age of 31.5 (SD 4.3) vs. 34.1
      (SD 4.3) years (p < 0.001). Overall, there was no difference between the two
      groups in relation to bodyweight, BMI, smoking habits, gestational age at birth,
      prenatal exposure to maternal smoking or maternal age at menopause. In linear
      regression analyses adjusted for age, ovarian volume was 50% lower, AMH was 19%
      lower, and AFC was 18% lower in OC-users compared to non-users. Among the OC
      users there was a significant decrease in antral follicles sized 5-7 and 8-10 mm
      and an increase in the number of small follicles sized 2-4 mm. Physicians have to
      be aware of the impact of OC use on ovarian reserve parameters and possible
      concealment of premature ovarian insufficiency, when assessing the fertility
      status and estimating the reproductive lifespan in OC users. Manuscript III
      describes the family intentions and personal considerations on postponing
      childbearing in 340 childless women of advanced age. The study comprised 140
      cohabiting and 200 single women aged 35-43 seeking fertility assessment and
      counselling at the FAC Clinic. The majority (82%) was well-educated and in
      employment. Despite their mean age of 37.4 years, the main reasons for attending
      the FAC Clinic were to gain knowledge on the possibility of postponing pregnancy
      (63%) and due to a concern about their fecundity (52%). Both the cohabiting and
      single women expressed a wish for two or more children (60%). The most important
      benefits were "personal development" (89%) and "to give and receive love" (86%).
      The main concerns about childbearing were "less time to myself" (82%) and "less
      time to job and career" (76%). The single women were more positive regarding the
      use of donor sperm (70%) compared to the cohabiting women (25%). Our results
      indicated a general overestimation of the women's own reproductive capacity and
      an underestimation of their risk of future infertility and childlessness with
      continuous postponement of pregnancies. Manuscript IV describes attitudes toward
      family formation in ten single and ten cohabiting childless women of advanced
      age. The women were interviewed one week before their consultation at the FAC
      Clinic about their family formation intentions, considerations and concerns. The
      interviews were analysed and condensed into four categories: ''The biological
      clock'', ''The difficult choice'', ''The dream of the nuclear family'', and
      ''Mother without a father''. The categories were condensed into two subthemes;
      'Fear' and 'Expectations' and gathered into one main theme 'The conflict of
      choosing', which reflected the women's attitudes toward family formation prior to
      individual fertility counselling. The women attended the FAC Clinic due to a
      concern about their fecundity and a fear for infertility. Overall, the women
      expressed a dream of the nuclear family and finding "Mr. Right" and many with the
      wish of buying more time. Both groups would consider solo motherhood due to their
      advanced age, although it was considered to be Plan B, as it was not "natural".

PMID- 27697141
TI  - Follicular T helper cells and IL-21 in rheumatic diseases.
AB  - Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are lifelong
      diseases with increased mortality and chronic pains. They are both characterized
      by immunological imbalances causing the immune system attack and destroy the
      bodies own tissues (called autoimmune disease). The best treatment, we are
      currently able to offer these patients, cause significant side-effects and can
      not prevent significant loss of quality of life. At the heart of the disease
      mechanisms in RA and SLE are subsets of immune cells called T and B cells. These
      cell types produce proteins (called antibodies), which under normal circumstances
      protect the body against disease. In RA and SLE these cells produce antibodies
      that are directed at the bodies own tissues (called autoantibodies), causing
      inflammation and tissue damage. The cause of this loss of tolerance is still
      unknown. Interleukin 21 (IL-21) is thought to exert key functions in controlling
      and directing the T and B cell responses leading to formation of antibodies and
      autoantibodies alike. IL-21 is a signaling molecule secreted by a subpopulation
      of T cells called follicular T helper (Tfh) cells. IFNalpha is another signaling
      molecule of key importance in autoimmune disease. Stratification of SLE patients
      by their responsiveness to IFNalpha has proven a crucial tool in stratifying
      patients in terms of disease development and treatment response. The aim of this
      PhD study is to investigate the role of IL-21 and IFNalpha, and their effects on
      Tfh cells and B cells and the formation of autoantibodies in RA and SLE. The
      first part of this study addresses whether plasma levels of IL-21 influence
      disease activity in rheumatic disease. We further investigate the distribution of
      IL-21-producing Tfh cells in these patients. We find that IL-21 plasma levels
      correlate to disease activity and radiological progression in RA, and that the IL
      21-producing Tfh cell are increased in the blood and synovial fluid of these
      patients. These findings support the idea that IL-21 and Tfh cells are linked to
      the development and perpetuation of these diseases. In the second part of this we
      investigate how small RNA molecules, called microRNAs, can regulate immunological
      processes. We find that microRNA-155 can regulate IL-21's capacity to signal,
      while microRNA-21 is important for survival of T cells. The third, and last part
      of this, concerns IFNalpha signaling and its impact on the development of SLE and
      the formation of autoantibodies. We find that IFNalpha signaling is altered in a
      murine model of SLE, and that inhibition of this signaling pathway leads to
      severe kidney disease. The latter is of key importance as inhibition of IFNalpha
      is currently in early trial as a new treatment form for SLE patients. In SLE
      patients, we find that IFNalpha responsiveness, as measured by a so-called IFN
      signature, is crucial in terms of development of the disease as well as serious
      complications such as kidney disease and involvement of the central nervous
      system. Interferon alpha does this by affecting intracellular signaling responses
      and the formation of autoantibodies. The data presented in this thesis supports
      that IL-21 and Tfh cells have a key role in the disease processes characterizing
      RA and SLE. We further describe a novel mechanism for microRNA-155 and microRNA
      21 in regulating immunological processes in these diseases. Finally we show, that
      IFNalpha has important functions in the formation of autoantibodies in SLE. In
      conclusion, this thesis adds new and important knowledge on the interplay between
      Tfh cells and B cells and their formation of autoantibodies in rheumatic disease.
      This knowledge will guide and further the development of new treatment strategies
      to better patient outcome.

PMID- 27697142
TI  - Resistance in human pathogenic yeasts and filamentous fungi: prevalence,
      underlying molecular mechanisms and link to the use of antifungals in humans and
      the environment.
AB  - Antifungal drug resistance is a multifaceted clinical challenge, and when
      present, a primary cause of treatment failure in patients with severe fungal
      infections. Changing epidemiology, increasing resistance rates and a narrow
      antifungal armamentarium may further underline the required attention on
      resistance particularly within the most prevalent invasive fungal infections
      caused by Candida yeasts and Aspergillus moulds. In Denmark, the resistance
      epidemiology remains to be fully elucidated. This thesis sought to address this
      demand as well as provide insight into the landscape of underlying molecular
      resistance mechanisms. Paper I and II both contributed to the understanding of
      FKS (beta-glucan synthase) mediated echinocandin resistance in Candida species.
      Paper I covered a unique stepwise acquisition of a homozygous mutation in FKS1 of
      Candida tropicalis leading to an amino acid change corresponding to a well-known
      S645P in Candida albicans. Paper II presented a failure case due to Candida
      krusei displaying high-level echinocandin resistance likely attributable to an
      acquired D662Y amino acid substitution in FKS1. Intrinsic differences in FKS1
      among Candida species may explain why the level of resistance both depends on the
      mutation as well as the species and cannot be easily translated to the level of
      clinical resistance. Intrinsic fluconazole resistance in C. krusei further
      substantiated the clinical implications of acquired echinocandin resistance.
      Paper III presented a rare multidrug resistance case in a series of isogenic C.
      albicans isolates, almost covering the entire spectrum of known resistance
      mechanisms in Candida and involved the proposal of novel resistance mutations. An
      A61E change in ERG11 was potentially involved in reduced susceptibility to long
      structured azoles. Increased expression levels of azole efflux pumps were
      probably accredited to novel gain-of-function variants in the transcription
      factor TAC1 (R688Q and R673L). Echinocandin resistance was induced by the well
      known S645P variant of FKS1 and polyene resistance was likely inflicted by a
      frameshift mutation in ERG2 leading to loss of function of the encoded protein
      and subsequent ergosterol depletion. The number of acquired resistance cases is
      increasing in our settings and Paper IV sought to illuminate whether antifungal
      resistance is overlooked in the current fungaemia programme. This involved the
      acquisition of post-treatment oral isolates from 193 candidaemia patients among
      which 114 received azoles (primarily fluconazole) and 85 received an echinocandin
      (and some both). Azole-exposed patients carried a significantly higher proportion
      of species less susceptible to fluconazole (primarily Candida glabrata) among
      colonising Candida compared to baseline blood isolates (p<0.001). A similar trend
      was seen for echinocandin-treated patients although not statistically
      significant. Interestingly, there was a high frequency of acquired resistance,
      29.4% to fluconazole and 21.6% to echinocandins, among colonising C. glabrata
      isolates post treatment. These figures were both significantly higher compared to
      baseline blood isolates as well as oral isolates from patients with no or minimal
      exposure to either drug class. In contrast, acquired resistance among C. albicans
      oral isolates was rare (<5). Thus, the oral cavity may be an unrecognized
      reservoir of resistant Candida species, especially C. glabrata following azole or
      echinocandin treatment. This underlines the care of which therapeutic stewardship
      must be taken both for antifungal naive patients, to avoid resistance
      development, as well as for patients previously exposed to antifungals. Paper V
      presented four fatal cases of invasive aspergillosis involving azole resistant
      Aspergillus fumigatus harbouring resistance mechanisms (TR34/L98H and
      TR46/Y121F/T289A), which are thought to derive from environmental fungicide use.
      The clinical concern is evident because the route of infection is through
      inhalation of potentially azole resistant spores. Still, recent environmental
      surveys were unable to detect azole resistant A. fumigatus in numerous soil
      samples but seasonal variations could be one explanation for this paradox. Paper
      VI was a retrospective laboratory-based study and aimed to elucidate the
      prevalence of azole resistance in A. fumigatus isolates from 2010-2014 in
      Denmark. This study also sought to uncover the underlying resistance mechanisms,
      primarily attributable to CYP51A mutations, and finally to assess the accumulated
      genotyping data. Among 1,162 A. fumigatus isolates, 94.5% were screened for azole
      resistance and a significant increasing trend was observed for the number of
      azole-resistant isolates to approximately 6% in 2014 (p<0.001) and 4% in
      corresponding patients (p<0.05). The underlying resistance mutations were diverse
      but still dominated by the TR34/L98H resistance mechanism responsible for >50% of
      all our azole-resistant isolates. The genotyping data of resistant and a
      selection of susceptible A. fumigatus showed high identity to foreign isolates
      (>15%). This could argue for the hypothesis on clonal expansion, which has
      previously been suggested for TR34/L98H clones in the Netherlands and India, but
      could also indicate an insufficient discriminatory power of such analysis. Still,
      a proposed A. fumigatus outbreak in a haematology ward was unresolved since no
      genetically identical isolates were recovered from patients and air samples,
      illustrating the ubiquitous nature of this organism. Overall, the main concerns
      are a changing Candida epidemiology towards species less susceptible to
      fluconazole combined with the rapid acquisition of echinocandin resistance,
      especially among C. glabrata isolates. For A. fumigatus, the concern is the
      emergence of azole resistant strains in the environment, displaying cross
      resistance to clinical azoles, and thus posing unforeseen clinical challenges in
      the management of invasive aspergillosis. Collectively, these findings call for
      an increased awareness especially at clinical microbiology laboratories, which
      ideally would lead to susceptibility testing of all clinically relevant isolates
      by reference or validated methods. Moreover, novel diagnostic approaches for non
      culturable pathogens are warranted and especially DNA-based detection by PCR may
      serve as a solid complimentary tool for improved diagnostics of invasive fungal
      infections.

PMID- 27697143
TI  - Community-Acquired Pneumonia-an Underestimated Challenge.

PMID- 27697145
TI  - Longitudinal Data Are Needed.

PMID- 27697144
TI  - Pneumonia in the Noninstitutionalized Older Population.
AB  - BACKGROUND: Pneumonia is a common and potentially serious disease, with an
      incidence of ca. 300 per 100 000 persons per year. Until now, there have been
      only a few population-based studies of risk factors for pneumonia. METHODS: From
      2000 to 2002, nearly 10 000 persons aged 50 to 75 were recruited into the
      prospective ESTHER cohort study while visiting their family physician for a check
      up. The mean duration of follow-up was 10.6 years. Data on newly diagnosed
      pneumonia were acquired from the participants and their physicians by means of
      standardized questionnaires. Potential associations with various predictors were
      studied in survival-time regression models. RESULTS: 435 participants had
      pneumonia at least once during follow-up. The cumulative 10-year-incidence was
      4.5% (95% confidence interval [4.0; 4.9]). Multiple regression revealed that age
      (relative risk [RR]: 1.43 [1.22; 1.67] per 10 years), current cigarette smoking
      (RR: 1.56 [1.19; 2.05], compared with never having smoked), and known congestive
      heart failure (RR: 1.65 [1.24; 2.20]) were independently associated with an
      elevated risk of pneumonia. The risk was insignificantly elevated in persons with
      diabetes mellitus (RR: 1.29 [0.98; 1.68]). Alcohol consumption, obesity, stroke,
      and cancer were not associated with an elevated risk of pneumonia in age- and sex
      adjusted analyses. CONCLUSION: Pneumonia plays an important role in the medical
      care of non-institutionalized older people. With the aid of the predictors
      identified in this study, primary care physicians can identify patients at risk,
      smokers can gain additional motivation to quit, treatment compliance can be
      increased, and patients may become more willing to be vaccinated as recommended
      in the current guidelines.

PMID- 27697146
TI  - In Reply.

PMID- 27697147
TI  - The Pharmacological Therapy of Chronic Neuropathic Pain.
AB  - BACKGROUND: Chronic neuropathic pain, including painful peripheral polyneuropathy
      and post-herpetic neuralgia, affects 6.9-10% of the general population. METHODS:
      In this article, we present current treatment recommendations on the basis of a
      selective review of the literature. RESULTS: Neuropathic pain does not respond
      consistently to classic non-opioid analgesic drugs and is better treated with co
      analgesic, antidepressant, and anticonvulsant drugs and topical agents. Under
      certain conditions, however, neuropathic pain can be treated with opioids, even
      chronically. It was concluded in a large-scale m eta- analysis that tricyclic
      antidepressants, selective serotonin- norepinephrine reuptake inhibitors, and
      calcium-channel anticonvulsants are the drugs of first choice, with a number
      needed to treat (NNT) of 3.5-7.7 for a 50% reduction of pain. An analysis of all
      studies yielded an estimated publication bias of 10%. Treatment planning must
      include adequate consideration of the patient's age and comorbidities,
      concomitant medication, and potential side effects. CONCLUSION: Drugs are now
      chosen to treat neuropathic pain independently of the cause and symptoms of the
      pain. Topical agents are used only to treat peripheral neuropathy. The utility of
      a treatment approach based on the patient's symptoms and pathological mechanisms
      was recently demonstrated for the first time in a randomized trial. The goal of
      current research is to facilitate treatment planning on the basis of the clinical
      phenotype.

PMID- 27697149
TI  - Limitations to photosynthesis by proton motive force-induced photosystem II
      photodamage.
AB  - The thylakoid proton motive force (pmf) generated during photosynthesis is the
      essential driving force for ATP production; it is also a central regulator of
      light capture and electron transfer. We investigated the effects of elevated pmf
      on photosynthesis in a library of Arabidopsis thaliana mutants with altered rates
      of thylakoid lumen proton efflux, leading to a range of steady-state pmf extents.
      We observed the expected pmf-dependent alterations in photosynthetic regulation,
      but also strong effects on the rate of photosystem II (PSII) photodamage.
      Detailed analyses indicate this effect is related to an elevated electric field
      (Deltapsi) component of the pmf, rather than lumen acidification, which in vivo
      increased PSII charge recombination rates, producing singlet oxygen and
      subsequent photodamage. The effects are seen even in wild type plants, especially
      under fluctuating illumination, suggesting that Deltapsi-induced photodamage
      represents a previously unrecognized limiting factor for plant productivity under
      dynamic environmental conditions seen in the field.

PMID- 27697148
TI  - The Arabidopsis transcription factor ABIG1 relays ABA signaled growth inhibition
      and drought induced senescence.
AB  - Drought inhibits plant growth and can also induce premature senescence. Here we
      identify a transcription factor, ABA INSENSITIVE GROWTH 1 (ABIG1) required for
      abscisic acid (ABA) mediated growth inhibition, but not for stomatal closure.
      ABIG1 mRNA levels are increased both in response to drought and in response to
      ABA treatment. When treated with ABA, abig1 mutants remain greener and produce
      more leaves than comparable wild-type plants. When challenged with drought, abig1
      mutants have fewer yellow, senesced leaves than wild-type. Induction of ABIG1
      transcription mimics ABA treatment and regulates a set of genes implicated in
      stress responses. We propose a model in which drought acts through ABA to
      increase ABIG1 transcription which in turn restricts new shoot growth and
      promotes leaf senescence. The results have implications for plant breeding: the
      existence of a mutant that is both ABA resistant and drought resistant points to
      new strategies for isolating drought resistant genetic varieties.

PMID- 27697150
TI  - A near atomic structure of the active human apoptosome.
AB  - In response to cell death signals, an active apoptosome is assembled from Apaf-1
      and procaspase-9 (pc-9). Here we report a near atomic structure of the active
      human apoptosome determined by cryo-electron microscopy. The resulting model
      gives insights into cytochrome c binding, nucleotide exchange and conformational
      changes that drive assembly. During activation an acentric disk is formed on the
      central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs
      arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On
      average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one
      catalytic domain may be parked on the hub, when an odd number of zymogens are
      bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per
      active apoptosome. Thus, our structure provides a molecular framework to
      understand the role of the apoptosome in programmed cell death and disease.

PMID- 27697151
TI  - Inhibiting poly(ADP-ribosylation) improves axon regeneration.
AB  - The ability of a neuron to regenerate its axon after injury depends in part on
      its intrinsic regenerative potential. Here, we identify novel intrinsic
      regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and
      poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from
      proteins, act in injured C. elegans GABA motor neurons to enhance axon
      regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate
      DLK function in enhancing axon regeneration. Conversely, PARPs, which add
      poly(ADP-ribose) to proteins, inhibit axon regeneration of both C. elegans GABA
      neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors
      improve axon regeneration when administered after injury. Our results indicate
      that regulation of poly(ADP-ribose) levels is a critical function of the DLK
      regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration
      across species, and that chemical inhibition of PARPs can elicit axon
      regeneration.

PMID- 27697153
TI  - N-Methyl-D-Aspartate Receptors: "C"ing the Culprits Behind Cocaine-Induced
      Metaplasticity.

PMID- 27697152
TI  - NusG inhibits RNA polymerase backtracking by stabilizing the minimal
      transcription bubble.
AB  - Universally conserved factors from NusG family bind at the upstream fork junction
      of transcription elongation complexes and modulate RNA synthesis in response to
      translation, processing, and folding of the nascent RNA. Escherichia coli NusG
      enhances transcription elongation in vitro by a poorly understood mechanism. Here
      we report that E. coli NusG slows Gre factor-stimulated cleavage of the nascent
      RNA, but does not measurably change the rates of single nucleotide addition and
      translocation by a non-paused RNA polymerase. We demonstrate that NusG slows RNA
      cleavage by inhibiting backtracking. This activity is abolished by mismatches in
      the upstream DNA and is independent of the gate and rudder loops, but is
      partially dependent on the lid loop. Our comprehensive mapping of the upstream
      fork junction by base analogue fluorescence and nucleic acids crosslinking
      suggests that NusG inhibits backtracking by stabilizing the minimal transcription
      bubble.

PMID- 27697154
TI  - Modulating Morphine Context-Induced Drug Memory With Deep Brain Stimulation: More
      Research Questions by Lowering Stimulation Frequencies?

PMID- 27697155
TI  - Should Pregnant Women Worry About Caffeine?

PMID- 27697156
TI  - Synaptic Plasticity: The Role of Learning and Unlearning in Addiction and Beyond.

PMID- 27697157
TI  - Chromatin Remodeling in Addiction: BRG1-SMAD3 Interaction Contributes to Cued
      Reinstatement of Cocaine Seeking.

PMID- 27697158
TI  - Pulsed light inactivation of murine norovirus, Tulane virus, Escherichia coli
      O157:H7 and Salmonella in suspension and on berry surfaces.
AB  - Pulsed light (PL) inactivation of two human norovirus (HuNoV) surrogates, murine
      norovirus (MNV-1) and Tulane virus (TV), and two bacterial pathogens, Escherichia
      coli O157:H7 and Salmonella, were evaluated. The viruses and bacteria were
      suspended in phosphate buffered saline (PBS) to final populations of ~6 log
      PFU/mL and ~6 log CFU/mL, respectively. Both viral and bacterial suspensions were
      then irradiated by PL for different durations and the reductions of each
      microorganisms were determined. MNV-1 and TV were significantly (P < 0.05) more
      resistant to PL treatment than Salmonella and E. coli O157:H7 in PBS suspension.
      MNV-1, Salmonella and E. coli O157:H7 were also inoculated on strawberries and
      blueberries and the PL inactivation of each microorganism was determined. Lower
      inactivation of each microorganism was achieved on berry surfaces than in PBS
      suspension. This study shows that PL can induce rapid inactivation of MNV-1, TV,
      Salmonella and E. coli O157:H7 in clear suspension with viruses more resistant to
      PL treatment than bacteria. The efficacy of PL treatment is substantially
      influenced by food surface structure.

PMID- 27697160
TI  - Comparison of three extraction methods to detect noroviruses in dairy products.
AB  - Noroviruses (NoV) are currently the most common cause of viral foodborne diseases
      and RT-qPCR is widely used for their detection in food because of its
      sensitivity, specificity and rapidity. The ISO/TS (15216-1, 15216-2) procedures
      for detecting NoV and HAV in high-risk food categories such as shellfish, bottled
      water and vegetables were published in 2013. Milk products are less implicated in
      foodborne viral outbreaks but they can be contaminated with fruit added to these
      products or by the food handler. Thus, the development of sensitive and reliable
      techniques for the detection of NoV in dairy products is needed to ensure the
      safety of these products. The aim of this study was to develop a RT-qPCR based
      method for the detection of NoV in milk products. Three methods were tested to
      recover NoV from artificially contaminated milk and cottage cheese. The selected
      method was based on the use of proteinase K and the recovery efficiencies ranged
      from 54.87% to 98.87% for NoV GI, 61.16%-96.50% for NoV GII. Murine norovirus and
      mengovirus were used as process controls and their recovery efficiencies were
      respectively 60.59% and 79.23%. The described method could be applied for
      detecting NoV in milk products for routine diagnosis needs.

PMID- 27697159
TI  - Application of phage therapy during bivalve depuration improves Escherichia coli
      decontamination.
AB  - The present study investigated the potential application of the bacteriophage (or
      phage) phT4A, ECA2 and the phage cocktail phT4A/ECA2 to decrease the
      concentration of Escherichia coli during the depuration of natural and
      artificially contaminated cockles. Depuration in static seawater at multiplicity
      of infection (MOI) of 1 with single phage suspensions of phT4A and ECA2 was the
      best condition, as it decreased by ~2.0 log CFU/g the concentration of E. coli in
      artificially contaminated cockles after a 4 h of treatment. When naturally
      contaminated cockles were treated in static seawater with single phage
      suspensions and the phage cocktail, similar decreases in the concentration of E.
      coli (~0.7 log CFU/g) were achieved. However, when employing the phage cocktail,
      a longer treatment time was required to obtain comparable results to those
      achieved when using single phage suspensions. When naturally contaminated cockles
      were depurated with phage phT4A in a recirculated seawater system (mimicking
      industrial depuration conditions), a 0.6 log CFU/g reduction of E. coli was
      achieved after a 2 h of treatment. When the depuration process was performed
      without phage addition, a 4 h treatment was necessary to obtain a similar
      decrease. By combining phage therapy and depuration procedures, a reduction in
      bivalves depuration period can be achieved for, thus decreasing the cost
      associated with this procedure and even enhance the quality and safety of
      depurated bivalves destined for human consumption.

PMID- 27697161
TI  - The influence of dissolved oxygen level and medium on biofilm formation by
      Campylobacter jejuni.
AB  - Campylobacter jejuni survival in aerobic environments has been suggested to be
      mediated by biofilm formation. Biofilm formation by eight C. jejuni strains under
      both aerobic and microaerobic conditions in different broths (Mueller-Hinton
      (MH), Bolton and Brucella) was quantified. The dissolved oxygen (DO) content of
      the broths under both incubation atmospheres was determined. Biofilm formation
      for all strains was highest in MH broth under both incubation atmospheres. Four
      strains had lower biofilm formation in MH under aerobic as compared to
      microaerobic incubation, while biofilm formation by the other four strains did
      not differ under the 2 atm. Two strains had higher biofilm formation under
      aerobic as compared to microaerobic atmospheres in Bolton broth. Biofilm
      formation by all other strains in Bolton, and all strains in Brucella broth, did
      not differ under the 2 atm. Under aerobic incubation DO levels in MH > Brucella >
      Bolton broth. Under microaerobic conditions levels in MH = Brucella > Bolton
      broth. Levels of DO in MH and Brucella broth were lower under microaerobic
      conditions but those of Bolton did not differ under the 2 atm. Experimental
      conditions and especially the DO of broth media confound previous conclusions
      drawn about aerobic biofilm formation by C. jejuni.

PMID- 27697162
TI  - Influence of PDO Ragusano cheese biofilm microbiota on flavour compounds
      formation.
AB  - The objectives of the present study were to characterize the biofilm microbiota
      of 11 different farms (from A to K), producing PDO Ragusano cheese, and to
      investigate on its ability to generate volatile organic compounds (VOCs) in milk
      samples inoculated with biofilm and incubated under Ragusano cheese making
      conditions. The biofilms were subjected to plate counting and PCR/T/DGGE analysis
      and the VOCs generated in incubated milk samples were evaluated through
      SmartNose, GC/O, and GC/MS. Streptococcus thermophilus was the dominant species
      both in biofilms and in incubated milks. Lactobacillus, Lactococcus, Enterococcus
      and Leuconostoc were also identified. Low levels of Pseudomonas spp. and yeasts
      counts were detected, whereas coliforms, Listeria monocytogenes and Salmonella
      spp., were never found. SmartNose and GC/O analyses were able to differentiate
      incubated milk samples on the basis of the odour compounds, highlighting that
      samples E and F overlapped and sample C was clearly separated from the others.
      These results complied with those acquired by GC/MS analysis, that detected in
      total 20 VOCs. Principal component analysis showed positive correlations (r >
      0.6; P < 0.05) between some lactic acid bacteria (LAB) and VOCs: such as
      Enterococcus hirae with alcohols, Lactococcus lactis, Lactobacillus plantarum,
      Lactobacillus casei and Lactobacillus delbrueckii with aldehydes, and
      Lactobacillus fermentum, Lactobacillus helveticus and Lactobacillus hilgardii
      with ketones. This work demonstrates that biofilm represents an excellent source
      of LAB biodiversity, which contribute to generate VOCs during the production of
      PDO Ragusano cheese.

PMID- 27697163
TI  - Cell wall polysaccharides released during the alcoholic fermentation by
      Schizosaccharomyces pombe and S. japonicus: quantification and characterization.
AB  - The present work demonstrates that yeasts belonging to the Schizosaccharomyces
      genus release a high quantity of polysaccharides of cell wall origin starting
      from the onset of the alcoholic fermentation. By the end of the alcoholic
      fermentation, all of the Schizosaccharomyces yeast strains released a quantity of
      polysaccharides approximately 3-7 times higher than that released by a commercial
      Saccharomyces cerevisiae yeast strain under the same fermentative conditions of
      synthetic juice. A higher content of polysaccharide was found in media fermented
      by Schizosaccharomyces japonicus with respect to that of Schizosaccharomyces
      pombe. Some of the strains evaluated were also able to produce high levels of
      pyruvic acid, which has been shown to be an important compound for color
      stability of wine. The presence of strains with different malic acid consumption
      patterns along with high polysaccharide release would enable production of
      naturally modified wines with enhanced mouth feel and reduced acidity. The
      chemical analysis of the released polysaccharides demonstrated divergence between
      the two yeast species S. pombe and S. japonicus. A different mannose/galactose
      ratio and a different percentage of proteins was observed on the polysaccharides
      released by S. pombe as compared to S. japonicus. Analysis of the proteins
      released in the media revealed the presence of a glycoprotein with a molecular
      size around 32-33 kDa only for the species S. japonicus. Mass spectrometry
      analysis of carbohydrate moieties showed similar proportions among the N-glycan
      chains released in the media by both yeast species but differences between the
      two species were also observed. These observations suggest a possible role of
      rapid MALDI-TOF screening of N-glycans compositional fingerprint as a taxonomic
      tool for this genus. Polysaccharides release in the media, in particular
      galactomannoproteins in significant amounts, could make these yeasts particularly
      interesting also for the industrial production of exogenous polysaccharide
      preparations.

PMID- 27697164
TI  - Biodiversity of mycobiota throughout the Brazil nut supply chain: From rainforest
      to consumer.
AB  - A total of 172 Brazil nut samples (114 in shell and 58 shelled) from the Amazon
      rainforest region and Sao Paulo state, Brazil was collected at different stages
      of the Brazil nut production chain: rainforest, street markets, processing plants
      and supermarkets. The mycobiota of the Brazil nut samples were evaluated and also
      compared in relation to water activity. A huge diversity of Aspergillus and
      Penicillium species were found, besides Eurotium spp., Zygomycetes and
      dematiaceous fungi. A polyphasic approach using morphological and physiological
      characteristics, as well as molecular and extrolite profiles, were studied to
      distinguish species among the more important toxigenic ones in Aspergillus
      section Flavi and A. section Nigri. Several metabolites and toxins were found in
      these two sections. Ochratoxin A (OTA) was found in 3% of A. niger and 100% of A.
      carbonarius. Production of aflatoxins B and G were found in all isolates of A.
      arachidicola, A. bombycis, A. nomius, A. pseudocaelatus and A. pseudonomius,
      while aflatoxin B was found in 38% of A. flavus and all isolates of A.
      pseudotamarii. Cyclopiazonic acid (CPA) was found in A. bertholletius (94%), A.
      tamarii (100%), A. caelatus (54%) and A. flavus (41%). Tenuazonic acid, a toxin
      commonly found in Alternaria species was produced by A. bertholletius (47%), A.
      caelatus (77%), A. nomius (55%), A. pseudonomius (75%), A. arachidicola (50%) and
      A. bombycis (100%). This work shows the changes of Brazil nut mycobiota and the
      potential of mycotoxin production from rainforest to consumer, considering the
      different environments which exist until the nuts are consumed.

PMID- 27697165
TI  - Evaluation of different conditions to enhance the performances of Lactobacillus
      pentosus OM13 during industrial production of Spanish-style table olives.
AB  - The main objective was to set up a methodology to improve the high volume
      production of green table olives, cv. Nocellara del Belice. Lactobacillus
      pentosus OM13 was applied during three different industrial processes of table
      olives as follows: trial one (IOP1) was subjected to an addition of lactic acid
      until a brine level of pH 7.0 was reached; trial two (IOP2) subjected to same
      addition of lactic acid as in trial one plus nutrient adjuvant and trial three
      (IOP3) subjected to same addition as trial two, but with the strain L. pentosus
      OM13 acclimatized in brine for 12 h before inoculation. These trials were
      compared against two untreated controls (spontaneously fermented and addition of
      L. pentosus OM13 only). Within the third day of fermentation, the pH of the
      brines decreased significantly, reaching pH 4.85 for trial three, pH 5.15 for
      trial two, and pH 5.92 for trial one. The pH of both controls decreased more
      slowly, and had values below pH 5.0 only after the fifteenth day of fermentation
      (control one) and the sixty-fifth day of fermentation (control two). Trial three
      reached the highest lactic acid bacteria (LAB) concentration on the third day of
      fermentation. After six days of fermentation, all trials showed similar values of
      LAB counts that were significantly higher compared to control number one. The
      result from genotypic identification showed that L. pentosus OM13 was the most
      frequently isolated in the inoculated trials. Lactobacillus plantarum,
      Lactobacillus coryniformis and Pediococcus pentosaceous were also detected at
      very low concentrations. Homoguaiacol, 2-butanol, 4-ethylphenol, phenylethyl
      alcohol and 4-ethylphenol were the volatile organic compounds detected at the
      highest levels in all experimental trials. Trial three showed a higher
      concentration of squalene that was not detected in other trials. The highest
      sensory scores of green olive aroma and overall satisfaction were found for all
      experimental olives, especially for those of trial one and trial two, that
      differed significantly from the untreated controls. This study provides evidence
      that the addition of lactic acid, nutrient adjuvants and, most importantly, the
      acclimatization of LAB cells significantly shortens the acidification process of
      olive brine, and improves safety and sensory quality. Shorter acidification
      processes result in a more rapid transformation of table olives, with reduced
      commodity loss and lower costs of production compared to conventional
      manufacturing protocols.

PMID- 27697166
TI  - Variability in gene content and expression of the thioredoxin system in
      Oenococcus oeni.
AB  - The thioredoxin system protects against oxidative stress through the reversible
      oxidation of the thioredoxin active center dithiol to a disulphide. The genome of
      Oenococcus oeni PSU-1 contains three thioredoxin genes (trxA1, trxA2, trxA3), one
      thioredoxin reductase (trxB) and one ferredoxin reductase (fdr) which, until
      recently, was annotated as a second thioredoxin reductase. For the first time,
      the entire thioredoxin system in several O. oeni strains isolated from wine has
      been analysed. Comparisons at the DNA and protein levels have been undertaken
      between sequences from O. oeni and other genera and species, and the genera
      Leuconostoc and Lactobacillus were found to present the highest similarities. The
      gene most frequently absent from a collection of 34 strains and the sequences
      annotated in the NCBI database was trxA1. Moreover, phylogenetic analysis
      suggested that this gene was horizontally transferred from Lactobacillus to O.
      oeni. Strain-dependent expression profiles were determined in rich and in wine
      like media. General over-expression was detected after inoculation into wine-like
      medium, with trxA3 being the most highly expressed gene. The increased
      transcriptional levels of the thioredoxin genes are indicative of the crucial
      role of this system in the O. oeni response to wine harsh conditions.

PMID- 27697167
TI  - Advances in the genomics and metabolomics of dairy lactobacilli: A review.
AB  - The Lactobacillus genus represents the largest and most diverse genera of all the
      lactic acid bacteria (LAB), encompassing species with applications in industrial,
      biotechnological and medical fields. The increasing number of available
      Lactobacillus genome sequences has allowed understanding of genetic and metabolic
      potential of this LAB group. Pangenome and core genome studies are available for
      numerous species, demonstrating the plasticity of the Lactobacillus genomes and
      providing the evidence of niche adaptability. Advancements in the application of
      lactobacilli in the dairy industry lie in exploring the genetic background of
      their commercially important characteristics, such as flavour development
      potential or resistance to the phage attack. The integration of available genomic
      and metabolomic data through the generation of genome scale metabolic models has
      enabled the development of computational models that predict the behaviour of
      organisms under specific conditions and present a route to metabolic engineering.
      Lactobacilli are recognised as potential cell factories, confirmed by the
      successful production of many compounds. In this review, we discuss the current
      knowledge of genomics, metabolomics and metabolic engineering of the prevalent
      Lactobacillus species associated with the production of fermented dairy foods. In
      depth understanding of their characteristics opens the possibilities for their
      future knowledge-based applications.

PMID- 27697168
TI  - Artisanal Italian salami and soppresse: Identification of control strategies to
      manage microbiological hazards.

PMID- 27697169
TI  - The microbiology of beef carcasses and primals during chilling and commercial
      storage.
AB  - The primary objective of this study was to characterise (microbiology and
      physical parameters) beef carcasses and primals during chilled storage. A minor
      aim was to compare observed growth of key spoilage bacteria on carcasses with
      that predicted by ComBase and the Food Safety Spoilage Predictor (FSSP). Total
      viable count (TVC), total Enterobacteriacae count (TEC), Pseudomonas spp., lactic
      acid bacteria (LAB), Brochothrix thermosphacta and Clostridium spp. were
      monitored on beef carcasses (n = 30) and primals (n = 105) during chilled storage
      using EC Decision 2001/471/EC and ISO sampling/laboratory procedures. The surface
      and/or core temperature, pH and water activity (aw) were also recorded.
      Clostridium (1.89 log10 cfu/cm2) and Pseudomonas spp. (2.12 log10 cfu/cm2) were
      initially the most prevalent bacteria on carcasses and primals, respectively. The
      shortest mean generation time (G) was observed on carcasses with Br.
      thermosphacta (20.3 h) and on primals with LAB (G = 68.8 h) and Clostridium spp.
      (G = 67 h). Over the course of the experiment the surface temperature decreased
      from 37  degrees C to 0  degrees C, pH from 7.07 to 5.65 and aw from 0.97 to 0.93
      The observed Pseudomonas spp. and Br. thermosphacta growth was more or less
      within the range of predictions of Combase. In contrast, the FSSP completely
      overestimated the growth of LAB. This study contributes to the very limited
      microbiological data on beef carcasses and primals during chilling.

PMID- 27697170
TI  - Bacterial microbiota profile in gills of modified atmosphere-packaged oysters
      stored at 4  degrees C.
AB  - As filter-feeding bivalves, oysters can accumulate microorganisms into their
      gills, causing spoilage and potential safety issues. This study aims to
      investigate the changes in the gill microbiota of oysters packed under air and
      modified atmospheres (MAs, 50% CO2: 50% N2, 70% CO2: 30% O2, and 50% CO2: 50% O2)
      during storage at 4  degrees C. The diversity of bacterial microbiota in oyster
      gills was profiled through polymerase chain reaction-denaturing gradient gel
      electrophoresis (PCR-DGGE) analysis on the 16S rRNA gene V3 region to describe
      the variation during the entire storage period. The DGGE profile revealed high
      bacterial diversity in the air- and MA-packaged oyster gills, and the spoilage
      bacterial microbiota varied in the MA-packaged oyster gills. Results indicated
      that CO2:O2 (70%:30%) was suitable for oyster MA packaging and that high
      bacterial loads in oyster gills need to be considered during storage. In
      addition, Lactobacillus and Lactococcus species were found to grow dominantly in
      fresh oyster gills under MA packaging, which supports the potential application
      of MA packaging for oyster storage.

PMID- 27697171
TI  - Survival of Streptococcus suis, Streptococcus dysgalactiae and Trueperella
      pyogenes in dry-cured Iberian pork shoulders and loins.
AB  - Dry-cured hams, shoulders and loins of Iberian pigs are highly appreciated in
      national and international markets. Salting, additive addition and dehydration
      are the main strategies to produce these ready-to-eat products. Although the dry
      curing process is known to reduce the load of well-known food borne pathogens,
      studies evaluating the viability of other microorganisms in contaminated pork
      have not been performed. In this work, the efficacy of the dry curing process to
      eliminate three swine pathogens associated with pork carcass condemnation,
      Streptococcus suis, Streptococcus dysgalactiae and Trueperella pyogenes, was
      evaluated. Results of this study highlight that the dry curing process is a
      suitable method to obtain safe ready-to-eat products free of these
      microorganisms. Although salting of dry-cured shoulders had a moderate
      bactericidal effect, results of this study suggest that drying and ripening were
      the most important stages to obtain dry-cured products free of these
      microorganisms.

PMID- 27697172
TI  - Prokaryotic community composition in alkaline-fermented skate (Raja pulchra).
AB  - Prokaryotes were extracted from skates and fermented skates purchased from fish
      markets and a local manufacturer in South Korea. The prokaryotic community
      composition of skates and fermented skates was investigated using 16S rRNA
      pyrosequencing. The ranges for pH and salinity of the grinded tissue extract from
      fermented skates were 8.4-8.9 and 1.6-6.6%, respectively. Urea and ammonia
      concentrations were markedly low and high, respectively, in fermented skates
      compared to skates. Species richness was increased in fermented skates compared
      to skates. Dominant and predominant bacterial groups present in the fermented
      skates belonged to the phylum Firmicutes, whereas those in skates belonged to
      Gammaproteobacteria. The major taxa found in Firmicutes were Atopostipes
      (Carnobacteriaceae, Lactobacillales) and/or Tissierella (Tissierellaceae,
      Tissierellales). A combination of RT-PCR and pyrosequencing for active bacterial
      composition showed that the dominant taxa i.e., Atopostipes and Tissierella, were
      active in fermented skate. Those dominant taxa are possibly marine lactic acid
      bacteria. Marine bacteria of the taxa Lactobacillales and/or Clostridia seem to
      be important in alkaline fermentation of skates.

PMID- 27697173
TI  - Effect of bioaugmented inoculation on microbiota dynamics during solid-state
      fermentation of Daqu starter using autochthonous of Bacillus, Pediococcus,
      Wickerhamomyces and Saccharomycopsis.
AB  - Daqu, a traditional fermentation starter that is used for Chinese liquor and
      vinegar production, is still manufactured through a traditional spontaneous solid
      state fermentation process with no selected microorganisms are intentionally
      inoculated. The aim of this work was to analyze the microbiota dynamics during
      the solid-state fermentation process of Daqu using a traditional and bioaugmented
      inoculation with autochthonous of Bacillus, Pediococcus, Saccharomycopsis and
      Wickerhamomyces at an industrial scale. Highly similar dynamics of
      physicochemical parameters, enzymatic activities and microbial communities were
      observed during the traditional and bioaugmented solid-state fermentation
      processes. Both in the two cases, groups of Streptophyta, Rickettsiales and
      Xanthomonadales only dominated the first two days, but Bacillales and Eurotiales
      became predominant members after 2 and 10 days fermentation, respectively.
      Phylotypes of Enterobacteriales, Lactobacillales, Saccharomycetales and Mucorales
      dominated the whole fermentation process. No significant difference (P > 0.05) in
      microbial structure was observed between the traditional and bioaugmented
      fermentation processes. However, slightly higher microbial richness was found
      during the bioaugmented fermentation process after 10 days fermentation. Our
      results reinforced the microbiota dynamic stability during the solid-state
      fermentation process of Daqu, and might aid in controlling the traditional Daqu
      manufacturing process.

PMID- 27697174
TI  - Postharvest biocontrol ability of killer yeasts against Monilinia fructigena and
      Monilinia fructicola on stone fruit.
AB  - The antagonistic effects of Debaryomyces hansenii KI2a, D. hansenii MI1a and
      Wickerhamomyces anomalus BS91 were tested against Monilinia fructigena and
      Monilinia fructicola in in vitro and in vivo trials. All yeast strains
      demonstrated antifungal activity at different levels depending on species, strain
      and pathogen. D hansenii KI2a and W. anomalus BS91 showed the highest biocontrol
      activity in vitro; the production of hydrolytic enzymes, killer toxins and
      volatile organic compounds (VOCs) were hypothesized as their main mechanisms of
      action against pathogens. D hansenii KI2a and W. anomalus BS91 significantly
      reduced brown rot incidence and severity on peach and plum fruits artificially
      inoculated with M. fructigena and M. fructicola, especially when applied 24 h
      before pathogen inoculation. On the opposite, D. hansenii MI1a exhibited weak
      antagonistic activity towards M. fructigena on peach and plum fruits and was
      ineffective against M. fructicola. The noticeable ability of W. anomalus BS91 to
      control brown rot could be also correlated with its high capacity to colonize the
      wound tissue and to increase its population density. Accordingly, the
      antagonistic strains of D. hansenii and W. anomalus could be proposed as active
      ingredients for the development of biofungicides against Monilinia species that
      are responsible for considerable economic losses in stone fruit crops.

PMID- 27697175
TI  - Arthroscopic and Related Surgeons and Scientists Are Devoted in Their Service.

PMID- 27697176
TI  - Authors' Reply.

PMID- 27697177
TI  - Regarding "Arthroscopic Posterior Subtalar Arthrodesis: Surgical Technique".

PMID- 27697178
TI  - Editorial Commentary: Can It Really Be That Simple? Predicting Risk Factors for
      Failed Arthroscopic Rotator Cuff Repair.
AB  - Failure after arthroscopic rotator cuff repair is multifactorial. Tear size and
      chronicity do matter but, until a case series with a large enough sample size can
      be performed, we must still continue to counsel patients that a wide variety of
      risk factors and comorbidities may affect healing.

PMID- 27697179
TI  - Editorial Commentary: The Not So Benign Nature of an Isolated SLAP Repair.
AB  - Although superior labrum anterior posterior (SLAP) repairs have a relatively high
      success rate, emerging evidence suggests that this is not always the case. The
      authors of "Subsequent Shoulder Surgery Following Isolated Arthroscopic SLAP
      Repair" reveal that 1 in 10 people needed additional surgery within 3 years after
      SLAP repair-mainly for disorders of the rotator cuff, biceps, and distal
      clavicle. This underscores the fact that SLAP tears rarely occur in isolation and
      that the initial diagnosis and management may require more than just SLAP work.

PMID- 27697180
TI  - Editorial Commentary: Not for The Faint of Heart: The Arthroscopic Latarjet
      Procedure, A North American Experience.
AB  - The Latarjet operation is a very difficult operation both when performed
      arthroscopically and when performed with an open approach. I do not think that
      this is an operation that should be done by a casual shoulder surgeon. I think,
      in the best interests of the patient, that this surgery should be performed only
      by orthopaedic surgeons who are trained in it.

PMID- 27697181
TI  - Editorial Commentary: Can Passive Muscle Stiffness in a Cadaveric Study Be
      Clinically Related to Using Knotted Versus Knotless Rotator Cuff Repair?
AB  - Is a biomechanical cadaveric study to assess the effect of rotator cuff tear size
      and repair technique on supraspinatus muscle stiffness clinically relevant? A
      study in this issue compared double-row and knotless transosseous-equivalent
      repairs, but notably, muscle loading was not simulated. Results showed that the
      knotless transosseous-equivalent repair for larger tears demonstrated a more
      uniform stiffness distribution across the supraspinatus muscle compared with the
      double-row repair. However, given the inherently asymmetrical functional anatomy
      and morphology of the supraspinatus tendon-muscle unit, when muscle tone exists,
      the effect of the repair technique on muscle stiffness in vivo may not be
      determined based on the findings of this study.

PMID- 27697182
TI  - Editorial Commentary: Selection of Graft Attachment Site in Anterolateral
      Ligament Reconstruction.
AB  - When considering the femoral attachment location for an anterolateral ligament
      reconstruction, the femoral attachment site should be positioned proximally and
      posteriorly to the lateral epicondyle to restore the physiologic length change of
      the native ligament. However, the clinical significance of the anterolateral
      ligament in patients having anterior cruciate ligament reconstructive surgery
      remains controversial.

PMID- 27697183
TI  - Editorial Commentary: New Perspectives on the Intra-articular Use of Local
      Anesthetics: Five Weekly Injections of 0.5% Bupivacaine Does Not Alter Articular
      Cartilage.
AB  - Intra-articular injection of 0.5% bupivacaine repeated once a week for 5
      consecutive weeks might not have deleterious effects on either normal or
      osteoarthritic knee joints. The chondrotoxic effect of local anesthetics
      previously reported on in vitro studies was not confirmed by in vivo observations
      on an animal model.

PMID- 27697184
TI  - Editorial Commentary: Addressing the Anterolateral Side of an Anterior Cruciate
      Ligament-Deficient Knee: The Controversy Is Getting Even More Interesting.
AB  - Evidence is building to support consideration of anterolateral knee
      reconstruction in the anterior cruciate ligament-deficient knee with a high-grade
      pivot shift or participation in a high-risk sport. As the pendulum swings back to
      the future with the extra-articular augmentation, our anticipation should be
      tempered by cautious interpretation of the results as the controversy unfolds.

PMID- 27697185
TI  - Editorial Commentary: The Value of Retensioning and Knot Tying.
AB  - This basic science study evaluated the effects of retensioning and knot tying on
      the biomechanical properties of an adjustable-loop anterior cruciate ligament
      reconstruction device compared with a closed-loop device. The authors of a study
      in this issue compared various loading conditions to reveal that retensioning and
      knot tying combine to make both the closed-loop device and the newer adjustable
      loop device clinically equal with regard to cyclic elongation.

PMID- 27697186
TI  - Editorial Commentary: Google It!-Reliability of Medical Information Found on the
      Internet.
AB  - Patients use Google or other search engines to obtain information on various
      medical problems. This information is not always reliable, and physicians should
      direct patients to Web sites that are validated and reliable.

PMID- 27697187
TI  - Editorial Commentary: Knee Focal Cartilage Defect Treatment Must Be
      Individualized.
AB  - Knee focal cartilage treatment depends on many variables including lesion size,
      location, age, and patient activity level. High level of evidence meta-analysis
      suggests that the osteochondral autograft transfer system is superior to
      microfracture for larger lesions and osteochondritis dissecans, but cartilage
      restoration indications must be individualized based on additional variables.

PMID- 27697188
TI  - Editorial Commentary: Knee Cartilage Treatment Literature Rarely Reports Relevant
      Patient Outcomes in a Comprehensive Manner.
AB  - Variable reporting of relevant clinical outcomes results in reporting bias,
      making it difficult to compare and contrast the results of different studies and
      treatments. Cartilage researchers should use the metric reporting score to ensure
      that outcome is reported in a standard manner.

PMID- 27697189
TI  - Editorial Commentary: Limited Data Shows How Little We Know.
AB  - Lateral compartment osteoarthritis of the knee can be a challenging problem to
      address in the younger, active population. The challenge is compounded by limited
      treatment options and high patient expectations, with patients often desiring a
      return to impact high intensity activity. Distal femoral osteotomy has been
      reported to be one potential treatment option; however, a highly heterogeneous
      literature exists for both opening and closing wedge distal femoral osteotomies
      for the treatment of isolated lateral compartment osteoarthritis with valgus
      malalignment. The literature does not provide significant direction for surgeons
      on the appropriate surgical approach; however, opening wedge osteotomies allow
      for fine adjustment and maintain leg length and joint alignment, and are our
      preferred approach.

PMID- 27697190
TI  - Editorial Commentary: Chondrocytes Trump Ligaments! Partial Release of the Medial
      Collateral Ligament During Knee Arthroscopy Protects Chondrocytes.
AB  - With knee arthroscopy being the most common orthopaedic procedure performed in
      the United States, it is crucial to be able to access the entire knee without
      iatrogenic injury. Frequently orthopaedic surgeons encounter tight medial
      compartments, creating difficulty in accessing the posterior horn of the medial
      meniscus without damaging the articular cartilage. Partial release of the medial
      collateral ligament during knee arthroscopy protects chondrocytes.

PMID- 27697191
TI  - Life Lessons, Leadership, and Enduring Friendships.

PMID- 27697192
TI  - The Arthroscopy Association of North America Advanced Arthroscopy Traveling
      Fellowship: A 10-Year History.
AB  - In its brief 10-year existence, the Arthroscopy Association of North America
      Advanced Arthroscopy Traveling Fellowship has quickly established itself as the
      paramount educational experience for aspiring young surgeons in sports medicine
      and arthroscopy. The Traveling Fellowship is structured as a 10-day experience
      with visits to 3 host sites and culminates at the AANA Annual Meeting. With 4
      selected fellows and an honorary "Godfather," the Traveling Fellowship affords a
      unique and invaluable opportunity to forge enduring friendships and rare
      mentorships with established leaders in the field of Arthroscopy. Potential
      applicants can anticipate not only developing their surgical acumen and aspects
      of clinical practice, but also assimilating key leadership skills, pearls on work
      life balance, and a broader commitment to life-long education. The Dr. Don
      Johnson AANA Traveling Fellowship Alumni Group, named in honor of the two-time
      godfather and AANA Past President, represent an emerging class of leaders within
      AANA who are poised to contribute immensely to its mission of continuing medical
      education and collaboration.

PMID- 27697193
TI  - Outcomes after repeat hepatic resection for recurrent metastatic colorectal
      cancer: A population-based study.
AB  - BACKGROUND: More than half of the patients undergoing resection for colorectal
      cancer liver metastases develop recurrent hepatic disease. We report management
      and outcomes of patients undergoing repeat hepatectomy in routine practice.
      METHODS: All cases of repeat hepatectomy for colorectal cancer liver metastases
      from 2002 to 2009 in the Canadian Province of Ontario were identified using the
      population-based Ontario Cancer Registry and linked treatment records. RESULTS:
      Of 1,310 patients who underwent resection of CRLM, 78 (6.0%) underwent a repeat
      liver resection. Mean age was 56 years and the median time between resections was
      19 months. Compared with the first resection, second resections were associated
      with fewer lesions (2.7 vs 1.5; P = .001) and fewer major resections (58% vs 31%;
      P = .024). The size of largest lesion, positive margin rate, length of hospital
      stay, and 90-day mortality were similar. Unadjusted 5-year overall survival from
      the time of second resection was 45% (95% confidence interval = 32% to 59%) and
      cancer-specific survival was 47% (95% confidence interval = 30% to 64%).
      CONCLUSIONS: Repeat liver resections for metastatic CRC involve fewer lesions and
      less extensive surgery and a substantial proportion of patients achieve long-term
      survival.

PMID- 27697194
TI  - Exophytic Tumor on the Left Temple.

PMID- 27697195
TI  - Filiform Follicular Hyperkeratosis on the Face.

PMID- 27697196
TI  - Bermuda Triangle: Coronary Artery Disease, Anxiety Disorders, and Atrial
      Fibrillation.

PMID- 27697197
TI  - A Patient With Alcoholic Ketoacidosis and Profound Lactemia.
AB  - BACKGROUND: Alcoholic ketoacidosis (AKA) is a complex syndrome that results from
      disrupted metabolism in the setting of excessive alcohol use and poor oral
      intake. Dehydration, glycogen depletion, high redox state, and release of stress
      hormones are the primary factors producing the characteristic anion gap metabolic
      acidosis with an elevated beta-hydroxybutyrate (beta-OH) and lactate. CASE
      REPORT: We present the case of a 47-year-old man who presented to the emergency
      department with metabolic acidosis and profoundly elevated lactate levels who had
      AKA. He recovered completely with intravenous fluids and parenteral glucose
      administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency
      physicians should always consider the immediately life-threatening causes of a
      severe anion gap metabolic acidosis and treat aggressively based on the
      situation. This case highlights the fact that AKA can present with an
      impressively elevated lactate levels. Emergency physicians should keep AKA in the
      differential diagnosis of patients who present with a similar clinical picture.

PMID- 27697198
TI  - A Practical Approach to the Ethanol-Intoxicated Patient in the Emergency
      Department.

PMID- 27697199
TI  - Masquelet technique for the treatment of segmental bone loss have we made any
      progress?

PMID- 27697200
TI  - Mouse Models of Gonadotrope Development.
AB  - The pituitary gonadotrope is central to reproductive function. Gonadotropes
      develop in a systematic process dependent on signaling factors secreted from
      surrounding tissues and those produced within the pituitary gland itself. These
      signaling pathways are important for stimulating specific transcription factors
      that ultimately regulate the expression of genes and define gonadotrope identity.
      Proper gonadotrope development and ultimately gonadotrope function are essential
      for normal sexual maturation and fertility. Understanding the mechanisms
      governing differentiation programs of gonadotropes is important to improve
      treatment and molecular diagnoses for patients with gonadotrope abnormalities.
      Much of what is known about gonadotrope development has been elucidated from
      mouse models in which important factors contributing to gonadotrope development
      and function have been deleted, ectopically expressed, or modified. This chapter
      will focus on many of these mouse models and their contribution to our current
      understanding of gonadotrope development.

PMID- 27697201
TI  - Clinical Applications of Gonadotropins in the Male.
AB  - The pituitary gonadotropins, luteinizing hormone (LH), and follicle-stimulating
      hormone (FSH) play a pivotal role in reproduction. The synthesis and secretion of
      gonadotropins are regulated by complex interactions among several endocrine,
      paracrine, and autocrine factors of diverse chemical structure. In men, LH
      regulates the synthesis of androgens by the Leydig cells, whereas FSH promotes
      Sertoli cell function and thereby influences spermatogenesis. Gonadotropins are
      complex molecules composed of two subunits, the alpha- and beta-subunit, that are
      noncovalently associated. Gonadotropins are decorated with glycans that regulate
      several functions of the protein including folding, heterodimerization,
      stability, transport, conformational maturation, efficiency of heterodimer
      secretion, metabolic fate, interaction with their cognate receptor, and selective
      activation of signaling pathways. A number of congenital and acquired
      abnormalities lead to gonadotropin deficiency and hypogonadotropic hypogonadism,
      a condition amenable to treatment with exogenous gonadotropins. Several natural
      and recombinant preparations of gonadotropins are currently available for
      therapeutic purposes. The difference between natural and the currently available
      recombinant preparations (which are massively produced in Chinese hamster ovary
      cells for commercial purposes) mainly lies in the abundance of some of the
      carbohydrates that conform the complex glycans attached to the protein core.
      Whereas administration of exogenous gonadotropins in patients with isolated
      congenital hypogonadotropic hypogonadism is a well recognized therapeutic
      approach, their role in treating men with normogonadotropic idiopathic
      infertility is still controversial. This chapter concentrates on the main
      structural and functional features of the gonadotropin hormones and how basic
      concepts have been translated into the clinical arena to guide therapy for
      gonadotropin deficit in males.

PMID- 27697202
TI  - Beyond Reproduction: Pituitary Hormone Actions on Bone.
AB  - The long-held belief that pituitary hormones act solely on master targets was
      first questioned when we documented G protein-coupled receptors for thyroid
      stimulating hormone, follicle-stimulating hormone, adrenocorticotrophic hormone,
      oxytocin, and vasopressin on bone cells. These evolutionarily conserved hormones
      and their receptors are known to have primitive roles, and exist in invertebrate
      species as far down as coelenterates. It is not surprising therefore that each
      such hormone has multiple hitherto unrecognized functions in mammalian
      integrative physiology, and hence, becomes a potential target for therapeutic
      intervention. Here we discuss the skeletal actions of pituitary hormones.

PMID- 27697203
TI  - Gonadotrope Tumors.
AB  - Gonadotrope tumors arise from the gonadotropes of the adenohypophysis. These
      cells rarely give rise to hyperplasia, usually only in the setting of long
      standing premature gonadal failure. In contrast, gonadotrope tumors represent one
      of the most frequent types of pituitary tumors. Despite their relatively common
      occurrence, the pathogenesis of gonadotrope tumors remains unknown. Effective
      nonsurgical therapies remain out of reach. We review the pituitary gonadotrope
      from the morphologic and functional perspectives to better understand its
      involvement as the cell of origin of a frequent type of pituitary tumor.

PMID- 27697204
TI  - Mouse Models for the Study of Synthesis, Secretion, and Action of Pituitary
      Gonadotropins.
AB  - Gonadotropins play fundamental roles in reproduction. More than 30years ago, Cga
      transgenic mice were generated, and more than 20years ago, the phenotypes of Cga
      null mice were reported. Since then, numerous mouse strains have been generated
      and characterized to address several questions in reproductive biology involving
      gonadotropin synthesis, secretion, and action. More recently, extragonadal
      expression, and in some cases, functions of gonadotropins in nongonadal tissues
      have been identified. Several genomic and proteomic approaches including novel
      mouse genome editing tools are available now. It is anticipated that these and
      other emerging technologies will be useful to build an integrated network of
      gonadotropin signaling pathways in various tissues. Undoubtedly, research on
      gonadotropins will continue to provide new knowledge and allow us transcend from
      benchside to the bedside.

PMID- 27697206
TI  - Preface.

PMID- 27697205
TI  - Clinical Applications of Gonadotropins in the Female: Assisted Reproduction and
      Beyond.
AB  - Gonadotropins (LH, FSH, and hCG) act in concert in the regulation of female
      reproductive system. Exploiting this influence, they are part of the assisted
      reproductive technique protocols. In this review we analyze the effectiveness of
      the different available gonadotropin formulations and the consequent adverse
      events. Moreover, different protocols for poor-responders and polycystic ovary
      syndrome affected women are explored. All these clinical different approaches
      have specific molecular bases, covered in this review starting from evolution and
      population genetics, getting to in vitro studies of gonadotropins action. Beyond
      their application in assisted reproductive technique, gonadotropins have also
      been largely studied for their intertwined network of interactions with other
      hormones, which all together contribute to the functioning of the reproductive
      system and other hormonal axes. In particular, there is both clinical and
      molecular evidence of interaction between thyroid hormones and insulin growth
      factors with gonadotropins. Finally, gonadotropins are widely studied for their
      role in the maintenance of the proper balance between cell proliferation and
      differentiation, and therefore in cancer.

PMID- 27697207
TI  - Brown adipose tissue.

PMID- 27697208
TI  - The rediscovery of BAT in adult humans using imaging.
AB  - Human brown adipose tissue has been acknowledged in newborns and children but in
      adults the first printed publications are from the beginning of 20th century.
      Further evidence of the existence of adult brown fat was published throughout the
      century but only very recently the functionality of active brown adipose tissue
      in vivo in adulthood was confirmed. This was contributed mainly by advanced
      imaging technology, namely hybrid positron emission tomography (PET) and computed
      tomography (CT), being able to combine functional and anatomical imaging data.
      Functionality is most commonly measured with glucose analog, 18F-fluoro-2-deoxy-d
      glucose (FDG) but other tracers for other functions than glucose uptake have been
      introduced as well. Growing body of evidence has increased the knowledge of the
      role of brown adipose tissue in human metabolism and energy expenditure,
      providing a promising option for the management of body weight balance and
      disturbed glucose and lipid metabolism.

PMID- 27697209
TI  - Browning and thermogenic programing of adipose tissue.
AB  - The view of adipose tissue as solely a fat storing organ has changed
      significantly over the past two decades with the discoveries of numerous
      adipocyte-secreted factors, so called adipokines, and their endocrine functions
      throughout the body. The newest chapter added to this story is the finding that
      adipose tissue is also a thermogenic organ contributing to energy expenditure
      through actions of specialized, heat-producing brown or beige adipocytes. In
      contrast to bone fide brown adipocytes, beige cells develop within white fat
      depots in response to various stimuli such as prolonged cold exposure,
      underscoring the great thermogenic plasticity of adipose tissue. The energy
      dissipating properties of beige and/or brown adipocytes hold great promise as a
      novel therapeutic concept against obesity and related complications. Hence,
      identifying the specific thermogenic adipocyte populations in humans and their
      pathways of activation are key milestones of current metabolism research. Here we
      will discuss the recent advances in the understanding of the molecular and
      physiological mechanisms of adipose tissue browning.

PMID- 27697210
TI  - Implications of thermogenic adipose tissues for metabolic health.
AB  - Excess and ectopic fat accumulation in obesity is a major risk factor for
      developing hyperlipidemia, type 2 diabetes and cardiovascular disease. The
      activation of brown and/or beige adipocytes is a promising target for the
      treatment of metabolic disorders as the combustion of excess energy by these
      thermogenic adipocytes may help losing weight and improving plasma parameters
      including triglyceride, cholesterol and glucose levels. The regulation of heat
      production by thermogenic adipose tissues is based on a complex crosstalk between
      the autonomous nervous system, intracellular and secreted factors. This
      multifaceted alignment regulates thermogenic demands to environmental
      circumstances in dependence on available energy resources. This review summarizes
      the current knowledge how thermogenic tissues can be targeted to combat the
      burden of diseases with a special focus on lipid metabolism and diseases related
      to lipoprotein metabolism.

PMID- 27697211
TI  - The role of BAT in cardiometabolic disorders and aging.
AB  - The demonstration of the presence of metabolically active brown adipose tissue
      (BAT) in adult humans using positron emission tomography (PET) over the past
      decade has lead to the rapid development of our knowledge regarding the role of
      BAT in energy metabolism in animal models and in humans. Although animal models
      continue to provide highly valuable information regarding the mechanisms
      regulating BAT development, mass and metabolic functions, these studies led to
      many assumptions that have been at best only partially verified in humans so far.
      Combined to some limitations of the current investigation approaches used in
      humans, this has lead to speculation on the potential role of BAT dysfunction in
      the development of cardiometabolic disorders and on the potential of BAT
      metabolic activation to treat these conditions. Here we propose a critical review
      of the evidence for the implication of BAT in cardiometabolic health.

PMID- 27697212
TI  - Hormonal and nutritional signalling in the control of brown and beige adipose
      tissue activation and recruitment.
AB  - Recent research has revealed that the activity of adipose tissue (BAT) in adult
      humans is higher than previously thought, and that obese patients show abnormally
      low levels of brown fat activity. Studies in experimental animals have shown that
      BAT is a site of energy expenditure, and that BAT activity protects against
      obesity and associated metabolic diseases. The action of the sympathetic nervous
      activity on BAT depots is considered the main regulator of BAT activity in rodent
      models and possibly also in humans. However, recent research has revealed the
      existence of additional hormonal factors, produced by distinct peripheral tissues
      or present in the diet, that influence the amount and activity of BAT. These
      hormonal factors may act on BAT directly, but also indirectly by targeting the
      brain and determining the intensity of sympathetic action upon BAT.
      Identification and characterization of novel factors that control BAT may provide
      clues for the development of new strategies to treat obesity and metabolic
      diseases.

PMID- 27697213
TI  - Estradiol and brown fat.
AB  - Ovarian steroids, such as estradiol (E2), control a vastness of physiological
      processes, such as puberty, reproduction, growth, development and metabolic rate.
      In fact, physiological, pathological, pharmacological or genetically-induced
      estrogen deficiency causes increased appetite and reduced energy expenditure,
      promoting weight gain and ultimately leading to obesity. Remarkably, estrogen
      replacement reverts those effects. Interestingly, although a wealth of evidence
      has shown that E2 can directly modulate peripheral tissues to exert their
      metabolic actions, novel data gathered in recent years have shown that those
      effects are mainly central and occur in the hypothalamus. Here, we will review
      what is known about the actions of E2 on energy homeostasis, with particular
      focus on brown adipose tissue (BAT) thermogenesis.

PMID- 27697214
TI  - Activation and recruitment of brown adipose tissue by cold exposure and food
      ingredients in humans.
AB  - Since the recent re-discovery of brown adipose tissue (BAT) in adult humans, this
      thermogenic tissue has attracted increasing interest. The inverse relationship
      between the BAT activity and body fatness suggests that BAT, because of its
      energy dissipating activity, is protective against body fat accumulation. Cold
      exposure activates and recruits BAT in association with increased energy
      expenditure and decreased body fatness. The stimulatory effects of cold are
      mediated through transient receptor potential channels (TRP), most of which are
      also chemesthetic receptors for various food ingredients. In fact, capsaicin and
      its analog capsinoids, representative agonists of TRPV1, mimic the effects of
      cold to decrease body fatness through the activation and recruitment of BAT. The
      anti-obesity effect of some other food ingredients including tea catechins may
      also be attributable to the activation of the TRP-BAT axis. Thus, BAT is a
      promising target for combating obesity and related metabolic disorders in humans.

PMID- 27697215
TI  - Differential expression of toll-like receptors in the human placenta across early
      gestation.
AB  - Toll-like receptors (TLRs) are an essential component of the innate immune
      system. While a number of studies have described TLR expression in the female
      reproductive tract, few have examined the temporal expression of TLRs within the
      human placenta. We hypothesized that the pattern of TLR expression in the
      placenta changes throughout the first and second trimester, coincident with
      physiological changes in placental function and the demands of innate immunity.
      We collected first and second trimester placental tissue and conducted
      quantitative PCR analysis for TLRs 1-10, followed by immunohistochemistry to
      define the cell specific expression pattern of a subset of these receptors.
      Except for the very earliest time points, RNA expression for TLRs 1-10 was stable
      out to 20 weeks gestation. However, the pattern of protein expression evolved
      over time. Early first trimester placenta demonstrated a strong, uniform pattern
      predominantly in the inner villous cytotrophoblast layer. As the placenta matured
      through the second trimester, both the villous cytotrophoblasts and the pattern
      of TLR expression within them became disorganized and patchy, with putative
      Hofbauer cells now identifiable in the tissue also staining positive. We conclude
      from this data that placental TLR expression changes over the course of
      gestation, with a tight barrier of TLRs forming a wall of defense along the
      cytotrophoblast layer in the early first trimester that breaks down as pregnancy
      progresses. These data are relevant to understanding placental immunity against
      pathogen exposure throughout pregnancy and may aid in our understanding of the
      vulnerable period for fetal exposure to pathogens.

PMID- 27697217
TI  - Placental exosomes and pre-eclampsia: Maternal circulating levels in normal
      pregnancies and, early and late onset pre-eclamptic pregnancies.
AB  - INTRODUCTION AND AIM: Exosomes are a subtype of extracellular vesicle (20-130 nm)
      released by biological cells under normal and pathological conditions. Although
      there have been reports of circulating exosomes in normal pregnancy, the
      relevance of placental-derived exosomes in normal and abnormal pregnancies still
      needs to be elucidated. The aim of this study was to quantify total and placental
      derived exosomes in maternal plasma from normal (N), early onset- and late onset
      preeclampsia (PE). METHOD: Plasma samples were obtained from pregnant women in
      the third trimester, for the isolation of exosomes by differential
      ultracentrifugation. Total exosomes were quantified using nanoparticle tracking
      analysis and immuno-reactive exosomal CD63 quantification. Placental-derived
      exosomes were quantified using placental alkaline phosphatase (PLAP) as a
      specific marker. The contribution of placental-derived exosomes to total exosomes
      in maternal plasma was determined by the ratio of PLAP+ exosomes to CD63+
      exosomes. RESULTS: The concentration of total exosomes significantly increased in
      early onset-PE and late onset-PE compared to N (<=33 weeks) and N (>=34 weeks).
      The relative concentration of placental-derived exosomes significantly increased
      in early onset-PE but decreased in late onset-PE compared to N. The ratio of
      PLAP+ exosomes to total number of exosomes significantly decreased in early onset
      PE and late onset-PE. A positive correlation between total and placental-derived
      exosomes were obtained in N (<=33 weeks: Pearson's r = 0.60, >=34 weeks:
      Pearson's r = 0.67) and early onset-PE (Pearson's r = 0.51, p < 0.05) with the
      inverse in late onset-PE (Pearson's r = -0.62, p < 0.01). CONCLUSION: The
      differences in the contribution of placental-derived exosomes to total exosomes
      in maternal circulation suggests a possible pathophysiological role of placental
      derived exosomes in pre-eclampsia.

PMID- 27697216
TI  - Effect of selective fetectomy on morphology of the mouse placenta.
AB  - INTRODUCTION: Placental examination is recommended when genetic mutations cause
      fetal lethality in mice. But how fetal death alters histomorphology of the
      surviving mouse placenta is not known. METHODS: Placentas were examined at E17.5
      after fetectomy of 1-2 fetal mice per pregnancy at either embryonic day (E) 15.5
      (N = 8; Fx-2 group) or E13.5 (N = 5; Fx-4 group), which left 12 +/- 2 surviving
      fetuses per litter. RESULTS: Fetectomy caused no changes in placental weights and
      no increases in placental hypoxia (pimonidazole staining). The size and cell
      morphology of the decidua and junctional zone regions were unchanged and, in the
      Fx-2 group, these regions became significantly less hypoxic. Significant changes
      in labyrinth volume included a 30% increase in the Fx-2 group and in both groups,
      a >50% decrease in % fetal blood space and >40% increase in % labyrinth tissue.
      Maternal blood sinusoid volume was unchanged. Cell death in the labyrinth was
      significantly increased (22-fold increase in TUNEL staining) whereas placental
      mRNA expression of the proliferation marker Mki67 was unchanged. mRNA expression
      of sFlt1 and Prl3b1 (mPL-II) was unchanged in the labyrinth and junctional zone
      tissues in the Fx-2 group and in whole placental tissue in the Fx-4 group.
      DISCUSSION: Placental examination of the junctional zone and decidual regions
      after spontaneous fetal death in late gestation is likely to yield useful
      phenotypic information and abnormalities that may contribute to fetal death. In
      contrast, labyrinth abnormalities including increased tissue volume and reduced
      fetoplacental vascularity may not be due to genetic perturbation nor predate
      fetal death.

PMID- 27697218
TI  - Vasoactivity of the rat endovascular trophoblast.
AB  - INTRODUCTION: Rat endovascular trophoblasts (EVasT) express smooth muscle (SM)
      proteins and contract ex vivo upon exposure to endothelin-1 (ET1) via receptors A
      and B (ETA, ETB). Presently, we investigated the EVasT response to NOS inhibition
      (N-Nitro-l-arginine methyl ester hydrochloride, l-NAME), and potentiation by NO
      donor [S-Nitroso-N-Acetyl-D,l-Penicillamine (SNAP)] following KCl precontraction.
      M&M: Luminal surface area (LSA) of remodeled spiral artery rings (SAR) devoid of
      SM was measured ex vivo upon exposure to l-NAME alone; l-NAME and ET1
      representing the combined contractile effect of both ET1 receptors; l-NAME with
      ET1 and ETA antagonist, representing the isolated contractile effect via ETB. In
      another experiment we administered SNAP to KCl precontracted SAR. Statistical
      analysis was performed using 2-way mixed ANOVA and repeated measures. RESULTS: l
      NAME reduced LSA by 2.22%, 95% CI [0.83%, 3.60%] compared with control. ET1 and l
      NAME reduced LSA immediately, compared with a plateau at 60min by ET1 alone. The
      isolated ET1 constrictive effect via ETB, reduced LSA by 5.94%; 95% CI [3.47%,
      8.41%], significantly more than that obtained via ETA following 36 min of the
      experiment by 0.88%; 95%CI [0.09%, 1.67%]. Addition of KCl reduced LSA by 11.9%,
      95% CI [9.6%, 14.1%]. Addition of SNAP increased LSA by 3.0%, 95% CI [1.7%,
      4.3%]. CONCLUSIONS: EVasT of the rat remodeled spiral artery react to ET1 and KCl
      similar to vascular SM: contract via both ET1 receptors and KCl and relax by ET1
      via ETB and by SNAP. This phenomenon may play a role in rat models of gestational
      vasoactive systems dysregulation.

PMID- 27697220
TI  - Upregulation of VEGF by small activating RNA and its implications in
      preeclampsia.
AB  - INTRODUCTION: Preeclampsia is a severe pregnancy complication mostly due to
      inadequate vascular dilation and remodeling of spiral arteries. VEGF, the major
      factor for angiogenesis, is necessary for modulating angiogenic processes in the
      placenta. Hence reduction of VEGF in gestational hypertension may also lead to
      hypoperfusion and subsequent hypoxia of the fetus in hypertensive pregnancy.
      METHODS: This study aimed at elucidating the mechanism of action of VEGF in
      preeclampsia. Small activating RNAs (saRNA) were used to upregulate VEGF
      expression in human trophoblast cells (HTR-8/SVneo). The VEGF expression level
      was analyzed by real-time quantitative PCR and western blot, while its
      transfection efficiency was measured by flow cytometer assay. Cell migration was
      analyzed by a wound scratch assay. NO secretion was detected by determining NO
      metabolites. eNOS expression was analyzed by western blot. Tube formation
      function of cells was then analyzed by matrigel migration assay. RESULTS: VEGF
      expression significantly increased after saRNA transfection (all p < 0.05). NO
      secretion and eNOS expression significantly increased by saRNA in HTR-8/SVneo
      cells (p = 0.0003 and 0.032 respectively). The migration ability and tube
      formation function of HTR-8/SVneo cells were enhanced by saRNA (p = 0.024 and
      0.013 respectively). TNF-alpha inhibited VEGF-downstream eNOS-NO pathway activity
      as well as cell migration and tubulogenesis, while enforcing the expression of
      VEGF attenuated all the insults induced by TNF-alpha. CONCLUSIONS: Utilizing an
      RNA activation strategy to increase endogenous VEGF expression could be an
      emerging and effective approach for the treatment of preeclampsia.

PMID- 27697219
TI  - A new biological and clinical resource for research into pregnancy complications:
      The Baby Bio Bank.
AB  - About 20% of pregnancies are affected by some form of complication. Research has
      shown that anomalies in implantation, development, and growth of the fetus;
      ineffective nutrient exchange between mother and fetus due to placental
      dysfunction; and maternal problems such as hypertension or infection during
      pregnancy can all lead to adverse pregnancy outcomes. However, the molecular
      aetiology of such events remains poorly understood. Fetal growth restriction
      (FGR), recurrent miscarriage (RM), preterm birth (PTB), and pre-eclampsia (PE)
      are the most common pregnancy complications encountered in the UK and these
      outcomes can result in an array of morbidities in both mother and baby, and in
      the most severe cases in mortality. We need to know more about normal pregnancy
      and where the important triggers are for failure. This prompted us to collect a
      large set of biological samples with matching clinical data from over 2500 normal
      and abnormal pregnancies, for use in research into these conditions. This paper
      outlines the nature of these sample sets and their availability to academia and
      industry, with the intention that their widespread use in research will make
      significant contributions to the improvement of maternal and fetal health
      worldwide (http://www.ucl.ac.uk/tapb/sample-and-data-collections-at-ucl/biobanks
      ucl/baby-biobank).

PMID- 27697221
TI  - Quality of placental RNA: Effects of explant size and culture duration.
AB  - We evaluated the impact of placental micro (<=50 mg) and macro (~200 mg)
      explants, oxygen concentration and culture method on placental RNA quality after
      long-term culture. Our findings show that micro explants cultured at 8% oxygen
      have the best RNA quality and tissue structure. Macro explants were less viable
      after long-term culture. Macro explants and explants undergoing syncytial
      degeneration produced poor quality RNA and should be avoided.

PMID- 27697223
TI  - Compartmentalized localization of 11beta-HSD 1 and 2 at the feto-maternal
      interface in the first trimester of human pregnancy.
AB  - Glucocorticoids are engaged in a number of actions at the feto-maternal interface
      for the establishment of early pregnancy. However, excessive glucocorticoids can
      be deleterious to fetal development. Therefore, compartmentalized distribution of
      11beta-hydroxysteroid dehydrogenase 1 and 2 (11beta-HSD1 and 2), which
      regenerates and inactivates cortisol respectively, would ensure an optimal
      cortisol concentration at the feto-maternal interface for the establishment of
      early gestation. However, the distribution pattern of 11beta-HSD1 and 2 at the
      feto-maternal interface in early human pregnancy is not clearly defined. Here we
      showed that 11beta-HSD1 distributed extensively on the maternal side including
      decidual stromal cells and epithelial cells but scarcely on the fetal side except
      for localization in the fetal blood vessels of the chorionic villi. In contrast,
      11beta-HSD2 was abundantly localized in syncytial layer of the chorionic villi
      and the decidual epithelium. In primary cultures, cortisol upregulated not only
      11beta-HSD1 expression in decidual stromal cells but also 11beta-HSD2 expression
      in villous trophoblasts of early pregnancy. Further studies revealed that
      cortisol inhibited the expression of interleukin-1beta and 6 in decidual stromal
      cells and villous trophoblasts, and stimulated expression of human chorionic
      gonadotropin in villous trophoblasts. Collectively, this study has revealed a
      compartmentalized distribution pattern of 11beta-HSD 1 and 2 at the feto-maternal
      interface, both of which can be upregulated by glucocorticoids, suggesting that a
      coordinated interaction between 11beta-HSD 1 and 2 may exist to ensure an optimal
      cortisol concentration at discrete locations at the feto-maternal interface for
      the establishment of early pregnancy.

PMID- 27697222
TI  - Modulation of FABP4 hypomethylation by DNMT1 and its inverse interaction with miR
      148a/152 in the placenta of preeclamptic rats and HTR-8 cells.
AB  - Inflammation and dysregulated lipid metabolism are involved in the pathogenesis
      of preeclampsia, and fatty acid binding protein 4 (FABP4) is known to regulate
      both inflammation and lipid metabolism. In the present study, we elucidated the
      role of FABP4 using in vitro and in vivo models of preclampsia. We found
      increased expression of FABP4 in the placenta of preeclamptic rats, which was
      further confirmed in HTR-8 cells, an extravillous trophoblast cell line, treated
      with L-NAME. Overexpression of FABP4 in HTR-8 cells resulted in upregulated
      expression of pro-inflammatory cytokines IL-6 and TNF-alpha, and increased lipid
      accumulation, suggesting that FABP4 plays a role in preeclampsia. Furthermore,
      downregulation of methylation in the promotor resulted in increased FABP4
      expression, which was mediated by downregulated DNA methyltransferase 1 (DNMT1).
      Bioinformatics analysis showed that miR-148a/152 regulated the expression of
      DNMT1, and additional in vitro studies revealed that miR-148a/152 inhibited DNMT1
      expression by directly binding to its 3'-UTR. Interestingly, DNMT1 enhanced the
      expression of miR-148a/152 by downregulation of methylation in its promotor.
      Taken together, our results showed that FABP4 may be involved in the pathogenesis
      of preeclampsia, and the expression of FABP4 is enhanced by miR-148a/152 mediated
      inhibition of DNMT1 expression.

PMID- 27697224
TI  - Placental histological examination and the relationship with oxidative stress in
      preterm infants.
AB  - BACKGROUND: Prenatal conditions of enhanced oxidative stress (OS) linked to
      inflammation or hypoxia have been associated with impaired fetal growth and
      preterm delivery. Little is known regarding biomarkers of OS in the cord blood of
      preterm infants and placental histological patterns. OBJECTIVES: To test the
      hypothesis that placental lesions indicating chorioamnionitis (CA) or vascular
      underperfusion (VU) are associated with increased OS in the offspring. METHODS:
      120 neonates born below 29+6 weeks of gestational age (GA) were enrolled.
      Histological characteristics of placentas from their mothers were classified as
      normal (CTRL group), histological CA (HCA) and vascular underperfusion (VU).
      Serum concentrations of isoprostanes (IsoPs), non-protein bound iron (NPBI) and
      advanced oxidative protein products (AOPP), were determined in cord blood.
      RESULTS: IsoPs, NPBI and AOPP were significantly increased in HCA group compared
      to CTRL group. The multivariable regression model, adjusted for GA, maternal age,
      parity, maternal diabetes, maternal obesity and presence/absence of fetal growth
      restriction (FGR), showed a significant association between the presence of HCA
      and increased OS biomarkers levels in cord blood (IsoPs: p = 0.006; NPBI: p =
      0.014; AOPP: p = 0.007). Placental VU lesions were significantly associated with
      higher umbilical IsoPs, NPBI and AOPP levels (IsoPs: p = 0.008; NPBI: p = 0.002;
      AOPP: p = 0.040). In the cases of placental VU lesions associations were also
      found between high AOPP levels and low GA (p = 0.002) and the presence of fetal
      growth restriction (p = 0.014). CONCLUSIONS: Placental lesions indicating
      inflammation or impaired perfusion are associated with higher cord blood levels
      of OS biomarkers explaining the fetal susceptibility to oxidative injury and the
      need of antioxidant protection.

PMID- 27697225
TI  - Placental vascularity and markers of angiogenesis in relation to prenatal growth
      status in overnourished adolescent ewes.
AB  - INTRODUCTION: Placental vascularity may be important in the development of fetal
      growth restriction (FGR). The overnourished adolescent ewe is a robust model of
      the condition, with ~50% of offspring demonstrating FGR (birthweight >2 standard
      deviations below optimally-fed control mean). We studied whether placental
      vascularity, angiogenesis and glucose transport reflect FGR severity. METHODS:
      Singleton pregnancies were established in adolescent ewes either overnourished to
      putatively restrict fetoplacental growth (n = 27) or control-fed (n = 12). At
      131d (term = 145d) pregnancies were interrupted and fetuses classified as FGR (n
      = 17, <4222 g, -2SD below control-fed mean) or non-FGR (n = 10). Placentome
      capillary area density (CAD), number density (CND), surface density (CSD), and
      area per capillary (APC) in the fetal cotyledon (COT) and maternal caruncle (CAR)
      were analysed using immunostaining. COT/CAR mRNA expression of angiogenic
      ligands/receptors and glucose transporters were measured by qRT-PCR. RESULTS:
      Fetal weight was reduced in FGR vs. Non-FGR/Control groups. Total placentome
      weight was Control > Non-FGR > FGR and fetal:placental weight ratios were higher
      in overnourished versus Control groups. COT vascular indices were Non-FGR > FGR >
      Control. COT-CAD, CSD and APC were significantly greater in Non-FGR overnourished
      versus Control and intermediate in FGR groups. CAR vascularity did not differ.
      CAR-VEGFA/FLT1/KDR/ANGPT1/ANGPT2/SLC2A1/SLC2A3 mRNA was lower and COT-ANGPT2
      higher in overnourished versus Control groups. DISCUSSION: Relative to control
      intake pregnancy, overnourished pregnancies are characterised by higher COT
      vascularity, potentially a compensatory response to reduced nutrient supply,
      reflected by higher fetal:placental weight ratios. Compared with overnourished
      pregnancies where fetal growth is relatively preserved, overnourished pregnancies
      culminating in marked FGR have less placental vascularity, suggesting incomplete
      adaptation to the prenatal insult.

PMID- 27697226
TI  - Alcohol exposure impairs trophoblast survival and alters subtype-specific gene
      expression in vitro.
AB  - Maternal alcohol consumption is common prior to pregnancy recognition and in the
      rat results in altered placental development and fetal growth restriction. To
      assess the effect of ethanol (EtOH) exposure on the differentiation of
      trophoblast stem (TS) cells, mouse TS lines were differentiated in vitro for 6
      days in 0%, 0.2% or 1% EtOH. This reduced both trophoblast survival and
      expression of labyrinth and junctional zone trophoblast subtype-specific genes.
      This suggests that fetal growth restriction and altered placental development
      associated with maternal alcohol consumption in the periconceptional period could
      be mediated in part by direct effects on trophoblast development.

PMID- 27697227
TI  - DNA methylation-associated repression of MEST/PEG1 expression contributes to the
      invasion of extravillous trophoblast cells.
AB  - INTRODUCTION: The invasion of extravillous cytotrophoblasts (EVTs) into the
      maternal uterine decidua and vasculature is critical for human placenta
      development and pregnancy maintenance. The imprinted gene MEST/PEG1 has been
      implicated in trophoblast development; however, the role of MEST in EVT invasion
      and the accompanying early pregnancy complications are not fully understood.
      METHODS: Western blot, immunofluorescence and immunohistochemistry were used to
      detect MEST protein expression and localization by using antibodies recognize 2
      reported isoforms. Specific small interference RNA (siRNA) targeting both of the
      MEST isoforms was applied to silence MEST expression in extravillous explants and
      HTR8/SVneo cells. Cell invasion and migration were assessed using the Matrigel
      invasion, Transwell migration assay and the xCELLigence system. Promoter DNA
      methylation was examined using bisulfite-sequencing polymerase chain reaction
      (BSP). RESULTS: MEST protein was highly expressed in EVTs in the first trimester
      placenta and in the invasive EVT cell lines HTR-8/Svneo and HPT-8. Weak MEST
      expression was found in cytotrophoblasts (CTBs) and the choriocarcinoma-derived
      CTB cell line JEG-3. The specific siRNA knockdown of MEST expression
      significantly reduced HTR-8/Svneo cell invasion and migration as well as
      extravillous explant outgrowth, which were associated with the downregulation of
      Twist, N-cadherin and Vimentin. Decreased MEST protein expression with isoform 2
      promoter hypermethylation was observed in the placentas of missed abortions,
      suggesting a possible pathological mechanism of missed abortion. CONCLUSIONS:
      Suppressed expression of MEST was associated with its isoform 2 promoter
      hypermethylation ex vivo placenta tissues and in vitro cultured EVT cell lines.
      The present results provide a possible pathological mechanism of missed abortion.

PMID- 27697229
TI  - Hospital information system institutionalization processes in indonesian public,
      government-owned and privately owned hospitals.
AB  - The Hospital Information System (HIS) could help hospitals as a public entity to
      provide optimal health services. One of the main challenges of HIS implementation
      is an institutional change. Using institutional theory as the analytical lens,
      this study aims to explain the institutionalization of HIS as an instance of e
      health initiatives in Indonesia. Furthermore, this paper aims for hospital
      management and researchers to improve the understanding of the social forces that
      influence hospital personnel's HIS acceptance within an organizational context.
      We use case studies from four public, government-owned hospitals and four
      privately owned (public and specialty) hospitals to explain the HIS
      institutionalization process by exploring the three concepts of institutional
      theory: institutional isomorphism, institutional logic, and institutional
      entrepreneurship. This study reveals that differences exist between public,
      government-owned and private hospitals with regard to the institutionalization
      process: public, government-owned hospitals' management is more motivated to
      implement HIS to comply with the regulations, while private hospitals' management
      views HIS as an urgent requirement that must be achieved. The study findings also
      reveal that various institutional isomorphism mechanisms and forms of
      institutional logic emerge during the process. Finally, three factors-self
      efficacy, social influence, and management support-have a significant influence
      on the individual acceptance of HIS.

PMID- 27697228
TI  - Capturing the patients' voices: Planning for patient-centered electronic health
      record use.
AB  - OBJECTIVES: To understand (1) the perceptions of patients regarding use of EHR
      during clinic visits, (2) the impact of the presence of EHR on patient
      interactions with physicians, and (3) the ways in which EHR usage might increase
      patient engagement. METHODS: We conducted semi-structured interviews of a
      convenience sample of patients of internal medicine resident doctors from three
      primary care clinics. Interviews were audio-recorded and transcribed verbatim. We
      used thematic analysis to identify themes from the transcripts. Informed consent
      was obtained from each participant. RESULTS: We interviewed 32 patients; 37.5%
      male. Our analysis revealed three primary themes: (1) the views and beliefs of
      patients on the use of EHR in clinics, (2) patients' perception of the
      communication skills of residents, and (3) patients' perceptions about
      information sharing, patient engagement, and health education related to the EHR.
      An invitation to patients to view the screen as the physician interprets its
      content increases patient satisfaction and understanding. Residents' possessed
      skills in communication is not impeded when using EHR. CONCLUSION: Patients
      generally express a positive or neutral perception of EHR use during clinic
      visits. Using information voiced by patients, we can teach health providers EHR
      strategies that are likely to engage patients in the visit and engender their
      trust.

PMID- 27697230
TI  - Inpatient satisfaction and usage patterns of personalized smart bedside station
      system for patient-centered service at a tertiary university hospital.
AB  - OBJECTIVE: Bedside stations, also known as bedside terminals, are in place to
      enhance the quality and experience of a hospital's healthcare service delivery.
      The purpose of this study was to identify information needs and overall
      satisfaction with the personalized patient bedside system, called Smart Bedside
      Station (SBS) system, embedded in a tertiary general university hospital.
      METHODS: End-user responses on the satisfaction survey and system usage logs of
      the SBS system were collected and analyzed. For the user opinion survey, 156
      nurses and 1914 patients, their family members, or caregivers participated during
      the evaluation period of 2013 to 2014 in this study. All working nurses in the
      SBS-installed ward were answered the paper-based evaluation, for complete
      enumeration survey. Inpatients were voluntary participated to deliver the online
      questionnaire on the SBS menu. We also explored system log data including page
      calls and usage time from December 2013 to 2015. RESULTS: Regarding the
      relationship of overall satisfaction of the SBS with patient's characteristics,
      patient's education status and degree of familiarity with the smart device were
      statistically significant. From the analysis of system logs, Personalized My
      Menu(28.0%) was the most frequently used menu item (except for TV and Internet
      entertainment service use of 62.7%),it provides individual health information,
      such as laboratory test results, hospital fee check, message logs, daily
      medication information, and meal information. Next frequently used menus were
      information support(4.9%) which deliver hospital guide and health information and
      convenience service ordering(4.4%) such as meal order, bed sheet change.
      Satisfaction survey results and log data results show that the personalized
      service enhances the user satisfaction during hospital admission. CONCLUSIONS:
      Our post-implementation experience and subsequent assessment of SBS system is
      capable of providing insights into improving the hospital information system and
      service contents for patient-centered services. Further research should be
      directed at developing sophisticated patient-centered services as a communication
      tool between the hospital and the patient.

PMID- 27697231
TI  - MiBAlert-a new information tool to fight multidrug-resistant bacteria in the
      hospital setting.
AB  - BACKGROUND: Although the timely isolation of patients is an essential
      intervention to limit spread of drug-resistant bacteria, information about the
      colonization status is often unavailable or lost when patients are readmitted or
      transferred between hospitals. Therefore, carriers of drug resistant bacteria are
      not recognized sufficiently early, and proper and timely isolation precautions
      are not taken. Consequently, resistant bacteria of public health concerns
      including vancomycin resistant enterococci (VRE) and methicillin resistant
      Staphylococcus aureus (MRSA) can spread epidemically. To ensure timely
      identification and proper isolation of such patients we developed an automatic
      real-time alert of carriers of drug resistant bacteria. OBJECTIVES: The aim of
      this paper is to describe the system, called MiBAlert, and share the initial
      experiences in connection with an outbreak of VRE in the greater Copenhagen area
      (the Capital region), Denmark. METHODS: We obtained data on cases of VRE from
      hospitals in Copenhagen during the period when the first version of MiBAlert was
      implemented and log-data on the use of MiBAlert. Furthermore, a survey was
      conducted among 88 staff members to investigate their experiences of MiBAlert.
      RESULTS: The alert is a tool directed toward healthcare personnel accessing the
      electronic health record (EHR) and those further involved in the care and
      treatment of the patient. It is based on a web service using data from the
      national microbiological database, MiBa. MiBAlert is a real-time electronic non
      intrusive alert generated automatically in the header of the EHR each time record
      is accessed. On February 15, 2015 a pilot version of MiBAlert was launched. All
      positive tests for VRE throughout 1year were shown with alert status by MiBAlert
      visible to all medical staff with access to EHR. The alert system was
      automatically updated directly in the EHR across the five hospitals in the
      Capital region. We found that the system performed satisfactorily, being
      operational 24/7 all 135 trial days, apart from 72min, for all the hospitals. Of
      the staff who responded to the survey, 82% considered that MiBAlert overall
      improved compliance with isolation precautions regarding VRE-positive patients.
      We found a marked decline of new patients infected or colonized with VRE
      concomitant with the implementation of MiBAlert and the survey results.
      CONCLUSION: We found that MiBAlert was a valuable tool in a bundle approach to
      counter a multiple hospital outbreak of VRE, and that it has a great potential to
      improve the control of other drug-resistant bacteria.

PMID- 27697232
TI  - The development and use of a new methodology to reconstruct courses of admission
      and ambulatory care based on the Danish National Patient Registry.
AB  - INTRODUCTION: The Danish National Patient Registry (DNPR) contains clinical and
      administrative data on all patients treated in Danish hospitals. The data model
      used for reporting is based on standardized coding of contacts rather than
      courses of admissions and ambulatory care. METHODS: To reconstruct a coherent
      picture of courses of admission and ambulatory care, we designed an algorithm
      with 28 rules that manages transfers between departments, between hospitals and
      inconsistencies in the data, e.g., missing time stamps, overlaps and gaps. We
      used data from patients admitted between 1 January 2010 and 31 December 2014.
      RESULTS: After application of the DNPR algorithm, we estimated an average of
      1,149,616 courses of admission per year or 205 hospitalizations per 1000
      inhabitants per year. The median length of stay decreased from 1.58days in 2010
      to 1.29days in 2014. The number of transfers between departments within a
      hospital increased from 111,576 to 176,134 while the number of transfers between
      hospitals decreased from 68,522 to 61,203. CONCLUSIONS: We standardized a 28-rule
      algorithm to relate registrations in the DNPR to each other in a coherent way.
      With the algorithm, we estimated 1.15 million courses of admissions per year,
      which probably reflects a more accurate estimate than the estimates that have
      been published previously. Courses of admission became shorter between 2010 and
      2014 and outpatient contacts longer. These figures are compatible with a cost
      conscious secondary healthcare system undertaking specialized treatment within a
      hospital and limiting referral to advanced services at other hospitals.

PMID- 27697234
TI  - Sociotechnical analysis of nurses' use of personal mobile phones at work.
AB  - BACKGROUND: Nurses' use of personal mobiles phones at work is a growing trend in
      healthcare organizations. Although recent studies have explored the positive and
      negative implications of nurses using personal mobile phones at work, none has
      yet analyzed the interactions of sociotechnical components (users, technology and
      policy) on nurses' use of personal mobile phones at work. OBJECTIVES: Identify
      sociotechnical interactions by analyzing each sociotechnical component (users,
      technology and policy) that affects nurses' use of personal mobile phones at
      work. METHODS: In-depth interviews were conducted with 30 nurses employed in 13
      hospitals in the Philippines. The respondents include staff nurses (n=23), charge
      nurses (n=4), and nurse managers (n=3). Staff nurses were asked on their use of
      personal mobile phones at work, while charge and nurse managers were asked on
      their observations regarding staff nurses' use of personal mobile phones at work.
      Responses were analyzed qualitatively using sociotechnical analysis. RESULTS:
      Sociotechnical analysis indicated that staff nurses used their personal mobile
      phones at work in various ways because its use helped in their nursing work, but
      inevitably altered a few of their routines. Although most hospitals had policies
      that prohibit the use of mobile phones, staff nurses justified their use of
      personal mobile phones by using it for work purposes and for the benefit of their
      patients. Staff nurses highlighted the absence of hospital-provided mobile phones
      as a key reason for using personal mobile phones at work. Charge nurses and nurse
      managers also influenced staff nurses' use of personal mobile phones at work.
      CONCLUSIONS: Nurses could use their personal mobile phones at work for work
      purposes to enhance their clinical performance and improve patient care. Hospital
      administrators can leverage on nurses' use of personal mobile phones at work by
      formulating policies that consider both the benefits and potential drawbacks of
      mobile phone usage. Recommendations are made for the formulation of hospital
      policies to optimize the use of personal mobile phones of nurses at work.

PMID- 27697233
TI  - Assessing the quality of routine data for the prevention of mother-to-child
      transmission of HIV: An analytical observational study in two health districts
      with high HIV prevalence in South Africa.
AB  - BACKGROUND: The prevention of mother-to-child transmission of HIV (PMTCT) is a
      key maternal and child-health intervention in the context of the HIV/AIDS
      pandemic in South Africa. Accordingly, the PMTCT programmes have been
      incorporated in the routine District Health Management Information System (DHMIS)
      which collects monthly facility-based data to support the management of public
      health services. To date, there has been no comprehensive evaluation of the PMTCT
      information system. OBJECTIVES: This study seeks to evaluate the quality of
      output indicators for monitoring PMTCT interventions in two health districts with
      high HIV prevalence. METHODS: An analytical observational study was undertaken
      based on the Performance of Routine Information System Management (PRISM)
      framework and tools, including an assessment of the routine PMTCT data for
      quality in terms of accuracy and completeness. Data were collected from 57 public
      health facilities for six pre-defined PMTCT data elements by comparing the source
      registers with the routine monthly report (RMR), and the RMR with the DMHIS for
      January and April 2012. This was supplemented by the analysis of the monthly data
      reported routinely in the DMHIS for the period 2009-2012. Descriptive statistics,
      analysis of variance (ANOVA) and Bland Altman analysis were conducted using
      STATA(r) Version 13. RESULTS: Although completeness was relatively high at 91%
      (95% CI: 78-100%) at facility level and 96% (95% CI: 92-100%) at district level,
      the study revealed considerable data quality concerns for the PMTCT information
      with an average accuracy between the register and RMR of 51% (95% CI: 44-58%) and
      between the RMR and DHMIS database of 84% (95% CI: 78-91%). We observed
      differences in the data accuracy by organisational authority. The poor quality of
      the data was attributed partly to insufficient competencies of health information
      personnel. CONCLUSIONS: The study suggests that the primary point of departure
      for accurate data transfer is during the collation process. Institutional
      capacity to improve data quality at the facility level and ensure core
      competencies for routine health information system (RHIS)-related tasks are
      needed. Further exploration of the possible factors that may influence data
      accuracy, such as supervision, RHIS processes, training and leadership are
      needed. In particular understanding is needed about how individual actions can
      bring about changes in institutional routines.

PMID- 27697235
TI  - Information needs of Botswana health care workers and perceptions of wikipedia.
AB  - BACKGROUND: Since the UN Human Rights Council's recognition on the subject in
      2011, the right to access the Internet and information is now considered one of
      the most basic human rights of global citizens [1,2]. Despite this, an
      information gap between developed and resource-limited countries remains, and
      there is scant research on actual information needs of workers themselves. The
      Republic of Botswana represents a fertile ground to address existing gaps in
      research, policy, and practice, due to its demonstrated gap in access to
      information and specialists among rural health care workers (HCWs), burgeoning
      mHealth capacity, and a timely offer from Orange Telecommunications to access
      Wikipedia for free on mobile platforms for Botswana subscribers. OBJECTIVES: In
      this study, we sought to identify clinical information needs of HCWs of Botswana
      and their perception of Wikipedia as a clinical tool. METHODS: Twenty-eight
      facilitated focus groups, consisting of 113 HCWs of various cadres based at
      district hospitals, clinics, and health posts around Botswana, were employed.
      Transcription and thematic analysis were performed for those groups. RESULTS:
      Access to the Internet is limited at most facilities. Most HCWs placed high
      importance upon using Botswana Ministry of Health (MoH) resources for obtaining
      credible clinical information. However, the clinical applicability of these
      materials was limited due to discrepancies amongst sources, potentially outdated
      information, and poor optimization for time-sensitive circumstances. As a result,
      HCWs faced challenges, such as loss of patient trust and compromises in patient
      care. Potential solutions posed by HCWs to address these issues included:
      multifaceted improvements in Internet infrastructure, access to up-to-date
      information, transfer of knowledge from MoH to HCW, and improving content and
      applicability of currently available information. Topics of clinical information
      needs were broad and encompassed: HIV, TB (Tuberculosis), OB/GYN (Obstetrics and
      Gynecology), and Pediatrics. HCW attitudes towards Wikipedia were variable; some
      trusted Wikipedia as a reliable point of care information resource whereas others
      thought that its use should be restricted and monitored by the MoH. CONCLUSIONS:
      There is a demonstrated need for accessible, reliable, and up-to-date information
      to aid clinical practice in Botswana. Attitudes towards Wikipedia as an open
      information resource tool are at best, split. Therefore, future studies are
      necessary to determine the accuracy, currency, and relevancy of Wikipedia
      articles on the health topics identified by health care workers as areas of
      information need. More broadly speaking, future efforts should be dedicated to
      configure a quality-controlled, readily accessible mobile platform based clinical
      information application tool fitting for Botswana.

PMID- 27697236
TI  - Introduction.

PMID- 27697237
TI  - Determination of death: Metaphysical and biomedical discourse.
AB  - The prominence of biomedical criteria relying on brain death reduces the impact
      of metaphysical, anthropological, psychosocial, cultural, religious, and legal
      aspects disclosing the real value and essence of human life. The aim of this
      literature review is to discuss metaphysical and biomedical approaches toward
      death and their complimentary relationship in the determination of death. A
      critical appraisal of theoretical and scientific evidence and legal documents
      supported analytical discourse. In the metaphysical discourse of death, two main
      questions about what human death is and how to determine the fact of death
      clearly separate the ontological and epistemological aspects of death. During the
      20th century, various understandings of human death distinguished two different
      approaches toward the human: the human is a subject of activities or a subject of
      the human being. Extinction of the difference between the entities and the being,
      emphasized as rational-logical instrumentation, is not sufficient to understand
      death thoroughly. Biological criteria of death are associated with biological
      features and irreversible loss of certain cognitive capabilities. Debating on the
      question "Does a brain death mean death of a human being?" two approaches are
      considering: the body-centrist and the mind-centrist. By bridging those two
      alternatives human death appears not only as biomedical, but also as metaphysical
      phenomenon. It was summarized that a predominance of clinical criteria for
      determination of death in practice leads to medicalization of death and limits
      the holistic perspective toward individual's death. Therefore, the balance of
      metaphysical and biomedical approaches toward death and its determination would
      decrease the medicalization of the concept of death.

PMID- 27697238
TI  - The acute effects of passive heat exposure on arterial stiffness, oxidative
      stress, and inflammation.
AB  - BACKGROUND AND OBJECTIVE: The aim of the study was to determine the acute effect
      of passive heat exposure (PHE) on arterial stiffness, oxidative stress (OxS) and
      inflammatory parameters. MATERIALS AND METHODS: Subjects were studied in
      thermoneutral conditions before and after PHE in a climatic chamber. Pulse wave
      analysis was used for assessment of central hemodynamic and arterial stiffness
      parameters. Venous blood samples were obtained to measure OxS and inflammatory
      parameters. RESULTS: Rectal temperature increased after PHE exposure compared to
      baseline: 37.01 degrees C+/-0.19 degrees C and 36.4 degrees C+/-0.31 degrees C,
      respectively (P<0.001). There was a 17% (P<0.05) decrease in large artery
      elasticity index (from 24.68+/-5.53 to 20.42+/-2.65mL/mmHg*10), which was
      predicted upon normothermic value (r=-0.878, P<0.01). However, no significant
      changes were found in others arterial stiffness parameters. A 30% (P<0.05)
      increase occurred in blood IL-6 concentration (from 0.43+/-0.15 to 0.56+/
      0.23pg/mL), but OxS parameters remained significantly unchanged. CONCLUSIONS:
      This study describes for the first time acute PHE effects on arterial stiffness,
      inflammation and OxS. PHE significantly decreases large artery elasticity index
      and increases inflammatory IL-6 level. However, further larger investigations are
      needed for clarifying acute PHE effects on arterial function and biomarkers.

PMID- 27697240
TI  - Toxic anterior segment syndrome: Role of enzymatic detergents used in the
      cleaning of intraocular surgical instruments.

PMID- 27697239
TI  - Health care professionals' skills regarding patient safety.
AB  - BACKGROUND AND OBJECTIVE: The importance of patient safety is growing worldwide,
      and every day, health care professionals face various challenges in how to
      provide safe care for their patients. Patient safety skills are one of the main
      tools to ensure safe practice. This study looks to describe health care
      professionals' skills regarding patient safety. MATERIALS AND METHODS: Data were
      collected using the skill scale of the Patient Safety Attitudes, Skills and
      Knowledge (PS-ASK) instrument from different health care professionals (n=1082:
      physicians, head nurses, nurses and nurse assistants) working in hospitals for
      adult patients in three regional multi-profile hospitals in the western part of
      Lithuania. RESULTS: Overall, the results of this study show that based on their
      own evaluations, health care professionals were competent regarding their safety
      skills. In particular, they were competent in the sub-scale areas of error
      analysis (mean=3.09) and in avoiding threats to patient safety (mean=3.31), but
      only somewhat competent in using decision support technology (mean=2.00).
      Demographic and other work related background factors were only slightly
      associated with these patient safety skills areas. Especially, it was noted that
      nurse assistants may need more support from managers and colleagues in developing
      their patient safety skills competence. CONCLUSIONS: This study has served to
      investigate the general skills of health care professionals in regard to patient
      safety. It provides new knowledge about the topic in the context of the Baltic
      countries and can thus be used in the future development of health care services.

PMID- 27697241
TI  - White ring sign for uneventful lenticule separation in small-incision lenticule
      extraction.
AB  - : We describe the white ring sign, which differentiates the posterior and
      anterior lenticular planes in small-incision lenticule extraction. The sign
      identifies the plane of dissection by the anteroposterior relationship between
      the dissecting instrument and the circular white light reflected from the
      lenticular side cut. Differentiating the planes enables the surgeon to dissect
      the anterior plane before the posterior plane, which facilitates smooth lenticule
      extraction and prevents complications such as cap tears, partial lenticule
      dissection, and a torn lenticule. FINANCIAL DISCLOSURE: None of the authors has a
      financial or proprietary interest in any material or method mentioned.

PMID- 27697242
TI  - Treating capsule contraction syndrome with a femtosecond laser.
AB  - : We describe a technique that uses a femtosecond laser (femtosecond laser
      pseudophakic capsulotomy) to treat capsule contraction syndrome (capsule
      phimosis) that may occur after cataract surgery and intraocular lens (IOL)
      implantation. Enlarging the capsulotomy with a femtosecond laser may offer
      advantages over the existing treatment methods, neodymium:YAG laser capsulotomy
      and manual extension of the capsulorhexis. FINANCIAL DISCLOSURE: None of the
      authors has a financial or proprietary interest in any material or method
      mentioned.

PMID- 27697243
TI  - Intraocular lens exchange surgery at a tertiary referral center: Indications,
      complications, and visual outcomes.
AB  - PURPOSE: To identify indications for and visual outcomes of intraocular lens
      (IOL) exchange to understand recent changes in this surgery. SETTING: Academic
      tertiary referral center. DESIGN: Retrospective case series. METHODS: Cases were
      identified by searching the institution's electronic medical records from January
      2010 to September 2015 for patients treated by 1 staff physician with the
      American Medical Association's Current Procedural Terminology code for IOL
      exchange. These cases were reviewed to determine the surgical indication, type of
      IOL removed, type of IOL implanted, time between surgeries, surgical
      complications, and visual outcomes. RESULTS: The study comprised medical records
      of 109 eyes. The mean time between the primary cataract surgery and IOL exchange
      was 1657 days. Dislocation of an in-the-bag posterior chamber IOL (27.5%),
      intolerance of a multifocal IOL (18.3%), and uveitis-glaucoma-hyphema syndrome
      (11.9%) were the most frequent indications for IOL exchange. The final IOL
      position after exchange was most frequently in the capsular bag (43.1%), anterior
      chamber (25.7%), or sulcus (22%). The final visual acuity at 1 month was 20/40 or
      better in 78.9% of cases. Of those not achieving this level of acuity, pathology
      not related to exchange surgery was identified in 48% of cases. The most frequent
      complications after IOL exchange surgery were posterior capsule opacification
      (13.8%), cystoid macular edema (10.1%), and high astigmatism (>1.5 diopters)
      (8.3%). CONCLUSIONS: The most frequent indication for IOL exchange surgery was
      dislocated IOLs; the second most frequent indication was patient dissatisfaction
      after multifocal IOL implantation. The increased ability to place an
      intracapsular IOL with few intraoperative complications and largely treatable
      postoperative complications enhances the effectiveness of IOL exchange surgery
      and patient satisfaction. FINANCIAL DISCLOSURE: Neither author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 27697244
TI  - Clinical outcomes of a new extended range of vision intraocular lens:
      International Multicenter Concerto Study.
AB  - PURPOSE: To analyze the clinical outcomes after implantation of an extended range
      of vision intraocular lens (IOL), the Tecnis Symfony, in a routine clinical
      setting. SETTING: Forty clinical sites in Finland, France, Germany, Norway,
      Spain, Sweden, and the United Kingdom. DESIGN: Prospective case series. METHODS:
      The study comprised 411 patients who had bilateral implantation of the extended
      range of vision IOL, with intended micro-monovision in 1 group (monovision group)
      and intended emmetropia in the other group (non-monovision group). Visual acuity,
      spectacle independence, patient and surgeon satisfaction, and photic phenomena
      were analyzed during the 4- to 6-month follow-up. RESULTS: The monovision group
      comprised 112 patients and the non-monovision group, 299 patients. The mean
      decimal uncorrected distance (UDVA), intermediate (UIVA), and near (UNVA) visual
      acuities were 0.95, 0.81, and 0.69, respectively, 4 to 6 months postoperatively.
      Significantly better UIVA (P = .003) and UNVA (P = .011) were found in the
      monovision group than in the non-monovision group. Spectacle independence was
      high, with 14.4% of eyes requiring reading spectacles frequently. More than 90%
      of patients reported no or mild halos, glare, starbursts, or other photic
      phenomena. Patient satisfaction scores (median) for distance, intermediate, and
      near vision were 9.0, 10.0, and 8.0, respectively. The satisfaction score for
      near vision increased to 9.0 in the monovision group. More than 91% of patients
      said they would recommend the same procedure to their friends and family.
      CONCLUSION: The extended range of vision IOL provided successful visual
      restoration across all distances after cataract surgery, with a minimal level of
      disturbing photic phenomena and high levels of patient satisfaction. FINANCIAL
      DISCLOSURE: Dr. Cochener is a clinical investigator for Revision Optics, Inc.,
      Horus Vision LLC, Alcon Laboratories, Inc., Abbott Medical Optics, Inc., Thea
      Pharma GmbH, and Santen, Inc.; she is also a consultant to Alcon Laboratories,
      Inc., Abbott Medical Optics, Inc., Thea Pharma GmbH, and Santen, Inc.

PMID- 27697245
TI  - Differences in visual quality with orientation of a rotationally asymmetric
      bifocal intraocular lens design.
AB  - PURPOSE: To evaluate visual and perceptual performance for different orientations
      of a rotationally asymmetric bifocal intraocular lens (IOL) (M-Plus) simulated
      optically using a simultaneous vision simulator. SETTING: Instituto de Optica,
      Madrid, Spain. DESIGN: Prospective observational study. METHODS: Perceptual
      quality and decimal high-contrast visual acuity (HCVA) was measured under
      cycloplegia for 8 orientations of the asymmetric bifocal IOL phase pattern at
      far, intermediate, and near distances simulated with a simultaneous vision
      simulator using face images and tumbling E targets. The preferred orientation at
      each distance was calculated as the centroid of the data for 8 orientations. The
      visual Strehl value was calculated using the subjects' ocular aberrations and
      multifocal pattern at each orientation. Optical predictions were obtained by
      implementing a differential visual Strehl values-based ideal observer model.
      RESULTS: The study comprised 20 subjects (aged 21 to 62 years). Horizontal
      orientation (near segment at 0 or 180 degrees +/- 45 [SD]) was preferred by 14
      subjects and by 13 subjects at far and near distances, respectively; 8 subjects
      showed strong orientation preferences. The mean difference in preferred
      orientation between far and near was 27 +/- 22 degrees. No significant
      differences in HCVA were observed. Optical predictions correlated strongly and
      significantly with measurements (far r = 0.71, near r = 0.62; P < .0001). The
      mean difference between measurement and simulation in the preferred orientation
      was 28 +/- 29 degrees at far and 36 +/- 28 degrees at near. CONCLUSIONS: The
      perception varied for different orientations of an asymmetric bifocal IOL design
      tested using a simultaneous vision simulator. Optimum orientation was driven by
      interactions of the design with the eye's optical aberrations. FINANCIAL
      DISCLOSURE: None of the authors has a financial or proprietary interest in any
      material or method mentioned.

PMID- 27697246
TI  - Expanding binocular depth of focus by combining monovision with diffractive
      bifocal intraocular lenses.
AB  - PURPOSE: To test the hypothesis that binocular depth of field can be expanded
      while retaining high-quality vision at intermediate distances by combining
      anisometropia (monovision) and simultaneous vision bifocals. SETTING: School of
      Optometry, Indiana University, Bloomington, Indiana, USA. DESIGN: Prospective
      research study. METHODS: A computational polychromatic model was used to simulate
      retinal images as seen through a pseudophakic eye with a diffractive bifocal for
      a range of target distances. Computationally blurred stimuli were presented
      dichoptically, simulating a binocular pseudophakic person with 1 emmetropic eye
      and 1 eye with myopia of 0.40 diopter (D), 0.80 D, or 1.20 D. Binocular visual
      acuity was measured for computationally blurred high-contrast Sloan letters.
      RESULTS: Ten subjects participated in this study. The emmetropic eye achieved
      best vision at infinity and near distance specified by the addition (add) power,
      while the myopic eye peak acuities were achieved at shorter viewing distances.
      Having 1 myopic bifocal eye had no effect on distance acuities. With a bifocal
      add of 2.20 D and 1.20 D of anisometropia, the binocular depth of focus was more
      than 3.00 D and provided binocular acuities of better than 20/20 throughout this
      range. For each target distance, the binocular acuities closely approached those
      of the better-focused eye. CONCLUSIONS: By careful selection of unilateral myopia
      and bilateral use of high-quality bifocal lenses, high intermediate distance
      acuities can exist with a large depth of field. This approach can improve
      intermediate vision and expand depth of field without compromising best
      achievable distance and near acuities. FINANCIAL DISCLOSURE: None of the authors
      has a financial or proprietary interest in any material or method mentioned.

PMID- 27697247
TI  - Effect of cataract surgery training on operating room productivity: How long
      trainees take.
AB  - PURPOSE: To determine the effect of specialty training on cataract operation
      times and operating room efficiency. SETTING: Manchester Royal Eye Hospital,
      Manchester, United Kingdom. DESIGN: Retrospective consecutive case series.
      METHODS: Specialty training and consultant case times with preparation times were
      recorded between August 2014 and May 2015. Cases with posterior capsule rupture
      requiring anterior vitrectomy or iris hook insertion were analyzed. RESULTS: The
      study reviewed 1904 cases (906 consultant cases, 797 specialty training cases).
      Trainees' case time was significantly longer than consultants' (mean 24.25
      minutes +/- 12.36 [SD] versus 19.59 +/- 10.05 minutes) (P < .0001). The
      difference between the 1- to 3-year trainees' mean surgical time and 4- to 7-year
      trainees' mean surgical time was statistically significant (P < .0001). Mean case
      time decreased from 27.63 +/- 12.57 minutes (1- to 3-year trainees) to 22.55 +/-
      11.90 minutes (4- to 7-year trainees). The mean posterior capsule rupture rate
      was 2.76% for trainees and 1.77% for consultants. When posterior capsule rupture
      occurred, the mean surgical time increased to 49.81 +/- 18.69 minutes for the
      consultant group and 67.00 +/- 26.26 minutes for the trainee group (P = .024).
      When iris hooks were required, the mean case time was 26.41 +/- 11.28 minutes and
      34.11 +/- 15.06 minutes, respectively (P = .026). CONCLUSIONS: Specialty training
      cases had a longer duration than consultant cases, although the mean surgical
      time decreased with increased trainee experience. After 3 years of training,
      trainees did not have a significant effect on operating room efficiency.
      FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest
      in any material or method mentioned.

PMID- 27697248
TI  - Outcomes of topography-guided versus wavefront-optimized laser in situ
      keratomileusis for myopia in virgin eyes.
AB  - PURPOSE: To compare the outcomes of topography-guided and wavefront-optimized
      treatment in patients having laser in situ keratomileusis (LASIK) for myopia.
      SETTING: Advanced Eye Centre, Post Graduate Institute of Medical Education and
      Research, Chandigarh, India. DESIGN: Prospective contralateral-eye case study.
      METHODS: Patients had topography-guided LASIK in 1 eye and wavefront-optimized
      LASIK in the contralateral eye using the Customized Refractive Surgery Master
      software and Mel 80 excimer laser. Refractive (residual manifest refraction
      spherical equivalent [MRSE], higher-order aberrations [HOAs]), and visual
      (uncorrected distance visual acuity [UDVA] and photopic and mesopic contrast
      sensitivity) outcomes were prospectively analyzed 6 months postoperatively.
      RESULTS: The study comprised 35 patients. The UDVA was 0.0 logMAR or better and
      the postoperative residual MRSE was +/-0.50 diopter in 94.29% of eyes in the
      topography-guided group and 85.71% of eyes in the wavefront-optimized group (P =
      .09). More eyes in the topography-guided group than in the wavefront-optimized
      group had a UDVA of -0.1 logMAR or better (P = .04). Topography-guided LASIK was
      associated with less deterioration of mesopic contrast sensitivity at higher
      spatial frequencies (12 cycles per degree [cpd] and 18 cpd) and lower amounts of
      induced coma (P = .04) and spherical aberration (P = .04). Less stromal tissue
      was ablated in the topography-guided group (mean 61.57 MUm +/- 16.23 [SD]) than
      in the wavefront-optimized group (mean 79.71 +/- 14.81 MUm) (P < .001).
      CONCLUSION: Although topography-guided LASIK and wavefront-optimized LASIK gave
      excellent results, topography-guided LASIK was associated with better contrast
      sensitivity, lower induction of HOAs, and a smaller amount of tissue ablation.
      FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest
      in any material or method mentioned.

PMID- 27697249
TI  - Ocular flora and their antibiotic susceptibility in patients having cataract
      surgery in Italy.
AB  - PURPOSE: To characterize the ocular flora in a consecutive group of patients
      having cataract surgery and to determine the antibiotic susceptibility profile of
      isolates to several ophthalmic antibiotics. SETTING: Hospital Di Stefano,
      Catania, Italy. DESIGN: Observational case series. METHODS: Conjunctival and
      eyelid cultures from patients were obtained 14 days before surgery and, if
      positive, repeated the day of the surgery. Antimicrobial susceptibility for
      aminoglycosides (netilmicin and tobramycin), fluoroquinolones (ofloxacin,
      levofloxacin, and moxifloxacin), chloramphenicol, and azithromycin was tested
      using the Kirby-Bauer disk diffusion method. Susceptibility was also tested for
      oxacillin, cefuroxime, and vancomycin. All positive patients received a 2-day
      preoperative course of 3 mg/mL netilmicin ophthalmic solution 4 times a day. The
      recovery rate of microorganisms after antibiotic treatment compared with baseline
      was calculated. RESULTS: One hundred twenty consecutive patients were included in
      the study. Cultures were positive in 72.5% of patients; 131 isolates, mainly gram
      positive, were identified. Staphylococcus epidermidis (58.0%) and Staphylococcus
      aureus (15.3%) were the most frequently isolated microorganisms. Methicillin
      resistant staphylococci accounted for 3.8% of S epidermidis and 20.0% of S
      aureus. A high in vitro susceptibility (>90%) for all isolates, including
      multiresistant coagulase-negative Staphylococcus, was obtained for netilmicin,
      vancomycin, and cefuroxime. The recovery rate of isolates before surgery was
      reduced by 93.9% (P < .001). CONCLUSIONS: Conjunctival and lid margin isolates
      were sensitive to netilmicin, vancomycin, and cefuroxime. Microorganisms were
      less susceptible to other ophthalmic antibiotics, with the exception of
      moxifloxacin. A 2-day preoperative course with topical netilmicin reduced most
      bacteria identified on the conjunctiva and eyelids. FINANCIAL DISCLOSURE: Dr.
      Papa and Ms. Blanco are employees of Societa Industria Farmaceutica Italiana SpA.
      Dr. Santocono has no financial or proprietary interest in any material or method
      mentioned.

PMID- 27697250
TI  - Endophthalmitis after cataract surgery despite intracameral antibiotic
      prophylaxis with licensed cefuroxime.
AB  - PURPOSE: To report a case series of post-phacoemulsification endophthalmitis
      despite antibiotic prophylaxis with an intracameral injection of a licensed
      cefuroxime formulation (Aprokam). SETTING: University Hospitals of Pointe-a
      Pitre, Guadeloupe, and Fort-de-France, Martinique, French West Indies. DESIGN:
      Retrospective case series. METHODS: Patients who had cataract surgery with
      licensed cefuroxime prophylaxis between March 1, 2013, and July 31, 2015, and
      developed endophthalmitis were included. Bacteriologic findings and final
      corrected distance visual acuity 6 months after treatment were collected.
      RESULTS: Five patients developed endophthalmitis within 15 days after surgery,
      which was performed in different settings by different cataract surgeons. All
      patients had no-stich cataract surgery. Surgery was uneventful in 4 cases. One
      patient had a posterior capsule rupture. An anterior chamber paracentesis with
      analysis of the aqueous humor was performed to confirm endophthalmitis.
      Bacteriologic tests showed alpha-hemolytic streptococcus in 2 cases,
      Staphylococcus epidermidis in 1 case, and Serratia marcescens in 1 case. Two
      strains of bacteria showed cefuroxime resistance on the antibiogram. Despite
      parenteral and intravitreal injections of antibiotics, 4 of 5 cases had a poor
      outcome, with a visual acuity of less than 20/200. Retinal detachment (RD) was
      the most frequent complication observed in the following months. CONCLUSIONS:
      Although licensed cefuroxime has proven to be efficient in reducing the incidence
      of endophthalmitis, it has not eradicated this potentially severe complication of
      cataract surgery. Endophthalmitis occurring after the use of licensed cefuroxime
      can still result in very poor visual outcomes related to the infection itself or
      to its delayed complications such as RD. FINANCIAL DISCLOSURE: None of the
      authors has a financial or proprietary interest in any material or method
      mentioned.

PMID- 27697251
TI  - Late postoperative opacification of a hydrophilic-hydrophobic acrylic intraocular
      lens.
AB  - PURPOSE: To report late postoperative opacification of a model of hydrophilic
      hydrophobic acrylic intraocular lens (IOL) as well as the clinical consequences
      and laboratory characteristics. SETTING: Department of Ophthalmology, Centro
      Hospitalar e Universitario de Coimbra, Coimbra, Portugal. DESIGN: Retrospective
      case series. METHODS: Medical records were reviewed of patients with Lentis LS
      502-1 IOL opacification reporting visual loss who had IOL explantation between
      November 2013 and March 2015. Patients were identified in the emergency room or
      during regular follow-up visits. Explanted IOLs were analyzed at the Ophthalmic
      Explants Biobank, Vissum, Spain, or at the John A. Moran Eye Center, University
      of Utah, USA. RESULTS: Twenty opacified IOLs were explanted from 19 patients. The
      mean interval between cataract surgery and diagnosis of opacification was 29.15
      months +/- 9.57 (SD) (range 6 to 45 months). Opacification led to a statistically
      significant reduction in corrected distance visual acuity (mean 0.86 +/- 0.76
      logMAR; P < .001) and occurred in 5.1% of the hydrophilic-hydrophobic acrylic
      IOLs implanted at the department. The most frequently associated medical
      conditions were arterial hypertension, diabetes, and glaucoma. All IOLs but 1 had
      a similar pattern of opacification, with yellowish diffuse opacification
      uniformly distributed and calcium deposits on the surface and/or subsurface of
      the optic and haptics and within the IOL material. CONCLUSIONS: Opacification of
      the hydrophilic-hydrophobic acrylic IOL was found in a significant number of
      patients and had a significant effect on their vision. The opacification was
      attributed to primary calcification. FINANCIAL DISCLOSURE: None of the authors
      has a financial or proprietary interest in any material or method mentioned.

PMID- 27697252
TI  - Outcomes after combined phacoemulsification and trabecular microbypass stent
      implantation in controlled open-angle glaucoma.
AB  - PURPOSE: To study the effect of combined phacoemulsification cataract surgery and
      iStent (trabecular microbypass stent) implantation on intraocular pressure (IOP)
      and medication use in open-angle glaucoma (OAG) patients with a low mean
      preoperative IOP. SETTING: University of Colorado Health Eye Center, Aurora,
      Colorado, USA. DESIGN: Retrospective case series. METHODS: Treatment outcomes
      analyzed included IOP, medication use, and corrected distance visual acuity
      (CDVA). Treatment success was defined as a 20% or more IOP reduction or
      discontinuation of at least 1 medication. RESULTS: Sixty-four eyes of 45 patients
      were included in the analysis. At 1 year, the mean IOP was significantly reduced
      from 14.7 +/- 3.2 mm Hg (SD) to 13.2 +/- 2.8 mm Hg (P < .01) and the mean
      medication use decreased from 1.81 +/- 1.13 to 1.41 +/- 1.48 (P = .0001). The
      estimated IOP reduction at 1, 3, 6, and 12 months was 3.5% (P = .23), 7.9% (P =
      .04), 9.7% (P = .01), and 12.2% (P = .002), respectively. Treatment success at 1
      year was achieved in 76.1% of patients, and 41% of patients were medication free
      at 1 year. The CDVA was significantly improved from 0.4 +/- 0.38 logMAR at
      baseline to 0.17 +/- 0.35 at 1 year (P < .0001). CONCLUSIONS: Combined cataract
      surgery and trabecular microbypass stent implantation was statistically effective
      in reducing IOP and/or medication burden in OAG patients with a low preoperative
      IOP. During the informed surgical consent process, the physician and patient
      should consider the clinical benefit of modest IOP lowering and/or a decrease in
      medication use. FINANCIAL DISCLOSURE: Drs. Seibold, SooHoo, Pantcheva, and Kahook
      have received grant support from Glaukos Corp. No other author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 27697253
TI  - Primary posterior capsulotomy in femtosecond laser-assisted cataract surgery: In
      vivo spectral-domain optical coherence tomography study.
AB  - PURPOSE: To evaluate whether the size of Berger space is safely predictable in
      patients having cataract surgery using 3-dimensional spectral-domain optical
      coherence tomographic (3-D SD-OCT) image analysis. SETTING: Ruhr University Eye
      Hospital, Bochum, Germany. DESIGN: Prospective interventional case series.
      METHODS: Eyes having routine femtosecond laser-assisted cataract surgery were
      included. After wound closure, the anterior eye segment was visualized using the
      incorporated 3-D SD-OCT. Visualization of Berger space was performed in the axial
      and sagittal planes. RESULTS: The study comprised 165 consecutive eyes. In 155
      eyes, 3-D SD-OCT visualized Berger space and its dimensions were analyzed. In 72%
      of the cases, Berger space was large enough to perform a femtosecond laser
      assisted primary posterior capsulotomy. In 24 eyes (15.5%) with a minimum axial
      length of 25.0 mm, Berger space was 500 MUm or larger. CONCLUSION: Femtosecond
      laser systems incorporating real-time SD-OCT allowed direct visualization of
      Berger space intraoperatively, providing surgeons with the information needed to
      safely create posterior capsulotomies after intraocular lens implantation.
      FINANCIAL DISCLOSURE: Dr. Dick is a consultant to Abbott Medical Optics, Inc. No
      other author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 27697254
TI  - Comparison of different types of phacoemulsification tips. I. Quantitative
      analysis of elemental composition and tip surface microroughness.
AB  - PURPOSE: To evaluate the elemental composition of phacoemulsification tips and
      their surface roughness in the microscale. SETTING: John A. Moran Eye Center and
      Utah Nanofab, College of Engineering, University of Utah, Salt Lake City, Utah,
      USA. DESIGN: Experimental study. METHODS: Seven types of phacoemulsification tips
      were studied. The phaco tips were examined through energy-dispersive x-ray
      spectroscopy (EDS) and x-ray photoelectron spectroscopy (XPS) for elemental
      composition. In addition, the roughness of the opening in all tips was assessed
      through 3-dimensional white-light interferometry. RESULTS: Elemental analysis
      showed considerable differences in the surface layers between manufacturers.
      Alcon tips had a thinner oxidized titanium (Ti) layer in their surface. Through
      XPS, vanadium was not detected in the superficial layers of any tip, but only in
      deeper levels. The microroughness surface analysis showed comparable results
      regarding their root-mean-square (RMS) metric. Maximum peak valley distance
      values varied and appeared to be dependent on the quality of material process
      rather than the material itself. CONCLUSIONS: Phacoemulsification tips are made
      of Ti alloys and showed differences between models, especially regarding their
      composition in the superficial layers. Their opening end roughness showed an
      overall appropriate RMS value of less than 1.0 MUm in all cases. The existence of
      small defected areas highlights the importance of adequate quality control of
      these critical surgical instruments. FINANCIAL DISCLOSURE: None of the authors
      has a financial or proprietary interest in any material or method mentioned.

PMID- 27697255
TI  - Comparison of different types of phacoemulsification tips. II. Morphologic
      alterations induced by multiple steam sterilization cycles with and without use
      of enzyme detergents.
AB  - PURPOSE: To evaluate the alterations in the morphology and elemental composition
      of reusable phacoemulsification tips after cleaning and sterilization. SETTING:
      John A. Moran Eye Center, Salt Lake City, Utah, USA. DESIGN: Experimental study.
      METHODS: For the main experiment, 2 types of reusable phacoemulsification needles
      were studied. One tip of each type underwent 1, 2, and 3 autoclave sterilizations
      with the use of detergents followed by thorough rinsing with sterile water
      between cycles. Another set of tips underwent the same procedure but without
      rinsing. Subsequently, phaco tips were examined through scanning electron
      microscopy and energy-dispersive x-ray spectroscopy to assess morphologic changes
      and surface deposits. In a second experiment, tips of 8 different types (both
      reusable and single use) underwent 10 sterilization autoclave cycles without
      detergents. RESULTS: Residues, mostly comprised of carbon-containing material,
      were found in extensive areas of tips that were sterilization with enzymes and
      without rinsing. Smaller and fewer residues were found in tips after
      sterilization with the use of enzymes and thorough rinsing. Tips that underwent
      autoclave sterilization without detergents had no bulky deposits on their
      surface; they mostly had thin layers of sodium and chloride or material
      discoloration. CONCLUSIONS: Rinsing the phaco tips significantly reduced the size
      and number of residues after use of enzymatic detergents. However, detergent
      residues were detected on phaco tip surfaces even after thorough rinsing with
      sterile water. No major noticeable changes were observed in either single-use or
      reusable phaco tips after 10 cycles of sterilization without detergents.
      FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest
      in any material or method mentioned.

PMID- 27697256
TI  - Optical bench performance of 3 trifocal intraocular lenses.
AB  - PURPOSE: To compare the optical performance of 3 trifocal intraocular lenses
      (IOLs): the Acrysof IQ Panoptix (+2.17 diopter [D]/+3.25 D IOL), AT LISA Tri
      839MP (+1.66 D/+3.33 D IOL), and Finevision Micro F (+1.75 D/+3.50 D IOL).
      SETTING: Alcon Research Ltd., Fort Worth, Texas, USA. DESIGN: Experimental study.
      METHODS: The 3 trifocal IOLs were compared using optical performance tests. To
      measure image quality, through-focus modulation transfer function (MTF) curves
      were generated for a model eye. To assess resolution, through-focus Badal images
      of an Early Treatment Diabetic Retinopathy Study chart simulating viewing
      distances of infinity to 40 cm were recorded. To measure photic phenomena,
      simulated headlight images with a 50 MUm pinhole target and a 5.0 mm pupil were
      obtained. RESULTS: The MTF measurements showed similar near and distance peaks
      for the IOLs, but the optimum intermediate peak for the +2.17 D/+3.25 D IOL was
      60 cm versus 80 cm for the other 2 trifocal IOLs. Similarly, in bench Badal image
      testing, the optimum intermediate image was at 60 cm for the +2.17 D/+3.25 D IOL
      and 80 cm for the other 2 IOLs. Overall, halos surrounding simulated headlight
      images were equivalent for the 3 IOLs. CONCLUSIONS: In bench studies, the new
      +2.17 D/+3.25 D trifocal IOL showed equivalent or better performance in image
      quality, resolution, and photic phenomena compared with the +1.66 D/+3.33 D and
      +1.75 D/+3.50 D trifocal IOLs. The new IOL is expected to provide better
      intermediate vision at 60 cm, which is preferred for real-life tasks such as
      computer work, over the 80 cm intermediate distance offered by the other 2
      trifocal IOLs. FINANCIAL DISCLOSURE: All authors are employees of Alcon Research,
      Ltd.

PMID- 27697258
TI  - Chronic postoperative fungal endophthalmitis caused by Penicillium citrinum after
      cataract surgery.
AB  - : An 85-year-old man developed chronic postoperative endophthalmitis after
      complicated cataract surgery. Visual acuity in the affected eye was hand
      movements. Slitlamp biomicroscopy showed a hypopyon, superonasal iris nodule, and
      marked vitritis. An anterior chamber washout, iris biopsy, and intravitreal
      amphotericin injection were performed. Panfungal polymerase chain reaction of
      anterior chamber and vitreous samples were positive for Penicillium citrinum. The
      iris biopsy showed hyphae on Grocott staining. Despite treatment, the patient's
      acuity deteriorated to light perception and he developed severe intractable pain
      requiring evisceration. Histological analysis showed diffuse infiltration of
      hyphae. Penicillium species are fungal organisms that are ubiquitous in the
      environment and can cause chronic endophthalmitis. They are commonly dismissed as
      culture contaminants. True infection is confirmed by histological demonstration
      of fungal invasion. Diagnosis can be aided by iris biopsy if iris nodules are
      present. Polymerase chain reaction testing was beneficial in identifying the
      causative organism and should be considered early in endophthalmitis cases.
      Despite intravitreal and systemic antifungal treatment, the visual prognosis for
      this condition is variable. FINANCIAL DISCLOSURE: None of the authors has a
      financial or proprietary interest in any material or method mentioned.

PMID- 27697257
TI  - Cataract surgery and nonsteroidal antiinflammatory drugs.
AB  - : Nonsteroidal antiinflammatory drugs (NSAIDs) have become an important
      adjunctive tool for surgeons performing routine and complicated cataract surgery.
      These medications have been found to reduce pain, prevent intraoperative miosis,
      modulate postoperative inflammation, and reduce the incidence of cystoid macular
      edema (CME). Whether used alone, synergistically with steroids, or for specific
      high-risk eyes prone to the development of CME, the effectiveness of these
      medications is compelling. This review describes the potential preoperative,
      intraoperative, and postoperative uses of NSAIDs, including the potency,
      indications and treatment paradigms and adverse effects and contraindications. A
      thorough understanding of these issues will help surgeons maximize the
      therapeutic benefits of these agents and improve surgical outcomes. FINANCIAL
      DISCLOSURE: Proprietary or commercial disclosures are listed after the
      references.

PMID- 27697259
TI  - Pressures generated during corneal wound hydration.

PMID- 27697260
TI  - Quality-of-vision symptoms after small-incision lenticule extraction: September
      consultation #1.

PMID- 27697261
TI  - September consultation #2.

PMID- 27697262
TI  - September consultation #5.

PMID- 27697263
TI  - September consultation #4.

PMID- 27697264
TI  - September consultation #3.

PMID- 27697265
TI  - September consultation #7.

PMID- 27697266
TI  - September consultation #6.

PMID- 27697267
TI  - September consultation #8.

PMID- 27697268
TI  - Confusion about the importance of phaco tip configuration in comparing machine
      performance.

PMID- 27697269
TI  - Effect of an intact posterior capsule on visual function after cataract surgery.

PMID- 27697270
TI  - Reply.

PMID- 27697271
TI  - Trajectories and predictors of state and trait anxiety in patients receiving
      chemotherapy for breast and colorectal cancer: Results from a longitudinal study.
AB  - PURPOSE: To examine the trajectories and predictors of state and trait anxiety in
      patients undergoing chemotherapy for breast or colorectal cancer. METHODS:
      Secondary analysis of data collected as part of a large multi-site longitudinal
      study. Patients with breast or colorectal cancer completed validated scales
      assessing their state and trait anxiety levels (State-Trait Anxiety Inventory)
      and symptom burden (Rotterdam Symptom Checklist) at the beginning of each
      chemotherapy cycle. Longitudinal mixed model analyses were performed to test
      changes of trait and state anxiety over time and the predictive value of symptom
      burden and patients' demographic (age, gender) and clinical characteristics
      (cancer type, stage, comorbidities, ECOG performance status). RESULTS: Data from
      137 patients with breast (60%) or colorectal cancer (40%) were analysed. Linear
      time effects were found for both state (chi2 = 46.3 [df = 3]; p < 0.001) and
      trait anxiety (chi2 = 17.708 [df = 3]; p = 0.001), with anxiety levels being
      higher at baseline and gradually decreasing over the course of chemotherapy.
      Symptom burden (beta = 0.21; SD = 0.06; p = 0.001) predicted state anxiety
      throughout treatment, but this effect disappeared when accounting for trait
      anxiety scores before the start of chemotherapy (beta = 0.85; SD = 0.05; p <
      0.001). Patients' baseline trait anxiety was the only significant predictor of
      anxiety throughout treatment. CONCLUSIONS: Changes in the generally stable
      characteristic of trait anxiety indicate the profoundly life-altering nature of
      chemotherapy. The time point before the start of chemotherapy was identified as
      the most anxiety-provoking, calling for interventions to be delivered as early as
      possible in the treatment trajectory. Patients with high trait anxiety and
      symptom burden may benefit from additional support.

PMID- 27697272
TI  - The influence of symptoms on quality of life among patients who have undergone
      oesophageal cancer surgery.
AB  - PURPOSE: After oesophagectomy, anatomical changes and loss of function induce
      various symptoms that may affect quality of life (QoL) in oesophageal cancer
      patients. The purpose of this study was to identify the factors influencing QoL
      in Korean patients who have undergone oesophageal cancer surgery. METHOD: This
      was a cross-sectional study of a convenience sample consisting of 120 surgery
      patients with oesophageal cancer. We used the EORTC QLQ-C30 and EORTC QLQ-OES18
      to measure participants' oesophageal cancer-related symptoms and QoL. Multiple
      regression analyses were applied to analyse to the relationship between cancer
      related symptoms and QoL. RESULTS: The average score of oesophageal cancer
      related symptoms was 19.28 points, and the most common symptom was reflux. The
      mean score for global health status/QoL was 60.55. There were significant
      differences in the functional and symptom subscales according to financial
      burden, operation type (procedure), and treatment period. Dysphagia most affected
      global health status/QoL, and eating problems most affected the functional and
      symptom subscales. CONCLUSION: Dysphagia and eating problems were confirmed to be
      the most common symptoms affecting the QoL of patients who had undergone
      oesophageal cancer surgery. These results can be used to aid in the development
      of strategies to better manage symptoms in these patients.

PMID- 27697273
TI  - Continuing variation and barriers to nurse-led vaginal dilator education for
      women with gynaecological cancer receiving radiotherapy.

PMID- 27697274
TI  - Disability and quality of life in community-dwelling elderly cancer survivors:
      Case-control study in the Korean population.
AB  - PURPOSE: Advanced age is a significant risk factor for cancer and functional
      disabilities increase with age. The purpose of this case-control study of Korean
      individuals was to determine the effect of cancer and cancer treatment on
      functional disability and quality of life (QOL). Thus, we compared community
      dwelling elderly cancer patients (ECPs) with individuals from the general elderly
      population (GEP) who never had diagnoses of cancer. METHODS: We selected 1776 ECP
      who were at least 65 years-old from the 2008 Korean Community Health Survey data
      and used propensity score matching to randomly select 1766 individuals from the
      GEP who closely resembled the ECPs. Functional disability was measured using the
      Instrumental Activities of Daily Living (IADL) scale, and QOL was measured by the
      EuroQol Group EQ-5D. RESULTS: ECPs were more dependent in preparation of food,
      doing laundry, and shopping (IADL scale), and in mobility and usual activities
      (EQ-5D). Although ECP had more problems with pain, discomfort, anxiety, and
      depression, they were more independent in self-care and handling of financial
      responsibilities. CONCLUSIONS: ECPs had multiple physical and psychological
      symptoms that adversely affected functional disability and QOL, but higher
      functional ability, such as self-care and handling of financial responsibilities.
      Promotion of self-care by ECPs is pivotal for effective management in community
      practice.

PMID- 27697275
TI  - Development of the Head and Neck Cancer Caregiving Task Inventory.
AB  - PURPOSE: Family caregivers provide vital support for patients with head and neck
      cancer (HNC), yet few studies have focused on HNC caregiving. Our objective was
      to develop and conduct initial validation of the HNC Caregiving Task Inventory,
      an instrument to characterize caregiving task burden in the HNC population.
      METHODS: This 5-phase instrument development project involved the
      conceptualization of caregiving task burden (Phase 1), initial instrument
      development (Phase 2), assessment of content validity through expert panel review
      (Phase 3), assessment of face validity through family caregiver review (Phase 4),
      and preliminary validation in a sample of 106 family caregivers (Phase 5).
      RESULTS: We identified 11 domains of the HNC caregiving role and caregiving tasks
      for each domain. In Phase 3, the experts deemed all tasks relevant to HNC family
      caregiving. No tasks were eliminated and 19 were added. In Phase 4, family
      caregiver feedback indicated that the tasks were comprehensive and relevant.
      Wording and formatting changes were made and one task was added. In Phase 5, we
      evaluated discrimination of responses to derive a final version comprised of 58
      tasks in 11 domains. Kuder-Richardson values for domains with >=3 items ranged
      from 0.65 to 0.94. Associations were generally high with the Caregiving Burden
      Scale, moderate with the Caregiver Reaction Assessment and Profile of Mood States
      Short Form, and low or non-existent with the Preparedness Scale. CONCLUSION:
      Convergent and divergent validity were supported. The HNC Caregiving Task
      Inventory can be used to evaluate caregiving task burden across the treatment
      trajectory and identify targets for intervention.

PMID- 27697276
TI  - Understanding the experiences of adolescents and young adults with cancer: A meta
      synthesis.
AB  - PURPOSE: To conduct a meta-synthesis of qualitative studies exploring experiences
      of young cancer patients to identify the overarching concepts that inform future
      service and research directions. METHOD: A systematic literature search was
      conducted, and 51 articles published between January 2004 and March 2014 were
      collected via CINAHL, Medline and PsycINFO databases. Deductive thematic analysis
      was conducted to identify major themes, guided by Hermeneutic notions on
      interpretation. RESULTS: Cancer impacted a wide range of life domains. These
      impacts were interconnected and bi-directional. The meanings of these impacts
      were closely related to their unique developmental needs and a social position as
      youth. Emotional struggles during these radical changes were evident, but efforts
      to make sense of their experiences and find meaning pervaded. CONCLUSIONS: Given
      the interrelated nature of the cancer challenges young cancer patients
      experience, there needs to be an emphasis on conducting studies which further
      refine our understanding of these relationships. This can help to structure
      effective youth cancer services. Generic informational resources and support
      services should be tailored so that they have relevance to the young person's
      life context. The treating team has an important role in fostering young
      patients' ability to make sense of their experiences by providing developmentally
      relevant psychosocial support.

PMID- 27697277
TI  - Existential challenges in young people living with a cancer diagnosis.
AB  - PURPOSE: In Sweden, approximately 500 people between the ages of 15 and 39 are
      diagnosed with cancer each year. When someone is diagnosed with a life
      threatening disease, existential issues are easily triggered. Young adults are in
      a developmental phase of life and are exposed to an extra amount of pressure. The
      Internet and social media are a daily part of the life of young adults and the
      use of blogs is common. The aim of this study was to elucidate the theoretical
      framework of Yalom and his four 'givens' expressed in blogs written by young
      adults living with various cancer diagnoses in Sweden. METHOD: This study used a
      qualitative method in which written stories from six public blogs were analysed
      using qualitative content analysis. RESULTS: The findings offer valuable in-depth
      knowledge about the existential issues in this population. The results can be
      described as a journey with several existential challenges and with death as an
      impending threat. The bloggers' awareness of their mortality was described as
      creating a sense of loss and existential loneliness. CONCLUSIONS: This study
      shows that young adults are empowered by the writing of blogs and that blogs can
      play an important part in increasing wellbeing and a sense of coherence within
      this population.

PMID- 27697278
TI  - Addressing behavioral impacts of childhood leukemia: A feasibility pilot
      randomized controlled trial of a group videoconferencing parenting intervention.
AB  - PURPOSE: Child emotional and behavioral problems constitute significant sequelae
      of acute lymphoblastic leukemia (ALL) treatment. The aims of this study were to
      a) examine the feasibility, acceptability and satisfaction of a parenting
      intervention amongst parents of children with ALL and b) explore whether
      participation in a parenting intervention shows promise for improvements in child
      behavior. METHODS: 12 parents with a child aged between 2 and 8 years receiving
      maintenance phase treatment for ALL participated in a phase 2 randomized
      controlled trial comparing eight weeks of group online participation in Triple P:
      Positive Parenting Program with no intervention. RESULTS: The number of eligible
      parents who completed the intervention was low (31.6%). Main reasons for non
      consent or dropout were program time commitment too high or content not relevant.
      For parents who completed the intervention, satisfaction and acceptability was
      high. Parents reported the intervention as highly relevant and topical, feasible,
      helpful and a positive experience. Results indicated a non-significant trend
      towards improved total child behavioral and emotional difficulties following the
      intervention. Qualitative results indicated that intervention group parents
      reported improvements in parenting skills and competence, and decreased child
      behavioral problems. CONCLUSIONS: These pilot data highlight the difficulties of
      engaging and retaining parents in an 8-week parenting intervention in this
      context. For parents who completed the intervention, results indicated high
      feasibility, acceptability and satisfaction. Suggestions for further research and
      intervention modifications are provided to enhance uptake and strengthen efforts
      to assist parents in addressing child behavioral and emotional challenges during
      ALL treatment.

PMID- 27697279
TI  - Specialist nurse key worker in children's cancer care: Professionals'
      perspectives on the core characteristics of the role.
AB  - PURPOSE: To describe the development and implementation of the specialist nurse
      key worker role across 18 children's cancer centres in the United Kingdom, and
      draw out significant factors for success to inform future development of the role
      across a range of specialities. METHOD: Data were obtained through 42 semi
      structured interviews and a focus group with 12 key workers. Framework analysis
      revealed two main themes: models of care and key workers' perspectives of the
      role. RESULTS: Four models of care were identified and described, roles were
      organised along a continuum of in reach and outreach with either the presence or
      absence of home visits and direct delivery of clinical care. Key workers'
      perspectives of the advantages of the role included: coordination of care (being
      the main point of contact for families/professionals), experience and expertise
      (communication/information) and the relationship with families. The main
      challenges identified were: time, caseload size, geographical area covered,
      staffing numbers and resources available in the hospital and community.
      CONCLUSION: The label 'key worker' was disliked by many participants, as the loss
      of 'specialist nurse' in the title failed to reflect professional group. Leaving
      aside terminology, key workers shared core role elements within a continuum of in
      reach and outreach work and their involvement in direct clinical care varied
      throughout the pathway. Irrespective of the model they worked in, the key worker
      provided clinical, emotional, educational, and practical support to families,
      through the coordination of care, experience and expertise and relationship with
      families and professionals.

PMID- 27697280
TI  - The lived experience of patients in protective isolation during their hospital
      stay for allogeneic haematopoietic stem cell transplantation.
AB  - PURPOSE: Patients undergoing allogeneic haematopoietic stem cell transplantation
      (HSCT) usually receive hospital care in protective isolation until full
      neutrophil recovery. Although the aim of protective isolation is to benefit
      patients' health by preventing risks of infection, it could have severe
      psychological implications. The aim of this study was to explore the lived
      experiences of protective isolation in adult patients who had been treated with
      allogeneic HSCT. METHOD: A descriptive phenomenological inquiry based on Giorgi's
      approach was conducted in a university hospital in Italy. Ten patients (7 female
      and 3 male, age range 28-66), who had undergone allogeneic HSCT to treat a
      haematological malignancy, were interviewed about their hospital stay in
      protective isolation. RESULTS: A general meaning structure was identified as
      being isolated to achieve transformation. The revelatory themes were as follows:
      (1) the special place for transformation, (2) the experience of embodied
      transformation, and (3) light and shade from inside and outside. Participants
      experienced a transformation of themselves, of their relationships with loved
      ones, and of the environment. CONCLUSIONS: Since patients may live the experience
      of being treated with allogeneic HSCT in protective isolation as a transformation
      process, health-care providers should monitor the psychosocial implications of
      the isolation practice.

PMID- 27697281
TI  - The relationship between malignant wound status and pain in breast cancer
      patients.
AB  - PURPOSE: Skin metastasis is one of the most frequent metastases in breast cancer
      patients. Patients with malignant wounds experience numerous symptoms, including
      serious wound pain. However, the features of pain related to malignant wounds
      have not been investigated. Nurses can experience a dilemma when treating these
      patients due to a lack of knowledge of the pain. The aims of this study were to
      examine the quality and intensity of malignant wound pain and to determine the
      association between wound status and pain in the patients with malignant wounds.
      METHODS: Cross-sectional study was conducted. Participants were recruited from a
      breast centre based in a general hospital. We collected the patients' demographic
      and wound management data and assessed wound condition. Patients evaluated wound
      pain intensity and quality over the preceding week using the short-form McGill
      Pain Questionnaire (SF-MPQ). The association between SF-MPQ results, wound
      condition, and the time interval for wound care was evaluated using the
      Spearman's correlation coefficient. The protocol was approved by the Ethical
      Committee of the each facilities. RESULTS: The median age of the 22 enrolled
      patients was 61.5 years, and the median time after diagnosis of malignant wound
      was 15.5 months. Overall, 77.3% of patients complained of pain. Malignant wound
      pain significantly correlated with the degradation of wound edges, granulation
      tissue, and the time interval for wound care. CONCLUSION: We consider that it is
      necessary to provide pain-control care focused on the wound edge and granulation
      tissue of malignant wounds through the assessment of malignant wound pain and
      condition.

PMID- 27697282
TI  - How to get your research published.

PMID- 27697283
TI  - Effects of proximity to stormwater on the sandy-beach macrofaunal assemblages of
      metropolitan Adelaide, South Australia.
AB  - Stormwater run-off often enters coastal zones but its effects on sandy beaches
      are unknown. This study aimed to investigate associations between macrofaunal
      assemblages and proximity to stormwater outlets along Adelaide's beaches,
      comparing semi-natural creeks with concrete drains. Five positions along an
      increasing-salinity gradient were sampled in the intertidal zone of six
      stormwater outlets and also at corresponding control sites. There was no
      significant difference between the two forms of stormwater (semi-natural creeks
      with concrete drains). Only the largest outlet (Torrens) had a significant
      difference in assemblage structure and taxon richness compared to its control.
      Total abundances at this outlet followed a convex pattern across the salinity
      gradient, so it appears that flow there may have a spatially-limited positive
      effect on the macrofauna in terms of increasing abundance and richness.
      Therefore, the hypothesised detrimental effects of stormwater have not been found
      to be evident and these observed patterns warrant further investigation.

PMID- 27697284
TI  - Infection Dynamics of Foot-and-Mouth Disease Virus in Cattle Following
      Intranasopharyngeal Inoculation or Contact Exposure.
AB  - For the purpose of developing an improved experimental model for studies of foot
      and-mouth disease virus (FMDV) infection in cattle, three different experimental
      systems based on natural or simulated natural virus exposure were compared under
      standardized experimental conditions. Ante-mortem infection dynamics were
      characterized in cattle exposed to FMDV through a novel, simulated natural
      intranasopharyngeal (INP) inoculation system or through standardized and
      controlled systems of within- or between-species direct contact exposure (cattle
      to-cattle or pig-to-cattle). All three systems were efficient in causing
      synchronous, generalized foot-and-mouth disease in cattle exposed to one of three
      different strains of FMDV representing serotypes O, A and Asia1. There was more
      within-group variation in the timing of clinical infection following natural and
      simulated natural virus exposure systems when compared with the conventionally
      used system of needle inoculation (intraepithelial lingual inoculation). However,
      the three optimized exposure systems described herein have the advantage of
      closely simulating field conditions by utilizing natural routes of primary
      infection, thereby facilitating engagement of mucosal host defence mechanisms.
      Overall, it is concluded that INP inoculation and standardized systems of direct
      contact exposure provide effective alternatives to conventional (needle)
      inoculation systems for studies in which it is desirable to simulate the natural
      biology of FMDV infection.

PMID- 27697285
TI  - Vitamin D3 regulates LAMP3 expression in monocyte derived dendritic cells.
AB  - The family of lysosome-associated membrane proteins (LAMPs) encompassing LAMP1,
      LAMP2 and DC-LAMP (LAMP3) are the major constituents of the glycoconjugates coat
      present on the inside of the lysosomal membrane. LAMP3 is highly expressed only
      in certain cell types and during the differentiation stages. Its expression is
      linked the maturation of dendritic cells, inflammation, poor prognosis of certain
      tumors, and the locus where it is encoded was identified as a risk factor for
      Parkinson's disease (PD). Here, we investigated the capacity of Vitamin D3 to
      modulate the expression of LAMP3 during the dendritic cells differentiation and
      maturation. Our results demonstrated that the Vitamin D3 reduce the LAMP3
      mRNA/protein expression during the dendritic cells differentiation and
      maturation, via NFkappaB pathways. Furthermore, we demonstrated that the Vitamin
      D3 was able to modulate the expression of LAMP3 likewise to in vitro tolerogenic
      dendritic cells. In summary, these data showed that the decrease of LAMP3
      expression by Vitamin D3could enhance the tolerogenic characteristic of dendritic
      cells.

PMID- 27697286
TI  - The effect of transplanted human Wharton's jelly mesenchymal stem cells treated
      with IFN-gamma on experimental autoimmune encephalomyelitis mice.
AB  - Interferon gamma (IFN-gamma) increases the immunosuppressive property of human
      Wharton's jelly mesenchymal stem cells (hWJ-MSCs). In this study, we evaluated
      the therapeutic effects of IFN-gamma primed WJ-MSCs in EAE mice. IFN-gamma primed
      WJ-MSCs were injected on days 3 and 11 after EAE induction. 21 days after EAE
      induction, splenocytes and cervical lymph node cells were isolated and cell
      proliferation, secretion of inflammatory cytokines and frequency of regulatory T
      cells was measured. On day 50 of the study, cell infiltration and gene expression
      of inflammatory cytokines in brain of mice were studied. Leukocyte infiltration
      and symptoms were significantly reduced in IFN-gamma primed WJ-MSCs treated group
      compared to other groups. These cells showed significantly reduced proliferation
      and increased Treg cells as well as decreased secretion and gene expression of
      inflammatory cytokines in EAE mice. Our data suggest that IFN-gamma may be used
      to stimulate the immunomodulatory property of WJ-MSCs in clinical situations.

PMID- 27697287
TI  - The generalizability of NCI-sponsored clinical trials accrual among women with
      gynecologic malignancies.
AB  - OBJECTIVES: Enrollment of a representative population to cancer clinical trials
      ensures scientific reliability and generalizability of results. This study
      evaluated the similarity of patients enrolled in NCI-supported group gynecologic
      cancer trials to the incident US population. METHODS: Accrual to NCI-sponsored
      ovarian, uterine, and cervical cancer treatment trials between 2003 and 2012 were
      examined. Race, ethnicity, age, and insurance status were compared to the
      analogous US patient population estimated using adjusted SEER incidence data.
      RESULTS: There were 18,913 accruals to 156 NCI-sponsored gynecologic cancer
      treatment trials, ovarian (56%), uterine (32%), and cervical cancers (12%).
      Ovarian cancer trials included the least racial, ethnic and age diversity. Black
      women were notably underrepresented in ovarian trials (4% versus 11%). Hispanic
      patients were underrepresented in ovarian and uterine trials (4% and 5% versus
      18% and 19%, respectively), but not in cervical cancer trials (14 versus 11%).
      Elderly patients were underrepresented in each disease area, with the greatest
      underrepresentation seen in ovarian cancer patients over the age of 75 (7% versus
      29%). Privately insured women were overrepresented among accrued ovarian cancer
      patients (87% versus 76%), and the uninsured were overrepresented among women
      with uterine or cervical cancers. These patterns did not change over time.
      CONCLUSIONS: Several notable differences were observed between the patients
      accrued to NCI funded trials and the incident population. Improving
      representation of racial and ethnic minorities and elderly patients on cancer
      clinical trials continues to be a challenge and priority.

PMID- 27697288
TI  - Serum, uterine, and vaginal mucosal IgG antibody responses against Tritrichomonas
      foetus after administration of a commercial killed whole T foetus vaccine in beef
      cows.
AB  - The objective of this study was to determine the level and duration of IgG
      antibodies induced against killed whole Tritrichomonas foetus and T foetus
      purified surface antigen (TF1.17) in serum, vaginal, and uterine secretions after
      systemic immunization of beef cows with a vaccine containing killed whole T
      foetus. Twenty nonpregnant beef cows were randomly assigned to vaccine or control
      groups as follows: Vaccine (n = 10): cows received 2 mL of a commercial vaccine
      containing killed whole T foetus subcutaneously and a 2-mL booster 2 weeks later.
      Control (n = 10): cows received 2 mL of sterile saline on the same schedule.
      Vaginal secretions and blood samples were collected on Days 0, 8, 15, 22, 29, 36,
      43, 50, 60, 75, 89, 110, 146, and 182 relative to day of primary vaccination.
      Uterine flush fluid was collected on Days 0, 15, 29, and 43 after the day of
      primary vaccination. Samples were assayed for IgG antibodies to the killed whole
      T foetus and surface antigen TF1.17 using enzyme-linked immunosorbent assay.
      Serum whole T foetus-specific IgG levels were significantly increased (between
      Days 15 and 182) following vaccination with T foetus or with saline. No
      differences between vaccinates and controls in uterine responses to whole-cell
      antigen were detected. Serum anti-TF1.17 IgG responses to vaccination were
      significantly higher than Day 0 throughout the immunization period (P < 0.001)
      and were higher than responses in control animals on each day post immunization
      through Day 146 (P < 0.001). A significant rise in TF1.17-specific IgG levels was
      observed in vaginal and uterine fluids from Day 15 post vaccination compared to
      the Day 0 levels. These levels remained significantly elevated in vaginal and
      uterine fluids through Days 75 (P < 0.05) and 43 (P < 0.001) after primary
      vaccination, respectively. Antibody levels in serum, vaginal, and uterine
      secretions against TF1.17 remained low in the control group throughout the study.
      In conclusion, vaccination of beef cows with a commercial vaccine containing T
      foetus induced significant increase in the levels of IgG to the T foetus TF1.17
      surface antigen in serum, vaginal secretions, and uterine fluid, which remained
      elevated through Days 43, 75, and 182 in uterine fluids, vaginal secretions, and
      serum, respectively. Since purified TF1.17 antigen has been shown to protect
      against experimental T foetus infection in heifers, the vaccine-induced TF1.17
      specific IgG response is likely to be important in the prevention of
      trichomoniasis in beef cattle.

PMID- 27697289
TI  - Spontaneous Ca2+ transients in mouse microglia.
AB  - Microglia are the resident immune cells in the central nervous system and many of
      their physiological functions are known to be linked to intracellular calcium
      (Ca2+) signaling. Here we show that isolated and purified mouse microglia-either
      freshly or cultured-display spontaneous and transient Ca2+ elevations lasting for
      around ten to twenty seconds and occurring at frequencies of around five to ten
      events per hour and cell. The events were absent after depletion of internal Ca2+
      stores, by phospholipase C (PLC) inhibition or blockade of inositol-1,4,5
      trisphosphate receptors (IP3Rs), but not by removal of extracellular Ca2+,
      indicating that Ca2+ is released from endoplasmic reticulum intracellular stores.
      We furthermore provide evidence that autocrine ATP release and subsequent
      activation of purinergic P2Y receptors is not the trigger for these events.
      Spontaneous Ca2+ transients did also occur after stimulation with
      Lipopolysaccharide (LPS) and in glioma-associated microglia, but their kinetics
      differed from control conditions. We hypothesize that spontaneous Ca2+ transients
      reflect aspects of cellular homeostasis that are linked to regular and patho
      physiological functions of microglia.

PMID- 27697290
TI  - Laser generated nanoparticles based photovoltaics.
AB  - The exploitation of nanoparticles (NP), synthesized via laser ablation in
      liquids, in photovoltaic devices is reviewed. In particular, the impact of NPs'
      incorporation into various building blocks within the solar cell architecture on
      the photovoltaic performance and stability is presented and analysed for the
      current state of the art photovoltaic technologies.

PMID- 27697291
TI  - [Geographical distribution of mortality by Parkinson's disease and its
      association with air lead levels in Spain].
AB  - BACKGROUND AND OBJECTIVE: Parkinson's disease (PD) is the second most common
      neurodegenerative disease, and the etiology of its sporadic form is unknown. The
      present study analyzes the temporal and spatial variations of mortality by PD in
      Spain over a period of 14 years and its relationship with lead concentration
      levels in the atmosphere. METHOD: An ecological study was performed, in which
      deaths by PD and age group in 50 Spanish provinces between 2000 and 2013 were
      analyzed. The annual trend of PD mortality was assessed using the non-parametric
      Spearman's Rho test. Finally, the relationship between lead concentration levels
      in the air and mortality by PD was evaluated. RESULTS: Between 2000 and 2013,
      36,180 patients with PD died in Spain. There is an increasing trend in mortality
      through PD over the study period (P<.0001). La Rioja, Asturias, Basque Country
      and the Lower Ebro valley were the regions with the highest values of PD
      mortality. Those regions with the highest lead concentrations also showed higher
      mortality by this disease in people over 64 (P=.02). CONCLUSIONS: Over our period
      of study, there has been an increase in mortality through PD in Spain, with the
      northernmost half of the country registering the highest values. Mortality in men
      was higher than mortality in women. Moreover, a direct correlation was found
      between lead levels in the air and mortality through PD.

PMID- 27697292
TI  - Promotion of nutrition care by Australian fitness businesses: a website analysis.
AB  - OBJECTIVES: To investigate the intention of fitness businesses to promote the
      provision of nutrition care from personal trainers. STUDY DESIGN: Cross-sectional
      evaluation of webpage content. METHODS: Fitness businesses within two Australian
      federal electorates were identified using the Fitness Australia list of
      registered fitness businesses. Inductive content analysis of these fitness
      business websites and associated social media sites was undertaken to compare
      website content to the Fitness Australia Position Statement outlining the Roles
      and Responsibilities of Registered Fitness Professionals. Fitness businesses were
      classified as 'within scope of practice' if they referred to national nutrition
      guidelines or dietetic services. 'At risk of being beyond scope' included
      websites which did not include enough information to definitively state within or
      beyond scope. Fitness businesses were classified as 'definitely beyond scope of
      practice' if they advertised nutrition care which clearly extended beyond
      translation of the national dietary guidelines. RESULTS: Of the businesses
      reviewed, 15% were within scope despite none referring to a dietitian; 34% were
      at risk of being beyond scope; and 51% were beyond scope as they advertised
      nutrition care such as personalized diets without indicating dietetic input.
      CONCLUSIONS: A considerable portion of fitness businesses reviewed advertised
      their personal trainers as able to provide nutrition care outside the recommended
      scope of practice. Strategies that help fitness businesses and personal trainers
      to support clients to have healthy dietary behaviours without extending outside
      the scope of practice are warranted.

PMID- 27697293
TI  - Enhancing breadth of knowledge within multidisciplinary doctoral research:
      reflections from the Cambridge Generic Nutrition Training course for non
      nutritionist postgraduates and professionals.

PMID- 27697294
TI  - Asymmetric flow field flow fractionation methods for virus purification.
AB  - Detailed biochemical and biophysical characterization of viruses requires viral
      preparations of high quantity and purity. The optimization of virus production
      and purification is an essential, but laborious and time-consuming process.
      Asymmetric flow field flow fractionation (AF4) is an attractive alternative
      method for virus purification because it is a rapid and gentle separation method
      that should preserve viral infectivity. Here we optimized the AF4 conditions to
      be used for purification of a model virus, bacteriophage PRD1, from various types
      of starting materials. Our results show that AF4 is well suited for PRD1
      purification as monitored by virus recovery and specific infectivity. Short
      analysis time and high sample loads enabled us to use AF4 for preparative scale
      purification of PRD1. Furthermore, we show that AF4 enables the rapid real-time
      analysis of progeny virus production in infected cells.

PMID- 27697295
TI  - Information-Based Approaches of Noninvasive Transcranial Brain Stimulation.
AB  - Progress in cognitive neuroscience relies on methodological developments to
      increase the specificity of knowledge obtained regarding brain function. For
      example, in functional neuroimaging the current trend is to study the type of
      information carried by brain regions rather than simply compare activation levels
      induced by task manipulations. In this context noninvasive transcranial brain
      stimulation (NTBS) in the study of cognitive functions may appear coarse and old
      fashioned in its conventional uses. However, in their multitude of parameters,
      and by coupling them with behavioral manipulations, NTBS protocols can reach the
      specificity of imaging techniques. Here we review the different paradigms that
      have aimed to accomplish this in both basic science and clinical settings and
      follow the general philosophy of information-based approaches.

PMID- 27697296
TI  - Internal and external validation of an ESTRO delineation guideline - dependent
      automated segmentation tool for loco-regional radiation therapy of early breast
      cancer.
AB  - BACKGROUND AND PURPOSE: To internally and externally validate an atlas based
      automated segmentation (ABAS) in loco-regional radiation therapy of breast
      cancer. MATERIALS AND METHODS: Structures of 60 patients delineated according to
      the ESTRO consensus guideline were included in four categorized multi-atlas
      libraries using MIM MaestroTM software. These libraries were used for auto
      segmentation in two different patient groups (50 patients from the local
      institution and 40 patients from other institutions). Dice Similarity
      Coefficient, Average Hausdorff Distance, difference in volume and time were
      computed to compare ABAS before and after correction against a gold standard
      manual segmentation (MS). RESULTS: ABAS reduced the time of MS before and after
      correction by 93% and 32%, respectively. ABAS showed high agreement for lung,
      heart, breast and humeral head, moderate agreement for chest wall and axillary
      nodal levels and poor agreement for interpectoral, internal mammary nodal regions
      and LADCA. Correcting ABAS significantly improved all the results. External
      validation of ABAS showed comparable results. CONCLUSIONS: ABAS is a clinically
      useful tool for segmenting structures in breast cancer loco-regional radiation
      therapy in a multi-institutional setting. However, manual correction of some
      structures is important before clinical use. The ABAS is now available for
      routine clinical use in Danish patients.

PMID- 27697297
TI  - Immunohistochemistry of apoptosis-related proteins in retinoblastoma.
AB  - Retinoblastoma is the most common intraocular malignant neoplasia during
      childhood and results from the partial or total inactivity of the retinoblastoma
      protein (pRb). In the absence of pRb, the E2F transcription factors increase the
      levels of cell cycle proteins as well as some pro-apoptotic proteins. We intended
      to study the immunohistochemistry profile of apoptotic-related proteins in
      retinoblastoma. We also evaluated the association between the expression of
      apoptotic protein and stage of tumor or survivor after a 5year follow up.
      Apoptosis-related proteins (Apaf-1, Bak, Bax, Bcl-2, Bcl-xL, Bim-long, MDM2, p53,
      pro-caspase-3, PUMA, Smac/DIABLO and cleaved caspase-3) were evaluated using
      immunohistochemistry on tissue microarrays which contained samples of
      retinoblastoma tumors taken from ninety-three patients without any treatment
      previous to surgery. The immunohistochemistry reactions were evaluated using an
      optical microscope as well as the ACIS III(r) platform. The pro-apoptotic
      proteins (APAF-1, Bax, p53, PUMA, Smac/DIABLO) were more frequently expressed
      than the anti-apoptotic proteins (Bcl-2, Bcl-xL and MDM2). The protein Bcl-xL had
      a negative correlation with cleaved caspase-3, a marker of cell apoptosis. Bcl-xL
      may be implicated in an apoptosis block.

PMID- 27697298
TI  - Mammillary bodies infiltration in Langerhans-cell histiocytosis.

PMID- 27697299
TI  - Transcriptional regulation of inflammasome-associated pattern recognition
      receptors, and the relevance to disease pathogenesis.
AB  - Over the last decade it has emerged that inflammasome complexes provide a pivotal
      platform for the host innate immune system to respond to exogenous infectious
      microbes (viruses, bacteria, fungi) and non-infectious environmental agents
      (cigarette smoke, pollution), as well as endogenous "danger" signals. Upon the
      canonical activation of inflammasomes, a key effector function is to catalyze,
      via caspase-1, the maturation of the potent pro-inflammatory cytokines
      interleukin (IL)-1beta and IL-18, which, in addition to chronic inflammatory
      responses have also been intimately linked to the inflammatory form of lytic cell
      death, pyroptosis. However, recent evidence suggests that inflammasomes exhibit
      marked pleiotropism beyond their canonical functions, whereby their activation
      can also influence a large number of cellular responses including proliferation,
      apoptosis, autophagy and metabolism. It is therefore not surprising that the
      dysregulated expression and/or activation of inflammasomes is increasingly
      implicated in numerous disease states, such as chronic auto-inflammatory and
      autoimmune disorders, metabolic syndrome, neurodegenerative and cardiovascular
      diseases, as well as cancer. In this review we will highlight recent advancements
      in our understanding of the transcriptional regulation of genes encoding
      inflammasome-associated innate immune receptors, and the impact on a variety of
      cellular responses during disease pathogenesis.

PMID- 27697300
TI  - [Massive intraatrial mass?]
AB  - Posterior mediastinal hematoma in a rare and potentially lethal disease and is
      frequently consecutive to a traumatism. We report the original case of a 88-year
      old male admitted to our department for lipothymia and syncope related to a
      severe compression of the left atrium by an important mediastinal hematoma
      mimicking in transthoracic echocardiography an obstructive intraatrial mass.

PMID- 27697301
TI  - [Is there a disassociation of ventilatory and electromyographic thresholds in
      patients with heart disease during a graded cycling exercise?]
AB  - : Exercise prescription was generally based on the determination of ventilatory
      thresholds (VT1, VT2) during cardiopulmonary exercise testing (CPX). Changes in
      surface electromyographic activity (EMGth1, EMGth2) were also related to VT1 and
      VT2 in healthy subjects. OBJECTIVE: To observe the occurrence of EMGth1 and
      EMGth2 and whether these events accompany VT1 and VT2 during CPX in cardiac
      patients (CP). METHOD: Thirty-four CP (62.1+/-7.3years, 172.1+/-6.3cm, 81.3+/
      15.3kg, BMI: 27.3+/-4.1) performed a cycle CPX at a 60-rpm cadence. VT1 was
      determined as the breakpoint in the curve of carbon dioxide output against oxygen
      uptake plot (V-slope method). VT2 was defined as the point at which the ratio of
      minute ventilation to carbon dioxide output starts to increase. The root mean
      square of electromyogram (rms-EMG) was on-line calculated from the real time
      bipolar surface electromyographic signals recorded from the vastus lateralis.
      EMGth1 and EMGth2 were defined as the first and the second breakpoints in the rms
      EMG-power output relationship. RESULTS: Peak values of oxygen uptake (16.3+/
      4.6mL.min-1.kg-1) and heart rate (106.7+/-13.8bpm) were reached at 112.9+/-38.5w
      (PMT). VT1 and VT2 occurred at 71.1+/-25.9w (62.5+/-5.5% PMT) and 87.9+/-28.6w
      (78.0+/-5.1% PMT). All subjects presented two breakpoints in the rms-EMG curve,
      EMGth1 at 68.0+/-24.7w and EMGth2 at 88.5+/-30.1w, i.e. 60.0+/-7.6 and 78.6+/
      5.0% of PMT. EMGth1 occurred significantly before VT1 (P=0.004, small effect
      size). No significant difference was observed between EMGth2 and VT2 (P=0.13,
      small effect size). CONCLUSION: The EMGth1 occurrence before VT1 suggested a role
      of skeletal muscle conditioning on ventilatory responses, which should be taken
      into account in cardiac rehabilitation program prescription.

PMID- 27697303
TI  - Existing equations to estimate lean body mass are not accurate in the critically
      ill: Results of a multicenter observational study.
AB  - BACKGROUND & AIMS: Lean body mass (LBM), quantified using computed tomography
      (CT), is a significant predictor of clinical outcomes in the critically ill.
      While CT analysis is precise and accurate in measuring body composition, it may
      not be practical or readily accessible to all patients in the intensive care unit
      (ICU). Here, we assessed the agreement between LBM measured by CT and four
      previously developed equations that predict LBM using variables (i.e. age, sex,
      weight, height) commonly recorded in the ICU. METHODS: LBM was calculated in 327
      critically ill adults using CT scans, taken at ICU admission, and 4 predictive
      equations (E1-4) that were derived from non-critically adults since there are no
      ICU-specific equations. Agreement was assessed using paired t-tests, Pearson's
      correlation coefficients and Bland-Altman plots. RESULTS: Median LBM calculated
      by CT was 45 kg (IQR 37-53 kg) and was significantly different (p < 0.001) from
      E1 (52.5 kg; IQR: 42-61 kg), E2 (55 kg; IQR 45-64 kg), E3 (55 kg; IQR 44-64 kg),
      and E4 (54 kg; IQR 49-61 kg). Pearson correlation coefficients suggested moderate
      correlation (r = 0.739, 0.756, 0.732, and 0.680, p < 0.001, respectively). Each
      of the equations overestimated LBM (error ranged from 7.5 to 9.9 kg), compared
      with LBM calculated by CT, suggesting insufficient agreement. CONCLUSIONS: Our
      data indicates a large bias is present between the calculation of LBM by CT
      imaging and the predictive equations that have been compared here. This
      underscores the need for future research toward the development of ICU-specific
      equations that reliably estimate LBM in a practical and cost-effective manner.

PMID- 27697302
TI  - A phase 1, randomized, controlled dose-escalation study of EP-1300 polyepitope
      DNA vaccine against Plasmodium falciparum malaria administered via
      electroporation.
AB  - : Plasmodium falciparum malaria is one of the leading infectious causes of
      childhood mortality in Africa. EP-1300 is a polyepitope plasmid DNA vaccine
      expressing 38 cytotoxic T cell epitopes and 16 helper T cell epitopes derived
      from P. falciparum antigens expressed predominantly in the liver phase of the
      parasite's life cycle. We performed a phase 1 randomized, placebo-controlled,
      dose escalation clinical trial of the EP-1300 DNA vaccine administered via
      electroporation using the TriGrid Delivery System device (Ichor Medical Systems).
      Although the delivery of the EP-1300 DNA vaccine via electroporation was safe,
      tolerability was less than that usually observed with standard needle and syringe
      intramuscular administration. This was primarily due to acute local discomfort at
      the administration site during electroporation. Despite the use of
      electroporation, the vaccine was poorly immunogenic. The reasons for the poor
      immunogenicity of this polyepitope DNA vaccine remain uncertain. CLINICAL TRIALS
      REGISTRATION: ClinicalTrials.gov NCT01169077.

PMID- 27697304
TI  - Neurodevelopmental outcome of term infants with perinatal asphyxia with hypoxic
      ischemic encephalopathy stage II.
AB  - BACKGROUND: Perinatal asphyxia with hypoxic ischemic encephalopathy (HIE) causes
      significant mortality and morbidity in developing countries. There is limited
      information about long term neurodevelopmental outcome of infants with neonatal
      encephalopathy. METHODS: Term infants with the diagnosis of perinatal asphyxia
      were followed up in neurodevelopmental clinics of Manipal Teaching hospital,
      Nepal. Study design was prospective mixed longitudinal study. Prematurity, major
      congenital malformations, other intracranial pathology, birth weight <2500g and
      chromosomal abnormalities were excluded. After consent and enrollment their
      detailed perinatal history, Apgar score, resuscitation measures and outcome
      parameters were recorded on a predesigned proforma. Developmental assessment was
      done with Denver Developmental Screening Tool 2nd edition (DDST 2) at the age of
      3months, 6months, 9months, 1year, 18months and 2years. RESULTS: Total 187
      assessments done in the age group of 3months to 2years among HIE stage 2
      patients. Impaired hearing and vision was noted in 5.3% while language delay was
      observed in 19.2% of infants. Abnormal tone and deep tendon reflexes were noted
      in 46.2% infants at 3months. Abnormal tone and reflexes were noted only in 18.8%
      and 9.4% respectively at the age of 2years. Overall, gross motor delay was noted
      in 55(29.4%) of patient, 34(18.2%) showed fine motor delay and 17.1% social
      delay. Seizures were persistent in 15.6% patients at 2years age. CONCLUSION:
      Infants affected with HIE have delay in all sectors of developmental milestones.
      Motor abnormalities are common and tend to improve with advancing age.

PMID- 27697305
TI  - Early cardiac involvement in an infantile Sandhoff disease case with novel
      mutations.
AB  - INTRODUCTION: Hepatosplenomegaly is often present in infantile Sanshoff disease.
      However, cardiac involvement is extremely uncommon. CASE REPORT: We describe a 14
      month-old female baby who exhibited mitral regurgitation and cardiomegaly at the
      age of 2months, dilation of the left atrium and left ventricle at age of 6months,
      followed by regression of developmental milestones after an episode of minor
      infection at age of 14months. Brain magnetic resonance imaging revealed signal
      changes over the bilateral thalami, bilateral cerebral white matter and left
      putamen. An examination of the fundus showed presence of cherry-red spots in both
      macular areas. The lysosomal enzymatic activities showed a marked reduction of
      beta-hexosaminidase B (HEXB) activity. Two novel mutations of HEXB gene were
      identified. One of the mutations was a c.1538 T>C mutation, which predicted a
      p.L513P amino acid substitution of leucine to proline; the other was a c.299+5
      G>A mutation, which was a splice site mutation. CONCLUSION: Cardiac involvement
      might occur prior to neurological symptoms in infantile Sandhoff disease, and it
      should be included in the differential diagnoses of metabolic cardiomyopathies in
      the infantile stage.

PMID- 27697306
TI  - The relationship between motor proficiency and mental health outcomes in young
      adults: A test of the Environmental Stress Hypothesis.
AB  - Growing evidence has highlighted the importance of motor proficiency in relation
      to psychosocial outcomes including self-perceived competence in various domains,
      perceived social support, and emotional areas such as anxiety and depression. The
      Environmental Stress Hypothesis-elaborated (Cairney, Rigoli, & Piek, 2013) is a
      proposed theoretical framework for understanding these relationships and recent
      studies have begun examining parts of this model using child and adolescent
      populations. However, the extent to which the relationships between these areas
      exist, persist or change during early adulthood is currently unclear. The current
      study aimed to investigate the Environmental Stress Hypothesis in a sample of 95
      young adults aged 18-30years and examined the mediating role of physical self
      worth and perceived social support in the relationship between motor proficiency
      and internalising symptoms. The McCarron Assessment of Neuromuscular Development
      (McCarron, 1997) was used to assess motor proficiency, the Depression Anxiety
      Stress Scale (Lovibond & Lovibond, 1995) provided a measure of internalising
      symptoms, and the Physical Self Perceptions Profile (Fox & Corbin, 1989) and the
      Multidimensional Scale of Perceived Social Support (Zimet, Dahlem, Zimet, &
      Farley, 1988) were used to investigate the possible mediating role of physical
      self-worth and perceived social support respectively. Potential confounding
      variables such as age, gender and BMI were also considered in the analysis.
      Structural Equation Modelling revealed that perceived social support mediated the
      relationship between motor proficiency and internalising symptoms, whereas, the
      mediating role of physical self-worth was non-significant. The current results
      provide support for part of the model pathways as described in the Environmental
      Stress Hypothesis and suggest an important relationship between motor proficiency
      and psychosocial outcomes in young adults. Specifically, the results support
      previous literature regarding the significant role of perceived social support
      for mental well-being and suggest that an intervention that considers social
      support may also indirectly influence mental health outcomes in young adults who
      experience movement difficulties.

PMID- 27697307
TI  - Bioresorbable scaffold adjustment in an ostial lesion with the Szabo technique.

PMID- 27697309
TI  - Recurrence factors and prevention of complications of pediatric differentiated
      thyroid cancer.
AB  - BACKGROUND/OBJECTIVE: To investigate the factors associated with recurrence of
      differentiated thyroid cancer in children. We combined the clinical and
      pathological features to guide surgical treatment options, ensure efficacy, and
      reduce complications. METHODS: A prospective analysis of clinical data of 43
      cases of pediatric differentiated thyroid cancer from March 2008 to June 2014
      admitted in our department, including 38 cases of papillary cancers and five
      cases of follicular cancer; 40 cases were Stage I and three cases were Stage II
      (Union for International Cancer Control [UICC] Tumor Node Metastasis
      classification [TNM] staging). We performed the operations according to the
      condition of lesions and lymph nodes. Operations included subtotal resection in
      36 cases, total resection in seven cases. We applied statistical methods to
      investigate the risk factors of recurrence and postoperative complications.
      RESULTS: The pathologic lymph node metastasis rate was 67.44% (29/43): Area VI
      lymph nodes metastases in 20 cases and Area III/IV or Area II/V lymph nodes
      metastases in nine cases. Postoperative hypocalcemia symptoms were seen in three
      cases and hoarseness in three cases, for a total rate of 13.95% (6/43). Until
      December 2015, patients were followed up from 1.5 years to 8.7 years, with a
      median of 4.9 years. There were three cases of cervical lymph node recurrence,
      one case of local recurrence, and one case of lung metastasis, for a total
      recurrence rate of 11.63% (5/43); all patients survived. Log-rank test of Kaplan
      Meier curves and Cox stepwise regression analysis showed that lesion number,
      extrathyroidal extension, and lymph nodes metastases were the risk factors for
      postoperative recurrence; the relative risk values were, respectively, 3.117,
      2.816, and 4.628 (p=0.041, p=0.048, and p=0.031, respectively) and the 95%
      confidence intervals (CI) were, respectively, 1.094~8.735, 1.046~7.932, and
      1.189~10.205. However, the lesion excision approach was not a risk factor for
      postoperative recurrence (p=0.107). The logistic stepwise regression model showed
      that lesion excision approach was a risk factor for postoperative hypocalcemia
      and hoarseness; the odds ratio value was 2.537 (p=0.037) and the 95% CI was
      1.034~6.983. CONCLUSION: Pediatric differentiated thyroid cancer has a high
      metastatic rate to lymph nodes and distant organs, but the total prognosis is
      good. Application of total resection cannot necessarily reduce the relapse rate
      of pediatric differentiated thyroid cancer, but it may increase the postoperative
      hypocalcemia and hoarseness. The authors propose strictly adhering to various
      operation indicators, and carrying out various operations with a full
      understanding of the local lesion and lymph nodes in order to reduce relapse and
      postoperative complications.

PMID- 27697308
TI  - Calcific aortic stenosis and its correlation with a novel inflammatory marker,
      the lymphocyte/monocyte ratio.
AB  - INTRODUCTION: Calcific aortic valve disease, a chronic progressive disorder, is
      the leading cause of valve replacement among elderly patients. The
      lymphocyte/monocyte ratio has been recently put forward as an inflammatory marker
      of relevance in several cancers as well as in cardiovascular disease. This study
      aims to assess the correlation between severity of calcific aortic stenosis and
      the lymphocyte/monocyte ratio. METHODS: The study retrospectively included 178
      patients with a diagnosis of calcific aortic stenosis and 139 age- and gender
      matched controls. The patients were divided into two groups according to the
      severity of aortic stenosis: mild-to-moderate and severe. RESULTS: An inverse
      correlation was discerned between the severity of the aortic stenosis process
      (mean gradient) and the lymphocyte/monocyte ratio (r=-0.232, p=0.002). The
      lymphocyte/monocyte ratio was observed to decrease as the severity of aortic
      stenosis increased (p<0.001) in the group with severe aortic stenosis compared
      with the mild-to-moderate aortic stenosis and control groups (p<0.001, p=0.005
      respectively), and in the group with mild-to-moderate aortic stenosis compared
      with the control group (p=0.003). Multivariate regression analysis revealed that
      the lymphocyte/monocyte ratio was independently related to the severity of
      calcific aortic stenosis (p=0.003). CONCLUSION: The present study demonstrated
      the existence of a statistically significant inverse relationship between
      severity of calcific aortic stenosis and the lymphocyte/monocyte ratio. The study
      also revealed that the lymphocyte/monocyte ratio was significantly related to the
      severity of the aortic valve stenosis process.

PMID- 27697310
TI  - Comprehensive study on the effects of sodium and potassium additives in size
      exclusion chromatographic separations of protein biopharmaceuticals.
AB  - To separate proteins solely based on their difference in hydrodynamic volume in
      size exclusion chromatography (SEC), the ionic strength of the mobile phase has
      to be increased in order to avoid secondary ionic interactions between proteins
      and the stationary phase. However, adding salts to the mobile phase can have a
      serious effect on protein aggregation and can lead to artifacts. In the present
      study, several monoclonal antibodies (mAbs) and the antibody-drug conjugate
      (ADC), trastuzumab emtansine were selected to study the effect of mobile phase
      salt additive on aggregation measurements. In a first instance, the same
      aggregation ratios between the dimeric and monomeric forms of ten mAbs approved
      by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA)
      were obtained with three UHP-SEC columns. However, SEC analysis using various
      amounts of NaCl provided surprising results for rituximab, e.g. presence of 0.8%
      aggregates with a mobile phase containing 0.2M NaCl, while no aggregates were
      observed without NaCl in the mobile phase. Despite the absence of monomeric
      protein adsorption at the surface of the SEC resin, the comparison of sodium- and
      potassium-based salts demonstrated the superiority of potassium-based salts to
      reduce possible secondary electrostatic interactions, mainly between protein
      dimers and the SEC support as well as to lower protein-salts interaction. To
      investigate the effect of mobile phase salt additives on SEC measurements,
      fluorescence spectroscopy provided insights related to the possible contribution
      of protein tertiary structure. Indeed, biopharmaceuticals could be classified
      depending on the exposure of their tryptophan residues to the solvent in order to
      understand their propensity to interact with the stationary phase or/and to
      undergo self-association.

PMID- 27697311
TI  - Axenfeld-Rieger Syndrome and Leukoencephalopathy Caused by a Mutation in FOXC1.

PMID- 27697312
TI  - Myopathy in Childhood Muscle-Specific Kinase Myasthenia Gravis.
AB  - BACKGROUND: Adult and pediatric patients suffering from MuSK (muscle-specific
      kinase) -antibody positive myasthenia gravis exhibit similar features to
      individuals with acetylcholine receptor (AChR) antibodies, but they differ in
      several characteristics such as a predominant bulbar, respiratory and neck
      weakness, a generally worse disease severity and a tendency to develop muscle
      atrophy. Muscle atrophy is a rare phenomenon that is usually restricted to the
      facial muscles. RESULTS: We describe a girl with MuSK-antibody positive
      myasthenia gravis who developed a myopathy with severe generalized muscular
      weakness, muscle atrophy, and myopathic changes on electromyography. CONCLUSION:
      This is the first published example of a generalized myopathic syndrome in
      myasthenia gravis. We review the relevant literature and discuss the hypothesis
      of a mitochondrial myopathy as a pathogenic mechanism in MuSK-antibody positive
      myasthenia gravis.

PMID- 27697313
TI  - Treatment of Neurogenetic Developmental Conditions: From 2016 into the Future.
AB  - BACKGROUND: Neurogenetic developmental conditions represent a heterogeneous group
      of rare inherited disorders with neurological manifestation during development.
      Treatments for these conditions have largely been supportive; however, a number
      of treatments are emerging which target the underlying physiology and offer great
      potential. Our aim was to present a state-of-the-art overview of the current and
      potential causal treatments available or under development for neurogenetic
      developmental conditions. METHODS: In this review, we focus on the following
      neurogenetic developmental conditions: (1) inborn errors of metabolism causing
      neurogenetic developmental conditions, (2) fragile X syndrome, (3) Rett syndrome,
      (4) tuberous sclerosis complex, 5) Down syndrome and other neurogenetic
      developmental conditions. RESULTS: A large group of inborn errors of metabolism
      leads to neurodevelopmental disability, affecting the central nervous system
      during infancy or childhood and can present with comorbidities such as
      intellectual developmental disability, epilepsy, atypical cerebral palsy, autism
      spectrum disorder, behavioral and psychiatric disturbances, for which causal
      treatments are discussed. CONCLUSIONS: The advent of these new disease-modifying
      therapies has the potential to reverse the underlying neural mechanisms of these
      debilitating conditions, which may provide prospect to affected individuals.

PMID- 27697314
TI  - An Emerging Adverse Outcome of Therapeutic Hypothermia in Neonates.

PMID- 27697315
TI  - Comparison of short-term clinical outcomes between transanal and laparoscopic
      total mesorectal excision for the treatment of mid and low rectal cancer: A meta
      analysis.
AB  - AIM: The objective of this meta-analysis was to evaluate the feasibility, safety,
      and short-term clinical outcomes of transanal total mesorectal excision (TaTME)
      comparing with laparoscopy total mesorectal excision (LapTME) for mid and low
      rectal cancer. METHODS: Relevant studies were searched from the databases of
      Pubmed, Embase, and the Cochrane Library. The qualities of all of the included
      studies were evaluated using Newcastle-Ottawa Scale (NOS). The synthesized
      outcomes were pooled using fixed-effects models or random-effects models, which
      weighted the odds ratio (OR) or mean difference (MD) with 95% confidence
      intervals (95% CI). A funnel plot was used to evaluate the publication bias.
      RESULTS: Seven original studies including 209 TaTME patients and 257 LapTME
      patients with rectal cancer met the inclusion criteria in this meta-analysis.
      Compared with LapTME, TaTME showed a longer CRM, lower rate of positive CRM,
      complete TME rate, and less operative time. There were no significant differences
      in the outcomes of the harvested lymph nodes, distal margin distance, hospital
      stay, intraoperative complications, anastomotic leakage, postoperative
      complications, reoperation, readmission, or conversion between the TaTME group
      and the LapTME group. CONCLUSIONS: Compared with LapTME, TaTME is a feasible and
      safe approach for patients with mid and low rectal cancer. In addition, TaTME
      showed a better short-term clinical outcomes, such as a longer CRM, lower risk of
      positive CRM, higher complete quality of TME rate, and shorter operative
      duration. Further prospective studies with long-term follow-up are required.

PMID- 27697316
TI  - Time-driven activity-based costing to identify opportunities for cost reduction
      in pediatric appendectomy.
AB  - PURPOSE: As reimbursement programs shift to value-based payment models
      emphasizing quality and efficient healthcare delivery, there exists a need to
      better understand process management to unearth true costs of patient care. We
      sought to identify cost-reduction opportunities in simple appendicitis management
      by applying a time-driven activity-based costing (TDABC) methodology to this high
      volume surgical condition. METHODS: Process maps were created using medical
      record time stamps. Labor capacity cost rates were calculated using national
      median physician salaries, weighted nurse-patient ratios, and hospital cost data.
      Consumable costs for supplies, pharmacy, laboratory, and food were derived from
      the hospital general ledger. RESULTS: Time-driven activity-based costing resulted
      in precise per-minute calculation of personnel costs. Highest costs were in the
      operating room ($747.07), hospital floor ($388.20), and emergency department
      ($296.21). Major contributors to length of stay were emergency department
      evaluation (270min), operating room availability (395min), and post-operative
      monitoring (1128min). The TDABC model led to $1712.16 in personnel costs and
      $1041.23 in consumable costs for a total appendicitis cost of $2753.39.
      CONCLUSION: Inefficiencies in healthcare delivery can be identified through
      TDABC. Triage-based standing delegation orders, advanced practice providers, and
      same day discharge protocols are proposed cost-reducing interventions to optimize
      value-based care for simple appendicitis. LEVEL OF EVIDENCE: II.

PMID- 27697317
TI  - The effectiveness of costal cartilage excision in children for slipping rib
      syndrome.
AB  - PURPOSE: Slipping rib syndrome (SRS) is an elusive diagnosis. Previous reports
      have been single cases or small series. We previously reported a small
      multicenter review with encouraging early results. We now describe our matured
      experience. METHODS: This is a follow-up study of patients with SRS from 2006 to
      2015. Included are 5 previously analyzed patients and 25 new patients. Patients
      were called to review current symptoms, course, and satisfaction. RESULTS: From
      2006 to 2015, 30 patients underwent 38 operations. Eight underwent re-operation.
      All had reproducible pain localized to the costal margin, 60% had a popping
      sensation, and 23% were bilateral. 86% were female. Median age of symptom onset
      was 14 (IQR 13.75-15) years, while median age at diagnosis was 16 (IQR 15-17).
      Contact was possible with 18/30 patients, and mean follow up time was 1.3years.
      72% of those felt they were cured, and 44% rated satisfaction a 10/10 (mean
      7.84). Of those not cured, all reported significant improvement. CONCLUSIONS:
      Costal cartilage excision is an effective treatment for SRS and should be
      considered early in the workup of costal margin pain in a normally active
      population. Case Series with no Comparison Group - Level IV.

PMID- 27697318
TI  - Surgical strategy according to the anatomical types of congenital portosystemic
      shunts in children.
AB  - BACKGROUND: Congenital portosystemic shunts (CPSS) with intrahepatic portal vein
      (IHPV) hypoplasia or absence cause encephalopathy or pulmonary hypertension (PH).
      Acute shunt closure may result in postoperative portal hypertension. The aim of
      this study was to propose a surgical strategy according to the anatomical types
      of CPSS and IHPV. METHODS: Twenty-three CPSS patients were diagnosed from1990 to
      2015. All patients were evaluated by computed tomography, angiography, and PV
      pressure monitoring under a shunt occlusion test. CPSS were categorized into 5
      types according to the anatomical shunt location. RESULTS: The median age at
      diagnosis was 34months. Three of 23 total patients, who had an extrahepatic
      portosystemic shunt with a hypoplastic IHPV, died before treatment initiation
      because of severe PH. Fourteen cases received surgical or interventional
      treatment at the median age of 5years. A total of 6 cases received surgical
      therapy, including liver transplants for 2 absent IHPV cases. The remaining 8
      cases received interventional coiling. All shunt ligations were successfully
      accomplished in 1-stage ligation without any complications. After the treatment,
      the hypoplastic IHPV gradually enlarged with an efficient portal inflow.
      CONCLUSION: A precise pretreatment anatomical evaluation of CPSS and IHPV types
      is mandatory for the selection of surgical treatment. LEVEL OF EVIDENCE:
      Diagnostic study - level II and treatment study - level III.

PMID- 27697320
TI  - Is climate change an unforeseen, irresistible and external factor - A force
      majeure in marine environmental law?
AB  - Several environmental laws include provisions on natural causes or force majeure,
      which except States from their commitments if it can be proven that the failure
      to meet the commitment is due to factors outside their control. The European
      Union Marine Strategy Framework Directive (MSFD) has a pivotal role in managing
      EU marine waters. This paper analyses natural causes and force majeure provisions
      of the MFSD and other marine legislation, and addresses their interaction with
      climate change and its consequences, especially the effect on the obligation of
      ensuring seas are in Good Environmental Status. Climate change is an exogenic
      unmanaged pressure in that it emanates from outside the area being managed but in
      which the management authority has to respond to the consequences of climate
      change, such as sea level rise and temperature elevation, rather than its causes.
      It is suggested that a defence by a Member State of force majeure may be accepted
      if an event was proven to be due to an externality of control, irresistible and
      unforeseeable. The analysis contends that countering such a legal defence would
      centre on the fact that climate change is a well-accepted phenomenon, is foreseen
      with an accepted level of confidence and probability and is due to human actions.
      However, as yet, this has not been legally tested.

PMID- 27697319
TI  - Benthic foraminifera as bio-indicators of chemical and physical stressors in
      Hammerfest harbor (Northern Norway).
AB  - We investigated benthic foraminiferal assemblages in contaminated sediments in a
      subarctic harbor of Northern Norway to assess their utility as indicators of
      anthropogenic impacts. Sediments in the harbor are repositories for POPs and
      heavy metals supplied through discharges from industry and shipping activities.
      Sediment contaminant concentrations are at moderate to poor ecological quality
      status (EcoQS) levels. The EcoQS based on benthic foraminiferal diversity
      reflects a similar trend to the EcoQS based on contaminant concentrations.
      Foraminiferal density and diversity is low throughout the harbor with distinct
      assemblages reflecting influence of physical disturbances or chemical stressors.
      Assemblages impacted by physical disturbance are dominated by L. lobatula and E.
      excavatum, while assemblages impacted by chemical stressors are dominated by
      opportunistic species S. fusiformis, S. biformis, B. spathulata and E. excavatum.
      The foraminiferal assemblage from an un-impacted nearby fjord consists mainly of
      agglutinated taxa. These assemblages provides a valuable baseline of the
      ecological impacts of industrialization in northern coastal communities.

PMID- 27697321
TI  - Biological effects of gold mine tailings on the intertidal marine environment in
      Nova Scotia, Canada.
AB  - From 1861 to the 1940s, gold was produced from 64 mining districts in Nova
      Scotia, where mercury amalgamation was the dominant method for the extraction of
      gold from ore until the 1880s. As a result, wastes (tailings) from the milling
      process were contaminated by mercury and were high in naturally occurring
      arsenic. In 2004 and 2005, sediments, water and mollusc tissues were collected
      from 29 sampling stations at nine former gold mining areas along the Atlantic
      coastline and were analysed for arsenic and mercury. The resulting data were
      compared with environmental quality guidelines. Samples indicated high potential
      risk of adverse effects in the intertidal environments of Seal Harbour, Wine
      Harbour and Harrigan Cove. Arsenic in Seal Harbour was bioavailable, resulting in
      high concentrations of arsenic in soft-shell clam tissues. Mercury concentrations
      in tissues were below guidelines. This paper presents results of the sampling
      programs and implications of these findings.

PMID- 27697322
TI  - Capability of Paraguacu estuary (Todos os Santos Bay, Brazil) to form oil-SPM
      aggregates (OSA) and their ecotoxicological effects on pelagic and benthic
      organisms.
AB  - For experiments concerning the formation of oil-suspended particulate matter
      (SPM) aggregates (OSA), oil and sediment samples were collected from Campos Basin
      and six stations of Paraguacu estuary, Todos os Santos Bay, Brazil, respectively.
      The sediments samples were analyzed for organic matter determined by the EMBRAPA
      method, nitrogen determined by the Kjeldahl method, and phosphorus determined by
      the method described by Aspila. The oil trapped in OSA was extracted following
      the method described by Moreira. The experiment showed a relationship between the
      amount of organic matter and OSA formation and consequently the dispersion of the
      studied oil. On the basis of the buoyancy of OSA and the ecotoxicological effects
      on pelagic and benthic community, the priority areas for application of
      remediation techniques are Cachoeira, Maragogipe, and Salinas da Margarida
      because of the large amount of oil that accumulated at the bottom of the
      experiment flask (5.85%, 27.95%, and 38,98%; 4.2%, 17.66%, and 32.64%; and
      11.82%, 8.07%, and 10.91% respectively).

PMID- 27697323
TI  - Orbital abscess that masqueraded as a retrobulbar haemorrhage.

PMID- 27697324
TI  - Angioid Streaks in the Fundus of a 13-Year-Old Girl.

PMID- 27697325
TI  - Identifying Depression in Neonatal Intensive Care Unit Parents: Then What?

PMID- 27697326
TI  - Behavioral Problems and Childhood Epilepsy: Parent vs Child Perspectives.
AB  - OBJECTIVE: To test whether the reported association between pediatric epilepsy
      and behavioral problems may be distorted by the use of parental proxy report
      instruments. STUDY DESIGN: Children in the Connecticut Study of Epilepsy were
      assessed 8-9 years after their epilepsy diagnosis (time-1) with the parent-proxy
      Child Behavior Check List (CBCL) (ages 6-18 years) or the Young Adult Self-Report
      (>=18 years of age). For children <18 years of age, parents also completed the
      Child Health Questionnaire, which contains scales for impact of child's illness
      on the parents. The same study subjects completed the Adult Self-Report 6-8 years
      later (time-2). Sibling controls were also tested. Case-control differences were
      examined for evidence suggesting more behavioral problems in cases with epilepsy
      than in controls based on proxy- vs self-report measures. RESULTS: At time-1,
      parent-proxy CBCL scores were significantly higher (worse) for cases than
      controls (n = 140 matched pairs). After adjustment for Child Health Questionnaire
      scales reflecting parent emotional and time impact, only 1 case-control
      difference on the CBCL remained significant. Self-reported Young Adult Self
      Report scores did not differ between cases and controls (n = 42 pairs). At time
      2, there were no significant self-reported case-control differences on the Adult
      Self-Report (n = 105 pairs). CONCLUSIONS: Parent-proxy behavior measures appear
      to be influenced by the emotional impact of epilepsy on parents. This may
      contribute to apparent associations between behavioral problems and childhood
      epilepsy. Self-report measures in older adolescents (>18 years of age) and young
      adults do not confirm parental perceptions. Evidence suggesting more behavioral
      problems in children with epilepsy should be interpreted in light of the source
      of information.

PMID- 27697328
TI  - Distal Clavicular Torus Fracture in a 15-Year-Old Snowboarder.

PMID- 27697327
TI  - The Benefit of Sleeve Gastrectomy in Obese Adolescents on Nonalcoholic
      Steatohepatitis and Hepatic Fibrosis.
AB  - OBJECTIVE: To determine whether bariatric surgery is effective for the treatment
      of nonalcoholic steatohepatitis (NASH) in adolescence, we compared the efficacy
      of laparoscopic sleeve gastrectomy (LSG) with that of lifestyle intervention
      (nonsurgical weight loss [NSWL]) for NASH reversal in obese adolescents. STUDY
      DESIGN: Obese (body mass index >= 35 kg/m2) adolescents (13-17 years of age) with
      biopsy-proven NAFLD underwent LSG, lifestyle intervention plus intragastric
      weight loss devices (IGWLD), or only NSWL. At baseline and 1 year after
      treatment, patients underwent clinical and psychosocial evaluation, blood tests,
      liver biopsy, polysomnography, and 24-hour ambulatory blood pressure estimation.
      RESULTS: Twenty patients (21%) underwent LSG, 20 (21%) underwent IGWLD, and 53
      (58%) received lifestyle intervention alone (NSWL). One year after treatment,
      patients who underwent LSG lost 21.5% of their baseline body weight, whereas
      patients who underwent IGWLD lost 3.4%, and patients who underwent NSWL increase
      1.7%. In patients who underwent LSG, NASH reverted completely in all patients and
      hepatic fibrosis stage 2 disappeared in 18 patients (90%). After IGWLD, NASH
      reverted in 6 patients (24%) and fibrosis in 7 (37%). Patients who received the
      NSWL intervention did not improve significantly. Hypertension resolved in all
      patients who underwent LSG with preoperative hypertension (12/12) versus 50%
      (4/8) of the patients who underwent IGWLD (P = .02). The cohort-specific changes
      in impaired glucose metabolism were similar: 100% (9/9) of affected patients who
      underwent LSG versus 50% (1/2) of patients who underwent IGWLD (P = .02). LSG was
      also more affective in resolving dyslipidemia (55% [7/12] vs 26% [10/19]; P =
      .05) and sleep apnea (78% [2/9] vs 30% [11/20]; P = .001). CONCLUSION: LSG was
      more effective than lifestyle intervention, even when combined with intragastric
      devices, for reducing NASH and liver fibrosis in obese adolescents after 1 year
      of treatment.

PMID- 27697329
TI  - Childhood Bullous Pemphigoid: A Treatment Challenge.

PMID- 27697330
TI  - Effect of Nutritional Supplementation on Growth in Short and Lean Prepubertal
      Children after 1 Year of Intervention.
AB  - OBJECTIVE: To determine the 1-year effectiveness and safety of nutritional
      supplementation with the study formula on linear growth and weight gain in short
      and lean prepubertal children and to validate the previously reported findings in
      those initially treated with placebo. STUDY DESIGN: Two-phase 1-year intervention
      (double-blind placebo-controlled [0-6 months] and open-labeled extension [6-12
      months]) in which all participants were offered to continue the study using the
      study formula. Anthropometric measures and 3-day food diary were assessed at
      baseline and after 6 and 12 months of intervention. RESULTS: A total of 129 out
      of 150 children (86%) completed the open-labeled extension-phase. In "good"
      consumers of the formula (intake >=50% of recommended dose) throughout the entire
      year height-SDS continued to improve in the extension phase, with a total gain of
      0.19 +/- 0.14 SD. In "good" consumers of the formula initially randomized to the
      placebo-group, the gain in height-SDS significantly improved (from 0.04 +/- 0.13
      to 0.12 +/- 0.11; P = .001), replicating the results of the "good" consumers of
      the formula during the blinded-phase (0.12 +/- 0.12). "Poor" consumers (intake
      <50% of recommended dose) did not improve their height-SDS. No significant
      changes in body mass index SDS were observed with the consumption of the formula.
      A dose-response was found between the amount of formula consumed/kg and the
      increment in height-SDS and weight-SDS (r = 0.36; P < .001 and r = 0.18; P =
      .041, respectively). No serious adverse events were reported. CONCLUSIONS: One
      year of a nutritional supplement was effective in promoting the linear growth of
      short and lean prepubertal children, with no change in body mass index status.
      TRIAL REGISTRATION: ClinicalTrials.gov:NCT01158352.

PMID- 27697331
TI  - Variation in Utilization and Need for Tympanostomy Tubes across England and New
      England.
AB  - OBJECTIVES: To compare rates of typmanostomy tube insertions for otitis media
      with effusion with estimates of need in 2 countries. STUDY DESIGN: This cross
      sectional analysis used all-payer claims to calculate rates of tympanostomy tube
      insertions for insured children ages 2-8 years (2007-2010) across pediatric
      surgical areas (PSA) for Northern New England (NNE; Maine, Vermont, and New
      Hampshire) and the English National Health Service Primary Care Trusts (PCT).
      Rates were compared with expected rates estimated using a Monte Carlo simulation
      model that integrates clinical guidelines and published probabilities of the
      incidence and course of otitis media with effusion. RESULTS: Observed rates of
      tympanostomy tube placement varied >30-fold across English PCT (N = 150) and >3
      fold across NNE PSA (N = 30). At a 25 dB hearing threshold, the overall
      difference in observed to expected tympanostomy tubes provided was -3.41 per 1000
      child-years in England and -0.01 per 1000 child-years in NNE. Observed incidence
      of insertion was less than expected in 143 of 151 PCT, and was higher than
      expected in one-half of the PSA. Using a 20 dB hearing threshold, there were
      fewer tube insertions than expected in all but 2 England and 7 NNE areas. There
      was an inverse relationship between estimated need and observed tube insertion
      rates. CONCLUSIONS: Regional variations in observed tympanostomy tube insertion
      rates are unlikely to be due to differences in need and suggest overall underuse
      in England and both overuse and underuse in NNE.

PMID- 27697332
TI  - Strength, toughness and aging stability of highly-translucent Y-TZP ceramics for
      dental restorations.
AB  - OBJECTIVE: The aim was to evaluate the optical properties, mechanical properties
      and aging stability of yttria-stabilized zirconia with different compositions,
      highlighting the influence of the alumina addition, Y2O3 content and La2O3 doping
      on the translucency. METHODS: Five different Y-TZP zirconia powders (3
      commercially available and 2 experimentally modified) were sintered under the
      same conditions and characterized by X-ray diffraction with Rietveld analysis and
      scanning electron microscopy (SEM). Translucency (n=6/group) was measured with a
      color meter, allowing to calculate the translucency parameter (TP) and the
      contrast ratio (CR). Mechanical properties were appraised with four-point bending
      strength (n=10), single edge V-notched beam (SEVNB) fracture toughness (n=8) and
      Vickers hardness (n=10). The aging stability was evaluated by measuring the
      tetragonal to monoclinic transformation (n=3) after accelerated hydrothermal
      aging in steam at 134 degrees C, and the transformation curves were fitted by the
      Mehl-Avrami-Johnson (MAJ) equation. Data were analyzed by one-way ANOVA, followed
      by Tukey's HSD test (alpha=0.05). RESULTS: Lowering the alumina content below
      0.25wt.% avoided the formation of alumina particles and therefore increased the
      translucency of 3Y-TZP ceramics, but the hydrothermal aging stability was
      reduced. A higher yttria content (5mol%) introduced about 50% cubic zirconia
      phase and gave rise to the most translucent and aging-resistant Y-TZP ceramics,
      but the fracture toughness and strength were considerably sacrificed. 0.2mol%
      La2O3 doping of 3Y-TZP tailored the grain boundary chemistry and significantly
      improved the aging resistance and translucency. Although the translucency
      improvement by La2O3 doping was less effective than for introducing a substantial
      amount of cubic zirconia, this strategy was able to maintain the mechanical
      properties of typical 3Y-TZP ceramics. SIGNIFICANCE: Three different approaches
      were compared to improve the translucency of 3Y-TZP ceramics.

PMID- 27697333
TI  - Lifetime prediction of zirconia and metal ceramic crowns loaded on marginal
      ridges.
AB  - OBJECTIVE: To evaluate the fatigue life of zirconia-veneered and metal-ceramic
      crowns comprised by an even thickness or a modified framework design when loaded
      on marginal ridges. METHODS: Eighty marginal ridges were present after
      fabrication of forty molar crowns cemented onto composite-resin replicas and
      divided (n=20/each), in the following groups: metal-ceramic with even thickness
      (MCev) or with a modified framework design (MCm, lingual collar with proximal
      struts); porcelain-fused to zirconia with even thickness (PFZev) or with the
      modified framework design (PFZm). Each marginal ridge (mesial and distal) was
      subjected to cyclic loading separately with a lithium disilicate indenter for 106
      cycles or until fracture. Kruskal-Wallis and Wilcoxon matched pair test (p<0.05)
      evaluated both marginal ridges. Every 125,000 cycles, the test was interrupted
      for damage inspection. Weibull distribution (90% confidence bounds) determined
      the probability of survival (reliability). RESULTS: Weibull 2-parameter contour
      plot showed significantly higher fatigue life for PFZev compared to MC, and
      comparable with PFZm. A significant decrease in reliability was observed between
      groups from 625,000 until 106 cycles. Metal-ceramic groups presented
      significantly lower probability of survival at 106 cycles (MCev=0.66% and
      MCm=4.73%) compared to PFZm (23.41%) and PFZev (36.68%). Fractographic marks
      showed a consistent fracture origin and direction of crack propagation.
      Reliability was higher for porcelain-fused to zirconia than for metal ceramic
      crowns, regardless of framework design. SIGNIFICANCE: Zirconia-veneered crowns
      presented decreased fracture rates compared to metal ceramics, even when loaded
      at marginal ridges, regardless of framework design.

PMID- 27697334
TI  - In Response to the Limited Utility of Screening Laboratory Tests and
      Electrocardiograms in the Management of Unintentional Asymptomatic Pediatric
      Ingestions.

PMID- 27697335
TI  - Vacuum Phenomenon as a Mechanism of Gas Production in the Abdominal Wall.

PMID- 27697336
TI  - Cost-effective and low-technology options for simulation and training in
      neonatology.
AB  - The purpose of this review is to explore low-cost options for simulation and
      training in neonatology. Numerous cost-effective options exist for simulation and
      training in neonatology. Lower cost options are available for teaching clinical
      skills and procedural training in neonatal intubation, chest tube insertion, and
      pericardiocentesis, among others. Cost-effective, low-cost options for simulation
      based education can be developed and shared in order to optimize the neonatal
      simulation training experience.

PMID- 27697337
TI  - Iron isotope fingerprints of redox and biogeochemical cycling in the soil-water
      rice plant system of a paddy field.
AB  - The iron isotope composition was used to investigate dissimilatory iron reduction
      (DIR) processes in an iron-rich waterlogged paddy soil, the iron uptake
      strategies of plants and its translocation in the different parts of the rice
      plant along its growth. Fe concentration and isotope composition (delta56Fe) in
      irrigation water, precipitates from irrigation water, soil, pore water solution
      at different depths under the surface water, iron plaque on rice roots, rice
      roots, stems, leaves and grains were measured. Over the 8.5-10cm of the vertical
      profiles investigated, the iron pore water concentration (0.01 to 24.3mg.l-1) and
      delta56Fe (-0.80 to -3.400/00) varied over a large range. The significant linear
      co-variation between Ln[Fe] and delta56Fe suggests an apparent Rayleigh-type
      behavior of the DIR processes. An average net fractionation factor between the
      pore water and the soil substrate of Delta56Fe~-1.150/00 was obtained, taking the
      average of all the delta56Fe values weighted by the amount of Fe for each sample.
      These results provide a robust field study confirmation of the conceptual model
      of Crosby et al. (2005, 2007) for interpreting the iron isotope fractionation
      observed during DIR, established from a series of laboratories experiments. In
      addition, the strong enrichment of heavy Fe isotope measured in the root relative
      to the soil solution suggest that the iron uptake by roots is more likely
      supplied by iron from plaque and not from the plant-available iron in the pore
      water. Opposite to what was previously observed for plants following strategy II
      for iron uptake from soils, an iron isotope fractionation factor of -0.90/00 was
      found from the roots to the rice grains, pointing to isotope fractionation during
      rice plant growth. All these features highlight the insights iron isotope
      composition provides into the biogeochemical Fe cycling in the soil-water-rice
      plant systems studied in nature.

PMID- 27697338
TI  - Trace element concentrations, risks and their correlation with metallothionein
      genes polymorphism: A case study of narrow-ridged finless porpoises (Neophocaena
      asiaeorientalis) in the East China Sea.
AB  - The concentration of trace elements (TEs) and their risk to narrow-ridged finless
      porpoises (Neophocaena asiaeorientalis) are still unclear. The present study
      determined the concentration of typical TEs in liver, kidney, and muscle tissues
      from porpoises in the East China Sea, assessed potential health risk of TEs to
      porpoises, and explored the relationship between TE concentration and
      metallothionein genes (MTs) polymorphism. It was found that Zn, Cu, Mn, Cd and Hg
      were highly accumulated in liver, and Cd was highly accumulated in kidney. The
      concentrations of Cr, As, Pb and Ni were very low in all three tissues. TE
      concentrations showed significant positive correlation with body length, and
      sexual variation. The levels of most TEs were higher in tissues of porpoises in
      Ningbo and Nantong than in Pingtan, which is likely related to the local
      environment pollution level. The risk assessment showed that porpoises from
      Nantong and Ningbo could face health risks due to Hg, As, Cd, Pb, and Cr
      exposure. Moreover, two polymorphic sites on the MT4 gene were found to be
      significantly associated with increased levels of Hg, Cd, Zn and Mn. Whether
      these two polymorphic sites are involved in expression of MTs, or other
      functional processes, needs further research.

PMID- 27697339
TI  - Linking current river pollution to historical pesticide use: Insights for
      territorial management?
AB  - Persistent organic pollutants like organochlorine pesticides continue to
      contaminate large areas worldwide raising questions concerning their management.
      We designed and tested a method to link soil and water pollution in the watershed
      of the Galion River in Martinique. We first estimated the risk of soil
      contamination by chlordecone by referring to past use of land for banana
      cultivation and took 27 soil samples. We then sampled surface waters at 39 points
      and groundwater at 16 points. We tested three hypotheses linked to the source of
      chlordecone pollution at the watershed scale: (i) soils close to the river, (ii)
      soils close to the sampling point, (iii) throughout the sub-watershed generated
      at the sampling point. Graphical and statistical analysis showed that
      contamination of the river increased when it passed through an area with
      contaminated plots and decreased when it passed through area not contaminated by
      chlordecone. Modeling showed that the entire surface area of the watershed
      contributed to river pollution, suggesting that the river was mainly being
      contaminated by the aquifers and groundwater flows. Our method proved to be a
      reliable way to identify areas polluted by chlordecone at the watershed scale and
      should help stakeholders focus their management actions on both hot spots and the
      whole watershed.

PMID- 27697340
TI  - Nitrogen deposition to forest ecosystems with focus on its different forms.
AB  - : Time trends and spatial patterns for wet nitrogen deposition in view of its
      reduced and oxidized forms for Czech forests are presented. Time trends in NH4+,
      NO3-, and N-NH4+/N-NO3- ratio at 15 sites in 1990-2014 were analysed using the
      Mann-Kendal test. Changes in spatial patterns derived from results of 43 sites in
      2005-2014 were also assessed. Our results indicated a slow but convincing change
      in favour of NH4+. The N-NH4+/N-NO3- ratio, both in precipitation and wet
      deposition, has been increasing steadily, reflecting the changes in reduced and
      oxidized forms of nitrogen emissions. A similar change has been observed in some
      other regions and might have negative impacts on ecosystems. CAPSULE: N-NH4+/N
      NO3- ratio in precipitation and deposition changes in favour of NH4+. This
      reflects changes in emissions and might have implications for ecosystems.

PMID- 27697341
TI  - Transfer, tissue distribution and bioaccumulation of microcystin LR in the
      phytoplanktivorous and carnivorous fish in Anzali wetland, with potential health
      risks to humans.
AB  - This study was conducted to determine Microcystin LR concentration in the aquatic
      ecosystem of the Anzali wetland in Iran. Extraction and detection of MC-LR from
      the water and fish samples was conducted by the SPE and HPLC-UV apparatus. Our
      results showed that among toxic cyanobacteria, Anabaena was the dominant genera
      during the study period. The results indicated that MC-LR content in water ranged
      from 0.18 to 3.02MUg/L in dissolved fraction and undetectable level to 1.13MUg/L
      in cellular fraction, in all three seasons. The results of PCA revealed that the
      environmental parameters including EC, Chl-a, PO43-, pH and temperature were the
      most effective factors influencing the MC-LR production. Results further showed
      the mean concentration of MC-LR in muscle and liver of silver carp ranged from
      10.12 to 40.98 and from undetectable to 44.34MUg/kg w.w, respectively. The mean
      concentration of MC-LR in northern pike was 15.18 to 35.1MUg/kg w.w in muscle and
      undetectable to 51.91MUg/kg w.w in liver samples. Our results suggest that
      consumption of fish harvested from the Anzali wetland seems to be unsafe for
      humans, based on obtained estimated daily intake values which were higher than
      the tolerable daily intake value recommended by WHO. In addition, bioaccumulation
      factor of MC-LR in edible tissues of fish was estimated based on lipid
      normalization. The results showed that the BAF of MC-LR in silver carp (1047+/
      185L/kg of lipid) was lower than the northern pike (1272+/-185L/kg of lipid),
      although the difference was not significant.

PMID- 27697342
TI  - Urbanization-related changes in soil PAHs and potential health risks of emission
      sources in a township in Southern Jiangsu, China.
AB  - Urbanization, which is characterized by population aggregation, industrial
      development, and increased traffic load, may change local polycyclic aromatic
      hydrocarbons (PAH) emissions and their associated health risks. To investigate
      these changes, we collected soil samples in 2009 and 2014 in a rapidly developing
      small town in Southern Jiangsu (China) and measured the concentrations of 16 PAHs
      via gas chromatography-mass spectrometry. Although the total PAHs decreased from
      4586.6 to 640.6ng/g, the concentrations of the high-molecular-weight PAHs
      benzo(b)fluoranthene and benzo(a)pyrene increased due to changes in the PAH
      sources. Source apportionment by positive matrix factorization indicated that the
      two sources responsible for the highest soil PAH contributions changed from
      biomass combustion (42%) and coal combustion (32%) in 2009 to coal, biomass and
      natural gas combustion (35%) and diesel combustion (33%) in 2014. However, the
      two sources with the highest associated health risks were diesel and gasoline
      combustion in both years. The incremental lifetime cancer risk for residents
      exposed to PAHs in the soil via incidental ingestion and dermal contact decreased
      from 1.75*10-6 to 1.60*10-6. The ban on open burning of straw and the
      substitution of coal with natural gas offset the PAH health risks due to
      increased urbanization.

PMID- 27697344
TI  - Sources and mass inventory of sedimentary polycyclic aromatic hydrocarbons in the
      Gulf of Thailand: Implications for pathways and energy structure in SE Asia.
AB  - Surface sediments obtained from a matrix of 92 sample sites in the Gulf of
      Thailand (GOT) were analyzed for a comprehensive study of the distribution,
      sources, and mass inventory of polycyclic aromatic hydrocarbons (PAHs) to assess
      their input pathways and impacts of the regional land-based energy structure on
      the deposition of PAHs on the adjacent continental margins. The concentration of
      16 PAHs in the GOT ranged from 2.6 to 78.1ng/g (dry weight), and the mean
      concentration was 19.4+/-15.1ng/g. The spatial distribution pattern of 16 PAH was
      generally consistent with that of sediment grain size, suggesting the influence
      of regional hydrodynamic conditions. Correlation and principal component analysis
      of the PAHs indicated that direct land-based inputs were dominantly responsible
      for the occurrence of PAHs in the upper GOT and the low molecular weight (LMW)
      PAHs in the coastal region could be from petrogenic sources. A positive matrix
      factorization (PMF) model apportioned five contributors: petroleum residues
      (~44%), biomass burning (~13%), vehicular emissions (~11%), coal combustion
      (~6%), and air-water exchange (~25%). Gas absorption may be a significant
      external input pathway for the volatile PAHs in the open GOT, which further
      implies that atmospheric loading could be important for the sink of PAHs in the
      open sea of the Southeast Asia (SE Asia). The different PAH source patterns
      obtained and a significant disparity of PAH mass inventory in the sediments along
      the East and Southeast Asia continental margins can be ascribed mainly to
      different land-based PAH emission features under the varied regional energy
      structure in addition to the depositional environment and climatic conditions.

PMID- 27697343
TI  - Occurrence, profile and spatial distribution of organochlorines pesticides in
      soil of Nepal: Implication for source apportionment and health risk assessment.
AB  - Nepal is a landlocked country located between world's two most populous countries
      India and China where high level of organochlorines pesticides has been reported
      from multi-environmental matrices. In this study, we investigated the occurrence,
      distributions and profile of selected OCP chemicals in surface soil samples
      (N=72) from four major cities of Nepal. Overall, the sum of total OCPs in soil
      ranged from 20 to 250ng/g with Biratnagar being the most polluted site in Nepal.
      DDTs and endosulfans were the most abundant OCP chemicals in soil samples. The
      concentration of DDTs ranged from 8 to 230ng/g, 8-56ng/g, 8-63ng/g, and 8-27ng/g
      in surface soil, while endosulfans were in the range of 2.9-3.3ng/g, 2.8-8.7ng/g,
      2.8-3.4ng/g, 2.8-3.2ng/g in Biratnagar, Kathmandu, Pokhara and Birgunj,
      respectively. The isomeric ratio of DDT and their metabolites suggested the
      ongoing usages of technical DDT as well as dicofol in this region. Lower ratio of
      alpha/beta-endosulfan indicated past application of endosulfans in Nepal. HCHs
      were less detected OCPs in soil sample accounting only 4-9% of ?OCPs. The
      isomeric ratio of alpha-/gamma-HCH indicated that the HCHs may be originated from
      mixed source of technical HCH as well as lindane use. Scattered plot of TOC and
      BC showed they were weakly and positively related with concentration of OCPs in
      soil. Health risk assessment modeling study of OCPs in soil suggested moderate
      cancer risk with ingestion being the most potential pathway of OCPs exposure.

PMID- 27697345
TI  - Investigation of chlorinated solvent pollution with resistivity and induced
      polarization.
AB  - Globally, an enormous number of polluted areas are in need of remediation to
      prevent adverse effects on health and environment. In situ remediation and
      especially the monitoring thereof needs further development to avoid costly and
      hazardous shipments associated with excavation. The monitoring of in situ
      remediation actions needs easier and cheaper nondestructive methods for
      evaluation and verification of remediation degree and degradation status of the
      contaminants. We investigate the Direct Current resistivity and time-domain
      Induced Polarization tomography (DCIP) method and its use within the context of a
      DNAPL (Dense Non-Aqueous Phase Liquids) contaminated site in Varberg, Sweden,
      where an in situ remediation pilot test has been performed by stimulated
      reductive dechlorination by push injection. Our results show that the DCIP
      technique is an emerging and promising technique for mapping of underground
      structures and possibly biogeochemical spatial and temporal changes. The
      methodology could in combination with drilling, sampling and other complementary
      methods give an almost continuous image of the underground structures and
      delineation of the pollutant situation. It can be expected to have a future in
      monitoring approaches measuring time lapse induced polarization (IP), if more
      research is performed on the parameters and processes affecting the IP-signals
      verifying the interpretations. The IP technique can possibly be used for
      verification of the effectiveness of in situ remediation actions, as the current
      sampling methodology is inadequate.

PMID- 27697346
TI  - Effects of land use/land cover on diurnal temperature range in the temperate
      grassland region of China.
AB  - As a fragile ecological zone, the temperate grassland region of China has
      experienced dramatic land use/land cover (LULC) changes due to human
      disturbances. So far, the impacts of LULC change on climate especially the
      diurnal temperature range (DTR) in this region are still not well understood.
      Based on the OMR (observation minus reanalysis) method, this study investigated
      the effects of LULC on DTR in the temperate grassland region of China.
      Considering the possible uncertainty of the results due to spatial resolution of
      the reanalysis dataset, two reanalysis datasets with different spatial
      resolutions were utilized. Results showed that LULC generally contributed to the
      decline of DTR in the temperate grassland region of China during 1980 to 2005.
      Due to different warming effects on monthly maximum temperature (Tmax) and
      minimum temperature (Tmin), grassland and forest tend to slightly decrease
      monthly DTR (approximately -0.053 to -0.050 degrees C/decade and approximately 
      0.059 to -0.055 degrees C/decade, respectively), while bare land has a slightly
      positive effect on DTR (approximately 0.018-0.021 degrees C/decade). By contrast,
      cropland and urban tend to slightly decrease Tmax, obviously increase Tmin and
      thus result in a rapid decline of DTR (approximately -0.556 to -0.503 degrees
      C/decade and approximately -0.617 to -0.612 degrees C/decade, respectively). In
      the temperate grassland region of China, grassland vegetation changes due to
      human disturbances can have some effects on DTR mainly by changing the Tmax.
      Conversion from grassland to cropland could decrease the DTR by slowing down the
      increase of Tmax. But the conversion from grassland to bare land, as well as the
      reduction of grassland vegetation cover will increase Tmax, and consequently the
      DTR. The results suggest that grassland degradation is likely to result in
      daylight warming and increased DTR in the temperate grassland region of China.

PMID- 27697347
TI  - Arbuscular mycorrhizal fungal assemblages in biological crusts from a Neotropical
      savanna are not related to the dominant perennial Trachypogon.
AB  - Knowledge of the arbuscular mycorrhizal fungal assemblages in the Trachypogon
      savanna ecosystems is very important to a better understanding of the ecological
      processes mediated by this soil microbial group that affects multiple ecosystem
      functions. Considering the hypothesis that the biocrusts can be linked to
      vegetation through the arbuscular fungi mycelial network, the objectives proposed
      in this study were to determine (i) whether there are arbuscular mycorrhizal
      fungi (AMF) in the biocrusts (ii) whether arbuscular mycorrhizal fungal
      assemblages are linked to the Trachypogon patches, and (iii) whether the
      composition of the assemblages is related to soil properties affected by
      microbiological activity. The community structure of the AMF was investigated in
      three habitats: rhizospheric soil and roots of Trachypogon vestitus, biological
      soil crusts, and bare soil. The canonical correspondence analysis showed that two
      soil properties related to enzymatic activity (protease and beta-glucosidase)
      significantly affected the community composition of the AMF. The biocrusts in the
      Venezuelan savanna are colonized by an AM fungal community linked to that of the
      bare soil and significantly different from that hosted by the roots of the
      surrounding T. vestitus, suggesting that assemblages of AMF in biocrusts might be
      related more closely to those of annual plant species appearing in favorable
      conditions.

PMID- 27697348
TI  - Towards a better pesticide policy for the European Union.
AB  - This opinion article aims to foster the debate about pesticide legislation in the
      European Union (EU). Numerous formerly authorized and widely used pesticides are
      now banned in the EU because unexpected and unacceptable risks emerged after
      their initial introduction to the market. Throughout this time lapse,
      environmental quality and human health have been threatened by the use of these
      compounds. These hazards could have been prevented by a more responsive pesticide
      regulatory framework. This article provides detailed insights into the pros and
      cons of pesticides, and points out weaknesses of the current pesticide
      environmental risk assessment procedures. Possibilities for improving the
      robustness and reliability of the pesticide regulatory framework are discussed.

PMID- 27697349
TI  - Sustainable use of veterinary pharmaceuticals on the territory (Sust-PHarm):
      Linking available database of manure management and environmental fate models.
AB  - Analogously to the evolution of the EU legislation on pesticides, there is an
      increasing need of strategies aiming to reach a "sustainable use of veterinary
      pharmaceuticals". To this end, it is essential to develop tools, such as
      supporting information systems (SIS), for managing the environmental risks of
      veterinary pharmaceuticals on a territorial scale. In this context, we propose
      Sust-PHarm (SUSTainable use of veterinary Pharmaceuticals), a SIS useful to
      identify groundwater vulnerable areas to veterinary pharmaceuticals at both local
      and regional scale. As background, Sust-PHarm follows the schemes of SIS for
      pesticides. The latter are based on the integration of predictive models in GIS.
      The proposed approach goes a step forward by integrating also data on the
      typologies of livestock farm, their spatial distribution and manure management
      techniques. This information allows to identify the potential environmental loads
      of veterinary pharmaceuticals. In this paper, we discuss the innovative elements
      characterizing Sust-PHarm through a comparison with the SIS currently used for
      pesticides. The advantages of Sust-PHarm are discussed using Lombardia Region
      (Northern Italy) as a case study. Simulations were made on 12 veterinary
      pharmaceuticals characterized by different physical-chemical properties. Results
      are compared with the current guidelines for the evaluation of veterinary
      pharmaceuticals leaching highlighting some substantial differences when realistic
      data are utilized making our approach more accurate than guidelines one.

PMID- 27697350
TI  - The influence of the autochthonous wastewater microbiota and gene host on the
      fate of invasive antibiotic resistance genes.
AB  - The aim of this study was to assess the fate of invasive antibiotic resistance
      genes (ARG) discharged in wastewater. With this objective, antibiotic resistant
      bacteria (ARB) known to harbor specific ARG were inoculated in wastewater
      (hospital effluent, or municipal raw and treated wastewater) and in ultra-pure
      sterile water microcosms. Two sets of wastewater ARB isolates were used - set 1,
      Enterococcus faecalis, Acinetobacter johnsonii, Klebsiella pneumoniae and set 2,
      Enterococcus faecium, Acinetobacter johnsonii, Escherichia coli. Non-inoculated
      controls were run in parallel. Samples were collected at the beginning and at the
      end (15days) of the incubation period and the abundance of the genes 16S rRNA,
      intI1, blaTEM and vanA and the bacterial community composition were analyzed. In
      general, the genes blaTEM and vanA had lower persistence in wastewater and in
      ultra-pure water than the genes 16S rRNA or the class 1 integron integrase intI1.
      This effect was more pronounced in wastewater than in ultra-pure water,
      evidencing the importance of the autochthonous microbiota on the elimination of
      invasive ARG. Wastewater autochthonous bacterial groups most correlated with
      variations of the genes intI1, blaTEM and vanA were members of the classes
      Gammaproteobacteria, Bacilli or Bacteroidia. For blaTEM, but not for vanA, the
      species of the ARB host was important to determine its fate. These are novel
      findings on the ecology of ARB in wastewater environments.

PMID- 27697351
TI  - Effect of water quality improvement on the remediation of river sediment due to
      the addition of calcium nitrate.
AB  - In situ sediment remediation technique is commonly used to control the release of
      pollutants from sediment. Addition of calcium nitrate to sediment has been
      applied to control the release of phosphorus from sediments. In this study,
      laboratory experiments were conducted to investigate the effect of water quality
      improvement on the remediation of river sediment with the addition of calcium
      nitrate. The results demonstrated that the redox-potential of sediments increased
      from -282mV to -130mV after 28days of calcium nitrate treatment. The acid
      volatile sulphide in the sediments significantly decreased (by 54.9% to 57.1%),
      whereas the total organic carbon decreased by 9.7% to 10.2%. However, the
      difference between these and water quality improvement was not significant. Due
      to the addition of calcium nitrate, low phosphate concentration in the water
      column and interstitial phosphate in the sediment were observed, indicating that
      the calcium nitrate was beneficial to controlling the release of phosphorus from
      river sediment. The decrease in phosphorus release could be attributed to the
      fixation of iron-phosphorus and calcium-phosphorus due to the addition of calcium
      nitrate. The addition of calcium nitrate to sediment caused the oxidation of
      sulphide to sulphate, hence resulting in high nitrate and sulphate concentrations
      in the water column, and high interstitial nitrate and sulphate concentrations in
      the sediment. The results also showed that only the water quality improvement had
      a significant effect on the interstitial nitrate and sulphate concentrations in
      the sediment.

PMID- 27697352
TI  - Return to sexual activity after myocardial infarction - An analysis of the level
      of knowledge in men undergoing cardiac rehabilitation.

PMID- 27697353
TI  - Acute effect of dark chocolate on red blood cell distribution width.

PMID- 27697354
TI  - [Comparison of transforaminal and interlaminar epidural steroid injections for
      the treatment of chronic lumbar pain].
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVE: We compared the 12 month
      outcomes of fluoroscopically guided transforaminal epidural steroid injections
      with interlaminar epidural steroid injections for the treatment of chronic lumbar
      spinal pain. Chronic lower back pain is a multifactorial disorder with many
      possible etiologies. The lifetime prevalence of spinal pain is reportedly 65-80%
      in the neck and lower back. Epidural injection of corticosteroids is a commonly
      used intervention for managing chronic spinal pain. METHODS: Patients who did not
      benefit from previous treatments were included in this study. Injections were
      performed according to magnetic resonance imaging findings at the nearest level
      of lumbar pathology; 173 patients received interlaminar epidural steroid
      injections and 126 patients received transforaminal epidural steroid injections.
      All of the patients were regularly followed up for 12 months using a verbal
      numeric rating scale. Magnetic resonance imaging findings, complications, verbal
      numeric rating scale, and satisfaction scores were recorded. RESULTS: Lumbar disk
      pathology was the most frequently encountered problem. The interlaminar epidural
      steroid injections were preferred at the L4-L5 intervertebral level. Verbal
      numeric rating scale scores significantly decreased during the 12-month period
      compared to basal scores (p<0.001). Significant differences between the two
      groups according to verbal numeric rating scale and satisfaction scores were not
      observed (p>0.05). There were no major complications; however, the interlaminar
      epidural steroid injections group had 22 (12.7%) minor complications, and the
      transforaminal epidural steroid injections group had 12 (9.5%) minor
      complications. CONCLUSIONS: This study showed that interlaminar epidural steroid
      injections can be as effective as transforaminal epidural steroid injections when
      performed at the nearest level of lumbar pathology using fluoroscopy in 12-month
      intervals.

PMID- 27697356
TI  - Changing body temperature during aortic arch surgery.

PMID- 27697357
TI  - Right internal thoracic artery or radial artery? A propensity-matched comparison
      on the second-best arterial conduit.
AB  - OBJECTIVES: We conducted propensity score matching to determine whether the use
      of the right internal thoracic artery (RITA) confers a survival advantage when
      compared with the radial artery (RA) as second arterial conduit in coronary
      artery bypass grafting. METHODS: The study population included a highly selected
      low-risk group of patients who received the RITA (n = 764) or the RA (n = 1990)
      as second arterial conduit. We obtained 764 matched pairs that were comparable
      for all pretreatment variables. A time-segmented Cox regression model that
      stratified on the matched pairs was used to investigate the effect of treatment
      on late mortality. RESULTS: After a mean follow-up of 10.2 +/- 4.5 years (maximum
      17.3 years), survival probabilities at 5, 10, and 15 years were 96.4% +/- 0.7%
      versus 95.4% +/- 0.7%, 91.0% +/- 1.1% versus 89.1% +/- 1.2%, and 82.4% +/- 1.9%
      versus 77.2% +/- 2.5% in the RITA and RA groups, respectively. During the first 4
      years, RITA and RA were comparable in terms of mortality (hazard ratio [HR],
      1.00; 95% confidence interval [CI], 0.56-1.78; P = .98). However, after 4 years
      RITA was associated with a significant reduction in late mortality (HR, 0.67; 95%
      CI, 0.48-0.95; P = .02). RITA was superior to RA when the experimental conduit
      was used to graft the left coronary system (HR, 0.69; 95% CI, 0.47-0.99; P = .04)
      but not the right coronary system (HR, 0.98; 95% CI, 0.59-1.62; P = .93).
      CONCLUSIONS: In a highly selected low-risk group of patients, the use of the RITA
      as second arterial conduit instead of the RA was associated with better survival
      when used to graft the left but not the right coronary artery.

PMID- 27697358
TI  - Prediction of prolonged mechanical ventilation after cardiac surgery: An
      imperfect crystal ball.

PMID- 27697359
TI  - Mast cell activation and arterial hypotension during proximal aortic repair
      requiring hypothermic circulatory arrest.
AB  - OBJECTIVE: Aortic surgeries requiring hypothermic circulatory arrest evoke
      systemic inflammatory responses that often manifest as vasoplegia and
      hypotension. Because mast cells can rapidly release vasoactive and
      proinflammatory effectors, we investigated their role in intraoperative
      hypotension. METHODS: We studied 31 patients undergoing proximal aortic repair
      with hypothermic circulatory arrest between June 2013 and April 2015 at Duke
      University Medical Center. Plasma samples were obtained at different
      intraoperative time points to quantify chymase, interleukin-6, interleukin-8,
      tumor necrosis factor alpha, and white blood cell CD11b expression. Hypotension
      was defined as the area (minutes * millimeters mercury) below a mean arterial
      pressure of 55 mm Hg. Biomarker responses and their association with
      intraoperative hypotension were analyzed by 2-sample t test and Wilcoxon rank sum
      test. Multivariable logistic regression analysis was used to examine the
      association between clinical variables and elevated chymase levels. RESULTS: Mast
      cell-specific chymase increased from a median 0.97 pg/mg (interquartile range
      [IQR], 0.01-1.84 pg/mg) plasma protein at baseline to 5.74 pg/mg (IQR, 2.91-9.48
      pg/mg) plasma protein after instituting cardiopulmonary bypass, 6.16 pg/mg (IQR,
      3.60-9.41 pg/mg) plasma protein after completing circulatory arrest, and 7.64
      pg/mg (IQR, 4.63-12.71 pg/mg) plasma protein after weaning from cardiopulmonary
      bypass (each P value < .0001 vs baseline). Chymase was the only biomarker
      associated with hypotension during (P = .0255) and after (P = .0221)
      cardiopulmonary bypass. Increased temperatures at circulatory arrest and low
      presurgical hemoglobin levels were independent predictors of increased chymase
      responses. CONCLUSIONS: Mast cell activation occurs in cardiac surgery requiring
      cardiopulmonary bypass and hypothermic circulatory arrest and is associated with
      intraoperative hypotension.

PMID- 27697360
TI  - Mid-term durability of the Trifecta bioprosthesis for aortic valve replacement.
AB  - OBJECTIVE: To clarify the mid-term durability of the Trifecta bioprosthesis for
      aortic valve replacement (AVR). METHODS: We retrospectively analyzed the
      prospectively collected data of 824 consecutive implants of the Trifecta valve at
      a single institution. A 100% complete follow-up was available (average duration,
      2.2 +/- 1.3 years; range, 0.03-6.9 years; 1747.6 patient-years). Echocardiography
      data at discharge were recorded prospectively. RESULTS: Operative mortality was
      3.8%; 2.7% in patients receiving isolated AVR. There were 5 valve-related early
      reoperations, including 1 for infective prosthetic endocarditis and 4 for
      nonstructural valve dysfunction. The global rate of severe patient-prosthesis
      mismatch was 1.26%. Overall 5-year survival was 74.9%, and freedom from valve
      related death was 97.8%. The majority of deaths attributed to the valve were due
      to unknown causes. We observed 6 SVD events at 3.4 +/- 1.6 years after surgery.
      At 5 years, the actuarial freedom from SVD was 98% +/- 0.9% (n = 6), freedom from
      reintervention for SVD was 98% +/- 0.9% (n = 5, including 2 transcatheter valve
      in-valve), and freedom from open reoperation for SVD was 98.9% +/- 0.6%. The 5
      year freedom from prosthetic endocarditis was 97.7% +/- 0.7% (n = 12, 6 requiring
      reoperation). There was 1 case of late NSVD (5-year freedom, 99.8% +/- 0.2%).
      Freedom from hemorrhagic events was 98.6% +/- 0.5% (86% occurring in patients on
      anticoagulants); there were no thromboembolic events at follow-up. CONCLUSIONS:
      The Trifecta bioprosthesis is a reliable device for AVR. We confirm excellent
      immediate hemodynamic properties and a very low rate of patient-prosthesis
      mismatch. The absolute number of SVD cases observed remains limited;
      nevertheless, their timing, pathological characteristics, and clinical
      presentation mandate continued follow-up.

PMID- 27697361
TI  - Unsuspected Malignancies in Routine Femoral Head Histopathologic Examination
      During Primary Total Hip Arthroplasty: Cost-Effectiveness Analysis.
AB  - BACKGROUND: Routine femoral head histopathology during primary total hip
      arthroplasty (THA) has been recently reported as a potentially useful screening
      tool for bone- and bone marrow-associated malignancies. However, cost
      effectiveness of routine histopathology during THA remains unclear due to low
      prevalence of significant medical findings which alter patient management. The
      aim of this study was to evaluate the cost-effectiveness of routine
      histopathology in diagnosing unsuspected malignancy in patients undergoing
      primary THA. METHODS: From 1993 to 2011, we retrospectively analyzed routine
      histopathologic findings of 3200 femoral head specimens from 2725 patients that
      underwent primary THA. Preoperative and postoperative diagnoses were classified
      into concordant (clinical diagnosis concurred with pathologic diagnosis),
      discrepant (differing diagnosis with no resultant impact on patient management),
      and discordant (differing diagnosis with subsequent change in patient
      management). Cost-effectiveness analysis was performed using the incremental cost
      utility ratio. RESULTS: A total of 3055 of 3200 pathologic samples were
      concordant with the preoperative diagnosis (95.4%), 140 of 3200 were discrepant
      (4.4%), and 5 of 3200 were discordant (0.2%). Routine histopathology revealed 1
      unsuspected malignancy out of 640 (5 of 3200) femoral heads. The total cost of
      histopathologic screening was $614,664.80. The average cost to identify a
      discrepant case was $4390.46, and the cost to identify a discordant case was
      $122,932.96. The incremental cost-utility ratio was $49,569.74 per quality
      adjusted life year (QALY) gained. CONCLUSION: Our study indicates routine femoral
      head histopathology may be cost-effective in diagnosing unsuspected malignancy at
      $49,569.74/QALY gained (less than World Health Organization recommended threshold
      $159,000/QALY gained), providing useful clinical information for surgeons
      considering the value of routine femoral head histopathology in patients
      undergoing THA.

PMID- 27697362
TI  - Collaborative study for the calibration of a replacement International Standard
      for diphtheria toxoid for use in flocculation test.
AB  - We present the results of a collaborative study for the establishment of a
      replacement International Standard (IS) for diphtheria toxoid for use in
      flocculation test and its calibration in Lf units. Calibration was performed
      using Ramon flocculation method, standardized using the 2nd IS. The candidate
      standard was assigned a unitage of 1870 Lf/ampoule based on results from 25
      laboratories in 15 different countries and was established as the 3rd IS for
      diphtheria toxoid for use in flocculation test by the WHO Expert Committee on
      Biological Standardization (ECBS) in October 2015. The study also assessed the
      use of alternative methods for measuring Lf. Participants were asked to determine
      the Lf value of the candidate standard using an Enzyme Linked Immunosorbent Assay
      (ELISA) established at NIBSC, or other suitable in-house method. 10 laboratories
      performed ELISA according to the NIBSC protocol, 1 laboratory performed
      flocculation using laser-light scattering according to an in-house protocol, and
      1 laboratory performed another in-house ELISA. Results suggest these methods may
      provide suitable alternatives to the Ramon flocculation test, subject to
      validation, and that the new standard could act as a suitable reference
      preparation in these methods.

PMID- 27697363
TI  - Characterization of Vibrio parahaemolyticus and its specific phage from shrimp
      pond in Palk Strait, South East coast of India.
AB  - Phage therapy is an alternative and eco-friendly biocontrol agent to prevent and
      control multidrug resistant bacteria in the aquatic system. The aim of this study
      is to isolate and characterize the Vibrio parahaemolyticus and its potential
      lytic phage from Penaeus monodon growing-out by rearing in shrimp ponds in Palk
      Strait, South East coast of India. The conventional phenotypic characteristics
      and molecular identification was confirmed using 16S rRNA sequence and to
      determine the antibiotic resistant profiles. The V. parahaemolyticus phage was
      effective against V. parahaemolyticus through one-step growth experiments, phage
      survival was determined by long-term storage at various temperatures and pH.
      Further, transmission electron microscope (TEM) revealed that the lytic phage
      belongs to the Myoviridae family. The isolated lytic phage (VVP1) was more
      specific against N1A V. parahaemolyticus and was able to infect N7A V.
      parahaemolyticus, N3B and N13B Vibrio alginolyticus strains. Evaluation of
      microcosm studies with P. monodon larvae infected with V. parahaemolyticus showed
      the survival of larvae in the presence of phage treatment at 2.3 * 1010 PFU/mL-1
      was enhanced when compared with the control. This study provides the application
      of phage as a useful strategy to prevent and eliminate or reduce shrimp
      pathogenic V. parahaemolyticus in the aquaculture system.

PMID- 27697364
TI  - DNA damage response regulation by microRNAs as a therapeutic target in cancer.
AB  - The inability of cancer cells in taking care of DNA damages can lead to cancer
      development and/or progression. Due to the essential role of DNA repair in
      maintaining genomic stability, tightly controlled regulatory mechanism are
      required for these processes. Recent studies have shown a myriad of interactions
      among DNA damage response (DDR) components and miRNAs. While DDR modulates miRNA
      expression in transcriptional and post-transcriptional levels and affects miRNA
      degradation, miRNAs in turn, directly modulate the expression of multiple
      proteins in the DDR pathways, or indirectly fine-tune the expression of such
      proteins. A better understanding of DDR-miRNA interactions can facilitate the
      development of new anticancer agents targeting miRNAs involved in the DNA repair
      process. In this review, we provide a brief introduction about miRNA biogenesis
      and functions, DDR pathways, and recent findings about DDR-microRNA interactions.
      Finally, the therapeutic importance of miRNAs in modulation of DDR/DNA repair
      mechanisms will be discussed.

PMID- 27697365
TI  - Response to 'Re: Endovascular Therapy for Large Vessel Vasculopathy in HIV
      Infected Patients'.

PMID- 27697366
TI  - High carbohydrate diet induces nonalcoholic steato-hepatitis (NASH) in a desert
      gerbil.
AB  - A high intake of sugars has been linked to diet-induced health problems. The aim
      of this study was to assess whether the long-term consumption of a high
      carbohydrate diet (HCD) would cause the hepatic histopathological and metabolic
      abnormalities that characterize nonalcoholic steatohepatitis (NASH) in a desert
      gerbil, Gerbillus gerbillus. Compared to natural diet, HCD leads to several
      metabolic disorders including adiposity, dyslipidemia, insulin resistance,
      ectopic fat deposition in the liver, which were associated with higher levels of
      transcripts of genes involved with fat synthesis, endoplasmic reticulum (ER)
      stress, and fibrosis. In the same way, the experimented animals showed enhanced
      oxidative stress. Taken together, these results demonstrate that HCD consumption
      in gerbils induces metabolic disorders and damaged liver, which are key
      contributors to NASH development. These results suggest that this rodent
      represents a valuable natural model for human diet-induced metabolic disorders
      and nonalcoholic fatty liver disease (NAFLD).

PMID- 27697367
TI  - Genetic diversity and population structure of six species of Capparis in Tunisia
      using AFLP markers.
AB  - In order to study the genetic diversity, the phylogeographic pattern and
      hybridization between six Tunisian Capparis species, 213 accessions of Caper were
      genotyped with three primer combinations of amplified fragment length
      polymorphism (AFLP) markers. Out of 750 fragments generated, 636 were polymorphic
      and 407 of them were restricted to a single species. STRUCTURE and PCoA analyses
      clearly separated morphologically different populations into six distinct genetic
      ones. The UPGMA analysis grouped the species into three main clusters: G1 grouped
      C. spinosa subsp. spinosa var. spinosa and C. sicula subsp. sicula; G2 grouped C.
      ovata subsp. ovata and C. orientalis and G3 clustered C. zoharyi and C. aegyptia.
      Populations from G1, G2 and G3 were mainly distributed in arid, subhumid, and
      semi-arid bioclimates, respectively. Additional genetic studies on Capparis could
      help to identify genes underlying speciation events and local adaptation to
      geographic areas leading to the development of breeding programs.

PMID- 27697368
TI  - HIV Stigma and Social Capital in Women Living With HIV.
AB  - Women living with HIV (WLWH) continue to experience HIV-related stigma. Social
      capital is one resource that could mitigate HIV stigma. Our cross-sectional study
      examined associations between social capital and HIV-related stigma in 135 WLWH
      in the San Francisco Bay Area. The mean age of study participants was 48 years;
      60% were African American; 29% had less than a high school education; and 19%
      were employed. Age was significantly associated with perceived HIV stigma (p =
      .001), but total social capital was not. Women with lower Value of Life social
      capital scores had significantly higher total stigma scores (p = .010) and higher
      Negative Self-image stigma scores (p = .001). Women who felt less valued in their
      social worlds may have been more likely to perceive HIV stigma, which could have
      negative health consequences. This work begins to elucidate the possible
      relationships between social capital and perceived HIV stigma.

PMID- 27697369
TI  - Heart rate variability in patients with essential tremor: A cross sectional
      study.
AB  - OBJECTIVE: To investigate heart rate variability (HRV) in patients with Essential
      Tremor (ET) in comparison with patients with Parkinson's Disease (PD). METHODS:
      This is a cross sectional control study including 10 patients with ET, 10
      patients with PD and 10 age-sex-matched controls. In patients and controls, we
      measured the components of HRV analysis in the frequency domain during a daytime
      period of 12-h. Selected HRV variables were low-frequency (LF) and high-frequency
      (HF), conventionally considered to be influenced by the sympathetic system and
      the parasympathetic system respectively. RESULTS: HRV variables, in patients with
      ET, were significantly different from those detected in PD patients and similar
      to those of controls while in PD patients, they were significantly different from
      those of controls. At cut off level of 654 ms2, LF component correctly
      distinguished ET patients versus PD with sensitivity, specificity, PPV and
      accuracy of 100%. By contrast, at cut off level of 737 ms2, HF component showed
      sensitivity, specificity, PPV and accuracy of 80%, 100%, 100%, and 86.67%
      respectively. DAT-SPECT and cardiac MIBG uptake were both normal in ET patients
      whereas they were markedly decreased in those with PD. CONCLUSIONS: In our study,
      the LF component of HRV analysis distinguishes ET patients from those with PD on
      an individual basis, thus representing a valid help in everyday clinical practice
      for differentiation between these patients in absence of scintigraphic
      investigations.

PMID- 27697371
TI  - Evaluation of model-based methods in estimating respiratory mechanics in the
      presence of variable patient effort.
AB  - Monitoring of respiratory mechanics is required for guiding patient-specific
      mechanical ventilation settings in critical care. Many models of respiratory
      mechanics perform poorly in the presence of variable patient effort. Typical
      modelling approaches either attempt to mitigate the effect of the patient effort
      on the airway pressure waveforms, or attempt to capture the size and shape of the
      patient effort. This work analyses a range of methods to identify respiratory
      mechanics in volume controlled ventilation modes when there is patient effort.
      The models are compared using 4 Datasets, each with a sample of 30 breaths
      before, and 2-3 minutes after sedation has been administered. The sedation will
      reduce patient efforts, but the underlying pulmonary mechanical properties are
      unlikely to change during this short time. Model identified parameters from
      breathing cycles with patient effort are compared to breathing cycles that do not
      have patient effort. All models have advantages and disadvantages, so model
      selection may be specific to the respiratory mechanics application. However, in
      general, the combined method of iterative interpolative pressure reconstruction,
      and stacking multiple consecutive breaths together has the best performance over
      the Dataset. The variability of identified elastance when there is patient effort
      is the lowest with this method, and there is little systematic offset in
      identified mechanics when sedation is administered.

PMID- 27697370
TI  - Differential associations between Social Anxiety Disorder, family cohesion, and
      suicidality across racial/ethnic groups: Findings from the National Comorbidity
      Survey-Adolescent (NCS-A).
AB  - The proposed research seeks to introduce a novel model relating Social Anxiety
      Disorder (SAD) and suicide outcomes (i.e., passive suicidal ideation, active
      suicidal ideation, and suicide attempts) in diverse adolescents. This model
      posits that family cohesion is one pathway by which suicide risk is increased for
      socially anxious youth, and predicts that the relationships between these
      variables may be of different strength in Latino and White subgroups and across
      gender. Data from a sample of Latino (n=1922) and non-Hispanic White (hereafter
      referred to as White throughout) (n=5648) male and female adolescents who
      participated in the National Comorbidity Survey-Adolescent were used for this
      study. Analyses were conducted using generalized structural equation modeling.
      Results showed that the mediation model held for White females. Further
      examination of direct pathways highlighted SAD as a risk factor unique to Latinos
      for active suicidal ideation and suicide attempt, over and above comorbid
      depression and other relevant contextual factors. Additionally, family cohesion
      showed a strong association with suicide outcomes across groups, with some
      inconsistent findings for White males. Overall, it appears that the mechanism by
      which SAD increases risk for suicidality is different across groups, indicating
      further need to identify relevant mediators, especially for racial/ethnic
      minority youth.

PMID- 27697372
TI  - Assessing Methanobrevibacter smithii and Clostridium difficile as not
      conventional faecal indicators in effluents of a wastewater treatment plant
      integrated with sludge anaerobic digestion.
AB  - Wastewater treatment plants (WWTP) are an important source of surface water
      contamination by enteric pathogens, affecting the role of environmental water as
      a microbial reservoir. We describe the release to the environment of certain
      anaerobes of human and environmental concern. The work was focused on emerging
      microbial targets. They are tracing, by RT-qPCR, on WWTP effluents, both liquid
      and solid, when an anaerobic digestion step is included. The focus is placed on
      Clostridium spp. with the specific quantification of Clostridium perfringens, as
      typical bioindicator, and Clostridium difficile, as emerging pathogen not only
      confined into nosocomial infection. Moreover methanogens were quantified for
      their involvement in the anaerobic digestion, and in particular on
      Methanobrevibacter smithii as major methanogenic component of the human gut
      microbiome and as not conventional faecal indicator. In the water samples, a
      reduction, statistically significant, in all microbial targets was observed (p <
      0.01), 2 log for the total bacteria, 1.4 log for the Clostridium spp. and M.
      smithii, 1 log for total methanogens, C. perfringens and C. difficile. The AD
      process contribute to a significant change in microbial levels into the sludge
      for total bacteria and total methanogens (p < 0.01), both when the input sludge
      are primary and secondary, while for the presence of Clostridium spp. and C.
      difficile there was not a significant change. The produced data are innovative
      showing which is the diffusion of such anaerobic microorganisms throughout the
      WWTP and opening a discussion on the implementation of possible techniques for a
      more efficient microbial removal from effluents, particularly bio-solids, to
      reduce the potential release of pathogens into the environment.

PMID- 27697373
TI  - Managing land application of coal seam water: A field study of land amendment
      irrigation using saline-sodic and alkaline water on a Red Vertisol.
AB  - Coal seam (CS) gas operations coproduce water with gas from confined CS aquifers.
      This CS water represents a potential agricultural resource if the water is able
      to be chemically amended to comply with management guidelines. Stoichiometric
      quantities of sulphur and gypsum amendments can be used to neutralise the
      alkalinity and reduce the sodicity of CS water respectively. These amendments can
      either be mixed in-line at a water treatment plant or applied directly to land
      prior to the application of CS water (a practice termed land amendment irrigation
      - LAI). This study compared the efficacy of LAI with in-line chemical amendment
      of CS water and irrigation with non-saline, non-sodic and non-alkaline (good
      quality) water under field conditions in southern Queensland. Soil chemical
      properties, soluble Ca, Mg, K, Na, electrical conductivity (EC), pH, chloride and
      alkalinity, as well as saturated hydraulic conductivity were measured to
      determine the impact of the irrigation treatments on soil chemical and physical
      conditions. Irrigation of lucerne pasture using solid-set sprinklers applied a
      total of 6.7 ML/ha of each treatment irrigation water to the experimental plots
      over a 10-month period. Alkalinity was neutralised using LAI, with no increase in
      soil alkalinity observed. Soil sodicity did not exceed threshold electrolyte
      concentration values under either CS water irrigation treatment. Soil chemical
      and physical properties were comparable for both LAI and in-line chemical
      amendment of CS water. Soil saturated hydraulic conductivity was maintained under
      all irrigation treatments. Results showed that the constrained capacity of the
      irrigation system was unable to meet crop evapotranspiration demand. This
      resulted in accumulation of salt within the root-zone under the CS water
      treatments compared to the good quality water treatment. LAI successfully
      chemically amended Bowen Basin CS water facilitating its beneficial use for
      agricultural irrigation.

PMID- 27697374
TI  - Budding trends in integrated pest management using advanced micro- and nano
      materials: Challenges and perspectives.
AB  - One of the most vital supports to sustain human life on the planet earth is the
      agriculture system that has been constantly challenged in terms of yield. Crop
      losses due to insect pest attack even after excessive use of chemical pesticides,
      are major concerns for humanity and environment protection. By the virtue of
      unique properties possessed by micro and nano-structures, their implementation in
      Agri-biotechnology is largely anticipated. Hence, traditional pest management
      strategies are now forestalling the potential of micro and nanotechnology as an
      effective and viable approach to alleviate problems pertaining to pest control.
      These technological innovations hold promise to contribute enhanced productivity
      by providing novel agrochemical agents and delivery systems. Application of these
      systems engages to achieve: i) control release of agrochemicals, ii) site
      targeted delivery of active ingredients to manage specific pests, iii) reduced
      pesticide use, iv) detection of chemical residues, v) pesticide degradation, vi)
      nucleic acid delivery and vii) to mitigate post-harvest damage. Applications of
      micro and nano-technology are still marginal owing to the perception of low
      economic returns, stringent regulatory issues involving safety assessment and
      public awareness over their uses. In this review, we highlight the potential
      application of micro and nano-materials with a major focus on effective pest
      management strategies including safe handling of pesticides.

PMID- 27697375
TI  - Fate of sulfur mustard on soil: Evaporation, degradation, and vapor emission.
AB  - After application of sulfur mustard to the soil surface, its possible fate via
      evaporation, degradation following absorption, and vapor emission after
      decontamination was studied. We used a laboratory-sized wind tunnel, thermal
      desorber, gas chromatograph-mass spectrometry (GC-MS), and 13C nuclear magnetic
      resonance (13C NMR) for systematic analysis. When a drop of neat HD was deposited
      on the soil surface, it evaporated slowly while being absorbed immediately into
      the matrix. The initial evaporation or drying rates of the HD drop were found to
      be power-dependent on temperature and initial drop volume. Moreover, drops of
      neat HD, ranging in size from 1 to 6 MUL, applied to soil, evaporated at
      different rates, with the smaller drops evaporating relatively quicker. HD
      absorbed into soil remained for a month, degrading eventually to nontoxic
      thiodiglycol via hydrolysis through the formation of sulfonium ions. Finally, a
      vapor emission test was performed for HD contaminant after a decontamination
      process, the results of which suggest potential risk from the release of trace
      chemical quantities of HD into the environment.

PMID- 27697376
TI  - Complex mixtures of Pesticides in Midwest U.S. streams indicated by POCIS time
      integrating samplers.
AB  - The Midwest United States is an intensely agricultural region where pesticides in
      streams pose risks to aquatic biota, but temporal variability in pesticide
      concentrations makes characterization of their exposure to organisms challenging.
      To compensate for the effects of temporal variability, we deployed polar organic
      chemical integrative samplers (POCIS) in 100 small streams across the Midwest for
      about 5 weeks during summer 2013 and analyzed the extracts for 227 pesticide
      compounds. Analysis of water samples collected weekly for pesticides during POCIS
      deployment allowed for comparison of POCIS results with periodic water-sampling
      results. The median number of pesticides detected in POCIS extracts was 62, and
      141 compounds were detected at least once, indicating a high level of pesticide
      contamination of streams in the region. Sixty-five of the 141 compounds detected
      were pesticide degradates. Mean water concentrations estimated using published
      POCIS sampling rates strongly correlated with means of weekly water samples
      collected concurrently, however, the POCIS-estimated concentrations generally
      were lower than the measured water concentrations. Summed herbicide
      concentrations (units of ng/POCIS) were greater at agricultural sites than at
      urban sites but summed concentrations of insecticides and fungicides were greater
      at urban sites. Consistent with these differences, summed concentrations of
      herbicides correlate to percent cultivated crops in the watersheds and summed
      concentrations of insecticides and fungicides correlate to percent urban land
      use. With the exception of malathion concentrations at nine sites, POCIS
      estimated water concentrations of pesticides were lower than aquatic-life
      benchmarks. The POCIS provide an alternative approach to traditional water
      sampling for characterizing chronic exposure to pesticides in streams across the
      Midwest region.

PMID- 27697377
TI  - Electrochemical oxidation of the polycyclic aromatic hydrocarbons in polluted
      concrete of the residential buildings.
AB  - Polycyclic aromatic hydrocarbons (PAH) have been listed by the United States
      Environmental Protection Agency (US EPA) and by the European Community as
      priority environmental pollutants. The removal of PAHs from soils, sediments and
      waste water has attracted attention of scientists and engineers for several
      decades. Electrochemical oxidation of PAH compounds in water, is receiving
      increasing attention, due to its convenience and simplicity. In this study we
      performed electrochemical oxidation of 16 EPA PAHs mixture in 10% NaCl aqueous
      solution in potentiostatic conditions, at voltage 1 V. Decrease of concentration
      of some individual PAHs, up to 70% referred to their starting concentration,
      after 60 min of electrolysis, was confirmed by UPLC/PDA analysis. In further work
      investigation was extrapolated to in situ removal of PAHs from concrete, as the
      medium where, to our knowledge, such way of PAH removal has not been investigated
      before. High concentrations of PAH contamination occurred in the concrete
      structure of the residential buildings in Belgrade in 2014. Application of DC
      voltage of 50 V between nickel and stainless steel electrodes packed in the
      concrete wall, moisturized with the 10% NaCl solution, led to considerable
      removal of the pollutants by oxidation process throughout the concrete.

PMID- 27697379
TI  - Gold mining and mercury contamination in Peru.

PMID- 27697378
TI  - Carboxylesterase-involved metabolism of di-n-butyl phthalate in pumpkin
      (Cucurbita moschata) seedlings.
AB  - Uptake and accumulation by plants is a significant pathway in the migration and
      transformation of phthalate esters (PAEs) in the environment. However, limited
      information is available on the mechanisms of PAE metabolism in plants. Here, we
      investigated the metabolism of di-n-butyl phthalate (DnBP), one of the most
      frequently detected PAEs, in pumpkin (Cucurbita moschata) seedlings via a series
      of hydroponic experiments with an initial concentration of 10 mg L-1. DnBP
      hydrolysis occurred primarily in the root, and two of its metabolites, mono-n
      butyl phthalate (MnBP) and phthalic acid (PA), were detected in all plant
      tissues. The MnBP concentration was an order of magnitude higher than that of PA
      in shoots, which indicated MnBP was more readily transported to the shoot than
      was PA because of the former's dual hydrophilic and lipophilic characteristics.
      More than 80% of MnBP and PA were located in the cell water-soluble component
      except that 96% of MnBP was distributed into the two solid cellular fractions
      (i.e., cell wall and organelles) at 96 h. A 13-20% and 29-54% increase of
      carboxylesterase (CXE) activity shown in time-dependent and concentration
      dependent experiments, respectively, indicated the involvement of CXEs in plant
      metabolism of DnBP. The level of CXE activity in root subcellular fractions was
      in the order: the cell water-soluble component (88-94%) >> cell wall (3-7%) >
      cell organelles (3-4%), suggesting that the cell water-soluble component is the
      dominant locus of CXE activity and also the domain of CXE-catalyzed hydrolysis of
      DnBP. The addition of triphenyl phosphate, a CXE inhibitor, led to 43-56%
      inhibition of CXE activity and 16-25% increase of DnBP content, which
      demonstrated the involvement of CXEs in plant metabolism of DnBP. This study
      contributes to our understanding of enzymitic mechanisms of PAE transformation in
      plants.

PMID- 27697380
TI  - Developmental and neurotoxicity of the mosquito control larvicide.

PMID- 27697381
TI  - Presence of microplastic in the digestive tracts of European flounder,
      Platichthys flesus, and European smelt, Osmerus eperlanus, from the River Thames.
AB  - Like many urban catchments, the River Thames in London is contaminated with
      plastics. This pollutant is recorded on the river banks, in the benthic
      environment and in the water column. The present study was conducted to assess
      the extent of microplastic ingestion in two River Thames fish species, the
      European flounder (Platichthys flesus) and European smelt (Osmerus eperlanus).
      Samples were collected from two sites in Kent, England; Erith and Isle of
      Grain/Sheppey, near Sheerness, with the latter being more estuarine. The results
      revealed that up to 75% of sampled European flounder had plastic fibres in the
      gut compared with only 20% of smelt. This difference may be related to their
      diverse feeding behaviours: European flounder are benthic feeders whilst European
      smelt are pelagic predators. The fibres were predominantly red or black
      polyamides and other fibres included acrylic, nylon, polyethylene and
      polyethylene terephthalate and there was no difference in occurrence between the
      sites sampled.

PMID- 27697382
TI  - Effects of simulated acid rain on soil fauna community composition and their
      ecological niches.
AB  - Acid rain is one of the severest environmental issues globally. Relative to other
      global changes (e.g., warming, elevated atmospheric [CO2], and nitrogen
      deposition), however, acid rain has received less attention than its due. Soil
      fauna play important roles in multiple ecological processes, but how soil fauna
      community responds to acid rain remains less studied. This microcosm experiment
      was conducted using latosol with simulated acid rain (SAR) manipulations to
      observe potential changes in soil fauna community under acid rain stress. Four pH
      levels, i.e., pH 2.5, 3.5, 4.5, and 5.5, and a neutral control of pH 7.0 were set
      according to the current pH condition and acidification trend of precipitation in
      southern China. As expected, we observed that the SAR treatments induced changes
      in soil fauna community composition and their ecological niches in the tested
      soil; the treatment effects tended to increase as acidity increased. This could
      be attributable to the environmental stresses (such as acidity, porosity and
      oxygen supply) induced by the SAR treatments. In addition to direct acidity
      effect, we propose that potential changes in permeability and movability of water
      and oxygen in soils induced by acid rain could also give rise to the observed
      shifts in soil fauna community composition. These are most likely indirect
      pathways of acid rain to affect belowground community. Moreover, we found that
      nematodes, the dominating soil fauna group in this study, moved downwards to
      mitigate the stress of acid rain. This is probably detrimental to soil fauna in
      the long term, due to the relatively severer soil conditions in the deep than
      surface soil layer. Our results suggest that acid rain could change soil fauna
      community and the vertical distribution of soil fauna groups, consequently
      changing the underground ecosystem functions such as organic matter decomposition
      and greenhouse gas emissions.

PMID- 27697384
TI  - Predictive validity of a specific questionnaire for psychiatric morbidity and
      suicidal ideation.

PMID- 27697383
TI  - Acute exposure to fine particulate matter and cardiovascular hospital emergency
      room visits in Beijing, China.
AB  - Fine particulate matter (PM2.5) air pollution outbreaks have recently occurred
      frequently in China. However, evidence of the associations between short-term
      exposure to PM2.5 and cardiovascular morbidity is still limited in China. This
      study aimed to evaluate the associations between PM2.5 and hospital emergency
      room visits (ERVs) for cardiovascular diseases in urban areas in Beijing. Daily
      counts of cardiovascular ERVs were collected from ten large general hospitals
      from Jan 1 to Dec 31, 2013. Air pollution data were obtained from the Beijing
      Environmental Protection Bureau including 17 monitoring stations. A generalized
      additive Poisson model was used to examine the associations between PM2.5 and
      cardiovascular ERVs after controlling for seasonality, day of the week, public
      holidays, influenza outbreaks, and weather conditions. In total, there were
      56,221 cardiovascular ERVs during the study period. The daily mean PM2.5
      concentration was 102.1 MUg/m3, ranging from 6.7 MUg/m3 to 508.5 MUg/m3. Per 10
      MUg/m3 increase in PM2.5 was associated with a 0.14% (95% confidence interval
      [CI]: 0.01%-0.27%) increase in cardiovascular ERVs at lag3. Cumulative delayed
      estimates were greatest at lag0-5 (0.30%, 95% CI: 0.09%-0.52%). The estimates of
      percentage change in daily ERVs per 10 MUg/m3 increase in PM2.5 were 0.56%
      (95%CI: 0.16%-0.95%) for ischemic heart disease (IHD) at lag0-1, 0.81% (95%CI:
      0.05%-1.57%) for heart rhythm disturbances (HRD) at lag0-1 and 1.21% (95%CI:
      0.27%-2.15%) for heart failure (HF) at lag0, respectively. The effects of PM2.5
      on IHD ERVs during high temperature days (>11.01  degrees C) were significantly
      higher than that on low temperature days (<=11.01  degrees C) at lag0, lag0-1,
      lag0-3 and lag0-5 (P < 0.05). The study suggests that PM2.5 has acute impacts on
      cardiovascular ERVs in Beijing, especially on IHD, HRD and HF. The effects of
      PM2.5 on IHD ERVs vary by temperature.

PMID- 27697385
TI  - Have you cleaned your stethoscope today?

PMID- 27697386
TI  - The forensic analysis of office paper using oxygen Isotope Ratio Mass
      Spectrometry, part 2: Characterising the source materials and the effect of
      production and usage on the delta18O values of cellulose and paper.
AB  - For casework applications, understanding the source processes used to create a
      material and the effects of those sources on the results obtained by Isotope
      Ratio Mass Spectrometry (IRMS) of a bulk material is important. Likewise,
      understanding the effect of environment, home/office printing processes and some
      forensic testing in at least a basic context, ensures that in casework, enough
      information on the effects of these variables is available during comparison and
      interpretation. In this study, which focuses on oxygen isotopic abundance
      measurements, both fractionation and mixing effects were observed within the
      pulping and production process. Also observed in the carbon isotopic experiments,
      sampling that included toner changed the measured isotopic abundance values of
      the paper and should be avoided in casework. Inkjet printing processes were not
      shown to have an effect on the paper oxygen abundance values. Samples that were
      treated for fingerprints using 1,2-Indandione-Zn prior to sampling showed the
      greatest risk for misinterpretation of whether two samples had originated from
      the same source. While this study provides a good basis and understanding of the
      effects of a range of factors on document paper oxygen isotope values, further
      testing for a range of specific casework scenarios is required and should be
      undertaken on a case by case basis as the need arises.

PMID- 27697387
TI  - Reply to Williamson S.R. What is the malignant potential of clear cell papillary
      renal cell carcinoma? Urol Oncol 2016; 34: 420.

PMID- 27697389
TI  - Effects of prophylactic knee bracing on knee joint kinetics and kinematics during
      netball specific movements.
AB  - OBJECTIVE: To investigate the effects of a prophylactic knee brace on knee joint
      kinetics and kinematics during netball specific movements. DESIGN: Repeated
      measures. SETTING: Laboratory. PARTICIPANTS: Twenty university first team level
      female netball players. OUTCOME MEASUREMENTS: Participants performed three
      movements, run, cut and vertical jump under two conditions (brace and no-brace).
      3-D knee joint kinetics and kinematics were measured using an eight-camera motion
      analysis system. Knee joint kinetics and kinematics were examined using 2 * 3
      repeated measures ANOVA whilst the subjective ratings of comfort and stability
      were investigated using chi-squared tests. RESULTS: The results showed no
      differences (p > 0.05) in knee joint kinetics. However the internal/external
      rotation range of motion was significantly (p < 0.05) reduced when wearing the
      brace in all movements. The subjective ratings of stability revealed that
      netballers felt that the knee brace improved knee stability in all movements.
      CONCLUSIONS: Further study is required to determine whether reductions in
      transverse plane knee range of motion serve to attenuate the risk from injury in
      netballers.

PMID- 27697388
TI  - A Comparison of Radial and Femoral Coronary Angiography in Patients From SNAPSHOT
      ACS, a Prospective Acute Coronary Syndrome Audit in Australia and New Zealand.
AB  - BACKGROUND: There is wide variation in the use of radial over femoral access for
      patients with ACS. This study evaluates the factors associated with the selection
      of radial versus femoral angiography in Australia and New Zealand and the effect
      of access site on clinical events in acute coronary syndrome (ACS) patients.
      METHODS: An analysis of the SNAPSHOT ACS audit was conducted during May 2012
      across 286 hospitals in Australia and New Zealand. Data collected included
      baseline patient characteristics, hospital site details, treatment received,
      clinical events in-hospital and mortality at 18 months. Univariate and
      multivariable analyses were performed. RESULTS: Of the 1621 patients undergoing
      coronary angiography, access was through the femoral artery in 1043 (63%), and
      the radial in 578 (36%) patients. Radial access dominated in New Zealand (241 out
      of 327, 73.7%), compared to Australia (337 out of 1293, 26.1%, p=<0.001), with
      interstate variation (6% to 54%, p=<0.001). Independent predictors of access site
      included country of admission (Odds of radial, Aus v NZ OR 0.14, 95% CI 0.08
      0.24, p=<0.0001), prior CABG surgery (OR 0.16, 95% CI 0.09-0.31, p=<0.0001), high
      GRACE score (90th decile) (OR 0.44, 95% CI 0.21-0.91, p=0.026) and admission to a
      centre with high annual PCI volume (>209 cases per year) (OR 1.86, 95% CI 1.06
      3.26, p=0.03). After adjustment, there was no difference in clinical events in
      hospital or mortality at 18 months CONCLUSION: Coronary angiography in New
      Zealand rather than Australia is the strongest predictor of radial access in ACS
      patients. There was no difference in outcomes according to access site in this
      population based cohort study.

PMID- 27697390
TI  - Zoonotic tuberculosis in human beings caused by Mycobacterium bovis-a call for
      action.
AB  - Mycobacterium tuberculosis is recognised as the primary cause of human
      tuberculosis worldwide. However, substantial evidence suggests that the burden of
      Mycobacterium bovis, the cause of bovine tuberculosis, might be underestimated in
      human beings as the cause of zoonotic tuberculosis. In 2013, results from a
      systematic review and meta-analysis of global zoonotic tuberculosis showed that
      the same challenges and concerns expressed 15 years ago remain valid. These
      challenges faced by people with zoonotic tuberculosis might not be proportional
      to the scientific attention and resources allocated in recent years to other
      diseases. The burden of zoonotic tuberculosis in people needs important
      reassessment, especially in areas where bovine tuberculosis is endemic and where
      people live in conditions that favour direct contact with infected animals or
      animal products. As countries move towards detecting the 3 million tuberculosis
      cases estimated to be missed annually, and in view of WHO's end TB strategy
      endorsed by the health authorities of WHO Member States in 2014 to achieve a
      world free of tuberculosis by 2035, we call on all tuberculosis stakeholders to
      act to accurately diagnose and treat tuberculosis caused by M bovis in human
      beings.

PMID- 27697391
TI  - Altered breathing pattern valuation relatively to dyspnea assessment and
      treatment for low back pain: Effects of clinical practice.

PMID- 27697392
TI  - Development of a new palpation method using alternative landmarks for the
      determination of thoracic transverse processes: An in vitro study.
AB  - Palpation methods (PMs) have been proposed to guide clinicians in locating the
      thoracic transverse processes (TTPs). However, no studies have assessed the
      validity of TTPs palpation or the added value of musculoskeletal ultrasound
      (MSU). The objectives of the present study were (1) to explore the validity of
      TTPs location using palpation as commonly performed by clinicians, (2) to develop
      an accurate and valid PM, and (3) to assess the added value of MSU. A
      standardized procedure was used on six cadavers. It consisted in the insertion of
      markers through the T3, T5, T6 and T8 TTPs and spinous processes, which were
      identified using palpation and MSU. First, a fresh cadaver was used to explore
      the validity of the common palpation method. Since poor validity was observed,
      one intermediate and a final PMs were tested on a total of five Thiel-embalmed
      specimens. A descriptive analysis was performed and agreement between MSU and the
      final PM was determined. The final PM led to the proper determination of all TTPs
      on three specimens with a mean error of 4 +/- 1.8 mm in relation to the TTPs
      center. The coefficient of variations and root mean square errors were <=0.15 and
      0.21 mm, respectively. Bland-Altman plot showed no differences between palpation
      and MSU. In conclusion, this study reports the validity of a new PM using
      multiple landmarks to guide TTPs determination and for which MSU does not seem to
      add value in accuracy. These results may have important clinical implications for
      clinicians using palpation.

PMID- 27697393
TI  - [The Paris Manifesto: It's time for new male contraceptives].

PMID- 27697394
TI  - Review on crosstalk and common mechanisms of endocrine disruptors: Scaffolding to
      improve PBPK/PD model of EDC mixture.
AB  - Endocrine disruptor compounds (EDCs) are environment chemicals that cause harmful
      effects through multiple mechanisms, interfering with hormone system resulting in
      alteration of homeostasis, reproduction and developmental effect. Many of these
      EDCs have concurrent exposure with crosstalk and common mechanisms which may lead
      to dynamic interactions. To carry out risk assessment of EDCs' mixture, it is
      important to know the detailed toxic pathway, crosstalk of receptor and other
      factors like critical window of exposure. In this review, we summarize the major
      mechanism of actions of EDCs with the different/same target organs interfering
      with the same/different class of hormone by altering their synthesis, metabolism,
      binding and cellular action. To show the impact of EDCs on life stage
      development, a case study on female fertility affecting germ cell is illustrated.
      Based on this summarized discussion, major groups of EDCs are classified based on
      their target organ, mode of action and potential risk. Finally, a conceptual
      model of pharmacodynamic interaction is proposed to integrate the crosstalk and
      common mechanisms that modulate estrogen into the predictive mixture dosimetry
      model with dynamic interaction of mixture. This review will provide new insight
      for EDCs' risk assessment and can be used to develop next generation PBPK/PD
      models for EDCs' mixture analysis.

PMID- 27697395
TI  - Correlation of the predictive ability of early warning metrics and mortality for
      cardiac arrest patients receiving in-hospital Advanced Cardiovascular Life
      Support.
AB  - BACKGROUND: The Modified Early Warning Score (MEWS) helps identify patients
      experiencing a decline in physiological parameters that indicate risk for cardiac
      arrest (CA). OBJECTIVES: To assess the association between MEWS values and
      patient survival following in-hospital CA. METHODS: Retrospective cohort study of
      patients who experienced in-hospital CA. The relationship between CA survival and
      MEWS values as well as other risk factors such as age, gender and type of
      electrographic cardiac rhythms was analyzed using logistic regression. RESULTS:
      Survival rate to hospital discharge was 21%. Strong predictors for survival were
      MEWS values at hospital admission (p < .002), younger age (p < .005), ventricular
      fibrillation (p < .0001), and ventricular tachycardia (p < .0001). Gender and
      MEWS 4 hours prior to CA were not significantly associated with survival.
      CONCLUSIONS: Survival following CA was significantly associated with MEWS at
      hospital admission but not 4 hours prior to CA. The type of cardiac rhythm and
      age were also predictive of survival.

PMID- 27697396
TI  - Pediatric and neonatal transport in Spain, Portugal and Latin America.
AB  - OBJECTIVE: To study the organization of inter-hospital transport of pediatric and
      neonatal patients in Spain, Portugal and Latin America. DESIGN: An observational
      study was performed. An on-line survey was sent by email including questions
      about characteristics of national, regional and local health transport systems,
      vehicles, material, and composition of the transport team and their training.
      SETTING: Hospital pediatric healthcare professionals treating children in Spain,
      Portugal and Latin America RESULTS: A total of 117 surveys from 15 countries were
      analyzed. Of them, 55 (47%) come from 15 regions of Spain and the rest from
      Portugal and 13 Latin American countries. The inter-hospital transport of
      pediatric patients is unified only in the Spanish regions of Baleares and
      Cataluna and in Portugal. Chile has a mixed unified transport system for
      pediatric and adult patients. Only 51.4% of responders have an educational
      program for the transport personnel, and only in 36.4% of them the educational
      program is specific for pediatric patients. In Spain and Portugal the transport
      is executed mostly by public entities, while in Latin America public and private
      systems coexist. Specific pediatric equipment is more frequent in the transport
      teams in the Iberian Peninsula than in Latin American teams. The specific
      pediatric transport training is less frequent for teams in Latin America than on
      Spain and Portugal. CONCLUSIONS: There is a great variation in the organization
      of children transport in each country and region. Most of countries and cities do
      not have unified and specific teams of pediatric transport, with pediatric
      qualified personnel and specific material.

PMID- 27697397
TI  - Implants in free fibula flap supporting dental rehabilitation - Implant and peri
      implant related outcomes of a randomized clinical trial.
AB  - OBJECTIVES: The objective of this study was to assess the difference in success
      rates of implants when using two or four implant-supported-overdentures following
      segmental mandibular reconstruction with fibula free flap. METHODS AND DESIGNS:
      This prospective, parallel designed, randomized clinical study was conducted with
      1:1 ratio. At baseline, all participants already had segmental reconstruction of
      mandible with free fibula flap. The participants were randomized into two groups:
      Group-I received implant-supported-overdentures on two tissue-level implants and
      Group-II received implant-supported-overdentures on four tissue-level implants.
      Success rates of the implants were evaluated at 3 months, 6 months and 12 months
      following implant loading using marginal bone level changes as well as peri
      implant indices (Buser et al., 1990). RESULTS: 52 patients were randomized into
      two treatment groups (26 each), out of which 18 patients (36 implants) of Group-I
      and 17 patients (68 implants) of Group-II were evaluated. One implant in Group-I
      was lost due to infective complications and one patient in the same group had
      superior barrel necrosis. There was a statistically significant increase at both
      time points (p = 0.03, p = 0.04 at 6 months, 12 months) in the amount of marginal
      bone loss in Group-I (0.4 mm, 0.5 mm at 6 months, 12 months) as compared to Group
      II (0.1 mm, 0.2 mm at 6 months, 12 months). There were no clinically significant
      changes peri-implant parameters between both groups. Peri-implant soft tissue
      hyperplasia was seen in both groups, 32% of implants at 3-months, 26% at 6-months
      and 3% at 12-months follow-up. CONCLUSION: The results of this study show that
      patients with 2-implant-supported-overdentures had higher marginal bone loss as
      compared to patients with 4-implant-supported-overdentures. There were no
      clinically significant differences in peri-implant soft tissue factors in
      patients with 2- or 4-implant-supported-overdentures. Hyperplastic peri-implant
      tissues are common in the early implant-loading phase and tend to decrease over
      time under appropriate management.

PMID- 27697398
TI  - Reconstruction of the maxilla following hemimaxillectomy defects with scapular
      tip grafts and dental implants.
AB  - BACKGROUND: Treatment of post-resective defects of the maxilla can be challenging
      and usually requires dental obturation or microvascular reconstruction. As
      compared to soft-tissue microvascular grafts, bone reconstruction can
      additionally allow for facial support and retention of dental implants. The aim
      of this study was to evaluate scapular tip grafts with respect to their
      applicability for maxillary reconstruction and their potential to retain dental
      implants for later dental rehabilitation. MATERIALS AND METHODS: In this
      retrospective study, 14 patients with hemimaxillectomy defects were reconstructed
      with free scapular tip grafts, oriented horizontally, to rebuild the palate and
      alveolar ridge. After bone healing, three-dimensional virtual implant planning
      was performed, and a radiographic guide was fabricated to enable implant
      placement in the optimal anatomic and prosthetic position. All patients'
      mastication and speech were evaluated, along with the extent of defect closure,
      suitability of the graft sites for implant placement, and soft-tissue stability.
      Pre- and postsurgical radiographs were also evaluated. RESULTS: A good
      postoperative outcome was achieved in all patients, with complete closure of
      maxillary defects that were class II, according to the system of Brown and Shaw.
      Additional bone augmentation was necessary in two patients in order to increase
      vertical bone height. Patients were subsequently treated with 50 dental implants
      to retain dental prostheses. In all cases, additional soft-tissue surgery was
      necessary to achieve a long-term stable periimplant situation. No implants were
      lost during the mean observation period of 34 months. CONCLUSIONS: Due to its
      specific form, the scapular tip graft is well suited to reconstruct the palate
      and maxillary alveolar ridge and to enable subsequent implant-retained
      rehabilitation. Due to the limited bone volume, an accurate three-dimensional
      graft orientation is essential. Furthermore, most cases require additional soft
      tissue surgery to achieve a long-term stable periimplant situation.

PMID- 27697399
TI  - Osseointegration and implant stability of extraoral implants in Gottingen
      minipigs after irradiation.
AB  - OBJECTIVES: The aim of this study was to compare the influence of implant surface
      treatment and irradiation dose on implant stability and osseointegration of 144
      extraoral implants in irradiated frontal bone of minipigs. MATERIAL AND METHODS:
      144 implants with 3 different surface treatments (machined, etched and HAVD
      coated) were implanted in the frontal bone of 16 Gottingen minipigs. Three groups
      of four pigs received radiation with equivalent doses of 25, 50 and 70 Gy, and
      one group served as control. Resonance frequency analysis (RFA) was performed
      recording Implant Stability Quotients (ISQ) at implant placement and 3 months
      thereafter. Removal torque was measured whilst removing specific implants after 3
      months. In addition, the bone-to-implant contact (BIC) was analyzed. RESULTS:
      Evaluation of ISQ, BIC-values showed no significant difference between the
      different surface treatments in irradiated and non-irradiated bone. Removal
      torque revealed statistically significant differences between machined and HAVD
      coated implants in the irradiated bone. CONCLUSIONS: Implant stability and
      osseointegration, based on Removal Torque showed significant higher results for
      the HAVD-coated implants. No significant difference was observed between the
      irradiated and non-irradiated animals. This study shows that HAVD-coated
      extraoral implants can potentially be used for craniofacial rehabilitation in non
      irradiated and irradiated bone.

PMID- 27697400
TI  - Lack of effectiveness of antibiotics in chronic low back pain with Modic 1
      changes.

PMID- 27697401
TI  - High prevalence of dementia in women with osteoporosis.
AB  - INTRODUCTION: Alzheimer's disease or other Dementias (ADD) and postmenopausal
      osteoporosis are two major public health problems with a huge impact on
      mortality. Here, we examined the prevalence of ADD in postmenopausal women with
      osteoporosis, monitored within a dedicated fracture liaison service. METHODS: We
      conducted a cross-sectional observational study in a population of 2041 women,
      visiting the university hospital of Saint-Etienne for a peripheral fragility
      fracture. We assessed the prevalence of ADD among these patients and compared to
      French population. We also compared the characteristics of women with ADD and
      without ADD. RESULTS: ADD prevalence was on average 13.5% in the population of
      interest with a mean age of 85years. As women with ADD were older than women
      without ADD, the prevalence of the disease significantly increased with age as
      0%, 1.8%, 13% and 29.7% in<55, 55-74, 75-79 and 85-89years old groups,
      respectively. Proximal femoral fracture was the most frequent fracture (77%)
      followed by wrist fracture (13%), and then proximal humerus fracture (10%). ADD
      prevalence observed in our study was 3 to 4 times the ADD prevalence in France.
      Despite the overall increase of the ADD prevalence with age, it was still 2.2 and
      1.9 times that of the French female population in the 80-84 and 85-89 age groups
      respectively. CONCLUSION: ADD prevalence was higher in postmenopausal women with
      severe osteoporosis, especially those with femoral fractures. Thus, our results
      incite to a more efficient care of this population with a high risk of fracture
      and mortality.

PMID- 27697402
TI  - The posterior-based buccinator myomucosal flap (Bozola's flap).
AB  - Based on a case of reconstruction after oncologic resection of the hard palate,
      the authors document the key technical points for harvesting a posterior-based
      buccinator myomucosal flap (Bozola's flap), and its limitations and indications
      after oncologic resection of tumors originating from the oral cavity
      and/oropharynx.

PMID- 27697403
TI  - The helicopter as a caring context: Experiences of people suffering trauma.
AB  - INTRODUCTION: When emergency medical services (EMS) are needed, the choice of
      transport depends on several factors. These may include the patient's medical
      condition, transport accessibility to the accident site and the receiving
      hospital's resources. Emergency care research is advancing, but little is known
      about the patient's perspective of helicopter emergency medical services (HEMS).
      AIM: The aim of this study was to describe trauma patients' experiences of HEMS.
      METHOD: Thirteen persons (ages 21-76) were interviewed using an interview guide.
      Data were analyzed using qualitative content analysis. FINDINGS: The analysis
      resulted in three themes: Being distraught and dazed by the event - patients
      experienced shock and tension, as well as feelings of curiosity and excitement.
      Being comforted by the caregivers - as the caregivers were present and attentive,
      they had no need for relatives in the helicopter. Being safe in a restricted
      environment - the participants' injuries were taken seriously and the caregivers
      displayed effective teamwork. CONCLUSION: For trauma patients to be taken
      seriously and treated as 'worst cases' enables them to trust their caregivers and
      'hand themselves over' to their care. HEMS provide additional advantageous
      circumstances, such as being the sole patient and having proximity to a small,
      professional team.

PMID- 27697404
TI  - Comparison of Canadian and Swiss Surgical Training Curricula: Moving on Toward
      Competency-Based Surgical Education.
AB  - OBJECTIVE: Quality of surgical training in the era of resident duty-hour
      restrictions (RDHR) is part of an ongoing debate. Most training elements are
      provided during surgical service. As exposure to surgical procedures is important
      but time-consuming, RDHR may affect quality of surgical training. Providing
      structured training elements may help to compensate for this shortcoming. DESIGN:
      This binational anonymous questionnaire-based study evaluates frequency, time,
      and structure of surgical training programs at 2 typical academic teaching
      hospitals with different RDHR. SETTING: Departments of Surgery of University of
      Basel (Basel, Switzerland) and the Queen's University (Kingston, Ontario,
      Canada). PARTICIPANTS: Surgical consultants and residents of the Queen's
      University Hospital (Kingston, Ontario, Canada) and the University Hospital Basel
      (Basel, Switzerland) were eligible for this study. RESULTS: Questionnaire
      response rate was 37% (105/284). Queen's residents work 80 hours per week,
      receiving 7 hours of formal training (8.8% of workweek). Basel residents work 60
      hours per week, including 1 hour of formal training (1.7% of working time).
      Queen's faculty and residents rated their program as "structured" or "rather
      structured" in contrast to Basel faculty and residents who rated their programs
      as "neutral" in structure or "unstructured." Respondents identified specific
      structured training elements more frequently at Queen's than in Basel. Two-thirds
      of residents responded that they seek out additional surgical experiences through
      voluntary extra work. Basel participants articulated a stronger need for
      improvement of current surgical training. Although Basel residents and
      consultants in both institutions fear negative influence of RDHR on the training
      program, this was not the case in Queen's residents. CONCLUSIONS: Providing more
      structured surgical training elements may be advantageous in providing optimal
      quality surgical education in an era of work-hour restrictions.

PMID- 27697405
TI  - Total hip replacement in young non-ambulatory cerebral palsy patients.
AB  - INTRODUCTION: The everyday life of a non-ambulatory adolescent or young adult
      with cerebral palsy can be severely impaired by a painful or stiff hip. The usual
      surgical solutions such as proximal femoral resection (PFR) are not entirely
      satisfactory for pain relief, and are mutilating. HYPOTHESIS: A retrospective
      study assessed the impact of total hip replacement (THR) on such impairment, on
      the hypothesis that it is more effective than PFR in relieving pain, without
      aggravating disability. PATIENTS AND METHODS: The surgical technique consisted in
      implanting a dual-mobility prosthesis with uncemented acetabular component and
      cemented femur, after upper femoral shaft shortening and short hip-spica cast
      immobilization. Forty THRs were performed in 33 patients, including 31 with
      multiple disability. Follow-up assessment focused on change in functional status,
      pain, and range of motion. RESULTS: Mean follow-up was 5 years. Pain was more or
      less entirely resolved. Improvement in range of motion was less striking, and
      there was no significant change in functional status. There were 2 general, 2
      septic and 10 mechanical complications, 6 of which required surgical revision.
      DISCUSSION: In non-ambulatory cerebral palsy, THR provided much better
      alleviation of pain than found with PFR treatment. It should be reserved for
      patients able to withstand fairly long surgery and with femur size compatible
      with implantation of a femoral component, however small. LEVEL OF EVIDENCE: IV,
      retrospective study.

PMID- 27697406
TI  - Diagnostic value of ultrasonography in elbow trauma in children: Prospective
      study of 34 cases.
AB  - INTRODUCTION: Among the various elbow injuries in children that initially have
      normal radiographs, a certain number of occult fractures are only diagnosed
      correctly after the fact, during a follow-up visit. PURPOSE: This study evaluated
      the diagnostic contribution of ultrasonography in the treatment of acute elbow
      injuries in children and the strategic and economic impact of using this tool
      alongside radiography. MATERIALS AND METHODS: During this prospective study
      performed between January 1 and April 1 2014, elbow ultrasonography was performed
      within 6 days in all children under 15 years of age with a suspected occult
      fracture. The ultrasonography exam looked for lipohemarthrosis, the posterior fat
      pad sign and cortical disruption. If no fracture was visible on ultrasonography,
      a removable splint was given to the patient to relieve pain, and no radiological
      or clinical follow-up was scheduled. The patients were contacted again at least
      15 days later to determine whether an undetected fracture was present. Lastly, we
      evaluated the cost of treatment with and without ultrasonography in the cases
      where no fracture was diagnosed. RESULTS: In 13 cases, ultrasonography revealed
      lipohemarthrosis and a fat pat sign, with cortical disruption also present in 11
      of these cases. In two cases, the diagnosis was made based solely on the presence
      of lipohemarthrosis and a fat pat sign. There were seven lateral condyle
      fractures, two medial epicondyle fractures and two supracondylar fractures. Among
      the 21 patients with normal ultrasonography, no fracture was diagnosed later on.
      In patients without a fracture, using ultrasonography resulted in a cost savings
      of ?29.10 per patient versus not using it. CONCLUSION: In our study,
      ultrasonography is a sensitive examination for the diagnosis of occult elbow
      fractures in children. When the radiography and ultrasonography are both normal,
      the possibility of fracture can be rule out definitively, which reduces the need
      for immobilization, follow-up and treatment costs. The findings of this
      preliminary study should be validated with a larger prospective study.

PMID- 27697407
TI  - Utility of prognostic scoring systems in management of hepatocellular carcinoma.

PMID- 27697408
TI  - Response to Letter to the Editor: Vitamin D status may help explain racial
      disparities in breast cancer hospitalization outcomes.

PMID- 27697410
TI  - Time Dependence of Radiation-induced Hypothalamic-Pituitary Axis Dysfunction in
      Adults Treated for Non-pituitary, Intracranial Neoplasms.
AB  - AIMS: Hypothalamic-pituitary axis (HPA) dysfunction is a sequela of cranial
      radiotherapy. The purpose of this study was to use endocrine data from existing
      publications to characterise the baseline endocrine status, the effects of
      radiotherapy on the HPA during the first follow-up year and the time dependence
      of radiation-induced HPA dysfunction in patients treated with radiotherapy for
      non-pituitary intracranial neoplasms. MATERIALS AND METHODS: A systematic search
      of databases was carried out for articles that reported the results of endocrine
      testing for patients aged 16 years and older who were treated with neurosurgery
      for non-pituitary intracranial neoplasms or radiotherapy for nasopharyngeal
      neoplasms. To analyse the radiotherapy-related changes in hormone levels over
      time, long-term prospective endocrine data from nasopharyngeal studies were
      normalised to baseline hormone data and fitted to an exponential decay model.
      This process was repeated with normalisation to year 1 hormone data. RESULTS:
      Eight unique articles met eligibility criteria. HPA dysfunction occurred in 21.6
      64.7% of patients who were assessed for endocrinopathies following neurosurgery.
      Studies on the early effects of radiotherapy on nasopharyngeal patients showed
      statistically significant changes in growth hormone, luteinizing hormone and
      follicle stimulating hormone levels during the first year of follow-up. Time
      dependence modelling showed that normalisation to year 1 hormone levels yield
      exponential equations with stronger measures of goodness of fit. CONCLUSION: HPA
      dysfunction in patients treated for non-pituitary intracranial neoplasms is
      probably a result of both neurosurgery and radiotherapy treatments. Although
      statistically significant endocrine changes can occur during this first year of
      follow-up, those documented at year 1 may be more predictive of subsequent HPA
      dysfunction.

PMID- 27697409
TI  - The Ability of Patient-Symptom Questionnaires to Differentiate PVFMD From Asthma.
AB  - OBJECTIVES: Goals of the current study were to (1) conduct initial validation of
      a new Paradoxical Vocal Fold Movement Disorder Screening Questionnaire (PVFMD
      SQ); (2) determine if symptom-based questionnaires can discriminate between
      patients with confirmed PVFMD and those with diagnosed uncontrolled asthma
      without clinical suspicion for PVFMD; and (3) determine if a new questionnaire
      with diagnostic specificity could be created from a combination of significant
      items on previously validated questionnaires. METHODS: This is a prospective,
      case-controlled study of patients with PVFMD only and asthma only, who completed
      five questionnaires: Dyspnea Index, Reflux Symptom Index, Voice Handicap Index
      10, Sino-Nasal Questionnaire, and PVFMD-SQ. Factor analysis was completed on the
      new PVFMD-SQ, and the discrimination ability of selected factors was assessed by
      receiver operating characteristics curve. The factor with the greatest
      discriminatory ability was selected to create one diagnostic questionnaire, and
      scores for each participant were calculated to estimate how well the factor
      correlated with a PVFMD or asthma diagnosis. Mean scores on all questionnaires
      were compared to test their discriminatory ability. RESULTS: Patients with PVFMD
      showed greater voice handicap and reflux symptoms than patients with asthma. A 15
      item one-factor questionnaire was developed from the original PVFMD-SQ, with a
      sensitivity of 89% and specificity of 73% for diagnosing asthma versus PVFMD. The
      combined questionnaires resulted in four factors, none of which showed
      discriminatory ability between PVFMD and asthma. CONCLUSION: This study
      represents the first time that a patient symptom-based screening tool has shown
      diagnostic sensitivity to differentiate PVFMD from asthma in a cohort of
      symptomatic patients.

PMID- 27697411
TI  - Management of Early-stage Hodgkin Lymphoma: A Practice Guideline.
AB  - In the past, treatment for patients with early-stage Hodgkin lymphoma consisted
      mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are
      treatment options. These guidelines aim to provide recommendations on the optimal
      management of early-stage Hodgkin lymphoma. We conducted a systematic review
      searching MEDLINE, EMBASE, the Cochrane Library and other literature sources from
      2003 to 2015, and applied the Grading of Recommendations Assessment, Development
      and Evaluation (GRADE). Two authors independently reviewed and selected studies,
      and appraised the evidence quality. The document underwent internal and external
      review by content, methodology experts, a patient representative and clinicians
      in Ontario. We have issued recommendations for patients with classical Hodgkin
      lymphoma and with nodular lymphocyte predominant Hodgkin lymphoma; with
      favourable and unfavourable prognosis; and for the use of positron emission
      tomography to direct treatment. We have provided our interpretation of the
      evidence and considerations for implementation. Examples of recommendations are:
      'Patients with early-stage classical Hodgkin lymphoma should not be treated with
      radiotherapy alone'; 'chemotherapy plus radiotherapy or chemotherapy alone are
      recommended treatment options for patients with early-stage non-bulky Hodgkin
      lymphoma'; 'The Working Group does not recommend the use of a negative interim
      positron emission tomography scan alone to identify patients with early-stage
      Hodgkin lymphoma for whom radiotherapy can be omitted without a reduction in
      progression-free survival'. Through the use of GRADE, recommendations were geared
      towards patient important outcomes and their strength reflected the available
      evidence and its interpretation from the patients' point of view.

PMID- 27697412
TI  - Severe Parkinsonism with respiratory failure in peritoneal dialysis patient.

PMID- 27697413
TI  - Plant phosphates, phytate and pathological calcifications in chronic kidney
      disease.
AB  - Phytate, or myo-inositol 1,2,3,4,5,6-hexakis dihydrogen phosphate (InsP6), is a
      naturally occurring phosphorus compound that is present in many foods, mainly
      legumes, whole grains and nuts. Patients with chronic kidney disease (CKD) have
      cardiovascular disease mortality up to 30times higher than the general
      population. Vascular calcifications (VCs) directly contribute to overall
      morbidity and mortality, especially in CKD. In part, this high mortality is due
      to elevated levels of phosphorus in the blood. Therefore, control of dietary
      phosphorus is essential. Dietary phosphorus can be classified according to its
      structure in organic phosphorus (plant and animal) and inorganic (preservatives
      and additives). Plant-phosphorus (legumes and nuts), mainly associated with
      InsP6, is less absorbable by the human gastrointestinal tract as the
      bioavailability of phosphorous from plant-derived foods is very low. Recent data
      indicate that restriction of foods containing plant phosphates may compromise the
      adequate supply of nutrients that have a beneficial effect in preventing
      cardiovascular events, such as InsP6 or fibre found in legumes and nuts.
      Experimental studies in animals and observational studies in humans suggest that
      InsP6 can prevent lithiasis and VCs and protect from osteoporosis. In conclusion,
      we need prospective studies to elucidate the potential benefits and risks of
      phytate (InsP6) through the diet and as an intravenous drug in patients on
      haemodialysis.

PMID- 27697414
TI  - Delphi consensus on the diagnosis and management of dyslipidaemia in chronic
      kidney disease patients: A post hoc analysis of the DIANA study.
AB  - BACKGROUND AND OBJECTIVES: This post hoc study analysed the perception of the
      relevance of chronic kidney disease (CKD) in dyslipidaemia screening and the
      choice of statin among primary care physicians (PCPs) and other specialists
      through a Delphi questionnaire. METHODS: The questionnaire included 4blocks of
      questions concerning dyslipidaemic patients with impaired carbohydrate
      metabolism. This study presents the results of the impact of CKD on screening and
      the choice of statin. RESULTS: Of the 497 experts included, 58% were PCPs and 42%
      were specialists (35, 7% were nephrologists). There was consensus by both PCPs
      and specialists, with no difference between PCPs and specialists, that CKD
      patients should undergo a dyslipidaemia screening and that the screening should
      be part of routine clinical practice. However, there was no consensus in
      considering the estimated glomerular filtration rate (eGFR) (although there was
      consensus among PCPs and nephrologists), or considering albuminuria when
      selecting a statin, or in determining albuminuria during follow-up after having
      initiated treatment with statins (although there was consensus among the
      nephrologists). CONCLUSIONS: The consensus to analyse the lipid profile in CKD
      patients suggests acknowledgment of the high cardiovascular risk of this
      condition. However, the lack of consensus in considering renal function or
      albuminuria, both when selecting a statin and during follow-up, suggests a
      limited knowledge of the differences between statins in relation to CKD. Thus, it
      would be advisable to develop a guideline/consensus document on the use of
      statins in CKD.

PMID- 27697415
TI  - Use of suborbicularis oculi fat flap to cover peri-orbital bone exposure.
AB  - Wide resection of recurrent basal cell carcinoma (BCC) in the peri-orbital
      infraorbital-nasal area may include periosteum resection with maxillary or nasal
      bone exposure. The absence of vascularized periosteum makes the defect
      ungraftable and local flaps are often required. As an alternative to a large
      single flap or a combination of flaps, it is possible to turn the ungraftable
      portion of the defect into a graftable one. The suborbicularis oculi fat (SOOF)
      flap is an advancement flap that is used in aesthetic surgery for midface
      rejuvenation. The use of the SOOF flap along with a full-thickness skin graft, as
      an alternative to the use of other standardized flaps to cover defects in the
      peri-orbital-infraorbital-nasal area with avascularized tissue or noble structure
      exposure, is reported herein. As an immediate single-stage reconstruction, this
      procedure leaves other flap options intact in the event of re-operation for a
      recurrent tumour.

PMID- 27697416
TI  - Lipid - Motor Interactions: Soap Opera or Symphony?
AB  - Intracellular transport of organelles can be driven by multiple motor proteins
      that bind to the lipid membrane of the organelle and work as a team. We review
      present knowledge on how lipids orchestrate the recruitment of motors to a
      membrane. Looking beyond recruitment, we also discuss how heterogeneity and local
      mechanical properties of the membrane may influence function of motor-teams.
      These issues gain importance because phagocytosed pathogens use lipid-centric
      strategies to manipulate motors and survive in host cells.

PMID- 27697417
TI  - Implementation of the French national consensus for the management of ulcerative
      colitis into clinical practice.
AB  - BACKGROUND: Recently, treatment algorithms were developed in France additionally
      to ECCO recommendations that should be used as reference for ulcerative colitis
      (UC) management. Nevertheless, their implementation in clinical practice remains
      challenging. AIMS: To evaluate the prevalence of the use of these UC management
      algorithms in 127 patients followed by private gastroenterologists. METHODS:
      Charts of all UC patients seen during the year 2015 (n=127) by 10
      gastroenterologists were reviewed. The gastroenterologist's management was then
      compared to the corresponding algorithm situation and, in case of disagreement,
      analysed by an expert committee. RESULTS: 94.5% of patients corresponded to a
      clinical situation described in algorithms. Gastroenterologist's management was
      adequate to the corresponding algorithm situation in 74.2% of cases. Among the 31
      cases of disagreement, the gastroenterologist's decision differed from the
      algorithm position in 21 cases, and in 76.2% of cases the expert committee would
      have made the same decision. In the remaining 10 cases, the decision differed
      from the corresponding algorithm for reasons independent from the
      gastroenterologist (patient's choice etc.). CONCLUSIONS: French national
      algorithms for UC management allowed coverage of 95% of clinical cases in real
      world. In three quarters of cases, these algorithms were strictly followed by
      private gastroenterologists. Dissemination of these algorithms could optimize and
      strengthen the practitioner's choice.

PMID- 27697418
TI  - Skeletal muscle metastases as the first sign of a recurrence of gastric
      carcinoma.

PMID- 27697419
TI  - Nonalcoholic fatty liver disease is associated with coronary artery
      calcification: A systematic review and meta-analysis.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated increased
      cardiovascular events and mortality. Coronary artery calcium scanning (CAC) is
      the robust predictor of coronary events in the asymptomatic individuals. Several
      recent studies have investigated the association between NAFLD and this surrogate
      marker. Thus, we conducted a systematic review and meta-analysis to better
      characterize the association between NAFLD and CAC. METHODS: MEDLINE and EMBASE
      were searched through May 2016. Primary outcome was the association between NAFLD
      and CAC. Pooled odds ratio (OR) and 95% confidence interval (CI) from
      multivariable-adjusted estimates were calculated using a random-effects model.
      The between-study heterogeneity of effect-size was quantified using the Q
      statistic and I2. RESULTS: Data were extracted from 16 studies (all cross
      sectional studies) involving 16,433 NAFLD patients and 41,717 controls. NAFLD is
      significantly associated with CAC score >0 and CAC score >100 with pooled OR of
      1.41 (95%CI 1.26-1.57, Pheterogeneity=0.07, I2=66%) and 1.24 (95%CI 1.02-1.52,
      Pheterogeneity=0.10, I2=42%). CONCLUSIONS: NAFLD is associated with increased
      coronary artery calcification independent of traditional risk factors. The
      assessment of coronary artery calcium may be useful in identifying NAFLD patients
      at risk of future cardiovascular events.

PMID- 27697421
TI  - Carcinosarcoma of the Breast: An Aggressive Subtype of Metaplastic Cancer. Report
      of a Rare Case in a Young BRCA-1 Mutated Woman.

PMID- 27697423
TI  - A problem unstuck? Evaluating the effectiveness of sticker prompts for
      encouraging household food waste recycling behaviour.
AB  - This Randomised Control Trial (RCT) investigated the effectiveness of using
      stickers as a visual prompt to encourage the separate collection of household
      food waste for recycling in two local authorities in South East England. During a
      baseline period of up to 15weeks, separately collected food waste was weighed (in
      tonnes) and averaged across households in both treatment (N=33,716 households
      within 29 defined areas) and control groups (N=30,568 households within 26
      areas). A sticker prompt was then affixed to the lids of refuse bins in the
      treatment group area only. Weights for both groups were subsequently measured
      across a 16-week experimental period. Results showed that, in the control group,
      there was no change in the average weight of food waste captured for recycling
      between the baseline and experimental period. However, there was a significant
      increase (20.74%) in the treatment group, and this change in behaviour persisted
      in the longer term. Sticker prompts therefore appear to have a significant and
      sustained impact on food waste recycling rates, while being simple, practically
      feasible and inexpensive (L0.35 per household) for local authorities to implement
      at scale.

PMID- 27697422
TI  - Decrease of versican levels in the follicular dermal papilla is a remarkable
      aging-associated change of human hair follicles.

PMID- 27697424
TI  - Green and facile method for the recovery of spent Lithium Nickel Manganese Cobalt
      Oxide (NMC) based Lithium ion batteries.
AB  - The research reports a novel green method to use citrus fruits for the management
      of spent NMC based lithium ion batteries (LIBs). Citrus fruit juice (CJ) can
      provide an excellent chemical combination to remove the binder and support the
      leaching with efficiency in between 94% to 100%. CJ have many advantages in LIBs
      recycling as an economic and green method due to rich in many organic acids like
      citric and malic acid as complexing agents with ascorbic acid and citrus
      flavonoids, for the reduction of many heavy metals. Application of CJ can avoid
      the use of N-Methylpyrrolidine, gamma-Butyrolactone, dimethylformamide, and
      dimethyl sulfoxide like toxic solvents commonly used for peeling off Al/Cu.
      Furthermore, counterions (like Na+, Mg+, Ca2+) present in CJ was responsible for
      the improvement in the leaching efficiency of organic acids. A mechanistic
      pattern of the overall reaction was also proposed and duly supported by various
      spectroscopic techniques. Binder removal experiment was supported by analytical
      techniques like XRD, XRF, IR, and FE-SEM, while the metal concentration was
      monitored by using ICP-MS analysis.

PMID- 27697425
TI  - A Three-in-one Snapshot of the Modern Management of Heart Failure.

PMID- 27697426
TI  - Prevalence of thoracic diffuse idiopathic skeletal hyperostosis (DISH) in
      Japanese: Results of chest CT-based cross-sectional study.
AB  - BACKGROUND: The epidemiology and etiology of diffuse idiopathic skeletal
      hyperostosis (DISH) remain obscure. To date, to the best of our knowledge, there
      is no study that precisely evaluated the prevalence of thoracic DISH based on
      computed tomography (CT) data in large number of non-operated cohort with wide
      age distribution. METHODS: The participants of this study were the consecutive
      patients who have undergone chest CT for the examination of pulmonary diseases in
      our institute. The patients with previous thoracic spine surgery and younger than
      15 years old were excluded. Chest CT data were reconstructed in the condition
      suitable for bone evaluation by the software application. Definitive diagnosis of
      DISH was determined according to the criteria established by Resnick and
      Niwayama. Prevalence and distribution of thoracic DISH were reviewed and the data
      was statistically analyzed. RESULTS: Total 3013 patients (1261 females and 1752
      males) with the mean age of 65 years were recruited. The CT-based evidence of
      thoracic DISH was noted in 261 individuals (31 females and 230 males) (8.7%), and
      their mean age was 73 years. Statistical analyses revealed that thoracic DISH had
      a significant male preponderance. The mean age of thoracic DISH positive
      individuals was significantly higher than that of thoracic DISH negative
      individuals. There was significant difference of bone mass index (BMI) between
      thoracic DISH positive and negative individuals. Thoracic DISH was noted after
      the age of 40s with the highest distribution found at the age of 70s. No thoracic
      DISH localizes only higher thoracic region was found. CONCLUSIONS: The CT-based
      prevalence of thoracic DISH in Japanese was 8.7%. Thoracic DISH has a significant
      predisposition to elderly male with high BMI.

PMID- 27697427
TI  - The yolky thecoma.

PMID- 27697428
TI  - Impact of scorpion venom as an acute stressor on the neuroendocrine-immunological
      network.
AB  - Although immunomodulatory property and many other pharmaceutical applications of
      scorpion venom have been addressed before, no studies were reported about its
      application as a neuroimmunomodulator at therapeutic dose. In this study, we
      conceptualized the property of scorpion venom, capable of inducing the acute pain
      and neurotoxicity can cause acute stress resulting in the modulation of immune
      cells through HPA axis. The whole venom from Hottentotta rugiscutis, a widely
      seen scorpion in the region of eastern Karnataka, was extracted and injected a
      single dose of 1 mg/kg b.w. to Swiss albino mice and then erythrocytes and
      leukogram were measured. Whole brain AChE activity, corticosterone, cytokines and
      NO levels in plasma were also evaluated at various time points. Hrv didn't show
      any histopathological changes in the lymphoid organs and at the site of
      injection. However, lymphocytes and neutrophils did get altered at 2 h post
      injection. Plasma corticosterone, cytokine levels such as IL-1beta, IL-6, TNF
      alpha and IL-10 and the AChE activity were significantly increased in a time
      dependent manner. Based on these results, it may be predicted, Hrv's ability to
      cause acute stress resulted in the activation of HPA axis, which stimulates the
      release of glucocorticoid hormones which in turn elicits the immunomodulation of
      leukocytes by altering the levels of pro and anti-inflammatory cytokines. Thus,
      we can conclude, the impact of acute stress induced by Hrv can intercommunicate
      the signals between neuroendocrine-immune systems.

PMID- 27697429
TI  - Longer Versus Shorter Duration of Supervised Rehabilitation After Lung
      Transplantation: A Randomized Trial.
AB  - OBJECTIVE: To investigate the effects of a supervised longer- (14wk) versus
      shorter-duration (7wk) rehabilitation program after lung transplantation (LTX).
      DESIGN: Randomized controlled trial. SETTING: Outpatient rehabilitation gym
      setting. PARTICIPANTS: Post-LTX patients aged >=18 years (N=66; 33 women; mean
      age, 51+/-13y) who had undergone either single LTX or bilateral LTX.
      INTERVENTION: Outpatient rehabilitation program consisting of thrice-weekly
      sessions with cardiovascular training on bike ergometer and treadmill plus upper
      and lower limb strength training. MAIN OUTCOME MEASURES: Measures were taken at
      baseline, 7 weeks, 14 weeks, and 6 months by assessors who were blinded to group
      allocation. Functional exercise capacity was measured by the 6-minute walk test
      (6MWT). Strength of quadriceps and hamstrings was measured on an isokinetic
      dynamometer and recorded as average peak torque of 6 repetitions for both
      muscles. Quality of life (QOL) was assessed with the Medical Outcomes Study 36
      Item Short-Form Health Survey. RESULTS: Of the participants, 86% had bilateral
      LTX and 41% had primary diagnosis of chronic obstructive pulmonary disease. The
      6MWT increased in both groups with no significant difference between groups at
      any time point (mean 6mo 6MWD: short, 590+/-85m vs long, 568+/-127m; P=0.5).
      Similarly, at 6 months, there was no difference between groups in quadriceps
      average peak torque (mean, 115+/-38Nm vs 114+/-40Nm, respectively; P=.59),
      hamstring average peak torque (57+/-18Nm vs 52+/-19Nm, respectively; P=.36), or
      mental or physical health domains of quality of life. CONCLUSIONS: Shorter
      duration (7wk) of rehabilitation achieves comparable outcomes with 14 weeks of
      supervised rehabilitation for functional exercise capacity, lower limb strength,
      and quality of life at 6 months after LTX.

PMID- 27697431
TI  - NF-Y and SP transcription factors - New insights in a long-standing liaison.
AB  - For long it has been recognized that CCAAT boxes and GC-rich elements co-occur in
      many human and murine promoters within 100bp upstream of the transcription start
      site. The trimeric transcription factor NF-Y is the major CCAAT box-binding
      factor, and members of the SP family of transcription factors are the major GC
      box-binding proteins. Recent chromatin immunoprecipitations coupled with high
      throughput sequencing (ChIP-seq) have examined binding of NF-Y and the ubiquitous
      SP factors SP1, SP2 and SP3 genome-wide, allowing for comprehensive comparison of
      NF-Y and SP factor actions in the context of chromatin. Here, I attempt a
      synthesis of the earlier single-promoter type of analysis with the more recent
      genome-wide studies. In particular, I also discuss different modes of genomic
      interactions between SP factors and NF-Y that have emerged recently, and identify
      a key technical issue, which needs to be taken into account in a critical
      evaluation of genome-wide studies. This article is part of a Special Issue
      entitled: Nuclear Factor Y in Development and Disease, edited by Prof. Roberto
      Mantovani.

PMID- 27697430
TI  - Defining imaging biomarker cut points for brain aging and Alzheimer's disease.
AB  - INTRODUCTION: Our goal was to develop cut points for amyloid positron emission
      tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical
      thickness. METHODS: We examined five methods for determining cut points. RESULTS:
      The reliable worsening method produced a cut point only for amyloid PET. The
      specificity, sensitivity, and accuracy of cognitively impaired versus young
      clinically normal (CN) methods labeled the most people abnormal and all gave
      similar cut points for tau PET, FDG PET, and cortical thickness. Cut points
      defined using the accuracy of cognitively impaired versus age-matched CN method
      labeled fewer people abnormal. DISCUSSION: In the future, we will use a single
      cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19)
      based on the reliable worsening cut point method. We will base lenient cut points
      for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively
      impaired versus young CN method and base conservative cut points on the accuracy
      of cognitively impaired versus age-matched CN method.

PMID- 27697432
TI  - Antifungal activities of tacrolimus in combination with antifungal agents against
      fluconazole-susceptible and fluconazole-resistant Trichosporon asahii isolates.
AB  - The antifungal activity of tacrolimus in combination with antifungal agents
      against different fungal species has been previously reported. Here we report the
      in vitro interactions between tacrolimus and amphotericin B, fluconazole,
      itraconazole, and caspofungin against 30 clinical isolates of both fluconazole
      susceptible and fluconazole-resistant Trichosporon asahii. For these analyses, we
      used the broth microdilution method based on the M27-A3 technique and
      checkerboard microdilution method. Tacrolimus showed no activity against T.
      asahii strains (minimal inhibitory concentrations, MICs>64.0MUgmL-1). However, a
      larger synergistic interaction was observed by the combinations
      tacrolimus+amphotericin B (96.67%) and tacrolimus+caspofungin (73.33%) against
      fluconazole-susceptible isolates. Combinations with azole antifungal agents
      resulted in low rates of synergism for this group (fluconazole+tacrolimus=40% and
      itraconazole+tacrolimus=10%). Antagonistic interactions were not observed. For
      the fluconazole-resistant T. asahii group, all tested combinations showed
      indifferent interactions. The synergism showed against fluconazole-susceptible T.
      asahii isolates suggests that the potential antifungal activity of tacrolimus
      deserves in vivo experimental investigation, notably, the combination of
      tacrolimus with amphotericin B or caspofungin.

PMID- 27697433
TI  - Increased levels of soluble triggering receptor expressed on myeloid cells-1 in
      cerebrospinal fluid of subarachnoid hemorrhage patients.
AB  - Triggering receptor expressed on myeloid cells-1 (TREM-1) has been highlighted as
      a key amplifier of inflammatory response in various diseases. To determine the
      contribution of TREM-1 in the inflammatory cascade after subarachnoid hemorrhage
      (SAH), concentrations of soluble TREM-1 (sTREM-1) in cerebrospinal fluid (CSF)
      from 30 SAH patients and 9 healthy volunteers were measured by enzyme-linked
      immunosorbent assay. It was shown that the CSF sTREM-1 levels of SAH patients
      increased significantly than that of the volunteers (P<0.05). Interestingly, the
      levels were up-regulated dynamically over time with an early increase within
      2days and a late peak at day 6 after SAH onset. In addition, it was found that
      the early sTREM-1 levels (within 3days post-SAH) were negatively correlated with
      Glasgow Coma Scale (r=-0.550, P=0.022) and positively correlated with the Hunt
      and Hess scale (r=0.603, P=0.010) respectively conducted on admission, also the
      early sTREM-1 levels were negatively correlated with Glasgow Outcome Scale (r=
      0.505, P=0.039) and positively correlated with modified Rankin Scale (r=0.557,
      P=0.020) respectively conducted one month after SAH. Altogether, this is the
      first study showing CSF sTREM-1 dynamics in SAH patients, and exploring the
      correlations of early CSF sTREM-1 levels to patients' severity and prognosis,
      which suggests that TREM-1 may play an important role in the inflammatory cascade
      after SAH and act as a monitoring biomarker facilitated to assess the severity
      and prognosis of SAH patients.

PMID- 27697435
TI  - Distinct inflammatory responses differentiate cerebral infarct from transient
      ischaemic attack.
AB  - We previously reported on a 26-year-old patient who presented early during a
      large and eventually fatal cerebral infarct. Microarray analysis of blood samples
      from this patient demonstrated initially up-regulated and subsequently down
      regulated Granzyme B (GzmB) expression, along with progressive up-regulation of
      genes for S100 calcium binding protein A12 (S100A12) and matrix metalloproteinase
      9 (MMP-9). To confirm these findings, we investigated these parameters in
      patients with suspected stroke presenting within 6h of symptom onset to a single
      centre. Blood samples were taken at enrolment, then 1h, 3h and 24h post-enrolment
      for the examination of cellular, protein and genetic changes. Patients with
      subsequently confirmed ischaemic (n=18) or haemorrhagic stroke (n=11) showed
      increased intracellular concentrations of GzmB in all cell populations
      investigated (CD8+, CD8- and Natural Killer [NK] cells). Infarct patients,
      however, demonstrated significantly reduced GzmB gene expression and increased
      circulating MMP-9 and S100A12 levels in contrast to transient ischaemic attack
      (TIA) patients or healthy controls. Furthermore, a pronounced neutrophilia was
      noted in the infarct and haemorrhage groups, while TIA patients (n=9) reflected
      healthy controls (n=10). These findings suggest a spectrum of immune response
      during stroke. TIA showed few immunological changes in comparison to infarct and
      haemorrhage, which demonstrated inhibition of GzmB production and a rise in
      neutrophil numbers and neutrophil-associated mediators. This implies a greater
      role of the innate immune system. These markers may provide novel targets for
      inhibition and reduction of secondary injury.

PMID- 27697436
TI  - Evidence supporting idarucizumab for the reversal of dabigatran.
AB  - Idarucizumab is a monoclonal antibody fragment specifically targeted to
      dabigatran. It has demonstrated prompt and durable reversal of the anticoagulant
      effects of dabigatran in animal studies and phase 1 studies of young, elderly,
      and renally impaired volunteers. Although elective invasive procedures and most
      bleeding complications in dabigatran-treated patients can be managed by
      temporarily stopping dabigatran therapy and using supportive measures, there are
      rare clinical situations that require urgent reversal of the anticoagulant effect
      of dabigatran. The effectiveness and safety of 5 g of intravenous idarucizumab is
      being investigated in a prospective, open-label, single-cohort study in patients
      with serious bleeding or in those requiring an urgent procedure. In an interim
      analysis of the first 90 participants, idarucizumab rapidly and completely
      reversed the anticoagulant activity of dabigatran in 88%-98% of participants, and
      there were no safety concerns, with no deaths or serious adverse events being
      attributable to idarucizumab. Supported by these interim results, idarucizumab
      has been approved in the United States and the European Union for use when
      reversal of the anticoagulant effects of dabigatran is needed for emergency
      surgery/urgent procedures or in patients with life-threatening or uncontrolled
      bleeding. Clinical use of idarucizumab should follow the same processes as
      patient enrollment in this study, which is projected to be completed in 2016. The
      outcomes achieved with this specific reversal agent are likely to be of continued
      interest to treating physicians.

PMID- 27697434
TI  - Elevation of oxidative stress indicators in a pilot study of plasma following
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) encompasses a broad range of injury mechanisms and
      severity. A detailed determination of TBI severity can be a complex challenge,
      with current clinical tools sometimes insufficient to tailor a clinical response
      to a spectrum of patient needs. Blood biomarkers of TBI may supplement clinical
      assessments but currently available biomarkers have limited sensitivity and
      specificity. While oxidative stress is known to feature in damage mechanisms
      following TBI, investigation of blood biomarkers of oxidative stress has been
      limited. This exploratory pilot study of a subset of 18 trauma patients with TBI
      of varying severity, quantifies circulating concentrations of the structural
      damage indicators S100b, and myelin basic protein (MBP), and the biomarkers of
      oxidative stress hydroxynonenal (HNE), malondialdehyde (MDA), carboxy-methyl
      lysine (CML), and 8-hydroxy-2'-deoxy-guanosine (8-OHDG). Significant increases in
      circulating S100b, MBP, and HNE were observed in TBI patient samples compared to
      8 uninjured controls, and there was a significant decrease in CML. This small
      exploratory study supports the current literature on S100b and MBP elevation in
      TBI, and reveals potential for the use of peripheral oxidative stress markers to
      assist in determination of TBI severity. Further investigation is required to
      validate results and confirm trends.

PMID- 27697437
TI  - Introduction to direct oral anticoagulants and rationale for specific reversal
      agents.

PMID- 27697438
TI  - Idarucizumab and factor Xa reversal agents: role in hospital guidelines and
      protocols.
AB  - As expected with all antithrombotic agents, there is a risk of bleeding
      complications in patients receiving direct oral anticoagulants (DOACs) because of
      the DOAC itself, acute trauma, invasive procedures, or underlying comorbidities.
      For many bleeding events, a prudent course of action will be to withdraw the
      DOAC, then "wait and support" the patient, with the expectation that the bleeding
      event should resolve with time. Likewise, DOAC therapy may be interrupted ahead
      of a planned procedure, the stopping time being dependent on the agent involved
      and the patient's renal function. However, urgent reversal of anticoagulation is
      required in patients with serious or life-threatening bleeding or in those
      requiring urgent surgery or procedures. Novel specific reversal agents, either
      under development or recently approved, will need to be incorporated into local
      anticoagulation reversal protocols. For dabigatran-treated patients, idarucizumab
      recently has been approved for clinical use in cases of life-threatening or
      uncontrolled bleeding or when patients require emergency surgery or urgent
      procedures, both associated with a high risk of bleeding. As clinical experience
      with individual specific reversal agents grows, their roles in managing major
      bleeding events in DOAC-treated patients will become better defined. Future
      research, as well as ongoing use of idarucizumab, should help establish when it
      is appropriate to re-dose with idarucizumab, coadminister with prothrombin
      complex concentrates, or re-initiate DOAC after idarucizumab use. Ongoing trials
      should help identify the appropriate doses and expected durations of effect for
      andexanet alfa and ciraparantag, which are likely to vary depending on the
      individual oral anticoagulants.

PMID- 27697439
TI  - Bleeding with direct oral anticoagulants vs warfarin: clinical experience.
AB  - The risk of bleeding in the setting of anticoagulant therapy continues to be re
      evaluated following the introduction of a new generation of direct oral
      anticoagulants (DOACs). Interruption of DOAC therapy and supportive care may be
      sufficient for the management of patients who present with mild or moderate
      bleeding, but in those with life-threatening bleeding, a specific reversal agent
      is desirable. We review the phase 3 clinical studies of dabigatran, rivaroxaban,
      apixaban, and edoxaban in patients with nonvalvular atrial fibrillation, in the
      context of bleeding risk and management.

PMID- 27697440
TI  - Re-initiation of dabigatran and direct factor Xa antagonists after a major bleed.
AB  - Direct oral anticoagulants (DOACs) are a relatively recent addition to the oral
      anticoagulant armamentarium, and provide an alternative to the use of vitamin K
      antagonists such as warfarin. Regardless of the type of agent used, bleeding is
      the major complication of anticoagulant therapy. The decision to restart oral
      anticoagulation following a major hemorrhage in a previously anticoagulated
      patient is supported largely by retrospective studies rather than randomized
      clinical trials (mostly with vitamin K antagonists), and remains an issue of
      individualized clinical assessment: the patient's risk of thromboembolism must be
      balanced with the risk of recurrent major bleeding. This review provides guidance
      for clinicians regarding if and when a patient should be re-initiated on DOAC
      therapy following a major hemorrhage, based on the existing evidence.

PMID- 27697441
TI  - Safety of direct oral anticoagulants: insights from postmarketing studies.
AB  - Direct oral anticoagulants (DOACs) have been marketed in the United States since
      2010. While numerous large-scale prospective phase 3 outcomes studies have
      documented the effectiveness of DOACs for the prevention of stroke and systemic
      embolism in patients with nonvalvular atrial fibrillation, the primary safety
      concern with all of these drugs-as it is with the more established oral
      anticoagulant warfarin-is the risk of major bleeding. Postmarketing surveillance
      studies (PMSS) provide the opportunity to evaluate the safety of these recently
      approved drugs across a spectrum of patients that may be broader than those
      included in randomized controlled trials. This review will summarize the safety
      findings of numerous recently performed, large-scale PMSS evaluations, and
      consider the currently available evidence regarding the risks for bleeding in
      patients treated with DOACs, in order to give providers and patients additional
      evidence regarding the safety of DOACs.

PMID- 27697442
TI  - Discontinuation and management of direct-acting anticoagulants for emergency
      procedures.
AB  - Patients taking direct oral anticoagulants (DOACs) who then need an emergency
      invasive procedure require specialized management strategies. Appropriate patient
      evaluation includes assessment of the current anticoagulation state, including
      timing of the last dose. DOACs require particular coagulation assays to measure
      anticoagulation levels accurately, although standard coagulation screening tests
      may provide qualitative guidance. Specialty societies have endorsed general
      recommendations for patient management to promote hemostasis in anticoagulated
      patients requiring surgery or other invasive procedures. These include general
      stopping rules (such as >=24 hours for low-risk procedures and >=48 hours for
      high-risk surgery with normal renal function) for elective procedures. Bridging
      therapy when oral anticoagulant treatment is interrupted has recently been
      questioned, depending on the clinical scenario. Novel agents for the reversal of
      DOAC-induced anticoagulation have recently been developed. Idarucizumab, a
      humanized monoclonal antibody fragment that selectively binds dabigatran, was
      recently approved for clinical use in patients with life-threatening or
      uncontrolled bleeding, and for patients requiring emergency interventions.
      Idarucizumab can streamline the pre- and periprocedural anticoagulation
      management of dabigatran-treated patients, as it provides fast, complete, and
      sustainable reversibility. Andexanet alfa is an inactive, decoy factor Xa (FXa)
      molecule that binds FXa inhibitors, and ciraparantag is a synthetic molecule
      designed to bind fractionated and unfractionated heparins, and each of the
      currently approved DOACs. As clinical development of the additional anti-FXa
      specific anticoagulant reversal agents proceeds, the respective role of each in
      the management of emergency bleeding events and invasive procedures will be
      better defined, and it is hoped they will make important contributions to patient
      care.

PMID- 27697443
TI  - Preclinical and clinical data for factor Xa and "universal" reversal agents.
AB  - Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants,
      are frequently used to prevent stroke and systemic embolism in patients with
      atrial fibrillation and to prevent and treat venous thromboembolism. These drugs
      reduce the risk of clotting at the expense of increasing the risk of bleeding,
      and currently they have no specific reversal agent. However, andexanet alfa, a
      recombinant modified FXa decoy molecule, is in a late-phase clinical trial in
      bleeding patients, and ciraparantag, a small molecule that appears to reverse
      many anticoagulants including the FXa inhibitors, is in development. This review
      summarizes the published data to date on both drugs, which have the potential to
      change the management approach to patients with FXa inhibitoreassociated major
      hemorrhage.

PMID- 27697444
TI  - Probiotic Treatment with a Gut Symbiont Leads to Parasite Susceptibility in Honey
      Bees.
AB  - Gut symbionts are critical for host health and as such might be used as
      probiotics. In a recent study, Schwarz et al. showed that pretreatment of honey
      bees with a dominant gut bacterium causes dysbiosis and increases pathogen
      susceptibility, showing that probiotic applications for animal health can have
      unwanted effects.

PMID- 27697445
TI  - Diagnostic accuracy of probe-based confocal laser endomicroscopy in Lugol
      unstained esophageal superficial lesions of patients with head and neck cancer.
AB  - BACKGROUND AND AIMS: Surveillance programs of patients with head and neck cancer
      (HNC) detect synchronous or metachronous esophageal squamous cell carcinoma
      (ESCC) in up to 15% of patients. Noninvasive, probe-based confocal laser
      endomicroscopy (pCLE) technique may improve the diagnosis allowing acquisition of
      high-resolution in vivo images at the cellular and microvascular levels. The aim
      of this study was to evaluate the accuracy of pCLE for the differential diagnosis
      of nonneoplastic and neoplastic Lugol-unstained esophageal lesions in patients
      with HNC. METHODS: Twenty-seven patients with HNC who exhibited Lugol-unstained
      esophageal lesions at surveillance endoscopy were prospectively included for
      pCLE. Diagnostic pCLE was followed by subsequent biopsies or endoscopic resection
      of suspected lesions. A senior pathologist was blinded to the pCLE results.
      RESULTS: Patients mean age was 59 years (SD = 8.8) and 70.4% were men. All
      patients were smokers, and 22 patients (81.5%) had a history of alcohol
      consumption. The locations of HNC were oral cavity (n = 13), larynx (n = 10), and
      pharynx (n = 4). Thirty-seven lesions in 27 patients were studied. The final
      diagnoses were ESCC in 17 patients and benign lesions in 20 patients.
      Sensitivity, specificity, and accuracy of pCLE for the histologic diagnosis of
      ESCC in patients with HNC were 94.1%, 90.0%, and 91.9%, respectively.
      CONCLUSIONS: First, pCLE is highly accurate for real-time histology of Lugol
      unstained esophageal lesions in patients with HNC. Second, pCLE may alter the
      management of patients under surveillance for ESCC, guiding biopsies and
      endoscopic resection, avoiding further diagnostic workup or therapy of benign
      lesions.

PMID- 27697446
TI  - Coadministration of puerarin (low dose) and zinc attenuates bone loss and
      suppresses bone marrow adiposity in ovariectomized rats.
AB  - AIMS: Puerarin is a phytoestrogen that shows osteogenic effects. Meanwhile, zinc
      stimulates bone formation and inhibits bone resorption. The study aims to
      investigate the effects of coadministration of puerarin (low dose) and zinc on
      bone formation in ovariectomized rats. MATERIALS AND METHODS: Co-administration
      or use alone of puerarin (low dose) and/or zinc were gavaged in OVX rats. The
      estrogen-like effects were detected by the uterus weight, the histologic
      observation and the IGF-1 protein expression. The osteogenic effects were
      determined by bone histomorphometric and mechanical parameters, osteogenic and
      adipogenic blood markers, and so on. KEY FINDINGS: The results showed that oral
      administration of puerarin (low dose) plus zinc didn't significantly increase
      uterus weight. The glandular epithelial of endometrium had no proliferation and
      no protein expression of IGF-1. Moreover, co-administration attenuated bone loss
      and biomechanical decrease more than single use of puerarin or zinc (p<0.05).
      Next, combined administration of puerarin and zinc promoted the serological level
      of osteocalcin, bone marrow stromal cell (BMSC) proliferation, and the expression
      of alkaline phosphatase (ALP), and suppressed the serological level of
      adiponectin and adiposity in bone marrow (BM). SIGNIFICANCE: In conclusion, co
      administrated puerarin (low dose) and zinc can partially reverse OVX-induced bone
      loss and suppress the adiposity of BM in rats, which shed light on the potential
      use of puerarin and zinc in the treatment of osteoporosis.

PMID- 27697448
TI  - Endothelial nitric oxide synthase gene polymorphisms are associated with
      cardiovascular risks in prehypertensives.
AB  - Though endothelial nitric oxide synthase (eNOS) gene polymorphism is documented
      in the causation of hypertension, its role in prehypertension has not been
      investigated. The present study was conducted in 172 subjects divided into
      prehypertensives (n = 57) and normotensives (n = 115). Cardiovascular (CV)
      parameters including baroreflex sensitivity (BRS) by continuous BP variability
      assessment and sympathovagal imbalance (SVI) by heart rate variability analysis
      were recorded. Biochemical parameters for insulin resistance (homeostatic model
      for assessment of insulin resistance), oxidative stress, lipid risk factors,
      renin, and inflammatory parameters were measured. Genotyping for eNOS
      polymorphisms rs1799983 (298G>T) and rs2070744 (-786T>C) was performed by
      polymerase chain reaction-restriction fragment length polymorphism method.
      Multiple regression analysis was done to assess the association between SVI and
      metabolic markers, and multivariate logistic regression was done to determine the
      prediction of prehypertension status by genotype, BRS, and ratio of low-frequency
      to high-frequency in these subjects. The BP variability, heart rate variability,
      and biochemical parameters were significantly altered in prehypertensives. The
      eNOS polymorphisms were found to be associated with prehypertension. BRS, the
      marker of SVI, was significantly associated with BP, homeostatic model for
      assessment of insulin resistance, and tumor necrosis factor alpha in 298GG
      genotype of prehypertensive population. The eNOS gene polymorphisms appear to be
      associated with prehypertension. 298G>T and -786T>C contribute to SVI in young
      prehypertensives attributed by insulin resistance and inflammation. The CV risks
      were associated with prehypertension status in prehypertensives expressing both
      298GG and -786TT genotypes. Association of CV risks with SVI appears to be
      stronger in prehypertensives expressing GG genotype.

PMID- 27697447
TI  - The association between Self-Reported Medication Adherence scores and systolic
      blood pressure control: a SPRINT baseline data study.
AB  - We examined baseline data from the Systolic Blood Pressure Intervention Trial
      (SPRINT) to investigate whether medication adherence, measured by the 8-item
      Morisky Medication Adherence Scale (MMAS-8), was associated with systolic blood
      pressure (SBP) and whether MMAS-8 score and number of antihypertensive
      medications interacted in influencing SBP. A total of 8435 SPRINT participants
      were included: 21.2% had low adherence (MMAS-8: <6); 40.0% had medium adherence
      (6 to <8); and 38.8% had high adherence (8). SBP was <140 mm Hg in 54.6%; 140-160
      mm Hg in 36.6%; and >160 mm Hg in 8.8%. In multivariable regression, medium vs.
      low adherence weakly associated with lower SBP (odds ratio: 1.17; confidence
      interval: 1.04, 1.31). SPRINT eligibility criteria should be considered when
      interpreting results. Efforts to understand and enhance adherence are crucial to
      improve population health, and using self-report instruments might be considered
      for predicting treatment adherence and response in future efficacy trials and for
      identifying patients for adherence support in clinical practice.

PMID- 27697449
TI  - A Longitudinal Investigation of Anxiety and Depressive Symptomatology and
      Exercise Behaviour Among Adults With Type 2 Diabetes Mellitus.
AB  - OBJECTIVES: Evidence suggests that symptoms of depression and anxiety predict
      lower exercise behaviour and, inversely, that less exercise predicts higher
      symptomatology. The present longitudinal study examined this reciprocal
      association in adults with type 2 diabetes mellitus. We predicted that symptoms
      of anxiety or depression would intensify over time as a consequence of lower
      exercise frequency and, similarly, that exercise frequency would decrease as a
      consequence of greater symptoms of anxiety or depression. METHODS: We studied
      1691 adults with type 2 diabetes who provided baseline measures in 2011 and 2
      subsequent annual assessments (Follow-up 1 and Follow-up 2). Symptoms of
      depression and anxiety were measured using the Patient Health Questionnaire-9 and
      the Generalized Anxiety Disorder-7, respectively. A single item assessed exercise
      frequency in the past month (in days). RESULTS: Separate 3-wave cross-lagged path
      models for symptoms of anxiety and depression tested the reciprocal associations.
      Contrary to our hypotheses, the reciprocal associations were not supported and,
      by extension, the predicted secondary associations were not tested. In sum, only
      depressive symptoms negatively predicted subsequent exercise frequency (Follow-up
      1 and Follow-up 2). CONCLUSIONS: Symptoms of depression were prospectively
      associated with lower exercise frequency, which is consistent with evidence from
      population-based studies that identify depressive symptoms as a barrier to
      exercise participation.

PMID- 27697450
TI  - Screening for REM sleep behavior disorder in the general population.

PMID- 27697451
TI  - Does being overweight affect seminal variables in fertile men?
AB  - The effect of being overweight on seminal variables was assesed in 165 fertile
      men. Participants were divided into three groups: fertile men with normal body
      mass index (BMI) (18.5-24.9 kg/m2), fertile overweight men (BMI 25-29.9 kg/m2)
      and fertile obese men (BMI >30 kg/m2). Medical history was taken, a clinical
      examination conducted. Semen analysis was undertaken and BMI measured. Seminal
      reactive oxygen species (ROS) was estimated by chemiluminescent assay, sperm
      vitality by the hypo-osmotic swelling test and sperm DNA fragmentation by
      propidium iodide staining with flowcytometry. Fertile obese men had significantly
      lower sperm concentration, progressive sperm motility and sperm normal
      morphology, with significantly higher seminal ROS and sperm DNA fragmentation
      compared with fertile normal-weight men and overweight men (all P < 0.05). BMI
      was negatively correlated with sperm concentration (r = -0.091; P = 0.014),
      progressive sperm motility (r = -0.697; P = 0.001), normal sperm morphology (r = 
      0.510; P = 0.001), sperm vitality (r = -0.586; P = 0.001), but positively
      correlated with sperm DNA fragmentation percentage (r = 0.799; P = 0.001) and
      seminal ROS (r = 0.673; P = 0.001). Increased BMI was found to affect semen
      parameters negatively even in fertile men.

PMID- 27697452
TI  - Identification of a novel aviadenovirus, designated pigeon adenovirus 2 in
      domestic pigeons (Columba livia).
AB  - The young pigeon disease syndrome (YPDS) affects mainly young pigeons of less
      than one year of age and leads to crop stasis, vomitus, diarrhea, anorexia and
      occasionally death. This disease is internationally a major health problem
      because of its seasonal appearance during competitions such as homing pigeon
      races or exhibitions of ornamental birds. While the etiology of YPDS is still
      unclear, adenoviruses are frequently discussed as potential causative agents.
      Electron microscopy of feces from a YPDS outbreak revealed massive shedding of
      adenovirus-like particles. Whole genome sequencing of this sample identified a
      novel adenovirus tentatively named pigeon adenovirus 2 (PiAdV-2). Phylogenetic
      and comparative genome analysis suggest PiAdV-2 to belong to a new species within
      the genus Aviadenovirus, for which we propose the name Pigeon aviadenovirus B.
      The PiAdV-2 genome shares 54.9% nucleotide sequence identity with pigeon
      adenovirus 1 (PiAdV-1). In a screening of further YPDS-affected flocks two
      variants of PiAdV-2 (variant A and B) were detected which shared 97.6% nucleotide
      identity of partial polymerase sequences, but only 79.7% nucleotide identity of
      partial hexon sequences. The distribution of both PiAdV-2 variants was further
      investigated in fecal samples collected between 2008 and 2015 from healthy or
      YPDS-affected racing pigeons of different lofts. Independent of their health
      status, approximately 20% of young and 13% of adult pigeon flocks harbored PiAdV
      2 variants. Birds were free of PiAdV-1 or other aviadenoviruses as determined by
      PCRs targeting the aviadenovirus polymerase or the PiAdV-1 fiber gene,
      respectively. In conclusion, there is no indication of a correlation between YPDS
      outbreaks and the presence of PiAdV-2 or other aviadenoviruses, arguing against
      an causative role in this disease complex.

PMID- 27697453
TI  - The functional analysis of distinct tospovirus movement proteins (NSM) reveals
      different capabilities in tubule formation, cell-to-cell and systemic virus
      movement among the tospovirus species.
AB  - The lack of infectious tospovirus clones to address reverse genetic experiments
      has compromised the functional analysis of viral proteins. In the present study
      we have performed a functional analysis of the movement proteins (NSM) of four
      tospovirus species Bean necrotic mosaic virus (BeNMV), Chrysanthemum stem
      necrosis virus (CSNV), Tomato chlorotic spot virus (TCSV) and Tomato spotted wilt
      virus (TSWV), which differ biologically and molecularly, by using the Alfalfa
      mosaic virus (AMV) model system. All NSM proteins were competent to: i) support
      the cell-to-cell and systemic transport of AMV, ii) generate tubular structures
      on infected protoplast and iii) transport only virus particles. However, the NSM
      of BeNMV (one of the most phylogenetically distant species) was very inefficient
      to support the systemic transport. Deletion assays revealed that the C-terminal
      region of the BeNMV NSM, but not that of the CSNV, TCSV and TSWV NSM proteins,
      was dispensable for cell-to-cell transport, and that all the non-functional C
      terminal NSM mutants were unable to generate tubular structures. Bimolecular
      fluorescence complementation analysis revealed that the C-terminus of the BeNMV
      NSM was not required for the interaction with the cognate nucleocapsid protein,
      showing a different protein organization when compared with other movement
      proteins of the '30K family'. Overall, our results revealed clearly differences
      in functional aspects among movement proteins from divergent tospovirus species
      that have a distinct biological behavior.

PMID- 27697454
TI  - Nerve stress during reverse total shoulder arthroplasty: a cadaveric study.
AB  - BACKGROUND: Neurologic lesions are relatively common after total shoulder
      arthroplasty. These injuries are mostly due to traction. We aimed to identify the
      arm manipulations and steps during reverse total shoulder arthroplasty (RTSA)
      that affect nerve stress. METHODS: Stress was measured in 10 shoulders of 5
      cadavers by use of a tensiometer on each nerve from the brachial plexus, with
      shoulders in different arm positions and during different surgical steps of RTSA.
      RESULTS: When we studied shoulder position without prostheses, relative to the
      neutral position, internal rotation increased stress on the radial and axillary
      nerves and external rotation increased stress on the musculocutaneous, median,
      and ulnar nerves. Extension was correlated with increase in stress on all nerves.
      Abduction was correlated with increase in stress for the radial nerve. We
      identified 2 high-risk steps during RTSA: humeral exposition, particularly when
      the shoulder was in a position of more extension, and glenoid exposition. The
      thickness of polyethylene humeral cups used was associated with increased nerve
      stress in all but the ulnar nerve. CONCLUSION: During humeral preparation, the
      surgeon must be careful to limit shoulder extension. Care must be taken during
      exposure of the glenoid. Extreme rotation and oversized implants should be
      avoided to minimize stretch-induced neuropathies.

PMID- 27697455
TI  - Pectoralis major tendon tears: functional outcomes and return to sport in a
      consecutive series of 40 athletes.
AB  - BACKGROUND: There are limited data on the outcomes of surgically repaired
      pectoralis major tendon (PMT) tears. The purpose of this study was to report the
      functional outcomes, return to sport, and second surgery rates in a consecutive
      series of PMT tears. METHODS: Forty patients with acutely repaired PMT tears were
      retrospectively identified. Follow-up was conducted with functional outcome
      scores and adduction strength testing at final follow-up. Return to sport and
      incidence of subsequent surgery were also recorded. RESULTS: The average age of
      the patients was 34.4 years (range, 23-59 years). Average follow-up was 2.5 years
      (range, 2-7.0 years). Twenty-three injuries (58%) occurred in the nondominant
      extremity. Bench press (n = 26) and contact sport participation (n = 14) were the
      most common mechanisms. Postoperative Single Assessment Numeric Evaluation scores
      averaged 93.6 (range, 62-100), with patient satisfaction of 9.6 of 10 (range, 6
      10). All athletes returned to preinjury level of function approximately 5.5
      months postoperatively (range, 4.5-6.5 months); 23.1% and 2.6% described mild or
      moderate difficulties with sport participation. Isokinetic strength evaluation
      revealed an average decrease of 9.9% (range, -18% to 41%). Application of the Bak
      criteria revealed 37% excellent, 26% good, and 37% fair outcomes, with most in
      the fair group reporting cosmetic concerns. Removing cosmesis, 46% scored
      excellent, 37% good, and only 17% fair. Three athletes required a second surgical
      procedure (7.5%). CONCLUSIONS: Surgical repair of PMT tears resulted in high
      patient satisfaction, with excellent restoration of function and adduction
      strength, early return to sport, and few reoperations, albeit with the potential
      for mild cosmetic concerns.

PMID- 27697456
TI  - Prenatal infection leads to ASD-like behavior and altered synaptic pruning in the
      mouse offspring.
AB  - Environmental challenges to the maternal immune system during pregnancy have been
      associated with an increase in the frequency of neurodevelopmental disorders such
      as Autism Spectrum Disorders (ASD) appearing in the offspring. Microglia, the
      brain's resident immune-cells, are now known to be critically involved in normal
      brain development, shaping connections between neurons by pruning superfluous
      synaptic spines. Our aim was to investigate whether maternal infection during
      critical stages of gestation compromises the role of microglia in sculpting
      neuronal circuits. Using a mouse model of maternal immune activation (MIA)
      induced by bacterial Lipopolysaccharide (LPS), we assayed the offspring's
      behavior during postnatal development. Additionally, we quantified spines within
      the offspring's brain and assessed alterations in some molecular signals involved
      in pruning. LPS-induced MIA led to behavioral changes relevant to ASD in the
      offspring in the absence of gross neurological problems. Prenatal LPS resulted in
      a significant increase in the number of spines in the granule cells of the
      dentate gyrus, as well as a reduction in hippocampal expression of the
      fractalkine microglial receptor (CX3CR1), involved in mediating the pruning
      process in the offspring. Interestingly, these changes were only noted in the
      male progeny of the LPS challenged dams. These results provide an early indicator
      that microglial function is altered in the brain of offspring from immune
      challenged mothers and that the effects in the brain appear to be specific along
      sex lines.

PMID- 27697457
TI  - Aryl hydrocarbon receptor-ligand axis mediates pulmonary fibroblast migration and
      differentiation through increased arachidonic acid metabolism.
AB  - Pulmonary fibroblast migration and differentiation are critical events in
      fibrogenesis; meanwhile, fibrosis characterizes the pathology of many respiratory
      diseases. The role of aryl hydrocarbon receptor (AhR), a unique cellular chemical
      sensor, has been suggested in tissue fibrosis, but the mechanisms through which
      the AhR-ligand axis influences the fibrotic process remain undefined. In this
      study, the potential impact of the AhR-ligand axis on pulmonary fibroblast
      migration and differentiation was analyzed using human primary lung fibroblasts
      HFL-1 and CCL-202 cells. Boyden chamber-based cell migration assay showed that
      activated AhR in HFL-1cells significantly enhanced cell migration in response to
      2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), and a known AhR antagonist,
      CH223191, inhibited its migratory activity. Furthermore, the calcium mobilization
      and subsequent upregulated expression of arachidonic acid metabolizing enzymes,
      including cyclooxygenase2 (COX-2) and 5-lipoxygenase (5-LOX), were observed in
      TCDD-treated HFL-1 cells, concomitant with elevated levels of prostaglandin E2
      (PGE2) and leukotriene B4 (LTB4) secretion. Also, significantly increased
      expression of alpha-smooth muscle actin alpha-SMA), a fibroblast differentiation
      marker, was also noted in TCDD-treated HFL-1 cells (p<0.05), resulting in a
      dynamic change in cytoskeleton protein levels and an increase in the nuclear
      translocation of the myocardin-related transcription factor. Moreover, the
      enhanced levels of alpha-SMA expression and fibroblast migration induced by TCDD,
      PGE2 and LTB4 were abrogated by selective inhibitors for COX-2 and 5-LOX.
      Knockdown of AhR by siRNA completely diminished intracellular calcium uptake and
      reduced alpha-SMA protein verified by promoter-reporter assays and chromatin
      immunoprecipitation. Taken together, our results suggested the importance of the
      AhR-ligand axis in fibroblast migration and differentiation through its capacity
      in enhancing arachidonic acid metabolism.

PMID- 27697458
TI  - Real-time EEG artifact correction during fMRI using ICA.
AB  - BACKGROUND: Simultaneous acquisition of EEG and fMRI data results in EEG signal
      contamination by imaging (MR) and ballistocardiogram (BCG) artifacts. Artifact
      correction of EEG data for real-time applications, such as neurofeedback studies,
      is the subject of ongoing research. To date, average artifact subtraction (AAS)
      is the most widespread real-time method used to partially remove BCG and imaging
      artifacts without requiring extra hardware equipment; no alternative software
      only real time methods for removing EEG artifacts are available. NEW METHODS: We
      introduce a novel, improved approach for real-time EEG artifact correction during
      fMRI (rtICA). The rtICA is based on real time independent component analysis
      (ICA) and it is employed following the AAS method. The rtICA was implemented and
      validated during EEG and fMRI experiments on healthy subjects. RESULTS: Our
      results demonstrate that the rtICA employed after the rtAAS can obtain 98.4%
      success in detection of eye blinks, 4.4 times larger INPS reductions compared to
      RecView-corrected data, and effectively reduce motion artifacts, as well as
      imaging and muscle artifacts, in real time on six healthy subjects. COMPARISON
      WITH EXISTING METHODS: We compared our real-time artifact reduction results with
      the rtAAS and various offline methods using multiple evaluation metrics,
      including power analysis. Importantly, the rtICA does not affect brain neuronal
      signals as reflected in EEG bands of interest, including the alpha band.
      CONCLUSIONS: A novel real-time ICA method was proposed for improving the EEG
      quality signal recorded during fMRI acquisition. The results show substantial
      reduction of different types of artifacts using real-time ICA method.

PMID- 27697459
TI  - Hematospermia as a Rare Form of Presentation of Zinner Syndrome.
AB  - A 17-year-old adolescent boy was referred to the urology department of our
      institution for hematospermia after initiation of sexual relationship. A magnetic
      resonance imaging scan showed giant dilation of a multicystic left seminal
      vesicle with left renal agenesis. These findings are typical of the Zinner
      syndrome. In 70%-80% of the cases when renal agenesis is found, there is an
      ipsilateral cystic dilation of the seminal vesicle that in some cases may be
      associated with testicular ectopia or absence of the bladder trigone. The
      ejaculatory ducts, which are formed from the mesonephric system, are abnormally
      developed in these cases.

PMID- 27697460
TI  - Urinary Neurotrophin Levels Increase in Women With Stress Urinary Incontinence
      After a Midurethral Sling Procedure.
AB  - OBJECTIVE: To investigate the association between urinary neurotrophin levels,
      maximum flow rate (Qmax) variation, and the appearance of urgency in women with
      stress urinary incontinence (SUI) after a midurethral sling (MUS) procedure.
      MATERIALS AND METHODS: Thirty-one women with SUI were treated with a MUS. One
      year later, the outcome of surgery and the onset of urgency were assessed. At
      baseline and 1-year follow-up, urine was collected to measure nerve growth factor
      (NGF) and brain-derived neurotrophic factor (BDNF) concentration, and Qmax
      variation was calculated. Urine samples from healthy women (n = 20) without lower
      urinary tract symptoms and overactive bladder (OAB) wet patients (n = 32) were
      used as controls. Urinary neurotrophin levels were measured by enzyme-linked
      immunosorbent assay and normalized to creatinine concentration. RESULTS: At
      baseline, urinary levels of NGF and BDNF were similar between SUI and healthy
      women (NGF: 2.10 +/- 0.68 vs 1.99 +/- 1.05; BDNF: 1.99 +/- 0.71 vs 1.81 +/-
      0.90), and significantly inferior to OAB wet patients (NGF: 2.10 +/- 0.68 vs 2.50
      +/- 0.54, P < .05; BDNF: 1.99 +/- 0.71 vs 2.71 +/- 0.45, P < .05). After surgery,
      there was a significant increase of both neurotrophins (vs baseline, P < .05) to
      the values of OAB wet patients. Moreover, there was a significantly higher
      percentage increase of NGF in women with de novo urgency than in those without
      lower urinary tract symptoms (P = .019). A trend for a higher mean Qmax reduction
      in women with de novo urgency was also found (P = .085). CONCLUSION: These
      findings suggest that increased bladder outlet resistance after a MUS may play a
      key role in the rise of urinary neurotrophins, promoting sensitization of bladder
      primary afferents and causing de novo urgency in susceptible patients.

PMID- 27697461
TI  - Diffusion susceptibility demonstrates relative inhibition potential of sorbent
      immobilized heavy metals against sulfur oxidizing acidophiles.
AB  - A new generation of laminates and cementitious materials incorporate
      antimicrobial metals into domestic infrastructure. Conventional culturing
      approaches are unsuitable for assessing the inhibitory properties of these
      materials. Modifications to the radial Kirby-Bauer antibiotic assay, which
      incorporate metal impregnated activated carbon in linear formats, reveal relative
      metal sensitivities of destructive acidophiles.

PMID- 27697462
TI  - Biological chemistry of hydrogen sulfide and persulfides.
AB  - Hydrogen sulfide (H2S) has been traditionally considered to be a toxic molecule
      for mammals. However, it can be formed endogenously and exert physiological
      effects with potential health benefits. H2S can partition two-fold in biological
      membranes and traverse them rapidly, diffusing between compartments. H2S
      reactivity has similarities to that of thiols, although it is less nucleophilic
      than thiols and it can form different products. H2S can react with oxidants
      derived from the partial reduction of oxygen, but direct scavenging is unlikely
      to explain H2S protective actions. Important effects are exerted on mitochondria
      including the stimulation or the inhibition of the electron transport chain.
      Possible mechanisms for unleashing biological consequences are the reactions with
      metal centers and with thiol oxidation products. The reactions of H2S with
      disulfides (RSSR) and sulfenic acids (RSOH) lead to the formation of persulfides
      (RSSH). Persulfides have enhanced nucleophilicity with respect to the
      corresponding thiol, consistent with the alpha effect. Besides, the inner and
      outer sulfurs can both act as electrophiles. In this review, we describe the
      reactions of H2S with oxidized thiol products and the properties of the
      persulfides formed in the context of the chemical biology of H2S.

PMID- 27697463
TI  - Effects of Depilation Methods on Imiquimod-Induced Skin Inflammation in Mice.

PMID- 27697464
TI  - Selective Substrates and Inhibitors for Kallikrein-Related Peptidase 7 (KLK7)
      Shed Light on KLK Proteolytic Activity in the Stratum Corneum.
AB  - Proteases have pivotal roles in the skin's outermost layer, the epidermis. In the
      stratum corneum, serine proteases from the kallikrein-related peptidase (KLK)
      family have been implicated in several key homeostatic processes, including
      desquamation. However, the precise contribution of specific KLKs to each process
      remains unclear. To address this, we used a chemical biology approach and
      designed selective substrates and inhibitors for KLK7, the most abundant KLK
      protease in the stratum corneum. The resulting KLK7 inhibitor is the most potent
      inhibitor of this protease reported to date (Ki = 140 pM), and displays at least
      1,000-fold selectivity over several proteases that are related by function (KLK5
      and KLK14) or specificity (chymotrypsin). We then used substrates and inhibitors
      for KLK5, KLK7, and KLK14 to explore the activity of each protease in the stratum
      corneum using casein zymography and an ex vivo desquamation assay. These
      experiments provide the most detailed assessment of each KLK's contribution to
      corneocyte shedding in the plantar stratum corneum, revealing that inhibition of
      KLK7 alone is sufficient to block shedding, whereas KLK5 is also a major
      contributor. Collectively, these findings unveil chemical tools for studying KLK
      activity and demonstrate their potential for characterizing KLK biological
      functions in epidermal homeostasis.

PMID- 27697465
TI  - An "all 5 mm ports" technique for laparoscopic day-case anti-reflux surgery: A
      consecutive case series of 205 patients.
AB  - INTRODUCTION: Laparoscopic anti-reflux surgery is conventionally performed using
      two 10/12 mm ports. While laparoscopic procedures reduce post-operative pain, the
      use of larger ports invariably increases discomfort and affects cosmesis. We
      describe a new all 5 mm ports technique for laparoscopic anti-reflux surgery and
      present a review of our initial experience with this approach. METHODS: All
      patients undergoing laparoscopic fundoplication over a 35 month period from
      February 2013 under the care of a single surgeon were included. A Lind
      laparoscopic fundoplication was performed using an all 5 mm port technique. Data
      was recorded prospectively on patient demographics, operating surgeon, surgical
      time, date of discharge, readmissions, complications, need for re-intervention,
      and reasons for admission. RESULTS: Two hundred and five consecutive patients
      underwent laparoscopic fundoplication over the study period. The all 5 mm port
      technique was used in all cases, with conversion to a 12 mm port only once
      (0.49%). Median operating time was 52 min 185 (90.2%) patients were discharged as
      day cases. Increasing ASA grade and the presence of a hiatus hernia were
      associated with the need for overnight stay with admission required in 33% of
      patients with ASA 3, compared to 4% with ASA 1 (p = 0.001), and 29% of those with
      a hiatus hernia vs. 5% without (p < 0.001). No port-related complications
      occurred, and no patients developed recurrence of reflux symptoms. A single
      patient required mesh repair of a large hiatus hernia. CONCLUSION: The all 5 mm
      ports approach to laparoscopic anti-reflux surgery is a safe, efficient, and cost
      effective technique which facilitates same day discharge and minimises port
      related complications. National commissioning guidelines in the UK should target
      quality improvements in anti-reflux surgery based around day-case management.
      This would improve the service for these patients and culminate in cost savings
      for the NHS.

PMID- 27697466
TI  - Diacylglycerol kinases in cancer.
AB  - Diacylglycerol kinases (DGK) are a family of enzymes that catalyze the
      transformation of diacylglycerol into phosphatidic acid. In T lymphocytes,
      DGKalpha and zeta limit the activation of the PLCgamma/Ras/ERK axis, providing a
      critical checkpoint to inhibit T cell responses. Upregulation of these isoforms
      limits Ras activation, leading to hypo-responsive, anergic states similar to
      those caused by tumors. Recent studies have identified DGKalpha upregulation in
      tumor lymphocyte infiltrates, and cells from DGKalpha and zeta deficient mice
      show enhanced antitumor activity, suggesting that limitation of DAG based signals
      by DGK is used by tumors to evade immune attack. DGKalpha expression is low or
      even absent in other healthy cells like melanocytes, hepatocytes or neurons.
      Expression of this isoform, nevertheless is upregulated in melanoma,
      hepatocarcinoma and glioblastoma where DGKalpha contributes to the acquisition of
      tumor metastatic traits. A model thus emerges where tumor milieu fosters DGKalpha
      expression in tumors as well as in tumor infiltrating lymphocytes with opposite
      consequences. Here we review the mechanisms and targets that facilitate tumor
      "addiction" to DGKalpha, and discuss its relevance in the more advanced forms of
      cancer for tumor immune evasion. A better knowledge of this function offers a new
      perspective in the search of novel approaches to prevent inhibition of immune
      attack in cancer. Part of the failure in clinical progress may be attributed to
      the complexity of the tumor/T lymphocyte interaction. As they develop, tumors use
      a number of mechanisms to drive endogenous, tumor reactive T cells to a general
      state of hyporesponsiveness or anergy. A better knowledge of the molecular
      mechanisms that tumors use to trigger T cell anergic states will greatly help in
      the advance of immunotherapy research.

PMID- 27697467
TI  - Frozen section analysis of the pancreatic margin during pancreaticoduodenectomy
      for cancer: Does extending the resection to obtain a secondary R0 provide a
      survival benefit? Results of a systematic review.
AB  - BACKGROUND: During pancreaticoduodenectomy, frozen section pancreatic margin
      analysis permits to extend the resection in case of a positive margin, to achieve
      R0 margin. We aim to assess if patients having an R0 margin following the
      extension of the pancreatectomy after a positive frozen section (secondary R0)
      have different survival compared to those with R1 resection or primary R0
      resection. METHODS: A systematic search was performed to identify all studies
      published up to March 2016 analyzing the survival of patients undergoing
      pancreaticoduodenectomy according to the results of frozen section pancreatic
      margin examination. Clinical effectiveness was synthetized through a narrative
      review with full tabulation of results. RESULTS: Four studies published between
      2010 and 2014 were retrieved, including 2580 patients. A primary R0 resection was
      obtained in a percentage of patients ranging from 36.2% to 85.5%, whereas
      secondary R0 in 9.4%-57.8% of cases and R1 in 5.1%-9.2%. Median survival ranged
      from 19 to 29 months in R0 patients, from 11.9 to 18 months in secondary R0, and
      from 12 to 23 months in R1 patients. None of the study demonstrated a survival
      benefit of extending the resection to obtain a secondary R0 pancreatic margin.
      CONCLUSIONS: All the studies were concordant, and failed to demonstrate the
      survival benefit of additional pancreatic resection to obtain a secondary R0.
      However, inadequate surgery should not be advocated. This review suggests that re
      resection of the pancreatic margin may have limited impact on patients' survival.

PMID- 27697468
TI  - Muscle fatigue effects can be anticipated to reproduce a movement kinematics
      learned without fatigue.
AB  - Muscle fatigue modifies the gain between motor command magnitude and the
      mechanical muscular response. In other words, post-fatigue, central drives to the
      muscles must increase to maintain a particular submaximum mechanical output. In
      this study, we tested the hypothesis that this modified gain can be predicted by
      the central nervous system (CNS) during discrete ballistic movements. In two
      separate experiments, subjects were required to perform shoulder flexions in
      standing and sitting positions at submaximum target peak accelerations. They were
      assisted with visual feedback informing them on their performance after each
      trial. Shoulder flexions were performed before and after fatiguing protocols of
      the focal muscles. Acceleration signals, focal and postural muscle
      electromyograms (EMGs) were recorded. The results demonstrated that participants
      were able to reach with precision the target acceleration during the first
      movements post-fatigue at the cost of significant increase in focal motor command
      magnitude. Decreased variance of peak accelerations associated with increased
      focal command variability was observed post-fatigue. During the standing
      experiment, postural muscle EMGs revealed that anticipatory postural adjustments
      (APAs) scaled to focal movement acceleration post-fatigue. All these results
      support that fatigue effects are taken into account during movement planning.
      Indeed, given that no feedback could enable participants to adjust acceleration
      during movement, this capacity to anticipate fatigue effects is the exclusive
      result of feedforward processes. To account for this prediction capacity, we
      discuss the role of fatigue-related modifications in sensory inputs from the
      working muscles.

PMID- 27697469
TI  - Re: "Surgery in disorders of sex development (DSD) with a gender issue: If (why),
      when, and how?"

PMID- 27697470
TI  - Milestone assessment of minimally invasive surgery in Pediatric Urology
      fellowship programs.
AB  - INTRODUCTION: Minimally invasive surgery has become an important aspect of
      Pediatric Urology fellowship training. In 2014, the Accreditation Council for
      Graduate Medical Education published the Pediatric Urology Milestone Project as a
      metric of fellow proficiency in multiple facets of training, including
      laparoscopic/robotic procedures. OBJECTIVE: The present study assessed trends in
      minimally invasive surgery training and utilization of the Milestones among
      recent Pediatric Urology fellows. STUDY DESIGN: Using an electronic survey
      instrument, Pediatric Urology fellowship program directors and fellows who
      completed their clinical year in 2015 were surveyed. Participants were queried
      regarding familiarity with the Milestone Project, utilization of the Milestones,
      robotic/laparoscopic case volume and training experience, and perceived
      competency with robotic/laparoscopic surgery at the start and end of the
      fellowship clinical year according to Milestone criteria. Responses were accepted
      between August and November 2015. RESULTS: Surveys were distributed via e-mail to
      35 fellows and 30 program directors. Sixteen fellows (46%) and 14 (47%) program
      directors responded. All fellows reported some robotic experience prior to
      fellowship, and 69% performed >50 robotic/laparoscopic surgeries during
      residency. Fellow robotic/laparoscopic case volume varied: three had 1-10 cases
      (19%), four had 11-20 cases (25%), and nine had >20 cases (56%). Supplementary or
      robotic training modalities included simulation (9), animal models (6), surgical
      videos (7), and courses (2). Comparison of beginning and end of fellowship
      robotic/laparoscopic Milestone assessment (Summary Fig.) revealed scores of <3 in
      (10) 62% of fellow self-assessments and 10 (75%) of program director assessments.
      End of training Milestone scores >4 were seen in 12 (75%) of fellow self
      assessment and eight (57%) of program director assessments. DISCUSSION: An
      improvement in robotic/laparoscopic Milestone scores by both fellow self
      assessment and program director assessment was observed during the course of
      training; however, 43% of program directors rated their fellow below the
      graduation target of a Milestone score of 4. CONCLUSION: The best ways to teach
      minimally invasive surgery in fellowship training must be critically considered.

PMID- 27697472
TI  - Open Payments Database: Anti-Vascular Endothelial Growth Factor Agent Payments to
      Ophthalmologists.
AB  - PURPOSE: To analyze anti-vascular endothelial growth factor (anti-VEGF) agent
      associated industry payments to ophthalmologists using the Centers for Medicare
      and Medicaid Services (CMS) Open Payments and Provider Utilization and Payment
      data. DESIGN: Retrospective database review using 2 national databases. METHODS:
      Payments from 2013 to 2014 were analyzed by anti-VEGF agent, payment category,
      and dollar amount. Ranibizumab and aflibercept usage was correlated by performing
      log-ratio analysis. RESULTS: A total of 3207 ophthalmologists received 13 449
      payments totaling $4 454 325 associated with ranibizumab and aflibercept. As 7%
      of ophthalmologists received 90% of payments, the Gini index was 0.92,
      demonstrating unequal distribution of payments. Consulting fees and speaker fees
      were associated with highest payment amounts to fewest providers. For 2383
      providers (74%), greater than 90% of the anti-VEGF payments were associated
      exclusively with either ranibizumab or aflibercept. A total of 1382
      ophthalmologists were matched in both databases. Providers receiving >90% of
      payments from ranibizumab were more likely to use ranibizumab, and those
      receiving >90% of payments from aflibercept were more likely to use aflibercept
      over bevacizumab as compared to those who received no payments. CONCLUSIONS: The
      distribution of all anti-VEGF payments is unequal. Ophthalmologists who received
      aflibercept or ranibizumab payments were more likely to receive the majority of
      payments from one source or the other, but not both. Those who received anti-VEGF
      payments were more likely to use ranibizumab or aflibercept, as compared to off
      label bevacizumab, than those who did not receive any payment.

PMID- 27697471
TI  - Utility of retrograde ureterocelogram in management of complex ureterocele.
AB  - INTRODUCTION: Symptomatic pediatric ureterocele has diverse manifestations,
      making evidence-based management impractical. Thus, detailed visualization of
      ureterocele anatomy prior to first surgical incision is invaluable. Retrograde
      ureterocelogram (RUC) is a simple, underutilized radiologic technique that can be
      performed during cystoscopy. This study sought to determine whether RUC changes
      surgical management by more accurately depicting the complex ureteral and
      ureterocele anatomy, compared with renal ultrasound (US) and voiding
      cystourethrography (VCUG). METHODS: Patients who underwent surgical management of
      ureterocele from 2003 to 2015 were identified; those who received concomitant
      fluoroscopic RUC were selected for the case series. Data collected included:
      demographics, pre-operative evaluation, surgical interventions, and outcomes. The
      RUC images were individually examined, and the anatomic impression compared with
      previous renal US and VCUG. Novel RUC findings not previously appreciated by the
      pre-operative evaluation were noted. The RUC was performed by cystoscopically
      inserting a needle into the ureterocele and injecting contrast retrograde. If
      indicated, simultaneous PIC (Positioning the Instillation of Contrast)
      cystography was performed. RESULTS: Of the 43 patients that underwent surgery for
      suspected ureterocele, 28 underwent cystoscopy + RUC (10 M: 18 F) at a median age
      of 4.6 months and median follow-up of 37.0 months. All patients had prior US, 25
      had prior VCUG, and 20 had prior radionuclide studies. Ureteroceles were either
      duplex system (n = 21) or single system (n = 7); 17 were ectopic into the bladder
      neck or urethra; seven were intravesical; and four were pseudoureteroceles.
      Fourteen patients underwent concomitant transurethral incision of the ureterocele
      (TUIU); two were deferred for surgery; and 11 received concomitant definitive
      surgery (e.g., nephrectomy). The RUC illuminated novel aspects of the anatomy in
      20 of the 28 patients. No adverse events occurred. Notably, in nine of the 28
      children, significant observations from RUC prompted change to the pre-operative
      surgical plan. DISCUSSION: Retrograde ureterocelogram clearly revealed
      ureterocele ectopy, pseudoureterocele, ureterocele disproportion, and unsuspected
      duplex systems, making it a useful adjunct to standard US and VCUG studies.
      Retrograde ureterocelogram can also be used to fluoroscopically verify
      decompression of the ureterocele post incision, document severity of ureteral
      dilation, and teach residents about the great damage generated by ureterocele
      variations. Limitations of RUC included increasing radiation dose and overall
      cost. The study design was limited by its small size, retrospective approach,
      selection bias, and availability of RUC images. CONCLUSIONS: While not indicated
      in routine ureterocele management, intraoperative RUC further defined ureterocele
      anatomy in nearly all cases and yielded changes to the original surgical plan
      frequently enough to merit greater use in complex patients.

PMID- 27697473
TI  - Changes in Keratometric Values and Corneal High Order Aberrations After Hydrogel
      Inlay Implantation.
AB  - PURPOSE: We sought to analyze surgically induced refractive change (SIRC) and
      change in high-order aberration after Raindrop corneal inlay insertion (ReVision
      Optics, Lake Forest, CA), and assess the extent to which Raindrop corneal inlay
      insertion could correct presbyopia. DESIGN: Interventional case series. METHODS:
      Seventeen patients were included if they had a corneal thickness >=500 MUm and a
      stable manifest spherical equivalent refraction between 0.50 and +1.00 diopters
      (D). The Raindrop corneal inlay was implanted on the stromal bed of a femtosecond
      laser-assisted generated flap of nondominant eyes. Manifest refraction, corneal
      powers, and corneal high-order aberrations were measured preoperatively and at 3
      and 12 months postoperatively. RESULTS: The SIRC by manifest refraction was 0.99
      +/- 0.26 D. The changes derived from simulated keratometry (K), true net power,
      and equivalent K reading (EKR) at 1.0-4.0 mm were greater than the SIRC (all P <
      .01) while the change in EKR at 6.0 mm was less than the SIRC (P < .01). The
      changes in EKR 5.0 mm, automated K, and EKR 4.5 mm did not differ significantly
      from the SIRC (P = .81, .29, and .09, respectively), and the difference was the
      least for EKR 5.0 mm. In analysis of high-order aberrations, only spherical
      aberration showed statistically significant difference between preoperative and
      postoperative on both anterior cornea and total cornea (all P < .01). CONCLUSION:
      Raindrop corneal inlay corrects presbyopia via increasing negative spherical
      aberration. The equivalent K reading at 5.0 mm accurately reflected the SIRC, and
      would be applicable for intraocular power prediction before cataract surgery.

PMID- 27697474
TI  - Formation of an Intraretinal Fluid Barrier in Cavitary Optic Disc Maculopathy.
AB  - PURPOSE: Cavitary optic disc maculopathy develops when fluctuating pressure
      gradients along anomalous communications in the optic nerve head induce migration
      of fluid into the adjacent retinal tissue. We sought to determine whether
      carefully titrated laser photocoagulation combined with vitrectomy and gas
      tamponade can safely create an effective intraretinal barrier to fluid egress
      from the optic disc cavitation. DESIGN: Retrospective interventional case series.
      METHODS: We retrospectively evaluated medical records and imaging studies of 22
      consecutive patients with cavitary disc maculopathy evaluated by a single surgeon
      between 1991 and 2014. Patients requiring surgery underwent carefully titrated
      juxtapapillary laser photocoagulation followed immediately by vitrectomy and gas
      tamponade. Main outcome measures were change in visual acuity, macular fluid
      resolution, and recurrence of maculopathy. RESULTS: Eleven patients (11 eyes) had
      undergone vitreous surgery and were included in the study. No preoperative
      evidence for vitreous traction on the optic disc or macula was seen in any eye.
      Nine patients underwent a single surgery and 2 patients required additional
      procedures to resolve the macular fluid. Mean length of follow-up after the last
      surgery was 48.2 months (range, 4-143 months). All 11 patients (100%) had
      complete resolution of macular fluid, with an average time to resolution of 8.5
      months (range, 1-18 months). Only 1 of 11 patients (9%) had recurrence of macular
      fluid (14 months postoperatively). The average preoperative visual acuity of
      20/125 (logMAR 0.81, standard deviation [SD] = 0.36) improved by nearly 4 lines
      to an average final visual acuity of 20/57 (logMAR 0.45, SD = 0.37) (P = .0072).
      A possible laser-induced central scotoma was suspected in only 1 patient who had
      undergone extensive prior laser treatments. CONCLUSIONS: An effective
      intraretinal barrier to fluid migration from cavitary optic disc anomalies can be
      safely achieved in most patients with carefully titrated juxtapapillary laser
      photocoagulation combined with vitrectomy and gas tamponade. Once achieved, the
      barrier facilitates resolution of macular fluid and long-term avoidance of
      recurrent maculopathy.

PMID- 27697475
TI  - Understanding the core of RNA interference: The dynamic aspects of Argonaute
      mediated processes.
AB  - At the core of RNA interference, the Argonaute proteins (Ago) load and utilize
      small guide nucleic acids to silence mRNAs or cleave foreign nucleic acids in a
      sequence specific manner. In recent years, based on extensive structural studies
      of Ago and its interaction with the nucleic acids, considerable progress has been
      made to reveal the dynamic aspects of various Ago-mediated processes. Here we
      review these novel insights into the guide-strand loading, duplex unwinding, and
      effects of seed mismatch, with a focus on two representative Agos, the human Ago
      2 (hAgo2) and the bacterial Thermus thermophilus Ago (TtAgo). In particular,
      comprehensive molecular simulation studies revealed that although sharing similar
      overall structures, the two Agos have vastly different conformational landscapes
      and guide-strand loading mechanisms because of the distinct rigidity of their L1
      PAZ hinge. Given the central role of the PAZ motions in regulating the exposure
      of the nucleic acid binding channel, these findings exemplify the importance of
      protein motions in distinguishing the overlapping, yet distinct, mechanisms of
      Ago-mediated processes in different organisms.

PMID- 27697476
TI  - Basic units of protein structure, folding, and function.
AB  - Study of the hierarchy of domain structure with alternative sets of domains and
      analysis of discontinuous domains, consisting of remote segments of the
      polypeptide chain, raised a question about the minimal structural unit of the
      protein domain. The hypothesis on the decisive role of the polypeptide backbone
      in determining the elementary units of globular proteins have led to the
      discovery of closed loops. It is reviewed here how closed loops form the loop-n
      lock structure of proteins, providing the foundation for stability and
      designability of protein folds/domain and underlying their co-translational
      folding. Simplified protein sequences are considered here with the aim to explore
      the basic principles that presumably dominated the folding and stability of
      proteins in the early stages of structural evolution. Elementary functional loops
      (EFLs), closed loops with one or few catalytic residues, are, in turn, units of
      the protein function. They are apparent descendants of the prebiotic ring-like
      peptides, which gave rise to the first functional folds/domains being fused in
      the beginning of the evolution of protein structure. It is also shown how
      evolutionary relations between protein functional superfamilies and folds
      delineated with the help of EFLs can contribute to establishing the rules for
      design of desired enzymatic functions. Generalized descriptors of the elementary
      functions are proposed to be used as basic units in the future computational
      design.

PMID- 27697477
TI  - Lysophosphatidylcholines activate PPARdelta and protect human skeletal muscle
      cells from lipotoxicity.
AB  - Metabolomics studies of human plasma demonstrate a correlation of lower plasma
      lysophosphatidylcholines (LPC) concentrations with insulin resistance, obesity,
      and inflammation. This relationship is not unraveled on a molecular level. Here
      we investigated the effects of the abundant LPC(16:0) and LPC(18:1) on human
      skeletal muscle cells differentiated to myotubes. Transcriptome analysis of human
      myotubes treated with 10MUM LPC for 24h revealed enrichment of up-regulated
      peroxisome proliferator-activated receptor (PPAR) target transcripts, including
      ANGPTL4, PDK4, PLIN2, and CPT1A. The increase in both PDK4 and ANGPTL4 RNA
      expression was abolished in the presence of either PPARdelta antagonist GSK0660
      or GSK3787. The induction of PDK4 by LPCs was blocked with siRNA against PPARD.
      The activation of PPARdelta transcriptional activity by LPC was shown as
      PPARdelta-dependent luciferase reporter gene expression and enhanced DNA binding
      of the PPARdelta/RXR dimer. On a functional level, further results show that the
      LPC-mediated activation of PPARdelta can reduce fatty acid-induced inflammation
      and ER stress in human skeletal muscle cells. The protective effect of LPC was
      prevented in the presence of the PPARdelta antagonist GSK0660. Taking together,
      LPCs can activate PPARdelta, which is consistent with the association of high
      plasma LPC levels and PPARdelta-dependent anti-diabetic and anti-inflammatory
      effects.

PMID- 27697479
TI  - Primary orbital synovial sarcoma: A clinicopathologic review with a differential
      diagnosis and discussion of molecular genetics.
AB  - Synovial sarcoma is a soft-tissue sarcoma of the extremities developing in young
      adults that has rarely been reported in the orbit. Synovial sarcoma is associated
      with a unique translocation, resulting in an SYT-SSX fusion gene. We analyze 7
      published periocular cases, together with the current one, to gain a better
      appreciation of the features of the tumor in this location and to compare the
      findings with those derived from nonophthalmic studies. An inferior orbital mass
      developed in a 31-year-old woman after experiencing periorbital and hemifacial
      pain for more than a decade. Radiographically, the mass was circumscribed and
      displayed coarse internal calcifications. A large but subtotal excision with
      histopathologic examination disclosed a primitive tumor composed of spindled and
      ovoid cells. Immunohistochemistry demonstrated positivity for nuclear transducin
      like enhancer of split 1 and membranous CD99, typical for synovial sarcoma.
      Fluorescence in situ hybridization identified a (X,18) translocation in the tumor
      cells. The patient underwent postoperative adjuvant proton beam radiotherapy with
      a good response that has been maintained during 1 year of follow-up. Orbital soft
      tissue tumors of all types are increasingly identified by their distinctive
      genetic signatures that offer more specificity than standard immunohistochemical
      tests.

PMID- 27697480
TI  - Gene therapy and respiratory neuroplasticity.
AB  - Breathing is a life-sustaining behavior that in mammals is accomplished by
      activation of dedicated muscles responsible for inspiratory and expiratory forces
      acting on the lung and chest wall. Motor control is exerted by specialized pools
      of motoneurons in the medulla and spinal cord innervated by projections from
      multiple centers primarily in the brainstem that act in concert to generate both
      the rhythm and pattern of ventilation. Perturbations that prevent the
      accomplishment of the full range of motor behaviors by respiratory muscles
      commonly result in significant morbidity and increased mortality. Recent
      developments in gene therapy and novel targeting strategies have contributed to
      deeper understanding of the organization of respiratory motor systems. Gene
      therapy has received widespread attention and substantial progress has been made
      in recent years with the advent of improved tools for vector design. Genes can be
      delivered via a variety of plasmids, synthetic or viral vectors and cell
      therapies. In recent years, adeno-associated viruses (AAV) have become one of the
      most commonly used vector systems, primarily because of the extensive
      characterization conducted to date and the versatility in targeting strategies.
      Recent studies highlight the power of using AAV to selectively and effectively
      transduce respiratory motoneurons and muscle fibers with promising therapeutic
      effects. This brief review summarizes current evidence for the use of gene
      therapy in respiratory disorders with a primary focus on interventions that
      address motor control and neuroplasticity, including regeneration, in the
      respiratory system.

PMID- 27697481
TI  - Differential induction of dyskinesia and neuroinflammation by pulsatile versus
      continuous l-DOPA delivery in the 6-OHDA model of Parkinson's disease.
AB  - Neuroinflammation is associated with l-DOPA treatment in Parkinson's disease
      (PD), suggesting a role in l-DOPA-induced dyskinesia (LID), however it is unclear
      whether increased inflammation is specifically related to the dyskinetic outcome
      of l-DOPA treatment. Diversely from oral l-DOPA, continuous intrajejunal l-DOPA
      infusion is associated with very low dyskinetic outcome in PD patients. We
      reproduced these regimens of administration in 6-OHDA-lesioned hemiparkinsonian
      rats, where dyskinetic responses and striatal neuroinflammation induced by
      chronic pulsatile (DOPAp) or continuous (DOPAc) l-DOPA were compared. Moreover,
      we investigated the contribution of a peripheral inflammatory challenge with
      lipopolysaccharide (LPS), to DOPAp-induced dyskinetic and neuroinflammatory
      responses. Rats 6-OHDA-infused in the medial forebrain bundle received two weeks
      treatment with DOPAp, DOPAc via subcutaneous osmotic minipumps, or DOPAp followed
      by DOPAc. l-DOPA plasma levels were measured in all experimental groups. An
      independent group of rats received one peripheral dose of LPS 24h before DOPAp
      treatment. Abnormal involuntary movements (AIMs) were evaluated as a rat model of
      LID. Immunoreactivity (IR) for OX-42, microglial and neuronal TNF-alpha, iNOS and
      GFAP was quantified in denervated and contralateral striatum. In addition, serum
      TNF-alpha was measured. The 6-OHDA denervation induced a mild microgliosis in the
      striatum two weeks after neurotoxin infusion, and increased TNF-alpha IR in
      microglia. Rats receiving the DOPAp treatment developed AIMs and displayed
      increased striatal OX-42, microglial TNF-alpha, iNOS and GFAP. Moreover, TNF
      alpha IR was also increased in a subpopulation of striatal neurons. Conversely,
      DOPAc did not induce AIMs or inflammatory responses in either drug-naive animals
      or rats that were previously dyskinetic when exposed to DOPAp. Serum TNF-alpha
      was not altered by any l-DOPA treatment. LPS pre-treatment increased the degree
      of DOPAp-induced AIMs and striatal IR for OX-42, TNF-alpha, iNOS and GFAP.
      Altogether the present findings indicate that in the 6-OHDA model, chronic l-DOPA
      induces striatal inflammatory responses, which however depend upon the
      administration regimen and the dyskinetic outcome of drug treatment. The
      potentiation of dyskinetic responses by LPS suggests a reciprocal causal link
      between neuroinflammation and LID.

PMID- 27697482
TI  - Occurency of Giardia duodenalis assemblages in river water sources of Black Sea,
      Turkey.
AB  - A total of 420 environmental water samples and 120 drinking water samples from 45
      different sampling sites of the Black Sea in Turkey were collected between 2012
      and 2014. Genomic DNA was isolated from all the investigated water samples and
      comparativelly analyzed by Loop-mediated isothermal amplification (LAMP) of the
      elongation factor 1 Alfa (EF1alpha) gene, and by nested Polymerase Chain Reaction
      (nPCR) of the small subunit (SSU) rRNA and semi-nested PCR (snPCR) of the
      glutamate dehydrogenase gene (GDH). 141 (58.7%), 125 (52.1%) and 120 (50%)
      samples respectivelly were positive by each method. Out of 240 environmental
      samples collected from 25 sites of Samsun Province have been found positive for
      G. duodenalis by LAMP, nPCR and snPCR, respectively. 55 (30.5%), 50 (27.8%) and
      47 (26.1%) of 180 environmental samples collected from 20 other sampling sites of
      Giresun Province were positive for Giardia by LAMP, nPCR and snPCR, respectively.
      Five PCR products from different samples of the Giresun Province and 10 other
      samples from the Samsun Province were found positive for G. duodenalis assemblage
      B. Five PCR products from Giresun Province and 5 samples from Samsun Province
      were found positive for G. duodenalis assemblage A. This is the first report
      about G. duodenalis assemblages A and B from water samples investigations in
      Black Sea of Turkey.

PMID- 27697478
TI  - Sphingolipids in mitochondria.
AB  - Sphingolipids are bioactive lipids found in cell membranes that exert a critical
      role in signal transduction. In recent years, it has become apparent that
      sphingolipids participate in growth, senescence, differentiation and apoptosis.
      The anabolism and catabolism of sphingolipids occur in discrete subcellular
      locations and consist of a strictly regulated and interconnected network, with
      ceramide as the central hub. Altered sphingolipid metabolism is linked to several
      human diseases. Hence, an advanced knowledge of how and where sphingolipids are
      metabolized is of paramount importance in order to understand the role of
      sphingolipids in cellular functions. In this review, we provide an overview of
      sphingolipid metabolism. We focus on the distinct pathways of ceramide synthesis,
      highlighting the mitochondrial ceramide generation, transport of ceramide to
      mitochondria and its role in the regulation of mitochondrial-mediated apoptosis,
      mitophagy and implications to disease. We will discuss unanswered questions and
      exciting future directions. This article is part of a Special Issue entitled:
      Lipids of Mitochondria edited by Guenther Daum.

PMID- 27697483
TI  - First report of Aedes (Stegomyia) albopictus (Diptera: Culicidae) in Oran, West
      of Algeria.
AB  - The increasing globalisation of trades, human movements and environmental changes
      facilitate the introduction and the establishment of the invasive Asian tiger
      mosquito Aedes albopictus outside its native geographical area. Alerted by the
      complaints about mosquito biting which occurred daytime for the inhabitants of
      the seaside town Ain Turk (West of Algeria), an entomological survey was
      conducted in December 2015 to determine the origin of this nuisance. Among the
      collected mosquitoes, specimens of Ae. albopictus (2 males, 3 females and 3
      pupae) were collected. This is the first observation of that invasive mosquito in
      the west of Algeria which confirms its presence and establishment in
      Mediterranean Africa.

PMID- 27697485
TI  - How to reduce adolescent smoking in low-income and middle-income countries.

PMID- 27697484
TI  - Tobacco use and second-hand smoke exposure in young adolescents aged 12-15 years:
      data from 68 low-income and middle-income countries.
AB  - BACKGROUND: Tobacco use is an important risk factor for non-communicable diseases
      worldwide. However, the global extent and prevalence of tobacco use in
      adolescents is poorly described. Using previously collected survey data, we aimed
      to assess tobacco use and second-hand smoke exposure in young adolescents aged 12
      15 years in 68 low-income and middle-income countries. METHODS: We used data from
      the Global School-based Student Health Survey (2006-13) and the China Global
      Tobacco Youth Survey (2013), which are school-based surveys of young adolescents
      aged 12-15 years that assess health behaviours using a standardised, anonymous,
      self-reported questionnaire. We calculated the prevalence of current tobacco use
      and exposure to second-hand smoke in young adolescents from 68 low-income and
      middle-income countries that collected these data in the surveys. We used a
      multilevel model to estimate the association between parental tobacco use, second
      hand smoke, and adolescent tobacco use, adjusting for sex, age, school, school
      class, country's purchasing power parity, smoking initiation age, national
      prevalence of tobacco use among adults, year the WHO FCTC was ratified for each
      country, proxy of socioeconomic status, and survey year. FINDINGS: The mean
      prevalence of current tobacco use was 13.6%, ranging from 2.8% in Tajikistan to
      44.7% in Samoa. In most countries, the prevalence of tobacco use was higher for
      boys than girls, and higher for adolescents aged 14-15 years than for those aged
      12-13 years. The overall prevalence of second-hand smoke exposure was 55.9%,
      ranging from 16.4% in Tajikistan to 85.4% in Indonesia. Parental tobacco use (as
      reported by the young adolescents), especially maternal use, was associated with
      tobacco use in young adolescents (odds ratio 2.06, 95% CI 1.93-2.19, for maternal
      and 1.29, 1.23-1.35 for paternal use). Second-hand smoke exposure was also a risk
      factor for young adolescents' tobacco use (2.56, 2.43-2.69). However, the
      prevalence of tobacco use was not associated with a country's purchasing power
      parity. INTERPRETATION: Tobacco use and second-hand smoke exposure were frequent
      among young adolescents aged 12-15 years in low-income and middle-income
      countries. Parental tobacco use and second-hand smoke exposure were strongly
      associated with young adolescents' tobacco use. The data emphasise the need to
      strengthen tobacco control interventions and programmes in young adolescents from
      low-income and middle-income countries. FUNDING: This work was partly supported
      by the Young Scholars Program of Shandong University (2015WLJH51), the Shandong
      Provincial Natural Science Foundation (ZR2012HQ033), and the National Natural
      Science Foundation (81302496).

PMID- 27697486
TI  - Enhancing speech envelope by integrating hair-cell adaptation into cochlear
      implant processing.
AB  - Cochlear implants (CIs) bypass some of the mechanisms that underlie normal neural
      behavior as occurs in acoustic hearing. One such neural mechanism is short-term
      adaptation, which has been proposed to have a significant role in speech
      perception. Acoustically-evoked neural adaptation has been mainly attributed to
      the depletion of neurotransmitter in the hair-cell to auditory-nerve synapse and
      is therefore not fully present in CI stimulation. This study evaluated a signal
      processing method that integrated a physiological model of hair-cell adaptation
      into CI speech processing. The linear high-pass adaptation process expanded the
      range of rapid variations of the electrical signal generated by the clinical
      processing strategy. Speech perception performance with the adaptation-based
      processing was compared to that of the clinical strategy in seven CI users. While
      there was large variability across subjects, the new processing improved sentence
      recognition and consonant identification scores in quiet in all the tested
      subjects with an average improvement of 8% and 6% respectively. Consonant
      recognition scores in babble noise were improved at the higher signal-to-noise
      ratios tested (10 and 6 dB) only. Information transfer analysis of consonant
      features showed significant improvements for manner and place of articulation
      features, but not for voicing. Enhancement of within-channel envelope cues was
      confirmed by consonant recognition results obtained with single-channel
      strategies that presented the overall amplitude envelope of the signal on a
      single active electrode. Adaptation-inspired envelope enhancement techniques can
      potentially improve perception of important speech features by CI users.

PMID- 27697487
TI  - Preparation and characterization of N-chitosan as a wound healing accelerator.
AB  - Chitosan is insoluble in water due to its rigid crystalline structure, which has
      significantly restricted its application in wound healing. The objective of this
      study was to synthesize a water-soluble chitosan derivative, N-succinyl-chitosan
      (NSC), and evaluate its ability to accelerate the wound healing process. NSC was
      synthesized with succinic anhydride, hydrochloric acid, and alkaline chitosan
      under optimized conditions, and characterized using Fourier transform infrared,
      proton nuclear magnetic resonance, and X-ray diffraction spectroscopy; thermal
      gravimetric analysis; and a solubility test. The cytotoxicity of NSC was
      investigated in L929 cells, and its antibacterial activity was evaluated by the
      inhibition zone method and bacterial growth curves analysis. The results showed
      that the solubility of NSC was substantially improved compared to chitosan, and
      NSC was non-toxic with good antibacterial properties. An animal wound healing
      test indicated that NSC could significantly reduce the healing time compared to
      chitosan. Histopathological examination suggested that the underlying mechanisms
      of these effects were related to NSC's ability to promote the formation of
      granulation tissue and enhance epithelialization. Collectively, these results
      demonstrate the good potential for NSC to be applied as a wound dressing
      material.

PMID- 27697488
TI  - Bioprocess for the production of recombinant HAP phytase of the thermophilic mold
      Sporotrichum thermophile and its structural and biochemical characteristics.
AB  - Thermophilc mold Sporotrichum thermophile secretes an acidstable and thermostable
      phytase, which finds application as a food and feed additive because of its
      adequate thermostability, acid stability, protease insensitivity and broad
      substrate spectrum. Low extracellular phytase production by the mold is a major
      bottleneck for its application on a commercial scale. We have successfully
      overcome this problem by constitutive secretary expression of codon optimized
      rStPhy under glyceraldehyde phosphate dehydrogenase (GAP) promoter in Pichia
      pastoris. A ~41-fold improvement in rStPhy production has been achieved. Circular
      Dichroism (CD) spectra revealed that rStPhy is composed of 26.65% alpha-helices,
      5.26% beta-sheets and 68.09% random coils at pH 5.0 and 60 degrees C, the optima
      for the enzyme activity. The melting temperature (Tm) of the enzyme is ~73
      degrees C. The 3D structure of rStPhy displayed characteristic signature
      sequences (RHGXRXP and HD) of HAP phytase. The catalytically important amino
      acids (Arg74, His75, Arg78, His368 and Asp369) were identified by docking and
      site directed mutagenesis. Fluorescence quenching by N-bromosuccinimide (NBS) and
      CsCl exposed tryptophan residues surrounded by negative charges, which play a key
      role in maintaining structural integrity of rStPhy.

PMID- 27697489
TI  - Fabrication and characterization of bactericidal thiol-chitosan and chitosan
      iodoacetamide nanofibres.
AB  - Two chitosan derivatives, namely, thiol-chitosan (TCs) and chitosan iodoacetamide
      (CsIA) were newly synthesized by reacting Cs with thiglycolic acid (TGA) and
      iodoacetic acid (IA) respectively. After being crosslinked with glutraldehyde
      (GA), the two derivatives were submitted to FT-IR and H1 NMR analysis for
      identification and characterization of their chemical features. As TCs and CsIA
      are water soluble, their electrospun nanofibres mats from aqueous solutions could
      be crosslinked and achieved using polyvinyl alcohol/Chitosan blend (PVA/Cs)
      polymers. Morphological structures of the obtained nanofibres and their webs were
      studied via those of TCs and CsIA free systems. The data also indicate that the
      crosslinked PVA/Cs/CsIA is more thermally stable than the crosslinked PVA/Cs/TCs
      and crosslinked PVA/Cs respectively. It was proved that the electrospun fibers
      containing TCs or CsIA display a superior antibacterial activity against negative
      bacteria E. Coli with a minimum inhibitory concentration (MIC) of 400MUg/ml.
      These effects are rather in confirmation with bacterial kinetics essays which
      were also carried out in current work. Of particular interest is that the
      antimicrobial properties of fibers containing small concentration of either TCs
      or CsIA are much superior than those obtained with neat Cs electrospun nanofibres
      used as reference. By and large the results advocate the fibers webs containing
      TCs or CsIA as excellent candidates for wound dressing applications.

PMID- 27697490
TI  - Chitin hoops obtained from Ommatoiulus sabulosus (Diplopoda, Julidae) used for
      bovine serum albumin adsorption.
AB  - A new hoop shaped three dimensional chitin was obtained successfully from the
      body segment of a diplopod species (Ommatoiulus sabulosus) by following the
      procedure decolorization, demineralization and deproteinization. Purity of the
      hoop shaped three-dimensional chitin was proved by FT-IR analysis and chitinase
      digestive test. The important bands for alpha-chitin such as 1654.2, 1619.7 and
      1552cm-1 were found after FT-IR analysis. And the chitinase digestive test
      revealed the purity of chitin (with digestion rate of 94.7%). SEM analysis showed
      that the chitin surface consisted of highly porous structure with nanofibers.
      Thermal stability of the hoop shaped chitin was recorded quite high (DTGmax=383
      degrees C). The nitrogen, carbon and hydrogen contents of the hoop shaped chitin
      were determined as 6.81%, 46.23% and 6.43% respectively. And also degree of
      acetylation (DA) of the chitin indicated the purity with 95.85%. Chitin hoops-BSA
      interaction was conducted at different pH, protein concentration and contact
      time. This new type of three-dimensional chitin obtained from the diplopod body
      segments can find more effective applications in further studies comparing to the
      conventional dust forms.

PMID- 27697491
TI  - Mass cultivation of UV-B adapted Arthrospira platensis RRGK under open raceway
      pond for the production of Poly-beta-hydroxy butyrate.
AB  - Six different strains of cyanobacteria were isolated from the freshwater lake,
      Arakkonam, India. Staining of cells with Nile Red showed the presence of large
      quantities of PHB granules in the cell cytoplasm of Arthrospira. Molecular
      identification of the strain was carried out using 16S rRNA analysis and their
      systematic position was ascertained as Arthrospira platensis RRGK. Studies were
      carried out on random mutagenesis approach using UV-B radiation for enhancing the
      production of PHB. Further, Response Surface Methodology was used for
      optimization of pH, temperature, and sodium bicarbonate for higher biomass and
      PHB production. Under open raceway pond A. platensis RRGK produced biomass
      concentration of 2.2+/-0.13gL-1 and 131+/-0.36gL-1 of PHB content. It was
      chemically characterized through FTIR, DSC, TGA and XRD analyses. Hence, PHB can
      be produced from cyanobacteria by sequestering harmful CO2. It can also be used
      as a substitute for synthetic polymers in tissue engineering.

PMID- 27697492
TI  - Blends and composites of exopolysaccharides; properties and applications: A
      review.
AB  - Exopolysaccharides are synthesized by bacteria and secreted into the external
      environment and they may be homopolymeric or heteropolymeric in configuration.
      They are believed to protect bacterial cells from heavy metals, desiccation or
      other environmental effect. EPS exhibit antitumor, anti-HIV, emulsion
      stabilization capacity, shear-thinning activity, suspension ability, high
      viscosities, excellent biocompatibility, high biodegradability and
      immunomodulatory properties. They are widely used in herbicides, functional food,
      nutraceuticals, cosmeceuticals, pharmaceuticals, insecticides, immunomodulation
      and anticoagulants. This review shed light on the properties and versatile
      applications of xanthan, curdlan, hyaluronic acid and dextran blends and
      composites with natural and synthetic polymers.

PMID- 27697493
TI  - Applications of and Barriers to Holistic Self-Care in a Low-Income, High-Risk
      Obstetric Population.
AB  - OBJECTIVE: We examined 1) women's perceptions regarding self-care, 2)
      applications of self-care, and 3) barriers to practicing effective self-care.
      METHODS: Four focus groups were conducted in a low-income, pregnant population.
      Focus group recruitment and discussions took place at a large medical center in a
      medically underserved area of central Georgia. Thirty-two adult pregnant women
      attending a high-risk obstetric clinic were included. Data related to holistic
      self-care were identified and grouped into one of three categories: women's
      valuations of self-care, applications of self-care, and barriers to self-care.
      The results were synthesized and compared to results from a study of postpartum
      women in which the same analytic framework for examining self-care practice was
      applied. RESULTS: Although women tended to understand the importance of self
      care, they had difficulty practicing all forms of self-care on a regular basis
      owing to financial constraints, limited family support, health complications due
      to their high-risk obstetric status, external commitments, and childcare and
      household responsibilities. Applications of self-care were typically inexpensive
      and mainly required time rather than money. CONCLUSIONS: Socioeconomic status
      seems to influence the specific applications of and barriers to self-care. Health
      care providers should be aware of existing low-cost resources in the community
      that may assist prospective and new mothers in tending to their own emotional and
      physical needs. Providers should also discuss the importance of self-care with
      women during the perinatal period. Efforts should be made to educate school
      administrators regarding the impact of spontaneous requests for money for school
      activities, supplies, and field trips on the family budget.

PMID- 27697494
TI  - Women Veterans with Depression in Veterans Health Administration Primary Care: An
      Assessment of Needs and Preferences.
AB  - OBJECTIVE: Depression is the most prevalent mental health condition in primary
      care (PC). Yet as the Veterans Health Administration increases resources for
      PC/mental health integration, including integrated care for women, there is
      little detailed information about depression care needs, preferences,
      comorbidity, and access patterns among women veterans with depression followed in
      PC. METHODS: We sampled patients regularly engaged with Veterans Health
      Administration PC. We screened 10,929 (10,580 men, 349 women) with the two-item
      Patient Health Questionnaire. Of the 2,186 patients who screened positive (2,092
      men, 94 women), 2,017 men and 93 women completed the full Patient Health
      Questionnaire-9 depression screening tool. Ultimately, 46 women and 715 men with
      probable major depression were enrolled and completed a baseline telephone
      survey. We conducted descriptive statistics to provide information about the
      depression care experiences of women veterans and to examine potential gender
      differences at baseline and at seven month follow-up across study variables.
      RESULTS: Among those patients who agreed to screening, 20% of women (70 of 348)
      had probable major depression, versus only 12% of men (1,243 of 10,505). Of the
      women, 48% had concurrent probable posttraumatic stress disorder and 65% reported
      general anxiety. Women were more likely to receive adequate depression care than
      men (57% vs. 39%, respectively; p < .05); 46% of women and 39% of men reported
      depression symptom improvement at the 7-month follow-up. Women veterans were less
      likely than men to prefer care from a PC physician (p < .01) at baseline and were
      more likely than men to report mental health specialist care (p < .01) in the 6
      months before baseline. CONCLUSION AND IMPLICATIONS FOR PRACTICE: PC/mental
      health integration planners should consider methods for accommodating women
      veterans unique care needs and preferences for mental health care delivered by
      health care professionals other than physicians.

PMID- 27697495
TI  - Marine pharmacology: therapeutic targeting of matrix metalloproteinases in
      neuroinflammation.
AB  - Alterations in matrix metalloproteinase (MMP) expression and activity are
      recognized as key pathogenetic events in several neurological disorders. This
      evidence makes MMPs possible therapeutic targets. The search for substances that
      can inhibit MMPs is moving progressively toward the screening of natural
      products. In particular, marine bioprospecting could be promising for the
      discovery of marine natural products with anti-MMP activities. Despite recent
      advances in this field, the possibility of using marine MMP inhibitors (MMPIs)
      for the treatment of neuroinflammation is still under-investigated. Here, we
      review the latest findings in this promising research field and the potential
      that marine MMPIs can have in the management and treatment of various
      neurological diseases.

PMID- 27697496
TI  - Abnormal B-cell maturation in the bone marrow of patients with germline mutations
      in PIK3CD.

PMID- 27697498
TI  - Validation of the Global Allergy and Asthma European Network (GA2LEN) chamber for
      trials in allergy: Innovation of a mobile allergen exposure chamber.
AB  - BACKGROUND: Field clinical trials of pollen allergy are affected by the
      impossibility of predicting and determining individual allergen exposure because
      of many factors (eg, pollen season, atmospheric variations, pollutants, and
      lifestyles). Environmental exposure chambers, delivering a fixed amount of
      allergen in a controlled environmental setting, can overcome these limitations.
      Environmental exposure chambers are currently already used in phase 2, 3, and
      even 4 trials. Unfortunately, few chambers exist in the world, and this makes it
      difficult to perform large, multicenter clinical trials. The new Global Allergy
      and Asthma European Network (GA2LEN) mobile exposure chamber is a step forward
      because the mobility of the chamber makes it convenient for patients to
      participate in clinical testing. OBJECTIVE: This study was made to validate the
      reproducibility, sensitivity, and specificity of the results obtained in the new
      GA2LEN chamber. METHODS: Seventy-two adult patients (19-61 years old) with
      allergic rhinitis with or without asthma caused by grass pollen were included in
      different clinical validation tests. Total symptom scores and total nasal symptom
      scores were recorded at time zero (0) and every 10 minutes during exposures,
      along with nasal and respiratory parameters. RESULTS: Exposure tests confirmed
      the reproducibility between subsequent runs and the sensitivity (P < .00001 vs
      patients exposed to placebo) and specificity (very low score in nonallergic
      subjects) in the GA2LEN chamber. No adverse reactions were recorded during the
      tests. CONCLUSIONS: The mobility of the GA2LEN chamber provides a new,
      potentially effective, and safe way of generating reliable data in allergy
      multicenter clinical trials.

PMID- 27697497
TI  - Physical health conditions and quality of life in adults with primary
      immunodeficiency diagnosed during childhood: A French Reference Center for PIDs
      (CEREDIH) study.
AB  - BACKGROUND: Most children with primary immunodeficiencies (PIDs) now reach
      adulthood. However, few studies have evaluated their health status and health
      related quality of life (HRQoL). OBJECTIVE: To investigate long-term morbidity,
      the French Reference Center for PIDs initiated a prospective multicenter cohort:
      the French Childhood Immune Deficiency Long-term Cohort. The data collected were
      used to assess the physical health condition of patients who reached adulthood
      and the effect on their quality of life. METHODS: Patients were asked to complete
      health status questionnaires. A severity score (grade 1 [mild] to grade 4 [life
      threatening]) was assigned to each health condition. The HRQoL of patients was
      compared with age- and sex-matched French normal values by using the 36-item
      Short-Form Survey (SF-36) HRQoL questionnaire. RESULTS: Among 329 participants,
      the mean age at evaluation was 27.6 years, with a 21-year mean follow-up after
      diagnosis; 43% reported at least 1 grade 4 health condition, and 86% reported at
      least 1 grade 3 (severe) or 4 health condition. Twenty-five (7.6%) patients had
      been treated for cancer. Compared with the French normal values, adults with PIDs
      scored significantly lower for all HRQoL domains. HRQoL was strongly associated
      with the burden of health conditions. The association with grade 4 or grade 3-4
      health conditions was highly significant for all physical and mental domains.
      CONCLUSION: Adults with PIDs diagnosed during childhood experienced a heavy
      burden of health conditions, which affected their HRQoL. Our results emphasize
      the need to closely monitor this vulnerable population.

PMID- 27697499
TI  - Combined blockade of the IL-13 and IL-33 pathways leads to a greater inhibition
      of type 2 inflammation over inhibition of either pathway alone.

PMID- 27697501
TI  - Deoxycholic acid derivatives as inhibitors of P-glycoprotein-mediated multidrug
      efflux.
AB  - Deoxycholic acid derivatives were designed as P-glycoprotein (Pgp, ABCB1)
      inhibitors. Thus the synthesis and the biological activity of methyl deoxycholate
      derivatives 5-10 and their ether analogs 15-20 have been reported. The potency of
      these compounds to modulate Pgp-mediated MDR was evaluated through daunorubicin
      accumulation and potentiation of doxorubicin cytotoxicity in K562/R7 multidrug
      resistant cells overexpressing Pgp. In parallel, their intrinsic toxicity was
      appreciated on K562 sensitive cells. Methyl 12alpha-[(2R or 2S) tetrahydro-2H
      pyran-2-yloxy]-3-oxo-5beta-cholan-24-oate 9b has shown a good efficiency as a Pgp
      inhibitor and a low intrinsic toxicity. Therefore, this derivative constitutes a
      new lead compound which can be used as a starting point to improve the design of
      non-toxic Pgp modulators.

PMID- 27697502
TI  - Turning the Retrospectroscope on Heart Failure With Preserved Ejection Fraction.

PMID- 27697503
TI  - The Challenges of Bedside-to-Bench Research in Pediatric Cardiology.

PMID- 27697504
TI  - Development and evaluation of silver sulfadiazine loaded microsponge based gel
      for partial thickness (second degree) burn wounds.
AB  - Silver sulfadiazine has been frequently used as an antibacterial agent for
      topical treatment of partial thickness burn wounds. In this study, we present the
      preparation of silver sulfadiazine microsponges by w/o/w emulsion solvent
      evaporation method. Formulation variables were optimized by using 32 factorial
      design. The optimized microsponges were characterized by FTIR, DSC, PXRD,
      particle size analysis, SEM analysis and mercury intrusion porosimetry studies.
      Viscosity, texture analysis and ex vivo drug deposition study of optimized
      microsponge loaded gel were also evaluated. The safety of the optimized gel was
      assessed by MTT assay using epidermal keratinocyte (HaCaT) and mouse embryonic
      fibroblast (NIH-3T3) cell lines. In vitro antibacterial studies were carried out
      to compare the antibacterial inhibitory efficiency of the optimized gel against
      the commercial product. The efficacy of the optimized gel was evaluated by the
      partial thickness (second degree) burn wound model in mice. Optimized microsponge
      loaded gel enhanced the drug retaining capacity in the skin layers, by 3 fold
      higher to that of a commercial product. The antibacterial inhibitory efficiency
      of optimized gel was similar to the commercial product against the Staphylococcus
      aureus and Pseudomonas aeruginosa. Optimized gel showed reduced frequency of
      application, no skin irritation, low cytotoxicity on dermal cell lines and
      enhanced wound contraction.

PMID- 27697505
TI  - Computed tomography assessment for transcatheter aortic valve in valve
      implantation: The vancouver approach to predict anatomical risk for coronary
      obstruction and other considerations.
AB  - Valve-in-valve implantation of a transcatheter heart valve into a failed
      bioprosthetic heart valve has emerged as a treatment alternative to repeat
      conventional surgery. This requires careful pre-procedural assessment using non
      invasive imaging to identify patients at risk for procedure related adverse
      events, such as ostial coronary occlusion. Herein we report how to
      comprehensively assess aortic root anatomy using computed tomography prior to
      transcatheter valve implantation for failed bioprosthetic aortic valves.

PMID- 27697506
TI  - Comparison between semiquantitative and quantitative methods for the assessment
      of knee synovitis in osteoarthritis using non-enhanced and gadolinium-enhanced
      MRI.
AB  - OBJECTIVE: To compare different semiquantitative and quantitative methods using
      both non-enhanced and gadolinium-enhanced MRI techniques for the assessment of
      synovitis in knee osteoarthritis (OA). METHODS: Knees with end-stage clinical OA
      in patients undergoing total knee replacement surgery were included in this cross
      sectional study. MRI was performed on all knees. Standard non-enhanced and
      gadolinium-enhanced sequences were acquired. Using non-enhanced MRI, we
      semiquantitatively assessed two features widely used as surrogates for synovitis:
      effusion-synovitis and Hoffa-synovitis. Using gadolinium-enhanced sequences, we
      semiquantitatively assessed synovial thickness. We quantitatively evaluated the
      total synovial volume on the gadolinium-enhanced sequences as well. We assessed
      the correlations of effusion-synovitis and Hoffa-synovitis with synovial
      thickness and volume, applying Spearman correlation analysis. The diagnostic
      performance of both synovitis features on non-enhanced MRI was assessed using
      synovial thickness on gadolinium-enhanced MRI as the reference. RESULTS: A total
      of 104 subjects (one knee per subject) were included. Correlations of effusion
      synovitis with synovial thickness and volume were r = 0.41 and r = 0.43 (P <
      .001) r = 0.32 and r = 0.39 (P < .0001). CONCLUSION: Using synovial thickness
      assessed on gadolinium-enhanced sequences as the reference, effusion-synovitis
      showed superior correlations and sensitivity. Effusion-synovitis should be
      preferred over Hoffa-synovitis as a surrogate marker for synovial thickening, in
      studies of knee OA for which gadolinium-enhanced sequences are not available.

PMID- 27697500
TI  - Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with
      or without hematopoietic cell transplantation.
AB  - BACKGROUND: X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency
      with high morbidity and mortality compared with those seen in healthy subjects.
      Hematopoietic cell transplantation (HCT) has been considered a curative therapy,
      but the procedure has inherent complications and might not be available for all
      patients. OBJECTIVES: We sought to collect data on the clinical presentation,
      treatment, and follow-up of a large sample of patients with XHIGM to (1) compare
      long-term overall survival and general well-being of patients treated with or
      without HCT along with clinical factors associated with mortality and (2)
      summarize clinical practice and risk factors in the subgroup of patients treated
      with HCT. METHODS: Physicians caring for patients with primary immunodeficiency
      diseases were identified through the Jeffrey Modell Foundation, United States
      Immunodeficiency Network, Latin American Society for Immunodeficiency, and
      Primary Immune Deficiency Treatment Consortium. Data were collected with a
      Research Electronic Data Capture Web application. Survival from time of diagnosis
      or transplantation was estimated by using the Kaplan-Meier method compared with
      log-rank tests and modeled by using proportional hazards regression. RESULTS:
      Twenty-eight clinical sites provided data on 189 patients given a diagnosis of
      XHIGM between 1964 and 2013; 176 had valid follow-up and vital status
      information. Sixty-seven (38%) patients received HCT. The average follow-up time
      was 8.5 +/- 7.2 years (range, 0.1-36.2 years). No difference in overall survival
      was observed between patients treated with or without HCT (P = .671). However,
      risk associated with HCT decreased for diagnosis years 1987-1995; the hazard
      ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease
      was a significant predictor of overall survival (hazard ratio, 4.9; 95%
      confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT
      had higher median Karnofsky/Lansky scores than those treated without HCT (P <
      .001). Among patients receiving HCT, 27 (40%) had graft-versus-host disease, and
      most deaths occurred within 1 year of transplantation. CONCLUSION: No difference
      in survival was observed between patients treated with or without HCT across all
      diagnosis years (1964-2013). However, survivors treated with HCT experienced
      somewhat greater well-being, and hazards associated with HCT decreased, reaching
      levels of significantly less risk in the late 1990s. Among patients treated with
      HCT, treatment at an early age is associated with improved survival. Optimism
      remains guarded as additional evidence accumulates.

PMID- 27697507
TI  - Chemokine receptor CXCR2 in dorsal root ganglion contributes to the maintenance
      of inflammatory pain.
AB  - Chemokines and their receptors have been demonstrated to be important
      contributors to the development and maintenance of chronic pain. Recent studies
      showed that chemokine (C-X-C motif) ligand 1 (CXCL1) and its major receptor CXCR2
      are respectively expressed in astrocytes and neurons in the spinal cord and are
      involved in the maintenance of neuropathic pain and inflammatory pain via
      astrocytic-neuronal interaction. Here we investigated how CXCL1 and CXCR2 are
      regulated in the dorsal root ganglion (DRG) after peripheral injection of
      complete Freund's adjuvant (CFA) and its implication in inflammatory pain. CFA
      induced rapid increase of CXCL1 mRNA and protein in the DRG. Double
      immunostaining showed that CXCL1 was colocalized with calcitonin gene-related
      peptide (CGRP), isolectin B4 (IB4), and neurofilament 200 (NF200). Furthermore,
      CXCR2 mRNA was increased 3h after CFA injection and maintained for more than 3
      days. CXCR2 protein was also increased and colocalized with CGRP, IB4, and NF200.
      Finally, perisciatic nerve injection of CXCR2 siRNA to specifically knock down
      CXCR2 in the DRG effectively attenuated CFA-induced mechanical allodynia and heat
      hyperalgesia, and the effect maintained for more than 5 days. Taken together, our
      results demonstrated that CXCL1 and CXCR2 may regulate the maintenance of
      inflammatory pain via an autocrine/paracrine way in DRG neurons.

PMID- 27697508
TI  - A Huge Abdominal Mass.

PMID- 27697509
TI  - An Unusual Cause of Persistent Abdominal Pain.

PMID- 27697510
TI  - An Exceptional Cause of Abdominal Pain.

PMID- 27697511
TI  - Liposomal systems as viable drug delivery technology for skin cancer sites with
      an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for
      skin conditions'.
AB  - Skin cancer is among one of the most common human malignancies wide-spread world
      over with mortality statistics rising continuously at an alarming rate. The
      increasing frequency of these malignancies has marked the need for adopting
      effective treatment plan coupled with better and site-specific delivery options
      for the desired therapeutic agent's availability at the affected site. The
      concurrent delivery approaches to cancerous tissues are under constant challenge
      and, as a result, are evolving and gaining advancements in terms of delivery
      modes, therapeutic agents and site-specificity of the therapeutics delivery. The
      lipid-based liposomal drug delivery is an attractive and emerging option, and
      which is meticulously shaping up beyond a threshold level to a promising, and
      viable route for the effective delivery of therapeutic agents and other required
      injuctions to the skin cancer. An update on liposomal delivery of
      chemotherapeutic agents, natural-origin compounds, photosensitizer, and DNA
      repair enzymes as well as other desirable and typical delivery modes employed in
      drug delivery and in the treatment of skin cancers is discussed in details.
      Moreover, liposomal delivery of nucleic acid-based therapeutics, i.e., small
      interfering RNA (siRNA), mRNA therapy, and RGD-linked liposomes are among the
      other promising novel technology under constant development. The current clinical
      applicability, viable clinical plans, future prospects including transport
      feasibility of delivery vesicles and imaging techniques in conjunction with the
      therapeutic agents is also discussed. The ongoing innovations in liposomal drug
      delivery technology for skin cancers hold promise for further development of the
      methodology for better, more effective and site-specific delivery as part of the
      better treatment plan by ensuring faster drug transport, better and full payload
      delivery with enough and required concentration of the dose.

PMID- 27697512
TI  - DHCR7: A vital enzyme switch between cholesterol and vitamin D production.
AB  - The conversion of 7-dehydrocholesterol to cholesterol, the final step of
      cholesterol synthesis in the Kandutsch-Russell pathway, is catalyzed by the
      enzyme 7-dehydrocholesterol reductase (DHCR7). Homozygous or compound
      heterozygous mutations in DHCR7 lead to the developmental disease Smith-Lemli
      Opitz syndrome, which can also result in fetal mortality, highlighting the
      importance of this enzyme in human development and survival. Besides serving as a
      substrate for DHCR7, 7-dehydrocholesterol is also a precursor of vitamin D via
      the action of ultraviolet light on the skin. Thus, DHCR7 exerts complex
      biological effects, involved in both cholesterol and vitamin D production.
      Indeed, we argue that DHCR7 can act as a switch between cholesterol and vitamin D
      synthesis. This review summarizes current knowledge about the critical enzyme
      DHCR7, highlighting recent findings regarding its structure, transcriptional and
      post-transcriptional regulation, and its links to vitamin D synthesis. Greater
      understanding about DHCR7 function, regulation and its place within cellular
      metabolism will provide important insights into its biological roles.

PMID- 27697515
TI  - Death by suicide in US military during the Afghanistan and Iraq wars.

PMID- 27697513
TI  - Synthesis and optimization of ceftriaxone-loaded solid lipid nanocarriers.
AB  - The use of nanocarriers to enhance drug delivery efficacy has been increasing in
      the healthcare field due to their tunable surface properties. In this study,
      ceftriaxone-loaded solid lipid nanoparticles (CL-SLNPs) were synthesized using a
      water-in-oil-in-water (w/o/w) type double emulsification method. The formulation
      was optimized using response surface methodology (RSM) and was characterized
      using transmission electron microscopy (TEM), photon correlation spectroscopy
      (PCS), and UV-vis and Fourier transform infrared (FTIR) spectroscopy. The CL
      SLNPs were of spherical shape, 15-20nm in size, and retained the properties of
      the drug or other constituents/ingredients after loading. The prepared
      nanoformulation offered sustained drug release after 24h, while ceftriaxone
      sodium followed a burst release. Antibacterial activity of the nanoformulation
      was evaluated against different gram-positive and gram-negative bacterial
      strains. The minimum inhibitory concentration of CL-SLNPs against Pseudomonas
      aeruginosa was determined as 31MUg/mL.

PMID- 27697514
TI  - Time-varying associations of suicide with deployments, mental health conditions,
      and stressful life events among current and former US military personnel: a
      retrospective multivariate analysis.
AB  - BACKGROUND: US military suicides have increased substantially over the past
      decade and currently account for almost 20% of all military deaths. We
      investigated the associations of a comprehensive set of time-varying risk factors
      with suicides among current and former military service members. METHODS: We did
      a retrospective multivariate analysis of all US military personnel between 2001
      and 2011 (n=110 035 573 person-quarter-years, representing 3 795 823 service
      members). Outcome was death by suicide, either during service or post-separation.
      We used Cox proportional hazard models at the person-quarter level to examine
      associations of deployment, mental disorders, history of unlawful activity,
      stressful life events, and other demographic and service factors with death by
      suicide. FINDINGS: The strongest predictors of death by suicide were current and
      past diagnoses of self-inflicted injuries, major depression, bipolar disorder,
      substance use disorder, and other mental health conditions (compared with service
      members with no history of diagnoses, the hazard ratio [HR] ranged from 1.4 [95%
      CI 1.14-1.72] to 8.34 [6.71-10.37]). Compared with service members who were never
      deployed, hazard rates of suicide (which represent the probability of death by
      suicide in a specific quarter given that the individual was alive in the previous
      quarter) were lower among the currently deployed (HR 0.50, 95% CI 0.40-0.61) but
      significantly higher in the quarters following first deployment (HR 1.51 [1.17
      1.96] if deployed in the previous three quarters; 1.14 [1.06-1.23] if deployed
      four or more quarters ago). The hazard rate of suicide increased within the first
      year of separation from the military (HR 2.49, 95% CI 2.12-2.91), and remained
      high for those who had separated from the military 6 or more years ago (HR 1.63,
      1.45-1.82). INTERPRETATION: The increased hazard rate of death by suicide for
      military personnel varies by time since exposure to deployment, mental health
      diagnoses, and other stressful life events. Continued monitoring is especially
      needed for these high-risk individuals. Additional information should be gathered
      to address the persistently raised risk of suicide among service members after
      separation. FUNDING: Partly funded by the Naval Research Program.

PMID- 27697516
TI  - Outer membrane protein 100 of Aggregatibacter actinomycetemcomitans act as a
      biopharmaceutical target for photodynamic therapy: An in silico analysis.
AB  - BACKGROUND: Periodontitis is a polymicrobial, chronic, and degenerative disease
      that can lead to destruction of the teeth-supporting tissues and eventually to
      loss of teeth. Aggregatibacter actinomycetemcomitans is predominantly associated
      with periodontal diseases. Outer membrane protein (Omp) 100 is a more important
      virulence factor of A. actinomycetemcomitans due to the effect of adhesion and
      invasion into human gingival epithelial cells. Attachment of A.
      actinomycetemcomitans inhibition is significant in the treatment process.
      METHODS: We evaluated the capacity of Omp100 in A. actinomycetemcomitans as a
      novel target for photodynamic therapy (PDT) using a range of bioinformatic tools.
      In silico analysis was used to predict molecular modeling, the hierarchical
      nature of protein structure and backbone, and sub-cellular localization. RESULTS:
      The results showed that Omp100 is most similar to thiamine-phosphate
      pyrophosphorylase [Haemophilus influenzae PittGG], with a 74% similarity. The
      predicted structure of Omp100 displayed that it is a protein with positive charge
      (10.4) in pH 7 and alpha helix dominates other secondary structures located
      outside the cell. Protein-protein interaction network showed that Omp100
      interacted with extracellular matrix protein adhesion, glycoside hydrolase, Omp
      64, phospholipase D/Transphosphatidylase, Flp pilus assembly protein, and heme
      acquisition system receptor. CONCLUSION: According to the results, anionic
      indocyanine green tends to interact with Omp100 during PDT as a major target.

PMID- 27697517
TI  - Neuroprotective effects of cyanidin against Abeta-induced oxidative and ER stress
      in SK-N-SH cells.
AB  - This study evaluated the mechanisms underlying the protective effect of cyanidin
      against Abeta25-35-induced neuronal cell death in SK-N-SH cells. Abeta25-35
      induced neurotoxicity is characterized by a decrease in cell viability, inducing
      the expression of endoplasmic reticulum (ER) stress proteins; an increase in
      intracellular reactive oxygen species (ROS) production; and an increase in
      intracellular calcium release. Abeta25-35 also induces neuronal toxicity through
      the disturbance of ER calcium levels. Pretreatment with cyanidin significantly
      attenuated the Abeta25-35-induced loss of cell viability, reducing the expression
      of endoplasmic reticulum (ER) stress response proteins with regard to the down
      regulation of the expression levels of 78 kDa glucose regulated protein (Grp78),
      phosphorylated forms of pancreatic ER elF2alpha kinase (PERK), eukaryotic
      initiation factor 2 alpha (eIF2alpha), and inositol-requiring enzyme 1 (IRE1),
      and the expression levels of X-box binding protein 1 (XBP-1), activating
      transcription factor 6 (ATF6), and CCAAT/enhancer binding protein homologous
      transcription factor (C/EBP) homologous protein (CHOP); decreased intracellular
      ROS production; decreased intracellular calcium release; and reduced down
      regulation of the protein expression levels of calpain and cleaved caspase-12.
      This result suggests that cyanidin may be an alternative agent in preventing
      neurodegenerative diseases.

PMID- 27697518
TI  - Metabolic flexibility of mitochondrial respiratory chain disorders predicted by
      computer modelling.
AB  - Mitochondrial respiratory chain dysfunction causes a variety of life-threatening
      diseases affecting about 1 in 4300 adults. These diseases are genetically
      heterogeneous, but have the same outcome; reduced activity of mitochondrial
      respiratory chain complexes causing decreased ATP production and potentially
      toxic accumulation of metabolites. Severity and tissue specificity of these
      effects varies between patients by unknown mechanisms and treatment options are
      limited. So far most research has focused on the complexes themselves, and the
      impact on overall cellular metabolism is largely unclear. To illustrate how
      computer modelling can be used to better understand the potential impact of these
      disorders and inspire new research directions and treatments, we simulated them
      using a computer model of human cardiomyocyte mitochondrial metabolism containing
      over 300 characterised reactions and transport steps with experimental parameters
      taken from the literature. Overall, simulations were consistent with patient
      symptoms, supporting their biological and medical significance. These simulations
      predicted: complex I deficiencies could be compensated using multiple pathways;
      complex II deficiencies had less metabolic flexibility due to impacting both the
      TCA cycle and the respiratory chain; and complex III and IV deficiencies caused
      greatest decreases in ATP production with metabolic consequences that parallel
      hypoxia. Our study demonstrates how results from computer models can be compared
      to a clinical phenotype and used as a tool for hypothesis generation for
      subsequent experimental testing. These simulations can enhance understanding of
      dysfunctional mitochondrial metabolism and suggest new avenues for research into
      treatment of mitochondrial disease and other areas of mitochondrial dysfunction.

PMID- 27697519
TI  - Mechanical perspectives on the anterior-posterior axis polarization of mouse
      implanted embryos.
AB  - In most mammals, embryonic development and growth proceed in the maternal uterus.
      Mouse late blastocyst embryos implant on the uterine epithelium around embryonic
      day (E)4.5, and immediately afterward the whole embryo's shape is dynamically
      changed from a bowl-like shape to an elongated egg-cylinder until E5.5.
      Concurrently, mouse anterior-posterior (A-P) axis polarization occurs by the
      emergence of distal visceral endoderm (DVE) cells at the cellular and molecular
      levels as the proximal-distal (P-D) axis. The embryonic growth and axis
      polarization are considered to be controlled primarily by multiple growth
      factors' signaling. However, the precise cellular mechanisms of DVE formation in
      which this signaling is involved have been unclear. We recently identified that
      local breaching of the basement membrane (BM) between the epiblast and the
      visceral endoderm (VE) at the distal tip allows inner epiblast cells to
      transmigrate into the outer VE layer as the emergence of DVE cells. More
      importantly, the local BM loss in the distal region appears to be triggered by
      mechanical forces exerted from maternal tissues on embryos and embryonic growth
      itself. Our data suggest a fascinating hypothesis concerning mouse A-P axis
      polarization mediated by the whole embryo's shape change through mechanical
      stress between the embryo and the uterine epithelium. Our mechanical model
      provides a unique insight into why the first axis polarity of the implanted mouse
      embryo is established in the P-D direction initially and not in the future A-P
      direction. We also discuss whether the local breaching of the BM mediated by
      mechanical cues is essential to mouse A-P axis polarization in in vitro culture.

PMID- 27697520
TI  - Forces driving cell sorting in the amphibian embryo.
AB  - Adhesion differences are the main driver of cell sorting and related processes
      such as boundary formation or tissue positioning. In the early amphibian embryo,
      graded variations in cadherin density and localized expression of adhesion
      modulating factors are associated with regional differences in adhesive
      properties including overall adhesion strength. The role of these differences in
      embryonic boundary formation has not been studied extensively, but available
      evidence suggests that adhesion strength differentials are not essential. On the
      other hand, the inside-out positioning of the germ layers is correlated with
      adhesion strength, although the biological significance of this effect is
      unclear. By contrast, the positioning of dorsal mesoderm tissues along the
      anterior-posterior body axis is essential for axis elongation, but the underlying
      sorting mechanism is not correlated with adhesion strength, and may rely on
      specific cell adhesion. Formation of the ectoderm-mesoderm boundary is the best
      understood sorting related process in the frog embryo. It relies on contact
      induced cell repulsion at the tissue interface, driven by Eph-ephrin signaling
      and paraxial protocadherin-dependent self/non-self recognition.

PMID- 27697521
TI  - Activation of arginine vasopressin receptor 1a facilitates the induction of long
      term potentiation in the accessory olfactory bulb of male mice.
AB  - Olfaction plays an important role in social recognition in most mammals. Central
      arginine vasopressin (AVP) plays a role in this olfaction-based recognition. The
      high level of expression of AVP receptors in the accessory olfactory bulb (AOB)
      at the first relay of the vomeronasal system highlights the importance of AVP
      signaling at this stage. We therefore analyzed the effects of AVP on the synaptic
      plasticity of glutamatergic transmission from mitral cells to granule cells in
      AOB slices from male mice. To monitor the strength of the glutamatergic
      transmission, we measured the maximal initial slope of the lateral olfactory
      tract-evoked field potential, which represents the granule cell response to
      mitral cell activation. AVP paired with 100-Hz stimulation that only produced
      short-term potentiation enhanced the induction of long-term potentiation (LTP) in
      a dose-dependent manner. AVP-paired LTP was blocked by the selective AVP receptor
      1a (AVPR1a) antagonist, d(CH2)5[Tyr(Me)2]AVP (Manning compound), but not by the
      AVPR1b antagonist SSR149415, and it was mimicked by the selective AVPR1a agonist
      [Phe2, Ile3, Orn8]-vasopressin. We further examined the effect of AVP on the
      reciprocal transmission between mitral and granule cells by stimulating a mitral
      cell and recording the evoked inhibitory postsynaptic currents (IPSCs) from the
      same cell using conventional whole-cell patch-clamp techniques. AVP reduced the
      reciprocal IPSCs triggered by endogenous glutamate release from the excited
      mitral cell. These results suggest that AVP promotes the induction of LTP at the
      mitral-to-granule cell synapse via the activation of AVPR1a through an as-yet-to
      be-determined mechanism in the AOB of male mice.

PMID- 27697522
TI  - Golgi protein 73 facilitates the interaction of hepatitis C virus NS5A with
      apolipoprotein E to promote viral particle secretion.
AB  - Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver
      diseases and hepatocellular carcinoma (HCC). Golgi protein 73 (GP73), a resident
      Golgi membrane protein, is a novel serum biomarker for the diagnosis of liver
      diseases and HCC. Although previous studies have demonstrated that HCV
      upregulates GP73 expression and GP73 promotes HCV secretion through its
      interaction with apolipoprotein E (ApoE), the exact mechanism underlying GP73
      regulates HCV secretion remains unclear. In this study, we demonstrated that GP73
      mediates the interaction of ApoE with HCV NS5A protein to promote HCV secretion.
      We revealed that GP73 is colocalized with HCV replication complex in infected
      Huh7.5.1 cells. Further studies demonstrated that GP73 interacted with both NS5A
      and ApoE proteins. Furthermore, knockdown of GP73 significantly reduced the
      binding of NS5A with ApoE, and the production of virus particles in culture
      supernatant. Taken together, our studies revealed that GP73 promotes HCV
      secretion by directly mediating the interaction of ApoE with HCV replication
      complex through binding with HCV NS5A.

PMID- 27697523
TI  - TGF-beta-induced phosphorylation of Akt and Foxo transcription factors negatively
      regulates induced regulatory T cell differentiation.
AB  - Transforming growth factor-beta (TGF-beta) is a pivotal cytokine in the
      differentiation of regulatory T cells, and Foxo transcription factors positively
      regulate this process. On the other hand, the function of Foxo transcription
      factors is negatively regulated by PI3K/Akt signaling, which is activated by TGF
      beta in many types of cells; yet the role of TGF-beta in Akt activity and its
      downstream substrates in CD4+ T cells, including Foxo transcription factors,
      remains to be determined. Herein, we demonstrate that TGF-beta selectively
      induces Akt phosphorylation at Ser473 but not at Thr308 in a class IA PI3K
      dependent manner in CD4+ T cells, resulting in the phosphorylation and inhibition
      of Foxo transcription factors and negatively regulating the differentiation of
      induced regulatory T cells (iTregs). These observations reveal a novel negative
      regulatory mechanism involving Akt and Foxo transcription factors induced by TGF
      beta in the iTreg differentiation process.

PMID- 27697524
TI  - Mouse Apolipoprotein L9 is a phosphatidylethanolamine-binding protein.
AB  - Mouse Apolipoprotein L9 (ApoL9) is an understudied cytoplasmic, interferon
      inducible protein. The details of its intracellular localization and normal
      cellular functions are unclear. We report here that ApoL9 localizes to small
      puncta diffusely distributed in the cytoplasm, as well as to larger granules of
      varying size and number that are similar to aggresome-like induced structures
      (ALIS) and contain the autophagy receptor Sqstm1/p62, the autophagosome marker
      Lc3, and ubiquitin. Transfection of B16F10 mouse melanoma cells stably expressing
      ApoL9 (B16F10L9) with certain liposome-based transfection reagents causes
      dramatic disturbances in its subcellular distribution. We reasoned that these
      disturbances may be due to the interaction of ApoL9 with
      dioleoylphosphatidylethanolamine (DOPE), the helper lipid component of several
      transfection reagents. Recombinant ApoL9 produced in E. coli, as well as ApoL9
      expressed in HEK293T cells, specifically bind phosphatidylethanolamine (PE) in
      vitro. ApoL9 is expressed at high levels in liver and brain, organs enriched in
      PE. Since PE is known to facilitate replication of positive strand RNA viruses,
      we examined the role of ApoL9 during replication of Japanese encephalitis virus
      (JEV), a positive strand virus of the family Flaviviridae. JEV titres in B16F10L9
      cells are higher than those in B16F10 cells. We propose that ApoL9 is a PE
      binding protein that may have important roles in several cellular processes that
      involve this phospholipid.

PMID- 27697525
TI  - Long-term fructose consumption prolongs hepatic stearoyl-CoA desaturase 1
      activity independent of upstream regulation in rats.
AB  - Dietary fructose is considered a risk factor for metabolic disorders, such as
      fatty liver disease. However, the mechanism underlying the effects of fructose is
      not well characterized. We investigated the hepatic expression of key regulatory
      genes related to lipid metabolism following fructose feeding under well-defined
      conditions. Rats were fed standard chow supplemented with 10% w/v fructose
      solution for 5 weeks, and killed after chow-fasting and fructose withdrawal
      (fasting) or chow-fasting and continued fructose (fructose alone) for 14 h.
      Hepatic deposition of triglycerides was found in rats from both groups. As
      expected, fructose alone increased mRNA levels of lipogenesis-related genes and
      correspondingly decreased mRNA levels of lipid oxidative genes in the liver.
      Interesting, hepatic levels of stearoyl-CoA desaturase (SCD)1 mRNA remained
      elevated under fructose withdrawn conditions, although expression levels of other
      genes, including two key transcription factors (carbohydrate response element
      binding protein (ChREBP) and sterol regulatory element-binding protein (SREBP)
      1c) fell to normal levels, indicating that long-term fructose intake increased
      SCD1 activity, independent of upstream regulatory genes, such as ChREBP and SREBP
      1c. In conclusion, SCD1 overexpression in fatty liver disease is not affected by
      fasting after long-term fructose consumption in rats. Regulation of SCD1 plays an
      important role in fructose-induced hepatic steatosis.

PMID- 27697526
TI  - BCKA down-regulates mTORC2-Akt signal and enhances apoptosis susceptibility in
      cardiomyocytes.
AB  - Diabetic mellitus (DM) portends poor prognosis concerning pressure overloaded
      heart disease. Branched-chain amino acids (BCAAs), elements of essential amino
      acids, have been found altered in its catabolism in diabetes decades ago.
      However, the relationship between BCAAs and DM induced deterioration of pressure
      overloaded heart disease remains controversial. This study is aimed to
      investigate the particular effect of BCKA, a metabolite of BCAA, on myocardial
      injury induced by pressure overloaded. Primary cardiomyocytes were incubated with
      or without BCKA and followed by treatment with isoproterenol (ISO); then cell
      viability was detected by CCK8 and apoptosis was examined by TUNNEL stain and
      caspase-3 activity analysis. Compared to non-BCKA incubated group, BCKA
      incubation decreased cell survival and increased apoptosis concentration
      dependently. Furthermore, Western blot assay showed that mTORC2-Akt pathway was
      significantly inactivated by BCKA incubation. Moreover, overexpression of rictor,
      a vital component of mTORC2, significantly abolished the adverse effects of BCKA
      on apoptosis susceptibility of cardiomyocytes. These results indicate that BCKA
      contribute to vulnerability of cardiomyocytes in stimulated stress via
      inactivation of mTORC2-Akt pathway.

PMID- 27697527
TI  - Discovery of germacrene A synthases in Barnadesia spinosa: The first committed
      step in sesquiterpene lactone biosynthesis in the basal member of the Asteraceae.
AB  - The Andes-endemic Barnadesioideae lineage is the oldest surviving and
      phylogenetically basal subfamily of the Asteraceae (Compositae), a prolific group
      of flowering plants with world-wide distribution (~24,000 species) marked by a
      rich diversity of sesquiterpene lactones (STLs). Intriguingly, there is no
      evidence that members of the Barnadesioideae produce STLs, specialized
      metabolites thought to have contributed to the adaptive success of the Asteraceae
      family outside South America. The biosynthesis of STLs requires the intimate
      expression and functional integration of germacrene A synthase (GAS) and
      germacrene A oxidase (GAO) to sequentially cyclize and oxidize farnesyl
      diphosphate into the advanced intermediate germacrene A acid leading to diverse
      STLs. Our previous discovery of GAO activity conserved across all major
      subfamilies of Asteraceae, including the phylogenetically basal lineage of
      Barnadesioideae, prompted further investigation of the presence of the gateway
      GAS in Barnadesioideae. Herein we isolated two terpene synthases (BsGAS1/BsGAS2)
      from the basal Barnadesia spinosa (Barnadesioideae) that displayed robust GAS
      activity when reconstituted in yeast and characterized in vitro. Despite the
      apparent lack of STLs in the Barnadesioideae, this work unambiguously confirms
      the presence of GAS in the basal genera of the Asteraceae. Phylogenetic analysis
      reveals that the two BsGASs fall into two distinct clades of the Asteraceae's
      GASs, and BsGAS1 clade is only retained in the evolutionary closer Cichorioideae
      subfamily, implicating BsGAS2 is likely the ancestral base of most GASs found in
      the lineages outside the Barnadesioideae. Taken together, these results show the
      enzymatic capacities of GAS and GAO emerged prior to the subsequent radiation of
      STL-producing Asteraceae subfamilies.

PMID- 27697528
TI  - Doxorubicin-induced epithelial-mesenchymal transition through SEMA 4A in
      hepatocellular carcinoma.
AB  - Semaphorins are essential for the functions in the regulation of cell migration.
      SEMA 4A has been proven to play a prominent role in immune function and
      angiogenesis. However, whether SEMA 4A is involved in HCC chemoresistance is
      unclear. We investigated the role of SEMA 4A in HCC chemoresistance and the
      underlying mechanisms. We tested the doxorubicin sensitivity of the Huh7, and Hep
      G2 HCC cell lines. Immunofluorescence and Western blot were used to detect the
      location and expression of EMT-related protein, such as, E-cadherin, Vimentin,
      and SEMA4A expression. Microarray data showed that SEMA 4A and SEMA 3F increased
      most dramatically under DOX treatment. Kncokdown of SEMA 4A in hepatoma cells can
      reduce EMT process. Expectedly, depletion of SEMA 4A also reversed EMT and
      increased the DOX sensitivity. SEMA 4A confers doxorubicin resistance on HCC by
      inducing epithelial-mesenchymal transition (EMT).

PMID- 27697529
TI  - Cox-2 promotes mesenchymal stem cells differentiation into cardiocytes by
      activating JNK and ERK pathway.
AB  - Coronary heart disease and various cardiomyopathys may cause myocardial damage,
      reducing the number of myocardial cells with complete functions. Cyclooxygenase 2
      (Cox-2) has been reported participating in a variety of pathological processes,
      including tumor invasion and metastasis. In this study, we sought to explore the
      correlation of Cox-2 with MSCs proliferation, and migration. MSCs were
      transfected with pcDNA-Cox2 and NS-398 to promote or inhibit the expression of
      Cox2. Then, MTT, transwell, qRT-PCR and western blot were used to test the
      influence of Cox2 on cells proliferation, cells migration and cell viability of
      mesenchymal stem. The results show that Cox-2 promotes directional
      differentiation of myocardial cells and the overexpression of cox-2 can activate
      the key factors of JNK and ERK signaling pathway, promotes myocardial cell
      directional differentiation.

PMID- 27697530
TI  - Identification and characterization of NPC1L1 variants in Uygur and Kazakh with
      extreme low-density lipoprotein cholesterol.
AB  - BACKGROUND: Plasma levels of low-density lipoprotein cholesterol (LDL-C) are a
      major risk factor for cardiovascular disease and are influenced by both heredity
      and dietary habits. The Niemann-Pick C1 like 1 (NPC1L1) protein mediates
      efficient dietary cholesterol absorption and contributes to variations in human
      LDL-C levels. METHODS: In the present study, using high throughput sequencing we
      identified three non-synonymous (NS) variations and 64 synonymous variations in
      the NPC1L1 gene from subsets of Chinese Han, Uygur and Kazakh populations with
      high or low LDL-C. Subsequently, three NS variations encoding R174H, V177I and
      V1284L substitutions were observed only in Uygur and Kazakh individuals with
      limited maximal plasma LDL-C levels. RESULTS: In further experiments, we
      investigated cholesterol-regulated recycling and glycosylation and stability of
      these NS NPC1L1 variants. However, no significant differences between WT and
      variant NPC1L1 proteins were observed using in vivo assays in mouse livers with
      adenovirus-mediated expression, demonstrating that none of the three NPC1L1 NS
      variants caused decreased uptake of biliary cholesterol. CONCLUSIONS:
      Simultaneously, these data indicate that R174H, V177I and V1284L NPC1L1
      variations in high or low LDL-C individuals may not directly influence
      cholesterol absorption by NPC1L1.

PMID- 27697531
TI  - PMEPA1, a TGF-beta- and hypoxia-inducible gene that participates in hypoxic gene
      expression networks in solid tumors.
AB  - Prostate transmembrane protein, androgen induced 1 (PMEPA1) is highly expressed
      in various solid tumors and is known to play important roles in the transforming
      growth factor-beta (TGF-beta) signaling pathway. Here, we demonstrate a novel
      relationship between PMEPA1 and hypoxia, a common microenvironmental stress
      condition in solid tumors. We showed that induction of PMEPA1 expression occurred
      during hypoxia in a manner dependent on both TGF-beta signaling and hypoxia
      inducible factor-1 (HIF-1) pathways. Furthermore, overexpression and knockdown
      experiments revealed that PMEPA1 enhanced HIF-1 transcription activity.
      Bioinformatics analyses of PMEPA1-correlated genes using a gene expression
      database in clinical settings showed significant enrichment of gene sets defined
      by TGF-beta and hypoxia and these two signaling pathways-related angiogenesis and
      epithelial-mesenchymal transition in many types of solid tumors. Collectively,
      our findings indicated that PMEPA1 participates in TGF-beta- and hypoxia
      regulated gene expression networks in solid tumors and thereby may contribute to
      tumor progression.

PMID- 27697532
TI  - PEP-1-SIRT2-induced matrix metalloproteinase-1 and -13 modulates type II collagen
      expression via ERK signaling in rabbit articular chondrocytes.
AB  - Matrix metalloproteinases (MMPs) are critical for the degradation of the
      extracellular matrix (ECM), which includes cartilage-specific collagen types I,
      II and XI. We previously found that PEP-1-sirtuin (SIRT)2 could induce
      dedifferentiation of articular chondrocytes; however, the underlying mechanisms
      remains unclear. We addressed this in the present study by examining the
      association between PEP-1-SIRT2 and the expression of MMP-1 and MMP-13 and type
      II collagen in rabbit articular chondrocytes. We found that PEP-1-SIRT2 increased
      MMP-1 and -13 expression in a dose- and time-dependent manner, as determined by
      western blotting. A similar trend in MMP-1 and -13 levels was observed in
      cultures during expansion to four passages. Pharmacological inhibition of MMP-1
      and -13 blocked the PEP-1-SIRT2-induced decrease in type II collagen level.
      Phosphorylation of extracellular regulated kinase (ERK) was increased by PEP-1
      SIRT2; however, treatment with the mitogen-activated protein kinase inhibitor
      PD98059 suppressed PEP-1-SIRT2-induced MMP-1 and -13 expression and
      dedifferentiation while restoring type II collagen expression in passage 2 cells.
      These results suggest that PEP-1-SIRT2 promotes MMP-induced dedifferentiation via
      ERK signaling in articular chondrocytes.

PMID- 27697533
TI  - Exercise and Hypertension: Uncovering the Mechanisms of Vascular Control.
AB  - Hypertension (HTN) has recently been determined to be the number one overall risk
      factor of disease. With direct and indirect costs amounting to $46.4 billion in
      2011 and projections of six-fold increases by 2030, the importance of low-cost
      nonpharmacological interventions can be appreciated. Vascular structural changes,
      endothelial dysfunction, and sympathetic overstimulation are major contributing
      factors to the pathophysiology of HTN. Exercise training (ET) for blood pressure
      (BP) control has been shown to be an effective and integral component of
      nonpharmacological interventions for BP control. Different ET modalities
      (aerobic, resistance, and concurrent training) have contributed differently to BP
      reduction and control, driving scientific discourse regarding the optimum ET
      prescription (modality, volume, and intensity) for such effects; ET results in a
      multitude of physiological effects, with vascular and autonomic adaptations
      providing major contributions to BP control. Despite widespread acceptance of the
      role and importance of ET for BP reduction, only 15% of US adults have been found
      to meet ET/physical activity recommendations. The purpose of this review is to
      explore BP lowering effects of aerobic and resistance ET and the underlying
      physiological mechanisms that result in such effects. Further research is
      required to enhance our understanding of the proper ET prescription for BP
      control across different age groups and racial ethnicities. Furthermore, research
      into methods of improving awareness and adherence to ET recommendations proves to
      be equally important.

PMID- 27697534
TI  - Emerging roles of the neurotrophin receptor TrkC in synapse organization.
AB  - Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for
      their roles in kinase-dependent signaling cascades in nervous system development.
      Synapse organization is coordinated by trans-synaptic interactions of various
      cell adhesion proteins, a representative example of which is the neurexin
      neuroligin complex. Recently, a novel role for TrkC as a synapse organizing
      protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa
      receptor-type protein tyrosine phosphatase sigma (PTPsigma). TrkC-PTPsigma
      specifically induces excitatory synapses in a kinase domain-independent manner.
      TrkC has distinct extracellular domains for PTPsigma- and NT-3-binding and thus
      may bind both ligands simultaneously. Indeed, NT-3 enhances the TrkC-PTPsigma
      interaction, thus facilitating synapse induction at the pre-synaptic side and
      increasing pre-synaptic vesicle recycling in a kinase-independent fashion. A
      crystal structure study has revealed the detailed structure of the TrkC-PTPsigma
      complex as well as competitive modulation of TrkC-mediated synaptogenesis by
      heparan sulfate proteoglycans (HSPGs), which bind the same domain of TrkC as
      PTPsigma. Thus, there is strong evidence supporting a role for the TrkC-PTPsigma
      complex in mechanisms underlying the fine turning of neural connectivity.
      Furthermore, disruption of the TrkC-PTPsigma complex may be the underlying cause
      of certain psychiatric disorders caused by mutations in the gene encoding TrkC
      (NTRK3), supporting its role in cognitive functions.

PMID- 27697536
TI  - Association of serum high-sensitivity C-reactive protein with metabolic control
      and diabetic chronic vascular complications in patients with type 2 diabetes.
AB  - AIMS: To determine an association between hs-CRP and metabolic control/diabetic
      chronic vascular complications (DCVCCxs) in the patients with type 2 diabetes
      (DM). In addition, the possibility of using hs-CRP levels to predict risk of
      DCVCCxs will also be validated. METHODS: This cohort study randomly enrolled 608
      patients with DM during the 2007-2008 study period. We also recorded basic
      laboratory findings at baseline and at one year, to include fasting plasma
      glucose, HbA1c, triglyceride, total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, and hs-CRP. RESULTS: Logistic
      regressions of odds ratios between hs-CRP and DCVCCxs (coronary arterial disease,
      cerebrovascular disease, diabetic nephropathy, diabetic retinopathy, and diabetic
      peripheral neuropathy) showed significant correlations, except for
      cerebrovascular disease, as follows 0.2 (0.11-0.38), 0.09 (0.01-0.77), 0.06 (0.02
      0.16), 0.31 (0.12-0.82), and 0.17 (0.07-0.43), respectively. Linear regression
      for changes in hs-CRP were significantly correlated with HbA1c (r=0.38), fasting
      plasma glucose (r=0.40), triglyceride (r=0.20), low-density lipoprotein
      cholesterol (r=0.12), and high-density lipoprotein cholesterol (r=-0.12). No
      correlation was found for total cholesterol (r=0.06). Based on receiver operating
      characteristic (ROC) analysis, the cut-off points for hs-CRP levels for
      prediction of DCVCCxs were 2.89, 2.25, 2.10, 2.25, and 2.82mg/L, for coronary
      arterial disease, cerebrovascular disease, diabetic nephropathy, diabetic
      retinopathy, and diabetic peripheral neuropathy, respectively. CONCLUSIONS: Our
      data showed that DCVCCxs were associated with hs-CRP in patients with DM. The cut
      off point for hs-CRP can be used to predict association with DCVCCxs. Well
      controlled metabolic components in diabetic patients, especially HbA1c, fasting
      plasma glucose, and triglyceride may reduce the level of hs-CRP.

PMID- 27697535
TI  - Levels of physical activity are correlated with intima media ratio in subjects
      without but not with metabolic syndrome: A study of Iranians without a history of
      cardiovascular events.
AB  - AIM: We aimed to investigate the relationship between carotid Intima Media
      Thickness (CIMT) and physical activity levels (PAL), in subjects with and without
      metabolic syndrome (MetS) and in indidiviuals with and without carotid artery
      plaque (CAP) defined using high-resolution ultrasound. METHOD: A sample of 506
      subjects [215 (42.5%) males], aged 35-64 years was recruited from an urban
      population in Mashhad, Iran, using a stratified-cluster method as part of the
      Mashhad Stroke Heart Atherosclerosis Disorder (MASHAD) study cohort. This sub
      sample was selected randomly from a cohort of 9765 individuals for carotid duplex
      ultrasound. Comparisons were made between individuals with and without CAP on the
      one hand, and between participants with and without MetS on the other hand with
      regard to physical activity and cardiometabolic risk level, as well as their
      correlation with CIMT. RESULT: PAL was positively and significantly correlated
      with CIMT in the total sample (r=0.132, p<0.001). The correlation coefficient was
      0.132 (p=0.426) in the MetS+ participants and 0.440 (p<0.001) in the MetS-
      participants. The correlation of PAL with CIMT was also positive and significant
      in CAP+ participants (r=0.150, p<0.001), but not in the CAP- participants (r=
      0.001, p=0.621), with however a non-significant difference between the two
      estimates (p=0.374). Hip circumference was correlated with CIMT in MetS- but not
      MetS+ participants. CONCLUSION: physical activity in the current study appeared
      to be a correlate of infraclinical CVD risk in participants without metabolic
      syndrome, but not in those without.

PMID- 27697537
TI  - Macrophages are essential for maintaining a M2 protective response early after
      ischemic brain injury.
AB  - Resident microglia and recruited macrophages are major contributors to the post
      ischemic inflammatory response. Initially considered functionally homogeneous
      populations, data now suggest distinct but still controversial roles after brain
      injury. Using a model of conditional monocyte/macrophage depletion we studied the
      contribution of these myeloid cells to brain lesion progression after ischemia,
      and their influence on the ischemic inflammatory environment. Male CD11b-DTR
      transgenic mice, expressing the human diphtheria toxin receptor under the control
      of the CD11b promoter, were treated with diphtheria toxin to induce
      monocyte/macrophage depletion. Twenty four hours later the middle cerebral artery
      was permanently occluded. The ischemic lesion was measured 24h after injury. At
      the same time microglia and macrophage activation and polarization were assessed
      by quantitative immunohistochemistry and confocal microscopy for CD45high, CD11b,
      CD68, CD16/32, iNOS, Arg1, Ym1, and CD206, and gene expression was investigated
      on CD11b+ sorted cells. Depletion of monocytes/macrophages worsened the ischemic
      lesion within 24h after the ischemic insult. This effect was associated with
      higher M1/M2 polarization ratio in the ischemic lesion. Moreover, depletion
      increased the expression of M1 phenotypic markers on CD11b positive cells. Gene
      expression on CD11b+ sorted cells indicated a selective increase of iNOS and
      lower Arg1 mRNA expression than in non depleted mice. Depletion of
      monocytes/macrophages increases the ischemic lesion, an effect accompanied by an
      increase in the M1/M2 polarization ratio of microglia and macrophages in the
      ischemic area. Thus in ischemic injury recruited monocytes/macrophages may
      control an excessive M1 pro-inflammatory response, suggesting their ability to
      drive M2 protective polarization.

PMID- 27697538
TI  - Relationships of comorbidities and old age with postoperative complications of
      head and neck free flaps: A review.
AB  - The aim of this study was to determine the relationships between free flap
      complications and old age or comorbidities. In a PubMed and Scopus search, the
      search terms (1) free flap OR microvascular anastomosis AND (2) elderly OR old
      age AND (3) complications OR comorbidity OR co-morbidity were used. Among the 62
      full-text articles from 241 abstracts, 31 papers without sufficient content were
      excluded and 10 mined papers were added. Subsequently, 41 papers were reviewed.
      Overall complication rates of free flap increased significantly with age (p <
      0.001; y = 0.457x + 13.464; 40.9% at 60 years, 45.5% at 70 years, and 50.0% at 80
      years). Flap survival rates increased significantly (p < 0.001; y = 0.025x +
      93.876). Donor site complication rates also increased significantly with age (p <
      0.001; y = 1.238x - 63.700; 10.9% at 60 years, 23.0% at 70 years, and 35.3% at 80
      years). The Kaplan-Feinstein index (KFI, OR = 7.944, 9.563), the Adult
      Comorbidity Evaluation-27 (ACE-27, OR = 5.854), the American Society of
      Anesthesiologists score (ASA, OR = 4.397), and the Index of Coexistent Diseases
      score (ICED, OR = 3.584) had statistically significant impacts on flap survival
      (p < 0.05). Diabetes (OR = 4.562) and chronic obstructive pulmonary disease (OR =
      2.300) had statistically significant negative impacts on the flap survival rate
      (p < 0.05). Elderly patients had significantly higher Charlson Comorbidity Index
      (CCI) and ASA scores (p < 0.001). Similarly, elderly patients exhibited a
      significantly higher prevalence of dementia (p < 0.001) and use of aspirin at the
      time of surgery (p < 0.001). On the basis of these results, we suggest that the
      incidence of complications is directly related to the preoperative medical
      condition of an individual patient rather than to age.

PMID- 27697539
TI  - Development of a decellularization method to produce nerve allografts using less
      invasive detergents and hyper/hypotonic solutions.
AB  - BACKGROUND: Here, we describe a novel method of processing decellularized nerve
      grafts using osmotic effects of hypotonic and hypertonic solutions and Triton X
      100 (a nonionic detergent) and CHAPS (an amphoteric detergent). MATERIALS AND
      METHODS: To evaluate decellularization, the devised method and Hudson's method
      were compared with respect to remaining cellular components (as assessed by H&E
      staining and S-100 immunoreactivity) and extracellular matrix structural
      integrity (as assessed by H&E staining and laminin immunoreactivity) by using rat
      sciatic nerves. In addition, a 1.5-cm sciatic nerve gap rat model was treated by
      implanting decellularized nerve grafts prepared using the devised method,
      Hudson's method, or an autograft to evaluate nerve regeneration. Nerve
      histomorphometry of distal stumps and wet muscle mass were evaluated at 12 weeks
      after implantation. RESULTS: The devised method produced outcomes similar to
      those of Hudson's method in terms of cellular component removal, but the devised
      method was significantly better in terms of ECM preservation. Histomorphometric
      study showed that the devised method produced significantly fewer nerve fiber and
      axonal densities than autografting, but much more than Hudson's method. The wet
      muscle mass of the devised method was also significantly lower than that of
      autografting, but much higher than that of Hudson's method. CONCLUSION: The
      described process for producing decellularized nerve grafts yielded better
      outcomes with respect to peripheral nerve regeneration than the established ionic
      detergent-based methods in a rat model. This study indicates that decellularized
      nerve grafts produced in this manner show favorable nerve regeneration used for
      bridging nerve gaps.

PMID- 27697540
TI  - Harmful effects behind the daily supplementation of a fixed vegetarian blend in
      the rat model.
AB  - Fruit and vegetables (FV) have long been considered a panacea against major
      chronic diseases, including cancer. However, there is no convincing
      epidemiological, clinical or experimental evidence supporting FV chemopreventive
      ability. A daily mono-supplementation of lyophilized onion, tomato, peach, black
      grape or lettuce was compared with the daily combined administration of the same
      FV (5 a day-like diet). Ten days post-treatment, the phase-I/II xenobiotic
      metabolizing and antioxidant enzyme activities, protein and mRNA levels were
      investigated. As a marker of oxidative stress, the level of hydroperoxides was
      measured in rat serum samples. Here we show that a blend of FV orally
      administered to rats not only potentially manipulates metabolism but also
      disrupts systemic oxidative homeostasis. A daily combination of the five servings
      remarkably down-regulates the catalytic activity, protein and mRNA levels of a
      cohort of hepatic metabolizing enzymes, suggesting a possible depressed clearance
      upon exposure to ubiquitous carcinogens. Strikingly, we observed an impairment of
      antioxidant enzymes with a boost in systemic hydroperoxide levels. Our study
      identifies new potential factors of cancer risk connected with the persistent
      consumption of fixed servings of FV, suggesting that dietary guidance should rely
      on a "daily diversification" of FV.

PMID- 27697541
TI  - RIFM fragrance ingredient safety assessment, ethylene brassylate, CAS Registry
      Number 105-95-3.
AB  - : The use of this material under current conditions is supported by existing
      information. This material was evaluated for genotoxicity, repeated dose
      toxicity, developmental and reproductive toxicity, local respiratory toxicity,
      phototoxicity/photoallergenicity, skin sensitization, as well as environmental
      safety. Data show that this material is not genotoxic nor does it have skin
      sensitization potential. The local respiratory toxicity endpoint was completed
      using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material
      (1.4 mg/day). The repeated dose toxicity endpoint was completed using ethylene
      dodecanedioate (CAS # 54982-83-1) as a suitable read across analog, which
      provided a MOE > 100. The developmental and reproductive toxicity endpoint was
      completed using oxacyclohexadec-12-en-2-one, (12E)- (CAS # 111879-80-2) as a
      suitable read across analog, which provided a MOE > 100. The
      phototoxicity/photoallergenicity endpoint was completed based on suitable UV
      spectra along with data on the target material. The environmental endpoint was
      completed as described in the RIFM Framework along with data on the suitable read
      across analog oxacyclohexadec-12-en-2-one, (12E)- (CAS # 111879-80-2).

PMID- 27697544
TI  - Gadolinium deposition: Is it chelated or dissociated gadolinium? How can we tell?
AB  - The methodology and published work aimed at speciation of gadolinium based
      contrast agents in tissues is reviewed. The discussion focusses on the context of
      Gd deposited long term in tissue following administration of the contrast agents.
      Detection of Gd without identification of the chemical form detected is simple
      and straight forward using a variety of methods. Determination of the chemical
      form of Gd detected is far more complex and most methods require inherently
      imperfect extraction steps that can alter the Gd chemical species detected.
      Control studies wherein Gd is not deposited biologically or is deposited in
      animal tissues are also inherently imperfect. Strengths and weaknesses of the
      various methods used and examples are demonstrated. It is concluded that a
      combination of spatially resolved mass spectral based methods, combined with
      extraction/HPLC analysis methods can provide sufficient sensitivity, spatial
      resolution and chemical species specificity to address the title question on ex
      vivo tissue samples.

PMID- 27697542
TI  - RIFM fragrance ingredient safety assessment, 1,3,3-trimethyl-2-norbornanyl
      acetate, CAS registry number 13851-11-1.

PMID- 27697543
TI  - Hemorheological characteristics of red blood cells exposed to surface
      functionalized graphene quantum dots.
AB  - Graphene quantum dots (GQDs) are potential candidates for various biomedical
      applications such as drug delivery, bioimaging, cell labeling, and biosensors.
      However, toxicological information on their effects on red blood cells (RBCs) and
      the mechanisms involved remain unexplored. To the best of our knowledge, our
      study is the first to investigate the toxicity effects of three GQDs with
      different surface functionalizations on the hemorheological characteristics of
      human RBCs, including hemolysis, deformability, aggregation, and morphological
      changes. RBCs were exposed to three different forms of GQDs (non-functionalized,
      hydroxylated, and carboxylated GQDs) at various concentrations (0, 500, 750, and
      1000 MUg/mL) and incubation times (0, 1, 2, 3, or 4 h). The rheological
      characteristics of the RBCs were measured using microfluidic-laser diffractometry
      and aggregometry. Overall, the hemolysis rate and rheological alterations of the
      RBCs were insignificant at a concentration less than 500 MUg/mL. Carboxylated
      GQDs were observed to have more substantial hemolytic activity and caused abrupt
      changes in the deformability and aggregation of the RBCs than the non
      functionalized or hydroxylated GQDs at concentrations >750 MUg/mL. Our findings
      indicate that hemorheological assessments could be utilized to estimate the
      degree of toxicity to cells and to obtain useful information on safety sheets for
      nanomaterials.

PMID- 27697545
TI  - Antivirals against animal viruses.
AB  - Antivirals are compounds used since the 1960s that can interfere with viral
      development. Some of these antivirals can be isolated from a variety of sources,
      such as animals, plants, bacteria or fungi, while others must be obtained by
      chemical synthesis, either designed or random. Antivirals display a variety of
      mechanisms of action, and while some of them enhance the animal immune system,
      others block a specific enzyme or a particular step in the viral replication
      cycle. As viruses are mandatory intracellular parasites that use the host's
      cellular machinery to survive and multiply, it is essential that antivirals do
      not harm the host. In addition, viruses are continually developing new antiviral
      resistant strains, due to their high mutation rate, which makes it mandatory to
      continually search for, or develop, new antiviral compounds. This review
      describes natural and synthetic antivirals in chronological order, with an
      emphasis on natural compounds, even when their mechanisms of action are not
      completely understood, that could serve as the basis for future development of
      novel and/or complementary antiviral treatments.

PMID- 27697547
TI  - Neuromuscular contributions to the age-related reduction in muscle power:
      Mechanisms and potential role of high velocity power training.
AB  - Although much of the literature on neuromuscular changes with aging has focused
      on loss of muscle mass and isometric strength, deficits in muscle power are more
      pronounced with aging and may be a more sensitive measure of neuromuscular
      degeneration. This review aims to identify the adaptations to the neuromuscular
      system with aging, with specific emphasis on changes that result in decreased
      muscle power. We discuss how these changes in neuromuscular performance can
      affect mobility, and ultimately contribute to an increased risk for falls in
      older adults. Finally, we evaluate the literature regarding high-velocity muscle
      power training (PT), and its potential advantages over conventional strength
      training for improving functional performance and mitigating fall risk in older
      adults.

PMID- 27697546
TI  - Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative
      diseases: An aging effect.
AB  - Current understanding on the mechanisms of brain injury and neurodegeneration
      highlights an appreciation of multicellular interactions within the neurovascular
      unit (NVU), which include the evolution of blood-brain barrier (BBB) damage,
      neuronal cell death or degeneration, glial reaction, and immune cell
      infiltration. Aging is an important factor that influences the integrity of the
      NVU. The age-related physiological or pathological changes in the cellular
      components of the NVU have been shown to increase the vulnerability of the NVU to
      ischemia/reperfusion injury or neurodegeneration, and to result in deteriorated
      brain damage. This review describes the impacts of aging on each NVU component
      and discusses the mechanisms by which aging increases NVU sensitivity to stroke
      and neurodegenerative diseases. Prophylactic or therapeutic perspectives that may
      delay or diminish aging and thus prevent the incidence of these neurological
      disorders will also be reviewed.

PMID- 27697549
TI  - A human cellular system for analyzing signaling during corneal endothelial
      barrier dysfunction.
AB  - Correct corneal endothelial barrier function is essential for maintaining corneal
      transparency. However, research on cell signaling pathways mediating corneal
      endothelial barrier dysfunction has progressed more slowly than that involving
      other cellular barriers because of the lack of human corneal endothelial cell
      models. Here we have optimized the culture of the human corneal endothelial cell
      (HCEC) line B4G12 as a model for studying paracellular permeability. We show that
      B4G12-HCECs form confluent monolayers with stable cell-cell junctions when
      cultured on plastic, but not glass, surfaces precoated with various extracellular
      matrix components. Cell morphometry and measuring intercellular spaces and
      transendothelial electric resistance indicate that B4G12-HCECs form optimal
      monolayers on collagen and fibronectin. Based on the use of specific inhibitors,
      it has been proposed that the Rho-regulated kinases, ROCK-I and ROCK-II, mediate
      actomyosin-induced contraction in corneal endothelial cell barriers. ROCKs are
      effectors of RhoA, RhoB and RhoC. We show that the GTPase RhoA and its effector
      ROCK-II are predominantly expressed in B4G12-HCECs and primary human corneal
      endothelial cells. The activation of Rho GTPases during acute barrier disruption
      has not been investigated in corneal endothelial cells. RhoA, but not other
      related GTPases that are highly expressed in B4G12-HCECs, such as Rac1 and Cdc42,
      is transiently activated during barrier disruption in response to the
      inflammatory mediator thrombin. Pharmacological inhibition of RhoA and ROCK
      reduces B4G12-HCEC acute contraction. We propose that exploiting B4G12-HCECs is a
      useful experimental strategy for gaining further insight into the signaling
      pathways involved in human corneal endothelial barrier function.

PMID- 27697548
TI  - Alteration in cellular turnover and progenitor cell population in lacrimal glands
      from thrombospondin 1-/- mice, a model of dry eye.
AB  - The purpose of this study was to investigate the changes that occur in the
      lacrimal glands (LGs) in female thrombospondin 1 knockout (TSP1-/-) mice, a mouse
      model of the autoimmune disease Sjogren's syndrome. The LGs of 4, 12, and 24 week
      old female TSP1-/- and C57BL/6J (wild type, WT) mice were used. qPCR was
      performed to measure cytokine expression. To study the architecture, LG sections
      were stained with hematoxylin and eosin. Cell proliferation was measured using
      bromo-deoxyuridine and immunohistochemistry. Amount of CD47 and stem cell markers
      was analyzed by western blot analysis and location by immunofluorescence
      microscopy. Expression of stem cell transcription factors was performed using
      Mouse Stem Cell Transcription Factors RT2 Profiler PCR Array. Cytokine levels
      significantly increased in LGs of 24 week-old TSP1-/- mice while morphological
      changes were detected at 12 weeks. Proliferation was decreased in 12 week-old
      TSP1-/- mice. Three transcription factors were overexpressed and eleven
      underexpressed in TSP1-/- compared to WT LGs. The amount of CD47, Musashi1, and
      Sox2 was decreased while the amount of ABCG2 was increased in 12 week-old TSP1-/-
      mice. We conclude that TSP1 is necessary for maintaining normal LG homeostasis.
      Absence of TSP1 alters cytokine levels and stem cell transcription factors, LG
      cellular architecture, decreases cell proliferation, and alters amount of stem
      cell markers.

PMID- 27697550
TI  - The cold driver: Cold stress while driving results in dangerous behavior.
AB  - Cool vehicle cabin temperatures can induce short-term non-hypothermic cold
      stress. The current study created a cold condition to examine the impact of cold
      stress on driving behavior. Forty-four participants drove a high-fidelity driving
      simulator during a thermal neutral or local torso cooled condition. Participants
      performed additional tasks to assess attention, psychomotor vigilance, and manual
      dexterity. Skin temperature was significantly lower in the cold condition while
      internal temperature was unaffected. Participants who had higher subjective
      ratings of cold followed lead vehicles closer and started to brake later.
      Participants in the cold condition followed the lead car 22% (0.82s) closer and
      started braking 20% (2.35s) later when approaching a stop sign during the car
      following task. No change in attention, psychomotor vigilance, or dexterity was
      observed. The current results suggest that cold environmental conditions can
      contribute to dangerous driving behaviors. Measures of cold perception were also
      shown to predict changes in driving behavior.

PMID- 27697551
TI  - Frontal EEG theta/beta ratio as an electrophysiological marker for attentional
      control and its test-retest reliability.
AB  - A robust finding is that resting-state frontal theta/beta ratio (TBR), a
      spontaneous electroencephalographic (EEG) frequency band parameter, is increased
      in attention-deficit/hyperactivity disorder. Accumulating evidence suggests that
      TBR might also provide an objective marker of executive cognitive control (and
      more specifically attentional control; AC) in healthy adults. The present study
      aimed to further investigate this conception by assessing EEG frequency band
      power and AC twice (with a one-week interval) in 41 young female adults. In line
      with our predictions, the negative association between TBR and trait AC, as
      measured with an often used self-report measure, was replicated. Results also
      demonstrated that test-retest reliability of resting-state frontal TBR was very
      good (r=.93) and, moreover, TBR measured at the first session predicted AC during
      the second session (r=-.44). These consistent results further reinforce the
      notion that frontal TBR could be used as a reliable biomarker for prefrontally
      mediated executive AC.

PMID- 27697552
TI  - Driving performance and EEG fluctuations during on-the-road driving following
      sleep deprivation.
AB  - The present study mainly aimed to assess whether and how sleepiness due to sleep
      deprivation interacts with Time on Task (ToT) effects both on
      electroencephalography (EEG) measures and driving performance in real driving
      conditions. Healthy participants performed a one hour on-the-road monotonous
      highway driving task while EEG was recorded continuously after one night of
      normal sleep and after one night of total sleep deprivation. The main outcome
      parameter in the highway driving test was the Standard Deviation of Lateral
      Position (SDLP). SDLP and EEG indices (i.e alpha and theta power spectra)
      increased after sleep deprivation and varied with ToT. The latter was more
      pronounced after sleep deprivation. Beta power spectra did not differ between
      conditions but increased with ToT. Changes in SDLP and EEG did not correlate
      significantly. We conclude that driving performance as well as fatigue and
      sleepiness fluctuations with ToT were more evident after sleep deprivation as
      compared to normal sleep.

PMID- 27697553
TI  - Acute buspirone dosing enhances abuse-related subjective effects of oral
      methamphetamine.
AB  - There is not an approved pharmacotherapy for treating methamphetamine use
      disorder. This study sought to determine the effects of acute buspirone treatment
      on the subjective and cardiovascular effects of oral methamphetamine in order to
      provide an initial assessment of the utility, safety, and tolerability of
      buspirone for managing methamphetamine use disorder. We predicted that acute
      buspirone administration would reduce the subjective effects of methamphetamine.
      We also predicted that the combination of buspirone and methamphetamine would be
      safe and well tolerated. Ten subjects completed the protocol, which tested three
      methamphetamine doses (0, 15, and 30mg) in combination with two buspirone doses
      (0 and 30mg) across 6 experimental sessions. Subjective effects and physiological
      measures were collected at regular intervals prior to and after dose
      administration. Methamphetamine produced prototypical subjective and
      cardiovascular effects. Acute buspirone administration increased some of the
      abuse-related subjective effects of methamphetamine and also attenuated some
      cardiovascular effects. The combination of oral methamphetamine and buspirone was
      safe and well tolerated. Acute buspirone administration may increase the abuse
      liability of oral methamphetamine. Chronic buspirone dosing studies remain to be
      conducted, but given preclinical findings and the outcomes of this work, the
      utility of buspirone for treating methamphetamine use disorder appears limited.

PMID- 27697555
TI  - Transition from ethanol-induced sensitization to tolerance across early and late
      infancy in the rat.
AB  - Drugs of abuse, as cocaine or amphetamine, induce locomotor sensitization during
      infancy and adulthood of the rat. This effect during the preweanling period is
      observed only after a short interval of time between training and testing. We
      recently reported short-term locomotor sensitization induced by ethanol in pups
      chronically exposed to the drug during the second postnatal week of life. The
      present series of experiments was designed to explore the persistence of the
      sensitization effect across the preweanling period. Pups were chronically exposed
      to ethanol in five consecutive days during the second or the third postnatal
      weeks, and their locomotor activity was evaluated in an open field 3, 8 or 15days
      later. Our results showed that, contrarily to what has been observed with other
      drugs during infancy, sensitization to ethanol persisted at least 8days in rats
      exposed to the drug during the second postnatal week. Surprisingly, in older
      pups, the same procedure induced tolerance instead sensitization. This
      ontogenetic model offers a potentially interesting tool for studying within the
      same species, how tolerance and sensitization are interrelated, and how these
      effects affect ethanol-mediated reinforcement and ethanol intake during ontogeny.

PMID- 27697556
TI  - Multiple colonisations of the Lake Malawi catchment by the genus Opsaridium
      (Teleostei: Cyprinidae).
AB  - It has been proposed that the fish faunas of African rivers assemble through
      multiple colonisation events, while lake faunas form additionally through
      intralacustine speciation. While this pattern has been established for many
      lineages, most notably cichlids, there are opportunities to further investigate
      the concept using phylogenies of congeneric endemic species within ancient lake
      catchments. The Lake Malawi catchment contains three river-spawning cyprinids of
      the genus Opsaridium, two of which are endemic. These species differ in body
      size, migratory behaviour and habitat use, but it has never previously been
      tested if these represent a monophyletic radiation, or have instead colonised the
      lake independently. We placed these species in a broader phylogeny of Opsaridium
      and the related genus Raiamas, including all known species from the river systems
      surrounding Lake Malawi. Our results suggest that each of the species has
      independently colonised the lake catchment, with all three taxa having well
      defined sister taxa outside of the lake, and all sharing a common ancestor
      ~14.9million years ago, before the Lake Malawi basin started to form ~8.6million
      years ago. Additionally, the results strongly support previous observations that
      Opsaridium is not a monophyletic group, but instead contains Raiamas from the
      Congo drainage. Together these results are supportive of the concept that river
      fish faunas within African catchments are primarily assembled through a process
      of accumulation from independent origins, rather than within-catchment speciation
      and adaptive radiation. In light of these results we also suggest there is scope
      for a re-evaluation of systematics of both Opsaridium and Raiamas.

PMID- 27697554
TI  - Efficacy of an adenovirus-based anti-cocaine vaccine to reduce cocaine self
      administration and reacqusition using a choice procedure in rhesus macaques.
AB  - Immunopharmacotherapy offers an approach for treating cocaine abuse by
      specifically targeting the cocaine molecule and preventing its access to the CNS.
      dAd5GNE is a novel cocaine vaccine that attenuates the stimulant and the
      reinforcing effects of cocaine in rats. The goal of this study was to extend and
      validate dAd5GNE vaccine efficacy in non-human primates. Six experimentally naive
      adult female rhesus monkeys (Macaca mulatta) were trained to self-administer
      0.1mg/kg/injection intravenous (i.v.) cocaine or receive candy; then 4 monkeys
      were administered the vaccine and 2 monkeys were administered vehicle
      intramuscularly, with additional vaccine boosts throughout the study. The
      reinforcing effects of cocaine were measured during self-administration,
      extinction, and reacquisition (relapse) phases. Serum antibody titers in the
      vaccinated monkeys remained high throughout the study. There was no change in the
      preference for cocaine over candy over a 20-week period in 5 of the 6 monkeys;
      only one of the 4 (25%) vaccinated monkeys showed a decrease in cocaine choice.
      All 6 monkeys extinguished responding for cocaine during saline extinction
      testing; vaccinated monkeys tended to take longer to extinguish responding than
      control monkeys (17.5 vs. 7.0 sessions). Vaccination substantially retarded
      reacquisition of cocaine self-administration; control monkeys resumed cocaine
      self-administration within 6-41 sessions and 1 vaccinated monkey resumed cocaine
      self-administration in 19 sessions. The other 3 vaccinated monkeys required
      between 57 and 94 sessions to resume cocaine self-administration even in the
      context of employing several manipulations to encourage cocaine reacquisition.
      These data suggest that the dAdGNE vaccine may have therapeutic potential for
      humans who achieve cocaine abstinence as part of a relapse prevention strategy.

PMID- 27697557
TI  - DNA shuffling approach for recombinant polyvalent OmpAs against V. alginolyticus
      and E. tarda infections.
AB  - Molecular breeding via DNA shuffling directs the evolution of vaccines with
      desired traits. In the present study, polyvalent OmpA vaccines were generated by
      DNA shuffling of five ompA genes from four species of bacteria Vibrio
      parahaemolyticus, V. alginolyticus, Edwardsiella tarda and Escherichia coli.
      First, a new hybrid OmpA was constructed using VA0764 primers and used for
      construction of a prokaryotic expressing library PompAs-FV containing 84 ompAs,
      which were validated by PCR and SDS/PAGE. Then, the 84 ompAs were used to
      construct a eukaryotic expressing library EompAs-FV for preparing DNA vaccines.
      Third, extracellular bacterium V. alginolyticus challenge post active
      immunization using these DNA vaccines was carried out to identify genes with high
      immunoprotection. Among the 84 ompAs, 17 showed higher or equal immune protection
      against infection caused by V. alginolyticus than control VA0764. Finally, immune
      protection against infection caused by intracellular bacterium Edwardsiella tarda
      was assessed further using the top seven out of the 17 ompAs. This led to
      identification of three efficient polyvalent vaccines against infections caused
      by the extracellular bacterium V. alginolyticus and intracellular bacterium E.
      tarda. In addition, we sequenced genes for understanding mechanisms of the
      polyvalent vaccines, but association of immune protection with mutation of gene
      and amino acids is not determined. These results indicate that DNA shuffling is
      an efficient way to develop polyvalent vaccines against microbial infections.

PMID- 27697558
TI  - Changes in the levels of humoral immune activities after storage of gilthead
      seabream (Sparus aurata) skin mucus.
AB  - Skin mucus is increasingly used as a source for determining immunity-related
      proteins and enzymes. However, the ability to accurately measure some activities
      may be modified by inadequate handling and storage of the samples. This study
      aims to measure the effect of freezing and lyophilization at the time of
      collection on such activities. Fresh, frozen (immediately after collection at -20
      degrees C and -80  degrees C) and lyophilized skin mucus samples obtained from
      the same groups of fish specimens of gilthead seabream (Sparus aurata L.) were
      analysed in the assays. The amount of total proteins and sugar residues
      (determined by lectin binding) present in skin mucus samples fell after both
      freezing and lyophilization of the samples. While no significant differences were
      exhibited in the levels of some proteins or enzymes (immunoglobulin M,
      antiprotease, peroxidase, esterase and alkaline phosphatase) determined in fresh
      or frozen mucus samples, protease and lysozyme activities were lower in frozen
      mucus samples than in fresh samples. Lyophilization of the mucus samples
      drastically decreased the total level of proteins obtained, as well as of
      protease, peroxidase, lysozyme and alkaline phosphatase activities. The results
      suggest that freezing skin mucus samples is more suitable than lyophilization if
      samples are stored before determining enzymatic activities.

PMID- 27697559
TI  - Polymorphism in a serine protease inhibitor gene and its association with the
      resistance of bay scallop (Argopecten irradians) to Listonella anguillarum
      challenge.
AB  - Serine protease inhibitors (SPIs) play a crucial role in regulation of both host
      and bacterial serine protease. They are classified into several protein families,
      where Kazal-type inhibitors are one of families with multi-domain. In the present
      study, the polymorphism of AiSPI from Bay scallop Argopecten irradians was found
      to be associated with disease resistance of bay scallop against Listonella
      anguillarum. Nine single nucleotide polymorphisms (SNPs) were identified in the
      exon region of AiSPI, where five SNPs were non-synonymous mutation. Three of
      these mutations were located in "kazal-like 3"domain, two SNP loci positioned at
      +536, +1312 were selected for further association studies. For the locus +536,
      the genotype frequency of A/G in the resistant stock (12.8%) was significantly
      lower (p < 0.05) than that in the susceptible stock (35.1%), while, the genotype
      A/A in the resistant stock (87.2%) was significantly higher in comparison with
      susceptible stock (64.9%) (p < 0.05). The G allele frequencies were 6.4% and
      17.6% in resistant stock and susceptible stock, respectively, and chi2-test
      revealed a significant difference in the frequency distribution between the two
      stocks (p < 0.05). But there was no significant association between the mutation
      C-T at locus +1312 with either resistant or susceptible group (p > 0.05). The
      genotype frequencies of T/T, T/C, C/C at locus +1312 were 94.6%, 2.7% and 2.7%
      respectively in the susceptible stock, while 100%, 0% and 0% respectively in the
      resistant stock. The amino acid change for the mutation at locus +536 A-G was
      from asparagine to serine, and the predicted homology model of this amino acid
      variation could affect its function as well as the structural integrity of the
      domain. In vitro elastase inhibition assay of the protein variants at locus +536
      was conducted to explicate the effect of SNP. The increasing concentration of
      protein (0 mmol/L- 2.93 mmol/L) was incubated with 80 nmol/L elastase where the
      residual enzyme activity values for rAiSPI (N) with A variant and rAiSPI (S) with
      G variant were started to reduce from 0.40 to 0.215 and 0.435 to 0.356,
      respectively. The elastase inhibition ability of rAiSPI (N) variant was
      significantly higher than that of rAiSPI (S) (p < 0.01). The results suggested
      that the mutation at locus +536A/A significantly associated with disease
      resistance of bay scallop would shed light for selective breeding program.

PMID- 27697560
TI  - Genomic structure and expression pattern of MHC IIalpha and IIbeta genes reveal
      an unusual immune trait in lined seahorse Hippocampus erectus.
AB  - The major histocompatibility complex (MHC) genes are crucial in the adaptive
      immune system, and the gene duplication of MHC in animals can generally result in
      immune flexibility. In this study, we found that the lined seahorse (Hippocampus
      erectus) has only one gene copy number (GCN) of MHC IIalpha and IIbeta, which is
      different from that in other teleosts. Together with the lack of spleen and gut
      associated lymphatic tissue (GALT), the seahorse may be referred to as having a
      partial but natural "immunodeficiency". Highly variable amino acid residues were
      found in the IIalpha and IIbeta domains, especially in the alpha1 and beta1
      domains with 9.62% and 8.43% allelic variation, respectively. Site models
      revealed seven and ten positively selected positions in the alpha1 and beta1
      domains, respectively. Real-time PCR experiments showed high expression levels of
      the MHC II genes in intestine (In), gill (Gi) and trunk kidney (TK) and medium in
      muscle (Mu) and brood pouch (BP), and the expression levels were significantly up
      regulated after bacterial infection. Specially, relative higher expression level
      of both MHC IIalpha and IIbeta was found in Mu and BP when compared with other
      fish species, in which MHC II is expressed negligibly in Mu. These results
      indicate that apart from TK, Gi and In, MU and BP play an important role in the
      immune response against pathogens in the seahorse. In conclusion, high allelic
      variation and strong positive selection in PBR and relative higher expression in
      MU and BP are speculated to partly compensate for the immunodeficiency.

PMID- 27697561
TI  - Structural Insight into Recognition of Methylated Histone H3K4 by Set3.
AB  - The plant homeodomain (PHD) finger of Set3 binds methylated lysine 4 of histone
      H3 in vitro and in vivo; however, precise selectivity of this domain has not been
      fully characterized. Here, we explore the determinants of methyllysine
      recognition by the PHD fingers of Set3 and its orthologs. We use X-ray
      crystallographic and spectroscopic approaches to show that the Set3 PHD finger
      binds di- and trimethylated states of H3K4 with comparable affinities and employs
      similar molecular mechanisms to form complexes with either mark. Composition of
      the methyllysine-binding pocket plays an essential role in determining the
      selectivity of the PHD fingers. The finding that the histone-binding activity is
      not conserved in the PHD finger of Set4 suggests different functions for the Set3
      and Set4 paralogs.

PMID- 27697562
TI  - Engineering nonphosphorylative metabolism to synthesize mesaconate from
      lignocellulosic sugars in Escherichia coli.
AB  - Dicarboxylic acids are attractive biosynthetic targets due to their broad
      applications and their challenging manufacturing process from fossil fuel
      feedstock. Mesaconate is a branched, unsaturated dicarboxylic acid that can be
      used as a co-monomer to produce hydrogels and fire-retardant materials. In this
      study, we engineered nonphosphorylative metabolism to produce mesaconate from d
      xylose and l-arabinose. This nonphosphorylative metabolism is orthogonal to the
      intrinsic pentose metabolism in Escherichia coli and has fewer enzymatic steps
      and a higher theoretical yield to TCA cycle intermediates than the pentose
      phosphate pathway. Here mesaconate production was enabled from the d-xylose
      pathway and the l-arabinose pathway. To enhance the transportation of d-xylose
      and l-arabinose, pentose transporters were examined. We identified the
      pentose/proton symporter, AraE, as the most effective transporter for both d
      xylose and l-arabinose in mesaconate production process. Further production
      optimization was achieved by operon screening and metabolic engineering. These
      efforts led to the engineered strains that produced 12.5g/l and 13.2g/l
      mesaconate after 48h from 20g/l of d-xylose and l-arabinose, respectively.
      Finally, the engineered strain overexpressing both l-arabinose and d-xylose
      operons produced 14.7g/l mesaconate from a 1:1 d-xylose and l-arabinose mixture
      with a yield of 85% of the theoretical maximum. (0.87g/g). This work demonstrates
      an effective system that converts pentoses into a value-added chemical,
      mesaconate, with promising titer, rate, and yield.

PMID- 27697563
TI  - Development of a Bacillus subtilis cell-free transcription-translation system for
      prototyping regulatory elements.
AB  - Cell-free transcription-translation systems were originally applied towards in
      vitro protein production. More recently, synthetic biology is enabling these
      systems to be used within a systematic design context for prototyping DNA
      regulatory elements, genetic logic circuits and biosynthetic pathways. The Gram
      positive soil bacterium, Bacillus subtilis, is an established model organism of
      industrial importance. To this end, we developed several B. subtilis-based cell
      free systems. Our improved B. subtilis WB800N-based system was capable of
      producing 0.8uM GFP, which gave a ~72x fold-improvement when compared with a B.
      subtilis 168 cell-free system. Our improved system was applied towards the
      prototyping of a B. subtilis promoter library in which we engineered several
      promoters, derived from the wild-type Pgrac (sigmaA) promoter, that display a
      range of comparable in vitro and in vivo transcriptional activities.
      Additionally, we demonstrate the cell-free characterisation of an inducible
      expression system, and the activity of a model enzyme - renilla luciferase.

PMID- 27697564
TI  - Continuous Home Care Reduces Hospice Disenrollment and Hospitalization After
      Hospice Enrollment.
AB  - CONTEXT: Among the four levels of hospice care, continuous home care (CHC) is the
      most expensive care, and infrequently provided in practice. OBJECTIVES: To
      identify hospice and patient characteristics associated with the use of CHC and
      to examine the associations between CHC utilization and hospice disenrollment or
      hospitalization after hospice enrollment. METHODS: Using 100% fee-for-service
      Medicare claims data for beneficiaries aged 66 years or older who died between
      July and December 2011, we identified the percentage of hospice agencies in which
      patients used CHC in 2011 and determined hospice and patient characteristics
      associated with the use of CHC. Using multivariable analyses, we examined the
      associations between CHC utilization and hospice disenrollment and
      hospitalization after hospice enrollment, adjusted for hospice and patient
      characteristics. RESULTS: Only 42.7% of hospices (1533 of 3592 hospices studied)
      provided CHC to at least one patient during the study period. Patients enrolled
      with for-profit, larger, and urban located hospices were more likely to use CHC
      (P < 0.001). Within these 1533 hospices, only 11.4% of patients used CHC.
      Patients who were white, had cancer, and had more comorbidities were more likely
      to use CHC. In multivariable models, compared with patients who did not use CHC,
      patients who used CHC were less likely to have hospice disenrollment (adjusted
      odds ratio 0.21; 95% CI 0.19, 0.23) and less likely to be hospitalized after
      hospice enrollment (adjusted odds ratio 0.37; 95% CI 0.34, 0.40). CONCLUSION:
      Although a minority of patients uses CHC, such services may be protective against
      hospice disenrollment and hospitalization after hospice enrollment.

PMID- 27697566
TI  - Hospice Value-Based Purchasing Program: A Model Design.
AB  - With the implementation of the Affordable Care Act, the U.S. government committed
      to a transition in payment policy for health care services linking reimbursement
      to improved health outcomes rather than the volume of services provided. To
      accomplish this goal, the Department of Health and Human Services is designing
      and implementing new payment models intended to improve the quality of health
      care while reducing its cost. Collectively, these novel payment models and
      programs have been characterized under the moniker of value-based purchasing
      (VBP), and although many of these models retain a fundamental fee-for-service
      (FFS) structure, they are seen as essential tools in the evolution away from
      volume-based health care financing toward a health system that provides "better
      care, smarter spending, and healthier people." In 2014, approximately 20% of
      Medicare provider FFS payments were linked to a VBP program. The Department of
      Health and Human Services has committed to a four-year plan to link 90% of
      Medicare provider FFS payments to value-based purchasing by 2018. To achieve this
      goal, all items and services currently reimbursed under Medicare FFS programs
      will need to be evaluated in the context of VBP. To this end, the Medicare
      Hospice benefit appears to be appropriate for inclusion in a model of VBP. This
      policy analysis proposes an adaptable model for a VBP program for the Medicare
      Hospice benefit linking payment to quality and efficiency in a manner consistent
      with statutory requirements established in the Affordable Care Act.

PMID- 27697565
TI  - Gender and Racial Differences in Stress, Coping, and Health-Related Quality of
      Life in Chronic Kidney Disease.
AB  - CONTEXT: Living with chronic kidney disease can be stressful and influence an
      individual's health-related quality of life. Effective coping strategies may
      reduce stress and improve quality of life in individuals with chronic medical
      conditions. OBJECTIVES: Health-related quality of life (HRQOL) is an important
      outcome for patients living with chronic kidney disease (CKD), and it is
      necessary to better understand potential gender and racial differences and
      predictors associated with reduced HRQOL, so that effective interventions can be
      developed. METHODS: Participants included 182 patients with CKD who were
      administered a battery of questions that included the Medical Outcomes Study
      Short-Form 36, Perceived Stress Scale, and the Brief COPE. Demographic and
      disease-specific information was abstracted from the patients' medical record.
      RESULTS: No differences by race were observed with regard to stress, quality of
      life, or coping with the exception that minority patients reported use of
      religious coping more often (P = 0.001) and had higher levels of energy compared
      with nonminority patients with CKD (P = 0.27). Women with CKD tended to use self
      distraction (P = 0.002), positive reframing (P = 0.035), venting (P = 0.024), and
      religious coping (P = 0 < 0.001) more often than men. No significant differences
      in perceived stress or domains of quality of life were observed between men and
      women with CKD. A link between coping strategies and HRQOL was observed in women
      (P = 0.001-0.02) but not men. Perceived stress was associated with poorer quality
      of life for men (P = 0.017 to <0.001) and women (P = 0.001 to <0.001), but more
      domains of men's quality of life were affected by perceived stress compared with
      women. CONCLUSIONS: The findings of the study suggest that the wider range of
      coping strategies used by women may be associated with buffering the link between
      perceived stress and quality of life. Men with CKD may benefit from interventions
      that not only reduce stress but also facilitate the use of a broader range of
      coping strategies to reduce stress and improve quality of life.

PMID- 27697568
TI  - Somatostatin Analogues Compared With Placebo and Other Pharmacologic Agents in
      the Management of Symptoms of Inoperable Malignant Bowel Obstruction: A
      Systematic Review.
AB  - CONTEXT: Somatostatin analogues are commonly used to relieve symptoms in
      malignant bowel obstruction (MBO) but are more expensive than other antisecretory
      agents. OBJECTIVES: To evaluate the evidence of effectiveness of somatostatin
      analogues compared with placebo and/or other pharmacologic agents in relieving
      vomiting in patients with inoperable MBO. METHODS: MEDLINE, EMBASE, CINAHL, and
      The Cochrane Controlled Trials Register databases were systematically searched;
      reference lists of relevant articles were hand searched. Cochrane risk of bias
      tool was used. RESULTS: The search identified 420 unique studies. Seven
      randomized controlled trials (RCTs) met the inclusion criteria (six octreotide
      studies and one lanreotide); 220 people administered somatostatin analogues and
      207 placebo or hyoscine butylbromide. Three RCTs compared a somatostatin analogue
      with placebo and four with hyoscine butylbromide. Two adequately powered
      multicenter RCTs with a low Cochrane risk of bias reported no significant
      difference between somatostatin analogues and placebo in their primary end
      points. Four RCTs with a high/unclear Cochrane risk of bias reported that
      somatostatin analogues were more effective than hyoscine butylbromide in reducing
      vomiting. CONCLUSION: There is low-level evidence of benefit with somatostatin
      analogues in the symptomatic treatment of MBO. However, high-level evidence from
      trials with low risk of bias found no benefit of somatostatin analogues for their
      primary outcome. There is debate regarding the clinically relevant study end
      point for symptom control in MBO and when it should be measured. The role of
      somatostatin analogues in this clinical situation requires further adequately
      powered, well-designed trials with agreed clinically important end points and
      measures.

PMID- 27697567
TI  - The Symptom Experience in Rectal Cancer Survivors.
AB  - CONTEXT: As the number of rectal cancer survivors grows, it is important to
      understand the symptom experience after treatment. Although data show that rectal
      cancer survivors experience a variety of symptoms after diagnosis, little has
      been done to study the way these symptoms are grouped and associated. OBJECTIVES:
      To determine symptom prevalence and intensity in rectal cancer survivors and if
      clusters of survivors exist, who share similar symptom-defined survivor subgroups
      that may vary based on antecedent variables. METHODS: A secondary analysis of the
      Cancer Care and Outcomes Research and Surveillance database was undertaken.
      Cluster analysis was performed on 15-month postdiagnosis data to form post
      treatment survivor subgroups, and these were examined for differences in
      demographic and clinical characteristics. Data were analyzed using cluster
      analysis, chi-square, and analysis of variance. RESULTS: A total of 275 rectal
      cancer survivors were included who had undergone chemotherapy, radiation therapy,
      and surgery. Most frequently reported symptoms included feeling "worn out" (87%),
      feeling "tired" (85%), and "trouble sleeping" (66%). Four symptom-defined
      survivor subgroups (minimally symptomatic n = 40, tired and trouble sleeping n =
      138, moderate symptoms n = 42, and highly symptomatic n = 55) were identified
      with symptom differences existing among each subgroup. Age and being
      married/partnered were the only two antecedents found to differ across subgroups.
      CONCLUSION: This study documents differences in the symptom experience after
      treatment. The identification of survivor subgroups allows researchers to further
      investigate tailored, supportive care strategies to minimize ongoing symptoms in
      those with the greatest symptom burden.

PMID- 27697569
TI  - Performance of Consultative Palliative Care Model in Achieving Quality Metrics in
      the ICU.
AB  - CONTEXT: Quality metrics for intensive care unit (ICU)-based palliative care have
      been proposed, but it is unknown how consultative palliative care can contribute
      to performance on these measures. OBJECTIVES: Assess adherence to proposed
      quality metrics of ICU-based palliative care by palliative care specialists.
      METHODS: Surrogates for 9/14 patient-level quality metrics were assessed in all
      patients who received an initial palliative care specialist consult while in an
      ICU from 10/26/2012 to 1/16/2015 in the Global Palliative Care Quality Alliance,
      a nationwide palliative care quality registry. RESULTS: Two hundred fifty-four
      patients received an initial palliative care consultation in an ICU setting. Mean
      (SD) age was 67.5 (17.3) years, 52% were female. The most common reasons for
      consultation were symptom management (33%) and end-of-life transition (24%).
      Adherence to ICU quality metrics for palliative care was variable: clinicians
      documented presence or absence of advance directives in 36% of encounters,
      assessed pain in 52.0%, dyspnea in 50.8%, spiritual support in 62%, and reported
      an intervention for pain in 100% of patients with documented moderate to severe
      intensity pain. CONCLUSION: Palliative care consultations in an ICU setting are
      characterized by variable adherence to candidate ICU palliative care quality
      metrics. Although symptom management was the most common reason for palliative
      care consultation, consultants infrequently documented symptom assessments.
      Palliative care consultants performed better in offering spiritual support and
      managing documented symptoms. These results highlight specific competencies of
      consultative palliative care that should be complimented by ICU teams to ensure
      high-quality comprehensive care for the critically ill.

PMID- 27697570
TI  - Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary
      disease.
AB  - Serum metabolic profiling can identify the metabolites responsible for
      discrimination between doxycycline treated and untreated chronic obstructive
      pulmonary disease (COPD) and explain the possible effect of doxycycline in
      improving the disease conditions. 1H nuclear magnetic resonance (NMR)-based
      metabolomics was used to obtain serum metabolic profiles of 60 add-on doxycycline
      treated COPD patients and 40 patients receiving standard therapy. The acquired
      data were analyzed using multivariate principal component analysis (PCA), partial
      least-squares-discriminant analysis (PLS-DA), and orthogonal projection to latent
      structure with discriminant analysis (OPLS-DA). A clear metabolic differentiation
      was apparent between the pre and post doxycycline treated group. The
      distinguishing metabolites lactate and fatty acids were significantly down
      regulated and formate, citrate, imidazole and l-arginine upregulated. Lactate and
      folate are further validated biochemically. Metabolic changes, such as decreased
      lactate level, inhibited arginase activity and lowered fatty acid level observed
      in COPD patients in response to add-on doxycycline treatment, reflect the anti
      inflammatory action of the drug. Doxycycline as a possible therapeutic option for
      COPD seems promising.

PMID- 27697571
TI  - Development and validation of a stability-indicating HPLC-UV method for the
      determination of Thiocolchicoside and its degradation products.
AB  - A stability indicating high performance liquid chromatography method has been
      developed for the determination of thiocolchicoside (TCC) and its main
      degradation products thiocolchicoside S-oxide (D1SO) and 3-O
      demethylthiocolchicine (D3) in liquid and solid formulations. The method was
      developed based on a previous forced degradation study showing that TCC underwent
      chemical degradation by acid/base catalyzed hydrolysis and oxidation being the
      main degradation products D3 and D1SO respectively. The analytes separation and
      quantification were achieved on a SynergiTM 4MUm Polar-RP 80A, column 150*4.6mm
      (Phenomenex) using the mobile phase constituted (flow rate 1mLmin-1) of eluant A:
      20mM sodium acetate buffer (pH 5.0) and eluant B: MeOH:CH3CN (20:80); the elution
      was performed in gradient mode detecting the analytes at 254nm. The method showed
      linearity for TCC assay in the 5-15MUgmL-1, range and for unknown (TCCfu) and
      known (D1SO and D3) degradation products assay, in the 0.5-10MUgmL-1 range: all
      the square of the correlation coefficients were greater than 0.999. The
      precision, determined in terms of intra-day and inter-day were expressed as RSDs
      and resulted to be 1.19, 1.10, 1.37 and 1.04% and 0.95, 0.83, 1.30 and 0.72 for
      TCC, TCCfu, D1SO and D3, respectively. The method demonstrated also to be
      accurate; indeed, the average recoveries were 102.1/102.0% for TCC (ampoules and
      hard capsules respectively), 101.3/100.3% for TCCfu, 101.7/100.2% for D1SO, and
      101.4/101.4% for D3. The robustness was also evaluated by variations of mobile
      phase composition and pH. Finally, the applicability of the method was evaluated
      by analysis of commercial liquid and solid dosage forms.

PMID- 27697572
TI  - Dried blood spot analysis of gabapentin as a valid alternative for serum: a
      bridging study.
AB  - We evaluated the applicability of a validated GC-MS method for the determination
      of gabapentin in dried blood spots (DBS). Important for the acceptance of DBS
      sampling as an alternative sampling strategy is the possibility to base solid
      conclusions on the quantification. Therefore, bridging studies -studies in which
      the correlation between both DBS and a reference matrix (e.g. serum) is evaluated
      statistically- need to be conducted. To this end, a comparative study was set up
      to quantify gabapentin in both blood (DBS) and serum samples. Statistically
      significant differences between DBS and serum concentrations were found
      (p<0.001). A mean blood-to-serum ratio of 0.85 was observed, which is in line
      with expectations. Calculated serum concentrations (obtained by dividing the DBS
      concentrations by 0.85) demonstrated a good correlation with measured serum
      concentrations, with 87% of samples fulfilling the criterion for incurred sample
      reanalysis. Furthermore, our data indicate a good correlation between capillary
      and venous concentrations. Conclusively, this study demonstrated that DBS are a
      valid alternative to serum for the determination of gabapentin.

PMID- 27697573
TI  - NMR-based metabonomics and correlation analysis reveal potential biomarkers
      associated with chronic atrophic gastritis.
AB  - Chronic atrophic gastritis (CAG) is one of the most important pre-cancerous
      states with a high prevalence. Exploring of the underlying mechanism and
      potential biomarkers is of significant importance for CAG. In the present work,
      1H NMR-based metabonomics with correlative analysis was performed to analyze the
      metabolic features of CAG. 19 plasma metabolites and 18 urine metabolites were
      enrolled to construct the circulatory and excretory metabolome of CAG, which was
      in response to alterations of energy metabolism, inflammation, immune
      dysfunction, as well as oxidative stress. 7 plasma biomarkers and 7 urine
      biomarkers were screened to elucidate the pathogenesis of CAG based on the
      further correlation analysis with biochemical indexes. Finally, 3 plasma
      biomarkers (arginine, succinate and 3-hydroxybutyrate) and 2 urine biomarkers
      (alpha-ketoglutarate and valine) highlighted the potential to indicate risks of
      CAG in virtue of correlation with pepsin activity and ROC analysis. Here, our
      results paved a way for elucidating the underlying mechanisms in the development
      of CAG, and provided new avenues for the diagnosis of CAG and presented potential
      drug targets for treatment of CAG.

PMID- 27697574
TI  - Combination of HPLC-MS and QAMS as a new analytical approach for determination of
      saponins in ginseng containing products.
AB  - Conventional liquid chromatographic methods coupled with ultraviolet detection
      with low-wavelength range are lacking selectivity and sensitivity to determine
      both polar and less polar ginsenosides. Also the lack of standard substances for
      such quality control methods is leading to development of the approaches using
      single standard for quantitative analysis of multi-component system (QAMS). The
      objective of present study was to establish and compare for the first time liquid
      chromatography-ultraviolet detection and liquid chromatography-mass spectrometry
      QAMS methods for the simultaneous determination of protopanaxatriol-type and
      protopanaxadiol-type ginsenosides in a variety of ginseng products. Sixteen polar
      and less polar ginsenosides were separated on a reversed-phase C18-column
      (150mm*2.0mm, 2.2MUm) with a mobile phase consisting of 0.1% formic acid in water
      and acetonitrile. Components were then detected by means of ultraviolet and mass
      spectrometry detection. Characteristic sapogenin fragmentation signals with m/z
      423 and 425 for two major groups of ginseng saponins allowed their simultaneous
      determination in a single chromatographic run, while the use of ultraviolet
      detection tends to give overvalued results. Structural correlation between the
      relative response factors and saponin structure was demonstrated. The method was
      linear (R2 >0.999) and sensitive (LODs, 0.01-0.03mg/mL) within the concentration
      range tested. Concentrations of individual ginsenosides and several quality
      control parameters were determined in ginseng root extracts and commercial
      ginseng products of different types (root slices, tablets and tea samples), and
      results showed that ginsenoside content can be successfully measured by means of
      QAMS approach.

PMID- 27697575
TI  - An integrated strategy for establishment of curcuminoid profile in turmeric using
      two LC-MS/MS platforms.
AB  - Turmeric and curcuminoids are used as natural food coloring and functional food
      additives in various parts of the world. In this study, ninety-six curcuminoids
      were fully characterized using a targeted curcuminoid profile, which established
      by integrated use of two complementary LC-MS/MS platforms (liquid chromatography
      quadrupole time of flight mass spectrometry (LC-QTOF-MS/MS) and liquid
      chromatography-quadrupole linear ion trap mass spectrometry (LC-QTRAP-MS/MS)).
      The curcuminoid profile was represented in the form of a multiple reaction
      monitoring (MRM) mode based on LC-QTRAP-MS/MS analysis. It facilitated the
      qualitative and relative quantitative analysis of curcuminoids in a single
      injection. Meanwhile, the profile was successfully applied to the quality
      evaluation of raw materials of turmeric from different regions in China and
      Myanmar. The structural identification procedures of curcuminoids and the
      integrated strategy provide a suitable method to analyze targeted plant
      metabolites which occur in a high number but sharing either structural
      similarities or similar functional groups.

PMID- 27697576
TI  - Testicular Torsion Presentation Trends before and after Pediatric Urology
      Subspecialty Certification.
AB  - PURPOSE: We examined testicular torsion presentation and referral trends at our
      institution before and after pediatric urology subspecialty certification.
      MATERIALS AND METHODS: We reviewed patients with testicular torsion presenting
      directly to our pediatric hospital emergency department ("direct") or transferred
      urgently from an outside institution ("referred") who underwent detorsion and
      orchiopexy or orchiectomy between 2005 and 2015. Presentations were considered
      acute (less than 24 hours) or delayed (24 hours or greater) based on time from
      symptom onset. Primary outcomes were case volume and presentation trends through
      time. Secondary outcomes were effect of presenting location and transport
      variables on orchiectomy rate. RESULTS: Incidence of testicular torsion increased
      from 15 cases in 2005 to 32 in 2015. Annual incidence of direct cases increased
      slightly during the study period from 12 to 17, whereas incidence of referred
      cases increased from 3 in 2005 to 15 in 2015. Proportion of referred acute cases
      markedly increased from precertification (4 of 63, 6.3%) to postcertification
      period (42 of 155, 27.1%; p <0.01). The majority of referred cases (59 of 83,
      71.1%) presented during weekday nights or weekends compared to a minority of
      direct cases (59 of 135, 43.7%; p <0.01). Orchiectomy rates were similar between
      direct and referred cases across all study periods and were not significantly
      impacted by presentation location, transport distance or transport modality (all
      p >0.05). CONCLUSIONS: Patients with testicular torsion have been increasingly
      referred to our institution, with the majority presenting on weekday nights and
      weekends. Our data do not support routinely transferring these patients to
      dedicated pediatric hospitals.

PMID- 27697577
TI  - Association of Sleep Disordered Breathing with Erectile Dysfunction in Community
      Dwelling Older Men.
AB  - PURPOSE: We investigated the association between sleep disordered breathing and
      erectile dysfunction in older men. MATERIALS AND METHODS: We performed a cross
      sectional analysis of community dwelling men age 67 years or older enrolled in
      the Osteoporotic Fractures in Men Sleep Study. Participants underwent overnight
      polysomnography (2003 to 2005) and completed sexual health questionnaires (2005
      to 2006). We defined sleep disordered breathing using the apnea-hypopnea index or
      nocturnal hypoxemia. Erectile dysfunction was defined using the MMAS
      (Massachusetts Male Aging Study) scale and, in sexually active men, the
      International Index of Erectile Function. We used logistic regression to examine
      the association between sleep disordered breathing and erectile dysfunction.
      RESULTS: Mean participant age was 76+/-5 years. Of the 2,676 men completing the
      MMAS, 70% had moderate to complete erectile dysfunction. Among 1,099 sexually
      active men completing the IIEF-5 (5-item International Index of Erectile
      Function), 26% had moderate to severe erectile dysfunction. A higher apnea
      hypopnea index was associated with greater odds of MMAS defined moderate to
      complete erectile dysfunction after adjusting for age and study site (OR 1.39,
      95% CI 1.00-1.92 for severe sleep disordered breathing vs none, p trend=0.008),
      but not after further adjustment for body mass index, socioeconomic status and
      comorbidities (OR 1.05, 95% CI 0.75-1.49, p trend=0.452). Greater nocturnal
      hypoxemia was associated with increased odds of MMAS defined moderate to complete
      erectile dysfunction (unadjusted OR 1.36, 95% Cl 1.04-1.80 vs none) but this was
      attenuated after adjustment for age and study site (OR 1.24, 95% CI 0.92-1.66).
      Sleep disordered breathing was not associated with erectile dysfunction by 5-item
      International Index of Erectile Function. CONCLUSIONS: In this cross-sectional
      analysis in older men sleep disordered breathing was associated with higher odds
      of erectile dysfunction in unadjusted analyses that was largely explained by
      higher body mass index and increased comorbidity among men with sleep disordered
      breathing. Prospective studies accounting for obesity and multimorbidity would
      further clarify the association of sleep disordered breathing and erectile
      dysfunction.

PMID- 27697579
TI  - Improving Organ Salvage in Testicular Torsion: Comparative Study of Patients
      Undergoing vs Not Undergoing Preoperative Manual Detorsion.
AB  - PURPOSE: We compared surgical outcomes between patients undergoing and those not
      undergoing preoperative manual detorsion for intravaginal testicular torsion.
      MATERIALS AND METHODS: We retrospectively analyzed consecutive patients treated
      surgically for testicular torsion who were examined within 24 hours of symptoms
      at our emergency department between January 2012 and September 2015. Explanatory
      variables were age, presentation delay (time between symptoms and urological
      examination), surgical wait time (time from examination to surgery), and whether
      manual detorsion was attempted and, if attempted, was declared successful. End
      points were surgical outcome (orchiopexy, orchiectomy) and testicular rotation at
      surgery. Statistical analysis included nonparametric tests and logistic
      regression. Statistical significance and confidence intervals were set at p <0.05
      and 0.95, respectively. RESULTS: Detorsion was attempted in 76 of 133 cases
      (57.1%) and was successful in 72 (95.1%). Patient age (median 15.6 vs 17.4 years,
      p = 0.115), presentation delay (6.6 vs 6.3 hours, p = 1.0) and surgical wait time
      (3.5 vs 3.2 hours, p = 0.412) were comparable between patients who underwent
      manual detorsion attempt and those who did not. Testicular rotation was less
      among successfully detorsed patients. Orchiectomy was performed in 2 of 72
      successfully detorsed patients (2.8%), compared to 15 of 61 patients (24.6%) in
      whom detorsion was not attempted or was unsuccessful (OR 11.23, p = 0.0002).
      Logistic regression indicated that surgical wait time (OR 0.95, p = 0.002) and
      successful detorsion (OR 17.38, p = 0.001) were independently associated with
      orchiopexy. CONCLUSIONS: Preoperative manual detorsion was associated with
      improved surgical salvage in patients with testicular torsion.

PMID- 27697578
TI  - Expression of Programmed Death Ligand 1 in Penile Cancer is of Prognostic Value
      and Associated with HPV Status.
AB  - PURPOSE: PD-L1 (programmed death ligand 1) inhibits T-cell function and prevents
      tumor eradication. This is facilitated by PD-L1 positive tumor cells and PD-L1
      positive immune cells, and can be prevented by anti-PD-1 (programmed death 1)/PD
      L1 immunotherapy. In advanced penile cancer there is a need for new therapeutic
      strategies. We investigated PD-L1 expression in penile cancers and compared PD-L1
      expression with disease specific survival, lymph node metastases at diagnosis and
      high risk HPV status in a large patient cohort. MATERIALS AND METHODS: A total of
      213 primary tumors were immunohistochemically stained for PD-L1 and scored for
      tumor (percentage), stroma (binary) and PD-L1 positive tumor infiltrating
      macrophages. Additionally, PD-L1 positive tumors were scored for expression
      pattern, that is diffuse or predominantly present at the tumor-stroma margin.
      RESULTS: Staining was successful in 200 tumors, of which 75% were high risk HPV
      negative. Median followup was 62 months. Of 200 tumors 96 (48%) were PD-L1
      positive (scored 1% or greater), of which 59 (62%) had a marginal expression
      pattern and 79 (82%) were high risk HPV negative (p = 0.03). Compared to PD-L1
      negative tumors, the PD-L1 expression patterns had different prognostic values in
      the whole cohort as well as in the high risk HPV negative subgroup. On
      multivariable analyses a marginal expression pattern was associated with absent
      lymph node metastases (OR 0.4) while diffuse expression was associated with poor
      survival (HR 2.58). These results were more prominent in the high risk HPV
      negative subgroup (OR 0.25, HR 3.92). CONCLUSIONS: PD-L1 was expressed in 48% of
      penile carcinomas and mainly in high risk HPV negative tumors. The pattern of
      expression was a prognostic factor as marginal expression was associated with
      absent lymph node metastases and diffuse expression was associated with poor
      survival.

PMID- 27697580
TI  - Nanoknife Electroporation Ablation Trial: A Prospective Development Study
      Investigating Focal Irreversible Electroporation for Localized Prostate Cancer.
AB  - PURPOSE: Irreversible electroporation has attractive attributes for focal
      ablation, namely nonthermal effect, precise demarcation of treatment and tissue
      selectivity. We report a prospective development study investigating focal
      irreversible electroporation. MATERIALS AND METHODS: A total of 20 men with
      certain characteristics were recruited for study, including a visible index
      lesion on anterior magnetic resonance imaging that was concordant with
      transperineal targeted and template prostate mapping biopsy, absent clinically
      significant disease noted elsewhere (University College London definition 2) and
      prostate specific antigen 15 ng/ml or less. Our primary objective was to
      determine the side effect profile at 12 months. Secondary objectives included the
      domain specific toxicity profile using patient reported outcomes and early
      disease control using magnetic resonance imaging targeted biopsy. RESULTS: A
      total of 19 patients with median age of 60 years (IQR 53-66) and median prostate
      specific antigen 7.75 ng/ml (IQR 5.5-10.03) were treated. Of the patients 16 were
      available for estimating the first outcome as 1 was lost to followup and 2 had
      received another form of treatment by study end. All 16 men had pad-free/leak
      free continence at 12 months. The proportion of men with erection sufficient for
      penetration decreased from 12 of 16 (75%) to 11 of 16 (69%). No serious adverse
      events were recorded. There was a statistically significant improvement in
      urinary symptoms according to changes in UCLA-EPIC (UCLA Expanded Prostate Cancer
      Index Composite) and I-PSS (International Prostate Symptom Score) (p = 0.039 and
      0.001, respectively). Erectile function remained stable according to the change
      in IIEF-15 (15-Item International Index of Erectile Function) (p = 0.572). Median
      prostate specific antigen significantly decreased to 1.71 ng/ml (p = 0.001). One
      man refused followup biopsy. No residual disease was found in 11 patients
      (61.1%). One man (5.6%) harbored clinically insignificant disease and the
      remaining 6 (33.3%) harbored clinically significant disease. CONCLUSIONS: Focal
      irreversible electroporation has low genitourinary toxicity. Additional studies
      are needed to optimize patient selection and treatment parameters.

PMID- 27697581
TI  - Phase I Results from a Study of Crizotinib in Combination with Erlotinib in
      Patients with Advanced Nonsquamous Non-Small Cell Lung Cancer.
AB  - INTRODUCTION: This phase I trial was conducted to determine the safety, maximum
      tolerated dose (MTD)/recommended phase II dose, and efficacy of crizotinib plus
      erlotinib in patients with advanced NSCLC. METHODS: Patients with NSCLC and an
      Eastern Cooperative Oncology Group performance status of 0 to 2 after failure of
      one or two prior chemotherapy regimens were eligible. Erlotinib, 100 mg, was
      given continuously once daily starting between day -14 and -7; crizotinib, 200 mg
      twice daily (dose level 1) or 150 mg twice daily (dose level -1), was added
      continuously beginning on day 1 of treatment cycle 1. Potential pharmacokinetic
      interactions between crizotinib and erlotinib were evaluated. RESULTS: Twenty
      seven patients received treatment; 26 received crizotinib plus erlotinib.
      Frequent adverse events were diarrhea, rash, decreased appetite, and fatigue.
      Dose-limiting toxicities were dehydration, diarrhea, dry eye, dysphagia,
      dyspepsia, esophagitis and vomiting. The MTD was crizotinib, 150 mg twice daily,
      with erlotinib, 100 mg once daily. Crizotinib increased the erlotinib area under
      the concentration-time curve 1.5-fold (dose level -1) and 1.8-fold (dose level
      1). The plasma level of crizotinib appeared to be unaffected by coadministration
      of erlotinib. Two patients whose tumors harbored activating EGFR mutations
      achieved confirmed partial responses, one at each crizotinib dose level.
      CONCLUSIONS: The MTD of the combination of crizotinib and erlotinib in patients
      with advanced NSCLC was crizotinib, 150 mg twice daily, with erlotinib, 100 mg
      once daily, which is less than the approved dose of either agent. The phase II
      portion of the study was not initiated.

PMID- 27697582
TI  - Risk of caries adjacent to different restoration materials: Systematic review of
      in situ studies.
AB  - OBJECTIVES: The risk of 'caries adjacent to restorations' (CAR) might depend on
      the used restorative materials. In situ studies are often used to compare the
      risk of caries adjacent to different materials. We aimed to review in situ
      studies to evaluate how different materials contribute to risk of CAR. DATA
      SOURCES: We included in situ controlled trials comparing directly placed
      restorative materials, reporting on caries (mineral loss, measured via
      radiography or micro-hardness) adjacent to these materials. Medline, Embase and
      Cochrane CENTRAL were systematically searched. Screening and data extraction was
      performed independently by two authors. Materials were classified according to
      the used adhesive and restorative materials. Fixed-effects pairwise and
      frequentistic network meta-analyses were performed STUDY SELECTION: Nine studies
      (132 patients, 8 materials) were included, yielding inconsistent results. We
      could not identify underlying reasons, as confounders were only limitedly
      reported. The resulting material rankings come with great uncertainty, and raise
      doubts as to the validity and transferability of in situ studies as well as the
      applicability of their findings. CONCLUSIONS: The current body of evidence of in
      situ studies is insufficient for firm conclusions as to the caries risk adjacent
      to different materials. The validity and applicability of included studies remain
      uncertain. CLINICAL SIGNIFICANCE: While single in situ studies seem to convey
      consistent and applicable information, the overall body of evidence is
      inconsistent, limiting the conclusions which can be drawn from it.

PMID- 27697583
TI  - Speech onset enhancement improves intelligibility in adverse listening conditions
      for cochlear implant users.
AB  - Speech perception by cochlear implant (CI) users can be very good in quiet but
      their speech intelligibility (SI) performance decreases in noisy environments.
      Because recent studies have shown that transient parts of the speech envelope are
      most important for SI in normal-hearing (NH) listeners, the enhanced envelope
      (EE) strategy was developed to emphasize onset cues of the speech envelope in the
      CI signal processing chain. The influence of enhancement of the onsets of the
      speech envelope on SI was investigated with CI users for speech in stationary
      speech-shaped noise (SSN) and with an interfering talker. All CI users showed an
      immediate benefit when a priori knowledge was used for the onset enhancement. A
      SI improvement was obtained at signal-to-noise ratios (SNRs) below 6 dB,
      corresponding to a speech reception threshold (SRT) improvement of 2.1 dB.
      Furthermore, stop consonant reception was improved with the EE strategy in quiet
      and in SSN at 6 dB SNR. For speech in speech, the SRT improvements were 2.1 dB
      and 1 dB when the onsets of the target speaker with a priori knowledge of the
      signal components or of the mixture of the target and the interfering speaker
      were enhanced, respectively. The latter demonstrates that a small benefit can be
      obtained without a priori knowledge.

PMID- 27697584
TI  - Perinatal exposure to bisphenol A modifies the transcriptional regulation of the
      beta-Casein gene during secretory activation of the rat mammary gland.
AB  - With the aim to analyze whether bisphenol A (BPA) modifies beta-Casein (beta-Cas)
      synthesis and transcriptional regulation in perinatally exposed animals, here,
      pregnant F0 rats were orally exposed to 0, 0.6 or 52 MUg BPA/kg/day from
      gestation day 9 until weaning. Then, F1 females were bred and mammary glands were
      obtained on lactation day 2. Perinatal BPA exposure decreased beta-Cas expression
      without modifying the activation of prolactin receptor. It also decreased the
      expression of glucocorticoid receptor in BPA52-exposed dams and beta1 and alpha6
      integrins as well as dystroglycan in both BPA groups. In addition, BPA exposure
      altered the expression of histone-modifying enzymes and induced histone
      modifications and DNA methylation in the promoter, enhancer and exon VII of the
      beta-Cas gene. An impaired crosstalk between the extracellular matrix and
      lactogenic hormone signaling pathways and epigenetic modifications of the beta
      Cas gene could be the molecular mechanisms by which BPA decreased beta-Cas
      expression.

PMID- 27697586
TI  - Precision medicine in diffuse large B-cell lymphoma: Hype or hope?

PMID- 27697585
TI  - Human Herpesvirus 6 Infection Following Haploidentical Transplantation: Immune
      Recovery and Outcome.
AB  - Human herpesvirus 6 (HHV-6) is increasingly recognized as a potentially life
      threatening pathogen in allogeneic hematopoietic stem cell transplantation
      (alloSCT). We retrospectively evaluated 54 adult patients who developed
      positivity to HHV-6 after alloSCT. The median time from alloSCT to HHV-6
      reactivation was 34 days. HHV-6 was present in plasma samples from 31 patients,
      in bone marrow (BM) of 9 patients, in bronchoalveolar lavage fluid and liver or
      gut biopsy specimens from 33 patients, and in cerebrospinal fluid of 7 patients.
      Twenty-nine patients developed acute graft-versus-host disease (GVHD), mainly
      grade III-IV, and 15 had concomitant cytomegalovirus reactivation. The median
      absolute CD3+ lymphocyte count was 207 cells/uL. We reported the following
      clinical manifestations: fever in 43 patients, skin rash in 22, hepatitis in 19,
      diarrhea in 24, encephalitis in 10, BM suppression in 18, and delayed engraftment
      in 11. Antiviral pharmacologic treatment was administered to 37 patients;
      nonetheless, the mortality rate was relatively high in this population (overall
      survival [OS] at 1 year, 38% +/- 7%). A better OS was significantly associated
      with a CD3+ cell count >=200/uL at the time of HHV-6 reactivation (P = .0002). OS
      was also positively affected by the absence of acute GVHD grade III-IV (P = .03)
      and by complete disease remission (P = .03), but was not significantly influenced
      by steroid administration, time after alloSCT, type of antiviral prophylaxis,
      plasma viral load, or organ involvement. Although HHV-6 detection typically
      occurred early after alloSCT, better T cell immune reconstitution seems to have
      the potential to improve clinical outcomes. Our findings provide new insight into
      the interplay between HHV-6 and the transplanted immune system.

PMID- 27697587
TI  - Reversal of schizophrenia-like symptoms and immune alterations in mice by
      immunomodulatory drugs.
AB  - Immune dysregulation observed in schizophrenia alters tryptophan metabolism.
      Tryptophan metabolism is triggered by indoleamine 2,3-dioxygenase (IDO) and
      tryptophan 2,3-dioxygenase (TDO). Tryptophan is converted to quinolinic acid, a
      potent neurotoxin, and to kynurenic acid, an NMDA antagonist. 1-Methyl-D
      tryptophan (MDT) inhibits IDO. Melatonin is metabolized by IDO while inhibiting
      TDO. We evaluated the reversal of ketamine-induced schizophrenia-like behavioral
      and neurochemical alterations in mice by the administration of MDT (20 or 40
      mg/kg, i.p.) or melatonin (15 mg/kg, per os). Oxidative stress and inflammatory
      alterations, i.e. myeloperoxidase activity (MPO), reduced glutathione (GSH),
      lipid peroxidation (LPO) and interleukin (IL)-4 and IL-6 were measured in the
      prefrontal cortex (PFC), hippocampus and striatum. Risperidone was used as
      standard antipsychotic. Ketamine triggered positive- (PPI deficits and
      hyperlocomotion), cognitive- (working memory deficits) and negative (social
      interaction deficits) schizophrenia-like symptoms. These symptoms were
      accompanied by increased MPO activity, decreased GSH and increased LPO in all
      brain areas and increments in hippocampal IL-4 and IL-6. MDT and melatonin
      reversed all ketamine-induced behavioral alterations. Risperidone did not reverse
      working memory deficits. MDT and melatonin reversed alterations in MPO activity
      and GSH levels. LP was reversed only by melatonin and risperidone. Risperidone
      could not reverse MPO alterations in the PFC and striatum. All drugs reversed the
      alterations in IL-4 and IL-6. The hippocampus and striatum of ketamine+melatonin
      treated animals had lower levels of IL-6. Our findings provide further
      preclinical evidence that immune-inflammatory and oxidative pathways are involved
      in schizophrenia and that targeting these pathways is a valid treatment option in
      schizophrenia.

PMID- 27697588
TI  - Metachronous anaplastic sarcoma of the kidney and thyroid follicular carcinoma as
      manifestations of DICER1 abnormalities.
AB  - Anaplastic sarcoma of the kidney (ASK) is a tumor found in the pediatric age
      group and shows many histopathological similarities to pleuropulmonary blastoma
      (PPB). We present a 12-year-old girl diagnosed with ASK and, 3 years later, with
      thyroid follicular carcinoma (TFC) with DICER1 abnormalities. Germline
      insertion/deletion (p. G1809_S1814delinsA) and independent somatic mutations (p.
      E1705K in ASK, p. E1813D in TFC) were identified. All of these abnormalities are
      in the catalytic domain of RNase IIIb. Single-nucleotide polymorphism genotyping
      microarray revealed independent copy number alterations (trisomy 8, monosomy 10,
      loss of 17p, and partial gain of 17q in ASK; trisomy 5 and partial loss of Xq in
      TFC). The copy number alteration pattern of ASK was similar to the pattern
      previously reported in PPB. The present case implies that ASK is a renal
      counterpart of PPB and that ASK with DICER1 abnormalities should be suspected in
      a broader age group than PPB.

PMID- 27697590
TI  - A prediction model for spontaneous regression of cervical intraepithelial
      neoplasia grade 2, based on simple clinical parameters.
AB  - This study aims to develop a prediction model for spontaneous regression of
      cervical intraepithelial neoplasia grade 2 (CIN 2) lesions based on simple
      clinicopathological parameters. The study was conducted at Maastricht University
      Medical Center, the Netherlands. The prediction model was developed in a
      retrospective cohort of 129 women with a histologic diagnosis of CIN 2 who were
      managed by watchful waiting for 6 to 24months. Five potential predictors for
      spontaneous regression were selected based on the literature and expert opinion
      and were analyzed in a multivariable logistic regression model, followed by
      backward stepwise deletion based on the Wald test. The prediction model was
      internally validated by the bootstrapping method. Discriminative capacity and
      accuracy were tested by assessing the area under the receiver operating
      characteristic curve (AUC) and a calibration plot. Disease regression within
      24months was seen in 91 (71%) of 129 patients. A prediction model was developed
      including the following variables: smoking, Papanicolaou test outcome before the
      CIN 2 diagnosis, concomitant CIN 1 diagnosis in the same biopsy, and more than 1
      biopsy containing CIN 2. Not smoking, Papanicolaou class <3, concomitant CIN 1,
      and no more than 1 biopsy containing CIN 2 were predictive of disease regression.
      The AUC was 69.2% (95% confidence interval, 58.5%-79.9%), indicating a moderate
      discriminative ability of the model. The calibration plot indicated good
      calibration of the predicted probabilities. This prediction model for spontaneous
      regression of CIN 2 may aid physicians in the personalized management of these
      lesions.

PMID- 27697589
TI  - Increased plasmacytic differentiation in gastric mucosa-associated lymphoid
      tissue lymphomas: Helicobacter pylori eradication response and IgG4+ plasma cell
      association.
AB  - Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare extranodal
      marginal zone B-cell lymphoma that is often associated with plasmacytic
      differentiation. However, the clinicopathological characteristics of gastric MALT
      lymphoma with increased plasmacytic differentiation have not yet been studied. To
      assess the clinicopathological implications of gastric MALT lymphoma with
      increased plasmacytic differentiation, 36 cases with increased plasmacytic
      differentiation and a control group of 16 cases with minimal plasmacytic
      differentiation were retrospectively collected from 65 primary gastric MALT
      lymphomas (2010-2012). The hematoxylin and eosin slides were reviewed, and IgG,
      IgG4, and kappa and lambda immunohistochemical staining was performed.
      Clinicopathological differences between the 2 groups were compared using the chi2
      test and odds ratios. Logistic regression analyses were used to evaluate
      resistance to Helicobacter pylori eradication therapy. Increased plasmacytic
      differentiation is significantly correlated with the H pylori eradication
      response (94.4% versus 66.7%, P=.018), lower frequency of relapse (5.6% versus
      35.7%, P=.014), the presence of more than one IgG4+ cell per high-power field
      (27.8% versus 0%, P=.022), and light-chain restriction (33.3% versus 6.2%,
      P=.044). Univariable logistic regression indicated that negative H pylori status
      (P=.016) and minimal plasmacytic differentiation (P=.019) were statistically
      significant predictive factors for resistance to H pylori eradication.
      Multivariable logistic regression analyses identified no statistically
      significant predictive factors. However, H pylori negativity and minimal
      plasmacytic differentiation showed a statistical trend toward significance
      (P=.078 and P=.09). Gastric MALT lymphomas with increased plasmacytic
      differentiation have different clinicopathological characteristics, and
      plasmacytic differentiation is associated with H pylori eradication response.

PMID- 27697591
TI  - Lipopolysaccharide and IL-1beta coordinate a synergy on cytokine production by
      upregulating MyD88 expression in human gingival fibroblasts.
AB  - Both lipopolysaccharide (LPS) and interleukin (IL)-1beta activate the MyD88
      dependent signaling pathways to stimulate proinflammatory cytokine expression.
      However, it remains unknown how LPS and IL-1beta interact with each other to
      coordinate the stimulation. In this study, we sought to investigate the
      interaction between LPS and IL-1beta on MyD88-dependent signaling pathways in
      human gingival fibroblasts (HGFs). Results showed that LPS derived from
      Porphyromonas gingivalis (Pg LPS) and IL-1beta cooperatively stimulated mitogen
      activated protein kinase (MAPK) and nuclear factor kappa B (NFkappaB) signaling
      pathways, and subsequent expression of proinflammatory cytokine expression.
      Furthermore, our results showed that Pg LPS and IL-1beta exerted a synergy on
      MyD88 expression and knockdown of MyD88 expression by small interfering RNA
      diminished the synergistic effect of Pg LPS and IL-1beta on IL-6 expression,
      suggesting that upregulation of MyD88 is involved in the coordinated stimulation
      by Pg LPS and IL-1beta of proinflammatory cytokine expression. Finally, our
      results showed that pharmacological inhibitors for MAPK and NFkappaB
      significantly reduced IL-6 secretion stimulated by Pg LPS and IL-1beta,
      indicating that the MyD88-dependent MAPK and NFkappaB signaling pathways are
      essential for the upregulation of proinflammatory cytokine expression by Pg LPS
      and IL-1beta. Taken together, this study showed that LPS and IL-1beta coordinate
      a synergy on cytokine production by upregulating MyD88 expression in HGFs.

PMID- 27697592
TI  - Suppressing Pitx2 inhibits proliferation and promotes differentiation of iHepSCs.
AB  - Induced hepatic stem cells (iHepSCs) have great potential as donors for liver
      cell therapy due to their abilities for self-renewal and bi-potential
      differentiation. However, the molecular mechanism regulating proliferation and
      differentiation of iHepSCs is poorly understood. In this study, we provide
      evidence that the homeodomain transcription factor, Pitx2, is essential to
      maintain iHepSCs stem cell characteristics. Suppressing Pitx2 expression in
      iHepSCs by lentivirus mediated specific shRNA markedly reduced the expression of
      the hepatic stem cell-associated genes (Lgr5, EpCAM, and Sox9) with concomitant
      inhibition of proliferation by blocking the G1/S phase transition, and these
      phenotypic changes were reversed upon re-expression of Pitx2. Pitx2 knockdown
      also resulted in up-regulation of the p53-induced Cdk inhibitor p21, and down
      regulation of its downstream effector CDK2-Cyclin E kinase complex. Furthermore,
      we observed that iHepSCs were more efficiently induced to differentiate into both
      hepatocytes and cholangiocytes when Pitx2 expression was suppressed, as compared
      to unmanipulated iHepSCs. These findings reveal that Pitx2 expression may be
      leveraged to control the status of iHepSCs during expansion in vitro to provide a
      strategy for further application of iHepSCs in liver cell therapy.

PMID- 27697593
TI  - What's the gist? The influence of schemas on the neural correlates underlying
      true and false memories.
AB  - The current study used a novel scene paradigm to investigate the role of encoding
      schemas on memory. Specifically, the study examined the influence of a strong
      encoding schema on retrieval of both schematic and non-schematic information, as
      well as false memories for information associated with the schema. Additionally,
      the separate roles of recollection and familiarity in both veridical and false
      memory retrieval were examined. The study identified several novel results.
      First, while many common neural regions mediated both schematic and non-schematic
      retrieval success, schematic recollection exhibited greater activation in visual
      cortex and hippocampus, regions commonly shown to mediate detailed retrieval.
      More effortful cognitive control regions in the prefrontal and parietal cortices,
      on the other hand, supported non-schematic recollection, while lateral temporal
      cortices supported familiarity-based retrieval of non-schematic items. Second,
      both true and false recollection, as well as familiarity, were mediated by
      activity in left middle temporal gyrus, a region associated with semantic
      processing and retrieval of schematic gist. Moreover, activity in this region was
      greater for both false recollection and false familiarity, suggesting a greater
      reliance on lateral temporal cortices for retrieval of illusory memories,
      irrespective of memory strength. Consistent with previous false memory studies,
      visual cortex showed increased activity for true compared to false recollection,
      suggesting that visual cortices are critical for distinguishing between
      previously viewed targets and related lures at retrieval. Additionally, the
      absence of common visual activity between true and false retrieval suggests that,
      unlike previous studies utilizing visual stimuli, when false memories are
      predicated on schematic gist and not perceptual overlap, there is little reliance
      on visual processes during false memory retrieval. Finally, the medial temporal
      lobe exhibited an interesting dissociation, showing greater activity for true
      compared to false recollection, as well as for false compared to true
      familiarity. These results provided an indication as to how different types of
      items are retrieved when studied within a highly schematic context. Results both
      replicate and extend previous true and false memory findings, supporting the
      Fuzzy Trace Theory.

PMID- 27697594
TI  - Drug repurposing for glioblastoma based on molecular subtypes.
AB  - A recent multi-platform analysis by The Cancer Genome Atlas identified four
      distinct molecular subtypes for glioblastoma (GBM) and demonstrated that the
      subtypes correlate with clinical phenotypes and treatment responses. In this
      study, we developed a computational drug repurposing approach to predict GBM
      drugs based on the molecular subtypes. Our approach leverages the genomic
      signature for each GBM subtype, and integrates the human cancer genomics with
      mouse phenotype data to identify the opportunity of reusing the FDA-approved
      agents to treat specific GBM subtypes. Specifically, we first constructed the
      phenotype profile for each GBM subtype using their genomic signatures. For each
      approved drug, we also constructed a phenotype profile using the drug target
      genes. Then we developed an algorithm to match and prioritize drugs based on
      their phenotypic similarities to the GBM subtypes. Our approach is highly
      generalizable for other disorders if provided with a list of disorder-specific
      genes. We first evaluated the approach in predicting drugs for the whole GBM. For
      a combined set of approved, potential and off-label GBM drugs, we achieved a
      median rank of 9.3%, which is significantly higher (p<e-7) than 45.7% for a
      recent approach that also uses the mouse phenotype data. Then we applied the
      approach on GBM subtypes. Analysis result shows the variations of enriched
      pathways, associated phenotypes and prioritized drugs across different subtypes.
      We ranked the first-line chemotherapy for GBM in different positions for each
      subtypes, and the rank variation was consistent with the previous finding on
      different drug responses among subtypes. In summary, this study makes an effort
      towards translating the molecular stratification into better survival for GBM.

PMID- 27697595
TI  - Impact of feed counterion addition and cyclone type on aerodynamic behavior of
      alginic-atenolol microparticles produced by spray drying.
AB  - The inhalatory route has emerged as an interesting non-invasive alternative for
      drug delivery. This allows both pulmonary (local) and systemic treatments (via
      alveolar absorption). Further advantages in terms of stability, dose and patient
      preference have often lead researchers to focus on dry powder inhaler delivery
      systems. Atenolol is an antihypertensive drug with low oral bioavailability and
      gastrointestinal side effects. Because atenolol possesses adequate permeation
      across human epithelial membranes, it has been proposed as a good candidate for
      inhalatory administration. In a previous work, atenolol was combined with alginic
      acid (AA) and microparticles were developed using spray-drying (SD) technology.
      Different AA/atenolol ratios, total feed solid content and operative variables
      were previously explored. In order to improve particle quality for inhalatory
      administration and the SD yield, in this work the AA acid groups not neutralized
      by atenolol were kept either free or neutralized to pH~7 and two different SD
      cyclones were used. Particle morphology, flow properties, moisture uptake and in
      vitro aerosolization behavior at different pressure drops were studied. When the
      AA acid groups were neutralized, particle size decreased as a consequence of the
      lower feed viscosity. The SD yield and in vitro particle deposition significantly
      increased when a high performance cyclone was employed, and even when lactose
      carrier particles were not used. Although the in vitro particle deposition
      decreased when the storage relative humidity increased, the developed SD powders
      showed adequate characteristics to be administered by inhalatory route up to
      storage relative humidities of about 60%.

PMID- 27697596
TI  - Efficient algorithm for discrimination of overlapping ultrasonic echoes.
AB  - We propose a method to identify the different echoes of an overlapped ultrasonic
      signal. This method is based on an iterative algorithm that compares the
      experimental signal to a realistic dictionary of trial functions and allows
      identification of one overlapped echo at each iteration. Adding physical
      parameters to the dictionary such as sample attenuation and ultrasound beam
      diffraction allows the method to be applied to various materials and sample
      geometries. Measurements at 500kHz and 5MHz on a ABS material and a copper plate
      are reported. The effectiveness and the robustness of the method are studied as a
      function of time delay between the different echoes. We show that taking into
      account the experimental set-up and material properties in the development of the
      dictionary are critical to identifying a round-trip signal when overlapping
      occurs.

PMID- 27697597
TI  - Exposure to Barbie: Effects on thin-ideal internalisation, body esteem, and body
      dissatisfaction among young girls.
AB  - Barbie doll ownership is high among girls in early primary school. It has been
      suggested that exposure to Barbie impacts negatively on body image. The present
      study sought to investigate the effect of exposure to Barbie on young girls' thin
      ideal internalisation, body esteem, and body dissatisfaction. Participants were
      160 girls (aged 5-8 years) from Adelaide, South Australia. They were randomly
      allocated one of three Barbie conditions (physical engagement, physical
      observation, print observation) or to a control toy. Results indicated that
      exposure to Barbie, irrespective of format, led to higher thin-ideal
      internalisation than exposure to the control, but had no impact on body esteem or
      body dissatisfaction. This suggests that interacting with Barbie may encourage
      girls in early primary school to adopt a preference for a thin body, but with no
      immediate effect on body image. The long-term impact of Barbie exposure on body
      image remains unknown.

PMID- 27697598
TI  - You know what? I'm happy. Cognitive bias is not related to personality but is
      induced by pair-housing in canaries (Serinus canaria).
AB  - Recent studies suggest that cognitive bias could constitute a novel and valid
      measure of animal welfare. Although interest for a link between personality and
      cognition is growing, no study to date investigated whether a cognitive bias
      might be related to the personality of the individuals. We trained 43 domestic
      canaries (Serinus canaria) to discriminate between two sides of a test cage, each
      side being associated with a different value (attractive or aversive food in a
      dish). During the test phase, the dish was placed at intermediate locations,
      representing ambiguous information. Results show evidence of an "optimistic" bias
      (flying faster to the dish at the ambiguous location) in birds housed in pairs,
      compared to birds housed singly, suggesting an influence of social context
      (living conditions) on canaries' emotions when tested individually. We also
      studied six traits of individuals' personality and found that aggressiveness,
      neophobia, one sociability index and obstinacy were repeatable across social
      context and/or day-light schedule, whereas the other sociability index, boldness
      and locomotion were not. No correlation between the birds' optimism and any of
      their personality traits was found, suggesting that cognitive bias may be a
      matter of social context rather than of individual personality.

PMID- 27697599
TI  - Chornobyl 30 years later: Radiation, pregnancies, and developmental anomalies in
      Rivne, Ukraine.
AB  - In the 30 years since the Chornobyl nuclear power plant disaster, there is
      evidence of persistent levels of incorporated ionizing radiation in adults,
      children and pregnant women in the surrounding area. Measured levels of Cesium
      137 vary by region, and may be influenced by dietary and water sources as well as
      proximity to nuclear power plants. Since 2000, comprehensive, population-based
      birth defects monitoring has been performed in selected regions of Ukraine to
      evaluate trends and to generate hypotheses regarding potential causes of
      unexplained variations in defect rates. Significantly higher rates of
      microcephaly, neural tube defects, and microphthalmia have been identified in
      selected regions of Ukraine collectively known as Polissia compared to adjacent
      regions collectively termed non-Polissia, and these significantly higher rates
      were evident particularly in the years 2000-2009. The Polissia regions have also
      demonstrated higher mean whole body counts of Cesium-137 compared to values in
      individuals residing in other non-Polissia regions. The potential causal
      relationship between persistent ionizing radiation pollution and selected
      congenital anomaly rates supports the need for a more thorough, targeted
      investigation of the sources of persistent ionizing radiation and the biological
      plausibility of a potential teratogenic effect.

PMID- 27697600
TI  - Racial and ethnic differences in associations between psychological distress and
      the presence of binge drinking: Results from the California health interview
      survey.
AB  - INTRODUCTION: Racial and ethnic minorities often suffer from poorer health than
      Whites given their exposure to more stressors and fewer resources that buffer the
      effects of stress. Given that alcohol is often consumed to alleviate the negative
      moods, the present study hypothesized that psychological distress may impact the
      involvement in binge drinking differently across racial and ethnic groups.
      METHODS: We used data from the California Health Interview Survey (CHIS) from
      2007 to 2012. The sample consisted of 130,556 adults including African Americans
      (N=6541), Asians (N=13,508), Latinos (N=18,128), and Whites (N=92,379). Binary
      logistic regression analysis was used with consideration for complex survey
      design. RESULTS: The results indicated that psychological distress was
      significantly associated with binge drinking across all racial and ethnic groups.
      However, this association differed by race and ethnicity adjusting for age,
      gender, marital status, education, poverty, and employment status. The results
      revealed that psychological distress had the largest effect on binge drinking for
      Asian Americans, particularly Filipinos and South Asians, compared to Whites.
      CONCLUSIONS: This study highlights the importance of examining racial and ethnic
      differences in the impacts of psychological distress on alcohol consumption.
      Future research is needed to better understand the potential factors that mediate
      the effects of psychological distress on binge drinking specific to each racial
      and ethnic group in order to develop culturally sensitive interventions and hence
      decrease the alcohol-related racial health disparities.

PMID- 27697603
TI  - Metabolism and chromatin dynamics in health and disease.
AB  - The regulation of gene expression in response to environmental and behavioural
      cues is critical for many biological processes. Histone tail modifications are
      dynamic and, as such, can regulate gene expression in response to extracellular
      conditions. Many of the enzymes involved in adding and removing these
      modifications require cofactors that are products of intermediary metabolism
      pathways, thus linking cellular metabolism to the regulation of gene expression.
      Furthermore, the expression and activity of such enzymes are influenced by the
      cellular concentrations of metabolic products. Under- and over-nutrition can
      induce epigenetic changes that influence chromatin structure and define a
      metabolic program. Importantly, recent studies have demonstrated that such
      changes during the pre- and peri-natal periods can be long-lasting, influencing
      the disease risk later in life and could be transmitted to subsequent
      generations. Moreover, damaging gene expression patterns observed in metabolic
      diseases such as diabetes are driven by persistent changes in chromatin
      structure, raising the possibility of targeting epigenetic pathways for the
      treatment of disease.

PMID- 27697602
TI  - Sensory processing sensitivity and serotonin gene variance: Insights into
      mechanisms shaping environmental sensitivity.
AB  - Current research supports the notion that the apparently innate trait Sensory
      Processing Sensitivity (SPS) may act as a modulator of development as function of
      the environment. Interestingly, the common serotonin transporter linked
      polymorphic region (5-HTTLPR) does the same. While neural mechanisms underlying
      SPS are largely unknown, those associated with the 5-HTTLPR have been extensively
      investigated. We perform a comparative analysis of research findings on sensory
      processing facets associated with the trait and polymorphism to: 1. detect shared
      phenotypes and frame a hypothesis towards neural mechanisms underlying SPS; 2.
      increase the understanding of 5-HTTLPR-associated behavioral patterns. Trait and
      polymorphism are both associated with differential susceptibility to
      environmental stimuli; additionally, both involve 1. having stronger emotional
      reactions, 2. processing of sensory information more deeply, 3. being more aware
      of environmental subtleties, and 4. being easily overstimulated. We discuss
      neural mechanisms and environmental conditions that may underlie these four
      facets. Besides urging the actual assessment of the link between the two, the
      conclusions of our analyses may guide and focus future research strategies.

PMID- 27697601
TI  - Overcoming cisplatin resistance in non-small cell lung cancer with Mad2 silencing
      siRNA delivered systemically using EGFR-targeted chitosan nanoparticles.
AB  - : Efficiency of chemotherapy is often limited by low therapeutic index of the
      drug as well as emergence of inherent and acquired drug resistance in cancer
      cells. As a common strategy to overcome drug resistance, higher doses of chemo
      agents are administered. However, adverse side effects are usually increased as a
      consequence. A potentially effective approach is to combine chemotherapy with
      other therapeutic strategies such as small interfering RNAs (siRNAs) that allow
      the use of lower yet efficient doses of the anticancer drugs. We previously
      developed epidermal growth factor receptor (EGFR)-targeted chitosan (CS)
      nanoparticles as a versatile delivery system for silencing the essential mitotic
      checkpoint gene Mad2, and induce cell death. Here, we tested this system as a
      single therapy and in combination with cisplatin in cisplatin sensitive and
      resistant lung cancer models, and characterized its in vivo efficacy and safety.
      Combination treatment resulted in significant improvement in tumor inhibition
      that was strikingly more effective in cisplatin-resistant tumors. Importantly,
      effective cisplatin dosage was dramatically reduced in the co-therapy regimen
      resulting in negligible toxic effects from the drug as confirmed by parameters
      such as body weight gain, biochemical markers of hepatic and renal function, and
      histopathology of liver/kidney/spleen tissues. Overall, we demonstrate that the
      combination of Mad2 siRNA-loaded CS nanoparticles strategy with chemotherapeutic
      agents such as cisplatin constitutes an efficient and safe approach for the
      treatment of drug resistant tumors. STATEMENT OF SIGNIFICANCE: Lung cancer
      remains one of the leading killers in the United States and around the world.
      Platinum agents, including cisplatin, are the first line treatment in lung
      cancer, including non-small cell lung cancer (NSCLC), which is the predominant
      form of lung cancer. In this study, we have evaluated Mad2 cell-cycle checkpoint
      gene silencing using small interfering RNA (siRNA) delivered systemically using
      epidermal growth factor receptor-targeted chitosan nanoparticles in drug
      sensitive and resistant models of NSCLC. Our results show that Mad2 gene
      silencing using targeted chitosan nanoparticles has tremendous potential in
      overcoming platinum resistance in NSCLC.

PMID- 27697604
TI  - Fetal safety profile of aromatase inhibitors: Animal data.
AB  - Aromatase inhibitors (AIs) are a class of drugs that act by blocking the
      production of estrogens from androgens. The current review concentrates on the
      prenatal developmental toxicity of AIs in experimental models. Available data
      indicate that AIs may affect pregnancy at human therapeutic or lower doses. The
      window of vulnerability to AIs is not limited to organogenesis, but also includes
      the preimplantation stage and fetal periods. Decreased embryo/fetal survival was
      the prominent treatment-related effect. Morphological anomalies noted in fetuses
      exposed to AIs included skeletal anomalies, abnormal head morphology, increased
      ano-genital distance in female fetuses, and minor urinary tract system anomalies.
      Placental enlargement was consistently reported in rats and non-human primates
      after maternal treatment with several AIs. In conclusion, data from basic
      scientific research suggest that low intensity exposure to AIs applied during a
      wide gestational window can profoundly affect prenatal development.

PMID- 27697605
TI  - Design and implementation of the AIRWAYS-2 trial: A multi-centre cluster
      randomised controlled trial of the clinical and cost effectiveness of the i-gel
      supraglottic airway device versus tracheal intubation in the initial airway
      management of out of hospital cardiac arrest.
AB  - Health outcomes after out of hospital cardiac arrest (OHCA) are extremely poor,
      with only 7-9% of patients in the United Kingdom (UK) surviving to hospital
      discharge. Currently emergency medical services (EMS) use either tracheal
      intubation or newer supraglottic airway devices (SGAs) to provide advanced airway
      management during OHCA. Equipoise between the two techniques has led to calls for
      a well-designed randomised controlled trial. The primary objective of the AIRWAYS
      2 trial is to assess whether the clinical effectiveness of the i-gel, a second
      generation SGA, is superior to tracheal intubation in the initial airway
      management of OHCA patients in the UK. Paramedics recruited to the AIRWAYS-2
      trial are randomised to use either tracheal intubation or i-gel as their first
      advanced airway intervention. Adults who have had a non-traumatic OHCA and are
      attended by an AIRWAYS-2 paramedic are retrospectively assessed against
      eligibility criteria for inclusion. The primary outcome is the modified Rankin
      Scale score at hospital discharge. Secondary objectives are to: (i) estimate
      differences between groups in outcome measures relating to airway management,
      hospital stay and recovery at 3 and 6 months; (ii) estimate the cost
      effectiveness of the i-gel compared to tracheal intubation. Because OHCA patient
      needs immediate treatment there are several unusual features and challenges to
      the design and implementation of this trial; these include level of
      randomisation, the automatic enrolment model, enrolment of patients that lack
      capacity and minimisation of bias. Patient enrolment began in June 2015. The
      trial will enrol 9070 patients over two years. The results are expected to
      influence future resuscitation guidelines. Trial Registration ISRCTN: 08256118.

PMID- 27697606
TI  - A systematic review and meta-analysis of the association between arterial carbon
      dioxide tension and outcomes after cardiac arrest.
AB  - INTRODUCTION: Arterial carbon dioxide tension (PaCO2) abnormalities are common
      after cardiac arrest (CA). Maintaining a normal PaCO2 makes physiological sense
      and is recommended as a therapeutic target after CA, but few studies have
      examined the association between PaCO2 and patient outcomes. This systematic
      review and meta-analysis aimed to assess the effect of a low or high PaCO2 on
      patient outcomes after CA. METHODS: We searched MEDLINE, EMBASE, CINAHL and
      Cochrane CENTRAL, for studies that evaluated the association between PaCO2 and
      outcomes after CA. The primary outcome was hospital survival. Secondary outcomes
      included neurological status at the end of each study's follow up period,
      hospital discharge destination and 30-day survival. Meta-analysis was conducted
      if statistical heterogeneity was low. RESULTS: The systematic review included
      nine studies; eight provided sufficient quantitative data for meta-analysis.
      Using PaCO2 cut-points of <35mmHg and >45mmHg to define hypo- and hypercarbia,
      normocarbia was associated with increased hospital survival (odds ratio [OR]
      1.30, 95% confidence interval [CI] 1.23, 1.38). Normocarbia was also associated
      with a good neurological outcome (cerebral performance category score 1 or 2)
      compared to hypercarbia (OR 1.69, 95% CI 1.13, 2.51) when the analysis also
      included an additional study with a slightly different definition for normocarbia
      (PaCO2 30-50mmHg). CONCLUSIONS: From the limited data it appears PaCO2 has an
      important U-shape association with survival and outcomes after CA, consistent
      with international resuscitation guidelines' recommendation that normocarbia be
      targeted during post-resuscitation care.

PMID- 27697607
TI  - Enhanced removal of lead from contaminated soil by polyol-based deep eutectic
      solvents and saponin.
AB  - Deep eutectic solvents (DESs) are a class of green solvents analogous to ionic
      liquids, but less costly and easier to prepare. The objective of this study is to
      remove lead (Pb) from a contaminated soil by using polyol based DESs mixed with a
      natural surfactant saponin for the first time. The DESs used in this study were
      prepared by mixing a quaternary ammonium salt choline chloride with polyols e.g.
      glycerol and ethylene glycol. A natural surfactant saponin obtained from soapnut
      fruit pericarp, was mixed with DESs to boost their efficiency. The DESs on their
      own did not perform satisfactory due to higher pH; however, they improved the
      performance of soapnut by up to 100%. Pb removal from contaminated soil using
      mixture of 40% DES-Gly and 1% saponin and mixture of 10% DES-Gly and 2% saponin
      were above 72% XRD and SEM studies did not detect any major corrosion in the soil
      texture. The environmental friendliness of both DESs and saponin and their
      affordable costs merit thorough investigation of their potential as soil washing
      agents.

PMID- 27697608
TI  - Insight into the role of TSLP in inflammatory bowel diseases.
AB  - Proinflammatory cytokines are thought to modulate pathogeneses of various
      inflammatory bowel diseases (IBDs). Thymic stromal lymphopoietin (TSLP), which
      has been studied in various allergic diseases such as asthma, atopic dermatitis
      (AD) and eosinophilic esophagitis (EoE), has been less considered to be involved
      in IBDs. However, mucosal dendritic cells (DCs) induced by various cytokines
      including TSLP were reported to cause polarization of T cell toward Th2 response,
      the differentiation of regulatory T-cell (Treg), and secretion of IgA by B cells.
      In this review, we discuss the concept that decreased TSLP has the potential to
      accelerate the development of Th1 response dominant diseases such as the Crohn's
      disease (CD) while increased TSLP has the potential to lead to a development of
      Th2 cell dominant diseases such the ulcerative colitis (UC). To examine TSLP's
      role as a potential determining factor for differentiating UC and CD, we analyzed
      the effects of other genes regulated by TSLP in regards to the UC and CD
      pathogeneses using data from online open access resources such as NetPath,
      GeneMania, and the String database. Our findings indicate that TSLP is a key
      mediator in the pathogenesis of IBDs and that further studies are needed to
      evaluate its role.

PMID- 27697609
TI  - Characterization of genetic sequence variation of 58 STR loci in four major
      population groups.
AB  - Massively parallel sequencing (MPS) can identify sequence variation within short
      tandem repeat (STR) alleles as well as their nominal allele lengths that
      traditionally have been obtained by capillary electrophoresis. Using the MiSeq
      FGx Forensic Genomics System (Illumina), STRait Razor, and in-house excel
      workbooks, genetic variation was characterized within STR repeat and flanking
      regions of 27 autosomal, 7 X-chromosome and 24 Y-chromosome STR markers in 777
      unrelated individuals from four population groups. Seven hundred and forty six
      autosomal, 227 X-chromosome, and 324 Y-chromosome STR alleles were identified by
      sequence compared with 357 autosomal, 107 X-chromosome, and 189 Y-chromosome STR
      alleles that were identified by length. Within the observed sequence variation,
      227 autosomal, 156 X-chromosome, and 112 Y-chromosome novel alleles were
      identified and described. One hundred and seventy six autosomal, 123 X
      chromosome, and 93 Y-chromosome sequence variants resided within STR repeat
      regions, and 86 autosomal, 39 X-chromosome, and 20 Y-chromosome variants were
      located in STR flanking regions. Three markers, D18S51, DXS10135, and DYS385a-b
      had 1, 4, and 1 alleles, respectively, which contained both a novel repeat region
      variant and a flanking sequence variant in the same nucleotide sequence. There
      were 50 markers that demonstrated a relative increase in diversity with the
      variant sequence alleles compared with those of traditional nominal length
      alleles. These population data illustrate the genetic variation that exists in
      the commonly used STR markers in the selected population samples and provide
      allele frequencies for statistical calculations related to STR profiling with MPS
      data.

PMID- 27697610
TI  - Repression of Mcl-1 and disruption of the Mcl-1/Bak interaction in myeloma cells
      couple ER stress to mitochondrial apoptosis.
AB  - As myeloma cells actively produce and secrete immunoglobulins, they are prone to
      ER stress, which if unresolved leads to apoptosis. We found that myeloma cell
      death induced by the ER stressor Thapsigargin was highly variable, ranging from 2
      to 89%. Induction of ATF4 and CHOP was observed in myeloma cells under
      Thapsigargin independently of cell death. The decrease in Mcl-1 was associated
      with protein translation inhibition and identified as a crucial factor in
      Thapsigargin sensitivity, since it was the only Bcl-2 family protein
      differentially modified between sensitive and resistant myeloma cells. Bak but
      not Bax was found to contribute to Thapsigargin-induced apoptosis. Appropriately,
      a basal Mcl-1/Bak interaction was demonstrated in Thapsigargin-sensitive cells.
      Of note, the only pro-apoptotic protein freed from Mcl-1 under Thapsigargin was
      Bak, whereas Mcl-1/Noxa or Mcl-1/Bim complexes were simultaneously increased.
      Thus, the disruption of the basal Mcl-1/Bak complex in Thapsigargin-sensitive
      cells seemed to be an essential event in cell death induction, probably favored
      by the induced Noxa and Bim BH3-only proteins. These findings underscore the
      implication of the Mcl-1/Bak axis in myeloma cell death triggered by
      Thapsigargin.

PMID- 27697611
TI  - SEI1 induces genomic instability by inhibiting DNA damage response in ovarian
      cancer.
AB  - Previous studies have shown that the oncogene SEI1 is highly expressed in ovarian
      carcinomas, and promoting genomic instability. However, the molecular mechanism
      of SEI1 in promoting genomic instability remains unclear. We observed SEI1
      overexpression in 30 of 46 cases of ovarian cancer compared to non-tumor tissues
      and the overexpression of SEI1 was positively associated with the tumor FIGO
      stage. Our functional studies revealed that overexpression of SEI1 could induce
      genomic instability and increased DNA strand breaks. In contrast, SEI1 co
      localized with gammaH2AX and phosphorylated ATM and DNAPKcs in the nucleus.
      Furthermore, we found that overexpression of SEI1 induced translocation of the
      SEI1 protein from the cytoplasm to the nucleus; ATM and DNAPKcs were associated
      with the cytoplasm-to-nucleus translocation of SEI1. To further prove the
      correlation between the DNA damage response (DDR) and SEI1, we knocked down SEI1
      expression in SEI1-transfected ovarian cancer cell lines. The expression of DDR
      proteins was significantly downregulated, and the number of micronuclei was
      significantly decreased. Together, these results define a new mechanism of SEI1
      in the regulation of genomic stability and in the malignant progression of
      ovarian cancer.

PMID- 27697612
TI  - Exploring sex differences in the adult zebra finch brain: In vivo diffusion
      tensor imaging and ex vivo super-resolution track density imaging.
AB  - Zebra finches are an excellent model to study the process of vocal learning, a
      complex socially-learned tool of communication that forms the basis of spoken
      human language. So far, structural investigation of the zebra finch brain has
      been performed ex vivo using invasive methods such as histology. These methods
      are highly specific, however, they strongly interfere with performing whole-brain
      analyses and exclude longitudinal studies aimed at establishing causal
      correlations between neuroplastic events and specific behavioral performances.
      Therefore, the aim of the current study was to implement an in vivo Diffusion
      Tensor Imaging (DTI) protocol sensitive enough to detect structural sex
      differences in the adult zebra finch brain. Voxel-wise comparison of male and
      female DTI parameter maps shows clear differences in several components of the
      song control system (i.e. Area X surroundings, the high vocal center (HVC) and
      the lateral magnocellular nucleus of the anterior nidopallium (LMAN)), which
      corroborate previous findings and are in line with the clear behavioral
      difference as only males sing. Furthermore, to obtain additional insights into
      the 3-dimensional organization of the zebra finch brain and clarify findings
      obtained by the in vivo study, ex vivo DTI data of the male and female brain were
      acquired as well, using a recently established super-resolution reconstruction
      (SRR) imaging strategy. Interestingly, the SRR-DTI approach led to a marked
      reduction in acquisition time without interfering with the (spatial and angular)
      resolution and SNR which enabled to acquire a data set characterized by a 78MUm
      isotropic resolution including 90 diffusion gradient directions within 44h of
      scanning time. Based on the reconstructed SRR-DTI maps, whole brain probabilistic
      Track Density Imaging (TDI) was performed for the purpose of super resolved track
      density imaging, further pushing the resolution up to 40MUm isotropic. The DTI
      and TDI maps realized atlas-quality anatomical maps that enable a clear
      delineation of most components of the song control and auditory systems. In
      conclusion, this study paves the way for longitudinal in vivo and high-resolution
      ex vivo experiments aimed at disentangling neuroplastic events that characterize
      the critical period for vocal learning in zebra finch ontogeny.

PMID- 27697613
TI  - Swelling of the nose and upper lip in a young patient from the Comoro islands.

PMID- 27697614
TI  - Women's experiences with giving birth before arrival.
AB  - OBJECTIVE: To explore women's experiences with giving birth before arrival.
      DESIGN: A qualitative interview study. SETTING: Individual semi structured
      interviews with women from Western Norway conducted in their homes in 2015.
      PARTICIPANTS: 10 women who experienced BBA-births in 2014, or the beginning of
      2015. Two primiparous and eight multiparous women participated in the study. KEY
      FINDINGS: Three themes were generated from the analysis. In the encounter with
      the healthcare services, the women described midwives as gatekeepers defining
      active labour. Giving birth before arrival was dramatic, but at some point fear
      of giving birth alone was replaced by feelings of coping, and in hindsight they
      felt empowered. The women described giving birth before arrival to be a special
      experience, but this was not always acknowledged by the midwives. CONCLUSION AND
      IMPLICATIONS FOR PRACTICE: The findings in this study question the cost-benefit
      of today's maternity care system pointing towards a more differentiated and
      decentralised care. To enhance patient safety adequate capacity of midwives in
      the maternity care is essential. Furthermore, good communication skills are key
      to improving practice and enhancing safety. Further research must be conducted.

PMID- 27697615
TI  - Integrative transcriptomic analysis of NAFLD animal model reveals dysregulated
      genes and pathways in metabolism.
AB  - Dysregulation of metabolism in hepatocytes leads to hepatic diseases such as
      hepatitis and non-alcoholic fatty liver disease (NAFLD). NAFLD represents a
      spectrum of liver diseases ranging from simple steatosis to nonalcoholic
      steatohepatitis (NASH). NASH is likely to progress to cirrhosis, liver failure
      and hepatocellular carcinoma, which lead to poor long-term prognosis. However,
      the exact mechanism of development of NAFLD is not well elucidated. In order to
      better understand the pathogenesis of NAFLD, we have performed an integrative
      analysis to livers from NAFLD rat models in a global view of the transcriptome.
      By systemic and integrative analyses, we have found that transport, angiogenesis
      and cell adhesion were upregulated in response to high fat diet feeding, which
      may cause a large amount of free fatty acid transport, hepatic fibrosis and
      hepatocytes injury. GO tree analysis has shown that angiogenesis was upregulated.
      GO term in response to high fat diet which may cause fibrosis. The pathway
      interaction network has indicated that upregulated "valine, leucine, and
      isoleucine metabolism" may decrease the serum concentration of branched-chain
      amino acid (BCAA). The enhanced degradation of BCAA in NAFLD animal models may
      lead to inhibition of the regeneration of hepatocytes, reducing the production of
      albumin, attenuating the inhibition of liver cancer and decreasing immunity.
      Overall, high fat diet upregulated a variety of metabolism which have converged
      at TCA cycle. High fatty has pushed the hepatic mitochondria to a "busy state".
      Comprehensively, genes participated in dysregulated biological process and
      metabolisms may be served as indicators for evaluation of NAFLD progression and
      therapeutic targets.

PMID- 27697616
TI  - Lipid metabolism in Rhodnius prolixus: Lessons from the genome.
AB  - The kissing bug Rhodnius prolixus is both an important vector of Chagas' disease
      and an interesting model for investigation into the field of physiology,
      including lipid metabolism. The publication of this insect genome will bring a
      huge amount of new molecular biology data to be used in future experiments.
      Although this work represents a promising scenario, a preliminary analysis of the
      sequence data is necessary to identify and annotate the genes involved in lipid
      metabolism. Here, we used bioinformatics tools and gene expression analysis to
      explore genes from different genes families and pathways, including genes for fat
      breakdown, as lipases and phospholipases, and enzymes from beta-oxidation, fatty
      acid metabolism, and acyl-CoA and glycerolipid synthesis. The R. prolixus genome
      encodes 31 putative lipase genes, including 21 neutral lipases and 5 acid
      lipases. The expression profiles of some of these genes were analyzed. We were
      able to identify nine phospholipase A2 genes. A variety of gene families that
      participate in fatty acid synthesis and modification were studied, including
      fatty acid synthase, elongase, desaturase and reductase. Concerning the synthesis
      of glycerolipids, we found a second isoform of glycerol-3-phosphate
      acyltransferase that was ubiquitously expressed throughout the organs. Finally,
      all genes involved in fatty acid beta-oxidation were identified, but not a long
      chain acyl-CoA dehydrogenase. These results provide fundamental data to be used
      in future research on insect lipid metabolism and its possible relevance to
      Chagas' disease transmission.

PMID- 27697617
TI  - Alcohol-associated cancer and deregulation of Pol III genes.
AB  - Emerging evidence indicates that alcohol intake is associated with human cancers
      in different organs. However, the molecular mechanism of alcohol-associated human
      cancers remains to be elucidated. Here, this paper aimed to clarify a novel
      mechanism of alcohol-promoted cell transformation and tumor development. Alcohol
      induces JNK1 activation and increases cellular levels of c-Jun to upregulate Brf1
      expression and Pol III gene transcription, leading to an enhancement of rates of
      cell transformation and tumor formation.

PMID- 27697618
TI  - Au-Ag core-shell nanoparticles for simultaneous bacterial imaging and synergistic
      antibacterial activity.
AB  - Au@Ag nanoparticles (NPs) were recently found to display giant two-photon
      photoluminescence (2PPL) enhancement, with an enhancement factor up to 815 fold
      upon aggregate formation. Based on this finding, two-photon imaging of bacteria
      by Au@Ag NPs under near-infrared (NIR) femtosecond laser pulses was demonstrated
      in this study, as positively charged Au@Ag NPs can form aggregates on the
      negatively charged bacterial surface, yielding strong 2PPL emission. The
      aggregation-enhanced 2PPL of Au@Ag NPs stemmed from higher two-photon excitation
      efficiency, implying strong two-photon photothermal effects. Au@Ag NPs showed
      strong antibacterial activity (minimum inhibition concentration as low as 7.5pM
      against Staphylococcus aureus) and negligible toxicity to human dermal
      fibroblasts. Their bactericidal activity was further enhanced under NIR
      irradiation due to strong two-photon photothermal effects. Au@Ag NPs effectively
      removed 85% of the notorious bacterial biofilm within 4 min under NIR
      irradiation. These Au@Ag NPs can potentially be used as imaging and antibacterial
      agents.

PMID- 27697619
TI  - Stratum corneum targeting by dendritic core-multishell-nanocarriers in a mouse
      model of psoriasis.
AB  - Inflammatory disorders of the skin pose particular therapeutic challenges due to
      complex structural and functional alterations of the skin barrier. Penetration of
      several anti-inflammatory drugs is particularly problematic in psoriasis, a
      common dermatitis condition with epidermal hyperplasia and hyperkeratosis. Here,
      we tested in vivo dermal penetration and biological effects of dendritic core
      multishell-nanocarriers (CMS) in a murine skin model of psoriasis and compared it
      to healthy skin. In both groups, CMS exclusively localized to the stratum corneum
      of the epidermis with only very sporadic uptake by Langerhans cells. Furthermore,
      penetration into the viable epidermis of nile red as a model for lipophilic
      compounds was enhanced by CMS. CMS proved fully biocompatible in several in vitro
      assays and on normal and psoriatic mouse skin. The observations support the
      concept of CMS as promising candidates for drug delivery in inflammatory
      hyperkeratotic skin disorders in vivo.

PMID- 27697620
TI  - Preoperative ultrasound staging of the axilla make's peroperative examination of
      the sentinel node redundant in breast cancer: saving tissue, time and money.
AB  - OBJECTIVE: To evaluate the role of preoperative axillary staging with ultrasound
      (US) and fine needle aspiration cytology (FNAC). Can we avoid intraoperative
      sentinel lymph node (SLN) examination, with an acceptable revision rate by
      preoperative staging? DESIGN: This study is based on the retrospective data of
      336 patients that underwent US evaluation of the axilla as part of their staging.
      A FNAC biopsy was performed when abnormal lymph nodes were visualized. Patients
      with normal appearing nodes on US or a benign diagnostic biopsy had removal of
      the SLNs without intraoperative pathological examination. We calculated the
      sensitivity, specificity and accuracy of US/FNAC in predicting the necessity of
      an axillary lymphadenectomy. Subsequently we looked at the total cost and the
      operating time of 3 models. Model A is our study protocol. Model B is a
      theoretical protocol based on the findings of the Z0011 trial with only clinical
      preoperative staging and in Model C preoperative staging and intraoperative
      pathological examination were both theoretically done. sentinel node, staging,
      ultrasound, preoperative axillary staging, FNAC, axilla RESULTS: The sensitivity,
      specificity and accuracy are respectively 0.75 (0.66-0.82), 1.00 (0.99-1.00) and
      0.92 (0.88-0.94). Only 26 out of 317 (8.2%) patients that successfully underwent
      staging needed a revision. The total cost of Model A was 1.58% cheaper than Model
      C and resulted in a decrease in operation time by 9,46%. The benefits compared
      with Model B were much smaller. CONCLUSION: Preoperative US/FNAC staging of the
      axillary lymph nodes can avoid intraoperative examination of the sentinel node
      with an acceptable revision rate. It saves tissue, reduces operating time and
      decreases healthcare costs in general.

PMID- 27697621
TI  - The effects of uterine artery embolization on ovarian reserve.
AB  - OBJECTIVE: To evaluate the effects of UAE for symptomatic uterine fibroids on
      ovarian reserve based on AMH. STUDY DESIGN: This was a retrospective study
      conducted between March 2011 and October 2014. All women underwent UAE. At
      baseline and at the 3-month and 12-month follow-up visits, serum anti-Mullerian
      hormone (AMH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and
      estradiol (E2) levels were assessed, and ovarian volume and antral follicle count
      (AFC) were evaluated in each patient. RESULTS: There were no statistically
      significant differences in serum E2, LH, or FSH levels or in ovarian volume 3 or
      12 months after UAE (P=0.8194, P=0.3976, P=0.4766, and P=0.6822, respectively).
      However, AMH and AFC were significantly different 3 and 12 months after the
      procedure (P=0.00, P=0.029 and P=0.00, P=0.00, respectively). AMH levels remained
      low after 12 months of follow-up compared to the expected AMH levels. A
      statistically significant recovery of serum AMH at 12 months compared to at 3
      months in those <40 years of age (P=0.00), but not in those >=40 years (P=0.837).
      CONCLUSIONS: Ovarian reserve appears to be affected by UAE in premenopausal
      women. However, younger ovaries (according to biological ovarian age) exhibit a
      greater capacity for recovery after ovarian damage. Therefore, larger studies are
      needed for more conclusive results.

PMID- 27697622
TI  - Labor market consequences of childhood onset type 1 diabetes.
AB  - This paper examines the effect of the onset of Type 1 Diabetes Mellitus (T1DM)
      before 15 years of age on labor market outcomes and contributes to the literature
      on effects of childhood health on adult socioeconomic status. Using national
      Swedish socioeconomic register data 1991-2010 for 2485 individuals born 1972-1978
      with onset of T1DM in 1977-1993, we find that T1DM in childhood has a negative
      effect on labor market outcomes later in life. Part of the T1DM effect is
      channeled through occupational field which may be related to both choice and
      opportunities. Although the magnitude of the effect is only directly
      generalizable to illnesses with similar attributes as T1DM, the results suggest
      that causality in the often observed correlation between health and socioeconomic
      status, at least partly, is explained by an effect running from health to
      earnings. This has implications for research and policy on strategies to reduce
      socioeconomic-related health inequality. Our findings also shed light on
      productivity losses, measured by employment status and earnings due to childhood
      onset T1DM, which have implications for both the individual and society.

PMID- 27697623
TI  - Coronary ischemia: Global trigger of sudden cardiac death.

PMID- 27697624
TI  - Reply to the Editor-Importance of response time of esophageal thermal probes.

PMID- 27697625
TI  - To the Editor- Importance of response time of esophageal thermal probes.

PMID- 27697626
TI  - High nasal resistance is stable over time but poorly perceived in people with
      tetraplegia and obstructive sleep apnoea.
AB  - Obstructive sleep apnoea (OSA) is highly prevalent in people with tetraplegia.
      Nasal congestion, a risk factor for OSA, is common in people with tetraplegia.
      The purpose of this study was to quantify objective and perceived nasal
      resistance and its stability over four separate days in people with tetraplegia
      and OSA (n=8) compared to able-bodied controls (n=6). Awake nasal resistance was
      quantified using gold standard choanal pressure recordings (days 1 and 4) and
      anterior rhinomanometry (all visits). Nasal resistance (choanal pressure) was
      higher in people with tetraplegia versus controls (5.3[6.5] vs. 2.1[2.4]
      cmH2O/L/s, p=0.02) yet perceived nasal congestion (modified Borg score) was
      similar (0.5[1.8] vs. 0.5[2.0], p=0.8). Nasal resistance was stable over time in
      both groups (CV=0.23+/-0.09 vs. 0.16+/-0.08, p=0.2). These findings are
      consistent with autonomic dysfunction in tetraplegia and adaptation of perception
      to high nasal resistance. Nasal resistance may be an important therapeutic target
      for OSA in this population but self-assessment cannot reliably identify those
      most at risk.

PMID- 27697627
TI  - Body weight unloading modifications on frontal plane joint moments, impulses and
      Center of Pressure during overground gait.
AB  - BACKGROUND: Body weight unloading is a common method of gait rehabilitation.
      However, little is known about its effects on the overground gait biomechanical
      parameters which were often confounded by the walking modality (treadmill) or the
      speed variability when subjects walked overground while having to pull the body
      weight unloading system to which they were attached. By designing a mechanical
      device that pulled the system at a constant speed, we were able to assess the
      unique effects of body weight unloading on healthy subjects' kinetics during
      overground gait. METHODS: Fifteen healthy subjects walked overground under three
      (0%, 15%, and 30%) body weight unloading experimental conditions. Kinetic
      measures included hip and knee frontal plane moments and impulses and the foot
      center of pressure. FINDINGS: A significant inverse relationship was shown
      between increased body weight unloading levels (0% to 30%) and a decrease in the
      hip and knee first adduction moments and impulses and an increase in the lateral
      shift of the foot center of pressure. Frontal plane hip and knee kinetic
      curvature patterns remained similar as evidenced by low normalized RMSE under
      paired comparisons of the experimental conditions. INTERPRETATION: Overground
      gait with up to 30% body weight unloading stands out as an efficient method of
      reducing loads on joints without distorting kinetic gait curvature patterns. The
      relationship between increased unloading with decreased hip and knee moments and
      impulses and increased lateral shift of the center of pressure also suggests that
      this shift may be an important diagnostic tool in gait assessment and correction.

PMID- 27697628
TI  - Coxsackievirus B heart infections and their putative contribution to sudden
      unexpected death: An 8-year review of patients and victims in the coastal region
      of Tunisia.
AB  - Coxsackieviruses B (CV B) are known as the most common viral cause of human heart
      infections. Cardiac inflammations contribute to sudden unexpected death (SUD)
      significantly. The diagnosis remains difficult with the traditional diagnostic
      tests and must be substantially improved. This has prompted health professionals
      to seek new diagnostic procedures which may provide important clues regarding
      underlying etiology. The present study is based on patients with infectious heart
      diseases and SUD victims with no relevant pathologies. They were investigated for
      possible CV-B infection. Patients with coronary artery diseases and unnatural
      road and domestic accident victims served as controls. The samples were studied
      for CV-B applying PCR. Histopathology for inflammatory markers,
      immunohistochemistry (IHC) for immune inflammatory cells and the enteroviral VP1
      capsid protein were performed. Overall, 102 patients and 87 SUD victims were
      studied. As controls, 100 patients and 54 SUD unnatural accident victims were
      enrolled. CV-B were detected in 28 patients and 15 SUD victims. The control group
      samples were completely virus negative. Compared to controls, IHC revealed a
      significant presence of T and B lymphocytes within the myocardium. Furthermore,
      enteroviral VP1-capsid protein were detected from samples by IHC. Applying a
      comprehensive combination of methods, our results demonstrate the involvement of
      CV-B in cases of heart infection suggesting they play a significant role in SUD.
      Our results emphasize the importance of opting for a combination of methods.

PMID- 27697629
TI  - Age estimation of Calliphora (Diptera: Calliphoridae) larvae using cuticular
      hydrocarbon analysis and Artificial Neural Networks.
AB  - Cuticular hydrocarbons were extracted daily from the larvae of two closely
      related blowflies Calliphora vicina and Calliphora vomitoria (Diptera:
      Calliphoridae). The hydrocarbons were then analysed using Gas Chromatography-Mass
      Spectrometry (GC-MS), with the aim of observing changes within their chemical
      profiles in order to determine the larval age. The hydrocarbons were examined
      daily for each species from 1day old larvae until pupariation. The results show
      significant chemical changes occurring from the younger larvae to the post
      feeding larvae. With the aid of a multivariate statistical method (Principal
      Component Analysis and Artificial Neural Networks), samples were clustered and
      classified, allowing for the larval age to be established. Results from this
      study allowed larvae to be aged to the day with at worst, 87% accuracy, which
      suggests there is great potential for the use of cuticular hydrocarbons present
      on larvae to give an indication of their age and hence potentially a valuable
      tool for minimum PMI estimations.

PMID- 27697630
TI  - AIC and the challenge of complexity: A case study from ecology.
AB  - Philosophers and scientists alike have suggested Akaike's Information Criterion
      (AIC), and other similar model selection methods, show predictive accuracy
      justifies a preference for simplicity in model selection. This epistemic
      justification of simplicity is limited by an assumption of AIC which requires
      that the same probability distribution must generate the data used to fit the
      model and the data about which predictions are made. This limitation has been
      previously noted but appears to often go unnoticed by philosophers and scientists
      and has not been analyzed in relation to complexity. If predictions are about
      future observations, we argue that this assumption is unlikely to hold for models
      of complex phenomena. That in turn creates a practical limitation for
      simplicity's AIC-based justification because scientists modeling such phenomena
      are often interested in predicting the future. We support our argument with an
      ecological case study concerning the reintroduction of wolves into Yellowstone
      National Park, U.S.A. We suggest that AIC might still lend epistemic support for
      simplicity by leading to better explanations of complex phenomena.

PMID- 27697631
TI  - Buccal absorption of diazepam is improved when administered in bioadhesive
      tablets-An in vivo study in conscious Gottingen mini-pigs.
AB  - Buccal delivery may be clinically beneficial for compounds with a high
      gastrointestinal and hepatic first pass metabolism or in situations where a fast
      systemic absorption is desired. The delivery of a crystalline low soluble
      compounds, e.g. diazepam, may be limited due to the low volume of saliva
      available to facilitate solvation in order to drive the permeation of drug
      through the buccal mucosa. Therefore, the present study investigated the
      potential benefits of administering diazepam either as an amorphous or as a
      crystalline form in mucoadhesive tablets to conscious Gottingen mini-pigs.
      Presentation of the compound in the amorphous form lead to a very fast
      absorption, however, the obtained bioavailability was at the same level observed
      following buccal administration of a commercially immediate release tablet.
      Addition of chitosan, as a mucoadhesive excipient, resulted in a higher absolute
      bioavailability compared to tablets without chitosan. The absorption rate for the
      chitosan-based tablets was significant slower, probably due to the slower
      diffusion of the compound out of the tablet. In vitro release data was able to
      predict the variations in tmax, but otherwise no correlation could be found
      between in vitro and in vivo data.

PMID- 27697633
TI  - Targeted release of transcription factors for cell reprogramming by a natural
      micro-syringe.
AB  - Ectopic expression of defined transcription factors (TFs) for cell fate handling
      has proven high potential interest in reprogramming differentiated cells, in
      particular for regenerative medicine, ontogenesis study and cell based modelling.
      Pluripotency or transdifferentiation induction as TF mediated differentiation is
      commonly produced by transfer of genetic information with safety concerns. The
      direct delivery of proteins could represent a safer alternative but still needs
      significant advances to be efficient. We have successfully developed the direct
      delivery of proteins by an attenuated bacterium with a type 3 secretion system
      that does not require challenging and laborious steps for production and
      purification of recombinant molecules. Here we show that this natural micro
      syringe is able to inject TFs to primary human fibroblasts and cord blood CD34+
      hematopoietic stem cells. The signal sequence for vectorization of the TF Oct4
      has no effect on DNA binding to its nucleic target. As soon as one hour after
      injection, vectorized TFs are detectable in the nucleus. The injection process is
      not associated with toxicity and the bacteria can be completely removed from cell
      cultures. A three days targeted release of Oct4 or Sox2 embryonic TFs results in
      the induction of the core pluripotency genes expression in fibroblasts and CD34+
      hematopoietic stem cells. This micro-syringe vectorization represents a new
      strategy for TF delivery and has potential applications for cell fate
      reprogramming.

PMID- 27697632
TI  - Improving adjuvanticity of quaternized chitosan-based microgels for H5N1 split
      vaccine by tailoring the particle properties to achieve antigen dose sparing
      effect.
AB  - In this study, we developed the quaternized chitosan microgels without chemical
      crosslinking as an adjuvant of H5N1 split vaccine. The microgels with pH
      sensitivity, positive surface charge and good biocompatibility, have been
      demonstrated in favor of enhancing both humoral and cellular immune response.
      However, the detailed mechanism of the chitosan-based microgels to enhance
      antigen specific immune responses remains unclear. Therefore, we prepared the
      quaternized chitosan microgels with well defined quaternization degrees (QDs, 20
      80%) and particle sizes (800nm-5MUm) by the premix membrane emulsification
      technique, and investigated the effect of quaternization degree (QD) and size on
      the adjuvanticity of microgels. Results suggested that microgels with relatively
      smaller size (807nm) and moderate quaternization degree (QD 41% and 60%) were
      favorable for a maximum immune response. The mechanism was studied and explained
      by examining the characteristics of microgels and investigating the stimulation
      of bone-marrow derived dendritic cells (BMDCs). Moreover, they induced
      significantly stronger immune responses at lower antigen doses (known as antigen
      sparing effect) compared to aluminum adjuvant. These data indicated that a
      maximum immune response can be achieved by controlling properties of chitosan
      microgels, which also could serve as a significant guidance for rational design
      of chitosan-based particle adjuvant.

PMID- 27697634
TI  - Accumulation of persistent organic pollutants in consumers of eel from polluted
      rivers compared to marketable eel.
AB  - Globally, many river sediments are seriously contaminated with persistent organic
      pollutants (POPs) known to accumulate in aquatic food. In the Netherlands,
      toxicological risks of human exposure to dioxins and dioxin-like compounds led to
      a ban on eel fishing in the Rhine-Meuse delta. The aim of this study is to
      investigate differences in serum POP levels in consumers of eel from high
      polluted areas and consumers of eel from low-polluted areas or aquaculture. In
      total 80 Dutch men were included, aged 40-70 years, with a habitual eel
      consumption of at least one portion (150 g) per month. Total levels of dioxins
      and dioxin-like compounds were measured in serum of all participants with the DR
      CALUX bioassay, validated with GC-MS. For a subgroup of 38 participants extensive
      POP measurements were performed. We revealed that consumption of eel from
      polluted rivers resulted in 2.5 and up to 10 times increased levels of dioxins
      and polychlorinated biphenyls (PCBs) respectively compared to controls. The
      highest PCB levels were detected for PCB 153, with a median level of 896 ng/g
      lipid and a maximum level of 5000 ng/g lipid in the high-exposed group.
      Furthermore, hydroxylated PCB metabolites (OH-PCBs: sum of 4-OH-CB107, 4-OH
      CB146, 4'-OH-CB172, and 4-OH-CB187) were 8 times higher in men who consumed eel
      from polluted areas, and detected at levels (median 4.5 ng/g ww) reported to
      cause adverse health effects. Also, the majority of the perfluoroalkyl substances
      (PFASs) were significantly higher in consumers of eel from pullulated areas. In
      conclusion, this study is the first to reveal that (past) consumption of eel from
      polluted rivers resulted in high body burdens of dioxins, PCBs, OH-PCBs and
      PFASs. We confirmed the predictions made in a former risk assessment, and the
      high levels of dioxins and dioxin-like compounds as well as the OH-PCBs are of
      health concern.

PMID- 27697635
TI  - Apple pectin: A natural source for cancer suppression in 4T1 breast cancer cells
      in vitro and express p53 in mouse bearing 4T1 cancer tumors, in vivo.
AB  - PURPOSE: Increase in the number of cancer related deaths has made the study on
      developing new drugs and treatments essential. One of the main aims in developing
      new therapies is to use natural resources which have the ability to induce
      apoptosis. Pectin is one of these natural compounds, a complex polysaccharide
      found in apples with anti-cancer properties. The aim of this study was to examine
      anti-cancer properties of pectic acid both in vitro in 4T1 breast cancer cells
      and in vivo using an animal model of breast cancer. EXPERIMENTAL DESIGN: MTT cell
      proliferation assays, double fluorescence staining (acridine orange/ethidium
      bromide) and cell cycle analysis were employed to measure apoptosis in vitro. 4T1
      cells were implanted into female BALB/c mice for in vivo studies. Then tumor
      volumes, histological analysis and immunohistochemical staining of P53 and tunnel
      test were applied to evaluate apoptosis in tumors. RESULTS: The results of in
      vitro studies showed that concentration of 0.1% of pectic acid could induce
      apoptosis, inhibit cell growth (p<0.001) and reduce cell attachment, fragmented
      chromatin, and membrane blebbing as well as blocking the sub-G1 phase (p<0.001).
      In addition, in vivo studies showed that pectic acid could inhibit the
      progression of tumors through over-expression of P53 and increasing the number of
      apoptotic cells. CONCLUSION: Our results demonstrated that pectic acid, a natural
      component of apple, can prevent metastasis in both cancer cell lines and primary
      tumors. This potential effect is mainly due to its ability to induce apoptosis.

PMID- 27697636
TI  - Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F
      cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c
      Jun/p-c-Jun(Ser73) and E-cadherin.
AB  - OBJECTIVE: Annexin A5 (Anxa5) is associated with the progression of some cancers,
      while its role and regulation mechanism in tumor lymphatic metastasis is rarely
      reported. This study aims to investigate the influence of Anxa5 knockdown on the
      malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph
      node metastatic (LNM) potential and the underlying regulation mechanism. METHODS:
      RNA interfering was performed to silence Anxa5 in Hca-F. Monoclonal shRNA-Anxa5-
      Hca-F cells were obtained via G418 screening by limited dilution method.
      Quantitative real-time RT-PCR (qRT-PCR) and Western blotting (WB) were applied to
      measure Anxa5 expression levels. CCK-8, Boyden transwell-chamber and in situ LN
      adhesion assays were performed to explore the effects of Anxa5 on the
      proliferation, migration, invasion and adhesion capacities of Hca-F. WB and qRT
      PCR were used to detect the level changes of key molecules in corresponding
      signal pathways. RESULTS: We obtained two monoclonal shRNA-Anxa5-transfected Hca
      F cell lines with stable knockdowns of Anxa5. Anxa5 knockdown resulted in
      significantly reduced proliferation, migration, invasion and in situ LN adhesion
      potentials of Hca-F in proportion to its knockdown extent. Anxa5 downregulation
      enhanced E-cadherin levels in Hca-F. Moreover, Anxa5 affected Hca-F behaviours
      specifically via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) instead of p38MAPK/c-Jun, Jnk/c
      Jun and AKT/c-Jun pathways. CONCLUSIONS: Anxa5 mediates the in vitro malignant
      behaviours of murine hepatocarcinoma Hca-F cells via ERK2/c-Jun/p-c-Jun(Ser73)
      and ERK2/E-cadherin pathways. It is an important molecule in metastasis
      (especially LNM) and a potential therapeutic target for hepatocarcinoma.

PMID- 27697637
TI  - Possible contributions of thyroid hormone replacement to specific behaviors of
      cancer.
AB  - l-Thyroxine (T4) is the principal replacement hormone for patients who have
      hypothyroidism. Some preclinical and clinical evidence supports the possibility
      that T4 can at least permissively affect certain features of established cancers
      and cancer-relevant angiogenesis. Thus, in the occasional patient with
      hypothyroidism and concomitant cancer, it appears reasonable to consider thyroid
      hormone replacement exclusively with 3,3',5-triiodo-l-thyronine (T3). This use of
      T3 has been shown to be effective and safe in early experience with medical
      induction of euthyroid hypothyroxinemia in patients with advanced solid tumors.

PMID- 27697638
TI  - Suppression of lymphangiogenesis by soluble vascular endothelial growth factor
      receptor-2 in a mouse lung cancer model.
AB  - The vascular endothelial growth factor (VEGF) family has a key role in the
      formation of blood vessels and lymphatics. Among the members of this family, VEGF
      C is one of the most important factors involved in lymphangiogenesis via binding
      with two receptors (vascular endothelial growth factor receptor-2 and -3: VEGFR-2
      and VEGFR-3). Soluble VEGFR-2 (sVEGFR-2) has a role in maintaining the alymphatic
      state of the cornea associated with binding to VEGF-C, and selectively inhibits
      lymphangiogenesis but not angiogenesis. In this study, we introduced sVEGFR-2
      into lung cancer cells and evaluated the influence on tumor progression and on
      genes regulating lymphatic formation and metastasis in vivo. A retroviral vector
      was used to introduce the sVEGFR-2 gene into Lewis lung carcinoma cells (LLC),
      which were designated as LLC-sVEGFR-2 cells. Proteins secreted into the culture
      supernatant by these cells were detected by western blotting using specific
      antibodies. To examine lymphangiogenesis by primary lung cancer in vivo, LLC
      sVEGFR-2 cells were subcutaneously injected into C57BL/6 mice. At 14days after
      injection, immunohistochemistry was performed using an antibody directed against
      lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a marker of
      lymphatics. Expression of mRNA for VEGFR-2, VEGFR-3 and matrix metalloproteinases
      (MMPs) was also determined by real-time PCR. Furthermore, LLC-sVEGFR-2 cells were
      directly inoculated into the left lung in C57BL/6 mice and the number of micro
      metastases in pulmonary lymph nodes was determined. Introduction of sVEGFR-2 into
      LLC cells resulted in secretion of sVEGFR-2 protein into the culture supernatant.
      There were fewer LYVE-1 positive lymphatics after inoculation of LLC-sVEGFR-2
      into mice compared with the control group. In addition, VEGFR-2, VEGFR-3, and
      MMPs gene expression was suppressed in the primary tumors of the LLC-sVEGFR-2
      group compared with the control group. Furthermore, there were fewer micro
      metastases in the pulmonary lymph nodes of the LLC-sVEGFR-2 group compared with
      the control group after cells were directly inoculated into the lung. These
      findings indicate that introduction of sVEGFR-2 suppressed lymphangiogenesis in
      primary lung cancer and also suppressed lymphogenic metastasis by inhibiting VEGF
      C, followed by down-regulation of VEGFR-2, VEGFR-3 and MMPs. Accordingly, sVEGFR
      2 might be a promising target for treatment of cancer by regulating
      lymphangiogenesis and lymphogenic metastasis.

PMID- 27697639
TI  - Effect of notch1,2,3 genes silicing on NF-kappaB signaling pathway of macrophages
      in patients with atherosclerosis.
AB  - BACKGROUND: Notch and NF-kappaB signaling pathways both play important roles in
      the regulation of atherosclerosis (AS). However, the mechanisms of notch and NF
      kappaB signaling pathways on AS are still unclear. In this study, we aimed to
      investigate the effects of notch1,2,3 genes silicing by siRNA on notch and NF
      kappaB signaling pathways of macrophages in patients with atherosclerosis (AS),
      so as to seek the treatment of AS from genetic perspective. METHODS: Peripheral
      blood mononuclears of 31 patients with AS were isolated by density gradient
      centrifugation and transformed by PMA to macrophages. Then macrophages were
      transfected with notch1-siRNA (notch1-siRNA group), notch2-siRNA (notch2-siRNA
      group), notch3-siRNA (notch3-siRNA group), negative control siRNA (NC group) and
      none (control group). RT-PCR and Western blot analysis were applied to assess the
      expression level of Delta-like-4 (DLL4), Jagged-1 (JAG1), IkappaBalpha and P52.
      Electrophoretic mobility shift assay (EMSA) was used to observe the NF-kappaB DNA
      binding activity. Subcellular distributions of NF-kappaB/P52 were detected
      through immunofluorescence. mRNA expression levels of TNF-alpha, IL-6 and IL-6 in
      macrophages were also determined with RT- PCR. The expression of 20S proteasome
      was detected by Western blot. RESULTS: After transfected with siRNA, there was no
      difference in the expression of DLL4, JAG1, IkappaBalpha and P52 between NC group
      and control group (p>0.05). Compared with NC group and control group, the
      expression of DLL4, P52 and JAG1 in notch1-siRNA group, notch2-siRNA group and
      notch3-siRNA group was significantly downregulated (p<0.05 or p<0.01,
      respectively), whereas the expression of IkappaBalpha was significantly increased
      (P<0.05 or p<0.01, respectively), especially in notch1-siRNA group. The binding
      activity of NF-kappaB DNA was lower in notch1- siRNA group, notch2-siRNA group
      and notch3-siRNA group compared with NC group and control group (p<0.05),
      especially in notch1-siRNA group. The fluorescence intensity of p52 was decreased
      significantly both in the nucleus and cytoplasm in notch1-siRNA group, notch2
      siRNA group and notch3-siRNA group compared with NC group and control group
      (p<0.05), which decreased more obviously in the nucleus, especially in notch1
      siRNA group. The TNF-alpha, IL-1 and IL-6 expression of notch1-siRNA group,
      notch2-siRNA group and notch3-siRNA group was lower compared to NC group and
      control group (p<0.05 or p<0.01, respectively), also especially in notch1-siRNA
      group. 20S proteasome level was significantly lower in notch1-siRNA group, notch2
      siRNA group and notch3-siRNA group than in NC group and control group (p<0.05 or
      p<0.01, respectively), especially in notch1-siRNA group. CONCLUSIONS: There was a
      positive regulation between Notch and NF-kappaB signaling pathway in patients
      with AS. Notch1 may play a more important role than notch2 and notch 3 in the
      regulation of NF-kappaB signaling pathway in AS.

PMID- 27697641
TI  - Risk of infections during the first year of life after in utero exposure to drugs
      acting on immunity: A population-based cohort study.
AB  - The aim of the study was to evaluate the association between in utero exposure to
      drugs that potentially exhibit immunosuppressive activity and occurrence of
      infections during the first year of life. We conducted a cohort study on the
      prescription data of pregnant women and their children registered in EFEMERIS
      cohort (France), during a one-year period. We classified in utero child exposure
      according to the number of reimbursements for immunosuppressive drugs during
      pregnancy. The number of infectious episodes during the first year of life was
      estimated through the number of anti-infective drugs dispensed. The association
      was estimated by a quasi-Poisson regression with adjustment for confounders. The
      study population consisted of 9614 children, 3141 of whom had been exposed to
      immunosuppressive drugs during pregnancy. The most frequently immunosuppressive
      drugs prescribed were corticosteroids. The mean number of infectious episodes
      during the first year after birth gradually increased with the number of
      immunosuppressive drugs dispensed during pregnancy (from 2.38 in controls to 3.88
      in the most exposed group). After adjustment for potential confounders, in utero
      exposure to immunosuppressive drugs was significantly associated with the number
      of infectious episodes during the first year of life (RR
      3ormoreexposuresVS0=1.35, 95% CI 1.24-1.46). Intrauterine exposure to potentially
      immunosuppressive drugs could be associated with an increased susceptibility to
      infections in early childhood.

PMID- 27697640
TI  - Annexin A2, up-regulated by IL-6, promotes the ossification of ligament
      fibroblasts from ankylosing spondylitis patients.
AB  - BACKGROUND: Annexin A2, a calcium-dependent phospholipid binding protein, is
      involved in osteogenesis. The objective of the present study was to explore the
      expression of Annexin A2 in spinal ligament tissues (LT) of ankylosing
      spondylitis (AS) patients and determine its pathological functions. METHODS: mRNA
      and protein expression of Annexin A2 was detected by real-time PCR and Western
      blotting, respectively. Interleukin-6 (IL-6) concentration in serum was assessed
      by enzyme linked immunosorbent assay. Alkaline phosphatase (ALP) activity was
      measured with ALP activity kit on a microplate reader. RESULTS: mRNA and protein
      expression of Annexin A2 in LT, and IL-6 concentration in serum were
      significantly increased in AS patients. Moreover, exogenous IL-6 treatment
      significantly up-regulated Annexin A2 expression and ALP activity. Silencing of
      Annexin A2 expression significantly ameliorated IL-6-induced ossification of
      fibroblasts from AS patients, as indicated by ALP activity, expression of
      proteins associated with osteogenic differentiation, including bone morphogenetic
      protein-2, osteocalcin and osterix, and the ratio of osteoprotegerin to receptor
      activator of NF-kappaB ligand. Further MEK inhibitor experiments suggested that
      Annexin A2 may exert its function through extracellular signal-related kinase
      pathway. CONCLUSIONS: Annexin A2, up-regulated by IL-6, may promote ligament
      ossification of AS patients.

PMID- 27697642
TI  - Forty years later: Mitochondria as therapeutic targets in muscle diseases.
AB  - The hypothesis that mitochondrial dysfunction can be a general mechanism for cell
      death in muscle diseases is 40 years old. The key elements of the proposed
      pathogenetic sequence (cytosolic Ca2+ overload followed by excess mitochondrial
      Ca2+ uptake, functional and then structural damage of mitochondria, energy
      shortage, worsened elevation of cytosolic Ca2+ levels, hypercontracture of muscle
      fibers, cell necrosis) have been confirmed in amazing detail by subsequent work
      in a variety of models. The explicit implication of the hypothesis was that it
      "may provide the basis for a more rational treatment for some conditions even
      before their primary causes are known" (Wrogemann and Pena, 1976, Lancet, 1, 672
      674). This prediction is being fulfilled, and the potential of mitochondria as
      pharmacological targets in muscle diseases may soon become a reality,
      particularly through inhibition of the mitochondrial permeability transition pore
      and its regulator cyclophilin D.

PMID- 27697643
TI  - Berberine and inflammatory bowel disease: A concise review.
AB  - Berberine is the principal component of many popular medicinal plants (e.g. the
      genus Berberis, Coptis and Hydrastis among others) with a history of thousands of
      years of usage in traditional medicine. The numerous pharmacological activities
      of berberine reported in the last two decades have been attracting high level
      interests both within the scientific community, clinicians and the public at
      large. Despite enormous amount of efforts have been placed to show its
      therapeutic value for inflammatory bowel diseases (IBD), however, comprehensive
      up-to-date review article in this field is not yet available. In this
      communication, literature data from in vitro and in vivo experiments were
      scrutinised and concisely presented to demonstrate its anti-IBD potential. Beyond
      the known general antioxidant and anti-inflammatory effects of berberine, IBD
      specific effects including gut epithelial barrier pathology, T cells as emerging
      targets, antinociceptive and other effects are discussed.

PMID- 27697644
TI  - Epigenetic regulation of active Chinese herbal components for cancer prevention
      and treatment: A follow-up review.
AB  - Epigenetic modifications include DNA methylation, histone modification, and other
      patterns. These processes are associated with carcinogenesis and cancer
      progression. Thus, epigenetic modification-related enzymes, such as DNA
      methyltransferases (DNMTs), histone methyltransferases (HMTs), histone
      demethylases (HDMTs), histone acetyltransferases (HATs), and histone deacetylases
      (HDACs), as well as some related proteins, including methyl-CpG binding proteins
      (MBPs) and DNMT1-associated protein (DMAP 1), are considered as potential targets
      for cancer prevention and therapy. Numerous natural compounds, mainly derived
      from Chinese herbs and chemically ranging from polyphenols and flavonoids to
      mineral salts, inhibit the growth and development of various cancers by targeting
      multiple genetic and epigenetic alterations. This review summarizes the
      epigenetic mechanisms by which active compounds from Chinese herbs exert their
      anti-cancer effect. A subset of these compounds, such as curcumin and
      resveratrol, affect multiple epigenetic processes, including DNMT inhibition,
      HDAC inactivation, MBP suppression, HAT activation, and microRNA modulation.
      Other compounds also regulate epigenetic modification processes, but the
      underlying mechanisms and clear targets remain unknown. Accordingly, further
      studies are required.

PMID- 27697645
TI  - Dibenzo[b,f][1,4]oxazepines and dibenzo[b,e]oxepines: Influence of the chlorine
      substitution pattern on the pharmacology at the H1R, H4R, 5-HT2AR and other
      selected GPCRs.
AB  - Inspired by VUF6884 (7-Chloro-11-(4-methylpiperazin-1
      yl)dibenzo[b,f][1,4]oxazepine), reported as a dual H1/H4 receptor ligand (pKi:
      8.11 (human H1R (hH1R)), 7.55 (human H4R (hH4R))), four known and 28 new
      oxazepine and related oxepine derivatives were synthesised and pharmacologically
      characterized at histamine receptors and selected aminergic GPCRs. In contrast to
      the oxazepine series, within the oxepine series, the new compounds showed high
      affinity to the hH1R (pKi: 6.8-8.7), but no or moderate affinity to the hH4R
      (pKi:<=5.3). For one oxepine derivative (1-(2-Chloro-6,11
      dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine), the enantiomers were
      separated and the R-enantiomer was identified as the eutomer at the hH1R (pKi:
      8.83 (R), 7.63 (S)) and the guinea-pig H1R (gpH1R) (pKi: 8.82 (R), 7.41 (S)).
      Molecular dynamic studies suggest that the tricyclic core of the compounds is
      bound in a similar mode into the binding pocket, as described for doxepine in the
      hH1R crystal structure. Moreover, docking studies of all oxepine derivatives at
      the hH1R indicate that the oxygen and the position of the chlorine in the
      tricyclic core determines, if the R- or the S-enantiomer is the eutomer. For some
      of the oxazepines and oxepines the affinity to other aminergic GPCRs is in the
      same range as to hH1R or hH4R, thus, those compounds have to be classified as
      dirty drugs. However, one oxazepine derivative (3,7-Dichloro-11-(4
      methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine was identified as dual hH1/h5
      HT2A receptor ligand (pKi: 9.23 (hH1R), 8.74 (h5-HT2AR), <=7 at other analysed
      GPCRs), whereas one oxepine derivative (1-(3,8-Dichloro-6,11
      dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine) was identified as selective
      hH1R antagonist (pKi: 8.44 (hH1R), <=6.7 at other analyzed GPCRs). Thus, the
      pharmacological results suggest that the oxazepine/oxepine moiety and
      additionally the chlorine substitution pattern toggles receptor selectivity and
      specificity.

PMID- 27697646
TI  - Efficacy and risk profile of anti-diabetic therapies: Conventional vs traditional
      drugs-A mechanistic revisit to understand their mode of action.
AB  - An increasing array of anti-diabetic drugs are available today, yet Type-2
      diabetes mellitus (T2DM) - remains a life threatening disease, causing high
      mortality and morbidity in developing and developed countries. As of now, no
      effective therapy is available for the complete eradication/cure of diabetes and
      its associated complications. Therefore, it is time to re-think and revisit
      molecular pathways and targets of each existing drug in order to identify
      multiple targets from different signaling pathways that may be manipulated
      simultaneously to treat or manage T2DM effectively. Bearing this goal in mind,
      the article reviews the mechanisms of action of available anti-diabetic drugs
      with in-depth mechanistic analysis of each therapy. The conventional and herbal
      strategies are analysed and compared for their benefits and the associated
      possible side effects. This critical information is necessary not only for the
      development of better, novel and potent anti-diabetic therapy in future but also
      for best possible combinational therapies and strategies with the available
      drugs.

PMID- 27697647
TI  - Prevalence and prevention of cardiovascular disease and diabetes mellitus.
AB  - Noncommunicable diseases (NCDs) have become important causes of mortality on a
      global scale. According to the report of World Health Organization (WHO), NCDs
      killed 38 million people (out of 56 million deaths that occurred worldwide)
      during 2012. Cardiovascular diseases accounted for most NCD deaths (17.5 million
      NCD deaths), followed by cancers (8.2 million NCD deaths), respiratory diseases
      (4.0 million NCD deaths) and diabetes mellitus (1.5 million NCD deaths).
      Globally, the leading cause of death is cardiovascular diseases; their prevalence
      is incessantly progressing in both developed and developing nations. Diabetic
      patients with insulin resistance are even at a greater risk of cardiovascular
      disease. Obesity, high cholesterol, hypertriglyceridemia and elevated blood
      pressure are mainly considered as major risk factors for diabetic patients
      afflicted with cardiovascular disease. The present review sheds light on the
      global incidence of cardiovascular disease and diabetes mellitus. Additionally,
      measures to be taken to reduce the global encumbrance of cardiovascular disease
      and diabetes mellitus are highlighted.

PMID- 27697648
TI  - Magnetic core-shell hybrid nanoparticles for receptor targeted anti-cancer
      therapy and magnetic resonance imaging.
AB  - Hybrid nanoparticles with magnetic poly (lactide-co-glycolide) (PLGA)
      nanoparticle 'core', surface modified with folate-chitosan (fol-cht) conjugate
      'shell' are evaluated as simultaneous anti-cancer therapeutic and MRI contrast
      agent. The fol-cht conjugate is prepared using carbodiimide crosslinking
      chemistry at an optimized folate to amine (chitosan) molar ratio for further
      coating on PLGA nanoparticles loaded with docetaxel and well packed super
      paramagnetic iron oxide nanoparticles (SPIONs). Apart from possessing a targeting
      moiety, the coating provides a physical barrier to avoid undesired burst release
      of drug and also imparts sensitivity to acidic pH, due to protonated amine group
      dependent decondensation of the coating and subsequent drug release. The
      biocompatible hybrid nanoparticles provide receptor targeted docetaxel and SPION
      delivery for anti-cancer therapy and magnetic resonance (MR) imaging
      respectively, as tested in both folate receptor positive and negative cancer
      cells. Enhancement in nanoparticle uptake by folate receptor positive oral cancer
      cells caused significant increase in docetaxel mediated cytotoxicity. While
      polymeric encapsulation and fol-cht coating negatively affects the magnetic
      property of iron oxide nanoparticles, their aggregation in the core, shortened
      the overall T2 relaxation time thereby enhancing the nanoparticle relaxivity to
      provide better in vitro MR imaging.

PMID- 27697649
TI  - Enhancing the upconversion luminescence and photothermal conversion properties of
      ~800nm excitable core/shell nanoparticles by dye molecule sensitization.
AB  - Upconversion nanoparticles capable of strongly absorbing photons in a wide
      spectral range are highly desired for practical applications. In this work, IR
      806 dye was used to increase the light absorptivity of Nd3+/Yb3+/Er3+ tri-doped
      core/shell nanoparticles and then to enhance their upconversion luminescence
      under ~800nm excitation. The IR-806 dye exhibited more efficient energy transfer
      to Nd3+ ions than to Yb3+ ions for subsequent upconversion emission due to the
      increased spectral overlap between the dye emission and Nd3+ absorption. The
      influence of the Nd3+ concentration in the shell and the dye/nanoparticle ratio
      on the dye-sensitization effect was also investigated. A maximum 28-fold overall
      enhancement in the emission intensity was achieved for
      NaYF4:Yb3+/Er3+@NaYF4:Yb3+/Nd3+ core/shell nanoparticles using dye sensitization.
      The dye-sensitized NaYF4:Yb3+/Er3+@NaYF4:Yb3+/Nd3+ core/shell nanoparticles also
      exhibited increased photothermal conversion capabilities and excellent
      temperature sensing properties, enabling their potential application in
      photothermal nanoheaters with real-time temperature monitoring under 808nm single
      beam excitation.

PMID- 27697651
TI  - Magnetic core-shell ZnFe2O4/ZnS nanocomposites for photocatalytic application
      under visible light.
AB  - Magnetic core-shell ZnFe2O4/ZnS composites were synthesized through a two-step
      chemical process including the hydrothermal and the co-precipitation methods. The
      structural characterization revealed that the composites consisted of a layer of
      ZnS clusters on the surface of ZnFe2O4 nanoparticles. The band gap energy of the
      composite was estimated to be 2.2eV through the Kubelka-Munk plot, implying the
      possible application as a photocatalyst under the visible light radiation. The
      improved photocatalytic efficiency of the ZnFe2O4/ZnS composites was confirmed
      through the photocatalytic degradation of Methyl Orange. The increased absorption
      of the visible light and the enhanced separation of the electron-hole pairs due
      to the relative energy band positions in ZnFe2O4 and ZnS are considered as the
      main advantages. Additionally, the moderate magnetization of the ZnFe2O4 core
      insured the easy magnetic collection of the composite materials without affecting
      the photocatalytic performance. Our results showed that ZnFe2O4-based
      nanocomposites could be used as an effective and magnetic retrievable
      photocatalyst.

PMID- 27697650
TI  - Functionalization of mixed ligand metal-organic frameworks as the transport
      vehicles for drugs.
AB  - We reported the design and synthesis of mixed ligands Cu-metal organic frameworks
      (MOFs), MOFs-2 and MOFs-3, and their application as the transport vehicles for
      the delivery of Ibuprofen (IBU) and doxorubicin hydrochloride (DOX). The unique
      MOFs with mixed ligands, 1,3,5-benzene tricarboxylate (BTC) and isophthalic acid
      (IPA), were easily prepared by hydro-thermal method, and their structures were
      well characterized by XRD, FTIR, and SEM imaging analysis. Single ligand MOFs
      with BTC or IPA only were also prepared and characterized as the control group.
      The biocompatibility of synthesized MOFs towards human cells, HEK 293A was
      evaluated by MTT assay. To demonstrate the practical applications of the prepared
      MOFs as the transport vehicles for drugs, the capability of loading and
      controlled release of IBU and DOX by MOFs-1, MOFs-2, MOFs-3, and MOFs-4 were then
      examined. In addition, the drug delivery efficiency of various MOFs with
      different ligands was investigated.

PMID- 27697652
TI  - Development of fluorescent thermoresponsive nanoparticles for temperature
      monitoring on membrane surfaces.
AB  - In this work, tris(phenantroline)ruthenium(II) chloride (Ru(phen)3) was
      immobilized in silica nanoparticles prepared according to the Stober method.
      Efforts were devoted on the optimization of the nano-thermometer in terms of
      size, polydispersity, intensity of the emission and temperature sensitivity. In
      particular, the immobilization of the luminophore in an external thin shell made
      of silica grown in a second step on bare silica nanoparticles allowed producing
      fluorescent monodisperse silica nanoparticles (420+/-20nm). A systematic study
      was addressed to maximize the intensity of the emission of the fluorescent
      nanoparticles by adjusting the concentration of Ru(phen)32+ in the shell from 0.2
      to 24wt.%, whereas the thickness of the shell is affected by the amount of silica
      precursor employed. The luminescent activity of the doped nanoparticles was found
      to be sensitive to the temperature. In fact, the intensity of the emission
      linearly decreased by increasing the temperature from 20 degrees C to 65 degrees
      C. The thermoresponsive nanoparticles were functionalized with long aliphatic
      chains in order to obtain hydrophobic nanoparticles. The developed nanoparticles
      were immobilized via dip-coating procedure on the surface of hydrophobic porous
      membranes, such as Polyvinylidene fluoride (PVDF) prepared via Non-Solvent
      Induced Phase Separation (NIPS), providing local information about the membrane
      surface temperature.

PMID- 27697653
TI  - Biosynthesis, characterization and catalytic activity of Cu/RGO/Fe3O4 for direct
      cyanation of aldehydes with K4[Fe(CN)6].
AB  - This work reports the green synthesis of the Cu/reduced graphene oxide/Fe3O4
      (Cu/RGO/Fe3O4) nanocomposite as a new catalytic system for cyanation of aldehydes
      to nitriles. This nanocomposite catalytic system was synthesized by aqueous
      extract of leaves of Euphorbia bungei Boiss as a reducing and stabilizing agent.
      Various substituted aryl nitrile were prepared under optimized conditions and
      providing moderate to excellent yields. In this process the catalyst exhibited a
      strong magnet response and could be easily separated by an external magnet and
      reused with no loss of catalytic activity.

PMID- 27697654
TI  - Effects of first-row transition metals and impregnation ratios on the
      physicochemical properties of microwave-assisted activated carbons from wood
      biomass.
AB  - First-row transition metals (Co, Ni, Cu and Zn) were successfully used in the
      preparation of activated carbons from wood biomass via microwave-assisted
      irradiation. Physical-chemical properties of the produced materials (MWAC) were
      studied by nitrogen adsorption-desorption curves, SEM, FTIR, UV-vis DRS and
      synchronous fluorescence spectroscopy, CHN elemental analysis, TGA/DTG, pHzpc,
      hydrophobic properties, and total acidity and basicity groups. Results showed
      that the metals were bound successfully in different amounts with surface
      functional groups of the wood biomass through ion exchange and surface
      complexation interaction during the impregnation step. Zn2+ and Cu2+ formed the
      most complexes. MWAC impregnated with Zn2+ showed higher pore volumes and surface
      areas, followed by Cu2+, Co2+ and Ni2+, independently of the ratio used. As the
      metal : biomass ratio was increased from 0.5 to 2, the surface area of MWAC
      increased from 300 to 620m2g-1 for Co-MC, 260 to 381m2g-1 for Ni-MC, 449 to
      765m2g-1 for Cu-MC and from 572 to 1780m2g-1 for Zn-MC. The samples showed high
      values of carbon contents and oxygen-containing groups. An adsorption experiment
      revealed that samples prepared using ZnCl2 showed the highest sorption capacities
      (qe) for the tested adsorbates, followed by CuCl2, CoCl2 and NiCl2. These results
      matched with the surface areas and pore volumes trends, which were found to
      follow atomic number and melting point trends-Ni(II)<Co(II)<Cu(II)<Zn(II), rather
      than the Irving-Williams Series. The sorption capacities (qe) of molecules
      followed this order: 2-nitro phenol>bisphenol A>hydroquinone>4-nitro phenol>2
      naphtol>paracetamol>caffeine>resorcinol.

PMID- 27697655
TI  - Unmet oral health needs among persons with intellectual disability.
AB  - The aim of this study was to examine the factors affecting oral health status
      among intellectually disabled individuals in Serbia. The sample population was
      categorized according to age, sex, living arrangements, general health and the
      level of intellectual disability (ID). The diagnosis of dental caries was
      performed using the DMFT/dmft criteria. The oral hygiene and gingival health were
      assessed with the plaque index (Silness&Loe) and gingival index (Loe&Silness),
      respectively. Descriptive analysis, step-wise and logistic regression were
      performed to analyze related influential factors for caries presence, number of
      extracted teeth, teeth restored, the oral hygiene level and the extent of
      gingival inflammation. Odds ratios for caries were significantly higher among
      adult persons with ID, in persons with co-occurring developmental disorders (DDS)
      and increased with the level of ID. Group with DDS was associated with a 1.6
      times greater odds of untreated decay, while the institutionalization was
      associated with 2.4 times greater odds of untreated decay. Institutionalization
      and co-occurring disabilities have been found to be significantly associated with
      a higher probability of developing gingivitis. Targeting oral health services to
      individuals with ID are encouraged and may help to reduce overall negative effect
      on oral and general health associated with delayed treatments, chronic dental
      pain, emergency dental care, tooth loss and advanced periodontal disease.

PMID- 27697656
TI  - Associations between sleep quality and inflammatory markers in patients with
      schizophrenia.
AB  - Sleep disorder is a risk factor for several systemic inflammation-related
      diseases and there are extensive data showing that schizophrenia is associated
      with chronic low-grade systemic inflammation. This study investigated the
      associations between sleep quality and inflammatory markers in patients with
      schizophrenia, which has not been examined before. Sleep quality (total sleep
      time, sleep efficiency, sleep onset latency, total activity counts, wake after
      sleep onset, number of awakening, and average length of awakening) was measured
      using actigraphy in 199 schizophrenia inpatients. The state of inflammation was
      measured using blood concentration of white blood cells (WBC) and neutrophils,
      together with neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio
      (PLR). The results showed that total sleep time was negatively associated with
      NLR and PLR, and sleep efficiency was negatively associated with neutrophil
      counts and NLR. Sleep onset latency, total activity counts, wake after sleep
      onset, and number of awakening were positively associated with WBC and neutrophil
      counts. The average length of awakening was positively associated with NLR and
      PLR. This is the first report to suggest that improving sleep quality may
      modulate the state of inflammation in patients with schizophrenia.

PMID- 27697657
TI  - Thwarted interpersonal needs and suicide ideation: Comparing psychiatric
      inpatients with bipolar and non-bipolar mood disorders.
AB  - Psychiatric inpatients are at heightened risk for suicide, and evidence suggests
      that psychiatric inpatients with bipolar mood disorders may be at greater risk
      for suicide ideation compared to those with non-bipolar mood disorders. There is
      a paucity of research directly comparing risk factors for suicide ideation in
      bipolar versus non-bipolar mood disorders in an inpatient sample. The current
      study sought to clarify the association between two constructs from the
      interpersonal theory of suicide (i.e., perceived burdensomeness and thwarted
      belongingness) in leading to suicide ideation among psychiatric inpatients with
      bipolar and non-bipolar mood disorders. Participants were (N=90) psychiatric
      inpatients with a bipolar (n = 20) or non-bipolar mood disorder (n=70; per their
      medical charts). Perceived burdensomeness, but not thwarted belongingness, was
      significantly associated with suicide ideation after adjusting for other
      covariates. This suggests perceived burdensomeness may play a key role in suicide
      ideation among psychiatric inpatients with any mood disorder and highlights the
      importance of assessment and intervention of perceived burdensomeness in this
      population. Contrary to our hypothesis, mood disorder group (i.e., bipolar versus
      non-bipolar) did not moderate the relations between perceived
      burdensomeness/thwarted belongingness and suicide ideation.

PMID- 27697659
TI  - An investigation of the speeding-related crash designation through crash
      narrative reviews sampled via logistic regression.
AB  - Speed is one of the most important factors in traffic safety as higher speeds are
      linked to increased crash risk and higher injury severities. Nearly a third of
      fatal crashes in the United States are designated as "speeding-related", which is
      defined as either "the driver behavior of exceeding the posted speed limit or
      driving too fast for conditions." While many studies have utilized the speeding
      related designation in safety analyses, no studies have examined the underlying
      accuracy of this designation. Herein, we investigate the speeding-related crash
      designation through the development of a series of logistic regression models
      that were derived from the established speeding-related crash typologies and
      validated using a blind review, by multiple researchers, of 604 crash narratives.
      The developed logistic regression model accurately identified crashes which were
      not originally designated as speeding-related but had crash narratives that
      suggested speeding as a causative factor. Only 53.4% of crashes designated as
      speeding-related contained narratives which described speeding as a causative
      factor. Further investigation of these crashes revealed that the driver
      contributing code (DCC) of "driving too fast for conditions" was being used in
      three separate situations. Additionally, this DCC was also incorrectly used when
      "exceeding the posted speed limit" would likely have been a more appropriate
      designation. Finally, it was determined that the responding officer only utilized
      one DCC in 82% of crashes not designated as speeding-related but contained a
      narrative indicating speed as a contributing causal factor. The use of logistic
      regression models based upon speeding-related crash typologies offers a promising
      method by which all possible speeding-related crashes could be identified.

PMID- 27697658
TI  - Distance-delivered interventions for PTSD: A systematic review and meta-analysis.
AB  - This systematic review and meta-analysis evaluated the efficacy of distance
      delivered, guided approaches to treatment (e.g., delivered via telephone,
      Internet, mail, videoconferencing) for clinical and subclinical posttraumatic
      stress disorder (PTSD). A comprehensive search yielded 19 randomized controlled
      trials (1491 participants) to be included. Meta-analyses revealed that distance
      delivered interventions led to significant within-group improvements in PTSD
      symptoms at post-treatment (g=0.81, 95% CI 0.65 to 0.97) and 3-6 month follow-up
      (g=0.78, 95% CI 0.59 to 0.97). Within-group depression and quality of life
      outcomes showed similar results, with medium post-treatment and follow-up
      effects. Compared to a waiting list, distance delivery (specifically, Internet
      treatments) led to superior PTSD outcomes (g=0.68, 95% CI 0.51 to 0.86). Compared
      to face-to-face interventions, distance delivery (specifically, videoconferencing
      treatments) did not result in significantly different PTSD outcomes at post
      treatment (g=-0.05, 95% CI -0.31 to 0.20) but led to inferior outcomes at 3-6
      month follow-up (g=-0.25, 95% CI -0.44 to -0.07). Distance delivery of PTSD
      treatment is promising, but research is needed to determine its optimal use.

PMID- 27697660
TI  - Remarkable expression of vascular endothelial growth factor in bone marrow plasma
      cells of patients with POEMS syndrome.
AB  - Vascular endothelial growth factor (VEGF) is pathognomonically elevated in
      patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal
      gammopathy and skin changes) syndrome. However, its source of overproduction is
      unclear. As clinical improvement is almost always associated with VEGF reduction
      after anti-plasma cell therapy, its increase at diagnosis has been attributed to
      the underlying monoclonal gammopathy, although direct evidence is still lacking.
      In the current study, we systemically measured VEGF levels in POEMS patients,
      before and after treatment. Bone marrow plasma cells showed remarkable VEGF
      expression, in both mRNA and protein levels, which decreased gradually in
      response to therapy. Of note, statistically linear correlations were observed
      between serum and bone marrow plasma cell VEGF levels (mRNA vs. serum, rho 0.343,
      p=0.003; protein vs. serum, rho 0.644, p<0.0001), supporting bone marrow plasma
      cells as the main source of circulating VEGF. Intriguingly, immunophenotyping
      revealed that bone marrow plasma cells were polyclonal in most patients at
      diagnosis. A clear monoclonal population, coexistent with polytypic cells, was
      only detectable in 11 cases (18%), in which comparable intracellular VEGF
      expression was observed between these two plasma cell populations (p=0.594),
      while monoclonal cells showed higher intracellular interleukin-6 expression
      (p=0.006). These patients had more serum monoclonal protein, less post
      therapeutic complete remission, and inferior overall (p=0.027) and progression
      free survival (p=0.002). Collectively, bone marrow plasma cells, mainly
      polyclonal population, are the major source of VEGF overproduction in POEMS
      patients.

PMID- 27697662
TI  - An image-invariant neural response to familiar faces in the human medial temporal
      lobe.
AB  - The ability to recognise familiar faces with ease across different viewing
      conditions contrasts with the inherent difficulty in the perception of unfamiliar
      faces across similar image manipulations. Models of face processing suggest that
      this difference is based on the neural representation for familiar faces being
      more invariant to changes in the image, than it is for unfamiliar faces. Here, we
      used an fMR-adaptation paradigm to investigate neural correlates of image
      invariant face recognition in face-selective regions of the human brain.
      Participants viewed faces presented in a blocked design. Each block contained
      different images of the same identity or different images from different
      identities. Faces in each block were either familiar or unfamiliar to the
      participants. First, we defined face-selective regions by comparing the response
      to faces with the response to scenes and scrambled faces. Next, we asked whether
      any of these face-selective regions showed image-invariant adaptation to the
      identity of a face. The core face-selective regions showed image-invariant
      adaptation to familiar and unfamiliar faces. However, there was no difference in
      the adaptation to familiar compared to unfamiliar faces. In contrast, image
      invariant adaptation for familiar faces, but not for unfamiliar faces, was found
      in face-selective regions of the medial temporal lobe (MTL). Taken together, our
      results suggest that the marked differences in the perception of familiar and
      unfamiliar faces may depend critically on neural processes in the medial temporal
      lobe.

PMID- 27697661
TI  - Possible role of intragenic DNA hypermethylation in gene silencing of the tumor
      suppressor gene NR4A3 in acute myeloid leukemia.
AB  - Expression of the tumor suppressor gene NR4A3 is silenced in the blasts of acute
      myeloid leukemia (AML), irrespective of the karyotype. Although the
      transcriptional reactivation of NR4A3 is considered to have a broad-spectrum anti
      leukemic effect, the therapeutic modalities targeting this gene have been
      hindered by our minimal understanding of the transcriptional mechanisms
      regulating its expression, particularly in human AML. Here we show the role of
      intragenic DNA hypermethylation in reducing the expression of NR4A3 in AML.
      Bisulfite sequencing analysis revealed that CpG sites at the intragenic region
      encompassing exon 3 of NR4A3, but not the promoter region, are hypermethylated in
      AML cell lines and primary AML cells. A DNA methyltransferase inhibitor restored
      the expression of NR4A3 following a reduction in DNA methylation levels at
      intragenic CpG sites. The in silico data revealed an enrichment of H3K4me1 and
      H2A.Z at exon 3 of NR4A3 in human non-malignant cells but that was excluded
      specifically in leukemia cells with CpG hypermethylation. This suggests that exon
      3 represents a functional regulatory element involved in the transcriptional
      regulation of NR4A3. Our findings improve the current understanding of the
      mechanism underlying NR4A3 silencing and facilitate the development of NR4A3
      targeted therapy.

PMID- 27697663
TI  - Grasp-specific motor resonance is influenced by the visibility of the observed
      actor.
AB  - Motor resonance is the modulation of M1 corticospinal excitability induced by
      observation of others' actions. Recent brain imaging studies have revealed that
      viewing videos of grasping actions led to a differential activation of the
      ventral premotor cortex depending on whether the entire person is viewed versus
      only their disembodied hand. Here we used transcranial magnetic stimulation (TMS)
      to examine motor evoked potentials (MEPs) in the first dorsal interosseous (FDI)
      and abductor digiti minimi (ADM) during observation of videos or static images in
      which a whole person or merely the hand was seen reaching and grasping a peanut
      (precision grip) or an apple (whole hand grasp). Participants were presented with
      six visual conditions in which visual stimuli (video vs static image), view
      (whole person vs hand) and grasp (precision grip vs whole hand grasp) were varied
      in a 2 * 2 * 2 factorial design. Observing videos, but not static images, of a
      hand grasping different objects resulted in a grasp-specific interaction, such
      that FDI and ADM MEPs were differentially modulated depending on the type of
      grasp being observed (precision grip vs whole hand grasp). This interaction was
      present when observing the hand acting, but not when observing the whole person
      acting. Additional experiments revealed that these results were unlikely to be
      due to the relative size of the hand being observed. Our results suggest that
      observation of videos rather than static images is critical for motor resonance.
      Importantly, observing the whole person performing the action abolished the grasp
      specific effect, which could be due to a variety of PMv inputs converging on M1.

PMID- 27697664
TI  - Mood-congruent recollection and anosognosia in Alzheimer's disease.
AB  - The aim of the study was to investigate experimentally the impact of current mood
      state on anosognosia or awareness of symptoms in AD patients, in which mood state
      was manipulated by giving tasks that were either easy (success condition) or very
      difficult (failure condition). Twenty-two patients with mild to moderate AD
      participated. Four success-failure manipulation (SFM) computerized tasks were
      used as mood induction procedures, two based on reaction time tasks and the other
      on memory tasks. Level of awareness and the current mood state were assessed
      before and after each task, using a modified version of the Anosognosia
      Questionnaire for Dementia and a self-reported questionnaire respectively. For
      both types of task, the results indicate that the emotional state of the
      participants was similar before performing the tasks and that only the failure
      conditions induced a negative mood state. Additionally, regarding the level of
      awareness, there were no significant differences after the reaction time tasks
      but for the memory tasks, there was greater awareness of symptoms after
      performing the task in the failure condition. To the best of our knowledge, this
      study is the first exploring experimentally the impact of mood on anosognosia in
      AD. The results showed an improvement of awareness of symptoms after negative
      mood induction, but only when the task used in the SFM was memory-based.

PMID- 27697665
TI  - Augmenting distractor filtering via transcranial magnetic stimulation of the
      lateral occipital cortex.
AB  - Visual selective attention (VSA) optimizes perception and behavioral control by
      enabling efficient selection of relevant information and filtering of
      distractors. While focusing resources on task-relevant information helps
      counteract distraction, dedicated filtering mechanisms have recently been
      demonstrated, allowing neural systems to implement suitable policies for the
      suppression of potential interference. Limited evidence is presently available
      concerning the neural underpinnings of these mechanisms, and whether neural
      circuitry within the visual cortex might play a causal role in their
      instantiation, a possibility that we directly tested here. In two related
      experiments, transcranial magnetic stimulation (TMS) was applied over the lateral
      occipital cortex of healthy humans at different times during the execution of a
      behavioral task which entailed varying levels of distractor interference and need
      for attentional engagement. While earlier TMS boosted target selection,
      stimulation within a restricted time epoch close to (and in the course of)
      stimulus presentation engendered selective enhancement of distractor suppression,
      by affecting the ongoing, reactive instantiation of attentional filtering
      mechanisms required by specific task conditions. The results attest to a causal
      role of mid-tier ventral visual areas in distractor filtering and offer insights
      into the mechanisms through which TMS may have affected ongoing neural activity
      in the stimulated tissue.

PMID- 27697666
TI  - Case illustration of the difference between bench test and in-vivo scaffold
      fracture thresholds.

PMID- 27697667
TI  - Life-course risk factor levels and coronary artery calcification. The
      Cardiovascular Risk in Young Finns Study.
AB  - BACKGROUND: Risk factors measured in early life have been shown to predict
      coronary artery calcium (CAC) in adulthood. However, limited data exist on when
      risk factor profiles of those who develop CAC diverge from those who do not. We
      investigated the associations of coronary heart disease risk factor trajectories
      beginning in adolescence and CAC measured at middle-age. METHODS: CAC was
      measured among 589 participants aged 39-45years in whom cardiovascular risk
      factors (serum lipids, blood pressure, body mass index, physical activity,
      smoking habits, and fruit, vegetable, fish, and butter intake) had been collected
      in 1980, 1983, 1986, 2001, and 2007 as part of the Cardiovascular Risk in Young
      Finns Study. RESULTS: Mean levels of low-density lipoprotein cholesterol (LDL-C),
      total cholesterol, apolipoprotein B (Apo-B), and systolic blood pressure (SBP)
      levels across the 27-year period were significantly higher among those with CAC
      vs. those without. The difference between the groups was 0.25mmol/l (95%
      confidence interval, 95%CI, 0.079-0.41) for LDL-C, 0.26mmol/l (95%CI 0.080-0.44)
      for total cholesterol, 0.05mmol/l (95%CI 0.0085-0.091) for Apo-B and 1.92mmHg
      (95%CI 0.10-3.74) for SBP after adjustment for other risk factors. Those with CAC
      at age 39-45years had higher serum lipid levels already in adolescence or early
      adulthood compared with those without CAC, with these differences becoming more
      pronounced during the life-course. CONCLUSIONS: Long-time risk factor exposure to
      higher LDL-C, total cholesterol and Apo-B levels already starting in adolescence
      and higher SBP levels in adulthood is associated with CAC at middle-age.

PMID- 27697668
TI  - Brain delivery of microencapsulated GDNF induces functional and structural
      recovery in parkinsonian monkeys.
AB  - Glial cell line-derived neurotrophic factor (GDNF) remains the most potent
      neurotrophic factor for dopamine neurons. Despite its potential as treatment for
      Parkinson's disease (PD), its clinical application has been hampered by safety
      and efficacy concerns associated with GDNF's short in vivo half-life and with
      significant brain delivery obstacles. Drug formulation systems such as
      microparticles (MPs) may overcome these issues providing protein protection from
      degradation and sustained drug release over time. We therefore sought to evaluate
      the efficacy and safety of GDNF delivered via injectable biodegradable MPs in a
      clinically relevant model of PD and to investigate the mechanism contributing to
      their beneficial effects. MPs were injected unilaterally into the putamen of
      parkinsonian monkeys with severe nigrostriatal degeneration. Notably, a single
      administration of the microencapsulated neurotrophic factor achieved sustained
      GDNF levels in the brain, providing motor improvement and dopaminergic function
      restoration. This was reflected by a bilateral increase in the density of
      striatal dopaminergic neurons 9 months after treatment. Moreover, GDNF was
      retrogradely transported to the substantia nigra increasing bilaterally the
      number of dopaminergic and total neurons, regardless of the severe degeneration.
      GDNF-MP injection within the putamen elicited no adverse effects such as
      immunogenicity, cerebellar degeneration or weight loss. MPs are therefore a safe,
      efficient vehicle for sustained protein delivery to the brain, supporting the
      therapeutic benefit of GDNF when encapsulated within MPs for brain repair.
      Overall, these findings constitute important groundwork for GDNF-MP clinical
      development.

PMID- 27697669
TI  - Regenerated silk materials for functionalized silk orthopedic devices by
      mimicking natural processing.
AB  - Silk fibers spun by silkworms and spiders exhibit exceptional mechanical
      properties with a unique combination of strength, extensibility and toughness. In
      contrast, the mechanical properties of regenerated silk materials can be tuned
      through control of the fabrication process. Here we introduce a biomimetic, all
      aqueous process, to obtain bulk regenerated silk-based materials for the
      fabrication of functionalized orthopedic devices. The silk materials generated in
      the process replicate the nano-scale structure of natural silk fibers and possess
      excellent mechanical properties. The biomimetic materials demonstrate excellent
      machinability, providing a path towards the fabrication of a new family of
      resorbable orthopedic devices where organic solvents are avoided, thus allowing
      functionalization with bioactive molecules to promote bone remodeling and
      integration.

PMID- 27697670
TI  - Synergistic antitumor activity of rapamycin and EF24 via increasing ROS for the
      treatment of gastric cancer.
AB  - Mechanistic/mammalian target of rapamycin (mTOR) has emerged as a new potential
      therapeutic target for gastric cancer. Rapamycin and rapamycin analogs are
      undergoing clinical trials and have produced clinical responses in a subgroup of
      cancer patients. However, monotherapy with rapamycin at safe dosage fails to
      induce cell apoptosis and tumor regression which has hampered its clinical
      application. This has led to the exploration of more effective combinatorial
      regimens to enhance the effectiveness of rapamycin. In our present study, we have
      investigated the combination of rapamycin and a reactive oxygen species (ROS)
      inducer EF24 in gastric cancer. We show that rapamycin increases intracellular
      ROS levels and displays selective synergistic antitumor activity with EF24 in
      gastric cancer cells. This activity was mediated through the activation of c-Jun
      N terminal kinase and endoplasmic reticulum stress (ER) pathways in cancer cells.
      We also show that inhibiting ROS accumulation reverses ER stress and prevents
      apoptosis induced by the combination of rapamycin and EF24. These mechanisms were
      confirmed using human gastric cancer xenografts in immunodeficient mice. Taken
      together, our work provides a novel therapeutic strategy for the treatment of
      gastric cancer. The work reveals that ROS generation could be an important target
      for the development of new combination therapies for cancer treatment.

PMID- 27697672
TI  - A computational model for investigating the effects of changes in bioavailability
      of insulin-like growth factor-1 on the homeostasis of the intervertebral disc.
AB  - Insulin-like growth factor-1 (IGF-1) is well-known for upregulating cell
      proliferation and biosynthesis of the extracellular matrix in the intervertebral
      disc (IVD). Pathological conditions, such as obesity or chronic kidney disease
      cause IGF-1 deficiency in plasma. How this deficiency impacts disc homeostasis
      remains unknown. Pro-anabolic approaches for the treatment of disc degeneration
      based on enhancing IGF-1 bioavailability to tissue-cells are considered, but
      knowledge of their effectiveness in enhancing cellular anabolism of a degenerated
      disc is limited. In this study, we developed a computational model for disc
      homeostasis specifically addressing the role of IGF-1 in modulating both
      extracellular matrix biosynthesis and cellularity in the IVD. This model was
      applied to investigate how changes in IGF-1 bioavailability, namely deficiency or
      enhancement of growth factor, affect disc health. In this study, it was found
      that IGF-1 deficiency mainly affects the biosynthesis of ECM components,
      especially in the most external regions of the IVD such as the cartilage
      endplates and the outer portion of annulus fibrosus. Also, a total of three
      approaches for increasing IGF-1 bioavailability as a therapy for degenerated IVDs
      were investigated. It was found that all these strategies are only beneficial to
      those disc regions receiving sufficient nutritional supply (i.e., the outmost IVD
      regions), while they exacerbate tissue degradation in malnourished regions (i.e.,
      inner portion of the disc). This suggests that pro-anabolic growth factor-based
      therapies are limited in that their success strongly depends on an adequate
      nutritional supply to the IVD tissue, which is not guaranteed in degenerated
      discs.

PMID- 27697671
TI  - Reducing risk for anxiety and depression in adolescents: Effects of a single
      session intervention teaching that personality can change.
AB  - Efforts to reduce youth mental health problems have advanced greatly but have not
      lowered overall rates of youth mental illness. Thus, a need exists for
      disseminable, mechanism-targeted approaches to reducing risk of youth
      psychopathology. Accordingly, we conducted a randomized-controlled trial testing
      whether a single-session intervention teaching growth personality mindsets (the
      belief that personality is malleable) reduced known risk factors for anxiety and
      depression in adolescents experiencing or at risk for internalizing problems (N =
      96, ages 12-15). Compared to a supportive-therapy control, a 30-min computer
      guided mindset intervention strengthened adolescents' perceived control; this
      improvement was associated with increases in growth mindsets. Further,
      electrodermal activity recovery slopes showed that youths receiving the mindset
      intervention recovered from a lab-based social stressor over three times as fast
      as control group youths. Improvements in growth mindsets and perceived control
      were linked with faster stress recovery. Results suggest a disseminable strategy
      for reducing internalizing problem risk among adolescents.

PMID- 27697673
TI  - Proteome changes associated with dormancy release of Dongxiang wild rice seeds.
AB  - Seed dormancy provides optimum timing for seed germination and subsequent
      seedling growth, but the mechanism of seed dormancy is still poorly understood.
      Here, we used Dongxiang wild rice (DXWR) seeds to investigate the dormancy
      behavior and the differentially changed proteome in embryo and endosperm during
      dormancy release. DXWR seed dormancy was caused by interaction of embryo and its
      surrounding structure, and was an intermediate physiological dormancy. During
      seed dormancy release, a total of 109 and 97 protein spots showed significant
      change in abundance and were successfully identified in embryo and endosperm,
      respectively. As a result of dormancy release, the abundance of nine proteins
      involved in storage protein, cell defense and rescue and energy changed in the
      same way in both embryo and endosperm, while 67 and 49 protein spots changed
      differentially in embryo and endosperm, respectively. Dormancy release of DXWR
      seeds was closely associated with degradation of storage proteins in both embryo
      and endosperm. At the same time, the abundance of proteins involved in
      metabolism, glycolysis and TCA cycle, cell growth and division, protein synthesis
      and destination and signal transduction increased in embryos while staying
      constant or decreasing in endosperms.

PMID- 27697674
TI  - Levels of the soluble LDL receptor-relative LR11 decrease in overweight
      individuals with type 2 diabetes upon diet-induced weight loss.
AB  - BACKGROUND AND AIMS: Cardiovascular disease (CVD) is a major complication in
      patients with type 2 diabetes (T2D), especially in those with obesity. Plasma
      soluble low density lipoprotein receptor-relative with 11 ligand-binding repeats
      (sLR11) plays a role in the development of atherosclerosis and has been linked to
      the metabolism of triglyceride-rich lipoproteins, adiposity, and vascular
      complications in T2D. We aimed to determine the effect of diet-induced weight
      loss on plasma sLR11 levels in overweight and obese individuals with T2D.
      METHODS: Plasma sLR11 levels were determined in 64 individuals with T2D and BMI
      >27 kg/m2 before and after a 20-week weight loss diet. As a reference, sLR11
      levels were also determined in 64 healthy, non-obese controls, matched as a group
      for age and sex. RESULTS: Median plasma sLR11 levels of the T2D study-group at
      baseline (15.4 ng/mL (IQR 12.9-19.5)) were higher than in controls (10.2 (IQR:
      8.7-12.2) ng/mL; p = 0.001). The diet resulted in a weight loss of 9.7 +/- 5.2%
      (p = 0.001) and improved CVD risk factors. sLR11 levels were reduced to 13.3
      ng/mL (IQR 11.0-17.1; p = 0.001). Changes in sLR11 levels positively associated
      with changes in non-HDL cholesterol (B = 1.54, R2 = 0.17, p = 0.001) and HbA1c (B
      = 0.07, R2 = 0.11, p = 0.007), but not with weight loss (B = 0.04, R2 = 0.05, p =
      0.076). The changes in non-HDL cholesterol and HbA1c together explained 24% of
      the variance of sLR11 reduction (p = 0.001). CONCLUSIONS: Weight loss dieting in
      overweight and obese individuals with T2D resulted in a reduction in plasma sLR11
      levels that was associated with improvements in lipid-profile and glycemic state.

PMID- 27697675
TI  - Goserelin plus tamoxifen compared to chemotherapy followed by tamoxifen in
      premenopausal patients with early stage-, lymph node-negative breast cancer of
      luminal A subtype.
AB  - OBJECTIVES: To study the outcomes of adjuvant goserelin combined with tamoxifen
      (GosTam) compared to chemotherapy followed by tamoxifen (ChemTam) in
      premenopausal patients with early stage, luminal A breast cancer. METHODS: From
      2008 until 2013, data were retrospectively collected for premenopausal patients
      who underwent surgery for invasive tumors that were <=2.0 cm, node-negative,
      strongly positive for estrogen and progesterone receptors, HER-2-negative, and Ki
      67 < 25%. The patients were divided into two groups according to adjuvant
      regimen, either GosTam or ChemTam. All patients who underwent different adjuvant
      regimens were excluded. RESULTS: In total, 235 patients underwent GosTam and 171
      patients underwent ChemTam. There were significantly more patients younger than
      40 years in the GosTam group (32% GosTam vs. 22% ChemTam, p = 0.031). Mean tumor
      size was significantly smaller (1.19 cm vs. 1.48 cm, p < 0.001), Ki-67
      significantly lower (p = 0.049), and nuclear grade was low in a significant
      number of patients in the GosTam group (2% vs. 13%, p < 0.001). After a median
      follow-up of 51.3 months, there was no mortality in either group. There was no
      significant difference in 5-year disease-free survival (DFS) between the two
      groups even after univariate analysis considering age, tumor size, nuclear grade,
      and P53% (GosTam = 98.9% vs. ChemTam = 95.7%, HR = 0.404, 95% CI = [0.073,
      2.222], p = 0.248). CONCLUSION: There was no difference between treatment groups,
      and neither chemotherapy nor ovarian suppression seemed to improve the outcome.
      Thus, tamoxifen alone might be a sufficient option for this low-risk patient
      population.

PMID- 27697676
TI  - A comparison of patient-centered economic and clinical outcomes of post
      mastectomy breast reconstruction between obese and non-obese patients.
AB  - BACKGROUND: The objectives of this study were to compare, by patient obesity
      status, the contemporary utilization patterns of different reconstruction surgery
      types, understand postoperative complication profiles in the community setting,
      and analyze the financial impact on health care payers and patients. METHODS:
      Using data from the MarketScan Health Risk Assessment Database and Commercial
      Claims and Encounters Database, we identified breast cancer patients who received
      breast reconstruction surgery following mastectomy between 2009 and 2012. The
      Cochran-Armitage test was used to evaluate the utilization pattern of breast
      reconstruction surgery. Multivariable logistic regressions were used to estimate
      the association between obesity status and infectious, wound, and perfusion
      complications within one year of surgery. A generalized linear model was used to
      compare total, complication-related, and out-of-pocket costs. RESULTS: The rate
      of TE/implant-based reconstruction increased significantly for non-obese patients
      but not for obese patients during the years analyzed, whereas autologous
      reconstruction decreased for both patient groups. Obesity was associated with
      higher odds of infectious, wound, and perfusion complications after TE/implant
      based reconstruction, and higher odds of perfusion complications after autologous
      reconstruction. The adjusted total healthcare costs and out-of-pocket costs were
      similar for obese and non-obese patients for either type of breast reconstruction
      surgery. CONCLUSIONS: A greater likelihood of one-year complications arose from
      TE/implant-based vs autologous reconstruction surgery in obese patients. Given
      that out-of-pocket costs were independent of the type of reconstruction, greater
      emphasis should be placed on conveying the surgery-related complications to obese
      patients to aid in patient-based decision making with their plastic surgeons and
      oncologists.

PMID- 27697677
TI  - A study of the relationship between the study process, motivation resources, and
      motivation problems of nursing students in different educational systems.
AB  - BACKGROUND: The study process is related to students' learning approaches and
      styles. Motivation resources and problems determine students' internal, external,
      and negative motivation. Analyzing the study process and motivation of students
      yields important indications about the nature of educational systems in higher
      education. OBJECTIVES: This study aims to analyze the relationship between the
      study process, and motivation resources and problems with regard to nursing
      students in different educational systems in Turkey and to reveal their effects
      according to a set of variables. DESIGN: This is a descriptive, cross-sectional
      and correlational study. SETTINGS: Traditional, integrated and problem-based
      learning (PBL) educational programs for nurses involving students from three
      nursing schools in Turkey. PARTICIPANTS: Nursing students (n=330). METHODS: The
      data were collected using the Study Process Questionnaire (R-SPQ-2F) and the
      Motivation Resources and Problems (MRP) Scale. RESULTS: A statistically
      significant difference was found between the scores on the study process scale,
      and motivation resources and problems scale among the educational systems. This
      study determined that the mean scores of students in the PBL system on learning
      approaches, intrinsic motivation and negative motivation were higher. A positive
      significant correlation was found between the scales. CONCLUSIONS: The study
      process, and motivation resources and problems were found to be affected by the
      educational system. This study determined that the PBL educational system more
      effectively increases students' intrinsic motivation and helps them to acquire
      learning skills.

PMID- 27697678
TI  - Nursing students' changing orientation and attitudes towards nursing during
      education: A two year longitudinal study.
AB  - BACKGROUND: Previous studies have shown that nursing students' perceptions of
      nursing change over time. Little research has been undertaken in the Netherlands
      of students entering nursing programmes and of how they progress. OBJECTIVES: The
      aims of this study were to explore whether nursing students' orientation and
      attitudes towards nursing changed over time, when these changes occurred, and
      what factors influenced the changes. We also aimed to identify the factors which
      prompted them to consider leaving their programmes, and what factors affected
      their motivation to stay. DESIGN: The study used a longitudinal quantitative
      design. PARTICIPANTS: Questionnaires were administered to all students enrolled
      in a Bachelor's of Nursing programme at four nursing universities of applied
      sciences in the Netherlands (n=1414). The data for this study were collected
      during the first two years of the programme, from September 2011 to June 2013. A
      total of 123 respondents completed the survey each year and this group was used
      to examine changes over time. METHODS: At four time intervals respondents
      completed a survey consisting of 1) the Nursing Orientation Tool, 2) the Nursing
      Attitude Questionnaire and 3) background characteristics. Non-parametric tests
      were used to explore changes in factor scores over time. RESULTS: The results
      showed an improvement in the students' orientation and attitudes towards
      knowledge, skills and the professional roles of nurses, while empathic behaviour
      decreased over time. Although the changes showed non-linear patterns over time,
      the results showed clear effects between the different time points. The reasons
      for attrition (24%) proved to be related both to problems with the educational
      programme and to personal problems. An important motivator for students to stay
      in the course was their passionate desire to become nurses, suggesting that the
      positive aspects of a nursing career dominated the problems they encountered.
      CONCLUSIONS: Tutors and mentors should pay more attention to the individual
      perceptions and problems of first and second-year students, both in the classroom
      and during clinical placements. Knowledge of the students' perceptions from the
      very beginning could be vital to study success.

PMID- 27697679
TI  - Creating stories for learning about the neonatal care experience through the eyes
      of student nurses: An interpretive, narrative study.
AB  - BACKGROUND: Storytelling is an increasingly well recognised and valued platform
      to learn about the human experience within healthcare. Little is known however
      about how stories can enhance understanding in neonatal care, a specialised field
      offering rich opportunities for learning. This study focuses on the creation of
      stories based on the experiences of student nurses to inform teaching and
      learning strategies in the neonatal field. OBJECTIVES: The study aimed to create
      stories from the narratives of student nurses working within the neonatal field
      and identify what key themes for learning emerged in order to develop a
      storytelling resource to share experiences with their peers. DESIGN: An
      interpretive, constructivist approach was used to collect, analyse and create
      stories from student nurse's experiences, in line with narrative inquiry.
      PARTICIPANTS: Six pre-registration children's nursing students were selected by
      purposive sampling. SETTINGS: Interviews were undertaken within six weeks
      following placement completion in an agreed location. METHODS: Narratives were
      obtained by semi-structured interviews. Narrative analysis and core story
      creation was undertaken to construct stories and key learning themes emerged
      which provided the pedagogical basis for subsequent digital resource development.
      FINDINGS: Key themes emerged relating to the insight and observances of student
      nurses and the neonatal journey they had experienced, including the nature of
      neonatal care, experiences of the neonate and parents, the environment and their
      own learning transition. Preliminary peer evaluation of the storytelling resource
      revealed storytelling as an interesting and novel approach to teaching &
      learning, learning from ones' peers, preparation for practice and a valuable
      insight into a new specialist area. CONCLUSIONS: The study has value to teaching
      and learning by enabling an appreciation of how narrative can be used to portray
      the experiences of learners. Findings also support an approach to analysing
      narrative to create stories for learning and inform subsequent digital resource
      development.

PMID- 27697680
TI  - Developing a vacuum thermal stripping - acid absorption process for ammonia
      recovery from anaerobic digester effluent.
AB  - To prevent acetoclastic methanogens from ammonia inhibition in anaerobic
      digestion of protein-rich substrates, ammonia needs to be removed or recovered
      from digestate. This paper presents an innovative ammonia recovery process that
      couples vacuum thermal stripping with acid absorption. Ammonia is stripped out of
      digestate boiling at a temperature below the normal boiling point due to vacuum.
      Stripped ammonia is absorbed to a sulfuric acid solution, forming ammonium
      sulfate crystals as a marketable product. Three common types of digestate were
      found to have boiling point temperature-vacuum curves similar to water. Seven
      combinations of boiling temperature and vacuum (50  degrees C 16.6 kPa, 58 
      degrees C 20.0 kPa, 65  degrees C 25.1 kPa, 70  degrees C 33.6 kPa, 80  degrees C
      54.0 kPa, 90  degrees C 74.2 kPa, and 100  degrees C 101.3 kPa) were tested for
      batch stripping of ammonia in dairy manure digestate. 93.3-99.9% of ammonia was
      stripped in 3 h. The Lewis-Whitman model fitted ammonia stripping process well.
      Ammonia mass transfer coefficient was significantly higher at boiling temperature
      65-100  degrees C and vacuum pressure 25.1-101.3 kPa than 50-58  degrees C and
      16.6-20.0 kPa. The low ammonia saturation concentrations (0-24 mg N/L) suggested
      a large driving force to strip ammonia. The optimum boiling point temperature -
      vacuum pressure for ammonia recovery in a recirculation line of a mesophilic
      digester was 65  degrees C and 25.1 kPa, at which the ammonia mass transfer
      coefficient was as high as 37.3 mm/h. Installation of a demister and liquid trap
      could avoid negative effects of higher stripping temperature and stronger vacuum
      on formation of ammonium sulfate crystals. Pilot tests demonstrated that high
      purity ammonium sulfate crystals could be produced by controlling sulfuric acid
      content and maintaining acid solution saturated with ammonium sulfate. Although
      volatile organic compounds such as cyclohexene were found in the final acid
      solutions, no volatile organic compounds were found in the recovered crystals.

PMID- 27697681
TI  - Characterization of anaerobic granular sludge using a rheological approach.
AB  - High-rate anaerobic granular sludge reactors have been developed and are widely
      used for wastewater treatment. An accurate estimate of sludge rheological
      properties is required for the design and efficient operation of the digestion
      process. The present work determined the rheological behavior of anaerobic
      granular sludge obtained from a full-scale bioreactor at different solid
      concentrations, operation temperatures and particle sizes, and highlighted common
      features in flow and dynamic measurements. The granular sludge showed a shear
      thinning behavior with a yield stress under flow measurements and a viscoelastic
      property in dynamic measurements. The structure of granules was nearly
      temperature-independent in the range of operational temperature (20-70  degrees
      C), but the total solid concentration and particle size had significant effects
      on not only the rheological properties, but also the operation of the
      bioreactors. In addition, anaerobic granular sludge could cross over from the
      strong-link regime to the weak-link regime as the solid concentration increased.
      Furthermore, we adopted a Wagner-type constitutive model to describe the time
      dependent and non-linear viscoelastic behaviors of anaerobic granular sludge, and
      then evaluated its validity and limitation.

PMID- 27697682
TI  - Polyhydroxyalkanoate synthesis by mixed microbial consortia cultured on fermented
      dairy manure: Effect of aeration on process rates/yields and the associated
      microbial ecology.
AB  - Polyhydroxyalkanoates (PHAs) are biodegradable polymers that can substitute for
      petroleum-based plastics in a variety of applications. One avenue to commercial
      PHA production involves coupling waste-based synthesis with the use of mixed
      microbial consortia (MMC). In this regard, production requires maximizing the
      enrichment of a MMC capable of feast-famine PHA synthesis, with the metabolic
      response induced through imposition of aerobic-dynamic feeding (ADF) conditions.
      However, the concept of PHA production in complex matrices remains unrefined;
      process operational improvements are needed, along with an enhanced understanding
      of the MMC. Research presented herein investigated the effect of aeration on
      feast-famine PHA synthesis, with four independent aeration state systems studied;
      MMC were fed volatile fatty acid (VFA)-rich fermented dairy manure. Regardless of
      the aeration state, all MMC exhibited a feast-famine response based on observed
      carbon cycling. Moreover, there was no statistical difference in PHA synthesis
      rates, with qPHA ranging from 0.10 to 0.19 CmmolPHA gVSS-1 min-1; VFA uptake
      rates exhibited similar statistical indifferences. PHA production assessments on
      the enriched MMC resulted in maximum intracellular concentrations ranging from
      22.5 to 90.7% (mgPHA mgVSS-1); at maximum concentration, the mean hydroxyvalerate
      mol content was 73 +/- 0.6%. While a typical feast-famine dissolved oxygen (DO)
      pattern was observed at maximum aeration, less resolution was observed at
      decreasing aeration rates, suggesting that DO may not be an optimal process
      monitoring parameter. At lower aeration states, nitrogen cycling patterns,
      supported by molecular investigations targeting AOBs and NOBs, indicate that NO2
      and NO3 sustained feast-famine PHA synthesis. Next-generation sequencing analysis
      of the respective MMC revealed numerous and diverse genera exhibiting the
      potential to achieve PHA synthesis, suggesting functional redundancy embedded in
      the diverse MMC. Ultimately, results demonstrate that aeration can be controlled
      in waste-based ADF systems to sustain PHA production potential, while enriching
      for a diverse MMC that exhibits potential functional redundancy. Reduced aeration
      could also enhance cost competitiveness of waste-based PHA production, with
      potential further benefits associated with nitrogen treatment.

PMID- 27697683
TI  - Chloramines in a pilot-scale water distribution system: Transformation of 17beta
      estradiol and formation of disinfection byproducts.
AB  - The degradation and transformation products of 17beta-estradiol (E2) by
      chloramines in a pilot-scale water distribution system (WDS) were investigated
      using varying conditions including multiple mass ratios of chlorine to nitrogen
      (Cl/N), changing concentrations of chloramines, and different pH and pipe
      materials. The degradation of E2 was complete in <=9 h in both deionized water
      (DW) and in the WDS under studied conditions. When the degradation rate of E2 was
      compared in WDS and DW, the degradation rate was appreciably greater in the WDS
      than in the DW at Cl/N mass ratios of 3, 4 and 6. However, at Cl/N mass ratios of
      8 and 9, degradation was faster in the DW than in the WDS. The degradation rate
      of E2 was greatly affected by the initial total chloramine concentration, and the
      degradation of E2 in DW was consistent with second-order kinetics. The
      degradation rate of E2 in both the DW and the WDS increased with increasing pH.
      The order of degradation rate of E2in different pipes was: ductile iron loop
      (loop A) > polyethylene (PE) loop (loop B)> stainless steel loop (loop C). Ten
      specific degradation products of E2, produced by chloramination, were identified.
      Most of the degradation products of E2 chloramination were stable for more than
      10 h. The degradation pathways of E2 in the WDS are proposed and briefly
      discussed. The concentrations of trihalomethanes (THMs), haloacetic acids (HAAs),
      and halogenated nitromethane (HNMs) during the degradation E2 in WDS were also
      determined.

PMID- 27697684
TI  - Distributions, abundances and activities of microbes associated with the nitrogen
      cycle in riparian and stream sediments of a river tributary.
AB  - River tributaries are ecologically important environments that function as sinks
      of inorganic nitrogen. To gain greater insight into the nitrogen cycle (N-cycle)
      in these environments, the distributions and activities of microbial populations
      involved in the N-cycle were studied in riparian and stream sediments of the
      Santa Fe River (SFR) tributaries located in northern Florida, USA. Riparian
      sediments were characterized by much higher organic matter content, and
      extracellular enzyme activities, including cellobiohydrolase, beta-d-glucosidase,
      and phenol oxidase than stream sediments. Compared with stream sediments,
      riparian sediments exhibited significantly higher activities of nitrification,
      denitrification, dissimilatory nitrate reduction to ammonia (DNRA) and anaerobic
      ammonia oxidation; correspondingly, with higher copies of amoA (a biomarker for
      enumerating nitrifiers), nirS and nirK (for denitrifiers), and nrfA (for DNRA
      bacteria). Among N-cycle processes, denitrification showed the highest activities
      and the highest concentrations of the corresponding gene (nirK and nirS) copy
      numbers. In riparian sediments, substantial nitrification activities (6.3 mg-N kg
      soil-1d-1 average) and numbers of amoA copies (7.3 * 107 copies g soil-1 average)
      were observed, and nitrification rates correlate with denitrification rates. The
      guild structures of denitrifiers and nitrifiers in riparian sediments differed
      significantly from those found in stream sediments, as revealed by analysis of
      nirS and archaeal amoA sequences. This study shows that riparian sediments serve
      as sinks for inorganic nitrogen loads from non-point sources of agricultural
      runoff, with nitrification and denitrification associated with elevated levels of
      carbon and nitrogen contents and extracellular enzyme activities.

PMID- 27697685
TI  - Sludge bio-drying: Effective to reduce both antibiotic resistance genes and
      mobile genetic elements.
AB  - Sewage sludge is considered as one of major contributors to the increased
      environmental burden of ARGs. Sludge bio-drying was increasingly adopted due to
      its faster sludge reduction compared with composting. The fate of ARGs during
      full-scale sludge bio-drying was investigated to determine whether it could
      effectively reduce ARGs, and the contributions of bacterial community, horizontal
      gene transfer (HGT) through mobile genetic elements (MGEs) and co-selection from
      heavy metals to ARGs profiles were discussed in detail. Two piles with different
      aeration strategies (Pile I, the improved and Pile II, the control) were operated
      to elucidate effects of aeration strategy on ARGs profiles. Results showed that
      sludge bio-drying could effectively reduce both most of targeted ARGs (0.4-3.1
      logs) and MGEs (0.8-3.3 logs) by the improved aeration strategy, which also
      enhanced both the sludge bio-drying performance and ARGs reduction. The
      enrichment of ARGs including ermF, tetX and sulII could be well explained by the
      evolution of bioavailable heavy metals, not HGT through MGEs, and their potential
      host bacteria mainly existed in Bacteroidetes. Although changes of bacterial
      community contributed the most to ARGs profiles, HGT through MGEs should be paid
      more attention especially in the thermophilic stage of sludge bio-drying.

PMID- 27697686
TI  - Impact of fulvic acids on bio-methanogenic treatment of municipal solid waste
      incineration leachate.
AB  - A considerable amount of leachate with high fulvic acid (FA) content is generated
      during the municipal solid waste (MSW) incineration process. This incineration
      leachate is usually processed by downstream bio-methanogenic treatment. However,
      few studies have examined the impact that these compounds have on methanogenesis
      and how they are degraded and transformed during the treatment process. In this
      study, a laboratory-scale expanded granular sludge bed (EGSB) reactor was
      operated with MSW incineration leachate containing various concentrations of FA
      (1500 mg/L to 8000 mg/L) provided as the influent. We found that FA degradation
      rates decreased from 86% to 72% when FA concentrations in the reactor were
      increased, and that molecular size, level of humification and aromatization of
      the residual FA macromolecules all increased after bio-methanogenic treatment.
      Increasing FA influent concentrations also inhibited growth of hydrogenotrophic
      methanogens from the genus Methanobacterium and syntrophic bacteria from the
      genus Syntrophomonas, which resulted in a decrease in methane production and a
      concomitant increase in CO2 content in the biogas. Sequences most similar to
      species from the genus Anaerolinea went up as FA concentrations increased.
      Bacteria from this genus are capable of extracellular electron transfer and may
      be using FA as an electron acceptor for growth or as a shuttle for syntrophic
      exchange with other microorganisms in the reactor. In order to determine whether
      FA could serve as an electron shuttle to promote syntrophy in an anaerobic
      digester, co-cultures of Geobacter metallireducens and G. sulfurreducens were
      grown in the presence of FA from raw leachate or from residual bioreactor
      effluent. While raw FA stimulated electron transfer between these two bacteria,
      residual FA did not have any electron shuttling abilities, indicating that FA
      underwent a significant transformation during the bio-methanogenic treatment
      process. These results are significant and should be taken into consideration
      when optimizing anaerobic bioreactors used to treat MSW incineration leachate
      high in FA content.

PMID- 27697687
TI  - Drivers of nitrous oxide accumulation in denitrification biofilters with low
      carbon:nitrogen ratios.
AB  - Heterotrophic denitrification is usually inhibited by insufficient carbon
      sources; however, the underlying mechanisms responsible for nitrous oxide (N2O)
      accumulation within denitrification at low carbon:nitrogen (C/N) ratios have not
      been quantified from a molecular level. In this study, five denitrification
      biofilters were developed and exhibited efficiency (total nitrogen: 18.5%-92.2%;
      nitrate nitrogen: 42.9%-99.5%; chemical oxygen demand: 50.5%-93.7%) in
      remediating micro-polluted water with C/N ratios ranging between 0.65 and 3.0. A
      combined analysis revealed that the coupling of anaerobic ammonium oxidation
      (ANAMMOX) and denitrification accounted for N2O accumulation in the biofilters,
      and the key drivers of the N2O accumulation rates were qnorB/nirK, nosZ/(narG +
      napA), amx/(nirS + nirK), narG/bacteria and qnorB/bacteria. Our study
      demonstrated that genetic association was indicative of microbial processes
      relative to nitrogen cycling and reflected N2O flux within denitrification
      biofilters at low C/N ratios.

PMID- 27697688
TI  - Biofouling in forward osmosis systems: An experimental and numerical study.
AB  - This study evaluates with numerical simulations supported by experimental data
      the impact of biofouling on membrane performance in a cross-flow forward osmosis
      (FO) system. The two-dimensional numerical model couples liquid flow with solute
      transport in the FO feed and draw channels, in the FO membrane support layer and
      in the biofilm developed on one or both sides of the membrane. The developed
      model was tested against experimental measurements at various osmotic pressure
      differences and in batch operation without and with the presence of biofilm on
      the membrane active layer. Numerical studies explored the effect of biofilm
      properties (thickness, hydraulic permeability and porosity), biofilm membrane
      surface coverage, and biofilm location on salt external concentration
      polarization and on the permeation flux. The numerical simulations revealed that
      (i) when biofouling occurs, external concentration polarization became important,
      (ii) the biofilm hydraulic permeability and membrane surface coverage have the
      highest impact on water flux, and (iii) the biofilm formed in the draw channel
      impacts the process performance more than when formed in the feed channel. The
      proposed mathematical model helps to understand the impact of biofouling in FO
      membrane systems and to develop possible strategies to reduce and control
      biofouling.

PMID- 27697689
TI  - Biogas production from hydrothermal liquefaction wastewater (HTLWW): Focusing on
      the microbial communities as revealed by high-throughput sequencing of full
      length 16S rRNA genes.
AB  - Hydrothermal liquefaction (HTL) is an emerging and promising technology for the
      conversion of wet biomass into bio-crude, however, little attention has been paid
      to the utilization of hydrothermal liquefaction wastewater (HTLWW) with high
      concentration of organics. The present study investigated biogas production from
      wastewater obtained from HTL of straw for bio-crude production, with focuses on
      the analysis of the microbial communities and characterization of the organics.
      Batch experiments showed the methane yield of HTLWW (R-HTLWW) was 184 mL/g COD,
      while HTLWW after petroleum ether extraction (PE-HTLWW), to extract additional
      bio-crude, had higher methane yield (235 mL/g COD) due to the extraction of
      recalcitrant organic compounds. Sequential batch experiments further demonstrated
      the higher methane yield of PE-HTLWW. LC-TOF-MS, HPLC and gel filtration
      chromatography showed organics with molecular weight (MW) < 1000 were well
      degraded. Results from the high-throughput sequencing of full-length 16S rRNA
      genes analysis showed similar microbial community compositions were obtained for
      the reactors fed with either R-HTLWW or PE-HTLWW. The degradation of fatty acids
      were related with Mesotoga infera, Syntrophomonas wolfei et al. by species level
      identification. However, the species related to the degradation of other
      compounds (e.g. phenols) were not found, which could be due to the presence of
      uncharacterized microorganisms. It was also found previously proposed criteria
      (97% and 98.65% similarity) for species identification of 16S rRNA genes were not
      suitable for a fraction of 16S rRNA genes.

PMID- 27697690
TI  - New oral cut-off time limits in NSW.
AB  - Standard collection procedure for the investigation of allegations of penile -
      oral assault has traditionally been the oral swab. Review of both the literature
      and NSW forensic laboratory results from oral swabbing has highlighted the sub
      optimal nature of this method for the recovery of both sperm and offender DNA.
      554 oral swabs, collected in NSW from 2010 to 2015, were analysed. Sperm
      detection occurred in only 4.2%. In the same period there was analysis of 104
      oral rinses (of which 16.4% were positive for sperm) and 71 peri-oral samples (of
      which 18.3% were positive for sperm). As a result, a decision was made to revise
      forensic collection guidelines for sample collection in cases of penile - oral
      assault. Oral swabbing is no longer recommended. Current NSW forensic collection
      guidelines recommend the collection of both an oral rinse and a peri-oral (lip)
      swab. Samples are to be taken in the first 12 h after a penile - oral assault in
      all cases where there is a suspicion of oral assault. Oral collections may be
      extended to 24 h post penile - oral assault in those cases where there is either
      a clear recollection of ejaculation into the mouth (or ejaculation elsewhere
      prior to penile penetration of the mouth) or in those cases where a complainant
      is clear that there had been penile penetration of the mouth but is unable to
      recall whether or not ejaculation has taken place.

PMID- 27697691
TI  - Reliability of physical examination tests for the diagnosis of knee disorders:
      Evidence from a systematic review.
AB  - Clinicians often rely on physical examination tests to guide them in the
      diagnostic process of knee disorders. However, reliability of these tests is
      often overlooked and may influence the consistency of results and overall
      diagnostic validity. Therefore, the objective of this study was to systematically
      review evidence on the reliability of physical examination tests for the
      diagnosis of knee disorders. A structured literature search was conducted in
      databases up to January 2016. Included studies needed to report reliability
      measures of at least one physical test for any knee disorder. Methodological
      quality was evaluated using the QAREL checklist. A qualitative synthesis of the
      evidence was performed. Thirty-three studies were included with a mean QAREL
      score of 5.5 +/- 0.5. Based on low to moderate quality evidence, the Thessaly
      test for meniscal injuries reached moderate inter-rater reliability (k = 0.54).
      Based on moderate to excellent quality evidence, the Lachman for anterior
      cruciate ligament injuries reached moderate to excellent inter-rater reliability
      (k = 0.42 to 0.81). Based on low to moderate quality evidence, the Tibiofemoral
      Crepitus, Joint Line and Patellofemoral Pain/Tenderness, Bony Enlargement and
      Joint Pain on Movement tests for knee osteoarthritis reached fair to excellent
      inter-rater reliability (k = 0.29 to 0.93). Based on low to moderate quality
      evidence, the Lateral Glide, Lateral Tilt, Lateral Pull and Quality of Movement
      tests for patellofemoral pain reached moderate to good inter-rater reliability (k
      = 0.49 to 0.73). Many physical tests appear to reach good inter-rater
      reliability, but this is based on low-quality and conflicting evidence. High
      quality research is required to evaluate the reliability of knee physical
      examination tests.

PMID- 27697692
TI  - Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia induce
      cell death and release of endogenous danger signals.
AB  - OBJECTIVE: The aim of this study was to analyze whether periodontopathogens
      induced inflammatory cell death and the release of diverse endogenous danger
      molecules in THP-1-derived macrophages. METHODS: The macrophages were treated
      with Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia.
      Activation of caspase-1 and caspase-4 was detected by Western blotting. Cell
      death of bacteria-stimulated macrophages was examined using a lactate
      dehydrogenase (LDH) assay and propidium iodide (PI)/annexin V (AV) staining.
      Levels of endogenous danger signals, including adenosine triphosphate (ATP), uric
      acid, heat shock protein 60 (HSP60), high-mobility group box protein 1 (HMGB1),
      and fibronectin in the culture supernatants were determined using an ATP
      bioluminescence assay kit, a uric acid assay kit, and Western blotting,
      respectively. RESULTS: T. denticola, P. gingivalis, and T. forsythia induced
      activation of caspase-1 and caspase-4. The LDH assay and PI/AV staining showed
      that all three pathogens induced pyroptotic cell death. All three bacteria
      induced release of ATP, which is an important ligand for inflammasome activation;
      the increase in ATP ultimately leads to caspase-1 activation. T. denticola
      induced release of HSP60 and fibronectin, while T. forsythia induced release of
      HMGB1 in addition to HSP60 and fibronectin. None of the endogenous molecules
      except for fibronectin were detected in P. gingivalis-infected cells, possibly
      due to degradation of these factors by the proteolytic activity of the bacteria.
      Interestingly, P. gingivalis induced uric acid release. CONCLUSION: Inflammatory
      cell death and endogenous danger molecules released from cells infected with
      periodontopathogens may play critical roles in the pathogenesis and progression
      of periodontitis by augmenting immune and inflammatory responses.

PMID- 27697693
TI  - Changes in the oral ecosystem induced by the use of 8% arginine toothpaste.
AB  - OBJECTIVE: Bacterial metabolism of arginine in the oral cavity has a pH-raising
      and thus, potential anti-caries effect. However, the influence of arginine on the
      oral microbial ecosystem remains largely unresolved. DESIGN: In this pilot study,
      nine healthy individuals used toothpaste containing 8% arginine for eight weeks.
      Saliva was collected to determine arginolytic potential and sucrose metabolic
      activity at the Baseline, Week 4, Week 8 and after a two weeks Wash-out period.
      To follow the effects on microbial ecology, 16S rDNA sequencing on saliva and
      plaque samples at Baseline and Week 8 and metagenome sequencing on selected
      saliva samples of the same time-points was performed. RESULTS: During the study
      period, the arginolytic potential of saliva increased, while the sucrose
      metabolism in saliva decreased. These effects were reversed during the Wash-out
      period. Although a few operational taxonomic units (OTUs) in plaque changed in
      abundance during the study period, there was no real shift in the plaque
      microbiome. In the saliva microbiome there was a significant compositional shift,
      specifically the genus Veillonella had increased significantly in abundance at
      Week 8. CONCLUSION: Indeed, the presence of arginine in toothpaste affects the
      arginolytic capacity of saliva and reduces its sucrose metabolic activity.
      Additionally, it leads to a shift in the salivary microbiome composition towards
      a healthy ecology from a caries point of view. Therefore, arginine can be
      regarded as a genuine oral prebiotic.

PMID- 27697695
TI  - Radical treatment of extensive nevoid hyperkeratosis of the areola and breast
      with surgical excision after mild response to topical agents: A case report.
AB  - INTRODUCTION: Nevoid hyperkeratosis of the nipple and/or areola (NHNA) is a
      benign lesion with a female predominance and an aesthetically disturbing
      appearance. Spontaneous remission is not reported and medical treatments proposed
      so far have shown variable results. PRESENTATION OF CASE: We describe a rare case
      of an extensive variant of NHNA covering almost the entire breasts' surface. At
      present, only three other reports are present in the literature. Medical
      treatment proved not completely effective and the patient was also affected by a
      significant breast asymmetry-hypertrophy. Therefore, NHNA was managed surgically
      with excision of the areolar affected portions while performing breast reduction
      lift. The result was satisfactory and without recurrence of lesions at 5-year
      follow-up. DISCUSSION: This case reported favorable outcomes of surgery for NHNA.
      Reports of success with these procedures are still limited, but the promising
      results in terms of radicality and aesthetic outcome suggest it should be offered
      to patients as a viable therapeutic option. CONCLUSION: Indications for surgical
      treatment of NHNA can be: unsatisfying response to topical agents; young patients
      who want to restore the aesthetic appearance of the breast; and patients with
      concomitant indication for corrective surgery of the breast. Advantages are:
      predictable time of healing; predictable final result; radical excision of the
      affected tissue; and possibility of histologic analysis of the whole areola. In
      rare cases of lesions extending to the breast, preliminary treatment with topical
      agents can limit the extent of excision. Management and treatment should always
      be tailor-made for each individual case.

PMID- 27697696
TI  - Basal cell carcinoma mimicking pilonidal sinus: A case report with literature
      review.
AB  - INTRODUCTION: Pilonidal sinus is a common benign disease that accounts for almost
      15% of anal suppurations while basal cell carcinoma is the most common malignancy
      of the sun-exposed area occurring mainly on the head and neck. We report a case
      of basal cell carcinoma presented with signs and symptoms of PNS. A 40-year-old
      male presented with swelling of the lower back for 2 years. On examination, there
      was a round, mobile, soft 4*2.5cm mass on the sacrococcygeal area. Ultrasound
      showed subcutaneous cystic lesion. Clinical diagnosis of PNS was done and
      excisional biopsy was performed under local anesthesia. The result of the
      histopathological examination was suggestive for basal cell carcinoma.
      CONCLUSION: Basal cell carcinoma should not be forgotten in differential
      diagnosis of superficial mass and abscesses.

PMID- 27697694
TI  - Regional expression of the MAPT gene is associated with loss of hubs in brain
      networks and cognitive impairment in Parkinson disease and progressive
      supranuclear palsy.
AB  - Abnormalities of tau protein are central to the pathogenesis of progressive
      supranuclear palsy, whereas haplotype variation of the tau gene MAPT influences
      the risk of Parkinson disease and Parkinson's disease dementia. We assessed
      whether regional MAPT expression might be associated with selective vulnerability
      of global brain networks to neurodegenerative pathology. Using task-free
      functional magnetic resonance imaging in progressive supranuclear palsy,
      Parkinson disease, and healthy subjects (n = 128), we examined functional brain
      networks and measured the connection strength between 471 gray matter regions. We
      obtained MAPT and SNCA microarray expression data in healthy subjects from the
      Allen brain atlas. Regional connectivity varied according to the normal
      expression of MAPT. The regional expression of MAPT correlated with the
      proportionate loss of regional connectivity in Parkinson's disease. Executive
      cognition was impaired in proportion to the loss of hub connectivity. These
      effects were not seen with SNCA, suggesting that alpha-synuclein pathology is not
      mediated through global network properties. The results establish a link between
      regional MAPT expression and selective vulnerability of functional brain networks
      to neurodegeneration.

PMID- 27697697
TI  - Corrigendum to "Concordance between DSM-5 and DSM-IV nicotine, alcohol, and
      cannabis use disorder diagnoses among pediatric patients" [Drug Alcohol Depend.
      140 (2014) 213-216].

PMID- 27697699
TI  - The effect of narrow provider networks on health care use.
AB  - Network design is an often overlooked aspect of health insurance contracts.
      Recent policy factors have resulted in narrower provider networks. We provide
      plausibly causal evidence on the effect of narrow network plans offered by a
      large national health insurance carrier in a major metropolitan market. Our
      econometric design exploits the fact that some firms offer a narrow network plan
      to their employees and some do not. Our results show that narrow network health
      plans lead to reductions in health care utilization and spending. We find
      evidence that narrow networks save money by selecting lower cost providers into
      the network.

PMID- 27697698
TI  - Characterization of brevetoxin (PbTx-3) exposure in neurons of the anoxia
      tolerant freshwater turtle (Trachemys scripta).
AB  - Harmful algal blooms are increasing in frequency and extent worldwide and occur
      nearly annually off the west coast of Florida where they affect both humans and
      wildlife. The dinoflagellate Karenia brevis is a key organism in Florida red
      tides that produces a suite of potent neurotoxins collectively referred to as the
      brevetoxins (PbTx). Brevetoxins bind to and open voltage gated sodium channels
      (VGSC), increasing cell permeability in excitable cells and depolarizing nerve
      and muscle tissue. Exposed animals may thus show muscular and neurological
      symptoms including head bobbing, muscle twitching, paralysis, and coma; large
      HABs can result in significant morbidity and mortality of marine life, including
      fish, birds, marine mammals, and sea turtles. Brevetoxicosis however is difficult
      to treat in endangered sea turtles as the physiological impacts have not been
      investigated and the magnitude and duration of brevetoxin exposure are generally
      unknown. In this study we used the freshwater turtle Trachemys scripta as a model
      organism to investigate the effects of the specific brevetoxin PbTx-3 in the
      turtle brain. Primary turtle neuronal cell cultures were exposed to a range of
      PbTx-3 concentrations to determine excitotoxicity. Agonists and antagonists of
      voltage-gated sodium channels and downstream targets were utilized to confirm the
      toxin's mode of action. We found that turtle neurons are highly resistant to PbTx
      3; while cell viability decreased in a dose dependent manner across PbTx-3
      concentrations of 100-2000nM, the EC50 was significantly higher than has been
      reported in mammalian neurons. PbTx-3 exposure resulted in significant Ca2+
      influx, which could be fully abrogated by the VGSC antagonist tetrodotoxin, NMDA
      receptor blocker MK-801, and tetanus toxin, indicating that the mode of action in
      turtle neurons is the same as in mammalian cells. As both turtle and mammalian
      VGSCs have a high affinity for PbTx-3, we suggest that the high resistance of the
      turtle neuron to PbTx-3 may be related to its ability to withstand anoxic
      depolarization. The ultimate goal of this work is to design treatment protocols
      for sea turtles exposed to red tides worldwide.

PMID- 27697700
TI  - Mechanistic insights into Diels-Alder reactions in natural product biosynthesis.
AB  - Natural enzymes that catalyze Diels-Alder reactions have long been sought after,
      yet few enzymes have been experimentally confirmed to perform this reaction. In
      the past five years, several stand-alone enzymes that can catalyze the Diels
      Alder reaction had been identified and characterized. Among which, the crystal
      structures of SpnF, PyrI4 and AbyU have been determined. The structures of PyrI4
      and AbyU, which are involved in spirotetronate/spirotetramate biosynthesis, are
      particularly informative since they shed light on how a natural catalyst captures
      the flexible substrate and facilitates the intramolecular Diels-Alder reaction
      through stabilization of the transition state in catalysis. These pioneering
      studies will inspire the design of artificial catalysts for Diels-Alder
      reactions.

PMID- 27697701
TI  - Non-natural carbenoid and nitrenoid insertion reactions catalyzed by heme
      proteins.
AB  - Despite increasing interest in using enzymes as tools for synthesis, many
      reactions discovered through the creativity of synthetic chemists remain beyond
      the scope of biocatalysis. This vacancy in the field has compelled researchers to
      develop strategies to adapt protein scaffolds for new reactivity. Heme proteins
      have recently been shown to activate synthetic precursors to generate reactive
      metallocarbenoid and metallonitrenoid species that enable the biosynthetic
      construction of novel C-C, C-N, and other bonds using mechanisms not previously
      explored by Nature. By interrogating heme proteins with synthetic, non-natural
      reagents, scientists are merging the reaction space traditionally dominated by
      organocatalysis and transition metal catalysis with the mild reaction conditions,
      selectivity, and adaptability imparted by native protein scaffolds.

PMID- 27697702
TI  - Abnormal regulation of the antiviral response in neurological/neurodegenerative
      diseases.
AB  - Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic
      lateral sclerosis are a few examples of debilitating
      neurological/neurodegenerative diseases for which there are currently no curative
      treatments. Recent evidence has strongly suggested a role for neuroinflammation
      in both the onset and progression of these diseases. However, the mechanisms that
      initiate neuroinflammation are presently unclear. Mounting evidence suggests that
      environmental factors are likely involved. One proposed mechanism linking both
      genetic and environmental factors is dysregulation of the antiviral response.
      Indeed, many mutations that have been linked to neurological conditions occur in
      genes related to the antiviral response. Although the products of these genes may
      have potent antiviral activities - they can also have deleterious effects when
      their expression is not appropriately regulated. For that reason, expression of
      antiviral genes is a tightly controlled process. Herein, we review the various
      antiviral genes that have been linked to neurological conditions. We focus
      specifically on type I interferonopathies, the symptoms of which are often
      evident at birth, and neurodegenerative diseases, which frequently onset later in
      life.

PMID- 27697703
TI  - Dynamics of cytokine mRNA expression and fecal biomarkers in school-children
      undergoing a double-blind placebo-controlled food challenge series.
AB  - BACKGROUND: There is need for prognostic markers for symptomatic food allergy
      since current diagnostic methods are insufficient and/or time and labor
      consuming. OBJECTIVE: To estimate the cytokine mRNA profiles in peripheral blood
      mononuclear cells (PBMC) before and after a double-blind placebo-controlled food
      challenge series in schoolchildren with suspected allergy to milk, egg or cod and
      in healthy controls. Analyses of fecal inflammatory biomarkers before and after
      the challenge were included. METHODS: Twelve-year-old children from a population
      based cohort reporting complete avoidance of milk, egg, cod or wheat due to
      perceived hypersensitivity were clinically examined and those with suspected food
      allergy were evaluated with a 3-session double-blind placebo-controlled food
      challenge (n=18). Seven healthy controls participated in a double-blind challenge
      with egg. Before and after the challenge series, the cytokine mRNA expression was
      quantified for 13 cytokines discriminating between humoral Th2-, cytotoxic Th1-,
      regulatory Th3/Tr1- and inflammatory responses. Fecal calprotectin and eosinophil
      derived neurotoxin (EDN) were also analyzed in children with suspected food
      allergy before and after the challenge series. RESULTS: Pre challenge, children
      with suspected food allergy had higher IL-13andTNF-alpha expression and lower IFN
      gamma and IL-15 expression compared to healthy controls (all p<0.05). Children
      with challenge-proven food allergy had increased IL13andIL-10 expression compared
      to the levels seen in negative challenges (p<0.05). Post challenge, IL-1beta and
      IL-6 mRNA levels were elevated in the food allergic children compared to controls
      (p<0.05). Fecal calprotectin and EDN levels were higher in challenge-proven food
      allergy compared to a negative challenge although not statistically
      significantly. CONCLUSION & CLINICAL RELEVANCE: Increased baseline mRNA levels of
      the Th2-related cytokine IL-13 and the regulatory cytokine IL-10 predicted a
      positive food challenge outcome. These cytokines in combination with fecal
      calprotectin and EDN might serve as future prognostic markers for symptomatic,
      IgE-mediated food allergy but need further validation in a larger patient cohort.

PMID- 27697704
TI  - Mercury and selenium in the food web of Lake Nahuel Huapi, Patagonia, Argentina.
AB  - Despite located far from point sources of Hg pollution, high concentrations were
      recorded in plankton from the deep oligotrophic Lake Nahuel Huapi, located in
      North Patagonia. Native and introduced top predator fish with differing feeding
      habits are a valuable economic resource to the region. Hence, Hg and Se trophic
      interactions and pathways to these fish were assessed in the food web of this
      lake at three sites, using stable nitrogen and carbon isotopes. As expected based
      on the high THg in plankton, mercury did not biomagnify in the food web of Lake
      Nahuel Huapi, as most of the THg in plankton is in the inorganic form. As was
      observed in other aquatic systems, Se did not biomagnify either. When trophic
      pathways to top predator fish were analyzed, they showed that THg biomagnified in
      the food chains of native fish but biodiluted in the food chains of introduced
      salmonids. A more benthic diet, typical of native fish, resulted in higher [THg]
      bioaccumulation than a more pelagic or mixed diet, as in the case of introduced
      fish. Se:THg molar ratios were higher than 1 in all the fish species, indicating
      that Se might be offering a natural protection against Hg toxicity.

PMID- 27697706
TI  - Electro-oxidation and characterization of nickel foam electrode for removing
      boron.
AB  - The electrocoagulation (EC) using metallic Ni foam as electrodes was studied for
      the removal of boron from solution. The electrolytic parameters were pH (4-12),
      current density (0.6-2.5 mA cm-2), and initial concentration of boron (10-100 mg
      L-1). Experimental results revealed that removal efficiency was maximized at pH 8
      9, and decreased as the pH increased beyond that range. At particular onset
      potentials (0.5-0.8 V vs. Hg/HgO), the micro-granular nickel oxide that was
      created on the surface of the nickel metal substrate depended on pH, as
      determined by cyclic voltammetry. Most of the crystallites of the precipitates
      comprised a mixed phase of beta-Ni(OH)2, a theophrastite phase, and NiOOH, as
      revealed by XRD and SEM analyses. A current density of 1.25 mA cm-2 was effective
      in the EC of boron, and increasing the concentration of boric acid from 10 to 100
      mg L-1 did not greatly impair removal efficiency. A kinetic investigation
      revealed that the reaction followed a pseudo-second order rate model. The optimal
      conditions under which 99.2% of boron was removed from treated wastewater with 10
      mg L-1-B, leaving less than 0.1 mg L-1-B in the electrolyte, were pH 8 and 1.25
      mA cm-2 for 120 min.

PMID- 27697705
TI  - Pentachlorophenol affected both reproductive and interrenal systems: In silico
      and in vivo evidence.
AB  - The present study investigated the effects on reproductive and interrenal system
      by pentachlorophenol (PCP) using in silico and in vivo assays. Molecular docking
      results indicated interacting potency of PCP with steroid receptors (ERalpha,
      ERbeta, AR, GR) but not Cytochrome P450 enzymes (CYPs). In the in vivo assay,
      sexually matured rare minnow (Gobiocypris rarus) was exposed to environmental
      relevant concentrations of PCP (0, 0.5, 5, 50 MUg L-1). In male fish, 14-d
      exposure caused up-regulation of mRNA levels of hepatic eralpha, erbeta, ar, gr,
      vtg and gonadal eralpha, vtg, ar, dmrt1, providing evidence for agonistic
      activities for steroid receptors by PCP. The up-regulated mRNA of gnrh, crf, pomc
      in the brain also indicated feed-forward responses of the hypothalamic-pituitary
      gonadal/interrenal (HPG/I) axis. However, at 28th d the feed-forward response of
      the HPG axis seemed eased back and the HPI axis showed negative feedback
      responses. Corresponding changes including increases of plasma steroid hormones,
      inhibition of spermatogenesis, and decreased RSI were observed in male fish upon
      28-d exposure to PCP. In the females, a transition from feed-forward responses to
      negative feedbacks of the HPG/I axis was also indicated by the transcriptional
      profiles at 14th and 28th day. Corresponding changes including increased E2, T
      and decreased C levels, degenerated ovaries, and decreased GSI and RSI were also
      observed. Overall, we concluded that PCP could interfere with steroid receptors,
      evoke responses of HPG/I axis, and finally result in adverse effects on
      reproductive and interrenal system in rare minnow at environmental relevant
      concentrations.

PMID- 27697707
TI  - Exploring the ability of cations to facilitate binding between inorganic
      oxyanions and humic acid.
AB  - The mobility and fate of inorganic oxyanions in the environment can be greatly
      influenced by interactions with natural organic matter (NOM). There is increasing
      evidence that this interaction between two anionic species is facilitated by
      cationic bridges, but detailed mechanistic studies into this system are
      challenging due to the heterogeneous nature of NOM. This work examines the
      ability of cations (FeIII, CrIII, AlIII, or GaIII) to form ternary complexes with
      Suwannee River humic acid (SRHA) and the oxyanions of As (AsIII and AsV) and Se
      (SeIV and SeVI). Complexes were characterized by separating SRHA from unbound
      species using size exclusion chromatography coupled to ICP-MS to determine its
      metal content. Unlike CrIII and FeIII, the post-transition metal ions AlIII and
      GaIII proved ineffective at forming ternary complexes with any of the oxyanions,
      although minor complexation was observed with GaIII, suggesting that
      electrostatic interactions are not the primary driving force behind the
      stabilization of these ternary complexes. The results also show differences in
      the behavior of FeIII and CrIII that may indicate that the two cations stabilize
      the ternary complexes by different mechanisms.

PMID- 27697708
TI  - Chemical removal of nitrate from water by aluminum-iron alloys.
AB  - Zero-valent iron has been intensively investigated in chemical reduction of
      nitrate in water, but the reduction requires acidic or weak acidic pH conditions
      and the product of the reduction is exclusively ammonium, an even more toxic
      substance. Zero-valent aluminum is a stronger reductant than iron, but its use
      for the reduction of aqueous nitrate requires considerably alkaline pH
      conditions. In this study, aluminum-iron alloys with an iron content of 10%, 20%
      and 58% (termed Al-Fe10, Al-Fe20 and Al-Fe58, respectively) were investigated for
      the reduction of aqueous nitrate. Al-Fe alloys were efficient to reduce nitrate
      in water in an entire pH range of 2-12 and the reduction proceeded in a pseudo
      first order at near neutral pH conditions. The observed reaction rate constant
      (Kobs) of Al-Fe10 was 3 times higher than that of Fe and the Kobs of Al-Fe20
      doubled that of Al-Fe10. The nitrogen selectivity of the reduction by Al-Fe10, Al
      Fe20 and Al-Fe58 was 17.6%, 23.9% and 40.3%, respectively at pH 7 and the
      nitrogen selectivity by Al-Fe20 increased from 18.9% at pH 2-60.3% at pH 12. The
      enhanced selectivity and reactivity of Al-Fe alloys were likely due to the
      presence of an intermetallic Al-Fe compound (Al13Fe4).

PMID- 27697710
TI  - Immunotoxic effects of atrazine and its main metabolites at environmental
      relevant concentrations on larval zebrafish (Danio rerio).
AB  - Atrazine (ATZ) and its main metabolites, i.e., diaminochlorotriazine (DACT),
      deisopropylatrazine (DIP), and deethylatrazine (DE), have been widely detected in
      surface water around the world. In the present study, to determine their
      immunotoxic effects, zebrafish during the early developmental stage were exposed
      to ATZ and its main metabolites at environmental concentrations (30, 100, 300 MUg
      L-1). It was observed that ATZ, DACT, DIP and DE selectively induced the
      transcription of immunotoxic related genes including Tnfalpha, Il-1beta, Il-6, Il
      8, Cxcl-clc and Cc-chem in larval zebrafish. Pretreatment with ATZ and its
      metabolites also changed the immune response of larval zebrafish to LPS and E.
      coli challenge, which was indicated by the alternation in the mRNA levels of some
      cytokines. In addition, 300 MUg L-1 ATZ and DACT exposure could also increase the
      release of tryptase into water, indicating that they increased the anaphylactoid
      reaction in the larval zebrafish. According to these results, both of ATZ and its
      metabolites exposure could cause the immunotoxicity in larval zebrafish. Thus, we
      thought that the ecological risks of the metabolites of ATZ on aquatic organisms
      could not be ignored.

PMID- 27697709
TI  - Removal of copper, nickel and chromium mixtures from metal plating wastewater by
      adsorption with modified carbon foam.
AB  - In this study, the characterizations and adsorption efficiencies for chromium,
      copper and nickel were evaluated using manufacture-grade Fe2O3-carbon foam. SEM,
      XRD, XRF and BET analyses were performed to determine the characteristics of the
      material. Various pore sizes (12-420 MUm) and iron contents (3.62%) were found on
      the surface of the Fe2O3-carbon foam. Fe2O3-carbon foam was found to have
      excellent adsorption efficiency compared to carbon foam for mixed solutions of
      cationic and anionic heavy metals. The adsorption capacities for chromium, copper
      and nickel were 6.7, 3.8 and 6.4 mg/g, respectively, which were obtained using a
      dual exponential adsorption model. In experiments with varying dosages of the
      Fe2O3 powder, no notable differences were observed in the removal efficiency. In
      a fixed-bed column test, Fe2O3-carbon foam achieved adsorption capacities for
      chromium, copper and nickel of 33.0, 12.0 and 9.5 mg/g, respectively, after 104
      h. Based on these results, Fe2O3-carbon foam was observed to be a promising
      material for treatment of plating wastewater.

PMID- 27697711
TI  - The effect of low levels of lead (Pb) in the blood on levels of sphingosine-1
      phosphate (S1P) and expression of S1P receptor 1 in the brain of the rat in the
      perinatal period.
AB  - Sphingolipids are the main components of the lipid membrane. They also perform
      structural functions and participate in many signal transmission processes. One
      of the bioactive sphingolipids is sphingosine-1-phosphate (S1P), a ligand for
      five G protein-coupled receptors (S1PRs1-5), which can also act as an
      intracellular second messenger. S1P is responsible for the stimulation of
      progenitor cells in the brain, but it can also induce apoptosis of mature
      neurons. This study is aimed at assessing the effect of pre- and neonatal
      exposure to permissible Pb concentrations on S1P levels and S1PR1 (EDG1)
      expression in the prefrontal cortex, cerebellum, and hippocampus of rats. The
      concentrations of S1P were determined by RP-HPLC, S1PR1 expression was determined
      by RT PCR and Western Blot, and receptor immunolocalization was determined by
      immunohistochemistry method. Our results showed that even low blood Pb
      concentrations, i.e. within the acceptable limit of 10 MUg/dL caused changes in
      the concentration of S1P in the cerebellum, prefrontal cortex, and hippocampus.
      Our data also showed a significant decrease in the level of S1PR1 in all studied
      part of brain, without significant changes in S1PR1 gene expression. Pre- and
      neonatal exposure to Pb also resulted in a decrease in the expression of S1PR1 in
      glial cells in all regions of the Cornu Ammonis (CA1-CA4) and Dentate Gyrus in
      the hippocampus, as well as in all layers of the cerebellum and prefrontal
      cortex, compared to the unexposed control group.

PMID- 27697712
TI  - Degradation pathways of aniline in aqueous solutions during electro-oxidation
      with BDD electrodes and UV/H2O2 treatment.
AB  - In this work, it has been studied the mineralization of aniline, a toxic
      substance of low biodegradability typically found in many industrial wastewaters,
      through electro-oxidation using boron doped diamond (BDD) electrodes and photo
      oxidation (UV photolysis and UV/H2O2 treatments). It was observed that in electro
      oxidation and UV/H2O2, it was feasible to reach aniline mineralizations higher
      than 85%. Two different degradation routes have been observed during the aniline
      oxidation in these two treatments. The first route was the mineralization
      pathway, in which aniline was oxidized to CO2, water and nitrate. The second
      route was the polyaniline pathway in which polyanilines of high molecular weight
      are formed. The intermediate compounds involved in both degradation routes are
      different depending on the treatment used. In the electro-oxidation,
      denitrification processes were also observed. From an economical point of view,
      electro-oxidation of aniline using BDD electrodes is more interesting than
      UV/H2O2 due it has an 87% lower operational cost. So, electro-oxidation using BDD
      electrodes seems to be a more suitable technique for the mineralization of
      wastewater containing aniline than UV or H2O2 based technologies.

PMID- 27697713
TI  - Neurotoxicity induced by arsenic in Gallus Gallus: Regulation of oxidative stress
      and heat shock protein response.
AB  - Arsenic, a naturally occurring heavy metal pollutant, is one of the functioning
      risk factors for neurological toxicity in humans. However, little is known about
      the effects of arsenic on the nervous system of Gallus Gallus. To investigate
      whether arsenic induce neurotoxicity and influence the oxidative stress and heat
      shock proteins (Hsps) response in chickens, seventy-two 1-day-old male Hy-line
      chickens were treated with different doses of arsenic trioxide (As2O3). The
      histological changes, antioxidant enzyme activity, and the expressions of Hsps
      were detected. Results showed slightly histology changes were obvious in the
      brain tissues exposure to arsenic. The activities of Glutathione peroxidase (GSH
      Px) and catalase (CAT) were decreased compared to the control, whereas the
      malondialdehyde (MDA) content was increased gradually along with increase in diet
      arsenic. The mRNA levels of Hsps and protein expressions of Hsp60 and Hsp70 were
      up-regulated. These results suggested that sub-chronic exposure to arsenic
      induced neurotoxicity in chickens. Arsenic exposure disturbed the balance of
      oxidants and antioxidants. Increased heat shock response tried to protect chicken
      brain tissues from tissues damage caused by oxidative stress. The mechanisms of
      neurotoxicity induced by arsenic include oxidative stress and heat shock protein
      response in chicken brain tissues.

PMID- 27697714
TI  - Relationships between serum BDNF and the antidepressant effect of acute exercise
      in depressed women.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has recently emerged as one
      potential mechanism with which exercise improves mood in major depressive
      disorder (MDD). This study examined the relationship between changes in serum
      total BDNF and mood following acute exercise in MDD. It was hypothesized that
      acute exercise would increase BDNF in an intensity-dependent manner and that
      changes in BDNF would be significantly related to improvement in depressed mood
      post-exercise. METHODS: Twenty-four women (age: 38.6+/-14.0years) with MDD
      exercised for 30min on a stationary bicycle at light, moderate and hard exercise
      intensities and performed a quiet rest session using a within-subjects,
      randomized and counter-balanced design. Before, 10 and 30min after each session,
      participants completed the profile of mood states (POMS). Blood was drawn before
      and within 10min after completion of each session and serum total BDNF (sBDNF)
      was measured by enzyme-linked immunosorbent assay. Acute exercise-induced changes
      in POMS Depression and sBDNF were analyzed via 4 session (quiet rest, light,
      moderate, hard) by 2 measurement (pre, post) ANOVA. Secondary analyses examined
      the effects of baseline mood and antidepressant usage on sBDNF. RESULTS: Exercise
      resulted in an acute improvement in depressed mood that was not intensity
      dependent (p>0.05), resulting in significant acute increases in sBDNF (p=0.006)
      that were also not intensity-dependent (p>0.05). Acute changes in sBDNF were not
      significantly correlated to changes in POMS depression at 10m (r=-0.171, p=0.161)
      or 30m (r=-0.151, p=0.215) post-exercise. The fourteen participants taking
      antidepressant medications exhibited lower post-exercise sBDNF (p=0.015) than the
      participants not currently taking antidepressants, although mood responses were
      similar. CONCLUSION: Acute exercise is an effective mood-enhancing stimulus,
      although sBDNF does not appear to play a role in this short-term response.
      Patients who are not currently taking antidepressant medications and those who
      have greater pre-exercise depression may experience a greater sBDNF response to
      exercise, but the clinical significance of this is currently unclear. Circulating
      BDNF levels are unlikely to be altered by steady-state acute exercise in a linear
      dose-dependent manner. This does not eliminate its potential relevance in the
      antidepressant response to chronic exercise training, but suggests that other
      mechanisms are involved in the acute affective response to exercise in
      depression.

PMID- 27697715
TI  - Swelling of glucose-responsive gels functionalized with boronic acid.
AB  - A model is developed for the elastic response of a glucose-sensitive gel
      functionalized with boronic acid under swelling in aqueous solutions of glucose
      with various pH. A gel is treated as a three-phase medium composed of a solid
      phase (partially ionized polymer network), solvent (water), and solute (mobile
      glucose molecules and ions). Constitutive equations are derived by means of the
      free energy imbalance inequality for three-dimensional deformation with finite
      strains. Numerical analysis demonstrates the ability of the model to describe the
      effects of pH, molar fraction of glucose, and concentration of functional groups
      on equilibrium water uptake diagrams under unconstrained and constrained
      swelling.

PMID- 27697716
TI  - Effect of an amorphous titania nanotubes coating on the fatigue and corrosion
      behaviors of the biomedical Ti-6Al-4V and Ti-6Al-7Nb alloys.
AB  - An array of self-organized TiO2 nanotubes with an amorphous structure was
      produced on the biomedical Ti-6Al-4V and Ti-6Al-7Nb alloys, and the resulting
      fatigue and corrosion behaviors were studied. The electrochemical response of the
      nanotubular oxide surfaces was investigated in Ringer physiological solution
      through potentiodynamic polarization and electrochemical impedance spectroscopy
      measurements. The absence of transpassivation in the chloride-containing
      solution, in addition to the micron-scale values of the passivation current
      density, indicated the excellent corrosion behavior of the coating and the
      satisfactory protection against the creation of potential stress concentrators in
      the surface. Axial fatigue tests were performed in physiological solution on
      polished and coated conditions, with characterization of the treated surfaces by
      scanning electron microscopy before and after the tests. The surface modification
      was not deleterious to the fatigue response of both alloys mainly due to the nano
      scale dimension of the nanotubes layer. An estimation based on fracture mechanics
      revealed that a circumferential crack in the range of 5MUm depth would be
      necessary to affect the fatigue performance, which is far from the thickness of
      the studied coating, although no cracks were actually observed in the oxide
      surfaces after the tests.

PMID- 27697717
TI  - Gel-spinning of mimetic collagen and collagen/nano-carbon fibers: Understanding
      multi-scale influences on molecular ordering and fibril alignment.
AB  - Synthetic gel-spun collagen and collagen/nano-carbon fibers were found to exhibit
      structural mimicry comparable to native tendons. X-ray scattering and microscopy
      analyses are used to characterize the molecular and fibrillar alignment in the
      synthetic fibers, where D-banding is observed throughout the spun fibers -
      consistent with native collagen. For the composite collagen/nano-carbon fibers,
      the morphology and dispersion quality of the nano-carbons within was found to
      play a significant role in influencing collagen molecular ordering and fibril
      alignment. Fibrillar and molecular alignment was also better preserved during
      elongation of the composites as compared to the control collagen fibers. These
      results show the structural influence of a rigid inclusion on the collagen fibril
      structure. Both dry- and wet-state tensile testing were performed on the collagen
      fibers, and these results show behavior comparable to the native materials. Dry
      state tests also reveal interfacial interaction between the nano-fillers and the
      collagen fibrils through theoretical analysis. Wet-state tensile testing
      indicates the structure-property behavior of the mimetic hierarchical structure
      within the synthetic fibers.

PMID- 27697718
TI  - Outcome of temporal lobe epilepsy surgery evaluated with bitemporal intracranial
      electrode recordings.
AB  - BACKGROUND: Temporal lobe epilepsy (TLE) with unclear lateralization may require
      intracranial implantation of electrodes (IIE). We retrospectively assessed the
      association between the use of IIE and long-term outcomes in patients undergoing
      anterior temporal lobectomy (ATL). PARTICIPANTS AND METHODS: We retrospectively
      reviewed the records of 1,032 patients undergoing epilepsy surgery at our center
      from 1977 to 2006. Patients who underwent ATL were included. Seizure outcome was
      assessed through final follow-up. Those who underwent scalp and IIE (mostly
      evaluated with temporal subdural strip electrodes) were compared. RESULTS: From
      497 patients who underwent ATL, 139 did so after IIE placement in the temporal
      lobes. Mean age at surgery was 32.3+/-12.3years and median duration of follow-up
      24 months (range: 6-36). Fifty-three percent of those evaluated with IIE were
      seizure-free at their last available visit (vs. 68% evaluated with only scalp
      EEG, p=0.002). Patients with lesional TLE generally had a better outcome (65.5%
      seizure free) than those without lesions (56.3%, p=0.093), especially for
      unilateral TLE diagnosed with IIE. In a multivariate Cox regression analyses
      adjusted for gender, neuropsychological concordance, pathological findings, and
      post-operative seizures, bilateral TLE predicted seizure recurrence in IIE
      patients (HR=2.08, 95% CI: 1.08-4.0, p=0.029). CONCLUSIONS: More than a half of
      those who undergo IIE in suspected TLE are seizure free after ATL. IIE allows for
      the identification of surgical candidates.

PMID- 27697719
TI  - Medial-lateral centre of mass displacement and base of support are equally good
      predictors of metabolic cost in amputee walking.
AB  - Amputees are known to walk with greater metabolic cost than able-bodied
      individuals and establishing predictors of metabolic cost from kinematic
      measures, such as centre of mass (CoM) motion, during walking are important from
      a rehabilitative perspective, as they can provide quantifiable measures to target
      during gait rehabilitation in amputees. While it is known that vertical CoM
      motion poorly predicts metabolic cost, CoM motion in the medial-lateral (ML) and
      anterior-posterior directions have not been investigated in the context of gait
      efficiency in the amputee population. Therefore, the aims of this study were to
      investigate the relationship between CoM motion in all three directions of
      motion, base of support and walking speed, and the metabolic cost of walking in
      both able-bodied individuals and different levels of lower limb amputee. 37
      individuals were recruited to form groups of controls, unilateral above- and
      below-knee, and bilateral above-knee amputees respectively. Full-body optical
      motion and oxygen consumption data were collected during walking at a self
      selected speed. CoM position was taken as the mass-weighted average of all body
      segments and compared to each individual's net non-dimensional metabolic cost.
      Base of support and ML CoM displacement were the strongest correlates to
      metabolic cost and the positive correlations suggest increased ML CoM
      displacement or Base of support will reduce walking efficiency. Rehabilitation
      protocols which indirectly reduce these indicators, rather than vertical CoM
      displacement will likely show improvements in amputee walking efficiency.

PMID- 27697720
TI  - Tuning the constrained photophysics of a pyrazoline dye 3-naphthyl-1-phenyl-5-(4
      carboxyphenyl)-2-pyrazoline inside the cyclodextrin nanocavities: A detailed
      insight via experimental and theoretical approach.
AB  - The modulation in the photophysics of a pyrazoline dye 3-naphthyl-1-phenyl-5-(4
      carboxyphenyl)-2-pyrazoline (NPCP), when it drifts from bulk water into the
      nanocages of aqueous cyclodextrin solutions was investigated. The intramolecular
      charge transfer (ICT) fluorescence band intensity was found to increase with a
      blue shift in the presence of cyclodextrins. The results from 1H NMR and 1HH COSY
      NMR spectral analysis clearly points out the position of pyrazoline ring inside
      the cavity and its role in complexation process. A quantitative assessment of the
      emission intensity data on Benesi-Hildebrand (B-H) equation along with ESI-MS
      spectra reveals the probable stoichiometry of NPCP-CD complexes. Molecular
      docking and molecular dynamics studies were conducted for beta/gamma cyclodextrin
      associated inclusion complexes of NPCP. The results obtained by computational
      studies are in good relation with the data obtained through experimental methods
      and both ascertain the encapsulation of NPCP into cyclodextrins.

PMID- 27697721
TI  - Characterization and intramolecular bonding patterns of busulfan: Experimental
      and quantum chemical approach.
AB  - The investigations of structural conformers, molecular interactions and
      vibrational characterization of pharmaceutical drug are helpful to understand
      their behaviour. In the present work, the 2D potential energy surface (PES) scan
      has been performed on the dihedral angles C6O4S1C5 and C25S22O19C16 to find the
      stable conformers of busulfan. In order to show the effects of long range
      interactions, the structures on the global minima of PES scan have been further
      optimized by B3LYP/6-311++G(d,p) method with and without empirical dispersion
      functional in Gaussian 09W package. The presence of n->sigma* and sigma->sigma*
      interactions which lead to stability of the molecule have been predicted by
      natural bond orbital analysis. The strong and weak hydrogen bonds between the
      functional groups of busulfan were analyzed using quantum topological atoms in
      molecules analysis. In order to study the long-range forces, such as van der
      Waals interactions, steric effect in busulfan, the reduced density gradient as
      well as isosurface defining these interactions has been plotted using Multiwfn
      software. The spectroscopic characterization on the solid phase of busulfan has
      been studied by experimental FT-IR and FT-Raman spectra. From the 13C and 1H NMR
      spectra, the chemical shifts of individual C and H atoms of busulfan have been
      predicted. The maximum absorption wavelengths corresponding to the electronic
      transitions between the highest occupied molecular orbital and the lowest
      unoccupied molecular orbital of busulfan have been found by UV-vis spectrum.

PMID- 27697722
TI  - Determination of deferasirox in human plasma by short-end injection and sweeping
      with a field-amplified sample stacking and micellar electrokinetic
      chromatography.
AB  - A field-amplified sample stacking-sweeping micellar electrokinetic chromatography
      with short-end injection was established for determination of deferasirox (DFX)
      in plasma. DFX was extracted from plasma and reconstituted with deionized water
      (lower conductivity solution). Capillary (effective length, 10cm) was filled with
      background electrolyte (40mM phosphate buffer, pH 4.5, containing 20% methanol).
      After sample loading from outlet end at 5psi for 15s, separation was carried out
      by applying high voltage at 15kV for 10min. Sodium dodecyl sulfate (SDS) was used
      to sweep DFX for enhancing sensitivity. The optimal CE separation conditions were
      40mM phosphate buffer at pH 4.5 containing 100mM SDS and 20% methanol. The
      analysis time was about 3.5min for DFX. The calibration curve of DFX was ranged
      from 1 to 20MUg/ml. The linearity (r) was more than 0.998. RSD and RE in intra-
      and inter-day assays were all below 12.14%. The limit of detection (LOD, S/N=3)
      for DFX was 0.3MUg/ml. The sensitivity enhancement factor between sweeping-FASS
      MEKC and capillary zone electrophoresis is 3.3. Finally, the method was applied
      for determination of DFX in beta-thalassemia patients.

PMID- 27697723
TI  - Anticancer effect of SZC015 on lung cancer cells through ROS-dependent apoptosis
      and autophagy induction mechanisms in vitro.
AB  - Oleanolic acid (OA) and its several derivatives possess various pharmacological
      activities, such as antitumor and anti-inflammation. In present study, anticancer
      effect of SZC015, an OA derivative, and its underlying mechanisms were
      investigated. We demonstrated that cell viability was significantly decreased in
      SZC015-treated lung cancer cells, but has less cytotoxicity in human bronchial
      epithelial cell line. Further investigation verified that apoptosis and autophagy
      induction and G0/G1 phase arrest were observed in SZC015-treated H322 cells.
      Mechanically, the level of Akt, p-Akt, p-IkappaBalpha, and total p65, the p-p65
      in the cytoplasm and nucleus were suppressed by SZC015 in H322 cells,
      respectively. Inhibition of p65 nuclear translocation was also confirmed by
      immunofluorescence staining. In addition, co-treatment with chloroquine, an
      autophagy inhibitor, significantly inhibited SZC015-induced autophagy and
      enhanced SZC015-induced apoptotic cell death. Intracellular ROS was increased in
      a concentration-dependent manner, which could be prevented by N-Acetyl l
      Cysteine, an ROS scavenger. Moreover, the level of Akt and procaspase-3 were
      increased, while the ratio of LC3 II/I was decreased. Taken together, our study
      demonstrates that the inhibitory effect of SZC015 against H322 cells is mediated
      by excessive ROS generation that could suppress Akt/NF-kappaB signaling pathway,
      which thereby leads to apoptotic and autophagic cell death.

PMID- 27697724
TI  - Suppressive effect of beta,beta-dimethylacryloyl alkannin on activated dendritic
      cells in psoriasis by the TLR7/8 pathway.
AB  - beta,beta-dimethylacryloyl alkannin (DMA) is a key component of Lithospermum and
      possesses good efficacy for treating psoriasis. DMA inhibits activated dendritic
      cells (DCs), but the mechanism is unknown. Therefore, this study aimed to explore
      the modulation of the TLR7/8 pathway by DMA in psoriasis-activated DCs. Models of
      psoriasis-like skin lesions were established using BALB/c mice; 8 mice were
      treated with DMA (2.5mg/kg). Bone marrow cells were isolated and induced into DCs
      using R848, a TLR7/8 agonist. Splenic CD11c+ cells were detected by flow
      cytometry. Skin CD11c+ cells were detected by immunofluorescence. TLR7, TLR8,
      MYD88, and IRAKM proteins were detected by Western blot. The effects of DMA on
      surface molecules of DCs were observed by flow cytometry. mRNA expression of
      inflammatory factors was detected by qRT-PCR. Secreted cytokines were detected by
      cytometric bead array. Compared with the model group, psoriasis-like skin lesions
      were alleviated by DMA, the splenic CD11c+ cells were significantly decreased
      (P<0.01), and CD11c+ cell numbers in skin lesions were decreased (P<0.01).
      Expression levels of TLR7, MYD88, and IRAKM were significantly decreased
      (P<0.05). R848-stimulated DCs showed increased expression of I-A/I-E, CD80, and
      CD86 (P<0.01), increased IL-23 and IL-1beta mRNA and secretion (P<0.05), and
      increased TLR7, TLR8, MYD88, and IRAKM expression (P<0.01); DMA inhibited all of
      these effects of the TLR7/8 pathway activation by R848 (P<0.05). In conclusion,
      DMA could inhibit psoriasis-activated DCs via the TLR7/8 pathway.

PMID- 27697725
TI  - Effects of beta-tricalcium phosphate particles on primary cultured murine
      dendritic cells and macrophages.
AB  - Beta-tricalcium phosphate (beta-TCP) is widely used for bone substitution in
      clinical practice. Particles of calcium phosphate ceramics including beta-TCP act
      as an inflammation mediators, which is an unfavorable characteristic for a bone
      substituent or a prosthetic coating material. It is thought that the stimulatory
      effect of beta-TCP on the immune system could be utilized as an immunomodulator.
      Here, in vitro effects of beta-TCP on primary cultured murine dendritic cells
      (DCs) and macrophages were investigated. beta-TCP particles enhanced expression
      of costimulatory surface molecules, including CD86, CD80, and CD40 in DCs, CD86
      in macrophages, and MHC class II and class I molecules in DCs. DEC205 and CCR7
      were up-regulated in beta-TCP-treated DCs. Production of cytokines and
      chemokines, including CCL2, CCL3, CXCL2, and M-CSF, significantly increased in
      DCs; CCL2, CCL3, CCL4, CCL5, CXCL2, and IL-11ra were up-regulated in macrophages.
      The results of the functional assays revealed that beta-TCP caused a prominent
      reduction in antigen uptake by DCs, and that conditioned medium from DCs treated
      with beta-TCP facilitated the migration of splenocytes in the transwell migration
      assay. Thus, beta-TCP induced phenotypical and functional maturation/activation
      of DCs and macrophages; these stimulating effects may contribute to the observed
      in vivo effect where beta-TCP induced extensive migration of immune cells. When
      compared to lipopolysaccharide (LPS), an authentic TLR ligand, the stimulatory
      effect of beta-TCP on the immune systems is mild to moderate; however, it may
      have some advantages as a novel immunomodulator. This is the first report on the
      direct in vitro effects of beta-TCP against bone marrow-derived DCs and
      macrophages.

PMID- 27697727
TI  - Development and application of a multi-component LC-MS/MS method for
      determination of designer benzodiazepines in urine.
AB  - New psychoactive substances (NPS) have become an increasing drug problem in the
      past decade. For detection of NPS, new analytical methods have to be developed,
      and the methods also have to be updated regularly. This study aimed at developing
      a multi-component LC-MS/MS method for detection and quantification of 11 NPS of
      the benzodiazepine sub-class ("designer benzodiazepines") in urine specimens. The
      method involves dilution of urine with internal standard and hydrolysis of any
      glucuronide conjugated forms. Separation of the compounds was achieved on a BEH
      Phenyl column, followed by MS/MS detection in positive electrospray mode. Method
      validation was performed following the EMA guideline. The method was applied to
      study the occurrence of designer benzodiazepines in Sweden in 2014-2015, by
      analysis of 390 samples retrieved from a routine drug testing laboratory. In 40%
      of these samples, selected based on a positive immunoassay benzodiazepine
      screening but a negative MS confirmation for the standard set of prescription
      benzodiazepines, intake of designer benzodiazepines was revealed. These results
      stress the importance of using and updating confirmation methods to include the
      increasing number of designer benzodiazepines appearing on the NPS market.

PMID- 27697726
TI  - Prevention of azoxymethane/dextran sodium sulfate-induced mouse colon
      carcinogenesis by processed Aloe vera gel.
AB  - The preventive effect of a processed Aloe vera gel (PAG) on colon carcinogenesis
      was examined using an azoxymethane (AOM)-initiated and dextran sodium sulfate
      (DSS)-promoted mouse colon carcinogenesis model. Oral administration of PAG (200,
      or 400mg/kg/day) significantly reduced the multiplicity of colonic adenomas and
      adenocarcinomas compared with the AOM/DSS only-treated mice. In the mice treated
      with 400mg/kg of PAG, adenoma and adenocarcinoma development was reduced to 80%
      and 60%, respectively, compared to 100% in the PAG-untreated AOM/DSS-treated
      mice. Western blot analysis using colon extracts showed that PAG reduced the
      activation of nuclear factor kappa B (NF-kappaB), resulting in the inhibition of
      inducible nitric oxide synthase and cyclooxygenase-2 expression. PAG appeared to
      inhibit the NF-kappaB activation through the activation of peroxisome
      proliferator-activated receptor gamma. PAG also inhibited the expression and
      phosphorylation of signal transducer and activator of transcription 3, which is
      known to connect inflammation and cancer. In addition, PAG inhibited cell cycle
      progression-inducing cellular factors, such as extracellular signal-regulated
      kinases 1/2, cyclin-dependent kinase 4, and cyclin D1. On the other hand, PAG
      increased the expression of Caudal-related homeobox transcription factor 2, which
      is known to be a tumor suppressor in colorectal cancer. These findings show that
      PAG suppresses colitis-related colon carcinogenesis by inhibiting both chronic
      inflammation and cell cycle progression in the colon.

PMID- 27697728
TI  - An easy-to-use liquid chromatography assay for the analysis of lamotrigine in rat
      plasma and brain samples using microextraction by packed sorbent: Application to
      a pharmacokinetic study.
AB  - A simple and rapid high-performance liquid chromatography method with diode-array
      detection (HPLC-DAD) using microextraction by packed sorbent (MEPS) during the
      sample preparation step was developed and validated to quantify lamotrigine (LTG)
      in rat plasma and brain samples. MEPS variables such as pH, number of draw-eject
      cycles, and washing and desorption conditions were optimized. The chromatographic
      resolution of LTG and chloramphenicol, used as internal standard (IS), was
      accomplished in less than 5min on a C18 column, at 35 degrees C, using an
      isocratic elution with acetonitrile (13%), methanol (13%) and water-triethylamine
      (99.7:0.3, v/v; pH 6.0) pumped at a flow rate of 1mL/min. Detection was performed
      at 215nm. Calibration curves were linear over the range of 0.1-20MUg/mL
      (r2>=0.9947) for LTG in both rat plasma and brain homogenate samples. The intra
      and interday imprecision did not exceed 8.6% and the intra and interday
      inaccuracy ranged from -8.1 to 13.5%. LTG was extracted from rat plasma and brain
      homogenate samples with an average absolute recovery ranging from 68.0 to 86.7%,
      and its stability was demonstrated in the assayed conditions. No interferences
      were observed at the retention times of the analyte (LTG) and IS. To the best of
      our knowledge, this is the first bioanalytical assay that uses MEPS procedure for
      the determination of LTG not only in rat plasma but also in tissue (brain)
      samples. This novel method was successfully applied to a preliminary
      pharmacokinetic study in rats and it seems to be a cost-effective tool to support
      non-clinical pharmacokinetic-based studies involving LTG treatment.

PMID- 27697729
TI  - Method development and validation for simultaneous quantitation of endogenous
      hippuric acid and phenylacetylglycine in rat urine using liquid chromatography
      coupled with electrospray ionization tandem mass spectrometry.
AB  - Urinary hippuric acid (HA) and phenylacetylglycine (PAG) are biomarker candidates
      for drug-induced phospholipidosis (PLD). To confirm their utility in preclinical
      and clinical settings, it is essential to develop and validate their
      quantification method in advance. In this study, we have applied liquid
      chromatography-tandem mass spectrometry (LC/MS/MS) for simultaneous
      quantification of HA and PAG in rat urine, and matrix based ion suppression was
      assessed by post-column infusion assay. Effective sample dilution reduced matrix
      effect of urine to be negligible level and calibration curves showed good
      correlation between those in urine diluent and buffer alone. Reliability of this
      assay was confirmed by the assessments for intra- and inter-day precisions and
      accuracies of quality control samples. The method was applied to rat urine after
      multiple oral administrations of PLD-inducing drugs, and the changes in HA and
      PAG concentrations and their ratio were successfully detected as rat plasma in
      previous report. This is the first report to quantify HA and PAG easily and
      accurately as potential biomarkers to monitor PLD status. This assay would be
      useful tool for monitoring PLD in toxicological studies by non-invasive sampling.

PMID- 27697730
TI  - Method for determination of streptomycin and streptidine as markers for
      streptomycin industrial dregs monitoring in pig and poultry compound feeds.
AB  - Antibiotic industrial dregs, generated from the production of antibiotics by
      fermentation, are banned in China as animal feed additives. Official monitoring
      programs require the analysis of feeds for possible illegal use of the dregs. A
      rapid and sensitive method was developed for the simultaneous determination of
      streptomycin and streptidine as markers for streptomycin industrial dregs in pig
      and poultry compound feeds. After extraction with 20% aqueous trichloroacetic
      acid and pH adjustment, sample cleanup was performed by weak cation-exchange
      solid-phase extraction. UPLC-ESI-MS/MS was carried out using a hydrophilic
      interaction chromatography(HILIC)column to achieve separation. Quantification
      required matrix-matched calibrations in a linear range of 50-1000MUgkg-1; the
      calibration curves were linear in this range with coefficients of determination
      of 0.991 and 0.994 for streptomycin and streptidine, respectively. The method
      validity parameters-LODs (20MUgkg-1) and LOQs (50MUgkg-1), recoveries (71-78% and
      75-84%, respectively), and relative reproducibility (5.4-9.6%)-satisfy the
      requirements of routine analysis.

PMID- 27697731
TI  - Identification and quantification of synthetic cathinones in blood and urine
      using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass
      spectrometry.
AB  - Synthetic cathinones continue to present a formidable challenge to forensic
      toxicology laboratories despite the fact that they are often encountered in
      impaired driving and death investigations. Due to limitations in immunoassay
      based screening technologies, many forensic toxicology laboratories must rely on
      more labor intensive chromatographic-based screening approaches in order to
      detect these drugs in biological evidence. Solid phase extraction (SPE) and
      liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry were
      used to identify twenty-two synthetic cathinones in urine and blood. Target drugs
      included methcathinone, ethcathinone, pentedrone, buphedrone, 3
      fluoromethcathinone (3-FMC), 4-fluoromethcathinone (4-FMC), 4-methylethcathinone
      (4-MEC), 4-ethylmethcathinone (4-EMC), mephedrone, methedrone, 3,4
      dimethylmethcathinone (3,4-DMMC), ethylone, butylone, pentylone, eutylone,
      methylone, methylenedioxypyrovalerone (MDPV), 4-methylpyrrolidinobutiophenone
      (MPBP), 3,4-methylenedioxypyrrolidinobutiophenone (MDPBP), alpha
      pyrrolidinopentiphenone (alpha-PVP), pyrovalerone, and naphyrone. A total of nine
      deuterated internal standards were employed. Using traditional reversed phase
      chromatography all positional isomers, including 3-FMC and 4-FMC, were separated
      in 12min. The procedure was validated in accordance with the Scientific Working
      Group for Forensic Toxicology (SWGTOX) Standard Practices for Method Validation.
      Extraction efficiencies were 84-104% and 81-93% in urine and blood, respectively.
      Limits of quantitation in both matrices were 0.25-5ng/mL. Precision, bias and
      matrix effect were all within acceptable thresholds and the assay was free from
      more than fifty interferences. The validated method was used to identify
      cathinones in authentic urine case samples (n=20) and these results highlight
      important considerations for cathinone stability and the subsequent
      interpretation of results.

PMID- 27697732
TI  - Assessment of maturity indices of rock phosphate enriched composts using variable
      crop residues.
AB  - This study aimed to asses maturity indices of rock phosphate enriched composts
      using crop residues having variable C/N ratios. There were distinct differences
      in concentration of NH4+-N, NO3--N, Olsen-P and NH4OAc-K for composts generated
      from different crop residues, the highest being in rice straw. Water soluble P
      varied from 3.47-4.45% of total P, while citrate soluble P varied from 32.7-54.0%
      of total P. Rice straw composts showed lower C/N, WSC/Org-N and E4/E6 ratio and
      higher germination index indicating that they are well-matured and stabilized
      compost. The relative order of performance of crop residues in aggrading compost
      quality was chickpea stover>rice straw>mustard stover>wheat straw>tree leaves.
      The results demonstrated that all the enriched composts had higher contents of
      available nutrients and quality indices, indicating that enriched composts could
      be used to substitute costly chemical fertilizers for crop production.

PMID- 27697733
TI  - A novel recycling system for nano-magnetic molecular imprinting immobilised
      cellulases: Synergistic recovery of anthocyanin from fruit and vegetable waste.
AB  - Fruit and vegetable waste (FVW) is become a serious problem in developing
      countries. Enzymolysis is a potentially useful method for the treatment of FVW.
      In the present study, novel recycled magnetic molecular imprinting immobilised
      cellulases were prepared based on magnetic modified chitosan (MCTS) and Fe3O4.
      The properties of obtained were characterised by IR and grain-size measurements.
      Evaluation of a single factor affecting the loading efficiency of supports and
      the mixed immobilised enzymes showed better capacity than single immobilised, or
      free, enzymes. The immobilisation process could improve cellulase stability and
      repeatability of the method. Meanwhile, the kinetic parameters were also
      verified. The immobilised enzymes retained most of their capacity after 60days'
      storage while free enzymes lost it within 30days. Tests showed that the
      immobilised enzymes developed excellent capacity and five anthocyanins were
      collected.

PMID- 27697734
TI  - Omics-based approaches reveal phospholipids remodeling of Rhizopus oryzae
      responding to furfural stress for fumaric acid-production from xylose.
AB  - In order to relieve the toxicity of furfural on Rhizopus oryzae fermentation, the
      molecular mechanism of R. oryzae responding to furfural stress for fumaric acid
      production was investigated by omics-based approaches. In metabolomics analysis,
      29 metabolites including amino acid, sugars, polyols and fatty acids showed
      significant changes for maintaining the basic cell metabolism at the cost of
      lowering fumaric acid production. To further uncover the survival mechanism,
      lipidomics was carried out, revealing that phosphatidylcholine,
      phosphatidylglycerol, phosphatidylinositol and polyunsaturated acyl chains might
      be closely correlated with R. oryzae's adapting to furfural stress. Based on the
      above omics analysis, lecithin, inositol and soybean oil were exogenously
      supplemented separately with an optimized concentration in the presence of
      furfural, which increased fumaric acid titer from 5.78g/L to 10.03g/L, 10.05g/L
      and 12.13g/L (increased by 73.5%, 73.8% and 110%, respectively). These findings
      provide a methodological guidance for hemicellulose-fumaric acid development.

PMID- 27697735
TI  - Treatment of anaerobically digested swine wastewater by Rhodobacter blasticus and
      Rhodobacter capsulatus.
AB  - Two strains of photosynthetic bacteria, Rhodobacter blasticus and Rhodobacter
      capsulatus, were used in this work to investigate the feasibility of using
      photosynthetic bacteria for the treatment of anaerobically digested swine
      wastewater. The effects of crucial factors which influence the pollutants removal
      efficiency were also examined. Results showed that anaerobically digested swine
      wastewater could be treated effectively by photosynthetic bacteria. The treatment
      efficiency was significantly higher by the mixed photosynthetic bacteria than
      that by any unitary bacterium. The optimal treatment condition by mixed bacteria
      was inoculation of 10.0%(v/v) of the two bacteria by 1:1, initial pH of 7.0 and
      initial chemical oxygen demand of 4800mgL-1. Under these conditions, the removal
      rate of chemical oxygen demand was 83.3%, which was 19.3% higher than when using
      Rhodobacter blasticus or 10.6% higher than when using Rhodobacter capsulatus
      separately. This mixed photosynthetic bacteria achieved high chemical oxygen
      demand removal and cell yields.

PMID- 27697736
TI  - Mathematical modeling of nitrous oxide production in an anaerobic/oxic/anoxic
      process.
AB  - This study incorporates three currently known nitrous oxide (N2O) production
      pathways: ammonium-oxidizing bacteria (AOB) denitrification, incomplete
      hydroxylamine (NH2OH) oxidation, and heterotrophic denitrification on
      intracellular polymers, into a mathematical model to describe N2O production in
      an anaerobic/oxic/anoxic (AOA) process for the first time. The developed model
      was calibrated and validated by four experimental cases, then evaluated by two
      independent anaerobic/aerobic (AO) studies from literature. The modeling results
      displayed good agreement with the measured data. N2O was primarily generated in
      the aerobic stage by AOB denitrification (67.84-81.64%) in the AOA system.
      Smaller amounts of N2O were produced via incomplete NH2OH oxidation (15.61
      32.17%) and heterotrophic denitrification on intracellular polymers (0-12.47%).
      The high nitrite inhibition on N2O reductase led to the increased N2O
      accumulation in heterotrophic denitrification on intracellular polymers. The new
      model was capable of modeling nitrification-denitrification dynamics and
      heterotrophic denitrification on intracellular polymers in the AOA system.

PMID- 27697737
TI  - A three-dimensional spatial characterization of the crossed-hands deficit.
AB  - To perceive the location of touch in space, we integrate information about skin
      location with information about the location of that body part in space. Most
      research investigating this process of tactile spatial remapping has used the so
      called crossed-hands deficit, in which the ability to judge the temporal order of
      touches on the two hands is impaired when the arms are crossed. This posture
      induces a conflict between skin-based and tactile external spatial
      representations, specifically in the left-right dimension. Thus, it is unknown
      whether touch is affected by posture when spatial relations other than the right
      left dimension are available. Here, we tested the extent to which the crossed
      hands deficit is a measure of tactile remapping, reflecting tactile encoding in
      three-dimensional space. Participants judged the temporal order of tactile
      stimuli presented to crossed and uncrossed hands. The arms were placed at
      different elevations (up-down dimension; Experiments 1 and 2), or at different
      distances from the body in the depth plane (close-far dimension; Experiment 3).
      The crossed-hands deficit was reduced when other sources of spatial information,
      orthogonal to the left-right dimension (i.e., close-far, up-down), were
      available. Nonetheless, the deficit persisted in all conditions, even when
      processing of non-conflicting information in the close-far or up-down dimensions
      was enough to solve the task. Together, these results demonstrate that the
      processing underlying the crossed-hands deficit is related to the encoding of
      tactile localization in three-dimensional space, rather than related uniquely to
      the cost of processing information in the right-left dimension. Furthermore, the
      persistence of the crossing effect provides evidence for automatic integration of
      all available information during the encoding of tactile information.

PMID- 27697738
TI  - Langmuir films of dipalmitoyl phosphatidylethanolamine grafted poly(ethylene
      glycol). In-situ evidence of surface aggregation at the air-water interface.
AB  - The molecular packing-dependent interfacial organization of polyethylene glycol
      grafted dipalmitoylphosphatidylethanolamine (PE-PEGs) Langmuir films was studied.
      The PEG chains covered a wide molecular mass range (350, 1000 and 5000Da). In
      surface pressure-area (pi-A), isotherms PE-PEG1000 and PE-PEG5000 showed
      transitions (midpoints at pim,t1~11mN/m, "t1"), which appeared as a long non
      horizontal line region. Thus, t1 cannot be considered a first-order phase
      transition but may reflect a transition within the polymer, comprising its
      desorption from the air-water interface and compaction upon compression. This is
      supported by the increase in the nus(C-O-C) PM-IRRAS signal intensity and the
      increasing surface potentials at maximal compression, which reflect thicker
      polymeric layers. Furthermore, changes in hydrocarbon chain (HC) packing and tilt
      with respect to the surface led to reorientation in the PO2- group upon
      compression, indicated by the inversion of the nuasym(PO2-) PM-IRRAS signal
      around t1. The absence of a t1 in PE-PEG350 supports the requisite of a critical
      polymer chain length for this transition to occur. In-situ epifluorescence
      microscopy revealed 2D-domain-like structures in PE-PEG1000 and PE-PEG5000 around
      t1, possibly associated with gelation/dehydration of the polymeric layer and
      appearing at decreasing pi as the polymeric tail became longer. Another
      transition, t2, appearing in PE-PEG350 and PE-PEG1000 at pim,t2=29.4 and
      34.8mN/m, respectively, was associated with HC condensation and was impaired in
      PE-PEG5000 due to steric hindrance imposed by the large size of its polymer
      moiety. Two critical lengths of polymer chains were found, one of which allowed
      the onset of polymeric-tail gelation and the other limited HC compaction.

PMID- 27697739
TI  - Nanocarriers enhance the transdermal bioavailability of resveratrol: In-vitro and
      in-vivo study.
AB  - The aim of this study was to develop and assess the potential of nanostructured
      emulsion carriers for resveratrol topical application. Different compositions of
      resveratrol-loaded nanostructured emulsions were prepared using different types
      and amounts of surfactants and oily phases (isopropyl myristate and caproyl 90).
      The produced nanostructured emulsions were within the nanosized range 23.4
      422.2nm with low viscosity range 2.15-17.53cps. The transdermal amount and
      deposition amount in the skin after 24 applications of resveratrol-loaded
      nanostructured emulsion were significantly increased about 896.2-fold and 10.2
      fold respectively, when compared to the drug-saturated solution-treated group.
      Nanostructured emulsion containing IPM and low amounts of mixed surfactant of
      Tween80/Span 20 showed highest permeation capacity. In vivo study showed that the
      plasma concentration of resveratrol could be maintained at high levels for a long
      time after topical application of drug-loaded nanostructured emulsion. The
      histological examination demonstrated that the free drug- and drug-loaded
      nanostructured emulsion demonstrated considerably less irritation than the
      standard irritation group (0.8% paraformaldehyde-treated). The residual contents
      of resveratrol in the tested formulations after 3 months of storage at 25 degrees
      C and 40 degrees C were more than 99.97+/-3.90%. The results of present work
      confirm the high potential of nanostructured emulsion as carriers for drug
      topical application.

PMID- 27697740
TI  - Mechanism of adsorption of single and double stranded DNA on gold and silver
      nanoparticles: Investigating some important parameters in bio-sensing
      applications.
AB  - The mechanism of adsorption of single and double stranded DNAs on colloidal gold
      and silver nanoparticles has been studied by measuring the resistance of the
      nanoparticles, surrounded by various oligonucleotides, against salt induced
      aggregation. It is shown that both single and double stranded DNAs can be
      adsorbed on the metal nanoparticles and the adsorption strength is determined by
      the interaction between various bases of DNA and the nanoparticles. By changing
      the salt concentration, the difference between adsorption of various DNA strands
      on the nanoparticles can be specified. The results indicate that a key parameter
      in success of a sensing assay of DNA hybridization is the salt concentration
      which should be greater than a minimum threshold depending on the nanoparticles
      characteristics. We have also investigated the interaction mechanism between
      various DNA bases with the metal nanoparticles. For both gold and silver
      nanoparticles, adenine has the highest and thymine has the lowest attachment to
      the nanoparticles. From surface enhanced Raman spectroscopy (SERS) data of
      various bases in the presence of gold nanoparticles, the probable interaction
      points in the bases with the nanoparticles have been determined, which are mainly
      the nitrogen sites of these oligonucleotides.

PMID- 27697741
TI  - Impacts of low socioeconomic status and polycyclic aromatic hydrocarbons exposure
      on lung function among a community-based Chinese population.
AB  - Lung function is related to socioeconomic status (SES) and exposure to polycyclic
      aromatic hydrocarbons (PAHs). However, joint effect of SES and exposure to PAHs
      on lung function has been largely unknown. We aimed to investigate joint effects
      of SES and urinary OH-PAHs levels on lung function parameters. This study
      included 2739 Wuhan participants from the baseline survey of the Wuhan-Zhuhai
      (WHZH) Cohort Study (n=3053). They completed the questionnaire, physical
      examination and provided blood and urine samples. Twelve urinary monohydroxy-PAHs
      metabolites (OH-PAHs) and lung function were measured by gas chromatography-mass
      spectrometry and digital spirometers, respectively. Individuals with low
      educational levels and low or high levels of urinary SigmaOH-PAHs had a 3.5% (95%
      CI: -5.4, -1.6%) or 4.2% (95% CI: -6.1, -2.3%) reduction in the ratio of forced
      expiratory volume in 1s to forced vital capacity (FEV1/FVC), respectively, and
      those with middle levels of education and high levels of urinary SigmaOH-PAHs had
      a 2.1% (95% CI: -5.4, -1.6%) reduction in the FEV1/FVC ratio, rather than those
      with high levels of education and low levels of urinary SigmaOH-PAHs. Individuals
      with low levels of education had a -3.0% (95% CI: -4.4, -1.6%) reduction in
      FEV1/FVC compared with individuals with high levels of education. Urinary OH-PAHs
      levels were marginally negatively related to FEV1 in all participants (p=0.073).
      The results indicated that there was a prominent effect of low levels of
      education and higher exposure to PAHs on lung function decline, indicating that
      it is a necessary to take measures to promote the education level and reduce
      exposure to environmental PAHs.

PMID- 27697742
TI  - The oxygen isotopic composition of phosphate in river water and its potential
      sources in the Upper River Taw catchment, UK.
AB  - The need to reduce both point and diffuse phosphorus pollution to aquatic
      ecosystems is widely recognised and in order to achieve this, identification of
      the different pollutant sources is essential. Recently, a stable isotope approach
      using oxygen isotopes within phosphate (delta18OPO4) has been used in phosphorus
      source tracing studies. This approach was applied in a one-off survey in
      September 2013 to the River Taw catchment in south-west England where elevated
      levels of phosphate have been reported. River water delta18OPO4 along the main
      channel varied little, ranging from +17.1 to +18.80/00. This was no >0.30/00
      different to that of the isotopic equilibrium with water (Edelta18OPO4). The
      delta18OPO4 in the tributaries was more variable (+17.1 to +18.80/00), but only
      deviated from Edelta18OPO4 by between 0.4 and 0.90/00. Several potential
      phosphate sources within the catchment were sampled and most had a narrow range
      of delta18OPO4 values similar to that of river Edelta18OPO4. Discharge from two
      waste water treatment plants had different and distinct delta18OPO4 from one
      another ranging between +16.4 and +19.60/00 and similar values to that of a dairy
      factory final effluent (+16.5 to +17.80/00), mains tap water (+17.8 to
      +18.40/00), and that of the phosphate extracted from river channel bed sediment
      (+16.7 to +17.60/00). Inorganic fertilizers had a wide range of values (+13.3 to
      +25.90/00) while stored animal wastes were consistently lower (+12.0 to
      +15.00/00) than most other sources and Edelta18OPO4. The distinct signals from
      the waste water treatment plants were lost within the river over a short distance
      suggesting that rapid microbial cycling of phosphate was occurring, because
      microbial cycling shifts the isotopic signal towards Edelta18OPO4. This study has
      added to the global inventory of phosphate source delta18OPO4 values, but also
      demonstrated the limitations of this approach to identifying phosphate sources,
      especially at times when microbial cycling is high.

PMID- 27697743
TI  - EGR-1 is an active transcription factor in TGF-beta2-mediated small intestinal
      cell differentiation.
AB  - Human milk contains growth factors that maintain intestinal mucosal homeostasis,
      but the molecular mechanisms behind how these growth factors regulate gene
      transcription are largely unknown. In this study, IEC-6 (rat intestinal
      epithelial cells) cells were used as a model to study cell differentiation
      mediated by transforming growth factor-beta2 (TGF-beta2), the most abundant
      growth factor in human milk. We focused on the transcription factor early growth
      response-1 (EGR-1), as we found a robust and rapid response in our initial
      transcription factor screen. Immunoblotting and immunofluorescent assays
      confirmed the phenotype change upon TGF-beta2 treatment and EGR-1 stimulation in
      the nucleus, with maximum expression occurring at 1 h. Chromatin
      immunoprecipitation sequencing was performed to map genome-wide EGR-1 binding
      sites on more than 1800 genes, widely involved in processes such as gene
      expression, transcription, membrane invagination and metabolism. In particular,
      more than 15 Wnt signaling pathway genes have EGR-1 binding sites; among them,
      Axin1 was the limiting factor, ensuring proper beta-catenin accumulation in the
      cytoplasm. We further used chromatin immunoprecipitation quantitative PCR to
      validate that EGR-1 binds to the region of -636/-454 bp and -454/-200 bp of the
      Axin1 promoter and functionally activates gene expression. The effect of TGF
      beta2 on maintaining small intestinal cell homeostasis was partially explained by
      Axin1 activation through EGR-1.

PMID- 27697744
TI  - Ternary nanohybrid of reduced graphene oxide-nafion@silver nanoparticles for
      boosting the sensor performance in non-enzymatic amperometric detection of
      hydrogen peroxide.
AB  - A sensitive and novel electrochemical sensor was developed for the detection of
      hydrogen peroxide (H2O2) using a reduced graphene oxide-nafion@silver6 (rGO
      Nf@Ag6) nanohybrid modified glassy carbon electrode (GC/rGO-Nf@Ag6). The GC/rGO
      Nf@Ag6 electrode exhibited an excellent electrochemical sensing ability for
      determining H2O2 with high sensitivity and selectivity. The detection limit of
      the electrochemical sensor using the GC/rGO-Nf@Ag6 electrode for H2O2
      determination was calculated to be 5.35*10-7M with sensitivity of 0.4508uAuM-1.
      The coupling between rGO-Nf with silver nanoparticles (AgNPs) significantly
      boosted the electroanalytical performance by providing more active area for
      analyte interaction, thereby allowing more rapid interfacial electron transfer
      process. The interfering effect on the current response of H2O2 was studied and
      the results revealed that the sensor electrode exhibited an excellent immunity
      from most common interferents. The proposed non-enzymatic electrochemical sensor
      was used for determining H2O2 in apple juice, and the sensor electrode provided
      satisfactory results with reliable recovery values. These studies revealed that
      the novel GC/rGO-Nf@Ag6 sensor electrode could be a potential candidate for the
      detection of H2O2.

PMID- 27697745
TI  - Halide removal from aqueous solution by novel silver-polymeric materials.
AB  - The objective of this study was to analyze the behavior of a new material, silver
      doped polymeric cloth (Ag-cloth), in the removal of bromide and iodide from
      waters. Silver is immobilized on the cloth, guaranteeing selective adsorption of
      the halide ions as retained silver halides that therefore do not pass into the
      solution. Results indicate that Ag0 reacts with H2O2 in the first phases of the
      process, yielding Ag+ and superoxide radical; however, as the process advances,
      this radical favors Ag+ reduction. Increases in the concentration of H2O2 augment
      the capacity of the Ag-cloth to remove halides from the medium up to a maximum
      concentration (55MUM), above which the removal capacity remains constant (Xm?1.3
      1.8mg halide/g Ag-cloth). Thus, when there is excess H2O2 in the medium,
      secondary competitive reactions that take place in the process guarantee a
      constant Ag+ concentration, which defines the maximum adsorption capacity of Ag
      cloth, reducing its ability to remove halides. Ag-cloth has a higher capacity to
      remove iodide than bromide, and the presence of organic matter or chloride
      reduces its capacity to remove iodide or bromide from water. The results obtained
      shown that the capacity of Ag0 with H2O2 significantly varies as a function of
      the medium pH from 1mg Br-/g Ag-cloth at very low pH to 1.6mg/g Ag-cloth at pH9.

PMID- 27697746
TI  - Atypical reactivity of heart rate variability to stress and depression across
      development: Systematic review of the literature and directions for future
      research.
AB  - Heart rate variability has received growing attention in the depression
      literature, with several recent meta-analyses indicating that lower resting heart
      rate variability is associated with depression. However, the role of fluctuations
      in heart rate variability (or reactivity) in response to stress in depression
      remains less clear. The present review provides a systematic examination of the
      literature on heart rate variability reactivity to a laboratory-induced stressor
      task and depression, including 26 studies of reactivity in heart rate variability
      and clinical depression, remitted (or history of) depression, and subthreshold
      depression (or symptom-level depression) among adults, adolescents, and children.
      In addition to reviewing the findings of these studies, methodological
      considerations and conceptual gaps in the literature are addressed. We conclude
      by highlighting the importance of investigating the potential transactional
      relationship between heart rate variability reactivity and depression and
      possible mechanisms underlying this relationship.

PMID- 27697747
TI  - Are Fish Consumption Advisories for the Great Lakes Adequately Protective against
      Chemical Mixtures?
AB  - BACKGROUND: The North American Great Lakes are home to > 140 types of fish and
      are famous for recreational and commercial fishing. However, the presence of
      toxic substances has resulted in the issuance of fish consumption advisories that
      are typically based on the most restrictive contaminant. OBJECTIVES: We
      investigated whether these advisories, which typically neglect the existence of a
      mixture of chemicals and their possible additive adverse effects, are adequately
      protective of the health of humans consuming fish from the Canadian waters of the
      Great Lakes. METHODS: Using recent fish contaminant monitoring data collected by
      the government of Ontario, Canada, we simulated advisories using most-restrictive
      contaminant (one-chem) and multi-contaminant additive effect (multi-chem)
      approaches. The advisories from the two simulations were compared to determine if
      there is any deficiency in the currently issued advisories. RESULTS:
      Approximately half of the advisories currently issued are potentially not
      adequately protective. Of the four Great Lakes studied, the highest percentage of
      advisories affected are in Lake Ontario if an additive effect is considered. Many
      fish that are popular for consumption, such as walleye, salmon, bass and trout,
      would have noticeably more stringent advisories. CONCLUSIONS: Improvements in the
      advisories may be needed to ensure that the health of humans consuming fish from
      the Great Lakes is protected. In this region, total polychlorinated biphenyls
      (PCBs) and mercury are the major contaminants causing restrictions on consuming
      fish, whereas dioxins/furans, toxaphene, and mirex/photomirex are of minor
      concern. Regular monitoring of most organochlorine pesticides and metals in fish
      can be discontinued.

PMID- 27697749
TI  - ENHANCE-(Electronic Hydroxyurea Adherence): A Protocol to Increase Hydroxyurea
      Adherence in Patients with Sickle Cell Disease.
AB  - BACKGROUND: Hydroxyurea (HU) is the only disease-modifying medication for
      patients with sickle cell disease (SCD). HU can reduce SCD-related complications
      but only 35% to 50% of pediatric patients adhere to HU at the rates achieved in
      clinical trials and this limits its clinical effectiveness. Mobile Directly
      Observed Therapy (Mobile DOT) is a pilot-tested, electronic, multidimensional, HU
      adherence intervention that targets many components of the Health Behavior Model.
      OBJECTIVE: The aim of this study is to evaluate the impact of Mobile DOT on HU
      adherence in children with SCD. The objective of our study is to inform the
      development of future adherence interventions and pediatric SCD protocols.
      METHODS: This is a single-arm crossover study of pediatric patients with SCD.
      Participants self-record videos of their daily HU administrations and receive
      text message alerts to take HU, feedback on their HU adherence, and incentives
      when they achieve adherence goals during the 6-month Mobile DOT phase.
      Participants' HU adherence during the Mobile DOT phase is compared with their
      baseline HU adherence (6 months prior to study entry) and to their HU adherence 6
      months after completing the Mobile DOT phase. The primary outcome of this study
      is HU adherence measured by medication possession ratio. RESULTS: The trial is
      ongoing. Preliminary review of participant satisfaction results suggest that most
      participants can complete Mobile DOT in less than 5 minutes per day and are
      satisfied with the intervention. CONCLUSIONS: If effective, the Mobile DOT
      strategy will increase HU adherence and this could improve patients' clinical
      outcomes and reduce costs of care.

PMID- 27697748
TI  - "I Want to Keep the Personal Relationship With My Doctor": Understanding Barriers
      to Portal Use among African Americans and Latinos.
AB  - BACKGROUND: Despite the widespread implementation of electronic health records
      (EHRs), there is growing evidence that racial/ethnic minority patients do not use
      portals as frequently as non-Hispanic whites to access their EHR information
      online. This differential portal use could be problematic for health care
      disparities since early evidence links portal use to better outcomes. OBJECTIVE:
      We sought to understand specific barriers to portal use among African American
      and Latino patients at Kaiser Permanente, which has had a portal in place for
      over a decade, and broad uptake among the patient population at large. METHODS:
      We conducted 10 focus groups with 87 participants in 2012 and 2013 among African
      American and Latino Kaiser Permanente members in the mid-Atlantic, Georgia, and
      Southern California regions. Members were eligible to participate if they were
      not registered for portal access. Focus groups were conducted within each
      racial/ethnic group, and each included individuals who were older, had a chronic
      disease, or were parents (as these are the three biggest users of the portal at
      Kaiser Permanente overall). We videotaped each focus group and transcribed the
      discussion for analysis. We used general inductive coding to develop themes for
      major barriers to portal use, overall and separately by racial/ethnic group.
      RESULTS: We found that lack of support was a key barrier to initiating portal use
      in our sample-both in terms of technical assistance as well as the fear of the
      portal eroding existing personal relationships with health care providers. This
      held true across a range of focus groups representing a mix of age, income,
      health conditions, and geographic regions. CONCLUSIONS: Our study was among the
      first qualitative explorations of barriers to portal use among racial/ethnic
      subgroups. Our findings suggest that uniform adoption of portal use across
      diverse patient groups requires more usable and personalized websites, which may
      be particularly important for reducing health care disparities. This work is
      particularly important as all health care systems continue to offer and promote
      more health care features online via portals.

PMID- 27697750
TI  - Assessing the Impact and Cost of Short-Term Health Workforce in Remote Indigenous
      Communities in Australia: A Mixed Methods Study Protocol.
AB  - BACKGROUND: Remote Australia is a complex environment characterized by workforce
      shortages, isolated practice, a large resident Indigenous population, high levels
      of health need, and limited access to services. In recent years, there has been
      an increasing trend of utilizing a short-term visiting (fly-in/fly-out) health
      workforce in many remote areas. However, there is a dearth of evidence relating
      to the impact of this transitory workforce on the existing resident workforce,
      consumer satisfaction, and the effectiveness of current services. OBJECTIVE: This
      study aims to provide rigorous empirical data by addressing the following
      objectives: (1) to identify the impact of short-term health staff on the
      workload, professional satisfaction, and retention of resident health teams in
      remote areas; (2) to identify the impact of short-term health staff on the
      quality, safety, and continuity of patient care; and (3) to identify the impact
      of short-term health staff on service cost and effectiveness. METHODS: Mixed
      methods will be used. Administrative data will be extracted that relates to all
      54 remote clinics managed by the Northern Territory Department of Health,
      covering a population of 35,800. The study period will be 2010 to 2014. All 18
      Aboriginal Community-Controlled Health Services in the Northern Territory will
      also be invited to participate. We will use these quantitative data to describe
      staffing stability and turnover in these communities, and then utilize multiple
      regression analyses to determine associations between the key independent
      variables of interest (resident staff turnover, stability or median survival, and
      socioeconomic status, community size, and per capita funding) and dependent
      variables related to patient care, service cost, quality, and effectiveness. The
      qualitative component of the study will involve in-depth interviews and focus
      groups with staff and patients, respectively, in six remote communities. Three
      communities will be high staff turnover communities and three characterized by
      low turnover. This will provide information on service quality, impact on
      resident and visiting staff, and patient satisfaction with the services. The
      research team will work with staff, patients, and a key stakeholder group of
      senior policymakers to develop workforce strategies to maintain or attain remote
      health workforce stability. RESULTS: The study commenced in 2015. As of October
      2016, fieldwork has been almost completed and quantitative analysis has
      commenced. Results are expected to be published in 2017. CONCLUSIONS: The study
      has commenced, but it is too early to provide results or conclusions.

PMID- 27697751
TI  - MiR-495 functions as an adjuvant to radiation therapy by reducing the radiation
      induced bystander effect.
AB  - The radiation-induced bystander effect (RIBE) is an important factor in tumor
      radiation therapy because it may increase the probability of normal cellular
      injury and the likelihood of secondary cancers after radiotherapy. Here, we
      identified the role of miR-495 in alleviating RIBEs during radiotherapy.
      Luciferase reporter assay results confirmed that miR-495 regulated endothelial
      nitric oxide synthase (eNOS) by targeting the Sp1 3'-untranslated region.
      Consequently, after radiation, tumor cells expressed less eNOS and Sp1 than
      controls. In vitro cell irradiation data based on flow-cytometric analysis and
      enzymed linked immunosorbent assay confirmed that nitric oxide (NO) and its
      downstream product transforming growth factor beta1 (TGF-beta1) were critical
      signaling factors contributing to RIBEs. Fewer normal LO2 liver cells were
      injured and fewer micronuclei were observed when treated with the medium of the
      miR-495 overexpressing HepG2 and ZR75-1 tumor cells. Accordingly, treatment with
      the miR-495 antagomir led to higher NO and TGF-beta1 levels and more injured LO2
      cells. In vivo experiments indicated that local irradiation of tumors
      overexpressing miR-495 produced fewer necrotic foci in non-irradiated liver
      tissue compared with controls. miR-495 was upregulated in clinical cancer tissues
      compared with adjacent non-cancerous tissues, and radiation significantly reduced
      the expression level of miR-495 in carcinoma cell lines. In summary, miR-495 may
      have promise as an adjuvant for tumor radiation therapy to decrease RIBEs
      involving the Sp1/eNOS pathway.

PMID- 27697753
TI  - Recommendations to improve adverse event reporting in clinical trial
      publications: a joint pharmaceutical industry/journal editor perspective.

PMID- 27697754
TI  - Risk of leukaemia is no higher in children living near UK nuclear sites, finds
      report.

PMID- 27697752
TI  - Plasminogen Activator Inhibitor-1 and Diagnosis of the Metabolic Syndrome in a
      West African Population.
AB  - BACKGROUND: Metabolic syndrome (MetS) is diagnosed by the presence of at least 3
      of the following: obesity, hypertension, hyperglycemia, hypertriglyceridemia, and
      low high-density lipoprotein. Individuals with MetS also typically have elevated
      plasma levels of the antifibrinolytic factor, plasminogen activator inhibitor-1
      (PAI-1), but the relationships between PAI-1 and MetS diagnostic criteria are not
      clear. Understanding these relationships can elucidate the relevance of MetS to
      cardiovascular disease risk, because PAI-1 is associated with ischemic events and
      directly involved in thrombosis. METHODS AND RESULTS: In a cross-sectional
      analysis of 2220 Ghanaian men and women from urban and rural locales, we found
      the age-standardized prevalence of MetS to be as high as 21.4% (urban women). PAI
      1 level increased exponentially as the number of diagnostic criteria increased
      linearly (P<10-13), supporting the conclusion that MetS components have a joint
      effect that is stronger than their additive contributions. Body mass index,
      triglycerides, and fasting glucose were more strongly correlated with PAI-1 than
      with canonical MetS criteria, and this pattern did not change when pair-wise
      correlations were conditioned on all other risk factors, supporting an
      independent role for PAI-1 in MetS. Finally, whereas the correlations between
      conventional risk factors did not vary significantly by sex or across urban and
      rural environments, correlations with PAI-1 were generally stronger among urban
      participants. CONCLUSIONS: MetS prevalence in the West African population we
      studied was comparable to that of the industrialized West. PAI-1 may serve as a
      key link between MetS, as currently defined, and the endpoints with which it is
      associated. Whether this association is generalizable will require follow-up.

PMID- 27697756
TI  - Occurrence of mcr-1 in Colistin-Resistant Salmonella enterica Isolates Recovered
      from Humans and Animals in Italy, 2012 to 2015.

PMID- 27697755
TI  - Comparative Pharmacokinetic Profiling of Different Polymyxin B Components.
AB  - Polymyxin B is increasingly used as a treatment of last resort for multidrug
      resistant Gram-negative infections. Despite being available as a mixture of
      several structurally related analogues, the properties are commonly reported as
      an aggregate of the individual components. We compared the pharmacokinetics of
      individual polymyxin B components in an animal model and in humans. There were no
      considerable differences observed in the pharmacokinetics among major components
      of polymyxin B. Combining different components for pharmacokinetic analysis
      appeared reasonable.

PMID- 27697757
TI  - Liver Fatty Acid Binding Protein Deficiency Provokes Oxidative Stress,
      Inflammation, and Apoptosis-Mediated Hepatotoxicity Induced by Pyrazinamide in
      Zebrafish Larvae.
AB  - Pyrazinamide (PZA) is an essential antitubercular drug, but little is still known
      about its hepatotoxicity potential. This study examined the effects of PZA
      exposure on zebrafish (Danio rerio) larvae and the mechanisms underlying its
      hepatotoxicity. A transgenic line of zebrafish larvae that expressed enhanced
      green fluorescent protein (EGFP) in the liver was incubated with 1, 2.5, and 5 mM
      PZA from 72 h postfertilization (hpf). Different endpoints such as mortality,
      morphology changes in the size and shape of the liver, histological changes,
      transaminase analysis and apoptosis, markers of oxidative and genetic damage, as
      well as the expression of certain genes were selected to evaluate PZA-induced
      hepatotoxicity. Our results confirm the manner of PZA dose-dependent
      hepatotoxicity. PZA was found to induce marked injury in zebrafish larvae, such
      as liver atrophy, elevations of transaminase levels, oxidative stress, and
      hepatocyte apoptosis. To further understand the mechanism behind PZA-induced
      hepatotoxicity, changes in gene expression levels in zebrafish larvae exposed to
      PZA for 72 h postexposure (hpe) were determined. The results of this study
      demonstrated that PZA decreased the expression levels of liver fatty acid binding
      protein (L-FABP) and its target gene, peroxisome proliferator-activated receptor
      alpha (PPAR-alpha), and provoked more severe oxidative stress and hepatitis via
      the upregulation of inflammatory cytokines such as tumor necrosis factor alpha
      (TNF-alpha) and transforming growth factor beta (TGF-beta). These findings
      suggest that L-FABP-mediated PPAR-alpha downregulation appears to be a
      hepatotoxic response resulting from zebrafish larva liver cell apoptosis, and L
      FABP can be used as a biomarker for the early detection of PZA-induced liver
      damage in zebrafish larvae.

PMID- 27697758
TI  - Pharmacokinetic Interactions between Tafenoquine and Dihydroartemisinin
      Piperaquine or Artemether-Lumefantrine in Healthy Adult Subjects.
AB  - Tafenoquine is in development as a single-dose treatment for relapse prevention
      in individuals with Plasmodium vivax malaria. Tafenoquine must be coadministered
      with a blood schizonticide, either chloroquine or artemisinin-based combination
      therapy (ACT). This open-label, randomized, parallel-group study evaluated
      potential drug interactions between tafenoquine and two ACTs: dihydroartemisinin
      piperaquine and artemether-lumefantrine. Healthy volunteers of either sex aged 18
      to 65 years without glucose-6-phosphate dehydrogenase deficiency were randomized
      into five cohorts (n = 24 per cohort) to receive tafenoquine on day 1 (300 mg)
      plus once-daily dihydroartemisinin-piperaquine on days 1, 2, and 3 (120 mg/960 mg
      for 36 to <75 kg of body weight and 160 mg/1,280 mg for >=75 to 100 kg of body
      weight), or plus artemether-lumefantrine (80 mg/480 mg) in two doses 8 h apart on
      day 1 and then twice daily on days 2 and 3, or each drug alone. The
      pharmacokinetic parameters of tafenoquine, piperaquine, lumefantrine, artemether,
      and dihydroartemisinin were determined by using noncompartmental methods. Point
      estimates and 90% confidence intervals were calculated for area under the
      concentration-time curve (AUC) and maximum observed plasma concentration (Cmax)
      comparisons of tafenoquine plus ACT versus tafenoquine or ACT. All subjects
      receiving dihydroartemisinin-piperaquine experienced QTc prolongation (a known
      risk with this drug), but tafenoquine coadministration had no clinically relevant
      additional effect. Tafenoquine coadministration had no clinically relevant
      effects on dihydroartemisinin, piperaquine, artemether, or lumefantrine
      pharmacokinetics. Dihydroartemisinin-piperaquine coadministration increased the
      tafenoquine Cmax by 38% (90% confidence interval, 25 to 52%), the AUC from time
      zero to infinity (AUC0-infinity) by 12% (1 to 26%), and the half-life (t1/2) by
      29% (19 to 40%), with no effect on the AUC from time zero to the time of the last
      nonzero concentration (AUC0-last). Artemether-lumefantrine coadministration had
      no effect on tafenoquine pharmacokinetics. Tafenoquine can be coadministered with
      dihydroartemisinin-piperaquine or artemether-lumefantrine without dose adjustment
      for any of these compounds. (This study has been registered at ClinicalTrials.gov
      under registration no. NCT02184637.).

PMID- 27697759
TI  - Risk Factors, Outcomes, and Mechanisms of Tigecycline-Nonsusceptible Klebsiella
      pneumoniae Bacteremia.
AB  - A rise in tigecycline resistance in Klebsiella pneumoniae has been reported
      recently worldwide. We sought to identify risk factors, outcomes, and mechanisms
      for adult patients with tigecycline-nonsusceptible K. pneumoniae bacteremia in
      Taiwan. We conducted a matched case-control study (ratio of 1:1) in a medical
      center in Taiwan from January 2011 through June 2015. The cases were patients
      with tigecycline-nonsusceptible K. pneumoniae bacteremia, and the controls were
      patients with tigecycline-susceptible K. pneumoniae bacteremia. Logistic
      regression was performed to evaluate the potential risk factors for tigecycline
      nonsusceptible K. pneumoniae bacteremia. Quantitative reverse transcription-PCR
      was performed to analyze acrA, oqxA, ramA, rarA, and kpgA expression among these
      isolates. A total of 43 cases were matched with 43 controls. The 14-day mortality
      of patients with tigecycline-nonsusceptible K. pneumoniae bacteremia was 30.2%,
      and the 28-day mortality was 41.9%. The attributable mortalities of tigecycline
      nonsusceptible K. pneumoniae at 14 and 28 days were 9.3 and 18.6%, respectively.
      Fluoroquinolone use within 30 days prior to bacteremia was the only independent
      risk factor for tigecycline-nonsusceptible K. pneumoniae bacteremia. The
      tigecycline-nonsusceptible K. pneumoniae bacteremia was mostly caused by
      overexpression of AcrAB and/or OqxAB efflux pumps, together with the upregulation
      of RamA and/or RarA, respectively. One isolate demonstrated isolated
      overexpression of kpgA In conclusion, tigecycline-nonsusceptible K. pneumoniae
      bacteremia was associated with high mortality, and prior fluoroquinolone use was
      the independent risk factor for the acquisition of tigecycline-nonsusceptible K.
      pneumoniae The overexpression of AcrAB and/or OqxAB contributes to tigecycline
      nonsusceptibility in K. pneumoniae.

PMID- 27697760
TI  - Pharmacokinetics of the Antischistosomal Lead Ozonide OZ418 in Uninfected Mice
      Determined by Liquid Chromatography-Tandem Mass Spectrometry.
AB  - One of the major neglected tropical diseases, schistosomiasis, is currently
      treated and controlled with a single drug, praziquantel. The quest for an
      alternative drug is fueled by the lack of activity of praziquantel against
      juvenile Schistosoma worms and the fear of emerging resistance. The synthetic
      ozonide OZ418 has shown high activity against Schistosoma mansoni, S.
      haematobium, and S. japonicum in vivo, but its drug disposition remains unknown.
      To bridge this gap, our study determined the basic pharmacokinetic (PK)
      parameters of a single oral dose (400 mg/kg of body weight) of OZ418 in
      uninfected mice. First, a simple liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method to quantify OZ418 concentrations in mouse plasma was
      successfully developed and validated according to U.S. FDA guidelines. This
      method proved to be selective, accurate (93 to 103%), precise (5 to 16%), and
      devoid of significant matrix effects (90 to 102%) and provided excellent recovery
      (101 to 102%). A median peak concentration of 190 (range, 185 to 231) MUg/ml was
      reached at 2 h (2 to 3 h) posttreatment. A naive pooled noncompartmental PK
      analysis estimated a mean area under the plasma concentration-versus-time curve
      (AUC) of 9,303 MUg h/ml (7,039.2 to 11,908.5 MUg h/ml) and a half-life of 38.7 h
      (20 to 64.6 h). Thus, the OZ418 level in plasma remained well above its in vitro
      50% inhibitory concentrations (IC50s) of 27.4 MUg/ml (adult S. mansoni worms at
      72 h) for at least 75 h. Consistently, OZ418 degraded little in plasma at 37
      degrees C (<20% in 121 h) and weakly inhibited cytochrome P450 (CYP450)
      metabolism (IC50 of 37 to 144 MUM). Our results provide a first insight into the
      disposition of OZ418, paving the way for further studies of its biological fate
      and effect.

PMID- 27697761
TI  - High-Dose Micafungin for Preterm Neonates and Infants with Invasive and Central
      Nervous System Candidiasis.
AB  - High doses of micafungin are advocated in neonates with systemic candidiasis, but
      limited pharmacokinetic (PK) and safety data are available to support their use.
      Eighteen preterm neonates and infants with systemic candidiasis, three of whom
      had meningitis, were treated for at least 14 days with 8 to 15 mg/kg of body
      weight/day of intravenous micafungin. Plasma micafungin concentrations (four
      measurements for each patient) were determined after the third dose, and the
      cerebrospinal fluid (CSF) micafungin concentrations in three patients were also
      obtained. Population PK analyses were used to identify the optimal model, and the
      model was further validated using external data (n = 5). The safety of micafungin
      was assessed by measurement of the levels of liver and kidney function
      biomarkers. The mean age and weight at the initiation of treatment were 2.33
      months (standard deviation [SD], 1.98 months) and 3.24 kg (SD, 1.61 kg),
      respectively. The optimal PK model was one that scaled plasma clearance to weight
      and the transaminase concentration ratio. The CSF of three patients was sampled,
      and the observed concentrations were between 0.80 and 1.80 mg/liter. The model
      predicted mean micafungin area under the concentration-time curve over 24 h was
      336 mg . h/liter (SD, 165 mg . h/liter) with the 10-mg/kg/day dosage. Eighteen of
      the 23 subjects (78.2%) had clinical resolution of their infection, but 5 had
      neurologic impairments. Among the transaminases, alkaline phosphatase
      measurements were significantly higher posttreatment, with a geometric mean ratio
      of 1.17 (90% confidence interval, 1.01, 1.37). Furthermore, marked elevations in
      the gamma-glutamyltransferase (GGT) level were observed in three patients treated
      with 10- to 15-mg/kg/day doses, and improvement of the GGT level was noted after
      a dose reduction. Higher weight-based doses of micafungin were generally well
      tolerated in neonates and infants and achieved pharmacokinetic profiles
      predictive of an effect.

PMID- 27697763
TI  - A Single Nucleotide Change in the Promoter mutp Enhances Fluoride Resistance of
      Streptococcus mutans.
AB  - Previously, we identified a single nucleotide mutation in the promoter (mutp) of
      the fluoride antiporter-coding genes in a naturally fluoride-resistant
      Streptococcus mutans strain. Here, we studied the role of this mutation in a
      defined genetic background. The results confirmed that this mutation alone
      confers fluoride resistance on S. mutans, as shown by growth and lactic acid
      production assays. This resistance was explained by constitutively higher mutp
      promoter activity and upregulation of the fluoride antiporter-coding genes.

PMID- 27697762
TI  - Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised
      Children.
AB  - Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive
      fungal disease (IFD) in adults and children. There are relatively limited
      pharmacokinetic (PK) data to inform optimal dosing in children that achieves
      systemic drug exposures comparable to those of adults. Our objective was to
      describe the pharmacokinetics of LAmB in children aged 1 to 17 years with
      suspected or documented IFD. Thirty-five children were treated with LAmB at doses
      of 2.5 to 10 mg kg-1 daily. Samples were taken at baseline and at 0.5- to 2.0-h
      intervals for 24 h after receipt of the first dose (n = 35 patients) and on the
      final day of therapy (n = 25 patients). LAmB was measured using high-performance
      liquid chromatography (HPLC). The relationship between drug exposure and
      development of toxicity was explored. An evolution in PK was observed during the
      course of therapy, resulting in a proportion of patients (n = 13) having
      significantly higher maximum serum concentrations (Cmax) and areas under the
      concentration-time curve from 0 to 24 h (AUC0-24) later in the course of therapy,
      without evidence of drug accumulation (trough plasma concentration accumulation
      ratio of <1.2). The fit of a 2-compartment model incorporating weight and an
      exponential decay function describing volume of distribution best described the
      data. There was a statistically significant relationship between mean AUC0-24 and
      probability of nephrotoxicity (odds ratio, 2.37; 95% confidence interval, 1.84 to
      3.22; P = 0.004). LAmB exhibits nonlinear pharmacokinetics. A third of children
      appear to experience a time-dependent change in PK, which is not explained by
      weight, maturation, or observed clinical factors.

PMID- 27697764
TI  - Breaking the Permeability Barrier of Escherichia coli by Controlled
      Hyperporination of the Outer Membrane.
AB  - In Gram-negative bacteria, a synergistic relationship between slow passive uptake
      of antibiotics across the outer membrane and active efflux transporters creates a
      permeability barrier, which efficiently reduces the effective concentrations of
      antibiotics in cells and, hence, their activities. To analyze the relative
      contributions of active efflux and the passive barrier to the activities of
      antibiotics, we constructed Escherichia coli strains with controllable
      permeability of the outer membrane. The strains expressed a large pore that does
      not discriminate between compounds on the basis of their hydrophilicity and
      sensitizes cells to a variety of antibacterial agents. We found that the
      efficacies of antibiotics in these strains were specifically affected by either
      active efflux or slow uptake, or both, and reflect differences in the properties
      of the outer membrane barrier, the repertoire of efflux pumps, and the inhibitory
      activities of antibiotics. Our results identify antibiotics which are the best
      candidates for the potentiation of activities through efflux inhibition and
      permeabilization of the outer membrane.

PMID- 27697765
TI  - EULAR recommendations for cardiovascular disease risk management in patients with
      rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016
      update.
AB  - Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders
      (IJD) have increased cardiovascular disease (CVD) risk compared with the general
      population. In 2009, the European League Against Rheumatism (EULAR) taskforce
      recommended screening, identification of CVD risk factors and CVD risk management
      largely based on expert opinion. In view of substantial new evidence, an update
      was conducted with the aim of producing CVD risk management recommendations for
      patients with IJD that now incorporates an increasing evidence base. A
      multidisciplinary steering committee (representing 13 European countries)
      comprised 26 members including patient representatives, rheumatologists,
      cardiologists, internists, epidemiologists, a health professional and fellows.
      Systematic literature searches were performed and evidence was categorised
      according to standard guidelines. The evidence was discussed and summarised by
      the experts in the course of a consensus finding and voting process. Three
      overarching principles were defined. First, there is a higher risk for CVD in
      patients with RA, and this may also apply to ankylosing spondylitis and psoriatic
      arthritis. Second, the rheumatologist is responsible for CVD risk management in
      patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and
      corticosteroids should be in accordance with treatment-specific recommendations
      from EULAR and Assessment of Spondyloarthritis International Society. Ten
      recommendations were defined, of which one is new and six were changed compared
      with the 2009 recommendations. Each designated an appropriate evidence support
      level. The present update extends on the evidence that CVD risk in the whole
      spectrum of IJD is increased. This underscores the need for CVD risk management
      in these patients. These recommendations are defined to provide assistance in CVD
      risk management in IJD, based on expert opinion and scientific evidence.

PMID- 27697766
TI  - EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance.
AB  - The lack of effective tumor-associated antigens restricts the development of
      targeted therapies against myeloid leukemia. In this study, we compared gene
      expression patterns of acute myeloid leukemia (AML) and normal bone marrow
      samples and found that epithelial cell adhesion molecule (EpCAM) is frequently
      overexpressed in patients with AML, with EpCAM+ leukemic cells exhibiting
      enhanced chemoresistance and oncogenesis. The chemotherapeutic resistance of
      EpCAM-positive leukemic cells is a consequence of increased WNT5B signaling.
      Furthermore, we generated EpCAM antibodies that enabled phagocytosis or
      cytotoxicity of AML cells by macrophage or natural killer cells, respectively.
      Finally, EpCAM antibody treatment depleted AML in subcutaneous, disseminated, and
      intramedullary engrafted mice. In summary, EpCAM exhibits promise as a novel
      target for the treatment of leukemia. Cancer Res; 77(2); 482-93. (c)2016 AACR.

PMID- 27697767
TI  - Lurbinectedin Inactivates the Ewing Sarcoma Oncoprotein EWS-FLI1 by
      Redistributing It within the Nucleus.
AB  - There is a great need to develop novel approaches to target oncogenic
      transcription factors with small molecules. Ewing sarcoma is emblematic of this
      need, as it depends on the continued activity of the EWS-FLI1 transcription
      factor to maintain the malignant phenotype. We have previously shown that the
      small molecule trabectedin interferes with EWS-FLI1. Here, we report important
      mechanistic advances and a second-generation inhibitor to provide insight into
      the therapeutic targeting of EWS-FLI1. We discovered that trabectedin
      functionally inactivated EWS-FLI1 by redistributing the protein within the
      nucleus to the nucleolus. This effect was rooted in the wild-type functions of
      the EWSR1, compromising the N-terminal half of the chimeric oncoprotein, which is
      known to be similarly redistributed within the nucleus in the presence of UV
      light damage. A second-generation trabectedin analogue lurbinectedin (PM01183)
      caused the same nuclear redistribution of EWS-FLI1, leading to a loss of activity
      at the promoter, mRNA, and protein levels of expression. Tumor xenograft studies
      confirmed this effect, and it was increased in combination with irinotecan,
      leading to tumor regression and replacement of Ewing sarcoma cells with benign
      fat cells. The net result of combined lurbinectedin and irinotecan treatment was
      a complete reversal of EWS-FLI1 activity and elimination of established tumors in
      30% to 70% of mice after only 11 days of therapy. Our results illustrate the
      preclinical safety and efficacy of a disease-specific therapy targeting the
      central oncogenic driver in Ewing sarcoma. Cancer Res; 76(22); 6657-68. (c)2016
      AACR.

PMID- 27697768
TI  - Therapeutic effects of dry needling in patients with upper trapezius myofascial
      trigger points.
AB  - BACKGROUND: Active myofascial trigger points (MTrPs) are major pain generators in
      myofascial pain syndrome. Dry needling (DN) is an effective method for the
      treatment of MTrPs. OBJECTIVE: To assess the immediate neurophysiological and
      clinical effects of DN in patients with upper trapezius MTrPs. METHODS: This was
      a prospective, clinical trial study of 20 patients with upper trapezius MTrPs and
      20 healthy volunteers (matched for height, weight, body mass index and age), all
      of whom received one session of DN. Primary outcome measures were neuromuscular
      junction response (NMJR) and sympathetic skin response (SSR). Secondary outcomes
      were pain intensity (PI) and pressure pain threshold (PPT). Data were collected
      at baseline and immediately post-intervention. RESULTS: At baseline, SSR
      amplitude was higher in patients versus healthy volunteers (p<0.003). With
      respect to NMJR, a clinically abnormal increment and normal reduction was
      observed in patients and healthy volunteers, respectively. Moreover, PPT of
      patients was less than healthy volunteers (p<0.0001). After DN, SSR amplitude
      decreased significantly in patients (p<0.01), but did not change in healthy
      volunteers. A clinically important reduction in the NMJR of patients and
      increment in healthy volunteers was demonstrated after DN. PPT increased after DN
      in patients, but decreased in healthy volunteers (p<0.0001). PI improved after DN
      in patients (p<0.001). CONCLUSIONS: The results of this study showed that one
      session of DN targeting active MTrPs appears to reduce hyperactivity of the
      sympathetic nervous system and irritability of the motor endplate. DN seems
      effective at improving symptoms and deactivating active MTrPs, although further
      research is needed. TRIAL REGISTRATION NUMBER: IRCT20130316128.

PMID- 27697769
TI  - Effects of myofascial trigger point dry needling in patients with sleep bruxism
      and temporomandibular disorders: a prospective case series.
AB  - OBJECTIVES: To investigate the effects of deep dry needling (DN) of myofascial
      trigger points (MTrPs) of the masseter and temporalis on pain, pressure pain
      threshold (PPT), pain-free maximal jaw opening and temporomandibular disorder
      (TMD)-related disability in patients with sleep bruxism (SB) and myofascial TMD.
      METHODS: Seventeen subjects (11 women, 6 men) aged 39+/-13 years (range 23-66)
      diagnosed with SB and myofascial TMD were invited to participate in this
      prospective case series study. Each subject received a deep DN intervention in
      the masseter and temporalis MTrPs. Pain intensity, PPT, pain-free maximal jaw
      opening and TMD-related disability were assessed before treatment, immediately
      after treatment and at 1-week follow-up. Jaw disability was assessed using the
      jaw disability checklist (JDC) at baseline and 1 week post-treatment only.
      RESULTS: One-way analyses of variance showed significant improvements in pain
      intensity, PPT and jaw opening (p<0.001). Post-hoc analysis revealed significant
      differences between baseline and post-intervention follow-up time points in pain
      (immediate: Cohen's d=1.72, p<0.001; 1 week: d=3.24, p<0.001), jaw opening
      (immediate: d=0.77, p<0.001; 1 week: d=1.02, p<0.001) and PPT in the masseter
      (immediate: d=1.02, p<0.001; 1 week: d=1.64, p<0.001) and temporalis (immediate:
      d=0.91, p=0.006; 1 week: d=1.8, p<0.001). A dependent t-test showed a significant
      improvement in jaw functioning, reflected by a large reduction in 1-week JDC
      scores relative to baseline (d=3.15, p<0.001). CONCLUSIONS: Deep DN of active
      MTrPs in the masseter and temporalis in patients with myofascial TMD and SB was
      associated with immediate and 1-week improvements in pain, sensitivity, jaw
      opening and TMD-related disability. TRIAL REGISTRATION NUMBER: NCT02587182;
      Results.

PMID- 27697770
TI  - Minimal residual disease is an independent predictor for 10-year survival in CLL.
AB  - Minimal residual disease (MRD) negativity, defined as <1 chronic lymphocytic
      leukemia (CLL) cell detectable per 10 000 leukocytes, has been shown to
      independently predict for clinical outcome in patients receiving combination
      chemoimmunotherapy in the frontline setting. However, the long-term prognostic
      value of MRD status in other therapeutic settings remains unclear. Here, we
      retrospectively analyzed, with up to 18 years follow-up, all patients at our
      institution who achieved at least a partial response (PR) with various therapies
      between 1996 and 2007, and received a bone marrow MRD assessment at the end of
      treatment according to the international harmonized approach. MRD negativity
      correlated with both progression-free survival (PFS) and overall survival (OS)
      independent of the type and line of treatment, as well as known prognostic
      factors including adverse cytogenetics. The greatest impact of achieving MRD
      negativity was seen in patients receiving frontline treatment, with 10-year PFS
      of 65% vs 10% and 10-year OS of 70% vs 30% for MRD-negative vs MRD-positive
      patients, respectively. Our results demonstrate the long-term benefit of
      achieving MRD negativity, regardless of the therapeutic setting and treatment
      modality, and support its use as a prognostic marker for long-term PFS and as a
      potential therapeutic goal in CLL.

PMID- 27697771
TI  - Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated
      follicular lymphoma: Alliance A051103.
AB  - Chemoimmunotherapy in follicular lymphoma is associated with significant
      toxicity. Targeted therapies are being investigated as potentially more
      efficacious and tolerable alternatives for this multiply-relapsing disease. Based
      on promising activity with rituximab and lenalidomide in previously untreated
      follicular lymphoma (overall response rate [ORR] 90%-96%) and ibrutinib in
      relapsed disease (ORR 30%-55%), the Alliance for Clinical Trials in Oncology
      conducted a phase 1 trial of rituximab, lenalidomide, and ibrutinib. Previously
      untreated patients with follicular lymphoma received rituximab 375 mg/m2 on days
      1, 8, 15, and 22 of cycle 1 and day 1 of cycles 4, 6, 8, and 10; lenalidomide as
      per cohort dose on days 1 to 21 of 28 for 18 cycles; and ibrutinib as per cohort
      dose daily until progression. Dose escalation used a 3+3 design from a starting
      dose level (DL) of lenalidomide 15 mg and ibrutinib 420 mg (DL0) to DL2
      (lenalidomide 20 mg, ibrutinib 560 mg). Twenty-two patients were enrolled; DL2
      was determined to be the recommended phase II dose. Although no protocol-defined
      dose-limiting toxicities were reported, a high incidence of rash was observed
      (all grades 82%, grade 3 36%). Eleven patients (50%) required dose reduction, 7
      because of rash. The ORR for the entire cohort was 95%, and the 12-month
      progression-free survival was 80% (95% confidence interval, 57%-92%). Five
      patients developed new malignancies; 3 had known risk factors before enrollment.
      Given the increased toxicity and required dose modifications, as well as the
      apparent lack of additional clinical benefit to the rituximab-lenalidomide
      doublet, further investigation of the regimen in this setting seems unwarranted.
      The study was registered with www.ClinicalTrials.gov as #NCT01829568.

PMID- 27697772
TI  - Rational targeted therapies to overcome microenvironment-dependent expansion of
      mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) accumulates in lymphoid organs, but disseminates early
      on in extranodal tissues. Although proliferation remains located in lymphoid
      organs only, suggesting a major role of the tumor ecosystem, few studies have
      assessed MCL microenvironment. We therefore cocultured primary circulating MCL
      cells from 21 patients several weeks ex vivo with stromal or lymphoid-like
      (CD40L) cells to determine which interactions could support their proliferation.
      We showed that coculture with lymphoid-like cells, but not stromal cells, induced
      cell-cycle progression, which was amplified by MCL-specific cytokines (insulin
      like growth factor-1, B-cell activating factor, interleukin-6, interleukin-10).
      Of interest, we showed that our model recapitulated the MCL in situ molecular
      signatures (ie, proliferation, NF-kappaB, and survival signatures). We further
      demonstrated that proliferating MCL harbored an imbalance in Bcl-2 family
      expression, leading to a consequent loss of mitochondrial priming. Of interest,
      this loss of priming was overcome by the type II anti-CD20 antibody obinutuzumab,
      which counteracted Bcl-xL induction through NF-kappaB inhibition. Finally, we
      showed that the mitochondrial priming directly correlated with the sensitivity
      toward venetoclax and alkylating drugs. By identifying the microenvironment as
      the major support for proliferation and drug resistance in MCL, our results
      highlight a selective approach to target the lymphoma niche.

PMID- 27697773
TI  - High incidence of activating STAT5B mutations in CD4-positive T-cell large
      granular lymphocyte leukemia.

PMID- 27697774
TI  - Haploidentical hematopoietic transplantation for the cure of leukemia: from its
      biology to clinical translation.
AB  - The present review describes the biology of human leukocyte antigen haplotype
      mismatched ("haploidentical") transplantation, its translation to clinical
      practice to cure leukemia, and the results of current transplantation protocols.
      The 1990s saw what had been major drawbacks of haploidentical transplantation,
      ie, very strong host-versus-graft and graft-versus-host alloresponses, which led
      respectively to rejection and graft-versus-host disease (GVHD), being overcome
      through transplantation of a "mega-dose" of T cell-depleted peripheral blood
      hematopoietic progenitor cells and no posttransplant pharmacologic
      immunosuppression. The absence of posttransplant immunosuppression was an
      opportunity to discover natural killer cell alloreactions that eradicated acute
      myeloid leukemia and improved survival. Furthermore, it also unveiled the
      benefits of transplantation from mother donors, a likely consequence of the
      mother-to-child interaction during pregnancy. More recent transplantation
      protocols use unmanipulated (without ex vivo T-cell depletion) haploidentical
      grafts combined with enhanced posttransplant immunosuppression to help prevent
      GVHD. Unmanipulated grafts substantially extended the use of haploidentical
      transplantation with results than even rival those of matched hematopoietic
      transplantation. In T cell-depleted haploidentical transplantation, recent
      advances were made by the adoptive transfer of regulatory and conventional T
      cells.

PMID- 27697775
TI  - Strategies before, during, and after hematopoietic cell transplantation to
      improve T-cell immune reconstitution.
AB  - T-cell immune reconstitution (IR) after allogeneic hematopoietic cell
      transplantation (allo-HCT) is highly variable between patients and may take
      several months to even years. Patients with delayed or unbalanced T-cell IR have
      a higher probability of developing transplantation-related morbidity, mortality,
      and relapse of disease. Hence, there is a need for strategies to better predict
      and improve IR to reduce these limitations of allo-HCT. In this review, we
      provide an update of current and in-near-future clinically relevant strategies
      before, during, and after transplantation to achieve successful T-cell IR. Potent
      strategies are choosing the right HCT source (eg, donor-recipient matching, cell
      dose, graft manipulation), individualized conditioning and serotherapy (eg,
      antithymocyte globulin), nutritional status, exercise, home care, modulation of
      microbiota, enhancing homeostatic peripheral expansion, promoting thymopoiesis,
      and the use of adjuvant-targeted cellular immunotherapies. Strategies to prevent
      graft-versus-host disease are important as well because this complication and the
      subsequent need for immunosuppression affects T-cell IR and function. These
      options aim for personalized precision transplantation, where allo-HCT therapy is
      designed to boost a well-balanced T-cell IR and limit complications in individual
      patients, resulting in overall lower morbidity and higher survival chances.

PMID- 27697776
TI  - AACR Cancer Progress Report 2016.

PMID- 27697777
TI  - Implication of external price referencing and parallel trade on pharmaceutical
      expenditure: indirect evidence from lower-income European countries.
AB  - External price referencing (EPR) is applied more and more frequently worldwide by
      payers to control pharmaceutical prices. Together with the parallel trade of
      pharmaceuticals, EPR may result in lower pharmaceutical prices in higher-income
      countries and higher prices in lower-income countries, which implies that
      pharmaceutical expenditure grows more rapidly in the latter than in the former
      group. Our objective was to assess this hypothesis. We used hierarchical linear
      models on country-level panel data to show that-after controlling for compounding
      factors such as GDP, the proportion of the old-age population or life expectancy
      the annual growth rate of pharmaceutical expenditure was 2.1% points larger in
      the lower- than in the higher-income members of the European Union between 2000
      and 2008. This difference in trends became non-significant (0.6% points) after
      the onset of the global economic crisis. There was no significant difference
      between lower- and higher-income countries in the growth rate of non
      pharmaceutical health expenditure in either period. Our results indirectly
      support the presence of price convergence of pharmaceuticals among European
      countries, and EPR and parallel trade may provide a reasonable explanation to the
      observed trend difference of pharmaceutical expenditure in the two groups of
      countries between 2000 and 2008. This higher growth rate of pharmaceutical
      expenditure put extra burden on public health care budgets in lower-income
      countries and resulted in disproportionately more cost-containment measures
      compared to higher-income countries after 2008. It remains to be seen whether the
      disappearance of the difference in trend growth rates due to special health
      policy interventions in countries with economic difficulties is temporary or
      permanent.

PMID- 27697778
TI  - Aquatic Habits of Cetacean Ancestors: Integrating Bone Microanatomy and Stable
      Isotopes.
AB  - The earliest cetaceans were interpreted as semi-aquatic based on the presence of
      thickened bones and stable oxygen isotopes in tooth enamel. However, the origin
      of aquatic behaviors in cetacean relatives (e.g., raoellids, anthracotheres)
      remains unclear. This study reconstructs the origins of aquatic behaviors based
      on long bone microanatomy and stable oxygen isotopes of tooth enamel in modern
      and extinct cetartiodactylans. Our findings are congruent with published accounts
      that microanatomy can be a reliable indicator of aquatic behaviors in taxa that
      are obligatorily aquatic, and also highlight that some "semi-aquatic" behaviors
      (fleeing into the water to escape predation) may have a stronger relationship to
      bone microanatomy than others (herbivory in near-shore aquatic settings). Bone
      microanatomy is best considered with other lines of information in the land-to
      sea transition of cetaceans, such as stable isotopes. This study extends our
      understanding of the progression of skeletal phenotypes associated with habitat
      shifts in the relatives of cetaceans.

PMID- 27697779
TI  - Secondary Evolution of Aquatic Propulsion in Higher Vertebrates: Validation and
      Prospect.
AB  - Re-invasion of the aquatic environment by terrestrial vertebrates resulted in the
      evolution of species expressing a suite of adaptations for high-performance
      swimming. Examination of swimming by secondarily aquatic vertebrates provides
      opportunities to understand potential selection pressures and mechanical
      constraints, which may have directed the evolution of these aquatic species.
      Mammals and birds realigned the body and limbs for cursorial movements and
      flight, respectively, from the primitive tetrapod configuration. This realignment
      produced multiple solutions for aquatic specializations and swimming modes.
      Initially, in the evolution of aquatic mammals and birds, swimming was
      accomplished by using paired appendages in a low-efficiency, drag-based paddling
      mode. This mode of swimming arose from the modification of neuromotor patterns
      associated with gaits characteristic of terrestrial and aerial locomotion. The
      evolution of advanced swimming modes occurred in concert with changes in buoyancy
      control for submerged swimming, and a need for increased aquatic performance.
      Aquatic mammals evolved three specialized lift-based modes of swimming that
      included caudal oscillation, pectoral oscillation, and pelvic oscillation. Based
      on modern analogs, a biomechanical model was developed to explain the evolution
      of specialized aquatic mammals and their transitional forms. Subsequently, fossil
      aquatic mammals were described that validated much of the model. However, for
      birds, which were adapted for aerial flight, fossil evidence has been less
      forthcoming to explain the transition to aquatic capabilities. A biomechanical
      model is proposed for birds to describe the evolution of specialized lift-based
      foot and wing swimming. For both birds and mammals, convergence in morphology and
      propulsive mechanics is dictated by the need to increase speed, reduce drag,
      improve thrust output, enhance efficiency, and control maneuverability in the
      aquatic environment.

PMID- 27697781
TI  - Asymptomatic Intradialytic Supraventricular Arrhythmias and Adverse Outcomes in
      Patients on Hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Supraventricular arrhythmias are associated with high
      morbidity and mortality. Nevertheless, this condition has received little
      attention in patients on hemodialysis. The objective of this study was to analyze
      the incidence of intradialysis supraventricular arrhythmia and its long-term
      prognostic value. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We designed an
      observational and prospective study in a cohort of patients on hemodialysis with
      a 10-year follow-up period. All patients were recruited for study participation
      and were not recruited for clinical indications. The study population comprised
      77 patients (42 men and 35 women; mean age =58+/-15 years old) with sinus rhythm
      monitored using a Holter electrocardiogram over six consecutive hemodialysis
      sessions at recruitment. RESULTS: Hypertension was present in 68.8% of patients,
      and diabetes was present in 29.9% of patients. Supraventricular arrhythmias were
      recorded in 38 patients (49.3%); all of these were short, asymptomatic, and self
      limiting. Age (hazard ratio, 1.04 per year; 95% confidence interval, 1.00 to
      1.08) and right atrial enlargement (hazard ratio, 4.29; 95% confidence interval,
      1.30 to 14.09) were associated with supraventricular arrhythmia in the
      multivariate analysis. During a median follow-up of 40 months, 57 patients died,
      and cardiovascular disease was the main cause of death (52.6%). The variables
      associated with all-cause mortality in the Cox model were age (hazard ratio, 1.04
      per year; 95% confidence interval, 1.00 to 1.08), C-reactive protein (hazard
      ratio, 1.04 per 1 mg/L; 95% confidence interval, 1.00 to 1.08), and
      supraventricular arrhythmia (hazard ratio, 3.21; 95% confidence interval, 1.29 to
      7.96). Patients with supraventricular arrhythmia also had a higher risk of
      nonfatal cardiovascular events (hazard ratio, 4.32; 95% confidence interval, 2.11
      to 8.83) and symptomatic atrial fibrillation during follow-up (hazard ratio,
      17.19; 95% confidence interval, 2.03 to 145.15). CONCLUSIONS: The incidence of
      intradialysis supraventricular arrhythmia was high in our hemodialysis study
      population. Supraventricular arrhythmias were short, asymptomatic, and self
      limiting, and although silent, these arrhythmias were independently associated
      with mortality and cardiovascular events.

PMID- 27697782
TI  - Glomerular Pathology in Dent Disease and Its Association with Kidney Function.
AB  - BACKGROUND AND OBJECTIVES: Dent disease is a rare X-linked disorder characterized
      by low molecular weight proteinuria and often considered a renal tubular disease.
      However, glomerulosclerosis was recently reported in several patients. Thus, Dent
      disease renal histopathologic features were characterized and assessed, and their
      association with kidney function was assessed. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Clinical renal pathology reports and slides (where available) were
      collected from 30 boys and men in eight countries who had undergone clinical
      renal biopsy between 1995 and 2014. RESULTS: Median (25th, 75th percentiles) age
      at biopsy was 7.5 (5, 19) years with an eGFR of 69 (44, 94) ml/min per 1.73 m2
      and a 24-hour urine protein of 2000 (1325, 2936) mg. A repeat biopsy for steroid
      resistant proteinuria was performed in 13% (four of 30) of the patients.
      Prominent histologic findings included focal global glomerulosclerosis in 83% (25
      of 30; affecting 16%+/-19% glomeruli), mild segmental foot process effacement in
      57% (13 of 23), focal interstitial fibrosis in 60% (18 of 30), interstitial
      lymphocytic infiltration in 53% (16 of 30), and tubular damage in 70% (21 of 30).
      Higher percentages of globally sclerotic glomeruli, foot process effacement, and
      interstitial inflammation were associated with lower eGFR at biopsy, whereas foot
      process effacement was associated with steeper annual eGFR decline. CONCLUSIONS:
      These associations suggest a potential role for glomerular pathology,
      specifically involving the podocyte, in disease progression, which deserves
      further study. Furthermore, Dent disease should be suspected in boys and men who
      have unexplained proteinuria with focal global glomerulosclerosis and segmental
      foot process effacement on renal biopsy.

PMID- 27697783
TI  - Conservative Management and End-of-Life Care in an Australian Cohort with ESRD.
AB  - BACKGROUND AND OBJECTIVES: We aimed to determine the proportion of patients who
      switched to dialysis after confirmed plans for conservative care and compare
      survival and end-of-life care among patients choosing conservative care with
      those initiating RRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cohort
      study of 721 patients on incident dialysis, patients receiving transplants, and
      conservatively managed patients from 66 Australian renal units entered into the
      Patient Information about Options for Treatment Study from July 1 to September
      30, 2009 were followed for 3 years. A two-sided binomial test assessed the
      proportion of patients who switched from conservative care to RRT. Cox
      regression, stratified by center and adjusted for patient and treatment
      characteristics, estimated factors associated with 3-year survival. RESULTS: In
      total, 102 of 721 patients planned for conservative care, and median age was 80
      years old. Of these, 8% (95% confidence interval, 3% to 13%), switched to
      dialysis, predominantly for symptom management. Of 94 patients remaining on a
      conservative pathway, 18% were alive at 3 years. Of the total 721 patients, 247
      (34%) died by study end. In multivariable analysis, factors associated with all
      cause mortality included older age (hazard ratio, 1.55; 95% confidence interval,
      1.36 to 1.77), baseline serum albumin <3.0 versus 3.7-5.4 g/dl (hazard ratio,
      4.31; 95% confidence interval, 2.72 to 6.81), and management with conservative
      care compared with RRT (hazard ratio, 2.18; 95% confidence interval, 1.39 to
      3.40). Of 247 deaths, patients managed with RRT were less likely to receive
      specialist palliative care (26% versus 57%; P<0.001), more likely to die in the
      hospital (66% versus 42%; P<0.001) than home or hospice, and more likely to
      receive palliative care only within the last week of life (42% versus 15%;
      P<0.001) than those managed conservatively. CONCLUSIONS: Survival after 3 years
      of conservative management is common, with relatively few patients switching to
      dialysis. Specialist palliative care services are used more frequently and at an
      earlier time point for conservatively managed patients, a practice associated
      with better symptom management and quality of life.

PMID- 27697785
TI  - A flow cytometric method for estimating S-phase duration in plants.
AB  - The duration of the DNA synthesis stage (S phase) of the cell cycle is
      fundamental in our understanding of cell cycle kinetics, cell proliferation, and
      DNA replication timing programs. Most S-phase duration estimates that exist for
      plants are based on indirect measurements. We present a method for directly
      estimating S-phase duration by pulse-labeling root tips or actively dividing
      suspension cells with the halogenated thymidine analog 5-ethynl-2'-deoxyuridine
      (EdU) and analyzing the time course of replication with bivariate flow cytometry.
      The transition between G1 and G2 DNA contents can be followed by measuring the
      mean DNA content of EdU-labeled S-phase nuclei as a function of time after the
      labeling pulse. We applied this technique to intact root tips of maize (Zea mays
      L.), rice (Oryza sativa L.), barley (Hordeum vulgare L.), and wheat (Triticum
      aestivum L.), and to actively dividing cell cultures of Arabidopsis (Arabidopsis
      thaliana (L.) Heynh.) and rice. Estimates of S-phase duration in root tips were
      remarkably consistent, varying only by ~3-fold, although the genome sizes of the
      species analyzed varied >40-fold.

PMID- 27697780
TI  - The OncoArray Consortium: A Network for Understanding the Genetic Architecture of
      Common Cancers.
AB  - BACKGROUND: Common cancers develop through a multistep process often including
      inherited susceptibility. Collaboration among multiple institutions, and funding
      from multiple sources, has allowed the development of an inexpensive genotyping
      microarray, the OncoArray. The array includes a genome-wide backbone, comprising
      230,000 SNPs tagging most common genetic variants, together with dense mapping of
      known susceptibility regions, rare variants from sequencing experiments,
      pharmacogenetic markers, and cancer-related traits. METHODS: The OncoArray can be
      genotyped using a novel technology developed by Illumina to facilitate efficient
      genotyping. The consortium developed standard approaches for selecting SNPs for
      study, for quality control of markers, and for ancestry analysis. The array was
      genotyped at selected sites and with prespecified replicate samples to permit
      evaluation of genotyping accuracy among centers and by ethnic background.
      RESULTS: The OncoArray consortium genotyped 447,705 samples. A total of 494,763
      SNPs passed quality control steps with a sample success rate of 97% of the
      samples. Participating sites performed ancestry analysis using a common set of
      markers and a scoring algorithm based on principal components analysis.
      CONCLUSIONS: Results from these analyses will enable researchers to identify new
      susceptibility loci, perform fine-mapping of new or known loci associated with
      either single or multiple cancers, assess the degree of overlap in cancer
      causation and pleiotropic effects of loci that have been identified for disease
      specific risk, and jointly model genetic, environmental, and lifestyle-related
      exposures. IMPACT: Ongoing analyses will shed light on etiology and risk
      assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126
      35. (c)2016 AACR.

PMID- 27697786
TI  - Axillary buds are dwarfed shoots that tightly regulate GA pathway and GA
      inducible 1,3-beta-glucanase genes during branching in hybrid aspen.
AB  - Axillary buds (AXBs) of hybrid aspen (Populus tremula*P. tremuloides) contain a
      developing dwarfed shoot that becomes para-dormant at the bud maturation point.
      Para-dormant AXBs can grow out after stem decapitation, while dormant AXBs pre
      require long-term chilling to release them from dormancy. The latter is mediated
      by gibberellin (GA)-regulated 1,3-beta-glucanases, but it is unknown if GA is
      also important in the development, activation, and outgrowth of para-dormant
      AXBs. The present data show that para-dormant AXBs up-regulate GA receptor genes
      during their maturation, but curtail GA biosynthesis by down-regulating the rate
      limiting GIBBERELLIN 3-OXIDASE2 (GA3ox2), which is characteristically expressed
      in the growing apex. However, decapitation significantly up-regulated GA3ox2 and
      GA4-responsive 1,3-beta-glucanases (GH17-family; alpha-clade). In contrast,
      decapitation down-regulated gamma-clade 1,3-beta-glucanases, which were strongly
      up-regulated in maturing AXBs concomitant with lipid body accumulation.
      Overexpression of selected GH17 members in hybrid aspen resulted in
      characteristic branching patterns. The alpha-clade member induced an acropetal
      branching pattern, whereas the gamma-clade member activated AXBs in recurrent
      flushes during transient cessation of apex proliferation. The results support a
      model in which curtailing the final step in GA biosynthesis dwarfs the embryonic
      shoot, while high levels of GA precursors and GA receptors keep AXBs poised for
      growth. GA signaling, induced by decapitation, reinvigorates symplasmic supply
      routes through GA-inducible 1,3-beta-glucanases that hydrolyze callose at sieve
      plates and plasmodesmata.

PMID- 27697788
TI  - Challenges and perspectives in commercializing plastid transformation technology.
AB  - Plastid transformation has emerged as an alternative platform to generate
      transgenic plants. Attractive features of this technology include specific
      integration of transgenes-either individually or as operons-into the plastid
      genome through homologous recombination, the potential for high-level protein
      expression, and transgene containment because of the maternal inheritance of
      plastids. Several issues associated with nuclear transformation such as gene
      silencing, variable gene expression due to the Mendelian laws of inheritance, and
      epigenetic regulation have not been observed in the plastid genome. Plastid
      transformation has been successfully used for the production of therapeutics,
      vaccines, antigens, and commercial enzymes, and for engineering various agronomic
      traits including resistance to biotic and abiotic stresses. However, these
      demonstrations have usually focused on model systems such as tobacco, and the
      technology per se has not yet reached the market. Technical factors limiting this
      technology include the lack of efficient protocols for the transformation of
      cereals, poor transgene expression in non-green plastids, a limited number of
      selection markers, and the lengthy procedures required to recover fully
      segregated plants. This article discusses the technology of transforming the
      plastid genome, the positive and negative features compared with nuclear
      transformation, and the current challenges that need to be addressed for
      successful commercialization.

PMID- 27697787
TI  - Changes in the DNA methylation pattern of the host male gametophyte of viroid
      infected cucumber plants.
AB  - Eukaryotic organisms exposed to adverse conditions are required to show a certain
      degree of transcriptional plasticity in order to cope successfully with stress.
      Epigenetic regulation of the genome is a key regulatory mechanism allowing
      dynamic changes of the transcriptional status of the plant in response to stress.
      The Hop stunt viroid (HSVd) induces the demethylation of ribosomal RNA (rRNA) in
      cucumber (Cucumis sativus) leaves, leading to increasing transcription rates of
      rRNA. In addition to the clear alterations observed in vegetative tissues, HSVd
      infection is also associated with drastic changes in gametophyte development. To
      examine the basis of viroid-induced alterations in reproductive tissues, we
      analysed the cellular and molecular consequences of HSVd infection in the male
      gametophyte of cucumber plants. Our results indicate that in the pollen grain,
      accumulation of HSVd RNA induces a decondensation of the generative nucleus that
      correlates with a dynamic demethylation of repetitive regions in the cucumber
      genome that include rRNA genes and transposable elements (TEs). We therefore
      propose that HSVd infection impairs the epigenetic control of rRNA genes and TEs
      in gametic cells of cucumber, a phenomenon thus far unknown to occur in this
      reproductive tissue as a consequence of pathogen infection.

PMID- 27697790
TI  - Further clarity on cooperation and morality.
AB  - I explore the increasingly important issue of cooperation in immoral actions,
      particularly in connection with healthcare. Conscientious objection, especially
      as pertains to religious freedom in healthcare, has become a pressing issue in
      the light of the US Supreme Court judgement in Hobby Lobby Section 'Moral
      evaluation using the basic principles of cooperation' outlines a theory of
      cooperation inspired by Catholic moral theologians such as those cited by the
      court. The theory has independent plausibility and is at least worthy of serious
      consideration-in part because it is an instance of double-effect reasoning, which
      is also independently plausible despite its association with moral theology.
      Section 'Case study: Burwell v. Hobby Lobby' examines Hobby Lobby in detail. Even
      if the judgement was correct in that case the reasoning was not, as it involved
      applying a 'mere sincerity' test to the cooperation question. The mere sincerity
      test leads to absurd consequences, whereas a reasonableness test applied using
      the theory of cooperation defended here would avoid absurdity. Section 'A
      question of remoteness: "accommodations" and opt-outs' explores the post-Hobby
      Lobby problem further, examining opt-outs and accommodations: the Little Sisters
      of the Poor case shows how opt-outs are misunderstood on a mere sincerity test,
      which the court rightly rejected. Section 'Application to the medical field:
      Doogan and Wood' discusses the UK case of Doogan and Wood, concerning
      participation in abortion. Again, a judicially recognised ethic of cooperation,
      if it were part of the fabric of legal reasoning in such cases, would have
      enabled the conscientious objectors in this and similar situations to have their
      freedom of conscience and religion respected in a way that it currently is not.

PMID- 27697789
TI  - Spatial Regulation of ABCG25, an ABA Exporter, Is an Important Component of the
      Mechanism Controlling Cellular ABA Levels.
AB  - The phytohormone abscisic acid (ABA) plays crucial roles in various physiological
      processes, including responses to abiotic stresses, in plants. Recently, multiple
      ABA transporters were identified. The loss-of-function and gain-of-function
      mutants of these transporters show altered ABA sensitivity and stomata
      regulation, highlighting the importance of ABA transporters in ABA-mediated
      processes. However, how the activity of these transporters is regulated remains
      elusive. Here, we show that spatial regulation of ATP BINDING CASETTE G25
      (ABCG25), an ABA exporter, is an important mechanism controlling its activity.
      ABCG25, as a soluble green fluorescent protein (sGFP) fusion, was subject to
      posttranslational regulation via clathrin-dependent and adaptor protein complex-2
      dependent endocytosis followed by trafficking to the vacuole. The levels of
      sGFP:ABCG25 at the plasma membrane (PM) were regulated by abiotic stresses and
      exogenously applied ABA; PM-localized sGFP:ABCG25 decreased under abiotic stress
      conditions via activation of endocytosis in an ABA-independent manner, but
      increased upon application of exogenous ABA via activation of recycling from
      early endosomes in an ABA-dependent manner. Based on these findings, we propose
      that the spatial regulation of ABCG25 is an important component of the mechanism
      by which plants fine-tune cellular ABA levels according to cellular and
      environmental conditions.

PMID- 27697792
TI  - Cancer care in Romania: challenges and pitfalls of children's and adolescents'
      multifaceted involvement.
AB  - Communication about diagnosis and medical treatment for children suffering from
      life-threatening illnesses is complex. It is a primary step in involving underage
      patients and families in care and lays the foundation for obtaining parental
      permission and patient assent for treatment. In practice child participation in
      care is often difficult to obtain due to patients' different and sometimes
      fluctuating preferences, but also parents' protective strategies. Physicians may
      be susceptible to parental wishes to limit information and feel uncomfortable
      discussing issues related to uncertainty of cure with patients. A qualitative
      study in Romanian paediatric oncology units was conducted to explore children's
      involvement from the perspectives of parents and oncologists. Interviews with
      participants discussed 18 patient cases. Data were transcribed and thematic
      analysis was used to interpret and mine patients' involvement during treatment.
      Different facets of patient participation were identified: restricting, widening
      and enhancing involvement. A fourth category, unintentional involvement, occurred
      for all patients due to children's observations during long-term hospitalisations
      and access to Internet. Uncertainty overarched parental attitudes regarding the
      extent to which children should be included. Physicians usually complied with
      parental wishes to limit involvement, but together with parents involved patients
      at least in a practical way. Adults' protective attitude may backfire, as
      adolescents' online searches often expose patients to worse-case scenarios.
      Further research should acknowledge the hazards of restricted diagnosis
      disclosure and develop clinician tools to support families in communicating with
      patients. This should be paralleled by physician efforts to elicit patients'
      needs regarding participation.

PMID- 27697791
TI  - Victims, vectors and villains: are those who opt out of vaccination morally
      responsible for the deaths of others?
AB  - Mass vaccination has been a successful public health strategy for many contagious
      diseases. The immunity of the vaccinated also protects others who cannot be
      safely or effectively vaccinated-including infants and the immunosuppressed. When
      vaccination rates fall, diseases like measles can rapidly resurge in a
      population. Those who cannot be vaccinated for medical reasons are at the highest
      risk of severe disease and death. They thus may bear the burden of others'
      freedom to opt out of vaccination. It is often asked whether it is legitimate for
      states to adopt and enforce mandatory universal vaccination. Yet this neglects a
      related question: are those who opt out, where it is permitted, morally
      responsible when others are harmed or die as a result of their decision? In this
      article, we argue that individuals who opt out of vaccination are morally
      responsible for resultant harms to others. Using measles as our main example, we
      demonstrate the ways in which opting out of vaccination can result in a
      significant risk of harm and death to others, especially infants and the
      immunosuppressed. We argue that imposing these risks without good justification
      is blameworthy and examine ways of reaching a coherent understanding of
      individual moral responsibility for harms in the context of the collective action
      required for disease transmission. Finally, we consider several objections to
      this view, provide counterarguments and suggest morally permissible alternatives
      to mandatory universal vaccination including controlled infection, self-imposed
      social isolation and financial penalties for refusal to vaccinate.

PMID- 27697794
TI  - Body Powder and Ovarian Cancer Risk-What Is the Role of Recall Bias?

PMID- 27697795
TI  - Multilevel Small-Area Estimation of Multiple Cigarette Smoking Status Categories
      Using the 2012 Behavioral Risk Factor Surveillance System.
AB  - BACKGROUND: Smoking is the leading preventable cause of death; however, small
      area estimates for detailed smoking status are limited. We developed multilevel
      small-area estimate mixed models to generate county-level estimates for six
      smoking status categories: current, some days, every day, former, ever, and
      never. METHOD: Using 2012 Behavioral Risk Factor Surveillance System (BRFSS) data
      (our sample size = 405,233 persons), we constructed and fitted a series of
      multilevel logistic regression models and applied them to the U.S. Census
      population to generate county-level prevalence estimates. We mapped the estimates
      by sex and aggregated them into state and national estimates. We conducted
      comparisons for internal consistency with BRFSS states' estimates using Pearson
      correlation coefficients, and external validation with the 2012 National Health
      Interview Survey current smoking prevalence. RESULTS: Correlation coefficients
      ranged from 0.908 to 0.982, indicating high internal consistency. External
      validation indicated complete agreement (prevalence = 18.06%). We found large
      variations in current and former smoking status between and within states and by
      sex. County prevalence of former smokers was highest among men in the Northeast,
      North, and West. Utah consistently had the lowest smoking prevalence.
      CONCLUSIONS: Our models, which include demographic and geographic
      characteristics, provide reliable estimates that can be applied to multiple
      category outcomes and any demographic group. County and state estimates may help
      understand the variation in smoking prevalence in the United States and provide
      information for control and prevention. IMPACT: Detailed county and state smoking
      category estimates can help identify areas in need of tobacco control and
      prevention and potentially allow planning for health care. Cancer Epidemiol
      Biomarkers Prev; 25(10); 1402-10. (c)2016 AACR.

PMID- 27697796
TI  - Spatial Associations of Multiple Chronic Conditions Among Older Adults.
AB  - Multimorbidity, the presence of two or more chronic conditions in an individual,
      presents a major challenge for meeting the health care needs of older adults.
      This study advances understanding of multiple chronic conditions by using local
      colocation quotients to reveal spatial associations for five chronic conditions
      (arthritis, diabetes, heart disease, hypertension, and pulmonary disease) in a
      statewide panel of older adults in New Jersey. Among adults with three or more
      conditions, large concentrations of Arthritis-Heart Disease-Pulmonary Disease,
      Arthritis-Hypertension-Pulmonary Disease, and Diabetes-Heart Disease-Hypertension
      were observed, each triad located in different regions of the state. Individuals
      with other triads of conditions, in contrast, were distributed among all older
      adults in the sample as expected with no areas of local concentration. The study
      provides gerontologists with a new and effective method for uncovering
      geographical patterns in combinations of chronic conditions among the populations
      they serve, thereby enabling more effective interventions.

PMID- 27697797
TI  - Doing less with less.

PMID- 27697798
TI  - Rainbow medicine - supporting the needs of lesbian, gay, bisexual and trans
      patients.

PMID- 27697799
TI  - Audit of a tertiary heart failure outpatient service to assess compliance with
      NICE guidelines.
AB  - The National Institute for Health and Care Excellence (NICE) updated its
      guidelines for chronic heart failure (HF) in 2010. This re-audit assessed interim
      improvement as compared with an audit in 2011. Patients with HF (preserved and
      reduced ejection fraction) attending a tertiary cardiac centre over a 2-year
      period (January 2013-December 2014) were audited. The data collected included
      demographics, HF aetiology, medications, clinical parameters and cardiac
      rehabilitation. In total, 513 patients were audited. Compared with 2011, male
      preponderance (71%) and age (68+/-14 years, (Mean +/- SD)) were similar. 73% of
      patients lived outside of London. HF aetiologies included ischaemic heart disease
      (37% versus 40% in 2011), dilated cardiomyopathy (26% versus 20%) primary valve
      disease (13% versus 12%). For patients with left ventricular systolic dysfunction
      (n=434, 85% of patients audited) 89% were taking beta-blockers (compared with 77%
      in 2011), 91% an angiotensin converting enzyme inhibitor or angiotensin receptor
      blocker (86% in 2011) and 56% a mineralocorticoid receptor antagonist (44% in
      2011); 6% were prescribed ivabradine. All patients were reviewed at least 6
      monthly. Although 100% of patients were educated about exercise, only 21 (4%)
      enrolled in a supervised exercise programme. This audit demonstrated high rates
      of documentation, follow-up and compliance with guideline-based medical
      therapies. A consistent finding was poor access to cardiac rehabilitation.

PMID- 27697800
TI  - Iatrogenic Cushing's syndrome due to drug interaction between glucocorticoids and
      the ritonavir or cobicistat containing HIV therapies.
AB  - Ritonavir and cobicistat, used as pharmacokinetic enhancers in combination with
      some antiretrovirals (ARVs) for the treatment of HIV, are potent inhibitors of
      the CYP3A4 isoenzyme. Most glucocorticoids are metabolised via the CYP3A4 pathway
      and iatrogenic Cushing's syndrome (ICS), with possible secondary adrenal
      insufficiency (SAI), is a recognised complication following co-administration
      with ritonavir or cobicistat. A structured approach for identifying and managing
      potentially affected individuals has not been established.We systematically
      identified patients with ICS/SAI and found substantial heterogeneity in clinical
      practice across three large London HIV centres. While this significant drug
      interaction and its complications are now well-recognised, it is apparent that
      there is no standardised approach to management or guidance for the general
      physician. Here we describe the management of ICS/SAI in our current practice,
      review the available evidence and suggest practice recommendations.

PMID- 27697801
TI  - The effect of ivabradine on functional capacity in patients with chronic
      obstructive pulmonary disease.
AB  - Increased sympathetic tone and use of bronchodilators increase heart rate and
      this may worsen functional capacity in patients with chronic obstructive
      pulmonary disease (COPD). The aim of this study was to look at the short-term
      effect of the heart rate lowering drug ivabradine on clinical status in COPD
      patients.We randomised 80 COPD patients with sinus heart rate >=90 bpm into
      either taking ivabradine 7.5 mg twice per day or placebo for two weeks. We
      assessed all patients using the modified Borg scale and 6-minute walk test at
      baseline and then again 2 weeks after randomisation.There were no significant
      differences in age, sex, severity of airway obstruction (measured using forceful
      exhalation), severity of diastolic dysfunction or pulmonary artery systolic
      pressure between the two groups. The ivabradine group showed significant
      improvement in 6-minute walk distance (from 192.6+/-108.8 m at baseline to
      285.1+/-88.9 m at the end of the study) compared with the control group (230.6+/
      68.4 at baseline and 250.4+/-65.8 m at the end of study) (p<0.001). This
      improvement in the drug group was associated with significant improvement of
      dyspnea on modified Borg scale (p=0.007).Lowering heart rate with ivabradine can
      improve exercise capacity and functional class in COPD patients with resting
      heart rate >90 bpm.

PMID- 27697802
TI  - Stroke mimic diagnoses presenting to a hyperacute stroke unit.
AB  - Stroke services have been centralised in several countries in recent years.
      Diagnosing acute stroke is challenging and a high proportion of patients admitted
      to stroke units are diagnosed as a non-stroke condition (stroke mimics). This
      study aims to describe the stroke mimic patient group, including their impact on
      stroke services. We analysed routine clinical data from 2,305 consecutive
      admissions to a stroke unit at St George's Hospital, London. Mimic groupings were
      derived from 335 individual codes into 17 groupings. From 2,305 admissions, 555
      stroke mimic diagnoses were identified (24.2%) and 72% of stroke mimics had at
      least one stroke risk factor. Common mimic diagnoses were headache, seizure and
      syncope. Medically unexplained symptoms and decompensation of underlying
      conditions were also common. Median length of stay was 1 day; a diagnosis of
      dementia (p=0.028) or needing MRI (p=0.006) was associated with a longer stay.
      Despite emergency department assessment by specialist clinicians and computed
      tomography brain, one in four suspected stroke patients admitted to hospital had
      a non-stroke diagnosis. Stroke mimics represent a heterogeneous patient group
      with significant impacts on stroke services. Co-location of stroke and acute
      neurology services may offer advantages where service reorganisation is being
      considered.

PMID- 27697803
TI  - Where did the acute medical trainees go? A review of the career pathways of acute
      care common stem acute medical trainees in London.
AB  - Acute care common stem acute medicine (ACCS AM) training was designed to develop
      competent multi-skilled acute physicians to manage patients with multimorbidity
      from 'door to discharge' in an era of increasing acute hospital admissions.
      Recent surveys by the Royal College of Physicians have suggested that acute
      medical specialties are proving less attractive to trainees. However, data on the
      career pathways taken by trainees completing core acute medical training has been
      lacking. Using London as a region with a 100% fill rate for its ACCS AM training
      programme, this study showed only 14% of trainees go on to higher specialty
      training in acute internal medicine and a further 10% to pursue higher medical
      specialty training with dual accreditation with internal medicine. 16% of
      trainees switched from ACCS AM to emergency medicine or anaesthetics during core
      ACCS training, and intensive care medicine proved to be the most popular career
      choice for ACCS AM trainees (21%). The ACCS AM training programme therefore does
      not appear to be providing what it was set out to do and this paper discusses the
      potential causes and effects.

PMID- 27697804
TI  - Haemophagocytic lymphohistiocytosis: an elusive syndrome.
AB  - Haemophagocytic lymphohistiocytosis is a rare inflammatory condition. It can
      present in adult general medical patients and is a challenging diagnostic
      conundrum. This article provides an overview of the pathophysiology and clinical
      presentation of the syndrome for the general physician who will be rarely
      confronted with this problem but will have to act promptly when the situation
      arises. Treatment is also briefly discussed, although this usually occurs in a
      specialist setting after the diagnosis has been established.

PMID- 27697805
TI  - The health impacts of the refugee crisis: a medical charity perspective.
AB  - Over the last year, hundreds of thousands of refugees fleeing war and persecution
      have travelled from the Middle East to Europe. Arduous journeys and poor living
      conditions are causing myriad health problems and access to basic healthcare is
      extremely limited for those on the move. At every stage of the journey, people
      are suffering, including after they settle in Europe. The difficulty in managing
      non-communicable diseases means that some refugees are not getting the treatment
      they need, which in the long term can have a significant adverse impact on their
      health. Pregnant women are frequently unable to access antenatal care in Europe
      and the vaccination rate for refugee children is worrying low. Those who have
      suffered traumatic experiences in their home country are highly susceptible to
      developing psychological problems; an issue compounded by poverty, their
      displacement and being victims of violence.

PMID- 27697806
TI  - Drug therapies in type 2 diabetes: an era of personalised medicine.
AB  - Optimal management of diabetes involves a multidisciplinary approach.
      Prioritisation of lifestyle change, blood pressure and lipid control, and regular
      screening for complications are advocated in most international guidelines. Good
      glucose control, however, remains an important aim of treatment, although it is
      increasingly recognised that glucose targets should be individualised, with less
      stringent targets for older patients with significant comorbidities.In recent
      years, a number of newer therapies for hyperglycaemia have become available. This
      review aims to discuss currently available options for patients with type 2
      diabetes, and also discusses potential new therapies that may be on the horizon
      in the future.

PMID- 27697807
TI  - How to succeed as a junior doctor.
AB  - The Royal College of Physicians (RCP) organised an inaugural 1-day conference,
      the aim of which was to look into some of the key issues that junior doctors need
      to address when beginning their careers. The target audience was medical students
      but a few foundation doctors were also in attendance. The conference also helped
      to increase RCP engagement with medical students and foundation doctors. The day
      was co-chaired by Professor Kate Thomas (vice dean, University of Birmingham) and
      Dr Andrew Macleod and Dr Kanwaljit Sandhu (RCP regional advisors for the West
      Midlands).

PMID- 27697808
TI  - A new urticarial rash, diarrhoea and refractory hypotension in a man with a
      history of migraines.
AB  - We present the case of a man with a history of migraines treated with propanolol,
      referred with a rash, diarrhoea, vomiting and hypotension. Our case highlights
      how prior beta-blocker use may prolong anaphylaxis and cause refractory
      hypotension.

PMID- 27697809
TI  - An extreme case of platypnoea-orthodeoxia syndrome.
AB  - An 80-year-old female presented with progressive breathlessness, worse on sitting
      or standing and relieved by lying flat. Subsequent investigations identified a
      patent foramen ovale (PFO) with right-to-left flow across the interatrial septum
      (IAS). A diagnosis of platypnoea orthodeoxia syndrome secondary to inter-atrial
      shunting was made. Technical features precluded a percutaneous PFO closure so an
      open surgical repair was performed with complete resolution of symptoms. We
      discuss the pathophysiology and management of platypnoea orthodeoxia syndrome.

PMID- 27697810
TI  - Sarcopenia and frailty: new challenges for clinical practice.
AB  - Sarcopenia and frailty are important conditions that become increasingly
      prevalent with age. Sarcopenia is the loss of muscle mass and function, and
      frailty can be defined as multi-system impairment associated with increased
      vulnerability to stressors. There is overlap between the two conditions,
      especially in terms of the physical aspects of the frailty phenotype: low grip
      strength, gait speed and muscle mass. These measures have been associated with a
      wide range of ageing outcomes and can be assessed in the clinical setting. In
      terms of intervention, there is evidence for the benefit of resistance exercise
      programmes, although these may not always be feasible. Considerable research into
      the use of medicines, both existing and new, as well as dietary supplements is
      ongoing. Finally in order to prevent or delay the development of these
      conditions, an additional approach is to consider aetiological factors operating
      across the life course.

PMID- 27697811
TI  - Rational prescribing: the principles of drug selection.
AB  - Prescribing is the most important tool used by physicians to cure illness,
      relieve symptoms and prevent future disease. It is also a complex intellectual
      task that requires formulation of an appropriate treatment regimen from the many
      thousands available, taking into account the infinite variation in the patients
      they encounter. Unfortunately, the selection of a medicine and dosage regimen is
      sometimes suboptimal, leading to poor patient outcomes (eg treatment failure,
      avoidable adverse reactions). This article will highlight some of the common
      prescribing errors and will develop a rational approach that includes making a
      diagnosis, estimating prognosis, establishing the goals of therapy, selecting the
      most appropriate treatment and monitoring the effects of the treatment.

PMID- 27697812
TI  - The epidemiology of polypharmacy.
AB  - Polypharmacy describes, in simplistic terms, the use of multiple medications in
      an individual. It has become a normal aspect of modern medicine, driven by an
      ageing, multimorbid population, the increasing availability of preventative
      medications and an increasing use of single-disease guidelines and adherence to
      evidence-based practice. However, polypharmacy is also associated with a range of
      adverse outcomes, and is considered an important and increasing challenge for
      clinical practice. Here, we consider the definitions of polypharmacy, the extent
      and nature of medication use in different settings, and the type of problems
      encountered as a consequence of polypharmacy.

PMID- 27697813
TI  - The need for a prescribing competency framework to address the burden of complex
      polypharmacy among multiple long-term conditions.
AB  - The original requirement for a competency framework for prescribers was to
      identify the essential skills for non-medical prescribers. However, core
      prescribing competencies are relevant to any prescriber. The new, revised version
      is especially relevant for doctors/physicians. Doctors are the most frequent
      prescribers - prescribing is the most common therapeutic intervention. The
      quantity and complexity of medicine use is increasing through multiple treatment
      strategies/pathways for multiple comorbidities, resulting in polypharmacy -
      especially with long-term conditions. This is against a background of the ongoing
      introduction of new drugs with novel mechanisms of action with increased risks of
      adverse effects, compounded by drug-drug and disease-drug interactions. This has
      increased the need for monitoring and follow-up, including identification and
      management of poor adherence. It is challenging for doctors to maintain safe and
      effective prescribing and train other doctors and non-medical prescribers within
      the multidisciplinary team. The prescribing competency framework provides a
      systematic approach to support doctors to prescribe safely and effectively. It
      can be used by medical schools to teach prescribing, including preparation for
      the prescribing safety assessment; by F1/F2 doctors to support prescribing in
      early years; as part of prescribing quality improvement initiatives and as a
      continuing professional development framework in general practice or acute care
      settings.

PMID- 27697814
TI  - European drug market entries 2015 with new mechanisms of action.
AB  - In this article, we consider the new drugs approved for the European market in
      2015. We present a summary of the new mechanisms of action introduced and
      highlight three new mechanisms of action with a potentially high future impact:
      PCSK9 inhibition (alirocumab (Praluent(r)) and evolocumab (Repatha(r))) for
      hypercholesterolaemia, neprilysin inhibition (sacubitril in combination with
      valsartan (Entresto(r))) for heart failure, and interleukin-5 inhibition
      (mepolizumab (Nucala(r))) for asthma.

PMID- 27697815
TI  - Adverse drug reactions.
AB  - Adverse drug reactions (ADRs) remain a challenge in modern healthcare,
      particularly given the increasing complexity of therapeutics, an ageing
      population and rising multimorbidity. This article summarises some of the key
      facts about ADRs and explores aspects relating to their prevention, diagnosis,
      reporting and management in current clinical practice.

PMID- 27697817
TI  - Lesson of the month 1: Autoinflammatory syndromes - an unusual cause of pyrexia
      of unknown origin.
AB  - Autoinflammatory diseases are disorders of innate immunity and are characterised
      by recurring and unprovoked episodes of inflammation. We present a case of
      episodic pyrexia, associated with a significant inflammatory response, in a young
      man in whom the cause had remained unexplained since infancy. He was eventually
      diagnosed with hyperimmunoglobulinaemia D syndrome (HIDS); one of the
      autoinflammatory syndromes.

PMID- 27697818
TI  - Lesson of the month 2: An easily missed cause of confusion.
AB  - We describe the case of an 85-year-old woman who developed acute confusion, acute
      kidney injury and temperature spikes while on extended courses of beta-lactams
      for osteomyelitis. The cause of her deterioration was felt to be due to sepsis
      when in fact it was as a result of toxicity from antibiotics. This was
      demonstrated by a rapid resolution in her condition following haemodialysis. We
      also performed a literature review to appraise the neuro and nephrotoxicity of
      various antibiotics and how best to manage toxicity when it occurs.

PMID- 27697819
TI  - Image of the month: Intracranial calcifications due to chronic lead exposure.

PMID- 27697820
TI  - Reviewing post-discharge mortality improves morbidity and mortality processes for
      patients with a general medical hospital admission.

PMID- 27697821
TI  - Neuromuscular conditions for physicians - what you need to know.

PMID- 27697823
TI  - Ultraviolet-Visible (UV-Vis) Microspectroscopic System Designed for the In Situ
      Characterization of the Dehydrogenation Reaction Over Platinum Supported
      Catalytic Microchannel Reactor.
AB  - An ultraviolet visible (UV-Vis) microspectroscopic system was designed for the in
      situ characterization of the activity of the silica supported platinum (Pt)
      catalyst toward the dehydrogenation of 1-methyl-1,4-cyclohexadiene carried out in
      a custom-designed catalytic microreactor cell. The in situ catalytic microreactor
      cell (ICMC) with inlet/outlet ports was prepared using quartz cover as the
      optical window to facilitate UV-Vis observation. A fabricated thermometric stage
      was adapted to the UV-Vis microspectrophotometer to control the reaction
      temperature inside the ICMC. The spectra were collected by focusing the UV-Vis
      beam on a 30 * 30 um area at the center of ICMC. At 393 K, the sequential
      measurement of the spectra recorded during the reaction exhibited a broad
      absorption peak with maximum absorbance at 260 nm that is characteristic for
      gaseous toluene. This result indicates that the silica supported Pt catalyst is
      active towards the dehydrogenation of 1-methyl-1,4-cyclohexadiene at the given
      experimental conditions. The onset of coke formation was also detected based on
      the appearance of absorption bands at 300 nm. The UV-Vis microspectroscopic
      system developed can be used further in studying the mechanism of the
      dehydrogenation reaction.

PMID- 27697824
TI  - The effectiveness of exercise therapy for temporomandibular dysfunction: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate the effectiveness of exercise therapy on pain,
      function, and mobility outcomes in patients with temporomandibular joint
      dysfunction. STUDY DESIGN: Systematic review with meta-analysis. METHODS: A
      systematic review and meta-analysis undertaken following Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses guidelines. Studies that met the
      inclusion criteria: (1) randomized controlled trials; (2) a population with the
      diagnosis of temporomandibular joint dysfunction; and (3) interventions that
      included exercise therapy were considered for review. When studies demonstrated
      homogeneity on outcome measures, the mean differences or standardized mean
      differences with 95% confidence interval were calculated and pooled in a meta
      analysis for pooled synthesis. RESULTS: Six articles with a total of 419
      participants were included in the review and only four studies were included in
      the meta-analysis. Mobility and mixed exercise therapy approaches appear to be
      the most common exercise approaches utilized for management of temporomandibular
      joint dysfunction. Exercise therapy and the associated dosage provide moderate
      short-term and varying long-term benefits in reduction of pain and improvement of
      range of motion of the in patients with temporomandibular joint dysfunction.
      CONCLUSION: Included studies suggest a mobility or a mixed approach to exercise
      therapies have impact on reducing pain, significant impact for increasing range
      of motion, but lack a significant impact for functional improvement. LEVEL OF
      EVIDENCE: Therapy, level 1a-.

PMID- 27697822
TI  - Notch-Mediated Epigenetic Regulation of Voltage-Gated Potassium Currents.
AB  - RATIONALE: Ventricular arrhythmias often arise from the Purkinje-myocyte junction
      and are a leading cause of sudden cardiac death. Notch activation reprograms
      cardiac myocytes to an induced Purkinje-like state characterized by prolonged
      action potential duration and expression of Purkinje-enriched genes. OBJECTIVE:
      To understand the mechanism by which canonical Notch signaling causes action
      potential prolongation. METHODS AND RESULTS: We find that endogenous Purkinje
      cells have reduced peak K+ current, Ito, and IK,slow when compared with
      ventricular myocytes. Consistent with partial reprogramming toward a Purkinje
      like phenotype, Notch activation decreases peak outward K+ current density, as
      well as the outward K+ current components Ito,f and IK,slow. Gene expression
      studies in Notch-activated ventricles demonstrate upregulation of Purkinje
      enriched genes Contactin-2 and Scn5a and downregulation of K+ channel subunit
      genes that contribute to Ito,f and IK,slow. In contrast, inactivation of Notch
      signaling results in increased cell size commensurate with increased K+ current
      amplitudes and mimics physiological hypertrophy. Notch-induced changes in K+
      current density are regulated at least in part via transcriptional changes.
      Chromatin immunoprecipitation demonstrates dynamic RBP-J (recombination signal
      binding protein for immunoglobulin kappa J region) binding and loss of active
      histone marks on K+ channel subunit promoters with Notch activation, and similar
      transcriptional and epigenetic changes occur in a heart failure model.
      Interestingly, there is a differential response in Notch target gene expression
      and cellular electrophysiology in left versus right ventricular cardiac myocytes.
      CONCLUSIONS: In summary, these findings demonstrate a novel mechanism for
      regulation of voltage-gated potassium currents in the setting of cardiac
      pathology and may provide a novel target for arrhythmia drug design.

PMID- 27697825
TI  - Current perspectives on the families of glycoside hydrolases of Mycobacterium
      tuberculosis: their importance and prospects for assigning function to unknowns.
AB  - Glycoside hydrolases (GHs) are enzymes that catalyze the hydrolysis of glycosidic
      bonds in glycoconjugates, oligo- and polysaccharides. A classification of these
      enzymes based on conserved sequence and structure motifs supported by the
      Carbohydrate Active Enzyme (CAZy) database has proven useful in the systematic
      groupings of similar enzymes into families. The human pathogen Mycobacterium
      tuberculosis employs 30 GHs to perform a variety of different functions, which
      can be divided into four broad categories: alpha-glucan metabolism, peptidoglycan
      remodeling, beta-glycan hydrolysis and alpha-demannosylation. The review
      presented here shows how the GHs that have been characterized play a role in each
      category. Expanding the genomic analysis of GH presence to other Mycobacterium
      species has highlighted the importance of certain families-most notably GH13 and
      GH23-in the general genomic make-up of mycobacteria. Since many GHs are still
      uncharacterized and considered as "conserved hypothetical" proteins, the grouping
      of them into respective families provides a strong prediction on their putative
      biological functions.

PMID- 27697826
TI  - Measurement of polyp size at colonoscopy: a proof-of-concept simulation study to
      address technology bias.

PMID- 27697827
TI  - Clinical Predictors of Multiple Organ Dysfunction Syndromes in Pediatric patients
      with Scrub Typhus.
AB  - Scrub typhus can produce multiple organ dysfunction syndrome (MODS). Early
      recognition of the patients at risk of MODS would be helpful in providing timely
      management and reducing the mortality. In all, 449 children with scrub typhus
      were enrolled at three hospitals in Yunnan, China from January 2010 to January
      2015. The patients' clinical status of organ system dysfunction was evaluated on
      the day of discharge from hospital by using standard criteria. The patients were
      classified into MODS present (64 cases, 14.3%) or MODS absent (385 cases, 85.7%).
      Multivariate logistic regression analyses revealed that the prognostic factors
      for MODS included skin rash (odds ratio, OR = 3.3, p = 0.037), time interval form
      treatment to defervescence (OR = 1.2, p = 0.035), hemoglobin (OR = 0.54, p =
      0.041), platelet counts (OR = 0.06, p < 0.001), aspartate-aminotransferase (OR =
      4.7, p = 0.011) and total bilirubin (OR = 2.3, p = 0.013). By describing risk
      factors resulting in MODS in pediatric scrub typhus, our study provides
      clinicians with important information to improve the clinical monitoring and
      prognostication of MODS.

PMID- 27697829
TI  - Timing of Circumcision and Breastfeeding Initiation Among Newborn Boys.
AB  - BACKGROUND AND OBJECTIVES: Newborn circumcision, particularly in the first 24
      hours of life, has been thought to adversely affect breastfeeding initiation.
      However, no studies specifically support an association between early
      circumcision and difficulty with breastfeeding initiation or maintenance. This
      study was designed to determine whether timing of newborn circumcision affects
      rates of exclusive breastfeeding during the first 2 weeks of life. METHODS: A
      retrospective study of 797 newborn boys and their mothers was conducted at a
      large military hospital. Exclusion criteria included gestational age <38 weeks,
      multiple delivery, NICU admission, and absence of maternal intention to
      breastfeed. Multivariable logistic regression models examined the relationship
      between time of elective circumcision and exclusive breastfeeding at 3 time
      points: hospital discharge and the newborn and 2-week outpatient visits. RESULTS:
      Mean infant age at circumcision was 29.7 hours. Thirty-one percent were
      circumcised at <24 hours of age. Rates of exclusive breastfeeding were 66.8%,
      64.1%, and 63.7% at hospital discharge and the newborn and 2-week outpatient
      visits, respectively. In the multivariable model, time of circumcision was not
      significantly associated with exclusive breastfeeding at hospital discharge (odds
      ratio [OR], 1.01; 95% confidence interval [CI], 0.99-1.00; P = .54), the newborn
      outpatient visit (OR, 1.00; 95% CI, 0.99-1.02; P = .84), or the 2-week outpatient
      visit (OR, 0.99; 95% CI 0.98-1.01; P = .44). CONCLUSIONS: There was no
      significant association between timing of elective newborn circumcision and
      exclusive breastfeeding in the first 2 weeks of life. In this setting, early
      circumcision of otherwise healthy, term boys had no deleterious effects on
      breastfeeding initiation or maintenance.

PMID- 27697830
TI  - Erratum.
AB  - Philip J Larkin, Fliss Murtagh, Heather Richardson, Myra Bluebond Langner and
      Sheila Payne (2016) Collaboration: Securing a future for palliative care
      research. Palliative Medicine, September 2016 30:8 709-710, doi:
      10.1177/0269216316661970.

PMID- 27697828
TI  - The relationship between pay day and violent death in Guatemala: a time series
      analysis.
AB  - OBJECTIVE: To assess if violent deaths were associated with pay days in
      Guatemala. DESIGN: Interrupted time series analysis. SETTING: Guatemalan national
      autopsy databases. PARTICIPANTS: Daily violence-related autopsy data for 22 418
      decedents from 2009 to 2012. Data were provided by the Guatemalan National
      Institute of Forensic Sciences. Multiple pay-day lags and other important days
      such as holidays were tested. OUTCOME MEASURES: Absolute and relative estimates
      of excess violent deaths on pay days and holidays. RESULTS: The occurrence of
      violent deaths was not associated with pay days. However, a significant
      association was observed for national holidays, and this association was more
      pronounced when national holidays and pay days occurred simultaneously. This
      effect was observed mainly in males, who constituted the vast majority of violent
      deaths in Guatemala. An estimated 112 (coefficient=3.12; 95% CI 2.15 to 4.08;
      p<0.01) more male violent deaths occurred on holidays than were expected. An
      estimated 121 (coefficient=4.64; 95% CI 3.41 to 5.88; p<0.01) more male violent
      deaths than expected occurred on holidays that coincided with the first 2 days
      following a pay day. CONCLUSIONS: Men in Guatemala experience violent deaths at
      an elevated rate when pay days coincide with national holidays. Efforts to be
      better prepared for violence during national holidays and to prevent violent
      deaths by rescheduling pay days when these days co-occur with national holidays
      should be considered.

PMID- 27697831
TI  - NHS to pilot ways to stop sending mental health patients long distances for
      treatment.

PMID- 27697832
TI  - Rad51 and Rad54 promote noncrossover recombination between centromere repeats on
      the same chromatid to prevent isochromosome formation.
AB  - Centromeres consist of DNA repeats in many eukaryotes. Non-allelic homologous
      recombination (HR) between them can result in gross chromosomal rearrangements
      (GCRs). In fission yeast, Rad51 suppresses isochromosome formation that occurs
      between inverted repeats in the centromere. However, how the HR enzyme prevents
      homology-mediated GCRs remains unclear. Here, we provide evidence that Rad51 with
      the aid of the Swi/Snf-type motor protein Rad54 promotes non-crossover
      recombination between centromere repeats to prevent isochromosome formation.
      Mutations in Rad51 and Rad54 epistatically increased the rates of isochromosome
      formation and chromosome loss. In sharp contrast, these mutations decreased gene
      conversion between inverted repeats in the centromere. Remarkably, analysis of
      recombinant DNAs revealed that rad51 and rad54 increase the proportion of
      crossovers. In the absence of Rad51, deletion of the structure-specific
      endonuclease Mus81 decreased both crossovers and isochromosomes, while the
      cdc27/pol32-D1 mutation, which impairs break-induced replication, did not. We
      propose that Rad51 and Rad54 promote non-crossover recombination between
      centromere repeats on the same chromatid, thereby suppressing crossover between
      non-allelic repeats on sister chromatids that leads to chromosomal
      rearrangements. Furthermore, we found that Rad51 and Rad54 are required for gene
      silencing in centromeres, suggesting that HR also plays a role in the structure
      and function of centromeres.

PMID- 27697833
TI  - UNG protects B cells from AID-induced telomere loss.
AB  - Activation-induced deaminase (AID) initiates antibody gene diversification by
      creating G:U mismatches in the immunoglobulin loci. However, AID also deaminates
      nonimmunoglobulin genes, and failure to faithfully repair these off-target
      lesions can cause B cell lymphoma. In this study, we identify a mechanism by
      which processing of G:U produced by AID at the telomeres can eliminate B cells at
      risk of genomic instability. We show that telomeres are off-target substrates of
      AID and that B cell proliferation depends on protective repair by uracil-DNA
      glycosylase (UNG). In contrast, in the absence of UNG activity, deleterious
      processing by mismatch repair leads to telomere loss and defective cell
      proliferation. Indeed, we show that UNG deficiency reduces B cell clonal
      expansion in the germinal center in mice and blocks the proliferation of tumor B
      cells expressing AID. We propose that AID-induced damage at telomeres acts as a
      fail-safe mechanism to limit the tumor promoting activity of AID when it
      overwhelms uracil excision repair.

PMID- 27697834
TI  - Tumor macrophages are pivotal constructors of tumor collagenous matrix.
AB  - Tumor-associated macrophages (TAMs) promote tumor development, invasion, and
      dissemination by various mechanisms. In this study, using an orthotopic
      colorectal cancer (CRC) model, we found that monocyte-derived TAMs advance tumor
      development by the remodeling of its extracellular matrix (ECM) composition and
      structure. Unbiased transcriptomic and proteomic analyses of (a) TAM-abundant and
      -deficient tumor tissues and (b) sorted tumor-associated and -resident colonic
      macrophage subpopulations defined a distinct TAM-induced ECM molecular signature
      composed of an ensemble of matricellular proteins and remodeling enzymes they
      provide to the tumor microenvironment. Remarkably, many of these ECM proteins are
      specifically increased in human CRC versus healthy colon. Specifically, we
      demonstrate that although differentiating into TAMs, monocytes up-regulate matrix
      remodeling programs associated with the synthesis and assembly of collagenous
      ECM, specifically collagen types I, VI, and XIV. This finding was further
      established by advanced imaging showing that TAMs instruct the deposition, cross
      linking, and linearization of collagen fibers during tumor development,
      especially at areas of tumor invasiveness. Finally, we show that cancer
      associated fibroblasts are significantly outnumbered by TAMs in this model and
      that their expression of collagen XIV and I is reduced by TAM deficiency. Here,
      we outline a novel TAM protumoral function associated with building of the
      collagenous ECM niche.

PMID- 27697835
TI  - Complement pathway amplifies caspase-11-dependent cell death and endotoxin
      induced sepsis severity.
AB  - Cell death and release of proinflammatory mediators contribute to mortality
      during sepsis. Specifically, caspase-11-dependent cell death contributes to
      pathology and decreases in survival time in sepsis models. Priming of the host
      cell, through TLR4 and interferon receptors, induces caspase-11 expression, and
      cytosolic LPS directly stimulates caspase-11 activation, promoting the release of
      proinflammatory cytokines through pyroptosis and caspase-1 activation. Using a
      CRISPR-Cas9-mediated genome-wide screen, we identified novel mediators of caspase
      11-dependent cell death. We found a complement-related peptidase,
      carboxypeptidase B1 (Cpb1), to be required for caspase-11 gene expression and
      subsequent caspase-11-dependent cell death. Cpb1 modifies a cleavage product of
      C3, which binds to and activates C3aR, and then modulates innate immune
      signaling. We find the Cpb1-C3-C3aR pathway induces caspase-11 expression through
      amplification of MAPK activity downstream of TLR4 and Ifnar activation, and
      mediates severity of LPS-induced sepsis (endotoxemia) and disease outcome in
      mice. We show C3aR is required for up-regulation of caspase-11 orthologues,
      caspase-4 and -5, in primary human macrophages during inflammation and that c3aR1
      and caspase-5 transcripts are highly expressed in patients with severe sepsis;
      thus, suggesting that these pathways are important in human sepsis. Our results
      highlight a novel role for complement and the Cpb1-C3-C3aR pathway in
      proinflammatory signaling, caspase-11 cell death, and sepsis severity.

PMID- 27697838
TI  - Estimation after blinded sample size reassessment.
AB  - Blinded sample size reassessment is a popular means to control the power in
      clinical trials if no reliable information on nuisance parameters is available in
      the planning phase. We investigate how sample size reassessment based on blinded
      interim data affects the properties of point estimates and confidence intervals
      for parallel group superiority trials comparing the means of a normal endpoint.
      We evaluate the properties of two standard reassessment rules that are based on
      the sample size formula of the z-test, derive the worst case reassessment rule
      that maximizes the absolute mean bias and obtain an upper bound for the mean bias
      of the treatment effect estimate.

PMID- 27697837
TI  - NFATC3 promotes IRF7 transcriptional activity in plasmacy--toid dendritic cells.
AB  - Plasmacytoid dendritic cells (pDCs) rapidly produce large amounts of type 1
      interferon (IFN) after Toll-like receptor 7 and 9 engagements. This specialized
      function of type 1 IFN production is directly linked to the constitutive
      expression of IRF7, the master transcription factor for type 1 IFN production.
      However, the IRF7 regulatory network in pDCs remains largely unknown. In this
      study, we identify that the transcription factor NFATC3 specifically binds to
      IRF7 and enhances IRF7-mediated IFN production. Furthermore, knockout of NFATC3
      greatly reduced the CpG DNA-induced nuclear translocation of IRF7, which resulted
      in impaired type 1 IFN production in vitro and in vivo. In addition, we found
      that NFATC3 and IRF7 both bound to type 1 IFN promoters and that the NFAT binding
      site in IFN promoters was required for IRF7-mediated IFN expression.
      Collectively, our study shows that the transcription factor NFATC3 binds to IRF7
      and functions synergistically to enhance IRF7-mediated IFN expression in pDCs.

PMID- 27697839
TI  - Heparan Sulfate Regulates the Structure and Function of Osteoprotegerin in
      Osteoclastogenesis.
AB  - Osteoprotegerin (OPG), a decoy receptor secreted by osteoblasts, is a major
      negative regulator of bone resorption. It functions by neutralizing the receptor
      activator of nuclear factor kappaB ligand (RANKL), which plays a central role in
      promoting osteoclastogenesis. OPG is known to be a high-affinity heparan sulfate
      (HS)-binding protein. Presumably, HS could regulate the function of OPG and
      affect how it inhibits RANKL. However, the molecular detail of HS-OPG interaction
      remains poorly understood, which hinders our understanding of how HS functions in
      osteoclastogenesis. Here we report mapping of the HS-binding site of OPG. The HS
      binding site, identified by mutagenesis study, consists of eight basic residues
      that are located mostly at the junction of the second death domain and the C
      terminal domain. We further show that heparin-derived dodecasaccharide is able to
      induce dimerization of OPG monomers with a stoichiometry of 1:1. Small-angle X
      ray scattering analysis revealed that upon binding of HS, OPG undergoes a
      dramatic conformational change, resulting in a more compact and less flexible
      structure. Importantly, we present here three lines of evidence that HS, OPG, and
      RANKL form a stable ternary complex. Using a HS binding-deficient OPG mutant, we
      further show that in an osteoblast/bone marrow macrophage co-culture system,
      immobilization of OPG by HS at the osteoblast cell surface substantially lowers
      the inhibitory threshold of OPG toward RANKL. These discoveries strongly suggest
      that HS plays an active role in regulating OPG-RANKL interaction and
      osteoclastogenesis.

PMID- 27697836
TI  - Preventing tumor escape by targeting a post-proteasomal trimming independent
      epitope.
AB  - Adoptive T cell therapy (ATT) can achieve regression of large tumors in mice and
      humans; however, tumors frequently recur. High target peptide-major
      histocompatibility complex-I (pMHC) affinity and T cell receptor (TCR)-pMHC
      affinity are thought to be critical to preventing relapse. Here, we show that
      targeting two epitopes of the same antigen in the same cancer cells via
      monospecific T cells, which have similar pMHC and pMHC-TCR affinity, results in
      eradication of large, established tumors when targeting the apparently
      subdominant but not the dominant epitope. Only the escape but not the rejection
      epitope required postproteasomal trimming, which was regulated by IFN-gamma,
      allowing IFN-gamma-unresponsive cancer variants to evade. The data describe a
      novel immune escape mechanism and better define suitable target epitopes for ATT.

PMID- 27697840
TI  - MukB-mediated Catenation of DNA Is ATP and MukEF Independent.
AB  - Properly condensed chromosomes are necessary for accurate segregation of the
      sisters after DNA replication. The Escherichia coli condesin is MukB, a
      structural maintenance of chromosomes (SMC)-like protein, which forms a complex
      with MukE and the kleisin MukF. MukB is known to be able to mediate knotting of a
      DNA ring, an intramolecular reaction. In our investigations of how MukB condenses
      DNA we discovered that it can also mediate catenation of two DNA rings, an
      intermolecular reaction. This activity of MukB requires DNA binding by the head
      domains of the protein but does not require either ATP or its partner proteins
      MukE or MukF. The ability of MukB to mediate DNA catenation underscores its
      potential for bringing distal regions of a chromosome together.

PMID- 27697841
TI  - Proprotein Convertase Processing Enhances Peroxidasin Activity to Reinforce
      Collagen IV.
AB  - The basement membrane (BM) is a form of extracellular matrix that underlies cell
      layers in nearly all animal tissues. Type IV collagen, a major constituent of
      BMs, is critical for tissue development and architecture. The enzyme peroxidasin
      (Pxdn), an extracellular matrix-associated protein, catalyzes the formation of
      structurally reinforcing sulfilimine cross-links within the collagen IV network,
      an event essential to basement membrane integrity. Although the catalytic
      function of Pxdn is known, the regulation of its activity remains unclear. In
      this work we show through N-terminal sequencing, pharmacologic studies, and
      mutational analysis that proprotein convertases (PCs) proteolytically process
      human Pxdn at Arg-1336, a location relatively close to its C terminus. PC
      processing enhances the enzymatic activity of Pxdn and facilitates the formation
      of sulfilimine cross-links in collagen IV. Thus, PC processing of Pxdn is a key
      regulatory step that contributes to its function and, therefore, supports BM
      integrity and homeostasis.

PMID- 27697842
TI  - Mammalian Nonmuscle Myosin II Binds to Anionic Phospholipids with Concomitant
      Dissociation of the Regulatory Light Chain.
AB  - Mammalian cells express three Class II nonmuscle myosins (NM): NM2A, NM2B, and
      NM2C. The three NM2s have well established essential roles in cell motility,
      adhesion, and cytokinesis and less well defined roles in vesicle transport and
      other processes that would require association of NM2s with cell membranes.
      Previous evidence for the mechanism of NM2-membrane association includes direct
      interaction of NM2s with membrane lipids and indirect interaction by association
      of NM2s with membrane-bound F-actin or peripheral membrane proteins. Direct
      binding of NM2s to phosphatidylserine-liposomes, but not to phosphatidylcholine
      liposomes, has been reported, but the molecular basis of the interaction between
      NM2s and acidic phospholipids has not been previously investigated. We now show
      that filamentous, full-length NM2A, NM2B, and NM2C and monomeric, non-filamentous
      heavy meromyosin bind to liposomes containing one or more acidic phospholipids
      (phosphatidylserine, phosphatidylinositol 4,5-diphosphate, and
      phosphatidylinositol 3,4,5-triphosphate) but do not bind to 100%
      phosphatidylcholine-liposomes. Binding of NM2s to acidic liposomes occurs
      predominantly through interaction of the liposomes with the regulatory light
      chain (RLC) binding site in the myosin heavy chain with concomitant dissociation
      of the RLC. Phosphorylation of myosin-bound RLC by myosin light chain kinase
      substantially inhibits binding to liposomes of both filamentous NM2 and non
      filamentous heavy meromyosin; the addition of excess unbound RLC, but not excess
      unbound essential light chain, competes with liposome binding. Consistent with
      the in vitro data, we show that endogenous and expressed NM2A associates with the
      plasma membrane of HeLa cells and fibrosarcoma cells independently of F-actin.

PMID- 27697844
TI  - Living with others inside the self: decolonising transplantation, selfhood and
      the body politic in Nalo Hopkinson's Brown Girl in the Ring.
AB  - This article examines anxieties concerning organ transplantation in Nalo
      Hopkinson's prize-winning novel Brown Girl in the Ring (1998). The main focus is
      how this novel re-imagines subjectivity and selfhood as an embodied metaphor for
      the reconfiguring of broader sociopolitical relations. In other words, this
      article analyses the relationship between the transplanted body and the body
      politic, arguing that a post-transplant identity, where there is little
      separation between donor and recipient, is the foundation for a politics based on
      responsibility for others. Such a responsibility poses a challenge to the race
      and class segregation that is integral to the post-apocalyptic world of
      Hopkinson's novel. Transplantation is not a utopian vision of an egalitarian
      society coming together in one body; rather, this biotechnological intervention
      offers a potentially different mode of thinking what it means to work across
      race, class and embodied division, while always recalling the violence that might
      facilitate so-called medical progress.

PMID- 27697845
TI  - Presentation of neurogenic shock within the emergency department.
AB  - BACKGROUND: Injury to the spinal cord can result in loss of sympathetic
      innervation causing a drop in BP and HR, this condition is known as neurogenic
      shock. There is debate among the literature on how and when neurogenic shock
      presents and what values of HR and BP should be used to define it. Previous
      studies do not take into account multiple prehospital and emergency department
      recordings. OBJECTIVE: To improve understanding of how neurogenic shock presents
      in humans, allowing better identification and treatment. METHODS: The Trauma
      Audit and Research Network database for an adult major trauma centre was used to
      isolate patients with a spinal cord injury. Qualifying patients had all available
      BPs and HRs collated into a database. Patients with neurogenic shock were
      isolated, allowing data analysis. RESULTS: Out of 3069 trauma patients, 33 met
      the inclusion criteria, of which 15 experienced neurogenic shock. 87% of the
      patients who had neurogenic shock experienced it within 2 hours of injury.
      Neurogenic shock below the T6 level was less common (p=0.009); however, there
      were still four cases in the cohort. More patients with complete spinal cord
      injury had neurogenic shock (p=0.039). CONCLUSIONS: Neurogenic shock is variable
      and unpredictable. It can present in the prehospital environment and without
      warning in a patient with previously normal vital signs. The medical team should
      be aware of it in all patients with spinal cord injury regardless of injury
      level.

PMID- 27697846
TI  - Mementos from Boots multisensory boxes - Qualitative evaluation of an
      intervention for people with dementia: Innovative practice.
AB  - This qualitative study explored a multisensory (including olfactory) intervention
      for people with dementia. Six themed boxes (e.g. Childhood) containing items
      chosen from the Boots archive designed to encourage conversation were used in
      weekly group sessions. Session participants were people with dementia and care
      staff from a local care home, a trained facilitator and archivists from Boots UK.
      Semi-structured interviews explored participants' experiences of the sessions.
      Interviews were analysed using thematic analysis. The three major themes
      Engagement (subthemes: Inclusiveness; Emotional involvement; Factors that
      supported engagement), What's in the box (subthemes: Contents stimulate memories;
      Mystery, variety and age of items; Value of olfactory stimuli), and A
      conversation starter (subtheme: Opportunity for self-expression) reveal the
      success of the intervention and the value of olfactory stimuli. Multisensory
      boxes including olfactory stimulation can be an engaging intervention with scope
      to refine it for people with dementia and their carers in the wider community.

PMID- 27697843
TI  - Peroxisome proliferator activating receptor-gamma and the podocyte.
AB  - Over the past two decades it has become clear that the glomerular podocyte is a
      key cell in preventing albuminuria, kidney failure and cardiovascular morbidity.
      Understanding the key pathways that protect the podocyte in times of glomerular
      stress, which can also be therapeutically manipulated, are highly attractive. In
      the following review we assess the evidence that the peroxisome proliferator
      activating receptor (PPAR) agonists are beneficial for podocyte and kidney
      function with a focus on PPAR-gamma. We explain our current understanding of the
      mechanisms of action of these agonists and the evidence they are beneficial in
      diabetic and non-diabetic kidney disease. We also outline why these drugs have
      not been widely used for kidney disease in the past but they may be in the
      future.

PMID- 27697847
TI  - The vestibular system is critical for the changes in muscle and bone induced by
      hypergravity in mice.
AB  - Gravity changes concurrently affect muscle and bone as well as induce alterations
      in vestibular signals. However, the role of vestibular signals in the changes in
      muscle and bone induced by gravity changes remains unknown. We therefore
      investigated the effects of vestibular lesions (VL) on the changes in muscle and
      bone induced by 3 g hypergravity for 4 weeks in C57BL/6J mice. Quantitative
      computed tomography analysis revealed that hypergravity increased muscle mass
      surrounding the tibia and trabecular bone mineral content, adjusting for body
      weight in mice. Hypergravity did not affect cortical bone and fat masses
      surrounding the tibia. Vestibular lesions blunted the increases in muscle and
      bone masses induced by hypergravity. Histological analysis showed that
      hypergravity elevated the cross-sectional area of myofiber in the soleus muscle.
      The mRNA levels of myogenic genes such as MyoD, Myf6, and myogenin in the soleus
      muscle were elevated in mice exposed to hypergravity. Vestibular lesions
      attenuated myofiber size and the mRNA levels of myogenic differentiation markers
      enhanced by hypergravity in the soleus muscle. Propranolol, a beta-blocker,
      antagonized the changes in muscle induced by hypergravity. In conclusion, this
      study is the first to demonstrate that gravity changes affect muscle and bone
      through vestibular signals and subsequent sympathetic outflow in mice.

PMID- 27697848
TI  - Comparative Accuracy of 17 Point-of-Care Glucose Meters.
AB  - BACKGROUND: The accuracy of point-of-care blood glucose (BG) meters is important
      for the detection of dysglycemia, calculation of insulin doses, and the
      calibration of continuous glucose monitors. The objective of this study was to
      compare the accuracy of commercially available glucose meters in a challenging
      laboratory study using samples with a wide range of reference BG and hemoglobin
      values. METHODS: Fresh, discarded blood samples from a hospital STAT laboratory
      were either used without modification, spiked with a glucose solution, or
      incubated at 37 degrees C to produce 347 samples with an even distribution across
      reference BG levels from 20 to 440 mg/dl and hemoglobin values from 9 to 16 g/dl.
      We measured the BG of each sample with 17 different commercially available
      glucose meters and the reference method (YSI 2300) at the same time. We
      determined the mean absolute relative difference (MARD) for each glucose meter,
      overall and stratified by reference BG and by hemoglobin level. RESULTS: The
      accuracy of different meters widely, exhibiting a range of MARDs from 5.6% to
      20.8%. Accuracy was lower in the hypoglycemic range, but was not consistently
      lower in samples with anemic blood hemoglobin levels. CONCLUSIONS: The accuracy
      of commercially available glucose meters varies widely. Although the sample mix
      in this study was much more challenging than those that would be collected under
      most use conditions, some meters were robust to these challenges and exhibited
      high accuracy in this setting. These data on relative accuracy and robustness to
      challenging samples may be useful in informing the choice of a glucose meter.

PMID- 27697849
TI  - Occipital nerve stimulation improves the quality of life in medically-intractable
      chronic cluster headache: Results of an observational prospective study.
AB  - Background Occipital nerve stimulation (ONS) has been proposed to treat chronic
      medically-intractable cluster headache (iCCH) in small series of cases without
      evaluation of its functional and emotional impacts. Methods We report the
      multidimensional outcome of a large observational study of iCCH patients, treated
      by ONS within a nationwide multidisciplinary network ( https://clinicaltrials.gov
      NCT01842763), with a one-year follow-up. Prospective evaluation was performed
      before surgery, then three and 12 months after. Results One year after ONS, the
      attack frequency per week was decreased >30% in 64% and >50% in 59% of the 44
      patients. Mean (Standard Deviation) weekly attack frequency decreased from 21.5
      (16.3) to 10.7 (13.8) ( p = 0.0002). About 70% of the patients responded to ONS,
      47.8% being excellent responders. Prophylactic treatments could be decreased in
      40% of patients. Functional (HIT-6 and MIDAS scales) and emotional (HAD scale)
      impacts were significantly improved, as well as the health-related quality of
      life (EQ-5D). The mean (SD) EQ-5D visual analogic scale score increased from 35.2
      (23.6) to 51.9 (25.7) ( p = 0.0037). Surgical minor complications were observed
      in 33% of the patients. Conclusion ONS significantly reduced the attack frequency
      per week, as well as the functional and emotional headache impacts in iCCH
      patients, and dramatically improved the health-related quality of life of
      responders.

PMID- 27697850
TI  - Environment impacts innate immune ontogeny.
AB  - Susceptibility to infection and response to vaccination differ between
      populations and as a function of age. The underlying mechanisms for this age- and
      population-dependent variation are not known. Specifically, it is unclear if
      these variations are due to differences in genetically encoded host programs or
      driven by environmental influences or a combination of both. To address the
      relationship between gene and environment regarding immune ontogeny, we
      determined the innate cytokine responses following PRR stimulation of blood
      mononuclear cells at birth, 1, and 2 yr of age in infants from Caucasian vs .
      Asian parents and were raised in the same city. At birth, we found that innate
      cytokine responses were significantly elevated in Asian compared with Caucasian
      infants. However, these differences waned and responses became more similar over
      the course of 1-2 yr of living in a similar environment. Our observations that
      innate response differences present at birth subsequently equalized rather than
      diverged suggest a key role for environmental effects common to both racial
      groups in shaping the innate immune responses early in life. Delineating the
      underlying environmental factors that modulate innate immune responses early in
      life could provide avenues for targeted beneficial immune modulation.

PMID- 27697851
TI  - Do "Brain-Training" Programs Work?
AB  - In 2014, two groups of scientists published open letters on the efficacy of brain
      training interventions, or "brain games," for improving cognition. The first
      letter, a consensus statement from an international group of more than 70
      scientists, claimed that brain games do not provide a scientifically grounded way
      to improve cognitive functioning or to stave off cognitive decline. Several
      months later, an international group of 133 scientists and practitioners
      countered that the literature is replete with demonstrations of the benefits of
      brain training for a wide variety of cognitive and everyday activities. How could
      two teams of scientists examine the same literature and come to conflicting
      "consensus" views about the effectiveness of brain training?In part, the
      disagreement might result from different standards used when evaluating the
      evidence. To date, the field has lacked a comprehensive review of the brain
      training literature, one that examines both the quantity and the quality of the
      evidence according to a well-defined set of best practices. This article provides
      such a review, focusing exclusively on the use of cognitive tasks or games as a
      means to enhance performance on other tasks. We specify and justify a set of best
      practices for such brain-training interventions and then use those standards to
      evaluate all of the published peer-reviewed intervention studies cited on the
      websites of leading brain-training companies listed on Cognitive Training Data
      (www.cognitivetrainingdata.org), the site hosting the open letter from brain
      training proponents. These citations presumably represent the evidence that best
      supports the claims of effectiveness.Based on this examination, we find extensive
      evidence that brain-training interventions improve performance on the trained
      tasks, less evidence that such interventions improve performance on closely
      related tasks, and little evidence that training enhances performance on
      distantly related tasks or that training improves everyday cognitive performance.
      We also find that many of the published intervention studies had major
      shortcomings in design or analysis that preclude definitive conclusions about the
      efficacy of training, and that none of the cited studies conformed to all of the
      best practices we identify as essential to drawing clear conclusions about the
      benefits of brain training for everyday activities. We conclude with detailed
      recommendations for scientists, funding agencies, and policymakers that, if
      adopted, would lead to better evidence regarding the efficacy of brain-training
      interventions.

PMID- 27697852
TI  - Brain-Training Pessimism, but Applied-Memory Optimism.

PMID- 27697853
TI  - Corrigendum.
AB  - Original article: Bailey, J. M., Vasey, P. L., Diamond, L. M., Breedlove, S. M.,
      Vilain, E., & Epprecht, M. (2016). Sexual orientation, controversy, and science.
      Psychological Science in the Public Interest, 17, 45-101.
      (doi:10.1177/1529100616637616)The original version of this article omitted the
      word "not" in the following sentence: "However, to acknowledge this does imply
      that the social environment shapes sexual orientation" (p. 76). This has been
      corrected in the most recent online version to read "However, to acknowledge this
      does not imply that the social environment shapes sexual orientation."

PMID- 27697855
TI  - Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements
      Predicted to Impact Biological Function and Disease.
AB  - Post-translational modifications (PTMs) regulate protein behavior through
      modulation of protein-protein interactions, enzymatic activity, and protein
      stability essential in the translation of genotype to phenotype in eukaryotes.
      Currently, less than 4% of all eukaryotic PTMs are reported to have biological
      function - a statistic that continues to decrease with an increasing rate of PTM
      detection. Previously, we developed SAPH-ire (Structural Analysis of PTM
      Hotspots) - a method for the prioritization of PTM function potential that has
      been used effectively to reveal novel PTM regulatory elements in discrete protein
      families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of
      eukaryotic protein families containing experimental PTM and 3D structure data -
      capturing 1,325 protein families with 50,839 unique PTM sites organized into
      31,747 modified alignment positions (MAPs), of which 2010 (~6%) possess known
      biological function. Here, we show that using an artificial neural network model
      (SAPH-ire NN) trained to identify MAP hotspots with biological function results
      in prediction outcomes that far surpass the use of single hotspot features,
      including nearest neighbor PTM clustering methods. We find the greatest
      enhancement in prediction for positions with PTM counts of five or less, which
      represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to
      have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of
      truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots
      could be mapped to human KEGG pathways for normal and/or disease physiology. Many
      high-ranking hotspots were also found to be disease-associated pathogenic sites
      of amino acid substitution despite the lack of observable PTM in the human
      protein family member. Taken together, these experiments demonstrate that the
      functional relevance of a PTM can be predicted very effectively by neural network
      models, revealing a large but testable body of potential regulatory elements that
      impact hundreds of different biological processes important in eukaryotic biology
      and human health.

PMID- 27697857
TI  - 2016 William B. Coley Awards.

PMID- 27697858
TI  - IL2 Variant Circumvents ICOS+ Regulatory T-cell Expansion and Promotes NK Cell
      Activation.
AB  - Clinical responses to high-dose IL2 therapy are limited due to selective
      expansion of CD4+CD25+Foxp3+ T-regulatory cells (Treg), especially ICOS+ Tregs,
      rather than natural killer (NK) cells and effector T cells. These ICOS+ Tregs are
      highly suppressive and constitutively express high levels of IL2Ralpha (CD25) and
      CD39. Here, we characterized the effect of a mutant form of IL2 (F42K), which
      preferentially binds to the lower affinity IL2Rbetagamma with reduced binding to
      CD25, on Tregs, effector NK cells, and T-cell subsets. Unlike wild-type (WT) IL2,
      F42K did not efficiently induce the expansion of highly suppressive ICOS+ Tregs
      in peripheral blood mononuclear cells (PBMC) from healthy controls and melanoma
      patients. Instead, it promoted the expansion of CD16+CD56+ NK cells and
      CD56hiCD16- NK cell subsets in both short- and long-term cultures, with enhanced
      Bcl-2 expression. Stimulation of PBMCs with F42K induced expression of more NK
      cell activation molecules, such as NKp30, NKp44, DNAM-1, NKG2D, 4-1BB/CD137, and
      Tim-3, than WT IL2. F42K induced greater upregulation of TRAIL, and NK-mediated
      cytolytic activity was increased against both autologous and HLA-mismatched
      melanoma cells compared with WT IL2. Gene expression analysis revealed distinct
      gene expression profiles stimulated by F42K, WT IL2, and IL15. F42K therapy in
      vivo also induced a dramatic reduction in the expansion of ICOS+ Tregs, promoted
      NK cell expansion, and inhibited melanoma tumor growth more efficiently than WT
      IL2 and more effectively than anti-CTLA-4. Our findings suggest that F42K could
      be a potential substitute for WT IL2 as a cytokine therapy for cancer. Cancer
      Immunol Res; 4(11); 983-94. (c)2016 AACR.

PMID- 27697859
TI  - Transcriptional Maintenance of Pancreatic Acinar Identity, Differentiation, and
      Homeostasis by PTF1A.
AB  - Maintenance of cell type identity is crucial for health, yet little is known of
      the regulation that sustains the long-term stability of differentiated
      phenotypes. To investigate the roles that key transcriptional regulators play in
      adult differentiated cells, we examined the effects of depletion of the
      developmental master regulator PTF1A on the specialized phenotype of the adult
      pancreatic acinar cell in vivo Transcriptome sequencing and chromatin
      immunoprecipitation sequencing results showed that PTF1A maintains the expression
      of genes for all cellular processes dedicated to the production of the secretory
      digestive enzymes, a highly attuned surveillance of unfolded proteins, and a
      heightened unfolded protein response (UPR). Control by PTF1A is direct on target
      genes and indirect through a ten-member transcription factor network. Depletion
      of PTF1A causes an imbalance that overwhelms the UPR, induces cellular injury,
      and provokes acinar metaplasia. Compromised cellular identity occurs by
      derepression of characteristic stomach genes, some of which are also associated
      with pancreatic ductal cells. The loss of acinar cell homeostasis,
      differentiation, and identity is directly relevant to the pathologies of
      pancreatitis and pancreatic adenocarcinoma.

PMID- 27697860
TI  - Absolute Amounts and Status of the Nrf2-Keap1-Cul3 Complex within Cells.
AB  - The transcription factor Nrf2 (NF-E2-related-factor 2) is essential for the
      oxidative and electrophilic stress responses. Keap1 (Kelch-like-ECH-associated
      protein 1), an adaptor for a cullin-3 (Cul3)-based ubiquitin ligase, regulates
      Nrf2 activity through proteasomal degradation, and acts as a sensor for oxidative
      and electrophilic stresses. The Keap1-Cul3 complex is a critical regulator of the
      cellular Nrf2 level, and yet quantitative information regarding their endogenous
      intracellular concentrations in homeostatic conditions and during stress
      responses is unknown. We analyzed the absolute amounts of the Nrf2, Keap1, and
      Cul3 proteins in five murine cell lines by comparison with serial dilutions of
      purified recombinant protein standards in combination with quantitative
      immunoblot analyses. In the basal state, the amount of Nrf2 was maintained at
      lower levels than those of Keap1 and Cul3 proteins, whereas the electrophilic
      agent diethylmaleate dramatically increased Nrf2 to a level greater than that of
      Keap1 and Cul3, resulting in the accumulation of Nrf2 in the nucleus. In
      contrast, Keap1 and Cul3 did not display any changes in their abundance,
      subcellular localization, or interaction in response to electrophilic stimuli.
      Our results demonstrate that the regulation of the Nrf2 protein level during
      stress responses is mediated by the activity but not the composition of the Nrf2
      Keap1-Cul3 complex.

PMID- 27697861
TI  - SIK2 Restricts Autophagic Flux To Support Triple-Negative Breast Cancer Survival.
AB  - Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with
      multiple, distinct molecular subtypes that exhibit unique transcriptional
      programs and clinical progression trajectories. Despite knowledge of the
      molecular heterogeneity of the disease, most patients are limited to generic,
      indiscriminate treatment options: cytotoxic chemotherapy, surgery, and radiation.
      To identify new intervention targets in TNBC, we used large-scale, loss-of
      function screening to identify molecular vulnerabilities among different
      oncogenomic backgrounds. This strategy returned salt inducible kinase 2 (SIK2) as
      essential for TNBC survival. Genetic or pharmacological inhibition of SIK2 leads
      to increased autophagic flux in both normal-immortalized and tumor-derived cell
      lines. However, this activity causes cell death selectively in breast cancer
      cells and is biased toward the claudin-low subtype. Depletion of ATG5, which is
      essential for autophagic vesicle formation, rescued the loss of viability
      following SIK2 inhibition. Importantly, we find that SIK2 is essential for TNBC
      tumor growth in vivo Taken together, these findings indicate that claudin-low
      tumor cells rely on SIK2 to restrain maladaptive autophagic activation.
      Inhibition of SIK2 therefore presents itself as an intervention opportunity to
      reactivate this tumor suppressor mechanism.

PMID- 27697862
TI  - Human PDCD2L Is an Export Substrate of CRM1 That Associates with 40S Ribosomal
      Subunit Precursors.
AB  - Protein arginine methyltransferase 3 (PRMT3) forms a stable complex with 40S
      ribosomal protein S2 (RPS2) and contributes to ribosome biogenesis. However, the
      molecular mechanism by which PRMT3 influences ribosome biogenesis and/or function
      still remains unclear. Using quantitative proteomics, we identified human
      programmed cell death 2-like (PDCD2L) as a novel PRMT3-associated protein. Our
      data suggest that RPS2 promotes the formation of a conserved extraribosomal
      complex with PRMT3 and PDCD2L. We also show that PDCD2L associates with 40S
      subunit precursors that contain a 3'-extended form of the 18S rRNA (18S-E pre
      rRNA) and several pre-40S maturation factors. PDCD2L shuttles between the nucleus
      and the cytoplasm in a CRM1-dependent manner using a leucine-rich nuclear export
      signal that is sufficient to direct the export of a reporter protein. Although
      PDCD2L is not required for the biogenesis and export of 40S ribosomal subunits,
      we found that PDCD2L-null cells accumulate free 60S ribosomal subunits, which is
      indicative of a deficiency in 40S subunit availability. Our data also indicate
      that PDCD2L and its paralog, PDCD2, function redundantly in 40S ribosomal subunit
      production. Our findings uncover the existence of an extraribosomal complex
      consisting of PDCD2L, RPS2, and PRMT3 and support a role for PDCD2L in the late
      maturation of 40S ribosomal subunits.

PMID- 27697863
TI  - Endoplasmic Reticulum Stress Enhances Mitochondrial Metabolic Activity in
      Mammalian Adrenals and Gonads.
AB  - The acute response to stress consists of a series of physiological programs to
      promote survival by generating glucocorticoids and activating stress response
      genes that increase the synthesis of many chaperone proteins specific to
      individual organelles. In the endoplasmic reticulum (ER), short-term stress
      triggers activation of the unfolded protein response (UPR) module that either
      leads to neutralization of the initial stress or adaptation to it; chronic stress
      favors cell death. UPR induces expression of the transcription factor, C/EBP
      homology protein (CHOP), and its deletion protects against the lethal
      consequences of prolonged UPR. Here, we show that stress-induced CHOP expression
      coincides with increased metabolic activity. During stress, the ER and
      mitochondria come close to each other, resulting in the formation of a complex
      consisting of the mitochondrial translocase, translocase of outer mitochondrial
      membrane 22 (Tom22), steroidogenic acute regulatory protein (StAR), and 3beta
      hydroxysteroid dehydrogenase type 2 (3betaHSD2) via its intermembrane space (IMS)
      exposed charged unstructured loop region. Stress increased the circulation of
      phosphates, which elevated pregnenolone synthesis by 2-fold by increasing the
      stability of 3betaHSD2 and its association with the mitochondrion-associated ER
      membrane (MAM) and mitochondrial proteins. In summary, cytoplasmic CHOP plays a
      central role in coordinating the interaction of MAM proteins with the outer
      mitochondrial membrane translocase, Tom22, to activate metabolic activity in the
      IMS by enhanced phosphate circulation.

PMID- 27697865
TI  - Inositol Pyrophosphate Kinase Asp1 Modulates Chromosome Segregation Fidelity and
      Spindle Function in Schizosaccharomyces pombe.
AB  - Chromosome transmission fidelity during mitosis is of critical importance for the
      fitness of an organism, as mistakes will lead to aneuploidy, which has a
      causative role in numerous severe diseases. Proper segregation of chromosomes
      depends on interdependent processes at the microtubule-kinetochore interface and
      the spindle assembly checkpoint. Here we report the discovery of a new element
      essential for chromosome transmission fidelity that implicates inositol
      pyrophosphates (IPPs) as playing a key role in this process. The protein is Asp1,
      the Schizosaccharomyces pombe member of the highly conserved Vip1 family. Vip1
      enzymes are bifunctional: they consist of an IPP-generating kinase domain and a
      pyrophosphatase domain that uses such IPPs as substrates. We show that Asp1
      kinase function is required for bipolar spindle formation. The absence of Asp1
      generated IPPs resulted in errors in sister chromatid biorientation, a prolonged
      checkpoint-controlled delay of anaphase onset, and chromosome missegregation.
      Remarkably, expression of Asp1 variants that generated higher-than-wild-type
      levels of IPPs led to a faster-than-wild-type entry into anaphase A without an
      increase in chromosome missegregation. In fact, the chromosome transmission
      fidelity of a nonessential chromosome was enhanced with increased cellular IPPs.
      Thus, we identified an element that optimized the wild-type chromosome
      transmission process.

PMID- 27697866
TI  - SHP-1 Acts as a Key Regulator of Alloresponses by Modulating LFA-1-Mediated
      Adhesion in Primary Murine T Cells.
AB  - The clinical potential of transplantation is often reduced by T cell-mediated
      alloresponses that cause graft rejection or graft-versus-host disease. Integrin
      mediated adhesion between alloreactive T cells and antigen-presenting cells is
      essential for allorejection. The identity of the signaling events needed for the
      activation of integrins such as LFA-1 is poorly understood. Here, we identified a
      novel role of the protein tyrosine phosphatase SHP-1 in the regulation of murine
      LFA-1-mediated adhesion in an allograft setting. Upon alloactivation, SHP-1
      activity is reduced, resulting in an increase in LFA-1 adhesion compared to that
      for syngeneically activated T cells. The importance of these differential
      activation properties was further indicated by small interfering RNA (siRNA)
      knockdown of SHP-1 in syngeneically and allogeneically stimulated T cells.
      Mechanistically, SHP-1 modulated the binding of SLP-76 to ADAP by
      dephosphorylation of the YDGI tyrosine motif of ADAP, a known docking site for
      the Src family kinase Fyn. This novel key role of SHP-1 in the regulation of LFA
      1-mediated adhesion may provide a new insight into T cell-mediated alloresponses
      and may pave the way to the development of new immunosuppressive pharmaceutical
      agents.

PMID- 27697864
TI  - AMPK and Endothelial Nitric Oxide Synthase Signaling Regulates K-Ras Plasma
      Membrane Interactions via Cyclic GMP-Dependent Protein Kinase 2.
AB  - K-Ras must localize to the plasma membrane and be arrayed in nanoclusters for
      biological activity. We show here that K-Ras is a substrate for cyclic GMP
      dependent protein kinases (PKGs). In intact cells, activated PKG2 selectively
      colocalizes with K-Ras on the plasma membrane and phosphorylates K-Ras at Ser181
      in the C-terminal polybasic domain. K-Ras phosphorylation by PKG2 is triggered by
      activation of AMP-activated protein kinase (AMPK) and requires endothelial nitric
      oxide synthase and soluble guanylyl cyclase. Phosphorylated K-Ras reorganizes
      into distinct nanoclusters that retune the signal output. Phosphorylation acutely
      enhances K-Ras plasma membrane affinity, but phosphorylated K-Ras is
      progressively lost from the plasma membrane via endocytic recycling.
      Concordantly, chronic pharmacological activation of AMPK -> PKG2 signaling with
      mitochondrial inhibitors, nitric oxide, or sildenafil inhibits proliferation of K
      Ras-positive non-small cell lung cancer cells. The study shows that K-Ras is a
      target of a metabolic stress-signaling pathway that can be leveraged to inhibit
      oncogenic K-Ras function.

PMID- 27697867
TI  - Enhanced Stabilization of MCL1 by the Human T-Cell Leukemia Virus Type 1 bZIP
      Factor Is Modulated by Blocking the Recruitment of Cullin 1 to the SCF Complex.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is
      the etiological agent of adult T-cell leukemia (ATL). The HTLV-1 basic leucine
      zipper factor (HBZ), which is encoded by the minus strand of the provirus, is
      constitutively expressed in all ATL patient cells and likely contributes to the
      development and maintenance of ATL. Furthermore, the overexpression of the
      myeloid cell leukemia 1 (MCL1) protein is frequently observed in hematological
      cancers as well as several other types of cancers. Here, we found that the
      expression of HBZ in cells stabilized MCL1 protein expression and suppressed the
      MCL1-mediated release of cytochrome c from the mitochondria. This effect was
      mediated by inhibition of the ubiquitin-dependent degradation of MCL1. In a
      serial binding assay, HBZ interacted with cullin 1 (CUL1) through a head-to-tail
      interaction. The association between CUL1 and Skp1, which serves as the molecular
      scaffold for the components of SCF ubiquitin ligase complexes, was markedly
      repressed in the presence of HBZ. Mechanistic analysis indicated that HBZ
      abrogated the CUL1 association with Skp1, which in turn promoted the cellular
      expression of MCL1. This novel function of HBZ likely plays a role in the viral
      pathogenesis of HTLV-1 and provides important insights into our understanding of
      the development of ATL.

PMID- 27697868
TI  - Comparing the effectiveness of a crowdsourced video and a social marketing video
      in promoting condom use among Chinese men who have sex with men: a study
      protocol.
AB  - INTRODUCTION: Crowdsourcing has been used to spur innovation and increase
      community engagement in public health programmes. Crowdsourcing is the process of
      giving individual tasks to a large group, often involving open contests and
      enabled through multisectoral partnerships. Here we describe one crowdsourced
      video intervention in which a video promoting condom use is produced through an
      open contest. The aim of this study is to determine whether a crowdsourced
      intervention is as effective as a social marketing intervention in promoting
      condom use among high-risk men who have sex with men (MSM) and transgender male
      to-female (TG) in China. METHOD: We evaluate videos developed by crowdsourcing
      and social marketing. The crowdsourcing contest involved an open call for videos.
      Entries were judged on capacity to promote condom use, to be shareable or 'go
      viral' and to give value to the individual. 1170 participants will be recruited
      for the randomised controlled trial. Participants need to be MSM age 16 and over
      who have had condomless anal sex in the last 3 months. Recruitment will be
      through an online banner ad on a popular MSM web page and other social media
      platforms. After completing an initial survey, participants will be randomly
      assigned to view either the social marketing video or the crowdsourcing video.
      Follow-up surveys will be completed at 3 weeks and 3 months after initial
      intervention to evaluate condomless sex and related secondary outcomes. Secondary
      outcomes include condom social norms, condom negotiation, condom self-efficacy,
      HIV/syphilis testing, frequency of sex acts and incremental cost. ETHICS AND
      DISSEMINATION: Approval was obtained from the ethical review boards of the
      Guangdong Provincial Center for Skin Diseases and STI Control, UNC and UCSF. The
      results of this trial will be made available through publication in peer-reviewed
      journals. TRIAL REGISTRATION NUMBER: NCT02516930.

PMID- 27697869
TI  - Improving the well-being of men by Evaluating and Addressing the Gastrointestinal
      Late Effects (EAGLE) of radical treatment for prostate cancer: study protocol for
      a mixed-method implementation project.
AB  - INTRODUCTION: Radiotherapy treatment for prostate cancer can cause bowel
      problems, which may lead to severe difficulties for cancer survivors including
      limiting travel, work or socialising. These symptoms can appear at any time
      following radiotherapy. This study focuses on the early identification and
      protocol-based management of effects known to cause long-term, or even permanent,
      changes to the well-being of prostate cancer survivors. The rationale of this
      study is to improve the care offered to men and their families following pelvic
      radiotherapy for prostate cancer. METHOD AND ANALYSIS: Implementation research
      methodology will be used to adopt a multicomponent intervention at three UK
      centres. The intervention package comprises a standardised clinical assessment of
      relevant symptoms in oncology outpatient clinics and rapid referral to an
      enhanced gastroenterological service for patients identified with bowel problems.
      Gastroenterology staff will be trained to use an expert-practice algorithm of
      targeted gastroenterology investigations and treatments. The evaluation of the
      intervention and its embedding within local practices will be conducted using a
      mixed-methods design. The effect of the new service will be measured in terms of
      the following outcomes: acceptability to staff and patients; quality of life;
      symptom control and cost-effectiveness. Data collection will take place at
      baseline, 6 months (+/-2 months), and 12 months (+/-2 months) after entry into
      the study. ETHICS AND DISSEMINATION: The study has ethical approval from the
      North West-Liverpool East Research Ethics Committee and the appropriate NHS
      governance clearance. All participants provide written informed consent. The
      study team aim to publish the results of the study in peer-reviewed journals as
      well as at national and international conferences. TRIAL REGISTRATION NUMBER:
      UKCRN16974.

PMID- 27697870
TI  - Prevalence, discomfort and self-relief behaviours of painful diabetic neuropathy
      in Taiwan: a cross-sectional study.
AB  - OBJECTIVES: To explore the prevalence, discomfort, and self-relief behaviours of
      painful diabetic neuropathy (PDN) among rural community residents with type 2
      diabetes. DESIGN: A community-based, cross-sectional study. SETTING: This study
      was part of a longitudinal cohort study of a nurse-led health promotion programme
      for preventing foot ulceration in Chiayi County, Taiwan. PARTICIPANTS: Six
      hundred and twenty-eight community adults with type 2 diabetes participated in
      this study. OUTCOME MEASURES: Parameters assessed included peripheral neuropathy,
      peripheral vasculopathy, glycaemic control and metabolic biomarkers. Statistical
      analyses included descriptive statistics and a multivariate logistic regression
      model. RESULTS: About 30.6% of participants (192/628) had PDN. Factors associated
      with PDN included an abnormal ankle brachial index (ABI; OR=3.4; 95% CI 1.9 to
      6.2; p<0.001), Michigan neuropathy screening index (OR=1.69; 95% CI 1.0 to 2.6;
      p=0.021), triglyceride level (OR=1.61; 95% CI 1.0 to 2.4; p=0.036) and being
      female (OR=1.68; 95% CI 1.1 to 2.4; p=0.022). PDN was characterised by
      uncomfortable feelings of prickling, stinging or burning pain and inexplicable
      dullness around the base or dorsal areas of the feet, but received little
      attention or treatment from primary healthcare providers. CONCLUSIONS: A high
      prevalence of PDN was found in rural community residents with type 2 diabetes and
      the healthcare workers provided little attention to, or treatment of, discomfort.
      It is important to identify high-risk groups with PDN early in order to prevent
      foot ulceration and reduce the incidence of amputation of the extremities. It is
      also urgent to develop appropriate treatment and self-relief behaviours to halt
      or reverse the progression of PDN for this population living in rural areas.

PMID- 27697871
TI  - Prevalence and predictors of latent tuberculosis infection among Italian State
      Policemen engaged in assistance to migrants: a national cross-sectional study.
AB  - OBJECTIVES: Better knowledge about tuberculosis (TB) and latent TB infection
      (LTBI) epidemiology is a crucial step for the development of effective strategies
      towards the control and elimination of this deadliest and persistent health
      threat. No study has investigated LTBI epidemiology in policemen who act as an
      interface with cross-border migrants. METHODS: A survey to measure the LTBI
      prevalence and assess the demographic, professional and clinical features
      potentially associated with tuberculin skin test (TST) positivity was performed
      in Italian State Police (ISP) employees engaged, even occasionally, in relief
      activities, hospitality, photographical identification, escorting and
      accompanying of migrants, regardless of contact with active TB cases. Variables
      potentially associated with TST positivity were evaluated with univariate and
      multivariate analysis. RESULTS: From September to December 2014, 4225 ISP workers
      underwent TST screening and completed the questionnaire for data collection,
      according to study procedures. The TST was positive in 9.9% of individuals: no
      active TB cases were registered among the entire study population. Age, previous
      BCG vaccination and work category resulted independently associated with TST
      positivity. CONCLUSIONS: This is the first study providing updated data about
      LTBI epidemiology among ISP employees engaged in assistance to migrants and
      furnish preliminary evidence of possible associations between TST positivity and
      different conditions that need to be deeply investigated with prospective
      studies.

PMID- 27697872
TI  - Identifying different typologies of experiences and coping strategies in men with
      rheumatoid arthritis: a Q-methodology study.
AB  - OBJECTIVE: To identify typologies of experiences and coping strategies of men
      with rheumatoid arthritis (RA). DESIGN: Q-methodology (a qualitative and
      quantitative approach to grouping people according to their subjective opinion).
      Men with RA sorted 64 statements relating to their experience of living with RA
      according to level of agreement across a normal distribution grid. Data were
      examined using Q-factor analysis. SETTING: Rheumatology outpatient departments in
      the UK. PARTICIPANTS: 30 of 65 invited men with RA participated in this study
      (46%). RESULTS: All participants ranked highly the need to be well informed about
      their medication and the importance of keeping a positive attitude. 2 factors
      describing the experiences and coping strategies of male patients living with RA
      were identified: factor A: 'acknowledge, accept and adapt' (n=14) take a
      proactive approach to managing the impact of RA and find different ways of doing
      things; while factor B: 'trying to match up to a macho ideal' (n=8) are
      determined to continue with their pre-RA lives, and therefore push themselves to
      carry on even if this causes them pain. They are frustrated and angry due to the
      impact of RA but they internalise this rather than directing it at others.
      CONCLUSIONS: While some men adapt to their RA by renegotiating their masculine
      identity, others struggle to relinquish their traditional masculine roles.
      Further research is needed to identify whether the finding that there are 2
      distinct groups of men with RA can be generalised, and if so whether the
      differences can be explained by clinical, social or psychological factors, which
      may inform different therapeutic approaches.

PMID- 27697873
TI  - Assessment for the possibility of a first night effect for wrist actigraphy in
      adolescents.
AB  - OBJECTIVES: Evidence of a 'first night effect' has been documented for
      polysomnography. The possibility of this has not been previously assessed in
      wrist actigraphy, yet may have important implications for the study design of
      future sleep research. We sought to examine potential evidence of a 'first night
      effect' for wrist actigraphy in adolescents across weekdays and weekend nights
      for multiple sleep outcomes. DESIGN: 3-year prospective cohort study (Midlands
      Adolescent Schools Sleep Education Study). SETTING: 8 secondary schools in the
      Midlands region of the UK. PARTICIPANTS: Adolescents (aged 11-13 years at
      baseline) were recruited to the study and were requested to wear a wrist
      actigraph for 7 consecutive days/nights at baseline and then annually for 2 years
      during the second term of the academic year. PRIMARY OUTCOME MEASURES: We
      compared multiple sleep outcomes (total sleep time, wake after sleep onset, sleep
      efficiency, sleep onset latency, number of awakenings, length of awakenings,
      sleep onset time) when the device was worn on a weekday and weekend and compared
      these to other nights to identify possible evidence of a 'first night effect' for
      wrist actigraphy. RESULTS: No significant differences were found between any
      sleep outcomes when the first night of wrist actigraphy was on a weekday compared
      with other weekdays. When the first night was measured on a weekend (Friday),
      average total sleep time was significantly greater (486+/-5 min) compared with
      the second night (Saturday; 469+/-6 min), p=0.01. CONCLUSIONS: We found no
      evidence to support a 'first night effect' for wrist actigraphy in our adolescent
      sample. The first night of actigraphy data should not be disregarded in future
      studies that deploy this technique to measure sleep over prolonged time periods.

PMID- 27697874
TI  - Effect of day-case unilateral cochlear implantation in adults on general and
      disease-specific quality of life, postoperative complications and hearing
      results, tinnitus, vertigo and cost-effectiveness: protocol for a randomised
      controlled trial.
AB  - INTRODUCTION: Cochlear implantation is an increasingly common procedure in the
      treatment of severe to profound sensorineural hearing loss (SNHL) in children and
      adults. It is often performed as a day-case procedure. The major drive towards
      day-case surgery has been from a logistical, economical and societal perspective,
      but we also speculate that the patient's quality of life (QoL) is at least equal
      to inpatient surgery if not increased as a result of rapid discharge and
      rehabilitation. Even though cochlear implantation seems well suited to a day-case
      approach and this even seems to be common practice in some countries, evidence is
      scarce and of low quality to guide us towards the preferred treatment option.
      METHODS AND ANALYSIS: A single-centre, non-blinded, randomised, controlled trial
      was designed to (primarily) investigate the effect on general QoL of day-case
      cochlear implantation compared to inpatient cochlear implantation and
      (secondarily) the effect of both methods on (subjective) hearing improvement,
      disease-specific QoL, tinnitus, vertigo and cost-effectiveness. 30 adult patients
      with severe to profound bilateral postlingual SNHL who are eligible for
      unilateral cochlear implantation will be randomly assigned to either the day-case
      or inpatient treatment group. The outcome measures will be assessed using
      auditory evaluations, questionnaires (preoperatively, at 1-week, 3-week, 3-month
      and 1-year follow-up) and costs diaries (weekly during the first month
      postoperatively, after which once in a month until 1-year follow-up).
      Preoperative and postoperative outcomes will be compared. The difference in costs
      and benefit will be represented using the incremental cost utility/effectiveness
      ratio. The analyses will be carried out on an intention-to-treat basis. ETHICS
      AND DISSEMINATION: This research protocol was approved by the Institutional
      Review Board of the UMC Utrecht (NL45590.041.13; V.5, November 2015). The trial
      results will be disseminated through peer-reviewed medical journals and presented
      at scientific conferences. TRIAL REGISTRATION NUMBER: NTR4464; Pre-results.

PMID- 27697875
TI  - Current practices in patient-reported outcome (PRO) data collection in clinical
      trials: a cross-sectional survey of UK trial staff and management.
AB  - OBJECTIVES: Patient-reported outcome measures (PROMs) collected in clinical
      trials should be administered in a standardised way across sites and routinely
      screened for avoidable missing data in order to maximise data quality/minimise
      risk of bias. Recent qualitative findings, however, have raised concerns about
      the consistency of PROM administration in UK trials. The purpose of this study
      was to determine the generalisability of these findings across the wider
      community of trial personnel. DESIGN: Online cross-sectional survey. SETTING:
      Participants were recruited from 55 UK Clinical Research Collaboration Registered
      Clinical Trials Units and 19 Comprehensive Local Research Networks. PARTICIPANTS:
      Research nurses, data managers/coordinators, trial managers and chief/principal
      investigators involved in clinical trials collecting PROMs. ANALYSIS: We
      undertook descriptive analyses of the quantitative data and directed thematic
      analysis of free-text comments. Factors associated with the management of missing
      PRO data were explored using logistic regression. RESULTS: Survey data from 767
      respondents supported the generalisability of qualitative study findings,
      suggesting inconsistencies in PROM administration with regard to: the level of
      assistance given to trial participants; the timing of PROM completion in relation
      to the clinical consultation; and the management of missing data. Having >=10
      years experience in a research role was significantly associated with the
      appropriate management of missing PROM data (OR 2.26 (95% CI 1.06 to 4.82),
      p=0.035). There was a consensus that more PROM guidance was needed in future
      trials and agreement between professional groups about the necessary components.
      CONCLUSIONS: There are inconsistencies in the way PROMs are administered by trial
      staff. Such inconsistencies may reduce the quality of data and have the potential
      to introduce bias. There is a need for improved guidance in future trials that
      support trial personnel in conducting optimal PROM data collection to inform
      patient care.

PMID- 27697876
TI  - Community-based Rehabilitation Training after stroke: protocol of a pilot
      randomised controlled trial (ReTrain).
AB  - INTRODUCTION: The Rehabilitation Training (ReTrain) intervention aims to improve
      functional mobility, adherence to poststroke exercise guidelines and quality of
      life for people after stroke. A definitive randomised controlled trial (RCT) is
      required to assess the clinical and cost-effectiveness of ReTrain, which is based
      on Action for Rehabilitation from Neurological Injury (ARNI). The purpose of this
      pilot study is to assess the feasibility of such a definitive trial and inform
      its design. METHODS AND ANALYSIS: A 2-group, assessor-blinded, randomised
      controlled external pilot trial with parallel mixed-methods process evaluation
      and economic evaluation. 48 participants discharged from clinical rehabilitation
      despite residual physical disability will be individually randomised 1:1 to
      ReTrain (25 sessions) or control (exercise advice booklet). Outcome assessment at
      baseline, 6 and 9 months include Rivermead Mobility Index; Timed Up and Go Test;
      modified Patient-Specific Functional Scale; 7-day accelerometry; Stroke Self
      efficacy Questionnaire, exercise diary, Fatigue Assessment Scale, exercise
      beliefs and self-efficacy questionnaires, SF-12, EQ-5D-5L, Stroke Quality of
      Life, Carer Burden Index and Service Receipt Inventory. Feasibility,
      acceptability and process outcomes include recruitment and retention rates; with
      measurement burden and trial experiences being explored in qualitative interviews
      (20 participants, 3 intervention providers). Analyses include descriptive
      statistics, with 95% CI where appropriate; qualitative themes; intervention
      fidelity from videos and session checklists; rehearsal of health economic
      analysis. ETHICS AND DISSEMINATION: National Health Service (NHS) National
      Research Ethics Service approval granted in April 2015; recruitment started in
      June. Preliminary studies suggested low risk of serious adverse events; however
      (minor) falls, transitory muscle soreness and high levels of postexercise fatigue
      are expected. Outputs include pilot data to inform whether to proceed to a
      definitive RCT and support a funding application; finalised Trainer and
      Intervention Delivery manuals for multicentre replication of ReTrain;
      presentations at conferences, public involvement events; internationally
      recognised peer-reviewed journal publications, open access sources and media
      releases. TRIAL REGISTRATION NUMBER: NCT02429180; Pre-results.

PMID- 27697877
TI  - Arts-based HIV and STI prevention intervention with Northern and Indigenous youth
      in the Northwest Territories: study protocol for a non-randomised cohort pilot
      study.
AB  - INTRODUCTION: Indigenous youth are disproportionately represented in new HIV
      infection rates in Canada. Current and historical contexts of colonisation and
      racism, disconnection from culture and land, as well as intergenerational trauma
      resulting from the legacy of residential schools are social drivers that elevate
      exposure to HIV among Indigenous peoples. Peer-education and arts-based
      interventions are increasingly used for HIV prevention with youth. Yet limited
      studies have evaluated longitudinal effects of arts-based approaches to HIV
      prevention with youth. The authors present a rationale and study protocol for an
      arts-based HIV prevention intervention with Northern and Indigenous youth in the
      Northwest Territories (NWT), Canada. METHODS AND ANALYSIS: This is a multicentre
      non-randomised cohort pilot study using a pretest/post-test design with a 12
      month follow-up. The target population is Northern and Indigenous youth in 18
      communities in the NWT. The aim is to recruit 150 youth using venue-based
      sampling at secondary schools. Participants will be involved in an arts-based
      intervention, Fostering Open eXpression among Youth (FOXY). Participants will
      complete a pretest, post-test survey directly following the intervention, and a
      12-month follow-up. The primary outcome is new or enhanced HIV knowledge, and
      secondary outcomes to include: new or enhanced sexually transmitted infections
      knowledge, and increased self-esteem, resilience, empowerment, safer sex self
      efficacy and cultural connectedness. Mixed effects regression analyses will be
      conducted to evaluate pretest and post-test differences in outcome measurement
      scores. ETHICS AND DISSEMINATION: This study has received approval from the HIV
      Research Ethics Board at the University of Toronto (REB: 31602). In addition, the
      project is currently registered in the NWT with the Aurora Research Institute
      (Licence: 15741). Trial results will be published according to the Transparent
      Reporting of Evaluations with Nonrandomised Designs statement. TRIAL REGISTRATION
      NUMBER: NCT02743026; Pre-results.

PMID- 27697878
TI  - Study protocol of the YP Face IT feasibility study: comparing an online
      psychosocial intervention versus treatment as usual for adolescents distressed by
      appearance-altering conditions/injuries.
AB  - INTRODUCTION: A significant number of adolescents suffer extensive and enduring
      difficulties such as social anxiety, body image dissatisfaction, low self-esteem
      and bullying as a result of conditions or injuries that affect their appearance
      (eg, craniofacial and skin conditions, treatment side effects and scarring).
      Evidence-based psychosocial interventions to meet their specific needs are
      currently lacking. YP Face IT, developed by the UK's Centre for Appearance
      Research in collaboration with clinical experts and young people, is an
      innovative online psychosocial intervention designed to offer this group
      immediate support, advice and coping strategies. It has been endorsed by young
      people, their parents/carers, GPs, clinical psychologists and health
      professionals working with those affected by appearance-related conditions.
      METHODS AND ANALYSIS: Young people aged 12-17 with an appearance-altering
      condition/injury that self-identify as experiencing appearance-related distress,
      teasing or bullying will be invited to participate via GP practices and UK
      charities. Consenting participants will be randomised to the intervention (YP
      Face IT) or the treatment as usual (TAU) control group. Outcome measures will be
      completed by young people and their parents/carers at baseline, 13, 26 and 52
      weeks. Primary outcome measures will be the Body Esteem Scale and the Social
      Anxiety Scale for Adolescents. Participants will complete other health-related
      outcome measures and resource use questionnaires for health economic analysis. We
      will assess recruitment rates, acceptability of the YP Face IT programme,
      adherence and retention to treatment, questionnaire completion rates, variation
      of TAU in Primary Care and the feasibility of GP practice staff supervising young
      people's use of YP Face IT. ETHICS AND DISSEMINATION: This feasibility trial
      protocol (V.1, 3 March 2014), received a favourable ethical opinion from the NRES
      Committee South West-Frenchay (reference number 14/SW/0058). Findings will be
      disseminated through academic peer-reviewed publications, conferences and to
      participating GP practices and charities supporting those with conditions
      affecting appearance. TRIAL REGISTRATION NUMBER: ISRCTN40650639; Pre-results.

PMID- 27697879
TI  - Association between occupational physical activity and myocardial infarction: a
      prospective cohort study.
AB  - OBJECTIVE: Recommendations regarding physical activity typically include both
      leisure time and occupational physical activity. However, the results from
      previous studies on occupational physical activity and the association with
      myocardial infarction have been inconsistent. The aim of this study was to
      investigate if occupational physical activity is associated with the risk of
      myocardial infarction. DESIGN: Prospective cohort study. PARTICIPANTS: Data from
      the Swedish Work, Lipids and Fibrinogen (WOLF) study was used, comprising 9961
      employees (6849 men, 3112 women, mean age 42.7 years) having no history of
      myocardial infarction. The participants were categorised into 3 groups according
      to their level of occupational physical activity. OUTCOME: Data regarding
      incident myocardial infarction were obtained from the Swedish National Patient
      Register and the Cause of Death Register. Cox proportional hazard regression was
      used for estimation of HRs for different levels of occupational physical activity
      in relation to the risk of myocardial infarction. RESULTS: During a mean follow
      up of 13.1 years, 249 cases of incident myocardial infarction were identified. In
      analyses adjusted for age, sex and socioeconomic status, participants standing
      and walking more than 50% of their working day had an HR of 1.13 (95% CI 0.83 to
      1.54), compared with participants seated more than 50% of their working day. The
      corresponding HR for participants whose work included lifting or carrying was
      0.86 (95% CI 0.59 to 1.24). Further adjustment did not alter the results.
      Stratified analyses resulted in a significantly decreased risk for young people
      whose work included lifting or carrying, HR 0.37 (95% CI 0.17 to 0.84), compared
      with younger persons who sat most of their working day. CONCLUSIONS: No
      significant association between occupational physical activity and the risk of
      myocardial infarction was observed in the total group of employees in this study.
      Based on the results from this study, occupational physical activity in general
      does not seem to be enough for reducing the risk of myocardial infarction.

PMID- 27697880
TI  - Study protocol for Chronic Obstructive Pulmonary Disease-Sitting and
      ExacerbAtions Trial (COPD-SEAT): a randomised controlled feasibility trial of a
      home-based self-monitoring sedentary behaviour intervention.
AB  - INTRODUCTION: An acute exacerbation of chronic obstructive pulmonary disease
      (COPD) marks a critical life event, which can lower patient quality of life and
      ability to perform daily activities. Patients with COPD tend to lead inactive and
      highly sedentary lifestyles, which may contribute to reductions in functional
      capacity. Targeting sedentary behaviour (SB) may be more attainable than exercise
      (at a moderate-to-vigorous intensity) for behaviour change in patients following
      an exacerbation. This study aims to evaluate the feasibility and acceptability of
      a 2-week at-home intervention providing education and self-monitoring to reduce
      prolonged periods of SB in patients with COPD discharged following an acute
      exacerbation. METHODS AND ANALYSIS: Patients will be randomised into 1 of 3
      conditions: usual care (control), education or education+feedback. The education
      group will receive information and suggestions about reducing long periods of
      sitting. The education+feedback group will receive real-time feedback on their
      sitting time, stand-ups and step count at home through an inclinometer linked to
      a smart device app. The inclinometer will also provide vibration prompts to
      encourage movement when the wearer has been sedentary for too long. Data will be
      collected during hospital admission and 2 weeks after discharge. Qualitative
      interviews will be conducted with patients in the intervention groups to explore
      patient experiences. Interviews with healthcare staff will also be conducted. All
      data will be collected January to August 2016. The primary outcomes are
      feasibility and acceptability, which will be assessed by qualitative interviews,
      uptake and drop-out rates, reasons for refusing the intervention, compliance, app
      usage and response to vibration prompts. ETHICS AND DISSEMINATION: The research
      ethics committee East Midlands Leicester-Central has provided ethical approval
      for the conduct of this study. The results of the study will be disseminated
      through appropriate conference proceedings and peer-reviewed journals. TRIAL
      REGISTRATION NUMBER: ISRCTN13790881; Pre-results.

PMID- 27697881
TI  - Systematic review protocol assessing the processes for linking clinical trial
      registries and their published results.
AB  - INTRODUCTION: Clinical trial registries are an important source of information
      for tracking clinical trials from their inception through to their reporting, and
      have been used to measure publication bias and outcome reporting bias. Our aim is
      to survey and quantify the processes that have been used to identify links
      between clinical trial registries and published trial reports in studies that
      rely on these links to evaluate the completeness and accuracy of trial reporting.
      METHODS AND ANALYSIS: We will identify studies that describe a process for
      identifying the links between a trial registry included in the WHO International
      Clinical Trial Registry Platform and published trial results, and use those links
      to evaluate the completeness and accuracy of trial reporting. Information
      extracted from the studies will include the purpose and application domain of the
      study, registries used or searched, processes by which the links were identified,
      the study period and proportions for which links were found. We will summarise
      what is known about the number and availability of links between clinical trial
      registries and published results, and examine how automatic linking, inference
      and inquiry processes have been used to identify links since the introduction of
      trial registries. ETHICS AND DISSEMINATION: The systematic review is focused on
      the analysis of secondary data and does not require ethics approval. The results
      of the systematic review will be used to inform standard processes used to
      identify links to and from clinical trial registries in studies that evaluate the
      completeness and accuracy of clinical trial reports, as well as systematic
      reviews. Our findings will be disseminated by publishing the systematic review in
      a peer-reviewed journal, and by engaging with stakeholders from clinical trial
      registries and bibliographic databases.

PMID- 27697883
TI  - The Baby Moves prospective cohort study protocol: using a smartphone application
      with the General Movements Assessment to predict neurodevelopmental outcomes at
      age 2 years for extremely preterm or extremely low birthweight infants.
AB  - INTRODUCTION: Infants born extremely preterm (EP; <28 weeks' gestation) and/or
      with extremely low birth weight (ELBW; <1000 g birth weight) are at increased
      risk for adverse neurodevelopmental outcomes. However, it is challenging to
      predict those EP/ELBW infants destined to have long-term neurodevelopmental
      impairments in order to target early intervention to those in most need. The
      General Movements Assessment (GMA) in early infancy has high predictive validity
      for neurodevelopmental outcomes in preterm infants. However, access to a GMA may
      be limited by geographical constraints and a lack of GMA-trained health
      professionals. Baby Moves is a smartphone application (app) developed for
      caregivers to video and upload their infant's general movements to be scored
      remotely by a certified GMA assessor. The aim of this study is to determine the
      predictive ability of using the GMA via the Baby Moves app for neurodevelopmental
      impairment in infants born EP/ELBW. METHODS AND ANALYSIS: This prospective cohort
      study will recruit infants born EP/ELBW across the state of Victoria, Australia
      in 2016 and 2017. A control group of normal birth weight (>2500 g birth weight),
      term-born (>=37 weeks' gestation) infants will also be recruited as a local
      reference group. Parents will video their infant's general movements at two time
      points between 3 and 4 months' corrected age using the Baby Moves app. Videos
      will be scored by certified GMA assessors and classified as normal or abnormal.
      Parental satisfaction using the Baby Moves app will be assessed via survey.
      Neurodevelopmental outcome at 2 years' corrected age includes developmental delay
      according to the Bayley Scales of Infant and Toddler Development-III and cerebral
      palsy diagnosis. ETHICS AND DISSEMINATION: This study was approved by the Human
      Research and Ethics Committees at the Royal Children's Hospital, The Royal
      Women's Hospital, Monash Health and Mercy Health in Melbourne, Australia. Study
      findings will be disseminated via peer-reviewed publications and conference
      presentations.

PMID- 27697885
TI  - The History of GalaFLEX P4HB Scaffold.
AB  - The GalaFLEX Scaffold (Galatea Surgical, Inc., Lexington, MA) for plastic and
      reconstructive surgery belongs to a new generation of products for soft tissue
      reinforcement made from poly-4-hydroxybutyrate (P4HB). Other members of this new
      family of products include MonoMax Suture (Aesculap AG, Tuttlingen, Germany) for
      soft tissue approximation, BioFiber Scaffold (Tornier, Inc., Edina, MN) for
      tendon repair, and Phasix Mesh (C.R. Bard, Inc., Murray Hill, NJ) for hernia
      repair. Each of these fully resorbable products provides prolonged strength
      retention, typically 50% to 70% strength retention at 12 weeks, and facilitates
      remodeling in vivo to provide a strong, lasting repair. P4HB belongs to a
      naturally occurring class of biopolymers and fibers made from it are uniquely
      strong, flexible, and biocompatible. GalaFLEX Scaffold is comprised of high
      strength, resorbable P4HB monofilament fibers. It is a knitted macroporous
      scaffold intended to elevate, reinforce, and repair soft tissue. The scaffold
      acts as a lattice for new tissue growth, which is rapidly vascularized and
      becomes fully integrated with adjacent tissue as the fibers resorb. In this
      review, we describe the development of P4HB, its production, properties, safety,
      and biocompatibility of devices made from P4HB. Early clinical results and
      current clinical applications of products made from P4HB are also discussed. The
      results of post-market clinical studies evaluating the GalaFLEX Scaffold in
      rhytidectomy and cosmetic breast surgery demonstrate that the scaffold can
      reinforce lifted soft tissue, resulting in persistent surgical results in the
      face and neck at one year, and provide lower pole stability after breast lift at
      one year.

PMID- 27697884
TI  - Photoperiod Modulates Fast Delayed Rectifier Potassium Currents in the Mammalian
      Circadian Clock.
AB  - One feature of the mammalian circadian clock, situated in the suprachiasmatic
      nucleus (SCN), is its ability to measure day length and thereby contribute to the
      seasonal adaptation of physiology and behavior. The timing signal from the SCN,
      namely the 24 hr pattern of electrical activity, is adjusted according to the
      photoperiod being broader in long days and narrower in short days. Vasoactive
      intestinal peptide and gamma-aminobutyric acid play a crucial role in
      intercellular communication within the SCN and contribute to the seasonal changes
      in phase distribution. However, little is known about the underlying ionic
      mechanisms of synchronization. The present study was aimed to identify cellular
      mechanisms involved in seasonal encoding by the SCN. Mice were adapted to long
      day (light-dark 16:8) and short-day (light-dark 8:16) photoperiods and membrane
      properties as well as K+ currents activity of SCN neurons were measured using
      patch-clamp recordings in acute slices. Remarkably, we found evidence for a
      photoperiodic effect on the fast delayed rectifier K+ current, that is, the
      circadian modulation of this ion channel's activation reversed in long days
      resulting in 50% higher peak values during the night compared with the unaltered
      day values. Consistent with fast delayed rectifier enhancement, duration of
      action potentials during the night was shortened and afterhyperpolarization
      potentials increased in amplitude and duration. The slow delayed rectifier,
      transient K+ currents, and membrane excitability were not affected by
      photoperiod. We conclude that photoperiod can change intrinsic ion channel
      properties of the SCN neurons, which may influence cellular communication and
      contribute to photoperiodic phase adjustment.

PMID- 27697886
TI  - Clinical Use of GalaFLEX in Facial and Breast Cosmetic Plastic Surgery.
AB  - : Resolution of ptosis is a key step to the success of many plastic surgery
      procedures. Ptosis is a manifestation of tissue stretch. Tissue stretch can occur
      as a result of the natural aging process or health of the patient, or tissue may
      stretch under added weight or volume, such as when implants are placed. Surgical
      rejuvenation of ptotic tissues is very effective and results in marked changes in
      the patient profile yet the tissue that resulted in the need for the procedure
      first place has not improved and ptosis can recur. Recent developments in long
      term resorbable porous materials have provided surgeons with the opportunity to
      experiment with tissue reinforcement in plastic surgery procedures. These new
      materials have a low profile, rapid tissue integration, and a long-term strength
      retention profile. Long-term resorbable scaffolds such as poly-4-hydroxybutyrate
      (P4HB) natural scaffold (GalaFLEX scaffold, Galatea Surgical, Inc., Lexington,
      MA) have shown promise for a host of plastic surgery indications. This article
      presents clinical experience with GalaFLEX for soft tissue reinforcement in three
      different clinical applications; including the reinforcement of the superficial
      muscular aponeurotic system (SMAS) in minimally invasive facelift, reinforcement
      of the skin envelope in mastopexy, and reinforcement of the breast capsule
      (pocket) in revisional breast surgery. Soft tissue reinforcement has been shown
      to provide increased mechanical strength as well as improved maintenance of
      postoperative results. LEVEL OF EVIDENCE: 5 Therapeutic.

PMID- 27697882
TI  - Fructose intake and risk of gout and hyperuricemia: a systematic review and meta
      analysis of prospective cohort studies.
AB  - BACKGROUND: The prevalence of hyperuricemia and gout has increased in recent
      decades. The role of dietary fructose in the development of these conditions
      remains unclear. OBJECTIVE: To conduct a systematic review and meta-analysis of
      prospective cohort studies investigating the association fructose consumption
      with incident gout and hyperuricemia. DESIGN: MEDLINE, EMBASE and the Cochrane
      Library were searched (through September 2015). We included prospective cohort
      studies that assessed fructose consumption and incident gout or hyperuricemia. 2
      independent reviewers extracted relevant data and assessed study quality using
      the Newcastle-Ottawa Scale. We pooled natural-log transformed risk ratios (RRs)
      using the generic inverse variance method. Interstudy heterogeneity was assessed
      (Cochran Q statistic) and quantified (I2 statistic). The overall quality of the
      evidence was assessed using the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) approach. RESULTS: 2 studies involving 125 299
      participants and 1533 cases of incident gout assessed the association between
      fructose consumption and incident gout over an average of 17 years of follow-up.
      No eligible studies assessed incident hyperuricemia as an outcome. Fructose
      consumption was associated with an increase in the risk of gout (RR=1.62, 95% CI
      1.28 to 2.03, p<0.0001) with no evidence of interstudy heterogeneity (I2=0%,
      p=0.33) when comparing the highest (>11.8% to >11.9% total energy) and lowest
      (<6.9% to <7.5% total energy) quantiles of consumption. LIMITATIONS: Despite a
      dose-response gradient, the overall quality of evidence as assessed by GRADE was
      low, due to indirectness. There were only two prospective cohort studies
      involving predominantly white health professionals that assessed incident gout,
      and none assessed hyperuricemia. CONCLUSIONS: Fructose consumption was associated
      with an increased risk of developing gout in predominantly white health
      professionals. More prospective studies are necessary to understand better the
      role of fructose and its food sources in the development of gout and
      hyperuricemia. PROTOCOL REGISTRATION NUMBER: NCT01608620.

PMID- 27697887
TI  - Alloplastic Soft Tissue Support: An Overview and Clinical Experience.

PMID- 27697888
TI  - Do Processing Methods Make a Difference in Acellular Dermal Matrix Properties?
AB  - BACKGROUND: The use of acellular dermal matrices (ADMs) has become the standard
      of practice in many reconstructive and aesthetic surgical applications. Different
      methods used to prepare the allograft tissue for surgical use can alter the ADMs
      natural properties. Aseptic processing has been shown to retain the natural
      properties of ADMs more favorably than terminally sterilized ADMs. Terminal
      sterilization has been historically linked to alteration of biological materials.
      In vitro work was conducted to compare ADM processing methods. OBJECTIVES:
      Characterize aseptically processed ADMs and compare cell-matrix interaction
      characteristics to terminally sterilized ADMs. METHODS: Two aseptically processed
      ADMs, FlexHD Pliable and BellaDerm, were characterized via histological
      evaluation, biomechanical integrity, enzymatic degradation, and in vitro cell
      studies. FlexHD Pliable was compared to Alloderm Ready-to-Use (RTU). RESULTS:
      Histological evaluation revealed that FlexHD Pliable had a uniform, open
      structure compared to BellaDerm. Mechanical characterization demonstrated that
      BellaDerm had higher strength and stiffness compared to FlexHD Pliable, which
      maintained higher elasticity. Immunohistochemical analysis verified that key
      matrix proteins remained intact after aseptic processing. Cell studies found that
      fibroblasts attached more readily, and proliferated faster on FlexHD Pliable
      compared to BellaDerm. Additionally, fibroblasts infiltrated into FlexHD Pliable
      from both sides and on the dermal side in BellaDerm and produced an abundance of
      multi-layered matrix proteins (collagen, fibronectin) when compared to AlloDerm
      RTU which was sparse. CONCLUSIONS: Aseptically processed FlexHD Pliable and
      BellaDerm provide a suitable, biocompatible option for tissue repair and
      regeneration in aesthetic and reconstructive surgical applications.

PMID- 27697891
TI  - Mohn et al (J Infect Dis 2016; 214:722-31).

PMID- 27697889
TI  - Posterior Shoulder Instability.
AB  - CONTEXT: Posterior shoulder instability has become more frequently recognized and
      treated as a unique subset of shoulder instability, especially in the military.
      Posterior shoulder pathology may be more difficult to accurately diagnose than
      its anterior counterpart, and commonly, patients present with complaints of pain
      rather than instability. "Posterior instability" may encompass both dislocation
      and subluxation, and the most common presentation is recurrent posterior
      subluxation. Arthroscopic and open treatment techniques have improved as
      understanding of posterior shoulder instability has evolved. EVIDENCE
      ACQUISITION: Electronic databases including PubMed and MEDLINE were queried for
      articles relating to posterior shoulder instability. STUDY DESIGN: Clinical
      review. LEVEL OF EVIDENCE: Level 4. RESULTS: In low-demand patients, nonoperative
      treatment of posterior shoulder instability should be considered a first line of
      treatment and is typically successful. Conservative treatment, however, is
      commonly unsuccessful in active patients, such as military members. Those
      patients with persistent shoulder pain, instability, or functional limitations
      after a trial of conservative treatment may be considered surgical candidates.
      Arthroscopic posterior shoulder stabilization has demonstrated excellent clinical
      outcomes, high patient satisfaction, and low complication rates. Advanced
      techniques may be required in select cases to address bone loss, glenoid
      dysplasia, or revision. CONCLUSION: Posterior instability represents about 10% of
      shoulder instability and has become increasingly recognized and treated in
      military members. Nonoperative treatment is commonly unsuccessful in active
      patients, and surgical stabilization can be considered in patients who do not
      respond. Isolated posterior labral repairs constitute up to 24% of operatively
      treated labral repairs in a military population. Arthroscopic posterior
      stabilization is typically considered as first-line surgical treatment, while
      open techniques may be required in complex or revision settings.

PMID- 27697892
TI  - Biomineralization strongly modulates the formation of Proteus mirabilis and
      Pseudomonas aeruginosa dual-species biofilms.
AB  - Proteus mirabilis and Pseudomonas aeruginosa are common pathogens that often form
      biofilms together in catheter-associated urinary tract infections (CAUTI).
      However, the interactions between these two species in biofilms are largely
      unknown. P. mirabilis induces ureolytic biomineralization that substantially
      modifies key biofilm properties including morphology, persistence, and
      recalcitrance to antimicrobial therapy. These processes are well known to
      complicate CAUTI, but the consequences for colonization and persistence of P.
      mirabilis in polymicrobial biofilms have not been explored. Here we characterized
      the role of biomineralization in regulating the development of P. mirabilis and
      P. aeruginosa dual-species biofilms. Time-series observations revealed that the
      dominance of P. mirabilis was synchronized with mineral formation in the biofilm.
      After 24 hours of development, the dual-species biofilm was dominated by P.
      mirabilis, and the distribution of P. mirabilis biomass was strongly correlated
      with the mineral fraction of the biofilm. Conversely, dual-species growth without
      biomineralization yielded strikingly different patterns in the biofilm, with P.
      aeruginosa dominating the biofilm biomass. These results show that
      biomineralization is responsible for the increased success of P. mirabilis in the
      polymicrobial biofilm. Since biofilm biomineralization commonly occurs in diverse
      clinical, natural and engineered systems, these findings imply that
      biomineralization could broadly influence the microbial ecology of multispecies
      biofilms.

PMID- 27697890
TI  - Sex Differences in Time to Return-to-Play Progression After Sport-Related
      Concussion.
AB  - BACKGROUND: Recently, female sports participation has increased, and there is a
      tendency for women to experience more symptoms and variable presentation after
      sport-related concussion (SRC). The purpose of this study was to determine
      whether sex differences exist in time to begin a return-to-play (RTP) progression
      after an initial SRC. HYPOTHESIS: After initial SRC, female athletes (11-20 years
      old) would take longer to begin an RTP progression compared with age-matched male
      athletes. STUDY DESIGN: Retrospective cohort study. LEVEL OF EVIDENCE: Level 3.
      METHODS: A total of 579 participants (365 males [mean age, 15.0 +/- 1.7 years],
      214 females [mean age, 15.2 +/- 1.5 years]), including middle school, high
      school, and collegiate athletes who participated in various sports and
      experienced an initial SRC were included and underwent retrospective chart
      review. The following information was collected: sex, age at injury, sport,
      history of prior concussion, date of injury, and date of initiation of RTP
      progression. Participants with a history of more than 1 concussion or injury
      sustained from non-sport-related activity were excluded. RESULTS: Despite
      American football having the greatest percentage (49.2%) of sport participation,
      female athletes took significantly longer to start an RTP progression after an
      initial SRC (29.1 +/- 26.3 days) compared with age-matched male athletes (22.7 +/
      18.3 days; P = 0.002). CONCLUSION: On average, female athletes took
      approximately 6 days longer to begin an RTP progression compared with age-matched
      male athletes. This suggests that sex differences exist between athletes, aged 11
      to 20 years, with regard to initiation of an RTP progression after SRC. CLINICAL
      RELEVANCE: Female athletes may take longer to recover after an SRC, and
      therefore, may take longer to return to sport. Sex should be considered as part
      of the clinical decision-making process when determining plan of care for this
      population.

PMID- 27697893
TI  - Erratum.
AB  - McWilliams, N. (2016). Training Analysts at William Alanson White. Journal of the
      American Psychoanalytic Association 64(4):NP12. (Original doi:
      10.1177/0003065116667506 ).

PMID- 27697894
TI  - Finding Control Cases and Maintaining Immersion: Challenges and Opportunities.
AB  - Given that surveys, as well as frequent observations by institute faculty,
      indicate that many candidates have difficulty finding control cases and
      maintaining immersion and that many graduate analysts face similar challenges, it
      would seem that psychoanalytic training does not prepare candidates adequately
      for finding patients and practicing analysis while in training and, for many,
      after they have graduated. Although external challenges are formidable, it is by
      identifying and making use of internal challenges to finding cases that
      candidates can develop an analytic mind: the identity, approach, and skills
      necessary not only to graduate but to have the choice to practice clinical
      psychoanalysis post-graduation. Some of the internal challenges and their
      manifestations in different phases of initiating analysis (referrals, initial
      consultation, recommendation) are discussed and two detailed examples are offered
      to illustrate the productive use of candidates' countertransferences in finding
      cases and maintaining immersion. Finally, recommendations for institutional
      solutions are provided.

PMID- 27697895
TI  - Associations with resident physicians' early adoption of electronic cigarettes
      for smoking cessation.
AB  - BACKGROUND: Use of the electronic cigarette for nicotine delivery has increased
      dramatically in recent years. Information continues to emerge on its role as a
      smoking cessation aid, but little is known about resident physician use of the
      device in clinical practice. METHODS: In 2015, an electronic survey was
      administered to resident physicians in one healthcare system in Columbus, Ohio.
      The survey included questions about personal smoking exposure, knowledge,
      beliefs, attitudes about electronic cigarettes and early adoption of electronic
      cigarettes with patients. Data were dichotomised based on a 'stages of change'
      model that assessed resident physician adoption of electronic cigarettes for
      therapeutic use. Data were analysed through chi2 tests and logistic regression
      using ORs and 95% CIs. RESULTS: Of 338 residents, 142 (42%) responded. Of all
      residents, 25 (17.7%) reported that they have been recommending electronic
      cigarettes to their patients for the past 6 months or longer. In the multivariate
      model, residents >=postgraduate year (PGY)-3 (OR=3.68, 95% CI 1.20 to 11.29),
      peer-reviewed article exposure (OR=6.65, 95% CI 1.56 to 28.38) and the view that
      addictive potential is definitely or somewhat less than traditional cigarettes
      (OR=5.05, 95% CI 1.48 to 17.24) were associated with recommendation of electronic
      cigarettes. CONCLUSIONS: Few residents report recommending electronic cigarettes
      to patients who smoke. These residents consider the electronic cigarette less
      addicting than traditional cigarettes, supporting harm reduction strategies over
      strict abstinence. Most residents require further evidence-based education on
      efficacy and long-term safety of electronic cigarettes before recommending to
      their patients.

PMID- 27697896
TI  - Why do doctors choose to leave core medical training?

PMID- 27697897
TI  - Factors associated with subluxation in mallet fracture.
AB  - : Radiographs and medical record of all adult patients with a mallet fracture in
      three hospitals between 2004 and 2014 were reviewed. International Classification
      of Diseases, Ninth Revision (ICD-9) codes and text search in radiographic reports
      were used to identify all acute patients with potential mallet fractures in our
      institutional database. Manually checking, 392 true mallet fractures were
      identified among them, 78 had subluxation at the time of diagnosis and 19 had
      subluxation at a later time point during treatment. Fragment size, fragment
      displacement, and interval between injury and treatment were associated with
      initial and late subluxation. Subluxation was not observed when the fracture size
      was less than 39% of the total articular surface. For each 1% increase in total
      articular surface involvement in fractures with more than 39% involvement, the
      risk of subluxation increased by 4% and for each 1% of displacement, the risk of
      subluxation increased by 4%. LEVEL OF EVIDENCE: IV.

PMID- 27697898
TI  - Comparison of distal radius fracture intra-articular step reduction with volar
      locking plates and K wires: a retrospective review of quality and maintenance of
      fracture reduction.
AB  - : This study investigated the accuracy and maintenance of reduction of intra
      articular steps achieved with closed reduction and percutaneous K wires and open
      reduction and a volar locking plate for the treatment of intra-articular distal
      radius fractures. We performed a retrospective review of 359 patients with an
      intra-articular fracture of their distal radius. Multivariate linear regression
      was undertaken to investigate the influence of multiple variables such as age,
      gender, initial displacement and treatment method on reduction despite
      differences between groups. A total of 36% of patients treated with K wires and
      29% with volar locking plate had a step greater than or equal to 1 mm present on
      the first post-operative radiograph. A total of 23% treated with K wires and 28%
      with volar locking plate had a residual step of 1 mm or more on the last
      available radiograph. There was no difference identified between the two
      techniques for quality of initial reduction or persisting step on the last
      available radiographs. Step behaviour and further reduction of step post
      operatively was similar for both treatment methods. Initial displacement and
      increased age influenced initial reduction. Initial fracture displacement shown
      radiologically was the only variable identified that influenced the persistence
      of a step on post-operative radiographs. LEVEL OF EVIDENCE: IV.

PMID- 27697899
TI  - Somatostatin analogues in acromegaly and gastroenteropancreatic neuroendocrine
      tumours: past, present and future.
AB  - Acromegaly is a hormonal disorder that arises when the pituitary gland secretes
      excess growth hormone (GH), which in turn stimulates a concomitant increase in
      serum insulin-like growth factor 1 (IGF-1) levels. Gastroenteropancreatic
      neuroendocrine tumours (GEP-NET) constitute a heterogeneous group of tumours that
      can secrete serotonin and a variety of peptide hormones that may cause
      characteristic symptoms known as carcinoid syndrome or other symptoms and
      hormonal hypersecretion syndromes depending on the tumour's site of origin.
      Current medical therapy for the treatment of acromegaly and GEP-NET involves the
      administration of somatostatin analogues that effectively suppress excess hormone
      secretion. After its discovery in 1979, octreotide became the first synthetic
      biologically stable somatostatin analogue with a short-acting formulation of
      octreotide introduced into clinical practice in the late 1980s. Lanreotide,
      another somatostatin analogue, became available in the mid-1990s initially as a
      prolonged-release formulation administered every 10 or 14 days. Long-acting
      release formulations of both octreotide (Sandostatin LAR and Novartis) and
      lanreotide (Somatuline Autogel, Ipsen), based on microparticle and nanoparticle
      drug-delivery technologies, respectively, were later developed, which allowed for
      once-monthly administration and improved convenience. First-generation
      somatostatin analogues remain one of the cornerstones of medical therapy in the
      management of pituitary and GEP-NET hormone hypersecretion, with octreotide
      having the longest established efficacy and safety profile of the somatostatin
      analogue class. More recently, pasireotide (Signifor), a next-generation
      multireceptor-targeted somatostatin analogue, has emerged as an alternative
      therapeutic option for the treatment of acromegaly. This review summarizes the
      development and clinical success of somatostatin analogues.

PMID- 27697900
TI  - mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors.
AB  - Medical therapy of pancreatic neuroendocrine tumors (P-NET) may take advantage of
      Everolimus treatment. However, the extent of therapeutic response cannot be
      predicted. This study was aimed to identify the possible predictive markers of
      response to Everolimus in P-NET. We found that Everolimus reduced the cell
      viability and induced apoptosis in primary cultures of 6 P-NET (P-NET-R), where
      the proliferative and antiapoptotic effects of IGF1 were blocked by Everolimus.
      On the contrary, 14 P-NET primary cultures (P-NET-NR) were resistant to
      Everolimus and IGF1, suggesting an involvement of PI3K/AKT/mTOR pathway in the
      mechanism of resistance. The response to Everolimus in vitro was associated with
      an active AKT/mTOR pathway and seemed to be associated with a greater clinical
      aggressiveness. In addition, a patient sensitive to Everolimus in vitro was
      sensitive to this drug in vivo also and showed a positive p-AKT
      immunohistochemistry (IHC) at tissue level. Similarly, a patient resistant to
      Everolimus treatment after surgery was not sensitive to the drug in vitro and had
      a negative p-AKT IHC staining. Therefore, present data confirm that P-NET primary
      cultures may be considered a model for testing medical treatment efficacy and
      that IHC characterization of p-AKT might help in identifying human P-NET who can
      benefit from Everolimus treatment. These data encourage conducting a prospective
      multicenter study involving different groups of P-NET patients treated with
      Everolimus.

PMID- 27697901
TI  - Cytokinin acts through the auxin influx carrier AUX1 to regulate cell elongation
      in the root.
AB  - Hormonal interactions are crucial for plant development. In Arabidopsis,
      cytokinins inhibit root growth through effects on cell proliferation and cell
      elongation. Here, we define key mechanistic elements in a regulatory network by
      which cytokinin inhibits root cell elongation in concert with the hormones auxin
      and ethylene. The auxin importer AUX1 functions as a positive regulator of
      cytokinin responses in the root; mutation of AUX1 specifically affects the
      ability of cytokinin to inhibit cell elongation but not cell proliferation. AUX1
      is required for cytokinin-dependent changes of auxin activity in the lateral root
      cap associated with the control of cell elongation. Cytokinin regulates root cell
      elongation through ethylene-dependent and -independent mechanisms, both hormonal
      signals converging on AUX1 as a regulatory hub. An autoregulatory circuit is
      identified involving the control of ARR10 and AUX1 expression by cytokinin and
      auxin, this circuit potentially functioning as an oscillator to integrate the
      effects of these two hormones. Taken together, our results uncover several
      regulatory circuits controlling interactions of cytokinin with auxin and
      ethylene, and support a model in which cytokinin regulates shootward auxin
      transport to control cell elongation and root growth.

PMID- 27697902
TI  - Demethylation of ERECTA receptor genes by IBM1 histone demethylase affects
      stomatal development.
AB  - DNA methylation and histone modifications interact to modulate gene expression in
      biological organisms. The histone demethylase IBM1 suppresses DNA methylation and
      gene silencing, primarily by targeting genic regions in the Arabidopsis genome.
      The chromatin regulator EDM2 is also required for prevention of genic DNA
      methylation because it maintains IBM1 expression by promoting IBM1 mRNA distal
      polyadenylation. Loss-of-function ibm1 and edm2 mutant plants display a wide
      range of developmental defects, but little is known about which developmentally
      important genes are regulated by IBM1 and EDM2. Here, we show that both ibm1 and
      edm2 mutants display defects in production of stomatal lineage cells, which is
      linked to DNA hypermethylation of the ERECTA family genes, including ER, ERL1 and
      ERL2 Stomatal phenotypes and DNA methylation levels of ER genes in ibm1 and edm2
      mutants are restored by mutations in the genes encoding the histone
      methyltransferase KYP and DNA methyltransferase CMT3. Our data demonstrate that a
      specific plant developmental context is influenced by IBM1-regulated histone
      modification and DNA methylation on the gene body region of the ERECTA receptors.

PMID- 27697905
TI  - Boronic acid treatment phenocopies monopteros by affecting PIN1 membrane
      stability and polar auxin transport in Arabidopsis thaliana embryos.
AB  - Several observations suggest that the micronutrient boron (B) has a stabilising
      role in the plasma membrane (PM), supporting functions in PM-linked (hormone)
      signalling processes. However, this role is poorly characterised. Here we show
      treatment with boronic acids, specific competitors of B, phenocopies the
      Arabidopsis thaliana rootless pattern mutant monopteros. At least in part, this
      is caused by phenylboronic acid (PBA)-induced internalisation of the membrane
      localised auxin efflux carrier PINFORMED1 (PIN1) in the early embryo. PIN1
      internalisation interrupts the feedback signal transduction cascade involving the
      phytohormone auxin, PIN1 and the transcription factor gene MONOPTEROS This
      entails several effects, including abnormal development of vascular cell
      precursors, suppression of MONOPTEROS downstream targets and loss of the root
      auxin maximum - essential signals for root meristem development. While PIN1 is
      internalised, we observe a differential effect of PBA on other proteins, which
      are either unaffected, internalised or, as in the case of the B transporter BOR1,
      stabilised at the PM. These findings suggest a competition of PBA with B for
      plant membrane proteins and might shed light on the function of B at the PM.

PMID- 27697903
TI  - Reversible optogenetic control of kinase activity during differentiation and
      embryonic development.
AB  - A limited number of signaling pathways are repeatedly used to regulate a wide
      variety of processes during development and differentiation. The lack of tools to
      manipulate signaling pathways dynamically in space and time has been a major
      technical challenge for biologists. Optogenetic techniques, which utilize light
      to control protein functions in a reversible fashion, hold promise for modulating
      intracellular signaling networks with high spatial and temporal resolution.
      Applications of optogenetics in multicellular organisms, however, have not been
      widely reported. Here, we create an optimized bicistronic optogenetic system
      using Arabidopsis thaliana cryptochrome 2 (CRY2) protein and the N-terminal
      domain of cryptochrome-interacting basic-helix-loop-helix (CIBN). In a proof-of
      principle study, we develop an optogenetic Raf kinase that allows reversible
      light-controlled activation of the Raf/MEK/ERK signaling cascade. In PC12 cells,
      this system significantly improves light-induced cell differentiation compared
      with co-transfection. When applied to Xenopus embryos, this system enables blue
      light-dependent reversible Raf activation at any desired developmental stage in
      specific cell lineages. Our system offers a powerful optogenetic tool suitable
      for manipulation of signaling pathways with high spatial and temporal resolution
      in a wide range of experimental settings.

PMID- 27697908
TI  - Sensitivity and Bias in the Resolution of Stream-Bounce Stimuli.
AB  - The audiovisual stream-bounce effect refers to the resolution of ambiguous motion
      sequences as streaming or bouncing depending on the presence or absence of a
      sound. We used a novel experimental design and signal detection theory (SDT) to
      determine its sensory or decisional origins. To account for issues raised by Witt
      et al. on the interpretation of SDT results, we devised a pure signal detection
      (as opposed to signal discrimination) paradigm and measured participants'
      sensitivity and criterion when detecting a weak tone concurrent with objectively
      streaming or bouncing visual displays. We observed no change in sensitivity but a
      significant change in criterion with participants' criterion more liberal with
      bouncing targets than for streaming targets with. In a second experiment, we
      tasked participants with detecting a weak tone in noise while viewing an
      ambiguous motion sequence. They also indicated whether the targets appeared to
      stream or bounce. Participants' reported equivalent, mostly bouncing responses
      for hit and false alarm trials, and equivalent, mostly streaming responses for
      correct rejection and miss trials. Further, differences in participants'
      sensitivity and criterion measures for detecting tones in subjectively streaming
      compared to subjectively bouncing targets were inconsistent with sensory factors.
      These results support a decisional account of the sound-induced switch from
      mostly streaming to mostly bouncing responses in audiovisual stream-bounce
      displays.

PMID- 27697906
TI  - Nuclei migrate through constricted spaces using microtubule motors and actin
      networks in C. elegans hypodermal cells.
AB  - Cellular migrations through constricted spaces are a crucial aspect of many
      developmental and disease processes including hematopoiesis, inflammation and
      metastasis. A limiting factor in these events is nuclear deformation. Here, we
      establish an in vivo model in which nuclei can be visualized while moving through
      constrictions and use it to elucidate mechanisms for nuclear migration. C.
      elegans hypodermal P-cell larval nuclei traverse a narrow space that is about 5%
      their width. This constriction is blocked by fibrous organelles, structures that
      pass through P cells to connect the muscles to cuticle. Fibrous organelles are
      removed just prior to nuclear migration, when nuclei and lamins undergo extreme
      morphological changes to squeeze through the space. Both actin and microtubule
      networks are organized to mediate nuclear migration. The LINC complex, consisting
      of the SUN protein UNC-84 and the KASH protein UNC-83, recruits dynein and
      kinesin-1 to the nuclear surface. Both motors function in P-cell nuclear
      migration, but dynein, functioning through UNC-83, plays a more central role as
      nuclei migrate towards minus ends of polarized microtubule networks. Thus, the
      nucleoskeleton and cytoskeleton are coordinated to move nuclei through
      constricted spaces.

PMID- 27697904
TI  - The stage-dependent roles of Ldb1 and functional redundancy with Ldb2 in
      mammalian retinogenesis.
AB  - The Lim domain-binding proteins are key co-factor proteins that assemble with LIM
      domains of the LMO/LIM-HD family to form functional complexes that regulate cell
      proliferation and differentiation. Using conditional mutagenesis and comparative
      phenotypic analysis, we analyze the function of Ldb1 and Ldb2 in mouse retinal
      development, and demonstrate overlapping and specific functions of both proteins.
      Ldb1 interacts with Lhx2 in the embryonic retina and both Ldb1 and Ldb2 play a
      key role in maintaining the pool of retinal progenitor cells. This is
      accomplished by controlling the expression of the Vsx2 and Rax, and components of
      the Notch and Hedgehog signaling pathways. Furthermore, the Ldb1/Ldb2-mediated
      complex is essential for generation of early-born photoreceptors through the
      regulation of Rax and Crx. Finally, we demonstrate functional redundancy between
      Ldb1 and Ldb2. Ldb1 can fully compensate the loss of Ldb2 during all phases of
      retinal development, whereas Ldb2 alone is sufficient to sustain activity of Lhx2
      in both early- and late-stage RPCs and in Muller glia. By contrast, loss of Ldb1
      disrupts activity of the LIM domain factors in neuronal precursors. An intricate
      regulatory network exists that is mediated by Ldb1 and Ldb2, and promotes RPC
      proliferation and multipotency; it also controls specification of mammalian
      retina cells.

PMID- 27697910
TI  - Do You Hear More Piano or Drum Sounds? An Auditory Version of the Solitaire
      Illusion.
AB  - The solitaire illusion is an illusion of numerosity proposed by Frith and Frith.
      In the original version, an apparent number of elements was determined by the
      spatial arrangement of two kinds of elements (black and white marbles). In our
      study, an auditory version of the solitaire illusion was demonstrated.
      Participants were asked to judge if they perceived more drum or piano sounds.
      When half of the piano tones were perceived as lower in pitch than a drum sound
      and the other half higher, piano tones appeared to be arranged in small units,
      leading to numerosity underestimation. Conversely, when all piano tones were
      perceived to be higher in pitch than the drum sounds, they appeared to be
      arranged in a single large unit, leading to numerosity overestimation. Comparable
      to the visual version of the solitaire illusion, the clustering seems to be
      determined by Gestalt principles. In our auditory version, a clear reversal of
      the illusion (numerosity overestimation or underestimation) was observed when
      piano tones appeared to be arranged in a single large cluster or in several small
      clusters, respectively.

PMID- 27697907
TI  - A network of conserved formins, regulated by the guanine exchange factor EXC-5
      and the GTPase CDC-42, modulates tubulogenesis in vivo.
AB  - The C. elegans excretory cell (EC) is a powerful model for tubulogenesis, a
      conserved process that requires precise cytoskeletal regulation. EXC-6, an
      ortholog of the disease-associated formin INF2, coordinates cell outgrowth and
      lumen formation during EC tubulogenesis by regulating F-actin at the tip of the
      growing canal and the dynamics of basolateral microtubules. EXC-6 functions in
      parallel with EXC-5/FGD, a predicted activator of the Rho GTPase Cdc42. Here, we
      identify the parallel pathway: EXC-5 functions through CDC-42 to regulate two
      other formins: INFT-2, another INF2 ortholog, and CYK-1, the sole ortholog of the
      mammalian diaphanous (mDia) family of formins. We show that INFT-2 promotes F
      actin accumulation in the EC, and that CYK-1 inhibits INFT-2 to regulate F-actin
      levels and EXC-6-promoted outgrowth. As INF2 and mDia physically interact and
      cross-regulate in cultured cells, our work indicates that a conserved EXC-5-CDC
      42 pathway modulates this regulatory interaction and that it is functionally
      important in vivo during tubulogenesis.

PMID- 27697911
TI  - Testing Alcohol Myopia Theory: Examining the Effects of Alcohol Intoxication on
      Simultaneous Central and Peripheral Attention.
AB  - The effect of alcohol intoxication on central and peripheral attention was
      examined as a test of Alcohol Myopia Theory (AMT). Previous research has
      supported AMT in the context of visual attention, but few studies have examined
      the effects of alcohol intoxication on central and peripheral attention. The
      study followed a 2 (alcohol treatment) * 2 (array size) * 2 (task type) mixed
      design. Forty-one participants (placebo or intoxicated) viewed an array of four
      or six colored circles, while simultaneously counting the flashes of a centrally
      presented fixation cross. Participants were instructed to prioritize flash
      counting accuracy. The subsequently presented colored probe matched the cued
      peripheral stimulus on 50% of trials. Flash counting and probe identification
      accuracy were recorded. There was a significant main effect of alcohol treatment
      on accuracy scores, as well as an alcohol treatment by task type interaction.
      Accuracy scores for the central flash counting task did not differ between
      treatment groups, but scores for peripheral probe identification were lower in
      the alcohol group. As predicted by AMT, alcohol impairment was greater for
      peripheral probe detection than for the central and prioritized flash counting
      task. The findings support the notion that alcohol intoxication narrows
      attentional focus to the central aspects of a task.

PMID- 27697909
TI  - Light Video Game Play is Associated with Enhanced Visual Processing of Rapid
      Serial Visual Presentation Targets.
AB  - There is mixed evidence that video game players (VGPs) may demonstrate better
      performance in perceptual and attentional tasks than non-VGPs (NVGPs). The rapid
      serial visual presentation task is one such case, where observers respond to two
      successive targets embedded within a stream of serially presented items. We
      tested light VGPs (LVGPs) and NVGPs on this task. LVGPs were better at correct
      identification of second targets whether they were also attempting to respond to
      the first target. This performance benefit seen for LVGPs suggests enhanced
      visual processing for briefly presented stimuli even with only very moderate game
      play. Observers were less accurate at discriminating the orientation of a second
      target within the stream if it occurred shortly after presentation of the first
      target, that is to say, they were subject to the attentional blink (AB). We find
      no evidence for any reduction in AB in LVGPs compared with NVGPs.

PMID- 27697912
TI  - The Influence of Olfactory Contexts on the Sequential Rating of Odor
      Pleasantness.
AB  - When we sequentially evaluate the characteristics of sensory stimuli, our
      evaluation of a current stimulus is influenced by those preceding it. One such
      effect is called hedonic contrast, whereby stimuli are rated more negatively
      (negative contrast) or positively (positive contrast) if they are preceded by
      more or less pleasant stimuli. The present study investigated the characteristics
      of hedonic contrast for olfaction and compared these characteristics with those
      of a more oft-studied modality, vision. The results from two experiments
      indicated that both positive and negative contrasts occurred in the sequential
      rating of picture pleasantness, whereas only negative contrast occurred for
      olfactory ratings. Notably, overrating of hedonically negative odors following a
      positive olfactory context was observed even when participants had already rated
      these same negative odors beforehand; conversely, this did not occur for positive
      contrast for either sense. These findings indicate that negative odors are more
      strongly influenced than positive ones, and the rating of positive stimuli may be
      adjusted to the preceding rating independent of stimulus context. The findings of
      this study revealed the unique characteristics of hedonic contrast for the
      olfactory senses.

PMID- 27697913
TI  - Low-Level Motion Characteristics Do Not Account for Perceptions of Stream-Bounce
      Stimuli.
AB  - The stream-bounce effect refers to a bistable motion stimulus that is interpreted
      as two targets either "streaming" past or "bouncing" off one another, and the
      manipulations that bias responses. Directional bias, according to Bertenthal et
      al., is an account of the effect proposing that low-level motion integration
      promotes streaming, and its disruption leads to bouncing, and it is sometimes
      cited either directly in a bottom-up fashion or indirectly under top-down control
      despite Sekuler and Sekuler finding evidence inconsistent with it. We tested two
      key aspects of the hypothesis: (a) comparable changes in speed should produce
      comparable disruptions and lead to similar effects; and (b) speed changes alone
      should disrupt integration without the need for additional more complex changes
      of motion. We found that target motion influences stream-bounce perception, but
      not as directional bias predicts. Our results support Sekuler and Sekuler and
      argue against the low-level motion signals driving perceptual outcomes in stream
      bounce displays (directly or indirectly) and point to higher level inferential
      processes involving perceptual history and expectation. Directional bias as a
      mechanism should be abandoned and either another specific bottom-up process must
      be proposed and tested or consideration should be given to top-down factors alone
      driving the effect.

PMID- 27697914
TI  - A Common Mechanism for Perceptual Reversals in Motion-Induced Blindness, the
      Troxler Effect, and Perceptual Filling-In.
AB  - Several striking visual phenomena involve a physically present stimulus that
      alternates between being perceived and being "invisible." For example, motion
      induced blindness, the Troxler effect, and perceptual filling-in all consist of
      subjective alternations where an item repeatedly changes from being seen to
      unseen. In the present study, we explored whether these three specific visual
      phenomena share any commonalities in their alternation rates and patterns to
      better understand the mechanisms of each. Data from 69 individuals revealed
      moderate to strong correlations across the three phenomena for the number of
      perceptual disappearances and the accumulated duration of the disappearances.
      Importantly, these effects were not correlated with eye movement patterns
      (saccades) assessed through eye tracking, differences in motion sensitivity as
      indexed by dot coherence and speed perception thresholds, or simple reaction time
      abilities. Principal component analyses revealed a single component that
      explained 67% of the variance for the number of perceptual reversals and 60% for
      the accumulated duration of the disappearances. The temporal dynamics of illusory
      disappearances was also compared for each phenomenon, and normalized durations of
      disappearances were well fit by a gamma distribution with similar shape
      parameters for each phenomenon, suggesting that they may be driven by a single
      oscillatory mechanism.

PMID- 27697916
TI  - Ruptured intracranial dermoid cyst.

PMID- 27697915
TI  - Aglycon diversity of brain sterylglucosides: structure determination of
      cholesteryl- and sitosterylglucoside.
AB  - To date, sterylglucosides have been reported to be present in various fungi,
      plants, and animals. In bacteria, such as Helicobacter pylori, proton NMR
      spectral analysis of isolated 1-O-cholesteryl-beta-d-glucopyranoside (GlcChol)
      demonstrated the presence of an alpha-glucosidic linkage. By contrast, in
      animals, no detailed structural analysis of GlcChol has been reported, in part
      because animal-derived samples contain a high abundance of glucosylceramides
      (GlcCers)/galactosylceramides, which exhibit highly similar chromatographic
      behavior to GlcChol. A key step in vertebrate GlcChol biosynthesis is the
      transglucosylation reaction catalyzed by glucocerebrosidase (GBA)1 or GBA2,
      utilizing GlcCer as a glucose donor. These steps are expected to produce a beta
      glucosidic linkage. Impaired GBA1 and GBA2 function is associated with
      neurological disorders, such as cerebellar ataxia, spastic paraplegia, and
      Parkinson's disease. Utilizing a novel three-step chromatographic procedure, we
      prepared highly enriched GlcChol from embryonic chicken brain, allowing complete
      structural confirmation of the beta-glucosidic linkage by 1H-NMR analysis.
      Unexpectedly, during purification, two additional sterylglucoside fractions were
      isolated. NMR and GC/MS analyses confirmed that the plant-type
      sitosterylglucoside in vertebrate brain is present throughout embryonic
      development. The aglycon structure of the remaining sterylglucoside (GSX-2)
      remains elusive due to its low abundance. Together, our results uncovered
      unexpected aglycon heterogeneity of sterylglucosides in vertebrate brain.

PMID- 27697917
TI  - Editorial: Uteroplacental mingling: who's kissing uNK?

PMID- 27697918
TI  - Editorial: Feel the burn: blocking galectin-12 helps leukemic cells differentiate
      while staying lean.

PMID- 27697919
TI  - Editorial: All that you can B: mirn23a regulates B versus myeloid fates.

PMID- 27697920
TI  - Government urges food industry to cut 20% of sugar and reduce portion sizes.

PMID- 27697921
TI  - Organization of the axon initial segment: Actin like a fence.
AB  - What prevents the movement of membrane molecules between axonal and
      somatodendritic domains is unclear. In this issue, Albrecht et. al. (2016. J.
      Cell Biol. http://dx.doi.org/10.1083/jcb.201603108) demonstrate via high-speed
      single-particle tracking and superresolution microscopy that lipid-anchored
      molecules in the axon initial segment are confined to membrane domains separated
      by periodically spaced actin rings.

PMID- 27697922
TI  - Nuclear envelope rupture is induced by actin-based nucleus confinement.
AB  - Repeated rounds of nuclear envelope (NE) rupture and repair have been observed in
      laminopathy and cancer cells and result in intermittent loss of nucleus
      compartmentalization. Currently, the causes of NE rupture are unclear. Here, we
      show that NE rupture in cancer cells relies on the assembly of contractile actin
      bundles that interact with the nucleus via the linker of nucleoskeleton and
      cytoskeleton (LINC) complex. We found that the loss of actin bundles or the LINC
      complex did not rescue nuclear lamina defects, a previously identified
      determinant of nuclear membrane stability, but did decrease the number and size
      of chromatin hernias. Finally, NE rupture inhibition could be rescued in cells
      treated with actin-depolymerizing drugs by mechanically constraining nucleus
      height. These data suggest a model of NE rupture where weak membrane areas,
      caused by defects in lamina organization, rupture because of an increase in
      intranuclear pressure from actin-based nucleus confinement.

PMID- 27697923
TI  - The Ska complex promotes Aurora B activity to ensure chromosome biorientation.
AB  - Chromosome biorientation and accurate segregation rely on the plasticity of
      kinetochore-microtubule (KT-MT) attachments. Aurora B facilitates KT-MT dynamics
      by phosphorylating kinetochore proteins that are critical for KT-MT interactions.
      Among the substrates whose microtubule and kinetochore binding is curtailed by
      Aurora B is the spindle and kinetochore-associated (Ska) complex, a key factor
      for KT-MT stability. Here, we show that Ska is not only a substrate of Aurora B,
      but is also required for Aurora B activity. Ska-deficient cells fail to biorient
      and display chromosome segregation errors underlying suppressed KT-MT turnover.
      These defects coincide with KNL1-Mis12-Ndc80 network hypophosphorylation, reduced
      mitotic centromere-associated kinesin localization, and Aurora B T-loop
      phosphorylation at kinetochores. We further show that Ska requires its
      microtubule-binding capability to promote Aurora B activity in cells and
      stimulates Aurora B catalytic activity in vitro. Finally, we show that protein
      phosphatase 1 counteracts Aurora B activity to enable Ska kinetochore
      accumulation once biorientation is achieved. We propose that Ska promotes Aurora
      B activity to limit its own microtubule and kinetochore association and to ensure
      that KT-MT dynamics and stability fall within an optimal balance for
      biorientation.

PMID- 27697924
TI  - ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for
      proteasomal degradation.
AB  - Proper dynamic regulation of the spindle is essential for successful cell
      division. However, the molecular mechanisms that regulate spindle dynamics in
      mitosis are not fully understood. In this study, we show that Cullin 5
      interacting suppressor of cytokine signaling box protein ASB7 ubiquitinates DDA3,
      a regulator of spindle dynamics, thereby targeting it for proteasomal
      degradation. The presence of microtubules (MTs) prevented the ASB7-DDA3
      interaction, thus stabilizing DDA3. Knockdown of ASB7 decreased MT polymerization
      and increased the proportion of cells with unaligned chromosomes, and this
      phenotype was rescued by deletion of DDA3. Collectively, these data indicate that
      ASB7 plays a crucial role in regulating spindle dynamics and genome integrity by
      controlling the expression of DDA3.

PMID- 27697927
TI  - Nuclear envelope rupture: Actin fibers are putting the squeeze on the nucleus.
AB  - Cells exhibit transient nuclear envelope ruptures during interphase, but the
      responsible biophysical processes remain unclear. In this issue, Hatch and Hetzer
      (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201603053) show that actin
      fibers constrict the nucleus, causing chromatin protrusions and nuclear membrane
      ruptures at sites with nuclear lamina defects.

PMID- 27697925
TI  - Simple rules for passive diffusion through the nuclear pore complex.
AB  - Passive macromolecular diffusion through nuclear pore complexes (NPCs) is thought
      to decrease dramatically beyond a 30-60-kD size threshold. Using thousands of
      independent time-resolved fluorescence microscopy measurements in vivo, we show
      that the NPC lacks such a firm size threshold; instead, it forms a soft barrier
      to passive diffusion that intensifies gradually with increasing molecular mass in
      both the wild-type and mutant strains with various subsets of phenylalanine
      glycine (FG) domains and different levels of baseline passive permeability.
      Brownian dynamics simulations replicate these findings and indicate that the soft
      barrier results from the highly dynamic FG repeat domains and the diffusing
      macromolecules mutually constraining and competing for available volume in the
      interior of the NPC, setting up entropic repulsion forces. We found that FG
      domains with exceptionally high net charge and low hydropathy near the
      cytoplasmic end of the central channel contribute more strongly to obstruction of
      passive diffusion than to facilitated transport, revealing a compartmentalized
      functional arrangement within the NPC.

PMID- 27697928
TI  - Nanoscopic compartmentalization of membrane protein motion at the axon initial
      segment.
AB  - The axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and
      transmembrane molecules. During AIS establishment, a membrane diffusion barrier
      is formed between the axonal and somatodendritic domains. Recently, an axonal
      periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like
      structures has been discovered. However, whether this structure is related to the
      diffusion barrier function is unclear. Here, we performed single-particle
      tracking time-course experiments on hippocampal neurons during AIS development.
      We analyzed the mobility of lipid-anchored molecules by high-speed single
      particle tracking and correlated positions of membrane molecules with the
      nanoscopic organization of the AIS cytoskeleton. We observe a strong reduction in
      mobility early in AIS development. Membrane protein motion in the AIS plasma
      membrane is confined to a repetitive pattern of ~190-nm-spaced segments along the
      AIS axis as early as day in vitro 4, and this pattern alternates with actin
      rings. Mathematical modeling shows that diffusion barriers between the segments
      significantly reduce lateral diffusion along the axon.

PMID- 27697926
TI  - Opposing roles for SNAP23 in secretion in exocrine and endocrine pancreatic
      cells.
AB  - The membrane fusion of secretory granules with plasma membranes is crucial for
      the exocytosis of hormones and enzymes. Secretion disorders can cause various
      diseases such as diabetes or pancreatitis. Synaptosomal-associated protein 23
      (SNAP23), a soluble N-ethyl-maleimide sensitive fusion protein attachment protein
      receptor (SNARE) molecule, is essential for secretory granule fusion in several
      cell lines. However, the in vivo functions of SNAP23 in endocrine and exocrine
      tissues remain unclear. In this study, we show opposing roles for SNAP23 in
      secretion in pancreatic exocrine and endocrine cells. The loss of SNAP23 in the
      exocrine and endocrine pancreas resulted in decreased and increased fusion of
      granules to the plasma membrane after stimulation, respectively. Furthermore, we
      identified a low molecular weight compound, MF286, that binds specifically to
      SNAP23 and promotes insulin secretion in mice. Our results demonstrate opposing
      roles for SNAP23 in the secretion mechanisms of the endocrine and exocrine
      pancreas and reveal that the SNAP23-binding compound MF286 may be a promising
      drug for diabetes treatment.

PMID- 27697929
TI  - A human in vitro model of Duchenne muscular dystrophy muscle formation and
      contractility.
AB  - Tongue weakness, like all weakness in Duchenne muscular dystrophy (DMD), occurs
      as a result of contraction-induced muscle damage and deficient muscular repair.
      Although membrane fragility is known to potentiate injury in DMD, whether muscle
      stem cells are implicated in deficient muscular repair remains unclear. We
      hypothesized that DMD myoblasts are less sensitive to cues in the extracellular
      matrix designed to potentiate structure-function relationships of healthy muscle.
      To test this hypothesis, we drew inspiration from the tongue and engineered
      contractile human muscle tissues on thin films. On this platform, DMD myoblasts
      formed fewer and smaller myotubes and exhibited impaired polarization of the cell
      nucleus and contractile cytoskeleton when compared with healthy cells. These
      structural aberrations were reflected in their functional behavior, as engineered
      tongues from DMD myoblasts failed to achieve the same contractile strength as
      healthy tongue structures. These data suggest that dystrophic muscle may fail to
      organize with respect to extracellular cues necessary to potentiate adaptive
      growth and remodeling.

PMID- 27697931
TI  - Effects of dietary fat source and supplemental lysophosphatidylcholine on
      performance, immune responses, and ileal nutrient digestibility in broilers fed
      corn/soybean meal- or corn/wheat/soybean meal-based diets.
AB  - Two separate experiments were conducted to investigate the effect of different
      fat sources and a supplemental exogenous emulsifier (lysophosphatidylcholine,
      LPC) on growth performance, antibody production titers, and ileal nutrient
      digestibility in broiler chicks fed with different basal diets. A total of 288
      one-day-old Ross 308 chicks were used for each trial (6 dietary treatments based
      on 3 * 2 factorial arrangements of treatments in both trials) with 4 replicates
      of 12 birds each. Dietary treatments consisted of 3 different fat sources (soy
      oil, SO; soy free fatty acids, SFFA; and palm fat powder, PFP) and 2 LPC levels
      (0 and 0.1% of diet), which were evaluated with 2 different basal diets
      (corn/soybean meal-based diets in Exp. 1, or corn/wheat/soybean meal-based diets
      in Exp. 2). In Exp. 1, average daily feed intake (ADFI) was increased (P < 0.01)
      in birds fed PFP diets compared with those fed SO or SFFA diets. Although
      supplemental LPC decreased (P < 0.01) ADFI, the birds fed SFFA diets had the
      greater ADFI at the presence of LPC (fat source * LPC, P < 0.01). Dietary
      supplementation of LPC caused a 4.6% improvement (P < 0.001) in average daily
      weight gain (ADWG) and consequently improved (P < 0.01) feed conversion ratio
      (FCR). Supplemental LPC was more effective in increasing ADWG in SFFA-containing
      diets, resulted in a significant (P < 0.01) dietary fat source * LPC interaction.
      Dietary inclusion of LPC increased (P < 0.01) bursa weight and improved (P <
      0.05) antibody production titers against sheep red blood cells and Newcastle
      disease virus during primary responses. Ileal digestibility of ether extract (EE)
      was improved (P < 0.05) in birds fed diets containing SO as compared with those
      fed PFP diets; dietary LPC supplementation, however, had no marked effect on
      ileal nutrient digestibility. In Exp. 2, ADWG was greater (P < 0.05) in birds fed
      SO-containing diets compared with PFP-supplemented broiler chicks. Furthermore,
      dietary supplementation with LPC improved (P < 0.05) FCR value by 2.1%. Relative
      thymus weight was greater (P < 0.05) in birds fed LPC-supplemented diets than
      those fed unsupplemented diets. Supplemental LPC increased (P < 0.05) Gumboro
      antibody titer, and the lowest antibody response was allotted to the birds fed
      PFP diets. The greatest (P < 0.05) EE digestibility was assigned to the birds fed
      SO and SFFA diets. The present findings showed that birds fed SFFA-containing
      diets had similar performance as SO birds, and supplemental LPC improved overall
      performance especially in SFFA-fed birds.

PMID- 27697930
TI  - Interaction between xylanase and phytase on the digestibility of corn and a
      corn/soy diet for broiler chickens.
AB  - An experiment was carried out to evaluate the digestibility and metabolizability
      of corn and a corn/soy-based diet with the inclusion or not of xylanase and/or
      phytase in broilers. In the trial, 1,120 broiler chicks were distributed
      according to a completely randomized experimental design, consisting of 16
      treatments, with 10 replicates of 7 birds each. Treatments were evaluated
      following a factorial arrangement (4 * 2 * 2), with 4 xylanase levels (zero, 50,
      100, or 150 fungal beta-xylanase units/kg; FXU), 2 phytase levels (zero or 1,000
      phytase units/kg; FTU), and 2 diets (corn/soy or pure corn). The same basal diets
      were fed from one to 14 d post hatch for all birds, after which the experimental
      diets were provided until d 25. All birds were euthanized on d 25 for collection
      of ileal contents. Samples of feed, excreta, and ileal digesta were analyzed for
      determination of apparent ileal digestibility. The effect of xylanase on the
      coefficient of apparent dry matter metabolizability and apparent metabolizable
      energy was increased by the presence of phytase in the complete diet but not in
      the diet based on pure corn resulting in a diet*phytase*xylanase interaction (P <
      0.01; P < 0.001, respectivaly). Equivalent effects were observed for the apparent
      coefficient of ileal protein digestibility in which xylanase effects were
      potentiated by the presence of phytase only in the complete diet, resulting in a
      significant 3-way interaction. In corn there was a limitation in improving
      digestibility when we added increasing levels of xylanase with phytase. Otherwise
      in the corn/soy-based diets, the enzymes were potencialized when they were added
      together. The fact that the effect of xylanase was enhanced by the presence of
      phytase in complete diets but not in pure corn may be associated with differences
      in substrate (arabinoxylan and/or phytate) concentration and presentation, diet
      nutrient balance, or other factors. It can be concluded that the interactive
      effects of xylanase and phytase can be substantial but may depend on the
      characteristics of the diet fed.

PMID- 27697932
TI  - Effects of dietary recombinant chlorella supplementation on growth performance,
      meat quality, blood characteristics, excreta microflora, and nutrient
      digestibility in broilers.
AB  - The use of chlorella as an immune stimulant to enhance nonspecific host defense
      mechanisms or as an antimicrobial to inhibit bacterial growth has been reported.
      Thus, the aim of the present study was to clarify the effect of recombinant
      chlorella supplementation on growth performance, meat quality, and the blood
      profile, excreta microflora, and nutrient digestibility in broilers. A total of
      375 one-day-old ROSS 308 broilers (male and female) were allotted to 5 dietary
      treatments using 5 cages with 15 chicks per cage. Treatments were: 1) NC, basal
      diet supplemented with 1.0% E. coli fermented liquor (EFL); 2) PC1, 0.2% EFL with
      chlorella; 3) PC2, 1.0% EFL with chlorella; 4) T1, 0.2% EFL with chlorella (anti
      viral); and 5) T2, 1.0% EFL with chlorella (anti-viral). The broilers in the T2
      treatment groups showed higher body weight gain (BGW) by 2.55% (P < 0.01) and
      lower feed conversion ratio (FCR) by 2.75% (P < 0.05) compared with those fed the
      control NC treatment group. Moreover, the blood contents of blood urea nitrogen
      (BUN), creatinine, and IgA in the broilers of the T2 treatment group were
      significantly increased by 28.12, 23.07, and 29.72%, respectively -more than
      those found in the broilers of the NC treatment group (P < 0.01). In contrast,
      the LDL/C in the blood from the animals in the T2 treatment group was
      significantly decreased by 23.23% - more than that in the blood from the NC
      broilers (P < 0.05). Based on these results, we suggest that the dietary
      supplementation of broilers with recombinant chlorella could improve their growth
      performance, increase the concentration of IgA and apparently metabolizable
      nitrogen in the blood, and decrease ammonia emissions. Therefore, our findings
      have important implications for the effect of recombinant chlorella
      supplementation through increasing the concentration of IgA and the level of
      metabolizable nitrogen.

PMID- 27697933
TI  - Gene expression of amino acid transporter in pigeon (Columbia livia) intestine
      during post-hatch development and its correlation with amino acid in pigeon milk.
AB  - This study was conducted to evaluate gene expression of the amino acid
      transporter in post-hatch pigeon small intestine and the association of pigeon
      milk amino acid with the above transporter's gene expression. A total of 48
      pigeon breeding families were randomly allocated to 8 groups of 6 replicates of
      one parental pigeon pair and 2 squabs. Samples of pigeon milk and duodenum,
      jejunum, and ileum were collected on d 1, 2, 3, 4, 6, 8, 10, and 14 post hatch.
      The results showed that levels of crude protein (8.93 to 15.56%) were highest in
      pigeon milk on an air-dry basis. Amino acid content in pigeon milk remained
      constant in the first 4 d, declined abruptly at d 6, then increased dramatically
      from d 8 to 14. There was a significant effect of interaction between age and
      intestinal segments on those amino acid transporters gene expression. mRNA
      abundance of ATB0'+, SNAT-2, LAT-4, rBAT, b0'+AT, EAAT-3 and PAT-1 was highest in
      the ileum; B0AT1, asc-1, and IMINO were predominate in the jejunum; and CAT-1 and
      y+LAT2 were greatest in the duodenum. Age-related changes of amino acid
      transporter mRNA was inconsistent. mRNA levels of SNAT-2, rBAT, y+LAT2, b0'+AT,
      and EAAT-3 ascended with age, whereas that of asc-1, CAT-1, and IMINO diminished
      significantly. Levels of B0AT1 and PAT-1 mRNA abundance were minimized at d 6.
      However, few correlations were found between pigeon milk amino acid and the amino
      acid transporter gene expressions in squab small intestine. Our findings provide
      a comprehensive elaboration on ontogeny of the amino acid transporter in post
      hatch pigeon intestine.

PMID- 27697934
TI  - Infographic. Golf and health.

PMID- 27697936
TI  - Better targeting care for individuals with low back pain: opportunities and
      obstacles.

PMID- 27697937
TI  - Exercise-based programmes reduce sports injury in adolescents (PEDro synthesis).

PMID- 27697938
TI  - Evidence from prospective cohort studies does not support current dietary fat
      guidelines: a systematic review and meta-analysis.
AB  - OBJECTIVES: National dietary guidelines were introduced in 1977 and 1983, by the
      US and UK governments to reduce coronary heart disease (CHD) mortality by
      reducing dietary fat intake. Our 2016 systematic review examined the
      epidemiological evidence available to the dietary committees at the time; we
      found no support for the recommendations to restrict dietary fat. The present
      investigation extends our work by re-examining the totality of epidemiological
      evidence currently available relating to dietary fat guidelines. METHODS: A
      systematic review and meta-analysis of prospective cohort studies currently
      available, which examined the relationship between dietary fat, serum cholesterol
      and the development of CHD, were undertaken. RESULTS: Across 7 studies, involving
      89 801 participants (94% male), there were 2024 deaths from CHD during the mean
      follow-up of 11.9+/-5.6 years. The death rate from CHD was 2.25%. Eight data sets
      were suitable for inclusion in meta-analysis; all excluded participants with
      previous heart disease. Risk ratios (RRs) from meta-analysis were not
      statistically significant for CHD deaths and total or saturated fat consumption.
      The RR from meta-analysis for total fat intake and CHD deaths was 1.04 (95% CI
      0.98 to 1.10). The RR from meta-analysis for saturated fat intake and CHD deaths
      was 1.08 (95% CI 0.94 to 1.25). CONCLUSIONS: Epidemiological evidence to date
      found no significant difference in CHD mortality and total fat or saturated fat
      intake and thus does not support the present dietary fat guidelines. The evidence
      per se lacks generalisability for population-wide guidelines.

PMID- 27697940
TI  - NCI's state and community research initiative: a model for future tobacco control
      research.

PMID- 27697941
TI  - National Cancer Institute's leadership role in promoting State and Community
      Tobacco Control research.
AB  - The National Cancer Institute (NCI) has been at the vanguard of funding tobacco
      control research for decades with major efforts such as the Community
      Intervention Trial for Smoking Cessation (COMMIT) in 1988 and the American Stop
      Smoking Intervention Study (ASSIST) in 1991, followed by the Tobacco Research
      Initiative for State and Community Interventions in 1999. Most recently, in 2011,
      the NCI launched the State and Community Tobacco Control (SCTC) Research
      Initiative to address gaps in secondhand smoke policies, tax and pricing
      policies, mass media countermeasures, community and social norms and tobacco
      marketing. The initiative supported large scale research projects and time
      sensitive ancillary pilot studies in response to expressed needs of state and
      community partners. This special issue of Tobacco Control showcases exciting
      findings from the SCTC. In this introductory article, we provide a brief account
      of NCI's historical commitment to promoting research to inform tobacco control
      policy.

PMID- 27697939
TI  - The relationships between golf and health: a scoping review.
AB  - OBJECTIVE: To assess the relationships between golf and health. DESIGN: Scoping
      review. DATA SOURCES: Published and unpublished reports of any age or language,
      identified by searching electronic databases, platforms, reference lists,
      websites and from consulting experts. REVIEW METHODS: A 3-step search strategy
      identified relevant published primary and secondary studies as well as grey
      literature. Identified studies were screened for final inclusion. Data were
      extracted using a standardised tool, to form (1) a descriptive analysis and (2) a
      thematic summary. RESULTS AND DISCUSSION: 4944 records were identified with an
      initial search. 301 studies met criteria for the scoping review. Golf can provide
      moderate intensity physical activity and is associated with physical health
      benefits that include improved cardiovascular, respiratory and metabolic
      profiles, and improved wellness. There is limited evidence related to golf and
      mental health. The incidence of golfing injury is moderate, with back injuries
      the most frequent. Accidental head injuries are rare, but can have serious
      consequences. CONCLUSIONS: Practitioners and policymakers can be encouraged to
      support more people to play golf, due to associated improved physical health and
      mental well-being, and a potential contribution to increased life expectancy.
      Injuries and illnesses associated with golf have been identified, and risk
      reduction strategies are warranted. Further research priorities include
      systematic reviews to further explore the cause and effect nature of the
      relationships described. Research characterising golf's contribution to muscular
      strengthening, balance and falls prevention as well as further assessing the
      associations and effects between golf and mental health are also indicated.

PMID- 27697942
TI  - Success in the city: the road to implementation of Tobacco 21 and Sensible
      Tobacco Enforcement in New York City.
AB  - New York City, a leader in municipal tobacco control in the USA, furthered its
      goal of reducing the community's burden of tobacco use in 2014 by implementing
      Sensible Tobacco Enforcement and Tobacco 21. These policies are intended to
      restrict youth access and eliminate sources of cheap tobacco. Strong
      partnerships, substantial local data and support from the public and elected
      officials were key in overcoming many challenges and ensuring these policies were
      signed into law.

PMID- 27697943
TI  - Minimal intervention delivered by 2-1-1 information and referral specialists
      promotes smoke-free homes among 2-1-1 callers: a Texas generalisation trial.
AB  - BACKGROUND: Replication of intervention research is reported infrequently,
      limiting what we know about external validity and generalisability. The Smoke
      Free Homes Program, a minimal intervention, increased home smoking bans by United
      Way 2-1-1 callers in randomised controlled trials in Atlanta, Georgia and North
      Carolina. OBJECTIVE: Test the programme's generalisability-external validity in a
      different context. METHODS: A randomised controlled trial (n=508) of English
      speaking callers from smoking-discordant households (>=1 smoker and >=1 non
      smoker). 2-1-1 Texas/United Way HELPLINE call specialists serving the Texas Gulf
      Coast recruited callers and delivered three mailings and one coaching call,
      supported by an online tracking system. Data collectors, blind to study
      assignment, conducted telephone interviews 3 and 6 months postbaseline. RESULTS:
      At 3 months, more intervention households reported a smoke-free home (46.6% vs
      25.4%, p<0.0001; growth model intent-to-treat OR=1.48, 95% CI 1.241 to 1.772,
      p<0.0001). At 6 months, self-reported full bans were 62.9% for intervention
      participants and 38.4% for controls (OR=2.19). Texas trial participants were
      predominantly women (83%), single-smoker households (76%) and African-American
      (65%); half had incomes <=US$10 000/year (50%). Texas recruitment was <50% of the
      other sites. Fewer callers reported having a smoker in the household. Almost
      twice the callers with a household smoker declined interest in the
      programme/study. CONCLUSIONS: Our findings in a region with lower smoking rates
      and more diverse callers, including English-speaking Latinos, support programme
      generalisability and convey evidence of external validity. Our recruitment
      experience indicates that site-specific adjustments might improve recruitment
      efficiency and reach. TRIAL REGISTRATION NUMBER: NCT02097914, Results.

PMID- 27697944
TI  - Breathing clean air is Sa'ah Naaghai Bik'eh Hozhoo (SNBH): a culturally centred
      approach to understanding commercial smoke-free policy among the Dine (Navajo
      People).
AB  - INTRODUCTION: Indigenous worldviews and research approaches are fundamental to
      make meaning of complex health issues and increase the likelihood of identifying
      existing cultural protective factors that have contributed to the resilience and
      survival of Indigenous people worldwide. OBJECTIVE: We describe the process for
      applying the Dine (Navajo) paradigm of Sa'ah Naaghai Bik'eh Hozhoo (SNBH), a
      belief system that guides harmonious living, and demonstrate how the application
      of SNBH enhances understanding of Navajo principles for well-being. Specifically,
      we juxtapose this analysis with a conventional qualitative analysis to illuminate
      and interpret Dine perspectives on the health and economic impact of commercial
      secondhand smoke and smoke-free policy. METHODS: Focus groups were conducted
      throughout Navajo Nation to assess the appeal and impact of several evidence
      based messages regarding the health and economic impact of smoke-free policy.
      RESULTS: Dine perspectives have shifted away from family and cultural teachings
      considered protective of a smoke-free life, and struggle to balance the ethical
      and economics of respect for individual and collective rights to live and work in
      smoke-free environments. CONCLUSIONS: Indigenous-centred approaches to public
      health research and policy analysis contribute to understanding the cultural
      knowledge, practices and beliefs that are protective of the health and well-being
      of Indigenous people.

PMID- 27697945
TI  - Advancing smoke-free policy adoption on the Navajo Nation.
AB  - BACKGROUND: Comprehensive smoke-free laws are effective at protecting non-smokers
      and reducing tobacco use, yet they are not widely adopted by tribal governments.
      METHODS: A series of smoke-free policy initiatives on the Navajo Nation,
      beginning in 2008, were reviewed to identify key issues, successes and setbacks.
      RESULTS: It has been essential that proposed policies acknowledge the Navajo
      people's spiritual use of nat'oh, a sacred plant used for gift-giving, medicinal
      purposes and traditional ceremonies, while simultaneously discouraging a secular
      use of commercial tobacco. Concern that smoke-free policies economically harm
      tribal casinos has been a major barrier to broad implementation of comprehensive
      smoke-free laws in Navajo Nation. CONCLUSIONS: It is necessary for tobacco
      control researchers and advocates to build relationships with tribal leaders and
      casino management in order to develop the business case that will take
      comprehensive smoke-free policies to scale throughout tribal lands.

PMID- 27697947
TI  - Tobacco retail policy landscape: a longitudinal survey of US states.
AB  - BACKGROUND: There are ~380 000 tobacco retailers in the USA, where the largest
      tobacco companies spend almost $9 billion a year to promote their products. No
      systematic survey has been conducted of state-level activities to regulate the
      retail environment, thus little is known about what policies are being planned,
      proposed or implemented. METHODS: This longitudinal study is the first US survey
      of state tobacco control programmes (TCPs) about retail policy activities.
      Surveyed in 2012 and 2014, programme managers (n=46) reported activities in
      multiple domains: e-cigarettes, retailer density and licensing, non-tax price
      increases, product placement, advertising and promotion, health warnings and
      other approaches. Policy activities were reported in one of five levels: no
      formal activity, planning or advocating, policy was proposed, policy was enacted
      or policy was implemented. Overall and domain-specific activity scores were
      calculated for each state. RESULTS: The average retail policy activity almost
      doubled between 2012 and 2014. States with the largest increase in scores
      included: Minnesota, which established a fee-based tobacco retail licensing
      system and banned self-service for e-cigarettes and all other tobacco products
      (OTP); Oregon, Kansas and Maine, all of which banned self-service for OTP; and
      West Virginia, which banned some types of flavoured OTP. CONCLUSIONS: Retail
      policy activities in US states increased dramatically in a short time. Given what
      is known about the impact of the retail environment on tobacco use by youth and
      adults, state and local TCPs may want diversify policy priorities by implementing
      retail policies alongside tax and smoke-free air laws.

PMID- 27697946
TI  - Estimating cigarette tax avoidance and evasion: evidence from a national sample
      of littered packs.
AB  - INTRODUCTION: A number of recent studies document the proportion of all cigarette
      packs that are 'contraband' using discarded packs to measure tax avoidance and
      evasion, which we call tax non-compliance. To date, academic studies using
      discarded packs focused on relatively small geographical areas such as a city or
      a neighbourhood. METHODS: We visited 160 communities across 38 US states in 2012
      and collected data from littered cigarette packs as part of the State and
      Community Tobacco Control (SCTC) Research Initiative and the Bridging the Gap
      Community Obesity Measures Project (BTG-COMP). Data collectors were trained in a
      previously tested littered pack data collection protocol. RESULTS: Field teams
      collected 2116 packs with cellophane across 132 communities. We estimate a
      national tax non-compliance rate of 18.5% with considerable variation across
      regions. Suburban areas had lower non-compliance than urban areas as well as
      areas with high and low median household income areas compared with middle income
      areas. DISCUSSION: We present the first academic national study of tax non
      compliance using littered cigarette packs. We demonstrate the feasibility of
      meaningful large-scale data collection using this methodology and document
      considerable variation in tax non-compliance across areas, suggesting that both
      policy differences and geography may be important in control of illicit tobacco
      use. Given the geography of open borders among countries with varying tax rates,
      this simple methodology may be appropriate to estimate tax non-compliance in
      countries that use tax stamps or other pack markings, such as health warnings.

PMID- 27697948
TI  - Do state minimum markup/price laws work? Evidence from retail scanner data and
      TUS-CPS.
AB  - BACKGROUND: Minimum markup/price laws (MPLs) have been proposed as an alternative
      non-tax pricing strategy to reduce tobacco use and access. However, the empirical
      evidence on the effectiveness of MPLs in increasing cigarette prices is very
      limited. This study aims to fill this critical gap by examining the association
      between MPLs and cigarette prices. METHODS: State MPLs were compiled from primary
      legal research databases and were linked to cigarette prices constructed from the
      Nielsen retail scanner data and the self-reported cigarette prices from the
      Tobacco Use Supplement to the Current Population Survey. Multivariate regression
      analyses were conducted to examine the association between MPLs and the major
      components of MPLs and cigarette prices. RESULTS: The presence of MPLs was
      associated with higher cigarette prices. In addition, cigarette prices were
      higher, above and beyond the higher prices resulting from MPLs, in states that
      prohibit below-cost combination sales; do not allow any distributing party to use
      trade discounts to reduce the base cost of cigarettes; prohibit distributing
      parties from meeting the price of a competitor, and prohibit distributing below
      cost coupons to the consumer. Moreover, states that had total markup rates >24%
      were associated with significantly higher cigarette prices. CONCLUSIONS: MPLs are
      an effective way to increase cigarette prices. The impact of MPLs can be further
      strengthened by imposing greater markup rates and by prohibiting coupon
      distribution, competitor price matching, and use of below-cost combination sales
      and trade discounts.

PMID- 27697949
TI  - Comparing projected impacts of cigarette floor price and excise tax policies on
      socioeconomic disparities in smoking.
AB  - BACKGROUND: About half of all US states have cigarette minimum price laws (MPLs)
      that require a per cent mark-up on prices, but research suggests they may not be
      very effective in raising prices. An alternative type of MPL sets a floor price
      below which packs cannot be sold, and may be more promising. This new type of MPL
      policy has only been implemented in 1 city, therefore its benefits relative to
      excise taxes is difficult to assess. METHODS: We constructed a set of possible
      state floor price MPL options, and matched them to possible state excise tax
      hikes designed to produce similar average price increases. Using self-reported
      price and cigarette consumption data from 23 521 participants in the 2010-2011
      Tobacco Use Supplement of the Current Population Survey, we projected changes in
      pack prices and cigarette consumption following implementation of each paired MPL
      and tax option, for lower and higher income groups. RESULTS: We project that
      state MPLs set at the average reported pack price would raise prices by $0.33 and
      reduce cigarette consumption by about 4%; a tax with a similar average price
      effect would reduce consumption by 2.3%. MPLs and taxes that raise average prices
      by more than $2.00 would reduce consumption by 15.9% and 13.5%, respectively. In
      all models, we project that MPLs will reduce income-based smoking disparities
      more than their comparable excise taxes. CONCLUSIONS: Floor price cigarette MPLs
      set at or above what consumers currently report paying could reduce both tobacco
      use and socioeconomic disparities in smoking.

PMID- 27697950
TI  - Standardized Tobacco Assessment for Retail Settings (STARS): dissemination and
      implementation research.
AB  - OBJECTIVE: The Standardized Tobacco Assessment for Retail Settings (STARS) was
      designed to characterise the availability, placement, promotion and price of
      tobacco products, with items chosen for relevance to regulating the retail
      tobacco environment. This study describes the process to develop the STARS
      instrument and protocol employed by a collaboration of US government agencies, US
      state tobacco control programmes (TCPs), advocacy organisations, public health
      attorneys and researchers from the National Cancer Institute's State and
      Community Tobacco Control (SCTC) Research Initiative. METHODS: To evaluate
      dissemination and early implementation experiences, we conducted telephone
      surveys with state TCP leaders (n=50, response rate=100%), and with individuals
      recruited via a STARS download registry on the SCTC website. Website registrants
      were surveyed within 6 months of the STARS release (n=105, response rate=66%) and
      again after ~5 months (retention rate=62%). RESULTS: Among the state TCPs, 42
      reported conducting any retail marketing surveillance, with actual or planned
      STARS use in 34 of these states and in 12 of the 17 states where marketing
      surveillance was not previously reported. Within 6 months of the STARS release,
      21% of surveyed registrants reported using STARS and 35% were likely/very likely
      to use it in the next 6 months. To investigate implementation fidelity, we
      compared data collected by self-trained volunteers and by trained professionals,
      the latter method being more typically in retail marketing surveillance studies.
      Results suggest high or moderate reliability for most STARS measures. CONCLUSION:
      The study concludes with examples of states that used STARS to inform policy
      change.

PMID- 27697951
TI  - 'Sweeter Than a Swisher': amount and themes of little cigar and cigarillo content
      on Twitter.
AB  - OBJECTIVE: Despite recent increases in little cigar and cigarillo (LCC) use
      particularly among urban youth, African-Americans and Latinos-research on
      targeted strategies for marketing these products is sparse. Little is known about
      the amount or content of LCC messages users see or share on social media, a
      popular communication medium among youth and communities of colour. METHODS:
      Keyword rules were used to collect tweets related to LCCs from the Twitter
      Firehose posted in October 2014 and March-April 2015. Tweets were coded for
      promotional content, brand references, co-use with marijuana and subculture
      references (eg, rap/hip-hop, celebrity endorsements) and were classified as
      commercial and 'organic'/non-commercial using a combination of machine learning
      methods, keyword algorithms and human coding. Metadata associated with each tweet
      were used to categorise users as influencers (1000 and more followers) and
      regular users (under 1000 followers). RESULTS: Keyword filters captured over 4
      372 293 LCC tweets. Analyses revealed that 17% of account users posting about
      LCCs were influencers and 1% of accounts were overtly commercial. Influencers
      were more likely to mention LCC brands and post promotional messages.
      Approximately 83% of LCC tweets contained references to marijuana and 29% of
      tweets were memes. Tweets also contained references to rap/hip-hop lyrics and
      urban subculture. CONCLUSIONS: Twitter is a major information-sharing and
      marketing platform for LCCs. Co-use of tobacco and marijuana is common and
      normalised on Twitter. The presence and broad reach of LCC messages on social
      media warrants urgent need for surveillance and serious attention from public
      health professionals and policymakers. Future tobacco use prevention initiatives
      should be adapted to ensure that they are inclusive of LCC use.

PMID- 27697952
TI  - Peer crowd affiliation as a segmentation tool for young adult tobacco use.
AB  - BACKGROUND: In California, young adult tobacco prevention is of prime importance;
      63% of smokers start by the age of 18 years, and 97% start by the age of 26
      years. We examined social affiliation with 'peer crowd' (eg, Hipsters) as an
      innovative way to identify high-risk tobacco users. METHODS: Cross-sectional
      surveys were conducted in 2014 (N=3368) among young adult bar patrons in 3
      California cities. We examined use rates of five products (cigarettes, e
      cigarettes, hookah, cigars and smokeless tobacco) by five race/ethnicity
      categories. Peer crowd affiliation was scored based on respondents' selecting
      pictures of young adults representing those most and least likely to be in their
      friend group. Respondents were classified into categories based on the highest
      score; the peer crowd score was also examined as a continuous predictor. Logistic
      regression models with each tobacco product as the outcome tested the unique
      contribution of peer crowd affiliation, controlling for race/ethnicity, age, sex,
      sexual orientation and city. RESULTS: Respondents affiliating with Hip Hop and
      Hipster peer crowds reported significantly higher rates of tobacco use. As a
      categorical predictor, peer crowd was related to tobacco use, independent of
      associations with race/ethnicity. As a continuous predictor, Hip Hop peer crowd
      affiliation was also associated with tobacco use, and Young Professional
      affiliation was negatively associated, independent of demographic factors.
      CONCLUSIONS: Tobacco product use is not the same across racial/ethnic groups or
      peer crowds, and peer crowd predicts tobacco use independent of race/ethnicity.
      Antitobacco interventions targeting peer crowds may be an effective way to reach
      young adult tobacco users. TRIAL REGISTRATION NUMBER: NCT01686178, Pre-results.

PMID- 27697953
TI  - Long-term e-cigarette use and smoking cessation: a longitudinal study with US
      population.
AB  - BACKGROUND: E-cigarettes have grown popular. The most common pattern is dual use
      with conventional cigarettes. Dual use has raised concerns that it might delay
      quitting of cigarette smoking. This study examined the relationship between long
      term use of e-cigarettes and smoking cessation in a 2-year period. METHODS: A
      nationally representative sample of 2028 US smokers were surveyed in 2012 and
      2014. Long-term e-cigarette use was defined as using e-cigarettes at baseline and
      follow-up. Use of e-cigarettes only at baseline or at follow-up was defined as
      short-term use. Non-users did not use e-cigarettes at either survey. Quit attempt
      rates and cessation rates (abstinent for 3 months or longer) were compared across
      the three groups. RESULTS: At 2-year follow-up, 43.7% of baseline dual users were
      still using e-cigarettes. Long-term e-cigarette users had a higher quit attempt
      rate than short-term or non-users (72.6% vs 53.8% and 45.5%, respectively), and a
      higher cessation rate (42.4% vs 14.2% and 15.6%, respectively). The difference in
      cessation rate between long-term users and non-users remained significant after
      adjusting for baseline variables, OR=4.1 (95% CI 1.5 to 11.4) as did the
      difference between long-term users and short-term users, OR=4.8 (95% CI 1.6 to
      13.9). The difference in cessation rate between short-term users and non-users
      was not significant, OR=0.9 (95% CI 0.5 to 1.4). Among those making a quit
      attempt, use of e-cigarettes as a cessation aid surpassed that of FDA-approved
      pharmacotherapy. CONCLUSIONS: Short-term e-cigarette use was not associated with
      a lower rate of smoking cessation. Long-term use of e-cigarettes was associated
      with a higher rate of quitting smoking.

PMID- 27697955
TI  - Humor promotes learning!

PMID- 27697954
TI  - Traversing the triangulum: the intersection of tobacco, legalised marijuana and
      electronic vaporisers in Denver, Colorado.
AB  - OBJECTIVE: To explore the intersection of tobacco, legalised marijuana and
      electronic vaporiser use among young adults in the 'natural laboratory' of
      Colorado, the first state with legalised retail marijuana. METHODS: We conducted
      semistructured interviews with 32 young adults (18-26 years old) in Denver,
      Colorado, in 2015 to understand the beliefs and practices related to the use of
      tobacco, marijuana and vaporisers. RESULTS: We found ambiguity about whether the
      phrase 'to smoke' refers to the use of tobacco or marijuana products. Smoking
      marijuana blunts (emptied cigarillo or tobacco wrap filled with marijuana) was
      common, but few interpreted this as tobacco use. Marijuana vaporisers were used
      to circumvent public consumption laws (eg, while at work or when driving). Young
      adults considered secondhand tobacco smoke dangerous, but perceived secondhand
      marijuana smoke as benign. DISCUSSION: Using tobacco products as a delivery
      method for marijuana (eg, blunts) might be increasing and normalising tobacco use
      among young adults. Surveillance should explicitly ask about use of tobacco
      products for marijuana. Marijuana vaporisers, often indistinguishable from
      nicotine vaporisers, may be used to circumvent public consumption laws;
      communities concerned about use of marijuana in public spaces should include
      vaporisers (for nicotine or marijuana) in smoke-free regulations. Tobacco,
      marijuana and electronic vaporisers should be studied together, rather than
      separately. This approach is essential in informing research and policy as more
      US states and countries worldwide move to legalise marijuana.

PMID- 27697956
TI  - Team-based learning in large enrollment classes.
AB  - The goal of this review is to highlight the key elements needed to successfully
      deploy team-based learning (TBL) in any class, but especially in large enrolment
      classes, where smooth logistics are essential. The text is based on a lecture and
      workshop given at the American Physiological Society's Institute on Teaching and
      Learning in Madison, WI, in June 2016. After a short overview of the TBL method,
      its underpinning in learning theory, and a summary of current evidence for its
      effectiveness, we present two case studies from our own teaching practices in a
      new medical school. The first case study explores critical elements of design and
      planning for a TBL module, and the second explores best practices in classroom
      management. As medical educators in the fields of physiology, pediatrics,
      nephrology, and family medicine, we present the objective views of subject matter
      experts who adopted TBL as one teaching method rather than TBL experts or
      advocates per se. The review is aimed primarily at faculty contemplating using
      TBL for the first time who are interested in exploring the significant benefits
      and challenges of TBL.

PMID- 27697957
TI  - Systems biology: impressions from a newcomer graduate student in 2016.
AB  - As a newcomer, the philosophical basis of systems biology seems intuitive and
      appealing, the underlying philosophy being that the whole of a living system
      cannot be completely understood by the study of its individual parts. Yet answers
      to the questions "What is systems biology?" and "What constitutes a systems
      biology approach in 2016?" are somewhat more elusive. This seems to be due
      largely to the diversity of disciplines involved and the varying emphasis placed
      on the computational modeling and experimental aspects of systems biology. As
      such, the education of systems biology would benefit from multidisciplinary
      collaboration with both instructors and students from a range of disciplines
      within the same course. This essay is the personal reflection of a graduate
      student trying to get an introductory overview of the field of systems biology
      and some thoughts about effective education of systems biology.

PMID- 27697958
TI  - Faculty and second-year medical student perceptions of active learning in an
      integrated curriculum.
AB  - Patients expect physicians to be lifelong learners who are able to interpret and
      evaluate diagnostic tests, and most medical schools list the development of
      lifelong learning in their program objectives. However, lecture is the most often
      utilized form of teaching in the first two years and is considered passive
      learning. The current generation of medical students has many characteristics
      that should support active learning pedagogies. The purpose of this study was to
      analyze student and faculty perceptions of active learning in an integrated
      medical curriculum at the second-year mark, where students have been exposed to
      multiple educational pedagogies. The first hypothesis of the study was that
      faculty would favor active learning methods. The second hypothesis was that
      Millennial medical students would favor active learning due to their
      characteristics. Primary faculty for years 1 and 2 and second-year medical
      students were recruited for an e-mail survey consisting of 12 questions about
      active learning and lecture. Students perceived that lecture and passive
      pedagogies were more effective for learning, whereas faculty felt active and
      collaborative learning was more effective. Students believed that more content
      should be covered by lecture than faculty. There were also significant
      differences in perceptions of what makes a good teacher. Students and faculty
      both felt that lack of time in the curriculum and preparation time were barriers
      for faculty. The data suggest that students are not familiar with the process of
      learning and that more time may be needed to help students develop lifelong
      learning skills.

PMID- 27697959
TI  - Performance in physiology evaluation: possible improvement by active learning
      strategies.
AB  - The evaluation process is complex and extremely important in the
      teaching/learning process. Evaluations are constantly employed in the classroom
      to assist students in the learning process and to help teachers improve the
      teaching process. The use of active methodologies encourages students to
      participate in the learning process, encourages interaction with their peers, and
      stimulates thinking about physiological mechanisms. This study examined the
      performance of medical students on physiology over four semesters with and
      without active engagement methodologies. Four activities were used: a puzzle, a
      board game, a debate, and a video. The results show that engaging in activities
      with active methodologies before a physiology cognitive monitoring test
      significantly improved student performance compared with not performing the
      activities. We integrate the use of these methodologies with classic lectures,
      and this integration appears to improve the teaching/learning process in the
      discipline of physiology and improves the integration of physiology with
      cardiology and neurology. In addition, students enjoy the activities and perform
      better on their evaluations when they use them.

PMID- 27697960
TI  - Renal clearance: using an interactive activity to visualize a tricky concept.

PMID- 27697961
TI  - Active learning in neuroscience: a manipulative to simulate visual field defects.

PMID- 27697962
TI  - Intrinsic motivation: an overlooked component for student success.

PMID- 27697963
TI  - Shock and awe pedagogy!

PMID- 27697964
TI  - An active learning exercise to facilitate understanding of nephron function:
      anatomy and physiology of renal transporters.

PMID- 27697965
TI  - Simulation for undergraduates: is there a worthy return on investment?

PMID- 27697966
TI  - Technology-Facilitated Sexual Violence Victimization: Results From an Online
      Survey of Australian Adults.
AB  - Online forms of sexual harassment and abuse as experienced by adults represent an
      emerging yet under-researched set of behaviors, such that very few studies have
      sought to estimate the extent of the problem. This article presents the results
      of an online survey of 2,956 Australian adult (aged 18 to 54 years) experiences
      of technology-facilitated sexual violence (TFSV) victimization. The prevalence of
      TFSV was analyzed in relation to a 21-item scale developed in accordance with
      prior conceptual research identifying multiple dimensions of TFSV including
      digital sexual harassment, image-based sexual abuse, sexual aggression and/or
      coercion, and, gender and/or sexuality-based harassment (including virtual sexual
      violence). Results revealed significant differences in lifetime TFSV
      victimization for younger (18-24) and non-heterosexual identifying adults.
      Lifetime TFSV victimization for men and women was not significantly different,
      though women were more likely to report sexual harassment victimization and men
      were more likely to report victimization through the distribution of non
      consensual images, as well as gender and/or sexuality-based harassment. The
      authors conclude that although women and men report experiencing similar overall
      prevalence of TFSV victimization, the nature and impacts of those experiences
      differ in particular gendered ways that reflect broader patterns in both gender
      relations and "offline" sexual harassment.

PMID- 27697968
TI  - SNMMI Leadership Update: SNMMI Mid-Winter Meeting Kicks Off New Year in Phoenix.

PMID- 27697971
TI  - ABNM: MOC Assessment.

PMID- 27697967
TI  - Illness behaviour of general practitioners-a cross-sectional survey.
AB  - BACKGROUND: International guidelines recommend that physicians should be
      registered with a general practitioner (GP) and should avoid self-treatment.
      Adherence to these recommendations is mixed. AIMS: To describe illness behaviour
      and chronic medical conditions of GPs in Germany. METHODS: Cross-sectional,
      observational questionnaire study. We contacted 1000 GPs by mail in April 2014.
      We asked about registration with a GP, chronic conditions and self-treatment. We
      undertook descriptive statistical analysis and analysed associations using t
      tests and chi-square test. RESULTS: Two hundred and eighty-five responses (29%)
      were eligible for analysis. Nineteen per cent of GPs were registered as patients
      of a GP, 58% reported at least one chronic condition, 68% disclosed self
      diagnosis and 60% self-treatment. Self-therapy for chronic conditions was
      inversely correlated with subjective severity of the disease (r = -0.159; P <
      0.05). CONCLUSIONS: The high rates of self-treatment and the low rate of
      registration with a GP of German GPs are in contrast to international guideline
      recommendations. Further research is needed to analyse specific reasons.

PMID- 27697972
TI  - Acute cardiovascular events and all-cause mortality in patients with
      hyperthyroidism: a population-based cohort study.
AB  - OBJECTIVE: Several studies have shown an increased risk for cardiovascular
      disease (CVD) in hyperthyroidism, but most studies have been too small to address
      the effect of hyperthyroidism on individual cardiovascular endpoints. Our main
      aim was to assess the association among hyperthyroidism, acute cardiovascular
      events and mortality. DESIGN: It is a nationwide population-based cohort study.
      Data were obtained from the Danish Civil Registration System and the Danish
      National Patient Registry, which covers all Danish hospitals. We compared the
      rate of all-cause mortality as well as venous thromboembolism (VTE), acute
      myocardial infarction (AMI), ischemic and non-ischemic stroke, arterial embolism,
      atrial fibrillation (AF) and percutaneous coronary intervention (PCI) in the two
      cohorts. Hazard ratios (HR) with 95% confidence intervals (95% CI) were
      estimated. RESULTS: The study included 85 856 hyperthyroid patients and 847 057
      matched population-based controls. Mean follow-up time was 9.2 years. The HR for
      mortality was highest in the first 3 months after diagnosis of hyperthyroidism:
      4.62, 95% CI: 4.40-4.85, and remained elevated during long-term follow-up (>3
      years) (HR: 1.35, 95% CI: 1.33-1.37). The risk for all examined cardiovascular
      events was increased, with the highest risk in the first 3 months after
      hyperthyroidism diagnosis. The 3-month post-diagnosis risk was highest for atrial
      fibrillation (HR: 7.32, 95% CI: 6.58-8.14) and arterial embolism (HR: 6.08, 95%
      CI: 4.30-8.61), but the risks of VTE, AMI, ischemic and non-ischemic stroke and
      PCI were increased also 2- to 3-fold. CONCLUSIONS: We found an increased risk for
      all-cause mortality and acute cardiovascular events in patients with
      hyperthyroidism.

PMID- 27697973
TI  - Crossing the Line.

PMID- 27697974
TI  - A Change of Heart.

PMID- 27697975
TI  - Response to Targeted Therapy in BRAF Mutant Anaplastic Thyroid Cancer.
AB  - Anaplastic thyroid cancer (ATC) is an aggressive uncommon malignancy with limited
      treatment. Traditional antineoplastic chemotherapy has not been successful in the
      management of metastatic ATC. As a result, the focus has shifted to the
      development of novel therapies for this disease. The availability of economical
      comprehensive genomic profiling (CGP) platforms with rapid turn-around to
      identify molecular aberrations in tumors that are potential therapeutic targets
      has increasingly changed the face of cancer therapy. Identification of targetable
      aberrations may help identify novel treatment options for ATC. Herein, we report
      our experience with a 47-year-old patient with metastatic ATC who experienced
      recurrent, progressive disease and rapid clinical deterioration despite surgery,
      radiation therapy, and treatment with 2 different chemotherapy regimens. She was
      found to have a BRAF V600E mutation on CGP, and was started on targeted therapy
      with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib. After 2
      months of treatment, she showed a clinical and radiologic response. The patient
      remained on this combination for 9 months until evidence of disease progression.
      Discontinuation of these drugs was associated with rapid tumor growth. Through
      this case we want to emphasize the importance of early molecular sequencing and
      identification of genetic aberrations in patients with ATC, and using that
      information to develop therapies for ATC, an aggressive malignancy with limited
      therapy and a poor outcome.

PMID- 27697977
TI  - Emerging Issues and Opportunities in Health Information Technology.
AB  - When used effectively, health information technology (HIT) can transform clinical
      care and contribute to new research discoveries. Despite advances in HIT and
      increased electronic health record adoption, many challenges to optimal use,
      interoperability, and data sharing exist. Data standardization across systems is
      limited, and scanned medical note documents result in unstructured data that make
      reporting on quality measures for reimbursement burdensome. Different policies
      and initiatives, including the Health Information Technology for Economic and
      Clinical Health Act, the Medicare Access and CHIP Reauthorization Act, and the
      National Cancer Moonshot initiative, among others, all recognize the impact that
      HIT can have on cancer care. Given the growing role HIT plays in health care, it
      is vital to have effective and efficient HIT systems that can exchange
      information, collect credible data that is analyzable at the point of care, and
      improves the patient-provider relationship. In June 2016, NCCN hosted the
      Emerging Issues and Opportunities in Health Information Technology Policy Summit.
      The summit addressed challenges, issues, and opportunities in HIT as they relate
      to cancer care. Keynote presentations and panelists discussed moving beyond
      Meaningful Use, HIT readiness to support and report on quality care, the role of
      HIT in precision medicine, the role of HIT in the National Cancer Moonshot
      initiative, and leveraging HIT to improve quality of clinical care.

PMID- 27697978
TI  - Practice Patterns in the Diagnosis and Treatment of Polycythemia Vera in the Post
      JAK2 V617F Discovery Era.
AB  - Polycythemia vera (PV) is an acquired clonal hematopoietic stem cell disorder
      characterized by an overproduction of red blood cells, white blood cells, and
      platelets; thrombotic and hemorrhagic complications; and an increased risk of
      transformation to myelofibrosis and acute leukemia. In 1967, the Polycythemia
      Vera Study Group proposed the optimal approach to diagnosis and treatment of PV,
      and in 2002, investigators from Johns Hopkins University School of Medicine
      surveyed the practice patterns of hematologists as they pertained to PV. Since
      this survey, the JAK2 V617F mutation was discovered, leading to a new era of
      discovery in the disease pathogenesis, diagnosis, and classification and
      treatment of PV. Our objective was to survey hematologists in the diagnosis and
      treatment of PV in the modern, post-JAK2 V617F discovery era. An anonymous 17
      question survey was emailed to members of the Myeloproliferative Neoplasm (MPN)
      Research Foundation database and Aplastic Anemia and MDS International
      Foundation. A total of 71 surveys were used in the analysis. Diagnostic testing
      varied according to the respondent's clinical experience and practice type. In
      addition, there were marked differences in target hematocrit and platelet count
      among those surveyed. There continue to be variations in diagnosis and treatment
      of PV despite WHO guidelines and the JAK2 discovery. US-based guidelines for MPNs
      are needed to create consistency in the management of PV and other MPNs.

PMID- 27697976
TI  - NCCN Guidelines Insights: Bladder Cancer, Version 2.2016.
AB  - These NCCN Guidelines Insights discuss the major recent updates to the NCCN
      Guidelines for Bladder Cancer based on the review of the evidence in conjunction
      with the expert opinion of the panel. Recent updates include (1) refining the
      recommendation of intravesical bacillus Calmette-Guerin, (2) strengthening the
      recommendations for perioperative systemic chemotherapy, and (3) incorporating
      immunotherapy into second-line therapy for locally advanced or metastatic
      disease. These NCCN Guidelines Insights further discuss factors that affect
      integration of these recommendations into clinical practice.

PMID- 27697979
TI  - Merkel Cell Carcinoma: A Population Analysis on Survival.
AB  - PURPOSE: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy.
      However, factors associated with disease presentation and outcomes remain
      uncertain, especially in light of recent changes in workup, such as sentinel
      lymph node biopsy. Therefore, this study used the SEER database to examine
      factors that could affect stage at presentation and treatment. METHODS: We
      identified 4,543 patients and evaluated associations between sex, race, age,
      primary disease site, disease presentation, and treatment. We also used
      univariate and multivariate analyses to examine the effect of these factors on
      disease-specific survival (DSS) and overall survival (OS). We specifically
      conducted subgroup analyses on a more modern cohort of patients with MCC treated
      between 2006 and 2012. RESULTS: Male sex, older age, larger tumor size, and
      primary tumors of the scalp, neck, or trunk were associated with a higher burden
      of nodal disease. Multivariate predictors of worse DSS/OS in both the recent and
      overall cohort included age older than 75 years, number of lymph nodes involved,
      tumors greater than 5 cm, metastatic disease, or lack of radiation therapy. The
      number of involved nodes was the best predictor of DSS/OS. Associations with
      radiation therapy were most pronounced in patients with nodal disease and those
      not undergoing surgery. CONCLUSIONS: Sex, age, tumor size, and primary site of
      disease correlated with burden of nodal disease in MCC. Associations between
      disease presentation and treatment strategies such as radiation and DSS and OS
      have remained relatively constant in the modern era from 2006 to 2012 compared
      with findings from prior studies.

PMID- 27697980
TI  - Effects of a Provincial-Wide Implementation of Screening for Distress on
      Healthcare Professionals' Confidence and Understanding of Person-Centered Care in
      Oncology.
AB  - BACKGROUND: Although published studies report that screening for distress (SFD)
      improves the quality of care for patients with cancer, little is known about how
      SFD impacts healthcare professionals (HCPs). OBJECTIVES: This quality improvement
      project examined the impact of implementing the SFD intervention on HCPs'
      confidence in addressing patient distress and awareness of person-centered care.
      PATIENTS AND METHODS: This project involved pre-evaluation and post-evaluation of
      the impact of implementing SFD. A total of 254 HCPs (cohort 1) were recruited
      from 17 facilities across the province to complete questionnaires. SFD was then
      implemented at all cancer care facilities over a 10-month implementation period,
      after which 157 HCPs (cohort 2) completed post-implementation questionnaires. At
      regional and community care centers, navigators supported the integration of SFD
      into routine practice; therefore, the impact of navigators was examined. RESULTS:
      HCPs in cohort 2 reported significantly greater confidence in managing patients'
      distress and greater awareness about person-centered care relative to HCPs in
      cohort 1. HCPs at regional and community sites reported greater awareness in
      person-centeredness before and after the intervention, and reported fewer
      negative impacts of SFD relative to HCPs at tertiary sites. Caring for single or
      multiple tumor types was an effect modifier, with effects observed only in the
      HCPs treating multiple tumors. CONCLUSIONS: Implementation of SFD was beneficial
      for HCPs' confidence and awareness of person-centeredness. Factors comprising
      different models of care, such as having site-based navigators and caring for
      single or multiple tumors, influenced outcomes.

PMID- 27697981
TI  - High Body Mass Index in Elderly Patients With DLBCL Treated With Rituximab
      Containing Therapy Compensates for Negative Impact of Male Sex.
AB  - BACKGROUND: The impact of patient body habitus and sex on outcomes in diffuse
      large B-cell lymphoma (DLBCL) remains controversial. We investigated the impact
      of body mass index (BMI), body surface area (BSA), age, and sex on clinical
      outcomes in patients with DLBCL treated in the rituximab era. PATIENTS AND
      METHODS: Patients with de novo DLBCL (n=1,386) diagnosed between June 2000 and
      December 2010 treated with rituximab-containing chemotherapy were identified from
      the NCCN Oncology Outcomes Database for Non-Hodgkin's Lymphoma. Progression-free
      survival (PFS) and overall survival (OS) at 3 years were analyzed based on sex,
      age, and baseline BMI/BSA. RESULTS: High BMI was associated with a lower risk of
      disease progression or death than low or normal BMI, whereas male sex was
      associated with poor clinical outcomes, especially among elderly patients (age
      >60 years). Compared with elderly women, elderly men experienced worse PFS (3
      year hazard ratio [HR], 1.5) and OS (3-year HR, 1.6), but these differences
      diminished with increases in BMI and BSA. In multivariable analysis, normal BMI
      compared with high BMI was independently associated with poor outcomes (3-year
      PFS HR, 1.5; OS HR, 1.6) after adjusting for sex. Notably, only 13% of elderly
      men had BMI less than 25 kg/m2 and only 26% had BSA less than 2 m2 CONCLUSIONS:
      Analysis of unselected patients with DLBCL treated with rituximab-containing
      chemotherapy confirmed an age-dependent disadvantage to male sex in treatment
      outcomes, but this effect is abrogated by higher levels of BMI and BSA in most
      North American men.

PMID- 27697982
TI  - Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology.
AB  - Gastric cancer is the fifth most frequently diagnosed cancer and the third
      leading cause of death from cancer in the world. Several advances have been made
      in the staging procedures, imaging techniques, and treatment approaches. The NCCN
      Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer
      provide an evidence- and consensus-based treatment approach for the management of
      patients with gastric cancer. This manuscript discusses the recommendations
      outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression,
      systemic therapy for locally advanced or metastatic disease, and best supportive
      care for the prevention and management of symptoms due to advanced disease.

PMID- 27697983
TI  - Advances in Systemic Therapy for Metastatic or Advanced Gastric Cancer.
AB  - In recent years, various new agents have been investigated for the treatment of
      advanced gastric cancer (AGC). The anti-HER2 antibody trastuzumab has been shown
      to prolong the overall survival of patients with HER2-positive AGC and has become
      a standard treatment. However, lapatinib, or ado-trastuzumab emtansine (T-DM1),
      did not show survival benefit in AGC, although it has shown remarkable efficacy
      for HER2-positive breast cancer. The efficacy of the anti-vascular endothelial
      growth factor receptor monoclonal antibody ramucirumab for pretreated gastric
      cancer is a milestone for antiangiogenic therapy for AGC. Early clinical trials
      of TAS-118, TAS-102, and STAT3 inhibitors; IMAB362 (anti-Claudin 18.2); and
      immune checkpoint inhibitors are all encouraging. These findings warrant further
      evaluation in larger clinical trials.

PMID- 27697984
TI  - Multimodality Therapy of Localized Gastric Adenocarcinoma.
AB  - Surgical resection is the primary method of obtaining a potential cure for
      patients with gastric adenocarcinoma. However, chemotherapy or chemoradiotherapy
      offer significant improvement in survival over surgery alone. Much of the
      difficulty in deciding the optimal treatment strategy is choosing between
      perioperative chemotherapy or adjuvant chemoradiotherapy. Adding to the
      complexity is the potential for incorporating treatment strategies based on
      clinical trials performed in Asia. There is likely a difference in tumor biology
      between Eastern and Western patients with gastric adenocarcinoma, in addition to
      the clear differences in screening, pathologic assessment, and surgical
      technique. Even among tumors in Western populations, heterogeneity of histology,
      anatomy, and staging among studies make cross-trial comparisons difficult. There
      is also active controversy surrounding the staging and management of
      gastroesophageal junction tumors. Lastly, the benefit of extended lymph node
      dissection is not clear based on the existing studies and has not been firmly
      established as a surgical standard of care for all patients. Future goals include
      better classification of gastric cancer, continued pursuit of randomized trials
      in Western populations, standardization of surgical technique, and incorporation
      of targeted therapies.

PMID- 27697985
TI  - Ambulatory Oncology Operations: Strategies to Alleviate Complexity.

PMID- 27697990
TI  - AACR Cancer Progress Report 2016: Improving Lives Through Research.

PMID- 27697987
TI  - Neural correlates of three types of negative life events during angry face
      processing in adolescents.
AB  - Negative life events (NLE) contribute to anxiety and depression disorders, but
      their relationship with brain functioning in adolescence has rarely been studied.
      We hypothesized that neural response to social threat would relate to NLE in the
      frontal-limbic emotional regions. Participants (N = 685) were drawn from the
      Imagen database of 14-year-old community adolescents recruited in schools. They
      underwent functional MRI while viewing angry and neutral faces, as a probe to
      neural response to social threat. Lifetime NLEs were assessed using the
      'distress', 'family' and 'accident' subscales from a life event dimensional
      questionnaire. Relationships between NLE subscale scores and neural response were
      investigated. Links of NLE subscales scores with anxiety or depression outcomes
      at the age of 16 years were also investigated. Lifetime 'distress' positively
      correlated with ventral-lateral orbitofrontal and temporal cortex activations
      during angry face processing. 'Distress' scores correlated with the probabilities
      of meeting criteria for Generalized Anxiety Disorder or Major Depressive Disorder
      at the age of 16 years. Lifetime 'family' and 'accident' scores did not relate
      with neural response or follow-up conditions, however. Thus, different types of
      NLEs differentially predicted neural responses to threat during adolescence, and
      differentially predicted a de novo internalizing condition 2 years later. The
      deleterious effect of self-referential NLEs is suggested.

PMID- 27697992
TI  - FCGR, Cetuximab, and Colorectal Cancer Survival-Letter.

PMID- 27697991
TI  - Dual Characteristics of Novel HER2 Kinase Domain Mutations in Response to HER2
      Targeted Therapies in Human Breast Cancer.
AB  - PURPOSE: Somatic mutations in the tyrosine kinase domain of human epidermal
      growth factor receptor 2 (HER2) may be an alternative mechanism to HER2
      activation and can affect the sensitivity toward HER2-targeted therapies. We
      aimed to investigate the prevalence, clinicopathologic characteristics, and
      functional relevance of novel HER2 mutations in breast cancer. EXPERIMENTAL
      DESIGN: We performed Sanger sequencing of all exons of the HER2 gene in 1,248
      primary tumors and 18 paired metastatic samples. Novel HER2 mutations were
      functionally characterized. RESULTS: The total HER2 somatic mutation rate was
      2.24% (28/1,248). Of the seven novel HER2 mutations, L768S and V773L were only
      detected in HER2-negative tumors, whereas K753E was found in HER2-positive
      disease. L768S and V773L mutations exhibited a significant increase in tyrosine
      kinase-specific activity and strongly increased the phosphorylation of signaling
      proteins in various cell lines. Xenograft experiments showed that NIH3T3 cells
      bearing the L768S and V773L mutations displayed more rapid growth. MCF10A, BT474,
      and MDA-MB-231 cells bearing the K753E mutation were resistant to lapatinib, but
      could be inhibited by neratinib. Finally, comparison of HER2 mutations in 18
      pairs of primary and metastatic lesions revealed that the drug-resistant HER2
      mutations (K753E and L755S) were enriched in metastatic lesions. CONCLUSIONS:
      HER2-negative breast cancer with activating mutations can benefit from HER2
      targeted therapies. Meanwhile, mutations in the HER2 kinase domain might be a key
      mechanism of resistance to HER2-targeted therapy, and irreversible tyrosine
      kinase inhibitors such as neratinib may offer alternative treatment options. Clin
      Cancer Res; 22(19); 4859-69. (c)2016 AACR.

PMID- 27697993
TI  - Retraction: Synergistic Interactions between Vorinostat and Sorafenib in Chronic
      Myelogenous Leukemia Cells Involve Mcl-1 and p21CIP1 Down-Regulation.

PMID- 27697995
TI  - Immunotherapy in Endometrial Cancer: In the Nick of Time.
AB  - Immunotherapy with checkpoint inhibitors is changing the face of oncology
      treatments for many tumors, and endometrial carcinoma may not be an exception.
      Several endometrial cancer groups from the molecular taxonomy are characterized
      by having an ultramutated/hypermutated genome, which could be the first Achilles'
      heel identified in this malignancy in decades. Clin Cancer Res; 22(23); 5623-5.
      (c)2016 AACRSee related article by Santin et al., p. 5682.

PMID- 27697994
TI  - The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and
      Microenvironmental Signaling in Chronic Lymphocytic Leukemia.
AB  - Purpose: B-cell receptor (BCR)-associated kinase inhibitors, such as ibrutinib,
      have revolutionized the treatment of chronic lymphocytic leukemia (CLL). However,
      these agents are not curative, and resistance is already emerging in a proportion
      of patients. IL4, expressed in CLL lymph nodes, can augment BCR signaling and
      reduce the effectiveness of BCR kinase inhibitors. Therefore, simultaneous
      targeting of the IL4- and BCR signaling pathways by cerdulatinib, a novel dual
      Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve
      treatment responses in patients.Experimental Design: PBMCs from patients with CLL
      were treated in vitro with cerdulatinib alone or in combination with venetoclax.
      Cell death, chemokine, and cell signaling assay were performed and analyzed by
      flow cytometry, immunoblotting, q-PCR, and ELISA as indicated.Results: At
      concentrations achievable in patients, cerdulatinib inhibited BCR- and IL4
      induced downstream signaling in CLL cells using multiple readouts and prevented
      anti-IgM- and nurse-like cell (NLC)-mediated CCL3/CCL4 production. Cerdulatinib
      induced apoptosis of CLL cells, in a time- and concentration-dependent manner,
      and particularly in IGHV-unmutated samples with greater BCR signaling capacity
      and response to IL4, or samples expressing higher levels of sIgM, CD49d+, or
      ZAP70+ Cerdulatinib overcame anti-IgM, IL4/CD40L, or NLC-mediated protection by
      preventing upregulation of MCL-1 and BCL-XL; however, BCL-2 expression was
      unaffected. Furthermore, in samples treated with IL4/CD40L, cerdulatinib
      synergized with venetoclax in vitro to induce greater apoptosis than either drug
      alone.Conclusions: Cerdulatinib is a promising therapeutic for the treatment of
      CLL either alone or in combination with venetoclax, with the potential to target
      critical survival pathways in this currently incurable disease. Clin Cancer Res;
      23(9); 2313-24. (c)2016 AACR.

PMID- 27697996
TI  - Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal
      Cancer.
AB  - Purpose: Gut microbiota have been implicated in the development of colorectal
      cancer. We evaluated the utility of fecal bacterial marker candidates identified
      by our metagenome sequencing analysis for colorectal cancer
      diagnosis.Experimental Design: Subjects (total 439; 203 colorectal cancer and 236
      healthy subjects) from two independent Asian cohorts were included. Probe-based
      duplex quantitative PCR (qPCR) assays were established for the quantification of
      bacterial marker candidates.Results: Candidates identified by metagenome
      sequencing, including Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc),
      Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), and one undefined
      species (labeled as m7), were examined in fecal samples of 203 colorectal cancer
      patients and 236 healthy controls by duplex-qPCR. Strong positive correlations
      were demonstrated between the quantification of each candidate by our qPCR assays
      and metagenomics approach (r = 0.801-0.934, all P < 0.0001). Fn was significantly
      more abundant in colorectal cancer than controls (P < 0.0001), with AUROC of
      0.868 (P < 0.0001). At the best cut-off value maximizing sum of sensitivity and
      specificity, Fn discriminated colorectal cancer from controls with a sensitivity
      of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of
      four bacteria (Fn + Ch + m7-Bc) showed an improved diagnostic ability compared
      with Fn alone (AUROC = 0.886, P < 0.0001) in cohort I. These findings were
      further confirmed in an independent cohort II. In particular, improved diagnostic
      performances of Fn alone (sensitivity 92.8%, specificity 79.8%) and four bacteria
      (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal
      immunochemical testing for the detection of colorectal cancer.Conclusions: Stool
      based colorectal cancer-associated bacteria can serve as novel noninvasive
      diagnostic biomarkers for colorectal cancer. Clin Cancer Res; 23(8); 2061-70.
      (c)2016 AACR.

PMID- 27697997
TI  - Plerixafor Improves Primary Tumor Response and Reduces Metastases in Cervical
      Cancer Treated with Radio-Chemotherapy.
AB  - Purpose: There is an important need to improve the effectiveness of radio
      chemotherapy (RTCT) for cervical cancer. The CXCL12/CXCR4 pathway can influence
      RT response by recruiting normal myeloid cells to the tumor microenvironment that
      in turn can exert radioprotective effects, and may promote metastases. The
      objective of this study was to explore the efficacy and toxicity of combining
      RTCT with CXCL12/CXCR4 inhibition in cervical cancer.Experimental Design: CXCR4
      expression was measured in 115 patients with cervical cancer. Two primary
      orthotopic cervical cancer xenografts (OCICx) with different levels of CXCR4
      expression were treated with RT (30 Gy: 15 daily fractions) and weekly cisplatin
      (4 mg/kg), with or without the CXCR4 inhibitor Plerixafor (5 mg/kg/day). The
      endpoints were tumor growth delay and lymph node metastases. Acute intestinal
      toxicity was assessed using a crypt cell assay.Results: There was a fivefold
      variation in CXCR4 mRNA expression in the patient samples, and good correlation
      between the expression in patients and in the xenografts. The combination of RTCT
      and Plerixafor produced substantial tumor growth delay and reduced lymph node
      metastases compared with RTCT alone in both of the xenograft models. There was a
      trend toward reduced acute intestinal toxicity with the addition of Plerixafor to
      RTCT. There were no changes in normal organ morphology to suggest increased late
      toxicity.Conclusions: This study demonstrates that the addition of Plerixafor to
      standard RTCT improves primary tumor response and reduces metastases in cervical
      cancer with no increase in toxicity. This combination warrants further
      investigation in phase I/II clinical trials. Clin Cancer Res; 23(5); 1242-9.
      (c)2016 AACR.

PMID- 27697998
TI  - Targeting Hypoxic Prostate Tumors Using the Novel Hypoxia-Activated Prodrug
      OCT1002 Inhibits Expression of Genes Associated with Malignant Progression.
AB  - Purpose: To understand the role of hypoxia in prostate tumor progression and to
      evaluate the ability of the novel unidirectional hypoxia-activated prodrug
      OCT1002 to enhance the antitumor effect of bicalutamide.Experimental Design: The
      effect of OCT1002 on prostate cancer cells (LNCaP, 22Rv1, and PC3) was measured
      in normoxia and hypoxia in vitroIn vivo, tumor growth and lung metastases were
      measured in mice treated with bicalutamide, OCT1002, or a combination. Dorsal
      skin fold chambers were used to image tumor vasculature in vivo Longitudinal gene
      expression changes in tumors were analyzed using PCR.Results: Reduction of
      OCT1002 to its active form (OCT1001) decreased prostate cancer cell viability. In
      LNCaP-luc spheroids, OCT1002 caused increased apoptosis and decreased
      clonogenicity. In vivo, treatment with OCT1002 alone, or with bicalutamide,
      showed significantly greater tumor growth control and reduced lung metastases
      compared with controls. Reestablishment of the tumor microvasculature following
      bicalutamide-induced vascular collapse is inhibited by OCT1002. Significantly,
      the upregulation of RUNX2 and its targets caused by bicalutamide alone was
      blocked by OCT1002.Conclusions: OCT1002 selectively targets hypoxic tumor cells
      and enhances the antitumor efficacy of bicalutamide. Furthermore, bicalutamide
      caused changes in gene expression, which indicated progression to a more
      malignant genotype; OCT1002 blocked these effects, emphasizing that more
      attention should be attached to understanding genetic changes that may occur
      during treatment. Early targeting of hypoxic cells with OCT1002 can provide a
      means of inhibiting prostate tumor growth and malignant progression. This is of
      importance for the design and refinement of existing androgen-deprivation
      regimens in the clinic. Clin Cancer Res; 23(7); 1797-808. (c)2016 AACR.

PMID- 27697999
TI  - The Sphingosine-1-Phosphate Modulator FTY720 Targets Multiple Myeloma via the
      CXCR4/CXCL12 Pathway.
AB  - Purpose: To explore the functional consequences of possible cross-talk between
      the CXCR4/CXCL12 and the sphingosine-1-phosphate (S1P) pathways in multiple
      myeloma (MM) cells and to evaluate the effect of S1P targeting with the FTY720
      modulator as a potential anti-MM therapeutic strategy.Experimental Design and
      Results: S1P targeting with FTY720 induces MM cell apoptosis. The combination of
      FTY720 with the SPHK1 inhibitor SKI-II results in synergistic inhibition of MM
      growth. CXCR4/CXCL12-enhanced expression correlates with reduced MM cell
      sensitivity to both FTY720 and SKI-II inhibitors, and with SPHK1 coexpression in
      both cell lines and primary MM bone marrow (BM) samples, suggesting regulative
      cross-talk between the CXCR4/CXCL12 and SPHK1 pathways in MM cells. FTY720 was
      found to directly target CXCR4. FTY720 profoundly reduces CXCR4 cell-surface
      levels and abrogates the CXCR4-mediated functions of migration toward CXCL12 and
      signaling pathway activation. Moreover, FTY720 cooperates with bortezomib,
      inducing its cytotoxic activity and abrogating the bortezomib-mediated increase
      in CXCR4 expression. FTY720 effectively targets bortezomib-resistant cells and
      increases their sensitivity to bortezomib, promoting DNA damage. Finally, in a
      recently developed novel xenograft model of CXCR4-dependent systemic MM with BM
      involvement, FTY720 treatment effectively reduces tumor burden in the BM of MM
      bearing mice. FTY720 in combination with bortezomib demonstrates superior tumor
      growth inhibition and abrogates bortezomib-induced CXCR4 increase on MM
      cells.Conclusions: Altogether, our work identifies a cross-talk between the S1P
      and CXCR4 pathways in MM cells and provides a preclinical rationale for the
      therapeutic application of FTY720 in combination with bortezomib in patients with
      MM. Clin Cancer Res; 23(7); 1733-47. (c)2016 AACR.

PMID- 27698001
TI  - Assessment of Total Lesion Glycolysis by 18F FDG PET/CT Significantly Improves
      Prognostic Value of GEP and ISS in Myeloma.
AB  - Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography with CT
      attenuation correction (18F-FDG PET/CT) is useful in the detection and
      enumeration of focal lesions and in semiquantitative characterization of
      metabolic activity (glycolytic phenotype) by calculation of glucose uptake. Total
      lesion glycolysis (TLG) and metabolic tumor volume (MTV) have the potential to
      improve the value of this approach and enhance the prognostic value of disease
      burden measures. This study aims to determine whether TLG and MTV are associated
      with progression-free survival (PFS) and overall survival (OS), and whether they
      improve risk assessments such as International Staging System (ISS) stage and
      GEP70 risk.Experimental Design: 192 patients underwent whole body PET/CT in the
      Total Therapy 3A (TT3A) trial and were evaluated using three-dimensional region
      of-interest analysis with TLG, MTV, and standard measurement parameters derived
      for all focal lesions with peak SUV above the background red marrow
      signal.Results: In multivariate analysis, baseline TLG > 620 g and MTV > 210 cm3
      remained a significant factor of poor PFS and OS after adjusting for baseline
      myeloma variables. Combined with the GEP70 risk score, TLG > 205 g identifies a
      high-risk-behaving subgroup with poor expected survival. In addition, TLG > 205 g
      accurately divides ISS stage II patients into two subgroups with similar outcomes
      to ISS stage I and ISS stage III, respectively.Conclusions: TLG and MTV have
      significant survival implications at baseline and offer a more precise
      quantitation of the glycolytic phenotype of active disease. These measures can be
      assessed more readily than before using FDA-approved software and should be
      standardized and incorporated into clinical trials moving forward. Clin Cancer
      Res; 23(8); 1981-7. (c)2016 AACR.

PMID- 27698000
TI  - Genomic Approaches to Understanding Response and Resistance to Immunotherapy.
AB  - Immunotherapy has led to a paradigm shift in the treatment of some malignancies,
      providing long-term, durable responses for patients with advanced cancers.
      However, such therapy has benefited only a subset of patients, with some patients
      failing to respond to treatment at all and others achieving a limited response
      followed by tumor progression. Understanding factors contributing to an effective
      response and further elucidating mechanisms of resistance will be crucial as
      these therapies are applied more broadly. Genomics-based approaches have
      significantly advanced the study of response and resistance to immunotherapy in
      general, and to immune checkpoint blockade more specifically. Here, we review how
      genomic and transcriptomic approaches have identified both somatic and germline
      positive correlates of response, including high mutational/neoantigen load and
      low intratumoral heterogeneity, among others. The genomic analysis of resistant
      tumors has additionally identified crucial factors involved in resistance to
      immune checkpoint blockade, including loss of PTEN and upregulation of other
      immune checkpoints. Overall, the continued use of genomic techniques at the point
      of care, combined with appropriate functional studies, would ideally lead to a
      better understanding of why certain patients respond to immune-based therapies,
      allowing clinicians to identify the subset of patients likely to benefit from
      such therapy, and potentially providing insight into how other therapies may be
      added in combination to increase the number of patients who may benefit from
      immunotherapy. Clin Cancer Res; 22(23); 5642-50. (c)2016 AACR.

PMID- 27698002
TI  - TNFalpha-Induced Mucin 4 Expression Elicits Trastuzumab Resistance in HER2
      Positive Breast Cancer.
AB  - PURPOSE: Although trastuzumab administration improved the outcome of HER2
      positive breast cancer patients, resistance events hamper its clinical benefits.
      We demonstrated that TNFalpha stimulation in vitro induces trastuzumab resistance
      in HER2-positive breast cancer cell lines. Here, we explored the mechanism of
      TNFalpha-induced trastuzumab resistance and the therapeutic strategies to
      overcome it. EXPERIMENTAL DESIGN: Trastuzumab-sensitive breast cancer cells,
      genetically engineered to stably overexpress TNFalpha, and de novo trastuzumab
      resistant tumors, were used to evaluate trastuzumab response and TNFalpha
      blocking antibodies effectiveness respectively. Immunohistochemistry and antibody
      dependent cell cytotoxicity (ADCC), together with siRNA strategy, were used to
      explore TNFalpha influence on the expression and function of its downstream
      target, mucin 4 (MUC4). The clinical relevance of MUC4 expression was studied in
      a cohort of 78 HER2-positive breast cancer patients treated with adjuvant
      trastuzumab. RESULTS: TNFalpha overexpression turned trastuzumab-sensitive cells
      and tumors into resistant ones. Histopathologic findings revealed mucin foci in
      TNFalpha-producing tumors. TNFalpha induced upregulation of MUC4 that reduced
      trastuzumab binding to its epitope and impaired ADCC. Silencing MUC4 enhanced
      trastuzumab binding, increased ADCC, and overcame trastuzumab and trastuzumab
      emtansine antiproliferative effects in TNFalpha-overexpressing cells.
      Accordingly, administration of TNFalpha-blocking antibodies downregulated MUC4
      and sensitized de novo trastuzumab-resistant breast cancer cells and tumors to
      trastuzumab. In HER2-positive breast cancer samples, MUC4 expression was found to
      be an independent predictor of poor disease-free survival (P = 0.008).
      CONCLUSIONS: We identified TNFalpha-induced MUC4 expression as a novel
      trastuzumab resistance mechanism. We propose MUC4 expression as a predictive
      biomarker of trastuzumab efficacy and a guide to combination therapy of TNFalpha
      blocking antibodies with trastuzumab. Clin Cancer Res; 23(3); 636-48. (c)2016
      AACR.

PMID- 27698003
TI  - Estimation of Survival Probabilities for Use in Cost-effectiveness Analyses: A
      Comparison of a Multi-state Modeling Survival Analysis Approach with Partitioned
      Survival and Markov Decision-Analytic Modeling.
AB  - Modeling of clinical-effectiveness in a cost-effectiveness analysis typically
      involves some form of partitioned survival or Markov decision-analytic modeling.
      The health states progression-free, progression and death and the transitions
      between them are frequently of interest. With partitioned survival, progression
      is not modeled directly as a state; instead, time in that state is derived from
      the difference in area between the overall survival and the progression-free
      survival curves. With Markov decision-analytic modeling, a priori assumptions are
      often made with regard to the transitions rather than using the individual
      patient data directly to model them. This article compares a multi-state modeling
      survival regression approach to these two common methods. As a case study, we use
      a trial comparing rituximab in combination with fludarabine and cyclophosphamide
      v. fludarabine and cyclophosphamide alone for the first-line treatment of chronic
      lymphocytic leukemia. We calculated mean Life Years and QALYs that involved
      extrapolation of survival outcomes in the trial. We adapted an existing multi
      state modeling approach to incorporate parametric distributions for transition
      hazards, to allow extrapolation. The comparison showed that, due to the different
      assumptions used in the different approaches, a discrepancy in results was
      evident. The partitioned survival and Markov decision-analytic modeling deemed
      the treatment cost-effective with ICERs of just over L16,000 and L13,000,
      respectively. However, the results with the multi-state modeling were less
      conclusive, with an ICER of just over L29,000. This work has illustrated that it
      is imperative to check whether assumptions are realistic, as different model
      choices can influence clinical and cost-effectiveness results.

PMID- 27698004
TI  - Effects of Nurses' Perceptions of Actual and Demanded Competence on Turnover
      Intentions.
AB  - With the growing focus on continuous professional development, demands placed on
      nurses to uphold nursing competence have been increasing. This study examined how
      nurses with different lengths of clinical experience perceived the relationship
      between their actual competence and the competence they felt was demanded of
      them, and how this relationship was related to their turnover intentions. Survey
      questionnaires were distributed to 1,377 nurses, of whom 765 returned usable
      completed forms. The results showed that across all the groups of clinical
      experience, nurses perceived the demanded competence levels to be higher than
      their actual competence levels. However, turnover intentions were not related to
      nurses' perceptions of demanded competence and were negatively related to
      perceptions of actual competence. The levels of competence demanded should not be
      considered as threats for nurses. Improving nurses' competence may reduce their
      turnover intentions.

PMID- 27698006
TI  - The Authors Reply.

PMID- 27698007
TI  - RE: "SEVERE HUMAN PARECHOVIRUS INFECTIONS IN INFANTS AND THE ROLE OF OLDER
      SIBLINGS".

PMID- 27698008
TI  - Phlebitis as a consequence of peripheral intravenous administration of
      cisatracurium besylate in critically ill patients.
AB  - This case report series describes 3 cases of cisatracurium besylate associated
      phlebitis after an infusion period of 14-20 hours. No similar cases have been
      reported in the literature. Association of phlebitis with another neuromuscular
      blocking agent, atracurium, has been described in the literature. The acidity of
      atracurium is thought to be the main cause. It is recommended that atracurium is
      administered only via central venous catheters when indicated to infuse over
      prolonged periods of time due to the acidity. Cisatracurium is a stereoisomer of
      atracurium and as such has the same molecular weight. Although cisatracurium also
      has a similar acidity as atracurium, a recommendation concerning infusion via a
      central venous catheter is lacking. We suggest prolonged administration of
      cisatracurium besylate only via centrally placed venous catheters or if not
      possible to careful monitor relevant peripheral intravenous sites to diminish the
      risks of phlebitis and associated complications or other cutaneous reactions.

PMID- 27698005
TI  - Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case
      Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed
      Genetic Loci.
AB  - Previously developed models for predicting absolute risk of invasive epithelial
      ovarian cancer have included a limited number of risk factors and have had low
      discriminatory power (area under the receiver operating characteristic curve
      (AUC) < 0.60). Because of this, we developed and internally validated a relative
      risk prediction model that incorporates 17 established epidemiologic risk factors
      and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data
      from 11 case-control studies in the United States (5,793 cases; 9,512 controls)
      from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010).
      We developed a hierarchical logistic regression model for predicting case-control
      status that included imputation of missing data. We randomly divided the data
      into an 80% training sample and used the remaining 20% for model evaluation. The
      AUC for the full model was 0.664. A reduced model without SNPs performed
      similarly (AUC = 0.649). Both models performed better than a baseline model that
      included age and study site only (AUC = 0.563). The best predictive power was
      obtained in the full model among women younger than 50 years of age (AUC =
      0.714); however, the addition of SNPs increased the AUC the most for women older
      than 50 years of age (AUC = 0.638 vs. 0.616). Adapting this improved model to
      estimate absolute risk and evaluating it in prospective data sets is warranted.

PMID- 27698009
TI  - Acute eosinophilic pneumonia masquerading as multiple pulmonary embolisms.
AB  - A 47-year-old previously healthy man was admitted to the hospital with a 5-day
      history of fever, dry cough, and dyspnoea. Thoracic radiographs and CT scan
      showed extensive bilateral consolidation predominantly involving the central
      portions of the upper lung lobes, along with multiple scattered nodules. On
      taking a thorough history, it was found that the patient had visited a gritty 100
      year-old Japanese folk house 1 week ago. An urgent bronchoscopy was performed,
      and the results were consistent with the findings of acute eosinophilic pneumonia
      (AEP). The patient's respiratory distress resolved within 10 days without
      treatment. Hence, even in an AEP case with atypical radiological presentations,
      careful history taking can lead to a rapid diagnosis.

PMID- 27698010
TI  - Circulating Soluble IL-6R but Not ADAM17 Activation Drives Mononuclear Cell
      Migration in Tissue Inflammation.
AB  - Neutrophil and mononuclear cell infiltration during inflammatory processes is
      highly regulated. The first cells at the site of infection or inflammation are
      neutrophils, followed by mononuclear cells. IL-6 plays an important role during
      inflammatory states. It has been shown in several models that the soluble form of
      IL-6R (sIL-6R) is involved in the recruitment of mononuclear cells by a mechanism
      called IL-6 trans-signaling. It had been speculated that sIL-6R was generated at
      the site of inflammation by shedding from neutrophils via activation of the
      metalloprotease ADAM17. Attempts to genetically delete the floxed ADAM17 gene
      selectively in myeloid cells infiltrating an air pouch cavity upon injection of
      carrageenan failed because in transgenic mice, LysMcre did not lead to
      appreciable loss of the ADAM17 protein in these cells. We therefore used ADAM17
      hypomorphic mice, which only express ~5% of ADAM17 wild-type levels in all
      tissues and show virtually no shedding of all tested ADAM17 substrates, to
      clarify the role of ADAM17 during local inflammation in the murine air pouch
      model. In the present study, we demonstrate that although IL-6 and the trans
      signaling mechanism is mandatory for cellular infiltration in this model, it is
      not ADAM17-mediated shedding of IL-6R within the pouch that orchestrates this
      inflammatory process. Instead, we demonstrate that sIL-6R is infiltrating from
      the circulation in an ADAM17-independent process. Our data suggest that this
      infiltrating sIL-6R, which is needed for IL-6 trans-signaling, is involved in the
      controlled resolution of an acute inflammatory episode.

PMID- 27698011
TI  - Accumulation of CD11c+CD163+ Adipose Tissue Macrophages through Upregulation of
      Intracellular 11beta-HSD1 in Human Obesity.
AB  - Adipose tissue (AT) macrophages (ATMs) are key players for regulation of AT
      homeostasis and obesity-related metabolic disorders. However, the phenotypes of
      human ATMs and regulatory mechanisms of their polarization have not been clearly
      described. In this study, we investigated human ATMs in both abdominal visceral
      AT and s.c. AT and proposed an 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1)-glucocorticoid receptor regulatory axis that might dictate M1/M2
      polarization in ATMs. The accumulation of CD11c+CD163+ ATMs in both visceral AT
      and s.c. AT of obese individuals was confirmed at the cellular level and was
      found to be clearly correlated with body mass index and production of reactive
      oxygen species. Using our in vitro system where human peripheral blood monocytes
      (hPBMs) were cocultured with Simpson-Golabi-Behmel syndrome adipocytes, M1/M2
      polarization was found to be dependent on 11beta-HSD1, an intracellular
      glucocorticoid reactivating enzyme. Exposure of hPBMs to cortisol-induced
      expression of CD163 and RU-486, a glucocorticoid receptor antagonist,
      significantly abrogated CD163 expression through coculture of mature adipocytes
      with hPBMs. Moreover, 11beta-HSD1 was expressed in crown ATMs in obese AT.
      Importantly, conditioned medium from coculture of adipocytes with hPBMs enhanced
      proliferation of human breast cancer MCF7 and MDA-MB-231 cells. In summary, the
      phenotypic switch of ATMs from M2 to mixed M1/M2 phenotype occurred through
      differentiation of adipocytes in obese individuals, and upregulation of
      intracellular 11beta-HSD1 might play a role in the process.

PMID- 27698012
TI  - Von Willebrand Factor Interacts with Surface-Bound C1q and Induces Platelet
      Rolling.
AB  - Premature atherosclerosis and thrombotic complications are major causes of
      morbidity and mortality in patients with systemic lupus erythematosus (SLE).
      However, the high incidence of these complications cannot be explained by
      traditional risk factors alone, suggesting direct effects of an activated immune
      system on hemostasis. The unexpected nucleotide sequence homology between SLE
      patient-derived autoantibodies against complement C1q (Fab anti-C1q) and von
      Willebrand factor (VWF) led us to investigate a potential interaction between the
      complement and hemostatic systems on the level of initiating molecules. VWF was
      found to bind to surface-bound C1q under static conditions. The binding could
      specifically be inhibited by Fab anti-C1q and C1q-derived peptides. Under shear
      stress the C1q-VWF interaction was enhanced, resembling the binding of VWF to
      collagen I. Additionally, we could show that C1q-VWF complexes induced platelet
      rolling and firm adhesion. Furthermore, we observed VWF binding to C1q-positive
      apoptotic microparticles and cholesterol crystals, as well as increased VWF
      deposition in C1q-positive glomeruli of SLE patients compared with control
      nephropathy. We show, to our knowledge for the first time, binding of VWF to C1q
      and thus a direct interaction between starter molecules of hemostasis and the
      classical pathway of complement. This direct interaction might contribute to the
      pathogenic mechanisms in complement-mediated, inflammatory diseases.

PMID- 27698013
TI  - Relationships Between Older Drivers' Cognitive Abilities as Assessed on the MoCA
      and Glance Patterns During Visual-Manual Radio Tuning While Driving.
AB  - Objective: Research has established that long off-road glances increase crash
      risk, and other work has shown increased off-road glance behavior in older
      drivers. This study investigated the relationship between older drivers' (M =
      66.3, range 61-69 years) cognitive abilities and the duration of off-road glances
      while engaged in secondary visual-manual activities. Method: Twenty-two drivers
      completed the Montreal Cognitive Assessment (MoCA) prior to driving an
      instrumented vehicle and completing a set of radio-tuning tasks. Glance behavior
      was recorded and manually coded into 7 glance regions (toward the forward
      roadway, instrument cluster, center stack, rearview mirror, left, right, and
      other). Results: On average, older drivers with higher MoCA scores used shorter
      glances and glanced away from the forward roadway for less total time when
      manually tuning the radio. Discussion: These findings suggest that lower MoCA
      scores may represent a driving force behind the "age" differences reported in
      earlier studies of off-road glance behavior. Questions are raised concerning the
      identification of MoCA scores that might be used as inclusion cut-points in
      driving research and in identifying individuals needing further evaluation
      related to suitability for continuance of driving.

PMID- 27698020
TI  - Interleukin-17 Is Required for Control of Chronic Lung Infection Caused by
      Pseudomonas aeruginosa.
AB  - Chronic pulmonary infection with Pseudomonas aeruginosa is a feature of cystic
      fibrosis (CF) and other chronic lung diseases. Cytokines of the interleukin-17
      (IL-17) family have been proposed as important in the host response to P.
      aeruginosa infection through their role in augmenting antibacterial immune
      responses, although their proinflammatory effect may contribute to lung damage
      that occurs as a result of chronic infection. We set out to explore the role of
      IL-17 in the host response to chronic P. aeruginosa infection. We used a murine
      model of chronic pulmonary infection with CF-related strains of P. aeruginosa We
      demonstrate that IL-17 cytokine signaling is essential for mouse survival and
      prevention of chronic infection at 2 weeks postinoculation using two different P.
      aeruginosa strains. Following infection, there was a marked expansion of cells
      within mediastinal lymph nodes, comprised mainly of innate lymphoid cells (ILCs);
      ~90% of IL-17-producing (IL-17+) cells had markers consistent with group 3 ILCs.
      A smaller percentage of IL-17+ cells had markers consistent with a B1 phenotype.
      In lung homogenates harvested 14 days following infection, there was a
      significant expansion of IL-17+ cells; about 50% of these were CD3+, split
      equally between CD4+ Th17 cells and gammadelta T cells, while the CD3- IL-17+
      cells were almost exclusively group 3 ILCs. Further experiments with B cell
      deficient mice showed that B cell production of IL-17 or natural antibodies did
      not provide any defense against chronic P. aeruginosa infection. Thus, IL-17
      rather than antibody is a key element in host defense against chronic pulmonary
      infection with P. aeruginosa.

PMID- 27698019
TI  - RalF-Mediated Activation of Arf6 Controls Rickettsia typhi Invasion by Co-Opting
      Phosphoinositol Metabolism.
AB  - Rickettsiae are obligate intracellular pathogens that induce their uptake into
      nonphagocytic cells; however, the events instigating this process are
      incompletely understood. Importantly, diverse Rickettsia species are predicted to
      utilize divergent mechanisms to colonize host cells, as nearly all adhesins and
      effectors involved in host cell entry are differentially encoded in diverse
      Rickettsia species. One particular effector, RalF, a Sec7 domain-containing
      protein that functions as a guanine nucleotide exchange factor of ADP
      ribosylation factors (Arfs), is critical for Rickettsia typhi (typhus group
      rickettsiae) entry but pseudogenized or absent from spotted fever group
      rickettsiae. Secreted early during R. typhi infection, RalF localizes to the host
      plasma membrane and interacts with host ADP-ribosylation factor 6 (Arf6). Herein,
      we demonstrate that RalF activates Arf6, a process reliant on a conserved Glu
      within the RalF Sec7 domain. Furthermore, Arf6 is activated early during
      infection, with GTP-bound Arf6 localized to the R. typhi entry foci. The
      regulation of phosphatidylinositol 4-phosphate 5-kinase (PIP5K), which generates
      PI(4,5)P2, by activated Arf6 is instrumental for bacterial entry, corresponding
      to the requirement of PI(4,5)P2 for R. typhi entry. PI(3,4,5)P3 is then
      synthesized at the entry foci, followed by the accumulation of PI(3)P on the
      short-lived vacuole. Inhibition of phosphoinositide 3-kinases, responsible for
      the synthesis of PI(3,4,5)P3 and PI(3)P, negatively affects R. typhi infection.
      Collectively, these results identify RalF as the first bacterial effector to
      directly activate Arf6, a process that initiates alterations in phosphoinositol
      metabolism critical for a lineage-specific Rickettsia entry mechanism.

PMID- 27698021
TI  - Macrophages Promote Oxidative Metabolism To Drive Nitric Oxide Generation in
      Response to Trypanosoma cruzi.
AB  - Trypanosoma cruzi is the causative agent of chronic chagasic cardiomyopathy. Why
      macrophages (mphis), the early responders to infection, fail to achieve parasite
      clearance is not known. Mouse (RAW 264.7) and human (THP-1 and primary) mphis
      were infected for 3 h and 18 h with T. cruzi TcI isolates, SylvioX10/4 (SYL,
      virulent) and TCC (nonpathogenic), which represent mphi stimulation and infection
      states, respectively. Mphis incubated with lipopolysaccharide and gamma
      interferon (LPS/IFN-gamma) and with interleukin-4 (IL-4) were used as controls.
      We monitored the cytokine profile (using enzyme-linked immunosorbent assay
      [ELISA]), reactive oxygen species (ROS; fluorescent probes), nitric oxide (.NO;
      Griess assay), and metabolic state using a custom-designed mitoxosome array and
      Seahorse XF24 Analyzer. LPS/IFN-gamma treatment of mphis elicited a potent
      increase in production of tumor necrosis alpha (TNF-alpha) at 3 h and of ROS and
      .NO by 18 h. Upon SYL infection, murine mphis elicited an inflammatory cytokine
      profile (TNF-alpha ? TGF-beta + IL-10) and low levels of .NO and ROS production.
      LPS/IFN-gamma treatment resulted in the inhibition of oxidative metabolism at the
      gene expression and functional levels and a switch to the glycolytic pathway in
      mphis, while IL-4-treated mphis utilized oxidative metabolism to meet energy
      demands. SYL infection resulted in an intermediate functional metabolic state
      with increased mitoxosome gene expression and glycolysis, and IFN-gamma addition
      shut down the oxidative metabolism in SYL-infected mphis. Further, TCC- and SYL
      stimulated mphis exhibited similar levels of cell proliferation and production of
      TNF-alpha and ROS, while TCC-stimulated mphis exhibited up to 2-fold-higher
      levels of oxidative metabolism and .NO production than SYL-infected mphis.
      Inhibiting ATP-coupled O2 consumption suppressed the .NO generation in SYL
      infected mphis. Mitochondrial oxygen consumption constitutes a mechanism for
      stimulating .NO production in mphis during T. cruzi infection. Enhancing the
      oxidative metabolism provides an opportunity for increased .NO production and
      pathogen clearance by mphis to limit disease progression.

PMID- 27698024
TI  - Effect of HPV on cervical cancer screening in Alberta.

PMID- 27698025
TI  - Functional impairment, not FASD.

PMID- 27698022
TI  - Genetic Determinants of Salmonella enterica Serovar Typhimurium Proliferation in
      the Cytosol of Epithelial Cells.
AB  - Intestinal epithelial cells provide an important colonization niche for
      Salmonella enterica serovar Typhimurium during gastrointestinal infections. In
      infected epithelial cells, a subpopulation of S Typhimurium bacteria damage their
      internalization vacuole, leading to escape from the Salmonella-containing vacuole
      (SCV) and extensive proliferation in the cytosol. Little is known about the
      bacterial determinants of nascent SCV lysis and subsequent survival and
      replication of Salmonella in the cytosol. To pinpoint S Typhimurium virulence
      factors responsible for these steps in the intracellular infectious cycle, we
      screened a S Typhimurium multigene deletion library in Caco-2 C2Bbe1 and HeLa
      epithelial cells for mutants that had an altered proportion of cytosolic bacteria
      compared to the wild type. We used a gentamicin protection assay in combination
      with a chloroquine resistance assay to quantify total and cytosolic bacteria,
      respectively, for each strain. Mutants of three S Typhimurium genes, STM1461
      (ydgT), STM2829 (recA), and STM3952 (corA), had reduced cytosolic proliferation
      compared to wild-type bacteria, and one gene, STM2120 (asmA), displayed increased
      cytosolic replication. None of the mutants were affected for lysis of the nascent
      SCV or vacuolar replication in epithelial cells, indicating that these genes are
      specifically required for survival and proliferation of S Typhimurium in the
      epithelial cell cytosol. These are the first genes identified to contribute to
      this step of the S Typhimurium infectious cycle.

PMID- 27698026
TI  - Incentive payments: the correct lesson.

PMID- 27698027
TI  - Assisted dying for patients with psychiatric disorders.

PMID- 27698028
TI  - A grafted ovarian fragment rescues host fertility after chemotherapy.
AB  - STUDY QUESTION: Can host fertility be rescued by grafting of a fragment of a
      healthy ovary soon after chemotherapy? SUMMARY ANSWER: We found that grafting a
      green fluorescent protein (GFP)-positive fragment from a healthy isogenic ovary
      to the left ovary of a chemo-treated host rescued function and fertility of the
      grafted host ovary, and resulted in the production of host-derived offspring as
      late as the sixth litter after chemotherapy (CTx) treatment, whereas none of the
      ungrafted controls produced a second litter. WHAT IS KNOWN ALREADY: In women and
      girls undergoing chemotherapy, infertility and premature ovarian failure are
      frequent outcomes. There are accumulating reports of improved endocrine function
      after autotransplantation of an ovarian fragment, raising the possibility that
      the transplant is beneficial to the endogenous ovary. STUDY DESIGN, SIZE,
      DURATION: We first established a CTx treatment regimen that resulted in the
      permanent loss of fertility in 100% of female mice of the FVB inbred strain. We
      grafted an isogenic ovary fragment from a healthy female homozygous for a GFP
      transgene to the left ovary of 100 CTx-treated hosts, and compared fertility to
      39 ungrafted controls in 6 months of continuous matings, using GFP to distinguish
      offspring derived from the graft, and those derived from the host.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Immunofluoresece and western blot
      analysis of 39 treated ovaries during and 15 days after CTx treatment revealed
      elevated apoptosis, rapid loss of granulosa cells and an increased recruitment of
      growing follicles. Using immunofluorescence and confocal imaging, we tracked the
      outcome of the grafted tissue over 4 months and its effect on the adjacent and
      contralateral ovary of the host. MAIN RESULTS AND THE ROLE OF CHANCE: Fifty-three
      percent of grafted females produced a second litter whereas none of the ungrafted
      females produced a second litter. The likelihood that this could occur by chance
      is very low (P < 0.0001). LIMITATIONS, REASONS FOR CAUTION: These results are
      shown only in mice, and whether or how they might apply to chemotherapy patients
      subjected to different CTx regimens is not yet clear. WIDER IMPLICATIONS OF THE
      FINDINGS: Our experiments prove that rescue of a chemo-treated ovary is possible,
      and establish a system to investigate the mechanism of rescue and to identify the
      factors responsible with the long-term goal of developing therapies for
      preservation of ovarian endocrine function and fertility in women undergoing
      chemotherapy. LARGE SCALE DATA: No large datasets were produced. STUDY
      FUNDING/COMPETING INTERESTS: Duke University Medical Center Chancellor's
      Discovery Grant to BC; ESJ was supported by an NRSA 5F31CA165545; SK was
      supported by NIH RO1 GM08033; RWT was supported by the Duke University School of
      Medicine Ovarian Cancer Research Fellowship; XBM was supported by CONICYT. The
      authors have no conflicts of interest to declare.

PMID- 27698031
TI  - Chimaera simulation of complex states of flowing matter.
AB  - We discuss a unified mesoscale framework (chimaera) for the simulation of complex
      states of flowing matter across scales of motion. The chimaera framework can deal
      with each of the three macro-meso-micro levels through suitable 'mutations' of
      the basic mesoscale formulation. The idea is illustrated through selected
      simulations of complex micro- and nanoscale flows.This article is part of the
      themed issue 'Multiscale modelling at the physics-chemistry-biology interface'.

PMID- 27698030
TI  - Cytoskeletal Integrators: The Spectrin Superfamily.
AB  - This review discusses the spectrin superfamily of proteins that function to
      connect cytoskeletal elements to each other, the cell membrane, and the nucleus.
      The signature domain is the spectrin repeat, a 106-122-amino-acid segment
      comprising three alpha-helices. alpha-actinin is considered to be the ancestral
      protein and functions to cross-link actin filaments. It then evolved to generate
      spectrin and dystrophin that function to link the actin cytoskeleton to the cell
      membrane, as well as the spectraplakins and plakins that link cytoskeletal
      elements to each other and to junctional complexes. A final class comprises the
      nesprins, which are able to bind to the nuclear membrane. This review discusses
      the domain organization of the various spectrin family members, their roles in
      protein-protein interactions, and their roles in disease, as determined from
      mutations, and it also describes the functional roles of the family members as
      determined from null phenotypes.

PMID- 27698032
TI  - Improved insights into protein thermal stability: from the molecular to the
      structurome scale.
AB  - Despite the intense efforts of the last decades to understand the thermal
      stability of proteins, the mechanisms responsible for its modulation still remain
      debated. In this investigation, we tackle this issue by showing how a multiscale
      perspective can yield new insights. With the help of temperature-dependent
      statistical potentials, we analysed some amino acid interactions at the molecular
      level, which are suggested to be relevant for the enhancement of thermal
      resistance. We then investigated the thermal stability at the protein level by
      quantifying its modification upon amino acid substitutions. Finally, a large
      scale analysis of protein stability-at the structurome level-contributed to the
      clarification of the relation between stability and natural evolution, thereby
      showing that the mutational profile of proteins differs according to their
      thermal properties. Some considerations on how the multiscale approach could help
      in unravelling the protein stability mechanisms are briefly discussed.This
      article is part of the themed issue 'Multiscale modelling at the physics
      chemistry-biology interface'.

PMID- 27698029
TI  - Cell Signaling and Stress Responses.
AB  - Stress-signaling pathways are evolutionarily conserved and play an important role
      in the maintenance of homeostasis. These pathways are also critical for
      adaptation to new cellular environments. The endoplasmic reticulum (ER) unfolded
      protein response (UPR) is activated by biosynthetic stress and leads to a
      compensatory increase in ER function. The JNK and p38 MAPK signaling pathways
      control adaptive responses to intracellular and extracellular stresses, including
      environmental changes such as UV light, heat, and hyperosmotic conditions, and
      exposure to inflammatory cytokines. Metabolic stress caused by a high-fat diet
      represents an example of a stimulus that coordinately activates both the UPR and
      JNK/p38 signaling pathways. Chronic activation of these stress-response pathways
      ultimately causes metabolic changes associated with obesity and altered insulin
      sensitivity. Stress-signaling pathways, therefore, represent potential targets
      for therapeutic intervention in the metabolic stress response and other disease
      processes.

PMID- 27698033
TI  - Probing the mechanisms for the selectivity and promiscuity of methyl parathion
      hydrolase.
AB  - Diverse organophosphate hydrolases have convergently evolved the ability to
      hydrolyse man-made organophosphates. Thus, these enzymes are attractive model
      systems for studying the factors shaping enzyme functional evolution. Methyl
      parathion hydrolase (MPH) is an enzyme from the metallo-beta-lactamase
      superfamily, which hydrolyses a wide range of organophosphate, aryl ester and
      lactone substrates. In addition, MPH demonstrates metal-ion-dependent selectivity
      patterns. The origins of this remain unclear, but are linked to open questions
      about the more general role of metal ions in functional evolution and divergence
      within enzyme superfamilies. Here, we present detailed mechanistic studies of the
      paraoxonase and arylesterase activities of MPH complexed with five different
      transition metal ions, and demonstrate that the hydrolysis reactions proceed via
      similar pathways and transition states. However, while it is possible to discern
      a clear structural origin for the selectivity between different substrates, the
      selectivity between different metal ions appears to lie instead in the distinct
      electrostatic properties of the metal ions themselves, which causes subtle
      changes in transition state geometries and metal-metal distances at the
      transition state rather than significant structural changes in the active site.
      While subtle, these differences can be significant for shaping the metal-ion
      dependent activity patterns observed for this enzyme.This article is part of the
      themed issue 'Multiscale modelling at the physics-chemistry-biology interface'.

PMID- 27698034
TI  - Kinetics of intercalation of fluorescent probes in magnesium-aluminium layered
      double hydroxide within a multiscale reaction-diffusion framework.
AB  - We report the synthesis of magnesium-aluminium layered double hydroxide (LDH)
      using a reaction-diffusion framework (RDF) that exploits the multiscale coupling
      of molecular diffusion with chemical reactions, nucleation and growth of
      crystals. In an RDF, the hydroxide anions are allowed to diffuse into an organic
      gel matrix containing the salt mixture needed for the precipitation of the LDH.
      The chemical structure and composition of the synthesized magnesium-aluminium
      LDHs are determined using powder X-ray diffraction (PXRD), thermo-gravimetric
      analysis, differential scanning calorimetry, solid-state nuclear magnetic
      resonance (SSNMR), Fourier transform infrared and energy dispersive X-ray
      spectroscopy. This novel technique also allows the investigation of the mechanism
      of intercalation of some fluorescent probes, such as the neutral three
      dimensional rhodamine B (RhB) and the negatively charged two-dimensional 8
      hydroxypyrene-1,3,6-trisulfonic acid (HPTS), using in situ steady-state
      fluorescence spectroscopy. The incorporation of these organic dyes inside the
      interlayer region of the LDH is confirmed via fluorescence microscopy, solid
      state lifetime, SSNMR and PXRD. The activation energies of intercalation of the
      corresponding molecules (RhB and HPTS) are computed and exhibit dependence on the
      geometry of the involved probe (two or three dimensions), the charge of the
      fluorescent molecule (anionic, cationic or neutral) and the cationic ratio of the
      corresponding LDH.This article is part of the themed issue 'Multiscale modelling
      at the physics-chemistry-biology interface'.

PMID- 27698035
TI  - Big data need big theory too.
AB  - The current interest in big data, machine learning and data analytics has
      generated the widespread impression that such methods are capable of solving most
      problems without the need for conventional scientific methods of inquiry.
      Interest in these methods is intensifying, accelerated by the ease with which
      digitized data can be acquired in virtually all fields of endeavour, from
      science, healthcare and cybersecurity to economics, social sciences and the
      humanities. In multiscale modelling, machine learning appears to provide a
      shortcut to reveal correlations of arbitrary complexity between processes at the
      atomic, molecular, meso- and macroscales. Here, we point out the weaknesses of
      pure big data approaches with particular focus on biology and medicine, which
      fail to provide conceptual accounts for the processes to which they are applied.
      No matter their 'depth' and the sophistication of data-driven methods, such as
      artificial neural nets, in the end they merely fit curves to existing data. Not
      only do these methods invariably require far larger quantities of data than
      anticipated by big data aficionados in order to produce statistically reliable
      results, but they can also fail in circumstances beyond the range of the data
      used to train them because they are not designed to model the structural
      characteristics of the underlying system. We argue that it is vital to use theory
      as a guide to experimental design for maximal efficiency of data collection and
      to produce reliable predictive models and conceptual knowledge. Rather than
      continuing to fund, pursue and promote 'blind' big data projects with massive
      budgets, we call for more funding to be allocated to the elucidation of the
      multiscale and stochastic processes controlling the behaviour of complex systems,
      including those of life, medicine and healthcare.This article is part of the
      themed issue 'Multiscale modelling at the physics-chemistry-biology interface'.

PMID- 27698036
TI  - Towards the virtual artery: a multiscale model for vascular physiology at the
      physics-chemistry-biology interface.
AB  - This discussion paper introduces the concept of the Virtual Artery as a
      multiscale model for arterial physiology and pathologies at the physics-chemistry
      biology (PCB) interface. The cellular level is identified as the mesoscopic
      level, and we argue that by coupling cell-based models with other relevant models
      on the macro- and microscale, a versatile model of arterial health and disease
      can be composed. We review the necessary ingredients, both models of arteries at
      many different scales, as well as generic methods to compose multiscale models.
      Next, we discuss how this can be combined into the virtual artery. Finally, we
      argue that the concept of models at the PCB interface could or perhaps should
      become a powerful paradigm, not only as in our case for studying physiology, but
      also for many other systems that have such PCB interfaces.This article is part of
      the themed issue 'Multiscale modelling at the physics-chemistry-biology
      interface'.

PMID- 27698037
TI  - Microscopic and continuum descriptions of Janus motor fluid flow fields.
AB  - Active media, whose constituents are able to move autonomously, display novel
      features that differ from those of equilibrium systems. In addition to naturally
      occurring active systems such as populations of swimming bacteria, active systems
      of synthetic self-propelled nanomotors have been developed. These synthetic
      systems are interesting because of their potential applications in a variety of
      fields. Janus particles, synthetic motors of spherical geometry with one
      hemisphere that catalyses the conversion of fuel to product and one non-catalytic
      hemisphere, can propel themselves in solution by self-diffusiophoresis. In this
      mechanism, the concentration gradient generated by the asymmetric catalytic
      activity leads to a force on the motor that induces fluid flows in the
      surrounding medium. These fluid flows are studied in detail through microscopic
      simulations of Janus motor motion and continuum theory. It is shown that
      continuum theory is able to capture many, but not all, features of the dynamics
      of the Janus motor and the velocity fields of the fluid.This article is part of
      the themed issue 'Multiscale modelling at the physics-chemistry-biology
      interface'.

PMID- 27698039
TI  - Invariance principle and model reduction for the Fokker-Planck equation.
AB  - The principle of dynamic invariance is applied to obtain closed moment equations
      from the Fokker-Planck kinetic equation. The analysis is carried out to explicit
      formulae for computation of the lowest eigenvalue and of the corresponding
      eigenfunction for arbitrary potentials.This article is part of the themed issue
      'Multiscale modelling at the physics-chemistry-biology interface'.

PMID- 27698040
TI  - Generation of mechanical force by grafted polyelectrolytes in an electric field:
      application to polyelectrolyte-based nano-devices.
AB  - We analyse theoretically and by means of molecular dynamics (MD) simulations the
      generation of mechanical force by a polyelectrolyte (PE) chain grafted to a
      plane. The PE is exposed to an external electric field that favours its
      adsorption on the plane. The free end of the chain is linked to a deformable
      target body. By varying the field, one can alter the length of the non-adsorbed
      part of the chain. This entails variation of the deformation of the target body
      and hence variation of the force arising in the body. Our theoretical predictions
      for the generated force are in very good agreement with the MD data. Using the
      theory developed for the generated force, we study the effectiveness of possible
      PE-based nano-vices, composed of two clenching planes connected by PEs and
      exposed to an external electric field. We exploit the Cundall-Strack solid
      friction model to describe the friction between a particle and the clenching
      planes. We compute the diffusion coefficient of a clenched particle and show that
      it drastically decreases even in weak applied fields. This demonstrates the
      efficacy of the PE-based nano-vices, which may be a possible alternative to the
      existing nanotube nano-tweezers and optical tweezers.This article is part of the
      themed issue 'Multiscale modelling at the physics-chemistry-biology interface'.

PMID- 27698038
TI  - A perspective on bridging scales and design of models using low-dimensional
      manifolds and data-driven model inference.
AB  - Systems in nature capable of collective behaviour are nonlinear, operating across
      several scales. Yet our ability to account for their collective dynamics differs
      in physics, chemistry and biology. Here, we briefly review the similarities and
      differences between mathematical modelling of adaptive living systems versus
      physico-chemical systems. We find that physics-based chemistry modelling and
      computational neuroscience have a shared interest in developing techniques for
      model reductions aiming at the identification of a reduced subsystem or slow
      manifold, capturing the effective dynamics. By contrast, as relations and
      kinetics between biological molecules are less characterized, current
      quantitative analysis under the umbrella of bioinformatics focuses on signal
      extraction, correlation, regression and machine-learning analysis. We argue that
      model reduction analysis and the ensuing identification of manifolds bridges
      physics and biology. Furthermore, modelling living systems presents deep
      challenges as how to reconcile rich molecular data with inherent modelling
      uncertainties (formalism, variables selection and model parameters). We
      anticipate a new generative data-driven modelling paradigm constrained by
      identified governing principles extracted from low-dimensional manifold analysis.
      The rise of a new generation of models will ultimately connect biology to
      quantitative mechanistic descriptions, thereby setting the stage for
      investigating the character of the model language and principles driving living
      systems.This article is part of the themed issue 'Multiscale modelling at the
      physics-chemistry-biology interface'.

PMID- 27698041
TI  - Evaluating dispersion forces for optimization of van der Waals complexes using a
      non-empirical functional.
AB  - Modelling dispersion interactions with traditional density functional theory
      (DFT) is a challenge that has been extensively addressed in the past decade. The
      exchange-dipole moment (XDM), among others, is a non-empirical add-on dispersion
      correction model in DFT. The functional PW86+PBE+XDM for exchange, correlation
      and dispersion, respectively, compromises an accurate functional for
      thermochemistry and for van der Waals (vdW) complexes at equilibrium and non
      equilibrium geometries. To use this functional in optimizing vdW complexes,
      rather than computing single point energies, it is necessary to evaluate accurate
      forces. The purpose of this paper is to validate that, along the potential energy
      surface, the distance at which the energy is minimum is commensurate with the
      distance at which the forces vanish to zero. This test was validated for 10 rare
      gas diatomic molecules using various integration grids and different convergence
      criteria. It was found that the use of either convergence criterion, 10-6 or 10
      8, in Gaussian09, does not affect the accuracy of computed optimal distances and
      binding energies. An ultra-fine grid needs to be used when computing accurate
      energies using generalized gradient approximation functionals.This article is
      part of the themed issue 'Multiscale modelling at the physics-chemistry-biology
      interface'.

PMID- 27698042
TI  - Reaction-diffusion basis of retroviral infectivity.
AB  - Retrovirus particle (virion) infectivity requires diffusion and clustering of
      multiple transmembrane envelope proteins (Env3) on the virion exterior, yet is
      triggered by protease-dependent degradation of a partially occluding, membrane
      bound Gag polyprotein lattice on the virion interior. The physical mechanism
      underlying such coupling is unclear and only indirectly accessible via
      experiment. Modelling stands to provide insight but the required spatio-temporal
      range far exceeds current accessibility by all-atom or even coarse-grained
      molecular dynamics simulations. Nor do such approaches account for chemical
      reactions, while conversely, reaction kinetics approaches handle neither
      diffusion nor clustering. Here, a recently developed multiscale approach is
      considered that applies an ultra-coarse-graining scheme to treat entire proteins
      at near-single particle resolution, but which also couples chemical reactions
      with diffusion and interactions. A model is developed of Env3 molecules embedded
      in a truncated Gag lattice composed of membrane-bound matrix proteins linked to
      capsid subunits, with freely diffusing protease molecules. Simulations suggest
      that in the presence of Gag but in the absence of lateral lattice-forming
      interactions, Env3 diffuses comparably to Gag-absent Env3 Initial immobility of
      Env3 is conferred through lateral caging by matrix trimers vertically coupled to
      the underlying hexameric capsid layer. Gag cleavage by protease vertically
      decouples the matrix and capsid layers, induces both matrix and Env3 diffusion,
      and permits Env3 clustering. Spreading across the entire membrane surface reduces
      crowding, in turn, enhancing the effect and promoting infectivity.This article is
      part of the themed issue 'Multiscale modelling at the physics-chemistry-biology
      interface'.

PMID- 27698043
TI  - Kinetics and thermodynamics of living copolymerization processes.
AB  - Theoretical advances are reported on the kinetics and thermodynamics of free and
      template-directed living copolymerizations. Until recently, the kinetic theory of
      these processes had only been established in the fully irreversible regime, in
      which the attachment rates are only considered. However, the entropy production
      is infinite in this regime and the approach to thermodynamic equilibrium cannot
      be investigated. For this purpose, the detachment rates should also be included.
      Inspite of this complication, the kinetics can be exactly solved in the regimes
      of steady growth and depolymerization. In this way, analytical expressions are
      obtained for the mean growth velocity, the statistical properties of the
      copolymer sequences, as well as the thermodynamic entropy production. The results
      apply to DNA replication, transcription and translation, allowing us to
      understand important aspects of molecular evolution.This article is part of the
      themed issue 'Multiscale modelling at the physics-chemistry-biology interface'.

PMID- 27698044
TI  - Thermodynamics of adaptive molecular resolution.
AB  - A relatively general thermodynamic formalism for adaptive molecular resolution
      (AMR) is presented. The description is based on the approximation of local
      thermodynamic equilibrium and considers the alchemic parameter lambda as the
      conjugate variable of the potential energy difference between the atomistic and
      coarse-grained model Phi=U(1)-U(0) The thermodynamic formalism recovers the
      relations obtained from statistical mechanics of H-AdResS (Espanol et al, J.
      Chem. Phys. 142, 064115, 2015 (doi:10.1063/1.4907006)) and provides relations
      between the free energy compensation and thermodynamic potentials. Inspired by
      this thermodynamic analogy, several generalizations of AMR are proposed, such as
      the exploration of new Maxwell relations and how to treat lambda and Phi as
      'real' thermodynamic variablesThis article is part of the themed issue
      'Multiscale modelling at the physics-chemistry-biology interface'.

PMID- 27698045
TI  - Lattice Boltzmann accelerated direct simulation Monte Carlo for dilute gas flow
      simulations.
AB  - Hybrid particle-continuum computational frameworks permit the simulation of gas
      flows by locally adjusting the resolution to the degree of non-equilibrium
      displayed by the flow in different regions of space and time. In this work, we
      present a new scheme that couples the direct simulation Monte Carlo (DSMC) with
      the lattice Boltzmann (LB) method in the limit of isothermal flows. The former
      handles strong non-equilibrium effects, as they typically occur in the vicinity
      of solid boundaries, whereas the latter is in charge of the bulk flow, where non
      equilibrium can be dealt with perturbatively, i.e. according to Navier-Stokes
      hydrodynamics. The proposed concurrent multiscale method is applied to the dilute
      gas Couette flow, showing major computational gains when compared with the full
      DSMC scenarios. In addition, it is shown that the coupling with LB in the bulk
      flow can speed up the DSMC treatment of the Knudsen layer with respect to the
      full DSMC case. In other words, LB acts as a DSMC accelerator.This article is
      part of the themed issue 'Multiscale modelling at the physics-chemistry-biology
      interface'.

PMID- 27698046
TI  - Multiscale simulation of molecular processes in cellular environments.
AB  - We describe the recent advances in studying biological systems via multiscale
      simulations. Our scheme is based on a coarse-grained representation of the
      macromolecules and a mesoscopic description of the solvent. The dual technique
      handles particles, the aqueous solvent and their mutual exchange of forces
      resulting in a stable and accurate methodology allowing biosystems of
      unprecedented size to be simulated.This article is part of the themed issue
      'Multiscale modelling at the physics-chemistry-biology interface'.

PMID- 27698047
TI  - Bridging the gaps at the physics-chemistry-biology interface.

PMID- 27698048
TI  - Immature Platelets: Clinical Relevance and Research Perspectives.

PMID- 27698049
TI  - Returning to Work: A Forgotten Aspect of Rehabilitation for Heart Failure.

PMID- 27698050
TI  - Energy Drinks Pose Worrisome Risks to Adolescents' Cardiovascular Health.

PMID- 27698051
TI  - Not Just Another Notch.

PMID- 27698052
TI  - Letter by Kataoka et al Regarding Article, "Dynamic Risk Stratification of
      Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United
      Kingdom National Cohort".

PMID- 27698053
TI  - Response by Cannon and Pepke-Zaba to Letter Regarding Article, "Dynamic Risk
      Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy:
      Results From the United Kingdom National Cohort".

PMID- 27698054
TI  - Letter by Antignac et al Regarding Article "Access to Medications for
      Cardiovascular Diseases in Low- and Middle-Income Countries".

PMID- 27698055
TI  - Response by Wirtz et al to Letter Regarding Article, "Access to Medications for
      Cardiovascular Diseases in Low- and Middle-Income Countries".

PMID- 27698056
TI  - Correction to: Heart Failure With Preserved Ejection Fraction: A Kidney Disorder?

PMID- 27698058
TI  - How Does Angiotensin Activate Hypothalamic Neurons Essential for Controlling
      Sympathetic Activity and Blood Pressure?

PMID- 27698060
TI  - Sympathetic Activity, Hypertension, and The Importance of a Good Night's Sleep.

PMID- 27698059
TI  - Gaps in Hypertension Guidelines in Low- and Middle-Income Versus High-Income
      Countries: A Systematic Review.

PMID- 27698061
TI  - Mnk1 (Mitogen-Activated Protein Kinase-Interacting Kinase 1) Deficiency
      Aggravates Cardiac Remodeling in Mice.
AB  - Identifying the key factor involved in cardiac remodeling is critically important
      for developing novel strategies to protect against heart failure. Here, the role
      of Mnk1 (mitogen-activated protein kinase-interacting kinase 1) in cardiac
      remodeling was clarified. Cardiac remodeling was induced by transverse aortic
      constriction in Mnk1-knockout mice and their wild-type control mice. After 4
      weeks of transverse aortic constriction, Mnk1-knockout mice developed exaggerated
      cardiac hypertrophy, fibrosis, dysfunction, and cardiomyocyte apoptosis and
      showed increased ERK1/2 (extracellular signal-regulated kinase 1/2) activation
      along with reduced sprouty2 expression. In line with the in vivo studies, Mnk1
      knockdown by Mnk1 siRNA transfection induced exaggerated angiotensin II-induced
      cardiomyocyte hypertrophy in neonatal rat ventricular myocytes (NRVMs). Moreover,
      adenovirus-mediated overexpression of Mnk1 in NRVMs protected cardiomyocytes from
      angiotensin II-induced hypertrophy. In addition, overexpression of sprouty2
      rescued NRVMs with Mnk1 knockdown from angiotensin II-induced hypertrophy. In
      accordance with the in vivo studies, as compared with the control group, Mnk1
      knockdown led to hyperphosphorylation of ERK1/2 and suppression of the sprouty2
      expression in angiotensin II-treated NRVMs; furthermore, Mnk1 overexpression led
      to hypophosphorylation of ERK1/2 in angiotensin II-treated NRVMs. In addition,
      sprouty2 overexpression suppressed the activation of ERK1/2 in angiotensin II
      treated NRVMs with Mnk1 knockdown. Impressively, MnK1-knockout mice with
      overexpression of sprouty2 exhibited signs of a blunted cardiac hypertrophic
      response. Mnk1 likely carries out a suppressive function in cardiac hypertrophy
      via regulating the sprouty2/ERK1/2 pathway. It implicates Mnk1 in the development
      of cardiac remodeling.

PMID- 27698062
TI  - Agonistic Autoantibodies to the Angiotensin II Type 1 Receptor Enhance
      Angiotensin II-Induced Renal Vascular Sensitivity and Reduce Renal Function
      During Pregnancy.
AB  - Preeclamptic women produce agonistic autoantibodies to the angiotensin II type 1
      receptor (AT1-AA) and exhibit increased blood pressure (mean arterial pressure),
      vascular sensitivity to angiotensin II (ANG II), and display a decrease in renal
      function. The objective of this study was to examine the renal hemodynamic
      changes during pregnancy in the presence of AT1-AAs with or without a slow
      pressor dose of ANG II. In this study, mean arterial pressure was elevated in all
      pregnant rats treated with ANG II with or without AT1-AA. Glomerular filtration
      rate was reduced from 1.90+/-0.16 mL/min in normal pregnant (NP) to 1.20+/-0.08
      in ANG II+AT1-AA rats. Renal blood flow was decreased in ANG II+AT1-AA versus NP
      rats to 7.4+/-1.09 versus 15.4+/-1.75 mL/min. Renal vascular resistance was
      drastically increased between ANG II+AT1-AA versus NP rats (18.4+/-2.91 versus
      6.4+/-0.77 mm Hg/mL per minute). Isoprostane excretion was increased by 3.5-fold
      in ANG II+AT1-AA versus NP (1160+/-321 versus 323+/-52 pg/mL). In conclusion, ANG
      II and AT1-AA together significantly decrease glomerular filtration rate by 37%
      and renal blood flow by 50% and caused a 3-fold increase in renal vascular
      resistance and isoprostane levels versus NP rats. These data indicate the
      importance of AT1-AAs to enhance ANG II-induced renal vasoconstriction and reduce
      renal function as mechanisms to cause hypertension as observed during
      preeclampsia.

PMID- 27698063
TI  - Extent of Vascular Remodeling Is Dependent on the Balance Between Estrogen
      Receptor alpha and G-Protein-Coupled Estrogen Receptor.
AB  - Estrogens are important regulators of cardiovascular function. Some of estrogen's
      cardiovascular effects are mediated by a G-protein-coupled receptor mechanism,
      namely, G-protein-coupled estrogen receptor (GPER). Estradiol-mediated regulation
      of vascular cell programmed cell death reflects the balance of the opposing
      actions of GPER versus estrogen receptor alpha (ERalpha). However, the
      significance of these opposing actions on the regulation of vascular smooth
      muscle cell proliferation or migration in vitro is unclear, and the significance
      in vivo is unknown. To determine the effects of GPER activation in vitro, we
      studied rat aortic vascular smooth muscle cells maintained in primary culture.
      GPER was reintroduced using adenoviral gene transfer. Both estradiol and G1, a
      GPER agonist, inhibited both proliferation and cell migration effects that were
      blocked by the GPER antagonist, G15. To determine the importance of the GPER
      ERalpha balance in regulating vascular remodeling in a rat model of carotid
      ligation, we studied the effects of upregulation of GPER expression versus
      downregulation of ERalpha. Reintroduction of GPER significantly attenuated the
      extent of medial hypertrophy and attenuated the extent of CD45 labeling.
      Downregulation of ERalpha expression comparably attenuated the extent of medial
      hypertrophy and inflammation after carotid ligation. These studies demonstrate
      that the balance between GPER and ERalpha regulates vascular remodeling. Receptor
      specific modulation of estrogen's effects may be an important new approach in
      modifying vascular remodeling in both acute settings like vascular injury and
      perhaps in longer term regulation like in hypertension.

PMID- 27698064
TI  - A Novel Mechanism of Action for Angiotensin-(1-7) via the Angiotensin Type 1
      Receptor.

PMID- 27698065
TI  - Fluid Shear Stress Promotes Placental Growth Factor Upregulation in Human
      Syncytiotrophoblast Through the cAMP-PKA Signaling Pathway.
AB  - The effects of fluid shear stress (FSS) on the human syncytiotrophoblast and its
      biological functions have never been studied. During pregnancy, the
      syncytiotrophoblast is the main source of placental growth factor (PlGF), a
      proangiogenic factor involved in the placental angiogenesis and the vascular
      adaptation to pregnancy. The role of FSS in regulating PlGF expression in
      syncytiotrophoblasts is unknown. We investigated the impact of FSS on the
      production and secretion of the PlGF by the human syncytiotrophoblasts in primary
      cell culture. Laminar and continuous FSS (1 dyn cm-2) was applied to human
      syncytiotrophoblasts cultured in a parallel-plate flow chambers. Secreted levels
      of PlGF, sFlt-1 (soluble fms-like tyrosin kinase-1), and prostaglandin E2 were
      tested by immunologic assay. PlGF levels of mRNA and intracellular protein were
      examined by RT-PCR and Western blot, respectively. Intracellular cAMP levels were
      examined by time-resolved fluorescence resonance energy transfer cAMP
      accumulation assay. Production of cAMP and PlGF secretion was significantly
      increased in FSS conditions compared with static conditions. Western blot
      analysis of cell extracts exposed to FSS showed an increased phosphorylation of
      protein kinase A substrates and cAMP response element-binding protein on serine
      133. FSS-induced phosphorylation of cAMP response element-binding protein and
      upregulation of PlGF were prevented by inhibition of protein kinase A with H89 (3
      MUmol/L). FSS also triggers intracellular calcium flux, which increases the
      synthesis and release of prostaglandin E2. The enhanced intracellular cAMP in FSS
      conditions was blocked by COX1/COX2 (cyclooxygenase) inhibitors, suggesting that
      the increase in prostaglandin E2 production could activate the cAMP/protein
      kinase A pathway in an autocrine/paracrine fashion. FSS activates the
      cAMP/protein kinase A pathway leading to upregulation of PlGF in human
      syncytiotrophoblast.

PMID- 27698066
TI  - Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the
      Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt
      Hypertension.
AB  - Renal sympathetic denervation (RDNx) has emerged as a novel therapy for
      hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal
      sympathetic nerve activity has recently been implicated in trafficking renal
      inflammatory immune cells and inflammatory chemokine and cytokine release.
      Several of these inflammatory mediators are known to activate or sensitize
      afferent nerves. This study aimed to elucidate the roles of efferent and afferent
      renal nerves in renal inflammation and hypertension in the deoxycorticosterone
      acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275
      300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham
      (n=10) and were instrumented for the measurement of mean arterial pressure and
      heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for
      21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was
      measured after the treatment protocol. Renal tissue inflammation was assessed by
      renal cytokine content and T-cell infiltration and activation. Resting afferent
      renal nerve activity, expressed as a percent of peak afferent nerve activity, was
      substantially increased in DOCA than in vehicle (35.8+/-4.4 versus 15.3+/-2.8
      %Amax). The DOCA-Sham hypertension (132+/-12 mm Hg) was attenuated by ~50% in
      both total RDNx (111+/-8 mm Hg) and afferent-selective RDNx (117+/-5 mm Hg)
      groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and
      unaffected by afferent-selective RDNx. These data suggest that afferent renal
      nerve activity may mediate the hypertensive response to DOCA salt, but
      inflammation may be mediated primarily by efferent renal sympathetic nerve
      activity. Also, resting afferent renal nerve activity is elevated in DOCA salt
      rats, which may highlight a crucial neural mechanism in the development and
      maintenance of hypertension.

PMID- 27698067
TI  - Cardiac Consequences of Autonomic Dysreflexia in Spinal Cord Injury.
AB  - Autonomic dysreflexia (AD), which describes episodic hypertension, is highly
      prevalent in people with spinal cord injury (SCI). In non-SCI, primary
      hypertension depresses cardiac contractile reserve via beta-adrenergic
      mechanisms. In this study, we investigated whether AD contributes to the
      impairment in cardiac contractile function that accompanies SCI. We induced SCI
      in rodents and stratified them into sham, SCI, or SCI plus repetitive induction
      of AD. At 6-week post-SCI, we assessed cardiac function using in vivo (speckle
      tracking echocardiography), ex vivo (working heart), and molecular approaches
      (Western blot). We also provide unique translational insight by comparing the
      relationship between the number of daily AD events and cardiac function in 14
      individuals with cervical SCI. We found SCI and SCI plus repetitive induction of
      AD exhibited a reduction in left ventricular dimensions at 6-week post-SCI versus
      preinjury (P<0.049). Compared with sham, SCI exhibited a reduction in peak radial
      strain along with a down and rightward shift in the Starling curve (P<0.037),
      both of which were further depressed in SCI plus repetitive induction of AD
      (P<0.042). In response to beta-adrenergic stimulation, SCI plus repetitive
      induction of AD exhibited an attenuated increase in contractile indices
      (P<0.001), despite no differences in beta-receptor expression within the left
      ventricle. Our clinical data confirm our experimental findings by demonstrating
      significant associations between the number of daily AD events and markers of
      systolic and diastolic function along with left ventricular mechanics. Here, we
      provide the first evidence from a translational perspective that AD exerts
      insidious effects on cardiac function in rodents and humans with SCI.

PMID- 27698068
TI  - Cardioprotective Angiotensin-(1-7) Peptide Acts as a Natural-Biased Ligand at the
      Angiotensin II Type 1 Receptor.
AB  - Hyperactivity of the renin-angiotensin-aldosterone system through the angiotensin
      II (Ang II)/Ang II type 1 receptor (AT1-R) axis constitutes a hallmark of
      hypertension. Recent findings indicate that only a subset of AT1-R signaling
      pathways is cardiodeleterious, and their selective inhibition by biased ligands
      promotes therapeutic benefit. To date, only synthetic biased ligands have been
      described, and whether natural renin-angiotensin-aldosterone system peptides
      exhibit functional selectivity at AT1-R remains unknown. In this study, we
      systematically determined efficacy and potency of Ang II, Ang III, Ang IV, and
      Ang-(1-7) in AT1-R-expressing HEK293T cells on the activation of
      cardiodeleterious G-proteins and cardioprotective beta-arrestin2. Ang III and Ang
      IV fully activate similar G-proteins than Ang II, the prototypical AT1-R agonist,
      despite weaker potency of Ang IV. Interestingly, Ang-(1-7) that binds AT1-R fails
      to promote G-protein activation but behaves as a competitive antagonist for Ang
      II/Gi and Ang II/Gq pathways. Conversely, all renin-angiotensin-aldosterone
      system peptides act as agonists on the AT1-R/beta-arrestin2 axis but display
      biased activities relative to Ang II as indicated by their differences in potency
      and AT1-R/beta-arrestin2 intracellular routing. Importantly, we reveal Ang-(1-7)
      a known Mas receptor-specific ligand, as an AT1-R-biased agonist, selectively
      promoting beta-arrestin activation while blocking the detrimental Ang II/AT1-R/Gq
      axis. This original pharmacological profile of Ang-(1-7) at AT1-R, similar to
      that of synthetic AT1-R-biased agonists, could, in part, contribute to its
      cardiovascular benefits. Accordingly, in vivo, Ang-(1-7) counteracts the
      phenylephrine-induced aorta contraction, which was blunted in AT1-R knockout
      mice. Collectively, these data suggest that Ang-(1-7) natural-biased agonism at
      AT1-R could fine-tune the physiology of the renin-angiotensin-aldosterone system.

PMID- 27698069
TI  - Astrocytes Contribute to Angiotensin II Stimulation of Hypothalamic Neuronal
      Activity and Sympathetic Outflow.
AB  - Angiotensin II (AngII) is a key neuropeptide that acting within the brain
      hypothalamic paraventricular nucleus regulates neurohumoral outflow to the
      circulation. Moreover, an exacerbated AngII action within the paraventricular
      nucleus contributes to neurohumoral activation in hypertension. Although AngII
      effects involve changes in paraventricular nucleus neuronal activity, the precise
      underlying mechanisms, cellular targets, and distribution of AngII receptors
      within the paraventricular nucleus remain largely unknown. Thus, whether AngII
      effects involve direct actions on paraventricular neurons, or whether it acts via
      intermediary cells, such as astrocytes, is still controversial. To address this
      important gap in our knowledge, we used a multidisciplinary approach combining
      patch-clamp electrophysiology in presympathetic paraventricular neurons and
      astrocytes, along with in vivo sympathetic nerve recordings and astrocyte
      targeted gene manipulations. We present evidence for a novel mechanism underlying
      central AngII actions, which involves astrocytes as major intermediary cellular
      targets. We found that AngII type 1 receptor mRNA is expressed in paraventricular
      astrocytes. Moreover, we report that AngII inhibited glutamate transporter
      function, increasing in turn extracellular glutamate levels. This resulted in the
      activation of neuronal extrasynaptic NMDA (N-methyl-d-aspartate) receptors,
      increased presympathetic neuronal activity, enhanced sympathoexcitatory outflow,
      and increased blood pressure. Together, our studies support astrocytes as
      critical intermediary cell types mediating brain AngII regulation of the
      circulation and indicate that AngII-mediated neuronal and sympathoexcitatory
      effects are dependent on a unique neuroglial signaling modality involving
      nonsynaptic glutamate transmission.

PMID- 27698070
TI  - Arousal From Sleep and Sympathetic Excitation During Wakefulness.
AB  - Obstructive apnea during sleep elevates the set point for efferent sympathetic
      outflow during wakefulness. Such resetting is attributed to hypoxia-induced
      upregulation of peripheral chemoreceptor and brain stem sympathetic function.
      Whether recurrent arousal from sleep also influences daytime muscle sympathetic
      nerve activity is unknown. We therefore tested, in a cohort of 48 primarily
      nonsleepy, middle-aged, male (30) and female (18) volunteers (age: 59+/-1 years,
      mean+/-SE), the hypothesis that the frequency of arousals from sleep (arousal
      index) would relate to daytime muscle sympathetic burst incidence, independently
      of the frequency of apnea or its severity. Polysomnography identified 24 as
      having either no or mild obstructive sleep apnea (apnea-hypopnea index <15
      events/h) and 24 with moderate-to-severe obstructive sleep apnea (apnea-hypopnea
      index >15 events/h). Burst incidence correlated significantly with arousal index
      (r=0.53; P<0.001), minimum oxygen saturation (r=-0.43; P=0.002), apnea-hypopnea
      index (r=0.41; P=0.004), age (r=0.36; P=0.013), and body mass index (r=0.33;
      P=0.022) but not with oxygen desaturation index (r=0.28; P=0.056). Arousal index
      was the single strongest predictor of muscle sympathetic nerve activity burst
      incidence, present in all best subsets regression models. The model with the
      highest adjusted R2 (0.456) incorporated arousal index, minimum oxygen
      saturation, age, body mass index, and oxygen desaturation index but not apnea
      hypopnea index. An apnea- and hypoxia-independent effect of sleep fragmentation
      on sympathetic discharge during wakefulness could contribute to intersubject
      variability, age-related increases in muscle sympathetic nerve activity,
      associations between sleep deprivation and insulin resistance or insomnia and
      future cardiovascular events, and residual adrenergic risk with persistence of
      hypertension should therapy eliminate obstructive apneas but not arousals.

PMID- 27698071
TI  - Nonmutational compensation of the fitness cost of antibiotic resistance in
      mycobacteria by overexpression of tlyA rRNA methylase.
AB  - Several studies over the last few decades have shown that antibiotic resistance
      mechanisms frequently confer a fitness cost and that these costs can be
      genetically ameliorated by intra- or extragenic second-site mutations, often
      without loss of resistance. Another, much less studied potential mechanism by
      which the fitness cost of antibiotic resistance could be reduced is via a
      regulatory response where the deleterious effect of the resistance mechanism is
      lowered by a physiological alteration that buffers the mutational effect. In
      mycobacteria, resistance to the clinically used tuberactinomycin antibiotic
      capreomycin involves loss-of-function mutations in rRNA methylase TlyA or point
      mutations in 16S rRNA (in particular the A1408G mutation). Both of these
      alterations result in resistance by reducing drug binding to the ribosome. Here
      we show that alterations of tlyA gene expression affect both antibiotic drug
      susceptibility and fitness cost of drug resistance. In particular, we demonstrate
      that the common resistance mutation A1408G is accompanied by a physiological
      change that involves increased expression of the tlyA gene. This gene encodes an
      enzyme that methylates neighboring 16S rRNA position C1409, and as a result of
      increased TlyA expression the fitness cost of the A1408G mutation is
      significantly reduced. Our findings suggest that in mycobacteria, a nonmutational
      mechanism (i.e., gene regulatory) can restore fitness to genetically resistant
      bacteria. Our results also point to a new and clinically relevant treatment
      strategy to combat evolution of resistance in multidrug-resistant tuberculosis.
      Thus, by utilizing antagonistic antibiotic interactions, resistance evolution
      could be reduced.

PMID- 27698073
TI  - Disclosure of donor conception in the era of non-anonymity: safeguarding and
      promoting the interests of donor-conceived individuals?
AB  - This article responds to a debate article published in Human Reproduction earlier
      this year. In that article, the authors suggested that parents should be
      encouraged to disclose the use of donor gametes to their children given rapid and
      widespread advances in genetic testing and sequencing. However, there is an
      urgent need to engage with the assertion that in this context, telling children
      about their donor conception both safeguards and promotes their interests,
      particularly if such disclosure is motivated by parents' anxieties about
      accidental discovery. Disclosure that is motivated by the notion of non-anonymity
      may also encourage parents to share misinformation about donors and encourage
      their children to have unrealistic expectations. Fertility professionals must
      remain mindful of these outcomes when discussing disclosure and the future
      implications of increasing access to genetic information with both prospective
      and current parents. It is strongly advised that future discussions about the end
      of donor anonymity are not conflated with the debate on disclosure.

PMID- 27698072
TI  - Rating Communication in GP Consultations: The Association Between Ratings Made by
      Patients and Trained Clinical Raters.
AB  - Patient evaluations of physician communication are widely used, but we know
      little about how these relate to professionally agreed norms of communication
      quality. We report an investigation into the association between patient
      assessments of communication quality and an observer-rated measure of
      communication competence. Consent was obtained to video record consultations with
      Family Practitioners in England, following which patients rated the physician's
      communication skills. A sample of consultation videos was subsequently evaluated
      by trained clinical raters using an instrument derived from the Calgary-Cambridge
      guide to the medical interview. Consultations scored highly for communication by
      clinical raters were also scored highly by patients. However, when clinical
      raters judged communication to be of lower quality, patient scores ranged from
      "poor" to "very good." Some patients may be inhibited from rating poor
      communication negatively. Patient evaluations can be useful for measuring
      relative performance of physicians' communication skills, but absolute scores
      should be interpreted with caution.

PMID- 27698075
TI  - 'Noisy, restless and incoherent': puerperal insanity at Dundee Lunatic Asylum.
AB  - Puerperal insanity has been described as a nineteenth-century diagnosis,
      entrenched in contemporary expectations of proper womanly behaviour. Drawing on
      detailed study of establishment registers and patient case notes, this paper
      examines the puerperal insanity diagnosis at Dundee Lunatic Asylum between 1820
      and 1860. In particular, the study aims to consider whether the class or social
      status of the patients had a bearing on how their conditions were perceived and
      rationalized, and how far the puerperal insanity diagnosis, coloured by the
      values assigned to it by the medical officers, may have been reserved for some
      women and not for others. This examination of the diagnosis in a Scottish
      community, suggesting a contrast in the way that middle-class and working-class
      women were diagnosed at Dundee, engages with and expands on work on puerperal
      insanity elsewhere.

PMID- 27698074
TI  - Successful IVF pregnancy despite inadequate ovarian steroidogenesis due to
      congenital lipoid adrenal hyperplasia (CLAH): a case report.
AB  - Steroidogenic acute regulatory protein (StAR) mutations are the most frequent
      aetiologies of congenital lipoid adrenal hyperplasia (CLAH). Phenotypes may vary,
      and puberty may be absent in affected individuals. To date, only two pregnancies
      have been described in 46,XX CLAH patients with StAR mutations; these patients
      exhibited ovarian steroidogenesis along with spontaneous puberty and menarche and
      normal menses. The patient described here presented with CLAH caused by the
      homozygous (unreported, 1 bp) deletion c.719del in the StAR gene, which was
      diagnosed after acute adrenal insufficiency when the patient was 10 days old. The
      patient did not undergo spontaneous puberty, so puberty was induced by HRT when
      the patient was 13 years old. At the age of 25 years, the patient was referred to
      our reproductive unit because she desired to conceive. An initial cycle of
      clomiphene, stimulation produced follicular growth with two mature follicles
      measuring 18 and 15 mm, respectively, but the plasma oestradiol levels remained
      low (18 pg/ml) and the endometrium was thin (3 mm). Pregnancy was finally
      achieved after ovarian stimulation, IVF and transfer of frozen-thawed embryos
      after endometrial preparation with HRT. A normal female child was delivered
      following a 40 weeks' uneventful pregnancy. We therefore report the first IVF
      pregnancy achieved in a 46,XX CLAH patient homozygous for a StAR mutation, with
      inadequate ovarian steroidogenesis and no spontaneous puberty.

PMID- 27698076
TI  - Stillbirth: the impact of antiphospholipid syndrome?
AB  - Fetal death resulting in stillbirth is generally acknowledged as a feature of
      antiphospholipid syndrome. Recently published studies appear to confirm the
      association between antiphospholipid antibodies (aPL) and stillbirth, though
      additional studies of better design would be welcome. Emerging evidence suggests
      that treatment with heparin agents and low dose aspirin to prevent fetal death is
      imperfect. New therapeutic approaches for patients with lupus anticoagulant or
      triple aPL positivity are needed.

PMID- 27698078
TI  - Ivabradine: Do the Benefits Outweigh the Risks?
AB  - Ivabradine is a selective I f current inhibitor that is used to lower the heart
      rate (HR) of patients with angina and/or heart failure. It is approved for use in
      several countries, including the United Kingdom, Australia, Saudi Arabia, and the
      United States. The drug was studied in several clinical trials, and it exhibited
      beneficial effects on the approved indicators. However, there are some concerns
      with the safety profile of this drug, especially its effect in reducing HR and
      causing severe bradycardia. Therefore, the current review assessed the benefit
      risk balance of ivabradine. A literature review of the major published studies
      that assessed the efficacy and safety of ivabradine was performed. The online
      VigiBase adverse drug reaction (ADR) reporting system was also accessed to
      investigate reports associated with this drug. A full benefit-risk assessment was
      performed using the collected data from the above-mentioned resources. Most of
      the reviewed studies concluded that ivabradine exerted beneficial effects with a
      tolerable safety profile. Specifically, a favorable benefit-risk profile was
      found when ivabradine was used for patients with an HR >=70 beats per minute.
      Reports revealed that the most common ADR was bradycardia, which was expected.
      Other safety risks or ADRs were comparable to other prescribed drugs. This review
      presents an up-to-date analysis of ivabradine from the latest literature and
      reports. These studies suggest that ivabradine exhibits an acceptable and
      favorable benefit-risk profile, and this drug should be considered as a viable
      option in patients with angina pectoris and chronic heart failure.

PMID- 27698077
TI  - Src Family Kinases Are Regulated in Multiple Myeloma Cells by Phosphatase of
      Regenerating Liver-3.
AB  - : Phosphatase of regenerating liver-3 (PTP4A3/PRL-3) is a dual-specificity
      phosphatase that is upregulated in various types of cancers and is related to
      poor prognosis and aggressive tumor behavior. The expression level of PRL-3 is
      elevated in response to several antiapoptotic cytokines, including IL6, in cancer
      cells from patients with multiple myeloma (MM) and can promote survival and
      migration. Here, it is demonstrated that PRL-3 activates Src kinase in the IL6
      dependent MM cell line INA-6. Inhibition of PRL-3 by a small-molecule inhibitor
      of PRL-3 or by shRNA resulted in inactivation of Src. In addition to activation
      of Src, PRL-3 also activated the Src family kinase (SFK) members LYN and HCK in
      INA-6 cells. Forced expression of catalytically inactive mutant PRL-3 decreased
      the activation of these three SFK members while the total level of HCK and FYN
      remained elevated. Inhibitors of Src increased sensitivity of cells
      overexpressing PRL-3 to the PRL-3 inhibitor through joint downregulation of both
      PRL-3 and Mcl-1. In conclusion, PRL-3 protected MM cells against apoptosis by
      dysregulating both the total levels and the activation levels of specific SFK
      members that are important for IL6 signal transduction in MM cells. Eventually,
      this led to increased levels of Mcl-1. IMPLICATIONS: This study suggests PRL-3
      and SFKs are key mediators of the IL6-driven signaling events and points to both
      PRL-3 and SFK members as potential targets for treatment of MM. Mol Cancer Res;
      15(1); 69-77. (c)2016 AACR.

PMID- 27698079
TI  - Side Effects of CV Medications Following Hospitalization for ACS Are Associated
      With More Frequent Health-Care Contacts.
AB  - BACKGROUND: Patients hospitalized for first acute coronary syndrome (ACS) are
      frequently discharged on multiple new medications. The short-term tolerability of
      these medications is unknown. METHODS: This single-center cohort study assessed
      30-day health-care utilization and how it may be impacted by medication
      prescribing trends. We included Olmsted County patients presenting with ACS and
      previously undiagnosed coronary artery disease in 2008 to 2009. All health-care
      contacts were reviewed 30 days after index hospital discharge for potential
      adverse medication effects including documented hypotension or bradycardia, or
      symptoms likely attributed to the medications. RESULTS: The study included 86
      patients; their mean age was 63 (standard deviation: 15.5 years). Antianginal or
      antihypertensive cardiovascular (CV) medications were prescribed to 98% of
      patients at discharge; 76% were prescribed 2 or more. There were 233 health-care
      contacts in 30 days; 90 (39%) of these contacts were unscheduled. More CV
      medications tended to be prescribed to patients with unscheduled contacts, both
      pre-ACS ( P = .045) and upon hospital discharge ( P = .051). Hypotension and/or
      bradycardia at follow-up occurred in 52 patients (60%). Surprisingly, there was
      no association between hypotension and/or bradycardia at follow-up and increased
      health-care utilization ( P = .12). Potential adverse drug effects were reported
      in 34 (40%) patients. These patients had significantly more total health-care
      contacts ( P < .001) and unscheduled health-care contacts (median 0 vs 1.5; P <
      .001). CONCLUSIONS: Symptoms of adverse drug effects were associated with more
      frequent health-care utilization after ACS. Clinicians need to consider this
      while striving to increase patient compliance with post-ACS medications and
      optimize care transitions.

PMID- 27698080
TI  - Tyrosine Kinase Receptor Expression in Canine Liposarcoma.
AB  - The expression of tyrosine kinase receptors is attracting major interest in human
      and veterinary oncological pathology because of their role as targets for
      adjuvant therapies. Little is known about tyrosine kinase receptor (TKR)
      expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this
      study was to evaluate the immunohistochemical expression of the TKRs fibroblast
      growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor-beta
      (PDGFRbeta); their ligands, fibroblast growth factor 2 (FGF2) and platelet
      derived growth factor B (PDGFB); and c-kit in canine LP. Immunohistochemical
      labeling was categorized as high or low expression and compared with the mitotic
      count and MIB-1-based proliferation index. Fifty canine LPs were examined,
      classified, and graded. Fourteen cases were classified as well differentiated, 7
      as myxoid, 25 as pleomorphic, and 4 as dedifferentiated. Seventeen cases were
      grade 1, 26 were grade 2, and 7 were grade 3. A high expression of FGF2, FGFR1,
      PDGFB, and PDGFRbeta was identified in 62% (31/50), 68% (34/50), 81.6% (40/49),
      and 70.8% (34/48) of the cases, respectively. c-kit was expressed in 12.5% (6/48)
      of the cases. Mitotic count negatively correlated with FGF2 ( R = -0.41; P <
      .01), being lower in cases with high FGF2 expression, and positively correlated
      with PDGFRbeta ( R = 0.33; P < .01), being higher in cases with high PDGFRbeta
      expression. No other statistically significant correlations were identified.
      These results suggest that the PDGFRbeta-mediated pathway may have a role in the
      progression of canine LP and may thus represent a promising target for adjuvant
      cancer therapies.

PMID- 27698081
TI  - The Small RNA GcvB Promotes Mutagenic Break Repair by Opposing the Membrane
      Stress Response.
AB  - : Microbes and human cells possess mechanisms of mutagenesis activated by stress
      responses. Stress-inducible mutagenesis mechanisms may provide important models
      for mutagenesis that drives host-pathogen interactions, antibiotic resistance,
      and possibly much of evolution generally. In Escherichia coli, repair of DNA
      double-strand breaks is switched to a mutagenic mode, using error-prone DNA
      polymerases, via the SOS DNA damage and general (sigmaS) stress responses. We
      investigated small RNA (sRNA) clients of Hfq, an RNA chaperone that promotes
      mutagenic break repair (MBR), and found that GcvB promotes MBR by allowing a
      robust sigmaS response, achieved via opposing the membrane stress (sigmaE)
      response. Cells that lack gcvB were MBR deficient and displayed reduced sigmaS
      dependent transcription but not reduced sigmaS protein levels. The defects in MBR
      and sigmaS-dependent transcription in DeltagcvB cells were alleviated by
      artificially increasing sigmaS levels, implying that GcvB promotes mutagenesis by
      allowing a normal sigmaS response. DeltagcvB cells were highly induced for the
      sigmaE response, and blocking sigmaE response induction restored both mutagenesis
      and sigmaS-promoted transcription. We suggest that GcvB may promote the sigmaS
      response and mutagenesis indirectly, by promoting membrane integrity, which keeps
      sigmaE levels lower. At high levels, sigmaE might outcompete sigmaS for binding
      RNA polymerase and so reduce the sigmaS response and mutagenesis. The data show
      the delicate balance of stress response modulation of mutagenesis. IMPORTANCE:
      Mutagenesis mechanisms upregulated by stress responses promote de novo antibiotic
      resistance and cross-resistance in bacteria, antifungal drug resistance in
      yeasts, and genome instability in cancer cells under hypoxic stress. This paper
      describes the role of a small RNA (sRNA) in promoting a stress-inducible
      mutagenesis mechanism, mutagenic DNA break repair in Escherichia coli The roles
      of many sRNAs in E. coli remain unknown. This study shows that DeltagcvB cells,
      which lack the GcvB sRNA, display a hyperactivated membrane stress response and
      reduced general stress response, possibly because of sigma factor competition for
      RNA polymerase. This results in a mutagenic break repair defect. The data
      illuminate a function of GcvB sRNA in opposing the membrane stress response, and
      thus indirectly upregulating mutagenesis.

PMID- 27698082
TI  - The Phosphorolytic Exoribonucleases Polynucleotide Phosphorylase and RNase PH
      Stabilize sRNAs and Facilitate Regulation of Their mRNA Targets.
AB  - : Gene regulation by base pairing between small noncoding RNAs (sRNAs) and their
      mRNA targets is an important mechanism that allows bacteria to maintain
      homeostasis and respond to dynamic environments. In Gram-negative bacteria, sRNA
      pairing and regulation are mediated by several RNA-binding proteins, including
      the sRNA chaperone Hfq and polynucleotide phosphorylase (PNPase). PNPase and its
      homolog RNase PH together represent the two 3' to 5' phosphorolytic
      exoribonucleases found in Escherichia coli; however, the role of RNase PH in sRNA
      regulation has not yet been explored and reported. Here, we have examined in
      detail how PNPase and RNase PH interact to support sRNA stability, activity, and
      base pairing in exponential and stationary growth conditions. Our results
      indicate that these proteins facilitate the stability and regulatory function of
      the sRNAs RyhB, CyaR, and MicA during exponential growth. PNPase further appears
      to contribute to pairing between RyhB and its mRNA targets. During stationary
      growth, each sRNA responded differently to the absence or presence of PNPase and
      RNase PH. Finally, our results suggest that PNPase and RNase PH stabilize only
      Hfq-bound sRNAs. Taken together, these results confirm and extend previous
      findings that PNPase participates in sRNA regulation and reveal that RNase PH
      serves a similar, albeit more limited, role as well. These proteins may,
      therefore, act to protect sRNAs from spurious degradation while also facilitating
      regulatory pairing with their targets. IMPORTANCE: In many bacteria, Hfq
      dependent base-pairing sRNAs facilitate rapid changes in gene expression that are
      critical for maintaining homeostasis and responding to stress and environmental
      changes. While a role for Hfq in this process was identified more than 2 decades
      ago, the identity and function of the other proteins required for Hfq-dependent
      regulation by sRNAs have not been resolved. Here, we demonstrate that PNPase and
      RNase PH, the two phosphorolytic RNases in E. coli, stabilize sRNAs against
      premature degradation and, in the case of PNPase, also accelerate regulation by
      sRNA-mRNA pairings for certain sRNAs. These findings are the first to demonstrate
      that RNase PH influences and supports sRNA regulation and suggest shared and
      distinct roles for these phosphorolytic RNases in this process.

PMID- 27698083
TI  - The Catabolite Repressor Protein-Cyclic AMP Complex Regulates csgD and Biofilm
      Formation in Uropathogenic Escherichia coli.
AB  - The extracellular matrix protects Escherichia coli from immune cells, oxidative
      stress, predation, and other environmental stresses. Production of the E. coli
      extracellular matrix is regulated by transcription factors that are tuned to
      environmental conditions. The biofilm master regulator protein CsgD upregulates
      curli and cellulose, the two major polymers in the extracellular matrix of
      uropathogenic E. coli (UPEC) biofilms. We found that cyclic AMP (cAMP) regulates
      curli, cellulose, and UPEC biofilms through csgD The alarmone cAMP is produced by
      adenylate cyclase (CyaA), and deletion of cyaA resulted in reduced extracellular
      matrix production and biofilm formation. The catabolite repressor protein (CRP)
      positively regulated csgD transcription, leading to curli and cellulose
      production in the UPEC isolate, UTI89. Glucose, a known inhibitor of CyaA
      activity, blocked extracellular matrix formation when added to the growth medium.
      The mutant strains DeltacyaA and Deltacrp did not produce rugose biofilms,
      pellicles, curli, cellulose, or CsgD. Three putative CRP binding sites were
      identified within the csgD-csgB intergenic region, and purified CRP could gel
      shift the csgD-csgB intergenic region. Additionally, we found that CRP binded
      upstream of kpsMT, which encodes machinery for K1 capsule production. Together
      our work shows that cAMP and CRP influence E. coli biofilms through
      transcriptional regulation of csgD IMPORTANCE The catabolite repressor protein
      (CRP)-cyclic AMP (cAMP) complex influences the transcription of ~7% of genes on
      the Escherichia coli chromosome (D. Zheng, C. Constantinidou, J. L. Hobman, and
      S. D. Minchin, Nucleic Acids Res 32:5874-5893, 2004,
      https://dx.doi.org/10.1093/nar/gkh908). Glucose inhibits E. coli biofilm
      formation, and DeltacyaA and Deltacrp mutants show impaired biofilm formation (D.
      W. Jackson, J.W. Simecka, and T. Romeo, J Bacteriol 184:3406-3410, 2002,
      https://dx.doi.org/10.1128/JB.184.12.3406-3410.2002). We determined that the cAMP
      CRP complex regulates curli and cellulose production and the formation of rugose
      and pellicle biofilms through csgD Additionally, we propose that cAMP may work as
      a signaling compound for uropathogenic E. coli (UPEC) to transition from the
      bladder lumen to inside epithelial cells for intracellular bacterial community
      formation through K1 capsule regulation.

PMID- 27698084
TI  - Aag Hypoxanthine-DNA Glycosylase Is Synthesized in the Forespore Compartment and
      Involved in Counteracting the Genotoxic and Mutagenic Effects of Hypoxanthine and
      Alkylated Bases in DNA during Bacillus subtilis Sporulation.
AB  - : Aag from Bacillus subtilis has been implicated in in vitro removal of
      hypoxanthine and alkylated bases from DNA. The regulation of expression of aag in
      B. subtilis and the resistance to genotoxic agents and mutagenic properties of an
      Aag-deficient strain were studied here. A strain with a transcriptional aag-lacZ
      fusion expressed low levels of beta-galactosidase during growth and early
      sporulation but exhibited increased transcription during late stages of this
      developmental process. Notably, aag-lacZ expression was higher inside the
      forespore than in the mother cell compartment, and this expression was abolished
      in a sigG-deficient background, suggesting a forespore-specific mechanism of aag
      transcription. Two additional findings supported this suggestion: (i) expression
      of an aag-yfp fusion was observed in the forespore, and (ii) in vivo mapping of
      the aag transcription start site revealed the existence of upstream regulatory
      sequences possessing homology to sigmaG-dependent promoters. In comparison with
      the wild-type strain, disruption of aag significantly reduced survival of
      sporulating B. subtilis cells following nitrous acid or methyl methanesulfonate
      treatments, and the Rifr mutation frequency was significantly increased in an aag
      strain. These results suggest that Aag protects the genome of developing B.
      subtilis sporangia from the cytotoxic and genotoxic effects of base deamination
      and alkylation. IMPORTANCE: In this study, evidence is presented revealing that
      aag, encoding a DNA glycosylase implicated in processing of hypoxanthine and
      alkylated DNA bases, exhibits a forespore-specific pattern of gene expression
      during B. subtilis sporulation. Consistent with this spatiotemporal mode of
      expression, Aag was found to protect the sporulating cells of this microorganism
      from the noxious and mutagenic effects of base deamination and alkylation.

PMID- 27698085
TI  - Intracellular d-Serine Accumulation Promotes Genetic Diversity via Modulated
      Induction of RecA in Enterohemorrhagic Escherichia coli.
AB  - : We recently discovered that exposure of enterohemorrhagic Escherichia coli
      (EHEC) to d-serine resulted in accumulation of this unusual amino acid, induction
      of the SOS regulon, and downregulation of the type III secretion system that is
      essential for efficient colonization of the host. Here, we have investigated the
      physiological relevance of this elevated SOS response, which is of particular
      interest given the presence of Stx toxin-carrying lysogenic prophages on the EHEC
      chromosome that are activated during the SOS response. We found that RecA
      elevation in response to d-serine, while being significant, was heterogeneous and
      not capable of activating stx expression or stx phage transduction to a
      nonlysogenic recipient. This "SOS-like response" was, however, capable of
      increasing the mutation frequency associated with low-level RecA activity, thus
      promoting genetic diversity. Furthermore, this response was entirely dependent on
      RecA and enhanced in the presence of a DNA-damaging agent, indicating a
      functional SOS response, but did not result in observable cleavage of the LexA
      repressor alone, indicating a controlled mechanism of induction. This work
      demonstrates that environmental factors not usually associated with DNA damage
      are capable of promoting an SOS-like response. We propose that this modulated
      induction of RecA allows EHEC to adapt to environmental insults such as d-serine
      while avoiding unwanted phage-induced lysis. IMPORTANCE: The SOS response is a
      global stress network that is triggered by the presence of DNA damage due to
      breakage or stalled replication forks. Activation of the SOS response can trigger
      the replication of lytic bacteriophages and promote genetic diversification
      through error-prone polymerases. We have demonstrated that the host-associated
      metabolite d-serine contributes to Escherichia coli niche specification and
      accumulates inside cells that cannot catabolize it. This results in a modulated
      activation of the SOS antirepressor RecA that is insufficient to trigger lytic
      bacteriophage but capable of increasing the SOS-associated mutation frequency.
      These findings describe how relevant signals not normally associated with DNA
      damage can hijack the SOS response, promoting diversity as E. coli strains adapt
      while avoiding unwanted phage lysis.

PMID- 27698086
TI  - Identification of Functions Affecting Predator-Prey Interactions between
      Myxococcus xanthus and Bacillus subtilis.
AB  - : Soil bacteria engage each other in competitive and cooperative ways to
      determine their microenvironments. In this study, we report the identification of
      a large number of genes required for Myxococcus xanthus to engage Bacillus
      subtilis in a predator-prey relationship. We generated and tested over 6,000
      individual transposon insertion mutants of M. xanthus and found many new factors
      required to promote efficient predation, including the specialized metabolite
      myxoprincomide, an ATP-binding cassette (ABC) transporter permease, and a
      clustered regularly interspaced short palindromic repeat (CRISPR) locus encoding
      bacterial immunity. We also identified genes known to be involved in predation,
      including those required for the production of exopolysaccharides and type IV
      pilus (T4P)-dependent motility, as well as chemosensory and two-component
      systems. Furthermore, deletion of these genes confirmed their role during
      predation. Overall, M. xanthus predation appears to be a multifactorial process,
      with multiple determinants enhancing predation capacity. IMPORTANCE: Soil
      bacteria engage each other in complex environments and utilize multiple traits to
      ensure survival. Here, we report the identification of multiple traits that
      enable a common soil organism, Myxococcus xanthus, to prey upon and utilize
      nutrients from another common soil organism, Bacillus subtilis We mutagenized the
      predator and carried out a screen to identify genes that were required to either
      enhance or diminish capacity to consume prey. We identified dozens of genes
      encoding factors that contribute to the overall repertoire for the predator to
      successfully engage its prey in the natural environment.

PMID- 27698089
TI  - The Utility of Assessing Neck Acne.
AB  - BACKGROUND: Acne grading is an essential component in establishing treatment
      options, but little is known on how neck acne should be incorporated into grading
      scales. OBJECTIVE: Our objective was to explore the prevalence of neck acne and
      determine if its own severity category on an acne global grading scale was
      warranted. METHODS: Acne severity was assessed in 6 categories: face, chest,
      back, anterior upper (AUN), anterior lower neck (ALN), and posterior neck (PN).
      RESULTS: The overall prevalence of neck acne was 49%. Of these, 44% had AUN acne,
      18.5% had ALN acne, and 19.8% had PN acne. AUN and facial acne had a significant
      correlation ( r = 0.37, P < .05). No correlation was seen amongst other areas.
      Males presented with a significantly higher severity of AUN (mean [SD], 1.37
      [1.09]) than females (mean [SD], 0.52 [0.91]), on average. CONCLUSIONS: While
      neck acne has proven to be common amongst those with acne on other areas of the
      body, facial acne can be used as a proxy for classification, as neck severity is
      usually milder.

PMID- 27698088
TI  - Interactions between the Cytoplasmic Domains of PspB and PspC Silence the
      Yersinia enterocolitica Phage Shock Protein Response.
AB  - : The phage shock protein (Psp) system is a widely conserved cell envelope stress
      response that is essential for the virulence of some bacteria, including Yersinia
      enterocolitica Recruitment of PspA by the inner membrane PspB-PspC complex
      characterizes the activated state of this response. The PspB-PspC complex has
      been proposed to be a stress-responsive switch, changing from an OFF to an ON
      state in response to an inducing stimulus. In the OFF state, PspA cannot access
      its binding site in the C-terminal cytoplasmic domain of PspC (PspCCT), because
      this site is bound to PspB. PspC has another cytoplasmic domain at its N-terminal
      end (PspCNT), which has been thought to play a role in maintaining the OFF state,
      because its removal causes constitutive activation. However, until now, this role
      has proved recalcitrant to experimental investigation. Here, we developed a
      combination of approaches to investigate the role of PspCNT in Y. enterocolitica
      Pulldown assays provided evidence that PspCNT mediates the interaction of PspC
      with the C-terminal cytoplasmic domain of PspB (PspBCT) in vitro Furthermore,
      site-specific oxidative cross-linking suggested that a PspCNT-PspBCT interaction
      occurs only under noninducing conditions in vivo Additional experiments indicated
      that mutations in pspC might cause constitutive activation by compromising this
      PspCNT binding site or by causing a conformational disturbance that repositions
      PspCNT in vivo These findings have provided the first insight into the regulatory
      function of the N-terminal cytoplasmic domain of PspC, revealing that its ability
      to participate in an inhibitory complex is essential to silencing the Psp
      response. IMPORTANCE: The phage shock protein (Psp) response has generated
      widespread interest because it is linked to important phenotypes, including
      antibiotic resistance, biofilm formation, and virulence in a diverse group of
      bacteria. Therefore, achieving a comprehensive understanding of how this response
      is controlled at the molecular level has obvious significance. An integral inner
      membrane protein complex is believed to be a critical regulatory component that
      acts as a stress-responsive switch, but some essential characteristics of the
      switch states are poorly understood. This study provides an important advance by
      uncovering a new protein interaction domain within this membrane protein complex
      that is essential to silencing the Psp response in the absence of an inducing
      stimulus.

PMID- 27698090
TI  - An Emerging Risk Factor of Sexual Abuse: The Use of Smartphone Dating
      Applications.
AB  - Smartphone dating applications (apps) have become popular in recent years.
      However, the association between the use of dating apps and sexual abuse remains
      uninvestigated. The aim of this study was to examine the association between
      using dating apps and the sexual abuse of males and females. Six hundred sixty
      six participants were recruited in four universities in Hong Kong in 2015.
      Overall, the 1-year prevalence of sexual abuse was 12.4% (95% confidence interval
      [CI]: [9.8, 14.9]) and the lifetime prevalence was 14.2% (95% CI: [11.5, 16.9]).
      Multiple logistic regressions found that users of dating apps (adjusted odds
      ratio [aOR]: 2.13, p < .05) were more likely to be sexually abused in the past
      year than non-users. Using dating apps was also a risk factor of lifetime sexual
      abuse (aOR: 1.83, p < .05). Our findings suggest that app users should deserve
      more attention in risk assessment, risk stratification, and sexual abuse
      prevention programs.

PMID- 27698087
TI  - Autonomous Replication of the Conjugative Transposon Tn916.
AB  - : Integrative and conjugative elements (ICEs), also known as conjugative
      transposons, are self-transferable elements that are widely distributed among
      bacterial phyla and are important drivers of horizontal gene transfer. Many ICEs
      carry genes that confer antibiotic resistances to their host cells and are
      involved in the dissemination of these resistance genes. ICEs reside in host
      chromosomes but under certain conditions can excise to form a plasmid that is
      typically the substrate for transfer. A few ICEs are known to undergo autonomous
      replication following activation. However, it is not clear if autonomous
      replication is a general property of many ICEs. We found that Tn916, the first
      conjugative transposon identified, replicates autonomously via a rolling-circle
      mechanism. Replication of Tn916 was dependent on the relaxase encoded by orf20 of
      Tn916 The origin of transfer of Tn916, oriT(916), also functioned as an origin of
      replication. Using immunoprecipitation and mass spectrometry, we found that the
      relaxase (Orf20) and the two putative helicase processivity factors (Orf22 and
      Orf23) encoded by Tn916 likely interact in a complex and that the Tn916 relaxase
      contains a previously unidentified conserved helix-turn-helix domain in its N
      terminal region that is required for relaxase function and replication. Lastly,
      we identified a functional single-strand origin of replication (sso) in Tn916
      that we predict primes second-strand synthesis during rolling-circle replication.
      Together these results add to the emerging data that show that several ICEs
      replicate via a conserved, rolling-circle mechanism. IMPORTANCE: Integrative and
      conjugative elements (ICEs) drive horizontal gene transfer and the spread of
      antibiotic resistances in bacteria. ICEs reside integrated in a host genome but
      can excise to create a plasmid that is the substrate for transfer to other cells.
      Here we show that Tn916, an ICE with broad host range, undergoes autonomous
      rolling-circle replication when in the plasmid form. We found that the origin of
      transfer functions as a double-stranded origin of replication and identified a
      single-stranded origin of replication. It was long thought that ICEs do not
      undergo autonomous replication. Our work adds to the evidence that ICEs replicate
      autonomously as part of their normal life cycle and indicates that diverse ICEs
      use the same replicative mechanism.

PMID- 27698091
TI  - Social Class and the Motivational Relevance of Other Human Beings: Evidence From
      Visual Attention.
AB  - We theorize that people's social class affects their appraisals of others'
      motivational relevance-the degree to which others are seen as potentially
      rewarding, threatening, or otherwise worth attending to. Supporting this account,
      three studies indicate that social classes differ in the amount of attention
      their members direct toward other human beings. In Study 1, wearable technology
      was used to film the visual fields of pedestrians on city streets; higher-class
      participants looked less at other people than did lower-class participants. In
      Studies 2a and 2b, participants' eye movements were tracked while they viewed
      street scenes; higher class was associated with reduced attention to people in
      the images. In Study 3, a change-detection procedure assessed the degree to which
      human faces spontaneously attract visual attention; faces proved less effective
      at drawing the attention of high-class than low-class participants, which implies
      that class affects spontaneous relevance appraisals. The measurement and
      conceptualization of social class are discussed.

PMID- 27698092
TI  - "It's Easy to Get Fags": A Qualitative Study of Disadvantaged Young People's
      Perspectives on Cigarette Availability and Access.
AB  - Introduction: Reducing young people's access to cigarettes is a key element of
      smoking prevention policies. This article explores how young people source
      cigarettes following the increase in the UK minimum age of sale from 16 to 18
      years. Methods: Semi-structured individual, paired and triadic interviews with 60
      disadvantaged young people aged between 12 and 17. Participants were recruited
      from clubs and voluntary organizations offering advice and support to
      disadvantaged young people. Results: Most participants said they sourced
      cigarettes from shops, but understandings of "buying cigarettes from shops"
      included using intermediaries for proxy purchases. Access from social sources was
      contingent on reciprocation, and blackmarket sources were avoided. The
      distinction between potential and actual sources reflected participants concerns
      about their presentation of self. Those who bought cigarettes directly from shops
      accrued status and power in negotiating social hierarchies. Participants
      therefore highlighted their smoking related competencies, that is, ability to
      secure regular retail access to tobacco, while downplaying the significant
      difficulties they experienced. Conclusions: The presentational dimension of youth
      cigarette access highlights a need for caution in associating self-reported
      changes in young people's cigarette sources straightforwardly with access
      policies. The conflation of direct retail purchases with proxy purchases, and the
      interrelationship between commercial and social cigarette sources also raises
      issues for interpreting data on "usual" cigarette sources from national surveys.
      Findings suggest that some young people may still be both reliant on making
      retail cigarette purchases following the increase in the age of sale in the
      United Kingdom, and experiencing significant difficulties making these.
      Implications: This study highlights the self-presentational dimension of youth
      cigarette access in a particular community context, and the important distinction
      between the apparent range of sources available and their social acceptability in
      young people's social networks. Young smokers tended to conflate direct retail
      purchases with proxy purchases, raising issues for interpreting survey data on
      "usual" cigarette source. The presentational dimension of youth cigarette access
      also highlights a need for caution in associating self-reported changes in young
      people's cigarette sources with access policies. Despite participants' stated
      easy access, few were able to buy cigarettes directly, underscoring the
      effectiveness of youth access policies.

PMID- 27698094
TI  - Comparison of the Fagerstrom Test for Cigarette Dependence and the Heaviness of
      Smoking Index in the Second and Third Trimester of Pregnancy.
AB  - Introduction: Smoking cessation at any stage of pregnancy can benefit the mother
      and fetus. Cigarette dependence is a significant factor in women who continue to
      smoke during pregnancy and accurate assessment of cigarette dependence can be
      helpful in planning smoking cessation programs. The objective of our study was to
      investigate the validity of the Fagerstrom Test for Cigarette Dependence (FTCD)
      and Heaviness of Smoking Index (HSI) as measures of cigarette dependence in the
      second and third trimesters of pregnancy by comparing them to serum cotinine
      levels. Methods: Prospective cohort study of 167 women in their second and third
      trimester of pregnancy who self-reported cigarette smoking. They were
      administered the FTCD questionnaire and blood was drawn for cotinine measurements
      using a direct enzyme linked immunoassay. Linear regression was used to adjust
      for maternal age, body mass index, gestation, and parity to investigate the
      association between cotinine levels and the two scores. Results: Both the FTCD
      and HSI correlated significantly with serum cotinine levels (Spearman coefficient
      0.42 and 0.37, respectively, p < .001). The correlation coefficients of both
      scores were higher in primigravidas (n = 51) compared to multigravidas, but the
      difference was statistically nonsignificant. Using multiple linear regression,
      both scores were significantly related to serum cotinine levels. For each unit
      increase in the FTCD and HSI, the serum cotinine level increased by 21.4 ng/mL
      (95% confidence interval 10.1-32.7, p <0.001) and 37 ng/mL (95% confidence
      interval 18.6-55.4, p < 0.001), respectively. Conclusions: Both the FTCD and HSI
      can be used to assess cigarette dependence in the second and third trimester of
      pregnancy. Implications: There is lack of data on the validity of the FTCD and
      the HSI as markers of cigarette dependence during the second and third trimester
      of pregnancy. Our study suggests that both the FTCD and HSI perform well in
      assessing cigarette dependence in the second and third trimester of pregnancy and
      can be used to plan smoking cessation programs.

PMID- 27698093
TI  - A Qualitative Study Among Mexican Americans to Understand Factors Influencing the
      Adoption and Enforcement of Home Smoking Bans.
AB  - Introduction: One-third of Mexican-American children, in addition to nonsmoker
      adults, are exposed to secondhand smoke at home, yet few interventions target
      Mexican-American households. An effective, brief English language program, tested
      with United Way 2-1-1 callers in Atlanta, increased home smoking bans (confirmed
      by air monitors). Two randomized controlled trials in North Carolina and Texas
      replicated those results. We explored factors determining adoption and
      enforcement of smoking bans in Mexican-American households to inform program
      linguistic and cultural adaptation to broaden program reach and relevance.
      Methods: Bilingual interviewers recruited convenience samples of Mexican-American
      smokers and nonsmokers living with at least one smoker in Houston and San Diego
      households and asked open-ended questions regarding conditions for implementing
      home and vehicle smoking bans and conditions for varying acceptance of bans.
      Investigators independently reviewed English transcripts and completed a
      descriptive analysis using ATLAS.ti. Results: Participants (n = 43) were
      predominantly female (n = 31), current smokers (n = 26), interviewed in Spanish
      (n = 26), had annual household incomes less than $30000 (n = 24), and allowed
      smoking inside the home (n = 24). Themes related to difficulty creating and
      enforcing bans included courtesy, respect for guests and heads of household who
      smoke, and gender imbalances in decision making. Participants viewed protecting
      children's health as a reason for the ban but not protecting adult nonsmokers'
      health. Conclusion: A dual-language, culturally adapted intervention targeting
      multigenerational Mexican-American households should address household
      differences regarding language and consider influences of cultural values on
      family dynamics and interactions with guests that may weaken bans. Implications:
      Qualitative interviews suggested cultural and family considerations to address in
      adapting a brief evidence-based smoke-free homes intervention for Mexican
      Americans, including traditional gender roles, unique contexts of
      multigenerational households, and language preferences. Our work confirms
      previous research among Latinos regarding importance of common cultural
      constructs, such as respeto (deference), simpatia (courtesy and agreeability),
      and familismo (family attachment), which inform behaviors that may impede or
      facilitate adopting and enforcing home smoking bans. Decision-making gender
      imbalances, high regard for head-of-household and guest smokers, and less
      sensitivity to the health of nonsmoker adults compared with children may lead to
      permission to smoke indoors.

PMID- 27698097
TI  - By the Numbers: Mortality Burden of Heart Disease and Cancer, 1950-2014.
AB  - Although the number of deaths due to heart disease began a relatively steady
      decline in the 1990s, it remains the leading cause of death overall in the United
      States, followed by cancer. However, the gap between them has narrowed greatly
      since 1950, and in 2014, cancer deaths outnumbered deaths due to heart disease in
      22 states.

PMID- 27698099
TI  - BCL2 Inhibition by Venetoclax: Targeting the Achilles' Heel of the Acute Myeloid
      Leukemia Stem Cell?
AB  - Venetoclax is an oral drug with an excellent side-effect profile that has the
      potential to revolutionize acute myeloid leukemia (AML) therapy in two areas.
      Venetoclax-based combination therapies could be a bridge to hematopoietic cell
      transplant with curative intent for patients with refractory/relapsed AML, and
      venetoclax-based therapy could provide meaningful survival prolongation for older
      patients with AML who are not candidates for more aggressive therapies. Cancer
      Discov; 6(10); 1082-3. (c)2016 AACR.See related article by Konopleva and
      colleagues, p. 1106.

PMID- 27698100
TI  - Cracking the Code of Resistance across Multiple Lines of ALK Inhibitor Therapy in
      Lung Cancer.
AB  - In the setting of recent exciting clinical results and numerous ongoing trials,
      Gainor and colleagues explored mechanisms of acquired resistance to first- and
      second-generation ALK inhibitors in ALK-rearranged non-small cell lung cancer and
      found that an increased frequency and distinct spectrums of resistance mutations
      emerged with the more potent second-generation inhibitors. Their findings have
      important and immediate clinical implications as the resistance mutations
      detected impart differential sensitivities to available ALK inhibitors, thereby
      highlighting the need for sequential biopsies with molecular testing to determine
      the most effective treatment strategy upon disease progression. Cancer Discov;
      6(10); 1084-6. (c)2016 AACRSee related article by Gainor et al., p. 1118.

PMID- 27698101
TI  - Accurate Medicine: Indirect Targeting of NPM1-Mutated AML.
AB  - Acute myeloid leukemia (AML) is now recognized to be an imprecise term that
      refers to a range of myeloid malignancies that have different genetical
      etiologies, clinical characteristics, and therapeutic sensitivities. Targeting
      the MLL1 and DOT1L histone modification complexes, both alone and in combination,
      showed activity against AML driven by a mutant NPM1 protein in several
      preclinical models and may represent a new treatment direction for this
      devastating disease. Cancer Discov; 6(10); 1087-9 (c)2016 AACR.See related
      article by Kuhn and colleagues p. 1166.

PMID- 27698102
TI  - Women's Health and Mindfulness (WHAM): A Randomized Intervention Among Older
      Lesbian/Bisexual Women.
AB  - INTRODUCTION: Lesbian and bisexual (LB) women have higher body weight than
      heterosexual women. Interventions focused on health and well-being versus weight
      loss may be more likely to succeed among LB women. This article describes effects
      of Women's Health and Mindfulness, a 12-week pilot intervention addressing
      mindfulness, healthy eating, and physical activity, on outcomes associated with
      chronic disease risk among overweight and obese LB women older than 40 years.
      METHOD: Eighty women were randomized, using a stepped-wedge design, to either an
      immediate- or a delayed-start intervention group; the delayed-start group served
      as the control. Eligible participants were aged 40 years or older, identified as
      LB, and had a body mass index of 27 or greater. We compared differences in
      biological markers of chronic disease, mindfulness, nutrition, and physical
      activity between immediate- and delayed-start intervention groups. RESULTS: We
      observed clinically significant improvements in low-density lipoprotein
      cholesterol but no change in hemoglobin A1c. We found evidence of intervention
      effects on improved mindfulness and mindful eating scores and on nutrition
      (improved vegetable intake). CONCLUSIONS: The Women's Health and Mindfulness
      pilot intervention appears to have initiated positive behavioral and physical
      health changes in this population. Refinements to the intervention model, such as
      extended intervention duration, and longer term follow-up are warranted to
      determine sustained effects.

PMID- 27698103
TI  - Management of Juvenile Idiopathic Arthritis 2015: A Position Statement from the
      Pediatric Committee of the Canadian Rheumatology Association.

PMID- 27698104
TI  - Rapid Progressive Peripheral Ulcerative Keratitis Associated with Longstanding
      Rheumatoid Arthritis.

PMID- 27698105
TI  - The Role of High-resolution Peripheral Quantitative Computed Tomography as a
      Biomarker for Joint Damage in Inflammatory Arthritis.
AB  - Since 2011, members of the SPECTRA Collaboration (Study grouP for xtrEme-Computed
      Tomography in Rheumatoid Arthritis) have investigated the validity, reliability,
      and responsiveness of high-resolution peripheral quantitative computed tomography
      (HR-pQCT) as a biomarker for joint damage in inflammatory arthritis. Presented in
      this series of articles are a systematic review of HR-pQCT-related findings to
      date, a review of selected images of cortical and subchondral trabecular bone of
      metacarpophalangeal (MCP) joints, results of a consensus process to standardize
      the definition of erosions and their quantification, as well as an examination of
      the effect of joint flexion on width and volume assessment of the joint space.

PMID- 27698106
TI  - Heterogeneity of Cortical Breaks in Hand Joints of Patients with Rheumatoid
      Arthritis and Healthy Controls Imaged by High-resolution Peripheral Quantitative
      Computed Tomography.
AB  - OBJECTIVE: Conventional radiographs (CR) of the hands are the gold standard for
      imaging bone erosions. The presence of bone erosions, reflected by the presence
      of cortical breaks, is a poor prognostic factor in patients with rheumatoid
      arthritis (RA). The availability of high-resolution peripheral quantitative
      computed tomography (HR-pQCT) enables detailed investigation of cortical breaks
      in rheumatic diseases. The aim of this image review is to show HR-pQCT images of
      the spectrum of cortical breaks with and without underlying trabecular bone
      changes in metacarpophalangeal (MCP) joints of healthy controls (HC) and patients
      with RA, with corresponding images on CR and magnetic resonance imaging (MRI).
      METHODS: Second and third MCP joints of 41 patients (of which 10 were early RA
      with <= 2 years and 24 longstanding RA with >= 10 years of disease duration) and
      38 HC were imaged by CR, MRI, and HR-pQCT (XtremeCT1, Scanco Medical AG).
      Representative images of the spectrum of cortical breaks were selected. RESULTS:
      Cortical breaks were found in early and longstanding RA, but also in HC. They
      were heterogeneous in size, location, and number per joint, with a variety of
      surrounding cortical and underlying trabecular bone characteristics. CONCLUSION:
      Using HR-pQCT images of MCP joints, heterogeneous cortical breaks with and
      without surrounding trabecular bone changes were found, not only in RA but also
      in HC. The underlying mechanisms and significance of this spectrum of cortical
      breaks as found with high 3-D resolution needs further investigation.

PMID- 27698107
TI  - High-resolution Peripheral Quantitative Computed Tomography Imaging in the
      Assessment of Periarticular Bone of Metacarpophalangeal and Wrist Joints.
AB  - OBJECTIVE: To synthesize descriptions of periarticular findings at the
      metacarpophalangeal (MCP) and wrist joints in different types of arthritis and in
      the normal state imaged by high-resolution peripheral quantitative computed
      tomography (HR-pQCT); to assemble the literature reporting on the ability of HR
      pQCT to detect findings relative to other imaging modalities; and to collate
      results on the reproducibility of image interpretation. METHODS: A systematic
      literature review was performed using terms for HR-pQCT and MCP or wrist joints
      using medical literature databases and conference abstracts. Any study describing
      predefined pathology findings, comparison to another radiographic technique, or a
      measure of reproducibility was included with no limitation by disease state.
      RESULTS: We identified 44 studies meeting inclusion criteria from the 1901
      articles identified by our search. All 44 reported on pathology findings,
      including erosions (n = 31), bone microarchitecture (n = 10) and bone mineral
      density (n = 10) variables, joint space evaluation (n = 7), or osteophyte
      characterization (n = 7). Seventeen of the studies compared HR-pQCT findings to
      either plain radiography (n = 9), ultrasound (n = 4), magnetic resonance imaging
      (n = 5), or microcomputed tomography (n = 2), with HR-pQCT having high
      sensitivity for erosion detection. Twenty-four studies included an assessment of
      reproducibility with good to excellent metrics, and highlighting the critical
      importance of positioning when assessing joint space variables. CONCLUSION:
      Despite high sensitivity for erosion detection and good reproducibility, more
      research is required to determine where HR-pQCT can be applied to enhance our
      understanding of periarticular bone changes in a variety of arthritis conditions.

PMID- 27698109
TI  - Determining Metacarpophalangeal Flexion Angle Tolerance for Reliable Volumetric
      Joint Space Measurements by High-resolution Peripheral Quantitative Computed
      Tomography.
AB  - OBJECTIVE: The position-dependence of a method to measure the joint space of
      metacarpophalangeal (MCP) joints using high-resolution peripheral quantitative
      computed tomography (HR-pQCT) was studied. METHODS: Cadaveric MCP were imaged at
      7 flexion angles between 0 and 30 degrees. The variability in reproducibility for
      mean, minimum, and maximum joint space widths and volume measurements was
      calculated for increasing degrees of flexion. RESULTS: Root mean square
      coefficient of variance values were < 5% under 20 degrees of flexion for mean,
      maximum, and volumetric joint spaces. Values for minimum joint space width were
      optimized under 10 degrees of flexion. CONCLUSION: MCP joint space measurements
      should be acquired at < 10 degrees of flexion in longitudinal studies.

PMID- 27698108
TI  - Definition for Rheumatoid Arthritis Erosions Imaged with High Resolution
      Peripheral Quantitative Computed Tomography and Interreader Reliability for
      Detection and Measurement.
AB  - OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT)
      sensitively detects erosions in rheumatoid arthritis (RA); however,
      nonpathological cortical bone disruptions are potentially misclassified as
      erosive. Our objectives were to set and test a definition for pathologic cortical
      bone disruptions in RA and to standardize reference landmarks for measuring
      erosion size. METHODS: HR-pQCT images of metacarpophalangeal joints of RA and
      control subjects were used in an iterative process to achieve consensus on the
      definition and reference landmarks. Independent readers (n = 11) applied the
      definition to score 58 joints and measure pathologic erosions in 2 perpendicular
      multiplanar reformations for their maximum width and depth. Interreader
      reliability for erosion detection and variability in measurements between readers
      [root mean square coefficient of variation (RMSCV), intraclass correlation (ICC)]
      were calculated. RESULTS: Pathologic erosions were defined as cortical breaks
      extending over a minimum of 2 consecutive slices in perpendicular planes, with
      underlying trabecular bone loss and a nonlinear shape. Interreader agreement for
      classifying pathologic erosions was 90.2%, whereas variability for width and
      depth erosion assessment was observed (RMSCV perpendicular width 12.3%, axial
      width 20.6%, perpendicular depth 24.0%, axial depth 22.2%; ICC perpendicular
      width 0.206, axial width 0.665, axial depth 0.871, perpendicular depth 0.783).
      Mean erosion width was 1.84 mm (range 0.16-8.90) and mean depth was 1.86 mm
      (range 0.30-8.00). CONCLUSION: We propose a new definition for erosions
      visualized with HR-pQCT imaging. Interreader reliability for erosion detection is
      good, but further refinement of selection of landmarks for erosion size
      measurement, or automated volumetric methods, will be pursued.

PMID- 27698110
TI  - Arthralgia Associated with Autoimmune Abnormalities under Aromatase Inhibitor
      Therapy: Outcome after Cessation of Treatment.

PMID- 27698111
TI  - A case of perimenopausal depression.

PMID- 27698112
TI  - Wnt/beta-catenin signaling promotes self-renewal and inhibits the primed state
      transition in naive human embryonic stem cells.
AB  - In both mice and humans, pluripotent stem cells (PSCs) exist in at least two
      distinct states of pluripotency, known as the naive and primed states. Our
      understanding of the intrinsic and extrinsic factors that enable PSCs to self
      renew and to transition between different pluripotent states is important for
      understanding early development. In mouse embryonic stem cells (mESCs), Wnt
      proteins stimulate mESC self-renewal and support the naive state. In human
      embryonic stem cells (hESCs), Wnt/beta-catenin signaling is active in naive-state
      hESCs and is reduced or absent in primed-state hESCs. However, the role of
      Wnt/beta-catenin signaling in naive hESCs remains largely unknown. Here, we
      demonstrate that inhibition of the secretion of Wnts or inhibition of the
      stabilization of beta-catenin in naive hESCs reduces cell proliferation and
      colony formation. Moreover, we show that addition of recombinant Wnt3a partially
      rescues cell proliferation in naive hESCs caused by inhibition of Wnt secretion.
      Notably, inhibition of Wnt/beta-catenin signaling in naive hESCs did not cause
      differentiation. Instead, it induced primed hESC-like proteomic and metabolic
      profiles. Thus, our results suggest that naive hESCs secrete Wnts that activate
      autocrine or paracrine Wnt/beta-catenin signaling to promote efficient self
      renewal and inhibit the transition to the primed state.

PMID- 27698113
TI  - Clonal expansion of CD8 T cells in the systemic circulation precedes development
      of ipilimumab-induced toxicities.
AB  - Immune checkpoint therapies, such as ipilimumab, induce dramatic antitumor
      responses in a subset of patients with advanced malignancies, but they may also
      induce inflammatory responses and toxicities termed immune-related adverse events
      (irAEs). These irAEs are often low grade and manageable, but severe irAEs may
      lead to prolonged hospitalizations or fatalities. Early intervention is necessary
      to minimize morbidities that occur with severe irAEs. However, correlative
      biomarkers are currently lacking. In a phase II clinical trial that treated 27
      patients with metastatic prostate cancer, we aimed to test the safety and
      efficacy of androgen deprivation therapy plus ipilimumab. In this study, we
      observed grade 3 toxicities in >40% of treated patients, which led to early
      closure of the study. Because ipilimumab enhances T-cell responses, we
      hypothesized that increased clonal T-cell responses in the systemic circulation
      may contribute to irAEs. Sequencing of the T-cell receptor beta-chains in
      purified T cells revealed clonal expansion of CD8 T cells, which occurred in
      blood samples collected before the onset of grade 2-3 irAEs. These initial
      results suggested that expansion of >=55 CD8 T-cell clones preceded the
      development of severe irAEs. We further evaluated available blood samples from a
      second trial and determined that patients who experienced grade 2-3 irAEs also
      had expansion of >=55 CD8 T-cell clones in blood samples collected before the
      onset of irAEs. We propose that CD8 T-cell clonal expansion may be a correlative
      biomarker to enable close monitoring and early intervention for patients
      receiving ipilimumab.

PMID- 27698116
TI  - Equatorial heat accumulation as a long-term trigger of permanent Antarctic ice
      sheets during the Cenozoic.
AB  - Growth of the first permanent Antarctic ice sheets at the Eocene-Oligocene
      Transition (EOT), ~33.7 million years ago, indicates a major climate shift within
      long-term Cenozoic cooling. The driving mechanisms that set the stage for this
      glaciation event are not well constrained, however, owing to large uncertainties
      in temperature reconstructions during the Eocene, especially at lower latitudes.
      To address this deficiency, we used recent developments in coccolith
      biogeochemistry to reconstruct equatorial Atlantic sea surface temperature (SST)
      and atmospheric pCO2 values from pelagic sequences preceding and spanning the
      EOT. We found significantly more variability in equatorial SSTs than previously
      reported, with pronounced cooling from the Early to Middle Eocene and subsequent
      warming during the Late Eocene. Thus, we show that the Antarctic glaciation at
      the Eocene-Oligocene boundary was preceded by a period of heat accumulation in
      the low latitudes, likely focused in a progressively contracting South Atlantic
      gyre, which contributed to cooling high-latitude austral regions. This prominent
      redistribution of heat corresponds to the emplacement of a strong meridional
      temperature gradient that typifies icehouse climate conditions. Our equatorial
      coccolith-derived geochemical record thus highlights an important period of
      global climatic and oceanic upheaval, which began 4 million years before the EOT
      and, superimposed on a long-term pCO2 decline, drove the Earth system toward a
      glacial tipping point in the Cenozoic.

PMID- 27698114
TI  - eIF2alpha phosphorylation controls thermal nociception.
AB  - A response to environmental stress is critical to alleviate cellular injury and
      maintain cellular homeostasis. Eukaryotic initiation factor 2 (eIF2) is a key
      integrator of cellular stress responses and an important regulator of mRNA
      translation. Diverse stress signals lead to the phosphorylation of the alpha
      subunit of eIF2 (Ser51), resulting in inhibition of global protein synthesis
      while promoting expression of proteins that mediate cell adaptation to stress.
      Here we report that eIF2alpha is instrumental in the control of noxious heat
      sensation. Mice with decreased eIF2alpha phosphorylation (eIF2alpha+/S51A)
      exhibit reduced responses to noxious heat. Pharmacological attenuation of
      eIF2alpha phosphorylation decreases thermal, but not mechanical, pain
      sensitivity, whereas increasing eIF2alpha phosphorylation has the opposite effect
      on thermal nociception. The impact of eIF2alpha phosphorylation (p-eIF2alpha) on
      thermal thresholds is dependent on the transient receptor potential vanilloid 1.
      Moreover, we show that induction of eIF2alpha phosphorylation in primary sensory
      neurons in a chronic inflammation pain model contributes to thermal
      hypersensitivity. Our results demonstrate that the cellular stress response
      pathway, mediated via p-eIF2alpha, represents a mechanism that could be used to
      alleviate pathological heat sensation.

PMID- 27698115
TI  - An evolutionarily conserved element in initiator tRNAs prompts ultimate steps in
      ribosome maturation.
AB  - Ribosome biogenesis, a complex multistep process, results in correct folding of
      rRNAs, incorporation of >50 ribosomal proteins, and their maturation.
      Deficiencies in ribosome biogenesis may result in varied faults in translation of
      mRNAs causing cellular toxicities and ribosomopathies in higher organisms. How
      cells ensure quality control in ribosome biogenesis for the fidelity of its
      complex function remains unclear. Using Escherichia coli, we show that initiator
      tRNA (i-tRNA), specifically the evolutionarily conserved three consecutive GC
      base pairs in its anticodon stem, play a crucial role in ribosome maturation.
      Deficiencies in cellular contents of i-tRNA confer cold sensitivity and result in
      accumulation of ribosomes with immature 3' and 5' ends of the 16S rRNA.
      Overexpression of i-tRNA in various strains rescues biogenesis defects.
      Participation of i-tRNA in the first round of initiation complex formation
      licenses the final steps of ribosome maturation by signaling RNases to trim the
      terminal extensions of immature 16S rRNA.

PMID- 27698117
TI  - Regulation of MIR165/166 by class II and class III homeodomain leucine zipper
      proteins establishes leaf polarity.
AB  - A defining feature of plant leaves is their flattened shape. This shape depends
      on an antagonism between the genes that specify adaxial (top) and abaxial
      (bottom) tissue identity; however, the molecular nature of this antagonism
      remains poorly understood. Class III homeodomain leucine zipper (HD-ZIP)
      transcription factors are key mediators in the regulation of adaxial-abaxial
      patterning. Their expression is restricted adaxially during early development by
      the abaxially expressed microRNA (MIR)165/166, yet the mechanism that restricts
      MIR165/166 expression to abaxial leaf tissues remains unknown. Here, we show that
      class III and class II HD-ZIP proteins act together to repress MIR165/166 via a
      conserved cis-element in their promoters. Organ morphology and tissue patterning
      in plants, therefore, depend on a bidirectional repressive circuit involving a
      set of miRNAs and its targets.

PMID- 27698119
TI  - Estimates of the magnitudes of major marine mass extinctions in earth history.
AB  - Procedures introduced here make it possible, first, to show that background
      (piecemeal) extinction is recorded throughout geologic stages and substages (not
      all extinction has occurred suddenly at the ends of such intervals); second, to
      separate out background extinction from mass extinction for a major crisis in
      earth history; and third, to correct for clustering of extinctions when using the
      rarefaction method to estimate the percentage of species lost in a mass
      extinction. Also presented here is a method for estimating the magnitude of the
      Signor-Lipps effect, which is the incorrect assignment of extinctions that
      occurred during a crisis to an interval preceding the crisis because of the
      incompleteness of the fossil record. Estimates for the magnitudes of mass
      extinctions presented here are in most cases lower than those previously
      published. They indicate that only ~81% of marine species died out in the great
      terminal Permian crisis, whereas levels of 90-96% have frequently been quoted in
      the literature. Calculations of the latter numbers were incorrectly based on
      combined data for the Middle and Late Permian mass extinctions. About 90 orders
      and more than 220 families of marine animals survived the terminal Permian
      crisis, and they embodied an enormous amount of morphological, physiological, and
      ecological diversity. Life did not nearly disappear at the end of the Permian, as
      has often been claimed.

PMID- 27698121
TI  - Increasing vertical resolution in US models to improve track forecasts of
      Hurricane Joaquin with HWRF as an example.
AB  - The atmosphere-ocean coupled Hurricane Weather Research and Forecast model (HWRF)
      developed at the National Centers for Environmental Prediction (NCEP) is used as
      an example to illustrate the impact of model vertical resolution on track
      forecasts of tropical cyclones. A number of HWRF forecasting experiments were
      carried out at different vertical resolutions for Hurricane Joaquin, which
      occurred from September 27 to October 8, 2015, in the Atlantic Basin. The results
      show that the track prediction for Hurricane Joaquin is much more accurate with
      higher vertical resolution. The positive impacts of higher vertical resolution on
      hurricane track forecasts suggest that National Oceanic and Atmospheric
      Administration/NCEP should upgrade both HWRF and the Global Forecast System to
      have more vertical levels.

PMID- 27698118
TI  - Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic
      responses.
AB  - Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain
      critical barriers to cancer development, the emerging role of p53 in cell
      metabolism, oxidative responses, and ferroptotic cell death has been a topic of
      great interest. Nevertheless, it is unclear how p53 orchestrates its activities
      in multiple metabolic pathways into tumor suppressive effects. Here, we
      identified the SAT1 (spermidine/spermine N1-acetyltransferase 1) gene as a
      transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine
      catabolism critically involved in the conversion of spermidine and spermine back
      to putrescine. Surprisingly, we found that activation of SAT1 expression induces
      lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive
      oxygen species (ROS)-induced stress, which also leads to suppression of tumor
      growth in xenograft tumor models. Notably, SAT1 expression is down-regulated in
      human tumors, and CRISPR-cas9-mediated knockout of SAT1 expression partially
      abrogates p53-mediated ferroptosis. Moreover, SAT1 induction is correlated with
      the expression levels of arachidonate 15-lipoxygenase (ALOX15), and SAT1-induced
      ferroptosis is significantly abrogated in the presence of PD146176, a specific
      inhibitor of ALOX15. Thus, our findings uncover a metabolic target of p53
      involved in ferroptotic cell death and provide insight into the regulation of
      polyamine metabolism and ferroptosis-mediated tumor suppression.

PMID- 27698120
TI  - Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of
      AMPK.
AB  - Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met)
      restriction, extends the lifespan of diverse model organisms. Although studies
      have identified several metabolites that contribute to the beneficial effects of
      DR, the molecular mechanism underlying the key metabolites responsible for DR
      regimens is not fully understood. Here we show that stimulating S-adenosyl-l
      methionine (AdoMet) synthesis extended the lifespan of the budding yeast
      Saccharomyces cerevisiae The AdoMet synthesis-mediated beneficial metabolic
      effects, which resulted from consuming both Met and ATP, mimicked CR. Indeed,
      stimulating AdoMet synthesis activated the universal energy-sensing regulator
      Snf1, which is the S. cerevisiae ortholog of AMP-activated protein kinase (AMPK),
      resulting in lifespan extension. Furthermore, our findings revealed that S
      adenosyl-l-homocysteine contributed to longevity with a higher accumulation of
      AdoMet only under the severe CR (0.05% glucose) conditions. Thus, our data
      uncovered molecular links between Met metabolites and lifespan, suggesting a
      unique function of AdoMet as a reservoir of Met and ATP for cell survival.

PMID- 27698122
TI  - Simple dynamical models capturing the key features of the Central Pacific El
      Nino.
AB  - The Central Pacific El Nino (CP El Nino) has been frequently observed in recent
      decades. The phenomenon is characterized by an anomalous warm sea surface
      temperature (SST) confined to the central Pacific and has different
      teleconnections from the traditional El Nino. Here, simple models are developed
      and shown to capture the key mechanisms of the CP El Nino. The starting model
      involves coupled atmosphere-ocean processes that are deterministic, linear, and
      stable. Then, systematic strategies are developed for incorporating several major
      mechanisms of the CP El Nino into the coupled system. First, simple nonlinear
      zonal advection with no ad hoc parameterization of the background SST gradient is
      introduced that creates coupled nonlinear advective modes of the SST. Secondly,
      due to the recent multidecadal strengthening of the easterly trade wind, a
      stochastic parameterization of the wind bursts including a mean easterly trade
      wind anomaly is coupled to the simple atmosphere-ocean processes. Effective
      stochastic noise in the wind burst model facilitates the intermittent occurrence
      of the CP El Nino with realistic amplitude and duration. In addition to the
      anomalous warm SST in the central Pacific, other major features of the CP El Nino
      such as the rising branch of the anomalous Walker circulation being shifted to
      the central Pacific and the eastern Pacific cooling with a shallow thermocline
      are all captured by this simple coupled model. Importantly, the coupled model
      succeeds in simulating a series of CP El Nino that lasts for 5 y, which resembles
      the two CP El Nino episodes during 1990-1995 and 2002-2006.

PMID- 27698123
TI  - Gate fidelity and coherence of an electron spin in an Si/SiGe quantum dot with
      micromagnet.
AB  - The gate fidelity and the coherence time of a quantum bit (qubit) are important
      benchmarks for quantum computation. We construct a qubit using a single electron
      spin in an Si/SiGe quantum dot and control it electrically via an artificial spin
      orbit field from a micromagnet. We measure an average single-qubit gate fidelity
      of ~99% using randomized benchmarking, which is consistent with dephasing from
      the slowly evolving nuclear spins in the substrate. The coherence time measured
      using dynamical decoupling extends up to ~400 MUs for 128 decoupling pulses, with
      no sign of saturation. We find evidence that the coherence time is limited by
      noise in the 10-kHz to 1-MHz range, possibly because charge noise affects the
      spin via the micromagnet gradient. This work shows that an electron spin in an
      Si/SiGe quantum dot is a good candidate for quantum information processing as
      well as for a quantum memory, even without isotopic purification.

PMID- 27698124
TI  - Regulated large-scale nucleosome density patterns and precise nucleosome
      positioning correlate with V(D)J recombination.
AB  - We show that the physical distribution of nucleosomes at antigen receptor loci is
      subject to regulated cell type-specific and lineage-specific positioning and
      correlates with the accessibility of these gene segments to recombination. At the
      Ig heavy chain locus (IgH), a nucleosome in pro-B cells is generally positioned
      over each IgH variable (VH) coding segment, directly adjacent to the
      recombination signal sequence (RSS), placing the RSS in a position accessible to
      the recombination activating gene (RAG) recombinase. These changes result in
      establishment of a specific chromatin organization at the RSS that facilitates
      accessibility of the genomic DNA for the RAG recombinase. In contrast, in mouse
      embryonic fibroblasts the coding segment is depleted of nucleosomes, which
      instead cover the RSS, thereby rendering it inaccessible. Pro-T cells exhibit a
      pattern intermediate between pro-B cells and mouse embryonic fibroblasts. We also
      find large-scale variations of nucleosome density over hundreds of kilobases,
      delineating chromosomal domains within IgH, in a cell type-dependent manner.
      These findings suggest that developmentally regulated changes in nucleosome
      location and occupancy, in addition to the known chromatin modifications, play a
      fundamental role in regulating V(D)J recombination. Nucleosome positioning-which
      has previously been observed to vary locally at individual enhancers and
      promoters-may be a more general mechanism by which cells can regulate the
      accessibility of the genome during development, at scales ranging from several
      hundred base pairs to many kilobases.

PMID- 27698126
TI  - Democratic and Republican physicians provide different care on politicized health
      issues.
AB  - Physicians frequently interact with patients about politically salient health
      issues, such as drug use, firearm safety, and sexual behavior. We investigate
      whether physicians' own political views affect their treatment decisions on these
      issues. We linked the records of over 20,000 primary care physicians in 29 US
      states to a voter registration database, obtaining the physicians' political
      party affiliations. We then surveyed a sample of Democratic and Republican
      primary care physicians. Respondents evaluated nine patient vignettes, three of
      which addressed especially politicized health issues (marijuana, abortion, and
      firearm storage). Physicians rated the seriousness of the issue presented in each
      vignette and their likelihood of engaging in specific management options. On the
      politicized health issues-and only on such issues-Democratic and Republican
      physicians differed substantially in their expressed concern and their
      recommended treatment plan. We control for physician demographics (like age,
      gender, and religiosity), patient population, and geography. Physician partisan
      bias can lead to unwarranted variation in patient care. Awareness of how a
      physician's political attitudes might affect patient care is important to
      physicians and patients alike.

PMID- 27698125
TI  - Mint3 potentiates TLR3/4- and RIG-I-induced IFN-beta expression and antiviral
      immune responses.
AB  - Type I IFNs (IFN-alpha/beta) play crucial roles in the elimination of invading
      viruses. Multiple immune cells including macrophages recognize viral infection
      through a variety of pattern recognition receptors, such as Toll-like receptors
      (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors, and initiate
      type I IFN secretion and subsequent antiviral immune responses. However, the
      mechanisms by which host immune cells can produce adequate amounts of type I IFNs
      and then eliminate viruses effectively remain to be further elucidated. In the
      present study, we show that munc18-1-interacting protein 3 (Mint3) expression can
      be markedly induced during viral infection in macrophages. Mint3 enhances TLR3/4-
      and RIG-I-induced IRF3 activation and IFN-beta production by promoting K63-linked
      polyubiquitination of TNF receptor-associated factor 3 (TRAF3). Consistently,
      Mint3 deficiency greatly attenuated antiviral immune responses and increased
      viral replication. Therefore, we have identified Mint3 as a physiological
      positive regulator of TLR3/4 and RIG-I-induced IFN-beta production and have
      outlined a feedback mechanism for the control of antiviral immune responses.

PMID- 27698127
TI  - Environmental change explains cichlid adaptive radiation at Lake Malawi over the
      past 1.2 million years.
AB  - Long paleoecological records are critical for understanding evolutionary
      responses to environmental forcing and unparalleled tools for elucidating the
      mechanisms that lead to the development of regions of high biodiversity. We use a
      1.2-My record from Lake Malawi, a textbook example of biological diversification,
      to document how climate and tectonics have driven ecosystem and evolutionary
      dynamics. Before ~800 ka, Lake Malawi was much shallower than today, with higher
      frequency but much lower amplitude water-level and oxygenation changes. Since
      ~800 ka, the lake has experienced much larger environmental fluctuations, best
      explained by a punctuated, tectonically driven rise in its outlet location and
      level. Following the reorganization of the basin, a change in the pacing of
      hydroclimate variability associated with the Mid-Pleistocene Transition resulted
      in hydrologic change dominated by precession rather than the high-latitude
      teleconnections recorded elsewhere. During this time, extended, deep lake phases
      have abruptly alternated with times of extreme aridity and ecosystem variability.
      Repeated crossings of hydroclimatic thresholds within the lake system were
      critical for establishing the rhythm of diversification, hybridization, and
      extinction that dominate the modern system. The chronology of these changes
      closely matches both the timing and pattern of phylogenetic history inferred
      independently for the lake's extraordinary array of cichlid fish species,
      suggesting a direct link between environmental and evolutionary dynamics.

PMID- 27698128
TI  - Large-scale recovery of an endangered amphibian despite ongoing exposure to
      multiple stressors.
AB  - Amphibians are one of the most threatened animal groups, with 32% of species at
      risk for extinction. Given this imperiled status, is the disappearance of a large
      fraction of the Earth's amphibians inevitable, or are some declining species more
      resilient than is generally assumed? We address this question in a species that
      is emblematic of many declining amphibians, the endangered Sierra Nevada yellow
      legged frog (Rana sierrae). Based on >7,000 frog surveys conducted across
      Yosemite National Park over a 20-y period, we show that, after decades of decline
      and despite ongoing exposure to multiple stressors, including introduced fish,
      the recently emerged disease chytridiomycosis, and pesticides, R. sierrae
      abundance increased sevenfold during the study and at a rate of 11% per year.
      These increases occurred in hundreds of populations throughout Yosemite,
      providing a rare example of amphibian recovery at an ecologically relevant
      spatial scale. Results from a laboratory experiment indicate that these increases
      may be in part because of reduced frog susceptibility to chytridiomycosis. The
      disappearance of nonnative fish from numerous water bodies after cessation of
      stocking also contributed to the recovery. The large-scale increases in R.
      sierrae abundance that we document suggest that, when habitats are relatively
      intact and stressors are reduced in their importance by active management or
      species' adaptive responses, declines of some amphibians may be partially
      reversible, at least at a regional scale. Other studies conducted over similarly
      large temporal and spatial scales are critically needed to provide insight and
      generality about the reversibility of amphibian declines at a global scale.

PMID- 27698129
TI  - Negative cooperativity in the nitrogenase Fe protein electron delivery cycle.
AB  - Nitrogenase catalyzes the ATP-dependent reduction of dinitrogen (N2) to two
      ammonia (NH3) molecules through the participation of its two protein components,
      the MoFe and Fe proteins. Electron transfer (ET) from the Fe protein to the
      catalytic MoFe protein involves a series of synchronized events requiring the
      transient association of one Fe protein with each alphabeta half of the
      alpha2beta2 MoFe protein. This process is referred to as the Fe protein cycle and
      includes binding of two ATP to an Fe protein, association of an Fe protein with
      the MoFe protein, ET from the Fe protein to the MoFe protein, hydrolysis of the
      two ATP to two ADP and two Pi for each ET, Pi release, and dissociation of
      oxidized Fe protein-(ADP)2 from the MoFe protein. Because the MoFe protein
      tetramer has two separate alphabeta active units, it participates in two distinct
      Fe protein cycles. Quantitative kinetic measurements of ET, ATP hydrolysis, and
      Pi release during the presteady-state phase of electron delivery demonstrate that
      the two halves of the ternary complex between the MoFe protein and two reduced Fe
      protein-(ATP)2 do not undergo the Fe protein cycle independently. Instead, the
      data are globally fit with a two-branch negative-cooperativity kinetic model in
      which ET in one-half of the complex partially suppresses this process in the
      other. A possible mechanism for communication between the two halves of the
      nitrogenase complex is suggested by normal-mode calculations showing correlated
      and anticorrelated motions between the two halves.

PMID- 27698130
TI  - Exploring the aggregation free energy landscape of the amyloid-beta protein (1
      40).
AB  - A predictive coarse-grained protein force field [associative memory, water
      mediated, structure, and energy model for molecular dynamics (AWSEM)-MD] is used
      to study the energy landscapes and relative stabilities of amyloid-beta protein
      (1-40) in the monomer and all of its oligomeric forms up to an octamer. We find
      that an isolated monomer is mainly disordered with a short alpha-helix formed at
      the central hydrophobic core region (L17-D23). A less stable hairpin structure,
      however, becomes increasingly more stable in oligomers, where hydrogen bonds can
      form between neighboring monomers. We explore the structure and stability of both
      prefibrillar oligomers that consist of mainly antiparallel beta-sheets and
      fibrillar oligomers with only parallel beta-sheets. Prefibrillar oligomers are
      polymorphic but typically take on a cylindrin-like shape composed of mostly
      antiparallel beta-strands. At the concentration of the simulation, the
      aggregation free energy landscape is nearly downhill. We use umbrella sampling
      along a structural progress coordinate for interconversion between prefibrillar
      and fibrillar forms to identify a conversion pathway between these forms. The
      fibrillar oligomer only becomes favored over its prefibrillar counterpart in the
      pentamer where an interconversion bottleneck appears. The structural
      characterization of the pathway along with statistical mechanical perturbation
      theory allow us to evaluate the effects of concentration on the free energy
      landscape of aggregation as well as the effects of the Dutch and Arctic mutations
      associated with early onset of Alzheimer's disease.

PMID- 27698131
TI  - Lifespan adversity and later adulthood telomere length in the nationally
      representative US Health and Retirement Study.
AB  - Stress over the lifespan is thought to promote accelerated aging and early
      disease. Telomere length is a marker of cell aging that appears to be one
      mediator of this relationship. Telomere length is associated with early adversity
      and with chronic stressors in adulthood in many studies. Although cumulative
      lifespan adversity should have bigger impacts than single events, it is also
      possible that adversity in childhood has larger effects on later life health than
      adult stressors, as suggested by models of biological embedding in early life. No
      studies have examined the individual vs. cumulative effects of childhood and
      adulthood adversities on adult telomere length. Here, we examined the
      relationship between cumulative childhood and adulthood adversity, adding up a
      range of severe financial, traumatic, and social exposures, as well as comparing
      them to each other, in relation to salivary telomere length. We examined 4,598
      men and women from the US Health and Retirement Study. Single adversities tended
      to have nonsignificant relations with telomere length. In adjusted models,
      lifetime cumulative adversity predicted 6% greater odds of shorter telomere
      length. This result was mainly due to childhood adversity. In adjusted models for
      cumulative childhood adversity, the occurrence of each additional childhood event
      predicted 11% increased odds of having short telomeres. This result appeared
      mainly because of social/traumatic exposures rather than financial exposures.
      This study suggests that the shadow of childhood adversity may reach far into
      later adulthood in part through cellular aging.

PMID- 27698132
TI  - Epitope specificity plays a critical role in regulating antibody-dependent cell
      mediated cytotoxicity against influenza A virus.
AB  - The generation of strain-specific neutralizing antibodies against influenza A
      virus is known to confer potent protection against homologous infections. The
      majority of these antibodies bind to the hemagglutinin (HA) head domain and
      function by blocking the receptor binding site, preventing infection of host
      cells. Recently, elicitation of broadly neutralizing antibodies which target the
      conserved HA stalk domain has become a promising "universal" influenza virus
      vaccine strategy. The ability of these antibodies to elicit Fc-dependent effector
      functions has emerged as an important mechanism through which protection is
      achieved in vivo. However, the way in which Fc-dependent effector functions are
      regulated by polyclonal influenza virus-binding antibody mixtures in vivo has
      never been defined. Here, we demonstrate that interactions among viral
      glycoprotein-binding antibodies of varying specificities regulate the magnitude
      of antibody-dependent cell-mediated cytotoxicity induction. We show that the
      mechanism responsible for this phenotype relies upon competition for binding to
      HA on the surface of infected cells and virus particles. Nonneutralizing
      antibodies were poor inducers and did not inhibit antibody-dependent cell
      mediated cytotoxicity. Interestingly, anti-neuraminidase antibodies weakly
      induced antibody-dependent cell-mediated cytotoxicity and enhanced induction in
      the presence of HA stalk-binding antibodies in an additive manner. Our data
      demonstrate that antibody specificity plays an important role in the regulation
      of ADCC, and that cross-talk among antibodies of varying specificities determines
      the magnitude of Fc receptor-mediated effector functions.

PMID- 27698135
TI  - Genomic charting of ribosomally synthesized natural product chemical space
      facilitates targeted mining.
AB  - Microbial natural products are an evolved resource of bioactive small molecules,
      which form the foundation of many modern therapeutic regimes. Ribosomally
      synthesized and posttranslationally modified peptides (RiPPs) represent a class
      of natural products which have attracted extensive interest for their diverse
      chemical structures and potent biological activities. Genome sequencing has
      revealed that the vast majority of genetically encoded natural products remain
      unknown. Many bioinformatic resources have therefore been developed to predict
      the chemical structures of natural products, particularly nonribosomal peptides
      and polyketides, from sequence data. However, the diversity and complexity of
      RiPPs have challenged systematic investigation of RiPP diversity, and
      consequently the vast majority of genetically encoded RiPPs remain chemical "dark
      matter." Here, we introduce an algorithm to catalog RiPP biosynthetic gene
      clusters and chart genetically encoded RiPP chemical space. A global analysis of
      65,421 prokaryotic genomes revealed 30,261 RiPP clusters, encoding 2,231 unique
      products. We further leverage the structure predictions generated by our
      algorithm to facilitate the genome-guided discovery of a molecule from a rare
      family of RiPPs. Our results provide the systematic investigation of RiPP genetic
      and chemical space, revealing the widespread distribution of RiPP biosynthesis
      throughout the prokaryotic tree of life, and provide a platform for the targeted
      discovery of RiPPs based on genome sequencing.

PMID- 27698136
TI  - Breaking the symmetry of a viral capsid.

PMID- 27698133
TI  - Epstein-Barr virus microRNAs reduce immune surveillance by virus-specific CD8+ T
      cells.
AB  - Infection with Epstein-Barr virus (EBV) affects most humans worldwide and
      persists life-long in the presence of robust virus-specific T-cell responses. In
      both immunocompromised and some immunocompetent people, EBV causes several
      cancers and lymphoproliferative diseases. EBV transforms B cells in vitro and
      encodes at least 44 microRNAs (miRNAs), most of which are expressed in EBV
      transformed B cells, but their functions are largely unknown. Recently, we showed
      that EBV miRNAs inhibit CD4+ T-cell responses to infected B cells by targeting IL
      12, MHC class II, and lysosomal proteases. Here we investigated whether EBV
      miRNAs also counteract surveillance by CD8+ T cells. We have found that EBV
      miRNAs strongly inhibit recognition and killing of infected B cells by EBV
      specific CD8+ T cells through multiple mechanisms. EBV miRNAs directly target the
      peptide transporter subunit TAP2 and reduce levels of the TAP1 subunit, MHC class
      I molecules, and EBNA1, a protein expressed in most forms of EBV latency and a
      target of EBV-specific CD8+ T cells. Moreover, miRNA-mediated down-regulation of
      the cytokine IL-12 decreases the recognition of infected cells by EBV-specific
      CD8+ T cells. Thus, EBV miRNAs use multiple, distinct pathways, allowing the
      virus to evade surveillance not only by CD4+ but also by antiviral CD8+ T cells.

PMID- 27698137
TI  - System crash as dynamics of complex networks.
AB  - Complex systems, from animal herds to human nations, sometimes crash drastically.
      Although the growth and evolution of systems have been extensively studied, our
      understanding of how systems crash is still limited. It remains rather puzzling
      why some systems, appearing to be doomed to fail, manage to survive for a long
      time whereas some other systems, which seem to be too big or too strong to fail,
      crash rapidly. In this contribution, we propose a network-based system dynamics
      model, where individual actions based on the local information accessible in
      their respective system structures may lead to the "peculiar" dynamics of system
      crash mentioned above. Extensive simulations are carried out on synthetic and
      real-life networks, which further reveal the interesting system evolution leading
      to the final crash. Applications and possible extensions of the proposed model
      are discussed.

PMID- 27698134
TI  - Cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells
      (MSCs).
AB  - Patients with breast cancer often develop malignant regrowth of residual drug
      resistant dormant tumor cells years after primary treatment, a process defined as
      cancer relapse. Deciphering the causal basis of tumor dormancy therefore has
      obvious therapeutic significance. Because cancer cell behavior is strongly
      influenced by stromal cells, particularly the mesenchymal stem/stromal cells
      (MSCs) that are actively recruited into tumor-associated stroma, we assessed the
      impact of MSCs on breast cancer cell (BCC) dormancy. Using 3D cocultures to mimic
      the cellular interactions of an emerging tumor niche, we observed that MSCs
      sequentially surrounded the BCCs, promoted formation of cancer spheroids, and
      then were internalized/degraded through a process resembling the well-documented
      yet ill-defined clinical phenomenon of cancer cell cannibalism. This suspected
      feeding behavior was less appreciable in the presence of a rho kinase inhibitor
      and in 2D monolayer cocultures. Notably, cannibalism of MSCs enhanced survival of
      BCCs deprived of nutrients but suppressed their tumorigenicity, together
      suggesting the cancer cells entered dormancy. Transcriptome profiles revealed
      that the resulting BCCs acquired a unique molecular signature enriched in
      prosurvival factors and tumor suppressors, as well as inflammatory mediators that
      demarcate the secretome of senescent cells, also referred to as the senescence
      associated secretory phenotype. Overall, our results provide intriguing evidence
      that cancer cells under duress enter dormancy after cannibalizing MSCs.
      Importantly, our practical 3D coculture model could provide a valuable tool to
      understand the antitumor activity of MSCs and cell cannibalism further, and
      therefore open new therapeutic avenues for the prevention of cancer recurrence.

PMID- 27698139
TI  - QnAs with Alan G. Hinnebusch.

PMID- 27698138
TI  - Mushroom spine dynamics in medium spiny neurons of dorsal striatum associated
      with memory of moderate and intense training.
AB  - A growing body of evidence indicates that treatments that typically impair memory
      consolidation become ineffective when animals are given intense training. This
      effect has been obtained by treatments interfering with the neural activity of
      several brain structures, including the dorsal striatum. The mechanisms that
      mediate this phenomenon are unknown. One possibility is that intense training
      promotes the transfer of information derived from the enhanced training to a
      wider neuronal network. We now report that inhibitory avoidance (IA) induces
      mushroom spinogenesis in the medium spiny neurons (MSNs) of the dorsal striatum
      in rats, which is dependent upon the intensity of the foot-shock used for
      training; that is, the effect is seen only when high-intensity foot-shock is used
      in training. We also found that the relative density of thin spines was reduced.
      These changes were evident at 6 h after training and persisted for at least 24 h
      afterward. Importantly, foot-shock alone did not increase spinogenesis. Spine
      density in MSNs in the accumbens was also increased, but the increase did not
      correlate with the associative process involved in IA; rather, it resulted from
      the administration of the aversive stimulation alone. These findings suggest that
      mushroom spines of MSNs of the dorsal striatum receive afferent information that
      is involved in the integrative activity necessary for memory consolidation, and
      that intense training facilitates transfer of information from the dorsal
      striatum to other brain regions through augmented spinogenesis.

PMID- 27698140
TI  - Spectroscopic elucidation of energy transfer in hybrid inorganic-biological
      organisms for solar-to-chemical production.
AB  - The rise of inorganic-biological hybrid organisms for solar-to-chemical
      production has spurred mechanistic investigations into the dynamics of the biotic
      abiotic interface to drive the development of next-generation systems. The model
      system, Moorella thermoacetica-cadmium sulfide (CdS), combines an inorganic
      semiconductor nanoparticle light harvester with an acetogenic bacterium to drive
      the photosynthetic reduction of CO2 to acetic acid with high efficiency. In this
      work, we report insights into this unique electrotrophic behavior and propose a
      charge-transfer mechanism from CdS to M. thermoacetica Transient absorption (TA)
      spectroscopy revealed that photoexcited electron transfer rates increase with
      increasing hydrogenase (H2ase) enzyme activity. On the same time scale as the TA
      spectroscopy, time-resolved infrared (TRIR) spectroscopy showed spectral changes
      in the 1,700-1,900-cm-1 spectral region. The quantum efficiency of this system
      for photosynthetic acetic acid generation also increased with increasing H2ase
      activity and shorter carrier lifetimes when averaged over the first 24 h of
      photosynthesis. However, within the initial 3 h of photosynthesis, the rate
      followed an opposite trend: The bacteria with the lowest H2ase activity
      photosynthesized acetic acid the fastest. These results suggest a two-pathway
      mechanism: a high quantum efficiency charge-transfer pathway to H2ase generating
      H2 as a molecular intermediate that dominates at long time scales (24 h), and a
      direct energy-transducing enzymatic pathway responsible for acetic acid
      production at short time scales (3 h). This work represents a promising platform
      to utilize conventional spectroscopic methodology to extract insights from more
      complex biotic-abiotic hybrid systems.

PMID- 27698141
TI  - Aging, memory, and nonhierarchical energy landscape of spin jam.
AB  - The notion of complex energy landscape underpins the intriguing dynamical
      behaviors in many complex systems ranging from polymers, to brain activity, to
      social networks and glass transitions. The spin glass state found in dilute
      magnetic alloys has been an exceptionally convenient laboratory frame for
      studying complex dynamics resulting from a hierarchical energy landscape with
      rugged funnels. Here, we show, by a bulk susceptibility and Monte Carlo
      simulation study, that densely populated frustrated magnets in a spin jam state
      exhibit much weaker memory effects than spin glasses, and the characteristic
      properties can be reproduced by a nonhierarchical landscape with a wide and
      nearly flat but rough bottom. Our results illustrate that the memory effects can
      be used to probe different slow dynamics of glassy materials, hence opening a
      window to explore their distinct energy landscapes.

PMID- 27698142
TI  - Enhancer priming by H3K4 methyltransferase MLL4 controls cell fate transition.
AB  - Transcriptional enhancers control cell-type-specific gene expression. Primed
      enhancers are marked by histone H3 lysine 4 (H3K4) mono/di-methylation
      (H3K4me1/2). Active enhancers are further marked by H3K27 acetylation (H3K27ac).
      Mixed-lineage leukemia 4 (MLL4/KMT2D) is a major enhancer H3K4me1/2
      methyltransferase with functional redundancy with MLL3 (KMT2C). However, its role
      in cell fate maintenance and transition is poorly understood. Here, we show in
      mouse embryonic stem cells (ESCs) that MLL4 associates with, but is surprisingly
      dispensable for the maintenance of, active enhancers of cell-identity genes. As a
      result, MLL4 is dispensable for cell-identity gene expression and self-renewal in
      ESCs. In contrast, MLL4 is required for enhancer-binding of H3K27
      acetyltransferase p300, enhancer activation, and induction of cell-identity genes
      during ESC differentiation. MLL4 protein, rather than MLL4-mediated H3K4
      methylation, controls p300 recruitment to enhancers. We also show that, in
      somatic cells, MLL4 is dispensable for maintaining cell identity but essential
      for reprogramming into induced pluripotent stem cells. These results indicate
      that, although enhancer priming by MLL4 is dispensable for cell-identity
      maintenance, it controls cell fate transition by orchestrating p300-mediated
      enhancer activation.

PMID- 27698143
TI  - Simplified derivation of the gravitational wave stress tensor from the linearized
      Einstein field equations.
AB  - A conserved stress energy tensor for weak field gravitational waves propagating
      in vacuum is derived directly from the linearized general relativistic wave
      equation alone, for an arbitrary gauge. In any harmonic gauge, the form of the
      tensor leads directly to the classical expression for the outgoing wave energy.
      The method described here, however, is a much simpler, shorter, and more
      physically motivated approach than is the customary procedure, which involves a
      lengthy and cumbersome second-order (in wave-amplitude) calculation starting with
      the Einstein tensor. Our method has the added advantage of exhibiting the direct
      coupling between the outgoing wave energy flux and the work done by the
      gravitational field on the sources. For nonharmonic gauges, the directly derived
      wave stress tensor has an apparent index asymmetry. This coordinate artifact may
      be straightforwardly removed, and the symmetrized (still gauge-invariant) tensor
      then takes on its widely used form. Angular momentum conservation follows
      immediately. For any harmonic gauge, however, the stress tensor found is
      manifestly symmetric from the start, and its derivation depends, in its entirety,
      on the structure of the linearized wave equation.

PMID- 27698144
TI  - Disorder drives cooperative folding in a multidomain protein.
AB  - Many human proteins contain intrinsically disordered regions, and disorder in
      these proteins can be fundamental to their function-for example, facilitating
      transient but specific binding, promoting allostery, or allowing efficient
      posttranslational modification. SasG, a multidomain protein implicated in host
      colonization and biofilm formation in Staphylococcus aureus, provides another
      example of how disorder can play an important role. Approximately one-half of the
      domains in the extracellular repetitive region of SasG are intrinsically unfolded
      in isolation, but these E domains fold in the context of their neighboring folded
      G5 domains. We have previously shown that the intrinsic disorder of the E domains
      mediates long-range cooperativity between nonneighboring G5 domains, allowing
      SasG to form a long, rod-like, mechanically strong structure. Here, we show that
      the disorder of the E domains coupled with the remarkable stability of the
      interdomain interface result in cooperative folding kinetics across long
      distances. Formation of a small structural nucleus at one end of the molecule
      results in rapid structure formation over a distance of 10 nm, which is likely to
      be important for the maintenance of the structural integrity of SasG. Moreover,
      if this normal folding nucleus is disrupted by mutation, the interdomain
      interface is sufficiently stable to drive the folding of adjacent E and G5
      domains along a parallel folding pathway, thus maintaining cooperative folding.

PMID- 27698145
TI  - Genetic mapping of male pheromone response in the European corn borer identifies
      candidate genes regulating neurogenesis.
AB  - The sexual pheromone communication system of moths is a model system for studies
      of the evolution of reproductive isolation. Females emit a blend of volatile
      components that males detect at a distance. Species differences in female
      pheromone composition and male response directly reinforce reproductive isolation
      in nature, because even slight variations in the species-specific pheromone blend
      are usually rejected by the male. The mechanisms by which a new pheromone signal
      response system could evolve are enigmatic, because any deviation from the
      optimally attractive blend should be selected against. Here we investigate the
      genetic mechanisms enabling a switch in male response. We used a quantitative
      trait locus-mapping approach to identify the genetic basis of male response in
      the two pheromone races of the European corn borer, Ostrinia nubilalis Male
      response to a 99:1 vs. a 3:97 ratio of the E and Z isomers of the female
      pheromone is governed by a single, sex-linked locus. We found that the
      chromosomal region most tightly linked to this locus contains genes involved in
      neurogenesis but, in accordance with an earlier study, does not contain the
      odorant receptors expressed in the male antenna that detect the pheromone. This
      finding implies that differences in the development of neuronal pathways
      conveying information from the antenna, not differences in pheromone detection by
      the odorant receptors, are primarily responsible for the behavioral response
      differences among the males in this system. Comparison with other moth species
      reveals a previously unexplored mechanism by which male pheromone response can
      change in evolution.

PMID- 27698146
TI  - A competing hydrophobic tug on L596 to the membrane core unlatches S4-S5 linker
      elbow from TRP helix and allows TRPV4 channel to open.
AB  - We have some generalized physical understanding of how ion channels interact with
      surrounding lipids but few detailed descriptions on how interactions of
      particular amino acids with contacting lipids may regulate gating. Here we
      discovered a structure-specific interaction between an amino acid and inner
      leaflet lipid that governs the gating transformations of TRPV4 (transient
      receptor potential vanilloid type 4). Many cation channels use a S4-S5 linker to
      transmit stimuli to the gate. At the start of TRPV4's linker helix is leucine
      596. A hydrogen bond between the indole of W733 of the TRP helix and the backbone
      oxygen of L596 secures the helix/linker contact, which acts as a latch
      maintaining channel closure. The modeled side chain of L596 interacts with the
      inner lipid leaflet near the polar-nonpolar interface in our model-an interaction
      that we explored by mutagenesis. We examined the outward currents of TRPV4
      expressing Xenopus oocyte upon depolarizations as well as phenotypes of
      expressing yeast cells. Making this residue less hydrophobic (L596A/G/W/Q/K)
      reduces open probability [Po; loss-of-function (LOF)], likely due to altered
      interactions at the polar-nonpolar interface. L596I raises Po [gain-of-function
      (GOF)], apparently by placing its methyl group further inward and receiving
      stronger water repulsion. Molecular dynamics simulations showed that the distance
      between the levels of alpha-carbons of H-bonded residues L596 and W733 is
      shortened in the LOFs and lengthened in the GOFs, strengthening or weakening the
      linker/TRP helix latch, respectively. These results highlight that L596 lipid
      attraction counteracts the latch bond in a tug-of-war to tune the Po of TRPV4.

PMID- 27698147
TI  - Designing steep, sharp patterns on uniformly ion-bombarded surfaces.
AB  - We propose and experimentally test a method to fabricate patterns of steep, sharp
      features on surfaces, by exploiting the nonlinear dynamics of uniformly ion
      bombarded surfaces. We show via theory, simulation, and experiment that the
      steepest parts of the surface evolve as one-dimensional curves that move in the
      normal direction at constant velocity. The curves are a special solution to the
      nonlinear equations that arises spontaneously whenever the initial patterning on
      the surface contains slopes larger than a critical value; mathematically they are
      traveling waves (shocks) that have the special property of being
      undercompressive. We derive the evolution equation for the curves by considering
      long-wavelength perturbations to the one-dimensional traveling wave, using the
      unusual boundary conditions required for an undercompressive shock, and we show
      this equation accurately describes the evolution of shapes on surfaces, both in
      simulations and in experiments. Because evolving a collection of one-dimensional
      curves is fast, this equation gives a computationally efficient and intuitive
      method for solving the inverse problem of finding the initial surface so the
      evolution leads to a desired target pattern. We illustrate this method by solving
      for the initial surface that will produce a lattice of diamonds connected by
      steep, sharp ridges, and we experimentally demonstrate the evolution of the
      initial surface into the target pattern.

PMID- 27698150
TI  - Trend of homicide-suicide in Kanagawa Prefecture (Japan): Comparison with western
      countries.
AB  - We examined 169 deceased persons and 76 homicide-suicide cases reported in
      Japan's Kanagawa Prefecture from 1999 to 2011. The relationships between homicide
      suicide perpetrators and homicide victims; the numbers of victims; their age,
      sex, causes and places of death; motivation; and the presence or absence of a
      suicide note were extracted and examined. The relationship between homicide
      suicide perpetrators and homicide victims was examined based on findings from the
      following: 24 married couples (31%), 22 parents and children aged >=18 years
      (29%), 19 parents and children aged <=17 years (25%), seven families (9%), two
      couples (3%) and two miscellaneous relationships (3%). The perpetrators comprised
      39 men and 40 women, with a mean age of 51.6 years. The victims comprised 39 men
      and 51 women, with a mean age of 35.4 years. In our study, approximately half of
      the perpetrators were female, which differed greatly from the reports from
      Western countries, where most perpetrators were male. Homicide-suicides among
      married couples accounted for a higher proportion of overall homicide-suicide
      deaths in Western countries. In Japan, homicide-suicide occurred more frequently
      with parents and children. Cases in which a mother committed suicide after having
      killed her young children accounted for a high proportion of these deaths.
      Because these events occur so frequently in Japan, we recommend making particular
      efforts to reduce homicide-suicides among mothers and children.

PMID- 27698148
TI  - Multiscale implementation of infinite-swap replica exchange molecular dynamics.
AB  - Replica exchange molecular dynamics (REMD) is a popular method to accelerate
      conformational sampling of complex molecular systems. The idea is to run several
      replicas of the system in parallel at different temperatures that are swapped
      periodically. These swaps are typically attempted every few MD steps and accepted
      or rejected according to a Metropolis-Hastings criterion. This guarantees that
      the joint distribution of the composite system of replicas is the normalized sum
      of the symmetrized product of the canonical distributions of these replicas at
      the different temperatures. Here we propose a different implementation of REMD in
      which (i) the swaps obey a continuous-time Markov jump process implemented via
      Gillespie's stochastic simulation algorithm (SSA), which also samples exactly the
      aforementioned joint distribution and has the advantage of being rejection free,
      and (ii) this REMD-SSA is combined with the heterogeneous multiscale method to
      accelerate the rate of the swaps and reach the so-called infinite-swap limit that
      is known to optimize sampling efficiency. The method is easy to implement and can
      be trivially parallelized. Here we illustrate its accuracy and efficiency on the
      examples of alanine dipeptide in vacuum and C-terminal beta-hairpin of protein G
      in explicit solvent. In this latter example, our results indicate that the
      landscape of the protein is a triple funnel with two folded structures and one
      misfolded structure that are stabilized by H-bonds.

PMID- 27698149
TI  - Respiratory and Enteric Virus Detection in Children.
AB  - The majority of children with febrile seizures have viral infections and viruses
      were detected in 22% to 63% of children in published studies. Using molecular
      methods, viruses were also detected in asymptomatic persons. A prospective study
      was conducted to detect respiratory and enteric viruses in 192 children with
      febrile seizures and compare the detection rates to those found in 156 healthy
      age-matched controls. A respiratory or enteric virus was detected in 72.9% of
      children with febrile seizures and in 51.4% of healthy controls. The viruses most
      strongly associated with febrile seizures were influenza, respiratory syncytial
      virus, parainfluenza, human coronavirus, and rotavirus. Compared to healthy
      controls, the age-adjusted odds ratios for nasopharynx virus positivity in
      febrile seizure patients were 79.4, 2.8, 7.2, and 4.9 for influenza virus,
      parainfluenza virus, respiratory syncytial virus, and human coronavirus,
      respectively, and 22.0 for rotavirus in stool. The detected virus did not
      influence clinical features of febrile seizure.

PMID- 27698151
TI  - Bilateral injury of the superior longitudinal fasciculus in a patient with Balint
      syndrome.

PMID- 27698152
TI  - A reversible severe gait disorder.

PMID- 27698153
TI  - Long-term use of daily sumatriptan injections in severe drug-resistant chronic
      cluster headache.

PMID- 27698155
TI  - Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the
      randomized TEMSO study.

PMID- 27698157
TI  - Right Brain: Concussion (film): Review and historical context.

PMID- 27698154
TI  - Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by
      disease stage.

PMID- 27698156
TI  - Clinical Reasoning: A 2-year-old child with acute flaccid paralysis.

PMID- 27698158
TI  - Teaching NeuroImages: Neuroradiologic evolution of Leigh disease.

PMID- 27698159
TI  - Teaching NeuroImages: Morgagni-Stewart-Morel: A metabolic craniopathy.

PMID- 27698162
TI  - Neoplasia in 125 donkeys (Equus asinus): literature review and a survey of five
      veterinary schools in the United States and Canada.
AB  - A diagnosis of neoplasia was noted in 125 of 357 donkeys (35%) in our review of
      medical records from 5 veterinary schools in the United States and Canada. Equine
      sarcoid was the most common tumor in our study, accounting for 72% of all tumors
      and 82% of cutaneous tumors. Soft-tissue sarcomas were the second most common
      skin tumors. All other types of neoplasia were rare. Important differences in the
      occurrence of neoplasia in donkeys compared to horses included the rarity or
      absence of squamous cell carcinoma in any organ system and gray horse melanoma.
      Lymphosarcoma, the most common malignant tumor in horses, appears to be very rare
      in donkeys. We report several tumors in donkeys including melanocytoma,
      peripheral nerve sheath tumor, and gastrointestinal stromal tumor. Our data
      demonstrate commonalities as well as differences in neoplastic diseases of
      donkeys and horses. Understanding differences in carcinogenesis among these 2
      closely related species can inform researchers pursuing pathogenic mechanisms of
      equine disease and inform veterinary diagnosticians regarding tumor prevalence.

PMID- 27698163
TI  - Tissue localization, shedding, virus carriage, antibody response, and aerosol
      transmission of Porcine epidemic diarrhea virus following inoculation of 4-week
      old feeder pigs.
AB  - We determined tissue localization, shedding patterns, virus carriage, antibody
      response, and aerosol transmission of Porcine epidemic diarrhea virus (PEDV)
      following inoculation of 4-week-old feeder pigs. Thirty-three pigs were randomly
      assigned to 1 of 3 groups for the 42-day study: inoculated (group A; n = 23),
      contact transmission (group B; n = 5), and aerosol transmission (group C; n = 5).
      Contact transmission occurred rapidly to group B pigs whereas productive aerosol
      transmission failed to occur to group C pigs. Emesis was the first clinical sign
      noted at 3 days postinoculation (dpi) followed by mild to moderate diarrhea
      lasting 5 more days. Real-time PCR detected PEDV in fecal and nasal swabs, oral
      fluids, serum, and gastrointestinal and lymphoid tissues. Shedding occurred
      primarily during the first 2 weeks postinoculation, peaking at 5-6 dpi; however,
      some pigs had PEDV nucleic acid detected in swabs collected at 21 and 28 dpi.
      Antibody titers were measurable between 14 and 42 dpi. Although feces and
      intestines collected at 42 dpi were PEDV negative by PCR and
      immunohistochemistry, respectively, small intestines from 70% of group A pigs
      were PCR positive. Although disease was relatively mild and transient in this age
      group, the results demonstrate that 4-week-old pigs are productively infected and
      can sustain virus replication for several weeks. Long-term shedding of PEDV in
      subclinically affected pigs should be considered an important source for PEDV
      transmission.

PMID- 27698165
TI  - Concurrent spindle-cell thymoma and thymic cysts in a Barbary sheep (Ammotragus
      lervia): case report and review of the literature.
AB  - An ~21-year-old female Barbary sheep (Ammotragus lervia) died spontaneously
      following a lengthy episode of difficulty in walking. An ~6 * 3 * 3 cm,
      unilocular cystic growth was found in the cranioventral thorax. The fibrotic
      cystic wall, lined by a single layer of flattened to cuboidal epithelial cells,
      was invaginated and partially encircled solid masses of fusiform neoplastic cells
      with multiple intratumoral cystic structures. The fusiform neoplastic cells were
      intensely positive for cytokeratin (CK) and partially positive for alpha-smooth
      muscle actin and vimentin, but negative for thyroid transcription factor-1 (TTF
      1) and neuron-specific enolase (NSE). The intratumoral cysts were lined by CK
      positive but TTF-1- negative, NSE-negative, flattened, cuboidal to columnar
      epithelial cells, suggestive of cystically dilated medullary duct epithelium
      derived structures. Based on the location and histopathologic findings of the
      growth, concurrent spindle-cell thymoma and thymic cysts was diagnosed. We also
      discuss the correlation between thymic cysts and thymoma and review the
      literature of thymomas in ovine and wildlife species.

PMID- 27698164
TI  - Isolation and identification of Caviibacter abscessus from cervical abscesses in
      a series of pet guinea pigs (Cavia porcellus).
AB  - An organism reported in the early literature to be a rare cause of cervical
      lymphadenitis in guinea pigs, Streptobacillus moniliformis, has been reclassified
      as Caviibacter abscessus We describe a series of sequential cases of abscesses in
      guinea pigs that were presented to our clinic from which the only agent isolated
      was a unique, serum-requiring bacterium. Discrete colonies were not detected in
      6.5% CO2 or anaerobically on routine primary isolation media containing up to 5%
      whole sheep blood, with and without cysteine, vitamin K, and hemin
      supplementation after 7 days of incubation at 37 degrees C. Based on subsequently
      determined growth requirements, the organisms were best described as serum
      requiring, aerotolerant anaerobes. Colonies were detectable within 24 h at 37
      degrees C in an anaerobic atmosphere on a mycoplasma agar-based medium containing
      10% pig serum and reached 3 mm in diameter within 3-5 days. Microscopic
      appearance consisted of small gram-negative rods and coccobacilli with occasional
      filaments. However, in direct smears from clinical specimens and from weak or
      dysgonic growth on plates incubated under suboptimal growth conditions (e.g., in
      6.5% CO2), irregular rods with occasional small bulbous forms or numerous long
      wavy filaments were observed. All of the isolates generated unique spectral
      profiles similar to that of C. abscessus when examined by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. Phylogenetic analysis of
      partial 16S rRNA gene sequences showed that the isolates were identical to each
      other and shared 99.9% sequence identity with C. abscessus.

PMID- 27698166
TI  - Validation of three automated assays for total antioxidant capacity determination
      in canine serum samples.
AB  - We performed analytical validation of 3 automated assays of the total antioxidant
      capacity (TAC) in canine serum and evaluated their use in dogs with inflammatory
      bowel disease. The assays were based on the generation of a 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonic acid) radical cation (ABTS*+) in aqueous media,
      which produces a blue-green color. The antioxidants present in the sample remove
      the chromogen in proportion to their concentrations. The assays differed mainly
      in the way in which this radical was produced. All 3 assays produced acceptable
      results in the analytical validation. However, only 2 of the assays were capable
      of detecting significantly different TAC values in healthy and diseased animals.

PMID- 27698167
TI  - Hernia of the swim bladder (aerocystocele) with concurrent mycotic granulomatous
      inflammation and swim bladder carcinoma in a wild mullet (Mugil cephalus).
AB  - We describe a hernia of the swim bladder, with a concurrent mycotic granulomatous
      inflammation, and carcinoma of the swim bladder in a wild mullet (Mugil cephalus)
      referred for an exophytic dorsal mass. Grossly, the mass was white, soft, and
      composed of multiple cystic gas-containing chambers connected by a funnel-shaped
      tissue segment to the coelomic swim bladder. Histologically, the mass was
      characterized by cysts of variable size, multifocally contiguous with the
      subepithelial rete mirabile, supported by abundant fibrous tissue. The skin
      covering the herniated swim bladder was focally ulcerated and replaced by
      abundant granulation tissue in which multiple scattered granulomas centered on
      pigmented fungal hyphae were observed. These granulomas were also seen in the
      remaining coelomic portion of the swim bladder as well as in the spleen,
      perivisceral pancreas, and peritoneal adipose tissue; the fungus was molecularly
      identified as Cladosporium spp. Focally, arising from the herniated swim bladder
      epithelium, an unencapsulated poorly demarcated, moderately cellular neoplasm,
      composed of islands, lobules, and acini of neoplastic epithelium, was found.

PMID- 27698168
TI  - Evaluation of supervised machine-learning algorithms to distinguish between
      inflammatory bowel disease and alimentary lymphoma in cats.
AB  - Inflammatory bowel disease (IBD) and alimentary lymphoma (ALA) are common
      gastrointestinal diseases in cats. The very similar clinical signs and
      histopathologic features of these diseases make the distinction between them
      diagnostically challenging. We tested the use of supervised machine-learning
      algorithms to differentiate between the 2 diseases using data generated from
      noninvasive diagnostic tests. Three prediction models were developed using 3
      machine-learning algorithms: naive Bayes, decision trees, and artificial neural
      networks. The models were trained and tested on data from complete blood count
      (CBC) and serum chemistry (SC) results for the following 3 groups of client-owned
      cats: normal, inflammatory bowel disease (IBD), or alimentary lymphoma (ALA).
      Naive Bayes and artificial neural networks achieved higher classification
      accuracy (sensitivities of 70.8% and 69.2%, respectively) than the decision tree
      algorithm (63%, p < 0.0001). The areas under the receiver-operating
      characteristic curve for classifying cases into the 3 categories was 83% by naive
      Bayes, 79% by decision tree, and 82% by artificial neural networks. Prediction
      models using machine learning provided a method for distinguishing between ALA
      IBD, ALA-normal, and IBD-normal. The naive Bayes and artificial neural networks
      classifiers used 10 and 4 of the CBC and SC variables, respectively, to
      outperform the C4.5 decision tree, which used 5 CBC and SC variables in
      classifying cats into the 3 classes. These models can provide another noninvasive
      diagnostic tool to assist clinicians with differentiating between IBD and ALA,
      and between diseased and nondiseased cats.

PMID- 27698169
TI  - Evaluation of a PCR assay on overgrown environmental samples cultured for
      Mycobacterium avium subsp. paratuberculosis.
AB  - Culture of Mycobacterium avium subsp. paratuberculosis (MAP) is the definitive
      antemortem test method for paratuberculosis. Microbial overgrowth is a challenge
      for MAP culture, as it complicates, delays, and increases the cost of the
      process. Additionally, herd status determination is impeded when noninterpretable
      (NI) results are obtained. The performance of PCR is comparable to fecal culture,
      thus it may be a complementary detection tool to classify NI samples. Our study
      aimed to determine if MAP DNA can be identified by PCR performed on NI
      environmental samples and to evaluate the performance of PCR before and after the
      culture of these samples in liquid media. A total of 154 environmental samples
      (62 NI, 62 negative, and 30 positive) were analyzed by PCR before being incubated
      in an automated system. Growth was confirmed by acid-fast bacilli stain and then
      the same PCR method was again applied on incubated samples, regardless of culture
      and stain results. Change in MAP DNA after incubation was assessed by converting
      the PCR quantification cycle (Cq) values into fold change using the 2-DeltaCq
      method (DeltaCq = Cq after culture - Cq before culture). A total of 1.6%
      (standard error [SE] = 1.6) of the NI environmental samples had detectable MAP
      DNA. The PCR had a significantly better performance when applied after culture
      than before culture (p = 0.004). After culture, a 66-fold change (SE = 17.1) in
      MAP DNA was observed on average. Performing a PCR on NI samples improves MAP
      culturing. The PCR method used in our study is a reliable and consistent method
      to classify NI environmental samples.

PMID- 27698170
TI  - Snake fungal disease caused by Ophidiomyces ophiodiicola in a free-ranging mud
      snake (Farancia abacura).
AB  - Snake fungal disease is an emerging infectious disease caused by the fungus
      Ophidiomyces ophiodiicola leading to severe dermatitis and facial disfiguration
      in numerous free-ranging and captive snakes. A free-ranging mud snake (Farancia
      abacura) from Bulloch County, Georgia, was presented for autopsy because of
      facial swelling and emaciation. Extensive ulceration of the skin, which was
      especially severe on the head, and retained shed were noted on external
      examination. Microscopic examination revealed severe heterophilic dermatitis with
      intralesional fungal hyphae and arthroconidia consistent with O. ophiodiicola A
      skin sample incubated on Sabouraud dextrose agar yielded a white-to-tan powdery
      fungal culture that was confirmed to be O. ophiodiicola by polymerase chain
      reaction and sequence analysis. Heavy infestation with adult tapeworms
      (Ophiotaenia faranciae) was present within the intestine. Various bacterial and
      fungal species, interpreted to either be secondary invaders or postmortem
      contaminants, were associated with oral lesions. Although the role of these other
      organisms in the overall health of this individual is not known, factors such as
      concurrent infections or immunosuppression should be considered in order to
      better understand the overall manifestation of snake fungal disease, which
      remains poorly characterized in its host range and geographic distribution.

PMID- 27698171
TI  - Mycobacterium haemophilum infection in a juvenile leatherback sea turtle
      (Dermochelys coriacea).
AB  - Mycobacteriosis is infrequently reported in free-ranging sea turtles.
      Nontuberculous Mycobacterium haemophilum was identified as the causative agent of
      disseminated mycobacteriosis in a juvenile leatherback turtle (Dermochelys
      coriacea) that was found stranded on the Atlantic coast of Florida. Disseminated
      granulomatous inflammation was identified histologically, most notably affecting
      the nervous system. Identification of mycobacterial infection was based on
      cytologic, molecular, histologic, and microbiologic methods. Among stranded sea
      turtles received for diagnostic evaluation from the Atlantic and Gulf of Mexico
      coasts of the United States between 2004 and 2015, the diagnosis of
      mycobacteriosis was overrepresented in stranded oceanic-phase juveniles compared
      with larger size classes, which suggests potential differences in susceptibility
      or exposure among different life phases in this region. We describe M.
      haemophilum in a sea turtle, which contributes to the knowledge of diseases of
      small juvenile sea turtles, an especially cryptic life phase of the leatherback
      turtle.

PMID- 27698172
TI  - Unclassified sarcomas: a study to improve classification in a cohort of Golden
      Retriever dogs.
AB  - Morphologically, canine soft-tissue sarcomas (STSs) resemble human STSs. In
      humans, proper classification of STSs is considered essential to improve insight
      in the biology of these tumors, and to optimize diagnosis and therapy. To date,
      there is a paucity of data published on the significance of detailed
      classification of STSs in the dog. We revised a cohort (n = 110) of proliferative
      lesions obtained from a study in Golden Retrievers that were considered "soft
      tissue sarcoma, not otherwise specified or of uncertain subtype" in order to
      optimize the diagnoses of these lesions. The criteria according to the veterinary
      WHO classification, recent veterinary literature, and the WHO classification for
      humans were applied. Revision was initially based on morphologic characteristics
      of hematoxylin and eosin-stained histologic sections of the neoplasms. If
      considered necessary (n = 76), additional immunohistochemistry was applied to aid
      characterization. The diagnosis of STS was confirmed in 75 neoplasms (68%). Of
      this group, diagnosis of a specific subtype of the STSs was possible in 58
      neoplasms. Seven neoplasms had morphologic characteristics that were suggestive
      for sarcoma subtypes only described in the WHO classification for humans.
      Seventeen neoplasms remained "unclassified STSs." Thirty-one lesions (28%) were
      diagnosed "neoplasm, not being STS." Four lesions (4%) were considered
      nonneoplastic. Because incorrect classification of a tumor could lead to
      inappropriate therapeutic intervention and prognostication, the results of our
      study clearly illustrate the importance of revision and further diagnosis of
      "unclassified STSs" in dogs.

PMID- 27698173
TI  - Pseudomonas aeruginosa mastitis in two goats associated with an essential oil
      based teat dip.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that has been associated with
      mastitis in dairy animals, including goats. Often, the environmental sources of
      the bacteria are water-related (such as hoses and muddy pastures). Mastitis
      attributable to P. aeruginosa was identified in 2 goats in a small herd. Efforts
      were made to identify environmental sources of the pathogen. Multiple samples
      from the goats' environment were cultured, including water from the trough,
      bedding, the hose used to wash udders, and the teat dip and teat dip containers.
      The bacterium was isolated from the teat dip and the teat dip container. The teat
      dip consisted of water, liquid soap, and several drops of essential oils
      (including tea tree, lavender, and peppermint). This case illustrates a potential
      problem that may arise as a result of the use of unconventional ingredients in
      teat dips. The use of alternative products by goat producers is likely to
      increase in the future.

PMID- 27698174
TI  - Coinfection by Cetacean morbillivirus and Aspergillus fumigatus in a juvenile
      bottlenose dolphin (Tursiops truncatus) in the Gulf of Mexico.
AB  - A recently deceased juvenile male bottlenose dolphin (Tursiops truncatus) was
      found floating in the Gulf of Mexico, off Sand Key in Clearwater, Florida. At
      autopsy, we identified pneumonia and a focus of malacia in the right cerebrum.
      Cytologic evaluation of tissue imprints from the right cerebrum revealed fungal
      hyphae. Fungal cultures of the lung and brain yielded Aspergillus fumigatus,
      which was confirmed by amplification of a portion of the fungal nuclear ribosomal
      internal transcribed spacer 2 region sequence. Microscopic pulmonary lesions of
      bronchiolar epithelial cell syncytia with intracytoplasmic and intranuclear
      inclusions within bronchiolar epithelial cells were suggestive of Cetacean
      morbillivirus (CeMV) infection. The occurrence of CeMV infection was supported by
      positive immunohistochemical staining for morbillivirus antigen. CeMV detection
      was confirmed by amplification and sequencing a portion of the morbilliviral RNA
      dependent RNA polymerase gene from lung tissue. This case provides CeMV sequence
      data available from the Gulf of Mexico and underscores the need for genomic
      sequencing across diverse host, temporospatial, and population (i.e., single
      animal vs. mass mortality events) scales to improve our understanding of these
      globally emerging pathogens.

PMID- 27698175
TI  - Canine mammary minute oncocytomas with neuroendocrine differentiation associated
      with multifocal acinar cell oncocytic metaplasia.
AB  - Two solitary and minute tumors of 1 and 1.5 mm diameter were identified by
      microscopy in the left fourth mammary gland of a 13-year-old female Labrador
      Retriever dog, in addition to multiple mammary gland tumors. The former tumors
      were well circumscribed and were composed of small-to-large polyhedral neoplastic
      oncocytes with finely granular eosinophilic cytoplasm, and were arranged in solid
      nests separated by fine fibrovascular septa. Scattered lumina of variable sizes
      containing eosinophilic secretory material were evident. Cellular atypia was
      minimal, and no mitotic figures were visible. One tumor had several oncocytic
      cellular foci revealing cellular transition, with perivascular pseudorosettes
      consisting of columnar epithelial cells surrounding the fine vasculature.
      Scattered foci of mammary acinar cell hyperplasia showing oncocytic metaplasia
      were also observed. Immunohistochemically, the cytoplasm of neoplastic cells of
      the 2 microtumors showed diffuse immunoreactivity to anti-cytokeratin antibody
      AE1/AE3, and finely granular immunoreactivity for 60-kDa heat shock protein,
      mitochondrial membrane ATP synthase complex V beta subunit, and chromogranin A.
      One tumor also had oncocytic cellular foci forming perivascular pseudorosettes
      showing cellular membrane immunoreactivity for neural cell adhesion molecule. The
      tumors were negative for smooth muscle actin, neuron-specific enolase, vimentin,
      desmin, S100, and synaptophysin. Ultrastructural observation confirmed the
      abundant mitochondria in the cytoplasm of both neoplastic and hyperplastic cells,
      the former cells also having neuroendocrine granule-like electron-dense bodies.
      From these results, our case was diagnosed with mammary oncocytomas accompanied
      by neuroendocrine differentiation. Scattered foci of mammary oncocytosis might be
      related to the multicentric occurrence of these oncocytomas.

PMID- 27698176
TI  - A randomised controlled study of standard versus accelerated deflation of the
      Terumo radial band haemostasis device after transradial diagnostic cardiac
      catheterisation.
AB  - BACKGROUND: Radial access is the preferential access route in patients undergoing
      diagnostic coronary angiography. We hypothesised that we could reduce hospital
      stay and improve patient comfort by accelerated deflation of the radial
      compression device (Terumo radial band). AIMS: The aim of this study was to
      compare accelerated pressure reduction with a standard Terumo radial band
      protocol with regard to local bleeding complications and reported pain scores
      after cardiac catheterisation. METHODS: We performed a single centre prospective
      randomised trial to compare accelerated care to standard care for patients
      undergoing diagnostic catheterisation through radial access. Patients in the
      accelerated care group started deflation after 1 hour, with a 2 ml/10-minute
      interval. Patients in the standard care group started after 2 hours with
      additional steps of deflation at 3 and 4 hours. RESULTS: Of the 173 analysed
      patients 86 received accelerated care and 87 patients standard care. A total of
      19 patients had pulsatile bleeding, which occurred similarly in the two groups
      (standard care 11 vs. accelerated care 8, P=0.47). The time to Terumo radial band
      removal was on average 129 minutes shorter for accelerated care patients compared
      to standard care ( P<0.01). At 1 hour after Terumo radial band placement,
      accelerated care patients more often reported pain scores of 0 than standard care
      patients (89% vs. 74%, P=0.02). CONCLUSIONS: There was no increase in local
      bleedings in the accelerated pressure reduction of the Terumo radial band after
      diagnostic cardiac catheterisation, increasing patient comfort and reducing
      hospital stay. These findings will further facilitate the widespread
      implementation of radial access.

PMID- 27698177
TI  - Intramedullary Nailing and External Ring Fixation for Tibiotalocalcaneal
      Arthrodesis in Charcot Arthropathy.
AB  - BACKGROUND: Surgical strategies to address deformities of the ankle and hindfoot
      in patients with Charcot arthropathy include the use of retrograde intramedullary
      nails and ring fixators. The literature has not shown superiority of one
      technique over the other. This study presents a single surgeon's case series of
      Charcot arthropathy patients treated with either a ring fixator or retrograde
      intramedullary nail to achieve tibiotalocalcaneal arthrodesis. METHODS: We
      performed a retrospective analysis of 27 consecutive patients with Charcot
      arthropathy who underwent a tibiotalocalcaneal arthrodesis using either a
      retrograde intramedullary (IM) nail (n = 16 patients) or a ring fixator (RF) (n =
      11 patients) by a single surgeon. We report the rates of limb salvage
      complications requiring secondary surgery and fusion in both groups. The patient
      demographics and presence of medical comorbidities known to increase the risk of
      surgical complications were similar between groups. The mean duration of follow
      up for the retrograde nail group was 3.6 years and 2.2 years for the ring fixator
      group. RESULTS: The mean time to discharge from the hospital after the index
      surgical procedure was 2.7 days for the IM group and 4.6 days for the RF group.
      For the patients treated with a ring fixator, the mean time to removal of the
      frame after the initial application was 13.3 +/- 1.8 weeks. The limb salvage rate
      for the RF group was 9 of 11 patients whereas it was 15 of 16 in the IM group.
      Complications including deep infection, hardware failure, and symptomatic
      nonunion requiring revision surgery were common in the IM group, with 11 of 16
      patients requiring further surgery. Seven patients in the IM group required
      removal of the implant at a mean of 117.2 weeks after the index procedure because
      of the development of deep infection or nail cutout. In the RF group, only 1
      patient required revision surgery. Fusion rates were similar between both groups,
      with 10 of 16 patients fusing in the IM group and 7 of 11 in the RF group.
      CONCLUSION: Use of a retrograde intramedullary rod or ring fixator resulted in
      high rates of successful limb salvage when used for tibiotalocalcaneal
      arthrodesis in patients with Charcot arthropathy. However, in this study, the
      need for revision surgery was more frequent in the retrograde nail group compared
      to the ring fixator group. LEVEL OF EVIDENCE: Level III, retrospective
      comparative series.

PMID- 27698178
TI  - Correlation of Physical Performance and Patient-Reported Outcomes Following Total
      Ankle Arthroplasty.
AB  - BACKGROUND: Functional recovery following total ankle arthroplasty (TAA) is
      assessed with patient-reported metrics, but physical performance tests may allow
      for a more accurate assessment of patient function. We quantified correlations
      between patient-reported measures and physical performance tests in patients
      after TAA to determine the usefulness of physical performance tests in post-TAA
      assessment. METHODS: In total, 140 patients with end-stage ankle osteoarthritis
      were assessed prior to TAA and again at 12 and 24 months postoperatively. At each
      time point, the visual analog scale (VAS), Foot and Ankle Disability Index
      (FADI), American Orthopaedic Foot & Ankle Society (AOFAS), Short Musculoskeletal
      Function Assessment (SMFA), and Short-Form 36 (SF-36) scores were collected, as
      well as walking speed, Four-Square Step Test (FSST) times, and Short Physical
      Performance Battery (SPPB) balance scores. RESULTS: All but 1 (SF-36 general
      health component) of the patient-reported outcomes improved significantly from
      preoperative assessment to both 1 and 2 years postoperatively ( P < .001 in all
      cases). Walking speed, FSST times, and balance scores improved significantly
      across time ( P < .001 in all cases). Walking speed was moderately correlated
      with total SF-36 scores at both 1 and 2 years postoperatively ( P < .001 in both
      cases), both components of the SMFA at 1 year postoperatively ( P < .001 in both
      cases), and total AOFAS scores at 2 years postoperatively ( P = .001).
      CONCLUSION: The lack of strong correlations between the 2 sets of metrics
      indicates that they provide different information about a patient's recovery
      following TAA. Therefore, it is important to include both sets of metrics in post
      TAA assessments to better understand operative success and functional recovery.
      LEVEL OF EVIDENCE: Level IV, cohort study.

PMID- 27698179
TI  - Imaging of Bilateral Synchronous Testicular Tumors of Different Histologic Types
      and Implications for Surgical Management.
AB  - The clinical history and imaging and pathologic findings in 4 patients with
      bilateral synchronous testicular tumors of dissimilar histologic types were
      reviewed. All patients had a large scrotal mass on one side and a smaller nodule
      on the other one. The appearances of each pair of lesions were different enough
      to suggest that they could possibly be of different histologic types. The most
      important role of imaging, however, was its capability to guide the surgical
      approach to these patients: in 1 case, the smallest lesion was recognized as an
      epidermoid cyst; in 2 others a conservative approach was deemed possible, given
      the lesions' small volumes and peripheral locations.

PMID- 27698180
TI  - Use of Point-of-Care Ultrasound in the Emergency Department: Insights From the
      2012 Medicare National Payment Data Set.
AB  - OBJECTIVES: Point-of-care ultrasound is a valuable tool with potential to
      expedite diagnoses and improve patient outcomes in the emergency department.
      However, little is known about national patterns of adoption. This study examined
      nationwide point-of-care ultrasound reimbursement among emergency medicine (EM)
      practitioners and examined regional and practitioner level variations. METHODS:
      Data from the 2012 Center for Medicare and Medicaid Services Fee-for-Service
      Provider Utilization and Payment Data include all practitioners who received more
      than 10 Medicare Part B fee-for-service reimbursements for any Healthcare Common
      Procedure Coding System code in 2012. Odds ratios (ORs) and descriptive
      statistics were calculated to assess relationships between ultrasound
      reimbursement and practice location, nearby presence of an EM residency, and time
      elapsed since practitioner graduation. RESULTS: Of 52,928 unique EM
      practitioners, 391 (0.7%) received limited ultrasound reimbursements for a total
      of 16,389 scans in 2012. Urban counties had an OR of 5.4 (95% confidence
      interval, 3.8-7.8) for receiving point-of-care ultrasound reimbursements compared
      to rural counties. Counties with an EM residency had an OR of 84.7 (95%
      confidence interval, 42.6-178.8) for reimbursement compared to counties without.
      The OR for receiving reimbursement was independent of medical school graduation
      year (P = .83); however, recent graduates performed more scans (P = .02).
      CONCLUSIONS: A small minority of EM practitioners received reimbursements for
      point-of-care ultrasound from Medicare beneficiaries. These practitioners were
      more likely to reside in urban and academic settings. Future efforts should
      assess the degree to which our findings reflect either low point-of-care
      ultrasound use or low rates of billing for ultrasound examinations that are
      performed.

PMID- 27698181
TI  - Completion and Sensitivity of the Second-Trimester Fetal Anatomic Survey in Obese
      Gravidas.
AB  - OBJECTIVES: To estimate the effect of maternal body mass index (BMI) on the
      completion of fetal anatomic surveys before 20 weeks' estimated gestational age
      (GA). METHODS: We conducted a retrospective cohort study of singletons undergoing
      standard or detailed anatomic sonographic examinations from 2006 to 2014.
      Patients were categorized by ranges of BMI. The primary outcomes were completion
      of standard and detailed anatomic surveys before 20 weeks' estimated GA. The
      effect of the BMI category was assessed by the chi2 test for trends and analysis
      of variance. RESULTS: Of 15,313 patients, 5917 (38%) were obese, and 1581 (10%)
      had a BMI of 40 kg/m2 or higher. Standard (P < .01) and detailed (P < .01)
      surveys were less likely to be completed as the BMI category increased.
      Suboptimal visualization of the fetal chest (P < .01), abdomen (P < .01), and
      extremities (P < .01) significantly contributed to the decreased standard survey
      completion rates. Suboptimal visualization of the fetal head (P < .01) and chest
      (P < .01) significantly contributed to the decreased detailed survey completion
      rates. There was no statistically significant difference in the sensitivity of a
      completed standard or detailed anatomic survey for the detection of fetal
      anomalies. CONCLUSIONS: An increasing BMI category was associated with decreased
      completion of standard and detailed anatomic surveys by 20 weeks' estimated GA.
      Strategies to improve early visualization of the fetal head, chest, and abdomen
      in obese women should be investigated to promote anomaly detection and
      appropriate counseling.

PMID- 27698182
TI  - Sonographic Measurement of the Quadriceps Muscle in Patients With Chronic
      Obstructive Pulmonary Disease: Functional and Clinical Implications.
AB  - OBJECTIVES: The purpose of this study was to determine the association between
      functionality as assessed by the 6-minute walking test (6MWT), maximal voluntary
      contraction of the quadriceps (MVCQ), and quadriceps thickness and echo intensity
      as measured by sonography, in patients with chronic obstructive pulmonary disease
      (COPD). METHODS: Maximal voluntary contraction of the quadriceps and the
      thickness and echo intensity of the rectus femoris and vastus intermedius were
      evaluated in 20 patients with COPD. Functionality was assessed by the 6MWT.
      Differences between the evaluated muscles were determined by the Student t test.
      Pearson and Spearman rank correlation coefficients were used to analyze
      relationships between variables of interest, according to data characteristics.
      Finally, multivariate regression models were applied. RESULTS: There was a
      positive correlation between MVCQ and rectus femoris and vastus intermedius
      thickness (r = 0.427; P = .030; r = 0.469; P= .018, respectively) and a negative
      correlation between MVCQ and rectus femoris and vastus intermedius echo intensity
      (r= -0.500; P= .012; r= -0.482; P= .016). No correlation was found between MVCQ
      and the 6MWT (r = 0.319; P = .085). Multivariate regression analysis showed that
      the rectus femoris echo intensity, vastus intermedius echo intensity, and vastus
      intermedius thickness explained 70% of the variance in the distance walked during
      the 6MWT. CONCLUSIONS: These results indicate that, in patients with COPD, both
      quadriceps force and exercise capacity are associated with quantitative
      (thickness) and qualitative (echo intensity) characteristics of the quadriceps.
      Consequently, comprehensive assessments of peripheral muscles should
      simultaneously include both measurements.

PMID- 27698183
TI  - Resistive Index Variability in Anterior Cerebral Artery Measurements During Daily
      Transcranial Duplex Sonography: A Predictor of Cerebrovascular Complications in
      Infants Undergoing Extracorporeal Membrane Oxygenation?
AB  - OBJECTIVES: The purpose of this study was to determine the value of resistive
      index (RI) variability in predicting cerebrovascular complications during
      extracorporeal membrane oxygenation (ECMO). METHODS: This retrospective study
      included 36 infants treated by ECMO. The RI was measured on daily
      transfontanellar duplex sonography, obtained first without fontanel compression
      and then after gentle compression with the transducer. The age at ECMO
      cannulation, sex, gestational age at birth, method of delivery, indication, and
      type and duration of ECMO were recorded. RESULTS: There was a statistically
      significant difference in RI variability in infants who developed cerebrovascular
      complications as opposed to those who did not (P = .002). Resistive index
      variability of 10% or greater on any day was associated with an increased risk
      for cerebrovascular complications (P = .0482; chi2 = 3.9). Variability in the
      first 5 days was significantly higher than on following days (P < .0001). The age
      at ECMO cannulation showed a significant difference, with mean +/- SD values of
      1.1 +/- 0.9 days in the complications group and 2.7 +/- 2.2 days in the no
      complications group (P = .043). CONCLUSIONS: Resistive index variability of 10%
      or greater on any day had a statistically significant risk of cerebrovascular
      complication development. Extracorporeal membrane oxygenation cannulation at
      younger than 3 days conferred an increased risk of cerebrovascular complications.

PMID- 27698184
TI  - Physics and the Cell.

PMID- 27698186
TI  - beta-Catenin Mutations: Insights into the APC Pathway and the Power of Genetics.

PMID- 27698187
TI  - Blood Worth Bottling: Circulating Tumor DNA as a Cancer Biomarker.

PMID- 27698188
TI  - Endoplasmic Reticulum Stress Protein GRP78 Modulates Lipid Metabolism to Control
      Drug Sensitivity and Antitumor Immunity in Breast Cancer.
AB  - The unfolded protein response is an endoplasmic reticulum stress pathway mediated
      by the protein chaperone glucose regulated-protein 78 (GRP78). Metabolic analysis
      of breast cancer cells shows that GRP78 silencing increases the intracellular
      concentrations of essential polyunsaturated fats, including linoleic acid.
      Accumulation of fatty acids is due to an inhibition of mitochondrial fatty acid
      transport, resulting in a reduction of fatty acid oxidation. These data suggest a
      novel role of GRP78-mediating cellular metabolism. We validated the effect of
      GRP78-regulated metabolite changes by treating tumor-bearing mice with tamoxifen
      and/or linoleic acid. Tumors treated with linoleic acid plus tamoxifen exhibited
      reduced tumor area and tumor weight. Inhibition of either GRP78 or linoleic acid
      treatment increased MCP-1 serum levels, decreased CD47 expression, and increased
      macrophage infiltration, suggesting a novel role for GRP78 in regulating innate
      immunity. GRP78 control of fatty acid oxidation may represent a new homeostatic
      function for GRP78. Cancer Res; 76(19); 5657-70. (c)2016 AACR.

PMID- 27698190
TI  - Correction: Early Adaptation and Acquired Resistance to CDK4/6 Inhibition in
      Estrogen Receptor-Positive Breast Cancer.

PMID- 27698191
TI  - Correction: ASC-J9 Suppresses Renal Cell Carcinoma Progression by Targeting an
      Androgen Receptor-Dependent HIF2a/VEGF Signaling Pathway.

PMID- 27698189
TI  - miR-1298 Inhibits Mutant KRAS-Driven Tumor Growth by Repressing FAK and LAMB3.
AB  - Global miRNA functional screens can offer a strategy to identify synthetic lethal
      interactions in cancer cells that might be exploited therapeutically. In this
      study, we applied this strategy to identify novel gene interactions in KRAS
      mutant cancer cells. In this manner, we discovered miR-1298, a novel miRNA that
      inhibited the growth of KRAS-driven cells both in vitro and in vivo Using miR
      TRAP affinity purification technology, we identified the tyrosine kinase FAK and
      the laminin subunit LAMB3 as functional targets of miR-1298. Silencing of FAK or
      LAMB3 recapitulated the synthetic lethal effects of miR-1298 expression in KRAS
      driven cancer cells, whereas coexpression of both proteins was critical to rescue
      miR-1298-induced cell death. Expression of LAMB3 but not FAK was upregulated by
      mutant KRAS. In clinical specimens, elevated LAMB3 expression correlated with
      poorer survival in lung cancer patients with an oncogenic KRAS gene signature,
      suggesting a novel candidate biomarker in this disease setting. Our results
      define a novel regulatory pathway in KRAS-driven cancers, which offers a
      potential therapeutic target for their eradication. Cancer Res; 76(19); 5777-87.
      (c)2016 AACR.

PMID- 27698192
TI  - Treg/Th17 Cell Imbalance and IL-6 Profile in Patients With Unexplained Recurrent
      Spontaneous Abortion.
AB  - Regulatory T cells (Treg) and T helper 17 cells (Th17) are 2 distinct subsets of
      CD4+ T cells, which are mutually antagonistic in the immune response. Recently,
      dysregulation of these 2 cell subsets have been described in the pathogenesis of
      unexplained recurrent spontaneous abortion (URSA). The purpose of this study was
      to investigate whether the Treg/Th17 balance was perturbed in URSA patients and
      to explore contributing factors. We found that the proportion of Treg cells and
      expression of forkhead box P3 (Foxp3) messenger RNA (mRNA) were significantly
      lower in URSA patients than in healthy controls. However, the proportion of Th17
      cells and expression of retinoid-related orphan nuclear receptor-gammat (ROR
      gammat) mRNA were higher in URSA patients than in controls, revealing inverse
      correlation with Treg. The ratio of Treg/Th17 and Foxp3/ROR-gammat decreased in
      patients with URSA compared to healthy controls. The serum levels of interleukin
      (IL)-6 and IL-17A were significantly higher, whereas IL-10 was lower in URSA
      patients compared with controls, and the level of IL-6 showed a positive
      correlation with Th17, ROR-gammat and inverse correlation with Treg, Foxp3. The
      present study indicated that an imbalance between Treg and Th17 cells might be
      implicated in the pathogenesis of URSA and this seems to relate to elevation in
      serum IL-6 level.

PMID- 27698193
TI  - Estimating discharge dates using routinely collected data: improving the
      preparedness of parents of preterm infants for discharge home.
AB  - The length of stay for moderately preterm infants has progressively become
      shorter in the UK in recent years but staff still commonly inform parents that
      their baby will go home around their estimated date of delivery (EDD). Parents
      need as much notice as possible to prepare for the discharge of their baby, and
      to gain the necessary skills and knowledge to care for their infant safely. We
      report the use of routinely collected neonatal data to develop and implement a
      simple centile chart for date of discharge from hospital, which allows staff and
      parents to predict the likely discharge date more accurately for preterm infants,
      most of whom now go home more than 3 weeks before their EDD. This information
      allows better and timelier planning for discharge of such infants, by parents and
      staff.

PMID- 27698194
TI  - Automated FiO2 control: nice to have, or an essential addition to neonatal
      intensive care?

PMID- 27698196
TI  - Keeper of the clouds.

PMID- 27698197
TI  - Doctors seek legal advice over assisted dying.

PMID- 27698198
TI  - Alleged predatory publisher buys medical journals.

PMID- 27698195
TI  - Job insecurity and risk of diabetes: a meta-analysis of individual participant
      data.
AB  - BACKGROUND: Job insecurity has been associated with certain health outcomes. We
      examined the role of job insecurity as a risk factor for incident diabetes.
      METHODS: We used individual participant data from 8 cohort studies identified in
      2 open-access data archives and 11 cohort studies participating in the Individual
      Participant-Data Meta-analysis in Working Populations Consortium. We calculated
      study-specific estimates of the association between job insecurity reported at
      baseline and incident diabetes over the follow-up period. We pooled the estimates
      in a meta-analysis to produce a summary risk estimate. RESULTS: The 19 studies
      involved 140 825 participants from Australia, Europe and the United States, with
      a mean follow-up of 9.4 years and 3954 incident cases of diabetes. In the
      preliminary analysis adjusted for age and sex, high job insecurity was associated
      with an increased risk of incident diabetes compared with low job insecurity
      (adjusted odds ratio [OR] 1.19, 95% confidence interval [CI] 1.09-1.30). In the
      multivariable-adjusted analysis restricted to 15 studies with baseline data for
      all covariates (age, sex, socioeconomic status, obesity, physical activity,
      alcohol and smoking), the association was slightly attenuated (adjusted OR 1.12,
      95% CI 1.01-1.24). Heterogeneity between the studies was low to moderate (age-
      and sex-adjusted model: I2 = 24%, p = 0.2; multivariable-adjusted model: I2 =
      27%, p = 0.2). In the multivariable-adjusted analysis restricted to high-quality
      studies, in which the diabetes diagnosis was ascertained from electronic medical
      records or clinical examination, the association was similar to that in the main
      analysis (adjusted OR 1.19, 95% CI 1.04-1.35). INTERPRETATION: Our findings
      suggest that self-reported job insecurity is associated with a modest increased
      risk of incident diabetes. Health care personnel should be aware of this
      association among workers reporting job insecurity.

PMID- 27698199
TI  - Realizing the vision of patient-relevant clinical research.

PMID- 27698201
TI  - Abiding worries over federal health research.

PMID- 27698200
TI  - Managing smoking cessation.

PMID- 27698202
TI  - Persistent mild increase of human chorionic gonadotropin levels in a 31-year-old
      woman after spontaneous abortion.

PMID- 27698203
TI  - Blood Assay Predicts Response to Pembrolizumab.
AB  - Researchers found that the magnitude of reinvigoration of CD8+ T cells-the peak
      level of Ki67 after treatment-compared with tumor burden prior to treatment with
      the PD-1 inhibitor pembrolizumab correlated with clinical response in patients
      with advanced melanoma. If this finding is confirmed in a larger cohort of
      patients, the ratio of these two factors could be used to determine whether a
      patient should continue with pembrolizumab therapy or switch to a different
      treatment or combination of treatments.

PMID- 27698204
TI  - Muscular dystrophy drug looks set for commercial success despite clinical doubts.

PMID- 27698205
TI  - A reverse genetics cell-based evaluation of genes linked to healthy human tissue
      age.
AB  - We recently developed a binary (i.e., young vs. old) classifier using human
      muscle RNA profiles that accurately distinguished the age of multiple tissue
      types. Pathway analysis did not reveal regulators of these 150 genes, so we used
      reverse genetics and pharmacologic methods to explore regulation of gene
      expression. Using small interfering RNA, well-studied age-related factors (i.e.,
      rapamycin, resveratrol, TNF-alpha, and staurosporine), quantitative real-time PCR
      and clustering analysis, we studied gene-gene interactions in human skeletal
      muscle and renal epithelial cells. Individual knockdown of 10 different age genes
      yielded a consistent pattern of gene expression in muscle and renal cells,
      similar to in vivo. Potential epigenetic interactions included HIST1H3E
      knockdown, leading to decreased PHF19 and PCDH9, and increased ICAM5 in muscle
      and renal cells, while ICAM5 knockdown reduced HIST1H3E expression. Resveratrol,
      staurosporine, and TNF-alpha significantly regulated the in vivo aging genes,
      while only rapamycin perturbed the healthy-age gene expression signature in a
      manner consistent with in vivo. In vitro coordination of gene expression for this
      in vivo tissue age signature indicates a degree of direct coordination, and the
      observed link with mTOR activity suggests a direct link between a robust
      biomarker of healthy neuromuscular age and a major axis of life span in model
      systems.-Crossland, H., Atherton, P. J., Stromberg, A., Gustafsson, T., Timmons,
      J. A. A reverse genetics cell-based evaluation of genes linked to healthy human
      tissue age.

PMID- 27698206
TI  - Association between ATG16L1 gene polymorphism and the risk of Crohn's disease.
AB  - Objective To perform a meta-analysis to evaluate studies investigating the
      association between ATG16L1 gene polymorphism and Crohn's disease. Methods
      PubMed, Embase and Web of Science databases were searched for all studies
      focusing on the association of ATG16L1 and Crohn's disease. Combined odds ratios
      with 95% confidence intervals were calculated for four genetic models (allelic
      model: G allele versus A allele; additive model: GG versus AA; dominant model: GA
      + GG versus AA; recessive model: GG versus GA + AA) using either a random effects
      or fixed effects model. Results A total of 47 case-control studies involving 18
      638 cases and 30 181 controls were included in the final meta-analysis. There was
      a significant association between ATG16L1 and Crohn's disease for all four
      genetic models. Significant associations were also shown in subgroup analyses
      when stratified by study design (population- or hospital-based). Conclusion In
      this meta-analysis, the ATG16L1 genotype was significantly associated with the
      risk of developing Crohn's disease.

PMID- 27698207
TI  - High-flow nasal cannula therapy for adult patients.
AB  - High-flow nasal cannula (HFNC) oxygen therapy has several physiological
      advantages over traditional oxygen therapy devices, including decreased
      nasopharyngeal resistance, washing out of the nasopharyngeal dead space,
      generation of positive pressure in the pharynx, increasing alveolar recruitment
      in the lungs, humidification of the airways, increased fraction of inspired
      oxygen and improved mucociliary clearance. Recently, the use of HFNC in treating
      adult critical illness patients has significantly increased, and it is now being
      used in many patients with a range of different disease conditions. However,
      there are no established guidelines to direct the safe and effective use of HFNC
      for these patients. This review article summarizes the available published
      literature on the positive physiological effects, mechanisms of action, and the
      clinical applications of HFNC, compared with traditional oxygen therapy devices.
      The available literature suggests that HFNC oxygen therapy is an effective
      modality for the early treatment of critically adult patients.

PMID- 27698208
TI  - Regulation of steroidogenesis in fetal bovine ovaries: differential effects of LH
      and FSH.
AB  - In cattle, primordial follicles form before birth. Fetal ovarian capacity to
      produce progesterone and estradiol is high before follicle formation begins and
      decreases around the time follicles first appear (around 90 days of gestation).
      However, mechanisms that regulate steroid production during this time remain
      unclear. We hypothesized that LH stimulates progesterone and androgen production
      and that FSH stimulates aromatization of androgens to estradiol. To test this, we
      cultured pieces from fetal bovine ovaries for 10 days without or with exogenous
      hormones and then measured the accumulation of steroids in the culture medium by
      RIA. LH (100 ng/mL) alone increased the accumulation of progesterone,
      androstenedione, testosterone and estradiol. FSH (100 ng/mL) alone increased both
      progesterone and estradiol accumulation, but had no effect on androgens.
      Exogenous testosterone (0.5 uM) alone greatly increased estradiol accumulation
      and the combination of testosterone + FSH, but not testosterone + LH, increased
      estradiol relative to testosterone alone. Interestingly, exogenous testosterone
      and estradiol decreased progesterone accumulation in a dose-dependent manner.
      Because the highest dose of estradiol (0.5 uM) decreased progesterone
      accumulation, but increased both pregnenolone and androstenedione in the same
      cultures, endogenous estradiol may be a paracrine regulator of steroid synthesis.
      Together, these results confirm our initial hypotheses and indicate that LH
      stimulates androgen production in fetal bovine ovaries via the Delta5 pathway,
      whereas FSH stimulates aromatization of androgens to estradiol. These results are
      consistent with the two-cell, two-gonadotropin model of estradiol production by
      bovine preovulatory follicles, which suggests that the mechanisms regulating
      ovarian steroid production are established during fetal life.

PMID- 27698209
TI  - Assessing the Effectiveness of a School-Based Dental Clinic on the Oral Health of
      Children Who Lack Access to Dental Care.
AB  - This program evaluation examines the effectiveness of a school-based dental
      clinic. A repeated-measures design was used to longitudinally examine secondary
      data from participants ( N = 293). Encounter intensity was developed to normalize
      data. Multivariate analysis of variance and Kruskal-Wallis test were used to
      investigate the effect of encounter intensity on the change in decay,
      restorations, and treatment urgency. A Pearson's correlation was used to measure
      the strengths of association. Encounter intensity had a statistically significant
      effect on change in decay ( p = .005), restorations ( p = .000), and treatment
      urgency ( p = .001). As encounter intensity increased, there was a significant
      association with the decrease in decay (-.167), increase in restorations (.221),
      and reduction in referral urgency (-.188). Incorporating dental care into a
      school-based health center resulted in improved oral health in underserved
      children while overcoming barriers that typically restrict access. The
      collaboration of school nurses with the school-based dental clinic was an
      important element for maximizing student access to dental care.

PMID- 27698210
TI  - Research Priorities for School Nursing in the United Arab Emirates (UAE).
AB  - School nurses are challenged with more children having complex conditions, who
      are now surviving into school age. This is paralleled by a shift in focus of
      health systems toward primary care, and national efforts to develop the health
      care services, especially those offered to vulnerable populations. Being at the
      forefront of this change, school nurses in United Arab Emirates (UAE) are finding
      themselves under pressure to adapt to and facilitate these changes both by
      improving their practice and by contributing to its underpinning evidence. A
      cross-sectional design was used in this study in which 370 school nurses
      participated, identifying 11 research priorities. The three most important, as
      ranked by participants, were management of children with complex health-care
      needs; nutrition, obesity, and lifestyle issues of schoolchildren; and managing
      illnesses, injuries, and emergencies in schools and provision of medical support.
      These priorities should direct future research activities in the field.

PMID- 27698213
TI  - Suicide and the economic situation in Europe: are we experiencing the development
      of a 'reverse stigma'?
AB  - The prevailing picture in both the scientific literature and mass media is that
      the increase in unemployment acts as a generic risk factor on the entire
      population and increases the rate of suicide, suggesting that the socioeconomic
      environment is the determining factor and measures to improve it are the most
      suitable in the struggle to reduce the number of suicides. As a result,
      'horizontal' actions targeting the general population are proposed rather than
      'vertical' actions that target specific vulnerable groups. This is not only a
      mistake but it also constitutes a kind of 'reverse' stigma which deprives mental
      health patients of their right to receive special and targeted benefits,
      interventions and care, and deprives mental healthcare of valuable resources.

PMID- 27698211
TI  - Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8
      dependent mechanism.
AB  - BACKGROUND: Nicotine is a major oral irritant in smokeless tobacco products and
      has an aversive taste. Mentholated smokeless tobacco products are highly popular,
      suggesting that menthol increases their palatability and may facilitate
      initiation of product use. While menthol is known to reduce respiratory
      irritation by tobacco smoke irritants, it is not known whether this activity
      extends to oral nicotine and its aversive effects. STUDY DESIGN: The two-bottle
      choice drinking assay was used to characterise aversion and preference in C57BL/6
      mice to a range of menthol concentrations (10-200 ug/mL). Then, effects of
      menthol on oral nicotine aversion were determined. Responses were compared with
      those in mice deficient in the cold/menthol receptor, TRPM8, expressed in
      trigeminal sensory neurons innervating the oral cavity. RESULTS: Mice showed
      aversion to menthol concentrations of 100 ug/mL and above. When presented with a
      highly aversive concentration of nicotine (200 ug/mL), mice preferred solutions
      with 50 or 100 ug/mL menthol added over nicotine alone. In contrast to wild-type
      mice, Trpm8-/- showed a strong aversion to mentholated (100 ug/mL) nicotine (200
      ug/mL) and preferred nicotine alone. Trpm8-/- mice show aversion to lower
      concentrations of menthol than wild-type mice. CONCLUSIONS: Oral menthol can
      reduce the aversive effects of oral nicotine and, at higher concentrations, acts
      as an irritant by itself. Menthol's effects in relation to nicotine require
      TRPM8, the cool temperature sensing ion channel that activates analgesic and
      counterirritant mechanisms. These mechanisms may underlie preference for menthol
      containing smokeless tobacco products and may facilitate initiation of product
      use.

PMID- 27698212
TI  - The futility of risk prediction in psychiatry.
AB  - Significant efforts have been made to identify risk factors associated with
      suicide. However, the evidence suggests that risk categorisation may be of
      limited value, or worse, potentially harmful, confusing clinical thinking. We
      argue instead for a shift in focus towards real engagement with the individual
      patient, their specific problems and circumstances.

PMID- 27698214
TI  - Has DSM-5 saved PTSD from itself?
AB  - In 2007, Robert Spitzer considered validity challenges to the diagnosis of post
      traumatic stress disorder (PTSD), a construct that originated when he was Chair
      of DSM-III. Spitzer suggested changes for DSM-5, then in its planning stages, for
      the purpose of 'Saving PTSD from itself'. With years gone by, it can be asked if
      DSM-5 followed Spitzer's recommendations to advance our understanding of post
      traumatic disorder.

PMID- 27698216
TI  - Nise de Silveira (1905-1999), Brazilian psychiatrist and pioneer of
      rehabilitation psychiatry - extra.

PMID- 27698217
TI  - Deinstitutionalisation, imprisonment and homelessness.

PMID- 27698218
TI  - Deinstitutionalisation, imprisonment and homelessness.

PMID- 27698219
TI  - Author's reply.

PMID- 27698220
TI  - Trial of an intervention to reduce suicidal ideation and behaviour.

PMID- 27698221
TI  - Authors' reply.

PMID- 27698222
TI  - Evolutionary theories in disordered eating psychopathology.

PMID- 27698223
TI  - Authors' reply.

PMID- 27698227
TI  - Public Perception of Quality and Support for Required Access to Drinking Water in
      Schools and Parks.
AB  - PURPOSE: We assessed public support for required water access in schools and
      parks and perceived safety and taste of water in these settings to inform efforts
      to increase access to and consumption of tap water. DESIGN: Cross-sectional
      survey of the US public collected from August to November 2011. SETTING: Random
      digit-dialed telephone survey. PARTICIPANTS: Participants (n = 1218) aged 17 and
      older from 1055 US counties in 46 states. MEASURES: Perceived safety and taste of
      water in schools and parks as well as support for required access to water in
      these settings. ANALYSIS: Survey-adjusted perceived safety and taste as well as
      support for required access were estimated. RESULTS: There was broad support for
      required access to water throughout the day in schools (96%) and parks (89%). Few
      participants believed water was unsafe in schools (10%) or parks (18%).
      CONCLUSION: This study provides evidence of public support for efforts to
      increase access to drinking water in schools and parks and documents overall high
      levels of perceived taste and safety of water provided in these settings.

PMID- 27698228
TI  - Transcriptional Regulation of CYP2D6 Expression.
AB  - CYP2D6-mediated drug metabolism exhibits large interindividual variability.
      Although genetic variations in the CYP2D6 gene are well known contributors to the
      variability, the sources of CYP2D6 variability in individuals of the same
      genotype remain unexplained. Accumulating data indicate that transcriptional
      regulation of CYP2D6 may account for part of CYP2D6 variability. Yet, our
      understanding of factors governing transcriptional regulation of CYP2D6 is
      limited. Recently, mechanistic studies of increased CYP2D6-mediated drug
      metabolism in pregnancy revealed two transcription factors, small heterodimer
      partner (SHP) and Kruppel-like factor 9, as a transcriptional repressor and an
      activator, respectively, of CYP2D6. Chemicals that increase SHP expression (e.g.,
      retinoids and activators of farnesoid X receptor) were shown to downregulate
      CYP2D6 expression in the humanized mice as well as in human hepatocytes. This
      review summarizes the series of studies on the transcriptional regulation of
      CYP2D6 expression, potentially providing a basis to better understand the large
      interindividual variability in CYP2D6-mediated drug metabolism.

PMID- 27698230
TI  - Subclinical ischemic events in patients undergoing carotid artery stent
      placement: comparison of proximal and distal protection techniques.
AB  - OBJECTIVE: To determine the relative effectiveness of proximal and distal
      protection in prevention of cerebral ischemic events during carotid artery stent
      (CAS) placement using diffusion-weighted MRI (DW-MRI). METHODS: We analyzed data
      from patients who had undergone DW-MRI before and within 24 hours of CAS for
      symptomatic internal carotid artery (ICA) stenosis (with last ischemic events
      within 3 months). The study was performed prospectively; patients were not
      randomized, and were treated either with a proximal balloon occlusion system
      (Mo.Ma; Invatec, Roncadelle, Italy) or filter-type distal protection device
      (Spider device; ev3, Plymouth, Minnesota, USA). RESULTS: Of the 45 patients (mean
      age+/-SD: 66.9+/-9.8 years; 73.3% were men) who underwent CAS, 19 had proximal
      protection and 26 distal protection. New ischemic lesions were detected in 26/45
      patients on DW-MRI scans obtained within 24 hours after CAS. The proportion of
      patients with new lesions on DW-MRI at 24 hours was not different between the two
      groups (47.4% vs 65.4% for proximal and distal protection, respectively). The
      mean number of new ischemic lesions on post-CAS DW-MRI was non-significantly
      higher in patients who underwent CAS with distal protection (2.80+/-3.54 for
      proximal protection vs 4.96+/-5.11 for distal protection; p=0.12). The proportion
      of patients with new lesions >1 cm did not differ between the two groups (5.3%
      for proximal protection vs 11.5% for distal protection; p=0.62). There was no
      difference in the rates of ischemic stroke between patients who underwent CAS
      treatment using proximal and distal protection (5.3% vs 7.7%; p=1.000).
      CONCLUSIONS: We found a relatively high rate of new ischemic lesions in patients
      undergoing CAS with cerebral protection. There was no difference in the
      proportion of patients with new lesions between patients treated using distal
      protection and those treated using proximal protection.

PMID- 27698229
TI  - Stent-assisted coiling of cerebrovascular aneurysms: experience at a large
      tertiary care center with a focus on predictors of recurrence.
AB  - BACKGROUND: Stent-assisted coiling is commonly used to treat wide-necked and
      fusiform cerebral aneurysms. We evaluated our institutional experience with stent
      assisted coiling of cerebral aneurysms to elucidate potential risk factors for
      recurrence. METHODS: A retrospective analysis of patients undergoing stent
      assisted coiling of cerebral aneurysms from 2005 to 2012 resulted in 122 patients
      with 122 aneurysms. Demographic, peri-procedural, medical comorbidity, and follow
      up data were collected. Primary outcomes of interest were procedural safety,
      efficacy, and aneurysm recurrence. Univariate and multivariate logistic
      regression and chi2 tests determined the statistical significance of the risk
      factors. RESULTS: All 122 stent-assisted coiling procedures led to satisfactory
      obliteration of the aneurysm (3.3% complication rate). Twenty-one (17.2%)
      patients experienced recurrence at average follow-up of 297 days. Fifteen (71.4%)
      clinically significant recurrences required retreatment. Eleven of 30 (36.7%)
      procedures using Enterprise stents had recurrence compared with only 10 of 92
      (10.9%) procedures using Neuroform stents (p=0.001). Average coiling packing
      density (PD) was 20.3% with Enterprise stents and 22.5% with Neuroform stents
      (p=0.8). In multivariate logistic regression, recurrences requiring recoiling
      were significantly associated with Enterprise stents (OR 8.57, 95% CI 1.97 to
      37.19; p=0.004), females (OR 0.19, 95% CI 0.04 to 1.00; p=0.05), and
      postoperative dextran use (OR 8.42, 95% CI 1.40 to 50.58; p=0.02). Aneurysms with
      <20% PD were more likely to have a clinically significant recurrence than
      aneurysms with >20% PD (19% vs 5.1%; p=0.02). CONCLUSIONS: Stent-assisted coiling
      for wide-necked cerebral aneurysms has a high therapeutic success rate with low
      procedure-related morbidity and mortality. Clinically significant recurrences may
      occur more frequently with Enterprise stents, in aneurysms with low PD, and with
      post-procedural dextran use.

PMID- 27698231
TI  - A new index for the assessment of transverse sinus stenosis for diagnosing
      idiopathic intracranial hypertension.
AB  - BACKGROUND AND PURPOSE: To assess the role of MR venography (MRV) for detecting
      transverse sinus stenosis, to determine the importance of this finding in
      idiopathic intracranial hypertension (IIH), and to propose an index that
      contributes to this diagnosis. MATERIALS AND METHODS: We retrospectively assessed
      consecutive intracranial MRV of patients aged >18 years diagnosed with IIH
      according to the diagnostic criteria, between January 2010 and July 2012. The
      assessments were randomly analyzed by three radiologists. Stenoses in the right
      and left transverse sinuses were independently classified according to the
      following scale: 0, normal; 1, stenosis <33%; 2, stenosis 33-66%; 3, stenosis
      >66%; and 4, hypoplasia or agenesis. We established an index based on
      multiplication of the stenosis scale values for each transverse sinus. A point
      and range estimate of the sensitivity, specificity, and the area under the
      receiver operating characteristic curve was performed to obtain cut-off points to
      differentiate between controls and patients. RESULTS: 63 individuals were
      included in this study: 32 (50.8%) diagnosed with IIH (31 (96.9%) women and 1
      (3.1%) man) and 31 (49.2%) controls. According to all of the examiners, the IIH
      group showed a higher degree of stenosis than the control group. Index values >=4
      for a diagnosis of IIH had a sensitivity and specificity of 94.7% and 93.5%,
      respectively. CONCLUSIONS: MRV should be used to assess patients with suspected
      IIH, and bilateral transverse sinus stenosis should be considered for the
      diagnosis. The stenosis classifying index proposed here is a fast and accessible
      method for diagnosing IIH.

PMID- 27698232
TI  - Optimized CRISPR-Cas9 System for Genome Editing in Zebrafish.
AB  - This protocol describes how to generate and genotype mutants using an optimized
      CRISPR-Cas9 genome-editing system in zebrafish (CRISPRscan). Because single guide
      RNAs (sgRNAs) have variable efficiency when targeting specific loci, our protocol
      starts by explaining how to use the web tool CRISPRscan to design highly
      efficient sgRNAs. The CRISPRscan algorithm is based on the results of an
      integrated analysis of more than 1000 sgRNAs in zebrafish, which uncovered highly
      predictive factors that influence Cas9 activity. Next, we describe how to easily
      generate sgRNAs in vitro, which can then be injected in vivo to target specific
      loci. The use of highly efficient sgRNAs can lead to biallelic mutations in the
      injected embryos, causing lethality. We explain how targeting Cas9 to the
      germline increases viability by reducing somatic mutations. Finally, we combine
      two methods to identify F1 heterozygous fish carrying the desired mutations: (i)
      Mut-Seq, a method based on high-throughput sequencing to detect F0 founder fish;
      and (ii) a polymerase chain reaction-based fragment analysis method that
      identifies F1 heterozygous fish characterized by Mut-Seq. In summary, this
      protocol includes the steps to generate and characterize mutant zebrafish lines
      using the CRISPR-Cas9 genome engineering system.

PMID- 27698233
TI  - Detection of DNA Fragmentation in Apoptotic Cells by TUNEL.
AB  - Degradation of DNA into oligonucleosomal-sized fragments is a unique event in
      apoptosis that is orchestrated by caspase-activated DNase. Traditionally, this
      event is observed by resolving cellular DNA by gel electrophoresis, which results
      in a characteristic "ladder" pattern. However, this technique is time-consuming
      and cannot be used to quantitate the number of apoptotic cells in a sample.
      Terminal dUTP nick-end labeling (TUNEL) of fragmented DNA allows researchers to
      identify DNA fragmentation at the single-cell level. This method involves the
      specific addition of fluorescently labeled UTP to the 3'-end of the DNA fragments
      by terminal deoxynucleotidyl transferase. The TUNEL assay is both fast and
      sensitive. Here, we describe a protocol in which cells are treated with TUNEL
      reagent and counterstained with Hoechst 33342. In contrast to TUNEL, which only
      stains apoptotic cells, Hoechst 33342 stains the DNA of all cells.

PMID- 27698234
TI  - Measuring the DNA Content of Cells in Apoptosis and at Different Cell-Cycle
      Stages by Propidium Iodide Staining and Flow Cytometry.
AB  - All cells are created from preexisting cells. This involves complete duplication
      of the parent cell to create two daughter cells by a process known as the cell
      cycle. For this process to be successful, the DNA of the parent cell must be
      faithfully replicated so that each daughter cell receives a full copy of the
      genetic information. During the cell cycle, the DNA content of the parent cell
      increases as new DNA is synthesized (S phase). When there are two full copies of
      the DNA (G2/M phase), the cell splits to form two new cells (G0/G1 phase). As
      such, cells in different stages of the cell cycle have different DNA contents.
      The cell cycle is tightly regulated to safeguard the integrity of the cell and
      any cell that is defective or unable to complete the cell cycle is programmed to
      die by apoptosis. When this occurs, the DNA is fragmented into oligonucleosomal
      sized fragments that are disposed of when the dead cell is removed by
      phagocytosis. Consequently apoptotic cells have reduced DNA content compared with
      living cells. This can be measured by staining cells with propidium iodide (PI),
      a fluorescent molecule that intercalates with DNA at a specific ratio. The level
      of PI fluorescence in a cell is, therefore, directly proportional to the DNA
      content of that cell. This protocol describes the use of PI staining to determine
      the percentage of cells in each phase of the cell cycle and the percentage of
      apoptotic cells in a sample.

PMID- 27698235
TI  - Characterization of Protein-Protein Interactions Using Protein Microarrays.
AB  - Functional protein microarrays allow fast, straightforward, and efficient high
      throughput screening of protein-protein interactions. The microarray approach has
      outpaced other interaction methods, such as yeast two-hybrid screens, in part
      because of the vast amounts of information that can be obtained during a single
      assay. This protocol describes how to perform a binding assay for a protein of
      interest using a proteome microarray composed of thousands of functional,
      recombinant proteins adhered to a microchip.

PMID- 27698236
TI  - Characterization of RNA-Binding Proteins Using Protein Microarrays.
AB  - RNA-binding proteins (RBPs), along with target RNA, play a vital role in the
      regulation of cellular processing and are especially important in gene
      transcription and posttranscriptional regulation. Here, we present a high
      throughput method for rapid identification of RBPs for a given RNA using protein
      microarray technology. This protocol includes preparation of Cy5-labeled RNA
      probes, probe denaturing and refolding, and an RNA-binding assay as performed on
      a yeast protein microarray.

PMID- 27698237
TI  - Characterization of Lipid-Protein Interactions Using Nonquenched Fluorescent
      Liposomal Nanovesicles and Yeast Proteome Microarrays.
AB  - Studying lipid-protein interactions is central to understanding lipid signaling,
      a key regulatory system in cells. To better identify lipid-binding proteins, we
      developed a nonquenched fluorescent (NQF) liposome that is able to carry both
      fluorescent molecules and a lipid of interest. By combining the strength of NQF
      liposomes with protein microarray technology, the method presented here
      facilitates high-throughput screening of lipid-protein interactions. This
      protocol describes how to prepare NQF liposomes and apply the fabricated
      liposomes to yeast proteome microarrays.

PMID- 27698238
TI  - Posttranslational Modification Assays on Functional Protein Microarrays.
AB  - Protein microarray technology provides a straightforward yet powerful strategy
      for identifying substrates of posttranslational modifications (PTMs) and studying
      the specificity of the enzymes that catalyze these reactions. Protein microarray
      assays can be designed for individual enzymes or a mixture to establish
      connections between enzymes and substrates. Assays for four well-known PTMs
      phosphorylation, acetylation, ubiquitylation, and SUMOylation-have been developed
      and are described here for use on functional protein microarrays. Phosphorylation
      and acetylation require a single enzyme and are easily adapted for use on an
      array. The ubiquitylation and SUMOylation cascades are very similar, and the
      combination of the E1, E2, and E3 enzymes plus ubiquitin or SUMO protein and ATP
      is sufficient for in vitro modification of many substrates.

PMID- 27698239
TI  - Preparation of Yeast DNA Sequencing Libraries.
AB  - This protocol provides a detailed description of how to prepare a DNA sequencing
      library from yeast genomic DNA for use with the Illumina sequencing platform.
      This method does not require purchase of Illumina kits for library preparation
      but instead employs specific reagents purchased largely from New England BioLabs,
      which significantly reduces the cost of library preparation. Although we assume
      here that users intend to generate libraries with ~400-bp insert sizes for paired
      end sequencing, it is relatively straightforward to modify the shearing and size
      selection steps for longer or shorter inserts.

PMID- 27698241
TI  - Reporter Gene Silencing Assays in Fission Yeast.
AB  - Reporter gene silencing assays provide a facile method for assessing the function
      of heterochromatin in Schizosaccharomyces pombe They use strains containing
      auxotrophic markers (commonly ura4+ or ade6+) located within a heterochromatic
      region. Transcriptional silencing of these reporters can be assessed by plating
      serial dilutions of cells onto minimal agar. In addition, silencing of ura4+
      renders cells resistant to 5-fluoroorotic acid (5-FOA) and ade6+ silencing
      results in red colony color on adenine-limiting agar. Various reporters for each
      of the major heterochromatic domains (telomeres, centromeres, and the mating type
      locus) are available and, importantly, transcriptional silencing is correlated
      with the proper function of these regions.

PMID- 27698242
TI  - Analysis of Schizosaccharomyces pombe Heterochromatin-Associated Short
      Interfering RNAs.
AB  - An important aspect of RNAi-mediated heterochromatin assembly is the production
      of short interfering RNAs (siRNAs) in cis at the heterochromatic target. These
      populations of small RNAs (20-30 nt) can be detected via northern blot analysis
      with radiolabeled RNA probes corresponding to the siRNAs. Most heterochromatin
      associated siRNAs originate from both strands of the pericentromeric dg and dh
      repeats. Thus, production of RNA probes by in vitro transcription utilizes a DNA
      template with sequences corresponding to either dg or dh repeats. Alternatively,
      radiolabeled DNA probes, which are somewhat easier to prepare, may be used. A
      control probe against a small RNA, such as a tRNA, may also be prepared for
      loading. More recently genome-scale analysis using next-generation sequencing
      platforms has enabled the detection of rare siRNAs at sites other than the major
      heterochromatin domains. This protocol describes procedures for the extraction of
      small RNAs from Schizosaccharomyces pombe and their detection by northern blot
      analysis.

PMID- 27698240
TI  - Combining Optogenetics and Electrophysiology to Analyze Projection Neuron
      Circuits.
AB  - A set of methods is described for channelrhodopsin-2 (ChR2)-based synaptic
      circuit analysis that combines photostimulation of virally transfected
      presynaptic neurons' axons with whole-cell electrophysiological recordings from
      retrogradely labeled postsynaptic neurons. The approach exploits the preserved
      photoexcitability of ChR2-expressing axons in brain slices and can be used to
      assess either local or long-range functional connections. Stereotaxic injections
      are used both to express ChR2 selectively in presynaptic axons of interest (using
      rabies virus [RV] or adeno-associated virus [AAV]) and to label two types of
      postsynaptic projection neurons of interest with fluorescent retrograde tracers.
      In brain slices, tracer-labeled postsynaptic neurons are targeted for whole-cell
      electrophysiological recordings, and synaptic connections are assessed by
      sampling voltage or current responses to light-emitting diode (LED)
      photostimulation of ChR2-expressing axons. The data are analyzed to estimate the
      relative amplitude of synaptic input and other connectivity parameters.
      Pharmacological and electrophysiological manipulations extend the versatility of
      the basic approach, allowing the dissection of monosynaptic versus disynaptic
      responses, excitatory versus inhibitory responses, and more. The method enables
      rapid, quantitative characterization of synaptic connectivity between defined pre
      and postsynaptic classes of neurons.

PMID- 27698243
TI  - Preparation of Plasmid DNA by Alkaline Lysis with Sodium Dodecyl Sulfate:
      Minipreps.
AB  - In this protocol, plasmid DNA is isolated from small-scale (1-2 mL) bacterial
      cultures. Yields vary between 100 and 5 ug of DNA, depending on the copy number
      of the plasmid. Miniprep DNA is sufficiently pure for use as a substrate or
      template in many in vitro enzymatic reactions. However, further purification is
      required if the plasmid DNA is used as the substrate in sequencing reactions.

PMID- 27698244
TI  - High-Throughput Yeast Strain Sequencing.
AB  - The original yeast genome sequencing project was a monumental task, spanning
      several years, which resulted in the first sequenced eukaryotic genome. The 12
      Mbp reference sequence was generated from yeast strain S288c and was of extremely
      high quality. In the years since it was published, sequencing technology has
      advanced apace, such that it is within the reach of most labs to sequence yeast
      strains of interest almost as a matter of standard practice, either via core
      facilities at their institution or through commercial sequencing services.
      Because of the availability of the high-quality reference sequence (which itself
      has received approximately 1500 updates derived from high-throughput sequencing
      data), reliable identification of differences between a strain of interest and
      the reference is relatively straightforward, at least for the nonrepetitive
      regions of the genome. In this introduction, we describe current high-throughput
      sequencing technology and methods for analysis of the resulting data.

PMID- 27698245
TI  - Protein Microarrays: Flexible Tools for Scientific Innovation.
AB  - Protein microarrays have emerged as a powerful tool for the scientific community,
      and their greatest advantage lies in the fact that thousands of reactions can be
      performed in a parallel and unbiased manner. The first high-density protein
      microarray, dubbed the "yeast proteome array," consisted of approximately 5800
      full-length yeast proteins and was initially used to identify protein-lipid
      interactions. Further assays were subsequently developed to allow measurement of
      protein-DNA, protein-RNA, and protein-protein interactions, as well as four well
      known posttranslational modifications: phosphorylation, acetylation,
      ubiquitylation, and SUMOylation. In this introduction, we describe the advent of
      high-density protein microarrays, as well as current methods for assessing a wide
      variety of protein interactions and posttranslational modifications.

PMID- 27698246
TI  - Optimization Strategies for the CRISPR-Cas9 Genome-Editing System.
AB  - The CRISPR-Cas9 system uncovered in bacteria has emerged as a powerful genome
      editing technology in eukaryotic cells. It consists of two components-a single
      guide RNA (sgRNA) that directs the Cas9 endonuclease to a complementary DNA
      target site. Efficient targeting of individual genes requires highly active
      sgRNAs. Recent efforts have made significant progress in understanding the
      sequence features that increase sgRNA activity. In this introduction, we
      highlight advancements in the field of CRISPR-Cas9 targeting and discuss our web
      tool CRISPRscan, which predicts the targeting activity of sgRNAs and improves the
      efficiency of the CRISPR-Cas9 system for in vivo genome engineering.

PMID- 27698247
TI  - The impact of multiple sclerosis severity on health state utility values:
      Evidence from Australia.
AB  - BACKGROUND: The measurement of health state utility values (HSUVs) for a
      representative sample of Australian people with multiple sclerosis (MS) has not
      previously been performed. OBJECTIVES: Our main aim was to quantify the HSUVs for
      different levels of disease severities in Australian people with MS. METHOD:
      HSUVs were calculated by employing a 'judgement-based' method that essentially
      creates EQ-5D-3L profiles based on WHOQOL-100 responses and then applying utility
      weights to each level in each dimension. A stepwise linear regression was used to
      evaluate the relationship between HSUVs and disease severity, classified as mild
      (Expanded Disability Status Scale (EDSS) levels: 0-3.5), moderate (EDSS levels: 4
      6) and severe (EDSS levels: 6.5-9.5). RESULTS: Mean HSUV for all people with MS
      was 0.53 (95% confidence interval (CI): 0.52-0.54). Utility decreased with
      increasing disease severity: 0.61 (95% CI: 0.60-0.62), 0.51 (95% CI: 0.50-0.52)
      and 0.40 (95% CI: 0.38-0.43) for mild, moderate and severe disease, respectively.
      Adjusted differences in mean HSUV between the three severity groups were
      statistically significant. CONCLUSION: For the first time in Australia, we have
      quantified the impact of increasing severity of MS on health utility of people
      with MS. The HSUVs we have generated will be useful in further health economic
      analyses of interventions that slow progression of MS.

PMID- 27698249
TI  - Prevalence of Shiga toxin-producing and enteropathogenic Escherichia coli marker
      genes in diarrhoeic stools in a New Zealand catchment area.
AB  - BACKGROUND: Shiga toxin-producing (STEC) and enteropathogenic (EPEC) Escherichia
      coli are gastrointestinal pathogens causing diarrhoeal and extraintestinal
      disease. Due to lack of EPEC screening and use of Sorbitol-MacConkey (SMAC) agar
      in faecal screening, the true prevalence of EPEC and non-O157 STEC in New Zealand
      diarrhoeal cases is unknown. METHODS: Diarrhoeic stools sourced from Dunedin
      hospital were pre-enriched, DNA extracted with Chelex-100 resin and screened
      using a multiplex TaqMan quantitative PCR assay amplifying stx1, sxt2 and EPEC
      (eae) gene markers. RESULTS: Of the 522 diarrhoeic samples surveyed, 8 (1.53%)
      were PCR positive for stx1/stx2 and 23 (4.41%) were positive for eae. Six (75%)
      of the stx+ samples were uncommon non-O157 serotypes, and the remainder were
      found to be positive for both O103 and O157 STEC somatic antigens. CONCLUSIONS:
      Results revealed shortcomings in current screening protocols for pathogenic E.
      coli; SMAC is not sufficiently discriminatory to detect emergent STEC serotypes
      and EPEC likely has an unappreciated role in cases of diarrhoea in New Zealand.

PMID- 27698250
TI  - Infrequent expression of CD15 by classical Hodgkin's lymphomas in Taiwan.

PMID- 27698248
TI  - In vivo detection of connectivity between cortical and white matter lesions in
      early MS.
AB  - BACKGROUND: The relationship between cortical lesions (CLs) and white matter
      lesions (WMLs) in multiple sclerosis (MS) is poorly understood. Pathological
      studies support a topographical association between CLs and underlying
      subcortical WMLs and suggest CLs may play a role in both disease initiation and
      progression. We hypothesized that cortical MS lesions are physically connected to
      white matter MS lesions via axonal connections. OBJECTIVE: To assess the presence
      of CL-WML connectivity utilizing novel magnetic resonance imaging (MRI)
      methodology. METHODS: In all, 28 relapsing-remitting MS patients and 25 controls
      received 3 T MRI scans, including double inversion recovery (DIR) for CL
      detection coupled with diffusion tensor imaging (DTI). CL and WML maps were
      created, and DTI was used to calculate inter-lesional connectivity and volumetric
      connectivity indices. RESULTS: All patients showed inter-lesional WML
      connectivity (median 76% of WMLs connected to another WML; interquartile range
      (IQR), 58%-88%). On average, 52% of detected CLs per patient were connected to at
      least one WML (IQR, 42%-71%). Volumetric connectivity analysis showed
      significantly elevated cortical lesion ratios in MS patients (median, 2.3; IQR,
      1.6-3.3) compared to null MS and healthy control datasets ( p < 0.001).
      CONCLUSION: These findings provide strong evidence of inter-lesional connectivity
      between CLs and WMLs, supporting our hypothesis of intrinsic CL-WML connectivity.

PMID- 27698251
TI  - Critical evaluation of KCNJ3 gene product detection in human breast cancer: mRNA
      in situ hybridisation is superior to immunohistochemistry.
AB  - Increased expression levels of KCNJ3 have been correlated with lymph node
      metastases and poor prognosis in patients with breast cancer, suggesting a
      prognostic role of KCNJ3 We aimed to establish protocols for the detection of
      KCNJ3 in formalin-fixed, paraffin-embedded (FFPE) breast cancer tissue. Several
      antibodies were tested for sensitivity and specificity by western blot, followed
      by optimisation of the immunohistochemistry (IHC) procedure and establishment of
      KCNJ3 mRNA in situ hybridisation (ISH). Methods were validated by processing 15
      FFPE breast cancer samples for which microarray data were available. Spearman's
      rank correlation analysis resulted in borderline significant correlation for IHC
      versus ISH (rS: 0.625; p<0.05) and IHC versus microarray (rS: 0.668; p<0.01), but
      in significant correlation for ISH versus microarray (rS: 0.861; p<0.001). The
      ISH method was superior to IHC, regarding robustness, sensitivity and specificity
      and will aid to further study expression levels of KCNJ3 in both malignant and
      physiological conditions.

PMID- 27698254
TI  - Corrigendum: A genome-wide analysis of common fragile sites: What features
      determine chromosomal instability in the human genome?

PMID- 27698252
TI  - Secretory leukocyte protease inhibitor promising protective roles in obesity
      associated atherosclerosis.
AB  - Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor, which
      was most commonly examined in mucosal fluids such as saliva, is a versatile
      molecule and plays non-redundant roles. In addition to its anti-protease
      activity, SLPI has been shown to express anti-bacterial, anti-viral, anti-fungal,
      and anti-inflammatory properties as well as participating in innate and adaptive
      immune responses, most of which has been well documented. Recently, it is
      reported that SLPI is expressed in adipocytes and adipose tissue where it could
      play an important feedback role in the resolution of inflammation. Furthermore,
      circulating SLPI has been shown to correlate with progressive metabolic
      dysfunction. Moreover, adenoviral gene delivery of elafin and SLPI attenuates
      nuclear factor-kappaB-dependent inflammatory responses of human endothelial cells
      and macrophages to atherogenic stimuli. This review contributes to unraveling the
      protective role of SLPI in obesity-related atherosclerosis development, and the
      potential role in preventing arterial plaque rupture.

PMID- 27698253
TI  - A Legume TOR Protein Kinase Regulates Rhizobium Symbiosis and Is Essential for
      Infection and Nodule Development.
AB  - The target of rapamycin (TOR) protein kinase regulates metabolism, growth, and
      life span in yeast, animals, and plants in coordination with nutrient status and
      environmental conditions. The nutrient-dependent nature of TOR functionality
      makes this kinase a putative regulator of symbiotic associations involving
      nutrient acquisition. However, TOR's role in these processes remains to be
      understood. Here, we uncovered the role of TOR during the bean (Phaseolus
      vulgaris)-Rhizobium tropici (Rhizobium) symbiotic interaction. TOR was expressed
      in all tested bean tissues, with higher transcript levels in the root meristems
      and senesced nodules. We showed TOR promoter expression along the progressing
      infection thread and in the infected cells of mature nodules. Posttranscriptional
      gene silencing of TOR using RNA interference (RNAi) showed that this gene is
      involved in lateral root elongation and root cell organization and also alters
      the density, size, and number of root hairs. The suppression of TOR transcripts
      also affected infection thread progression and associated cortical cell
      divisions, resulting in a drastic reduction of nodule numbers. TOR-RNAi resulted
      in reduced reactive oxygen species accumulation and altered CyclinD1 and CyclinD3
      expression, which are crucial factors for infection thread progression and nodule
      organogenesis. Enhanced expression of TOR-regulated ATG genes in TOR-RNAi roots
      suggested that TOR plays a role in the recognition of Rhizobium as a symbiont.
      Together, these data suggest that TOR plays a vital role in the establishment of
      root nodule symbiosis in the common bean.

PMID- 27698255
TI  - Fabrication and characterization of metal stent coating with drug-loaded
      nanofiber film for gallstone dissolution.
AB  - Stent insertion and chemical agents of ethylene diamine tetraacetic acid and
      sodium cholate for dissolving common bile duct stone diseases through extra
      biliary tract infusion have been believed a relatively effective therapeutics for
      the clinical symptom. Core-shell nanofibers produced by co-axial electrospinning
      to deliver chemical drugs, biomacromolecules, genes and even cells have been
      reported for various advanced drug delivery system and tissue engineering
      applications. In the present study, poly (lactide-co-E-caprolactone) (PLCL) core
      shell nanofiber-coated film of stent, loaded with ethylene diamine tetraacetic
      acid and sodium cholate in core layer, was fabricated by co-axial electrospinning
      for treating gallstone disease. Image of laser scanning confocal microscopy and
      transmission electron microscopy demonstrated core-shell structure of drug-loaded
      nanofiber. Fourier transform infrared spectra and the thermogravimetric analysis
      proved ethylene diamine tetraacetic acid and sodium cholate to be successfully
      loaded in nanofibers. Morphology of nanofibers after a period of degradation
      still keeps good shape. Drugs can continuously release for around five days,
      which was proved significant effectiveness for dissolving gallstone. Besides,
      unobvious cytotoxicity was exhibited from MTT results and cell kept good
      morphology in vitro research. The present coated stent showed a bright prospect
      for dissolving the biliary stone.

PMID- 27698256
TI  - Development and Testing of a Conceptual Model Regarding Men's Access to Health
      Care.
AB  - Epidemiologic data suggest men often experience excessive morbidity and early
      mortality, possibly compromising family and community health over the lifespan.
      Moreover, the negative financial/economic consequences affected by poor male
      health outcomes also has been of great concern in the United States and abroad.
      Early and consistent access to preventative health care may improve health
      outcomes; however, men are far less likely to access these services. The purpose
      of this study was to understand what factors preclude men from accessing health
      care. We surveyed 485 participants using a 58-item online survey built from a
      conceptual model previously developed by the researchers using hegemonic
      masculinity theory, the theory of normative contentment, and the health belief
      model. For men, three items significantly ( ps < .05) predicted whether they had
      seen a health care provider in the past year: "I/Men do not access healthcare
      because I do not think there is anything wrong with me," "My health is only about
      me," and "I/Men do not access healthcare because most men in my family do not
      access healthcare." Other correlations of practical significance also were noted.
      Results suggest gender norms and masculine ideals may play a primary role in how
      men access preventative health care. Future programming targeting males should
      consider barriers and plan programs that are gender-sensitive in addition to
      being gender-specific. Clinical implications are discussed.

PMID- 27698257
TI  - Subjective Listening Effort and Electrodermal Activity in Listening Situations
      with Reverberation and Noise.
AB  - Disturbing factors like reverberation or ambient noise can impair speech
      recognition and raise the listening effort needed for successful communication in
      daily life. Situations with high listening effort are thought to result in
      increased stress for the listener. The aim of this study was to explore possible
      measures to determine listening effort in situations with varying background
      noise and reverberation. For this purpose, subjective ratings of listening
      effort, speech recognition, and stress level, together with the electrodermal
      activity as a measure of the autonomic stress reaction, were investigated. It was
      expected that the electrodermal activity would show different stress levels in
      different acoustic situations and might serve as an alternative to subjective
      ratings. Ten young normal-hearing and 17 elderly hearing-impaired subjects
      listened to sentences from the Oldenburg sentence test either with stationary
      background noise or with reverberation. Four listening situations were generated,
      an easy and a hard one for each of the two disturbing factors, which were related
      to each other by the Speech Transmission Index. The easy situation resulted in
      100% and the hard situation resulted in 30 to 80% speech recognition. The results
      of the subjective ratings showed significant differences between the easy and the
      hard listening situations in both subject groups. Two methods of analyzing the
      electrodermal activity values revealed similar, but nonsignificant trends.
      Significant correlations between subjective ratings and physiological
      electrodermal activity data were observed for normal-hearing subjects in the
      noise situation.

PMID- 27698258
TI  - Time-Varying Distortions of Binaural Information by Bilateral Hearing Aids:
      Effects of Nonlinear Frequency Compression.
AB  - In patients with bilateral hearing loss, the use of two hearing aids (HAs) offers
      the potential to restore the benefits of binaural hearing, including sound source
      localization and segregation. However, existing evidence suggests that bilateral
      HA users' access to binaural information, namely interaural time and level
      differences (ITDs and ILDs), can be compromised by device processing. Our
      objective was to characterize the nature and magnitude of binaural distortions
      caused by modern digital behind-the-ear HAs using a variety of stimuli and HA
      program settings. Of particular interest was a common frequency-lowering
      algorithm known as nonlinear frequency compression, which has not previously been
      assessed for its effects on binaural information. A binaural beamforming
      algorithm was also assessed. Wide dynamic range compression was enabled in all
      programs. HAs were placed on a binaural manikin, and stimuli were presented from
      an arc of loudspeakers inside an anechoic chamber. Stimuli were broadband noise
      bursts, 10-Hz sinusoidally amplitude-modulated noise bursts, or consonant-vowel
      consonant speech tokens. Binaural information was analyzed in terms of ITDs,
      ILDs, and interaural coherence, both for whole stimuli and in a time-varying
      sense (i.e., within a running temporal window) across four different frequency
      bands (1, 2, 4, and 6 kHz). Key findings were: (a) Nonlinear frequency
      compression caused distortions of high-frequency envelope ITDs and significantly
      reduced interaural coherence. (b) For modulated stimuli, all programs caused time
      varying distortion of ILDs. (c) HAs altered the relationship between ITDs and
      ILDs, introducing large ITD-ILD conflicts in some cases. Potential perceptual
      consequences of measured distortions are discussed.

PMID- 27698260
TI  - Rapid Release From Listening Effort Resulting From Semantic Context, and Effects
      of Spectral Degradation and Cochlear Implants.
AB  - People with hearing impairment are thought to rely heavily on context to
      compensate for reduced audibility. Here, we explore the resulting cost of this
      compensatory behavior, in terms of effort and the efficiency of ongoing
      predictive language processing. The listening task featured predictable or
      unpredictable sentences, and participants included people with cochlear implants
      as well as people with normal hearing who heard full-spectrum/unprocessed or
      vocoded speech. The crucial metric was the growth of the pupillary response and
      the reduction of this response for predictable versus unpredictable sentences,
      which would suggest reduced cognitive load resulting from predictive processing.
      Semantic context led to rapid reduction of listening effort for people with
      normal hearing; the reductions were observed well before the offset of the
      stimuli. Effort reduction was slightly delayed for people with cochlear implants
      and considerably more delayed for normal-hearing listeners exposed to spectrally
      degraded noise-vocoded signals; this pattern of results was maintained even when
      intelligibility was perfect. Results suggest that speed of sentence processing
      can still be disrupted, and exertion of effort can be elevated, even when
      intelligibility remains high. We discuss implications for experimental and
      clinical assessment of speech recognition, in which good performance can arise
      because of cognitive processes that occur after a stimulus, during a period of
      silence. Because silent gaps are not common in continuous flowing speech, the
      cognitive/linguistic restorative processes observed after sentences in such
      studies might not be available to listeners in everyday conversations, meaning
      that speech recognition in conventional tests might overestimate sentence
      processing capability.

PMID- 27698259
TI  - The Prediction of Speech Recognition in Noise With a Semi-Implantable Bone
      Conduction Hearing System by External Bone Conduction Stimulation With Headband:
      A Prospective Study.
AB  - Semi-implantable transcutaneous bone conduction devices are treatment options for
      conductive and mixed hearing loss (CHL/MHL). For counseling of patients,
      realistic simulation of the functional result is desirable. This study compared
      speech recognition in noise with a semi-implantable transcutaneous bone
      conduction device to external stimulation with a bone conduction device fixed by
      a headband. Eight German-language adult patients were enrolled after a semi
      implantable transcutaneous bone conduction device (Bonebridge, Med-El) was
      implanted and fitted. Patients received a bone conduction device for external
      stimulation (Baha BP110, Cochlear) fixed by a headband for comparison. The main
      outcome measure was speech recognition in noise (Oldenburg Sentence Test). Pure
      tone audiometry was performed and subjective benefit was assessed using the
      Glasgow Benefit Inventory and Abbreviated Profile of Hearing Aid Benefit
      questionnaires. Unaided, patients showed a mean signal-to-noise ratio threshold
      of 4.6 +/- 4.2 dB S/N for speech recognition. The aided results were -3.3 +/- 7.2
      dB S/N by external bone conduction stimulation and -1.2 +/- 4.0 dB S/N by the
      semi-implantable bone conduction device. The difference between the two devices
      was not statistically significant, while the difference was significant between
      unaided and aided situation for both devices. Both questionnaires for subjective
      benefit favored the semi-implantable device over external stimulation. We
      conclude that it is possible to simulate the result of speech recognition in
      noise with a semi-implantable transcutaneous bone conduction device by external
      stimulation. This should be part of preoperative counseling of patients with
      CHL/MHL before implantation of a bone conduction device.

PMID- 27698261
TI  - A Binaural Grouping Model for Predicting Speech Intelligibility in Multitalker
      Environments.
AB  - Spatially separating speech maskers from target speech often leads to a large
      intelligibility improvement. Modeling this phenomenon has long been of interest
      to binaural-hearing researchers for uncovering brain mechanisms and for improving
      signal-processing algorithms in hearing-assistive devices. Much of the previous
      binaural modeling work focused on the unmasking enabled by binaural cues at the
      periphery, and little quantitative modeling has been directed toward the grouping
      or source-separation benefits of binaural processing. In this article, we propose
      a binaural model that focuses on grouping, specifically on the selection of time
      frequency units that are dominated by signals from the direction of the target.
      The proposed model uses Equalization-Cancellation (EC) processing with a binary
      decision rule to estimate a time-frequency binary mask. EC processing is carried
      out to cancel the target signal and the energy change between the EC input and
      output is used as a feature that reflects target dominance in each time-frequency
      unit. The processing in the proposed model requires little computational
      resources and is straightforward to implement. In combination with the Coherence
      based Speech Intelligibility Index, the model is applied to predict the speech
      intelligibility data measured by Marrone et al. The predicted speech reception
      threshold matches the pattern of the measured data well, even though the
      predicted intelligibility improvements relative to the colocated condition are
      larger than some of the measured data, which may reflect the lack of internal
      noise in this initial version of the model.

PMID- 27698263
TI  - Changes in Health-Related Quality of Life During Rehabilitation in Patients With
      Operable Lung Cancer: A Feasibility Study (PROLUCA).
AB  - INTRODUCTION: Surgical resection in patients with non-small cell lung cancer
      (NSCLC) may be associated with significant morbidity, functional limitations, and
      decreased quality of life. OBJECTIVES: The objective is to present health-related
      quality of life (HRQoL) changes over time before and 1 year after surgery in
      patients with NSCLC participating in a rehabilitation program. METHODS: Forty
      patients with NSCLC in disease stage I to IIIa, referred for surgical resection
      at the Department of Cardiothoracic Surgery RT, Rigshospitalet, were included in
      the study. The rehabilitation program comprised supervised group exercise
      program, 2 hours weekly for 12 weeks, combined with individual counseling. The
      study endpoints were self-reported HRQoL (Functional Assessment of Cancer Therapy
      Lung, European Organization for Research and Treatment in Cancer-Quality of Life
      Questionnaire-QLQ-C30, Short-Form-36) and self-reported distress, anxiety,
      depression, and social support (National Comprehensive Cancer Network Distress
      Thermometer, Hospital Anxiety and Depression Scale, Multidimensional Scale of
      Perceived Social Support), measured presurgery, postintervention, 6 months, and 1
      year after surgery. RESULTS: Forty patients were included, 73% of whom completed
      rehabilitation. Results on emotional well-being ( P < .0001), global quality of
      life ( P = .0032), and mental health component score ( P = .0004) showed an
      overall statistically significant improvement during the study. CONCLUSION: This
      feasibility study demonstrated that global quality of life, mental health, and
      emotional well-being improved significantly during the study, from time of
      diagnosis until 1 year after resection, in patients with NSCLC participating in
      rehabilitation.

PMID- 27698262
TI  - Boehmenan, a Lignan From the Chinese Medicinal Plant Clematis armandii, Inhibits
      A431 Cell Growth via Blocking p70S6/S6 Kinase Pathway.
AB  - Previously, we have shown that boehmenan, a natural product isolated from the
      dried stem of Caulis clematidis armandii, exhibits various biological activities.
      The current study investigated the effects of boehmenan on the growth of human
      epidermoid carcinoma A431 cells. Cell viability and 50% inhibiting concentration
      (IC50) were assessed by CellTiter-Glo luminescent cell viability assay. Cell
      cycle arrest was measured by flow cytometry. Intracellular reactive oxygen
      species production and mitochondrial membrane potential (DeltaPsim) collapse were
      analyzed by a fluorescence spectrophotometer. The activation of epidermal growth
      factor receptor signaling pathway was evaluated by Western blot. The results
      showed that boehmenan significantly inhibited the growth of A431 cells (IC50 =
      1.6 uM) in a concentration- and time-dependent manner. This compound also blocked
      cell cycle progression at G2/M phase and modulated mitochondrial apoptosis
      related proteins, as evidenced by upregulating p21, cleaved caspase-3, and
      cleaved poly (ADP-ribose) polymerase protein levels and by downregulating Bcl-2,
      pro-caspase-9 levels. In addition, boehmenan also markedly induced intracellular
      reactive oxygen species production and DeltaPsim depolarization in a
      concentration-dependent manner. Furthermore, boehmenan-attenuated epidermal
      growth factor mediated the phosphorylation of signal transducer and activator of
      transcription 3 (STAT3), p70 ribosomal protein S6 kinase (p70S6)/S6 in a
      concentration-dependent manner. Taken together, our results suggest that
      boehmenan-mediated antiproliferative property in A431 cells was mediated
      partially by modulation of mitochondrial function and inhibition of STAT3 and
      p70S6 signal pathways.

PMID- 27698264
TI  - Antitumor Activity of the Chinese Medicine JC-001 Is Mediated by Immunomodulation
      in a Murine Model of Hepatocellular Carcinoma.
AB  - JC-001 is a Chinese medicine that has been used to treat liver disease; however,
      its significance in cancer treatment has not been characterized. In this study,
      we used an immunocompetent tumor model to characterize the antitumor activity of
      JC-001. A total of 48 Hepa 1-6 tumor-bearing C57BL/6 mice were randomly grouped
      into 4 groups and treated with H2O or JC-001 via oral administration. After
      hepatoma cell lines, including HepG2, Hep3B, SK-Hep-1, and Hepa 1-6, underwent 96
      hours of JC-001 treatment, a low cytotoxic effect was observed. In contrast, no
      direct cytotoxic effect of JC-001 on a normal human liver cell line, THLE-3, was
      observed under the same incubation conditions. Using a murine tumor model, we
      found that tumor growth could be inhibited by JC-001 in C57BL/6 mice but not in
      immunodeficient mice. Histopathological analysis of tumors from C57BL/6 mice
      revealed immune cell infiltration in tumors from the JC-001-treated group, as
      observed by hematoxylin and eosin staining; in addition, Ki67, hypoxia-inducible
      factor-1-alpha, and high mobility group box 1 expression levels were suppressed
      in the tumors. Both the coculture assay and murine spleen mRNA quantitative PCR
      analyses demonstrated that JC-001 could suppress Th17 immunity. Our data suggest
      that JC-001 is a Chinese medicine with low cytotoxicity that can significantly
      suppress tumor growth by immune regulation. This herbal remedy has great
      potential for future clinical application in hepatoma therapy.

PMID- 27698267
TI  - The future of dementia risk reduction research: barriers and solutions.
AB  - BACKGROUND: We examine why dementia prevention and risk reduction are relatively
      underfunded and suggest potential remediation strategies. The paper is aimed at
      researchers, funders and policy-makers, both within dementia and also the wider
      health prevention field. METHODS: A discussion-led workshop, attended by 58
      academics, clinicians, funders and policy-makers. RESULTS: The key barriers
      identified were the gaps in understanding the basic science of dementia; the
      complex interplay between individual risk factors; variations in study
      methodology; disincentives to collaboration; a lack of research capacity and
      leadership and the broader stigma of the condition. Recommendations were made to
      encourage strategic leadership, provide greater support for grant applications,
      promote collaboration and support randomized control trials for the research
      field. CONCLUSION: Having identified the barriers, the key challenge is how to
      implement the potential solutions. This will require engagement with decision
      makers within funding, policy and research to ensure that action takes place.

PMID- 27698265
TI  - Emodin Exerts an Antiapoptotic Effect on Human Chronic Myelocytic Leukemia K562
      Cell Lines by Targeting the PTEN/PI3K-AKT Signaling Pathway and Deleting BCR-ABL.
AB  - The BCR-ABL kinase inhibitor, imatinib mesylate, is the front-line treatment for
      chronic myeloid leukemia, but the emergence of imatinib resistance has led to the
      search for alternative drug treatments. There is a pressing need, therefore, to
      develop and test novel drugs. Natural products including plants, microorganisms,
      and halobios provide rich resources for discovery of anticancer drugs. In this
      article, we demonstrate that emodin inhibited the growth of K562 cells harboring
      BCR-ABL in vitro and in vivo, and induced abundant apoptosis, which was
      correlated with the inhibition of PETN/PI3K/Akt level and deletion of BCR-ABL.
      These findings suggest that emodin is a promising agent to kill K562 cells
      harboring BCR-ABL.

PMID- 27698266
TI  - Houttuynia cordata Thunb Promotes Activation of HIF-1A-FOXO3 and MEF2A Pathways
      to Induce Apoptosis in Human HepG2 Hepatocellular Carcinoma Cells.
AB  - Houttuynia cordata Thunb ( H cordata), a medicinal plant, has anticancer
      activity, as it inhibits cell growth and induces cell apoptosis in cancer.
      However, the potential anti-cancer activity and mechanism of H cordata for human
      liver cancer cells is not well understood. Recently, we identified hypoxia
      inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic
      factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute
      to the apoptosis of HepG2 hepatocellular carcinoma cells. FOXO3 transcription
      factors regulate target genes involved in apoptosis. H cordata significantly
      increased the mRNA and protein expression of HIF-1A and FOXO3 and stimulated
      MEF2A expression in addition to increased apoptosis in HepG2 cells within 24
      hours. Therefore, we determined the potential role of FOXO3 on apoptosis and on H
      cordata-induced MEF2A in HepG2 cells. HIF-1A silencing by siRNA attenuated MEF2A
      and H cordata-mediated FOXO3 upregulation in HepG2 cells. Furthermore, H cordata
      mediated MEF2A expression enhanced caspase-3 and caspase-7, which were abolished
      on silencing FOXO3 with siRNA. In addition, H cordata inhibited growth of human
      hepatocellular carcinoma xenografts in nude mice. Taken together, our results
      demonstrate that H cordata enhances HIF-1A/FOXO3 signaling, leading to MEF2A
      upregulation in HepG2 cells, and in parallel, it disturbs the expression of Bcl-2
      family proteins (Bax, Bcl-2, and Bcl-xL), which results in apoptosis. Taken
      together, these findings demonstrate that H cordata promotes the activation of
      HIF-1A-FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular
      carcinoma cells and is, therefore, a promising candidate for antitumor drug
      development.

PMID- 27698268
TI  - Characteristics of good supervision: a multi-perspective qualitative exploration
      of the Masters in Public Health dissertation.
AB  - Background: A dissertation is often a core component of the Masters in Public
      Health (MPH) qualification. This study aims to explore its purpose, from the
      perspective of both students and supervisors, and identify practices viewed as
      constituting good supervision. Methods: A multi-perspective qualitative study
      drawing on in-depth one-to-one interviews with MPH supervisors (n = 8) and
      students (n = 10), with data thematically analysed. Results: The MPH dissertation
      was viewed as providing generic as well as discipline-specific knowledge and
      skills. It provided an opportunity for in-depth study on a chosen topic but
      different perspectives were evident as to whether the project should be grounded
      in public health practice rather than academia. Good supervision practice was
      thought to require topic knowledge, generic supervision skills (including clear
      communication of expectations and timely feedback) and adaptation of supervision
      to meet student needs. Conclusions: Two ideal types of the MPH dissertation
      process were identified. Supervisor-led projects focus on achieving a clearly
      defined output based on a supervisor-identified research question and aspire to
      harmonize research and teaching practice, but often have a narrower focus.
      Student-led projects may facilitate greater learning opportunities and better
      develop skills for public health practice but could be at greater risk of course
      failure.

PMID- 27698269
TI  - Community pharmacists' evaluation of potentially inappropriate prescribing in
      older community-dwelling patients with polypharmacy: observational research based
      on the GheOP3S tool.
AB  - Background: In this study, we aimed to (i) determine the prevalence of
      potentially inappropriate prescribing (PIP) in community-dwelling older
      polypharmacy patients using the Ghent Older People's Prescriptions community
      Pharmacy Screening (GheOP3S) tool, (ii) identify the items that account for the
      highest proportion of PIP and (iii) identify the patient variables that may
      influence the occurrence of PIP. Additionally, pharmacist-physician contacts
      emerging from PIP screening with the GheOP3S tool and feasibility of the GheOP3S
      tool in daily practice were evaluated. Methods: A prospective observational study
      was carried out between December 2013 and July 2014 in 204 community pharmacies
      in Belgium. Patients were eligible if they were (i) >=70 years, (ii) community
      dwelling, (iii) using >=5 chronic drugs, (iv) a regular visitor of the pharmacy
      and (v) understanding Dutch or French. Community pharmacists used a structured
      interview to obtain demographic data and medication use and subsequently screened
      for PIP using the GheOP3S tool. A Poisson regression was used to investigate the
      association between different covariates and the number of PIP. Results: In 987
      (97%) of 1016 included patients, 3721 PIP items were detected (median of 3 per
      patient; inter quartile range: 2-5). Most frequently involved with PIP are drugs
      for the central nervous system such as hypnosedatives, antipsychotics and
      antidepressants. Risk factors for a higher PIP prevalence appeared to be a higher
      number of drugs (30% extra PIPs per 5 extra drugs), female gender (20% extra
      PIPs), higher body mass index (BMI, 20% extra PIPs per 10-unit increase in BMI)
      and poorer functional status (30% extra PIPs with 6-point increase). The
      feasibility of the GheOP3S tool was acceptable although digitalization of the
      tool would improve implementation. Despite detecting at least one PIP in 987
      patients, only 39 physicians were contacted by the community pharmacists to
      discuss the items. Conclusion: A high prevalence of PIP in community-dwelling
      older polypharmacy patients in Belgium was detected which urges for interventions
      to reduce PIP.

PMID- 27698270
TI  - Onchocerciasis Elimination from Africa: One Step in Northern Sudan.

PMID- 27698271
TI  - Pediatric Visceral Leishmaniasis Caused by Leishmania infantum in Northern
      Cyprus.
AB  - Visceral leishmaniasis (VL) is a vector-borne disease widespread in the
      Mediterranean basin, including Cyprus. During the last decades no cases were
      notified from northern Cyprus, but herein three cases of VL (female: 2, male: 1,
      median age: 24.6 months) diagnosed during their hospital admission between
      January 2011 and December 2012 are reported. Diagnosis was based on clinical
      findings; 1 >= 1/64 titer positivity of immunofluorescence antibodies, Leishmania
      amastigotes in Giemsa-stained slides of bone marrow, as well as molecular
      identification confirmed that in all three the infecting pathogen was Leishmania
      infantum Fever, splenomegaly, and hepatomegaly were the typical clinical
      findings. First-line treatment with liposomal amphotericin B (AmBisome(r);
      intravenous, 3 mg/kg) on days 1-5, followed by the same on days 10 and 21 yielded
      a successful outcome with no relapse in all cases. These confirmed VL cases found
      within 2 years demonstrate the presence of VL on the island.

PMID- 27698272
TI  - Observed Handwashing with Soap Practices Among Cholera Patients and Accompanying
      Household Members in a Hospital Setting (CHoBI7 Trial).
AB  - Household members of cholera patients are at a 100 times higher risk of cholera
      than the general population. Despite this risk, there are only a handful of
      studies that have investigated the handwashing practices among hospitalized
      diarrhea patients and their accompanying household members. To investigate
      handwashing practices in a hospital setting among this high-risk population, 444
      hours of structured observation was conducted in a hospital in Dhaka, Bangladesh,
      among 148 cholera patients and their household members. Handwashing with soap
      practices were observed at the following key events: after toileting, after
      cleaning the anus of a child, after removing child feces, during food
      preparation, before eating, and before feeding. Spot-checks were also conducted
      to observe the presence of soap at bathroom areas. Overall, 4% (4/103) of key
      events involved handwashing with soap among cholera patients and household
      members during the structured observation period. This was 3% (1/37) among
      cholera patients and 5% (3/66) for household members. For toileting events,
      observed handwashing with soap was 7% (3/46) overall, 7% (1/14) for cholera
      patients, and 6% (2/32) for household members. For food-related events, overall
      observed handwashing with soap was 2% (2/93 overall), and 0% (0/34) and 3% (2/59)
      for cholera patients and household members, respectively. Soap was observed at
      only 7% (4/55) of handwashing stations used by patients and household members
      during spot-checks. Observed handwashing with soap at key times among patients
      and accompanying household members was very low. These findings highlight the
      urgent need for interventions to target this high-risk population.

PMID- 27698273
TI  - Chlorination of Household Drinking Water Among Cholera Patients' Households to
      Prevent Transmission of Toxigenic Vibrio cholerae in Dhaka, Bangladesh: CHoBI7
      Trial.
AB  - Household members of cholera patients are at a 100 times higher risk of cholera
      infections than the general population because of shared contaminated drinking
      water sources and secondary transmission through poor household hygiene
      practices. In this study, we investigated the bactericidal concentration of free
      chlorine required to inactivate Vibrio cholerae in household drinking water in
      Dhaka, Bangladesh. In laboratory experiments, we found that the concentrations of
      free chlorine required to inactivate 105 colony-forming units (CFU)/mL of V.
      cholerae serogroups O1 and O139 were 0.1 mg/L and 0.2 mg/L, respectively. The
      concentration of free chlorine generated by a single chlorine tablet (sodium
      dichloroisocyanurate [33 mg]) after a 30-minute reaction time in a 10-L sealed
      vessel containing Dhaka city municipal supply water was 1.8 mg/L; and the
      concentration declined to 0.26 mg/L after 24 hours. In field measurements, water
      collected from 165 households enrolled in a randomized controlled trial (RCT) of
      a chlorine and handwashing with soap intervention (Cholera-Hospital-Based
      Intervention-for-7-Days [CHoBI7]), we observed significantly higher free chlorine
      concentrations in the 82 intervention arm households (mean = 1.12 mg/L, standard
      deviation [SD] = 0.52, range = 0.07-2.6 mg/L) compared with the 83 control
      households (0.017 mg/L, SD = 0.01, range = 0-0.06 mg/L) (P < 0.001) during spot
      check visits. These findings suggest that point-of-use chlorine tablets present
      an effective approach to inactivate V. cholerae from drinking water in households
      of cholera patients in Dhaka city. This result is consistent with the findings
      from the RCT of CHoBI7 which found that this intervention led to a significant
      reduction in symptomatic cholera infections among household members of cholera
      patients and no stored drinking water samples with detectable V. cholerae.

PMID- 27698274
TI  - Geophagy in Northern Uganda: Perspectives from Consumers and Clinicians.
AB  - The etiology and health consequences of geophagy are still poorly understood. The
      consumed soil, individual motives, consumption habits, and the clinical
      perspective of geophagy in northern Uganda were examined. A total of 50
      semistructured interviews (17 pregnant, eight nonpregnant women, 10 men, and 15
      health-care professionals) were conducted. Our results suggest that geophagy is
      not limited to pregnancy and can also be found among nonpregnant women and men.
      During gestation, excessive amounts of various soil types are consumed and can
      replace food at times. Nonpregnant women and men consume less soil and stick to
      one type. When pregnant, craving and alleviating gastrointestinal upset are the
      main motives. In men, the main reasons for geophagy were craving,
      hypersalivation, and natural stimulants. If soil is craved, it can show
      similarities to a dependency syndrome. When picked up in childhood, geophagy is
      more likely to be continued throughout life. The consumption habits differ and
      thereby vary in their possible implications on health. Our findings suggest that
      men should be included in further studies. Especially nurses from the antenatal
      care are exposed to geophagists; however, no national guidelines exist for
      geophagy. Further research is necessary to create guidelines to be included in
      medical training and practice.

PMID- 27698275
TI  - Spontaneous Splenic Rupture Caused by Scrub Typhus.
AB  - Spontaneous rupture of the spleen is rarely described as a complication of scrub
      typhus infection. We report a previously healthy 74-year-old Thai female farmer
      who presented in Nakhon Ratchasima, Thailand, with a history of fever and malaise
      for 5 days, followed by abdominal pain for 1 day. An exploratory laparotomy was
      performed due to peritonitis. Operative findings revealed a ruptured spleen and
      hemoperitoneum. A splenectomy was performed afterward. Scrub typhus was confirmed
      by a 4-fold increase of IgM titer using an indirect immunofluorescence antibody
      assay and a positive result from the polymerase chain reaction targeting the 47-
      and 56-kDa genes in Orientia tsutsugamushi She responded well to intravenous
      chloramphenicol and defervesced within 24 hours without any complication.

PMID- 27698276
TI  - Human Toxocariasis: Prevalence and Factors Associated with Biosafety in Research
      Laboratories.
AB  - Human toxocariasis is a neglected parasitic disease worldwide. Researchers
      studying this disease use infectious strains of Toxocara for experiments. Health
      workers are at risk in the course of their daily routine and must adhere to
      biosafety standards while carrying out the activities. Researchers on biosafety
      concerning working with these parasites are insufficient. The aim of this study
      was to determine the rate of seroprevalence of Toxocara species among health-care
      research laboratory workers (professors, technicians, and students), and to
      investigate the risk factors of Toxocara infection associated with laboratory
      practices. This cross-sectional study involved 74 researchers at two federal
      universities in southern Brazil from February 2014 to February 2015; 29
      researchers manipulated infective strains of Toxocara canis (test group) and 45
      did not (control group). Serum samples were examined using enzyme-linked
      immunosorbent assay. Epidemiological data were obtained via a questionnaire
      containing information about laboratory routine, eating behavior, and contact
      with dogs. The seroprevalence of anti-T. canis IgG was 14.9% (11/74; 13.8% [4/29]
      in the test group and 15.6% [7/45] in the control group). Most individuals in the
      test group correctly understood the primary mode of infection; however, 13.8% did
      not use gloves while manipulating T. canis eggs. Knowledge of biosafety must be
      well understood by health-care professionals doing laboratory work with
      biological agents. To our knowledge, this is the first study to investigate the
      rate of seroprevalence of IgG against Toxocara spp. among professionals and
      students who handle infective forms of the nematode T. canis.

PMID- 27698278
TI  - Lessons learnt by IRSN about the involvement of experts towards the population in
      contaminated areas in Fukushima Prefecture.
AB  - Since November 2011, Institut de radioprotection et de surete nucleaire (IRSN)
      experts have participated in the International Commission on Radiological
      Protection's (ICRP) dialogue initiative for the rehabilitation of living
      conditions after the Fukushima accident. In 2013, IRSN and Centre d'etude sur
      l'Evaluation de la Protection dans le domaine Nucleaire (CEPN) launched a study
      to identify the main lessons that can be learned from these dialogues, and
      benefit French IRSN experts in the event of a postaccident situation. The main
      lesson is that in order to protect the inhabitants of contaminated areas
      efficiently, experts must work in cooperation with local actors to develop a co
      expertise process. The availability of measurement devices for inhabitants is
      crucial to allow them to assess their own radiological situation. Measuring
      radioactivity makes it visible, and allows individuals to discuss the results in
      their communities and develop local projects to improve their daily life.
      Eventually, inhabitants create a practical radiological protection culture to
      manage their situation. However, helping people to protect themselves does not
      mean that authorities and experts have no responsibilities, and this calls for
      strong ethical principles such as not making decisions for people about their
      future. To be helpful, scientists need to understand that, as necessary as
      radiation protection is, it is not the only problem that inhabitants are facing
      and it cannot control people's lives. Radiation protection experts must commit
      themselves to be at the service of individuals and the community, and the issues
      they want to address.

PMID- 27698277
TI  - Community-Based Surveillance to Monitor Mortality in a Malaria-Endemic and Ebola
      Epidemic Setting in Rural Guinea.
AB  - Multiple community-based approaches can aid in quantifying mortality in the
      absence of reliable health facility data. Community-based sentinel site
      surveillance that was used to document mortality and the systems utility for
      outbreak detection was evaluated. We retrospectively analyzed data from 46
      sentinel sites in three sous-prefectures with a reinforced malaria control
      program and one sous-prefecture without (Koundou) in Guinea. Deaths were recorded
      by key informants and classified as due to malaria or another cause. Malaria
      deaths were those reported as due to malaria or fever in the 3 days before death
      with no other known cause. Suspect Ebola virus disease (sEVD) deaths were those
      due to select symptoms in the EVD case definition. Deaths were aggregated by sous
      prefecture and analyzed by a 6-month period. A total of 43,000 individuals were
      monitored by the surveillance system; 1,242 deaths were reported from July 2011
      June 2014, of which 55.2% (N = 686) were reported as due to malaria. Malaria
      attributable proportional mortality decreased by 26.5% (95% confidence interval
      [CI] = 13.9-33.1, P < 0.001) in the program area and by 6.6% (95% CI = -17.3
      30.5, P = 0.589) in Koundou. Sixty-eight deaths were classified as sEVD and
      increased by 6.1% (95% CI = 1.3-10.8, P = 0.021). Seventeen sEVD deaths were
      reported from November 2013 to March 2014 including the first two laboratory
      confirmed EVD deaths. Community surveillance can capture information on mortality
      in areas where data collection is weak, but determining causes of death remains
      challenging. It can also be useful for outbreak detection if timeliness of data
      collection and reporting facilitate real-time data analysis.

PMID- 27698279
TI  - Looking back on media reports on the nuclear accident.
AB  - The accident at Fukushima Daiichi nuclear power plant in the wake of the Great
      East Japan Earthquake received considerable media coverage. However, a leaning
      towards sensationalism and a proclivity for denouncing those in power resulted in
      articles that were, in several instances, scientifically inaccurate, causing
      anxiety among disaster victims and delaying recovery efforts. Individuals working
      for the local media in Fukushima had the task of reporting the disaster while
      being victims of the disaster at the same time. Therefore, many individuals
      studied and deepened their knowledge about radiation and its effects, and were
      pained to see inaccurate media coverage of the disaster. Should they have been
      more forthright in opposing such false media coverage?

PMID- 27698280
TI  - CT-angiography source images indicate less fatal outcome despite coma of patients
      in the Basilar Artery International Cooperation Study.
AB  - Background Coma is associated with poor outcome in patients with basilar artery
      occlusion. Aims We sought to assess whether the posterior circulation Acute
      Stroke Prognosis Early CT Score and the Pons-Midbrain Index applied to CT
      angiography source images predict the outcome of comatose patients in the Basilar
      Artery International Cooperation Study. Methods Basilar Artery International
      Cooperation Study was a prospective, observational registry of patients with
      acute basilar artery occlusion with 48 recruiting centers worldwide. We applied
      posterior circulation Acute Stroke Prognosis Early CT Score and Pons-Midbrain
      Index to CT angiography source images of Basilar Artery International Cooperation
      Study patients who presented with coma. We calculated adjusted risk ratios to
      assess the association of dichotomized posterior circulation Acute Stroke
      Prognosis Early CT Score (>=8 vs. <8) and Pons-Midbrain Index (<3 vs. >=3) with
      mortality and favourable outcome (modified Rankin Scale score 0-3) at one month.
      Results Of 619 patients in the Basilar Artery International Cooperation Study
      registry, CT angiography source images were available for review in 158 patients.
      Among these, 78 patients (49%) presented with coma. Compared to non-comatose
      patients, comatose patients were more likely to die (risk ratios 2.34; CI 95%
      1.56-3.52) and less likely to have a favourable outcome (risk ratios 0.44; CI 95%
      0.24-0.80). Among comatose patients, a Pons-Midbrain Index < 3 was related to
      reduced mortality (adjusted RR 0.66; 95% CI 0.46-0.96), but not to favourable
      outcome (adjusted RR 1.19; 95% CI 0.39-3.62). Posterior circulation Acute Stroke
      Prognosis Early CT Score dichotomized at >= 8 vs. <8 was not significantly
      associated with death (adjusted RR 0.70; 95% CI 0.46-1.05). Conclusion In
      comatose patients with basilar artery occlusion, the extent of brainstem ischemia
      appears to be related to mortality but not to favourable outcome.

PMID- 27698283
TI  - Corrigendum.
AB  - Corrigendum to Season of birth and not vitamin D receptor promoter polymorphisms
      is a risk factor for multiple sclerosis by DA Fernandes de Abreu, MC Babron I, C
      Rebeix, J Fontenille, D Yaouanq, B Brassat, F Fontaine, F Clerget-Darpoux, F
      Jehan and Feron. Mult Scler 2009; 15: 1146-1152 [DOI: 10.1177/1352458509106780].

PMID- 27698281
TI  - Why do transient ischemic attack patients have higher early stroke recurrence
      risk than those with ischemic stroke? Influence of patient behavior and other
      risk factors in the North Dublin Population Stroke Study.
AB  - Background Few studies have directly compared stroke recurrence rates after
      stroke and transient ischemic attack, and the risk factors underlying early
      recurrence are poorly understood. We aimed to investigate risk factors for
      recurrent stroke after first stroke and transient ischemic attack in a population
      based study. Methods The North Dublin Population Stroke Study applied multiple
      overlapping hot and cold pursuit methods, to ascertain hospital- and community
      treated stroke and transient ischemic attack patients over a 12-month period.
      Inclusion criteria were: (1) Stroke-physician confirmed transient ischemic
      attack/ischemic stroke; (2) first-stroke/transient ischemic attack event within
      the ascertainment period. Patients were prospectively followed at 72 h, 7, 28 and
      90 days. Results A total of 584 patients met eligibility criteria (172 transient
      ischemic attack, 412 stroke). More transient ischemic attack than stroke patients
      presented to medical attention with recurrent stroke (8.24% vs. 0.24%, p =
      0.0002). Recurrent stroke was more common after transient ischemic attack than
      index stroke at each time-interval (at 72 h, 4.07% vs. 1.23%, p = 0.03; at 90
      days, 13.45% vs. 5.72%, p = 0.002). Stroke recurrence at 90 days was also
      associated with delay seeking medical attention after the index event (OR 3.2, p
      = 0.001), delayed anti-platelet (OR 2.8, p = 0.001) and statin (OR 2.4, p =
      0.009) treatment, carotid stenosis/occlusion (OR 2.4, p = 0.008). On
      multivariable analysis, transient ischemic attack as index event (adjusted OR
      2.3, p = 0.02), delayed statin treatment (OR 2.5, p = 0.02), and carotid
      stenosis/occlusion (OR 2.4, p = 0.02) were independent predictors of 90-day
      recurrent stroke. Conclusion A combination of pathophysiological and behavioral
      factors was associated with early stroke recurrence risk. Improved public
      awareness to reduce delays to self-referral for transient ischemic attack
      symptoms is needed.

PMID- 27698285
TI  - Highly reproducible surface-enhanced Raman scattering substrate for detection of
      phenolic pollutants.
AB  - The ordering degree of nanostructures is the key to determining the uniformity of
      surface-enhanced Raman scattering (SERS). However, fabrication of large-area
      ordered nanostructures remains a challenge, especially with the ultrahigh-density
      (>1010 cm-2). Here, we report a fabrication of large-area ultrahigh-density
      ordered Ag@Al2O3/Ag core-shell nanosphere (NS) arrays with tunable
      nanostructures. The ultrahigh-density (2.8 * 1010 cm-2) ordered NS arrays over a
      large-area capability (diameter >4.0 cm) enable the uniform SERS signals with the
      relative standard deviation of less than 5%. The as-fabricated highly
      reproducible SERS substrate can be applied to detect trace phenolic pollutants in
      water. This work does not only provide a new route for synthesizing the ultrahigh
      density ordered nanostructures, but also create a new class of SERS substrates
      with high sensitivity and excellent reproducibility.

PMID- 27698284
TI  - Far from the Madding Crowd: the Molecular Basis for Immunological Escape of
      Plasmodium falciparum.
AB  - Like Thomas Hardy's famous novel Far from the Madding Crowd, Plasmodium
      falciparum parasites display their most relevant survival structures (proteins)
      involved in host cell invasion far away from the immune system's susceptible
      regions, displaying tremendous genetic variability, to attract the immune
      response and escape immune pressure. The 3D structure localisation of the
      conserved amino acid sequences of this deadly parasite's most relevant proteins
      involved in host cell invasion, as well as the location of the highly
      polymorphic, highly immunogenic regions, clearly demonstrates that such
      structures are far apart, sometimes 90 degrees  to 180 degrees  opposite, thereby
      rendering the immune response useless. It is also shown here that these
      conserved, functionally-relevant structures are immunologically silent, since no
      immune response has been induce.

PMID- 27698286
TI  - Experimental and theoretical rationalization of the growth mechanism of silicon
      quantum dots in non-stoichiometric SiN x : role of chlorine in plasma enhanced
      chemical vapour deposition.
AB  - Silicon quantum dots (Si-QDs) embedded in an insulator matrix are important from
      a technological and application point of view. Thus, being able to synthesize
      them in situ during the matrix growth process is technologically advantageous.
      The use of SiH2Cl2 as the silicon precursor in the plasma enhanced chemical
      vapour deposition (PECVD) process allows us to obtain Si-QDs without post-thermal
      annealing. Foremost in this work, is a theoretical rationalization of the
      mechanism responsible for Si-QD generation in a film including an analysis of the
      energy released by the extraction of HCl and the insertion of silylene species
      into the terminal surface bonds. From the results obtained using density
      functional theory (DFT), we propose an explanation of the mechanism responsible
      for the formation of Si-QDs in non-stoichiometric SiN x starting from chlorinated
      precursors in a PECVD system. Micrograph images obtained through transmission
      electron microscopy confirmed the presence of Si-QDs, even in nitrogen-rich (N
      rich) samples. The film stoichiometry was controlled by varying the growth
      parameters, in particular the NH3/SiH2Cl2 ratio and hydrogen dilution.
      Experimental and theoretical results together show that using a PECVD system,
      along with chlorinated precursors it is possible to obtain Si-QDs at a low
      substrate temperature without annealing treatment. The optical property studies
      carried out in the present work highlight the prospects of these thin films for
      down shifting and as an antireflection coating in silicon solar cells.

PMID- 27698287
TI  - Molecular beam epitaxy of InAs nanowires in SiO2 nanotube templates: challenges
      and prospects for integration of III-Vs on Si.
AB  - Guided growth of semiconductor nanowires in nanotube templates has been
      considered as a potential platform for reproducible integration of III-Vs on
      silicon or other mismatched substrates. Herein, we report on the challenges and
      prospects of molecular beam epitaxy of InAs nanowires in SiO2/Si nanotube
      templates. We show how and under which conditions the nanowire growth is
      initiated by In-assisted vapor-liquid-solid growth enabled by the local
      conditions inside the nanotube template. The conditions for high yield of
      vertical nanowires are investigated in terms of the nanotube depth, diameter and
      V/III flux ratios. We present a model that further substantiates our findings.
      This work opens new perspectives for monolithic integration of III-Vs on the
      silicon platform enabling new applications in the electronics, optoelectronics
      and energy harvesting arena.

PMID- 27698288
TI  - Assent, consent and paediatric bioethics. Commentary.
AB  - In the ethics of relations between physicians and paediatric patients the
      question of autonomy and its corollary, consent, is crucial. While the importance
      attached to autonomy in the clinical setting is not the same as that accorded in
      research, it nonetheless assumes greater relevance when minors are involved, and
      a careful case-by-case assessment becomes obligatory.

PMID- 27698289
TI  - Monitoring and managing mental health in the wake of Ebola. Commentary.
AB  - Infectious disease continues to have dramatic effects on morbidity and mortality
      around the world. Few events could cause such loss of life and damage to
      livelihoods. As witnessed with the recent West African Ebola outbreak, raising
      alerts and identifying the outbreak in the community took too long. As a
      consequence local health systems were quickly overwhelmed. In addition, response
      at the international level proved slow and poorly coordinated. Rapid diagnostics,
      effective therapeutics, protective equipment, and a vaccine were all lacking. The
      crisis was however ultimately halted, thanks to a massive deployment of
      international resources in combination with the bravery and compassion of the
      medical staff, scientists, healthcare and aid workers on the ground. Despite this
      triumph, the lingering psychological sequalae of Ebola remain a significant
      public health challenge. The importance of mental health service delivery and
      policy implementation in addition to public health funding resources will prove
      integral in tackling this issue in the long run. With this in mind, adopting a
      political ecology approach towards health and disease will be crucial in order to
      depathologize the clinically significant mental distress related to Ebola.

PMID- 27698290
TI  - Climate change and occupational health. Preface.

PMID- 27698292
TI  - Climate change impact on microclimate of work environment related to occupational
      health and productivity.
AB  - INTRODUCTION: Climate change is a global emergency that influences human health
      and occupational safety. Global warming characterized by an increase in
      temperature of the ambience and humidity affects human health directly impairing
      body thermoregulation with serious consequences: dehydration, fatigue, heat
      stroke and even death. Several studies have demonstrated negative effects of
      climate change on working populations in a wide variety of workplaces with
      particular regard to outdoor and uncooled indoor workplaces. Most vulnerable
      workers are outdoor workers in tropical and subtropical countries usually
      involved in heavy labor during hot seasons. Many of the consequences therefore,
      regarding working people are possible, even without health symptoms by reducing
      work productivity. AIM: The scope of this review is to investigate effects of
      climate change on workers both in relation to health and work productivity.
      METHODS: This study has been realized by analyzing recent international
      literature. CONCLUSIONS: In order to reduce negative effects of climate change on
      working populations it is essential to implement preventive measures with a
      multidisciplinary strategy limiting health risks and improving work productivity.

PMID- 27698291
TI  - Global and Mediterranean climate change: a short summary.
AB  - : Observed changes at the global scale. An increase of the annual mean global
      temperature and changes of other climate parameters have been observed in the
      last century. The global temperature and the atmospheric concentration of
      greenhouse gases are changing at a very fast pace compared to those found in
      palaeoclimate records. Changes in the Mediterranean. Variations of some climate
      change indicators can be much larger at the local than at the global scale, and
      the Mediterranean has been indicated among the regions most sensitive to climate
      change, also due to the increasing anthropogenic pressure. Model projections for
      the Mediterranean foresee further warming, droughts, and long-lasting
      modifications. IMPACTS: Regional climate changes impact health and ecosystems,
      creating new risks, determined not only by weather events, but also by changing
      exposures and vulnerabilities. These issues, and in particular those regarding
      occupational safety, have not been sufficiently addressed to date.

PMID- 27698293
TI  - Impact of climate change on occupational exposure to solar radiation.
AB  - Occupational exposure to solar radiation may induce both acute and long-term
      effects on skin and eyes. Personal exposure is very difficult to assess
      accurately, as it depends on environmental, organisational and individual
      factors. The ongoing climate change interacting with stratospheric ozone dynamics
      may affect occupational exposure to solar radiation. In addition, tropospheric
      levels of environmental pollutants interacting with solar radiation may be
      altered by climate dynamics, so introducing another variable affecting the
      overall exposure to solar radiation. Given the uncertainties regarding the
      direction of changes in exposure to solar radiation due to climate change,
      compliance of outdoor workers with protective measures and a proper health
      surveillance are crucial. At the same time, education and training, along with
      the promotion of healthier lifestyles, are of paramount importance.

PMID- 27698294
TI  - The association between extreme weather conditions and work-related injuries and
      diseases. A systematic review of epidemiological studies.
AB  - INTRODUCTION: The relationship between extreme temperature and population health
      has been well documented. Our objective was to assess the evidence supporting an
      association between extreme temperature and work related injuries. METHODS: We
      carried out a systematic search with no date limits using PubMed, the Cochrane
      central register of controlled trials, EMBASE, Web of Science and the internet
      sites of key organizations on environmental and occupational health and safety.
      Risk of bias was evaluated with Cochrane procedure. RESULTS: Among 270 studies
      selected at the first step, we analyzed 20 studies according to inclusion
      criteria (4 and 16 referring to extreme cold and heat temperature, respectively).
      DISCUSSION: Despite the relevance for policy makers and for occupational safety
      authorities, the associations between extreme temperature and work related
      injuries is seldom analyzed. The estimation of risk, the identification of
      specific jobs involved and the characterization of the complex mechanisms
      involved could help to define prevention measures.

PMID- 27698295
TI  - Climate change and agricultural workers' health in Ecuador: occupational exposure
      to UV radiation and hot environments.
AB  - Climate change is a global concern but little is known about its potential health
      effects in workers from non-industrialized countries. Ecuadorian workers from the
      coast (hot environments) and Andean region (elevated UV radiation) might be at
      particular risk of such effects. In the Andean region, measurements of UV index
      show maximum levels exceeding 11, a level considered being extreme according to
      the WHO. Also, an increased incidence of skin cancer was reported the last
      decennium, this being the second most common cancer type in men and women. In the
      coast, a high reported prevalence of kidney disease in agricultural workers is
      suggested to be related to exposure to hot temperatures. The scarce data
      available on occupational health in Ecuadorian agricultural workers raise the
      need for further investigation. Data worldwide shows an increasing prevalence of
      UV radiation- and heat stress-related illnesses in agricultural workers and urges
      the adoption of preventive measures.

PMID- 27698296
TI  - Climate change: the potential impact on occupational exposure to pesticides.
AB  - OBJECTIVE: This study investigates the possible influence of global climate
      change (GCC) on exposure to plant protection products (PPP) in the workplace.
      METHODS: The paper has evaluated the main potential relationships between GCC and
      occupational exposure to pesticides, by highlighting how global warming might
      affect their future use and by reviewing its possible consequence on workers'
      exposure. RESULTS: Global warming, influencing the spatial and temporal
      distribution and proliferation of weeds, the impact of already present insect
      pests and pathogens and the introduction of new infesting species, could cause a
      changed use of pesticides in terms of higher amounts, doses and types of products
      applied, so influencing the human exposure to them during agricultural
      activities. GCC, in particular heat waves, may also potentially have impact on
      workers' susceptibility to pesticides absorption. CONCLUSIONS: Prevention
      policies of health in the workplace must be ready to address new risks from
      occupational exposure to pesticide, presumably different from current risks,
      since an increased use may be expected.

PMID- 27698297
TI  - Climate change and safety at work with ionizing radiations.
AB  - The accident at Tokyo Electric Power Company's (TEPCO's) Fukushima Daiichi
      nuclear power plant (NPP) has been one of the dominant topic in nuclear safety
      and it has brought new attention on the matter of accidents in NPPs due to
      external events related to natural causes. Climate change has risen new risks and
      the growing probability of extreme external events has increased exposure and
      vulnerability of workers in the nuclear sector. However extreme natural events
      are a threat not only to NPPs but to all facilities dealing with radioactive
      material and in an emergency scenario they can affect the effectiveness and
      implementation of safety devices and procedures and also prevent communications,
      causing delays in the readiness of response. It is clear that adaptation
      strategies are necessary to cope with emerging changes in climate and a new
      nuclear safety culture is growing, that addresses accidents initiated not only by
      internal but also by external events.

PMID- 27698299
TI  - Climate change and occupational allergies: an overview on biological pollution,
      exposure and prevention.
AB  - INTRODUCTION: Climate change, air pollution, temperature increase and other
      environmental variables are modifying air quality, contributing to the increase
      of prevalence of allergic respiratory diseases. Allergies are complex diseases
      characterized by multilevel interactions between individual susceptibility,
      response to immune modulation and environmental exposures to physical, chemical
      and biological agents. Occupational allergies introduce a further complexity to
      these relationships by adding occupational exposure to both the indoor and
      outdoor ones in the living environment. OBJECTIVE: The aim of this paper is to
      overview climate-related allergy affecting environmental and occupational health,
      as literature data are scanty in this regard, and to suggest a management model
      of this risk based on a multidisciplinary approach, taking the case of biological
      pollution, with details on exposure and prevention. CONCLUSIONS: The management
      of climate-related occupational allergy should take into account preventive
      health strategies, environmental, public and occupational interventions, as well
      as to develop, implement, evaluate, and improve guidelines and standards
      protecting workers health under changing climatic conditions; new tools and
      strategies based on local conditions will have to be developed. Experimental
      studies and acquisition of environmental and personal data have to be matched to
      derive useful information for the scope of occupational health and safety.

PMID- 27698298
TI  - Climate change, vector-borne diseases and working population.
AB  - INTRODUCTION: Risks associated with climate change are increasing worldwide and
      the global effects include altered weather and precipitation patterns, rising
      temperatures and others; human health can be affected directly and indirectly.
      This paper is an overview of literature regarding climate changes, their
      interaction with vector-borne diseases and impact on working population.
      MATERIALS AND METHODS: Articles regarding climate changes as drivers of vector
      borne diseases and evidences of occupational cases have been picked up by public
      databank. Technical documents were also included in the study. RESULTS: Evidences
      regarding the impact of climate changes on vector-borne diseases in Europe,
      provided by the analysis of the literature, are presented. DISCUSSION: Climate
      sensitive vector-borne diseases are likely to be emerging due to climate
      modifications, with impacts on public and occupational health. However, other
      environmental and anthropogenic drivers such as increasing travelling and trade,
      deforestation and reforestation, altered land use and urbanization can influence
      their spread. Further studies are necessary to better understand the phenomenon
      and implementation of adaptation strategies to protect human health should be
      accelerated and strengthened.

PMID- 27698300
TI  - Towards a greener labour market: occupational health and safety implications.
AB  - BACKGROUND: Climate change and environmental degradation are seriously
      jeopardizing the future environmental and economic sustainability at the global
      level prompting urgent calls for a shift towards more sustainable development and
      greener economies. The use of the so called green jobs is a key strategy to
      overcome economic and ecological crisis. AIM: The present study discusses the
      implications for employment and decent work of green jobs in order to identify
      information/training measures to enhance skills of employees protecting their
      working conditions. RESULTS: Despite all the emphasis laid today on the green
      economy, occupational health and safety (OHS) issues have still been talked only
      limited, as already noted in previous studies and literature reviews. CONCLUSION:
      It is needed to assess traditional and new OHS risks within green jobs in order
      to facilitate the transfer of OHS knowledge to green technologies as well as
      identifying OHS training needs.

PMID- 27698301
TI  - Quality of life in refugees and asylum seekers in Italy: a pilot study.
AB  - Interest in measuring the Health Related Quality of Life (HRQoL) of the
      immigrants increased in recent years in Italy as in other countries. Our purpose
      was to evaluate the HRQoL of refugees welcomed in Tuscany using the SF-36
      questionnaire. We collected 114 questionnaires from 2011 to 2015. Our samples was
      constituted by 98 males and 16 females, coming from different regions of the
      world; the mean age was 27.4. Statistical analysis showed that gender, length of
      stay and educational qualification are not associated with a poorer HRQoL.
      Instead, elderly refugees showed lower scores; refugees from African region
      reported a better HRQoL than the others, and there are also differences between
      refugees welcomed in different cities of Tuscany. Our purpose is to continue this
      study enlarging the sample size and the geographical coverage, in order to have a
      more interesting description of the health perception of refugees welcomed in
      Italy.

PMID- 27698302
TI  - Parent training education program: a pilot study, involving families of children
      with Prader-Willi syndrome.
AB  - INTRODUCTION: Prader-Willi syndrome (PWS) is a rare genetic disorder
      characterized by severe hypotonia during the neonatal period and the first two
      years of life, the onset of hyperphagia with a risk of obesity during infancy and
      adulthood, learning difficulties and behavioral or severe psychiatric problems.
      This complex disease has severe consequences and difficult management issues also
      for patients' families. Parents of children with PWS need appropriate
      psychoeducational intervention in order to better manage their children with PWS.
      The purpose of this study was the implementation and evaluation of a PWS
      psychoeducational parent training program. METHODS: The Italian National Center
      for Rare Diseases implemented a pilot parent training program offered to parents
      of children with PWS. The intervention's effects was evaluated using
      questionnaires comprised of 11 items rated on a 7 point Likert scale. RESULTS:
      The intervention was offered to 43 parents. The behavior problems management,
      dietary restrictions, autonomy and relationships were indicated by parents as the
      priority topics which needed to be addressed. Evaluations, immediately post
      intervention and after 6 months, were reported by parents, fulfilling specific
      questionnaires. 90% of parents involved in the study, appreciated the
      methodology, 86% felt more informed about PWS, 47-62% felt more capable to better
      approach behaviour's problems, 20-25% felt better about the child's health
      situation and future expectations. Feeling more capable to help the child
      autonomy and relationships were reported in 62% and 63% of parents respectively,
      which decreased significantly (p < 0.05) according to the evaluation 6 months
      after the intervention. Younger age of parents (< 44 years of age) was
      significantly correlated with better understanding on how to help the child's
      autonomy (OR: 0.05; CI: 0.04-0.8) and to better collaborate with the child's
      teachers (OR: 0.02; CI: 0.001-0.9). CONCLUSION: Parent training is a promising
      intervention for parents of children with behavior's problems. Interventions with
      a behaviorally oriented program, addressed to parents of PWS affected children,
      is a useful tool in increasing their ability to manage the problems related to
      the disease.

PMID- 27698303
TI  - Telemedicine in palliative care: a review of systematic reviews.
AB  - AIMS: To evaluate the quality of systematic reviews on telemedicine applications
      in palliative care. METHODS: A structured literature review was conducted to
      identify systematic reviews dealing with telemedicine in palliative care; the
      AMSTAR (Assessment of Multiple Systematic Reviews) checklist was used to appraise
      the evidence related to the systematic reviews. RESULTS: 405 records were
      initially identified; of these 14 were eligible for full-text analysis. In
      summary, the research strategy allowed the identification of 6 reviews to be
      included which showed a medium quality (AMSTAR score in between 4 and 7). All the
      included systematic reviews considered telemedicine applications as a feasible
      means to be used in palliative care; however, the positive findings are
      counterbalanced by several critical issues mainly related to the evidence from
      the primary studies included in each single review. CONCLUSIONS: Results of this
      first attempt to appraise the evidence in the field of telemedicine applications
      in palliative care highlighted that there is still limited evidence related to
      this approach. Strengths and weaknesses that impact on the general quality of the
      reviews were identified and relevant points to be taken into account for future
      research were suggested.

PMID- 27698304
TI  - Job stress models for predicting burnout syndrome: a review.
AB  - In Europe, the Council Directive 89/391 for improvement of workers' safety and
      health has emphasized the importance of addressing all occupational risk factors,
      and hence also psychosocial and organizational risk factors. Nevertheless, the
      construct of "work-related stress" elaborated from EU-OSHA is not totally
      corresponding with the "psychosocial" risk, that is a broader category of risk,
      comprising various and different psychosocial risk factors. The term "burnout",
      without any binding definition, tries to integrate symptoms as well as cause of
      the burnout process. In Europe, the most important methods developed for the work
      related stress risk assessment are based on the Cox's transactional model of job
      stress. Nevertheless, there are more specific models for predicting burnout
      syndrome. This literature review provides an overview of job burnout,
      highlighting the most important models of job burnout, such as the Job Strain,
      the Effort/Reward Imbalance and the Job Demands-Resources models. The difference
      between these models and the Cox's model of job stress is explored.

PMID- 27698305
TI  - Prevalence of breastfeeding in Italy: a population based follow-up study.
AB  - INTRODUCTION: Breastfeeding is widely recommended. Updated data are needed to
      assess its prevalence and the effectiveness of interventions. Breastfeeding
      practices in Italy need to be promoted and monitored with updated and standard
      data The objective of this study is to provide estimates of the prevalence of
      breastfeeding and exclusively breastfeeding and to identify factors that may be
      modified to improve them. MATERIALS AND METHODS: Two population-based follow-up
      surveys were conducted to evaluate the quality of maternal care in 25 Local
      Health Units (LHUs) in Italy during 2008-2011. Women were interviewed soon after
      giving birth and after 3, 6 and 12 months. Breastfeeding prevalences were
      estimated. A logistic regression model was used to investigate factors associated
      with exclusive breastfeeding at 3 months. RESULTS: Breastfeeding and exclusively
      breastfeeding prevalence estimates were 91.6% and 57.2% at discharge, 71.6% and
      48.6% at 3 months, 57.7% and 5.5% at 6 months. At 12 months, 32.5% were still
      breastfeeding. Women who are more likely to exclusively breastfeed at 3 months
      are multiparous, more educated, resident in the north/center, have attended
      antenatal classes and groups of breastfeeding support, have practiced the skin-to
      skin contact in hospital and have initiated breastfeeding early. CONCLUSION: In
      Italy many mothers do not comply with breastfeeding recommendations. The
      promotion and support of breastfeeding is still necessary in Italy and still
      needs to be monitored with representative data. Actions should aim at empowering
      women, reducing social inequalities and improving practices in hospitals and
      maternal care services which encourage breastfeeding.

PMID- 27698306
TI  - Absolute structure determination: pushing the limits.

PMID- 27698307
TI  - Why direct and post-refinement determinations of absolute structure may give
      different results.
AB  - Direct determination of the Flack parameter as part of the structure refinement
      procedure usually gives different, though similar, values to post-refinement
      methods. The source of this discrepancy has been probed by analysing a range of
      data sets taken from the recent literature. Most significantly, it was observed
      that the directly refined Flack (x) parameter and its standard uncertainty are
      usually not much influenced by changes in the refinement weighting schemes, but
      if they are then there are probably problems with the data or model. Post
      refinement analyses give Flack parameters strongly influenced by the choice of
      weights. Weights derived from those used in the main least squares lead to post
      refinement estimates of the Flack parameters and their standard uncertainties
      very similar to those obtained by direct refinement. Weights derived from the
      variances of the observed structure amplitudes are more appropriate and often
      yield post-refinement Flack parameters similar to those from direct refinement,
      but always with lower standard uncertainties. Substantial disagreement between
      direct and post-refinement determinations are strongly indicative of problems
      with the data, which may be difficult to identify. Examples drawn from 28
      structure determinations are provided showing a range of different underlying
      problems. It seems likely that post-refinement methods taking into account the
      slope of the normal probability plot are currently the most robust estimators of
      absolute structure and should be reported along with the directly refined values.

PMID- 27698308
TI  - Two rhodamine 6G derivative compounds: a structural and fluorescence single
      crystal study.
AB  - The synthesis, characterization, structural analysis and fluorescence properties
      of two rhodamine 6G derivatives are described, namely a propargylamine
      derivative, 3',6'-bis(ethylamino)-2',7'-dimethyl-2-(methylcyanide)spiro[isoindole
      1,9'-xanthen]-3(2H)-one (I), and a gamma-aminobutyric acid (GABA) derivative,
      3',6'-bis(ethylamino)-2',7'-dimethyl-3-oxospiro[isoindole-1,9'-xanthen]-2(3H)
      yl)butyricacid (II). Both structures are compared with four similar ones from the
      Cambridge Structural Database (CSD), and the interactions involved in the
      stabilization are analyzed using the atoms in molecules (AIM) theory. Finally, a
      single-crystal in-situ reaction study is presented, carried out by fluorescence
      methods, which enabled the 'opening' of the spirolactam ring in the solid phase.

PMID- 27698309
TI  - Br...Br and van der Waals interactions along a homologous series: crystal packing
      of 1,2-dibromo-4,5-dialkoxybenzenes.
AB  - The crystalline structures of four homologues of the 1,2-dibromo-4,5
      dialkoxybenzene series [Br2C6H2(OCnH2n + 1)2 for n = 2, 12, 14 and 18] have been
      solved by means of single-crystal crystallography. Comparison along the series,
      including the previously reported n = 10 and n = 16 derivatives, shows a clear
      metric trend (b and c essentially fixed along the series and a growing linearly
      with n), in spite of some subtle differences in space groups and/or packing
      modes. A uniform packing pattern for the aliphatic chains has been found for the
      n = 12 to 18 homologues, which slightly differs from that of the n = 10
      derivative. The crystalline structures of all the higher homologues (n = 10-18)
      seem to arise from van der Waals interchain interactions and, to a lesser extent,
      type II Br...Br interactions. The dominant role of interchain interactions
      provides direct structural support for the usual interpretation of melting point
      trends like that found along this series. Atoms in Molecules (AIM) analysis
      allows a comparison of the relative magnitude of the interchain and Br...Br
      interactions, an analysis validated by the measured melting enthalpies.

PMID- 27698310
TI  - Effect of Al and Ca co-doping, in the presence of Te, in superconducting YBCO
      whiskers growth.
AB  - High-Tc superconducting cuprates (HTSC) such as YBa2Cu3O7 - x (YBCO) are
      promising candidates for solid-state THz applications based on stacks of
      intrinsic Josephson junctions (IJJs) with atomic thickness. In view of future
      exploitation of IJJs, high-quality superconducting YBCO tape-like single crystals
      (whiskers) have been synthesized from Ca-Al-doped precursors in the presence of
      Te. The main aim of this paper is to determine the importance of the simultaneous
      use of Al, Te and Ca in promoting YBCO whiskers growth with good superconducting
      properties (Tc = 79-84 K). Further, single-crystal X-ray diffraction (SC-XRD)
      refinements of tetragonal YBCO whiskers (P4/mmm) are reported to fill the
      literature lack of YBCO structure investigations. All the as-grown whiskers have
      also been investigated by means of X-ray powder diffraction (XRPD), scanning
      electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Our
      results demonstrate that the interplay of Ca, Te and Al elements is clearly
      necessary in order to obtain superconducting YBCO whiskers. The data obtained
      from SC-XRD analyses confirm the highly crystalline nature of the whiskers grown.
      Ca and Al enter the structure by replacing the Y and the octahedral coordinated
      Cu1 site, respectively, as in other similar orthorhombic compounds, while Te does
      not enter the structure of whiskers but its presence in the precursor is
      essential to the growth of the crystals.

PMID- 27698311
TI  - Bis-(1-(2-aminoethyl)piperidino), (2-(2-aminoethyl)pyridino) and (1-(2
      aminoethyl)pyrrolidino)-substituted dicyanoquinodimethanes: consequences of
      flexible ethylene spacers with heterocyclic moieties and amine functionalities.
AB  - Heterocyclic building blocks possessing ethylene spacer and amine functionality
      such as 1-(2-aminoethyl)piperidine (1,2-AEPi), 2-(2-aminoethyl)pyridine (2,2
      AEPy) and 1-(2-aminoethyl)pyrrolidine (1,2-AEPr) were reacted with
      tetracyanoquinodimethane (TCNQ) to give disubstituted compounds namely bis-(1-(2
      aminoethyl)piperidino)dicyanoquinodimethane (1), bis-(2-(2
      aminoethyl)pyridino)dicyanoquinodimethane (2) and bis-(1-(2
      aminoethyl)pyrrolidino)dicyanoquinodimethane (3). Utilization of 1,2-AEPi, 2,2
      AEPy and 1,2-AEPr as disubstituents on TCNQ has resulted in interesting crystal
      structures. Inter- and intramolecular hydrogen-bond mediated and expanded
      supramolecular structures were observed in the lattices of the crystals. Strong
      fluorescence was observed in solids and solutions. (2) showed a strong second
      harmonic generation (SHG) whereas (1) and (3) were found to be SHG inactive. All
      compounds possess good thermal stabilities.

PMID- 27698312
TI  - CH3NH3PbI3: precise structural consequences of water absorption at ambient
      conditions.
AB  - The crystal structure of the pristine (I) and aged (II) crystals of CH3NH3PbI3
      (hereafter MAPbI3) hybrid organic-inorganic lead iodide has been studied at 293 K
      with high-precision single-crystal X-ray diffraction using a synchrotron light
      source. We show that (I) and (II) are characterized by an identical tetragonal
      unit cell but different space groups: I422 for (I) and P42212 for (II). Both
      space groups are subgroups of I4/mcm, which is widely used for MAPbI3. The main
      difference between (I) and (II) comes from the difference in hydrogen bonds
      between the MA+ cation and the PbI3 framework which is the direct consequence of
      H2O insertion in the aged crystal (II).

PMID- 27698314
TI  - Mutual transformation between crystalline phases in silicon after treatment in a
      planetary mill: HRTEM studies.
AB  - High-resolution transmission electron microscopy (HRTEM) studies of silicon after
      treatment in a planetary mill have been performed. It is shown that along with
      the initial phase of silicon, Si-I, the sample also contains some high-pressure
      phases: Si-III (Kasper phase) and Si-IV (lonsdaleite). We studied the orientation
      relationship between the particles of different phases, finding that there are,
      in general, two mechanisms of formation of Si-IV: (1) through the stacking faults
      formation; (2) through the transformation first to the Kasper phase (Si-III), and
      then from the Kasper phase to Si-IV. Estimations of temperature and pressure
      conditions in the planetary ball mill made previously are in accordance with the
      conditions of formation of the above-mentioned phases.

PMID- 27698313
TI  - Structures and physicochemical properties of vortioxetine salts.
AB  - In the present work, novel salts of the multimodal antidepressant drug
      vortioxetine (VT) were crystallized with pharmaceutically acceptable acids,
      aiming to improve the solubility of VT. The acids for VT were selected based on
      DeltapKa being greater than 2 or 3. Salts of hydrobromic acid (HBr), hydrochloric
      acid (HCl), p-hydroxybenzoic acid (PHBA), saccharin (SAC) and L-aspartic acid
      (ASP) were reported. All salts were characterized by single-crystal X-ray
      diffraction, FT-IR, powder X-ray diffraction (PXRD) and differential scanning
      calorimetry (DSC). The acidic proton is transferred to the secondary N atom on
      the piperazine ring of VT, forming the charge-assisted hydrogen bond N+-H...X- (X
      = Cl, Br, O). Solubility and intrinsic dissolution rate (IDR) experiments were
      carried out in distilled water (pH = 7.0) to compare the solubilities of the
      salts with that of VT. The VT-ASP-H2O (1:1:2) salt showed 414 times higher
      solubility and 1722 times faster IDR compared with VT. VT-ASP-H2O (1:1:2) is a
      high solubility salt that is stable in a slurry experiment at 298 K in 95%
      ethanol. The experimental data for the VT-ASP-H2O (1:1:2) salt identify it as a
      promising drug candidate.

PMID- 27698315
TI  - Accurate unrestrained DDM refinement of crystal structures from highly distorted
      and low-resolution powder diffraction data.
AB  - The structure of benzene:ethane co-crystal at 90 K is refined with anisotropic
      displacement parameters without geometric restraints from high-resolution
      synchrotron X-ray powder diffraction (XRPD) data using the derivative difference
      method (DDM) with properly chosen weighting schemes. The average C-C bond
      precision achieved is 0.005 A and the H-atom positions in ethane are refined
      independently. A new DDM weighting scheme is introduced that compensates for big
      distortions of experimental data. The results are compared with density
      functional theory (DFT) calculations reported by Maynard-Casely et al. [(2016).
      IUCrJ, 3, 192-199] where a rigid-body Rietveld refinement was also applied to the
      same dataset due to severe distortions of the powder pattern attributable to
      experimental peculiarities. For the crystal structure of 2-aminopyridinium
      fumarate-fumaric acid formerly refined applying 77 geometric restraints by Dong
      et al. [(2013). Acta Cryst. C69, 896-900], an unrestrained DDM refinement using
      the same XRPD pattern surprisingly gave two times narrower dispersion of
      interatomic distances.

PMID- 27698317
TI  - Crystal chemistry of trialkylsilyl-capped (3Z)-4-(methylthio)-3-penten-1-yne:
      polymorphism, twinning and ambiguity of order-disorder descriptions.
AB  - The crystallization behavior of trimethylsilyl-capped (3Z)-4-(methylthio)-3
      penten-1-yne (1-TMS) and the triisopropylsilyl and tert-butyldimethylsilyl
      analogues (1-TIPS) and (1-TBDMS) was investigated. (1-TMS) crystallizes in the
      Sohncke space group P212121 with Z' = 1. (1-TIPS) exists as two polymorphs, both
      crystallizing in P?overline 1 with Z' = 2 independent molecules. Polymorph (I) is
      an order-disorder (OD) twin. Two interpretations in terms of M = 1 or M = 2 kinds
      of OD layers are possible, with different degrees of idealization. Polymorph (II)
      is fully ordered (non-twinned). Its structure can be derived from polymorph (I)
      by inverting the orientation of every second molecule. (1-TBDMS) (P?overline1, Z'
      = 2) is an OD twin, where the OD description is unambiguously in M = 1 kinds of
      layers.

PMID- 27698316
TI  - Towards a revisitation of vesuvianite-group nomenclature: the crystal structure
      of Ti-rich vesuvianite from Alchuri, Shigar Valley, Pakistan.
AB  - Vesuvianite containing 5.85 wt% TiO2 from an Alpine-cleft-type assemblage
      outcropped near Alchuri, Shigar Valley, Northern Areas, Pakistan, has been
      investigated by means of electron microprobe analyses, gas-chromatographic
      analysis of H2O, X-ray powder diffraction, single-crystal X-ray structure
      refinement, 27Al NMR, 57Fe Mossbauer spectroscopy, IR spectroscopy and optical
      measurements. Tetragonal unit-cell parameters are: a = 15.5326 (2), c = 11.8040
      (2) A, space group P4/nnc. The structure was refined to final R1 = 0.031, wR2 =
      0.057 for 11247 I > 2sigma(I). A general crystal-chemical formula of studied
      sample can be written as follows (Z = 2): [8-9](Ca17.1Na0.9)
      [8]Ca1.0[5](Fe2+0.44Fe3+0.34Mg0.22) [6](Al3.59Mg0.41)
      [6](Al4.03Ti2.20Fe3+1.37Fe2+0.40) (Si18O68) [(OH)5.84O2.83F1.33]. The octahedral
      site Y2 is Al-dominant and does not contain transition elements. Another
      octahedral site Y3 is also Al-dominant and contains Fe2+, Fe3+ and Ti. The site
      Y1 is split into Y1a and Y1b predominantly occupied by Fe2+ and Fe3+,
      respectively. The role of the Y1 site in the diversity of vesuvianite-group
      minerals is discussed.

PMID- 27698318
TI  - Variable-temperature X-ray diffraction study of structural parameters of NH---S
      hydrogen bonds in triethylammonium and pyridinium silanethiolates.
AB  - Two hydrogen-bonded, well defined compounds were synthesized from tris(2,6
      diisopropyl)phenoxysilanethiol (TDST) and triethylamine (TDST-TEA) or pyridine
      (TDST-py). The crystalline compounds were characterized in the solid state by
      variable-temperature X-ray diffraction measurements and ATR FT-IR spectroscopy.
      The toluene solutions of TDST-TEA and TDST-py were studied by NMR spectroscopy.
      The total hydrogen-bond energies and FT-IR spectra were calculated with the use
      of BLYP-D/TZP and B3LYP/6-31G(d,p)/GD3BJ methods. Thermochemical parameters and
      potential energy scans were calculated at the B3LYP/6-31G(d,p)/GD3BJ level. All
      results point to the higher energy of bonding in TDST-TEA both in the solid state
      and in solution. At the same time the potential energy scan reveals a very broad
      double-well hydrogen bond in TDST-py, indicating good stabilization of the system
      for a wide range of D-H...A distances.

PMID- 27698319
TI  - The orthorhombic pseudopolymorph of tacrine hydrochloride.
AB  - Crystallization of tacrine hydrochloride, an acetylcholinesterase inhibitor used
      during treatment of mild to moderate Alzheimer's disease, from a water:ethanol
      solution has resulted in an orthorhombic pseudopolymorph. This orthorhombic form
      which occurs as a dihydrate shows columns of stacking acridines together with
      continuous Cl-Owater-Owater-Cl chains and ladder-like ribbons composed of squares
      and hexagons.

PMID- 27698320
TI  - Topological characterization of electron density, electrostatic potential and
      intermolecular interactions of 2-nitroimidazole: an experimental and theoretical
      study.
AB  - An experimental charge density distribution of 2-nitroimidazole was determined
      from high-resolution X-ray diffraction and the Hansen-Coppens multipole model.
      The 2-nitroimidazole compound was crystallized and a high-angle X-ray diffraction
      intensity data set has been collected at low temperature (110 K). The structure
      was solved and further, an aspherical multipole model refinement was performed up
      to octapole level; the results were used to determine the structure, bond
      topological and electrostatic properties of the molecule. In the crystal, the
      molecule exhibits a planar structure and forms weak and strong intermolecular
      hydrogen-bonding interactions with the neighbouring molecules. The Hirshfeld
      surface of the molecule was plotted, which explores different types of
      intermolecular interactions and their strength. The topological analysis of
      electron density at the bond critical points (b.c.p.) of the molecule was
      performed, from that the electron density rhobcp(r) and the Laplacian of electron
      density ?2rhobcp(r) at the b.c.p.s of the molecule have been determined; these
      parameters show the charge concentration/depletion of the nitroimidazole bonds in
      the crystal. The electrostatic parameters like atomic charges and the dipole
      moment of the molecule were calculated. The electrostatic potential surface of
      the molecule has been plotted, and it displays a large electronegative region
      around the nitro group. All the experimental results were compared with the
      corresponding theoretical calculations performed using CRYSTAL09.

PMID- 27698321
TI  - Communication between cation environments in aluminosilicate frameworks:
      incommensurately modulated crystal structure of an e-plagioclase.
AB  - Despite being one of the most common minerals in the earth's crust the crystal
      structure of intermediate e-plagioclase remains only partially understood, due in
      a large part to its complex diffraction patterns including satellite reflections.
      In this article we present a detailed analysis of the structure of e-plagioclase
      (An44) using single-crystal X-ray diffraction measured at ambient and low
      temperature (T = 100 K), in which the full modulated structure is successfully
      refined. As in earlier studies, the diffraction pattern exhibits strong main a
      reflections and weak e-satellite reflections. The average structure could be
      solved in terms of an albite-like basic cell with the triclinic centrosymmetric
      and non-centrosymmetric space groups P ?bar 1 and P1 (treated in its C ?bar 1 and
      C1 setting, respectively, to follow conventions in the literature), while the
      incommensurately modulated structure was modeled in (3 + 1)D superspace,
      employing both the centro- and non-centrosymmetric superspace groups X ?bar
      1(alphabetagamma)0 and X1(alphabetagamma)0, where X refers to a special (3 + 1)D
      lattice centering with centering vectors (0 0 1/2 1/2), (1/2 1/2 0 1/2), and (1/2
      1/2 1/2 0). Individual positional and occupational modulations for Ca/Na were
      refined with deeper insights being revealed in the non-centrosymmetric structure
      model. Through the structural details emerging from this model, the origin of the
      modulation can be traced to the communication between Ca/Na site positions
      through their bridging aluminosilicate (Si/Al)O4 tetrahedra.

PMID- 27698323
TI  - Functional Magnetic Resonance Imaging Correlates of First-Episode Psychoses
      during Attentional and Memory Task Performance.
AB  - BACKGROUND: The nature of the alteration of the response to cognitive tasks in
      first-episode psychosis (FEP) still awaits clarification. We used activation
      likelihood estimation, an increasingly used method in evaluating normal and
      pathological brain function, to identify activation changes in functional
      magnetic resonance imaging (fMRI) studies of FEP during attentional and memory
      tasks. METHODS: We included 11 peer-reviewed fMRI studies assessing FEP patients
      versus healthy controls (HCs) during performance of attentional and memory tasks.
      RESULTS: Our database comprised 290 patients with FEP, matched with 316 HCs.
      Between-group analyses showed that HCs, compared to FEP patients, exhibited
      hyperactivation of the right middle frontal gyrus (Brodmann area, BA, 9), right
      inferior parietal lobule (BA 40), and right insula (BA 13) during attentional
      task performances and hyperactivation of the left insula (BA 13) during memory
      task performances. CONCLUSIONS: Right frontal, parietal, and insular dysfunction
      during attentional task performance and left insular dysfunction during memory
      task performance are significant neural functional FEP correlates.

PMID- 27698324
TI  - Cytomorphologic and Immunophenotypic Profile of a Cohort of Small Cell Carcinoma
      of the Urinary Bladder.
AB  - BACKGROUND: The incidence of primary small cell carcinoma (SCC) of the urinary
      bladder is extremely rare. We sought to analyze the cytologic and
      immunophenotypic features of SCC of the urinary bladder in urine and reassert the
      importance of cytologic examination of urine specimens for diagnosis of this
      tumor. METHODS: We studied the clinical and cytomorphologic features in the
      presurgical urine specimens (4 voided urine and 2 bladder-washing specimens) of
      histopathologically and immunohistochemically proven cases of SCC of the urinary
      bladder. RESULTS: There were 6 cases, all males, with an age range of 61-81
      years. On cytologic and histopathologic examination, typical SCC morphology was
      present in all cases. On immunohistochemistry, synaptophysin and CD56 were
      positive in all 6 cases, while chromogranin was positive in only 3. The Ki-67
      labeling index ranged from 30 to 100%. CONCLUSIONS: SCC should be kept in the
      differential diagnosis, when high-grade urothelial carcinoma is suspected in a
      urine cytology specimen, as this distinction has important therapeutic and
      prognostic implications. Therefore, a careful observation and, if required, the
      use of an appropriate immunocytochemical panel on the presurgical urine specimens
      can lead to a correct diagnosis.

PMID- 27698325
TI  - Use of an Image Acquisition Stabilizer Improves Sidestream Dark Field Imaging of
      the Serosa during Open Gastrointestinal Surgery.
AB  - AIM: To investigate whether an image acquisition stabilizer (IAS) mounted on the
      sidestream dark field camera (SDF) during gastrointestinal surgery improves image
      stability and acquisition. METHODS: Serosal SDF imaging was compared with SDF
      imaging combined with an IAS (SDF + IAS) during gastrointestinal surgery.
      Stability was assessed as the image drift in pixels and the time to obtain stable
      images. The success rate was determined as the percentage of analyzable images
      after recording. The effect of negative pressure from the IAS was determined
      during single-spot measurements and by comparing microvascular parameters between
      groups. Data are presented as mean +/- SD. RESULTS: Sixty serosal measurements
      were performed per group; 87% were successful in the SDF group and 100% in the
      SDF + IAS group (p = 0.003). Image drift in the SDF group was 148 +/- 36 versus
      55 +/- 15 pixels in the SDF + IAS group; p < 0.001. Time to stable image was 96
      +/- 60 s in the SDF group versus 57 +/- 31 s in the SDF + IAS group; p = 0.03. No
      effect of negative pressure was seen. CONCLUSION: The use of an IAS mounted on an
      SDF camera during serosal microvascular assessment improves the success rate of
      image acquisition and stability and reduces the time to stable image with no
      effect on the microcirculation.

PMID- 27698327
TI  - Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case
      Study.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease.
      Most patients require long-term therapy with systemic steroids, and a steroid
      sparing agent is usually also utilized. Dapsone is a chemotherapeutic agent with
      anti-inflammatory properties that is used as a steroid-sparing agent in PV.
      OBJECTIVE: The aim of the present study was to evaluate the efficacy of dapsone
      as an adjuvant therapy in patients with PV. METHODS: A retrospective analysis of
      patients' files was performed. All 26 patients included in the study group were
      treated with dapsone as an adjuvant to systemic steroids for at least 3
      consecutive months and were followed up during their dapsone treatment period.
      RESULTS: After 3 months of treatment with dapsone, 13 patients were in the
      consolidation phase, 4 patients demonstrated partial remission on minimal
      therapy, 7 patients demonstrated complete remission on minimal therapy, and 2
      patients were defined as treatment failures. The trend of clinical improvement
      continued after 6 months of treatment and at the study end point. CONCLUSION:
      This retrospective case series, one of the largest reported, indicates that
      dapsone is efficacious and safe for patients with PV in whom it is well tolerated
      soon after the initiation of treatment.

PMID- 27698326
TI  - On-Pump versus Off-Pump Complete Arterial Revascularization Using Bilateral
      Internal Mammary Arteries and the T-Graft Technique: Clinical and Angiographic
      Results for 3,445 Patients in 13 Years of Follow-Up.
AB  - BACKGROUND: This is an investigation of complete arterial coronary artery bypass
      grafting (CACABG) using bilateral internal mammary arteries (IMA) and the T-graft
      technique either on- or off-pump as a routine approach to treat coronary artery
      disease. METHODS: Between January 2000 and December 2012, 3,445 patients
      underwent on-pump (n = 2,216) or off-pump (n = 1,229) CACABG. A 30-day follow-up
      was performed prospectively, a long-term follow-up by a questionnaire, and
      coronary angiography in selected patients. RESULTS: End points at 30 days were
      death, myocardial infarction, stroke, repeat revascularization, renal
      replacement, reoperation, sternal wound infection and atrial fibrillation.
      FitzGibbon A patency rates were 89.8 vs. 91.4% (p = 0.464) with consecutive
      percutaneous coronary intervention in the grafted area of 1.8 vs. 1.1% (p =
      0.693) on- vs. off-pump, and no reoperation in the grafted area in both groups.
      CONCLUSION: CACABG by use of skeletonized bilateral IMA with the T-graft
      technique performed either on- or off-pump is a safe and effective approach.

PMID- 27698328
TI  - In memoriam: Professor Karel Horky.

PMID- 27698329
TI  - The conundrum of watchful waiting versus pre-emptive surgery in asymptomatic
      aortic stenosis: are we any closer to an answer?

PMID- 27698330
TI  - Asymmetric dimethylarginine: a risk indicator or pathogenic factor?

PMID- 27698331
TI  - Small intestinal bacterial overgrowth in adult patients with type 1 diabetes.

PMID- 27698333
TI  - Recurrent asymptomatic acute cellular rejection after heart transplantation:
      monitoring with speckle-tracking echocardiography.

PMID- 27698332
TI  - The moving target of clopidogrel response variability: new tricks of the old dog?

PMID- 27698334
TI  - Novel truncating desmoplakin mutation as a potential cause of sudden cardiac
      death in a family.

PMID- 27698336
TI  - Whether and how can the doctor help the patient who asks for death?

PMID- 27698335
TI  - Ibrutinib-induced pyoderma gangrenosum.

PMID- 27698337
TI  - The Potential Role of IL-33 in Renal Transplant Recipients with Chronic Allograft
      Dysfunction.
AB  - BACKGROUND Chronic allograft dysfunction (CAD) is the major factor endangering
      the long-term allograft survival in kidney transplantation. The mechanisms of CAD
      remain unclear. MATERIAL AND METHODS A total of 64 renal transplant recipients
      were enrolled in our study and divided into a stable group and CAD group
      according to their allograft function. A group of 32 normal controls (healthy
      volunteers) were also included. An ELISA was used to detect serum interleukin-33
      (IL-33), IL-2, IL-4, IL-10, IL-17, and interferon-gamma (IFN-gamma). Flow
      cytometry was performed to measure the percentage of CD3+CD4+ and CD3+CD8+ T
      cells in the peripheral blood from the three patient groups. The correlations
      among the study indexes were also analyzed using Pearson's method. RESULTS Levels
      of serum IL-33 was significantly higher in CAD patients than recipients with
      stable allograft function. Moreover, serum IL-2, IL-4, and IL-10 also increased
      statistically in patients with CAD. In addition, significant differences were
      observed in CD4+ T cells and the ratio of CD4+ and CD8+ T cells between CAD and
      stable patients. CONCLUSIONS Serum upregulated IL-33 could contribute to the
      pathogenesis of CAD in kidney transplant recipients.

PMID- 27698338
TI  - Alacrima as a Harbinger of Adrenal Insufficiency in a Child with Allgrove (AAA)
      Syndrome.
AB  - BACKGROUND Allgrove syndrome, or triple "A" syndrome (3A syndrome), is a rare
      autosomal recessive syndrome with variable phenotype, and an estimated prevalence
      of 1 per 1,000,000 individuals. Patients usually display the triad of achalasia,
      alacrima, and adrenocorticotropin (ACTH) insensitive adrenal insufficiency,
      though the presentation is inconsistent. CASE REPORT Here, the authors report a
      case of Allgrove syndrome in a pediatric patient with delayed diagnosis in order
      to raise awareness of this potentially fatal disease as a differential diagnosis
      of alacrima. CONCLUSIONS The prevalence of Allgrove syndrome may be much higher
      as a result of underdiagnosis and missed diagnosis due to the variable
      presentation and sudden unexplained childhood death from adrenal crisis. The
      authors review the characteristic symptoms of Allgrove syndrome in relation to
      the case study in order to avoid missed or delayed diagnosis, potentially
      decreasing morbidity, and mortality in those affected by this disease.

PMID- 27698339
TI  - Total Arterial Revascularization: Bypassing Antiquated Notions to Better
      Alternatives for Coronary Artery Disease.
AB  - Total arterial revascularization is the leading trend in coronary artery bypass
      grafting (CABG) for the treatment of coronary artery disease (CAD). Adding to its
      superiority to vein conduits, arteries allow for a high degree of versatility and
      long-term patency, while minimizing the need for reintervention. This is
      especially important for patients with multi-vessel coronary artery disease, as
      well as young patients. However, arterial revascularization has come a long way
      before being widely appreciated, with some yet unresolved debates, and advances
      that never cease to impress. In this review, we discuss the evolution of this
      surgical technique and its clinical success, as well as its most conspicuous
      limitations in light of accumulated published date from decades of experience.

PMID- 27698340
TI  - Golgi Phosphoprotein 3 Inhibits the Apoptosis of Human Glioma Cells in Part by
      Downregulating N-myc Downstream Regulated Gene 1.
AB  - BACKGROUND Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in
      the development of several human cancers. Our previous study showed that GOLPH3
      expression in glioma tissues was related to the severity of the malignancy of the
      cancer. However, the mechanism by which GOLPH3 affects cell apoptosis is largely
      unknown. The present study was designed to explore the possible mechanism of
      GOLPH3 in cell apoptosis. MATERIAL AND METHODS To analyze the biological role of
      GOLPH3 in glioma cells, we used GOLPH3 small interference RNA in apoptosis of
      glioma cells. The apoptosis of glioma cells was detected by flow cytometry. The
      expression level of GOLPH3 and NDRG1 protein was determined by Western blot
      analyses and immunohistochemical staining, respectively, to evaluate their
      association with glioma. Tumor tissues were collected from patients with glioma.
      Normal cerebral tissues were acquired from cerebral trauma patients undergoing
      internal decompression surgery. RESULTS We confirm that the decrease of GOLPH3
      that promotes the apoptosis of glioma cells may be regulated by the activation of
      NDRG1 and cleaved capcase 3. There was a inverse association between GOLPH3 and
      NDRG1 in glioma samples. CONCLUSIONS Our findings indicate that GOLPH3 and NDRG1
      both play an important role in glioma etiology. Either GOLPH3 or NDRG1 might be a
      potential candidate for malignant glioma therapy.

PMID- 27698341
TI  - Self-amplified photo-induced gap quenching in a correlated electron material.
AB  - Capturing the dynamic electronic band structure of a correlated material presents
      a powerful capability for uncovering the complex couplings between the electronic
      and structural degrees of freedom. When combined with ultrafast laser excitation,
      new phases of matter can result, since far-from-equilibrium excited states are
      instantaneously populated. Here, we elucidate a general relation between
      ultrafast non-equilibrium electron dynamics and the size of the characteristic
      energy gap in a correlated electron material. We show that carrier multiplication
      via impact ionization can be one of the most important processes in a gapped
      material, and that the speed of carrier multiplication critically depends on the
      size of the energy gap. In the case of the charge-density wave material 1T-TiSe2,
      our data indicate that carrier multiplication and gap dynamics mutually amplify
      each other, which explains-on a microscopic level-the extremely fast response of
      this material to ultrafast optical excitation.

PMID- 27698342
TI  - Comparative survey of the relative impact of mRNA features on local ribosome
      profiling read density.
AB  - Ribosome profiling (Ribo-seq), a promising technology for exploring ribosome
      decoding rates, is characterized by the presence of infrequent high peaks in
      ribosome footprint density and by long alignment gaps. Here, to reduce the impact
      of data heterogeneity we introduce a simple normalization method, Ribo-seq Unit
      Step Transformation (RUST). RUST is robust and outperforms other normalization
      techniques in the presence of heterogeneous noise. We illustrate how RUST can be
      used for identifying mRNA sequence features that affect ribosome footprint
      densities globally. We show that a few parameters extracted with RUST are
      sufficient for predicting experimental densities with high accuracy. Importantly
      the application of RUST to 30 publicly available Ribo-seq data sets revealed a
      substantial variation in sequence determinants of ribosome footprint frequencies,
      questioning the reliability of Ribo-seq as an accurate representation of local
      ribosome densities without prior quality control. This emphasizes our incomplete
      understanding of how protocol parameters affect ribosome footprint densities.

PMID- 27698343
TI  - Green tea reduces body fat via upregulation of neprilysin.
AB  - BACKGROUND/OBJECTIVE: Consumption of green tea has become increasingly popular,
      particularly because of claimed reduction in body weight. We recently reported
      that animals with pharmacological inhibition (by candoxatril) or genetic absence
      of the endopeptidase neprilysin (NEP) develop an obese phenotype. We now
      investigated the effect of green tea extract (in drinking water) on body weight
      and body composition and the mediating role of NEP. SUBJECTS/METHODS: To
      elucidate the role of NEP in mediating the beneficial effects of green tea
      extract, 'Berlin fat mice' or NEP-deficient mice and their age- and gender
      matched wild-type controls received the extract in two different doses (300 or
      600 mg kg-1 body weight per day) in the drinking water. RESULTS: In 'Berlin fat
      mice', 51 days of green tea treatment did not only prevent fat accumulation
      (control: day 0: 30.5% fat, day 51: 33.1%; NS) but also reduced significant body
      fat (green tea: day 0: 27.8%, day 51: 20.9%, P<0.01) and body weight below the
      initial levels. Green tea reduced food intake. This was paralleled by a selective
      increase in peripheral (in kidney 17%, in intestine 92%), but not central NEP
      expression and activity, leading to downregulation of orexigens (like galanin and
      neuropeptide Y (NPY)) known to be physiological substrates of NEP. Consequently,
      in NEP-knockout mice, green tea extract failed to reduce body fat/weight.
      CONCLUSIONS: Our data generate experimental proof for the assumed effects of
      green tea on body weight and the key role for NEP in such process, and thus open
      a new avenue for the treatment of obesity.

PMID- 27698345
TI  - Weight losses with low-energy formula diets in obese patients with and without
      type 2 diabetes: systematic review and meta-analysis.
AB  - AIM: To provide a systematic review, of published data, to compare weight losses
      following very low calorie (<800 kcal per day VLCD) or low-energy liquid-formula
      (>800 kcal per day LELD) diets, in people with and without type 2 diabetes
      mellitus (T2DM). METHODS: Systematic electronic searches of Medline (1946-2015)
      and Embase (1947-2015) to identify published studies using formula total diet
      replacement diets (VLCD/LELD). Random effects meta-analysis using weighted mean
      difference (WMD) in body weight between groups (with and without diabetes) as the
      summary estimate. RESULTS: Final weight loss, in the five included studies,
      weighted for study sizes, (n=569, mean BMI=35.5-42.6 kg/m2), was not
      significantly different between participants with and without T2DM: -1.2 kg; 95%
      CI: -4.1 to 1.6 kg). Rates of weight loss were also similar in the two groups 
      0.6 kg per week (T2DM) and 0.5 kg per week (no diabetes), and for VLCD (<800 kcal
      per day) and LELD (>800 kcal per day). CONCLUSIONS: Weight losses with liquid
      formula diets are very similar for VLCD and LELD and for obese subjects with or
      without T2DM. They can potentially achieve new weight loss/ maintenance targets
      of >15-20% for people with severe and medically complicated obesity.

PMID- 27698344
TI  - Maternal vitamin D beneficially programs metabolic, gut and bone health of mouse
      male offspring in an obesogenic environment.
AB  - BACKGROUND/OBJECTIVES: Vitamin D is an anti-inflammatory nutrient and a
      determinant of bone health. Some prospective studies suggest that maternal
      vitamin D status is positively associated with offspring bone mass. We found that
      serum concentrations of lipopolysaccharide (LPS), an inflammatory molecule
      related to adiposity, insulin resistance and bone resorption, is lower in healthy
      mouse offspring exposed to high dietary vitamin D during pregnancy and lactation.
      LPS reaches the circulation via the gut. This study investigated whether maternal
      vitamin D programs metabolic, gut and bone health of male offspring in an
      obesogenic environment. METHODS: C57BL/6J dams received an AIN-93G diet with high
      (H) or low (L) vitamin D during pregnancy and lactation. At weaning, offspring
      remained on their dam's vitamin D level (LL or HH) or were switched (LH or HL)
      and fed a high fat (44.2%) and sucrose (19.8%) diet. Glucose response, adiposity,
      systemic inflammation (LPS, cytokines), intestinal permeability and mass,
      strength and microarchitecture of trabecular and cortical bone were assessed in 7
      month-old male offsprings. RESULTS: Higher maternal dietary vitamin D resulted in
      lower intestinal permeability (fecal albumin, P=0.010) and benefited trabecular
      but not cortical bone structure at the distal femur (higher trabecular number,
      P=0.022; less trabecular separation, P=0.015) and lumbar vertebra 2 (bone
      volume/total volume%, P=0.049). Higher maternal and offspring vitamin D resulted
      in lower fasting glucose (HH versus LL, P=0.039) and serum LPS concentrations
      (dam diet, P=0.011; pup diet, P=0.002). Higher offspring vitamin D resulted in
      lower epididymal fat pad relative weight (P=0.006). The serum concentrations of
      IL-6 and TNF-alpha did not differ among groups. CONCLUSIONS: Maternal dietary
      vitamin D beneficially programs intestinal permeability and systemic LPS
      concentration, which is accompanied by stronger trabecular bone in an obesogenic
      environment. Thus, the gut may mediate vitamin D effects. Moreover, optimizing
      vitamin D in early life may be critical for later health.

PMID- 27698347
TI  - Body composition-derived BMI cut-offs for overweight and obesity in Indians and
      Creoles of Mauritius: comparison with Caucasians.
AB  - BACKGROUND AND AIMS: Global estimates of overweight and obesity prevalence are
      based on the World Health Organisation (WHO) body mass index (BMI) cut-off values
      of 25 and 30 kg m-2, respectively. To validate these BMI cut-offs for adiposity
      in the island population of Mauritius, we assessed the relationship between BMI
      and measured body fat mass in this population according to gender and ethnicity.
      METHODS: In 175 young adult Mauritians (age 20-42 years) belonging to the two
      main ethnic groups-Indians (South Asian descent) and Creoles (African/Malagasy
      descent), body weight, height and waist circumference (WC) were measured, total
      body fat assessed by deuterium oxide (D2O) dilution and trunk (abdominal) fat by
      segmental bioimpedance analysis. RESULTS: Compared to body fat% predicted from
      BMI using Caucasian-based equations, body fat% assessed by D2O dilution in
      Mauritians was higher by 3-5 units in Indian men and women as well as in Creole
      women, but not in Creole men. This gender-specific ethnic difference in body
      composition between Indians and Creoles is reflected in their BMI-Fat%
      relationships, as well as in their WC-Trunk Fat% relationships. Overall, WHO BMI
      cut-offs of 25 and 30 kg m-2 for overweight and obesity, respectively, seem valid
      only for Creole men (~24 and 29.5, respectively), but not for Creole women whose
      BMI cut-offs are 2-4 units lower (21-22 for overweight; 27-28 for obese) nor for
      Indian men and women whose BMI cut-offs are 3-4 units lower (21-22 for
      overweight; 26-27 for obese). CONCLUSIONS: The use of BMI cut-off points for
      classifying overweight and obesity need to take into account both ethnicity and
      gender to avoid gross adiposity status misclassification in this population known
      to be at high risk for type-2 diabetes and cardiovascular diseases. This is
      particularly of importance in obesity prevention strategies both in clinical
      medicine and public health.

PMID- 27698346
TI  - Relevance of omental pericellular adipose tissue collagen in the pathophysiology
      of human abdominal obesity and related cardiometabolic risk.
AB  - BACKGROUND: Adipose tissue fibrosis is a relatively new notion and its
      relationship with visceral obesity and cardiometabolic alterations remains
      unclear, particularly in moderate obesity. OBJECTIVE: Our objective was to
      examine if total and pericellular collagen accumulation are relevant for the
      pathophysiology of visceral obesity and related cardiometabolic risk. SUBJECTS
      AND METHODS: Surgical omental (OM) and subcutaneous (SC) fat samples were
      obtained in 56 women (age: 47.2+/-5.8 years; body mass index (BMI): 27.1+/-4.4
      kg/m2). Body composition and fat distribution were measured by dual-energy X-ray
      absorptiometry and computed tomography, respectively. Total and pericellular
      collagen were measured using picrosirius red staining. CD68+ cells (total
      macrophages) and CD163+ cells (M2-macrophages) were identified using
      immunohistochemistry. RESULTS: We found that only pericellular collagen
      percentage, especially in OM fat, was associated with higher BMI, body fat mass
      and adipose tissue areas as well as lower radiologic attenuation of visceral
      adipose tissue and altered cardiometabolic risk variables. Strong correlations
      between peri-adipocyte collagen percentage and total or M2-macrophage percentages
      were observed in both depots. Total collagen percentage in either compartment was
      not related to adiposity, fat distribution or cardiometabolic risk. CONCLUSIONS:
      As opposed to whole tissue-based assessments of adipose tissue fibrosis, collagen
      deposition around the adipocyte, especially in the OM fat compartment is related
      to total and regional adiposity as well as altered cardiometabolic risk profile.

PMID- 27698349
TI  - Retraction: Are circRNAs involved in cancer pathogenesis?

PMID- 27698348
TI  - Multicolour synthesis in lanthanide-doped nanocrystals through cation exchange in
      water.
AB  - Meeting the high demand for lanthanide-doped luminescent nanocrystals across a
      broad range of fields hinges upon the development of a robust synthetic protocol
      that provides rapid, just-in-time nanocrystal preparation. However, to date,
      almost all lanthanide-doped luminescent nanomaterials have relied on direct
      synthesis requiring stringent controls over crystal nucleation and growth at
      elevated temperatures. Here we demonstrate the use of a cation exchange strategy
      for expeditiously accessing large classes of such nanocrystals. By combining the
      process of cation exchange with energy migration, the luminescence properties of
      the nanocrystals can be easily tuned while preserving the size, morphology and
      crystal phase of the initial nanocrystal template. This post-synthesis strategy
      enables us to achieve upconversion luminescence in Ce3+ and Mn2+-activated
      hexagonal-phased nanocrystals, opening a gateway towards applications ranging
      from chemical sensing to anti-counterfeiting.

PMID- 27698351
TI  - Contextuality without nonlocality in a superconducting quantum system.
AB  - Classical realism demands that system properties exist independently of whether
      they are measured, while noncontextuality demands that the results of
      measurements do not depend on what other measurements are performed in
      conjunction with them. The Bell-Kochen-Specker theorem states that noncontextual
      realism cannot reproduce the measurement statistics of a single three-level
      quantum system (qutrit). Noncontextual realistic models may thus be tested using
      a single qutrit without relying on the notion of quantum entanglement in contrast
      to Bell inequality tests. It is challenging to refute such models experimentally,
      since imperfections may introduce loopholes that enable a realist interpretation.
      Here we use a superconducting qutrit with deterministic, binary-outcome readouts
      to violate a noncontextuality inequality while addressing the detection,
      individual-existence and compatibility loopholes. This evidence of state
      dependent contextuality also demonstrates the fitness of superconducting quantum
      circuits for fault-tolerant quantum computation in surface-code architectures,
      currently the most promising route to scalable quantum computing.

PMID- 27698352
TI  - Nanoscale structural oscillations in perovskite oxides induced by oxygen
      evolution.
AB  - Understanding the interaction between water and oxides is critical for many
      technological applications, including energy storage, surface wetting/self
      cleaning, photocatalysis and sensors. Here, we report observations of strong
      structural oscillations of Ba0.5Sr0.5Co0.8Fe0.2O3-delta (BSCF) in the presence of
      both H2O vapour and electron irradiation using environmental transmission
      electron microscopy. These oscillations are related to the formation and collapse
      of gaseous bubbles. Electron energy-loss spectroscopy provides direct evidence of
      O2 formation in these bubbles due to the incorporation of H2O into BSCF. SrCoO3
      delta was found to exhibit small oscillations, while none were observed for
      La0.5Sr0.5CoO3-delta and LaCoO3. The structural oscillations of BSCF can be
      attributed to the fact that its oxygen 2p-band centre is close to the Fermi
      level, which leads to a low energy penalty for oxygen vacancy formation, high ion
      mobility, and high water uptake. This work provides surprising insights into the
      interaction between water and oxides under electron-beam irradiation.

PMID- 27698350
TI  - A regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma
      phenotypes through FZD6-modulated pathways.
AB  - Molecularly defined subclassification is associated with phenotypic malignancy of
      glioblastoma (GBM). However, current understanding of the molecular basis of
      subclass conversion that is often involved in GBM recurrence remain rudimentary
      at best. Here we report that canonical Wnt signalling that is active in proneural
      (PN) but inactive in mesenchymal (MES) GBM, along with miR-125b and miR-20b that
      are expressed at high levels in PN compared with MES GBM, comprise a regulatory
      circuit involving TCF4-miR-125b/miR-20b-FZD6. FZD6 acts as a negative regulator
      of this circuit by activating CaMKII-TAK1-NLK signalling, which, in turn,
      attenuates Wnt pathway activity while promoting STAT3 and NF-kappaB signalling
      that are important regulators of the MES-associated phenotype. These findings are
      confirmed by targeting differentially enriched pathways in PN versus MES GBM that
      results in inhibition of distinct GBM subtypes. Correlative expressions of the
      components of this circuit are prognostic relevant for clinical GBM. Our findings
      provide insights for understanding GBM pathogenesis and for improving treatment
      of GBM.

PMID- 27698353
TI  - Complete prevention of blood loss with self-sealing haemostatic needles.
AB  - Bleeding is largely unavoidable following syringe needle puncture of biological
      tissues and, while inconvenient, this typically causes little or no harm in
      healthy individuals. However, there are certain circumstances where syringe
      injections can have more significant side effects, such as uncontrolled bleeding
      in those with haemophilia, coagulopathy, or the transmission of infectious
      diseases through contaminated blood. Herein, we present a haemostatic hypodermic
      needle able to prevent bleeding following tissue puncture. The surface of the
      needle is coated with partially crosslinked catechol-functionalized chitosan that
      undergoes a solid-to-gel phase transition in situ to seal punctured tissues.
      Testing the capabilities of these haemostatic needles, we report complete
      prevention of blood loss following intravenous and intramuscular injections in
      animal models, and 100% survival in haemophiliac mice following syringe puncture
      of the jugular vein. Such self-sealing haemostatic needles and adhesive coatings
      may therefore help to prevent complications associated with bleeding in more
      clinical settings.

PMID- 27698355
TI  - Non-Hermitian engineering of single mode two dimensional laser arrays.
AB  - A new scheme for building two dimensional laser arrays that operate in the single
      supermode regime is proposed. This is done by introducing an optical coupling
      between the laser array and lossy pseudo-isospectral chains of photonic
      resonators. The spectrum of this discrete reservoir is tailored to suppress all
      the supermodes of the main array except the fundamental one. This spectral
      engineering is facilitated by employing the Householder transformation in
      conjunction with discrete supersymmetry. The proposed scheme is general and can
      in principle be used in different platforms such as VCSEL arrays and photonic
      crystal laser arrays.

PMID- 27698354
TI  - Direct-indirect character of the bandgap in methylammonium lead iodide
      perovskite.
AB  - Metal halide perovskites such as methylammonium lead iodide (CH3NH3PbI3) are
      generating great excitement due to their outstanding optoelectronic properties,
      which lend them to application in high-efficiency solar cells and light-emission
      devices. However, there is currently debate over what drives the second-order
      electron-hole recombination in these materials. Here, we propose that the bandgap
      in CH3NH3PbI3 has a direct-indirect character. Time-resolved photo-conductance
      measurements show that generation of free mobile charges is maximized for
      excitation energies just above the indirect bandgap. Furthermore, we find that
      second-order electron-hole recombination of photo-excited charges is retarded at
      lower temperature. These observations are consistent with a slow phonon-assisted
      recombination pathway via the indirect bandgap. Interestingly, in the low
      temperature orthorhombic phase, fast quenching of mobile charges occurs
      independent of the temperature and photon excitation energy. Our work provides a
      new framework to understand the optoelectronic properties of metal halide
      perovskites and analyse spectroscopic data.

PMID- 27698356
TI  - Three representations of the Ising model.
AB  - Statistical models that analyse (pairwise) relations between variables encompass
      assumptions about the underlying mechanism that generated the associations in the
      observed data. In the present paper we demonstrate that three Ising model
      representations exist that, although each proposes a distinct theoretical
      explanation for the observed associations, are mathematically equivalent. This
      equivalence allows the researcher to interpret the results of one model in three
      different ways. We illustrate the ramifications of this by discussing concepts
      that are conceived as problematic in their traditional explanation, yet when
      interpreted in the context of another explanation make immediate sense.

PMID- 27698357
TI  - Impact of high fat diet on long non-coding RNAs and messenger RNAs expression in
      the aortas of ApoE(-/-) mice.
AB  - Atherosclerosis is a chronic multifactorial inflammatory disease with high
      prevalence worldwide, and has become the leading cause of death. The present
      study was designed to investigate the impact of high-fat diet on ApoE(-/-) mice
      exhibiting atherosclerosis by detecting the genome-wide expression profile of
      lncRNAs and mRNAs. A total of 354 differentially expressed lncRNAs were
      identified (>=2.0 folds). Simultaneously, 357 differentially expressed mRNAs from
      the same chip were found. The expression differences of lncRNAs and mRNAs were
      consistent in both qPCR and microarray detection. Annotation results of the mRNAs
      which correlated with lncRNAs showed that the commonly related pathways were
      metabolism and inflammation. Hypergeometric distribution analysis indicated that
      the differentially expressed lncRNAs had been mostly regulated by transcription
      factors (TFs) such as Myod1, Rxra, Pparg, Tcf3, etc. Additional lncRNA-target-TFs
      network analysis was conducted for the top 20 differentially expressed lncRNAs.
      The results indicated Hnf4a, Ppara, Vdr, and Runx3 as the TFs most likely to
      regulate the production of these lncRNAs, and might play roles in inflammatory
      and metabolic processes in atherosclerosis. In a nutshell, the present study
      identified a panel of dysregulated lncRNAs and mRNAs that may be potential
      biomarkers or drug targets relevant to the high-fat diet related atherogenesis.

PMID- 27698359
TI  - Observation of a hybrid state of Tamm plasmons and microcavity exciton
      polaritons.
AB  - We present evidence for the existence of a hybrid state of Tamm plasmons and
      microcavity exciton polaritons in a II-VI material based microcavity sample
      covered with an Ag metal layer. The bare cavity mode shows a characteristic
      anticrossing with the Tamm-plasmon mode, when microreflectivity measurements are
      performed for different detunings between the Tamm plasmon and the cavity mode.
      When the Tamm-plasmon mode is in resonance with the cavity polariton four hybrid
      eigenstates are observed due to the coupling of the cavity-photon mode, the Tamm
      plasmon mode, and the heavy- and light-hole excitons. If the bare Tamm-plasmon
      mode is tuned, these resonances will exhibit three anticrossings. Experimental
      results are in good agreement with calculations based on the transfer matrix
      method as well as on the coupled-oscillators model. The lowest hybrid eigenstate
      is observed to be red shifted by about 13 meV with respect to the lower cavity
      polariton state when the Tamm plasmon is resonantly coupled with the cavity
      polariton. This spectral shift which is caused by the metal layer can be used to
      create a trapping potential channel for the polaritons. Such channels can guide
      the polariton propagation similar to one-dimensional polariton wires.

PMID- 27698358
TI  - In-vivo Imaging of Magnetic Fields Induced by Transcranial Direct Current
      Stimulation (tDCS) in Human Brain using MRI.
AB  - Transcranial direct current stimulation (tDCS) is an emerging non-invasive
      neuromodulation technique that applies mA currents at the scalp to modulate
      cortical excitability. Here, we present a novel magnetic resonance imaging (MRI)
      technique, which detects magnetic fields induced by tDCS currents. This technique
      is based on Ampere's law and exploits the linear relationship between direct
      current and induced magnetic fields. Following validation on a phantom with a
      known path of electric current and induced magnetic field, the proposed MRI
      technique was applied to a human limb (to demonstrate in-vivo feasibility using
      simple biological tissue) and human heads (to demonstrate feasibility in standard
      tDCS applications). The results show that the proposed technique detects tDCS
      induced magnetic fields as small as a nanotesla at millimeter spatial resolution.
      Through measurements of magnetic fields linearly proportional to the applied tDCS
      current, our approach opens a new avenue for direct in-vivo visualization of tDCS
      target engagement.

PMID- 27698360
TI  - Repeated superovulation may affect mitochondrial functions of cumulus cells in
      mice.
AB  - Controlled ovarian stimulation by exogenous gonadotrophins is a key procedure
      during the in vitro fertilization cycle to obtain a sufficient number of oocytes
      in humans. Previous studies demonstrated that repeated superovulation had
      deleterious effects on the ovaries. However, whether repeated superovulation
      adversely affects the mitochondrial functions of cumulus cells remains unclear.
      In this study, mice were divided into three groups: superovulation once (R1);
      superovulation three times (R3), and superovulation five times (R5). We evaluated
      the effects of repeated superovulation on mitochondrial DNA copies (mtDNA) and
      observed decreased mtDNA copies per cell with increasing number of superovulation
      cycles. Further, we investigated the DNA methylation status in exon 2 and the
      mRNA expression level of nuclear-encoded DNA polymerase gamma A (PolgA). The
      results showed that the DNA methylation levels of PolgA in R1 and R5 were
      slightly lower than in R3. Additionally, the altered DNA methylation in PolgA
      coincided with the changes in PolgA expression in cumulus cells. We also found
      that the mRNA expression of COX1, CYTB, ND2, and ND4 was altered by repeated
      superovulation in cumulus cells. Thus, repeated superovulation had adverse
      effects on mitochondrial function.

PMID- 27698361
TI  - Short-term Effects of Risperidone Monotherapy on Spontaneous Brain Activity in
      First-episode Treatment-naive Schizophrenia Patients: A Longitudinal fMRI Study.
AB  - It is unclear whether abnormal spontaneous neural activation patterns found in
      chronic schizophrenia patients (CSP) are part of the pathogenesis of disease,
      consequences of chronic illness, or effects of antipsychotic treatment. We
      performed a longitudinal resting-state functional magnetic resonance imaging
      (fMRI) study in 42 treatment-naive first-episode schizophrenia patients (FESP) at
      baseline and then after 8-weeks of risperidone monotherapy, and compared the
      findings to 38 healthy volunteers. Spontaneous brain activity was quantified
      using the fractional amplitude of low-frequency fluctuations (fALFF) and regional
      homogeneity (ReHo) and compared between patients and controls. Pretreatment,
      patients exhibited higher fALFF in left caudate compared with controls. After
      treatment, patients had elevated fALFF in bilateral putamen and right caudate,
      and increased ReHo in right caudate and left putamen. Greater increase of fALFF
      in the left putamen correlated with less improvement in positive symptoms. Thus,
      abnormalities of spontaneous neural activity in chronic schizophrenia is at least
      partly due to a medication effect. The observed post-treatment increase in
      striatal intrinsic activity may reflect counter-therapeutic functional adaptation
      to dopamine D2 receptor occupancy required for medication effects on psychosis.

PMID- 27698362
TI  - GPR30 regulates diet-induced adiposity in female mice and adipogenesis in vitro.
AB  - Recent studies showed that GPR30, a seven-transmembrane G-protein-coupled
      receptor, is a novel estrogen receptor (ER) that mediates some biological events
      elicited by estrogen in several types of cancer cells. However, its physiological
      or pathological role in vivo is unclear. Here, we show that GPR30 knockout
      (GPRKO) female mice were protected from high-fat diet (HFD)-induced obesity,
      blood glucose intolerance, and insulin resistance. The decreased body weight gain
      in GPRKO female mice is due to the reduction in body fat mass. These effects
      occurred in the absence of significant changes in food intake, intestinal fat
      absorption, triglyceride metabolism, or energy expenditure. However, GPR30 had no
      significant metabolic effects in male mice fed the HFD and both sexes of mice fed
      a chow diet. Further, GPR30 expression levels in fat tissues of WT obese female
      mice were greatly increased, whereas ERalpha and beta expression was not altered.
      Deletion of GPR30 reduced adipogenic differentiation of adipose tissue-derived
      stromal cells. Conversely, activation of GPR30 enhanced adipogenic
      differentiation of 3T3-L1 preadipocytes. These findings provide evidence for the
      first time that GPR30 promotes adipogenesis and therefore the development of
      obesity in female mice exposed to excess fat energy.

PMID- 27698363
TI  - Comparing performance of modern genotype imputation methods in different
      ethnicities.
AB  - A variety of modern software packages are available for genotype imputation
      relying on advanced concepts such as pre-phasing of the target dataset or
      utilization of admixed reference panels. In this study, we performed a
      comprehensive evaluation of the accuracy of modern imputation methods on the
      basis of the publicly available POPRES samples. Good quality genotypes were
      masked and re-imputed by different imputation frameworks: namely MaCH, IMPUTE2,
      MaCH-Minimac, SHAPEIT-IMPUTE2 and MaCH-Admix. Results were compared to evaluate
      the relative merit of pre-phasing and the usage of admixed references. We showed
      that the pre-phasing framework SHAPEIT-IMPUTE2 can overestimate the certainty of
      genotype distributions resulting in the lowest percentage of correctly imputed
      genotypes in our case. MaCH-Minimac performed better than SHAPEIT-IMPUTE2. Pre
      phasing always reduced imputation accuracy. IMPUTE2 and MaCH-Admix, both relying
      on admixed-reference panels, showed comparable results. MaCH showed superior
      results if well-matched references were available (Nei's GST <= 0.010). For small
      to medium datasets, frameworks using genetically closest reference panel are
      recommended if the genetic distance between target and reference data set is
      small. Our results are valid for small to medium data sets. As shown on a larger
      data set of population based German samples, the disadvantage of pre-phasing
      decreases for larger sample sizes.

PMID- 27698364
TI  - Vitamin D Supplementation for Patients with Dry Eye Syndrome Refractory to
      Conventional Treatment.
AB  - This study investigated the effect of vitamin D supplementation in patients with
      dry eye syndrome (DES) refractory to conventional treatment with vitamin D
      deficiency. A total of 105 patients with DES refractory to conventional treatment
      and vitamin D deficiency that was treated with an intramuscular injection of
      cholecalciferol (200,000 IU). Serum 25-hydroxyvitamin D (25(OH)D) levels were
      measured. Eye discomfort was assessed using ocular surface disease index (OSDI)
      and visual analogue pain score (VAS). Tear break-up time (TBUT), fluorescein
      staining score (FSS), eyelid margin hyperemia, and tear secretion test were
      measured before treatment, and 2, 6, and 10 weeks after vitamin D
      supplementation. Mean serum 25(OH)D level was 10.52 +/- 4.61 ng/mL. TBUT, and
      tear secretion test showed an improvement at 2 and 6 weeks after vitamin D
      supplementation compared to pretreatment values (p < 0.05 for all, paired t
      test). Eyelid margin hyperemia and the severity of symptoms showed improvement at
      2, 6, and 10 weeks after vitamin D supplementation (p < 0.05 for all). Compared
      to pre-treatment values, FSS, OSDI and VAS were decreased at 2 weeks (p < 0.05
      for all). In conclusion, vitamin D supplementation is effective and useful in the
      treatment of patients with DES refractory to conventional treatment and with
      vitamin D deficiency.

PMID- 27698365
TI  - Non-invasive modulation of somatosensory evoked potentials by the application of
      static magnetic fields over the primary and supplementary motor cortices.
AB  - This study was performed to investigate the possibility of non-invasive
      modulation of SEPs by the application of transcranial static magnetic field
      stimulation (tSMS) over the primary motor cortex (M1) and supplementary motor
      cortex (SMA), and to measure the strength of the NdFeB magnetic field by using a
      gaussmeter. An NdFeB magnet or a non-magnetic stainless steel cylinder (for sham
      stimulation) was settled on the scalp over M1 and SMA of 14 subjects for periods
      of 15 min. SEPs following right median nerve stimulation were recorded before and
      immediately after, 5 min after, and 10 min after tSMS from sites C3' and F3.
      Amplitudes of the N33 component of SEPs at C3' significantly decreased
      immediately after tSMS over M1 by up to 20%. However, tSMS over the SMA did not
      affect the amplitude of any of the SEP components. At a distance of 2-3 cm (rough
      depth of the cortex), magnetic field strength was in the range of 110-190 mT. Our
      results that tSMS over M1 can reduce the amplitude of SEPs are consistent with
      those of low-frequency repeated TMS and cathodal tDCS studies. Therefore, tSMS
      could be a useful tool for modulating cortical somatosensory processing.

PMID- 27698366
TI  - Histone acetylation dependent energy landscapes in tri-nucleosome revealed by
      residue-resolved molecular simulations.
AB  - Histone tail acetylation is a key epigenetic marker that tends to open chromatin
      folding and activate transcription. Despite intensive studies, precise roles of
      individual lysine acetylation in chromatin folding have only been poorly
      understood. Here, we revealed structural dynamics of tri-nucleosomes with several
      histone tail acetylation states and analyzed histone tail interactions with DNA
      by performing molecular simulations at an unprecedentedly high resolution. We
      found versatile acetylation-dependent landscapes of tri-nucleosome. The H4 and
      H2A tail acetylation reduced the contact between the first and third nucleosomes
      mediated by the histone tails. The H3 tail acetylation reduced its interaction
      with neighboring linker DNAs resulting in increase of the distance between
      consecutive nucleosomes. Notably, two copies of the same histone in a single
      nucleosome have markedly asymmetric interactions with DNAs, suggesting specific
      pattern of nucleosome docking albeit high inherent flexibility. Estimated
      transcription factor accessibility was significantly high for the H4 tail
      acetylated structures.

PMID- 27698367
TI  - MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up
      regulated in human multiple sclerosis.
AB  - In the mature central nervous system (CNS), oligodendrocytes provide support and
      insulation to axons thanks to the production of a myelin sheath. During their
      maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very
      precise differentiation program, which is finely orchestrated by transcription
      factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding
      RNAs involved in post-transcriptional regulation. Any alterations in this program
      can potentially contribute to dysregulated myelination, impaired remyelination
      and neurodegenerative conditions, as it happens in multiple sclerosis (MS). Here,
      we identify miR-125a-3p, a developmentally regulated miRNA, as a new actor of
      oligodendroglial maturation, that, in the mammalian CNS regulates the expression
      of myelin genes by simultaneously acting on several of its already validated
      targets. In cultured OPCs, over-expression of miR-125a-3p by mimic treatment
      impairs while its inhibition with an antago-miR stimulates oligodendroglial
      maturation. Moreover, we show that miR-125a-3p levels are abnormally high in the
      cerebrospinal fluid of MS patients bearing active demyelinating lesions,
      suggesting that its pathological upregulation may contribute to MS development,
      at least in part by blockade of OPC differentiation leading to impaired repair of
      demyelinated lesions.

PMID- 27698368
TI  - "RaMassays": Synergistic Enhancement of Plasmon-Free Raman Scattering and Mass
      Spectrometry for Multimodal Analysis of Small Molecules.
AB  - SiO2/TiO2 core/shell (T-rex) beads were exploited as "all-in-one" building-block
      materials to create analytical assays that combine plasmon-free surface enhanced
      Raman scattering (SERS) and surface assisted laser desorption/ionization (SALDI)
      mass spectrometry (RaMassays). Such a multi-modal approach relies on the unique
      optical properties of T-rex beads, which are able to harvest and manage light in
      both UV and Vis range, making ionization and Raman scattering more efficient.
      RaMassays were successfully applied to the detection of small (molecular weight,
      M.W. <400 Da) molecules with a key relevance in biochemistry and pharmaceutical
      analysis. Caffeine and cocaine were utilized as molecular probes to test the
      combined SERS/SALDI response of RaMassays, showing excellent sensitivity and
      reproducibility. The differentiation between amphetamine/ephedrine and
      theophylline/theobromine couples demonstrated the synergistic reciprocal
      reinforcement of SERS and SALDI. Finally, the conversion of L-tyrosine in L-DOPA
      was utilized to probe RaMassays as analytical tools for characterizing reaction
      intermediates without introducing any spurious effects. RaMassays exhibit
      important advantages over plasmonic nanoparticles in terms of reproducibility,
      absence of interference and potential integration in multiplexed devices.

PMID- 27698369
TI  - Smartphone-Based Accurate Analysis of Retinal Vasculature towards Point-of-Care
      Diagnostics.
AB  - Retinal vasculature analysis is important for the early diagnostics of various
      eye and systemic diseases, making it a potentially useful biomarker, especially
      for resource-limited regions and countries. Here we developed a smartphone-based
      retinal image analysis system for point-of-care diagnostics that is able to load
      a fundus image, segment retinal vessels, analyze individual vessel width, and
      store or uplink results. The proposed system was not only evaluated on widely
      used public databases and compared with the state-of-the-art methods, but also
      validated on clinical images directly acquired with a smartphone. An Android app
      is also developed to facilitate on-site application of the proposed methods. Both
      visual assessment and quantitative assessment showed that the proposed methods
      achieved comparable results to the state-of-the-art methods that require high
      standard workstations. The proposed system holds great potential for the early
      diagnostics of various diseases, such as diabetic retinopathy, for resource
      limited regions and countries.

PMID- 27698371
TI  - TM4 of the glutamate transporter GLT-1 experiences substrate-induced motion
      during the transport cycle.
AB  - Excitatory amino acid transporter 2 (EAAT2), also known as glial glutamate
      transporter type 1 (GLT-1), plays an important role in maintaining the
      extracellular glutamate concentrations below neurotoxic levels. The highly
      conserved TM2 transmembrane domain of GLT-1 maintains a stable position during
      the transport cycle; however, the effect of the transport cycle on the topology
      of TM4 in not well established. To further reveal the function of TM4, two
      cysteine pairs between TM2 and TM4 were introduced using site-directed
      mutagenesis. A significant decrease of transport activity was observed in the
      I93C/V241C and I97C/V241C mutants upon application of the oxidative cross-linking
      reagent, copper (II) (1,10-phenanthroline)3 (CuPh), which suggests that a
      conformational shift is essential for transporter activity. Furthermore, the
      decrease in activity by CuPh crosslinking was enhanced in external media with
      glutamate or potassium, which suggests that TM2 and TM4 assume closer proximity
      in the inward-facing conformation of the transporter. Our results suggest that
      the TM4 domain of GLT-1, and potentially other glutamate transporters, undergoes
      a complex conformational shift during substrate translocation, which involves an
      increase in the proximity of the TM2 and TM4 domains in the inward-facing
      conformation.

PMID- 27698372
TI  - Bimodal Control of Heat Transport at Graphene-Metal Interfaces Using Disorder in
      Graphene.
AB  - Thermal energy transport across the interfaces of physically and chemically
      modified graphene with two metals, Al and Cu, was investigated by measuring
      thermal conductance using the time-domain thermoreflectance method. Graphene was
      processed using a He2+ ion-beam with a Gaussian distribution or by exposure to
      ultraviolet/O3, which generates structural or chemical disorder, respectively.
      Hereby, we could monitor changes in the thermal conductance in response to
      varying degrees of disorder. We find that the measured conductance increases as
      the density of the physical disorder increases, but undergoes an abrupt
      modulation with increasing degrees of chemical modification, which decreases at
      first and then increases considerably. Moreover, we find that the conductance
      varies inverse proportionally to the average distance between the structural
      defects in the graphene, implying a strong in-plane influence of phonon kinetics
      on interfacial heat flow. We attribute the bimodal results to an interplay
      between the distinct effects on graphene's vibrational modes exerted by graphene
      modification and by the scattering of modes.

PMID- 27698370
TI  - Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide
      Ameliorates Experimental Uremic Cardiomyopathy.
AB  - We have previously reported that the sodium potassium adenosine triphosphatase
      (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this
      study, we examined whether attenuation of oxidant stress by antagonism of Na/K
      ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy
      induced by partial nephrectomy (PNx). PNx induced the development of cardiac
      morphological and biochemical changes consistent with human uremic
      cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with
      pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin
      (CoPP) markedly attenuated the development of phenotypical features of uremic
      cardiomyopathy. In a reversal study, administration of pNaKtide after the
      induction of uremic cardiomyopathy reversed many of the phenotypical features.
      Attenuation of Na/K-ATPase oxidant amplification may be a potential strategy for
      clinical therapy of this disorder.

PMID- 27698373
TI  - Identification of drought-responsive microRNAs and their targets in
      Ammopiptanthus mongolicus by using high-throughput sequencing.
AB  - MicroRNAs (miRNAs) regulate target gene expression to modulate plant growth,
      development, and biotic and abiotic stress response at the post-transcriptional
      level. Ammopiptanthus mongolicus, an ecologically important desert plant, is
      increasingly used as a model for studying stress tolerance in plants. The miRNA
      mediated gene regulatory network might remarkably contribute to the high stress
      tolerance of A. mongolicus. However, a genome-wide identification of miRNAs and
      their targets is still lacking in A. mongolicus. In this study, 170 conserved and
      156 non-conserved miRNAs were identified in A. mongolicus. We experimentally
      identified 298 miRNA-target pairs from the degradome data. Quantitative real-time
      polymerase chain reaction analyses identified 28 drought-responsive miRNAs in
      leaves and 15 in roots. Some characteristics of the miRNA-mediated regulatory
      network were found in A. mongolicus. Multiple miRNAs, including 2 newly
      identified non-conserved miRNAs, miR-P11 and miR-P14, generated from the
      precursors of miR169, were found to be involved in drought stress response.
      Further, miR2118 and miR858 participated in drought stress response by up
      regulating OZF1 gene and certain MYB genes that were involved in the regulation
      of flavonol biosynthesis in A. mongolicus. The findings of this study might
      provide new insights for understanding the functions of miRNA in stress response
      in plants.

PMID- 27698374
TI  - Sleep duration, daytime napping, markers of obstructive sleep apnea and stroke in
      a population of southern China.
AB  - Sleep habits are associated with stroke in western populations, but this relation
      has been rarely investigated in China. Moreover, the differences among stroke
      subtypes remain unclear. This study aimed to explore the associations of total
      stroke, including ischemic and hemorrhagic type, with sleep habits of a
      population in southern China. We performed a case-control study in patients
      admitted to the hospital with first stroke and community control subjects. A
      total of 333 patients (n = 223, 67.0%, with ischemic stroke; n = 110, 23.0%, with
      hemorrhagic stroke) and 547 controls were enrolled in the study. Participants
      completed a structured questionnaire to identify sleep habits and other stroke
      risk factors. Least absolute shrinkage and selection operator (Lasso) and
      multiple logistic regression were performed to identify risk factors of disease.
      Incidence of stroke, and its subtypes, was significantly associated with
      snorting/gasping, snoring, sleep duration, and daytime napping. Snorting/gasping
      was identified as an important risk factor in the Lasso logistic regression model
      (Lasso' beta = 0.84), and the result was proven to be robust. This study showed
      the association between stroke and sleep habits in the southern Chinese
      population and might help in better detecting important sleep-related factors for
      stroke risk.

PMID- 27698375
TI  - Microfluidic cantilever detects bacteria and measures their susceptibility to
      antibiotics in small confined volumes.
AB  - In the fight against drug-resistant bacteria, accurate and high-throughput
      detection is essential. Here, a bimaterial microcantilever with an embedded
      microfluidic channel with internal surfaces chemically or physically
      functionalized with receptors selectively captures the bacteria passing through
      the channel. Bacterial adsorption inside the cantilever results in changes in the
      resonance frequency (mass) and cantilever deflection (adsorption stress). The
      excitation of trapped bacteria using infrared radiation (IR) causes the
      cantilever to deflect in proportion to the infrared absorption of the bacteria,
      providing a nanomechanical infrared spectrum for selective identification. We
      demonstrate the in situ detection and discrimination of Listeria monocytogenes at
      a concentration of single cell per MUl. Trapped Escherichia coli in the
      microchannel shows a distinct nanomechanical response when exposed to
      antibiotics. This approach, which combines enrichment with three different modes
      of detection, can serve as a platform for the development of a portable, high
      throughput device for use in the real-time detection of bacteria and their
      response to antibiotics.

PMID- 27698376
TI  - Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma
      and the toxicity-reducing effect of processing.
AB  - Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been
      frequently reported about its toxicity. According to the traditional Chinese
      medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to
      determine if processing reduces the toxicity of raw PR, and to explore the
      underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing
      effect of processing. Biochemical and histopathological approaches were used to
      evaluate the toxicities of raw and processed PR. Rat serum metabolites were
      analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data
      highlighted the biological pathways and network functions involved in raw PR
      induced toxicities and the toxicity-reducing effect of processing, which were
      verified by molecular approaches. Results showed that raw PR caused
      cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling
      and activation of the TGF-beta pathway contributed to raw PR-induced
      cardiotoxicity, and free radical scavenging might be responsible for the toxicity
      reducing effect of processing. Our data shed new light on the mechanisms of raw
      PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This
      study provides scientific justifications for the traditional processing theory of
      PR, and should help in optimizing the processing protocol and clinical
      combinational application of PR.

PMID- 27698378
TI  - Characterization of a very rare case of living ewe-buck hybrid using classical
      and molecular cytogenetics.
AB  - The natural occurrence of live hybrid offsprings between sheep and goats has been
      documented in literature, however all the studies have reported the mating of
      goats with rams, whereas the reciprocal cross was never documented. This study
      reports on a very rare case of interspecies hybridization occurred between a ewe
      (2n = 54, XX) and a buck (2n = 60, XY). The hybrid, born in a German flock under
      natural conditions, is characterised by an intermediate karyotype (2n = 57, XX).
      The CBA-banding has shown 3 metacentric and 54 acrocentric chromosomes, whereas
      the GTG- and RBA-banding have revealed that the autosomes involved in the hybrid
      combination were CHI1, 3; CHI2, 8 and CHI5, 11 corresponding to the metacentric
      chromosomes OAR1, OAR2 and OAR3. A tri-colour FISH using chromosome paintings and
      BAC probes has validated this arrangement. A further FISH analysis has been
      carried out to analyse the telomeres, which showed a normal structure. Nucleolus
      organiser-bearing chromosomes were identified as pairs OAR1p(CHI3), OAR2q(CHI2),
      OAR3q(CHI5), OAR4(CHI4) and OAR25(CHI28), and nuclear associations were found.
      Sex chromosomes were correctly arranged. The odd number of the karyotype might be
      responsible for a reduced fertility as consequence of the incorrect chromosomal
      pairing and/or segregation during the meiosis.

PMID- 27698379
TI  - Tunable sound transmission at an impedance-mismatched fluidic interface assisted
      by a composite waveguide.
AB  - We report a composite waveguide fabricated by attaching a coupling aperture to a
      waveguide. The acoustic impedance of the composite waveguide can be regulated by
      merely controlling its coupling vibrations, depending on its structure size. By
      changing the size to adjust the acoustic impedance of the composite waveguide at
      an impedance-mismatched fluidic interface, tunable sound transmission at the
      desired frequencies is achieved. The reported composite waveguide provides a new
      method for sound regulation at a mismatched fluidic interface and has extensive
      frequency hopping and frequency agility applications in air-water sound
      communication.

PMID- 27698377
TI  - Inhibition of Complement Retards Ankylosing Spondylitis Progression.
AB  - Ankylosing spondylitis (AS) is a chronic axial spondyloarthritis (SpA) resulting
      in back pain and progressive spinal ankyloses. Currently, there are no effective
      therapeutics targeting AS largely due to elusive pathogenesis mechanisms, even as
      potential candidates such as HLA-B27 autoantigen have been identified. Herein, we
      employed a proteoglycan (PG)-induced AS mouse model together with clinical
      specimens, and found that the complement system was substantially activated in
      the spinal bone marrow, accompanied by a remarkable proportion alteration of
      neutrophils and macrophage in bone marrow and spleen, and by the significant
      increase of TGF-beta1 in serum. The combined treatment with a bacteria-derived
      complement inhibitor Efb-C (C-terminal of extracellular fibrinogen-binding
      protein of Staphylococcus aureus) remarkably retarded the progression of mouse AS
      by reducing osteoblast differentiation. Furthermore, we demonstrated that two
      important modulators involved in AS disease, TGF-beta1 and RANKL, were elevated
      upon in vitro complement attack in osteoblast and/or osteoclast cells. These
      findings further unravel that complement activation is closely related with the
      pathogenesis of AS, and suggest that complement inhibition may hold great
      potential for AS therapy.

PMID- 27698380
TI  - Survival Motor Neuron (SMN) protein is required for normal mouse liver
      development.
AB  - Spinal Muscular Atrophy (SMA) is caused by mutation or deletion of the survival
      motor neuron 1 (SMN1) gene. Decreased levels of, cell-ubiquitous, SMN protein is
      associated with a range of systemic pathologies reported in severe patients.
      Despite high levels of SMN protein in normal liver, there is no comprehensive
      study of liver pathology in SMA. We describe failed liver development in response
      to reduced SMN levels, in a mouse model of severe SMA. The SMA liver is dark red,
      small and has: iron deposition; immature sinusoids congested with blood;
      persistent erythropoietic elements and increased immature red blood cells;
      increased and persistent megakaryocytes which release high levels of platelets
      found as clot-like accumulations in the heart. Myelopoiesis in contrast, was
      unaffected. Further analysis revealed significant molecular changes in SMA liver,
      consistent with the morphological findings. Antisense treatment from birth with
      PMO25, increased lifespan and ameliorated all morphological defects in liver by
      postnatal day 21. Defects in the liver are evident at birth, prior to motor
      system pathology, and impair essential liver function in SMA. Liver is a key
      recipient of SMA therapies, and systemically delivered antisense treatment,
      completely rescued liver pathology. Liver therefore, represents an important
      therapeutic target in SMA.

PMID- 27698382
TI  - Lichen elemental composition distinguishes anthropogenic emissions from dust
      storm inputs and differs among species: Evidence from Xilinhot, Inner Mongolia,
      China.
AB  - To test the applicability of lichens in the biomonitoring of atmospheric
      elemental deposition in a typical steppe zone of Inner Mongolia, China, six
      foliose lichens (Physcia aipolia, PA; P. tribacia, PT; Xanthoria elegans, XE; X.
      mandschurica, XM; Xanthoparmelia camtschadalis, XPC; and Xp. tinctina, XPT) were
      sampled from the Xilin River Basin, Xilinhot, Inner Mongolia, China. Twenty-five
      elements (Al, Ba, Cd, Ce, Cr, Cs, Cu, Fe, K, La, Mn, Mo, Na, Ni, P, Pb, Sb, Sc,
      Sm, Tb, Th, Ti, Tl, V and Zn) in the lichens were analysed using inductively
      coupled plasma mass spectrometry (ICP-MS). The results show that Cd, Pb and Zn
      were mainly atmospheric in origin, whereas the other elements were predominantly
      of crustal origin. Compared with other studies, our data were higher in crustal
      element concentrations and lower in atmospheric element concentrations, matching
      with the frequent, severe dust storms and road traffic in the area. The elemental
      concentrations in lichens are both species- and element-specific, highlighting
      the importance of species selection for biomonitoring air pollution using
      lichens. We recommend PT, XE, XM and XPT for monitoring atmospheric deposition of
      crustal elements; XPC and XPT for Cd and Pb; PA for Cd and Zn; and PT for Cd.

PMID- 27698381
TI  - The shift of microbial communities and their roles in sulfur and iron cycling in
      a copper ore bioleaching system.
AB  - Bioleaching has been employed commercially to recover metals from low grade ores,
      but the production efficiency remains to be improved due to limited understanding
      of the system. This study examined the shift of microbial communities and S&Fe
      cycling in three subsystems within a copper ore bioleaching system: leaching heap
      (LH), leaching solution (LS) and sediment under LS. Results showed that both LH
      and LS had higher relative abundance of S and Fe oxidizing bacteria, while S and
      Fe reducing bacteria were more abundant in the Sediment. GeoChip analysis showed
      a stronger functional potential for S0 oxidation in LH microbial communities.
      These findings were consistent with measured oxidation activities to S0 and Fe2+,
      which were highest by microbial communities from LH, lower by those from LS and
      lowest form Sediment. Moreover, phylogenetic molecular ecological network
      analysis indicated that these differences might be related to interactions among
      microbial taxa. Last but not the least, a conceptual model was proposed, linking
      the S&Fe cycling with responsible microbial populations in the bioleaching
      systems. Collectively, this study revealed the microbial community and functional
      structures in all three subsystems of the copper ore, and advanced a holistic
      understanding of the whole bioleaching system.

PMID- 27698384
TI  - Comparative Secretome Analysis Reveals Perturbation of Host Secretion Pathways by
      a Hypovirus.
AB  - To understand the impact of a hypovirus infection on the secretome of the
      chestnut blight fungus, Cryphonectria parasitica, a phytopathogenic filamentous
      fungus, two-dimensional electrophoresis (2-DE) and isobaric tag for relative and
      absolute quantitation (iTRAQ) technology were employed to identify and quantify
      the secreted proteins. A total of 403 unique proteins were identified from the
      secretome of the wild type virus-free strain EP155. Of these proteins, 329 were
      predicted to be involved in known secretory pathways and they are primarily
      composed of metabolic enzymes, biological regulators, responders to stimulus and
      components involved in plant-pathogen interactions. When infected with the
      hypovirus CHV1-EP713, 99 proteins were found to be differentially expressed as
      compared to the wild type strain EP155. These proteins were mainly related to
      plant cell wall degradation, response to host defense, fungal virulence and
      intracellular structure. The effects of CHV1 on secreted proteins may reveal a
      relationship between physiological pathways and hypovirulence.

PMID- 27698386
TI  - High-Resolution Impedance Manometry Metrics of the Esophagogastric Junction for
      the Assessment of Treatment Response in Achalasia.
AB  - OBJECTIVES: We aimed to evaluate the value of novel high-resolution impedance
      manometry (HRIM) metrics, bolus flow time (BFT), and esophagogastric junction
      (EGJ) contractile integral (CI), as well as EGJ pressure (EGJP) and the
      integrated relaxation pressure (IRP), as indicators of treatment response in
      achalasia. METHODS: We prospectively evaluated 75 patients (ages 19-81, 32
      female) with achalasia during follow-up after pneumatic dilation or myotomy with
      Eckardt score (ES), timed-barium esophagram (TBE), and HRIM. Receiver-operating
      characteristic (ROC) curves for good symptomatic outcome (ES<=3) and good
      radiographic outcome (TBE column height at 5 min<5 cm) were generated for each
      potential predictor of treatment response (EGJP, IRP, BFT, and EGJ-CI). RESULTS:
      Follow-up occurred at a median (range) 12 (3-291) months following treatment. A
      total of 49 patients had good symptomatic outcome and 46 had good radiographic
      outcome. The area-under-the-curves (AUCs) on the ROC curve for symptomatic
      outcome were 0.55 (EGJP), 0.62 (IRP), 0.77 (BFT) and 0.56 (EGJ-CI). The AUCs for
      radiographic outcome were 0.64 (EGJP), 0.48 (IRP), 0.73 (BFT), and 0.65 (EGJ-CI).
      Optimal cut-points were determined as 11 mm Hg (EGJP), 12 mm Hg (IRP), 0 s (BFT),
      and 30 mm Hg*cm (EGJ-CI) that provided sensitivities/specificities of 57%/46%
      (EGJP), 65%/58% (IRP), 78%/77% (BFT), and 53%/62% (EGJ-CI) to predict symptomatic
      outcome and 57%/66% (EGJP), 57%/41% (IRP), 76%/69% (BFT), and 57%/66% (EGJ-CI) to
      predict radiographic outcome. CONCLUSIONS: BFT, a novel HRIM metric, provided an
      improved functional assessment over manometric measures of EGJP, IRP, and EGJ-CI
      at follow-up after achalasia treatment and may help direct clinical management.

PMID- 27698383
TI  - Outer membrane vesicles from flagellin-deficient Salmonella enterica serovar
      Typhimurium induce cross-reactive immunity and provide cross-protection against
      heterologous Salmonella challenge.
AB  - Outer membrane vesicles (OMVs) isolated from Salmonella Typhimurium are
      potentially useful for developing subunit vaccines because of high immunogenicity
      and protective efficacy. However, flagella might remain in OMV pellets following
      OMV purification, resulting in non-essential immune responses and counteraction
      of bacterial protective immune responses when developing a vaccine against
      infection of multiple serotypes Salmonella. In this study, a flagellin-deficient
      S. Typhimurium mutant was constructed. Lipopolysaccharide profiles, protein
      profiles and cryo-electron microscopy revealed that there were no significant
      differences between the wild-type and mutant OMVs, with the exception of a large
      amount of flagellin in the wild-type OMVs. Neither the wild-type OMVs nor the non
      flagellin OMVs were toxic to macrophages. Mice immunized with the non-flagellin
      OMVs produced high concentrations of IgG. The non-flagellin OMVs elicited strong
      mucosal antibody responses in mice when administered via the intranasal route in
      addition to provoking higher cross-reactive immune responses against OMPs
      isolated from S. Choleraesuis and S. Enteritidis. Both intranasal and
      intraperitoneal immunization with the non-flagellin OMVs provided efficient
      protection against heterologous S. Choleraesuis and S. Enteritidis challenge. Our
      results indicate that the flagellin-deficient OMVs may represent a new vaccine
      platform that could be exploited to facilitate the production of a broadly
      protective vaccine.

PMID- 27698387
TI  - Negative Is Positive.

PMID- 27698385
TI  - Photodynamic N-TiO2 Nanoparticle Treatment Induces Controlled ROS-mediated
      Autophagy and Terminal Differentiation of Leukemia Cells.
AB  - In this study, we used nitrogen-doped titanium dioxide (N-TiO2) NPs in
      conjugation with visible light, and show that both reactive oxygen species (ROS)
      and autophagy are induced by this novel NP-based photodynamic therapy (PDT)
      system. While well-dispersed N-TiO2 NPs (<=100 MUg/ml) were inert, their photo
      activation with visible light led to ROS-mediated autophagy in leukemia K562
      cells and normal peripheral lymphocytes, and this increased in parallel with
      increasing NP concentrations and light doses. At a constant light energy (12
      J/cm2), increasing N-TiO2 NP concentrations increased ROS levels to trigger
      autophagy-dependent megakaryocytic terminal differentiation in K562 cells. By
      contrast, an ROS challenge induced by high N-TiO2 NP concentrations led to
      autophagy-associated apoptotic cell death. Using chemical autophagy inhibitors (3
      methyladenine and Bafilomycin A1), we confirmed that autophagy is required for
      both terminal differentiation and apoptosis induced by photo-activated N-TiO2.
      Pre-incubation of leukemic cells with ROS scavengers muted the effect of N-TiO2
      NP-based PDT on cell fate, highlighting the upstream role of ROS in our system.
      In summary, PDT using N-TiO2 NPs provides an effective method of priming
      autophagy by ROS induction. The capability of photo-activated N-TiO2 NPs in
      obtaining desirable cellular outcomes represents a novel therapeutic strategy of
      cancer cells.

PMID- 27698388
TI  - The variances of Sp1 and NF-kappaB elements correlate with the greater capacity
      of Chinese HIV-1 B'-LTR for driving gene expression.
AB  - The 5' end of HIV-1 long terminal repeat (LTR) serves as a promoter that plays an
      essential role in driving viral gene transcription. Manipulation of HIV-1 LTR
      provides a potential therapeutic strategy for suppressing viral gene expression
      or excising integrated provirus. Subtype-specific genetic diversity in the LTR
      region has been observed. The minor variance of LTR, particularly in the
      transcription factor binding sites, can have a profound impact on its activity.
      However, the LTR profiles from major endemic Chinese subtypes are not well
      characterized. Here, by characterizing the sequences and functions of LTRs from
      endemic Chinese HIV-1 subtypes, we showed that nucleotide variances of Sp1 core
      promoter and NF-kappaB element are associated with varied LTR capacity for
      driving viral gene transcription. The greater responsiveness of Chinese HIV-1 B'
      LTR for driving viral gene transcription upon stimulation is associated with an
      increased level of viral reactivation. Moreover, we demonstrated that the
      introduction of CRISPR/dead Cas9 targeting Sp1 or NF-kappaB element suppressed
      viral gene expression. Taken together, our study characterized LTRs from endemic
      HIV-1 subtypes in China and suggests a potential target for the suppression of
      viral gene expression and a novel strategy that facilitates the accomplishment of
      a functional cure.

PMID- 27698389
TI  - Aldo-keto reductase 1C1 induced by interleukin-1beta mediates the invasive
      potential and drug resistance of metastatic bladder cancer cells.
AB  - In treating bladder cancer, determining the molecular mechanisms of tumor
      invasion, metastasis, and drug resistance are urgent to improving long-term
      patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1),
      plays an essential role in cancer invasion/metastasis and chemoresistance. In
      orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3,
      metastatic sublines were established from tumors in the liver, lung, and bone.
      These cells possessed elevated levels of EMT-associated markers, such as Snail,
      Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1
      was found to be up-regulated in metastatic lesions, which was verified in
      metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1
      knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably
      due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin
      1beta, was found to increase AKR1C1 in bladder cancer cell lines. One particular
      non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and
      decreased the cisplatin-resistance and invasion potential of metastatic sublines.
      These data uncover the crucial role of AKR1C1 in regulating both metastasis and
      drug resistance; as a result, AKR1C1 should be a potent molecular target in
      invasive bladder cancer treatment.

PMID- 27698390
TI  - ProQ3: Improved model quality assessments using Rosetta energy terms.
AB  - Quality assessment of protein models using no other information than the
      structure of the model itself has been shown to be useful for structure
      prediction. Here, we introduce two novel methods, ProQRosFA and ProQRosCen,
      inspired by the state-of-art method ProQ2, but using a completely different
      description of a protein model. ProQ2 uses contacts and other features calculated
      from a model, while the new predictors are based on Rosetta energies: ProQRosFA
      uses the full-atom energy function that takes into account all atoms, while
      ProQRosCen uses the coarse-grained centroid energy function. The two new
      predictors also include residue conservation and terms corresponding to the
      agreement of a model with predicted secondary structure and surface area, as in
      ProQ2. We show that the performance of these predictors is on par with ProQ2 and
      significantly better than all other model quality assessment programs.
      Furthermore, we show that combining the input features from all three predictors,
      the resulting predictor ProQ3 performs better than any of the individual methods.
      ProQ3, ProQRosFA and ProQRosCen are freely available both as a webserver and
      stand-alone programs at http://proq3.bioinfo.se/.

PMID- 27698391
TI  - A crucial role for spatial distribution in bacterial quorum sensing.
AB  - Quorum sensing (QS) is a process that enables bacteria to communicate using
      secreted signaling molecules, and then makes a population of bacteria to regulate
      gene expression collectively and control behavior on a community-wide scale.
      Theoretical studies of efficiency sensing have suggested that both mass-transfer
      performance in the local environment and the spatial distribution of cells are
      key factors affecting QS. Here, an experimental model based on hydrogel
      microcapsules with a three-dimensional structure was established to investigate
      the influence of the spatial distribution of cells on bacterial QS. Vibrio
      harveyi cells formed different spatial distributions in the microcapsules, i.e.,
      they formed cell aggregates with different structures and sizes. The cell
      aggregates displayed stronger QS than did unaggregated cells even when equal
      numbers of cells were present. Large aggregates (LA) of cells, with a size of
      approximately 25 MUm, restricted many more autoinducers (AIs) than did small
      aggregates (SA), with a size of approximately 10 MUm, thus demonstrating that
      aggregate size significantly affects QS. These findings provide a powerful
      demonstration of the fact that the spatial distribution of cells plays a crucial
      role in bacterial QS.

PMID- 27698392
TI  - Haptic adaptation to slant: No transfer between exploration modes.
AB  - Human touch is an inherently active sense: to estimate an object's shape humans
      often move their hand across its surface. This way the object is sampled both in
      a serial (sampling different parts of the object across time) and parallel
      fashion (sampling using different parts of the hand simultaneously). Both the
      serial (moving a single finger) and parallel (static contact with the entire
      hand) exploration modes provide reliable and similar global shape information,
      suggesting the possibility that this information is shared early in the sensory
      cortex. In contrast, we here show the opposite. Using an adaptation-and-transfer
      paradigm, a change in haptic perception was induced by slant-adaptation using
      either the serial or parallel exploration mode. A unified shape-based coding
      would predict that this would equally affect perception using other exploration
      modes. However, we found that adaptation-induced perceptual changes did not
      transfer between exploration modes. Instead, serial and parallel exploration
      components adapted simultaneously, but to different kinaesthetic aspects of
      exploration behaviour rather than object-shape per se. These results indicate
      that a potential combination of information from different exploration modes can
      only occur at down-stream cortical processing stages, at which adaptation is no
      longer effective.

PMID- 27698393
TI  - Tunable Surface Plasmon and Phonon Polariton Interactions for Moderately Doped
      Semiconductor Surfaces.
AB  - Spatial charge distribution for biased semiconductors fundamentally differs from
      metals since they can allow inhomogeneous charge distributions due to penetration
      of the electric field, as observed in the classical Schottky junctions.
      Similarly, the electrostatics of the dielectric/semiconductor interface can lead
      to a carrier depletion or accumulation in the semiconductor side when under
      applied bias. In this study, we demonstrate that the inhomogeneous carrier
      accumulation in a moderately p-doped GaAs-dielectric interface can be tailored
      for tunable plasmonics by an external voltage. Solving Maxwell's equations in the
      doped GaAs-dielectric stack, we investigate the tunability of the surface plasmon
      and phonon polaritons' interaction via an external bias. The plasmonic mode
      analysis of such an interface reveals interesting dispersion curves for surface
      plasmon and phonon polariton interactions that are not possible in metals. We
      show that the plasmon dispersion curve can be engineered through an external bias
      using the inherent properties of the p-doped GaAs- dielectric interface.

PMID- 27698394
TI  - The pioneering role of PRDM9 indel mutations in tarsier evolution.
AB  - PRDM9 is currently the sole speciation gene found in vertebrates causing hybrid
      sterility probably due to incompatible alleles. Its role in defining the double
      strand break loci during the meiotic prophase I is crucial for proper chromosome
      segregation. Therefore, the rapid turnover of the loci determining zinc finger
      array seems to be causative for incompatibilities. We here investigated the zinc
      finger domain-containing exon of PRDM9 in 23 tarsiers. Tarsiers, the most basal
      extant haplorhine primates, exhibit two frameshifting indels at the 5'-end of the
      array. The first mutation event interrupts the reading frame and function while
      the second compensates both. The fixation of this allele variant in tarsiers led
      to hypothesize that de- and reactivation of the zinc finger domain drove the
      speciation in early haplorhine or tarsiiform primates. Moreover, the high allelic
      diversity within Tarsius points to multiple effects of genetic drift reflecting
      their phylogeographic history since the Miocene.

PMID- 27698397
TI  - Testicular cancer: Genetic determinants of cisplatin resistance.

PMID- 27698395
TI  - Hierarchical phosphorylation of apical membrane antigen 1 is required for
      efficient red blood cell invasion by malaria parasites.
AB  - Central to the pathogenesis of malaria is the proliferation of Plasmodium
      falciparum parasites within human erythrocytes. Parasites invade erythrocytes via
      a coordinated sequence of receptor-ligand interactions between the parasite and
      host cell. One key ligand, Apical Membrane Antigen 1 (AMA1), is a leading blood
      stage vaccine and previous work indicates that phosphorylation of its cytoplasmic
      domain (CPD) is important to its function during invasion. Here we investigate
      the significance of each of the six available phospho-sites in the CPD. We
      confirm that the cyclic AMP/protein kinase A (PKA) signalling pathway elicits a
      phospho-priming step upon serine 610 (S610), which enables subsequent
      phosphorylation in vitro of a conserved, downstream threonine residue (T613) by
      glycogen synthase kinase 3 (GSK3). Both phosphorylation steps are required for
      AMA1 to function efficiently during invasion. This provides the first evidence
      that the functions of key invasion ligands of the malaria parasite are regulated
      by sequential phosphorylation steps.

PMID- 27698396
TI  - The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by
      Mycobacterium tuberculosis PtpA during mycobacterial infection.
AB  - Macrophage-mediated innate immune responses play crucial roles in host defense
      against pathogens. Recent years have seen an explosion of host proteins that act
      as restriction factors blocking viral replication in infected cells. However, the
      essential factors restricting Mycobacterium tuberculosis (Mtb) and their
      regulatory roles during mycobacterial infection remain largely unknown. We
      previously reported that Mtb tyrosine phosphatase PtpA, a secreted effector
      protein required for intracellular survival of Mtb, inhibits innate immunity by
      co-opting the host ubiquitin system. Here, we identified a new PtpA-interacting
      host protein TRIM27, which is reported to possess a conserved RING domain and
      usually acts as an E3 ubiquitin ligase that interferes with various cellular
      processes. We further demonstrated that TRIM27 restricts survival of mycobacteria
      in macrophages by promoting innate immune responses and cell apoptosis.
      Interestingly, Mtb PtpA could antagonize TRIM27-promoted JNK/p38 MAPK pathway
      activation and cell apoptosis through competitively binding to the RING domain of
      TRIM27. TRIM27 probably works as a potential restriction factor for Mtb and its
      function is counteracted by Mtb effector proteins such as PtpA. Our study
      suggests a potential tuberculosis treatment via targeting of the TRIM27-PtpA
      interfaces.

PMID- 27698398
TI  - Regenerative medicine: Isolation of nephron progenitors: a step towards growing
      kidneys?

PMID- 27698399
TI  - Kidney cancer: On target - inhibiting SPOP in ccRCC.

PMID- 27698400
TI  - Evaluation of dusting versus basketing - can new technologies improve stone-free
      rates?
AB  - Over the past two decades, the management of upper-tract urinary stones has
      dramatically changed towards an increase in the use of ureteroscopic treatment.
      This change has been driven by technological advances such as the creation of
      flexible ureteroscopes with reduced calibre (which now have digital, disposable
      and dual flexion capability) and holmium lasers with increased power. Two basic
      principles exist when treating stones ureteroscopically: either creating stone
      dust and small fragments (<1-2 mm) to theoretically enable spontaneous passage of
      the small particles or stone fragmentation that enables safe extraction of the
      stone pieces with a basket or grasper in an efficient manner. Each method has
      unique advantages and disadvantages, but, ultimately, surgeon preference, stone
      size, composition, location and intrarenal and/or ureteral anatomy determine
      which technique is used. To date, clinical trials comparing these two techniques
      are lacking.

PMID- 27698401
TI  - Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to
      anti-TNF treatment in rheumatoid arthritis.
AB  - Several genetic variants in Toll-like receptor (TLR) and nuclear factor (NF)
      kappaB signalling pathways have been reported associated with responsiveness to
      tumour necrosis factor inhibitor (anti-TNF) treatment in rheumatoid arthritis
      (RA). The present study was undertaken to replicate these findings. In a
      retrospective case-case study including 1007 Danish anti-TNF-treated RA patients,
      we genotyped 7 previously reported associated single-nucleotide polymorphisms
      (SNPs) in these pathways. Furthermore, 5 SNPs previously reported by our group
      were genotyped in a subcohort (N=469). Primary analyses validated the IRAK3
      rs11541076 variant as associated (odds ratio (OR)=1.33, 95% confidence interval
      (CI): 1.00-1.77, P-value=0.047) with a positive treatment response (EULAR
      (European League Against Rheumatism) good/moderate vs none response at 4+/-2
      months), and found the NLRP3 rs461266 variant associated (OR=0.75, 95% CI: 0.60
      0.94, P=0.014) with a negative treatment response. Meta-analyses combining data
      from previous studies suggested smaller effect sizes of associations between
      variant alleles of CHUK rs11591741, NFKBIB rs3136645 and rs9403 and a negative
      treatment response. In conclusion, this study validates rs11541076 in IRAK3, a
      negative regulator of TLR signalling, as a predictor of anti-TNF treatment
      response, and suggests true positive associations of previously reported SNPs
      within genes encoding activators/inhibitors of NF-kappaB (CHUK, MYD88, NFKBIB,
      and NLRP3).

PMID- 27698402
TI  - Tamoxifen metabolism in breast cancer treatment: Taking the focus off the CYP2D6
      gene.

PMID- 27698403
TI  - A genetic variant in Rassf1a predicts outcome in mCRC patients treated with
      cetuximab plus chemotherapy: results from FIRE-3 and JACCRO 05 and 06 trials.
AB  - The Hippo pathway is involved in colorectal cancer (CRC) development and
      progression. The Hippo regulator Rassf1a is also involved in the Ras signaling
      cascade. In this work, we tested single nucleotide polymorphisms within Hippo
      components and their association with outcome in CRC patients treated with
      cetuximab. Two cohorts treated with cetuximab plus chemotherapy were evaluated
      (198 RAS wild-type (WT) patients treated with first-line FOLFIRI plus Cetuximab
      within the FIRE-3 trial and 67 Ras WT patients treated either with first-line
      mFOLFOX6 or SOX plus Cetuximab). In these two populations, Rassf1a rs2236947 was
      associated with overall survival (OS), as patients with a CC genotype had
      significantly longer OS compared with those with CA or AA genotypes. This
      association was stronger in patients with left-side CRC (hazard ratio (HR): 1.79
      (1.01-3.14); P=0.044 and HR: 2.83 (1.14-7.03); P=0.025, for Fire 3 and JACCRO
      cohorts, respectively). Rassf1a rs2236947 is a promising biomarker for patients
      treated with cetuximab plus chemotherapy.

PMID- 27698404
TI  - Neofunctionalization of zona pellucida proteins enhances freeze-prevention in the
      eggs of Antarctic notothenioids.
AB  - The mechanisms by which the eggs of the Antarctic notothenioid fishes avoid
      freezing are not fully understood. Zona pellucida proteins (ZPs) are constituents
      of the chorion which forms a protective matrix surrounding the egg. Here we
      report occurrence of freezing temperature-related gene expansion and acquisition
      of unusual ice melting-promoting (IMP) activity in a family of Antarctic
      notothenioid ZPs (AnnotoZPs). Members of AnnotoZPs are shown to bind with ice and
      non-colligatively depress the melting point of a solution in a range of 0.26 to
      0.65  degrees C at a moderate concentration. Eggs of zebrafishes expressing an
      AnnotoZP transgene show improved melting point depression and enhanced survival
      in freezing conditions. Mutational analyses in a representative AnnotoZP indicate
      the ZP domain and patches of acidic residues are essential structures for the IMP
      activity. AnnotoZPs, therefore, represent a group of macromolecules that prevent
      freezing by a unique ZP-ice interaction mechanism distinct from the known
      antifreeze proteins.

PMID- 27698405
TI  - Structural insights into the assembly and regulation of distinct viral capsid
      complexes.
AB  - The assembly and regulation of viral capsid proteins into highly ordered
      macromolecular complexes is essential for viral replication. Here, we utilize
      crystal structures of the capsid protein from the smallest and simplest known
      viruses capable of autonomously replicating in animal cells, circoviruses, to
      establish structural and mechanistic insights into capsid morphogenesis and
      regulation. The beak and feather disease virus, like many circoviruses, encode
      only two genes: a capsid protein and a replication initiation protein. The capsid
      protein forms distinct macromolecular assemblies during replication and here we
      elucidate these structures at high resolution, showing that these complexes
      reverse the exposure of the N-terminal arginine rich domain responsible for DNA
      binding and nuclear localization. We show that assembly of these complexes is
      regulated by single-stranded DNA (ssDNA), and provide a structural basis of
      capsid assembly around single-stranded DNA, highlighting novel binding interfaces
      distinct from the highly positively charged N-terminal ARM domain.

PMID- 27698407
TI  - Relationship between neuroticism, childhood trauma and cognitive-affective
      responses to auditory verbal hallucinations.
AB  - Neuroticism has been shown to adversely influence the development and outcome of
      psychosis. However, how this personality trait associates with the individual's
      responses to psychotic symptoms is less well known. Auditory verbal
      hallucinations (AVHs) have been reported by patients with psychosis and non
      clinical individuals. There is evidence that voice-hearers who are more
      distressed by and resistant against the voices, as well as those who appraise the
      voices as malevolent and powerful, have poorer outcome. This study aimed to
      examine the mechanistic association of neuroticism with the cognitive-affective
      reactions to AVH. We assessed 40 psychotic patients experiencing frequent AVHs,
      135 non-clinical participants experiencing frequent AVHs, and 126 healthy
      individuals. In both clinical and non-clinical voice-hearers alike, a higher
      level of neuroticism was associated with more distress and behavioral resistance
      in response to AVHs, as well as a stronger tendency to perceive voices as
      malevolent and powerful. Neuroticism fully mediated the found associations
      between childhood trauma and the individuals' cognitive-affective reactions to
      voices. Our results supported the role of neurotic personality in shaping
      maladaptive reactions to voices. Neuroticism may also serve as a putative
      mechanism linking childhood trauma and psychological reactions to voices.
      Implications for psychological models of hallucinations are discussed.

PMID- 27698406
TI  - Triggering signaling pathways using F-actin self-organization.
AB  - The spatiotemporal organization of proteins within cells is essential for cell
      fate behavior. Although it is known that the cytoskeleton is vital for numerous
      cellular functions, it remains unclear how cytoskeletal activity can shape and
      control signaling pathways in space and time throughout the cell cytoplasm. Here
      we show that F-actin self-organization can trigger signaling pathways by
      engineering two novel properties of the microfilament self-organization: (1) the
      confinement of signaling proteins and (2) their scaffolding along actin polymers.
      Using in vitro reconstitutions of cellular functions, we found that both the
      confinement of nanoparticle-based signaling platforms powered by F-actin
      contractility and the scaffolding of engineered signaling proteins along actin
      microfilaments can drive a signaling switch. Using Ran-dependent microtubule
      nucleation, we found that F-actin dynamics promotes the robust assembly of
      microtubules. Our in vitro assay is a first step towards the development of novel
      bottom-up strategies to decipher the interplay between cytoskeleton spatial
      organization and signaling pathway activity.

PMID- 27698408
TI  - Biodiversity of bacteriophages: morphological and biological properties of a
      large group of phages isolated from urban sewage.
AB  - A large scale analysis presented in this article focuses on biological and
      physiological variety of bacteriophages. A collection of 83 bacteriophages,
      isolated from urban sewage and able to propagate in cells of different bacterial
      hosts, has been obtained (60 infecting Escherichia coli, 10 infecting Pseudomonas
      aeruginosa, 4 infecting Salmonella enterica, 3 infecting Staphylococcus sciuri,
      and 6 infecting Enterococcus faecalis). High biological diversity of the
      collection is indicated by its characteristics, both morphological (electron
      microscopic analyses) and biological (host range, plaque size and morphology,
      growth at various temperatures, thermal inactivation, sensitivity to low and high
      pH, sensitivity to osmotic stress, survivability upon treatment with organic
      solvents and detergents), and further supported by hierarchical cluster analysis.
      By the end of the research no larger collection of phages from a single
      environmental source investigated by these means had been found. The finding was
      confirmed by whole genome analysis of 7 selected bacteriophages. Moreover,
      particular bacteriophages revealed unusual biological features, like the ability
      to form plaques at low temperature (4  degrees C), resist high temperature (62 
      degrees C or 95  degrees C) or survive in the presence of an organic solvents
      (ethanol, acetone, DMSO, chloroform) or detergent (SDS, CTAB, sarkosyl) making
      them potentially interesting in the context of biotechnological applications.

PMID- 27698410
TI  - Tuning Fullerene Intercalation in a Poly (thiophene) derivative by Controlling
      the Polymer Degree of Self-Organisation.
AB  - Controlling the nanoscale arrangement in polymer-fullerene organic solar cells is
      of paramount importance to boost the performance of such promising class of
      photovoltaic diodes. In this work, we use a pseudo-bilayer system made of
      poly(2,5-bis(3-hexadecylthiophen-2-yl)thieno[3,2-b]thiophene (PBTTT) and [6,6]
      phenyl-C61-butyric acid methyl ester (PCBM), to acquire a more complete
      understanding of the diffusion and intercalation of the fullerene-derivative
      within the polymer layer. By exploiting morphological and structural
      characterisation techniques, we observe that if we increase the film
      solidification time the polymer develops a higher crystalline order, and, as a
      result, it does not allow fullerene molecules to intercalate between the polymer
      side-chains. Gaining insight into the detailed fullerene intercalation mechanism
      is important for the development of organic photovoltaic diodes (PVDs).

PMID- 27698409
TI  - Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5
      N398 allele.
AB  - Genetic variation in nicotinic receptor alpha 5 (CHRNA5) has been associated with
      increased risk of addiction-associated phenotypes in humans yet little is known
      the underlying neural basis. Induced pluripotent stem cells (iPSCs) were derived
      from donors homozygous for either the major (D398) or the minor (N398) allele of
      the nonsynonymous single nucleotide polymorphism (SNP), rs16969968, in CHRNA5. To
      understand the impact of these nicotinic receptor variants in humans, we
      differentiated these iPSCs to dopamine (DA) or glutamatergic neurons and then
      tested their functional properties and response to nicotine. Results show that
      N398 variant human DA neurons differentially express genes associated with ligand
      receptor interaction and synaptic function. While both variants exhibited
      physiological properties consistent with mature neuronal function, the N398
      neuronal population responded more actively with an increased excitatory
      postsynaptic current response upon the application of nicotine in both DA and
      glutamatergic neurons. Glutamatergic N398 neurons responded to lower nicotine
      doses (0.1 MUM) with greater frequency and amplitude but they also exhibited
      rapid desensitization, consistent with previous analyses of N398-associated
      nicotinic receptor function. This study offers a proof-of-principle for utilizing
      human neurons to study gene variants contribution to addiction.

PMID- 27698411
TI  - An expression based REST signature predicts patient survival and therapeutic
      response for glioblastoma multiforme.
AB  - Proper regulation of neuronal gene expression is crucial for the development and
      differentiation of the central nervous system. The transcriptional repressor REST
      (repressor element-1 silencing transcription factor) is a key regulator in
      differentiation of pluripotent stem cells to neuronal progenitors and mature
      neurons. Dysregulated REST activity has been implicated in various diseases,
      among which the most deadly is glioblastoma multiforme (GBM). Here we have
      developed an expression-based REST signature (EXPREST), a device providing
      quantitative measurements of REST activity for GBM tumors. EXPREST robustly
      quantifies REST activity (REST score) using gene expression profiles in absence
      of clinic-pathologic assessments of REST. Molecular characterization of REST
      activity identified global alterations at the DNA, RNA, protein and microRNA
      levels, suggesting a widespread role of REST in GBM tumorigenesis. Although
      originally aimed to capture REST activity, REST score was found to be a
      prognostic factor for overall survival. Further, cell lines with enhanced REST
      activity was found to be more sensitive to IGF1R, VEGFR and ABL inhibitors. In
      contrast, cell lines with low REST score were more sensitive to cytotoxic drugs
      including Mitomycin, Camptothecin and Cisplatin. Together, our work suggests that
      therapeutic targeting of REST provides a promising opportunity for GBM treatment.

PMID- 27698412
TI  - ALB3 Insertase Mediates Cytochrome b6 Co-translational Import into the Thylakoid
      Membrane.
AB  - The cytochrome b6 f complex occupies an electrochemically central position in the
      electron-transport chain bridging the photosynthetic reaction center of PS I and
      PS II. In plants, the subunits of these thylakoid membrane protein complexes are
      both chloroplast and nuclear encoded. How the chloroplast-encoded subunits of
      multi-spanning cytochrome b6 are targeted and inserted into the thylakoid
      membrane is not fully understood. Experimental approaches to evaluate the
      cytochrome b6 import mechanism in vivo have been limited to bacterial membranes
      and were not a part of the chloroplast environment. To evaluate the mechanism
      governing cytochrome b6 integration in vivo, we performed a comparative analysis
      of both native and synthetic cytochrome b6 insertion into purified thylakoids.
      Using biophysical and biochemical methods, we show that cytochrome b6 insertion
      into the thylakoid membrane is a non-spontaneous co-translational process that
      involves ALB3 insertase. Furthermore, we provided evidence that CSP41
      (chloroplast stem-loop-binding protein of 41 kDa) interacts with RNC-cytochrome
      b6 complexes, and may be involved in cytochrome b6 (petB) transcript
      stabilization or processing.

PMID- 27698413
TI  - Lithium-ion-based solid electrolyte tuning of the carrier density in graphene.
AB  - We have developed a technique to tune the carrier density in graphene using a
      lithium-ion-based solid electrolyte. We demonstrate that the solid electrolyte
      can be used as both a substrate to support graphene and a back gate. It can
      induce a change in the carrier density as large as 1 * 1014 cm-2, which is much
      larger than that induced with oxide-film dielectrics, and it is comparable with
      that induced by liquid electrolytes. Gate modulation of the carrier density is
      still visible at 150 K, which is lower than the glass transition temperature of
      most liquid gating electrolytes.

PMID- 27698414
TI  - Scaffold Hopping Toward Agomelatine: Novel 3, 4-Dihydroisoquinoline Compounds as
      Potential Antidepressant Agents.
AB  - A scaffold-hopping strategy toward Agomelatine based on in silico screening and
      knowledge analysis was employed to design novel antidepressant agents. A series
      of 3, 4-dihydroisoquinoline compounds were selected for chemical synthesis and
      biological assessment. Three compounds (6a-1, 6a-2, 6a-9) demonstrated protective
      effects on corticosterone-induced lesion of PC12 cells. Compound 6a-1 also
      displayed low inhibitory effects on the growth of HEK293 and L02 normal cells and
      it was further evaluated for its potential antidepressant effects in vivo. The
      forced swim test (FST) results revealed that compound 6a-1 remarkably reduced the
      immobility time of rats and the open field test (OFT) results indicated a better
      general locomotor activity of the rats treated with compound 6a-1 than those with
      Agomelatine or Fluoxetine. Mechanism studies implied that compound 6a-1 can
      significantly reduce PC12 cell apoptosis by up-regulation of GSH and down
      regulation of ROS in corticosterone-induced lesion of PC12 cells. Meanwhile, the
      down-regulation of calcium ion concentration and up-regulation of BDNF level in
      PC12 cells may account for the neuroprotective effects. Furthermore, compound 6a
      1 can increase cell survival and cell proliferation, promote cell maturation in
      the rat hippocampus after chronic treatment. The acute toxicity data in vivo
      indicated compound 6a-1 exhibited less hepatotoxicity than Agomelatine.

PMID- 27698415
TI  - Real-space investigation of energy transfer in heterogeneous molecular dimers.
AB  - Given its central role in photosynthesis and artificial energy-harvesting
      devices, energy transfer has been widely studied using optical spectroscopy to
      monitor excitation dynamics and probe the molecular-level control of energy
      transfer between coupled molecules. However, the spatial resolution of
      conventional optical spectroscopy is limited to a few hundred nanometres and thus
      cannot reveal the nanoscale spatial features associated with such processes. In
      contrast, scanning tunnelling luminescence spectroscopy has revealed the energy
      dynamics associated with phenomena ranging from single-molecule
      electroluminescence, absorption of localized plasmons and quantum interference
      effects to energy delocalization and intervalley electron scattering with
      submolecular spatial resolution in real space. Here we apply this technique to
      individual molecular dimers that comprise a magnesium phthalocyanine and a free
      base phthalocyanine (MgPc and H2Pc) and find that locally exciting MgPc with the
      tunnelling current of the scanning tunnelling microscope generates a luminescence
      signal from a nearby H2Pc molecule as a result of resonance energy transfer from
      the former to the latter. A reciprocating resonance energy transfer is observed
      when exciting the second singlet state (S2) of H2Pc, which results in energy
      transfer to the first singlet state (S1) of MgPc and final funnelling to the S1
      state of H2Pc. We also show that tautomerization of H2Pc changes the energy
      transfer characteristics within the dimer system, which essentially makes H2Pc a
      single-molecule energy transfer valve device that manifests itself by blinking
      resonance energy transfer behaviour.

PMID- 27698416
TI  - Tissue-specific mutation accumulation in human adult stem cells during life.
AB  - The gradual accumulation of genetic mutations in human adult stem cells (ASCs)
      during life is associated with various age-related diseases, including cancer.
      Extreme variation in cancer risk across tissues was recently proposed to depend
      on the lifetime number of ASC divisions, owing to unavoidable random mutations
      that arise during DNA replication. However, the rates and patterns of mutations
      in normal ASCs remain unknown. Here we determine genome-wide mutation patterns in
      ASCs of the small intestine, colon and liver of human donors with ages ranging
      from 3 to 87 years by sequencing clonal organoid cultures derived from primary
      multipotent cells. Our results show that mutations accumulate steadily over time
      in all of the assessed tissue types, at a rate of approximately 40 novel
      mutations per year, despite the large variation in cancer incidence among these
      tissues. Liver ASCs, however, have different mutation spectra compared to those
      of the colon and small intestine. Mutational signature analysis reveals that this
      difference can be attributed to spontaneous deamination of methylated cytosine
      residues in the colon and small intestine, probably reflecting their high ASC
      division rate. In liver, a signature with an as-yet-unknown underlying mechanism
      is predominant. Mutation spectra of driver genes in cancer show high similarity
      to the tissue-specific ASC mutation spectra, suggesting that intrinsic mutational
      processes in ASCs can initiate tumorigenesis. Notably, the inter-individual
      variation in mutation rate and spectra are low, suggesting tissue-specific
      activity of common mutational processes throughout life.

PMID- 27698417
TI  - A cholinergic basal forebrain feeding circuit modulates appetite suppression.
AB  - Atypical food intake is a primary cause of obesity and other eating and metabolic
      disorders. Insight into the neural control of feeding has previously focused
      mainly on signalling mechanisms associated with the hypothalamus, the major
      centre in the brain that regulates body weight homeostasis. However, roles of non
      canonical central nervous system signalling mechanisms in regulating feeding
      behaviour have been largely uncharacterized. Acetylcholine has long been proposed
      to influence feeding owing in part to the functional similarity between
      acetylcholine and nicotine, a known appetite suppressant. Nicotine is an
      exogenous agonist for acetylcholine receptors, suggesting that endogenous
      cholinergic signalling may play a part in normal physiological regulation of
      feeding. However, it remains unclear how cholinergic neurons in the brain
      regulate food intake. Here we report that cholinergic neurons of the mouse basal
      forebrain potently influence food intake and body weight. Impairment of
      cholinergic signalling increases food intake and results in severe obesity,
      whereas enhanced cholinergic signalling decreases food consumption. We found that
      cholinergic circuits modulate appetite suppression on downstream targets in the
      hypothalamus. Together our data reveal the cholinergic basal forebrain as a major
      modulatory centre underlying feeding behaviour.

PMID- 27698420
TI  - Pore architecture of TRIC channels and insights into their gating mechanism.
AB  - Intracellular Ca2+ signalling processes are fundamental to muscle contraction,
      neurotransmitter release, cell growth and apoptosis. Release of Ca2+ from the
      intracellular stores is supported by a series of ion channels in sarcoplasmic or
      endoplasmic reticulum (SR/ER). Among them, two isoforms of the trimeric
      intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the
      release of Ca2+ through the ryanodine receptor or inositol triphosphate receptor,
      and maintain the homeostasis of ions within SR/ER lumen. Genetic ablations or
      mutations of TRIC channels are associated with hypertension, heart disease,
      respiratory defects and brittle bone disease. Despite the pivotal function of
      TRIC channels in Ca2+ signalling, their pore architectures and gating mechanisms
      remain unknown. Here we present the structures of TRIC-B1 and TRIC-B2 channels
      from Caenorhabditis elegans in complex with endogenous phosphatidylinositol-4,5
      biphosphate (PtdIns(4,5)P2, also known as PIP2) lipid molecules. The TRIC-B1/B2
      proteins and PIP2 assemble into a symmetrical homotrimeric complex. Each monomer
      contains an hourglass-shaped hydrophilic pore contained within a seven
      transmembrane-helix domain. Structural and functional analyses unravel the
      central role of PIP2 in stabilizing the cytoplasmic gate of the ion permeation
      pathway and reveal a marked Ca2+-induced conformational change in a cytoplasmic
      loop above the gate. A mechanistic model has been proposed to account for the
      complex gating mechanism of TRIC channels.

PMID- 27698419
TI  - X-ray structure of the human alpha4beta2 nicotinic receptor.
AB  - Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast
      chemical neurotransmission at the neuromuscular junction and have diverse
      signalling roles in the central nervous system. The nicotinic receptor has been a
      model system for cell-surface receptors, and specifically for ligand-gated ion
      channels, for well over a century. In addition to the receptors' prominent roles
      in the development of the fields of pharmacology and neurobiology, nicotinic
      receptors are important therapeutic targets for neuromuscular disease, addiction,
      epilepsy and for neuromuscular blocking agents used during surgery. The overall
      architecture of the receptor was described in landmark studies of the nicotinic
      receptor isolated from the electric organ of Torpedo marmorata. Structures of a
      soluble ligand-binding domain have provided atomic-scale insights into receptor
      ligand interactions, while high-resolution structures of other members of the
      pentameric receptor superfamily provide touchstones for an emerging allosteric
      gating mechanism. All available high-resolution structures are of homopentameric
      receptors. However, the vast majority of pentameric receptors (called Cys-loop
      receptors in eukaryotes) present physiologically are heteromeric. Here we present
      the X-ray crystallographic structure of the human alpha4beta2 nicotinic receptor,
      the most abundant nicotinic subtype in the brain. This structure provides
      insights into the architectural principles governing ligand recognition,
      heteromer assembly, ion permeation and desensitization in this prototypical
      receptor class.

PMID- 27698418
TI  - Genomic insights into the peopling of the Southwest Pacific.
AB  - The appearance of people associated with the Lapita culture in the South Pacific
      around 3,000 years ago marked the beginning of the last major human dispersal to
      unpopulated lands. However, the relationship of these pioneers to the long
      established Papuan people of the New Guinea region is unclear. Here we present
      genome-wide ancient DNA data from three individuals from Vanuatu (about 3,100
      2,700 years before present) and one from Tonga (about 2,700-2,300 years before
      present), and analyse them with data from 778 present-day East Asians and
      Oceanians. Today, indigenous people of the South Pacific harbour a mixture of
      ancestry from Papuans and a population of East Asian origin that no longer exists
      in unmixed form, but is a match to the ancient individuals. Most analyses have
      interpreted the minimum of twenty-five per cent Papuan ancestry in the region
      today as evidence that the first humans to reach Remote Oceania, including
      Polynesia, were derived from population mixtures near New Guinea, before their
      further expansion into Remote Oceania. However, our finding that the ancient
      individuals had little to no Papuan ancestry implies that later human population
      movements spread Papuan ancestry through the South Pacific after the first
      peopling of the islands.

PMID- 27698422
TI  - Cascaded plasmon-plasmon coupling mediated energy transfer across stratified
      metal-dielectric nanostructures.
AB  - Surface plasmon (SP) coupling has been successfully applied to nonradiative
      energy transfer via exciton-plasmon-exciton coupling in conventionally sandwiched
      donor-metal film-acceptor configurations. However, these structures lack the
      desired efficiency and suffer poor photoemission due to the high energy loss.
      Here, we show that the cascaded exciton-plasmon-plasmon-exciton coupling in
      stratified architecture enables an efficient energy transfer mechanism. The
      overlaps of the surface plasmon modes at the metal-dielectric and dielectric
      metal interfaces allow for strong cross-coupling in comparison with the single
      metal film configuration. The proposed architecture has been demonstrated through
      the analytical modeling and numerical simulation of an oscillating dipole near
      the stratified nanostructure of metal-dielectric-metal-acceptor. Consistent with
      theoretical and numerical results, experimental measurements confirm at least 50%
      plasmon resonance energy transfer enhancement in the donor-metal-dielectric-metal
      acceptor compared to the donor-metal-acceptor structure. Cascaded plasmon-plasmon
      coupling enables record high efficiency for exciton transfer through metallic
      structures.

PMID- 27698421
TI  - Effect of an Experimental Direct Pulp-capping Material on the Properties and
      Osteogenic Differentiation of Human Dental Pulp Stem Cells.
AB  - Effective pulp-capping materials must have antibacterial properties and induce
      dentin bridge formation; however, many current materials do not satisfy clinical
      requirements. Accordingly, the effects of an experiment pulp-capping material
      (Exp) composed of an antibacterial resin monomer (MAE-DB) and Portland cement
      (PC) on the viability, adhesion, migration, and differentiation of human dental
      pulp stem cells (hDPSCs) were examined. Based on a Cell Counting Kit-8 assay,
      hDPSCs exposed to Exp extracts showed limited viability at 24 and 48 h, but
      displayed comparable viability to the control at 72 h. hDPSC treatment with Exp
      extracts enhanced cellular adhesion and migration according to in vitro scratch
      wound healing and Transwell migration assays. Exp significantly upregulated the
      expression of osteogenesis-related genes. The hDPSCs cultured with Exp exhibited
      higher ALP activity and calcium deposition in vitro compared with the control
      group. The novel material showed comparable cytocompatibility to control cells
      and promoted the adhesion, migration, and osteogenic differentiation of hDPSCs,
      indicating excellent biocompatibility. This new direct pulp-capping material
      containing MAE-DB and PC shows promise as a potential alternative to conventional
      materials for direct pulp capping.

PMID- 27698424
TI  - Structure of the Neisseria meningitidis Type IV pilus.
AB  - Neisseria meningitidis use Type IV pili (T4P) to adhere to endothelial cells and
      breach the blood brain barrier, causing cause fatal meningitis. T4P are
      multifunctional polymers of the major pilin protein, which share a conserved
      hydrophobic N terminus that is a curved extended alpha-helix, alpha1, in X-ray
      crystal structures. Here we report a 1.44 A crystal structure of the N.
      meningitidis major pilin PilE and a ~6 A cryo-electron microscopy reconstruction
      of the intact pilus, from which we built an atomic model for the filament. This
      structure reveals the molecular arrangement of the N-terminal alpha-helices in
      the filament core, including a melted central portion of alpha1 and a bridge of
      electron density consistent with a predicted salt bridge necessary for pilus
      assembly. This structure has important implications for understanding pilus
      biology.

PMID- 27698423
TI  - Deubiquitinase activity is required for the proteasomal degradation of misfolded
      cytosolic proteins upon heat-stress.
AB  - Elimination of misfolded proteins is crucial for proteostasis and to prevent
      proteinopathies. Nedd4/Rsp5 emerged as a major E3-ligase involved in multiple
      quality control pathways that target misfolded plasma membrane proteins,
      aggregated polypeptides and cytosolic heat-induced misfolded proteins for
      degradation. It remained unclear how in one case cytosolic heat-induced Rsp5
      substrates are destined for proteasomal degradation, whereas other Rsp5 quality
      control substrates are otherwise directed to lysosomal degradation. Here we find
      that Ubp2 and Ubp3 deubiquitinases are required for the proteasomal degradation
      of cytosolic misfolded proteins targeted by Rsp5 after heat-shock (HS). The two
      deubiquitinases associate more with Rsp5 upon heat-stress to prevent the assembly
      of K63-linked ubiquitin on Rsp5 heat-induced substrates. This activity was
      required to promote the K48-mediated proteasomal degradation of Rsp5 HS-induced
      substrates. Our results indicate that ubiquitin chain editing is key to the
      cytosolic protein quality control under stress conditions.

PMID- 27698426
TI  - Magnetodielectric detection of magnetic quadrupole order in Ba(TiO)Cu4(PO4)4 with
      Cu4O12 square cupolas.
AB  - In vortex-like spin arrangements, multiple spins can combine into emergent
      multipole moments. Such multipole moments have broken space-inversion and time
      reversal symmetries, and can therefore exhibit linear magnetoelectric (ME)
      activity. Three types of such multipole moments are known: toroidal; monopole;
      and quadrupole moments. So far, however, the ME activity of these multipole
      moments has only been established experimentally for the toroidal moment. Here we
      propose a magnetic square cupola cluster, in which four corner-sharing square
      coordinated metal-ligand fragments form a noncoplanar buckled structure, as a
      promising structural unit that carries an ME-active multipole moment. We
      substantiate this idea by observing clear magnetodielectric signals associated
      with an antiferroic ME-active magnetic quadrupole order in the real material
      Ba(TiO)Cu4(PO4)4. The present result serves as a useful guide for exploring and
      designing new ME-active materials based on vortex-like spin arrangements.

PMID- 27698425
TI  - Novel near-infrared emission from crystal defects in MoS2 multilayer flakes.
AB  - The structural defects in two-dimensional transition metal dichalcogenides,
      including point defects, dislocations and grain boundaries, are scarcely
      considered regarding their potential to manipulate the electrical and optical
      properties of this class of materials, notwithstanding the significant advances
      already made. Indeed, impurities and vacancies may influence the exciton
      population, create disorder-induced localization, as well as modify the
      electrical behaviour of the material. Here we report on the experimental
      evidence, confirmed by ab initio calculations, that sulfur vacancies give rise to
      a novel near-infrared emission peak around 0.75 eV in exfoliated MoS2 flakes. In
      addition, we demonstrate an excess of sulfur vacancies at the flake's edges by
      means of cathodoluminescence mapping, aberration-corrected transmission electron
      microscopy imaging and electron energy loss analyses. Moreover, we show that
      ripplocations, extended line defects peculiar to this material, broaden and
      redshift the MoS2 indirect bandgap emission.

PMID- 27698427
TI  - Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine
      fear responsiveness to unpredictable threat.
AB  - The brain circuits underlying behavioral fear have been extensively studied over
      the last decades. Although the vast majority of experimental studies assess fear
      as a transient state of apprehension in response to a discrete threat, such
      phasic states of fear can shift to a sustained anxious apprehension, particularly
      in face of diffuse cues with unpredictable environmental contingencies.
      Unpredictability, in turn, is considered an important variable contributing to
      anxiety disorders. The networks of the extended amygdala have been suggested keys
      to the control of phasic and sustained states of fear, although the underlying
      synaptic pathways and mechanisms remain poorly understood. Here, we show that the
      endocannabinoid system acting in synaptic circuits of the extended amygdala can
      explain the fear response profile during exposure to unpredictable threat. Using
      fear training with predictable or unpredictable cues in mice, combined with local
      and cell-type-specific deficiency and rescue of cannabinoid type 1 (CB1)
      receptors, we found that presynaptic CB1 receptors on distinct amygdala
      projections to bed nucleus of the stria terminalis (BNST) are both necessary and
      sufficient for the shift from phasic to sustained fear in response to an
      unpredictable threat. These results thereby identify the causal role of a defined
      protein in a distinct brain pathway for the temporal development of a sustained
      state of anxious apprehension during unpredictability of environmental
      influences, reminiscent of anxiety symptoms in humans.

PMID- 27698428
TI  - Predicting the functional states of human iPSC-derived neurons with single-cell
      RNA-seq and electrophysiology.
AB  - Human neural progenitors derived from pluripotent stem cells develop into
      electrophysiologically active neurons at heterogeneous rates, which can confound
      disease-relevant discoveries in neurology and psychiatry. By combining patch
      clamping, morphological and transcriptome analysis on single-human neurons in
      vitro, we defined a continuum of poor to highly functional electrophysiological
      states of differentiated neurons. The strong correlations between action
      potentials, synaptic activity, dendritic complexity and gene expression highlight
      the importance of methods for isolating functionally comparable neurons for in
      vitro investigations of brain disorders. Although whole-cell electrophysiology is
      the gold standard for functional evaluation, it often lacks the scalability
      required for disease modeling studies. Here, we demonstrate a multimodal machine
      learning strategy to identify new molecular features that predict the
      physiological states of single neurons, independently of the time spent in vitro.
      As further proof of concept, we selected one of the potential neurophysiological
      biomarkers identified in this study-GDAP1L1-to isolate highly functional live
      human neurons in vitro.

PMID- 27698429
TI  - Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD
      like phenotype in mice.
AB  - Autism spectrum disorder (ASD) occurs in 1 in 68 births, preferentially affecting
      males. It encompasses a group of neurodevelopmental abnormalities characterized
      by impaired social interaction and communication, stereotypic behaviors and motor
      dysfunction. Although recent advances implicate maternal brain-reactive
      antibodies in a causative role in ASD, a definitive assessment of their
      pathogenic potential requires cloning of such antibodies. Here, we describe the
      isolation and characterization of monoclonal brain-reactive antibodies from blood
      of women with brain-reactive serology and a child with ASD. We further
      demonstrate that male but not female mice exposed in utero to the C6 monoclonal
      antibody, binding to contactin-associated protein-like 2 (Caspr2), display
      abnormal cortical development, decreased dendritic complexity of excitatory
      neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as
      impairments in sociability, flexible learning and repetitive behavior. Anti
      Caspr2 antibodies are frequent in women with brain-reactive serology and a child
      with ASD. Together these studies provide a methodology for obtaining monclonal
      brain-reactive antibodies from blood B cells, demonstrate that ASD can result
      from in utero exposure to maternal brain-reactive antibodies of single
      specificity and point toward the exciting possibility of prognostic and
      protective strategies.

PMID- 27698431
TI  - Insulin resistance-a missing link no more.

PMID- 27698430
TI  - Hippocampal bone morphogenetic protein signaling mediates behavioral effects of
      antidepressant treatment.
AB  - Many antidepressants stimulate adult hippocampal neurogenesis, but the mechanisms
      by which they increase neurogenesis and modulate behavior are incompletely
      understood. Here we show that hippocampal bone morphogenetic protein (BMP)
      signaling is modulated by antidepressant treatment, and that the changes in BMP
      signaling mediate effects of antidepressant treatment on neural progenitor cell
      proliferation and behavior. Treatment with the selective serotonin reuptake
      inhibitor fluoxetine suppressed BMP signaling in the adult mouse hippocampus both
      by decreasing levels of BMP4 ligand and increasing production of the BMP
      inhibitor noggin. Increasing BMP signaling in the hippocampus via viral
      overexpression of BMP4 blocked the effects of fluoxetine on proliferation in the
      dentate gyrus and on depressive behavior. Conversely, inhibiting BMP signaling
      via viral overexpression of noggin in the hippocampus or infusion of noggin into
      the ventricles exerted antidepressant and anxiolytic activity along with an
      increase in hippocampal neurogenesis. Similarly, conditional genetic deletion of
      the type II BMP receptor in Ascl1-expressing cells promoted neurogenesis and
      reduced anxiety- and depression-like behaviors, suggesting that neural progenitor
      cells contribute to the effects of BMP signaling on affective behavior. These
      observations indicate that BMP signaling in the hippocampus regulates depressive
      behavior, and that decreasing BMP signaling may be required for the effects of
      some antidepressants. Thus BMP signaling is a new and powerful potential target
      for the treatment of depression.

PMID- 27698432
TI  - Non-genetic transgenerational transmission of bipolar disorder: targeting DNA
      methyltransferases.

PMID- 27698433
TI  - Acute stress is not acute: sustained enhancement of glutamate release after acute
      stress involves readily releasable pool size and synapsin I activation.

PMID- 27698434
TI  - In vivo imaging of brain microglial activity in antipsychotic-free and medicated
      schizophrenia: a [11C](R)-PK11195 positron emission tomography study.
AB  - Positron emission tomography (PET) imaging of the 18 kDa translocator protein
      (TSPO) has been used to investigate whether microglial activation, an indication
      of neuroinflammation, is evident in the brain of adults with schizophrenia.
      Interpretation of these studies is confounded by potential modulatory effects of
      antipsychotic medication on microglial activity. In the first such study in
      antipsychotic-free schizophrenia, we have used [11C](R)-PK11195 PET to compare
      TSPO availability in a predominantly antipsychotic-naive group of moderate-to
      severely symptomatic unmedicated patients (n=8), similarly symptomatic medicated
      patients with schizophrenia taking risperidone or paliperidone by regular
      intramuscular injection (n=8), and healthy comparison subjects (n=16). We found
      no evidence for increased TSPO availability in antipsychotic-free patients
      compared with healthy controls (mean difference 4%, P=0.981). However, TSPO
      availability was significantly elevated in medicated patients (mean increase 88%,
      P=0.032) across prefrontal (dorsolateral, ventrolateral, orbital), anterior
      cingulate and parietal cortical regions. In the patients, TSPO availability was
      also strongly correlated with negative symptoms measured using the Positive and
      Negative Syndrome Scale across all the brain regions investigated (r=0.651
      0.741). We conclude that the pathophysiology of schizophrenia is not associated
      with microglial activation in the 2-6 year period following diagnosis. The
      elevation in the medicated patients may be a direct effect of the antipsychotic,
      although this study cannot exclude treatment resistance and/or longer illness
      duration as potential explanations. It also remains to be determined whether it
      is present only in a subset of patients, represents a pro- or anti-inflammatory
      state, its association with primary negative symptoms, and whether there are
      significant differences between antipsychotics.

PMID- 27698436
TI  - Entrainment of circadian rhythms to irregular light/dark cycles: a subterranean
      perspective.
AB  - Synchronization of biological rhythms to the 24-hour day/night has long been
      studied with model organisms, under artificial light/dark cycles in the
      laboratory. The commonly used rectangular light/dark cycles, comprising hours of
      continuous light and darkness, may not be representative of the natural light
      exposure for most species, including humans. Subterranean rodents live in dark
      underground tunnels and offer a unique opportunity to investigate extreme
      mechanisms of photic entrainment in the wild. Here, we show automated field
      recordings of the daily light exposure patterns in a South American subterranean
      rodent, the tuco-tuco (Ctenomys aff. knighti ). In the laboratory, we exposed
      tuco-tucos to a simplified version of this natural light exposure pattern, to
      determine the minimum light timing information that is necessary for
      synchronization. As predicted from our previous studies using mathematical
      modeling, the activity rhythm of tuco-tucos synchronized to this mostly
      simplified light/dark regimen consisting of a single light pulse per day,
      occurring at randomly scattered times within a day length interval. Our
      integrated semi-natural, lab and computer simulation findings indicate that
      photic entrainment of circadian oscillators is robust, even in face of
      artificially reduced exposure and increased phase instability of the
      synchronizing stimuli.

PMID- 27698437
TI  - Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode
      of action of glycoengineered anti-CD20 antibodies.
AB  - Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a
      number of B cell malignancies and autoimmune disorders. Glycoengineering of anti
      CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody
      dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in
      vitro studies. However, where and how glycoengineered Ab may potentiate
      therapeutic responses in vivo is yet to be elucidated. Here, we have performed
      mouse liver transplants to demonstrate that the liver is sufficient to mediate
      systemic B cells depletion after anti-CD20 treatment. Relying on intravital two
      photon imaging of human CD20-expressing mice, we provide evidence that ADP by
      Kupffer cells (KC) is a major mechanism for rituximab-mediated B cell depletion.
      Notably, a glycoengineered anti-mouse CD20 Ab but not its wild-type counterpart
      triggered potent KC-mediated B cell depletion at low doses. Finally, distinct
      thresholds for KC phagocytosis were also observed for GA101 (obinutuzumab), a
      humanized glycoengineered type II anti-CD20 Ab and rituximab. Thus, we propose
      that enhanced phagocytosis of circulating B cells by KC represents an important
      in vivo mechanism underlying the improved activity of glycoengineered anti-CD20
      mAbs.

PMID- 27698435
TI  - Sex pheromone recognition and characterization of three pheromone-binding
      proteins in the legume pod borer, Maruca vitrata Fabricius (Lepidoptera:
      Crambidae).
AB  - Pheromone-binding proteins (PBPs) are essential for the filtering, binding and
      transporting of sex pheromones across sensillum lymph to membrane-associated
      pheromone receptors of moths. In this study, three novel PBP genes were expressed
      in Escherichia coli to examine their involvement in the sex pheromone perception
      of Maruca vitrata. Fluorescence binding experiments indicated that MvitPBP1-3 had
      strong binding affinities with four sex pheromones. Moreover, molecular docking
      results demonstrated that six amino acid residues of three MvitPBPs were involved
      in the binding of the sex pheromones. These results suggested that MvitPBP1-3
      might play critical roles in the perception of female sex pheromones.
      Additionally, the binding capacity of MvitPBP3 with the host-plant floral
      volatiles was high and was similar to that of MvitGOBP2. Furthermore, sequence
      alignment and docking analysis showed that both MvitGOBP2 and MvitPBP3 possessed
      an identical key binding site (arginine, R130/R140) and a similar protein pocket
      structure around the binding cavity. Therefore, we hypothesized that MvitPBP3 and
      MvitGOBP2 might have synergistic roles in binding different volatile ligands. In
      combination, the use of synthetic sex pheromones and floral volatiles from host
      plant may be used in the exploration for more efficient monitoring and integrated
      management strategies for the legume pod borer in the field.

PMID- 27698438
TI  - Nuclear DNA content in Miscanthus sp. and the geographical variation pattern in
      Miscanthus lutarioriparius.
AB  - The genome sizes of five Miscanthus species, including 79 accessions of M.
      lutarioriparius, 8 of M. floridulus, 6 of M. sacchariflorus, 7 of M. sinensis,
      and 4 of M. * giganteus were examined using flow cytometry. The overall average
      nuclear DNA content were 4.256 +/- 0.6 pg/2C in M. lutarioriparius, 5.175 +/- 0.3
      pg/2C in M. floridulus, 3.956 +/- 0.2 pg/2C in M. sacchariflorus, 5.272 +/- 0.2
      pg/2C in M. sinensis, and 6.932 +/- 0.1 pg/2C in M. * giganteus. Interspecific
      variation was found at the diploid level, suggesting that DNA content might be a
      parameter that can be used to differentiate the species. Tetraploid populations
      were found in M. lutarioriparius, M. sacchariflorus, and M. sinensis, and their
      DNA content were 8.34 +/- 1.2, 8.52, and 8.355 pg, respectively. The association
      between the DNA content of M. lutarioriparius, collected from representative
      ranges across the Yangtze River, and its geographic distribution was
      statistically analyzed. A consistent pattern of DNA content variation in 79 M.
      lutarioriparius accessions across its entire geographic range was found in this
      study. Along the Yangtze River, the DNA content of M. lutarioriparius tended to
      increase from the upstream to the downstream areas, and almost all tetraploids
      gathered in the upstream area extended to coastal regions.

PMID- 27698439
TI  - Obesity and prostate cancer-specific mortality after radical prostatectomy:
      results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.
AB  - BACKGROUND: At the population level, obesity is associated with prostate cancer
      (PC) mortality. However, few studies analyzed the associations between obesity
      and long-term PC-specific outcomes after initial treatment. METHODS: We conducted
      a retrospective analysis of 4268 radical prostatectomy patients within the Shared
      Equal Access Regional Cancer Hospital (SEARCH) database. Cox models accounting
      for known risk factors were used to examine the associations between body mass
      index (BMI) and PC-specific mortality (PCSM; primary outcome). Secondary outcomes
      included biochemical recurrence (BCR) and castration-resistant PC (CRPC). BMI was
      used as a continuous and categorical variable (normal <25 kg/m2, overweight 25
      29.9 kg/m2 and obese ?30 kg/m2). Median follow-up among all men who were alive at
      last follow-up was 6.8 years (interquartile range=3.5-11.0). During this time,
      1384 men developed BCR, 117 developed CRPC and 84 died from PC. Hazard ratios
      were analyzed using competing-risks regression analysis accounting for non-PC
      death as a competing risk. RESULTS: On crude analysis, higher BMI was not
      associated with risk of PCSM (P=0.112), BCR (0.259) and CRPC (P=0.277). However,
      when BMI was categorized, overweight (hazard ratio (HR) 1.99, P=0.034) and
      obesity (HR 1.97, P=0.048) were significantly associated with PCSM. Obesity and
      overweight were not associated with BCR or CRPC (all P?0.189). On multivariable
      analysis adjusting for both clinical and pathological features, results were
      little changed in that obesity (HR=2.05, P=0.039) and overweight (HR=1.88,
      P=0.061) were associated with higher risk of PCSM, but not with BCR or CRPC (all
      P?0.114) with the exception that the association for overweight was no longer
      statistical significant. CONCLUSIONS: Overweight and obesity were associated with
      increased risk of PCSM after radical prostatectomy. If validated in larger
      studies with longer follow-up, obesity may be established as a potentially
      modifiable risk factor for PCSM.

PMID- 27698440
TI  - Long-term oncological outcomes of apical positive surgical margins at radical
      prostatectomy in the Shared Equal Access Regional Cancer Hospital cohort.
AB  - BACKGROUND: Approximately 29-38% of all positive surgical margins (PSMs) at
      radical prostatectomy (RP) involve the apex. The prognostic significance of
      apical PSM remains unclear. We therefore compared the long-term oncologic
      outcomes of men with apical PSMs to those with negative PSMs, apical and other
      PSMs, and other PSMs at RP. METHODS: The SEARCH (Shared Equal Access Regional
      Cancer Hospital) database was used to identify 4031 men with prostate cancer
      (PCa) managed with RP with complete pathologic grade and stage data. Margin
      status was categorized as negative, apex only, or other positive. Multivariable
      Cox regression models adjusted for pathologic stage and grade were developed to
      test the relationship between margin status and biochemical recurrence (BCR),
      metastases and PCa death. RESULTS: In the final cohort, 34.3% had PSMs, whereas
      65.7% had negative margins. Univariable analysis showed that compared with
      negative margins, apex-only PSM was associated with BCR (hazard ratio (HR): 1.4
      [1.1-1.8]), but not metastases or PCa death, whereas apex and other PSMs were
      associated with BCR (HR: 3.3 [2.8-4]) and metastases (HR: 1.8 [1.02-3.1]) but not
      PCa death. Nonapical PSMs were associated with BCR (HR: 2.7 [2.4-3.1]),
      metastases (1.7 [1.2-2.5)] and PCa death (1.8 [1.05-3]). On multivariable
      analysis, apex-only, apex and other, and nonapical PSMs were associated with BCR
      but margin status was not associated with metastases or PCa death. CONCLUSIONS:
      In a large cohort of men undergoing RP, those with PSMs at the prostatic apex had
      lower BCR, metastases, or PCa death compared with those with PSMs at other
      locations. When adjusted for pathologic stage and grade, however, PSMs were
      associated with BCR but not long-term oncologic outcomes. These data confirm that
      men with apex-only PSMs may not be ideal candidates for adjuvant therapy after
      RP.

PMID- 27698441
TI  - Formal nomenclature and description of cryptic species of the Encyrtus sasakii
      complex (Hymenoptera: Encyrtidae).
AB  - With the recent development of molecular approaches to species delimitation, a
      growing number of cryptic species have been discovered in what had previously
      been thought to be single morpho-species. Molecular methods, such as DNA
      barcoding, have greatly enhanced our knowledge of taxonomy, but taxonomy remains
      incomplete and needs a formal species nomenclature and description to facilitate
      its use in other scientific fields. A previous study using DNA barcoding,
      geometric morphometrics and mating tests revealed at least two cryptic species in
      the Encyrtus sasakii complex. (Hymenoptera: Encyrtidae). To describe these two
      new species formally (Encyrtus eulecaniumiae sp. nov. and Encyrtus rhodococcusiae
      sp. nov.), a detailed morphometric study of Encyrtus spp. was performed in
      addition to the molecular analysis and evaluation of biological data.
      Morphometric analyses, a multivariate ratio analysis (MRA) and a geometric
      morphometric analysis (GMA) revealed a great number of differences between the
      species, but reliable characteristics were not observed for diagnosing the
      cryptic species. We thus diagnosed these three Encyrtus species on the basis of
      the characteristics that resulted from genetic markers (mitochondrial cytochrome
      c oxidase subunit I and nuclear 28S rRNA) and biological data. A formal
      nomenclature and description of cryptic species was provided on the basis of an
      integrated taxonomy.

PMID- 27698443
TI  - Microwave birefringent metamaterials for polarization conversion based on spoof
      surface plasmon polariton modes.
AB  - We propose the design of wideband birefringent metamaterials based on spoof
      surface plasmon polaritons (SSPPs). Spatial k-dispersion design of SSPP modes in
      metamaterials is adopted to achieve high-efficiency transmission of
      electromagnetic waves through the metamaterial layer. By anisotropic design, the
      transmission phase accumulation in metamaterials can be independently modulated
      for x- and y-polarized components of incident waves. Since the dispersion curve
      of SSPPs is nonlinear, frequency-dependent phase differences can be obtained
      between the two orthogonal components of transmitted waves. As an example, we
      demonstrate a microwave birefringent metamaterials composed of fishbone
      structures. The full-polarization-state conversions on the zero-longitude line of
      Poincare sphere can be fulfilled twice in 6-20 GHz for both linearly polarized
      (LP) and circularly polarized (CP) waves incidence. Besides, at a given
      frequency, the full-polarization-state conversion can be achieved by changing the
      polarization angle of the incident LP waves. Both the simulation and experiment
      results verify the high-efficiency polarization conversion functions of the
      birefringent metamaterial, including circular-to-circular, circular-to
      linear(linear-to-circular), linear-to-linear polarization conversions.

PMID- 27698442
TI  - Up-regulation of miR-95-3p in hepatocellular carcinoma promotes tumorigenesis by
      targeting p21 expression.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant cancers. To
      elucidate new regulatory mechanisms for heptocarcinogenesis, we investigated the
      regulation of p21, a cyclin-dependent kinase (CDK) inhibitor encoded by CDKN1A,
      in HCC. The expression level of p21 is decreased with the progression of HCC.
      Luciferase assays with a luciferase-p21-3' UTR reporter and its serial deletions
      identified a 15-bp repressor element at the 3'-UTR of CDKN1A, which contains a
      binding site for miR-95-3p. Mutation of the binding site eliminated the
      regulatory effect of miR-95-3p on p21 expression. Posttranscriptional regulation
      of p21 expression by miR-95-3p is mainly on the protein level (suppression of
      translation). Overexpression of miR-95-3p in two different HCC cell lines, HepG2
      and SMMC7721, significantly promoted cell proliferation, cell cycle progression
      and cell migration, whereas a miR-95-3p specific inhibitor decreased cell
      proliferation, cell cycle progression and cell migration. The effects of miR-95
      3p on cellular functions were rescued by overexpression of p21. Overexpression of
      miR-95-3p promoted cell proliferation and tumor growth in HCC xenograft mouse
      models. Expression of miR-95-3p was significantly higher in HCC samples than in
      adjacent non-cancerous samples. These results demonstrate that miR-95-3p is a
      potential new marker for HCC and regulates hepatocarcinogenesis by directly
      targeting CDKN1A/p21 expression.

PMID- 27698445
TI  - CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the
      CNS.

PMID- 27698444
TI  - Structure and specificity of the Type VI secretion system ClpV-TssC interaction
      in enteroaggregative Escherichia coli.
AB  - The Type VI secretion system (T6SS) is a versatile machine that delivers toxins
      into either eukaryotic or bacterial cells. It thus represents a key player in
      bacterial pathogenesis and inter-bacterial competition. Schematically, the T6SS
      can be viewed as a contractile tail structure anchored to the cell envelope. The
      contraction of the tail sheath propels the inner tube loaded with effectors
      towards the target cell. The components of the contracted tail sheath are then
      recycled by the ClpV AAA+ ATPase for a new cycle of tail elongation. The T6SS is
      widespread in Gram-negative bacteria and most of their genomes carry several
      copies of T6SS gene clusters, which might be activated in different conditions.
      Here, we show that the ClpV ATPases encoded within the two T6SS gene clusters of
      enteroaggregative Escherichia coli are not interchangeable and specifically
      participate to the activity of their cognate T6SS. Here we show that this
      specificity is dictated by interaction between the ClpV N-terminal domains and
      the N-terminal helices of their cognate TssC1 proteins. We also present the
      crystal structure of the ClpV1 N-terminal domain, alone or in complex with the
      TssC1 N-terminal peptide, highlighting the commonalities and diversities in the
      recruitment of ClpV to contracted sheaths.

PMID- 27698447
TI  - Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic
      leukemia in children.
AB  - In the treatment of childhood acute lymphoblastic leukemia (ALL), excess
      shortening of maintenance therapy resulted in high relapse rate, as shown by our
      previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1
      year from initiation of treatment. In this study, we aimed to confirm the long
      term outcome of L92-13, and to identify who can or cannot be cured by shorter
      duration of maintenance therapy. To obtain sentinel cytogenetics information that
      had been missed before, we performed genetic analysis with genomic microarray and
      target intron-capture sequencing from diagnostic bone marrow smear. Disease-free
      survival (DFS) at 10 years from the end of therapy was 66.0+/-2.8%. Females
      (n=138) had better DFS (74.6+/-3.7%) than males (n=142, 57.5+/-4.2%, P=0.002).
      Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9+/
      8.7% and 93.8+/-6.1%, respectively), whereas high hyperdiploidy (n=23) was the
      most unfavorable subgroup, with 56.6+/-10.3% of DFS. Short duration of therapy
      can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6
      RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on
      the impact of brief therapy.

PMID- 27698446
TI  - Expansion of Th1-like Vgamma9Vdelta2T cells by new-generation IMiDs, lenalidomide
      and pomalidomide, in combination with zoledronic acid.

PMID- 27698448
TI  - CO2 Capture in the Sustainable Wheat-Derived Activated Microporous Carbon
      Compartments.
AB  - Microporous carbon compartments (MCCs) were developed via controlled
      carbonization of wheat flour producing large cavities that allow CO2 gas
      molecules to access micropores and adsorb effectively. KOH activation of MCCs was
      conducted at 700  degrees C with varying mass ratios of KOH/C ranging from 1 to
      5, and the effects of activation conditions on the prepared carbon materials in
      terms of the characteristics and behavior of CO2 adsorption were investigated.
      Textural properties, such as specific surface area and total pore volume,
      linearly increased with the KOH/C ratio, attributed to the development of pores
      and enlargement of pores within carbon. The highest CO2 adsorption capacities of
      5.70 mol kg-1 at 0  degrees C and 3.48 mol kg-1 at 25  degrees C were obtained
      for MCC activated with a KOH/C ratio of 3 (MCC-K3). In addition, CO2 adsorption
      uptake was significantly dependent on the volume of narrow micropores with a pore
      size of less than 0.8 nm rather than the volume of larger pores or surface area.
      MCC-K3 also exhibited excellent cyclic stability, facile regeneration, and rapid
      adsorption kinetics. As compared to the pseudo-first-order model, the pseudo
      second-order kinetic model described the experimental adsorption data
      methodically.

PMID- 27698449
TI  - Cr(VI) induces premature senescence through ROS-mediated p53 pathway in L-02
      hepatocytes.
AB  - Hexavalent Chromium [Cr(VI)], which can be found of various uses in industries
      such as metallurgy and textile dying, can cause a number of human disease
      including inflammation and cancer. Unlike previous research that focused on
      Cr(VI)-induced oxidative damage and apoptosis, this study placed emphasis on
      premature senescence that can be induced by low-dose and long-term Cr(VI)
      exposure. We found Cr(VI) induced premature senescence in L-02 hepatocytes, as
      confirmed by increase in senescence associated-beta-galactosidase (SA-beta-Gal)
      activity. Cr(VI) stabilized p53 through phosphorylation at Ser15 and increased
      expression of p53-transcriptional target p21. Mechanism study revealed Cr(VI)
      targeted and inhibited mitochondrial respiratory chain complex (MRCC) I and II to
      enhance reactive oxygen species (ROS) production. By applying antioxidant Trolox,
      we also confirmed that ROS mediated p53 activation. A tetracycline-inducible
      lentiviral expression system containing shRNA to p53 was used to knockout p53. We
      found p53 could inhibit pro-survival genes B-cell lymphoma-2 (Bcl-2), myeloid
      leukemia-1 (Mcl-1) and S phase related cell cycle proteins cyclin-dependent
      kinase 2 (CDK2), Cyclin E to induce premature senescence, and the functional role
      of ROS in Cr(VI)-induced premature senescence is depend on p53. The results
      suggest that Cr(VI) has a role in premature senescence by promoting ROS-dependent
      p53 activation in L-02 hepatocytes.

PMID- 27698450
TI  - 1,25 (OH)2D3 treatment alters the granulomatous response in M. tuberculosis
      infected mice.
AB  - Induction of cathelicidin-mediated antimicrobial pathway against intracellular M.
      tuberculosis by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of
      vitamin D, has been documented in vitro. However, in in vivo studies related to
      inflammatory disorders, 1,25(OH)2D3 has been demonstrated to induce an anti
      inflammatory response. We therefore examined whether in the murine model of
      tuberculosis, the anti-inflammatory effects of 1,25(OH)2D3 would affect the
      outcome of M. tuberculosis infection. We show here that administration of
      1,25(OH)2D3 to M. tuberculosis infected mice led to a change in lung granuloma
      architecture, characterized by a marked decrease in B cell lymphocytic
      aggregates. Consistent with the altered granulomas, 1,25(OH)2D3-treated mice also
      exhibited significantly higher bacterial burden in the lungs compared to the
      control group. These findings highlight the need to further investigate the
      effect of vitamin D on host immunity to M. tuberculosis in the context of the
      granulomatous response.

PMID- 27698451
TI  - Co-acclimation of bacterial communities under stresses of hydrocarbons with
      different structures.
AB  - Crude oil is a complex mixture of hydrocarbons with different structures; its
      components vary in bioavailability and toxicity. It is important to understand
      how bacterial communities response to different hydrocarbons and their co
      acclimation in the process of degradation. In this study, microcosms with the
      addition of structurally different hydrocarbons were setup to investigate the
      successions of bacterial communities and the interactions between different
      bacterial taxa. Hydrocarbons were effectively degraded in all microcosms after 40
      days. High-throughput sequencing offered a great quantity of data for analyzing
      successions of bacterial communities. The results indicated that the bacterial
      communities responded dramatically different to various hydrocarbons. KEGG
      database and PICRUSt were applied to predict functions of individual bacterial
      taxa and networks were constructed to analyze co-acclimations between functional
      bacterial groups. Almost all functional genes catalyzing degradation of different
      hydrocarbons were predicted in bacterial communities. Most of bacterial taxa were
      believed to conduct biodegradation processes via interactions with each other.
      This study addressed a few investigated area of bacterial community responses to
      structurally different organic pollutants and their co-acclimation and
      interactions in the process of biodegradation. The study could provide useful
      information to guide the bioremediation of crude oil pollution.

PMID- 27698452
TI  - Kupffer cells induce Notch-mediated hepatocyte conversion in a common mouse model
      of intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is a malignant epithelial neoplasm composed
      of cells resembling cholangiocytes that line the intrahepatic bile ducts in
      portal areas of the hepatic lobule. Although ICC has been defined as a tumor
      arising from cholangiocyte transformation, recent evidence from genetic lineage
      tracing experiments has indicated that hepatocytes can be a cellular origin of
      ICC by directly changing their fate to that of biliary lineage cells. Notch
      signaling has been identified as an essential factor for hepatocyte conversion
      into biliary lineage cells at the onset of ICC. However, the mechanisms
      underlying Notch signal activation in hepatocytes remain unclear. Here, using a
      mouse model of ICC, we found that hepatic macrophages called Kupffer cells
      transiently congregate around the central veins in the liver and express the
      Notch ligand Jagged-1 coincident with Notch activation in pericentral
      hepatocytes. Depletion of Kupffer cells prevents the Notch-mediated cell-fate
      conversion of hepatocytes to biliary lineage cells, inducing hepatocyte apoptosis
      and increasing mortality in mice. These findings will be useful for uncovering
      the pathogenic mechanism of ICC and developing prevenient and therapeutic
      strategies for this refractory disease.

PMID- 27698454
TI  - Self-assembled fibre optoelectronics with discrete translational symmetry.
AB  - Fibres with electronic and photonic properties are essential building blocks for
      functional fabrics with system level attributes. The scalability of thermal fibre
      drawing approach offers access to large device quantities, while constraining the
      devices to be translational symmetric. Lifting this symmetry to create discrete
      devices in fibres will increase their utility. Here, we draw, from a macroscopic
      preform, fibres that have three parallel internal non-contacting continuous
      domains; a semiconducting glass between two conductors. We then heat the fibre
      and generate a capillary fluid instability, resulting in the selective
      transformation of the cylindrical semiconducting domain into discrete spheres
      while keeping the conductive domains unchanged. The cylindrical-to-spherical
      expansion bridges the continuous conducting domains to create ~104 self
      assembled, electrically contacted and entirely packaged discrete spherical
      devices per metre of fibre. The photodetection and Mie resonance dependent
      response are measured by illuminating the fibre while connecting its ends to an
      electrical readout.

PMID- 27698453
TI  - Possible neural mechanisms of psychotherapy for trauma-related symptoms: cerebral
      responses to the neuropsychological treatment of post-traumatic stress disorder
      model individuals.
AB  - Psychotherapy is often effective for treating psychogenic disorders, but the
      changes that occur in the brain during such treatments remain unknown. To
      investigate this, we monitored cerebral activity throughout an entire session
      using a psychotherapeutic technique in healthy subjects. Since post-traumatic
      stress disorder (PTSD) is a typical psychogenic psychiatric disorder, we used
      PTSD-model volunteers who had experienced a moderately traumatic event. The
      technique used as psychotherapy was eye movement desensitisation and reprocessing
      (EMDR), a standard method for treating PTSD. The oxygenated haemoglobin
      concentration ([oxy-Hb]), a sensitive index of brain activation, measured using
      multi-channel near-infrared spectroscopy, revealed changes in [oxy-Hb] in the
      superior temporal sulcus (STS) and orbitofrontal cortex (OFC). During a vital
      therapeutic stage, a significant reduction in the activation by forced eye
      movements was observed in the right STS, and a trend toward a reduction in the
      left OFC. The hyperactivation of the right STS on the recall of unpleasant
      memories, and its normalisation by eye movements, seem to reflect an important
      neural mechanism of the psychotherapy. These findings suggest that psychotherapy
      for traumatic symptoms involves brain regions related to memory representation
      and emotion, and possibly those that link memory and emotion, such as the
      amygdala.

PMID- 27698455
TI  - Tunable Resonators for Nonlinear Modal Interactions.
AB  - Understanding the various mechanisms of nonlinear mode coupling in micro and nano
      resonators has become an imminent necessity for their successful implementation
      in practical applications. However, consistent, repeatable, and flexible
      experimental procedures to produce nonlinear mode coupling are lacking, and hence
      research into well-controlled experimental conditions is crucial. Here, we
      demonstrate well-controlled and repeatable experiments to study nonlinear mode
      coupling among micro and nano beam resonators. Such experimental approach can be
      applied to other micro and nano structures to help study their nonlinear
      interactions and exploit them for higher sensitive and less noisy responses.
      Using electrothermal tuning and electrostatic excitation, we demonstrate three
      different kinds of nonlinear interactions among the first and third bending modes
      of vibrations of slightly curved beams (arches): two-one internal resonance,
      three-one internal resonance, and mode veering (near crossing). The experimental
      procedure is repeatable, highly flexible, do not require special or precise
      fabrication, and is conducted in air and at room temperature. This approach can
      be applied to other micro and nano structures, which come naturally curved due to
      fabrication imperfections, such as CNTs, and hence lays the foundation to deeply
      investigate the nonlinear mode coupling in these structures in a consistent way.

PMID- 27698458
TI  - What determines the interfacial configuration of Nb/Al2O3 and Nb/MgO interface.
AB  - Nb films are deposited on single crystal Al2O3 (110) and MgO(111) substrates by e
      beam evaporation technique. Structure of Nb films and orientation relationships
      (ORs) of Nb/Al2O3 and Nb/MgO interface are studied and compared by the
      combination of experiments and simulations. The experiments show that the Nb
      films obtain strong (110) texture, and the Nb film on Al2O3(110) substrate shows
      a higher crystalline quality than that on MgO(111) substrate. First principle
      calculations show that both the lattice mismatch and the strength of interface
      bonding play major roles in determining the crystalline perfection of Nb films
      and ORs between Nb films and single crystal ceramic substrates. The fundamental
      mechanisms for forming the interfacial configuration in terms of the lattice
      mismatch and the strength of interface bonding are discussed.

PMID- 27698457
TI  - Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of
      HIV-1 CRF01_AE among MSM in Shanghai, China.
AB  - To explore the evolutionary dynamics and molecular transmission patterns of HIV-1
      CRF01_AE in depth among men who have sex with men (MSM) in Shanghai, we
      constructed phylogenetic tree and genetic transmission networks based on 1, 152
      pol sequences from MSM, 282 from other risk groups and 795 references.
      Phylogenetic analyses identified two distinct major CRF01_AE lineages and a
      Shanghai-based sub-lineage. The estimated tMRCAs for lineage 1 and 2 were 1996.0
      (1992.9-1999.2) and 1997.8 (1994.3-2001.4), respectively. Of the 1, 152 MSM, 681
      (59.1%) were identified as belonging to 241 separate networks. Of these 681
      individuals in networks, 74.2% were linked to cases diagnosed in different years,
      4.3% were linked to heterosexual women, and 0.7% were linked to persons who
      inject drugs. A total of 71 networks including 180 individuals diagnosed in
      Shanghai with the same domicile were found. Recent infection (P = 0.022) and
      sampling year after 2011 (P < 0.001) were significantly associated with potential
      transmission links among the networks. Besides, a significant transmission of
      viruses with drug resistant mutations at V179D/E were found in the networks.
      Given these findings, we propose that genetic transmission analysis is a useful
      tool in HIV intervention strategies to curb the spread of virus and promoting
      public health.

PMID- 27698459
TI  - Prediction of phosphothreonine sites in human proteins by fusing different
      features.
AB  - Phosphorylation is one of the most important protein post-translation
      modifications. With the rapid development of high-throughput mass spectrometry,
      phosphorylation site data is rapidly accumulating, which provides us an
      opportunity to systematically investigate and predict phosphorylation in
      proteins. The phosphorylation of threonine is the addition of a phosphoryl group
      to its polar side chains group. In this work, we statistically analyzed the
      distribution of the different properties including position conservation,
      secondary structure, accessibility and some other physicochemical properties of
      the residues surrounding the phosphothreonine site and non-phosphothreonine site.
      We found that the distributions of those features are non-symmetrical. Based on
      the distribution of properties, we developed a new model by using optimal window
      size strategy and feature selection technique. The cross-validated results show
      that the area under receiver operating characteristic curve reaches to 0.847,
      suggesting that our model may play a complementary role to other existing methods
      for predicting phosphothreonine site in proteins.

PMID- 27698456
TI  - Microbial Degradation of Cellular Kinases Impairs Innate Immune Signaling and
      Paracrine TNFalpha Responses.
AB  - The NFkappaB and MAPK signaling pathways are critical components of innate
      immunity that orchestrate appropriate immune responses to control and eradicate
      pathogens. Their activation results in the induction of proinflammatory
      mediators, such as TNFalpha a potent bioactive molecule commonly secreted by
      recruited inflammatory cells, allowing for paracrine signaling at the site of an
      infection. In this study we identified a novel mechanism by which the
      opportunistic pathogen Porphyromonas gingivalis dampens innate immune responses
      by disruption of kinase signaling and degradation of inflammatory mediators. The
      intracellular immune kinases RIPK1, TAK1, and AKT were selectively degraded by
      the P. gingivalis lysine-specific gingipain (Kgp) in human endothelial cells,
      which correlated with dysregulated innate immune signaling. Kgp was also observed
      to attenuate endothelial responsiveness to TNFalpha, resulting in a reduction in
      signal flux through AKT, ERK and NFkappaB pathways, as well as a decrease in
      downstream proinflammatory mRNA induction of cytokines, chemokines and adhesion
      molecules. A deficiency in Kgp activity negated decreases to host cell kinase
      protein levels and responsiveness to TNFalpha. Given the essential role of kinase
      signaling in immune responses, these findings highlight a unique mechanism of
      pathogen-induced immune dysregulation through inhibition of cell activation,
      paracrine signaling, and dampened cellular proinflammatory responses.

PMID- 27698460
TI  - Massive yet grossly underestimated global costs of invasive insects.
AB  - Insects have presented human society with some of its greatest development
      challenges by spreading diseases, consuming crops and damaging infrastructure.
      Despite the massive human and financial toll of invasive insects, cost estimates
      of their impacts remain sporadic, spatially incomplete and of questionable
      quality. Here we compile a comprehensive database of economic costs of invasive
      insects. Taking all reported goods and service estimates, invasive insects cost a
      minimum of US$70.0 billion per year globally, while associated health costs
      exceed US$6.9 billion per year. Total costs rise as the number of estimate
      increases, although many of the worst costs have already been estimated
      (especially those related to human health). A lack of dedicated studies,
      especially for reproducible goods and service estimates, implies gross
      underestimation of global costs. Global warming as a consequence of climate
      change, rising human population densities and intensifying international trade
      will allow these costly insects to spread into new areas, but substantial savings
      could be achieved by increasing surveillance, containment and public awareness.

PMID- 27698461
TI  - Factors controlling bark decomposition and its role in wood decomposition in five
      tropical tree species.
AB  - Organic matter decomposition represents a vital ecosystem process by which
      nutrients are made available for plant uptake and is a major flux in the global
      carbon cycle. Previous studies have investigated decomposition of different plant
      parts, but few considered bark decomposition or its role in decomposition of
      wood. However, bark can comprise a large fraction of tree biomass. We used a
      common litter-bed approach to investigate factors affecting bark decomposition
      and its role in wood decomposition for five tree species in a secondary seasonal
      tropical rain forest in SW China. For bark, we implemented a litter bag
      experiment over 12 mo, using different mesh sizes to investigate effects of
      litter meso- and macro-fauna. For wood, we compared the decomposition of branches
      with and without bark over 24 mo. Bark in coarse mesh bags decomposed 1.11-1.76
      times faster than bark in fine mesh bags. For wood decomposition, responses to
      bark removal were species dependent. Three species with slow wood decomposition
      rates showed significant negative effects of bark-removal, but there was no
      significant effect in the other two species. Future research should also
      separately examine bark and wood decomposition, and consider bark-removal
      experiments to better understand roles of bark in wood decomposition.

PMID- 27698464
TI  - Efficiency Enhancement of Hybrid Perovskite Solar Cells with MEH-PPV Hole
      Transporting Layers.
AB  - In this study, hybrid perovskite solar cells are fabricated using poly[2-methoxy
      5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) and poly(3-hexylthiophene
      2,5-diyl) (P3HT) as dopant-free hole-transporting materials (HTMs), and two
      solution processes (one- and two-step methods, respectively) for preparing
      methylammonium lead iodide perovskite. By optimizing the concentrations and
      solvents of MEH-PPV solutions, a power conversion efficiency of 9.65% with
      hysteresis-less performance is achieved, while the device with 2,2',7,7'
      tetrakis(N,N-di-p-methoxyphenylamine)-9,9'spirobifluorene (Spiro-OMeTAD) doped
      with lithium salts and tert-butylpyridine (TBP) exhibits an efficiency of 13.38%.
      This result shows that non-doped MEH-PPV is a suitable, low-cost HTM for
      efficient polymer-based perovskite solar cells. The effect of different
      morphologies of methylammonium lead iodide perovskite on conversion efficiency is
      also investigated by incident photon-to-electron conversion efficiency (IPCE)
      curves and electrochemical impedance spectroscopy (EIS).

PMID- 27698462
TI  - Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia
      by ultra deep sequencing analysis.
AB  - To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to
      require very few genetic alterations in addition to the fusion gene itself.
      Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute
      lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with
      incidences ranging from 25 to 50%. Whereas previous studies employed Sanger
      sequencing, here we used next generation amplicon deep sequencing for in depth
      evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+
      leukaemia. RAS mutations including those in small sub-clones were detected in
      63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at
      diagnosis and relapse revealed complex RAS clone dynamics and showed that the
      mutated clones present at relapse were almost all originated from clones that
      were already detectable at diagnosis and survived to the initial therapy.
      Finally, we showed that mutated patients were indeed characterized by a RAS
      related signature at both transcriptional and protein levels and that the
      targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP
      ALL clones carrying somatic RAS mutations.

PMID- 27698463
TI  - High expression of new genes in trochophore enlightening the ontogeny and
      evolution of trochozoans.
AB  - Animals with trochophore larvae belong to Trochozoa, one of the main branches of
      Bilateria. In addition to exhibiting spiral cleavage and early cell fate
      determination, trochozoans typically undergo indirect development, which
      contributes to the most unique characteristics of their ontogeny. The indirect
      development of trochozoans has provoked discussion regarding the origin and
      evolution of marine larvae and is interesting from the perspective of phylogeny
      ontogeny correspondence. While these phylo-onto correlations have an hourglass
      shape in Deuterostomia, Ecdysozoa, plants and even fungi, they have seldom been
      studied in Trochozoa, and even Lophotrochozoa. Here, we compared the ontogenetic
      transcriptomes of the Pacific oyster, Crassostrea gigas (Bivalvia, Mollusca), the
      Pacific abalone, Haliotis discus hannai (Gastropoda, Mollusca), and the sand worm
      Perinereis aibuhitensis (Polychaeta, Annelida) using several complementary
      phylotranscriptomic methods to examine their evolutionary trajectories. The
      results revealed the late trochophore stage as the phylotypic phase. However,
      this basic pattern is accompanied with increased use of new genes in the
      trochophore stages which marks specific adaptations of the larval body plans.

PMID- 27698465
TI  - The polarization modulation and fabrication method of two dimensional silica
      photonic crystals based on UV nanoimprint lithography and hot imprint.
AB  - Based on a silica sol-gel technique, highly-structurally ordered silica photonic
      structures were fabricated by UV lithography and hot manual nanoimprint efforts,
      which makes large-scale fabrication of silica photonic crystals easy and results
      in low-cost. These photonic structures show perfect periodicity, smooth and flat
      surfaces and consistent aspect ratios, which are checked by scanning electron
      microscopy (SEM) and atomic force microscopy (AFM). In addition, glass substrates
      with imprinted photonic nanostructures show good diffraction performance in both
      transmission and reflection mode. Furthermore, the reflection efficiency can be
      enhanced by 5 nm Au nanoparticle coating, which does not affect the original
      imprint structure. Also the refractive index and dielectric constant of the
      imprinted silica is close to that of the dielectric layer in nanodevices. In
      addition, the polarization characteristics of the reflected light can be
      modulated by stripe nanostructures through changing the incident light angle. The
      experimental findings match with theoretical results, making silica photonic
      nanostructures functional integration layers in many optical or optoelectronic
      devices, such as LED and microlasers to enhance the optical performance and
      modulate polarization properties in an economical and large-scale way.

PMID- 27698467
TI  - Electrodynamic study of YIG filters and resonators.
AB  - Numerical solutions of coupled Maxwell and Landau-Lifshitz-Gilbert equations for
      a magnetized yttrium iron garnet (YIG) sphere acting as a one-stage filter are
      presented. The filter is analysed using finite-difference time-domain technique.
      Contrary to the state of the art, the study shows that the maximum
      electromagnetic power transmission through the YIG filter occurs at the frequency
      of the magnetic plasmon resonance with the effective permeability of the
      gyromagnetic medium MUr ~ -2, and not at a ferromagnetic resonance frequency.
      Such a new understanding of the YIG filter operation, makes it one of the most
      commonly used single-negative plasmonic metamaterials. The frequency of maximum
      transmission is also found to weakly depend on the size of the YIG sphere. An
      analytic electromagnetic analysis of resonances in a YIG sphere is performed for
      circularly polarized electromagnetic fields. The YIG sphere is situated in a free
      space and in a large spherical cavity. The study demonstrates that both volume
      resonances and magnetic plasmon resonances can be solutions of the same
      transcendental equations.

PMID- 27698466
TI  - Structural studies of the N-terminal fragments of the WW domain: Insights into co
      translational folding of a beta-sheet protein.
AB  - Nascent proteins fold co-translationally because the folding speed and folding
      pathways are limited by the rate of ribosome biosynthesis in the living cell. In
      addition, though full-length proteins can fold all their residues during the
      folding process, nascent proteins initially fold only with the N-terminal
      residues. However, the transient structure and the co-translational folding
      pathway are not well understood. Here we report the atomic structures of a series
      of N-terminal fragments of the WW domain with increasing amino acid length.
      Unexpectedly, the structures indicate that the intermediate-length fragments take
      helical conformations even though the full-length protein has no helical regions.
      The circular dichroism spectra and theoretical calculations also support the
      crystallographic results. This suggests that the short-range interactions are
      more decisive in the structure formation than the long-range interactions for
      short nascent proteins. In the course of the peptide extension, the helical
      structure change to the structure mediated by the long-range interactions at a
      particular polypeptide length. Our results will provide unique information for
      elucidating the nature of co-translational folding.

PMID- 27698468
TI  - Na+ compartmentalization related to salinity stress tolerance in upland cotton
      (Gossypium hirsutum) seedlings.
AB  - The capacity for ion compartmentalization among different tissues and cells is
      the key mechanism regulating salt tolerance in plants. In this study, we
      investigated the ion compartmentalization capacity of two upland cotton genotypes
      with different salt tolerances under salt shock at the tissue, cell and molecular
      levels. We found that the leaf glandular trichome could secrete more salt ions in
      the salt-tolerant genotype than in the sensitive genotype, demonstrating the
      excretion of ions from tissue may be a new mechanism to respond to short-term
      salt shock. Furthermore, an investigation of the ion distribution demonstrated
      that the ion content was significantly lower in critical tissues and cells of the
      salt-tolerant genotype, indicating the salt-tolerant genotype had a greater
      capacity for ion compartmentalization in the shoot. By comparing the membrane H+
      ATPase activity and the expression of ion transportation-related genes, we found
      that the H+-ATPase activity and Na+/H+ antiporter are the key factors determining
      the capacity for ion compartmentalization in leaves, which might further
      determine the salt tolerance of cotton. The novel function of the glandular
      trichome and the comparison of Na+ compartmentalization between two cotton
      genotypes with contrasting salt tolerances provide a new understanding of the
      salt tolerance mechanism in cotton.

PMID- 27698469
TI  - High-resolution 3D volumetry versus conventional measuring techniques for the
      assessment of experimental lymphedema in the mouse hindlimb.
AB  - Secondary lymphedema is a common complication of cancer treatment characterized
      by chronic limb swelling with interstitial inflammation. The rodent hindlimb is a
      widely used model for the evaluation of novel lymphedema treatments. However, the
      assessment of limb volume in small animals is challenging. Recently, high
      resolution three-dimensional (3D) imaging modalities have been introduced for
      rodent limb volumetry. In the present study we evaluated the validity of
      microcomputed tomography (MUCT), magnetic resonance imaging (MRI) and ultrasound
      in comparison to conventional measuring techniques. For this purpose, acute
      lymphedema was induced in the mouse hindlimb by a modified popliteal
      lymphadenectomy. The 4-week course of this type of lymphedema was first assessed
      in 6 animals. In additional 12 animals, limb volumes were analyzed by MUCT, 9.4 T
      MRI and 30 MHz ultrasound as well as by planimetry, circumferential length and
      paw thickness measurements. Interobserver correlation was high for all
      modalities, in particular for MUCT analysis (r = 0.975, p < 0.001). Importantly,
      caliper-measured paw thickness correlated well with MUCT (r = 0.861), MRI (r =
      0.821) and ultrasound (r = 0.800). Because the assessment of paw thickness
      represents a time- and cost-effective approach, it may be ideally suited for the
      quantification of rodent hindlimb lymphedema.

PMID- 27698470
TI  - Exome sequencing in the knockin mice generated using the CRISPR/Cas system.
AB  - Knockin (KI) mouse carrying a point mutation has been an invaluable tool for
      disease modeling and analysis. Genome editing technologies using the CRISPR/Cas
      system has emerged as an alternative way to create KI mice. However, if the mice
      carry nucleotide insertions and/or deletions (InDels) in other genes, which could
      have unintentionally occurred during the establishment of the KI mouse line and
      potentially have larger impact than a point mutation, it would confound
      phenotyping of the KI mice. In this study, we performed whole exome sequencing of
      multiple lines of F1 heterozygous Ntrk1 KI mice generated using the CRISPR/Cas
      system in comparison to that of a wild-type mouse used as a control. We found
      three InDels in four KI mice but not in a control mouse. In vitro digestion assay
      suggested that each InDel occurred as a de novo mutation, was carried-over from
      the parental mice, or was incorporated through the Cas9 nuclease mediated off
      target cleavage. These results suggest that frequency of InDels found in KI mice
      generated by the CRISPR/Cas technology is not high, but cannot be neglected and
      careful assessment of these mutations is warranted.

PMID- 27698472
TI  - Quantifying yield behaviour in metals by X-ray nanotomography.
AB  - Nanoindentation of engineering materials is commonly used to study, at small
      length scales, the continuum mechanical properties of elastic modulus and yield
      strength. However, it is difficult to measure strain hardening via
      nanoindentation. Strain hardening, which describes the increase in strength with
      plastic deformation, affects fracture toughness and ductility, and is an
      important engineering material property. The problem is that the load
      displacement data of a single nanoindentation do not provide a unique solution
      for the material's plastic properties, which can be described by its stress
      strain behaviour. Three-dimensional mapping of the displacement field beneath the
      indentation provides additional information that can overcome this difficulty. We
      have applied digital volume correlation of X-ray nano-tomographs of a
      nanoindentation to measure the sub-surface displacement field and so obtain the
      plastic properties of a nano-structured oxide dispersion strengthened steel. This
      steel has potential applications in advanced nuclear energy systems, and this
      novel method could characterise samples where proton irradiation of the surface
      simulates the effects of fast neutron damage, since facilities do not yet exist
      that can replicate this damage in bulk materials.

PMID- 27698471
TI  - Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.
AB  - Tumour resistance to radiotherapy remains a barrier to improving cancer patient
      outcomes. To overcome radioresistance, certain drugs have been found to sensitize
      cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs
      should increase tumour kill and improve patient outcomes. In practice, clinical
      utility of potent radiosensitizing drugs is curtailed by off-target side effects.
      Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies
      selectively radiosensitize to tumours based on surface receptor expression. While
      two classes of potent anti-tubulins, auristatins and maytansinoids,
      indiscriminately radiosensitize tumour cells, conjugating these potent anti
      tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of
      translational significance, we report that a clinically used maytansinoid ADC,
      ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target
      expressing HER2+ tumours but not target negative tumours. In contrast to ErbB
      signal inhibition, our findings establish an alternative therapeutic paradigm for
      ErbB-based radiosensitization using antibodies to restrict radiosensitizer
      delivery.

PMID- 27698473
TI  - Apocynin and Nox2 regulate NF-kappaB by modifying thioredoxin-1 redox-state.
AB  - The reactive-oxygen-species-(ROS)-generating-enzyme Nox2 is essential for
      leukocyte anti-microbial activity. However its role in cellular redox homeostasis
      and, consequently, in modulating intracellular signaling pathways remains
      unclear. Herein, we show Nox2 activation favors thioredoxin-1 (TRX-1)/p40phox
      interaction, which leads to exclusion of TRX-1 from the nucleus. In contrast, the
      genetic deficiency of Nox2 or its pharmacological inhibition with apocynin (APO)
      results in reductive stress after lipopolysaccharide-(LPS)-cell stimulation,
      which causes nuclear accumulation of TRX-1 and enhanced transcription of
      inflammatory mediators through nuclear-factor-(NF)-kappaB. The NF-kappaB
      overactivation is prevented by TRX-1 oxidation using inhibitors of thioredoxin
      reductase-1 (TrxR-1). The Nox2/TRX-1/NF-kappaB intracellular signaling pathway is
      involved in the pathophysiology of chronic granulomatous disease (CGD) and
      sepsis. In fact, TrxR-1 inhibition prevents nuclear accumulation of TRX-1 and LPS
      stimulated hyperproduction of tumor-necrosis-factor-(TNF)-alpha by monocytes and
      neutrophils purified from blood of CGD patients, who have deficient Nox2
      activity. TrxR-1 inhibitors, either lanthanum chloride (LaCl3) or auranofin
      (AUR), also increase survival rates of mice undergoing cecal-ligation-and
      puncture-(CLP). Therefore, our results identify a hitherto unrecognized Nox2
      mediated intracellular signaling pathway that contributes to hyperinflammation in
      CGD and in septic patients. Additionally, we suggest that TrxR-1 inhibitors could
      be potential drugs to treat patients with sepsis, particularly in those with CGD.

PMID- 27698474
TI  - Structure of ubiquitylated-Rpn10 provides insight into its autoregulation
      mechanism.
AB  - Ubiquitin receptors decode ubiquitin signals into many cellular responses.
      Ubiquitin receptors also undergo coupled monoubiquitylation, and rapid
      deubiquitylation has hampered the characterization of the ubiquitylated state.
      Using bacteria that express a ubiquitylation apparatus, we purified and
      determined the crystal structure of the proteasomal ubiquitin-receptor Rpn10 in
      its ubiquitylated state. The structure shows a novel ubiquitin-binding patch that
      directs K84 ubiquitylation. Superimposition of ubiquitylated-Rpn10 onto electron
      microscopy models of proteasomes indicates that the Rpn10-conjugated ubiquitin
      clashes with Rpn9, suggesting that ubiquitylation might be involved in releasing
      Rpn10 from the proteasome. Indeed, ubiquitylation on immobilized proteasomes
      dissociates the modified Rpn10 from the complex, while unmodified Rpn10 mainly
      remains associated. In vivo experiments indicate that contrary to wild type,
      Rpn10-K84R is stably associated with the proteasomal subunit Rpn9. Similarly
      Rpn10, but not ubiquitylated-Rpn10, binds Rpn9 in vitro. Thus we suggest that
      ubiquitylation functions to dissociate modified ubiquitin receptors from their
      targets, a function that promotes cyclic activity of ubiquitin receptors.

PMID- 27698476
TI  - Wavelength-scale light concentrator made by direct 3D laser writing of polymer
      metamaterials.
AB  - We report on the realization of functional infrared light concentrators based on
      a thick layer of air-polymer metamaterial with controlled pore size gradients.
      The design features an optimum gradient index profile leading to light focusing
      in the Fresnel zone of the structures for two selected operating wavelength
      domains near 5.6 and 10.4 MUm. The metamaterial which consists in a thick polymer
      containing air holes with diameters ranging from lambda/20 to lambda/8 is made
      using a 3D lithography technique based on the two-photon polymerization of a
      homemade photopolymer. Infrared imaging of the structures reveals a tight
      focusing for both structures with a maximum local intensity increase by a factor
      of 2.5 for a concentrator volume of 1.5 lambda3, slightly limited by the residual
      absorption of the selected polymer. Such porous and flat metamaterial structures
      offer interesting perspectives to increase infrared detector performance at the
      pixel level for imaging or sensing applications.

PMID- 27698475
TI  - One-Pot Approach to Prepare Organo-silica Hybrid Capillary Monolithic Column with
      Intact Mesoporous Silica Nanoparticle as Building Block.
AB  - A facile "one-pot" approach to prepare organo-silica hybrid capillary monolithic
      column with intact mesoporous silica nanoparticle (IMSN) as crosslinker and
      building block was described. An IMSN crosslinked octadecyl-silica hybrid
      capillary monolithic column (IMSN-C18 monolithic column) was successfully
      prepared, and the effects of fabrication conditions (e.g. concentration of intact
      mesoporous silica nanoparticle, polycondensation temperature, content of
      vinyltrimethoxysilane and stearyl methacrylate) on the structures of the IMSN-C18
      monolithic column were studied in detail. The IMSN-C18 hybrid monolithic column
      possessed uniform morphology, good mechanical and pH stability (pH 1.1-11), which
      was applied to the separations of alkyl benzenes, polycyclic aromatic
      hydrocarbons (PAHs), as well as proteins. The minimum plate height of 10.5 MUm
      (corresponding to 95000 N m-1) for butylbenzene and high reproducibility were
      achieved. The analysis of tryptic digest of bovine serum albumin (BSA) was
      carried out on the IMSN-C18 monolithic column by cLC coupled mass spectrometry
      (cLC-MS/MS), with the protein sequence coverage of 87.5% for BSA, demonstrating
      its potential application in proteomics.

PMID- 27698477
TI  - A novel injectable BRET-based in vivo imaging probe for detecting the activity of
      hypoxia-inducible factor regulated by the ubiquitin-proteasome system.
AB  - The ubiquitin-proteasome system (UPS) is a selective protein degradation system
      that plays a critical role in many essential biological processes by regulating
      the existence of various cellular proteins. The target proteins of UPS are
      recognized and tagged with polyubiquitin chains by E3 ubiquitin ligases, which
      have high substrate-specific activities. Here we present a novel injectable
      imaging probe POL-N that can detect the UPS-regulated hypoxia-inducible factor
      (HIF) activity in vivo. Because the luciferase is fused to the E3 ligase
      recognition domain of the HIF-1alpha, POL-N is intact only in the HIFalpha
      overexpressing cells, that is, HIF-active cells, generating signals via an
      intramolecular bioluminescence resonance energy transfer (BRET) between
      luciferase and a near-infrared (NIR) fluorescent dye at the C-terminal end of the
      probe. Off-target signals of the NIR-BRET were so low that we could achieve
      highly sensitive and fast detection of intratumoral HIF-activity. Notably, we
      successfully detected hypoxic liver metastasis, which is extremely difficult to
      detect by injectable imaging probes due to strong off-target signals, as early as
      1 h after systemic injection of POL-N. Our probe design can be widely adapted to
      UPS-target proteins and may contribute to the exploration of their roles in
      animal disease models.

PMID- 27698478
TI  - Oscillating edge states in one-dimensional MoS2 nanowires.
AB  - Reducing the dimensionality of transition metal dichalcogenides to one dimension
      opens it to structural and electronic modulation related to charge density wave
      and quantum correlation effects arising from edge states. The greater flexibility
      of a molecular scale nanowire allows a strain-imposing substrate to exert
      structural and electronic modulation on it, leading to an interplay between the
      curvature-induced influences and intrinsic ground-state topology. Herein, the
      templated growth of MoS2 nanowire arrays consisting of the smallest
      stoichiometric MoS2 building blocks is investigated using scanning tunnelling
      microscopy and non-contact atomic force microscopy. Our results show that lattice
      strain imposed on a nanowire causes the energy of the edge states to oscillate
      periodically along its length in phase with the period of the substrate
      topographical modulation. This periodic oscillation vanishes when individual MoS2
      nanowires join to form a wider nanoribbon, revealing that the strain-induced
      modulation depends on in-plane rigidity, which increases with system size.

PMID- 27698479
TI  - Multiphoton imaging reveals that nanosecond pulsed electric fields collapse tumor
      and normal vascular perfusion in human glioblastoma xenografts.
AB  - Despite the biomedical advances of the last century, many cancers including
      glioblastoma are still resistant to existing therapies leaving patients with poor
      prognoses. Nanosecond pulsed electric fields (nsPEF) are a promising technology
      for the treatment of cancer that have thus far been evaluated in vitro and in
      superficial malignancies. In this paper, we develop a tumor organoid model of
      glioblastoma and apply intravital multiphoton microscopy to assess their response
      to nsPEFs. We demonstrate for the first time that a single 10 ns, high voltage
      electric pulse (35-45 kV/cm), collapses the perfusion of neovasculature, and also
      alters the diameter of capillaries and larger vessels in normal tissue. These
      results contribute to the fundamental understanding of nsPEF effects in complex
      tissue environments, and confirm the potential of nsPEFs to disrupt the
      microenvironment of solid tumors such as glioblastoma.

PMID- 27698481
TI  - Hydrogen-bonding Interactions between Apigenin and Ethanol/Water: A Theoretical
      Study.
AB  - In this work, hydrogen-bonding interactions between apigenin and water/ethanol
      were investigated from a theoretical perspective using quantum chemical
      calculations. Two conformations of apigenin molecule were considered in this
      work. The following results were found. (1) For apigenin monomer, the molecular
      structure is non-planar, and all of the hydrogen and oxygen atoms can be hydrogen
      bonding sites. (2) Eight and seven optimized geometries are obtained for apigenin
      (I)-H2O/CH3CH2OH and apigenin (II)-H2O/CH3CH2OH complexes, respectively. In
      apigenin, excluding the aromatic hydrogen atoms in the phenyl substituent, all
      other hydrogen atoms and the oxygen atoms form hydrogen-bonds with H2O and
      CH3CH2OH. (3) In apigenin-H2O/CH3CH2OH complexes, the electron density and the
      E(2) in the related localized anti-bonding orbital are increased upon hydrogen
      bond formation. These are the cause of the elongation and red-shift of the X-H
      bond. The sum of the charge change transfers from the hydrogen-bond acceptor to
      donor. The stronger interaction makes the charge change more intense than in the
      less stable structures. (4) Most of the hydrogen-bonds in the complexes are
      electrostatic in nature. However, the C4-O5...H, C9-O4...H and C13-O2...H
      hydrogen-bonds have some degree of covalent character. Furthermore, the hydroxyl
      groups of the apigenin molecule are the preferred hydrogen-bonding sites.

PMID- 27698480
TI  - Mode of renal replacement therapy determines endotoxemia and neutrophil
      dysfunction in chronic kidney disease.
AB  - Bacterial infection and sepsis are common complications of chronic kidney disease
      (CKD). A vicious cycle of increased gut permeability, endotoxemia, inadequate
      activation of the innate immune system and resulting innate immune dysfunction is
      hypothesized. We assessed endotoxemia, neutrophil function and its relation to
      oxidative stress, inflammation and gut permeability in patients with CKD grade 3
      5 without renal replacement therapy (CKD group, n = 57), patients with CKD stage
      5 undergoing haemodialysis (HD, n = 32) or peritoneal dialysis (PD, n = 28) and
      patients after kidney transplantation (KT, n = 67) in a cross-sectional
      observational study. In HD patients, endotoxin serum levels were elevated and
      neutrophil phagocytic capacity was decreased compared to all other groups.
      Patients on HD had a significantly higher mortality, due to infections during
      follow up, compared to PD (p = 0.022). Oxidative stress, neutrophil energy
      charge, systemic inflammation and gut permeability could not completely explain
      these differences. Our findings suggest that dialysis modality and not renal
      function per se determine the development of neutrophil dysfunction and
      endotoxemia in CKD-patients. HD patients are particularly prone to neutrophil
      dysfunction and endotoxemia whereas neutrophil function seems to improve after
      KT. Multi-target approaches are therefore warranted to improve neutrophil
      function and potentially reduce the rate of infections with patients undergoing
      haemodialysis.

PMID- 27698482
TI  - Elevation in fibroblast growth factor 23 and its value for identifying
      subclinical atherosclerosis in first-degree relatives of patients with diabetes.
AB  - Accumulating evidence supported an association between diabetes and fibroblast
      growth factor 23 (FGF23). The goal of the present study was to explore alteration
      in serum FGF23 levels and to assess its value for identifying subclinical
      atherosclerosis in normoglycemic individuals with a first-degree family history
      of diabetes (FHD). The study enrolled 312 subjects with a first-degree FHD and
      1407 subjects without an FHD. Serum FGF23 levels were detected by a sandwich
      enzyme-linked immunosorbent assay. Serum FGF23 levels were much higher in
      subjects with a first-degree FHD than in those without an FHD (P = 0.006). A
      first-degree FHD was positively associated with serum FGF23 levels, independent
      of C-IMT and cardiovascular factors (both P < 0.05). In subjects with a first
      degree FHD, only those with serum FGF23 levels in the upper quartile were more
      likely to have an increased C-IMT (odds ratio = 2.263, P < 0.05). As conclusions,
      a first-degree FHD contributes to the increased serum FGF23 levels independently.
      Subjects with a first-degree FHD need higher serum FGF23 levels to indicate
      subclinical atherosclerosis. The influence of a first-degree FHD on serum FGF23
      levels should be considered to avoid overestimating the risk of cardiovascular
      disease in normoglycemic individuals with a first-degree FHD.

PMID- 27698483
TI  - Comparative and parallel genome-wide association studies for metabolic and
      agronomic traits in cereals.
AB  - The plant metabolome is characterized by extensive diversity and is often
      regarded as a bridge between genome and phenome. Here we report metabolic and
      phenotypic genome-wide studies (mGWAS and pGWAS) in rice grain that, in addition
      to previous metabolic GWAS in rice leaf and maize kernel, show both distinct and
      overlapping aspects of genetic control of metabolism within and between species.
      We identify new candidate genes potentially influencing important metabolic
      and/or morphological traits. We show that the differential genetic architecture
      of rice metabolism between different tissues is in part determined by tissue
      specific expression. Using parallel mGWAS and pGWAS we identify new candidate
      genes potentially responsible for variation in traits such as grain colour and
      size, and provide evidence of metabotype-phenotype linkage. Our study
      demonstrates a powerful strategy for interactive functional genomics and
      metabolomics in plants, especially the cloning of minor QTLs for complex
      phenotypic traits.

PMID- 27698484
TI  - Measuring cell surface area and deformability of individual human red blood cells
      over blood storage using quantitative phase imaging.
AB  - The functionality and viability of stored human red blood cells (RBCs) is an
      important clinical issue in transfusions. To systematically investigate changes
      in stored whole blood, the hematological properties of individual RBCs were
      quantified in blood samples stored for various periods with and without a
      preservation solution called citrate phosphate dextrose adenine-1 (CPDA-1). With
      3-D quantitative phase imaging techniques, the optical measurements for 3-D
      refractive index (RI) distributions and membrane fluctuations were done at the
      individual cell level. From the optical measurements, the morphological (volume,
      surface area and sphericity), biochemical (hemoglobin content and concentration),
      and mechanical parameters (dynamic membrane fluctuation) were simultaneously
      quantified to investigate the functionalities and progressive alterations of
      stored RBCs. Our results show that stored RBCs without CPDA-1 had a dramatic
      morphological transformation from discocytes to spherocytes within two weeks
      which was accompanied by significant decreases in cell deformability and cell
      surface area, and increases in sphericity. However, the stored RBCs with CPDA-1
      maintained their morphology and deformability for up to 6 weeks.

PMID- 27698485
TI  - Applying high-resolution melting (HRM) technology to identify five commonly used
      Artemisia species.
AB  - Many members of the genus Artemisia are important for medicinal purposes with
      multiple pharmacological properties. Often, these herbal plants sold on the
      markets are in processed forms so it is difficult to authenticate. Routine
      testing and identification of these herbal materials should be performed to
      ensure that the raw materials used in pharmaceutical products are suitable for
      their intended use. In this study, five commonly used Artemisia species included
      Artemisia argyi, Artemisia annua, Artemisia lavandulaefolia, Artemisia indica,
      and Artemisia atrovirens were analyzed using high resolution melting (HRM)
      analysis based on the internal transcribed spacer 2 (ITS2) sequences. The melting
      profiles of the ITS2 amplicons of the five closely related herbal species are
      clearly separated so that they can be differentiated by HRM method. The method
      was further applied to authenticate commercial products in powdered. HRM curves
      of all the commercial samples tested are similar to the botanical species as
      labeled. These congeneric medicinal products were also clearly separated using
      the neighbor-joining (NJ) tree. Therefore, HRM method could provide an efficient
      and reliable authentication system to distinguish these commonly used Artemisia
      herbal products on the markets and offer a technical reference for medicines
      quality control in the drug supply chain.

PMID- 27698486
TI  - Similar contrast sensitivity functions measured using psychophysics and
      optokinetic nystagmus.
AB  - Although the contrast sensitivity function (CSF) is a particularly useful way of
      characterising functional vision, its measurement relies on observers making
      reliable perceptual reports. Such procedures can be challenging when testing
      children. Here we describe a system for measuring the CSF using an automated
      analysis of optokinetic nystagmus (OKN); an involuntary oscillatory eye movement
      made in response to drifting stimuli, here spatial-frequency (SF) band-pass
      noise. Quantifying the strength of OKN in the stimulus direction allows us to
      estimate contrast sensitivity across a range of SFs. We compared the CSFs of 30
      observers with normal vision measured using both OKN and perceptual report. The
      approaches yield near-identical CSFs (mean R = 0.95) that capture subtle intra
      observer variations in visual acuity and contrast sensitivity (both R = 0.84, p <
      0.0001). Trial-by-trial analysis reveals high correlation between OKN and
      perceptual report, a signature of a common neural mechanism for determining
      stimulus direction. We also observe conditions where OKN and report are
      significantly decorrelated as a result of a minority of observers experiencing
      direction-reversals that are not reflected by OKN. We conclude that there are a
      wide range of stimulus conditions for which OKN can provide a valid alternative
      means of measuring of the CSF.

PMID- 27698487
TI  - Enantioselective desymmetrization of cyclohexadienones via an intramolecular
      Rauhut-Currier reaction of allenoates.
AB  - The Rauhut-Currier (RC) reaction represents an efficient method for the
      construction of carbon-carbon bond in organic synthesis. However, the RC
      reactions involving allenoate substrates are very rare, and in particular,
      asymmetric intramolecular RC reaction of allenoates is yet to be discovered.
      Here, we show that the intramolecular RC reaction proceeds smoothly in the
      presence of 1 mol% beta-ICD, and bicyclic lactones are obtained in high yields
      and with excellent enantiomeric excesses. With the employment of gamma
      substituted allenoates as racemic precursors, a novel dynamic kinetic resolution
      of allenes via RC reaction is observed, which allows for facile synthesis of
      highly enantiomerically enriched allenes.

PMID- 27698488
TI  - Insights into cancer severity from biomolecular interaction mechanisms.
AB  - To attain a deeper understanding of diseases like cancer, it is critical to
      couple genetics with biomolecular mechanisms. High-throughput sequencing has
      identified thousands of somatic mutations across dozens of cancers, and there is
      a pressing need to identify the few that are pathologically relevant. Here we use
      protein structure and interaction data to interrogate nonsynonymous somatic
      cancer mutations, identifying a set of 213 molecular interfaces (protein-protein,
      -small molecule or -nucleic acid) most often perturbed in cancer, highlighting
      several potentially novel cancer genes. Over half of these interfaces involve
      protein-small-molecule interactions highlighting their overall importance in
      cancer. We found distinct differences in the predominance of perturbed interfaces
      between cancers and histological subtypes and presence or absence of certain
      interfaces appears to correlate with cancer severity.

PMID- 27698490
TI  - A fossil biting midge (Diptera: Ceratopogonidae) from early Eocene Indian amber
      with a complex pheromone evaporator.
AB  - The life-like fidelity of organisms captured in amber is unique among all kinds
      of fossilization and represents an invaluable source for different fields of
      palaeontological and biological research. One of the most challenging aspects in
      amber research is the study of traits related to behaviour. Here, indirect
      evidence for pheromone-mediated mating behaviour is recorded from a biting midge
      (Ceratopogonidae) in 54 million-year-old Indian amber. Camptopterohelea odora n.
      sp. exhibits a complex, pocket shaped structure on the wings, which resembles the
      wing folds of certain moth flies (Diptera: Psychodidae) and scent organs that are
      only known from butterflies and moths (Lepidoptera) so far. Our studies suggests
      that pheromone releasing structures on the wings have evolved independently in
      biting midges and might be much more widespread in fossil as well as modern
      insects than known so far.

PMID- 27698489
TI  - Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to
      psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue
      repair. Mutant mice modeling psoriasis skin characteristics have provided useful
      information relevant to molecular mechanisms and could serve to evaluate
      therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was
      markedly induced during tissue repair in mice. Analysis of mice overexpressing
      ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6
      activity promotes aberrant epidermal barrier function due to hyperproliferation
      of prematurely differentiated keratinocytes. Moreover, skin tissues of K14
      Angptl6 Tg mice showed aberrantly activated skin tissue inflammation seen in
      psoriasis. Levels of the proteins S100A9, recently proposed as therapeutic
      targets for psoriasis, also increased in skin tissue of K14-Angptl6 Tg mice, but
      psoriasis-like inflammatory phenotypes in those mice were not rescued by S100A9
      deletion. This finding suggests that decreasing S100A9 levels may not ameliorate
      all cases of psoriasis and that diverse mechanisms underlie the condition.
      Finally, we observed enhanced levels of epidermal ANGPTL6 in tissue specimens
      from some psoriasis patients. We conclude that the K14-Angptl6 Tg mouse is useful
      to investigate psoriasis pathogenesis and for preclinical testing of new
      therapeutics. Our study also suggests that ANGPTL6 activation in keratinocytes
      enhances psoriasis susceptibility.

PMID- 27698492
TI  - First Direct Evidence of Long-distance Seasonal Movements and Hibernation in a
      Migratory Bat.
AB  - Understanding of migration in small bats has been constrained by limitations of
      techniques that were labor-intensive, provided coarse levels of resolution, or
      were limited to population-level inferences. Knowledge of movements and behaviors
      of individual bats have been unknowable because of limitations in size of
      tracking devices and methods to attach them for long periods. We used sutures to
      attach miniature global positioning system (GPS) tags and data loggers that
      recorded light levels, activity, and temperature to male hoary bats (Lasiurus
      cinereus). Results from recovered GPS tags illustrated profound differences among
      movement patterns by individuals, including one that completed a >1000 km round
      trip journey during October 2014. Data loggers allowed us to record sub-hourly
      patterns of activity and torpor use, in one case over a period of 224 days that
      spanned an entire winter. In this latter bat, we documented 5 torpor bouts that
      lasted >=16 days and a flightless period that lasted 40 nights. These first uses
      of miniature tags on small bats allowed us to discover that male hoary bats can
      make multi-directional movements during the migratory season and sometimes
      hibernate for an entire winter.

PMID- 27698493
TI  - Printed 2 V-operating organic inverter arrays employing a small-molecule/polymer
      blend.
AB  - Printed organic thin-film transistors (OTFTs) are well suited for low-cost
      electronic applications, such as radio frequency identification (RFID) tags and
      sensors. Achieving both high carrier mobility and uniform electrical
      characteristics in printed OTFT devices is essential in these applications. Here,
      we report on printed high-performance OTFTs and circuits using silver
      nanoparticle inks for the source/drain electrodes and a blend of dithieno[2,3
      d;2',3'-d']benzo[1,2-b;4,5-b']dithiophene (DTBDT-C6) and polystyrene for the
      organic semiconducting layer. A high saturation region mobility of 1.0 cm2 V-1 s
      1 at low operation voltage of -5 V was obtained for relatively short channel
      lengths of 9 MUm. All fifteen of the printed pseudo-CMOS inverter circuits were
      formed on a common substrate and operated at low operation voltage of 2 V with
      the total variation in threshold voltage of 0.35 V. Consequently, the printed
      OTFT devices can be used in more complex integrated circuit applications
      requiring low manufacturing cost over large areas.

PMID- 27698491
TI  - Escherichia coli Braun Lipoprotein (BLP) exhibits endotoxemia - like pathology in
      Swiss albino mice.
AB  - The endotoxin lipopolysaccharide (LPS) promotes sepsis, but bacterial peptides
      also promote inflammation leading to sepsis. We found, intraperitoneal
      administration of live or heat inactivated E. coli JE5505 lacking the abundant
      outer membrane protein, Braun lipoprotein (BLP), was less toxic than E. coli
      DH5alpha possessing BLP in Swiss albino mice. Injection of BLP free of LPS
      purified from E. coli DH5alpha induced massive infiltration of leukocytes in
      lungs and liver. BLP activated human polymorphonuclear cells (PMNs) ex vivo to
      adhere to denatured collagen in serum and polymyxin B independent fashion, a
      property distinct from LPS. Both LPS and BLP stimulated the synthesis of platelet
      activating factor (PAF), a potent lipid mediator, in human PMNs. In mouse
      macrophage cell line, RAW264.7, while both BLP and LPS similarly upregulated TNF
      alpha and IL-1beta mRNA; BLP was more potent in inducing cyclooxygenase-2 (COX-2)
      mRNA and protein expression. Peritoneal macrophages from TLR2-/- mice
      significantly reduced the production of TNF-alpha in response to BLP in contrast
      to macrophages from wild type mice. We conclude, BLP acting through TLR2, is a
      potent inducer of inflammation with a response profile both common and distinct
      from LPS. Hence, BLP mediated pathway may also be considered as an effective
      target against sepsis.

PMID- 27698496
TI  - Surrogate Markers and Drug Approvals.

PMID- 27698495
TI  - The Oncoprotein BRD4-NUT Generates Aberrant Histone Modification Patterns.
AB  - Defects in chromatin proteins frequently manifest in diseases. A striking case of
      a chromatin-centric disease is NUT-midline carcinoma (NMC), which is
      characterized by expression of NUT as a fusion partner most frequently with BRD4.
      ChIP-sequencing studies from NMC patients revealed that BRD4-NUT (B4N) covers
      large genomic regions and elevates transcription within these domains. To
      investigate how B4N modulates chromatin, we performed affinity purification of
      B4N when ectopically expressed in 293-TREx cells and quantified the associated
      histone posttranslational modifications (PTM) using proteomics. We observed
      significant enrichment of acetylation particularly on H3 K18 and of combinatorial
      patterns such as H3 K27 acetylation paired with K36 methylation. We postulate
      that B4N complexes override the preexisting histone code with new PTM patterns
      that reflect aberrant transcription and that epigenetically modulate the
      nucleosome environment toward the NMC state.

PMID- 27698497
TI  - Predicting Success in Residency: The Quarterback Problem.

PMID- 27698494
TI  - Regulation of the Abundance of Kaposi's Sarcoma-Associated Herpesvirus ORF50
      Protein by Oncoprotein MDM2.
AB  - The switch between latency and the lytic cycle of Kaposi's sarcoma-associated
      herpesvirus (KSHV) is controlled by the expression of virally encoded ORF50
      protein. Thus far, the regulatory mechanism underlying the protein stability of
      ORF50 is unknown. Our earlier studies have demonstrated that a protein abundance
      regulatory signal (PARS) at the ORF50 C-terminal region modulates its protein
      abundance. The PARS region consists of PARS-I (aa 490-535) and PARS-II (aa 590
      650), and mutations in either component result in abundant expression of ORF50.
      Here, we show that ORF50 protein is polyubiquitinated and its abundance is
      controlled through the proteasomal degradation pathway. The PARS-I motif mainly
      functions as a nuclear localization signal in the control of ORF50 abundance,
      whereas the PARS-II motif is required for the binding of ubiquitin enzymes in the
      nucleus. We find that human oncoprotein MDM2, an ubiquitin E3 ligase, is capable
      of interacting with ORF50 and promoting ORF50 degradation in cells. The
      interaction domains between both proteins are mapped to the PARS region of ORF50
      and the N-terminal 220-aa region of MDM2. Additionally, we identify lysine
      residues at positions 152 and 154 in the N-terminal domain of ORF50 critically
      involved in MDM2-mediated downregulation of ORF50 levels. Within KSHV-infected
      cells, the levels of MDM2 were greatly reduced during viral lytic cycle and
      genetic knockdown of MDM2 in these cells favored the enhancement of ORF50
      expression, supporting that MDM2 is a negative regulator of ORF50 expression.
      Collectively, the study elucidates the regulatory mechanism of ORF50 stability
      and implicates that MDM2 may have a significant role in the maintenance of viral
      latency by lowering basal level of ORF50.

PMID- 27698498
TI  - Prescribing Errors with Levetiracetam Oral Solution; Communicate Insulin Dose and
      Concentration on Separate Lines; Risperidone and Ropinirole Mix-ups; IV Line
      Disinfection Caps Can Become Foreign Bodies.
AB  - These medication errors have occurred in health care facilities at least once.
      They will happen again-perhaps where you work. Through education and alertness of
      personnel and procedural safeguards, they can be avoided. You should consider
      publishing accounts of errors in your newsletters and/or presenting them at your
      inservice training programs. Your assistance is required to continue this
      feature. The reports described here were received through the Institute for Safe
      Medication Practices (ISMP) Medication Errors Reporting Program. Any reports
      published by ISMP will be anonymous. Comments are also invited; the writers'
      names will be published if desired. ISMP may be contacted at the address shown
      below. Errors, close calls, or hazardous conditions may be reported directly to
      ISMP through the ISMP Web site (www.ismp.org), by calling 800-FAIL-SAFE, or via e
      mail at ismpinfo@ismp.org. ISMP guarantees the confidentiality and security of
      the information received and respects reporters' wishes as to the level of detail
      included in publications.

PMID- 27698499
TI  - Ipilimumab-Induced Polyneuropathy; Ibuprofen-Induced Allergic-Type Liver Injury;
      Trimethoprim-Sulfamethoxazole-Induced Immune Thrombocytopenia in Children; Mesna
      Induced Fixed Drug Eruption; Digoxin-Induced Ocular Toxicity.
AB  - The purpose of this feature is to heighten awareness of specific adverse drug
      reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to
      the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If
      you have reported an interesting, preventable ADR to MedWatch, please consider
      sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside
      Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail:
      mmancano@temple.edu). Your report will be published anonymously unless otherwise
      requested. This feature is provided by the Institute for Safe Medication
      Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple
      University School of Pharmacy. ISMP is an FDA MedWatch partner.

PMID- 27698500
TI  - Arsenic Trioxide and Tretinoin (AsO/ATRA) for Acute Promyelocytic Leukemia (APL).
AB  - The complexity of cancer chemotherapy requires pharmacists be familiar with the
      complicated regimens and highly toxic agents used. This column reviews various
      issues related to preparation, dispensing, and administration of antineoplastic
      therapy, and the agents, both commercially available and investigational, used to
      treat malignant diseases. Questions or suggestions for topics should be addressed
      to Dominic A. Solimando, Jr., President, Oncology Pharmacy Services, Inc., 4201
      Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J.
      Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology
      Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander
      Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

PMID- 27698501
TI  - Increasing Access to Naloxone and Legal Issues.

PMID- 27698502
TI  - Leadership Book Club: An Innovative Strategy to Incorporate Leadership
      Development Into Pharmacy Residency Programs.
AB  - Purpose: To describe an innovative strategy for incorporating leadership training
      and development across multiple postgraduate year 2 (PGY2) pharmacy residency
      programs at a single institution. Background: Tampa General Hospital has 7
      pharmacy residency positions: 4 postgraduate year 1 (PGY1) residents and a single
      resident for each of the 3 PGY2 programs (critical care, emergency medicine, and
      solid organ transplant). Administrative topics are incorporated across the PGY1
      and PGY2 residency programs, with each PGY2 program having additional
      administrative topics specific to their specialty area. Summary: What began as an
      elective administrative topic discussion for the PGY2 emergency medicine resident
      has evolved over time into a longitudinal leadership book club. The leadership
      book club is utilized to meet the residency goals and objectives related to
      leadership development for all 3 PGY2 programs. Each year a single book is
      identified through the American Society of Health-System Pharmacists (ASHP)
      Leadership Academy book list or by participant suggestion. The book is then
      divided into 4 sections with corresponding hour-long discussions that occur
      quarterly throughout the residency year. The residency program directors (RPDs)
      and co-RPDs lead the initial discussion, and each PGY2 resident leads 1 of the
      subsequent 3 discussions. Based on resident feedback, the leadership book club is
      an innovative and effective strategy to incorporate leadership training and
      development into residency training. Conclusion: It is imperative to foster the
      development of leadership skills in pharmacy residency programs to prevent a
      future leadership gap in health system pharmacy. Leadership book club is a unique
      strategy to incorporate leadership training longitudinally across multiple PGY2
      residency programs at a single institution.

PMID- 27698503
TI  - Impact of a Pharmacy-Led Pain Management Team on Adults in an Academic Medical
      Center.
AB  - Background: Pain is a major health problem affecting more than 15% of adults in
      the United States. In a multidisciplinary pain management team, pharmacists can
      optimize pharmacotherapy quality by ensuring safe and appropriate medication use.
      Objective: Assess the impact of a pharmacy pain medication management service on
      pain-related outcomes in an adult inpatient population. Methods: This
      retrospective study evaluated patients who were admitted from November 2009
      through November 2011 and received a pharmacy pain consult. Patients were
      excluded if they left against medical advice, their care was assumed by
      palliative care, or they had no complaint of pain when seen by the pharmacist.
      The primary outcome was the difference between each patient's average pain score
      from pre-consult to post-consult. Secondary outcomes were difference between each
      patient's average pain score from pre-consult to pre-discharge, overall
      functional improvement, pharmacist interventions, and 14-day and 30-day
      readmissions. Results: One hundred patients were included in the final analysis.
      Eight hundred twenty-one interventions were made by the clinical pharmacists.
      Patients displayed a significant reduction in their pre- and post-consult pain
      intensity scores on a 0 to 10 numerical rating scale (6.15 vs 3.25; p < .001).
      Likewise, a significant reduction in pain intensity scores was seen from pre
      consult to pre-discharge (6.15 vs 3.6; p < .001). Overall functional improvement,
      specifically sleep, mobility, and appetite, was seen in 86.6% of patients.
      Conclusions: Pain management is an area that provides opportunities for
      pharmacotherapy interventions. Pharmacists' involvement in pain management on an
      inpatient consult service had a positive impact on pain scores and improvement in
      functionality.

PMID- 27698504
TI  - Impact of Medication Dose Tracking Technology on Nursing Practice.
AB  - Objective: The impact of providing nursing staff access to data collected through
      a medication dose tracking technology (MDTT) web portal was investigated.
      Methods: A quasi-experimental, nonrandomized, pre-post intervention study was
      conducted in the Cardiothoracic Intensive Care Unit (CTICU) at Duke University
      Hospital. The change in the number of medication requests per dispense routed to
      the pharmacy electronic health record (EHR) in-basket was analyzed pre and post
      web portal access. Other endpoints included the number of MDTT web portal queries
      per day by nursing staff, change in nursing satisfaction survey scores, and
      technician time associated with processing medication requests pre and post web
      portal access. The pre web portal access phase of the study occurred from June 1,
      2014 to August 31, 2014. The post web portal access phase occurred from October
      1, 2014 to December 31, 2014. Results: An 11.4% decrease in the number of
      medication requests per dispense was exhibited between the pre and post web
      portal access phases of the study (0.0579 vs 0.0513, respectively; p < .001). Pre
      and post surveys showed a significant improvement in nurses' satisfaction
      regarding access to information on the location of medications (p = .009).
      Additionally, CTICU nursing staff utilized the MDTT web portal for 3.21 queries
      per day from October 1, 2014 to December 31, 2014. Conclusion: Providing nurses
      access to data collected via an MDTT decreased the number of communications
      between nursing and pharmacy staff regarding medication availability and led to
      statistically significant improvements in nursing satisfaction for certain
      aspects of the medication distribution process.

PMID- 27698505
TI  - Guidelines for the Establishment of Appropriate Beyond Use Dating of Sterile
      Compounded Admixtures.
AB  - To support compounding of products that are sterile and chemically stable, beyond
      use dating of admixtures must include a thorough evaluation of appropriate
      resources. In most instances, resources provide documentation of a specific
      compounded admixture, at a specific concentration and storage parameters, that
      does not coincide with current operations or patient-specific requirements. To
      meet the operational demands of a pharmacy, institutions employ a referenced
      guideline approach to guide decision making for safe sterile admixing. Often
      these guidelines are established and maintained at individual practicing
      locations with varying levels of detail and accuracy. In an effort to improve
      sterile compounding across a multihospital system, we developed and implemented
      beyond use dating guidelines to improve consistency and patient safety while
      meeting regulatory concerns.

PMID- 27698506
TI  - Comparison of Time to Therapeutic aPTT in Patients Who Received Continuous
      Unfractionated Heparin After Implementation of Pharmacy-wide Intervention Alerts.
AB  - Background: For patients on continuous IV unfractionated heparin (UFH), failing
      to achieve a therapeutic aPTT by 24 hours can be associated with increased
      morbidity. A pharmacy clinical surveillance system (PCSS) subtherapeutic aPTT
      alert was implemented at our institution to improve achievement of therapeutic
      aPTT goals by 24 hours. Objective: The primary objective was the time to achieve
      the minimum goal aPTT before and after the alert implementation. The secondary
      objectives were to examine the percentage of patients who achieved the minimum
      goal aPTT by 24 hours and the number of dose changes to achieve the minimum goal
      aPTT. Methods: A single-center retrospective study was conducted to include all
      adult inpatients receiving a continuous UFH infusion during a 3-month period
      prior to the implementation of a subtherapeutic aPTT alert and a 3-month period
      after implementation. Results: 317 patients were included in the analysis. The
      average time to achieve the minimum goal aPTT was 21.8 hours prior to alert
      implementation and 15.4 hours after implementation (p = .002). The percent of
      patients who achieved the minimum goal aPTT by 24 hours was 65.7% prior to alert
      implementation and 82.4% after implementation (p = .035). The average number of
      dose changes necessary to achieve aPTT value to the minimum goal aPTT prior to
      alert implementation was 1.67 and 1. 98 after implementation (p = .68).
      Conclusion: This analysis showed that implementation of a PCSS subtherapeutic
      aPTT alert for patients on continuous UFH infusions may ensure patients reach
      goal aPTT faster and facilitate a higher percent of patients who achieve the
      minimum goal aPTT by 24 hours.

PMID- 27698507
TI  - Case Study of Fatal Stroke Following Intranasal Lidocaine.
AB  - A 39-year-old man presented with new onset right hemiparesis and aphasia within
      an hour of using approximately 120 mL lidocaine 4% topical solution intranasally.
      Lidocaine had been prescribed over a 3-week period for pain due to multiple
      debridements of the nasal septum. A total of 650 mL of 4% lidocaine (26 g) had
      been dispensed to the patient during this time. The patient had a significant
      history of drug abuse, including snorting crushed tablets. Otherwise he was a
      healthy man with no chronic diseases or conditions. On arrival, and from previous
      exams, EKGs were normal without conduction delays. Electrolytes and CBC results
      were within normal range. The MRI/MRA showed a new thrombus with left middle
      cerebral artery distribution affecting one-third of the brain mass, including
      brain stem. Lidocaine likely contributed to cardiovascular embolic development,
      possibly from a sudden drop in blood pressure and known cardiovascular effects of
      sodium channel blockade. The patient expired from acute respiratory failure
      secondary to brainstem damage. Solutions of topical lidocaine should not be
      prescribed for use on open wounds or abraded skin as drug absorption will be
      increased, especially in highly vascularized nasal passages.

PMID- 27698509
TI  - Approvals, Submission, and Important Labeling Changes for US Marketed
      Pharmaceuticals.
AB  - This monthly feature will help readers keep current on new drug, new indications,
      dosage forms and safety-related changes in labeling or use. Efforts have been
      made to assure the accuracy of this information; however, if there are any
      questions, please let us know at jgeneral@ku.edu.

PMID- 27698508
TI  - Elbasvir/Grazoprevir.
AB  - Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well
      documented monographs on drugs that are newly released or are in late phase 3
      trials. The monographs are targeted to Pharmacy & Therapeutics Committees.
      Subscribers also receive monthly 1-page summary monographs on agents that are
      useful for agendas and pharmacy/nursing in-services. A comprehensive target drug
      utilization evaluation/medication use evaluation (DUE/MUE) is also provided each
      month. With a subscription, the monographs are available online to subscribers.
      Monographs can be customized to meet the needs of a facility. Through the
      cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in
      this column. For more information about The Formulary Monograph Service, contact
      Wolters Kluwer customer service at 866-397-3433. The September 2016 monograph
      topics are barictinib, buprenorphine implants, sarilumab, sofosbuvir/velpatasvir,
      and cholera vaccine, live, oral. The Safey MUE is on sofosbuvir/velpatasvir.

PMID- 27698510
TI  - Summaries of Safety Labeling Changes Approved by the FDA: Boxed Warnings
      Highlights.
AB  - As part of the US Food and Drug Administration's MedWatch program, safety
      labeling changes are reviewed and compiled monthly for drugs and therapeutic
      biologics where important changes have been made to the safety information. Boxed
      warnings
      (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guida
      ces/ucm075096.pdf) are ordinarily used to highlight either adverse reactions so
      serious in proportion to the potential benefit from the drug that it is essential
      that it be considered in assessing the risks and benefits of using the drugs or
      serious adverse reactions that can be prevented/reduced in frequency or severity
      by appropriate use of the drug; or FDA approved the drug with restrictions to
      ensure safe use because FDA concluded that the drug can be safely used only if
      distribution or use is restricted. There were 10 revised boxed warnings and 1
      drug class change from April through June 2016.

PMID- 27698511
TI  - Consider Adopting Collaborative Project Management Software.
AB  - Pharmacy administrators are often tasked with a range of responsibilities, from
      strategic planning and human resources to information systems management. Because
      of this, tools to support administrators' efficient and appropriate attention to
      everything on their plate can be valuable. Identification and evaluation of the
      available tools should be guided by careful consideration of the department's
      needs.

PMID- 27698512
TI  - Precautionary Savings in Mexico: Evidence from the Mexican Health and Aging
      Study.
AB  - Precautionary saving is the additional saving done by individuals to protect them
      financially in situations of uncertainty and reduce their vulnerability for
      negative shocks that may affect their consumption levels. This paper investigates
      the existence and extent of savings motivated by precaution in Mexico for people
      aged between 50 and 75, using data from the Mexican Health and Ageing Study 2003.
      The empirical strategy is based on a test of the direct relationship between the
      accumulated wealth and the uncertainty generated by the social security status,
      in particular the availability of health insurance, accounting also for the
      expectation to receive a retirement pension. The endogeneity-corrected estimates
      do not yield results that unequivocally support the existence of private savings
      as a risk protection mechanism, implying that the public protection system has an
      important role in reducing the vulnerability of the population studied.

PMID- 27698513
TI  - On the origin of carbon dioxide released from rewetted soils.
AB  - When dry soils are rewetted a pulse of CO2 is invariably released, and whilst
      this phenomenon has been studied for decades, the precise origins of this CO2
      remain obscure. We postulate that it could be of chemical (i.e. via abiotic
      pathways), biochemical (via free enzymes) or biological (via intact cells)
      origin. To elucidate the relative contributions of the pathways, dry soils were
      either sterilised (double autoclaving) or treated with solutions of inhibitors
      (15% trichloroacetic acid or 1% silver nitrate) targeting the different modes.
      The rapidity of CO2 release from the soils after the drying:rewetting (DRW) cycle
      was remarkable, with maximal rates of evolution within 6 min, and 41% of the
      total efflux over 96 h released within the first 24 h. The complete cessation of
      CO2 eflux following sterilisation showed there was no abiotic (dissolution of
      carbonates) contribution to the CO2 release on rewetting, and clear evidence for
      an organismal or biochemical basis to the flush. Rehydration in the presence of
      inhibitors indicated that there were approximately equal contributions from
      biochemical (outside membranes) and organismal (inside membranes) sources within
      the first 24 h after rewetting. This suggests that some of the flux was derived
      from microbial respiration, whilst the remainder was a consequence of enzyme
      activity, possibly through remnant respiratory pathways in the debris of dead
      cells.

PMID- 27698514
TI  - Synthesis of Psoralidin derivatives and their anticancer activity: First
      synthesis of Lespeflorin I1.
AB  - Synthetic scheme for the preparation of a number of different derivatives of
      anticancer natural product Psoralidin is described. A convergent synthetic
      approach is followed using simple starting materials like substituted phenyl
      acetic esters and benzoic acids. The developed synthetic route leads us to
      complete the first synthesis of an analogous natural product Lespeflorin I1, a
      mild melanin synthesis inhibitor. Preliminary bioactivity studies of the
      synthesized compounds are carried out against two commonly used prostate cancer
      cell lines. Results show that the bioactivity of the compounds can be manipulated
      by the simple modification of the functional groups.

PMID- 27698515
TI  - Clinical Reasoning: The Analysis of Medical Decision Making.

PMID- 27698516
TI  - Helping create "Wellness Warriors": Primary Care for remote Alaska Native
      Communities.

PMID- 27698517
TI  - Mortality Among Children And Young People Who Survive Cancer In Northern Ireland.
AB  - ABSTRACT: Whilst survival rates for childhood cancers are excellent, it is known
      that these patients have an increased risk of death from disease recurrence and
      other causes. We investigate patterns, trends and survival of cancers in children
      and young adults in N. Ireland. MATERIALS AND METHODS: 21 years (1993-2013) of
      cancer incidence data including non-malignant brain tumours from the N. Ireland
      Cancer Registry for persons aged 0-24 years was analysed using Joinpoint
      regresssion for trend and the Kaplan Meier method for survival analysis up to end
      2013 with excess mortality calculated at one and five years after first cancer
      diagnosis using standardised mortality ratios. RESULTS: 2633 children and young
      people were diagnosed with cancer, 1386 (52.6%) male and 1247 female with 1139
      (43.3%) aged 0-14. While trends increased over time they did not reach
      statistical significance except in the 15-24 age group for males and females
      combined. The most common cancers for age 0-14 were brain, eye and central
      nervous system and leukaemia with skin (including non-melanoma skin) the most
      common in the 15-24 age group. 59 patients (2.2%) had a record of a second
      cancer. Survival was high at 90.7% after 1 year, better among females and similar
      for older and younger groups. Although mortality in children is low overall,
      there was an excess mortality 24.7% (22-27.5) p<0.001 at one year and 7.3% (5.5
      9.2) p<0.001 for those who survived 5 years. Excluding the primary cancer there
      was an excess mortality for one year survivors, with deaths twice that of the
      background level (SMR= 2.2 (1.3-3.0)p=0.005 and although one and a half times
      background levels at 5 years, the excess mortality was not significant 1.5 (0.6
      2.3 p=0.269). CONCLUSION: Whilst survival from childhood cancers is excellent,
      this work in common with larger studies, highlights the need for ongoing
      monitoring of cancer survivors. Preventable skin cancer was identified as a
      problem in young adults.

PMID- 27698518
TI  - Pruritus: an overview. What drives people to scratch an itch?
AB  - Pruritus is a common complaint associated with many conditions. It negatively
      impacts sleep, quality of life, and mortality. Itch is transmitted along both
      histaminergic and non-histaminergic pathways with a complex interplay between
      keratinocytes, immune cells and cutaneous neurons. Individuals who present with
      pruritus should undergo a thorough assessment, especially those over 65 years
      old, to exclude underlying malignancy. Treatment no longer consists of
      antihistamines alone. Physicians now have an array of therapies in their
      armamentarium, to help alleviate this distressing symptom.

PMID- 27698519
TI  - Uterotonics for Non-emergent Caesarean Section: Protocol Change During UK
      Licensed Drug Shortage.
AB  - The aim was to assess the efficacy of Syntometrine (r) (500 micrograms
      ergometrine with 5 units oxytocin) as an appropriate alternative first-line
      uterotonic for use in elective caesarean section (CS) during a national shortage
      of UK-licensed IV oxytocin from April-June 2014. An observational study was
      performed involving 2 groups of 22 women undergoing elective CS in a UK DGH
      during this period. Primary endpoints included mean estimated blood loss (EBL),
      haemoglobin drop post-operatively and transfusion requirement. Secondary
      endpoints were use of antiemetics and mean post-operative nausea and vomiting
      (PONV) score. Results for Syntometrine (r) groups and syntocinon groups
      respectively: mean EBL (ml) 527.3 vs. 550.0 (p=0.5820), mean haemoglobin drop
      (g/dL) 0.977 vs. 0.982 (p=0.98), blood transfusion 1/22 vs. 0/22 (p=1). Intra
      operative antiemetics 20/22 vs. 6/22 (p=<0.001), post-operative antiemetics 2/22
      vs. 2/22 (p=1), mean PONV score 11.5 vs. 3.5 (p=0.099). As no significant
      difference in primary endpoints or PONV scores was observed between regimes, we
      conclude Syntometrine (r) was a safe first-line haemostatic agent for elective CS
      during oxytocin shortage.

PMID- 27698521
TI  - Electroconvulsive Therapy - What Do Patients Think Of Their Treatment?
AB  - BACKGROUND: The Regulation and Quality Improvement Authority (RQIA) monitors the
      administration of electroconvulsive therapy (ECT) in Northern Ireland (NI). As
      part of their inspection methodology RQIA wished to include feedback from ECT
      patients. The aim of this report is to summarise the opinions of ECT patients
      over a 1-year period and to compare their feedback about treatment with the
      standards of best practice, as defined by the Electroconvulsive Therapy
      Accreditation Service (ECTAS). METHOD: RQIA was granted permission to use the
      ECTAS patient questionnaire. The questionnaire was distributed to all the ECT
      clinics in NI and staff were requested to give them to patients who had received
      a course of ECT. RESULTS: A total of 42 individuals returned questionnaires, 24
      females (57.1%) and 18 (42.9%) males. The response rate was 26%. Almost half of
      respondents were detained under the Mental Health (Northern Ireland) Order 1986
      (n=19, 45.2%), with one third receiving ECT as a day patient (n=14, 33.3%).
      Respondents reported having detailed information about ECT, with ECTAS standards
      4.2 and 4.3 being affirmed in over 80% of cases. Eighty percent of respondents
      (n=34) believed they benefited from ECT. CONCLUSION: The results are mainly
      favourable towards ECT. The majority felt they benefited from treatment.

PMID- 27698520
TI  - Re-Staging Following Long-Course Chemoradiotherapy For Rectal Cancer: Does It
      Influence Management?
AB  - BACKGROUND: In patients with locally advanced or low rectal cancers, long-course
      chemoradiotherapy (LCCRT) is recommended prior to surgical management.1 The need
      for restaging afterwards has been questioned as it may be difficult to interpret
      imaging due to local tissue effects of chemoradiotherapy. The purpose of this
      study was to determine if restaging affected the management of patients receiving
      long-course chemoradiotherapy for rectal cancer. METHODS: A retrospective review
      of patients with rectal cancer discussed at the South Eastern Health and Social
      Care Trust Lower Gastrointestinal Multi-Disciplinary Team Meeting (LGIMDT) in
      2013 who had received long-course chemoradiotherapy was performed. Patients were
      identified from the Trust Audit Department, LGIMDT notes and patient records.
      Imaging results and outcomes from meetings were obtained through the Northern
      Ireland Picture Archiving and Communications System(r) (NIPACS) and Electronic
      Care Record(r) (ECR). Data including patient demographics, initial radiological
      staging and LGIMDT discussion, restaging modality and result, outcome from post
      treatment LGIMDT discussion and recorded changes in management plans were
      documented using a proforma. RESULTS: Seventy-one patients with rectal cancer
      were identified as having LCCRT in 2013 (M:F 36:35; age range 31 - 85 years).
      Fifty-nine patients were restaged following long-course treatment with computed
      tomography (CT) and magnetic resonance imaging (MRI). Twelve patients did not
      undergo restaging. Data was not available for 6 patients, one patient underwent
      emergency surgery, two patients were not fit for treatment, one failed to attend
      for restaging and two patients died prior to completion of treatment. Of the 59
      patients restaged, 19 patients (32%) had their management plan altered from that
      which had been proposed at the initial LGIMDT discussion. The most common change
      in plan was not to operate. Ten patients had a complete clinical and radiological
      response to treatment and have undergone intensive follow-up. Nine patients had
      disease progression, with 3 requiring palliative surgery and 6 referred for
      palliative care. CONCLUSION: Of those patients who were restaged, 32% had their
      management plan altered from that recorded at the initial LGIMDT discussion.
      Seventeen per cent of patients in this group had a complete clinical and
      radiological response to treatment. Fifteen percent demonstrated disease
      progression. We recommend, therefore, that patients with rectal cancer be
      restaged with CT and MRI following long-course chemoradiotherapy as surgery may
      be avoided in up to 27% of cases.

PMID- 27698522
TI  - Systemic Therapy In Acquired Haemophilia - A Single Institute Experience.
AB  - A cornerstone of the management of Acquired Haemophilia A (AHA) involves
      inhibitor eradication. First line immunosuppressive agents are usually steroids,
      either alone or in combination with cyclophosphamide. We present the use of
      Rituximab, cyclophosphamide, vincristine and prednisolone (RCVP) combination as
      immunosuppressant in AHA in a small cohort of patients in order to control their
      symptoms and eradicate inhibitors. This was a retrospective analysis of all AHA
      patients treated at the Northern Ireland Haemophilia centre over a six year
      period. During this time, a total of six patients were newly diagnosed with AHA.
      Four of these patients failed to respond conventional therapy of steroids and
      cyclophosphamide, they were however successfully treated with RCVP/ RCV. All
      patients achieved complete remission with this regimen after 1 to 2 cycles of
      treatment. Remission has been maintained for an extended time period (range 33-69
      months). As AHA is related to immune modulation and, in some cases, underlying
      malignancy we decided to use this regime as it is effective in either condition.
      From our experience, we demonstrate that RCVP combination is a promising
      treatment in patients with AHA who fail to respond to steroids alone or who have
      been on pre-existing immunosuppression.

PMID- 27698523
TI  - Radial Multi-Site, Longitudinal Multi-Polar Epicardial Left Ventricular Pacing In
      Tricuspid Valve Disease.

PMID- 27698524
TI  - Orthopaedic Surgery in World War II: Military and Medical Role of Northern
      Ireland.

PMID- 27698525
TI  - Letters.

PMID- 27698526
TI  - Curiositas (Dermatology).

PMID- 27698527
TI  - Game changers.

PMID- 27698528
TI  - So You want to be an Emergency Physician?

PMID- 27698530
TI  - Wage Growth, Landholding, and Mechanization in Chinese Agriculture.
AB  - This paper aims to examine the dynamics of land transactions, machine
      investments, and the demand for machine services using farm panel data from
      China. Recently, China's agriculture has experienced a large expansion of machine
      rentals and machine services provided by specialized agents, which has
      contributed to mechanization of agricultural production. On the other hand, the
      empirical results show that an increase in non-agricultural wage rates leads to
      expansion of self-cultivated land size. A rise in the proportion of non
      agricultural income or the migration rate also increases the size of self
      cultivated land. Interestingly, however, relatively educated farm households
      decrease the size of self-cultivated land, which suggests that relatively less
      educated farmers tend to specialize in farming. The demand for machine services
      has also increased if agricultural wage and migration rate increased over time,
      especially among relatively large farms. The results on crop income also support
      complementarities between rented-in land and machine services (demanded), which
      implies that scale economies are arising in Chinese agriculture with
      mechanization and active land rental markets.

PMID- 27698529
TI  - Theory-based metrological traceability in education: A reading measurement
      network.
AB  - Huge resources are invested in metrology and standards in the natural sciences,
      engineering, and across a wide range of commercial technologies. Significant
      positive returns of human, social, environmental, and economic value on these
      investments have been sustained for decades. Proven methods for calibrating test
      and survey instruments in linear units are readily available, as are data- and
      theory-based methods for equating those instruments to a shared unit. Using these
      methods, metrological traceability is obtained in a variety of commercially
      available elementary and secondary English and Spanish language reading education
      programs in the U.S., Canada, Mexico, and Australia. Given established historical
      patterns, widespread routine reproduction of predicted text-based and
      instructional effects expressed in a common language and shared frame of
      reference may lead to significant developments in theory and practice.
      Opportunities for systematic implementations of teacher-driven lean thinking and
      continuous quality improvement methods may be of particular interest and value.

PMID- 27698531
TI  - Shoot traits and their relevance in terminal drought tolerance of chickpea (Cicer
      arietinum L.).
AB  - Chickpea is the second most important legume crop largely grown under semi-arid
      tropics where terminal drought is one of the major constraints for its
      productivity. A trait-based selection had been considered more beneficial in
      drought tolerance breeding to overcome the environmental influence on drought
      yields. Large number of traits had been suggested in literature, with less
      indication on their importance and priority, for use in such breeding programs
      resulting in poor utilization of critical traits in drought tolerance breeding.
      To identify the most critical traits that contribute to grain yield under
      drought, 12 chickpea genotypes, with well-defined drought response, were field
      evaluated by sampling at regular intervals during the cropping period. Large
      range of variation was observed for shoot biomass productivity, specific leaf
      area (SLA) and leaf area index (LAI) at different days after sowings (DAS),
      canopy temperature depression (CTD) at mid-reproductive stages, growth duration
      and both morphological and analytical yield components. Grain yield under drought
      was closely associated with the rate of partitioning (p), crop growth rate (C),
      CTD, phenology, LAI at mid-pod fill stage, pod number m-2 at maturity, shoot
      biomass at reproductive growth stages and SLA at physiological maturity. The
      shoot trait(s) were prioritized based on their significance and contribution to
      drought tolerance. The trait(s) that conferred tolerance varied across genotypes.
      The order of traits/plant functions identified as important and critical for the
      drought tolerance were p, C, CTD, growth duration and other related traits.
      Relatively less important traits were LAI, SLA at the mid reproductive stage and
      pod number per unit area at maturity. The traits Dr, seeds pod-1 and 100-seed
      weight were found to be least important. Breeding for the best combination of p
      and C with the right phenology was proposed to be the best selection strategy to
      enhance terminal drought tolerance in chickpea.

PMID- 27698532
TI  - Evaluation of the effects of mulch on optimum sowing date and irrigation
      management of zero till wheat in central Punjab, India using APSIM.
AB  - Machinery for sowing wheat directly into rice residues has become more common in
      the rice-wheat systems of the north-west Indo-Gangetic Plains of South Asia, with
      increasing numbers of farmers now potentially able to access the benefits of
      residue retention. However, surface residue retention affects soil water and
      temperature dynamics, thus the optimum sowing date and irrigation management for
      a mulched crop may vary from those of a traditional non-mulched crop.
      Furthermore, the effects of sowing date and irrigation management are likely to
      vary with soil type and seasonal conditions. Therefore, a simulation study was
      conducted using the APSIM model and 40 years of weather data to evaluate the
      effects of mulch, sowing date and irrigation management and their interactions on
      wheat grain yield, irrigation requirement (I) and water productivity with respect
      to irrigation (WPI) and evapotranspiration (WPET). The results suggest that the
      optimum wheat sowing date in central Punjab depends on both soil type and the
      presence or absence of mulch. On the sandy loam, with irrigation scheduled at 50%
      soil water deficit (SWD), the optimum sowing date was late October to early
      November for maximising yield, WPI and WPET. On the clay loam, the optimum date
      was about one week later. The effect of mulch on yield varied with seasonal
      conditions and sowing date. With irrigation at 50% SWD, mulching of wheat sown at
      the optimum time increased average yield by up to 0.5 t ha-1. The beneficial
      effect of mulch on yield increased to averages of 1.2-1.3 t ha-1 as sowing was
      advanced to 15 October. With irrigation at 50% SWD and 7 November sowing, mulch
      reduced the number of irrigations by one in almost 50% of years, a reduction of
      about 50 mm on the sandy loam and 60 mm on the clay loam. The reduction in
      irrigation amount was mainly due to reduced soil evaporation. Mulch reduced
      irrigation requirement by more as sowing was delayed, more so on the sandy loam
      than the clay loam soil. There was little effect of mulch on irrigation
      requirement for late October sowings. There were large trade-offs between
      irrigation input, yield, WPET and WPI on the sandy loam with regard to the
      optimum irrigation schedule. Maximum yield occurred with very frequent irrigation
      (10-20% SWD) which also had the greatest irrigation input, while WPI was highest
      with least frequent irrigation (70% SWD), and WPET was highest with irrigation at
      40-50% SWD. This was the case with and without mulch. On the clay loam, the trade
      offs were not so pronounced, as maximum yield was reached with irrigation at 50%
      SWD, with and without mulch. However, both WPET and WPI were maximum and
      irrigation input least at the lowest irrigation frequency (70% SWD). On both
      soils, maximum yield, WPET and WPI were higher with mulch, while irrigation input
      was slightly lower, but mulch had very little effect on the irrigation thresholds
      at which each parameter was maximised.

PMID- 27698533
TI  - Astaxanthin affects oxidative stress and hyposalivation in aging mice.
AB  - Oral dryness, a serious problem for the aging Japanese society, is induced by
      aging-related hyposalivation and causes dysphagia, dysgeusia, inadaptation of
      dentures, and growth of oral Candida albicans. Oxidative stress clearly plays a
      role in decreasing saliva secretion and treatment with antioxidants such
      astaxanthin supplements may be beneficial. Therefore, we evaluated the effects of
      astaxanthin on the oral saliva secretory function of aging mice. The saliva flow
      increased in astaxanthin-treated mice 72 weeks after administration while that of
      the control decreased by half. The plasma d-ROMs values of the control but not
      astaxanthin-treated group measured before and 72 weeks after treatment increased.
      The diacron-reactive oxygen metabolites (d-ROMs) value of astaxanthin-treated
      mice 72 weeks after treatment was significantly lower than that of the control
      group was. The plasma biological antioxidative potential (BAP) values of the
      control but not astaxanthin-treated mice before and 72 weeks after treatment
      decreased. Moreover, the BAP value of the astaxanthin-treated group 72 weeks
      after treatment was significantly higher than that of the control was.
      Furthermore, the submandibular glands of astaxanthin-treated mice had fewer
      inflammatory cells than the control did. Specifically, immunofluorescence
      revealed a significantly large aquaporin-5 positive cells in astaxanthin-treated
      mice. Our results suggest that astaxanthin treatment may prevent age-related
      decreased saliva secretion.

PMID- 27698534
TI  - Raf kinase inhibitor protein regulates oxygen-glucose deprivation-induced PC12
      cells apoptosis through the NF-kappaB and ERK pathways.
AB  - Raf-1 kinase inhibitory protein (RKIP) is a critical molecule for cellular
      responses to stimuli. In this study, we investigated whether RKIP is responsible
      for neural cell apoptosis induced by oxygen-glucose deprivation (OGD) and
      explored the role of NF-kappaB and ERK pathways regulated by RKIP under OGD
      stimuli. RKIP was overexpressed or knocked down using lentivirus in PC12 cells,
      which were then challenged by OGD. RKIP overexpression significantly increased
      the cell viability of OGD cells, and attenuated apoptosis, cell cycle arrest, and
      reactive oxygen species generation. RKIP knockdown induced reverse effects.
      Moreover, we found that RKIP interacted with TAK1, NIK, IKK, and Raf-1 and
      negatively regulated the NF-kappaB and ERK pathways. RKIP overexpression
      significantly inhibited IKK, IkappaBalpha, and P65 phosphorylation in NF-kappaB
      pathway and MEK, ERK, and CREB phosphorylation in ERK pathway, respectively. RKIP
      knockdown induced reverse effects. Furthermore, a NF-kappaB inhibitor BAY 11-7082
      and a MEK inhibitor U0126 blocked the changes caused by RKIP down-regulation
      after OGD. In conclusion, these results demonstrate that RKIP plays a key role in
      neural cell apoptosis caused by OGD partly via regulating NF-kappaB and ERK
      pathways. The present study may provide new insights into the role of RKIP in
      ischemic stroke.

PMID- 27698535
TI  - l-Theanine protects against excess dopamine-induced neurotoxicity in the presence
      of astrocytes.
AB  - l-Theanine (gamma-glutamylethylamide), a component of green tea, is considered to
      have regulatory and neuroprotective roles in the brain. The present study was
      designed to determine the effect of l-theanine on excess dopamine-induced
      neurotoxicity in both cell culture and animal experiments. The primary cultured
      mesencephalic neurons or co-cultures of mesencephalic neurons and striatal
      astrocytes were pretreated with l-theanine for 72 h, and then treated with excess
      dopamine for further 24 h. The cell viability of dopamine neurons and levels of
      glutathione were evaluated. Excess dopamine-induced neurotoxicity was
      significantly attenuated by 72 h preincubation with l-theanine in neuron
      astrocyte co-cultures but not in neuron-rich cultures. Exposure to l-theanine
      increased the levels of glutathione in both astrocytes and glial conditioned
      medium. The glial conditioned medium from l-theanine-pretreated striatal
      astrocytes attenuated dopamine-induced neurotoxicity and quinoprotein formation
      in mesencephalic neurons. In addition, replacement of l-glutamate with l-theanine
      in an in vitro cell-free glutathione-synthesis system produced glutathione-like
      thiol compounds. Furthermore, l-theanine administration (4 mg/kg, p.o.) for 14
      days significantly increased glutathione levels in the striatum of mice. The
      results suggest that l-theanine provides neuroprotection against oxidative stress
      induced neuronal damage by humoral molecules released from astrocytes, probably
      including glutathione.

PMID- 27698536
TI  - Synergistic antioxidative effect of astaxanthin and tocotrienol by co
      encapsulated in liposomes.
AB  - Astaxanthin and vitamin E are both effective antioxidants that are frequently
      used in cosmetics, as food additives, and in to prevent oxidative damage. A
      combination of astaxanthin and vitamin E would be expected to show an additive
      anntioxidative effect. In this study, liposomes co-encapsulating astaxanthin and
      the vitamin E derivatives alpha-tocopherol (alpha-T) or tocotrienols (T3) were
      prepared, and the antioxidative activity of these liposomes toward singlet oxygen
      and hydroxyl radical was evaluated in vitro. Liposomes co-encapsulating
      astaxanthin and alpha-T showed no additive anntioxidative effect, while the
      actual scavenging activity of liposomes co-encapsulating astaxanthin and T3 was
      higher than the calculated additive activity. To clarify why this synergistic
      effect occurs, the most stable structure of astaxanthin in the presence of alpha
      T or alpha-T3 was calculated. Only alpha-T3 was predicted to form hydrogen
      bonding with astaxanthin, and the astaxanthin polyene chain would partially
      interact with the alpha-T3 triene chain, which could explain why there was a
      synergistic effect between astaxanthin and T3 but not alpha-T. In conclusion, co
      encapsulation of astaxanthin and T3 induces synergistic scavenging activity by
      intermolecular interactions between the two antioxidants.

PMID- 27698537
TI  - Resveratrol improves salivary dysfunction in a non-obese diabetic (NOD) mouse
      model of Sjogren's syndrome.
AB  - Resveratrol is a natural polyphenol produced by plants in response to
      environmental stress. This compound has been shown to have pharmacological
      effects against a wide range of diseases including neurological, hepatic,
      cardiovascular and autoimmune conditions. The non-obese diabetic (NOD) mouse, in
      which loss of lacrimal and salivary gland function occurs, has been studied as an
      animal model for Sjogren's syndrome. In this study, we confirmed that
      administration of resveratrol results in increased secretion of saliva in NOD
      mice. Although resveratrol enhanced Sirt1 activity, inflammatory cell
      infiltration was not affected. Moreover, expression of the anti-inflammatory
      cytokine IL-10 in salivary glands was enhanced in the resveratrol-administered
      group. Thus, we confirmed a novel therapeutic effect for resveratrol on salivary
      dysfunction in Sjogren's syndrome.

PMID- 27698538
TI  - Vitamin A deficiency impacts the structural segregation of gut microbiota in
      children with persistent diarrhea.
AB  - To investigate whether gut microbiota is associated with vitamin A nutritional
      levels in children with persistent diarrhea, a total of 59 pediatric patients
      with persistent diarrhea aged 1-12 months were selected from the Department of
      Gastroenterology at the Children's Hospital of Chongqing Medical University,
      China. Subjects were hospitalized and divided into VA-deficient (n = 30) and VA
      normal (n = 29) groups according to their venous serum retinol levels. Fecal
      samples from all 59 subjects were collected immediately after admission and
      analyzed by Illumina MiSeq for 16S rRNA genes to characterize the overall
      microbiota of the samples. The gut microbiota of the VA-deficient and VA-normal
      groups were compared using a bioinformatic statistical approach. The Shannon
      index (p = 0.02), Simpson index (p = 0.01) and component diagram data indicated
      significantly lower diversity in the VA-deficient than the VA-normal group. A
      metagenome analysis (LEfSe) and a differentially abundant features approach using
      Metastats revealed that Escherichia coli and Clostridium butyricum were the key
      phylotypes of the VA-normal group, while Enterococcus predominated the VA
      deficient group. In conclusion, the diversity of gut microbiota and the key
      phylotypes are significantly different in children with persistent diarrhea at
      different VA nutritional levels.

PMID- 27698539
TI  - Energy metabolism and nutritional status in hospitalized patients with lung
      cancer.
AB  - This study aimed to investigate the energy metabolism of patients with lung
      cancer and the relationship between energy metabolism and proinflammatory
      cytokines. Twenty-eight patients with lung cancer and 18 healthy controls were
      enrolled in this study. The nutritional status upon admission was analyzed using
      nutritional screening tools and laboratory tests. The resting energy expenditure
      and respiratory quotient were measured using indirect calorimetry, and the
      predicted resting energy expenditure was calculated using the Harris-Benedict
      equation. Energy expenditure was increased in patients with advanced stage
      disease, and there were positive correlations between measured resting energy
      expenditure/body weight and interleukin-6 levels and between measured resting
      energy expenditure/predicted resting energy expenditure and interleukin-6 levels.
      There were significant relationships between body mass index and plasma leptin or
      acylated ghrelin levels. However, the level of appetite controlling hormones did
      not affect dietary intake. There was a negative correlation between plasma
      interleukin-6 levels and dietary intake, suggesting that interleukin-6 plays a
      role in reducing dietary intake. These results indicate that energy expenditure
      changes significantly with lung cancer stage and that plasma interleukin-6 levels
      affect energy metabolism and dietary intake. Thus, nutritional management that
      considers the changes in energy metabolism is important in patients with lung
      cancer.

PMID- 27698540
TI  - Influence of regular exercise on gastric emptying in healthy men: a pilot study.
AB  - Functional gastrointestinal disorders (FGIDs), including functional dyspepsia
      (FD), are common chronic disorders even in the younger population. Physical
      activity is advocated for patients with FGIDs, although the evidence is
      insufficient. We investigated the association between the intensity of regular
      exercise and gastric emptying to determine the effect of physical activity on
      dyspeptic symptoms. Thirty healthy individuals were selected and divided into
      three groups (low, moderate, and high) using the index of total exercise
      intensity in a week. Gastric emptying was evaluated by the 13C-acetate breath
      test. Gastroesophageal reflux symptoms, dyspeptic symptoms, stool forms, scores
      of anxiety and depression, and scores of sleep quality were also compared.
      Baseline scores of gastroesophageal reflux symptoms, anxiety, depression, and
      sleep quality were not different among the three groups. Gastric emptying was
      significantly faster in low-intensity exercise group than the moderate-intensity
      exercise group. Although the presence of loose stool and alcohol consumption were
      also associated with the intensity of regular exercise, these variables were not
      confounders. In conclusion, the intensity of regular exercise was independently
      associated with gastric emptying in healthy individuals. These baseline data
      would be useful for consideration of an optimal exercise intervention for the
      treatment of FD.

PMID- 27698541
TI  - Effects of isoflavones on lipid and apolipoprotein levels in patients with type 2
      diabetes in Heilongjiang Province in China.
AB  - In this study, we examined the association between soy isoflavones and lipid
      profiles, apolipoprotein levels in patients with type 2 diabetes in China. The
      study population was composed of 120 cases (80 women with type 2 diabetes and 40
      healthy women). Objects in treatment group received isoflavones 435 mg/day for 2
      months, then lipid profiles were analyzed by the colorimetry method and
      apolipoprotein levels were determined by immune turbidimetric method. And all the
      indexes were determined after oral glucose tolerance test. The levels of total
      cholesterol, triglyceride and LDL-C significantly reduced and the levels of HDL-C
      and apolipoprotein A1 significantly raised in the treatment group after
      intervention (p<0.05). After oral glucose tolerance test, the level of total
      cholesterol was lower at postprandial 6 h than at empty stomach in treatment
      group, it had significantly difference (p<0.05). LDL-C levels in the treatment
      group not only decreased after intervention, but also was significantly lower at
      postprandial 4, 6 h than in non-intervention group. The ratio of apolipoprotein
      A1/apolipoprotein B at postprandial 2 h was the highest after treatment in
      isoflavone group. Supplementation with 435 mg/day of isoflavones exerted
      favorable effect on the blood total cholesterol, LDL-C levels and the ratio of
      apolipoprotein A1/apolipoprotein B in Chinese type 2 diabetes women.

PMID- 27698542
TI  - Relationship between homeostasis model assessment of insulin resistance and beta
      cell function and serum 25-hydroxyvitamin D in non-diabetic Korean adults.
AB  - The purpose of this study is to look at these relationships in non-diabetic
      Korean adults. This study was based on data from the KNHANES V-1, which is
      representative of the population of Korea. A total of 5,492 participants (>=20
      years in age) without type 1 or type 2 diabetes, assessed for serum 25
      hydroxyvitamin D [25(OH)D], fasting blood glucose and insulin, as well as
      anthropometric variables, were included in the analyses. The key study results
      were as follows: First, vitamin D status [vitamin D deficient, 25(OH)D <25 nM;
      vitamin D insufficient, 25(OH)D >=25, <50 nM; vitamin D sufficient, 25(OH)D >=50
      nM] was inversely associated with homeostasis model assessment of insulin
      resistance (HOMA-IR) and beta cell function (HOMA-B) in model 2 (adjusted for age
      and gender) and 3 (further adjusted for smoking, alcohol drinking, regular
      exercise, systolic and diastolic blood pressure, waist circumference, and body
      mass index). Second, in model 4, when further adjusted for total cholesterol,
      triglycerides, and HDL-C, vitamin D status was inversely associated with HOMA-B.
      However, association of vitamin D status and HOMA-IR was no longer significant.
      In conclusion, vitamin D was inversely associated with beta cell function in non
      diabetic Korean adults but was not associated with insulin resistance.

PMID- 27698543
TI  - Analysis of negative result in serum anti-H. pylori IgG antibody test in cases
      with gastric mucosal atrophy.
AB  - The purpose is to elucidate factors related to negative results of anti-H. pylori
      antibody test in cases with gastric mucosal atrophy. A total of 859 individuals
      without past history of eradication therapy for H. pylori (545 males, 314
      females; mean age 52.4 years) who underwent an upper GI endoscopy examination and
      serological test were enrolled as subjects. Serological testing was performed
      using SphereLight H. pylori antibody J(r), and endoscopic findings of gastric
      mucosal atrophy by the classification of Kimura and Takemoto and post-eradication
      findings were analyzed. The positive rates for the anti-H. pylori antibody test
      in subjects with and without gastric mucosal atrophy were 85.6% and 0.9%,
      respectively. In analysis of subjects with gastric mucosal atrophy, a low
      positive rate and serum titer was observed in subjects with C1, C2 and O3
      atrophy. When the analysis was performed separately in male and female subjects,
      low positive rate was observed in males with O3 atrophy and females with C2
      atrophy. Suspected post-eradication endoscopic findings were more frequently
      observed in cases with C2 atrophy. In conclusion, negative result of anti-H.
      pylori antibody test was frequently observed in middle-aged subjects with C1, C2
      and O3 gastric mucosal atrophy.

PMID- 27698544
TI  - Esomeprazole- or rabeprazole-based triple therapy eradicated Helicobacter pylori
      comparably regardless of clarithromycin susceptibility and CYP2C19 genotypes.
AB  - The aim of this study was to assess the efficacy of esomeprazole-based triple
      therapy compared with rabeprazole-based triple therapy according to CYP2C19
      genotype and clarithromycin susceptibility status for first-line eradication
      therapy of Helicobacter pylori (H. pylori) in Japan. We enrolled 219 H. pylori
      infected patients, and randomly allocated patients to the EAC group (esomeprazole
      20 mg, clarithromycin 200 mg, amoxicillin 750 mg for one week, with all drugs
      given twice daily) or RAC group (rabeprazole 10 mg, clarithromycin 200 mg,
      amoxicillin 750 mg for one week, with all drugs given twice daily). The H. pylori
      eradication rate according to the PP analyses was 75.0% (95% CI: 65.2-82.8%) in
      the EAC group and 71.4% (95% CI: 61.4-79.1%) in the RAC group. There were no
      statistically significant differences. The eradication rates of the
      clarithromycin-resistant/-sensitive strains were, respectively, 45.0% (95% CI:
      30.7-60.2%)/98.0% (95% CI: 88.7-100%) in the EAC group and 39.5% (95% CI: 25.6
      55.3%)/93.5% (95% CI: 81.9-98.4%) in the RAC group. The eradication rate of the
      clarithromycin-sensitive strains was significantly higher than that of the
      resistant strains in both groups. In conclusion, EAC and RAC therapies show a
      comparable efficacy regardless of the CYP2C19 genotype and clarithromycin
      susceptibility status in Japan.

PMID- 27698546
TI  - Insights from lncRNAs Profiling of MIN6 Beta Cells Undergoing Inflammation.
AB  - Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease
      characterized by chronic and progressive apoptotic destruction of pancreatic beta
      cells. During the initial phases of T1DM, cytokines and other inflammatory
      mediators released by immune cells progressively infiltrate islet cells, induce
      alterations in gene expression, provoke functional impairment, and ultimately
      lead to apoptosis. Long noncoding RNAs (lncRNAs) are a new important class of
      pervasive genes that have a variety of biological functions and play key roles in
      many diseases. However, whether they have a function in cytokine-induced beta
      cell apoptosis is still uncertain. In this study, lncRNA microarray technology
      was used to identify the differently expressed lncRNAs and mRNAs in MIN6 cells
      exposed to proinflammatory cytokines. Four hundred forty-four upregulated and 279
      downregulated lncRNAs were detected with a set filter fold-change ?2.0. To
      elucidate the potential functions of these lncRNAs, Gene Ontology (GO) and
      pathway analyses were used to evaluate the potential functions of differentially
      expressed lncRNAs. Additionally, a lncRNA-mRNA coexpression network was
      constructed to predict the interactions between the most strikingly regulated
      lncRNAs and mRNAs. This study may be utilized as a background or reference
      resource for future functional studies on lncRNAs related to the diagnosis and
      development of new therapies for T1DM.

PMID- 27698545
TI  - Protective Effect of Galectin-1 during Histoplasma capsulatum Infection Is
      Associated with Prostaglandin E2 and Nitric Oxide Modulation.
AB  - Histoplasma capsulatum is a dimorphic fungus that develops a yeast-like
      morphology in host's tissue, responsible for the pulmonary disease
      histoplasmosis. The recent increase in the incidence of histoplasmosis in
      immunocompromised patients highlights the need of understanding immunological
      controls of fungal infections. Here, we describe our discovery of the role of
      endogenous galectin-1 (Gal-1) in the immune pathophysiology of experimental
      histoplasmosis. All infected wild-type (WT) mice survived while only 1/3 of
      Lgals1-/- mice genetically deficient in Gal-1 survived 30 days after infection.
      Although infected Lgals1-/- mice had increased proinflammatory cytokines, nitric
      oxide (NO), and elevations in neutrophil pulmonary infiltration, they presented
      higher fungal load in lungs and spleen. Infected lung and infected macrophages
      from Lgals1-/- mice exhibited elevated levels of prostaglandin E2 (PGE2, a
      prostanoid regulator of macrophage activation) and prostaglandin E synthase 2
      (Ptgs2) mRNA. Gal-1 did not bind to cell surface of yeast phase of H. capsulatum,
      in vitro, suggesting that Gal-1 contributed to phagocytes response to infection
      rather than directly killing the yeast. The data provides the first demonstration
      of endogenous Gal-1 in the protective immune response against H. capsulatum
      associated with NO and PGE2 as an important lipid mediator in the pathogenesis of
      histoplasmosis.

PMID- 27698547
TI  - Chronic hip dislocations: a rarity. How should we treat them?
AB  - BACKGROUND: Chronically dislocated hips (>6 weeks) are usually the consequence of
      difficulties accessing appropriate healthcare in a timely fashion after
      dislocation; this explains why they are more common in developing countries. Due
      to a lack of research, there is currently no consensus on the best treatment
      available for patients presenting with this condition. Therefore, it is important
      to assess the treatments available so as to ensure that doctors adequately manage
      those presenting with this debilitating condition in the future. OBJECTIVE: To
      identify the best treatment strategy for chronic hip dislocations based on the
      treatment outcomes achieved by a free surgical clinic in Phnom Penh, Cambodia.
      PATIENTS AND METHOD: A retrospective analysis of the surgical centre's electronic
      records was conducted. Patients presenting with hips dislocated for >6 weeks were
      included whilst congenitally dislocated hips were excluded. Treatment outcomes,
      based on follow up notes, were then assessed. Data abstracted during chart review
      was analysed using descriptive and comparative statistics. RESULTS: 72 patients
      presented to the clinic with chronic hip dislocations. 42 patients received
      recorded treatment and 32 were followed up. Among patients with follow-up, 63%
      experienced 'good' outcomes after treatment. Open reductions, the most common
      treatment, were successful 65% of the time. The use of preoperative traction
      increased the success of open reductions by 13%, however, this result was not
      statistically significant (p = 0.64). CONCLUSION: Open reductions with pre
      operative traction seem to be an acceptable treatment in this setting.

PMID- 27698549
TI  - Factors Associated with HIV Discussion and Condom Use with Sexual Partners in an
      Underserved Community in South Africa.
AB  - We examined factors associated with discussing HIV and condom use with a sexual
      partner. Two cross-sectional surveys were conducted in 2004 prior to the
      implementation of an HIV awareness campaign in a South African community and in
      2008 after a three-year education program. Overall, the proportion of individuals
      who had discussed HIV with a sexual partner increased from 76% in 2004 to 89% in
      2008 (p < .001). Among respondents who had sex six months before completing the
      surveys, condom use significantly increased from 64% in 2004 to 79% in 2008 (p <
      .05). Respondents who discussed HIV with a sexual partner were more likely to use
      condoms than respondents who had not discussed HIV with a sexual partner
      (OR=2.08, 95% CI=1.16, 3.72). These findings indicate the importance of
      interventions aimed at promoting HIV awareness and discussion of HIV in
      communities with individuals at risk of acquiring HIV.

PMID- 27698550
TI  - Intravitreal methotrexate infusion for proliferative vitreoretinopathy.
AB  - PURPOSE: The purpose of this study was to evaluate intravitreal methotrexate
      infusion (IMI) during pars plana vitrectomy (PPV) for retinal detachment in
      patients with high risk for the development of proliferative vitreoretinopathy
      (PVR). METHODS: Patients presenting with severe recurrent PVR with tractional
      retinal detachment and/or a history of severe ocular inflammation were treated
      with IMI. Clinical outcomes were determined from a retrospective medical chart
      review. RESULTS: Twenty-nine eyes presenting with either tractional retinal
      detachment and recurrent PVR (n=22) or a history of severe inflammation
      associated with high PVR risk (n=7) received IMI during PPV. Best-corrected
      visual acuity at 6 months was >=20/200 in 19 of 29 eyes (66%) and remained stable
      or improved compared with initial presentation in 24 of 29 eyes (83%). At the
      last follow-up examination, the retinas of 26 of 29 eyes (90%) remained attached
      after IMI while three eyes required another reattachment procedure. Three
      additional eyes (10%) developed recurrent limited PVR without recurrent RD and
      were observed. No complications attributable to IMI occurred during a mean follow
      up of 27 months. CONCLUSION: Eyes at high risk for PVR development due to a
      history of prior PVR or intraocular inflammation had a low incidence of PVR
      following IMI at the time of PPV for RD repair. No significant safety issues from
      IMI were observed in this series.

PMID- 27698551
TI  - Short wave-automated perimetry (SWAP) versus optical coherence tomography in
      early detection of glaucoma.
AB  - OBJECTIVE: To assess the role and diagnostic effectiveness of optical coherence
      tomography (OCT) and short wave-automated perimetry (SWAP) to distinguish between
      normal, glaucoma suspects, and surely diagnosed glaucomatous eye. BACKGROUND:
      Changes in the optic disc and retinal nerve fiber layer (RNFL) often precede the
      appearance of visual field defect with standard automated perimetry.
      Unfortunately, RNFL defect can be difficult to identify during clinical
      examination. Early detection of glaucoma is still controversial, whether by OCT,
      SWAP, or frequency-doubling technology perimetry. PATIENTS AND METHODS: In this
      randomized controlled, consecutive, prospective study, a total 70 subjects (140
      eyes) were included in the study, divided into three groups: Group A, 10 healthy
      volunteers (20 eyes); Group B, 30 patients (60 eyes) with glaucoma suspect; and
      Group C, 30 patients (60 eyes) with already diagnosed glaucomatous eyes. RESULTS:
      Average RNFL thickness was 75+/-9.0 in the glaucoma group, 99+/-15.5 in the
      control group, and 94+/-12 in glaucoma suspect. The inferior quadrant was the
      early parameter affected. There was significant correlation between visual field
      parameters and RNFL thickness in both glaucoma and glaucoma suspect groups.
      CONCLUSION: Both RNFL thickness measured by OCT and SWAP indices are good
      discrimination tools between glaucomatous, glaucoma suspect, and normal eyes. OCT
      parameters tend to be more sensitive than SWAP parameters.

PMID- 27698548
TI  - Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review.
AB  - Biodegradable magnesium (Mg) alloy stents are the most promising next generation
      of bio-absorbable stents. In this article, we summarized the progresses on the in
      vitro studies, animal testing and clinical trials of biodegradable Mg alloy
      stents in the past decades. These exciting findings led us to propose the
      importance of the concept "bio-adaption" between the Mg alloy stent and the local
      tissue microenvironment after implantation. The healing responses of stented
      blood vessel can be generally described in three overlapping phases:
      inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy
      stent, once implanted into the blood vessel, needs to be a reasonable function of
      the time and the space/dimension. First, a very slow degeneration of mechanical
      support is expected in the initial four months in order to provide sufficient
      mechanical support to the injured vessels. Although it is still arguable whether
      full mechanical support in stented lesions is mandatory during the first four
      months after implantation, it would certainly be a safety design parameter and a
      benchmark for regulatory evaluations based on the fact that there is insufficient
      human in vivo data available, especially the vessel wall mechanical properties
      during the healing/remodeling phase. Second, once the Mg alloy stent being
      degraded, the void space will be filled by the regenerated blood vessel tissues.
      The degradation of the Mg alloy stent should be 100% completed with no residues,
      and the degradation products (e.g., ions and hydrogen) will be helpful for the
      tissue reconstruction of the blood vessel. Toward this target, some future
      research perspectives are also discussed.

PMID- 27698552
TI  - Profile of adalimumab and its potential in the treatment of uveitis.
AB  - Uveitis refers to the presence of intraocular inflammation, and as a strict
      definition compromises the iris and ciliary body anteriorly and the choroid
      posteriorly (the uvea). Untreated, uveitis can lead to visual loss or blindness.
      The etiology of uveitis can include both infectious and noninfectious (usually
      immune-mediated) causes, the latter of which are often mediated predominantly by
      Th1 CD4+ T-cells that secrete proinflammatory cytokines. Tumor necrosis factor
      alpha (TNF-alpha) is a proinflammatory cytokine involved in the pathogenesis of
      uveitis, which at high concentrations can cause excess inflammation and tissue
      damage. Adalimumab is a recombinant human IgG1 monoclonal antibody specific for
      human TNF-alpha. Historically, corticosteroids and methotrexate were used to
      treat uveitis; however, newer biologic agents such as adalimumab have
      revolutionized therapy for noninfectious uveitis. Adalimumab has shown efficacy
      in treating refractory uveitis in multiple settings, including idiopathic
      disease, juvenile idiopathic arthritis, sarcoidosis, Behcets disease, and uveitis
      secondary to spondyloarthropathies, among several other noninfectious uveitis
      conditions. In this paper, we will review the profile of adalimumab, the role of
      TNF-alpha in uveitis, discuss safety data, and summarize key articles evaluating
      the efficacy of adalimumab in treating uveitis secondary to the most commonly
      associated autoimmune diseases.

PMID- 27698554
TI  - A qualitative investigation of barriers and facilitators of rehabilitation
      success from the psychosomatic inpatients' perspective.
AB  - OBJECTIVE: Psychosomatic inpatient rehabilitation aims at promoting functioning
      in patients with mental disorders. Although generally effective, some patients do
      not benefit from this rehabilitation and suffer from symptoms as well as
      functional impairment. This study aimed to identify patient-reported factors
      influencing activity and participation outcomes. SUBJECT AND METHODS: Five focus
      groups with N=23 former psychosomatic rehabilitation inpatients were conducted.
      The discussions focused on facilitators and barriers of treatment outcome. The
      material was analyzed inductively according to qualitative content analysis.
      Categories were derived from the material. RESULTS: Patients reported
      sociodemographic and clinical characteristics as well as personal factors,
      preparation before psychotherapy, and aspects of employment and health care as
      predictors of treatment success. CONCLUSION: A wide range of possible factors
      that influence the course of functioning from the patients' perspective were
      determined. These factors can be assigned to the ICF conceptual model. Clinician
      and researcher perspectives may complement these factors.

PMID- 27698553
TI  - Professionals' perception on the management of patients with dual disorders.
AB  - BACKGROUND: There is a need to evaluate the professionals' perception about the
      consequences of the lack of therapeutic adherence in the evolution of patients
      with co-occurring disorders. METHODS: An online survey, released on the
      Socidrogalcohol [Spanish Scientific Society for Research on Alcohol, Alcoholism
      and other Drug Addictions] and Sociedad Espanola de Patologia Dual [the Spanish
      Society of Dual Pathology] web pages, was answered by 250 professionals who work
      in different types of Spanish health centers where dual diagnosis patients are
      assisted. RESULTS: Most professionals perceived the existence of noncompliance
      among dual diagnosis patients. Almost all of these professionals (99%) perceived
      that noncompliance leads to a worsening of the progression of the patient's
      disorder, in both the exacerbation of mental disorders and the consumption of
      addictive substances. Most of the professionals (69.2%) considered therapeutic
      alliance as the main aspect to take into account to improve the prognosis in this
      population. The primary purpose of treatment must be the improvement of psychotic
      phase positive symptoms, followed by the control of behavior disorders, reduction
      of craving, improvement of social and personal performances, and reduction of
      psychotic-phase negative symptoms. CONCLUSION: Most professionals perceived low
      adherence among dual diagnosis patients. This lack of adherence is associated
      with a worsening of their disease evolution, which is reflected in exacerbations
      of the psychopathology and relapse in substance use. Therefore, we propose to
      identify strategies to improve adherence.

PMID- 27698555
TI  - Efficacy and safety of Chinese herbal medicine for chronic prostatitis associated
      with damp-heat and blood-stasis syndromes: a meta-analysis and literature review.
AB  - OBJECTIVE: The aim of this meta-analysis and systematic review is to evaluate the
      safety and efficacy of Chinese herbal medicine (CHM) for chronic prostatitis (CP)
      associated with damp-heat and blood-stasis syndromes. METHODS: An electronic
      search of 13 databases up to May 2016 was screened to identify randomized
      controlled trials comparing the safety and efficacy of CHM for the treatment of
      CP associated with damp-heat and blood-stasis syndromes. Studies reporting on
      effective rates, adverse events, National Institutes of Health chronic
      prostatitis symptom index (NIH-CPSI) scores, and symptom index of Chinese
      medicine for chronic prostatitis (SI-CM) scores as outcomes were included in the
      analysis. Data were analyzed by fixed- or random-effect models using the Review
      Manager software. RESULTS: Thirteen articles with the modified Jadad score >=4
      were identified. It was found that CHM was superior to placebo in increasing the
      efficacy (odds ratio: 6.72, 95% confidence interval [CI]: 2.78-9.48, P<0.00001)
      and reducing the SI-CM scores (standardized mean difference: -1.08, 95% CI: -1.35
      to -0.81, P<0.00001). Oral CHMs were significantly more effective than placebo at
      reducing NIH-CPSI scores, with a mean difference of -1.39 (95% CI: -1.87 to 
      0.92, P<0.00001). Nevertheless, no significant differences were found between
      Prostant and placebo (standardized mean difference: -0.23, 95% CI: -0.46 to 0.01,
      P=0.06). The frequency of adverse events associated with oral CHM was similar to
      that associated with placebo (risk ratio: 1.36, 95% CI: 0.72-2.55, P=0.34) and
      less than that associated with Prostant (risk ratio: 1.63, 95% CI: 1.14-2.34,
      P=0.008). CONCLUSION: Our novel analysis demonstrates that CHM ranks highest in
      terms of improvement of CP associated with damp-heat and blood-stasis syndromes.
      While Prostant showed some efficacy in this disorder, it was associated with a
      smaller reduction in NIH-CPSI scores. In conclusion, CHM monotherapy is safe and
      effective for the treatment of CP associated with damp-heat and blood-stasis
      syndromes.

PMID- 27698556
TI  - Digital life storybooks for people with dementia living in care homes: an
      evaluation.
AB  - BACKGROUND AND AIM: There is increasing interest in using information and
      communication technology to help older adults with dementia to engage in
      reminiscence work. Now, the feasibility of such approaches is beginning to be
      established. The purpose of this study was to establish an evidence-base for the
      acceptability and efficacy of using multimedia digital life storybooks with
      people with dementia in care homes, in comparison with conventional life
      storybooks, taking into account the perspectives of people with dementia, their
      relatives, and care staff. METHODS: Participatory design was used to create a
      life story movie based on a previously completed conventional life storybook with
      six older adults with dementia (four females; mean age 82 years). Relatives were
      involved in helping the participant to provide additional information and
      materials for the digital life storybook. In this multiple case study design,
      both quantitative and qualitative approaches were used. For quantitative
      purposes, a set of questionnaires that had been completed three times before and
      after the conventional life storybook was developed were repeated 4 weeks after
      the life story movie was completed. Semistructured interview questions were
      designed to collect feedback from participants, relatives, and care staff.
      RESULTS: The result indicated that five of the six participants showed additional
      improvement in measures of quality of life and autobiographical memory. All
      participants showed improvement or stability in depression scores. Thematic
      analysis showed that, participants, relatives, and care home staff viewed digital
      life storybooks as a very useful tool triggering memories and (largely) positive
      emotions. Participants' case vignettes were presented to document the impact of
      digital life storybook.

PMID- 27698557
TI  - Tai chi qigong as a means to improve night-time sleep quality among older adults
      with cognitive impairment: a pilot randomized controlled trial.
AB  - PURPOSE: Age-related cognitivee decline is a growing public health concern
      worldwide. More than a quarter of adults with cognitive impairment experience
      sleep disturbance. The objective of this pilot study was to evaluate the
      preliminary effects of tai chi qigong (TCQ) on improving the night-time sleep
      quality of older adults with cognitive impairment. PARTICIPANTS: Older adults
      with cognitive impairment who complain of sleep disturbance. METHODS: A
      randomized controlled trial with two groups. Fifty-two subjects were recruited
      from two district elderly community centers and randomly assigned to either the
      TCQ group (n=27) or the control group (n=25). The intervention group received TCQ
      training consisting of two 60-minute sessions each week for 2 months. The control
      group was advised to maintain their usual activities. Sleep quality was measured
      by the Chinese Pittsburgh Sleep Quality Index. Quality of life was measured by
      Short-form 12, cognitive functions measured by mini-mental state examination, and
      subjective memory deficits measured by the memory inventory for Chinese. RESULTS:
      Data were collected at baseline, 2 months, and 6 months. Significant results were
      noted at 6 months in the Chinese Pittsburgh Sleep Quality Index global score
      (P=0.004), sleep duration (P=0.003), habitual sleep efficiency (P=0.002), and the
      Short-form 12 mental health component (P<0.001). The TCQ participants reported
      better sleep quality and a better (quality of life) mental health component than
      the control group. CONCLUSION: TCQ can be considered a useful nonpharmacological
      approach for improving sleep quality in older adults with cognitive impairment.
      CLINICAL TRIAL REGISTRATION: CUHK_CCT00448
      (https://www2.ccrb.cuhk.edu.hk/registry/public/287).

PMID- 27698559
TI  - Efficacy and safety of tamsulosin hydrochloride 0.2 mg and combination of
      tamsulosin hydrochloride 0.2 mg plus solifenacin succinate 5 mg after
      transurethral resection of the prostate: a prospective, randomized controlled
      trial.
AB  - OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of
      tamsulosin hydrochloride 0.2 mg (TAM) and its combination with solifenacin
      succinate 5 mg (SOL) after transurethral resection of the prostate (TURP).
      PATIENTS AND METHODS: The patients were randomized into three groups: TURP (group
      1), TURP plus TAM (group 2), and TURP plus TAM + SOL (group 3). Patients in group
      2 and group 3 received medication for 4 weeks. The primary efficacy end points
      were the mean change in total International Prostate Symptom Score (IPSS) and
      IPSS subscores. The secondary end points included quality-of-life score,
      Overactive Bladder Symptom Score, and short-form voiding and storage score of
      International Continence Society. RESULTS: In total, 37 men (31.8%) in group 1,
      37 men (31.8%) in group 2, and 42 men (36.2%) in group 3 completed the study. In
      total IPSS, no significant improvement was seen from baseline to the end of
      treatment in groups 2 and 3 compared with group 1. However, in group 2, the
      decrement in the IPSS storage score was smaller than group 1 (P=0.02), and in
      group 3, the decrement in the IPSS voiding score was smaller than group 1
      (P=0.05). In groups 2 and 3 compared with group 1, improvements in the quality of
      life score, total score of Overactive Bladder Symptom Score, and short-form
      voiding score and storage score of International Continence Society were not
      statistically significant. CONCLUSION: Treatment with TAM and combination of TAM
      and SOL did not have significant additional benefits for lower urinary tract
      symptoms during the early recovery period after TURP.

PMID- 27698558
TI  - Effects of combined physical and cognitive training on fitness and
      neuropsychological outcomes in healthy older adults.
AB  - PURPOSE: Physical exercise and cognitive training have been shown to enhance
      cognition among older adults. However, few studies have looked at the potential
      synergetic effects of combining physical and cognitive training in a single
      study. Prior trials on combined training have led to interesting yet equivocal
      results. The aim of this study was to examine the effects of combined physical
      and cognitive interventions on physical fitness and neuropsychological
      performance in healthy older adults. METHODS: Seventy-six participants were
      randomly assigned to one of four training combinations using a 2*2 factorial
      design. The physical intervention was a mixed aerobic and resistance training
      program, and the cognitive intervention was a dual-task (DT) training program.
      Stretching and toning exercises and computer lessons were used as active control
      conditions. Physical and cognitive measures were collected pre- and
      postintervention. RESULTS: All groups showed equivalent improvements in measures
      of functional mobility. The aerobic-strength condition led to larger effect size
      in lower body strength, independently of cognitive training. All groups showed
      improved speed of processing and inhibition abilities, but only participants who
      took part in the DT training, independently of physical training, showed
      increased task-switching abilities. The level of functional mobility after
      intervention was significantly associated with task-switching abilities.
      CONCLUSION: Combined training did not yield synergetic effects. However, DT
      training did lead to transfer effects on executive performance in
      neuropsychological tests. Both aerobic-resistance training and stretching-toning
      exercises can improve functional mobility in older adults.

PMID- 27698560
TI  - The effect of domiciliary noninvasive ventilation on clinical outcomes in stable
      and recently hospitalized patients with COPD: a systematic review and meta
      analysis.
AB  - INTRODUCTION: Noninvasive ventilation (NIV) improves survival among patients with
      hypercapnic respiratory failure in hospital, but evidence for its use in
      domiciliary settings is limited. A patient's underlying risk of having an
      exacerbation may affect any potential benefit that can be gained from domiciliary
      NIV. This is the first comprehensive systematic review to stratify patients based
      on a proxy for exacerbation risk: patients in a stable state and those
      immediately post-exacerbation hospitalization. METHODS: A systematic review of
      nonrandomized and randomized controlled trials (RCTs) was undertaken in order to
      compare the relative effectiveness of different types of domiciliary NIV and
      usual care on hospital admissions, mortality, and health-related quality of life.
      Standard systematic review methods were used for identifying studies (until
      September 2014), quality appraisal, and synthesis. Data were presented in forest
      plots and pooled where appropriate using random-effects meta-analysis. RESULTS:
      Thirty-one studies were included. For stable patients, there was no evidence of a
      survival benefit from NIV (relative risk [RR] 0.88 [0.55, 1.43], I2=60.4%, n=7
      RCTs), but there was a possible trend toward fewer hospitalizations (weighted
      mean difference -0.46 [-1.02, 0.09], I2=59.2%, n=5 RCTs) and improved health
      related quality of life. For posthospital patients, survival benefit could not be
      demonstrated within the three RCTs (RR 0.89 [0.53, 1.49], I2=25.1%), although
      there was evidence of benefit from four non-RCTs (RR 0.45 [0.32, 0.65], I2=0%).
      Effects on hospitalizations were inconsistent. Post hoc analyses suggested that
      NIV-related improvements in hypercapnia were associated with reduced hospital
      admissions across both populations. Little data were available comparing
      different types of NIV. CONCLUSION: The effectiveness of domiciliary NIV remains
      uncertain; however, some patients may benefit. Further research is required to
      identify these patients and to explore the relevance of improvements in
      hypercapnia in influencing clinical outcomes. Optimum time points for commencing
      domiciliary NIV and equipment settings need to be established.

PMID- 27698561
TI  - Influence of country-level differences on COPD prevalence.
AB  - PURPOSE: Studies suggest that COPD prevalence may vary between countries. We
      conducted an ecological study of data from COPD prevalence articles to assess the
      influence of differences in country-level risk factors on COPD prevalence.
      PATIENTS AND METHODS: Our study covered English language articles published
      during 2003-2014. Qualified articles used spirometry to assess COPD prevalence
      and used representative samples from national or subnational populations.
      Stepwise binomial regression was used to analyze associations between study- and
      country-level factors and COPD prevalence. RESULTS: Eighty articles provided
      1,583 measures of COPD prevalence for subjects in different sex, age, and smoking
      categories for 112 districts in 41 countries. Adjusted prevalence rates for COPD
      were significantly lower for Australia/New Zealand and the Mediterranean and
      significantly higher for Latin America, compared to North America, Southeast
      Asia, and Northern Europe. Country-level socioeconomic development variables had
      an uneven and mixed association with COPD prevalence. High elevation above sea
      level was shown to be a protective factor for COPD. Study-level variables for the
      established risk factors of sex, age, and smoking explained 64% of variability in
      COPD prevalence. Country-level risk factors raised the explanatory power to 72%.
      Approximately 28% of worldwide variability in COPD prevalence remained
      unexplained. CONCLUSION: Our study suggests that COPD prevalence varies across
      world regions, even after adjustment for established risk factors. Major country
      level risk factors contributing to the worldwide epidemic of COPD remain to be
      investigated.

PMID- 27698564
TI  - Epilepsia partialis continua present with shoulder joint-trunk-hip joint rhythmic
      clonic seizure: a case report.
AB  - Epilepsia partialis continua (EPC) is a particular type of epilepsy which is
      distinguished from "common epilepsy" by its characteristic semiological features.
      However, unusual manifestations should be described in order to give awareness at
      clinical diagnosis. In this case report we describe a rare EPC case not
      previously reported, in which left shoulder joint-trunk-hip joint jerk was
      present for 1 week. Abnormal electroencephalogram and cerebrospinal fluid results
      supported a diagnosis of viral encephalitis. Antiepileptic treatment seemed
      effective. Our report emphasizes that a detailed functional anatomical analysis
      and synchronized electroencephalogram discharge should be done to avoid
      misdiagnosis in patients with synchronic shoulder-trunk-hip jerk symptoms.

PMID- 27698562
TI  - Multifunctional nanocomposite based on halloysite nanotubes for efficient
      luminescent bioimaging and magnetic resonance imaging.
AB  - A novel multifunctional halloysite nanotube (HNT)-based Fe3O4@HNT
      polyethyleneimine-Tip-Eu(dibenzoylmethane)3 nanocomposite (Fe-HNT-Eu NC) with
      both photoluminescent and magnetic properties was fabricated by a simple one-step
      hydrothermal process combined with the coupling grafting method, which exhibited
      high suspension stability and excellent photophysical behavior. The as-prepared
      multifunctional Fe-HNT-Eu NC was characterized using various techniques. The
      results of cell viability assay, cell morphological observation, and in vivo
      toxicity assay indicated that the NC exhibited excellent biocompatibility over
      the studied concentration range, suggesting that the obtained Fe-HNT-Eu NC was a
      suitable material for bioimaging and biological applications in human hepatic
      adenocarcinoma cells. Furthermore, the biocompatible Fe-HNT-Eu NC displayed
      superparamagnetic behavior with high saturation magnetization and also functioned
      as a magnetic resonance imaging (MRI) contrast agent in vitro and in vivo. The
      results of the MRI tests indicated that the Fe-HNT-Eu NC can significantly
      decrease the T2 signal intensity values of the normal liver tissue and thus make
      the boundary between the normal liver and transplanted cancer more distinct, thus
      effectively improving the diagnosis effect of cancers.

PMID- 27698565
TI  - Economic evaluation of eribulin as second-line treatment for metastatic breast
      cancer in South Korea.
AB  - BACKGROUND: Metastatic breast cancer (MBC) is associated with poor prognosis,
      particularly for those patients with human epidermal growth factor receptor
      (HER2)-negative tumor. Similar to the rest of the world, treatment options are
      limited in South Korea following first-line chemotherapy with anthracyclines
      and/or taxanes. This study examined the cost-effectiveness and cost-utility of
      eribulin in South Korean patients with HER2-negative MBC who have progressed
      after usage of at least one chemotherapeutic regimen for advanced disease (second
      line therapy). METHODS: A partition survival model was developed from the
      perspective of the South Korean health care system. The economic impact of
      introducing eribulin as second-line therapy for HER2-negative MBC was compared to
      that of capecitabine and vinorelbine. The analysis estimated incremental cost per
      life-year (LY), that is, cost-effectiveness, and cost per quality-adjusted life
      year (QALY), that is, cost-utility, of eribulin for management of HER2-negative
      MBC in South Korea. The model accounted for overall survival, progression-free
      survival, drug costs, grade 3/4 adverse events, and health care utilization.
      Deterministic and probabilistic sensitivity analyses were performed to identify
      uncertainty in the results of the economic evaluation. RESULTS: Second-line
      eribulin was associated with greater benefits in terms of LY and QALY, compared
      to capecitabine and vinorelbine. The incremental cost-effectiveness ratio was
      ?10.5M (approximately USD 9,200) per LY, and the incremental cost-utility ratio
      was ?17M (approximately USD 14,800) per QALY in the basecase analysis. The
      incremental cost-utility ratio ranged from ?12M (USD 10,461) to ?27M (USD 23,538)
      per QALY in the deterministic sensitivity analysis. In the probabilistic
      sensitivity analysis, >99% of the simulations were below ?50M (USD 42,300), and
      the lower and upper 95% confidence intervals were ?3M (USD 2,600) and ?24M (USD
      20,900) per QALY, respectively. CONCLUSION: There currently exist a limited
      number of treatment choices for women with HER2-negative MBC. Eribulin is a cost
      effective option for second-line therapy in South Korea and should be added to
      the current indications for reimbursement.

PMID- 27698563
TI  - Functionalized immunostimulating complexes with protein A via lipid vinyl
      sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing
      breast cancer cells.
AB  - BACKGROUND: Around 20%-30% of breast cancers overexpress the proto-oncogene human
      epidermal growth receptor 2 (HER2), and they are characterized by being very
      invasive. Therefore, many current studies are focused on testing new therapies
      against tumors that overexpress this receptor. In particular, there exists major
      interest in new strategies to fight breast cancer resistant to trastuzumab
      (Tmab), a humanized antibody that binds specifically to HER2 interfering with its
      mitogenic signaling. Our team has previously developed immunostimulating
      complexes (ISCOMs) as nanocapsules functionalized with lipid vinyl sulfones,
      which can incorporate protein A and bind to G immunoglobulins that makes them
      very flexible nanocarriers. METHODS AND RESULTS: The aim of this in vitro study
      was to synthesize and evaluate a drug delivery system based on protein A
      functionalized ISCOMs to target HER2-overexpressing cells. We describe the
      preparation of ISCOMs, the loading with the drugs doxorubicin and paclitaxel, the
      binding of ISCOMs to alkyl vinyl sulfone-protein A, the coupling of Tmab, and the
      evaluation in both HER2-overexpressing breast cancer cells (HCC1954) and non
      overexpressing cells (MCF-7) by flow cytometry and fluorescence microscopy.
      Results show that the uptake is dependent on the level of overexpression of HER2,
      and the analysis of the cell viability reveals that targeted drugs are selective
      toward HCC1954, whereas MCF-7 cells remain unaffected. CONCLUSION: Protein A
      functionalized ISCOMs are versatile carriers that can be coupled to antibodies
      that act as targeting agents to deliver drugs. When coupling to Tmab and loading
      with paclitaxel or doxorubicin, they become efficient vehicles for the selective
      delivery of the drug to Tmab-resistant HER2-overexpressing breast cancer cells.
      These nanoparticles may pave the way for the development of novel therapies for
      poor prognosis resistant patients.

PMID- 27698566
TI  - Calciphylaxis in peritoneal dialysis patients: a single center cohort study.
AB  - BACKGROUND: Calciphylaxis is a rare but devastating condition in end-stage renal
      disease (ESRD) patients. Most research in the field of calciphylaxis is focused
      on hemodialysis (HD) patients; however, data on calciphylaxis incidence, risk
      factors, and mortality in peritoneal dialysis (PD) patients are limited. METHODS:
      In this cohort study, we examined data from adult patients who initiated PD for
      ESRD management at our institute's PD unit from January 2001 to December 2015.
      Associations with the development of calciphylaxis were examined for clinical,
      laboratory, and medication exposures. Incidence of calciphylaxis and mortality in
      PD patients who developed calciphylaxis were analyzed. Treatments administered to
      treat calciphylaxis in PD patients were summarized. RESULTS: In this cohort of 63
      patients, 7 patients developed calciphylaxis (incidence rate: 9.0 per 1,000
      patient-years). Median age of PD patients who developed calciphylaxis was 50
      years, 57% were white, 71% females, and 71% were previously on HD. Female sex,
      obesity, HD as a prior dialysis modality, recurrent hypotension, elevated time
      averaged serum phosphorous levels, reduced time-averaged serum albumin levels,
      and warfarin therapy were associated with increased calciphylaxis risk in
      univariate logistic regression analyses. Intravenous sodium thiosulfate was
      administered in 57% of PD patients who developed calciphylaxis. One-year
      mortality in PD patients who developed calciphylaxis was 71% despite multimodal
      treatment including sodium thiosulfate, hyperbaric oxygen, cinacalcet, and wound
      debridement. CONCLUSION: Calciphylaxis is a rare but frequently fatal condition
      in PD patients. Our study provides critical early insights into calciphylaxis
      incidence, risk factors, and prognosis in PD patients. Sample size and
      characteristics of patients included in our study limit generalizability to
      overall PD population and warrant examination in larger independent studies.

PMID- 27698568
TI  - Atypical scleromyxedema presenting with cutaneous and cardiovascular
      manifestations.
AB  - Scleromyxedema is part of a group of cutaneous mucinoses, characterized by a
      generalized papular eruption, dermal mucin deposition, and an increase in dermal
      collagen. This condition can be localized as discrete papular lichen myxedematous
      skin or as a systemic condition usually associated with paraproteinaemia. To
      date, there is no unifying treatment and is limited by rarity, small number of
      case reports, and the lack of randomized controlled trials. We describe the case
      of a 56-year-old gentleman with features of scleromyxedema who had cutaneous and
      cardiac involvement, and significant mediastinal lymphadenopathy without
      monoclonal gammopathy.

PMID- 27698567
TI  - Managing hyperthyroidism in pregnancy: current perspectives.
AB  - Hyperthyroidism in women who are of childbearing age is predominantly of
      autoimmune origin and caused by Graves' disease. The physiological changes in the
      maternal immune system during a pregnancy may influence the development of this
      and other autoimmune diseases. Furthermore, pregnancy-associated physiological
      changes influence the synthesis and metabolism of thyroid hormones and challenge
      the interpretation of thyroid function tests in pregnancy. Thyroid hormones are
      crucial regulators of early development and play an important role in the
      maintenance of a normal pregnancy and in the development of the fetus,
      particularly the fetal brain. Untreated or inadequately treated hyperthyroidism
      is associated with pregnancy complications and may even program the fetus to long
      term development of disease. Thus, hyperthyroidism in pregnant women should be
      carefully managed and controlled, and proper management involves different
      medical specialties. The treatment of choice in pregnancy is antithyroid drugs
      (ATDs). These drugs are effective in the control of maternal hyperthyroidism, but
      they all cross the placenta, and so need careful management and control during
      the second half of pregnancy considering the risk of fetal hyper- or
      hypothyroidism. An important aspect in the early pregnancy is that the
      predominant side effect to the use of ATDs in weeks 6-10 of pregnancy is birth
      defects that may develop after exposure to available types of ATDs and may be
      severe. This review focuses on four current perspectives in the management of
      overt hyperthyroidism in pregnancy, including the etiology and incidence of the
      disease, how the diagnosis is made, the consequences of untreated or inadequately
      treated disease, and finally how to treat overt hyperthyroidism in pregnancy.

PMID- 27698569
TI  - Robotic magnetic navigation for ablation of human arrhythmias.
AB  - Radiofrequency treatment represents the first choice of treatment for
      arrhythmias, in particular complex arrhythmias and especially atrial
      fibrillation, due to the greater benefit/risk ratio compared to antiarrhythmic
      drugs. However, complex arrhythmias such as atrial fibrillation require long
      procedures with additional risks such as X-ray exposure or serious complications
      such as tamponade. Given this context, the treatment of arrhythmias using robotic
      magnetic navigation entails a technique well suited to complex arrhythmias on
      account of its efficacy, reliability, significant reduction in X-ray exposure for
      both patient and operator, as well as a very low risk of perforation. As ongoing
      developments will likely improve results and procedure times, this technology
      will become one of the most modern technologies for treating arrhythmias. Based
      on the literature, this review summarizes the advantages and limitations of
      robotic magnetic navigation for ablation of human arrhythmias.

PMID- 27698570
TI  - New species of Uvariopsis (Annonaceae) and Laccosperma (Arecaceae/Palmae) from
      Monts de Cristal, Gabon.
AB  - Monts de Cristal National Park in northwest Gabon is one of the most species rich
      places in Central Africa. Here, we describe two new species, one in Annonaceae
      and one in palms. Uvariopsis citrata Couvreur & Niangadouma, sp. nov. is unique
      in the genus by emitting a strong lemon scent from the crushed leaves and young
      branches. Laccosperma cristalensis Couvreur & Niangadouma, sp. nov. is a rattan
      that lacks acanthophylls on the cirrus and has few pinnae. Complete descriptions,
      photographic illustrations, ecological information and preliminary IUCN
      conservation status are provided. For both species a data deficient (DD) status
      is proposed. These new species underline once again that the Monts de Cristal
      National Park is yet incompletely known botanically.

PMID- 27698571
TI  - Seed micromorphology of Orchis Tourn. ex L. (Orchidaceae) and allied genera
      growing in Edirne province, Turkey.
AB  - In this study, the seed micromorphologies of eight taxa of Anacamptis, Neotinea
      and Orchis growing around Edirne province (Turkey) were investigated using light
      microscopy and scanning electron microscopy (SEM). Slides prepared with glycerin
      jelly were used for measurements under the light microscope and fine details of
      seed testae characteristics were observed with SEM. Seeds of the investigated
      orchid taxa are fusiform shaped and of different shades of brown. Their lengths
      and widths are different among the taxa and range between 0.263-0.640 mm and
      0.118-0.208 mm, respectively. Testa surfaces of Orchis mascula subsp. mascula,
      Orchis purpurea subsp. purpurea and Orchis simia subsp. simia, are smooth while
      those of Anacamptis coriophora, Anacamptis laxiflora subsp. laxiflora, Anacamptis
      morio subsp. morio, Anacamptis papilionacea and Neotinea tridentata subsp.
      tridentata are reticulate. An identification key based on seed morphologies and
      sizes is suggested for the first time, including testae structures of orchids
      growing in Edirne province. The overall results of the study showed that
      morphological structures of orchid's seeds could be used as diagnostic characters
      in identification.

PMID- 27698572
TI  - GuiaTreeKey, a multi-access electronic key to identify tree genera in French
      Guiana.
AB  - The tropical rainforest of Amazonia is one of the most species-rich ecosystems on
      earth, with an estimated 16000 tree species. Due to this high diversity,
      botanical identification of trees in the Amazon is difficult, even to genus,
      often requiring the assistance of parataxonomists or taxonomic specialists.
      Advances in informatics tools offer a promising opportunity to develop user
      friendly electronic keys to improve Amazonian tree identification. Here, we
      introduce an original multi-access electronic key for the identification of 389
      tree genera occurring in French Guiana terra-firme forests, based on a set of 79
      morphological characters related to vegetative, floral and fruit characters. Its
      purpose is to help Amazonian tree identification and to support the dissemination
      of botanical knowledge to non-specialists, including forest workers, students and
      researchers from other scientific disciplines. The electronic key is accessible
      with the free access software Xper2, and the database is publicly available on
      figshare: https://figshare.com/s/75d890b7d707e0ffc9bf (doi:
      10.6084/m9.figshare.2682550).

PMID- 27698573
TI  - Hoya isabelchanae Rodda & Simonsson, a new, showy species of Hoya R.Br.
      (Apocynaceae, Asclepiadoideae) with pomegranate red flowers from Sulawesi,
      Indonesia.
AB  - A new species of Hoya R.Br. from Sulawesi (Indonesia), Hoya isabelchanae Rodda &
      Simonsson, is described and illustrated. It is one of the largest flowered
      species in Hoya section Acanthostemma (Blume) Kloppenb. Its flowers are of
      comparable size to those of Hoya benchaii Gavrus et al., Hoya kloppenburgii
      T.Green, Hoya rundumensis (T.Green) Rodda & Simonsson and Hoya sigillatis T.Green
      ssp. sigillatis, all from Borneo. Among Sulawesi species it is compared with the
      vegetatively similar Hoya brevialata Kleijn & van Donkelaar and Hoya pallilimba
      Kleijn & van Donkelaar.

PMID- 27698575
TI  - Cirsium semzinanicum (Asteraceae), a new species from Hakkari, Turkey.
AB  - Cirsium semzinanicumsp. nov. (Asteraceae) is described as a new species from
      Hakkari, Turkey. The new species is a part of the sect. Epitrachys (Cardueae) and
      similar to Cirsium karduchorum, from which it differs in morphological characters
      such as leaves, involucre, phyllaries, corolla, achens and pollen morphology.
      Geographical distribution, habitat and IUCN conservation status of this species
      are given.

PMID- 27698574
TI  - Vegetation and fire in lowland dry forest at Wa'ahila Ridge on O'ahu, Hawai'i.
AB  - Long-term ecological studies are critical for providing key insights in ecology,
      environmental change, natural resource management and biodiversity conservation.
      However, island fire ecology is poorly understood. No previous studies are
      available that analyze vegetative changes in burned and unburned dry forest
      remnants on Wa'ahila Ridge, Hawai'i. This study investigates vegetation
      succession from 2008 to 2015, following a fire in 2007 which caused significant
      differences in species richness, plant density, and the frequency of woody, herb,
      grass, and lichens between burned and unburned sites. These findings infer that
      introduced plants have better competitive ability to occupy open canopy lands
      than native plants after fire. This study also illustrates the essential
      management need to prevent alien plant invasion, and to restore the native
      vegetation in lowland areas of the Hawaiian Islands by removing invasive species
      out-planting native plants after fire.

PMID- 27698576
TI  - Taxonomic implications from morphological and anatomical studies in the section
      Stenodiptera from the genus Grammosciadium (Apiaceae).
AB  - Grammosciadium pterocarpum subsp. bilgilii and Grammosciadium pterocarpum subsp.
      sivasicum from Turkey are herein described as two new subspecies, and the species
      Grammosciadium schischkinii is synonymied under Grammosciadium pterocarpum subsp.
      pterocarpum. Quantitative variation of morphological and anatomical characters
      have been analysed to provide discriminative characters between the taxa of
      section Stenodiptera and to provide a key to the species. The taxonomic status of
      the taxa has been discussed in light of these morphological and fruit anatomical
      data using multivariate statistics such as MANOVA and Principal Component
      Analysis. The results are also used to present a critical discussion of
      characters used to distinguish and determine different taxa within
      Grammosciadium. MANOVA showed that ten characters, except stylopodium and style
      length, differed significantly among the taxa, and the results were confirmed by
      Tukey tests and PCA analysis (except the character of fruit number). However,
      only ranges of the characters of sepal length, fruit length, fruit width, fruit
      width/wing width ratio, and width of fruit wing are not overlapped. Qualitative
      characters of petiolate stipular segments of lower leaves and presence of
      funicular oil ducts in transvers section of mericarps were found as diagnostic
      characters.

PMID- 27698577
TI  - The mosses (Bryophyta) of Capitan Prat Province, Aisen Region, southern Chile.
AB  - The bryophytes of Capitan Prat province have remained one of the least explored
      in Chile. The eventual construction of several dams on the rivers Baker and
      Pascua required prospection of all groups of organisms including bryophytes, work
      that was facilitated by the recent construction of vehicular roads that now offer
      easy access to previously almost unaccessible locations. The results of intense
      bryophyte collecting during the austral summer of 2007 are here presented. A
      total of 260 moss taxa are reported for the province, corresponding to 256
      species and four infraspecific taxa, of which 211 are new records for the
      province, 54 are new for Aisen Region, and two are new records for continental
      Chile (Pohlia longicollis (Hedw.) Lindb. and Rigodium toxarion var. robustum
      (Broth.) Zomlefer). Twelve species extend their known distribution ranges to the
      north, whereas 49 extend them to the south.

PMID- 27698578
TI  - Alysicarpus poklianus (Fabaceae, Desmodieae), a new species from India.
AB  - A new species, Alysicarpus poklianus Gholami & Pandey from Sinhgarh, Maharashtra,
      India is described. It is morphologically most similar to Alysicarpus hamosus but
      differs in having ovate leaves, rounded-ovate bracts, larger size of calyx, pods
      comprising 5-7 longer than broad joints with easily separable septa. In this
      study, a comprehensive description, and identification key of Alysicarpus
      poklianus are provided.

PMID- 27698579
TI  - Anatomical and morphological spine variation in Gymnocalycium kieslingii subsp.
      castaneum (Cactaceae).
AB  - Although spine variation within cacti species or populations is assumed to be
      large, the minimum sample size of different spine anatomical and morphological
      traits required for species description is less studied. There are studies where
      only 2 spines were used for taxonomical comparison amnog species. Therefore, the
      spine structure variation within areoles and individuals of one population of
      Gymnocalycium kieslingii subsp. castaneum (Ferrari) Slaba was analyzed. Fifteen
      plants were selected and from each plant one areole from the basal, middle and
      upper part of the plant body was sampled. A scanning electron microscopy was used
      for spine surface description and a light microscopy for measurements of spine
      width, thickness, cross-section area, fiber diameter and fiber cell wall
      thickness. The spine surface was more visible and damaged less in the upper part
      of the plant body than in the basal part. Large spine and fiber differences were
      found between upper and lower parts of the plant body, but also within single
      areoles. In general, the examined traits in the upper part had by 8-17% higher
      values than in the lower parts. The variation of spine and fiber traits within
      areoles was lower than the differences between individuals. The minimum sample
      size was largely influenced by the studied spine and fiber traits, ranging from 1
      to 70 spines. The results provide pioneer information useful in spine sample
      collection in the field for taxonomical, biomechanical and structural studies.
      Nevertheless, similar studies should be carried out for other cacti species to
      make generalizations. The large spine and fiber variation within areoles observed
      in our study indicates a very complex spine morphogenesis.

PMID- 27698580
TI  - Jasminanthes xuanlienensis (Apocynaceae, Asclepiadoideae), a new species from
      Vietnam.
AB  - Jasminanthes xuanlienensis (Apocynaceae, Asclepiadoideae), a new species from
      Vietnam is described, illustrated and compared with its five congeners.
      Jasminanthes xuanlienensis differs distinctly from congeners by the longer
      peduncles (14-18 cm vs. 4 cm at most in Jasminanthes pilosa and Jasminanthes
      saxatilis, salmon-pink color of the inner corolla lobes (white or greenish in the
      other species), and corolla tube length (12.0-14.5 mm vs. shorter or longer in
      congeners).

PMID- 27698581
TI  - Lithocarpus dahuoaiensis (Fagaceae), a new species from Lam Dong Province,
      Vietnam.
AB  - Lithocarpus dahuoaiensis Ngoc & L. V. Dung, a new species from the Central
      highland of Vietnam, is described and illustrated. The new species is
      morphologically similar to Lithocarpus macphailii (M. R. Hend.) Barnett or
      Lithocarpus encleisocarpus (Korth.) A. Camus in having completely entire leaf
      margin, solitary cupule, long stalks of fruits, deeply cup-shaped or turbinate
      cupules, with a number of horizontal filiform lines. The species differs in its
      nut enclosure ca. 1/2 - 2/3 of the nut, adaxially glabrous leaf blades, secondary
      veins 11-12 pairs and faintly to very faintly visible hairs on the outside of the
      cupule. A table showing the morphological comparison of Lithocarpus dahuoaiensis
      with Lithocarpus macphailii and Lithocarpus encleisocarpus is also provided.

PMID- 27698582
TI  - Diplycosia platyphylla (Ericaceae), a new species from Mindanao, Philippines.
AB  - Diplycosia platyphylla P.W.Fritsch, a new species from Mindanao Island,
      Philippines, is described and illustrated. This species is most similar to the
      Bornean Diplycosia urceolata but differs by its green or slightly flushed pink
      petioles 4-7 mm long, wider leaf blades, acute calyx lobe apices, and lavender
      mature fruiting calyx. The new species is known only from a single collection
      made from Mount Apo in North Cotabato Province, southern Mindanao.

PMID- 27698583
TI  - Onosma anatolica, a new species of Boraginaceae from Turkey.
AB  - Onosma anatolica Binzet, is described and illustrated as a new species from Nigde
      province in southern Anatolia, Turkey. It belongs to sect. Onosma L. subsect.
      Asterotricha (Boiss.) Gurke. The new species is closely related to Onosma
      subulifolia Riedl from which it is distinguished. Onosma anatolica is readily
      distinguished from Onosma subulifolia by its sterile shoots, the green-grey stem
      indumentum, longer bracts, yellow and puberulous petals. The IUCN threat category
      of Onosma anatolica is determined as "CR (Critically Endangered)". A distribution
      map and anidentification key for Onosma anatolica and Onosma subulifolia
      supplement the study.

PMID- 27698584
TI  - Melicope oppenheimeri, section Pelea (Rutaceae), a new species from West Maui,
      Hawaiian Islands: with notes on its ecology, conservation, and phylogenetic
      placement.
AB  - Melicope oppenheimeri K.R. Wood, Appelhans & W.L. Wagner (section Pelea (A. Gray)
      Hook. f., Rutaceae), a rare endemic tree from West Maui, Hawaiian Islands, is
      described and illustrated with notes on its ecology, conservation, and
      phylogenetic placement. The new species differs from Hawaiian congeners by its
      carpels basally connate 1/5, narrowed into a strongly reflexed beak 10-15 mm
      long. It also differs in a combination of leaves with 7-10 pair of secondary
      veins; cymes to 3 cm long; peduncles 5-6.5 mm long; flowers perfect; capsules 4-9
      * 40-52 mm; and a densely appressed short-sericeous ovary. Melicope oppenheimeri
      is known only from an isolated cliff-base plateau in upper Waihe'e Valley, West
      Maui. Its discovery brings the number of recognized Melicope J.R. Forst. & G.
      Forst. species in the Hawaiian Islands to 49. A table is included indicating the
      conservation status of Hawaiian Melicope and Platydesma H. Mann., which is nested
      within Melicope sect. Pelea. Melicope oppenheimeri falls into the IUCN Critically
      Endangered (CR) Red List category.

PMID- 27698585
TI  - Tulipa cinnabarina subsp. toprakii (Liliaceae), a new subspecies from
      southwestern Anatolia.
AB  - A new subpecies, Tulipa cinnabarina subsp. toprakii subsp. nov. (Liliaceae) from
      Turkey is described. Diagnostic characters, descriptions, detailed illustrations,
      geographical distribution, conservation status and ecological observations on the
      new taxon are provided. It is also compared with the closely related Tulipa
      cinnabarina subsp. cinnabarina.

PMID- 27698586
TI  - A nonet of novel species of Monanthotaxis (Annonaceae) from around Africa.
AB  - As part of an ongoing revision of the genus Monanthotaxis Baill. (Annonaceae),
      nine new species are described and one variety is reinstated to species rank. Two
      new species from West Africa (Monanthotaxis aquila P.H.Hoekstra, sp. nov. and
      Monanthotaxis atewensis P.H.Hoekstra, sp. nov.), four new species from Central
      Africa (Monanthotaxis couvreurii P.H.Hoekstra, sp. nov., Monanthotaxis
      latistamina P.H.Hoekstra, sp. nov., Monanthotaxis tripetala P.H.Hoekstra, sp.
      nov. and Monanthotaxis zenkeri P.H.Hoekstra, sp. nov.), one new species from
      Tanzania (Monanthotaxis filipes P.H.Hoekstra, sp. nov.), one new species from the
      area around Maputo (Monanthotaxis maputensis P.H.Hoekstra, sp. nov.), one new
      species from the Comoro Islands (Monanthotaxis komorensis P.H.Hoekstra, sp. nov.)
      and Monanthotaxis klainei (Engl.) Verdc. var. angustifolia (Boutique) Verdc. is
      raised to species level leading to the replacement name Monanthotaxis atopostema
      P.H.Hoekstra, nom. nov. (not Monanthotaxis angustifolia (Exell) Verdc.). Complete
      descriptions, comparisons with related species, ecological information and IUCN
      conservation assessments are given for the new species. Five species were
      classified as critical endangered, two species as endangered, one as vulnerable
      and one as least concern, warranting the need of further collecting and studying
      those species.

PMID- 27698587
TI  - Flora-On: Occurrence data of the vascular flora of mainland Portugal.
AB  - The Flora-On dataset currently includes 253,310 occurrence records for the class
      Embryopsidae (vascular plants), comprising data collated via the platform
      http://flora-on.pt/ relating to observation records of vascular plants across
      mainland Portugal. Observations are uploaded directly to the database primarily
      by experienced botanists and naturalists, typically on a weekly basis, and
      consist of geo-referenced data points for species (or infraspecific taxa) along
      with their date of observation and phenological state. The Flora-On project aims
      to compile and make publicly accessible chorological, ecological, morphological
      and photographic information for the entire vascular flora of Portugal. The
      project's website offers powerful query and visualization capabilities, of which
      we highlight the probabilistic bioclimatic and phenological queries which operate
      based on the empirical density distributions of species in those variables. Flora
      On was created and continues to be maintained by volunteers who are Associate
      members of Sociedade Portuguesa de Botanica (Botanical Society of Portugal).
      Given its focus on research-grade and current data, the Flora-On project
      represents a significant contribution to the knowledge of the present
      distribution and status of the Portuguese flora.

PMID- 27698588
TI  - Typification of species names in Adenocaulon and Eriachaenium
      (Compositae/Asteraceae, Subfamily Mutisioideae, Tribe Mutisieae, Subtribe
      Adenocaulinae).
AB  - During the course of a recent research project on Adenocaulon and Eriachaenium it
      became apparent that some of the species names had not been typified. In this
      study we located and designated as much type material as possible for these two
      genera. We indicate holotypes or lectotypes where appropriate, including one for
      the type of the genus Adenocaulon.

PMID- 27698589
TI  - Dichodon parvipetalum, a new combination for the Chinese Caryophyllaceae.
AB  - The generic name Dichodon (Bartl. ex Rchb.) Rchb. was previously reinstated based
      on results from recent molecular phylogenetic studies. Accordingly, Dichodon
      parvipetalum (Hosok.) G. Yao, a new combination for the species Cerastium
      parvipetalum Hosok. is proposed.

PMID- 27698590
TI  - Dosimetric feasibility of an "off-breast isocenter" technique for whole-breast
      cancer radiotherapy.
AB  - AIM: To investigate the viability of placing the treatment isocenter at the
      patient midline for breast cancer radiotherapy in order to avoid the risk of
      collisions during image-guided setup and treatment delivery. BACKGROUND: The use
      of kilovoltage orthogonal setup images has spread in last years in breast
      radiotherapy. There is a potential risk of an imaging system-patient collision
      when the isocenter is laterally placed. MATERIALS AND METHODS: Twenty IMRT plans
      designed by placing the isocenter within the breast volume ("plan_ref"), were
      retrospectively replanned by shifting the isocenter at the patient's midline
      ("plan_off-breast"). An integrated simultaneous boost (SIB) technique was used.
      Multiple metrics for the planning target volumes (PTVs) and organs at risk (OARs)
      were compared for both approaches using a paired t test. RESULTS: Comparing
      plan_ref vs. plan_off-breast, no significant differences in PTV coverage (V95%)
      were found (96.5% vs. 96.2%; p = 0.361 to PTVbreast; 97.0% vs. 97.0%; p = 0.977
      to PTVtumor_bed). With regard to OARs, no substantial differences were observed
      in any analyzed metric: V5Gy (30.3% vs. 31.4%; p = 0.486), V20Gy (10.3% vs.
      10.3%; p = 0.903) and mean dose (7.1 Gy vs. 7.1 Gy; p = 0.924) to the ipsilateral
      lung; V5Gy (11.2% vs. 10.0%; p = 0.459), V30Gy (0.7% vs. 0.6%; p = 0.251) and
      mean dose (2.3 Gy vs. 2.2 Gy; p = 0.400) to the heart; and average dose to the
      contralateral breast (0.4 Gy vs. 0.5 Gy; p = 0.107). CONCLUSIONS: The off-breast
      isocenter solution resulted in dosimetrically comparable plans as the reference
      technique, avoiding the collision risk during the treatment session.

PMID- 27698591
TI  - SPIDERplan: A tool to support decision-making in radiation therapy treatment plan
      assessment.
AB  - AIM: In this work, a graphical method for radiotherapy treatment plan assessment
      and comparison, named SPIDERplan, is proposed. It aims to support plan approval
      allowing independent and consistent comparisons of different treatment
      techniques, algorithms or treatment planning systems. BACKGROUND: Optimized plans
      from modern radiotherapy are not easy to evaluate and compare because of their
      inherent multicriterial nature. The clinical decision on the best treatment plan
      is mostly based on subjective options. MATERIALS AND METHODS: SPIDERplan combines
      a graphical analysis with a scoring index. Customized radar plots based on the
      categorization of structures into groups and on the determination of individual
      structures scores are generated. To each group and structure, an angular
      amplitude is assigned expressing the clinical importance defined by the radiation
      oncologist. Completing the graphical evaluation, a global plan score, based on
      the structures score and their clinical weights, is determined. After a necessary
      clinical validation of the group weights, SPIDERplan efficacy, to compare and
      rank different plans, was tested through a planning exercise where plans had been
      generated for a nasal cavity case using different treatment planning systems.
      RESULTS: SPIDERplan method was applied to the dose metrics achieved by the nasal
      cavity test plans. The generated diagrams and scores successfully ranked the
      plans according to the prescribed dose objectives and constraints and the
      radiation oncologist priorities, after a necessary clinical validation process.
      CONCLUSIONS: SPIDERplan enables a fast and consistent evaluation of plan quality
      considering all targets and organs at risk.

PMID- 27698592
TI  - Treatment planning study of Volumetric Modulated Arc Therapy and three
      dimensional field-in-field techniques for left chest-wall cancers with regional
      lymph nodes.
AB  - AIM: This study aims to investigate whether there are dosimetric advantages to
      using VMAT (Volumetric Modulated Arc Therapy) for left-sided chest-wall patients
      over the three-dimensional conformal field-in-field (FinF) technique. BACKGROUND:
      There is a lack of dosimetric studies dedicated for chest-wall patients.
      Potential dosimetric advantage could be obtained using VMAT due to complex
      geometry of PTVs (Planning Target Volumes) and OARs (Organs at Risk) in chest
      wall and lymph nodes. MATERIALS AND METHODS: VMAT and FinF plans were generated
      and evaluated based on DVHs (Dose Volume Histograms) for both PTVs and OARs for
      22 left-sided chest-wall patients with involved regional nodes. PTV HIs
      (Homogeneity Indices) and CIs (Conformity Indices), and EUDs (Equivalent Uniform
      Doses) for PTVs and OARs were also evaluated for comparisons between VMAT and
      FinF. RESULTS: FinF planning met PTV criteria adequately in all cases except two.
      In these two cases, VMAT was able to meet PTV criteria adequately. VMAT
      demonstrated significant reduction in left lung V20 Gy in chest-wall patients
      compared to FinF plans. The volumes of the right lung and right breast receiving
      5 Gy were much higher in VMAT than those in FinF for all patients. CONCLUSIONS:
      Compared to the FinF technique, there is a generally limited benefit using VMAT
      for left-sided chest-wall patients due to large low-dose-bath to OARs with
      insignificant improvement in PTV coverage. In case where FinF planning cannot
      meet dose constrains, VMAT provides a viable option. The use of VMAT planning
      over the FinF technique in chest-wall cancers should be carefully analyzed on an
      individual basis.

PMID- 27698593
TI  - Hypofractionated accelerated radiotherapy in T1-3 N0 cancer of the larynx: A
      prospective cohort study with historical controls.
AB  - AIM: The goal of this prospective study was to assess the effectiveness of a
      hypofractionated accelerated regime in treatment of the larynx cancer.
      BACKGROUND: Multiple radiotherapy delivery regimes are used for treatment of the
      larynx cancer. Hypofractionated regimes could provide similar results with
      reduced use of radiotherapy facilities. MATERIAL AND METHODS: 223 patients with
      squamous cell carcinoma of the upper or middle larynx have been treated with 63
      Gy delivered in 28 fractions of 2.25 Gy during 38 days, 5 fractions per week. The
      study endpoints were overall survival, progression-free survival, early and late
      treatment toxicity. Standard and accelerated radiotherapy groups from the study
      published by Hliniak et al.20 served as controls. RESULTS: Five-year actuarial
      overall survival was 87.5% in the study group, 84.5% in the control group
      receiving accelerated radiotherapy (33 fractions of 2.0 Gy, 6 fractions per week)
      and 86.2% in the control group (33 fractions of 2.0 Gy, 5 fractions per week).
      Five-year progression-free survival was 73.6%, 77.2% and 66.2%, respectively.
      Overall, treatment toxicity and complication rates did not differ between the
      study group and the control groups. CONCLUSIONS: The hypofractionated accelerated
      radiotherapy protocol using 5 fractions per week reduced the use of radiotherapy
      facilities. There was no significant difference in overall survival and
      progression-free survival between the study and control groups treated with
      accelerated or standard radiotherapy.

PMID- 27698594
TI  - THE COMPARING OF ANTIMICROBIAL ACTIVITY OF CSN1S2 PROTEIN OF FRESH MILK AND
      YOGHURT GOAT BREED ETHAWAH INHIBITED THE PATHOGENIC BACTERIA.
AB  - BACKGROUND: Goat milk is reported to have antimicrobial activity of several
      pathogen bacteria that contained on food materials. The research related with
      antimicrobial activity of Alpha-S2 casein from goat milk is relatively less than
      other casein components. Herein, we reported the antimicrobial activity of
      caprine Alpha-S2 Casein (CSN1S2) protein from Ethawah breed goat milk and yoghurt
      in Gram positive (Listeria monocytogenes, Staphylococcus aureus and Bacillus
      cereus) and negative pathogen bacteria (Escherichia coli, Salmonella typhi and
      Shigella flexneri). Those bacteria were known as pathogens that caused
      gastrointestinal infection. METHODS: Serial dilution and agar diffusion analysis
      with three different concentrations of caprine CSN1S2, 1.25 mg/ml, 2.5 mg/ml, and
      5 mg/ml were used to test the inhibition effect of protein on the viability of
      bacteria cells. The inhibitory activity of caprine CSN1S2 was based on dose
      dependent manner. Agar diffusion analysis was showed the larger diameter of clear
      zone at B. cereus and S. flexneri. RESULTS: The serial dilution analysis was
      shown the inhibition of almost in all groups of bacteria with concentration 5
      mg/ml higher by CSN1S2 protein of goat fresh milk than yogurt. The inhibitory
      activity caprine CSN1S2 protein of fresh milk was shown a vary inhibition clear
      zone with optimal concentration 5 mg/ml, however CSN1S2 protein of goat yogurt
      intermediate effectively was only in gram negative bacteria. The weakness
      bacteria against inhibition activity caprine CSN1S2 protein was B. cereus (Gram
      positive) and S. flexneri (Gram negative). Meanwhile the strongest bacteria
      against inhibition activity caprine CSN1S2 protein was S. typhi (Gram negative),
      may cause in this bacteria has lipopolysaccharide prevent to interact with that
      protein as proper. CONCLUSION: This study result concluded that the caprine
      CSN1S2 protein has inhibition activity in opposition to pathogenic bacteria by
      optimal concentration 5 mg/ml in all bacteria and indicated caprine CSN1S2
      protein as anti-microbial agent.

PMID- 27698595
TI  - STUDY OF THE STATUS OF TUBERCULOSIS CONTROL PROGRAM BASED ON THE IMPLEMENTATION
      OF THE DIRECTLY OBSERVED TREATMENT SHORT-COURSE STRATEGY (DOTS).
AB  - INTRODUCTION: Ascendant trend of tuberculosis in the world introduces this
      disease to be one of the most important infectious diseases in the world. So that
      every year, 9 million people are afflicted to active TB and about 5.1 million
      people die of the disease. As the HIV contaminated cases are increased, emergence
      and spread field of Multidrug-resistant tuberculosis (MDR-TB) bacilli has been
      provided. OBJECTIVE: This study aimed to assess the Tuberculosis Control Program
      from 2005 to 2012 to determine the overall situation of disease epidemiology and
      prioritized strategies in disease control program within the south of Tehran.
      MATERIALS AND METHODS: This cross-sectional study was extracted and analyzed
      retrospectively on the basis of records of all TB patients in TB health center
      and TB software in south Tehran in 2005-2012 years. RESULTS: From the total
      population under protection of health center of south Tehran, 99% are urban and
      1% are rural. During 2005-2012, 1242 TB cases have been registered and they were
      treated by DOTS method. There were 553 cases of new smear-positive pulmonary TB
      (44%), 222 cases of smear-negative pulmonary TB (18%) and 336 cases of extra
      pulmonary tuberculosis (27%), 26 cases of recurrence (2%) and 11 cases of MDR
      (0.9%). Smear-positive pulmonary tuberculosis has included 67.4% of all
      tuberculosis patients. CONCLUSIONS: The results showed that, in accordance with
      TB worldwide statistics, at the health center of south Tehran, pulmonary TB is
      the most common form of the disease (67.4%). The incidence of smear-positive
      tuberculosis and all forms of TB cases has been an ascending trend over the
      period between 2005 and 2012.

PMID- 27698596
TI  - INVESTIGATION OF THE EFFECTIVENESS OF ACUPUNCTURE IN THE TREATMENT OF FROZEN
      SHOULDER.
AB  - BACKGROUND: Adhesive capsulitis is a common disease that causes pain and reduced
      range of motion, but vague on the shoulder. Woman are affected fewer than men,
      but there is no known racial or genetic tendency. Most patients with adhesive
      capsulitis will improve with nonsurgical treatment. Acetaminophen and
      nonsteroidal anti-inflammatory drugs for pain relief in patients without
      contraindication are first-line options. Acupuncture considered being safe and
      effective in reducing pain. The aim of this study was to Investigation of the
      effectiveness of acupuncture in the treatment of frozen shoulder. MATERIALS AND
      METHODS: In a controlled clinical trial, patients referred to the Baqiatallah
      clinic in 91 years with shoulder pain, frozen shoulder diagnosed based on history
      and physical exam, they have been enrolled. Indicators measured in the study was
      included the involved joint pain, range of motion and quality of life. Patients,
      first at baseline, one and a half months later (end of session) and then 3 months
      after the examination information about each individual entered in the from of
      questionnaires were pre-determined and data were analyzed by SPSS 17 software.
      RESULTS: In this clinical trial study total 40 patients with frozen shoulder (20
      interference with the acupuncture and 20 people control) study that patients
      average age 55/54. Age maximum 71 years and minimum 44 years. Acupuncture in the
      treatment of frozen shoulder with the results achieved in the general case
      acupuncture may improve shoulder motion in patients. VAS index at three months
      after treatment compared with the control group had a greater improvement.
      CONCLUSION: In the case of acupuncture and ultimately improve the overall look of
      all the movement of flexion and adduction of the shoulder, but the movement has
      been further improved, VAS index at three months after treatment compared with
      the control group had a greater improvement and finally, we perform acupuncture
      as a way to improve shoulder motion in patients with frozen shoulder offered.

PMID- 27698598
TI  - RELATIONSHIP OF ASSESS SELF-ESTEEM AND LOCUS OF CONTROL WITH QUALITY OF LIFE
      DURING TREATMENT STAGES IN PATIENTS REFERRING TO DRUG ADDICTION REHABILITATION
      CENTERS.
AB  - OBJECTIVE: Thus, the present research was carried out aimed at determining the
      relationship between self-esteem and locus of control and quality of life during
      treatment stages in the patients referring to drug addiction rehabilitation
      centers of Borujen city, Iran. METHODS: The current study was a sectional
      research of descriptive correlation type. The research sample was 150 individuals
      of patients referring to addiction rehabilitation centers of Borujen city. For
      data gathering, Rosenberg Self-esteem Scale, Rotter's Locus of Control Scale, and
      SF36 Quality of Life Questionnaire were used. Following collection of
      questionnaires, the data were analyzed using SPSS/16 software. RESULTS: According
      to the results, in the 12th day of treatment, 96 patients exhibited moderate self
      esteem, 102 patients had internal locus of control, and the score of their
      overall quality of life was 40.43+/-12.71. Furthermore, Pearson's correlation
      coefficient indicated that a significant and positive relationship was observed
      between locus of control and quality of life during different treatment stages.
      CONCLUSION: It seems that quality of life improves during addiction treatment
      stages due to improvement of personality traits including locus of control and
      self-esteem. Therefore, consultation methods as a very crucial priority in
      addiction rehabilitation centers shall be taken into account by the health sector
      authorities and managers and can play an essential role in enhancing quality of
      life.

PMID- 27698597
TI  - ADHERENCE AND QUALITY OF LIFE IN PATIENTS WITH TYPE II DIABETES MELLITUS IN
      NORTHERN GREECE.
AB  - INTRODUCTION: Adherence as a concept includes various types of health-related
      behavior. Better medical adherence leads to improved disease control and fewer
      diabetes-related complications. Quality of life and medication adherence are
      interrelated. Patients with diabetes who adhere to their treatment can experience
      an improvement in quality of life and vice versa. AIM: To assess treatment
      adherence in patients with type II diabetes, as well as the connection between
      adherence and quality of life. METHODOLOGY: A descriptive non-experimental study
      was conducted in a provincial hospital in Northern Greece. The sample examined
      was a convenience sample consisting of 108 patients with type II diabetes
      mellitus. They completed the "Diabetes Self-Care Activities Questionnaire" and SF
      36 "Quality of Life Questionnaire". RESULTS: Participants demonstrated good
      adherence to diet and blood test / blood glucose test routines, but did not
      experience high levels of quality of life. The type of treatment affected the
      adherence to blood tests with a statistically significant difference (p=0,000).
      Also, marital status affected mental health with a statistically significant
      difference (p=0,032). The adherence sub scales are correlated with the all
      domains of quality of life. CONCLUSIONS: According to our findings, it is
      important to plan interventions to enhance adherence to other types of treatment
      and to help patients to further improve their quality of life.

PMID- 27698599
TI  - PLATELET COUNT IN WOMEN WITH PREGNANCY INDUCED HYPERTENSION IN UNIVERSITY
      HOSPITAL CENTER OF MOTHER AND CHILD HEALTHCARE "KOcO GLIOZHENI", TIRANA, ALBANIA.
AB  - INTRODUCTION: One of the most common and potential life threatening complications
      of pregnancy is pregnancy induced hypertension. This cross-sectional study aimed
      to investigate the relationship between platelet count and pregnancy induced
      hypertension. MATERIAL AND METHODS: Twenty (20) patients (subjects) and twenty
      (20) healthy pregnant women (control) visiting the Obstetrics and Gynecology
      Hospital University of "Koco Gliozheni" Tirana Albania were registered in the
      study and followed during their pregnancy. Both, subjects and control
      participants were subject to platelet count manually performed using standard
      methods on. RESULTS: The mean platelet count of the control group (38448+/
      235500) was significantly higher than that of the subject group (217050+/
      50780.7) (p<0.03). In the first and second trimester was more prevalent low
      platelet counting with the mean platelet count (107 +/-57.3) and (101 +/-63.4),
      respectively. The mean age at marriage in subjects with PIH was found to be with
      low platelet count. Regular monitoring of platelet counts in women with Pregnancy
      Induced Hypertension must be subject of the management protocols.

PMID- 27698600
TI  - COMPARISON BETWEEN SUBLINGUAL AND VAGINAL ROUTE OF MISOPROSTOL IN MANAGEMENT OF
      FIRST TRIMESTER MISCARRIAGE MISSING.
AB  - BACKGROUND: Each year, more than forty million abortions are occurred whole of
      the world. Misoprostol is a prostaglandin analogue with a strong uterotonic
      effect. The present study aimed to compare the efficacy of Misoprostol in first
      trimester abortion through two sublingual and vaginal routes of administration.
      METHODS: This randomized clinical trial was conducted on 52 consecutive women in
      first trimester candidate for pregnancy termination because of fetal IUFD or
      missed abortion in sonography reports. The patients were hospitalized and then
      randomly assigned to receive sublingual Misoprostol (400 ug, n 27) or vaginal
      Misoprostol (400 ug placed in posterior fornix, n = 25). FINDINGS: None of the
      pregnant in the sublingual group developed complete abortion at the end of follow
      up time, while 36% of women inducted with vaginal misoprostol experienced
      complete abortion indicating a intergroup significant difference (p = 0.001).
      Compared with vaginal group, those women in sublingual group experienced more
      complications including diarrhea (22.2% versus 20.0%), nausea and vomiting (22.2%
      versus 0.0%), and abdominal pain (3.7% versus 0.0%). CONCLUSION: The use of
      Misoprostol in vaginal route results in more abortion completeness as well as
      lower complication rate as compared to sublingual prescription of the drug.

PMID- 27698602
TI  - PARENTS' ATTITUDES ON THE INTRODUCTION OF HEALTH EDUCATION IN THE EDUCATION
      SYSTEM.
AB  - INTRODUCTION: We explored parents' views on the introduction of HE into the
      educational system, as well as differences in the degree of agreement, depending
      on the gender of the respondents, the school which the children attend and
      children's age. PATIENTS AND METHODS: Examinees in this study were parents (N =
      531) of children attending primary and secondary schools in the area of
      Municipality Livno. The study was conducted by using cross-sectional study and a
      special questionnaire was created assessing attitudes on the introduction of HE
      in the education system which contains 26 items. RESULTS: Parents have positively
      disposed towards the introduction of HE in schools (M = 2.85) if it would be
      carried out according to previously anticipated and clearly defined literature (M
      = 3.89), which they should be pre-acquainted with (M = 3.78). They also consider
      that the lecturers should be exclusively health workers (M = 3.50) and certainly
      should cover the topics of the quality of human life (M = 4.07), the prevention
      of addiction (M = 4.03), prevention of bullying (M = 4.14) and the culture of
      social communication (M = 4.15). Surely the content of the lectures should be
      adapted to the age of the child and should be adjusted with the principles and
      values imposed by the religion (M = 3.61). Parents most varied in their views
      when it comes to the introduction of sex education in schools (M = 2.9, SD =
      1.53), however, if the contents would correspond with the age of the child (M =
      3.7). There are no gender differences on the issue of the introduction of HE in
      schools (t = 0.018, DF = 499, p> 0.05), as well as differences between the
      schools (F = 1.937, DF = 5,520, p> 0.05), nor between children of various age
      groups (F = 1.667, DF = 2,523, p> 0.05).

PMID- 27698601
TI  - THE MANAGEMENT OF TRANSFUSION SERVICES, ANALYSIS AND ASSESSMENT.
AB  - INTRODUCTION: The hospital blood bank (HBB) need to timely provide adequate
      amounts of blood and blood products for surgeries. For various surgical programs
      are performed assessments of the average number of blood doses needed for
      surgery. By using two types of requisitions BT/AB (blood type/antibody) and
      BT/AB/MT (blood type/antibody/match test) for pretransfusion immunohaematological
      testing in General Hospital "Prim. Dr. Abdulah Nakas" is achieved more rational
      consumption of blood and blood derivatives and financial savings through reduced
      number of matching tests (MT). GOAL: To determine the total amount of pre
      operative requisitions (BT/AB and BT/AB/MT) for blood and blood products at
      surgical departments of the General Hospital "Prim. Dr. Abdulah Nakas" in the
      period from June 1, 2014 - December 31, 2014 and analyze the consumption/return
      of blood in reserve in relation to the surgical disciplines, the total number of
      savings in MT. Conduct assessments MSBOS (Maximum Surgical Blood Ordering
      Schedule). RESULTS: The total amount of preoperative requisitions for blood and
      blood products in surgical wards was 927 requests from which 623 demands or 67.2%
      is tested by BT/MT, while 304 or 32.8% was tested by BT/AB/MT. Transfused in
      total was 617 units of blood and blood products, 275 units were not transfused.
      Probability of transfusions for surgery was 51.3, the highest in the case of
      surgical intensive care 70.4 and the lowest for the department of general surgery
      37.2%. Assessment of indicators of efficient resource management indicates they
      are the best at the delivery ward 0.89, while a total for surgical wards is 0.69.
      In total for surgery on the average were required 2.1 units of blood. By using
      two types of requisitions for pretransfusion immunohaematological testing (BT/AB
      and CG/AB/MT) is achieved more rational use of MT. In 623 requests for BT/AB only
      61 MT were performed. Average of blood units issued in accordance with these
      requirements is 0.08 and the savings in the number of MT amounts to 562.

PMID- 27698603
TI  - THE EFFECT OF EDUCATIONAL INTERVENTION ON KNOWLEDGE AND SELF-EFFICACY FOR PAIN
      CONTROL IN PATIENTS WITH MULTIPLE SCLEROSIS.
AB  - INTRODUCTION: Multiple Sclerosis (MS) is one of the most common autoimmune
      diseases affecting the central nervous system. The prevalence of it is increasing
      in our country too. The pain from disorders can affect quality of life. Several
      studies have pointed to the improvement of patients through educational
      intervention. This study attempted to evaluate the effectiveness of an
      educational intervention based on raising the awareness and self-efficacy for
      pain control among patients with multiple sclerosis during 2015 under the
      coverage of Isfahan MS Society (IMSS). MATERIALS AND METHODS: This was a quasi
      experimental study involving pre-test, post-test and randomized control group
      conducted on 100 patients with MS referred to the Isfahan MS Society (IMSS). The
      educational intervention group learned the pain management self-care lesson
      during 4 weekly sessions. The data were collected through a self-structured
      questionnaire with adequate validity and reliability, containing demographic
      data, awareness and self-efficacy of pain control. The data were assessed through
      descriptive and analytical tests assisted by SPSS 17. The significant level was
      considered as P<0.05. RESULTS: Concerning the questionnaire, 96% of the items
      were responded. Most participants were women. The frequency distribution of
      demographic variables was not significantly different between the two pre-test
      groups. After the intervention, the mean score of knowledge and efficacy among
      patients in the intervention group was significantly higher than the control
      group (P<0.001). CONCLUSIONS: Educational interventions can improve awareness and
      self-efficacy for pain control among patients with MS. Therefore, such
      interventions can be designed to reduce physical and psychological complications
      following multiple sclerosis.

PMID- 27698604
TI  - MOTHERS' SATISFACTION WITH TREATMENT OPPORTUNITIES FOR THEIR CHILDREN WITH AUTISM
      SPECTRUM DISORDER IN BOSNIA AND HERZEGOVINA.
AB  - AIM: The goal of this study was to examine the general satisfaction of mothers of
      children with autism spectrum disorder (ASD) with treatment opportunities for
      their children in Bosnia and Herzegovina. An additional goal was to assess the
      level of mothers' satisfaction with their own involvement in the creation and
      implementation of Individual Education Plans. METHODS: The sample consisted of 98
      mothers of children with ASD. Mothers answered to questions related to their
      perceived satisfaction with treatment options. RESULTS: The results of this study
      indicated that mothers are generally satisfied with educational opportunities for
      their children (61.2%). However, their satisfaction with involvement in the
      creation and implementation of Individual Education Programs was much lower
      (35.7%). Most comments of the mothers were that the treatment options should be
      more widely available and that the educational programs could be improved.
      CONCLUSIONS: Parents of children with ASD should have more information on the
      treatment options available for their children. More educational opportunities
      need to be offered to children with ASD in Bosnia and Herzegovina.

PMID- 27698605
TI  - THE QUANTITATIVE STUDY OF THE FACULTY MEMBERS PERFORMANCE IN DOCUMENTATION OF THE
      MEDICAL RECORDS IN TEACHING HOSPITALS OF MAZANDARAN UNIVERSITY OF MEDICAL
      SCIENCES.
AB  - INTRODUCTION: Documentation of patients' medical records has been always
      emphasized because medical records are as a means to be applied by patients, all
      medical staff, quality evaluations of health care, lawsuits, medical education
      and, etc. Regarding to this, each of the data elements available in the sheets of
      medical records has their own values. The rate of completion indicates the
      importance of the medical recorders for faculty member. So in this article the
      researcher evaluates the completion of medical records in the teaching hospitals
      of Mazandaran University of Medical Sciences. METHODS AND MATERIALS: This cross-
      sectional study has been conducted to review the patients' medical cases in five
      teaching university hospitals. To collect data, a check list was mode based on
      data element arrangement in four main sheets of admission and discharge, summery,
      patients' history and clinical examination and progress note sheets. Recorded
      data were defined as "Yes" with the value 1, not recorded data were defined as
      "No" with the value 2, and not used data were defined for cases in which the
      mentioned variable had no use with the value Zero. The overall evaluation of the
      rate of documentation was considered as %95 -100 equal to "good", 75-94% equal to
      average and under 75% was considered as "poor". Using the sample volume formula,
      281 cases were randomly stratified reviewed. The data were analyzed by the
      software SPSS version 19 and descriptive statistical scales. RESULTS: The results
      have shown that the overall documentation rate in all the four sheets was 62% and
      in a poor level. There was no big difference in the average documentation among
      the hospital. Among the educational group, the gynecology and infection groups
      are equal to each other and had the highest record average (68%). Within the all
      groups, the highest rate has belonged to the documentation of signatures (91%).
      CONCLUSION: Regarding to the overall assessment that documentation rate was in a
      poor level, more attempt should be made to achieve a better condition. Even if a
      data element of the sheets seems meaningless, unnecessary and duplicated, it
      should not be ignored and skipped. In order to solve such problems, it is
      suggested that medical records sheets and the elements that seem unnecessary,
      should be reviewed in relevant committees.

PMID- 27698606
TI  - BELIEFS ABOUT MEDICINES IN PATIENTS WITH HYPERTENSION: THE INSTRUMENT VALIDITY
      AND RELIABILITY IN IRAN.
AB  - PURPOSE: Despite the importance of patients believes as one of the most important
      predictors of treatment adherence behavior, it is rarely considered in numerous
      studies. Then the current survey was aimed to develop and study the beliefs about
      medicines questionnaire (BMQ) in patients with hypertension. MATERIALS AND
      METHODS: The BMQ developed by Horn and et al. was used in the current study. This
      questionnaire included 18 questions in both public and private beliefs regarding
      drug. Face and content validity of the tool was investigated using expert's
      panel. In final, aforementioned tool was tested in 612 participants. To explore
      structure validity and internal consistency, exploratory and confirmatory factor
      analysis and alpha coefficient was conducted. To evaluate the final validity of
      instrument, the mean score of the beliefs about medicines of patients with
      appropriate medication adherence were compared to patients without medication
      adherence. RESULTS: The mean age of patients was 44.08 +/- 10.38 years. Women
      were 314 of participants. Calculated face validity by the impact score for each
      item indicated that all the items of the questionnaire had the impact score of
      more than 1.5. In total, all items had scored higher than 0.79 by considering 18
      items for content validity. The average of content validity index for the
      questionnaire was 0.93. Load of factors were in the range of 0.51 to 0.79. Four
      items explained % 57 of the total variance. Comparison of all instrument items in
      the two groups showed that patients with good adherence had higher score in 15
      items (% 83 of all items). CONCLUSION: The findings suggested that the BMQ in
      patients with hypertension as a valid and reliable instrument can be used to
      evaluate the patients' medication adherence.

PMID- 27698608
TI  - ARE MACRO AND MICRO ENVIRONMENT AFFECTING MANAGEMENT OF FRESH WATER RESOURCES? A
      CASE FROM IRAN WITH PESTLE ANALYSIS.
AB  - INTRODUCTION: Oil spill in fresh water can affect ecological processes and
      accordingly it can influence human health. Iran, due to having 58.8 % of the
      world oil reserves, is highly vulnerable to water contamination by oil products.
      AIM: The aim of this study was to determine environmental factors affecting the
      management of the oil spill into one of the river in Iran using the PESTLE
      analysis. MATERIAL AND METHODS: This was a qualitative case study conducted in
      2015 on an oil spill incident in Iran and its roots from a disaster management
      approach. Semi-structured interviews were conducted for data collection. Seventy
      managers and staffs with those responsible or involved in oil spill incident
      management were recruited to the study. Qualitative content analysis approach was
      employed for the data analysis. Document analysis was used to collect additional
      information. RESULTS: Findings of the present study indicated that different
      factors affected the management of the event of oil spill onto one of the central
      river and consequently the management of drink water resources. Using this
      analysis, managers can plan for such events and develop scenarios for them to
      have better performance for the future events.

PMID- 27698607
TI  - HYPERHOMOCYSTEINEMIA AND ITS TREATMENT IN PATIENTS WITH PARKINSON'S DISEASE.
AB  - INTRODUCTION: Homocysteine is process-product of methionine demethylation. It has
      proatherogenic, prothrombotic, prooxidative, proapoptotic, osteoporotic,
      neurotoxic, neuroinflamatory, and neurodegenerative effects. Hyperhomocysteinemia
      correlates with C667T MTHFR mutation, decrease of folic acid and vitamin B, as
      well as prolonged use of certain medications. MATERIALS AND METHODS: We measured
      levels of homocysteine in thirty patients (15::15) with "de novo" Parkinson's
      disease, with average age 64.17 +/- 13.19 (28-82) years (Department of Neurology,
      University Clinical Center Tuzla). Normal level of homocysteine for women was
      3.36-20.44 micromole/l and 5.9-16 micromole/l for men. We followed the effects of
      medicament approach (folic acid) every six months for next five years. RESULTS:
      20% of patients with "de novo" Parkinson's disease exhibited
      hyperhomocysteinemia. An average level of homocysteine was 13.85 +/- 5.82
      micromole/l. Differences due to age and homocysteine levels, regardless of sex,
      were not concluded. For the next five years intake of folic acid (periodically, 1
      2 months, 5 mg per day, orally) was effective to normalized levels of
      homocysteine in all. CONCLUSION: Hyperhomocysteinemia is present in every fifth
      patient with "de novo" Parkinson's disease. Folic acid is medication of choice in
      treatment of hyperhomocysteinemia coexisting with Parkinson's disease.

PMID- 27698609
TI  - EPIDEMIOLOGICAL ANALYSIS OF OCULAR MELANOMA IN UNIVERSITY CLINIC CENTER IN TUZLA,
      BOSNIA AND HERZEGOVINA.
AB  - AIM: Melanoma represents a malignant tumour arising from melanocytes. Uveal
      melanoma is the most common primary ocular malignancy among the adult population.
      The aim of the study was to examine epidemiological characteristics of ocular
      melanoma in University Clinic Centre in Tuzla, Bosnia and Herzegovina from
      January 2001 till November 2015. METHODS AND MATERIALS: In this retrospective
      study we used all available medical documentation to investigate the clinical
      findings which included age, gender, tumour size, histopathological features and
      the precise anatomic origin of the ocular melanoma. RESULTS: Over the 14 year
      period of this study, there were 32 patients with microscopically confirmed
      ocular melanoma at the Department of Pathology. All malignant melanoma were uveal
      origin. DISCUSSION AND CONCLUSION: For early detection of the disease, regular
      checkups are necessary, especially in older population. As there is a limited
      number of reports on the epidemiology of malignant tumors of eye and ocular adnex
      in our region, this is very important study. We conclude that this is a first
      study in Bosnia and Herzegovina that document the number of uveal melanomas.

PMID- 27698610
TI  - BOLOGNA MODEL OF MEDICAL EDUCATION-UTOPIA OR REALITY.
AB  - Higher education in Europe and in the Balkan's countries is undergoing major
      reforms. The Bologna Process was a major reform created with the claimed goal of
      providing responses to issues such as the public responsibility for higher
      education and research, higher education governance, the social dimension of
      higher education and research, and the values and roles of higher education and
      research in modern, globalized, and increasingly complex societies with the most
      demanding qualification needs. Changes in the curricula, modernization of
      facilities and their alignment with the programs of other European universities,
      employment of a larger number of assistants, especially in the clinical courses
      at our universities are necessary. Also, it is necessary to continue to conduct
      further detailed analysis and evaluation of teaching content and outcomes in the
      future. In this review authors expressed their views and experience of using
      Bologna model of education in the Balkan's countries with emphasis on Bosnia and
      Herzegovina and the Republic of Macedonia.

PMID- 27698611
TI  - Moving Beyond Readability Metrics for Health-Related Text Simplification.
AB  - Limited health literacy is a barrier to understanding health information.
      Simplifying text can reduce this barrier and possibly other known disparities in
      health. Unfortunately, few tools exist to simplify text with demonstrated impact
      on comprehension. By leveraging modern data sources integrated with natural
      language processing algorithms, we are developing the first semi-automated text
      simplification tool. We present two main contributions. First, we introduce our
      evidence-based development strategy for designing effective text simplification
      software and summarize initial, promising results. Second, we present a new study
      examining existing readability formulas, which are the most commonly used tools
      for text simplification in healthcare. We compare syllable count, the proxy for
      word difficulty used by most readability formulas, with our new metric 'term
      familiarity' and find that syllable count measures how difficult words 'appear'
      to be, but not their actual difficulty. In contrast, term familiarity can be used
      to measure actual difficulty.

PMID- 27698612
TI  - Distinct Ecological Niche of Anal, Oral, and Cervical Mucosal Microbiomes in
      Adolescent Women.
AB  - Human body sites represent ecological niches for microorganisms, each providing
      variations in microbial exposure, nutrient availability, microbial competition,
      and host immunological responses. In this study, we investigated the oral, anal,
      and cervical microbiomes from the same 20 sexually active adolescent females,
      using culture-independent, next-generation sequencing. DNA from each sample was
      amplified for the bacterial 16S rRNA gene and sequenced on an Illumina platform
      using paired-end reads. Across the three anatomical niches, we found significant
      differences in bacterial community composition and diversity. Overall anal
      samples were dominated with Prevotella and Bacteriodes, oral samples with
      Streptococcus and Prevotella, and cervical samples with Lactobacillus. The
      microbiomes of a few cervical samples clustered with anal samples in weighted
      principal coordinate analyses, due in part to a higher proportion of Prevotella
      in those samples. Additionally, cervical samples had the lowest alpha diversity.
      Our results demonstrate the occurrence of distinct microbial communities across
      body sites within the same individual.

PMID- 27698614
TI  - Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic
      Factors.
AB  - The development of the neonatal gut microbiome is influenced by multiple factors,
      such as delivery mode, feeding, medication use, hospital environment, early life
      stress, and genetics. The dysbiosis of gut microbiota persists during infancy,
      especially in high-risk preterm infants who experience lengthy stays in the
      Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is
      essentially parallel with the host (infant) neurodevelopmental process and
      growth. The role of the gut microbiome, the brain-gut signaling system, and its
      interaction with the host genetics have been shown to be related to both short
      and long term infant health and bio-behavioral development. The investigation of
      potential dysbiosis patterns in early childhood is still lacking and few studies
      have addressed this host-microbiome co-developmental process. Further research
      spanning a variety of fields of study is needed to focus on the mechanisms of
      brain-gut-microbiota signaling system and the dynamic host-microbial interaction
      in the regulation of health, stress and development in human newborns.

PMID- 27698616
TI  - Human Microbiota and Ophthalmic Disease.
AB  - The human ocular surface, consisting of the cornea and conjunctiva, is colonized
      by an expansive, diverse microbial community. Molecular-based methods, such as
      16S rRNA sequencing, has allowed for more comprehensive and precise
      identification of the species composition of the ocular surface microbiota
      compared to traditional culture-based methods. Evidence suggests that the normal
      microbiota plays a protective immunological role in preventing the proliferation
      of pathogenic species and thus, alterations in the homeostatic microbiome may be
      linked to ophthalmic pathologies. Further investigation of the ocular surface
      microbiome, as well as the microbiome of other areas of the body such as the oral
      mucosa and gut, and their role in the pathophysiology of diseases is a
      significant, emerging field of research, and may someday enable the development
      of novel probiotic approaches for the treatment and prevention of ophthalmic
      diseases.

PMID- 27698613
TI  - The Influence of the Gut Microbiota on Host Physiology: In Pursuit of Mechanisms.
AB  - The results generated from the NIH funded Human Microbiome Project (HMP) are
      necessarily tied to the overall mission of the agency, which is to foster
      scientific discoveries as a basis for protecting and improving health. The
      investment in the HMP phase 1 accomplished many of its goals including the
      preliminary characterization of the human microbiome and the identification of
      links between microbiome diversity and disease states. Going forward, the next
      step in these studies must involve the identification of the functional molecular
      elements that mediate the positive influence of a eubiotic microbiome on health
      and disease. This review will focus on recent advances describing mechanistic
      events in the intestine elicited by the microbiome. These include symbiotic
      bacteria-induced activation of redox-dependent cell signaling, the bacterial
      production of short chain fatty acids and ensuing cellular responses, and the
      secretion of bacteriocins by bacteria that have anti-microbial activities against
      potential pathogens.

PMID- 27698617
TI  - Unraveling the Dynamics of the Human Vaginal Microbiome.
AB  - Four Lactobacillus species, namely L. crispatus , L. iners, L. gasseri, and L.
      jensenii, commonly dominate the vaginal communities of most reproductive-age
      women. It is unclear why these particular species, and not others, are so
      prevalent. Historically, estrogen-induced glycogen production by the vaginal
      epithelium has been proffered as being key to supporting the proliferation of
      vaginal lactobacilli. However, the 'fly in the ointment' (that has been largely
      ignored) is that the species of Lactobacillus commonly found in the human vagina
      cannot directly metabolize glycogen. It would appear that this riddle has been
      solved as studies have demonstrated that vaginal lactobacilli can metabolize the
      products of glycogen depolymerization by alpha-amylase, and fortunately, amylase
      activity is found in vaginal secretions. These amylases are presumed to be host
      derived, but we suggest that other bacterial populations in vaginal communities
      could also be sources of amylase in addition to (or instead of) the host. Here we
      briefly review what is known about human vaginal bacterial communities and
      discuss how glycogen-derived resources and resource competition might shape the
      composition and structure of these communities.

PMID- 27698615
TI  - Breathing Better Through Bugs: Asthma and the Microbiome.
AB  - Asthma is a highly heterogeneous disease characterized by inflammation of the
      airways, which invokes symptoms such as wheeze, dyspnea, and chest tightness.
      Asthma is the product of multiple interconnected immunological processes and
      represents a constellation of related, but distinct, disease phenotypes. The
      prevalence of asthma has more than doubled since the 1980s, and efforts to
      understand this increase have inspired consideration of the microbiome as a key
      player in the pathophysiology and regulation of this disease. While recent years
      have seen an explosion of new research in this area, researchers are only
      beginning to untangle to mechanisms by which the microbiome may influence asthma.
      This review will focus on the relationship between the microbiome and the immune
      system and how this influences development of asthma. This review will also
      highlight evidence that may point the way toward new therapies and potential
      cures for this ancient respiratory foe.

PMID- 27698618
TI  - An Ecological Framework of the Human Virome Provides Classification of Current
      Knowledge and Identifies Areas of Forthcoming Discovery.
AB  - Recent advances in sequencing technologies have opened the door for the
      classification of the human virome. While taxonomic classification can be applied
      to the viruses identified in such studies, this gives no information as to the
      type of interaction the virus has with the host. As follow-up studies are
      performed to address these questions, the description of these virus-host
      interactions would be greatly enriched by applying a standard set of definitions
      that typify them. This paper describes a framework with which all members of the
      human virome can be classified based on principles of ecology. The scaffold not
      only enables categorization of the human virome, but can also inform research
      aimed at identifying novel virus-host interactions.

PMID- 27698619
TI  - Metagenomic Assembly: Overview, Challenges and Applications.
AB  - Advances in sequencing technologies have led to the increased use of high
      throughput sequencing in characterizing the microbial communities associated with
      our bodies and our environment. Critical to the analysis of the resulting data
      are sequence assembly algorithms able to reconstruct genes and organisms from
      complex mixtures. Metagenomic assembly involves new computational challenges due
      to the specific characteristics of the metagenomic data. In this survey, we focus
      on major algorithmic approaches for genome and metagenome assembly, and discuss
      the new challenges and opportunities afforded by this new field. We also review
      several applications of metagenome assembly in addressing interesting biological
      problems.

PMID- 27698621
TI  - The Impact of the Gut Microbiota on Drug Metabolism and Clinical Outcome.
AB  - The significance of the gut microbiota as a determinant of drug pharmacokinetics
      and accordingly therapeutic response is of increasing importance with the advent
      of modern medicines characterised by low solubility and/or permeability, or
      modified-release. These physicochemical properties and release kinetics prolong
      drug residence times within the gastrointestinal tract, wherein biotransformation
      by commensal microbes can occur. As the evidence base in support of this
      supplementary metabolic "organ" expands, novel opportunities to engineer the
      microbiota for clinical benefit have emerged. This review provides an overview of
      microbe-mediated alteration of drug pharmacokinetics, with particular emphasis on
      studies demonstrating proof of concept in vivo. Additionally, recent advances in
      modulating the microbiota to improve clinical response to therapeutics are
      explored.

PMID- 27698622
TI  - Treating Obesity and Metabolic Syndrome with Fecal Microbiota Transplantation.
AB  - The worldwide prevalence of metabolic syndrome, which includes obesity and its
      associated diseases, is rising rapidly. The human gut microbiome is recognized as
      an independent environmental modulator of host metabolic health and disease.
      Research in animal models has demonstrated that the gut microbiome has the
      functional capacity to induce or relieve metabolic syndrome. One way to modify
      the human gut microbiome is by transplanting fecal matter, which contains an
      abundance of live microorganisms, from a healthy individual to a diseased one in
      the hopes of alleviating illness. Here we review recent evidence suggesting
      efficacy of fecal microbiota transplant (FMT) in animal models and humans for the
      treatment of obesity and its associated metabolic disorders.

PMID- 27698620
TI  - The Hoops, Hopes, and Hypes of Human Microbiome Research.
AB  - Recent developments in sequencing methods and bioinformatics analysis tools have
      greatly enabled the culture-independent analysis of complex microbial communities
      associated with environmental samples, plants, and animals. This has led to a
      spectacular increase in the number of studies on both membership and
      functionalities of these hitherto invisible worlds, in particular those of the
      human microbiome. The wide variety in available microbiome tools and platforms
      can be overwhelming, and making sound conclusions from scientific research can be
      challenging. Here, I will review 1) the methodological and analytic hoops a good
      microbiome study has to jump through, including DNA extraction and choice of
      bioinformatics tools, 2) the hopes this field has generated for diseases such as
      autism and inflammatory bowel diseases, and 3) some of the hypes that it has
      created, e.g., by confusing correlation and causation, and the recent
      pseudoscientific commercialization of microbiome research.

PMID- 27698623
TI  - Striking a Balance with Help from our Little Friends - How the Gut Microbiota
      Contributes to Immune Homeostasis.
AB  - The trillions of microbes that inhabit the human gut (the microbiota) together
      with the host comprise a complex ecosystem, and like any ecosystem, health relies
      on stability and balance. Some of the most important members of the human
      microbiota are those that help maintain this balance via modulation of the host
      immune system. Gut microbes, through both molecular factors (such as capsular
      components) and by-products of their metabolism (such as Short Chain Fatty Acids
      (SCFAs)), can influence both innate and adaptive components of the immune system,
      in ways that can drive both effector, and regulatory responses. Here we review
      how commensal microbes can specifically promote a dynamic balance of these immune
      responses in the mammalian gut.

PMID- 27698624
TI  - Integrative Therapies in Anxiety Treatment with Special Emphasis on the Gut
      Microbiome.
AB  - Over the past decade, research has shown that diet and gut health affects
      symptoms expressed in stress related disorders, depression, and anxiety through
      changes in the gut microbiota. Psycho-behavioral function and somatic health
      interaction have often been ignored in health care with resulting deficits in
      treatment quality and outcomes. While mental health care requires the
      professional training in counseling, psychotherapy and psychiatry, complimentary
      therapeutic strategies, such as attention to a nutritional and diverse diet and
      supplementation of probiotic foods, may be integrated alongside psychotherapy
      treatment models. Development of these alternative strategies is predicated on
      experimental evidence and diligent research on the biology of stress, fear,
      anxiety-related behaviors, and the gut-brain connection. This article provides a
      brief overview on biological markers of anxiety and the expanding nutritional
      literature relating to brain health and mental disorders. A case study
      demonstrates an example of a biopsychosocial approach integrating cognitive
      psychotherapy, dietary changes, and mindfulness activities, in treating symptoms
      of anxiety. This case study shows a possible treatment protocol to explore the
      efficacy of targeting the gut-brain-axis that may be used as an impetus for
      future controlled studies.

PMID- 27698625
TI  - Triggering of Carpal Tunnel Syndrome Symptoms in Patients Using Urban Public
      Transportation.
AB  - Background: Carpal tunnel syndrome (CTS) is the most common compressive
      neuropathy found in clinical practice. Recent studies evaluated which external
      factors could be involved in the CTS symptoms, including prolonged exposure to
      vibration, especially in the upper limb. This study investigated signs and
      symptoms in patients with CTS after using urban transport on (1) both upper
      limbs, (2) how long before these symptoms appear, and (3) the hands position or
      body reaction during the act of pressing the safety bars. Methods: The study was
      conducted from July 2012 to April 2013. A total of 205 (178 women and 27 men)
      patients were evaluated. CTS was diagnosed in 285 hands. All participants
      answered a questionnaire formulated by the authors. The questionnaire was applied
      by researchers who were single-blinded and not involved in the research. Results:
      Most of the participants (87%) were women, but there was no statistical
      significance in age between groups (women = 51.24 +/- 8.47 years, men = 51.10 +/-
      6.52 years, P > .05). The symptoms appeared significantly in the first 15 minutes
      after boarding when compared with patients who had no symptoms during the
      journey. There was no difference between hands position along the journey and the
      onset of symptoms. Conclusions: The onset of symptoms in patients with CTS using
      urban public transportation most commonly occurred in the first 15 minutes after
      boarding. Public transport vibration seems to be, at least in part, directly
      related to the development of symptoms. Questionnaires for the assessment of
      paresthesia symptoms during the use of public transport may be useful for CTS
      diagnosis.

PMID- 27698628
TI  - Hand Surgeon Reporting of Tendon Rupture Following Distal Radius Volar Plating.
AB  - Background: Volar plate fixation with locked screws has become the preferred
      treatment of displaced distal radius fractures that cannot be managed
      nonoperatively. This treatment, however, is not without complication. The purpose
      of this study was to determine what percentage of hand surgeons, over a 12-month
      period, have experienced a tendon complication when using volar plates for the
      treatment of distal radius fractures. Methods: A total of 3022 hand surgeons were
      e-mailed a link to an online questionnaire regarding their observation and
      treatment of tendon injuries associated with volar plating of distal radius
      fractures. Responses were reported using descriptive statistics. Results: Of the
      596 (20%) respondents, 199 (33%) surgeons reported encountering at least one
      flexor tendon injury after distal radius volar plating over the past year of
      practice. The flexor pollicis longus was the most commonly reported tendon injury
      (254, 75%). Palmaris longus grafting (118, 37%) and tendon transfer (114, 36%)
      were the most often reported treatments following this complication. A total of
      216 respondents (36%) also encountered 324 cases of extensor tendon rupture after
      volar plating of distal radius fractures, with tendon transfer (88%) being the
      preferred treatment option. Conclusions: Both flexor and extensor tendon ruptures
      can be seen after volar plating of distal radius fractures. Surgeons should be
      aware of these complications. Critical assessment of hardware position at the
      time of index procedure is recommended to avoid complications. Long-term studies
      are needed to standardize approaches to managing tendon rupture following volar
      plating of distal radius fractures.

PMID- 27698626
TI  - Symbrachydactyly.
AB  - Background: Symbrachydactyly is a unilateral congenital hand malformation
      characterized by failure of formation of fingers and the presence of rudimentary
      digit nubbins. The management is variable and are investigated in this review.
      Methods: A detailed review of the literature was compiled into succinct
      clinically relevant categories. Results: Etiology, classification, non-surgical
      management, surgical intervention, and patient oriented outcomes are discussed.
      Conclusions: All interventions should prioritize realistic, evidence-supported
      appearance and functional gains. Studies of the baseline function and quality of
      life of children with symbrachydactyly would allow surgeons to better understand
      functional changes associated with various interventions and would help surgeons
      and parents to make the best treatment decisions.

PMID- 27698627
TI  - Carpal Coalitions and Metacarpal Synostoses: A Review.
AB  - Background: Carpal coalition and metacarpal synostosis are uncommon congenital
      anomalies of the carpus and hand. Methods: A comprehensive review of the
      literature was performed to help guide surgical and non-surgical treatment of
      carpal coalition and metacarpal synostosis. Results: The embryology,
      epidemiology, medical and surgical management, and associated outcomes are
      detailed. Conclusions: Most patients with these disorders will likely benefit
      from conservative measures. Surgery should be considered in patients with pain
      and limitations in wrist and hand function.

PMID- 27698629
TI  - Malignant Glomus Tumors of the Hand.
AB  - Background: Glomus tumors are uncommon vascular tumors of the hand. Malignant
      glomus tumors, known as glomangiosarcomas, are very rare and offer management
      challenges. Methods: A review of the diagnosis and treatment of malignant glomus
      tumors is presented in along with a report of the largest malignant glomus tumor
      of the hand to date. Results: The review illustrates the management of
      glomangiosarcomas. Only 6 previous such cases have been reported. Conclusion: The
      rare nature of malignant glomus tumors mandates case presentation and
      longitudinal analysis to help guide surgical management an optimize outcomes.

PMID- 27698631
TI  - The Association of Complementary Health Approaches With Mood and Coping
      Strategies Among Orthopedic Patients.
AB  - Background: Variation in pain intensity and magnitude of disability among
      patients with musculoskeletal illness is largely accounted for by variations in
      symptoms of depression, catastrophic thinking, and heightened illness concern. It
      is possible that patients with greater stress, distress, and less effective
      coping strategies might be more likely to seek the use of Complementary Health
      Approaches (CHA). This study addressed the primary null hypothesis that there are
      no demographic, illness-related, or psychological factors associated with CHA use
      among patients with upper extremity illness. Methods: A cohort of 170 patients
      completed a web-based Complementary and Alternative Medicine (CAM) questionnaire
      the Patient Reported Outcomes Measurement Information System (PROMIS) Depression
      and Pain Interference questionnaires. We evaluated differences between patients
      who sought CAM treatment regarding the PROMIS Pain Interference and PROMIS
      Depression scores. Ninety-four patients (56%) use or plan to use CAM treatment. A
      CAM provider was consulted by 61 patients (37%): most commonly a massage
      therapist (30/61), chiropractor (26/61), or acupuncturist (14/61). Results: In
      bivariate analysis patients who sought CAM reported greater average PROMIS Pain
      Interference than those who did not. In multivariable logistic regression, CAM
      use was associated with a higher Pain Interference Score and the specific
      surgeon. Conclusion: In conclusion, CHA use is prevalent amongst orthopaedic
      patients and associated with less effective coping strategies. Orthopaedic
      surgeons might consider asking patients about CHA use and determining whether
      those patients are interested in cognitive behavioral therapy.

PMID- 27698630
TI  - Longitudinal Outcomes Following a Randomized Controlled Trial of Dynamic Splint
      Stretching for Carpal Tunnel Syndrome.
AB  - Background: The incidence of carpal tunnel syndrome (CTS) is 48 million patients
      in the United States. The purpose of this longitudinal study was to determine
      whether Dynasplint stretching (immediately after diagnosis) had an effect on a
      patient's decision to seek surgical treatment for CTS. Methods: Fifty patients
      (10 men, 40 women, mean age 51.2 +/- 12 years) were recruited for this
      randomized, controlled, longitudinal trial. Patients were diagnosed with CTS by
      physical examination and nerve conduction studies. The intervention used was
      Dynasplint stretching that delivered a prolonged duration of low load stretching.
      Patients who were randomly chosen for the Experimental category wore the device
      for two 30-minute sessions per day with regular increases in splint tension for
      60 days. Control patients received nonsteroidal anti-inflammatory medication plus
      instructions on daily home stretching. Results: The final, longitudinal outcome
      showed a 72% reduction in surgery chosen by the experimental group (n = 25),
      compared with 38% reduction for control patients (n = 25). Conclusions: Immediate
      treatment with Dynasplint stretching showed a 2 to 1 reduction in surgery, with
      abundant financial savings.

PMID- 27698633
TI  - Efficient Construction of Volar Wrist Splints: A Biomechanical Study Comparing
      Splints of Different Material, Thickness, and Design.
AB  - Background: The aim was to test the null hypothesis that splint material,
      thickness, or longitudinal ridging does not affect the strength of a wrist
      splint. Methods: Ten splints were made according to each of 7 different splint
      designs (resulting in 7 groups of 10 splints each). All splints were the same
      length and were molded to approximate the contour of the volar hand, wrist, and
      forearm with the wrist in neutral. Three groups consisted of plaster splints of
      different thicknesses (8, 10, and 12 ply). Three additional groups included
      splints of the same thicknesses but with a longitudinal ridge. A single group was
      constructed from prefabricated fiberglass splinting material and did not involve
      a longitudinal ridge. Five splints in each group were subjected to 3-point
      bending mimicking flexion of the wrist and 5 were subjected to a 3-point bend
      mimicking wrist extension. Splints were loaded to failure using a servohydraulic
      load frame. Analysis of variance was used to compare splints. Results: Among the
      plaster splints, more layers of material and longitudinal ridging increased
      splint strength. Ridged 8-ply plaster splints exceeded the strength of nonridged
      10-ply plaster splints. Ridged 8-ply plaster splints were similar in strength to
      fiberglass splints. Conclusions: The 8-ply ridged plaster splints may be a
      lighter, effective, and cheaper alternative to more common splint designs.

PMID- 27698632
TI  - Long-Term Outcomes of Primary Repair of Chronic Thumb Ulnar Collateral Ligament
      Injuries.
AB  - Background: The purpose of this study is to evaluate long-term outcomes of
      ligamentous repair rather than reconstruction for chronic thumb ulnar collateral
      ligament (UCL) injuries. Methods: Patients at least 15-years status-post repair
      of a chronic (greater than 6 weeks) UCL tear were contacted for clinical
      evaluation, radiographs, and postoperative outcome questionnaires, including the
      Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, visual analog
      scale (VAS) pain scale, and study-specific questions. Twelve of 21 (57%) living
      patients were available for long-term, greater than 15-year follow-up (average
      24.5 years, range 16.9-35.6). Results: Eighty-eight percent of patients had some
      degree of osteoarthritis. Increased age at the time of injury and higher DASH
      scores were correlated with increased grades of the thumb metacarpophalangeal
      osteoarthritis. Delay to treatment and VAS pain scores had no correlation with
      radiographic findings. Conclusions: Repair of a chronic UCL injury with available
      local tissue appears to be a reasonable alternative to ligament reconstruction,
      resulting in durable long-term outcomes despite the majority of patients
      progressing to osteoarthritis.

PMID- 27698634
TI  - Linking of the American Academy of Orthopaedic Surgeons Distal Radius Fracture
      Clinical Practice Guidelines to the International Classification of Functioning,
      Disability, and Health; International Classification of Diseases; and ICF Core
      Sets for Hand Conditions.
AB  - Background: American Academy of Orthopaedic Surgeons (AAOS) distal radius
      fracture (DRF) clinical practice guidelines (CPG) are readily available to
      clinicians, patients, and policymakers. International Classification of
      Functioning, Disability, and Health (ICF) provides a framework for describing the
      impact of health conditions. The International Classification of Diseases-10th
      Revision (ICD-10) is a classification system to classify health conditions as
      specific disease or disorders. The aim of this study is to analyze and describe
      the scope and focus of the AAOS DRF CPG using the ICF and ICD-10 as a basis for
      content analysis, and to compare the content of the CPG with the ICF hand core
      sets as the reference standard. Methods: Established linking rules were used by 2
      independent raters to analyze the 29 recommendations of the AAOS DRF CPG. ICD-10
      codes were assigned in the same process. Summary linkage statistics were used to
      describe the results for ICF and the hand core sets. Results: Among the 29
      recommendations of the AAOS DRF CPG, 5 meaningful concepts were linked to the ICF
      codes. Of these, 5 codes appeared on the comprehensive ICF core set and only 3
      codes appeared in the brief ICF core set, and 7 conditions were covered in ICD-10
      codes. Conclusions: The AAOS DRF CPG focuses on surgical interventions and has
      minimal linkage to the constructs of the ICD-10 and ICF. It does not address
      activity or participation (disability), and is not well linked to key concepts
      relevant to hand conditions.

PMID- 27698635
TI  - Distal Inside-Out Epineural Sliding Technique to Repair Segmental Nerve Defects.
AB  - Background: The repair of a segmental peripheral nerve injury is a clinical
      challenge. Several studies have been performed to determine superior methods for
      overcoming nerve gaps. The purpose of this study was to investigate if the inside
      out slided epineurium of the distal segment of an injured nerve can serve as a
      conduit to bridge a short nerve defect (10 mm). Methods: Nineteen sciatic nerves
      in Sprague-Dawley rats were transected, and a 10-mm gap was left between the
      ends. A section of distal epineurium was pulled inside out to bridge the gap.
      Walking track analysis was performed, and the sciatic function index (SFI) was
      calculated. Wet muscle mass and withdrawal reflex were measured. The density of
      axon fibers at different levels of repaired nerves was determined, and
      histological analysis was performed at 16 weeks. Results: The mean SFI improved
      from -81.0 at 4 weeks to 36.3 at 16 weeks. The axon densities showed regeneration
      through the epineural tube, and 5 of the rats demonstrated a withdrawal reflex.
      The weight of the tibialis anterior muscle of the injured limb at 16 weeks was
      59% that of the uninjured side. Conclusions: The distal epineural sheath tube
      provided a size-matched conduit between the nerve stumps, with no histological
      donor-site morbidity. Histologically, regeneration occurred through the epineural
      tube without neuroma formation, and functional recovery was comparable to that of
      previous studies of nerve repair techniques. Technique may be an addition to the
      armamentarium of tools used to treat segmental nerve defects.

PMID- 27698637
TI  - Extensor Indicis Proprius Tenodesis to Correct Finger Ulnar Drift Deformity in
      Rheumatoid Arthritis.
AB  - Background: The most frequent deformity of the hand occurring in patients with RA
      affects the metacarpophalangeal (MCP) joint and it is characterized by a volar
      subluxation of the proximal phalanges and ulnar drift of the fingers. Methods:
      The Extensor Indicis Proprius (EIP) tenodesis for correction of ulnar deviation
      of fingers (II to V) was performed in 10 hands (40 fingers and 5 patients).
      Results: There was complete correction of the subluxation or dislocation and
      almost complete correction of the ulnar drift of the metacarpophalangeal joints
      at the initial postoperative evaluation (three to four months after surgery).
      However, at final evaluation (eight to twelve months after the operation), all of
      the digits had some recurrence of ulnar deviation. Conclusion: The EIP tenodesis
      provides a correct forces vector to maintain the fingers in proper alignment
      following correction of ulnar deviation.

PMID- 27698636
TI  - A Cross-Sectional Study of Musculoskeletal Health Literacy in Patients With
      Carpal Tunnel Syndrome.
AB  - Background: Approximately 33% of Americans have inadequate health literacy, which
      is associated with infrequent use of preventative services, increased
      hospitalization and use of emergency care, and worse control of chronic diseases.
      In this study, the Literacy in Musculoskeletal Problems (LiMP) questionnaire was
      used to evaluate the prevalence of limited musculoskeletal literacy in patients
      undergoing carpal tunnel release (CTR), as these individuals may be at increased
      risk of inferior outcomes. Methods: This cross-sectional study included
      individuals older than or equal to 18 years of age who were scheduled for
      elective CTR. Participants completed a demographic survey and the LiMP
      questionnaire during their preoperative office visit. The prevalence of limited
      health literacy was determined, with chi-square analysis used to determine the
      influence of demographic parameters. Results: The mean LiMP score was 6 +/- 1.40.
      Limited musculoskeletal literacy was seen in 34% of participants (22/65).
      Analysis identified race (Caucasian), gender (female), higher education levels
      (>=college), current or prior employment in a health care field, and a prior
      physician visit for a non-carpal tunnel musculoskeletal complaint as being
      associated with higher literacy rates. Conclusions: Approximately one-third of
      patients scheduled for elective CTR have limited musculoskeletal literacy and may
      lack the necessary skills required for making informed decisions regarding their
      care. This is concerning, as CTR is performed in the United States on roughly 500
      000 individuals annually, at an estimated cost of 2 billion dollars. The
      identification of those most at risk is thus crucial, and will facilitate the
      development of education campaigns and interventions geared toward those who are
      most vulnerable.

PMID- 27698638
TI  - Results of Operative Intervention for Finger Stiffness After Fractures of the
      Hand.
AB  - Background: Posttraumatic finger stiffness can occur as a result of hand
      fractures. The purpose was to assess and quantify the improvement in range of
      motion (ROM) after surgical management of the stiff finger in patients who
      developed loss of motion following treatment for a metacarpal or phalangeal
      fracture. In addition, an aim was to identify possible risk factors for
      suboptimal improvement in ROM postoperatively. Methods: A retrospective review
      was performed on 18 patients who underwent surgery to improve finger stiffness
      following metacarpal or phalangeal fracture. Demographic data including age,
      initial diagnosis and treatment, health history, and worker's compensation status
      were collected. We determined the number of specific procedures performed at the
      time of surgery, the number of days between surgical release and initiation of
      therapy, and the total active motion (TAM) prior to surgical release and at the
      patient's last follow-up. Results: Mean TAM improved from 150 degrees 
      preoperatively (range 60 degrees -241 degrees ) to 191 degrees  postoperatively
      (range 61 degrees -271 degrees ). Most patients required multiple anatomic
      structures released concomitantly, with an average of 3.1. Patients who started
      physical therapy within 7 days of the release improved by 59 degrees , whereas
      those who started physical therapy after 7 days (average 11.5 days) lost 19
      degrees  of motion. Patients who had filed a worker's compensation claim improved
      an average of 9 degrees , whereas nonworker's compensation patients improved an
      average of 58 degrees . Degree of TAM improvement had a weak correlation with
      patient age or preoperative TAM. Conclusions: Surgical release for stiff fingers
      following hand fractures can offer modest improvements in ROM in some patients.
      Although the overall increase in motion as a result of these operations is
      generally limited, functional improvement can be obtained. Delay in initiating
      physical therapy is a risk factor for persistent or worsened stiffness. Patients
      involved in worker's compensation claims demonstrated significantly lower TAM
      improvement after surgical intervention.

PMID- 27698639
TI  - Geographic and Age-Based Variations in Medicare Reimbursement Among ASSH Members.
AB  - Background: The purpose of this study was to investigate how American Society for
      Surgery of the Hand (ASSH) members' Medicare reimbursement depends on their
      geographical location and number of years in practice. Methods: Demographic data
      for surgeons who were active members of the ASSH in 2012 were obtained using
      information publicly available through the US Centers for Medicare and Medicaid
      Services (CMS). "Hand-surgeons-per-capita" and average reimbursement per surgeon
      were calculated for each state. Regression analysis was performed to determine a
      relationship between (1) each state's average reimbursement versus the number of
      ASSH members in that state, (2) average reimbursement versus number of hand
      surgeons per capita, and (3) total reimbursement from Medicare versus number of
      years in practice. Analysis of variance (ANOVA) was used to detect a difference
      in reimbursement based on categorical range of years as an ASSH member. Results:
      A total of 1667 ASSH members satisfied inclusion in this study. Although there
      was significant variation among states' average reimbursement, reimbursement was
      not significantly correlated with the state's hand surgeons per capita or total
      number of hand surgeons in that given state. Correlation between years as an ASSH
      member and average reimbursement was significant but non-linear; the highest
      reimbursements were seen in surgeons who had been ASSH members from 8 to 20
      years. Conclusions: Peak reimbursement from Medicare for ASSH members appears to
      be related to the time of surgeons' peak operative volume, rather than any age
      based bias for or against treating Medicare beneficiaries. In addition, though
      geographic variation in reimbursement does exist, this does not appear to
      correlate with density or availability of hand surgeons.

PMID- 27698640
TI  - Baseline Characteristics of the Median Nerve on Ultrasound Examination.
AB  - Background: Previous studies using ultrasound for diagnosis of carpal tunnel
      syndrome have reported on relatively small series of patients, leading to large
      standard deviations and/or confidence intervals for the mean cross-sectional area
      of the median nerve. The purpose of this study is to define the CSA of the median
      nerve in a large cohort of patients. Methods: Patients (n = 175) without history
      of carpal tunnel release were recruited. All participants were evaluated using
      the Carpal Tunnel Syndrome-6 questionnaire, a validated clinical diagnostic tool,
      with a score of 12 or greater considered positive for CTS. Ultrasound examination
      was performed on both wrists of all participants using a 13-6 MHz linear array
      transducer. Results: The mean median nerve CSA was significantly larger (P <
      .001) for patients with a positive (mean = 11.16, SD = 2.51) versus negative CTS
      6 result (mean = 6.91, SD = 2.06). There was a significant correlation (.527, P <
      .001, n = 349) between CSA and CTS-6 score. Logistic regression analysis
      determined that a CSA of 10 mm2 optimized sensitivity and specificity at 80% and
      88%, respectively. Accuracy was 87.9%. Conclusions: A significant difference in
      mean CSA was found between patients with and without CTS. Median nerve CSA showed
      a statistically significant positive correlation with CTS-6. Similar to prior
      studies, a CSA of 10 mm2 was determined to be the optimal cutoff. In this large
      series of patients, ultrasound was a sensitive, specific, and accurate test for
      confirmation of a clinical diagnosis of CTS.

PMID- 27698642
TI  - Impact of Long Flexor Versus Intrinsic Dominance in the Generation of Arc of
      Finger Flexion.
AB  - Background: Finger flexion is a composite movement involving both long flexors
      and intrinsic hand muscles. Previous studies have characterized this but have not
      investigated differences within the normal population. Were discrete finger
      motion patterns identified, this could guide rehabilitation programs following
      flexor tendon surgery. Methods: Twelve volunteers repeatedly flexed and extended
      at a comfortable speed, resting their hand on a horizontal surface. Video was
      recorded perpendicular to the little finger flexion plane, and the little finger
      tip position was identified frame by frame to create a composite curve. Its
      highest point was noted, and the horizontal distance was measured from this point
      to the palmar digital crease (DeltaXH). Results: In addition, 2 investigators
      independently reviewed frame-by-frame images and allocated subjects into groups
      based on the motion pattern. DeltaXH demonstrated 2 clusters within our study
      population, and there was a statistically significant (P < .036) difference
      between groups. Conclusions: This study demonstrated that qualitative and
      quantitative differences exist in flexion curves between individuals.

PMID- 27698641
TI  - The Radial Artery's Sacrifice in the Chinese Flap Is Not Deleterious to Patients.
AB  - Background: A widely discussed subject, albeit with few associated studies and
      publications, centers on whether sacrifice of the radial artery to perform the
      radial forearm flap (RFF) is deleterious to the patient. The objective of this
      study was to assess, by questionnaire, the complications reported at the donor
      site, particularly those related to sacrifice of the radial artery. Methods:
      During the 2014 Symposium of the Brazilian Society of Reconstructive
      Microsurgery, surgeons were asked to answer a questionnaire on RFF cases and
      complications. Results: Results were collected from hand and plastic surgeons.
      Regarding the opinion of respondents on the deleteriousness of sacrificing the
      radial artery, most answered negatively, that is, no deleterious effects
      reported. No statistically significant difference was found between the level of
      experience and opinion on whether sacrificing the radial artery was deleterious.
      Conclusions: Beyond performing some procedures and following evolution within a
      specific service, it was decided to broaden the range of opinions and enlarge the
      casuistic by assessing the opinions of many specialists from the fields of hand
      surgery and plastic surgery. Data collected using the questionnaire were compared
      to determine the sequelae at the donor site and particularly whether sacrifice of
      the radial artery in RFF was deleterious to the patient. Although complaints at
      the donor site were frequently cited, no objective reports on morbidity following
      the sacrifice of the radial artery in RFF were provided.

PMID- 27698643
TI  - Foreign-Body Reaction and Osteolysis in Dorsal Lunate Dislocation Repair With
      Bioabsorbable Suture Anchor.
AB  - Background: In recent years the use of biodegradable suture anchors for treating
      tendon and ligament pathology in hand surgery became popular. These materials are
      biocompatible, radiolucent, and load sharing, as they incrementally transfer load
      to surrounding bone during the resorption process. Despite these numerous
      advantages, polyglycolic (PGA) and poly-L-lactic acid (PLLA) have become a
      problem because of the potential risk for foreign body reactions. Methods: This
      article presents a case of an intraosseous foreign body reaction and massive
      osteolysis of the proximal carpal after dorsal lunate dislocation repair with
      bioabsorbable suture anchors. Results: Because of the persistent pain and the
      decreased strength, a proximal row carpectomy was performed 12-months after the
      initial trauma. Conclusions: Hand surgeons should be aware of the possibility of
      a late foreign body reaction, that could be especially severe in carpal bones.

PMID- 27698644
TI  - Proximal Interphalangeal Joint Fibromatosis After Pyrocarbon Implant Insertion: A
      Case Report.
AB  - Background: Pyrocarbon implants represent an increasingly popular method to treat
      proximal interphalangeal joint dysfunction. To this point, no association has
      been shown between pyrocarbon biomaterials and fibromatosis. We present a
      potentially serious and destructive complication associated with pyrocarbon
      arthroplasty. Methods: We demonstrate a clinical case involving pyrocarbon
      arthroplasty and subsequent fibromatosis development in an otherwise healthy 23
      year-old female. To present this association, we illustrate the diagnostic workup
      involved in a rapidly expanding soft tissue mass of the hand and explain the
      appropriate treatment. Results: Pyrocarbon arthroplasty was associated with
      development of locally destructive fibromatosis confirmed by histopathological
      examination. Treatment involved wide resection with preservation of local
      structures. Conclusion: We describe the first association between fibromatosis
      and pyrocarbon biomaterial. Due to fibromatosis destructive effects, clinicians
      should be aware of potential complications associated with these materials and
      know how to accurately diagnose and treat these lesions.

PMID- 27698646
TI  - Pleomorphic Hyalinizing Angiectatic Tumor Arising in the Hand: A Case Report.
AB  - Background: Background: Pleomorphic hyalinizing angiectatic tumors (PHATs) are
      extremely rare, non-metastasizing tumors of uncertain origin that are typically
      seen in the lower extremities. To date, it is estimated that less than 100 cases
      have been reported worldwide since first described in 1996. Methods: The case of
      a 35-year-old male with a several-year history of a dorsal hand mass is
      presented. Although the patient was initially asymptomatic, in the months prior
      to presentation, the patient complained of pain with power grasp and direct
      pressure over the mass. The patient underwent uncomplicated surgical excision,
      during which the mass was noted to be adherent to the underlying extensor
      tendons. Results: Immunopathology confirmed the mass to be PHAT. We believe this
      is the first documented case of this rare tumor occurring in the hand.
      Conclusions: History and epidemiology of PHAT are reviewed. Then, in the context
      of the presented case, pre-operative evaluation, surgical management, pathologic
      findings and post-operative follow-up are all discussed.

PMID- 27698645
TI  - Bilateral Legg-Calve-Perthes Disease and Kienbock's Disease in a Child With
      Factor V Leiden Thrombophilia: A Case Report.
AB  - Background: The etiology of multifocal osteonecrosis is not definitively known;
      however, hypercoagulable state is a very plausible cause. Methods: We present an
      unusual case of a 12-year-old boy with a history of Legg-Calve-Perthes disease
      presenting with right wrist pain who was subsequently diagnosed with Kienbock's
      disease. The finding of multifocal osteonecrosis prompted testing for a
      hypercoagulable state that was positive for Factor V Leiden thrombophilia. A
      thorough literature review using Medline database was conducted to investigate
      associations between inherited hypercoagulable states and multifocal
      osteonecrosis. Results: Our literature review identified 2 similar cases of
      multifocal osteonecrosis associated with a hypercoagulable disorder in adult
      patients. There were no reports among the pediatric patient population. Meta
      analysis has demonstrated a potential link between Legg-Calve-Perthes disease and
      Factor V Leiden thrombophilia. Conclusions: This study offers further evidence to
      support the theory that multifocal osteonecrosis may be linked to a
      hypercoagulable state. Patients presenting with multifocal osteonecrosis should
      undergo screening for hypercoagulable states. Further investigation is needed to
      ascertain the potential benefit of prophylactic anticoagulation in patients with
      a known hypercoagulable state and multifocal osteonecrosis.

PMID- 27698647
TI  - Novel FeII and CoII Complexes of Natural Product Tryptanthrin: Synthesis and
      Binding with G-Quadruplex DNA.
AB  - Tryptanthrin is one of the most important members of indoloquinoline alkaloids.
      We obtained this alkaloid from Isatis. Two novel FeII and CoII complexes of
      tryptanthrin were first synthesized. Single-crystal X-ray diffraction analyses
      show that these complexes display distorted four-coordinated tetrahedron geometry
      via two heterocyclic nitrogen and oxygen atoms from tryptanthrin ligand. Binding
      with G-quadruplex DNA properties revealed that both complexes were found to
      exhibit significant interaction with G-quadruplex DNA. This study may potentially
      serve as the basis of future rational design of metal-based drugs from natural
      products that target the G-quadruplex DNA.

PMID- 27698650
TI  - Improved Neural Processing Efficiency in a Chronic Aphasia Patient Following
      Melodic Intonation Therapy: A Neuropsychological and Functional MRI Study.
AB  - Melodic intonation therapy (MIT) is a treatment program for the rehabilitation of
      aphasic patients with speech production disorders. We report a case of severe
      chronic non-fluent aphasia unresponsive to several years of conventional therapy
      that showed a marked improvement following intensive 9-day training on the
      Japanese version of MIT (MIT-J). The purpose of this study was to verify the
      efficacy of MIT-J by functional assessment and examine associated changes in
      neural processing by functional magnetic resonance imaging. MIT improved language
      output and auditory comprehension, and decreased the response time for picture
      naming. Following MIT-J, an area of the right hemisphere was less activated on
      correct naming trials than compared with before training but similarly activated
      on incorrect trials. These results suggest that the aphasic symptoms of our
      patient were improved by increased neural processing efficiency and a concomitant
      decrease in cognitive load.

PMID- 27698648
TI  - Corrigendum: The Associations of Dyadic Coping and Relationship Satisfaction Vary
      between and within Nations: A 35-Nation Study.
AB  - [This corrects the article on p. 1106 in vol. 7, PMID: 27551269.].

PMID- 27698649
TI  - Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala
      in Very Early Alzheimer's Disease.
AB  - Very early Alzheimer's disease (AD) - i.e., AD at stages of mild cognitive
      impairment (MCI) and mild dementia - is characterized by progressive structural
      and neuropathologic changes, such as atrophy or tangle deposition in medial
      temporal lobes, including hippocampus and entorhinal cortex and also adjacent
      amygdala. While progressively disrupted intrinsic connectivity of hippocampus
      with other brain areas has been demonstrated by many studies, amygdala
      connectivity was rarely investigated in AD, notwithstanding its known relevance
      for emotion processing and mood disturbances, which are both important in early
      AD. Intrinsic functional connectivity (iFC) patterns of hippocampus and amygdala
      overlap in healthy persons. Thus, we hypothesized that increased alteration of
      iFC patterns along AD is not limited to the hippocampus but also concerns the
      amygdala, independent from atrophy. To address this hypothesis, we applied
      structural and functional resting-state MRI in healthy controls (CON, n = 33) and
      patients with AD in the stages of MCI (AD-MCI, n = 38) and mild dementia (AD-D, n
      = 36). Outcome measures were voxel-based morphometry (VBM) values and region-of
      interest-based iFC maps of basolateral amygdala, which has extended cortical
      connectivity. Amygdala VBM values were progressively reduced in patients (CON >
      AD-MCI and AD-D). Amygdala iFC was progressively reduced along impairment
      severity (CON > AD-MCI > AD-D), particularly for hippocampus, temporal lobes, and
      fronto-parietal areas. Notably, decreased iFC was independent of amygdala
      atrophy. Results demonstrate progressively impaired amygdala intrinsic
      connectivity in temporal and fronto-parietal lobes independent from increasing
      amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic
      connectivity of medial temporal lobe key regions, including that of amygdala.

PMID- 27698652
TI  - Corrigendum: Biocontrol Ability and Action Mechanism of Starmerella bacillaris
      (Synonym Candida zemplinina) Isolated from Wine Musts against Gray Mold Disease
      Agent Botrytis cinerea on Grape and Their Effects on Alcoholic Fermentation.
AB  - [This corrects the article on p. 1249 in vol. 7, PMID: 27574517.].

PMID- 27698651
TI  - Diffusion Tensor Imaging Findings in Post-Concussion Syndrome Patients after Mild
      Traumatic Brain Injury: A Systematic Review.
AB  - OBJECTIVES: To review the evidence for the use of diffusion tensor imaging (DTI)
      parameters in the human brain as a diagnostic tool for and predictor of post
      concussion syndrome (PCS) after a mild traumatic brain injury (mTBI). DESIGN:
      Systematic review. DATA SOURCES: All relevant studies in AMED, Embase, MEDLINE,
      Ovid, PubMed, Scopus, and Web of Science through 20 May, 2016. STUDY SELECTION:
      Studies that analyze traditional DTI measures [fractional anisotropy (FA), mean
      diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD)] and the
      severity of PCS symptoms or the development of PCS in humans after an mTBI. DATA
      EXTRACTION: Population studied, patient source, mTBI diagnosis method, PCS
      diagnosis method, DTI values measured, significant findings, and correlation
      between DTI findings and PCS. DATA SYNTHESIS: Ten studies investigated
      correlations between DTI values and PCS symptom severity or between DTI values
      and the development of PCS in mTBI patients. Decreased FA and increased MD and RD
      were associated with the development and severity of PCS. AD was not found to
      change significantly. Brain regions found to have significant changes in DTI
      parameters varied from study to study, although the corpus callosum was most
      frequently cited as having abnormal DTI parameters in PCS patients. CONCLUSION:
      DTI abnormalities correlate with PCS incidence and symptom severity, as well as
      indicate an increased risk of developing PCS after mTBI. Abnormal DTI findings
      should prompt investigation of the syndrome to ensure optimal symptom management
      at the earliest stages. Currently, there is no consensus in the literature about
      the use of one DTI parameter in a specific region of the brain as a biomarker for
      PCS because no definite trends for DTI parameters in PCS subjects have been
      identified. Further research is required to establish a standard biomarker for
      PCS.

PMID- 27698653
TI  - Regulatory T Cells Are Dispensable for Tolerance to RBC Antigens.
AB  - Autoimmune hemolytic anemia (AIHA) occurs when pathogenic autoantibodies against
      red blood cell (RBC) antigens are generated. While the basic disease pathology of
      AIHA is well studied, the underlying mechanism(s) behind the failure in tolerance
      to RBC autoantigens are poorly understood. Thus, to investigate the tolerance
      mechanisms required for the establishment and maintenance of tolerance to RBC
      antigens, we developed a novel murine model. With this model, we evaluated the
      role of regulatory T cells (Tregs) in tolerance to RBC-specific antigens. Herein,
      we show that neither sustained depletion of Tregs nor immunization with RBC
      specific proteins in conjunction with Treg depletion led to RBC-specific
      autoantibody generation. Thus, these studies demonstrate that Tregs are not
      required to prevent autoantibodies to RBCs and suggest that other tolerance
      mechanisms are likely involved.

PMID- 27698654
TI  - Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote
      Antigen-Specific Tolerogenic Properties on Naive and Memory CD4+ T Cells.
AB  - Tolerogenic dendritic cells (DCs) are a promising tool to control T cell-mediated
      autoimmunity. Here, we evaluate the ability of dexamethasone-modulated and
      monophosphoryl lipid A (MPLA)-activated DCs [MPLA-tolerogenic DCs (tDCs)] to
      exert immunomodulatory effects on naive and memory CD4+ T cells in an antigen
      specific manner. For this purpose, MPLA-tDCs were loaded with purified protein
      derivative (PPD) as antigen and co-cultured with autologous naive or memory CD4+
      T cells. Lymphocytes were re-challenged with autologous PPD-pulsed mature DCs
      (mDCs), evaluating proliferation and cytokine production by flow cytometry. On
      primed-naive CD4+ T cells, the expression of regulatory T cell markers was
      evaluated and their suppressive ability was assessed in autologous co-cultures
      with CD4+ effector T cells and PPD-pulsed mDCs. We detected that memory CD4+ T
      cells primed by MPLA-tDCs presented reduced proliferation and proinflammatory
      cytokine expression in response to PPD and were refractory to subsequent
      stimulation. Naive CD4+ T cells were instructed by MPLA-tDCs to be hyporesponsive
      to antigen-specific restimulation and to suppress the induction of T helper cell
      type 1 and 17 responses. In conclusion, MPLA-tDCs are able to modulate antigen
      specific responses of both naive and memory CD4+ T cells and might be a promising
      strategy to "turn off" self-reactive CD4+ effector T cells in autoimmunity.

PMID- 27698655
TI  - Neutrophil Integrins and Matrix Ligands and NET Release.
AB  - Neutrophils are motile and responsive to tissue injury and infection. As
      neutrophils emigrate from the bloodstream and migrate toward a site of
      affliction, they encounter the tissue extracellular matrix (ECM) and thereby
      engage integrins. Our laboratory studies the neutrophilic response to the fungal
      pathogen Candida albicans either in the filamentous state of the microbe or to
      the purified pathogen-associated molecular pattern, beta-glucan. We have gained
      an appreciation for the role of integrins in regulating the neutrophil anti
      Candida response and how the presence or absence of ECM can drive experimental
      outcome. The beta2 integrin CR3 (complement receptor 3; alphaMbeta2; Mac-1;
      CD11b/CD18) plays an important role in fungal recognition by its ability to bind
      beta-glucan at a unique lectin-like domain. The presence of ECM differentially
      regulates essential neutrophil anti-fungal functions, including chemotaxis,
      respiratory burst, homotypic aggregation, and the release of neutrophil
      extracellular traps (NETs). We have shown that NET release to C. albicans hyphae
      or immobilized beta-glucan occurs rapidly and without the requirement for
      respiratory burst on ECM. This is in contrast to the more frequently reported
      mechanisms of NETosis to other pathogens without the context of ECM, which occur
      after a prolonged lag period and require respiratory burst. As expected for an
      ECM-dependent phenotype, NETosis and other neutrophil functions are dependent on
      specific integrins. The focus of this review is the role of ECM ligation by
      neutrophil integrins as it pertains to host defense functions with an emphasis on
      lessons we have learned studying the anti-Candida response of human neutrophils.

PMID- 27698658
TI  - An Incremental Radial Basis Function Network Based on Information Granules and
      Its Application.
AB  - This paper is concerned with the design of an Incremental Radial Basis Function
      Network (IRBFN) by combining Linear Regression (LR) and local RBFN for the
      prediction of heating load and cooling load in residential buildings. Here the
      proposed IRBFN is designed by building a collection of information granules
      through Context-based Fuzzy C-Means (CFCM) clustering algorithm that is guided by
      the distribution of error of the linear part of the LR model. After adopting a
      construct of a LR as global model, refine it through local RBFN that captures
      remaining and more localized nonlinearities of the system to be considered. The
      experiments are performed on the estimation of energy performance of 768 diverse
      residential buildings. The experimental results revealed that the proposed IRBFN
      showed good performance in comparison to LR, the standard RBFN, RBFN with
      information granules, and Linguistic Model (LM).

PMID- 27698656
TI  - Neutrophil Extracellular Traps Go Viral.
AB  - Neutrophils are the most numerous immune cells. Their importance as the first
      line of defense against bacterial and fungal pathogens is well described. In
      contrast, the role of neutrophils in controlling viral infections is less clear.
      Bacterial and fungal pathogens can stimulate neutrophils extracellular traps
      (NETs) in a process called NETosis. Although NETosis has previously been
      described as a special form of programmed cell death, there are forms of NET
      production that do not end with the demise of neutrophils. As an end result of
      NETosis, genomic DNA complexed with microbicidal proteins is expelled from
      neutrophils. These structures can kill pathogens or at least prevent their local
      spread within host tissue. On the other hand, disproportionate NET formation can
      cause local or systemic damage. Only recently, it was recognized that viruses can
      also induce NETosis. In this review, we discuss the mechanisms by which NETs are
      produced in the context of viral infection and how this may contribute to both
      antiviral immunity and immunopathology. Finally, we shed light on viral immune
      evasion mechanisms targeting NETs.

PMID- 27698659
TI  - Fracture Mechanics Method for Word Embedding Generation of Neural Probabilistic
      Linguistic Model.
AB  - Word embedding, a lexical vector representation generated via the neural
      linguistic model (NLM), is empirically demonstrated to be appropriate for
      improvement of the performance of traditional language model. However, the
      supreme dimensionality that is inherent in NLM contributes to the problems of
      hyperparameters and long-time training in modeling. Here, we propose a force
      directed method to improve such problems for simplifying the generation of word
      embedding. In this framework, each word is assumed as a point in the real world;
      thus it can approximately simulate the physical movement following certain
      mechanics. To simulate the variation of meaning in phrases, we use the fracture
      mechanics to do the formation and breakdown of meaning combined by a 2-gram word
      group. With the experiments on the natural linguistic tasks of part-of-speech
      tagging, named entity recognition and semantic role labeling, the result
      demonstrated that the 2-dimensional word embedding can rival the word embeddings
      generated by classic NLMs, in terms of accuracy, recall, and text visualization.

PMID- 27698657
TI  - PPARgamma as a Novel Therapeutic Target in Lung Cancer.
AB  - Lung cancer is the leading cause of cancer-related death, with more than half the
      patients having advanced-stage disease at the time of initial diagnosis and thus
      facing a poor prognosis. This dire situation poses a need for new approaches in
      prevention and treatment. Peroxisome proliferator-activated receptor gamma
      (PPARgamma) is a ligand-activated transcription factor belonging to the nuclear
      hormone receptor superfamily. Its involvement in adipocyte differentiation and
      glucose and lipid homeostasis is well-recognized, but accumulating evidence now
      suggests that PPARgamma may also function as a tumor suppressor, inhibiting
      development of primary tumors and metastases in lung cancer and other
      malignancies. Besides having prodifferentiation, antiproliferative, and
      proapoptotic effects, PPARgamma agonists have been shown to prevent cancer cells
      from acquiring the migratory and invasive capabilities essential for successful
      metastasis. Angiogenesis and secretion of certain matrix metalloproteinases and
      extracellular matrix proteins within the tumor microenvironment are also
      regulated by PPARgamma. This review of the current literature highlights the
      potential of PPARgamma agonists as novel therapeutic modalities in lung cancer,
      either as monotherapy or in combination with standard cytotoxic chemotherapy.

PMID- 27698660
TI  - The Brainarium: An Interactive Immersive Tool for Brain Education, Art, and
      Neurotherapy.
AB  - Recent theoretical and technological advances in neuroimaging techniques now
      allow brain electrical activity to be recorded using affordable and user-friendly
      equipment for nonscientist end-users. An increasing number of educators and
      artists have begun using electroencephalogram (EEG) to control multimedia and
      live artistic contents. In this paper, we introduce a new concept based on brain
      computer interface (BCI) technologies: the Brainarium. The Brainarium is a new
      pedagogical and artistic tool, which can deliver and illustrate scientific
      knowledge, as well as a new framework for scientific exploration. The Brainarium
      consists of a portable planetarium device that is being used as brain metaphor.
      This is done by projecting multimedia content on the planetarium dome and
      displaying EEG data recorded from a subject in real time using Brain Machine
      Interface (BMI) technologies. The system has been demonstrated through several
      performances involving an interaction between the subject controlling the BMI, a
      musician, and the audience during series of exhibitions and workshops in schools.
      We report here feedback from 134 participants who filled questionnaires to rate
      their experiences. Our results show improved subjective learning compared to
      conventional methods, improved entertainment value, improved absorption into the
      material being presented, and little discomfort.

PMID- 27698661
TI  - A Forecasting Model for Feed Grain Demand Based on Combined Dynamic Model.
AB  - In order to improve the long-term prediction accuracy of feed grain demand, a
      dynamic forecast model of long-term feed grain demand is realized with joint
      multivariate regression model, of which the correlation between the feed grain
      demand and its influence factors is analyzed firstly; then the change trend of
      various factors that affect the feed grain demand is predicted by using ARIMA
      model. The simulation results show that the accuracy of proposed combined dynamic
      forecasting model is obviously higher than that of the grey system model. Thus,
      it indicates that the proposed algorithm is effective.

PMID- 27698662
TI  - A Novel Hybrid Clonal Selection Algorithm with Combinatorial Recombination and
      Modified Hypermutation Operators for Global Optimization.
AB  - Artificial immune system is one of the most recently introduced intelligence
      methods which was inspired by biological immune system. Most immune system
      inspired algorithms are based on the clonal selection principle, known as clonal
      selection algorithms (CSAs). When coping with complex optimization problems with
      the characteristics of multimodality, high dimension, rotation, and composition,
      the traditional CSAs often suffer from the premature convergence and unsatisfied
      accuracy. To address these concerning issues, a recombination operator inspired
      by the biological combinatorial recombination is proposed at first. The
      recombination operator could generate the promising candidate solution to enhance
      search ability of the CSA by fusing the information from random chosen parents.
      Furthermore, a modified hypermutation operator is introduced to construct more
      promising and efficient candidate solutions. A set of 16 common used benchmark
      functions are adopted to test the effectiveness and efficiency of the
      recombination and hypermutation operators. The comparisons with classic CSA, CSA
      with recombination operator (RCSA), and CSA with recombination and modified
      hypermutation operator (RHCSA) demonstrate that the proposed algorithm
      significantly improves the performance of classic CSA. Moreover, comparison with
      the state-of-the-art algorithms shows that the proposed algorithm is quite
      competitive.

PMID- 27698663
TI  - Fault Diagnosis for Analog Circuits by Using EEMD, Relative Entropy, and ELM.
AB  - This paper presents a novel fault diagnosis method for analog circuits using
      ensemble empirical mode decomposition (EEMD), relative entropy, and extreme
      learning machine (ELM). First, nominal and faulty response waveforms of a circuit
      are measured, respectively, and then are decomposed into intrinsic mode functions
      (IMFs) with the EEMD method. Second, through comparing the nominal IMFs with the
      faulty IMFs, kurtosis and relative entropy are calculated for each IMF. Next, a
      feature vector is obtained for each faulty circuit. Finally, an ELM classifier is
      trained with these feature vectors for fault diagnosis. Via validating with two
      benchmark circuits, results show that the proposed method is applicable for
      analog fault diagnosis with acceptable levels of accuracy and time cost.

PMID- 27698664
TI  - Colon Capsule Endoscopy: Review and Perspectives.
AB  - Colon capsule endoscopy utilizing PillCam COLON 2 capsule allows for
      visualization potentially of the entire colon and is currently approved for
      patients who cannot withstand the rigors of traditional optical colonoscopy (OC)
      and associated sedation as well as those that had an OC that was incomplete for
      technical reasons other than a poor preparation. We will then describe the prior
      experience and current status of colon capsule endoscopy.

PMID- 27698665
TI  - Evaluation and Verification of the Global Rapid Identification of Threats System
      for Infectious Diseases in Textual Data Sources.
AB  - The Global Rapid Identification of Threats System (GRITS) is a biosurveillance
      application that enables infectious disease analysts to monitor nontraditional
      information sources (e.g., social media, online news outlets, ProMED-mail
      reports, and blogs) for infectious disease threats. GRITS analyzes these textual
      data sources by identifying, extracting, and succinctly visualizing epidemiologic
      information and suggests potentially associated infectious diseases. This
      manuscript evaluates and verifies the diagnoses that GRITS performs and discusses
      novel aspects of the software package. Via GRITS' web interface, infectious
      disease analysts can examine dynamic visualizations of GRITS' analyses and
      explore historical infectious disease emergence events. The GRITS API can be used
      to continuously analyze information feeds, and the API enables GRITS technology
      to be easily incorporated into other biosurveillance systems. GRITS is a flexible
      tool that can be modified to conduct sophisticated medical report triaging,
      expanded to include customized alert systems, and tailored to address other
      biosurveillance needs.

PMID- 27698666
TI  - In Silico Analysis of Gene Expression Network Components Underlying Pigmentation
      Phenotypes in the Python Identified Evolutionarily Conserved Clusters of
      Transcription Factor Binding Sites.
AB  - Color variation provides the opportunity to investigate the genetic basis of
      evolution and selection. Reptiles are less studied than mammals. Comparative
      genomics approaches allow for knowledge gained in one species to be leveraged for
      use in another species. We describe a comparative vertebrate analysis of
      conserved regulatory modules in pythons aimed at assessing bioinformatics
      evidence that transcription factors important in mammalian pigmentation
      phenotypes may also be important in python pigmentation phenotypes. We identified
      23 python orthologs of mammalian genes associated with variation in coat color
      phenotypes for which we assessed the extent of pairwise protein sequence identity
      between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter
      snake. We next identified a set of melanocyte/pigment associated transcription
      factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively
      conserved sequence similarity within their DNA binding regions across species
      based on orthologous alignments across multiple species. Finally, we identified
      27 evolutionarily conserved clusters of transcription factor binding sites within
      ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT,
      MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results
      provide insight into pigment phenotypes in pythons.

PMID- 27698667
TI  - Myo-Inositol Safety in Pregnancy: From Preimplantation Development to Newborn
      Animals.
AB  - Myo-inositol (myo-Ins) has a physiological role in mammalian gametogenesis and
      embryonic development and a positive clinical impact on human medically assisted
      reproduction. We have previously shown that mouse embryo exposure to myo-Ins
      through preimplantation development in vitro increases proliferation activity and
      blastocyst production, representing an improvement in culture conditions. We have
      herein investigated biochemical mechanisms elicited by myo-Ins in preimplantation
      embryos and evaluated myo-Ins effects on postimplantation/postnatal development.
      To this end naturally fertilized embryos were cultured in vitro to blastocyst in
      the presence or absence of myo-Ins and analyzed for activation of the PKB/Akt
      pathway, known to modulate proliferation/survival cellular processes. In
      parallel, blastocyst-stage embryos were transferred into pseudopregnant females
      and allowed to develop to term and until weaning. Results obtained provide
      evidence that myo-Ins induces cellular pathways involving Akt and show that (a)
      exposure of preimplantation embryos to myo-Ins increases the number of
      blastocysts available for uterine transfer and of delivered animals and (b) the
      developmental patterns of mice obtained from embryos cultured in the presence or
      absence of myo-Ins, up to three weeks of age, overlap. These data further
      identify myo-Ins as a possibly important supplement for human preimplantation
      embryo culture in assisted reproduction technology.

PMID- 27698669
TI  - A Case of Malignant Biliary Obstruction with Severe Obesity Successfully Treated
      by Endoscopic Ultrasonography-Guided Biliary Drainage.
AB  - Here, we present a case of malignant biliary tract obstruction with severe
      obesity, which was successfully treated by endoscopic ultrasonography-guided
      biliary drainage (EUS-BD). A female patient in her sixties who had been
      undergoing chemotherapy for unresectable pancreatic head cancer was admitted to
      our institution for obstructive jaundice. She had diabetes mellitus, and her body
      mass index was 35.1 kg/m2. Initially, endoscopic retrograde
      cholangiopancreatography (ERCP) was performed, but bile duct cannulation was
      unsuccessful. Percutaneous transhepatic biliary drainage (PTBD) from the left
      hepatic biliary tree also failed. Although a second PTBD attempt from the right
      hepatic lobe was accomplished, biliary tract bleeding followed, and the catheter
      was dislodged. Consequently, EUS-BD (choledochoduodenostomy), followed by direct
      metallic stent placement, was performed as a third drainage method. Her
      postprocedural course was uneventful. Following discharge, she spent the rest of
      her life at home without recurrent jaundice or readmission. In cases of severe
      obesity, we consider EUS-BD, rather than PTBD, as the second drainage method of
      choice for distal malignant biliary obstruction when ERCP fails.

PMID- 27698668
TI  - Radioactive Merano SPA Treatment for Allergic Rhinitis Therapy.
AB  - Allergic rhinitis is a common nasal disorder with a high impact on quality of
      life, high social costs in therapies, and a natural development towards asthma.
      Pharmacological therapy is based on several genres of medications, of which
      intranasal corticosteroids are currently the most widespread. Thermal water
      treatment has traditionally been used as adjunctive treatment for chronic
      rhinitis and sinusitis. The present study was carried out to assess the clinical
      efficacy of nasal inhalation of radioactive oligomineral water vapours from the
      Merano hot spring and to compare it with the clinical efficacy of mometasone
      furoate nasal spray. A comparative prospective study was performed in 90 allergic
      patients treated at Merano hot springs: a group of 54 subjects treated with
      radioactive thermal oligomineral water and a control group of 36 subjects treated
      with mometasone nasal spray. Patients of both groups were assessed before and
      after treatment by Sino-Nasal Outcome Test questionnaire, active anterior
      rhinomanometry with flow and resistance monitoring, measurement of mucociliary
      transport time, and cytological examination of nasal brushing/scraping. The study
      showed that inhalation treatment with radioactive hydrofluoric thermal water for
      two weeks produces an objective clinical and cytological improvement in allergic
      patients, similar to that obtained with mometasone furoate nasal spray.

PMID- 27698670
TI  - A Giant Renal Vein Aneurysm in a Patient with Liver Cirrhosis.
AB  - We present an unusual case of a 40-year-old female patient with liver cirrhosis
      and diffuse abdominal pain. The imaging studies revealed a huge renal vein
      aneurysm. The patient refused any interventional management, despite the risk of
      possible rupture, and after a week of mild pain therapy, she was discharged. She
      was followed up closely, and after one year, she remains asymptomatic.
      Conservative management of such patients has been described before with success.
      However, open repair or percutaneous thrombosis of the aneurysm remains the
      indicated therapy, when vein patency is an issue for organ viability.

PMID- 27698672
TI  - Adipose-Derived Cells (Stromal Vascular Fraction) Transplanted for Orthopedical
      or Neurological Purposes: Are They Safe Enough?
AB  - Although mesenchymal stem cells are used in numerous clinical trials, the safety
      of their application is still a matter of concern. We have analysed the clinical
      results of the autologous adipose-derived stem cell treatment (stromal vascular
      fraction (SVF) containing adipose-derived stem cells, endothelial progenitors,
      and blood mononuclear cells) for orthopedic (cartilage, bone, tendon, or combined
      joint injuries) and neurologic (multiple sclerosis) diseases. Methods of adipose
      tissue collection, cell isolation and purification, and resulting cell numbers,
      viability, and morphology were considered, and patient's age, sex, disease type,
      and method of cell administration (cell numbers per single application, treatment
      numbers and frequency, and methods of cell implantation) were analysed and
      searched for the unwanted clinical effects. Results of cellular therapy were
      compared retrospectively to those obtained with conventional medication without
      SVF application. SVF transplantation was always the accessory treatment of
      patients receiving "standard routine" therapies of their diseases. Clinical
      experiments were approved by the Bioethical Medical Committees supervising the
      centers where patients were hospitalised. The conclusion of the study is that
      none of the treated patients developed any serious adverse event, and autologous
      mesenchymal stem (stromal) cell clinical application is a safe procedure
      resulting in some beneficial clinical effects (not analysed in this study).

PMID- 27698671
TI  - Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies
      for Intracerebral Hemorrhage.
AB  - Stroke is the second leading cause of mortality worldwide, causing millions of
      deaths annually, and is also a major cause of disability-adjusted life years.
      Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a
      fatality rate of about 50% in the first 30 days, with limited treatment
      possibilities. In the past two decades, the therapeutic potential of bone marrow
      derived cells (particularly mesenchymal stem cells and mononuclear cells) has
      been intensively investigated in preclinical models of different neurological
      diseases, including models of intracerebral hemorrhage and subarachnoid
      hemorrhage. More recently, clinical studies, most of them small, unblinded, and
      nonrandomized, have suggested that the therapy with bone marrow-derived cells is
      safe and feasible in patients with ischemic or hemorrhagic stroke. This review
      discusses the available evidence on the use of bone marrow-derived cells to treat
      hemorrhagic strokes. Distinctive properties of animal studies are analyzed,
      including study design, cell dose, administration route, therapeutic time window,
      and possible mechanisms of action. Furthermore, clinical trials are also reviewed
      and discussed, with the objective of improving future studies in the field.

PMID- 27698673
TI  - Suboptimal Clinical Documentation in Young Children with Severe Obesity at
      Tertiary Care Centers.
AB  - Background and Objectives. The prevalence of severe obesity in children has
      doubled in the past decade. The objective of this study is to identify the
      clinical documentation of obesity in young children with a BMI >= 99th percentile
      at two large tertiary care pediatric hospitals. Methods. We used a standardized
      algorithm utilizing data from electronic health records to identify children with
      severe early onset obesity (BMI >= 99th percentile at age <6 years). We extracted
      descriptive terms and ICD-9 codes to evaluate documentation of obesity at Boston
      Children's Hospital and Cincinnati Children's Hospital and Medical Center between
      2007 and 2014. Results. A total of 9887 visit records of 2588 children with
      severe early onset obesity were identified. Based on predefined criteria for
      documentation of obesity, 21.5% of children (13.5% of visits) had positive
      documentation, which varied by institution. Documentation in children first seen
      under 2 years of age was lower than in older children (15% versus 26%).
      Documentation was significantly higher in girls (29% versus 17%, p < 0.001),
      African American children (27% versus 19% in whites, p < 0.001), and the obesity
      focused specialty clinics (70% versus 15% in primary care and 9% in other
      subspecialty clinics, p < 0.001). Conclusions. There is significant opportunity
      for improvement in documentation of obesity in young children, even years after
      the 2007 AAP guidelines for management of obesity.

PMID- 27698675
TI  - Jin Fu Kang Oral Liquid Inhibits Lymphatic Endothelial Cells Formation and
      Migration.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. Jin Fu Kang
      (JFK), an oral liquid prescription of Chinese herbal drugs, has been clinically
      available for the treatment of non-small cell lung cancer (NSCLC).
      Lymphangiogenesis is a primary event in the process of cancer development and
      metastasis, and the formation and migration of lymphatic endothelial cells (LECs)
      play a key role in the lymphangiogenesis. To assess the activity of stromal cell
      derived factor-1 (SDF-1) and the coeffect of SDF-1 and vascular endothelial
      growth factor-C (VEGF-C) on the formation and migration of LECs and clarify the
      inhibitory effects of JFK on the LECs, the LECs were differentiated from
      CD34+/VEGFR-3+ endothelial progenitor cells (EPCs), and JFK-containing serums
      were prepared from rats. SDF-1 and VEGF-C both induced the differentiation of
      CD34+/VEGFR-3+ EPCs towards LECs and enhanced the LECs migration. Couse of SDF-1
      and VEGF-C displayed an additive effect on the LECs formation but not on their
      migration. JFK inhibited the formation and migration of LECs, and the inhibitory
      effects were most probably via regulation of the SDF-1/CXCR4 and VEGF-C/VEGFR-3
      axes. The current finding suggested that JFK might inhibit NSCLC through
      antilymphangiogenesis and also provided a potential to discover
      antilymphangiogenesis agents from natural resources.

PMID- 27698674
TI  - Diabetic Osteoporosis: A Review of Its Traditional Chinese Medicinal Use and
      Clinical and Preclinical Research.
AB  - Aim. The incidence of diabetic osteoporosis (DOP) is increasing due to lack of
      effective management over the past few decades. This review aims to summarize
      traditional Chinese medicine (TCM) suitability in the pathogenesis and clinical
      and preclinical management of DOP. Methods. Literature sources used were from
      Medline (Pubmed), CNKI (China Knowledge Resource Integrated Database), and CSTJ
      (China Science and Technology Journal Database) online databases. For the
      consultation, keywords such as diabetic osteoporosis (DOP), TCM, clinical study,
      animal experiment, toxicity, and research progress were used in various
      combinations. Around 100 research papers and reviews were visited. Results. Liver
      spleen-kidney insufficiency may result in development of DOP. 18 clinical trials
      are identified to use TCM compound prescriptions for management of patients with
      DOP. TCM herbs and their active ingredients are effective in preventing the
      development of DOP in streptozotocin (STZ) and alloxan as well as STZ combined
      with ovariectomy insulted rats. Among them, most frequently used TCM herbs in
      clinical trials are Radix Astragali, Radix et Rhizoma Salviae Miltiorrhizae,
      Radix Rehmanniae Preparata, and Herba Epimedii. Some of TCM herbs also exhibit
      toxicities in clinical and preclinical research. Conclusions. TCM herbs may act
      as the novel sources of anti-DOP drugs by improving bone and glucolipid
      metabolisms. However, the pathogenesis of DOP and the material base of TCM herbs
      still merit further study.

PMID- 27698676
TI  - Hyeonggaeyeongyo-Tang for Treatment of Allergic and Nonallergic Rhinitis: A
      Prospective, Nonrandomized, Pre-Post Study.
AB  - Hyeonggaeyeongyo-tang (HYT) is an ancient formula of oriental medicine
      traditionally used to treat rhinitis; however, clinical evidence has not yet been
      established. The aim of this study was to investigate the short-term and long
      term efficacy and safety of HYT for chronic rhinitis. Adult subjects with chronic
      rhinitis symptoms were recruited. The subjects received HYT for 4 weeks and had
      follow-up period of 8 weeks. Any medicines used to treat nasal symptoms were not
      permitted during the study. The skin prick test was performed to distinguish the
      subjects with allergic rhinitis from those with nonallergic rhinitis. After
      treatment, the total nasal symptoms score and the Rhinoconjunctivitis Quality of
      Life Questionnaire score significantly improved in the whole subject group, in
      the allergic rhinitis group, and in the nonallergic rhinitis group, with no
      adverse events. This improvement lasted during a follow-up period of 8 weeks.
      Total IgE and eosinophil levels showed no significant difference after treatment
      in the allergic rhinitis group. HYT improved nasal symptoms and quality of life
      in patients with allergic rhinitis and nonallergic rhinitis. This is the first
      clinical study to evaluate the use of HYT to treat patients with rhinitis. This
      trial has been registered with the ClinicalTrials.gov Identifier NCT02477293.

PMID- 27698678
TI  - Exploring the Unexplored: Identifying Implicit and Indirect Descriptions of
      Biomedical Terminologies Based on Multifaceted Weighting Combinations.
AB  - In order to achieve relevant scholarly information from the biomedical databases,
      researchers generally use technical terms as queries such as proteins, genes,
      diseases, and other biomedical descriptors. However, the technical terms have
      limits as query terms because there are so many indirect and conceptual
      expressions denoting them in scientific literatures. Combinatorial weighting
      schemes are proposed as an initial approach to this problem, which utilize
      various indexing and weighting methods and their combinations. In the experiments
      based on the proposed system and previously constructed evaluation collection,
      this approach showed promising results in that one could continually locate new
      relevant expressions by combining the proposed weighting schemes. Furthermore, it
      could be ascertained that the most outperforming binary combinations of the
      weighting schemes, showing the inherent traits of the weighting schemes, could be
      complementary to each other and it is possible to find hidden relevant documents
      based on the proposed methods.

PMID- 27698677
TI  - Identification of the Metabolic Enzyme Involved Morusin Metabolism and
      Characterization of Its Metabolites by Ultraperformance Liquid Chromatography
      Quadrupole Time-of-Flight Mass Spectrometry (UPLC/Q-TOF-MS/MS).
AB  - Morusin, the important active component of a traditional Chinese medicine, Morus
      alba L., has been shown to exhibit many vital pharmacological activities. In this
      study, six recombinant CYP450 supersomes and liver microsomes were used to
      perform metabolic studies. Chemical inhibition studies and screening assays with
      recombinant human cytochrome P450s were also used to characterize the CYP450
      isoforms involved in morusin metabolism. The morusin metabolites identified
      varied greatly among different species. Eight metabolites of morusin were
      detected in the liver microsomes from pigs (PLMs), rats (RLMs), and monkeys
      (MLMs) by LC-MS/MS and six metabolites were detected in the liver microsomes from
      humans (HLMs), rabbits (RAMs), and dogs (DLMs). Four metabolites (M1, M2, M5, and
      M7) were found in all species and hydroxylation was the major metabolic
      transformation. CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, and CYP2C19 contributed
      differently to the metabolism of morusin. Compared to other CYP450 isoforms,
      CYP3A4 played the most significant role in the metabolism of morusin in human
      liver microsomes. These results are significant to better understand the
      metabolic behaviors of morusin among various species.

PMID- 27698679
TI  - Huntington's disease: Molecular basis of pathology and status of current
      therapeutic approaches.
AB  - Huntington's disease (HD) is a frequent and incurable hereditary
      neurodegenerative disorder that impairs motor and cognitive functions. Mutations
      in huntingtin (HTT) protein, which is essential for neuronal development, lead to
      the development of HD. An increase in the number of CAG repeats within the HTT
      gene, which lead to an expansion of polyglutamine tract in the resulting mutated
      HTT protein, which is toxic, is the causative factor of HD. Although the
      molecular basis of HD is known, there is no known cure for this disease other
      than symptomatic relief treatment approaches. The toxicity of mutHTT appears to
      be more detrimental to striatal medium spiny neurons, which degenerate in this
      disease. Therapeutic strategies addressing a reduction in the mutHTT content at
      the transcriptional level using zinc finger proteins and at the translational
      level with RNA interference and antisense oligonucleotides or promoting the
      proteosomal degradation of mutHTT are being studied extensively in preclinical
      models and also to a limited extent in clinical trials. The post-translational
      modification of mutHTT is another possibility that is currently being
      investigated for drug development. In addition to the pharmacological approaches,
      several lines of evidence suggested the potential therapeutic use of stem cell
      therapy, in particular using the patient-derived induced pluripotent stem cells,
      to replace the lost striatal neurons. The multi-pronged clinical investigations
      currently underway may identify therapies and potentially improve the quality of
      life for the HD patients in future.

PMID- 27698681
TI  - Pain control by melatonin: Physiological and pharmacological effects.
AB  - Pain and anxiety are the most common neurological responses to many harmful or
      noxious stimuli and their management clinically is often challenging. Many of the
      frequently used morphine-based drugs, non-steroid anti-inflammatory drugs and
      acetaminophen, while efficient for treating pain, lead to patients suffering from
      several unwanted side effects. Melatonin, produced from the pineal body is a
      hormone of darkness, is involved in the control of circadian rhythms, and exerts
      a number of pharmacological effects. Melatonin mediates its actions through
      MT1/MT2 melatonin receptors on the cell membrane and also through RZR/ROR nuclear
      orphan receptors. Chronic pain syndromes are often associated with the
      desynchronization of circadian and biological rhythms, which also cause
      disturbances in the sleep-wake cycle. Melatonin-mediated analgesic effects seem
      to involve beta-endorphins, GABA receptor, opioid receptors and the nitric oxide
      arginine pathway. The effectiveness of melatonin as an analgesic and anxiolytic
      agent has been demonstrated in various animal models of pain and this led to the
      use of melatonin clinically in different pathological conditions and also in
      patients undergoing surgery. Melatonin was found to be effective in many of these
      cases as an anxiolytic and analgesic agent, indicating its clinical application.

PMID- 27698680
TI  - Status epilepticus: Using antioxidant agents as alternative therapies.
AB  - The epileptic state, or status epilepticus (SE), is the most serious situation
      manifested by individuals with epilepsy, and SE events can lead to neuronal
      damage. An understanding of the molecular, biochemical and physiopathological
      mechanisms involved in this type of neurological disease will enable the
      identification of specific central targets, through which novel agents may act
      and be useful as SE therapies. Currently, studies have focused on the association
      between oxidative stress and SE, the most severe epileptic condition. A number of
      these studies have suggested the use of antioxidant compounds as alternative
      therapies or adjuvant treatments for the epileptic state.

PMID- 27698682
TI  - Microwaves and Alzheimer's disease.
AB  - Alzheimer's diseases (AD) is the most common type of dementia and a
      neurodegenerative disease that occurs when the nerve cells in the brain die. The
      cause and treatment of AD remain unknown. However, AD is a disease that affects
      the brain, an organ that controls behavior. Accordingly, anything that can
      interact with the brain may affect this organ positively or negatively, thereby
      protecting or encouraging AD. In this regard, modern life encompasses microwaves
      for all issues including industrial, communications, medical and domestic
      tenders, and among all applications, the cell phone wave, which directly exposes
      the brain, continues to be the most used. Evidence suggests that microwaves may
      produce various biological effects on the central nervous system (CNS) and many
      arguments relay the possibility that microwaves may be involved in the
      pathophysiology of CNS disease, including AD. By contrast, previous studies have
      reported some beneficial cognitive effects and that microwaves may protect
      against cognitive impairment in AD. However, although many of the beneficial
      effects of microwaves are derived from animal models, but can easily be
      extrapolated to humans, whether microwaves cause AD is an important issue that is
      to be addressed in the current review.

PMID- 27698684
TI  - Molecular examination of bone marrow stromal cells and chondroitinase ABC
      assisted acellular nerve allograft for peripheral nerve regeneration.
AB  - The present study aimed to evaluate the molecular mechanisms underlying
      combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase
      ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the
      sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors
      and Wistar rats (n=48) were randomly divided into the following groups: Group I,
      Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM
      only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC
      group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC
      treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve
      growth factor, brain-derived neurotrophic factor and vascular endothelial growth
      factor in the regenerated tissues were detected by reverse transcription
      quantitative polymerase chain reaction and immunohistochemistry. Axonal
      regeneration, motor neuron protection and functional recovery were examined by
      immunohistochemistry, horseradish peroxidase retrograde neural tracing and
      electrophysiological and tibialis anterior muscle recovery analyses. It was
      observed that combination therapy enhances the growth response of the donor nerve
      locally as well as distally, at the level of the spinal cord motoneuron and the
      target muscle organ. This phenomenon is likely due to the propagation of
      retrograde and anterograde transport of growth signals sourced from the graft
      site. Collectively, growth improvement on the donor nerve, target muscle and
      motoneuron ultimately contribute to efficacious axonal regeneration and
      functional recovery. Thorough investigation of molecular peripheral nerve injury
      combinatorial strategies are required for the optimization of efficacious therapy
      and full functional recovery following ANA.

PMID- 27698683
TI  - DNA methylation in spermatogenesis and male infertility.
AB  - Infertility is a significant problem for human reproduction, with males and
      females equally affected. However, the molecular mechanisms underlying male
      infertility remain unclear. Spermatogenesis is a highly complex process involving
      mitotic cell division, meiosis cell division and spermiogenesis; during this
      period, unique and extensive chromatin and epigenetic modifications occur to
      bring about specific epigenetic profiles in spermatozoa. It has recently been
      suggested that the dysregulation of epigenetic modifications, in particular the
      methylation of sperm genomic DNA, may serve an important role in the development
      of numerous diseases. The present study is a comprehensive review on the topic of
      male infertility, aiming to elucidate the association between sperm genomic DNA
      methylation and poor semen quality in male infertility. In addition, the current
      status of the genetic and epigenetic determinants of spermatogenesis in humans is
      discussed.

PMID- 27698685
TI  - Targeting CRMP-4 by lentivirus-mediated RNA interference inhibits SW480 cell
      proliferation and colorectal cancer growth.
AB  - The aim of the present study was to investigate the expression level of collapsin
      response mediator protein 4 (CRMP-4) in human colorectal cancer (CRC) tissue and
      to evauluate its impact on SW480 cell proliferation, in addition to tumor growth
      in a mouse xenograft model. Clinical CRC tissue samples were collected to detect
      the CRMP-4 protein expression levels using western blot and immunohistochemistry
      analyses. A specific small interfering RNA sequence targeting the CRMP-4 gene
      (DPYSL3) was constructed and transfected into an SW480 cell line using a
      lentivirus vector to obtain a stable cell line with low expression of CRMP-4. The
      effectiveness of the interference was evaluated using western blot and reverse
      transcription-quantitative polymerase chain reaction, and the cell proliferation
      was determined using MTT and BrdU colorimetric methods. Tumor growth was assessed
      by subcutaneously inoculating the constructed cells into BALB/c nude mice. The
      protein expression levels of CRMP-4 were markedly increased in colon tumor tissue
      of the human samples. The proliferation of SW480 cells and the tumor growth rate
      in nude mice of the si-CPMR-4 group were evidently depressed compared with the si
      scramble group. Thus, the present results suggest that CRMP-4 may be involved in
      the pathogenesis of CRC.

PMID- 27698686
TI  - Osthole decreases renal ischemia-reperfusion injury by suppressing JAK2/STAT3
      signaling activation.
AB  - Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury.
      The pathogenetic mechanisms underlying renal I/R injury involve inflammation,
      oxidative stress and apoptosis. Osthole is a coumarin derivative that exhibits
      potential anti-inflammatory activity. The aim of the present study was to
      investigate the effect of osthole in renal I/R injury and its underlying
      mechanism. Renal I/R injury was induced by clamping the left renal artery for 45
      min followed by 24 h reperfusion with the contralateral nephrectomy. A total of
      70 rats were randomly assigned to seven groups (n=10 per group): Sham; IRI; and
      osthole (0, 5, 10, 20 and 40 mg/kg) groups. Rats were administered
      intraperitoneally with osthole 45 min prior to renal ischemia. Serum and renal
      tissue were harvested 24 h after reperfusion. Renal function and histological
      changes were assessed. In addition, the mRNA and protein expression of tumor
      necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and interleukin-6 (IL-6)
      in renal tissue and serum were evaluated using quantitative polymerase chain
      reaction and ELISA assays, respectively. The protein expression levels of p65, p
      p65, janus kinase 2 (JAK2), p-JAK2, signal transducer and activator of
      transcription 3 (STAT3) and p-STAT3 were measured using western blot analysis.
      The results indicate that osthole pretreatment was able to significantly
      attenuate the renal dysfunction in a dose-dependent manner, histological changes
      and the expression of TNF-alpha, IL-8, IL-6, p-JAK2, p-STAT3 and p-p65 induced by
      renal I/R injury. However, neither osthole or I/R injury affected the expression
      p65, JAK2 and STAT3. Osthole pretreatment is able to reduce renal I/R injury by
      abrogating inflammation and the mechanism is partially involved in suppressing
      JAK2/STAT3 activation. Thus, osthole may be a novel practical strategy for the
      mitigation of renal I/R injury.

PMID- 27698687
TI  - Guided bone regeneration with local zoledronic acid and titanium barrier: An
      experimental study.
AB  - The aim of this study was to evaluate the effects on new bone formation of
      autogenous blood alone or in combination with zoledronic acid (ZA), a beta
      tricalcium phosphate (beta-TCP) graft or ZA plus a beta-TCP graft placed under
      titanium barriers. For this purpose, eight adult male New Zealand white rabbits
      were used in the study, each with four titanium barriers fixed around four sets
      of nine holes drilled in the calvarial bones. The study included four groups,
      each containing 2 rabbits. In the autogenous blood (AB group), only autogeneous
      blood was placed under the titanium barriers. The three experimental groups were
      the AB+ZA group, with autogenous blood plus ZA, the AB+beta-TCP group, with
      autogeneous blood plus a beta-TCP graft, and the AB+beta-TCP+ZA group, with
      autogeneous blood plus a beta-TCP graft and ZA mixture under the titanium
      barriers. The animals were sacrificed after 3 months. The amounts of new bone
      formation identified histomorphometrically were found to be higher after 3 months
      than at the time of surgery in all groups. The differences between the groups
      were examined with histomorphometric analysis, and statistically significant
      differences were identified at the end of the 3 months. The bone formation rate
      in the AB+beta-TCP+ZA group was determined to be significantly higher than that
      in the other groups (P<0.05). In the AB+ZA and AB+beta-TCP groups, the bone
      formation rate was determined to be significantly higher than that in the AB
      group (P<0.05). No statistically significant difference in bone formation rate
      was observed between the AB+beta-TCP and AB+ZA groups. Local ZA used with
      autogeneous blood and/or graft material appears to be a more effective method
      than the use of autogeneous blood or graft alone in bone augmentation executed
      with a titanium barrier.

PMID- 27698688
TI  - Specific clinical manifestations of Nocardia: A case report and literature
      review.
AB  - Nocardiosis is a rare bacterial infection of either the lungs (pulmonary) or body
      (systemic) that usually affects immunocompromised individuals. It is caused by
      Gram-positive, aerobic actinomycetes of the Nocardia genus. Multiple high-density
      sheet shadows in both lungs along with nodules or cavities are the most common
      presentations of nocardiosis, whereas a large pulmonary mass is considered to be
      rare. However, there is no specificity in the clinical manifestation of the
      disease. Therefore, isolation and identification of Nocardia strains is the only
      reliable diagnostic method. The present study describes the cases of two male
      patients of Asian descent with nocardiosis. Chest computed tomography scans
      showed a suspected tumor mass in both patients. Microscopic analysis and
      culturing of tissue samples obtained using a bronchoscope detected the presence
      of Nocardia wallacei. Neither patient showed signs of immunosuppression. The
      present study aimed to improve the understanding of lung nocardiosis and
      demonstrated that pulmonary nocardiosis should be suspected in the case of non
      immunocompromised patients with a large mass in the lung. Furthermore, a review
      of the literature on infection with Nocardia was conducted.

PMID- 27698689
TI  - Achievement of a target dose of bisoprolol may not be a preferred option for
      attenuating pressure overload-induced cardiac hypertrophy and fibrosis.
AB  - Bisoprolol is a drug that acts via the mechanism of specifically and selectively
      inhibiting the beta1-adrenoreceptor in cardiac myocytes, and provides a pure
      reduction of heart rate without changing other cardiac parameters. It has long
      been clinically used to treat cerebrovascular and cardiovascular illnesses.
      However, there is little information available on whether the role of bisoprolol
      in the attenuation of ventricular remodeling is dependent upon the achievement of
      a target dose, and whether it must be used as a preferred option. The aim of the
      present study was to clarify the underlying benefits of bisoprolol in the
      attenuation of pressure overload-induced cardiac hypertrophy and fibrosis at
      different doses. C57BL/6J male mice, aged 6-8 weeks, were treated with saline or
      one of three different doses of bisoprolol (Biso: 2.5, 5 or 10 mg/kg/day) for 8
      weeks from day 1 after aortic banding (AB). A number of mice underwent sham
      surgery and were treated with saline or bisoprolol. The mice were randomly
      assigned into the sham (n=24) and AB (n=62) groups. The results revealed that
      bisoprolol had a protective role against the cardiac hypertrophy, fibrosis and
      dysfunction caused by AB. This was determined on the basis of heart/body and
      lung/body weight ratios and heart weight/tibia length ratios, as well as
      echocardiographic and hemodynamic parameters, histological analysis, and the gene
      expression levels of hypertrophic and fibrotic markers. The present study
      revealed that administration of bisoprolol for a long time period may enhance its
      role in the prevention of cardiac hypertrophy and fibrosis induced by AB, whereas
      no statistically significant difference was observed between the middle- and high
      doses. These observations indicated that the function of bisoprolol in protecting
      against cardiac hypertrophy, fibrosis and dysfunction is time-dependent.
      Furthermore, it is proposed that a middle dose of bisoprolol may be a better
      option for patients with cardiovascular illnesses, particularly those undertaking
      coronary artery bypass graft and cardiac pacemaker surgeries. These promising
      results require further clinical investigation.

PMID- 27698690
TI  - Effect of glycerol on sustained insulin release from PVA hydrogels and its
      application in diabetes therapy.
AB  - The present study aimed to investigate the effects of glycerol on the physical
      properties and release of an insulin-loaded polyvinyl alcohol (PVA) hydrogel
      film. The insulin-loaded hydrogel composite film was produced using the freeze
      thawing method, after which the in vitro swelling ratio, transmittance and
      insulin release, and the in vivo pharmacodynamics, of hydrogels containing
      various volumes of glycerol were investigated. The results demonstrated that the
      addition of glycerol reduced the swelling ratio and increased the softness of the
      PVA hydrogel film. An analysis of insulin release in vitro and of the
      hypoglycemic effects in rats demonstrated that the PVA hydrogel film had a
      sustained release of insulin and long-acting effect over 10 days. The results of
      the present study suggested that, as a hydrophilic plasticizer, glycerol was able
      to enhance the release of insulin in the early stage of release profile by
      enhancing the formation of water channels, although the total swelling ratio was
      decreased. Therefore, the insulin-loaded glycerol/PVA hydrogel film may be a
      promising sustained-release preparation for the treatment of diabetes.

PMID- 27698691
TI  - Overexpression of LRIG1 regulates PTEN via MAPK/MEK signaling pathway in
      esophageal squamous cell carcinoma.
AB  - The present study aimed to evaluate the role of leucine-rich repeats and
      immunoglobulin-like domain protein 1 (LRIG1) in the regulation of phosphatase and
      tensin homolog (PTEN) expression in esophageal carcinogenesis. LRIG1 was
      overexpressed in esophageal squamous cell carcinoma (ESCC) cell lines, and the
      effect of LRIG1 overexpression on the mRNA and protein expression levels of PTEN
      was evaluated by reverse transcription-quantitative polymerase chain reaction and
      western blotting. Furthermore, the effects of LRIG1 overexpression on the cell
      cycle distribution and apoptosis of ESCC cells were examined by flow cytometry.
      Various cell signaling pathway inhibitors were used to assess the effects of
      LRIG1 on downstream signaling in ESCC cell lines. In addition, the association
      between LRIG1 and PTEN expression was examined in 48 samples from patients with
      ESCC. LRIG1 overexpression was demonstrated to downregulate PTEN expression in
      ESCC cell lines, and promote their proliferation and inhibit apoptosis. In
      addition, LRIG1-mediated suppression of PTEN expression was inhibited by the
      U0126 inhibitor, which suggests that LRIG1 may inhibit the activation of PTEN
      signaling molecules by triggering the mitogen-activated protein kinase
      (MAPK)/MAPK kinase 1 (MEK) signaling pathway. In conclusion, the present study
      demonstrated that overexpression of LRIG1 significantly and adversely affected
      the survival of ESCC cells, and that the MAPK/MEK signaling pathway may be
      responsible for the repression of PTEN expression and function.

PMID- 27698692
TI  - Reversal effect and mechanism of Ginkgo biloba exocarp extracts in multidrug
      resistance of mice S180 tumor cells.
AB  - The aim of the present study was to investigate the reversal effect and its
      related mechanism of Ginkgo biloba exocarp extracts (GBEEs) in obtained multidrug
      resistance (MDR) of mice S180 tumor cells in vitro and in vivo. In order to
      simulate the clinical PFC [cis-dichlorodiamineplatinum, cisplatin (DDP) +
      fluorouracil (FU), FU+cyclophosphamide and cyclophosphamide] scheme, a gradually
      increasing dose was administered in a phased induction in order to induce S180
      cells in vivo and to make them obtain multidrug resistance. The results in vitro
      demonstrated that GBEE could significantly increase the IC50 of DDP on S180 MDR
      cells, increase the accumulation of Adriamycin (ADR) and rhodamine 123 (Rho 123),
      and reduce the efflux of Rho 123 of S180 MDR cells. The results from the in vivo
      treatment with a combination of GBEE and DDP to S180 MDR ascites tumor in mice
      demonstrated that each dose of GBEE could effectively reverse the drug-resistance
      of S180 MDR cells to DDP in order to extend the survival time of mice with ascite
      tumors and inhibit tumor growth in solid tumor mice. In addition, GBEE
      effectively inhibited the expression of MDR-1 mRNA and multidrug resistance
      associated protein-1 mRNA in S180 MDR cells of ascites tumor in mice and improved
      the expression levels of cytokines, including interleukin (IL)-3, IL-18 and
      interferon-gamma in the blood serum of S180 MDR tumor-bearing mice. The present
      study showed that the mechanism of GBEE reversal of MDR may be associated with
      the inhibition of the functional activity of P-glycoprotein, the downregulation
      of drug resistance related gene expression of S180 MDR cells and the improvement
      of the production of related serum cytokines of S180 MDR tumor mice.

PMID- 27698693
TI  - ATP-induced cardioprotection against myocardial ischemia/reperfusion injury is
      mediated through the RISK pathway.
AB  - The aim of the present study was to examine the post-infarct acute effect of
      adenosine-5'-triphosphate (ATP) on myocardial infarction (MI) size as well as its
      precise molecular mechanism. Sixty New Zealand white male rabbits were exposed to
      40 min of ischemia followed by 180 min of reperfusion. The rabbits were
      intravenously administered 3 mg/kg of ATP (ATP group) or saline (control group)
      immediately after reperfusion and maintained throughout the first 30 min. The
      wortmannin+ATP, PD-98059+ATP, and 5-hydroxydecanoic acid (5-HD) sodium salt+ATP
      groups were separately injected with wortmannin (0.6 mg/kg), PD-98059 (0.3
      mg/kg), and 5-HD (5 mg/kg) 5 min prior to ATP administration. MI size was
      calculated as the percentage of the risk area in the left ventricle. Myocardial
      apoptosis was determined using a TUNEL assay. Western blot analysis was performed
      to examine the levels of protein kinase B (Akt)/p-Akt and extracellular signal
      regulated kinase (ERK)/p-ERK in the ischemic myocardium, 180 min after
      reperfusion. The infarct size was significantly smaller in the ATP group than in
      the control group (p<0.05). The infarct size-reducing effect of ATP was
      completely blocked by wortmannin, PD-98059 and 5-HD. Compared with the control
      group, cardiomyocyte apoptosis was significantly reduced in the ATP group, while
      this did not occur in the wortmannin+ATP, PD-98059+ATP and 5-HD+ATP groups.
      Western blot analysis revealed a higher myocardial expression of p-Akt and p-ERK
      180 min following reperfusion in the ATP versus the control group. In conclusion,
      cardioprotection by postischemic ATP administration is mediated through
      activation of the reperfusion injury salvage kinase (RISK) pathway and opening of
      the mitochondrial ATP-dependent potassium channels.

PMID- 27698694
TI  - Diagnosing pyogenic, brucella and tuberculous spondylitis using histopathology
      and MRI: A retrospective study.
AB  - The present study examined the histopathological and magnetic resonance imaging
      (MRI) features of pyogenic, brucella and tuberculous spondylitis (PS, BS and TS,
      respectively). A total of 22 PS, 20 BS and 20 TS patients were included in the
      study. Histopathological examination was used to assess the lesion structure and
      composition, and the MRI observation identified the lesion location and signal
      features. The following histopathological and MRI features were identified
      significantly more in patients with PS than in patients with BS and TS:
      Predominant neutrophil infiltration, abnormal intervertebral disk signal, lesions
      on the ventral and lateral sides of the vertebral bodies, and thick and irregular
      abscess walls. The following histopathological and MRI features were identified
      significantly more in patients with BS than in patients with PS and TS:
      Predominant lymphocyte infiltration, new bone formation, epithelioid granuloma,
      lesions on the ventral sides of the vertebral bodies, no, or very mild, vertebral
      body deformation, no abnormal paraspinal soft tissue signal, no intraosseous or
      paraspinal abscesses, and thin and irregular abscess walls. The following
      histopathological and MRI features were identified significantly more in patients
      with TS than in patients with BS and PS: Sequestrum, Langerhans giant cells,
      caseous necrosis, lesions primarily in the thoracic region and on the lateral
      sides of the vertebral bodies, no obvious intervertebral disk damage, obvious
      vertebral body deformation, abnormal paraspinal soft tissue signal, intraosseous
      or paraspinal abscesses, and thin and smooth abscess walls. In conclusion, it can
      be suggested that these significant differences in histopathological and MRI
      features between the three different types of spondylitis may contribute towards
      the differential diagnosis of the diseases.

PMID- 27698695
TI  - Rare case of disseminated fusariosis in a young patient with graft vs. host
      disease following an allogeneic transplant.
AB  - Fusarium infection is a severe fungal infection caused by fungi of the genus
      Fusarium. It most commonly occurs in immunocompromised patients with malignant
      hematological comorbidities or secondary to hematopoietic stem cell transplant.
      The classical route of contamination is through inhalation but infection may also
      occur through contiguity with a skin lesion. This report describes the case of a
      24-year-old woman who developed graft-vs.-host disease (GVHD) at 220 days after
      receiving an allogeneic stem cell transplant from a sibling donor for Hodgkin
      disease. On day 330 after transplant the patient presented with fever and several
      painful subcutaneous, tender, red nodules with ulcerative and necrotic features
      on the pelvic region and right leg, extensive glass infiltrative lesions in the
      lungs and pansinusitis; however, the patient did not have onychomycosis.
      Following skin biopsy, culture of cutaneous lesions, computed tomography (CT)
      scanning of the lungs and CT scanning and magnetic resonance imaging of facial
      sinuses the patient was diagnosed with disseminated Fusarium species infection.
      Despite intensive treatment with voriconazole, the patient succumbed with
      respiratory insufficiency on day 400 after transplant. This case is noteworthy
      because the patient did not have any additional risk associated with the
      allogeneic transplant; there was no transplant mismatch, no severe neutropenia
      and no prior clinical signs of onychomycosis. The association of skin lesions
      with GVHD lesions increased the initial immunosuppression and delayed diagnosis.

PMID- 27698696
TI  - Rhodiola rosea, folic acid, zinc and biotin (EndEP(r)) is able to improve
      ejaculatory control in patients affected by lifelong premature ejaculation:
      Results from a phase I-II study.
AB  - The therapeutic armamentarium currently available for the treatment of premature
      ejaculation (PE) is not highly satisfactory. However, phytotherapeutics appear to
      be an interesting option for PE management. The present study aimed to evaluate
      the tolerability and efficacy of a phytotherapeutic combination of Rhodiola
      rosea, folic acid, biotin and zinc (EndEP(r)) in the treatment of patients
      affected by lifelong PE. All patients affected by lifelong PE who were attending
      three Urological Institutions from July to December 2014 were enrolled in this
      prospective, multicentre, phase I-II study. All patients were assigned to receive
      oral tablets of EndEP(r) (one tablet per day) for 90 days. Clinical and
      instrumental analyses were carried out at enrolment and at the end of the study.
      International Prostatic Symptom Score (IPSS), International Index of Erectile
      Function (IIEF)-15, Premature Ejaculation Diagnostic Tool (PEDT) and Short Form
      (SF)-36 questionnaires were used. The intravaginal ejaculation latency time
      (IELT) for each event was also evaluated using the stop-watch technique. The main
      outcome measure was the difference from baseline in PEDT questionnaire and mean
      IELT at the end of the follow-up period. In total, 91 patients (mean age, 32.3+/
      5.6 years) were analysed. The baseline questionnaires mean scores were 1.1+/-1.6,
      26.1+/-2.9, 15.3+/-3.4 and 98.2+/-0.5, for IPSS, IIEF-15, PEDT and SF-36,
      respectively. The mean IELT at baseline was 73.6+/-46.9s. At the follow-up
      examination (90 days after the start of treatment), no statistically significant
      differences were identified in terms of IPSS (1.4+/-1.5) or IIEF-15 (26.3+/-3.1)
      compared with the pre-treatment values (P=0.19 and P=0.64, respectively). A
      statistically significant difference was detected between the mean IELT at
      enrolment and after treatment (73.6+/-46.9 vs. 102.3+/-60.0; P<0.001) and SF-36
      questionnaire (98.2+/-0.5 vs. 99.4+/-0.1; P<0.001). Fifty-five patients reported
      improvement in the control of ejaculation (60.4%). Very few adverse events were
      reported (4.4%). In conclusion, it was found that EndEP(r) significantly improved
      ejaculatory control and the quality of sexual life in patients affected by
      lifelong PE, with a very low rate of adverse events.

PMID- 27698697
TI  - Oncogenic role of epithelial cell transforming sequence 2 in lung adenocarcinoma
      cells.
AB  - Lung adenocarcinoma, which is the most common non-small cell lung cancer, is the
      leading cause of death from cancer worldwide. Epithelial cell transforming
      sequence 2 (ECT2) is frequently upregulated and acts as an oncogene in various
      human cancers. In addition, ECT2 was reported to be upregulated in early stage
      lung adenocarcinoma. However, the detailed role of ECT2 in mediating the
      malignant phenotypes of lung adenocarcinoma cells has not previously been
      elucidated. Reverse transcription-quantitative polymerase chain reaction and
      western blot analysis were used to examine ECT2 mRNA and protein expression
      levels, respectively. MTT, wound healing and Transwell assays were conducted to
      determine cell proliferation, migration and invasion abilities, respectively. In
      the present study, ECT2 was significantly upregulated in lung adenocarcinoma cell
      lines (H650, EKVX, HCC4006, HCC827, HCC2935, Hop62 and A549), as compared with a
      normal lung epithelial cell line (BEAS-2B). Moreover, knockdown of ECT2, induced
      by transfection with ECT2 siRNA, significantly inhibited the proliferation of
      lung adenocarcinoma A549 cells, whereas overexpression of ECT2 enhanced A549 cell
      proliferation. Furthermore, knockdown of ECT2 expression suppressed the migration
      and invasion of A549 cells, whereas overexpression of ECT2 enhanced the migration
      and invasion abilities of A549 cells. Notably, inhibition of ECT2 also suppressed
      the expression levels of N-cadherin and vimentin, whereas it enhanced the
      expression level of E-cadherin, indicating that ECT2 is associated with the
      epithelial-mesenchymal transition in A549 cells. On the contrary, overexpression
      of ECT2 enhanced the expression levels of N-cadherin and vimentin, whereas it
      reduced the expression level of E-cadherin in A549 cells. In conclusion, the
      results of the present study suggest that ECT2 has an oncogenic role in lung
      adenocarcinoma cells. Therefore, ECT2 may be a potential novel target for the
      treatment of lung adenocarcinoma.

PMID- 27698698
TI  - Downregulation of microRNA-132 indicates progression in hepatocellular carcinoma.
AB  - Although miR-132 has been studied in various human tumors, few studies have
      investigated the role of miR-132 in hepatocellular carcinoma (HCC). The present
      study aimed to evaluate the associations between miR-132 and clinicopathological
      parameters, including recurrence, in patients with HCC. Reverse transcription
      quantitative polymerase chain reaction analysis was used to detect the expression
      levels of miR-132 in 95 cases of HCC and their corresponding non-cancerous liver
      tissues. Th e associations between miR-132 expression levels and
      clinicopathological characteristics, including recurrence, were investigated in
      patients with HCC. miR-132 expression levels were significantly reduced in HCC
      tissues, as compared with adjacent non-cancerous tissues (1.9245+/-0.7564 vs.
      2.7326+/-1.1475; P<0.001). The area under curve (AUC) of receiver operating
      characteristic (ROC) used to distinguish cancerous and non-cancerous tissues was
      0.711 for miR-132 expression (95% confidence interval, 0.637-0.785; P<0.001) and
      the optimal cut-off value was 2.25. Expression levels of miR-132 were
      significantly reduced in the distant metastasis (P=0.031), advanced clinical TNM
      stage (P=0.022), hepatitis B virus-positive (P<0.001), NM23-expressed (P=0.034),
      high Ki-67 labeling index (LI; P=0.005) and tumor infiltration or no capsule
      groups (P=0.026). Spearman correlation analysis demonstrated that miR-132 was
      significantly correlated with hepatitis B virus infection (r=-0.351; P<0.001),
      NM23 (r=-0.220; P=0.032), Ki-67 LI (r=-0.264; P=0.010) and tumor capsule (r=
      0.207; P=0.044). Kaplan-Meier analysis with the log-rank test indicated an
      approximate difference of 8 months, although miR-132 may exhibit inferior values
      for the prediction of recurrence in HCC patients (50.95 vs. 58.68 months;
      P=0.512). Therefore, the findings of the present study indicated that miR-132 is
      downregulated in HCC and may serve as a tumor suppressor in its progression.

PMID- 27698699
TI  - Decorin reduces hypertrophic scarring through inhibition of the TGF-beta1/Smad
      signaling pathway in a rat osteomyelitis model.
AB  - Chronic osteomyelitis is a bone infection that results in hypertrophic scarring
      of the soft tissue surrounding the infected bone. This scarring can create
      functional problems and its treatment is challenging. The aim of the present
      study was to evaluate the efficacy of decorin in treating scar formation in
      osteomyelitis and the underlying mechanism of its action. A rat osteomyelitis
      model was used, and animals were divided into three groups, as follows: Group A
      (control), group B (osteomyelitis model) and group C (decorin-treated). X-ray
      scans, hematoxylin and eosin (H&E) staining and Masson's trichrome staining were
      performed to observe changes in femur and muscle tissue. In order to assess the
      role of the transforming growth factor beta1 (TGF-beta1)/Smad signaling pathway
      in scar formation in osteomyelitis, alterations in muscle tissue morphology and
      in the activation of key members of the TGF-beta1/Smad signaling pathway were
      investigated in groups A and B. According to the results of H&E staining, evident
      fibrosis in muscle tissue were observed at days 14 and 28 in group B.
      Simultaneously, the expression levels of key members of the TGF-beta1/Smad
      signaling pathway were increased. Subsequent to treatment with decorin in group
      C, scarring was reduced, and significant downregulation of collagen I, TGF-beta1,
      phosphorylated (p)Smad2 and pSmad3 protein expression levels was observed at days
      14 and 28 compared with the osteomyelitis group. In conclusion, these results
      suggest that activation of TGF-beta1 may serve an important role in the formation
      of scars in osteomyelitis and that decorin can reduce scar formation in an
      osteomyelitis rat model through inhibition of the TGF-beta1/Smad signaling
      pathway.

PMID- 27698700
TI  - Matrix metalloproteinase 14 participates in corneal lymphangiogenesis through the
      VEGF-C/VEGFR-3 signaling pathway.
AB  - The aim of the present study was to investigate the roles of matrix
      metalloproteinase 14 (MMP-14) in corneal inflammatory lymphangiogenesis. The
      expression of MMP-14 in vivo was detected by immunohistochemistry, reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot
      assays, under various corneal conditions. pCMV-MMP-14 or empty pCMV vectors were
      injected into mouse corneal stroma, 3 days after suture placement in a standard
      suture-induced inflammatory corneal neovascularization assay. The outgrowth of
      blood and lymphatic vessels and macrophage recruitment were analyzed using
      immunofluorescence. The expression levels of vascular endothelial growth factor
      (VEGF) subtypes were tested by RT-qPCR. MMP-14 expression was upregulated
      significantly following various corneal injuries. The results demonstrated, for
      the first time, that MMP-14 strongly promotes corneal lymphangiogenesis and
      macrophage infiltration during inflammation. Furthermore, expression levels of
      VEGF-C and VEGF receptor-3, but not other VEGF components, were significantly
      upregulated by the intrastromal delivery of MMP-14 during corneal
      lymphangiogenesis. In conclusion, this study indicates that MMP-14 is critically
      involved in the processes of lymphangiogenesis. Inhibition of MMP-14 may provide
      a viable treatment for transplant rejection and other lymphatic disorders.

PMID- 27698701
TI  - Alien hand syndrome following corpus callosum infarction: A case report and
      review of the literature.
AB  - Alien hand syndrome (AHS) is characterized by involuntary and autonomous activity
      of the affected limbs, and consists of the frontal, callosal and posterior AHS
      variants. The callosal subtype, resulting from damage to the corpus callosum,
      frequently features intermanual conflict. However, infarction of the corpus
      callosum is rare due to abundant blood supply. The present study reported a case
      of AHS (callosal subtype, in the right hand) caused by callosal infarction.
      Infarction of the left corpus callosum was confirmed with magnetic resonance
      imaging. In addition, magnetic resonance angiography and digital subtraction
      angiography examinations revealed multiple lesions in the feeding arteries.
      Subsequent to antiplatelet therapy for 2 weeks following admission, the patient
      gradually recovered. Furthermore, the current study reviewed 31 previously
      reported cases of AHS following callosal infarction in the literature.

PMID- 27698702
TI  - Effect of early enteral nutrition on patients with digestive tract surgery: A
      meta-analysis of randomized controlled trials.
AB  - Postoperative early enteral nutrition (EEN) is useful for the effective recovery
      of patients that have undergone surgery. However, the feasibility and efficacy of
      EEN in patients with digestive tract surgery remain inconclusive. In the present
      meta-analysis, the PubMed, EMBASE, Web of Science, The Cochrane Library, China
      National Knowledge Infrastructure and VIP databases were searched to identify
      controlled trials of patients with and without EEN following digestive tract
      surgery between October, 1966 and December, 2014. Methodological quality
      assessment was carried out for each of the included studies. For estimation of
      the analysis indexes, relative risk (RR) was used as the effect size of the the
      categorical variable, while the weighted mean difference (MD) was used as the
      effect size of the continuous variable. The meta-analysis was conducted using
      RevMan 5.2 software. Eleven randomized controlled trials involving 1,095 patients
      were included in the meta-analysis. The results revealed that, EEN in patients
      with digestive tract surgery was more effective in decreasing the incidence of
      infectious [RR=0.50, 95% confidence interval (CI): 0.38, 0.67; P<0.01] and non
      infectious complications (RR=0.72, 95% CI: 0.43, 1.22; P<0.05) and shortening the
      length of first bowel action (MD=-4.10, 95% CI: -5.38, -2.82; P<0.05). It also
      had a significant influence on increasing the serum albumin (MD=2.87, 95% CI:
      1.03, 4.71; P<0.05) and serum prealbumin (MD=0.04, 95% CI: 0.02, 0.05; P<0.05)
      levels. In conclusion, the results of the study have shown that EEN in patients
      with digestive tract surgery improved the nutritional status, reduced the risk of
      postoperative complications, shortened the length of hospital stay and promoted
      the functional recovery of the digestive system.

PMID- 27698703
TI  - Emergency treatment and nursing of children with severe pneumonia complicated by
      heart failure and respiratory failure: 10 case reports.
AB  - Pneumonia refers to lung inflammation caused by different pathogens or other
      factors, and is a common pediatric disease occurring in infants and young
      children. It is closely related to the anatomical and physiological
      characteristics of infants and young children and is more frequent during winter
      and spring, or sudden changes in temperature. Pneumonia is a serious disease that
      poses a threat to children's health and its morbidity and mortality rank first,
      accounting for 24.5-65.2% of pediatric inpatients. Due to juvenile age, severe
      illness and rapid changes, children often suffer acute heart failure, respiratory
      failure and even toxic encephalopathy at the same time. The concurrence in
      different stages of the process of emergency treatment tends to relapse, which
      directly places the lives of these children at risk. Severe pneumonia constitutes
      one of the main causes of infant mortality. In the process of nursing children
      with severe pneumonia, intensive care was provided, including condition
      assessment and diagnosis, close observation of disease, keeping the airway
      unblocked, rational oxygen therapy, prevention and treatment of respiratory and
      circulatory failure, support of vital organs, complications, and health
      education. The inflammatory response was proactively controlled, to prevent
      suffocation and reduce mortality. In summary, positive and effective nursing can
      promote the rehabilitation of children patients, which can be reinforced with
      adequate communication with the parents and/or caretakers.

PMID- 27698704
TI  - Anti-angiogenic effect of total saponins of Rhizoma Dioscorea nipponica on
      collagen induced-arthritis in rats.
AB  - Rheumatoid arthritis (RA) is a common chronic autoimmune and incurable disease.
      The aim of the present study was to investigate the therapeutic effect and
      mechanism of the total saponins of Rhizoma Dioscorea nipponica (TSRDN) in RA. A
      collagen induced-arthritis (CIA) rat model was established. CIA rats were
      randomly divided into three groups and lavaged with an equal volume of solvent
      (CIA group), TSRDN (25 mg/kg/day, RDN group) and tripterygium (TP; 12 mg/kg/day,
      TP group) for 21 days, respectively. Normal rats served as a control group.
      Hematoxylin-eosin (HE) staining was used to observe the histopathological injury
      of synovial tissues. The level of CD31, which used for marking and counting,
      micro vessel density (MVD) and the expression levels of vascular endothelial
      growth factor (VEGF) and signal transducer and activator of transcription 3
      (STAT3) were detected by immunohistochemical analysis. Additionally, the DNA
      binding activity of nuclear factor-kappaB (NF-kappaB) was determined using an
      ELISA kit. HE staining showed obvious synovial hyperplasia, inflammatory cell
      infiltration, pannus formation, cartilage and bone erosion in the CIA group rats.
      In addition, compared with control group, the level of MVD, the expression of
      VEGF and STAT3, and the DNA-binding activity of NF-kappaB were all increased in
      CIA group rat synovial tissue (all P<0.01); however, TSRDN or tripterygium were
      able to inhibit these changes (all P<0.01). It was speculated that TSRDN may
      prevent angiogenesis by inhibiting the expression of STAT3 and the DNA-binding
      activity of NF-kappaB p65, thereby potentially improving CIA.

PMID- 27698705
TI  - Increased soluble and membrane-bound PD-L1 contributes to immune regulation and
      disease progression in patients with tuberculous pleural effusion.
AB  - Soluble and membrane-bound programmed death ligand-1 (sPD-L1 and mPD-L1,
      respectively) have been demonstrated to participate in the immune suppression of
      non-small cell lung cancer. However, the contribution of sPD-L1 and mPD-L1 to
      immune regulation and disease progression in patients with pleural effusions
      remains unknown. The present study evaluated the levels of sPD-L1 and membrane
      bound PD-1/PD-L1 in the peripheral blood and pleural effusions of patients with
      tuberculous pleural effusion (TPE), malignant pleural effusion (MPE) and non
      tuberculous non-malignant pleural effusion (n-TB n-M). Furthermore, selected T
      lymphocytes and cluster of differentiation (CD)14+ monocytes were co-cultured to
      investigate the potential effect of the PD-1/PD-L1 pathway in TPE. Levels of sPD
      L1 and PD-L1 on CD14+ monocytes were increased in the TPE group, as compared with
      the MPE and n-TB n-M groups. Furthermore, sPD-L1 levels and the expression levels
      of PD-L1 on CD14+ monocytes were demonstrated to be positively correlated with
      interferon (IFN)-gamma concentration in pleural effusions. Therefore, IFN-gamma
      may increase the expression of PD-L1 on CD14+ monocytes in vitro. Cell counting
      kit-8 analysis demonstrated that anti-PD-L1 antibody was able to partially
      reverse the proliferation of T lymphocytes in the co-culture system. The results
      of the present study indicated that sPD-L1 or mPD-L1 are associated with the
      immune regulation and disease progression of TPE, and may serve as possible
      biomarkers of TPE. Furthermore, sPD-L1 and the PD-1/PD-L1 pathway of TPE may be
      associated with the Th1 immune response; therefore, an anti-PD-1/PD-L1 pathway
      suggests a potential immune therapy strategy for the treatment of TPE.

PMID- 27698706
TI  - Sulfated polysaccharide-protein complex sensitizes doxorubicin-induced apoptosis
      of breast cancer cells in vitro and in vivo.
AB  - The present study aimed to investigate the effect of sulfated polysaccharide
      protein complex (SPPC) on the antitumor effect of doxorubicin (Dox) on MDA-MB-231
      breast cancer cells in vitro and in vivo. MTT and Annexin V/propidium iodide
      staining assays demonstrated that SPPC selectively sensitized MDA-MB-231 cells to
      Dox-induced cytotoxicity. The half maximal inhibitory concentration of Dox
      against MDA-MB-231 cells was decreased from 5.3 to 1.5 uM when it was used
      concomitantly with 5 uM SPPC. SPPC potentiated Dox-induced apoptosis in breast
      cancer cells via the mitochondrial apoptosis signaling pathway by activating
      caspase-3 and caspase-9. Notably, the caspase inhibitor Z-VAD-fmk diminished the
      effect of SPPC on Dox-mediated apoptosis. Furthermore, combination treatment with
      SPPC and Dox markedly reduced the growth of breast cancer xenografts in mice. The
      present study demonstrated that SPPC was able to enhance the antitumor effect of
      Dox on breast cancer cells, thus suggesting that SPCC may be used to reduce the
      cumulative dose of Dox and its associated toxicities in the chemotherapy of
      breast cancer and other types of cancer.

PMID- 27698707
TI  - Acetylsalicylic acid combined with diclofenac inhibits cartilage degradation in
      rabbit models of osteoarthritis.
AB  - The present study aimed to investigate the effect of different concentrations of
      acetylsalicylic acid combined with diclofenac on the articular cartilage of a
      rabbit model of osteoarthritis (OA). A total of 40 New Zealand white rabbits were
      divided into 5 groups. Group A was a sham-operated control group, which was
      treated with normal saline. Groups B-E were OA models and were treated with
      normal saline and acetylsalicylic acid combined with diclofenac at concentrations
      of 5, 10 and 20 mg/kg, respectively. A cartilage macroscopic examination and a
      pathological observation were performed to analyze the structure of the articular
      cartilage in all of the treated groups. The nitric oxide (NO) content and
      interleukin 1beta (IL-1beta) levels were detected by an enzyme-linked
      immunosorbent assay. In addition, the protein expression of matrix
      metalloproteinase 3 (MMP)-3 and MMP-13 were detected by western blot analysis.
      The mRNA expression of tissue inhibitor of metalloproteinases 1 (TIMP1) was
      detected by polymerase chain reaction (PCR). The results revealed that different
      concentrations of the drugs significantly reduced the scores of cartilago
      articularis, the NO and IL-1beta levels and the protein expression of MMP-3 and
      MMP-13. Furthermore, PCR revealed that the mRNA expression of TIMP1 was
      significantly upregulated, and the effects increased with increasing drug
      concentration. Thus, the administration of different concentrations of
      acetylsalicylic acid combined with diclofenac demonstrates preventive or
      therapeutic effects against OA progression.

PMID- 27698708
TI  - Branch retinal artery occlusion following carotid stenting: A case report.
AB  - A 70 year old male was diagnosed with carotid stenosis and underwent carotid
      artery stenting (CAS). Severe postoperative complications arose subsequent to the
      procedure, including decreased visual acuity and symptoms of a visual field
      defect, and the patient was eventually diagnosed with retinal artery embolism.
      CAS reduces carotid plaque; however, the subsequent shedding of carotid plaque
      may cause retinal artery embolism, resulting in the serious loss of visual
      function in patients. This complication is of paramount importance and requires
      great consideration from the neurologist and the patients undergoing CAS.
      Ophthalmic evaluation is paramount following CAS due to the possibility of
      embolic occlusion of the retinal artery. It is imperative that patients be
      informed of the risk of permanent vision loss as a result of CAS.

PMID- 27698709
TI  - Rotavirus-associated immune thrombocytopenic purpura in children: A retrospective
      study.
AB  - Certain studies have previously indicated that an association may exist between
      rotavirus infection and primary immune thrombocytopenic purpura (ITP). The
      present retrospective study aimed to investigate whether rotavirus may cause ITP
      in children. Firstly, the incidence of ITP in children with or without rotavirus
      diarrhea was compared. A 14.58% incident rate was observed in children with
      rotavirus diarrhea compared with a 7.22% incident rate in children without
      rotavirus diarrhea. Subsequently, the clinical features of ITP children with or
      without rotavirus infection were compared. The results indicated that ITP
      children with rotavirus infection were significantly younger, showed
      significantly decreased mean platelet volume (MPV) levels and presented a
      significantly higher frequency of bleeding score of 3 against ITP children
      without rotavirus infection. In conclusion, these findings suggest that rotavirus
      serves a causative role in ITP.

PMID- 27698710
TI  - Decorin inhibits the proliferation of HepG2 cells by elevating the expression of
      transforming growth factor-beta receptor II.
AB  - The aim of the present study was to investigate the effects of decorin (DCN) on
      the proliferation of human hepatoma HepG2 cells and the involvement of
      transforming growth factor-beta (TGF-beta) signaling pathway. A vector containing
      DCN was transfected into HepG2 cells with the use of Lipofectamine 2000. Cell
      proliferation was assessed with an MTT assay, and western blot analysis was used
      to detect the protein expression of TGF-beta receptor I (TGF-betaRI),
      phosphorylated TGF-betaRI, p15 and TGF-betaRII. In addition, small interfering
      RNA (siRNA) silencing was performed to knock down the target gene. The results
      indicated that, compared with the control group, cell proliferation was
      significantly decreased in HepG2 cells transfected with DCN. In addition, DCN
      transfection significantly increased the phosphorylation level of TGF-betaRI in
      HepG2 cells. The expression of the downstream factor p15 was also significantly
      elevated in the DCN-transfected HepG2 cells. Furthermore, DCN transfection
      significantly elevated the expression level of TGF-betaRII in HepG2 cells. By
      contrast, the silencing of TGF-betaRII significantly decreased the
      phosphorylation of TGF-betaRI in DCN-transfected HepG2 cells. In addition, TGF
      betaRII silencing abolished the effects of DCN on the proliferation of HepG2
      cells. In conclusion, DCN elevated the expression level of TGF-betaRII, increased
      the phosphorylation level of TGF-betaRI, enhanced the expression of p15, and
      finally inhibited the proliferation of HepG2 cells. These findings may contribute
      to the understanding of the role of DCN in the pathogenesis of hepatic carcinoma
      and assist in the disease treatment.

PMID- 27698711
TI  - Biological significance of PinX1 telomerase inhibitor in esophageal carcinoma
      treatment.
AB  - In the present study, to investigate the expression of PinX1 gene and its
      functional effects in human esophageal carcinoma (Eca)-109 cell line, expression
      vectors of human PinX1 (pEGFP-C3-PinX1) and its small interfering RNA (PinX1-FAM
      siRNA) were constructed and transfected into Eca-109 cells using Lipofectamine
      2000. Firstly, the mRNA expression level of PinX1 was examined using reverse
      transcription-polymerase chain reaction (RT-PCR). Once successful transfection
      was achieved, the effects on the mRNA level of human telomerase reverse
      transcriptase (hTERT), telomerase activity, cell proliferation and apoptosis were
      examined by semi-quantitative RT-PCR, stretch PCR, MTT assay and flow cytometry,
      respectively. Analysis of restriction and sequencing demonstrated that the
      recombining plasmids were successfully constructed. The results also indicated
      that transfection with pEGFP-C3-PinX1 and PinX1-FAM-siRNA into Eca-109 cells
      significantly increased PinX1 mRNA, decreased hTERT mRNA by 29.9% (P<0.05), and
      significantly reduced telomerase activity (P<0.05), inhibited cell growth, and
      increased the cell apoptotic index from 19.27+/-0.76 to 49.73+/-2%. The
      transfected PinX1-FAM-SiRNA exhibited PinX1 mRNA expression levels that were
      significantly decreased by 70% (P<0.05), whereas the remaining characteristics of
      Eca-109 cells, including cell growth, mRNA level of hTERT, telomerase activity
      and cell apoptotic index were not altered. Exogenous PinX1 has been demonstrated
      to be highly expressed in human Eca. PinX1 can inhibit human telomerase activity
      and the expression of hTERT mRNA, reduce tumor cell growth and induce apoptosis.
      Notably, these inhibitory functions were inhibited by silencing PinX1 in Eca with
      PinX1-FAM-siRNA. PinX1 was successfully increased and decreased in the present
      study, demonstrating that it may be a potential telomerase activity inhibitor. As
      PinX1 is an endogenous telomerase inhibitor, it may be used as a novel tumor
      targeted gene therapy.

PMID- 27698713
TI  - C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia
      induced injury.
AB  - The optimal treatment for chronic intermittent hypoxia (CIH)-induced
      cardiovascular injuries has yet to be determined. The aim of the current study
      was to explore the potential protective effect and mechanism of a C1 inhibitor in
      CIH in the myocardium. The present study used a rat model of CIH in which
      complement regulatory protein, known as C1 inhibitor (C1INH), was administered to
      the rats in the intervention groups. Cardiomyocyte apoptosis was detected by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The
      expression of proteins associated with the apoptotic pathway, such as B-cell
      lymphoma 2 (Bcl-2), Bax and caspase-3 were detected by western blot analysis. The
      expression of complement C3 protein and RNA were also analyzed. C1INH was
      observed to improve the cardiac function in rats with CIH. Myocardial
      myeloperoxidase activity, a marker of neutrophil infiltration, was significantly
      decreased in the C1INH intervention group compared with the CIH control group,
      and cardiomyocyte apoptosis was significantly attenuated (P<0.05). Western
      blotting and reverse transcription-polymerase chain reaction analysis indicated
      that the protein expression levels of Bcl-2 were decreased and those of Bax were
      increased in the CIH group compared with the normal control group, but the
      protein expression levels of Bcl-2 were increased and those of Bax were decreased
      in the C1INH intervention group, as compared with the CIH group. Furthermore, the
      CIH-induced expression and synthesis of complement C3 in the myocardium were also
      reduced in the C1INH intervention group. C1INH, in addition to inhibiting
      complement activation and inflammation, preserved cardiac function in CIH
      mediated myocardial cell injury through an anti-apoptotic mechanism.

PMID- 27698712
TI  - Gelatin sponge microparticles for the treatment of the spontaneous rupture of
      hepatocellular carcinoma hemorrhage.
AB  - Spontaneous rupture of hepatocellular carcinoma hemorrhage is life-threatening.
      The aim of the present study was to retrospectively analyze the effect of gelatin
      sponge microparticles (GSMs) of various diameters on the treatment of spontaneous
      rupture of hepatocellular carcinoma hemorrhage. GSMs serve as embolization agents
      by transcatheter arterial chemoembolization (TACE), and the current study
      analyzed their safety and efficacy. Data from a total of 13 cases of spontaneous
      rupture of hepatocellular carcinoma hemorrhage, who were treated with GSM-TACE at
      the Affiliated Zhongshan Hospital of Dalian University (Dalian, China) between
      August 2010 and June 2014, were collected. Post-operative complications were
      classified according to the National Cancer Institute Common Terminology
      Criteria. Review computed tomography was conducted 1, 3 and 6 months after GSM
      TACE treatment in order to determine the occurrence of re-bleeding; the tumor
      response was evaluated based on the Modified Response Evaluation Criteria In
      Solid Tumors and the expression levels of alpha-feroprotein. The patients were
      followed-up for 1-6 months (average, 5.15+/-1.67 months). Following GSM-TACE
      treatment, 13 cases reached successful hemostasis without technical
      complications. The survival rates 1, 3 and 6 months after treatment were 76.9
      (10/13), 61.5 (8/13) and 53.8% (7/13), respectively; the objective response rates
      were 61.6, 53.9 and 38.5%, respectively. The primary post-operative complications
      were pain (100%), nausea and vomiting (69.2%), and fever (53.8%). Among the 13
      patients, 2 cases underwent surgical excision 10 and 30 days after GSM-TACE, and
      1 case experienced re-bleeding 3 months after treatment, after which the patient
      received a second treatment with TACE and successful achieved hemostasis. In
      conclusion, GSM-TACE of various diameters is a safe and effective method in the
      treatment of spontaneous rupture of hepatocellular carcinoma hemorrhage. GSM-TACE
      is able to achieve immediate hemostasis and improves the survival rate of
      patients, thus creating favorable conditions for follow-up treatment.

PMID- 27698714
TI  - Diagnostic values of red cell distribution width, platelet distribution width and
      neutrophil-lymphocyte count ratio for sepsis.
AB  - The aim of this study was to evaluate the diagnostic efficiency of red blood cell
      distribution width (RDW), platelet distribution width (PDW), the neutrophil
      lymphocyte count ratio (NLCR), procalcitonin (PCT) and C-reactive protein (CRP)
      for the prediction of sepsis. A total of 120 consecutive patients who underwent
      blood culture testing were included. The PCT and CRP levels, and RDW, PDW and
      NLCR percentages were determined and compared between patients with positive
      blood cultures and those without. The PCT, CRP, RDW, PDW and NLCR values were
      significantly higher in patients with positive blood culture compared with those
      without. PCT and NLCR each had a high diagnostic performance for the prediction
      of sepsis, with an area under the curve (AUC) for sepsis of 0.829 and 0.718,
      respectively. A combination of RDW, PDW and NLCR also exhibited a good diagnostic
      performance for sepsis (AUC, 0.704). NLCR is easily obtained by automated
      hematological analysis. Moreover, NLCR was found to have a high diagnostic
      efficiency for the prediction of sepsis, with greater sensitivity and accuracy
      than CRP. In conclusion, PCT exhibited the optimal diagnostic performance among
      the tested markers. The combination of the three parameters of RDW, PDW and NLCR,
      demonstrated a high diagnostic performance similar to that of PCT.

PMID- 27698715
TI  - Microarray analysis reveals altered circulating microRNA expression in mice
      infected with Coxsackievirus B3.
AB  - Coxsackievirus B3 (CVB3) is a common causative agent in the development of
      inflammatory cardiomyopathy. However, whether the expression of peripheral blood
      microRNAs (miRNAs) is altered in this process is unknown. The present study
      investigated changes to miRNA expression in the peripheral blood of CVB3-infected
      mice. Utilizing miRNA microarray technology, differential miRNA expression was
      examined between normal and CVB3-infected mice. The present results suggest that
      specific miRNAs were differentially expressed in the peripheral blood of mice
      infected with CVB3, varying with infection duration. Using miRNA microarray
      analysis, a total of 96 and 89 differentially expressed miRNAs were identified in
      the peripheral blood of mice infected with CVB3 for 3 and 6 days, respectively.
      Quantitative polymerase chain reaction was used to validate differentially
      expressed miRNAs, revealing a consistency of these results with the miRNA
      microarray analysis results. The biological functions of the differentially
      expressed miRNAs were then predicted by bioinformatics analysis. The potential
      biological roles of differentially expressed miRNAs included hypertrophic
      cardiomyopathy, dilated cardiomyopathy and arrhythmogenic right ventricular
      cardiomyopathy. These results may provide important insights into the mechanisms
      responsible for the progression of CVB3 infection.

PMID- 27698716
TI  - Fulminant bilateral acute retinal necrosis syndrome associated with viral
      encephalitis: A case report.
AB  - Herpes simplex virus (HSV) is the most common cause of acute viral encephalitis.
      Acute retinal necrosis (ARN) is a rapidly progressing and potentially blinding
      eye disease that may be induced by HSV. The present case study reports the very
      rare case of a patient with herpes simplex encephalitis (HSE) combined with acute
      retinal necrosis (ARN). A 47-year-old woman was admitted to hospital with
      persistent high fever and somnolence for 5 days. Magnetic resonance imaging
      showed abnormal signals in the right medial temporal lobes, and HSV-1 was
      identified in the serum and cerebrospinal fluid. Five days later, despite
      treatment with intravenous acyclovir and partial improvement in consciousness,
      the patient suddenly developed blurred vision and bilateral visual pain. Fundus
      fluorescence angiography revealed bilateral vessel obstruction and flaky reduced
      fluorescence. ARN was diagnosed clinically. Dexamethasone was administered as an
      anti-inflammatory adjunct to intravenous acyclovir therapy. The visual acuity of
      the patient was reduced to mere light perception a further 4 days later. The
      present case indicates that HSE may be complicated with ARN, causing a reduction
      in visual acuity to mere light perception within a very short time.

PMID- 27698718
TI  - Mediastinal syndrome: A report of three cases.
AB  - Mediastinal syndromes are a group of disorders involving the anatomical
      structures of the mediastinum. An increase in the incidence of this syndrome has
      been observed following the widespread use of diagnostic imaging. In the present
      study, three different cases of mediastinal syndrome, one of which was
      complicated by superior vena cava syndrome, are discussed. The treatment in the
      three cases was dependent on the etiology. While a patient with goiter
      experienced resolution of the symptoms following thyroidectomy, and a patient
      with lymphoma experienced beneficial effects following medical treatment, the
      patient with lymph node metastasis caused by a gastric tumor succumbed to the
      disease. In conclusion, the present case reports demonstrated that mediastinal
      syndrome is a life threatening condition whose prognosis depends on the
      underlying cause.

PMID- 27698717
TI  - Tissue injuries after single-port and multiport laparoscopic gynecologic
      surgeries: A prospective multicenter study.
AB  - The present study focused on the degree of tissue injury following single-port
      laparoscopic surgery (SPLS) and multiport laparoscopic surgery (MPLS) for the
      treatment of various benign gynecologic diseases. A total of 228 patients were
      prospectively enrolled at seven academic centers in South Korea between April
      2011 and September 2012. Of these, 122 patients underwent SPLS and 106 patients
      underwent MPLS. The serum levels of C-reactive protein, creatine phosphokinase,
      lactic dehydrogenase and cancer antigen 125 were measured preoperatively and on
      postoperative day 4 by immunonephelometry. Cosmetic satisfaction and
      postoperative pain scores (visual analogue scale) were analyzed. Postoperative
      changes in the levels of the serum markers were found to be similar between the
      SPLS and MPLS groups. However, the postoperative pain scores at 48 h were
      significantly lower in the SPLS group when compared with those in the MPLS
      (P=0.001). In addition, patient-controlled analgesia was used more frequently by
      patients in the MPLS group (P=0.003). The present study is the first prospective
      investigation of tissue injury resulting from SPLS and MPLS in gynecology. In
      conclusion, the current study demonstrated that serum marker levels during SPLS
      were similar to those during MPLS in the treatment of benign gynecologic
      diseases. However, SPLS is a reasonable alternative to MPLS and is associated
      with comparable tissue injury, improved cosmesis and reduced postoperative pain.

PMID- 27698719
TI  - Endothelium-dependent and-independent relaxation induced by resveratrol in rat
      superior mesenteric arteries.
AB  - Resveratrol (Res) is a specific agonist of sirtuin 1, and has many
      cardioprotective effects. Although Res is able to relax various vascular beds,
      its pharmacological properties in rat superior mesenteric arteries and the
      underlying mechanism are not well clarified. The aim of present study was to
      investigate the vasorelaxant effects of Res on rat superior mesenteric arteries
      and the mechanisms involved. The isometric tension of rat superior mesenteric
      arterial rings was recorded in vitro using myography. It was found that Res
      concentration-dependently relaxed endothelium-intact superior mesenteric artery
      rings pre-contracted by phenylephrine hydrochloride (Emax, 97.66+/-0.79%; pD2,
      4.30+/-0.14) or KCl (Emax, 101.3+/-0.6%; pD2, 4.12+/-0.03). The vasorelaxant
      effect of Res on the superior mesenteric artery rings was partially endothelium
      dependent. NG-nitro-L-arginine methyl ester (100 uM) significantly inhibited the
      Res-induced vasorelaxant effect. However, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin
      1-one (10 uM) and indomethacin (5 uM) each had no effect on the Res-induced
      vasorelaxation. In artery rings without endothelium, the vasorelaxation induced
      by Res was attenuated by 4-aminopyridine (100 uM) and glibenclamide (10 uM).
      However, barium chloride dehydrate (10 uM) and tetraethylammonium chloride (1 mM)
      did not affect the vasorelaxation induced by Res. Moreover, Res also inhibited
      the contraction induced by an increase in external calcium concentration in Ca2+
      free medium plus KCl (60 mM). These results suggest that Res induces relaxation
      in superior mesenteric arterial rings through an endothelium-dependent pathway,
      involving nitric oxide release, and also through an endothelium-independent
      pathway, with opening of voltage-dependent K+ channels and ATP-sensitive K+
      channels and blockade of extracellular Ca2+ influx.

PMID- 27698720
TI  - Homocysteine injures vascular endothelial cells by inhibiting mitochondrial
      activity.
AB  - The aim of the present study was to investigate the role of homocysteine (Hcy) in
      the pathogenesis of pulmonary embolism (PE) and the associated molecular
      mechanisms in human umbilical vein endothelial cells (HUVECs). Hcy contents were
      detected with high-performance liquid chromatography. Apoptosis was detected by
      flow cytometry using Annexin-V staining. Cytochrome c oxidase (COX) activity was
      assessed with an enzyme activity assay, and the expression levels of COX 17 were
      determined by western blot analysis. Intracellular reactive oxygen species levels
      were measured using a microplate reader with a fluorescence probe. The results
      demonstrated that, compared with the control group, the serum Hcy levels were
      significantly elevated in the PE group, suggesting that Hcy may be an indicator
      for PE. Following treatment with Hcy, the apoptosis rate was markedly elevated in
      HUVECs. Moreover, Hcy decreased COX activity and downregulated the expression of
      COX 17 in HUVECs. Furthermore, Hcy increased the ROS levels in these endothelial
      cells. However, all the above-mentioned physiopathological changes induced by Hcy
      in HUVECs could be restored by folic acid. In conclusion, the results of the
      present study demonstrated that Hcy inhibited COX activity, downregulated COX 17
      expression, increased intracellular ROS levels and enhanced apoptosis in
      endothelial cells.

PMID- 27698721
TI  - siRNA-mediated silencing of phosphodiesterase 4B expression affects the
      production of cytokines in endotoxin-stimulated primary cultured microglia.
AB  - Phosphodiesterase 4 (PDE4) has four subtypes: PDE4A, PDE4B, PDE4C and PDE4D. The
      expression of PDE4 subtypes in microglial cells and the specific contribution of
      each subtype to inflammation remain unclear. In this study, the expression of
      PDE4 subtypes in primary microglial cells was assayed. Primary microglial cells
      were then transfected with specific small interfering RNA (siRNA) against each
      PDE4 subtype. PDE4 subtype A-D knockdown was confirmed by quantitative polymerase
      chain reaction. Secreted cytokines in the supernatant and intracellular cyclic
      adenosine monophosphate (cAMP) levels of transfected cells were measured. The
      effect of PDE4B siRNA on the activation of extracellular regulated protein kinase
      (ERK) induced by lipopolysaccharide (LPS) in microglia was further tested by
      western blotting. Results showed that the primary microglial cells expressed all
      four types of PDE4s at the protein level. Transfection with the four siRNAs
      inhibited PDE4 subtype A-D mRNA expression, respectively. In primary microglial
      cells, treatment with PDE4B siRNA significantly inhibited the expression of tumor
      necrosis factor-alpha and interleukin (IL)-1beta, and enhanced the expression of
      cAMP, while siRNAs to other subtypes had no significant effects. However, none of
      the four siRNAs had any significant effect on the expression of IL-10.
      Furthermore, in the PDE4B group, the level of phosphorylated ERK was reduced.
      Among the four PDE4 subtypes, PDE4B plays an important role in regulating
      inflammatory responses in microglia, potentially through initially regulating the
      intracellular cAMP concentration.

PMID- 27698722
TI  - Analysis of the first therapeutic-target-achieving time of warfarin therapy and
      associated factors in patients with pulmonary embolism.
AB  - The present study aimed to investigate the factors affecting the first
      therapeutic-target-achieving (TTA) time of warfarin therapy in patients with
      acute pulmonary embolism (PTE). Between January 2008 and June 2013, patients with
      PTE confirmed by transpulmonary arterial enhanced computed tomographic pulmonary
      angiography or pulmonary ventilation perfusion scanning were included in the
      present study. Data collected included demographic information, history of
      tobacco and alcohol intake, basic diseases (stable and unstable hypertension,
      diabetes, heart failure, cancer/cerebral infarction, old myocardial infarction
      and atrial fibrillation), liver and kidney function, the haemoglobin and platelet
      count of the blood, international normalized ratio monitoring, warfarin dosage
      adjustment and medication combinations. Dynamic changes in international
      normalized ratio, anticoagulant efficacy, and adverse events within 90 days were
      monitored and analyzed. Univariate analysis demonstrated that the following
      factors affect the first TTA time: Initial dose, body mass index (BMI), liver
      function, heart failure, and the administration of levofloxacin, cephalosporins,
      and blood circulation-activating drugs. Logistic regression analysis revealed
      that the following were independent factors of the first TTA time: Initial dose,
      BMI, liver function, heart failure and levofloxacin. Therefore, the results of
      the present study demonstrated that various factors may affect the first TTA time
      of warfarin therapy, including the initial dose, BMI, liver function, heart
      function and concomitant medication.

PMID- 27698723
TI  - Role of nucleolar protein NOM1 in pancreatic islet beta cell apoptosis in
      diabetes.
AB  - Diabetes is a metabolic disease that results from impairment in insulin
      secretion. The present study aimed to investigate the potential role of NOM1 in
      the function of pancreatic islet beta cells and insulin secretion. MIN6 cells
      isolated from mice were transfected with siRNA-NOM1 to assess the influence of
      NOM1 on the expression of the cell apoptosis-associated proteins, such as caspase
      3. In addition, MIN6 cells were cultured in medium containing different glucose
      concentrations in order to assess the sensitivity of MIN6 cells to glucose. The
      effect of NOM1 expression and glucose on MIN6 cell proliferation was also
      analyzed using an MTT assay. Furthermore, the mRNA expression levels of insulin 1
      and 2 in MIN6 cells were detected using reverse transcription-quantitative
      polymerase chain reaction, while the expression levels of various cell apoptosis
      associated proteins, Bcl-2 and Bax, were analyzed using western blot analysis.
      Compared with the control group, downregulation NOM1 and high glucose
      concentration of 25 mM significantly increased the cleaved caspase-3 level in
      MIN6 cells (P<0.05). In addition, downregulation of NOM1 significantly inhibited
      the MIN6 cell proliferation ability and reduced the insulin 2 mRNA expression
      (P<0.05). NOM1 knockdown also resulted in significantly increased Bax2 level and
      decreased Bcl-2 level in MIN6 cells (P<0.05). However no significant difference
      in insulin mRNA expression was observed between the control and siRNA-NOM1
      transfected group (P>0.05). In conclusion, the present study suggested that NOM1
      expression may be affected by blood glucose, and that NOM1 may be associated with
      pancreatic islet beta cell apoptosis. In addition, NOM1 may serve a pivotal role
      in diabetes by affecting insulin synthesis and secretion in pancreatic islet beta
      cells.

PMID- 27698724
TI  - Clinical characteristics and analysis of familial oral lichen planus in eight
      Chinese families.
AB  - Oral lichen planus (OLP) is one of the most common oral mucosa diseases; however,
      familial OLP is uncommon. The present study reported and analyzed patients with
      familial OLP (n=18) in eight different Chinese families between January 1, 2012
      and December 31, 2013. Parameters analyzed include gender, age at diagnosis,
      lesion distribution and lesion type. The follow-up period for each patient was a
      minimum of 1 year. In this survey, 18/88 individuals in the eight families were
      affected. Females were more frequently affected, and the female to male ratio for
      familial OLP (2.2:1) was higher compared with that previously reported for
      nonfamilial OLP (1.4:1). The age at diagnosis, lesion distribution and lesion
      type showed consistency with reports concerning nonfamilial OLP, with the
      exception of family VI, in which 4/5 children had OLP/LP lesions and were of an
      early age at diagnosis. There were two families in which three generations had
      been affected by OLP. In addition, it appeared that patients of the same
      generation in the same family were of a similar age at diagnosis. No malignant or
      premalignant lesion was identified in the 18 individuals diagnosed with OLP from
      the eight families. The present study supports the hypothesis that genetic
      predisposition may serve a role in the etiology of OLP.

PMID- 27698725
TI  - Assessment of myocardial viability with delayed-enhancement MRI in coronary
      artery disease: A correlative study with coronary artery stenosis using digital
      subtraction angiography.
AB  - The aim of the present study was to investigate the correlation between the
      degree of coronary artery stenosis determined by digital subtraction angiography
      (DSA) and infarcted segments detected by delayed enhancement magnetic resonance
      imaging (DE-MRI). DE-MRI and DSA were performed in 40 patients with coronary
      artery disease. The number of myocardial segments with infarction, the transmural
      extent of myocardial infarction, score of myocardial infarction by MRI, degree of
      coronary artery stenosis and Gensini score of the coronary artery were assessed.
      The correlation was analyzed using Spearman's rank correlation test. Among the 40
      patients, 126 infarcted myocardial segments with a total score of 307 were found
      by DE-MRI; the total Gensini score for coronary artery stenosis was 587. It was
      observed that 81.74% of the infarcted segments were at sites with >50% coronary
      artery stenosis. The correlation coefficient between the Gensini score and
      myocardial infarction score was 0.786 (P<0.001), indicating a good correlation.
      However, 18.26% of myocardial infarction segments were found in patients with
      slight coronary artery stenosis (<=25%). A correlation was identified between DSA
      detected coronary artery stenosis and infarcted segments detected by DE-MRI; a
      higher transmural extent of myocardial infarction correlated with more severe
      stenosis of the coronary artery. The combined use of the two tools may facilitate
      accurate diagnosis.

PMID- 27698726
TI  - Evaluation of the effects of ketamine on spinal anesthesia with levobupivacaine
      or ropivacaine.
AB  - Spinal anesthesia or regional anesthesia is a potent anesthetic procedure.
      Additional modalities have been sought to increase the duration of block in
      spinal anesthesia. Ketamine is an N-methyl-D-aspartate (NMDA) receptor blocker
      that has an anesthetic effect when injected intrathecally and has a synergic
      effect with bupivacaine. Ketamine also has potent analgesic properties. The
      present study investigated the effect of intrathecally administered ketamine on
      spinal anesthesia with levobupivacaine or ropivacaine. Sprague-Dawley rats at
      post-natal day 21 were exposed to spinal anesthesia with 0.5% levobupivacaine or
      0.5% ropivacaine. Separate groups of rats were treated with intrathecal ketamine
      at a 5 or 10 mg/kg bodyweight dose along with ropivacaine or levobupivacaine. The
      thermal and mechanical withdrawal latencies of the animals were determined using
      hot plate and von Frey filaments, respectively. A rotarod apparatus was employed
      to assess the capacity of the rats to rotate the spindle at 24 h following
      anesthesia. The gait of the rat pups was also assessed. Intrathecal
      administration of ketamine resulted in dense blocks and extended the duration of
      spinal blocks as evidenced by thermal latencies and responses to von Frey
      filaments. The latency to fall was shorter in rats exposed to ketamine along with
      ropivacaine or levobupivacaine spinal anesthesia. The gait parameters were also
      more disturbed upon ketamine administration. In conclusion, ketamine
      administration with ropivacaine or levobupivacaine increased the intensity and
      duration of spinal blockade, thereby increasing the anesthetic effects.

PMID- 27698727
TI  - Partial response to imatinib treatment in a patient with unresectable
      gastrointestinal stromal tumor: A case report and mini literature review.
AB  - The aim of the present study was to evaluate the efficacy and safety of imatinib
      mesylate in unresectable gastrointestinal stromal tumor (GIST) and to discuss its
      therapeutic regimen. A patient with unresectable GIST is described, and several
      key clinical studies are reviewed, including the clinical trials B2222 and S0033,
      which contain recently reported results of the long-term clinical outcome of
      imatinib in patients with unresectable or metastatic GIST. The recent results of
      the two studies demonstrate the long-term efficacy and safety of imatinib for
      unresectable or metastatic GIST. A positive response to imatinib treatment was
      observed in the present patient, which is consistent with the data of the B2222
      and S0033 trials. However, further long-term, large-scale, multicenter and
      controlled trials are required to determine the relative efficacy of combining
      imatinib agents with surgical procedures or administering imatinib alone.

PMID- 27698728
TI  - Influencing factors of transient elastography in detecting liver stiffness.
AB  - Liver stiffness, which correlates well with liver fibrosis stage, can be measured
      noninvasively by transient elastography, also known as Fibroscan. The present
      study aimed to determine the independent factors influencing Fibroscan detection
      by multiple regression analysis. A total of 181 patients who required liver
      biopsy were enrolled. Liver stiffness measurement (LSM) was detected by Fibroscan
      on the day of liver biopsy, while clinical information and routine biochemical
      examination results were also collected. Correlation was analyzed by Spearman's
      correlation, and multiple regression analysis was performed to analyze the
      independent influencing factors. The results demonstrated that platelet (PLT)
      levels, serum albumin (ALB), prothrombin activity (PTA) and body mass index (BMI)
      were independent predictors of liver stiffness. The contribution of these four
      predictors to the regression equation was in the following descending order: PLT
      (negative correlation) > ALB (negative correlation) > PTA (negative correlation)
      > BMI (positive correlation). In conclusion, the parameters of PLT, ALB, PTA and
      BMI are independent predicting factors affecting Fibroscan detection. Therefore,
      the diagnosis and evaluation of liver fibrosis should comprehensively consider
      the results of Fibroscan, and clinical and laboratory examinations.

PMID- 27698729
TI  - Triptolide inhibits the progression of atherosclerosis in apolipoprotein E-/-
      mice.
AB  - Atherosclerosis, the major cause of cardiovascular disease, is accompanied by a
      chronic inflammatory response during the disease. Triptolide (TPL) is an active
      natural compound that has been demonstrated to possess anti-inflammatory
      activities in various cell types. However, the effects of TPL on atherosclerosis
      have not yet been studied. The goal of the present study was to determine the
      effects of TPL on apolipoprotein E knock-out (ApoE-/-) mice fed with a high-fat
      diet and to analyze the changes in lipid metabolism and inflammatory cytokines to
      clarify the underlying molecular mechanisms. Firstly, the genotypes of ApoE-/-
      mice and corresponding wild-type mice were identified using polymerase chain
      reaction. The ApoE-/- mice were randomly divided into four groups: ApoE-/- model
      mice, and ApoE-/- mice treated with 25, 50 or 100 ug/kg TPL every twice day. Wild
      type mice with the same genetic background constituted the fifth group. The mice
      in each group were given a high-fat diet from week 8 after birth until week 20.
      Total cholesterol and total triglyceride levels were determined at 16 and 20
      weeks. The results demonstrated that the levels of total cholesterol and total
      triglyceride in the plasma were highly increased in ApoE-/- mice models, compared
      with those of wild-type mice, and the ApoE-/- mice treated with TPL had decreased
      levels of total cholesterol and total triglyceride in plasma, which exhibited a
      dose-dependent reduction as the dose of TPL increased. Moreover, the effects of
      TPL on the production of inflammatory cytokines in macrophages were determined by
      ELISA. The results demonstrated that the macrophages from ApoE-/- mice produced
      high levels of the inflammatory cytokines tumor necrosis factor-alpha,
      interleukin (IL)-1beta, IL-6 and IL-8. However, following treatment with TPL
      doses of 25, 50 and 100 ug/kg, the cytokine levels were significantly decreased
      in a dose-dependent manner. Additionally, proteins associated with lipid
      metabolism were tested by western blotting. The results showed that the
      expression of anti-ATP-binding cassette transporter A1 in the macrophages of ApoE
      /- mice was increased following treatment with TPL. However, the expression
      levels of LXRalpha were not markedly changed following treatment of the mice with
      different doses of TPL. These results suggest that TPL inhibited the progression
      of atherosclerosis not only by inhibiting the chronic inflammatory response, but
      also by regulating lipid metabolism, which may provide new insights useful in the
      clinical therapy of atherosclerosis.

PMID- 27698730
TI  - Surgical treatment of incarcerated calculi via laparoscopic bile duct exploration
      using laparotomy biliary lithotomy forceps.
AB  - The present study aimed to investigate the practicability and clinical value of
      applying laparotomy biliary lithotomy forceps to laparoscopic bile duct
      exploration (LCBDE) for the surgical treatment of incarcerated calculi. A total
      of 63 patients were diagnosed with cholecystolithiasis and choledocholithiasis.
      The present study performed a retrospective analysis of clinical samples from 16
      of these patients who had incarcerated calculi at the terminus of the common bile
      duct, and who had been treated with laparoscopic cholecystectomy and LCBDE.
      During the procedure, laparotomy biliary lithotomy forceps were used to gently
      remove the calculi from the common bile duct. Of the surgical procedures that
      used laparotomy biliary lithotomy forceps, one case was unsuccessful and 15 cases
      were successful. The results of the present study suggested that it may be
      clinically advisable to use laparotomy biliary lithotomy forceps to remove
      incarcerated calculi from the common bile duct during a laparoscopy, since it is
      easy, economical and effective.

PMID- 27698731
TI  - Quality evaluation of Heshouwu, a Taoist medicine in Wudang, China.
AB  - Polygonum multiflorum Thunb., which is known as Heshouwu in China, is a Taoist
      medicine sourced from the Wudang mountain area. At present, the quality of the
      Heshouwu sourced from this region is unknown. The present study aimed to evaluate
      the quality of wild Heshouwu collected from the Wudang mountain area,
      particularly the 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG) and
      combined anthraquinone (CAQ) content, compared with that of commercially
      available Heshouwu. Furthermore, the potential quantities of organic pesticide
      residues were determined. High performance liquid chromatography with a diode
      array detector was used to quantify TSG and CAQ content, whereas gas
      chromatography (GC), performed using a temperature gradient, was used to detect
      the presence of organochlorine, pyrethroid and organophosphorus pesticides. The
      average TSG content present in the wild Heshouwu from the Wudang mountain area
      and in the commercially available Heshouwu was 2.39 and 1.10%, respectively. In
      addition, the average content of CAQ in these was 1.41 and 3.46%, respectively.
      GC did not detect residues of organic pesticides in the wild Heshouwu, thus this
      plant met the criterion of the Chinese Pharmacopeia (2010 edition). The results
      of the present study indicated that wild Heshouwu from the Wudang mountain area
      may be suitable for use as a Chinese medicine across China.

PMID- 27698732
TI  - Recombinant expression and biological characterization of the antimicrobial
      peptide fowlicidin-2 in Pichia pastoris.
AB  - Fowlicidins are a group of cathelicidin antimicrobial peptides that were
      initially identified in chickens. Fowlicidin-2, which is composed of 31 amino
      acids, is widely expressed in the majority of tissues in chickens and has an
      important role in innate immunity. In the present study, a recombinant expression
      system for fowlicidin-2 was successfully constructed using Pichia pastoris X-33
      and the expression vector pPICZalpha-A. Under the optimized fermentation
      conditions, 85.6 mg fowlicidin-2 with >95% purity was obtained from 1 liter
      culture medium following purification by ion exchange chromatography and reversed
      phase high performance liquid chromatography. The recombinant fowlicidin-2
      exhibited broad spectrum antimicrobial activity and had a minimum inhibitory
      concentration ranging from 1 to 4 uM. Furthermore, recombinant fowlicidin-2
      exhibited hemolytic activity, promoting 50% human erythrocyte hemolysis in the
      concentration range of 128-256 uM, and anticancer activity, resulting in the
      death of 50% of A375 human malignant melanoma cells in the concentration range of
      2-4 uM. The results of the present study suggest that recombinant fowlicidin-2
      may be a promising candidate for therapeutic applications.

PMID- 27698733
TI  - Role of PiCCO monitoring for the integrated management of neurogenic pulmonary
      edema following traumatic brain injury: A case report and literature review.
AB  - Neurogenic pulmonary edema (NPE) is occasionally observed in patients with
      traumatic brain injury (TBI); however, this condition is often underappreciated.
      NPE is frequently misdiagnosed due to its atypical clinical performance, thus
      delaying appropriate treatment. A comprehensive management protocol of NPE in
      patients with TBI has yet to be established. The current study reported the case
      of a 67-year-old man with severe TBI who was transferred to our intensive care
      unit (ICU). On day 7 after hospitalization, the patient suddenly suffered
      tachypnea, tachycardia, systemic hypertension and hypoxemia during lumbar cistern
      drainage. Intravenous diuretics, tranquilizer and glucocorticoid were
      administered due to suspected left heart failure attack. Chest radiography
      examination supported the diagnosis of pulmonary edema; however, hypotension and
      hypovolemia were subsequently observed. Pulse index continuous cardiac output
      (PiCCO) hemodynamic monitoring and bedside echocardiography were performed, which
      excluded the diagnosis of cardiac pulmonary edema, and thus the diagnosis of NPE
      was confirmed. Goal-directed therapy by dynamic PiCCO monitoring was then
      implemented. In addition, levosimendan, an inotropic agent, was introduced to
      improve cardiac output. The patient had complete recovered from pulmonary edema
      and regained consciousness on day 11 of hospitalization. The current case
      demonstrated that PiCCO monitoring may serve a central role in the integrated
      management of NPE in patients with TBI. Levosimendan may be a potential medicine
      in treating cardiac dysfunction, along with its benefit from improving
      neurological function in NPE patients.

PMID- 27698734
TI  - C/EBP beta mRNA expression is upregulated and positively correlated with the
      expression of TNIP1/TNFAIP3 in peripheral blood mononuclear cells from patients
      with systemic lupus erythematosus.
AB  - CCAAT/enhancer-binding protein beta (C/EBP beta) has important roles in numerous
      signaling pathways. The expression of the majority of regulators and target gene
      products of C/EBP beta, including tumor necrosis factor alpha-induced protein 3
      (TNFAIP3) and TNFAIP3-interacting protein 1 (TNIP1), are upregulated in patients
      with systemic lupus erythematosus (SLE). The aim of the present study was to
      investigate whether C/EBP beta expression is associated with SLE pathogenesis and
      correlates with TNIP1 and TNFAIP3 expression. Quantitative reverse transcription
      polymerase chain reaction analysis was used to assess the expression of C/EBP
      beta, TNIP1, and TNFAIP3 mRNA in peripheral blood mononuclear cells (PBMC) from
      20 patients with SLE and 20 healthy controls. Spearman's rank test was used to
      determine the correlation between C/EBP beta expression and SLE disease activity,
      and that between C/EBP beta expression and TNIP1/TNFAIP3 expression in PBMCs from
      patients with SLE. C/EBP beta mRNA expression was markedly increased in patients
      with SLE compared with healthy controls. The expression of C/EBP beta was
      positively correlated with the SLE disease activity index and negatively
      correlated with the serum level of complement components C3 and C4. In addition,
      C/EBP beta mRNA expression was increased in PBMCs from SLE patients that were
      positive for antinuclear, anti-Smith and anti-nRNP antibodies, compared with the
      antibody negative SLE patients. Furthermore, the mRNA expression levels of C/EBP
      beta in patients with SLE was positively correlated with TNIP1 and TNFAIP3
      expression. The results of the current study suggest that the increased
      expression of C/EBP beta in PBMCs and the interaction between C/EBP beta and
      TNIP1/TNFAIP3 may be involved in the pathogenesis of SLE.

PMID- 27698736
TI  - Use of deep brain stimulation for major affective disorders.
AB  - The multifactorial etiology of major affective disorders, such as major
      depression and bipolar disorder, poses a challenge for identification of
      effective treatments. In a substantial number of patients, psychopharmacologic
      treatment does not lead to effective continuous symptom relief. The use of deep
      brain stimulation (DBS) for treatment-resistant patients is an investigational
      approach that has recently produced promising results. The recent development of
      safer stereotaxic neurosurgery, and the combination with functional neuroimaging
      to map the affected brain circuits, have led to the investigation of DBS as a
      potential strategy to treat major mood disorders. Several independent clinical
      studies have recently shown that chronic DBS treatment leads to remission of
      symptoms in a high number of treatment-resistant patients for major depression
      and bipolar disorder. In conclusion, the existing proof-of-principle that DBS can
      be an effective intervention for treatment-resistant depression opens new avenues
      for treatment. However, multicenter, randomized and blind trials need to confirm
      efficacy and be approved after the most recent failures. Patient selection and
      surgical-related improvements are key issues that remain to be addressed to help
      deliver more precise and customized treatment.

PMID- 27698735
TI  - Parasitic infection as a potential therapeutic tool against rheumatoid arthritis.
AB  - Parasites, which are a recently discovered yet ancient dweller in human hosts,
      remain a great public health burden in underdeveloped countries, despite
      preventative efforts. Rheumatoid arthritis is a predominantly cosmopolitan health
      problem with drastic morbidity rates, although encouraging progress has been
      achieved regarding treatment. However, although various types of methods and
      agents have been applied clinically, their broad usage has been limited by their
      adverse effects and/or high costs. Sustained efforts have been exerted on the
      'hygiene hypothesis' since the 1870s. The immunosuppressive nature of parasitic
      infections may offer potential insight into therapeutic strategies for rheumatoid
      arthritis, in which the immune system is overactivated. An increasing number of
      published papers are focusing on the preventive and/or curative effect of various
      parasitic infection on rheumatoid arthritis from experimental studies to large
      scale epidemiological studies and clinical trials. Therefore, the present review
      aimed to provide a general literature review on the possible beneficial role of
      parasitic infection on rheumatoid arthritis.

PMID- 27698738
TI  - Effectiveness of palliative care for non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer mortality worldwide. Despite increases
      in the survival rate for various types of cancer over the past several decades,
      lung cancer remains an overwhelmingly lethal disease and the majority of patients
      succumb to the disease in a short period of time. A number of treatment options
      are available depending on the stage of lung cancer. The present review focused
      on palliative care and is associated with stage IIIB and IV of non-small cell
      lung cancer (NSCLC). Stage IIIB disease is not amenable to curative treatment and
      for stage IV disease, treatment is palliative in nature, with a focus on
      increasing survival time, controlling symptoms and improving or maintaining
      quality of life. Palliative treatment options include chemotherapy, radiotherapy
      and supportive care. The present review examines the important aspects of
      palliative therapy with regard to NSCLC.

PMID- 27698737
TI  - Pediatric rhinitis risk factors.
AB  - Rhinitis is a common global disorder that impacts on the quality of life of the
      sufferer and caregivers. Treatment for pediatric rhinitis is empirical and does
      not include a detailed history of the allergy triggers or allergy testing. Thus,
      allergen avoidance advice is not tailored to the child's sensitivities, which may
      result in adenoid hypertrophy. However, infant onset rhinitis, especially its
      relationship with respiratory viruses, remains to be further clarified. Rhinitis
      basically involves inflammation of the upper nasal lining, presenting typically
      with symptoms of runny nose (rhinorrhea), nasal blockage, and/or sneezing. While
      not typically fatal, it does impose significant health, psychological, and
      monetary burden to its sufferers, and is thus considered a global health problem.
      Previous findings showed that immunotherapy had significant clinical efficacy in
      children with allergic rhinitis. The present review article aims to highlight
      recent perspectives pertaining to the rhinitis risk factors especially in
      pediatric patients.

PMID- 27698741
TI  - Hospital information technology in home care.
AB  - The utilization of hospital information technology (HIT) as a tool for home care
      is a recent trend in health science. Subjects gaining benefits from this new
      endeavor include middle-aged individuals with serious chronic illness living at
      home. Published data on the utilization of health care information technology
      especially for home care in chronic illness patients have increased enormously in
      recent past. The common chronic illnesses reported in these studies were
      primarily on heart and lung diseases. Furthermore, health professionals have
      confirmed in these studies that HIT was beneficial in gaining better access to
      information regarding their patients and they were also able to save that
      information easily for future use. On the other hand, some health professional
      also observed that the use of HIT in home care is not suitable for everyone and
      that individuals cannot be replaced by HIT. On the whole it is clear that the use
      of HIT could complement communication in home care. The present review aims to
      shed light on these latest aspects of the health care information technology in
      home care.

PMID- 27698739
TI  - Metabolic syndrome in children (Review).
AB  - Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors, including
      central obesity, insulin resistance, glucose intolerance, dyslipidemia and
      increased blood pressure. The prevalence of MetS is on the increase worldwide
      owing to the epidemic of overweight and obesity. The risk of prevalence of MetS
      greatly increases during adulthood for those children exposed to cardiometabolic
      risk factors in their early lives. MetS has also been associated with liver fat
      accumulation in children. Elevated levels of plasma alanine aminotransferase and
      gamma-glutamyl transferase have been associated with liver fat accumulation. The
      present review aimed to expand knowledge on the clustering of cardiometabolic
      risk factors responsible for the widespread occurrence of metabolic disease in
      children.

PMID- 27698740
TI  - Neurological teratogenic effects of antiepileptic drugs during pregnancy.
AB  - Epilepsy is one of the few neurologic disorders that requires a constant
      treatment during pregnancy. Epilepsy affects 0.3-0.8% of pregnant women.
      Prescription of antiepileptic drugs (AEDs) to pregnant women with epilepsy
      requires monitoring and maintaining a balance between limiting seizures and
      decreasing fetal exposure to the potential teratogenic effects. AEDs are also
      commonly used for psychiatric disorders, pain disorders, and migraines. The types
      of malformations that can result in fetuses exposed to AEDs include minor
      anomalies, major congenital malformations, intrauterine growth retardation,
      cognitive dysfunction, low IQ, microcephaly, and infant mortality. In the present
      review, we analyzed and summarized the current understanding of neurological
      development in fetuses that are exposed to various AEDs administered to pregnant
      epileptic women.

PMID- 27698742
TI  - Blood-filled cerebrospinal fluid-enhanced pericyte microvasculature contraction
      in rat retina: A novel in vitro study of subarachnoid hemorrhage.
AB  - Previously, it was widely accepted that the delayed ischemic injury and poor
      clinical outcome following subarachnoid hemorrhage (SAH) was caused by cerebral
      vasospasm. This classical theory was challenged by a clazosentan clinical trial,
      which failed to improve patient outcome, despite reversing angiographic
      vasospasm. One possible explanation for the results of this trial is the changes
      in microcirculation following SAH, particularly in pericytes, which are the
      primary cell type controlling microcirculation in the brain parenchyma. However,
      as a result of technical limitations and the lack of suitable models, there was
      no direct evidence of microvessel dysfunction following SAH. In the present
      study, whole-mount retinal microvasculature has been introduced to study
      microcirculation in the brain following experimental SAH in vitro. Artificial
      blood-filled cerebrospinal fluid (BSCF) was applied to the retinal
      microvasculature to test the hypothesis that the presence of subarachnoid blood
      affects the contractile properties of the pericytes containing cerebral
      microcirculation during the early phase of SAH. It was observed that BCSF induced
      retina microvessel contraction and that this contraction could be resolved by
      BCSF wash-out. Furthermore, BCSF application accelerated pericyte-populated
      collagen gel contraction and increased the expression of alpha-smooth muscle
      actin. In addition, BCSF induced an influx of calcium in cultured retinal
      pericytes. In conclusion, the present study demonstrates increased contractility
      of retinal microvessels and pericytes in the presence of BCSF in vitro. These
      findings suggest that pericyte contraction and microvascular dysfunction is
      induced following SAH, which could lead to greater susceptibility to SAH-induced
      ischemia.

PMID- 27698743
TI  - Systemic and local zoledronic acid treatment with hydroxyapatite bone graft: A
      histological and histomorphometric experimental study.
AB  - In this study, the aim was to compare the relative efficacy of systemic and local
      zoledronic acid (ZA) on a hydroxyapatite (HA) bone graft in a rat critical-size
      calvarial bone defect. In total, 84 female rats were divided into four groups:
      Empty control (EC) group with no treatment applied; HA group, in which only HA
      bone graft material was used in the calvarium; and HA plus local ZA (HA+LZA) and
      HA plus systemic ZA (HA+SZA) groups, in which animals received ZA locally or
      systemically, respectively, with HA bone graft material in the calvarium. A 5-mm
      standardised critical-size calvarial bone defect was created with a standard
      trephine drill and the respective treatment was applied. Rats were sacrificed 7,
      14 and 28 days later. The numbers of osteoclasts and osteoblasts, and degree of
      bone formation were evaluated histopathologically and histomorphometrically.
      Statistically significant differences were detected between the HA, HA+LZA and
      HA+SZA groups and the EC group for new bone formation (P<0.05). Osteoblast
      numbers in the HA+LZA and HA+SZA groups were significantly higher compared with
      those in the EC and HA groups (P<0.05). No statistically significant difference
      was detected between the HA+LZA and HA+SZA groups in new bone formation or
      osteoblast number (P>0.05). Bone formation was significantly higher in the HA
      group than in the EC group (P<0.05). The numbers of osteoclasts in the HA+LZA and
      HA+SZA groups were significantly higher than those in the groups EC and HA
      (P<0.05); however, there was no significant difference between groups HA+LZA and
      HA+SZA (P>0.05). Within the limitations of this study, systemic or local
      administration of ZA enhanced new bone formation with a HA bone graft in a rat
      critical-size calvarial defect model.

PMID- 27698744
TI  - Clinical evaluation of ultrasound screening in follow-up visits of infants with
      cerebral palsy at high risk for developmental dysplasia of the hip.
AB  - The aim of the study was to assess the clinical value of ultrasound screenings
      for the developmental dysplasia of the hip (DDH) and explore its etiology in high
      risk infants with cerebral palsy in follow-up visits. A group of 98 cases of
      infants at high-risk of cerebral palsy who received rehabilitation treatment
      between July, 2009 and July, 2010 were selected. Infants included 58 men and 40
      women, aged <6 months and not lost to follow-up visits. Ultrasound (using Graf
      static inspection) screening of hips was performed and the infants with
      abnormalities were given clinical intervention, and 1- to 2-year-old infants were
      given outpatient follow-ups. The results were analyzed and there were 40 abnormal
      cases among the 98 cases of infants at high risk of cerebral palsy, including 18
      cases of unstable hip joint, and 22 cases of DDH (12 cases of hip dysplasia, 3
      cases of hip subluxation and 7 cases of hip dislocation). Early clinical
      intervention for infants with hip dysplasia and outpatient follow up for infants
      aged 1-2 years was carried out and had ischemic necrosis of femoral head, with
      the exception of 1 case of femoral detorsion that was poorly restored. In
      conclusion, the probability of DDH was higher in infants at high-risk of cerebral
      palsy compared to the normal infants. Hip ultrasound is a safe, simple, and
      effective screening method for these infants, which is of great clinical
      significance for an earlier diagnosis and treatment of DDH in infants with
      cerebral palsy.

PMID- 27698745
TI  - Concomitant presentation of Anderson-Tawil syndrome and myasthenia gravis in an
      adult patient: A case report.
AB  - Andersen-Tawil syndrome (ATS) is an autosomal dominant, multisystem channelopathy
      characterized by periodic paralysis, ventricular arrhythmias and distinctive
      dysmorphic facial or skeletal features. The disorder displays marked
      intrafamilial variability and incomplete penetrance. Myasthenia gravis (MG) is an
      autoimmune disorder that demonstrates progressive fatigability, in which the
      nicotinic acetylcholine receptor (AChR) at neuromuscular junctions is the primary
      autoantigen. The present study reports a rare case of a 31-year-old woman with a
      history of morbid obesity and periodic weakness, who presented with hemodynamic
      instability, cardiogenic shock and facial anomalies. Laboratory results revealed
      hypokalemia and an elevated anti-AChR antibody expression levels.
      Electrocardiography demonstrated prolonged QT-interval, ST-elevation, and
      subsequent third-degree atrioventricular block. Neurological examination revealed
      bilateral ptosis, horizontal diplopia, dysarthria and generalized weakness. No
      mutations in the potassium channel inwardly rectifying subfamily J member 2 gene
      were detected in the present case. The patient was treated with oral potassium
      supplementation and an acetylcholinesterase inhibitor (pyridostigmine), after
      which the symptoms were improved. To the best of our knowledge, the present case
      report was the first to describe concomitant presentation of both ATS and MG,
      which represents a diagnostic and therapeutic challenge.

PMID- 27698746
TI  - Mesenchymal stem cells with irreversibly arrested proliferation stimulate decidua
      development in rats.
AB  - Stem cell transplantation, which is based on the application of mesenchymal
      stem/stromal cells (MSCs), is a rapidly developing approach to the regenerative
      therapy of various degenerative disorders characterized by brain and heart
      failure, as well as skin lesions. In comparison, the use of stem cell
      transplantations to treat infertility has received less attention. One of the
      causes of miscarriages and fetal growth delay is the loss of the decidual
      reaction of endometrial cells. The present study modeled decidualization
      processes in pseudopregnant rats. For cell transplantation experiments, the rats
      were transplanted with MSCs established from endometrial fragments in menstrual
      blood (eMSCs). These cells express common MSC markers, are multipotent and are
      able to differentiate into various tissue lineages. Cell therapy frequently
      requires substantial cell biomass, and cultivation of MSCs may be accompanied by
      significant changes to their properties, including malignant transformation. In
      order to minimize the potential for malignant transformation, the proliferation
      of eMSCs was irreversibly suppressed by irradiation and mitomycin C treatment.
      Transplantation of the rats with viable, non-proliferating eMSCs stimulated the
      development of all elements of decidual tissue. Conversely, transplantation of
      the rats with cells killed using 95% ethanol did not result in the development of
      decidual tissue. The present study demonstrated the potential for applying eMSCs
      to the cellular therapy of infertility associated with endometrial disorders
      characterized by decidualization insufficiency and implantation failure. In
      addition, the transplantation of viable but non-proliferating cells ensured that
      their oncogenic potential was limited.

PMID- 27698747
TI  - Co-expressed differentially expressed genes and long non-coding RNAs involved in
      the celecoxib treatment of gastric cancer: An RNA sequencing analysis.
AB  - The aim of the present study was to investigate the mechanisms of long non-coding
      RNAs (lncRNAs) in a gastric cancer cell line treated with celecoxib. The human
      gastric carcinoma cell line NCI-N87 was treated with 15 uM celecoxib for 72 h
      (celecoxib group) and an equal volume of dimethylsulfoxide (control group),
      respectively. Libraries were constructed by NEBNext Ultra RNA Library Prep kit
      for Illumina. Paired-end RNA sequencing reads were aligned to a human hg19
      reference genome using TopHat2. Differentially expressed genes (DEGs) and lncRNAs
      were identified using Cuffdiff. Enrichment analysis was performed using GO
      function package and KEGG profile in Bioconductor. A protein-protein interaction
      network was constructed using STRING database and module analysis was performed
      using ClusterONE plugin of Cytoscape. ATP5G1, ATP5G3, COX8A, CYC1, NDUFS3,
      UQCRC1, UQCRC2 and UQCRFS1 were enriched in the oxidative phosphorylation
      pathway. CXCL1, CXCL3, CXCL5 and CXCL8 were enriched in the chemokine signaling
      and cytokine-cytokine receptor interaction pathways. ITGA3, ITGA6, ITGB4, ITGB5,
      ITGB6 and ITGB8 were enriched in the integrin-mediated signaling pathway. DEGs co
      expressed with lnc-SCD-1:13, lnc-LRR1-1:2, lnc-PTMS-1:3, lnc-S100P-3:1, lnc
      AP000974.1-1:1 and lnc-RAB3IL1-2:1 were enriched in the pathways associated with
      cancer, such as the basal cell carcinoma pathway in cancer. In conclusion, these
      DEGs and differentially expressed lncRNAs may be important in the celecoxib
      treatment of gastric cancer.

PMID- 27698748
TI  - IL-35 improves Treg-mediated immune suppression in atherosclerotic mice.
AB  - Interleukin (IL)-35 is an anti-inflammatory cytokine that may have a protective
      role in atherosclerosis (AS). However, the exact role of IL-35 in the disease,
      and the etiology of AS, remain incompletely understood. The present study aimed
      to investigate whether exogenous IL-35 was able to attenuate the formation of
      atherosclerotic lesions in apoE-/- mice, and analyze alterations in the
      expression levels of forkhead box protein 3 (Foxp3) in peripheral blood and the
      lesions during the progression of AS. ApoE-/- mice were randomly divided into two
      groups that received either a basal diet (negative control group) or a high-fat
      diet (HFD) for 4 weeks. The HFD group was further subdivided into groups that
      received IL-35, atorvastatin or no treatment for 12 weeks. Diagnostic enzyme
      assay kits were applied for the detection of plasma lipids, and hematoxylin and
      eosin staining was used to analyze the severity of atherosclerotic lesions in
      apoE-/- mice. Immunohistochemistry and flow cytometry were performed to analyze
      the expression of Foxp3 in the plasma and atherosclerotic plaques. As compared
      with the negative control group, the plasma lipids were significantly increased,
      and the lesions were obviously formed, in the HFD groups. Furthermore, the area
      of the lesion was reduced in IL-35- and atorvastatin-treated groups, as compared
      with the AS control group. In addition, Foxp3 expression was upregulated in the
      plasma and lesions of the IL-35- and atorvastatin-treated groups, as compared
      with the AS control group. The present study demonstrated that IL-35 improved
      Treg-mediated immune suppression in atherosclerotic mice, thus suggesting that IL
      35 may be a novel therapeutic target for AS.

PMID- 27698749
TI  - Randomized, double-blind, placebo-controlled superiority trial of the Yiqigubiao
      pill for the treatment of patients with chronic obstructive pulmonary disease at
      a stable stage.
AB  - In traditional Chinese medicine (TCM), the Yiqigubiao pill is commonly used to
      enhance physical fitness. The current clinical trial was designed to evaluate the
      efficacy and safety of the Yiqigubiao pill as an adjuvant therapy for patients
      with stable chronic obstructive pulmonary disease (COPD). The current trial was a
      randomized, double-blind, placebo-controlled superiority trial. The participants
      were recruited from outpatients at the Traditional Chinese Medicine Hospital
      affiliated with Xinjiang Medical University (Urumqi, China) between February and
      September 2012. All participants were patients with stable COPD that were
      randomized to the Yiqigubiao pill (YQGB; n=84) or placebo (Pb; n=87) groups. The
      occurrences of acute exacerbation (AE) of COPD during the trial were recorded.
      Lung function value assessments, scoring of life quality and exercise endurance,
      arterial blood gas analysis and serum inflammatory cytokines level determination
      were performed prior to and throughout the study. A total of 139 participants
      completed the intervention and 132 participants completed the study. The interval
      between the initial intervention and the first AECOPD was greater in the YQGB
      group compared with the Pb group (P<0.01). The incidence rate of AECOPD was lower
      in the YQGB group than in the Pb group (P<0.01). Subsequent to the intervention
      or at the end of the study, the 6-min walking distance difference was longer in
      the YQGB group compared with the Pb group (P<0.01). The scores reflecting life
      quality decline became lower in the YQGB group (P<0.01). The serum levels of
      proinflammatory factors were downregulated to a greater extent in the YQGB group
      compared with the Pb group. Thus, the Yiqigubiao pill is an efficient and safe
      adjuvant therapy for the treatment of stable patients with COPD.

PMID- 27698750
TI  - Effects of phacoemulsification and intraocular lens implantation combined with
      ciliarotomy in the treatment of angle-closure glaucoma with cataract.
AB  - The aim of the present study was to examine the effects of phacoemulsification
      and intraocular lens implantation combined with ciliarotomy in the treatment of
      angle-closure glaucoma with cataract in the elderly. A total of 68 patients were
      consecutively selected and divided into the control group with 33 cases (48 eyes)
      and the observation group with 35 cases (53 eyes). Cataract surgery combined with
      trabeculectomy was performed on the patients in the control group and
      phacoemulsification cataract extraction combined with ciliarotomy was performed
      on the subjects in the observation group, to compare postoperative effects and
      complications. Following surgery, the visual acuity of patients in the two groups
      significantly improved, intraocular pressure decreased, and improvement of the
      observation group was more evident (P<0.05). Following surgery, the depth of
      central anterior chamber and width of chamber angle of patients in two groups was
      increased, and improvement of the observation group was significantly more
      evident (P<0.05). Additionally, the incidence of complications, including corneal
      swelling, shallow of anterior chamber, fibrinous exudate in iris, and filtering
      bleb leaking and following cataract removal, of patients in the observation group
      was significantly reduced compared to the control group (P<0.05). In summary, the
      results of the present study show that, phacoemulsification and intraocular lens
      implantation combined with ciliarotomy in the treatment of angle-closure glaucoma
      with cataract in the elderly is a safe and effective method and should be applied
      in the clinic.

PMID- 27698751
TI  - Effect of adefovir dipivoxil on T cell immune function in the treatment of
      chronic hepatitis B and hepatocirrhosis.
AB  - The aim of the present study was to investigate the T cell immune function in
      chronic hepatitis B hepatocirrhosis patients at the compensated and decompensated
      stage following treatment with adefovir dipivoxil. A total of 104 patients
      diagnosed with hepatitis B hepatocirrhosis during the period from October 2013 to
      October 2014 were enrolled in the study. Among the cases, there were 56 cases at
      compensated stage, and another 48 at decompensated stage. Adefovir dipivoxil was
      administered for antiviral therapy (10 mg/time, 1 time/day, for a total of 24
      weeks), and we compared the virus disappearance rate, liver function improvement
      and T cell immune function between the two groups before and after treatment. The
      difference between the virus disappearance rate in the two groups was not
      statistically significant (P>0.05). The decreased level of ALT decrease in the
      compensated group was significantly higher than that in the decompensated group,
      while the increased level of albumin in the compensated group was significantly
      higher as well. The differences showed statistical significance (P<0.05). After
      treatment, the level of CD4+ and CD4+/CD8+ ratio were higher than before
      treatment, while the level of CD8+ was lower after treatment than before
      treatment in the two groups. The differences all showed statistical significance
      (P<0.05). The CD4+CXCR5+ T follicular helper (TFH) cell level in the two groups
      was higher after treatment, as was interleukin-2 and interferon-gamma. The
      differences all showed statistical significance (P<0.05). As for comparison
      between groups, the difference had no statistical significance (P>0.05). Adefovir
      dipivoxil treatment can improve T cell immune function at the compensated and
      decompensated stages in chronic hepatitis B hepatocirrhosis patients. This may be
      associated with virus disappearance and liver function improvement.

PMID- 27698752
TI  - Serum biomarkers combined with uterine artery Doppler in prediction of
      preeclampsia.
AB  - First-trimester screening may be a major advantage over a second-trimester
      approach since it opens prospects for early and more efficient interventions. The
      aim of the current study was to evaluate whether the measurement of maternal
      serum inhibin A, activin A and placental growth factor (PlGF) at three to four
      months gestation with the second-trimester uterine artery pulsatility index (PI)
      are useful in predicting preeclampsia in a group of nulliparous women. All the
      patients also underwent uterine artery Doppler examination to measure the PI at
      22-24 weeks gestation. Inhibin A, activin A and PlGF were measured using an ELISA
      by an examiner who was blinded to the pregnancy outcome. Thirty-eight cases with
      preeclampsia and 100 controls were analyzed. Second-trimester uterine artery PI
      and marker levels were expressed as multiples of the median (MoM). The uterine
      artery PI was increased in pregnancies with preeclampsia compared with controls.
      In pregnancies that developed preeclampsia, the uterine artery PI was increased
      (1.61+/-0.047 vs. 1.02+/-0.049, P<0.001), as was the level of inhibin A (1.72+/
      0.023 vs. 1.03+/-0.063, P<0.001) and the level of activin A (1.68+/-0.38 vs.
      1.06+/-0.42, P<0.001) compared with the controls. In contrast, the level of PlGF
      was decreased in pregnancies that developed preeclampsia compared with the
      controls (0.69+/-0.23 vs. 1.00+/-0.26, P<0.001). A combination of activin A, PlGF
      and uterine artery PI gave an AUC of 0.915 (95% CI, 0.812-0.928; P<0.001) with a
      sensitivity of 91% at a specificity of 82%. In our study, we demonstrated that
      both serum inhibin A and activin A levels were increased, while the PlGF level
      was decreased in the early second-trimester in women who developed preeclampsia.

PMID- 27698753
TI  - Local application of low-dose insulin in improving wound healing after deep burn
      surgery.
AB  - The clinical effects of local application of low-dose insulin in improving wound
      healing after deep burn self-skin transplantation surgery were examined. Fifty
      eight patients with deep burns were selected and randomly divided into 3 groups.
      In the blank control group, normal saline was injected to the subcutaneous tissue
      of wounds; in large dose insulin group, 1.0 u long-term suspended zinc insulin
      was locally injected; and in the low-dose insulin group, 0.1 u long-term
      suspended zinc insulin was locally injected. The healing effects were compared.
      After 7 and 14 days of treatments, wound surface area in the low-dose group was
      significantly smaller than in the other groups, and differences were
      statistically significant (P<0.05); wound healing duration and infection rate for
      patients in the low-dose group were significantly lower, class A healing rate was
      significantly improved, and the differences were statistically significant
      (P<0.05). Insulin resistance index (HOMA-IR) in the low-dose group was
      significantly lower, insulin secretion index (HOMA-beta) and the insulin
      sensitivity index (HOMA-ISI) significantly increased. The expression levels of
      vascular endothelial growth factor and tumor necrosis factor-alpha in local
      tissue for the low-dose group were significantly higher than those in the other
      two groups. Differences were statistically significant (P<0.05). In conclusion,
      local application of low-dose insulin can effectively improve wound healing after
      deep burn surgeries.

PMID- 27698754
TI  - Oral paracetamol vs. oral ibuprofen in the treatment of symptomatic patent ductus
      arteriosus in premature infants: A randomized controlled trial.
AB  - The aim of the present study was to analyze the changes of plasma and urinary
      prostaglandin E2 (PGE2) levels in preterm infants with symptomatic patent ductus
      arteriosus (sPDA) treated with oral ibuprofen and acetaminophen. A total of 87
      preterm infants with sPDA admitted to the Neonatal Ward of the Affiliated Xuzhou
      Hospital of Medical College of Southeast University from October, 2012 to June,
      2015 were selected and randomly divided into the ibuprofen group (n=43, 10 mg/kg
      ibuprofen administered orally as initial dose, followed by 5 mg/kg during the
      first 24 and 48 h later) and acetaminophen group (n=44, 15 mg/kg acetaminophen
      administered orally once every 6 h for three days). The levels of plasma and
      urinary PGE2 in the two groups were estimated before and after treatment. The
      treatment of sPDA infants with ibuprofen (ibuprofen group) or acetaminophen
      (acetaminophen group) caused a significant decrease in the plasma and urinary
      PGE2 levels in comparison with plasma and urinary PGE2 levels before treatment
      (P<0.05). Furthermore, plasma and urinary PGE2 levels in the acetaminophen group
      (45.0+/-36.9 ng/l) were significantly lower than those in the ibuprofen group
      (73.5+/-44.8 ng/l, P=0.002). The arterial duct closure rate was similar between
      the acetaminophen [31 (70.5%)] and ibuprofen groups [33 (76.7%), P=0.506]. The
      incidence of oliguria was less among sPDA infants of the acetaminophen group [1
      (2.3%)] than observed among the sPDA infants of the ibuprofen group [6 (14.0%)];
      however, this difference was not statistically significant (P=0.108).
      Additionally, the incidences of fecal occult blood positive rate,
      intraventricular hemorrhage, neonatal necrotizing enterocolitis and
      bronchopulmonary dysplasia were distributed similarly in the ibuprofen and
      acetaminophen groups (P>0.05). The levels of platelet, serum creatinine and
      alanine transaminase showed no significant changes between the ibuprofen and
      acetaminophen groups (P>0.05). Following treatment with ibuprofen or
      acetaminophen, the extent of decrease of plasma and urinary PGE2 was
      significantly higher among sPDA infants with oliguria (135.0+/-38.0 ng/l) than
      that observed in sPDA infants without oliguria (52.5+/-37.0 ng/l) (P=0.01). The
      study also found a significant correlation between plasma and urinary PGE2 levels
      (r=0.648, P=0.01) and the coefficient of variation of urinary PGE2 (0.427) was
      less than that of plasma PGE2 (0.539). The clinical efficacy of oral ibuprofen
      and acetaminophen in the treatment of preterm infants with sPDA was similar with
      low adverse events, whereas acetaminophen-induced PGE2 levels were less than the
      levels observed in the ibuprofen-treated group. The incidence of oliguria was
      also lower in the acetaminophen group compared to the ibuprofen group. In
      addition, monitoring urinary PGE2 levels was more suitable because of its non
      invasiveness in the clinical setting than monitoring of plasma PGE2 in preterm
      infants with sPDA.

PMID- 27698755
TI  - LSKL peptide alleviates subarachnoid fibrosis and hydrocephalus by inhibiting
      TSP1-mediated TGF-beta1 signaling activity following subarachnoid hemorrhage in
      rats.
AB  - Hydrocephalus has been demonstrated to be an independent risk factor for poor
      outcomes in patients with subarachnoid hemorrhage (SAH). Blockage of
      cerebrospinal fluid (CSF) flow and drainage is widely considered to play a vital
      role in communicating hydrocephalus, possibly due to subarachnoid fibrosis. A
      previous study indicated that transforming growth factor-beta1 (TGF-beta1), a key
      fibrogenic factor, is significantly increased in the CSF following SAH, implying
      a pivotal role in the development of chronic hydrocephalus. To investigate
      whether LSKL peptide, a small molecular peptide and competitive antagonist for
      TGF-beta1, protects against subarachnoid fibrosis and hydrocephalus after SAH, a
      two-hemorrhage injection model of SAH was created in Sprague-Dawley rats. LSKL (1
      mg/kg) was administered intraperitoneally immediately following the first
      intravenous injection of blood in the SAH model, with repeated injections of LSKL
      every 12 h until sacrifice. Thrombospondin-1 (TSP1), TGF-beta1, p-Smad2/3,
      collagen I and pro-collagen I c-terminal propeptide levels were assessed via
      western blotting and ELISA. Lateral ventricular index, Masson staining and Morris
      water maze tests were employed to evaluate subarachnoid fibrosis, hydrocephalus
      and long-term neurological function following SAH. It was found that the LKSL
      peptide readily crossed the blood brain barrier, was protective against
      subarachnoid fibrosis, attenuated ventriculomegaly and effectively suppressed
      hydrocephalus. In addition, the results indicated that the protective effects of
      the LSKL peptide were achieved via the inhibition of TGF-beta1 activity and
      subsequent Smad2/3 signaling. Importantly, the LSKL peptide may improve long-term
      neurocognitive deficits after SAH. In conclusion, the LSKL peptide suppresses
      subarachnoid fibrosis via inhibition of TSP1-mediated TGF-beta1 activity,
      prevents the development of chronic hydrocephalus and improves long-term
      neurocognitive defects following SAH.

PMID- 27698756
TI  - Application of levator veli palatini retropositioning combined with Buccinator
      myomucosal island flap for congenital cleft palate.
AB  - Congenital cleft palate causes a serious obstacle to children with regard to
      language and eating function. The aim of the current study was to examine the
      clinical application of a type of palatoplasty that has a reduced impact on the
      maxillary growth and good function in velopharyngeal competence. A total of 37
      patients with cleft palate were treated with levator veli palatini
      retropositioning combined with Buccinator myomucosal island flap. The patients
      were successfully treated in the first phase and were followed up for 1-3 years.
      Speech intelligibility was satisfactory and no fistula occurred. In conclusion,
      the results suggested that levator veli palatini retropositioning combined with
      the Buccinator myomucosal island flap may restore normal anatomic structure and
      location of the levator veli palatini, obtain good velopharyngeal competence, and
      decrease the incidence rate thereof. Thus, levator veli palatini retropositioning
      combined with the Buccinator myomucosal island flap is a functional procedure for
      cleft palate repair.

PMID- 27698757
TI  - Role of the renal sympathetic nerves in renal sodium/potassium handling and renal
      damage in spontaneously hypertensive rats.
AB  - Renal sympathetic nerve activity has an important role in renal disease
      associated hypertension and in the modulation of fluid homeostasis. In the
      present study, changes in renal function and renal sodium/potassium handling were
      investigated in groups of 12-week-old male, spontaneously hypertensive rats with
      renal denervation (RDNX group) or sham denervation (sham group). The RDNX group
      excreted significantly more sodium than the sham group during the 2-week
      observation period (P<0.05). Following bilateral renal denervation, the
      fractional lithium excretion was elevated in the RDNX group compared with the
      sham group, but no significant effect was observed of renal denervation on the
      fractional distal reabsorption rate of sodium or the fractional excretion of
      potassium. Furthermore, the glomerular injury score and the wall-to-lumen ratio
      of the interlobular artery were significantly lower in the RDNX group than in the
      sham group (P<0.05). In conclusion, the present study indicates an involvement of
      the renal sympathetic nerves in the regulation of renal tubular sodium
      reabsorption in spontaneously hypertensive rats and in the renal damage
      associated with hypertension.

PMID- 27698758
TI  - Mucosa-reparing and microbiota-balancing therapeutic effect of Bacillus subtilis
      alleviates dextrate sulfate sodium-induced ulcerative colitis in mice.
AB  - Gut microbiota composition of patients with ulcerative colitis (UC) is markedly
      altered compared with healthy individuals. There is mounting evidence that
      probiotic therapy alleviates disease severity in animal models and patients with
      inflammatory bowel disease (IBD). Bacillus subtilisis, as a probiotic, has also
      demonstrated a protective effect in IBD. However, the therapeutic mechanism of
      its action has yet to be elucidated. In the present study, a dextrose sulfate
      sodium (DSS)-induced UC mouse model was used to investigate the role of B.
      subtilis in the restoration of gut flora and determine its effective dose.
      Mucosal damage was assessed by performing alcian blue staining, cytokine levels
      were analyzed by ELISA and microbiota composition was investigated using 454
      pyrosequencing to target hypervariable regions V3-V4 of the bacterial 16S
      ribosomal RNA gene. The results demonstrated that a higher dose B. subtilisis
      administration ameliorated DSS-induced dysbiosis and gut inflammation by
      balancing beneficial and harmful bacteria and associated anti- and pro
      inflammatory agents, thereby aiding intestinal mucosa recovery from DSS-induced
      injuries. These findings indicate that choosing the correct dose of B. subtilis
      is important for effective UC therapy. The present study also helped to elucidate
      the mechanisms of B. subtilis action and provided preclinical data for B.
      subtilis use in UC therapy.

PMID- 27698759
TI  - Delayed protective effect of telmisartan on lung ischemia/reperfusion injury in
      valve replacement operations.
AB  - The present study aimed to investigate the delayed protective effect of
      telmisartan on lung ischemic/reperfusion injury in patients undergoing heart
      valve replacement operations. In total, 180 patients diagnosed with rheumatic
      valve diseases were randomly divided into the telmisartan (T), captopril (C) and
      placebo (P) groups. In the telmisartan group, the patients were pretreated with
      telmisartan (1 mg/kg/day), at the time period 96-48 h before the operation,
      whereas in the C group, the patients were treated with captopril (1 mg/kg/day) at
      the time period 96-48 h prior to the operation control group. Each drug treatment
      group included a corresponding placebo treatment. The variables pulmonary
      vascular resistance (PVR) and A-aDO2 were measured prior to CPB and at 1, 3, 6
      and 12 h after CPB. Pulmonary neutrophil (PMN) count in the left and right atrium
      blood as well as SOD malondialdehyde (MDA), NO, angiotensin II (AngII) value in
      the left atrium blood, were measured 30 min prior to and after CPB. The PVR
      parameters of the telmisartan and captopril groups were significantly lower than
      those of the placebo group (P<0.05). The A-aDO2 values in the telmisartan and
      captopril groups were significantly lower than those in the placebo group at 1, 3
      and 6 h following CPB treatment. The difference between the right and left atrium
      blood PMN was significantly lower in the telmisartan and captopril intervention
      groups compared to that in the placebo group 30 min following CPB treatment. The
      left atrium blood SOD and NO values were significantly higher, whereas the MDA
      value was significantly lower in the telmisartan group compared to the control
      group 30 min following CPB treatment. As for AngII, there was no difference
      between the C and T groups, compared with the P group. In the two groups 30 min
      after treatment with CPB, 24 patients experienced varying degrees of cough, with
      the telmisartan group showing a significant difference (P<0.05). The
      hospitalization time was compared in the three groups of patients and it was
      found to be significantly shorter in the telmisartan group than the captopril and
      placebo groups (P<0.05). In conclusion, it was found that for the time period 96
      48 h before heart valve replacement operations telmisartan (1 mg/kg/day) delayed
      the protective effect on lung ischemia/reperfusion injury in patients with
      rheumatic valve diseases. The results of the present study indicated that the
      protective effect may be associated with the increment of endogenetic NO and the
      enhanced ability against lipid peroxidation.

PMID- 27698760
TI  - Part of plasmapheresis with plasma filtration adsorption combined with continuous
      hemodiafiltration in the treatment of severe acute liver failure.
AB  - The present study is a retrospective analysis of 11 cases with severe acute liver
      failure combined with multiple organ dysfunction syndrome (MODS) performed during
      the period June, 2012 to December, 2014. After part of plasmapheresis with plasma
      filtration adsorption combined with continuous hemodiafiltration treatment, good
      curative effects were obtained and the main clinical symptoms and biochemical
      index were significantly improved. Following treatment, 8 of the 11 patients
      survived at a survival rate of 72.7%, and 3 patients succumbed with a mortality
      of 27.3%. The results suggested that part of plasmapheresis with plasma
      filtration adsorption combined with continuous venovenous hemodiafiltration
      (CVVHDF) treatment is beneficial in the removal of metabolites and toxins.
      Additonally, it can effectively improve liver function and clinical symptoms,
      improve hepatic encephalopathy, correct the disorder of internal environment, and
      improve the prognosis of patients.

PMID- 27698761
TI  - Aminoglycoside antibiotics for NIH category II chronic bacterial prostatitis: A
      single-cohort study with one-year follow-up.
AB  - Although fluoroquinolones are first-line agents for the treatment of National
      Institutes of Health (NIH) category II chronic bacterial prostatitis (CBP),
      therapy with these agents is not always feasible due to the increasing worldwide
      resistance of causative uropathogens. New therapeutic options are urgently
      required, as drugs such as beta-lactam antibiotics distribute poorly to prostatic
      sites of infection and trimethoprim therapy is often unfeasible due to high
      resistance rates. The present study aimed to analyze the efficacy of
      aminoglycosides, administered to a cohort of 78 patients affected by
      fluoroquinolone-resistant CBP, or excluded from fluoroquinolone therapy due to
      various contraindications. Patients received netilmicin (4.5 mg/kg, once-daily,
      intramuscular), combined or not with a beta-lactam antibiotic, for 4 weeks.
      Follow-up visits were scheduled 6 and 12 months after the end of treatment. Fifty
      five out of 70 patients (78.6%) showed eradication of the causative pathogen, and
      a significant reduction of the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI)
      total score from a baseline median value of 21 to 14 at the end of therapy, and
      to 9 and 8 at 6-month and 12-month follow-up assessments, respectively. The pain,
      voiding and quality of life subdomains of the NIH-CPSI decreased accordingly. In
      15 patients showing persistence of infection, NIH-CPSI total and subdomain scores
      did not decrease at the end of therapy. Additional clinical parameters, such as
      the urinary peak flow rate, percentage voided bladder, serum prostate-specific
      antigen concentration, International Prostate Symptom Score and prostate volume
      improved significantly only in the group of patients in which the infection was
      eradicated. Therapy was well tolerated, and genetic testing for deafness
      predisposing mitochondrial mutations allowed safer administration of
      aminoglycosides. These results suggest that aminoglycosides may become a
      therapeutic alternative for the treatment of CBP. These findings should be
      further validated in a randomized-controlled setting.

PMID- 27698762
TI  - TFP5 prevents 1-methyl-4-phenyl pyridine ion-induced neurotoxicity in mouse
      cortical neurons.
AB  - The present study aimed to investigate the protective effect of a modified p5
      peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP+)-induced neurotoxicity in
      cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's
      disease (PD). MPP+ was applied to a primary culture of mouse cortical neurons to
      establish the cell model of PD. Neurons were divided into four groups: Control,
      model (MPP+), scrambled peptide (Scb) (Scb + MPP+) and TFP5 (TFP5 + MPP+) groups.
      Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively,
      for 3 h, while phosphate-buffered saline was applied to the control and model
      groups. MPP+ was then applied to all groups, with the exception of the control
      group, and neurons were cultured for an additional 24 h. Neuron viability was
      evaluated using a Cell Counting kit-8 (CCK8) assay. To explore the mechanism
      underlying the protective effects of TFP5, the expression levels of p35, p25 and
      phosphorylated myocyte enhancer factor 2 (p-MEF2D) were determined by western
      blotting. Fluorescence microscopy showed that TFP5 was able to pass through cell
      membranes and distribute around the nucleus. CCK8 assay showed that neuronal
      apoptosis was dependent on MPP+ concentration and exposure time. Cell viability
      decreased significantly in the model group compared with the control group (55+/
      7 vs. 100+/-0%; P<0.01), and increased significantly in the TFP5 group compared
      with the model group (98+/-2 vs. 55+/-5%; P<0.01) and Scb group (98+/-2 vs. 54+/
      4%; P<0.01). Scb exhibited no protective effect. Western blotting results showed
      that MPP+ induced p25 and p-MEF2D expression, TFP5 and Scb did not affect MPP+
      induced p25 expression, but TFP5 reduced MPP+-induced p-MEF2D expression. In
      summary, TFP5 protects against MPP+-induced neurotoxicity in mouse cortical
      neurons, possibly through inhibiting the MPP+-induced formation and elevated
      kinase activity of a cyclin-dependent kinase 5/p25 complex.

PMID- 27698763
TI  - Observation on therapeutic efficacy of rt-PA intravenous thrombolysis combined
      with compound anisodine injection on central retinal artery occlusion.
AB  - The aim of the present study was to observe the clinical efficacy and safety of
      recombinant tissue plasminogen activator (rt-PA) combined with compound anisodine
      in treating central retinal artery occlusion (CRAO). Forty-eight patients
      diagnosed with CRAO were randomly divided into a treatment group (24 cases) and a
      control group (24 cases). For the control group, nitroglycerin, 654-2,
      methazolamide, puerarin and compound anisodine were used for the treatment, along
      with oxygen, massage and other conventional treatments. Besides conventional
      therapy, the treatment group was also given intravenous rt-PA thrombolysis.
      Visual acuity, fundus oculi, visual field changes were taken as indicators for
      efficacy evaluation. It was found that the total effective rate of the control
      group was 70.83%, while that for the treatment group was 91.67%, and the
      comparative difference between the two groups was of statistical significance
      (p<0.05). The visual field defect of the control group after treatment was
      approximately 74.26+/-12.91%, and the visual field defect of the treatment group
      after treatment approximately 35.08+/-16.33%; thus, the comparative difference
      was statistically significant (p<0.01). The comparative difference of the
      original contents of fibrous protein in blood in the treatment group before and
      after treatment was statistically significant (p<0.01). In conclusion, the result
      show that intravenous thrombolysis with rt-PA combined with compound anisodine is
      safe and effective in treating CRAO, which can significantly improve the
      prognosis of patients.

PMID- 27698764
TI  - Protective effects of dexmedetomidine combined with flurbiprofen axetil on
      remifentanil-induced hyperalgesia: A randomized controlled trial.
AB  - High dosages of intra-operative remifentanil are associated with opioid-induced
      hyperalgesia (OIH). The aim of the present study was to investigate the effect of
      combined dexmedetomidine and flurbiprofen axetil treatment on remifentanil
      induced hyperalgesia. Patients with an American Society of Anesthesiologists
      physical status of I-II who were diagnosed with hysteromyoma and scheduled for
      laparoscopic assisted vaginal hysterectomy (LAVH) were randomly divided into
      three groups. Group hyperalgesia (Group H, n=29) received intra-operative
      remifentanil, Group hyperalgesia and dexmedetomidine (Group HD, n=28) received
      remifentanil and a continuous infusion of dexmedetomidine, and Group
      hyperalgesia, dexmedetomidine and flurbiprofen axetil (Group HDF, n=29) received
      remifentanil, flurbiprofen axetil and dexmedetomidine. Mechanical pain thresholds
      were measured during the preoperative visit and postoperatively at 1, 6 and 24-h
      time points. Visual analog scale (VAS) scores, time to analgesic requirement,
      total sufentanil consumption and side effects were assessed postoperatively.
      Mechanical pain threshold at the incision site was significantly lower in Group H
      compared with Groups HD and HDF (both P<0.05), and significantly higher in Group
      HDF than in Group HD (P<0.05). The area of secondary hyperalgesia at the incision
      site was greater in Group H than in the other two groups (both P<0.05), and
      significantly smaller in Group HDF compared with Group HD (P<0.05). VAS scores
      and total sufentanil consumption were significantly higher in Group H compared
      with the other two groups (both P<0.05), and were significantly lower in Group
      HDF compared with Group HD (P<0.05). Dexmedetomidine combined with flurbiprofen
      axetil exhibits synergetic effects in the prevention of remifentanil-induced
      hyperalgesia in patients undergoing LAVH.

PMID- 27698765
TI  - Association of genetic polymorphisms of GALNT3 and VDR with osteoporosis in
      postmenopausal women.
AB  - The correlation of genetic polymorphisms of GALNT3 and vitamin D receptor (VDR)
      with osteoporosis in postmenopausal women was investigated. A total of 1,212
      cases of postmenopausal patients diagnosed with osteoporosis (observation group)
      and 404 cases of postmenopausal women without osteoporosis (control group) were
      selected. Dual-energy X-ray absorptiometry was used for measurement of bone
      mineral density (BMD) of lumbar vertebrae L2-4, proximal femoral neck and total
      hip, and classifications were made. TaqMan genotyping technology was employed to
      examine tag single-nucleotide polymorphism (tagSNP) of GALNT3 and VDR and the
      correlation of tagSNP with bone turnover markers (BTMs) and serum calcium and
      phosphorous levels was analyzed. The multiple logistic regression analysis was
      used to screen risk factors for osteoporosis. A comparison of age and menopause
      time of the two groups, yielded no statistical significance difference (P>0.05).
      BMD and T values of the lumbar vertebrae, femoral neck and total hip in the
      observation group were significantly lower than those in the control group, and
      the differences were statistically significant (P<0.05). A comparison of the
      degree of osteoporosis, yielded statistically significant differences (P<0.05).
      The proportion of tagSNP of 5 loci in GALNT3 and 3 loci in VDR in the observation
      group was significantly higher than that in the control group, and the
      differences were of statistical significance (P<0.05). Levels of 25-OHD3, beta
      CTX, P1NP and serum calcium in the observation group were lower than those in the
      control group and the level of serum phosphorus in the observation group was
      higher than that in the control group, and all of these results were
      statistically significant (P<0.05). The result of the correlation analysis
      revealed that rs1425000 and rs757343 were negatively correlated with BTM and
      serum calcium and phosphorus levels (P<0.05). The result of the regression
      analysis revealed that 8 tagSNPs were independent risk factors for osteoporosis.
      Genetic polymorphisms of GALNT3 and VDR were closely associated with osteoporosis
      in postmenopausal women.

PMID- 27698766
TI  - Establishment of ApoE-knockout mouse model of preeclampsia and relevant
      mechanisms.
AB  - In the present study, we established an ApoE-knockout mouse model of preeclampsia
      to examine the role of vascular endothelial injury associated with abnormal lipid
      metabolism in the pathogenesis of preeclampsia. To establish the ApoE-knockout
      homozygous (ApoE-/-) and heterozygous (ApoE+/-) mouse model, mice were mated with
      the same genotype and orbital blood on day 19 of conception was collected. The
      progeny mice were assigned into 3 groups: ApoE-/, ApoE+/- and wild-type (WT)
      groups. Total cholesterol, triglyceride, low-density and high-density lipoprotein
      were measured in the serum at the end of conception. During conception, the
      systolic blood pressure of caudal artery was measured every 4 days. Using
      bicinchoninic acid protein assay, urinary protein and creatinine ratio was
      measured with a creatinine kit. We observed the pathological changes of
      glomerular filtration membrane and macroscopic/microscopic morphological changes
      of placenta by hematoxylin and eosin (H&E) staining and transmission electron
      microscope. Take fetal mouse through cesarean section on 19th day, measure the
      birth weight and placental weight of fetal mouse. Using ELISA we measured the
      expression levels of toll-like receptor 4 (TLR4) and soluble fms-like tyrosine
      kinase-1 (sFlt-1). Our results showed that the differences in serum lipid levels
      were not statistically significant (P>0.05). The mean systolic blood pressure,
      urinary protein and creatinine in ApoE-/- group were significantly higher than
      ApoE+/- group and WT group (P<0.05). Thickening and edema of glomerular
      filtration membrane, capillary thrombosis, significant edema and necrosis of
      placental villous stroma were observed in ApoE-/- group. No significant change
      was detected in the ApoE+/- or WT group. The TLR4 and sFlt-1 expression levels in
      ApoE-/- group were significantly higher than ApoE+/- and WT group (P<0.05). We
      concluded that ApoE-knockout mouse could simulate the pathologic process of
      preeclampsia, while the changes in serum lipids were not noteworthy, thus the
      pathogenesis of preeclampsia may be mediated by TLF4 and sFlt-1.

PMID- 27698767
TI  - National trends in carotid endarterectomy and stenting in Korea from 2004 to
      2013.
AB  - Stroke imposes a substantial clinical and socioeconomic burden. Carotid
      endarterectomy (CEA) or carotid artery stenting (CAS) are proven procedures in
      stroke prevention for the lesions of extracranial carotid disease. Although
      several studies have addressed national trends regarding carotid
      revascularization in Western countries, limited data is available with respect to
      the Korean population. The aim of the present study was to identify the national
      trend in carotid revascularization in Korea over the previous decade. A serial,
      cross-sectional study was conducted with the use of time trends to analyze
      patients undergoing carotid revascularization using CEA and CAS between 2004 and
      2013. Health Insurance Review and Assessment Service data was used. The present
      study endeavored to analyze trends in the number of CEA and CAS procedures for
      the treatment of extracranial carotid disease in Medicare beneficiaries. A linear
      by-linear association was performed to determine the changes of carotid
      revascularization for the aforementioned period. A total of 23,142 patients
      received carotid revascularization between 2004 and 2013. CEA was performed in
      4,012 and CAS in 19,130 patients. The rate of total carotid revascularization per
      1,000,000 Medicare beneficiaries substantially increased during the study period
      from 22 procedures in 2004 to 57 in 2013 (risk ratio (RR), 2.59; 95% confidence
      interval (CI), 1.58-4.24; P=0.001). CAS increased from 18 procedures in 2004, to
      45 in 2013 (RR, 2.50; 95% CI; 1.45-4.32; P=0.001). In addition, the number of CEA
      procedures performed per 1,000,000 Medicare beneficiaries increased from four
      procedures in 2004, to 11 in 2013 (RR, 2.75; 95% CI, 0.88-8.64; P=0.08). In
      conclusion, total carotid revascularization increased by 255% during the previous
      10 years in Korea. This increase predominantly resulted from the 249% increase of
      CAS. The number and population-based rates of carotid revascularization remained
      low, as compared with Western countries.

PMID- 27698769
TI  - MicroRNA-129-5p inhibits vascular smooth muscle cell proliferation by targeting
      Wnt5a.
AB  - Aberrant smooth muscle cells (SMCs) play important roles in the formation of
      abdominal aortic aneurysm (AAA). Although the molecular mechanism of AAA
      formation has been investigated, there is a lack of understanding concerning the
      role of microRNAs (miRNAs) in AAA, which the current study aimed to address.
      Firstly, miRNA array analysis was performed in order to compare the miRNA
      profiles in a mouse model of AAA with those in normal control mice, and
      differentially expressed miRNAs were identified. miR-129-5p was selected for
      further analysis, and was used to transfect human SMCs. The results of an MTT
      assay revealed that miR-129-5p inhibited the proliferation of SMCs, and flow
      cytometry indicated that apoptosis was induced. Bioinformatic analysis predicted
      that Wnt5a was the potential target gene of miR-129-5p, and this was verified by
      luciferase assay. In summary, miR-129-5p inhibits cellular proliferation, induces
      apoptosis and modulates the Wnt5a signaling pathway in SMCs.

PMID- 27698768
TI  - Effect of pioglitazone on neuropathic pain and spinal expression of TLR-4 and
      cytokines.
AB  - The molecular mechanisms underlying neuropathic pain have yet to be elucidated.
      The present study aimed to examine the modulation of neuroimmune activation in
      the spinal cord by the synthetic peroxisome proliferator-activated receptor gamma
      (PPAR-gamma) agonist, pioglitazone (Pio), in a rat model of neuropathic pain
      induced by chronic constriction injury (CCI). Rats were randomly assigned into
      four groups: Sham surgery with vehicle, chronic constriction injury with vehicle
      or Pio (10 mg/kg), and chronic constriction injury with Pio and a PPAR-gamma
      antagonist GW9662 (2 mg/kg). Pio or vehicle was administered 1 h prior to the
      surgery and continued daily until day 7 post-surgery. Paw pressure threshold was
      measured prior to surgery and on days 0, 1, 3 and 7 post-surgery. Microglia
      activation markers macrophage antigen complex-1, the mRNA expression levels of
      tumor necrosis factor alpha and interleukin-1beta, and the mRNA expression levels
      of toll like receptor (TLR-4) in the lumbar spinal cord were determined.
      Administration of Pio resulted in the prominent attenuation of mechanical
      hyperalgesia. In addition, Pio was able to significantly inhibit neuroimmune
      activation characterized by glial activation, the production of cytokines and
      expression levels of TLR-4. Concurrent administration of a PPAR-gamma antagonist,
      GW9662, reversed the effects of Pio. The antihyperalgesic effect of
      administration of Pio in rats receiving CCI may, in part, be attributed to the
      inhibition of neuroimmune activation associated with the sustaining of
      neuropathic pain.

PMID- 27698770
TI  - Multimodal imaging findings of SAPHO syndrome with no skin lesions: A report of
      three cases and review of the literature.
AB  - Synovitis, acne, palmoplantar pustulosis, hyperostosis and osteitis syndrome
      (SAPHO) is a rare syndrome that affects the skin, bones and joints. Diagnosis of
      SAPHO syndrome is established on clinical appearance and imaging features. The
      present case report described the imaging features of three cases of SAPHO with
      sternoclavicular joint arthritis but without skin manifestations using multiple
      imaging modalities, including computed tomography (CT), magnetic resonance
      imaging (MRI) and bone scintigraphy. The first case was a 52-year-old male who
      suffered from progressive sternoclavicular arthritis for 2 years. The second case
      was a 62-year-old female with arthritis in the larger joints for 5 years,
      particularly on the right thoracic area. The third case was a 44-year-old male
      who exhibited a slight bulge accompanied by pain in the upper anterior chest wall
      for 4 years. All of them lacked cutaneous lesions. CT demonstrated sclerosis and
      hyperostosis with subchondral erosions in the sternocostoclavicular joints. MRI
      revealed bone marrow edema that was slightly hypointense on T1-weighted imaging,
      and hyperintense on T2-weighted imaging. Typical 'bull head' signs were observed
      in bone scintigraphy images. The present case study demonstrated that SAPHO
      syndrome should be suspected in patients with multifocal osteitis or arthritis
      affecting the chest wall that lack skin manifestations. Multimodal imaging
      modalities in combination are helpful for SAPHO diagnosis.

PMID- 27698771
TI  - Identification of the protective effects of traditional medicinal plants against
      SDS-induced Drosophila gut damage.
AB  - Traditional medicinal plants are widely used as immunomodulatory medicines that
      help improve health. A total of 50 different plants used for the treatment of
      toxicity were screened for their in vivo protective effects. Flies were fed a
      standard cornmeal-yeast medium (control group) or the standard medium containing
      medicinal plant extracts (experimental groups). Assessment of the survival rate
      was performed by feeding flies with toxic compounds. Gut epithelial cells were
      analyzed for cell proliferation and death by green fluorescent protein antibodies
      and 7-aminoactinomycin D staining under the microscope. The expression of
      antimicrobial peptides (AMPs) was evaluated by the quantitative polymerase chain
      reaction and the results revealed that after feeding the flies with toxic
      compounds, aqueous extracts from Codonopsis pilosula (Franch.) Nannf (C.
      pilosula), Saussurea lappa (Decne.) C.B.Clarke (S. lappa), Imperata cylindrica
      Beauv.var.major (Nees) C.E. Hubb. (I. cylindrical var. major) and Melia toosendan
      Sied. Et Zucc. (M.toosendan) increased the fly survival rate, reduced epithelial
      cell death and improved gut morphology. In addition, C. pilosula extracts induced
      the antimicrobial peptide levels (Dpt and Mtk) following treatment with sodium
      dodecyl sulfate (SDS). However, these extracts were not observed to increase SDS
      induced cell proliferation in vivo. These results indicate that there are strong
      protective effects in extracts of C. pilosula, S. lappa, I. cylindrical var.
      major and M. toosendan on Drosophila intestinal cells among 50 medicinal plants.

PMID- 27698772
TI  - Effect of Polygonatum odoratum extract on human breast cancer MDA-MB-231 cell
      proliferation and apoptosis.
AB  - Traditional Chinese medicine (TCM) is important in the provision of anti-tumor
      drugs. Recently, studies have shown that certain types of TCM agents are able to
      control the growth of tumors, enhance the body's immune function and enhance the
      therapeutic effect of chemotherapeutic drugs. In women, breast carcinoma is the
      most common tumor type and the second most common cause of death from cancer.
      Polygonatum odoratum (P. odoratum) is commonly used in TCM. The aim of the
      present study was to investigate the effects of P. odoratum extract on the
      proliferation and apoptosis of MDA-MB-231 breast cancer cells. Cell proliferation
      was assessed using MTT and colony formation assays. In addition, propidium iodide
      (PI)/Annexin V-FITC staining was used to investigate the apoptosis of MDA-MB-231
      cells following treatment with P. odoratum extract. The protein expression levels
      of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were also
      detected using western blot analysis, while a JC-1 staining assay was used to
      assess the mitochondrial membrane potential (DeltaPsim). The results of the MTT
      assay showed that the proliferation and colony formation of MDA-MB-231 cells were
      inhibited following treatment with the extract. Furthermore, the PI/Annexin-V
      staining showed that the apoptosis of MDA-MB-231 cells was enhanced by the
      extract, in a concentration-dependent manner. The extract also lowered the
      DeltaPsim of MDA-MB-231 cells, upregulated the expression of Bax and inhibited
      the expression of Bcl-2. In conclusion, these results showed that the P. odoratum
      extract inhibited the proliferation and induced apoptosis of breast cancer MDA-MB
      231 cells.

PMID- 27698773
TI  - Neural stem cell transplantation combined with erythropoietin for the treatment
      of spinal cord injury in rats.
AB  - Spinal cord injury (SCI) comprises nerve and motor function disorders that may be
      caused by a variety of damaging factors and is challenging to treat. The aim of
      the present study was to investigate the regenerative effects of neural stem cell
      (NSC) transplantation combined with intraperitoneal injection of erythropoietin
      (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult
      Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The
      rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO
      groups (n=10 per group). Morphological alterations associated with axonal
      regeneration were detected using neurofilament (NF)-200 immunohistochemistry and
      immunofluorescence staining after 8 weeks. Basso, Beattie and Bresnahan (BBB)
      scoring was used to evaluate the recovery of hindlimb function. A total of 5 rats
      died following surgery, including 2 control rats and 1 rat each in the EPO, NSC
      and NSC + EPO groups. NSCs labeled with bromodeoxyuridine were observed to have
      survived and migrated in the spinal cord tissue after 8 weeks. Significant
      histomorphological differences were observed in the NSC and NSC + EPO groups
      compared with the EPO and control groups. Furthermore, the rats of the NSC + EPO
      group exhibited significantly enhanced axonal regeneration in the SCI area
      compared with the NSC group rats. The rats of the NSC and NSC + EPO groups
      exhibited significantly improved BBB scores compared with the EPO and control
      group rats at 7 days after treatment (P<0.05). In addition, the BBB scores of the
      NSC + EPO group were significantly improved compared with those of the three
      other groups at 7 days after surgery (P<0.05). Therefore, the results of the
      present study suggest that NSC transplantation combined with intraperitoneal
      injection of EPO may benefit the survival and regeneration of injured axons, and
      accelerate the repair of injured spinal cord tissue, thus facilitating the
      functional recovery of hindlimb locomotor function in rats.

PMID- 27698775
TI  - Astragaloside IV ameliorates necrotizing enterocolitis by attenuating oxidative
      stress and suppressing inflammation via the vitamin D3-upregulated protein 1/NF
      kappaB signaling pathway.
AB  - Astragaloside IV (AS-IV) is a flavonoid from the plant Astragalus membranaceus
      (Fisch) Bge that has a wide range of therapeutic effects. The aim of the present
      study was to examine the effect of AS-IV on rats with necrotizing enterocolitis
      (NEC) under oxidative stress and inflammation. Newborn Sprague-Dawley rats were
      induced with NEC by asphyxia and hypothermia applied on 3 consecutive days. The
      rats were orally administered AS-IV at 25, 50 and 75 mg/kg for 4 days. The
      results revealed that AS-IV administration prevented NEC-induced decrease in the
      concentration of malondialdehyde and myeloperoxidase, and increase in the
      activity of glutathione (GSH) and superoxide dismutase in murine models. AS-IV
      also inhibited NEC-induced elevation in the levels of interleukin (IL)-6, IL
      1beta, tumor necrosis factor-alpha and nuclear factor (NF)-kappaB. The effects of
      AS-IV were achieved under inflammation and oxidative stress. Western blotting
      demonstrated that AS-IV substantially inhibited the phosphorylated (p)
      IkappaBalpha, NF-kappaBp65, p-NF-kappaBp65 protein levels and increased vitamin
      D3 upregulated protein 1 (VDUP1) and IkappaBalpha protein levels. These data
      indicate that AS-IV may be effective in the protection of NEC-induced ileum
      degeneration by inhibiting the levels of inflammatory markers and oxidative
      stress via the regulation of the VDUP1/NF-kappaB signaling pathway.

PMID- 27698774
TI  - Long-term health effects of persistent exposure to low-dose lr192 gamma-rays.
AB  - The aim of the present study was to investigate the effect of persistent low-dose
      iridium-192 (Ir192) exposure on immunological function, chromosome aberration and
      the telomerase activity of bone marrow mononuclear cells (BMNCs), in order to
      increase clinical knowledge of the late effects of persistent low-dose Ir192
      gamma-ray exposure. Patients (n=54) accidentally exposed to persistent low-dose
      Ir192 were included in this 10-year follow-up study. Clinical symptoms,
      peripheral blood, bone marrow, cellular and humoral immune status, chromosome
      aberrations and the telomerase activity of BMNCs were analyzed in this study.
      Exposure to low-dose Ir192 resulted in different degrees of clinical symptoms and
      significantly lowered complement C3 and C4 levels, CD3+, CD4+ and CD8+ T cell
      levels, the lymphocyte transformation rate and the percentage of natural killer
      (NK) cells. It also led to increases in peripheral blood and bone marrow
      abnormality rates, chromosome aberration rate and BMNC telomerase activity.
      Exposure to persistent low-dose Ir192 radiation resulted in different degrees of
      immune dysfunction, and abnormalities of blood cells and bone marrow, which
      recovered within 1-3 years. Chromosome aberrations were observed to take 5-10
      years to recover. However, it would take >10 years for the telomerase activity of
      BMNCs to be reduced to normal levels. A prolonged follow-up time is required in
      order to monitor clonal proliferative diseases such as leukemia.

PMID- 27698776
TI  - Anticancer effect of cucurbitacin B on MKN-45 cells via inhibition of the
      JAK2/STAT3 signaling pathway.
AB  - The aim of the present study was to investigate the effect of cucurbitacin B on
      MKN-45 gastric carcinoma cells. Cell proliferation was determined using a cell
      counting kit-8 assay, and commercial cell cycle and apoptosis analysis kits were
      used to determine the cell cycle by flow cytometry. The mRNA expression of genes
      which mediate cell cycle checkpoints and apoptosis was detected using reverse
      transcription-quantitative polymerase chain reaction, and a terminal
      deoxynucleotidyl transferase dUTP nick end labeling assay was used to determine
      apoptosis rate. Western blot analysis was used to detect the protein expression
      levels of JAK2/STAT3 signaling pathway-associated proteins. The presented data
      show that cucurbitacin B significantly inhibited the proliferation of MKN-45
      cells in a dose- and time-dependent manner. In accordance with these findings,
      cucurbitacin B blocked the progression of the cell cycle from G0/G1 to S phase,
      which was confirmed by the mRNA expression analysis. Cucurbitacin B treatment
      significantly suppressed the expression of cyclin D1, cyclin E, cyclin-dependent
      kinase 4 (CDK4) and CDK2, while increasing the expression of p27. Cucurbitacin B
      also promoted cell apoptosis, as was determined by TUNEL assay and evaluation of
      mRNA expression. Further experiments suggested that the beneficial effect of
      cucurbitacin B on blocking the proliferation and inducing the apoptosis of MKN-45
      cells may have been associated with suppression of the JAK2/STAT3 signaling
      pathway. Thus, the present results indicate that cucurbitacin B suppresses
      proliferation and promoted apoptosis of MKN-45 cells, which may be mediated by
      inhibition of the JAK2/STAT3 signaling pathway. Cucurbitacin B therefore may
      warrant further investigation as a feasible therapy for gastric carcinoma.

PMID- 27698777
TI  - Expression and regulation of the ery operon of Brucella melitensis in human
      trophoblast cells.
AB  - Brucellosis is primarily a disease of domestic animals in which the bacteria
      localizes to fetal tissues such as embryonic trophoblast cells and fluids
      containing erythritol, which stimulates Brucella spp. growth. The utilization of
      erythritol is a characteristic of the genus Brucella. The ery operon contains
      four genes (eryA, eryB, eryC and eryD) for the utilization of erythritol, and
      plays a major role in the survival and multiplication of Brucella spp. The
      objective of the present study was to conduct a preliminary characterization of
      differential genes expression of the ery operon at several time points after
      Brucella infected embryonic trophoblast cells (HPT-8 cells). The result showed
      that the ery operon expression was higher in HPT-8 cells compared with the
      medium. The relative expression of eryA, eryB and eryC peaked at 2 h post
      infection in HPT-8 cells, and eryD expression peaked at 3 h post-infection. The
      expression of eryA, eryB and eryC may be inhibited by increased eryD expression.
      However, the expression of the ery operon was stable in the presence of
      erythritol in cells. 2308Deltaery and 027Deltaery mutants of the ery operon were
      successfully constructed by homologous recombination, which were attenuated in
      RAW 264.7 murine macrophages. The characterization of the ery operon genes and
      their expression profiles in response to Brucella infection further contributes
      to our understanding of the molecular mechanisms of infection and the
      pathogenesis of brucellosis.

PMID- 27698778
TI  - Scrub typhus associated with hemophagocytic lymphohistiocytosis: A report of six
      pediatric patients.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune disorder
      that may be inherited or secondary to infection, malignancy or rheumatological
      disease. The aim of the present study was to highlight the clinical features of
      scrub typhus-associated HLH in children. A retrospective study was performed on 6
      pediatric patients with scrub typhus-associated HLH. For each patient, medical
      records were reviewed and analyzed, and demographic, clinical and laboratory data
      and outcomes were collected. The duration of fever prior to admission ranged
      between 4 and 12 days. All patients exhibited persistent or intermittent fever,
      eschar, hepatosplenomegaly and lymphadenopathy at the time of diagnosis. Five
      patients experienced acute respiratory distress syndrome and disseminated
      intravascular coagulation (DIC) during hospitalization. Thrombocytopenia was
      detected in all patients with cytopenia involving two or three cell types,
      simultaneously. Coagulopathy with prolonged prothrombin time and/or activated
      partial thromboplastin time were noted in all patients. Markedly elevated serum
      ferritin levels (>1,500 ug/ml) were identified in all patients. Elevated lactate
      dehydrogenase (>1,000 U/l) was detected in 4 (66.7%) patients and elevated
      alanine aminotransferase was exhibited by 5 (83/3%) patients. Lung infiltrates
      and consolidation were the most common imaging findings. Only 1 patient
      succumbed, with DIC and multi-organ failure. Of the survivors, 1 patient was lost
      to follow-up, and the remaining patients are in remission with excellent general
      health, to date. In conclusion, HLH should be considered in severe pediatric
      cases of scrub typhus. Upon the early recognition of this syndrome, prompt and
      supportive treatment in the pediatric intensive care unit are vital.

PMID- 27698779
TI  - Tanshinone IIA pretreatment attenuates ischemia/reperfusion-induced renal injury.
AB  - Tanshinone IIA is a chemical compound extracted from the root of traditional
      Chinese herb Salvia miltiorrhiza Bunge. Tanshinone IIA has been suggested to
      possess anti-inflammatory activity and antioxidizing capability. Recently,
      accumulating results have indicated the antitumor activity of tanshinone IIA;
      thus, it has attracted increasing attention. In addition, tanshinone IIA has been
      indicated to attenuate ischemia/reperfusion induced renal injury (I/RIRI);
      however, little is known regarding the underlying mechanisms involved in this
      process. In the present study an I/RIRI rat model was used to analyze the effects
      of tanshinone IIA on myeloperoxidase (MPO), TNF-alpha and IL-6 activities using
      ELISA kits. Furthermore, macrophage migration inhibitory factor (MIF), cleaved
      caspase-3, B-cell lymphoma 2 (Bcl-2) and p38 mitogen-activated protein kinase
      (MAPK) protein expression levels were evaluated using western blot analysis. The
      results indicated that tanshinone IIA protected renal function in I/RIRI rats.
      ELISA demonstrated that tanshinone IIA significantly reduced MIF, TNF-alpha and
      IL-6 activities in I/RIRI rats. Western blot analysis showed that tanshinone IIA
      significantly suppressed MIF, cleaved caspase-3 and p38 MAPK protein expression
      levels in I/RIRI rats. The present results suggest that tanshinone IIA
      pretreatment attenuates I/RIRI via the downregulation of MPO expression,
      inflammation, MIF, cleaved caspase-3 and p38 MAPK.

PMID- 27698780
TI  - miR-448 downregulates MPPED2 to promote cancer proliferation and inhibit
      apoptosis in oral squamous cell carcinoma.
AB  - The incidence of oral squamous cell carcinoma (OSCC) is continuously increasing
      while its survival rate has not notably improved. There is a pressing need for
      improved understanding of the genetic regulation of OSCC tumorigenesis and
      progression. In this study, the function of miR-448 in the regulation of OSCC
      growth and its putative target were thoroughly analyzed in vitro. The expression
      of miR-448 was detected in human OSCC specimens and OSCC cell lines (Cal-27 and
      Scc-9) by reverse transcription-quantitative polymerase chain reaction. The
      function of miR-448 was investigated in Cal-27 cells transfected with miR-448
      inhibitor, and its putative target determined using a luciferase reporter assay.
      MTT and wound healing assays and flow cytometry were used to evaluate the effects
      of miR-448 on OSCC proliferation, metastasis and apoptosis. The level of miR-448
      was significantly elevated in human OSCC tissues and the Cal-27 cell line.
      Suppression of miR-448 expression attenuated cell proliferation and migration,
      and induced apoptosis of Cal-27 cells. Furthermore, miR-448 bound with the 3'
      untranslated region of metallophosphoesterase domain containing 2 (MPPED2) mRNA,
      thereby reducing the MPPED2 protein level. Thus, it appears that miR-448 acts as
      a tumor inducer, causing OSCC growth by inhibiting the expression of its target
      MPPED2. These results demonstrate that miR-448 plays a critical role in OSCC
      tumorigenesis, and is a potential therapeutic target.

PMID- 27698781
TI  - Expression and location of HSP60 and HSP10 in the heart tissue of heat-stressed
      rats.
AB  - The present study aimed to analyze the expression levels and localizations of
      heat shock protein (HSP) 60 and HSP10 in the heart tissue of rats subjected to
      heat stress (42 degrees C) for 0, 20, 80 and 100 min. Histopathological injuries
      and increased serum activities of serum lactate dehydrogenase and creatine kinase
      isoenzyme MB were detected in the heated rat myocardial cells. These results
      suggested that heat stress-induced acute degeneration may be sufficient to cause
      sudden death in animals by disrupting the function and permeability of the
      myocardial cell membrane. In addition, the expression levels of HSP60 were
      significantly increased following 20 min heat stress, whereas the expression
      levels of its cofactor HSP10 were not. Furthermore, the location of HSP60, but
      not of HSP10, was significantly altered during periods of heat stress. These
      results suggested that HSP60 in myocardial tissue may be more susceptive to the
      effects of heat stress as compared with HSP10, and that HSP10 is constitutively
      expressed in the heart of rats. The expression levels and localizations of HSP60
      and HSP10 at the different time points of heat stress were not similar, which
      suggested that HSP60 and HSP10 may not form a complex in the heart tissue of heat
      stressed rats.

PMID- 27698782
TI  - Clinicopathological characteristics of thyroid cancer misdiagnosed by fine needle
      aspiration.
AB  - Fine-needle aspiration (FNA) is commonly used as a preoperative assessment to
      diagnose thyroid cancer. However, misdiagnosis of malignancy by FNA is not rare,
      even if image examination suggests the possibility of thyroid cancer. In the
      present study, the clinicopathological factors of patients whose preoperative FNA
      examination had not led to a diagnosis of thyroid cancer were examined. In total,
      125 patients with thyroid cancer who underwent FNA and surgery (total
      thyroidectomy, subtotal thyroidectomy or hemithyroidectomy) at the Department of
      Surgery, Surgical Oncology and Science of the Sapporo Medical University Hospital
      between 2006 and 2013 were retrospectively analyzed. The patients were divided
      into two groups: Group A, malignancy determined by FNA, and group B, no
      malignancy. The groups were then compared by gender, age, tumor size, stage,
      tumor stage, lymph node metastasis, histology, surgical procedure methods,
      presence or absence of calcification and thyroglobulin levels. The mean age of
      the patients in group A (5 males and 59 females) was 53.0 years. The mean age in
      group B (11 males and 49 females) was 54.2 years. The mean tumor size in both
      groups was 1.6 cm. The mean thyroglobulin levels were 82.7 ng/ml in Group A and
      525.5 ng/ml in group B. There were also significant differences between the
      groups for tumor stage (P=0.046), histological type (P=0.024) and thyroglobulin
      levels (P=0.035). The results of the present study suggested that it may be
      difficult to diagnose thyroid cancer by FNA in cases with non-papillary carcinoma
      and higher thyroglobulin levels.

PMID- 27698783
TI  - Increased receptor activator of nuclear factor kappabeta ligand/osteoprotegerin
      ratio exacerbates cartilage destruction in osteoarthritis in vitro.
AB  - Osteoarthritis (OA) is a degenerative joint disease characterized by progressive
      cartilage destruction, matrix degradation and bony changes. Subchondral bone
      alterations in osteoarthritis are associated with cartilage destruction. It has
      previously been demonstrated that osteoprotegerin (OPG) and receptor activator of
      nuclear factor kappabeta ligand (RANKL) mediate this process. The RANKL/OPG ratio
      is altered in OA chondrocytes compared with normal chondrocytes. In the
      pathogenesis of OA, abnormal expression levels of matrix metalloproteinase-13
      (MMP-13) are secreted by chondrocytes has a vital role in the progression of
      cartilage erosion. In the present study, the effect of various RANKL/OPG ratios
      on MMP-13 expression levels was investigated in interleukin-1beta-stimulated
      SW1353 human chondrosarcoma cells. Cell viability was assessed by MTT assay and
      MMP-13 mRNA and protein expression levels were analyzed by quantitative reverse
      transcription-quantitative polymerase chain reaction, ELISA and western blot
      analyses, respectively. The results demonstrated that an increase in MMP-13 mRNA
      and protein expression levels was observed with increasing RANKL/OPG ratio. These
      findings suggest that this mechanism may be used as a novel therapeutic strategy
      against OA.

PMID- 27698784
TI  - OMP31 of Brucella melitensis 16M impairs the apoptosis of macrophages triggered
      by TNF-alpha.
AB  - Outer membrane proteins (OMPs) of microorganisms play important roles in directly
      interacting with host cells. Brucella species inhibit the apoptosis of host cells
      to benefit their own intracellular survival and replication. However, the
      association between OMP31 of Brucella and host cell apoptosis, and the underlying
      mechanism are unclear. In this study, an OMP31 gene deletion mutant based on B.
      melitensis 16M was constructed. Following the infection of RAW264.7 cells with B.
      melitensis 16M or the mutant strain, colony formation, apoptosis, tumor necrosis
      factor (TNF)-alpha levels and the levels of key downstream factors of the
      apoptosis pathways triggered by TNF-alpha, namely caspase-3, -8 and -9,
      cytochrome c, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were
      detected. The mutant strain was shown to have the same phenotype as the parent
      strain using traditional microbiological tests. However, the mutant strain had
      impaired intracellular survival, with higher levels of apoptosis and TNF-alpha
      expression in infected RAW164.7 macrophages than the parent strain. The
      downstream factors of apoptosis triggered by TNF-alpha, including increased
      caspase-8, -3 and -9, cytochrome c and Bax, and decreased Bcl-2, indicated that
      the classical and mitochondrial cell death pathways were involved. It may be
      concluded that OMP31 from Brucella inhibited apoptosis and benefitted the
      intracellular survival of this microorganism. Furthermore, TNF-alpha may have
      served as a switch triggering classical death and mitochondrial cell death
      pathways.

PMID- 27698785
TI  - Anti-inflammatory activity of liposomes of Asparagus racemosus root extracts
      prepared by various methods.
AB  - Asparagus racemosus root extracts (AR) have been reported to possess a variety of
      pharmacological properties. The aim of the present study was to develop liposomes
      of AR and to assess their physicochemical characteristics and anti-inflammatory
      activity in the monocytic leukemia cell line THP-1. Liposomes containing various
      ratios of AR to lipid and a phosphatidylcholine to cholesterol molar ratio of 7:3
      were prepared by thin-film hydration (TF), reverse-phase evaporation (REV) and
      polyol dilution (PD). The results showed that AR liposomes prepared by TF had a
      multilamellar structure and a large size, whereas those prepared by REV and PD
      were oligolamellar in structure, and of a smaller size. The particle sizes and
      zeta potentials of the liposomes ranged from 196.5 to 456.6 nm and from -4.34 to 
      18.94 mV, respectively. The AR to lipid ratio was shown to have no significant
      influence on particle size, while the zeta potential generally increased with
      increasing AR to lipid ratio. The highest entrapment efficiency values were
      detected in liposomes with an AR to lipid ratio of 1:5, and for liposomes
      prepared by TF, REV and PD methods, the entrapment efficiencies were 55.71+/
      2.04, 56.21+/-3.59 and 67.68+/-1.37%, respectively. AR was found to exert no
      toxicity on THP-1 cells. The maximum anti-inflammatory activities of AR and AR
      liposomes, evaluated in terms of the percentage inhibition of tumor necrosis
      factor-alpha in THP-1 cells, were ~52% at a concentration of 1 ug/ml. It can be
      concluded from the present study that AR liposomes have the potential to be used
      a formulation for topical and/or transdermal drug delivery to provide anti
      inflammatory activity.

PMID- 27698786
TI  - Involvement of macrophage migration inhibitory factor in cancer and novel
      therapeutic targets.
AB  - Macrophage migration inhibitory factor (MIF) was originally identified in 1966 by
      Bloom and Bennett as a pro-inflammatory cytokine involved in the inhibition of
      macrophage motility. Since then, studies have investigated the functional
      contribution of this pro-inflammatory cytokine in several immune diseases,
      including rheumatoid arthritis and lupus erythematous. Recently, MIF has been
      reported to be involved in a variety of neoplastic diseases. The present review
      discusses previous cancer research studies that have investigated the involvement
      of MIF in carcinogenesis, disease prognosis, tumor cell proliferation and
      invasion, and tumor-induced angiogenesis. Finally, potential therapeutic
      approaches based on the use of MIF antagonists and neutralizing antibodies are
      examined. The review concludes that MIF could be a good prognostic biomarker in
      several types of cancer, but also that the inhibition of MIF could represent a
      novel therapy against cancer.

PMID- 27698788
TI  - Why man's best friend, the dog, could also benefit from an anti-HER-2 vaccine.
AB  - Human epidermal growth factor receptor-2 (HER-2) is a well-established target for
      anticancer anticancerprecision medicine in humans. A HER-2 homologue with 92%
      amino acid identity has been described in canine mammary tumors, which whichis
      termed here as 'dog epidermal growth factor receptor-2 (DER-2)', with similar
      biological implications as those in human breast cancer. Both antigens can
      principally be immunologically targeted by anti-HER-2 antibodies, such as
      trastuzumab; however, the in vivo application applicationof humanized antibodies
      to other species would lead to specific hypersensitivity reactions. Therefore,
      HER-2 mimotope vaccines that actively induce autologous trastuzumab-like
      immunoglobulins represent a novel and economic treatment option to overcome
      species-specific limitations. Thus, the present review proposes the
      implementation of clinical trials with HER-2 vaccines in canine cancer model
      modelpatients with spontaneous DER-2 positive mammary gland carcinomas in order
      to assess their safety and efficacy. This approach would not only pave the way
      into the veterinary oncology market, but would also similarly generate robust
      data for human trials and facilitate the testing of novel combinatorial
      treatments.

PMID- 27698787
TI  - Cancer stem cells as a potential therapeutic target in thyroid carcinoma.
AB  - A number of studies have indicated that tumor growth and proliferation is
      dependent on a small subset of cells, defined as cancer stem cells (CSCs). CSCs
      have the capability to self-renew, and are involved with cancer propagation,
      relapse and metastatic dissemination. CSCs have been isolated from numerous
      tissues, including normal and cancerous thyroid tissue. A regulatory network of
      signaling pathways and microRNAs (miRNAs) control the properties of CSCs.
      Differentiated thyroid carcinoma is the most common type of endocrine cancer,
      with an increasing incidence. Anaplastic thyroid carcinoma is the most rare type
      of endocrine cancer; however, it also exhibits the highest mortality rate among
      thyroid malignancies, with an extremely short survival time. Thyroid CSCs are
      invasive and highly resistant to conventional therapies, including radiotherapy
      and chemotherapy, which results in disease relapse even when the primary lesion
      has been eradicated. Therefore, targeting thyroid CSCs may represent an effective
      treatment strategy against aggressive neoplasms, including recurrent and
      radioresistant tumors. The present review summarizes the current literature
      regarding thyroid CSCs and discusses therapeutic strategies that target these
      cells, with a focus on the function of self-renewal pathways and miRNAs.
      Elucidation of the mechanisms that regulate CSC growth and survival may improve
      novel therapeutic approaches for treatment-resistant thyroid cancers.

PMID- 27698789
TI  - Role of Yes-associated protein in cancer: An update.
AB  - Yes-associated protein (YAP) is an oncoprotein located in the cytoplasm in an
      inactive form, and when activated, it translocates to the nucleus and activates
      the transcription of genes responsible for cell division and apoptosis. YAP is
      one of the downstream regulatory proteins in the Hippo signaling pathway, which
      is important in cell proliferation and regeneration. Due to its great importance,
      YAP is regulated very strictly by different regulatory systems. The present
      review will focus on the canonical pathways of YAP, and will provide details on
      the most recent findings regarding its regulation and role in tumorigenesis,
      specifically in prostate tumor progression.

PMID- 27698790
TI  - Glioblastoma multiforme: Effect of hypoxia and hypoxia inducible factors on
      therapeutic approaches.
AB  - Central nervous system-based cancers have a much higher mortality rate with the
      2016 estimates at 6.4 for incidence and 4.3 for deaths per 100,000 individuals.
      Grade IV astrocytomas, known as glioblastomas are highly aggressive and show a
      high proliferation index, diffused infiltration, angiogenesis, microvascular
      proliferation and pleomorphic vessels, resistance to apoptosis, and
      pseudopalisading necrosis. Extensive hypoxic regions in glioblastomas contribute
      to the highly malignant phenotype of these tumors. Hypoxic regions of
      glioblastoma exacerbate the prognosis and clinical outcomes of the patients as
      hypoxic tumor cells are resistant to chemo- and radiation therapy and are also
      protected by the malfunctional vasculature that developed due to hypoxia.
      Predominantly, hypoxia-inducible factor-1alpha, vascular endothelial growth
      factor (VEGF)/VEGF receptor, transforming growth factor-beta, epidermal growth
      factor receptor and PI3 kinase/Akt signaling systems are involved in tumor
      progression and growth. Glioblastomas are predominantly glycolytic and hypoxia
      induced factors are useful in the metabolic reprogramming of these tumors.
      Abnormal vessel formation is crucial in generating pseudopalisading necrosis
      regions that protect cancer stem cells residing in that region from therapeutic
      agents and this facilitates the cancer stem cell niche to expand and contribute
      to cell proliferation and tumor growth. Therapeutic approaches that target
      hypoxia-induced factors, such as use of the monoclonal antibody against VEGF,
      bevacizumab, have been useful only in stabilizing the disease but failed to
      increase overall survival. Hypoxia-activated TH-302, a nitroimidazole prodrug of
      cytotoxin bromo-isophosphoramide mustard, appears to be more attractive due to
      its better beneficial effects in glioblastoma patients. A better understanding of
      the hypoxia-mediated protection of glioblastoma cells is required for developing
      more effective therapeutics.

PMID- 27698791
TI  - MicroRNAs and PIWI-interacting RNAs in oncology.
AB  - RNA molecules that are unable to translate into proteins are classified as non
      coding RNA. Non-coding RNA (ncRNA) genes include highly abundant and functionally
      important RNAs such as transfer RNAs, microRNAs (miRNAs), siRNAs, snRNAs, exRNAs
      and piRNAs. The number of ncRNAs encoded within the human genome is unknown;
      however, recent transcriptomic and bioinformatic studies suggest the existence of
      thousands of ncRNAs. Furthermore, small ncRNAs, including miRNAs and PIWI
      interacting RNAs (piRNAs), play an imperative role in the regulation of gene
      expression of numerous biological and pathological processes. Investigation into
      the expression and function of small RNA in cancer cells has contributed to
      gaining a greater understanding of the roles of small RNAs in carcinogenesis. The
      present review is aimed primarily to discuss the importance of the expression and
      functions of these small RNAs in carcinogenesis. These studies may provide useful
      information for future therapies in cancer.

PMID- 27698792
TI  - Expression of microRNA-181 determines response to treatment with azacitidine and
      predicts survival in elderly patients with acute myeloid leukaemia.
AB  - MicroRNAs (miRs) are small non-coding RNAs that play important roles in cell
      differentiation and survival. Abnormal expression of miRs has been demonstrated
      in numerous types of cancer, including acute myeloid leukaemia (AML). The aim of
      the present study was to evaluate miR-181 expression at diagnosis and following
      the completion of chemotherapy in AML patients, with regard to clinical response
      and outcome, particularly in patients treated with azacitidine. miR-181
      expression was analysed using reverse transcription-quantitative polymerase chain
      reaction in 95 bone marrow specimens from newly diagnosed AML patients and in 20
      healthy subjects for comparison. The results revealed upregulated miR-181
      expression in the total cohort of AML patients, which was correlated with longer
      survival. However, in a subset of older AML patients treated with azacitidine,
      low miR-181 expression at diagnosis was a predictor for complete remission and
      prolonged survival. The findings indicated that miR-181 has an important role in
      AML and determines response to azacitidine treatment in older AML patients.

PMID- 27698793
TI  - miR-186 suppressed CYLD expression and promoted cell proliferation in human
      melanoma.
AB  - Previous studies have shown that microRNA-186 (miR-186) is overexpressed in
      various human cancers and is associated with the regulation of the carcinogenic
      processes. However, the underlying mechanisms of this microRNA in melanoma remain
      largely unknown. In the present study, the overexpression of miR-186 was
      identified in melanoma tissues and melanoma cells compared to the expression of
      miR-186 in the matched tumor adjacent tissues and normal human epidermal
      melanocytes. Overexpression of miR-186 promoted the proliferation and anchorage
      independent growth of melanoma cells, whereas inhibition of miR-186 reduced this
      effect. Bioinformatics analysis also revealed cylindromatosis (CYLD), a putative
      tumor suppressor, to be a potential target of miR-186. Luciferase reporter assays
      showed that miR-186 directly targeted the 3'-untranslated regions of CYLD
      messenger RNA. Additional experiments showed that overexpression of miR-186
      promoted the proliferation of melanoma cells, which was consistent with the
      inhibitory effects induced by knockdown of CYLD. In summary, the present study
      indicated that miRNA-186 plays a crucial role in melanoma growth and its
      oncogenic effect is mediated chiefly through the direct suppression of CYLD
      expression.

PMID- 27698794
TI  - Two novel susceptibility loci for non-small cell lung cancer map to low-density
      lipoprotein receptor-related protein 5.
AB  - This study investigated the effect of single-nucleotide polymorphisms (SNPs) of
      low-density lipoprotein receptor-related protein 5 (LRP5) on the risk of
      developing non-small cell lung cancer (NSCLC). A total of 500 NSCLC patients and
      500 healthy controls were recruited for genotyping of 11 SNPs of LRP5. The
      association between genotype and NSCLC risk was evaluated by computing the odds
      ratio (OR) and 95% confidence interval (CI) from multivariate unconditional
      logistic regression analyses. Eleven Tag SNPs were detected. The frequency of the
      LRP5 rs3736228 T allele (18.9% in male NSCLC cases and 23.9% in male controls)
      was statistically different between male NSCLCs and male controls (P=0.03), and
      the T allele was associated with a lower risk of NSCLC (OR=0.74; 95% CI, 0.56
      0.67), whereas the C/C homozygous genotype and the LRP5 rs64843 T/T genotype were
      associated with an increased risk of NSCLC and squamous cell carcinoma (SCC),
      respectively (OR=1.43 and 1.77, respectively). Using Haploview software, the
      frequency of the haplotypes of rs312009/rs3120015/rs3120014 CCC was was
      significantly higher in female SCC cases compared with female controls (0.064 vs.
      0.009, P=0.04). LRP5 rs3736228 and rs64843 SNPs were significantly associated
      with an increased risk of NSCLC and SCC, respectively. Further studies are
      required to investigate the functional changes in LRP5 expression and activity in
      NSCLC in vitro.

PMID- 27698795
TI  - Whole-exome sequencing identifies variants in invasive pituitary adenomas.
AB  - Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion
      or malignant behavior in pituitary adenomas remains challenging. The objective of
      the present study was to identify the genetic abnormalities associated with
      invasion in sporadic pituitary adenomas. In the present study, the exomes of six
      invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA)
      were sequenced by whole-exome sequencing. Variants were confirmed by
      dideoxynucleotide sequencing, and candidate driver genes were assessed in an
      additional 28 pituitary adenomas. A total of 15 identified variants were mainly
      associated with angiogenesis, metabolism, cell cycle phase, cellular component
      organization, cytoskeleton and biogenesis immune at a cellular level, including
      13 variants that occurred as single nucleotide variants and 2 that comprised of
      insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical
      region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline-rich
      protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2),
      PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F
      actin binding protein and zinc finger protein 717 in IPA specimens were 50%
      decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and
      SPANXN2 mRNA levels in IPA specimens were approximately four-fold lower compared
      with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast,
      the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7
      (EGFL7), low density lipoprotein receptor-related protein 1B and dynein,
      axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA
      specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased
      PRDM2 expression was associated with tumor recurrence. The findings of the
      present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary
      adenomas are modifiers of tumorigenesis, and most likely contribute to the
      development of oncocytic change and to the invasive tumor phenotype.

PMID- 27698796
TI  - Mechanism analysis of colorectal cancer according to the microRNA expression
      profile.
AB  - The present study aimed to identify specific microRNAs (miRs) and their predicted
      target genes to clarify the molecular mechanisms of colorectal cancer (CRC). An
      miR expression profile (array ID, GSE39833), which consisted of 88 CRC samples
      with various tumor-necrosis-metastasis stages and 11 healthy controls, was
      downloaded from the Gene Expression Omnibus database. Subsequently, the
      differentially expressed miRs and their target genes were screened. Gene Ontology
      and Kyoto Encyclopedia of Genes and Genomes pathways of target genes were
      analyzed using the Database for Annotation Visualization and Integrated
      Discovery. A protein-protein interaction (PPI) network of the target genes was
      constructed using the Search Tool for the Retrieval of Interacting Genes
      database. The present study identified a total of 18 differentially expressed
      miRs (upregulated, 8; downregulated, 10) in the sera of the CRC patients compared
      with the healthy controls. Of these, 3 upregulated (let-7b, miR-1290 and miR-126)
      and 2 downregulated (miR-16 and miR-760) differentially expressed miRs and their
      target genes, including cyclin D1 (CCND1), v-myc avian myelocytomatosis viral
      oncogene homolog (MYC), phosphoinositide-3-kinase, regulatory subunit 2 (beta)
      (PIK3R2) and SMAD family member 3 (SMAD3), were significantly enriched in the CRC
      developmental pathway. All these target genes had higher node degrees in the PPI
      network. In conclusion, let-7b, miR-1290, miR-126, miR-16 and miR-760 and their
      target genes, CCND1, MYC, PIK3R2 and SMAD3, may be important in the molecular
      mechanisms for the progression of CRC.

PMID- 27698797
TI  - Antitumor effects of the hyaluronan inhibitor 4-methylumbelliferone on pancreatic
      cancer.
AB  - Hyaluronan (HA) is a major component of the extracellular matrix (ECM), and
      influences tumor invasion and metastasis. In a previous study, the present
      authors reported for the first time that 4-methylumbelliferone (MU) inhibited HA
      synthesis and suppressed tumor growth. However, the localization of HA and the
      changes in ECM morphology caused by MU in pancreatic cancer remain to be examined
      in detail. In the present study, the cytotoxicity of MU and its effect on
      cellular proliferation was evaluated in the human pancreatic cancer cell line MIA
      PaCa-2. The amount of HA synthesized and the retention of HA around the cells
      were quantitatively and immunohistochemically analyzed in vitro and in vivo.
      Structural changes in the ECM in the tumor tissue were investigated using an
      electron microscope. MU treatment led to a decrease in extracellular HA
      retention, as evidenced by a particle exclusion assay and immunohistochemical
      staining. Cell proliferation was suppressed by MU in a dose-dependent manner. The
      release of lactate dehydrogenase into the culture medium due to damage to the
      cellular membrane did not increase following MU administration. In tumor
      inoculated mice, MU suppressed any increase in tumor volume and decreased the
      quantity of HA. Electron microscopy revealed that MU attenuated the intercellular
      space and caused it to be less cohesive. These data indicate that MU inhibits HA
      synthesis and reduces the amount of HA in the ECM while exhibiting no obvious
      cytotoxic effect. These findings suggest that MU has potential as a novel
      therapeutic agent for pancreatic cancer.

PMID- 27698799
TI  - Expression of cyclooxygenase-2 in cervical cancer is associated with
      lymphovascular invasion.
AB  - Cyclooxygenase-2 (COX-2) is associated with carcinogenesis and tumor progression.
      The current study analyzed the effect of COX-2 expression in patients with
      invasive squamous cervical cancer. Tissue samples from 123 cervical cancer
      patients were collected for a retrospective analysis using immunohistochemistry
      (IHC) with an antibody against COX-2. The clinical and survival data of the
      patients were analyzed. Positive staining for COX-2 (defined as an
      immunoreactivity score of >=4) was detected in 28 patients (23%), with
      significantly higher percentages of staining in tumor cells compared with
      peritumoral stroma cells (P<0.001). COX-2 expression was significantly associated
      with lymphovascular space invasion (LVSI; P=0.017). The association of COX-2
      expression with LVSI suggests a possible effect of COX-2 on tumor progression in
      cervical cancer. Further studies including larger patient collectives are
      required in order to perform analyses of clinical subgroups and patient survival.

PMID- 27698798
TI  - Celecoxib exhibits an anti-gastric cancer effect by targeting focal adhesion and
      leukocyte transendothelial migration-associated genes.
AB  - Gastric cancer (GC) is a prevalent cancer, which remains incurable, and therefore
      requires an alternative treatment method. Celecoxib is a nonsteroidal anti
      inflammatory drug that targets cyclooxygenase-2, and exhibits anticancer effects.
      The present study aimed to investigate the anti-GC mechanism of celecoxib using
      bioinformatics methods. Gene expression datasets GSE56807 (GC tissues and normal
      gastric tissues) and GSE54657 (celecoxib-treated and non-treated human GC
      epithelial AGS cells) were downloaded from the Gene Expression Omnibus database.
      Two groups of differentially expressed genes (DEGs) were identified using limma
      package in R language. The criterion for GSE56807 was a false discovery rate of
      <0.05, while that for GSE54657 was P<0.01. Overlapping DEGs from the two datasets
      were screened out. Subsequently, pathway enrichment analysis was performed using
      Database for Annotation, Visualization and Integrated Discovery software (P<0.1;
      gene count >=2). In addition, the protein-protein interactions (PPIs) among the
      overlapped DEGs were obtained based on IntAct, Database of Interacting Proteins,
      Biomolecular Interaction Network Database and Human Protein Reference Database.
      Finally, a PPI network was visualized using Cytoscape software. A total of 137
      overlapped DEGs were obtained, and DEGs with opposite regulation directions in
      the two datasets were significantly enriched in focal adhesion and leukocyte
      transendothelial migration. Subsequently, a PPI network of overlapped DEGs was
      constructed. Comprehensively, a total of 8 key DEGs [cysteine and glycine rich
      protein 1 (CSRP1), thrombospondin 1 (THBS1), myosin light chain 9 (MYL9), filamin
      A (FLNA), actinin alpha 1 (ACTN1), vinculin (VCL), laminin subunit gamma 2
      (LAMC2) and claudin 1 (CLDN1)] were upregulated in GC tissues and downregulated
      in celecoxib-treated cells. In conclusion, celecoxib may exhibit anti-GC effects
      by suppressing the expression of CSRP1, THBS1, MYL9, FLNA, ACTN1, VCL, LAMC2 and
      CLDN1, and inhibiting leukocyte transendothelial migration and focal adhesion.
      However, relevant experiments are required to confirm the conclusion of the
      present study.

PMID- 27698800
TI  - High expression of lncRNA PVT1 promotes invasion by inducing epithelial-to
      mesenchymal transition in esophageal cancer.
AB  - The long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) has
      been identified as an oncogene in numerous diseases, and aberrant lncRNA PVT1
      expression has been associated with the development of cancer. However, the
      underlying mechanism by which lncRNA PVT1 affects cell invasion in esophageal
      cancer has been not demonstrated. In the current study, the expression of lncRNA
      PVT1 was found to be increased in esophageal cancer specimens (n=77) by reverse
      transcription-quantitative polymerase chain reaction, and was correlated with
      tumor stage (P=0.009) and metastasis (P<0.001). In vitro, by using transwell
      assay, upregulation of lncRNA PVT1 promoted the invasion of TE-1 esophageal
      cancer cells; while downregulation of lncRNA PVT1 inhibited Eca-109 cell
      invasion. In addition, western blot analysis indicated that upregulation of
      lncRNA PVT1 may induce epithelial-to-mesenchymal transition (EMT) by regulating
      the expression levels of EMT markers (E-cadherin, N-cadherin and vimentin). In
      conclusion, lncRNA PVT1 is able to regulate the invasion of esophageal cancer
      cells by inducing EMT.

PMID- 27698801
TI  - Combined use of free light chain and heavy/light chain ratios allow diagnosis and
      monitoring of patients with monoclonal gammopathies: Experience of a single
      institute, with three exemplar case reports.
AB  - Monoclonal gammopathies are characterized by serum monoclonal component (MC) plus
      an intact immunoglobulin and a free light chain (FLC), or a combination of both.
      The measurement of FLC with Freelite(r) is the standard practice recommended by
      International Myeloma Working Group guidelines. Recently, Hevylite(r) heavy/light
      chains (HLC) assays were introduced to specifically target junctional epitopes
      between the heavy and light chains of intact immunoglobulins, allowing the
      independent quantification of the involved (MC) and uninvolved (polyclonal
      immunoglobulin background) HLC isotype. Between January 2012 and March 2014, 90
      patients were examined: 49 multiple myeloma (MM), 6 smoldering MM (SMM) and 35
      monoclonal gammopathy of undetermined significance (MGUS). Of these 90 patients,
      300 samples were collected at different times. The diagnostic and monitoring
      contribution of Hevylite A and G assays was assessed in all 90 patients examined.
      Additionally, 3 representative cases were selected. The Hevylite absolute values
      and ratio demonstrated high sensitivity and specificity with respect to serum
      protein electrophoresis and serum immunofixation. The combined use of Hevylite A
      and G with Freelite was particularly useful in dubious cases with more than one
      MC or with co-migrating components, as well as in the course of monitoring to
      assess the independent change of FLC and HLC, possibly reflecting the presence of
      clonal heterogeneity in the cohort. From this study, it can be concluded that FLC
      and HLC are independent, useful markers to monitor the MC and to assess with
      greater specificity and sensitivity the effect of therapy, thereby providing
      clinical support. Further studies are required to assess the prognostic potential
      of Hevylite in MGUS and SMM.

PMID- 27698802
TI  - Identification of genes involved in Epstein-Barr virus-associated nasopharyngeal
      carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is the most common cancer originating from the
      nasopharynx, and can be induced by infection with Epstein-Barr virus (EBV). To
      study the mechanisms of EBV-associated NPC, a microarray of the GSE12452 dataset
      was analyzed. GSE12452 was downloaded from Gene Expression Omnibus and consisted
      of 31 NPC samples and 10 normal healthy nasopharyngeal tissue samples. The
      differentially-expressed genes (DEGs) were screened using the linear models for
      microarray data package in R. Using Database for Annotation, Visualization and
      Integrated Discovery software, potential functions of the DEGs were predicted by
      Gene Ontology and pathway enrichment analyses. With the information from the
      Search Tool for the Retrieval of Interacting Genes/Proteins database, the protein
      protein interaction (PPI) network was visualized by Cytoscape. Furthermore,
      modules of the PPI network were searched using ClusterONE in Cytoscape. A total
      of 951 DEGs were screened in the NPC samples compared with the normal healthy
      nasopharyngeal tissue samples. Function enrichment indicated that the upregulated
      genes were associated with the cell cycle, cytoskeleton organization and DNA
      metabolism. Meanwhile, the downregulated genes were mainly associated with cell
      differentiation, hormone metabolism, inflammatory response and immune response.
      PPI networks for the DEGs suggested that upregulated mitotic arrest deficient 2
      like 1 (MAD2L1; degree=133), proliferating cell nuclear antigen (PCNA;
      degree=125) and cyclin B1 (CCNB1; degree=115), and downregulated member A1 of
      aldehyde dehydrogenase 1 (ALDH1A1; degree=15) may be of great importance as they
      exhibited higher degrees on interaction. Mucin 1 (MUC1) was a key node of module
      4. Overall, the study indicated that MAD2L1, CCNB1, PCNA, ALDH1A1 and MUC1 may
      have a correlation with EBV-associated NPC.

PMID- 27698803
TI  - Expression and potential correlation among Forkhead box protein M1, Caveolin-1
      and E-cadherin in colorectal cancer.
AB  - The aim of the present study was to investigate the expression and functions of
      Forkhead box protein M1 (FoxM1), Caveolin-1 (Cav-1) and E-cadherin in colorectal
      cancer (CRC), and to determine the correlations among these proteins in CRC
      development and progression. The protein expression of FoxM1, Cav-1 and E
      cadherin was identified using a human CRC and normal tissue microarray. A
      standard immunohistochemistry assay was performed employing anti-FoxM1, anti-Cav
      1 and anti-E-cadherin antibodies. The clinicopathological significance of FoxM1,
      Cav-1 and E-cadherin in CRC was determined, and correlations were investigated
      between FoxM1 and Cav-1, FoxM1 and E-cadherin, Cav-1 and E-cadherin,
      respectively. The level of FoxM1, Cav-1 and E-Cadherin protein expression in CRC
      was found to be associated with pathological grade, tumor clinical stages and the
      presence of metastasis, respectively. Elevated expression of FoxM1 and Cav-1 was
      observed in the CRC tissues, and a significant correlation was found between the
      two proteins in CRC. However, it was also observed that FoxM1 was overexpressed
      while E-cadherin expression was low, indicating that there was a negative
      correlation between FoxM1 expression and E-cadherin expression. Moreover, there
      was also a negative correlation between Cav-1 and E-cadherin expression. Overall,
      the elevated expression of FoxM1 and Cav-1 in a human CRC microarray provided
      novel clinical evidence to elucidate the fact that they may play a critical role
      in the development and progression of CRC by negatively regulating E-cadherin
      expression. Furthermore, the positive correlation between FoxM1 and Cav-1
      suggested that the proteins may constitute a novel signaling pathway in human
      CRC.

PMID- 27698804
TI  - Entrance of the Tat protein of HIV-1 into human uterine cervical carcinoma cells
      causes upregulation of HPV-E6 expression and a decrease in p53 protein levels.
AB  - The infection of uterine cervical epithelial cells by oncogenic, high-risk human
      papilloma viruses (HR-HPVs) may lead to the development of cervical carcinoma. Of
      note, the incidence of this tumor is significantly increased in women infected by
      both HR-HPV and human immunodeficiency virus (HIV)-1. In this regard, previous
      studies have linked the HIV-1 Tat protein, a trans-activator of viral gene
      expression, to the pathogenesis of HIV-associated malignancies. In particular, it
      has been shown that upon its release by acutely infected cells, Tat protein can
      enter human cells, thus modifying their phenotype. Based on these findings, the
      present study evaluated whether extracellular Tat protein could be taken up by
      human uterine cervical carcinoma cells, and whether this could affect the
      expression of HPV (E6 or E7) or cellular (p16 or p53) molecules, which are key to
      cervical carcinoma development or progression. The results indicated that
      extracellular, biologically active HIV-1 Tat protein is taken up by human uterine
      cervical carcinoma cells, and that this is followed by an increase in the
      expression of the E6 protein of HPV, and by a reduction in the protein levels of
      the cellular oncosuppressor p53. Since p53 loss is associated with cell
      dedifferentiation and immortalization, these findings suggest a possible link
      between extracellular Tat protein and the high incidence and clinical
      aggressiveness of uterine cervical carcinoma observed in HIV/HPV doubly infected
      women.

PMID- 27698805
TI  - Genetic landscape of a case of extraovarian peritoneal serous papillary
      carcinoma.
AB  - The present report aimed to study genetic alterations underlying extraovarian
      peritoneal serous papillary carcinoma (EPSPC), which have not previously been
      systematically investigated. A case of EPSPC was identified, and its genetic
      alterations were assessed by combining comparative genomic hybridization and
      whole-exome sequencing technologies to investigate the genomic landscape,
      including copy number variations and mutations in EPSPC. It was found that a
      large number of germline mutations were present, which may have predisposed the
      patient to the occurrence of this disease. Copy number gains were found in a
      range of chromosomes, including 4q, 5q, 8q, 10q, 15q, 16p, 18q, 20p, 20q and Xq.
      Large-scale copy number loss occurred in chromosomes 2p, 13q, 16q, 17p and 17q.
      Through use of whole-exome sequencing, germline mutations were widely found that
      were associated with cancer development, including mutations in the BRCA1, DNA
      repair associated (BRCA1), BRCA2, tumor protein 53, erb-b2 receptor tyrosine
      kinase 2, matrix metalloproteinases and ADAM metallopeptidase domain-containing
      genes. In addition, 165 somatic mutations, including 52 missense mutations and 7
      short insertions or deletions, were also identified. In summary, the EPSPC was
      undergoing profound genomic rearrangement and somatic mutation, which may have
      led to its initiation and development, and the present study discussed the
      genetic basis of this highly malignant cancer.

PMID- 27698807
TI  - Negative pathology of ureteral carcinoma significantly delaying the diagnosis of
      the primary tumor of osteoblastic metastases: A case report and review of the
      literature.
AB  - Ureteral urothelial carcinoma (UC) is a rare malignant tumor. The most common
      clinical manifestations of ureteral UC are hematuria, increased urinary
      frequency, dysuria and pain. The diagnosis of ureteral UC is made via
      radiography, endoscopy and pathology. Although osteoblastic destruction is
      usually observed in metastasis of prostate cancer, UC can also be a reason for
      osteoblastic metastasis. The present study reports the case of a 66-year-old man
      presenting with osteoblastic metastases, in which the primary tumor was finally
      diagnosed as a ureteral UC. However, the lack of pathological evidence
      significantly delayed the diagnosis of the primary tumor (>6 months), even though
      the results of radiographic examination, and the type and mode of bone metastases
      significantly suggested a ureteral UC. The case reveals that a suitable screening
      test should be recommended for patients at high risk due to the possibility of a
      negative pathology result for ureteral UC. Additionally, a more efficient
      diagnostic method is required. Moreover, the possibility of new diagnostic
      criterion that do not rely on the pathology of primary foci in ureteral UC should
      be considered in future.

PMID- 27698806
TI  - Matrix metalloproteinase expression and molecular interaction network analysis in
      gastric cancer.
AB  - Gastric cancer (GC) is one of the most common types of cancer of the digestive
      tract. Invasion of tumor cells into surrounding tissue and metastasis are among
      the most significant checkpoints in tumor progression. It is known that matrix
      metalloproteinases (MMPs) are involved in these processes; however, knowledge of
      their molecular interaction networks is still limited. Investigation of these
      networks could provide a more comprehensive picture of the function of MMPs in
      tumorigenesis. Furthermore, it could be used to develop new approaches to
      targeted anticancer therapy. In this study, we performed microarray analysis, and
      1666 genes that were aberrantly expressed in GC tissues were identified (fold
      change >2, P<0.05). In addition, quantitative polymerase chain reaction analysis
      has confirmed that MMP1, MMP3, MMP7, MMP10, MMP11 and MMP12 expression is
      upregulated in GC. In addition, the MMP3 expression level was negatively
      correlated with GC differentiation (P<0.05). By integrating the microarray
      information and BioGRID and STRING databases, we constructed an MMP-related
      molecular interaction network and observed that 18 genes (including MMPs) were
      highly expressed in GC tissues. The most enriched of these 18 genes in the Gene
      Oncology (GO) and pathway analysis were in extracellular matrix disassembly (GO
      biological process) and extracellular matrix-receptor interaction (KEGG pathway),
      which are closely correlated with cancer invasion and metastasis. Collectively,
      our results suggest that the MMP-related interaction network has a role in GC
      progression, and therefore further studies are required in order to investigate
      these network interactions in tumorigenesis.

PMID- 27698808
TI  - Increase of T and B cells and altered BACH2 expression patterns in bone marrow
      trephines of imatinib-treated patients with chronic myelogenous leukaemia.
AB  - The effect of imatinib on T and B cells in patients with chronic myelogenous
      leukaemia (CML) is not well understood. An upregulation of the transcription
      factor Broad-complex-Tramtrack-Bric-a-Brac and Cap'n'collar 1 bZip transcription
      factor 2 (BACH2), which is involved in the development and differentiation of B
      cells, was demonstrated in a CML cell line treated with imatinib. The present
      study retrospectively analysed the expression and distribution of cluster of
      differentiation (CD)3, CD20 and BACH2 (per 1,000 cells), as well as the co
      expression of CD20 and BACH2, using immunohistochemistry in serial bone marrow
      trephines obtained from 14 CML patients treated with imatinib in comparison to 17
      patients with newly diagnosed CML and 6 control trephines. Bone marrow trephines
      of CML patients in remission under imatinib therapy exhibited significantly
      higher numbers of CD3 and CD20 infiltrates (partly ordered in aggregates)
      compared with patients with newly diagnosed CML and control individuals.
      Similarly, nuclear expression of BACH2 in granulopoietic cells was increased in
      CML patients treated with imatinib, which may represent the histological
      correlate of the positive treatment effect. Furthermore, since BACH2 is involved
      in B cell development, its altered expression patterns by imatinib may be one
      explanation for high B cell numbers, as revealed by CD20/BACH2 (nuclear)-positive
      cells. As the present data are preliminary, future prospective studies are
      required to assess the prognostic and predictive role of BACH2 in patients with
      CML under targeted therapy.

PMID- 27698809
TI  - Expression and prognostic significance of CTBP2 in human gliomas.
AB  - Deregulated expression of C-terminal-binding protein 2 (CTBP2) has been observed
      previously in a number of tumors, such as hepatocellular carcinoma and prostatic
      cancer, in the colorectal cancer SW480 cell line and in the human embryonic
      kidney 293 cell line. In the present study, western blot analysis and
      immunohistochemistry were performed to investigate whether gliomas exhibit
      deregulated CTBP2 expression. Kaplan-Meier survival analyses were performed to
      evaluate the associations between CTBP2 expression, clinicopathological data and
      patient survival in glioma patients. The results revealed that CTBP2 expression
      was significantly upregulated in high grade glioma tissues compared with that in
      low grade glioma and normal brain tissues. Furthermore, increased CTBP2
      expression in gliomas was significantly associated with a higher World Health
      Organization (WHO) tumor grade (P<0.005) and poorer disease-specific survival
      (P<0.005). In conclusion, these results suggest that CTBP2 may act as an
      intrinsic regulator of progression in glioma cells and thus may serve as an
      important prognostic factor for the disease.

PMID- 27698810
TI  - Association between SET expression and glioblastoma cell apoptosis and
      proliferation.
AB  - Glioblastoma multiforme (GBM) was one of the first cancer types systematically
      studied at a genomic and transcriptomic level due to its high incidence and
      aggressivity; however, the detailed mechanism remains unclear, even though it is
      known that numerous cytokines are involved in the occurrence and development of
      GBM. The present study aimed to determine whether the SET gene has a role in
      human glioblastoma carcinogenesis. A total of 32 samples, including 18 cases of
      glioma, 2 cases of meningioma and 12 normal brain tissue samples, were detected
      using the streptavidin-peroxidase method through immunohistochemistry. To reduce
      SET gene expression in U251 and U87MG cell lines, the RNA interference technique
      was used and transfection with small interfering (si)RNA of the SET gene was
      performed. Cell apoptosis was detected by flow cytometry, cell migration was
      examined by Transwell migration assay and cell proliferation was determined by
      Cell Counting Kit-8. SET, Bcl-2, Bax and caspase-3 mRNA and protein expression
      levels were detected by reverse transcription-quantitative polymerase chain
      reaction and western blot analysis, respectively. Positive protein expression of
      SET was observed in the cell nucleus, with the expression level of SET
      significantly higher in glioma tissues compared with normal brain tissue
      (P=0.001). Elevated expression of SET was significantly associated with gender
      (P=0.002), tumors classified as World Health Organization grade II (P=0.031), III
      (P=0.003) or IV (P=0.001), and moderately (P=0.031) or poorly differentiated
      (P=0.001) tumors. Compared with the negative and non-treatment (blank) control
      cells, SET gene expression was significantly inhibited (P=0.006 and P<0.001),
      cell apoptosis was significantly increased (P=0.001 and P<0.001), cell
      proliferation was significantly inhibited (P=0.002 and P=0.015), and cell
      migration was significantly decreased (P=0.001 and P=0.001) in siRNA-transfected
      U87MG-SET and U251-SET cells, respectively. In addition, mRNA and protein
      expression levels of Bcl-2 were significantly inhibited in U87MG-SET and U251-SET
      cells, while mRNA and protein expression levels of Bax and caspase-3 were
      significantly increased, compared with the two control groups. Thus, the current
      data suggests that SET may regulate the proliferation and apoptosis of
      glioblastoma cells by upregulating Bcl-2, and downregulating Bax and caspase-3.

PMID- 27698811
TI  - Expression of FoxM1 and the EMT-associated protein E-cadherin in gastric cancer
      and its clinical significance.
AB  - The aim of the present study was to investigate the expression of forkhead box M1
      (FoxM1) and E-cadherin in tissues of gastric cancer in order to reveal any
      correlation between FoxM1, E-cadherin and clinicopathological parameters. The
      association between FoxM1 and E-cadherin in the development and progression of
      gastric cancer was also investigated. The expression of FoxM1 and E-cadherin in
      gastric cancer and adjacent normal tissue on tissue microarray was detected using
      immunohistochemistry. The clinicopathological significance of FoxM1 and E
      cadherin in gastric cancer was explored, and the association between FoxM1 and E
      cadherin was further examined using statistical techniques. In gastric cancer
      tissues, the expression of FoxM1 and E-cadherin was strongly positive, but it was
      weak in normal gastric mucosa. Overexpression of FoxM1 was evident in gastric
      cancer, and was associated with poor tumor differentiation (P<0.05), advanced
      tumor state (P<0.05) and lymph node (or distant) metastasis (P<0.05), whereas E
      cadherin had the opposite effects. Furthermore, the correlation between FoxM1 and
      E-cadherin expression in gastric cancer tissue was negative. In conclusion, the
      high FoxM1 expression and low E-cadherin expression in gastric cancer tissue
      suggests that these proteins play a critical role in the development and
      progression of gastric cancer.

PMID- 27698812
TI  - Ultrasonic features of papillary thyroid microcarcinoma coexisting with a thyroid
      abnormality.
AB  - The present study aimed to investigate the value of ultrasonography in the
      diagnosis of papillary thyroid microcarcinoma (PTMC) coexisting with a thyroid
      abnormality, and to improve the accuracy of PTMC diagnosis. The ultrasonic
      features of 38 PTMC nodules coexisting with a thyroid abnormality and 56 thyroid
      benign nodules, obtained by surgical resection and confirmed by pathological
      analysis, were retrospectively analyzed. All masses were <= 1.0 cm in diameter.
      Ultrasonic features that were analyzed included the shape, aspect ratio,
      boundary, margin, echo, uniformity, presence or absence of microcalcification and
      enlargement of the lymph nodes, as well as the blood flow of the nodules.
      Furthermore, the sensitivity, specificity and accuracy of ultrasonography for the
      diagnosis of PTMC were obtained. The following ultrasonic features of thyroid
      nodules were significantly (P<0.05) associated with PTMC coexisting with a
      thyroid abnormality: An irregular shape; an aspect ratio of >= 1; an unclear
      boundary; blurred margins; internal heterogeneous hypoechogenicity; and
      microcalcification. Therefore, thyroid nodules with these ultrasonic
      characteristics coexisting with a thyroid abnormality may be suspected as
      malignant PTMC. The present study demonstrated that ultrasound-guided biopsies
      are necessary to prevent misdiagnosis of PTMC. The sensitivities of enlarged neck
      lymph nodes and abundant blood flow are so low that they may be considered as
      references for the differentiation of PTMC from benign nodules.

PMID- 27698813
TI  - Screening glioma stem cells in U251 cells based on the P1 promoter of the CD133
      gene.
AB  - Cluster of differentiation (CD)133 is an important cell surface marker of glioma
      stem cells (GSCs). The transcription of the CD133 gene is controlled by five
      alternative promoters (P1, P2, P3, P4 and P5), which are expressed in a tissue
      specific manner. In the present study, gene recombination technology was used to
      construct two types of gene expression vectors that contained the P1 promoter of
      the CD133 gene, which regulated either the neomycin-resistance gene or the herpes
      simplex virus thymidine kinase (HSV-TK) gene. Following the stable transfection
      of U251 glioblastoma cells with these two gene vectors, the cells expressing the
      P1 promoter that regulated the neomycin-resistance gene were named CD133 (+)
      cells, while the cells expressing the P1 promoter regulating the HSV-TK gene were
      called CD133 (-) cells. The expression of CD133 was detected by flow cytometry
      and reverse transcription-quantitative polymerase chain reaction. The 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess
      cell proliferation ability, while the cell cycle was analyzed by flow cytometry,
      and a clone formation test was performed to evaluate the invasive capability of
      the cells. The results demonstrated that, due to CD133 expression, the cell
      proliferation ability and the invasive capability of CD133 (+) cells were
      significantly higher than those of CD133 (-) cells. In conclusion, the present
      study successfully established a novel method of screening GSCs in U251 cells
      based on the P1 promoter of the CD133 gene.

PMID- 27698814
TI  - Effect of API-1 and FR180204 on cell proliferation and apoptosis in human DLD-1
      and LoVo colorectal cancer cells.
AB  - The activation of the phosphatidylinositol-3 kinase/v-akt murine thymoma viral
      oncogene homolog (Akt) and mitogen activated protein kinase kinase/extracellular
      signal-regulated kinase (ERK) pathways are implicated in the majority of cancers.
      Selective inhibition of Akt and ERK represents a potential approach for cancer
      therapy. Therefore, the present study aimed to investigate the apoptotic and anti
      proliferative effects of the novel and selective Akt inhibitor 4-amino-5,8
      dihydro-5-oxo-8-beta-D-ribofuranosyl-pyrido[2,3-d]pyrimidine-6-carboxamide (API
      1) and selective ERK1/2 inhibitor FR180204 (FR) alone and in combination on
      colorectal cancer (CRC) cells (DLD-1 and LoVo). In addition, the effects of API-1
      and FR on Akt and ERK signaling pathways were also investigated. The effects of
      the agents on DLD-1 and LoVo cells were evaluated in terms of cell viability,
      cytotoxicity, DNA synthesis rate, DNA fragmentation and caspase-3 activity
      levels. In addition, quantitative reverse transcription-polymerase chain reaction
      and western blot analysis were performed to examine relevant mRNA and protein
      levels. The present study observed that the combination of FR with API-1 resulted
      in significant apoptosis and cytotoxicity compared with any single agent alone in
      a time-dependent manner in these cells. Also, treatment with FR and API-1 in
      combination decreased the expression levels of B-cell lymphoma-2 (BCL2), Bcl-2
      like1, cyclin D1 and cMYC, and increased the expression levels of BCL2-associated
      X protein and BCL2 antagonist/killer via phosphorylated Akt and phosphorylated
      ERK1/2 downregulation. The combination of Akt and ERK1/2 inhibitors resulted in
      enhanced apoptotic and anti-proliferative effects against CRC cells. The present
      study hypothesizes that the combination of FR and API-1 in CRC cells may
      contribute toward potential anti-carcinogenic effects. Additional analyses using
      other cancer cell lines and animal models are required to confirm these findings
      in vitro and in vivo.

PMID- 27698815
TI  - Clinical analysis of 47 cases of solitary fibrous tumor.
AB  - The aim of the present study was to summarize the clinical manifestations,
      diagnosis, treatment, and prognosis of solitary fibrous tumor (SFT). In total, 47
      cases of SFTs diagnosed by postoperative pathology between January 2002 and
      September 2014 were retrospectively reviewed, and the general information,
      clinical manifestations, imaging techniques, treatment, pathology and follow-up
      findings were analyzed. Of the 47 patients, clinical characteristics were
      collected in 37 cases (18 men and 19 women; mean age, 44.1 years; age range, 13
      72 years). The maximum diameters of the tumors were 1.5-25 cm, with a mean
      diameter of 8.8 cm. The symptoms were various and non-specific. Imaging
      examinations following iodinated contrast administration showed the SFTs to be
      well-defined, cystic or solid mass and enhanced. On color Doppler ultrasound,
      SFTs were described as hypoechoic, clear, irregular masses. All patients
      underwent surgical resection, and SFT was diagnosed by postoperative pathological
      and immunohistochemical examination. Of the 47 patients, 25 received complete
      follow-up of 5-130 months, with a median follow-up period of 35.2 months, that
      included a color Doppler ultrasound or computed tomography (CT) scan every 6-12
      months. At the end of the follow-up period all patients were alive and healthy,
      with the exception of one patient, who presented with recurrence 15 months after
      surgery. The findings of the present study showed SFT to be a rare systemic
      disease with no particular clinical manifestations. In the cases reviewed in the
      present study, CT, magnetic resonance imaging scans and color Doppler ultrasound
      were important for the diagnosis of SFT, while the definitive diagnosis relied on
      pathological and immunohistochemical examinations. Surgery, the primary treatment
      for SFT, was performed, and, following complete removal of the tumor, the
      prognosis was favorable.

PMID- 27698816
TI  - Evaluation of automated breast volume scanner for breast conservation surgery in
      ductal carcinoma in situ.
AB  - The present is a retrospective study examining the use of automated breast volume
      scanner (ABVS) for guiding breast conservation surgery in ductal carcinoma in
      situ (DCIS). A total of 142 patients with pathologically confirmed DCIS were
      initially included in the study. The patients underwent preoperative examination
      by conventional ultrasound and by ABVS. The BI-RADS category system was used to
      identify benign and malignant lesions, after which breast conservation surgery
      was performed, and the therapeutic effects were compared. DCIS lesions were found
      in each quadrant of the breasts. Typical symptoms included: Duct ectasia and
      filling in 23 cases, mass (mainly solid, occasionally cystic, with or without
      calcification) in 38 cases, hypoechoic area (with or without calcification) in 33
      cases, calcifications (simple) in 23 cases, and architectural distortion in 17
      cases. In addition, 110 cases (82.1%) were detected as grade >=4 according to the
      BI-RADS category, and 92 cases (68.7%) were considered malignant lesions
      following conventional ultrasound scanning. The detection rate of ABVS was
      significantly higher than that of conventional ultrasound (chi2=268.000,
      P<0.001). The average tumor diameter was 2.5+/-0.8 cm using ABVS and 2.0+/-0.9 cm
      using conventional ultrasound (the former being significantly higher than the
      latter; t=6.325, P=0.034). Eight patients (5.6%) had recurrences of the cancer,
      and the tumor diameter in the 8 patients was significantly larger using ABVS as
      compared to conventional ultrasound. In the diagnosis of DCIS, ABVS was superior
      to conventional ultrasound scanner in guiding breast conservation surgery and
      predicting recurrence. However, large-scale studies are required for confirmation
      of the findings.

PMID- 27698817
TI  - Stem cell growth factor receptor in canine vs. feline osteosarcomas.
AB  - Osteosarcoma is considered the most common bone cancer in cats and dogs, with
      cats having a much better prognosis than dogs, since the great majority of dogs
      with osteosarcoma develop distant metastases. In search of a factor possibly
      contributing to this disparity, the stem cell growth factor receptor KIT was
      targeted, and the messenger (m)RNA and protein expression levels of KIT were
      compared in canine vs. feline osteosarcomas, as well as in normal bone. The mRNA
      expression of KIT was quantified by reverse transcription-quantitative polymerase
      chain reaction, and was observed to be significantly higher in canine (n=14) than
      in feline (n=5) osteosarcoma samples (P<0.001). KIT protein expression was
      evaluated by immunohistochemistry, which revealed that 21% of canine osteosarcoma
      samples did not exhibit KIT staining in their neoplastic cells, while in 14% of
      samples, a score of 1 (<10% positive tumour cells) was observed, and in 50% and
      14% of samples, a score of 2 (10-50% positivity) and 3 (>50% positivity),
      respectively, was observed. By contrast, the cancer cells of all the feline bone
      tumour samples analysed were entirely negative for KIT. Notably, canine and
      feline osteocytes of healthy bone tissue lacked any KIT expression. These results
      could be the first evidence that KIT may be involved in the higher aggressiveness
      of canine osteosarcoma compared with feline osteosarcoma.

PMID- 27698818
TI  - The HIV-protease inhibitor saquinavir reduces proliferation, invasion and
      clonogenicity in cervical cancer cell lines.
AB  - Innovative therapies in cervical cancer (CC) remain a priority. Recent data
      indicate that human immunodeficiency virus (HIV)-protease inhibitors used in
      highly active antiretroviral therapy can exert direct antitumor activities also
      in HIV-free preclinical and clinical models. The aim of the present study was to
      evaluate the antineoplastic effects of various HIV-protease inhibitors
      (indinavir, ritonavir and saquinavir) on primary and established CC cell lines.
      Two CC cell lines established in our laboratory and four commercially available
      CC cell lines were treated with indinavir, ritonavir and saquinavir at different
      concentrations and for different times. Proliferation, clonogenicity and
      radiosensitivity were evaluated by crystal violet staining. Proteasomal
      activities were assessed using a cell-based assay and immunoblotting. Cell cycle
      was analyzed by propidium iodide staining and flow cytometric analysis. Invasion
      was tested with Matrigel chambers. A t-test for paired samples was used for
      statistical analysis. In all cell lines, saquinavir was more effective than
      ritonavir in reducing cell proliferation and inhibiting proteasomal activities
      (P<=0.05). Conversely, indinavir exerted a negligible effect. The saquinavir
      concentrations required to modulate the proteasome activities were higher than
      those observed to be effective in inhibiting cell proliferation. In HeLa cells,
      saquinavir was strongly effective in inhibiting cell invasion and clonogenicity
      (P<=0.05) at concentrations much lower than those required to perturb proteasomal
      activities. Saquinavir did not contribute to increase the sensitivity of HeLa
      cells to X-rays. In conclusion, the present results demonstrate that saquinavir
      is able to significantly reduce cell proliferation, cell invasion and
      clonogenicity in a proteasome-independent manner in in vitro models of CC, and
      suggest that saquinavir could be a promising CC therapeutic agent.

PMID- 27698819
TI  - Significance of stem cell marker Nanog gene in the diagnosis and prognosis of
      lung cancer.
AB  - The aim of the present study was to analyze the stem cell marker, Nanog gene, for
      the diagnosis and prognosis of lung cancer cases, and to study its application in
      the diagnosis of lung cancer. In total, 100 patients diagnosed with lung cancer
      between April, 2013 and May, 2015 were included in the present study. The
      patients were randomly divided into group A (lung cancer) and group B (squamous
      cell lung carcinoma). RT-PCR was used to detect the cancer and adjacent tissues,
      and Nanog gene expression was detected in groups A and B in cells. The results
      showed that, analysis of Nanog gene expression in the two groups of patients
      varied to different degrees. There was no significant difference between the two
      groups with regard to age, gender, disease stage and lymph node metastasis. Nanog
      gene expression in patients with carcinoma were significantly higher than that in
      the adjacent tissues (p<0.05). By contrast, differentiated and well
      differentiated carcinoma tissue showed a significantly higher Nanog gene
      expression than poorly differentiated and undifferentiated carcinoma (p<0.05).
      The expression of Nanog in normal cells was significantly higher than that in
      normal lung tissues and benign lesions in lung cancer stem cells. Nanog was
      highly expressed in CD44+ cells, and Nanog expression in lung cancer stem cells
      was significantly higher (p<0.05). In conclusion, for groups A (lung cancer) and
      B (squamous cell lung carcinoma) the Nanog gene expression was significantly
      higher. The data of the present study show that the patients with stage III and
      IV lung cancer had a higher Nanog gene expression. In addition, there was a
      higher expression of Nanog in lung cancer patients. By contrast, a lower degree
      of cell differentiation was associated with strong Nanog gene expression in lung
      cancer.

PMID- 27698820
TI  - Hepatocellular carcinoma stem cell-like cells are enriched following low-dose 5
      fluorouracil chemotherapy.
AB  - It has been proposed that cancer stem cells (CSCs) are involved in tumor
      resistance to chemotherapy and tumor relapse. The goal of the present study was
      to determine the effect of low-dose 5-fluorouracil (5-Fu) on enriched
      hepatocellular CSC-like cells. Increased cell motility and epithelial-mesenchymal
      transition were observed by migration assay in human hepatoblastoma PLC/RAF/5
      cells following 5-Fu treatment, as well as a significant enhancement in their
      sphere-forming abilities. CSC-like cells were identified by side population cell
      analysis. The percentage of CSC-like cells in the surviving cells was greatly
      increased in response to 5-Fu. These findings indicate that low-dose 5-Fu
      treatment may efficiently enrich the CSC-like cell population in PLC/RAF/5 cells.

PMID- 27698821
TI  - Comparison of the accuracy of 99mTc-3P4-RGD2 SPECT and CT in diagnosing solitary
      pulmonary nodules.
AB  - The aim of the present study was to compare technetium-99m-(polyethylene glycol
      4)3-(Arg-Gly-Asp)2 (99mTc-3P4-RGD2) single-photon emission computed tomography
      (SPECT) and computed tomography (CT) in the noninvasive differentiation of
      solitary pulmonary nodules (SPNs). The present study prospectively investigated a
      consecutive series of 24 patients with SPN, who were newly diagnosed using
      radiography between September 2012 and January 2014. All patients underwent 99mTc
      3P4-RGD2 SPECT and CT scans using a dual-head variable-angle gamma-camera
      equipped with high-resolution collimators. A blinded panel of two thoracic
      radiologists for CT and three nuclear physicians for SPECT analyzed the images
      using a 5-grade scale. The SPECT images were also semi-quantitatively evaluated
      using tumor to non-tumor localization ratios (T/NT). The results were verified by
      pathological examination of the biopsy material obtained from each patient with
      SPN, and receiver operating characteristic (ROC) curves were generated from these
      results. The present results revealed that there were 17 malignant and 7 benign
      SPNs among the 24 patients with SPN. The mean size of the SPN was 2.1+/-0.6 cm.
      Sensitivity of visual analysis for SPECT and CT were 100.0 and 82.4%,
      respectively, and specificity was 71.4% for the two methods. When the T/NT SPECT
      semiquantitative analysis (ratio, 1.64) was used as a cut-off, the sensitivity
      and specificity of SPECT were 100.0 and 71.4%, respectively. The areas under the
      ROC curves were 0.840 for visual analysis of SPECT [95% confidence interval (CI),
      0.600-1.000], 0.849 for semiquantitative analysis of SPECT (95% CI, 0.618-1.000)
      and 0.815 for CT (95% CI, 0.626-1.000). In conclusion, the present results
      suggest that 99mTc-3P4-RGD2 SPECT is more accurate than CT in the detection of
      malignant SPN, and visual analysis appears to be sufficient for the
      characterization of SPN.

PMID- 27698822
TI  - Bioinformatics analysis of the molecular mechanism of diffuse intrinsic pontine
      glioma.
AB  - The present study aimed to elucidate key molecular mechanisms in the progression
      of diffuse intrinsic pontine glioma (DIPG). The gene expression profile GSE50021,
      which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was
      downloaded from the Gene Expression Omnibus database. The differentially
      expressed genes (DEGs) in the pediatric DIPG samples were identified. Gene
      Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome
      pathways of DEGs were enriched and analyzed. The protein-protein interaction
      (PPI) network of the DEGs was constructed and functional modules of the PPI
      network were disclosed using ClusterONE. A total of 679 DEGs (454 up- and 225
      downregulated) were identified in the pediatric DIPG samples. DEGs were
      significantly enriched in various GO terms, and KEGG and Reactome pathways. The
      PPI network of upregulated (153 nodes and 298 connections) and downregulated (71
      nodes and 124 connections) DEGs, and two crucial modules, were obtained.
      Downregulated genes in module 2, such as cholecystokinin (CCK), gastrin (GAST),
      adenylate cyclase 2 (brain) (ADCY2) and 5-hydroxytryptamine (serotonin) receptor
      7 (HTR7), were significantly enriched in the calcium signaling pathway, the
      neuroactive ligand-receptor interaction pathway and in GO terms, such as the G
      protein coupled receptor (GPCR) signaling pathway, while upregulated genes in
      module 1 were not enriched in any pathways or GO terms. CCK and GAST associated
      with the GPCR signaling pathway, HTR7 enriched in the neuroactive ligand-receptor
      interaction, and ADCY2 and HTR7 involved in the calcium signaling pathway may be
      key mechanisms playing crucial roles in the development and progression of DIPG.

PMID- 27698823
TI  - miRNA-335 and miRNA-182 affect the occurrence of tongue squamous cell carcinoma
      by targeting survivin.
AB  - The aim of the present study was to characterize the roles of two microRNAs
      (miRs) that have been reported to be differentially expressed in tongue squamous
      cell carcinoma (TSCC), miR-335 and miR-182. In total, 20 tumor tissue samples and
      20 corresponding adjacent non-cancerous samples were collected from patients with
      TSCC to measure the expression of miR-335 and miR-182 and the potential shared
      target of these miRs, survivin, using reverse transcription-quantitative
      polymerase chain reaction and western blotting. In the TSCC tissue samples,
      significantly decreased expression of the two miRs and increased expression of
      survivin were detected compared with adjacent non-cancerous controls.
      Subsequently, it was confirmed that survivin was the target gene of miR-335 and
      miR-182 using a luciferase assay in TSCC cells. In order to examine the function
      of miR-335 and miR-182 in the development of TSCC, TSCC cells were transiently
      transfected with the mimics of the two miRs, and it was confirmed that the
      introduction of miR-335 and miR-182 to cells suppressed the expression of
      survivin and markedly inhibited the proliferation of the TSCC cells. Furthermore,
      miR-335 and miR-182 were found to induce cell cycle arrest by suppressing the
      expression of survivin. The present study revealed a negative regulatory role of
      miR-335 and miR-182 in the proliferation of TSCC cells by targeting survivin, and
      miR-335 and miR-182 may be novel therapeutic targets for the treatment of TSCC.

PMID- 27698824
TI  - miR-101 inhibits glioma cell invasion via the downregulation of COX-2.
AB  - Glioma is the most common type of primary tumor of the central nervous system.
      The present study aimed to demonstrate the role of miR-101 and cyclooxygenase-2
      (COX-2) in the initiation and development of glioma. The expression of miR-101
      and COX-2 in normal and malignant human glial cells and tissues was determined by
      western blotting and quantitative polymerase chain reaction analysis. The role of
      miR-101 on COX-2 expression was evaluated by a dual-luciferase reporter assay.
      The effects of miR-101 and COX-2 in glioma cell proliferation and invasion was
      verified by CCK-8 test and Transwell assays, respectively. The present study
      demonstrated that miR-101 expression was downregulated while COX-2 was
      upregulated in glioma tissues and cells. Furthermore, transfection of miR-101
      significantly downregulated COX-2 expression in both U373 and U87 glioma cells.
      In addition, further experiments revealed that overexpression of miR-101 resulted
      in significant inhibition of the in vitro proliferation and migration of glioma
      cells, and the in vivo growth of established tumors. Direct downregulation of COX
      2 by transfection with corresponding small interfering RNA also inhibited the
      proliferation and invasion of glioma cells. These results indicate that
      downregulation of miR-101 is involved in the initiation and development of glioma
      via COX-2 upregulation.

PMID- 27698826
TI  - Effects of ZNF139 on gastric cancer cells and mice with gastric tumors.
AB  - Gastric cancer (GC) is the fourth most common type of cancer, worldwide. The
      major molecular factors associated with the pathogenesis of GC remain unclear.
      Previous studies found that zinc finger proteins are highly abundant in human
      eukaryotes and tissues, and play an important role in maintaining normal cellular
      functions and have an association with tumor initiation. In the current study,
      interference technology was used to silence the ZNF139 protein, a zinc finger
      protein that was previously found to be closely associated with GC. The results
      showed that cell viability and proliferation were inhibited in the Znf139
      knockdown of GC cells. Additional study found that the expression levels of B
      cell lymphoma-2 (Bcl-2) and survivin messenger RNAs and proteins were
      downregulated in Znf139-silenced cells, indicating that cells expression Znf139
      are able to induce the growth of tumor cells by mediating the apoptosis pathway.
      Further in vivo experiments showed that Znf139 knockdown downregulated the
      expression levels of Bcl-2 and survivin in mice. Overall, the in vitro and in
      vivo findings of the present study indicate that ZNF139 may be actively involved
      in the progression of GC.

PMID- 27698825
TI  - Glioma coexisting with angiographically occult cerebrovascular malformation: A
      case report.
AB  - Angiographically occult cerebrovascular malformation (AOVM) is a type of complex
      cerebrovascular malformation that is not visible on digital subtraction
      angiography (DSA). Vascular malformation coexisting with glioma is clinically
      rare, and glioma coexisting with AOVM is even more rare. To the best of our
      knowledge, the present study is the first to report glioma coexisting with AOVM
      in the literature. The present study reports a rare case of glioma coexisting
      with AOVM in a 30-year-old male patient. Computed tomography (CT) scan revealed
      calcification, hemorrhage and edema in the right frontal lobe. CT angiography
      revealed a vascular malformation in the right frontal lobe, which was not
      observed on DSA. Finally, glioma coexisting with AOVM was confirmed by 2.0T
      magnetic resonance imaging and postoperative pathological examination. The
      present patient had a positive outcome and no neurological dysfunctions during
      the 6-month follow-up subsequent to surgery.

PMID- 27698827
TI  - Prognostic significance of CD168 overexpression in colorectal cancer.
AB  - The expression of cluster of differentiation 168 (CD168), a cell surface receptor
      for hyaluronan, is associated with cancer progression and metastases. The aim of
      the present study was to analyze the expression of CD168 by immunohistochemistry
      in colorectal cancer (CRC) and to examine the association between CD168
      expression and clinicopathological features, including survival. A total of 78
      tissue specimens obtained from consecutive CRC patients exhibiting various tumor
      node metastasis (TNM) stages were immunostained for the analysis of CD168
      expression. The prognostic value of CD168 was subsequently evaluated. Kaplan
      Meier survival analysis revealed that CD168 overexpression was significantly
      associated with overall survival (P<0.05); however, no significant association
      was identified between CD168 expression and tumor location, tumor differentiation
      or TNM stage. Overexpression of CD168 was closely associated with poorer patient
      survival, which indicates that it may present a useful indicator for clinical
      prognosis.

PMID- 27698828
TI  - Autophagy inhibition augments resveratrol-induced apoptosis in Ishikawa
      endometrial cancer cells.
AB  - Resveratrol (RSV), a polyphenolic compound derived from red wine, inhibits the
      proliferation of various types of cancer. RSV induces apoptosis in cancer cells,
      while enhancing autophagy. Autophagy promotes cancer cell growth by driving
      cellular metabolism, which may counteract the effect of RSV. The present study
      aimed to elucidate the correlation between RSV and autophagy and to examine
      whether autophagy inhibition may enhance the antitumor effect of RSV in
      endometrial cancer cells. Cell proliferation, cell cycle progression and
      apoptosis were examined, following RSV exposure, by performing MTT assays, flow
      cytometry and annexin V staining, respectively, in an Ishikawa endometrial cancer
      cell line. Autophagy was evaluated by measuring the expression levels of light
      chain 3, II (LC3-II; an autophagy marker) by western blotting and
      immunofluorescence. Chloroquine (CQ) and small interfering RNAs targeting
      autophagy related (ATG) gene 5 (ATG5) or 7 (ATG7) were used to inhibit autophagy,
      and the effects in combination with RSV were assessed using MTT assays. RSV
      treatment suppressed cell proliferation in a dose-dependent manner in Ishikawa
      cells. In addition, RSV exposure increased the abundance of the sub-G1 population
      and induced apoptosis. LC3-II accumulation was observed following RSV treatment,
      indicating that RSV induced autophagy. Combination treatment with CQ and RSV more
      robustly suppressed growth inhibition and apoptosis, compared with RSV treatment
      alone. Knocking down ATG5 or ATG7 expression significantly augmented RSV-induced
      apoptosis. The results of the present study indicated that RSV-induced autophagy
      may counteract the antitumor effect of RSV in Ishikawa cells. Combination
      treatment with RSV and an autophagy inhibitor, such as CQ, may be an attractive
      therapeutic option for treating certain endometrial cancer cells.

PMID- 27698829
TI  - MicroRNA-486-5p enhances hepatocellular carcinoma tumor suppression through
      repression of IGF-1R and its downstream mTOR, STAT3 and c-Myc.
AB  - The insulin-like growth factor (IGF)-axis has been paradigmatically involved in
      hepatocellular carcinoma (HCC) tumor initiation, progression and drug resistance.
      Consequently, members of the IGF-axis and most importantly, IGF-1 receptor (IGF
      1R) have been considered as intriguing targets for HCC therapy. Few miRNAs have
      been recently reported to be associated with IGF-1R regulation. The present study
      aimed to investigate the role of microRNA (miRNA/miR)-486-5p in the regulation of
      IGF-1R and its downstream signaling cascades. miR-486-5p was markedly
      downregulated in hepatitis C virus-induced HCC tissues and Huh-7 cells. Forcing
      the expression of miR-486-5p in Huh-7 cells resulted in the repression of IGF-1R,
      mammalian target of rapamycin (mTOR), signal transducer and activator of
      transcription 3 (STAT3) and c-Myc mRNA levels. Ectopic expression of miR-486-5p
      in Huh-7 cells markedly repressed cellular viability, proliferation, migration
      and clonogenicity in a similar pattern to IGF-1R small interfering RNAs, and were
      evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,
      BrdU incorporation, wound healing and colony forming assays, respectively.
      Overall, the study findings demonstrated that miR-486-5p acts as a tumor
      suppressor in HCC through the repression of essential members of the IGF-axis,
      including IGF-1R and its downstream mediators mTOR, STAT3 and c-Myc.

PMID- 27698830
TI  - 17AAG-induced internalisation of HER2-specific Affibody molecules.
AB  - The geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) is
      known to induce internalisation and degradation of the otherwise internalisation
      resistant human epidermal growth factor receptor 2 (HER2) receptor. In the
      present study, 17-AAG was used to increase internalisation of the HER2-specific
      Affibody molecule ABY-025. The cellular redistribution of halogen-labelled 211At
      ABY-025 and radiometal-labelled 111In-ABY-025 following treatment with 17-AAG was
      studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human
      breast carcinoma cells to some extent shifted the localisation of 111In-ABY-025
      from the cell surface to intracellular compartments in the two cell lines. ABY
      025 labelled with the high-linear energy transfer alpha emitter 211At was also
      internalised to a higher degree; however, due to its physiological properties,
      this nuclide was excreted faster. The results indicate that 17-AAG may be used to
      facilitate cell-specific intracellular localisation of a suitable cytotoxic or
      radioactive agent coupled to ABY-025 in HER2-overexpressing cells.

PMID- 27698831
TI  - Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury
      caused by temozolomide.
AB  - Glioblastoma multiforme (GBM) is the most aggressive type of human primary brain
      tumor. The standard treatment protocol includes radiotherapy in combination with
      temozolomide (TMZ). Despite advances in GBM treatment, the survival time of
      patients diagnosed with glioma is 14.5 months. Regarding tumor biology, various
      types of cancer cell overexpress the ether a go-go 1 (Eag1) potassium channel.
      Therefore, the present study examined the role of Eag1 in the cell damage caused
      by TMZ on the U87MG glioblastoma cell line. Eag1 was inhibited using a channel
      blocker (astemizole) or silenced by a short-hairpin RNA expression vector
      (pKv10.1-3). pKv10.1-3 (0.2 ug) improved the Eag1 silencing caused by 250 uM TMZ,
      as determined by reverse transcription-quantitative polymerase chain reaction and
      immunocytochemistry. Additionally, inhibiting Eag1 with the vector or astemizole
      (5 uM) reduced glioblastoma cell viability and sensitized cells to TMZ. Cell
      viability decreased by 63% for pKv10.1-3 + TMZ compared with 34% for TMZ alone,
      and by 77% for astemizole + TMZ compared with 46% for TMZ alone, as determined by
      MTT assay. In addition, both the vector and astemizole increased the apoptosis
      rate of glioblastoma cells triggered by TMZ, as determined by an Annexin V
      apoptosis assay. Collectively, the current data reveal that Eag1 has a role in
      the damage caused to glioblastoma by TMZ. Furthermore, suppression of this
      channel can improve the action of TMZ on U87MG glioblastoma cells. Thus,
      silencing Eag1 is a promising strategy to improve GBM treatment and merits
      additional studies in animal models of glioma.

PMID- 27698832
TI  - Prognostic value of serum carbonic anhydrase IX in testicular germ cell tumor
      patients.
AB  - Despite the fact that testicular germ cell tumors (TGCTs) are one of the most
      chemosensitive solid tumors, a small proportion of patients fail to be cured
      following cisplatin-based first line chemotherapy. Upregulation of carbonic
      anhydrase IX (CA IX) in various solid tumors is associated with poor outcome. The
      current prospective study investigated the prognostic value of serum CA IX level
      in TGCTs. In total, 83 patients (16 non-metastatic following orchiectomy with no
      evidence of disease, 57 metastatic chemotherapy-naive and 10 metastatic relapsed
      chemotherapy-pretreated) starting adjuvant and/or new line of chemotherapy and 35
      healthy controls were enrolled in the study. Serum CA IX values were determined
      using an enzyme-linked immunosorbent assay, and intratumoral CA IX was analyzed
      by immunohistochemistry. Metastatic chemotherapy-naive patients had significantly
      higher mean CA IX serum levels than healthy controls (490.6 vs. 249.6 pg/ml,
      P=0.005), while there was no difference in serum CA IX levels in non-metastatic
      or relapsed TGCT patients compared with healthy controls. There was no
      significant difference in the mean serum CA IX levels between different groups of
      patients and between the first and second cycle of chemotherapy, nor association
      with patients/tumor characteristics. Serum CA IX was not prognostic for
      progression-free survival [hazard ratio (HR)=0.81, P=0.730] or overall survival
      (HR=0.64, P=0.480). However, there was a significant association between
      intratumoral CA IX expression and serum CA IX concentration (rho=0.51, P=0.040).
      These results suggest that serum CA IX level correlates with tumor CA IX
      expression in TGCT patients, but fails to exhibit either a prognostic value or an
      association with patients/tumor characteristics.

PMID- 27698833
TI  - Cisplatin-resistant osteosarcoma cells possess cancer stem cell properties in a
      mouse model.
AB  - Osteosarcoma is the most common malignancy of the bones, and although advances in
      chemotherapy and surgery had been achieved in recent years, the long-term
      survival rate has reached a plateau. The main reason for this is the aggressive
      malignant potential and poor response of the disease to chemotherapy. However,
      several studies have found that tumor resistance is associated with cancer stem
      cells (CSCs). To address this issue, in the present study, osteosarcoma cells
      were treated with specially designated concentrations of cisplatin (CDDP) in a
      mouse model. Hematoxylin and eosin staining analyses were performed to assess
      tissue structure, in vivo passaging and CDDP treatment. Drug resistance genes and
      well-established stemness genes were detected by quantitative polymerase chain
      reaction. A serum-starved sphere formation assay was adopted to evaluate the
      ability to generate spherical clones and flow cytometry as used to test the
      expression of the cluster of differentiation 117 and Stro-1 surface markers,
      known as markers of CSCs. It was found that CDDP could induce an effect of
      resistance in the osteosarcoma cells, which possessed cancer stem CSC properties,
      as shown by the elevated expression of CSC marker genes and the higher expression
      of the cluster of differentiation 117 and Stro-1 surface markers. Moreover, the
      cells that dissociated from the tumor tissues exhibited an increased ability to
      form sarcospheres. The results of this study provided a significant correlation
      between resistance and CSCs, and revealed a clue indicating that osteosarcoma
      recurrence is likely to be associated with CSCs.

PMID- 27698834
TI  - Decreased sirtuin 4 expression is associated with poor prognosis in patients with
      invasive breast cancer.
AB  - Aberrant metabolism is a hallmark of human cancer. Glutamine metabolism has been
      identified as a central metabolic pathway in cancer and thus, targeting glutamine
      metabolism may exhibit therapeutic potential. Sirtuin 4 (SIRT4) is an important
      molecule that mediates the blockade of glutamine catabolism by inhibiting
      glutamate dehydrogenase. In the present study, SIRT4 protein expression levels
      were analyzed in 409 breast cancer tissues and 241 paired adjacent non-cancerous
      tissues by immunohistochemical analysis and the correlation between SIRT4
      expression and the clinicopathological features was evaluated. SIRT4 protein was
      markedly increased in the breast cancer cells compared with adjacent non-tumor
      mammary cells and was correlated with estrogen receptor, progesterone receptor,
      nuclear-associated antigen Ki-67 and tumor protein p53 status, as well as breast
      cancer subtypes. Furthermore, low SIRT4 expression was associated with poor
      overall survival in breast cancers patients, particularly in Luminal A patients.
      Univariate and multivariate analyses confirmed that increased SIRT4 expression
      was an independent predictive factor of good prognosis for breast cancer
      patients. In conclusion, SIRT4 expression represents a significant favorable
      prognostic factor for patients with invasive breast cancer.

PMID- 27698835
TI  - Cerebellar hemangioblastoma mimicking an aneurysm: A case report and literature
      review.
AB  - Hemangioblastomas (HBMs) are highly vascular tumors of the central nervous
      system. Sporadic HBMs are nearly always solitary, and solitary HBMs are similar
      to intracranial arteriovenous malformations due to their highly vascular
      characteristics. However, to the best of our knowledge, cases of HBM in the
      cerebellum mimicking an aneurysm have never been reported in the literature. The
      present study reports a case of an HBM on the right cerebellar hemisphere
      mimicking an aneurysm, which originated from the right posterior inferior
      cerebellar artery, as determined using magnetic resonance angiography and digital
      subtraction angiography. The patient was admitted the Department of Neurosurgery
      at the Tsinghua University Yuquan Hospital (Beijing, China) in January 2015 due
      to a 4-year history of intermittent headaches. The diagnosis of an HBM was
      determined during surgery and the tumor was totally resected by changing the
      operation technique, with no complications. In conclusion, it is difficult to
      distinguish between HBMs and intracranial vascular diseases, particularly
      aneurysms. Surgeons should consider the possibility carefully prior to surgery
      and careful prepare for each eventuality.

PMID- 27698837
TI  - BCAT1 promotes tumor cell migration and invasion in hepatocellular carcinoma.
AB  - Branched-chain amino acid transaminase 1 (BCAT1) has been associated with
      numerous types of tumors; however, few previous studies have evaluated the
      expression and role of BCAT1 in hepatocellular carcinoma (HCC). In the present
      study, the expression of BCAT1 was detected by reverse transcription-quantitative
      polymerase chain reaction and immunoblotting in six HCC cell lines and 74 pairs
      of HCC and adjacent non-cancerous liver tissues. In addition, the correlation
      between the expression levels of c-Myc and BCAT1 was analyzed using
      immunohistochemistry. Furthermore, RNA silencing was performed using c-Myc
      specific or BCAT1-specific small interfering RNA, after which wound healing and
      Transwell cell invasion assays were performed. Finally, the clinicopathological
      characteristics of BCAT1 in patients with HCC were analyzed. It was shown that
      the expression of BCAT1 was significantly higher in HCC tissues compared with
      adjacent non-tumor tissues (P<0.001), and in HCC cell lines compared within the L
      02 hepatic cell line (P<0.001). In addition, immunohistochemical analyses
      indicated that the expression of BCAT1 was positively correlated with c-Myc
      (r=0.706, P<0.001). BCAT1 expression was shown to be downregulated in c-Myc
      knockdown cells, and silencing of BCAT1 expression reduced the invasion and
      migration of HCC cells. Furthermore, a clinical analysis indicated that BCAT1
      expression in HCC tissues was significantly associated with the tumor-node
      metastasis stage, tumor number and tumor differentiation (all P<0.05), and that
      BCAT1 was able to predict the 5-year survival and disease-free survival rates of
      patients with HCC (both P<0.001). The results of the present study suggested that
      BCAT1 expression is upregulated in patients with HCC, and that BCAT1 may serve as
      a potential molecular target for the diagnosis and treatment of HCC.

PMID- 27698836
TI  - Co-evolution of tumor-associated macrophages and tumor neo-vessels during
      cervical cancer invasion.
AB  - Considering the crucial significance of the tumor microenvironment in cancer
      development and progression, the present study aimed to investigate the changes
      in macrophages and angiogenesis during the cervical cancer (CC) progression
      process from chronic cervicitis to cervical intraepithelial neoplasia grades I
      III (CIN I-III) to CC. This investigation included quantitative analysis and
      assessment of the spatial associations between tumor-associated macrophages
      (TAMs) and tumor neo-vessels. The conventional immunohistochemistry staining
      technique was used to detect cluster of differentiation (CD)68 and CD105
      biomarker expression for TAMs and tumor neo-vessels, respectively. In addition,
      with the assistance of quantum dot (QD)-based two-component in situ imaging
      technology, the expression of the TAMs and tumor neo-vessels could be observed
      simultaneously. The quantitative analysis and co-evolution of the TAMs and tumor
      neo-vessels could then be processed. During the progression process from chronic
      cervicitis to cervical CIN I-III, and ultimately to invasive CC, the expression
      of the macrophages and neo-vessels in the tumor microenvironment increased
      synchronously. According to the quantitative analysis results, the median value
      of the TAM density was higher in the CC group (5,540.14) than in the CIN I-III
      group (2,502.17) and the chronic cervicitis group (1,403.31), with statistical
      significance in all three groups (P<0.001, for between-group comparisons). The
      number of neo-vessels was also much higher in the CC group (n=27) than in the CIN
      I-III group (n=17) or the chronic cervicitis group (n=6.5), with statistical
      significance in all three groups (P<0.001, for between-group comparisons). These
      findings demonstrated the great significance and close association of TAMs and
      tumor angiogenesis during CC development and progression. Thus, QDs-based in situ
      and simultaneous imaging of key cancer molecules may provide insights with regard
      to the biology of cancer invasion.

PMID- 27698838
TI  - Genetic analysis and clinical investigation of a pedigree with multiple endocrine
      neoplasia type 2A: A case report.
AB  - Multiple endocrine neoplasia 2A (MEN2A) is characterized by the coexistence of
      tumors that involve two or more endocrine glands within the same patient, and is
      defined as the occurrence of medullary thyroid carcinoma in association with
      pheochromocytoma (PHEO) and parathyroid tumors or hyperparathyroidism. The
      pathogenesis of MEN2A is due to the mutation of a tyrosine kinase receptor that
      is encoded by the rearrangement during transfection (RET) proto-oncogene. The
      mutation often occurs in exon 10q11.2. The present study reports the case of a 73
      year-old man with severe hypercalcemia, bilateral adrenal PHEO and a thyroid
      nodule. A genetic panel was obtained, and the RET mutation was indicated. The
      pedigree of the patient was also studied. Genetic testing of the patient's son
      indicated heterozygosity for the same mutation at codon 634. The first symptom of
      the two patients was PHEO, which is uncommon. In addition, varied phenotypes were
      identified in the two patients. In the present study, the association between the
      phenotypic variation of the RET gene and the occurrence of MEN2A is discussed.

PMID- 27698839
TI  - Perioperative stroke in a patient undergoing surgery for oral cancer: A case
      report.
AB  - Carotid artery stenosis is a significant risk factor for stroke. In elderly
      patients with carotid atherosclerosis and stenosis, it is not unusual for oral,
      head and neck cancer surgery to be performed. The present study describes a case
      of stroke that occurred during a neck dissection for the treatment of cervical
      lymph node metastasis of a left maxillary gingival carcinoma. The patient was an
      84-year-old female who was considered to be at high risk of a stroke based on pre
      operative head and neck computed tomography scans, which detected severe carotid
      atherosclerosis and stenosis. There was no possible stroke prophylaxis available
      during the performance of the neck dissection in the present case. However, if
      patients are evaluated to be high-risk pre-operatively, statin agents should be
      administered, the surgery should be carefully performed, adequate sedation should
      be maintained post-operatively and the patient should be followed up, aiming to
      achieve the early detection of a possible stroke.

PMID- 27698840
TI  - Association between FOXM1 and hedgehog signaling pathway in human cervical
      carcinoma by tissue microarray analysis.
AB  - Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the
      formation and development of human tumors, including cervical cancer. Previous
      studies have indicated that FOXM1 may be a downstream target gene of the Hh
      signaling pathway, but their association in cervical cancer is largely unknown.
      In the present study, the expression of FOXM1 and Hh signaling molecules was
      evaluated by immunohistochemical analysis in a tissue microarray that contained
      70 cervical cancer tissues and 10 normal cervical tissues. In addition, the
      association of these molecules with clinicopathological parameters, and the
      association between FOXM1 and various molecules involved in the Hh signaling
      pathway was investigated. The results indicated that FOXM1 and Hh signaling
      molecules were overexpressed in cervical cancer tissues. The protein expression
      levels of FOXM1, glioma-associated oncogene 1 (GLI1) and smoothened (SMO)
      correlated with the clinical stage of the tumors, while the protein expression
      levels of Sonic Hh (SHh), patched 1 (PTCH1) and GLI1 correlated with the
      pathological grade of the tumors. The expression levels of GLI1 were lower in
      tissues without lymph node metastasis than in tissues with lymph node metastasis.
      In addition, FOXM1 expression correlated with GLI1, SHh and PTCH1 expression in
      cancer tissues. These findings confirmed the participation of FOXM1 and the Hh
      signaling pathway in cervical cancer. Furthermore, the finding that FOXM1 may be
      a downstream target gene of the Hh signaling pathway in cervical cancer provides
      a potential novel diagnostic and therapeutic target for cervical cancer.

PMID- 27698842
TI  - Tazarotene-induced gene 2 is associated with poor survival in non-small cell lung
      cancer.
AB  - The aim of the present study was to investigate the expression of tazarotene
      induced gene 2 (TIG2) and evaluate the clinicopathological variables and
      prognostic value for non-small cell lung cancer (NSCLC) patients. Reverse
      transcription-polymerase chain reaction and western blotting were utilized to
      detect TIG2 expression in NSCLC specimens and adjacent noncancerous tissue.
      Furthermore, the present study investigated the protein expression and the
      clinicopathological significance of TIG2 in 98 paraffin-embedded NSCLC samples by
      using immunohistochemistry. The results of the present study demonstrated that
      the expression of TIG2 mRNA (P=0.003) and protein (P=0.0024) was significantly
      reduced in NSCLC compared with corresponding noncancerous tissue. TIG2 protein
      expression in NSCLC was significantly associated with lymph node metastasis
      (P=0.006), Tumor-Node-Metastasis stage (P=0.021) and degree of differentiation
      (P=0.025). The Kaplan-Meier method and log-rank test revealed that high TIG2
      expression was significantly associated with increased survival of NSCLC patients
      (P=0.003). Multivariate analysis revealed that TIG2 expression was an independent
      prognostic factor of the overall survival of NSCLC patients. Decreased expression
      of TIG2 may be useful as a biomarker for poor prognosis in NSCLC carcinogenesis
      and may act as a target for gene therapy for the treatment of NSCLC patients.

PMID- 27698841
TI  - SPAG9 is overexpressed in osteosarcoma, and regulates cell proliferation and
      invasion through regulation of JunD.
AB  - Sperm-associated antigen 9 (SPAG9) is a recently characterized oncoprotein that
      is considered to be involved in several forms of malignant tumor. However, its
      biological function and expression pattern in human osteosarcoma have not yet
      been elucidated. In the present study, SPAG9 expression was analyzed in 58 cases
      of human osteosarcoma by immunohistochemistry. The results demonstrated that
      SPAG9 was overexpressed in 63.8% (37/58) of osteosarcoma tissues, while normal
      bone tissues exhibited negative SPAG9 expression. SPAG9 small interfering RNA was
      employed in the U2OS cell line, which has high endogenous expression, and SPAG9
      transfection was performed in the MG63 cell line, which has low endogenous
      expression. MTT and Matrigel invasion assays demonstrated that SPAG-9-knockdown
      significantly reduced U2OS cell invasion and proliferation, while SPAG9
      transfection enhanced MG63 cell proliferation and invasion. Furthermore, it was
      observed that SPAG9 positively regulated cyclin D1, phosphorylated-c-Jun NH2
      terminal kinase (JNK) and JunD expression. Treatment with the JNK inhibitor,
      SP600125, abolished the upregulatory effect of SPAG9 on JunD. Taken together, the
      present study identified SPAG9 as a critical oncoprotein involved in osteosarcoma
      proliferation and invasion, possibly functioning through JNK-JunD signaling.

PMID- 27698843
TI  - Functional redundancy of the Notch pathway in ovarian cancer cell lines.
AB  - Epithelial ovarian cancer is the most lethal gynecologic malignancy, despite
      advances in treatment. The most common histological type, high-grade ovarian
      serous carcinoma (OSC) is usually diagnosed at an advanced stage, and although
      these types of tumors frequently respond to surgery and platinum-based
      chemotherapy, they usually recur. Ovarian clear cell carcinoma (OCCC) is an
      unusual histological type, which is known to be intrinsically chemoresistant and
      is associated with poor prognosis in advanced stages. In recent years, genetic
      alterations and epigenetic modulation of signaling pathways have been reported in
      OSC and OCCC, including the overexpression of Notch pathway elements and histone
      deacetylases. Histone deacetylase inhibitors (HDACis), including vorinostat
      (suberoylanilide hydroxamic acid), alter the transcription of genes involved in
      cell growth, survival and apoptosis, and have become an attractive therapeutic
      approach. However, no previous work has addressed the effect of HDACis, and in
      particular vorinostat, on Notch signaling in ovarian cancer. Therefore, the
      present study aimed to investigate the modulation of the Notch pathway by
      vorinostat in ovarian cancer. Using immunofluorescence and quantitative
      polymerase chain reaction, the present results revealed that vorinostat activated
      the Notch pathway in OCCC and OSC cell lines, through different Notch ligands. In
      OCCC, the activation of the Notch pathway appeared to occur through Delta-like
      (Dll) ligands 1, 2 and 3, whereas in OSC Dll1 and Jagged 1 and 2 ligands were
      involved. The activation of the Notch pathway by vorinostat, in OCCC and OSC cell
      lines, culminated in the increased expression of the same downstream
      transcription factors, hairy enhancer of split (Hes) 1 and 5, and Hes-related
      proteins 1 and 2. In conclusion, vorinostat modulates the expression of several
      downstream targets of the Notch pathway and independent Notch receptors and
      ligands that are expressed in OSC and OCCC. This upregulation of the Notch
      pathway may explain why vorinostat therapy fails in ovarian carcinoma treatment,
      as shown in certain clinical trials.

PMID- 27698844
TI  - Primitive neuroectodermal tumor originating from the lung: A case report.
AB  - Primitive neuroectodermal tumors (PNETs) are small, round cell tumors that may be
      classified as peripheral or central, based on their site of origin. PNETs often
      arise in the soft tissue or bone of young adults. Although not common, PNETs have
      been described in other organs, including the gonads, kidneys, myocardium and
      pancreas, but rarely in the lungs without chest wall or pleural involvement. The
      present study reports a rare case of peripheral PNET (pPNET), which originated in
      the lung. A 37-year-old female patient presented at Xuzhou Central Hospital
      (Xuzhou, China) with a history of a dry cough, mild dyspnea and slight pain in
      the left chest. Histopathological and immunohistochemical analyses permitted the
      diagnosis of a pPNET. The patient was treated with surgical resection, followed
      by chemotherapy (including cyclophosphamide, cisplatin and vincristine),
      radiotherapy and traditional Chinese medicine (including Kanglaite and Shenqi
      Fuzheng injections). At the time of writing, the patient was alive with no sign
      of recurrence and under regular follow-ups at the Outpatient Clinic of Xuzhou
      Central Hospital.

PMID- 27698845
TI  - Multidisciplinary collaboration in gallbladder carcinoma treatment: A case report
      and literature review.
AB  - Gallbladder carcinoma (GBC) is a rare and highly aggressive disease. The
      diagnosis of this cancer is difficult due to its occult onset. Hence, GBC is
      often detected late and at an advanced stage. Although physicians and researchers
      are continually working to improve the treatment for advanced-stage disease, GBC
      is usually associated with short survival times. The present study describes a
      case of GBC that was first diagnosed with accompanying cholecystolithiasis at the
      time of cholecystectomy. Cancer relapse occurred 1.5 years after the
      cholecystectomy. Multidisciplinary collaboration was involved in the decision
      making process for the treatment of this aggressive recurrence, and the survival
      time was successfully extended to 26 months. Importantly, high-grade
      intraepithelial neoplasia and positive margins had previously been detected post
      cholecystectomy at a different institution, but were ignored. Relapse may have
      been preventable had the cancer been diagnosed when it was initially observed.
      Taken together, these findings suggest that multidisciplinary collaboration
      should be considered for the management of advanced GBC, whereby patients will
      benefit from improved survival times. Furthermore, it is recommended that samples
      obtained from patients undergoing cholecystectomy should more carefully analyzed
      for evidence of cancerous or precancerous tissues.

PMID- 27698846
TI  - Expression of early growth response gene-1 in precancerous lesions of gastric
      cancer.
AB  - Several studies have demonstrated a correlation between the expression of early
      growth response gene-1 (EGR-1) and the progression of gastric cancers at advanced
      stages. However, the effects of EGR-1 expression on human gastric cancer
      progression, particularly on precancerous lesions, have not been investigated. In
      this study, we evaluate EGR-1 expression levels in target mucosa from patients
      with early gastric cancer and precancerous lesions, and assess whether EGR-1
      expression affects the oncogenic phenotypes of human gastric cancer cells. EGR-1
      protein levels were measured in tissues from subjects with normal mucosa (n=6),
      low-grade dysplasia (n=6), high-grade dysplasia (n=4) and adenocarcinoma (n=3)
      using enzyme-linked immunosorbent assay and immunohistochemistry analyses. We
      also investigated the role of EGR-1 in tumor cell behavior by transiently
      expressing a dominant active EGR-1 variant in cultured cells. A positive
      correlation was observed between EGR-1 expression and gastric carcinogenesis
      (P=0.016). Furthermore, there was an increase in nuclear and cytoplasmic
      expression of EGR-1 in accordance with the histological grade (P for trends=0.003
      and 0.003, respectively), and a positive association between the sum of the
      nuclear and cytoplasmic EGR-1 expression values and the histological grade
      (P=0.003). In addition, transient overexpression of EGR-1 enhanced cell
      proliferation, stimulated cell migration, and promoted the phosphorylation of p38
      MAPK and AKT in gastric cancer cells in vitro. Our findings demonstrate that EGR
      1 may contribute to the early stages of gastric carcinogenesis via the alteration
      of tumor cell behaviors.

PMID- 27698847
TI  - Paraneoplastic Morvan's syndrome following surgical treatment of recurrent
      thymoma: A case report.
AB  - Morvan's syndrome (MoS) is a rare, complex neurological disorder characterized by
      neuromyotonia, neuropsychiatric features, dysautonomia and neuropathic pain. The
      majority of MoS cases have a paraneoplastic aetiology, usually occurring prior to
      the diagnosis of the underlying tumour and showing improvement following its
      treatment. The present study reports the case of a 35-year-old Caucasian male
      patient who was diagnosed with stage IVA thymoma. Thymectomy, lung resection,
      diaphragmatic pleurectomy and pericardio-phrenectomy were performed 6 months
      after neoadjuvant chemotherapy. The pathological evaluation revealed a type B2-B3
      thymoma with focal squamous differentiation. Two years later, the patient
      underwent new surgical treatment for a local recurrence of the same histological
      type, and 4 weeks later, the patient presented with complex neurological symptoms
      compatible with MoS, including neuromyotonia, neuropsychiatric features,
      dysautonomia and neuropathic pain. Electromyography was compatible with a
      diagnosis of neuromyotonia. Brain magnetic resonance imaging scan and tests for
      serum anti-acetylcholine receptor, anti-striated muscle antibodies and anti-30
      kDa titin fragment antibodies were all negative, whereas tests for anti-voltage
      gated potassium channel (VGKC)-complex antibodies (333.3 pmol/l), anti-leucine
      rich glioma inactivated protein 1 and anti-contactin-associated protein-like 2
      antibodies were positive. The patient underwent 3 cycles of intravenous
      administration of immunoglobulins (0.4 g/kg/day for 5 days every 4 weeks) with
      little clinical and electrophysiological improvement. We speculated that the late
      onset of the symptoms in the present patient may have been triggered by an
      increase in the serum level of anti-VGKC antibody, which was caused by the
      surgery performed for the treatment of recurrent thymoma. To the best of our
      knowledge, the present report is the first case of MoS associated with this
      histological type of thymoma uncommonly occurring upon surgical treatment of
      recurrent thymoma.

PMID- 27698848
TI  - Clinicopathological analysis of CD44 and CD24 expression in invasive breast
      cancer.
AB  - A subpopulation of breast cancer cells with cluster of differentiation (CD)44
      positive and CD24-negative expression has been reported to have stem cell
      properties and to have a higher tumorigenic capacity than other cells. However,
      the clinicopathological characteristics of this subpopulation are not fully
      understood. In this study, we aimed to identify the correlations between the
      expression of CD44 and CD24 and clinicopathological parameters and overall
      survival. We studied specimens from 262 patients with invasive breast cancer.
      Immunohistochemical staining for CD44 and CD24 was performed using tissue
      microarrays. The clinicopathological factors were evaluated from the patients'
      medical records. In correlation analysis, CD44 expression was significantly
      associated with human epidermal growth factor receptor 2 (HER2)-negative status
      (P<0.001). Conversely, CD24 expression was significantly associated with HER2
      positive status (P<0.001). CD44 and CD24 expression did not demonstrate any
      correlation with the age, tumor size, axillary lymph node metastasis status,
      tumor stage, histological grade, estrogen receptor status and progesterone
      receptor status of patients. Upon survival analysis, there was no statistical
      difference in overall survival according to the expression of CD44 and CD24. The
      results from this study suggest that CD44 and CD24 are clinically significant
      markers associated with breast tumorigenesis, but not sufficient factors in
      determining the prognosis of invasive breast cancer.

PMID- 27698849
TI  - Fluorescence in situ hybridization testing of chromosomes 6, 8, 9 and 11 in
      melanocytic tumors is difficult to automate and reveals tumor heterogeneity in
      melanomas.
AB  - Malignant melanomas may be difficult to differentiate from benign nevi on the
      basis of histology. Contrary to nevi, the majority of melanomas harbor
      chromosomal imbalances. Comparative genomic hybridization-based and fluorescence
      in situ hybridization (FISH) tests can help differentiating malignant from benign
      tumors. In the present study, eight-bacterial artificial chromosome (BAC) probes
      targeting chromosomes 6, 8, 9 and 11 were tested by FISH, and compared with a
      commercial four-color FISH probe set targeting chromosomes 6 and 11 in a first
      set of 62 tissue microarray-included melanocytic tumors (47 melanomas and 15
      nevi). A second set of 108 tumors (70 melanomas and 38 nevi) was analyzed with
      the eight-probes kit, and manual counting was compared with the newly developed
      automated FISH signals counting and with semi-quantitative visual detection of
      chromosomal imbalances. Intra-tumor heterogeneity was also evaluated in 12
      melanomas and 10 patients with paired melanoma samples. Testing the tumors from
      the first set with the commercial kit and the eight-probes test permitted to
      correctly identify 45/47 and 47/47 melanomas, respectively. In the second tumor
      set, 65/70 malignant tumors presented at least one chromosomal imbalance, whereas
      none was detected in the nevi. The agreement between manual and automated signals
      counting was better in good-quality FISH slides compared with poor-quality
      slides. Semi-quantitative visual appreciation of chromosomal imbalances also
      reached strong agreement with exact manual counting. In addition, a frequent
      cytogenetic heterogeneity within melanomas and between paired tumors was noticed
      in patients with metastatic melanomas. To conclude, FISH testing targeting
      chromosomes 6, 8, 9 and 11 enabled to differentiate the majority of melanomas
      from nevi but was difficult to automate. Tumor cytogenetic heterogeneity was
      frequent and could impair FISH testing.

PMID- 27698850
TI  - Killian-Jamieson diverticulum mimicking a calcified thyroid nodule on
      ultrasonography: A case report and literature review.
AB  - As a rare hypopharyngeal diverticulum, Killian-Jamieson diverticulum (KJD) is
      usually incidentally detected, small, asymptomatic and likely to be misdiagnosed
      as a thyroid nodule. In order to avoid unnecessary treatments resulting from
      misdiagnosis, principles to distinguish between esophageal diverticula and
      thyroid nodules should be noted clearly. The current study presents a case of an
      asymptomatic unilateral KJD that mimicked a calcified thyroid nodule. In the
      current case, a 40-year-old man presented with a 'suspected malignant thyroid
      nodule' in the left thyroid gland, and underwent left thyroid lobectomy and a
      neck exploration. However, no visible 'suspected tumor', but a sac protruding
      from the left anterolateral wall of the cervical esophagus, was observed during
      the surgery. A swallow test on ultrasonography (US) in combination with
      pharyngoesophagography was then performed, which confirmed the diagnosis. The
      patient recovered well during the 3-month follow-up after the operation. The
      present study indicates that real-time US and pharyngoesophagography are
      important techniques to distinguish a KJD from a thyroid nodule so that
      unnecessary surgical intervention can be avoided.

PMID- 27698851
TI  - Novel dynamin 2 mutations in adult T-cell acute lymphoblastic leukemia.
AB  - Genetic mutations on signaling pathways are found in patients with T-cell acute
      lymphoblastic leukemia (T-ALL) and act as markers of high-risk leukemia.
      Mutations in dynamin 2 (DNM2) have been reported in T-ALL, particularly in early
      T-cell precursor-ALL. In the present study, DNM2 mutations were screened by
      sequencing DNM2 exons obtained by polymerase chain reaction amplification and gel
      purification in adult T-ALL patients. A total of 4 novel DNM2 mutations were
      identified in adult T-ALL patients, with a mutation rate of 9.5%, and the DNM2
      mutations were found to co-exist with NOTCH1 and PHD finger protein 6, and were
      also associated with high-risk leukemia. A high rate of silent mutation was also
      found in the patients, but no significant association was found between the
      silent mutations and patients' clinical features. The present findings suggested
      the DNM2 mutations may be involved in the oncogenesis of T-ALL.

PMID- 27698852
TI  - ABCG2 expression in colorectal adenocarcinomas may predict resistance to
      irinotecan.
AB  - Irinotecan is a key drug for patients with advanced and recurrent colorectal
      carcinoma. However, the efficacy of irinotecan is not sufficient; partly, as
      there is no useful marker to predict chemosensitivity to the drug. The aim of the
      present study was to evaluate whether the expression levels of adenosine
      triphosphate-binding cassette sub-family G (WHITE) member 2 (Junior blood group)
      (ABCG2) in primary colorectal tumors predict chemoresistance to irinotecan. Using
      the resected primary tumor specimens of 189 patients with colorectal cancer, the
      association between the immunohistochemical expression of ABCG2 protein and the
      results of the collagen gel droplet embedded culture drug sensitivity test,
      performed to evaluate the chemosensitivity to SN-38 (an active metabolite of
      irinotecan), was investigated. Among the 189 patients, 17 received irinotecan
      based chemotherapy, and their responses and progression-free survival (PFS) were
      analyzed. The tumors of patients with increased ABCG2 expression accounted for
      60% of the tumors examined, and were significantly more resistant to SN-38,
      compared with patients with low ABCG2 expression (P<0.001). In a multivariate
      logistic regression analysis, increased expression of ABCG2 protein was an
      independent and significant predictor of resistance to SN-38, increasing the risk
      of resistance by 12-fold. Increased expression of ABCG2 and a low sensitivity to
      SN-38 was significantly associated with resistance to irinotecan-based
      chemotherapy (P=0.01 and 0.028, respectively). The median PFS of patients with
      increased expression of ABCG2 was significantly shorter, compared with patients
      with low expression levels of ABCG2 (104 vs. 242 days; P=0.047). The increased
      immunohistochemical expression of ABCG2 in primary tumors may be a useful
      predictive biomarker of resistance to irinotecan-based chemotherapy for patients
      with recurrent or metastatic colorectal cancer.

PMID- 27698853
TI  - Deguelin inhibits proliferation and migration of human pancreatic cancer cells in
      vitro targeting hedgehog pathway.
AB  - Pancreatic cancer (PC) is a highly lethal malignancy with few effective
      therapies. Deguelin, a natural compound of the flavonoid family of products, has
      been reported to have an inhibitory effect on various cancers. In the present
      study, we investigated whether deguelin had antitumor efficacy in PC. Deguelin
      treatment was observed to inhibit growth and induce apoptosis in two PC cell
      lines (Bxpc-3 and Panc-1). In addition, it inhibited migration and invasion in
      these two cell lines. The activation of the hedgehog (Hh) signaling pathway, as
      well as matrix metalloproteinases (MMP)-2 and MMP-9, was suppressed by deguelin.
      These results suggest that deguelin may be a potential chemotherapeutic agent for
      PC, possibly through the suppression of the Hh signaling pathway.

PMID- 27698854
TI  - Misdiagnosed infantile rhabdomyofibrosarcoma: A case report.
AB  - Infantile rhabdomyofibrosarcoma is a rare form of soft-tissue tumor often
      associated with difficulties in diagnosis. The disease is positioned
      intermediately between rhabdomyosarcoma and infantile fibrosarcoma in terms of
      clinical presentation, immunohistochemistry, behavior, morphology and
      ultrastructural features. Reports of rhabdomyofibrosarcoma cases are limited in
      the literature. The present case describes a 26-month-old female who presented
      with a slowly progressive, soft-tissue mass in the right chest wall. The mass was
      successfully treated with surgery. Using histopathology, the tumor was diagnosed
      and classified as infantile rhabdomyofibrosarcoma. The patient has been followed
      up for 2 years and is currently in good condition. The present case demonstrates
      that early, radical, local surgery and multidisciplinary cooperation were
      successful for the treatment of rhabdomyofibrosarcoma, and close follow-up highly
      recommended.

PMID- 27698855
TI  - Aneurysmal bone cyst of the metatarsal: A case report.
AB  - An aneurysmal bone cyst (ABC) is a rare, non-neoplastic, destructive, hemorrhagic
      and expansile lesion accounting for 1% of all bone tumors. This type of lesion
      predominantly affects long bones and vertebrae. ABC of the metatarsal is rare and
      only a few cases have been reported in the literature to date. The present study
      reports a rare case of ABC of the third metatarsal occurring in a 27-year-old
      male patient, who presented with repeated foot swelling that had lasted for ~1
      year. Other clinical manifestations included limping, multiple lumps (defined as
      masses on or below the skin, as detected by imageological diagnosis) and
      progressively increasing local pain in his right foot. Magnetic resonance imaging
      of the right metatarsal revealed a segmented, expansile, multiseptated lesion
      with fluid-fluid levels. An en bloc resection was performed and the defect was
      replaced with a tricortical iliac autograft. Pathological analysis of the
      resected tissue suggested ABC. The present study aims to describe a case of ABC
      of the metatarsal, a condition that often poses a diagnostic challenge, and to
      underline the importance of radiological and histological examinations for the
      accuracy of that diagnosis.

PMID- 27698856
TI  - Primary gastrointestinal stromal tumor of the liver: A case report and review of
      the literature.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors
      located in the alimentary tract. A small portion of GISTs are observed in extra
      gastrointestinal regions, primarily in the omentum, mesentery and retroperioneum,
      and these types of GISTs are referred to as extra-gastrointestinal stromal
      tumors. The present study reports of a patient with unique primary liver GIST.
      The patient underwent en bloc resection and post-operative administration of
      imatinib, and subsequently experienced a good prognosis. The present case is
      followed by a brief review of reported cases of liver GISTs identified in the
      literature. The literature revealed that primary liver GISTs are usually large in
      size and possess a high mitotic index, which contributes to malignant
      characterization, thus classifying these tumors as high-risk. En bloc resection
      remains the mainstay of treatment for resectable primary liver GISTs. However,
      the prognosis of these patients is not favorable. Perioperative administration of
      imatinib may be useful to a certain extent, and interventional therapy, including
      radiofrequency ablation, should be considered.

PMID- 27698857
TI  - Immunohistochemical patterns in the differential diagnosis of rhinopharyngeal
      granulocytic sarcoma.
AB  - Granulocytic sarcoma (GS) is a rare extramedullary manifestation of acute myeloid
      leukemia (AML). GS may develop simultaneously to AML or as a relapse of leukemia,
      particularly following allogeneic hematopoietic stem cell transplant.
      Subperiosteal bone, lymph nodes and skin are commonly involved, whereas
      rhinopharyngeal involvement is less common, with only 14 cases reported in the
      literature. Due to its rarity, rhinopharyngeal GS may lead to diagnostic
      pitfalls, particularly when it is poorly differentiated or is without concomitant
      marrow involvement. Thus, immunohistochemical findings play a key role in
      diagnosis. The current report describes a case of a 53-year-old female suffering
      from rhinopharyngeal GS and with a history of AML treated with chemotherapy and
      radiotherapy, focusing on the importance of the immunohistochemical pattern to
      assess the right diagnosis. Recent studies have demonstrated that the
      immunophenotype is of utmost importance for the diagnosis of GS. The high
      expression of myeloperoxidase (MPO) is common in GS; however, ~30% of GSs do not
      contain MPO. Therefore, the presence of other markers is required to confirm the
      diagnosis of GS.

PMID- 27698859
TI  - Iodine-125 irradiation inhibits invasion of gastric cancer cells by reactivating
      microRNA-181c expression.
AB  - Iodine-125 (125I) seed implantation has been widely used for the treatment of
      unresectable advanced tumors. However, the molecular mechanisms underlying the
      tumor-suppressive effects of 125I irradiation have not been fully elucidated. The
      present study demonstrated that 125I irradiation suppresses cell viability and
      inhibits cell invasiveness of gastric cancer KATO-III and MKN45 cells. Further
      mechanistic analysis suggested the involvement of microRNA (miR)-181c in the
      inhibitory effects induced by 125I irradiation. Methylated DNA
      immunoprecipitation coupled with quantitative-polymerase chain reaction
      demonstrated that treatment with 125I irradiation, at the dose of 4 Gy, induced
      promoter demethylation of the miR-181c gene in KATO-III and MKN45 cells.
      Following irradiation, the expression of miR-181c was significantly increased,
      which may be attributed to the demethylation caused by 125I irradiation. In
      addition, upregulation of miR-181c by administration of miR-181c mimics decreased
      cell invasion, suggesting the role of miR-181c as a tumor suppressor. More
      importantly, the tumor-suppressive effects of 125I irradiation were significantly
      compromised by the introduction of miR-181c inhibitors. Overall, these results
      reveal that 125I irradiation inhibits invasiveness of gastric cancer cells by
      reactivating miR-181c at the epigenetic level, thereby providing important
      molecular evidence for the anticancer effects of 125I irradiation.

PMID- 27698860
TI  - Leucine zipper, down regulated in cancer-1 gene expression in prostate cancer.
AB  - Numerous genetic alterations have been implicated in the development of prostate
      cancer (PCa). DNA and protein microarrays have enabled the identification of
      genes associated with apoptosis, which is important in PCa development. Despite
      the molecular mechanisms are not entirely understood, inhibition of apoptosis is
      a critical pathophysiological factor that contributes to the onset and
      progression of PCa. Leucine zipper, down-regulated in cancer 1 (LDOC-1) is a
      known regulator of the nuclear factor (NF)-mediated pathway of apoptosis through
      the inhibition of NF-kappaB. The present study investigated the expression of the
      LDOC-1 gene in LNCaP, PC-3, PNT1A and PNT2 prostate cell lines by reverse
      transcription-quantitative polymerase chain reaction. In addition LDOC-1 protein
      expression in normal prostate tissues and PCa was studied by
      immunohistochemistry. LDOC-1 messenger RNA resulted overexpressed in LNCaP and PC
      3 PCa cell lines compared with the two normal prostate cell lines PNT1A and PNT2.
      The results of immunohistochemistry demonstrated a positive cytoplasmic LDOC-1
      staining in all PCa and normal prostate samples, whereas no nuclear staining was
      observed in any sample. Furthermore, a more intense signal was evidenced in PCa
      samples. LDOC-1 gene overexpression in PCa suggests an activity of LDOC-1 in PCa
      cell lines.

PMID- 27698861
TI  - IgM multiple myeloma with an extremely rare non-aggressive presentation: A case
      report.
AB  - In the present study, the case of a 41-year-old man with immunoglobulin (Ig)M
      multiple myeloma (MM) that presented with an unusually non-aggressive clinical
      course who has survived for >9 years to date, is presented. Initial diagnosis of
      symptomatic MM was established according to the International Myeloma Working
      Group consensus statement and guidelines. Due to the mild symptoms, no therapy
      was administered and the patient was closely followed up. Eight years after
      initial diagnosis, clinical, morphological and genetic progression occurred with
      the development of hypercalcemia, progressively deteriorating polyneuropathy,
      clonal expansion of plasma cells up to 50% of hematopoietic cells and
      demonstration of the typical t(11;14) translocation (Ig heavy chain locus
      rearrangement). Subsequently, 4 cycles of induction chemotherapy with velcade,
      cyclophosphamide and dexamethasone, were administered. At the time of writing,
      the patient remained alive in generally good health. To the best of our
      knowledge, with a survival time of >9 years, this case reports the longest
      survival time of an IgM MM patient to date, which contradicts previous evidence
      that suggests IgM MM exhibits an aggressive clinical course.

PMID- 27698858
TI  - Differential expression of viral agents in lymphoma tissues of patients with ABC
      diffuse large B-cell lymphoma from high and low endemic infectious disease
      regions.
AB  - Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's
      lymphoma (NHL) in adults, accounts for approximately 30-40% of newly diagnosed
      lymphomas worldwide. Environmental factors, such as viruses and bacteria, may
      contribute to cancer development through chronic inflammation and the integration
      of oncogenes, and have previously been indicated in cervical cancer,
      hepatocellular carcinoma, gastric cancer and lymphoproliferative disorders. In
      the present study, the presence of microbial agents was analyzed in the lymphoma
      tissue of patients with activated B-cell like (ABC) DLBCL. The present study
      compared two groups of patients from geographically varied regions that possess a
      difference in the prevalence of viral and other microbial agents. The patient
      populations were from Sweden (a low endemic infectious disease region) and Egypt
      (a high endemic infectious disease region). A differential expression of several
      viruses in lymphoma tissues was noted when comparing Swedish and Egyptian
      patients. JC polyomavirus (JCV) was detected in Swedish and Egyptian patients
      and, uniquely, the complete hepatitis B virus (HBV) genome was detected only in
      Egyptian lymphoma patients. None of these viruses were detected in control lymph
      tissues from Sweden or Egypt. In total, 38% of the Egyptian patients were found
      to have HBV surface antigens (HBsAgs) in their serum; however, HBsAgs were not
      found in any of the Swedish patients. The percentage of serum HBsAgs in Egyptian
      patients with ABC DLBCL was significantly increased compared with the general
      Egyptian population (P<0.05). The present study may support a notion that viral
      agents, including JCV and HBV, may be involved in the tumorigenesis of DLBCL in
      regions of high infectious disease.

PMID- 27698862
TI  - Aspirin may inhibit angiogenesis and induce autophagy by inhibiting mTOR
      signaling pathway in murine hepatocarcinoma and sarcoma models.
AB  - Aspirin is known to have inhibitory effects on growth development in various
      types of tumor. In previous studies, it was observed to inhibit angiogenesis by
      downregulating the expression of vascular endothelial growth factor-A (VEGF-A).
      In the present study, murine H22 hepatocarcinoma and S180 sarcoma models were
      used to ascertain whether aspirin could inhibit angiogenesis and promote
      autophagy in tumors. Tumor-bearing mice were randomly divided into four groups
      with 10 mice per group: i) no treatment; ii) low-dose aspirin (100 mg/kg); iii)
      high-dose aspirin (400 mg/kg); iv) everolimus group (4 mg/kg). The effects of
      high-dose aspirin were validated through preliminary experiments. The drug
      treatment was administered every day for 14 days. The tumor size was measured
      every other day and then the tumor growth curve was plotted, and the tumor
      inhibitory rates were calculated. The expression levels of phosphorylated
      mammalian target of rapamycin (p-mTOR), hypoxia-inducible factor-1alpha (HIF
      1alpha), VEGF-A, UNC-51-like kinase-1 (ULK1) and microtubule-associated protein 1
      light chain 3A (LC3A) were detected by immunohistochemistry and western blot
      analysis, respectively. We observed that tumor growth delay was achieved in both
      H22 hepatocarcinoma and S180 sarcoma models following treatment with aspirin. The
      tumor growth inhibition rates induced by low and high-dose aspirin and everolimus
      were 19.6, 33.6 and 53.7% (P<0.05) in H22 hepatocarcinoma, and 25.7, 40.6 and
      48.7% (P<0.05) in S180 sarcoma. The immunohistochemistry and western blot
      analysis data from the models revealed that the expression of p-mTOR, HIF-1alpha
      and VEGF-A was decreased, while the expression of ULK1 and LC3A was increased
      following treatment with aspirin and everolimus. The changes were more apparent
      in the high-dose aspirin and everolimus groups (P<0.01). The inhibitory action of
      aspirin and everolimus on tumor angiogenesis may be through inhibiting the
      expression of p-mTOR, HIF-1alpha and VEGF-A. Alternatively, aspirin may induce
      autophagy by inhibiting the mTOR signaling target and then increasing ULK1 and
      LC3A.

PMID- 27698863
TI  - Promoter methylation and downregulated expression of the TBX15 gene in ovarian
      carcinoma.
AB  - TBX15 is a gene involved in the development of mesodermal derivatives. As the
      ovaries and the female reproductive system are of mesodermal origin, the aim of
      the present study was to determine the methylation status of the TBX15 gene
      promoter and the expression levels of TBX15 in ovarian carcinoma, which is the
      most lethal and aggressive type of gynecological tumor, in order to determine the
      role of TBX15 in the pathogenesis of ovarian carcinoma. This alteration could be
      used to predict tumor development, progression, recurrence and therapeutic
      effects. The study was conducted on 80 epithelial ovarian carcinoma and 17
      control cases (normal ovarian and tubal tissues). TBX15 promoter methylation was
      first determined by pyrosequencing following bisulfite modification, then by
      cloning and sequencing, in order to obtain information about the epigenetic
      haplotype. Immunohistochemical analysis was performed to evaluate the correlation
      between the methylation and protein expression levels. Data revealed a
      statistically significant increase of the TBX15 promoter region methylation in
      82% of the tumor samples and in various histological subtypes.
      Immunohistochemistry showed an inverse correlation between methylation levels and
      the expression of the TBX15 protein. Furthermore, numerous tumor samples
      displayed varying degrees of intratumor heterogeneity. Thus, the present study
      determined that ovarian carcinoma typically expresses low levels of TBX15
      protein, predominantly due to an epigenetic mechanism. This may have a role in
      the pathogenesis of ovarian carcinoma independent of the histological subtype.

PMID- 27698864
TI  - Soluble purified recombinant C2ORF40 protein inhibits tumor cell growth in vivo
      by decreasing telomerase activity in esophageal squamous cell carcinoma.
AB  - The chromosome 2 open reading frame 40 (C2ORF40) gene is a candidate tumor
      suppressor gene for a variety of tumors. Previous results by the present authors
      revealed that the C2ORF40 protein is a secreted protein. However, the exact
      biological function of secreted C2ORF40 protein in carcinogenesis has not been
      thoroughly investigated. In the present study, the signal peptide sequence of the
      C2ORF40 cDNA was initially removed to produce secreted recombinant human C2ORF40
      protein (rhC2ORF40). Soluble rhC2ORF40 was successfully expressed and purified,
      which was evaluated for the first time, to the best of our knowledge, for tumor
      suppressing function in vivo in esophageal cancer. The present results revealed
      that soluble purified rhC2ORF40 was concentrated with a purity of >95%.
      Furthermore, rhC2ORF40 inhibited esophageal cancer cell growth in vivo in a dose
      dependent manner compared with a control group (P<0.05). In addition, the present
      study demonstrated for the first time that rhC2ORF40 decreased telomerase
      activity using telomeric repeat amplification protocol-enzyme-linked
      immunosorbent assay (P<0.05), without affecting the expression levels of
      telomerase-component RNA (P>0.05), as shown with polymerase chain reaction.
      Overall, the present results demonstrated that soluble rhC2ORF40 inhibited tumor
      cell growth in vivo by decreasing telomerase activity in esophageal squamous cell
      carcinoma. Therefore, soluble rhC2ORF40 with a high purity and biological
      activity may be a potential biological therapy drug for esophageal cancer.

PMID- 27698865
TI  - Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as
      neurocysticercosis: A case report.
AB  - Reports describing a rapid increase in the cystic volume of anaplastic
      astrocytoma (AA) in a short time frame are rare. The present study reports the
      case of a 68-year-old male who was admitted to the No. 9 People's Hospital,
      Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small
      cystic brain lesion and positive immunological testing for cysticercosis. Head
      magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the
      left frontal lobe. Neurocysticercosis was suspected and the patient was treated
      with a clinical trial of albendazole and steroids. A period of 25 days later, the
      patient's condition had deteriorated, and MRI revealed a cystic lesion in the
      left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of
      AA was established. The tumor was soft, ivory white and gelatinous due to myxoid
      degeneration. In this case, tumor-related angiogenesis and microvascular
      extravasation (blood-brain barrier disruption) may have been the main cause of
      the rapid increase in the cystic volume in such a short time frame. The
      similarity of the glioma and cysticercus antigens may have been the cause of the
      positive reactions in the cystic fluid. The present study reports the rare
      occurrence of a rapid increase of cystic volume and potential diagnostic
      difficulties.

PMID- 27698866
TI  - 4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl inhibits angiogenesis by
      suppressing VEGFR2 and Tie2 phosphorylation.
AB  - Reactive oxygen species (ROS) are involved in the signaling pathway and are
      triggered by angiogenic factors, including vascular endothelial growth factor and
      angiopoietins. 4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl (4-ISO
      Tempo) is one of the nitroxides that exhibits antioxidant activity. However, the
      anti-angiogenic effect of 4-ISO-Tempo remains unknown. The aim of this study was
      to investigate the effect of 4-ISO-Tempo on tumor proliferation and angiogenesis
      as well as its underlying mechanisms. Our results revealed that 4-ISO-Tempo
      significantly inhibited the viability of neoplastic and endothelial cells.
      Furthermore, the effective concentration of 4-ISO-Tempo on human microvascular
      endothelial cell 1 (HMEC-1) was lower than that on human lung adenocarcinoma A549
      and human colon cancer SW620 cells. This suggested that endothelial cells were
      more sensitive to 4-ISO-Tempo than tumor cells. Furthermore, we demonstrated that
      4-ISO-Tempo also suppressed secretion of matrix metalloproteinase (MMP)-2 and MMP
      9, and migration and tube formation of HMEC-1 cells. The mechanism is attributed
      to the decreasing ROS generation and further phosphorylation of vascular
      endothelial growth factor receptor 2 and Tie2. Our findings suggest that 4-ISO
      Tempo should be investigated for its usefulness in anti-angiogenesis therapies.

PMID- 27698867
TI  - Long non-coding RNA H19 promotes the proliferation of fibroblasts in keloid
      scarring.
AB  - The expression of the long non-coding RNA (lncRNA) H19 is associated with
      proliferation in tumors. In order to investigate whether H19 may additionally
      mediate the proliferation of fibroblasts in human keloid disease, the present
      study collected samples from 24 subjects, including 8 with keloids, 8 with normal
      scars and 8 normal skin controls. Reverse transcription-polymerase chain reaction
      revealed that H19 levels were markedly increased in human keloids compared with
      normal scars and normal skin controls (P=0.017). In order to identify a potential
      role for H19 in the proliferative activity of human keloid fibroblasts, small
      interfering (si)RNA-mediated silencing experiments were performed. H19 siRNA
      treatment markedly inhibited the proliferation of keloid fibroblasts, as assessed
      by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (P=0.008).
      In order to identify the signaling mediators that are regulated by H19 in keloid
      fibroblasts, the expression levels of mammalian target of rapamycin (mTOR) and
      vascular endothelial growth factor (VEGF) were examined using western blotting.
      The results confirmed that knockdown of H19 inhibited mTOR and VEGF expression.
      In summary, the results indicate that H19 may be associated with increased
      proliferative activity of keloid fibroblasts, which may be mediated by mTOR and
      VEGF.

PMID- 27698868
TI  - Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-kappaB.
AB  - In the present study, the effects and molecular mechanisms of thymoquinone (TQ)
      on colon cancer cells were investigated. Cell viability was determined using a
      Cell Counting Kit-8 assay, and the results revealed that treatment with TQ
      significantly decreased cell viability in COLO205 and HCT116 cells in a dose
      dependent manner. TQ treatment additionally sensitized COLO205 and HCT116 cells
      to cisplatin therapy in a concentration-dependent manner. To investigate the
      molecular mechanisms of TQ action, western blot analysis was used to determine
      the levels of phosphorylated p65 and nuclear factor-kappaB (NF-kappaB)-regulated
      gene products vascular endothelial growth factor (VEGF), c-Myc and B-cell
      lymphoma 2 (Bcl-2). The results indicated that TQ treatment significantly
      decreased the level of phosphorylated p65 in the nucleus, which indicated the
      inhibition of NF-kappaB activation by TQ treatment. Treatment with TQ also
      decreased the expression levels of VEGF, c-Myc and Bcl-2. In addition, the
      inhibition of NF-kappaB activation with a specific inhibitor, pyrrolidine
      dithiocarbamate, potentiated the induction of cell death and caused a
      chemosensitization effect of TQ in colon cancer cells. Overall, the results of
      the present study suggested that TQ induced cell death and chemosensitized colon
      cancer cells by inhibiting NF-kappaB signaling.

PMID- 27698869
TI  - RNA-seq analysis identifies key long non-coding RNAs connected to the
      pathogenesis of alcohol-associated head and neck squamous cell carcinoma.
AB  - Alcohol consumption has been implicated in the pathogenesis of head and neck
      squamous cell carcinoma (HNSCC), although its mechanism is poorly understood.
      Recent advances in the identification and understanding of long non-coding RNAs
      (lncRNAs) have indicated that these molecules have a profound effect on numerous
      biological processes, including tumorigenesis and oncogenesis. The present
      authors hypothesize that alcohol-mediated dysregulation of lncRNAs is a key event
      in HNSCC pathogenesis. An in silico differential expression analysis utilizing
      RNA sequencing (RNA-seq) data from 34 HNSCC patients, which included alcohol
      drinkers and non-alcohol drinkers, identified a panel of lncRNAs that were
      dysregulated due to alcohol consumption. Normal oral keratinocytes were then
      exposed to ethanol and acetaldehyde to validate the RNA-seq results. Two lncRNAs
      that were differentially expressed due to alcohol consumption were identified
      from RNA-seq analysis of the clinical data: lnc-PSD4-1 and lnc-NETO-1. Oral
      keratinocytes exposed to alcohol and acetaldehyde demonstrated dysregulation of
      these two lncRNAs, thus validating the results of RNA-seq analysis. In addition,
      low expression of the lnc-PSD4-1 isoform, lnc-PSD4-1:14, exhibited a strong
      correlation with high survival rates in a Cox proportional hazards regression
      model. Therefore, these lncRNAs may play a key role in the early pathogenesis of
      HNSCC, since they are dysregulated in both clinical data and in vitro experiments
      mimicking the effects of alcohol use.

PMID- 27698870
TI  - Association of FOXM1 expression with tumor histology and prognosis in Wilms
      tumor: Potential for a new prognostic marker.
AB  - Wilms tumor (WT) is the most common pediatric renal malignancy. A recent
      ontogenic model suggests that undifferentiated tumor state, and hence poor
      prognosis, in WT is determined by stabilization of beta-catenin in the nucleus.
      Forkhead box M1 (FOXM1) is a downstream component of the Wnt pathway and promotes
      nuclear localization of beta-catenin. As elevation of FOXM1 gene expression is
      prognostic in various types of malignancy, we hypothesized that high FOXM1
      expression in WT is associated with undifferentiated histology and thus poor
      prognosis. In the current study, the expression of FOXM1 mRNA was determined in
      46 WT specimens and 11 renal tissue controls from patients undergoing tumor
      nephrectomy, and these data were assessed with regard to clinicopathological
      parameters. The results demonstrated an upregulation of FOXM1 in WT by 10-fold
      compared to normal tissue. Expression differed significantly between controls and
      tumors of intermediate- and high-risk histopathology (P<0.001, Kruskal-Wallis),
      and distinguished normal tissue from tumors of good and adverse clinical outcome
      (P<0.001, Kruskal-Wallis). Notably, FOXM1 expression was significantly lower
      (P=0.009) in patients that received preoperative doxorubicin. These results
      suggest that FOXM1 may serve as a companion diagnostic factor for doxorubicin
      based therapies in WT.

PMID- 27698872
TI  - Radial forearm and forehead flap reconstruction following resection of a nasal
      arteriovenous malformation: A case report.
AB  - Arteriovenous malformation (AVM) is a structural vascular abnormality in which
      the arterial vasculature connects with the venous vasculature without capillary
      connections. AVM confined to the nasal cavity is considerably rare. Blurred
      vision can be one of the associated symptoms. A combined approach of complete
      surgical resection with prior superselective embolization is the treatment of
      choice. Following resection, the reconstruction of facial defects, particularly
      in the nasal area, is challenging. The present study reports the rare case of a
      patient with an AVM in the nasal cavity, in which embolization, resection and
      flap reconstruction were performed. Embolization and complete surgical resection
      were used to avoid recurrence. Subsequently, a combination of free radial forearm
      and forehead flaps was used for the reconstruction of the nasal defect, without
      prosthesis. To the best of our knowledge, this is the first report of AVM
      confined to the nasal cavity, managed by a combination of free radial forearm and
      forehead flap reconstruction following complete resection. The cosmetic results
      of the procedure were acceptable.

PMID- 27698871
TI  - Analysis of recurrence and survival rates in grade 3 endometrioid endometrial
      carcinoma.
AB  - The aim of the present study was to determine risk factors associated with
      recurrence and survival in patients with grade 3 endometrioid endometrial
      carcinoma (G3EEC). A retrospective analysis of 117 patients with G3EEC, who were
      admitted to the Obstetrics and Gynecology Hospital of Fudan University between
      January 2000 and December 2011, was performed. The chi2 test or Fisher's exact
      test were used for the comparison of categorical variables. Kaplan-Meier method
      was used for estimating recurrence-free survival (RFS), disease-specific survival
      (DSS) and overall survival (OS) rates. Univariate and multivariate Cox
      proportional hazards model were used to assess the prognostic significance of
      various patient characteristics. In 117 patients, 16 patients (13.7%) had tumor
      recurrence, of which 6 (37.5%) developed local-regional recurrence and 10 (62.5%)
      developed distant recurrence. Out of the 16 patients with tumor recurrence, 14
      (87.5%) had a recurrence within 3 years of surgery. Statistically significant
      characteristics affecting RFS, DSS and OS rates were outer half myometrial
      invasion (MI >=50%), advanced International Federation of Gynecology and
      Obstetrics stage, positive lymph node metastasis (PLNM), lymph vascular space
      invasion, adnexal involvement and characterization as a high-risk group,
      according to the Gynecologic Oncology Group 99 stratification algorithm. RFS was
      associated with the depth of cervical mucosa (stromal) involvement. Furthermore,
      in the multivariate Cox proportional hazards model, significant independent
      adverse factors for RFS and DSS included MI >=50% and adnexal involvement. For
      OS, there were no statistically significant prognostic factors. In conclusion, MI
      >=50% and adnexal involvement are independent prognostic factors for RFS and DSS
      in G3EEC patients.

PMID- 27698873
TI  - Investigation of the association between mitochondrial DNA and p53 gene mutations
      in transitional cell carcinoma of the bladder.
AB  - Bladder carcinoma is the most common malignancy of the urinary tract. The major
      aim of the present study is to investigate the association between mitochondrial
      DNA (mtDNA) and p53 gene mutations in bladder carcinoma. A total of 30 patients
      with transitional cell carcinoma and 27 controls were recruited for the study.
      Bladder cancer tissues were obtained by radical cystectomy or transurethral
      resection. Genomic DNA was extracted from peripheral blood. mtDNA and p53 genes
      were amplified by polymerase chain reaction and sequenced directly. A total of 37
      polymorphisms were identified, among which, 2 mutations were significant in the
      patient group, and 1 mutation was significant in the control group. Additionally,
      5 different moderate positive correlations between mtDNA mutations and 3
      different positive correlations between p53 gene and mtDNA mutations were
      detected. The high incidence of mtDNA and p53 gene mutations in bladder cancer
      suggests that these genes could be important in carcinogenesis.

PMID- 27698874
TI  - Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated
      mitochondrial translocation of cofilin-1 in prostate cancer.
AB  - Ursolic acid is a type of pentacyclic triterpene compound with multiple
      pharmacological activities including cancer resistance, protection from liver
      injury, antisepsis, anti-inflammation and antiviral activity. The present study
      aimed to investigate the anticancer effect of ursolic acid. Ursolic acid
      activates cell apoptosis and its pro-apoptotic mechanism remains to be fully
      elucidated. Cell Counting kit-8 assays, flow cytometric analysis and analysis of
      caspase-3 and caspase-9 activity were used to estimate the anticancer effect of
      ursolic acid on DU145 prostate cancer cells. The protein expression of cytochrome
      c, rho-associated protein kinase (ROCK), phosphatase and tensin homolog (PTEN)
      and cofilin-1 were examined using western blot analysis. In the present study,
      ursolic acid significantly suppressed cell growth and induced apoptosis, as well
      as increasing caspase-3 and caspase-9 activities of DU145 cells. Furthermore,
      cytoplasmic and mitochondrial cytochrome c protein expression was significantly
      activated and suppressed, respectively, by ursolic acid. Ursolic acid
      significantly suppressed the ROCK/PTEN signaling pathway and inhibited cofilin-1
      protein expression in DU145 cells. The results of the present study indicate that
      the anticancer effect of ursolic acid activates cell apoptosis through ROCK/PTEN
      mediated mitochondrial translocation of cofilin-1 in prostate cancer.

PMID- 27698875
TI  - Side population cells from long-term passage non-small cell lung cancer cells
      display loss of cancer stem cell-like properties and chemoradioresistance.
AB  - The side population (SP) assay is a widely used method for isolating stem cell
      like cells from cancer cell lines and primary cells. The cancer cells used in
      different laboratories have been passaged for different generations. Emerging
      evidence revealed that repeated passaging of cell lines for multiple generations
      frequently leads to change of characteristics. Thus, it is worth investigating
      the effects of repeated passaging on the biological and functional properties of
      the enriched SP fraction from early- and late-passage cells. The present study
      reports that the cancer stem cell (CSC) characteristics, including increased
      frequency of tumor-initiating and self-renewal capacity, and resistance to the
      chemotherapy agent doxorubicin and ionizing radiation, was diminished in SP cells
      from late-passage non-small cell lung cancer (NSCLC) cells. This finding revealed
      that the SP from long-term passage NSCLC cells was not consistently enriched for
      stem cell-like cancer cells, and low-passage cell lines and primary cancer cells
      are therefore recommended in the CSCs field.

PMID- 27698876
TI  - Eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and
      PI3K/AKT signaling pathways.
AB  - Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase
      (MAPK) signaling cascades have significant roles in cell proliferation, survival,
      angiogenesis and metastasis of tumor cells. Eupatilin, one of the major compounds
      present in Artemisia species, has been demonstrated to have antitumor properties.
      However, the effect of eupatilin in renal cell carcinoma (RCC) remains to be
      elucidated. Therefore, the present study investigated the biological effects and
      mechanisms of eupatilin in RCC cell apoptosis. The results of the present study
      demonstrated that eupatilin significantly induced cell apoptosis and enhanced the
      production of reactive oxygen species (ROS) in 786-O cells. In addition,
      eupatilin induced phosphorylation of p38alpha (Thr180/Tyr182), extracellular
      signal-regulated kinase 1/2 and c-Jun N-terminal kinase 1/2 (Thr183/Tyr185), and
      decreased the phosphorylation of PI3K and AKT in 786-O cells in a concentration
      dependent manner. Furthermore, the ROS inhibitor N-acetyl-L-cysteine was able to
      rescue the MAPK activation and PI3K/AKT inhibition induced by eupatilin. Taken
      together, the results of the present study provide evidence that inhibition of
      eupatilin induces apoptosis in human RCC via ROS-mediated activation of the MAPK
      signaling pathway and inhibition of the PI3K/AKT signaling pathway. Thus,
      eupatilin may serve as a potential therapeutic agent for the treatment of human
      RCC.

PMID- 27698877
TI  - Inhibition of gamma-secretase activity synergistically enhances tumour necrosis
      factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute
      lymphoblastic leukemia cells via upregulation of death receptor 5.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive
      hematopoietic malignancy prone to relapse and drug resistance. Half of all T-ALL
      patients exhibit mutations in Notch1, which leads to aberrant Notch1 associated
      signaling cascades. Notch1 activation is mediated by the gamma-secretase cleavage
      of the Notch1 receptor into the active intracellular domain of Notch1 (NCID).
      Clinical trials of gamma-secretase small molecule inhibitors (GSIs) as single
      agents for the treatment of T-ALL have been unsuccessful. The present study
      demonstrated, using immunofluorescence and western blotting, that blocking gamma
      secretase activity in T-ALL cells with N-[(3,5-difluorophenyl) acetyl]-L-alanyl-2
      phenyl] glycine-1,1-dimethylethyl ester (DAPT) downregulated NCID and upregulated
      the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death
      receptor 5 (DR5). Upregulation of DR5 restored the sensitivity of T-ALL cells to
      TRAIL. Combination index revealed that the combined treatment of DAPT and TRAIL
      synergistically enhanced apoptosis compared with treatment with either drug
      alone. TRAIL combined with the clinically evaluated gamma-secretase inhibitor 3
      [(1r, 4s)-4-(4-chlorophenylsulfonyl)-4-(2, 5-difluorophenyl) cyclohexyl]
      propanoic acid (MK-0752) also significantly enhanced TRAIL-induced cell death
      compared with either drug alone. DAPT/TRAIL apoptotic synergy was dependent on
      the extrinsic apoptotic pathway and was associated with a decrease in BH3
      interacting-domain death agonist and x-linked inhibitor of apoptosis. In
      conclusion, gamma-secretase inhibition represents a potential therapeutic
      strategy to overcome TRAIL resistance for the treatment of T-ALL.

PMID- 27698879
TI  - A sesquiterpene lactone from Siegesbeckia glabrescens suppresses Hedgehog/Gli
      mediated transcription in pancreatic cancer cells.
AB  - Pancreatic cancer is aggressive and therefore difficult to treat; however,
      continued efforts have been made with the aim of developing an effective therapy
      against the disease. The Hedgehog (Hh) signaling pathway is reportedly involved
      in the proliferation and survival of pancreatic cancer cells. The transcription
      factor glioma-associated oncogene (Gli) is a key component of the Hh signaling
      pathway and the primary effector of pancreatic cancer development. Inhibiting Gli
      is a proven therapeutic strategy for this disease. The present study examined the
      regulation of Gli and the expression of its target genes to identify an inhibitor
      of the Sonic Hh (Shh) pathway. A germacranolide sesquiterpene lactone (GSL) was
      isolated from Siegesbeckia glabrescens as an inhibitor of Gli-mediated
      transcription. The results demonstrated that GSL inhibited Shh-induced osteoblast
      differentiation and Gli homolog 1 (Gli1)-mediated transcriptional activity in
      mesenchymal C3H10T1/2 stem cells. Furthermore, GSL suppressed Gli-mediated
      transcriptional activity in human pancreatic cancer PANC-1 and AsPC-1 cells,
      which resulted in reduced cancer cell proliferation and downregulated expression
      of the Gli-target genes, Gli1 and cyclin D1. A sesquiterpene lactone from S.
      glabrescens may therefore serve as a candidate for the treatment of Hh/Gli
      dependent pancreatic cancer.

PMID- 27698878
TI  - Tumor-suppressing effects of microRNA-429 in human renal cell carcinoma via the
      downregulation of Sp1.
AB  - MicroRNA (miR)-429 has been frequently reported to be downregulated in various
      tumors, including renal cell carcinoma (RCC), nasopharyngeal carcinoma, Ehrlich
      ascites tumor cells, gastric cancer, non-small cell lung cancer and endometrial
      endometrioid carcinoma. The present study investigated the effects of miR-429 on
      human RCC A498 and 786-O cells. Following transfection of cells with miR-429
      mimics and scrambled control, MTT, cell migration, cell invasion and luciferase
      assays were performed. In addition, western blotting was performed in order to
      assess the expression of specificity protein 1 (Sp1), which was predicted to be a
      target of miR-429 by TargetScan. The present results revealed that miR-429
      inhibited cell proliferation, migration and invasion of 786-O and A498 cells. In
      addition, the present results demonstrated that miR-429 overexpression
      downregulated Sp1 protein expression, which provides evidence that miR-429 may
      directly target Sp1 in RCC. These results suggest that miR-429 may be
      investigated for use as a predictive marker for early detection of tumor
      metastasis and blocking RCC cells from becoming invasive.

PMID- 27698880
TI  - Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate
      cancer cells.
AB  - Deoxypodophyllotoxin (DPPT) is extracted and separated from citrus-related
      plants, including Podophyllum (P.) peltatum, P. pleianthum, P. emodi (also called
      P. hexandrum) and Diphylleia grayi. DPPT has significant antitumor and antiviral
      activity. However, due to its strong toxicity and side effects, its use is
      limited in practical applications. The in vitro antitumor efficacy of DPPT on
      human prostate cancer (PCa) cells remains to be determined. The present study
      investigated the anticancer effect of DPPT on human PCa cells and its potential
      mechanism. The data revealed that DPPT markedly reduced cell proliferation and
      activated the caspase-3 expression level by an increase in apoptotic cell death
      in DU-145 cells. In addition, treatment with DPPT markedly downregulated the
      levels of phosphorylated Akt and activated the p53/B-cell lymphoma 2 associated X
      protein (Bax)/phosphatase and tensin homolog (PTEN) signaling pathway in DU-145
      cells, suggesting that caspase-mediated pathways were involved in DPPT-induced
      apoptosis. The present study suggested the role of DPPT as a novel
      chemotherapeutic drug for human PCa, which may function through the
      Akt/p53/Bax/PTEN signaling pathway.

PMID- 27698882
TI  - Metastatic extraskeletal Ewing's sarcoma treated with trabectedin: A case report.
AB  - The Ewing's sarcoma family of tumors (ESFT) comprises a number of rare malignant
      tumors. Standard first-line treatment for patients with these tumors includes
      chemotherapy with a five-drug regimen of vincristine, doxorubicin (Adriamycin(r))
      and cyclophosphamide, alternating with ifosfamide and etoposide (VAC/IE). In
      cases of inadequate response, there are a number of second-line regimens
      available. However, further treatment options are required for those patients
      with disease unresponsive to standard treatment. Trabectedin is a novel treatment
      option for patients with ESFT. The present study reports the case of a Caucasian
      69-year-old female patient who presented with a soft tissue mass on the chest
      wall that had developed 7 months earlier. A computed tomography scan revealed a
      9*8*7-cm mass on the anterior chest wall above the pectoral muscle.
      Histopathological evaluations and molecular analysis indicated that it was
      consistent with a metastatic extraskeletal Ewing's sarcoma. The patient was
      treated with an alternating VAC/IE regimen; however, an inadequate response was
      observed. The patient received second-line treatment with a gemcitabine and
      dacarbazine combination regimen, but the disease progressed. Subsequently,
      treatment with trabectedin (1.5 mg/m2 as a 24-h continuous infusion every 3
      weeks) was initiated. Trabectedin treatment resulted in long-lasting (18 months)
      progression-free survival. It is vital that novel drugs continue to being
      developed for patients with ESFT following progression subsequent to standard
      chemotherapy. The current report presents a case of a patient with metastatic,
      pre-treated Ewing's sarcoma achieving disease stabilization with trabectedin.
      Based on these results and the observed tolerability profile, trabectedin
      represents an alternative treatment for patients with ESFT. Further studies are
      required in order to determine the efficacy of trabectedin as monotherapy or in
      combination with other drugs. It is also important to identify which tumor
      subtypes, specific translocations and patient profiles will benefit the most from
      treatment with trabectedin.

PMID- 27698881
TI  - Impact of intense systemic therapy and improved survival on the use of palliative
      radiotherapy in patients with bone metastases from prostate cancer.
AB  - More effective drugs may reduce the requirement for palliative external beam
      radiotherapy for bony target volumes; however, living with metastases for
      prolonged periods of time may result in more frequent episodes of bone pain or
      serious skeletal-related events. The purpose of the present study was to evaluate
      how recent advances in systemic therapy impact radiotherapy utilization. A
      retrospective analysis of a comprehensive regional database was performed. All
      oncology care in this region was provided by only one center, assuring complete
      data. Patients that had succumbed between June 1, 2004 and June 1, 2015 were
      included. For all 236 patients, the median age at diagnosis of bone metastases
      was 75 years and median overall survival was 20 months. More intense systemic
      therapy was associated with a significantly longer survival time. Only 69
      patients (29%) did not receive palliative radiotherapy for bony target volumes,
      whilst 1 course was given to 101 patients (43%), 2 courses to 34 patients (14%)
      and >2 courses to 32 patients (14%). Radiotherapy was used more frequently in
      younger patients, those with spinal cord compressions or pathological fractures,
      and those treated with intense and long-standing systemic therapy. Radiotherapy
      utilization increased with survival time. For 100 poor-prognosis patients that
      succumbed within 12 months, 57 courses of palliative radiotherapy were
      administered, whilst 100 patients that survived for 12-24 months were
      administered 114 courses (24-36 months, 148 courses). In conclusion, the use of
      palliative radiotherapy did not decrease when more effective systemic therapy was
      administered. However, provided that only 5% of patients received radionuclide
      treatment, additional studies in other populations are required.

PMID- 27698883
TI  - Identification of candidate target genes of genomic aberrations in esophageal
      squamous cell carcinoma.
AB  - The aim of the present study was to identify the candidate target genes of
      genomic aberrations in esophageal squamous cell carcinoma (ESCC). Array
      comparative genomic hybridization (CGH) and quantitative polymerase chain
      reaction were applied to analyze the copy number changes and expression level of
      candidate genes, respectively. Integrative analysis revealed that homozygous
      deletions of cyclin-dependent kinase inhibitor (CDKN) 2A and CDKN2B and gains of
      fascin actin-bundling protein 1 (FSCN1) and homer scaffolding protein 3 (HOMER3)
      occurred frequently in ESCC. The results demonstrated that the homozygous
      deletion of CDKN2A or CDKN2B was significantly associated with lymph node
      metastasis. Notably, the expression of CDKN2A and CDKN2B was lower in dysplasia
      than in normal esophageal epithelium. We also observed that the copy number
      increase of FSCN1 was significantly associated with pT, pN and pStage, and that
      the gain of HOMER3 was significantly linked with pN and pStage. We further
      revealed that FSCN1 and HOMER3 were overexpressed in ESCC, and that their
      overexpression was correlated with copy number increase. In conclusion, CDKN2A,
      CDKN2B, FSCN1 and HOMER3 are candidate cancer-associated genes and may play a
      tumorigenic role in ESCC.

PMID- 27698884
TI  - Comparable roles of CD44v8-10 and CD44s in the development of bone metastases in
      a mouse model.
AB  - Cluster of differentiation (CD)44 has been implicated in cancer metastasis to
      bone. Clinical and experimental studies have suggested that the standard isoform
      of CD44 (CD44s) and the variant isoform of CD44 (CD44v) enhance metastasis. The
      present study examined the differential roles of CD44s and CD44v, particularly
      CD44v8-10, in the development of bone metastases. For this purpose, MDA-MB-231
      human breast cancer cells and A549 human lung cancer cells were stably transduced
      with epithelial splicing regulatory protein 1 (ESRP1), which regulates the
      alternative splicing of several genes, including CD44. The introduction of ESRP1
      induced a splicing switch from CD44s to CD44v, particularly to CD44v8-10, while
      the total amount of CD44 was rarely affected. However, ESRP1 did not
      significantly affect cell proliferation, migration, invasion or tumor sphere
      formation in vitro. Furthermore, ESRP1 did not cause significant differences in
      the development of bone metastases in a mouse model. As an alternative approach,
      cancer cells transduced with the CD44v8-10 gene were also established. The
      overexpression of CD44v8-10 in MCF-7 human breast cancer cells, which rarely
      express any isoform of CD44, promoted cell migration and sphere formation,
      whereas the overexpression of CD44v8-10 in MDA-MB-231 cells, which endogenously
      express high levels of CD44s, did not exert these effects. The results of the
      present study collectively suggest that the ability of CD44v8-10 to promote tumor
      aggressiveness and bone metastases is similar to that of CD44s. CD44v8-10 and
      CD44s may represent potential therapeutic targets for the treatment of bone
      metastases.

PMID- 27698885
TI  - RANKL: A promising circulating marker for bone metastasis response.
AB  - Bone metastases are a frequent event in patients with solid tumors. Although
      great advances have been made in the treatment of these patients, the
      identification of novel, accurate indicators of bone response would greatly
      facilitate the clinical management of the disease. The receptor activator of
      nuclear factor-kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling
      pathway is significantly involved in bone metastasis formation. The main aim of
      the present study was to evaluate the role of circulating RANK, RANKL and OPG
      levels in predicting bone response. Marker accuracy was also compared with that
      of the conventional tumor marker N-terminal telopeptide of type I collagen (NTX).
      A prospective study was performed on 49 patients with bone metastases from
      breast, lung and prostate cancer, who were undergoing treatment with zoledronic
      acid. Patients were monitored for 1 year with blood tests, clinical evaluation
      and instrumental exams according to the response evaluation criteria of the
      University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the
      Positron Emission Tomography Response Criteria in Solid Tumors. Circulating
      RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription
      quantitative polymerase chain reaction and immune enzymatic assay, respectively.
      The baseline RANKL levels differed significantly between responders and non
      responders, whereas no differences in NTX levels were observed between the two
      groups. Receiver operating characteristic curve evaluation for all markers
      revealed that RANKL was the most accurate marker, with an area under the curve of
      0.74 (95% confidence interval, 0.54-0.93). In addition, RANKL, which is the
      target of the novel monoclonal antibody denosumab, was the most accurate
      predictor of bone response in the present series of patients with bone
      metastases. Thus, the use of RANKL as a marker could potentially improve clinical
      practice, as current bone response evaluation is still somewhat problematic.

PMID- 27698886
TI  - Programmed cell death 4 and BCR-ABL fusion gene expression are negatively
      correlated in chronic myeloid leukemia.
AB  - Programmed cell death 4 (PDCD4) is a tumor suppressor that inhibits
      carcinogenesis, tumor progression and invasion by preventing gene transcription
      and translation. Downregulation of PDCD4 expression has been identified in
      multiple types of human cancer, however, to date, the function of PDCD4 in
      leukemia has not been investigated. In the present study, PDCD4 mRNA and protein
      expression was investigated in 50 patients exhibiting various phases of chronic
      myeloid leukemia (CML) and 20 healthy individuals by reverse transcription
      quantitative polymerase chain reaction and western blot analysis. PDCD4
      expression and cell proliferation was also investigated following treatment with
      the tyrosine kinase inhibitor, imatinib, in K562 cells. The results demonstrated
      that PDCD4 mRNA and protein expression was decreased in all CML samples when
      compared with healthy controls, who expressed high levels of PDCD4 mRNA and
      protein. No significant differences in PDCD4 expression were identified between
      chronic phase, accelerated phase and blast phase CML patients. In addition, PDCD4
      expression was negatively correlated with BCR-ABL gene expression (r=-0.6716;
      P<0.001). Furthermore, K562 cells treated with imatinib exhibited significantly
      enhanced PDCD4 expression. These results indicate that downregulation of PDCD4
      expression may exhibit a critical function in the progression and malignant
      proliferation of human CML.

PMID- 27698887
TI  - Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and
      motility.
AB  - Hedera helix L., a member of Araliaceae family, has antiproliferative, cytotoxic,
      antimicrobial, antifungal, antiprotozoal and anti-inflammatory effects, and is
      used in cosmetics. The aim of the present study was to investigate the effect of
      treatment with extracts of leaves and unripened fruits of H. helix on rat
      prostate cancer cell lines with markedly different metastatic potentials: Mat
      LyLu cells (strongly metastatic) and AT-2 cells (weakly metastatic). The effects
      of the extracts on cell kinetics and migration were determined. Tetrodotoxin was
      used to block the voltage-gated sodium channels (VGSCs) associated specifically
      with Mat-LyLu cells. Cell proliferation was detected spectrophotometrically using
      the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The
      mitotic index was determined using the Feulgen staining method. Lateral motility
      was quantified by wound-healing assays. The results of the present study
      demonstrated that cell kinetics (proliferation and mitotic activity) and motility
      were inhibited by ethanolic leaf extract of H. helix. The ethanolic extract of H.
      helix fruit suppressed Mat-LyLu cell migration, with no effect on proliferation.
      The opposite effects were observed in AT-2 cells; migration was not affected but
      proliferation was inhibited. In conclusion, the ethanolic fruit extract of H.
      helix may inhibit the cell migration of Mat-LyLu cells by blocking VGSCs.
      However, the effect of ethanolic leaf extract of H. helix treatment on the
      lateral motility of the cancer cells is unclear.

PMID- 27698888
TI  - miRNA regulation of Sirtuin-1 expression in human astrocytoma.
AB  - Sirtuins are a family of 7 histone deacetylases largely involved in the
      regulation of cell proliferation, survival and death. The role of sirtuins in
      tumorigenesis and cancer progression has been previously studied in certain
      cancer types. Few studies have investigated sirtuin expression in gliomas, with
      controversial results. The aim of the present study was to investigate the
      expression of sirtuin-1 (Sirt-1) in diffuse astrocytoma [low grade astrocytoma
      (LGA)], anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) and in
      primary glioma cell lines: PLGAC (primary LGA cells); PAAC (primary AA cells);
      and PGBMC (primary GBM cells). Tumor samples were obtained from patients who
      underwent craniotomy for microsurgical tumor resection at the Neurosurgery Unit
      of the University of Messina between 2011 and 2014. Sirt-1 expression was
      qualitatively analyzed in 30 human glial tumor samples and 5 non-neoplastic brain
      tissue (NBT) specimens using immunohistochemistry and western blotting
      techniques. Sirt-1 expression was quantitatively analyzed by reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, Sirt
      1 expression in primary cell lines was investigated by immunoblotting and RT
      qPCR. Sirt-1 expression was downregulated in gliomas compared to NBTs. Sirt-1
      levels also varied among different tumor grades, with more evident downregulation
      in high-grade (P<0.001) than low-grade tumors (P<0.01). These data were confirmed
      in cell lines, with the exception of upregulation of protein level in the highest
      malignancy grade cell lines. The present results suggest a role for miRNA-34a,
      miRNA-132 and miRNA-217 in the epigenetic control of Sirt-1 during gliomagenesis
      and progression, and demonstrate the different implications of Sirt-1 in human
      tissues and cell lines. Furthermore, the present results reveal that Sirt-1 may
      be an intrinsic regulator of tumor progression and the regulation of Sirt-1
      involves complex molecular pathways. However, the biological functions of Sirt-1
      in gliomagenesis require additional investigation.

PMID- 27698889
TI  - TGFB2 and BCL2L11 methylation in male laryngeal cancer patients.
AB  - DNA methylation is a major regulatory mechanism of gene expression. The aim of
      the present study was to test the association of transforming growth factor beta2
      (TGFB2) and B cell lymphoma 2-like 11 (BCL2L11) gene methylation with the risk of
      laryngeal squamous cell carcinoma (LSCC). Using bisulfite pyrosequencing
      technology, DNA methylation levels of TGFB2 promoter and BCL2L11 gene-body CpG
      cytosines were measured in 90 LSCC tissues and 90 adjacent normal tissues.
      Analysis of variance and paired sample t-test were used to determine the
      association of gene methylation and the risk of LSCC. Our results revealed that
      there were no differences in TGFB2 and BCL2L11 methylation levels between the
      LSCC tissues and the paired normal tissues (P>0.05). Further breakdown analyses
      demonstrated that the association results of the two gene methylation levels and
      LSCC remained unchanged with the age, smoking history, histological
      differentiation or clinical stage of the LSCC patients (all adjusted P>0.05). In
      conclusion, there is no association of TGFB2 promoter and BCL2L11 gene-body
      methylation with the risk of LSCC in males.

PMID- 27698890
TI  - Quantitative detection of TUSC3 promoter methylation -a potential biomarker for
      prognosis in lung cancer.
AB  - Aberrant promoter methylation of tumor relevant genes frequently occurs in early
      steps of carcinogenesis and during tumor progression. Epigenetic alterations
      could be used as potential biomarkers for early detection and for prediction of
      prognosis and therapy response in lung cancer. The present study quantitatively
      analyzed the methylation status of known and potential gatekeeper and tumor
      suppressor genes [O-6-methylguanine-DNA methyltransferase (MGMT), Ras association
      domain family member 1A (RASSF1A), Ras protein activator like 1 (RASAL1),
      programmed cell death 4 (PDCD4), metastasis suppressor 1 (MTSS1) and tumor
      suppressor candidate 3 (TUSC3)] in 42 lung cancers and in corresponding non
      malignant bronchus and lung tissue using bisulfite-conversion independent
      methylation-quantification of endonuclease-resistant DNA (MethyQESD). Methylation
      status was associated with clinical and pathological parameters. No methylation
      was found in the promoter regions of PDCD4 and MTSS1 of either compartment. MGMT,
      RASSF1A and RASAL1 showed sporadic (up to 26.2%) promoter methylation. The
      promoter of TUSC3, however, was frequently methylated in the tumor (59.5%),
      benign bronchus (67.9%) and alveolar lung (31.0%) tissues from each tumor
      patient. The methylation status of TUSC3 was significantly associated with
      smaller tumor size (P=0.008) and a longer overall survival (P=0.013). Pooled
      blood DNA of healthy individuals did not show any methylation of either gene.
      Therefore, methylation of TUSC3 shows prognostic and pathobiological relevance in
      lung cancer. Furthermore, quantitative detection of TUSC3 promoter methylation
      appears to be a promising tool for early detection and prediction of prognosis in
      lung cancer. However, additional studies are required to confirm this finding.

PMID- 27698891
TI  - MMP-14 and TGFbeta-1 methylation in pituitary adenomas.
AB  - Pituitary adenoma (PA) is one of the most common abnormalities in the sellar
      region. Despite the fact that PA is a benign monoclonal neoplasm, it can cause
      serious complications, including ophthalmological, neurological and
      endocrinological abnormalities. Currently, the causes that increase the
      progression of tumors are unknown. Epigenetic silencing of the matrix
      metalloproteinase-14 (MMP-14) and transforming growth factor beta-1 (TGFbeta-1)
      genes may be associated with the development of PA, since these genes are
      important in the processes of tumor metastasis and angiogenesis. The purpose of
      the present study was to determine if the methylation status of the MMP-14 and
      TGFbeta-1 promoters is associated with PA development. In the present study, 120
      tissue samples of PA were used. The methylation status of the MMP-14 and TGFbeta
      1 promoters was investigated by methylation specific-polymerase chain reaction.
      Statistical analysis was conducted to investigate the associations between the
      methylation status, age and gender of PA patients, PA tumoral activity,
      recurrence and invasiveness. The MMP-14 gene was methylated in 30.00% (17/56
      functioning and 19/64 non-functioning) of patients with PA, while the TGFbeta-1
      gene was methylated in 13.33% (9/56 functioning and 7/64 non-functioning) of
      patients with PA. It was also observed that promoter methylation of MMP-14
      correlated with the male gender (58.8 vs. 35.7%, P=0.022), while unmethylated
      (non-silenced) MMP-14 correlated with the female gender (64.3 vs. 41.7%,
      P=0.027). Associations between the promoter methylation status of the MMP-14 and
      TGFbeta-1 genes and PA functioning or recurrence were not identified. The present
      study reveals that silencing of the MMP-14 gene correlates with patients' gender.
      However, MMP-14 and TGFbeta-1 promoter methylation cannot be considered as a
      prognostic marker in PAs.

PMID- 27698892
TI  - Atypical presentation of a gastric stromal tumor masquerading as a giant
      intraabdominal cyst: A case report.
AB  - Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms that arise in
      the gastrointestinal tract, accounting for ~1% of gastric malignancies. The
      present study reports the case of a GIST of the stomach in a 75-year-old man who
      presented with abdominal distension and anorexia for 1 month. Gastroscopy was
      unremarkable. Ultrasound and computed tomography (CT) scans showed a giant
      intraabdominal cystic lesion of unknown origin. The lesion was initially believed
      to be a duplication cyst, a pancreatic pseudocyst or a liver cyst in the pre
      operative diagnosis. Exploratory laparotomy revealed a cystic lesion of the
      lesser sac originating from the lesser curvature of the stomach. A distal
      gastrectomy with en bloc resection of the lesion was performed. The
      intraoperative frozen section showed a spindle-cell GIST and microscopically
      negative margins. The patient was treated with imatinib for 1 year. The latest CT
      scan at 14 months post-surgery did not show any recurrence. Although GISTs
      presenting as predominantly cystic lesions are very rare, they should be
      considered in the differential diagnosis of cystic lesions of the upper abdomen.

PMID- 27698893
TI  - miR-143 is associated with proliferation and apoptosis involving ERK5 in HeLa
      cells.
AB  - Inappropriate expression of microRNA (miR) is strongly associated with
      carcinogenesis. miR-143 was reported to be one of the most prominent miRs
      implicated in the genesis and progression of human cancer. However, its
      correlation with cell proliferation and apoptosis in cervical cancer remains to
      be fully elucidated. In the present study, it was demonstrated that miR-143 is
      able to suppress the proliferation of cervical cancer HeLa cells and induce cell
      apoptosis in a time- and dose-dependent manner. The present study also
      investigated the potential targets of miR-143, extracellular-signal-regulated
      kinase 5 (ERK5) and its downstream substrate oncoprotein c-Fos, both of which are
      involved in cell proliferation and apoptosis. Upon increasing the miR-143 level,
      the ERK5 and c-Fos protein expression was significantly decreased without the
      effect of ERK5 transcription. Therefore, miR-143 is able to suppress cell
      proliferation and induce apoptosis in HeLa cells, potentially through negative
      regulation of ERK5 at its post-transcriptional stage.

PMID- 27698894
TI  - AKT-STAT3 Pathway as a Downstream Target of EGFR Signaling to Regulate PD-L1
      Expression on NSCLC cells.
AB  - While cancer development and progression can be controlled by cytotoxic T cells,
      it is also known that tumor-specific CD8+T cells become functionally impaired by
      acquiring a group of inhibitory receptors known as immune checkpoints. Amongst
      those, programmed death-1 (PD-1) is one of the most recognized negative
      regulators of T cell function. In non-small lung cancers (NSCLCs), the aberrant
      activation of epidermal growth factor receptor (EGFR) is known to induce PD-L1
      expression and further the treatment with gefitinib, a tyrosine kinase inhibitor
      (TKI) for EGFR, decrease the expression of PD-L1 on NSCLC. Given the acquired
      resistance to gefitinib treatment frequently observed by developing secondary
      site mutations limiting its efficacy, it is important to understand the
      downstream mechanism of activated-EGFR signaling for regulating PD-L1 in NSCLC.
      In this study, we demonstrated that AKT-STAT3 pathway could be a potential target
      for regulating the surface expression of PD-L1 on NSCLCs with aberrant EGFR
      activity and, further, the inhibition of AKT or STAT3 activity could down
      regulate the expression of PD-L1 even in gefitinib-resistant NSCLCs. These
      results highlight an importance of AKT-STAT3 pathway as a promising target for
      potentiating anti-tumor immune responses by regulating PD-L1 expression on cancer
      cells with aberrant EGFR activity.

PMID- 27698895
TI  - African American Race is an Independent Risk Factor in Survival from Initially
      Diagnosed Localized Breast Cancer.
AB  - BACKGROUND: African American race negatively impacts survival from localized
      breast cancer but co-variable factors confound the impact. METHODS: Data sets
      were analyzed from the Surveillance, Epidemiology and End Results (SEER)
      directories from 1973 to 2011 consisting of patients with designated diagnosis of
      breast adenocarcinoma, race as White or Caucasian, Black or African American,
      Asian, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander,
      age, stage I, II or III, grade 1, 2 or 3, estrogen receptor or progesterone
      receptor positive or negative, marital status as single, married, separated,
      divorced or widowed and laterality as right or left. The Cox Proportional Hazards
      Regression model was used to determine hazard ratios for survival. Chi square
      test was applied to determine the interdependence of variables found significant
      in the multivariable Cox Proportional Hazards Regression analysis. Cells with
      stratified data of patients with identical characteristics except African
      American or Caucasian race were compared. RESULTS: Age, stage, grade, ER and PR
      status and marital status significantly co-varied with race and with each other.
      Stratifications by single co-variables demonstrated worse hazard ratios for
      survival for African Americans. Stratification by three and four co-variables
      demonstrated worse hazard ratios for survival for African Americans in most
      subgroupings with sufficient numbers of values. Differences in some subgroupings
      containing poor prognostic co-variables did not reach significance, suggesting
      that race effects may be partly overcome by additional poor prognostic
      indicators. CONCLUSIONS: African American race is a poor prognostic indicator for
      survival from breast cancer independent of 6 associated co-variables with
      prognostic significance.

PMID- 27698896
TI  - Current Status and Perspective of Immunotherapy in Gastrointestinal Cancers.
AB  - Cancer immunotherapy is at dawn of the Renaissance after the Medieval Dark Ages.
      Recent advances of understanding tumor immunology and molecular drug development
      are leading us to the epoch of cancer immunotherapy. Some types of immunotherapy
      have shown to provide survival benefit for patients with solid tumors such as
      malignant melanoma, renal cell carcinoma, or non-small cell lung cancer. Several
      studies have suggested that immune checkpoint inhibition might be effective in
      some patients with gastrointestinal cancers. However, the era of cancer
      immunotherapy in gastrointestinal cancers is still in an inchoate stage. Here we
      briefly review the current status and perspective of immunotherapeutic approaches
      in patients with gastrointestinal cancers.

PMID- 27698897
TI  - Differential Roles of Carboxylated and Uncarboxylated Osteocalcin in Prostate
      Cancer Growth.
AB  - Serum levels of osteocalcin (OC), a bone matrix non-collagenous protein secreted
      by osteoblasts, are correlated with pathological bone remodeling such as the bone
      metastasis of cancer, as well as physiological bone turnover. The pathological
      roles in prostate cancer growth of the two existing types of serum OC, gamma
      carboxylated (GlaOC) and lower- (or un-) carboxylated (GluOC), have not yet been
      discriminatively examined. In the present study, we demonstrate that normal
      prostate epithelial cell growth was promoted by both types of OC, while growth of
      cancer cells in the prostate was accelerated by GlaOC but suppressed by GluOC. We
      suggest that OC regulates prostate cancer growth depending on the gamma
      carboxylation, in part by triggering reduced phosphorylation of receptor tyrosine
      kinases.

PMID- 27698898
TI  - MicroRNA Expression Profile on Solid Subtype of Invasive Lung Adenocarcinoma
      Reveals a Panel of Four miRNAs to Be Associated with Poor Prognosis in Chinese
      Patients.
AB  - According to the reclassification of lung adenocarcinoma (LAC) proposed in 2011,
      solid predominant lung adenocarcinoma (SPA) has been associated with poor
      outcomes for LAC patients. However, the prognostic value of the presence of solid
      subtype remains unclear. Besides, there is little data about the roles of
      microRNA (miRNA) in solid subtype of LAC. In this study, 243 LAC patients were
      classified into solid subtype positive and negative groups (S+ LAC, n=134 and S-
      LAC, n=109) according to whether the solid subtype was more than 5% of the tumor
      component or not. We analyzed the relationship between solid subtype and
      patients' outcome by univariate and multivariate analyses. Solid subtype was
      proved to be significantly associated with the 5-year overall survival and played
      as an independent prognostic factor for stage I-III invasive LAC patients. Then
      miRNA microarray was used to identify differentially expressed miRNAs in solid
      subtype, resulting in 31 differential miRNAs. Quantitative reverse transcription
      PCR (QRT-PCR) was used to validate 4 key miRNAs (miR-133b, miR-155-5p, miR-124
      3p, miR-145-5p). Further, CCK-8 and transwell assays were performed to validate
      the impact of one dysregulated miRNA (miR-133b) on LAC cell function.
      Interestingly, while miR-133b could significantly inhibit the proliferation of
      A549 and SPC-A1, it showed no effect on the migration or invasion of LAC cell
      lines. These results suggest that solid subtype can exert independent prognostic
      impact on LAC patients, and 4 important dysregulated miRNAs in solid subtype of
      LAC may be involved in the malignancy of S+LAC, thus may further have clinical
      perspective for S+ LAC in the future.

PMID- 27698899
TI  - Is mTOR Inhibitor Good Enough for Treatment All Tumors in TSC Patients?
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant and multi-system
      genetic disorder in humans. TSC affects around 25,000 to 40,000 individuals in
      the United States and about 1 to 2 million individuals worldwide, with an
      estimated prevalence of one in 6,000 newborns. TSC occurs in all races and ethnic
      groups, and in both genders. TSC is caused by defects or mutations in two genes,
      TSC1 and TSC2. Loss of TSC1/TSC2 leads to dysregulation of mTOR, resulting in
      aberrant cell differentiation and development, and abnormal enlargement of cells.
      TSC is characterized by the development of benign and/or malignant tumors in
      several organs including renal/liver angiomyolipomas, facial angiofibroma,
      lymphangiomyomatosis, cardiac rhabdomyomas, retinal astrocytic, renal cell
      carcinoma, and brain subependymal giant cell astrocytomas (SEGA). In addition,
      TSC disease causes disabling neurologic disorders, including epilepsy, mental
      retardation and autism. Particularly problematic are the development of renal
      angiomyolipomas, which tend to be larger, bilateral, multifocal and present at a
      younger age compared with sporadic forms. In addition, SEGA block the flow of
      fluid within the brain, causing a buildup of fluid and pressure that leads to
      blurred vision and seizures. In the current review, we describe the pathology of
      TSC disease in key organs and summarize the use of mTOR inhibitors to treat
      tumors in TSC patients.

PMID- 27698900
TI  - Anti-inflammatory and Antitumor Activity of a Triple Therapy for a Colitis
      Related Colorectal Cancer.
AB  - Colorectal cancer (CRC) is an important health issue worldwide, accounting for
      the third place of cancer incidence. Chronic inflammation, as seen in Crohn's
      disease and ulcerative colitis, is the most important risk factor for developing
      CRC, as it favours neoplastic transformation by enhancing epithelial cell
      turnover in the colonic mucosa. Treatments for CRC need to be improved; currently
      they are not specific and have several secondary effects in patients. The main
      objective of this work was to evaluate a new therapeutic strategy against a
      colitis-related colorectal cancer in vivo and in vitro by targeting mTOR
      signaling and lactate dehydrogenase A. Together, these mechanisms directly affect
      tumor energetics. In this study we evaluated a better and more efficient triple
      therapy against a chronic inflammation-associated CRC in vivo and in vitro. After
      the development of tumors, mice were treated intraperitoneally during a forty-day
      period with single drugs or different combinations of Metformin, Sodium Oxamate
      and Doxorubicin. Targeted inhibition of the mTOR pathway, lactate dehydrogenase A
      and the concurrent use of Doxorubicin (called in this work as triple therapy),
      leaded to a notable reduction in the number and size of tumors in mice, and, a
      significant pro-inflammatory cytokines reduction Besides, we showed that treated
      cells were induced to early autophagy, and apoptosis cell death. Our results
      represent a novel and robust therapeutic strategy for overcoming CRC by means of
      targeting central molecular pathways in cancer by the combination of Metformin,
      Oxamate, and Doxorubicin leading to a rapid tumor growth inhibition and a
      dramatic colorectal crypt restoration. Besides, drug combination resulted in a
      notable reduction of anti-inflammatory cytokines.

PMID- 27698901
TI  - High Stoichiometry Phosphorylation of Talin at T144/T150 or S446 Produces
      Contrasting Effects on Calpain-mediated Talin Cleavage and Cell Migration.
AB  - Focal adhesions are large multi-protein complexes that serve as the linkage
      between extracellular matrix (ECM) and actin cytoskeleton and control the network
      of signaling cascades underlying cell migration. Talin plays a key role in focal
      adhesion turnover, and calpain-mediated proteolysis of talin is central to focal
      adhesion disassembly, but its regulation is not well elucidated. Here we
      demonstrate that talin phosphorylation at three high stoichiometry sites on its
      head domain, T144 and T150, or S446, have contrasting effects on calpain-mediated
      cleavage of talin and cell migration by using site-directed mutagenesis to
      inhibit phosphorylation. Expression of talinT144A+T150A stimulated calpain
      mediated cleavage of talin and accelerated focal adhesion disassembly, whereas
      expression of talinS446A fully inhibited talin cleavage by calpain, preventing
      focal adhesion disassembly. A large decrease in phospho-threonine or phospho
      serine levels was seen with talinT144A+T150A or talinS446A respectively, while
      more active ERK was present in talinT144A+T150A than in talinS446A. Cell adhesion
      and transwell assays using uniformly expressing cells showed that expression of
      talinT144A+T150A or talinS446A have opposing effects on cell adhesion and
      migration. These findings define and highlight the integral role of site-specific
      high stoichiometry phosphorylation of talin in regulating calpain-mediated
      cleavage of talin and focal adhesion disassembly, thus controlling adhesion
      stability, cell adhesion and ultimately, cell migration.

PMID- 27698902
TI  - MicroRNA-34c Suppresses Breast Cancer Migration and Invasion by Targeting GIT1.
AB  - Abnormal expression of microRNAs plays important role in tumor metastasis.
      Migration and invasion of cancer cells accord for the metastasis and
      deterioration of breast cancer. However, the regulatory role of microRNAs in the
      invasion and migration of breast cancer cells has not completely understood yet.
      Here we found that microRNA-34c (miR-34c) was significantly downregulated in
      metastatic tissue of breast cancer. In vitro study showed that miR-34c negatively
      regulated GIT1 protein expression by binding to the 3'UTR of GIT1 mRNA.
      Consistently, GIT1 protein expression was found upregulated significantly in
      metastatic breast cancer. Moreover, miR-34c overexpression suppressed the
      expression of GIT1 protein, and this effect was restored by AMO-miR-34c in breast
      cancer cells. Overexpression of miR-34c suppressed cell migration and invasion in
      both MCF-7 and MDA-MD-231 breast cancer cells. Furthermore, knockdown of
      endogenous GIT1 expression reduced the migration and invasion of both two breast
      cancer cells. Collectively, miR-34c downregulation in breast cancer cells
      resulted in the upregulation of GIT1, which in turn enhanced the migration and
      invasion of breast cancer. This study highlights molecular mechanism of migration
      and invasion of breast cancer cells.

PMID- 27698903
TI  - Prognostic Value of Plasma D-dimer in Patients with Resectable Esophageal
      Squamous Cell Carcinoma in China.
AB  - Background: Plasma D-dimer is closely related to prognosis in several cancers.
      The aim of the current study was to determine the prognostic value of plasma D
      dimer in patients with resectable esophageal squamous cell carcinoma (ESCC).
      Methods: A total of 337 patients with resectable ESCC were enrolled in this
      retrospective study. The 5-year cancer-specific survival (CSS) was calculated by
      Kaplan-Meier method. Cox regression analyses were performed to evaluate the
      prognostic factors. A nomogram model was also performed to predict the cancer
      prognosis. Results: In our study, there were 242 patients (71.8%) with plasma D
      dimer <= 0.5 MUg/ml and 95 patients (28.2%) with plasma D-dimer > 0.5 MUg/ml.
      There was a significantly better 5-year CSS in patients with plasma D-dimer <=
      0.5 MUg/ml than patients with plasma D-dimer > 0.5 MUg/ml (35.5% vs. 21.1%, P <
      0.001). Multivariate analyses reported that plasma D-dimer was an independent
      prognostic factor in patients with resectable ESCC (P < 0.001). In addition, a
      nomogram was also performed to predict the CSS. The Harrell's c-index was 0.68.
      Conclusion: We conclude that plasma D-dimer was an independent prognostic
      biomarker in patients with resectable ESCC.

PMID- 27698904
TI  - An Integrated Analysis of the Genome-Wide Profiles of DNA Methylation and mRNA
      Expression Defining the Side Population of a Human Malignant Mesothelioma Cell
      Line.
AB  - Intratumoral heterogeneity is a hallmark of all cancers and functions as the
      major barrier against effective cancer therapy. In contrast to genetic mutations,
      the role of epigenetic modifications in the generation and maintenance of
      heterogeneous cancer cells remains largely undetermined. This study was performed
      to evaluate the epigenetic mechanisms involved in the tumor cell heterogeneity
      using side population (SP) and non-SP cells isolated from a human malignant
      mesothelioma (HMM) cell line. The subpopulations of cancer cells were analyzed by
      methylated DNA immunoprecipitation combined with high-throughput sequencing
      (MeDIP-seq) and RNA-seq methodology. The RNA-seq data were analyzed with the
      MeDIP-seq data in an integrated way to identify the epigenetically modified genes
      that defined the SP. Concomitant changes in mRNA expression and DNA methylation
      were found in 122 genes, including 118 down-regulated genes with hypermethylation
      and 4 up-regulated genes with hypomethylation. Gene ontology revealed that a
      large portion of the genes belonged to the groups of biological processes such as
      stem cell maintenance, stem cell development, stem cell differentiation, and the
      negative regulation of the developmental process. Among these genes, BNC1,
      RPS6KA3, TWSG1 and DUSP15 contained aberrant methylation in the CpG islands of
      the promoter region, indicating that the genes regulated by DNA methylation
      characterized a distinct subpopulation of HMM cells. The present study provided
      valuable information to shed light on the epigenetic contributions to the
      generation and maintenance of tumor cell heterogeneity.

PMID- 27698906
TI  - Lentivirus-mediated Knockdown of HDAC1 Uncovers Its Role in Esophageal Cancer
      Metastasis and Chemosensitivity.
AB  - Histone deacetylationase 1 (HDAC1) is ubiquitously expressed in various cell
      lines and tissues and play an important role of regulation gene expression.
      Overexpression of HDAC1 has been observed in various types of cancers, which
      indicated that it might be a target for cancer therapy. To test HDAC1 inhibition
      for cancer treatment, the gene expression of HDAC1 was knockdown mediated by a
      lentivirus system. Our data showed the gene expression of HDAC1 could be
      efficiently knockdown by RNAi mediated by lentivirus in esophageal carcinoma
      EC109 cells. Knockdown of HDAC1 led to significant decrease of cell growth and
      altered cell cycle distribution. The result of transwell assay showed that the
      numbers of cells travelled through the micropore membrane was significantly
      decreased as HDAC1 expression was knockdown. Moreover, HDAC1 knockdown inhibited
      the migration of EC109 cells as determining by scratch test. Additionally,
      enhancement of cisplatin-stimulated apoptosis was detected by HDAC1 knockdown.
      Our data suggested inhibition of HDAC1 expression by lentivirus mediated shRNA
      might be further applied for esophageal cancer chemotherapy.

PMID- 27698907
TI  - Sample Level Enrichment Analysis of KEGG Pathways Identifies Clinically Relevant
      Subtypes of Glioblastoma.
AB  - Background: Glioblastoma is the most lethal primary brain tumor in adults.
      Aberrant signal transduction pathways, associated with the progression of
      glioblastoma, have been identified recently and may offer a potential gene
      therapy strategy. Methods and Findings: We first used the sample level enrichment
      analysis to transfer gene expression profile of TCGA dataset into pathway
      enrichment z-score matrix. Then, we classified glioblastoma into five subtypes
      (Cluster A to Cluster E) by the consensus clustering and silhouette analysis.
      Principle component analysis showed the five subtype could be separated by first
      three principle components. Integrative omics data showed that mesenchymal
      subtype was rich in Cluster A, neural subtype was centered in Cluster D and
      proneural subtype was gathered in Cluster E, while Cluster E showed a high
      percentage of G-CIMP subtype. Additionally, according to analyze the overall
      survival and progression free survival of each subtype by Kaplan-Merie analysis
      and Cox hazard proportion model, we identified Cluster D and Cluster E received a
      better prognosis. Conclusions: We report a clinically relevant classification of
      glioblastoma based on sample level KEGG pathway enrichment profile and this novel
      classification system provided new insights into the heterogeneity of
      glioblastoma, and may be used as an important clinical tool to predict the
      prognosis.

PMID- 27698908
TI  - Factors Influencing Clinicians' Choice of Adjuvant S-1 versus Capecitabine plus
      Oxaliplatin after Curative Gastrectomy in Patients with Gastric Cancer.
AB  - Purpose: Two recent randomized, phase III trials in Asia (ACTS-GC and CLASSIC)
      documented the survival benefit of postoperative chemotherapy after D2 lymph node
      dissection in patients with gastric cancer. We sought to determine what factors
      influenced clinicians' choices of either S-1 or capecitabine plus oxaliplatin
      (CAPOX) as adjuvant therapy after curative D2 gastrectomy. Materials and Methods:
      We retrospectively reviewed the clinicopathologic factors and adjuvant treatments
      for 435 patients from nine centers in Korea who were treated with either S-1 or
      CAPOX adjuvant chemotherapy after undergoing curative D2 gastrectomy between
      January 2013 and July 2014. Results: Of the 435 patients, 204 (46.9%) were
      treated with S-1 and 231 (53.1%) were treated with CAPOX. The median age at
      diagnosis was 61 years (range, 30-88). CAPOX was prescribed more often for
      patients who were 65 years of age or younger than for patients who were age 65 or
      older (77.1% vs. 22.9%, P<0.0001). Of the patients in stage II, 121 (60.8%) were
      treated with S-1 and 78 (39.2%) were given CAPOX; however, of those in stage III,
      83 (35.2%) received S-1 and 153 (64.8%) were treated with CAPOX (P<0.0001).
      Conclusions: Clinicians only preferred CAPOX for younger patients with stage III
      gastric cancer after curative D2 gastrectomy. However, for elderly patients,
      clinicians more chose S-1 regardless of the stage.

PMID- 27698905
TI  - GSTT1 Null Genotype Significantly Increases the Susceptibility to Urinary System
      Cancer: Evidences from 63,876 Subjects.
AB  - GSTT1 gene plays an important role in detoxification and clearance of reactive
      oxygen species(ROS). A null variant in this gene has been demonstrated to confer
      cancer susceptibility. Although many studies have demonstrated the association
      between GSTT1 null polymorphism and urinary system cancer susceptibility, several
      publications reported opposite conclusions. For better understanding the effects
      of this polymorphism on the risk of urinary system cancer, a updated meta
      analysis was performed with a total of 26,666 cases and 37,210 controls extracted
      from 117 studies, by following the latest meta-analysis guidelines (PRISMA). The
      results suggested that the GSTT1 null genotype was significantly associated with
      an increased risk of urinary system cancer (OR=1.13, 95%CI=1.05-1.22).
      Furthermore, stratified analyses by the type of cancer, ethnicity, source of
      control and quality score presented a significantly increased risk associated
      with GSTT1 null genotype in bladder and prostate cancer subgroup, Caucasians and
      Indians subgroup, population-based(PB) subgroup, medium quality and low quality
      subgroup. Overall, our meta-analysis suggested that GSTT1 null genotype is a
      potential cancer susceptibility variant. Well-designed and large-cohort studies
      are needed to confirm the association between GSTT1 null genotype and urinary
      system cancer risk.

PMID- 27698909
TI  - Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients
      with Nasopharyngeal Carcinoma.
AB  - Background: Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting
      enzyme involving in the production of gamma-aminobutyric acid (GABA), exists in
      the GABAergic neurons in the central nervous system (CNS). Little is known about
      the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a
      data set derived from a published transcriptome database, this study first
      identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate
      GAD1 expression and its prognostic effect on patients with early and
      locoregionally advanced NPC. Methods: We evaluated GAD1 immunohistochemistry and
      performed an H-score analysis on biopsy specimens from 124 patients with
      nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H
      score higher than the median value. The findings of such an analysis are
      correlated with clinicopathological behaviors and survival rates, namely disease
      specific survival (DSS), distant-metastasis-free survival (DMeFS), and local
      recurrence-free survival (LRFS) rates. Results: GAD1 overexpression was
      significantly associated with an increase in the primary tumor status (p < 0.001)
      and American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.002) and was a
      univariate predictor of adverse outcomes of DSS (p = 0.002), DMeFS (p < 0.0001),
      and LRFS (p = 0.001). In the multivariate comparison, in addition to advanced
      AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of
      short DSS (p = 0.004, hazard ratio = 2.234), DMeFS (p < 0.001, hazard ratio =
      4.218), and LRFS (p = 0.013, hazard ratio = 2.441) rates. Conclusions: Our data
      reveal that GAD1 overexpression was correlated with advanced disease status and
      may thus be a critical prognostic indicator of poor outcomes in NPC and a
      potential therapeutic target to facilitate the development of effective treatment
      modalities.

PMID- 27698910
TI  - Increased Prevalence of Esophageal Cancer in Areas with High Levels of Nickel in
      Farm Soils.
AB  - Background: Heavy metal pollution in farm soils is a grave concern in Taiwan.
      Previously, we found the incidence of oral cancer (OC) correlated positively with
      levels of nickel and arsenic in farm soils. Many OC patients have a second
      malignancy, among which esophageal cancer (EC) is the most common one in Taiwan.
      Objectives: We aimed to investigate whether these two cancers share some common
      risk factors. Methods: Taiwan began a compulsory national health insurance
      program in 1995. We used a database from this program to calculate the prevalence
      of EC and OC in Taiwan. We compared the prevalence of EC with prevalence of betel
      nut chewers in adults and the information of heavy metal in farm soils to look
      for any association. Results: The prevalence of OC and prevalence of EC were
      strongly correlated. The prevalence of betel nut chewing correlated with OC
      prevalence, but not with EC prevalence. An increased prevalence (1.9 fold) of EC
      was found where the farm soils contained high levels of nickel. Meanwhile, among
      the eight heavy metals studied, only the levels of nickel in the farm soils
      correlated statistically with the prevalence of EC. Conclusion: Nickel is
      probably a common environmental risk factor for esophageal cancer and oral
      cancer.

PMID- 27698911
TI  - XPG Gene Polymorphisms Contribute to Colorectal Cancer Susceptibility: A Two
      Stage Case-Control Study.
AB  - Previous studies have reported that xeroderma pigmentosum group G (XPG) gene
      polymorphisms may modulate colorectal cancer (CRC) susceptibility. In this study,
      we performed a two-stage case-control study to comprehensively investigate the
      associations of five polymorphisms in the XPG gene with CRC risk in 1,901 cases
      and 1,976 controls from Southern China, including rs2094258 C>T, rs751402 C>T,
      rs2296147 T>C, rs1047768 T>C and rs873601 G>A. After combining data from two
      stages, we found that three of the studied polymorphisms (rs2094258 C>T, rs751402
      C>T, and rs873601 G>A) were significantly associated with CRC susceptibility.
      After adjustment for age and gender, multivariate logistic regression analysis
      indicated that carriers of the rs2094258 T alleles had an increased CRC risk [CT
      vs. CC: adjusted odds ratio (OR)=1.17, 95% confidence interval (CI)=1.01-1.36; TT
      vs. CC: adjusted OR=1.49, 95% CI=1.18-1.89; TT vs. CT/CC: adjusted OR=1.38, 95%
      CI=1.10-1.72]. Likely, rs873601 A allele also conferred increased CRC
      susceptibility. In contrast, a protective association was identified between
      rs751402 C>T polymorphism and the risk of CRC. In summary, our results indicated
      that these three polymorphisms were found to associate with CRC susceptibility in
      a Southern Chinese population.

PMID- 27698912
TI  - MiR-193a-5p Targets the Coding Region of AP-2alpha mRNA and Induces Cisplatin
      Resistance in Bladder Cancers.
AB  - Transcription factor AP-2 alpha (AP-2alpha or TFAP2A) is a newly identified
      prognostic marker of chemotherapy; its expression is positively correlated with
      chemosensitivity and survival of cancer patients. Using computational programs,
      we predicted that the coding region of AP-2alpha gene contains a potential miRNA
      response element (MRE) of miR-193a-5p, and the single nucleotide polymorphism
      (SNP) site (c.497A>G, rs111681798) resides within the predicted MRE. The results
      of luciferase assays and Western blot analysis demonstrated that miR-193a-5p
      negatively regulated the expression of AP-2alpha proteins, but have no influence
      on the mutant AP-2alpha (c.497A>G). Infection with lentiviral AP-2alpha gene or
      miR-193a-5p inhibitor in the bladder cancer cells decreased migration and
      cisplatin resistance, while knockdown of AP-2alpha gene or overexpression of miR
      193a-5p in the urothelial cell line SV-HUC-1 increased migration and cisplatin
      resistances. We concluded that miR-193a-5p induced cisplatin resistance by
      repressing AP-2alpha expression in bladder cancer cells.

PMID- 27698913
TI  - Pretreatment TG/HDL-C Ratio Is Superior to Triacylglycerol Level as an
      Independent Prognostic Factor for the Survival of Triple Negative Breast Cancer
      Patients.
AB  - PURPOSE: Previous studies have reported that the triacylglycerol (TG) level and
      high-density lipoprotein cholesterol (HDL-C) are connected with breast cancer.
      However, the prognostic utility of the TG level and the TG/HDL-C ratio (THR) as
      conventional biomarkers in patients with triple negative breast cancer (TNBC) has
      not been elucidated. In this research, we investigate and compare the predictive
      value of the pretreatment serum TG level and THR in TNBC patients. METHODS: We
      evaluated 221 patients with TNBC who had pretreatment conventional blood
      biochemical examinations and calculated the THR. Univariate and multivariate
      logistic regression analyses were used to assess the effect of the TG level and
      the THR on overall survival (OS) and disease-free survival (DFS). RESULTS: The
      optimal cutoff values of the TG level and the THR were determined to be 0.935
      mmol/L and 0.600, respectively. As shown in a Kaplan-Meier analysis, TNBC
      patients with a high TG level and THR had shorter OS and DFS than patients in the
      low-level groups (p < 0.05). The multivariate analysis suggested that the
      pretreatment THR level is an independent prognostic factor of OS (HR: 1.935;
      95%CI: 1.032-3.629; p = 0.040) in TNBC patients. CONCLUSIONS: In conclusion, our
      data indicate that a high THR is an independent predictor and is superior to the
      TG level for predicting poor clinical outcomes in TNBC patients.

PMID- 27698914
TI  - Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid
      Phenethyl Ester by gamma Cyclodextrin.
AB  - Caffeic Acid Phenethyl Ester (CAPE) is a key component in New Zealand propolis,
      known for a variety of health promoting and therapeutic potentials. We
      investigated the molecular mechanism of anticancer and anti-metastasis activities
      of CAPE. cDNA array performed on the control and CAPE-treated breast cancer cells
      revealed activation of DNA damage signaling involving upregulation of GADD45alpha
      and p53 tumor suppressor proteins. Molecular docking analysis revealed that CAPE
      is capable of disrupting mortalin-p53 complexes. We provide experimental evidence
      and demonstrate that CAPE induced disruption of mortalin-p53 complexes led to
      nuclear translocation and activation of p53 resulting in growth arrest in cancer
      cells. Furthermore, CAPE-treated cells exhibited downregulation of mortalin and
      several other key regulators of cell migration accountable for its anti
      metastasis activity. Of note, we found that whereas CAPE was unstable in the
      culture medium (as it gets degraded into caffeic acid by secreted esterases), its
      complex with gamma cyclodextrin (gammaCD) showed high efficacy in anti-tumor and
      anti-metastasis assays in vitro and in vivo (when administered through either
      intraperitoneal or oral route). The data proposes that CAPE-gammaCD complex is a
      potent anti-cancer and anti-metastasis reagent.

PMID- 27698915
TI  - Preoperative Lymphocyte-Monocyte Ratio Is a Predictor of Suboptimal Cytoreduction
      in Stage III-IV Epithelial Ovarian Cancer.
AB  - OBJECTIVE: To determine whether the preoperative lymphocyte-monocyte ratio (LMR)
      is a predictor of suboptimal cytoreduction in advanced-stage epithelial ovarian
      cancer (EOC). METHODS: Preoperative clinico-pathologic and hematologic parameters
      were reviewed in a total of 154 patients with EOC submitted to primary
      cytoreductive surgery. Patients were categorized into two different groups
      according to the results of cytoreductive surgery: optimal and suboptimal
      cytoreduction. Continuous variables were categorized into two groups using the
      best cutoff points selected on the receiver operating characteristic (ROC) curve
      for suboptimal cytoreduction. RESULTS: Based on data collected from the 154
      patients, 133 (86.4%) and 21 (13.6%) patients presented with stage III and IV
      disease, respectively. One hundred seventeen (76.0%) patients had serous
      adenocarcinoma, and 92 (59.7%) had histologic tumor grade 3. The optimal and
      suboptimal cytoreduction groups included 96 (62.3%) and 58 patients (37.7%),
      respectively. The best LMR cutoff point for suboptimal cytoreduction was 3.75. On
      multivariate logistic regression analysis, age, cancer antigen 125, white blood
      cell count, and LMR were found to be the strongest predictors for suboptimal
      cytoreduction (P=0.0037, 0.0249, 0.0062, and 0.0015, respectively). Conclusion:
      Preoperative LMR is an independent predictor of suboptimal cytoreduction. It
      provides additional prognostic information beyond the biological parameters of
      the tumor.

PMID- 27698916
TI  - Diet- and Genetically-induced Obesity Produces Alterations in the Microbiome,
      Inflammation and Wnt Pathway in the Intestine of Apc+/1638N Mice: Comparisons and
      Contrasts.
AB  - Obesity is an established risk factor for colorectal cancer (CRC). Our previous
      study indicated that obesity increases activity of the pro-tumorigenic Wnt
      signaling. Presently, we sought to further advance our understanding of the
      mechanisms by which obesity promotes CRC by examining associations between
      microbiome, inflammation and Wnt-signaling in Apc+/1638N mice whose obesity was
      induced by one of two modalities, diet- or genetically-induced obesity. Three
      groups were employed: Apc+/1638NLepr+/+ fed a low fat diet (10% fat),
      Apc+/1638NLepr+/+ fed a high fat diet (60% fat, diet-induced obesity), and
      Apc+/1638NLeprdb/db fed a low fat diet (genetically-induced obesity). All animals
      received diets for 16 weeks from 8 to 24 weeks of age. The abundance of 19 bowel
      cancer-associated bacterial taxa were examined by real-time PCR. The abundance of
      Turicibacter and Desulfovibrio decreased, but F. prausnitizii increased, in diet
      induced obese mice (p < 0.05). In contrast, in genetically-induced obese mice,
      Bifidobacterium, A. muciniphila and E. rectale decreased, but Peptostrptococcus,
      and E. coli increased (p < 0.05). Both diet- and genetically-induced obesity
      altered the expression of genes involved in bacterial recognition (MyD88) and
      increased inflammation as indicated by elevated levels of cytokines (IFNgamma and
      TNF-alpha for genetically-induced obesity, and IL-6 for diet-induced obesity).
      The elevated inflammation was associated with altered expression of genes that
      are integral components of the Wnt-signaling cascade in a fashion indicating its
      activation. These findings demonstrate that the composition of the small
      intestinal microbiome is affected differently in diet- and genetically-induced
      obesity, but both are associated with elevated intestinal inflammation and
      alterations of the Wnt pathway towards enhancing tumorigenesis.

PMID- 27698917
TI  - Noninvasive Monitoring of Glioma Growth in the Mouse.
AB  - Malignant gliomas are the most common and deadly primary malignant brain tumors.
      In vivo orthotopic models could doubtless represent an appropriate tool to test
      novel treatment for gliomas. However, methods commonly used to monitor the growth
      of glioma inside the mouse brain are time consuming and invasive. We tested the
      reliability of a minimally invasive procedure, based on a secreted luciferase
      (Gaussia luciferase), to frequently monitor the changes of glioma size. Gluc
      activity was evaluated from blood samples collected from the tail tip of mice
      twice a week, allowing to make a growth curve for the tumors. We validated the
      correlation between Gluc activity and tumor size by analysing the tumor after
      brain dissection. We found that this method is reliable for monitoring human
      glioma transplanted in immunodeficient mice, but it has strong limitation in
      immunocompetent models, where an immune response against the luciferase is
      developed during the first weeks after transplant.

PMID- 27698919
TI  - Transketolase Serves a Poor Prognosticator in Esophageal Cancer by Promoting Cell
      Invasion via Epithelial-Mesenchymal Transition.
AB  - Background: To characterize the potential function and clinical significance of
      Transketolase (TKT) in esophageal cancer. Methods: High invasive esophageal
      squamous cell carcinoma (ESCC) cell line CE48T/VGH was used. Cellular functions
      in response to TKT modulation were examined, including cell growth, migration and
      invasion. The underlying molecules involved in the TKT regulatory mechanism were
      determined by western blot and confocal microscopic analysis. Clinically, TKT
      expressions in 76 ESCC patients were assessed by immunohistochemical (IHC)
      method, and the association with treatment outcome was determined. Results: TKT
      silencing inhibited cell migration and invasion but had a minimal effect on cell
      growth. This TKT silencing also induced the reversion of epithelial-mesenchymal
      transition (EMT), as evidenced by the spindle to cuboidal morphological change,
      increased the expression of epithelial markers (gamma-catenin), and decreased the
      levels of mesenchymal markers (fibronectin and N-cadherin). Mechanically, TKT was
      shown to modulate the EMT through the pERK-Slug/Snail-associated signaling
      pathway. Clinically, a high level of TKT in the cancer tissues of patients with
      esophageal squamous cell carcinoma was associated with poor survival (P = 0.042).
      In the multivariate analysis, a high TKT level was also shown to be an
      independent unfavorable prognostic factor (Odds ratio: 1.827, 95% confidence
      interval: 1.045-3.196, P = 0.035). Conclusions: TKT contributes to esophageal
      cancer by promoting cell invasion via meditating EMT process. Clinically, the
      over-expression of TKT in ESCC patients predicts poorer survival. TKT inhibition
      may be a useful strategy to intervene in cancer cell invasion and metastasis,
      which may lead to better prognosis for ESCC patients.

PMID- 27698920
TI  - Total PC Activity Is Increased in Uterine Lavage of Post-Menopausal Endometrial
      but Not Ovarian Cancer Patients.
AB  - Endometrial and ovarian cancers are two most common cancers affecting women in
      their post-menopausal years. To date, there are no simple biochemical tests to
      detect these cancers at early stages. Our previous study has demonstrated that
      the activity of total proprotein convertases (PCs) is significantly increased in
      uterine lavage at all stages of endometrial cancer, suggesting uterine lavage
      which can be obtained relatively non-invasively may provide a simple tool for the
      detection of endometrial cancer. However, uterine lavage may also contain ovarian
      derived factors, and PCs are also reported to be up-regulated in ovarian cancer.
      In this study we determined whether increases in uterine lavage PC activity are
      specific to endometrial cancer or are also associated with ovarian cancer. PC
      activity was detected in all uterine lavages examined but no difference was found
      between women with and without ovarian cancer. On the other hand, the PC activity
      was significantly higher in post-menopausal endometrial cancer patients,
      consistent with our previous report. These results suggest that measuring total
      PC activity in uterine lavage is a useful tool to detect endometrial cancer
      specifically.

PMID- 27698918
TI  - Plasma Circulating Cell-free DNA Integrity as a Promising Biomarker for Diagnosis
      and Surveillance in Patients with Hepatocellular Carcinoma.
AB  - The clinical significance of circulating cell-free DNA (cfDNA) integrity as
      diagnostic and surveillance biomarker in hepatocellular carcinoma (HCC) was
      investigated and compared to that of alpha fetoprotein (AFP). Liver cancer
      patients had lower cfDNA integrity than those with benign diseases (P = 0.0167)
      and healthy individuals (P = 0.0025). Patients with HCC and non-HCC liver cancers
      (P = 0.7356), and patients with benign diseases and healthy individuals (P =
      0.9138) had comparable cfDNA integrity respectively. cfDNA integrity increased
      after hepatectomy in cancer patients (P = 0.0003). The AUCs for detecting HCC by
      cfDNA integrity and AFP were 0.705 (P = 0.005) and 0.605 (P = 0.156),
      respectively. We found cfDNA integrity decreased in HCC patients and has the
      potential as promising biomarker for HCC diagnosis and treatment surveillance.

PMID- 27698922
TI  - Potential Function of Exogenous Vimentin on the Activation of Wnt Signaling
      Pathway in Cancer Cells.
AB  - Cancer cell signaling, growth, morphology, proliferation and tumorigenic
      potential are largely depending on the signaling molecules present naturally in
      the tumor microenvironment and the identification of key molecules that drive the
      tumor progression is critical for the development of new modalities for the
      prevention of tumor progression. High concentrations of vimentin in the blood of
      cancer patients have been reported, however the function of blood circulating
      vimentin remains unknown. Here, we investigated the functional role of
      exogenously supplemented vimentin on colon cancer cells and examined the Wnt
      Signaling activation and cancer cell invasion. Vimentin when supplemented to the
      cancer cells remained bound to the surface of the cancer cells. Furthermore,
      bound vimentin activates Wnt signaling pathway as detectable by increased beta
      catenin accumulation in the nucleus with concomitant activation of beta-catenin
      dependent transcription of Wnt signaling downstream targets. Functionally, there
      was an increase in the rate of cellular invasion in these cancer cells upon
      binding with vimentin. Our results thus suggest that free vimentin in the tumor
      microenvironment acts as a positive regulator of the beta-catenin signaling
      pathway, thus providing a basis for cancer invasive properties.

PMID- 27698921
TI  - Interleukin-6 from Ovarian Mesenchymal Stem Cells Promotes Proliferation, Sphere
      and Colony Formation and Tumorigenesis of an Ovarian Cancer Cell Line SKOV3.
AB  - The origin of the majority of epithelial ovarian cancers (EOC) is regarded as
      extraovarian, with the ovary being the secondary site. The aim of this study was
      to explore the possible role of ovarian mesenchymal stem cells (OvMSCs) and
      secreted IL-6 in the development of EOC. OvMSCs were derived from normal ovarian
      stroma. Cell surface markers and differentiation capability were determined. The
      effects of IL-6 and conditioned medium of OvMSCs on the malignant phenotype of
      SKOV3 ovarian cancer cells were tested, and the status of STAT3 and ERK
      phosphorylation was investigated. OvMSCs had similar surface marker profiles as
      bone marrow mesenchymal stem cells, i.e., CD44 (+), CD90 (+) and CD45 (-), and
      was readily inducible to osteogenic, adipogenic and chondrogenic differentiation.
      OvMSCs secreted an extremely high level (>2500 pg/ml) of IL-6. Treatment of SKOV3
      cells with conditioned media from OvMSCs increased cell proliferation, tumor
      sphere formation and anchorage independent growth, and resulted in activation of
      STAT3 but not ERK. Coinjection of OvMSCs with SKOV3 cell enhanced tumorigenesis
      in NOD-SCID mice. All of these behaviors were blocked by IL-6 receptor blocking
      antibody administered in vitro or in vivo. The OvMSCs alone injected into mice
      had no tumor growth after 3 months. By secreting high levels of IL-6, OvMSCs
      enhance the proliferation, sphere and colony formation and tumorigenesis of SKOV3
      cells.

PMID- 27698923
TI  - Validation and Comparison of the 7th Edition of the American Joint Committee on
      Cancer Staging System and Other Prognostic Models to Predict Relapse-Free
      Survival in Asian Patients with Parotid Cancer.
AB  - Purpose: Parotid cancer is a rare malignancy characterized by a heterogeneous
      histologic subtype and distinct biologic behavior. The present study aimed to
      externally validate and compare the performances of the American Joint Committee
      on Cancer (AJCC) staging system (7th Edition), Carrillo score, and Vander Poorten
      score in the prediction of tumor relapse probability in a large cohort of Asian
      parotid cancer patients. Methods: In total, 261 patients who underwent primary
      surgery for localized parotid cancer between 2002 and 2014 at the four affiliated
      hospitals of Chang Gung Memorial Hospital were identified. All patients were
      categorized into different prognostic groups defined by these three models for
      the comparison of associated relapse-free survival (RFS) rates. Results: The 5
      year overall survival, cancer-specific survival, and RFS rates were 82.9%, 86.2%,
      and 77.5%, respectively. All three models were significantly powerful in
      discriminating between the tumors of patients in the lowest and highest risk
      groups. The c-statistic for predicting the 5-year RFS was 0.74 for the AJCC
      staging, 0.74 for the Vander Poorten score, and 0.62 for the Carrillo score. The
      AJCC staging and Vander Poorten score gave significantly high c-statistic values
      compared to the Carrillo score. Conclusion: Our data validated that all three
      models are significantly powerful in discriminating tumor relapse between
      patients in lowest and highest risk groups. The AJCC system and Vander Poorten
      score proved superior to the Carrillo score, and showed similar performances in
      discriminating between the 5-year RFS probabilities of low and high-risk Asian
      parotid cancer patients.

PMID- 27698925
TI  - Low Proteolytic Clipping of Histone H3 in Cervical Cancer.
AB  - Chromatin in cervical cancer (CC) undergoes chemical and structural changes that
      alter the expression pattern of genes. Recently, a potential mechanism, which
      regulates gene expression at transcriptional levels is the proteolytic clipping
      of histone H3. However, until now this process in CC has not been reported. Using
      HeLa cells as a model of CC and human samples from patients with CC, we identify
      that the H3 cleavage was lower in CC compared with control tissue. Additionally,
      the histone H3 clipping was performed by serine and aspartyl proteases in HeLa
      cells. These results suggest that histone H3 clipping operates as part of post
      translational modification system in CC.

PMID- 27698926
TI  - FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Cancer: A Single Centre
      Cohort Study.
AB  - Introduction: FOLFIRINOX is emerging as new standard of care for fit patients
      with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer
      (MPC). However, some of the physicians are reluctant to use FOLFIRINOX due to
      high toxicity rates reported in earlier studies. We reviewed our experience with
      FOLFIRINOX in LAPC and MPC, focussing on dose adjustments, toxicity and efficacy.
      Methods: We reviewed all patients with LAPC or MPC treated with FOLFIRINOX in our
      institution between April 2011 and December 2015. Unresectability (stage III and
      IV) was determined by the institution's multidisciplinary team for pancreatic
      cancer. Results: Fifty patients (18 LAPC and 32 MPC) were enrolled, with a median
      age of 55 years (IQR 49-66) and WHO performance status of 0/1. FOLFIRINOX was
      given as first-line treatment in 82% of patients. Dose modifications were applied
      in 90% of patients. The median number of completed cycles was 8 (IQR 5-9). Grade
      3-4 toxicity occurred in 52% and grade 5 toxicity in 2%. The response rate was
      25% (12% in LAPC, 32% in MPC). Median overall survival and progression-free
      survival were 14.8 and 10.3 months in LAPC, and 9.0 and 5.9 months in MPC,
      respectively. Overall 1- and 2-year survival was 65% and 10% in LAPC and 40% and
      5% in MPC. Within the LAPC group, 6 patients (33%) underwent local ablative
      therapy and 1 patient (6%) a resection, leading to a median survival of 21.8
      months. Conclusion: FOLFIRINOX treatment with nearly routine dose modification
      was associated with acceptable toxicity rates, relatively high response rates and
      an encouraging overall survival.

PMID- 27698927
TI  - Senescence Process in Primary Wilms' Tumor Cell Culture Induced by p53
      Independent p21 Expression.
AB  - : Wilms tumor (WT) is an embryonal tumor occurring in developing kidney tissue.
      WT cells showing invasive cancer characteristics, also retain renal stem cell
      behaviours. In-vitro culture of WT is hampered by limited replicative potential.
      This study aimed to establish a longterm culture of WT cells to enable the study
      of molecular events to attempt to explain its cellular senescence. METHODS:
      Primary cell cultures from fresh WT tumor specimen were established. Of 5
      cultures tried, only 1 could be propagated for more than 7 passages. One culture,
      identified as PSU-SK-1, could be maintained > 35 passages and was then subjected
      to molecular characterization and evaluation for cancer characteristics. The
      cells consistently harbored concomitant mutations of CTNNB1 (Ser45Pro) and WT1
      (Arg413Stop) thorough the cultivation. On Transwell invasion assays, the cells
      exhibited migration and invasion at 55% and 27% capability of the lung cancer
      cells, A549. On gelatin zymography, PSU-SK-1 showed high expression of the matrix
      metaloproteinase. The cells exhibited continuous proliferation with 24-hour
      doubling time until passages 28-30 when the growth slowed, showing increased cell
      size, retention of cells in G1/S proportion and positive beta-galactosidase
      staining. As with those evidence of senescence in advanced cell passages,
      expression of p21 and cyclin D1 increased when the expression of beta-catenin and
      its downstream protein, TCF, declined. There was also loss-of-expression of p53
      in this cell line. In conclusion, cellular senescence was responsible for limited
      proliferation in the primary culture of WT, which was also associated with
      increased expression of p21 and was independent of p53 expression. Decreased
      activation of the Wnt signalling might explain the induction of p21 expression.

PMID- 27698928
TI  - Phenylethanoid Glycosides from Cistanche tubulosa Inhibits the Growth of B16-F10
      Cells both in Vitro and in Vivo by Induction of Apoptosis via Mitochondria
      dependent Pathway.
AB  - Cistanche tubulosa phenylethanoid glycosides (CTPG) have been shown various
      biological activities including anti-allergy, hepatoprotective activity and bone
      regeneration. However, the anti-tumor activity of CTPG needs to be investigated.
      CTPG was used to treat B16-F10 cells both in vitro and in vivo. We found that
      CTPG dramatically changed the morphology of B16-F10 cells, and significantly
      reduced the viability of B16-F10 cells in a dose-dependent and time-dependent
      manner, which might be mediated by CTPG-induced apoptosis and cell cycle arrest.
      After CTPG treatment, the expressions of BAX and BCL-2 were up-regulated and down
      regulated, respectively. Moreover, mitochondrial membrane potential was reduced
      and ROS generation was increased. Consequently, the levels of cytochrome c and
      cleaved-caspase-3 and -9 were up-regulated by CTPG treatment but not for cleaved
      caspase-8. We further observed that CTPG significantly inhibited the tumor growth
      in vivo and improved the survival rate of tumor mice. We also observed that CTPG
      promoted the proliferation of splenocytes and increased the proportions of CD4+
      and CD8+ T cells in spleens of tumor mice. The results showed that CTPG induced
      the apoptosis of B16-F10 cells through mitochondria-dependent pathway, suggesting
      that CTPG could be a potential candidate for treatment of cancer.

PMID- 27698924
TI  - Long Non-coding RNAs in Urologic Malignancies: Functional Roles and Clinical
      Translation.
AB  - Early diagnosis and surveillance for metastasis and recurrences are critical
      issues of urologic cancer. Deregulation of long non-coding RNAs (lncRNAs) has
      been implicated in urologic malignancies and represents potential markers or
      therapeutic targets. However, the utility of lncRNA as biomarkers appears to be
      overstated due to heterogeneous or irreproducible results from different studies.
      Thus, a critical and cautious review on the biomarker potential of lncRNAs is
      needed. This review provides an update on new findings of lncRNA-based markers
      for urologic cancer. The diverse mechanisms and associated examples of lncRNAs
      involved during the carcinogenesis of prostate cancer, bladder cancer and renal
      cancer were discussed in a more balanced and critical manner, as were the
      suitability of lncRNAs as diagnostic or prognostics markers.

PMID- 27698929
TI  - ENaC/DEG in Tumor Development and Progression.
AB  - The epithelial Na+ channel/degenerin (ENaC/DEG) superfamily, including the acid
      sensing ion channels (ASICs), is characterized by a high degree of similarity in
      structure but highly diverse in physiological functions. These ion channels have
      been shown to be important in several physiological functions of normal
      epithelial cells, including salt homeostasis, fluid transportation and cell
      mobility. There is increasing evidence suggesting that ENaC/DEG channels are
      critically engaged in cancer cell biology, such as proliferation, migration,
      invasion and apoptosis, playing a role in tumor development and progression. In
      this review, we will discuss recent studies showing the role of ENaC and ASIC
      channels in epithelial cells and its relationship to the oncogenesis.

PMID- 27698930
TI  - Statins Dose-Dependently Exert Significant Chemopreventive Effects Against
      Various Cancers in Chronic Obstructive Pulmonary Disease Patients: A Population
      Based Cohort Study.
AB  - PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with an
      increased cancer risk. We evaluated the chemopreventive effect of statins against
      all cancers in COPD patients and identified the statin with the strongest
      chemopreventive effect. PATIENTS AND METHODS: All patients diagnosed with COPD at
      health care facilities in Taiwan (n = 116,017) from January 1, 2001, to December
      31, 2012, were recruited. Each patient was followed to assess the following
      protective and risk factors for all cancers: age; sex; comorbidities (diabetes,
      hypertension, dyslipidemia) and the Charlson comorbidity index [CCI]);
      urbanization level; monthly income; and nonstatin drug use. The index date of
      statins use was the date of COPD confirmation. Propensity scores (PSs) were
      derived using a logistic regression model to estimate the effect of statins by
      considering the covariates predicting intervention (statins) receipt. To examine
      the dose-response relationship, we categorized statin use into four groups in
      each cohort (<28 [statin nonusers], 28-90, 91-365, and >365 cumulative defined
      daily dose). RESULTS: After PS adjustment for age, sex, CCI, diabetes,
      hypertension, dyslipidemia, urbanization level, and monthly income, we analyzed
      the all-cancer risk. The adjusted hazard ratios (aHRs) for the all-cancer risk
      were lower among statin users than among statin nonusers (aHR = 0.46, 95%
      confidence interval: 0.43 to 0.50). The aHRs for the all-cancer risk were lower
      among patients using rosuvastatin, simvastatin, atorvastatin, pravastatin, and
      fluvastatin than among statin nonusers (aHRs = 0.42, 0.55, 0.59, 0.66, and 0.78,
      respectively). Sensitivity analysis indicated that statins dose-dependently
      reduced the all-cancer risk. CONCLUSION: Statins dose-dependently exert a
      significant chemopreventive effect against various cancers in COPD patients. In
      particular, rosuvastatin has the strongest chemopreventive effect.

PMID- 27698931
TI  - The Efficacy of Bevacizumab in Different Line Chemotherapy for Chinese Patients
      with Metastatic Colorectal Cancer.
AB  - Objective: To evaluate the effect of bevacizumab in different lines for Chinese
      patients with metastatic colorectal cancer (mCRC). Methods: Patients of mCRC
      treated with bevacizumab or not at Sun Yat-sen University Cancer Center from 2007
      to 2013 were recruited as study and control group. Endpoints were overall
      survival (OS), progression free survival (PFS), objective response rate (ORR) and
      disease control rate (DCR). Corresponding survival rates of first- and second
      line in study and control group were compared. Results: 1. Median OS of study and
      control group were 44.8 (95% CI: 37.1~52.4) months, 36.1 (95% CI: 32.8~39.5)
      months respectively, which were significantly different (P=0.004). 2. In the
      first line treatment, median OS of study and control group were 49.9(95% CI:
      40.1~59.8) months and 36.1 (95% CI: 32.7~39.4) months (P=0.002), respectively.
      And median PFS were 10.1(95% CI: 8.7~11.5) months and 6.2 (95% CI: 5.5~6.8)
      months (P<0.001), respectively. 3. In the second line treatment, median OS of
      study and control group were 34.8 (95% CI: 26.3~43.3) months and 24.6 (95% CI:
      22.2~27.0) months (P=0.022), respectively. And the mPFS were 6.3 (95% CI:
      4.7~7.8) months and 3.1 (95% CI: 2.5~3.6) months (P<0.001), respectively. 4.
      Median OS of first- and second-line treatment of the study groups were 49.9(95%
      CI: 40.1~59.8) months and 34.8 (95% CI: 26.3~43.3) months (P=0.189),
      respectively. Conclusion: The combination of bevacizumab and chemotherapy had a
      promising efficacy in Chinese mCRC patients. However, their OS were statistically
      insignificant between first- and second-line of bevacizumab groups.

PMID- 27698932
TI  - Detecting Circulating Tumor DNA in Hepatocellular Carcinoma Patients Using
      Droplet Digital PCR Is Feasible and Reflects Intratumoral Heterogeneity.
AB  - PURPOSE: Circulating tumor DNA (ctDNA) is increasingly recognized as liquid
      biopsy to profile tumor genome. Droplet digital PCR (ddPCR) is a highly sensitive
      and easily operable platform for mutant detection. Here, we tried to detect ctDNA
      in hepatocellular carcinoma (HCC) patients using ddPCR. METHODS: Studies
      sequencing the genome of HCCs and COSMIC (Catalogue of Somatic Mutations in
      Cancer) database were reviewed to identify hotspot mutations. Circulating cell
      free DNAs (cfDNAs) extracted from 1 ml preoperative plasma sample were analyzed
      to detect circulating mutants using ddPCR. The DNAs from matched tumor and
      adjacent liver tissues or peripheral blood mononuclear cells (PBMCs) were
      sequenced to identify the origin of circulating mutants. RESULTS: Forty-eight HCC
      patients were enrolled and four gene loci, TP53 (c.747G>T), CTNNB1 (c.121A>G,
      c.133T>C), and TERT (c.1-124C>T) were chosen as targets for ddPCR assay. Serial
      dilution demonstrated the detection limit of ddPCR to be 0.01%. Twenty-seven
      patients (56.3%, 27/48) were found to have at least one kind of circulating
      mutants, with the mutant allele frequency ranging from 0.33% to 23.7%. Six
      patients (22.2%, 6/27) also had matched mutants in tumor tissues while none of
      the mutants were detected in adjacent liver tissues or PBMCs in all patients,
      which excluded the nonneoplastic origin of these circulating mutants and
      qualified them as ctDNA. CONCLUSIONS: ctDNA could be readily detected in HCC
      patients by targeting hotspot mutations using ddPCR and might reflect
      intratumoral heterogeneity. ctDNA detecting may serve as a promising liquid
      biopsy in HCC management.

PMID- 27698934
TI  - Reversal of Vascular Calcification and Aneurysms in a Rat Model Using Dual
      Targeted Therapy with EDTA- and PGG-Loaded Nanoparticles.
AB  - Degeneration of elastic lamina and vascular calcification are common features of
      vascular pathology such as aortic aneurysms. We tested whether dual therapy with
      targeted nanoparticles (NPs) can remove mineral deposits (by delivery of a
      chelating agent, ethylene diamine tetraacetic acid (EDTA)) and restore elastic
      lamina (by delivery of a polyphenol, pentagalloyl glucose (PGG)) to reverse
      moderate aneurysm development. EDTA followed by PGG NP delivery led to reduction
      in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin
      degradation and calcification in the aorta as compared to delivery of control
      blank NPs. Such dual therapy restored vascular elastic lamina and improved
      vascular function as observed by improvement in circumferential strain.
      Therefore, dual targeted therapy may be an attractive option to remove mineral
      deposits and restore healthy arterial structures in moderately developed
      aneurysms.

PMID- 27698933
TI  - Screening of Pleural Mesotheliomas for DNA-damage Repair Players by Digital Gene
      Expression Analysis Can Enhance Clinical Management of Patients Receiving Platin
      Based Chemotherapy.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, predominantly
      asbestos-related and biologically highly aggressive tumour leading to a dismal
      prognosis. Multimodality therapy consisting of platinum-based chemotherapy is the
      treatment of choice. The reasons for the rather poor efficacy of platinum
      compounds remain largely unknown. MATERIAL AND METHODS: For this exploratory mRNA
      study, 24 FFPE tumour specimens were screened by digital gene expression
      analysis. Based on data from preliminary experiments and recent literature, a
      total of 366 mRNAs were investigated using a Custom CodeSet from NanoString. All
      statistical analyses were calculated with the R i386 statistical programming
      environment. RESULTS: CDC25A and PARP1 gene expression were correlated with lymph
      node spread, BRCA1 and TP73 expression levels with higher IMIG stage. NTHL1 and
      XRCC3 expression was associated with TNM stage. CHECK1 as well as XRCC2
      expression levels were correlated with tumour progression in the overall cohort
      of patients. CDKN2A and MLH1 gene expression influenced overall survival in this
      collective. In the adjuvant treated cohort only, CDKN2A, CHEK1 as well as ERCC1
      were significantly associated with overall survival. Furthermore, TP73 expression
      was associated with progression in this subgroup. CONCLUSION: DNA-damage response
      plays a crucial role in response to platin-based chemotherapeutic regimes. In
      particular, CHEK1, XRCC2 and TP73 are strongly associated with tumour
      progression. ERCC1, MLH1, CDKN2A and most promising CHEK1 are prognostic markers
      for OS in MPM. TP73, CDKN2A, CHEK1 and ERCC1 seem to be also predictive markers
      in adjuvant treated MPMs. After a prospective validation, these markers may
      improve clinical and pathological practice, finally leading to a patients'
      benefit by an enhanced clinical management.

PMID- 27698935
TI  - Specific Inhibition of DNMT3A/ISGF3gamma Interaction Increases the Temozolomide
      Efficiency to Reduce Tumor Growth.
AB  - DNA methylation is a fundamental feature of genomes and is a candidate for
      pharmacological manipulation that might have important therapeutic advantage.
      Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug
      intervention. By focusing on interactions existing between DNMT3A and DNMT3A
      binding protein (D3A-BP), our work identifies the DNMT3A/ISGF3gamma interaction
      such as a biomarker whose the presence level is associated with a poor survival
      prognosis and with a poor prognosis of response to the conventional
      chemotherapeutic treatment of glioblastoma multiforme (radiation plus
      temozolomide). Our data also demonstrates that the disruption of
      DNMT3A/ISGF3gamma interactions increases the efficiency of chemotherapeutic
      treatment on established tumors in mice. Thus, our data opens a promising and
      innovative alternative to the development of specific DNMT inhibitors.

PMID- 27698936
TI  - Magnetic Enrichment of Dendritic Cell Vaccine in Lymph Node with Fluorescent
      Magnetic Nanoparticles Enhanced Cancer Immunotherapy.
AB  - Dendritic cell (DC) migration to the lymph node is a key component of DC-based
      immunotherapy. However, the DC homing rate to the lymphoid tissues is poor, thus
      hindering the DC-mediated activation of antigen-specific T cells. Here, we
      developed a system using fluorescent magnetic nanoparticles (alpha-AP-fmNPs;
      loaded with antigen peptide, iron oxide nanoparticles, and indocyanine green) in
      combination with magnetic pull force (MPF) to successfully manipulate DC
      migration in vitro and in vivo. alpha-AP-fmNPs endowed DCs with MPF
      responsiveness, antigen presentation, and simultaneous optical and magnetic
      resonance imaging detectability. We showed for the first time that alpha-AP-fmNP
      loaded DCs were sensitive to MPF, and their migration efficiency could be
      dramatically improved both in vitro and in vivo through MPF treatment. Due to the
      enhanced migration of DCs, MPF treatment significantly augmented antitumor
      efficacy of the nanoparticle-loaded DCs. Therefore, we have developed a
      biocompatible approach with which to improve the homing efficiency of DCs and
      subsequent anti-tumor efficacy, and track their migration by multi-modality
      imaging, with great potential applications for DC-based cancer immunotherapy.

PMID- 27698937
TI  - Activation of GLP-1 Receptor Enhances Neuronal Base Excision Repair via PI3K-AKT
      Induced Expression of Apurinic/Apyrimidinic Endonuclease 1.
AB  - Glucagon-like peptide-1 (GLP-1) is an intestinal-secreted incretin that increases
      cellular glucose up-take to decrease blood sugar. Recent studies, however,
      suggest that the function of GLP-1 is not only to decrease blood sugar, but also
      acts as a neurotrophic factor that plays a role in neuronal survival, neurite
      outgrowth, and protects synaptic plasticity and memory formation from effects of
      beta-amyloid. Oxidative DNA damage occurs during normal neuron-activity and in
      many neurological diseases. Our study describes how GLP-1 affected the ability of
      neurons to ameliorate oxidative DNA damage. We show that activation of GLP-1
      receptor (GLP-1R) protect cortical neurons from menadione induced oxidative DNA
      damage via a signaling pathway involving enhanced DNA repair. GLP-1 stimulates
      DNA repair by activating the cyclic AMP response element binding protein (CREB)
      which, consequently, induces the expression of apurinic/apyrimidinic endonuclease
      1 (APE1), a key enzyme in the base excision DNA repair (BER) pathway. In this
      study, APE1 expression was down-regulated as a consequence phosphatidylinositol-3
      kinase (PI3K) suppression by the inhibitor LY294002, but not by the suppression
      of MEK activity. Ischemic stroke is typically caused by overwhelming oxidative
      stress in brain cells. Administration of exentin-4, an analogue of GLP-1,
      efficiently enhanced DNA repair in brain cells of ischemic stroke rats. Our study
      suggests that a new function of GLP-1 is to elevate DNA repair by inducing the
      expression of the DNA repair protein APE1.

PMID- 27698938
TI  - Optical Imaging of Mesenchymal Epithelial Transition Factor (MET) for Enhanced
      Detection and Characterization of Primary and Metastatic Hepatic Tumors.
AB  - Purpose: To assess optical imaging of Mesenchymal-Epithelial Transition factor
      (MET) for delineation and characterization of intrahepatic models of human
      hepatocellular carcinoma (HCC) and metastatic colorectal cancer (CRC), and
      thereby demonstrate its potential use in precision oncology. Materials and
      Methods: MET expression in human CRC and HCC was assessed in tissue microarrays.
      We used GE-137, a modified cyanine 5-tagged peptide for MET targeting. HepG2 and
      Huh-7 (HCC) and HT-29 (CRC) cells with MET overexpression, and LNCaP cells
      (negative control) with minimal MET expression were incubated with the probe.
      Correlation between the relative fluorescence signal intensity and cellular MET
      expression level was assessed. Flow cytometry was used to assess probe specific
      binding and dissociation constant (Kd). Orthotopic xenograft models of human HCC
      and metastatic CRC were generated in nu/nu mice by subcapsular implantation of
      cells. Epifluorescence imaging was performed to capture the changes in
      deferential probe accumulation at different time points after injection. Target
      to-liver background ratio (TBR) was calculated and the probe biodistribution
      within different organs was assessed. Histopathologic analysis of extracted
      xenografts was performed to correlate the tumors MET expression with probe uptake
      by cancer cells. Results: Approximately 91.5% of HCC and 81% of CRC microarray
      cores showed MET expression. HCC and CRC cells incubated with the probe showed
      substantial fluorescence compared to control LNCaP, with strong correlation
      between fluorescence signal and MET expression (R2 = 0.99, p < 0.001). Probe
      binding affinity to MET (Kd) was measured to be 2.9 +/- 0.36 nM. Epifluorescence
      imaging showed intense uptake in subcapsular tumors with peak TBR of 5.46 +/-
      0.46 in Huh-7, 3.55 +/- 0.38 in HepG2, and 15.93 +/- 0.61 in HT-29 orthotopic
      xenografts at 4 hours post-injection (mean +/- standard deviation). We
      demonstrated that in vivo probe uptake in xenografts is specific and can be
      blocked when co-injected with unlabeled peptide; for instance the epifluorescence
      TBR is reduced from 13.5 +/- 1.2 to 1.7 +/- 0.3 (p < 0.05) in HT-29 and from 5.3
      +/- 0.8 to 1.4 +/- 0.2 (p < 0.05) in Huh-7 xenografts after co-injection with
      unlabeled peptides. Biodistribution studies showed predominantly renal clearance
      of the probe. Conclusion: Optical imaging of MET resulted in high TBR in animal
      models of primary and metastatic hepatic tumors suggesting its utility for
      procedural guidance.

PMID- 27698939
TI  - Size Dependent Kinetics of Gold Nanorods in EPR Mediated Tumor Delivery.
AB  - Gold nanorods (AuNR) have been intensively used in nanomedicine for cancer
      diagnostics and therapy, due to their excellent plasmonic photothermal
      properties. Tuning the size and aspect ratio of AuNR tailors the localized
      surface plasmon resonance (LSPR) in the NIR spectrum at which biological tissues
      are transparent, thus enables specific and effective treatment. The AuNR
      extravasates into tumor interstitium through enhanced permeation and retention
      (EPR) effect. Efficient AuNR based cancer therapy requires efficient AuNR tumor
      delivery. However, the size of AuNR can dramatically affect its blood circulation
      and tumor accumulation. Here we proposed for the first time a systematic
      framework to investigate the size-dependent kinetics of AuNRs during EPR mediated
      tumor delivery. By using 64Cu-labeled AuNRs with positron emission tomography
      (PET) and kinetic modeling, the in vivo uptake and kinetics of 64Cu-AuNR during
      its blood circulation, tumor accumulation and elimination were studied both in
      vitro and in vivo. The results of different sized AuNRs were compared and the
      optimum size of AuNR was suggested for EPR mediated tumor delivery. Our study
      provides a better understanding of the in vivo behavior of AuNR, which can help
      future design of nanomaterials for cancer imaging and therapy.

PMID- 27698940
TI  - Blocking the 4-1BB Pathway Ameliorates Crystalline Silica-induced Lung
      Inflammation and Fibrosis in Mice.
AB  - Long term pulmonary exposure to crystalline silica leads to silicosis that
      manifests progressive interstitial fibrosis, eventually leading to respiratory
      failure and death. Despite efforts to eliminate silicosis, clinical cases
      continue to occur in both developing and developed countries. The exact
      mechanisms of crystalline silica-induced pulmonary fibrosis remain elusive.
      Herein, we find that 4-1BB is induced in response to crystalline silica injury in
      lungs and that it is highly expressed during development of experimental
      silicosis. Therefore, we explore the role of 4-1BB pathway during crystalline
      silica-induced lung injury and find that a specific inhibitor blocking the
      pathway could effectively alleviate crystalline silica-induced lung inflammation
      and subsequent pulmonary fibrosis in vivo. Compared to controls, the treated mice
      exhibited reduced Th1 and Th17 responses. The concentrations of pro-inflammatory
      cytokines in bronchoalveolar lavage fluid (BALF), including tumor necrosis factor
      (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-17A following
      crystalline silica challenge were also reduced in inhibitor-treated mice.
      Although there was no significant alteration in Th2 cytokines of IL-4 and IL-13,
      another type of pro-fibrogenic cell, regulatory T cell (Treg) was significantly
      affected. In addition, one of the major participants in fibrogenesis, fibrocyte
      recruited less due to the blockade. Furthermore, we demonstrated the decreased
      fibrocyte recruitment was associated with chemokine reductions in lung. Our study
      discovers the 4-1BB pathway signaling enhances inflammatory response and promotes
      pulmonary fibrosis induced by crystalline silica. The findings here provide novel
      insights into the molecular events that control crystalline silica-induced lung
      inflammation and fibrosis through regulating Th responses and the recruitment of
      fibrocytes in crystalline silica-exposed lung.

PMID- 27698941
TI  - Crucial Role of miR-433 in Regulating Cardiac Fibrosis.
AB  - Dysregulation of microRNAs has been implicated in many cardiovascular diseases
      including fibrosis. Here we report that miR-433 was consistently elevated in
      three models of heart disease with prominent cardiac fibrosis, and was enriched
      in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in
      neonatal rat cardiac fibroblasts increased proliferation and their
      differentiation into myofibroblasts as determined by EdU incorporation, alpha-SMA
      staining, and expression levels of fibrosis-associated genes. Conversely,
      inhibition of miR-433 exhibited opposite results. AZIN1 and JNK1 were identified
      as two target genes of miR-433. Decreased level of AZIN1 activated TGF-beta1
      while down-regulation of JNK1 resulted in activation of ERK and p38 kinase
      leading to Smad3 activation and ultimately cardiac fibrosis. Importantly,
      systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated
      cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular
      dysfunction following myocardial infarction. Thus, our work suggests that miR-433
      is a potential target for amelioration of cardiac fibrosis.

PMID- 27698942
TI  - Optimization of Early Response Monitoring and Prediction of Cancer
      Antiangiogenesis Therapy via Noninvasive PET Molecular Imaging Strategies of
      Multifactorial Bioparameters.
AB  - Objective: Antiangiogenesis therapy (AAT) has provided substantial benefits
      regarding improved outcomes and survival for suitable patients in clinical
      settings. Therefore, the early definition of therapeutic effects is urgently
      needed to guide cancer AAT. We aimed to optimize the early response monitoring
      and prediction of AAT efficacy, as indicated by the multi-targeted anti
      angiogenic drug sunitinib in U87MG tumors, using noninvasive positron emission
      computed tomography (PET) molecular imaging strategies of multifactorial
      bioparameters. Methods: U87MG tumor mice were treated via intragastric injections
      of sunitinib (80 mg/kg) or vehicle for 7 consecutive days. Longitudinal
      MicroPET/CT scans with 18F-FDG, 18F-FMISO, 18F-ML-10 and 18F-Alfatide II were
      acquired to quantitatively measure metabolism, hypoxia, apoptosis and
      angiogenesis on days 0, 1, 3, 7 and 13 following therapy initiation. Tumor
      tissues from a dedicated group of mice were collected for immunohistochemical
      (IHC) analysis of key biomarkers (Glut-1, CA-IX, TUNEL, alphanubeta3 and CD31) at
      the time points of PET imaging. The tumor sizes and mouse weights were measured
      throughout the study. The tumor uptake (ID%/gmax), the ratios of the tumor/muscle
      (T/M) for each probe, and the tumor growth ratios (TGR) were calculated and used
      for statistical analyses of the differences and correlations. Results: Sunitinib
      successfully inhibited U87MG tumor growth with significant differences in the
      tumor size from day 9 after sunitinib treatment compared with the control group
      (P < 0.01). The uptakes of 18F-FMISO (reduced hypoxia), 18F-ML-10 (increased
      apoptosis) and 18F-Alfatide II (decreased angiogenesis) in the tumor lesions
      significantly changed during the early stage (days 1 to 3) of sunitinib
      treatment; however, the uptake of 18F-FDG (increased glucose metabolism) was
      significantly different during the late stage. The PET imaging data of each probe
      were all confirmed via ex vivo IHC of the relevant biomarkers. Notably, the PET
      imaging of 18F-Alfatide II and 18F-FMISO was significantly correlated (all P <
      0.05) with TGR, whereas the imaging of 18F-FDG and 18F-ML-10 was not
      significantly correlated with TGR. Conclusion: Based on the tumor uptake of the
      PET probes and their correlations with MVD and TGR, 18F-Alfatide II PET may not
      only monitor the early response but also precisely predict the therapeutic
      efficacy of the multi-targeted, anti-angiogenic drug sunitinib in U87MG tumors.
      In conclusion, it is feasible to optimize the early response monitoring and
      efficacy prediction of cancer AAT using noninvasive PET molecular imaging
      strategies of multifactorial bioparameters, such as angiogenesis imaging with 18F
      Alfatide II, which represents an RGD-based probe.

PMID- 27698943
TI  - Intracellular Trafficking Network of Protein Nanocapsules: Endocytosis,
      Exocytosis and Autophagy.
AB  - The inner membrane vesicle system is a complex transport system that includes
      endocytosis, exocytosis and autophagy. However, the details of the intracellular
      trafficking pathway of nanoparticles in cells have been poorly investigated.
      Here, we investigate in detail the intracellular trafficking pathway of protein
      nanocapsules using more than 30 Rab proteins as markers of multiple trafficking
      vesicles in endocytosis, exocytosis and autophagy. We observed that FITC-labeled
      protein nanoparticles were internalized by the cells mainly through Arf6
      dependent endocytosis and Rab34-mediated micropinocytosis. In addition to this
      classic pathway: early endosome (EEs)/late endosome (LEs) to lysosome, we
      identified two novel transport pathways: micropinocytosis (Rab34 positive)-LEs
      (Rab7 positive)-lysosome pathway and EEs-liposome (Rab18 positive)-lysosome
      pathway. Moreover, the cells use slow endocytosis recycling pathway (Rab11 and
      Rab35 positive vesicles) and GLUT4 exocytosis vesicles (Rab8 and Rab10 positive)
      transport the protein nanocapsules out of the cells. In addition, protein
      nanoparticles are observed in autophagosomes, which receive protein nanocapsules
      through multiple endocytosis vesicles. Using autophagy inhibitor to block these
      transport pathways could prevent the degradation of nanoparticles through
      lysosomes. Using Rab proteins as vesicle markers to investigation the detail
      intracellular trafficking of the protein nanocapsules, will provide new targets
      to interfere the cellular behaver of the nanoparticles, and improve the
      therapeutic effect of nanomedicine.

PMID- 27698944
TI  - Gelatin-based Hydrogel Degradation and Tissue Interaction in vivo: Insights from
      Multimodal Preclinical Imaging in Immunocompetent Nude Mice.
AB  - Hydrogels based on gelatin have evolved as promising multifunctional
      biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI)
      and the molar ratio of gelatin and LDI in the starting material mixture
      determines elastic properties of the resulting hydrogel. In order to investigate
      the clinical potential of these biopolymers, hydrogels with different ratios of
      gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess
      of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral
      implantation). Degradation and biomaterial-tissue-interaction were investigated
      in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology,
      serum analysis). Multimodal imaging revealed that the number of covalent net
      points correlates well with degradation time, which allows for targeted
      modification of hydrogels based on properties of the tissue to be replaced.
      Importantly, the degradation time was also dependent on the number of implants
      per animal. Despite local mechanisms of tissue remodeling no adverse tissue
      responses could be observed neither locally nor systemically. Finally, this
      preclinical investigation in immunocompetent mice clearly demonstrated a complete
      restoration of the original healthy tissue.

PMID- 27698945
TI  - Proto-Oncogenic Src Phosphorylates EB1 to Regulate the Microtubule-Focal Adhesion
      Crosstalk and Stimulate Cell Migration.
AB  - Cell migration, a complex process critical for tumor progression and metastasis,
      requires a dynamic crosstalk between microtubules (MTs) and focal adhesions
      (FAs). However, the molecular mechanisms underlying this event remain elusive.
      Herein we identify the proto-oncogenic protein Src as an important player in the
      regulation of the MT-FA crosstalk. Src interacts with and phosphorylates end
      binding protein 1 (EB1), a member of MT plus end-tracking proteins (+TIPs), both
      in cells and in vitro. Systematic mutagenesis reveals that tyrosine-247 (Y247) is
      the primary residue of EB1 phosphorylated by Src. Interestingly, both
      constitutively activated Src and Y247-phosphorylated EB1 localize to the
      centrosome and FAs. Src-mediated EB1 phosphorylation diminishes its interactions
      with other +TIPs, including adenomatous polyposis coli (APC) and mitotic
      centromere associated kinesin (MCAK). In addition, EB1 phosphorylation at Y247
      enhances the rate of MT catastrophe and significantly stimulates cell migration.
      These findings thus demonstrate that the Src-EB1 axis plays a crucial role in
      regulating the crosstalk between MTs and FAs to promote cell migration.

PMID- 27698946
TI  - A New Concept of Enhancing Immuno-Chemotherapeutic Effects Against B16F10 Tumor
      via Systemic Administration by Taking Advantages of the Limitation of EPR Effect.
AB  - The enhanced permeability and retention (EPR) effect has been comfortably
      accepted, and extensively assumed as a keystone in the research on tumor-targeted
      drug delivery system. Due to the unsatisfied tumor-targeting efficiency of EPR
      effect being one conspicuous drawback, nanocarriers that merely relying on EPR
      effect are difficult to access the tumor tissue and consequently trigger
      efficient tumor therapy in clinic. In the present contribution, we break up the
      shackles of EPR effect on nanocarriers thanks to their universal distribution
      characteristic. We successfully design a paclitaxel (PTX) and alpha
      galactosylceramide (alphaGC) co-loaded TH peptide (AGYLLGHINLHHLAHL(Aib)HHIL-Cys)
      -modified liposome (PTX/alphaGC-TH-Lip) and introduce a new concept of immuno
      chemotherapy combination via accumulation of these liposomes at both spleen and
      tumor sites naturally and simultaneously. The PTX-initiated cytotoxicity attacks
      tumor cells at tumor sites, meanwhile, the alphaGC-triggered antitumor immune
      response emerges at spleen tissue. Different to the case that liposomes are
      loaded with sole drug, in this concept two therapeutic processes effectively
      reinforce each other, thereby elevating the tumor therapy efficiency
      significantly. The data demonstrates that the PTX/alphaGC-TH-Lip not only possess
      therapeutic effect against highly malignant B16F10 melanoma tumor, but also
      adjust the in vivo immune status and induce a more remarkable systemic antitumor
      immunity that could further suppress the growth of tumor at distant site. This
      work exhibits the capability of the PTX/alphaGC-TH-Lip in improving immune
      chemotherapy against tumor after systemic administration.

PMID- 27698947
TI  - Synthesis of thiazolidine-2,4-dione derivatives: anticancer, antimicrobial and
      DNA cleavage studies.
AB  - In the search of efficient anticancer agents, here, new 5-(4
      alkylbenzyledene)thiazolidine-2,4-dione derivatives (5a-g) have been successfully
      synthesized and characterized and are evaluated for anticancer and antimicrobial
      activities using DNA cleavage studies. In vitro studies on anticancer activity of
      compound 5d (NSC: 768619/1) was done against the full panel of 60 human tumor
      cell lines. The five-level dose activity results revealed that, the compound 5d
      was active against all the cell lines, it has shown potential activity against
      leukemia SR (GI50: 2.04 MUM), non-small cell lung cancer NCI-H522 (GI50: 1.36
      MUM), colon cancer COLO 205 (GI50: 1.64 MUM), CNS cancer SF-539 (GI50: 1.87 MUM),
      melanoma SK-MEL-2 (GI50: 1.64 MUM), ovarian cancer OVCAR-3 (GI50: 1.87 MUM),
      renal cancer RXF 393 (GI50: 1.15 MUM), prostate cancer PC-3 (GI50: 1.90 MUM), and
      breast cancer MDA-MB-468(GI50: 1.11 MUM). DNA cleavage studies revealed that at
      50 MUg/mL concentration, partial DNA digestion was observed and when the
      concentration is increasing to threefold (150 MUg/mL), complete linear DNA
      digestion and partial supercoiled DNA digestion was observed. Further
      antimicrobial studies indicate that all the synthesized compounds except compound
      5a possess prominent activity against all the screened microbial species. This
      study throws a ray of light in the field of anticancer drugs.

PMID- 27698948
TI  - Structural insight into binding mode of inhibitor with SAHH of Plasmodium and
      human: interaction of curcumin with anti-malarial drug targets.
AB  - S-adenosyl-L-homocysteine hydrolase of Plasmodium falciparum (PfSAHH) is a
      potential drug target against malaria, and selective inhibition of PfSAHH is the
      excellent strategy to prevent the growth of parasite inside the host. Therefore,
      a comparative analysis of human S-adenosyl-L-homocysteine hydrolase (HsSAHH) and
      PfSAHH has been performed to explore the structural differences. Structural
      superimposition of PfSAHH and HsSAHH has generated the RMSD of 0.749 A over 394
      alpha carbon pairs. Residues of PfSAHH from position Tyr152 to Lys193 aligned
      with insertion/deletion region in HsSAHH, and these extra residues results in an
      extent of variation in cavity region of PfSAHH. Nicotinamide adenine dinucleotide
      (NAD) was observed to form hydrogen bonding with Thr201, Thr202, Thr203, Asn235,
      Val268, Glu287, Asn322, Ile343, Asn391, Lys473, and Tyr477 and also forms
      hydrophobic interactions with Val268, Ile288, and Thr320 of PfSAHH. In comparison
      to HsSAHH, Asn322, Lys473, and Tyr477 residues of PfSAHH are unique in
      interaction with NAD. 2-Fluoroaristeromycin and other analogues of aristeromycin
      have shown the good binding affinity for both enzymes. Structural differences
      between PfSAHH and HsSAHH might be employed to design the potential inhibitor of
      PfSAHH. To find the target enzyme responsible for an anti-malarial effect,
      molecular docking and interaction analysis of curcumin were performed with 34
      drug targets of P. falciparum. Curcumin shows high affinity for binding with
      HGPRT of PfHGPRT, and an anti-malarial effect of curcumin might be due to binding
      with PfHGPRT.

PMID- 27698949
TI  - Influence of organic solvents on the structural and thermal characteristics of
      silk protein from the web of Orthaga exvinacea Hampson (Lepidoptera: Pyralidae).
AB  - The silk protein from the web of Orthaga exvinacea was isolated, purified, and
      casted into films. This film was treated separately with methanol, acetone, ethyl
      acetate, and isopropyl alcohol in 50 % concentration for about 30 min. The
      treated films were thus dried in a desiccator and subjected to FTIR and TG-DTA
      analysis. The structural studies revealed that the organic solvents induce
      conformatory changes in the protein film, especially the most sensitive amide I
      (1650 cm-1) band. This band had shifted to lower wavenumber (1633-1636 cm-1).
      Furthermore, the conformatory characteristics associated with amide I band also
      changed from random coil to beta-sheet. Generally, beta-sheet contributes
      strength to the protein film. Among the treated films, film treated with acetone
      showed much thermal stability. Moreover, the film treated with methanol had shown
      two different temperatures of maximum degradation. It is concluded that in
      addition to beta-sheet content, various other factors such as various processing
      conditions and structural organization of protein may influence the stability of
      the films.

PMID- 27698951
TI  - JOCB Bulletin.

PMID- 27698950
TI  - The removal of mercury (II) from water by Ag supported on nanomesoporous silica.
AB  - In this study, the synthesis of SBA-15/Ag nanocomposite materials with different
      amounts of silver (2.5, 5, and 10 %) has been investigated under acidic
      conditions by using P123 as a template via the direct method. The nanocomposites
      of SBA-15 were synthesized by the same method and by the addition of silver salt.
      Finally, the nanocomposite materials were examined for the removal of mercury
      ions from wastewater as an adsorbent by the reverse titration method.
      Characterization was carried out through x-ray diffraction analysis (XRD),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), and
      N2 adsorption-desorption (Brunauer-Emmett-Teller). XRD spectra confirmed the
      presence of silver nanoparticles within the amorphous silica matrix of SBA-15.
      The Barrett-Joyner-Halenda analysis showed that SBA-15 and SBA-15/Ag have a
      narrow pore size distribution. SEM images demonstrated that the morphology of the
      matrix of SBA-15 is in spherical state. Furthermore, wavelength dispersive x-ray
      spectroscopy identified the presence and distribution of silver nanoparticles
      inside the pore channels and outside of them. Typical TEM images of SBA-15 and
      SBA-15/Ag (5 wt.%) indicated a regular hexagonal pore structure with long-range
      order and long channels. In SBA-15/Ag (5 wt.%) sample, the nanoparticles of
      silver was found into the pores and outside of them. The removal of mercury ions
      from wastewater using mesoporous silica nanocomposite containing silver
      nanoparticles was studied by the reverse titration analysis. The best capacity of
      adsorption of mercury ions from wastewater was obtained for SBA-15/Ag (5 wt.%)
      sample, which was equal to 42.26 mg/g in 20 min at pH of 7. The Freundlich model
      was used to explain the adsorption characteristics for the heterogeneous surface,
      and [Formula: see text] (adsorption capacity) and n (adsorption intensity) were
      determined for Hg (II) ion adsorption on SBA-15/Ag nanocomposite materials with
      different amounts of silver (2.5, 5, and 10 %). The value of R2 was about 0.99,
      0.99, 0.98, and 0.98 and Kf was about 42, 48, 58, and 58 mg/g for SBA-15/Ag, SBA
      15/Ag (2.5 %), SBA-15/Ag (5 %), and SBA-15/Ag (10 %), respectively. Furthermore,
      the values of n >1 show a favorable adsorption process for Hg (II) ion adsorption
      on SBA-15/Ag nanocomposite materials. Moreover, the Langmuir isotherm model
      evaluation showed that the correlation coefficients for all concentrations were
      R2 >0.99, indicating that Hg (II) ions were adsorbed on the surface of SBA-15/Ag
      via chemical and physical interaction. Additionally, the analytic hierarchy
      process (AHP) and Technique of Order Preference Similarity to the Ideal Solution
      (TOPSIS) methods that depend on the criteria of the surface area, amount of
      adsorbent, pore volume, and cost of synthesis were used. The evaluation of
      results showed that the best sample was SBA-15/Ag (5 wt.%). Furthermore, the
      research work highlighted the antibacterial nanocomposite with suitable
      adsorption of Hg (II) ions from water solutions and supported its potential for
      environmental applications. This nanocomposite can be used in the absorption
      domain of Hg (II) ions from water solutions.

PMID- 27698952
TI  - Epigallocatechin-3-gallate Attenuates Renal Damage by Suppressing Oxidative
      Stress in Diabetic db/db Mice.
AB  - Epigallocatechin-3-gallate (EGCG), extracted from green tea, has been shown to
      have antioxidative activity. In the present study, we evaluated the effect of
      EGCG on the kidney function in db/db mice and also tried to investigate the
      underlying mechanism of the renoprotective effects of EGCG in both animals and
      cells. EGCG treatment could decrease the level of urinary protein, 8-iso-PGF2a,
      and Ang II. Moreover, EGCG could also change the level of several parameters
      associated with oxidative stress. In addition, the protein expression levels of
      AT-1R, p22-phox, p47-phox, p-ERK1/2, p-p38 MAPK, TGF-beta1, and alpha-SMA in
      diabetic db/db mice were upregulated, and all of these symptoms were
      downregulated with the treatment of EGCG at 50 and 100 mg/kg/d. Furthermore, the
      pathological changes were ameliorated in db/db mice after EGCG treatment. HK-2
      cell-based experiments indicated that EGCG could inhibit the expression of MAPK
      pathways, which is the downstream effector of Ang II mediated oxidative stress.
      All these results indicated that EGCG treatment could ameliorate changes of renal
      pathology and delay the progression of DKD by suppressing hyperglycemia-induced
      oxidative stress in diabetic db/db mice.

PMID- 27698953
TI  - Training Enhances Immune Cells Mitochondrial Biosynthesis, Fission, Fusion, and
      Their Antioxidant Capabilities Synergistically with Dietary Docosahexaenoic
      Supplementation.
AB  - Exercise training induces adaptations in mitochondrial metabolism, dynamics, and
      oxidative protection. Omega-3 fatty acids change membrane lipid composition and
      modulate mitochondrial function. The aim was to investigate the effect of 8-week
      training and docosahexaenoic acid (DHA) supplementation (1.14 g/day) on the
      mitochondria dynamics and antioxidant status in peripheral blood mononuclear
      cells (PBMCs) from sportsmen. Subjects were assigned to an intervention (N = 9)
      or placebo groups (N = 7) in a randomized double-blind trial. Nutritional
      intervention significantly increased the DHA content in erythrocyte membranes
      from the experimental group. No significant differences were reported in terms of
      circulating PBMCs, Mn-superoxide dismutase protein levels, and their capability
      to produce reactive oxygen species. The proteins related to mitochondrial
      dynamics were, in general, increased after an 8-week training and this increase
      was enhanced by DHA supplementation. The content in mitofusins Mtf-1 and Mtf-2,
      optic atrophy protein-1 (Opa-1), and mitochondrial transcription factor A (Tfam)
      were significantly higher in the DHA-supplemented group after intervention.
      Cytochrome c oxidase (COX-IV) activity and uncoupling proteins UCP-2 and UCP-3
      protein levels were increased after training, with higher UCP-3 levels in the
      supplemented group. In conclusion, training induced mitochondrial adaptations
      which may contribute to improved mitochondrial function. This mitochondrial
      response was modulated by DHA supplementation.

PMID- 27698954
TI  - Korean pine nut oil replacement decreases intestinal lipid uptake while improves
      hepatic lipid metabolism in mice.
AB  - BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce
      weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD).
      The aim of this study was to examine the effects of PNO on both intestinal and
      hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week
      old C57BL/6 mice were fed control diets containing 10% energy fat from either
      Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30%
      energy fat from SBO or PNO for 12 weeks. Expression of genes related to
      intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp),
      intestinal chylomicron synthesis (Mtp, ApoB48, ApoA4), hepatic lipid uptake and
      channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TAG) lipolysis
      and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low-density
      lipoprotein (VLDL) assembly (ApoB100) were determined by real-time PCR. RESULTS:
      In intestine, significantly lower Cd36 mRNA expression (P < 0.05) and a tendency
      of lower ApoA4 mRNA levels (P = 0.07) was observed in PNO-fed mice, indicating
      that PNO consumption may decrease intestinal FA uptake and chylomicron assembly.
      PNO consumption tended to result in higher hepatic mRNA levels of Atgl (P = 0.08)
      and Cpt1a (P = 0.05). Significantly higher hepatic mRNA levels of Acadl and
      ApoB100 were detected in mice fed PNO diet (P < 0.05). These results suggest that
      PNO could increase hepatic TAG metabolism; mitochondrial fatty acid oxidation and
      VLDL assembly. CONCLUSIONS: PNO replacement in the diet might function in
      prevention of excessive lipid uptake by intestine and improve hepatic lipid
      metabolism in both control diet and HFD fed mice.

PMID- 27698955
TI  - Korean Curcuma longa L. induces lipolysis and regulates leptin in adipocyte cells
      and rats.
AB  - BACKGROUND/OBJECTIVES: Turmeric (Curcuma longa L.) has been reported to have many
      biological functions including anti-obesity. Leptin, peptide hormone produced by
      adipocytes and its concentration is increased in proportion to the amount of the
      adipocytes. In the present study, we examined the effects of Korean turmeric on
      the regulation of adiposity and leptin levels in 3T3-L1 adipocytes and rats fed a
      high-fat and high-cholesterol diet. MATERIALS/METHODS: Leptin secretion, free
      fatty acid and glycerol contents in 3T3-L1 adipocytes were measured after
      incubation of cells with turmeric for 24 hours. Rats were divided into four
      experimental groups: a normal diet group (N), a high-fat and high-cholesterol
      diet group (HF), a high-fat and high-cholesterol diet group supplemented with
      2.5% turmeric extracts (TPA group) and a high-fat and high-cholesterol diet group
      supplemented with 5% turmeric extracts (TPB group). Serum samples were used for
      the measurement of leptin concentration. RESULTS: Contents of free fatty acid and
      glycerol showed concentration dependent increase in response to turmeric
      extracts. Effects of turmeric extracts on reduction of lipid accumulation in 3T3
      L1 cells were examined by Oil Red O staining. Treatment with turmeric extracts
      resulted in increased expression levels of adipose triglyceride lipase and
      hormone-sensitive lipase mRNA. The concentration of leptin from 3T3-L1 adipocytes
      was significantly decreased by turmeric. Proportional abdominal and epididymal
      fats weights of the turmeric 5% supplemented group, TPB has significantly
      decreased compared to the HF group. The serum levels of leptin in the TPA and TPB
      groups were significantly lower than those of the HF group. CONCLUSIONS: Based on
      these results, we suggested that Korean turmeric may contribute to the decreasing
      of body fat and regulating leptin secretion.

PMID- 27698957
TI  - Corn silk extract improves cholesterol metabolism in C57BL/6J mouse fed high-fat
      diets.
AB  - BACKGROUND/OBJECTIVES: Corn silk (CS) extract contains large amounts of maysin,
      which is a major flavonoid in CS. However, studies regarding the effect of CS
      extract on cholesterol metabolism is limited. Therefore, the purpose of this
      study was to determine the effect of CS extract on cholesterol metabolism in
      C57BL/6J mouse fed high-fat diets. MATERIALS/METHODS: Normal-fat group fed 7% fat
      diet, high-fat (HF) group fed 25% fat diet, and high-fat with corn silk (HFCS)
      group were orally administered CS extract (100 mg/kg body weight) daily. Serum
      and hepatic levels of total lipids, triglycerides, and total cholesterol as well
      as serum free fatty acid, glucose, and insulin levels were determined. The mRNA
      expression levels of acyl-CoA: cholesterol acyltransferase (ACAT), cholesterol 7
      alpha hydroxylase (CYP7A1), farnesoid X receptor (FXR), lecithin cholesterol
      acyltransferase (LCAT), low-density lipoprotein receptor, 3-hyroxy-3
      methylglutaryl-coenzyme A reductase (HMG-CoA reductase), adiponectin, leptin, and
      tumor necrosis factor alpha were determined. RESULTS: Oral administration of CS
      extract with HF improved serum glucose and insulin levels as well as attenuated
      HF-induced fatty liver. CS extracts significantly elevated mRNA expression levels
      of adipocytokines and reduced mRNA expression levels of HMG-CoA reductase, ACAT,
      and FXR. The mRNA expression levels of CYP7A1 and LCAT between the HF group and
      HFCS group were not statistically different. CONCLUSIONS: CS extract
      supplementation with a high-fat diet improves levels of adipocytokine secretion
      and glucose homeostasis. CS extract is also effective in decreasing the
      regulatory pool of hepatic cholesterol, in line with decreased blood and hepatic
      levels of cholesterol though modulation of mRNA expression levels of HMG-CoA
      reductase, ACAT, and FXR.

PMID- 27698956
TI  - Blueberry, blackberry, and blackcurrant differentially affect plasma lipids and
      pro-inflammatory markers in diet-induced obesity mice.
AB  - BACKGROUND/OBJECTIVES: Evidence indicates that berry anthocyanins are anti
      atherogenic, antioxidant, and anti-inflammatory. However, berries differ vastly
      in their anthocyanin composition and thus potentially in their biological and
      metabolic effects. The present study compared hypolipidemic, antioxidant, and
      anti-inflammatory properties of blueberry (BB), blackberry (BK), and blackcurrant
      (BC) in a diet-induced obesity (DIO) mouse model. MATERIALS/METHODS: Male
      C57BL/6J mice were fed a high fat (HF; 35% fat, w/w) control diet or a HF diet
      supplemented with freeze-dried 5% BB, 6.3% BK or 5.7% BC for 12 weeks (10
      mice/group) to achieve the same total anthocyanin content in each diet. Plasma
      lipids, antioxidant status and pro-inflammatory cytokines were measured. The
      expression of genes involved in antioxidant defense, inflammation, and lipid
      metabolism was determined in the liver, epididymal adipose tissue, proximal
      intestine, and skeletal muscle. Histological analysis was performed to identify
      crown-like structure (CLS) in epididymal fat pads to determine macrophage
      infiltration. RESULTS: No differences were noted between the control and any
      berry-fed groups in plasma levels of liver enzymes, insulin, glucose, ferric
      reducing antioxidant power, superoxide dismutase, and tumor necrosis factor
      alpha. However, BK significantly lowered plasma triglyceride compared with the HF
      control and other berries, whereas BC significantly reduced F4/80 mRNA and the
      number of CLS in the epididymal fat pad, indicative of less macrophage
      infiltration. CONCLUSIONS: The present study provides evidence that BB, BK and BC
      with varying anthocyanin composition differentially affect plasma lipids and
      adipose macrophage infiltration in DIO mice, but with no differences in their
      antioxidant capacity and anti-inflammatory potential.

PMID- 27698958
TI  - Gynura procumbens extract improves insulin sensitivity and suppresses hepatic
      gluconeogenesis in C57BL/KsJ-db/db mice.
AB  - BACKGROUND/OBJECTIVES: This study was designed to investigate whether Gynura
      procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic
      glucose production in an animal model of type 2 diabetes. MATERIALS/METHODS:
      C57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE,
      and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks. RESULTS: Mice
      supplemented with GPE showed significantly lower blood levels of glucose and
      glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance
      test also showed the positive effect of GPE on increasing insulin sensitivity.
      The homeostatic index of insulin resistance was significantly lower in mice
      supplemented with GPE than in the diabetic control mice. In the skeletal muscle,
      the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of
      160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with
      GPE when compared to that of the diabetic control mice. GPE also decreased the
      expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the
      liver. CONCLUSIONS: These findings demonstrate that GPE might improve insulin
      sensitivity and inhibit gluconeogenesis in the liver.

PMID- 27698959
TI  - Intake of antioxidants and B vitamins is inversely associated with ischemic
      stroke and cerebral atherosclerosis.
AB  - BACKGROUND/OBJECTIVES: This study was conducted to examine relationships between
      dietary habits and intakes of antioxidants and B vitamins and the risk of
      ischemic stroke, and to compare dietary factors according to the presence of
      cerebral artery atherosclerosis and stroke subtypes. SUBJECTS/METHODS: A total of
      147 patients and 144 control subjects were recruited consecutively in the
      metropolitan area of Seoul, Korea. Sixty participants each in the case and
      control groups were included in analyses after 1:1 frequency matching. In
      addition, 117 acute ischemic stroke patients were classified into subtypes
      according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) guidelines.
      Dietary intake was measured using a semi-quantitative food frequency
      questionnaire composed of 111 food items and plasma lipid and homocysteine levels
      were analyzed. RESULTS: When compared with control subjects, stroke patients had
      unfavorable dietary behaviors and lower intakes of fruits (73.1 +/- 83.2 g vs.
      230.9 +/- 202.1 g, P < 0.001), vegetables (221.1 +/- 209.0 g vs. 561.7 +/- 306.6
      g, P < 0.001), and antioxidants, including vitamins C, E, B6, beta-carotene, and
      folate. The intakes of fruits, vegetables, vitamin C, and folate were inversely
      associated with the risk of ischemic stroke after adjusting for confounding
      factors. Intakes of vegetables, vitamins C, B6, B12, and folate per 1,000 kcal
      were lower in ischemic stroke with cerebral atherosclerosis than in those
      without. Overall vitamin B12 intake per 1,000 kcal differed according to the
      TOAST classification (P = 0.004), but no differences among groups existed based
      on the post-hoc test. CONCLUSIONS: When compared with control subjects, ischemic
      stroke patients, particularly those with cerebral atherosclerosis, had
      unfavorable dietary intake, which may have contributed to the development of
      ischemic stroke. These results indicate that proper dietary recommendations are
      important for the prevention of ischemic stroke.

PMID- 27698960
TI  - Effect of plate size on meal energy intake in normal weight women.
AB  - BACKGROUND/OBJECTIVES: Use of smaller plates to control food intake is a commonly
      recommended strategy for restricting energy intake, despite conflicting results.
      Therefore, the aim of this study was to examine whether or not three different
      sizes of plates influence energy intake during a multi-itemed buffet meal in
      normal weight women. SUBJECTS/METHODS: This was a cross-over study conducted on
      37 female participants aged 19-25 years with normal BMI levels. Participants were
      recruited from Hacettepe University and the surrounding community. On
      experimental days, participants ate a standard breakfast and were then randomly
      assigned to eat lunch using a small (19 cm), medium (23 cm), or large (28 cm)
      diameter plate. Visual analogue scale (VAS) scores on sensory and satiety
      outcomes were measured for all meals. Energy and macronutrient intakes during
      lunch were recorded. RESULTS: There was no evidence that use of a smaller plate
      size reduced energy or specific macronutrient intake during the free choice lunch
      meal. Multiple visits to the serving table were not associated with energy or
      macronutrient intake. Plate size did not affect VAS scores during the test days.
      CONCLUSIONS: Plate size did not influence energy intake, meal composition, or
      palatability in normal weight women during a multi-itemed open buffet lunch.
      Studies in natural settings at the population level are needed to clarify current
      outcomes.

PMID- 27698961
TI  - Food deserts in Korea? A GIS analysis of food consumption patterns at sub
      district level in Seoul using the KNHANES 2008-2012 data.
AB  - BACKGROUND/OBJECTIVES: The concept of "food deserts" has been widely used in
      Western countries as a framework to identify areas with constrained access to
      fresh and nutritious foods, providing guidelines for targeted nutrition and
      public health programs. Unlike the vast amount of literature on food deserts in a
      Western context, only a few studies have addressed the concept in an East Asian
      context, and none of them have investigated spatial patterns of unhealthy food
      consumption from a South Korean perspective. SUBJECTS/METHODS: We first evaluated
      the applicability of food deserts in a Korean setting and identified four Korean
      specific unhealthy food consumption indicators, including insufficient food
      consumption due to financial difficulty, limited consumption of fruits and
      vegetables, excessive consumption of junk food, and excessive consumption of
      instant noodles. The KNHANES 2008-2012 data in Seoul were analyzed with
      stratified sampling weights to understand the trends and basic characteristics of
      these eating patterns in each category. GIS analyses were then conducted for the
      data spatially aggregated at the sub-district level in order to create maps
      identifying areas of concern regarding each of these indicators and their
      combinations. RESULTS: Despite significant reduction in the rate of food
      insufficiency due to financial difficulty, the rates of excessive consumption of
      unhealthy foods (junk food and instant noodles) as well as limited consumption of
      fruits and vegetables have increased or remained high. These patterns tend to be
      found among relatively younger and more educated groups, regardless of income
      status. CONCLUSIONS: A GIS-based analysis demonstrated several hotspots as
      potential "food deserts" tailored to the Korean context based on the observed
      spatial patterns of undesirable food consumption. These findings could be used as
      a guide to prioritize areas for targeted intervention programs to facilitate
      healthy food consumption behaviors and thus improve nutrition and food-related
      health outcomes.

PMID- 27698962
TI  - Dietary sugar intake and dietary behaviors in Korea: a pooled study of 2,599
      children and adolescents aged 9-14 years.
AB  - BACKGROUND/OBJECTIVES: Dietary sugar intake, particularly added sugar and sugar
      sweetened beverages, has received worldwide attention recently. Investigation of
      dietary behaviors may facilitate understanding of dietary sugar intakes of
      children and adolescents. However, the relationship between dietary sugar intake
      and dietary behaviors in the Korean population has not been investigated. Thus,
      this study aimed to estimate dietary sugar intake and food sources according to
      sex as well as examine the relationship of dietary sugar intake with frequent
      snacking and dietary patterns among Korean children and adolescents.
      SUBJECTS/METHODS: We pooled data from five studies involving Korean children and
      adolescents conducted from 2002 to 2011. A total of 2,599 subjects aged 9-14
      years were included in this study. Each subject completed more than 3 days of
      dietary records. RESULTS: Mean daily total sugar intake was 46.6 g for boys and
      54.3 g for girls. Compared with boys, girls showed higher sugar intakes from
      fruits (7.5 g for boys and 8.8 g for girls; P = 0.0081) and processed foods (27.9
      g for boys and 34.9 g for girls; P < 0.0001). On average, 95.4% of boys and 98.8%
      of girls consumed snacks during the study period, and total sugar intake showed a
      significantly increasing trend with increasing energy intake from snacks (P <
      0.0001 for both sexes). Two dietary patterns were identified by cluster analysis:
      Traditional and Westernized patterns. Total sugar intake was higher in the
      Westernized pattern (56.2 g for boys and 57.2 g for girls) than in the
      Traditional pattern (46.5 g for boys and 46.3 g for girls). CONCLUSIONS: These
      results suggest that multilateral and practical development of a nutrition
      education and intervention program that considers dietary behaviors as well as
      absolute sugar intake is required to prevent excessive sugar intake in Korean
      children and adolescents.

PMID- 27698963
TI  - Perception of sugar reduction, nutrition education, and frequency of snacking in
      children by the self-perceived sweet dietary habits of mothers in Busan.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to investigate the perception of
      sugar reduction, nutrition education, and frequency of snacking in children
      according to the self-perceived dietary preferences for sweet taste by mothers in
      Busan. SUBJECTS/METHODS: A total of 277 mothers were surveyed, and their
      perceptions of sugar reduction and the frequency of snacking in children were
      assessed using a questionnaire. The subjects were classified into either a sweet
      (n = 91) or an unsweet (n = 186) group according to their self-perceived
      preferences for a sweet taste. RESULTS: In the sweet group, the results for sweet
      products were sweetened ice (86.8%), confectionery (74.7%), processed milk
      (73.6%), carbonated beverages (71.4%), and fermented milk (53.9%). In the unsweet
      group, the results were sweetened ice (88.7%), carbonated beverages (78.5%),
      processed milk (75.8%), confectionery (69.4%), and fermented milk (50.5%). The
      necessity of sugar intake reduction was high in both groups (sweet = 89.0%,
      unsweet = 82.8%). Beverage purchases after identifying the nutrition labeling was
      significantly lower in the sweet group than in the unsweet group (P < 0.05). The
      reasons for the beverage purchases instead of water were "habitually" (50.5%) and
      "like sweet taste" (25.3%) in the sweet group (P < 0.01). Snacking in children
      was significantly higher in the sweet group based on the increased frequencies of
      carbonated drinks (P < 0.01), fast food (P < 0.001), candy and chocolate (P <
      0.05), crackers (P < 0.01), ramen (P < 0.01), and fish paste/hotdogs (P < 0.01).
      The frequency of purchase education after identifying the nutrition labeling was
      significantly lower in the sweet group than in the unsweet group (P < 0.01).
      CONCLUSIONS: These findings suggest that a perception of sugar reduction and
      practical nutrition education aimed at reducing the sugar intake are necessary to
      improve dietary habits.

PMID- 27698964
TI  - Child health promotion program in South Korea in collaboration with US National
      Aeronautics and Space Administration: Improvement in dietary and nutrition
      knowledge of young children.
AB  - BACKGROUND/OBJECTIVES: Childhood obesity has become a global epidemic.
      Development of effective and sustainable programs to promote healthy behaviors
      from a young age is important. This study developed and tested an intervention
      program designed to promote healthy eating and physical activity among young
      children in South Korea by adaptation of the US National Aeronautics and Space
      Administration (NASA) Mission X (MX) Program. SUBJECTS/METHODS: The intervention
      program consisted of 4 weeks of fitness and 2 weeks of nutrition education. A
      sample of 104 subjects completed pre- and post-surveys on the Children's
      Nutrition Acknowledgement Test (NAT). Parents were asked for their children's
      characteristics and two 24-hour dietary records, the Nutrition Quotient (NQ) at
      baseline and a 6-week follow-up. Child weight status was assessed using Korean
      body mass index (BMI) percentiles. RESULTS: At baseline, 16.4% (boy: 15.4%; girl:
      19.2%) of subjects were overweight or obese (based on BMI>=85%tile). Fat
      consumption significantly decreased in normal BMI children (48.6 +/- 16.8 g at
      baseline to 41.9 +/- 18.1 g after intervention, P < 0.05); total NQ score
      significantly increased from 66.4 to 67.9 (P < 0.05); total NAT score
      significantly improved in normal BMI children (74.3 at baseline to 81.9 after the
      program), children being underweight (from 71.0 to 77.0), and overweight children
      (77.1 at baseline vs. 88.2 after intervention, P < 0.001). CONCLUSIONS: The 6
      week South Korean NASA MX project is feasible and shows favorable changes in
      eating behaviors and nutritional knowledge among young children.

PMID- 27698965
TI  - Diet and the Gut.

PMID- 27698968
TI  - Seroprevalence of Hepatitis E Virus in Iran: A Systematic Review and Meta
      analysis.
AB  - BACKGROUND Hepatitis E virus (HEV) is one of common causes of viral hepatitis
      worldwide with higher prevalence in tropical and subtropical regions. Although
      epidemics of HEV have been reported from Iran, there are variable reports of this
      infection out of epidemics from different parts of Iran. This study aimed to
      determine the seroprevalence of HEV in Iran. METHODS In this systematic review
      and meta-analysis we searched PubMed, Scopus, Science direct, Google Scholar,
      Scientific Information Databank (SID), IranMedex, and Magiran for all relevant
      studies published in either English or Persian languages, up to 2015. Pooled
      seroprevalence estimates with a DerSimonian-Laird random-effects model were
      calculated. Statistical heterogeneity among the included studies was evaluated by
      Cochrane Q statistic and I2. RESULTS 38 studies fulfilled the inclusion criteria
      compromising 18461 participants. The pooled seroprevalence rate of HEV in Iran
      was estimated about 10% (95% CI=0.09-0.12) with maximum and minimum of 46% (95 %
      CI=0.42-0.50), and 0.01% (95 % CI=0.000-0.002), respectively. CONCLUSION HEV is
      common in Iran although the prevalence is lower than some neighbor countries.

PMID- 27698967
TI  - The Effect of Probiotic Plus Prebiotic Supplementation on the Tolerance and
      Efficacy of Helicobacter Pylori Eradication Quadruple Therapy: a Randomized
      Prospective Double Blind Controlled Trial.
AB  - BACKGROUND Standard anti-Helicobacter pylori (H. pylori) treatment fails in the
      eradication of the organism in almost 10-35% of the patients and has different
      side effects. Recent studies have proposed that probiotic supplementations with
      or without prebiotic may improve the eradication rate and diminish the side
      effects, although it is still a controversial issue. We aimed to investigate the
      effect of probiotic with prebiotic supplementation on the eradication rate and
      side effects of anti H. pylori quadruple therapy. METHODS 76 patients with a
      positive biopsy specimen for H. pylori were enrolled. They were randomized to
      receive quadruple therapy of bismuth, clarithromycin, amoxicillin, and omeprazole
      for 14 days and also the synbiotic or the placebo. We asked them to answer study
      questionnaires at the beginning and during the treatment. Finally, urea breath
      test was done 8 weeks after the treatment. RESULTS The eradication rate was
      significantly better in the synbiotic group by intention-to-treat analysis
      (p<0.05). Treatment side effects such as diarrhea, nausea, vomiting, epigastric
      pain, flatulence, constipation, and taste abnormality were similar in both groups
      but anorexia was significantly better in the synbiotic group (p <0.05).
      CONCLUSION The eradication rate was significantly better in the synbiotic group
      by intention-to-treat analysis (p<0.05). Treatment side effects such as diarrhea,
      nausea, vomiting, epigastric pain, flatulence, but could improve the eradication
      by augmenting the treatment tolerance and compliance.

PMID- 27698969
TI  - Factors Associated with Outcome in Patients with Acute Upper Gastrointestinal
      Bleeding in a Tertiary Referral Center in Northern Iran.
AB  - BACKGROUND Upper gastrointestinal bleeding (UGIB) is a major healthcare problem
      and is the most frequent gastrointestinal reason for admission to hospital. We
      aimed to investigate the prognosis of patients with UGIB referred to a referral
      hospital in northern Iran in 2013. METHODS All patients with UGIB who admitted to
      Sayyad Shirazi Hospital, in Gorgan, northern Iran, in 2013 were enrolled. The
      patients' demographic data as well as data about admission, diseases, drug
      history, and patients' prognosis were collected by structured questionnaire using
      information in hospital files. The relationships between different factors with
      the proportion of mortality and recurrence were assessed using Chi-square test.
      RESULTS In total, 168 patients were enrolled of whom 109 (64.9%) were male. The
      mean (SD) age of the patients was 59.4 (18.2) years. Mortality and recurrence
      occurred in 23.2% and 34.5% of the subjects, respectively. We found significant
      relationships between older age and diagnosis of malignancy with mortality (p
      =0.03 and p <0.01) and recurrence (p<0.01 and p <0.01). CONCLUSION We found
      relatively high rates of mortality and recurrence among patients with UGIB. Our
      results suggested older age and diagnosis of malignancy as the most important
      indicators of mortality and recurrence in such patients. Considering these
      factors in clinical settings may result in better and more effective management
      of patients with UGIB.

PMID- 27698966
TI  - New Concepts on Pathogenesis and Diagnosis of Liver Fibrosis; A Review Article.
AB  - Liver fibrosis is a potentially reversible response to hepatic insults, triggered
      by different chronic diseases most importantly viral hepatitis, alcoholic, and
      nonalcoholic fatty liver disease. In the course of the chronic liver disease,
      hepatic fibrogenesis may develop, which is attributed to various types of cells,
      molecules, and pathways. Activated hepatic stellate cell (HSC), the primary
      source of extracellular matrix (ECM), is fundamental in pathophysiology of
      fibrogenesis, and thus is the most attractable target for reversing liver
      fibrosis. Although, liver biopsy has long been considered as the gold standard
      for diagnosis and staging of hepatic fibrosis, assessing progression and
      regression by biopsy is hampered by its limitations. We provide recent views on
      noninvasive approaches including serum biomarkers and radiologic techniques.

PMID- 27698970
TI  - Association between Pattern of Gastritis and Gastroesophageal Reflux Disease in
      Patients with Helicobacter Pylori Infection.
AB  - : BACKGROUND Reflux disease is a common gastrointestinal problem. The association
      between reflux disease and gastritis pattern is controversial. AIM: To determine
      the association between reflux disease and gastritis pattern in patients with
      Helicobacter pylori (H. pylori) infection. METHODS 470 patients with dyspepsia
      and reflux disease were enrolled in this study. The inclusion criteria were
      willing to participate in the study, age over 40 years, and having the criteria
      of ROME III for at least 3 months. Patients with history of H. pylori eradication
      therapy during the 3 months before the study, a history of gastric surgery, and
      gastric cancer were excluded. All of the participants underwent upper endoscopy
      and two biopsy samples were taken from antrum, body, and fundal areas. RESULTS H.
      pylori infection rate was 367 (78.1%) with mean age of 59.8 +/- 11.4 years. Of
      them 131 patients (35.7%) were male. Reflux disease was detected in 273 (74.4%)
      patients. 216 (58.9%) and 102 (27.8%) patients had non-erosive reflux disease
      (NERD) and gastroesophageal reflux disease (GERD), respectively. Corpus
      predominant and antral predominant gastritis were seen in 72 (19.6%) and 129
      (35.2%) patients, respectively. Antral gastritis was significantly associated
      with GERD (p<0.01). In regression analysis, antral predominant gastritis had a
      significant association with GERD (OR=1.92; 95%CI: 1.22- 3.12). The same result
      was observed in mild to moderate antral and greater curvature gastritis (OR=
      1.26; 95%CI: 0.25-6.40 and OR= 3.0; 95%CI: 0.63-14.17, respectively). CONCLUSION
      According to these finding ,we could suggest that the pattern of gastritis could
      be associated with reflux disease and GERD.

PMID- 27698972
TI  - A Comparison between Hybrid and Concomitant Regimens for Helicobacter Pylori
      Eradication: A Randomized Clinical Trial.
AB  - BACKGROUND Helicobacter pylori (H. pylori) is one of the most common bacterial
      infections worldwide. We designed a study to compare the efficacy of 14-day
      hybrid regimen with 10-day concomitant therapy for H. pylori eradication in Iran.
      METHODS 252 patients with naive H. pylori infection were randomly divided to
      receive either hybrid regimen (pantoprazole 40 mg, and amoxicillin 1 gr twice
      daily for 14 days, accompanied by clarithromycin 500 mg, and metronidazole 500
      mg, twice daily just during the last 7 days) or concomitant regimen (pantoprazole
      40 mg, amoxicillin 1 gr, clarithromycin 500 mg, and metronidazole 500 mg, all
      twice daily for 10 days). 8 weeks after therapy, 14C- urease breath test was
      performed to confirm eradication. RESULTS According to intention to treat
      analysis, the eradication rates were 87.3% (95% CI: 81.4-93.1) and 80.9% (95% CI:
      74-87.8) in hybrid and concomitant groups, respectively (p=0.38). Per-protocol
      eradication rates were 89.3% (95% CI: 83.8-94.7) and 83.1% (95% CI: 76.3-89.8),
      respectively (p=0.19). The rates of severe side effects were not statistically
      different between the two groups (4% vs. 8.7%). CONCLUSION 14-day hybrid therapy
      can be considered as a nearly acceptable regimen with few severe side effects in
      Iran. However, it seems that the efficacy of this therapy is decreasing as the
      resistance rates to antibiotics are increasing. We suggest further studies to
      assess the efficacy of a more prolonged concomitant therapy for H. pylori
      eradication in Iran.

PMID- 27698971
TI  - Accuracy of 99mTc (V)-Dimercaptosuccinic Acid Scintigraphy and Fecal Calprotectin
      Compared with Colonoscopy in Localizing Active Lesions in Inflammatory Bowel
      Disease.
AB  - INTRODUCTION Due to limitation of colonoscopy in assessing the entire bowel and
      patients' intolerance in inflammatory bowel disease (IBD), in the current study,
      we aimed to prospectively compare the accuracy of 99mTc(V)-dimercaptosuccinic
      acid (DMSA) and fecal calprotectin with ileocolonoscopy as new methods for
      localizing inflammations. METHODS Current prospective study conducted between
      2012 and 2014 on 30 patients with IBD attending Gastroenterology Clinic of Tehran
      University of Medical Sciences. Fecal calprotectin and disease activity were
      measured for all participants and all of them underwent 99mTc (V)-DMSA
      scintigraphy and colonoscopy. The accuracy of 99mTc (V)-DMSA scintigraphy and
      calprotectin in localizing bowel lesions were calculated. RESULTS A total of 22
      patients with ulcerative colitis (UC) and 8 patients with Crohn's disease (CD)
      were evaluated in our study. Sensitivity, positive likelihood ratio (PLR), and
      positive predictive value (PPV) of scintigraphy and calprotectin over colonoscopy
      in localization of UC lesions were 86.36%, 0.86%, 100.00% and 90.91%, 0.91, and
      100.00%, respectively. Meanwhile, it showed 66.67% sensitivity and 81.25%
      specificity with PLR=3.56, negative likelihood ratio (NLR)=0.41, PPV=84.21%, and
      negative predictive value (NPV)= 61.90% in localizing lesions in patients with
      CD. The calprotectin level had sensitivity, PLR, and PPV of 90.00%, 0.90, and
      100.00% in detecting active disease over colonoscopy, respectively. CONCLUSION
      The 99mTc (V)-DMSA scintigraphy would be an accurate method for detecting active
      inflammation in follow-up of patients with IBD and assessing response to
      treatment as a non-invasive and complementary method beside colonoscopy for more
      accurate diagnosis of CD or UC.

PMID- 27698973
TI  - Molecular and Immunohistochemical Study of Platelet Derived Growth Factor
      Receptor Alpha in KIT Negative Gastrointestinal Stromal Tumors; the First Report
      from Iran.
AB  - : BACKGROUND Gastrointestinal stromal tumors (GISTs) are potentially malignant
      tumors; however their behavior and response to treatment is dependent on the type
      of mutation and immunohistochemical expression of antigens. It is recommended to
      perform routine molecular and immunohistochemical tests in KIT and platelet
      derived growth factor receptor alpha (PDGFRA) molecules for making decision
      regarding targeted therapy and prediction of the behavior of the tumor.
      OBJECTIVES: There has been no study from Iran regarding the PDGFRA mutational
      analysis in GISTs. In this study, for the first time from Iran, we performed
      immunohistochemical and molecular analysis of PDGFRA molecule on GISTs. METHODS
      In a cross-sectional study during 7 years (2008-2014) on 50 untreated non
      recurrent non-metastatic newly diagnosed GISTs, molecular analysis and
      immunohistochemical staining for PDGFRA were performed and findings were compared
      with different clinicopathological characteristics.. RESULTS During the 7 years,
      50 cases of GISTs according to the above mentioned criteria were found. 17 cases
      were negative for KIT mutation. Of them, 15 (30%) were positive for either exon
      12 or 18 mutation of PDGFRA. These cases showed more epithelioid morphology and
      the number of mitotic figures were lower than PDFRA negative GISTs. Also
      according to the criteria for risk assessment, it seems that PDGFRA mutant GISTs
      are rarely in the high risk category. CONCLUSION PDGFRA mutant GISTs are common
      in Iranian population and it is recommended to perform mutation analysis for
      PDGFRA in every GIST with wild type KIT and epithelioid morphology.

PMID- 27698974
TI  - SpyGlass Pancreatoscopy and Successful Retrieval of a Proximally Migrated
      Pancreatic Stent; Unusual Case and Technical Tips.
AB  - Pancreatic stent proximal migration is a well known complication of pancreatic
      duct stenting, which occurs in about 5-6% of cases. Serious complications should
      be avoided by retrieval of the stent via different endoscopic techniques. We
      report a new technique previously reported only once (in a pancreatic duct with
      underlying pathology), to remove the proximally migrated pancreatic stent in a
      normal pancreatic duct by SpyGlass Direct Visualization System (Boston
      Scientific, Natick, Massachusetts, USA) and SpyBite Forceps (Boston Scientific,
      Natick, Massachusetts, USA).

PMID- 27698975
TI  - Upper Gastrointestinal Bleeding as the First Manifestation of Wegener's
      Granulomatosis.
AB  - Wegener's granulomatosis is an uncommon inflammatory disease that manifests as
      vasculitis, granulomatosis, and necrosis. It usually involves the upper and lower
      respiratory tracts and kidneys. Although it may essentially involve any organ,
      gastrointestinal (GI) involvement is notably uncommon. A 20-year-old male patient
      presented with epigastric pain, vomiting, hematemesis, and melena. On physical
      examination, he was pale. There was no abdominal tenderness or organomegaly.
      Upper GI endoscopy revealed dark blue-colored infiltrative lesions in prepyloric
      area. Evaluation of the biopsy sample showed mononuclear cell infiltration in the
      submucosal area, hyperplastic polyp, and chronic gastritis. High dose proton pump
      inhibitor and adjunctive supportive measures were given but no change in the
      follow-up endoscopy was detected. During hospital course, he developed
      intermittent fever and serum creatinine elevation. 12 days after admission, he
      developed dyspnea, tachypnea, and painful swelling of metacarpophalangeal joints,
      and maculopapular rash in extensor surface of the right forearm. Chest
      radiography showed pulmonary infiltration. Serum c-ANCA titer was strongly
      positive and skin biopsy revealed leukocytoclastic vasculitis. The patient
      received methylprednisolone pulse, which resulted in complete recovery of
      symptoms and gastric lesion. The present case indicates that GI bleeding may be
      the first manifestation of Wegener's granulomatosis. Moreover, it should be
      emphasized that gastric biopsy is not characteristic or diagnostic in such
      patients.

PMID- 27698976
TI  - Image Statistics and the Fine Lines of Material Perception.
AB  - We experience vivid percepts of objects and materials despite complexities in the
      way images are structured by the interaction of light with surface properties (3D
      shape, albedo, and gloss or specularity). Although the perception of gloss (and
      lightness) has been argued to depend on image statistics (e.g., sub-band skew),
      studies have shown that perceived gloss depends critically on the structure of
      luminance variations in images. Here, we found that separately adapting observers
      to either positive or negative skew generated declines in perceived gloss,
      contrary to the predictions of theories involving image statistics. We also found
      similar declines in perceived gloss following adaptation to contours
      geometrically correlated with sharp specular edges. We further found this
      aftereffect was stronger when contour adaptors were aligned with specular edges
      compared with adaptation to the same contours rotated by 90 degrees . These
      findings support the view that the perception of gloss depends critically on the
      visual system's ability to encode specular edge structure and not image skew.

PMID- 27698977
TI  - The Folded Paper Size Illusion: Evidence of Inability to Perceptually Integrate
      More Than One Geometrical Dimension.
AB  - The folded paper-size illusion is as easy to demonstrate as it is powerful in
      generating insights into perceptual processing: First take two A4 sheets of
      paper, one original sized, another halved by folding, then compare them in terms
      of area size by centering the halved sheet on the center of the original one! We
      perceive the larger sheet as far less than double (i.e., 100%) the size of the
      small one, typically only being about two thirds larger-this illusion is
      preserved by rotating the inner sheet and even by aligning it to one or two
      sides, but is dissolved by aligning both sheets to three sides, here documented
      by 88 participants' data. A potential explanation might be the general
      incapability of accurately comparing more than one geometrical dimension at once
      in everyday life, we solve this perceptual-cognitive bottleneck by reducing the
      complexity of such a task via aligning parts with same lengths.

PMID- 27698978
TI  - Do Individual Differences and Aging Effects in the Estimation of Geographical
      Slant Reflect Cognitive or Perceptual Effects?
AB  - Several individual differences including age have been suggested to affect the
      perception of slant. A cross-sectional study of outdoor hill estimation (N = 106)
      was analyzed using individual difference measures of age, experiential knowledge,
      fitness, personality traits, and sex. Of particular note, it was found that for
      participants who reported any experiential knowledge about slant, estimates
      decreased (i.e., became more accurate) as conscientiousness increased, suggesting
      that more conscientious individuals were more deliberate about taking their
      experiential knowledge (rather than perception) into account. Effects of fitness
      were limited to those without experiential knowledge, suggesting that they, too,
      may be cognitive rather than perceptual. The observed effects of age, which
      tended to produce lower, more accurate estimates of hill slant, provide more
      evidence that older adults do not see hills as steeper. The main effect of age
      was to lower slant estimates; such effects may be due to implicit experiential
      knowledge acquired over a lifetime. The results indicate the impact of cognitive,
      rather than perceptual factors on individual differences in slant estimation.

PMID- 27698979
TI  - Using Single Colors and Color Pairs to Communicate Basic Tastes.
AB  - Recently, it has been demonstrated that people associate each of the basic tastes
      (e.g., sweet, sour, bitter, and salty) with specific colors (e.g., red, green,
      black, and white). In the present study, we investigated whether pairs of colors
      (both associated with a particular taste or taste word) would give rise to
      stronger associations relative to pairs of colors that were associated with
      different tastes. We replicate the findings of previous studies highlighting the
      existence of a robust crossmodal correspondence between individual colors and
      basic tastes. However, while there was evidence that pairs of colors could indeed
      communicate taste information more consistently than single colors, our
      participants took more than twice as long to match the color pairs with tastes
      than the single colors. Possible reasons for these results are discussed.

PMID- 27698980
TI  - The Honeycomb illusion: Uniform textures not perceived as such.
AB  - We present a series of patterns, in which texture is perceived differently at
      fixation in comparison to the periphery, such that a physically uniform stimulus
      yields a nonuniform percept. We call this the Honeycomb illusion, and we discuss
      it in relation to the similar Extinction illusion (Ninio & Stevens, 2000). The
      effect remains strong despite multiple fixations, dynamic changes, and
      manipulations of the size of texture elements. We discuss the phenomenon in
      relation to how vision achieves a detailed and stable representation of the
      environment despite changes in retinal spatial resolution and dramatic changes
      across saccades. The Honeycomb illusion complements previous related observations
      in suggesting that this representation is not necessarily based on multiple
      fixations (i.e., memory) or on extrapolation from information available to
      central vision.

PMID- 27698981
TI  - The Perceived Size and Shape of Objects in Peripheral Vision.
AB  - Little is known about how we perceive the size and shape of objects in far
      peripheral vision. Observations made during an artistic study of visual space
      suggest that objects appear smaller and compressed in the periphery compared with
      central vision. To test this, we conducted three experiments. In Experiment 1, we
      asked participants to draw how a set of peripheral discs appeared when viewed
      peripherally without time or eye movement constraints. In Experiment 2, we used
      the method of constant stimuli to measure when a briefly presented peripheral
      stimulus appeared bigger or smaller compared with a central fixated one. In
      Experiment 3, we measured how accurate participants were in discriminating shapes
      presented briefly in the periphery. In Experiment 1, the peripheral discs were
      reported as appearing significantly smaller than the central disc, and as having
      an elliptical or polygonal contour. In Experiment 2, participants judged the size
      of peripheral discs as being significantly smaller when compared with the central
      disc across most of the peripheral field, and in Experiment 3, participants were
      quite accurate in reporting the shape of the peripheral object, except in the far
      periphery. Our results show that objects in the visual periphery are perceived as
      diminished in size when presented for long and brief exposures, suggesting
      diminution is an intrinsic feature of the structure of the visual space. Shape
      distortions, however, are reported only with longer exposures.

PMID- 27698983
TI  - Equidistant Intervals in Perspective Photographs and Paintings.
AB  - Human vision is extremely sensitive to equidistance of spatial intervals in the
      frontal plane. Thresholds for spatial equidistance have been extensively measured
      in bisecting tasks. Despite the vast number of studies, the informational basis
      for equidistance perception is unknown. There are three possible sources of
      information for spatial equidistance in pictures, namely, distances in the
      picture plane, in physical space, and visual space. For each source, equidistant
      intervals were computed for perspective photographs of walls and canals.
      Intervals appear equidistant if equidistance is defined in visual space.
      Equidistance was further investigated in paintings of perspective scenes. In
      appraisals of the perspective skill of painters, emphasis has been on accurate
      use of vanishing points. The current study investigated the skill of painters to
      depict equidistant intervals. Depicted rows of equidistant columns, tiles,
      tapestries, or trees were analyzed in 30 paintings and engravings. Computational
      analysis shows that from the middle ages until now, artists either represented
      equidistance in physical space or in a visual space of very limited depth. Among
      the painters and engravers who depict equidistance in a highly nonveridical
      visual space are renowned experts of linear perspective.

PMID- 27698982
TI  - Relative Visual Oscillation Can Facilitate Visually Induced Self-Motion
      Perception.
AB  - Adding simulated viewpoint jitter or oscillation to displays enhances visually
      induced illusions of self-motion (vection). The cause of this enhancement is yet
      to be fully understood. Here, we conducted psychophysical experiments to
      investigate the effects of different types of simulated oscillation on vertical
      vection. Observers viewed horizontally oscillating and nonoscillating optic flow
      fields simulating downward self-motion through an aperture. The aperture was
      visually simulated to be nearer to the observer and was stationary or oscillating
      in-phase or counter-phase to the direction of background horizontal oscillations
      of optic flow. Results showed that vection strength was modulated by the
      oscillation of the aperture relative to the background optic flow. Vertical
      vection strength increased as the relative oscillatory horizontal motion between
      the flow and the aperture increased. However, such increases in vection were only
      generated when the added oscillations were orthogonal to the principal direction
      of the optic flow pattern, and not when they occurred in the same direction. The
      oscillation effects observed in this investigation could not be explained by
      motion adaptation or different (motion parallax based) effects on depth
      perception. Instead, these results suggest that the oscillation advantage for
      vection depends on relative visual motion.

PMID- 27698984
TI  - How Beauty Determines Gaze! Facial Attractiveness and Gaze Duration in Images of
      Real World Scenes.
AB  - We showed that the looking time spent on faces is a valid covariate of beauty by
      testing the relation between facial attractiveness and gaze behavior. We
      presented natural scenes which always pictured two people, encompassing a wide
      range of facial attractiveness. Employing measurements of eye movements in a free
      viewing paradigm, we found a linear relation between facial attractiveness and
      gaze behavior: The more attractive the face, the longer and the more often it was
      looked at. In line with evolutionary approaches, the positive relation was
      particularly pronounced when participants viewed other sex faces.

PMID- 27698985
TI  - Touching and Hearing Unseen Objects: Multisensory Effects on Scene Recognition.
AB  - In three experiments, we investigated the influence of object-specific sounds on
      haptic scene recognition without vision. Blindfolded participants had to
      recognize, through touch, spatial scenes comprising six objects that were placed
      on a round platform. Critically, in half of the trials, object-specific sounds
      were played when objects were touched (bimodal condition), while sounds were
      turned off in the other half of the trials (unimodal condition). After first
      exploring the scene, two objects were swapped and the task was to report, which
      of the objects swapped positions. In Experiment 1, geometrical objects and simple
      sounds were used, while in Experiment 2, the objects comprised toy animals that
      were matched with semantically compatible animal sounds. In Experiment 3, we
      replicated Experiment 1, but now a tactile-auditory object identification task
      preceded the experiment in which the participants learned to identify the objects
      based on tactile and auditory input. For each experiment, the results revealed a
      significant performance increase only after the switch from bimodal to unimodal.
      Thus, it appears that the release of bimodal identification, from audio-tactile
      to tactile-only produces a benefit that is not achieved when having the reversed
      order in which sound was added after having experience with haptic-only. We
      conclude that task-related factors other than mere bimodal identification cause
      the facilitation when switching from bimodal to unimodal conditions.

PMID- 27698987
TI  - New Insights Into the Evolution of Color Terms or an Effect of Saturation?
AB  - Through their thorough investigation of the Hadza, a nonindustrialized language
      community in Tanzania, Lindsey and colleagues (2015) developed a new approach to
      understand the evolution of color terms. In the present commentary, I discuss the
      possibility that some of their results might be explained by the lacking control
      of saturation of their color stimuli. The saturation of colors plays an important
      yet widely neglected role in color naming. The additional analyses presented here
      suggest that the results on Hadzane color naming could be due to variations in
      saturation in the stimulus set rather than being evidence for universal
      constraints on color term evolution.

PMID- 27698986
TI  - Explicit Associative Learning and Memory in Synesthetes and Nonsynesthetes.
AB  - Most current theories regarding the development of synesthesia focus on cross
      modal neural connections and genetic underpinnings, but recent evidence has
      revitalized the potential role of associative learning. In the present study, we
      compared synesthetes' and controls' ability to explicitly learn shape-color
      pairings. Using a continuous measure of accuracy and multiple testing blocks, we
      found that synesthetes learned these pairings faster than controls. In a delayed
      retest, synesthetes outperformed controls, demonstrating enhanced long-term
      memory for shape-color associations. Following this retest, participants learned
      shuffled associations, and we found little evidence for group differences in
      subsequent learning ability. Overall, our findings support the hypothesis that
      synesthetes have exceptional associative learning abilities and further specify
      that this advantage pertains to the initial learning rate and long-term retention
      of associations.

PMID- 27698988
TI  - An Easy Way to Show Memory Color Effects.
AB  - This study proposes and evaluates a simple stimulus display that allows one to
      measure memory color effects (the effect of object knowledge and memory on color
      perception). The proposed approach is fast and easy and does not require running
      an extensive experiment. It shows that memory color effects are robust to minor
      variations due to a lack of color calibration.

PMID- 27698989
TI  - Rotating Squares Look Like Pincushions.
AB  - Rotating squares appeared to be distorted into pincushions with concave sides.
      These illusory shape changes were caused by a perceived compression along the
      curved path of motion.

PMID- 27698990
TI  - Pot/Lid Illusion.
AB  - A new everyday visual size illusion is presented-the Pot/Lid illusion. Observers
      choose an unduly large lid for a pot. We ask whether the optic slant of the pot
      brim would increase its apparent size or if vision underestimates the size of
      tilted lids.

PMID- 27698992
TI  - Motion-Driven Transparency and Opacity.
AB  - When two adjacent surfaces move in step, this can generate a sensation of
      transparency, even in the absence of intersections. Stopping the motion of one
      surface makes it look suddenly opaque.

PMID- 27698993
TI  - Detection of Sound Image Movement During Horizontal Head Rotation.
AB  - Movement detection for a virtual sound source was measured during the listener's
      horizontal head rotation. Listeners were instructed to do head rotation at a
      given speed. A trial consisted of two intervals. During an interval, a virtual
      sound source was presented 60 degrees  to the right or left of the listener, who
      was instructed to rotate the head to face the sound image position. Then in one
      of a pair of intervals, the sound position was moved slightly in the middle of
      the rotation. Listeners were asked to judge the interval in a trial during which
      the sound stimuli moved. Results suggest that detection thresholds are higher
      when listeners do head rotation. Moreover, this effect was found to be
      independent of the rotation velocity.

PMID- 27698991
TI  - Early Visual Perception Potentiated by Object Affordances: Evidence From a
      Temporal Order Judgment Task.
AB  - Perceived objects automatically potentiate afforded action. Object affordances
      also facilitate perception of such objects, and this occurrence is known as the
      affordance effect. This study examined whether object affordances facilitate the
      initial visual processing stage, or perceptual entry processes, using the
      temporal order judgment task. The onset of the graspable (right-handled) coffee
      cup was perceived earlier than that of the less graspable (left-handled) cup for
      right-handed participants. The affordance effect was eliminated when the coffee
      cups were inverted, which presumably conveyed less affordance information. These
      results suggest that objects preattentively potentiate the perceptual entry
      processes in response to their affordances.

PMID- 27698994
TI  - Matching the Material of Transparent Objects: The Role of Background Distortions.
AB  - It has been proposed that the visual system is able to estimate the refractive
      index of thick transparent objects from background distortions caused by them.
      More specifically, it was hypothesized that this is done based on a mid-level
      cue, the distortion field, whose computation from the input requires comparing
      the part of the background seen through the object with the part visible in plain
      view. We test two predictions derived from this hypothesis: (a) scene variables
      that do not change the distortion field, for instance, the density of the
      background texture, should not systematically influence the subjects' settings in
      a material matching task. (b) The uncertainty of the estimates should increase
      sharply, if the part of the background texture in plain view is removed. Our
      results are not compatible with these two predictions but are completely in line
      with the alternative interpretation that the subjects maximized the similarity of
      the distorted background textures on the image level. Additional results indicate
      that subjects can take relations between the distorted and the undistorted
      background into account if this is encouraged by the experimental design, but
      they do this in a simplistic way that is inappropriate to estimate the refractive
      index.

PMID- 27635226
TI  - Multi-site tumor sampling (MSTS) improves the performance of histological
      detection of intratumor heterogeneity in clear cell renal cell carcinoma (CCRCC).
AB  - Current standard-of-care tumor sampling protocols for CCRCC (and other cancers)
      are not efficient at detecting intratumoural heterogeneity (ITH). We have
      demonstrated in silico that an alternative protocol, multi-site tumor sampling
      (MSTS) based upon the divide and conquer (DAC) algorithm, can significantly
      increase the efficiency of ITH detection without extra costs. Now we test this
      protocol on routine hematoxylin-eosin (HE) sections in a series of 38 CCRCC
      cases. MSTS was found to outperform traditional sampling when detecting either
      high grade (p=0.0136) or granular/eosinophilic cells (p=0.0114). We therefore
      propose that MSTS should be used in routine clinical practice.

PMID- 27540468
TI  - Computational analysis of perturbations in the post-fusion Dengue virus envelope
      protein highlights known epitopes and conserved residues in the Zika virus.
AB  - The dramatic transformation of the Zika virus (ZIKV) from a relatively unknown
      virus to a pathogen generating global-wide panic has exposed the dearth of
      detailed knowledge about this virus. Decades of research in the related Dengue
      virus (DENV), finally culminating in a vaccine registered for use in endemic
      regions (CYD-TDV) in three countries, provides key insights in developing
      strategies for tackling ZIKV, which has caused global panic to microcephaly and
      Guillain-Barre Syndrome. Dengue virus (DENV), a member of the family
      Flaviviridae, the causal agent of the self-limiting Dengue fever and the
      potentially fatal hemorrhagic fever/dengue shock syndrome, has been a scourge in
      tropical countries for many centuries. The recently solved structure of mature
      ZIKV (PDB ID:5IRE) has provided key insights into the structure of the envelope
      (E) and membrane (M) proteins, the primary target of neutralizing antibodies. The
      previously established MEPP methodology compares two conformations of the same
      protein and identifies residues with significant spatial and electrostatic
      perturbations. In the current work, MEPP analyzed the pre-and post-fusion DENV
      type 2 envelope (E) protein, and identified several known epitopes (His317,
      Tyr299, Glu26, Arg188, etc.) (MEPPitope). These residues are overwhelmingly
      conserved in ZIKV and all DENV serotypes, and also enumerates residue pairs that
      undergo significant polarity reversal. Characterization of alpha-helices in E
      proteins show that alpha1 is not conserved in the sequence space of ZIKV and
      DENV. Furthermore, perturbation of alpha1 in the post-fusion DENV structure
      includes a known epitope Asp215, a residue absent in the pre-fusion alpha1. A
      cationic beta-sheet in the GAG-binding domain that is stereochemically equivalent
      in ZIKV and all DENV serotypes is also highlighted due to a residue pair (Arg286
      Arg288) that has a significant electrostatic polarity reversal upon fusion.
      Finally, two highly conserved residues (Thr32 and Thr40), with little emphasis in
      existing literature, are found to have significant electrostatic perturbation.
      Thus, a combination of different computational methods enable the rapid and
      rational detection of critical residues as epitopes in the search for an elusive
      therapy or vaccine that neutralizes multiple members of the Flaviviridae family.
      These secondary structures are conserved in the related Dengue virus (DENV), and
      possibly rationalize isolation techniques particle adsorption on magnetic beads
      coated with anionic polymers and anionic antiviral agents (viprolaxikine) for
      DENV. These amphipathic alpha-helices could enable design of molecules for
      inhibiting alpha-helix mediated protein-protein interactions. Finally, comparison
      of these secondary structures in proteins from related families illuminate subtle
      changes in the proteins that might render them ineffective to previously
      successful drugs and vaccines, which are difficult to identify by a simple
      sequence or structural alignment. Finally, conflicting results about residues
      that are involved in neutralizing a DENV-E protein by the potent antibody 5J7
      (PDB ID:3J6U) are reported.

PMID- 27698997
TI  - Social autopsy of neonatal mortality suggests needed improvements in maternal and
      neonatal interventions in Balaka and Salima districts of Malawi.
AB  - BACKGROUND: The Every Newborn Action Plan calls for reducing the neonatal
      mortality rates to fewer than 10 deaths per 1000 live births in all countries by
      2035. The current study aims to increase our understanding of the social and
      modifiable factors that can be addressed or reinforced to improve and accelerate
      the decline in neonatal mortality in Malawi. METHODS: The data come from the 2013
      Verbal and Social Autopsy (VASA) study that collected data in order to describe
      the biological causes and the social determinants of deaths of children under 5
      years of age in Balaka and Salima districts of Malawi. This paper analyses the
      social autopsy data of the neonatal deaths and presents results of a review of
      the coverage of key interventions along the continuum of normal maternal and
      newborn care and the description of breakdowns in the care provided for neonatal
      illnesses within the Pathway to Survival framework. RESULTS: A total of 320
      neonatal deaths were confirmed from the VASA survey. While one antenatal care
      (ANC) visit was high at 94%, the recommended four ANC visits was much lower at
      41% and just 17% of the mothers had their urines tested during the pregnancy. 173
      (54%) mothers of the deceased newborns had at least one labor/delivery
      complication that began at home. The caregivers of 65% (n = 75) of the 180
      newborns that were born at home or born and left a health facility alive
      perceived them to be severely ill at the onset of their illness, yet only 44% (n
      = 80) attempted and 36% (n = 65)could reach the first health provider after an
      average of 91 minutes travel time. Distance, lack of transport and cost emerged
      as the most important constraints to formal care-seeking during delivery and
      during the newborn fatal illness. CONCLUSIONS: This study suggests that maternal
      and neonatal health organizations and the local government of Malawi should
      increase the demand for key maternal and child health interventions, including
      the recommended 4 ANC visits, and ensure urine screening for all pregnant women.
      Early recognition and referrals of women with obstetric complications and
      interventions to promote maternal recognition of neonatal illnesses and care
      seeking before the child becomes severely ill are also needed to improve newborn
      survival in Balaka and Salima districts of Malawi.

PMID- 27698998
TI  - Self-reported diabetes education among Chinese middle-aged and older adults with
      diabetes.
AB  - BACKGROUND: To compare self-reported diabetes education among Chinese middle-aged
      and older adults with diabetes in three population groups: urban residents,
      migrants in urban settings, and rural residents. METHODS: We used data from the
      2011 China Health and Retirement Longitudinal Study. The sample included 993
      participants age 45 and older who reported having diabetes diagnosed from a
      health professional. We performed multilevel regressions performed to examine the
      associations between characteristics and different aspects of diabetes education
      received. FINDINGS: Our study shows that 20.24% of the participants received no
      diabetes education at all. Among those who received information, 46.82% of
      respondents with diabetes received weight control advice from a health care
      provider, 90.97% received advice on exercise, 60.37% received diet advice, 35.12%
      were spoken to smoking control, and only 17.89% of persons were informed of foot
      care. After controlling socioeconomic factors, life style, number of
      comorbidities and community factors, we found that compared with migrant
      population and rural residents, urban residents were more likely to receive
      diabetes education on diet. Urban residents were also more likely to obtain
      diabetes education and more aspects of diabetes education comparison with
      migrants and rural residents. CONCLUSIONS: Our study suggests diabetes education
      is a serious concern in China, and a significant proportion of the participants
      did not receive advice on smoking control and foot care. Rural residents and
      migrants from rural areas received much less diabetes education compared with
      urban residents. Efforts to improve diabetes educations are urgently needed in
      China.

PMID- 27698999
TI  - Population-level effectiveness of PMTCT Option A on early mother-to-child (MTCT)
      transmission of HIV in South Africa: implications for eliminating MTCT.
AB  - BACKGROUND: Eliminating mother-to-child transmission of HIV (EMTCT), defined as
      <=50 infant HIV infections per 100 000 live births, is a global priority. Since
      2011 policies to prevent mother-to-child transmission of HIV (PMTCT) shifted from
      maternal antiretroviral (ARV) treatment or prophylaxis contingent on CD4 cell
      count to lifelong maternal ARV treatment (cART). We sought to measure progress
      with early (4-8 weeks postpartum) MTCT prevention and elimination, 2011-2013, at
      national and sub-national levels in South Africa, a high antenatal HIV prevalence
      setting ( ~ 29%), where early MTCT was 3.5% in 2010. METHODS: Two surveys were
      conducted (August 2011-March 2012 and October 2012-May 2013), in 580 health
      facilities, randomly selected after two-stage probability proportional to size
      sampling of facilities (the primary sampling unit), to provide valid national and
      sub-national-(provincial)-level estimates. Data collectors interviewed caregivers
      of eligible infants, reviewed patient-held charts, and collected infant dried
      blood spots (iDBS). Confirmed positive HIV enzyme immunoassay (EIA) and positive
      total HIV nucleic acid polymerase chain reaction (PCR) indicated infant HIV
      exposure or infection, respectively. Weighted survey analysis was conducted for
      each survey and for the pooled data. FINDINGS: National data from 10 106 and 9120
      participants were analyzed (2011-12 and 2012-13 surveys respectively). Infant HIV
      exposure was 32.2% (95% confidence interval (CI) 30.7-33.6%), in 2011-12 and
      33.1% (95% CI 31.8-34.4%), provincial range of 22.1-43.6% in 2012-13. MTCT was
      2.7% (95% CI 2.1%-3.2%) in 2011-12 and 2.6% (95% CI 2.0-3.2%), provincial range
      of 1.9-5.4% in 2012-13. HIV-infected ARV-exposed mothers had significantly lower
      unadjusted early MTCT (2.0% [2011-12: 1.6-2.5%; 2012-13:1.5-2.6%]) compared to
      HIV-infected ARV-naive mothers [10.2% in 2011-12 (6.5-13.8%); 9.2% in 2012-13
      (5.6-12.7%)]. Pooled analyses demonstrated significantly lower early MTCT among
      exclusive breastfeeding (EBF) mothers receiving >10 weeks ARV prophylaxis or cART
      compared with EBF and no ARVs: (2.2% [95% CI 1.25-3.09%] vs 12.2% [95% CI 4.7
      19.6%], respectively); among HIV-infected ARV-exposed mothers, 24.9% (95% CI 23.5
      26.3%) initiated cART during or before the first trimester, and their early MTCT
      was 1.2% (95% CI 0.6-1.7%). Extrapolating these data, assuming 32% EIA positivity
      and 2.6% or 1.2% MTCT, 832 and 384 infants per 100 000 live births were HIV
      infected, respectively. CONCLUSIONS: Although we demonstrate sustained national
      level PMTCT impact in a high HIV prevalence setting, results are far-removed from
      EMTCT targets. Reducing maternal HIV prevalence and treating all maternal HIV
      infection early are critical for further progress.

PMID- 27699000
TI  - Caregiver perceptions and utilization of oral rehydration solution and other
      treatments for diarrhea among young children in Burkina Faso.
AB  - BACKGROUND: More than 500 000 young children die from dehydration caused by
      severe diarrhea each year, globally. Although routine use of oral rehydration
      solution (ORS) could prevent almost all of these deaths, ORS utilization remains
      low in many low-income countries. Previous research has suggested that
      misperceptions among caregivers may be an obstacle to wider use of ORS. METHODS:
      To better understand the extent of ORS utilization and the reasons for use or non
      use in low-resource settings, the project team conducted a semi-structured,
      quantitative survey of 400 caregivers in Burkina Faso in 2014. All caregivers had
      a child below the age of five who had diarrhea lasting 2 days or more in the
      previous 2 months. RESULTS: Although more than 80% of caregivers were aware of
      ORS, less than half reported using it to treat their child's diarrhea. Replacing
      fluids lost due to diarrhea was considered a low priority by most caregivers, and
      many said they considered antibiotics more effective for treating diarrhea. Users
      and non-users of ORS held substantially different perceptions of the product,
      though all caregivers tended to follow recommendations of health care workers. A
      significant proportion of users reported difficulty in getting a child to drink
      ORS. Costs and access to ORS were not found to be significant barriers to use.
      CONCLUSIONS: Misperceptions among caregivers and health workers contribute to low
      utilization of ORS. Better caregiver understanding of diarrheal disease and the
      importance of rehydration, as well as increased recommendation by health workers,
      will help to increase ORS utilization. Improving product presentation and taste
      will also help to increase use.

PMID- 27699001
TI  - A study assessing postoperative Corrugate Rubber drain of perianal abscess.
AB  - BACKGROUND: Perianal abscess which can lead to a devastating complications. The
      management of perianal abscess involves incision and drainage by different
      methods one of them is packing the cavity. AIM OF THE STUDY: The aim is using
      Corrugate Rubber drain as an alternative to other methods. PATIENTS AND METHODS:
      This study was an observational retrospective review of 137 'case series' of
      patients with perianal abscess over a fifteen-year period from January 2000 to
      December 2015. 67 patients in group A were managed by Corrugated Rubber drain and
      70 patients in group B were managed by packing. In group A, males were 92.53%
      more than females (7.46%) while group B, males were 85.71% and the rest were
      females. Outcome measures were assessed; time to cavity healing, pain scoring,
      abscess recurrence, fistula formation, analgesic requirement and skin
      disfigurement. RESULTS: The mean time of abscess healing in group A and B were
      8.50 +/- 0.49 and 8.90 +/- 0.23 days respectively. Their pain score using
      Corrugate Rubber drain postoperative were 2/10 in group A while group B was 8/10.
      Most of patients in group A needed mild analgesia (52/67) (77.61%). The rate of
      abscess recurrence and fistula development were (22/67) (32.83%) and (21/67)
      (31.34%) respectively in group A which is significantly lower than group B.
      CONCLUSIONS: Management of perianal abscess using Corrugate Rubber drain in
      compares with packing leads to immediate pain relief, low recurrence rate of
      abscess and fistula formation, without need to expert nursing and less ugly scar
      formation. This resulted in low morbidity and cost.

PMID- 27699002
TI  - The impact of temporal artery biopsy on surgical practice.
AB  - BACKGROUND: Giant cell arteritis (GCA) has the potential to cause irreversible
      blindness and stroke in affected patients [1-4]. Temporal artery biopsy (TAB)
      remains the gold standard test for GCA [6-8]. Recent literature suggests that TAB
      does not change management of patients with suspected GCA and that ultrasound
      scan (USS) may be sufficient enough alone to confirm the diagnosis [9-11,13]. The
      aim of this study is to therefore determine the impact of TAB on current surgical
      practice and emergency theatre services. MATERIALS AND METHODS: A retrospective
      clinical study was performed of patients who had undergone TAB at the Caboolture
      Hospital from January 2010 to September 2015. Demographic and clinical data was
      collected from patient's medical records in regards to GCA. RESULTS: A total of
      55 TAB were performed on 50 patients. Only two TAB were positive for GCA. Thirty
      eight (76%) patients had a pre-TAB ACR criteria score of >=3. Pre-operative
      corticosteroids were administered in forty-five (90%) patients, on average 4 +/-
      10 days pre-TAB. Mean time to TAB was 1.6 +/- 1.6 days following their booking.
      Ninety-one percent of TAB were performed by surgical registrars. All TAB were
      performed using local anaesthesia alone. CONCLUSIONS: TAB is an expensive
      procedure with a low positive yield. Recent evidence suggests promising results
      with USS in diagnosing GCA. With the exceedingly low positive TAB results found
      in this study, patients with suspected GCA should be investigated in accordance
      with the above algorithm. The routine use of USS will reduce the number of
      negative TAB performed.

PMID- 27699003
TI  - Using electronic health record collected clinical variables to predict medical
      intensive care unit mortality.
AB  - BACKGROUND: Clinical decision support systems are used to help predict patient
      stability and mortality in the Intensive Care Unit (ICU). Accurate patient
      information can assist clinicians with patient management and in allocating
      finite resources. However, systems currently in common use have limited
      predictive value in the clinical setting. The increasing availability of
      Electronic Health Records (EHR) provides an opportunity to use medical
      information for more accurate patient stability and mortality prediction in the
      ICU. OBJECTIVE: Develop and evaluate an algorithm which more accurately predicts
      patient mortality in the ICU, using the correlations between widely available
      clinical variables from the EHR. METHODS: We have developed an algorithm,
      AutoTriage, which uses eight common clinical variables from the EHR to assign
      patient mortality risk scores. Each clinical variable produces a subscore, and
      combinations of two or three discretized clinical variables also produce
      subscores. A combination of weighted subscores produces the overall score. We
      validated the performance of this algorithm in a retrospective study on the MIMIC
      III medical ICU dataset. RESULTS: AutoTriage 12 h mortality prediction yields an
      Area Under Receiver Operating Characteristic value of 0.88 (95% confidence
      interval 0.86 to 0.88). At a sensitivity of 80%, AutoTriage maintains a
      specificity of 81% with a diagnostic odds ratio of 16.26. CONCLUSIONS: Through
      the multidimensional analysis of the correlations between eight common clinical
      variables, AutoTriage provides an improvement in the specificity and sensitivity
      of patient mortality prediction over existing prediction methods.

PMID- 27699006
TI  - Spiritual leadership at the workplace: Perspectives and theories.
AB  - Leadership has always been an area of interest since time immemorial.
      Nevertheless, scientific theories regarding leadership started to appear only
      from the beginning of the 20th century. Modern theories of leadership such as
      strategic leadership theory emerged as early as the 1980s when outdated theories
      of behavioral contingency were questioned, resulting in the beginning of a shift
      in focus leading to the emergence of modern theories hypothesizing the importance
      of vision, motivation and value-based control of clan and culture. Value-driven
      clan control emphasizes the importance of the role played by employees in a
      rapidly changing work environment. Therefore, the 21st century marked the rise of
      the need to establish a culture driven by values, inspiring the workforce to
      struggle and strongly seek a shared vision. This can be accomplished by an
      effective and motivating leadership.

PMID- 27699004
TI  - Emerging role of microRNA-21 in cancer.
AB  - MicroRNAs (miRs) are a class of single-stranded RNA molecules of 15-27
      nucleotides in length that regulate gene expression at the post-translational
      level. miR-21 is one of the earliest identified cancer-promoting 'oncomiRs',
      targeting numerous tumor suppressor genes associated with proliferation,
      apoptosis and invasion. The regulation of miR-21 and its role in carcinogenesis
      have been extensively investigated. Recent studies have focused on the diagnostic
      and prognostic value of miR-21 as well as its implication in the drug resistance
      of human malignancies. The further use of miR-21 as a biomarker and target for
      cancer treatments is likely to improve the outcome for patients with cancer. The
      present review highlights recent findings associated with the importance of miR
      21 in hematological and non-hematological malignancies.

PMID- 27699005
TI  - Calprotectin as a diagnostic tool for inflammatory bowel diseases.
AB  - Inflammatory bowel diseases (IBD) are chronic intestinal disorders caused by a
      number of factors, including external influences, intestinal microbiota and
      genetics. The two major clinically defined types of IBD are Crohn's disease and
      ulcerative colitis, each of which is characterized by relapses in the clinical
      course, thus patients must be under constant observation via regular endoscopies.
      As endoscopy, which has been used for direct evaluation and diagnosis of IBD,
      requires uncomfortable and expensive bowel preparation, a non-invasive test was
      required to reduce the number of patients undergoing unnecessary endoscopy.
      Calprotectin is a protein occurring in the cytosol of inflammatory cells and is
      released by the activation of leukocytes. As it is elevated and stable in the
      faeces of patients with IBD and can be reliably detected in faecal samples of <5
      g, it may serve as an inexpensive, non-invasive diagnostic method for IBD. This
      is explored in the following review.

PMID- 27699007
TI  - Effects of antiepileptic drugs on the serum folate and vitamin B12 in various
      epileptic patients.
AB  - Epilepsy is a common neurodegenerative disease with an increasing morbidity.
      Clinical treatment of epilepsy includes symptomatic treatment, etiological
      treatment, surgery and prevention. The aim of the present study was to determine
      the effects of antiepileptic drugs (AEDs) on serum folate and vitamin B12 in
      various epileptic patients, and to examine the correlation between these effects
      and secondary cerebrovascular events. A total of 68 epileptic patients, diagnosed
      between May 2012 and May 2014, were included in the present study. The study
      included 8 cases of autonomic seizures, 10 cases of absence seizures, 13 cases of
      complex partial seizures, 28 cases of generalized tonic-clonic seizures, and 9
      cases of simple partial seizures. The patients received appropriate AED treatment
      according to the characteristics of epileptic seizure and the treatment guidance.
      The differences in the serum levels of folate and vitamin B12 in these patients,
      and the differences in the secondary cerebrovascular events in these patients
      after 1 year follow-up were analyzed. The difference in the AEDs used by various
      epileptic patients was statistically significant (P<0.05). The proportion of AED
      monotherapy in the autonomic seizure group and petit mal group was highest, and
      the proportion of two AED in combination with the psychomotor seizure, grand mal
      and simple partial seizure groups was highest. The serum levels of folate and
      vitamin B12 in these patients following treatment were significantly lower than
      those prior to treatment (P<0.05). The differences in the serum levels of folate
      and vitamin B12 in these groups following treatment were not statistically
      significant (P>0.05). The difference in the incidence of cerebrovascular events
      in these groups at follow up was not statistically significant (P>0.05). The
      multifactorial logistic regression analysis revealed that the serum levels of
      folate and vitamin B12 were the independent risk factors for epilepsy with
      secondary cerebrovascular events [folate: odds ratio (OR)=0.536, P=0.039;
      vitamin: OR=0.382, P=0.041]. In conclusion, various AEDs may decrease the serum
      levels of folate and vitamin B12 and affect the secondary cerebrovascular events
      in various epileptic patients. Thus, regular supplementation of folate and
      vitamin B12 may be an option.

PMID- 27699008
TI  - Comparison of gene expression profiles in aortic dissection and normal human
      aortic tissues.
AB  - The aim of the present study was to compare the gene expression profiles in
      aortic dissection (AD) and healthy human aortic tissue samples by DNA microarray
      analysis in order to screen the differential genes. In total, five AD and four
      healthy aortic specimens were selected; the total RNA was extracted and reverse
      transcribed into cDNA and in vitro transcribed into aRNA, followed by microarray
      hybridization for analysis. Thereafter, the transcription levels of six
      differential genes, myosin light chain kinase (MYLK), polycystin 1, transient
      receptor potential channel interacting (PKD-1), myosin heavy chain 11 (MYH11),
      superoxide dismutase 3, extracellular (SOD3), filamin A (FLNA), and transgelin
      (TAGLN), screened from the expression profiles were quantitatively verified.
      Compared with the healthy aortic specimens, a total of 1,661 genes in the AD
      group demonstrated more than 2-fold differential expression, of which 997 genes
      were upregulated and 664 genes were downregulated. Thereafter, six AD-associated
      genes that showed downregulation in the microarray assay were selected for
      quantitatively verifying the gene transcription level using reverse transcription
      quantitative polymerase chain reaction (RT-qPCR), which confirmed their
      downregulation compared with the healthy aortic tissue genes; of the six genes,
      the expression levels of MYLK, PKD-1, MYH11, SOD3 and TAGLN were significantly
      downregulated (P<0.05), while the expression of FLNA was not significantly
      downregulated (P>0.05). Thus, whole genome microarray may be used to screen
      differentially expressed genes between AD and healthy aortic tissues. When used
      in combination with RT-qPCR validation, this method may provide novel strategies
      for investigating AD.

PMID- 27699009
TI  - Alcohol consumption and risk of subarachnoid hemorrhage: A meta-analysis of 14
      observational studies.
AB  - The association between alcohol consumption and the risk of subarachnoid
      hemorrhage (SAH) is inconsistent. Thus, meta- and a dose-response analyses are
      presented with the purpose of assessing their associations. A systematic
      literature search was performed using Pubmed and Embase electronic databases for
      pertinent observational studies. Random-effects or fixed-effect models were
      employed to combine the estimates of the relative risks (RRs) with corresponding
      95% confidence intervals (CIs). A dose-response pattern was conducted for further
      analysis. The current meta-analysis includes 14 observational studies reporting
      data on 483,553 individuals and 2,556 patients. The combined RRs of light alcohol
      consumption (<15 g/day) and moderate alcohol consumption (15-30 g/day) compared
      with teetotal individuals were 1.27 (95% CI: 0.95, 1.68) and 1.33 (95% CI: 0.84,
      2.09), respectively, which indicated no significant association between light-to
      moderate alcohol consumption and SAH. An increased risk of SAH was noted in heavy
      alcohol consumption (>30 g/day) when compared with no alcohol consumption, as
      demonstrated by a result of 1.78 (95% CI: 1.46, 2.17). Dose-response analysis
      showed evidence of a linear association (P=0.0125) between alcohol consumption
      and SAH. The risk of SAH increased by 12.1% when alcohol consumption was
      increased by 10 g/day. Therefore, heavy alcohol consumption was found to be
      associated with an increased risk of SAH. Furthermore, the association between
      SAH and alcohol consumption has clinical relevance with regard to risk factor
      modification and the primary and secondary prevention of SAH.

PMID- 27699010
TI  - Changes in c-Kit expression levels during the course of radiation therapy for
      nasopharyngeal carcinoma.
AB  - In the era of intensity-modulated radiotherapy, distant metastasis is currently
      the main cause of treatment failure for nasopharyngeal carcinoma (NPC).
      Additional therapeutic strategies are required to control the metastasis and
      improve survival. One strategy is targeted therapy, for example against c-Kit. In
      the current study, the frequency of c-Kit expression was determined
      immunohistochemically in 106 NPC patients. c-Kit expression changes during the
      course of radiation therapy were detected in 41 cases via weekly biopsy. Twelve
      cases (11.3%) had c-Kit expression scores of 3+ and 16 (15.1%) had scores of 2+.
      Thus, c-Kit overexpression (2+ or 3+) was observed in 28 (26.4%) patients. There
      were 35 (33.0%) and 43 (40.6%) patients with c-Kit expression scores of 1+ and 0,
      respectively. Furthermore, a trend of decreased c-Kit expression was observed
      after commencing radiotherapy according to the 41 NPC patients who were biopsied
      weekly. Therefore, c-Kit overexpression was identified to be common in NPC, and
      evaluating c-Kit as a therapeutic target for metastatic NPC via c-Kit
      overexpression subsequent to first line treatment may be of interest. To the best
      of our knowledge, the present study is the first to demonstrate a trend of
      decreased c-Kit expression during the course of radiotherapy.

PMID- 27699011
TI  - Effect of L-thyroxine treatment versus a placebo on serum lipid levels in
      patients with sub-clinical hypothyroidism.
AB  - Sub-clinical hypothyroidism is a common disease and whether L-thyroxine
      replacement treatment improves serum lipid levels in affected patients remains
      controversial. Thus, the aim of the present meta-analysis was to assess the
      effect of L-thyroxine therapy on serum lipid levels in sub-clinical
      hyperthyroidism. Relevant randomized controlled trials (RCTs) containing
      continuous data, published until July 2015 were retrieved from the Cochrane
      Library, PubMed, Medline, Google Scholar and Embase databases and subjected to
      meta-analysis using Review Manager software version 5.2 (The Nordic Cochrane
      Centre, Copenhagen, Denmark). Seven RCTs comprising 319 patients were included.
      The overall methodological quality of the RCTs was good. Statistical analysis
      revealed that serum low-density lipoprotein-cholesterol (LDL-C) levels were
      significantly decreased after L-thyroxine treatment [mean difference (MD): -0.23;
      95% confidence interval: -0.44, -0.03; P=0.02], while changes of total
      cholesterol (TC), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL
      C) were not significant (MD: -0.18, P=0.09; MD: -0.02, P=0.78; and MD: -0.06,
      P=0.14, respectively). In conclusion, the meta-analysis performed in the present
      study revealed that compared with placebo treatment, L-thyroxine significantly
      improved serum LDL-C levels in patients with sub-clinical hypothyroidism, while
      not significantly affecting TC, TG and HDL-C levels.

PMID- 27699012
TI  - Lipopolysaccharide-binding protein is efficient in biodosimetry during
      radiotherapy of lung cancer.
AB  - The aim of the present study was to determine if the serum levels of early
      markers of inflammation, such as interleukin-6 (IL-6), tumor necrosis factor
      alpha (TNF-alpha), C-reactive protein (CRP), and lipopolysaccharide-binding
      protein (LBP) were correlated with the radiation dose received by the pulmonary
      and mediastinal structures of patients with non-small cell lung cancer (NSCLC).
      This pilot study included 26 patients with NSCLC who received total radiation
      doses ranging from 54 to 74 Gy (2.0 Gy/fraction). Cytokines were measured at
      baseline by enzyme-linked immunosorbant assay, and following administration of
      total doses of 20 and 40 Gy. A control group of 26 participants was sampled for
      comparisons with patient baseline cytokine levels. Only data from the 40-Gy
      cytokine blood levels of patients with NSCLC were identified to be correlated
      with histograms of the parameters of each patient's radiotherapy protocol. The IL
      6, TNF-alpha and CRP median baseline levels of the patients with NSCLC were
      significantly higher than those of the controls (all P<=0.01). No differences
      were observed between the LBP levels of the patients and controls [median, 36.34
      (25-75%; 31.35-39.27) vs. 36.92 (30.20-44.05) ug/ml, respectively; P=0.42]. No
      significant differences in the levels of the four cytokines between baseline, and
      at 20 and 40 Gy were observed [IL-6 (P=0.19); TNF-alpha (P=0.68); CRP (P=0.44)
      and LBP (P=0.29)]. LBP was significantly and positively correlated with the mean
      radiation dose to the lung (r=0.409; P=0.038), and showed a positive correlation
      with the percentage of lung volume exposed to at least 20 Gy of the planned
      radiation dose (r=0.3536; P=0.0764). CRP levels were positively correlated with
      the mean radiation dose to the esophagus (r=0.404; P=0.041); however, IL-6, TNF
      alpha and CRP were not significantly associated with other lung dosimetry
      parameters. Thus, LBP levels were correlated with radiation exposure of pulmonary
      tissues, and LBP may be a marker that warrants further investigation on
      radiotoxicity in NSCLC patients.

PMID- 27699013
TI  - FEN1 -69G>A and +4150G>T polymorphisms and breast cancer risk.
AB  - Flap endonuclease 1 (FEN1), a DNA repair protein, is important in preventing
      carcinogenesis. Two functional germ line variants -69G>A (rs174538) and +4150G>T
      (rs4246215) in the FEN1 gene have been associated with risk of various types of
      cancer. The aim of the present study was to evaluate the possible impact of FEN1
      polymorphisms on risk of breast cancer (BC) in a sample of Iranian subjects. The
      FEN1 -69G>A and +4150G>T polymorphisms were analyzed in a case-control study that
      included 266 BC patients and 225 healthy females. Polymerase chain reaction
      restriction fragment length polymorphism analysis was used to genotype the
      variants. The findings demonstrated that the FEN1 -69G>A and +4150G>T
      polymorphisms were not associated with BC risk in co-dominant, dominant and
      recessive inheritance models. The findings indicated that GG/GT, GA/GG and GA/TT
      genotypes significantly decreased the risk of BC when compared with 
      69GG/+4150GG. Furthermore, haplotype analysis indicated that -69G/+4150T as well
      as -69A/+4150G significantly decreased the risk of BC compared with -69G/+4150G.
      Thus, these findings demonstrated that haplotypes of FEN1 -69G>A and +4150G>T
      polymorphisms decreased the risk of BC in an Iranian population. Further studies
      with larger sample sizes and different ethnicities are required to validate the
      present findings.

PMID- 27699014
TI  - Analysis of the add-on effect of alpha-glucosidase inhibitor, acarbose in insulin
      therapy: A pilot study.
AB  - The aim of the present study was to evaluate the add-on effect of acarbose
      therapy in oxidative stress, and the lipid and inflammatory profiles of patients
      with type 2 diabetes mellitus (T2DM) treated with insulin. This was an open and
      unblended study. Patients (n=134) with T2DM (haemoglobin A1c range, 9.0-12.0%)
      were recruited. After continuous subcutaneous insulin infusion for 7 days for
      initial rapid correction of hyperglycaemia, a premixed insulin titration period
      (duration, 4-6 days) subsequently followed. Patients were then randomized (1:1)
      into two groups as follows: An acarbose plus pre-mixed 30/70 insulin group or a
      pre-mixed 30/70 insulin only group; each group received treatment for 2 weeks.
      Plasma high-sensitivity C-reactive protein (Hs-CRP), 8-iso-prostaglandin F2alpha
      (8-iso PGF2alpha), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)
      1beta, and IL-6 levels were measured before and after therapy. Patients that
      received acarbose plus insulin demonstrated greater reduction in 8-iso PGF2alpha,
      Hs-CRP, TNF-alpha, IL-1beta and IL-6 levels when compared with the insulin only
      patients. Thus, acarbose add-on insulin therapy was identified to be associated
      with greater improvements in oxidative stress and inflammation in patients with
      T2DM when compared with those that received insulin only therapy.

PMID- 27699015
TI  - Association of DNA methyltransferase polymorphisms with susceptibility to primary
      gouty arthritis.
AB  - Gouty arthritis is the most common type of inflammatory and immune disease, and
      the prevalence and incidence of gout increases annually. Genetic variations in
      the DNA methyltransferases (DNMTs) gene have not, to the best of our knowledge,
      been reported to influence gene expression and to participate in the pathogenesis
      of gout. The aim of the present study was to investigate whether the DNMT1,
      DNMT3A and DNMT3B polymorphisms contribute to gout susceptibility. These
      polymorphisms were screened for in 336 gout patients and 306 healthy control
      subjects (from a South China population) for association with gout. The
      distribution frequencies of DNMT1 rs2228611 AA genotype (P=0.007) and A allele
      (P=0.002; odds ratio=1.508, 95% confidence interval=1.158-1.964) were found to be
      significantly increased in the gout patients when compared with those in the
      healthy control subjects. The rs1550117 in DNMT3A and rs2424913 in DNMT3B
      exhibited no significant associations with gout susceptibility between the
      patients and control subjects. These results demonstrated that the DNMT1
      rs2228611 polymorphism may be involved in the pathogenesis of gout, while DNMT3A
      rs1550117 and DNMT3B rs2424913 did not show any obvious significance in the
      current study; thus, may not be used as risk factors to predict the
      susceptibility to gout. However, further studies are required to investigate the
      functions and regulatory mechanism of the polymorphisms of DNMTs in gout.

PMID- 27699016
TI  - Resistin-induced cardiomyocyte hypertrophy is inhibited by apelin through the
      inactivation of extracellular signal-regulated kinase signaling pathway in H9c2
      embryonic rat cardiomyocytes.
AB  - It has been reported that resistin induces, whereas apelin inhibits cardiac
      hypertrophy. However, the underlying molecular mechanisms of apelin inhibiting
      resistin-induced cardiac hypertrophy remain unclear. The aim of the current study
      is to investigate the effects of apelin on resistin-induced cardiomyocyte
      hypertrophy and elucidate the underlying molecular mechanism. H9c2 cells were
      used in the present study, and cell surface area and protein synthesis were
      evaluated. Reverse transcription-quantitative polymerase chain reaction was
      performed to analyze the expression levels of hypertrophic markers, brain
      natriuretic peptide (BNP) and beta-myosin heavy chain (beta-MHC). In addition,
      western blotting was conducted to examine phosphorylation of extracellular signal
      regulated kinase (ERK)1/2. Following treatment of H9c2 cells with resistin, cell
      surface area, protein synthesis, and BNP and beta-MHC mRNA expression levels were
      increased. Subsequent to co-treatment of H9c2 cells with apelin and resistin,
      lead to the inhibition of resistin-induced hypertrophic effects by apelin. In
      addition, treatment with resistin increased phosphorylation of ERK1/2, whereas
      pretreatment with apelin decreased phosphorylation of ERK1/2, which was increased
      by resistin. These results indicate that resistin-induced cardiac hypertrophy is
      inhibited by apelin via inactivation of ERK1/2 cell signaling.

PMID- 27699017
TI  - Change ratio of hemoglobin has predictive value for upper gastrointestinal
      bleeding.
AB  - The present study aimed to identify novel predictors of upper gastrointestinal
      (GI) bleeding by assessing change ratios of blood test variables. Records of
      1,023 patients (431 men and 592 women) who underwent endoscopy between October
      2014 and September 2015 at the National Hospital Organization Shimoshizu Hospital
      (Yotsukaido, Japan) were retrospectively analyzed. Patients whose blood test
      variables for the time-point of endoscopy and three months previously were
      available were enrolled and subsequently categorized into a group with and
      another one without upper GI bleeding (n=32 and 84, respectively), and the
      respective change ratios were calculated for each group. One-way analysis of
      variance revealed that in patients with upper GI bleeding, change ratios of white
      blood cell count and alkaline phosphatase were significantly higher than those in
      patients without, while change ratios of hemoglobin (Hb), total protein and
      albumin were significantly reduced. Logistic regression analysis demonstrated
      that the change ratio of Hb was significantly correlated with upper GI bleeding.
      Receiver-operator characteristic analysis revealed that an 18.7% reduction of Hb
      was the threshold value for the prediction of upper GI bleeding. In conclusion,
      the present study revealed that a >=18.7% reduction in Hb over three months has
      predictive value for upper GI bleeding.

PMID- 27699018
TI  - Early prophylactic anticoagulation for portal vein system thrombosis after
      splenectomy: A systematic review and meta-analysis.
AB  - A systematic review and meta-analysis were conducted to evaluate the efficacy and
      safety of early prophylactic anticoagulation for the prevention of portal vein
      system thrombosis (PVST) after splenectomy. A systematic search of the PubMed,
      EMBASE, Springer and Cochrane Library databases was performed to identify studies
      comparing the outcomes in patients receiving or not receiving regular
      prophylactic anticoagulation after splenectomy. The quality of the included
      studies was assessed using the Jadad Score and the Newcastle-Ottawa Scale.
      Heterogeneity was evaluated using the chi2 and I2 tests. The parameters that were
      analyzed included the incidence of PVST and anticoagulation-associated
      complications. A total of seven studies qualified for the review, involving 383
      and 283 patients receiving or not receiving regular prophylactic anticoagulation,
      respectively. The incidence of PVST was significantly reduced with an odds ratio
      (OR) of 0.31 [95% confidence interval (CI), 0.21-0.46; P<0.00001] in the regular
      prophylactic anticoagulation group compared with the control group. No difference
      in the incidence of anticoagulation-associated complications was identified
      between the two groups (OR=0.60, 95% CI, 0.23-1.56; P=0.30). Early prophylactic
      anticoagulation was associated with a reduced incidence of PVST, although it was
      not associated with the incidence of anticoagulation-associated complications.
      These results indicate that prophylactic anticoagulation could be safely
      administered after splenectomy, even to cirrhotic patients.

PMID- 27699019
TI  - Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric
      arteries.
AB  - Independent of its lipid-lowering properties, simvastatin (Sim) induces
      vasorelaxation; however, the underlying mechanisms have remained elusive. The aim
      of the present study was to investigate the vasorelaxant effects of Sim on rat
      superior mesenteric arteries and the mechanisms involved. The isometric tension
      of rat superior mesenteric arterial rings was recorded in vitro on a myograph.
      The results showed that Sim concentration-dependently relaxed the superior
      mesenteric artery rings with endothelium pre-contracted by phenylephrine
      hydrochloride [maximum relaxation (Emax)=51.05+/-4.09%; negative logarithm of the
      concentration that caused 50% of the maximum response (pD2)=4.17+/-0.18] or KCl
      (Emax=41.65+/-1.32%; pD2=3.55+/-0.1). Nomega-nitro-L-arginine methyl ester (100
      uM) significantly inhibited this effect, while it was not affected by 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 uM) and indomethacin (5 uM). In
      artery rings without endothelium, vasorelaxation induced by Sim was attenuated by
      4-aminopyridine (100 uM), but was not affected by barium chloride dehydrate (10
      uM), glibenclamide (10 uM) and traethylammonium chloride (1 mM). Moreover, Sim
      also inhibited the contraction induced by increasing external calcium in Ca2+
      free medium with added KCl (60 mM). These results suggested that Sim induces
      relaxation of superior mesenteric arterial rings through an endothelium-dependent
      pathway, involving nitric oxide release and also through an endothelium
      independent pathway, involving the opening of voltage-dependent K+ channels and
      blockade of extracellular Ca2+ influx.

PMID- 27699020
TI  - Efficacy of daiokanzoto in chronic constipation refractory to first-line
      laxatives.
AB  - There are only a few treatment options for constipation and limited evidence of
      suitable treatments. Daiokanzoto (DKT) is a Kampo medicine often used clincally
      to treat constipation. DKT is a laxative used predominantly in Japan; however,
      clinical data on its efficacy and safety is lacking. Patients who used DKT, but
      were intolerant to either magnesium oxide (MgO; MgO group; n=16) or senna extract
      (Senna group; n=26) were included in the present study. The frequencies of their
      bowel movements were compared during the 1 week prior to and following DKT
      administration. Within 24 hours after DKT administration, 93.8% of the patients
      in the MgO group evacuated their bowels. The median bowel movement frequency 1
      week prior to DKT administration was 2.5 and 1 week after DKT administration was
      significantly increased to 7.5. In the Senna group, within 24 h of DKT
      administration, 80.8% of the patients evacuated their bowels. The median bowel
      movement frequency 1 week prior to the DKT treatment was 2.0, which significantly
      increased to 8.5 1 week after the administration of DKT. The adverse events from
      DKT treatment were mild and controllable.

PMID- 27699021
TI  - A model for predicting nosocomial carbapenem-resistant Klebsiella pneumoniae
      infection.
AB  - Mortality associated with infections due to carbapenem-resistant Klebsiella
      pneumoniae (CR-KP) is high and the infections need to be predicted early. The
      risk factors for CR-KP infection are heterogeneous. The aim of the present study
      was to construct a model allowing for the early prediction of CR-KP infection.
      Nosocomial infections due to K. pneumoniae were evaluated retrospectively over a
      2-year period. The case cohort consisted of 370 inpatients with CR-KP infection.
      For each case enrolled, two matched controls with no CR-KP infection during their
      hospitalization were randomly selected. Matching involved month of admission,
      ward, as well as interval days. The Vitek 2 system was used for identification of
      isolates and antimicrobial susceptibility testing. General linear model with
      logistic regression was used to identify possible risk factors. The predicted
      power of the model was expressed as the area under the receiver-operating
      characteristic curve. Age, male gender, with cardiovascular disease, hospital
      stay, recent admission to intensive care unit, indwelling urinary catheter,
      mechanical ventilation, recent beta-lactam-beta-lactamase inhibitors, fourth
      generation cephalosporins and/or carbapenems therapy were independent risk
      factors for CR-KP infection. Models predicting CR-KP infection developed by
      cumulative risk factors exhibited good power, with areas under the receiver
      operating characteristic curves of 0.902 [95% confidence interval (CI), 0.883
      0.920; P<0.001] and 0.899 (95% CI, 0.877-0.921; P<0.001) after filtering by age
      (>=70 years). The Yonden index was at the maximum when the cumulative risk
      factors were >=3 in the two prediction models. The results show that the
      prediction model developed in the present study might be useful for controlling
      infections caused by CR-KP strains.

PMID- 27699022
TI  - Transcription factor 4 gene rs9960767 polymorphism in bipolar disorder.
AB  - The transcription factor 4 (TCF4) gene encodes a helix-loop-helix transcription
      factor protein, which initiates neuronal differentiation and is primarily
      expressed during nervous system development. The aim of the present study is to
      investigate the association of the TCF4 rs9960767 polymorphism and bipolar
      disorder, which is highly heritable. DNA isolation was performed on 95 patients
      with bipolar disorder and 108 healthy control subjects to examine the TCF4
      rs9960767 polymorphism. Genotypic and allelic frequencies were determined using
      the polymerase chain reaction-restriction fragment length polymorphism method
      designed in our laboratory. Statistical analysis was performed using chi2 test
      within the 95% confidence interval. Odds ratios were calculated and Hardy
      Weinberg equilibrium (HWE) was verified for all control subjects and patients.
      The A allele frequency was 95.8% in the patients and 94.4% in the control
      subjects, and 4.2% in the patients and 5.6% in the control subjects for the C
      allele. The genotype frequencies of the TCF4 gene rs9960767 variant were as
      follows: AA, 91.6% and AC, 8.4% in patients with bipolar (CC genotype was not
      observed in cases); AA, 89.8%; AC, 9.3% and CC, 0.9% in the control subjects. No
      statistically significant difference was identified between the patients and
      control subjects (chi2=0.937; P=0.626). In addition, gender specific analysis was
      performed, although no significant association was found according to the gender
      distrubition. All patients and control subjects were in HWE (P>0.05). Statistical
      analysis of the data indicates that the TCF4 gene rs9960767 polymorphism is not
      an independent risk factor for bipolar disorder in the overall population or in
      terms of gender; however, an increased population size would improve the
      statistical power. Furthermore, additional gene variants that are specifically
      involved in neuronal development may be analyzed for revealing the complex
      genetic architecture of bipolar disorder. An improved approach would be better to
      evaluate the TCF4 gene in a pathway specific manner due to its role as a
      transcription factor.

PMID- 27699023
TI  - Elevated serum levels of two anti-neutrophil cytoplasmic antibodies in a lung
      cancer patient: A case report.
AB  - A 71-year-old woman with arthralgia and lung fibrosis was referred to Mito Kyodo
      General Hospital (Mito, Japan) for a mass, which was incidentally observed on a
      chest radiograph. The chest computed tomography scan demonstrated fibrotic
      lesions in the lower lobes of the lung and a nodule in the left upper lobe. The
      serum levels of myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)
      and proteinase 3 (PR3)-ANCA were 60.3 and 7.5 U/ml, respectively. A
      transbronchial biopsy obtained from the nodule in the left upper lobe of the lung
      revealed a lung adenocarcinoma and the patient underwent standard upper lobectomy
      of the left lung. Subsequent to the resection, the serum levels of PR3-ANCA and
      MPO-ANCA returned to 10.0 and <1.0 U/ml, respectively. Notably, titers of
      antinuclear antibodies were also decreased during the postoperative course.
      Although elevated serum ANCA levels are rarely seen in lung cancer, they may be
      associated with the occurrence of lung cancer in certain patients, as observed in
      the present case.

PMID- 27699024
TI  - Intratumoral hemorrhage-related differences in the expression of vascular
      endothelial growth factor, basic fibroblast growth factor and thioredoxin
      reductase 1 in human glioblastoma.
AB  - The present study was designed to evaluate the expression of vascular endothelial
      growth factor (VEGF), basic fibroblast growth factor (bFGF) and thioredoxin
      reductase 1 (TrxR1) in glioblastoma multiforme (GBM) with and without
      intratumoral hemorrhage. Surgically resected human GBM samples from 20 patients
      who underwent surgery at our institute were extracted from the histopathological
      specimens and divided into two groups. A total of 10 samples from each type of
      GBM (World Health Organization grade IV, intratumoral hemorrhage-positive or 
      negative) were included in each group. VEGF, bFGF and TrxR1 expression was
      analyzed using immunohistochemistry and the results were compared between groups.
      VEGF and bFGF immunoreactivity was significantly higher in GBMs containing
      intratumoral hemorrhage. Furthermore, VEGF, bFGF and TrxR1 immunointensity was
      significantly higher in GBMs containing intratumoral hemorrhage. Thus, the
      present study demonstrated a higher VEGF, bFGF and TrxR1 expression in GBMs
      contain intratumoral hemorrhage, indicatiogn a role of VEGF, bFGF and TrxR1
      expression in the promotion of tumoral angiogenesis and tumoral growth by complex
      mechanisms that require further elucidation.

PMID- 27699025
TI  - Allogeneic stem cell transplantation in a blast-phase chronic myeloid leukemia
      patient with carbapenem-resistant Klebsiella pneumoniae tricuspid valve
      endocarditis: A case report.
AB  - In chronic myeloid leukemia (CML), the occurrence of blastic transformation is
      rare. Treatment outcome is generally poor. Allogeneic stem cell transplantation
      (allo-SCT) is the only potentially curative treatment option for advanced-phase
      CML. Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP)
      isolates are associated with high morbidity and mortality rates, particularly in
      patients with haematological malignancies. Infection and colonization by these
      multiresistant bacteria may represent a challenge in SCT recipients for the
      management of post-transplantation complications, as well as for the eligibility
      to receive a transplant in patients who acquire the pathogen prior to the
      procedure. We herein report the case of a blast-phase CML patient with a highly
      resistant, CRKP-associated tricuspid valve endocarditis, who was treated with a
      combination of systemic antimicrobial therapy and surgical valve repair, and
      subsequently underwent a successful allo-SCT.

PMID- 27699026
TI  - Clinical and imaging characteristics of 53 ulcers of post-radiation
      nasopharyngeal necrosis in patients with nasopharyngeal carcinoma.
AB  - It is widely accepted that a mucosal ulcer induced by radiation (RIMU) is the
      predominant type of post-radiation nasopharyngeal ulcer in patients with
      nasopharyngeal carcinoma (NPC) who underwent radiotherapy (RT); however, another
      type of ulcer, an ulcer of post-radiation nasopharyngeal necrosis (UPRNN), has
      rarely been reported for patients with NPC. In the present study, the clinical
      and imaging features of 53 patients who were treated at the Zhejiang Provincial
      Cancer Center (Zhejiang Cancer Hospital, Hangzhou, China) between March 2009 and
      December 2015, and who were diagnosed with UPRNN, were reviewed. The clinical
      factors, laboratory examinations, magnetic resonance imaging (MRI) features and
      endoscopic findings were analysed. A UPRNN has its characteristic imaging
      features and ulcer locations at the primary tumour bed, which are different from
      a traditional RIMU. In the retrospective analysis of the clinical factors, a
      tumour (T) 3/4 stage, with invasion of muscular tissue, poor response of
      neoadjuvant chemotherapy and anaemia during the RT, may be associated with the
      occurrence of a UPRNN. To evaluate the severity, a UPRNN was divided into three
      grades according to the invasion depth of the ulcer based on its appearance in
      MRI, and the subsequent treatment and prognosis varied according to the severity
      of the UPRNN. In conclusion, a UPRNN has its clinical features and characteristic
      MRI appearances, and the occurrence of a UPRNN may be associated with several
      clinical factors.

PMID- 27699027
TI  - Replacement of the tumor bed following oncoplastic breast-conserving surgery with
      immediate latissimus dorsi mini-flap.
AB  - The aim of the present study was to evaluate the geographic variability of the
      tumor bed following oncoplastic breast-conserving surgery (OP-BCS), and to assess
      its relevance for radiotherapy planning. In this prospective study, pre- and
      postoperative computerized tomography (CT) scans of 22 patients with early-stage
      breast cancer were fused. The preoperative gross tumor volume or excisional
      biopsy cavity were contoured under the guidance of preoperative radiological
      images. Postoperative lumpectomy cavities were contoured under the guidance of
      surgical clips. The conformity index (CI) was calculated and defined on a scale
      between 0 and 1, where 0 indicated no overlap and 1 indicated 100% concordance.
      Associations between CI and the number of clips, time interval between surgery
      and CT scans, pathological tumor size and age were assessed using independent
      sample testing. The median CI was 0.07 (in five cases, 1, and in eight cases, 0).
      The lumpectomy cavity shifted from the primary location in 36.4% of the cases.
      Median shifts between the isocenters of pre- and postoperative volumes were
      measured as 1.02 cm (range, 0.4-4.43 cm) in the x, 1.07 cm (range, 0.05-5.67 cm)
      in the y, and 1.12 cm (range, 0-3.75 cm) in the z directions. Only the clip
      number was determined to be significantly associated with CI (P=0.017). Pre- and
      postoperative tumor bed volumes were fully superposed in five of the 22 cases.
      The present study has shown that the tumor bed is markedly replaced following OP
      BCS with latissimus dorsi mini-flap (LDMF) reconstruction. Special care should
      therefore be taken when defining the lumpectomy cavity following OP-BCS with LDMF
      reconstruction.

PMID- 27699028
TI  - Expression of the glucocorticoid receptor in breast cancer-associated
      fibroblasts.
AB  - Cancer- associated fibroblasts (CAFs) are actively involved in breast carcinoma.
      Our previous study demonstrated that the majority of these CAFs were smooth
      muscle actin (SMA) positive and were therefore termed peritumoral myofibroblast
      (PMY). Glucocorticoid, linked or not with its receptor (GR), has been postulated
      to serve a major role in normal breast and breast carcinoma; however, their role
      in CAFs remains poorly understood. The aim of the present study was to assess the
      presence of GR in breast CAFs and particularly in PMY in 56 cases of invasive
      breast carcinoma in correlation with clinicopathological parameters, by
      immunohistochemistry. GR was observed in CAFs in 51 cases (91%) and were more
      frequent in luminal A subtype (19/19 cases; 100%). The stromal expression was
      statistically correlated with the tumor grade (P=0.03), the Ki-67 index (P=0.003)
      and the presence of GR in the epithelial component (P=0.01). The demonstration of
      a frequent expression of GR in breast CAFs may serve as an interesting target for
      future therapeutics for the regulation of the tumoral breast microenvironment.

PMID- 27699029
TI  - Polaprezinc protects normal intestinal epithelium against exposure to ionizing
      radiation in mice.
AB  - Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant
      effects. The purpose of the present study was to assess the radioprotective
      effects of PZ in the normal intestine of C57BL/6J mice. PZ was orally
      administered at 100 mg/kg body weight in the drinking water. Firstly, the present
      study compared the survival of normal intestinal crypt epithelial cells with mice
      that received PZ prior to or following irradiation. Next, the present study
      examined the sequential changes of the incidence of apoptosis in the normal
      intestine of mice that received irradiation. The mice that received PZ prior to
      irradiation demonstrated a stronger protective effect on the normal intestine
      compared with those that received PZ after irradiation. The present study
      therefore administrated PZ 2 h before irradiation in the subsequent experiments.
      The mice receiving PZ developed fewer apoptotic cells in the duodenum, jejunum
      and ileum. Radiation-induced cell death occurred with a peak at position 10 or
      lower from the base of the crypt axis, and was subsequently reduced by PZ
      treatment. Pretreatment with PZ protected the normal intestinal tissues from
      radiation-induced apoptosis.

PMID- 27699030
TI  - Chemotherapy-induced fatal hepatitis B virus reactivation in a small-cell lung
      cancer patient.
AB  - Hepatitis B virus (HBV) reactivation during chemotherapy is a major concern and
      is widely reported, particularly in association with hematological malignancies
      and lymphomas. While lung cancer ranks first in incidence and mortality
      worldwide, HBV reactivation has been largely overlooked in this disease. As
      regards small-cell lung cancer (SCLC), HBV reactivation has rarely been reported.
      We herein report the case of a hepatitis B surface antigen-seropositive SCLC
      patient in whom HBV was reactivated during the course of chemotherapy, despite
      preemptive use of lamivudine. The patient developed fulminant viral hepatitis and
      succumbed to liver failure. The aim of this report was to highlight the major but
      overlooked issue of HBV reactivation in SCLC, and suggest that agents more potent
      than lamivudine may be more efficacious in high-risk patients.

PMID- 27699031
TI  - Outpatient management without initial assessment for febrile patients undergoing
      adjuvant chemotherapy for breast cancer.
AB  - The purpose of this study was to retrospectively analyze the feasibility of
      outpatient management without initial assessment for febrile patients undergoing
      adjuvant chemotherapy for breast cancer. A total of 131 consecutive patients with
      breast cancer treated with adjuvant or neoadjuvant chemotherapy from 2011 to 2013
      at Osaka Medical College Hospital (Osaka, Japan) were retrospectively reviewed.
      In the case of developing a fever (body temperature, >=38 degrees C), the
      outpatients had been instructed to take previously prescribed oral antibiotics
      for 3 days without any initial assessment, and if no improvement had occurred by
      then, they were required to visit the hospital for examination and to undergo
      treatment based on the results of a risk assessment for complications. The
      primary aim of the present study was to assess the outcome of febrile episodes,
      while the secondary aim was to assess the incidence of febrile episodes,
      hospitalizations, and the type of chemotherapy. The 131 patients received 840
      chemotherapy administrations. Fifty-five patients (42.0%) had a total of 75
      febrile episodes after 840 chemotherapy administrations (8.9%). Treatment failure
      occurred in 12 of the 75 episodes (16.0%) in 11 of the 55 patients (20.0%). Only
      four episodes required hospitalization. Treatment success was achieved in 63
      episodes (84.0%). In conclusion, the feasibility of outpatient management without
      initial assessment was evaluated in the present study for febrile patients
      undergoing adjuvant chemotherapy for breast cancer, and the outpatient strategy
      regimen may be safe and convenient for these patients.

PMID- 27699032
TI  - Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced
      recurrent colorectal cancer.
AB  - The aim of this study was to evaluate the efficacy and safety of co
      administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab
      (bev) in patients with advanced recurrent colorectal cancer. A retrospective
      study of 36 patients with advanced recurrent colorectal cancer was performed, of
      whom 27 received first-line and 9 received second-line SOX+bev chemotherapy
      between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji,
      Japan). The SOX+bev regimen consisted of administration of intravenous
      oxaliplatin (85 mg/m2) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co
      administration of oral S-1 twice daily on days 1-14. The drug regimen was
      repeated every 4 weeks. SOX+bev treatment was associated with a response rate of
      45.2%, a disease control rate of 71%, and a median progression-free survival
      (PFS) and overall survival (OS) of 9.9 and 21.9 months, respectively. Patients
      who received first-line chemotherapy benefited from treatment in terms of
      prolonged PFS (13.8 months) and OS (28.2 months). Grade 3/4 adverse events were
      infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory
      neuropathy, increased aspartate aminotransferase level and skin rash. In
      conclusion, SOX+bev therapy was found to be feasible and safe for patients with
      advanced and recurrent colorectal cancer.

PMID- 27699033
TI  - Effect of ARID1A/BAF250a expression on carcinogenesis and clinicopathological
      factors in pure-type clear cell adenocarcinoma of the ovary.
AB  - Frequent mutation of the ARID1A gene has been recently identified in ovarian
      clear-cell adenocarcinoma (CCA); however, the clinical significance of BAF250a
      expression encoded by the ARID1A gene remains to be determined. The aim of the
      present study was to assess whether BAF250a expression had an impact on the
      clinical features of CCA. A total of 97 cases of CCA treated at a single
      institution were enrolled in the present study. The tissue samples were evaluated
      by immunohistochemical staining. BAF250a-deficient expression was observed in 30%
      (29/97) of all CCA cases. Of this, 19% of non-atypical endometriosis, 26% of
      atypical endometriosis, 39% of endometriosis-related CCA, 5% of benign clear-cell
      adenofibroma (CCAF), 5% of borderline CCAF and 10% of CCAF-related CCA. BAF250a
      deficient expression was significantly more frequent in endometriosis-related CCA
      compared with that in CCAF-related CCA (P=0.02). No significant difference was
      observed in the response rate of primary chemotherapy according to BAF250a
      expression status (P=0.48). Additionally, BAF250a expression status was not
      significantly correlated with progression-free and overall survival in patients
      with CCA. Although loss of BAF250a expression was associated with early
      tumorigenesis in endometriosis-related CCA, this alteration was not significantly
      correlated with chemosensitivity and prognoses of CCA. Further biomarker
      analyses, including BAF250a expression, are required to improve the prognoses of
      CCA.

PMID- 27699034
TI  - Analysis of blood neutrophil elastase, glutathione levels and pathological
      findings in postoperative acute exacerbation of idiopathic pulmonary fibrosis
      associated with lung cancer: Two case reports.
AB  - Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is characterized
      by severe worsening dyspnea and high mortality. It has been proven that the serum
      neutrophil elastase (NE) level, in addition to the serum Krebs von den Lungen-6
      (KL-6) and surfactant protein-D (SP-D) levels, was elevated in patients with IPF
      AE. Glutathione (GSH) is the major antioxidant involved in cell metabolism and
      survival. It is also known that IPF is characterized by reduced GSH levels in
      bronchoalveolar lavage fluid and blood. Case 1 was a 67-year-old man who was
      referred to our hospital complaining of a 2-year history of progressive dyspnea
      on exertion (DOE). The patient was initially diagnosed with IPF, followed by
      inhaled N-acetylcysteine monotherapy. Two years later, left upper lobectomy with
      lymph node dissection was performed due to primary lung cancer, which was large
      cell neuroendocrine carcinoma (pT2aN2M0, stage IIIA). Five days after lung
      surgery, the patient developed AE. Case 2 was a 67-year-old man who was referred
      to our hospital with suspected lung cancer, complaining of dry cough and DOE. The
      patient underwent left upper lobectomy with lymph node dissection for primary
      lung cancer, which was diagnosed as well-differentiated adenocarcinoma (pT2aN2M0,
      stage IIIA). Ten days after lung surgery, the patient developed AE. The levels of
      biomarkers, such as serum NE, redox balance [reduced GSH (rGSH)/oxidized GSH
      (GSSG)] in the blood, as well as the correlation between serial changes of these
      biomarkers and prognosis, were analyzed in 2 patients with postoperative IPF-AE
      associated with lung cancer. Interestingly, the serial changes of the serum
      rGSH/GSSG ratio may suggest the possibility of predicting the onset of
      postoperative AE and/or survival, along with serum NE levels.

PMID- 27699035
TI  - Membranous nephropathy associated with malignant pleural mesothelioma in an adult
      patient: A case report.
AB  - A 23-year-old man presented to our hospital with membranous nephropathy and
      received a detailed examination, including pleural biopsy, due to a feeling of
      chest oppression. The result of the pleural biopsy was malignant pleural
      mesothelioma. However, the patient did not have a history of asbestos or tobacco
      exposure. A review of the English literature identified only 7 reported cases of
      concomitant malignant mesothelioma and nephrotic syndrome. Furthermore, among the
      7 cases reviewed, 6 had a history of asbestos exposure, 1 had a history of
      prolonged tobacco exposure and in only 1 case the renal pathology results
      revealed the presence of membranous nephropathy.

PMID- 27699036
TI  - Neoadjuvant chemotherapy followed by conization to spare fertility in cases of
      locally advanced cervical cancer: A case report and review of the literature.
AB  - The average age when cervical cancer is diagnosed is decreasing, resulting in a
      larger proportion of patients seeking fertility preservation. Therefore, a less
      radical approach that aims to preserve the potential for fertility during the
      treatment of cervical carcinoma is crucial. The present study reported a case of
      a patient with stage IB2 cervical cancer who exhibited pathological complete
      regression to neoadjuvant chemotherapy (NACT). This patient underwent deep
      cervical conization and laparoscopic lymphadenectomy to preserve her fertility.
      The patient gave birth at 29 weeks of gestation and exhibited no recurrent
      disease until May 2016 (72 months after surgery). This is the first, to the best
      of our knowledge, IB2 case treatment by NACT, followed by conization plus
      lymphadenectomy, producing favorable oncological and obstetrical outcome. The
      present study, together with data from a limited number of published articles,
      offers a new perspective in the preservation of fertility in young women with
      cervical cancer. Additional studies are required in a selected population.

PMID- 27699037
TI  - Trefoil factor 3 expression in epithelial ovarian cancer exerts a minor effect on
      clinicopathological parameters.
AB  - The role of trefoil factor 3 (intestinal) (TFF3) has been analyzed in numerous
      cancers, such as breast and gastrointestinal cancer, and has been associated with
      poor prognosis. However, the role of TFF3 in ovarian cancers is not clear.
      Expression analysis of TFF3 in 91 ovarian cancer patients was performed by
      immunohistochemistry of primary paraffin-embedded tumor samples. The results were
      scored according to staining intensity and percentage of positive tumor cells
      resulting in an immune-reactive score (IRS) of 0-12. These results were
      correlated with clinicopathological characteristics and survival. TFF3 expression
      in our patient cohort exhibited a tendency towards improved overall and
      progression-free survival (PFS). In TFF3-positive serous and high-grade serous
      ovarian cancers, the median PFS was 27.6 months [95% confidence interval (CI): 0
      55.7] vs. 15.2 months in TFF3-negative tumors (95% CI: 13.8-16.6) (P=0.183). The
      median overall survival was 53.9 months in TFF3-positive tumors (95% CI: Non
      applicable) vs. 44.4 months in TFF3-negative cases (95% CI: 30.5-58.3) (P=0.36).
      TFF3 negativity was significantly associated with higher tumor grade (P=0.05).
      Based on our results, further studies are required in order to elucidate whether
      survival and chemosensitivity are affected by TFF3 expression in ovarian cancer.

PMID- 27699039
TI  - Extracranial oral cavity metastasis from glioblastoma multiforme: A case report.
AB  - Glioblastoma multiforme is the most common primary malignant brain tumor. The
      clinical outcome following diagnosis remains extremely poor. The treatment of
      choice is wide surgical resection of the visible tumor, frequently followed by
      adjuvant combined radiochemotherapy (RCTx) with temozolomide as the
      chemotherapeutic agent. Extracranial metastases are extremely rare, with <200
      cases of extracranial metastases from glioblastoma multiforme reported in the
      literature to date. We herein present a case of a patient suffering from a fast
      growing metastasis to the oral cavity, completely filling the buccal cavity
      within 2 weeks, as the only manifestation of recurrent glioblastoma multiforme
      following initial surgical resection and adjuvant RCTx.

PMID- 27699038
TI  - Improvement of survival with postmastectomy radiotherapy in patients with 1-3
      positive axillary lymph nodes: A systematic review and meta-analysis of the
      current literature.
AB  - In breast cancer with >4 positive axillary lymph nodes, it is common practice to
      deliver radiotherapy to the affected site following mastectomy. However, less is
      known regarding the benefits this may confer on women with 1-3 positive lymph
      nodes. In this meta-analysis, we aimed to assess whether post-mastectomy
      radiotherapy (PMRT) was beneficial for such patients. A literature review was
      conducted using the PubMed and Ovid databases. Selected studies were analysed and
      data regarding overall survival (OS) and locoregional recurrence (LRR) rates were
      extracted. Statistical analysis was then conducted in order to develop a combined
      risk ratio (RR) for both OS and LRR in the setting of PMRT in women with breast
      cancer with 1-3 positive lymph nodes. PMRT in women with 1-3 positive lymph nodes
      significantly reduced the risk of LRR, with a RR of 0.3 [95% confidence interval
      (CI): 0.23-0.38] and also showed a minor benefit in terms of OS (RR=1.03, 95% CI:
      1.00-1.07). Therefore, in breast cancer patients with 1-3 positive lymph nodes,
      PMRT significantly reduced the risk of LRR and was associated with a minor OS
      benefit. Until the results of ongoing randomised controlled trials are published,
      PMRT should be recommended in this group of patients following a careful
      multidisciplinary discussion.

PMID- 27699040
TI  - Distinct patterns of angiogenic factor expression as a predictive factor of
      response to chemotherapy in stage IIIA non-small-cell lung cancer patients.
AB  - The expression of various angiogenic factors was assessed in tumour samples of
      patients with stage III non-small-cell lung cancer (NSCLC) and further evaluated
      in terms of response to induction paclitaxel-ifosfamide-cisplatin chemotherapy.
      Freshly isolated lung tumour specimens obtained by bronchoscopy from 70 stage
      IIIA NSCLC chemotherapy-naive patients were sampled and analysed for vascular
      endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3. Microvessel
      density was assessed through evaluating the angiogenic markers CD34 and CD105.
      Immunostaining scores were calculated by multiplying the percentage of labeled
      cells by the intensity of staining for each examined parameter. The overall mean
      immunostaining score value from all NSCLC samples was 7.83, 5.56 and 15.86 for
      VEGFR-1, VEGFR-2 and VEGFR-3, respectively. The overall mean value of the
      endothelial antigen CD34 was 16.29, whereas the expression of the CD105 antigen
      in endothelial cells yielded a multivariate distribution. Patients who responded
      to chemotherapy expressed significantly higher VEGFR-1 and VEGFR-3 mean values
      compared with non-responders (P<0.001). No significant difference was noted in
      VEGFR-2 mean values between these two groups (P=0.06). The CD34 mean value was
      significantly higher in responders (P<0.001), whereas there was no significant
      difference in CD105 expression between the two groups (P=0.07). Angiogenic marker
      expression proved to be a potential predictive factor of response to chemotherapy
      in stage III NSCLC. which merits further investigation.

PMID- 27699042
TI  - Simultaneous occurrence of non-Hodgkin lymphoma, renal cell carcinoma and
      oncocytoma: A case report.
AB  - We herein report the case of a 74 year-old woman with a diffuse large B-cell
      lymphoma and bilateral renal masses identified on computed tomography scans
      during the initial staging process. Following partial bilateral nephrectomy,
      histopathological examination revealed renal cell carcinoma (RCC) and oncocytoma
      in the left and the right kidneys, respectively. Shortly afterwards, lymphoma of
      the left palatine tonsil was diagnosed and the patient received chemotherapy with
      rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP
      regimen), followed by radiotherapy. Due to metastasis of the RCC to the right
      breast, pancreas and the area of the left psoas major muscle, systemic treatment
      with pazopanib was commenced. To the best of our knowledge, this is the first
      reported case of simultaneous diagnosis of non-Hodgkin lymphoma (NHL), RCC and
      oncocytoma. The aim of this study was to review the related literature, discuss
      issues regarding the management of this unusual case and identify possible common
      etiopathological mechanisms underlying the simultaneous occurrence of NHL, RCC
      and oncocytoma.

PMID- 27699041
TI  - Significance of defect closure following transanal local full-thickness excision
      of rectal malignant tumors.
AB  - Transanal excision (TAE) for rectal tumors is increasingly applied and it is
      generally recommended that the defect following full-thickness excision should be
      closed. The aim of this study was to compare the complications and anal function
      following TAE between cases where the defect was closed and those where it was
      not. A total of 43 consecutive rectal malignant tumor patients eligible for TAE
      were investigated. Regarding anorectal function, incontinence was assessed using
      the Wexner score. The defect of the rectum was closed in 21 of the 43 patients.
      There were no significant differences between the two groups regarding gender,
      distance from the anal verge, tumor size, diagnosis and tumor site. There was a
      significantly higher number of postoperative complications of all grades and
      >=Clavien-Dindo grade IIIa in the closure group (P=0.02 and 0.04, respectively).
      Regarding the Wexner score, there was no significant difference between the two
      groups (P=0.24). Compared with the closure group, the non-closure group had
      significantly fewer postoperative complications of all grades and >=Clavien-Dindo
      grade IIIa. Moreover, there was no significant difference regarding the anorectal
      function between the two groups. Thus, suturing the rectal defect is not
      necessarily recommended following TAE.

PMID- 27699043
TI  - Comparative safety of BRAF and MEK inhibitors (vemurafenib, dabrafenib and
      trametinib) in first-line therapy for BRAF-mutated metastatic melanoma.
AB  - A retrospective observational study was conducted on patients diagnosed with
      serine/threonine-protein kinase B-Raf (BRAF)-mutated metastatic melanoma, who
      underwent first-line therapy with BRAF and mitogen-activated protein kinase
      kinase (MEK) inhibitors (vemurafenib, dabrafenib or a combination of dabrafenib
      and trametinib) at the Miguel Servet University Hospital (Zaragoza, Spain)
      between November, 2011 and August, 2015. The aim of this study was to analyse the
      toxicity produced by BRAF and MEK inhibitors. The most common toxicities were
      similar to those published in clinical trials, particularly arthralgia, alopecia
      and photosensitivity in the vemurafenib group; asthenia, hyperkeratosis and dry
      skin in the dabrafenib group; and diarrhoea and dry skin in the dabrafenib plus
      trametinib group. Toxicities that had not been described in clinical trials were
      also identified. Thus, the present study confirmed that the results obtained in
      clinical trials are similar to those obtained in clinical practice.

PMID- 27699044
TI  - Partial response to chemotherapy in a patient with retroperitoneal inflammatory
      myofibroblastic tumor.
AB  - Retroperitoneal inflammatory myofibroblastic tumor (IMT) is a rare lesion of
      unknown etiology. The management of IMT may be challenging due to its
      intermediate malignant potential, the possibility of local recurrence after
      surgical resection and its unique anatomic location, which makes radical
      resection impossible due to its proximity to vital structures. Thus, treatment
      for recurrence and metastasis mainly relies on chemotherapy. We herein report a
      case of a 60-year-old man with an IMT sized 6.7*5.1 cm, located in the left
      adrenal area, which was identified by a computed tomography (CT) scan of the
      abdomen. Radical surgical resection of the tumor was not feasible, as it was
      fixed to the left renal artery. After 5 months, the patient underwent CT-guided
      radiofrequency ablation of the re-growing tumor. An unresectable mass was
      detected in the patient's rectum by a CT scan of the pelvis. Subsequently, the
      patient underwent chemotherapy for the recurring and metastatic tumors. The
      chemotherapeutic regimens included epirubicin, dacarbazine and docetaxel. Over
      the last 6 months, after three cycles of therapy, the sizes of the primary and
      metastatic tumors had decreased on the follow-up CT scan. Thus, chemotherapy
      effectively controlled the disease in this case, following unsuccessful surgical
      resection and radiofrequency ablation. The present case report highlights the
      complexity of treatment in such cases and the significance of designing a
      clinical protocol for the treatment of IMT.

PMID- 27699045
TI  - Common carotid artery dissection caused by radiotherapy: A case report.
AB  - In the present study, a case of acute cerebral infarction with radiation-induced
      carotid artery dissection is reported. Carotid artery dissection is generally
      asymptomatic at the early stages. Due to the non-specific clinical manifestations
      of carotid artery dissection, a detailed inquiry of the past history of a patient
      has a critical role in making a diagnosis of radiation-induced common carotid
      artery dissection. Onset of acute ischemic stroke is the predominant
      manifestation, and for patients with a history of head-and-neck radiotherapy,
      dissection should be considered. The condition may progress rapidly, and result
      in a poor prognosis. Therefore, a correct early diagnosis and initiation of
      appropriate therapy may lead to rapid recovery, and influence the overall
      prognosis.

PMID- 27699046
TI  - Lower limb lymphedema in lung adenocarcinoma: Two case reports.
AB  - Breast and gynecological cancers and their treatment may cause lymphedema of the
      upper and lower extremities, respectively. We herein report the cases of two
      patients with lung adenocarcinoma who developed lymphedema of the lower
      extremities. One patient harbored an epidermal growth factor receptor mutation
      and the other patient harbored an anaplastic lymphoma kinase fusion gene. The
      patients had developed intra-abdominal lymph node metastases and received several
      lines of chemotherapy. In both patients, lymphedema in the lower extremities
      developed >30 months after the initiation of first-line chemotherapy. To the best
      of our knowledge, these are the first reported cases of lung cancer patients who
      developed lymphedema in the lower extremities. Although rarely, lymphedema of the
      lower extremities may develop long after successful therapy with molecular
      targeted therapy in advanced lung adenocarcinoma patients with a specific genetic
      etiological background.

PMID- 27699047
TI  - Hypersomnia as the first presentation in a patient with insulinoma: A case report
      and review of the literature.
AB  - Insulinoma is a rare neuroendocrine tumor. Hypersomnia as the first presentation
      in a patient with insulinoma is even more rare and may be easy to misdiagnose. We
      are herein reporting a case of insulinoma initially presenting with prolonged
      sleep time and extreme difficulty in waking. The abovementioned symptoms occurred
      every 2-3 months. Over the last 2 months, the attacks had become more frequent
      and severe. On computed tomography examination, a 12*9-mm cystic nodule was
      detected in the uncinate process of the pancreas, which was pathologically
      diagnosed as insulinoma. Since resection, the symptom of hypersomnia has not
      occurred again. The aim of the present report was to raise awareness among
      physicians to consider insulinoma in the differential diagnosis of hypersomnia in
      patients without other known diseases.

PMID- 27699049
TI  - "Lachnoclostridium touaregense," a new bacterial species isolated from the human
      gut microbiota.
AB  - We report the main characteristics of "Lachnoclostridium touaregense" strain
      Marseille-P2415T (= CSUR P2415 = DSM 102219), a new bacterial species isolated
      from the gut microbiota of a healthy young girl from Niger.

PMID- 27699050
TI  - "Lagierella massiliensis," a new bacterium detected in human feces.
AB  - We report here the main characteristics of "Lagierella massiliensis" strain SIT14
      (CSUR P2012), which was isolated from a stool specimen from a healthy 28-month
      old Senegalese boy.

PMID- 27699048
TI  - Successful treatment of non-small-cell lung cancer with afatinib and a
      glucocorticoid following gefitinib- and erlotinib-induced interstitial lung
      disease: A case report.
AB  - Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-induced
      interstitial lung disease (ILD) may be a life-threatening condition that may
      develop during treatment of lung cancer patients harboring EGFR mutations. We
      herein present the case of a 41-year-old female patient diagnosed with lung
      adenocarcinoma with an EGFR mutation (exon 19 deletion). The patient was treated
      with gefitinib followed by erlotinib and developed ILD induced by both EGFR-TKIs;
      furthermore, the patient acquired resistance to EGFR-TKI treatment. A repeat
      biopsy revealed a T790M mutation, which is associated with resistance to first
      generation EGFR-TKIs, along with an exon 19 deletion identified by cytology of
      the pleural fluid. Treatment with afatinib and prednisolone resulted in tumor
      shrinkage, without worsening of the ILD. The present case demonstrated that
      combination treatment with afatinib and a glucocorticoid may be effective for the
      treatment of lung cancer patients who develop EGFR-TKI-induced ILD.

PMID- 27699051
TI  - "Anaerotruncus massiliensis," a new species identified from human stool from an
      obese patient after bariatric surgery.
AB  - We report the main characteristics of a new bacterial species strain AT3T (CSUR =
      P2007, DSM = 100567) that was isolated from the stool sample collected from a 47
      year-old obese French man after he underwent bariatric surgery.

PMID- 27699052
TI  - Induction treatment of previously undiagnosed ANCA-associated vasculitis in a
      renal transplant patient with Rituximab.
AB  - We report the case of a 40-year-old female transplant patient with undiagnosed
      ANCA-associated vasculitis (AAV) and renal allograft dysfunction who achieved
      disease remission with restoration of transplant function following induction
      therapy with rituximab. There are currently no trial data looking at the use of
      rituximab for induction of remission of renal transplant patients with AAV.
      Although recurrence of AAV following renal transplantation is rare, such patients
      have invariably had multiple previous exposures to induction and maintenance
      immunosuppressive regimens, often limiting treatment options post
      transplantation. In this case, rituximab was well tolerated with no side effects,
      and was successful in salvaging transplant function. Optimal treatment regimens
      for relapsed AAV in the transplant population are not known, and clinical trials
      are needed to evaluate the efficacy and safety of rituximab at inducing and
      maintaining disease remission in relapsed AAV following transplantation.

PMID- 27699054
TI  - Opsoclonus-myoclonus-ataxia syndrome in an HIV-infected child.
AB  - Opsoclonus-myoclonus-ataxia (OMA) syndrome typically presents with chaotic eye
      movements and myoclonus with some patients exhibiting ataxia and behavioural
      disturbances. The pathogenesis may be inflammatory with an infectious or
      paraneoplastic trigger. We present a 13-year-old HIV-infected girl who was
      initially started on highly active antiretroviral therapy (HAART) in March 2013
      with a CD4 count of 79 cells/cumm. Initially, the patient did not comply with
      treatment, resulting in a CD4+ count of 77 cells/mm3 in November 2015 and
      prompting a new HAART scheme comprising lamivudine, tenofovir and ritonavir
      boosted atazanavir. Shortly after starting this scheme, she developed OMA
      syndrome in January 2016. She was treated with intravenous immunoglobulin and
      methylprednisolone followed by oral steroids along with oral clonazepam and
      gradually recovered. We suggest immune reconstitution inflammatory syndrome as a
      possible aetiology of OMA in HIV-infected children.

PMID- 27699053
TI  - Lessons from treatment resistant hyperlipidaemia.
AB  - A 68-year-old woman was referred to Lipid Clinic with sudden deterioration of
      previously well-controlled primary hyperlipidaemia. Investigations revealed
      nephrotic range proteinuria, leading to urgent renal biopsy and a diagnosis of
      amyloidosis. Chemotherapy was successful in stabilising renal function, reducing
      proteinuria and eliminating serum paraprotein. The resistant hyperlipidaemia
      subsequently resolved. Whilst hyperlipidaemia is pathognomonic of nephrotic
      syndrome, it is rarely the first characteristic identified by clinicians, often
      preceded by the identification of oedema or proteinuria. This case is an unusual
      example of a nephrotic syndrome presenting to Lipid Clinic as a resistant primary
      hyperlipidaemia, and highlights the importance of considering superimposed
      secondary causes of hyperlipidaemia in treatment resistant cases.

PMID- 27699055
TI  - A rare presentation of spontaneous internal carotid artery dissection with
      Horner's syndrome, VIIth, Xth and XIIth nerve palsies.
AB  - Spontaneous internal carotid artery dissection (sICAD) is an uncommon cause of
      isolated cranial nerve palsies. Commonly patients present with stroke, headache,
      facial pain and Horner's syndrome, with upto 16% having cranial nerve palsies. We
      present the case of a 55-year-old man who presented with hoarseness, dysphagia
      and tongue swelling, mimicking a tongue base tumor. He was found to have
      unilateral VIIth, Xth and XIIth nerve palsies with Horner's syndrome. Magnetic
      resonance imaging showed high signal changes and loss of signal void in right
      internal carotid artery, later confirmed by Angiography as a dissection with
      pseudo-aneurysm. He was started on anticoagulation and made a good recovery on
      discharge. This case presents a unique combination of cranial nerve palsies due
      to internal carotid artery dissection (ICAD) and to our knowledge is the first
      reported case in the literature. Early recognition and institution of appropriate
      therapy is critical to prevention of ischemic stroke.

PMID- 27699056
TI  - Management of anthracycline extravasation into the pleural space.
AB  - Anthracycline extravasation is a feared complication of intravenous (i.v.)
      chemotherapy due to the tissue toxicity of this group of drugs. We describe a 54
      year-old woman with history of stage IIIa breast cancer, receiving adjuvant
      chemotherapy consisting of doxorubicin and cyclophosphamide. The chemotherapy was
      administered through a Poweport(r) device, the position of which was confirmed
      with fluoroscopy and function confirmed by flushing the line. Urgent intervention
      was required as patient was symptomatic and experienced severe right-sided
      pleuritic chest pain. Radiology also confirmed the extravasation of doxorubicin
      into the pleural space. Surgical washout of the pleural space and 3 days therapy
      with i.v. dexrazoxane were carried out to prevent tissue damage and long-term
      sequelae. Use of dexrazoxane should always be considered following intra-pleural
      extravasation because of its potential efficacy and reasonable tolerability.
      However, the best approach to extravasation injury is prevention by systematic
      implementation of careful, standardized, evidence-based administration
      techniques.

PMID- 27699057
TI  - Controlling the strontium-doping in calcium phosphate microcapsules through yeast
      regulated biomimetic mineralization.
AB  - Yeast cells have controllable biosorption on metallic ions during metabolism.
      However, few studies were dedicated to using yeast-regulated biomimetic
      mineralization process to control the strontium-doped positions in calcium
      phosphate microcapsules. In this study, the yeast cells were allowed to pre
      adsorb strontium ions metabolically and then served as sacrificing template for
      the precipitation and calcination of mineral shell. The pre-adsorption enabled
      the microorganism to enrich of strontium ions into the inner part of the
      microcapsules, which ensured a slow-release profile of the trace element from the
      microcapsule. The co-culture with human marrow stromal cells showed that gene
      expressions of alkaline phosphatase and Collagen-I were promoted. The promotion
      of osteogenic differentiation was further confirmed in the 3D culture of cell
      material complexes. The strategy using living microorganism as 'smart doping
      apparatus' to control incorporation of trace element into calcium phosphate paved
      a pathway to new functional materials for hard tissue regeneration.

PMID- 27699058
TI  - Stability research on polydopamine and immobilized albumin on 316L stainless
      steel.
AB  - In this study, the polydopamine (PDA) film was coated on polished 316Lss and then
      thermally treated at 150  degrees C (labeled as PDA-Th150), and the stability of
      coatings was also investigated. Straining test indicated that PDA-Th150 coating
      performed better in affording sufficient adherence to 316 L SS substrate.
      Moreover, both PDA and PDA-Th150 coating suffered slight swelling during
      immersion in deionized water (pH = 6.5). X-ray photoelectron spectroscopy results
      showed that during immersion, latent nucleophilic reaction via amines inside PDA
      coating occurred. This led to an enhanced cross-linking and thus gradually
      promoted the coating stability. Moreover, larger amount of bovine serum albumin
      (BSA) was immobilized onto PDA-Th150 coating and performed well in anti-platelet
      adhesion. A high retention of immobilized BSA was observed even after immersion
      for 30 days. These tests suggested that PDA was stable enough and performed well
      in surface functionalization, which might enrich the research and application of
      PDA.

PMID- 27699059
TI  - Ectopic osteogenesis and angiogenesis regulated by porous architecture of
      hydroxyapatite scaffolds with similar interconnecting structure in vivo.
AB  - The macro-pore sizes of porous scaffold play a key role for regulating ectopic
      osteogenesis and angiogenesis but many researches ignored the influence of
      interconnection between macro-pores with different sizes. In order to accurately
      reveal the relationship between ectopic osteogenesis and macro-pore sizes in
      dorsal muscle and abdominal cavities of dogs, hydroxyapatite (HA) scaffolds with
      three different macro-pore sizes of 500-650, 750-900 and 1100-1250 um were
      prepared via sugar spheres-leaching process, which also had similar
      interconnecting structure determined by keeping the d/s ratio of interconnecting
      window diameter to macro-pore size constant. The permeability test showed that
      the seepage flow of fluid through the porous scaffolds increased with the
      increase of macro-pore sizes. The cell growth in three scaffolds was not affected
      by the macro-pore sizes. The in vivo ectopic implantation results indicated that
      the macro-pore sizes of HA scaffolds with the similar interconnecting structure
      have impact not only the speed of osteogenesis and angiogenesis but also the
      space distribution of newly formed bone. The scaffold with macro-pore sizes of
      750-900 um exhibited much faster angiogenesis and osteogenesis, and much more
      uniformly distribution of new bone than those with other macro-pore sizes. This
      work illustrates the importance of a suitable macro-pore sizes in HA scaffolds
      with the similar interconnecting structure which provides the environment for
      ectopic osteogenesis and angiogenesis.

PMID- 27699060
TI  - Efficient GSH delivery using PAMAM-GSH into MPP-induced PC12 cellular model for
      Parkinson's disease.
AB  - Glutathione (GSH) depletion has been an important contributor to the dysfunction
      of dopamine neurons. Polyamidoamine-GSH (PAMAM-GSH) was synthesized and the
      delivery effect of GSH into PC12 cells was tested. MTT assessment for
      cytotoxicity and reactive oxygen species (ROS) as well as nitrite oxide (NO) and
      intracelluar superoxide dismutase (SOD) detection for antioxidative ability were
      performed. Furthermore, the antiapoptotic ability was analysed by assessing
      caspase-3, JNK1/2 and Erk1/2 expression. Our data indicated that PAMAM-GSH is an
      effective agent to replenish GSH into PC12 cells. PAMAM-GSH developed its
      antioxidative and protective ability for 1-methyl-4-phenylpyridinium (MPP)
      induced PC12 cells by reducing the intracellular levels of ROS and SOD activity
      as well as decreasing the release of NO. Meanwhile, PAMAM-GSH could inhibit
      caspase-3 activation and might show its antiapoptotic ability to MPP-induced PC12
      cells through JNK2/Erk1/2 pathway. In summary, these studies suggest that PAMAM
      GSH conjugate has an intrinsic ability to penetrate PC12 cells and deliver GSH
      into these cells which may provide a new strategy for clinical applications in
      the treatment of Parkinson's disease.

PMID- 27699061
TI  - Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with
      controlled release behavior.
AB  - The development of modern therapeutics has raised the requirement for controlled
      drug delivery system which is able to efficiently encapsulate bioactive agents
      and achieve their release at a desired rate satisfying the need of the practical
      system. In this study, two kind of aqueous model drugs with different molecule
      weight, Congo red and albumin from bovine serum (BSA) were nano-encapsulated in
      poly (dl-lactic-co-glycolic acid) (PLGA) microspheres by emulsion electrospray.
      In the preparation process, the aqueous phase of drugs was added into the PLGA
      chloroform solution to form the emulsion solution. The emulsion was then
      electrosprayed to fabricate drug-nanoencapsulated PLGA microspheres. The
      morphology of the PLGA microspheres was affected by the volume ratio of aqueous
      drug phase and organic PLGA phase (Vw/Vo ) and the molecule weight of model
      drugs. Confocal laser scanning microcopy showed the nanodroplets of drug phase
      were scattered in the PLGA microspheres homogenously with different distribution
      patterns related to Vw/Vo . With the increase of the volume ratio of aqueous drug
      phase, the number of nanodroplets increased forming continuous phase gradually
      that could accelerate drug release rate. Moreover, BSA showed a slower release
      rate from PLGA microspheres comparing to Congo red, which indicated the drug
      release rate could be affected by not only Vw/Vo but also the molecule weight of
      model drug. In brief, the PLGA microspheres prepared using emulsion electrospray
      provided an efficient and simple system to achieve controlled drug release at a
      desired rate satisfying the need of the practices.

PMID- 27699062
TI  - Comparison of safety and efficiency of microendoscopic discectomy with automatic
      nerve retractor and with nerve hook.
AB  - This study compares the safety and efficiency of two techniques in
      microendoscopic discectomy (MED) for lumbar disc herniation. The two techniques
      are MED with automatic nerve retractor and MED with nerve hook which had been
      widely used for many years. The former involves a newly developed MED device
      which contains three parts to protect nerve roots during operation. Four hundred
      and twenty-eight patients underwent MED treatments between October 2010 and
      September 2015 were recruited and randomized to either intraoperative utilization
      of automatic nerve retractor (n = 315, group A) or application of nerve hook
      during surgery (n = 113, group B). Operation time and intraoperative bleeding
      volume were evaluated. Simultaneously, Visual Analogue Scales (VAS) and muscle
      strength grading were performed preoperatively, and 1, 2, 3 days, 1, 2 weeks, 3
      and 6 months postoperatively. No dramatic difference of pain intensity was
      observed between the two groups before surgery and 6 months after surgery (P >
      0.05). The operation time was shorter in group A (30.30 +/- 1.89 min) than that
      in group B (59.41 +/- 3.25 min). Group A (67.83 +/- 13.14 ml) experienced a
      significant decrease in the amount of blood loss volume when compared with group
      B (100.04 +/- 15.10 ml). There were remarkable differences of VAS score and
      muscle strength grading after postoperative 1, 2, 3 days, 1, 2 weeks and 3 months
      between both groups (P <= 0.05). MED with automatic nerve retractor effectively
      shortened operation time, decreased the amount of bleeding, down-regulated the
      incidence of nerve traction injury.

PMID- 27699064
TI  - Comment on "Choroidal Thickness in Patients with Mild Cognitive Impairment and
      Alzheimer's Type Dementia".

PMID- 27699063
TI  - Determining the critical size of a rabbit rib segmental bone defect model.
AB  - In order to establish and standardize the rabbit rib segmental bone defect model,
      it is of vital importance to determine rabbit rib critical size defect (CSD).
      According to the general time needed for spontaneous long-bone regeneration,
      three-month observation period was set to determine the CSD. The rabbit rib
      segmental bone defects with different sizes from 1 to 5 cm with or without
      periosteum were performed in the eighth rib of 4-month-old male New Zealand
      rabbits and underwent X-ray examinations at the 4th, 8th and 12th weeks
      postoperatively. The gross and histological examinations at postoperative week 12
      were evaluated, which showed that the critical sizes in the rabbit rib models
      with and without periosteum were 5 and 2 cm, respectively. This study provides
      prerequisite data for establishing rabbit rib CSD model and evaluating bone
      materials using this model.

PMID- 27699066
TI  - Efficient BinDCT hardware architecture exploration and implementation on FPGA.
AB  - This paper presents a hardware module design for the forward Binary Discrete
      Cosine Transform (BinDCT) and its implementation on a field programmable gate
      array device. Different architectures of the BinDCT module were explored to
      ensure the maximum efficiency. The elaboration of these architectures included
      architectural design, timing and pipeline analysis, hardware description language
      modeling, design synthesis, and implementation. The developed BinDCT hardware
      module presents a high efficiency in terms of operating frequency and hardware
      resources, which has made it suitable for the most recent video standards with
      high image resolution and refresh frequency. Additionally, the high hardware
      efficiency of the BinDCT would make it a very good candidate for time and
      resource-constrained applications. By comparison with several recent
      implementations of discrete cosine transform approximations, it has been shown
      that the proposed hardware BinDCT module presents the best performances.

PMID- 27699067
TI  - General expressions for downlink signal to interference and noise ratio in
      homogeneous and heterogeneous LTE-Advanced networks.
AB  - The interference is the most important problem in LTE or LTE-Advanced networks.
      In this paper, the interference was investigated in terms of the downlink signal
      to interference and noise ratio (SINR). In order to compare the different
      frequency reuse methods that were developed to enhance the SINR, it would be
      helpful to have a generalized expression to study the performance of the
      different methods. Therefore, this paper introduces general expressions for the
      SINR in homogeneous and in heterogeneous networks. In homogeneous networks, the
      expression was applied for the most common types of frequency reuse techniques:
      soft frequency reuse (SFR) and fractional frequency reuse (FFR). The expression
      was examined by comparing it with previously developed ones in the literature and
      the comparison showed that the expression is valid for any type of frequency
      reuse scheme and any network topology. Furthermore, the expression was extended
      to include the heterogeneous network; the expression includes the problem of co
      tier and cross-tier interference in heterogeneous networks (HetNet) and it was
      examined by the same method of the homogeneous one.

PMID- 27699065
TI  - Appetite Suppression and Antiobesity Effect of a Botanical Composition Composed
      of Morus alba, Yerba mate, and Magnolia officinalis.
AB  - Background. Obesity and its comorbidities continue to challenge the world at an
      alarming rate. Although the long term solution lies on lifestyle changes in the
      form of dieting and exercising, drug, medical food, or dietary supplement
      interventions are required for those who are already obese. Here we describe a
      standardized blend composed of extracts from three medicinal plants: Morus alba,
      Yerba mate, and Magnolia officinalis for appetite suppression and metabolic
      disorders management. Method. Extracts were standardized to yield a composition
      designated as UP601. Appetite suppression activity was tested in acute feed
      intake rat model. Efficacy was evaluated in C57BL/6J mouse models treated with
      oral doses of 1.3 g/kg/day for 7 weeks. Orlistat at 40 mg/kg/day was used as a
      positive control. Body compositions of mice were assessed using a dual energy X
      ray absorptiometry (DEXA). ELISA was done for insulin, leptin, and ghrelin level
      quantitation. Nonalcoholic steatohepatitis (NASH) scoring was conducted. Results.
      Marked acute hypophagia with 81.8, 75.3, 43.9, and 30.9% reductions in food
      intake at 2, 4, 6, and 24 hours were observed for UP601. Decreases in body weight
      gain (21.5% compared to the HFD at weeks 7 and 8.2% compared to baseline) and
      calorie intake (40.5% for the first week) were observed. 75.9% and 46.8%
      reductions in insulin and leptin, respectively, 4.2-fold increase in ghrelin
      level, and reductions of 18.6% in cholesterol and 59% in low-density lipoprotein
      were documented. A percentage body fat of 18.9%, 47.8%, 46.1%, and 30.4% was
      found for mice treated with normal control, HFD, Orlistat, and UP601,
      respectively. 59.3% less mesenteric fat pad and improved NASH scores were
      observed for UP601. Conclusion. UP601, a standardized botanical composition from
      Morus alba, Yerba mate, and Magnolia officinalis could be used as a natural
      alternative for appetite suppression, maintaining healthy body weight and
      metabolism management.

PMID- 27699068
TI  - Validation Protocol of Vitamin D Supplementation in Patients with HIV-Infection.
AB  - Hypovitaminosis D and secondary hyperparathyroidism are frequent among HIV
      infected patients. As there are no data about the best supplementation therapy
      both in treatment and in maintenance, we conducted an observational study of 300
      HIV-infected patients for whom vitamin D and parathormone (PTH) had been measured
      in order to validate a protocol of vitamin D supplementation in patients with HIV
      infection. Patients with vitamin D deficiency (defined as 25(OH)D < 10 ng/mL),
      insufficiency (defined as 25(OH)D < 20 ng/mL), or hyperparathyroidism (PTH > 65
      pg/mL) were supplemented with cholecalciferol 16.000IU (0.266 mg) weekly (if
      deficiency) or fortnightly (if insufficiency or high PTH levels). Rates of
      normalization of 25(OH)D (levels above 20 ng/mL) and PTH levels (<65 pg/mL) were
      analyzed. Multivariate analysis of factors related to normalization was carried
      out. With a median follow-up of 2 years, 82.1% of patients with deficiency and
      83.9% of cases with insufficiency reached levels above 20 ng/mL. However, only
      67.2% of individuals with hyperparathyroidism at baseline reached target levels
      (<65 pg/mL). Independent factors for not achieving PTH objective were tenofovir
      (TDF) and protease inhibitors use. In HIV-infected patients with hypovitaminosis,
      the protocol of cholecalciferol supplementation normalized vitamin D levels
      regardless of antiretroviral regimen in a high proportion of patients but it was
      less effective to correct hyperparathyroidism.

PMID- 27699069
TI  - Personality Traits in College Students and Caregiving for a Relative with a
      Chronic Health Condition.
AB  - The purpose of this study was to investigate among college students the
      relationship between personality traits and willingness to care for a relative
      with a chronic health condition. 329 undergraduate students completed an online
      questionnaire. Hierarchical multiple regressions found that after controlling for
      demographics personality traits explained 10% of the variance in willingness to
      provide emotional care, 7% in instrumental care, and 7% in nursing care. Within
      these models, greater empathy was uniquely associated with willingness to provide
      emotional, instrumental, and nursing care for a family member in the future.
      Similarly, participants with high agreeableness were more willing to provide
      emotional care, and participant older age was a unique predictor of instrumental
      care. The results can help shape research on interventions that incorporate
      perspective taking, motivational interviewing, and training in life skills as a
      means of boosting college students' willingness to provide care for a relative
      with a chronic health condition.

PMID- 27699070
TI  - Effect of Purified Mushroom Tyrosinase on Melanin Content and Melanogenic Protein
      Expression.
AB  - In mammalian melanocytes, melanosome is a highly specialized organelle where
      melanin is synthesized. Melanin synthesis is controlled by tyrosinase, the vital
      enzyme in melanogenic pathway. The present investigation is based on an effect of
      purified mushroom tyrosinase of Agaricus bisporus on B16F10 melanocytes for the
      melanin production via blocking pigment cell machinery. Using B16F10 melanocytes
      showed that the stimulation of melanogenesis by purified tyrosinase is due to
      increased tyrosinase absorption. Cellular tyrosinase activity and melanin content
      in B16F10 melanocytes were increased by purified tyrosinase in a dose-dependent
      manner. Western blot analysis revealed that cellular tyrosinase levels were
      enhanced after treatment with purified tyrosinase for 48 hours. Furthermore,
      tyrosinase induced phosphorylation of cyclic adenosine monophosphate (cAMP)
      response element-binding protein (CREB) in a dose-dependent manner. The purified
      tyrosinase-mediated increase of tyrosinase activity was significantly attenuated
      by H89, LY294002, Ro-32-0432, and PD98059, cAMP-dependent protein kinase
      inhibitors. The results indicate that purified tyrosinase can be used as
      contestant for the treatment of vitiligous skin conditions.

PMID- 27699071
TI  - A Rare Case of Persistent Lactic Acidosis in the ICU: Glycogenic Hepatopathy and
      Mauriac Syndrome.
AB  - Mauriac syndrome is a rare disorder that can present with the single feature of
      glycogenic hepatopathy in children and adults with poorly controlled diabetes
      mellitus. An often underrecognized finding of glycogenic hepatopathy is lactic
      acidosis and hyperlactatemia. Primary treatment of glycogenic hepatopathy is
      improved long-term blood glucose control. Resolution of symptoms and hepatomegaly
      will occur with improvement in hemoglobin A1C. We present here a case of a young
      adult female presenting to the intensive care unit with Mauriac syndrome. This
      case demonstrates exacerbation of lactic acidosis in a patient with glycogenic
      hepatopathy treated for diabetic ketoacidosis with high dose insulin and
      dextrose.

PMID- 27699072
TI  - Two-Step Extraction of the Lower First Molar for Class III Treatment in Adult
      Patient.
AB  - The aim of this article is to describe a case report of Class III malocclusion
      treatment with lower first molar extraction. The 27-year-old Caucasian male
      patient presented a symmetric face with a straight profile, hyperdivergent growth
      pattern, molar and cuspid Class III relation, and an anterior crossbite as well
      as a mild crowding on cuspids area, in both upper and lower arches and a tendency
      to posterior crossbite. The treatment was performed by the use of Haas expansion
      appliance followed by an initial alignment and leveling of the upper and lower
      arches with a fixed edgewise appliance, extraction of lower teeth aiming the
      correction of the incisors proclination and end the treatment with a Class I
      molar relationship. It resulted in a significant change in the patient's profile,
      dentoalveolar Class III correction, upper arch expansion, leveling and alignment
      of the upper and lower arches, and improvement of tipping of the upper and lowers
      incisors. In cases of a dentoalveolar compensation in well positioned bone bases
      the treatment with fixed appliances is an alternative and extraction of lower
      teeth is considered.

PMID- 27699073
TI  - Early Diagnosis and Hematopoietic Stem Cell Transplantation for IL10R Deficiency
      Leading to Very Early-Onset Inflammatory Bowel Disease Are Essential in Familial
      Cases.
AB  - Alterations of immune homeostasis in the gut may result in development of
      inflammatory bowel disease. A five-month-old girl was referred for recurrent
      respiratory and genitourinary tract infections, sepsis in neonatal period,
      chronic diarrhea, perianal abscess, rectovaginal fistula, and hyperemic skin
      lesions. She was born to second-degree consanguineous, healthy parents. Her elder
      siblings were lost at 4 months of age due to sepsis and 1 year of age due to
      inflammatory bowel disease, respectively. Absolute neutrophil and lymphocyte
      counts, immunoglobulin levels, and lymphocyte subsets were normal ruling out
      severe congenital neutropenia and classic severe combined immunodeficiencies.
      Quantitative determination of oxidative burst was normal, excluding chronic
      granulomatous disease. Colonoscopy revealed granulation, ulceration, and
      pseudopolyps, compatible with colitis. Very early-onset colitis and perianal
      disease leading to fistula formation suggested probability of inherited
      deficiencies of IL-10 or IL-10 receptor. A mutation at position c.G477A in exon
      of the IL10RB gene, resulting in a stop codon at position p.W159X, was
      identified. The patient underwent myeloablative hematopoietic stem cell
      transplantation from full matched father at 11 months of age. Perianal lesions,
      chronic diarrhea, and recurrent infections resolved after transplantation. IL
      10/IL-10R deficiencies must be considered in patients with early-onset
      enterocolitis.

PMID- 27699074
TI  - Successful Treatment of Uterine Arteriovenous Malformation due to Uterine Trauma.
AB  - Uterine arteriovenous malformation (AVM) is defined as abnormal and nonfunctional
      connections between the uterine arteries and veins. Although the patients
      typically present with vaginal bleeding, some patients may experience life
      threatening massive bleeding in some circumstances. The treatment of choice
      depends on the symptoms, age, desire for future fertility, and localization and
      size of the lesion; however, embolization of the uterine artery is the first
      choice in symptomatic AVM in patients at reproductive age with expectations of
      future fertility. We report a case of acquired AVM (after D/C) with an extensive
      lesion, which was successfully treated with bilateral uterine artery embolization
      (UAE).

PMID- 27699075
TI  - Pleomorphic Rhabdomyosarcoma Arising from True Vocal Fold of Larynx: Report of a
      Rare Case and Literature Review.
AB  - We present an extremely rare case of a pleomorphic rhabdomyosarcoma of the true
      vocal fold. The histopathological diagnosis was confirmed by
      immunohistochemistry. The patient was treated with radical surgery including
      total laryngectomy and radical neck dissection followed by postoperative
      radiotherapy. The clinicopathologic features of this rare malignancy are
      discussed together with a review of the literature. This case report and
      literature review highlights the more favorable prognosis of pleomorphic
      rhabdomyosarcoma in the larynx than in other locations.

PMID- 27699076
TI  - Heparin-Related Thrombocytopenia Triggered by Severe Status of Systemic Lupus
      Erythematosus and Bacterial Infection.
AB  - A patient with severe lupus nephritis developed thrombocytopenia during treatment
      with high-dose steroids. In addition to viral- or disease-induced cytopenia, the
      pathology was believed to arise from diverse contributing factors, such as
      thrombotic microangiopathy and heparin-related thrombocytopenia (HIT). By
      combining plasma exchange therapy and intravenous cyclophosphamide, we
      successfully controlled the SLE activity and improved the thrombocytopenia. An
      antecedent bacterial infection or SLE activity is believed to have contributed to
      the concurrent HIT.

PMID- 27699077
TI  - A Case of Successful Coil Embolization for a Late-Onset Type Ia Endoleak after
      Endovascular Aneurysm Repair with the Chimney Technique.
AB  - Juxtarenal aortic aneurysms (JRAAs) are challenging to treat by endovascular
      aneurysm repair (EVAR) procedures. The chimney technique with EVAR (Ch-EVAR) is
      one of the feasible and less invasive treatments for JRAAs. However, the main
      concern of Ch-EVAR is the potential risk of "gutters," which can lead to type Ia
      endoleak (EL). Most type Ia ELs after Ch-EVAR procedures occurred
      intraoperatively, and these ELs could be treated using an endovascular technique.
      However, late-onset type Ia ELs could be extremely rare, which might have a fear
      of conservative treatment. Type Ia ELs are associated with an increased risk of
      aneurysm rupture; therefore reintervention is recommended as soon as possible,
      and we should be aware of the occurrence of type Ia ELs after the Ch-EVAR
      procedure.

PMID- 27699078
TI  - Exposure to Persistent Organic Pollutants Predicts Telomere Length in Older Age:
      Results from the Helsinki Birth Cohort Study.
AB  - As the population ages, the occurrence of chronic pathologies becomes more
      common. Leukocyte telomere shortening associates to ageing and age-related
      diseases. Recent studies suggest that environmental chemicals can affect telomere
      length. Persistent organic pollutants (POPs) are most relevant, since they are
      ingested with foods, and accumulate in the body for a long time. This
      longitudinal study was undertaken to test if circulating POPs predict telomere
      length and shortening in elderly people. We studied 1082 subjects belonging to
      the Helsinki Birth Cohort Study (born 1934-1944), undergoing two visits (2001
      2004 and 2011-2014). POPs (oxychlordane, trans-nonachlor, p, p'-DDE, PCB 153, BDE
      47, BDE 153) were analysed at baseline. Relative telomere length was measured
      twice, '10 years apart, by quantitative real-time PCR. Oxychlordane, trans
      nonachlor and PCB-153 levels were significant predictors of telomere length and
      shortening. In men, we did not find a linear relationship between POPs exposure
      and telomere shortening. In women, a significant reduction across quartiles
      categories of oxychlordane and trans-nonachlor exposure was observed. Baseline
      characteristics of subjects in the highest POPs categories included higher levels
      of C-reactive protein and fasting glucose, and lower body fat percentage. This is
      one of few studies combining POPs and telomere length. Our results indicate that
      exposure to oxychlordane, trans-nonachlor and PCB 153 predicts telomere
      attrition. This finding is important because concentrations of POPs observed here
      occur in contemporary younger people, and may contribute to an accelerated
      ageing.

PMID- 27699079
TI  - Education and Genetic Risk Modulate Hippocampal Structure in Alzheimer's Disease.
AB  - Genetic and environmental protective factors and risks modulate brain structure
      and function in neurodegenerative diseases and their preclinical stages. We
      wanted to investigate whether the years of formal education, a proxy measure for
      cognitive reserve, would influence hippocampal structure in Alzheimer's disease
      patients, and whether apolipoprotein Eepsilon4 (APOE4) carrier status and a first
      degree family history of the disease would change a possible association. Fifty
      eight Alzheimer's disease patients underwent 3T magnetic resonance imaging. We
      applied a cortical unfolding approach to investigate individual subregions of the
      medial temporal lobe. Among patients homozygous for the APOE4 genotype or
      carrying both APOE4 and family history risks, lower education was associated with
      a thinner cortex in multiple medial temporal regions, including the hippocampus.
      Our data suggest that the years of formal education and genetic risks interact in
      their influence on hippocampal structure in Alzheimer's disease patients.

PMID- 27699080
TI  - Brain Formaldehyde is Related to Water Intake behavior.
AB  - A promising strategy for the prevention of Alzheimer's disease (AD) is the
      identification of age-related changes that place the brain at risk for the
      disease. Additionally, AD is associated with chronic dehydration, and one of the
      significant changes that are known to result in metabolic dysfunction is an
      increase in the endogenous formaldehyde (FA) level. Here, we demonstrate that the
      levels of uric formaldehyde in AD patients were markedly increased compared with
      normal controls. The brain formaldehyde levels of wild-type C57 BL/6 mice
      increased with age, and these increases were followed by decreases in their
      drinking frequency and water intake. The serum arginine vasopressin (AVP)
      concentrations were also maintained at a high level in the 10-month-old mice. An
      intravenous injection of AVP into the tail induced decreases in the drinking
      frequency and water intake in the mice, and these decreases were associated with
      increases in brain formaldehyde levels. An ELISA assay revealed that the AVP
      injection increased both the protein level and the enzymatic activity of
      semicarbazide-sensitive amine oxidase (SSAO), which is an enzyme that produces
      formaldehyde. In contrast, the intraperitoneal injection of formaldehyde
      increased the serum AVP level by increasing the angiotensin II (ANG II) level,
      and this change was associated with a marked decrease in water intake behavior.
      These data suggest that the interaction between formaldehyde and AVP affects the
      water intake behaviors of mice. Furthermore, the highest concentration of
      formaldehyde in vivo was observed in the morning. Regular water intake is
      conducive to eliminating endogenous formaldehyde from the human body,
      particularly when water is consumed in the morning. Establishing good water
      intake habits not only effectively eliminates excess formaldehyde and other
      metabolic products but is also expected to yield valuable approaches to reducing
      the risk of AD prior to the onset of the disease.

PMID- 27699081
TI  - Fear of Falling Correlates with Subtle Neuromuscular Balance and Strength
      Deficits of Fragility Fracture Patients.
AB  - Fragility fractures, or fractures occurring from a low-trauma event, are
      extremely prevalent among the elderly population worldwide and associated with
      significant mortality and morbidity. This study evaluated the relationship
      between FES-I Fear of Falling Survey results, self-reported activity restrictions
      via the SF-36 survey, and scores recorded by portable, inexpensive clinical
      assessment tools (CATs) during dynamic functional tasks. Low scores during these
      tasks may indicate functional deficits that put patients at risk for falls and
      subsequent fragility fractures. Forty-one subjects (20 fragility fracture
      patients, 21 controls without history of fragility fractures) over the age of 50
      were recruited from three outpatient orthopaedic clinics. All subjects were
      administered a FES-I Fear of Falling Survey, a portion of an SF-36 survey, and
      tested using three different portable CATs: the Wii Balance Board, iPod Level
      Belt and Saehan Squeeze Hand Grip Dynamometer. There were several measured
      variables that showed a moderate correlation with Fear of Falling scores. Of
      note, correlations between FES-I scores and maximum hand grip strength for both
      the dominant hand (R= -0.302, p=0.069) and non-dominant hand (R= -0.309,
      p=0.059), as well as maximum anterior-posterior sway measured by the iPod Level
      Belt (R=0.320, p=0.056) were found to be marginally significant. In addition, the
      correlation between FES-I and average anterior-posterior sway was found to be
      significant (R=0.416, p=0.012). The Nintendo Wii and iPod Level Belt are
      relatively inexpensive, portable tools that can assess patients for subtle
      deficits during dynamic functional tasks. The results indicate that these tools
      can provide a more objective measure of a patient's limitations during daily
      activities such as walking by assigning them a numerical value and correlating
      this value to physical deficits that impact balance and coordination. In the
      future, CATs may also have a role in predicting outcomes and in individualizing
      care, therapy, and at-home preventive measures.

PMID- 27699082
TI  - Relevance Study on Cerebral Infarction and Resistin Gene Polymorphism in Chinese
      Han Population.
AB  - Recent research on genome-wide associations has implicated that the serum
      resistin level and its gene polymorphism are associated with cerebral infarction
      (CI) morbidity and prognosis, and could thereby regulate CI. This study aimed to
      investigate the association between the resistin single nucleotide polymorphism
      (SNP) and the susceptibility to CI in the Chinese Han population. A total of 550
      CI patients and 313 healthy controls were genotyped. Nine SNPs of the resistin
      gene previously shown were sequenced and assessed for an association with CI. The
      numbers of GG genotype carriers of rs3219175 and rs3486119 in the CI group were
      significantly higher than those in the control group among the middle-aged group
      (aged 45-65), at 76% vs 67.9% (P=0.025) and 75.5% vs 67.9% (P=0.031). rs3219175
      and rs34861192 were associated with CI in the dominant and superdominant models
      according to the genetic model analysis (P<0.05). Meanwhile, there was strong
      linkage disequilibrium among the rs34124816, rs3219175, rs34861192, rs1862513,
      rs3745367, 180C/G and rs3745369 sites. In a haplotype analysis, the occurrence
      rate of the haplotype AGGCAGC was 1.97 times (P<0.05) higher in the patient group
      than in the control group. In addition, the numbers of GG genotype carriers of
      rs3219175 and rs3486119 in the middle-aged male CI patients and the middle-aged
      small artery occlusion (SAO) CI patients were higher than those in the control
      group (P<0.05). In the Chinese Han middle-aged population, the GG gene type
      carriers of the resistin gene sites rs3219175 and rs34861192 had a high risk for
      CI onset, especially in middle-aged male patients and SAO CI in all middle-aged
      patients.

PMID- 27699083
TI  - Oxidative Stress-induced Telomere Length Shortening of Circulating Leukocyte in
      Patients with Obstructive Sleep Apnea.
AB  - The main mechanism of pathogenesis which causes systemic complications in
      obstructive sleep apnea (OSA) patients is believed to be intermittent hypoxia
      induced intermediary effect and it depends on the burden of oxidative stress
      during sleep. We aimed to search the predictive markers which reflect the burden
      of systemic oxidative stress in patients with OSA and whether excessive telomere
      length shortening is a characteristic feature that can assess oxidative stress
      levels. We used quantitative PCR to measure telomere length using peripheral
      blood genomic DNA. Telomere lengths were compared in an age- and body mass index
      (BMI)-dependent manner in 34 healthy volunteers and 43 OSA subjects. We also
      performed reactive oxygen species assay to measure the concentration of hydrogen
      peroxide in the peripheral blood of healthy volunteers and OSA subjects. We found
      that the serum concentration of hydrogen peroxide was considerably higher in OSA
      patients, and that this was closely related with the severity of OSA.
      Significantly shortened telomere length was observed in the circulating
      leukocytes of the peripheral blood of OSA patients, and telomere length
      shortening was aggravated more acutely in an age- and BMI-dependent manner. An
      inverse correlation was observed between the concentration of hydrogen peroxide
      and the telomere length of OSA patients and excessive telomere length shortening
      was also linked to severity of OSA. The results provided evidence that telomere
      length shortening or excessive cellular aging might be distinctive in circulating
      leukocyte of OSA patients and may be an predictive biomarker for reflect the
      burden of oxidative stress in the peripheral blood of OSA patients.

PMID- 27699084
TI  - Serum IL-33 Is a Novel Diagnostic and Prognostic Biomarker in Acute Ischemic
      Stroke.
AB  - Interleukin-33 (IL-33), a newly recognized IL-1 family member, is expressed in
      various tissues and cells, and involved in pathogenesis of many human diseases.
      For example, IL-33 plays a protective role in cardiovascular diseases. However,
      the role of IL-33 in acute ischemic stroke (AIS) remains unclear. This study aims
      to investigate whether IL-33 level in AIS patient serum can be used as a
      potential diagnostic and prognostic marker. The study included two hundred and
      six patients with first-ever ischemic stroke, who were admitted within 72 hours
      after stroke onset. The serum level of IL-33 was measured with ELISA and the
      severity of AIS patients on admission was evaluated based on the National
      Institutes of Health Stroke Scale (NIHSS) score. The functional outcome at 3
      months was determined using the Barthel index (BI). We found that serum IL-33 was
      significantly higher (P < 0.001) in patients with AIS [57.68 ng/L (IQR, 44.95
      76.73)] compared with healthy controls [47.48 ng/L (IQR, 38.67-53.78)]. IL-33 was
      an independent diagnostic biomarker for AIS with an OR of 1.051 (95%Cl, 1.018
      1.085; P=0.002). Serum IL-33 was higher (P < 0.05) in the stroke patients with
      small cerebral infarction volume compared to AIS patients with large cerebral
      infarction. In addition, serum IL-33 was also significantly higher (P = 0.001) in
      the patients with mild stroke, compared to the patients with severe stroke.
      Furthermore, serum IL-33 level in AIS patients with a worse outcome was higher (P
      < 0.001) compared to AIS patients with a better outcome. IL-33 was also an
      independent predictor for the functional outcome with an adjusted OR of 0.932
      (95% CI, 0.882-0.986). Our results suggest that the lower level of serum IL-33 is
      associated with large infarction volume and greater stroke severity in AIS
      patients. Thus, IL-33 can be used as a novel and independent diagnostic and
      predicting prognostic marker in AIS.

PMID- 27699085
TI  - Proteomic Analysis of the Peri-Infarct Area after Human Umbilical Cord
      Mesenchymal Stem Cell Transplantation in Experimental Stroke.
AB  - Among various therapeutic approaches for stroke, treatment with human umbilical
      cord mesenchymal stem cells (hUC-MSCs) has acquired some promising results.
      However, the underlying mechanisms remain unclear. We analyzed the protein
      expression spectrum of the cortical peri-infarction region after ischemic stroke
      followed by treatment with hUC-MSCs, and found 16 proteins expressed
      differentially between groups treated with or without hUC-MSCs. These proteins
      were further determined by Gene Ontology term analysis and network with CD200
      CD200R1, CCL21-CXCR3 and transcription factors. Three of them: Abca13, Grb2 and
      Ptgds were verified by qPCR and ELISA. We found the protein level of Abca13 and
      the mRNA level of Grb2 consistent with results from the proteomic analysis.
      Finally, the function of these proteins was described and the potential proteins
      that deserve to be further studied was also highlighted. Our data may provide
      possible underlying mechanisms for the treatment of stroke using hUC-MSCs.

PMID- 27699089
TI  - In vivo fluorescence imaging of hepatocellular carcinoma xenograft using near
      infrared labeled epidermal growth factor receptor (EGFR) peptide.
AB  - Minimally-invasive surgery of hepatocellular carcinoma (HCC) can be limited by
      poor tumor visualization with white light. We demonstrate systemic administration
      of a Cy5.5-labeled peptide specific for epidermal growth factor receptor (EGFR)
      to target HCC in vivo in a mouse xenograft model. We attached a compact imaging
      module to the proximal end of a medical laparoscope to collect near-infrared
      fluorescence and reflectance images concurrently at 15 frames/sec. We measured a
      mean target-to-background ratio of 2.99 +/- 0.22 from 13 surgically exposed
      subcutaneous human HCC tumors in vivo in 5 mice. This integrated imaging
      methodology is promising to guide laparoscopic resection of HCC.

PMID- 27699088
TI  - Efficient Benzimidazolidinone Synthesis via Rhodium-Catalyzed Double
      Decarbonylative C-C Activation/Cycloaddition between Isatins and Isocyanates.
AB  - The first decarbonylative cycloaddition of less-strained cyclic ketones (isatins)
      with isocyanates is reported. Initiated by C-C activation, this distinct [5-2+2]
      transformation provides a rapid entry to access various benzimidazolidinone
      derivatives, through which a wide range of isocyanates can be efficiently coupled
      with broad functional group tolerance. A modified one-pot process, combining
      Curtius rearrangement and C-C activation, was also achieved by using acyl azides
      as the starting materials. Detailed mechanistic study revealed a surprising
      double-decarbonylative reaction pathway. The novel reactivity discovered in this
      basic research is expected to shed light on developing new heterocycle formation
      methods through a C-C/isocyanate coupling.

PMID- 27699091
TI  - Multimodal optical coherence tomography and fluorescence lifetime imaging with
      interleaved excitation sources for simultaneous endogenous and exogenous
      fluorescence.
AB  - Multimodal imaging probes a variety of tissue properties in a single image
      acquisition by merging complimentary imaging technologies. Exploiting synergies
      amongst the data, algorithms can be developed that lead to better tissue
      characterization than could be accomplished by the constituent imaging modalities
      taken alone. The combination of optical coherence tomography (OCT) with
      fluorescence lifetime imaging microscopy (FLIM) provides access to detailed
      tissue morphology and local biochemistry. The optical system described here
      merges 1310 nm swept-source OCT with time-domain FLIM having excitation at 355
      and 532 nm. The pulses from 355 and 532 nm lasers have been interleaved to enable
      simultaneous acquisition of endogenous and exogenous fluorescence signals,
      respectively. The multimodal imaging system was validated using tissue phantoms.
      Nonspecific tagging with Alexa Flour 532 in a Watanbe rabbit aorta and active
      tagging of the LOX-1 receptor in human coronary artery, demonstrate the capacity
      of the system for simultaneous acquisition of OCT, endogenous FLIM, and exogenous
      FLIM in tissues.

PMID- 27699087
TI  - Guanosine: a Neuromodulator with Therapeutic Potential in Brain Disorders.
AB  - Guanosine is a purine nucleoside with important functions in cell metabolism and
      a protective role in response to degenerative diseases or injury. The past decade
      has seen major advances in identifying the modulatory role of extracellular
      action of guanosine in the central nervous system (CNS). Evidence from rodent and
      cell models show a number of neurotrophic and neuroprotective effects of
      guanosine preventing deleterious consequences of seizures, spinal cord injury,
      pain, mood disorders and aging-related diseases, such as ischemia, Parkinson's
      and Alzheimer's diseases. The present review describes the findings of in vivo
      and in vitro studies and offers an update of guanosine effects in the CNS. We
      address the protein targets for guanosine action and its interaction with
      glutamatergic and adenosinergic systems and with calcium-activated potassium
      channels. We also discuss the intracellular mechanisms modulated by guanosine
      preventing oxidative damage, mitochondrial dysfunction, inflammatory burden and
      modulation of glutamate transport. New and exciting avenues for future
      investigation into the protective effects of guanosine include characterization
      of a selective guanosine receptor. A better understanding of the neuromodulatory
      action of guanosine will allow the development of therapeutic approach to brain
      diseases.

PMID- 27699090
TI  - Visualization of prostatic nerves by polarization-sensitive optical coherence
      tomography.
AB  - Preservation of prostatic nerves is critical to recovery of a man's sexual
      potency after radical prostatectomy. A real-time imaging method of prostatic
      nerves will be helpful for nerve-sparing radical prostatectomy (NSRP).
      Polarization-sensitive optical coherence tomography (PS-OCT), which provides both
      structural and birefringent information of tissue, was applied for detection of
      prostatic nerves in both rat and human prostate specimens, ex vivo. PS-OCT
      imaging of rat prostate specimens visualized highly scattering and birefringent
      fibrous structures superficially, and these birefringent structures were
      confirmed to be nerves by histology or multiphoton microscopy (MPM). PS-OCT could
      easily distinguish these birefringent structures from surrounding other tissue
      compartments such as prostatic glands and fats. PS-OCT imaging of human
      prostatectomy specimens visualized two different birefringent structures,
      appearing fibrous and sheet-like. The fibrous ones were confirmed to be nerves by
      histology, and the sheet-like ones were considered to be fascias surrounding the
      human prostate. PS-OCT imaging of human prostatectomy specimens along the
      perimeter showed spatial variation in the amount of birefringent fibrous
      structures which was consistent with anatomy. These results demonstrate the
      feasibility of PS-OCT for detection of prostatic nerves, and this study will
      provide a basis for intraoperative use of PS-OCT.

PMID- 27699092
TI  - Combination of confocal principle and aperture stop separation improves
      suppression of crystalline lens fluorescence in an eye model.
AB  - Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a new technique to detect
      changes in the human retina. The autofluorescence decay over time, generated by
      endogenous fluorophores, is measured in vivo. The strong autofluorescence of the
      crystalline lens, however, superimposes the intensity decay of the retina
      fluorescence, as the confocal principle is not able to suppress it sufficiently.
      Thus, the crystalline lens autofluorescence causes artifacts in the retinal
      fluorescence lifetimes determined from the intensity decays. Here, we present a
      new technique to suppress the autofluorescence of the crystalline lens by
      introducing an annular stop into the detection light path, which we call
      Schweitzer's principle. The efficacy of annular stops with an outer diameter of 7
      mm and inner diameters of 1 to 5 mm are analyzed in an experimental setup using a
      model eye based on fluorescent dyes. Compared to the confocal principle,
      Schweitzer's principle with an inner diameter of 3 mm is able to reduce the
      simulated crystalline lens fluorescence to 4%, while 42% of the simulated retina
      fluorescence is preserved. Thus, we recommend the implementation of Schweitzer's
      principle in scanning laser ophthalmoscopes used for fundus autofluorescence
      measurements, especially the FLIO device, for improved image quality.

PMID- 27699093
TI  - In vitro neuronal depolarization and increased synaptic activity induced by
      infrared neural stimulation.
AB  - Neuronal responses to infrared neural stimulation (INS) are explored at the
      single cell level using patch-clamp electrophysiology. We examined membrane and
      synaptic responses of solitary tract neurons recorded in acute slices prepared
      from the Sprague-Dawley rat. Neurons were stimulated using a compact 1890 nm
      waveguide laser with light delivered to a small target area, comparable to the
      size of a single cell, via a single-mode fiber. We show that infrared radiation
      increased spontaneous synaptic event frequency, and evoked steady-state currents
      and neuronal depolarization. The magnitude of the responses was proportional to
      laser output.

PMID- 27699094
TI  - Visible-light optical coherence tomography-based multimodal retinal imaging for
      improvement of fluorescent intensity quantification.
AB  - We developed a spectral-domain visible-light optical coherence tomography (VIS
      OCT) based multimodal imaging technique which can accomplish simultaneous OCT and
      fluorescence imaging with a single broadband light source. Phantom experiments
      showed that by using the simultaneously acquired OCT images as a reference, the
      effect of light attenuation on the intensity of the fluorescent images by
      materials in front of the fluorescent target can be compensated. This capability
      of the multimodal imaging technique is of high importance for achieving
      quantification of the true intensities of autofluorescence (AF) imaging of the
      retina. We applied the technique in retinal imaging including AF imaging of the
      retinal pigment epithelium and fluorescein angiography (FA). We successfully
      demonstrated the effect of compensation on AF and FA images with the
      simultaneously acquired VIS-OCT images.

PMID- 27699095
TI  - Photonic sensing of arterial distension.
AB  - Most cardiovascular diseases, such as arteriosclerosis and hypertension, are
      directly linked to pathological changes in hemodynamics, i.e. the complex
      coupling of blood pressure, blood flow and arterial distension. To improve the
      current understanding of cardiovascular diseases and pave the way for novel
      cardiovascular diagnostics, innovative tools are required that measure pressure,
      flow, and distension waveforms with yet unattained spatiotemporal resolution. In
      this context, miniaturized implantable solutions for continuously measuring these
      parameters over the long-term are of particular interest. We present here an
      implantable photonic sensor system capable of sensing arterial wall movements of
      a few hundred microns in vivo with sub-micron resolution, a precision in the
      micrometer range and a temporal resolution of 10 kHz. The photonic measurement
      principle is based on transmission photoplethysmography with stretchable
      optoelectronic sensors applied directly to large systemic arteries. The presented
      photonic sensor system expands the toolbox of cardiovascular measurement
      techniques and makes these key vital parameters continuously accessible over the
      long-term. In the near term, this new approach offers a tool for clinical
      research, and as a perspective, a continuous long-term monitoring system that
      enables novel diagnostic methods in arteriosclerosis and hypertension research
      that follow the trend in quantifying cardiovascular diseases by measuring
      arterial stiffness and more generally analyzing pulse contours.

PMID- 27699086
TI  - Atrial Fibrillation: The Science behind Its Defiance.
AB  - Atrial fibrillation (AF) is the most prevalent arrhythmia in the world, due both
      to its tenacious treatment resistance, and to the tremendous number of risk
      factors that set the stage for the atria to fibrillate. Cardiopulmonary,
      behavioral, and psychological risk factors generate electrical and structural
      alterations of the atria that promote reentry and wavebreak. These culminate in
      fibrillation once atrial ectopic beats set the arrhythmia process in motion.
      There is growing evidence that chronic stress can physically alter the emotion
      centers of the limbic system, changing their input to the hypothalamic-limbic
      autonomic network that regulates autonomic outflow. This leads to imbalance of
      the parasympathetic and sympathetic nervous systems, most often in favor of
      sympathetic overactivation. Autonomic imbalance acts as a driving force behind
      the atrial ectopy and reentry that promote AF. Careful study of AF
      pathophysiology can illuminate the means that enable AF to elude both
      pharmacological control and surgical cure, by revealing ways in which
      antiarrhythmic drugs and surgical and ablation procedures may paradoxically
      promote fibrillation. Understanding AF pathophysiology can also help clarify the
      mechanisms by which emerging modalities aiming to correct autonomic imbalance,
      such as renal sympathetic denervation, may offer potential to better control this
      arrhythmia. Finally, growing evidence supports lifestyle modification approaches
      as adjuncts to improve AF control.

PMID- 27699096
TI  - Dark field optical imaging reveals vascular changes in an inducible hamster cheek
      pouch model during carcinogenesis.
AB  - In this study, we propose a low-cost cross-polarized dark field microscopy system
      for in vivo vascular imaging to detect head and neck cancer. A simple-to-use
      Gabor-filter-based image processing technique was developed to objectively and
      automatically quantify several important vascular features, including tortuosity,
      length, diameter and area fraction, from vascular images. Simulations were
      performed to evaluate the accuracies of vessel segmentation and feature
      extraction for our algorithm. Sensitivity and specificity for vessel segmentation
      of the Gabor masks both remained above 80% at all contrast levels when compared
      to gold-standard masks. Errors for vascular feature extraction were under 5%.
      Moreover, vascular contrast and vessel diameter were identified to be the two
      primary factors which affected the segmentation accuracies. After our algorithm
      was validated, we monitored the blood vessels in an inducible hamster cheek pouch
      carcinogen model over 17 weeks and quantified vascular features during
      carcinogenesis. A significant increase in vascular tortuosity and a significant
      decrease in vessel length were observed during carcinogenesis.

PMID- 27699098
TI  - Microdose fluorescence imaging of ABY-029 on an operating microscope adapted by
      custom illumination and imaging modules.
AB  - Fluorescence guided surgery has the potential to positively impact surgical
      oncology; current operating microscopes and stand-alone imaging systems are too
      insensitive or too cumbersome to maximally take advantage of new tumor-specific
      agents developed through the microdose pathway. To this end, a custom-built
      illumination and imaging module enabling picomolar-sensitive near-infrared
      fluorescence imaging on a commercial operating microscope is described. The
      limits of detection and system specifications are characterized, and in vivo
      efficacy of the system in detecting ABY-029 is evaluated in a rat orthotopic
      glioma model following microdose injections, showing the suitability of the
      device for microdose phase 0 clinical trials.

PMID- 27699097
TI  - Non-invasive diffuse correlation tomography reveals spatial and temporal blood
      flow differences in murine bone grafting approaches.
AB  - Longitudinal blood flow during murine bone graft healing was monitored non
      invasively using diffuse correlation tomography. The system utilized spatially
      dense data from a scanning set-up, non-linear reconstruction, and micro-CT
      anatomical information. Weekly in vivo measurements were performed. Blood flow
      changes in autografts, which heal successfully, were localized to graft regions
      and consistent across mice. Poor healing allografts showed heterogeneous blood
      flow elevation and high inter-subject variabilities. Allografts with tissue
      engineered periosteum showed responses intermediate to both autografts and
      allografts, consistent with healing observed. These findings suggest that
      spatiotemporal blood flow changes can be utilized to differentiate the degree of
      bone graft healing.

PMID- 27699099
TI  - Optofluidic chips with nanochannels for dynamic molecular detection using
      enhanced fluorescence.
AB  - The fabrication of a novel optofluidic chip using nanochannels optimized for DNA
      stretched molecules and optical detection by enhanced fluorescence is reported.
      The chips are composed of a series of microchannels that allow the transport of
      molecules in the femto-liter per second inside a fluid or gas. The nanochannels
      are surrounded by a photonic crystal structure to enhance the emission of
      fluorescent light from the molecules, which can travel along the nanochannel,
      allowing for enhanced optical detection of the molecules in motion. The photonic
      crystal structure provides an enhancement up to 2.5 times in the light emitted
      from fluorescent molecules inside the nanochannels which increases to around 250
      when normalized to the area of the nanochannels emitting fluorescence. The
      results may help to the detection of fluorescent molecules (like marked-DNA) in
      series by speeding it and allowing the use of less sophisticated equipment.

PMID- 27699100
TI  - Structure-adaptive CBCT reconstruction using weighted total variation and Hessian
      penalties.
AB  - The exposure of normal tissues to high radiation during cone-beam CT (CBCT)
      imaging increases the risk of cancer and genetic defects. Statistical iterative
      algorithms with the total variation (TV) penalty have been widely used for low
      dose CBCT reconstruction, with state-of-the-art performance in suppressing noise
      and preserving edges. However, TV is a first-order penalty and sometimes leads to
      the so-called staircase effect, particularly over regions with smooth intensity
      transition in the reconstruction images. A second-order penalty known as the
      Hessian penalty was recently used to replace TV to suppress the staircase effect
      in CBCT reconstruction at the cost of slightly blurring object edges. In this
      study, we proposed a new penalty, the TV-H, which combines TV and Hessian
      penalties for CBCT reconstruction in a structure-adaptive way. The TV-H penalty
      automatically differentiates the edges, gradual transition and uniform local
      regions within an image using the voxel gradient, and adaptively weights TV and
      Hessian according to the local image structures in the reconstruction process.
      Our proposed penalty retains the benefits of TV, including noise suppression and
      edge preservation. It also maintains the structures in regions with gradual
      intensity transition more successfully. A majorization-minimization (MM) approach
      was designed to optimize the objective energy function constructed with the TV-H
      penalty. The MM approach employed a quadratic upper bound of the original
      objective function, and the original optimization problem was changed to a series
      of quadratic optimization problems, which could be efficiently solved using the
      Gauss-Seidel update strategy. We tested the reconstruction algorithm on two
      simulated digital phantoms and two physical phantoms. Our experiments indicated
      that the TV-H penalty visually and quantitatively outperformed both TV and
      Hessian penalties.

PMID- 27699101
TI  - Multi-spectral photoacoustic elasticity tomography.
AB  - The goal of this work was to develop and validate a spectrally resolved
      photoacoustic imaging method, namely multi-spectral photoacoustic elasticity
      tomography (PAET) for quantifying the physiological parameters and elastic
      modulus of biological tissues. We theoretically and experimentally examined the
      PAET imaging method using simulations and in vitro experimental tests. Our
      simulation and in vitro experimental results indicated that the reconstructions
      were quantitatively accurate in terms of sizes, the physiological and elastic
      properties of the targets.

PMID- 27699102
TI  - Supercontinuum as a light source for miniaturized endoscopes.
AB  - In this work, we have successfully implemented supercontinuum based illumination
      through single fiber coupling. The integration of a single fiber illumination
      with a miniature CMOS sensor forms a very slim and powerful camera module for
      endoscopic imaging. A set of tests and in vivo animal experiments are conducted
      accordingly to characterize the corresponding illuminance, spectral profile,
      intensity distribution, and image quality. The key illumination parameters of the
      supercontinuum, including color rendering index (CRI: 72%~97%) and correlated
      color temperature (CCT: 3,100K~5,200K), are modified with external filters and
      compared with those from a LED light source (CRI~76% & CCT~6,500K). The very high
      spatial coherence of the supercontinuum allows high luminosity conduction through
      a single multimode fiber (core size~400MUm), whose distal end tip is attached
      with a diffussion tip to broaden the solid angle of illumination (from less than
      10 degrees  to more than 80 degrees ).

PMID- 27699103
TI  - Optical coherence tomography endoscopic probe based on a tilted MEMS mirror.
AB  - This paper reports a compact microendoscopic OCT probe with an outer diameter of
      only 2.7 mm. The small diameter is enabled by a novel 2-axis scanning MEMS mirror
      with a preset 45 degrees  tilted angle. The tilted MEMS mirror is directly
      integrated on a silicon optical bench (SiOB). The SiOB provides mechanical
      support and electrical wiring to the mirror plate via a set of bimorph flexure,
      enabling a compact probe mount design without the requirement of a 45 degrees 
      slope, which is capable to dramatically reduce the probe size and ease the
      assembly process. Additionally, the SiOB also provides trenches with properly
      designed opening widths for automatic alignment of the MEMS mirror, GRIN lens and
      optical fiber. The 45 degrees -tilted MEMS mirror plate is actuated by four
      electrothermal bimorph actuators. The packaged 2.7 mm-diameter probe offers 2
      axis side-view optical scanning with a large optical scan range of 40 degrees  at
      a low drive voltage of 5.5 Vdc in both axes, allowing a lateral scan area of 2.2
      mm * 2.2 mm at a 3 mm working distance. High-resolution 2D and 3D OCT images of
      the IR card, ex vivo imaging of meniscus specimens and rat brain slices, in vivo
      imaging of the human finger and nail have been obtained with a TDOCT system.

PMID- 27699104
TI  - Tracking single fluorescent particles in three dimensions via extremum seeking.
AB  - The ability to track single fluorescent particles in three-dimensions with sub
      diffraction limit precision as well as sub-millisecond temporal resolution has
      enabled the understanding of many biophysical phenomena at the nanometer scale.
      While there are several techniques for achieving this, most require complicated
      experimental setups that are expensive to implement. These methods can offer
      superb performance but their complexity may be overwhelming to the end-user whose
      aim is only to understand the feature being imaged. In this work, we describe a
      method for tracking a single fluorescent particle using a standard confocal or
      multi-photon microscope configuration. It relies only on the assumption that the
      relative position of the measurement point and the particle can be actuated and
      that the point spread function has a global maximum that coincides with the
      particle's position. The method uses intensity feedback to calculate real-time
      position commands that "seek" the extremum of the point spread function as the
      particle moves through its environment. We demonstrate the method by tracking a
      diffusing quantum dot in a hydrogel on a standard epifluorescent confocal
      microscope.

PMID- 27699105
TI  - Imaging hemodynamic response after ischemic stroke in mouse cortex using visible
      light optical coherence tomography.
AB  - Visible-light optical coherence tomography (Vis-OCT) is an emerging technology
      that can image hemodynamic response in microvasculature. Vis-OCT can retrieve
      blood oxygen saturation (sO2) mapping using intrinsic optical absorption contrast
      while providing high-resolution anatomical vascular structures at the same time.
      To improve the accuracy of Vis-OCT oximetry on vessels embedded in highly
      scattering medium, i.e., brain cortex, we developed and formulated a novel dual
      depth sampling and normalization strategy that allowed us to minimize the
      detrimental effect of ubiquitous tissue scattering. We applied our newly
      developed approach to monitor the hemodynamic response in mouse cortex after
      focal photothrombosis. We observed vessel dilatation, which was negatively
      correlated with the original vessel diameter, in the penumbra region. The sO2 of
      vessels in the penumbra region also dropped below normal range after focal
      ischemia.

PMID- 27699107
TI  - Dual-modality endomicroscopy with co-registered fluorescence and phase contrast.
AB  - We describe a dual-modality laser scanning endomicroscope that provides
      simultaneous fluorescence contrast based on confocal laser endomicroscopy (CLE)
      and phase-gradient contrast based on scanning oblique back-scattering microscopy
      (sOBM). The probe consists of a 2.6mm-diameter micro-objective attached to a
      30,000-core flexible fiber bundle. The dual contrasts are inherently co
      registered, providing complementary information on labeled and un-labeled sample
      structure. Proof of principle demonstrations are presented with ex-vivo mouse
      colon tissue.

PMID- 27699106
TI  - Combined multi-modal photoacoustic tomography, optical coherence tomography (OCT)
      and OCT angiography system with an articulated probe for in vivo human skin
      structure and vasculature imaging.
AB  - Cutaneous blood flow accounts for approximately 5% of cardiac output in human and
      plays a key role in a number of a physiological and pathological processes. We
      show for the first time a multi-modal photoacoustic tomography (PAT), optical
      coherence tomography (OCT) and OCT angiography system with an articulated probe
      to extract human cutaneous vasculature in vivo in various skin regions. OCT
      angiography supplements the microvasculature which PAT alone is unable to
      provide. Co-registered volumes for vessel network is further embedded in the
      morphologic image provided by OCT. This multi-modal system is therefore
      demonstrated as a valuable tool for comprehensive non-invasive human skin
      vasculature and morphology imaging in vivo.

PMID- 27699108
TI  - Algorithms for differentiating between images of heterogeneous tissue across
      fluorescence microscopes.
AB  - Fluorescence microscopy can be used to acquire real-time images of tissue
      morphology and with appropriate algorithms can rapidly quantify features
      associated with disease. The objective of this study was to assess the ability of
      various segmentation algorithms to isolate fluorescent positive features (FPFs)
      in heterogeneous images and identify an approach that can be used across multiple
      fluorescence microscopes with minimal tuning between systems. Specifically, we
      show a variety of image segmentation algorithms applied to images of stained
      tumor and muscle tissue acquired with 3 different fluorescence microscopes.
      Results indicate that a technique called maximally stable extremal regions
      followed by thresholding (MSER + Binary) yielded the greatest contrast in FPF
      density between tumor and muscle images across multiple microscopy systems.

PMID- 27699109
TI  - Design of a fiber-optic multiphoton microscopy handheld probe.
AB  - We have developed a fiber-optic multiphoton microscopy (MPM) system with handheld
      probe using femtosecond fiber laser. Here we present the detailed optical design
      and analysis of the handheld probe. The optical systems using Lightpath 352140
      and 352150 as objective lens were analyzed. A custom objective module that
      includes Lightpath 355392 and two customized corrective lenses was designed.
      Their performances were compared by wavefront error, field curvature,
      astigmatism, F-theta error, and tolerance in Zemax simulation. Tolerance analysis
      predicted the focal spot size to be 1.13, 1.19 and 0.83 um, respectively.
      Lightpath 352140 and 352150 were implemented in experiment and the measured
      lateral resolution was 1.22 and 1.3 um, respectively, which matched with the
      prediction. MPM imaging by the handheld probe were conducted on leaf, fish scale
      and rat tail tendon. The MPM resolution can potentially be improved by the custom
      objective module.

PMID- 27699110
TI  - Single cell ionization by a laser trap: a preliminary study in measuring
      radiation dose and charge in BT20 breast carcinoma cells.
AB  - In this work, a preliminary study in the application of a laser trap for
      ionization of living carcinoma cells is presented. The study was conducted using
      BT20 breast carcinoma cells cultured and harvested in our laboratory. Each cell,
      for a total of 50 cells, was trapped and ionized by a high intensity infrared
      laser at 1064 nm. The threshold radiation dose and the resultant charge from the
      ionization for each cell were determined. With the laser trap serving as a
      radiation source, the cell underwent dielectric breakdown of the membrane. When
      this process occurs, the cell becomes highly charged and its dielectric
      susceptibility changes. The charge creates an increasing electrostatic force
      while the changing dielectric susceptibility diminishes the strength of the
      trapping force. Consequently, at some instant of time the cell gets ejected from
      the trap. The time inside the trap while the cell is being ionized, the intensity
      of the radiation, and the post ionization trajectory of the cell were used to
      determine the threshold radiation dose and the charge for each cell. The
      measurement of the charge vs ionization radiation dose at single cell level could
      be useful in the accuracy of radiotherapy as the individual charges can
      collectively create a strong enough electrical interaction to cause dielectric
      breakdown in other cells in a tumor.

PMID- 27699111
TI  - Multiphoton excited hemoglobin fluorescence and third harmonic generation for non
      invasive microscopy of stored blood.
AB  - Red blood cells (RBC) in two-photon excited fluorescence (TPEF) microscopy
      usually appear as dark disks because of their low fluorescent signal. Here we use
      15fs 800nm pulses for TPEF, 45fs 1060nm pulses for three-photon excited
      fluorescence, and third harmonic generation (THG) imaging. We find sufficient
      fluorescent signal that we attribute to hemoglobin fluorescence after comparing
      time and wavelength resolved spectra of other expected RBC endogenous
      fluorophores: NADH, FAD, biliverdin, and bilirubin. We find that both TPEF and
      THG microscopy can be used to examine erythrocyte morphology non-invasively
      without breaching a blood storage bag.

PMID- 27699112
TI  - Continuous cerebral hemodynamic measurement during deep hypothermic circulatory
      arrest.
AB  - While survival of children with complex congenital heart defects has improved in
      recent years, roughly half suffer neurological deficits suspected to be related
      to cerebral ischemia. Here we report the first demonstration of optical diffuse
      correlation spectroscopy (DCS) for continuous and non-invasive monitoring of
      cerebral microvascular blood flow during complex human neonatal or cardiac
      surgery. Comparison between DCS and Doppler ultrasound flow measurements during
      deep hypothermia, circulatory arrest, and rewarming were in good agreement.
      Looking forward, DCS instrumentation, alone and with NIRS, could provide access
      to flow and metabolic biomarkers needed by clinicians to adjust neuroprotective
      therapy during surgery.

PMID- 27699113
TI  - Minimum change in spherical aberration that can be perceived.
AB  - It is important to know the visual sensitivity to optical blur from both a basic
      science perspective and a practical point of view. Of particular interest is the
      sensitivity to blur induced by spherical aberration because it is being used to
      increase depth of focus as a component of a presbyopic solution. Using a flicker
      detection-based procedure implemented on an adaptive optics visual simulator, we
      measured the spherical aberration thresholds that produce just-noticeable
      differences in perceived image quality. The thresholds were measured for positive
      and negative values of spherical aberration, for best focus and + 0.5 D and + 1.0
      D of defocus. At best focus, the SA thresholds were 0.20 +/- 0.01 um and -0.17 +/
      0.03 um for positive and negative spherical aberration respectively (referred to
      a 6-mm pupil). These experimental values may be useful in setting spherical
      aberration permissible levels in different ophthalmic techniques.

PMID- 27699114
TI  - Automated, highly reproducible, wide-field, light-based cortical mapping method
      using a commercial stereo microscope and its applications.
AB  - We introduce a more flexible optogenetics-based mapping system attached on a
      stereo microscope, which offers automatic light stimulation to individual regions
      of interest in the cortex that expresses light-activated channelrhodopsin-2 in
      vivo. Combining simultaneous recording of electromyography from specific forelimb
      muscles, we demonstrate that this system offers much better efficiency and
      precision in mapping distinct domains for controlling limb muscles in the mouse
      motor cortex. Furthermore, the compact and modular design of the system also
      yields a simple and flexible implementation to different commercial stereo
      microscopes, and thus could be widely used among laboratories.

PMID- 27699115
TI  - Bundled-optode implementation for 3D imaging in functional near-infrared
      spectroscopy.
AB  - The paper presents a functional near-infrared spectroscopy (fNIRS)-based bundled
      optode method for detection of the changes of oxy-hemoglobin (HbO) and deoxy
      hemoglobin (HbR) concentrations. fNIRS with 32 optodes is utilized to measure
      five healthy male subjects' brain-hemodynamic responses to arithmetic tasks.
      Specifically, the coordinates of 256 voxels in the three-dimensional (3D) volume
      are computed according to the known probe geometry. The mean path length factor
      in the Beer-Lambert equation is estimated as a function of the emitter-detector
      distance, which is utilized for computation of the absorption coefficient. The
      mean values of HbO and HbR obtained from the absorption coefficient are then
      applied for construction of a 3D fNIRS image. Our results show that the proposed
      method, as compared with the conventional approach, can detect brain activity
      with higher spatial resolution. This method can be extended for 3D fNIRS imaging
      in real-time applications.

PMID- 27699116
TI  - Measurement of biofilm growth and local hydrodynamics using optical coherence
      tomography.
AB  - We report on localized and simultaneous measurement of biofilm growth and local
      hydrodynamics in a microfluidic channel using optical coherence tomography. We
      measure independently with high spatio-temporal resolution the longitudinal flow
      velocity component parallel to the imaging beam and the transverse flow velocity
      component perpendicular to the imaging beam. Based on the measured velocities we
      calculate the shear-rates in the flow channel. We show the relation between the
      measured biofilm structure and flow velocities as biofilm growth progresses over
      the course of 48 hours.

PMID- 27699117
TI  - Characterizing fibrosis in UUO mice model using multiparametric analysis of
      phasor distribution from FLIM images.
AB  - Phasor approach to fluorescence lifetime microscopy is used to study development
      of fibrosis in the unilateral ureteral obstruction model (UUO) of kidney in mice.
      Traditional phasor analysis has been modified to create a multiparametric
      analysis scheme that splits the phasor points in four equidistance segments based
      on the height of peak of the phasor distribution and calculates six parameters
      including average phasor positions, the shape of each segment, the angle of the
      distribution and the number of points in each segment. These parameters are used
      to create a spectrum of twenty four points specific to the phasor distribution of
      each sample. Comparisons of spectra from diseased and healthy tissues result in
      quantitative separation and calculation of statistical parameters including AUC
      values, positive prediction values and sensitivity. This is a new method in the
      evolving field of analyzing phasor distribution of FLIM data and provides further
      insights. Additionally, the progression of fibrosis with time is detected using
      this multiparametric approach to phasor analysis.

PMID- 27699118
TI  - Handheld nonlinear microscope system comprising a 2 MHz repetition rate, mode
      locked Yb-fiber laser for in vivo biomedical imaging.
AB  - A novel, Yb-fiber laser based, handheld 2PEF/SHG microscope imaging system is
      introduced. It is suitable for in vivo imaging of murine skin at an average power
      level as low as 5 mW at 200 kHz sampling rate. Amplified and compressed laser
      pulses having a spectral bandwidth of 8 to 12 nm at around 1030 nm excite the
      biological samples at a ~1.89 MHz repetition rate, which explains how the high
      quality two-photon excitation fluorescence (2PEF) and second harmonic generation
      (SHG) images are obtained at the average power level of a laser pointer. The
      scanning, imaging and detection head, which comprises a conventional microscope
      objective for beam focusing, has a physical length of ~180 mm owing to the custom
      designed imaging telescope system between the laser scanner mirrors and the
      entrance aperture of the microscope objective. Operation of the all-fiber, all
      normal dispersion Yb-fiber ring laser oscillator is electronically controlled by
      a two-channel polarization controller for Q-switching free mode-locked operation.
      The whole nonlinear microscope imaging system has the main advantages of the low
      price of the fs laser applied, fiber optics flexibility, a relatively small,
      light-weight scanning and detection head, and a very low risk of thermal or
      photochemical damage of the skin samples.

PMID- 27699119
TI  - Whole-body multispectral photoacoustic imaging of adult zebrafish.
AB  - The zebrafish, an ideal vertebrate for studying developmental biology and
      genetics, is increasingly being used to understand human diseases, due to its
      high similarity to the human genome and its optical transparency during embryonic
      stages. Once the zebrafish has fully developed, especially wild-type breeds,
      conventional optical imaging techniques have difficulty in imaging the internal
      organs and structures with sufficient resolution and penetration depth. Even with
      established mutant lines that remain transparent throughout their life cycle, it
      is still challenging for purely optical imaging modalities to visualize the
      organs of juvenile and adult zebrafish at a micro-scale spatial resolution. In
      this work, we developed a non-invasive three-dimensional photoacoustic imaging
      platform with an optimized illumination pattern and a cylindrical-scanning-based
      data collection system to image entire zebrafish with micro-scale resolutions of
      80 MUm and 600 MUm in the lateral and axial directions, respectively. In
      addition, we employed a multispectral strategy that utilized excitation
      wavelengths from 690 nm to 930 nm to statistically quantify the relative optical
      absorption spectrum of major organs.

PMID- 27699120
TI  - Estimation of Jones matrix, birefringence and entropy using Cloude-Pottier
      decomposition in polarization-sensitive optical coherence tomography.
AB  - Estimation of polarimetric parameters has been a fundamental issue to assess
      biological tissues that have form birefringence or polarization scrambling in
      polarization-sensitive optical coherence tomography (PS-OCT). We present a
      mathematical framework to provide a maximum likelihood estimation of the target
      covariance matrix and its incoherent target decomposition to estimate a Jones
      matrix of a dominant scattering mechanism, called Cloude-Pottier decomposition,
      thereby deriving the phase retardation and the optic axis of the sample. In
      addition, we introduce entropy that shows the randomness of the polarization
      property. Underestimation of the entropy at a low sampling number is mitigated by
      asymptotic quasi maximum likelihood estimator. A bias of the entropy from random
      noises is corrected to show only the polarization property inherent in the
      sample. The theory is validated with experimental measurements of a glass plate
      and waveplates, and applied to the imaging of a healthy human eye anterior
      segment as an image filter.

PMID- 27699121
TI  - Direct visualization of functional heterogeneity in hepatobiliary metabolism
      using 6-CFDA as model compound.
AB  - Hepatobiliary metabolism is one of the major functions of the liver. However,
      little is known of the relationship between the physiological location of the
      hepatocytes and their metabolic potential. By the combination of time-lapse
      multiphoton microscopy and first order kinetic constant image analysis, the
      hepatocellular metabolic rate of the model compound 6-carboxyfluorescein
      diacetate (6-CFDA) is quantified at the single cell level. We found that the
      mouse liver can be divided into three zones, each with distinct metabolic rate
      constants. The sinusoidal uptake coefficients k1 of Zones 1, 2, and 3 are
      respectively 0.239 +/- 0.077, 0.295 +/- 0.087, and 0.338 +/- 0.133 min-1, the
      apical excreting coefficients k2 of Zones 1, 2, and 3 are 0.0117 +/- 0.0052,
      0.0175 +/- 0.0052, and 0.0332 +/- 0.0195 min-1, respectively. Our results show
      not only the existence of heterogeneities in hepatobiliary metabolism, but they
      also show that Zone 3 is the main area of metabolism.

PMID- 27699122
TI  - Multi-parameter analysis using photovoltaic cell-based optofluidic cytometer.
AB  - A multi-parameter optofluidic cytometer based on two low-cost commercial
      photovoltaic cells and an avalanche photodetector is proposed. The optofluidic
      cytometer is fabricated on a polydimethylsiloxane (PDMS) substrate and is capable
      of detecting side scattered (SSC), extinction (EXT) and fluorescence (FL) signals
      simultaneously using a free-space light transmission technique without the need
      for on-chip optical waveguides. The feasibility of the proposed device is
      demonstrated by detecting fluorescent-labeled polystyrene beads with sizes of 3
      MUm, 5 MUm and 10 MUm, respectively, and label-free beads with a size of 7.26
      MUm. The detection experiments are performed using both single-bead population
      samples and mixed-bead population samples. The detection results obtained using
      the SSC/EXT, EXT/FL and SSC/FL signals are compared with those obtained using a
      commercial flow cytometer. It is shown that the optofluidic cytometer achieves a
      high detection accuracy for both single-bead population samples and mixed-bead
      population samples. Consequently, the proposed device provides a versatile,
      straightforward and low-cost solution for a wide variety of point-of-care (PoC)
      cytometry applications.

PMID- 27699123
TI  - Imaging brain activity during seizures in freely behaving rats using a miniature
      multi-modal imaging system.
AB  - We report on a miniature label-free imaging system for monitoring brain blood
      flow and blood oxygenation changes in awake, freely behaving rats. The device,
      weighing 15 grams, enables imaging in a ~ 2 * 2 mm field of view with 4.4 MUm
      lateral resolution and 1 - 8 Hz temporal sampling rate. The imaging is performed
      through a chronically-implanted cranial window that remains optically clear
      between 2 to > 6 weeks after the craniotomy. This imaging method is well suited
      for longitudinal studies of chronic models of brain diseases and disorders. In
      this work, it is applied to monitoring neurovascular coupling during drug-induced
      absence-like seizures 6 weeks following the craniotomy.

PMID- 27699125
TI  - High-resolution real-time dual-view imaging with multiple point of view
      microscopy.
AB  - Most methods to observe three-dimensional processes in living samples are based
      on imaging a single plane that is sequentially scanned through the sample.
      Sequential scanning is inherently slow, which can make it difficult to capture
      objects moving quickly in three dimensions. Here we present a novel method,
      multiple point-of-view microscopy (MPoVM), that allows simultaneous capturing of
      the front and side views of a sample with high resolution. MPoVM can be
      implemented in most fluorescence microscopes, offering new opportunities in the
      study of dynamic biological processes in three dimensions.

PMID- 27699124
TI  - Chemotherapeutic drug-specific alteration of microvascular blood flow in murine
      breast cancer as measured by diffuse correlation spectroscopy.
AB  - The non-invasive, in vivo measurement of microvascular blood flow has the
      potential to enhance breast cancer therapy monitoring. Here, longitudinal blood
      flow of 4T1 murine breast cancer (N=125) under chemotherapy was quantified with
      diffuse correlation spectroscopy based on layer models. Six different treatment
      regimens involving doxorubicin, cyclophosphamide, and paclitaxel at clinically
      relevant doses were investigated. Treatments with cyclophosphamide increased
      blood flow as early as 3 days after administration, whereas paclitaxel induced a
      transient blood flow decrease at 1 day after administration. Early blood flow
      changes correlated strongly with the treatment outcome and distinguished treated
      from untreated mice individually for effective treatments.

PMID- 27699126
TI  - Preclinical photoacoustic models: application for ultrasensitive single cell
      malaria diagnosis in large vein and artery.
AB  - In vivo photoacoustic flow cytometry (PAFC) has demonstrated potential for early
      diagnosis of deadly diseases through detection of rare circulating tumor cells,
      pathogens, and clots in nearly the entire blood volume. Before clinical
      application, this promising diagnostic platform requires verification and
      optimization using adequate preclinical models. We show here that this can be
      addressed by examination of large mouse blood vessels which are similar in size,
      depth and flow velocity to human vessels used in PAFC. Using this model, we
      verified the capability of PAFC for ultrasensitive, noninvasive, label-free,
      rapid malaria diagnosis. The time-resolved detection of delayed PA signals from
      deep vessels provided complete elimination of background from strongly pigmented
      skin. We discovered that PAFC's sensitivity is higher during examination of
      infected cells in arteries compared to veins at similar flow rate. Our advanced
      PAFC platform integrating a 1060 nm laser with tunable pulse rate and width, a
      wearable probe with a focused transducer, and linear and nonlinear nanobubble
      amplified signal processing demonstrated detection of parasitemia at the
      unprecedented level of 0.00000001% within 20 seconds and the potential to further
      improve the sensitivity 100-fold in humans, that is approximately 106 times
      better than in existing malaria tests.

PMID- 27699127
TI  - Assessment of a multi-layered diffuse correlation spectroscopy method for
      monitoring cerebral blood flow in adults.
AB  - Diffuse correlation spectroscopy (DCS) is a promising technique for brain
      monitoring as it can provide a continuous signal that is directly related to
      cerebral blood flow (CBF); however, signal contamination from extracerebral
      tissue can cause flow underestimations. The goal of this study was to investigate
      whether a multi-layered (ML) model that accounts for light propagation through
      the different tissue layers could successfully separate scalp and brain flow when
      applied to DCS data acquired at multiple source-detector distances. The method
      was first validated with phantom experiments. Next, experiments were conducted in
      a pig model of the adult head with a mean extracerebral tissue thickness of 9.8
      +/- 0.4 mm. Reductions in CBF were measured by ML DCS and computed tomography
      perfusion for validation; excellent agreement was observed by a mean difference
      of 1.2 +/- 4.6% (CI95%: -31.1 and 28.6) between the two modalities, which was not
      significantly different.

PMID- 27699128
TI  - Unconstrained pulse pressure monitoring for health management using hetero-core
      fiber optic sensor.
AB  - In this paper, we present a pulse pressure waveform sensor that does not
      constrain a wearer's daily activity; the sensor uses hetero-core fiber optics.
      Hetero-core fiber sensors have been found to be sensitive to moderate bending. To
      detect minute pulse pressure changes from the radial artery at the wrist, we
      devised a fiber sensor arrangement using three-point bending supports. We
      analyzed and evaluated the measurement validity using wavelet transformation,
      which is well-suited for biological signal processing. It was confirmed that the
      detected pulse waveform had a fundamental mode frequency of around 1.25 Hz over
      the time-varying waveform. A band-pass filter with a range of frequencies from
      0.85 to 1.7 Hz was used to pick up the fundamental mode. In addition, a high-pass
      filter with 0.85 Hz frequency eliminated arm motion artifacts; consequently, we
      achieved high signal-to-noise ratio. For unrestricted daily health management, it
      is desirable that pulse pressure monitoring can be achieved by simply placing a
      device on the hand without the sensor being noticed. Two types of arrangements
      were developed and demonstrated in which the pulse sensors were either embedded
      in a base, such as an armrest, or in a wearable device. A wearable device without
      cuff pressure using a sensitivity-enhanced fiber sensor was successfully achieved
      with a sensitivity of 0.07-0.3 dB with a noise floor lower than 0.01 dB for
      multiple subjects.

PMID- 27699129
TI  - Motion quantification during multi-photon functional imaging in behaving animals.
AB  - Functional imaging in behaving animals is essential to understanding brain
      function. However, artifacts resulting from animal motion, including locomotion,
      can severely corrupt functional measurements. To dampen tissue motion, we
      designed a new optical window with minimal optical aberrations. Using the newly
      developed high-speed continuous volumetric imaging system based on an optical
      phase-locked ultrasound lens, we quantified motion of the cerebral cortex and
      hippocampal surface during two-photon functional imaging in behaving mice. We
      find that the out-of-plane motion is generally greater than the axial dimension
      of the point-spread-function during mouse locomotion, which indicates that high
      speed continuous volumetric imaging is necessary to minimize motion artifacts.

PMID- 27699130
TI  - Pencil beam all-optical ultrasound imaging.
AB  - A miniature, directional fibre-optic acoustic source is presented that employs
      geometrical focussing to generate a nearly-collimated acoustic pencil beam. When
      paired with a fibre-optic acoustic detector, an all-optical ultrasound probe with
      an outer diameter of 2.5 mm is obtained that acquires a pulse-echo image line at
      each probe position without the need for image reconstruction. B-mode images can
      be acquired by translating the probe and concatenating the image lines, and
      artefacts resulting from probe positioning uncertainty are shown to be
      significantly lower than those observed for conventional synthetic aperture
      scanning of a non-directional acoustic source. The high image quality obtained
      for excised vascular tissue suggests that the all-optical ultrasound probe is
      ideally suited for in vivo, interventional applications.

PMID- 27699131
TI  - Real-time in vivo diagnosis of laryngeal carcinoma with rapid fiber-optic Raman
      spectroscopy.
AB  - We assess the clinical utility of a unique simultaneous fingerprint (FP) (i.e.,
      800-1800 cm-1) and high-wavenumber (HW) (i.e., 2800-3600 cm-1) fiber-optic Raman
      spectroscopy for in vivo diagnosis of laryngeal cancer at endoscopy. A total of
      2124 high-quality in vivo FP/HW Raman spectra (normal = 1321; cancer = 581) were
      acquired from 101 tissue sites (normal = 71; cancer = 30) of 60 patients (normal
      = 44; cancer = 16) undergoing routine endoscopic examination. FP/HW Raman spectra
      differ significantly between normal and cancerous laryngeal tissue that could be
      attributed to changes of proteins, lipids, nucleic acids, and the bound water
      content in the larynx. Partial least squares-discriminant analysis and leave-one
      tissue site-out, cross-validation were employed on the in vivo FP/HW tissue Raman
      spectra acquired, yielding a diagnostic accuracy of 91.1% (sensitivity: 93.3%
      (28/30); specificity: 90.1% (64/71)) for laryngeal cancer identification, which
      is superior to using either FP (accuracy: 86.1%; sensitivity: 86.7% (26/30);
      specificity: 85.9% (61/71)) or HW (accuracy: 84.2%; sensitivity: 76.7% (23/30);
      specificity: 87.3% (62/71)) Raman technique alone. Further receiver operating
      characteristic analysis reconfirms the best performance of the simultaneous FP/HW
      Raman technique for laryngeal cancer diagnosis. We demonstrate for the first time
      that the simultaneous FP/HW Raman spectroscopy technique can be used for
      improving real-time in vivo diagnosis of laryngeal carcinoma during endoscopic
      examination.

PMID- 27699132
TI  - 3D imaging in CUBIC-cleared mouse heart tissue: going deeper.
AB  - The ability to acquire high resolution 3D images of the heart enables to study
      heart diseases more in detail. In this work, the CUBIC (clear, unobstructed brain
      imaging cocktails and computational analysis) clearing protocol was optimized for
      thick mouse heart sections to enhance the penetration depth of the confocal
      microscope lasers into the tissue. In addition, the optimized CUBIC clearing of
      the heart enhances antibody penetration into the tissue by a factor of five. The
      present protocol enables deep 3D high-quality image acquisition in the heart
      allowing a much more accurate assessment of the cellular and structural changes
      that underlie heart diseases.

PMID- 27699133
TI  - Classification of basal cell carcinoma in human skin using machine learning and
      quantitative features captured by polarization sensitive optical coherence
      tomography.
AB  - We report the first fully automated detection of basal cell carcinoma (BCC), the
      most commonly occurring type of skin cancer, in human skin using polarization
      sensitive optical coherence tomography (PS-OCT). Our proposed automated procedure
      entails building a machine-learning based classifier by extracting image features
      from the two complementary image contrasts offered by PS-OCT, intensity and phase
      retardation (PR), and selecting a subset of features that yields a classifier
      with the highest accuracy. Our classifier achieved 95.4% sensitivity and
      specificity, validated by leave-one-patient-out cross validation (LOPOCV), in
      detecting BCC in human skin samples collected from 42 patients. Moreover, we show
      the superiority of our classifier over the best possible classifier based on
      features extracted from intensity-only data, which demonstrates the significance
      of PR data in detecting BCC.

PMID- 27699134
TI  - Full-field interferometry for counting and differentiating aquatic biotic
      nanoparticles: from laboratory to Tara Oceans.
AB  - There is a huge abundance of viruses and membrane vesicles in seawater. We
      describe a new full-field, incoherently illuminated, shot-noise limited, common
      path interferometric detection method that we couple with the analysis of
      Brownian motion to detect, quantify, and differentiate biotic nanoparticles. We
      validated the method with calibrated nanoparticles and homogeneous DNA or RNA
      viruses. The smallest virus size that we characterized with a suitable signal-to
      noise ratio was around 30 nm in diameter. Analysis of Brownian motions revealed
      anisotropic trajectories for myoviruses.We further applied the method for
      vesicles detection and for analysis of coastal and oligotrophic samples from Tara
      Oceans circumnavigation.

PMID- 27699135
TI  - Imaging in turbid media: a transmission detector gives 2-3 order of magnitude
      enhanced sensitivity compared to epi-detection schemes.
AB  - Imaging depth in turbid media by two-photon fluorescence microscopy depends on
      the ability of the optical system to detect weak fluorescence signals. We have
      shown that use of a wide area detector in transmission geometry allows increasing
      imaging depth in turbid media due to efficient photon collection. Compared to the
      conventional epi-detection scheme used in most commercial microscopes, the
      transmission detector was found to be 2-3 orders of magnitude more sensitive when
      used for in depth imaging in scattering samples simulating brain optical
      properties.

PMID- 27699136
TI  - Terahertz transmission vs reflection imaging and model-based characterization for
      excised breast carcinomas.
AB  - This work presents experimental and analytical comparison of terahertz
      transmission and reflection imaging modes for assessing breast carcinoma in
      excised paraffin-embedded human breast tissue. Modeling for both transmission and
      reflection imaging is developed. The refractive index and absorption coefficient
      of the tissue samples are obtained. The reflection measurements taken at the
      system's fixed oblique angle of 30 degrees  are shown to be a hybridization of TE
      and TM modes. The models are validated with transmission spectroscopy at fixed
      points on fresh bovine muscle and fat tissues. Images based on the calculated
      absorption coefficient and index of refraction of bovine tissue are successfully
      compared with the terahertz magnitude and phase measured in the reflection mode.
      The validated techniques are extended to 20 and 30 MUm slices of fixed human
      lobular carcinoma and infiltrating ductal carcinoma mounted on polystyrene
      microscope slides in order to investigate the terahertz differentiation of the
      carcinoma with non-cancerous tissue. Both transmission and reflection imaging
      show clear differentiation in carcinoma versus healthy tissue. However, when
      using the reflection mode, in the calculation of the thin tissue properties, the
      absorption is shown to be sensitive to small phase variations that arise due to
      deviations in slide and tissue thickness and non-ideal tissue adhesion. On the
      other hand, the results show that the transmission mode is much less sensitive to
      these phase variations. The results also demonstrate that reflection imaging
      provides higher resolution and more clear margins between cancerous and
      fibroglandular regions, cancerous and fatty regions, and fibroglandular and fatty
      tissue regions. In addition, more features consistent with high power pathology
      images are exhibited in the reflection mode images.

PMID- 27699137
TI  - Time resolved diffuse optical spectroscopy with geometrically accurate models for
      bulk parameter recovery.
AB  - A novel straightforward, accessible and efficient approach is presented for
      performing hyperspectral time-domain diffuse optical spectroscopy to determine
      the optical properties of samples accurately using geometry specific models. To
      allow bulk parameter recovery from measured spectra, a set of libraries based on
      a numerical model of the domain being investigated is developed as opposed to the
      conventional approach of using an analytical semi-infinite slab approximation,
      which is known and shown to introduce boundary effects. Results demonstrate that
      the method improves the accuracy of derived spectrally varying optical properties
      over the use of the semi-infinite approximation.

PMID- 27699138
TI  - Procedures for risk-stratification of lung cancer using buccal nanocytology.
AB  - Lung cancer is the leading cause of cancer deaths in the U.S. with survival
      dramatically depending on stage at diagnosis. We had earlier reported that
      nanocytology of buccal cells can accurately risk-stratify smokers for the
      presence of early and late-stage lung cancer. To translate the technique into
      clinical practice, standardization of operating procedures is necessary to
      consistently yield precise and repeatable results. Here, we develop and validate
      simple, robust, and easily implementable procedures for specimen collection,
      processing, etc. in addition to a commercially-viable instrument prototype.
      Results of this work enable translation of the technology from academic lab to
      physicians' office.

PMID- 27699139
TI  - Targeted Theranostic Approach for Glioma Using Dendrimer-Based Curcumin
      Nanoparticle.
AB  - The delivery of anti-cancer agents to brain tumors represent a challenge because
      the blood-brain tumor barrier (BBTB) effectively limits the delivery of many
      agents. A new generation 3 (G3) dendrimer-based curcumin (Curc) conjugate was
      synthesized. The synthesized G3-Curc conjugate demonstrated full solubility in
      aqueous media. The in vitro study revealed that G3-Curc nanoparticles were
      internalized into glioma U-251 cells. Systemic delivery of G3-Curc conjugate led
      to preferentially accumulation in an orthotopic preclinical glioma model
      minimizing systemic toxic effect. Multicolor microscopy images of the tumor
      tissue showed that G3-Curc particles were internalized inside tumor cells
      selectively and further localized within nuclei. Enhanced bioavailability of G3
      Curc conjugate was also observed with improved therapeutic efficacy against
      different cancers cells.

PMID- 27699140
TI  - An Orbital Malignant Melanoma Arising in Cellular Blue Nevus in a Patient with
      Nevus of Ota.
AB  - Melanomas arising from orbital melanocytic proliferations are exceedingly rare.
      Many questions remain regarding their development and malignant transformation.
      We report on a 45-year-old Caucasian woman with a nevus of Ota that presented
      with visual disturbances involving her right eye and was found to have a biopsy
      proven cellular blue nevus in the orbital space. Five years later, she presented
      with proptosis and worsening symptoms. Biopsy at that time showed a cellular blue
      nevus with areas of melanoma. We conclude that patients with a nevus of Ota or an
      orbital cellular blue nevus, particularly Caucasians, should be monitored for
      ocular/orbital involvement and followed closely for signs of rapid growth. There
      may be a progressive evolution to melanoma from a blue nevus.

PMID- 27699141
TI  - Post-Treatment Gliosarcoma Extension into the Pterygomaxillary Fossa: Literature
      Review and Case Report.
AB  - Only four primary gliosarcoma case reports are described in the literature with
      transcranial (intradural to extradural) penetration into the region of the
      infratemporal fossa. This is the first report of a primary glioblastoma (GBM)
      that evolved into secondary or post-treatment gliosarcoma without evidence of a
      second de novo tumor and with extension into the left pterygomaxillary fossa.

PMID- 27699142
TI  - Persistence of a Cervical Neck Mass, Not Just the Lymphoma.
AB  - Actinomycosis is a rare, chronic granulomatous infection caused by gram-positive,
      anaerobic to microaerophilic branching filamentous bacteria. In the cervicofacial
      region, it usually presents as an enlarging neck mass. It remains a diagnostic
      challenge due to the fact that cultures show no growth in more than 50% of cases.
      We report a case of a 67-year-old patient known to have a neck mass secondary to
      lymphoma in which the neck mass persisted despite therapy. Upon evaluation, the
      diagnosis of culture-negative actinomycosis was based on histopathology findings,
      and the patient received antibiotic therapy. We will discuss the diagnosis and
      pathology of actinomycosis, attempting to explore the relationship between
      actinomycosis and lymphoid malignancy.

PMID- 27699144
TI  - Identifying metabolic syndrome in a clinical cohort: Implications for prevention
      of chronic disease.
AB  - In the clinical setting, calculating cardiovascular disease (CVD) risk is
      commonplace but the utility of the harmonised equation for metabolic syndrome
      (MetS) (Alberti et al., 2009) is less well established. The aims of this study
      were to apply this equation to an overweight clinical cohort to identify risk
      factors for being metabolically unhealthy and explore associations with chronic
      disease. Baseline data were analysed from a lifestyle intervention trial of
      Illawarra residents recruited in 2014/2015. Participants were aged 25-54 years
      with a BMI 25-40 kg/m2. Data included MetS, CVD risk, insulin sensitivity,
      weight, body fat, diet, peripheral artery disease (PAD), physical activity, socio
      economic position and psychological profile. Backward stepwise regression tested
      the association of covariates with MetS status and linear or logistic regression
      tested associations between MetS and risk of CVD, coronary heart disease, PAD and
      insulin resistance. 374 participants were included in the analysis with 127
      (34.0%) categorised with MetS. Covariates significantly and positively associated
      with MetS were higher BMI (odds 1.26, p < 0.01) and older age (odds 1.08, p <
      0.01). MetS participants (n = 351) had a 4.50% increase in CVD risk and were 8.1
      and 12.7 times (respectively) more likely to be at risk of CHD and insulin
      resistance, compared to participants without MetS. The utility of the harmonised
      equation in the clinical setting was confirmed in this overweight clinical
      cohort. Those classified as having MetS were more likely to be older,
      overweight/obese individuals and they had a substantially higher risk of
      developing CVD and insulin resistance than those without MetS.

PMID- 27699143
TI  - Photoacoustic Flow Cytometry for Single Sickle Cell Detection In Vitro and In
      Vivo.
AB  - Control of sickle cell disease (SCD) stage and treatment efficiency are still
      time-consuming which makes well-timed prevention of SCD crisis difficult. We show
      here that in vivo photoacoustic (PA) flow cytometry (PAFC) has a potential for
      real-time monitoring of circulating sickled cells in mouse model. In vivo data
      were verified by in vitro PAFC and photothermal (PT) and PA spectral imaging of
      sickle red blood cells (sRBCs) expressing SCD-associated hemoglobin (HbS)
      compared to normal red blood cells (nRBCs). We discovered that PT and PA signal
      amplitudes from sRBCs in linear mode were 2-4-fold lower than those from nRBCs.
      PT and PA imaging revealed more profound spatial hemoglobin heterogeneity in
      sRBCs than in nRBCs, which can be associated with the presence of HbS clusters
      with high local absorption. This hypothesis was confirmed in nonlinear mode
      through nanobubble formation around overheated HbS clusters accompanied by
      spatially selective signal amplification. More profound differences in absorption
      of sRBCs than in nRBCs led to notable increase in PA signal fluctuation
      (fluctuation PAFC mode) as an indicator of SCD. The obtained data suggest that
      noninvasive label-free fluctuation PAFC has a potential for real-time enumeration
      of sRBCs both in vitro and in vivo.

PMID- 27699145
TI  - The relationship between physical activity, sleep duration and depressive
      symptoms in older adults: The English Longitudinal Study of Ageing (ELSA).
AB  - Research to date suggests that physical activity (PA) is associated with distinct
      aspects of sleep, but studies have predominantly focused on sleep quality, been
      carried out in younger adults, and have not accounted for many covariates. Of
      particular interest is also the reported relationship between physical activity
      and depression in older adults and as such, their associations with sleep
      duration. Here we examine the cross-sectional relation between physical activity
      and sleep duration in a community-dwelling sample of 5265 older adults from the
      English Longitudinal Study of Ageing. We analysed the data using multiple
      regression, with physical activity as a categorical exposure and sleep duration a
      continuous outcome, as well as testing the interaction between physical activity
      and depressive symptoms, which was significant (p < 0.001). We therefore
      stratified our analyses by depressive symptomatology. Our main finding was that,
      in the group with elevated depressive symptoms only, physical activity was
      positively associated with sleep duration in models adjusted for all covariates
      (age, sex, wealth, ethnicity, smoking, alcohol consumption, BMI, long-standing
      illness) across low [B (mean difference in sleep duration) = 25.22 min, 95% CI =
      (3.72; 46.72)], moderate [B = 27.92 min, 95% CI = (6.59; 49.26)] and high [B =
      31.65 min, 95% CI = (7.36; 55.94)] PA groups, in comparison to the sedentary
      group. However, we observed no relation between physical activity and sleep
      duration in respondents who reported no depressive symptoms, irrespective of
      physical activity level (p > 0.05). Our findings suggest that a potentially
      effective way of improving sleep in older adults with depressive symptoms is via
      physical activity interventions.

PMID- 27699146
TI  - Evidence of delayed dissemination or re-infection with Blastomyces in two
      immunocompetent hosts.
AB  - Relapse or recurrence of blastomycosis in patients is rare. Re-infection of a
      patient with blastomycosis has not been previously reported. In this report, we
      describe relapse or reinfection with Blastomyces in 2 immunocompetent patients.
      This is the first study in which genetic typing was performed on paired
      Blastomyces isolates from the same patient obtained months apart.

PMID- 27699147
TI  - Onychomycosis due to Chaetomium globosum with yellowish black discoloration and
      periungual inflammation.
AB  - Onychomycosis is usually caused by dermatophytes, although also other filamentous
      and yeast-like fungi are associated with nail invasion. Chaetomium is an
      environmental genus of ascomycetes exhibiting a certain degree of
      extremotolerance. We report the first case of onychomycosis in a 46-year-old
      woman in China caused by Chaetomium globosum. The patient showed yellowish black
      discoloration with periungual inflammation on the left first toenail. We
      confirmed the causative agent, C. globosum, by KOH mount, culture,
      micromorphology and DNA sequence analysis.

PMID- 27699149
TI  - Expression of P40 and P63 in lung cancers using fine needle aspiration cases.
      Understanding clinical pitfalls and limitations.
AB  - BACKGROUND: Fine-needle aspiration (FNA) biopsy of lung lesions is a highly
      accurate method for diagnosing and staging of lung cancers, particularly in
      patients with advanced cancer. Although, the majority of FNA cases of non-small
      cell lung carcinoma (NSCLC) can be subclassified by hematoxylin and eosin (H&E)
      sections, immunohistochemical (IHC) markers are usually necessary for difficult
      cases. Our previous study has shown that both P40 and P63 demonstrate
      differential sensitivity and specificity in the subclassification of squamous
      cell carcinoma (SqCC) using tumor tissue microarrays (TMA). In the present study,
      we further evaluated the utility of P40 and P63 and the potential pitfalls and
      limitations associated with the usefulness of these stains in FNA cases. METHODS:
      By a computer search of pathology archives, 144 FNA biopsies with diagnoses of
      lung cancers and P40/P63 stains were identified, including 50 adenocarcinomas
      (ADCs), 56 SqCCs, 8 small cell lung carcinomas (SCLCs), and 12 cases of poorly
      differentiated carcinoma (PD CA). Ten benign FNA lung lesions and 8 other
      malignant neoplasms were also included as controls. Nuclear staining patterns of
      P40 and P63 were scored semi-quantitatively as 0 (negative), 1 (<10%, weak and
      focal), or 2 (>10%, strong and diffuse). RESULTS: In lung SqCCs, P40 and P63 were
      positive in 77.3% and 89.5% cases, respectively. In ADCs, P40 was weakly and
      focally positive in 6.1% cases, and P63 was variably positive in 62.8% cases. In
      SCLCs, P40 and P63 were focally positive in 12.5% and 50% cases. In PD CAs, no
      P40 or P63 immunoreactivity was detected. In the group of other neoplasms (n=8)
      both P40 and P63 were positive in the case of metastatic non-seminomatous germ
      cell tumor (NSGCT) (n=1), and P63 was positive in the case of metastatic Merkel
      cell carcinoma (n=1). The sensitivity and specificity of P40 and P63 were
      76.9%/93.3%, and 90.2%/50.7% in the lung SqCC. CONCLUSIONS: P63 has a better
      sensitivity, and P40 has a better specificity for SqCC. A positive staining
      pattern with both markers was also found in certain non-SqCC cases. Recognizing
      limitations of these markers are particularly important in FNA cases.

PMID- 27699150
TI  - Draft genome sequence of Microbacterium oleivorans strain Wellendorf implicates
      heterotrophic versatility and bioremediation potential.
AB  - Microbacterium oleivorans is a predominant member of hydrocarbon-contaminated
      environments. We here report on the genomic analysis of M. oleivorans strain
      Wellendorf that was isolated from an indoor door handle. The partial genome of M.
      oleivorans strain Wellendorf consists of 2,916,870 bp of DNA with 2831 protein
      coding genes and 49 RNA genes. The organism appears to be a versatile mesophilic
      heterotroph potentially capable of hydrolysis a suite of carbohydrates and amino
      acids. Genomic analysis revealed metabolic versatility with genes involved in the
      metabolism and transport of glucose, fructose, rhamnose, galactose, xylose,
      arabinose, alanine, aspartate, asparagine, glutamate, serine, glycine, threonine
      and cysteine. This is the first detailed analysis of a Microbacterium oleivorans
      genome.

PMID- 27699148
TI  - Effects of craving behavioral intervention on neural substrates of cue-induced
      craving in Internet gaming disorder.
AB  - Internet gaming disorder (IGD) is characterized by high levels of craving for
      online gaming and related cues. Since addiction-related cues can evoke increased
      activation in brain areas involved in motivational and reward processing and may
      engender gaming behaviors or trigger relapse, ameliorating cue-induced craving
      may be a promising target for interventions for IGD. This study compared neural
      activation between 40 IGD and 19 healthy control (HC) subjects during an Internet
      gaming cue-reactivity task and found that IGD subjects showed stronger activation
      in multiple brain areas, including the dorsal striatum, brainstem, substantia
      nigra, and anterior cingulate cortex, but lower activation in the posterior
      insula. Furthermore, twenty-three IGD subjects (CBI + group) participated in a
      craving behavioral intervention (CBI) group therapy, whereas the remaining 17 IGD
      subjects (CBI - group) did not receive any intervention, and all IGD subjects
      were scanned during similar time intervals. The CBI + group showed decreased IGD
      severity and cue-induced craving, enhanced activation in the anterior insula and
      decreased insular connectivity with the lingual gyrus and precuneus after
      receiving CBI. These findings suggest that CBI is effective in reducing craving
      and severity in IGD, and it may exert its effects by altering insula activation
      and its connectivity with regions involved in visual processing and attention
      bias.

PMID- 27699152
TI  - Immunologic factors may play a role in herpes simplex virus 1 reactivation in the
      brain and retina after influenza vaccination.
AB  - Herpes simplex virus 1 (HSV-1) is a nearly ubiquitous human pathogen, remaining
      dormant in its human host the majority of the time. The interaction between HSV-1
      and the immune system represents a complicated balance of power that allows the
      virus to persist in the host for a lifetime. However, disruptions in the immune
      system can activate the virus with the potential to cause devastating infections
      in the central nervous system (CNS). We present a patient who suffered three
      consecutive yearly HSV-1 CNS episodes (encephalitis, seizure, and retinitis),
      each within days of his influenza vaccination. We highlight subtle immunologic
      defects in this patient that may have allowed unchecked viral replication and
      resultant disease manifestations, as well as the potential role of influenza
      vaccine in tipping this balance in favor of HSV-1.

PMID- 27699151
TI  - Draft genome sequence and detailed analysis of Pantoea eucrina strain Russ and
      implication for opportunistic pathogenesis.
AB  - The genus Pantoea is a predominant member of host-associated microbiome. We here
      report on the genomic analysis of Pantoea eucrina strain Russ that was isolated
      from a trashcan at Oklahoma State University, Stillwater, OK. The draft genome of
      Pantoea eucrina strain Russ consists of 3,939,877 bp of DNA with 3704 protein
      coding genes and 134 RNA genes. This is the first report of a genome sequence of
      a member of Pantoea eucrina. Genomic analysis revealed metabolic versatility with
      genes involved in the metabolism and transport of all amino acids as well as
      glucose, fructose, mannose, xylose, arabinose and galactose, suggesting the
      organism is a versatile heterotroph. The genome also encodes an extensive
      secretory machinery including types I, II, III, IV, and Vb secretion systems, and
      several genes for pili production including the new usher/chaperone system (pfam
      05,229). The implications of these systems for opportunistic pathogenesis are
      discussed.

PMID- 27699153
TI  - Bone mineral density in mucopolysaccharidosis IVB.
AB  - To date, the only published reports of bone mineral density (BMD) in MPS IV
      involve patients with MPS IVA; no reports exist describing BMD for MPS IVB. In
      this prospective study of BMD in three patients with MPS IVB, BMD was acquired by
      dual-energy X-ray absorptiometry (DXA) at whole body (WB), lumbar spine (LS), and
      lateral distal femur (LDF). Functional abilities, ambulatory status, medical
      history, and height z-score were evaluated. Three patients with MPS IVB (two
      females), aged 17.7, 31.4 and 31.7 years, were evaluated. Every patient was
      ambulatory and one sustained two fractures caused by trauma. Whole body and hip
      DXA scans were technically invalid in every patient due to the presence of
      prosthetic hip hardware. Lumbar spine was valid in only 1 patient due skeletal
      abnormalities, and was normal (Z-score of - 0.8). The LDF was valid in every
      patient and was low at all three regions of interest: average LDF z-scores were -
      3.1 (range, - 2.9 to - 3.6), - 2.3 (range, - 2.0 to - 2.5), and - 2.1 (range, -
      2.0 to - 2.3) for region 1-region 3, respectively. Patients with MPS IVB have low
      BMD of the lower extremities even with full-time ambulation. Routine body sites
      to measure by DXA were problematic; hip and WB were invalid due to artifact, and
      LS had limited utility. The LDF was the only body site consistently available on
      all patients. Patients did not experience low-energy fractures despite low BMD.

PMID- 27699154
TI  - Methylmalonyl-coA epimerase deficiency: A new case, with an acute metabolic
      presentation and an intronic splicing mutation in the MCEE gene.
AB  - Methylmalonyl-coA epimerase (MCE) follows propionyl-coA carboxylase and precedes
      methylmalonyl-coA mutase in the pathway converting propionyl-coA to succinyl-coA.
      MCE deficiency has previously been described in six patients, one presenting with
      metabolic acidosis, the others with nonspecific neurological symptoms or
      asymptomatic. The clinical significance and biochemical characteristics of this
      rare condition have been incompletely defined. We now describe a patient who
      presented acutely at 5 years of age with vomiting, dehydration, confusion, severe
      metabolic acidosis and mild hyperammonemia. At presentation, organic acid
      profiles were dominated by increased ketones and 3-hydroxypropionate, with
      moderately elevated methylcitrate and propionylglycine, and acylcarnitine
      profiles showed marked C3 (propionylcarnitine) elevation with normal C4DC
      (methylmalonylcarnitine + succinylcarnitine). Propionic acidemia was initially
      suspected, but it was subsequently noted that methylmalonic acid was mildly but
      persistently elevated in urine, and clearly elevated in plasma and cerebrospinal
      fluid. The overall biochemical profile prompted consideration of MCE deficiency.
      Studies on cultured fibroblasts showed moderately decreased propionate
      incorporation. Complementation analysis permitted assignment to the MCEE group. A
      heterozygous p.Arg47Ter (p.R47*) mutation in the MCEE gene was identified by
      sequencing of exons, and RNA studies identified a novel intronic splicing
      mutation, c.379-644A > G, confirming the diagnosis of MCE deficiency. Following
      the initial severe presentation, development has been normal and the clinical
      course over the subsequent six years has remained relatively uneventful on an
      essentially normal diet. This report contributes to the clinical and biochemical
      characterisation of this rare disorder, while highlighting potential causes of
      under-diagnosis or of diagnostic confusion.

PMID- 27699155
TI  - Androgen-Deprivation Therapy and Cardiovascular Disease Risk - The Role of
      Exercise in Prostate Cancer Treatment.

PMID- 27699157
TI  - Association of Nitric Oxide Levels and Endothelial Nitric Oxide Synthase G894T
      Polymorphism with Coronary Artery Disease in the Iranian Population.
AB  - PURPOSE: The endothelial nitric oxide synthase (eNOS) G894T polymorphism has been
      reported to cause endothelial dysfunction and may have a role in the development
      of coronary artery disease (CAD). The aim of the present study was to investigate
      the association of eNOS G894T genetic polymorphism and plasma levels of nitric
      oxide (NO) with CAD risk in an Iranian population. MATERIALS AND METHODS: We
      studied 200 patients with angiographically documented CAD and 100 matched
      controls. Analysis of G894T genetic polymorphism of eNOS was performed by
      polymerase chain reaction-restriction fragment length polymorphism method. Plasma
      levels of NO were determined using Griess method. Biochemical analysis was
      conducted by routine colorimetric methods. RESULTS: Plasma levels of NO were
      significantly lower in CAD patients than control subjects (41.60+/-12.70 vs.
      55.48+/-16.57, P=0.001). Also, the mean plasma levels of NO were significantly
      lower in T allele carriers of eNOS G894T polymorphism than G allele carriers
      (P<0.001). The genotype distribution and minor T allele frequency of eNOS G894T
      polymorphism significantly differed between CAD patients and control subjects
      (P<0.05). However, no significant association was found between the eNOS G894T
      polymorphism and the severity of CAD (number of diseased vessel) or the lipid
      profile of CAD patients (P>0.05). CONCLUSION: Reduced plasma level of NO is
      associated with increased risk of CAD in our population. Moreover, eNOS G894T
      polymorphism is a significant risk factor for CAD development via reducing the
      plasma levels of NO. However, eNOS G894T polymorphism is not a contributing
      factor for the severity of CAD.

PMID- 27699158
TI  - Outcomes of Arteriovenous Fistula for Hemodialysis in Pediatric and Adolescent
      Patients.
AB  - PURPOSE: This retrospective review aimed to report the outcomes of arteriovenous
      fistula (AVF) and to evaluate the suitability of AVF as a permanent vascular
      access in pediatric populations. MATERIALS AND METHODS: Data were collected for
      all patients aged 0 to 19 years who underwent AVF creation for hemodialysis
      between January 2000 and June 2014. RESULTS: Fifty-two AVFs were created in 47
      patients. Mean age was 15.7+/-3.2 years and mean body weight was 46.7+/-15.4 kg.
      Of the 52 AVFs, 43 were radiocephalic AVFs, 7 were brachiocephalic AVFs and 2
      were basilic vein transpositions. With a mean follow-up of 49.7+/-39.2 months,
      primary patency was 60.5%, 51.4%, and 47.7% at 1, 3, and 5 years, respectively
      and secondary patency was 82.7%, 79.2% and 79.2% at 1, 3, and 5 years,
      respectively. Age, body weight, AVF type, the presence of a central venous
      catheter, use of anticoagulation therapy, and history of vascular access failure
      were not significantly associated with patency rates. There were 9 cases (17.3%)
      of primary failure; low body weight was an independent predictor. Excluding cases
      of primary failure, the mean duration of maturation was 10.0+/-3.7 weeks. During
      follow-up, 20 patients (42.6%) underwent kidney transplantation, with a median
      interval to transplantation of 36 months. CONCLUSION: AVF creation in children
      and adolescents is associated with acceptable long-term durability, primary
      failure rate and maturation time. Considering the waiting time and limited kidney
      graft survival, placement of AVFs should be considered primarily even in patients
      expected to receive transplantation.

PMID- 27699159
TI  - Bilateral Type IIIa Endoleak and Disconnection of Both Limbs after Evar with an
      Endurant II Endograft.
AB  - A 75-year-old patient with severe comorbidities was treated with an Endurant(r)
      (Medtronic, USA) II endograft due to a ruptured abdominal aortic aneurysm (AAA).
      After four years of unremarkable follow-up, bilateral limb separation was
      detected. The patient underwent endovascular bridging without any complication.
      Although rarely detected in newer grafts, late bilateral type IIIa endoleaks can
      present and should be promptly repaired. Complex or ruptured AAAs treated with
      off-label use of endografts should be under closer surveillance using imaging
      tools for potential endoleaks or aneurysm sac growth.

PMID- 27699160
TI  - Cystic Disease of the Groin Presenting as Compression of a Femoral Vessel.
AB  - In this study, we describe our diagnosis and treatment of two patients who
      presented with femoral vessel compression caused by a cystic lesion in the groin.
      One case was diagnosed as adventitial cystic disease (ACD) of the common femoral
      artery resulting in leg claudication and the other was diagnosed as a ganglion
      cyst (GC) causing femoral vein compression and unilateral leg swelling. The
      operative findings differed between these two cases with respect to the
      dissection of the cyst and femoral vessel, but the postoperative histological
      examination results were similar. The pathogenesis of ACD and GC is not fully
      understood, and further investigation is needed to delineate the exact pathology
      of these uncommon conditions.

PMID- 27699161
TI  - Intensive Long Distance Running as a Possible Cause of Multiple Splanchnic
      Arterial Aneurysms: A Case Report.
AB  - This is a case report that suggests the possible association between multiple
      splanchnic arterial aneurysms and long-distance running. The clinical features of
      one patient admitted at Chungbuk National University Hospital for treatment of
      multiple splanchnic arterial aneurysms were reviewed. A 54-year-old man had a
      recurrent, intermittent and epigastric pain for 2 months. There was no
      abnormality in gastroscopy and colonoscopy. An abdominal computed tomography
      angiography documented calcified superior mesenteric artery (SMA) and splenic
      artery aneurysms. The patient had a history of recreational long-distance running
      for over 10 years. His average running time per week was more than 10 hours.
      There was no evidence of systemic arteritis, connective tissue disorder or
      infectious process that may have caused the aneurysms. He did not take any drugs.
      The SMA aneurysm was opened, and the aneurysmal segment of SMA was replaced with
      a vein graft. The splenic aneurysm was observed. The patient recovered without
      any sequelae.

PMID- 27699162
TI  - Bovine Aortic Arch and Bilateral Retroesophageal Course of Common Carotid
      Arteries in a Symptomatic Patient.
AB  - Anatomical variations of carotid arteries may be related to their development
      (agenesis, aplasia, hypoplasia) or course (coiling, kinking, tortuosity). Partial
      or total aberrancies in carotid vessel anatomy rarely occur. We describe the case
      of a 95-year-old woman presented with sudden onset of confusion and
      disorientation together with upper limb clonus. Computed tomography (CT)-scan
      revealed a left frontal brain injury with a not conclusive carotid doppler
      ultrasound. CT angiography reported a bovine aortic arch with bilateral
      retroesophageal course of both common carotid arteries and left severe (>70%)
      internal carotid artery stenosis. The knowledge of anatomical variations of the
      course of carotid arteries is relevant for possible surgical or endovascular
      repair or in case of otolaryngology or intubation procedures.

PMID- 27699163
TI  - Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
      Findings of Post Traumatic Lymphangioma in a Young Adult Male.
AB  - The authors report the case of a 34-year-old male, who underwent a fluorine-18
      fluoro deoxyglucose (18F-FDG) positron emission tomography/computed tomography
      (PET/CT) scan 7 years after trauma for the evaluation of multifocal masses in the
      right iliac and right inguinal areas. CT findings showed multifocal low density
      masses and 18F-FDG PET revealed slightly increased uptake (maximum standardized
      uptake value [SUVmax] 3.1). These findings did not exclude the possibility of a
      benign or malignant lesion. To achieve differential diagnosis, partial surgical
      excision was performed and a pathologic examination subsequently revealed
      lymphangioma. Here, the authors describe the 18F-FDG PET/CT findings of a rare
      case of lymphangioma resulting from trauma.

PMID- 27699165
TI  - Birth Spacing of Pregnant Women in Nepal: A Community-Based Study.
AB  - BACKGROUND: Optimal birth spacing has health advantages for both mother and
      child. In developing countries, shorter birth intervals are common and associated
      with social, cultural, and economic factors, as well as a lack of family
      planning. This study investigated the first birth interval after marriage and
      preceding interbirth interval in Nepal. METHODS: A community-based prospective
      cohort study was conducted in the Kaski district of Nepal. Information on birth
      spacing, demographic, and obstetric characteristics was obtained from 701
      pregnant women using a structured questionnaire. Logistic regression analyses
      were performed to ascertain factors associated with short birth spacing. RESULTS:
      About 39% of primiparous women gave their first child birth within 1 year of
      marriage and 23% of multiparous women had short preceding interbirth intervals
      (<24 months). The average birth spacing among the multiparous group was 44.9 (SD
      21.8) months. Overall, short birth spacing appeared to be inversely associated
      with advancing maternal age. For the multiparous group, Janajati and lower caste
      women, and those whose newborn was female, were more likely to have short birth
      spacing. CONCLUSION: The preceding interbirth interval was relatively long in the
      Kaski district of Nepal and tended to be associated with maternal age, caste, and
      sex of newborn infant. Optimal birth spacing programs should target Janajati and
      lower caste women, along with promotion of gender equality in society.

PMID- 27699156
TI  - Diagnosis and Treatment of Lower Extremity Deep Vein Thrombosis: Korean Practice
      Guidelines.
AB  - Lower extremity deep vein thrombosis is a serious medical condition that can
      result in death or major disability due to pulmonary embolism or post-thrombotic
      syndrome. Appropriate diagnosis and treatment are required to improve symptoms
      and salvage the affected limb. Early thrombus clearance rapidly resolves symptoms
      related to venous obstruction, restores valve function and reduces the incidence
      of post-thrombotic syndrome. Recently, endovascular treatment has been
      established as a standard method for early thrombus removal. However, there are a
      variety of views regarding the indications and procedures among medical
      institutions and operators. Therefore, we intend to provide evidence-based
      guidelines for diagnosis and treatment of lower extremity deep vein thrombosis by
      multidisciplinary consensus. These guidelines are the result of a close
      collaboration between interventional radiologists and vascular surgeons. The
      goals of these guidelines are to improve treatment, to serve as a guide to the
      clinician, and consequently to contribute to public health care.

PMID- 27699164
TI  - Exploring Changes in Two Types of Self-Efficacy Following Participation in a
      Chronic Disease Self-Management Program.
AB  - Chronic conditions and falls are related issues faced by many aging adults.
      Stanford's Chronic Disease Self-Management Program (CDSMP) added brief fall
      related content to the standardized 6-week workshop; however, no research had
      examined changes in Fall-related self-efficacy (SE) in response to CDSMP
      participation. This study explored relationships and changes in SE using the SE
      to manage chronic disease scale (SEMCD Scale) and the Fall Efficacy Scale (FallE
      Scale) in participants who successfully completed CDSMP workshops within a
      Southern state over a 10-month period. SE scale data were compared at baseline
      and post-intervention for 36 adults (mean age = 74.5, SD = +/-9.64). Principal
      component analysis (PCA), using oblimin rotation was completed at baseline and
      post-intervention for the individual scales and then for analysis combining both
      scales as a single scale. Each scale loaded under a single component for the PCA
      at both baseline and post-intervention. When both scales were entered as single
      meta-scale, the meta-scale split along two factors with no double loading. SEMCD
      and FallE Scale scores were significantly correlated at baseline and post
      intervention, at least p < 0.05. A significant proportion of participants
      improved their scores on the FallE Scale post-intervention (p = 0.038). The
      magnitude of the change was also significant only for the FallE Scale (p =
      0.043). The SEMCD Scale scores did not change significantly. Study findings from
      the exploratory PCA and significant correlations indicated that the SEMCD Scale
      and the FallE Scale measured two distinct but related types of SE. Though the
      scale scores were correlated at baseline and post-intervention, only the FallE
      Scale scores significantly differed post-intervention. Given this relationship
      and CDSMP's recent addition of a 10-min fall prevention segment, further
      exploration of CDSMP's possible influence on Fall-related SE would provide useful
      understanding for health promotion in aging adults.

PMID- 27699166
TI  - The Brief Symptom Inventory and the Outcome Questionnaire-45 in the Assessment of
      the Outcome Quality of Mental Health Interventions.
AB  - Self-report questionnaires are economical instruments for routine outcome
      assessment. In this study, the performance of the German version of the Outcome
      Questionnaire-45 (OQ-45) and the Brief Symptom Inventory (BSI) was evaluated when
      applied in analysis of the outcome quality of psychiatric and psychotherapeutic
      interventions. Pre-post data from two inpatient samples (N = 5711) and one
      outpatient sample (N = 239) were analyzed. Critical differences (reliable change
      index) and cut-off points between functional and dysfunctional populations were
      calculated using the Jacobson and Truax method of calculating clinical
      significance. Overall, the results indicated that the BSI was more accurate than
      the OQ-45 in correctly classifying patients as clinical subjects. Nonetheless,
      even with the BSI, about 25% of inpatients with schizophrenia attained a score at
      admission below the clinical cut-off. Both questionnaires exhibited the highest
      sensitivity to psychopathology with patients with personality disorders. When
      considering the differences in the prescores, both questionnaires showed the same
      sensitivity to change. The advantage of using these self-report measures is
      observed primarily in assessing outpatient psychotherapy outcome. In an inpatient
      setting two main problems-namely, the low response rate and the scarce
      sensitivity to psychopathology with severely ill patients-limit the usability of
      self-report questionnaires.

PMID- 27699167
TI  - Obstructive Sleep Apnea in Women: Specific Issues and Interventions.
AB  - Obstructive sleep apnea (OSA) has traditionally been seen as a male disease.
      However, the importance of OSA in women is increasingly being recognized, along
      with a number of significant gender-related differences in the symptoms,
      diagnosis, consequences, and treatment of OSA. Women tend to have less severe OSA
      than males, with a lower apnea-hypopnea index (AHI) and shorter apneas and
      hypopneas. Episodes of upper airway resistance that do not meet the criteria for
      apneas are more common in women. Prevalence rates are lower in women, and
      proportionally fewer women receive a correct diagnosis. Research has also
      documented sex differences in the upper airway, fat distribution, and respiratory
      stability in OSA. Hormones are implicated in some gender-related variations, with
      differences between men and women in the prevalence of OSA decreasing as age
      increases. The limited data available suggest that although the prevalence and
      severity of OSA may be lower in women than in men, the consequences of the
      disease are at least the same, if not worse for comparable degrees of severity.
      Few studies have investigated gender differences in the effects of OSA treatment.
      However, given the differences in physiology and presentation, it is possible
      that personalized therapy may provide more optimal care.

PMID- 27699169
TI  - Analysis of the Influence of Complexity and Entropy of Odorant on Fractal
      Dynamics and Entropy of EEG Signal.
AB  - An important challenge in brain research is to make out the relation between the
      features of olfactory stimuli and the electroencephalogram (EEG) signal. Yet, no
      one has discovered any relation between the structures of olfactory stimuli and
      the EEG signal. This study investigates the relation between the structures of
      EEG signal and the olfactory stimulus (odorant). We show that the complexity of
      the EEG signal is coupled with the molecular complexity of the odorant, where
      more structurally complex odorant causes less fractal EEG signal. Also, odorant
      having higher entropy causes the EEG signal to have lower approximate entropy.
      The method discussed here can be applied and investigated in case of patients
      with brain diseases as the rehabilitation purpose.

PMID- 27699168
TI  - The Endothelial Glycocalyx: New Diagnostic and Therapeutic Approaches in Sepsis.
AB  - Sepsis is defined as a life-threatening organ dysfunction caused by a
      dysregulated host response to infection. The endothelial glycocalyx is one of the
      earliest sites involved during sepsis. This fragile layer is a complex network of
      cell-bound proteoglycans, glycosaminoglycan side chains, and sialoproteins lining
      the luminal side of endothelial cells with a thickness of about 1 to 3 MUm.
      Sepsis-associated alterations of its structure affect endothelial permeability
      and result in the liberation of endogenous damage-associated molecular patterns
      (DAMPs). Once liberated in the circulatory system, DAMPs trigger the devastating
      consequences of the proinflammatory cascades in sepsis and septic shock. In this
      way, the injury to the glycocalyx with the consecutive release of DAMPs
      contributes to a number of specific clinical effects of sepsis, including acute
      kidney injury, respiratory failure, and septic cardiomyopathy. Moreover, the
      extent of glycocalyx degradation serves as a marker of endothelial dysfunction
      and sepsis severity. In this review, we highlight the crucial role of the
      glycocalyx in sepsis as a diagnostic tool and discuss the potential of members of
      the endothelial glycocalyx serving as hopeful therapeutic targets in sepsis
      associated multiple organ failures.

PMID- 27699170
TI  - Network Based Approach in the Establishment of the Relationship between Type 2
      Diabetes Mellitus and Its Complications at the Molecular Level Coupled with
      Molecular Docking Mechanism.
AB  - Diabetes mellitus (DM) is one of the major metabolic disorders that is currently
      threatening the world. DM is seen associated with obesity and diabetic
      retinopathy (DR). In the present paper we tried to evaluate the relationship
      between the three aliments at the gene level and further performed the molecular
      docking to identify the common drug for all the three diseases. We have adopted
      several software programs such as Phenopedia, VennViewer, and CDOCKER to
      accomplish the objective. Our results revealed six genes that commonly associated
      and are involved in the signalling pathway. Furthermore, evaluation of common
      gene association from the selected set of genes projected the presence of SIRT1
      in all the three aliments. Therefore, we targeted protein 4KXQ which was produced
      from the gene SIRT1 and challenged it with eight phytochemicals, adopting the
      CDOCKER. C1 compound has displayed highest -CDOCKER energy and -CDOCKER
      interaction energy of 43.6905 and 43.3953, respectively. Therefore, this compound
      is regarded as the most potential lead molecule.

PMID- 27699171
TI  - Effect of Dissection and Reconstruction of Palatal Muscles on Morphological
      Features and Ultrastructure of the Oral Musculature in Cats.
AB  - The study was designed to determine the effect of dissection and reconstruction
      of palatal muscles on muscle morphology in cats. 27 cats were randomly divided
      into three groups according to the extent of muscle dissection from the palatal
      midline. All dissections were performed from the posterior border of the hard
      palate, and the muscles were allowed to reconstruct over time. The morphological
      features were determined by hematoxylin and eosin staining of tissue sections,
      and ultrastructure was observed under a transmission electron microscope. As a
      result, no obvious differences were evident in the morphological features or
      ultrastructure of animals in the <1/3rd and 1/3rd-2/3rd area groups. In the
      >2/3rd area group, the muscles fibers were disordered and inflammatory cell
      infiltration and naive muscle cells were found at one month after surgery. At the
      second and third month after surgery, the muscle fibers showed regular alignment,
      the naive muscle fibers gradually matured, and the number of infiltrating
      inflammatory cells decreased. Muscle ultrastructure analysis revealed that
      myocommata were correctly aligned, and the Z line was more distinct. In
      conclusion, extensive dissection of palatal muscles does not result in fibrosis.
      Injury to oral musculature can be repaired and the musculature regenerated over
      time.

PMID- 27699172
TI  - Inhibitory Effect of Long-Chain Fatty Acids on Biogas Production and the
      Protective Effect of Membrane Bioreactor.
AB  - Anaerobic digestion of lipid-containing wastes for biogas production is often
      hampered by the inhibitory effect of long-chain fatty acids (LCFAs). In this
      study, the inhibitory effects of LCFAs (palmitic, stearic, and oleic acid) on
      biogas production as well as the protective effect of a membrane bioreactor (MBR)
      against LCFAs were examined in thermophilic batch digesters. The results showed
      that palmitic and oleic acid with concentrations of 3.0 and 4.5 g/L resulted in
      >50% inhibition on the biogas production, while stearic acid had an even stronger
      inhibitory effect. The encased cells in the MBR system were able to perform
      better in the presence of LCFAs. This system exhibited a significantly lower
      percentage of inhibition than the free cell system, not reaching over 50% at any
      LCFA concentration tested.

PMID- 27699173
TI  - Experimental Models of Oral Biofilms Developed on Inert Substrates: A Review of
      the Literature.
AB  - The oral ecosystem is a very complex environment where more than 700 different
      bacterial species can be found. Most of them are organized in biofilm on dental
      and mucosal surfaces. Studying this community is important because a rupture in
      stability can lead to the preeminence of pathogenic microorganisms, causing
      dental decay, gingivitis, or periodontitis. The multitude of species complicates
      biofilm analysis so its reproduction, collection, and counting are very delicate.
      The development of experimental models of dental biofilms was therefore essential
      and multiple in vitro designs have emerged, each of them especially adapted to
      observing biofilm formation of specific bacteria within specific environments.
      The aim of this review is to analyze oral biofilm models.

PMID- 27699174
TI  - Oxygen Saturation in Closed-Globe Blunt Ocular Trauma.
AB  - Purpose. To evaluate the oxygen saturation in retinal blood vessels in patients
      after closed-globe blunt ocular trauma. Design. Retrospective observational case
      series. Methods. Retinal oximetry was performed in both eyes of 29 patients with
      unilateral closed-globe blunt ocular trauma. Arterial oxygen saturation (SaO2),
      venous oxygen saturation (SvO2), arteriovenous difference in oxygen saturation
      (SO2), arteriolar diameter, venular diameter, and arteriovenous difference in
      diameter were measured. Association parameters including age, finger pulse
      oximetry, systolic pressure, diastolic pressure, and heart rate were analyzed.
      Results. The mean SaO2 in traumatic eyes (98.1% +/- 6.8%) was not significantly
      different from SaO2 in unaffected ones (95.3% +/- 7.2%) (p = 0.136). Mean SvO2 in
      traumatic eyes (57.1% +/- 10.6%) was significantly lower than in unaffected ones
      (62.3% +/- 8.4%) (p = 0.044). The arteriovenous difference in SO2 in traumatic
      eyes (41.0% +/- 11.2%) was significantly larger than in unaffected ones (33.0% +/
      6.9%) (p = 0.002). No significant difference was observed between traumatic eyes
      and unaffected ones in arteriolar (p = 0.249) and venular diameter (p = 0.972) as
      well as arteriovenous difference in diameter (p = 0.275). Conclusions. Oxygen
      consumption is increased in eyes after cgBOT, associated with lower SvO2 and
      enlarged arteriovenous difference in SO2 but not with changes in diameter of
      retinal vessels.

PMID- 27699175
TI  - Regulation of Hepatic Stellate Cells and Fibrogenesis by Fibroblast Growth
      Factors.
AB  - Fibroblast growth factors (FGFs) are a family of growth factors critically
      involved in developmental, physiological, and pathological processes, including
      embryogenesis, angiogenesis, wound healing, and endocrine functions. In the
      liver, several FGFs are produced basally by hepatocytes and hepatic stellate
      cells (HSCs). Upon insult to the liver, expression of FGFs in HSCs is greatly
      upregulated, stimulating hepatocyte regeneration and growth. Various FGF isoforms
      have also been shown to directly induce HSC proliferation and activation thereby
      enabling autocrine and paracrine regulation of HSC function. Regulation of HSCs
      by the endocrine FGFs, namely, FGF15/19 and FGF21, has also recently been
      identified. With the ability to modulate HSC proliferation and
      transdifferentiation, targeting FGF signaling pathways constitutes a promising
      new therapeutic strategy to treat hepatic fibrosis.

PMID- 27699176
TI  - Effects of Bufei Yishen Granules Combined with Acupoint Sticking Therapy on
      Pulmonary Surfactant Proteins in Chronic Obstructive Pulmonary Disease Rats.
AB  - Our previous studies have demonstrated the beneficial effects of Bufei Yishen
      granules combined with acupoint sticking therapy (the integrated therapy) in
      chronic obstructive pulmonary disease (COPD), but the underlying mechanism
      remains unclear. Dysfunction of pulmonary surfactant proteins (SPs, including SP
      A, SP-B, SP-C, and SP-D) may be included in pathophysiology of COPD. This study
      aimed to explore the mechanism of the integrated therapy on SPs. COPD rat models
      were established. The treatment groups received Bufei Yishen granules or acupoint
      sticking or their combination. Using aminophylline as a positive control drug.
      The levels of SPs in serum, BALF, and lung were measured. The results showed that
      the integrated therapy markedly reduced the levels of SPs in serum and increased
      these indicators in the lung. The integrated therapy was better than
      aminophylline in reducing the levels of SPs and was better than Bufei Yishen
      granules in reducing SP-A, SP-C, and SP-D in serum. The integrated therapy was
      better than aminophylline and Bufei Yishen granules in increasing SP-A, SP-B, and
      SP-D mRNA in the lung. SP-A and SP-D in BALF were positively correlated with PEF
      and EF50. The levels of SPs are associated with airway limitation. The beneficial
      effects of the integrated therapy may be involved in regulating pulmonary
      surfactant proteins.

PMID- 27699177
TI  - A Facile Approach for the Mass Production of Submicro/Micro Poly (Lactic Acid)
      Fibrous Mats and Their Cytotoxicity Test towards Neural Stem Cells.
AB  - Despite many of the studies being conducted, the electrospinning of poly (lactic
      acid) (PLA), dissolved in its common solvents, is difficult to be continuously
      processed for mass production. This is due to the polymer solution droplet
      drying. Besides, the poor stretching capability of the polymer solution limits
      the production of small diameter fibers. To address these issues, we have
      examined the two following objectives: first, using an appropriate solvent system
      for the mass production of fibrous mats with fine-tunable fiber diameters;
      second, nontoxicity of the mats towards Neural Stem Cell (NSC). To this aim, TFA
      (trifluoroacetic acid) was used as a cosolvent, in a mixture with DCM
      (dichloromethane), and the solution viscosity, surface tension, electrical
      conductivity, and the continuity of the electrospinning process were compared
      with the solutions prepared with common single solvents. The binary solvent
      facilitated PLA electrospinning, resulting in a long lasting, stable
      electrospinning condition, due to the low surface tension and high conductivity
      of the binary-solvent system. The fiber diameter was tailored from nano to micro
      by varying effective parameters and examined by scanning electron microscopy
      (SEM) and image-processing software. Laminin-coated electrospun mats supported
      NSC expansion and spreading, as examined using AlamarBlue assay and fluorescent
      microscopy, respectively.

PMID- 27699179
TI  - Effects of a Patient-Provider, Collaborative, Medication-Planning Tool: A
      Randomized, Controlled Trial.
AB  - Among patients with various levels of health literacy, the effects of
      collaborative, patient-provider, medication-planning tools on outcomes relevant
      to self-management are uncertain. Objective. Among adult patients with type II
      diabetes mellitus, we tested the effectiveness of a medication-planning tool
      (MedtableTM) implemented via an electronic medical record to improve patients'
      medication knowledge, adherence, and glycemic control compared to usual care.
      Design. A multicenter, randomized controlled trial in outpatient primary care
      clinics. 674 patients received either the Medtable tool or usual care and were
      followed up for up to 12 months. Results. Patients who received Medtable had
      greater knowledge about indications for medications in their regimens and were
      more satisfied with the information about their medications. Patients' knowledge
      of drug indication improved with Medtable regardless of their literacy status.
      However, Medtable did not improve patients' demonstrated medication use, regimen
      adherence, or glycemic control (HbA1c). Conclusion. The Medtable tool supported
      provider/patient collaboration related to medication use, as reflected in patient
      satisfaction with communication, but had limited impact on patient medication
      knowledge, adherence, and HbA1c outcomes. This trial is registered with
      ClinicalTrials.gov NCT01296633.

PMID- 27699178
TI  - Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status
      and Future Perspective.
AB  - Precision medicine, a concept that has recently emerged and has been widely
      discussed, emphasizes tailoring medical care to individuals largely based on
      information acquired from molecular diagnostic testing. As a vital aspect of
      precision cancer medicine, targeted therapy has been proven to be efficacious and
      less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most
      common cancers and among the leading causes for cancer related deaths in the
      United States and worldwide. By far, CRC has been one of the most successful
      examples in the field of precision cancer medicine, applying molecular tests to
      guide targeted therapy. In this review, we summarize the current guidelines for
      anti-EGFR therapy, revisit the roles of pathologists in an era of precision
      cancer medicine, demonstrate the transition from traditional "one test-one drug"
      assays to multiplex assays, especially by using next-generation sequencing
      platforms in the clinical diagnostic laboratories, and discuss the future
      perspectives of tumor heterogeneity associated with anti-EGFR resistance and
      immune checkpoint blockage therapy in CRC.

PMID- 27699180
TI  - Altered Macrophage and Dendritic Cell Response in Mif-/- Mice Reveals a Role of
      Mif for Inflammatory-Th1 Response in Type 1 Diabetes.
AB  - Macrophage migration inhibitory factor (Mif) is highly expressed in type 1
      diabetes mellitus (T1DM). However, there is limited information about how Mif
      influences the activation of macrophages (Mphi) and dendritic cells (DC) in T1DM.
      To address this issue, we induced T1DM by administering multiple low doses of
      streptozotocin (STZ) to Mif-/- or wild-type (Wt) BALB/c mice. We found that Mif-/
      mice treated with STZ (Mif-/-STZ) developed lower levels of hyperglycemia,
      inflammatory cytokines, and specific pancreatic islet antigen- (PIAg-) IgG and
      displayed reduced cellular infiltration into the pancreatic islets compared to Wt
      mice treated with STZ (WtSTZ). Moreover, Mphi and DC from Mif-/-STZ displayed
      lower expression of MHC-II, costimulatory molecules CD80, CD86, and CD40, Toll
      like receptor- (TLR-) 2, and TLR-4 than WtSTZ. These changes were associated with
      a reduced capacity of Mphi and DC from Mif-/-STZ to induce proliferation in
      ovalbumin-specific T cells. All the deficiencies observed in Mif-/-STZ were
      recovered by exogenous administration of recombinant Mif. These findings suggest
      that Mif plays a role in the molecular mechanisms of Mphi and DC activation and
      drives T cell responses involved in the pathology of T1DM. Therefore, Mif is a
      potential therapeutic target to reduce the pathology of T1DM.

PMID- 27699183
TI  - Gram-Positive Diplococci in a Cerebrospinal Fluid Gram Stain.

PMID- 27699181
TI  - Characteristics of HLA-E Restricted T-Cell Responses and Their Role in Infectious
      Diseases.
AB  - Human HLA-E can, in addition to self-antigens, also present pathogen-derived
      sequences, which elicit specific T-cell responses. T-cells recognize their
      antigen presented by HLA-E highly specifically and have unique functional and
      phenotypical properties. Pathogen specific HLA-E restricted CD8+ T-cells are an
      interesting new player in the field of immunology. Future work should address
      their exact roles and relative contributions in the immune response against
      infectious diseases.

PMID- 27699184
TI  - Family Intervention for Obese/Overweight Children Using Portion Control Strategy
      (FOCUS) for Weight Control: A Randomized Controlled Trial.
AB  - Nutritional counseling for children with obesity is an important component of
      management. This randomized controlled trial was conducted to compare change in
      body mass index (BMI) z score after 6 months. Children 8 to 16 years with a BMI
      greater than the 85th percentile were randomized to standard of care nutrition
      counseling versus intervention with standard nutrition counseling including
      portion control tool training for the family. Measures were completed at
      baseline, 3 months, and 6 months. Fifty-one children were randomized to control
      and 48 to intervention. Mean age was 11 years (SD = 2.2). Mean BMI z score was
      2.7 (SD = 0.4). Forty-five percent were male (n = 45). Follow-up at 6 months was
      73.7% (73/99). Although no differences were seen between the groups, there was a
      significant decrease in BMI z score between baseline and 6 months within each
      group.

PMID- 27699185
TI  - Dataset of red light induced pupil constriction superimposed on post-illumination
      pupil response.
AB  - We collected and analyzed pupil diameter data from of 7 visually normal
      participants to compare the maximum pupil constriction (MPC) induced by "Red
      Only" vs. "Blue+Red" visual stimulation conditions. The "Red Only" condition
      consisted of red light (640+/-10 nm) stimuli of variable intensity and duration
      presented to dark-adapted eyes with pupils at resting state. This condition
      stimulates the cone-driven activity of the intrinsically photosensitive retinal
      ganglion cells (ipRGC). The "Blue+Red" condition consisted of the same red light
      stimulus presented during ongoing blue (470+/-17 nm) light-induced post
      illumination pupil response (PIPR), representing the cone-driven ipRGC activity
      superimposed on the melanopsin-driven intrinsic activity of the ipRGCs ("The
      Absence of Attenuating Effect of Red light Exposure on Pre-existing Melanopsin
      Driven Post-illumination Pupil Response" Lei et al. (2016) [1]). MPC induced by
      the "Red Only" condition was compared with the MPC induced by the "Blue+Red"
      condition by multiple paired sample t-tests with Bonferroni correction.

PMID- 27699182
TI  - Study of Soluble HLA-G in Congenital Human Cytomegalovirus Infection.
AB  - Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is
      expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be
      expressed as membrane-bound and soluble forms. HLA-G expression increases
      strongly during viral infections such as congenital human cytomegalovirus (HCMV)
      infections, with functional consequences in immunoregulation. In this work we
      investigated the expression of soluble (s)HLA-G and beta-2 microglobulin
      (component of HLA) molecules in correlation with the risk of transmission and
      severity of congenital HCMV infection. We analyzed 182 blood samples from 130
      pregnant women and 52 nonpregnant women and 56 amniotic fluid samples from women
      experiencing primary HCMV infection. The median levels of sHLA-G in maternal
      serum of women with primary HCMV infection were higher in comparison with
      nonprimary and uninfected pregnant women (p < 0.001). AF from HCMV symptomatic
      fetuses presented higher sHLA-G levels in comparison with infected asymptomatic
      fetuses (p < 0.001), presence of HLA-G free-heavy chain, and a concentration
      gradient from amniotic fluid to maternal blood. No significant statistical
      difference of beta-2 microglobulin median levels was observed between all
      different groups. Our results suggest the determination of sHLA-G molecules in
      both maternal blood and amniotic fluid as a promising biomarker of diagnosis of
      maternal HCMV primary infection and fetal HCMV disease.

PMID- 27699186
TI  - Data on the mixing of non-Newtonian fluids by a Rushton turbine in a cylindrical
      tank.
AB  - The paper focuses on the data collected from the mixing of shear thinning non
      Newtonian fluids in a cylindrical tank by a Rushton turbine. The data presented
      are obtained by using Computational Fluid Dynamics (CFD) simulation of fluid flow
      field in the entire tank volume. The CFD validation data for this study is
      reported in the research article 'Numerical investigation of hydrodynamic
      behavior of shear thinning fluids in stirred tank' (Khapre and Munshi, 2015) [1].
      The tracer injection method is used for the prediction of mixing time and mixing
      efficiency of a Rushton turbine impeller.

PMID- 27699187
TI  - Transcriptome data and gene ontology analysis in human macrophages ingesting
      modified lipoproteins in the presence or absence of complement protein C1q.
AB  - We characterized the transcriptional effects of complement opsonization on foam
      cell formation in human monocyte-derived macrophages (HMDM). RNA-sequencing was
      used to identify the pathways modulated by complement protein C1q during HMDM
      ingestion of the atherogenic lipoproteins oxidized low density lipoprotein
      (oxLDL) and acetylated low density lipoprotein (acLDL). All raw data were
      submitted to the MIAME-compliant database Gene Expression Omnibus (accession
      number GEO: GSE80442;
      http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80442). Data presented here
      include Venn diagram overviews of up- and down-regulated genes for each condition
      tested, gene ontology analyses of biological processes, molecular functions and
      cellular components and KEGG pathway analysis. Further investigation of the
      pathways modulated by C1q in HMDM during ingestion of atherogenic lipoproteins
      and their functional relevance are described in "Macrophage molecular signaling
      and inflammatory responses during ingestion of atherogenic lipoproteins are
      modulated by complement protein C1q" (M.M. Ho, A. Manughian-Peter, W.R. Spivia,
      A. Taylor, D.A. Fraser, 2016) [1].

PMID- 27699188
TI  - Data on industrial new orders for the euro area.
AB  - This data article provides time series on euro area industrial new orders and is
      related to the research article entitled "Modelling industrial new orders" (G.J.
      de Bondt, H.C. Dieden, S. Muzikarova, I. Vincze, 2014b) [3]. The data are in
      index format with a fixed base year (currently 2010) for total new orders as well
      as a number of breakdowns. The euro area data are based on the official national
      data for countries that still collect data and on European Central Bank (ECB)
      model estimates for countries that discontinued the data collection. The
      weighting scheme to calculate euro area aggregates makes use of country weights
      derived from industrial turnover statistics as published by Eurostat.

PMID- 27699189
TI  - Dataset of TWIST1-regulated genes in the cranial mesoderm and a transcriptome
      comparison of cranial mesoderm and cranial neural crest.
AB  - This article contains data related to the research article entitled
      "Transcriptional targets of TWIST1 in the cranial mesoderm regulate cell-matrix
      interactions and mesenchyme maintenance" by Bildsoe et al. (2016) [1]. The data
      presented here are derived from: (1) a microarray-based comparison of sorted
      cranial mesoderm (CM) and cranial neural crest (CNC) cells from E9.5 mouse
      embryos; (2) comparisons of transcription profiles of head tissues from mouse
      embryos with a CM-specific loss-of-function of Twist1 and control mouse embryos
      collected at E8.5 and E9.5; (3) ChIP-seq using a TWIST1-specific monoclonal
      antibody with chromatin extracts from TWIST1-expressing MDCK cells, a model for a
      TWIST1-dependent mesenchymal state.

PMID- 27699190
TI  - Dataset of mRNA levels for dopaminergic receptors, adrenoceptors and tyrosine
      hydroxylase in lymphocytes from subjects with clinically isolated syndromes.
AB  - This data article presents a dataset of mRNA levels for dopaminergic receptors,
      adrenoceptors and for tyrosine hydoxylase, the rate-limiting enzyme in the
      synthesis of catecholamines, in peripheral blood mononuclear cells as well as in
      CD4+ T effector and regulatory cells from subjects with clinically isolated
      syndromes (CIS), which is a first episode of neurological disturbance(s)
      suggestive of multiple sclerosis. CIS subjects are divided into two groups
      according to their eventual progression, after 12 months from CIS, to clinically
      established multiple sclerosis. The data reported are related to the article
      entitled "Dopaminergic receptors and adrenoceptors in circulating lymphocytes as
      putative biomarkers for the early onset and progression of multiple sclerosis"
      (M. Cosentino, M. Zaffaroni, M. Legnaro, R. Bombelli, L. Schembri, D. Baroncini,
      A. Bianchi, R. Clerici, M. Guidotti, P. Banfi, G. Bono, F. Marino, 2016) [1].

PMID- 27699191
TI  - Data of methylome and transcriptome derived from human dilated cardiomyopathy.
AB  - Alterations in DNA methylation and gene expression have been implicated in the
      development of human dilated cardiomyopathy (DCM). Differentially methylated
      probes (DMPs) and differentially expressed genes (DEGs) were identified between
      the left ventricle (LV, a pathological locus for DCM) and the right ventricle
      (RV, a proxy for normal hearts). The data in this DiB are for supporting our
      report entitled "Methylome analysis reveals alterations in DNA methylation in the
      regulatory regions of left ventricle development genes in human dilated
      cardiomyopathy" (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok
      Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016) [1].

PMID- 27699193
TI  - Data on the inhibition of RNase inhibitor activity by a monoclonal antibody as
      assessed by microfluidics-based RNA electrophoresis.
AB  - Using purified reaction components, a commercial monoclonal antibody (Ab)
      specific to RNase inhibitor (RI) was found to interfere with the activity of RI.
      Total RNA was mixed with a monoclonal Ab specific to either RI (clone 3F11) or
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RNase A, RI, or a combination
      of the above. Following incubation for 1 h at 22  degrees C or 37  degrees C, RNA
      integrity of the mixtures was assessed using microfluidics-based Bio-Rad Experion
      RNA electrophoresis. The addition of Ab 3F11 prevented RI from effectively
      inhibiting RNase A and therefore resulted in extensive RNA degradation. The data
      presented are associated with the research article entitled "Endogenous RNase
      Inhibitor Contributes to Stability of RNA in Crude Cell Lysates: Applicability to
      Reverse Transcription Quantitative PCR (RT-qPCR)" (Wang et al., 2016) [1].

PMID- 27699192
TI  - Data describing inhibitory profiles of sugars against hemagglutination by the
      botulinum toxin complex of Clostridium botulinum serotypes C and D.
AB  - Serotype C and D of Clostridium botulinum produce botulinum toxin complex (TC),
      which is comprised of botulinum neurotoxin, nontoxic nonhemagglutinin, and
      hemagglutinins (HAs). The TC is capable of aggregating equine erythrocytes via
      interaction between one of the HAs, namely HA-33, and sugar chains on the cell
      surface. This hemagglutination is inhibited by specific sugars. In this data
      article, we used four TCs from serotype C and D strains. The hemagglutination
      inhibiting effects of 18 sugars and 8 glycoproteins were studied. The purified TC
      was mixed with the sugar to enable binding of the sugar to the TC; then, the
      erythrocytes were added to the mixture. Specific binding between the sugar and TC
      resulted in inhibition of cell aggregation. Here, data illustrating the
      inhibitory effects of various sugars and glycoproteins against hemagglutination
      induced by TC of C. botulinum serotypes C and D are presented.

PMID- 27699194
TI  - Data on translatome analysis of Mycoplasma gallisepticum.
AB  - Mycoplasma gallisepticum is a bacterium of class Mollicutes which encompasses
      wall-less bacteria with significantly reduced genomes. Due to their overall
      reduction and simplicity mycoplasmas serve as a model of minimal cell and are
      used for systems biology studies. Here we present raw data on translatome
      (ribosome-bound mRNA) analysis of Mycoplasma gallisepticum under logarithm growth
      and heat stress. The data supports the publication of "Ribosomal profiling of
      Mycoplasma gallisepticum" (G. Y. Fisunov, D. V Evsyutina, A. A. Arzamasov, I. O.
      Butenko, V. M. Govorun, 2015) [1].

PMID- 27699195
TI  - Data on prevalence and risk factors associated with Toxocara spp infection, atopy
      and asthma development in Northeast Brazilian school children.
AB  - In the present article, we provide shortly, data on risk factors for acquiring
      Toxocara spp. infection and investigate possible associations between this
      infection with atopy and asthma in school children of a small town and its semi
      rural areas of Northeast Brazil. The data set are composed by demographic, social
      and home environment variables. The detection of anti-Toxocara spp. IgG and
      specific IgE to aeroallergens was determined by ELISA and ImmunocAP/Phadiatrope
      systems, respectively. The data presented in this article are related to the
      article entitled "Risk factors for Toxocara spp. seroprevalence and its
      association with atopy and asthma phenotypes in school-age children in a small
      town and semi-rural areas of Northeast Brazil" (M.B. Silva, A.L. Amor, L.N.
      Santos, A.A. Galvao, A.V. Oviedo Vera, E.S. Silva et al., 2016) [1].

PMID- 27699196
TI  - Data on metals (Zn, Al, Sr, and Co) and metalloid (As) concentration levels of
      ballast water in commercial ships entering Bushehr port, along the Persian Gulf.
AB  - In this article, we determined the concentration levels of metals including Zn,
      Al, Sr, and Co and metalloid of As of ballast water in commercial ships entering
      Bushehr port, along the Persian Gulf. Ballast water samples were taken from
      commercial ships entering Bushehr port from 34 ports around the world during 15
      February and 25 August 2016. The concentration levels of metals and metalloid
      were determined by using a graphite furnace absorption spectrometer (AAS).

PMID- 27699197
TI  - Data of oxygen- and pH-dependent oxidation of resveratrol.
AB  - We show here if under physiologically relevant conditions resveratrol (RSV)
      remains stable or not. We further show under which circumstances various
      oxidation products of RSV such as ROS can be produced. For example, in addition
      to the widely known effect of bicarbonate ions, high pH values promote the decay
      of RSV. Moreover, we analyse the impact of reduction of the oxygen partial
      pressure on the pH-dependent oxidation of RSV. For further interpretation and
      discussion of these focused data in a broader context we refer to the article
      "Hormetic shifting of redox environment by pro-oxidative resveratrol protects
      cells against stress" (Plauth et al., in press) [1].

PMID- 27699198
TI  - Morbility, clinical data and proteomic analysis of IUGR and AGA newborns at
      different gestational ages.
AB  - The data are related to the proteomic analysis of 43 newborns with intrauterine
      growth retardation (IUGR) and 45 newborns with appropriate weight for gestational
      age (AGA) carried out by separation via 2DE and analyzed by MS-TOF/TOF. All
      newborns were separated into three gestational age groups, "Very Preterm" 29-32
      weeks, "Moderate Preterm" 33-36 weeks, and, "Term" >=37weeks. From each newborn,
      blood was drawn three times from birth to 1 month life. High-abundant serum
      proteins were depleted, and the minority ones were separated by 2DE and analyzed
      for significant expression differences. The data reflect analytic and clinic
      variables analyzed globally and categorized by gestational age in relation to
      IUGR and the optimization of conditions for 2-DE separation. The data from this
      study are related to the research article entitled "Alterations of Protein
      Expression in Serum of Infants with Intrauterine Growth Restriction and Different
      Gestational Ages" (M.D. Ruis-Gonzalez, M.D. Canete, J.L. Gomez-Chaparro, N.
      Abril, R. Canete, J. Lopez-Barea, 2015) [1]. The present dataset of serum IUGR
      newborn proteome can be used as a reference for any study involving intrauterine
      growth restriction during the first month of life.

PMID- 27699199
TI  - Extrafacial lupus miliaris disseminatus.

PMID- 27699200
TI  - Informed decision-making about prenatal cfDNA screening: An assessment of written
      materials.
AB  - OBJECTIVES: The introduction of prenatal cfDNA screening for fetal aneuploidy and
      other genetic conditions has exacerbated concerns about informed decision-making
      in clinical prenatal testing. To assess the information provided to patients to
      facilitate decisions about cfDNA screening, we collected written patient
      education and consent documents created by laboratories and clinics. METHODS:
      Informed consent documents (IC) were coded by two independent coders. Each IC was
      assessed for readability, attention to elements of informed consent, and
      completeness of information about the test and the screened conditions. RESULTS:
      We found variance between IC produced by commercial laboratories versus those
      provided by local clinics or health care systems, and considerable variance among
      materials from all sources. "Commercial" IC were longer and written at a more
      difficult reading level than "non-commercial" IC, and were less likely to state
      explicitly that cfDNA only screens for certain conditions. About one-third of IC
      were combined with laboratory order forms. Though most IC recommended
      confirmatory testing for positive results, only about half clearly stated that
      results could be incorrect-including mentions of false positives or false
      negatives. About one-third of IC explicitly stated that cfDNA screening was
      optional. While nearly all IC from any source listed the conditions screened by
      the test, only about half of the IC included any phenotypic descriptions of these
      conditions. Few IC mentioned psychosocial considerations, and only one IC
      mentioned the availability of support groups for families of children with
      genetic conditions. CONCLUSIONS: Based on our findings, we recommend that written
      and well-informed consent be sought before performing cfDNA screening, and we
      offer minimal and recommended standards for patient education and consent
      materials.

PMID- 27699201
TI  - Restoration Effects of the Riparian Forest on the Intertidal Fish Fauna in an
      Urban Area of the Amazon River.
AB  - Urbanization causes environmental impacts that threaten the health of aquatic
      communities and alter their recovery patterns. In this study, we evaluated the
      diversity of intertidal fish in six areas affected by urbanization (areas with
      native vegetation, deforested areas, and areas in process of restoration of
      vegetation) along an urban waterfront in the Amazon River. 20 species were
      identified, representing 17 genera, 14 families, and 8 orders. The different
      degrees of habitat degradation had a major effect on the composition of the fish
      fauna; the two least affected sectors were the only ones in that all 20 species
      were found. Eight species were recorded in the most degraded areas. The analysis
      revealed two well-defined groups, coinciding with the sectors in better
      ecological quality and degraded areas, respectively. The native vegetation has
      been identified as the crucial factor to the recovery and homeostasis of the
      studied ecosystem, justifying its legal protection and its use in the restoration
      and conservation of altered and threatened environments. These results reinforce
      the importance of maintaining the native vegetation as well as its restoration in
      order to benefit of the fish populations in intertidal zones impacted by
      alterations resulting from inadequate urbanization.

PMID- 27699202
TI  - Low-Carbon Watershed Management: Potential of Greenhouse Gas Reductions from
      Wastewater Treatment in Rural Vietnam.
AB  - Currently in many cities and rural areas of Vietnam, wastewater is discharged to
      the environment without any treatment, which emits considerable amount of
      greenhouse gas (GHG), particularly methane. In this study, four GHG emission
      scenarios were examined, as well as the baseline scenario, in order to verify the
      potential of GHG reduction from domestic wastewater with adequate treatment
      facilities. The ArcGIS and ArcHydro tools were employed to visualize and analyze
      GHG emissions resulting from discharge of untreated wastewater, in rural areas of
      Vu Gia Thu Bon river basin, Vietnam. By applying the current IPCC guidelines for
      GHG emissions, we found that a reduction of GHG emissions can be achieved through
      treatment of domestic wastewater in the studied area. Compared with baseline
      scenario, a maximum 16% of total GHG emissions can be reduced, in which 30% of
      households existing latrines are substituted by Japanese Johkasou technology and
      other 20% of domestic wastewater is treated by conventional activated sludge.

PMID- 27699203
TI  - Control of Pedicle Screw Placement with an Electrical Conductivity Measurement
      Device: Initial Evaluation in the Thoracic and Lumbar Spine.
AB  - Aim. Transpedicular screw fixation is widely used in spinal surgery. But the
      insertion of pedicle screws can sometimes be challenging because of the
      variability in pedicle size and the proximity of nerve roots. Methods. We
      detected intraoperatively the sensitivity for iatrogenic pedicel perforation with
      a hand-held electronic conductivity measurement device (ECD) that measures
      electrical conductivity of tissue-medium surrounding the instrument tip. ECD was
      used to guide the placement of 84 pedicle screws in 15 patients undergoing
      surgery for tumor or degenerative spinal disease at various spinal levels from T8
      to L5. Additionally a CT-scan controlled screw positioning postoperatively.
      Results. The placement was "correct" (no mediocaudal pedicle wall penetration)
      for 78 of 84 (92,8%) screws, "suboptimal but acceptable" (0-2 mm penetration) for
      4 of 84 (4,8%) screws, and "misplaced" (penetration > 2 mm) for 2 of 84 (2,4%)
      screws. Conclusion. Although this study was not designed to compare electronic
      conductivity technique to other guidance methods, such as fluoroscopy or
      navigation, a convincing "proof of concept" for ECD use in spinal instrumentation
      could be demonstrated. Advantages include easy handling without time-consuming
      setup and reduced X-ray exposure. However, further investigations are necessary
      to evaluate i.a. the economic aspects for this single-use developed instrument.

PMID- 27699204
TI  - Role of Ultrasound in Body Stalk Anomaly and Amniotic Band Syndrome.
AB  - Body stalk anomaly (BSA) and amniotic band syndrome (ABS) are rare similar fetal
      sporadic polymalformative syndromes of unknown etiology, though there are certain
      differences between them. BSA is a combination of developmental abnormalities
      involving neural tube, body wall, and the limbs with persistent extra embryonic
      coelomic cavity. ABS is characterized by the presence of thin membrane-like
      strands attached to fetal body parts and causing constrictions and amputations.
      This is a cohort study involving 32,100 patients who were referred for routine
      antenatal ultrasound scan. The data was entered prospectively into a computer
      database. The duration of study was 3 years. In our study, ultrasound examination
      in 86 patients demonstrated ventral wall defects, craniofacial defects, and
      spinal and limb deformities as isolated or combined abnormalities. In those, 10
      patients were suspected/diagnosed as BSA/ABS including a twin of a dichorionic
      diamniotic gestation. The typical features of body stalk anomaly can be detected
      by ultrasound by the end of the first trimester, which is important for the
      patient counselling and management. We are presenting these rare conditions and
      highlighting the importance of early sonographic imaging in diagnosing and
      differentiating them from other anterior abdominal wall defects.

PMID- 27699205
TI  - Seroprevalence of Canine Parvovirus in Dogs in Lusaka District, Zambia.
AB  - Canine parvovirus (CPV) enteritis is a highly contagious enteric disease of young
      dogs. Limited studies have been done in Zambia to investigate the prevalence of
      CPV in dogs. Blood was collected from dogs from three veterinary clinics (clinic
      samples, n = 174) and one township of Lusaka (field samples, n = 56). Each dog's
      age, sex, breed, and vaccination status were recorded. A haemagglutination assay
      using pig erythrocytes and modified live parvovirus vaccine as the antigen was
      used. Antibodies to CPV were detected in 100% of dogs (unvaccinated or
      vaccinated). The titres ranged from 160 to 10240 with a median of 1280.
      Vaccinated dogs had significantly higher antibody titres compared to unvaccinated
      (p < 0.001). There was a significant difference in titres of clinic samples
      compared to field samples (p < 0.0001) but not within breed (p = 0.098) or sex (p
      = 0.572). Multiple regression analysis showed that only age and vaccination
      status were significant predictors of antibody titres. The presence of antibody
      in all dogs suggests that the CPV infection is ubiquitous and the disease is
      endemic, hence the need for research to determine the protection conferred by
      vaccination and natural exposure to the virus under local conditions.

PMID- 27699207
TI  - Slow Cholinergic Modulation of Spike Probability in Ultra-Fast Time-Coding
      Sensory Neurons.
AB  - Sensory processing in the lower auditory pathway is generally considered to be
      rigid and thus less subject to modulation than central processing. However, in
      addition to the powerful bottom-up excitation by auditory nerve fibers, the
      ventral cochlear nucleus also receives efferent cholinergic innervation from both
      auditory and nonauditory top-down sources. We thus tested the influence of
      cholinergic modulation on highly precise time-coding neurons in the cochlear
      nucleus of the Mongolian gerbil. By combining electrophysiological recordings
      with pharmacological application in vitro and in vivo, we found 55-72% of
      spherical bushy cells (SBCs) to be depolarized by carbachol on two time scales,
      ranging from hundreds of milliseconds to minutes. These effects were mediated by
      nicotinic and muscarinic acetylcholine receptors, respectively. Pharmacological
      block of muscarinic receptors hyperpolarized the resting membrane potential,
      suggesting a novel mechanism of setting the resting membrane potential for SBC.
      The cholinergic depolarization led to an increase of spike probability in SBCs
      without compromising the temporal precision of the SBC output in vitro. In vivo,
      iontophoretic application of carbachol resulted in an increase in spontaneous SBC
      activity. The inclusion of cholinergic modulation in an SBC model predicted an
      expansion of the dynamic range of sound responses and increased temporal acuity.
      Our results thus suggest of a top-down modulatory system mediated by
      acetylcholine which influences temporally precise information processing in the
      lower auditory pathway.

PMID- 27699206
TI  - Smooth versus Textured Surfaces: Feature-Based Category Selectivity in Human
      Visual Cortex.
AB  - In fMRI studies, human lateral occipital (LO) cortex is thought to respond
      selectively to images of objects, compared with nonobjects. However, it remains
      unresolved whether all objects evoke equivalent levels of activity in LO, and, if
      not, which image features produce stronger activation. Here, we used an unbiased
      parametric texture model to predict preferred versus nonpreferred stimuli in LO.
      Observation and psychophysical results showed that predicted preferred stimuli
      (both objects and nonobjects) had smooth (rather than textured) surfaces. These
      predictions were confirmed using fMRI, for objects and nonobjects. Similar
      preferences were also found in the fusiform face area (FFA). Consistent with
      this: (1) FFA and LO responded more strongly to nonfreckled (smooth) faces,
      compared with otherwise identical freckled (textured) faces; and (2) strong
      functional connections were found between LO and FFA. Thus, LO and FFA may be
      part of an information-processing stream distinguished by feature-based category
      selectivity (smooth > textured).

PMID- 27699208
TI  - The Temporal Dynamics of Scene Processing: A Multifaceted EEG Investigation.
AB  - Our remarkable ability to process complex visual scenes is supported by a network
      of scene-selective cortical regions. Despite growing knowledge about the scene
      representation in these regions, much less is known about the temporal dynamics
      with which these representations emerge. We conducted two experiments aimed at
      identifying and characterizing the earliest markers of scene-specific processing.
      In the first experiment, human participants viewed images of scenes, faces, and
      everyday objects while event-related potentials (ERPs) were recorded. We found
      that the first ERP component to evince a significantly stronger response to
      scenes than the other categories was the P2, peaking ~220 ms after stimulus
      onset. To establish that the P2 component reflects scene-specific processing, in
      the second experiment, we recorded ERPs while the participants viewed diverse
      real-world scenes spanning the following three global scene properties: spatial
      expanse (open/closed), relative distance (near/far), and naturalness (man
      made/natural). We found that P2 amplitude was sensitive to these scene properties
      at both the categorical level, distinguishing between open and closed natural
      scenes, as well as at the single-image level, reflecting both computationally
      derived scene statistics and behavioral ratings of naturalness and spatial
      expanse. Together, these results establish the P2 as an ERP marker for scene
      processing, and demonstrate that scene-specific global information is available
      in the neural response as early as 220 ms.

PMID- 27699210
TI  - Orientation Tuning Depends on Spatial Frequency in Mouse Visual Cortex.
AB  - The response properties of neurons to sensory stimuli have been used to identify
      their receptive fields and to functionally map sensory systems. In primary visual
      cortex, most neurons are selective to a particular orientation and spatial
      frequency of the visual stimulus. Using two-photon calcium imaging of neuronal
      populations from the primary visual cortex of mice, we have characterized the
      response properties of neurons to various orientations and spatial frequencies.
      Surprisingly, we found that the orientation selectivity of neurons actually
      depends on the spatial frequency of the stimulus. This dependence can be easily
      explained if one assumed spatially asymmetric Gabor-type receptive fields. We
      propose that receptive fields of neurons in layer 2/3 of visual cortex are indeed
      spatially asymmetric, and that this asymmetry could be used effectively by the
      visual system to encode natural scenes.

PMID- 27699209
TI  - Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of
      Familial Dysautonomia.
AB  - Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that
      is caused by a mutation in the gene for inhibitor of kappa B kinase complex
      associated protein (IKBKAP). Although FD patients suffer from multiple
      neuropathies, a major debilitation that affects their quality of life is
      progressive blindness. To determine the requirement for Ikbkap in the developing
      and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a
      TUBA1a promoter-Cre (Talpha1-Cre). In the retina, Talpha1-Cre expression is
      detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant
      loss of RGCs had occurred in the CKO retinas, with the greatest loss in the
      temporal retina, which is the same spatial phenotype observed in FD, Leber
      hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the
      melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of
      photoreceptor degeneration were observed, which later progressed to panretinal
      degeneration, including RGC and photoreceptor loss, optic nerve thinning, Muller
      glial activation, and disruption of layers. Taking these results together, we
      conclude that although Ikbkap is not required for normal development of RGCs, its
      loss causes a slow, progressive RGC degeneration most severely in the temporal
      retina, which is later followed by indirect photoreceptor loss and complete
      retinal disorganization. This mouse model of FD is not only useful for
      identifying the mechanisms mediating retinal degeneration, but also provides a
      model system in which to attempt to test therapeutics that may mitigate the loss
      of vision in FD patients.

PMID- 27699211
TI  - Altered Spatiotemporal Dynamics of Cortical Activation to Tactile Stimuli in
      Somatosensory Area 3b and Area 1 of Monkeys after Spinal Cord Injury.
AB  - Reactivation of deafferented cortex plays a key role in mediating the recovery of
      lost functions, although the precise mechanism is not fully understood. This
      study simultaneously characterized the dynamic spatiotemporal features of tactile
      responses in areas 3b and 1 before and 6-8 weeks after partial dorsal column
      lesion (DCL), and examined how the reactivation relates to the recovery of simple
      hand use in squirrel monkeys. A combination of high spatiotemporal resolution
      functional intrinsic optical imaging, microelectrode mapping, behavioral
      assessment, and tracer histology methods were used. Compared with the normal
      cortex, we found that the responses of deafferented areas 3b and 1 to 3 s of
      continuous 8 Hz tactile stimulation of a single digit were significantly weaker
      and more transient. This finding indicates a loss of response to sustained
      tactile stimuli. The activation area enlarged for areas 3b and 1 in both
      directions along digit representation (medial-lateral) and across areas (anterior
      posterior). All subjects showed behavioral deficits in a food reaching-grasping
      retrieving task within the first 5 weeks after DCL, but recovered at the time
      when optical images were acquired. Summarily, we showed that these populations of
      cortical neurons responded to peripheral tactile inputs, albeit in significantly
      altered manners in each area, several weeks after deafferentation. We propose
      that compromised ascending driven inputs, impaired lateral inhibition, and local
      integration of input signals may account for the altered spatiotemporal dynamics
      of the reactivated areas 3b and 1 cortices. Further investigation with large
      sample sizes is needed to fully characterize the effects of deafferentation on
      area 1 activation size.

PMID- 27699212
TI  - Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic
      Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased
      Motor Activity and Decreased Sugar Consumption.
AB  - The subthalamic nucleus (STN) plays a central role in motor, cognitive, and
      affective behavior. Deep brain stimulation (DBS) of the STN is the most common
      surgical intervention for advanced Parkinson's disease (PD), and STN has lately
      gained attention as target for DBS in neuropsychiatric disorders, including
      obsessive compulsive disorder, eating disorders, and addiction. Animal studies
      using STN-DBS, lesioning, or inactivation of STN neurons have been used
      extensively alongside clinical studies to unravel the structural organization,
      circuitry, and function of the STN. Recent studies in rodent STN models have
      exposed different roles for STN neurons in reward-related functions. We have
      previously shown that the majority of STN neurons express the vesicular glutamate
      transporter 2 gene (Vglut2/Slc17a6) and that reduction of Vglut2 mRNA levels
      within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic
      activity and behavioral hyperlocomotion. The cKO mice showed less interest in
      fatty rewards, which motivated analysis of reward-response. The current results
      demonstrate decreased sugar consumption and strong rearing behavior, whereas
      biochemical analyses show altered dopaminergic and peptidergic activity in the
      striatum. The behavioral alterations were in fact correlated with opposite
      effects in the dorsal versus the ventral striatum. Significant cell loss and
      disorganization of the STN structure was identified, which likely accounts for
      the observed alterations. Rare genetic variants of the human VGLUT2 gene exist,
      and this study shows that reduced Vglut2/Slc17a6 gene expression levels
      exclusively within the STN of mice is sufficient to cause strong modifications in
      both the STN and the mesostriatal dopamine system.

PMID- 27699215
TI  - Our inaugural issue.
AB  - We are delighted to publish the first set of articles in JCI Insight, the newest
      peer-reviewed publication of the American Society for Clinical Investigation
      (ASCI), a nonprofit honor society for physician-scientists. In creating this
      journal, we sought to provide an expanded forum for a wide range of preclinical,
      translational, and clinical research that uncovers new insights into the basis of
      disease and therapeutic approaches. In selecting articles for JCI Insight, we
      place a strong emphasis on rigorous experimental methods and data reporting,
      which are truly the hallmark of publications in the JCI family. Like the research
      in the Journal of Clinical Investigation, all articles in JCI Insight are freely
      available from the moment of publication. ASCI is proud to continue this
      tradition of open access, which we believe to be a cornerstone of the
      dissemination of scientific findings.

PMID- 27699213
TI  - Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis.
AB  - Renal tubular atrophy and interstitial fibrosis are common hallmarks of
      etiologically different progressive chronic kidney diseases (CKD) that eventually
      result in organ failure. Even though these pathological manifestations constitute
      a major public health problem, diagnostic tests, as well as therapeutic options,
      are currently limited. Members of the dickkopf (DKK) family, DKK1 and -2, have
      been associated with inhibition of Wnt signaling and organ fibrosis. Here, we
      identify DKK3 as a stress-induced, tubular epithelia-derived, secreted
      glycoprotein that mediates kidney fibrosis. Genetic as well as antibody-mediated
      abrogation of DKK3 led to reduced tubular atrophy and decreased interstitial
      matrix accumulation in two mouse models of renal fibrosis. This was facilitated
      by an amplified, antifibrogenic, inflammatory T cell response and diminished
      canonical Wnt/beta-catenin signaling in stressed tubular epithelial cells.
      Moreover, in humans, urinary DKK3 levels specifically correlated with the extent
      of tubular atrophy and interstitial fibrosis in different glomerular and
      tubulointerstitial diseases. In summary, our data suggest that DKK3 constitutes
      an immunosuppressive and a profibrotic epithelial protein that might serve as a
      potential therapeutic target and diagnostic marker in renal fibrosis.

PMID- 27699216
TI  - Deep sequencing reveals microRNAs predictive of antiangiogenic drug response.
AB  - The majority of metastatic renal cell carcinoma (RCC) patients are treated with
      tyrosine kinase inhibitors (TKI) in first-line treatment; however, a fraction are
      refractory to these antiangiogenic drugs. MicroRNAs (miRNAs) are regulatory
      molecules proven to be accurate biomarkers in cancer. Here, we identified miRNAs
      predictive of progressive disease under TKI treatment through deep sequencing of
      74 metastatic clear cell RCC cases uniformly treated with these drugs. Twenty
      nine miRNAs were differentially expressed in the tumors of patients who
      progressed under TKI therapy (P values from 6 * 10-9 to 3 * 10-3). Among 6 miRNAs
      selected for validation in an independent series, the most relevant associations
      corresponded to miR-1307-3p, miR-155-5p, and miR-221-3p (P = 4.6 * 10-3, 6.5 * 10
      3, and 3.4 * 10-2, respectively). Furthermore, a 2 miRNA-based classifier
      discriminated individuals with progressive disease upon TKI treatment (AUC =
      0.75, 95% CI, 0.64-0.85; P = 1.3 * 10-4) with better predictive value than
      clinicopathological risk factors commonly used. We also identified miRNAs
      significantly associated with progression-free survival and overall survival (P =
      6.8 * 10-8 and 7.8 * 10-7 for top hits, respectively), and 7 overlapped with
      early progressive disease. In conclusion, this is the first miRNome comprehensive
      study, to our knowledge, that demonstrates a predictive value of miRNAs for TKI
      response and provides a new set of relevant markers that can help rationalize
      metastatic RCC treatment.

PMID- 27699214
TI  - Relationships among injury, fibrosis, and time in human kidney transplants.
AB  - BACKGROUND: Kidney transplant biopsies offer an opportunity to understand the
      pathogenesis of organ fibrosis. We studied the relationships between the time of
      biopsy after transplant (TxBx), histologic fibrosis, diseases, and transcript
      expression. METHODS: Expression microarrays from 681 kidney transplant indication
      biopsies taken either early (n = 282, <1 year) or late (n = 399, >1 year) after
      transplant were used to analyze the molecular landscape of fibrosis in
      relationship to histologic fibrosis and diseases. RESULTS: Fibrosis was absent at
      transplantation but was present in some early biopsies by 4 months after
      transplant, apparently as a self-limited response to donation implantation injury
      not associated with progression to failure. The molecular phenotype of early
      biopsies represented the time sequence of the response to wounding: immediate
      expression of acute kidney injury transcripts, followed by fibrillar collagen
      transcripts after several weeks, then by the appearance of immunoglobulin and
      mast cell transcripts after several months as fibrosis appeared. Fibrosis in late
      biopsies correlated with injury, fibrillar collagen, immunoglobulin, and mast
      cell transcripts, but these were independent of time. Pathway analysis revealed
      epithelial response-to-wounding pathways such as Wnt/beta-catenin. CONCLUSION:
      Fibrosis in late biopsies had different associations because many kidneys had
      potentially progressive diseases and subsequently failed. Molecular correlations
      with fibrosis in late biopsies were independent of time, probably because ongoing
      injury obscured the response-to-wounding time sequence. The results indicate that
      fibrosis in kidney transplants is driven by nephron injury and that progression
      to failure reflects continuing injury, not autonomous fibrogenesis. TRIAL
      REGISTRATION: INTERCOM study (www.clinicalTrials.gov; NCT01299168). FUNDING:
      Canada Foundation for Innovation and Genome Canada.

PMID- 27699217
TI  - Perinatal tolerance to proinsulin is sufficient to prevent autoimmune diabetes.
AB  - High-affinity self-reactive thymocytes are purged in the thymus, and residual
      self-reactive T cells, which are detectable in healthy subjects, are controlled
      by peripheral tolerance mechanisms. Breakdown in these mechanisms results in
      autoimmune disease, but antigen-specific therapy to augment natural mechanisms
      can prevent this. We aimed to determine when antigen-specific therapy is most
      effective. Islet autoantigens, proinsulin (PI), and islet-specific glucose-6
      phosphatase catalytic subunit-related protein (IGRP) were expressed in the
      antigen-presenting cells (APCs) of autoimmune diabetes-prone nonobese diabetic
      (NOD) mice in a temporally controlled manner. PI expression from gestation until
      weaning was sufficient to completely protect NOD mice from diabetes, insulitis,
      and development of insulin autoantibodies. Insulin-specific T cells were
      significantly diminished, were naive, and did not express IFN-gamma when
      challenged. This long-lasting effect from a brief period of treatment suggests
      that autoreactive T cells are not produced subsequently. We tracked IGRP206-214
      specific CD8+ T cells in NOD mice expressing IGRP in APCs. When IGRP was
      expressed only until weaning, IGRP206-214-specific CD8+ T cells were not detected
      later in life. Thus, anti-islet autoimmunity is determined during early life, and
      autoreactive T cells are not generated in later life. Bolstering tolerance to
      islet antigens in the perinatal period is sufficient to impart lasting protection
      from diabetes.

PMID- 27699218
TI  - The MEK inhibitor trametinib separates murine graft-versus-host disease from
      graft-versus-tumor effects.
AB  - The efficacy of allogeneic hematopoietic stem cell transplantation for
      hematologic malignancies is limited by the difficulty in suppressing graft-versus
      host disease (GVHD) without compromising graft-versus-tumor (GVT) effects. We
      previously showed that RAS/MEK/ERK signaling depends on memory differentiation in
      human T cells, which confers susceptibility to selective inhibition of naive T
      cells. Actually, antineoplastic MEK inhibitors selectively suppress alloreactive
      T cells, sparing virus-specific T cells in vitro. Here, we show that trametinib,
      a MEK inhibitor clinically approved for melanoma, suppresses GVHD safely without
      affecting GVT effects in vivo. Trametinib prolonged survival of GVHD mice and
      attenuated GVHD symptoms and pathology in the gut and skin. It inhibited ERK1/2
      phosphorylation and expansion of donor T cells, sparing Tregs and B cells.
      Although high-dose trametinib inhibited myeloid cell engraftment, low-dose
      trametinib suppressed GVHD without severe adverse events. Notably, trametinib
      facilitated the survival of mice transplanted with allogeneic T cells and P815
      tumor cells with no residual P815 cells observed in the livers and spleens,
      whereas tacrolimus resulted in P815 expansion. These results confirm that
      trametinib selectively suppresses GVHD-inducing T cells while sparing antitumor T
      cells in vivo, which makes it a promising candidate for translational studies
      aimed at preventing or treating GVHD.

PMID- 27699220
TI  - Biofilm in group A streptococcal necrotizing soft tissue infections.
AB  - Necrotizing fasciitis caused by group A streptococcus (GAS) is a life
      threatening, rapidly progressing infection. At present, biofilm is not recognized
      as a potential problem in GAS necrotizing soft tissue infections (NSTI), as it is
      typically linked to chronic infections or associated with foreign devices. Here,
      we present a case of a previously healthy male presenting with NSTI caused by
      GAS. The infection persisted over 24 days, and the surgeon documented the
      presence of a "thick layer biofilm" in the fascia. Subsequent analysis of NSTI
      patient tissue biopsies prospectively included in a multicenter study revealed
      multiple areas of biofilm in 32% of the patients studied. Biopsies associated
      with biofilm formation were characterized by massive bacterial load, a pronounced
      inflammatory response, and clinical signs of more severe tissue involvement. In
      vitro infections of a human skin tissue model with GAS NSTI isolates also
      revealed multilayered fibrous biofilm structures, which were found to be under
      the control of the global Nra gene regulator. The finding of GAS biofilm
      formation in NSTIs emphasizes the urgent need for biofilm to be considered as a
      potential complicating microbiological feature of GAS NSTI and, consequently,
      emphasizes reconsideration of antibiotic treatment protocols.

PMID- 27699219
TI  - Profiling cancer testis antigens in non-small-cell lung cancer.
AB  - Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present
      valuable targets for immunotherapy. To comprehensively characterize the CTA
      landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199
      NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal
      organs. Of 232 CTAs currently annotated in the Caner Testis Database
      (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of
      NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes
      as CTAs, of which 55 genes were not annotated in the CTdatabase, thus
      representing potential new CTAs. Cluster analysis revealed that CTA expression is
      histology dependent and concurrent expression is common. IHC confirmed tissue
      specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and
      CXORF67). Furthermore, methylation was identified as a regulatory mechanism of
      CTA expression based on independent data from The Cancer Genome Atlas. The
      proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in
      our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In
      summary, we defined a set of 90 reliable CTAs, including information on protein
      expression, methylation, and survival association. The detailed RNAseq catalog
      can guide biomarker studies and efforts to identify targets for immunotherapeutic
      strategies.

PMID- 27699221
TI  - Soluble membrane attack complex is diagnostic for intraventricular shunt
      infection in children.
AB  - BACKGROUND: Children treated with cerebrospinal fluid (CSF) shunts to manage
      hydrocephalus frequently develop shunt failure and/or infections, conditions that
      present with overlapping symptoms. The potential life-threatening nature of shunt
      infections requires rapid diagnosis; however, traditional microbiology is time
      consuming, expensive, and potentially unreliable. We set out to identify a
      biomarker that would identify shunt infection. METHODS: CSF was assayed for the
      soluble membrane attack complex (sMAC) by ELISA in patients with suspected shunt
      failure or infection. CSF was obtained at the time of initial surgical
      intervention. Statistical analysis was performed to assess the diagnostic
      potential of sMAC in pyogenic-infected versus noninfected patients. RESULTS:
      Children with pyogenic shunt infection had significantly increased sMAC levels
      compared with noninfected patients (3,211 +/- 1,111 ng/ml vs. 26 +/- 3.8 ng/ml, P
      = 0.0001). In infected patients undergoing serial CSF draws, sMAC levels were
      prognostic for both positive and negative clinical outcomes. Children with
      delayed, broth-only growth of commensal organisms (P. acnes, S. epidermidis,
      etc.) had the lowest sMAC levels (7.96 +/- 1.7 ng/ml), suggesting contamination
      rather than shunt infection. CONCLUSION: Elevated CSF sMAC levels are both
      sensitive and specific for diagnosing pyogenic shunt infection and may serve as a
      useful prognostic biomarker during recovery from infection. FUNDING: This work
      was supported in part by the Impact Fund of Children's of Alabama.

PMID- 27699222
TI  - Maternal obesity drives functional alterations in uterine NK cells.
AB  - Over one-fifth of North American women of childbearing age are obese, putting
      these women at risk for a variety of detrimental chronic diseases. In addition,
      obesity increases the risk for developing major complications during pregnancy.
      The mechanisms by which obesity contributes to pregnancy complications and loss
      remain unknown. Increasing evidence indicates that obesity results in major
      changes to adipose tissue immune cell composition and function; whether or not
      obesity also affects immune function in the uterus has not been explored. Here we
      investigated the effect of obesity on uterine natural killer (uNK) cells, which
      are essential for uterine artery remodeling and placental development. Using a
      cohort of obese or lean women, we found that obesity led to a significant
      reduction in uNK cell numbers accompanied with impaired uterine artery
      remodeling. uNK cells isolated from obese women had altered expression of genes
      and pathways associated with extracellular matrix remodeling and growth factor
      signaling. Specifically, uNK cells were hyper-responsive to PDGF, resulting in
      overexpression of decorin. Functionally, decorin strongly inhibited placental
      development by limiting trophoblast survival. Together, these findings establish
      a potentially new link between obesity and poor pregnancy outcomes, and indicate
      that obesity-driven changes to uterine-resident immune cells critically impair
      placental development.

PMID- 27699223
TI  - Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the
      kidney.
AB  - Acute kidney injury (AKI) is a common clinical condition defined as a rapid
      decline in kidney function. AKI is a global health burden, estimated to cause 2
      million deaths annually worldwide. Unlike AKI in the young, which is reversible,
      AKI in the elderly often leads to end-stage renal disease, and the mechanism that
      prevents kidney repair in the elderly is unclear. Here we demonstrate that aged
      but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the
      kidney after AKI. TLT size was associated with impaired renal function and
      increased expression of proinflammatory cytokines and homeostatic chemokines,
      indicating a possible contribution of TLTs to sustained inflammation after
      injury. Notably, resident fibroblasts from a single lineage diversified into p75
      neurotrophin receptor+ (p75NTR+) fibroblasts and homeostatic chemokine-producing
      fibroblasts inside TLTs, and retinoic acid-producing fibroblasts around TLTs.
      Deletion of CD4+ cells as well as late administration of dexamethasone abolished
      TLTs and improved renal outcomes. Importantly, aged but not young human kidneys
      also formed TLTs that had cellular and molecular components similar to those of
      mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel
      therapeutic strategy for AKI in the elderly.

PMID- 27699224
TI  - Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy.
AB  - The autosomal recessive neuromuscular disease spinal muscular atrophy (SMA) is
      caused by loss of survival motor neuron (SMN) protein. Molecular pathways that
      are disrupted downstream of SMN therefore represent potentially attractive
      therapeutic targets for SMA. Here, we demonstrate that therapeutic targeting of
      ubiquitin pathways disrupted as a consequence of SMN depletion, by increasing
      levels of one key ubiquitination enzyme (ubiquitin-like modifier activating
      enzyme 1 [UBA1]), represents a viable approach for treating SMA. Loss of UBA1 was
      a conserved response across mouse and zebrafish models of SMA as well as in
      patient induced pluripotent stem cell-derive motor neurons. Restoration of UBA1
      was sufficient to rescue motor axon pathology and restore motor performance in
      SMA zebrafish. Adeno-associated virus serotype 9-UBA1 (AAV9-UBA1) gene therapy
      delivered systemic increases in UBA1 protein levels that were well tolerated over
      a prolonged period in healthy control mice. Systemic restoration of UBA1 in SMA
      mice ameliorated weight loss, increased survival and motor performance, and
      improved neuromuscular and organ pathology. AAV9-UBA1 therapy was also sufficient
      to reverse the widespread molecular perturbations in ubiquitin homeostasis that
      occur during SMA. We conclude that UBA1 represents a safe and effective
      therapeutic target for the treatment of both neuromuscular and systemic aspects
      of SMA.

PMID- 27699225
TI  - Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet
      cartilage degeneration.
AB  - Osteoarthritis (OA) of spine (facet joints [FJs]) is one of the major causes of
      severe low back pain and disability worldwide. The degeneration of facet
      cartilage is a hallmark of FJ OA. However, endogenous mechanisms that initiate
      degeneration of facet cartilage are unknown, and there are no disease-modifying
      therapies to stop FJ OA. In this study, we have identified microRNAs (small
      noncoding RNAs) as mediators of FJ cartilage degeneration. We first established a
      cohort of patients with varying degrees of facet cartilage degeneration (control
      group: normal or mild facet cartilage degeneration; FJ OA group: moderate to
      severe facet cartilage degeneration) and then screened 2,100 miRNAs and
      identified 2 miRNAs (miR-181a-5p and miR-4454) that were significantly elevated
      in FJ OA cartilage compared with control facet cartilage. We further explored
      their role, function, and signaling mechanisms using computational, in vitro
      functional, and in vivo studies. We specifically indicate that miR-181a-5p and
      miR-4454 are involved in promoting inflammatory, catabolic, and cell death
      activity in FJ chondrocytes. This is the first report to our knowledge that
      identifies miR-181a-5p and miR-4454 as mediators of cartilage degeneration in FJs
      and potential therapeutic targets for stopping cartilage degeneration.

PMID- 27699226
TI  - Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse
      ocular scarring.
AB  - Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly
      causing blindness, for which there is no antifibrotic therapy. Aldehyde
      dehydrogenase family 1 (ALDH1) is upregulated in both ocular MMP (OMMP)
      conjunctiva and cultured fibroblasts. Application of the ALDH metabolite,
      retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a
      diseased phenotype. Conversely, application of ALDH inhibitors, including
      disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of
      normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of
      scarring allergic eye disease (AED), used here as a surrogate for OMMP, in which
      topical application of disulfiram decreased fibrosis in vivo. These data suggest
      that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation,
      that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal
      scarring, and that ALDH inhibition with disulfiram is a potential and readily
      translatable antifibrotic therapy.

PMID- 27699227
TI  - Elimination of p19ARF-expressing cells enhances pulmonary function in mice.
AB  - Senescent cells accumulate in many tissues as animals age and are considered to
      underlie several aging-associated pathologies. The tumor suppressors p19ARF and
      p16INK4a, both of which are encoded in the CDKN2A locus, play critical roles in
      inducing and maintaining permanent cell cycle arrest during cellular senescence.
      Although the elimination of p16INK4a-expressing cells extends the life span of
      the mouse, it is unclear whether tissue function is restored by the elimination
      of senescent cells in aged animals and whether and how p19ARF contributes to
      tissue aging. The aging-associated decline in lung function is characterized by
      an increase in compliance as well as pathogenic susceptibility to pulmonary
      diseases. We herein demonstrated that pulmonary function in 12-month-old mice was
      reversibly restored by the elimination of p19ARF-expressing cells. The ablation
      of p19ARF-expressing cells using a toxin receptor-mediated cell knockout system
      ameliorated aging-associated lung hypofunction. Furthermore, the aging-associated
      gene expression profile was reversed after the elimination of p19ARF. Our results
      indicate that the aging-associated decline in lung function was, at least partly,
      attributed to p19ARF and was recovered by eliminating p19ARF-expressing cells.

PMID- 27699228
TI  - Decreases in thymopoiesis of astronauts returning from space flight.
AB  - Following the advent of molecular assays that measure T cell receptor excision
      circles (TRECs) present in recent thymic emigrants, it has been conclusively
      shown that thymopoiesis persists in most adults, but that functional output
      decreases with age, influencing the maintenance of a diverse and functional T
      cell receptor (TCR) repertoire. Space flight has been shown to result in a
      variety of phenotypic and functional changes in human T cells and in the
      reactivation of latent viruses. While space flight has been shown to influence
      thymic architecture in rodents, thymopoiesis has not previously been assessed in
      astronauts. Here, we assessed thymopoiesis longitudinally over a 1-year period
      prior to and after long-term space flight (median duration, 184 days) in 16
      astronauts. While preflight assessments of thymopoiesis remained quite stable in
      individual astronauts, we detected significant suppression of thymopoiesis in all
      subjects upon return from space flight. We also found significant increases in
      urine and plasma levels of endogenous glucocorticoids coincident with the
      suppression of thymopoiesis. The glucocorticoid induction and thymopoiesis
      suppression were transient, and they normalized shortly after return to Earth.
      This is the first report to our knowledge to prospectively demonstrate a
      significant change in thymopoiesis in healthy individuals in association with a
      defined physiologic emotional and physical stress event. These results suggest
      that suppression of thymopoiesis has the potential to influence the maintenance
      of the TCR repertoire during extended space travel. Further studies of
      thymopoiesis and endogenous glucocorticoids in other stress states, including
      illness, are warranted.

PMID- 27699229
TI  - Quantum coherence spectroscopy to measure dietary fat retention in the liver.
AB  - The prevalence of fatty liver reaches alarming proportions. Fatty liver increases
      the risk for insulin resistance, cardiovascular disease, and nonalcoholic
      steatohepatitis (NASH). Although extensively studied in a preclinical setting,
      the lack of noninvasive methodologies hampers our understanding of which pathways
      promote hepatic fat accumulation in humans. Dietary fat retention is one of the
      pathways that may lead to fatty liver. The low (1.1%) natural abundance (NA) of
      carbon-13 (13C) allows use of 13C-enriched lipids for in vivo MR studies.
      Successful implementation of such methodology, however, is challenging due to low
      sensitivity of 13C-magnetic resonance spectroscopy (13C-MRS). Here, we
      investigated the use of 1-dimensional gradient enhanced heteronuclear single
      quantum coherence (ge-HSQC) spectroscopy for the in vivo detection of hepatic 1H
      [13C]-lipid signals after a single high-fat meal with 13C-labeled fatty acids in
      5 lean and 6 obese subjects. Postprandial retention of orally administered 13C
      labeled fatty acids was significant (P < 0.01). Approximately 1.5% of the tracer
      was retained in the liver after 6 hours, and retention was similar in both groups
      (P = 0.92). Thus, a substantial part of the liver fat can originate directly from
      storage of meal-derived fat. The ge-HSQC can be used to noninvasively reveal the
      contribution of dietary fat to the development of hepatic steatosis over time.

PMID- 27699230
TI  - A cord blood monocyte-derived cell therapy product accelerates brain
      remyelination.
AB  - Microglia and monocytes play important roles in regulating brain remyelination.
      We developed DUOC-01, a cell therapy product intended for treatment of
      demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear
      cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are
      derived from CB CD14+ monocytes. We compared the ability of freshly isolated CB
      CD14+ monocytes and DUOC-01 cells to accelerate remyelination of the brains of
      NOD/SCID/IL2Rgammanull mice following cuprizone feeding-mediated demyelination.
      The corpus callosum of mice intracranially injected with DUOC-01 showed enhanced
      myelination, a higher proportion of fully myelinated axons, decreased gliosis and
      cellular infiltration, and more proliferating oligodendrocyte lineage cells than
      those of mice receiving excipient. Uncultured CB CD14+ monocytes also accelerated
      remyelination, but to a significantly lesser extent than DUOC-01 cells.
      Microarray analysis, quantitative PCR studies, Western blotting, and flow
      cytometry demonstrated that expression of factors that promote remyelination
      including PDGF-AA, stem cell factor, IGF1, MMP9, MMP12, and triggering receptor
      expressed on myeloid cells 2 were upregulated in DUOC-01 compared to CB CD14+
      monocytes. Collectively, our results show that DUOC-01 accelerates brain
      remyelination by multiple mechanisms and could be beneficial in treating
      demyelinating conditions.

PMID- 27699231
TI  - Gene pathway development in human epicardial adipose tissue during early life.
AB  - Studies in rodents and newborn humans demonstrate the influence of brown adipose
      tissue (BAT) in temperature control and energy balance and a critical role in the
      regulation of body weight. Here, we obtained samples of epicardial adipose tissue
      (EAT) from neonates, infants, and children in order to evaluate changes in their
      transcriptional landscape by applying a systems biology approach. Surprisingly,
      these analyses revealed that the transition to infancy is a critical stage for
      changes in the morphology of EAT and is reflected in unique gene expression
      patterns of a substantial proportion of thermogenic gene transcripts (~10%). Our
      results also indicated that the pattern of gene expression represents a distinct
      developmental stage, even after the rebound in abundance of thermogenic genes in
      later childhood. Using weighted gene coexpression network analyses, we found
      precise anthropometric-specific correlations with changes in gene expression and
      the decline of thermogenic capacity within EAT. In addition, these results
      indicate a sequential order of transcriptional events affecting cellular
      pathways, which could potentially explain the variation in the amount, or
      activity, of BAT in adulthood. Together, these results provide a resource to
      elucidate gene regulatory mechanisms underlying the progressive development of
      BAT during early life.

PMID- 27699233
TI  - T cell responses to human platelet antigen-1a involve a unique form of indirect
      allorecognition.
AB  - Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a pregnancy-related
      condition caused by maternal antibodies binding an alloantigen on fetal
      platelets. In most cases the alloantigen is formed by a single amino acid,
      integrin beta3 Leu33, referred to as human platelet antigen-1a (HPA-1a).
      Production of anti-HPA-1a antibodies likely depends on CD4+ T cells that
      recognize the same alloantigen in complex with the HLA-DRA/DRB3*01:01 molecule.
      While this complex is well characterized, T cell recognition of it is not. Here,
      to examine the nature of antigen recognition by HPA-1a-specific T cells, we
      assayed native and synthetic variants of the integrin beta3 peptide antigen for
      binding to DRA/DRB3*01:01-positive antigen-presenting cells and for T cell
      activation. We found that HPA-1a-specific T cells recognize non-allogeneic
      integrin beta3 residues anchored to DRA/DRB3*01:01 by the allogeneic Leu33, which
      itself is not directly recognized by these T cells. Furthermore, these T cell
      responses are diverse, with different T cells depending on different residues for
      recognition. This represents a unique form of indirect allorecognition in which a
      non-allogeneic peptide sequence becomes immunogenic by stable anchoring to MHC by
      an allogeneic residue.

PMID- 27699232
TI  - The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug
      resistance in a mouse model of chronic tuberculosis.
AB  - Pirfenidone is a recently approved antifibrotic drug for the treatment of
      idiopathic pulmonary fibrosis (IPF). Because tuberculosis (TB) is characterized
      by granulomatous inflammation in conjunction with parenchymal destruction and
      replacement fibrosis, we sought to determine whether the addition of pirfenidone
      as an adjunctive, host-directed therapy provides a beneficial effect during
      antimicrobial treatment of TB. We hypothesized that pirfenidone's
      antiinflammatory and antifibrotic properties would reduce inflammatory lung
      damage and increase antimicrobial drug penetration in granulomas to accelerate
      treatment response. The effectiveness of adjunctive pirfenidone during TB drug
      therapy was evaluated using a murine model of chronic TB. Mice treated with
      standard therapy 2HRZ/4HR (H, isoniazid; R, rifampin; and Z, pyrazinamide) were
      compared with 2 alternative regimens containing pirfenidone (Pf) (2HRZPf/4HRPf
      and 2HRZPf/4HR). Contrary to our hypothesis, adjunctive pirfenidone use leads to
      reduced bacterial clearance and increased relapse rates. This treatment failure
      is closely associated with the emergence of isoniazid monoresistant bacilli,
      increased cavitation, and significant lung pathology. While antifibrotic agents
      may eventually be used as part of adjunctive host-directed therapy of TB, this
      study clearly demonstrates that caution must be exercised. Moreover, as
      pirfenidone becomes more widely used in clinical practice, increased patient
      monitoring would be required in endemic TB settings.

PMID- 27699234
TI  - Telomere dysfunction in alveolar epithelial cells causes lung remodeling and
      fibrosis.
AB  - Telomeres are short in type II alveolar epithelial cells (AECs) of patients with
      idiopathic pulmonary fibrosis (IPF). Whether dysfunctional telomeres contribute
      directly to development of lung fibrosis remains unknown. The objective of this
      study was to investigate whether telomere dysfunction in type II AECs, mediated
      by deletion of the telomere shelterin protein TRF1, leads to pulmonary fibrosis
      in mice (SPC-Cre TRF1fl/fl mice). Deletion of TRF1 in type II AECs for 2 weeks
      increased gammaH2AX DNA damage foci, but not histopathologic changes in the lung.
      Deletion of TRF1 in type II AECs for up to 9 months resulted in short telomeres
      and lung remodeling characterized by increased numbers of type II AECs, alpha
      smooth muscle actin+ mesenchymal cells, collagen deposition, and accumulation of
      senescence-associated beta-galactosidase+ lung epithelial cells. Deletion of TRF1
      in collagen-expressing cells caused pulmonary edema, but not fibrosis. These
      results demonstrate that prolonged telomere dysfunction in type II AECs, but not
      collagen-expressing cells, leads to age-dependent lung remodeling and fibrosis.
      We conclude that telomere dysfunction in type II AECs is sufficient to cause lung
      fibrosis, and may be a dominant molecular defect causing IPF. SPC-Cre TRF1fl/fl
      mice will be useful for assessing cellular and molecular mechanisms of lung
      fibrosis mediated by telomere dysfunction.

PMID- 27699235
TI  - IL1RL1 asthma risk variants regulate airway type 2 inflammation.
AB  - Genome-wide association studies of asthma have identified genetic variants in the
      IL1RL1 gene, but the molecular mechanisms conferring risk are unknown. IL1RL1
      encodes the ST2 receptor (ST2L) for IL-33 and an inhibitory decoy receptor
      (sST2). IL-33 promotes type 2 inflammation, which is present in some but not all
      asthmatics. We find that two single nucleotide polymorphisms (SNPs) in IL1RL1 -
      rs1420101 and rs11685480 - are strongly associated with plasma sST2 levels,
      though neither is an expression quantitative trait locus (eQTL) in whole blood.
      Rather, rs1420101 and rs11685480 mark eQTLs in airway epithelial cells and distal
      lung parenchyma, respectively. We find that the genetically determined plasma
      sST2 reservoir, derived from the lung, neutralizes IL-33 activity, and these eQTL
      SNPs additively increase the risk of airway type 2 inflammation among asthmatics.
      These risk variants define a population of asthmatics at risk of IL-33-driven
      type 2 inflammation.

PMID- 27699236
TI  - Glymphatic fluid transport controls paravascular clearance of AAV vectors from
      the brain.
AB  - Adeno-associated viruses (AAV) are currently being evaluated in clinical trials
      for gene therapy of CNS disorders. However, host factors that influence the
      spread, clearance, and transduction efficiency of AAV vectors in the brain are
      not well understood. Recent studies have demonstrated that fluid flow mediated by
      aquaporin-4 (AQP4) channels located on astroglial end feet is essential for
      exchange of solutes between interstitial and cerebrospinal fluid. This
      phenomenon, which is essential for interstitial clearance of solutes from the
      CNS, has been termed glial-associated lymphatic transport or glymphatic
      transport. In the current study, we demonstrate that glymphatic transport
      profoundly affects various aspects of AAV gene transfer in the CNS. Altered
      localization of AQP4 in aged mouse brains correlated with significantly increased
      retention of AAV vectors in the parenchyma and reduced systemic leakage following
      ventricular administration. We observed a similar increase in AAV retention and
      transgene expression upon i.c.v. administration in AQP4-/- mice. Consistent with
      this observation, fluorophore-labeled AAV vectors showed markedly reduced flux
      from the ventricles of AQP4-/- mice compared with WT mice. These results were
      further corroborated by reduced AAV clearance from the AQP4-null brain, as
      demonstrated by reduced transgene expression and vector genome accumulation in
      systemic organs. We postulate that deregulation of glymphatic transport in aged
      and diseased brains could markedly affect the parenchymal spread, clearance, and
      gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the
      kinetics of CSF flux in prospective gene therapy patients might inform variable
      treatment outcomes and guide future clinical trial design.

PMID- 27699237
TI  - Platelet integrin alpha6beta1 controls lung metastasis through direct binding to
      cancer cell-derived ADAM9.
AB  - Metastatic dissemination of cancer cells, which accounts for 90% of cancer
      mortality, is the ultimate hallmark of malignancy. Growing evidence suggests that
      blood platelets have a predominant role in tumor metastasis; however, the
      molecular mechanisms involved remain elusive. Here, we demonstrate that genetic
      deficiency of integrin alpha6beta1 on platelets markedly decreases experimental
      and spontaneous lung metastasis. In vitro and in vivo assays reveal that human
      and mouse platelet alpha6beta1 supports platelet adhesion to various types of
      cancer cells. Using a knockdown approach, we identified ADAM9 as the major
      counter receptor of alpha6beta1 on both human and mouse tumor cells. Static and
      flow-based adhesion assays of platelets binding to DC-9, a recombinant protein
      covering the disintegrin-cysteine domain of ADAM9, demonstrated that this
      receptor directly binds to platelet alpha6beta1. In vivo studies showed that the
      interplay between platelet alpha6beta1 and tumor cell-expressed ADAM9 promotes
      efficient lung metastasis. The integrin alpha6beta1-dependent platelet-tumor cell
      interaction induces platelet activation and favors the extravasation process of
      tumor cells. Finally, we demonstrate that a pharmacological approach targeting
      alpha6beta1 efficiently impairs tumor metastasis through a platelet-dependent
      mechanism. Our study reveals a mechanism by which platelets promote tumor
      metastasis and suggests that integrin alpha6beta1 represents a promising target
      for antimetastatic therapies.

PMID- 27699238
TI  - CFTR gene transfer with AAV improves early cystic fibrosis pig phenotypes.
AB  - The physiological components that contribute to cystic fibrosis (CF) lung disease
      are steadily being elucidated. Gene therapy could potentially correct these
      defects. CFTR-null pigs provide a relevant model to test gene therapy vectors.
      Using an in vivo selection strategy that amplifies successful capsids by
      replicating their genomes with helper adenovirus coinfection, we selected an
      adeno-associated virus (AAV) with tropism for pig airway epithelia. The evolved
      capsid, termed AAV2H22, is based on AAV2 with 5 point mutations that result in a
      240-fold increased infection efficiency. In contrast to AAV2, AAV2H22 binds
      specifically to pig airway epithelia and is less reliant on heparan sulfate for
      transduction. We administer AAV2H22-CFTR expressing the CF transmembrane
      conductance regulator (CFTR) cDNA to the airways of CF pigs. The transduced
      airways expressed CFTR on ciliated and nonciliated cells, induced anion
      transport, and improved the airway surface liquid pH and bacterial killing. Most
      gene therapy studies to date focus solely on Cl- transport as the primary metric
      of phenotypic correction. Here, we describe a gene therapy experiment where we
      not only correct defective anion transport, but also restore bacterial killing in
      CFTR-null pig airways.

PMID- 27699239
TI  - Multiparametric profiling of non-small-cell lung cancers reveals distinct
      immunophenotypes.
AB  - BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients
      with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict
      response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding
      of the diversity of the NSCLC tumor immune microenvironment remains limited.
      METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor
      and immune cells from 51 NSCLCs and integrated this analysis with clinical and
      histopathologic characteristics, next-generation sequencing, mRNA expression, and
      PD-L1 immunohistochemistry (IHC). RESULTS. Cytometric profiling identified an
      immunologically "hot" cluster with abundant CD8+ T cells expressing high levels
      of PD-1 and TIM-3 and an immunologically "cold" cluster with lower relative
      abundance of CD8+ T cells and expression of inhibitory markers. The "hot" cluster
      was highly enriched for expression of genes associated with T cell trafficking
      and cytotoxic function and high PD-L1 expression by IHC. There was no correlation
      between immunophenotype and KRAS or EGFR mutation, or patient smoking history,
      but we did observe an enrichment of squamous subtype and tumors with higher
      mutation burden in the "hot" cluster. Additionally, approximately 20% of cases
      had high B cell infiltrates with a subset producing IL-10. CONCLUSIONS. Our
      results support the use of immune-based metrics to study response and resistance
      to immunotherapy in lung cancer. FUNDING. The Robert A. and Renee E. Belfer
      Family Foundation, Expect Miracles Foundation, Starr Cancer Consortium, Stand Up
      to Cancer Foundation, Conquer Cancer Foundation, International Association for
      the Study of Lung Cancer, National Cancer Institute (R01 CA205150), and the Damon
      Runyon Cancer Research Foundation.

PMID- 27699240
TI  - Diphtheria toxin-mediated ablation of lymphatic endothelial cells results in
      progressive lymphedema.
AB  - Development of novel treatments for lymphedema has been limited by the fact that
      the pathophysiology of this disease is poorly understood. It remains unknown, for
      example, why limb swelling resulting from surgical injury resolves initially, but
      recurs in some cases months or years later. Finding answers for these basic
      questions has been hampered by the lack of adequate animal models. In the current
      study, we used Cre-lox mice that expressed the human diphtheria toxin receptor
      (DTR) driven by a lymphatic-specific promoter in order to noninvasively ablate
      the lymphatic system of the hind limb. Animals treated in this manner developed
      lymphedema that was indistinguishable from clinical lymphedema temporally,
      radiographically, and histologically. Using this model and clinical biopsy
      specimens, we show that the initial resolution of edema after injury is dependent
      on the formation of collateral capillary lymphatics and that this process is
      regulated by M2-polarized macrophages. In addition, we show that despite these
      initial improvements in lymphatic function, persistent accumulation of CD4+ cells
      inhibits lymphangiogenesis and promotes sclerosis of collecting lymphatics,
      resulting in late onset of edema and fibrosis. Our findings therefore provide
      strong evidence that inflammatory changes after lymphatic injury play a key role
      in the pathophysiology of lymphedema.

PMID- 27699242
TI  - Flow-metabolism dissociation in the pathogenesis of levodopa-induced dyskinesia.
AB  - Levodopa-induced dyskinesia (LID) is the most common, disruptive complication of
      Parkinson's disease (PD) pharmacotherapy, yet despite decades of research, the
      changes in regional brain function underlying LID remain largely unknown. We
      previously found that the cerebral vasomotor and metabolic responses to levodopa
      are dissociated in PD subjects. Nonetheless, it is unclear whether levodopa
      mediated dissociation is exaggerated in LID or distinguishes LID from non-LID
      subjects. To explore this possibility, we used dual-tracer positron emission
      tomography to quantify regional cerebral blood flow and metabolic activity in 28
      PD subjects (14 LID, 14 non-LID), scanned before and during intravenous levodopa
      infusion. Levodopa-mediated dissociation was most prominent in the posterior
      putamen (P < 0.0001) and greater in LID than in non-LID and test-retest subjects.
      Strikingly, LID subjects also showed increased sensorimotor cortex (SMC) activity
      in the baseline, unmedicated state. Imaging data from an independent PD sample
      (106 subjects) linked these differences to loss of mesocortical dopamine
      terminals in advanced patients. In aggregate, the data suggest that LID results
      from an overactive vasomotor response to levodopa in the putamen on a background
      of disease-related increases in SMC activity. LID may thus be amenable to
      treatment that modulates the function of these 2 regions.

PMID- 27699241
TI  - Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against
      Toxoplasma gondii.
AB  - We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand
      emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion [GLA
      SE]) for their ability to protect against Toxoplasma gondii in HLA transgenic
      mice. Our constructs each included 5 of our best down-selected CD8+ T cell
      eliciting epitopes, a universal CD4+ helper T lymphocyte epitope (PADRE), and a
      secretory signal, all arranged for optimal MHC-I presentation. Their capacity to
      elicit immune and protective responses was studied using immunization of HLA
      A*11:01 transgenic mice. These multi-epitope vaccines increased memory CD8+ T
      cells that produced IFN-gamma and protected mice against parasite burden when
      challenged with T. gondii. Endocytosis of emulsion-trapped protein and cross
      presentation of the antigens must account for the immunogenicity of our
      adjuvanted protein. Thus, our work creates an adjuvanted platform assembly of
      peptides resulting in cross presentation of CD8+ T cell-eliciting epitopes in a
      vaccine that prevents toxoplasmosis.

PMID- 27699243
TI  - Autophagy-dependent regulatory T cells are critical for the control of graft
      versus-host disease.
AB  - Regulatory T cells (Tregs) play a crucial role in the maintenance of peripheral
      tolerance. Quantitative and/or qualitative defects in Tregs result in diseases
      such as autoimmunity, allergy, malignancy, and graft-versus-host disease (GVHD),
      a serious complication of allogeneic stem cell transplantation (SCT). We recently
      reported increased expression of autophagy-related genes (Atg) in association
      with enhanced survival of Tregs after SCT. Autophagy is a self-degradative
      process for cytosolic components that promotes cell homeostasis and survival.
      Here, we demonstrate that the disruption of autophagy within FoxP3+ Tregs
      (B6.Atg7fl/fl-FoxP3cre+ ) resulted in a profound loss of Tregs, particularly
      within the bone marrow (BM). This resulted in dysregulated effector T cell
      activation and expansion, and the development of enterocolitis and scleroderma in
      aged mice. We show that the BM compartment is highly enriched in TIGIT+ Tregs and
      that this subset is differentially depleted in the absence of autophagy.
      Moreover, following allogeneic SCT, recipients of grafts from B6.Atg7fl/fl
      FoxP3cre+ donors exhibited reduced Treg reconstitution, exacerbated GVHD, and
      reduced survival compared with recipients of B6.WT-FoxP3cre+ grafts.
      Collectively, these data indicate that autophagy-dependent Tregs are critical for
      the maintenance of tolerance after SCT and that the promotion of autophagy
      represents an attractive immune-restorative therapeutic strategy after allogeneic
      SCT.

PMID- 27699245
TI  - A ferret model of COPD-related chronic bronchitis.
AB  - Chronic obstructive pulmonary disease (COPD) is the third leading cause of death
      in the US. The majority of COPD patients have symptoms of chronic bronchitis,
      which lacks specific therapies. A major impediment to therapeutic development has
      been the absence of animal models that recapitulate key clinical and pathologic
      features of human disease. Ferrets are well suited for the investigation of the
      significance of respiratory diseases, given prior data indicating similarities to
      human airway physiology and submucosal gland distribution. Here, we exposed
      ferrets to chronic cigarette smoke and found them to approximate complex clinical
      features of human COPD. Unlike mice, which develop solely emphysema, smoke
      exposed ferrets exhibited markedly higher numbers of early-morning spontaneous
      coughs and sporadic infectious exacerbations as well as a higher level of airway
      obstruction accompanied by goblet cell metaplasia/hyperplasia and increased mucus
      expression in small airways, indicative of chronic bronchitis and bronchiolitis.
      Overall, we demonstrate the first COPD animal model exhibiting clinical and
      pathologic features of chronic bronchitis to our knowledge, providing a key
      advance that will greatly facilitate the preclinical development of novel
      treatments for this disease.

PMID- 27699244
TI  - Tissue-specific metabolic reprogramming drives nutrient flux in diabetic
      complications.
AB  - Diabetes is associated with altered cellular metabolism, but how altered
      metabolism contributes to the development of diabetic complications is unknown.
      We used the BKS db/db diabetic mouse model to investigate changes in carbohydrate
      and lipid metabolism in kidney cortex, peripheral nerve, and retina. A systems
      approach using transcriptomics, metabolomics, and metabolic flux analysis
      identified tissue-specific differences, with increased glucose and fatty acid
      metabolism in the kidney, a moderate increase in the retina, and a decrease in
      the nerve. In the kidney, increased metabolism was associated with enhanced
      protein acetylation and mitochondrial dysfunction. To confirm these findings in
      human disease, we analyzed diabetic kidney transcriptomic data and urinary
      metabolites from a cohort of Southwestern American Indians. The urinary findings
      were replicated in 2 independent patient cohorts, the Finnish Diabetic
      Nephropathy and the Family Investigation of Nephropathy and Diabetes studies.
      Increased concentrations of TCA cycle metabolites in urine, but not in plasma,
      predicted progression of diabetic kidney disease, and there was an enrichment of
      pathways involved in glycolysis and fatty acid and amino acid metabolism. Our
      findings highlight tissue-specific changes in metabolism in complication-prone
      tissues in diabetes and suggest that urinary TCA cycle intermediates are
      potential prognostic biomarkers of diabetic kidney disease progression.

PMID- 27699246
TI  - MUTYH promotes oxidative microglial activation and inherited retinal
      degeneration.
AB  - Oxidative stress is implicated in various neurodegenerative disorders, including
      retinitis pigmentosa (RP), an inherited disease that causes blindness. The
      biological and cellular mechanisms by which oxidative stress mediates neuronal
      cell death are largely unknown. In a mouse model of RP (rd10 mice), we show that
      oxidative DNA damage activates microglia through MutY homolog-mediated (MUYTH
      mediated) base excision repair (BER), thereby exacerbating retinal inflammation
      and degeneration. In the early stage of retinal degeneration, oxidative DNA
      damage accumulated in the microglia and caused single-strand breaks (SSBs) and
      poly(ADP-ribose) polymerase activation. In contrast, Mutyh deficiency in rd10
      mice prevented SSB formation in microglia, which in turn suppressed microglial
      activation and photoreceptor cell death. Moreover, Mutyh-deficient primary
      microglial cells attenuated the polarization to the inflammatory and cytotoxic
      phenotype under oxidative stress. Thus, MUTYH-mediated BER in oxidative
      microglial activation may be a novel target to dampen the disease progression in
      RP and other neurodegenerative disorders that are associated with oxidative
      stress.

PMID- 27699247
TI  - PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in
      primary pigmented nodular adrenal disease.
AB  - Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH
      independent hypercortisolism. The disease is primarily caused by germline
      mutations of the protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene,
      which induces constitutive activation of PKA in adrenocortical cells.
      Hypercortisolism is thought to result from PKA hyperactivity, but PPNAD tissues
      exhibit features of neuroendocrine differentiation, which may lead to stimulation
      of steroidogenesis by abnormally expressed neurotransmitters. We hypothesized
      that serotonin (5-HT) may participate in the pathophysiology of PPNAD-associated
      hypercortisolism. We show that PPNAD tissues overexpress the 5-HT synthesizing
      enzyme tryptophan hydroxylase type 2 (Tph2) and the serotonin receptors types 4,
      6, and 7, leading to formation of an illicit stimulatory serotonergic loop whose
      pharmacological inhibition in vitro decreases cortisol production. In the human
      PPNAD cell line CAR47, the PKA inhibitor H-89 decreases 5-HT4 and 5-HT7 receptor
      expression. Moreover, in the human adrenocortical cell line H295R, inhibition of
      PRKAR1A expression increases the expression of Tph2 and 5-HT4/6/7 receptors, an
      effect that is blocked by H-89. These findings show that the serotonergic process
      observed in PPNAD tissues results from PKA activation by PRKAR1A mutations. They
      also suggest that Tph inhibitors may represent efficient treatments of
      hypercortisolism in patients with PPNAD.

PMID- 27699248
TI  - Bladder catheterization increases susceptibility to infection that can be
      prevented by prophylactic antibiotic treatment.
AB  - Catheter-associated urinary tract infections (CAUTI) are the most common hospital
      associated infections. Here, we report that bladder catheterization initiated a
      persistent sterile inflammatory reaction within minutes of catheter implantation.
      Catheterization resulted in increased expression of genes associated with defense
      responses and cellular migration, with ensuing rapid and sustained innate immune
      cell infiltration into the bladder. Catheterization also resulted in
      hypersensitivity to Enterococcus faecalis and uropathogenic Escherichia coli
      (UPEC) infection, in which colonization was achieved using an inoculum 100-fold
      lower than the ID90 for infection of an undamaged urothelium with the same
      uropathogens. As the time of catheterization increased, however, colonization by
      the Gram-positive uropathogen E. faecalis was reduced, whereas catheterization
      created a sustained window of vulnerability to infection for Gram-negative UPEC
      over time. As CAUTI contributes to poorer patient outcomes and increased health
      care expenditures, we tested whether a single prophylactic antibiotic treatment,
      concurrent with catheterization, would prevent infection. We observed that
      antibiotic treatment protected against UPEC and E. faecalis bladder and catheter
      colonization as late as 6 hours after implantation. Thus, our study has revealed
      a simple, safe, and immediately employable intervention, with the potential to
      decrease one of the most costly hospital-incurred infections, thereby improving
      patient and health care economic outcome.

PMID- 27699249
TI  - A xenograft model of macrophage activation syndrome amenable to anti-CD33 and
      anti-IL-6R treatment.
AB  - Transgenic expression of key myelosupportive human cytokines in immune-deficient
      mice corrects for the lack of cross-species activities of stem cell factor (SCF),
      IL-3, and GM-CSF. When engrafted with human umbilical cord blood (UCB), these
      triple-transgenic mice produce BM and spleen grafts with much higher myeloid
      composition, relative to nontransgenic controls. Shortly after engraftment with
      UCB, these mice develop a severe, fatal macrophage activation syndrome (MAS)
      characterized by a progressive drop in rbc numbers, increased reticulocyte
      counts, decreased rbc half-life, progressive cytopenias, and evidence of chronic
      inflammation, including elevated human IL-6. The BM becomes strikingly
      hypocellular, and spleens are significantly enlarged with evidence of
      extramedullary hematopoiesis and activated macrophages engaged in
      hemophagocytosis. This manifestation of MAS does not respond to lymphocyte
      suppressive therapies such as steroids, i.v. immunoglobulin, or antibody-mediated
      ablation of human B and T cells, demonstrating a lymphocyte-independent mechanism
      of action. In contrast, elimination of human myeloid cells using gemtuzumab
      ozogamicin (anti-CD33) completely reversed the disease. Additionally, the IL-6R
      antibody tocilizumab delayed progression and prolonged lifespan. This new model
      of MAS provides an opportunity for investigation of the mechanisms driving this
      disease and for the testing of directed therapies in a humanized mouse.

PMID- 27699250
TI  - One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of
      insulin resistance.
AB  - Using mice rendered insulin resistant with high fat diets (HFD), we examined
      blood glucose levels and insulin resistance after i.v. delivery of an adeno
      associated virus type 8 encoding murine urocortin 2 (AAV8.UCn2). A single i.v.
      injection of AAV8.UCn2-normalized blood glucose and glucose disposal within
      weeks, an effect that lasted for months. Hyperinsulinemic-euglycemic clamps
      showed reduced plasma insulin, increased glucose disposal rates, and increased
      insulin sensitivity following UCn2 gene transfer. Mice with corticotropin
      releasing hormone type 2-receptor deletion that were rendered insulin resistant
      by HFD showed no improvement in glucose disposal after UCn2 gene transfer,
      indicating that the effect requires UCn2's cognate receptor. We also demonstrated
      increased glucose disposal after UCn2 gene transfer in db/db mice, a second model
      of insulin resistance. UCn2 gene transfer reduced fatty infiltration of the liver
      in both models of insulin resistance. UCn2 increases Glut4 translocation to the
      plasma membrane in skeletal myotubes in a manner quantitatively similar to
      insulin, indicating a mechanism through which UCn2 operates to increase insulin
      sensitivity. UCn2 gene transfer, in a dose-dependent manner, is insulin
      sensitizing and effective for months after a single injection. These findings
      suggest a potential long-term therapy for clinical type-2 diabetes.

PMID- 27699252
TI  - Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with
      alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by hair
      loss mediated by CD8+ T cells. There are no reliably effective therapies for AA.
      Based on recent developments in the understanding of the pathomechanism of AA,
      JAK inhibitors appear to be a therapeutic option; however, their efficacy for the
      treatment of AA has not been systematically examined. METHODS: This was a 2
      center, open-label, single-arm trial using the pan-JAK inhibitor, tofacitinib
      citrate, for AA with >50% scalp hair loss, alopecia totalis (AT), and alopecia
      universalis (AU). Tofacitinib (5 mg) was given twice daily for 3 months.
      Endpoints included regrowth of scalp hair, as assessed by the severity of
      alopecia tool (SALT), duration of hair growth after completion of therapy, and
      disease transcriptome. RESULTS: Of 66 subjects treated, 32% experienced 50% or
      greater improvement in SALT score. AA and ophiasis subtypes were more responsive
      than AT and AU subtypes. Shorter duration of disease and histological peribulbar
      inflammation on pretreatment scalp biopsies were associated with improvement in
      SALT score. Drug cessation resulted in disease relapse in 8.5 weeks. Adverse
      events were limited to grade I and II infections. An AA responsiveness to
      JAK/STAT inhibitors score was developed to segregate responders and
      nonresponders, and the previously developed AA disease activity index score
      tracked response to treatment. CONCLUSIONS: At the dose and duration studied,
      tofacitinib is a safe and effective treatment for severe AA, though it does not
      result in a durable response. Transcriptome changes reveal unexpected molecular
      complexity within the disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT02197455
      and NCT02312882. FUNDING: This work was supported by the US Department of
      Veterans Affairs Office of Research and Development, National Institute of
      Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health
      grant R01 AR47223 and U01 AR67173, the National Psoriasis Foundation, the Swedish
      Society of Medicine, the Fernstrom Foundation, the Locks of Love Foundation, the
      National Alopecia Areata Foundation, and the Ranjini and Ajay Poddar Resource
      Fund for Dermatologic Diseases Research.

PMID- 27699253
TI  - Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe
      alopecia areata.
AB  - BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime
      risk of 1.7%; there are no FDA-approved treatments for AA. We previously
      identified a dominant IFN-gamma transcriptional signature in cytotoxic T
      lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK
      inhibitors induced durable hair regrowth in mice by targeting this pathway. Here,
      we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment
      of patients with moderate-to-severe AA. METHODS. We initiated an open-label
      clinical trial of 12 patients with moderate-to-severe AA, using oral ruxolitinib,
      20 mg twice per day, for 3-6 months of treatment followed by 3 months follow-up
      off drug. The primary endpoint was the proportion of subjects with 50% or greater
      hair regrowth from baseline to end of treatment. RESULTS. Nine of twelve patients
      (75%) demonstrated a remarkable response to treatment, with average hair regrowth
      of 92% at the end of treatment. Safety parameters remained largely within normal
      limits, and no serious adverse effects were reported. Gene expression profiling
      revealed treatment-related downregulation of inflammatory markers, including
      signatures for CTLs and IFN response genes and upregulation of hair-specific
      markers. CONCLUSION. In this pilot study, 9 of 12 patients (75%) treated with
      ruxolitinib showed significant scalp hair regrowth and improvement of AA. Larger
      randomized controlled trials are needed to further assess the safety and efficacy
      of ruxolitinib in the treatment of AA. TRIAL REGISTRATION. Clinicaltrials.gov
      NCT01950780. FUNDING. Locks of Love Foundation, the Alopecia Areata Initiative,
      NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
      (NIAMS), and the Irving Institute for Clinical and Translational
      Research/Columbia University Medical Center Clinical and Translational Science
      Award (CUMC CTSA).

PMID- 27699251
TI  - Cell-type deconvolution with immune pathways identifies gene networks of host
      defense and immunopathology in leprosy.
AB  - Transcriptome profiles derived from the site of human disease have led to the
      identification of genes that contribute to pathogenesis, yet the complex mixture
      of cell types in these lesions has been an obstacle for defining specific
      mechanisms. Leprosy provides an outstanding model to study host defense and
      pathogenesis in a human infectious disease, given its clinical spectrum, which
      interrelates with the host immunologic and pathologic responses. Here, we
      investigated gene expression profiles derived from skin lesions for each clinical
      subtype of leprosy, analyzing gene coexpression modules by cell-type
      deconvolution. In lesions from tuberculoid leprosy patients, those with the self
      limited form of the disease, dendritic cells were linked with MMP12 as part of a
      tissue remodeling network that contributes to granuloma formation. In lesions
      from lepromatous leprosy patients, those with disseminated disease, macrophages
      were linked with a gene network that programs phagocytosis. In erythema nodosum
      leprosum, neutrophil and endothelial cell gene networks were identified as part
      of the vasculitis that results in tissue injury. The present integrated
      computational approach provides a systems approach toward identifying cell
      defined functional networks that contribute to host defense and immunopathology
      at the site of human infectious disease.

PMID- 27699254
TI  - Dynamic dual-isotope molecular imaging elucidates principles for optimizing
      intrathecal drug delivery.
AB  - The intrathecal (IT) dosing route offers a seemingly obvious solution for
      delivering drugs directly to the central nervous system. However, gaps in
      understanding drug molecule behavior within the anatomically and kinetically
      unique environment of the mammalian IT space have impeded the establishment of
      pharmacokinetic principles for optimizing regional drug exposure along the
      neuraxis. Here, we have utilized high-resolution single-photon emission
      tomography with X-ray computed tomography to study the behavior of multiple
      molecular imaging tracers following an IT bolus injection, with supporting
      histology, autoradiography, block-face tomography, and MRI. Using simultaneous
      dual-isotope imaging, we demonstrate that the regional CNS tissue exposure of
      molecules with varying chemical properties is affected by IT space anatomy,
      cerebrospinal fluid (CSF) dynamics, CSF clearance routes, and the location and
      volume of the injected bolus. These imaging approaches can be used across species
      to optimize the safety and efficacy of IT drug therapy for neurological
      disorders.

PMID- 27699255
TI  - Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical,
      genomic, and functional analysis.
AB  - The 2p15p16.1 microdeletion syndrome has a core phenotype consisting of
      intellectual disability, microcephaly, hypotonia, delayed growth, common
      craniofacial features, and digital anomalies. So far, more than 20 cases of
      2p15p16.1 microdeletion syndrome have been reported in the literature; however,
      the size of the deletions and their breakpoints vary, making it difficult to
      identify the candidate genes. Recent reports pointed to 4 genes (XPO1, USP34,
      BCL11A, and REL) that were included, alone or in combination, in the smallest
      deletions causing the syndrome. Here, we describe 8 new patients with the
      2p15p16.1 deletion and review all published cases to date. We demonstrate
      functional deficits for the above 4 candidate genes using patients' lymphoblast
      cell lines (LCLs) and knockdown of their orthologs in zebrafish. All genes were
      dosage sensitive on the basis of reduced protein expression in LCLs. In addition,
      deletion of XPO1, a nuclear exporter, cosegregated with nuclear accumulation of
      one of its cargo molecules (rpS5) in patients' LCLs. Other pathways associated
      with these genes (e.g., NF-kappaB and Wnt signaling as well as the DNA damage
      response) were not impaired in patients' LCLs. Knockdown of xpo1a, rel, bcl11aa,
      and bcl11ab resulted in abnormal zebrafish embryonic development including
      microcephaly, dysmorphic body, hindered growth, and small fins as well as
      structural brain abnormalities. Our multifaceted analysis strongly implicates
      XPO1, REL, and BCL11A as candidate genes for 2p15p16.1 microdeletion syndrome.

PMID- 27699257
TI  - Interleukin-1 signaling contributes to acute islet compensation.
AB  - IL-1beta is a well-established inducer of both insulin resistance and impaired
      pancreatic islet function. Despite this, findings examining IL-1 receptor
      deficiency or antagonism in in vivo animal models, as well as in clinical studies
      of type 2 diabetic (T2D) patients, have led to conflicting results, suggesting
      that the actions of IL-1beta on glycemic control may be pleiotropic in nature. In
      the present work, we find that the ability of IL-1beta to amplify glucose
      stimulated insulin secretion from human islets correlates with donor BMI. Islets
      from obese donors are sensitized to the insulinotropic effects of this cytokine,
      whereas the stimulatory effects of IL-1beta are lost in islets from obese T2D
      patients, suggesting a role for IL-1 signaling in islet compensation. Indeed,
      mice deficient in IL-1 receptor type I become glucose intolerant more rapidly
      than their WT littermates and have impaired secretory responses during the acute
      stages of inflammatory and metabolic stress induced by LPS and high-fat diet,
      respectively. IL-1beta directly enhances beta cell insulin secretion by
      increasing granule docking and soluble N-ethylmaleimide-sensitive factor
      attachment receptor (SNARE) complex formation at the plasma membrane. Together,
      our study highlights the importance of IL-1beta signaling in islet compensation
      to metabolic and inflammatory stress.

PMID- 27699256
TI  - Claudin-low bladder tumors are immune infiltrated and actively immune suppressed.
AB  - We report the discovery of a claudin-low molecular subtype of high-grade bladder
      cancer that shares characteristics with the homonymous subtype of breast cancer.
      Claudin-low bladder tumors were enriched for multiple genetic features including
      increased rates of RB1, EP300, and NCOR1 mutations; increased frequency of EGFR
      amplification; decreased rates of FGFR3, ELF3, and KDM6A mutations; and decreased
      frequency of PPARG amplification. While claudin-low tumors showed the highest
      expression of immune gene signatures, they also demonstrated gene expression
      patterns consistent with those observed in active immunosuppression. This did not
      appear to be due to differences in predicted neoantigen burden, but rather was
      associated with broad upregulation of cytokine and chemokine levels from low
      PPARG activity, allowing unopposed NFKB activity. Taken together, these results
      define a molecular subtype of bladder cancer with distinct molecular features and
      an immunologic profile that would, in theory, be primed for immunotherapeutic
      response.

PMID- 27699258
TI  - Histone deacetylase inhibitor panobinostat induces calcineurin degradation in
      multiple myeloma.
AB  - Multiple myeloma (MM) is a relapsed and refractory disease, one that highlights
      the need for developing new molecular therapies for overcoming of drug
      resistance. Addition of panobinostat, a histone deacetylase (HDAC) inhibitor, to
      bortezomib and dexamethasone improved progression-free survival (PFS) in relapsed
      and refractory MM patients. Here, we demonstrate how calcineurin, when inhibited
      by immunosuppressive drugs like FK506, is involved in myeloma cell growth and
      targeted by panobinostat. mRNA expression of PPP3CA, a catalytic subunit of
      calcineurin, was high in advanced patients. Panobinostat degraded PPP3CA, a
      degradation that should have been induced by inhibition of the chaperone function
      of heat shock protein 90 (HSP90). Cotreatment with HDAC inhibitors and FK506 led
      to an enhanced antimyeloma effect with a greater PPP3CA reduction compared with
      HDAC inhibitors alone both in vitro and in vivo. In addition, this combination
      treatment efficiently blocked osteoclast formation, which results in osteolytic
      lesions. The poor response and short PFS duration observed in the bortezomib
      containing therapies of patients with high PPP3CA suggested its relevance to
      bortezomib resistance. Moreover, bortezomib and HDAC inhibitors synergistically
      suppressed MM cell viability through PPP3CA inhibition. Our findings underscore
      the usefulness of calcineurin-targeted therapy in MM patients, including patients
      who are resistant to bortezomib.

PMID- 27699259
TI  - Microvascular resistance of the culprit coronary artery in acute ST-elevation
      myocardial infarction.
AB  - BACKGROUND: Failed myocardial reperfusion is common and prognostically important
      after acute ST-elevation myocardial infarction (STEMI). The purpose of this study
      was to investigate coronary flow reserve (CFR), a measure of vasodilator
      capacity, and the index of microvascular resistance (IMR; mmHg * s) in the
      culprit artery of STEMI survivors. METHODS: IMR (n = 288) and CFR (n = 283; mean
      age [SD], 60 [12] years) were measured acutely using guide wire-based
      thermodilution. Cardiac MRI disclosed left ventricular pathology, function, and
      volumes at 2 days (n = 281) and 6 months after STEMI (n = 264). All-cause death
      or first heart failure hospitalization was independently adjudicated (median
      follow-up 845 days). RESULTS: Myocardial hemorrhage and microvascular obstruction
      occurred in 89 (42%) and 114 (54%) patients with evaluable T2*-MRI maps. IMR and
      CFR were associated with microvascular pathology (none vs. microvascular
      obstruction only vs. microvascular obstruction and myocardial hemorrhage) (median
      [interquartile range], IMR: 17 [12.0-33.0] vs. 17 [13.0-39.0] vs. 37 [21.0-63.0],
      P < 0.001; CFR: 1.7 [1.4-2.5] vs. 1.5 [1.1-1.8] vs. 1.4 [1.0-1.8], P < 0.001),
      whereas thrombolysis in myocardial infarction blush grade was not. IMR was a
      multivariable associate of changes in left ventricular end-diastolic volume
      (regression coefficient [95% CI] 0.13 [0.01, 0.24]; P = 0.036), whereas CFR was
      not (P = 0.160). IMR (5 units) was a multivariable associate of all-cause death
      or heart failure hospitalization (n = 30 events; hazard ratio [95% CI], 1.09
      [1.04, 1.14]; P < 0.001), whereas CFR (P = 0.124) and thrombolysis in myocardial
      infarction blush grade (P = 0.613) were not. IMR had similar prognostic value for
      these outcomes as <50% ST-segment resolution on the ECG. CONCLUSIONS: IMR is more
      closely associated with microvascular pathology, left ventricular remodeling, and
      health outcomes than the angiogram or CFR. TRIAL REGISTRATION: NCT02072850.
      FUNDING: A British Heart Foundation Project Grant (PG/11/2/28474), the National
      Health Service, the Chief Scientist Office, a Scottish Funding Council Senior
      Fellowship, a British Heart Foundation Intermediate Fellowship (FS/12/62/29889),
      and a nonfinancial research agreement with Siemens Healthcare.

PMID- 27699261
TI  - Anakinra as a diagnostic challenge and treatment option for systemic
      autoinflammatory disorders of undefined etiology.
AB  - BACKGROUND: Some adult patients presenting with unexplained pyrexia, serositis,
      skin rashes, arthralgia, myalgia, and other symptoms commonly found in
      autoinflammatory disorders may not fit a specific diagnosis, either because their
      clinical phenotype is nondiagnostic or genetic tests are negative. We used the
      term undifferentiated systemic autoinflammatory disorder (uSAID) to describe such
      cases. Given that well-defined autoinflammatory diseases show responses to IL-1
      blockade, we evaluated whether anakinra was useful for both diagnosing and
      treating uSAID patients. METHODS: We performed a retrospective analysis of
      consecutive patients presenting with uSAID between 2012-2015 who were treated
      with the recombinant IL-1 receptor antagonist anakinra. uSAID was diagnosed after
      excluding malignancy, infection, and pathogenic mutations in known hereditary
      fever syndromes (HFS) genes and where clinical criteria for adult onset Still's
      disease (AOSD) were not met. RESULTS: A total of 11 patients presented with uSAID
      (5 males and 6 females), with a mean time to diagnosis of 3.5 years (1-8 years).
      Patients were unresponsive or only partially controlled on disease-modifying
      antirheumatic drug (DMARD)/steroid treatment. Anakinra controlled symptoms within
      4-6 weeks of starting treatment in 9 of 11 cases. Two patients discontinued
      therapy - one due to incomplete response and another due to severe injection-site
      reactions. CONCLUSION: This retrospective case series demonstrates that the
      spectrum of poorly defined autoinflammatory disorders that show responsiveness to
      anakinra is considerable. Anakinra seems a viable treatment option for these
      patients, who are unresponsive to standard steroid/DMARD treatments. Moreover,
      given the mechanisms of action, response to anakinra implicates underlying IL-1
      dysregulation in the disease pathogenesis of responding uSAIDs patients.

PMID- 27699260
TI  - A cytotoxic anti-IL-3Ralpha antibody targets key cells and cytokines implicated
      in systemic lupus erythematosus.
AB  - To date, the major target of biologic therapeutics in systemic lupus
      erythematosus (SLE) has been the B cell, which produces pathogenic
      autoantibodies. Recently, targeting type I IFN, which is elaborated by
      plasmacytoid dendritic cells (pDCs) in response to endosomal TLR7 and TLR9
      stimulation by SLE immune complexes, has shown promising results. pDCs express
      high levels of the IL-3Ralpha chain (CD123), suggesting an alternative potential
      targeting strategy. We have developed an anti-CD123 monoclonal antibody, CSL362,
      and show here that it affects key cell types and cytokines that contribute to
      SLE. CSL362 potently depletes pDCs via antibody-dependent cell-mediated
      cytotoxicity, markedly reducing TLR7, TLR9, and SLE serum-induced IFN-alpha
      production and IFN-alpha-upregulated gene expression. The antibody also inhibits
      TLR7- and TLR9-induced plasmablast expansion by reducing IFN-alpha and IL-6
      production. These effects are more pronounced than with IFN-alpha blockade alone,
      possibly because pDC depletion reduces production of other IFN subtypes, such as
      type III, as well as non-IFN proinflammatory cytokines, such as IL-6. In
      addition, CSL362 depletes basophils and inhibits IL-3 signaling. These effects
      were confirmed in cells derived from a heterogeneous population of SLE donors,
      various IFN-dependent autoimmune diseases, and healthy controls. We also
      demonstrate in vivo activity of CSL362 following its s.c. administration to
      cynomolgus monkeys. This spectrum of effects provides a preclinical rationale for
      the therapeutic evaluation of CSL362 in SLE.

PMID- 27699262
TI  - Increased apoptosis and browning of TAK1-deficient adipocytes protects against
      obesity.
AB  - Obesity is an increasing health problem worldwide, and nonsurgical strategies to
      treat obesity have remained rather inefficient. We here show that acute loss of
      TGF-beta-activated kinase 1 (TAK1) in adipocytes results in an increased rate of
      apoptotic adipocyte death and increased numbers of M2 macrophages in white
      adipose tissue. Mice with adipocyte-specific TAK1 deficiency have reduced
      adipocyte numbers and are resistant to obesity induced by a high-fat diet or
      leptin deficiency. In addition, adipocyte-specific TAK1-deficient mice under a
      high-fat diet showed increased energy expenditure, which was accompanied by
      enhanced expression of the uncoupling protein UCP1. Interestingly, acute
      induction of adipocyte-specific TAK1 deficiency in mice already under a high-fat
      diet was able to stop further weight gain and improved glucose tolerance. Thus,
      loss of TAK1 in adipocytes reduces the total number of adipocytes, increases
      browning of white adipose tissue, and may be an attractive strategy to treat
      obesity, obesity-dependent diabetes, and other associated complications.

PMID- 27699263
TI  - Incomplete clonal deletion as prerequisite for tissue-specific minor antigen
      tolerization.
AB  - Central clonal deletion has been considered the critical factor responsible for
      the robust state of tolerance achieved by chimerism-based experimental protocols,
      but split-tolerance models and the clinical experience are calling this
      assumption into question. Although clone-size reduction through deletion has been
      shown to be universally required for achieving allotolerance, it remains
      undetermined whether it is sufficient by itself. Therapeutic Treg treatment
      induces chimerism and tolerance in a stringent murine BM transplantation model
      devoid of myelosuppressive recipient treatment. In contrast to irradiation
      chimeras, chronic rejection (CR) of skin and heart allografts in Treg chimeras
      was permanently prevented, even in the absence of complete clonal deletion of
      donor MHC-reactive T cells. We show that minor histocompatibility antigen
      mismatches account for CR in irradiation chimeras without global T cell
      depletion. Furthermore, we show that Treg therapy-induced tolerance prevents CR
      in a linked suppression-like fashion, which is maintained by active regulatory
      mechanisms involving recruitment of thymus-derived Tregs to the graft. These data
      suggest that highly efficient intrathymic and peripheral deletion of donor
      reactive T cells for specificities expressed on hematopoietic cells preclude the
      expansion of donor-specific Tregs and, hence, do not allow for spreading of
      tolerance to minor specificities that are not expressed by donor BM.

PMID- 27699265
TI  - Targeting CLEC9A delivers antigen to human CD141+ DC for CD4+ and CD8+T cell
      recognition.
AB  - DC-based vaccines that initiate T cell responses are well tolerated and have
      demonstrated efficacy for tumor immunotherapy, with the potential to be combined
      with other therapies. Targeting vaccine antigens (Ag) directly to the DCs in vivo
      is more effective than cell-based therapies in mouse models and is therefore a
      promising strategy to translate to humans. The human CD141+ DCs are considered
      the most clinically relevant for initiating CD8+ T cell responses critical for
      killing tumors or infected cells, and they specifically express the C-type lectin
      like receptor CLEC9A that facilitates presentation of Ag by these DCs. We have
      therefore developed a human chimeric Ab that specifically targets CLEC9A on
      CD141+ DCs in vitro and in vivo. These human chimeric Abs are highly effective at
      delivering Ag to DCs for recognition by both CD4+ and CD8+ T cells. Given the
      importance of these cellular responses for antitumor or antiviral immunity, and
      the superior specificity of anti-CLEC9A Abs for this DC subset, this approach
      warrants further development for vaccines.

PMID- 27699264
TI  - Depletion of major pathogenic cells in asthma by targeting CRTh2.
AB  - Eosinophilic inflammation and Th2 cytokine production are central to the
      pathogenesis of asthma. Agents that target either eosinophils or single Th2
      cytokines have shown benefits in subsets of biomarker-positive patients. More
      broadly effective treatment or disease-modifying effects may be achieved by
      eliminating more than one inflammatory stimulator. Here we present a strategy to
      concomitantly deplete Th2 T cells, eosinophils, basophils, and type-2 innate
      lymphoid cells (ILC2s) by generating monoclonal antibodies with enhanced effector
      function (19A2) that target CRTh2 present on all 4 cell types. Using human CRTh2
      (hCRTh2) transgenic mice that mimic the expression pattern of hCRTh2 on innate
      immune cells but not Th2 cells, we demonstrate that anti-hCRTh2 antibodies
      specifically eliminate hCRTh2+ basophils, eosinophils, and ILC2s from lung and
      lymphoid organs in models of asthma and Nippostrongylus brasiliensis infection.
      Innate cell depletion was accompanied by a decrease of several Th2 cytokines and
      chemokines. hCRTh2-specific antibodies were also active on human Th2 cells in
      vivo in a human Th2-PBMC-SCID mouse model. We developed humanized hCRTh2-specific
      antibodies that potently induce antibody-dependent cell cytotoxicity (ADCC) of
      primary human eosinophils and basophils and replicated the in vivo depletion
      capacity of their murine parent. Therefore, depletion of hCRTh2+ basophils,
      eosinophils, ILC2, and Th2 cells with h19A2 hCRTh2-specific antibodies may be a
      novel and more efficacious treatment for asthma.

PMID- 27699266
TI  - Cyclosporine A immunosuppression drives catastrophic squamous cell carcinoma
      through IL-22.
AB  - Immune-suppressed organ transplant recipients (OTRs) can develop catastrophic
      squamous cell carcinoma (SCC), characterized by multiple primary tumors,
      extensive body surface area involvement, or metastases. There are currently no
      curative systemic therapies available. We previously showed that IL-22 enhances
      SCC proliferation. Herein, we examined links between cyclosporine (CSA), IL-22,
      and SCC in patients, cell lines, and mice with UV light-induced SCC. Eighteen of
      114 OTRs developed catastrophic SCC, which was strongly associated with CSA
      treatment. We found that CSA drives T cell polarization toward IL-22-producing
      T22 cells, and CSA treatment increased IL-22 receptor in SCC cells. SCC tissue
      from OTRs showed increased expression of IL-22RA1. CSA potentiated rescue by IL
      22 of serum-starved SCC cells; treatment of SCC cells with IL-22 and CSA
      increased both their migratory and invasive capacity. In a UV-induced model of
      SCC in SKH-1 immunocompetent mice, treatment with anti-IL-22 antibody reduced
      tumor number and tumor burden. We found that catastrophic SCC in OTRs is
      associated with CSA use, which may be acting by favoring T22 polarization. Since
      anti-IL-22 antibody administration decreased tumor number and tumor burden in
      vivo, blockade of the IL-22 axis may be developed as a viable therapeutic option
      for catastrophic SCC.

PMID- 27699267
TI  - Quantitation of circulating satellite RNAs in pancreatic cancer patients.
AB  - Pancreatic ductal adenocarcinoma (Pdac) is a malignancy with a poor prognosis due
      to difficulties in early detection. Although promising biomarkers are
      increasingly reported, such methods are not yet easy to apply clinically, mainly
      due to their low reproducibility or technical difficulties. In this study, we
      developed a convenient and sensitive method for quantifying aberrantly expressed
      satellite repeat RNAs in sera, which can be used to efficiently detect patients
      with Pdac. Here, we introduce a Tandem Repeat Amplification by nuclease
      Protection (TRAP) method combined with droplet digital PCR (ddPCR) to detect
      human satellite II (HSATII) RNAs, which are specifically expressed in human Pdacs
      at greater levels than normal tissues but are difficult to measure due to their
      repetitive sequences and irregularities. HSATII RNA core sequence levels in sera
      were significantly higher in Pdac patients compared with noncancer patients
      (median copy number: 14.75 and 3.17 per MUl in the training set and 17.35 and 2.9
      in the validation set, respectively). In addition, patients with intraductal
      papillary mucinous neoplasm (IPMN), a precancerous lesion of Pdac, could also be
      efficiently detected. This method can be routinely applied to screen patients
      with Pdac and high-risk patients, facilitating the development of preventive
      medicine for this disease.

PMID- 27699268
TI  - Paneth cell defects in Crohn's disease patients promote dysbiosis.
AB  - BACKGROUND: Paneth cell dysfunction has been implicated in a subset of Crohn's
      disease (CD) patients. We previously stratified clinical outcomes of CD patients
      by using Paneth cell phenotypes, which we defined by the intracellular
      distribution of antimicrobial proteins. Animal studies suggest that Paneth cells
      shape the intestinal microbiome. However, it is unclear whether Paneth cell
      phenotypes alter the microbiome complexity in CD subjects. Therefore, we analyzed
      the correlation of Paneth cell phenotypes with mucosal microbiome composition and
      ileal RNA expression in pediatric CD and noninflammatory bowel disease (non-IBD)
      patients. METHODS: Pediatric CD (n = 44) and non-IBD (n = 62) patients aged 4 to
      18 were recruited prior to routine endoscopic biopsy. Ileal mucosal samples were
      analyzed for Paneth cell phenotypes, mucosal microbiome composition, and RNA
      transcriptome. RESULTS: The prevalence of abnormal Paneth cells was higher in
      pediatric versus adult CD cohorts. For pediatric CD patients, those with abnormal
      Paneth cells showed significant changes in their ileal mucosal microbiome,
      highlighted by reduced protective microbes and enriched proinflammatory microbes.
      Ileal transcriptome profiles showed reduced transcripts for genes that control
      oxidative phosphorylation in CD patients with abnormal Paneth cells. These
      transcriptional changes in turn were correlated with specific microbiome
      alterations. In non-IBD patients, a subset contained abnormal Paneth cells.
      However, this subset was not associated with alterations in the microbiome or
      host transcriptome. CONCLUSION: Paneth cell abnormalities in human subjects are
      associated with mucosal dysbiosis in the context of CD, and these changes are
      associated with alterations in oxidative phosphorylation, potentially in a
      feedback loop. FUNDING: The research was funded by Helmsley Charitable Trust (to
      T.S. Stappenbeck, R.J. Xavier, and D.P.B. McGovern), Crohn's and Colitis
      Foundation of America (to N.H. Salzman, T.S. Stappenbeck, R.J. Xavier, and C.
      Huttenhower), and Doris Duke Charitable Foundation grant 2014103 (to T.C. Liu).

PMID- 27699270
TI  - Asfotase alfa therapy for children with hypophosphatasia.
AB  - Background. Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of
      the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase
      (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase
      activity leads to extracellular accumulation of inorganic pyrophosphate, a
      natural substrate of TNSALP and inhibitor of mineralization. Children with HPP
      can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and
      premature deciduous tooth loss. Asfotase alfa is a recombinant, bone-targeted,
      human TNSALP injected s.c. to treat HPP. In 2012, we detailed the 1-year efficacy
      of asfotase alfa therapy for the life-threatening perinatal and infantile forms
      of HPP. Methods. Here, we evaluated the efficacy and safety of asfotase alfa
      treatment administered to children 6-12 years of age at baseline who were
      substantially impaired by HPP. Two radiographic scales quantitated HPP skeletal
      disease, including comparisons to serial radiographs from similarly affected
      historical control patients. Results. Twelve children receiving treatment were
      studied for 5 years. The 6-month primary endpoint was met, showing significant
      radiographic improvement. Additional significant improvements included patient
      growth, strength, motor function, agility, and quality of life, which for most
      patients meant achieving normal values for age- and sex-matched peers that were
      sustained at 5 years of treatment. For most, pain and disability resolved. Mild
      to moderate injection-site reactions were common and were sometimes associated
      with lipohypertrophy. Low anti-asfotase alfa antibody titers were noted in all
      patients. No evidence emerged for clinically important ectopic calcification or
      treatment resistance. Conclusions. Asfotase alfa enzyme replacement therapy has
      substantial and sustained efficacy with a good safety profile for children
      suffering from HPP. Trial Registration. ClinicalTrials.gov NCT00952484
      (https://clinicaltrials.gov/ct2/show/NCT00952484) and NCT01203826
      (https://clinicaltrials.gov/ct2/show/NCT01203826). Funding. Alexion
      Pharmaceuticals Inc. and Shriners Hospitals for Children.

PMID- 27699269
TI  - CRIg-expressing peritoneal macrophages are associated with disease severity in
      patients with cirrhosis and ascites.
AB  - Infections are an important cause of morbidity and mortality in patients with
      decompensated cirrhosis and ascites. Hypothesizing that innate immune dysfunction
      contributes to susceptibility to infection, we assessed ascitic fluid macrophage
      phenotype and function. The expression of complement receptor of the
      immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and
      functionally distinct peritoneal macrophage subpopulations. The proportion of
      CRIghi macrophages differed between patients and in the same patient over time,
      and a high proportion of CRIghi macrophages was associated with reduced disease
      severity (model for end-stage liver disease) score. As compared with CRIglo
      macrophages, CRIghi macrophages were highly phagocytic and displayed enhanced
      antimicrobial effector activity. Transcriptional profiling by RNA sequencing and
      comparison with human macrophage and murine peritoneal macrophage expression
      signatures highlighted similarities among CRIghi cells, human macrophages, and
      mouse F4/80hi resident peritoneal macrophages and among CRIglo macrophages, human
      monocytes, and mouse F4/80lo monocyte-derived peritoneal macrophages. These data
      suggest that CRIghi and CRIglo macrophages may represent a tissue-resident
      population and a monocyte-derived population, respectively. In conclusion,
      ascites fluid macrophage subset distribution and phagocytic capacity is highly
      variable among patients with chronic liver disease. Regulating the numbers and/or
      functions of these macrophage populations could provide therapeutic opportunities
      in cirrhotic patients.

PMID- 27699271
TI  - TGF-beta and VEGF cooperatively control the immunotolerant tumor environment and
      the efficacy of cancer immunotherapies.
AB  - Tregs imprint an early immunotolerant tumor environment that prevents effective
      antitumor immune responses. Using transcriptomics of tumor tissues, we identified
      early upregulation of VEGF and TGF-beta pathways compatible with tolerance
      imprinting. Silencing of VEGF or TGF-beta in tumor cells induced early and
      pleiotropic modulation of immune-related transcriptome signatures in tumor
      tissues. These were surprisingly similar for both silenced tumors and related to
      common downstream effects on Tregs. Silencing of VEGF or TGF-beta resulted in
      dramatically delayed tumor growth, associated with decreased Tregs and myeloid
      derived suppressor cells and increased effector T cell activation in tumor
      infiltrates. Strikingly, co-silencing of TGF-beta and VEGF led to a substantial
      spontaneous tumor eradication rate and the combination of their respective
      inhibitory drugs was synergistic. VEGF and/or TGF-beta silencing also restored
      tumor sensitivity to tumor-specific cell therapies and markedly improved the
      efficacy of anti-PD-1/anti-CTLA-4 treatment. Thus, TGF-beta and VEGF
      cooperatively control the tolerant environment of tumors and are targets for
      improved cancer immunotherapies.

PMID- 27699272
TI  - Effects of sphingosine-1-phosphate receptor 1 phosphorylation in response to
      FTY720 during neuroinflammation.
AB  - Fingolimod (FTY720, Gilenya), a sphingosine-1-phosphate receptor (S1PR)
      modulator, is one of the first-line immunomodulatory therapies for treatment of
      relapsing-remitting multiple sclerosis (MS). Human S1PR1 variants have been
      reported to have functional heterogeneity in vitro, suggesting that S1PR1
      function may influence FTY720 efficacy. In this study, we examined the influence
      of S1PR1 phosphorylation on response to FTY720 in neuroinflammation. We found
      that mice carrying a phosphorylation-defective S1pr1 gene [S1PR1(S5A) mice] were
      refractory to FTY720 treatment in MOG35-55-immunized and Th17-mediated
      experimental autoimmune encephalomyelitis (EAE) models. Long-term treatment with
      FTY720 induced significant lymphopenia and suppressed Th17 response in the
      peripheral immune system via downregulating STAT3 phosphorylation in both WT and
      S1PR1(S5A) mice. However, FTY720 did not effectively prevent neuroinflammation in
      the S1PR1(S5A) EAE mice as a result of encephalitogenic cells expressing C-C
      chemokine receptor 6 (CCR6). Combined treatment with FTY720 and anti-CCR6 delayed
      disease progression in S1PR1(S5A) EAE mice, suggesting that CCR6-mediated cell
      trafficking can overcome the effects of FTY720. This work may have translational
      relevance regarding FTY720 efficacy in MS patients and suggests that cell type
      specific therapies may enhance therapeutic efficacy in MS.

PMID- 27699273
TI  - CNS-directed gene therapy for the treatment of neurologic and somatic
      mucopolysaccharidosis type II (Hunter syndrome).
AB  - Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal storage disease
      characterized by severe neurologic and somatic disease caused by deficiency of
      iduronate-2-sulfatase (IDS), an enzyme that catabolizes the glycosaminoglycans
      heparan and dermatan sulphate. Intravenous enzyme replacement therapy (ERT)
      currently constitutes the only approved therapeutic option for MPSII. However,
      the inability of recombinant IDS to efficiently cross the blood-brain barrier
      (BBB) limits ERT efficacy in treating neurological symptoms. Here, we report a
      gene therapy approach for MPSII through direct delivery of vectors to the CNS.
      Through a minimally invasive procedure, we administered adeno-associated virus
      vectors encoding IDS (AAV9-Ids) to the cerebrospinal fluid of MPSII mice with
      already established disease. Treated mice showed a significant increase in IDS
      activity throughout the encephalon, with full resolution of lysosomal storage
      lesions, reversal of lysosomal dysfunction, normalization of brain transcriptomic
      signature, and disappearance of neuroinflammation. Moreover, our vector also
      transduced the liver, providing a peripheral source of therapeutic protein that
      corrected storage pathology in visceral organs, with evidence of cross-correction
      of nontransduced organs by circulating enzyme. Importantly, AAV9-Ids-treated
      MPSII mice showed normalization of behavioral deficits and considerably prolonged
      survival. These results provide a strong proof of concept for the clinical
      translation of our approach for the treatment of Hunter syndrome patients with
      cognitive impairment.

PMID- 27699274
TI  - B cells from African American lupus patients exhibit an activated phenotype.
AB  - Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease
      driven by both innate and adaptive immune cells. African Americans tend to
      present with more severe disease at an earlier age compared with patients of
      European ancestry. In order to better understand the immunological differences
      between African American and European American patients, we analyzed the
      frequencies of B cell subsets and the expression of B cell activation markers
      from a total of 68 SLE patients and 69 normal healthy volunteers. We found that B
      cells expressing the activation markers CD86, CD80, PD1, and CD40L, as well as
      CD19+CD27-IgD- double-negative B cells, were enriched in African American
      patients vs. patients of European ancestry. In addition to increased expression
      of CD40L, surface levels of CD40 on B cells were lower, suggesting the engagement
      of the CD40 pathway. In vitro experiments confirmed that CD40L expressed by B
      cells could lead to CD40 activation and internalization on adjacent B cells. To
      conclude, these results indicate that, compared with European American patients,
      African American SLE patients present with a particularly active B cell
      component, possibly via the activation of the CD40/CD40L pathway. These data may
      help guide the development of novel therapies.

PMID- 27699277
TI  - Potential tree species for use in urban areas in temperate and oceanic climates.
AB  - This study aims to assess the potential of trees for integration in urban
      development by evaluating the damage caused by trees in relation to various tree
      characteristics. Tree damage to permeable pavement systems and other urban
      structures such as impermeable pavements, kerbs, roads, retaining walls,
      footpaths, walls and buildings were assessed to identify the most suitable trees
      for the urban environment. One hundred square sites of 100 m * 100 m were
      randomly selected in Greater Manchester for this representative example case
      study to demonstrate the assessment methodology. Among tree species in this
      study, Acer platanoides L. (Norway maple) occurred most frequently (17%); others
      were Tilia spp. L. (Lime; 16%), Fraxinus excelsior L. (common ash; 12%), Acer
      pseudoplatanus L. (sycamore; 10%) and Prunus avium L. (wild cherry; 8%). The
      study concludes that 44% of the damage was to impermeable pavements and 22% to
      permeable pavements. Other damage to structures included kerbs (19%), retaining
      walls (5%), footpaths (4%), roads (3%) and walls (3%). Concerning the severity of
      damage, 66% were moderate, 21% light and 19% severe. Aesculus hippocastanum L.
      (horse chestnut) caused the greatest damage (59%) expressed in percentage as a
      ratio of the tree number related to damage over the corresponding tree number
      that was found close to structures.

PMID- 27699278
TI  - Resolving spatiotemporal characteristics of the seasonal hypoxia cycle in shallow
      estuarine environments of the Severn River and South River, MD, Chesapeake Bay,
      USA.
AB  - The nature of emerging patterns concerning water quality stressors and the
      evolution of hypoxia within sub-estuaries of the Chesapeake Bay has been an
      important unresolved question among the Chesapeake Bay community. Elucidation of
      the nature of hypoxia in the tributaries of the Chesapeake Bay has important
      ramifications to the successful restoration of the Bay, since much of Bay states
      population lives within the watersheds of the tributaries. Very little to date,
      is known about the small sub-estuaries of the Chesapeake Bay due to limited
      resources and the difficulties in resolving both space and time dimensions on
      scales that are adequate to resolve this question. We resolve the spatio-temporal
      domain dilemma by setting up an intense monitoring program of water quality
      stressors in the Severn and South Rivers, MD. Volume rendered models were
      constructed to allow for a visual dissection of the water quality times series
      which illustrates the life cycle of hypoxia and anoxia at the mid to upper
      portions of the tidal tributaries. The model also shows that unlike their larger
      Virginian tributary counterparts, there is little to no evidence of severe
      hypoxic water intrusions from the main-stem of the Chesapeake Bay into these sub
      estuaries.

PMID- 27699276
TI  - PRL3-zumab, a first-in-class humanized antibody for cancer therapy.
AB  - Novel, tumor-specific drugs are urgently needed for a breakthrough in cancer
      therapy. Herein, we generated a first-in-class humanized antibody (PRL3-zumab)
      against PRL-3, an intracellular tumor-associated phosphatase upregulated in
      multiple human cancers, for unconventional cancer immunotherapies. We focused on
      gastric cancer (GC), wherein elevated PRL-3 mRNA levels significantly correlated
      with shortened overall survival of GC patients. PRL-3 protein was overexpressed
      in 85% of fresh-frozen clinical gastric tumor samples examined but not in patient
      matched normal gastric tissues. Using human GC cell lines, we demonstrated that
      PRL3-zumab specifically blocked PRL-3+, but not PRL-3-, orthotopic gastric
      tumors. In this setting, PRL3-zumab had better therapeutic efficacy as a
      monotherapy, rather than simultaneous combination with 5-fluorouracil or 5
      fluorouracil alone. PRL3-zumab could also prevent PRL-3+ tumor recurrence.
      Mechanistically, we found that intracellular PRL-3 antigens could be externalized
      to become "extracellular oncotargets" that serve as bait for PRL3-zumab binding
      to potentially bridge and recruit immunocytes into tumor microenvironments for
      killing effects on cancer cells. In summary, our results document a comprehensive
      cancer therapeutic approach to specific antibody-targeted therapy against the PRL
      3 oncotarget as a case study for developing antibodies against other
      intracellular targets in drug discovery.

PMID- 27699275
TI  - Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer.
AB  - Radiation therapy (RT), a critical modality in the treatment of lung cancer,
      induces direct tumor cell death and augments tumor-specific immunity. However,
      despite initial tumor control, most patients suffer from locoregional relapse
      and/or metastatic disease following RT. The use of immunotherapy in non-small
      cell lung cancer (NSCLC) could potentially change this outcome by enhancing the
      effects of RT. Here, we report significant (up to 70% volume reduction of the
      target lesion) and durable (up to 12 weeks) tumor regressions in conditional Kras
      driven genetically engineered mouse models (GEMMs) of NSCLC treated with
      radiotherapy and a programmed cell death 1 antibody (alphaPD-1). However, while
      alphaPD-1 therapy was beneficial when combined with RT in radiation-naive tumors,
      alphaPD-1 therapy had no antineoplastic efficacy in RT-relapsed tumors and
      further induced T cell inhibitory markers in this setting. Furthermore, there was
      differential efficacy of alphaPD-1 plus RT among Kras-driven GEMMs, with
      additional loss of the tumor suppressor serine/threonine kinase 11/liver kinase
      B1 (Stk11/Lkb1) resulting in no synergistic efficacy. Taken together, our data
      provide evidence for a close interaction among RT, T cells, and the PD-1/PD-L1
      axis and underscore the rationale for clinical combinatorial therapy with immune
      modulators and radiotherapy.

PMID- 27699280
TI  - PTB and TIAR binding to insulin mRNA 3'- and 5'UTRs; implications for insulin
      biosynthesis and messenger stability.
AB  - OBJECTIVES: Insulin expression is highly controlled on the posttranscriptional
      level. The RNA binding proteins (RBPs) responsible for this result are still
      largely unknown. METHODS AND RESULTS: To identify RBPs that bind to insulin mRNA
      we performed mass spectrometry analysis on proteins that bound synthetic
      oligonucloetides mimicing the 5'- and the 3'-untranslated regions (UTRs) of rat
      and human insulin mRNA in vitro. We observed that the RBPs heterogeneous nuclear
      ribonucleoprotein (hnRNP) U, polypyrimidine tract binding protein (PTB), hnRNP L
      and T-cell restricted intracellular antigen 1-related protein (TIA-1-related
      protein; TIAR) bind to insulin mRNA sequences, and that the in vitro binding
      affinity of these RBPs changed when INS-1 cells were exposed to glucose, 3
      isobutyl-1-methylxanthine (IBMX) or nitric oxide. High glucose exposure resulted
      in a modest increase in PTB and TIAR binding to an insulin mRNA sequence. The
      inducer of nitrosative stress DETAnonoate increased markedly hnRNP U and TIAR
      mRNA binding. An increased PTB to TIAR binding ratio in vitro correlated with
      higher insulin mRNA levels and insulin biosynthesis rates in INS-1 cells. To
      further investigate the importance of RNA-binding proteins for insulin mRNA
      stability, we decreased INS-1 and EndoC-betaH1 cell levels of PTB and TIAR by
      RNAi. In both cell lines, decreased levels of PTB resulted in lowered insulin
      mRNA levels while decreased levels of TIAR resulted in increased insulin mRNA
      levels. Thapsigargin-induced stress granule formation was associated with a
      redistribution of TIAR from the cytosol to stress granules. CONCLUSIONS: These
      experiments indicate that alterations in insulin mRNA stability and translation
      correlate with differential RBP binding. We propose that the balance between PTB
      on one hand and TIAR on the other participates in the control of insulin mRNA
      stability and utilization for insulin biosynthesis.

PMID- 27699279
TI  - Identification of Leukotoxin and other vaccine candidate proteins in a Mannheimia
      haemolytica commercial antigen.
AB  - Bovine Respiratory Disease is the most costly disease that affects beef and dairy
      cattle industry. Its etiology is multifactorial, arising from predisposing
      environmental stress conditions as well as the action of several different
      respiratory pathogens. This situation has hindered the development of effective
      control strategies. Although different type of vaccines are available, many
      currently marketed vaccines are based on inactivated cultures of the main viral
      and bacterial agents involved in this pathology. The molecular composition of
      commercial veterinary vaccines is a critical issue. The present work aims to
      define at the proteomic level the most relevant valence of a line of commercial
      respiratory vaccines widely used in Central and South America. Since Mannheimia
      haemolytica is responsible for most of the disease associated morbid-mortality,
      we focused on the main proteins secreted by this pathogen, in particular
      Leukotoxin A, its main virulence factor. By Western blot analysis and mass
      spectrometry, Leukotoxin A was identified as a major component of M. haemolytica
      culture supernatants. We also identified other ten M. haemolytica proteins,
      including outer membrane proteins, periplasmic transmembrane solute transporters
      and iron binding proteins, which are relevant to achieve protective immunity
      against the pathogen. This work allowed a detailed molecular characterization of
      this vaccine component, providing evidence of its quality and efficacy.
      Furthermore, our results contributed to the identification of several proteins of
      interest as subunit vaccine candidates.

PMID- 27699281
TI  - Greater variation in affect is associated with lower fasting plasma glucose.
AB  - BACKGROUND: Depression and bipolar illness are associated with a 2-3 fold
      increase in the prevalence of diabetes. However, it is unknown whether variation
      in mood affects glucose metabolism. The aim of this study was to assess whether
      changes in affect were related to fasting plasma glucose and glycated
      haemoglobin. METHODS: 379 men and 441 women who took part in the 2003 Health
      Survey for England and had valid data for GHQ12 and fasting blood glucose were
      included. Mood variability was assessed by the General Health Questionnaire 12
      (GHQ12). Fasting plasma glucose and glycated haemoglobin (HbA1c) were measured by
      standard laboratory methodology and their relationship to variability assessed
      using linear regression. RESULTS: There was a significant inverse relationship
      between fasting blood glucose, but not HbA1c, and variability score (R2 = 0.327,
      p = 0.02) after adjusting for sociodemographic factors, anthropometric
      measurements, lifestyle, and use of medication. CONCLUSION: This study has shown
      an inverse association between changes in affect and fasting plasma glucose. This
      unexpected finding suggests that the association between affect and glucose is
      more complex than previously thought. Fasting blood glucose may reflect the
      operation of homeostatic mechanisms that are disturbed in certain mental states
      and are associated, therefore, with altered risk of diabetes and related
      metabolic conditions. This may have implications for the management of those with
      such conditions and with mental disorders.

PMID- 27699283
TI  - Influence of clinical history on MRI interpretation of optic neuropathy.
AB  - BACKGROUND AND PURPOSE: Clinical history is known to influence interpretation of
      a wide range of radiologic examinations. We sought to evaluate the influence of
      the clinical history on MRI interpretation of optic neuropathy. MATERIALS AND
      METHODS: 107 consecutive orbital MRI scans were retrospectively reviewed by three
      neuroradiologists. The readers independently evaluated the coronal STIR sequence
      for optic nerve hyperintensity and/or atrophy (yes/no) and the coronal post
      contrast T1WI for optic nerve enhancement (yes/no). Readers initially evaluated
      the cases blinded to the clinical history. Following a two week washout period,
      readers again evaluated the cases with the clinical history provided. Inter
      reader and reader-clinical radiologist agreement was assessed using Cohen's
      simple kappa coefficient. RESULTS: Intra-reader agreement, without and with
      provision of clinical history, was 0.564-0.716 on STIR and 0.270-0.495 on post
      contrast T1WI. Inter-reader agreement was overall fair-moderate. On post-contrast
      T1WI, inter-reader agreement was significantly higher when the clinical history
      was provided (p = 0.001). Reader-clinical radiologist agreement improved with
      provision of the clinical history to the readers on both the STIR and post
      contrast T1WI sequences. CONCLUSIONS: In the MRI assessment of optic neuropathy,
      only modest levels of inter-reader agreement were achieved, even after provision
      of clinical history. Provision of clinical history improved inter-reader
      agreement, especially when assessing for optic nerve enhancement. These findings
      confirm the subjective nature of orbital MRI interpretation in cases of optic
      neuropathy, and point to the importance of an accurate clinical history. Of note,
      the accuracy of orbital MRI in the context of optic neuropathy was not assessed,
      and would require further investigation.

PMID- 27699282
TI  - Use of multiple picosecond high-mass molecular dynamics simulations to predict
      crystallographic B-factors of folded globular proteins.
AB  - Predicting crystallographic B-factors of a protein from a conventional molecular
      dynamics simulation is challenging, in part because the B-factors calculated
      through sampling the atomic positional fluctuations in a picosecond molecular
      dynamics simulation are unreliable, and the sampling of a longer simulation
      yields overly large root mean square deviations between calculated and
      experimental B-factors. This article reports improved B-factor prediction
      achieved by sampling the atomic positional fluctuations in multiple picosecond
      molecular dynamics simulations that use uniformly increased atomic masses by 100
      fold to increase time resolution. Using the third immunoglobulin-binding domain
      of protein G, bovine pancreatic trypsin inhibitor, ubiquitin, and lysozyme as
      model systems, the B-factor root mean square deviations (mean +/- standard error)
      of these proteins were 3.1 +/- 0.2-9 +/- 1 A2 for Calpha and 7.3 +/- 0.9-9.6 +/-
      0.2 A2 for Cgamma, when the sampling was done for each of these proteins over 20
      distinct, independent, and 50-picosecond high-mass molecular dynamics simulations
      with AMBER forcefield FF12MC or FF14SB. These results suggest that sampling the
      atomic positional fluctuations in multiple picosecond high-mass molecular
      dynamics simulations may be conducive to a priori prediction of crystallographic
      B-factors of a folded globular protein.

PMID- 27699284
TI  - Beyond waste: new sustainable fillers from fly ashes stabilization, obtained by
      low cost raw materials.
AB  - A sustainable economy can be achieved only by assessing processes finalized to
      optimize the use of resources. Waste can be a relevant source of energy thanks to
      energy-from-waste processes. Concerns regarding the toxic fly ashes can be solved
      by transforming them into resource as recycled materials. The commitment to
      recycle is driven by the need to conserve natural resources, reduce imports of
      raw materials, save landfill space and reduce pollution. A new method to
      stabilize fly ash from Municipal Solid Waste Incinerator (MSWI) at room
      temperature has been developed thanks to COSMOS-RICE LIFE+ project (www.cosmos
      rice.csmt.eu). This process is based on a chemical reaction that occurs properly
      mixing three waste fly ashes with rice husk ash, an agricultural by-product.
      COSMOS inert can replace critical raw materials (i.e. silica, fluorspar, clays,
      bentonite, antimony and alumina) as filler. Moreover the materials employed in
      the stabilization procedure may be not available in all areas. This paper
      investigates the possibility of substituting silica fume with corresponding
      condensed silica fume and to substitute flue-gas desulfurization (FGD) residues
      with low-cost calcium hydroxide powder. The removal of coal fly ash was also
      considered. The results will be presented and a possible substitution of the
      materials to stabilize fly ash will be discussed.

PMID- 27699285
TI  - Gamma-tubulin coordinates nuclear envelope assembly around chromatin.
AB  - The cytosolic role of gamma-tubulin as a microtubule organizer has been studied
      thoroughly, but its nuclear function is poorly understood. Here, we show that
      gamma-tubulin is located throughout the chromatin of demembranated Xenopus laevis
      sperm and, as the nucleus is formed, gamma-tubulin recruits lamin B3 and nuclear
      membranes. Immunodepletion of gamma-tubulin impairs X. laevis assembly of both
      the lamina and the nuclear membrane. During nuclear formation in mammalian cell
      lines, gamma-tubulin establishes a cellular protein boundary around chromatin
      that coordinates nuclear assembly of the daughter nuclei. Furthermore, expression
      of a gamma-tubulin mutant that lacks the DNA-binding domain forms chromatin-empty
      nuclear like structures and demonstrate that a constant interplay between the
      chromatin-associated and the cytosolic pools of gamma-tubulin is required and,
      when the balance between pools is impaired, aberrant nuclei are formed. We
      therefore propose that the nuclear protein meshwork formed by gamma-tubulin
      around chromatin coordinates nuclear formation in eukaryotic cells.

PMID- 27699286
TI  - Significant loss of sensitivity and specificity in the taxonomic classification
      occurs when short 16S rRNA gene sequences are used.
AB  - The classification performance of Kraken was evaluated in terms of sensitivity
      and specificity when using short and long 16S rRNA sequences. A total of 440,738
      sequences from bacteria with complete taxonomic classifications were downloaded
      from the high quality ribosomal RNA database SILVA. Amplicons produced (86,371
      sequences; 1450 bp) by virtual PCR with primers covering the V1-V9 region of the
      16S-rRNA gene were used as reference. Virtual PCRs of internal fragments V3-V4,
      V4-V5 and V3-V5 were performed. A total of 81,523, 82,334 and 82,998 amplicons
      were obtained for regions V3-V4, V4-V5 and V3-V5 respectively. Differences in
      depth of taxonomic classification were detected among the internal fragments. For
      instance, sensitivity and specificity of sequences classified up to subspecies
      level were higher when the largest internal fraction (V3-V5) was used (54.0 and
      74.6% respectively), compared to V3-V4 (45.1 and 66.7%) and V4-V5 (41.8 and
      64.6%) fragments. Similar pattern was detected for sequences classified up to
      more superficial taxonomic categories (i.e. family, order, class...). Results
      also demonstrate that internal fragments lost specificity and some could be
      misclassified at the deepest taxonomic levels (i.e. species or subspecies). It is
      concluded that the larger V3-V5 fragment could be considered for massive high
      throughput sequencing reducing the loss of sensitivity and sensibility.

PMID- 27699292
TI  - Preface.

PMID- 27699293
TI  - Computing and Collaborative Care.

PMID- 27699294
TI  - Health Informatics Standards: A View From Mid-America.

PMID- 27699295
TI  - The Requirements of an Electronic Medical Record to Suit all Clinical
      Disciplines.
AB  - The design of the electronic medical record is becoming increasingly
      sophisticated as techniques develop to improve the understanding of user
      requirements. Such techniques must develop as it becomes increasingly important
      to improve the use and uptake of such records. An outstanding question is whether
      the same electronic medical record can fulfil the requirements of users in
      different clinical disciplines. To evaluate such a requirement it is necessary to
      understand the different information management the needs of different clinical
      disciplines. Only once these differing needs are understood, will it become
      possible to consider whether a common record is feasible in terms of both data
      modelling and the user interface. This paper describes the move towards a better
      understanding of user requirements. It outlines the differences between the
      requirements of various disciplines and discusses the implications. It
      concentrates on the differences between the requirements for hospital specialists
      and family medicine as an example of the problems.

PMID- 27699296
TI  - Clinicians at Work: Sharing Care in the Information Age.

PMID- 27699297
TI  - Collaboration Technology for Rural Health-care.
AB  - Health-care is a collaborative endeavor involving a number of individuals and
      organizations with diverse perspectives. Computer-supported collaboration
      technologies have great potential to enable health-care providers to improve the
      quality of care provided to their patients. Such technologies have the potential
      to overcome barriers to quality health-care in the small, scattered populations
      of rural areas. Rapid changes in technology are making it more and more possible
      for collaborative telemedicine to be a part of the practice of medicine. The
      World Wide Web has amply demonstrated that the globe has shrunk and information
      from afar is a mere mouse click away. However, the ease with which information is
      accessed along with the potential disclosure and misuse of personal information
      has raised serious concerns about the ability to restrict such information to
      legitimate accesses by duly authorized health-care providers. The authors present
      their experience in developing a health-care collaboration facility, ARTEMIS,
      which enabled Web-based access to electronic medical records, and provide a
      vision of their experiment to provide secure telemedicine for rural health-care
      practitioners.

PMID- 27699298
TI  - Medical Informatics Education at the University of Manchester.
AB  - Manchester University offered the first full time, undergraduate Medical
      Informatics degree programme in the UK. The B.Sc. in Medical Informatics was
      conceived in 1992 and its first cohort of students, taking the three year
      version, graduated in 1996; those students taking the four year version of the
      undergraduate degree will graduate in July 1997. The paper describes our somewhat
      turbulent experience of the first four years, highlighting both the difficulties
      and successes of launching an inter-disciplinary degree. First, the story of the
      programme's development is given by way of an introduction and to establish a
      suitable context for describing the programme in more detail. Then, after
      presenting the aim and objectives of the programme, we describe the overall
      structure of the course, and reflect upon certain key issues for establishing
      Medical Informatics as a distinct, academic discipline.

PMID- 27699299
TI  - Health Informatics Training at the University of Missouri.
AB  - Health informatics training has a long tradition at the University of Missouri.
      The current program prepares future researchers for the rapidly changing field of
      health informatics. This paper describes the training program, the fellowships,
      the interdisciplinary strengths of the program, and representative projects.
      Research opportunities range from information analyses of basic medical sciences
      through development of clinical information systems to the evaluation of
      information systems. The informatics training program at the University of
      Missouri promotes evidence-based medical informatics and has a strong emphasis on
      the organizational aspects of successful information system implementation.

PMID- 27699301
TI  - Health and Clinical Management.

PMID- 27699300
TI  - Strategy for Medical Informatics Education at the University of Medicine and
      Pharmacy in Timisoara.
AB  - Our strategy for adapting a curriculum in medical informatics for medical
      students is presented. After a brief overview, some specific conditions are
      addressed, which account for some peculiarities of the objectives of our courses
      and of the design of the curriculum, including its integration in the overall
      medical curriculum. Some efforts concerning examinations and some specific
      educational tools are then discussed. The paper also deals with particular
      features concerning medical informatics education for dentistry and pharmacy
      students as well as for postgraduate courses, paying special attention to the
      doctoral level. Finally, future perspectives of medical informatics education are
      discussed. The paper does not present a list of successes and achievements. We
      had, and still have several difficulties (not always related to financial
      drawbacks), which required a particular approach; the word "strategy'; in the
      title is also meant to cover these aspects.

PMID- 27699302
TI  - Computer-Based Patient Records.

PMID- 27699303
TI  - Information Systems.

PMID- 27699304
TI  - Image and Signal Processing.

PMID- 27699305
TI  - Decision Support Systems.

PMID- 27699306
TI  - Collaborative Knowledge Processing.

PMID- 27699307
TI  - Education.

PMID- 27699309
TI  - Integration of Information for Patient Care.

PMID- 27699308
TI  - Preface.

PMID- 27699310
TI  - Clinical workstations: An architectural prespective.
AB  - The role of a clinical workstation is examined as an integral part of a larger,
      clinical information delivery and acquisition system. Different care scenarios
      and environmental factors influence the behavior of a workstation. The common
      functional components of a workstation are information resources, application
      logic and presentation. A workstation is successful when each of its components
      operates within an information architecture and contributes to meet user needs.
      New technologies to integrate and display information are making the workstation
      functions independent of the actual hardware and software platform.

PMID- 27699311
TI  - Multimedia Workstations: Electronic Assistants for Health-Care Professionals.
AB  - The increasing costs of health care and the economic reality has produced an
      interesting paradox for the health professional to perform more clinical work
      with fewer support personnel. Moreover, an explosion of the knowledge-base that
      underlies sound clinical care not only makes effective time management critical,
      but also knowledge management compelling. A multimedia workstation is an
      electronic assistant for the busy health professional that can help with
      administrative tasks and give access to clinical information and knowledge
      networks. The multimedia nature of processed information reflects an evolution of
      medical technologies that involve more and more complex objects such as video
      sequences or digitized signals. Analysis of the 445 Medline-indexed publications
      for the January 1991 to December 1994 period, that included the word
      "workstation" either in their title or in their abstract, helps in refining
      objectives and challenges both for health professionals and decision makers. From
      an engineering perspective, development of a workstation requires the integration
      into the same environments of tools to localize, access, manipulate and
      communicate the required information. The long-term goal is to establish an easy
      access in a collaborative working environment that gives the end-user the feeling
      of a single virtual health enterprise, driven by an integrated computer system
      when the information system relies on a set of heterogeneous and geographically
      distributed components. Consequences in terms of migration from traditional
      client/server architectures to more client/network architectures are considered.

PMID- 27699312
TI  - Constructing Workstation Applications: Component Integration Strategies for a
      Changing Health-Care System.
AB  - A health-care workstation is the means by which a professional interacts with the
      information artifacts of health care. However, a major transformation is taking
      place in the software architecture of health-care systems that alters
      significantly the role of the workstation. Health-care systems are becoming more
      complex in response to the need to support "extended enterprises" across regions,
      and provide both horizontal and vertical integration capabilities. Component
      based software methodologies are being introduced that match well the needs of
      these large systems and the component services they must integrate. In the
      component-based framework, a workstation functions less as a "portal" for
      information transactions carried out on distant host computers, and more as the
      "orchestrator" for tasks involved in assembling, organizing, presenting, and
      manipulating information. Applications residing on workstations access
      distributed software components that carry out encapsulated functions for the
      application. Component-integration methodologies include both formal and ad hoc
      approaches; the principal emerging technologies are the World Wide Web (WWW),
      CORBA, Java, OLE, and OpenDoc. An emerging strategy appears to be that of
      developing application integration environments that encompass and support all of
      these integration methodologies. Component-based approaches also facilitate
      standardization at the message level, as messages to classes of components can
      serve to focus such standardization.

PMID- 27699313
TI  - Medical Images in Integrated Health Care Workstations.
AB  - The difference between an invention and a discovery is discussed, before turning
      to the sources of medical images. Next, the ongoing integration of image
      modalities in clinical routine is reviewed, as well as improvements in diagnosis
      and therapy planning with the help of better images in inter-connected
      distributed systems. Current shortcomings of image processing, and the attempts
      to overcome these shortcomings are presented. Examples of image processing are
      given, together with a vision on future systems and procedures.

PMID- 27699315
TI  - Trends in Integrated Clinical Workstations.
AB  - During the last decade, several projects aiming at integrated clinical
      workstations have been described and several prototypes have been demonstrated.
      In most of these projects, the clinical workstation accesses information and
      functionality provided by the present proprietary legacy systems of health-care
      institutions. We discuss trends in integrated clinical workstations from the
      viewpoints of software engineering and integration, considering that the clinical
      workstation itself basically consists of three layers: a presentation layer, a
      data integration layer, and a communication layer. The software engineering view
      on clinical workstations focuses on the development of basic building blocks from
      which clinical workstations, specific to a particular medical domain, can be
      composed. The integration view on clinical workstations addresses methods and
      techniques to deal with the, in general, intrinsically closed information systems
      in health-care institutions.

PMID- 27699316
TI  - The Education in Medical Informatics.

PMID- 27699314
TI  - An Information Mediator Network for Tasks in Dynamic Environments.
AB  - Coordination of activities among information workers and services, tracking and
      managing activities, and intelligent distribution of information are essential to
      the efficient operation of any large enterprise. This is particularly important
      in the healthcare domain, where many different organizations must cooperate to
      provide patient care reliably in a dynamically changing environment. In this
      review paper we present a distributed system that supports cooperative problem
      solving, activity management, and intelligent delivery of information in dynamic
      and unreliable environments. The system consists of a network of task/context
      managers (TCMs). Each TCM manages a group of related agents. It maintains up-to
      date information on availability, operational status, and activities of
      participating agents, and it acts as a mediator between service requesters and
      service providers. In addition, the TCM acts as a representative for its agents
      with other TCMs, allowing different groups of agents to collaborate with one
      another. This paper describes the system architecture, its implementation and
      capabilities including matchmaking, plan monitoring, and failure recovery. Our
      system has been used in prehospital emergency patient information management
      applications.

PMID- 27699317
TI  - Integrating Informatics into the Undergraduate Curriculum: A Report on a Pilot
      Project.
AB  - Previous case reports in this series on Education and Training have looked at
      specialist courses for postgraduate students seeking an in-depth knowledge of
      informatics and a career in the field. By contrast, this review describes a
      project designed to pilot a series of learning opportunities for undergraduate
      medical students. Although some UK medical colleges have opted to introduce
      informatics into the curriculum as a discipline in its own right, the Informatics
      Department at St Bartholomew's Hospital Medical College chose a different
      approach. When a new curriculum was introduced at St Bartholomew's and at The
      London Hospital Medical College, the Head of the Informatics Department saw this
      as an ideal opportunity to explore ways of integrating informatics into the
      curriculum. The initiatives described in this paper were made possible as a
      result of an award from the UK government Department of Employment. Money from an
      Enterprise in Higher Education grant funded a range of programmes, one of which
      was designed to introduce students to selected aspects of informatics and to
      demonstrate what is feasible in the undergraduate curriculum. The work carried
      out over a period of three and a half years was intended to provide the basis for
      the next phase of curriculum development. However, in the wake of the
      restructuring which has taken place in London medical colleges, the Informatics
      Department at what was St Bartholomew's has relocated to University College
      London Medical School, and is now called The Centre for Health Informatics and
      Multiprofessional Education (CHIME). University College is designing a new
      medical curriculum and CHIME is drawing on the experience gained through the
      Enterprise Project to find the best way to integrate informatics into this
      curriculum.

PMID- 27699318
TI  - Medical Informatics Training at Yale University School of Medicine.
AB  - The Yale Center for Medical Informatics has offered Medical Informatics training
      since 1986. The paper describes the overall structure of the training program,
      focusing primarily on the postdoctoral fellowship, a major component of which
      involves an independent project which the fellow carries out under faculty
      supervision. The paper outlines a number of areas in which such projects have
      been performed, describes the previous backgrounds and post-training career
      directions of the trainees, and discusses certain observations based on our
      experience with the program.

PMID- 27699319
TI  - Opportunities for Training in Biomedical Informatics at Vanderbilt University.

PMID- 27699321
TI  - Health and Clinical Management.

PMID- 27699320
TI  - Health Informatics at the University Of Victoria.
AB  - The University of Victoria has the only program in Canada offering a Bachelor of
      Science degree in Health Information Science. To meet the requirements of the
      degree, students must complete 60 units of course work (normally 40 courses) and
      4 CO-OP work terms over 4.3 years. The School admits approximately 30 students
      each year. Seventy-five percent of the students come from British Columbia,
      ranging in age from 18 to 50 years with the average age being 26 years. In
      addition to recent high school graduates, over 40% have previous degrees or
      diplomas, and 65% have over 5 years of work experience. The School's teaching
      team consists of 4 full-time faculty, 2 professional staff, 2 clerical staff, 7
      adjunct faculty and a variable number of sessional teaching staff. The majority
      of the faculty have health backgrounds, totalling 150 person-years of health care
      experience. As of November 1995, the School had 168 graduates 75% of whom are
      employed in British Columbia, 17% in other parts of Canada and 8% outside the
      country. Sixty-five percent of the graduates work in government departments
      including community health agencies; 10% work in hospitals, 20% work for
      management consulting firms, software houses, or computer hardware firms, and 5%
      are otherwise employed. Almost 100% of the graduates are gainfully employed in
      professional positions in which their health information science degree is
      valued. They work as systems analysts, system designers/developers, consultants,
      research assistants, health-care planners, information system-support
      staff/trainers and client-account representatives. Some are already in senior
      management positions.

PMID- 27699323
TI  - Biomedical Information Systems.

PMID- 27699322
TI  - Computer-based Patient Records.

PMID- 27699324
TI  - Image and Signal Processing.

PMID- 27699325
TI  - Decision-Support Systems.

PMID- 27699326
TI  - Knowledge Processing.

PMID- 27699327
TI  - Recent Advances in Computer Technologies and Medical Education.

PMID- 27699329
TI  - Access to Knowledge.

PMID- 27699330
TI  - Health Informatics and the Internet.

PMID- 27699328
TI  - Diagnosis and management of immune thrombocytopenia in childhood.
AB  - Evidence-based medicine is growing in immune thrombocytopenia (ITP), but solid
      clinical data are still lacking in many areas. A majority of children has self
      limited ITP, but chronic symptomatic ITP exists also in pediatrics. Management
      includes a watch-and-wait strategy for children with newly diagnosed ITP and no
      or mild bleeding, and immunoglobulins and corticosteroids, if more bleeding and
      mucous membrane involvement is present. Treatment endpoints differ in clinical
      research and in clinical practice. The requirement of platelet enhancing drugs
      needs to be better defined in guidelines. Second-line therapies for children are
      rarely required and include thrombopoietin-receptor agonists, rituximab,
      dexamethasone and immunosuppressants. Thrombopoietin-receptor agonists are
      successful in adult but also in pediatric ITP. The strategical position of
      splenectomy differs from that in adults. Although effective in children it is
      less frequently used because of its life-long cumulative risk of infectious
      diseases and a higher potential of spontaneous remission in ITP, providing a
      strong argument to defer splenectomy. The rarity of ITP makes clinical research
      expensive.

PMID- 27699331
TI  - Medical Informatics Training and Research at Rennes University School of
      Medicine.
AB  - The University of Rennes Medical School has offered Medical informatics training
      since 1988; at the same time, research in medical informatics was started. This
      paper describes the teaching programs at both the undergraduate level and at the
      graduate level. Research topics comprise fundamental research on biomedical
      models, ontologies for medical knowledge representations, natural language
      processing, and research for diagnosis and therapeutic aids. We have developed a
      local area network which communicates between the School of Medicine and the
      University Hospital, both internally (Intranet) and externally by access to the
      National Research network (RENATER) in France, which is connected to the
      internet.

PMID- 27699332
TI  - Health Informatics and Health Management Education at Central Queensland
      University.
AB  - Health informatics education is relatively new in Australia. It began at Central
      Queensland University in the early 1990s with the development of postgraduate
      programs in health administration and information systems. The University has a
      long tradition of distance education. The adoption of this approach for our
      combined health informatics and management courses enabled program delivery to
      students located anywhere in Australia and beyond. This paper describes course
      development and planned future developments.

PMID- 27699333
TI  - The Medical Informatics Program at the National University of Singapore.
AB  - The Medical Informatics Program at the National University of Singapore was
      established in September 1996 with a $4 million joint funding from the National
      Science and Technology Board and the Ministry of Education. The primary aims of
      the research program are to undertake upstream basic research in medical
      informatics and to build a critical mass of medical informatics expertise to meet
      long-term research goals and to effect technology transfer to the health sector
      of Singapore. Research projects fall into five groups: Clinical Decision Systems,
      Health Information Systems, Biomedical Datamining Systems, Medical Education
      Systems and Medical Networking, Applications Development and Integration Systems.

PMID- 27699334
TI  - Health Informatics Education and Research at the University of Athens.
AB  - In Europe, coordinated activities in healthcare informatics education started in
      the late 1980s with the establishment of European courses in health telematics.
      At the same time the European Commission foresaw the need for spreading the
      knowledge of Information Technology (IT) in the healthcare sector. Therefore the
      EC, since then, has supported the initiatives that aim to create awareness,
      stimulate diffusion, and educated and train the users (healthcare professionals)
      in the application of IT in health care [I]. Initiatives, such as the NIGHTINGALE
      project, are essential for the planning and implementation of strategies for
      training the nursing profession in using and applying healthcare information
      systems. Other projects are the IT EDUCTRA project, which is a practical project
      in the field of education and training of healthcare professionals in information
      technologies, and the ERASMUS Master's Course, which aims at giving those working
      (or intending to work) in the health service and related activities, a broad,
      advanced postgraduate education in health informatics.

PMID- 27699335
TI  - Medical Informatics and Telemedicine at the Politecnico di Milano.
AB  - Research and training programs in Medical Informatics and Telemedicine offered at
      the Politecnico di Milano are summarized. The educational pathways refer to the
      programs of: the (5-years) LaureaDegree, the (3-years) Diploma Universitario
      Degree, the post-Laurea (3-years) Doctoral Degree, the (I-year) Master's Degree,
      and a Continuing Education Program. The research programs focus on databases and
      extend to optimization of the "Visible Human Dataset-Milano Mirror Site"
      services. Additional activities relate to standardization at both the Italian and
      European levels, and to cooperation with hospitals and manufacturers.

PMID- 27699336
TI  - Current Status of the World Health Card Systems.
AB  - The perspective of our health card project has progressively changed from that of
      a pilot within a local environment (hospital, practice, community, etc.) to a
      large and national dimension. The interest of the many actors involved in health
      cards (healthcare authorities, insurance companies, social security agencies,
      standardization bodies, manufacturers, system integrators, etc.) is focusing
      increasingly on the role that the health card may have as an enabling component
      within the global communication and information system that will interconnect all
      points of care and services in a national healthcare system.

PMID- 27699337
TI  - Finding Medical Resources on the Internet.
AB  - As in every other segment of the Internet, the amount of health-care information
      has increased exponentially in the past five years. Research-oriented, clinical
      oriented and education-oriented medical resources have been built on the Internet
      by companies and institutions. Thousands of major medical web sites are currently
      serving millions of documents on the Internet, which are likely to double in the
      next 20 months. While the Internet is becoming the largest medical information
      repository, it is necessary that health-care professionals know efficient ways to
      find what they want in the vast field of medical information. This paper
      discusses the categorization, searching mechanisms and the impact of medical
      resources on the Internet.

PMID- 27699338
TI  - Networks: The "Fabric of Life" for Informatics Applications.

PMID- 27699339
TI  - Health and Clinical Management.

PMID- 27699340
TI  - Computer-based Patient Records.

PMID- 27699342
TI  - Intelligent Signal and Image Processing.

PMID- 27699341
TI  - Information Systems.

PMID- 27699343
TI  - Decision Support Systems and Knowledge Processing.

PMID- 27699345
TI  - Patient-centered Systems.

PMID- 27699344
TI  - Health and Medical Informatics Education.

PMID- 27699347
TI  - Managing Clinical Knowledge for Health Care Improvement.

PMID- 27699346
TI  - Patient-centered Systems.

PMID- 27699348
TI  - Patient-Computer Dialogue: A Review.
AB  - Since the first study of communication between patient and computer was performed
      at the University of Wisconsin in 1965, programs for patient-computer dialogue
      have been developed, implemented, and studied in numerous settings in the United
      States and abroad, and the results have been encouraging. This review presents a
      brief history of patient-computer dialogue together with suggested guidelines for
      programs in the future.

PMID- 27699349
TI  - Patient-centered Information Systems.
AB  - Patient-centered information systems augment traditional approaches to health
      information management with specific functions designed to support patient
      participation in health care decision making and treatment activities. In
      addition to computer-based record systems and business management applications,
      patient-centered information systems must include functionality that support
      communication between clinician and patient, and that provide information and
      peer support in a timely fashion to the patient. Current progress in information
      systems demonstrates the existence and feasibility of consumer health
      informatics, patient access to computerized clinical records, and technical and
      organizational solutions to integrating computerized patient information systems.
      We are now proposing a model of patient-centered system that incorporates all
      those components, and provides a vision of the future.

PMID- 27699351
TI  - Medical Informatics Research and Training at the Lister Hill National Center for
      Biomedical Communications.

PMID- 27699350
TI  - Electronic Healthcare Records: an essential part of Health Telematics
      Applications.
AB  - A healthcare record should ideally be a repository of data, describing a person's
      health and how it is being supported; and not, as it is now, describing a
      person's diseases and treatment only. The healthcare record is the basis for
      monitoring and decisions. Therefore it should be open and available to all
      authorized health professionals and to the patient. To make this easier is one of
      the major advantages of electronic healthcare records (EHCR). The computer-based
      patient record could make major contributions to improving the healthcare system.
      This is the motivation to initiatives, projects and routine implementations of
      electronic patient records. The European Union and national initiatives have put
      major efforts into the support of this main field of medical information
      processing.

PMID- 27699352
TI  - Education and Research at the Department of Medical Informatics Maastricht.

PMID- 27699353
TI  - Biomdecial and Health Informatics Research and Education at the University of
      Washington.
AB  - Although an extensive medical informatics research program as well as courses and
      training experiences in biomedical informatics have existed at the University of
      Washington (UW) for many years, a formal home did not exist until 1997 when the
      Division of Biomedical Informatics was created in the Department of Medical
      Education, School of Medicine. Since that time the expansion of the research,
      service and teaching programs has been rapid with a key milestone being a
      university commitment to provide funding, space and faculty to support the
      development of a new graduate program in Biomedical and Health Informatics.
      Hallmarks of the biomedical and health informatics program at the University of
      Washington include: - Strong shared belief that informatics research can
      contribute to the improvement of healthcare and health; - Large,
      multidisciplinary faculty including faculty from computer science, library and
      information science as well as the health sciences schools (dentistry, medicine,
      nursing, pharmacy, and public health and community medicine); - Comprehensive
      research and development partnership with the University of Washington Medical
      Centers information systems group and the UW Primary Care Network to move
      research from the laboratory to operational clinical systems; - Extensive and
      diverse regional setting in which to study information needs and develop
      informatics solutions in primary care settings; - Lack of barriers to
      interdisciplinary research and teaching.

PMID- 27699354
TI  - Research at the Department of Medical Informatics, Statistics and Documentation
      of the University of Graz.
AB  - The Department of Medical Informatics, Statistics and Documentation of the
      University of Graz has a double responsibility: research in medical informatics,
      and implementation and operation of information systems in the hospital. Research
      is therefore application oriented with emphasis on departmental information
      systems, image management, and information integration. Other topics include
      analysis of the preconditions for the acceptance and successful use of
      information systems in medicine, and the ethics and professional responsibility
      of medical informatics.

PMID- 27699356
TI  - Health and Clinical Management.

PMID- 27699355
TI  - Twenty Five Years of Medical Informatics Education at Heidelberg/Heilbronn:
      Discussion of a Specialized Curriculum for Medical Informatics.
AB  - The specialized university curriculum for medical informatics (MI) at the
      University of Heidelberg/School of Technology Heilbronn is one of the oldest
      educational approaches in the field of medical informatics, and has been
      successful for 25 years with about 1,000 graduates (Diplom-lnformatikerin der
      Medizin or Diplomlnformatiker der Medizin). It belongs to the category of
      dedicated master's programs for medical informatics and is based on the concept
      of medical informatics as a medical discipline in its own right. The curriculum
      is oriented towards the total spectrum of medical informatics ranging from health
      care economics, biosignal and medical image processing, medical documentation, to
      information and knowledge processing in medicine. It is a 4.5-year program with
      strong emphasis on the methodological foundations of medical informatics and on
      practical education in a number of specific laboratories. Thirty-five students
      are admitted each semester, and in total about 440 students are enrolled. The
      faculty consists of 17 full-time members and about 25 parttime lecturers.We
      report on characteristics, structure and contents of the new 5th version of the
      curriculum and discuss the features of a specialized curriculum for medical
      informatics with respect to the challenges for medical informatics in the 21st
      century.

PMID- 27699357
TI  - Changing the paradigm for Computer-based Patient Records.

PMID- 27699358
TI  - Integrated Information Systems.

PMID- 27699359
TI  - Image and Signal Processing.

PMID- 27699361
TI  - Education.

PMID- 27699360
TI  - Decision Support Systems and Knowledge Processing.

PMID- 27699362
TI  - Preface.

PMID- 27699363
TI  - The Promise of Medical Informatics.

PMID- 27699364
TI  - A Time of Change for Medical Informatics in the USA.

PMID- 27699365
TI  - The Promise of Medical Informatics in Europe.

PMID- 27699367
TI  - Reasoning Foundations of Medical Diagnosis Revisited. (Reflections on R.S.
      Ledley's paper: Reasoning Foundations of Medical Diagnosis).

PMID- 27699366
TI  - The Promise of Medical Informatics in Asia.

PMID- 27699368
TI  - Sequential Diagnosis by Computer. (Reflections on G.A. Gorry and G.O. Barnett's
      paper: Sequential Diagnosis by Computer).

PMID- 27699369
TI  - A Comment on the Help-System: A Program for Medical Decision Making from Early
      1970s. (Reflections on H. Warner et al.'s paper: HELP - A Program for Medical
      Decision-Making).

PMID- 27699370
TI  - A Convenient Framework for Health and Medical Decision-Making Processess
      (Reflections on S.G. Pauker's paper: Therapeutic Decision Making). (Reflections
      on S.G. Pauker's paper: Therapeutic Decision Making).

PMID- 27699371
TI  - Computer-Aided Diagnosis of Abdominal Pain. (Reflections on F.T. De Dombal et
      al.'s paper: Computer-Aided Diagnosis of Acute Abdominal Pain).

PMID- 27699373
TI  - The Promises and Perils of Modelling Medical Reasoning. (Reflections on E.H.
      Shortliffe and B.G. Buchanan's paper: A model of Inexact Reasoning in Medicine).

PMID- 27699372
TI  - Postscript on the Non-Perfectibility of Man. (Reflections on C.J. McDonald's
      paper: Protocol-based Computer Reminders, the Quality of Care and the Non
      Perfectability of Man).

PMID- 27699374
TI  - Diagnostic Support: Towards the Intelligent Integrated Reference Source.
      (Reflections on R.A. Miller et al.'s paper: INTERNIST-1: An experimental computer
      based diagnostic consultant for general internal medicine).

PMID- 27699375
TI  - The Birth of Automatic ECG Screening by Digital Electronic Computer. (Reflections
      on H.V. Pipberger et al.'s paper: Automatic Screening of Normal and Abnormal
      Electrocardiograms by Means of a Digital Electronic Computer).

PMID- 27699376
TI  - Reflections on Robb's paper: Dynamic Three-Dimensional X-Ray Computed Tomography
      of Heart, Lungs, and Circulation.

PMID- 27699377
TI  - What has Changed after Dr. Lawrence Weed's paper in 1968? (Reflections on L.L.
      Weed's paper: Medical Records that Guide and Teach).

PMID- 27699378
TI  - Medical and Health Information Systems; the Boundaries are Still Fading.
      (Reflections on M.F. Collen's paper: General Requirements for a Medical
      Information System).

PMID- 27699379
TI  - SNOMED - A Step Toward the Electronic Health Record. (Reflections on F.A. Cote's
      paper: The SNOP - SNOMED concept: Evolution towards common medical nomenclature
      and classification).

PMID- 27699380
TI  - Evaluation of a Field Test of Computers for the Doctor's Office. (Reflections on
      P.L. Reichertz et al.'s paper: Evaluation of a Field Test of Computers for the
      Doctor's Office).

PMID- 27699381
TI  - The Added Value of the EMR. (Reflections on G.O. Barnett's paper: COSTAR - A
      Computer-Based Medical Information System for Ambulatory Care).

PMID- 27699382
TI  - The Need for a Philosophy of Medical Informatics. (Reflections on F. Gremy's
      paper: The Future of Medical Informatics).

PMID- 27699383
TI  - The Theoretical Basis of Medical Information Science. (Reflections on Marsden S.
      Blois' paper on the proper use of man and machines).

PMID- 27699384
TI  - Health and Clinical Management.

PMID- 27699385
TI  - Computer-Based Patient Records.

PMID- 27699387
TI  - Image and Signal Processing.

PMID- 27699386
TI  - Information Systems.

PMID- 27699388
TI  - Knowledge Processing and Decision Support Systems.

PMID- 27699389
TI  - Data Linkage Strategies to Advance Youth Suicide Prevention: A Systematic Review
      for a National Institutes of Health Pathways to Prevention Workshop.
AB  - Background: Linking national, state, and community data systems to data from
      prevention programs could allow for longer-term assessment of outcomes and
      evaluation of interventions to prevent suicide. Purpose: To identify and describe
      data systems that can be linked to data from prevention studies to advance youth
      suicide prevention research. Data Sources: A systematic review, an environmental
      scan, and a targeted search were conducted to identify prevention studies and
      potentially linkable external data systems with suicide outcomes from January
      1990 through December 2015. Study Selection: Studies and data systems had to be
      U.S.-based and include persons aged 25 years or younger. Data systems also had to
      include data on suicide, suicide attempt, or suicidal ideation. Data Extraction:
      Information about participants, intervention type, suicide outcomes, primary
      analytic method used for linkage, statistical approach, analyses performed, and
      characteristics of data systems was abstracted by 2 reviewers. Data Synthesis: Of
      47 studies (described in 59 articles) identified in the systematic review, only 6
      were already linked to data systems. A total of 153 unique and potentially
      linkable data systems were identified, but only 66 were classified as "fairly
      accessible" and had data dictionaries available. Of the data systems identified,
      19% were established primarily for research, 11% for clinical care or operations,
      29% for administrative services (such as billing), and 52% for surveillance.
      About one third (37%) provided national data, 12% provided regional data, 63%
      provided state data, and 41% provided data below the state level (some provided
      coverage for >1 geographic unit). Limitation: Only U.S.-based studies published
      in English were included. Conclusion: There is untapped potential to evaluate and
      enhance suicide prevention efforts by linking suicide prevention data with
      existing data systems. However, sparse availability of data dictionaries and lack
      of adherence to standard data elements limit this potential. Primary Funding
      Source: Agency for Healthcare Research and Quality.

PMID- 27699390
TI  - Multiplexed fluorescence mediated tomography with temporal and spectral data.
AB  - We recently developed an algorithm for multiplexed fluorescence tomographic
      imaging of at least four fluorophores concurrently in the red and near-infrared
      wavelength region by jointly using spectral and temporal data. We report the
      design of a fluorescence tomography instrument that acquires spectral and
      temporal data, and validate its use in tissue-mimicking phantoms with four
      embedded fluorescent targets with highly overlapped spectral signatures.
      Critically, this requires measurement or computation of extended fluorophore
      signature libraries, which capture the variability in the measured signal due to
      the unknown position of the targets in the media. We demonstrate that we can
      demix and tomographically image all four fluorophores with zero image cross-talk,
      and 1 mm or better spatial resolution.

PMID- 27699391
TI  - Euglycemic Ketoacidosis Caused by Sodium-Glucose Cotransporter 2 Inhibitors: A
      Case Report.

PMID- 27699392
TI  - Long-Term Health Outcomes in Women With Silicone Gel Breast Implants.

PMID- 27699393
TI  - Long-Term Health Outcomes in Women With Silicone Gel Breast Implants.

PMID- 27699394
TI  - Should We Abandon Routine Visits?

PMID- 27699395
TI  - Should We Abandon Routine Visits?

PMID- 27699396
TI  - Should We Abandon Routine Visits?

PMID- 27699397
TI  - Should We Abandon Routine Visits?

PMID- 27699398
TI  - Should We Abandon Routine Visits?

PMID- 27699399
TI  - Should We Screen for Type 2 Diabetes?: Grand Rounds Discussion From Beth Israel
      Deaconess Medical Center.
AB  - The prevalence of diabetes in the United States is rising. Twelve percent of U.S.
      adults have diabetes and another 37% have impaired fasting glucose or impaired
      glucose tolerance. Diabetes is a major risk factor for such outcomes as
      cardiovascular disease, blindness, chronic kidney disease, and limb amputation.
      An important consideration is whether screening for abnormal glucose levels or
      diabetes reduces cardiovascular or all-cause morbidity and mortality. In October
      2015, the U.S. Preventive Services Task Force published recommendations on
      screening for abnormal blood glucose and concluded that intensive lifestyle
      interventions have a moderate benefit in reducing progression to diabetes in
      patients who have abnormal blood glucose levels detected by screening. It found
      inadequate evidence that such screening reduces cardiovascular or all-cause
      mortality and no evidence of psychological or other harms from screening. The
      Task Force recommends glucose screening every 3 years for adults aged 40 to 70
      years who are overweight or obese and do not have symptoms of diabetes. In this
      article, we present the case of a man who meets these criteria and explore his
      preferences and concerns regarding screening. Two experts then debate screening
      merits and benefits, the significance of abnormal blood glucose levels and
      diabetes as cardiovascular risk factors, and application of the guidelines to
      this particular patient.

PMID- 27699400
TI  - I Had to Get Cancer to Become a More Empathetic Doctor.

PMID- 27699401
TI  - Depression.
AB  - This issue provides a clinical overview of depression, focusing on screening,
      diagnosis, treatment, and practice improvement. The content of In the Clinic is
      drawn from the clinical information and education resources of the American
      College of Physicians (ACP), including MKSAP (Medical Knowledge and Self
      Assessment Program). Annals of Internal Medicine editors develop In the Clinic in
      collaboration with the ACP's Medical Education and Publishing divisions and with
      the assistance of additional science writers and physician writers.

PMID- 27699402
TI  - Web Exclusives. Annals Graphic Medicine - Today's Doctor-Patient Relationship.

PMID- 27699403
TI  - Correction: A Cost Analysis of the American Board of Internal Medicine's
      Maintenance-of-Certification Program.

PMID- 27699406
TI  - Report From the NEI/FDA Diabetic Retinopathy Clinical Trial Design and Endpoints
      Workshop.

PMID- 27699405
TI  - Paucibacterial Microbiome and Resident DNA Virome of the Healthy Conjunctiva.
AB  - Purpose: To characterize the ocular surface microbiome of healthy volunteers
      using a combination of microbial culture and high-throughput DNA sequencing
      techniques. Methods: Conjunctival swab samples from 107 healthy volunteers were
      analyzed by bacterial culture, 16S rDNA gene deep sequencing (n = 89), and biome
      representational in silico karyotyping (BRiSK; n = 80). Swab samples of the
      facial skin (n = 42), buccal mucosa (n = 50), and environmental controls (n = 27)
      were processed in parallel. 16S rDNA gene quantitative PCR was used to calculate
      the bacterial load in each site. Bacteria were characterized by site using
      principal coordinate analysis of metagenomics data. BRiSK data were analyzed for
      presence of fungi and viruses. Results: Corynebacteria, Propionibacteria, and
      coagulase-negative Staphylococci were the predominant organisms identified by all
      three techniques. Quantitative 16S PCR demonstrated approximately 0.1 bacterial
      16S rDNA/human actin copy on the ocular surface compared with greater than 10 16S
      rDNA/human actin copy for facial skin or the buccal mucosa. The conjunctival
      bacterial community structure is distinct compared with the facial skin (R =
      0.474, analysis of similarities P = 0.0001), the buccal mucosa (R = 0.893, P =
      0.0001), and environmental control samples (R = 0.536, P = 0.0001). 16S
      metagenomics revealed substantially more bacterial diversity on the ocular
      surface than other techniques, which appears to be artifactual. BRiSK revealed
      presence of torque teno virus (TTV) on the healthy ocular surface, which was
      confirmed by direct PCR to be present in 65% of all conjunctiva samples tested.
      Conclusions: Relative to adjacent skin or other mucosa, healthy ocular surface
      microbiome is paucibacterial. Its flora are distinct from adjacent skin. Torque
      teno virus is a frequent constituent of the ocular surface microbiome.
      (ClinicalTrials.gov number, NCT02298881.).

PMID- 27699409
TI  - Is Suppression Just Normal Dichoptic Masking? Suprathreshold Considerations.
AB  - Purpose: Amblyopic patients have a deficit in visual acuity and contrast
      sensitivity in their amblyopic eye as well as suppression of the amblyopic eye
      input under binocular viewing conditions. In this study we wanted to assess the
      origin of the amblyopic suppression by studying the contrast perception of the
      amblyopic eye at suprathreshold levels under binocular and monocular viewing.
      Methods: Using a suprathreshold contrast matching task in which the reference and
      target stimuli were presented to different eyes either simultaneously or
      successively, we measured interocular contrast matching in 10 controls and 11
      amblyopes (mean age 35 +/- 15; 5 strabismics; 3 anisometropes; 3 mixed). This was
      then used as an index of the binocular balance across spatial frequency and
      compared against the contrast sensitivity ratio measured with the same stimuli.
      Results: We observed that binocular matching becomes more imbalanced at high
      spatial frequency for amblyopes, compared with controls; that this imbalance did
      not depend in either group on whether the stimuli were presented simultaneously
      or successively; and that for both modes of presentation the matching balance
      correlates well with the interocular contrast sensitivity ratio (mean correlation
      coefficient of the slopes R = 0.7125). Conclusions: The results from our
      amblyopes show comparable losses of contrast perception at and above threshold
      under these binocular viewing conditions across a wide spatial frequency range,
      much stronger than that observed for our controls. This occurs under conditions
      in which there should be no dichoptic masking. Furthermore, the matching contrast
      could be well predicted by the monocular contrast sensitivity. Altogether, this
      suggests that amblyopic suppression cannot be explained by normal dichoptic
      masking but rather an attenuation of the input.

PMID- 27699407
TI  - In Vivo Brillouin Analysis of the Aging Crystalline Lens.
AB  - Purpose: To analyze the age dependence of the longitudinal modulus of the
      crystalline lens in vivo using Brillouin scattering data in healthy subjects.
      Methods: Brillouin scans were performed along the crystalline lens in 56 eyes
      from 30 healthy subjects aged from 19 to 63 years. Longitudinal elastic modulus
      was acquired along the sagittal axis of the lens with a transverse and axial
      resolution of 4 and 60 MUm, respectively. The relative lens stiffness was
      computed, and correlations with age were analyzed. Results: Brillouin axial
      profiles revealed nonuniform longitudinal modulus within the lens, increasing
      from a softer periphery toward a stiffer central plateau at all ages. The
      longitudinal modulus at the central plateau showed no age dependence in a range
      of 19 to 45 years and a slight decrease with age from 45 to 63 years. A
      significant intersubject variability was observed in an age-matched analysis.
      Importantly, the extent of the central stiff plateau region increased steadily
      over age from 19 to 63 years. The slope of change in Brillouin modulus in the
      peripheral regions were nearly age-invariant. Conclusions: The adult human lens
      showed no measurable age-related increase in the peak longitudinal modulus. The
      expansion of the stiff central region of the lens is likely to be the major
      contributing factor to age-related lens stiffening. Brillouin microscopy may be
      useful in characterizing the crystalline lens for the optimization of surgical or
      pharmacological treatments aimed at restoring accommodative power.

PMID- 27699408
TI  - Automated Quantification of Nonperfusion in Three Retinal Plexuses Using
      Projection-Resolved Optical Coherence Tomography Angiography in Diabetic
      Retinopathy.
AB  - Purpose: The purpose of this study was to evaluate an automated algorithm for
      detecting avascular area (AA) in optical coherence tomography angiograms (OCTAs)
      separated into three individual plexuses using a projection-resolved technique.
      Methods: A 3 * 3 mm macular OCTA was obtained in 13 healthy and 13 mild
      nonproliferative diabetic retinopathy (NPDR) participants. A projection-resolved
      algorithm segmented OCTA into three vascular plexuses: superficial, intermediate,
      and deep. An automated algorithm detected AA in each of the three plexuses that
      were segmented and in the combined inner-retinal angiograms. We assessed the
      diagnostic accuracy of extrafoveal and total AA using segmented and combined
      angiograms, the agreement between automated and manual detection of AA, and the
      within-visit repeatability. Results: The sum of extrafoveal AA from the segmented
      angiograms was larger in the NPDR group by 0.17 mm2 (P < 0.001) and detected NPDR
      with 94.6% sensitivity (area under the receiver operating characteristic curve
      [AROC] = 0.99). In the combined inner-retinal angiograms, the extrafoveal AA was
      larger in the NPDR group by 0.01 mm2 (P = 0.168) and detected NPDR with 26.9%
      sensitivity (AROC = 0.62). The total AA, inclusive of the foveal avascular zone,
      in the segmented and combined angiograms, detected NPDR with 23.1% and 7.7%
      sensitivity, respectively. The agreement between the manual and automated
      detection of AA had a Jaccard index of >0.8. The pooled SDs of AA were small
      compared with the difference in mean for control and NPDR groups. Conclusions: An
      algorithm to detect AA in OCTA separated into three individual plexuses using a
      projection-resolved algorithm accurately distinguishes mild NPDR from control
      eyes. Automatically detected AA agrees with manual delineation and is highly
      repeatable.

PMID- 27699410
TI  - Carbonic Anhydrase Inhibitors for the Treatment of Cystic Macular Lesions in
      Children With X-Linked Juvenile Retinoschisis.
AB  - Purpose: Little is known regarding the therapeutic effect of carbonic anhydrase
      inhibitors (CAIs) in the management of cystic macular lesions in children with X
      linked juvenile retinoschisis (XLRS) despite the fact that this disease often
      manifests during childhood. Therefore, our goal was to determine the efficacy of
      CAIs in the treatment of cystic macular lesions in children with XLRS. Methods:
      We used CAIs to treat cystic macular lesions in 18 eyes of nine children with
      XLRS. We evaluated the therapeutic effect of CAI treatment with the best
      corrected visual acuity and foveal zone thickness (FZT) with spectral-domain
      optical coherence tomography. A reduction of at least 22.4% in FZT was defined as
      objective evidence of response. Results: Five of nine (55.6%) XLRS patients
      showed a significant reduction of FZT in both eyes over a median treatment
      interval of 6.8 months (range, 1-23). In four of five (80.0%) patients, this
      reduction was already apparent after 1 month of treatment. An improvement of
      visual acuity was observed in five eyes (27.8%) of three patients (33.3%). Six
      patients (66.6%) reported minor side effects. Conclusions: Treatment with CAIs
      decreased FZT in more than half of the children with XLRS. This effect was
      observed within 1 month in the majority of patients. Carbonic anhydrase inhibitor
      treatment restores retinal anatomy and may contribute to creating optimal
      circumstances for gene therapy.

PMID- 27699411
TI  - Rapid, Dynamic Activation of Muller Glial Stem Cell Responses in Zebrafish.
AB  - Purpose: Zebrafish neurons regenerate from Muller glia following retinal lesions.
      Genes and signaling pathways important for retinal regeneration in zebrafish have
      been described, but our understanding of how Muller glial stem cell properties
      are regulated is incomplete. Mammalian Muller glia possess a latent neurogenic
      capacity that might be enhanced in regenerative therapies to treat degenerative
      retinal diseases. Methods: To identify transcriptional changes associated with
      stem cell properties in zebrafish Muller glia, we performed a comparative
      transcriptome analysis from isolated cells at 8 and 16 hours following an acute
      photic lesion, prior to the asymmetric division that produces retinal
      progenitors. Results: We report a rapid, dynamic response of zebrafish Muller
      glia, characterized by activation of pathways related to stress, nuclear factor
      kappaB (NF-kappaB) signaling, cytokine signaling, immunity, prostaglandin
      metabolism, circadian rhythm, and pluripotency, and an initial repression of Wnt
      signaling. When we compared publicly available transcriptomes of isolated mouse
      Muller glia from two retinal degeneration models, we found that mouse Muller glia
      showed evidence of oxidative stress, variable responses associated with immune
      regulation, and repression of pathways associated with pluripotency, development,
      and proliferation. Conclusions: Categories of biological processes/pathways
      activated following photoreceptor loss in regeneration-competent zebrafish Muller
      glia, which distinguished them from mouse Muller glia in retinal degeneration
      models, included cytokine signaling (notably NF-kappaB), prostaglandin E2
      synthesis, expression of core clock genes, and pathways/metabolic states
      associated with pluripotency. These regulatory mechanisms are relatively
      unexplored as potential mediators of stem cell properties likely to be important
      in Muller glial cells for successful retinal regeneration.

PMID- 27699412
TI  - Adipose-Derived Mesenchymal Stem Cells Reduce Lymphocytic Infiltration in a
      Rabbit Model of Induced Autoimmune Dacryoadenitis.
AB  - Purpose: To investigate the immunoregulatory roles of adipose-derived mesenchymal
      stem cells (ADSCs) in autoimmune dacryoadenitis. Methods: Rabbits were treated
      with ADSCs or phosphate-buffered solution on days 1, 3, 5, 7, and 9 after
      injection of activated peripheral blood lymphocytes, and clinical scores were
      determined by assessing tear production, break-up time, and fluorescein and
      hematoxylin and eosin staining. Inflammatory response was determined by measuring
      the expression of different mediators of inflammation in the lacrimal glands. The
      Th1/Th17-mediated autoreactive responses were evaluated by determining the
      proliferative response and the expression of cytokine genes and the lineage
      determining transcription factors. The frequency of regulatory T cells (Tregs)
      was also examined. Results: The ADSC-treated rabbits showed decreased autoimmune
      responses, and the secretory function of their lacrimal gland was restored
      significantly. Treatment with ADSCs downregulated the Th1 and Th17 responses but
      enhanced Tregs function. In addition, ADSC treatment noticeably suppressed the
      expression of matrix metalloproteinase (MMP)-9, MPP-2, IL-1beta, and IL-6,
      whereas it enhanced the expression of the anti-inflammatory cytokine IL-10.
      Conclusions: Our results demonstrated that ADSC administration efficiently
      ameliorates autoimmune dacryoadenitis mainly via modulating Th1/Th17 responses.

PMID- 27699413
TI  - On the Maintenance of Normal Ocular Dominance and a Possible Mechanism Underlying
      Refractive Adaptation.
AB  - Purpose: Do humans with uncorrected anisometropia who have not developed
      anisometropic amblyopia exhibit a shift in ocular dominance nonetheless,
      reflecting a more subtle form of deprivation? Also, is such a change in
      dominance, if it occurs, permanent or could it be rectified by an extended period
      of optical correction? Methods: A total of 25 normal controls (27.5 +/- 2.1
      years; mean +/- SD); 28 anisometropes (20.7 +/- 5.6 years) who were fully
      corrected for more than 16 weeks prior to this investigation; and 24
      anisometropes who had never been corrected (21.2 +/- 9.8 years) participated in
      this study. Sensory eye dominance of observers was measured using the binocular
      phase combination paradigm to find an interocular contrast ratio at which the
      contributions of each eye to the binocularly fused percept were equal (i.e., the
      balance point measure of ocular dominance). Results: Controls exhibited a balance
      point close to unity (0.91 +/- 0.05), while the two groups of anisometropes
      exhibited a clear binocular imbalance (uncorrected anisometropes, 0.51 +/- 0.28;
      corrected anisometropes, 0.70 +/- 0.19); both were significantly different from
      controls (P < 0.001). The imbalance was less severe in corrected anisometropes
      compared with uncorrected anisometropes (P = 0.004). Conclusions: We find that
      anisometropia is associated with an ocular imbalance even in the absence of
      amblyopia. This abnormality is weaker in anisometropes who have worn an optical
      correction for some time, suggestive that a better optical status leads to a
      better binocular status.

PMID- 27699414
TI  - Progression of Late-Onset Stargardt Disease.
AB  - Purpose: Identification of sensitive biomarkers is essential to determine
      potential effects of emerging therapeutic trials for Stargardt disease. This
      study aimed to describe the natural history of late-onset Stargardt, and
      demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression
      as an outcome measure. Methods: We performed a retrospective cohort study
      collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt,
      defined by clinical phenotype, at least one ABCA4 mutation, and age at disease
      onset >= 45 years. We analyzed RPE atrophy progression on fundus autofluorescence
      and near-infrared reflectance imaging using semiautomated software and a linear
      mixed model. We performed sample size calculations to assess the power in a
      simulated 2-year interventional study and assessed visual endpoints using time-to
      event analysis. Results: Over time, progression of RPE atrophy was observed
      (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only
      patients with bilateral RPE atrophy in a future trial, 32 patients are needed to
      reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect
      size of 30%. We found a median interval between disease onset and visual acuity
      decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI:
      6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. Conclusions: We
      show that RPE atrophy represents a robust biomarker to monitor disease
      progression in future therapeutic trials. In contrast, the variability in terms
      of the course of visual acuity was high.

PMID- 27699415
TI  - Diagnosing Sporadic Creutzfeldt-Jakob Disease by the Detection of Abnormal Prion
      Protein in Patient Urine.
AB  - Importance: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder
      associated with the accumulation of infectious abnormal prion protein through a
      mechanism of templated misfolding. A recent report has described the detection of
      abnormal prion protein in the urine of patients with variant CJD (vCJD) using
      protein misfolding by cyclic amplification, which was apparently absent in the
      more common sporadic form of CJD (sCJD). A noninvasive diagnostic test could
      improve early diagnosis of sCJD and, by screening donations, mitigate the
      potential risks of prion transmission through human urine-derived
      pharmaceuticals. Here, we describe the adaptation of the direct detection assay,
      developed originally as a blood test for vCJD, for the detection of disease
      associated prion protein in urine samples from patients with sCJD. Objective: To
      determine the feasibility of sCJD diagnosis by adaptation of an established vCJD
      diagnostic blood test to urine. Design, Setting, and Participants: This
      retrospective, cross-sectional study included anonymized urine samples from
      healthy nonneurological control individuals (n = 91), patients with non-prion
      neurodegenerative diseases (n = 34), and patients with prion disease (n = 37) of
      which 20 had sCJD. Urine samples obtained during the Medical Research Council
      PRION-1 Trial, the National Prion Monitoring Cohort Study, and/or referred to the
      National Prion Clinic or Dementia Research Centre at the National Hospital for
      Neurology and Neurosurgery in the United Kingdom. Main Outcomes and Measures:
      Presence of sCJD infection determined by an assay that captures, enriches, and
      detects disease-associated prion protein isoforms. Results: A total of 162
      samples were analyzed, composed of 91 normal control individuals (51 male, 33
      female, and 7 not recorded), 34 neurological disease control individuals (19 male
      and 15 female), and 37 with prion disease (22 male and 15 female). The assay's
      specificity for prion disease was 100% (95% CI, 97%-100%), with no false-positive
      reactions from 125 control individuals, including 34 from a range of
      neurodegenerative diseases. In contrast to a previous study, which used a
      different method, sensitivity to vCJD infection was low (7.7%; 95% CI, 0.2%-36%),
      with only 1 of 13 patients with positive test results, while sensitivity to sCJD
      was unexpectedly high at 40% (95% CI, 19%-64%). Conclusions and Relevance: We
      determined 40% of sCJD urine sample results as positive. To our knowledge, this
      is the first demonstration of an assay that can detect sCJD infection in urine or
      any target analyte outside of the central nervous system. Urine detection could
      allow the development of rapid, molecular diagnostics for sCJD and has
      implications for other neurodegenerative diseases where disease-related
      assemblies of misfolded proteins might also be present in urine.

PMID- 27699418
TI  - Reflections and Selections.

PMID- 27699417
TI  - National Institutes of Health Pathways to Prevention Workshop: Advancing Research
      to Prevent Youth Suicide.
AB  - The National Institutes of Health (NIH) Pathways to Prevention Workshop
      "Advancing Research to Prevent Youth Suicide" was cosponsored by the NIH Office
      of Disease Prevention, National Institute of Mental Health, National Institute on
      Drug Abuse, and National Center for Complementary and Integrative Health. A
      multidisciplinary working group developed the agenda, and an evidence-based
      practice center prepared an evidence report that addressed data systems relevant
      to suicide prevention efforts through a contract with the Agency for Healthcare
      Research and Quality. During the workshop, experts discussed the evidence and
      participants commented during open forums. After considering the data from the
      evidence report, expert presentations, and public comments, an independent panel
      prepared a draft report that was posted on the NIH Office of Disease Prevention
      Web site for 5 weeks for public comment. This abridged version of the final
      report provides a road map for optimizing youth suicide prevention efforts by
      highlighting strategies for guiding the next decade of research in this area.
      These strategies include recommendations for improving data systems, enhancing
      data collection and analysis methods, and strengthening the research and practice
      community.

PMID- 27699421
TI  - FDA-Approved Drugs to Treat Sleep Disorders.

PMID- 27699416
TI  - Specificity and timescales of cortical adaptation as inferences about natural
      movie statistics.
AB  - Adaptation is a phenomenological umbrella term under which a variety of temporal
      contextual effects are grouped. Previous models have shown that some aspects of
      visual adaptation reflect optimal processing of dynamic visual inputs, suggesting
      that adaptation should be tuned to the properties of natural visual inputs.
      However, the link between natural dynamic inputs and adaptation is poorly
      understood. Here, we extend a previously developed Bayesian modeling framework
      for spatial contextual effects to the temporal domain. The model learns temporal
      statistical regularities of natural movies and links these statistics to
      adaptation in primary visual cortex via divisive normalization, a ubiquitous
      neural computation. In particular, the model divisively normalizes the present
      visual input by the past visual inputs only to the degree that these are inferred
      to be statistically dependent. We show that this flexible form of normalization
      reproduces classical findings on how brief adaptation affects neuronal
      selectivity. Furthermore, prior knowledge acquired by the Bayesian model from
      natural movies can be modified by prolonged exposure to novel visual stimuli. We
      show that this updating can explain classical results on contrast adaptation. We
      also simulate the recent finding that adaptation maintains population
      homeostasis, namely, a balanced level of activity across a population of neurons
      with different orientation preferences. Consistent with previous disparate
      observations, our work further clarifies the influence of stimulus-specific and
      neuronal-specific normalization signals in adaptation.

PMID- 27699423
TI  - Suicide in Childhood.
AB  - Suicide by children younger than 11 is a sad and tragic occurrence. Indeed,
      suicidal ideation and behavior has been documented in children as young as ages 3
      to 7. The current overview provides a discussion of the frequency of suicide in
      children and associated predisposing conditions, such as depression and abuse. In
      response to these tragic events, nursing interventions are also proposed.
      [Journal of Psychosocial Nursing and Mental Health Services, 54(10), 27-30.].

PMID- 27699422
TI  - Methylene Blue: The Long and Winding Road From Stain to Brain: Part 2.
AB  - Methylene blue was the first synthetic drug ever used in medicine, having been
      used to treat clinical pain syndromes, malaria, and psychotic disorders more than
      one century ago. Methylene blue is a cationic thiazine dye with redox-cycling
      properties and a selective affinity for the nervous system. This drug also
      inhibits the activity of monoamine oxidase, nitric oxide synthase, and guanylyl
      cyclase, as well as tau protein aggregation; increases the release of
      neurotransmitters, such as serotonin and norepinephrine; reduces amyloid-beta
      levels; and increases cholinergic transmission. The action of methylene blue on
      multiple cellular and molecular targets justifies its investigation in various
      neuropsychiatric disorders. Investigations of methylene blue were instrumental in
      the serendipitous development of phenothiazine antipsychotic drugs. Although
      chlorpromazine is heralded as the first antipsychotic drug used in psychiatry,
      methylene blue is a phenothiazine drug that had been used to treat psychotic
      patients half a century earlier. It has also been studied in bipolar disorder and
      deserves further investigation for the treatment of unipolar and bipolar
      disorders. More recently, methylene blue has been the subject of preclinical and
      clinical investigations for cognitive dysfunction, dementia, and other
      neurodegenerative disorders. [Journal of Psychosocial Nursing and Mental Health
      Services, 54(10), 21-26.].

PMID- 27699424
TI  - Implementation of the Six Core Strategies for Restraint Minimization in a
      Specialized Mental Health Organization.
AB  - Implementation of the Six Core Strategies to Reduce the Use of Seclusion and
      Restraint (Six Core Strategies) at a recovery-oriented, tertiary level mental
      health care facility and the resultant changes in mechanical restraint and
      seclusion incidents are described. Strategies included increased executive
      participation; enhanced staff knowledge, skills, and attitudes; development of
      restraint orders and decision support in the electronic medical record to enable
      informed debriefing and tracking of events; and implementation of initiatives to
      include service users and their families in the plan of care. Strategies were
      implemented in a staged manner across 3 years. The total number of mechanical
      restraint and seclusion incidents decreased by 19.7% from 2011/12 to 2013/14.
      Concurrently, the average length of a mechanical restraint or seclusion incident
      decreased 38.9% over the 36-month evaluation period. Implementation of the Six
      Core Strategies for restraint minimization effectively decreased the number and
      length of mechanical restraint and seclusion incidents in a specialized mental
      health care facility. [Journal of Psychosocial Nursing and Mental Health
      Services, 54(10), 32-39.].

PMID- 27699425
TI  - Clinical Simulation in Psychiatric-Mental Health Nursing: Post-Graduation Follow
      Up.
AB  - In psychiatric-mental health, creating an innovative strategy to help students
      learn content that may not be frequently seen in a clinical setting is
      challenging. Thus, simulation helps narrow this gap. Using Kirkpatrick and
      Kirkpatrick's model of evaluation to guide the current study, faculty contacted
      baccalaureate nursing program graduates who completed a psychiatric-mental health
      clinical simulation scenario featuring a hanging suicide and wrist cutting
      suicide attempt scenario in the "Behind the Door" series as part of the clinical
      component of their undergraduate psychiatric-mental health course. Eleven nurses
      responded to a survey regarding their post-graduate encounters with these types
      of clinical situations, and their perception of recall and application of
      knowledge and skills acquired during the simulation experience to the clinical
      situation. Nursing graduates' responses are expressed through three major themes:
      emotional, contextual/behavioral, and assessment outcomes. Data from the survey
      indicate that nursing graduates perceived the "Behind the Door" simulations as
      beneficial to nursing practice. This perception is important in evaluating
      knowledge transfer from a simulation experience as a student into application in
      nursing practice. [Journal of Psychosocial Nursing and Mental Health Services,
      54(10), 40-45.].

PMID- 27699426
TI  - Psychotropic Alternatives to Antipsychotic Medications in Treating Dementia
      Behaviors: An Evidence-Based Practice Protocol.
AB  - Antipsychotic medications pose a significant risk to older adult patients with
      dementia and are frequently prescribed as first-line treatment for behaviors
      associated with dementia in skilled nursing facilities (SNFs). SNFs are often
      cited by the Centers for Medicare & Medicaid for inappropriate antipsychotic
      medication use. The purpose of the current article is to communicate an evidence
      based practice (EBP) clinical protocol that can guide clinicians away from
      prescribing antipsychotic medications in the treatment of dementia behaviors. A
      literature review of 17 rigorous research studies was conducted to determine
      psychotropic risk and efficacy in treating dementia behaviors. An EBP clinical
      protocol establishing a hierarchy of psychotropic medications based on risk and
      efficacy was developed to guide clinicians away from the use of antipsychotic
      medications and toward the use of potentially safer and more efficacious
      psychotropic medications in dementia treatment while offering flexibility for
      clinical judgment. [Journal of Psychosocial Nursing and Mental Health Services,
      54(10), 46-53.].

PMID- 27699428
TI  - How Do I Look?

PMID- 27699429
TI  - The Evolving Role of A Nurse Planner.
AB  - Nurse planner roles and responsibilities for educational activities have changed
      over time from the logistical management of an activity to completing
      documentation for contact hours to being a key player in the entire educational
      design process. This article explores the current expectations of a nurse planner
      for a continuing education activity. J Contin Educ Nurs. 2016;47(10):437-439.

PMID- 27699430
TI  - The Fall Season: A Time of Home, Holidays, and Health Literacy!
AB  - Health literacy is a priority issue, as the majority of American adults lack the
      skills needed to manage their health. Health literacy education and competencies
      should be incorporated throughout all nursing curricula, as nurses are uniquely
      positioned to enhance effective communication that is essential to patient safety
      and patient outcomes. J Contin Educ Nurs. 2016;47(10):440-442.

PMID- 27699431
TI  - Getting to the Root of Disparities: Social Cognition and the Affective Domain.
AB  - Bias, prejudice, cultural insensitivity, and eroding levels of empathy all affect
      the health and well being of patients and families and manifest or accelerate
      social disparities of health. For caregivers, educational offerings and
      activities targeting the affective domain can positively influence the
      development of greater empathy and improved social cognition. As difficult as it
      is to develop effective teaching methods for this domain, new strides in virtual
      reality technology and new research on implicit bias can provide the professional
      development educator with options in designing educational offerings that can
      help. J Contin Educ Nurs. 2016;47(10):443-445.

PMID- 27699432
TI  - Reduction of Clinical Culture Contamination in an Inpatient Medical Unit by
      Revisiting Microbiology Education.
AB  - Clinical culture contaminations delay the correct diagnosis, result in repeat
      testing, and may extend the length of a hospital stay. A simple educational
      session reminding providers of the ubiquitous presence of bacteria on the skin
      and in our environment, led to a significant decrease in contaminated cultures
      (16.9% versus 10.9%, p = 0.03). J Contin Educ Nurs. 2016;47(10):446-448.

PMID- 27699433
TI  - Interprofessional Teamwork Education: Moving Toward the Patient-Centered
      Approach.
AB  - : HOW TO OBTAIN CONTACT HOURS BY READING THIS ISSUE Instructions: 1.3 contact
      hours will be awarded by Villanova University College of Nursing upon successful
      completion of this activity. A contact hour is a unit of measurement that denotes
      60 minutes of an organized learning activity. This is a learner-based activity.
      Villanova University College of Nursing does not require submission of your
      answers to the quiz. A contact hour certificate will be awarded after you
      register, pay the registration fee, and complete the evaluation form online at
      http://goo.gl/gMfXaf. In order to obtain contact hours you must: 1. Read the
      article, "Interprofessional Teamwork Education: Moving Toward the Patient
      Centered Approach," found on pages 449-460, carefully noting any tables and other
      illustrative materials that are included to enhance your knowledge and
      understanding of the content. Be sure to keep track of the amount of time (number
      of minutes) you spend reading the article and completing the quiz. 2. Read and
      answer each question on the quiz. After completing all of the questions, compare
      your answers to those provided within this issue. If you have incorrect answers,
      return to the article for further study. 3. Go to the Villanova website to
      register for contact hour credit. You will be asked to provide your name, contact
      information, and a VISA, MasterCard, or Discover card number for payment of the
      $20.00 fee. Once you complete the online evaluation, a certificate will be
      automatically generated. This activity is valid for continuing education credit
      until September 30, 2019. CONTACT HOURS This activity is co-provided by Villanova
      University College of Nursing and SLACK Incorporated. Villanova University
      College of Nursing is accredited as a provider of continuing nursing education by
      the American Nurses Credentialing Center's Commission on Accreditation.
      OBJECTIVES Explain the recommended framework in teaching and implementing
      interprofessional competencies. Identify suggested core competencies to implement
      interprofessional collaborative practice. DISCLOSURE STATEMENT Neither the
      planners nor the author have any conflicts of interest to disclose. BACKGROUND:
      The aim of this study is to develop and contextualize a competency framework for
      interprofessional teamwork in Iran. METHOD: The study was conducted in three
      phases. First, the competencies of interprofessional teamwork were extracted from
      the literature. In the second phase, the content validity of the initial
      framework was assessed by the experts through the Delphi rounds. Content validity
      ratio (CVR) and item-level content validity index (I-CVI) were used for
      quantitative analysis. Finally, in the third phase, the importance and utility of
      interprofessional teamwork competencies were assessed by the experts. RESULTS:
      Initial framework was constructed with 28 competencies. Quantitative analysis by
      CVR indicated a score of less than .49 for three items. These items were excluded
      from the framework. The I-CVI for all items in the framework was higher than .78.
      The final framework was developed and validated with 16 competencies. DISCUSSION:
      The developed framework is recommended for teaching and assessment of
      interprofessional teamwork competencies. J Contin Educ Nurs. 2016;47(10):449-460.

PMID- 27699435
TI  - Development of a Web-Based Diabetes Education Program for Health Care
      Professionals.
AB  - This study developed a Web-based type 2 diabetes education program (WB-DEP) for
      health care professionals. The methodology consisted of a pretest-posttest quasi
      experimental approach. The study group consisted of 44 nurses and six midwives
      who volunteered for the study. The WB-DEP was developed in accordance with the
      effective teaching design model of Morrison, Ross, and Kemp. Data for the study
      were collected using the Information Form, The Section Evaluation Tests, the Web
      Based Teaching Material Evaluation Scale, and the WB-DEP Opinion Form. In the
      statistical evaluation of the data, the averages, percentages, frequencies, and
      mean values were calculated, and the Wilcoxon signed-rank test was also used.
      According to the results, the study group believed that the WB-DEP was generally
      useful, successful, beneficial, informative, and understandable. In addition, the
      WB-DEP was found to significantly increase participants' knowledge about
      diabetes. J Contin Educ Nurs. 2016;47(10):464-471.

PMID- 27699436
TI  - An Innovative Educational Approach to Reducing Catheter-Associated Urinary Tract
      Infections: A Case Study.
AB  - Best practices for urinary catheter insertion and care are well documented in the
      literature. However, the development of educational methods to address best
      practice standards has been relatively stagnant. A novel educational approach to
      teach practicing providers proper catheter insertion and care was developed under
      a blended learning model with online videos and hands-on simulations. The
      education was custom created for each participant role. This education also
      highlighted the providers' own hospitals' catheter-associated urinary tract
      infections (CAUTI) rates, the negative patient outcomes that have occurred as a
      result of CAUTIs, and the financial burdens caused by CAUTIs. Results showed a
      significant inverse relationship between whether the education was occurring and
      the number of monthly CAUTIs. The results provided evidence that engaging
      frontline workers in blended learning catheter care simulation education was
      significantly associated with a lower number of monthly CAUTIs. Other
      institutions can design similar educational interventions to reduce their CAUTI
      rates. J Contin Educ Nurs. 2016;47(10):473-476.

PMID- 27699437
TI  - Significant relationship between soil bacterial community structure and incidence
      of bacterial wilt disease under continuous cropping system.
AB  - Soil bacteria are very important in biogeochemical cycles and play significant
      role in soil-borne disease suppression. Although continuous cropping is
      responsible for soil-borne disease enrichment, its effect on tobacco plant health
      and how soil bacterial communities change are yet to be elucidated. In this
      study, soil bacterial communities across tobacco continuous cropping time-series
      fields were investigated through high-throughput sequencing of 16S ribosomal RNA
      genes. The results showed that long-term continuous cropping could significantly
      alter soil microbial communities. Bacterial diversity indices and evenness
      indices decreased over the monoculture span and obvious variations for community
      structures across the three time-scale tobacco fields were detected. Compared
      with the first year, the abundances of Arthrobacter and Lysobacter showed a
      significant decrease. Besides, the abundance of the pathogen Ralstonia spp.
      accumulated over the monoculture span and was significantly correlated with
      tobacco bacterial wilt disease rate. Moreover, Pearson's correlation demonstrated
      that the abundance of Arthrobacter and Lysobacter, which are considered to be
      beneficial bacteria had significant negative correlation with tobacco bacterial
      wilt disease. Therefore, after long-term continuous cropping, tobacco bacterial
      wilt disease could be ascribed to the alteration of the composition as well as
      the structure of the soil microbial community.

PMID- 27699438
TI  - The thnR gene is a negative transcription regulator of the thurincin H genetic
      cassette in Bacillus thuringiensis subsp. morrisoni.
AB  - Thurincin H is a bacteriocin synthesized by some strains of Bacillus
      thuringiensis. In this study, the thurincin H genetic cassette, which contains
      ten genes, from a Mexican strain of B. thuringiensis subsp. morrisoni (Btm) was
      cloned and sequenced. To study the function of the thnR gene component in the
      cassette, we generated various constructs with or without thnR for expression in
      Btm. All transformants harboring thnR in recombinant plasmids showed a decrease
      of ~15 to ~90 % in inhibitory activity against the target strain, Bacillus cereus
      183. Importantly, a ~90 % reduction in inhibition occurred with Btm harboring a
      construct containing thnR alone, suggesting that ThnR, indeed, functions as a
      negative transcription regulator of the thurincin H cassette. Based on sequence
      homology, ThnR was classified as a member of the YtrA subfamily of the GntR
      superfamily of transcriptional regulators.

PMID- 27699439
TI  - Historical perspective on the "discovery" of the anterolateral ligament of the
      knee.
AB  - : There is a lively debate about the existence, origins and discoverer of the
      anterolateral ligament of the knee. The complex anatomy of the lateral aspect of
      the knee has made it difficult to differentiate between various structures such
      as the iliotibial band, capsulo-osseous layer, Kaplan's fibres and the
      anterolateral capsule. The "discovery" of a new anterolateral structure in 2013
      was the culmination of many historical studies. In 1879, Paul Ferdinand Segond
      described a tibial plateau fracture in which he noted a pearly band reinforcing
      the joint capsule. Other anatomists had their suspicions about this ligament; it
      was described by Vallois in 1914 in his thesis and extensively studied by Jost in
      1921. References to it can be found in comparative anatomy studies. This
      historical review serves as a reminder that understanding and treating knee
      sprains is not something new. LEVEL OF EVIDENCE: V.

PMID- 27699440
TI  - Are milk and alternatives and fruit and vegetable intakes during adolescence
      associated with cortical and trabecular bone structure, density, and strength in
      adulthood?
AB  - : We investigated the impact of food group intake during adolescence on bone
      structure and strength during adulthood. In females, we found a beneficial effect
      of adolescent milk and alternatives and fruit and vegetable intake on adult
      radius shaft and distal tibia bone structure, respectively. No association was
      observed in males. INTRODUCTION: The purpose of this study was to investigate
      whether adolescents with high intake of milk and alternatives (M&A) or fruit and
      vegetables (F&V) had better adult bone structure and strength compared to those
      with low intake levels. METHODS: We analyzed data from 47 males and 69 females
      enrolled in the Pediatric Bone Mineral Accrual Study (PBMAS 1991-2011), who had
      one peripheral quantitative computed tomography scan at age 29 +/- 2 years. We
      measured radius and tibia shaft total area (ToA), cortical area (CoA), cortical
      content (CoC), cortical density, bone strength (SSIp), and muscle area, as well
      as distal radius and tibia ToA, total density, trabecular area, trabecular
      content, trabecular density, and bone strength (BSIc). Sequential 24-h recalls
      were used to assess M&A and F&V intake; participants were grouped for their mean
      intake during adolescence (low = bottom quartile, moderate = middle quartiles,
      high = top quartile) and were compared using multivariate analysis of covariance
      while adjusting for adult height, muscle area, physical activity, energy and
      calcium intake and adolescent energy intake, and physical activity. RESULTS:
      Females with high M&A intake compared to low M&A intake group (mean 3.8 vs. 1.3
      servings/day, respectively) had greater adult ToA (14 %, p < 0.05), CoA (15 %, p
      < 0.01), and CoC (16 %, p < 0.01) at radius shaft. Females with moderate F&V
      intake compared to low F&V intake group (mean 3.7 vs. 2.1 servings/day,
      respectively) had greater adult ToA (8.5 %, p < 0.05) at distal tibia.
      CONCLUSION: Higher intake of M&A or F&V during adolescence had a long-term
      beneficial effect on bone structure in females, an association not observed in
      males.

PMID- 27699441
TI  - Economic evaluation of osteoporosis liaison service for secondary fracture
      prevention in postmenopausal osteoporosis patients with previous hip fracture in
      Japan.
AB  - : A model-based cost-effectiveness analysis was performed to evaluate the cost
      effectiveness of secondary fracture prevention by osteoporosis liaison service
      (OLS) relative to no therapy in patients with osteoporosis and a history of hip
      fracture. Secondary fracture prevention by OLS is cost-effective in Japanese
      women with osteoporosis who have suffered a hip fracture. INTRODUCTION: The
      purpose of this study was to estimate, from the perspective of Japan's healthcare
      system, the cost-effectiveness of secondary fracture prevention by OLS relative
      to no therapy in patients with osteoporosis and a history of hip fracture.
      METHODS: A patient-level state transition model was developed to predict lifetime
      costs and quality-adjusted life years (QALYs) in patients with or without
      secondary fracture prevention by OLS. The incremental cost-effectiveness ratio
      (ICER) of secondary fracture prevention compared with no therapy was estimated.
      Sensitivity analyses were performed to examine the influence of parameter
      uncertainty on the base case results. RESULTS: Compared with no therapy,
      secondary fracture prevention in patients aged 65 with T-score of -2.5 resulted
      in an additional lifetime cost of $3396 per person and conferred an additional
      0.118 QALY, resulting in an ICER of $28,880 per QALY gained. Deterministic
      sensitivity analyses showed that treatment duration and offset time strongly
      affect the cost-effectiveness of OLS. According to the results of scenario
      analyses, secondary fracture prevention by OLS was cost-saving compared with no
      therapy in patients with a family history of hip fracture and high alcohol
      intake. CONCLUSIONS: Secondary fracture prevention by OLS is cost-effective in
      Japanese women with osteoporosis who have suffered a hip fracture. In addition,
      secondary fracture prevention is less expensive than no therapy in high-risk
      patients with multiple risk factors.

PMID- 27699442
TI  - Associations between autistic traits and fractional anisotropy values in white
      matter tracts in a nonclinical sample of young adults.
AB  - Whereas a number of studies have examined relationships among brain activity,
      social cognitive skills, and autistic traits, fewer studies have evaluated
      whether structural connections among brain regions relate to these traits and
      skills. Uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF) are
      white matter tracts that may underpin the behavioral expression of these skills
      because they connect regions within or provide sensory information to brain areas
      implicated in social cognition, and structural differences in these tracts have
      been associated with autistic traits. We examined relationships among self
      reported autistic traits, mentalizing, and water diffusivity in UF and ILF in a
      nonclinical sample of 24 young adults (mean age = 21.92 years, SD = 4.72 years;
      15 women). We measured autistic traits using the Autism-Spectrum Quotient, and we
      measured mentalizing using the Dynamic Interactive Shapes Clips task. We used
      Tract-Based Spatial Statistics and randomize to examine relationships among
      fractional anisotropy (FA) values in bilateral ILF and UF, age, cognitive
      abilities, autistic traits, and mentalizing. Autistic traits were positively
      related to FA values in left ILF. No other relationships between FA values and
      other variables were significant. Results suggest that left ILF may be involved
      in the expression of autistic traits in individuals without clinical diagnoses.

PMID- 27699443
TI  - A systematic review of possible serious adverse health effects of nicotine
      replacement therapy.
AB  - We conducted a systematic literature review to identify and critically evaluate
      studies of serious adverse health effects (SAHEs) in humans using nicotine
      replacement therapy (NRT) products. Serious adverse health effects refer to
      adverse events, leading to substantial disruption of the ability to conduct
      normal life functions. Strength of evidence evaluations and conclusions were also
      determined for the identified SAHEs. We evaluated 34 epidemiological studies and
      clinical trials, relating NRT use to cancer, reproduction/development, CVD,
      stroke and/or other SAHEs in patients, and four meta-analyses on effects in
      healthy populations. The overall evidence suffers from many limitations, the most
      significant being the short-term exposure (<=12 weeks) and follow-up to NRT
      product use in most of the studies, the common failure to account for changes in
      smoking behaviour following NRT use, and the sparse information on SAHEs by type
      of NRT product used. The only SAHE from NRT exposure we identified was an
      increase in respiratory congenital abnormalities reported in one study. Limited
      evidence indicated a lack of effect between NRT exposure and SAHEs for CVD and
      various reproduction/developmental endpoints. For cancer, stroke and other SAHEs,
      the evidence was inadequate to demonstrate any association with NRT use. Our
      conclusions agree with recent statements from authoritative bodies.

PMID- 27699444
TI  - The safety of nanostructured synthetic amorphous silica (SAS) as a food additive
      (E 551).
AB  - KEY MESSAGES: Particle sizes of E 551 products are in the micrometre range. The
      typical external diameters of the constituent particles (aggregates) are greater
      than 100 nm. E 551 does not break down under acidic conditions such as in the
      stomach, but may release dissolved silica in environments with higher pH such as
      the intestinal tract. E 551 is one of the toxicologically most intensively
      studied substances and has not shown any relevant systemic or local toxicity
      after oral exposure. Synthetic amorphous silica (SAS) meeting the specifications
      for use as a food additive (E 551) is and has always been produced by the same
      two production methods: the thermal and the wet processes, resulting in E 551
      products consisting of particles typically in the micrometre size range. The
      constituent particles (aggregates) are typically larger than 100 nm and do not
      contain discernible primary particles. Particle sizes above 100 nm are necessary
      for E 551 to fulfil its technical function as spacer between food particles, thus
      avoiding the caking of food particles. Based on an in-depth review of the
      available toxicological information and intake data, it is concluded that the SAS
      products specified for use as food additive E 551 do not cause adverse effects in
      oral repeated-dose studies including doses that exceed current OECD guideline
      recommendations. In particular, there is no evidence for liver toxicity after
      oral intake. No adverse effects have been found in oral fertility and
      developmental toxicity studies, nor are there any indications from in vivo
      studies for an immunotoxic or neurotoxic effect. SAS is neither mutagenic nor
      genotoxic in vivo. In intact cells, a direct interaction of unlabelled and
      unmodified SAS with DNA was never found. Differences in the magnitude of
      biological responses between pyrogenic and precipitated silica described in some
      in vitro studies with murine macrophages at exaggerated exposure levels seem to
      be related to interactions with cell culture proteins and cell membranes. The in
      vivo studies do not indicate that there is a toxicologically relevant difference
      between SAS products after oral exposure. It is noted that any silicon dioxide
      product not meeting established specifications, and/or produced to provide new
      functionality in food, requires its own specific safety and risk assessment.

PMID- 27699446
TI  - CALR-mutated primary myelofibrosis evolving to chronic myeloid leukemia with both
      CALR mutation and BCR-ABL1 fusion gene.

PMID- 27699445
TI  - CRISPR/Cas9 Immune System as a Tool for Genome Engineering.
AB  - CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR
      associated) adaptive immune systems constitute a bacterial defence against
      invading nucleic acids derived from bacteriophages or plasmids. This prokaryotic
      system was adapted in molecular biology and became one of the most powerful and
      versatile platforms for genome engineering. CRISPR/Cas9 is a simple and rapid
      tool which enables the efficient modification of endogenous genes in various
      species and cell types. Moreover, a modified version of the CRISPR/Cas9 system
      with transcriptional repressors or activators allows robust transcription
      repression or activation of target genes. The simplicity of CRISPR/Cas9 has
      resulted in the widespread use of this technology in many fields, including basic
      research, biotechnology and biomedicine.

PMID- 27699447
TI  - Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of
      viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid
      leukemia.
AB  - Intensive chemotherapy directed against acute myeloid leukemia of childhood is
      followed by profound neutropenia and high risk for bacterial and fungal
      infections, including viridans group streptococci as a common cause for gram
      positive septicemia. Few retrospective studies have shown the efficacy of various
      antibiotic prophylactic regimens in children. We retrospectively studied 50
      pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at
      St. Anna Children's Hospital and assessed the effect of antibiotic prophylaxis on
      the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric
      patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred
      after none of 98 cycles with prophylactic administration of
      teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79
      cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p < 0.0001). In
      addition, there were significantly fewer episodes of febrile neutropenia in the
      teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity
      of infection seemed to be worse when no antibiotic prophylaxis had been
      administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs.
      4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus
      isolates in surveillance cultures was noticed. Antibiotic prophylaxis with
      teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication
      of viridans sepsis and decreased incidence of febrile neutropenia in pediatric
      AML patients. The possibility to administer teicoplanin on alternate days on an
      outpatient basis or at home could contribute to patient's quality of life and
      decrease health care costs.

PMID- 27699448
TI  - M2 macrophages do not fly into a "RAGE".
AB  - Tumor-associated macrophages (TAMs) are key elements in orchestrating host
      responses inside tumor stroma. This population may undergo a polarized activation
      process, thus rendering a heterogeneous spectrum of phenotypes, where the
      classically activated type 1 macrophages (M1) and the alternative activated type
      2 macrophages (M2) represent two extreme phenotypes. In this commentary, based on
      very recent research findings, we intend to highlight how complex could be the
      crosstalk among all components of tumor stroma, where the coexistence of non
      natural partners may even skew the canonical responses that we can expect.

PMID- 27699449
TI  - Analysis of Pesticides and Toxic Heavy Metals Contained in Mosquito Coils.
AB  - In this study, 10 mosquito coils manufactured in China were obtained in Suriname,
      South America, where they are used extensively. The coils were analyzed for
      organics (allethrin, permethrin, and butylated hydroxytoluene) and heavy metals
      (Cr, Co, As, Cd, and Pb) by GC-MS and ICP-MS, respectively. Allethrin was the
      only target organic compound detected in all mosquito coils with concentrations
      ranging from ~1900 to ~4500 ug/g. The concentrations of heavy metals varied as
      follows (in ug/g): Cr: 2.9-9.4, Co: 0.1-1.2, Cu: 0.7-16.1, Se: 0.10-0.4, Ni: 2.1
      5.8, As: 0.10-2.2, Cd: 0.10-0.2, and Pb: 1.1-3.6.

PMID- 27699450
TI  - Analytical approaches for the characterization and quantification of
      nanoparticles in food and beverages.
AB  - Estimating consumer exposure to nanomaterials (NMs) in food products and
      predicting their toxicological properties are necessary steps in the assessment
      of the risks of this technology. To this end, analytical methods have to be
      available to detect, characterize and quantify NMs in food and materials related
      to food, e.g. food packaging and biological samples following metabolization of
      food. The challenge for the analytical sciences is that the characterization of
      NMs requires chemical as well as physical information. This article offers a
      comprehensive analysis of methods available for the detection and
      characterization of NMs in food and related products. Special attention was paid
      to the crucial role of sample preparation methods since these have been partially
      neglected in the scientific literature so far. The currently available
      instrumental methods are grouped as fractionation, counting and ensemble methods,
      and their advantages and limitations are discussed. We conclude that much
      progress has been made over the last 5 years but that many challenges still
      exist. Future perspectives and priority research needs are pointed out. Graphical
      Abstract Two possible analytical strategies for the sizing and quantification of
      Nanoparticles: Asymmetric Flow Field-Flow Fractionation with multiple detectors
      (allows the determination of true size and mass-based particle size
      distribution); Single Particle Inductively Coupled Plasma Mass Spectrometry
      (allows the determination of a spherical equivalent diameter of the particle and
      a number-based particle size distribution).

PMID- 27699451
TI  - Ciprofloxacin: pH-dependent SERS signal and its detection in spiked river water
      using LoC-SERS.
AB  - Monitoring the successful removal of antibiotics in waste and surface waters is
      of high interest to overcome the occurrence of antibacterial resistance in the
      ecosystem. Among the newly developed analytical methods, the lab-on-a-chip
      surface-enhanced Raman spectroscopic (LoC-SERS) technique has gained the interest
      of the scientific community in the last few years. Ciprofloxacin, a second
      generation fluoroquinolone, is widely used and administered to patients in
      dosages up to 1000 mg. In addition, more than 50 % of the antibiotic is excreted
      in urine as the parental drug. Thus, ciprofloxacin in environmental samples may
      exceed the minimum inhibitory concentration (MIC) values. The present study aims
      to assess the potential of the LoC-SERS technique to detect the target analyte in
      spiked river water samples at MIC concentrations. As sample clean-up procedure, a
      simple filtration is proposed, while as SERS, active substrates silver
      nanoparticles prepared at room temperature are employed. Ciprofloxacin was
      successfully quantified in the 0.7-10 MUM concentration range with data that were
      measured on two different days. Furthermore, because of the low solubility of the
      antibiotic at the neutral pH range, insights into the effect of pH on the SERS
      signal of the target molecule are also presented. Graphical Abstract
      Ciprofloxacin detected at MIC values by LOC-SERS.

PMID- 27699452
TI  - Architecture and functional properties of the CFTR channel pore.
AB  - The main function of the cystic fibrosis transmembrane conductance regulator
      (CFTR) is as an ion channel for the movement of small anions across epithelial
      cell membranes. As an ion channel, CFTR must form a continuous pathway across the
      cell membrane-referred to as the channel pore-for the rapid electrodiffusional
      movement of ions. This review summarizes our current understanding of the
      architecture of the channel pore, as defined by electrophysiological analysis and
      molecular modeling studies. This includes consideration of the characteristic
      functional properties of the pore, definition of the overall shape of the entire
      extent of the pore, and discussion of how the molecular structure of distinct
      regions of the pore might control different facets of pore function. Comparisons
      are drawn with closely related proteins that are not ion channels, and also with
      structurally unrelated proteins with anion channel function. A simple model of
      pore function is also described.

PMID- 27699453
TI  - Mechanosensor polycystin-1 potentiates differentiation of human osteoblastic
      cells by upregulating Runx2 expression via induction of JAK2/STAT3 signaling
      axis.
AB  - Polycystin-1 (PC1) has been proposed as a chief mechanosensing molecule
      implicated in skeletogenesis and bone remodeling. Mechanotransduction via PC1
      involves proteolytic cleavage of its cytoplasmic tail (CT) and interaction with
      intracellular pathways and transcription factors to regulate cell function. Here
      we demonstrate the interaction of PC1-CT with JAK2/STAT3 signaling axis in
      mechanically stimulated human osteoblastic cells, leading to transcriptional
      induction of Runx2 gene, a master regulator of osteoblastic differentiation.
      Primary osteoblast-like PC1-expressing cells subjected to mechanical-stretching
      exhibited a PC1-dependent increase of the phosphorylated(p)/active form of JAK2.
      Specific interaction of PC1-CT with pJAK2 was observed after stretching while pre
      treatment of cells with PC1 (anti-IgPKD1) and JAK2 inhibitors abolished JAK2
      activation. Consistently, mechanostimulation triggered PC1-mediated
      phosphorylation and nuclear translocation of STAT3. The nuclear
      phosphorylated(p)/DNA-binding competent pSTAT3 levels were augmented after
      stretching followed by elevated DNA-binding activity. Pre-treatment with a STAT3
      inhibitor either alone or in combination with anti-IgPKD1 abrogated this effect.
      Moreover, PC1-mediated mechanostimulation induced elevation of Runx2 mRNA levels.
      ChIP assays revealed direct regulation of Runx2 promoter activity by STAT3/Runx2
      after mechanical-stretching that was PC1-dependent. Our findings show that
      mechanical load upregulates expression of Runx2 gene via potentiation of PC1
      JAK2/STAT3 signaling axis, culminating to possibly control osteoblastic
      differentiation and ultimately bone formation.

PMID- 27699455
TI  - Tardive tachypnea.

PMID- 27699454
TI  - From the endoplasmic reticulum to the plasma membrane: mechanisms of CFTR folding
      and trafficking.
AB  - CFTR biogenesis starts with its co-translational insertion into the membrane of
      endoplasmic reticulum and folding of the cytosolic domains, towards the
      acquisition of a fully folded compact native structure. Efficiency of this
      process is assessed by the ER quality control system that allows the exit of
      folded proteins but targets unfolded/misfolded CFTR to degradation. If allowed to
      leave the ER, CFTR is modified at the Golgi and reaches the post-Golgi
      compartments to be delivered to the plasma membrane where it functions as a cAMP-
      and phosphorylation-regulated chloride/bicarbonate channel. CFTR residence at the
      membrane is a balance of membrane delivery, endocytosis, and recycling. Several
      adaptors, motor, and scaffold proteins contribute to the regulation of CFTR
      stability and are involved in continuously assessing its structure through
      peripheral quality control systems. Regulation of CFTR biogenesis and traffic
      (and its dysregulation by mutations, such as the most common F508del) determine
      its overall activity and thus contribute to the fine modulation of chloride
      secretion and hydration of epithelial surfaces. This review covers old and recent
      knowledge on CFTR folding and trafficking from its synthesis to the regulation of
      its stability at the plasma membrane and highlights how several of these steps
      can be modulated to promote the rescue of mutant CFTR.

PMID- 27699456
TI  - Diagnosis and management of skin and soft tissue infections in the intensive care
      unit: a review.
AB  - PURPOSE: To review the salient features of the diagnosis and management of the
      most common skin and soft tissue infections (SSTI). This review focuses on severe
      SSTIs that require care in an intensive care unit (ICU), including toxic shock
      syndrome, myonecrosis/gas gangrene, and necrotizing fasciitis. METHODS:
      Guidelines, expert opinion, and local institutional policies were reviewed.
      RESULTS: Severe SSTIs are common and their management complex due to regional
      variation in predominant pathogens and antimicrobial resistance patterns, as well
      as variations in host immune responses. Unique aspects of care for SSTIs in the
      ICU are discussed, including the role of prosthetic devices, risk factors for
      bacteremia, and the need for surgical consultation. SSTI mimetics, the role of
      dermatologic consultation, and the unique features of SSTIs in immunocompromised
      hosts are also described. CONCLUSIONS: We provide recommendations for clinicians
      regarding optimal SSTI management in the ICU setting.

PMID- 27699457
TI  - The rate of brain death and organ donation in patients resuscitated from cardiac
      arrest: a systematic review and meta-analysis.
AB  - BACKGROUND: The occurrence of brain death in patients with hypoxic-ischaemic
      brain injury after resuscitation from cardiac arrest creates opportunities for
      organ donation. However, its prevalence is currently unknown. METHODS: Systematic
      review. MEDLINE via PubMed, ISI Web of Science and the Cochrane Database of
      Systematic Reviews were searched for eligible studies (2002-2016). The prevalence
      of brain death in adult patients resuscitated from cardiac arrest and the rate of
      organ donation among brain dead patients were summarised using a random effect
      model with double-arcsine transformation. The quality of evidence (QOE) was
      evaluated according to the GRADE guidelines. RESULTS: 26 studies [16 on
      conventional cardiopulmonary resuscitation (c-CPR), 10 on extracorporeal CPR (e
      CPR)] included a total of 23,388 patients, 1830 of whom developed brain death at
      a mean time of 3.2 +/- 0.4 days after recovery of circulation. The overall
      prevalence of brain death among patients who died before hospital discharge was
      12.6 [10.2-15.2] %. Prevalence was significantly higher in e-CPR vs. c-CPR
      patients (27.9 [19.7-36.6] vs. 8.3 [6.5-10.4] %; p < 0.0001). The overall rate of
      organ donation among brain dead patients was 41.8 [20.2-51.0] % (9/26 studies,
      1264 patients; range 0-100 %). The QOE was very low for both outcomes.
      CONCLUSIONS: In patients with hypoxic-ischaemic brain injury following CPR, more
      than 10 % of deaths were due to brain death. More than 40 % of brain-dead
      patients could donate organs. Patients who are unconscious after resuscitation
      from cardiac arrest, especially when resuscitated using e-CPR, should be
      carefully screened for signs of brain death.

PMID- 27699458
TI  - Long-term outcome of anterior cruciate ligament tear without reconstruction: a
      longitudinal prospective study.
AB  - PURPOSE: To analyse subjective and objective long-term outcomes of patients with
      anterior cruciate ligament (ACL)-deficient knees and limited demands regarding
      sportive activities. This subgroup of patients might be well-treated without
      ligament reconstruction. METHODS: We included 303 patients with unilateral tears
      of the ACL and conservative treatment into a prospective study. Mean age at
      injury was 33.8 (min. 18, max. 66) years. Follow-up was 27.1 (min. 21.3, max.
      31.5) years. Follow-up examinations were conducted 12 and 27 years after injury.
      At the last follow-up we analysed 50 patients completely. To evaluate clinical
      and radiological outcomes we used the Lysholm score, Tegner activity scale,
      visual analogue scale for pain (VAS-pain), KOOS and Sherman score. RESULTS:
      Subjective outcome (Lysholm score and VAS-pain scale) improved between the 12th
      and 27th year after anterior cruciate ligament tear. At the same time activity
      level (Tegner activity scale) decreased. Also, arthritis (Sherman score) worsened
      over time. Twenty-seven years after injury, 90 % of the patients rated their ACL
      deficient knee as normal or almost normal; 10 % of the patients rated it as
      abnormal. The findings of this study show that there is a subgroup of patients
      with ACL tears who are well treated with physiotherapy alone, not reconstructing
      the ligament. Also, other authors found this correlation between activity level
      reduction and better subjective outcome. CONCLUSIONS: Conservative treatment of
      an ACL tear is a good treatment option for patients with limited demands
      regarding activity. Patient age, sportive activities and foremost subjective
      instability symptoms in daily life should be considered when deciding for or
      against ACL reconstruction.

PMID- 27699459
TI  - Description and reproducibility assessment of a new computerised tomography scan
      index to measure the glenoid orientation in relation to the anterior glenoid
      surface.
AB  - PURPOSE: To propose and to assess the reproducibility of a new method (GO
      [glenoid orientation] index) for the estimation of the glenoid orientation in
      relation to the anterior surface of the glenoid. METHODS: This is a retrospective
      study on computed tomography (CT) scan. The GO index was defined as the angle
      formed by a line perpendicular to the tangent to the anterior surface of the
      scapula and the glenoid line (which is defined as the line connecting the
      anterior and the posterior rim of the glenoid). The measurements were performed
      at the level of the glenoid where its diameter is the greatest. Two independent
      observers performed each measurement twice. The intra- and inter-observer
      reproducibility was evaluated by the Pearson coefficient (r) and the intra-class
      correlation coefficient (rho, ICC). The correlation between GO index and glenoid
      version as described by Friedman was also studied. RESULTS: Seventy-eight CT
      scans were analysed, 38 shoulders with glenohumeral arthritis and 40 healthy
      shoulders, 32 females/46 males, mean age 53.9 +/- 22.7 years. The measures were
      all highly correlated (r > 0.50, p = 0.00001). The intra- and inter-observer
      reproducibility was good to excellent (0.71 < rho < 0.84, p = 0.00001). GO index
      was 26.9 +/- 6.3 degrees , 28.4 +/- 6 degrees  in the group with glenohumeral
      osteoarthritis and 25.5 +/- 6.4 degrees  in the healthy group, p = 0.04. The
      glenoid version was -0.8 +/- 7.9 degrees  in the group with glenohumeral
      osteoarthritis and -3.9 +/- 6 degrees  in the healthy group, p = 0.05. No
      agreement was found between the glenoid version and GO index. CONCLUSIONS: GO
      index is simple and reproducible. It could be very useful for the pre-operative
      planning and intra-operative positioning of the implants in total shoulder
      arthroplasty.

PMID- 27699460
TI  - Anomalous branching pattern of the portal vein: right posterior portal vein
      originating from the left portal vein.
AB  - PURPOSE: To introduce a rare variant branching pattern of the portal vein with
      clinical relevance. METHODS: A 55-year-old man was examined by contrast-enhanced
      computed tomography to investigate the cause of fever and mildly elevated hepatic
      enzyme levels. RESULTS: Based on computed tomography, liver abscesses were
      identified which may have caused the fever and elevated hepatic enzyme levels.
      And a variation in the branching pattern of the portal vein was also detected in
      this patient, which has not been reported previously; the right posterior portal
      vein originated from the end of the horizontal part of the left portal vein.
      Identification of this rare branching pattern of the portal vein prior to
      hepatectomy, liver transplantation, and portal vein embolization is considered
      important to prevent complications. CONCLUSIONS: A rare variant in which the
      right posterior portal vein originated from the left portal vein was identified.
      Recognition of this variant may be important prior to surgical or interventional
      radiological strategies.

PMID- 27699462
TI  - Barbed Sutures in Body-Contouring: Outcome Analysis of 695 Procedures in 623
      Patients and Technical Advances.
AB  - INTRODUCTION: Surgical wound closure is often complicated by suture-related
      issues. The recent introduction of knotless barbed sutures may address the
      shortcomings of conventional sutures and offer the additional benefit of reduced
      operating time. In this paper, we describe our experience with barbed sutures for
      body-contouring procedures. We share technical insights and evaluate
      postoperative complications. PATIENTS AND METHODS: A retrospective assessment of
      prospectively collected data over a period of more than 5 years was undertaken.
      Six hundred twenty-three consecutive patients underwent 695 body-contouring
      procedures with barbed suture closure. Patients were followed for at least 12
      weeks postoperatively. Patient demographics, operation time as well as suture
      related complications, such as wound dehiscence and wound site infection were
      recorded and analyzed. RESULTS: Barbed sutures can facilitate skin closure,
      rectus plication, quilting, and deep layer closure in body-contouring procedures.
      The average operating time in our study cohort was 108 min with reduction
      mammoplasty being the quickest (94 min) and bodylift (156 min) being the slowest
      procedure. Sixty-eight patients experienced suture-related complications
      resulting in an overall complication rate of 9.7 % with thigh lift having the
      most (15 %) and reduction mammoplasty (7 %) the fewest adverse events.
      CONCLUSION: The use of barbed sutures allows quick closure of lengthy body
      contouring incision lines with low complication rates. Our observations support
      that barbed sutures are safe, convenient and effective. In our hands barbed
      sutures appear to be superior to traditional wound-closure techniques in body
      contouring procedures. 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- 27699461
TI  - The Use of Integra Dermal Regeneration Template Versus Flaps for Reconstruction
      of Full-Thickness Scalp Defects Involving the Calvaria: A Cost-Benefit Analysis.
AB  - BACKGROUND: INTEGRA(r) Dermal Regeneration Template is a well-known and widely
      used acellular dermal matrix. Although it helps to solve many challenging
      problems in reconstructive surgery, the product cost may make it an expensive
      alternative compared to other reconstruction procedures. This retrospective study
      aims at comparing INTEGRA-based treatment to flap surgery in terms of cost and
      benefit. PATIENTS AND METHODS: We considered only patients treated for scalp
      defects with bone exposure in order to obtain two groups as homogeneous as
      possible. We identified two groups of patients: 17 patients treated with INTEGRA
      and 18 patients treated with flaps. All patients were admitted in our institution
      between 2004 and 2010, and presented a defect of the scalp following trauma or
      surgery for cancer, causing a loss of the soft tissues of the scalp with bone
      exposure without pericranium. To calculate the cost in constant euros of each
      treatment, three parameters were evaluated for each patient: cost of the surgical
      procedure (number of doctors and nurses involved, surgery duration, anesthesia,
      material used for surgery), hospitalization cost (hospitalization duration,
      dressings, drugs, topical agents), and outpatient cost (number of dressing
      changes, personnel cost, dressings type, anti-infective agents). The statistical
      test used in this study was the Wilcoxon Mann-Whitney (alpha = 0.05). RESULTS: No
      significant difference was characterized between the two groups for gender, age,
      presence of diabetes, mean defect size, and number of surgical procedures. All
      patients healed with good quality and durable closure. The median total cost per
      patient was ?11,121 (interquartile range (IQR) 8327-15,571) for the INTEGRA group
      and ?7259 (IQR 1852-24,443) for the flap group (p = 0.34). A subgroup of patients
      (six patients in the INTEGRA group and five patients in the flap group) showing
      defects larger than 100 cm2 were considered in a second analysis. Median total
      cost was ?11,825 (IQR 10,695-15,751) for the INTEGRA group and ?23,244 (IQR
      17,348-26,942) for the flap group. CONCLUSION: Both treatments led to a good
      healing of the lesions with formation of soft and resistant tissue. No
      significant difference was characterized between the two groups for days of
      hospitalization and costs. In cases of patients with defects larger than 100 cm2
      for whom major surgery is needed, the treatment with INTEGRA seemed to be less
      expensive than the treatment with free flaps or pedicle flaps. 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 A5 online Instructions to Authors.
      www.springer.com/00266 .

PMID- 27699463
TI  - A Potential Complication of Barbed Sutures Preventing Foreign Body Granulomas
      Induced by Surgical Cloth Particles.

PMID- 27699464
TI  - Evaluation of LD decay and various LD-decay estimators in simulated and SNP-array
      data of tetraploid potato.
AB  - KEY MESSAGE: The number of SNPs required for QTL discovery is justified by the
      distance at which linkage disequilibrium has decayed. Simulations and real potato
      SNP data showed how to estimate and interpret LD decay. The magnitude of linkage
      disequilibrium (LD) and its decay with genetic distance determine the resolution
      of association mapping, and are useful for assessing the desired numbers of SNPs
      on arrays. To study LD and LD decay in tetraploid potato, we simulated
      autotetraploid genotypes and used it to explore the dependence on: (1) the number
      of haplotypes in the population (the amount of genetic variation) and (2) the
      percentage of haplotype specific SNPs (hs-SNPs). Several estimators for short
      range LD were explored, such as the average r 2, median r 2, and other
      percentiles of r 2 (80, 90, and 95 %). For LD decay, we looked at LD1/2,90, the
      distance at which the short-range LD is halved when using the 90 % percentile of
      r 2 at short range, as estimator for LD. Simulations showed that the performance
      of various estimators for LD decay strongly depended on the number of haplotypes,
      although the real value of LD decay was not influenced very much by this number.
      The estimator LD1/2,90 was chosen to evaluate LD decay in 537 tetraploid
      varieties. LD1/2,90 values were 1.5 Mb for varieties released before 1945 and 0.6
      Mb in varieties released after 2005. LD1/2,90 values within three different
      subpopulations ranged from 0.7 to 0.9 Mb. LD1/2,90 was 2.5 Mb for introgressed
      regions, indicating large haplotype blocks. In pericentromeric heterochromatin,
      LD decay was negligible. This study demonstrates that several related factors
      influencing LD decay could be disentangled, that no universal approach can be
      suggested, and that the estimation of LD decay has to be performed with great
      care and knowledge of the sampled material.

PMID- 27699465
TI  - Vascular comorbidities in multiple sclerosis: a nationwide study from Denmark.
AB  - To investigate the occurrence of vascular comorbidities before and after the
      clinical onset of multiple sclerosis. In this combined case-control and cohort
      study, all Danish born citizens with onset of multiple sclerosis 1980-2005 were
      identified from the Danish Multiple Sclerosis Registry and randomly matched with
      controls regarding year of birth, gender, and municipality on January 1st in the
      year of multiple sclerosis (MS) onset (index date). Individual-level information
      on comorbidities was obtained from several independent nationwide registries and
      linked to the study population by unique personal identification numbers. To
      assess the presence of vascular comorbidities before and after MS onset, cases
      and controls were followed from January 1977 to the index date, and from the
      index date through December 2012. We used logistic regression to calculate odds
      ratios (ORs) and Cox regression to calculate hazard ratios (HRs). Before the
      index date, MS cases had a decreased probability for cerebrovascular comorbidity
      [OR 0.69 (95 % CI 0.48-0.99, p = 0.043)], and a numerically but not statistically
      significant decreased probability for cardiovascular comorbidity [OR 0.87 (95 %
      CI 0.71-1.07, p = 0.188)]. After the index date, MS cases had an increased risk
      for cerebrovascular comorbidity [HR 1.84 (95 % CI 1.69-2.00, p < 0.0005)], and
      for cardiovascular comorbidity [HR 1.08 (95 % CI 1.02-1.15, p = 0.013)]. The
      lower occurrence of cerebrovascular comorbidities in cases prior to MS onset
      could be due to protective immune mechanisms, while the higher occurrence of
      vascular comorbidities in cases after MS onset could be because of converging
      causal pathways of the coexisting diseases. These findings deserve to be studied
      closer in a broader spectrum of comorbidities in MS.

PMID- 27699466
TI  - An early case of a natural barrier to axonal degeneration.

PMID- 27699467
TI  - Isaacs' syndrome with overlapping myopathy as the first manifestation of AL
      amyloidosis.

PMID- 27699469
TI  - Retraction Note to: The exocyst in Candida albicans polarized secretion and
      filamentation.

PMID- 27699468
TI  - Concomitant low back pain impairs outcomes after primary total knee arthroplasty
      in patients over 65 years: a prospective, matched cohort study.
AB  - INTRODUCTION: Knee osteoarthritis and low back pain (LBP) are two conditions with
      relatively high prevalence in patients over 65 years. The objective was to
      determine the effect of symptomatic LBP on the patient-reported outcome after
      primary TKA. MATERIAL AND METHOD: A cohort of 48 patients with concomitant LBP
      was prospectively matched 1:2 with patients without LBP for gender, age, body
      mass index and preoperative knee function. LBP severity was measured with the
      Oswestry Disability Index (ODI). Patient-reported outcomes were assessed with
      reduced Short-Form (SF12), Western Ontario and McMaster Universities score
      (WOMAC), and visual analogue scale (VAS) for satisfaction. Functional outcome was
      assessed with the Knee Society Scores (KSS). RESULTS: The mean postoperative
      follow-up was 3.2 years. At last follow-up, LBP cohort had significantly worse
      SF12, WOMAC, KSS and VAS scores than those patients without LBP. Preoperative ODI
      score was significantly correlated with outcomes. CONCLUSION: Worse functional
      and patient-reported outcomes were obtained in patients over 65 years with
      concomitant LBP, and this was related to the intensity of preoperative LBP.
      Despite successful outcome in the knee, the LBP usually remains after TKA and
      this may impair satisfaction and patient-reported outcomes. These patients should
      be properly informed about their potential outcomes.

PMID- 27699471
TI  - Histopathological evaluation and long-term results of soft tissue preservation
      technique in cholesteatoma surgery.
AB  - The goal of cholesteatoma surgery is total removal of the cholesteatoma matrix
      and prevention of recurrence. Preservation of soft tissue in the attic is
      reported to improve post-operative middle ear aeration, and thus prevents
      recurrence. However, the histology and nature of the preserved tissue have rarely
      been reported. The aim of this study is to clarify the histology of the preserved
      soft tissue in cholesteatoma surgery, and to show its relationship to the
      clinical course. Surgical specimens were obtained from ten patients with pars
      flaccida-type cholesteatoma. In these patients, cholesteatoma occupied the attic
      and the mastoid cavity. The cholesteatoma was removed so as not to expose the
      bone in the attic. After the removal of the lesions, soft tissue was harvested
      from the floor of the attic, using cupped forceps. The specimens were fixed with
      10 % formalin, and stained with hematoxylin-eosin. The patients were followed-up
      for 8 years after the surgery. No patients showed post-operative inner ear
      disturbance or facial nerve palsy. In one patient, residual lesion was found
      during the revision surgery. The area of residual lesion was not explored during
      the first operation. Two other patients showed recurrent cholesteatoma in the
      pars tensa; one of these patients had accompanying otorrhea. The other seven
      patients showed no residual or recurrent cholesteatoma 8 years after the surgery.
      The histological examination showed that the harvested tissue was mainly composed
      of collagen fiber and fibroblasts. Ciliary epithelial cells were found in one
      patient. In three patients, cysts of mucosal remnants (glandular cysts), were
      embedded in the connective tissue. Two of these three patients experienced
      recurrent cholesteatoma, while the other seven patients were without recurrence
      at follow-up. Preservation of soft tissue behind the cholesteatoma matrix is a
      safe technique if the surgical field is fully visible. In most cases, the
      preserved tissue was fibrous connective tissue and lacked the characteristics of
      mucosa. The glandular cysts in the preserved soft tissue seem to be related to
      the recurrence of cholesteatoma.

PMID- 27699472
TI  - Cavernous hemangioma: a term to be canceled.

PMID- 27699470
TI  - Ethanolgel sclerotherapy of venous malformations improves health-related quality
      of-life in adults and children - results of a prospective study.
AB  - OBJECTIVES: To assess the treatment-induced changes of health-related quality-of
      life (HRQoL) in patients with venous malformations (VM) who underwent ethanol gel
      sclerotherapy. METHODS: The prospective study in children and adults was approved
      by the local ethics committee. 31 patients (mean age 23.42 years, range 6.6 -
      46.5; 26 female, 5 male) with VM were included. Patients' self-assessed HRQoL was
      measured before and after treatment using psychometrically validated
      questionnaires for adults and children. Differences were analysed with a paired t
      test. RESULTS: 58 sclerotherapy sessions were performed. The Physical Component
      Summary (PCS) at baseline was 43.69 and increased significantly (p = 0.01122) to
      48.95 after treatment. The bodily pain (BP) scale increased significantly from
      37.94 to 48.56 (p = 0.00002), the general health (GH) scale increased
      significantly from 46.69 to 52.17 (p = 0.00609). Baseline Physical Summary Score
      (PHS) in children increased significantly after treatment (p < 0.00001) from
      25.25 to 45.89. The baseline Psychosocial Summary Score (PSS) in children was
      51.08 and increased significantly (p = 0.00031) after treatment to 58.84.
      CONCLUSION: Paediatric and adult patients with VM suffer from bodily pain with
      overall reduced physical functioning. After sclerotherapy, these restrictions are
      successfully returning to normal levels with a positive effect on mental and
      psychosocial domains. KEY POINTS: * Sclerotherapy in venous malformation patients
      has an unknown effect on health-related quality-of-life * Prospective study
      showed improvements in bodily pain and general health in adults * Children and
      adults improved from treatment with ethanol gel * Sclerotherapy is an appropriate
      therapy.

PMID- 27699473
TI  - Efficient targeted multiallelic mutagenesis in tetraploid potato (Solanum
      tuberosum) by transient CRISPR-Cas9 expression in protoplasts.
AB  - KEY MESSAGE: Altered starch quality with full knockout of GBSS gene function in
      potato was achieved using CRISPR-Cas9 technology, through transient transfection
      and regeneration from isolated protoplasts. Site-directed mutagenesis (SDM) has
      shown great progress in introducing precisely targeted mutations. Engineered
      CRISPR-Cas9 has received increased focus compared to other SDM techniques, since
      the method is easily adapted to different targets. Here, we demonstrate that
      transient application of CRISPR-Cas9-mediated genome editing in protoplasts of
      tetraploid potato (Solanum tuberosum) yielded mutations in all four alleles in a
      single transfection, in up to 2 % of regenerated lines. Three different regions
      of the gene encoding granule-bound starch synthase (GBSS) were targeted under
      different experimental setups, resulting in mutations in at least one allele in 2
      12 % of regenerated shoots, with multiple alleles mutated in up to 67 % of
      confirmed mutated lines. Most mutations resulted in small indels of 1-10 bp, but
      also vector DNA inserts of 34-236 bp were found in 10 % of analysed lines. No
      mutations were found in an allele diverging one bp from a used guide sequence,
      verifying similar results found in other plants that high homology between guide
      sequence and target region near the protospacer adjacent motif (PAM) site is
      essential. To meet the challenge of screening large numbers of lines, a PCR-based
      high-resolution fragment analysis method (HRFA) was used, enabling identification
      of multiple mutated alleles with a resolution limit of 1 bp. Full knockout of
      GBSS enzyme activity was confirmed in four-allele mutated lines by phenotypic
      studies of starch. One remaining wild-type (WT) allele was shown sufficient to
      maintain enough GBSS enzyme activity to produce significant amounts of amylose.

PMID- 27699474
TI  - Atlas of human diseases influenced by genetic variants with extreme allele
      frequency differences.
AB  - Genetic variants with extreme allele frequency differences (EAFD) may underlie
      some human health disparities across populations. To identify EAFD loci, we
      systematically analyzed and characterized 81 million genomic variants from 2504
      unrelated individuals of 26 world populations (phase III of the 1000 Genomes
      Project). Our analyses revealed a total of 434 genes, 15 pathways, and 18
      diseases and traits influenced by EAFD variants from five continental
      populations. They included known EAFD genes, such as LCT (lactose tolerance),
      SLC24A5 (skin pigmentation), and EDAR (hair morphology). We found many novel EAFD
      genes, including TBC1D2B (autophagy mediator), TRIM40 (gastrointestinal
      inflammatory regulator), KRT71, KRT75, KRT83, and KRTAP10-1 (hair and epithelial
      keratin synthesis), PIK3R3 (insulin receptor interaction), DARS (neurological
      disorders), and NACA2 (skin inflammatory response). Our results also showed four
      complex diseases significantly associated with EAFD loci, including asthma
      (adjusted enrichment P = 4 * 10-8), type I diabetes (P = 6 * 10-9), alcohol
      consumption (P = 0.0002), and attention deficit/hyperactivity disorder (P =
      0.003). This study provides a comprehensive atlas of genes, pathways, and human
      diseases significantly influenced by EAFD variants.

PMID- 27699477
TI  - Comprehensive analysis of the cellulolytic system reveals its potential for
      deconstruction of lignocellulosic biomass in a novel Streptomyces sp.
AB  - The giant snail Achatina fulica is considered an invasive species in most
      territories in which it was introduced, due to its ability to process a large
      amount of lignocellulose as a consequence of the presence of a cellulolytic
      associated microflora. Streptomyces are well known as crucial agents in the
      decomposition of complex polymers in soil environments and also as cellulolytic
      symbionts commonly associated with herbivore insects. Here, we employed a
      combination of genomic and biochemical tools for a detailed evaluation of the
      cellulolytic potential of Streptomyces sp. I1.2, an aerobic bacterium isolated
      from the intestinal lumen of A. fulica in a screening for cellulolytic bacteria.
      Genomic analysis revealed that the ratio and diversity of CAZy domains and GH
      families coded by Streptomyces sp. I1.2 are comparable to those present in other
      highly cellulolytic bacteria. After growth on crystalline cellulose or sugarcane
      bagasse as sole carbon sources, the functionality of several genes encoding
      endoglucanases, cellobiohydrolases, xylanases, CBMs, and one beta-glucosidase
      were confirmed by the combination of enzymatic activity measurements, zymography,
      TLC, and cellulose-binding assays. The endoglucanases secreted by this isolate
      were stable at 50  degrees C and exhibited activity over a broad pH range between
      4.0 and 8.0. The endoglucanases and cellobiohydrolases secreted by Streptomyces
      sp. I1.2 exhibited specific activities that were similar to the levels present in
      a commercial cellulase preparation from Trichoderma reesei, while I1.2 xylanase
      levels were even 350 % higher. The results presented here show that Streptomyces
      sp. I1.2 is promising for future biotechnological applications, since it is able
      to produce endoglucanases, cellobiohydrolases, and xylanases in appreciable
      amounts when grown on a low-cost residue such as sugarcane bagasse.

PMID- 27699478
TI  - Cone beam computed tomography and its image guidance technology during
      percutaneous nucleoplasty procedures at L5/S1 lumbar level.
AB  - OBJECTIVE: To demonstrate the feasibility of percutaneous nucleoplasty procedures
      at L5/S1 level using cone beam CT (CBCT) and its associated image guidance
      technology for the treatment of lumbar disc herniation (LDH). MATERIALS AND
      METHODS: We retrospectively reviewed 25 cases (20 men, 5 women) of LDH at L5/S1
      levels. CBCT as guidance imaging was chosen after a first unsuccessful
      fluoroscopy attempt that was related to complex anatomy (n = 15), rapid
      pathological changes due to degenerative diseases (n = 7) or both (n = 3).
      Technical success, defined as correct needle positioning in the target LDH, and
      safety were evaluated; overall procedure time and radiation dose were registered.
      A visual analog scale (VAS) was used to evaluate pain and discomfort pre
      intervention after 1 week and 1, 3, and 6 months after the procedure. RESULTS:
      Technical success was 100 %; using CBCT as guidance imaging the needle was
      correctly positioned at the first attempt in 20 out of 25 patients. Neither major
      nor minor complications were registered during or after the procedure. The
      average procedure time was 11 min and 56 s (range, 9-15 min), whereas mean
      procedural radiation dose was 46.25 Gy.cm2 (range 38.10-52.84 Gy.cm2), and mean
      fluoroscopy time was 5 min 34 s (range 3 min 40 s to 6 min 55 s). The VAS pain
      score decreased significantly from 7.6 preoperatively to 3.9 at 1 week, 2.8 at 1
      month, 2.1 at 3 months, and 1.6 at 6 months postoperatively. CONCLUSIONS: CBCT
      guided percutaneous nucleoplasty is a highly effective technique for LDH with
      acceptable procedure time and radiation dose.

PMID- 27699476
TI  - The Association Between Bone Mineral Density and Airflow Limitation in a Cohort
      of Fit Elderly Women.
AB  - PURPOSE: As studies examining the association between bone mineral density (BMD)
      and airflow limitation (AL) have produced conflicting results, the current one
      set out to analyze if and to what degree there are any correlations between these
      variables in a population of fit elderly women. METHODS: One hundred and twenty
      one non-smoking, fit and healthy women (age >= 65 years) underwent anthropometric
      assessment, laboratory testing (serum 25-hydroxy vitamin D, parathormone, and
      cytokine levels), pulmonary function testing (PFT), and dual-energy X-ray
      absorptiometry to evaluate BMD values of the lumbar and femoral regions. RESULTS:
      A significant positive association was found between FEV1/FVC ratio (Tiffeneau
      index), a sensitive index of AL, and lumbar and femoral BMD; a 10 % increase in
      the FEV1/FVC ratio resulted in a significant increase of 0.025 g/cm2 in the total
      hip (p = 0.05), 0.027 g/cm2 in the femoral neck (p = 0.02), 0.028 g/cm2 in the
      femoral trochanter (p = 0.01), and 0.047 g/cm2 in the lumbar (p = 0.03) BMDs.
      Binary logistic analyses demonstrated more than a threefold higher risk of low
      BMD values for the lowest FEV1/FVC quartile in the lumbar (OR 4.62, 95 % CI 1.48
      14.40, p = 0.008), total hip (OR 4.09, 95 % CI 1.28-13.05, p = 0.02 for the
      second quartile), and femoral trochanter regions (OR 3.90, 95 % CI 1.25-12.20, p
      = 0.02 for the third quartile). CONCLUSIONS: AL was associated with a higher risk
      of reduced BMD in healthy, fit elderly women.

PMID- 27699479
TI  - Intra-articular pathology associated with isolated posterior cruciate ligament
      injury on MRI.
AB  - OBJECTIVE: Unlike with anterior cruciate ligament injury, little is known about
      the prevalence of intra-articular pathology associated with isolated posterior
      cruciate ligament (PCL) injury in the knee. The objectives of this study were to
      characterize and identify the frequency of meniscal tears and osteochondral
      injuries in these patients, and to see if management might be affected. MATERIALS
      AND METHODS: Altogether, 48 knee MRI exams with isolated PCL tears were evaluated
      for the presence of: grade and location of PCL tear, meniscal tear, articular
      chondral lesion, bone bruise, and fracture. Comparisons between PCL tear grade
      and location, as well as mechanism of injury when known, with the presence of
      various intra-articular pathologies, were made using the chi-square or Fisher's
      exact test as appropriate. RESULTS: In all, 69 % of isolated PCL tears occur in
      the midsubstance, 27 % proximally. Meniscal tears were seen in 25 % of knees,
      involving all segments of both menisci, except for the anterior horn medial
      meniscus. Altogether, 23 % had focal cartilage lesions, usually affecting the
      central third medial femoral condyle and medial trochlea, while 12.5 % of knees
      had fractures, and 48 % demonstrated bone bruises, usually involving the central
      to anterior tibiofemoral joint. The presence of a fracture (p = 0.0123) and
      proximal location of PCL tear (p = 0.0016) were both associated with the
      hyperextension mechanism of injury. There were no statistically significant
      associations between PCL tear grade and presence of intra-articular abnormality.
      CONCLUSION: Potentially treatable meniscal tears and osteochondral injuries are
      relatively prevalent, and demonstrable on MRI in patients with isolated acute PCL
      injury of the knee.

PMID- 27699475
TI  - Tooth agenesis and orofacial clefting: genetic brothers in arms?
AB  - Tooth agenesis and orofacial clefts represent the most common developmental
      anomalies and their co-occurrence is often reported in patients as well in animal
      models. The aim of the present systematic review is to thoroughly investigate the
      current literature (PubMed, EMBASE) to identify the genes and genomic loci
      contributing to syndromic or non-syndromic co-occurrence of tooth agenesis and
      orofacial clefts, to gain insight into the molecular mechanisms underlying their
      dual involvement in the development of teeth and facial primordia. Altogether, 84
      articles including phenotype and genotype description provided 9 genomic loci and
      26 gene candidates underlying the co-occurrence of the two congenital defects:
      MSX1, PAX9, IRF6, TP63, KMT2D, KDM6A, SATB2, TBX22, TGFalpha, TGFbeta3,
      TGFbetaR1, TGFbetaR2, FGF8, FGFR1, KISS1R, WNT3, WNT5A, CDH1, CHD7, AXIN2,
      TWIST1, BCOR, OFD1, PTCH1, PITX2, and PVRL1. The molecular pathways, cellular
      functions, tissue-specific expression and disease association were investigated
      using publicly accessible databases (EntrezGene, UniProt, OMIM). The Gene
      Ontology terms of the biological processes mediated by the candidate genes were
      used to cluster them using the GOTermMapper (Lewis-Sigler Institute, Princeton
      University), speculating on six super-clusters: (a) anatomical development, (b)
      cell division, growth and motility, (c) cell metabolism and catabolism, (d) cell
      transport, (e) cell structure organization and (f) organ/system-specific
      processes. This review aims to increase the knowledge on the mechanisms
      underlying the co-occurrence of tooth agenesis and orofacial clefts, to pave the
      way for improving targeted (prenatal) molecular diagnosis and finally to reflect
      on therapeutic or ultimately preventive strategies for these disabling conditions
      in the future.

PMID- 27699481
TI  - A kinetic model for flavonoid production in tea cell culture.
AB  - As one of the strategies for efficient production of a metabolite from cell
      cultures, a kinetic model is very useful tool to predict productivity under
      various culture conditions. In this study, we propose a kinetic model for
      flavonoid production in tea cell culture based on the cell life cycle and
      expression of PAL, the gene encoding phenylalanine ammonia-lyase (PAL)-the key
      enzyme in flavonoid biosynthesis. The flavonoid production rate was considered to
      be related to the amount of active PAL. Synthesis of PAL was modelled based on a
      general gene expression/translation mechanism, including the transcription of DNA
      encoding PAL into mRNA and the translation of PAL mRNA into the PAL protein. The
      transcription of DNA was assumed to be promoted at high light intensity and
      suppressed by a feedback regulatory mechanism at high flavonoid concentrations.
      In the model, mRNA and PAL were considered to self-decompose and to be lost by
      cell rupture. The model constants were estimated by fitting the experimental
      results obtained from tea cell cultures under various light intensities. The
      model accurately described the kinetic behaviors of dry and fresh cell
      concentrations, glucose concentration, cell viability, PAL specific activity, and
      flavonoid content under a wide range of light intensities. The model simulated
      flavonoid productivity per medium under various culture conditions. Therefore,
      this model will be useful to predict optimum culture conditions for maximum
      flavonoid productivity in cultured tea cells.

PMID- 27699480
TI  - Regional cerebellar volumetric correlates of manual motor and cognitive function.
AB  - Cerebellar volume declines with aging. Few studies have investigated age
      differences in regional cerebellar volume (RCV) and their association with motor
      and cognitive function. In 213 healthy older adults, we investigated the
      association of age with motor skills, cognition and RCV. Subsequently, we studied
      the association of RCV with motor skills and cognition. RCVs were derived from T1
      weighted MRI scans using the automated SUIT segmentation method and clustered
      using principal component analysis (PCA). Motor skill (manual dexterity, tapping
      speed, bimanual visuomotor coordination, grip force) and cognition (mental
      rotation, verbal memory, inhibition, mental flexibility) were assessed.
      Behavioral measures were clustered into compounds using PCA: left hand motor
      skill, right hand motor skill, verbal memory and mental flexibility, and mental
      rotation & inhibition. Volume of the rostral middle frontal gyri (rMFG) and
      premotor areas (PMA) were related to performance for reference. Analyses were
      adjusted for age, sex, and education. Volume of the cerebellar anterior lobe and
      top of the superior posterior lobe were positively associated with motor skill.
      Volume of the bottom part of the posterior superior lobe and the inferior
      posterior lobe was positively associated with cognition. PMA volume was
      associated with cognition and motor skill and rMFG volume with motor skill.
      Although these results did not survive FDR correction, their effect sizes suggest
      that regional cerebellar volume selectively contributes to cognitive and motor
      skill. Effect sizes of cerebellar associations with performance were similar to
      those of rMFG/PMA and performance suggesting parallel contributions to
      performance.

PMID- 27699482
TI  - Anatomical influences on internally coupled ears in reptiles.
AB  - Many reptiles, and other vertebrates, have internally coupled ears in which a
      patent anatomical connection allows pressure waves generated by the displacement
      of one tympanic membrane to propagate (internally) through the head and,
      ultimately, influence the displacement of the contralateral tympanic membrane.
      The pattern of tympanic displacement caused by this internal coupling can give
      rise to novel sensory cues. The auditory mechanics of reptiles exhibit more
      anatomical variation than in any other vertebrate group. This variation includes
      structural features such as diverticula and septa, as well as coverings of the
      tympanic membrane. Many of these anatomical features would likely influence the
      functional significance of the internal coupling between the tympanic membranes.
      Several of the anatomical components of the reptilian internally coupled ear are
      under active motor control, suggesting that in some reptiles the auditory system
      may be more dynamic than previously recognized.

PMID- 27699483
TI  - ICE on the road to auditory sensitivity reduction and sound localization in the
      frog.
AB  - Frogs and toads are capable of producing calls at potentially damaging levels
      that exceed 110 dB SPL at 50 cm. Most frog species have internally coupled ears
      (ICE) in which the tympanic membranes (TyMs) communicate directly via the large,
      permanently open Eustachian tubes, resulting in an inherently directional
      asymmetrical pressure-difference receiver. One active mechanism for auditory
      sensitivity reduction involves the pressure increase during vocalization that
      distends the TyM, reducing its low-frequency airborne sound sensitivity.
      Moreover, if sounds generated by the vocal folds arrive at both surfaces of the
      TyM with nearly equal amplitudes and phases, the net motion of the eardrum would
      be greatly attenuated. Both of these processes appear to reduce the motion of the
      frog's TyM during vocalizations. The implications of ICE in amphibians with
      respect to sound localizations are discussed, and the particularly interesting
      case of frogs that use ultrasound for communication yet exhibit exquisitely small
      localization jump errors is brought to light.

PMID- 27699484
TI  - Running decreases knee intra-articular cytokine and cartilage oligomeric matrix
      concentrations: a pilot study.
AB  - INTRODUCTION: Regular exercise protects against degenerative joint disorders, yet
      the mechanisms that underlie these benefits are poorly understood. Chronic, low
      grade inflammation is widely implicated in the onset and progression of
      degenerative joint disease. PURPOSE: To examine the effect of running on knee
      intra-articular and circulating markers of inflammation and cartilage turnover in
      healthy men and women. METHODS: Six recreational runners completed a running (30
      min) and control (unloaded for 30 min) session in a counterbalanced order.
      Synovial fluid (SF) and serum samples were taken before and after each session.
      Cytokine concentration was measured in SF and serum using a multiplexed cytokine
      magnetic bead array. Ground reaction forces were measured during the run.
      RESULTS: There were no changes in serum or SF cytokine concentration in the
      control condition. The cytokine GM-CSF decreased from 10.7 +/- 9.8 to 6.2 +/- 5.9
      pg/ml pre- to post-run (p = 0.03). IL-15 showed a trend for decreasing
      concentration pre- (6.7 +/- 7.5 pg/ml) to post-run (4.3 +/- 2.7 pg/ml) (p =
      0.06). Changes in IL-15 concentration negatively correlated with the mean number
      of foot strikes during the run (r 2 = 0.67; p = 0.047). The control condition
      induced a decrease in serum COMP and an increase in SF COMP, while conversely the
      run induced an increase in serum COMP and a decrease in SF COMP. Changes in serum
      and SF COMP pre- to post-intervention were inversely correlated (r 2 = 0.47; p =
      0.01). CONCLUSIONS: Running appears to decrease knee intra-articular pro
      inflammatory cytokine concentration and facilitates the movement of COMP from the
      joint space to the serum.

PMID- 27699485
TI  - Passive and post-exercise cold-water immersion augments PGC-1alpha and VEGF
      expression in human skeletal muscle.
AB  - PURPOSE: We tested the hypothesis that both post-exercise and passive cold water
      immersion (CWI) increases PGC-1alpha and VEGF mRNA expression in human skeletal
      muscle. METHOD: Study 1 Nine males completed an intermittent running protocol (8
      * 3-min bouts at 90 % [Formula: see text], interspersed with 3-min active
      recovery (1.5-min at 25 % and 1.5-min at 50 % [Formula: see text]) before
      undergoing CWI (10 min at 8  degrees C) or seated rest (CONT) in a
      counterbalanced, randomised manner. Study 2 Ten males underwent an identical CWI
      protocol under passive conditions. RESULTS: Study 1 PGC-1alpha mRNA increased in
      CONT (~3.4-fold; P < 0.001) and CWI (~5.9-fold; P < 0.001) at 3 h post-exercise
      with a greater increase observed in CWI (P < 0.001). VEGFtotal mRNA increased
      after CWI only (~2.4-fold) compared with CONT (~1.1-fold) at 3 h post-exercise (P
      < 0.01). Study 2 Following CWI, PGC-1alpha mRNA expression was significantly
      increased ~1.3-fold (P = 0.001) and 1.4-fold (P = 0.0004) at 3 and 6 h,
      respectively. Similarly, VEGF165 mRNA was significantly increased in CWI ~1.9
      fold (P = 0.03) and 2.2-fold (P = 0.009) at 3 and 6 h post-immersion.
      CONCLUSIONS: Data confirm post-exercise CWI augments the acute exercise-induced
      expression of PGC-1alpha mRNA in human skeletal muscle compared to exercise per
      se. Additionally CWI per se mediates the activation of PGC-1alpha and VEGF mRNA
      expression in human skeletal muscle. Cold water may therefore enhance the
      adaptive response to acute exercise.

PMID- 27699486
TI  - Biofilm-associated infection: the hidden face of cerebrospinal fluid shunt
      malfunction.
AB  - Diagnosis of cerebrospinal fluid (CSF) shunt infection is difficult. Growing
      evidence links this pattern to biofilm-associated infections (BAI). Biofilm may
      explain the indolent development of the infection, and the poor efficiency of
      traditional microbiologic methods. We report the case of a patient admitted for
      hydrocephalus associated to CSF shunt malfunction. None of the clinical, serum,
      or CSF laboratory findings were in favor of an infectious process. Only scanning
      electron microscopy (SEM) revealed the presence of biofilm. Hence, despite a
      broad CSF shunt infection definition, some infections could remain undiagnosed by
      the traditional approach. This study is the first to provide some direct evidence
      for bacterial biofilm-associated CSF shunt infection.

PMID- 27699488
TI  - Late Somatic Gene 2 disrupts parental spheroids cooperatively with Volvox
      hatching enzyme A in Volvox.
AB  - MAIN CONCLUSION: We identified LSG2 as a novel lytic enzyme that accumulates in
      the parental extracellular matrix and disrupts parental spheroids cooperatively
      with VheA secreted by juveniles in Volvox. Spatiotemporally restricted
      degradation of extracellular matrix (ECM) is essential for development and
      survival in multicellular organisms. In an asexual life cycle of green algae
      Volvox, juveniles are released from parental spheroids through holes made by
      restricted degradation of parental ECM at the proper timing. Lytic enzyme(s)
      should specifically degrade parental ECM upon Volvox hatching, but little is
      known about the mechanisms of spatiotemporally restricted parental degradation.
      Here, we identified a glycoprotein encoded by the Late Somatic Gene 2 (LSG2) as a
      novel lytic enzyme that accumulates in parental ECM during the prehatching
      stages. The dual action of LSG2 and Volvox hatching enzyme A (VheA), a serine
      protease secreted by juveniles, causes the degradation of ECM sheets at all
      stages and destroys even daughter spheroids, while VheA alone disrupts spheroids
      only in the prehatching stage when LSG2 is accumulated, suggesting that the
      combination of LSG2 and VheA is sufficient to cause the degradation of ECM sheet.
      In the prehatching stage, parental spheroids became susceptible to the
      proteolysis by a mixture of bacterial proteases applied externally, which could
      be facilitated by LSG2. These results suggest that LSG2 disrupts parental ECM
      cooperatively with VheA by modifying the parental ECM to make it fragile, and
      that the appropriate activity of these enzymes is crucial for the parent-specific
      ECM degradation at the proper timing.

PMID- 27699487
TI  - Uncovering leaf rust responsive miRNAs in wheat (Triticum aestivum L.) using high
      throughput sequencing and prediction of their targets through degradome analysis.
AB  - MAIN CONCLUSION: Deep sequencing identified 497 conserved and 559 novel miRNAs in
      wheat, while degradome analysis revealed 701 targets genes. QRT-PCR demonstrated
      differential expression of miRNAs during stages of leaf rust progression. Bread
      wheat (Triticum aestivum L.) is an important cereal food crop feeding 30 % of the
      world population. Major threat to wheat production is the rust epidemics. This
      study was targeted towards identification and functional characterizations of
      micro(mi)RNAs and their target genes in wheat in response to leaf rust
      ingression. High-throughput sequencing was used for transcriptome-wide
      identification of miRNAs and their expression profiling in retort to leaf rust
      using mock and pathogen-inoculated resistant and susceptible near-isogenic wheat
      plants. A total of 1056 mature miRNAs were identified, of which 497 miRNAs were
      conserved and 559 miRNAs were novel. The pathogen-inoculated resistant plants
      manifested more miRNAs compared with the pathogen infected susceptible plants.
      The miRNA counts increased in susceptible isoline due to leaf rust, conversely,
      the counts decreased in the resistant isoline in response to pathogenesis
      illustrating precise spatial tuning of miRNAs during compatible and incompatible
      interaction. Stem-loop quantitative real-time PCR was used to profile 10 highly
      differentially expressed miRNAs obtained from high-throughput sequencing data.
      The spatio-temporal profiling validated the differential expression of miRNAs
      between the isolines as well as in retort to pathogen infection. Degradome
      analysis provided 701 predicted target genes associated with defense response,
      signal transduction, development, metabolism, and transcriptional regulation. The
      obtained results indicate that wheat isolines employ diverse arrays of miRNAs
      that modulate their target genes during compatible and incompatible interaction.
      Our findings contribute to increase knowledge on roles of microRNA in wheat-leaf
      rust interactions and could help in rust resistance breeding programs.

PMID- 27699489
TI  - Perioperative and short-term oncological outcomes of single-port surgery for
      transverse colon cancer.
AB  - PURPOSE: To compare the perioperative and short-term oncological outcomes of
      patients who underwent single-port surgery (SPS) with those of patients who
      underwent multi-port surgery (MPS) for transverse colon cancer. METHODS: The
      records of consecutive patients who underwent SPS (n = 75) or MPS (n = 41) for
      transverse colon cancer in our department between January, 2008 and December,
      2015 were analyzed retrospectively. RESULTS: Operative times were significantly
      shorter in the SPS group than in the MPS group (185 vs. 195 min, respectively; P
      = 0.043). There were no significant differences in operative procedures, blood
      loss, or extent of lymph node dissection. The rate of postoperative complications
      was similar in both groups, but the length of hospital stay was significantly
      shorter in the single-port group than in the multi-port group (8 vs. 11 days,
      respectively; P < 0.001). Oncological outcomes were similar in both groups. The
      disease-free survival rate at 2 years did not differ significantly between the
      groups (91.1 vs. 94.9 %, respectively; P = 0.414). CONCLUSIONS: Our experience
      demonstrates that SPS is safe and can provide oncological outcomes equal to those
      of MPS for transverse colon cancer.

PMID- 27699490
TI  - Simplified comorbidity score for elderly patients undergoing thoracoscopic
      surgery for lung cancer.
AB  - PURPOSE: We investigated the efficiency of the Simplified Comorbidity Score (SCS)
      for predicting postoperative complications and prognosis in elderly patients
      undergoing video-assisted thoracoscopic surgery (VATS) for lung cancer. METHODS:
      We reviewed 216 patients aged 75 years or older, who underwent pulmonary
      resection by VATS for lung cancer between January, 2005 and December, 2012. The
      SCS assigns different scores to patients' comorbidities; namely, smoking (n = 7);
      diabetes mellitus (n = 5); renal insufficiency (n = 4); and respiratory,
      neoplastic, and cardiovascular comorbidities or alcoholism (n = 1 each). Patients
      were divided into a high SCS group (SCS >= 9; n = 154) and a low SCS group (<9; n
      = 62), for a comparative analysis of differences in perioperative factors and
      prognoses. RESULTS: Limited resection was more frequent in the high SCS group (58
      %) than in the low SCS group (40 %; P = 0.02). Postoperative complications were
      more frequent in the high SCS group (45 %) than in the low SCS group (15 %; P <
      0.01). A logistic regression analysis revealed that a high SCS was significantly
      predictive of postoperative complications (odds ratio 2.7; P = 0.02). The 5-year
      overall survival rate was 79 % for the low SCS group and 52 % for the high SCS
      group (P < 0.01). CONCLUSIONS: The SCS can predict the likelihood of
      postoperative complications and prognosis of elderly patients with VATS-treated
      lung cancers.

PMID- 27699491
TI  - Involvement of cell surface TG2 in the aggregation of K562 cells triggered by
      gluten.
AB  - Gluten-induced aggregation of K562 cells represents an in vitro model reproducing
      the early steps occurring in the small bowel of celiac patients exposed to
      gliadin. Despite the clear involvement of TG2 in the activation of the antigen
      presenting cells, it is not yet clear in which compartment it occurs. Herein we
      study the calcium-dependent aggregation of these cells, using either cell
      permeable or cell-impermeable TG2 inhibitors. Gluten induces efficient
      aggregation when calcium is absent in the extracellular environment, while TG2
      inhibitors do not restore the full aggregating potential of gluten in the
      presence of calcium. These findings suggest that TG2 activity is not essential in
      the cellular aggregation mechanism. We demonstrate that gluten contacts the cells
      and provokes their aggregation through a mechanism involving the A-gliadin
      peptide 31-43. This peptide also activates the cell surface associated
      extracellular TG2 in the absence of calcium. Using a bioinformatics approach, we
      identify the possible docking sites of this peptide on the open and closed TG2
      structures. Peptide docks with the closed TG2 structure near to the GTP/GDP site,
      by establishing molecular interactions with the same amino acids involved in
      stabilization of GTP binding. We suggest that it may occur through the
      displacement of GTP, switching the TG2 structure from the closed to the active
      open conformation. Furthermore, docking analysis shows peptide binding with the
      beta-sandwich domain of the closed TG2 structure, suggesting that this region
      could be responsible for the different aggregating effects of gluten shown in the
      presence or absence of calcium. We deduce from these data a possible mechanism of
      action by which gluten makes contact with the cell surface, which could have
      possible implications in the celiac disease onset.

PMID- 27699493
TI  - Chemotherapy for advanced gastric cancer: future perspective in Japan.
AB  - Differences in clinical outcomes between advanced gastric cancer (AGC) in Asia
      and that in other regions have been discussed for a long time, although no major
      significant differences in molecular profiles have been reported. The anti-human
      epidermal growth factor receptor 2 antibody trastuzumab and the anti-vascular
      endothelial growth factor receptor 2 monoclonal antibody ramucirumab were both
      approved as a treatment for AGC on the basis of global phase 3 trials including
      Japan. In recent years, others new agents for treatment of AGC have been
      investigated in global or Asian studies. Randomized phase 2 trials in Japan
      showed a higher response rate to S-1 plus leucovorin and oxaliplatin than to
      standard S-1 plus cisplatin, which is the rationale for an ongoing phase 3 trial
      in Asia (SOLAR trial). A recent global phase 1 trial of the anti-programmed cell
      death 1 monoclonal antibody pembrolizumab showed similar efficacy results in
      Asian patients and non-Asian patients, which led to large global phase 2 and
      phase 3 studies. Although the perspective of treatment of AGC in the near future
      depends on the results of ongoing large clinical trials, individualized choice of
      treatment based on more detailed molecular information will become important.

PMID- 27699492
TI  - The safety and effectiveness profile of eldecalcitol in a prospective, post
      marketing observational study in Japanese patients with osteoporosis: interim
      report.
AB  - This large-scale post-marketing surveillance study was conducted to assess the
      safety and effectiveness of eldecalcitol treatment in patients with osteoporosis
      in a Japanese clinical setting. A total of 3567 patients with osteoporosis were
      enrolled and received eldecalcitol 0.75 MUg/day for 12 months. For this interim
      report, 3285 patients were eligible for analysis. Mean age was 74.9 +/- 8.7
      years; 86.8 % (2854/3285) were women. There were 142 reported adverse drug
      reactions (ADRs) in 129 patients (3.92 % of the total 3285 patients): the most
      common were hypercalcemia and increased blood calcium (0.88 %), renal impairment
      (0.27 %), abdominal discomfort (0.24 %), constipation (0.24 %), and pruritus
      (0.24 %). The incidence of ADRs was 5.10 % in men and 3.74 % in women. Although
      10 serious ADRs were reported in 9 patients (0.27 %), no clinically significant
      safety issues were identified. Incidence of hypercalcemia or increased blood
      calcium was 8.47 % in patients with renal impairment and only 0.74 % in patients
      without renal impairment. At last observation, the incidence of new vertebral and
      nonvertebral fractures was 2.44 % and 1.70 %, respectively. There was a
      significant increase in bone mineral density at the lumbar spine and distal
      radius. The bone turnover markers BAP, serum NTX, urinary NTX, and TRACP-5b were
      suppressed by eldecalcitol treatment in both sexes. In conclusion, consistent
      with the findings of the phase III pivotal clinical trial, eldecalcitol was shown
      to have a favorable safety profile and effectiveness in Japanese patients with
      osteoporosis. However, periodic measurements of serum calcium were required to
      prevent occurrence of hypercalcemia during eldecalcitol treatment, especially in
      patients with renal impairment.

PMID- 27699494
TI  - Survival and clinical results of a modified "crosse de hockey" procedure for
      chronic isolated patellofemoral joint osteoarthritis: mid-term follow-up.
AB  - BACKGROUND: The optimum treatment for isolated patellofemoral joint
      osteoarthritis (PFJ-OA) remains controversial. The aim of this study was to
      assess the mid-term clinical results of a modified crosse de hockey procedure for
      the treatment of isolated PFJ-OA. MATERIALS AND METHODS: We assessed 37 knees in
      31 patients treated by a modified crosse de hockey procedure. The mean age was
      57.6 years (range, 46-75 years) and mean follow-up was 90.1 months (range, 24-216
      months). We evaluated clinical and radiographic outcomes, as well as complication
      rates at the mid-term follow-up. RESULTS: The Kujala score (mean improvement of
      46.7, P < 0.001) and the Fulkerson score (mean improvement of 19, P = 0.001) were
      significantly higher compared to preoperative values. Overall clinical results
      rated excellent in 24.3 %, very good in 21.6 %, good in 35.1 %, fair in 13.5 %,
      and poor in 5.4 % of knees. Patellar tilting (P = 0.015) and congruence angle (P
      = 0.018) significantly improved postoperatively. On the other hand, the Insall
      Salvati index decreased at the time of follow-up, although it remained in the
      physiologic range. Postoperatively, consecutive disease progression in the
      tibiofemoral joint and patellofemoral joint osteoarthritis were 18.9 and 5.4 %,
      respectively. The operative complication rate was 5.4 % in this case series.
      These percentages were lower than those of alternative tibial tuberosity
      osteotomy techniques. CONCLUSION: In most patients with chronic isolated PFJ-OA,
      tibial tuberosity osteotomy by modified crosse de hockey is a reliable procedure
      that provides good/excellent mid-term clinical results. LEVEL OF EVIDENCE: Level
      IV.

PMID- 27699495
TI  - Hubble trial: time to stick to basics for treatment of haemorrhoids?
AB  - The results of the Hubble trial, a randomised controlled trial comparing
      haemorrhoidal artery ligation with rubber band ligation for early-grade
      prolapsing haemorrhoids, are discussed. The difficulties in defining treatment
      success are debated along with the trial design highlighting the pitfalls of
      previous research. A finding that haemorrhoidal artery ligation is not
      necessarily superior to cheap alternatives has implications for current practice
      and future commissioning of surgeons.

PMID- 27699496
TI  - Incidence and surgical treatment of synthetic mesh-related infectious
      complications after laparoscopic ventral rectopexy.
AB  - BACKGROUND: Prosthetic-related infection and erosion occurring after a
      laparoscopic ventral rectopexy (LVR) are rare complications, and their importance
      is often underestimated. The aim of this study was to compare the incidence rate
      and surgical management of these complications in LVR patients with polyester
      (PE) or polypropylene (PP) prostheses. METHODS: From January 2004 to June 2012,
      149 patients underwent LVR with PE and 176 underwent LVR with PP. Surgical
      management and rate of infectious and erosive prosthesis-related complications,
      depending on the type of prosthesis, were described and compared. Functional
      results after complications were assessed. RESULTS: Five patients from the PE
      prosthesis group (3.3 %), compared with two patients from the PP prosthesis group
      (1.1 %), experienced prosthesis-related infection or erosion (p = 0.16). The rate
      of erosion alone was 3.3 % in patients with a PE prosthesis, and 0.55 % in
      patients with a PP prosthesis (p = 0.06). The average time until clinical
      diagnosis of a prosthesis-related complication was identical for both groups: 31
      months (range 3-62 months). All patients underwent surgical removal of the
      prosthesis: For the five patients from the PE group, complete removal was
      performed by laparoscopy associated with a transanal procedure. For the two
      patients in the PP mesh group, laparoscopy was ineffective in removing the mesh
      which was partially removed through a subsequent transanal procedure. None of the
      patients had a protective stoma, and in all patients the complication had
      resolved 12 months after removal. Only one patient had worsening functional
      symptoms (fecal incontinence) after prosthesis removal. CONCLUSIONS: When a
      prosthesis-related infection or erosion occurs, treatment consists in the
      surgical removal of the prosthesis by laparoscopy/and/or a transanal procedure.
      Functional symptoms do not routinely recur after prosthesis removal.

PMID- 27699497
TI  - Lamivudine and fingolimod co-administration in two patients with multiple
      sclerosis and occult hepatitis B virus infection.

PMID- 27699498
TI  - Thrombolysis in dementia patients with acute stroke: is it justified?
AB  - The administration of thrombolytic therapy in elderly patients with dementia and
      acute ischemic stroke may be controversial, because the reported risk of rt-PA
      associated intracerebral hemorrhage in these patients is higher compared with
      that of patients without dementia and because these patients are already
      disabled. Moreover, there are known risk factors for hemorrhagic transformation
      in patients with dementia: amyloid angiopathy, leukoaraiosis and the presence of
      microbleeds. In this review, we describe the impact of dementia on functional
      outcome following thrombolytic therapy for acute ischemic stroke and discuss some
      of the issues related to the use of this therapy in this specific patient's
      population.

PMID- 27699499
TI  - Influence of atmospheric states in semi-arid areas on hospital admission in
      cardio-surgical department.
AB  - The influence of the changes in atmospheric state, typical for areas close to big
      deserts, on acute myocardial infarction (AMI) was analyzed. Under test was the
      group of 3256 patients (77 % males, 23 % females), hospitalized in the Cardio
      Surgical Department of Soroka Medical Center at Ben-Gurion University (BGU,
      Israel) during 2000-2008. To explore the relationship between atmospheric
      parameters and AMI, multivariate regression analysis has been performed. AMI was
      most frequent in winter to spring and least in summer. The highest number of
      cases was recorded in December and the lowest in September. Hospital admissions
      showed a higher prevalence in men than in women; the ratio is 3.3/1.0. About 60 %
      of males were aged between 45 and 65 years old with maximum ~55 (21 %), whereas
      60 % of women hospital admissions were aged between 65 and 80 years old with
      maximum ~72 (24 %). The result suggested that the monthly mean relative humidity
      at daytime and its overall daily differences, wind speed, and respirable fraction
      of particulate concentration are associated with the admission for AMI. The
      results of the study confirm the importance of atmospheric state variability for
      cardiovascular diseases.

PMID- 27699501
TI  - The glass is not yet half empty: agitation but not Varroa treatment causes
      cognitive bias in honey bees.
AB  - Honey bees (Apis mellifera) are prone to judge an ambiguous stimulus negatively
      if they had been agitated through shaking which simulates a predator attack. Such
      a cognitive bias has been suggested to reflect an internal emotional state
      analogous to humans who judge more pessimistically when they do not feel well. In
      order to test cognitive bias experimentally, an animal is conditioned to respond
      to two different stimuli, where one is punished while the other is rewarded.
      Subsequently a third, ambiguous stimulus is presented and it is measured whether
      the subject responds as if it expects a reward or a punishment. Generally, it is
      assumed that negative experiences lower future expectations, rendering the
      animals more pessimistic. Here we tested whether a most likely negatively
      experienced formic acid treatment against the parasitic mite Varroa destructor
      also affects future expectations of honey bees. We applied an olfactory learning
      paradigm (i.e., conditioned proboscis extension response) using two odorants and
      blends of these odorants as the ambiguous stimuli. Unlike agitating honey bees,
      exposure to formic acid did not significantly change the response to the
      ambiguous stimuli in comparison with untreated bees. Overall evidence suggests
      that the commonest treatment against one of the most harmful bee pests has no
      detrimental effects on cognitive bias in honey bees.

PMID- 27699500
TI  - Identification of HIF-2alpha-regulated genes that play a role in human
      microvascular endothelial sprouting during prolonged hypoxia in vitro.
AB  - During prolonged hypoxic conditions, endothelial cells change their gene
      expression to adjust to the low oxygen environment. This process is mainly
      regulated by the hypoxia-inducible factors, HIF-1alpha and HIF-2alpha. Although
      endothelial cells do not form sprouts during prolonged hypoxic culturing,
      silencing of HIF-2alpha partially restores sprout formation. The present study
      identifies novel HIF-2alpha-target genes that may regulate endothelial sprouting
      during prolonged hypoxia. The gene expression profile of primary human
      microvascular endothelial cells (hMVECs) that were cultured at 20 % oxygen was
      compared to hMVECs that were cultured at 1 % oxygen for 14 days by using genome
      wide RNA-sequencing. The differentially regulated genes in hypoxia were compared
      to the genes that were differentially regulated upon silencing of HIF-2alpha in
      hypoxia. Surprisingly, KEGG pathway analysis showed that metabolic pathways were
      enriched within genes upregulated in response to hypoxia and enriched within
      genes downregulated upon HIF-2alpha silencing. Moreover, 51 HIF-2alpha-regulated
      genes were screened for their role in endothelial sprouting in hypoxia, of which
      four genes ARRDC3, MME, PPARG and RALGPS2 directly influenced endothelial
      sprouting during prolonged hypoxic culturing. The manipulation of specific
      downstream targets of HIF-2alpha provides a new, but to be further evaluated,
      perspective for restoring reduced neovascularization in several pathological
      conditions, such as diabetic ulcers or other chronic wounds, for improvement of
      vascularization of implanted tissue-engineered scaffolds.

PMID- 27699502
TI  - Haematopoietic stem cell transplantation survivorship and quality of life: is it
      a small world after all?
AB  - PURPOSE: The aim of this qualitative study was to gain a rich understanding of
      the impact that haematopoietic stem cell transplantation (HSCT) has on long-term
      survivor's quality of life (QoL). METHOD: Participants included 441 survivors who
      had undergone HSCT for a malignant or non-malignant disease. Data were obtained
      by a questionnaire positing a single open-ended question asking respondents to
      list the three issues of greatest importance to their QoL in survivorship.
      Responses were analysed and organised into QoL themes and subthemes. RESULTS:
      Major themes identified included the following: the failing body and diminished
      physical effectiveness, the changed mind, the loss of social connectedness, the
      loss of the functional self and the patient for life. Each of these themes
      manifests different ways in which HSCT survivor's world and opportunities had
      diminished compared to the unhindered and expansive life that they enjoyed prior
      to the onset of disease and subsequent HSCT. CONCLUSIONS: HSCT has a profound and
      pervasive impact on the life of survivors-reducing their horizons and shrinking
      various parts of their worlds. While HSCT survivors can describe the ways in
      which their life has changed, many of their fears, anxieties, regrets and
      concerns are existential in nature and are ill-defined-making it exceeding
      unlikely that they would be adequately captured by standard psychometric measures
      of QoL post HSCT.

PMID- 27699503
TI  - Premedication with intravenous magnesium has a protective effect against
      cisplatin-induced nephrotoxicity.
AB  - PURPOSE: Magnesium supplementation is an effective protective method against
      cisplatin-induced nephrotoxicity (CIN); however, there are few reports regarding
      the mechanism of its nephroprotective effect. The aim of this study was to
      determine whether premedication with intravenous magnesium prevents CIN and to
      determine the relationship between its nephroprotective effect and serum
      magnesium level. METHODS: Fifty-eight patients with head and neck cancer who
      received cisplatin, docetaxel, and 5-fluorouracil (DCF) were retrospectively
      investigated. Grade 2 or more serum creatinine elevation was defined as CIN. The
      incidence of CIN was compared between a magnesium sulfate (20 mEq, 2.46 g)
      premedication group and a non-magnesium group during the first cycle and in all
      cycles. RESULTS: CIN did not occur in any patients receiving magnesium
      premedication but did occur in 5 of 29 patients during the first cycle and in 6
      patients during all subsequent cycles in patients who did not receive magnesium
      premedication. Furthermore, the variation of creatinine clearance was
      significantly worse in the non-magnesium group than in the magnesium
      premedication group from baseline. There was no difference in adverse effects or
      response rate between the two groups. Univariate analysis suggested that
      magnesium premedication significantly reduced the risk of CIN. On the other hand,
      serum magnesium depletion was seen in both groups to equal degrees despite
      supplementation. CONCLUSION: Intravenous magnesium premedication has a protective
      effect on cisplatin-induced nephrotoxicity without the influence on the serum
      magnesium level. Magnesium premedication is a simple nephroprotective method that
      does not influence other adverse effects or rate of response to chemotherapy.

PMID- 27699505
TI  - A transcriptomic resource for Douglas-fir seed development and analysis of
      transcription during late megagametophyte development.
AB  - KEY MESSAGE: Douglas-fir transcriptomics. Douglas-fir (Pseudotsuga menziesii
      (Mirb.) Franco) is economically important with extensive breeding programs and
      seed trade. However, the molecular genetics of its seed development are largely
      unknown. We developed a transcriptome resource covering key developmental stages
      of megagametophytes over time: prefertilization, fertilization, embryogenesis,
      and early, unfertilized abortion. RNA sequencing reads were assembled de novo
      into 105,505 predicted high-confidence transcripts derived from 34,521 predicted
      genes. Expression levels were estimated based on alignment of the original reads
      to the reference. Megagametophytes express a distinct set of genes compared to
      those of vegetative tissues. Transcripts related to signaling, protein turnover,
      and RNA biogenesis have lower expression values in vegetative tissues, whereas
      cell wall remodeling, solute transport, and seed storage protein transcripts have
      higher expression values in megagametophytes. Seed storage protein transcripts
      become very abundant in both pollinated and unpollinated megagametophytes over
      time, even in aborting ovules. However, the absence of protein storage bodies in
      unfertilized megagametophytes suggests extensive posttranscriptional mechanisms
      that either inhibit storage protein translation or their aggregation into protein
      bodies. This novel transcriptome resource provides a foundation for further
      important insights into conifer seed development.

PMID- 27699506
TI  - Effect of Fluid Viscosity on the Cilia-Generated Flow on a Mouse Tracheal Lumen.
AB  - Mucous flow in a tracheal lumen is generated by the beat motion of ciliated cells
      to provide a clearance function by discharging harmful dust particles and
      viruses. Due to its physiological importance, the cilia-generated flow and the
      rheological properties of mucus have been investigated intensively. The effects
      of viscosity on the cilia-generated flow, however, have not been fully clarified.
      In this study, we measured bulk background velocity of ciliary flow using a micro
      particle tracking velocimetry method under various viscosity conditions in mice.
      The results showed that the flow velocity decreased as the increase with
      viscosity of ambient fluid. Moreover, no previous study has clarified the pump
      power generated by cilia, which provides important information with regard to
      understanding the molecular motor properties of cilia. Measurements of both the
      ciliary flow and the ciliary motion were conducted to determine the cilia pump
      power. Our results indicated that the cilia pump during the effective stroke did
      not drive the ciliary flow efficiently under high viscosity conditions; these
      findings are necessary to resolve the clearance function.

PMID- 27699508
TI  - A primer on the statistical modelling of learning curves in health professions
      education.
AB  - Learning curves are a useful way of representing the rate of learning over time.
      Features include an index of baseline performance (y-intercept), the efficiency
      of learning over time (slope parameter) and the maximal theoretical performance
      achievable (upper asymptote). Each of these parameters can be statistically
      modelled on an individual and group basis with the resulting estimates being
      useful to both learners and educators for feedback and educational quality
      improvement. In this primer, we review various descriptive and modelling
      techniques appropriate to learning curves including smoothing, regression
      modelling and application of the Thurstone model. Using an example dataset we
      demonstrate each technique as it specifically applies to learning curves and
      point out limitations.

PMID- 27699509
TI  - A Public Tribute to the Editors and Publishers of Digestive Diseases and
      Sciences: Personal Experience with Authorship of 43 Publications in this Journal
      During the Last 29 Years.

PMID- 27699507
TI  - Ex Vivo Methods for Informing Computational Models of the Mitral Valve.
AB  - Computational modeling of the mitral valve (MV) has potential applications for
      determining optimal MV repair techniques and risk of recurrent mitral
      regurgitation. Two key concerns for informing these models are (1) sensitivity of
      model performance to the accuracy of the input geometry, and, (2) acquisition of
      comprehensive data sets against which the simulation can be validated across
      clinically relevant geometries. Addressing the first concern, ex vivo micro
      computed tomography (microCT) was used to image MVs at high resolution (~40
      micron voxel size). Because MVs distorted substantially during static imaging,
      glutaraldehyde fixation was used prior to microCT. After fixation, MV leaflet
      distortions were significantly smaller (p < 0.005), and detail of the chordal
      tree was appreciably greater. Addressing the second concern, a left heart
      simulator was designed to reproduce MV geometric perturbations seen in vivo in
      functional mitral regurgitation and after subsequent repair, and maintain
      compatibility with microCT. By permuting individual excised ovine MVs (n = 5)
      through each state (healthy, diseased and repaired), and imaging with microCT in
      each state, a comprehensive data set was produced. Using this data set, work is
      ongoing to construct and validate high-fidelity MV biomechanical models. These
      models will seek to link MV function across clinically relevant states.

PMID- 27699511
TI  - Genetic characterization of equine herpesvirus 1 isolates from abortion outbreaks
      in India.
AB  - Equine herpesvirus 1 (EHV1) is a common pathogen of horses that causes upper
      respiratory tract disease, abortion, neonatal death and neurological disease. The
      neurological form of disease is called equine herpesvirus myeloencephalopathy
      (EHM). During the past decade, the incidence of EHM has been on the rise in
      Europe, North America, Australia and Asia. Some EHV1 isolates causing EHM exhibit
      a single-nucleotide polymorphism (SNP) in the DNA polymerase gene (ORF30) at
      position 2254 (A2254 to G2254). Further, based on polymorphism in the ORF68, EHV1
      isolates have been classified into different groups. The aim of the present study
      was to estimate the genetic diversity of EHV1 and to determine the prevalence of
      the neuropathogenic genotype of EHV1 in India. Out of 133 clinical specimens from
      abortion cases in northern India, 56 were positive for EHV1 infection. Analysis
      of the A/G SNP by real-time PCR and sequence analysis revealed that 54 of 56
      samples (96.43 %) were of the non-neuropathogenic genotype (A2254), while two
      (3.57 %) had the neuropathogenic marker (G2254). Sequence analysis of the
      polymorphic region of ORF68 of EHV1 isolates (n = 9) from India indicated that
      the Delhi/1998, Tohana-2/2013, Hisar-2/2014 and Hisar-15/1990 isolates belonged
      to group 4, while the Jind/1996, Rajasthan/1998, Delhi-3/2007 and Tohana-5/1996
      isolates clustered within group 5. One isolate (Hisar-7/1990) exhibited SNPs at
      positions C710 and C713, forming a separate group. Here, we report for the first
      time the detection of neuropathogenic genotypes of EHV1 in India and show that
      Indian EHV1 isolates cluster within groups 4 and 5.

PMID- 27699510
TI  - Plasma Level of Interleukin-35 as an Independent Prognostic Indicator in
      Hepatocellular Carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma is a major type of liver cancer with poor
      prognosis. AIM: The aim of the study was to determine the prognostic significance
      of plasma interleukin-35 level in hepatocellular carcinoma. METHODS: A total of
      153 hepatocellular carcinoma patients and 153 healthy controls were enrolled.
      Blood samples were obtained at admission. Plasma interleukin-35 level was
      analyzed by enzyme-linked immunosorbent assay. Distribution of T cell subset and
      expression of Fas/FasL protein were detected by flow cytometry. The patients were
      followed up for 2 years. Poor prognosis was defined as death of hepatocellular
      carcinoma. RESULTS: The plasma levels of interleukin-35 were significantly higher
      in the patients than the controls (25.1 +/- 13.1, 9.3 +/- 6.3 pg/mL, P < 0.001).
      After adjusted for multiple confounding factors, the multivariate logistic
      regression analyses reported that high level of interleukin-35 (>=25.0 pg/mL) was
      associated with the poor prognosis in the patients (OR 6.63, 95 % CI 3.27-13.47).
      Compared with the patients with low level of interleukin-35 (<25.0 pg/mL), the
      patients with high level of interleukin-35 showed higher frequencies of
      CD4+CD25+FoxP3+ and CD3+Foxp3+ regulatory T cells (P < 0.001 and P < 0.001) and
      also showed higher apoptosis levels of CD8+ T cells (P < 0.001). CONCLUSION:
      Circulating interleukin-35 concentration might be an independent prognostic
      indicator in hepatocellular carcinoma. Such prognostic significance could be
      partly involved in the activation of regulatory T cell and the apoptosis of CD8+
      T cell.

PMID- 27699513
TI  - Identification of internal poly(A) tracts (IPATs) of variable lengths in a novel
      tobacco rattle virus RNA2 in potatoes.
AB  - The nucleotide (nt) sequences of two closely related isolates (CeWF-2 and CeWGH
      2) of a novel tobacco rattle virus (TRV) RNA2 were determined. The sequences of
      their RNA2-specific regions were almost identical and contained four open reading
      frames (ORFs) in an arrangement similar to that found in the previously described
      TRV TpO1 RNA2. Their predicted ORF 1 gene products shared 97 % amino acid
      sequence identity with the TpO1 coat protein, but the ORF 2 and ORF 3 gene
      products shared only 82 % sequence identity, and no appreciable sequence
      similarity was found between the CeWF-2/CeWGH-2 and TpO1 ORF 4 gene products. In
      the CeWGH-2 sequence, the RNA2-specific and RNA1-related regions were separated
      by seven adenine (A) residues. In CeWF-2, however, an internal poly(A) tract
      (IPAT) of variable size consisting of ca. 20 to 30 (A) residues was found. This
      is the first report of an IPAT occurring in a tobravirus RNA2.

PMID- 27699512
TI  - Synergistic effect of programmed cell death protein 1 blockade and secondary
      lymphoid tissue chemokine in the induction of anti-tumor immunity by a
      therapeutic cancer vaccine.
AB  - The use of DNA vaccines has become an attractive approach for generating antigen
      specific cytotoxic CD8+ T lymphocytes (CTLs), which can mediate protective
      antitumor immunity. The potency of DNA vaccines encoding weakly immunogenic tumor
      associated antigens (TAAs) can be improved by using an adjuvant injected together
      with checkpoint antibodies. In the current study, we evaluated whether the
      therapeutic effects of a DNA vaccine encoding human papilloma virus type 16 (HPV
      16) E7 can be enhanced by combined application of an immune checkpoint blockade
      directed against the programmed death-1 (PD-1) pathway and secondary lymphoid
      tissue chemokine (SLC) also known as CCL21 adjuvant, in a mouse cervical cancer
      model. The therapeutic effects of the DNA vaccine in combination with CCL21
      adjuvant plus PD-1 blockade was evaluated using a tumor growth curve. To further
      investigate the mechanism underlying the antitumor response, cytolytic and
      lymphocyte proliferation responses in splenocytes were measured using non
      radioactive cytotoxicity and MTT assays, respectively. Vascular endothelial
      growth factor (VEGF) and IL-10 expression in the tumor and the levels of IFN
      gamma and IL-4 in supernatants of spleno-lymphocyte cultures were measured using
      ELISA. The immune efficacy was evaluated by in vivo tumor regression assay. The
      results showed that vaccination with a DNA vaccine in combination with the CCL21
      adjuvant plus PD-1 blockade greatly enhanced cytotoxic T lymphocyte production
      and lymphocyte proliferation rates and greatly inhibited tumor progression.
      Moreover, the vaccine in combination with adjuvant and blockade significantly
      reduced intratumoral VEGF, IL-10 and splenic IL-4 but induced the expression of
      splenic IFN-gamma. This formulation could be an effective candidate for a vaccine
      against cervical cancers and merits further investigation.

PMID- 27699514
TI  - Coffee consumption and risk of all-cause, cardiovascular, and cancer mortality in
      smokers and non-smokers: a dose-response meta-analysis.
AB  - Coffee consumption has been associated with several benefits toward human health.
      However, its association with mortality risk has yielded contrasting results,
      including a non-linear relation to all-cause and cardiovascular disease (CVD)
      mortality and no association with cancer mortality. As smoking habits may affect
      the association between coffee and health outcomes, the aim of the present study
      was to update the latest dose-response meta-analysis of prospective cohort
      studies on the association between coffee consumption and mortality risk and
      conduct stratified analyses by smoking status and other potential confounders. A
      systematic search was conducted in electronic databases to identify relevant
      studies, risk estimates were retrieved from the studies, and dose-response
      analysis was modeled by using restricted cubic splines. A total of 31 studies
      comprising 1610,543 individuals and 183,991 cases of all-cause, 34,574 of CVD,
      and 40,991 of cancer deaths were selected. Analysis showed decreased all-cause
      [relative risk (RR) = 0.86, 95 % confidence interval (CI) = 0.82, 0.89)] and CVD
      mortality risk (RR = 0.85, 95 % CI = 0.77, 0.93) for consumption of up to 4
      cups/day of coffee, while higher intakes were associated with no further lower
      risk. When analyses were restricted only to non-smokers, a linear decreased risk
      of all-cause (RR = 0.94, 95 % CI = 0.93, 0.96), CVD (RR = 0.94, 95 % CI = 0.91,
      0.97), and cancer mortality (RR = 0.98, 95 % CI = 0.96, 1.00) for 1 cup/day
      increase was found. The search for other potential confounders, including dose
      response analyses in subgroups by gender, geographical area, year of publication,
      and type of coffee, showed no relevant differences between strata. In conclusion,
      coffee consumption is associated with decreased risk of mortality from all-cause,
      CVD, and cancer; however, smoking modifies the observed risk when studying the
      role of coffee on human health.

PMID- 27699515
TI  - A 5-item frailty index based on NSQIP data correlates with outcomes following
      paraesophageal hernia repair.
AB  - BACKGROUND: Frailty is a measure of physiologic reserve associated with increased
      vulnerability to adverse outcomes following surgery in older adults. The
      'accumulating deficits' model of frailty has been applied to the NSQIP database,
      and an 11-item modified frailty index (mFI) has been validated. We developed a
      condensed 5-item frailty index and used this to assess the relationship between
      frailty and outcomes in patients undergoing paraesophageal hernia (PEH) repair.
      METHODS: The NSQIP database was queried for ICD-9 and CPT codes associated with
      PEH repair. Subjects >=60 years who underwent PEH repair between 2011 and 2013
      were included. Five of the 11 mFI items present in the NSQIP data on the most
      consistent basis were selected for the condensed index. Univariate and
      multivariate logistic regressions were used to determine the validity of the 5
      item mFI as a predictor of postoperative mortality, complications, readmission,
      and non-routine discharge. RESULTS: A total of 3711 patients had data for all
      variables in the 5-item index, while 885 patients had complete data to calculate
      the 11-item mFI. After controlling for competing risk factors, including age, ASA
      score, wound classification, surgical approach, and procedure timing (emergent vs
      non-emergent), we found the 5-item mFI remained predictive of 30-day mortality
      and patients being discharged to a location other than home (p < 0.05). A
      weighted Kappa was calculated to assess agreement between the 5-item and 11-item
      mFI and was found to be 0.8709 (p < 0.001). CONCLUSIONS: Frailty, as assessed by
      the 5-item mFI, is a reasonable alternative to the 11-item mFI in patients
      undergoing PEH repair. Utilization of the 5-item mFI allows for a significantly
      increased sample size compared to the 11-item mFI. Further study is necessary to
      determine whether the condensed 5-item mFI is a valid measure to assess frailty
      for other types of surgery.

PMID- 27699516
TI  - Preoperative localization of colorectal cancer: a systematic review and meta
      analysis.
AB  - BACKGROUND: Preoperative colorectal tumor localization is crucial for appropriate
      resection and treatment planning. As the localization accuracy of conventional
      colonoscopy is considered to be low, several localization techniques have been
      developed. We systematically reviewed the tumor localization error rates of
      several preoperative endoscopic techniques and synthesized information on risk
      factors for localization errors and procedure-related adverse events. METHODS:
      MEDLINE, EMBASE, the Cochrane Library, and the grey literature were searched.
      Studies were included if they reported tumor localization errors in patients with
      colorectal cancer undergoing resection with curative intent. Using random-effects
      models, pooled incidence of tumor localization errors were derived for
      conventional colonoscopy and colonoscopic tattooing. Due to the lack of
      comparative studies, a direct comparison of the pooled estimates was performed.
      Procedure-related adverse events, risk factors for localization errors, and the
      localization outcomes of other techniques such as colonoscopic clip placement,
      radioguided occult colonic lesion identification, and the use of magnetic
      endoscope imaging were also synthesized. RESULTS: A total of 38 non-randomized
      controlled and observational studies were included in this review (2578 patients
      underwent conventional colonoscopy and 643 colonoscopic tattooing). The pooled
      incidence of localization errors with conventional colonoscopy was 15.4 % (95 %
      CI 12.0-18.7), whereas that of colonoscopic tattooing was 9.5 % (95 % CI 5.7
      13.3), mean difference 5.9 % (95 % CI 0.65-11.14, p = 0.03). Adverse events
      secondary to tattooing were infrequent, and most were cases of ink spillage.
      Limited information was available for other localization techniques. CONCLUSION:
      Conventional colonoscopy has a higher incidence of localization error compared to
      colonoscopic tattooing for localization of colorectal cancer. Colonoscopic
      tattooing is safe and leads to fewer tumor localization errors. Given the
      widespread adoption of laparoscopic resections for colorectal cancer, routine
      colonoscopic tattooing should be adopted. However, studies directly comparing
      different localization techniques are needed.

PMID- 27699517
TI  - Modified overlap method using knotless barbed sutures (MOBS) for intracorporeal
      esophagojejunostomy after totally laparoscopic gastrectomy.
AB  - BACKGROUND: Compared to end-to-side anastomosis with a circular stapler, the
      overlap method is favored for intracorporeal esophagojejunostomy because it
      facilitates handling of the stapler, even in narrow spaces, and wider
      anastomosis. However, it associates with technical difficulties during
      anastomosis, including difficult traction on the esophageal stump that
      necessitates stay sutures. Here, we introduce a new modified overlap method that
      employs knotless barbed sutures (MOBS) and report the outcomes of our case
      series. METHOD: All consecutive patients who underwent intracorporeal
      esophagojejunostomy in 2015-2016 were included. All patients underwent surgery as
      follows: After esophageal transection with a linear stapler, two V-loc 90 sutures
      (Covidien, Mansfield, MA, USA) were sutured in the center of the stapled line.
      The opening was made between the two threads, and the intraluminal space was
      identified. The jejunum was ascended toward the esophageal stump by inserting a
      45-mm-long linear staple. The anastomosis was made at the space between the right
      and left crura. After firing the linear stapler, the entry hole was closed
      bidirectionally using the pre-sutured threads. RESULTS: Forty patients underwent
      MOBS (27 by laparoscopy; 13 by robot). Mean total operative and MOBS procedural
      times were 180.6 and 22.4 min, respectively. Mean hospital stay was 6.9 days. Two
      patients had major complications (5.0 %). There were no anastomosis-related
      complications. Laparoscopy and robot subgroups did not differ in mean MOBS
      procedural times (22.2 vs. 22.7 min, p = 0.787). CONCLUSION: MOBS is a safe and
      feasible method that is a good option for intracorporeal esophagojejunostomy
      after laparoscopic gastrectomy.

PMID- 27699518
TI  - Long-term outcome of peroral endoscopic myotomy for esophageal achalasia in
      patients with previous Heller myotomy.
AB  - BACKGROUND: Peroral endoscopic myotomy (POEM) is an emerging procedure in the
      treatment of esophageal achalasia, a primary motility disorder. However, the long
      term outcome of POEM in patients, who have previously undergone a Heller myotomy,
      is unknown. METHODS: Using a local database, we identified patients with
      esophageal achalasia, who underwent POEM. We compared patients with a previous
      Heller myotomy to those, who had received none or only non-surgical therapy prior
      to the POEM procedure. We conducted follow-up examinations at 3, 12, and 24
      months following the procedure. RESULTS: We included 66 consecutive patients
      undergoing POEM for achalasia, of which 14 (21.2 %) had undergone a prior Heller
      myotomy. In both groups, the preoperative Eckardt score was 7. Postoperatively,
      the non-Heller group experienced a more pronounced symptom relief at both 3-, 12
      , and 24-month follow-up compared with the Heller group, and there was a tendency
      for the effect of POEM to reduce over time. We suggest that there is a
      correlation between preoperative measurements of gastroesophageal sphincter
      pressures and the chance of a successful POEM. CONCLUSIONS: POEM has a place in
      the treatment of esophageal achalasia in patients with a prior Heller myotomy and
      persistent symptoms as it is a safe procedure with acceptable long-term results.

PMID- 27699519
TI  - Genetic analysis of oriental fruit fly, Bactrocera dorsalis (Diptera:
      Tephritidae) populations based on mitochondrial cox1 and nad1 gene sequences from
      India and other Asian countries.
AB  - The study examined the genetic diversity and demographic history of Bactrocera
      dorsalis, a destructive and polyphagous insect pest of fruit crops in diverse
      geographic regions of India. 19 widely dispersed populations of the fly from
      India and other Asian countries were analysed using partial sequences of
      mitochondrial cytochrome oxidase I (cox1) and NADH dehydrogenase 1 (nad1) genes
      to investigate genetic diversity, genetic structure, and demographic history in
      the region. Genetic diversity indices [number of haplotypes (H), haloptype
      diversity (Hd), nucleotide diversity (pi) and average number of nucleotide
      difference (k)] of populations revealed that B. dorsalis maintains fairly high
      level of genetic diversity without isolation by distance among the geographic
      regions. Demographic analysis showed significant (negative) Tajimas' D and Fu's F
      S with non significant sum of squared deviations (SSD) values, which indicate the
      possibility of recent sudden expansion of species and is further supported
      through distinctively star-like distribution structure of haplotypes among
      populations. Thus, the results indicate that both ongoing and historical factors
      have played important role in determining the genetic structure and diversity of
      the species in India. Consequently, sterile insect technique (SIT) could be a
      possible management strategy of species in the regions.

PMID- 27699520
TI  - Online Radiology Reporting with Peer Review as a Learning and Feedback Tool in
      Radiology; Implementation, Validity, and Student Impressions.
AB  - Communicating radiological reports to peers has pedagogical value. Students may
      be uneasy with the process due to a lack of communication and peer review skills
      or to their failure to see value in the process. We describe a communication
      exercise with peer review in an undergraduate veterinary radiology course. The
      computer code used to manage the course and deliver images online is reported,
      and we provide links to the executable files. We tested to see if undergraduate
      peer review of radiological reports has validity and describe student impressions
      of the learning process. Peer review scores for student-generated radiological
      reports were compared to scores obtained in the summative multiple choice (MCQ)
      examination for the course. Student satisfaction was measured using a bespoke
      questionnaire. There was a weak positive correlation (Pearson correlation
      coefficient = 0.32, p < 0.01) between peer review scores students received and
      the student scores obtained in the MCQ examination. The difference in peer review
      scores received by students grouped according to their level of course
      performance (high vs. low) was statistically significant (p < 0.05). No
      correlation was found between peer review scores awarded by the students and the
      scores they obtained in the MCQ examination (Pearson correlation coefficient =
      0.17, p = 0.14). In conclusion, we have created a realistic radiology imaging
      exercise with readily available software. The peer review scores are valid in
      that to a limited degree they reflect student future performance in an
      examination. Students valued the process of learning to communicate radiological
      findings but do not fully appreciated the value of peer review.

PMID- 27699521
TI  - Longitudinal change in choroidal thickness after trabeculectomy in primary open
      angle glaucoma patients.
AB  - PURPOSE: To investigate longitudinal changes in intraocular pressure (IOP), axial
      length (AL), and choroidal thickness (ChT) in primary open-angle glaucoma (POAG)
      eyes after trabeculectomy and to evaluate the parameters that might influence
      those changes. METHODS: In this prospective observational study, we recruited 28
      patients with POAG (28 eyes) scheduled for trabeculectomy. The average macular
      ChTs and foveal retinal thicknesses along 6-mm segments centered on the fovea
      were examined preoperatively and postoperatively (at 1, 3, and 6 months) using
      swept-source optical coherence tomography. The IOP, AL, and mean deviation (MD)
      of standard automated perimetry (SAP) were also analyzed as independent
      variables. RESULTS: Results from 16 patients were included in the final analysis.
      A significant increase in ChT with respect to the preoperative value was observed
      at every postoperative stage (1 month, P < 0.001; 3 months, P < 0.001; 6 months,
      P = 0.011), whereas the retinal thickness showed no significant change over the
      study period. The ChT increase and IOP reduction were sustained throughout the 6
      month period without further significant changes. Stepwise multivariate analyses
      showed significant correlations between the percentage decrease in IOP and the
      percentage increase in ChT at 1 and 6 months postoperatively. The percentage
      increase in ChT was also significantly correlated with a better MD of the SAP at
      1 month (beta = 0.01; P = 0.009). CONCLUSIONS: The ChT increase following
      trabeculectomy was sustained at 1, 3, and 6 months postoperatively. The
      percentage increase in ChT was significantly correlated with the percentage
      change in IOP and (more weakly) with better SAP MD values.

PMID- 27699522
TI  - Eyelid cleansing with ointment for obstructive meibomian gland dysfunction.
AB  - PURPOSE: To investigate the efficacy of eyelid margin cleansing with ofloxacin
      ophthalmic ointment in obstructive meibomian gland dysfunction (MGD) patients.
      METHODS: Thirty-one eyes of 31 patients diagnosed with obstructive MGD were
      enrolled. All subjects were instructed to rub the eyelid edge with ofloxacin eye
      ointment once daily prior to bathing. Lid margin abnormalities, meibum
      properties, and tear stability were observed before and 3 months after ointment
      treatment. A questionnaire relating to the severity of MGD symptoms was
      administered after the treatment. RESULTS: Vascular engorgement, meibum, dandruff
      like debris, and fluorescein staining scores significantly decreased after the
      treatment, whereas tear break-up time significantly increased (p < 0.05).
      Symptoms related to MGD improved after the treatment in 86.2 % of cases.
      CONCLUSIONS: Cleansing treatment ofloxacin ophthalmic ointment at the eyelid
      margin may be effective for patients with obstructive MGD.

PMID- 27699523
TI  - Phenotypic variability of Dent disease in a large New Zealand kindred.
AB  - BACKGROUND: Dent disease 1 is a rare cause of chronic kidney disease (CKD) in
      childhood secondary to mutations in the gene encoding the chloride-proton
      exchanger, CLC-5, which is found mainly in the proximal tubule. Clinical
      manifestations are variable and there are no known genotype-phenotype
      correlations. CASE DIAGNOSIS/TREATMENT: The proband was identified as having a
      mutation in CLCN5. The extended family of the proband was invited to participate
      in a study of Dent disease after several males were noted to have a history of
      CKD. Urine retinol binding protein, urine calcium, serum creatinine, and DNA
      samples were collected for analysis. Ten hemizygous males and 6 heterozygous
      females were identified. Advanced CKD was detected in 3 males (1 child). Renal
      biopsies in 4 children showed both glomerular and tubulo-interstitial changes.
      There was no correlation between age and disease severity. CONCLUSIONS: This is
      the first reported family from the southern hemisphere with this condition. A
      novel CLCN5 mutation is described, c.1618G>C (p.Ala540Pro). The severity of renal
      disease varies greatly among individuals.

PMID- 27699525
TI  - Psychological Distress as an Indicator of Co-Occurring Psychopathology among
      Treatment-Seeking Disordered Gamblers.
AB  - Disordered gamblers frequently present with concurrent anxiety, depressive,
      personality, and substance use disorders, which may complicate treatment.
      Although there is a need for a thorough assessment, some questionnaires may prove
      lengthy for clients and clinicians. Thus, there is a need for brief screens for
      identifying co-occurring psychopathology. The present study sought to examine
      whether a brief, self-report measure of psychological distress could indicate the
      presence of co-occurring psychopathology among an outpatient sample of disordered
      gamblers. At intake, 69 participants completed self-report measures of distress
      and gambling symptomatology, a personality inventory, and a structured interview
      for the diagnostic criteria for disordered gambling. Gamblers with greater
      elevations of psychological distress evidenced greater severity of gambling
      pathology. Clinically significant elevations were present for symptoms of
      depression, deviancy, and anxiety, but not substance abuse. Greater scores of
      psychological distress significantly predicted elevations of depression,
      deviancy, and anxiety. Sensitivity and specificity were evaluated and the
      findings supported that an average psychological distress score of 16
      corresponded with the presence of co-occurring psychopathology. Clinicians
      treating disordered gamblers should consider screening for co-occurring
      psychopathology with brief, self-report measures of psychological distress.

PMID- 27699524
TI  - Solid state NMR of isotope labelled murine fur: a powerful tool to study atomic
      level keratin structure and treatment effects.
AB  - We have prepared mouse fur extensively 13C,15N-labelled in all amino acid types
      enabling application of 2D solid state NMR techniques which establish covalent
      and spatial proximities within, and in favorable cases between, residues. 13C
      double quantum-single quantum correlation and proton driven spin diffusion
      techniques are particularly useful for resolving certain amino acid types. Unlike
      1D experiments on isotopically normal material, the 2D methods allow the chemical
      shifts of entire spin systems of numerous residue types to be determined,
      particularly those with one or more distinctively shifted atoms such as Gly, Ser,
      Thr, Tyr, Phe, Val, Leu, Ile and Pro. Also the partial resolution of the amide
      signals into two signal envelopes comprising of alpha-helical, and beta
      sheet/random coil components, enables resolution of otherwise overlapped alpha
      carbon signals into two distinct cross peak families corresponding to these
      respective secondary structural regions. The increase in resolution conferred by
      extensive labelling offers new opportunities to study the chemical fate and
      structural environments of specific atom and amino acid types under the influence
      of commercial processes, and therapeutic or cosmetic treatments.

PMID- 27699527
TI  - Epidemiology of HPV-Positive Tumors in Europe and in the World.
AB  - Strong evidence has accumulated in the last 15 years showing that infection by
      certain human papillomaviruses (HPVs) is etiologically involved in a subset of
      head and neck cancers (HNCs). In this chapter, epidemiologic-related topics on
      HNCs are reviewed: (i) HPV-attributable fractions and HPV-type distributions by
      different anatomical HNC sites, using not only HPV DNA but other more specific
      markers of causality; (ii) an update of the HPV-related HNCs burden worldwide and
      by regions; and finally, (iii) the determinants for HPV positivity in HNCs,
      focussing on gender, age, smoking habits, sexual behavior, and other related
      factors such as tonsillectomy performance. This information is essential in order
      to understand the burden of the disease and its dynamics and changing patterns,
      as well as for planning and assessment of the potential impact of HPV-based
      preventive strategies for HNCs.

PMID- 27699526
TI  - HPV in Head and Neck Cancer-30 Years of History.
AB  - The interesting history of papillomavirus (PV) research has been reviewed before.
      The history of human papillomavirus (HPV) in head and neck region starts in 1901
      when the contagious transmission of warty lesions into the mouth via oral sex was
      described, although the confirmation of their viral etiology had to wait until
      1907. Ullman was the first to associate the human wart virus with laryngeal
      warts. Parsons and Kidd described the natural history of oral PV infections in
      rabbits already in 1942, but these findings were corroborated in humans only
      recently. Koilocytotic atypia described by Koss and Durfee in 1956 was recognized
      as a sign of HPV infection in cervical precancer lesions only in 1976-1977
      (Meisels and Fortin; Purola and Savia). This prompted systematic surveys of head
      and neck lesions for the detection of koilocytosis since the late 1970s, and the
      authors of this communication were the first to propose the HPV involvement in a
      subgroup of head and neck cancers. Brandsma and Abramson demonstrated HPV16 DNA
      in tonsillar SCCs in 1989. Since the early 2000s, HPV research of head and neck
      squamous cell carcinomas (HNSCC) has made impressive progress, confirming that
      the specific anatomic site plays a key role in determining the susceptibility to
      HPV infection. The most likely cancer sites associated with HPV are the base of
      the tongue and palatine tonsils, followed by oral cavity, larynx, and sinonasal
      mucosa. There is substantial geographic variation in HPV association with HNSCC.
      Patients with HPV-associated HNSCC are younger, and survival is better than in
      the absence of HPV.

PMID- 27699528
TI  - Molecular Patterns and Biology of HPV-Associated HNSCC.
AB  - Head and neck cancer is the sixth most common cancer worldwide. The large
      majority are squamous cell carcinomas (HNSCC) that develop in the mucosal linings
      of the upper aerodigestive tract. These tumors develop either by exogenous
      carcinogen exposure (smoking, alcohol drinking) or by human papillomavirus (HPV)
      infection, particularly those in the oropharynx (OPSCC). HPV-positive (HPV+ve)
      and HPV-negative (HPV-ve) OPSCC are considered different disease entities. HPV+ve
      tumors are different at the molecular level and likely as a consequence have a
      much more favorable prognosis than HPV-ve tumors, despite their generally
      advanced stage at presentation. In general, HNSCCs develop in precancerous
      mucosal changes, and the apparent lack of precancerous HPV+ve mucosal changes is
      therefore remarkable. In this Chapter, head and neck carcinogenesis is discussed
      and the molecular differences between HPV+ve and HPV-ve tumors are outlined.

PMID- 27699529
TI  - HPV Integration in Head and Neck Squamous Cell Carcinomas: Cause and Consequence.
AB  - Human papillomaviruses (HPVs) are a necessary cause of anogenital squamous cell
      carcinomas (SCC) and a subgroup of head and neck SCC, i.e., those originating in
      the oropharynx. The key events in high-risk HPV (HRHPV)-associated neoplastic
      progression include persistent infection, deregulated expression of virus early
      genes in basal epithelial cells, local immune suppression and the accumulation of
      chromosomal alterations. Evidence for these events particularly comes from
      studies of uterine cervical carcinogenesis; primary premalignant HRHPV-positive
      lesions of the head and neck mucosa are seldomly detected. Integration of virus
      DNA into host chromosomes is considered an important driver of carcinogenesis and
      observed in 40 up to 90 % of uterine cervical SCC (UCSCC) and oropharyngeal SCC
      (OPSCC), dependent on the integration detection method used and HRHPV type. In
      OPSCC, > 90 % HPV-positive tumors are infected with HPV16. Ten up to 60 % of HPV
      positive tumors thus contain extrachromosomal (episomal) virus. In this chapter,
      causes and consequences of HPV integration are summarized from the literature,
      with special focus on the site of HPV integration in the cellular genome, and its
      effect on expression of viral oncogenes (particularly E6 and E7), on human
      (tumor) gene expression and on deregulation of cell proliferation, apoptosis and
      cell signaling pathways. Also data on DNA methylation, viral load and clinical
      outcome in relation to HPV integration are provided.

PMID- 27699530
TI  - Risk Factors for Oral Infection with Human Papillomavirus.
AB  - Human papillomavirus has been identified as a causative factor for a subset of
      head and neck carcinomas (HNSCC). The majority of the HPV-positive tumors arises
      in the oropharyngeal region, and at present, the infection of the human papilloma
      type 16 is the major cause of the oropharyngeal cancer development. Patients with
      HPV DNA-positive tumors have been shown to be younger in age and are less likely
      to have a history of tobacco smoking or alcohol use. The tumors referred to the
      HPV positivity have been proven to more likely confer better prognosis. Seven
      percent of the population between ages of 14 and 69 are infected by HPV at any
      given time within the oral mucosa. However, only about 1 % of those infections is
      associated with the high-risk cancerogenous types of the virus. Up to date few
      risk factors of HPV infection have been identified including age, gender and the
      sexual behavior. Tobacco smoking and immunosuppression have also been reported to
      play a role in HPV infection.

PMID- 27699531
TI  - HPV-Related Head and Neck Squamous Cell Carcinomas.
AB  - Since more than 5 years, it becomes evident that there is a new group of patients
      with squamous cell carcinomas of the head and neck area, namely human
      papillomavirus (HPV)-related (caused) tumors. As clinical statistics indicate,
      those patients have better prognosis, even despite more advanced stage compared
      to those with HPV-negative tumors. In fact, as a surrogate of HPV infection for
      clinical studies, an immunohistochemical expression of p16 protein is used. In
      the following chapter, the spectrum of squamous cell carcinomas variants with
      indication of the percentage cases with proved HPV infection will be presented.

PMID- 27699532
TI  - HPV Testing of Head and Neck Cancer in Clinical Practice.
AB  - The pathology laboratory has a central role in providing human papillomavirus
      (HPV) tests for patients with head and neck cancer. There is an extensive
      literature around HPV testing and a large number of proprietary HPV tests, which
      makes the field difficult to navigate. This review provides a concise
      contemporary overview of the evidence around HPV testing in head and neck cancer
      and signposts key publications, guideline documents and the most commonly used
      methods in clinical practice.

PMID- 27699533
TI  - Variation of HPV Subtypes with Focus on HPV-Infection and Cancer in the Head and
      Neck Region.
AB  - The human papillomavirus (HPV) comprises a heterogeneous group of double-strand
      DNA viruses with variable potential to infect human epithelial cells and trigger
      neoplastic transformation. Its 8 kb genome encodes proteins required for virus
      replication and self-organized formation of infectious particles but also for
      early proteins E6 and E7 able to trigger neoplastic transformation. E6 and E7 of
      high-risk (HR) HPV subtypes can bind to p53 or release E2F and abrogate
      replication control. Due to variable amino acid sequence (AAS) in the binding
      sites of E6 and E7 particular HR-HPV variants within subtypes are essentially
      heterogeneous in efficacy triggering neoplastic transformation and cancer
      development. This could explain differences in the clinical course of HPV-driven
      head and neck cancer.

PMID- 27699534
TI  - Tumor Staging and HPV-Related Oropharyngeal Cancer.
AB  - The current TNM staging for oropharyngeal cancer (OSCC) was designed empirically
      for non-HPV-related disease. Emerging evidence suggests it is unsuited for Human
      papillomavirus (HPV)-related OSCC. Patients with HPV-positive tumors have
      improved prognosis, despite presenting at advanced stages. These shortcomings of
      the current staging system have been identified in single- and multi
      institutional trials. Patients with HPV related OSCC typically present with
      advanced N-stages leading to higher stage groupings. A rarity of stages I and II
      therefore represents the nature of HPV-related OSCC. Concerning prognosis of the
      patients, N-category and extracapsular spread seem to be of minor importance,
      whereas advanced T-stages result in unfavourable outcome. Anatomical staging
      therefore has been implied into different proposals to prognostic risk
      classifications in HPV-related disease as an additive compound. Prognostic risk
      groupings are further enhanced by incorporating non-anatomical factors. To
      summarize, it can be suggested that the current TNM system alone has little
      prognostic value in HPV-related OSCC.

PMID- 27699535
TI  - Human Papillomavirus (HPV): A Criterion for Therapeutic Decision in Squamous Cell
      Carcinoma of the Head and Neck?
AB  - When deciding how to treat patients with squamous cell carcinoma of the head and
      neck (SCCHN), several factors have to be taken into account: disease factors,
      patient factors, treatment factors, and the wish of the patient. This symposium
      article is summarizing the information on HPV (p16) in the context of decision
      making in SCCHN patients with locoregionally advanced disease and those with
      recurrent/metastatic disease. The literature data suggest that HPV(p16) has
      prognostic significance, both in locoregionally advanced disease (in particular,
      in oropharynx cancer) and in recurrent/metastatic disease, while there are only
      limited data on its predictive significance. Results of HPV (p16) testing should
      not change management outside clinical trials.

PMID- 27699536
TI  - Systemic Treatment in HPV-Induced Recurrent or Metastatic HNSCC.
AB  - Recurrent or metastatic head and neck cancer describes tumor deposits that arise
      locally, regionally, or at distant sites after treatment or distant metastases at
      the time of primary diagnosis. Prognosis for R/M squamous cell carcinomas of the
      head and neck (HNSCC) is poor and treatment options are limited in this
      situation. Human papillomavirus (HPV) is an important risk factor for HNSCC.
      About 40 % of all HNSCC have been attributed to HPV in Europe. HPV positivity at
      initial diagnosis is the single best prognostic factor for survival. However,
      data for the prognostic and predictive value of HPV in the R/M situation are
      still scarce. Due to the rising incidence of HPV-associated cancers, the number
      of R/M HPV+ carcinomas is also expected to rise. This chapter therefore aims to
      give an overview of the current knowledge concerning the role of HPV as a
      prognostic and predictive marker in recurrent or metastatic HNSCC.

PMID- 27699537
TI  - Optimizing Radiotherapy in HPV-Associated Oropharyngeal Cancer Patients.
AB  - Concurrent chemoradiation is considered the golden standard in the treatment of
      locally advanced OPC. However, given the very high survival rates in favorable
      HPV-positive OPC and the high rates of acute and late treatment-related side
      effects, de-escalation strategies have to be considered. In this chapter, the
      potential benefit of a number of de-escalation strategies is described, including
      of replacement of concurrent chemotherapy by cetuximab, radiation dose de
      escalation based on response to induction chemotherapy, radiotherapy alone
      without systemic treatment, and limiting elective nodal target volumes for
      radiation. In addition to de-escalation, modern radiation technologies like
      protons will offer increasing opportunities to decrease the dose to normal
      tissues in order to prevent radiation-induced toxicities. Initial analysis showed
      that radiation dose de-escalation based on response to induction chemotherapy in
      combination with intensity-modulated proton therapy (IMPT) has the highest
      potential to decrease acute and late toxicities.

PMID- 27699538
TI  - Should We De-escalate the Treatment for HPV-Positive Tumors?
AB  - De-escalation or de-intensification of therapy is discussed since many
      retrospective analyses of former trials demonstrated significantly better outcome
      for patients suffering from p16/HPV16-positive oropharyngeal squamous cell
      carcinoma of head and neck (OHNSCC). These observations are comprehensively
      addressed, but the reader has to keep in mind that none of the currently
      discussed data result from prospective controlled trials addressing the HPV
      discrimination in the primary endpoint design. Identification of the true HPV16
      related tumors is still challenging and in addition with different clinical
      reports and lack of data of prospective trials not mature for routine clinical
      decision making in 2016. Independent of the currently lacking evidence for HPV
      dependent treatment de-escalation, there are some relevant arguments to address
      this question in ongoing and future trials.

PMID- 27699539
TI  - The Role of Conventional Surgery in Oropharyngeal Cancer.
AB  - Anatomically, the oropharynx can be divided into four subsites: the soft palate,
      pharyngeal wall, base of tongue, and the tonsillar complex. Surgical access to
      these tumours is often challenging due to the anatomic localization. For this
      reason, such tumours were traditionally managed with open surgical techniques,
      usually involving a mandibulotomy, to provide better visualization and access to
      the oropharynx, followed by free-flap reconstruction of the oropharyngeal defect.
      However, the invasiveness of this approach could lead to significant morbidity,
      including speech, swallowing, and airway dysfunction, in addition to poor
      cosmetic outcomes. In response, less invasive approaches (Mercante et al. 2013)
      have been developed including minimally invasive surgical approaches (chiefly
      transoral surgery) as well as non-surgical methods, primarily radiotherapy, and
      chemotherapy (Mercante et al. 2013).

PMID- 27699540
TI  - The Role of Surgery in the Management of Recurrent Oropharyngeal Cancer.
AB  - The incidence of oropharyngeal squamous cell carcinoma (OPSCC) continues to rise
      worldwide at a dramatic pace, buoyed by the predominance of human papilloma virus
      (HPV) driven disease (Panwar et al. 2014). While the outcomes of patients with
      HPV-positive OPSCC are dramatically improved compared to HPV-negative OPSCC,
      treatment failures do occur. The result is an inevitable rise in the incidence of
      recurrent OPSCC. Since the majority of incident OPSCC cases are treated with some
      form of radiation therapy (primary or adjuvant), surgery remains the backbone of
      treatment for recurrent OPSCC. This section will focus on options for surgical
      management of recurrent OPSCC.

PMID- 27699541
TI  - TORS in HPV-Positive Tumors-The New Standard?
AB  - In this chapter, we discuss implications of tumor site and tumor microenvironment
      properties of human papilloma virus (HPV)-associated cancer formation with
      special emphasis on the therapeutic modality of transoral robotic surgery (TORS).
      Over the past years, the development of robotic systems has improved, and
      therefore, its use in the surgical treatment of HNSCC has become a relevant
      treatment modality for many patients. Yet, there are limitations. Especially for
      endolaryngeal TORS procedures, additional technical development is mandatory,
      particularly with respect to visualization and manipulation. The Flex System has
      provided new additions that need to be further evaluated. TORS systems are going
      to improve technical issues and therefore reduce patient morbidity, surgical
      handling and treatment costs. The developed systems have to be tested and
      evaluated in prospective trials in order to be able to identify benefits and
      disadvantages in patient care. With respect to HPV-related OPSCC, TORS has become
      a valuable surgical alternative for an increasing number of patients.

PMID- 27699542
TI  - Risk Groups for Survival in HPV-Positive and HPV-Negative OPSCC.
AB  - Over the last three decades, it has become clear that infection with high-risk
      human papillomavirus (HPV) is etiologically linked to the development of head and
      neck squamous cell carcinomas, particularly those carcinomas that arise in the
      oropharyngeal region.

PMID- 27699544
TI  - Cancer Immunology and HPV.
AB  - HNSCC is a heterogeneous group of tumors located in the oral cavity, oropharynx,
      hypopharynx and larynx. Originally, tobacco and alcohol exposures were the main
      risk factors for HNSCC. In the last two decades, HPV infections have been
      identified as a risk factor for HNSCC, especially for oropharyngeal tumors.
      Whereas the HPV-induced oropharyngeal carcinomas predominantly express the HPV16
      related E6 and E7 oncoproteins, the HPV-negative HNSCC are associated with an
      overexpression of p53. However, if the therapy successes for HPV-negative and HPV
      positive HNSCCs are compared, there are significantly higher total survival rates
      for HPV-positive oropharyngeal tumors compared to HPV-negative tumors. It is
      important to understand this phenomenon in order to improve and adapt therapy
      concepts.

PMID- 27699543
TI  - Predictive Factors for Outcome and Quality of Life in HPV-Positive and HPV
      Negative HNSCC.
AB  - Infection with high-risk types of the human papilloma virus (HPV) is an
      etiological risk factor for oropharyngeal squamous cell carcinoma (OPSCC) and
      associated with a better response to therapy and improved survival. A better
      understanding of the molecular principles underlying the differences in clinical
      behavior could pave the way to establish more effective and less toxic therapy
      for HPV-positive OPSCC and their HPV-negative counterparts. Compelling
      experimental evidence demonstrates that extensive global reprogramming of
      epigenetic profiles is as important as genetic mutations during neoplastic
      transformation and malignant progression, including HPV-positive OPSCC. In this
      chapter, the current knowledge on HPV-related alterations in DNA methylation,
      histone modification, and chromosome remodeling will be summarized and assessment
      of cancer-related profiles will be discussed as a valuable tool to gain important
      diagnostic or prognostic information for therapeutic decision-making and clinical
      management of HNSCC patients.

PMID- 27699545
TI  - Update on De-intensification and Intensification Studies in HPV.
AB  - In this chapter, we discuss de-esclation of treatment for patients with HPV
      positive disease. We discuss the rationale for de-escalation (why de-escalate?),
      patient selection criteria (who to de-esclate?) and what the treatment options
      for de-esclation are and the studies that are currently being run in those areas
      (how to de-escalate?). We stress the importance of clinicians NOT changing the
      management of oropharyngeal cancer patients outside clinical trials, and
      encourage them to recruit to the ongoing studies.

PMID- 27699546
TI  - Vaccination Expectations in HNSCC.
AB  - HPV-associated head and neck squamous cell carcinoma (HNSCC), more specifically
      the incidence of oropharyngeal cancer, is dramatically increasing in
      industrialized countries. According to what has been learned from anogenital
      vaccination programs, there are reasons to believe that current human
      papillomavirus (HPV) vaccinations may be potentially effective also against
      HNSCC. However, before specific results on HNSCC are available, one must keep in
      mind that carcinogenesis in the head and neck region may differ from that of the
      anogenital tract. Furthermore, the current evidence supports the view that HPV
      infection is much more complex than simply a sexually transmitted disease. HPV is
      present in the semen, placenta and in the newborns, and these infections of the
      newborns create cell-mediated immunity (CMI) against HPV, including the T memory
      cells. Acquisition of HPV infection in early life will rise new series of
      questions in the field of HPV vaccination.

PMID- 27699550
TI  - Continuation of direct oral anticoagulants in the acute phase of ischemic stroke.
      A case series.

PMID- 27699551
TI  - Improving the hydrogen storage properties of metal-organic framework by
      functionalization.
AB  - Based on the structure of MOF-808, different substituents were introduced to
      replace hydrogen atom on the phenyl ring of MOF-808. The GCMC method was used to
      study the effect of functional groups on the hydrogen storage properties of MOF
      808-X (X = -OH, -NO2, -CH3, -CN, -I). The H2 uptakes and isosteric heat of
      adsorption were simulated at 77 K. The results indicate that all these
      substituents have favorable impact on the hydrogen storage capacity, and -CN is
      found to be the most promising substituent to improve H2 uptake. These results
      may be helpful for the design of MOFs with higher hydrogen storage capacity.
      Graphical abstract Atomistic structures of MOFs. (a) The structures of MOF-808-X.
      (b) Model of organic linker. Atom color scheme: C, gray; H, white; O, red; X,
      palegreen (X = -OH, -NO2, -CH3, -CN, -I).

PMID- 27699552
TI  - Synthesis, electronic, and spectral properties of novel geranylated chalcone
      derivatives: a theoretical and experimental study.
AB  - Novel chalcone derivatives with different substituents attached to A and B-rings:
      hydroxyl, methoxyl, geranyl, and prenyl groups were synthesized. The obtained
      compounds were characterized by NMR, HRMS, UV-Vis, IR, and MS. The theoretical
      analysis was carried out in all the compounds using density functional theory
      (DFT) with the B3LYP, PBE0, and M06-2X functionals in combination with the 6
      311G(d,p) Pople-type basis set. The excited state properties were calculated by
      time dependent density functional theory (TD-DFT) using the same methodology
      applied for the ground state properties. The calculated vertical absorption
      wavelengths (lambdamax) in gas phase and in ethanol as a solvent are consistent
      with the experimental ones, being the TD-DFT:B3LYP/6-311G(d,p) and PCM-TD
      DFT:PBE0/6-311G(d,p) the best methodologies for these calculations with good
      approximation to the experimental values. The calculated reorganization energies
      indicated that, the four chalcone derivatives present an electron transfer
      character due to the smaller registered values. From these parameters it is
      proposed that these show an n-type semiconductor character. The localization of
      the frontier orbitals (HOMO and LUMO) shows that only the compound containing a
      hydroxyl group on the A-ring displays a marked delocalization favoring the charge
      transfer process in this system. The HOMO-LUMO gap energies indicate that the
      inclusion of different donor groups in the rings does not improve the obtained
      values for this property. Graphical Abstract Relationship between spectroscopic
      and geometrical properties of chalcones were carried out using quantum-chemical
      calculations and compared with experimental values.

PMID- 27699553
TI  - On the fly estimation of host-guest binding free energies using the movable type
      method: participation in the SAMPL5 blind challenge.
AB  - We review our performance in the SAMPL5 challenge for predicting host-guest
      binding affinities using the movable type (MT) method. The challenge included
      three hosts, acyclic Cucurbit[2]uril and two octa-acids with and without
      methylation at the entrance to their binding cavities. Each host was associated
      with 6-10 guest molecules. The MT method extrapolates local energy landscapes
      around particular molecular states and estimates the free energy by Monte Carlo
      integration over these landscapes. Two blind submissions pairing MT with variants
      of the KECSA potential function yielded mean unsigned errors of 1.26 and 1.53
      kcal/mol for the non-methylated octa-acid, 2.83 and 3.06 kcal/mol for the
      methylated octa-acid, and 2.77 and 3.36 kcal/mol for Cucurbit[2]uril host. While
      our results are in reasonable agreement with experiment, we focused on particular
      cases in which our estimates gave incorrect results, particularly with regard to
      association between the octa-acids and an adamantane derivative. Working on the
      hypothesis that differential solvation effects play a role in effecting computed
      binding affinities for the parent octa-acid and the methylated octa-acid and that
      the ligands bind inside the pockets (rather than on the surface) we devised a new
      solvent accessible surface area term to better quantify solvation energy
      contributions in MT based studies. To further explore this issue a, molecular
      dynamics potential of mean force (PMF) study indicates that, as found by our
      docking calculations, the stable binding mode for this ligand is inside (rather
      than surface bound) the octa-acid cavity whether the entrance is methylated or
      not. The PMF studies also obtained the correct order for the methylation-induced
      change in binding affinities and associated the difference, to a large extent to
      differential solvation effects. Overall, the SAMPL5 challenge yielded in
      improvements our solvation modeling and also demonstrated the need for thorough
      validation of input data integrity prior to any computational analysis.

PMID- 27699554
TI  - Molecular docking performance evaluated on the D3R Grand Challenge 2015 drug-like
      ligand datasets.
AB  - The D3R Grand Challenge 2015 was focused on two protein targets: Heat Shock
      Protein 90 (HSP90) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4
      (MAP4K4). We used a protocol involving a preliminary analysis of the available
      data in PDB and PubChem BioAssay, and then a docking/scoring step using more
      computationally demanding parameters that were required to provide more reliable
      predictions. We could evidence that different docking software and scoring
      functions can behave differently on individual ligand datasets, and that the
      flexibility of specific binding site residues is a crucial element to provide
      good predictions.

PMID- 27699555
TI  - Adjuvant radiation use in older women with early-stage breast cancer at Johns
      Hopkins.
AB  - PURPOSE: In 2004, The National Comprehensive Cancer Network (NCCN) Guidelines
      incorporated omission of radiation therapy after breast-conservation surgery in
      women >=70 years old with stage I, estrogen receptor-positive breast cancer who
      plan to receive endocrine therapy. One study demonstrated wide variation in
      implementing this change across 13 NCCN institutions. We evaluated the practice
      pattern at our institution. METHODS: We identified women >=70 years old treated
      at our institution from 2009 to 2014. We calculated radiation therapy omission
      rate in those meeting the guidelines. We explored associations between radiation
      therapy omission, year of diagnosis, and patient characteristics with Wilcoxon
      rank sum tests and Fisher's exact tests. RESULTS: A total of 667 women met the
      inclusion criteria, and 117 (18 %) were candidates for radiation therapy
      omission. Mean age among the 117 was 76.3 years (Range: 70-95). Overall radiation
      therapy omission rate was 36.8 %, but varied greatly by year of diagnosis (Range:
      7.7-54.5 %). This variation persisted after excluding women who did not receive
      endocrine therapy (Mean: 39.0 %, Range: 0.0-75.0 %). Factors associated with
      higher radiation therapy omission rates included older age and not having
      pathological nodal evaluation. The radiation therapy omission rate did not vary
      by race, tumor type, grade, or size. CONCLUSIONS: The implementation of the NCCN
      guideline has not been consistent at our institution. Our data suggest that other
      tools should be considered to apply the guidelines more consistently. We have
      implemented a quality improvement protocol that incorporates life expectancy
      estimate and geriatric assessment in women meeting the NCCN guideline at our
      institution.

PMID- 27699556
TI  - Testing whether patients with diabetes and healthy people perceive the meaning of
      the items in the Persian version of the SF-36 questionnaire similarly: a
      differential item functioning analysis.
AB  - PURPOSE: It has been rarely studied whether observed disparity in health-related
      quality-of-life (HRQoL) scores between patients with diabetes and healthy
      individuals is due to differential item functioning (DIF) or a true difference in
      the underlying construct. This study aimed to examine DIF in the SF-36
      questionnaire and its effect on comparing HRQoL scores between patients with
      diabetes and healthy people. METHODS: The sample consisted of 230 patients with
      type 2 diabetes and 642 healthy individuals who filled out the Persian version of
      the SF-36 questionnaire. To detect DIF across patients with diabetes and healthy
      individuals, multiple-group multiple-indicator multiple-causes model was used. In
      addition, item calibration strategy was used to determine whether the effect of
      item-level DIF was transferred to the scale level. RESULTS: Nine out of thirty
      six (25 %) items were detected as DIF, of which one item (11 %) was flagged as
      uniform and eight items (89 %) as non-uniform DIF. Most of the DIF items were
      detected in the mental health component which includes vitality, perceived mental
      health and social functioning subscales rather than in physical health component.
      Moreover, nonsignificant latent mean differences for general health perception
      and social functioning subscales became significant after DIF calibration.
      CONCLUSION: The findings of the present study show that patients with diabetes
      and healthy individuals perceived some items in the SF-36 questionnaire
      differently. More importantly, in some subscales, the effect of item-level DIF
      was transferred to the scale level. Consequently, considerable caution should be
      taken in comparing HRQoL scores between patients with diabetes and healthy
      individuals.

PMID- 27699557
TI  - Oral health-related quality of life in youth receiving cleft-related surgery:
      self-report and proxy ratings.
AB  - PURPOSE: This paper evaluated the impact of cleft-related surgery on the oral
      health-related quality of life (OHRQoL) of youth with cleft over time. METHODS:
      Data were derived from a 5-year, multi-center, prospective, longitudinal study of
      1196 youth with cleft lip and/or palate and their caregivers. Eligible youth were
      between 7.5 and 18.5 years old, spoke English or Spanish, and were non-syndromic.
      During each observational period, which included baseline, and 1- and 2-year post
      baseline follow-up visits, youths and their caregivers completed the Child Oral
      Health Impact Profile, a validated measure of OHRQoL. Multilevel mixed-effects
      models were used to analyze the effects of receipt of craniofacial surgery on
      OHRQoL over time. RESULTS: During the course of this study a total of 516
      patients (43 %) received at least one surgery. Youth in the surgery
      recommendation group had lower self- (beta = -2.18, p < 0.05) and proxy-rated
      (beta = -2.92, p < 0.02) OHRQoL when compared to non-surgical self- and proxy
      rated OHRQoL at baseline. Both surgical and non-surgical youth (beta = 3.73, p <
      0.001) and caregiver (beta = 1.91, p < 0.05) ratings of OHRQoL improved over
      time. There was significant incremental improvement (time * surgery interaction)
      in self-reported OHRQoL for youth postsurgery (beta = 1.04, p < 0.05), but this
      postsurgery increment was not seen in the caregiver proxy ratings. CONCLUSIONS:
      Surgical intervention impacts OHRQoL among youth with cleft. Youth who were
      surgical candidates had lower baseline self- and caregiver-rated OHRQoL when
      compared to non-surgical youth. Youth who underwent cleft-related surgery had
      significant incremental improvements in self-rated but not caregiver (proxy)
      rated OHRQoL after surgery.

PMID- 27699559
TI  - Multiple Equating of Separate IRT Calibrations.
AB  - When test forms are calibrated separately, item response theory parameters are
      not comparable because they are expressed on different measurement scales. The
      equating process includes the conversion of item parameter estimates on a common
      scale and the determination of comparable test scores. Various statistical
      methods have been proposed to perform equating between two test forms. This paper
      provides a generalization to multiple test forms of the mean-geometric mean, the
      mean-mean, the Haebara, and the Stocking-Lord methods. The proposed methods
      estimate simultaneously the equating coefficients that permit the scale
      transformation of the parameters of all forms to the scale of the base form.
      Asymptotic standard errors of the equating coefficients are derived. A simulation
      study is presented to illustrate the performance of the methods.

PMID- 27699558
TI  - Item Cloning Variation and the Impact on the Parameters of Response Models.
AB  - Item cloning is increasingly used to generate slight differences in tasks for use
      in psychological experiments and educational assessments. This paper investigates
      the psychometric issues that arise when item cloning introduces variation into
      the difficulty parameters of the item clones. Four models are proposed and
      evaluated in simulation studies with conditions representing possible types of
      variation due to item cloning. Depending on the model specified, unaccounted
      variance in the item clone difficulties propagates to other parameters in the
      model, causing specific and predictable patterns of bias. Person parameters are
      largely unaffected by the choice of model, but for inferences related to the item
      parameters, the choice is critical and can even be leveraged to identify
      problematic item cloning.

PMID- 27699560
TI  - On the Finiteness of the Weighted Likelihood Estimator of Ability.
AB  - The purpose of this note is to focus on the finiteness of the weighted likelihood
      estimator (WLE) of ability in the context of dichotomous and polytomous item
      response theory (IRT) models. It is established that the WLE always returns
      finite ability estimates. This general result is valid for dichotomous (one-, two
      , three- and four-parameter logistic) IRT models, the class of polytomous
      difference models and divide-by-total models, independently of the number of
      items, the item parameters and the response patterns. Further implications of
      this result are outlined.

PMID- 27699561
TI  - Latent Variable Selection for Multidimensional Item Response Theory Models via
      [Formula: see text] Regularization.
AB  - We develop a latent variable selection method for multidimensional item response
      theory models. The proposed method identifies latent traits probed by items of a
      multidimensional test. Its basic strategy is to impose an [Formula: see text]
      penalty term to the log-likelihood. The computation is carried out by the
      expectation-maximization algorithm combined with the coordinate descent
      algorithm. Simulation studies show that the resulting estimator provides an
      effective way in correctly identifying the latent structures. The method is
      applied to a real dataset involving the Eysenck Personality Questionnaire.

PMID- 27699562
TI  - Discounting of Condom-Protected Sex as a Measure of High Risk for Sexually
      Transmitted Infection Among College Students.
AB  - The study examined sexual delay discounting, or the devaluation of condom
      protected sex in the face of delay, as a risk factor for sexually transmitted
      infection (STI) among college students. Participants (143 females, 117 males)
      completed the sexual delay discounting task (Johnson & Bruner, 2012) and
      questionnaires of risky sexual behavior, risk perception, and knowledge.
      Participants exhibited steeper sexual delay discounting (above and beyond general
      likelihood of having unprotected sex) when partners were viewed as more desirable
      or less likely to have a STI, with males demonstrating greater sexual delay
      discounting than females across most conditions. Importantly, greater self
      reported risky sexual behaviors were associated with higher rates of sexual delay
      discounting, but not with likelihood of using a condom in the absence of delay.
      These results provide support for considering sexual delay discounting, with
      particular emphasis on potential delays to condom use, as a risk factor for STI
      among college students.

PMID- 27699563
TI  - Randomized Comparison of Subcuticular Sutures Versus Staples for Skin Closure
      After Open Abdominal Surgery: a Multicenter Open-Label Randomized Controlled
      Trial.
AB  - BACKGROUND: The incisional surgical site infection (SSI) is an extremely common
      complication following open abdominal surgery and imposes a considerable
      treatment and cost burden. METHOD: We conducted a multicenter open-label
      randomized controlled trial at three Tokyo Metropolitan medical institutions. We
      enrolled adult patients who underwent either an elective or an emergency open
      laparotomy. Eligible patients were allocated preoperatively to undergo wound
      closure with either subcuticular sutures or staples. A central Web-based
      randomization tool was used to assign participants randomly by a permuted block
      sequence with a 1:1 allocation ratio and a block size of 4 before mass closure to
      each group. The primary endpoint was the occurrence of a superficial SSI within
      30 days after surgery in accordance with the Centers for Disease Control and
      Prevention criteria. This trial was registered with UMIN-CTR as UMIN 000004836 (
      http://www.umin.ac.jp/ctr ). RESULTS: Between September 1, 2010 and August 31,
      2015, 401 patients were enrolled and randomly assigned to either group. One
      hundred and ninety-nine patients were allocated to the subcuticular suture and
      202 patients to the staple groups (hereafter the "suture" and "staple" group,
      respectively). Three hundred and ninety-nine were eligible for the primary
      endpoint. Superficial SSIs occurred in 25 of 198 suture patients and in 27 of 201
      staple patients. Overall, the rate of superficial SSIs did not differ
      significantly between the suture and staple groups. CONCLUSION: Subcuticular
      sutures did not increase the occurrence of superficial SSIs following open
      laparotomies mainly consisting of clean-contaminated surgical procedures. The
      applicability of the wound closure material and method is likely to depend on
      individual circumstances of the patient and surgical procedure.

PMID- 27699564
TI  - Evolutionary toxicology: Meta-analysis of evolutionary events in response to
      chemical stressors.
AB  - The regulatory decision-making process regarding chemical safety is most often
      informed by evidence based on ecotoxicity tests that consider growth,
      reproduction and survival as end-points, which can be quantitatively linked to
      short-term population outcomes. Changes in these end-points resulting from
      chemical exposure can cause alterations in micro-evolutionary forces (mutation,
      drift, selection and gene flow) that control the genetic composition of
      populations. With multi-generation exposures, anthropogenic contamination can
      lead to a population with an altered genetic composition, which may respond
      differently to future stressors. These evolutionary changes are rarely discussed
      in regulatory or risk assessment frameworks, but the growing body of literature
      that documents their existence suggests that these important population-level
      impacts should be considered. In this meta-analysis we have compared existing
      contamination levels of polychlorinated biphenyls (PCBs) and polycyclic aromatic
      hydrocarbons (PAHs) that have been documented to be associated with evolutionary
      changes in resident aquatic organisms to regulatory benchmarks for these
      contaminants. The original intent of this project was to perform a meta-analysis
      on evolutionary events associated with PCB and PAH contamination. However, this
      effort was hindered by a lack of consistency in congener selection for "total"
      PCB or PAH measurements. We expanded this manuscript to include a discussion of
      methods used to determine PCB and PAH total contamination in addition to
      comparing regulatory guidelines and contamination that has caused evolutionary
      effects. Micro-evolutionary responses often lead populations onto unique and
      unpredictable trajectories. Therefore, to better understand the risk of
      population-wide alterations occurring, we need to improve comparisons of chemical
      contamination between affected locations. In this manuscript we offer several
      possibilities to unify chemical comparisons for PCBs and PAHs that would improve
      comparability among evolutionary toxicology investigations, and with regulatory
      guidelines. In addition, we identify studies documenting evolutionary change in
      the presence of PCB and PAH contamination levels below applicable regulatory
      benchmarks.

PMID- 27699565
TI  - Predictors of Elopement Exhibited by School-Aged Children With Special Health
      Care Needs: Towards the Development of a Screening Instrument for Elopement.
AB  - Elopement exhibited by school-aged children with special health care needs is a
      relatively low frequency problem behavior with the potential for severe negative
      consequences for the child and family. Using data from the Centers for Disease
      Control and Prevention (CDC) Survey of Pathways to Diagnosis and Services, our
      results represent one of the first empirical studies of variables that may be
      associated with children with special health care needs engaging in elopement.
      Using data from a nationally representative sample of children with special
      health care needs, our results revealed two variables that were statistically
      significant predictors of parent-reported elopement in the past year: (1) the
      child's chronological age, and (2) the presence of an autism spectrum disorder
      (ASD) diagnosis. We found that the likelihood of an elopement event was inversely
      related to age, but positively associated with the presence of an ASD diagnosis.
      Using parent-response items from the CDC data set, we selected a set of questions
      to screen for risk of elopement and analyzed their psychometric properties. We
      discuss the need for future research to validate this screening instrument for
      school-aged youth with special health care needs. Our study provides an initial
      psychometric analysis to support a potential screening instrument for elopement
      events among school-aged youth that needs to be validated by a longitudinal study
      of its predictive validity.

PMID- 27699566
TI  - Long-Term Outcomes of the Laparoscopic Adjustable Gastric Banding: Weight Loss
      and Removal Rate. A Single Center Experience on 301 Patients with a Minimum
      Follow-Up of 10 years.
AB  - BACKGROUND: Obesity is a chronic disease that requires procedures to enable to
      maintain good long-term results. Laparoscopic adjustable gastric banding (LAGB)
      studies with a long-term follow-up are limited and have often given conflicting
      results. We report our results in terms of banding life span and weight loss in a
      cohort of 301 patients operated on LAGB with a minimum follow-up of 10 years.
      METHODS: All patients who underwent LAGB at our university hospital between 1998
      and 2004 were included in this study. The main outcome was band survival and
      complications that led to band removal, and the secondary outcome was weight
      loss. We present raw data and data after imputation for patients lost at follow
      up. RESULTS: Most patients were women (83 %), and the mean body mass index (BMI)
      baseline was 45.2 +/- 6.7. The pars flaccida technique was performed in 50.9 % of
      the patients. All patients had at least 10 years of follow-up (range 10-16
      years). Data were available at 10 years for 79.7 % and at 15 years for 80.6 %.
      Band survival was 65.8 % at 10 years and 53.3 % at 15 years. Mean excess weight
      loss (EWL) at 5, 10, and 15 years was 41.4, 38.7, and 35.1 %, respectively.
      CONCLUSION: Despite the encouraging short-term results, LAGB shows long-term
      disappointing results in terms of weight loss and complication rates. The removal
      rate increases with time (about 3-4 % per year), and at 15 years, almost half of
      the bands had been removed.

PMID- 27699567
TI  - Health-economic evaluation of home telemonitoring for COPD in Germany: evidence
      from a large population-based cohort.
AB  - INTRODUCTION: Telemonitoring for COPD has gained much attention thanks to its
      potential of reducing morbidity and mortality, healthcare utilisation and costs.
      However, its benefit with regard to clinical and economic outcomes remains to be
      clearly demonstrated. OBJECTIVE: To analyse the effect of Europe's largest COPD
      telemonitoring pilot project on direct medical costs, health resource utilisation
      and mortality at 12 months. METHODS: We evaluated a population-based cohort using
      administrative data. Difference-in-difference estimators were calculated to
      account for time-invariant unobservable heterogeneity after removing
      dissimilarities in observable characteristics between the telemonitoring and
      control group with a reweighting algorithm. RESULTS: The analysis comprised 651
      telemonitoring participants and 7047 individuals in the standard care group. The
      mortality hazards ratio was lower in the intervention arm (HR 0.51, 95 % CI 0.30
      0.86). Telemonitoring cut total costs by 895 ? (p < 0.05) compared to COPD
      standard care, mainly driven by savings in COPD-related hospitalisations in
      (very) severe COPD patients (-1056 ?, p < 0.0001). Telemonitoring enrolees used
      healthcare (all-cause and COPD-related) less intensely with shorter hospital
      stays, fewer inpatient stays and smaller proportions of people with emergency
      department visits and hospitalisations (all p < 0.0001). Reductions in mortality,
      costs and healthcare utilisation were greater for (very) severe COPD cases.
      CONCLUSION: This is the first German study to demonstrate that telemonitoring for
      COPD is a viable strategy to reduce mortality, healthcare costs and utilisation
      at 12 months. Contrary to widespread fear, reducing the intensity of care does
      not seem to impact unfavourably on health outcomes. The evidence offers strong
      support for introducing telemonitoring as a component of case management.

PMID- 27699569
TI  - Familial Chronic Granulomatous Disease Affecting Three Siblings and Causing
      Recurrent Tuberculosis.

PMID- 27699568
TI  - The social cost of chronic kidney disease in Italy.
AB  - This study aims to estimate the mean annual social cost per patient with chronic
      kidney disease (CKD) by stages 4 and 5 pre-dialyses and cost components in Italy.
      The multicenter cross-sectional study included all adult outpatients in charge of
      the 14 main Nephrology Centers of Tuscany Region during 7 weeks from 2012 to
      2013. Direct medical costs have been estimated using tariffs for laboratory
      tests, diagnostic exams, visits, hospitalization and prices for drugs. Non
      medical costs included expenses of low-protein special foods, travel, and formal
      and informal care. Patients' and caregivers' losses of productivity have been
      estimated as indirect costs using the human capital approach. Costs have been
      expressed in Euros (2016). Totals of 279 patients in stage 4 and 205 patients in
      stage 5 have been enrolled. The estimated mean annual social cost of a patient
      with CKD were ?7422 (+/-?6255) for stage 4 and ?8971 (+/-?6503) for stage 5 (p <
      0.05). Direct medical costs were higher in stage 5 as compared to stage 4; direct
      non-medical costs and indirect costs accounted, respectively, for 41 and 5 % of
      the total social cost of CKD stage 4 and for 33 and 9 % of CKD stage 5. In Italy,
      the overall annual social cost of CKD was ?1,809,552,398 representing 0.11 % of
      the Gross Domestic Product. Direct non-medical costs and indirect costs were
      weighted on the social cost of CKD almost as much as the direct medical cost.
      Patients, their families and the productivity system sustain the burden of the
      disease almost as much as the healthcare system.

PMID- 27699570
TI  - The Importance of Measuring IL10 Levels in Patients with Suspected IL10/IL10R
      Defects.

PMID- 27699571
TI  - Clinical, Immunological, and Molecular Findings of Patients with p47phox Defect
      Chronic Granulomatous Disease (CGD) in Indian Families.
AB  - Chronic granulomatous disease (CGD) is a group of inherited disorder of
      phagocytes, resulting from mutations in the components of the NADPH oxidase
      complex. Reduced or absent oxygen radical synthesis seen in these patients leads
      to impaired killing of intracellular bacteria and fungi. CGD clinically presents
      with recurrent and life-threatening infections as well as granulomatous
      inflammatory responses. p47phox encoded by the NCF1 gene is the most common
      autosomal recessive form of CGD which is often clinically milder. Here, we are
      presenting the data on clinical and immunological findings in 21 Indian patients
      with Del GT mutation in the NCF1 gene. Diagnosis of these patients was based on
      detailed clinical evaluation, measurement of respiratory burst activity by nitro
      blue tetrazolium and dihydrorhodamine-1,2,3 assay, expression of p47phox by flow
      cytometry, and molecular confirmation by GeneScan method. Seventeen male and four
      female patients with median age of onset of 1 year ranging from 1.5 months to 6
      years were included in the study. Sixty-two percent (13 out of 21) of patients
      belonged to a consanguineous marriage with only one family having a history of a
      previous sibling death. Significant variability in clinical presentation was
      observed in spite of identical genetic defect ranging from asymptomatic to very
      severe presentation leading to early death or requiring transplantation. However,
      none of these patients showed difference in immunological parameters to account
      for this variability. Thus, this study highlights the phenotypic heterogeneity
      seen in these patients with Del GT mutation in the NCF1 gene and its implication
      in management of these patients.

PMID- 27699573
TI  - Direct communication between osteocytes and acid-etched titanium implants with a
      sub-micron topography.
AB  - The osteocyte network, through the numerous dendritic processes of osteocytes, is
      responsible for sensing mechanical loading and orchestrates adaptive bone
      remodelling by communicating with both the osteoclasts and the osteoblasts. The
      osteocyte network in the vicinity of implant surfaces provides insight into the
      bone healing process around metallic implants. Here, we investigate whether
      osteocytes are able to make an intimate contact with topologically modified, but
      micrometre smooth (S a < 0.5 um) implant surfaces, and if sub-micron topography
      alters the composition of the interfacial tissue. Screw shaped, commercially pure
      (cp-Ti) titanium implants with (i) machined (S a = ~0.2 um), and (ii) two-step
      acid-etched (HF/HNO3 and H2SO4/HCl; S a = ~0.5 um) surfaces were inserted in
      Sprague Dawley rat tibia and followed for 28 days. Both surfaces showed similar
      bone area, while the bone-implant contact was 73 % higher for the acid-etched
      surface. By resin cast etching, osteocytes were observed to maintain a direct
      intimate contact with the acid-etched surface. Although well mineralised, the
      interfacial tissue showed lower Ca/P and apatite-to-collagen ratios at the acid
      etched surface, while mineral crystallinity and the carbonate-to-phosphate ratios
      were comparable for both implant surfaces. The interfacial tissue composition may
      therefore vary with changes in implant surface topography, independently of the
      amount of bone formed. Implant surfaces that influence bone to have higher
      amounts of organic matrix without affecting the crystallinity or the carbonate
      content of the mineral phase presumably result in a more resilient interfacial
      tissue, better able to resist crack development during functional loading than
      densely mineralised bone.

PMID- 27699572
TI  - Primary Immunodeficiency Diseases in Oman: 10-Year Experience in a Tertiary Care
      Hospital.
AB  - PURPOSE: Primary immunodeficiency (PID) diseases are rare, complex medical
      disorders that often are overlooked in clinical settings. There are emerging
      reports of PID from Middle Eastern populations. This study describes the features
      of PID patients in a tertiary care setting in Oman and compares them with
      regional and worldwide reports. METHOD: Sultan Qaboos University Hospital (SQUH)
      is an academic tertiary care-level hospital for specialized healthcare, including
      PID patients. At the time of diagnosis, patients' sociodemographics, clinical
      features, laboratory investigations, and management were entered in electronic
      form. This study included patients seen between August 2005 and July 2015.
      RESULTS: One hundred forty patients were registered with a minimum estimated
      population prevalence of 7.0/100,000. The male/female ratio was 1.6:1, the median
      age of onset of symptoms was 8 months, and diagnosis was 21 months with a delay
      of 13 months. Family history was positive in 44 %, consanguinity was present in
      76 %, death of a previous sibling was present in 36 %, and there was an overall
      mortality in 18 %, with an 85 % probability of survival 10 years following
      diagnosis. The most common type of immunodeficiency was phagocytic disorders
      (35.0 %), followed by predominantly antibody disorders (20.7 %), combined
      immunodeficiency (17.8 %), other well-defined PID syndromes (15.0 %), immune
      dysregulation syndromes (3.5 %), complement deficiencies (3.5 %), and
      unclassified immunodeficiency (4.2 %). The commonest presenting infection was
      pneumonia (47.1 %). CONCLUSION: PID is not a rare condition in Oman. The
      prevalence is in concordance with reports from the region but higher than in
      Western populations. The findings of the current study would help to improve the
      awareness and management of, and policy making for PID.

PMID- 27699574
TI  - Effect of bioactive dental adhesive on periodontal and endodontic pathogens.
AB  - The objectives of this study were to: (1) develop a new bioactive dental bonding
      agent with nanoparticles of amorphous calcium phosphate and
      dimethylaminohexadecyl methacrylate for tooth root caries restorations and
      endodontic applications, and (2) investigate biofilm inhibition by the bioactive
      bonding agent against eight species of periodontal and endodontic pathogens for
      the first time. Bonding agent was formulated with 5 % of dimethylaminohexadecyl
      methacrylate. Nanoparticles of amorphous calcium phosphate at 30 wt% was mixed
      into adhesive. Eight species of biofilms were grown on resins: Porphyromonas
      gingivalis, Prevotella intermedia, Prevotella nigrescens, Aggregatibacter
      actinomycetemcomitans, Fusobacterium nucleatum, Parvimonas micra, Enterococcus
      faecalis, Enterococcus faecium. Colony-forming units, live/dead assay, biomass,
      metabolic activity and polysaccharide of biofilms were determined. The results
      showed that adding dimethylaminohexadecyl methacrylate and nanoparticles of
      amorphous calcium phosphate into bonding agent did not decrease dentin bond
      strength (P > 0.1). Adding dimethylaminohexadecyl methacrylate reduced the colony
      forming units of all eight species of biofilms by nearly three orders of
      magnitude. The killing efficacy of dimethylaminohexadecyl methacrylate resin was:
      P. gingivalis > A. actinomycetemcomitans > P. intermedia > P. nigrescens > F.
      nucleatum > P. micra > E. faecalis > E. faecium. Dimethylaminohexadecyl
      methacrylate resin had much less biomass, metabolic activity and polysaccharide
      of biofilms than those without dimethylaminohexadecyl methacrylate (P < 0.05). In
      conclusion, a novel dental adhesive was developed for root caries and endodontic
      applications, showing potent inhibition of biofilms of eight species of
      periodontal and endodontic pathogens, and reducing colony-forming units by three
      orders of magnitude. The bioactive adhesive is promising for tooth root
      restorations to provide subgingival margins with anti-periodontal pathogen
      capabilities, and for endodontic sealer applications to combat endodontic
      biofilms.

PMID- 27699575
TI  - Analysis of thrombosis and bleeding complications in patients with polycythemia
      vera: a Turkish retrospective study.
AB  - The aims of this study are to determine the incidence and risk factors of
      thrombosis and bleeding in polycythemia vera (PV) patients and to research the
      effects of these risk factors on survival. The medical records of 155 PV patients
      were analyzed retrospectively. Patients were divided into groups according to
      whether or not thrombosis had developed in follow-up, and according to whether or
      not bleeding had occurred during follow-up. The mean age at diagnosis was 53
      years, and the mean follow-up period was 66 months. The percentage of cases in
      which thrombosis events had occurred before diagnosis and during follow-up were
      26 and 28 %, respectively. Comparisons of disease duration and average thrombosis
      risk score between groups with or without thrombosis drew statistically
      significant results. A patient's history of thrombosis and thrombocytosis at
      first visit was found to have a significant effect on thrombosis recurrence. The
      major bleeding rate was 8 %. Post-PV myelofibrosis was an independent risk factor
      for bleeding. The major cause of death among the patients in this study was
      primary thrombosis. The most important causes of mortality among PV patients are
      thrombosis, and the most prominent risk factors for thrombosis development are
      disease duration and high thrombosis risk scores. Thrombocytosis in patients with
      a history of thrombosis may cause thrombosis recurrence during the follow-up
      period.

PMID- 27699577
TI  - Relationship between power Doppler grade and the pathological blood vessel
      features in long-standing rheumatoid arthritis.

PMID- 27699576
TI  - Cutaneous localization in multiple myeloma in the context of bortezomib-based
      treatment: how do myeloma cells escape from the bone marrow to the skin?
AB  - The skin is a possible site of extramedullary localization in multiple myeloma
      (MM) patients; however, the mechanisms involved in this process are poorly
      understood. We describe the case of a refractory MM patient who developed a
      cutaneous localization under bortezomib treatment and we further expanded
      observations in other eight MM patients. We focused on the expression of genes
      involved in plasma cell skin homing, including CCR10, which was highly expressed.
      Moreover, we observed a lack of CXCR4 surface expression and the down-regulation
      of ICAM1/CD54 throughout the progression of the disease, suggesting a possible
      mechanism driving the escape of MM cells from the bone marrow into the skin.

PMID- 27699578
TI  - Re-initiation of biologics after the development of tuberculosis under anti-TNF
      therapy.
AB  - The use of anti-TNF agents is associated with an increased risk of tuberculosis
      (TB) and anti-TNF agents are stopped when active TB develops. However,
      discontinuation of treatment can result in flare of the underlying disease. The
      charts of 22 patients who developed active TB among a cohort of 2754 patients
      using anti-TNF agents between 2001 and 2013 were reviewed retrospectively.
      Patients restarting biologics during further follow-up were identified. One
      patient with miliary TB died within 1 month. A biologic agent was restarted in 16
      of the remaining 21 patients (76 %). The most frequently re-initiated biologic
      agent was etanercept (n = 6) followed by rituximab (n = 5) and interferon-alpha
      (n = 3). Biologic treatment was re-initiated during anti-TB treatment in four
      patients and after completing TB treatment in 12 patients. The median follow-up
      after restarting biologics was 53 (IQR: 40-75) months. TB re-occurred in one
      patient with Behcet's syndrome, who initially received etanercept due to severe
      sight-threatening uveitis at the third month of anti-TB treatment followed by
      canakinumab 15 months later along with methotrexate, cyclosporine and
      corticosteroids. After a second course of 9 months TB therapy this patient is
      currently stable on interferon-alpha for 33 months. Restarting of anti-TNF agents
      and other biologic agents, even during TB treatment, seems to be possible among
      patients who had previously developed TB under anti-TNF treatment. However, the
      risk of re-development of TB infection mandates careful follow-up.

PMID- 27699579
TI  - Postoperative dysglycemia in elective non-diabetic surgical patients: a
      prospective observational study.
AB  - PURPOSE: Elevated glycosylated hemoglobin (HbA1c) is often found in surgical
      patients with no history of diabetes. The purpose of this prospective
      observational study was to determine if elevated preoperative HbA1c is associated
      with postoperative hyperglycemia in non-diabetic surgical patients and to
      identify predictors of elevated HbA1c. METHODS: This study included 257 non
      diabetic adults scheduled for inpatient surgery. Preoperatively, capillary blood
      glucose (CBG) and HbA1c were measured and patients completed the Canadian
      Diabetes Risk Questionnaire (CANRISK). Capillary blood glucose was measured for
      two days or until hospital discharge at the following time points:
      postoperatively, before all meals, and at 22:00 hr. The mean CBG and incidence of
      hyperglycemia were compared between HbA1c levels: Group I < 6.0%, Group II 6.0
      6.4%, and Group III >= 6.5%. RESULTS: The mean postoperative glucose levels at
      all time points were significantly higher in Group III compared with Groups I and
      II (P < 0.01). At least one episode of hyperglycemia (CBG >= 10.0 mMol.L-1)
      occurred in 61% (11/18) of patients in Group III vs 11% (23/209) of patients in
      Group I (relative risk, 5.55; 95% confidence interval [CI], 3.26 to 9.47; P <
      0.001). Elevated glycosylated hemoglobin >= 6.0% was found in 31% (33/107) of
      those with a high CANRISK score. The best predictors of postoperative
      hyperglycemia were preoperative CBG > 6.9 mMol.L-1 [diagnostic odds ratio (OR)
      (reference < 6.0 mMol.L-1), 4.16; 95% CI, 1.57 to 10.98; P = 0.004], HbA1c >=
      6.0% [OR (reference < 6.0%), 3.00; 95% CI, 1.39 to 6.49; P = 0.005], and HbA1c >=
      6.5% [OR (reference < 6.5%), 13.45; 95% CI, 4.78 to 37.84; P <0.001].
      CONCLUSIONS: Elevated HbA1c is associated with higher mean postoperative glucose
      levels in patients with no diabetic history. The CANRISK score is a strong
      predictor of elevated HbA1c, while CBG and HbA1c are both predictors of
      postoperative hyperglycemia.

PMID- 27699581
TI  - Mental and Physical Health among Homeless Sexual and Gender Minorities in a Major
      Urban US City.
AB  - Sexual and gender minorities have been shown to have greater rates of mental
      health, substance use disorders, and specific types of health problems compared
      to heterosexuals. Among the homeless population in several US urban areas, sexual
      and gender minorities are overrepresented but few studies have examined the
      mental and physical health status of homeless sexual and gender minorities, with
      studies on homeless gender minorities being particularly hard to find. Using
      survey data obtained from the city and county of San Francisco (2015 Homeless
      Survey), this study examined differences in causes of homelessness, physical and
      mental health problems, and domestic violence among homeless sexual and gender
      minorities and their heterosexual and cisgender (i.e., non-transgender)
      counterparts, respectively. Lesbians and bisexual women, and gay and bisexual men
      did not differ from their cisgender heterosexual counterparts. Cisgender men who
      identified as queer or "other" in response to sexual orientation questions had
      higher rates of psychiatric problems and posttraumatic stress disorder, while
      cisgender women who identified as queer or "other" had higher rates of
      psychiatric problems and drug and alcohol use. Transgender men who were homeless
      were found to be particularly at risk for physical health problems, mental health
      problems, and domestic violence or abuse. Transgender women were more likely to
      report posttraumatic stress disorder. This study suggests that transgender men
      and cisgender sexual minority men and women who identify as queer or "other" are
      groups among the homeless that may benefit from increased outreach and services.

PMID- 27699582
TI  - Peroxisome proliferator-activated receptor gamma co-activator 1 gene Gly482Ser
      polymorphism is associated with the response of low-density lipoprotein
      cholesterol concentrations to exercise training in elderly Japanese.
AB  - Muscle peroxisome proliferator-activated receptor gamma co-activator 1 (PGC
      1)alpha gene expression is influenced by the Gly482Ser gene polymorphism, which
      is a candidate genetic risk factor for diabetes mellitus and obesity. This study
      investigated the effects of PGC-1 gene Gly482Ser polymorphisms on alterations in
      glucose and lipid metabolism induced by exercise training. A 12-week intervention
      study was performed for 119 participants who were more than 65 years of age and
      completed exercise training at lactate threshold intensity. Total cholesterol and
      low-density lipoprotein cholesterol were significantly reduced in Gly/Gly but not
      in Gly/Ser and Ser/Ser participants after exercise. The Gly/Gly genotype of the
      PGC-1 gene Gly482Ser polymorphism influences the effects of moderate-intensity
      exercise training on low-density lipoprotein cholesterol and total cholesterol
      concentrations in older people.

PMID- 27699580
TI  - Inflammasomes and its importance in viral infections.
AB  - A complex interplay between pathogen and host determines the immune response
      during viral infection. A set of cytosolic sensors are expressed by immune cells
      to detect viral infection. NOD-like receptors (NLRs) comprise a large family of
      intracellular pattern recognition receptors. Members of the NLR family assemble
      into large multiprotein complexes, termed inflammasomes, which induce downstream
      immune responses to specific pathogens, environmental stimuli, and host cell
      damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3
      or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated
      speck-like protein containing caspase recruitment domain), and the effector
      protein procaspase-1. The inflammasome operates as a platform for caspase-1
      activation, resulting in caspase-1-dependent proteolytic maturation and secretion
      of interleukin (IL)-1beta and IL-18. This, in turn, activates the expression of
      other immune genes and facilitates lymphocyte recruitment to the site of primary
      infection, thereby controlling invading pathogens. Moreover, inflammasomes
      counter viral replication and remove infected immune cells through an
      inflammatory cell death, program termed as pyroptosis. As a countermeasure, viral
      pathogens have evolved virulence factors to antagonise inflammasome pathways. In
      this review, we discuss the role of inflammasomes in sensing viral infection as
      well as the evasion strategies that viruses have developed to evade inflammasome
      dependent immune responses. This information summarises our understanding of host
      defence mechanisms against viruses and highlights research areas that can provide
      new approaches to interfere in the pathogenesis of viral diseases.

PMID- 27699583
TI  - Prostaglandins mediate zymosan-induced sickness behavior in mice.
AB  - Previous studies have demonstrated that zymosan, a cell wall component of the
      yeast Saccharomyces cerevisiae, induces inflammation in experimental models.
      However, few studies have evaluated the potential of zymosan to induce sickness
      behavior, a central motivational state that allows an organism to cope with
      infection. To determine whether zymosan administration results in sickness
      behavior, mice were submitted to the forced swim (FST) and open field (OFT) tests
      2, 6, and 24 h after treatment with zymosan (1, 10, or 100 mg/kg). Additionally,
      to evaluate the possible relationship between zymosan-induced sickness behavior
      and prostaglandin synthesis, mice were pretreated with the cyclooxygenase
      inhibitors indomethacin (10 mg/kg) and nimesulide (5 mg/kg) and the
      glucocorticoid drug dexamethasone (1 mg/kg). Zymosan induced time-dependent
      decreases in locomotor activity in the OFT, and an increase in immobility in the
      FST, and increased plasma levels of corticosterone at 2 h. Pretreatment with
      indomethacin, nimesulide, or dexamethasone blocked zymosan-induced behavioral
      changes in both the FST and OFT at 2 h post administration. These findings
      confirm previous observations that zymosan induces sickness behavior.
      Furthermore, our results provide new evidence that prostaglandin synthesis is
      necessary for this effect, as anti-inflammatory drugs that inhibit prostaglandin
      synthesis attenuated zymosan-induced behavioral changes.

PMID- 27699584
TI  - Ceritinib: a Review in ALK-Positive Advanced NSCLC.
AB  - Ceritinib (ZykadiaTM) is an oral, selective inhibitor of the anaplastic lymphoma
      kinase (ALK), a receptor tyrosine kinase which, after genetic rearrangement, acts
      as an oncogenic driver in a proportion of non-small cell lung cancers (NSCLCs).
      The drug is approved in several countries worldwide for the treatment of patients
      with ALK-positive, advanced NSCLC who have previously received the first
      generation ALK inhibitor crizotinib (indication details may vary by country).
      Approval was based on its clinical benefit in this setting in the phase I and II
      trials known as ASCEND-1 and -2. Across these noncomparative studies, 36-56 % of
      patients achieved a response with ceritinib (at the recommended dosage of 750 mg
      once daily) and the responses were durable, lasting up to a median of 10 months.
      Patients survived free from progression for a median of up to 7 months and had a
      median overall survival of up to 17 months. Moreover, efficacy outcomes in
      patients with brain metastases were generally consistent with those of the
      overall study populations. Ceritinib has an acceptable tolerability profile, with
      gastrointestinal issues, fatigue and liver test abnormalities being the most
      common adverse reactions. Thus, ceritinib is a valuable treatment option for
      patients with ALK-positive advanced NSCLC who have already received crizotinib
      therapy.

PMID- 27699585
TI  - Click inspired synthesis of triazole-linked vanillin glycoconjugates.
AB  - The 1,3-dipolar cycloaddition of deoxy-azido sugars 1 with alkyne derivatives of
      p-vanillin, 3-methoxy-4-(prop-2-ynyloxy)benzaldehyde (2) and 2-methoxy-1-(prop-2
      ynyloxy)-4-((prop-2-ynyloxy)methyl)benzene) (4) to afford regioselective triazole
      linked vanillinglycoconjugates 5 and 6 was investigated in the presence of
      CuI/DIPEA in dichloromethane. All the developed glycoconjugates were
      characterized on the basis of IR, NMR, and MS. Graphical abstract Triazolyl
      vanillin glycoconjugates via click chemistry.

PMID- 27699586
TI  - Non-invasive Vagus Nerve Stimulation (nVNS) as mini-prophylaxis for
      menstrual/menstrually related migraine: an open-label study.
AB  - BACKGROUND: Menstrual migraine and menstrually related migraine attacks are
      typically longer, more disabling, and less responsive to medications than non
      menstrual attacks. The aim of this study was to evaluate the efficacy, safety,
      and tolerability of non-invasive vagus nerve stimulation for the prophylactic
      treatment of menstrual migraine/menstrually related migraine. METHODS: Fifty-six
      enrolled subjects (menstrual migraine, 9 %; menstrually related migraine, 91 %),
      33 (59 %) of whom were receiving other prophylactic therapies, entered a 12-week
      baseline period. Fifty-one subjects subsequently entered a 12-week treatment
      period to receive open-label prophylactic non-invasive vagus nerve stimulation
      adjunctively (31/51; 61 %) or as monotherapy (20/51; 39 %) on day -3 before
      estimated onset of menses through day +3 after the end of menses. RESULTS: The
      number of menstrual migraine/menstrually related migraine days per month was
      significantly reduced from baseline (mean +/- standard error, 7.2 +/- 0.7 days)
      to the end of treatment (mean +/- standard error, 4.7 +/- 0.5 days; P < 0.001)
      (primary end point). Of all subjects, 39 % (95 % confidence interval: 26 %, 54 %)
      (20/51) had a >= 50 % reduction (secondary end point). For the other secondary
      end points, clinically meaningful reductions in analgesic use (mean change +/-
      standard error, -3.3 +/- 0.6 times per month; P < 0.001), 6-item Headache Impact
      Test score (mean change +/- standard error, -3.1 +/- 0.7; P < 0.001), and
      Migraine Disability Assessment score (mean change +/- standard error, -11.9 +/-
      3.4; P < 0.001) were observed, along with a modest reduction in pain intensity
      (mean change +/- standard error, -0.5 +/- 0.2; P = 0.002). There were no
      safety/tolerability concerns. CONCLUSIONS: These findings suggest that non
      invasive vagus nerve stimulation is an effective treatment that reduces the
      number of menstrual migraine/menstrually related migraine days and analgesic use
      without safety/tolerability concerns in subjects with menstrual
      migraine/menstrually related migraine. Randomised controlled studies are
      warranted.

PMID- 27699587
TI  - Effects of Antihypertensive Therapy on Blood Pressure Variability.
AB  - PURPOSE OF REVIEW: The study aims to summarize the effect of antihypertensive
      therapy on various types of BP variability in hypertensives. RECENT FINDINGS:
      Visit-to-visit, day-by-day, and ambulatory BPV are markers of target organ damage
      and cardiovascular prognosis, as was shown in the LIFE study, which showed that
      visit-to-visit variability in BP predicted cardiovascular events in treated
      hypertensive patients with left ventricular hypertrophy. Long-acting calcium
      channel blockers (CCBs) may be a preferable treatment in reducing BPV measures.
      Non-adherence to antihypertensive medication is also a very important component
      of increased BPV, and improving the adherence is also a key for the favorable
      prognosis. BPV cannot be a target of antihypertensive treatments because of the
      lack of definitive evidence. However, in high-risk patients, those with
      cardiovascular or cerebrovascular diseases, the clinical significance should be
      considered in individual basis. Especially, reduction of BPV would be an
      important strategy for these patients.

PMID- 27699589
TI  - Cinobufotalin impedes Sw.71 cytotrophoblast cell line function via cell cycle
      arrest and apoptotic signaling.
AB  - Preeclampsia (preE) is a hypertensive disorder of pregnancy. Cardiotonic steroids
      (CTS) are endogenous inhibitors of Na+/K+ ATPase, and at least one CTS,
      marinobufagenin (MBG), is elevated in a rat model of preE prior to the
      development of the syndrome. MBG and ouabain impair cytotrophoblast (CTB) cell
      function, which is critical for placental development. We evaluated the effect of
      a CTS, cinobufotalin (CINO), on CTB cell function in vitro. CINO at >=1 nM
      inhibited CTB cell proliferation, migration, and invasion (p < 0.05), but had no
      effect on cell viability. There was a higher (p < 0.05) percentage of G0/G1 phase
      cells in groups treated with CINO at >=1 nM. CINO caused an increase in stress
      signaling p38 MAPK and a positive annexin-V staining in CTB cells, indicating the
      activation of apoptotic signaling. However, the CINO-induced apoptotic signaling
      was prevented by p38 inhibition. These data demonstrate that CINO impairs CTB
      cell function via cell cycle arrest and apoptotic signaling.

PMID- 27699591
TI  - Erratum to: Characterization of graphomotor functions in individuals with
      Parkinson's disease and essential tremor.

PMID- 27699588
TI  - The protein-interaction network with functional roles in tumorigenesis,
      neurodegeneration, and aging.
AB  - The present review summarizes the knowledge about a protein-interaction network,
      which includes proteins with significant functions in the mechanisms of aging and
      age-related diseases. All the detected interacting proteins TPPII, p53, MYBBP1A,
      CDK2 and SIRT7, SIRT6, and CD147 are suitable for the development of antitumor
      therapeutics and treatments for diseases of aging. TPPII and SIRT6 directly
      affect glucose metabolism which drive malignant growth. In addition, SIRT6
      activators are attractive candidates for Alzheimer's disease (AD) due to the
      protection effect of SIRT6 overexpression from DNA damage. TPPII activity
      exhibits a decreasing effect on mTOR signaling, and its requirement for the
      degradation of Abeta peptides in the human fibroblasts suggests that it has dual
      functions in tumorigenesis and AD-related pathology. Likewise, the direct
      promotion of the invasiveness of breast epithelial cells and the contribution to
      the Abeta degradation by stimulating the matrix metalloproteinases production
      suggest a double functional role for CD147. An association of the partial portion
      of cellular CD147 to gamma-secretase further supports the functional relation to
      AD pathology. The animal and cellular models with downregulated or knockout
      TPPII, p53, SIRT6, SIRT7, and MYBBP1A expression levels illustrate similar
      functions of the interacting proteins. They demonstrate similar effects on the
      length of life span, premature aging, and lipid metabolism. The presented protein
      interaction network is relevant to the discoveries of the mechanisms of
      tumorigenesis, aging, and neurodegeneration.

PMID- 27699590
TI  - High-fructose diet is as detrimental as high-fat diet in the induction of insulin
      resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER)
      stress.
AB  - In the context of high human consumption of fructose diets, there is an
      imperative need to understand how dietary fructose intake influence cellular and
      molecular mechanisms and thereby affect beta-cell dysfunction and insulin
      resistance. While evidence exists for a relationship between high-fat-induced
      insulin resistance and metabolic disorders, there is lack of studies in relation
      to high-fructose diet. Therefore, we attempted to study the effect of different
      diets viz., high-fat diet (HFD), high-fructose diet (HFS), and a combination (HFS
      + HFD) diet on glucose homeostasis and insulin sensitivity in male Wistar rats
      compared to control animals fed with normal pellet diet. Investigations include
      oral glucose tolerance test, insulin tolerance test, histopathology by H&E and
      Masson's trichrome staining, mRNA expression by real-time PCR, protein expression
      by Western blot, and caspase-3 activity by colorimetry. Rats subjected to high
      fat/fructose diets became glucose intolerant, insulin-resistant, and
      dyslipidemic. Compared to control animals, rats subjected to different
      combination of fat/fructose diets showed increased mRNA and protein expression of
      a battery of ER stress markers both in pancreas and liver. Transcription factors
      of beta-cell function (INSIG1, SREBP1c and PDX1) as well as hepatic
      gluconeogenesis (FOXO1 and PEPCK) were adversely affected in diet-induced insulin
      resistant rats. The convergence of chronic ER stress towards apoptosis in
      pancreas/liver was also indicated by increased levels of CHOP mRNA & increased
      activity of both JNK and Caspase-3 in rats subjected to high-fat/fructose diets.
      Our study exposes the experimental support in that high-fructose diet is equally
      detrimental in causing metabolic disorders.

PMID- 27699592
TI  - Revisiting Rossion and Pourtois with new ratings for automated complexity,
      familiarity, beauty, and encounter.
AB  - Differences between norm ratings collected when participants are asked to
      consider more than one picture characteristic are contrasted with the traditional
      methodological approaches of collecting ratings separately for image constructs.
      We present data that suggest that reporting normative data, based on
      methodological procedures that ask participants to consider multiple image
      constructs simultaneously, could potentially confounded norm data. We provide
      data for two new image constructs, beauty and the extent to which participants
      encountered the stimuli in their everyday lives. Analysis of this data suggests
      that familiarity and encounter are tapping different image constructs. The extent
      to which an observer encounters an object predicts human judgments of visual
      complexity. Encountering an image was also found to be an important predictor of
      beauty, but familiarity with that image was not. Taken together, these results
      suggest that continuing to collect complexity measures from human judgments is a
      pointless exercise. Automated measures are more reliable and valid measures,
      which are demonstrated here as predicting human preferences.

PMID- 27699593
TI  - Biodegradable starch derivatives with tunable charge density-synthesis,
      characterization, and transfection efficiency.
AB  - Regioselective oxidation of water-soluble starch and conversion with alkyl
      diamines resulted in defined cationic starch derivatives. Those were assessed in
      their potential for polyplex formation, biocompatibility, and transfection
      efficacy. The new polymers have the advantage of being biodegradable, being not
      cytotoxic at rather high concentrations (LC50 > 400 MUg/ml) for C2 substitution,
      and reach transfection efficiencies comparable to commercial transfection
      reagents. The polymer with the highest transfection efficacy is a C12 substituted
      polymer (degree of substitution = 30 %) at N/P 3. The LC50 value of that highly
      modified polymer is still one order of magnitude lower than that of PEI 25 kDa.

PMID- 27699595
TI  - Alcohol Use and Food Insecurity Among People Living with HIV in Mbarara, Uganda
      and St. Petersburg, Russia.
AB  - Food insecurity (FI) is a documented problem associated with adverse health
      outcomes among HIV-infected populations. Little is known about the relationship
      between alcohol use and FI. We assessed whether heavy alcohol use was associated
      with FI among HIV-infected, antiretroviral therapy (ART)-naive cohorts in Uganda
      and Russia. Inverse probability of treatment weighted logistic regression models
      were used to evaluate the association using cross-sectional baseline data. FI was
      experienced by half of the Russia cohort (52 %) and by a large majority of the
      Uganda cohort (84 %). We did not detect an association between heavy alcohol use
      and FI in either cohort (Russia: AOR = 0.80, 95 % CI 0.46, 1.40; Uganda: AOR =
      1.00, 95 % CI 0.57, 1.74) or based on the overall combined estimate (AOR = 0.89,
      95 % CI 0.60, 1.33). Future studies should explore the determinants of FI in HIV
      infected populations to inform strategies for its mitigation.

PMID- 27699596
TI  - The Interaction of Risk Network Structures and Virus Natural History in the Non
      spreading of HIV Among People Who Inject Drugs in the Early Stages of the
      Epidemic.
AB  - This article explores how social network dynamics may have reduced the spread of
      HIV-1 infection among people who inject drugs during the early years of the
      epidemic. Stochastic, discrete event, agent-based simulations are used to test
      whether a "firewall effect" can arise out of self-organizing processes at the
      actor level, and whether such an effect can account for stable HIV prevalence
      rates below population saturation. Repeated simulation experiments show that, in
      the presence of recurring, acute, and highly infectious outbreaks, micro-network
      structures combine with the HIV virus's natural history to reduce the spread of
      the disease. These results indicate that network factors likely played a
      significant role in the prevention of HIV infection within injection risk
      networks during periods of peak prevalence. They also suggest that social forces
      that disturb network connections may diminish the natural firewall effect and
      result in higher rates of HIV.

PMID- 27699594
TI  - Objective Measurement of Inaccurate Condom Use Reporting Among Women Using Depot
      Medroxyprogesterone Acetate for Contraception.
AB  - Observational analyses have suggested that women using the injectable
      contraceptive depot medroxyprogesterone acetate (DMPA) may have heightened risk
      of acquiring HIV. However, those analyses were potentially confounded by sexual
      behavior, with possible differential condom use and reporting by women using DMPA
      versus no contraception. In a cross-sectional study, we measured the presence of
      a biomarker of recent condomless sex (Y chromosomal [Yc] DNA) in vaginal swabs
      from HIV-uninfected African women who had an HIV-infected partner and reported
      100 % condom use. Half of the samples tested were from women reporting DMPA and
      half were from women using no contraception. Among 428 specimens tested (213 from
      DMPA users and 215 from women using no contraception), 32.0 % had Yc DNA
      detected, with a mean of 193 copies/10,000 human cells (range 0.1-8201). The
      frequency of detection did not differ by contraceptive use: 34.2 % of DMPA users
      versus 29.8 % of women using no contraception, adjusted odds ratio 1.3 (95 %
      confidence interval 0.9-2.0). These results suggest that inaccurate reporting of
      condom use by DMPA users may not account for the heightened risk of HIV
      acquisition among DMPA users in some observational studies.

PMID- 27699597
TI  - Food Security Status is Related to Mental Health Quality of Life Among Persons
      Living with HIV.
AB  - This study evaluated the association between health related quality of life and
      food security among persons living with HIV (PLHIV). We studied 167 PLHIV who
      completed questionnaires assessing food security, disease symptomatology, and
      several domains of the SF-36 health related quality of life survey. HIV disease
      state was assessed from medical records. Associations between independent and
      outcome variables were determined through linear regression models. Compared to
      food security, very low food security was significantly associated with lower
      mental component summary scores, [average difference -4.98 (95 % CI -9.85, 
      0.10)]; mental health, [average difference -5.44 (95 % CI -10.08, -0.81)]; and
      general health, [average difference -5.13 (95 % CI -9.65, -0.65)] after adjusting
      for covariates. About a fourth of participants experienced severe food
      insecurity, which negatively influenced their mental health and general
      wellbeing. The inclusion of resources for food assistance in HIV treatment
      programs may help ameliorate mental health challenges faced by PLHIV.

PMID- 27699598
TI  - Ischemic Post-Conditioning Induces Post-Stroke Neuroprotection via Hsp70-Mediated
      Proteasome Inhibition and Facilitates Neural Progenitor Cell Transplantation.
AB  - In view of the failure of pharmacological therapies, alternative strategies
      promoting post-stroke brain repair are needed. Post-conditioning is a potentially
      promising therapeutic strategy, which induces acute neuroprotection against
      ischemic injury. To elucidate longer lasting actions of ischemic post
      conditioning, mice were exposed to a 60-min stroke and post-conditioning by an
      additional 10-min stroke that was induced 10 min after reperfusion onset. Animals
      were sacrificed 24 h or 28 days post-stroke. Post-conditioning reduced infarct
      volume and neurological deficits 24 h post-stroke, enhancing blood-brain barrier
      integrity, reducing brain leukocyte infiltration, and reducing oxidative stress.
      On the molecular level, post-conditioning yielded increased Hsp70 expression,
      whereas nuclear factor (NF)-kappaB and proteasome activities were decreased.
      Reduced infarct volume and proteasome inhibition were reversed by Hsp70
      knockdown, suggesting a critical role of the Hsp70 proteasome pathway in ischemic
      post-conditioning. The survival-promoting effects of ischemic post-conditioning,
      however, were not sustainable as neuroprotection and neurological recovery were
      lost 28 days post-stroke. Although angioneurogenesis was not increased by post
      conditioning, the favorable extracellular milieu facilitated intracerebral
      transplantation of neural progenitor cells 6 h post-stroke, resulting in
      persisted neuroprotection and neurological recovery. Thus, post-conditioning
      might support brain repair processes, but in view of its transient,
      neuroprotection is unlikely useful as stroke therapy in its current form.

PMID- 27699600
TI  - The Motor KIF5C Links the Requirements of Stable Microtubules and IGF-1 Receptor
      Membrane Insertion for Neuronal Polarization.
AB  - Three early signals of asymmetry have been described to occur in a single neurite
      of neurons at stage 2 of differentiation (before polarization) and shown to be
      essential for neuronal polarization: (i) accumulation of stable microtubules,
      (ii) enrichment of the plasma membrane with activatable IGF-1r, and (iii)
      polarized transport of the microtubular motor KIF5C. Here, we studied the
      possible relationship between these three phenomena. Our results show that the
      activatable (membrane-inserted) IGF-1r and stable microtubules accumulate in the
      same neurite of cells at stage 2. The polarized insertion of IGF-1r depends on
      microtubule dynamics as shown using drugs which modify microtubule stability.
      Silencing of KIF5C expression prevents the polarized insertion of IGF-1r into the
      neuronal plasmalemma and neuronal polarization. Syntaxin 6 and VAMP4, necessary
      for the polarized insertion of the IGF-1r, are associated to vesicles carried by
      the microtubular motor KIF5C and is transported preferentially to the neurite
      where KIF5C accumulates. We conclude that the enrichment of stable microtubules
      in the future axon enhances KIF5C-mediated vesicular transport of syntaxin 6 and
      VAMP4, which in turn mediates the polarized insertion of IGF-1r in the
      plasmalemma, a key step for neuronal polarization. We herewith establish a
      mechanistic link between three early polarity events necessary for the
      establishment of neuronal polarity.

PMID- 27699601
TI  - Generation of a Functional Human Neural Network by NDM29 Overexpression in
      Neuroblastoma Cancer Cells.
AB  - Recent advances in life sciences suggest that human and rodent cell responses to
      stimuli might differ significantly. In this context, the results achieved in
      neurotoxicology and biomedical research practices using neural networks obtained
      from mouse or rat primary culture of neurons would benefit of the parallel
      evaluation of the same parameters using fully differentiated neurons with a human
      genetic background, thus emphasizing the current need of neuronal cells with
      human origin. In this work, we developed a human functionally active neural
      network derived by human neuroblastoma cancer cells genetically engineered to
      overexpress NDM29, a non-coding RNA whose increased synthesis causes the
      differentiation toward a neuronal phenotype. These cells are here analyzed
      accurately showing functional and morphological traits of neurons such as the
      expression of neuron-specific proteins and the possibility to generate the
      expected neuronal current traces and action potentials. Their morphometrical
      analysis is carried out by quantitative phase microscopy showing soma and axon
      sizes compatible with those of functional neurons. The ability of these cells to
      connect autonomously forming physical junctions recapitulates that of hippocampal
      neurons, as resulting by connect-ability test. Lastly, these cells self-organize
      in neural networks able to produce spontaneous firing, in which spikes can be
      clustered in bursts. Altogether, these results show that the neural network
      obtained by NDM29-dependent differentiation of neuroblastoma cells is a suitable
      tool for biomedical research practices.

PMID- 27699599
TI  - Linagliptin, a Dipeptidyl Peptidase-4 Inhibitor, Mitigates Cognitive Deficits and
      Pathology in the 3xTg-AD Mouse Model of Alzheimer's Disease.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone shown to be active in the
      treatment of type-2 diabetes (T2D) and has also been shown as efficacious in
      Alzheimer's disease (AD). Dipeptidyl peptidase-4 (DPP-4), an enzyme that is
      expressed in numerous cells, rapidly inactivates endogenous GLP-1. Therefore, DPP
      4 inhibition is employed as a therapeutic avenue to increase GLP-1 levels in the
      management of T2D. The effectiveness of DPP-4 inhibitors in the treatment of AD
      has been reported in various animal models of AD. With this background, the
      present study was designed to examine the effectiveness of linagliptin, a DPP-4
      inhibitor in the 3xTg-AD mouse model of Alzheimer's disease. Nine-month-old 3xTg
      AD mice were administered linagliptin orally (5, 10, and 20 mg/kg) for 8 weeks.
      At the end of the linagliptin treatment, mice were evaluated for cognitive
      ability on the Morris Water Maze and Y-maze. Following cognitive evaluation, mice
      were sacrificed to determine the effect of the linagliptin on brain incretin
      levels, amyloid burden, tau phosphorylation, and neuroinflammation. We confirm
      that linagliptin treatment for 8 weeks mitigates the cognitive deficits present
      in 3xTg-AD mice. Moreover, linagliptin also improves brain incretin levels and
      attenuates amyloid beta, tau phosphorylation as well as neuroinflammation. In
      conclusion, linagliptin possesses neuroprotective properties that may be
      attributed to the improvement of incretin levels in the brain.

PMID- 27699602
TI  - Tauroursodeoxycholic Acid Protects Against Mitochondrial Dysfunction and Cell
      Death via Mitophagy in Human Neuroblastoma Cells.
AB  - Mitochondrial dysfunction has been deeply implicated in the pathogenesis of
      several neurodegenerative diseases. Thus, to keep a healthy mitochondrial
      population, a balanced mitochondrial turnover must be achieved.
      Tauroursodeoxycholic acid (TUDCA) is neuroprotective in various neurodegenerative
      disease models; however, the mechanisms involved are still incompletely
      characterized. In this study, we investigated the neuroprotective role of TUDCA
      against mitochondrial damage triggered by the mitochondrial uncoupler carbonyl
      cyanide m-chlorophelyhydrazone (CCCP). Herein, we show that TUDCA significantly
      prevents CCCP-induced cell death, ROS generation, and mitochondrial damage. Our
      results indicate that the neuroprotective role of TUDCA in this cell model is
      mediated by parkin and depends on mitophagy. The demonstration that
      pharmacological up-regulation of mitophagy by TUDCA prevents neurodegeneration
      provides new insights for the use of TUDCA as a modulator of mitochondrial
      activity and turnover, with implications in neurodegenerative diseases.

PMID- 27699603
TI  - C-Terminal Binding Protein is Involved in Promoting to the Carcinogenesis of
      Human Glioma.
AB  - C-terminal binding protein (CtBP) is responsible for regulating the pathogenesis
      of a lot of cancer types. However, whether CtBP1/2 is involved in regulating the
      growth and development of human glioma is still obscure. In the present study
      presented here, our results firstly reveal that CtBP1/2 deficiency, induced by
      siRNA interference, disrupts the functional integrity of the MRN complex that is
      responsible for DNA repair in human glioma cells. The dysfunction of the MRN
      complex further contributes to the up-regulation of ATM and Rad3-related kinase
      (ATR) and Chk1 signaling pathway, which inhibits cell cycle progression mediated
      by CDK2, preparing for the initiation of DNA repair. Under the condition of
      hypoxia, hypoxia-inducible factor-1alpha (HIF-1alpha) can be directly regulated
      by CDK2 on protein level, playing coordinately regulatory role in the
      carcinogenesis of human glioma cells. Overall, our findings reveal that CtBP1/2
      is essential to promote to human glioma cell growth through maintaining the DNA
      stability regulated by the MRN/ATR/Chk1/CDK2/HIF-1alpha signaling pathway.

PMID- 27699604
TI  - Epigenetic Regulation of SNAP25 Prevents Progressive Glutamate Excitotoxicty in
      Hypoxic CA3 Neurons.
AB  - Exposure to global hypoxia and ischemia has been reported to cause
      neurodegeneration in the hippocampus with CA3 neurons. This neuronal damage is
      progressive during the initial phase of exposure but maintains a plateau on
      prolonged exposure. The present study on Sprague Dawley rats aimed at
      understanding the underlying molecular and epigenetic mechanisms that lead to
      hypoxic adaptation of CA3 neurons on prolonged exposure to a global hypoxia. Our
      results show stagnancy in neurodegeneration in CA3 region beyond 14 days of
      chronic exposure to hypobaria simulating an altitude of 25,000 ft. Despite
      increased synaptosomal glutamate and higher expression of NR1 subunit of NMDA
      receptors, we observed decrease in post-synaptic density and accumulation of
      synaptic vesicles at the pre-synaptic terminals. Molecular investigations
      involving western blot and real-time PCR showed duration-dependent decrease in
      the expression of SNAP-25 resulting in reduced vesicular docking and synaptic
      remodeling. ChIP assays for epigenetic factors showed decreased expression of
      H3K9Ac and H3K14Ac resulting in SNAP-25 promoter silencing during prolonged
      hypoxia. Administration of sodium butyrate, a non-specific HDAC inhibitor, during
      21 days hypoxic exposure prevented SNAP-25 downregulation but increased CA3
      neurodegeneration. This epigenetic regulation of SNAP-25 promoter was independent
      of increased DNMT3b expression and promoter methylation. Our findings provide a
      novel insight into epigenetic factors-mediated synaptic remodeling to prevent
      excitotoxic neurodegeneration on prolonged exposure to global hypobaric hypoxia.

PMID- 27699606
TI  - Long-term changes in subfoveal choroidal thickness and central macula thickness
      after Nd:YAG laser capsulotomy.
AB  - PURPOSE: To evaluate changes in central macula thickness (CMT), subfoveal choroid
      thickness (SCT), and intraocular pressure (IOP) before and after
      neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy. METHODS: 42 eyes of
      42 patients who underwent Nd:YAG laser capsulotomy were included in this
      prospective study. CMT, SCT, and IOP were evaluated preoperatively and at
      postoperative week 1 and postoperative months 1, 3, 6, and 12. RESULTS: CMT was
      238.1 +/- 27.6 MUm (mean +/- SD) preoperatively, then 239.7 +/- 29.8, 241.3 +/-
      28.7, 242.7 +/- 27.2, 238.8 +/- 23.7, and 238.3 +/- 21.7 MUm at postoperative
      week 1 and months 1, 3, 6, and 12, respectively. SCT was 263.3 +/- 21.6 MUm
      preoperatively, and 265.5 +/- 24.8, 266.2 +/- 25.7, 267.1 +/- 26.3, 269.1 +/-
      24.2, and 269.9 +/- 21.4 MUm at postoperative week 1 and months 1, 3, 6, and 12,
      respectively. There were no significant differences between preoperative and
      postoperative results for CMT, SCT, or IOP (all p > 0.05). CONCLUSION: Although
      there were slight changes in choroid thickness in the long term, treatment of
      posterior capsule opacification with a low-energy Nd:YAG laser is a safe
      procedure that increases visual acuity without creating a significant increase in
      IOP, CMT, and SCT.

PMID- 27699605
TI  - Femtosecond laser-assisted LASIK versus PRK for high myopia: comparison of 18
      month visual acuity and quality.
AB  - PURPOSE: To compare 18-month outcomes between femtosecond laser-assisted LASIK
      (femto-LASIK) and photorefractive keratectomy with mitomycin-C (PRK-MMC) for
      myopia of more than 7.0 D in terms of visual acuity and quality. METHODS: In this
      comparative nonrandomized clinical trial, 60 eyes from 30 patients (30 eyes in
      each group) were enrolled. The two procedures were compared in terms of 18-month
      changes in uncorrected distance visual acuity (UDVA), corrected distance visual
      acuity (CDVA), manifest refraction spherical equivalent, ocular and corneal
      higher order aberrations (HOAs), and contrast sensitivity (CS). RESULTS: Mean
      myopia was -8.65 +/- 1.51 and -8.04 +/- 1.70 D (P = 0.149) and mean ablation
      depth was 109.37 +/- 9.07 and 105.09 +/- 12.59 um (P = 0.138), in the femto-LASIK
      and PRK-MMC groups, respectively. Baseline parameters were not significantly
      different between the two groups (all P > 0.05). At 18 months postoperatively, 75
      % in the femto-LASIK, versus 57.1 % in the PRK-MMC group, had 20/20 UDVA (P =
      0.017). CDVA remained similarly unchanged in both groups (P = 0.616). No case had
      residual refractive error more than 1.0 D in the femto-LASIK group, while 33.5 %
      in the other group had more than 1.0 D residual error (P = 0.390). Changes in
      corneal HOA were not significantly different between the two groups (P = 0.260).
      Cases in the femto-LASIK group showed more increase in ocular HOA (P = 0.032) and
      coma (P = 0.083, power = 72 %). CS remained similarly unchanged in all spatial
      frequencies in both groups (all P > 0.05). CONCLUSION: Although femto-LASIK
      induces more HOA compared to PRK-MMC, considering outcomes in terms of 20/20
      UDVA, residual refractive error, and CS stability, femto-LASIK provides more
      favorable results than PRK-MMC in high myopia.

PMID- 27699607
TI  - To assess the efficacy of vertical muscle surgery for management of hypotropia in
      monocular elevation deficiency type II.
AB  - AIM: To assess the efficacy of vertical muscle surgery for management of
      hypotropia in monocular elevation deficiency (MED) type II. Knapp's is described
      as standard procedure for management of MED type II. However, it is not graded
      and has unpredictable amount of correction. Besides this, there is drift towards
      overcorrection with time and limitation of movements in extreme adduction and
      abduction. MED is a vertical misalignment for which vertical muscle surgery is
      also described but limited literature is available. METHODS: Thirteen fresh cases
      of MED type II with hypotropia >20 PD and age >4 years were included in our
      interventional study. All cases underwent superior rectus resection and inferior
      rectus recession (vertical R&R) depending upon amount of preoperative deviation.
      Success was defined as hypotropia <5 PD at 1-year follow-up. RESULTS: Twelve
      patients (92.30 %) were aligned to within 5 PD. Six patients (46.15 %) had gain
      in elevation. Bell's phenomenon was improved in six patients (46.15 %). There was
      no limitation in down gaze in any patient. None gained stereopsis. CONCLUSION:
      Vertical R&R is a good alternative for MED type II with predictable amount of
      correction especially in patients with higher preoperative deviation. It spares
      horizontal muscles for correction of any associated horizontal deviation.

PMID- 27699608
TI  - Sarcopenia as a Novel Preoperative Prognostic Predictor for Survival in Patients
      with Bladder Cancer Undergoing Radical Cystectomy.
AB  - PURPOSE: To investigate the prognostic significance of sarcopenia on long-term
      outcomes in patients with bladder cancer after radical cystectomy (RC). METHODS:
      We retrospectively reviewed 136 patients undergoing RC for urothelial carcinoma
      at our institution. Prognostic impact of the preoperative clinical, laboratory,
      and radiologic parameters were evaluated by Cox proportional hazard model
      analyses, and a nomogram was developed to predict cancer-specific survival (CSS)
      after RC. RESULTS: The mean follow-up was 46.7 months. Patients with sarcopenia
      had a significantly shorter CSS than those without sarcopenia. On univariate Cox
      analysis, clinical T stage, histology of transurethral resection of bladder tumor
      (TURBT) specimen, pretreatment hemoglobin, pretreatment neutrophil-to-lymphocyte
      ratio (NLR), pretreatment serum C-reactive protein level, pretreatment serum
      albumin level, presence of hydronephrosis, and presence of sarcopenia were
      associated with significantly worse CSS. On multivariate Cox stepwise analysis,
      sarcopenia (hazard rate [HR] = 2.3, p = 0.015), clinical T stage (cT4: HR = 5.3;
      p = 0.0096), presence of hydronephrosis (HR = 2.0; p = 0.033), histology of TURBT
      specimen (HR = 2.2, p = 0.044), and NLR (HR = 1.3; p = 0.0048) were significant
      independent predictors of an unfavorable prognosis Based on the results of the
      multivariate analysis, we developed a nomogram to predict 1-, 3-, and 5-year CSS
      after RC. CONCLUSIONS: Sarcopenia, clinical T stage, presence of hydronephrosis,
      histology of TURBT specimen, and NLR are novel preoperative prognostic factors
      even after adjustment for other known preoperative predictors in patients
      undergoing RC for bladder cancer.

PMID- 27699609
TI  - Preoperative Serum Carcinoembryonic Antigen Level as a Prognostic Factor for
      Recurrence and Survival After Curative Resection Followed by Adjuvant
      Chemotherapy in Stage III Colon Cancer.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) is the most widely used tumor marker
      in colon cancer; however, there has been controversy regarding the significance
      of preoperative serum CEA level as a prognostic factor for recurrence. In this
      study, we evaluated the optimal cutoff value and prognostic significance of
      preoperative serum CEA level in stage III colon cancer. METHODS: Based on a
      retrospective cohort of 965 patients with stage III colon cancer who underwent
      elective curative surgery and adjuvant chemotherapy with fluoropyrimidine and
      oxaliplatin (training set), we determined the optimal cutoff value of CEA for
      recurrence using the Contal and O'Quigley method. We assessed the prognostic
      value of this cutoff value in terms of disease-free survival (DFS) and overall
      survival (OS) in a prospective cohort of 268 patients with stage III colon cancer
      (validation set). A Cox proportional hazards model was used to explore the
      association of prognostic variables with DFS and OS. RESULTS: The statistically
      determined best cutoff value for CEA was 3 ng/mL in the training set. A high CEA
      level (>=3 ng/mL) was associated with inferior DFS (hazard ratio [HR] 4.609, 95 %
      confidence interval [CI] 2.028-10.474) and OS (HR 3.956, 95 % CI 1.127-13.882) in
      the validation set, while multivariate analysis showed that a high CEA level was
      an independent risk factor for DFS and OS in both study subsets. CONCLUSION:
      Preoperative serum CEA level is an independent prognostic factor for DFS and OS
      in patients with stage III colon cancer after curative resection and adjuvant
      chemotherapy.

PMID- 27699610
TI  - Patterns of Local Recurrence and Oncologic Outcomes in T3 Low Rectal Cancer (<=5
      cm from the Anal Verge) Treated With Short-Course Radiotherapy With Delayed
      Surgery : Outcomes in T3 Low Rectal Cancer Treated With Short-Course Radiotherapy
      With Delayed Surgery.
AB  - BACKGROUND: Short-course radiotherapy with delayed surgery (SRT-delay) is still
      under clinical investigation for its efficacy in treating low rectal cancer (<=5
      cm from the anal verge). This study was designed to assess the pattern of local
      recurrence and oncologic outcomes in T3 low rectal cancer treated with SRT-delay.
      METHODS: This study enrolled T3 low rectal cancer patients without distant
      metastasis between 2003 and 2015. All patients received total mesorectal excision
      following SRT-delay (25 Gy/10 fractions/5 days + S-1 radiosensitizer with a 4
      week delay of surgery). The median follow-up period was 69 (range 1-149) months.
      RESULTS: A total 119 consecutive patients had low rectal cancer; 104 (87.4 %)
      underwent intersphincteric resection (ISR), and 15 (12.6 %) underwent
      abdominoperineal resection (APR). Fifty-six patients (47.1 %) were ypT
      downstaged, 86 (72.2 %) were ypN0, and 10 (8.4 %) had circumferential resection
      margin involvement. The 5-year local recurrence-free survival, recurrence-free
      survival, and overall survival were 93.0, 76.2, and 80.5 %, respectively. Nine
      patients experienced local recurrence: lateral pelvic recurrence in six patients
      (5.0 %) and central pelvic recurrence in three (2.5 %). CONCLUSIONS: A total of
      87.4 % of sphincter-preserving surgeries were performed for T3 low rectal cancer
      following SRT-delay. Pathological tumor downstaging, circumferential resection
      margin involvement, local recurrence, and oncologic outcomes were acceptable;
      therefore, the SRT-delay regimen may be an option for treating T3 low rectal
      cancer.

PMID- 27699611
TI  - Robotic Right Colectomy with Modified Complete Mesocolic Excision: Long-Term
      Oncologic Outcomes.
AB  - BACKGROUND: A modified complete mesocolic excision (mCME) technique for the
      treatment of right-sided colon cancer recently was shown by Hohenberger and
      colleagues to provide impressive long-term oncologic outcomes. This report aims
      to describe the authors' experience with robotic right colectomy using mCME. The
      safety, feasibility, and efficacy of this procedure are measured by
      complications, conversion rates, and 4-year oncologic outcomes. METHODS: A
      retrospective study analyzed 100 consecutive patients who underwent robotic right
      colectomy with mCME and intracorporeal anastomosis at the authors' institution
      between November 2005 and November 2013. Intra- and postoperative clinical
      outcomes, pathologic data, and survival were analyzed. RESULTS: Robotic right
      colectomy with mCME was successfully performed for all the patients. No
      conversions or intraoperative complications occurred. The major complication rate
      (Dindo 3 or 4) was 4 %. During a median follow-up period of 48.5 months (range 24
      114 months), the survival rates were 94.5 % for disease-specific survival, 91.4 %
      for disease-free survival, and 90.3 % for overall survival. CONCLUSIONS: The
      authors' experience confirms the feasibility and safety of mCME for the treatment
      of right-sided colon cancer. This technique provided satisfying short-term
      outcomes with promising 4-year oncologic results. However, the real benefits of
      the CME technique should be evaluated further by well-conducted randomized
      studies before its adoption in routine practice is recommended.

PMID- 27699614
TI  - Abstracts accepted for American Conference on Pharmacometrics 2016 (ACoP7).

PMID- 27699613
TI  - The American Conference on Pharmacometrics 2016 (ACoP7).

PMID- 27699615
TI  - Program (ACoP7).

PMID- 27699612
TI  - A quantitative RT-PCR assay for rapid detection of Eurasian-lineage H10 subtype
      influenza A virus.

PMID- 27699616
TI  - Backbone and methyl resonance assignments of the 42 kDa human Hsc70 nucleotide
      binding domain in the ADP state.
AB  - Hsc70 is the constitutively expressed mammalian heat shock 70 kDa (Hsp70)
      cytosolic chaperone. It plays a central role in cellular proteostasis and protein
      trafficking. Here, we present the backbone and methyl group assignments for the
      386-residue nucleotide binding domain of the human protein. This domain controls
      the chaperone's allostery, binds multiple co-chaperones and is the target of
      several classes of known chemical Hsp70 inhibitors. The NMR assignments are based
      on common triple resonance experiments with triple labeled protein, and on
      several 15N and 13C-resolved 3D NOE experiments with methyl-reprotonated samples.
      A combination of computer and manual data interpretation was used.

PMID- 27699617
TI  - Backbone and side-chain resonance assignments of Plasmodium falciparum SUMO.
AB  - One of the most debilitating diseases Malaria, in its different forms, is caused
      by protozoan of Plasmodium species. Deadliest among these forms is the "cerebral
      malaria" which is afflicted upon by Plasmodium falciparum. Plasmodium adopts
      numerous strategies including various post-translational modifications (PTMs) to
      infect and survive in the human host. These PTMs have proven their critical
      requirement in the Plasmodium biology. Recently, sumoylation has been
      characterized as one of the important PTMs and many of its putative substrates
      have been identified in Plasmodium. Sumoylation is the covalent attachment of
      SUMO protein to the substrate protein, which is mediated by an enzyme cascade
      involving activating (E1), conjugating (E2), and ligating enzymes (E3). Here, we
      report resonance assignment for 1H, 13C and 15N of Plasmodium falciparum SUMO (Pf
      SUMO) protein determined by various 2D and 3D heteronuclear NMR experiments along
      with predicted secondary structures.

PMID- 27699618
TI  - Implementation of a Multidisciplinary Guideline for Low Back Pain: Process
      Evaluation Among Health Care Professionals.
AB  - Background To reduce the burden of low back pain (LBP) in the Netherlands, a
      multidisciplinary guideline for LBP has been implemented in Dutch primary care
      using a multifaceted implementation strategy targeted at health care
      professionals (HCPs) and patients. The current paper describes the process
      evaluation of the implementation among HCPs. Methods The strategy aimed to
      improve multidisciplinary collaboration and communication, and consisted of 7
      components. This process evaluation was performed using the Linnan and Steckler
      framework. Data were collected using a mixed methods approach of quantitative and
      qualitative data. Results 128 HCPs participated in the implementation study, of
      which 96 participated in quantitative and 21 participated in qualitative
      evaluation. Overall dose delivered for this study was 89 %, and the participants
      were satisfied with the strategy, mostly with the multidisciplinary approach,
      which contributed to the mutual understanding of each other's disciplines and
      perspectives. While the training sessions did not yield any new information, the
      strategy created awareness of the guideline and its recommendations, contributing
      to positively changing attitudes and aiding in improving guideline adherent
      behaviour. However, many barriers to implementation still exist, including
      personal and practical factors, confidence, dependence and distrust issues among
      the HCPs, as well as policy factors (e.g. reimbursement systems). Conclusions The
      data presented in this paper have shown that the strategy that was used to
      implement the guideline in a Dutch primary care setting was feasible, especially
      when using a multidisciplinary approach. However, identified barriers for
      implementation have been identified and should be addressed in future
      implementation.

PMID- 27699619
TI  - Commentary of the Special Panel at the Hopkinton Conference Working Group on
      Workplace Disability Prevention.

PMID- 27699621
TI  - Computer-aided diagnosis system for lung nodules based on computed tomography
      using shape analysis, a genetic algorithm, and SVM.
AB  - Lung cancer is the major cause of death among patients with cancer worldwide.
      This work is intended to develop a methodology for the diagnosis of lung nodules
      using images from the Image Database Consortium and Image Database Resource
      Initiative (LIDC-IDRI). The proposed methodology uses image processing and
      pattern recognition techniques. To differentiate the patterns of malignant and
      benign forms, we used a Minkowski functional, distance measures, representation
      of the vector of points measures, triangulation measures, and Feret diameters.
      Finally, we applied a genetic algorithm to select the best model and a support
      vector machine for classification. In the test stage, we applied the proposed
      methodology to 1405 (394 malignant and 1011 benign) nodules from the LIDC-IDRI
      database. The proposed methodology shows promising results for diagnosis of
      malignant and benign forms, achieving accuracy of 93.19 %, sensitivity of 92.75
      %, and specificity of 93.33 %. The results are promising and demonstrate a good
      rate of correct detections using the shape features. Because early detection
      allows faster therapeutic intervention, and thus a more favorable prognosis for
      the patient, herein we propose a methodology that contributes to the area.

PMID- 27699620
TI  - Influence of Early Onset of Alcohol Use on the Development of Adolescent Alcohol
      Problems: a Longitudinal Binational Study.
AB  - This study examined cross-national similarities in a developmental model linking
      early age of alcohol use onset to frequent drinking and heavy drinking and
      alcohol problems 1 and 2 years later in a binational sample of 13-year-old
      students from two states: Washington State, USA and Victoria, Australia (N =
      1833). A range of individual, family, school, and peer influences was included in
      analyses to investigate their unique and shared contribution to development of
      early and more serious forms of alcohol use and harms from misuse. Data were
      collected annually over a 3-year period from ages 13 to 15. Analyses were
      conducted using multiple-group structural equation modeling. For both states,
      early use of alcohol predicted frequent drinking, which predicted alcohol
      problems. Family protective influences had neither direct effects on heavy
      drinking nor effects on alcohol harm in either state, whereas school protection
      directly reduced the risk of heavy drinking in both states. Exposure to
      antisocial peers and siblings predicted a higher likelihood of heavy drinking and
      alcohol harm for students in both Washington and Victoria. Implications for the
      prevention of adolescent alcohol problems are discussed.

PMID- 27699623
TI  - Clinical Pharmacokinetics and Pharmacodynamics of Insulin Glargine 300 U/mL.
AB  - Concentrated insulin analogs have recently been approved and are available for
      clinical use in the management of diabetes mellitus. One new product is insulin
      glargine U-300 (Sanofi), a basal concentrated insulin of 300 U/mL. Several
      studies have been conducted and completed evaluating blood samples for the
      pharmacokinetics of insulin glargine U-300 and euglycemic clamp procedures for
      the pharmacodynamics. This concentrated insulin has a low within-day variability
      and high day-to-day reproducibility, allowing for a more constant and prolonged
      duration of action, compared with insulin glargine U-100 (100 U/mL). Insulin
      glargine U-300 is equally effective, when compared with insulin glargine U-100
      for glycemic control in patients with type 1 and 2 diabetes mellitus. Insulin
      glargine U-300 has a similar efficacy profile to insulin glargine U-100 for
      glycemic control, yet with lower rates of nocturnal and severe hypoglycemia.
      Insulin glargine U-300 can be considered an acceptable basal insulin for patients
      with type 1 and 2 diabetes mellitus, and it has a potential role among patients
      who are naive to insulin therapy or require titration of basal insulin. Titration
      of insulin glargine U-300 would result in less volume and a lower risk of
      hypoglycemia, compared with insulin glargine U-100. This article evaluates and
      summarizes the pharmacokinetics and pharmacodynamics of insulin glargine U-300,
      for patients with type 1 or 2 diabetes mellitus, and summarizes its application
      to clinical practice.

PMID- 27699624
TI  - Time to Progression of Pancreatic Cancer: Evaluation with Multi-Detector Computed
      Tomography.
AB  - PURPOSE: The aim of this study is to evaluate the natural history of untreated
      pancreatic cancer, with a particular emphasis on the growth rate of primary tumor
      and development of metastatic disease. METHODS: One hundred patients with
      histologically proven pancreatic ductal adenocarcinoma examined with at least two
      CT scans with no intervening treatment were included. Tumor diameters and volumes
      were measured in CT scans and tumor growth rates and volume doubling times (VDTs)
      were calculated. The relationship between initial tumor size, growth rate, and
      distant metastasis development were investigated. RESULTS: Included tumors were
      1.0-6.2 cm (mean, 2.9 +/- 1.3 cm) in diameter and 5.5-1225.9 cm3 (mean, 120.6 +/-
      158.9 cm3) in volume at the initial CT. Tumor growth rates were -0.4 to 19.9
      cm/year (mean, 4.2 +/- 3.8 cm/year) in diameter, and 11.1-13,321.5 cm3/year
      (mean, 727.8 +/- 1609.5 cm3/year) in volume corresponding to VDT of 20.0-976.8
      days (mean, 132.3 +/- 132.1 days). The growth rate was significantly associated
      with the initial diameter and volume (p < 0.001). The development of distant
      metastasis was significantly associated with initial diameter (p < 0.05), volume
      (p = 0.015), and volume growth rate (p = 0.002). CONCLUSIONS: The growth rate and
      VDTs of untreated pancreatic cancers varied widely, from less than a month to
      more than 4 years, positively associated with tumor size. The small tumors tend
      to grow slowly and have low risk for developing metastasis.

PMID- 27699622
TI  - A Two-Way Steady-State Pharmacokinetic Interaction Study of Doravirine (MK-1439)
      and Dolutegravir.
AB  - INTRODUCTION: Doravirine, a non-nucleoside reverse-transcriptase inhibitor in
      development for the treatment of patients with human immunodeficiency virus-1
      infection, has potential to be used concomitantly in antiretroviral therapy with
      dolutegravir, an integrase strand transfer inhibitor. The pharmacokinetic
      interactions between these drugs were therefore assessed. METHODS: Oral
      formulations of doravirine and dolutegravir were dosed both individually and
      concomitantly once daily in healthy adults. Twelve subjects (six were male), 23
      42 years of age, were enrolled and 11 completed this phase I, open-label, three
      period, fixed-sequence study per protocol; one subject was discontinued for a
      positive cotinine test at admission to period 2. In period 1, dolutegravir 50 mg
      was administered for 7 days. After a 7-day washout, doravirine 200 mg was dosed
      for 7 days in period 2, followed (without washout) by both doravirine and
      dolutegravir simultaneously for 7 days in period 3. Plasma samples were taken to
      determine dolutegravir and doravirine concentrations. RESULTS: The steady-state
      concentration 24 h post-dose (C24) of dolutegravir was not substantially altered
      by co-administration of doravirine multiple doses; area under the plasma
      concentration-time curve from dosing to 24 h post-dose (AUC0-24), maximum
      concentration (C max), and C24 geometric mean ratios were 1.36, 1.43, and 1.27,
      respectively. The pharmacokinetics of doravirine was not affected by multiple
      doses of dolutegravir (geometric mean ratios: 1.00, 0.98, and 1.06 for AUC0-24,
      C24, and C max, respectively). Both drugs were generally well tolerated.
      CONCLUSION: The results of this study demonstrate that concomitant administration
      of doravirine and dolutegravir in healthy subjects causes no clinically
      significant alteration in the pharmacokinetic and safety profiles of the two
      drugs, thereby supporting further evaluation of co-administration of these agents
      for human immunodeficiency virus-1 treatment.

PMID- 27699626
TI  - Marijuana Use and Dependence in Chilean Adolescents and Its Association with
      Family and Peer Marijuana Use.
AB  - PURPOSE: The purpose of the study is to examine (1) whether family and peer
      marijuana use are independently related to adolescent marijuana use in Chile, (2)
      whether family and peer marijuana use are associated with adolescent marijuana
      dependence in adolescents using marijuana, and (3) whether the adolescent's age
      moderates the association between family or peer use and adolescent marijuana use
      and/or dependence. METHOD: This study used data from the National Survey on Drug
      Use in the General Population in Chile (a cross-sectional observational study),
      which was conducted in 2008 and 2010 in 4413 adolescents aged 12-19. Adolescents
      answered questions about their past-year marijuana use and dependence (ICD-10
      criteria) and the marijuana use of their family and peers. Logistic regressions
      were performed while controlling for confounders. RESULTS: Adolescents who had a
      family member who used marijuana were five times more likely to use the drug.
      Adolescents with a close friend who used marijuana were eight times more likely
      to use marijuana. When adolescents were using marijuana, they were three times
      more likely to be dependent if they had a family member who used the drug.
      However, no significant relationship was found between peer use and dependence.
      No statistically significant interactions were found between family or peer use
      and age. CONCLUSION: Family and peer marijuana use was independently associated
      with adolescent's past-year marijuana use; however, only family marijuana use was
      statistically associated with adolescent's marijuana dependence.

PMID- 27699625
TI  - Cannabinoids and GI Disorders: Endogenous and Exogenous.
AB  - OPINION STATEMENT: Despite the political and social controversy affiliated with
      it, the medical community must come to the realization that cannabinoids exist as
      a ubiquitous signaling system in many organ systems. Our understanding of
      cannabinoids and how they relate not only to homeostasis but also in disease
      states must be furthered through research, both clinically and in the laboratory.
      The identification of the cannabinoid receptors in the early 1990s have provided
      us with the perfect target of translational research. Already, much has been done
      with cannabinoids and the nervous system. Here, we explore the implications it
      has for the gastrointestinal tract. Most therapeutics currently on the market
      presently target only one aspect of the cannabinoid system. Our main purpose here
      is to highlight areas of research and potential avenues of discovery that the
      cannabinoid system has yet to reveal.

PMID- 27699627
TI  - The Association Between Social Support, Body Mass Index and Increased Risk of
      Prediabetes: the Cardiovascular Risk in Young Finns Study.
AB  - PURPOSE: The psychosocial determinants of prediabetes are poorly understood. The
      aims of our study were (1) to analyse the association between perceived social
      support in young adulthood and fasting glucose levels and prediabetes in mid
      adulthood in a cohort of healthy Finns, (2) to explore whether body mass index
      (BMI), inflammation or depression mediate this relationship, (3) and to examine
      the association between social support trajectory groups and fasting glucose.
      METHOD: A prospective design was used with an analytic sample of 1250
      participants aged 3-18 years at baseline (1980) and aged 12-39 years when social
      support was measured. Fasting glucose and prediabetes were assessed 32 years
      after baseline. Linear and logistic regression was used to examine the
      association between social support and the outcome measures. A bootstrapping
      technique was used to examine mediation effects. RESULTS: Social support was
      associated with future glucose levels in women after adjusting for childhood
      socioeconomic status (SES) and youth depression (beta = -0.136, p = 0.001) and
      also predicted prediabetes in women after adjusting for childhood SES (beta =
      1.31, 95 % CI 1.02 to 1.69, p = 0.031). Both associations were attenuated after
      adjusting for BMI in mid-adulthood. BMI was found to mediate the relationship
      between social support and prediabetes in women (beta for indirect effect beta =
      0.09, SE = 0.03, CI = 0.03 to 0.16). CONCLUSION: Low perceived social support in
      young adulthood is associated with high fasting glucose and prediabetes in mid
      adulthood in women but not men. The association between social support and
      prediabetes in women can be partly explained by BMI.

PMID- 27699629
TI  - Genetic Screening in Pheochromocytoma/Paraganglioma.

PMID- 27699628
TI  - Issues Arising in Psychological Consultations to Help Parents Talk to Minor and
      Young Adult Children about their Cancer Genetic Test Result: a Guide to
      Providers.
AB  - The defining difference between genetic and traditional medicine is that genetic
      findings have implications not just for the patient, but also for their
      relatives. Discussion of a test result between parent and child is both a
      transformative and a translational moment in the life of a family. Parents report
      wanting help in talking to their children. The challenge for genetic counselors
      and other providers is to be able to recognize which issues are at the core of
      parental distress and be able to offer recommendations to empower and support
      parents. The complexity of potential genetic findings, including variants of
      uncertain significance (VUS) and incidental findings have vastly increased,
      requiring considerable explanation and leaving less time for discussion of
      emotional issues. While the nature of the testing (single gene to multigene panel
      and genomic testing) is dramatically changing, the nature of parent concerns
      remains remarkably constant. Families differ in many respects, so no "recipe"
      suffices to answer parents' questions about how this important task should be
      approached in each family. Successful consultation to parents requires true
      counseling, matching parents' fears and questions with information, exploration
      and advice specific to their concerns, their circumstances and strengths.

PMID- 27699632
TI  - Introduction: special issue on operative neurosurgical oncology.

PMID- 27699631
TI  - Estimating the Societal Benefits of THA After Accounting for Work Status and
      Productivity: A Markov Model Approach.
AB  - BACKGROUND: Demand for total hip arthroplasty (THA) is high and expected to
      continue to grow during the next decade. Although much of this growth includes
      working-aged patients, cost-effectiveness studies on THA have not fully
      incorporated the productivity effects from surgery. QUESTIONS/PURPOSES: We asked:
      (1) What is the expected effect of THA on patients' employment and earnings? (2)
      How does accounting for these effects influence the cost-effectiveness of THA
      relative to nonsurgical treatment? METHODS: Taking a societal perspective, we
      used a Markov model to assess the overall cost-effectiveness of THA compared with
      nonsurgical treatment. We estimated direct medical costs using Medicare claims
      data and indirect costs (employment status and worker earnings) using regression
      models and nonparametric simulations. For direct costs, we estimated average
      spending 1 year before and after surgery. Spending estimates included physician
      and related services, hospital inpatient and outpatient care, and postacute care.
      For indirect costs, we estimated the relationship between functional status and
      productivity, using data from the National Health Interview Survey and regression
      analysis. Using regression coefficients and patient survey data, we ran a
      nonparametric simulation to estimate productivity (probability of working
      multiplied by earnings if working minus the value of missed work days) before and
      after THA. We used the Australian Orthopaedic Association National Joint
      Replacement Registry to obtain revision rates because it contained osteoarthritis
      specific THA revision rates by age and gender, which were unavailable in other
      registry reports. Other model assumptions were extracted from a previously
      published cost-effectiveness analysis that included a comprehensive literature
      review. We incorporated all parameter estimates into Markov models to assess THA
      effects on quality-adjusted life years and lifetime costs. We conducted threshold
      and sensitivity analyses on direct costs, indirect costs, and revision rates to
      assess the robustness of our Markov model results. RESULTS: Compared with
      nonsurgical treatments, THA increased average annual productivity of patients by
      USD 9503 (95% CI, USD 1446-USD 17,812). We found that THA increases average
      lifetime direct costs by USD 30,365, which were offset by USD 63,314 in lifetime
      savings from increased productivity. With net societal savings of USD 32,948 per
      patient, total lifetime societal savings were estimated at almost USD 10 billion
      from more than 300,000 THAs performed in the United States each year.
      CONCLUSIONS: Using a Markov model approach, we show that THA produces societal
      benefits that can offset the costs of THA. When comparing THA with other
      nonsurgical treatments, policymakers should consider the long-term benefits
      associated with increased productivity from surgery. LEVEL OF EVIDENCE: Level
      III, economic and decision analysis.

PMID- 27699630
TI  - A Gap in Time: Extending our Knowledge of Temporal Processing Deficits in the HIV
      1 Transgenic Rat.
AB  - Approximately 50 % of HIV-1 seropositive individuals develop HIV-1 associated
      neurocognitive disorders (HAND), which commonly include alterations in executive
      functions, such as inhibition, set shifting, and complex problem solving.
      Executive function deficits in HIV-1 are fairly well characterized, however,
      relatively few studies have explored the elemental dimensions of neurocognitive
      impairment in HIV-1. Deficits in temporal processing, caused by HIV-1, may
      underlie the symptoms of impairment in higher level cognitive processes.
      Translational measures of temporal processing, including cross-modal prepulse
      inhibition (PPI), gap-prepulse inhibition (gap-PPI), and gap threshold detection,
      were studied in mature (ovariectomized) female HIV-1 transgenic (Tg) rats, which
      express 7 of the 9 HIV-1 genes constitutively throughout development. Cross-modal
      PPI revealed a relative insensitivity to the manipulation of interstimulus
      interval (ISI) in HIV-1 Tg animals in comparison to control animals, extending
      previously reported temporal processing deficits in HIV-1 Tg rats to a more
      advanced age, suggesting the permanence of temporal processing deficits. In gap
      PPI, HIV-1 Tg animals exhibited a relative insensitivity to the manipulation of
      ISI in comparison to control animals. In gap-threshold detection, HIV-1 Tg
      animals displayed a profound differential sensitivity to the manipulation of gap
      duration. Presence of the HIV-1 transgene was diagnosed with 91.1 % accuracy
      using gap threshold detection measures. Understanding the generality and
      permanence of temporal processing deficits in the HIV-1 Tg rat is vital to
      modeling neurocognitive deficits observed in HAND and provides a key target for
      the development of a diagnostic screening tool.

PMID- 27699633
TI  - Antibody-Based Drugs and Approaches Against Amyloid-beta Species for Alzheimer's
      Disease Immunotherapy.
AB  - Alzheimer's disease (AD), one of the most devastating diseases for the older
      population, has become a major healthcare burden in the increasingly aging
      society worldwide. Currently, there are still only symptomatic treatments
      available on the market, just to slow down disease progression. In the past
      decades, extensive research focusing on the development of immunotherapy using
      monoclonal antibodies (mAbs) as potential "disease-modifying drugs" has shown
      promise in inhibiting or clearing the formation of toxic amyloid-beta (Abeta)
      species, the suspected causative agents of AD. As a result, these potential life
      saving drugs can break the amyloid cascade, cease neurodegeneration, and prevent
      further reduction in cognitive and physical function. In this review, we first
      describe the polymorphisms of Abeta species, comprising three different pools,
      including monomers, soluble oligomers, and insoluble fibrils, with each pool
      encompassing multiple structures of Abeta aggregation. A comprehensive review on
      their toxicities follows in relation to the characterized epitopes of anti-Abeta
      mAb candidates under development. We then present the outcomes of these mAbs in
      clinical or pre-clinical trials and conclude by providing a summary of other
      novel and promising antibody-based immunotherapeutic approaches that deserve more
      attention for the effective treatment of AD in the future.

PMID- 27699635
TI  - Optimizing CT technique to reduce radiation dose: effect of changes in kVp,
      iterative reconstruction, and noise index on dose and noise in a human cadaver.
AB  - For assessment of the effect of varying the peak kilovoltage (kVp), the adaptive
      statistical iterative reconstruction technique (ASiR), and automatic dose
      modulation on radiation dose and image noise in a human cadaver, a cadaver torso
      underwent CT scanning at 80, 100, 120 and 140 kVp, each at ASiR settings of 0, 30
      and 50 %, and noise indices (NIs) of 5.5, 11 and 22. The volume CT dose index
      (CTDIvol), image noise, and attenuation values of liver and fat were analyzed for
      20 data sets. Size-specific dose estimates (SSDEs) and liver-to-fat contrast-to
      noise ratios (CNRs) were calculated. Values for different combinations of kVp,
      ASiR, and NI were compared. The CTDIvol varied by a power of 2 with kVp values
      between 80 and 140 without ASiR. Increasing ASiR levels allowed a larger decrease
      in CTDIvol and SSDE at higher kVp than at lower kVp while image noise was held
      constant. In addition, CTDIvol and SSDE decreased with increasing NI at each kVp,
      but the decrease was greater at higher kVp than at lower kVp. Image noise
      increased with decreasing kVp despite a fixed NI; however, this noise could be
      offset with the use of ASiR. The CT number of the liver remained unchanged
      whereas that of fat decreased as the kVp decreased. Image noise and dose vary in
      a complicated manner when the kVp, ASiR, and NI are varied in a human cadaver.
      Optimization of CT protocols will require balancing of the effects of each of
      these parameters to maximize image quality while minimizing dose.

PMID- 27699634
TI  - Use of a C1 Inhibitor Concentrate in Adults >=65 Years of Age with Hereditary
      Angioedema: Findings from the International Berinert(r) (C1-INH) Registry.
AB  - BACKGROUND: Treatment of hereditary angioedema (HAE) in 'older adults' (those
      aged >=65 years) has not been well studied. The international Berinert Patient
      Registry collected data on the use of intravenous plasma-derived, pasteurized,
      nanofiltered C1-inhibitor concentrate (pnfC1-INH; Berinert(r)/CSL Behring) in
      patients of any age, including many older adults. METHODS: This observational
      registry, conducted from 2010 to 2014 at 30 US and seven European sites, gathered
      prospective (post-enrollment) and retrospective (pre-enrollment) usage and
      adverse event (AE) data on subjects treated with pnfC1-INH. RESULTS: The registry
      documented 1701 pnfC1-INH infusions in 27 older adults. A total of 1511 HAE
      attacks treated with pnfC1-INH administration were reported among 25 of the 27
      (92.6 %) older adults. Among the older adults, mean (standard deviation [SD])
      (8.8 [4.1] IU/kg) and median (6.4 IU/kg) pnfC1-INH doses were lower than those
      reported for 252 'younger adults' (those aged <65 years: 12.9 [6.2], 12.5 IU/kg,
      respectively). A total of 19 AEs occurred in 8 of 23 (34.8 %) older adults with
      prospective data, for rates of 0.83 events per subject and 0.02 events per
      infusion, similar to corresponding rates in younger adults (0.91 and 0.03,
      respectively). None of the AEs were considered related to pnfC1-INH, and all but
      two events (prostatectomy, gastrointestinal bleeding) were mild or moderate in
      severity. Administration of pnfC1-INH outside of a healthcare setting was
      reported for 1609 infusions in 16 older adults, representing 94.6 % of all pnfC1
      INH infusions in this age group. There were no recorded instances of difficulty
      with self-administration of intravenous pnfC1-INH. CONCLUSIONS: These findings
      suggest a high degree of safety with intravenous pnfC1-INH use in older adults
      with HAE, regardless of administration setting. Trial Registration
      Clinicaltrials.gov NCT01108848.

PMID- 27699636
TI  - Relation between one- and two-dimensional noise power spectra of magnetic
      resonance images.
AB  - Our purpose in this study was to elucidate the relation between the one
      dimensional (1D) and two-dimensional (2D) noise power spectra (NPSs) in magnetic
      resonance imaging (MRI). We measured the 1D NPSs using the slit method and the
      radial frequency method. In the slit method, numerical slits 1 pixel wide and L
      pixels long were placed on a noise image (128 * 128 pixels) and scanned in the MR
      image domain. We obtained the 1D NPS using the slit method (1D NPS_Slit) and the
      2D NPS of the noise region scanned by the slit (2D NPS_Slit). We also obtained 1D
      NPS using the radial frequency method (1D NPS_Radial) by averaging the NPS values
      on the circumference of a circle centered at the origin of the original 2D NPS.
      The properties of the 1D NPS_Slits varied with L and the scanning direction in
      PROPELLER MRI. The 2D NPS_Slit shapes matched that of the original 2D NPS, but
      were compressed by L/128. The central line profiles of the 2D NPS_Slits and the
      1D NPS_Slits matched exactly. Therefore, the 1D NPS_Slits reflected not only the
      NPS values on the central axis of the original 2D NPS, but also the NPS values
      around the central axis. Moreover, the measurement precisions of the 1D NPS_Slits
      were lower than those of the 1D NPS_Radial. Consequently, it is necessary to
      select the approach applied for 1D NPS measurements according to the data
      acquisition method and the purpose of the noise evaluation.

PMID- 27699637
TI  - Cytokine profile and maternal depression and anxiety symptoms in mid-pregnancy
      the FinnBrain Birth Cohort Study.
AB  - Maternal prenatal psychological symptoms are associated with child health
      outcomes, e.g., atopic diseases. Altered prenatal functioning of the immune
      system is a potential mechanism linking maternal symptoms with child health.
      Research on prenatal distress and cytokines is warranted. The study population
      comprised consecutive N = 139 women from a general population-based FinnBrain
      Birth Cohort Study. Standardized questionnaires for depressive, overall anxiety,
      and pregnancy-related anxiety symptoms were used. Serum concentrations of
      selected cytokines were analyzed using Multiplex bead arrays from samples drawn
      at the gestational week 24. The concentrations of T helper (Th)2-related
      interleukins (IL)-9 and IL-13 and Th1-related IL-12 correlated positively with
      prenatal depressive and overall anxiety symptom scores (p values, range 0.011
      0.029). Higher interferon (IFN)-gamma/IL-4 ratio (p = 0.039) and Th2-related IL-5
      (p = 0.007) concentration correlated positively with depressive symptoms.
      Pregnancy-related anxiety score correlated positively with IL-12 (p = 0.041), IL
      13 (p = 0.025), and anti-inflammatory IL-10 (p = 0.048) concentrations. IL-6 and
      TNF-alpha concentrations were unrelated to prenatal symptoms. As a novel finding,
      we observed positive correlations between concentrations of potentially
      proallergenic cytokines and maternal prenatal psychological symptoms. Different
      symptom measures may yield distinct cytokine responses. This provides hypotheses
      for studies on mechanisms bridging prenatal stress and child health.

PMID- 27699639
TI  - In Reply: "Single Versus Multiple Hyperbaric Sessions for Carbon Monoxide
      Poisoning in a Murine Model".

PMID- 27699640
TI  - Acute exacerbation of irritable bowel syndrome prevented by prn oral triptan.
AB  - We report a case of irritable bowel syndrome (IBS), diarrhea subtype,
      characterized by daily 'morning rush' and episodic acute exacerbations brought on
      by common IBS trigger foods including insoluble fiber, red wine and large/rich
      meals. The patient also had a history of migraine headaches, and a family history
      suggesting a common diathesis for both disorders. Given hypothesized
      contributions to IBS from dysregulation of the enteric serotonergic system, a
      trial of low-dose triptan medication was implemented in the context of the
      patient's known IBS triggers, with highly satisfactory results.

PMID- 27699642
TI  - Oropharyngeal Syphilis: Imaging and Pathologic Findings in Two Patients.
AB  - Syphilis is a widespread infection with increasing frequency in developed
      countries, especially among men who have sex with men. We present two cases of
      oropharyngeal syphilis in two middle-aged men who presented with a painless
      tonsillar ulcer and progressive enlargement of cervical lymph nodes suspected of
      being a tonsillar tumour. A pathologic analysis of the ulcer led to an accurate
      diagnosis. We review the imaging and pathologic findings to emphasize the
      importance of taking syphilis into account in the differential diagnosis.

PMID- 27699643
TI  - Paliperidone Palmitate Intramuscular 3-Monthly Formulation: A Review in
      Schizophrenia.
AB  - A 3-monthly formulation of intramuscular paliperidone palmitate (3-monthly
      paliperidone palmitate) has recently been approved for the maintenance treatment
      of schizophrenia in adult patients in the EU (Trevicta(r)), following earlier
      approval in the USA (Invega Trinza(r)). This narrative review discusses the
      clinical use of 3-monthly paliperidone palmitate in the maintenance treatment of
      schizophrenia in adult patients and summarizes its pharmacological properties.
      The efficacy of the 3-monthly paliperidone palmitate formulation as a maintenance
      treatment for schizophrenia has been demonstrated in well designed, phase III
      trials. Three-monthly paliperidone palmitate was more effective than placebo in
      delaying time to relapse and reducing relapse rates, and was noninferior to 1
      monthly paliperidone palmitate in the proportion of patients that remained
      relapse-free. The 3-monthly formulation was also more effective than placebo in
      controlling the symptoms of schizophrenia, whilst not differing significantly
      from the 1-monthly formulation in terms of symptomatic control. Three-monthly
      paliperidone palmitate was generally well tolerated in clinical trials, with a
      tolerability profile consistent with that of the 1-monthly formulation. In
      conclusion, 3-monthly paliperidone palmitate is a useful treatment option for
      adult patients with schizophrenia who are adequately treated with the 1-monthly
      formulation, particularly for those who would prefer, or may benefit from, longer
      dosing intervals.

PMID- 27699641
TI  - Recent trends and future directions for the medical treatment of ulcerative
      colitis.
AB  - Recently, several medical treatments for ulcerative colitis (UC) have been
      developed, including 5-aminosalicylic acids (5-ASAs), corticosteroids,
      thiopurine, calcineurin inhibitors, and anti-tumor necrosis factor (TNF) alpha
      treatments. Treatment options including calcineurin inhibitors and anti-TNF
      treatment for refractory UC are discussed in this article. Furthermore, upcoming
      treatments are introduced, such as golimumab, vedolizumab, AJM300, tofacitinib.
      Budesonide foamwill be used as one treatment option in patients with distal
      colitis. Herbal medicine, such as Qing-Dai is also effective for active UC and
      may be useful for patients who are refractory to anti-TNFalpha treatments. In the
      near future, physicians will able to use many different treatments for UC
      patients. However, we should not forget 5-ASA and corticosteroids as the
      fundamental treatments for UC patients.

PMID- 27699645
TI  - Maintaining Weight Loss: an Ongoing Challenge.

PMID- 27699646
TI  - ?

PMID- 27699644
TI  - Chronotherapy: Intuitive, Sound, Founded...But Not Broadly Applied.
AB  - Circadian rhythms are a collection of endogenously driven biochemical,
      physiological, and behavioral processes that oscillate in a 24-h cycle and can be
      entrained by external cues. Circadian clock molecules are responsible for the
      expression of regulatory components that modulate, among others, the cell's
      metabolism and energy consumption. In clinical practice, the regulation of clock
      mechanisms is relevant to biotransformation of therapeutics. Accordingly,
      xenobiotic metabolism and detoxification, the two processes that directly
      influence drug effectiveness and toxicity, are direct manifestations of the daily
      oscillations of the cellular and biochemical processes taking place within the
      gastrointestinal, hepatic/biliary, and renal/urologic systems. Consequently, the
      impact of circadian timing should be factored in when developing therapeutic
      regimens aimed at achieving maximum efficacy, minimum toxicity, and decreased
      adverse effects in a patient. However, and despite a strong mechanistic
      foundation, only 0.16 % of ongoing clinical trials worldwide exploit the concept
      of 'time-of-day' administration to develop safer and more effective therapies. In
      this article, we (1) emphasize points of control at which circadian biology
      intersects critical processes governing treatment interventions; (2) explore the
      extent to which chronotherapeutics are incorporated into clinical trials; (3)
      recognize roadblocks; and (4) recommend approaches to precipitate the integration
      of chronobiological concepts into clinical practice.

PMID- 27699648
TI  - Clinical and Cost Effectiveness of Apixaban Compared to Aspirin in Patients with
      Atrial Fibrillation: An Australian Perspective.
AB  - OBJECTIVE: To determine the clinical and cost effectiveness of apixaban compared
      to aspirin in the prevention of thromboembolic events for patients with atrial
      fibrillation for whom vitamin K antagonist (VKA) therapy (warfarin) has been
      considered unsuitable. METHODS: A previously published Markov model with yearly
      cycles was updated. Information from the Apixaban Versus Acetylsalicylic acid to
      prevent Stroke in Atrial Fibrillation (AVERROES) trial in combination with other
      population data was used to simulate the costs and effects of apixaban compared
      to aspirin over 10 years. The model comprised five health states. Costs from an
      Australian healthcare perspective were estimated from published sources for the
      year 2015. The main outcome of interest was number needed to treat (NNT), number
      needed to harm (NNH), the incremental cost-effectiveness ratio (ICER) [cost per
      quality-adjusted life-year (QALY) gained, and cost per year of life saved
      (YoLS)]. Costs and benefits were discounted at 5.0 % per annum. RESULTS: For each
      patient followed up over 10 years, NNT to prevent one additional event
      (thromboembolic event, death) for apixaban compared to aspirin was 4.6 and 11.8,
      respectively. NNH was 35.9 for non-fatal major bleeding. The model predicted that
      compared to aspirin, apixaban would lead to 0.33 YoLS (discounted) and 0.29 QALYs
      gained (discounted), at an incremental cost of AUD$1996 (discounted). This
      resulted in ICERs of AUD$6011 per YoLS and AUD$6929 per QALY gained. In the
      sensitivity analyses, ICERs were most sensitive to efficacy measures derived from
      the AVERROES study, and time frame. CONCLUSION: Compared to aspirin, apixaban is
      likely to be cost effective in preventing thromboembolic disease among VKA
      unsuitable patients with atrial fibrillation.

PMID- 27699647
TI  - Emerging roles of orphan nuclear receptors in regulation of innate immunity.
AB  - Innate immunity constitutes the first line of defense against pathogenic and
      dangerous insults. However, it is a double-edged sword, as it functions in both
      clearance of infection and inflammatory damage. It is therefore important that
      innate immune responses are tightly controlled to prevent harmful excessive
      inflammation. Nuclear receptors (NRs) are a family of transcription factors that
      play critical roles in various physiological responses. Orphan NRs are a subset
      of NRs for which the ligands and functions are unclear. Accumulating evidence has
      revealed that orphan NRs play essential roles in innate immune responses to
      prevent pathogenic inflammatory responses and to enhance antimicrobial host
      defenses. In this review, we describe current knowledge on the roles and
      mechanisms of orphan NRs in the regulation of innate immune responses. Discovery
      of new functions of orphan NRs would facilitate development of novel preventive
      and therapeutic strategies against human inflammatory diseases.

PMID- 27699649
TI  - A new supramolecular based liquid solid microextraction method for
      preconcentration and determination of trace bismuth in human blood serum and hair
      samples by electrothermal atomic absorption spectrometry.
AB  - A simple and reliable supramolecule-aggregated liquid solid microextraction
      method is described for preconcentration and determination of trace amounts of
      bismuth in water as well as human blood serum and hair samples. Catanionic
      microstructures of cetyltrimethylammonium bromide (CTAB) and sodium dodecyl
      sulfate (SDS) surfactants, dissolved in deionized water/propanol, are used as a
      green solvent to extract bismuth (III)-diethyldithiocarbamate complexes by
      dispersive microextraction methodology. The extracted solid phase is easily
      removed and dissolved in 50 MUL propanol for subsequent measurement by
      electrothermal atomic absorption spectrometry (ET-AAS). The procedure benefits
      the merits of supramolecule aggregates' properties and dispersive microextraction
      technique using water as the main component of disperser solvent, leading to
      direct interaction with analyte. Phase separation behavior of extraction solvent
      and different parameters influencing the extraction efficiency of bismuth ion
      such as salt concentration, pH, centrifugation time, amount of chelating agent,
      SDS:CTAB mole ratio, and solvent amounts were thoroughly optimized. Under the
      optimal experimental conditions, the calibration curve was linear in the range of
      0.3-6 MUg L-1 Bi (III) with a limit of detection (LOD) of 0.16 MUg L-1 (S/N = 3).
      The relative standard deviations (RSD) of determination were obtained to be 5.1
      and 6.2 % for 1 and 3 MUg L-1 of Bi (III), respectively. The developed method was
      successfully applied as a sensitive and accurate technique for determination of
      bismuth ion in human blood serum, hair samples, and a certified reference
      material.

PMID- 27699650
TI  - Integrated in vitro approaches to assess the bioaccessibility and bioavailability
      of silicon-biofortified leafy vegetables and preliminary effects on bone.
AB  - Food industries are increasingly oriented toward new foods to improve nutritional
      status and/or to combat nutritional deficiency diseases. In this context, silicon
      biofortification could be an innovative tool for obtaining new foods with
      possible positive effects on bone mineralization. In this paper, an alternative
      and quick in vitro approach was applied in order to evaluate the potential health
      promoting effects of five silicon-biofortified leafy vegetables (tatsoi, mizuna,
      purslane, Swiss chard and chicory) on bone mineralization compared with a
      commercial silicon supplement. The silicon bioaccessibility and bioavailability
      of the five leafy vegetables (biofortified or not) and of the supplement were
      assessed by applying a protocol consisting of in vitro gastrointestinal digestion
      coupled with a Caco-2 cell model. Silicon bioaccessibility ranged from 0.89 to
      8.18 mg/L and bioavailability ranged from 111 to 206 MUg/L of Si for both
      vegetables and supplement. Furthermore, the bioavailable fractions were tested on
      a human osteoblast cell model following the expression of type 1 collagen and
      alkaline phosphatase. The results obtained highlighted that the bioavailable
      fraction of biofortified purslane and Swiss chard improved the expression of both
      osteoblast markers compared with the supplement and other vegetables. These
      results underline the potentially beneficial effect of biofortified leafy
      vegetables and also indicate the usefulness of in vitro approaches for selecting
      the best vegetable with positive bone effects for further in vivo research.

PMID- 27699651
TI  - Expression analysis of the endogenous Zscan4 locus and its coding proteins in
      mouse ES cells and preimplantation embryos.
AB  - Mouse Zinc finger and SCAN domain containing 4 (Zscan4) is encoded in multiple
      copies of Zscan4 genes, which are expressed in late two-cell stage
      preimplantation embryos and in 1-5% of the embryonic stem (ES) cell population at
      a given time. Due to the highly identical nucleotide sequences of multiple copies
      of Zscan4 paralogs and pseudogenes in the mouse Zscan4 genomic cluster, previous
      analyses have been done using exogenous transgenes under the regulation of
      Zscan4c promoter. In this manuscript, we generated knock-in mouse ES cell lines
      and mouse lines, in which the expression of endogenous Zscan4c, one of the Zscan4
      genes, can be specifically monitored with a green fluorescent protein variant,
      Emerald. Interestingly, we found that only ~30% of Zscan4-immunopositive ES cells
      were Emerald positive, suggesting that even when the Zscan4 locus is active, not
      all Zscan4 genes are expressed synchronously. We also carried out mass
      spectrometry of protein complexes associated with endogenous Zscan4 proteins.
      Taken together, our genetic engineering at an endogenous Zscan4c gene provides
      the first clue for the expression and function of each gene copy of Zscan4 locus
      in a physiological context.

PMID- 27699652
TI  - Insulin-like growth factor 1 regulation of proliferation and differentiation of
      Xenopus laevis myogenic cells in vitro.
AB  - To understand the mechanism of muscle remodeling during Xenopus laevis
      metamorphosis, we examined the in vitro effect of insulin-like growth factor 1
      (IGF-1) on growth and differentiation of three different-fate myogenic cell
      populations: tadpole tail, tadpole dorsal, and young adult leg muscle. IGF-1
      promoted growth and differentiation of both tail and leg myogenic cells only
      under conditions where these cells could proliferate. Inhibition of cell
      proliferation by DNA synthesis inhibitor cytosine arabinoside completely canceled
      the IGF-1's cell differentiation promotion, suggesting the possibility that IGF
      1's differentiation-promotion effect is an indirect effect via IGF-1's cell
      proliferation promotion. IGF-1 promoted differentiation dose dependently with
      maximum effect at 100-500 ng/ml. RT-PCR analysis revealed the upregulation (11
      fold) of ifg1 mRNA expression in developing limbs, suggesting that IGF-1 plays a
      role in promoting muscle differentiation during limb development. The combined
      effect of triiodo-L-thyronine (T3) and IGF-1 was also examined. In adult leg
      cells, IGF-1 promoted growth and differentiation irrespective of the presence of
      T3. In larval tail cells, cell count was 76% lower in the presence of T3, and IGF
      1 did not promote proliferation and differentiation in T3-containing medium. In
      larval dorsal cells, cell count was also lower in the presence of T3, but IGF-1
      enhanced proliferation and differentiation in T3-containing medium. This result
      is likely due to the presence among dorsal cells of both adult and larval types
      (1:1). Thus, IGF-1 affects only adult-type myogenic cells in the presence of T3
      and helps accelerate dorsal muscle remodeling during metamorphosis.

PMID- 27699653
TI  - Zscan4 is expressed specifically during late meiotic prophase in both
      spermatogenesis and oogenesis.
AB  - Mouse zinc finger and SCAN domain containing 4 (Zscan4) proteins, which are
      encoded by multiple copies of Zscan4 genes, are expressed specifically in
      preimplantation embryos in vivo and embryonic stem (ES) cells in vitro. However,
      the expression patterns of mouse Zscan4 in vivo have been largely elusive. Here,
      we show that Zscan4 proteins are expressed in adult ovaries and testes. In
      ovaries, Zscan4 proteins were detected in germinal vesicle (GV) stage oocytes in
      antral follicles, indicating that Zscan4 genes are activated during the
      diplotene/dictyate stage in meiotic prophase I. Remarkably, Zscan4 showed
      different spatial localization patterns between two distinct GV oocytes, which
      can be distinguished by global chromatin organization-surrounded nucleolus (SN)
      and non-surrounded nucleolus (NSN). These spatiotemporal differences in Zscan4
      localizations correlated with the transition of RNA polymerase II-mediated
      transcriptional status during GV oocyte maturation. In testes, Zscan4 proteins
      were detected in spermatocytes at late pachytene/diplotene stages and in Sertoli
      cells. These results suggest that Zscan4 may play critical roles during late
      meiotic prophase in both males and females.

PMID- 27699655
TI  - Serum level of neopterin is not a marker of disease activity in treated
      rheumatoid arthritis patients.
AB  - Neopterin has been measured in many autoimmune diseases and was reported as a
      marker of cellular immunity activation in rheumatoid asthritis (RA). The aim of
      this work was to assess serum neopterin as a marker of disease activity in
      treated RA patients. We measured serum level of neopterin in 120 treated RA
      patients and 100 age- and sex-matched controls by high-performance liquid
      chromatography (HPLC) method, and disease activity score was calculated in all
      patients by DAS28-CRP score. Significantly higher levels of neopterin were
      observed in RA patients (11.46 +/- 3.56 nmol/L) compared to healthy controls
      (4.74 +/- 1.98 nmol/L), P < 0.0001. Significantly higher neopterin levels were
      observed among male RA patients [median (IQR), 13.44 (12.65-16.21)] than female
      RA patients [median (IQR), 11.86 (7.91-13.44)], P <0.0001. No significant
      correlations between neopterin and age, age of disease onset, disease duration,
      or any of the disease activity parameters were found. Moreover, no significant
      difference regarding neopterin levels in different disease activity phases was
      identified. Our results indicated that neopterin is a marker of RA but not a
      marker of disease activity in treated RA patients.

PMID- 27699654
TI  - In vitro reprogramming of rat bmMSCs into pancreatic endocrine-like cells.
AB  - Islet transplantation provides curative treatments to patients with type 1
      diabetes, but donor shortage restricts the broad use of this therapy. Thus,
      generation of alternative transplantable cell sources is intensively investigated
      worldwide. We previously showed that bone marrow-derived mesenchymal stem cells
      (bmMSCs) can be reprogrammed to pancreatic-like cells through simultaneously
      forced suppression of Rest/Nrsf (repressor element-1 silencing transcription
      factor/neuronal restrictive silencing factor) and Shh (sonic hedgehog) and
      activation of Pdx1 (pancreas and duodenal transcription factor 1). We here aimed
      to reprogram bmMSCs further along the developmental pathway towards the islet
      lineages by improving our previous strategy and by overexpression of Ngn3
      (neurogenin 3) and NeuroD1 (neurogenic differentiation 1), critical regulators of
      the development of endocrine pancreas. We showed that compared to the previous
      protocol, the overexpression of only Pdx1 and Ngn3 reprogrammed bmMSCs into cells
      with more characteristics of islet endocrine lineages verified with bioinformatic
      analyses of our RNA-Seq datasets. These analyses indicated 2325 differentially
      expressed genes including those involved in the pancreas and islet development.
      We validated with qRT-PCR analysis selective genes identified from the RNA-Seq
      datasets. Thus, we reprogrammed bmMSCs into islet endocrine-like cells and
      advanced the endeavor to generate surrogate functional insulin-secreting cells.

PMID- 27699656
TI  - Dichotomous versus semi-quantitative scoring of ultrasound joint inflammation in
      rheumatoid arthritis using novel individualized joint selection methods.
AB  - The aim of the study is to compare the responsiveness of two joint inflammation
      scoring systems (dichotomous scoring (DS) versus semi-quantitative scoring (SQS))
      using novel individualized ultrasound joint selection methods and existing
      ultrasound joint selection methods. Responsiveness measured by the standardized
      response means (SRMs) using the DS and the SQS system (for both the novel and
      existing ultrasound joint selection methods) was derived using the baseline and
      the 3-month total inflammatory scores from 20 rheumatoid arthritis patients. The
      relative SRM gain ratios (SRM-Gains) for both scoring system (DS and SQS)
      comparing the novel to the existing methods were computed. Both scoring systems
      (DS and SQS) demonstrated substantial SRM-Gains (ranged from 3.31 to 5.67 for the
      DS system and ranged from 1.82 to 3.26 for the SQS system). The SRMs using the
      novel methods ranged from 0.94 to 1.36 for the DS system and ranged from 0.89 to
      1.11 for the SQS system. The SRMs using the existing methods ranged from 0.24 to
      0.32 for the DS system and ranged from 0.34 to 0.49 for the SQS system. The DS
      system appears to achieve high responsiveness comparable to SQS for the novel
      individualized ultrasound joint selection methods.

PMID- 27699657
TI  - Efficacy of combination DMARD therapy vs. hydroxychloroquine monotherapy in
      chronic persistent chikungunya arthritis: a 24-week randomized controlled open
      label study.
AB  - In a proportion of patients, chikungunya arthritis (CA) might run into a chronic
      persistent phase. The treatment for this phase is not very clear. In this
      randomized parallel group open label study of 24 weeks duration, we evaluated the
      efficacy of DMARD combination in persistent CA. Consecutive 139 patients with
      persistent CA (persistent arthritis for >1 year after the chikungunya fever
      either in 2008 or 2009 fulfilling epidemiological criteria for CA) were screened.
      Of these patients who were already taking hydroxychloroquine (HCQ) and had active
      arthritis were randomized to receive either fixed-dose combination therapy
      (methotrexate 15 mg/day, sulfasalazine 1 g/day, and HCQ 400 mg/day) or continue
      with HCQ 400 mg/day (dose optimized) monotherapy. Both groups received oral
      prednisolone up to 6 weeks. Assessments at every 4 weeks were carried out for
      primary efficacy (disease activity score; DAS ESR 28) and secondary efficacies,
      HAQ-Indian version and pain VAS100mm. Seventy-two patients were randomized (37
      combination therapy, 35 monotherapy). Both groups were well matched in all
      respects. At 24 weeks, the combination therapy group showed significant
      improvement in both disease activity (mean +/- SD DAS28; 3.39 +/- 0.87 vs. 4.74
      +/- 0.65, p < 0.0001) and disability (mean +/- SD HAQ; 1.4 +/- 0.31 vs. 1.88 +/-
      0.47, p < 0.0001). At the study end, pain VAS was significantly less in the
      combination therapy group (46 +/- 6.13 vs. 60.8 +/- 11.6, p < 0.0001). Three
      patients withdrew from the combination group (inefficacy; 2, adverse event; 1)
      and seven from monotherapy (inefficacy; 7). This study provide evidence that for
      chronic persistent CA combination DMARD therapy with methotrexate, sulfasalazine
      and HCQ is superior to monotherapy with HCQ.

PMID- 27699658
TI  - Uptake, translocation, and metabolism of hydroxylated and methoxylated
      polychlorinated biphenyls in maize, wheat, and rice.
AB  - Hydroxylated polychlorinated biphenyls (OH-PCBs) have been found in the
      environment with high toxicity. Recently, methoxylated polychlorinated biphenyls
      (MeO-PCBs) were identified as new pollutants and detected in sewage sludge. This
      study presents a detailed investigation on the uptake, translocation, and
      metabolism of OH-PCBs and MeO-PCBs in typical crops including maize, wheat, and
      rice. The interconversion between OH-PCBs and MeO-PCBs were observed.
      Demethylation of MeO-PCBs was favored over methylation of OH-PCBs. The
      metabolites were mainly generated in the roots and then translocated to the
      shoots. Analog-specific differences showed that the accumulation amounts of MeO
      PCBs were higher than those of OH-PCBs in the crops. The translocation abilities
      followed this order: 3'-OH-CB-65 > 4'-OH-CB-101 > 3'-MeO-CB-65 > 4'-MeO-CB-101.
      The conversion rates were generally higher for 4'-OH-CB-101 than 3'-OH-CB-65 and
      higher for 4'-MeO-CB-101 than 3'-MeO-CB-65. Interspecies variability among the
      crops was also observed. The amounts of metabolites and acropetal translocation
      inside the plants were the greatest for maize. However, the concentration of
      compounds normalized by the mass of corresponding plant tissue was highest in
      wheat. These findings provide valuable information for a better understanding of
      the phytoaccumulation and phytotransformation of OH-PCBs and MeO-PCBs.

PMID- 27699659
TI  - Biosurfactant-enhanced removal of o,p-dichlorobenzene from contaminated soil.
AB  - Surfactant-enhanced remediation is less applicable for the treatment of
      dichlorobenzene (DCB)-contaminated soil. In this study, water solubility
      enhancements of o-dichlorobenzene (o-DCB) and p-dichlorobenzene (p-DCB) by
      micellar solutions of biosurfactants (saponin, alkyl polyglycoside) and
      chemically synthetic surfactant (Tween 80) were measured and compared.
      Solubilities of o,p-DCB in water were greatly enhanced in a linear fashion by
      each of Tween 80, saponin, and alkyl polyglycoside. Solubility enhancement
      efficiencies of surfactants followed the order of Tween 80 > saponin > alkyl
      polyglycoside. However, the ex situ soil washing experiment demonstrated the
      opposite result. The removal efficiency of o,p-DCB by biosurfactant saponin and
      alkyl polyglycoside was higher than that of chemically synthetic surfactant Tween
      80 in contaminated soil. This difference may be due to the different adsorption
      behaviors of the surfactants onto soil. In addition, elution kinetics for o,p-DCB
      were relatively fast, with apparent elution equilibrium reached within 360 min,
      and can be described by a pseudo first-order kinetic equation. The elution
      process of o,p-DCB in soil-aqueous systems obeyed four-parameter biphasic first
      order kinetic model including rapid and slow phases. The results confirmed
      potential application of saponin and alkyl polyglycoside in elution solution for
      enhanced remediation of DCB-contaminated soil.

PMID- 27699661
TI  - Response to the letter to the editor 'discussion on: Dahab AA, Elhag DEA, Ahmed
      AB, Al-Obaid HA. Determination of elemental toxicity migration limits,
      bioaccessibility and risk assessment of essential childcare products'.

PMID- 27699660
TI  - Occurrence, fate, and risk assessment of selected endocrine disrupting chemicals
      in wastewater treatment plants and receiving river of Shanghai, China.
AB  - The occurrence and fate of five endocrine disrupting chemicals (EDCs), including
      nonylphenol (NP), 4-tert-octylphenol (4-t-OP), 4-tert-butylphenol (4-t-BP),
      bisphenol A (BPA) and norethindrone (NET) was investigated in four wastewater
      treatment plants (WWTPs) and receiving river (Suzhou River and Yangtze River) of
      Shanghai. Selected EDCs in WWTPs influents ranged from 1.02 to 3560 ng L-1, which
      dominated by NP and BPA. Target compounds detected in effluents were from N.D. to
      1136 ng L-1, with NP as most prevalent. The removal rates of target compounds
      varied from negative of NET to 99 % of BPA. Except of NET, efficiently removal
      rates (>70 %) were observed in WWTPs. Biological treatment was the major removal
      stage of selected EDCs in WWTPs. Furthermore, the selected EDCs were detected
      from N.D. to 424 ng L-1 in receiving river. The correlation analysis suggested
      EDCs pollution in receiving river might be mainly contributed by WWTPs effluents.
      The risk quotient of NP (RQ > 1) was higher than any other pollutants, indicating
      its relatively higher potential risk for the aquatic organism. These results will
      provide significant background data to future EDCs pollution control and
      management in Shanghai, China.

PMID- 27699662
TI  - Imaging the implant-soft tissue interactions in total knee arthroplasty.
AB  - BACKGROUND: In Total Knee Arthroplasty (TKA), residual pain may be secondary to
      soft tissue impingements, which are difficult to visualize around chromium-cobalt
      implants using medical imaging, so their interactions remain poorly understood.
      The goal of this work was to establish a protocol for in-vitro imaging of the
      soft tissues around TKA, usable during throughout the range of motion (ROM).
      METHODS: The full size range of a commercially available TKA prosthesis was
      manufactured by 3D-printing in non-magnetic and non-radiopaque polymer and
      implanted in 12 cadaveric knees. The relations between these implants and the
      soft tissues (Popliteus tendon, Medial and Lateral Collateral Ligament, Patellar
      and Quadriceps tendons) were analyzed, using MRI (5 embalmed specimens) and CT
      scans after injection of the tissues with barium-sulfate (3 embalmed and 4 fresh
      frozen specimens). RESULTS: Both MRI and CT scans enabled good identification of
      the soft tissues before TKA implantation. MRI produced minimal loss in signal and
      contrast, and neither the low temperature nor the embalming fluids compromised
      image quality. CT scans were more precise after TKA implantation, particularly
      the borders of the implant and the differentiation of soft tissues. Full ROM
      investigation, manual segmentation and three-dimensional reconstructions were
      possible only with the CT scan. CONCLUSION: The experimental approach described
      in this study was successful in visualizing the interactions between the soft
      tissue and the implants before and after TKA and during the full ROM. The
      coordinate system allows to localize precisely the different anatomic structures
      and to quantify any change due to prosthetic implantation.

PMID- 27699663
TI  - Impact of point mutation P29S in RAC1 on tumorigenesis.
AB  - A point mutation (P29S) in the RAS-related C3 botulinum toxin substrate 1 (RAC1)
      was considered to be a trigger for melanoma, a form of skin cancer with highest
      mortality rate. In this study, we have investigated the pathogenic role of P29S
      based on the conformational behavior of RAC1 protein toward guanosine
      triphosphate (GTP). Molecular interaction, molecular dynamics trajectory analysis
      (RMSD, RMSF, Rg, SASA, DSSP, and PCA), and shape analysis of binding pocket were
      performed to analyze the interaction energy and the dynamic behavior of native
      and mutant RAC1 at the atomic level. Due to this mutation, the RAC1 switch I
      region acquired more flexibility and, to compensate it, the switch II region
      becomes rigid in their conformational space, as a result of which the interaction
      energy of the protein for GTP increased. The overall results strongly implied
      that the changes in atomic conformation of the switch I and II regions in mutant
      RAC1 protein were a significant reason for its malignant transformation and
      tumorigenesis. We raised the opportunity for researchers to design possible
      therapeutic molecule by considering our findings.

PMID- 27699664
TI  - RIP1 upregulation promoted tumor progression by activating AKT/Bcl-2/BAX
      signaling and predicted poor postsurgical prognosis in HCC.
AB  - Although growing body of evidences have identified a critical role for receptor
      interacting protein kinase 1 (RIP1) in mediating cell death signaling, its
      possible contribution to hepatocellular carcinoma (HCC) progression remains
      unclear. Here, we displayed that expression of RIP1 was significantly upregulated
      in HCC tissues than in adjacent liver tissues from 81.9 % HCC patients (P <
      0.001) by immunohistochemistry (IHC) staining. Overexpression of RIP1 was found
      positively associated with HBV infection, advanced TNM staging, portal vein
      invasion, and intrahepatic metastases. Kaplan-Meier curve analysis indicated that
      patients with higher RIP1 expression in HCC tissues suffered from unfavorable
      postsurgical survival. Higher RIP1 expression in HCC tissues was also confirmed
      to be an independent poor prognostic predictor. Knockdown of RIP1 resulted in
      suppression of cell viability and proliferation and induced cell apoptosis in
      MHCC97h cells. Nevertheless, enforced expression of RIP1 promoted cell viability
      and proliferation of Huh7 cells and inhibited cell apoptosis. Mechanistic studies
      revealed that RIP1 exerted its function on HCC progression via activating AKT/Bcl
      2/BAX signaling. In conclusion, our results provided the evidence of RIP1
      overexpression in HCC, and RIP1 could be a novel predictive factor of unfavorable
      prognosis in HCC patients. Activation of AKT/Bcl-2/BAX signaling contributed to
      RIP1 promoting HCC progression.

PMID- 27699666
TI  - High-Performance Liquid Chromatography Analysis of CYP2C8-Catalyzed Paclitaxel
      6alpha-Hydroxylation.
AB  - Paclitaxel (Taxol) is a naturally occurring member of the taxane family of
      antitumor drugs, which act by stabilizing microtubules. Paclitaxel is inactivated
      in human liver by a cytochrome P450 (P450)-catalyzed 6alpha-hydroxylation
      reaction. A reverse-phase, high-performance liquid chromatographic assay is
      described for the analysis of paclitaxel 6alpha-hydroxylation catalyzed by human
      liver microsomes or cDNA-expressed P450 enzyme CYP2C8. Analytical separations are
      achieved using a C18 column with a linear gradient of 10-100% methanol, with
      detection at 230 nm. This method is applicable to enzymatic studies for
      determination of CYP2C8-catalyzed paclitaxel 6alpha-hydroxylation activity.

PMID- 27699667
TI  - Thin-Layer Chromatography Analysis of Human CYP3A-Catalyzed Testosterone 6beta
      Hydroxylation.
AB  - Testosterone and other steroid hormones have been studied as prototypic examples
      of endogenous substrates for hepatic cytochrome P450 (P450) enzymes. CYP3A
      enzymes from various species, including human, metabolize testosterone by a 6beta
      hydroxylation reaction, which is unique to this P450 subfamily. A thin-layer
      chromatographic method is described for the determination of 6beta
      hydroxytestosterone formed enzymatically by incubation of [14C]-testosterone with
      cDNA-expressed CYP3A enzymes or liver microsomes. 14C-labeled enzymatic products
      are applied to silica gel thin-layer plates, which are developed sequentially
      with methylene chloride:acetone (80:20) followed by chloroform, ethyl acetate,
      and absolute ethanol (80:20:14). Metabolite quantification is performed by
      autoradiography and liquid scintillation counting. This method is applicable to
      enzymatic studies for the determination of CYP3A-dependent testosterone 6beta-
      hydroxylation activity in both human and animal liver microsomes.

PMID- 27699665
TI  - miR-222 induces Adriamycin resistance in breast cancer through PTEN/Akt/p27kip1
      pathway.
AB  - The high resistant rate of Adriamycin (Adr) is associated with a poor prognosis
      of breast cancer in women worldwide. Since miR-222 might contribute to
      chemoresistance in many cancer types, in this study, we aimed to investigate its
      efficacy in breast cancer through PTEN/Akt/p27 kip1 pathway. Firstly, in vivo, we
      verified that miR-222 was upregulated in chemoresistant tissues after surgery
      compared with the paired preneoadjuvant samples of 21 breast cancer patients.
      Then, human breast cancer Adr-resistant cell line (MCF-7/Adr) was constructed to
      validate the pathway from the parental sensitive cell line (MCF-7/S). MCF-7/Adr
      and MCF-7/S were transfected with miR-222 mimics, miR-222 inhibitors, or their
      negative controls, respectively. The results showed that inhibition of miR-222 in
      MCF-7/Adr significantly increased the expressions of PTEN and p27 kip1 and
      decreased phospho-Akt (p-Akt) both in mRNA and protein levels (p < 0.05) by using
      quantitative real-time PCR (qRT-PCR) and western blot. MTT and flow cytometry
      suggested that lower expressed miR-222 enhanced apoptosis and decreased the IC50
      of MCF-7/Adr cells. Additionally, immunofluorescence demonstrated that the
      subcellular location of p27 kip1 was dislocated resulting from the alteration of
      miR-222. Conversely, in MCF-7/S transfected with miR-222 mimics, upregulation of
      miR-222 is associated with decreasing PTEN and p27 kip1 and increasing Akt
      accompanied by less apoptosis and higher IC50. Importantly, Adr resistance
      induced by miR-222 overexpression through PTEN/Akt/p27 was completely blocked by
      LY294002, an Akt inhibitor. Taken together, these data firstly elucidated that
      miR-222 could reduce the sensitivity of breast cancer cells to Adr through
      PTEN/Akt/p27 kip1 signaling pathway, which provided a potential target to
      increase the sensitivity to Adr in breast cancer treatment and further improved
      the prognosis of breast cancer patients.

PMID- 27699668
TI  - An Isocratic High-Performance Liquid Chromatography Assay for CYP7A1-Catalyzed
      Cholesterol 7alpha-Hydroxylation.
AB  - A normal-phase, isocratic high-performance liquid chromatography assay is
      described for cholesterol 7alpha-hydroxylation catalyzed by CYP7A1, which
      corresponds to the first and rate-limiting step in the conversion of cholesterol
      into bile acids. This method is based on the conversion of the primary cytochrome
      P450 metabolite, 7alpha-hydroxycholesterol, into 7alpha-hydroxy-4-cholesten-3-one
      in a reaction catalyzed by exogenous cholesterol oxidase, followed by
      chromatographic separation with monitoring at 254 nm. This technique is
      applicable to enzymatic studies for determination of cholesterol 7alpha-
      hydroxylation activity catalyzed by cDNA-expressed CYP7A1 and animal or human
      liver microsomes.

PMID- 27699669
TI  - The Human Cytochrome P450 Allele Nomenclature Committee Web Site : Submission
      Criteria, Procedures, and Objectives.
AB  - Interindividual variability in xenobiotic metabolism and drug response is
      extensive. Genetic factors are predicted to account for 15-30% of this
      variability in general, but for certain drugs the genetic factor is the major
      determinant for outcome of drug therapy. Of particular importance for drug
      metabolism, drug response, and adverse drug reactions are the cytochrome P450
      (CYP) enzymes, many of which are polymorphic. An essential basis for research and
      applications regarding interindividual variability in xenobiotic metabolism and
      toxicity by polymorphic CYPs is to have a common nomenclature for genetic
      variants and a system that allows researchers to be rapidly updated within the
      field. Since 1999 this has been achieved by the operation of the Human Cytochrome
      P450 Allele Nomenclature Committee Web site ( http://www.imm.ki.se/CYPalleles/ ),
      where novel allelic variants are published after peer review. Currently, this Web
      site covers the nomenclature for polymorphic alleles of 22 CYP isoforms including
      more than 200 functionally different variants. Each CYP has its own Web page,
      which lists the alleles with their nucleotide changes, their functional
      consequences, and links to publications where the allele has been identified and
      characterized. The CYP allele Web site offers a rapid on-line publication of new
      alleles, provides an overview of peer-reviewed data, and serves as a form of
      quality control on research on new alleles.

PMID- 27699670
TI  - Rat Hepatocyte Cultures : Conventional Monolayer and Cocultures With Rat Liver
      Epithelial Cells.
AB  - Primary cultures of hepatocytes are useful tools for both short- and long-term
      pharmacotoxicological research. Under conventional conditions, isolated
      hepatocytes form a monolayer and survive for about 1 wk but lose some liver
      specific functions, including xenobiotic biotransformation. In comparison with
      the conventional monolayer culture model, cocultures with rat liver epithelial
      cells (RLECs) have an extended life-span and better maintain their drug
      metabolizing capacity, owing to the presence of cell-cell interactions. In this
      chapter, techniques for setting up conventional monolayer cultures and cocultures
      of hepatocytes with RLECs (including isolation, culture, and cryopreservation of
      RLECs) are described in detail. In addition, comments derived from our own
      experience are given for successfully culturing primary hepatocytes.

PMID- 27699671
TI  - Rat Hepatocyte Cultures : Collagen Gel Sandwich and Immobilization Cultures.
AB  - Mimicking the in vivo microenvironment is one of the current strategies to
      maintain liver-specific functionality in primary cultured hepatocytes for long
      periods. Freshly isolated hepatocytes entrapped in collagen gel type I (collagen
      gel immobilization culture) or sandwiched between two layers of hydrated collagen
      type I (collagen gel sandwich culture) are known to display liver-specific
      functions (e.g., biotransformation capacity) for more than 6 wk. We describe how
      to set up both types of organotypical hepatocyte culture systems. Besides a
      detailed protocol, we give some practical tips, taken from our own experience
      with long-term hepatocyte culture.

PMID- 27699672
TI  - Transfection of Primary Cultures of Rat Hepatocytes.
AB  - Five different transfection reagents-calcium phosphate, TransFastTM Transfection
      Reagent, SuperfectTM Transfection Reagent, EffecteneTM Transfection Reagent, and
      TfxTM-20-were compared for their ability to effectively transfect primary
      cultures of male rat hepatocytes. Hepatocytes were isolated by the collagenase
      perfusion method and then cultured on Matrigel-coated plates for 24 h before
      transfection. The cells were transfected with either pGL3-Control or pGL3-Basic
      plasmids. The efficiency of transfection of each reagent was monitored using the
      dual luciferase reporter gene assay system. Superfect Transfection Reagent,
      Effectene Transfection Reagent and Tfx-20 were the most effective for the
      transfection of primary hepatocytes and gave comparable transfection
      efficiencies. Calcium phosphate was found to be the least effective transfection
      reagent and gave the most variable transfection results. Tfx-20 gave the least
      variable transfection results when different hepatocyte preparations were
      compared.

PMID- 27699673
TI  - Determination of Cellular Localization of Expression of Flavin-Containing
      Monooxygenase Genes in Mouse Tissues by In Situ Hybridization.
AB  - Methods are described for the cellular localization of expression of flavin
      containing monooxygenase (FMO) genes in various mouse tissues by in situ
      hybridization. These include the production of digoxigenin (DIG)-labeled
      antisense and sense RNA probes by transcription from FMO cDNA templates, the
      preparation of paraffin wax-embedded and cryostat tissue sections, the
      hybridization of RNA probes to tissue sections, and the specific detection of
      hybridized probes using an antibody to DIG.

PMID- 27699674
TI  - Deletion of Genes From the Mouse Genome Using Cre/loxP Technology.
AB  - The steps required to delete genes from the mouse genome are illustrated by
      showing how a cluster of three flavin-containing monooxygenase (Fmo) genes (Fmo1,
      Fmo2, and Fmo4) were deleted from mouse chromosome 1. Such large deletions are
      accomplished using loxP/Cre recombinase technology. Genomic clones corresponding
      to the genes to be deleted are first isolated, and then appropriate genomic
      fragments are cloned into vectors containing a loxP site. This produces targeting
      vectors, which are electroporated into mouse embryonic stem (ES) cells to allow a
      homologous recombination event to take place between the mouse genomic fragment,
      present within the vector, and the homologous sequences in the ES cell genome.
      Screening of ES cells for recombinants in which loxP sites have been inserted on
      either side of the gene cluster to be deleted is described. Recombination by Cre
      recombinase to produce ES cell lines carrying the deletion on chromosome 1 is
      also described.

PMID- 27699675
TI  - Characterization of Targeted Mouse Embryonic Stem Cell Chromosomes : Karyotyping
      and Fluorescence In Situ Hybridization of Metaphase Spreads.
AB  - The manipulation of genes in mouse embryonic stem (ES) cells can result in
      chromosome abnormalities. This chapter describes methods for karyotyping of the
      manipulated ES cell line before injection into blastocysts and the use of
      fluorescence in situ hybridization to confirm the deletion of a targeted gene.
      The method is illustrated by describing how an ES cell line targeted for the
      deletion of Fmo genes was characterized.

PMID- 27699676
TI  - Microinjection of Targeted Embryonic Stem Cells and Establishment of Knockout
      Mouse Lines for Fmo Genes.
AB  - Methods are described for the injection of mouse embryonic stem cells, in which
      Fmo genes have been targeted to disrupt gene function, into 3.5-d-old blastocysts
      and the implantation of these into foster mothers. Successful injection and
      implantation of blastocysts will produce mice of mixed coat color (the chimera).
      Also described are methods to establish the success of blastocyst injection and
      implantation of germ-line transmission of the knockout (KO) mutation. Breeding
      strategies to produce congenic and isogenic KO mouse lines are outlined. Simple
      methods for the isolation of tail DNA, the tagging of mice, and record keeping of
      the line are also given.

PMID- 27699677
TI  - Purification of Cytochromes P450 : Products of Bacterial Recombinant Expression
      Systems.
AB  - A general procedure for the solubilization of cytochrome P450 (P450) from
      bacterial membranes specifically for a human P450 expressed heterologously in the
      host Escherichia coli is described. The example involves the use of a P450 (3A4)
      with a C-terminal oligohistidine tag and includes sequential DEAE and metal
      affinity chromatography.

PMID- 27699678
TI  - Expression of Recombinant Flavin-Containing Monooxygenases in a
      Baculovirus/Insect Cell System.
AB  - The baculovirus/insect cell heterologous expression system provides an important
      tool for investigating the catalytic activity of individual drug-metabolizing
      enzymes toward a particular substrate. In this chapter we describe a
      baculovirus/insect cell system that we have used for the expression of human and
      mouse flavin-containing monooxygenases. Methods are described for the generation
      of recombinant baculoviral DNAs, via both site-specific transposition in
      Escherichia coli and site-specific recombination in vitro; adaptation of
      Spodoptera frugiperda (Sf) 9 cells to shaking culture and to serum-free medium;
      cryopreservation and transfection of Sf9 cells; amplification of baculovirus and
      determination of viral titer; analysis of baculoviral DNA; and expression and
      analysis of recombinant proteins.

PMID- 27699679
TI  - Catalytic Assays for Human Cytochrome P450 : An Introduction.
AB  - Cytochrome P450 (P450) is a superfamily of individual monooxygenase enzymes that
      metabolize structurally diverse xenochemicals, including many clinically useful
      drugs and foreign chemicals widespread in the environment. P450 substrates that
      can be used to selectively monitor individual P450 enzymes or P450 subfamilies
      have been identified through studies using P450 enzyme-selective inhibitory
      antibodies and chemical inhibitors in conjunction with experiments utilizing
      individual cDNA-expressed P450 enzymes. This chapter describes P450 form
      selective substrates that can be used to monitor the activities of human P450
      enzymes CYP1A, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1,
      CYP3A, CYP4A11, and CYP7A1. Cautions that need to be exercised when using these
      substrates to probe for individual P450 activities in human liver and other
      tissues are discussed.

PMID- 27699680
TI  - Lateral and medial prefrontal contributions to emotion generation by semantic
      elaboration during episodic encoding.
AB  - Memories for emotion-laden stimuli are remembered more accurately than those for
      neutral stimuli. Although this enhancement reflects stimulus-driven modulation of
      memory by emotions, functional neuroimaging evidence of the interacting
      mechanisms between emotions generated by intentional processes, such as semantic
      elaboration, and memory is scarce. The present fMRI study investigated how
      encoding-related activation is modulated by emotions generated during the process
      of semantic elaboration. During encoding with fMRI, healthy young adults viewed
      neutral (target) pictures either passively or with semantic elaboration. In
      semantic elaboration, participants imagined background stories related to the
      pictures. Encoding trials with semantic elaboration were subdivided into
      conditions in which participants imagined negative, positive, or neutral stories.
      One week later, memories for target pictures were tested. In behavioral results,
      memories for target pictures were significantly enhanced by semantic elaboration,
      compared to passive viewing, and the memory enhancement was more remarkable when
      negative or positive stories were imagined. fMRI results demonstrated that
      activations in the left inferior frontal gyrus and dorsal medial prefrontal
      cortex (dmPFC) were greater during the encoding of target pictures with semantic
      elaboration than those with passive viewing, and that these activations further
      increased during encoding with semantic elaboration of emotional stories than of
      neutral stories. Functional connectivity between the left inferior frontal gyrus
      and dmPFC/hippocampus during encoding significantly predicted retrieval
      accuracies of memories encoded with self-generated emotional stories. These
      findings suggest that networks including the left inferior frontal region, dmPFC,
      and hippocampus could contribute to the modulation of memories encoded with the
      emotion generation.

PMID- 27699682
TI  - Development of SmokeFree Baby: a smoking cessation smartphone app for pregnant
      smokers.
AB  - Pregnant smokers may benefit from digital smoking cessation interventions, but
      few have been designed for this population. The aim was to transparently report
      the development of a smartphone app designed to aid smoking cessation during
      pregnancy. The development of a smartphone app ('SmokeFree Baby') to help
      pregnant women stop smoking was guided by frameworks for developing complex
      interventions, including the Medical Research Council (MRC), Multiphase
      Optimization Strategy (MOST) and Behaviour Change Wheel (BCW). Two integrative
      behaviour change theories provided the theoretical base. Evidence from the
      scientific literature and behaviour change techniques (BCTs) from the BCT
      Taxonomy v1 informed the intervention content. The app was developed around five
      core modules, each with a distinct intervention target (identity change, stress
      management, health information, promoting use of face-to-face support and
      behavioural substitution) and available in a 'control' or 'full' version.
      SmokeFree Baby has been developed as part of a multiphase intervention
      optimization to identify the optimum combination of intervention components to
      include in smartphone apps to help pregnant smokers stop smoking.

PMID- 27699681
TI  - Electrophysiological correlates of emotional face processing after mild traumatic
      brain injury in preschool children.
AB  - Evidence suggests that social skills are affected by childhood mild traumatic
      brain injury (mTBI), but the neural and affective substrates of these
      difficulties are still underexplored. In particular, nothing is known about
      consequences on the perception of emotional facial expressions, despite its
      critical role in social interactions and the importance of the preschool period
      in the development of this ability. This study thus aimed to investigate the
      electrophysiological correlates of emotional facial expressions processing after
      early mTBI. To this end, 18 preschool children (mean age 53 +/- 8 months) who
      sustained mTBI and 15 matched healthy controls (mean age 55 +/- 11 months) were
      presented with pictures of faces expressing anger, happiness, or no emotion
      (neutral) while event-related potentials (ERP) were recorded. The main results
      revealed that P1 amplitude was higher for happy faces than for angry faces, and
      that N170 latency was shorter for emotional faces than for neutral faces in the
      control group only. These findings suggest that preschool children who sustain
      mTBI do not present the early emotional effects that are observed in healthy
      preschool children at visuospatial and visual expertise stages. This study
      provides new evidence regarding the consequences of childhood mTBI on
      socioemotional processing, by showing alterations of emotional facial expressions
      processing, an ability known to underlie social competence and appropriate social
      interactions.

PMID- 27699683
TI  - Physical activity for children in elementary schools: time for a rethink?
AB  - In spite of the well-known benefits of physical activity, the vast majority of
      children in North America do not meet current international guidelines for
      accumulating sufficient health-enhancing physical activity. Indeed, despite
      considerable attention to this population health crisis, the current prevalence
      of inactivity, along with its concomitant health consequences, shows little sign
      of abating. In this paper, we identify acknowledged barriers to wide scale
      physical activity adoption and maintenance at the population level among children
      and propose a viable tripartite framework (albeit one that would require
      political support) that we hope will provide the basis for debate and
      implementation. We emphasize that each of these considerations, in isolation,
      would be insufficient to substantively address the problem, but when combined
      would ensure that all elementary school children (without any medical
      contraindication) are sufficiently active, rather than the minority of this
      population.

PMID- 27699685
TI  - Development of the Emotion Dysregulation Inventory: A PROMIS(r)ing Method for
      Creating Sensitive and Unbiased Questionnaires for Autism Spectrum Disorder.
AB  - The lack of sensitive measures suitable for use across the range of functioning
      in autism spectrum disorder (ASD) is a barrier to treatment development and
      monitoring. The Emotion Dysregulation Inventory (EDI) is a caregiver-report
      questionnaire designed to capture emotional distress and problems with emotion
      regulation in both minimally verbal and verbal individuals. The first two phases
      of the EDI's development are described, including: (1) utilizing methods from the
      Patient-Reported Outcomes Measurement Information System (PROMIS(r)) project to
      develop the item pool and response options; and (2) assessment of the EDI in
      psychiatric inpatients with ASD. The results suggest that the EDI captures a wide
      range of emotion dysregulation, is sensitive to change, and is not biased by
      verbal or intellectual ability.

PMID- 27699684
TI  - Design and Cohort Characteristics of the Social Spectrum Study: A Multicenter
      Study of the Autism Spectrum Among Clinically Referred Children.
AB  - This paper provides an overview of the design and cohort characteristics of the
      Social Spectrum Study: a clinical cohort study that used a two-phase sampling
      design to identify children at risk for ASD. After screening 1281 children aged
      2.5-10 years who had been consecutively referred to one of six mental health
      services in the Netherlands, children who screened positive for ASD (n = 428) and
      a random selection of screen negatives (n = 240) were invited to participate in
      diagnostic assessments and questionnaires regarding the child, family and
      society. A 1-year follow-up was also conducted. Results from this study may
      contribute to knowledge of the identification and characterization of children
      with ASD, family processes, and the impact of ASD on the family and society.

PMID- 27699687
TI  - Detection of allergen sources in the homes of sensitized children.
AB  - OBJECTIVE: To identify the presence of environmental factors linked to the onset
      of allergies and asthma in the homes of children participating in an early
      detection program that were identified with sensitivity to common allergens in
      the region of Sonora, Mexico. METHODS: A walkthrough assessment was carried out
      in the homes of sensitized children; the research tools were the questionnaire
      and environmental checklist proposed by the Lowell Healthy Homes Program of the
      University of Massachusetts-Lowell. RESULTS: The results showed the presence of
      environmental allergen sources, to which most of the children in the study are
      sensitized, as well as the environmental conditions and habits that determine the
      quality of the indoor air of the households, were both related to triggering
      allergies and asthma in this population. A statistically significant association
      was found between the visual observation of dust inside homes and the sensitivity
      of children to dust mites. CONCLUSIONS: Dust found inside the home was the most
      relevant environmental factor related to positive cases of IgE in children. Early
      detection of allergies in children in the study and the methodology used in this
      investigation provided a useful framework for the design of plans and
      intervention alternatives in these homes to prevent the development of allergies
      and asthma panorama. These plans should be designed with a multidisciplinary
      approach to impact social, environmental and economic benefits in the family,
      improving the living conditions of the study population and contributing to the
      sustainable development goals of the United Nations for 2030.

PMID- 27699689
TI  - The distinctive characteristics of the hourly distribution of live births on
      specific days in Japan.
AB  - OBJECTIVES: Anomalous variations in live births on February 29/March 1, April
      1/April 2 and the days before the New Year holidays/New Year holidays have been
      reported in Japan. The distribution of live births was investigated on those days
      and whether or not such dates were selected due to obstetric intervention is
      discussed. METHODS: Using a method similar to the [Formula: see text]-R control
      chart, anomalous variations in the hourly number of live births were detected.
      The number of unusual births was estimated. RESULTS: The number of live births at
      13:00-16:59 hours was significantly higher from December 24 to 28 and
      significantly lower from December 29-January 3, February 29, and April 1,
      especially on weekdays. In hospitals, the increases from 9:00-12:59 and 13:00
      16:59 hours from December 24 to 27 were approximately 10 and 25 %, respectively,
      of the expected births for those times in the mid-1980s; thereafter, the rates
      were 30 and 35 %. After 2000, the child births at 13:00-16:59 hours on February
      29 and April 1 decreased by approximately 35 % in hospitals and clinics. The
      numbers of live births at 0:00-0:59 hours were significantly higher on March 1
      and April 2 until 2001. CONCLUSION: Anomalous variations at 0:00-0:59 hours may
      be associated with fictitious reporting on birth certificates. Anomalous
      variations from 13:00 to 16:59 hours on weekdays suggest that many individuals
      may avoid obstetric intervention on February 29 and April 1 and that the number
      of higher-risk deliveries may significantly increase in the daytime on the days
      before the New Year holidays due to obstetric intervention for institutional
      reasons.

PMID- 27699688
TI  - Evaluation of the Japanese Metabolic Syndrome Risk Score (JAMRISC): a newly
      developed questionnaire used as a screening tool for diagnosing metabolic
      syndrome and insulin resistance in Japan.
AB  - OBJECTIVES: To prevent the onset of lifestyle-related diseases associated with
      metabolic syndrome (MetS) in Japan, research into the development of a useful
      screening method is strongly desired. We developed a new screening questionnaire
      (JAMRISC) utilizing a logistic regression model and evaluated its ability to
      predict the development of MetS, type 2 diabetes and other lifestyle-related
      diseases in Japanese populace. METHODS: JAMRISC questionnaire was sent to 1,850
      individuals in Rumoi, a small city in Hokkaido. We received a total of 1,054
      valid responses. To maximize the target individuals accurately diagnosed with
      MetS, logistic regression analysis was used to generate a unique metabolic
      syndrome score calculation formula as taking into consideration the clinical
      relevance of each question item as individual coefficients. RESULTS: The results
      of our comparative research utilizing both JAMRISC and Finnish Diabetes Risk
      Score (FINDRISC) questionnaires revealed the usefulness of JAMRISC for its
      ability to detect risks for MetS, pre-MetS, diabetes, and pre-diabetes. Study of
      disease risk detection via JAMRISC questionnaire targeting the 4283 residents of
      Rumoi indicated a high detection rate for pre-MetS (98.8 %), MetS (94.2 %), pre
      diabetes (85.1 %) and type 2 diabetes (94.9 %). In addition, JAMRISC was useful
      not only as a MetS risk score test, but also as a screening tool for diagnosing
      insulin resistance. CONCLUSIONS: JAMRISC questionnaire is a useful instrument for
      the detection of early risk of not only MetS and type 2 diabetes but also insulin
      resistance.

PMID- 27699690
TI  - Prevalence, adverse health, and risk factors in association with sensory
      impairments: data from a prospective cohort study of older Japanese.
AB  - Sensory impairments, mainly of vision and hearing, are prevalent among the older
      adults, and are the leading causes of disability in people aged 60 years and
      above around the world. However, epidemiological data on sensory impairments
      (prevalence, association with adverse health outcomes, risk and preventive
      factors, etc.) in community-dwelling older people are sparse in Japan. Using data
      from the Kurabuchi Study, a community-based prospective cohort study of adults
      aged 65 years or older, the author and colleagues estimated the prevalence of
      sensory impairments in this population. Vision and hearing impairments were
      associated with adverse health outcomes, such as depressive symptoms, dependence
      in activities of daily living, and early death. In addition, antioxidants,
      sunlight exposure, hyperglycaemia, and nutritional status were identified as
      possible risk or preventive factors for vision and/or hearing impairments.
      Further research is needed into whether the maintenance or improvement of sensory
      functions contributes to the extension of disability-free life expectancy.

PMID- 27699691
TI  - Factors associated with illicit opioid use in methadone maintenance treatment
      clients in 5 Provinces, China.
AB  - OBJECTIVES: To investigate factors associated with illicit opioid use among
      methadone maintenance treatment (MMT) population. METHODS: Participants were
      recruited from Beijing (2 clinics), Shanghai (2 clinics), Guangdong (2 clinics),
      Chongqing (2 clinics) and Gansu (1 clinic) provinces. Information about heroin
      use and MMT was obtained from a self-reported questionnaire, illicit opioid use
      was obtained from monthly medical records. Binary logistic regression was used to
      investigate factors associated with illicit opioid use. RESULTS: Five hundred
      ninety-eight eligible MMT participants were used for data analysis. Variables
      such as age, gender, route of heroin use and daily MMT dosages were associated
      with illicit opioid use. Compared with MMT participants aged <40 years,
      participants aged 40-44 years (P = 0.027, OR = 0.57, 95 % CI 0.35-0.94), 45-49
      years (P < 0.001, OR = 0.41, 95 % CI 0.24-0.67) and >=50 years (P = 0.008, OR =
      0.52, 95 % CI 0.33-0.85) were more likely not to have illicit opioid use.
      Compared with male participants, females were more likely to have illicit opioid
      use (P = 0.044, OR = 1.53, 95 % CI 1.01-2.32). Compared with inhalation heroin
      abusers, abusers with route of inhalation + injection heroin use were more likely
      to have illicit opioid use (P = 0.009, OR = 2.00, 95 % CI 1.19-3.36). Compared
      with daily MMT dosages <60 mg participants, participants with daily MMT dosages
      >80 mg were more likely to have illicit opioid use (P = 0.003, OR = 2.37, 95 % CI
      1.35-4.15). CONCLUSIONS: Age, gender, route of heroin use and daily MMT dosages
      were associated with illicit opioid use. A tailored intervention is needed for a
      promotion of MMT.

PMID- 27699692
TI  - Psychological distress between chronic hemodialysis patients with and without low
      back pain.
AB  - OBJECTIVE: The aim of this study was to compare psychological distress between
      patients on chronic hemodialysis with and without chronic low back pain (CLBP).
      SUBJECTS AND METHODS: A total of 72 patients on chronic hemodialysis, aged 72.9
      +/- 10.8 years, were enrolled in this cross-sectional study. Psychological
      distress using the K6, questionnaire for CLBP, and physical activity using the
      tri-accelerometer were evaluated. RESULTS: Twenty-nine patients (40.3 %) were
      having CLBP. The K6 scores were 4.0 +/- 4.6 and physical activity (n = 55) was
      1.0 +/- 1.0 METs h/day. K6 scores in patients on chronic hemodialysis with CLBP
      were significantly higher than those in patients on chronic hemodialysis without
      CLBP even after adjusting for sex, age, duration of hemodialysis and physical
      activity. CONCLUSION: These results suggest that higher psychological distress
      was a fundamental feature in patients on chronic hemodialysis with CLBP.

PMID- 27699693
TI  - Elemental and immunohistochemical analysis of the lungs and hilar lymph node in a
      patient with asbestos exposure, a pilot study.
AB  - OBJECTIVES: Studies have shown that inhaled mine dust, such as asbestos, can be
      translocated to various organs including the lymph nodes. Recently, we have
      established a protocol that enables us to identify inhaled elements using
      paraffin embedded lung specimens by in-air microparticle-induced X-ray emission
      (micro-PIXE). However, little research has examined the concentration of these
      inhaled fibers in various organs or the mechanisms of their translocation. In
      this study, we compared the concentration of inhaled fibers in the lung
      parenchyma to the concentration in the hilar lymph node as well as to determine
      the elemental spatial distribution of the inhaled fibers in a patient with
      occupational asbestos exposure. METHODS: Lung tissues and hilar lymph node in a
      patient with asbestos exposure were used in this study. Elemental analysis was
      performed by in-air micro-PIXE. Immunohistochemical analysis was performed using
      anti CD163, smooth muscle actin, vimentin and beta-catenin antibody. RESULTS: The
      analysis revealed that the amount of inhaled silicon was approximately 6 times
      higher in the lymph node than in the lungs. The spatial analysis showed that
      silicon, iron and aluminium were co-localized in the hilar lymph node. The
      immunohistochemical analysis showed localized agreement of the inhaled fibers
      with macrophages, smooth muscle actin, and vimentin in the hilar lymph node.
      CONCLUSIONS: This study showed that in-air micro-PIXE could be useful for
      analyzing the elemental distribution and quantification of inhaled fibers in the
      human body. Furthermore, immunohistochemistry in combination with in-air micro
      PIXE analyses may help to determine the mechanism of mine dust distribution in
      vivo.

PMID- 27699694
TI  - Cognitive function is maintained in noninstitutionalized elderly Japanese
      requiring care with high levels of health-related quality of life.
AB  - BACKGROUND: Health-related quality of life (HRQOL) has been reported to be
      associated with cognitive function; however, whether or not this relationship
      involves causality is uncertain. This study aimed to determine whether HRQOL
      levels are associated with subsequent changes in cognitive function in elderly
      people requiring care. METHODS: Participants were 74 community-dwelling elderly
      people utilizing the long-term care service (69 % women) who underwent physical
      and psychological examinations at baseline and follow-up. The outcome was 2-year
      changes in Mini-Mental State Examination (?MMSE) score. The potential predictor
      was HRQOL level assessed by the EuroQol 5 dimension (EQ-5D) score (utility value)
      at baseline; other variables were body mass index (BMI), Barthel index, grip
      strength, Geriatric Depression Scale, serum albumin, and serum hemoglobin.
      Associations between EQ-5D and ?MMSE scores were assessed using correlation
      analysis, regression analysis, and analysis of covariance (ANCOVA). RESULTS: Mean
      age, BMI, and Barthel index at baseline were 81.6 years [standard deviation (SD)
      8.2], 21.1 kg/m2 (SD 4.0), and 79 (SD 20), respectively; the mean ?MMSE score was
      -2.2 (SD 5.1). EQ-5D was significantly correlated with ?MMSE (partial r = 0.375,
      P = 0.0012). The mean ?MMSE values of the 1st, 2nd, and 3rd EQ-5D quartiles were 
      4.2 (adjusted P = 0.0050), -2.6 (adjusted P = 0.0476), and -2.4 (adjusted P =
      0.0298), respectively, which were lower than the -0.1 of the reference 4th
      quartile. CONCLUSIONS: HRQOL as assessed by EQ-5D is associated with longitudinal
      cognitive decline in frail elderly people, and cognitive function may be
      maintained in individuals with high HRQOL levels.

PMID- 27699695
TI  - Associations of smoking status with other lifestyle behaviors are modified by sex
      and occupational category among urban civil servants in Japan.
AB  - OBJECTIVES: The aim of the present study was to examine the associations of
      current smoking with five other unhealthy lifestyle behaviors among urban civil
      servants in Japan according to sex and occupational category. METHODS: The study
      included 10,232 urban civil servants in Japan who presented for a health check-up
      in 2011. We analyzed data on anthropometric measurements and self-reported
      lifestyle factors. RESULTS: Current smokers had a higher BMI than never smokers
      in white-collar workers, but not in blue-collar workers of both sexes. There were
      strong associations of current smoking with irregular breakfasting regardless of
      sex and occupational category. In males, current smokers were less likely to take
      exercise than ex-smokers in both occupational categories. CONCLUSIONS: The
      associations of current smoking with other unhealthy behaviors were modified by
      sex and occupational category. These results are useful for understanding the
      health risks among smokers according to sex and occupational category.

PMID- 27699696
TI  - Neuromechanical Modulation of the Achilles Tendon During Bilateral Hopping in
      Patients with Unilateral Achilles Tendon Rupture, Over 1 Year After Surgical
      Repair.
AB  - BACKGROUND: Patients who have had an Achilles tendon (AT) rupture repaired are
      potentially at higher risk for re-rupture than those without previous rupture.
      Little attention has been given to the neuromechanical modulation of muscle
      tendon interaction and muscle activation profiles during human dynamic movements
      after AT rupture repair. OBJECTIVE: The purpose of this study was to examine
      muscle-tendon behavior and muscle activation during bilateral hopping. METHODS:
      We enrolled nine subjects who had undergone surgical repair of unilateral AT
      rupture within the past 1-2 years. Subjects performed bilateral hopping while we
      took ultrasound, kinematic, and electromyogram recordings and measurements. AT
      behaviors were also recorded. We then compared responses between values obtained
      from the ruptured AT leg (LEGATR) and non-ruptured AT leg (LEGNOR). RESULTS:
      During hopping, the AT stretching amplitudes were greater in the LEGATR than in
      the LEGNOR, although the peak AT force and stiffness were smaller in the LEGATR
      than in the LEGNOR. The AT negative mechanical work did not show any significant
      differences between both legs. However, positive works were significantly lower
      in the LEGATR than in the LEGNOR. Electromyogram patterns in both soleus and
      tibialis anterior muscles clearly differed after ground contact for the LEGATR
      and the LEGNOR. CONCLUSIONS: These results suggest that the repaired ruptured AT
      can be compliant and have insufficient Young's modulus, which can influence
      mechanical responses in muscle activities. The modulation of agonist-antagonist
      muscle activities corresponding to the different levels of stiffness between the
      LEGATR and the LEGNOR may not be fully functioning during the pre-activation
      phase.

PMID- 27699698
TI  - Sport and Transgender People: A Systematic Review of the Literature Relating to
      Sport Participation and Competitive Sport Policies.
AB  - BACKGROUND: Whether transgender people should be able to compete in sport in
      accordance with their gender identity is a widely contested question within the
      literature and among sport organisations, fellow competitors and spectators.
      Owing to concerns surrounding transgender people (especially transgender female
      individuals) having an athletic advantage, several sport organisations place
      restrictions on transgender competitors (e.g. must have undergone gender
      confirming surgery). In addition, some transgender people who engage in sport,
      both competitively and for leisure, report discrimination and victimisation.
      OBJECTIVE: To the authors' knowledge, there has been no systematic review of the
      literature pertaining to sport participation or competitive sport policies in
      transgender people. Therefore, this review aimed to address this gap in the
      literature. METHOD: Eight research articles and 31 sport policies were reviewed.
      RESULTS: In relation to sport-related physical activity, this review found the
      lack of inclusive and comfortable environments to be the primary barrier to
      participation for transgender people. This review also found transgender people
      had a mostly negative experience in competitive sports because of the
      restrictions the sport's policy placed on them. The majority of transgender
      competitive sport policies that were reviewed were not evidence based.
      CONCLUSION: Currently, there is no direct or consistent research suggesting
      transgender female individuals (or male individuals) have an athletic advantage
      at any stage of their transition (e.g. cross-sex hormones, gender-confirming
      surgery) and, therefore, competitive sport policies that place restrictions on
      transgender people need to be considered and potentially revised.

PMID- 27699697
TI  - Wrist Injuries in Tennis Players: A Narrative Review.
AB  - The wrist/hand complex forms the crucial final link in the kinetic chain between
      the body and the racquet and therefore has a number of important roles in the
      production of all tennis strokes. However, the internal and external loads that
      are created at the wrist during these strokes have the potential to contribute to
      pain and injury. Therefore, the purposes of this narrative review are to (1)
      determine the extent of the problem of wrist pain/injury in tennis players, (2)
      identify bony and soft tissue structures of the wrist that are susceptible to
      damage as a result of tennis play and (3) explore factors that may influence the
      development of wrist pain/injury in tennis players. The epidemiological data
      revealed two important points. First, some evidence suggests wrist pain/injury
      accounts for a higher percentage of total injuries in more recent studies (2014
      2015) than in early studies (1986-1995). Second, the relative frequency of wrist
      pain/injury compared with other well-recognized problem areas for tennis players
      such as the shoulder complex, elbow and lumbar spine is noticeably higher in more
      recent studies (2014-2015) than in early studies (1986-1995), particularly among
      females. Collectively, this would seem to indicate that the problem of wrist
      pain/injury has increased in the modern game. In fact, some wrist injuries appear
      to be related to the use of certain forehand grip types and the predominant use
      of the two-handed backhand. While the loads experienced at the wrist during
      tennis stroke production seem to be below threshold levels for a single event,
      the cumulative effects of these loads through repetition would appear to be an
      important consideration, especially when inadequate time is allowed to complete
      normal processes of repair and adaptation. This is supported by the evidence that
      most wrist injuries in tennis are associated with overuse and a chronic time
      course. The complex interaction between load, repetition, and training practices
      in tennis, particularly among young developing players who choose a path of early
      specialization, needs to be further explored.

PMID- 27699699
TI  - The Optimal Load for Maximal Power Production During Upper-Body Resistance
      Exercises: A Meta-Analysis.
AB  - BACKGROUND: External mechanical power is considered to be one of the most
      important characteristics with regard to sport performance. OBJECTIVE: The
      purpose of this meta-analysis was to examine the effect of load on kinetic
      variables such as mean and peak power during bench press and bench press throw,
      thus integrating the findings of various studies to provide the strength and
      conditioning professional with more reliable evidence upon which to base their
      program design. METHODS: A search of electronic databases (MEDLINE, PubMed,
      Google Scholar, and Web of Science) was conducted to identify all publications up
      to 31 October 2015. Hedges' g (95 % confidence interval) was estimated using a
      weighted random-effect model, due to the heterogeneity (I 2) of the studies.
      Egger's test was used to evaluate possible publication bias in the meta-analysis.
      A total of 11 studies with 434 subjects and 7680 effect sizes met the inclusion
      criterion and were included in the statistical analyses. Load in each study was
      labeled as one of three intensity zones: zone 1 represented an average intensity
      ranging from 0 to 30 % of one repetition maximum (1RM); zone 2 between 30 and 70
      % of 1RM; and zone 3 >= 70 % of 1RM. RESULTS: These results showed different
      optimal loads for each exercise examined. Moderate loads (from >30 to <70 % of
      1RM) appear to provide the optimal load for peak power and mean power in the
      bench press exercise. Lighter loads (<30 % of 1RM) appear to provide the highest
      mean and highest peak power production in the bench press throw exercise.
      However, a substantial heterogeneity was detected I 2 > 75 %. CONCLUSION: The
      current meta-analysis of published literature provides evidence for exercise
      specific optimal power loading for upper body exercises.

PMID- 27699702
TI  - Ethanol production from N-acetyl-D-glucosamine by Scheffersomyces stipitis
      strains.
AB  - N-acetyl-D-glucosamine (GlcNAc) is the building block of chitin, which is one of
      the most abundant renewable resources in nature after cellulose. Therefore, a
      microorganism that can utilize GlcNAc is necessary for chitin-based biorefinery.
      In this study, we report on the screening and characterization of yeast strains
      for bioethanol production from GlcNAc. We demonstrate that Scheffersomyces
      (Pichia) stipitis strains can use GlcNAc as the sole carbon source and produce
      ethanol. S. stipitis NBRC1687, 10007, and 10063 strains consumed most of the 50
      g/L GlcNAc provided, and produced 14.5 +/- 0.6, 15.0 +/- 0.3, and 16.4 +/- 0.3
      g/L of ethanol after anaerobic fermentation at 30  degrees C for 96 h. The
      ethanol yields of these strains were approximately 81, 75, and 82 % (mol
      ethanol/mol GlcNAc consumed), respectively. Moreover, S. stipitis NBRC10063
      maintained high GlcNAc-utilizing capacity at 35  degrees C, and produced 12.6 +/-
      0.7 g/L of ethanol after 96 h. This strain also achieved the highest ethanol
      titer (23.3 +/- 1.0 g/L) from 100 g/L GlcNAc. To our knowledge, this is the first
      report on ethanol production via fermentation of GlcNAc by naturally occurring
      yeast strains.

PMID- 27699700
TI  - Sitting Less and Moving More: Improved Glycaemic Control for Type 2 Diabetes
      Prevention and Management.
AB  - Epidemiological evidence indicates that excessive time spent in sedentary
      behaviours (too much sitting) is associated with an increased risk of type 2
      diabetes (T2D). Here, we highlight findings of experimental studies corroborating
      and extending the epidemiological evidence and showing the potential benefits for
      T2D of reducing and breaking up sitting time across the whole day. We also
      discuss future research opportunities and consider emerging implications for T2D
      prevention and management. This new evidence is stimulating an expansion of
      diabetes-related physical activity guidelines-suggesting that in addition to
      moderate-vigorous physical activity, reducing and regularly interrupting
      prolonged sitting time is likely to have important and varied benefits across the
      spectrum of diabetes risk.

PMID- 27699701
TI  - Oligosaccharides: a boon from nature's desk.
AB  - This article reviews the varied sources of oligosaccharides available in nature
      as silent health promoting, integral ingredients of plants as well as animal
      products like honey and milk. The article focuses on exotic and unfamiliar
      oligosaccharides like Galactooligosaccharides, Lactulose derived
      Galactooligosaccharides, Xylooligosaccharides, Arabinooligosaccharides and algae
      derived Marine oligosaccharides along with the most acknowledged prebiotic
      fructooligosaccharides. The oligosaccharides are named as on the grounds of the
      monomeric units forming oligomers with functional properties. The chemical
      structures, natural sources, microbial enzyme mediated synthesis and
      physiological effects are discussed. An elaborate account of the different types
      of oligosaccharides with special reference to fructooligosaccharides are
      presented. Finally, the profound health benefits of oligosaccharides are
      rigourously discussed limelighting its positive physiological sequel.

PMID- 27699703
TI  - Disruption of Pseudomonas putida by high pressure homogenization: a comparison of
      the predictive capacity of three process models for the efficient release of
      arginine deiminase.
AB  - Disruption of Pseudomonas putida KT2440 by high-pressure homogenization in a
      French press is discussed for the release of arginine deiminase (ADI). The enzyme
      release response of the disruption process was modelled for the experimental
      factors of biomass concentration in the broth being disrupted, the homogenization
      pressure and the number of passes of the cell slurry through the homogenizer. For
      the same data, the response surface method (RSM), the artificial neural network
      (ANN) and the support vector machine (SVM) models were compared for their ability
      to predict the performance parameters of the cell disruption. The ANN model
      proved to be best for predicting the ADI release. The fractional disruption of
      the cells was best modelled by the RSM. The fraction of the cells disrupted
      depended mainly on the operating pressure of the homogenizer. The concentration
      of the biomass in the slurry was the most influential factor in determining the
      total protein release. Nearly 27 U/mL of ADI was released within a single pass
      from slurry with a biomass concentration of 260 g/L at an operating pressure of
      510 bar. Using a biomass concentration of 100 g/L, the ADI release by French
      press was 2.7-fold greater than in a conventional high-speed bead mill. In the
      French press, the total protein release was 5.8-fold more than in the bead mill.
      The statistical analysis of the completely unseen data exhibited ANN and SVM
      modelling as proficient alternatives to RSM for the prediction and generalization
      of the cell disruption process in French press.

PMID- 27699704
TI  - Bio-degumming technology of jute bast by Pectobacterium sp. DCE-01.
AB  - Among industrial fiber crops, jute is ranked second to cotton in terms of yield
      and planting area worldwide. The traditional water retting and chemical semi
      degumming methods restrict the development of the jute industry. Jute fiber can
      be extracted from jute bast through mechanical rolling (preprocessing), culture
      of bacteria, soaking fermentation (liquor ratio = 10, inoculum size = 1 %,
      temperature = 35  degrees C, and time = 15 h), inactivation, washing, and drying.
      Pectobacterium sp. DCE-01 secretes key degumming enzymes: pectinase, mannase, and
      xylanase, which match well the main non-cellulosic components of jute bast.
      Compared with the traditional water retting degumming, the bio-degumming cycle is
      shortened from more than 10 days to 15 h. The proposed bio-degumming achieved
      higher efficiency and lower pollution than water retting and chemical semi
      degumming.

PMID- 27699705
TI  - Kinetics of nitrous oxide (N2O) formation and reduction by Paracoccus
      pantotrophus.
AB  - Nitrous oxide (N2O) is a powerful greenhouse gas emitted from wastewater
      treatment, as well as natural systems, as a result of biological nitrification
      and denitrification. While denitrifying bacteria can be a significant source of
      N2O, they can also reduce N2O to N2. More information on the kinetics of N2O
      formation and reduction by denitrifying bacteria is needed to predict and
      quantify their impact on N2O emissions. In this study, kinetic parameters were
      determined for Paracoccus pantotrophus, a common denitrifying bacterium.
      Parameters included the maximum specific reduction rates, [Formula: see text],
      growth rates, [Formula: see text], and yields, Y, for reduction of NO3- (nitrate)
      to nitrite (NO2-), NO2- to N2O, and N2O to N2, with acetate as the electron
      donor. The [Formula: see text] values were 2.9 gN gCOD-1 d-1 for NO3- to NO2-,
      1.4 gN gCOD-1 d-1 for NO2- to N2O, and 5.3 gN gCOD-1 d-1 for N2O to N2. The
      [Formula: see text] values were 2.7, 0.93, and 1.5 d-1, respectively. When N2O
      and NO3- were added concurrently, the apparent (extant) kinetics, [Formula: see
      text], assuming reduction to N2, were 6.3 gCOD gCOD-1 d-1, compared to 5.4 gCOD
      gCOD-1 d-1 for NO3- as the sole added acceptor. The [Formula: see text] was 1.6 d
      1, compared to 2.5 d-1 for NO3- alone. These results suggest that NO3- and N2O
      were reduced concurrently. Based on this research, denitrifying bacteria like P.
      pantotrophus may serve as a significant sink for N2O. With careful design and
      operation, treatment plants can use denitrifying bacteria to minimize N2O
      emissions.

PMID- 27699706
TI  - Effectiveness of a multidisciplinary risk assessment and management programme
      diabetes mellitus (RAMP-DM) on patient-reported outcomes.
AB  - Little is known about how the patient-reported outcomes is influenced by
      multidisciplinary-risk-assessment-and-management-programme for patients with
      diabetes mellitus (RAMP-DM). This paper aims to evaluate the effectiveness of
      RAMP-DM on patient-reported outcomes. This was a prospective longitudinal study
      on 1039 diabetes mellitus patients (714/325 RAMP-DM/non-RAMP-DM) managed in
      primary care setting. 536 and 402 RAMP-DM participants, and 237 and 187 non-RAMP
      DM participants were followed up at 12 and 24 months with completed survey,
      respectively. Patient-reported outcomes included health-related quality of life,
      change in global health condition and patient enablement measured by Short Form
      12 Health Survey version-2 (SF-12v2), Global Rating Scale, Patient Enablement
      Instrument respectively. The effects of RAMP-DM on patient-reported outcomes were
      evaluated by mixed effect models. Subgroup analysis was performed by stratifying
      haemoglobin A1c (HbA1c) (optimal HbA1c < 7 % and suboptimal HbA1c >= 7 %). RAMP
      DM with suboptimal HbA1c was associated with greater improvement in SF-12v2
      physical component summary score at 12-month (coefficient:3.80; P-value < 0.05)
      and 24-month (coefficient:3.82;P-value < 0.05), more likely to feel more enabled
      at 12-month (odds ratio: 2.57; P-value < 0.05), and have improved in GRS at 24
      month (odds ratio:4.05; P-value < 0.05) compared to non-RAMP-DM participants.
      However, there was no significant difference in patient-reported outcomes between
      RAMP-DM and non-RAMP-DM participants with optimal HbA1c. Participation in RAMP-DM
      is effective in improving physical component of HRQOL, Global Rating Scale and
      patient enablement among diabetes mellitus patients with suboptimal HbA1c, but
      not in those with optimal HbA1c. Patients with sub-optimal diabetes mellitus
      control should be the priority target population for RAMP-DM. This observational
      study design may have potential bias in the characteristics between groups, and
      randomized clinical trial is needed to confirm the results.

PMID- 27699710
TI  - Erratum to: Recent Progress in JAK Inhibitors for the Treatment of Rheumatoid
      Arthritis.

PMID- 27699707
TI  - Heterogeneity in glucose response curves during an oral glucose tolerance test
      and associated cardiometabolic risk.
AB  - We aimed to examine heterogeneity in glucose response curves during an oral
      glucose tolerance test with multiple measurements and to compare cardiometabolic
      risk profiles between identified glucose response curve groups. We analyzed data
      from 1,267 individuals without diabetes from five studies in Denmark, the
      Netherlands and the USA. Each study included between 5 and 11 measurements at
      different time points during a 2-h oral glucose tolerance test, resulting in
      9,602 plasma glucose measurements. Latent class trajectories with a cubic
      specification for time were fitted to identify different patterns of plasma
      glucose change during the oral glucose tolerance test. Cardiometabolic risk
      factor profiles were compared between the identified groups. Using latent class
      trajectory analysis, five glucose response curves were identified. Despite
      similar fasting and 2-h values, glucose peaks and peak times varied greatly
      between groups, ranging from 7-12 mmol/L, and 35-70 min. The group with the
      lowest and earliest plasma glucose peak had the lowest estimated cardiovascular
      risk, while the group with the most delayed plasma glucose peak and the highest 2
      h value had the highest estimated risk. One group, with normal fasting and 2-h
      values, exhibited an unusual profile, with the highest glucose peak and the
      highest proportion of smokers and men. The heterogeneity in glucose response
      curves and the distinct cardiometabolic risk profiles may reflect different
      underlying physiologies. Our results warrant more detailed studies to identify
      the source of the heterogeneity across the different phenotypes and whether these
      differences play a role in the development of type 2 diabetes and cardiovascular
      disease.

PMID- 27699708
TI  - Frequency of Cushing's syndrome due to ACTH-secreting adrenal medullary lesions:
      a retrospective study over 10 years from a single center.
AB  - Cushing's syndrome due to ectopic adrenocorticotropic hormone production from
      adrenal medullary lesions has occasionally been described. We retrospectively
      reviewed all 164 cases of Cushing's syndrome and 77 cases of pheochromocytomas
      during 10 years. Of all cases with Cushing's syndrome, only two cases (1.2 %)
      were due to ectopic adrenocorticotropic hormone production from adrenal medullary
      lesions (one case of pheochromocytoma and one case of adrenal medullary
      hyperplasia). Of all pheochromocytomas only the above-mentioned case (1.3 %) also
      gave rise to an ectopic adrenocorticotropic hormone syndrome. The clinical
      presentation of adrenocorticotropic hormone-secreting pheochromocytoma and
      adrenal medullary hyperplasia can be anything from mild to dramatic. These are
      rare conditions important to bear in mind in the workup of a patient with
      Cushing's syndrome or with pheochromocytoma. The identification of ectopic
      adrenocorticotropic hormone secretion from adrenal medullary lesions can be life
      saving.

PMID- 27699711
TI  - Erratum to: Measuring NLR Oligomerization II: Detection of ASC Speck Formation by
      Confocal Microscopy and Immunofluorescence.

PMID- 27699712
TI  - One Health: EcoHealth 2016: Welcome from the President of the International
      Association for Ecology and Health.

PMID- 27699713
TI  - Personal autonomy in health settings and Shi'i Islamic Jurisprudence: a
      literature review.
AB  - Respect for personal autonomy in decision-making is one of the four ethical
      principles in medical circumstances. This paper aims to present evidence that can
      be considered good exemplars in the clarification of the ethical viewpoints of
      the western and Shi'i Islamic perspectives on this issue. The method followed was
      originally a search in international indexing services in April 2016. Our
      findings point towards various controversies on individuals' autonomy lead to
      different decision making outcomes by health workers in both different
      traditions. We concluded that although Shi'i Islamic jurisprudence does not seem
      to allow for personal autonomy in the sense it is understood in a western
      context, evidence indicates that Shi'i Islamic jurisprudence respects personal
      autonomy.

PMID- 27699714
TI  - Investigating the Effect of Line Dipole Magnetic Field on Hydrothermal
      Characteristics of a Temperature-Sensitive Magnetic Nanofluid Using Two-Phase
      Simulation.
AB  - Hydrothermal characteristics of a temperature-sensitive magnetic nanofluid
      between two parallel plates are investigated in the presence of magnetic field
      produced by one or multiple line dipole(s) using the two-phase mixture model. As
      the nanofluid reaches the region where the magnetic field is applied, a rotation
      is developed due to the dependency of magnetization on temperature. This can lead
      to mixing in the flow and more uniform distribution of temperature due to the
      disturbance caused in the boundary layer, and consequently, enhancement in
      convective heat transfer. The results indicate that the disturbance in boundary
      layer adjacent to the lower wall is more significant than the upper wall. By
      application of the magnetic field, the convective heat transfer increases locally
      for both walls. Due to the intensified mixing, a sudden pressure drop occurs when
      the fluid reaches the region where the magnetic field is applied. For greater
      magnetic field strengths and lower Reynolds numbers, the improvement in
      convective heat transfer is more significant. For small magnetic field strengths,
      the effect of applying magnetic field on the upper wall is much smaller than that
      on the lower wall; however, this effect becomes almost the same for both walls at
      great magnetic field strengths.

PMID- 27699715
TI  - L-Cysteine-Assisted Synthesis of Urchin-Like gamma-MnS and Its Lithium Storage
      Properties.
AB  - MnS has been attracting more and more attentions in the fields of lithium ion
      batteries (LIBs) because of its high energy density and low voltage potential. In
      this paper, we present a simple method for the preparation of urchin-like gamma
      MnS microstructures using L-cysteine and MnCl2 . 4H2O as the starting materials.
      The urchin-like gamma-MnS microstructures exhibit excellent cycling stability
      (823.4 mA h g-1 at a current density of 500 mA g-1, after 1000 cycles). And the
      discharge voltage is about 0.75 V, making it a good candidate for the application
      as the anode material in LIBs. SEM, TEM, and XRD were employed to inspect the
      changes of the active materials during the electrochemical process, which clearly
      indicate that the structural pulverization and reformation of the gamma-MnS
      microstructures play important roles for the maintenance of the electrochemical
      performance during the charge/discharge process.

PMID- 27699716
TI  - Comparison of Silicon Nanocrystals Prepared by Two Fundamentally Different
      Methods.
AB  - This work compares structural and optical properties of silicon nanocrystals
      prepared by two fundamentally different methods, namely, electrochemical etching
      of Si wafers and low-pressure plasma synthesis, completed with a mechano-photo
      chemical treatment. This treatment leads to surface passivation of the
      nanoparticles by methyl groups. Plasma synthesis unlike electrochemical etching
      allows selecting of the particle sizes. Measured sizes of the nanoparticles by
      dynamic light scattering show 3 and 20 nm for electrochemically etched and plasma
      synthetized samples, respectively. Plasma-synthetized 20-nm particles do not
      exhibit photoluminescence due to absence of quantum confinement effect, and
      freshly appeared photoluminescence after surface passivation could indicate
      presence of organic molecules on the nanoparticle surface, luminescing instead of
      nanocrystal core. Electrochemically etched sample exhibits dramatic changes in
      photoluminescence during the mechano-photo-chemical treatment while no
      photoluminescence is observed for the plasma-synthetized one. We also used the
      Fourier transform infrared spectroscopy for comparison of the chemical changes
      happened during the treatment.

PMID- 27699717
TI  - MPTP Induces Systemic Parkinsonism in Middle-Aged Cynomolgus Monkeys: Clinical
      Evolution and Outcomes.
AB  - In this study, we developed a systemic PD model in middle-aged cynomolgus monkeys
      using individualized low-dose MPTP, to explore effective indicators for the early
      prediction of clinical outcomes. MPTP was not stopped until the animals showed
      typical PD motor symptoms on days 10 to 13 after MPTP administration when the
      Kurlan score reached 10; this abrogated the differences in individual
      susceptibility to MPTP. The clinical symptoms persisted, peaking on days 3 to 12
      after MPTP withdrawal (rapid progress stage), and then the Kurlan score
      plateaued. A Kurlan score at the end of the rapid progress stage >15 reflected
      stable or slowly-progressive PD, while a score <15 indicated spontaneous
      recovery. The entire clinical evolution and outcome of the systemic PD model was
      characterized in this study, thus providing options for therapeutic and
      translational research.

PMID- 27699718
TI  - Olfactory Dysfunction in Parkinson's Disease Patients with the LRRK2 G2385R
      Variant.
AB  - Olfactory dysfunction has been reported in Parkinson's disease (PD) patients
      carrying the LRRK2 G2019S variant in Caucasians but rarely in those with the
      LRRK2 G2385R variant. In this study, we performed genotyping for the LRRK2 G2385R
      variant in PD patients recruited from the Movement Disorder Clinic of Xuanwu
      Hospital in Beijing and in healthy controls randomly selected from the Beijing
      Longitudinal Study on Aging cohort. The "five-odor olfactory detection array", an
      olfactory threshold test, was used to assess olfactory function. One hundred and
      eighty-six participants were enrolled, comprising 43 PD patients without (iPD)
      and 25 with (LRRK2-PD) the LRRK2 G2385R variant, and 118 healthy controls. Our
      results showed that the threshold of olfactory identification was significantly
      worse in PD patients than in controls, but not significantly different between
      the iPD and LRRK2-PD groups. These findings suggested that although olfactory
      function in LRRK2-PD patients is impaired, it is similar to that in iPD patients.

PMID- 27699719
TI  - 177Lu-PSMA-617 radioligand therapy of mCRPC: evaluation criteria of response.

PMID- 27699720
TI  - Preclinical in vivo and in vitro comparison of the translocator protein PET
      ligands [18F]PBR102 and [18F]PBR111.
AB  - PURPOSE: To determine the metabolic profiles of the translocator protein ligands
      PBR102 and PBR111 in rat and human microsomes and compare their in vivo binding
      and metabolite uptake in the brain of non-human primates (Papio hamadryas) using
      PET-CT. METHODS: In vitro metabolic profiles of PBR102 and PBR111 in rat and
      human liver microsomes were assessed by liquid chromatography-tandem mass
      spectrometry. [18F]PBR102 and [18F]PBR111 were prepared by nucleophilic
      substitution of their corresponding p-toluenesulfonyl precursors with
      [18F]fluoride. List mode PET-CT brain imaging with arterial blood sampling was
      performed in non-human primates. Blood plasma measurements and metabolite
      analysis, using solid-phase extraction, provided the metabolite profile and
      metabolite-corrected input functions for kinetic model fitting. Blocking and
      displacement PET-CT scans, using PK11195, were performed. RESULTS: Microsomal
      analyses identified the O-de-alkylated, hydroxylated and N-de-ethyl derivatives
      of PBR102 and PBR111 as the main metabolites. The O-de-alkylated compounds were
      the major metabolites in both species; human liver microsomes were less active
      than those from rat. Metabolic profiles in vivo in non-human primates and
      previously published rat experiments were consistent with the microsomal results.
      PET-CT studies showed that K1 was similar for baseline and blocking studies for
      both radiotracers; VT was reduced during the blocking study, suggesting low non
      specific binding and lack of appreciable metabolite uptake in the brain.
      CONCLUSIONS: [18F]PBR102 and [18F]PBR111 have distinct metabolic profiles in rat
      and non-human primates. Radiometabolites contributed to non-specific binding and
      confounded in vivo brain analysis of [18F]PBR102 in rodents; the impact in
      primates was less pronounced. Both [18F]PBR102 and [18F]PBR111 are suitable for
      PET imaging of TSPO in vivo. In vitro metabolite studies can be used to predict
      in vivo radioligand metabolism and can assist in the design and development of
      better radioligands.

PMID- 27699723
TI  - Erratum to: Early Postpartum Glucose Testing in Women with Gestational Diabetes
      Mellitus.

PMID- 27699721
TI  - Efficacy of long-term tenofovir-based rescue therapy in patients with chronic
      hepatitis B refractory to nucleoside/nucleotide analogs.
AB  - BACKGROUND: Few studies have investigated the efficacy of long-term tenofovir
      disoproxil fumarate (TDF)-based rescue therapy in patients with chronic hepatitis
      B refractory to nucleoside/nucleotide analogs. METHODS: We retrospectively
      analyzed 40 Japanese patients with chronic hepatitis B refractory to
      nucleoside/nucleotide analogs who received TDF-based rescue therapy [TDF
      monotherapy, TDF plus lamivudine (LAM) combination therapy, or TDF plus entecavir
      (ETV) combination therapy] followed up for a median of 45 months (range 14-99
      months). Viral response, changes in hepatitis B surface antigen levels from the
      baseline, and viral breakthrough during therapy were analyzed. RESULTS: The
      proportion of patients with undetectable serum hepatitis B virus (HBV) DNA levels
      (less than 2.1 log copies per milliliter) (viral response) during TDF-based
      rescue therapy was 68, 78, 85, 88, 83, 81, 88, and 100 % at 0.5, 1, 1.5, 2, 2.5,
      3, 3.5, and 4 years respectively. There were no differences in the viral response
      rate between the TDF plus LAM group and the TDF plus ETV group. The mean
      reduction from the baseline in hepatitis B surface antigen levels in patients
      with LAM-resistant HBV was greater than the reductions in patients with adefovir
      dipivoxil (ADV)-resistant or ETV-resistant HBV at 2 and 3 years (P = 0.024, and P
      = 0.025 respectively). However, two patients with ADV- or ETV-resistant HBV at
      the baseline developed viral breakthrough during TDF-based rescue therapy.
      CONCLUSIONS: Long-term therapy with a TDF-based rescue regimen demonstrated high
      viral suppression in patients in whom LAM plus ADV combination therapy, ETV plus
      ADV combination therapy, or ETV monotherapy had failed. However, patients with
      ADV- or ETV-resistant HBV at the baseline may develop viral breakthrough and
      resistance, and careful follow-up is advised.

PMID- 27699725
TI  - Arthroscopic Lateral Retinacular Release and Modified Elmslie-Trillat Operation
      Improve Severe Isolated Lateral Patello-Femoral Osteoarthritis.
AB  - To evaluate whether arthroscopic lateral retinacular release and the modified
      Elmslie-Trillat operation improve osteoarthritis (OA) progression and clinical
      outcomes in patients with severe isolated lateral patello-femoral OA. Nine women
      (11 knees) and one man (one knee) with isolated late-stage lateral patello
      femoral OA underwent surgery. The severity of patello-femoral OA was recorded
      using the Merchant method, while the level of pain and anterior knee function
      were scored using the visual analogue scale (VAS) and Kujala knee scores,
      respectively. The articular cartilage was graded under arthroscopy using the
      Outerbridge classification. All of the patients underwent the modified Elmslie
      Trillat operation after arthroscopic surgery, including lateral retinacular
      release. Ten patients (12 knees) had a mean 6.45 +/- 0.80 mm of medial transfer,
      6.02 +/- 0.80 mm of anterior transfer of the tibial tubercle, and follow-up of
      67.0 months. The mean VAS and Kujala knee scores improved from 8 +/- 0.17
      preoperatively to 2.33 +/- 0.33 on the last follow-up and from 43.08 +/- 2.09 to
      68.83 +/- 2.59, respectively (both p < 0.001). Postoperatively, all had improved
      subchondral bone remodeling, including cyst resolution, density and trabeculae
      normalization, and subchondral smoothing in the patello-femoral compartment. The
      patello-femoral joint space and patellar thickness increased from 0.39 +/- 0.16
      mm to 1.77 +/- 0.18 mm and from 18.28 +/- 0.67 mm to 19.60 +/- 0.69 mm,
      respectively (p < 0.001 and p = 0.005). Treatment of severe isolated lateral
      patello-femoral OA using arthroscopic lateral retinacular release and the
      modified Elmslie-Trillat operation can improve pain relief, functional outcomes,
      and subchondral bone remodeling, and also restore the patello-femoral joint space
      and patellar thickness. Prompt transfer of the tibial tubercle seems to reverse
      the progress of OA radiographically.

PMID- 27699724
TI  - Comparing epsilon-Aminocaproic Acid and Tranexamic Acid in Reducing Postoperative
      Transfusions in Total Knee Arthroplasty.
AB  - Multiple studies have shown tranexamic acid (TXA) to reduce blood loss and
      transfusion rates in patients undergoing total knee arthroplasty (TKA).
      Accordingly, TXA has become a routine blood conservation agent for TKA. In
      contrast, epsilon-aminocaproic acid (EACA), a similar acting antifibrinolytic to
      TXA, has been less frequently used. This study evaluated whether EACA is as
      efficacious as TXA in reducing postoperative blood transfusion rates and compared
      the cost per surgery between agents. A multicenter retrospective chart review of
      elective unilateral TKA from April 2012 through December 2014 was performed. Five
      hospitals within a health care system participated. Data collected included age,
      gender, severity of illness score, use of antifibrinolytic and dose, red blood
      cell (RBC) transfusions and the number of units, and preadmission and discharge
      hemoglobin (Hb). Dosing of the antifibrinolytic differed based on the agent used,
      5 or 10 g (based on weight) for EACA versus 1 g for TXA. The institutional
      acquisition cost of each antifibrinolytic was obtained and averaged over the
      study period. Of 2,922 primary unilateral TKA cases, 820 patients received EACA,
      610 patients received TXA, and 1,492 patients received no antifibrinolytic
      (control group). Compared with the control group both EACA and TXA groups had
      significantly fewer patients transfused (EACA 2.8% [p < 0.0001], TXA 3.2% [p <
      0.0001] vs. control 10.8%) and lower mean RBC units transfused per patient (EACA
      0.05 units/patient [pt] [p < 0.0001], TXA 0.05 units/pt [p < 0.0001] vs. control
      0.19 units/pt]. There was no difference in mean RBC units transfused per patient,
      percentage of patients transfused, and discharge Hb levels between the EACA and
      TXA groups (p = 0.822, 0.236, and 0.322, respectively). Medication acquisition
      cost for EACA averaged $2.23 per surgery compared with TXA at $39.58 per surgery.
      Administration of EACA or TXA significantly decreased postoperative transfusion
      rates compared with no antifibrinolytic therapy. Utilization of EACA for
      unilateral TKA proved to be comparable to TXA in all studied aspects at a lower
      cost. The level of evidence for the study is Level 3.

PMID- 27699722
TI  - Imaging as an Outcome Measure in Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous
      system. Magnetic resonance imaging (MRI) is sensitive to lesion formation both in
      the brain and spinal cord. Imaging plays a prominent role in the diagnosis and
      monitoring of MS. Over a dozen anti-inflammatory therapies are approved for MS
      and the development of many of these medications was made possible through the
      use of contrast-enhancing lesions on MRI as a phase II outcome. A similar phase
      II outcome method for the neurodegeneration that underlies progressive courses of
      the disease is still unavailable. Although magnetic resonance is an invaluable
      tool for the diagnosis and monitoring of treatment effects in MS, several imaging
      barriers still exist. In general, MRI is less sensitive to gray matter lesions,
      lacks pathological specificity, and does not provide quantitative data easily.
      Several advanced imaging methods including diffusion tensor imaging,
      magnetization transfer, functional MRI, myelin water fraction imaging, ultra-high
      field MRI, positron emission tomography, and optical coherence tomography of the
      retina study promising ways of overcoming the difficulties in MS imaging.

PMID- 27699726
TI  - Modified Elmslie-Trillat Procedure for Recurrent Dislocation of the Patella.
AB  - Many groups have reported good to excellent clinical outcomes of the Elmslie
      Trillat (ET) procedure for recurrent dislocation of the patella. However, the
      mean follow-up period of these studies was no more than 5 years. We hypothesized
      that the long-term postoperative outcomes of the modified ET procedure for
      recurrent dislocation of the patella would be acceptable compared with those of
      other procedures. The long-term postoperative outcomes of patients treated with
      the modified ET procedure were examined. A total of 31 knees in 27 patients with
      recurrent dislocation of the patella who underwent a modified ET procedure
      (without medial capsular plication) were evaluated. The mean follow-up period was
      13.0 years. Pre- and postoperative radiographs were examined to determine the Q
      angle, tilting angle, lateral shift ratio, sulcus angle, congruence angle, and
      Insall-Salvati index. Clinical outcomes were evaluated based on the Fulkerson
      patellofemoral joint evaluation score, Kujala score, and the presence of the
      apprehension sign. Radiological evaluation revealed significant postoperative
      improvements in the Q-angle, tilting angle, lateral shift ratio, congruence
      angle, Kujala score, and Fulkerson score (p < 0.001). Sixty-eight percent of all
      patients had a "good" or "excellent" Fulkerson score. The apprehension sign
      continued to be shown for six knees. Progression of osteoarthritic changes was
      observed in three knees, and one knee was symptomatic. The modified ET procedure
      provided satisfactory outcomes based on radiological and clinical evaluations.
      These results show the long-term effectiveness and safety of the modified ET
      procedure for recurrent patellar dislocation.

PMID- 27699728
TI  - Multicenter, Multisurgeon Research Groups Updates.

PMID- 27699727
TI  - A Comparison of Large Soft Palate Defect Reconstruction Using the New "Tunnel
      Structure" and Traditional "Port Structure" Methods.
AB  - Background For soft palate defects of more than two-thirds, we previously
      described the bent anterolateral thigh (ALT) method in which the pharyngeal
      isthmus was reconstructed as a tunnel structure. In this study, we compared the
      new "tunnel structure" reconstruction in our bent ALT flap method and the
      traditional "port structure" reconstruction. Methods From April 2010 to March
      2015, 25 patients in Saitama Cancer Center (Saitama, Japan) underwent
      oropharyngeal tumor resection including soft palate resection. In patients who
      had soft palate resection of less than two-thirds, the Gehanno method was
      performed in 10 patients (the data were shown as a comparison). In patients who
      had soft palate resection of more than two-thirds, the pharyngeal isthmus was
      reconstructed as a tunnel structure using the bent ALT flap method in eight
      patients and as a port structure in seven patients. The functional outcomes were
      assessed by interviewing patients about their symptoms and measuring the standard
      articulation test. Results Postoperative function was favorably maintained at
      equal levels in the tunnel structure reconstruction group and the Gehanno method
      group at approximately 12 months postoperation. However, in most patients in the
      port structure reconstruction group, the pharyngeal isthmus became larger after
      12 months postoperation and the articulation test was significantly worse than
      the Gehanno group and the tunnel group. Conclusion The bent ALT flap method had
      superior results to the conventional method. Thus the pharyngeal isthmus should
      be reconstructed as a tunnel structure for patients with soft palate defects of
      more than two-thirds.

PMID- 27699730
TI  - Management of Coagulopathy in Postpartum Hemorrhage.
AB  - The purpose of this article is to review the use of blood products and hemostatic
      agents in the management of coagulopathy at the time of postpartum hemorrhage.
      Blood product administration strategies are broadly reviewed, including the role
      of the blood bank, the role of massive transfusion protocols, the role of
      laboratory monitoring, and the role of anesthesia management. Aspects of patient
      blood management are discussed. The concept refers to an evidence-based,
      comprehensive, multidisciplinary approach to optimizing the care of patients who
      might need transfusion and includes measures to avoid or minimize transfusion
      such as preoperative anemia management, cell salvage, and the use of hemostatic
      medication to reduce bleeding. The contributions of individual blood components
      red blood cells, plasma, cryoprecipitate, and platelets-are described. Current
      data regarding the complementary role of hemostatic agents-antifibrinolytic
      agents and clotting factor concentrates-are presented. Two developments in blood
      component pathogen reduction are introduced.

PMID- 27699729
TI  - The Management of Factor XI Deficiency in Pregnancy.
AB  - Management of factor XI (FXI) deficiency in pregnancy is complicated by lack of
      correlation between FXI level and bleeding risk. Clinicians should be vigilant
      about the potential for prolonged or excessive bleeding following miscarriage or
      termination of pregnancy, or postpartum hemorrhage (PPH). A multidisciplinary
      approach along with an individual care plan is recommended to prevent bleeding
      complications. Assessment of bleeding history, FXI level, and global tests of
      hemostasis can aid management decisions regarding hemostatic prophylaxis. The
      risk of PPH can be minimized by obstetric measures to avoid uterine atony and
      genital trauma, in addition to provision of appropriate hemostatic prophylaxis
      for labor and delivery. Women with FXI deficiency can be given the option of
      regional anesthesia, provided that prior consideration has been given to
      assessment of potential bleeding risk and appropriate treatment strategies are
      implemented. Antifibrinolytic agents are effective for the majority of women with
      FXI deficiency, but those with severe deficiency/phenotype require FXI
      concentrate. Recombinant activated factor VII (rFVIIa) has also been used
      successfully to prevent bleeding in FXI deficiency. However, all treatments
      should be used with caution in pregnancy due to thrombogenic potential. Neonatal
      bleeding complications are rare in FXI deficiency; however, hemostatic assessment
      and cover are important for invasive procedures such as circumcision.

PMID- 27699731
TI  - The Effect of Intramural Botulinum Toxin Injections on the Elongation of the
      Piglet Oesophagus Is Time Dependent.
AB  - Introduction One in 4,000 infants is born with oesophageal atresia. Approximately
      15% of these have a long gap oesophageal atresia, where primary anastomosis is
      difficult or impossible. Previous studies have shown an effect of intramural
      botulinum toxin type A (BTX-A) injections on the elongation and max load of the
      esophagus 1 hour after injection. We hypothesized that a longer waiting period of
      2 hours could increase this effect. Methods Forty-five piglets were randomized
      into three groups. Two treatment groups received 2 units/kg of BTX-A and one
      group received saline. After 1 or 2 hours, a segment of the esophagus was
      harvested and put in a stretch-tension device to assess elongation and max load.
      Results Elongation from preload to max load and percentage elongation in the BTX
      A 2h group (17.09 mm, 46.46%) was significantly higher compared with the BTX-A 1h
      group (13.59 mm, 40.16%) and the placebo group (13.77 mm, 39.92%). Conclusion
      Elongation of the piglet esophagus was significantly improved with a 2-hour
      waiting period after BTX-A injection. Injections with BTX-A could be useful in
      oesophageal atresia, where primary anastomosis is not possible.

PMID- 27699732
TI  - A New Era in Diagnostic Ultrasound, Superb Microvascular Imaging: Preliminary
      Results in Pediatric Hepato-Gastrointestinal Disorders.
AB  - Introduction Superb microvascular imaging is a new ultrasound image processing
      technique that uses advanced clutter suppression to extract flow signals from
      vessels and which helps us visualize very small vascular structures that were not
      previously visible without the use of a contrast agent. We herein analyzed the
      usefulness of superb microvascular imaging in the diagnosis of hepato
      gastrointestinal disorders in pediatric patients. Materials and Methods Fifty-six
      pediatric patients who underwent a total of 81 superb microvascular imaging
      examinations with an Aplio 300 ultrasound system (Toshiba Medical Systems, Tokyo,
      Japan) were enrolled in this study. The subjects underwent conventional
      ultrasound examinations, including Doppler imaging followed by superb
      microvascular imaging. The superb microvascular imaging findings and standard
      imaging were compared. All of the examinations were performed without sedation.
      Results The average age of the patients (male, n = 38; female, n = 18) was 4
      years. The clinical diagnoses included hepatobiliary disorders (n = 29), acute
      appendicitis (n = 10), and other intestinal disorders (n = 17). The target organs
      for superb microvascular imaging were the liver, appendix, rectum, intestine,
      gallbladder, and lymph node. In most of the patients, superb microvascular
      imaging achieved the excellent visualization of microvascular structures,
      revealing abnormal vasculature in 21 out of 46 (45.7%) examinations of the liver,
      9/9 (100%) examinations of the appendix, 0/11 (0%) examinations of the rectum,
      9/11 (81.8%) examinations of the intestine, 0/1 (0%) examinations of the
      gallbladder, and 3/3 (100%) examinations of the lymph nodes. Superb microvascular
      imaging was superior to Doppler imaging for depicting the microvascular
      structures. Conclusions Superb microvascular imaging is especially useful for
      depicting the microvascular flow and can aid in the diagnosis and treatment
      planning for pediatric patients with hepato-gastrointestinal disorders.

PMID- 27699733
TI  - Surgical Treatment of Childhood Inflammatory Myofibroblastic Tumors.
AB  - Aim A retrospective study was performed to evaluate the clinical features,
      diagnostic methods, and treatment alternatives of childhood inflammatory
      myofibroblastic tumors (IMTs). Patients and Methods Patients who underwent
      surgical treatment for IMT between 2000 and 2015 were evaluated for age, sex,
      presenting symptoms, physical examination findings, diagnostic methods, treatment
      modalities, histopathologic findings, and results of surgical treatment during
      long-term follow-up. Results Eleven patients who underwent surgical treatment
      were included in the study. Male:female ratio was 7:4 and the mean age of the
      patients was 6.09 years (1-10 years). Presenting symptoms were respiratory
      difficulty, cough (n = 7, 63.3%), abdominal pain, vomiting (n = 2, 18.8%), loss
      of body weight (n = 1, 9.09%), palpable mass (n = 1, 9.09%), and rectal bleeding
      (n = 1, 9.09%). Ultrasonography (n = 4, 36.3%) and computed tomography (n = 9,
      81.1%) were used for diagnosis. Localizations of tumors were lungs (n = 5,
      45.4%), mediastinum (n = 2, 18.1%), spleen (n = 1, 9.09%), neck (n = 1, 9.09%),
      colon (n = 1, 9.09%), and rectum (n = 1, 9.09%). The mean size of mass was 6.6 cm
      (2-12 cm) and six patients were diagnosed with preoperative biopsy. Lung
      lobectomy (right lower lobe; n = 3, right middle and lower lobe; n = 2), total
      resection of mass with adjacent bowel (n = 2), partial splenectomy (n = 1), total
      resection of neck mass (n = 1), and incomplete resection (n = 2) were the choice
      of surgical treatment. Incomplete resection was performed in masses closely
      adjacent to atrium and mediastinal structures. In histopathologic evaluation,
      surgical margins were free of tumor in four cases, positive in six cases, and
      were not reported in one case. Anaplastic lymphoma kinase (ALK) positivity was
      detected in six cases, negative in two cases, and was not evaluated in three
      cases. Two cases who had residual mass with positive ALK received chemotherapy.
      Mean follow-up time was 68.2 months (5 months to 12 years). During follow-up,
      there was no recurrence or distant metastasis. Ten patients survived and one
      patient was lost to follow-up. Conclusion IMT is a rare tumor of childhood with a
      spectrum of clinical findings because of variable localization. Surgical
      treatment is the first choice of treatment. Patients with residual mass and ALK
      positivity may require medical treatment. In our series, long-term survival of
      patients was favorable in patients with total resection.

PMID- 27699734
TI  - [Overview of Endometrial Cancer].
AB  - Endometrial cancer is the most common gynecological cancer and the sixth most
      common cancer among women in Taiwan. Risk factors for endometrial cancer include
      obesity, long-term estrogen replacement therapy, diabetes mellitus, hypertension,
      nulliparty, early age at menarche, late age at menopause, and tamoxifen therapy.
      Most women with endometrial cancer exhibit abnormal uterine bleeding. Endometrial
      cancer is often diagnosed at stage I. Surgery alone is the primary treatment for
      stage I endometrial cancer. Fortunately, mortality rates for endometrial cancer
      are relatively low, with a 5-year survival rate of 81% among women who are
      diagnosed with endometrial cancer in Taiwan. However, the common side effects of
      treatment, including infertility, surgical menopause, lymphedema of the lower
      extremities, sexual dysfunction, distress, and fatigue, impact significantly on
      the quality of life of patients. Lifestyle changes such as keeping physically
      active and eating a diet that is high in fruit and vegetables may alleviate
      symptoms and improve quality of life in women who have undergone treatment for
      endometrial cancer.

PMID- 27699735
TI  - [Treatment Decision-Making Process of Cancer Patients].
AB  - The decision-making process that is used by cancer patients to determine their
      treatment has become more multi-foci, difficult and complicated in recent years.
      This has in part been attributed to the increasing incidence rate of cancer in
      Taiwan and the rapid development of medical technologies and treatment
      modalities. Oncology nurses must assist patients and family to make informed and
      value-based treatment decisions. Decision-making is an information process that
      involves appraising one's own expectation and values based on his/her knowledge
      on cancer and treatment options. Because cancer treatment involves risks and
      uncertainties, and impacts quality of life, the treatment decision-making for
      cancer is often stressful, or even conflicting. This paper discusses the decision
      making behaviors of cancer patients and the decisional conflict, participation,
      and informational needs that are involved in cancer treatment. The trend toward
      shared decision-making and decisional support will be also explored in order to
      facilitate the future development of appropriate clinical interventions and
      research.

PMID- 27699736
TI  - [Chemotherapy-Induced Amenorrhea and Menopause Symptoms in Women With Breast
      Cancer].
AB  - Chemotherapy is a common adjuvant therapy for breast cancer that improves
      survival rates by killing residual cancer cells. However, this intervention may
      damage the germ cells within the ovary and interrupt the menstrual cycle,
      ultimately leading to chemotherapy-induced amenorrhea (CIA). The incidence of CIA
      depends on how broadly this term is defined. Around 75% of premenopausal breast
      cancer women treated with chemotherapy will develop CIA. Age, having a relatively
      long chemotherapy cycle duration, being estrogen-receptor positive, and using
      Tamoxifen all increase the risk of CIA. Although CIA may be associated with
      better prognosis outcomes, breast cancer women must subsequently deal with the
      various menopausal symptoms that are associated with a CIA-induced drop in
      estrogen level (such as cognitive function decline, physical and psychological
      symptoms, vasomotor symptoms, reproductive and sexual function problems, and body
      weight change). The present article describes the female menstrual cycle, the
      mechanism and risk factors of CIA, and the range of menopausal symptoms.
      Furthermore, we summarized methods of assessing menopausal symptoms and compared
      five common rating scales of menopausal symptoms. By better understanding the
      potential menopausal symptoms, researchers and clinicians may then select the
      most appropriate scale based on the situational needs in order to evaluate the
      severity of menopausal symptoms that are experienced by breast cancer women.

PMID- 27699737
TI  - [Cancer-Related Posttraumatic Stress Symptoms in Patients With Cancer].
AB  - At least half of patients with cancer experience emotional distress (e.g.,
      posttraumatic stress symptoms). Most of the studies on the emotional distress of
      Taiwanese cancer patients have focused on issues of depression rather than on
      posttraumatic stress disorder. The scope of the present article covers the
      definitions of cancer-related posttraumatic stress disorder (CR-PTSD) and cancer
      related posttraumatic stress symptoms (CR-PTSS), identifies the differences and
      similarities between professional interview and self-administered measurement
      tools and their applications; analyzes the prevalence of CR-PTSD and CR-PTSS;
      identifies the possible contributing sociodemographic (younger age, female, low
      education, low socio-economic status), clinical (advanced stage, undergoing
      chemotherapy, just completed the therapy), and psychosocial (negative
      psychological traits, poor social support, and insufficient coping strategies) of
      CR-PTSD and CR-PTSS; and aggregates the effects of cognitive and psychosocial
      interventions on CR-PTSD and CR-PTSS. Furthermore, recommendations for clinical
      practice and research are discussed. This article is expected to provide
      practicing nurses with a basic concept of caring for emotional distress and to
      inspire researchers to conduct further study of issues related to CR-PTSD and CR
      PTSS.

PMID- 27699738
TI  - [The Mediating Role of Parenting Self-Efficacy on Parenting Stress and Quality of
      Life in Parents of Young Children With Developmental Delay].
AB  - BACKGROUND: Previous studies indicate that parents of developmentally delayed
      children have higher parenting stress (PS) and lower quality of life (QoL) than
      parents of healthy children. Parenting self-efficacy (PSE) may mediate the
      effects of PS on the QoL of parents. PURPOSE: The present study explores the
      mediating role of PSE between PS and the QoL of parents of developmentally
      delayed children and compares the differences in several variables between
      fathers and mothers. METHODS: A cross-sectional research design was used to study
      a sample of 70 parent dyads. Instruments used were the Basic Information Form,
      Parenting Stress Index Short Form (PSI-SF), Parenting Self-efficacy Scale (PSE
      Scale), and World Health Organization Quality of Life-BREF Taiwan version (WHOQOL
      BREF). RESULTS: (1) Participants had a moderate level of QoL, PS, and PSE. (2)
      The PS of participants was significantly and negatively correlated with both QoL
      and PSE while their PSE was significantly and positively correlated with QoL. (3)
      The PSE of the fathers completely mediated the effects of PS on their QoL (p <
      .001), accounting for 62.2% of observed variation, while the PSE of the mothers
      partially mediated the effects of PS on their QoL (p < .05), accounting for 59.5%
      of observed variation. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: PSE was
      identified as the mediator between PS and QoL in both fathers and mothers. The
      PSE of the fathers completely mediated the effect of PS on QoL, while the PSE of
      the mothers partially mediated the effect of PS on QoL. Further research that
      explores the factors that affect the QoL of parents and then uses the results to
      develop interventions to enhance the PSE of parents, especially fathers, is
      recommended.

PMID- 27699739
TI  - [The Decision-Making Processes in Taiwanese Women With Repeat Caesarean
      Deliveries].
AB  - BACKGROUND: Repeat caesarean delivery (RCD) ranks as the top reason for the high
      caesarean rates in Taiwan. More than 90% of Taiwanese women who have had a
      previous caesarean delivery chose RCD following their next pregnancy. PURPOSE: To
      explore the decision-making processes regarding RCD in Taiwanese women. METHODS:
      A qualitative approach with grounded theory was used to conduct this research.
      Participants were recruited from a private medical centre in northern Taiwan.
      Methods of data collection include in-depth interviews, observation, and field
      notes. Constant comparative analytical techniques were employed for data
      analysis. RESULTS: A total of 16 women chose RCD. Ensuring the well-being of
      mother and fetus was the core theme. Women's decisions were influenced by both
      internal factors (previous negative experience of birth, concern about uterine
      rupture, fixing the scar of previous caesarean and current pregnancy situation)
      and external factors (obstetrician's recommendation, the experience of female
      significant others, an inaccurate information from internet and the unconditional
      financial coverage from Health National Insurance). Decision-making processes
      involved searching information regarding mode of birth, evaluating vaginal birth
      risk, trusting obstetricians' professional judgment, and a lack of progress
      during the course of labour. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The well
      being of mother and fetus is the major concern affecting mothers' decisions
      regarding RCD. The majority of Taiwanese women participate passively in the
      decision-making process regarding their options for mode of birth. In the present
      study, women choices were primarily guided by reducing the risk of uterine
      rupture. Hospitals should reduce unnecessary induction interventions.
      Obstetricians should inform women of the risks and benefits of various birth
      modes. The government could establish a website that provides a clear explanation
      of the criteria for the government to financially cover the costs of RCD in order
      to assist women to make optimal birth choices.

PMID- 27699740
TI  - [The Perspectives and Expectations of New Nursing Graduates Regarding the
      Hospital-Based Nursing Students Scholarship].
AB  - BACKGROUND: The hospital-based scholarship is a relatively recent incentive used
      by hospitals to recruit new nursing graduates. Few studies have explored the
      impact of these scholarship programs on hospital recruitment. PURPOSE: To explore
      the perspectives and expectations of new nursing graduates on the application of
      a hospital-based scholarship for nursing students. METHODS: This study used a
      qualitative research approach. Purposive sampling was used to recruit 20 new
      nursing graduates from one university in northern Taiwan in 2013. Content
      analysis was applied to analyze the data. RESULTS: Two themes were identified by
      participants who had applied for a hospital-based scholarship: "aspire to be a
      nursing-scholarship recipient and work towards this aspiration" and "look forward
      to receiving a nursing-scholarship and imagine possible features of the future
      life." One theme was identified by participants who had not applied for a
      hospital-based scholarship: "agree with the policy of hospital-based scholarship
      but resist the restrictions on their life." CONCLUSIONS / IMPLICATIONS FOR
      PRACTICE: Although both groups agreed that the scholarship program helped relieve
      financial stresses, participants who had applied for the scholarship tended to
      hold positive and aggressive attitudes towards the nursing scholarship.
      Conversely, participants who had not applied for the scholarship did so due to
      the perceived conflicts between the scholarship and their career plans. It is
      recommended to consider providing career-planning assistance to new graduates and
      to arrange that students who sign a scholarship contract have their clinical
      practice in their working unit in order to improve adaptation.

PMID- 27699742
TI  - [Comparison of Stages of Physical Activity Among Nurses, Physicians, and Allied
      Healthcare Professionals].
AB  - BACKGROUND: Despite the fact that regular physical activity is known to improve
      physical health and reduce absenteeism and perceived job strain, healthcare
      professionals currently perform inadequate physical activity. PURPOSE: To
      understand and compare the differences in stages of physical activity among
      nurses, physicians, and allied healthcare professionals. METHODS: A cross
      sectional questionnaire was used to survey nurses, physicians, and allied
      healthcare professionals who worked at four branches of a hospital in Taiwan.
      Data were collected using the physical activity stage of change questionnire.
      Data were analyzed using descriptive analysis, Chi-square test of homogeneity of
      proportions and a posteriori comaparisons, and multinominal logistic regression
      analysis. RESULTS: Of the 3,260 questionnaires administrated, 2,001 valid
      questionnaires were returned for an effective response rate of 61.4%. In total,
      1,497 (74.8%) of the nurses, 241 (12.0%) of the physicians, and 263 (13.1%) of
      the allied healthcare professionals completed the questionnaire. The results
      revealed that most of the physicans and allied healthcare professionals were in
      the preparation stage, while most of the nurses were in the precontemplation
      stage. Multinominal logistic regression analyses showed that, using the
      precontemplation stage as a reference value, the odds of being in the
      contemplation stage were lower among participants who were nurses or male or who
      had a master's or doctoral degree (p < .05). Further, the odds of being in the
      preparation stage were lower among nurses (p < .01). The odds of being in the
      maintenance stage were higher among participants that: lived in the Taitung area,
      were male, or were single (p < .01). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The
      findings provide valuable references for future hospital leaders to develop
      effective individual physical activity programs for healthcare professionals.

PMID- 27699741
TI  - [The Association Between Multimorbidity and Medication Non-Adherence in Elderly
      With Hypertension in Western China].
AB  - BACKGROUND: The prevalence of hypertension increases with aging. Medication non
      adherence is an important reason for the failure to control hypertension
      effectively, which increases the risks of cardiovascular and cerebrovascular
      incidents and of mortality. Multimorbidity is common among the elderly and has
      become a WHO-supported priority of research worldwide. While recent research
      suggests an association between multimorbidity and medication non-adherence, the
      results are not yet conclusive. PURPOSE: The present study describes the
      condition of medication non-adherence and multimorbidity among a population of
      elderly with hypertension in western China and explores the extent of the
      association between multimorbidity and medication non-adherence. METHODS: A cross
      sectional design with multi-stage sampling was used to recruit 1,316 elderly with
      hypertension from nine community health centers in the cities of Chengdu,
      Chongqing, and Urumqi. Data were collected using the study questionnaire and
      analyzed using the mean, percentage, independent samples t test, Chi-square test,
      Kruskal-Wallis H test, and binary logistic regression. RESULTS: The prevalence of
      medication non-adherence was 28.7%, and the prevalence of multimorbidity was
      77.0%. Binary logistic regression analysis found the number of comorbidities to
      be a predictor of antihypertensive drug non-adherence, with those elderly with
      three (OR = 1.742, 95% CI [1.017, 2.984], four (OR = 2.601, 95% CI [1.489, 4.544]
      and more than five (OR = 3.262, 95% CI [1.839, 5.788] chronic conditions at
      significantly higher risk of non-adherence than their peers with no
      comorbidities. Other associated factors included poor health behaviors (OR =
      1.715, 95% CI [1.263, 2.330] and region of residence. CONCLUSIONS: A positive
      association was found between medication non-adherence and the number of
      comorbidities in elderly with hypertension. This suggests the need for closer
      monitoring of the antihypertensive-drug prescription adherence of elderly with
      multiple chronic conditions and for further research to explore the measures that
      are necessary to improve medication adherence in this population.

PMID- 27699743
TI  - [Preventing Facial Pressure Injuries in Patients Who Use Noninvasive Positive
      Pressure Ventilators: The Efficiency of Dressings].
AB  - BACKGROUND: Noninvasive positive pressure ventilation (NPPV) provides ventilation
      without tracheal intubation. Facial pressure injury is a recognized complication
      of this technique, making the prevention of facial pressure injuries an important
      issue for NPPV patients. PURPOSE: The present study compared the effects of foam
      dressing and hydrocolloid dressing in preventing facial pressure injuries in NPPV
      patients. METHODS: A randomized clinical trial was used to evaluate participants
      that were referred from the intensive care unit of a medical center in eastern
      Taiwan. Participants were randomized into two groups: the foam dressing group and
      the hydrocolloid dressing group. Statistics used in analysis were: analysis mean,
      standard deviation, chi-square, independent t-test, and the generalized
      estimating equation. RESULTS: Sixty participants were enrolled as participants.
      The incidence rate of facial pressure injury was 11.7% (7/60). No significant
      difference was found between the two groups in terms of duration of NPPV use,
      incidence of facial pressure injury, and occurrence time of facial pressure
      injury. However, the hydrocolloid dressing group had a higher usage amount than
      the foam dressing group (p < .05). CONCLUSIONS: Foam and hydrocolloid dressings
      are both helpful in preventing facial pressure injury when used in conjunction
      with regular skin assessments.

PMID- 27699744
TI  - [Factors Related to the Unplanned 90-Day Readmission Rate Among Elderly at a
      Geriatric Medicine Center].
AB  - BACKGROUND: Unplanned readmissions increase healthcare utilization rates and
      healthcare costs. The Taiwan Healthcare Indicator Series regards the rate of
      hospital readmission as an important indicator of inpatient-care quality. The
      elderly face a higher risk of unplanned readmission due to elderly-specific
      health and disease characteristics such as deteriorating body functions and the
      relatively high incidence of complications after the treatment of acute diseases.
      PURPOSE: To explore the factors that relate to the unplanned readmission of
      elderly within 90 days of discharge at a geriatric medical center. METHODS: We
      retrospectively reviewed the medical records of inpatients aged >=65 years who
      had been admitted between January 2013 and December 2014. Related factors that
      affected the rate of unplanned readmission within 90 days of discharge were
      screened and analyzed using the chi-squared test and logistic regression
      analysis. RESULTS: The 90-day unplanned readmission rate was 20.3%. Factors that
      were found to relate to unplanned readmissions were: emergency room admission
      (88.7%), lack of regular outpatient follow-up (60.4%), cerebrovascular incidents
      (43.4%), osteoporosis (32.1%), gastrointestinal diseases (45.3%), and a
      hemoglobin level < 10.0 mg/dL (35.8%). CONCLUSIONS / IMPLICATIONS FOR PRACTICE:
      The results of the present study may help the healthcare team better understand
      the factors that affect unplanned readmission in the elderly. We suggest that
      these teams provide timely health education for elderly, integrative healthcare
      for chronic diseases, and appropriate nutritional supplements in order to reduce
      unplanned readmissions.

PMID- 27699745
TI  - [Community Integrated Support Centers: The Experience of Hachioji, Tokyo, Japan].
AB  - The proportion of elderly in Taiwan reached 11.99% of the population in 2014.
      Further, Taiwan is expected to become a super-aged society, as defined by the
      United Nations, in 2025. Elderly and long-term care needs have increased
      dramatically and long-term care (LTC) has become an increasingly important focus
      of policymaking. Japan, already a super-aged society, enacted LTC insurance in
      2000 and has since implemented comprehensive LTC services nationwide. This
      article describes the evolution of the LTC insurance plan in Japan and the
      function of the Community Inclusive Care System. The latter integrates medical
      care, homecare services, LTC services, living support, and Community Integrated
      Support Centers with public-health nurses, social workers, and care managers in
      order to facilitate the construction of services that enhance aging in place. The
      authors hope that learning from Japan's experience in developing LTC will
      facilitate the future development of LTC services in Taiwan.

PMID- 27699746
TI  - [Introduction to Integrated Diabetes Care].
AB  - Diabetes is a huge problem that has been recognized as an important healthcare
      issue by most national governments. Diabetes affects patients not only in terms
      of physical health but also in terms of mental health. Furthermore, the medical
      costs that are associated with diabetes are considerable. Many countries have
      developed integrated care models for the treatment of diabetes and pay particular
      attention to assisting patients that require complicated care. Evidence from
      empirical studies shows that the integrated care of diabetes reduces
      complications, increases patients' health literacy, and decreases medical costs.
      Accordingly, integrated care has been applied to the treatment and care of
      diabetes patients. In the integrated care model, patients not only receive
      multidisciplinary care during hospitalization but also receive medical services
      after their return to the community. There has been a dearth of scholarly
      discussions in Taiwan related to the integrated care of diabetes. Therefore, we
      present in this paper the concept of integrated diabetes care and the role of the
      advanced practice nurse (APN) in the multidisciplinary model. It is hoped that
      this introduction provides practical insights for healthcare professionals into
      the essence of integrated care.

PMID- 27699747
TI  - [New Hope for HER2-Positive Metastatic Breast Cancer Treatment: Trastuzumab
      Emtansine (T-DM1) From the Perspective of Nursing Care].
AB  - Human epidermal growth factor receptor (HER2)-positive breast cancer is
      associated with a more aggressive disease and poor prognosis. The development of
      trastuzumab, a HER2-targeted agent, has changed the paradigm of HER2-positive
      breast cancer treatment and improved survival rates dramatically. However,
      metastatic HER2-positive breast cancer patients eventually develop resistance to
      this treatment regimen eventually. A new anti-HER2 antibody-drug conjugate,
      Trastuzumab emtansine (T-DM1), has been shown to improve treatment efficacy.
      However, side effects that differ from trastuzumab, including thrombocytopenia,
      liver dysfunction, fatigue, cardiotoxicity, pneumonitis, and peripheral
      neuropathy, may occur. Clinical nurses must understand the mechanism of this new
      agent and be aware of the symptoms and signs related to its side effects.
      Furthermore, clinical nurses should understand the varying degrees of these side
      effects, their probable causes, and the potential approaches to their management.
      Finally, clinical nurses must understand how to administer this agent in order to
      ensure patient safety. Understanding the side effects of T-DM1 and their
      management will help elevate nursing quality and caring efficacy.

PMID- 27699748
TI  - [Nursing Experience With a Patient With Gastrostomy Leakage Resulting in Moisture
      Associated Skin Damage].
AB  - Leakage is a common complication of gastrostomy. Exposure of the skin surrounding
      the gastrostomy tube to moisture or chemical irritants may cause moisture
      associated skin damage (MASD) and seriously affect the patient's quality of life.
      This case study describes a nursing experience with gastrostomy leakage that
      resulted in MASD. An assessment conducted from July 29, 2015 to August 20, 2015
      revealed that heavy gastronomy leakage had caused extensive skin erosion,
      ulceration, hyperplasia, and superficial infection. Simultaneously, the patient
      was required to conduct complex stoma care, which resulted in physical and
      psychological exhaustion. Changes in traditional tube and wound care were
      discussed on multiple occasions with an interdisciplinary healthcare team. Based
      on the evidence-based literature, we provide gastrostomy and MASD management
      strategies. Through team collaboration, we prevented gastric contents from
      contacting the patient's skin directly, improved patient comfort, controlled
      effluent and skin infections, maintained fluid and electrolyte balances, and acce
      lerated the healing of the damaged skin. We recommend that healthcare
      professionals caring for patients with gastrostomy leakage be provided with early
      skin protection programs to learn the standard methods for identifying and
      correcting leakage factors, containing effluent, and adequately stabilizing the
      gastrostomy tube in order to reduce the impact on the patient's quality of life.
      In addition, patient education on tube and skin care should be provided to
      prevent the reoccurrence of complications.

PMID- 27699749
TI  - [Appraisal of the formation of afterimages by means of a new computer application
      in patients with demyelinating optic neuropathies].
AB  - INTRODUCTION: The perception of colour is one of the visual functions affected by
      optic neuritis. Most of the tests currently available for evaluating dichromatism
      are based on assessing the hue, but no clinical studies have been conducted to
      investigate the formation of afterimages on the retina of these patients. AIMS:
      To evaluate the dichromatism acquired in demyelinating optic neuritis by means of
      the formation of afterimages on the retina. SUBJECTS AND METHODS: This is an
      observation-based, cross-sectional, case-control study. The cases are patients
      with at least one bout of optic neuritis and confirmed multiple sclerosis. A
      healthy age- and sex-paired control was selected for each case. The main variable
      is the capacity to see afterimages after saturation of the retinal photoreceptor
      cells. A specific computer application was developed to evaluate this phenomenon.
      RESULTS: The sample consisted of 30 cases and 30 controls (63% females; mean age:
      33 years; range: 18-48 years). The cases showed less probability of seeing the
      afterimage (36.6% of the cases, while none of the controls failed to see an
      afterimage) and, if it was seen, it remained for less time. The ROC curve shows a
      sensitivity of 86.3% and a specificity of 83.3%. The odds ratio was 5 (95%
      confidence interval: 2.21-11.3) for the probability of seeing the afterimage in
      controls versus cases. CONCLUSIONS: Patients with at least one episode of optic
      neuritis presented a lower capacity to observe afterimages. The test is therefore
      useful in the assessment and follow-up of functional damage in demyelinating
      optic neuropathies.

PMID- 27699750
TI  - [Frequency of single nucleotide polymorphisms and alpha-synuclein haplotypes
      associated with sporadic Parkinson's disease in the Mexican population].
AB  - INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disease
      which begins in adulthood. Its incidence in Mexico is estimated to be 40-50 cases
      per 100,000 inhabitants/year and is the fourth reason for medical care in the
      National Institute of Neurology and Neurosurgery. The protein alpha-synuclein,
      SNCA, plays a key role in the pathology of PD, and its polymorphisms have been
      associated with an increased risk of developing the disease. AIM: To evaluate the
      risk of PD represented by the polymorphisms rs2619364, rs2619363, rs2736990,
      rs7684318, rs17016074, rs356219, rs356220 and rs356203 of SNCA in a sample of
      Mexican subjects. SUBJECTS AND METHODS: Altogether 171 patients diagnosed with PD
      and 171 gender- and age-paired controls were assessed by means of real-time
      polymerase chain reaction, and a statistical analysis was performed to determine
      the association between the polymorphisms and the disease. RESULTS: The SNCA
      variants rs356220, rs356203, rs7684318 and rs2736990 were associated with the
      disease and form two haplotypes with a high risk of developing sporadic PD in the
      Mexican population. CONCLUSIONS: Variations in SNCA are a risk factor for the
      development of PD and can act as specific genetic biomarkers as a diagnostic
      support tool in sporadic PD for Mexican mestizo patients.

PMID- 27699751
TI  - [Diagnostic, prognostic and therapeutic implications of transcranial color-coded
      duplex sonography in acute ischemic stroke: TIBI and COGIF scores validation].
AB  - AIM: To describe the information provided by transcranial color-coded duplex
      (TCCD) sonography for therapeutic decision-making in patients with acute ischemic
      stroke and to analyze the relationship between TCCD findings and the severity and
      prognosis of stroke. PATIENTS AND METHODS: TCCD performed within the six first
      hours after an acute ischemic stroke were analyzed in our institution. The
      presence of an arterial occlusion and its location were collected using TIBI
      (Thrombolysis in Brain Ischemia) and COGIF (Consensus on Grading Intracranial
      Flow Obstruction) criteria. Arterial recanalization within 24 hours after stroke
      was determined using TIBI and COGIF criteria. Favorable functional outcome was
      defined as a modified Rankin scale from 0 to 2 at three months. RESULTS: TCCD was
      performed in 104 patients, 85 were treated with intravenous thrombolysis.
      Arterial occlusion was detected in 79.8% of patients. The detection of arterial
      occlusion with TCCD allowed the selection for endovascular treatment in 23.1% of
      patients. Arterial occlusion was associated with a higher severity of stroke.
      Recanalization was detected in 44.1% using TIBI and 45.8% according to COGIF
      criteria. 80.8% of recanalized patients and only 39.5% of not recanalized had a
      favorable functional outcome at three months. Recanalization rate depended on the
      location of arterial occlusion. CONCLUSION: TCCD is a useful technique for the
      detection and location of arterial occlusion. It provides valuable prognostic
      information and allows selecting patients for endovascular recanalizing
      therapies. TIBI and COGIF scores provide a comparable information.

PMID- 27699753
TI  - [Early pharmacologic treatment with botulinum toxin A in post-stroke spasticity:
      consensus evidence-based recommendations].
AB  - Spasticity is a common complication that occurs in those patients that have
      suffered a stroke. To identify those patients at high risk of having post-stroke
      spasticity and to start treatment at early stages would probably benefit the
      patient. The key aspects in the early management of post-stroke spasticity were
      review and the clinical implications and strength of evidences were also
      considered. The document drafted by the study coordinators was subsequently
      reviewed and then a validated document was developed. The experts recommend
      defining early treatment of spasticity as one that begins before the first three
      months after stroke. The panel considers very important to identify the risk
      factors associated with the onset of spasticity, since this might reduce its
      impact. Additionally, the most common conditions subsidiaries of early treatment
      of both upper and lower limb are defined. The panel recommends that the treatment
      with botulinum toxin A must only be given by specialists with experience in
      diagnosis and management of spasticity. In conclusion, the treatment of focal
      spasticity in the first three months after stroke is indicated in certain
      situations. These recommendations help to standardize the early management of
      post-stroke spasticity, with the consequent support to clinicians and patients.

PMID- 27699752
TI  - [RIT1: a novel gene associated with Noonan syndrome].
AB  - INTRODUCTION: Noonan syndrome is the most frequent of the congenital group of
      malformation syndromes caused by germline mutations that encode components of the
      RAS/MAPK pathway, termed RASopathies, one of the most frequent congenital genetic
      disorders in the clinical practice. Recently RIT1 mutations have been reported in
      patients with Noonan syndrome. CASE REPORT: A 7 years-old girl with a clinical
      diagnosis of Noonan syndrome, and with a hypertrophic cardiomyopathy included in
      her clinical manifestations, where a de novo heterozygous, probably pathogenic,
      novel mutation in RIT1, c.295T>C (p.Phe99Leu), has been identified. CONCLUSIONS:
      RIT1 shares homology with other RAS proteins and the expression of mutant alleles
      demonstrates a gain-of-function effect supporting a causative role in Noonan
      syndrome pathogenesis. Data suggest that the frequency of RIT1 mutations can be
      estimated as 3-5% in Noonan syndrome patients. These cases compared with Noonan
      patients harboring mutations in other genes are characterized by high frequency
      of prenatal abnormalities and hypertrophic cardiomyopathy, and lower frequencies
      of short stature and pectus abnormalities. We emphasize the importance of the
      novel identified genes in order to be included in the diagnostic panels.

PMID- 27699754
TI  - [Tarantism in Spain in the eighteen century: latrodectism and suggestion].
AB  - INTRODUCTION: Tarantism is the disease caused by the bite of the tarantula, in
      which the music tarantella triggers an involuntary dance. It is known in Italy
      since the sixteenth century. AIM: To analyze the tarantism reported in Spain at
      the end of the eighteenth century, with special attention to its neurological
      aspects, and to propose its medical and psychopathological explanation.
      DEVELOPMENT: An epidemic of people affected by the tarantula bite occurred in
      Spain in 1782. Spanish doctors described appropriately the clinical effects,
      identical to those produced by the bite of the spider black widow (Latrodectus
      tredecimguttatus), which was at that time identified as a tarantula. The cases
      reported by Francisco Xavier Cid cured with the involuntary dance triggered by
      the tarantella, as was described in Italy since the sixteenth century. Our
      interpretation is that this curative effect of dance in Spain was induced by
      suggestion. In Spanish patients there were no behavioral disturbances, periodic
      recurrences or collective involvement as those reported by Italian authors, which
      suggest an hysterical phenomenon, probably a continuation of the dancing mania of
      the Middle Age. CONCLUSIONS: Tarantism reported in Spain in the eighteenth
      century includes two different phenomena: the systemic symptoms produced by the
      tarantula bite, which is actually latrodectism, and the curative effect of the
      tarantella, explained by suggestion. The psychiatric disturbances, with a
      hysterical nature, falsely associated to the tarantula bite, observed in Italy,
      were not present among the Spanish cases of tarantism in the eighteenth century.

PMID- 27699755
TI  - Atypical neuropathy in MPO-ANCA small vessel vasculitis.

PMID- 27699756
TI  - [Urgent stroke care in hospitals with a stroke unit. Quick Project].

PMID- 27699757
TI  - [Urgent stroke care in hospitals with a stroke unit. Quick Project. Reply].

PMID- 27699758
TI  - [Healthy sleep: evidence and guidelines for action. Official document of the
      Spanish Sleep Society].
AB  - One of the main objectives of the Spanish Sleep Society is to promote healthy
      sleep in both the general population and in health professionals. This document
      aims to conduct a review of the current scientific literature on sleep habits
      that can serve as the basis on which to establish a set of general
      recommendations, regarding healthy sleep, for use by the general population in
      Spain as well as to identify the main challenges faced by research into sleep
      habits. The document has been developed by a multidisciplinary team made up of
      members of the Spanish Sleep Society who are experts in paediatric sleep
      medicine, clinical neurophysiology, pulmonology, neurology, chronobiology,
      physiology and psychology. The existing scientific literature dealing with sleep
      habits in the general population was reviewed, and the following aspects were
      addressed: the current state of sleep habits in the Spanish population; a generic
      review of the optimum number of hours of sleep; the impact of the environmental
      setting (noise, temperature, illumination, etc.), hours of sleep, diet and sport,
      together with several specific sections for children and teenagers, shift-workers
      and drivers of different vehicles. The conclusions from all the aspects addressed
      in this document have resulted in a set of final general recommendations that
      will serve as a guide for the general population and health professionals.
      Likewise, the principal environmental challenges and future lines of research are
      also discussed.

PMID- 27699759
TI  - Severe sepsis in the ICU is often missing in hospital discharge codes.
AB  - BACKGROUND: Different International Classification of Diseases (ICD)-based code
      abstraction strategies have been used when studying the epidemiology of severe
      sepsis. The aim of this study was to compare three previously used ICD code
      abstraction strategies to the American College of Chest Physicians/Society of
      Critical Care Medicine (ACCP/SCCM) consensus criteria for severe sepsis, in a
      setting of intensive care patients. METHODS: All patients (>= 18 years of age)
      with severe sepsis according to the ACCP/SCCM criteria registered in the Swedish
      Intensive Care Registry (2005-2009) were included in the study. Using the Swedish
      National Patient Register, we investigated whether these patients fulfilled an
      ICD code compilation for severe sepsis at hospital discharge. RESULTS: Overall,
      9271 patients with severe sepsis were registered in the Swedish Intensive Care
      Registry. A majority of these patients (55.4%) were discharged from the hospital
      with ICD codes that did not correspond to any of the ICD code compilations. A
      minority of patients (10.3%) were discharged with ICD codes corresponding to all
      three code abstraction strategies applied. Overall, the proportion of patients
      discharged with ICD codes corresponding to the criteria of Angus et al. was
      15.1%, to the criteria of Flaatten was 39.8%, and to the criteria of Martin et
      al. was 16.0%. CONCLUSIONS: A majority of patients with severe sepsis according
      to the ACCP/SCCM criteria were not discharged with ICD codes corresponding to the
      ICD code abstraction strategies; thus, the abstraction strategies did not
      identify the correct patients.

PMID- 27699760
TI  - Intensity of continuous renal replacement therapy for acute kidney injury.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common condition among patients in
      intensive care units (ICU), and is associated with substantial morbidity and
      mortality. Continuous renal replacement therapy (CRRT) is a blood purification
      technique used to treat the most severe forms of AKI but its effectiveness
      remains unclear. OBJECTIVES: To assess the effects of different intensities
      (intensive and less intensive) of CRRT on mortality and recovery of kidney
      function in critically ill AKI patients. SEARCH METHODS: We searched Cochrane
      Kidney and Transplant's Specialised Register to 9 February 2016 through contact
      with the Information Specialist using search terms relevant to this review.
      Studies contained in the Specialised Register are identified through search
      strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching
      conference proceedings; and searching the International Clinical Trials Register
      (ICTRP) Search Portal and ClinicalTrials.gov. We also searched LILACS to 9
      February 2016. SELECTION CRITERIA: We included all randomised controlled trials
      (RCTs). We included all patients with AKI in ICU regardless of age, comparing
      intensive (usually a prescribed dose >=35 mL/kg/h) versus less intensive CRRT
      (usually a prescribed dose < 35 mL/kg/h). For safety and cost outcomes we planned
      to include cohort studies and non-RCTs. DATA COLLECTION AND ANALYSIS: Data were
      extracted independently by two authors. The random-effects model was used and
      results were reported as risk ratios (RR) for dichotomous outcomes and mean
      differences (MD) for continuous outcomes, with 95% confidence intervals (CI).
      MAIN RESULTS: We included six studies enrolling 3185 participants. Studies were
      assessed as being at low or unclear risk of bias. There was no significant
      difference between intensive versus less intensive CRRT on mortality risk at day
      30 (5 studies, 2402 participants: RR 0.88, 95% CI 0.71 to 1.08; I2 = 75%; low
      quality of evidence) or after 30 days post randomisation (5 studies, 2759
      participants: RR 0.92, 95% CI 0.80 to 1.06; I2 = 65%; low quality of evidence).
      There were no significant differences between intensive versus less intensive
      CRRT in the numbers of patients who were free of RRT after CRRT discontinuation
      (5 studies, 2402 participants: RR 1.12, 95% CI 0.91 to 1.37; I2 = 71%; low
      quality of evidence) or among survivors at day 30 (5 studies, 1415 participants:
      RR 1.03, 95% CI 0.96 to 1.11; I2 = 69%; low quality of evidence) and day 90 (3
      studies, 988 participants: RR 0.98, IC 95% 0.94 to 1.01, I2 = 0%; moderatequality
      of evidence). There were no significant differences between intensive and less
      intensive CRRT on the number of days in hospital (2 studies, 1665 participants):
      MD -0.23 days, 95% CI -3.35 to 2.89; I2 = 8%; low quality of evidence) and the
      number of days in ICU (2 studies, 1665 participants: MD -0.58 days, 95% CI -3.73
      to 2.56, I2 = 19%; low quality of evidence). Intensive CRRT increased the risk of
      hypophosphataemia (1 study, 1441 participants: RR 1.21, 95% CI 1.11 to 1.31; high
      quality evidence) compared to less intensive CRRT. There was no significant
      differences between intensive and less intensive CRRT on numbers of patients who
      experienced adverse events (3 studies, 1753 participants: RR 1.08, 95% CI 0.73 to
      1.61; I2 = 16%; moderate quality of evidence). In the subgroups analysis by
      severity of illness and by aetiology of AKI, intensive CRRT would seem to reduce
      the risk mortality (2 studies, 531 participants: RR 0.73, 95% CI 0.61 to 0.88; I2
      = 0%; high quality of evidence) only in the subgroup of patients with post
      surgical AKI. AUTHORS' CONCLUSIONS: Based on the current low quality of evidence
      identified, more intensive CRRT did not demonstrate beneficial effects on
      mortality or recovery of kidney function in critically ill patients with AKI.
      There was an increased risk of hypophosphataemia with more intense CRRT.
      Intensive CRRT reduced the risk of mortality in patients with post-surgical AKI.

PMID- 27699762
TI  - Inferior epigastric artery: Prevention of injury.

PMID- 27699761
TI  - Strategies to improve the implementation of healthy eating, physical activity and
      obesity prevention policies, practices or programmes within childcare services.
AB  - BACKGROUND: Despite the existence of effective interventions and best-practice
      guideline recommendations for childcare services to implement policies, practices
      and programmes to promote child healthy eating, physical activity and prevent
      unhealthy weight gain, many services fail to do so. OBJECTIVES: The primary aim
      of the review was to examine the effectiveness of strategies aimed at improving
      the implementation of policies, practices or programmes by childcare services
      that promote child healthy eating, physical activity and/or obesity prevention.
      The secondary aims of the review were to:1. describe the impact of such
      strategies on childcare service staff knowledge, skills or attitudes;2. describe
      the cost or cost-effectiveness of such strategies;3. describe any adverse effects
      of such strategies on childcare services, service staff or children;4. examine
      the effect of such strategies on child diet, physical activity or weight status.
      SEARCH METHODS: We searched the following electronic databases on 3 August 2015:
      the Cochrane Central Register of Controlled trials (CENTRAL), MEDLINE, MEDLINE In
      Process, EMBASE, PsycINFO, ERIC, CINAHL and SCOPUS. We also searched reference
      lists of included trials, handsearched two international implementation science
      journals and searched the World Health Organization International Clinical Trials
      Registry Platform (www.who.int/ictrp/) and ClinicalTrials.gov
      (www.clinicaltrials.gov). SELECTION CRITERIA: We included any study (randomised
      or non-randomised) with a parallel control group that compared any strategy to
      improve the implementation of a healthy eating, physical activity or obesity
      prevention policy, practice or programme by staff of centre-based childcare
      services to no intervention, 'usual' practice or an alternative strategy. DATA
      COLLECTION AND ANALYSIS: The review authors independently screened abstracts and
      titles, extracted trial data and assessed risk of bias in pairs; we resolved
      discrepancies via consensus. Heterogeneity across studies precluded pooling of
      data and undertaking quantitative assessment via meta-analysis. However, we
      narratively synthesised the trial findings by describing the effect size of the
      primary outcome measure for policy or practice implementation (or the median of
      such measures where a single primary outcome was not stated). MAIN RESULTS: We
      identified 10 trials as eligible and included them in the review. The trials
      sought to improve the implementation of policies and practices targeting healthy
      eating (two trials), physical activity (two trials) or both healthy eating and
      physical activity (six trials). Collectively the implementation strategies tested
      in the 10 trials included educational materials, educational meetings, audit and
      feedback, opinion leaders, small incentives or grants, educational outreach
      visits or academic detailing. A total of 1053 childcare services participated
      across all trials. Of the 10 trials, eight examined implementation strategies
      versus a usual practice control and two compared alternative implementation
      strategies. There was considerable study heterogeneity. We judged all studies as
      having high risk of bias for at least one domain.It is uncertain whether the
      strategies tested improved the implementation of policies, practices or
      programmes that promote child healthy eating, physical activity and/or obesity
      prevention. No intervention improved the implementation of all policies and
      practices targeted by the implementation strategies relative to a comparison
      group. Of the eight trials that compared an implementation strategy to usual
      practice or a no intervention control, however, seven reported improvements in
      the implementation of at least one of the targeted policies or practices relative
      to control. For these trials the effect on the primary implementation outcome was
      as follows: among the three trials that reported score-based measures of
      implementation the scores ranged from 1 to 5.1; across four trials reporting the
      proportion of staff or services implementing a specific policy or practice this
      ranged from 0% to 9.5%; and in three trials reporting the time (per day or week)
      staff or services spent implementing a policy or practice this ranged from 4.3
      minutes to 7.7 minutes. The review findings also indicate that is it uncertain
      whether such interventions improve childcare service staff knowledge or attitudes
      (two trials), child physical activity (two trials), child weight status (two
      trials) or child diet (one trial). None of the included trials reported on the
      cost or cost-effectiveness of the intervention. One trial assessed the adverse
      effects of a physical activity intervention and found no difference in rates of
      child injury between groups. For all review outcomes, we rated the quality of the
      evidence as very low. The primary limitation of the review was the lack of
      conventional terminology in implementation science, which may have resulted in
      potentially relevant studies failing to be identified based on the search terms
      used in this review. AUTHORS' CONCLUSIONS: Current research provides weak and
      inconsistent evidence of the effectiveness of such strategies in improving the
      implementation of policies and practices, childcare service staff knowledge or
      attitudes, or child diet, physical activity or weight status. Further research in
      the field is required.

PMID- 27699763
TI  - Has the twin rate after in vitro fertilisation really decreased in Australia?

PMID- 27699764
TI  - Twinning: Double, double, toil and trouble?

PMID- 27699765
TI  - Non-nutritive sucking for increasing physiologic stability and nutrition in
      preterm infants.
AB  - BACKGROUND: Non-nutritive sucking (NNS) is used during gavage feeding and in the
      transition from gavage to breast/bottle feeding in preterm infants to improve the
      development of sucking behavior and the digestion of enteral feedings.
      OBJECTIVES: To assess the effects of non-nutritive sucking on physiologic
      stability and nutrition in preterm infants. SEARCH METHODS: We used the standard
      search strategy of the Cochrane Neonatal Review group to search the Cochrane
      Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), MEDLINE via
      PubMed (1966 to 25 February 2016), Embase (1980 to 25 February 2016), and CINAHL
      (1982 to 25 February 2016). We also searched clinical trials databases,
      conference proceedings, and the reference lists of retrieved articles for
      randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials
      and quasi-randomised trials that compared non-nutritive sucking versus no
      provision of non-nutritive sucking in preterm infants. We excluded cross-over
      trials. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial
      eligibility and risk of bias and undertook data extraction independently. We
      analysed the treatment effects in the individual trials and reported mean
      differences (MD) for continuous data, with 95% confidence intervals (CIs). We
      used a fixed-effect model in meta-analyses. We did not perform subgroup analyses
      because of the small number of studies related to the relevant outcomes. We used
      the GRADE approach to assess the quality of evidence. MAIN RESULTS: We identified
      12 eligible trials enrolling a total of 746 preterm infants. Meta-analysis,
      though limited by data quality, demonstrated a significant effect of NNS on
      transition from gavage to full oral feeding (MD -5.51 days, 95% CI -8.20 to 
      2.82; N = 87), transition from start of oral feeding to full oral feeding (MD 
      2.15 days, 95% CI -3.12 to -1.17; N = 100), and the length of hospital stay (MD 
      4.59 days, 95% CI -8.07 to -1.11; N = 501). Meta-analysis revealed no significant
      effect of NNS on weight gain. One study found that the NNS group had a
      significantly shorter intestinal transit time during gavage feeding compared to
      the control group (MD -10.50 h, 95% CI -13.74 to -7.26; N = 30). Other individual
      studies demonstrated no clear positive effect of NNS on age of infant at full
      oral feeds, days from birth to full breastfeeding, rates and proportion of
      infants fully breastfeeding at discharge, episodes of bradycardia, or episodes of
      oxygen desaturation. None of the studies reported any negative outcomes. These
      trials were generally small and contained various methodological weaknesses
      including lack of blinding of intervention and outcome assessors and variability
      on outcome measures. The quality of the evidence on outcomes assessed according
      to GRADE was low to very low. AUTHORS' CONCLUSIONS: Meta-analysis demonstrated a
      significant effect of NNS on the transition from gavage to full oral feeding,
      transition from start of oral feeding to full oral feeding, and length of
      hospital stay. None of the trials reported any adverse effects. Well-designed,
      adequately powered studies using reliable methods of randomisation, concealment
      of treatment allocation and blinding of the intervention and outcome assessors
      are needed. In order to facilitate meta-analysis of these data, future research
      should involve outcome measures consistent with those used in previous studies.

PMID- 27699766
TI  - Functional impairment in Tourette syndrome: parent and child perspectives.

PMID- 27699767
TI  - Glucuronic Acid Epimerase (GLCE) Variant rs3865014 (A>G) Is Associated with BMI,
      Blood Hemoglobin, Hypertension, and Cerebrovascular Events, the TAMRISK Study.
AB  - Heparan sulfate proteoglycans modulate many physiological systems, and genes
      responsible for proteoglycan assembly and disassembly may affect their
      interaction. We sought to determine whether polymorphisms of the glucuronic acid
      epimerase (GLCE) rs3865014 and sulfatase-2 (SULF2) rs2281279, genes coding for
      enzymes participating in heparan sulfate side chain activity, associate with
      hypertension, selected cardiometabolic risk factors and cardiovascular events in
      the Tampere adult population cardiovascular risk study. A Finnish cohort of 339
      subjects with diagnosed hypertension and 441 controls was analyzed. Samples were
      genotyped for GLCE rs3865014 (A>G) and SULF2 rs2281279 (T>C) polymorphisms using
      competitive allele-specific PCR (KASP) technique. Prevalence of ischemic heart
      diseases (I20-I25) and incidence of cerebrovascular diseases (I60-I69) and
      transient cerebral ischemic attacks (TIA) (G45) were followed up until the
      subjects were on the average 60 years old. GLCE rs3865014 G allele showed
      negative association with hypertension (p = 0.022), waist circumference (p =
      0.032), BMI (p = 0.048), and positive association with hemoglobin (p = 0.029),
      low-density lipoprotein cholesterol (p = 0.031), and frequency of cerebrovascular
      events (p = 0.011). SULF2 rs2281279 showed no association with the studied
      parameters. The GLCE gene polymorphism rs3865014 appears to have biological
      relevance in human pathophysiology.

PMID- 27699768
TI  - Cross-cultural validity of standardized motor development screening and
      assessment tools: a systematic review.
AB  - AIM: To investigate whether standardized motor development screening and
      assessment tools that are used to evaluate motor abilities of children aged 0 to
      2 years are valid in cultures other than those in which the normative sample was
      established. METHOD: This was a systematic review in which six databases were
      searched. Studies were selected based on inclusion/exclusion criteria and
      appraised for evidence level and quality. Study variables were extracted.
      RESULTS: Twenty-three studies representing six motor development screening and
      assessment tools in 16 cultural contexts met the inclusion criteria: Alberta
      Infant Motor Scale (n=7), Ages and Stages Questionnaire, 3rd edition (n=2),
      Bayley Scales of Infant and Toddler Development, 3rd edition (n=8), Denver
      Developmental Screening Test, 2nd edition (n=4), Harris Infant Neuromotor Test
      (n=1), and Peabody Developmental Motor Scales, 2nd edition (n=1). Thirteen
      studies found significant differences between the cultural context and normative
      sample. Two studies established reliability and/or validity of standardized motor
      development assessments in high-risk infants from different cultural contexts.
      Five studies established new population norms. Eight studies described the cross
      cultural adaptation of a standardized motor development assessment.
      INTERPRETATION: Standardized motor development assessments have limited validity
      in cultures other than that in which the normative sample was established. Their
      use can result in under- or over-referral for services.

PMID- 27699770
TI  - Para-allopatry in hybridizing fire-bellied toads (Bombina bombina and B.
      variegata): Inference from transcriptome-wide coalescence analyses

PMID- 27699769
TI  - BAY 1125976, a selective allosteric AKT1/2 inhibitor, exhibits high efficacy on
      AKT signaling-dependent tumor growth in mouse models.
AB  - The PI3K-AKT-mTOR signaling cascade is activated in the majority of human
      cancers, and its activation also plays a key role in resistance to chemo and
      targeted therapeutics. In particular, in both breast and prostate cancer,
      increased AKT pathway activity is associated with cancer progression, treatment
      resistance and poor disease outcome. Here, we evaluated the activity of a novel
      allosteric AKT1/2 inhibitor, BAY 1125976, in biochemical, cellular mechanistic,
      functional and in vivo efficacy studies in a variety of tumor models. In in vitro
      kinase activity assays, BAY 1125976 potently and selectively inhibited the
      activity of full-length AKT1 and AKT2 by binding into an allosteric binding
      pocket formed by kinase and PH domain. In accordance with this proposed
      allosteric binding mode, BAY 1125976 bound to inactive AKT1 and inhibited T308
      phosphorylation by PDK1, while the activity of truncated AKT proteins lacking the
      pleckstrin homology domain was not inhibited. In vitro, BAY 1125976 inhibited
      cell proliferation in a broad panel of human cancer cell lines. Particularly high
      activity was observed in breast and prostate cancer cell lines expressing
      estrogen or androgen receptors. Furthermore, BAY 1125976 exhibited strong in vivo
      efficacy in both cell line and patient-derived xenograft models such as the KPL4
      breast cancer model (PIK3CAH1074R mutant), the MCF7 and HBCx-2 breast cancer
      models and the AKTE17K mutant driven prostate cancer (LAPC-4) and anal cancer
      (AXF 984) models. These findings indicate that BAY 1125976 is a potent and highly
      selective allosteric AKT1/2 inhibitor that targets tumors displaying
      PI3K/AKT/mTOR pathway activation, providing opportunities for the clinical
      development of new, effective treatments.

PMID- 27699771
TI  - Routine use of perioperative in vivo reflectance confocal microscopy of the nail
      matrix in melanonychia striata: a report of 30 cases.

PMID- 27699772
TI  - Diet and Headache: Part 2.
AB  - BACKGROUND: Comprehensive diets do not require the exclusion of a specific
      provocative food or ingredient, but regulate the quantities of core components of
      foods such as vitamins, ions, proteins, carbohydrates, and fats. OBJECTIVES: To
      review the evidence supporting the use of comprehensive diets in the prevention
      of migraine and other headache disorders and to discuss the mechanisms through
      which food, and ingredients within foods and beverages might trigger attacks of
      headache METHODS: This represents Part 2 of a narrative review of the role of
      diet in the prevention of migraine and other headache disorders. A PubMed search
      was performed with the following search terms: "folate," "vitamin D," "low fat
      diet," "omega-3 and omega-6 fatty acid diet," "ketogenic diet," "Atkins diet,"
      and "sodium." Each of these search terms was then crossreferenced with "headache"
      and "migraine" to identify relevant studies. Only studies that were written in
      English were included in this review. RESULTS: Low fat and high omega-3/low omega
      6 fatty diets decrease the frequency of attacks of migraine and/or other headache
      disorders as demonstrated in two separate randomized controlled trials. A
      ketogenic diet was more effective than a standard diet in reducing the frequency
      of migraine in a single nonrandomized clinical study. An observation study found
      that dietary consumption of folate was inversely associated with the frequency of
      migraine attacks in persons with migraine with aura that have the C variant of
      the methylene tetrahydrofolate reductase gene. The mechanisms though which diets
      may precipitate headache include their effects on neuropeptides, neuro-receptors
      and ion channels, inflammation, sympathetic nervous system, release of nitric
      oxide, vasodilation, and cerebral glucose metabolism. CONCLUSIONS: Evidence
      exists to support the use of comprehensive diets in the prevention of migraine
      and other headache disorders. However, the results of these studies should be
      considered preliminary until replicated in larger randomized controlled clinical
      trials.

PMID- 27699774
TI  - Can We Speak of Lack of Habituation in Visual Snow? A Response.

PMID- 27699775
TI  - 2016-2017 Headache Assistant Editors.

PMID- 27699776
TI  - Thunderclap Headaches.

PMID- 27699777
TI  - The Study Design Used Was Wrong But the Conclusions Made About the Drug Were
      Later Found to Be Correct.

PMID- 27699778
TI  - Headache and Celiac Disease: An Increasingly Investigated Association.

PMID- 27699779
TI  - Odorant-Triggered Migraine Attacks in a Case of Iatrogenic Olfactory Neuropathy.

PMID- 27699780
TI  - Diet and Headache: Part 1.
AB  - BACKGROUND: The role of diet in the management of the headache patient is a
      controversial topic in the headache field. OBJECTIVES: To review the evidence
      supporting the hypothesis that specific foods or ingredients within foods and
      beverages trigger attacks of headache and/or migraine and to discuss the use of
      elimination diets in the prevention of headache disorders METHODS: This
      represents part 1 of a narrative review of the role of diet in the prevention of
      migraine and other headache disorders. A PubMed search was performed with the
      following search terms: "monosodium glutamate," "caffeine," "aspartame,"
      "sucralose," "histamine intolerance syndrome," "tyramine," "alcohol,"
      "chocolate," "nitrites," "IgG elimination diets," and "gluten." Each of these
      search terms was then cross-referenced with "headache" and "migraine" to identify
      relevant studies. Only studies that were written in English were included in this
      review. RESULTS: Caffeine withdrawal and administration of MSG (dissolved in
      liquid) has the strongest evidence for triggering attacks of headache as
      evidenced by multiple positive provocation studies. Aspartame has conflicting
      evidence with two positive and two negative provocation studies. Observational
      studies provide modest evidence that gluten- and histamine-containing foods as
      well as alcohol may precipitate headaches in subgroups of patients. Two of three
      randomized controlled trials reported that an elimination diet of IgG positive
      foods significantly decreased frequency of headache/migraine during the treatment
      as compared to baseline time period. CONCLUSIONS: Certain foods, beverages, and
      ingredients within foods may trigger attacks of headache and/or migraine in
      susceptible individuals. Elimination diets can prevent headaches in subgroups of
      persons with headache disorders.

PMID- 27699781
TI  - Can We Speak of Lack of Habituation in Visual Snow?

PMID- 27699782
TI  - A Tribute to Dr. Eliova Zukerman.

PMID- 27699783
TI  - Factors that impact on the use of mechanical ventilation weaning protocols in
      critically ill adults and children: a qualitative evidence-synthesis.
AB  - BACKGROUND: Prolonged mechanical ventilation is associated with a longer
      intensive care unit (ICU) length of stay and higher mortality. Consequently,
      methods to improve ventilator weaning processes have been sought. Two recent
      Cochrane systematic reviews in ICU adult and paediatric populations concluded
      that protocols can be effective in reducing the duration of mechanical
      ventilation, but there was significant heterogeneity in study findings. Growing
      awareness of the benefits of understanding the contextual factors impacting on
      effectiveness has encouraged the integration of qualitative evidence syntheses
      with effectiveness reviews, which has delivered important insights into the
      reasons underpinning (differential) effectiveness of healthcare interventions.
      OBJECTIVES: 1. To locate, appraise and synthesize qualitative evidence concerning
      the barriers and facilitators of the use of protocols for weaning critically-ill
      adults and children from mechanical ventilation;2. To integrate this synthesis
      with two Cochrane effectiveness reviews of protocolized weaning to help explain
      observed heterogeneity by identifying contextual factors that impact on the use
      of protocols for weaning critically-ill adults and children from mechanical
      ventilation;3. To use the integrated body of evidence to suggest the
      circumstances in which weaning protocols are most likely to be used. SEARCH
      METHODS: We used a range of search terms identified with the help of the SPICE
      (Setting, Perspective, Intervention, Comparison, Evaluation) mnemonic. Where
      available, we used appropriate methodological filters for specific databases. We
      searched the following databases: Ovid MEDLINE, Embase, OVID, PsycINFO, CINAHL
      Plus, EBSCOHost, Web of Science Core Collection, ASSIA, IBSS, Sociological
      Abstracts, ProQuest and LILACS on the 26th February 2015. In addition, we
      searched: the grey literature; the websites of professional associations for
      relevant publications; and the reference lists of all publications reviewed. We
      also contacted authors of the trials included in the effectiveness reviews as
      well as of studies (potentially) included in the qualitative synthesis, conducted
      citation searches of the publications reporting these studies, and contacted
      content experts.We reran the search on 3rd July 2016 and found three studies,
      which are awaiting classification. SELECTION CRITERIA: We included qualitative
      studies that described: the circumstances in which protocols are designed,
      implemented or used, or both, and the views and experiences of healthcare
      professionals either involved in the design, implementation or use of weaning
      protocols or involved in the weaning of critically-ill adults and children from
      mechanical ventilation not using protocols. We included studies that: reflected
      on any aspect of the use of protocols, explored contextual factors relevant to
      the development, implementation or use of weaning protocols, and reported
      contextual phenomena and outcomes identified as relevant to the effectiveness of
      protocolized weaning from mechanical ventilation. DATA COLLECTION AND ANALYSIS:
      At each stage, two review authors undertook designated tasks, with the results
      shared amongst the wider team for discussion and final development. We
      independently reviewed all retrieved titles, abstracts and full papers for
      inclusion, and independently extracted selected data from included studies. We
      used the findings of the included studies to develop a new set of analytic themes
      focused on the barriers and facilitators to the use of protocols, and further
      refined them to produce a set of summary statements. We used the Confidence in
      the Evidence from Reviews of Qualitative Research (CERQual) framework to arrive
      at a final assessment of the overall confidence of the evidence used in the
      synthesis. We included all studies but undertook two sensitivity analyses to
      determine how the removal of certain bodies of evidence impacted on the content
      and confidence of the synthesis. We deployed a logic model to integrate the
      findings of the qualitative evidence synthesis with those of the Cochrane
      effectiveness reviews. MAIN RESULTS: We included 11 studies in our synthesis,
      involving 267 participants (one study did not report the number of participants).
      Five more studies are awaiting classification and will be dealt with when we
      update the review.The quality of the evidence was mixed; of the 35 summary
      statements, we assessed 17 as 'low', 13 as 'moderate' and five as 'high'
      confidence. Our synthesis produced nine analytical themes, which report potential
      barriers and facilitators to the use of protocols. The themes are: the need for
      continual staff training and development; clinical experience as this promotes
      felt and perceived competence and confidence to wean; the vulnerability of
      weaning to disparate interprofessional working; an understanding of protocols as
      militating against a necessary proactivity in clinical practice; perceived
      nursing scope of practice and professional risk; ICU structure and processes of
      care; the ability of protocols to act as a prompt for shared care and consistency
      in weaning practice; maximizing the use of protocols through visibility and ease
      of implementation; and the ability of protocols to act as a framework for
      communication with parents. AUTHORS' CONCLUSIONS: There is a clear need for
      weaning protocols to take account of the social and cultural environment in which
      they are to be implemented. Irrespective of its inherent strengths, a protocol
      will not be used if it does not accommodate these complexities. In terms of
      protocol development, comprehensive interprofessional input will help to ensure
      broad-based understanding and a sense of 'ownership'. In terms of implementation,
      all relevant ICU staff will benefit from general weaning as well as protocol
      specific training; not only will this help secure a relevant clinical knowledge
      base and operational understanding, but will also demonstrate to others that this
      knowledge and understanding is in place. In order to maximize relevance and
      acceptability, protocols should be designed with the patient profile and
      requirements of the target ICU in mind. Predictably, an under-resourced ICU will
      impact adversely on protocol implementation, as staff will prioritize management
      of acutely deteriorating and critically-ill patients.

PMID- 27699785
TI  - The new sepsis/septic shock-3 definition is just not enough - more detailed
      research is needed.

PMID- 27699784
TI  - Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic
      Nephropathy in South Indian Population.
AB  - This study reports on the association of genetic variants selected from previous
      genome-wide association studies for type 2 diabetic nephropathy in south Indians.
      Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy
      (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The
      minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant
      were significantly different between DM and DN groups (P = 0.029 and 0.016,
      respectively). A combined analysis showed that the subjects carrying the risk
      genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a
      significant association with DN with an odds ratio [adjusted for age, sex, Body
      Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30-2.30, P
      = 1.72 * 10-4 ) as compared to subjects carrying all other genotype combinations.
      This is the first study to report a significant association of the SLC12A3
      rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic
      nephropathy in south Indians.

PMID- 27699787
TI  - Arranging response requirements and the distribution of reinforcers: A brief
      review of preference and performance outcomes.
AB  - Recent research has demonstrated that some participants prefer to complete a
      larger series of responses in exchange for a longer duration of reinforcer
      access, rather than completing fewer tasks associated with smaller, but more
      frequent, reinforcer access. This review provides a summary of this line of
      research, examines variables contributing to participant preference and
      performance under different response-reinforcer arrangements, and discusses
      limitations and areas for future research.

PMID- 27699788
TI  - Temperature-dependent autoimmunity mediated by chs1 requires its neighboring TNL
      gene SOC3.
AB  - Toll/interleukin receptor (TIR)-nucleotide binding site (NB)-type (TN) proteins
      are encoded by a family of 21 genes in the Arabidopsis genome. Previous studies
      have shown that a mutation in the TN gene CHS1 activates the activation of
      defense responses at low temperatures. However, the underlying molecular
      mechanism remains unknown. To genetically dissect chs1-mediated signaling, we
      isolated genetic suppressors of chs1-2 (soc). Several independent soc mutants
      carried mutations in the same TIR-NB-leucine-rich repeat (LRR) (TNL)-encoding
      gene SOC3, which is adjacent to CHS1 on chromosome 1. Expression of SOC3 was
      upregulated in the chs1-2 mutant. Mutations in six soc3 alleles and
      downregulation of SOC3 by an artificial microRNA construct fully rescued the
      chilling sensitivity and defense defects of chs1-2. Biochemical studies showed
      that CHS1 interacted with the NB and LRR domains of SOC3; however, mutated chs1
      interacted with the TIR, NB and LRR domains of SOC3 in vitro and in vivo. This
      study reveals that the TN protein CHS1 interacts with the TNL protein SOC3 to
      modulate temperature-dependent autoimmunity.

PMID- 27699789
TI  - Capacity building for global nursing leaders: challenges and experiences.
AB  - AIM: The aim of this article is to describe our experience in operating a
      capacity-building programme, the Korea International Cooperation Project, for
      global nursing leaders from developing countries, held during the International
      Council of Nurses (ICN) Conference in 2015 in Seoul, Korea. BACKGROUND:
      Globalization points to the importance of global leadership among nursing
      leaders. In accordance with the theme of 'Global Citizen, Global Nursing' at the
      ICN conference in 2015, a capacity-building programme for nursing leaders of
      developing countries was implemented. INTRODUCTION: The global nursing leadership
      programme shared experiences during the preparation and operation of the
      conference. To prepare the programme, this paper describes selecting
      participants, working with invitation lists from 30 countries, and recruiting and
      training volunteers. The operation of the programme, orientation, organizing
      tailored programmes for participant groups, addressing unexpected issues and
      evaluating the programme are described. IMPLICATIONS FOR NURSING POLICY: ICN
      could implement capacity-building programmes for nursing leaders of developing
      countries during its ICN conference for the nursing society. A programme tailored
      for each continent with similar sociocultural backgrounds and health issues would
      provide chances for collaboration and networking. A policy to compile global
      nursing indicators should be developed. This would allow nursing leaders to learn
      about the strengths and weaknesses of global nursing and provide evidence for
      collaboration. CONCLUSION: The programme was successful in introducing and
      broadening global perspectives of participants on health and education as well as
      building a network among leaders and next-generation leaders in participating
      countries for future cooperation and collaboration.

PMID- 27699790
TI  - Comment on paraparetic Guillain-Barre syndrome: Non-demyelinating reversible
      conduction failure restricted to the lower limbs.

PMID- 27699791
TI  - Increased Amyloid Precursor Protein and Tau Expression Manifests as Key Secondary
      Cell Death in Chronic Traumatic Brain Injury.
AB  - In testing the hypothesis of Alzheimer's disease (AD)-like pathology in late
      stage traumatic brain injury (TBI), we evaluated AD pathological markers in late
      stage TBI model. Sprague-Dawley male rats were subjected to moderate controlled
      cortical impact (CCI) injury, and 6 months later euthanized and brain tissues
      harvested. Results from H&E staining revealed significant 33% and 10% reduction
      in the ipsilateral and contralateral hippocampal CA3 interneurons, increased
      MHCII-activated inflammatory cells in many gray matter (8-20-fold increase) and
      white matter (6-30-fold increased) regions of both the ipsilateral and
      contralateral hemispheres, decreased cell cycle regulating protein marker by 1.6-
      and 1-fold in the SVZ and a 2.3- and 1.5-fold reductions in the ipsilateral and
      contralateral dentate gyrus, diminution of immature neuronal marker by two- and
      onefold in both the ipsilateral and contralateral SVZ and dentate gyrus, and
      amplified amyloid precursor protein (APP) distribution volumes in white matter
      including corpus callosum, fornix, and internal capsule (4-38-fold increase), as
      well as in the cortical gray matter, such as the striatum hilus, SVZ, and dentate
      gyrus (6-40-fold increase) in TBI animals compared to controls (P's < 0.001).
      Surrogate AD-like phenotypic markers revealed a significant accumulation of
      phosphorylated tau (AT8) and oligomeric tau (T22) within the neuronal cell bodies
      in ipsilateral and contralateral cortex, and dentate gyrus relative to sham
      control, further supporting the rampant neurodegenerative pathology in TBI
      secondary cell death. These findings indicate that AD-like pathological features
      may prove to be valuable markers and therapeutic targets for late stage TBI. J.
      Cell. Physiol. 232: 665-677, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699792
TI  - Evidence-based occupational therapy for people with dementia and their families:
      What clinical practice guidelines tell us and implications for practice.
AB  - BACKGROUND/AIM: The first evidence-based Clinical Practice Guidelines and
      Principles of Care for People with Dementia in Australia have been released. The
      Guidelines detail a number of important evidence-based recommendations for
      occupational therapists. The aim of this paper is (1) to provide an overview of
      Guideline development, and (2) to describe the evidence supporting a
      recommendation for occupational therapy. Common characteristics of effective
      occupational therapy programmes for people with dementia are described. METHODS:
      Guideline development involved adaptation of existing high-quality guidelines
      developed overseas and 17 systematic reviews to ensure that the most recent high
      quality evidence was included. One of the systematic reviews involved examining
      the evidence for interventions to promote independence in people with dementia.
      Specifically, we looked at the evidence for occupational therapy and its effect
      on activities of daily living, quality of life and carer impact. RESULTS: A total
      of 109 recommendations are included in the Guidelines. Occupational therapy was
      found to significantly increase independence in activities of daily living and
      improve quality of life. Effective occupational therapy programmes involve:
      environmental assessment, problem solving strategies, carer education and
      interactive carer skills training. CONCLUSION: Occupational therapists working
      with people with dementia in community settings should ensure that their time is
      spent on those aspects of intervention that are shown to be effective.

PMID- 27699795
TI  - Technology Optimization of Lysozyme's Fresh Maintaining Effect on Apple.
AB  - Lysozyme is a kind of alkaline globin, which functions well in the degradation of
      the cell wall of microbe. Currently, lysozyme is widely used in various fields,
      such as medicine, fruit, and vegetable industry, dairy industry, and so on.
      Therefore, the exploitation and utilization of lysozyme is of significant
      economic benefit. Taking apple as material, weight loss ratio and reducing sugar
      content as objectives, this paper studied the fresh-keeping effect of lysozyme.
      Influential factors, lysozyme concentration, soaking time, modified temperature,
      and reaction time were discussed in detail. The results showed that reducing
      sugar content was 2.043% and the weight loss ratio was the minimum in the
      presence of soaking time of 2 min, modified temperature of 65  degrees C,
      reaction time of 4 d, and lysozyme concentration of 0.5 g/L.

PMID- 27699796
TI  - Electrophysiological revelations of trial history effects in a color oddball
      search task.
AB  - In visual oddball search tasks, viewing a no-target scene (i.e., no-target
      selection trial) leads to the facilitation or delay of the search time for a
      target in a subsequent trial. Presumably, this selection failure leads to biasing
      attentional set and prioritizing stimulus features unseen in the no-target scene.
      We observed attention-related ERP components and tracked the course of
      attentional biasing as a function of trial history. Participants were instructed
      to identify color oddballs (i.e., targets) shown in varied trial sequences. The
      number of no-target scenes preceding a target scene was increased from zero to
      two to reinforce attentional biasing, and colors presented in two successive no
      target scenes were repeated or changed to systematically bias attention to
      specific colors. For the no-target scenes, the presentation of a second no-target
      scene resulted in an early selection of, and sustained attention to, the changed
      colors (mirrored in the frontal selection positivity, the anterior N2, and the
      P3b). For the target scenes, the N2pc indicated an earlier allocation of
      attention to the targets with unseen or remotely seen colors. Inhibitory control
      of attention, shown in the anterior N2, was greatest when the target scene was
      followed by repeated no-target scenes with repeated colors. Finally, search times
      and the P3b were influenced by both color previewing and its history. The current
      results demonstrate that attentional biasing can occur on a trial-by-trial basis
      and be influenced by both feature previewing and its history.

PMID- 27699794
TI  - Steady-state visual evoked potentials as a research tool in social affective
      neuroscience.
AB  - Like many other primates, humans place a high premium on social information
      transmission and processing. One important aspect of this information concerns
      the emotional state of other individuals, conveyed by distinct visual cues such
      as facial expressions, overt actions, or by cues extracted from the situational
      context. A rich body of theoretical and empirical work has demonstrated that
      these socioemotional cues are processed by the human visual system in a
      prioritized fashion, in the service of optimizing social behavior. Furthermore,
      socioemotional perception is highly dependent on situational contexts and
      previous experience. Here, we review current issues in this area of research and
      discuss the utility of the steady-state visual evoked potential (ssVEP) technique
      for addressing key empirical questions. Methodological advantages and caveats are
      discussed with particular regard to quantifying time-varying competition among
      multiple perceptual objects, trial-by-trial analysis of visual cortical
      activation, functional connectivity, and the control of low-level stimulus
      features. Studies on facial expression and emotional scene processing are
      summarized, with an emphasis on viewing faces and other social cues in emotional
      contexts, or when competing with each other. Further, because the ssVEP technique
      can be readily accommodated to studying the viewing of complex scenes with
      multiple elements, it enables researchers to advance theoretical models of
      socioemotional perception, based on complex, quasinaturalistic viewing
      situations.

PMID- 27699793
TI  - Genetic architecture of plant stress resistance: multi-trait genome-wide
      association mapping.
AB  - Plants are exposed to combinations of various biotic and abiotic stresses, but
      stress responses are usually investigated for single stresses only. Here, we
      investigated the genetic architecture underlying plant responses to 11 single
      stresses and several of their combinations by phenotyping 350 Arabidopsis
      thaliana accessions. A set of 214 000 single nucleotide polymorphisms (SNPs) was
      screened for marker-trait associations in genome-wide association (GWA) analyses
      using tailored multi-trait mixed models. Stress responses that share
      phytohormonal signaling pathways also share genetic architecture underlying these
      responses. After removing the effects of general robustness, for the 30 most
      significant SNPs, average quantitative trait locus (QTL) effect sizes were larger
      for dual stresses than for single stresses. Plants appear to deploy broad
      spectrum defensive mechanisms influencing multiple traits in response to combined
      stresses. Association analyses identified QTLs with contrasting and with similar
      responses to biotic vs abiotic stresses, and below-ground vs above-ground
      stresses. Our approach allowed for an unprecedented comprehensive genetic
      analysis of how plants deal with a wide spectrum of stress conditions.

PMID- 27699797
TI  - Intermuscular coherence in amyotrophic lateral sclerosis: A preliminary
      assessment.
AB  - INTRODUCTION: Simple laboratory tests of upper motor neuron involvement in
      amyotrophic lateral sclerosis (ALS) are not available. Intermuscular coherence
      has been shown to distinguish patients with primary lateral sclerosis, a pure
      upper motor neuron disorder, from normal subjects, suggesting it could be useful
      for assessing ALS. We aimed to determine whether intermuscular coherence can
      distinguish ALS patients from normal subjects. METHODS: We measured biceps
      brachii and brachioradialis activity using surface electromyography while
      subjects held the elbow at flexion and the forearm in semipronation.
      Intermuscular coherence was calculated at between 20 and 40 Hz in 15 ALS patients
      and 15 normal subjects. RESULTS: On average, intermuscular coherence was 3.8-fold
      greater in normal subjects than in ALS patients (P < 0.01), and it distinguished
      ALS patients from normal subjects with a sensitivity of 87% and specificity of
      87%. CONCLUSION: Intermuscular coherence measurement is a rapid, painless method
      that may detect upper motor neuron dysfunction in ALS. Muscle Nerve 55: 862-868,
      2017.

PMID- 27699798
TI  - Reply.

PMID- 27699799
TI  - Comment on stereotactic body radiation therapy for small primary or recurrent
      hepatocellular carcinoma-Authors' reply.

PMID- 27699800
TI  - Evaluation of a preliminary method to examine antecedent and consequent
      contributions to noncompliance.
AB  - We evaluated a preliminary method for examining the antecedent and consequent
      contributions to noncompliance exhibited by two children with disabilities. In
      Phase 1, we assessed whether noncompliance was a result of a skill deficit. For
      one participant, we then conducted a functional analysis to determine the
      variables maintaining noncompliance in Phase 2. In Phase 3, we conducted a
      treatment evaluation to increase compliance for each participant. We identified
      the antecedent and consequent variables responsible for noncompliance and
      developed an effective intervention for both participants.

PMID- 27699801
TI  - Self-Other Differences in Student Drinking Norms Research: The Role of Impression
      Management, Self-Deception, and Measurement Methodology.
AB  - BACKGROUND: Data-driven student drinking norms interventions are based on
      reported normative overestimation of the extent and approval of an average
      student's drinking. Self-reported differences between personal and perceived
      normative drinking behaviors and attitudes are taken at face value as evidence of
      actual levels of overestimation. This study investigates whether commonly used
      data collection methods and socially desirable responding (SDR) may inadvertently
      impede establishing "objective" drinking norms. METHODS: U.K. students (N = 421;
      69% female; mean age 20.22 years [SD = 2.5]) were randomly assigned to 1 of 3
      versions of a drinking norms questionnaire: The standard multi-target
      questionnaire assessed respondents' drinking attitudes and behaviors (frequency
      of consumption, heavy drinking, units on a typical occasion) as well as drinking
      attitudes and behaviors for an "average student." Two deconstructed versions of
      this questionnaire assessed identical behaviors and attitudes for participants
      themselves or an "average student." The Balanced Inventory of Desirable
      Responding was also administered. RESULTS: Students who answered questions about
      themselves and peers reported more extreme perceived drinking attitudes for the
      average student compared with those reporting solely on the "average student."
      Personal and perceived reports of drinking behaviors did not differ between
      multitarget and single-target versions of the questionnaire. Among those who
      completed the multitarget questionnaire, after controlling for demographics and
      weekly drinking, SDR was related positively with the magnitude of difference
      between students' own reported behaviors/attitudes and those perceived for the
      average student. CONCLUSIONS: Standard methodological practices and socially
      desirable responding may be sources of bias in peer norm overestimation research.

PMID- 27699802
TI  - Uromodulin gene variants and their association with renal function and blood
      pressure in cats: a pilot study.
AB  - OBJECTIVES: In humans, genome-wide association studies have identified variants
      in the uromodulin gene (UMOD) associated with blood pressure and renal function.
      This study aimed to evaluate the association of single nucleotide polymorphisms
      at the UMOD locus with renal function and blood pressure in cats. METHODS: We
      retrospectively identified cats aged 14 years that had participated in a
      geriatric monitoring program, and from which stored DNA samples were available,
      from a computerised database. We then measured the association of specific single
      nucleotide polymorphisms in the feline UMOD gene with renal function and systolic
      blood pressure as continuous variables and, also, the dichotomous outcome of
      azotaemic chronic kidney disease and systemic hypertension. RESULTS: Eight
      intronic single nucleotide polymorphisms, one 1372 base pairs upstream from UMOD
      and two exonic single nucleotide polymorphisms were evaluated in 227 cats with
      renal and blood pressure data. An analysis of 188 cats found four single
      nucleotide polymorphisms to be significantly associated (P<0.01) with systolic
      blood pressure although all were in linkage disequilibrium. No significant
      associations were identified between single nucleotide polymorphisms and renal
      function or chronic kidney disease. CLINICAL SIGNIFICANCE: Results of this pilot
      study suggest that genetic variation in UMOD might influence blood pressure in
      cats, similar to findings in humans. Validation of these results is required.

PMID- 27699803
TI  - Quorum Sensing Involved in the Spoilage Process of the Skin and Flesh of Vacuum
      Packaged Farmed Turbot (Scophthalmus maximus) Stored at 4  degrees C.
AB  - Fish skin has both positive and negative effects on the shelf-life of the fish.
      This study aimed to investigate the spoilage process of the skin and flesh of
      refrigerated farmed turbot (Scophthalmus maximus) with vacuum packaging.
      Microbial community changes were analyzed by combining culture-dependent and
      culture-independent methods. The results indicated that the shelf-life of vacuum
      packaged refrigerated turbot was 16 d; skin mucus was the interference factor of
      turbot quality. The culture-dependent analysis demonstrated that the total viable
      counts and the population of H2 S-producing bacteria, Pseudomonas spp.,
      Enterobacteriaceae spp., and lactic acid bacteria in skin had a range of 0.45 to
      1.40 log (CFU/g) higher than the microbial numbers in flesh after 16 d in
      storage. 16S high throughout sequencing results demonstrated that the
      compositions of spoilage microbes were similar in skin and flesh. Shewanella
      spp., followed by Carnobacterium spp., was the dominant spoilage organism at day
      16. Quorum sensing (QS) signaling activity increased during the storage.
      Exogenous N-butanoyl-L-homoserinelactone(C4-HSL) and N-hexanoyl-Lhomoserine
      lactone (C6-HSL) significantly accelerated the spoilage process of refrigerated
      turbot, while the addition of 4, 5-Dihydroxypentane-2, 3-dione (DPD) prolonged
      the lag phase duration. Therefore, QS may be involved in the spoilage process of
      refrigerated turbot.

PMID- 27699804
TI  - Direct detection of mecA, blaSHV , blaCTX-M , blaTEM and blaOXA genes from
      positive blood culture bottles by multiplex-touchdown PCR assay.
AB  - : Methicillin-resistant staphylococci (MRS) and ESBL(Extended-Spectrum beta
      Lactamase)-producing bacteria are the most important resistant pathogens in
      sepsis. In this study, a new multiplex-touchdown PCR method (MT-PCR) was
      developed to detect rapidly and simultaneously the presence of mecA, blaSHV ,
      blaCTX-M , blaTEM and blaOXA genes from positive blood culture bottles. The
      technique showed a sensitivity of 103  CFU ml-1 for mecA detection and of 102 
      CFU ml-1 for other genes, and 100% specificity in the detection of all genes. All
      genes were detected in the spiked blood culture bottles artificially contaminated
      with reference strains. Three methicillin-resistant S. aureus (MRSA), two
      methicillin-resistant S. epidermidis (MRSE) and 32 ESBL-producing bacteria, were
      isolated from the clinical blood culture specimens in 48 h by standard
      microbiological procedures. The corresponding genes were detected directly in the
      three MRSA, two MRSE and 29 ESBL-producing bacteria from the clinical blood
      culture specimens in 4 h by MT-PCR assay. None of the blaSHV , blaCTX-M , blaTEM
      and blaOXA genes were detected in three other bottles with ESBL-producing
      bacteria because of other ESBL genotypes in the pathogens. Likewise, all bottles
      proven negative by culture remained negative by PCR. The proposed method was
      rapid, sensitive and specific, and was able to directly detect the genes of MRS
      and ESBL-producing bacteria from the blood culture bottles. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Many studies on the development of PCR for the detection of
      resistance genes have already been published, including multiplex PCR methods.
      However, cross-amplification reactions can be a major concern in multiplex PCR
      methods. In this study, we developed a highly sensitive and specific multiplex
      touchdown PCR assay for simultaneous detection of mecA, blaSHV , blaCTX-M ,
      blaTEM and blaOXA genes from positive blood culture bottles, cross-amplification
      was absent and false-positive results were not obtained.

PMID- 27699805
TI  - A protein extraction method for low protein concentration solutions compatible
      with the proteomic analysis of rubber particles.
AB  - The extraction of high-purity proteins from the washing solution (WS) of rubber
      particles (also termed latex-producing organelles) from laticifer cells in rubber
      tree for proteomic analysis is challenging due to the low concentration of
      proteins in the WS. Recent studies have revealed that proteins in the WS might
      play crucial roles in natural rubber biosynthesis. To further examine the
      involvement of these proteins in natural rubber biosynthesis, we designed an
      efficiency method to extract high-purity WS proteins. We improved our current
      borax and phenol-based method by adding reextraction steps with phenol (REP) to
      improve the yield from low protein concentration samples. With this new method,
      we extracted WS proteins that were suitable for proteomics. Indeed, compared to
      the original borax and phenol-based method, the REP method improved both the
      quality and quantity of isolated proteins. By repeatedly extracting from low
      protein concentration solutions using the same small amount of phenol, the REP
      method yielded enough protein of sufficiently high-quality from starting samples
      containing less than 0.02 mg of proteins per milliliter. This method was
      successfully applied to extract the rubber particle proteins from the WS of
      natural rubber latex samples. The REP-extracted WS proteins were resolved by 2DE,
      and 28 proteins were positively identified by MS. This method has the potential
      to become widely used for the extraction of proteins from low protein
      concentration solutions for proteomic analysis.

PMID- 27699806
TI  - Germline stem cells are critical for sexual fate decision of germ cells.
AB  - Egg or sperm? The mechanism of sexual fate decision in germ cells has been a long
      standing issue in biology. A recent analysis identified foxl3 as a gene that
      determines the sexual fate decision of germ cells in the teleost fish, medaka.
      foxl3/Foxl3 acts in female germline stem cells to repress commitment into male
      fate (spermatogenesis), indicating that the presence of mitotic germ cells in the
      female is critical for continuous sexual fate decision of germ cells in medaka
      gonads. Interestingly, foxl3 is found in most vertebrate genomes except for
      mammals. This provides the interesting possibility that the sexual fate of germ
      cells in mammals is determined in a different way compared to foxl3-possessing
      vertebrates. Considering the fact that germline stem cells are the cells where
      foxl3 begins to express and sexual fate decision initiates and mammalian ovary
      does not have typical germline stem cells, the mechanism in mammals may have been
      co-evolved with germline stem cell loss in mammalian ovary.

PMID- 27699807
TI  - Diversity and linkage disequilibrium in farmed Tasmanian Atlantic salmon.
AB  - Farmed Atlantic salmon (Salmo salar) is a globally important production species,
      including in Australia where breeding and selection has been in progress since
      the 1960s. The recent development of SNP genotyping platforms means genome-wide
      association and genomic prediction can now be implemented to speed genetic gain.
      As a precursor, this study collected genotypes at 218 132 SNPs in 777 fish from a
      Tasmanian breeding population to assess levels of genetic diversity, the strength
      of linkage disequilibrium (LD) and imputation accuracy. Genetic diversity in
      Tasmanian Atlantic salmon was lower than observed within European populations
      when compared using four diversity metrics. The distribution of allele
      frequencies also showed a clear difference, with the Tasmanian animals carrying
      an excess of low minor allele frequency variants. The strength of observed LD was
      high at short distances (<25 kb) and remained above background for marker pairs
      separated by large chromosomal distances (hundreds of kb), in sharp contrast to
      the European Atlantic salmon tested. Genotypes were used to evaluate the accuracy
      of imputation from low density (0.5 to 5 K) up to increased density SNP sets (78
      K). This revealed high imputation accuracies (0.89-0.97), suggesting that the use
      of low density SNP sets will be a successful approach for genomic prediction in
      this population. The long-range LD, comparatively low genetic diversity and high
      imputation accuracy in Tasmanian salmon is consistent with known aspects of their
      population history, which involved a small founding population and an absence of
      subsequent introgression. The findings of this study represent an important first
      step towards the design of methods to apply genomics in this economically
      important population.

PMID- 27699808
TI  - A review of mortality associated with elongate mineral particle (EMP) exposure in
      occupational epidemiology studies of gold, talc, and taconite mining.
AB  - BACKGROUND: Mining of gold, taconite, and talc may involve exposure to elongate
      mineral particles (EMP). The involved EMPs are typically non-asbestiform, include
      dimensions that regulatory definitions exclude, and have been less studied.
      METHODS: A review of the literature was undertaken for this exposure and
      occupational epidemiological studies that occur in gold, talc, and taconite
      mining. RESULTS: Quantitative EMP exposure information in these industries is
      incomplete. However, there are consistent findings of pneumoconiosis in each of
      these types of mining. A recent case-control study suggests a possible
      association between this exposure and mesothelioma. Lung cancer is inconsistently
      reported in these industries and is an unlikely outcome of non-asbestiform EMP
      exposure. There is evidence of cardiovascular mortality excess across all of
      these types of mining. CONCLUSIONS: Non-malignant respiratory disease and
      cardiovascular mortality have been consistently increased in these industries.
      Further investigation, including additional insights for the role of non
      asbestiform EMP, is warranted. Am. J. Ind. Med. 59:1047-1060, 2016. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27699809
TI  - Complexes of a Zn-metalloenzyme binding site with hydroxamate-containing ligands.
      A case for detailed benchmarkings of polarizable molecular mechanics/dynamics
      potentials when the experimental binding structure is unknown.
AB  - Zn-metalloproteins are a major class of targets for drug design. They constitute
      a demanding testing ground for polarizable molecular mechanics/dynamics aimed at
      extending the realm of quantum chemistry (QC) to very long-duration molecular
      dynamics (MD). The reliability of such procedures needs to be demonstrated upon
      comparing the relative stabilities of competing candidate complexes of inhibitors
      with the recognition site stabilized in the course of MD. This could be necessary
      when no information is available regarding the experimental structure of the
      inhibitor-protein complex. Thus, this study bears on the phosphomannose isomerase
      (PMI) enzyme, considered as a potential therapeutic target for the treatment of
      several bacterial and parasitic diseases. We consider its complexes with 5
      phospho-d-arabinonohydroxamate and three analog ligands differing by the number
      and location of their hydroxyl groups. We evaluate the energy accuracy expectable
      from a polarizable molecular mechanics procedure, SIBFA. This is done by
      comparisons with ab initio quantum-chemistry (QC) calculations in the following
      cases: (a) the complexes of the four ligands in three distinct structures
      extracted from the entire PMI-ligand energy-minimized structures, and totaling up
      to 264 atoms; (b) the solvation energies of several energy-minimized complexes of
      each ligand with a shell of 64 water molecules; (c) the conformational energy
      differences of each ligand in different conformations characterized in the course
      of energy-minimizations; and (d) the continuum solvation energies of the ligands
      in different conformations. The agreements with the QC results appear convincing.
      On these bases, we discuss the prospects of applying the procedure to ligand
      macromolecule recognition problems. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699810
TI  - Potential of 13 linked autosomal short tandem repeat loci in pairwise kinship
      analysis.
AB  - In this study, a panel of 13 STR loci locate on chromosome 3, 4, and 17 (D3S2402,
      D3S2452, D3S1766, D3S4554, D3S2388, D3S3051, D3S3053, D4S2404, D4S2364,
      AC001348A, AC001348B, D17S975, and D17S1294) were assessed for pairwise kinship
      analysis. Map distances between these STR loci ranged from 0.07 cM to 97.03 cM.
      The population genetic study of Chinese Han population showed that linkage
      disequilibrium exists in two clusters of closely linked markers (D4S2404-D4S2364
      and D17S975-D17S1294), in which the recombination fractions were 0.0026 and
      0.0001, respectively. The recombination fractions derived from the Rutgers Map
      for the closely linked markers (genetic distance < 0.5 cM) were significant
      underestimates in comparison to those of direct observation of STR transmissions
      in families. When effect of linkage on pairwise kinship testing was evaluated by
      comparing likelihood ratio (LR) values taking linkage into account, overall LR
      values increased. But extremely low LRs were also observed. Finally, the power of
      the 13 STR loci to discriminate relationship among full-sibs, half-sibs,
      grandparent-grandchild, uncle-niece, and unrelated pairs was assessed with a
      category fraction. The results showed that about 72.64% of full-sib pairs and
      about 82.84% of unrelated pairs could be classified correctly. But the category
      fractions of second-degree relationships drastically reduced to 7.34-35.48%. If
      only pairs of grandparent-grandchild, half-sibs, and uncle-niece were
      distinguished, the category fraction was 0.5512, 0.1147, and 0.4362,
      respectively. Our study results demonstrated that linked STRs were helpful to
      differentiate the most frequent relationships in pairwise kinship analysis.

PMID- 27699811
TI  - Task distribution, work environment, and perceived health discomforts among
      Indian ceramic workers.
AB  - BACKGROUND: The study examined the work environment of Indian ceramics workers
      and assessed associations between work hazards, work category, and self-reported
      symptoms. METHODS: The multi-method ergonomic review technique (MMERT)
      checkpoints was used for work analysis and prevalence of self-reported symptoms
      among 329 male workers. RESULTS: Ambient temperature and relative humidity in
      ceramic industries were 39.9 degrees C and 17.4% respectively. Musculoskeletal
      discomfort was observed as a primary complaint; especially lower extremity pain
      (45%). Load handlers and machine operators had the highest levels of work
      hazards, including high skill requirement, strenuous work posture, poor
      commitment by the organization. Poor job autonomy, task clarity, hot workplace,
      inappropriate workplace design, inadequate auxiliary support, and mental overload
      were significantly associated with self-reported symptoms (P < 0.001).
      CONCLUSION: Work categories are associated with work hazards and may lead to
      various health symptoms among ceramic workers. Control of workplace hazards may
      lower rates of symptoms and thus may lead to improved health, productivity, and
      well-being. Am. J. Ind. Med. 59:1145-1155, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699812
TI  - Lactate release from astrocytes to neurons contributes to cocaine memory
      formation.
AB  - The identification of neural substrates underlying the long lasting debilitating
      impact of drug cues is critical for developing novel therapeutic tools. Metabolic
      coupling has long been considered a key mechanism through which astrocytes and
      neurons actively interact in response of neuronal activity, but recent findings
      suggested that disrupting metabolic coupling may represent an innovative approach
      to prevent memory formation, in particular drug-related memories. Here, we review
      converging evidence illustrating how memory and addiction share neural circuitry
      and molecular mechanisms implicating lactate-mediated metabolic coupling between
      astrocytes and neurons. With several aspects of addiction depending on mnemonic
      processes elicited by drug experience, disrupting lactate transport involved in
      the formation of a pathological learning, linking the incentive, and motivational
      effects of drugs with drug-conditioned stimuli represent a promising approach to
      encourage abstinence.

PMID- 27699813
TI  - FOXO3a Expression Regulated by ERK Signaling is Inversely Correlated With Y-Box
      Binding Protein-1 Expression in Prostate Cancer.
AB  - BACKGROUND: FOXO3a is a member of the forkhead O transcription factors. FOXO3a
      induces the factors that contribute to cell cycle arrest and is considered a
      tumor suppressor in several malignant tumors. Y-box binding protein-1 (YB-1) is a
      multifunctional protein whose high expression is correlated with poor prognoses
      in various malignant tumors. In the current study, we investigated the
      relationship between FOXO3a and YB-1 to validate their functional roles in
      prostate cancer. METHODS: Western blotting and cytotoxicity assays were conducted
      in prostate cancer cells, LNCaP, and 22Rv1 cells. We also evaluated the protein
      expressions of FOXO3a and YB-1 in human prostate cancer tissues, using radical
      prostatectomy specimens. Then, we investigated the correlations between protein
      expressions and clinicopathologic parameters. RESULTS: We found that both FOXO3a
      and YB-1 proteins were phosphorylated by ERK signaling, resulting in FOXO3a
      inactivation and YB-1 activation in LNCaP and 22Rv1 cells. Inversely, inhibition
      of MEK or treatment with metformin activated FOXO3a through inactivation of ERK
      signaling and suppressed the viability of LNCaP and 22Rv1 cells in a dose
      dependent manner. In immunohistochemical analysis, FOXO3a nuclear expression was
      inversely correlated with YB-1 nuclear expression (P < 0.0001). Furthermore, high
      FOXO3a nuclear expression was inversely correlated with a higher Gleason grade (P
      < 0.0001) and higher preoperative PSA (P = 0.0437). CONCLUSIONS: These results
      showed that in prostate cancer, FOXO3a, and YB-1 play inverse reciprocal roles as
      a tumor-suppressor gene and oncogene, respectively, through their master
      regulator ERK. Prostate 77:145-153, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699814
TI  - Impact of white-tailed deer on the spread of Borrelia burgdorferi.
AB  - There is a public perception that the white-tailed deer Odocoileus virginianus
      (Artiodactyla: Cervidae) is the main reservoir supporting the maintenance and
      spread of the causative agent of Lyme disease, Borrelia burgdorferi. This study
      examines the pathogen prevalence rate of Borrelia in adult Ixodes scapularis
      (Ixodida: Ixodidae), the black-legged tick, collected from white-tailed deer and
      compares it with pathogen prevalence rates in adult ticks gathered by dragging
      vegetation in two contiguous counties west of the Hudson Valley in upstate New
      York. In both Broome and Chenango Counties, attached and unattached ticks
      harvested from white-tailed deer had significantly lower prevalences of B.
      burgdorferi than those collected from vegetation. No attached ticks on deer (n =
      148) in either county, and only 2.4 and 7.3% of unattached ticks (n = 389) in
      Broome and Chenango Counties, respectively, were harbouring the pathogen. This
      contrasts with the finding that 40.8% of ticks in Broome County and 46.8% of
      ticks in Chenango County collected from vegetation harboured the pathogen. These
      data suggest that a mechanism in white-tailed deer may aid in clearing the
      pathogen from attached deer ticks, although white-tailed deer do contribute to
      the spatial distribution of deer tick populations and also serve as deadend host
      breeding sites for ticks.

PMID- 27699815
TI  - Impact of the implementation of vasoactive drug protocols on safety and efficacy
      in the treatment of critically ill patients.
AB  - WHAT IS KNOWN AND OBJECTIVE: The correct management of high-alert medications is
      a priority issue in expert recommendations for improving the clinical safety of
      patients. Objectives were to assess the impact of the implementation of
      vasoactive drug (VAD) protocols on safety and efficacy in the treatment of
      critically ill patients. METHODS: A prospective before-and-after study on the
      implementation of different VAD protocols, comparing medication errors (MEs)
      rates, mean intensive care unit (ICU) stay, mean blood pressure (MAP), heart rate
      (HR) and oxygen saturation. RESULTS AND DISCUSSION: The study included 432
      patients. There was a statistically significant decrease in prescribing errors
      (55.9%), validation errors (68.1%) and medication administration records (MAR)
      errors (78.8%). No differences were found between the two phases in ICU stay,
      MAP, HR and oxygen saturation. WHAT IS NEW AND CONCLUSION: Implementation of
      protocols decreases variability in clinical practice, reduces the incidence of
      MEs and maintains the effectiveness of VAD therapy in critically ill patients.

PMID- 27699816
TI  - Disparities in precarious workers' health care access in South Korea.
AB  - BACKGROUND: This study explored whether precarious workers have difficulties in
      health care access as compared with non-precarious workers. METHODS: The 2008
      Korean Community Health Survey data were used for this study. Information was
      obtained on 51,322 participants (40,514 non-precarious workers and 10,808
      precarious workers). Precarious workers were defined as part-time or contingent
      workers. RESULTS: Precarious workers had significantly higher risk of limited
      access to hospitals (OR = 1.14; 95% CI: 1.06-1.22) and dentists (OR = 1.28; 95%
      CI: 1.21-1.36) than non-precarious workers; disparities in doctor contacts among
      precarious workers were mostly linked to not having enough money. The risk of not
      receiving preventive care-medical checkups (OR = 0.52; 95% CI: 0.49-0.55) or
      cancer screenings (OR = 0.82; 95% CI: 0.77-0.86)-was also significantly elevated
      among precarious workers. CONCLUSION: We found that precarious workers had more
      difficulty accessing health care or receiving health checkups or cancer
      screenings than their non-precarious counterparts. Am. J. Ind. Med. 59:1136-1144,
      2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699818
TI  - Discrimination slope and integrated discrimination improvement - properties,
      relationships and impact of calibration.
AB  - Discrimination slope, defined as the slope of a linear regression of predicted
      probabilities of event derived from a prognostic model on the binary event
      status, has recently gained popularity as a measure of model performance. It is
      as a building block for the integrated discrimination improvement that equals the
      difference in discrimination slopes between the two models being compared.
      Several authors have pointed out that it does not make sense to apply the
      integrated discrimination improvement and discrimination slope when working with
      mis-calibrated models, whereas others have raised concerns about the ability of
      improving discrimination slope without adding new information. In this paper, we
      show that under certain assumptions the discrimination slope is asymptotically
      related to two other R-squared measures, one of which is a rescaled version of
      the Brier score, known to be proper. Furthermore, we illustrate how a simple
      recalibration makes the slope equal to the rescaled Brier R-squared metric. We
      also show that the discrimination slope can be interpreted as a measure of
      reduction in expected regret for the Gini-Brier regret function. Using
      theoretical and practical examples, we illustrate how all of these metrics are
      affected by different levels of model mis-calibration. In particular, we
      demonstrate that simple recalibration ascertaining calibration in-the-large and
      calibration slope equal to 1 are not sufficient to correct for some forms of mis
      calibration. We conclude that R-squared metrics, including the discrimination
      slope, offer an attractive choice for quantifying model performance as long as
      one accounts for their sensitivity to model calibration. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27699817
TI  - Revisiting cancer 15 years later: Exploring mortality among agricultural and non
      agricultural workers in the Serrana Region of Rio de Janeiro.
AB  - : Background Agricultural production has expanded dramatically throughout Brazil.
      Previous research in the Serrana Region found that from 1979 to 1998,
      agricultural workers experienced high mortality rates from certain cancers
      compared to non-agricultural workers [Meyer et al. (2003): Environ Res 93:264
      271]. METHODS: New data were obtained for 1999-2013 and Mortality Odds Ratios
      (MORs) were utilized to compare cancer and other mortality between male
      agricultural workers in the Serrana Region and non-agricultural workers in the
      Serrana Region, Rio de Janeiro, and Porto Alegre, and to compare mortality odds
      to previous decades. RESULTS: Respectively, compared to aforementioned reference
      groups, agricultural workers experienced highest MORs for stomach (1.55 [95%CI:
      1.13-2.12], 2.30 [95%CI: 1.72-3.08], 2.28 [95%CI: 1.69-3.08]) and esophageal
      cancers (95%CI: 1.93 [1.38-2.7], 1.93 [95%CI: 1.38-2.71], 3.12 [95%CI: 2.30
      4.24]), greater than reported in previous decades. Agricultural workers
      experienced higher mortality for external-causes, respiratory, and cardiovascular
      problems compared to urban reference-groups. CONCLUSION: Agricultural workers may
      be at increasing risk for cancer and other mortality. Efforts are needed to
      investigate distinct risk-factors among this group. Am. J. Ind. Med. 60:77-86,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699820
TI  - The structure and process of workers' compensation systems and the role of
      doctors: A comparison of Ontario and Quebec.
AB  - BACKGROUND: This study sought to identify impacts of compensation system
      characteristics on doctors in Quebec and Ontario. METHODS: (i) Legal analysis;
      (ii) Qualitative methods applied to documentation and individual and group
      interviews with doctors (34) and other system participants (31); and (iii) Inter
      jurisdictional transdisciplinary analysis involving cross-disciplinary
      comparative and integrative analysis of policy contexts, qualitative data, and
      the relationship between the two. RESULTS: In both jurisdictions the compensation
      board controlled decisions on work-relatedness and doctors perceived the
      bureaucratic process negatively. Gatekeeping roles differed between jurisdictions
      both in initial adjudication and in dispute processes. Quebec legislation gives
      greater weight to the opinion of the treating physician. These differences
      affected doctors' experiences. CONCLUSIONS: Policy-makers should contextualize
      the sources of the "evidence" they rely on from intervention research because
      findings may reflect a system rather than an intervention effect. Researchers
      should consider policy contexts to both adequately design a study and interpret
      their results. Am. J. Ind. Med. 59:1070-1086, 2016. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27699819
TI  - Prostate Specific Antigen-Growth Curve Model to Predict High-Risk Prostate
      Cancer.
AB  - PURPOSE: To investigate if a prostate specific antigen (PSA)-derived growth curve
      can predict the occurrence of high-risk prostate cancer (PrCA). METHODS: Data
      from 38,340 men randomized to the PrCA screening arm in the prostate, lung,
      colorectal, and ovarian cancer screening trial (PLCO) were used to develop a PSA
      growth curve model to estimate PSA rate of change. The model was then used to
      predict high-risk PrCA in clinical data available from 680,390 veterans seeking
      routine care. The PSA growth curve was modeled using non-linear mixed regression
      and the PSA rate was estimated by taking the 1st derivative of the growth curve
      equation at 1 year prior to diagnosis/exit. RESULTS: In the PLCO, PrCA incidence
      was 8.1%; ~19% of whom had high-risk PrCA. Overall, a PSA rate threshold of 0.37
      ng/ml/year had the best combination of sensitivity (97.2%) and specificity
      (97.3%) for detecting high-risk PrCA. In the VA data; 7,347 men were diagnosed
      with PrCA; of these 4,315 (58.7%) were diagnosed with high-risk PrCA. The PLCO
      optimal threshold of 0.37 ng/ml/year produced sensitivity = 95.5% and specificity
      = 85.2%. An optimal threshold of 0.99 ng/ml/year in AA produced sensitivity =
      89.1% and specificity = 80.0%. PSA rate was a better predictor than the single
      last PSA value. CONCLUSIONS: PSA growth curves predicted high-risk PrCA in the
      PLCO data. Fitting the same algorithm in the VA data produced lower specificity.
      Although encouraging, this finding underlines the need for further research to
      prospectively test the algorithm, especially for African-American men, the
      population group at highest risk of aggressive PrCA. Prostate 77:173-184, 2017.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27699821
TI  - Dissecting the effects of antibiotics on horizontal gene transfer: Analysis
      suggests a critical role of selection dynamics.
AB  - Horizontal gene transfer (HGT) is a major mechanism responsible for the spread of
      antibiotic resistance. Conversely, it is often assumed that antibiotics promote
      HGT. Careful dissection of the literature, however, suggests a lack of conclusive
      evidence supporting this notion in general. This is largely due to the lack of
      well-defined quantitative experiments to address this question in an unambiguous
      manner. In this review, we discuss the extent to which HGT is responsible for the
      spread of antibiotic resistance and examine what is known about the effect of
      antibiotics on the HGT dynamics. We focus on conjugation, which is the dominant
      mode of HGT responsible for spreading antibiotic resistance on the global scale.
      Our analysis reveals a need to design experiments to quantify HGT in such a way
      to facilitate rigorous data interpretation. Such measurements are critical for
      developing novel strategies to combat resistance spread through HGT.

PMID- 27699823
TI  - Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With
      Different Susceptibility to Experimental Autoimmune Prostatitis.
AB  - BACKGROUND: Experimental autoimmune prostatitis (EAP) is an autoimmune
      inflammatory disease of the prostate characterized by peripheral prostate
      specific autoimmune responses associated with prostate inflammation. EAP is
      induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants
      and shares important clinical and immunological features with the human disease
      chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: EAP was
      induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus
      complete Freunds adjuvant. Tactile allodynia was assessed using Von Frey fibers
      as a measure of pelvic pain at baseline and at different time points after
      immunization. Using conventional histology, immunohistochemistry, FACS analysis,
      and protein arrays, an interstrain comparative study of prostate cell
      infiltration and inflammation was performed. RESULTS: Chronic pelvic pain
      development was similar between immunized NOD and C57BL/6 mice, although the
      severity of leukocyte infiltration was greater in the first case. Coversely,
      minimal prostate cell infiltration was observed in immunized BALB/c mice, who
      showed no pelvic pain development. Increased numbers of mast cells, mostly
      degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while
      lower total counts and resting were observed in BALB/c mice. Prostate tissue from
      NOD mice revealed markedly increased expression levels of inflammatory cytokines,
      chemokines, adhesion molecules, vascular endothelial growth factor, and
      metalloproteinases. Similar results, but to a lesser extent, were observed when
      analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of
      the above mediators was very low in prostate tissue from immunized BALB/c mice,
      showing significantly slight increments only for CXCL1 and IL4. CONCLUSIONS: Our
      results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice
      develop different degrees of chronic pelvic pain, type, and amount of prostate
      cell infiltration and secretion of inflammatory mediators. Our results
      corroborate and support the notion that mice with different genetic background
      have different susceptibility to EAP induction. Prostate 77:94-104, 2017. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27699822
TI  - Analysis of isoquinoline alkaloids using chitosan-assisted liquid-solid
      extraction followed by microemulsion liquid chromatography employing a sub-2
      micron particle stationary phase.
AB  - A simple, efficient, and green chitosan-assisted liquid-solid extraction method
      was developed for the sample preparation of isoquinoline derivative alkaloids
      followed by microemulsion LC. The optimized mobile phase consisted of 0.8% w/v of
      ethyl acetate, 1.0% w/v of SDS, 8.0% w/v of n-butanol, 0.1% v/v acetic acid, and
      10% v/v ACN. Compared to pharmacopoeia method and organic solvent extraction,
      this new approach avoided the use of volatile organic solvents, replacing them
      with relatively small amounts of chitosan. Under the optimum conditions, good
      linearity (r2 > 0.9980) for all calibration curves and low detection limits
      between 0.05 and 0.10 MUg/mL were achieved. The presented procedure was
      successfully applied to determine alkaloids in Rhizoma coptidis with satisfactory
      recoveries (81.3-106.4%).

PMID- 27699824
TI  - Modeling of formation and prevention of a pure water zone in capillary
      isoelectric focusing with narrow pH range carrier ampholytes.
AB  - This paper comprises a continuation of computer simulation studies dealing with
      carrier ampholyte based CIEF in presence of narrow pH gradients. With this
      technique, amphoteric sample components with pI values outside the pH gradient
      are migrating isotachophoretically toward the cathode or anode whereas components
      with pI values within the gradient become focused. In order to understand the
      processes occurring in presence of the electric field, the behavior of both
      carrier ampholytes and amphoteric sample components is investigated by computer
      modeling. Characteristics of two pH unit gradients with end components having pI
      values at or around 7.00 and conditions that lead to the formation of a water
      zone at neutrality were investigated. Data obtained reveal that a zone of water
      is formed in focusing with carrier ampholytes when the applied pH range does not
      cover the neutral region, ends at pH 7.00 or begins at pH 7.00. The presence of
      additional amphoteric components that cover the neutrality region prevent water
      zone formation under current flow. This situation is met in experiments with
      narrow pH gradients that end or begin around neutrality. Simulation data reveal
      that no water zone evolves when atmospheric carbon dioxide dissolved in the
      catholyte causes the migration of carbonic acid (in the form of carbonate and/or
      hydrogen carbonate ions) from the catholyte through the focusing structure. An
      electrolyte change in the electrode solution does not have an impact on the
      focusing part but does change the isotachophoretic pattern migrating behind the
      leading ion.

PMID- 27699825
TI  - Elevated C-Peptides, Abdominal Obesity, and Abnormal Adipokine Profile are
      Associated With Higher Gleason Scores in Prostate Cancer.
AB  - BACKGROUND: Prostate cancer development is associated with numerous lifestyle
      factors (i.e., physical activity, nutrition intake) and metabolic perturbations.
      These factors have been studied independently; here, we used an integrative
      approach to characterize these lifestyle and metabolic parameters in men
      undergoing diagnostic prostate biopsies. METHODS: We prospectively evaluated 51
      consecutive men for body composition, metabolic factors including glucose- and
      lipid-related measures, as well as lifestyle factors prior to prostate biopsy.
      Evaluations were performed in a blinded manner and were subsequently related to
      biopsy outcomes for: (i) presence or absence of cancer; and (ii) where cancer was
      present, Gleason score. RESULTS: Serum C-peptide concentrations were
      significantly greater in participants with Gleason scores >=4 + 3 (2.8 +/- 1.1
      ng/ml) compared to those with Gleason 3 + 3 (1.4 +/- 0.6 ng/ml) or Gleason 3 + 4
      (1.3 +/- 0.8 ng/ml, P = 0.002), suggesting greater insulin secretion despite lack
      of differences in fasting glucose concentrations. Central adiposity, measured by
      waist circumference, was significantly greater in participants with Gleason >=4 +
      3 (110.1 +/- 7.4 cm) compared to those with Gleason 3 + 4 (102.0 +/- 9.5 cm, P =
      0.028). Men with Gleason >=4 + 3 also had significantly greater leptin
      concentrations than those with lower Gleason scores (Gleason >=4 + 3: 15.6 +/-
      3.3 ng/ml vs. Gleason 3 + 4: 8.1 +/- 8.1 ng/ml, P < 0.05) and leptin:adiponectin
      ratio (Gleason >=4 + 3: 9.7 +/- 6.1 AU, Gleason 3 + 4: 2.9 +/- 3.2, Gleason 3 +
      3: 2.4 +/- 2.1 AU, P = 0.013). CONCLUSIONS: We profiled a cluster of obesity
      related metabolic perturbations (C-peptide, central adiposity, leptin, and
      leptin:adiponectin ratios) which may associate with more aggressive prostate
      cancer histology. Prostate 77:211-221, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699826
TI  - Synthesis, Molecular Mechanism and Pharmacokinetic Studies of New Epoxy Lignan
      Based Derivatives.
AB  - The oxidative demethylation procedure for a new epoxy lignan isolated from Piper
      nigrum was applied to the synthesis of 3'-methoxy-3",4"-(methylenedioxy)-2,5
      epoxylignan-4'-ol-6'-one. This compound inhibited the mRNA expression of the
      protein patched homolog (Ptch) in human pancreatic cancer cells (PANC1) and
      therefore might be valuable as a probe for tumor-related disease. The
      pharmacokinetic profile of 3'-methoxy-3",4"-(methylenedioxy)-2,5-epoxylignan-4'
      ol-6'-one was rapidly determined using ultra-fast liquid chromatography. The
      compound was rapidly absorbed in blood.

PMID- 27699827
TI  - Rotator cuff tear state modulates self-renewal and differentiation capacity of
      human skeletal muscle progenitor cells.
AB  - Full thickness rotator cuff tendon (RCT) tears have long-term effects on RC
      muscle atrophy and fatty infiltration, with lasting damage even after surgical
      tendon repair. Skeletal muscle progenitor cells (SMPs) are critical for muscle
      repair in response to injury, but the inability of RC muscles to recover from
      chronic RCT tear indicates possible deficits in repair mechanisms. Here we
      investigated if muscle injury state was a crucial factor during human SMP
      expansion and differentiation ex vivo. SMPs were isolated from muscles in
      patients with no, partial-thickness (PT), or full-thickness (FT) RCT tears.
      Despite using growth factors, physiological niche stiffness, and muscle-mimetic
      extracellular matrix (ECM) proteins, we found that SMPs isolated from human RC
      muscle with RCT tears proliferated slower but fused into myosin heavy chain (MHC)
      positive myotubes at higher rates than SMPs from untorn RCTs. Proteomic analysis
      of RC muscle tissue revealed shifts in muscle composition with pathology, as
      muscle from massive RCT tears had increased ECM deposition compared with no tear
      RC muscle. Together these data imply that the remodeled niche in a torn RCT
      primes SMPs not for expansion but for differentiation, thus limiting longer-term
      self-renewal necessary for regeneration after surgical repair. (c) 2016
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      35:1816-1823, 2017.

PMID- 27699829
TI  - Evaluating the zebrafish embryo toxicity test for pesticide hazard screening.
AB  - Given the numerous chemicals used in society, it is critical to develop tools for
      accurate and efficient evaluation of potential risks to human and ecological
      receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be
      highly predictive of standard, more resource-intensive, juvenile fish acute
      toxicity tests. However, there is also evidence that fish embryos are less
      sensitive than juvenile fish for certain types of chemicals, including
      neurotoxicants. The utility of fish embryos for pesticide hazard assessment was
      investigated by comparing published zebrafish embryo toxicity data from
      pesticides with median lethal concentration 50% (LC50) data for juveniles of 3
      commonly tested fish species: rainbow trout, bluegill sunfish, and sheepshead
      minnow. A poor, albeit significant, relationship (r2  = 0.28; p < 0.05) was found
      between zebrafish embryo and juvenile fish toxicity when pesticides were
      considered as a single group, but a much better relationship (r2  = 0.64; p <
      0.05) when pesticide mode of action was factored into an analysis of covariance.
      This discrepancy is partly explained by the large number of neurotoxic pesticides
      in the dataset, supporting previous findings that commonly used fish embryo
      toxicity test endpoints are particularly insensitive to neurotoxicants. These
      results indicate that it is still premature to replace juvenile fish toxicity
      tests with embryo-based tests such as the Organisation for Economic Co-operation
      and Development Fish Embryo Acute Toxicity Test for routine pesticide hazard
      assessment, although embryo testing could be used with other screening tools for
      testing prioritization. Environ Toxicol Chem 2017;36:1221-1226. (c) 2016 SETAC.

PMID- 27699831
TI  - Newly Described Autoinflammatory Diseases in Pediatric Dermatology.
AB  - Specific gene mutations leading to dysregulation of innate immune response
      produce the expanding spectrum of monogenic autoinflammatory diseases (AIDs).
      They are characterized by seemingly unprovoked, recurrent episodes of systemic
      inflammation in which a myriad of manifestations usually affect skin. Novel
      genetic technologies have led to the discovery of new AIDs and phenotypes that
      were not previously clinically described. Consequently the number of AIDs is
      continuously growing and their recognition and the disclosure of their
      pathophysiology will prompt early diagnosis and targeted treatment of affected
      patients. The objective of the present work is to review those newly described
      AIDs with prominent dermatologic manifestations that may constitute a major
      criterion for their diagnosis.

PMID- 27699828
TI  - High-Content Screening Identifies Src Family Kinases as Potential Regulators of
      AR-V7 Expression and Androgen-Independent Cell Growth.
AB  - BACKGROUND: AR-V7 is an androgen receptor (AR) splice variant that lacks the
      ligand-binding domain and is isolated from prostate cancer cell lines. Increased
      expression of AR-V7 is associated with the transition from hormone-sensitive
      prostate cancer to more advanced castration-resistant prostate cancer (CRPC). Due
      to the loss of the ligand-binding domain, AR-V7 is not responsive to traditional
      AR-targeted therapies, and the mechanisms that regulate AR-V7 are still
      incompletely understood. Therefore, we aimed to explore existing classes of small
      molecules that may regulate AR-V7 expression and intracellular localization and
      their potential therapeutic role in CRPC. METHODS: We used AR high-content
      analysis (AR-HCA) to characterize the effects of a focused library of well
      characterized clinical compounds on AR-V7 expression at the single-cell level in
      PC3 prostate cancer cells stably expressing green fluorescent protein (GFP)-AR-V7
      (GFP-AR-V7:PC3). In parallel, an orthogonal AR-HCA screen of a small interfering
      (si)RNA library targeting 635 protein kinases was performed in GFP-AR-V7:PC3. The
      effect of the Src-Abl inhibitor PD 180970 was further characterized using cell
      proliferation assays, quantitative PCR, and western blot analysis in multiple
      hormone-sensitive and CRPC cell lines. RESULTS: Compounds that tended to target
      Akt, Abl, and Src family kinases (SFKs) decreased overall AR-V7 expression,
      nuclear translocation, absolute nuclear level, and/or altered nuclear
      distribution. We identified 20 protein kinases that, when knocked down, either
      decreased nuclear GFP-AR-V7 levels or altered AR-V7 nuclear distribution, a set
      that included the SFKs Src and Fyn. The Src-Abl dual kinase inhibitor PD180970
      decreased expression of AR-V7 by greater than 46% and decreased ligand
      independent transcription of AR target genes in the 22RV1 human prostate
      carcinoma cell line. Further, PD180970 inhibited androgen-independent cell
      proliferation in endogenous-AR-V7-expressing prostate cancer cell lines and also
      overcame bicalutamide resistance observed in the 22RV1 cell line. CONCLUSIONS:
      SFKs, especially Src and Fyn, may be important upstream regulators of AR-V7
      expression and represent promising targets in a subset of CRPCs expressing high
      levels of AR-V7. Prostate 77:82-93, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699830
TI  - Acute sensitivity of a broad range of freshwater mussels to chemicals with
      different modes of toxic action.
AB  - Freshwater mussels, one of the most imperiled groups of animals in the world, are
      generally underrepresented in toxicity databases used for the development of
      ambient water quality criteria and other environmental guidance values. Acute 96
      h toxicity tests were conducted to evaluate the sensitivity of 5 species of
      juvenile mussels from 2 families and 4 tribes to 10 chemicals (ammonia, metals,
      major ions, and organic compounds) and to screen 10 additional chemicals (mainly
      organic compounds) with a commonly tested mussel species, fatmucket (Lampsilis
      siliquoidea). In the multi-species study, median effect concentrations (EC50s)
      among the 5 species differed by a factor of <=2 for chloride, potassium, sulfate,
      and zinc; a factor of <=5 for ammonia, chromium, copper, and nickel; and factors
      of 6 and 12 for metolachlor and alachlor, respectively, indicating that mussels
      representing different families or tribes had similar sensitivity to most of the
      tested chemicals, regardless of modes of action. There was a strong linear
      relationship between EC50s for fatmucket and the other 4 mussel species across
      the 10 chemicals (r2  = 0.97, slope close to 1.0), indicating that fatmucket was
      similar to other mussel species; thus, this commonly tested species can be a good
      surrogate for protecting other mussels in acute exposures. The sensitivity of
      juvenile fatmucket among different populations or cultured from larvae of wild
      adults and captive-cultured adults was also similar in acute exposures to copper
      or chloride, indicating captive-cultured adult mussels can reliably be used to
      reproduce juveniles for toxicity testing. In compiled databases for all
      freshwater species, 1 or more mussel species were among the 4 most sensitive
      species for alachlor, ammonia, chloride, potassium, sulfate, copper, nickel, and
      zinc; therefore, the development of water quality criteria and other
      environmental guidance values for these chemicals should reflect the sensitivity
      of mussels. In contrast, the EC50s of fatmucket tested in the single-species
      study were in the high percentiles (>75th) of species sensitivity distributions
      for 6 of 7 organic chemicals, indicating mussels might be relatively insensitive
      to organic chemicals in acute exposures. Environ Toxicol Chem 2017;36:786-796.
      Published 2016 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- 27699832
TI  - Value of delayed gadolinium-enhanced magnetic resonance imaging of cartilage for
      the pre-operative assessment of cervical intervertebral discs.
AB  - The study was performed to preoperatively assess the cartilage integrity of
      cervical intervertebral discs (IVDs) using Delayed Gadolinium-Enhanced Magnetic
      Resonance Imaging of Cartilage (dGEMRIC). Therefore, 53 cervical intervertebral
      discs of nine preoperative patients with neck and shoulder/arm pain scheduled for
      discectomy (five females, four males; mean age: 47.1 +/- 8.4 years; range: 36-58
      years) were included for biochemical analysis in this retrospective study. The
      patients underwent 3T magnetic resonance imaging (MRI) including biochemical
      imaging with dGEMRIC and morphological, sagittal T2 weighted (T2w) imaging.
      Cervical IVDs were rated using an MRI based grading system for cervical IVDs on
      T2w images. Region-of-interest measurements were performed in the nucleus
      pulposus (NP) and annulus fibrosus (AF) and a dGEMRIC index was calculated. Our
      results demonstrated that IVDs scheduled for discectomy showed significantly
      lower dGEMRIC index compared to IVDs that did not require surgical intervention
      in NP and AF (NP: 898.4 +/- 191.9 ms vs. 1,150.3 +/- 320.7 ms, p = 0.008; AF:
      738.7 +/- 183.8 ms vs. 984.6 +/- 178.9 ms, p = 0.008). For Miyazaki score 3, the
      dGEMRIC indices were significantly lower in IVDs scheduled for surgery compared
      to non-operated discs for NP (p = 0.043) and AF (p = 0.018). In conclusion we
      could demonstrate that biochemical imaging with dGEMRIC is feasible in cervical
      IVDs. Significantly lower dGEMRIC index suggested GAG depletion in degenerated
      cervical IVD, scheduled for discectomy. (c) 2016 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 35:1824-1830, 2017.

PMID- 27699834
TI  - Editor's Annual Report: 2015-2016.

PMID- 27699833
TI  - Effects of cell type and configuration on anabolic and catabolic activity in 3D
      co-culture of mesenchymal stem cells and nucleus pulposus cells.
AB  - Tissue engineering constructs to treat intervertebral disc degeneration must
      adapt to the hypoxic and inflammatory degenerative disc microenvironment. The
      objective of this study was to determine the effects of two key design factors,
      cell type and cell configuration, on the regenerative potential of nucleus
      pulposus cell (NPC) and mesenchymal stem cell (MSC) constructs. Anabolic and
      catabolic activity was quantified in constructs of varying cell type (NPCs, MSCs,
      and a 50:50 co-culture) and varying configuration (individual cells and
      micropellets). Anabolic and catabolic outcomes were both dependent on cell type.
      Gene expression of Agg and Col2A1, glycosaminoglycan (GAG) content, and aggrecan
      immunohistochemistry (IHC), were significantly higher in NPC-only and co-culture
      groups than in MSC-only groups, with NPC-only groups exhibiting the highest
      anabolic gene expression levels. However, NPC-only constructs also responded to
      inflammation and hypoxia with significant upregulation of catabolic genes (MMP-1,
      MMP-9, MMP-13, and ADAMTS-5). MSC-only groups were unaffected by degenerative
      media conditions, and co-culture with MSCs modulated catabolic induction of the
      NPCs. Culturing cells in a micropellet configuration dramatically reduced
      catabolic induction in co-culture and NPC-only groups. Co-culture micropellets,
      which take advantage of both cell type and configuration effects, had the most
      immunomodulatory response, with a significant decrease in MMP-13 and ADAMTS-5
      expression in hypoxic and inflammatory media conditions. Co-culture micropellets
      were also found to self-organize into bilaminar formations with an MSC core and
      NPC outer layer. Further understanding of these cell type and configuration
      effects can improve tissue engineering designs. (c) 2016 The Authors. Journal of
      Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the
      Orthopaedic Research Society. J Orthop Res 35:61-73, 2017.

PMID- 27699838
TI  - Biomarkers of exposure to nanosilver and silver accumulation in yellow perch
      (Perca flavescens).
AB  - There is a risk of exposure of aquatic organisms to silver nanoparticles (AgNPs)
      from discharges of municipal and industrial wastewater. In the present study,
      yellow perch (Perca flavescens) were exposed to environmentally relevant
      concentrations (1 mg/L and 100 mg/L) of AgNPs and silver ions (Ag+ ) in static
      renewal experiments conducted over 96 h and 10 d. The greatest accumulation of
      total Ag occurred in the liver of P. flavescens, and there was >10-fold more
      accumulation in the treatments with Ag+ relative to the AgNP treatments. Residues
      of total Ag increased with concentration and duration of exposure in liver, gill,
      and muscle. Both exposures caused a 2-fold induction of gene expression for
      metallothionein (mt) in liver tissue after 96 h of exposure and reductions in
      levels of oxidized glutathione (GSSG) in liver after 10 d of exposure. Both AgNPs
      and Ag+ decreased the expression of heat-shock proteins (hsp70). Exposure to the
      high concentration of AgNPs for 10 d significantly increased lipid peroxidation
      in gill tissue, as indicated by the thiobarbituric acid reactive substances
      (TBARS) assay. There was a negative correlation between mean levels of GSSG and
      TBARS for both gill and liver tissue when data for all treatments were combined.
      It is significant that these biological responses were observed in P. flavescens
      exposed to AgNPs, even though accumulation of total Ag was at least 10-fold lower
      relative to the treatments with Ag+ . Environ Toxicol Chem 2017;36:1211-1220. (c)
      2016 SETAC.

PMID- 27699839
TI  - Epidemiologic Analysis of Onychomycosis in the San Diego Pediatric Population.
AB  - BACKGROUND: Onychomycosis (OM) is thought to be a rare disease in children,
      although there are few epidemiologic studies. METHODS: This 3-year retrospective
      case series of nearly 400 children seen at Rady Children's Hospital-San Diego
      (RCHSD) describes the characteristics of OM found in this pediatric population.
      RESULTS: From 2011 to 2013, the Pediatric and Adolescent Dermatology Clinic at
      RCHSD saw a total of 36,634 unique patients, of whom 433 were unique patients
      with OM. Thirty-four patients met exclusion criteria, leaving 399 (1.1%) with a
      diagnosis of OM by a pediatric dermatologist. Nail cultures were obtained in 242
      cases (60.7%), 116 (48.0%) of which were positive. Trichophyton rubrum was the
      most commonly isolated pathogen, responsible for 106 cases (91.3%) of positive
      cultures in the cohort. CONCLUSIONS: Our study provides important regional
      information regarding epidemiologic data in pediatric onychomycosis, highlighting
      the diagnostic methods most commonly used and the pathogens most frequently
      encountered in our practice.

PMID- 27699840
TI  - A semiautomatic method for rapid segmentation of velocity-encoded myocardial
      magnetic resonance imaging data.
AB  - PURPOSE: To develop a semiautomatic method for rapid segmentation of myocardial
      tissue phase mapping (TPM) data. METHODS: Manual segmentation of the myocardium
      was performed at end-diastole and end-systole. The points in both user-defined
      masks were then automatically tracked over the entire cardiac cycle using
      temporal integration of the velocity field. Paths that failed to visit both masks
      at the expected times were excluded, after which masks for all time points were
      generated automatically from the accepted paths. Midventricular and basal phase
      contrast TPM slices from 12 rats were segmented using the proposed method and
      fully manual segmentation. The results were compared using Dice's metric and
      Bland-Altman analysis, and interobserver variability was assessed. RESULTS: The
      semiautomatic method reduced the average user input time from 21 min to 1 min per
      slice. The Dice metrics between the methods were 0.88 +/- 0.03 (midventricular)
      and 0.83 +/- 0.06 (basal), and Bland-Altman limits of agreement of peak systolic
      and diastolic regional velocities were: midventricular: 0.05 +/- 0.65 cm/s, -0.02
      +/- 0.42 cm/s, and -0.03 +/- 0.40 cm/s (radial, tangential, longitudinal); basal:
      -0.04 +/- 0.73 cm/s, 0.03 +/- 0.60 cm/s, and -0.04 +/- 0.48 cm/s (radial,
      tangential, longitudinal). Interobserver variability following semiautomatic
      segmentation was lower than for manual segmentation. CONCLUSION: The proposed
      method reduced the segmentation time substantially and exhibited well-preserved
      data quality and excellent interobserver limits of agreement. Magn Reson Med
      78:1199-1207, 2017. (c) 2016 International Society for Magnetic Resonance in
      Medicine.

PMID- 27699842
TI  - Percutaneous versus surgical cut-down access in transfemoral transcatheter aortic
      valve replacement: A meta-analysis.
AB  - BACKGROUND: The transfemoral (TF) approach has become the preferred approach for
      transcatheter aortic valve replacement (TAVR) because of its low risk profile.
      However, the relative safety of the percutaneous approach (PC) compared to
      surgical cut-down (SC) remains unclear. Our aim was to compare the outcomes
      between PC versus SC access in patients undergoing TF-TAVR using a meta-analysis.
      METHODS: We conducted a systematic electronic database search for studies
      reporting major and minor vascular complications (VC), major and minor bleeding,
      and perioperative all-cause mortality, in PC versus SC TF-TAVR cases.
      Complications were reported based on the Valve Academic Research Consortium
      criteria. A random-effects model was used to calculate odds ratios and 95%
      confidence intervals. RESULTS: Eight observational cohort studies and one
      randomized control trial (2513 patients in PC and 1767 patients in SC) were
      included in the analysis. Major and minor VC, as well as bleeding complications,
      were comparable between the two approaches. The need for surgical intervention
      for VC was comparable between PC and SC. There was no difference in perioperative
      all-cause mortality. CONCLUSIONS: PC and SC have similar safety profiles and
      outcomes when used appropriately in selected patients.

PMID- 27699841
TI  - Combining rheology and MRI: Imaging healthy and tumorous brains based on
      mechanical properties.
AB  - PURPOSE: It is well known that pathological changes in tissue alter its
      mechanical properties. This holds also true for brain tissue. In case of the
      brain, however, obtaining information about these properties is hard due to the
      surrounding cranial bone. In this paper a novel technique to create an imaging
      contrast based on the aforementioned properties is presented. METHODS: The method
      is based on an excitation of the brain induced by a short fall. The response of
      the brain tissue is measured using a motion sensitive MRI sequence. RESULTS: The
      new method is tested by measurements on phantom material as well as on healthy
      volunteers. In a proof of principle experiment the capability of the approach to
      identify local alterations in the mechanical properties is shown by means of
      measurements on meningioma patients. CONCLUSION: The presented results show the
      feasibility of the novel method. Even in this early state of the proposed method,
      comparisons of measurements on meningioma patients with intraoperative palpation
      suggest that meningioma tissue responds differently to the excitation depending
      on their mechanical properties. Magn Reson Med 78:930-940, 2017. (c) 2016
      International Society for Magnetic Resonance in Medicine.

PMID- 27699843
TI  - Quantitative ultrashort TE imaging of the short-T2 components in skeletal muscle
      using an extended echo-subtraction method.
AB  - PURPOSE: To introduce an ultrashort echo time (UTE) based method for quantitative
      mapping of short-T2 signals in skeletal muscle (SKM) in the presence of fat, with
      the aim of monitoring SKM fibrosis. METHODS: From a set of at least five UTE
      images of the same slice, a long- T2* map, a fat-fraction map, and a map of short
      T2 -signal fraction are extracted. The method was validated by numerical
      simulations and in vitro studies on collagen solutions. Finaly, the method was
      applied to image the short-T2 signals in the leg of eight healthy volunteers.
      RESULTS: The imaged short-T2 -signal fractions in the collagen solutions
      correlated with their respective collagen concentrations ( R=0.999,  P=0.009).
      Short-T2 tissues such as cortical bone and fasciae were highlighted in the
      resulting short-T2 fraction maps. A significant fraction of short-T2 signal was
      systematically observed in the skeletal muscle of all of the subjects (4.5+/
      1.2%). CONCLUSION: The proposed method allows the quantitative imaging of short
      T2 components in tissues containing fat. By also having the fat-fraction and T2*
      maps as outcomes, long-T2 suppression is accomplished without requiring
      modifications to the basic UTE sequence. Although the hypersignal observed in the
      fasciae suggests that the short-T2 signal observed in SKM might arise from
      interstitial connective tissue, further investigation is necessary to confirm
      this statement. Magn Reson Med 78:997-1008, 2017. (c) 2016 International Society
      for Magnetic Resonance in Medicine.

PMID- 27699844
TI  - Specialized volumetric thermometry for improved guidance of MRgFUS in brain.
AB  - PURPOSE: MR thermometry is critical for safe and effective transcranial focused
      ultrasound. The current single-slice MR thermometry sequence cannot achieve all
      desired treatment monitoring requirements. We propose an approach in which the
      imaging requirements of different aspects of treatment monitoring are met by
      optimizing multiple sequences. METHODS: Imaging requirements were determined for
      three stages of MR-guided focused ultrasound brain treatment: 1) focal spot
      localization, 2) focal spot monitoring, and 3) background monitoring. Multiple
      echo spiral thermometry sequences were optimized for each set of requirements and
      then validated with in vivo signal-to-noise ratio measurements and with phantom
      heating experiments. RESULTS: Each of the proposed sequences obtained better
      precision than the current two-dimensional Fourier transform (2DFT) thermometry
      sequence. Five-slice focal spot localization achieved two-fold better resolution
      with 1.9-fold better precision but two-fold longer acquisition compared to 2DFT.
      Five-slice focal monitoring achieved 2.1-fold better precision with similar speed
      but 12% larger voxels than 2DFT. Full-brain background monitoring was
      demonstrated in both axial (7.1 s) and sagittal (11.4 s) orientations. Phantom
      heating time curves were consistent across all sequences after correcting for
      resolution. CONCLUSION: Multiple-echo spiral imaging significantly improves MR
      thermometry efficiency, enabling multiple-slice monitoring. Optimizing multiple
      specialized sequences provides better performance than can be achieved by any
      single sequence. Magn Reson Med 78:508-517, 2017. (c) 2016 International Society
      for Magnetic Resonance in Medicine.

PMID- 27699846
TI  - Treatment of Childhood Vitiligo Using Tacrolimus Ointment with Narrowband
      Ultraviolet B Phototherapy.
AB  - BACKGROUND/OBJECTIVES: A combination of narrowband ultraviolet B (NBUVB)
      phototherapy plus topical tacrolimus has been used in adult vitiligo but has not
      yet been explored in children. We therefore sought to highlight the efficacy of
      this synergistic combination in childhood vitiligo. The objective was to study
      the clinical efficacy and safety of a combination of NBUVB with topical
      tacrolimus ointment 0.03% in childhood vitiligo. METHOD: In this open-label
      study, 20 children, 4 to 14 years of age, with symmetrical vitiligo lesions were
      enrolled for 24 weeks. All were instructed to apply tacrolimus ointment 0.03% on
      a target patch on the left side of the body twice daily and no topical on a
      target patch on the right side. The whole body was irradiated with NBUVB three
      times per week. All patients were examined and the same dermatologist
      photographed lesions to assess for repigmentation at 4-week intervals. Response
      was noted as the percentage of repigmentation (none, 0%; poor, 1-25%; moderate,
      26-50%; good, 51-75%; excellent, >75%). RESULT: Our study found a statistically
      significant difference in the mean percentage of repigmentation at 4 and 6 months
      between combination therapy and NBUVB monotherapy. The mean cumulative dose and
      average number of exposures for the first clinically visible response were
      significantly lower with combination therapy. No serious adverse events were
      noted during the study period. CONCLUSION: Our preliminary data suggest that a
      combination of NBUVB phototherapy with topical tacrolimus is a highly effective
      and promising therapeutic option for vitiligo in children, whose treatment
      options are very limited, but long-term studies are needed to evaluate the future
      risk of malignancy.

PMID- 27699845
TI  - Management of older adults with dementia who present to emergency services with
      neuropsychiatric symptoms.
AB  - OBJECTIVE: Our aim is to evaluate if and how neuropsychiatric symptoms (NPS) of
      dementia influence the management and disposition of older adults who present to
      emergency care settings. METHODS: This is a retrospective cohort study that
      involved the medical and psychiatric emergency departments of a tertiary academic
      medical center. Participants included patients >=65 years of age with dementia
      who presented between 1 February 2012 and 16 July 2014 (n = 347). Subjects with
      documented NPS (n = 78) were compared with a group of subjects without documented
      NPS (n = 78) randomly selected from the overall group with dementia. The groups
      with and without NPS were compared on demographic, clinical, management, and
      disposition characteristics. RESULTS: Patients with NPS were more likely to have
      additional diagnostic testing performed and receive psychotropic medications
      including benzodiazepines and antipsychotics. Significantly fewer patients with
      NPS (59.0%) returned to their original setting from the emergency department than
      patients without NPS (76.9%). Among patients with NPS, those who had a motor
      disturbance were more likely to receive psychotropic medications than patients
      who did not have a motor disturbance. Depression/dysphoria, anxiety,
      disinhibition, irritability/lability, and motor disturbance were all associated
      with transfer from medical to psychiatric emergency department. Patients with
      depression/dysphoria or anxiety were more likely to be psychiatrically
      hospitalized. CONCLUSIONS: There are significant differences in the management of
      dementia with and without NPS in the emergency room setting. Developing and
      implementing successful methods to manage NPS in the emergency department and
      outpatient setting could potentially lead to less emergent psychotropic
      administration and reduce hospitalizations. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 27699847
TI  - Detecting the native ligand orientation by interfacial rigidity: SiteInterlock.
AB  - Understanding the physical attributes of protein-ligand interfaces, the source of
      most biological activity, is a fundamental problem in biophysics. Knowing the
      characteristic features of interfaces also enables the design of molecules with
      potent and selective interactions. Prediction of native protein-ligand
      interactions has traditionally focused on the development of physics-based
      potential energy functions, empirical scoring functions that are fit to binding
      data, and knowledge-based potentials that assess the likelihood of pairwise
      interactions. Here we explore a new approach, testing the hypothesis that protein
      ligand binding results in computationally detectable rigidification of the
      protein-ligand interface. Our SiteInterlock approach uses rigidity theory to
      efficiently measure the relative interfacial rigidity of a series of small
      molecule ligand orientations and conformations for a number of protein complexes.
      In the majority of cases, SiteInterlock detects a near-native binding mode as
      being the most rigid, with particularly robust performance relative to other
      methods when the ligand-free conformation of the protein is provided. The
      interfacial rigidification of both the protein and ligand prove to be important
      characteristics of the native binding mode. This measure of rigidity is also
      sensitive to the spatial coupling of interactions and bond-rotational degrees of
      freedom in the interface. While the predictive performance of SiteInterlock is
      competitive with the best of the five other scoring functions tested, its measure
      of rigidity encompasses cooperative rather than just additive binding
      interactions, providing novel information for detecting native-like complexes.
      SiteInterlock shows special strength in enhancing the prediction of native
      complexes by ruling out inaccurate poses. Proteins 2016; 84:1888-1901. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27699848
TI  - Total mercury and methylmercury concentrations over a gradient of contamination
      in earthworms living in rice paddy soil.
AB  - Mercury (Hg) deposited from emissions or from local contamination, can have
      serious health effects on humans and wildlife. Traditionally, Hg has been seen as
      a threat to aquatic wildlife, because of its conversion in suboxic conditions
      into bioavailable methylmercury (MeHg), but it can also threaten contaminated
      terrestrial ecosystems. In Asia, rice paddies in particular may be sensitive
      ecosystems. Earthworms are soil-dwelling organisms that have been used as
      indicators of Hg bioavailability; however, the MeHg concentrations they
      accumulate in rice paddy environments are not well known. Earthworm and soil
      samples were collected from rice paddies at progressive distances from abandoned
      mercury mines in Guizhou, China, and at control sites without a history of Hg
      mining. Total Hg (THg) and MeHg concentrations declined in soil and earthworms as
      distance increased from the mines, but the percentage of THg that was MeHg, and
      the bioaccumulation factors in earthworms, increased over this gradient. This
      escalation in methylation and the incursion of MeHg into earthworms may be
      influenced by more acidic soil conditions and higher organic content further from
      the mines. In areas where the source of Hg is deposition, especially in water
      logged and acidic rice paddy soil, earthworms may biomagnify MeHg more than was
      previously reported. It is emphasized that rice paddy environments affected by
      acidifying deposition may be widely dispersed throughout Asia. Environ Toxicol
      Chem 2017;36:1202-1210. (c) 2016 SETAC.

PMID- 27699849
TI  - Bilateral congenital coronary ostial obstruction: Exertional syncope in an
      otherwise healthy 8-year-old.
AB  - Congenital stenosis/atresia of a coronary artery is an exquisitely rare anomaly
      (Congenit Heart Dis, 2, 2007, 347) with increased risk of sudden death. Bilateral
      coronary obstruction is even more unusual but has been reported in conjunction
      with aortic valve disease, syphilis, and Takayasu's arteritis. To the best of our
      knowledge, obstruction of both coronaries in a pediatric patient has only been
      reported once (Ann Thorac Surg, 55, 1993, 1564). We present a patient with an
      intramural, anomalous aortic origin of the right coronary artery from the
      contralateral sinus (AAORCA) with near atresia of the left main coronary ostium.
      The diagnosis was made by echocardiogram and confirmed by catheterization and
      magnetic resonance imaging.

PMID- 27699850
TI  - Real time three-dimensional transesophageal echocardiography imaging of crescent
      shaped superior sinus venosus atrial septal defect.
AB  - Multi-imaging modalities should be considered in patients with atrial septal
      defects (ASDs) in which the degree of right ventricular enlargement is not fully
      explained by the small size of ASD found on conventional transthoracic
      echocardiography. We report a case of crescent-shaped superior sinus venosus ASD
      discriminated using real-time three-dimensional transesophageal echocardiography.
      MDCT confirmed its relationship with the superior vena cava and the absence of
      combined anomalies, such as the pulmonary venous return anomaly.

PMID- 27699851
TI  - Cinnamon Sugar Scrub Dermatitis: "Natural" Is Not Always Best.
AB  - Children are at risk of developing allergic contact dermatitis to fragrances.
      Personal hygiene products, even those labeled hypoallergenic or considered all
      natural, may be a significant source of fragrance exposure in this population.

PMID- 27699852
TI  - True morphology of mitral regurgitant flow assessed by three-dimensional
      transesophageal echocardiography.
AB  - INTRODUCTION: Quantification of mitral regurgitation (MR) by two-dimensional (2D)
      transthoracic echocardiography (TTE) is based on the analysis of the proximal
      flow convergence (PFC) and the "vena contracta" (VC). This method assumes
      geometries and can be misleading. In contrast, three-dimensional (3D)
      echocardiography directly measures flow volumes and does not assume geometries,
      which allows for more accurate MR evaluation. AIMS: To report the 3D
      transesophageal echocardiography (3DTEE) feasibility for MR quantification and
      evaluate its concordance with 2D echo. METHODS: Twenty-seven consecutive patients
      undergoing 2D and 3DTEE for presurgical MR evaluation were studied prospectively.
      MR quantification was performed by classical 2D methods based on PFC. Diameters
      of the VC in orthogonal planes by 3DTEE were estimated, establishing the VC
      sphericity index as well as VC area (VCA) by direct planimetry. In case of
      multiple jets, we calculated the sum of the VCA. RESULTS: MR assessment by 3DTEE
      was feasible. An adequate concordance between VC measurements by 2D methods (TTE
      and TEE) was observed; however, there was a poor correlation when compared with
      3DTEE. The sphericity index of the VC was: 2.08 (+/-0. 72), reflecting a
      noncircular VC. CONCLUSIONS: 3DTEE is a feasible method for the assessment of the
      MR true morphology, allowing a better quantification of MR without assuming any
      geometry. This method revealed the presence of multiple jets, potentially
      improving MR evaluation and leading to changes in medical decision when compared
      to 2D echo assessment.

PMID- 27699853
TI  - Atypical echocardiographic findings in traumatic aortic transection.
AB  - Aortic rupture and transection are constituents of the acute aortic syndrome.
      Injury to the thoracic aorta during motor vehicle crashes is associated with
      blunt chest trauma and rapid deceleration mechanisms. Type A dissections and/or
      rupture of the aorta at the level of the aortic isthmus are the more common
      presentations of aortic injuries associated with motor vehicle crashes. We
      present the case of atypical echocardiographic findings of a nearly complete
      circumferential transection of the proximal ascending aorta injury after a
      motorcycle crash.

PMID- 27699854
TI  - Proximal ulnar artery aneurysm following a Bentall procedure for type A aortic
      dissection.
AB  - Non-traumatic or infective peripheral aneurysms of the upper extremities are
      rare. We report a case of an aneurysm involving the left proximal ulnar artery
      leading to upper limb ischemia in a patient following a Bentall procedure for a
      type A dissection.

PMID- 27699857
TI  - Phaeochromocytoma presenting with labile blood pressures following coronary
      artery bypass grafting.
AB  - Pheochromocytomas have been reported prior to and during coronary artery bypass
      surgery. We present a patient with an undiagnosed pheochromocytoma who presented
      with labile hypertension following coronary artery bypass surgery. This case
      calls attention to the inclusion of an undiagnosed pheochromocytoma in the
      differential diagnosis for all patients who develop labile hypertension in the
      postoperative period following cardiac surgery.

PMID- 27699855
TI  - A multi-resolution model to capture both global fluctuations of an enzyme and
      molecular recognition in the ligand-binding site.
AB  - In multi-resolution simulations, different system components are simultaneously
      modeled at different levels of resolution, these being smoothly coupled together.
      In the case of enzyme systems, computationally expensive atomistic detail is
      needed in the active site to capture the chemistry of ligand binding. Global
      properties of the rest of the protein also play an essential role, determining
      the structure and fluctuations of the binding site; however, these can be modeled
      on a coarser level. Similarly, in the most computationally efficient scheme only
      the solvent hydrating the active site requires atomistic detail. We present a
      methodology to couple atomistic and coarse-grained protein models, while
      solvating the atomistic part of the protein in atomistic water. This allows a
      free choice of which protein and solvent degrees of freedom to include
      atomistically. This multi-resolution methodology can successfully model stable
      ligand binding, and we further confirm its validity by exploring the reproduction
      of system properties relevant to enzymatic function. In addition to a
      computational speedup, such an approach can allow the identification of the
      essential degrees of freedom playing a role in a given process, potentially
      yielding new insights into biomolecular function. Proteins 2016; 84:1902-1913.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27699856
TI  - Determination of binding affinity upon mutation for type I dockerin-cohesin
      complexes from Clostridium thermocellum and Clostridium cellulolyticum using deep
      sequencing.
AB  - The comprehensive sequence determinants of binding affinity for type I cohesin
      toward dockerin from Clostridium thermocellum and Clostridium cellulolyticum was
      evaluated using deep mutational scanning coupled to yeast surface display. We
      measured the relative binding affinity to dockerin for 2970 and 2778 single point
      mutants of C. thermocellum and C. cellulolyticum, respectively, representing over
      96% of all possible single point mutants. The interface DeltaDeltaG for each
      variant was reconstructed from sequencing counts and compared with the three
      independent experimental methods. This reconstruction results in a narrow dynamic
      range of -0.8-0.5 kcal/mol. The computational software packages FoldX and Rosetta
      were used to predict mutations that disrupt binding by more than 0.4 kcal/mol.
      The area under the curve of receiver operator curves was 0.82 for FoldX and 0.77
      for Rosetta, showing reasonable agreements between predictions and experimental
      results. Destabilizing mutations to core and rim positions were predicted with
      higher accuracy than support positions. This benchmark dataset may be useful for
      developing new computational prediction tools for the prediction of the
      mutational effect on binding affinities for protein-protein interactions.
      Experimental considerations to improve precision and range of the reconstruction
      method are discussed. Proteins 2016; 84:1914-1928. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27699859
TI  - Acne Fulminans: Case Series and Review of the Literature.
AB  - Acne fulminans (AF) is a rare manifestation and the most severe form of the
      entire clinical spectrum of acne. The disease is destructive and is characterized
      by the sudden onset of painful and ulcerative pustules and systemic symptoms
      including high fever, hepatomegaly, polyarthralgia, leukocytosis, plaquetose, and
      increased inflammatory markers and transaminases. Osteolytic lesions in multiple
      skeletal sites could also be associated. The use of isotretinoin is considered a
      related trigger, as well as the use and cessation of testosterone, although a
      bacterial infection, a drug-induced disease, or an intake of anabolic androgenic
      steroids has been suggested. The treatment of AF is challenging and
      controversial. The recommended treatment is aggressive and consists of a
      combination of oral steroids and low doses of isotretinoin, with no consensus at
      this time. The patient may require several weeks of hospitalization to control
      the eruption. The cutaneous lesions usually leave scars and milia. We report on
      two boys and two girls presenting with AF, triggered by isotretinoin in three
      patients and by an antibiotic in one patient. All the patients treated with
      corticosteroids and isotretinoin with success.

PMID- 27699860
TI  - Angioedema After Squaric Acid Treatment in a 6-Year-Old Girl.
AB  - Alopecia areata (AA) involves the immune-related destruction of hair follicles,
      resulting in patches of complete hair loss, most often on the scalp. The topical
      sensitizer squaric acid dibutylester (SADBE) is a popular treatment option given
      its low side-effect profile, hair regrowth potential, and lack of cross
      reactivity with other chemicals. We describe a unique case of a 6-year-old girl
      who developed angioedema after SADBE treatment for AA.

PMID- 27699858
TI  - Genetic association between RAGE polymorphisms and Alzheimer's disease and Lewy
      body dementias in a Japanese cohort: a case-control study.
AB  - BACKGROUND/AIMS: Interaction of receptor for advanced glycation end products
      (RAGE) with amyloid-beta increases amplification of oxidative stress and plays
      pathological roles in Alzheimer's disease (AD). Oxidative stress leads to alpha
      synuclein aggregation and is also a major contributing factor in the pathogenesis
      of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE
      gene polymorphisms were associated with AD and LBDs. METHODS: Four single
      nucleotide polymorphisms (SNPs)-rs1800624, rs1800625, rs184003, and rs2070600-of
      the gene were analyzed using a case-control study design comprising 288 AD
      patients, 76 LBDs patients, and 105 age-matched controls. RESULTS: Linkage
      disequilibrium (LD) examination showed strong LD from rs1800624 to rs2070600 on
      the gene (1.1 kb) in our cases in Japan. Rs184003 was associated with an
      increased risk of AD. Although there were no statistical associations for the
      other three SNPs, haplotypic analyses detected genetic associations between AD
      and the RAGE gene. Although relatively few cases were studied, results from the
      SNPs showed that they did not modify the risk of developing LBDs in the Japanese
      population. CONCLUSION: Our findings suggested that polymorphisms in the RAGE
      gene are involved in genetic susceptibility to AD. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27699861
TI  - Pediatric Pyoderma Gangrenosum: A Retrospective Review of Clinical Features,
      Etiologic Associations, and Treatment.
AB  - BACKGROUND/OBJECTIVES: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis
      rarely seen in children. Its features have not been well characterized in
      children. We sought to characterize the clinical features, etiologic
      associations, and treatment of PG in children younger than 18 years. METHODS: We
      performed a retrospective review of children younger than 18 years with PG at the
      Mayo Clinic from January 1976 to August 2013. RESULTS: Thirteen children with PG
      were identified (n = 8; 62% female). All had ulcerations, with 62% having
      pustular lesions. Sites of involvement included the trunk (77%), lower
      extremities (77%), upper extremities (38%), and head and neck (38%). Nine (69%)
      had an underlying comorbidity, including seven with Crohn's disease (54%), one
      with juvenile idiopathic arthritis (8%), and one with pyogenic arthritis,
      pyoderma gangrenosum, and acne syndrome (8%). Treatments included topical or
      local care (92%) and systemic therapies (85%) such as oral corticosteroids (62%)
      and sulfasalazine or related 5-aminosalicylate drugs (46%). The clinical course
      did not correlate with that of the underlying systemic disease and response to
      treatment varied. CONCLUSION: Pediatric PG has a more varied anatomic
      distribution and a greater predominance of pustular lesions than PG in adults and
      a strong association with inflammatory bowel disease.

PMID- 27699862
TI  - Lumbar Sympathetic Pulsed Radiofrequency Treatment for Primary Erythromelalgia: A
      Case Report.
AB  - Erythromelalgia is often refractory and resistant to many forms of treatment.
      Numerous therapeutic options have been tried, but effective treatment remains
      elusive. The sympathetic nervous system has been involved in various painful
      conditions of neuropathic, vascular, and visceral origin. Sympathetic block is
      helpful in making a diagnosis and managing pain. We report a case of excellent
      pain relief after lumbar sympathetic pulsed radiofrequency treatment in a patient
      with primary erythromelalgia of the lower extremities. This case suggests the
      viability of pulsed radiofrequency treatment in patients with erythromelalgia.

PMID- 27699863
TI  - Budesonide foam for mild to moderate distal ulcerative colitis: A systematic
      review and meta-analysis.
AB  - BACKGROUND AND AIM: Budesonide is a second-generation steroid with prominent
      topical effects and minimal systemic activity for patients with ulcerative
      colitis (UC). We perform a systematic review and meta-analysis of randomized
      placebo-controlled trials to assess the efficacy and safety of budesonide foam in
      mild-to-moderate distal UC. METHODS: Comprehensive searches were performed to
      identify all eligible studies. Outcome measures were clinical remission,
      endoscopic improvement, elimination of rectal bleeding, and adverse events. The
      risk ratio (RR) with 95% confidence interval (CI) was estimated for each outcome.
      All statistical analyses were performed in STATA 12.0. RESULTS: Three randomized
      placebo-controlled trials recruiting 711 patients with mild-to-moderate distal UC
      were included in this study. No significant bias and heterogeneity was
      identified. Pooled analyses showed that budesonide foam was significantly
      superior to placebo for induction of clinical remission (RR = 1.83, 95%CI: 1.41,
      2.37; P < 0.001) and endoscopic improvement (RR = 1.44, 95%CI: 1.23, 1.68; P <
      0.001), and eliminating rectal bleeding at week 2 (RR = 2.00, 95%CI: 1.50, 2.66;
      P < 0.001), week 4 (RR = 1.73, 95%CI: 1.42, 2.12; P < 0.001), and week 6 (RR =
      1.76, 95%CI: 1.45, 2.14; P < 0.001). No statistically significant difference was
      observed in the incidence of treatment-related adverse events and therapeutic
      discontinuation because of adverse events between budesonide foam and placebo.
      CONCLUSIONS: Budesonide foam is well tolerated and superior to placebo in
      inducing clinical remission and endoscopic improvement, and eliminating rectal
      bleeding for mild-to-moderate distal UC.

PMID- 27699864
TI  - Retrospective Study of Nasal Infantile Hemangiomas: Characteristics,
      Complications, and Outcomes.
AB  - BACKGROUND/OBJECTIVES: Nasal infantile hemangiomas (IHs) pose serious medical
      complications and psychosocial stress if tumor involution is incomplete or
      prolonged. The objective was to determine which IH characteristics are associated
      with complications and are predictive of outcome, assessed as the presence of IHs
      or residual skin changes upon kindergarten entry, to better manage these lesions
      and counsel families. METHODS: A retrospective chart review of all patients seen
      in the Division of Pediatric Dermatology at Johns Hopkins Medicine between 2001
      and 2014 for nasal IHs (N = 89) was performed. A follow-up telephone interview
      with parents was conducted in June and July 2014. RESULTS: Complications were
      observed in 39% of patients. Segmental and indeterminate IHs were more likely to
      have complications than focal IHs (p = 0.01). Mixed IHs were more likely to
      ulcerate than deep or superficial IHs (p = 0.01). Eighty percent of patients had
      treatment and 19% had surgery. Although IHs regressed by kindergarten entry in
      70% of patients, 78% of these patients had residual skin changes. Mixed and
      superficial IHs left more residua than deep IHs (p = 0.04). A statistical
      comparison of treatments with respect to outcome at kindergarten entry could not
      be made because subgroups were too small and heterogeneous. CONCLUSION: Nasal IHs
      had higher rates of complications and treatment than previous reports of IHs at
      all body sites. Lesions of segmental and indeterminate type and mixed depth
      should be identified as high risk and treated accordingly. Parents may be
      counseled that most nasal IHs involute by kindergarten but leave residua and that
      early referral for treatment may be important for the best outcome.

PMID- 27699865
TI  - Personality and behavioural changes do not precede memory problems as possible
      signs of dementia in ageing people with Down syndrome.
AB  - OBJECTIVE: The objective was to find out whether changes in personality and
      adaptive functioning or memory processes decline first in ageing people with Down
      syndrome. METHODS: We measured these variables cross-sectionally in a Dutch
      sample (22 to 62 years of age) of 68 institutionalised people with Down syndrome.
      RESULTS: The scores on all the variables except one of the temperament scales
      were found to decline gradually with increasing age, but deterioration of
      episodic memory started earlier. CONCLUSIONS: We argued that a subset of our
      sample suffered from dementia. Furthermore, the data suggested that immediate
      memory impairment is one of the earliest signs of the disease in people with Down
      syndrome, just as it is in the general population. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27699866
TI  - Influences of bicarbonate on processes of enamel subsurface remineralization and
      demineralization: assessment using micro-Raman spectroscopy and transverse
      microradiography.
AB  - In the present study, we investigated, using micro-Raman spectroscopy (Raman) and
      transverse microradiography, the influence of bicarbonate [sodium hydrogen
      carbonate (NaHCO3 )] on the effects of carbonate ions in the mineral phase during
      demineralization (acid resistance test) of subsurface lesions. Baseline lesions
      were created by demineralizing bovine enamel, and specimens were then exposed to
      remineralization solutions containing 0, 5, or 50 mM bicarbonate. Acid resistance
      tests were performed on remineralized and sound enamel specimens. Raman spectra
      showed that carbonate and phosphate were incorporated into both surface layers
      and lesion bodies during remineralization in the presence of bicarbonate.
      Moreover, the presence of bicarbonate did not affect the rates of
      remineralization, although the average mineral profiles of remineralized enamel
      differed from those of sound enamel after acid resistance tests. Raman analyses
      enabled close evaluation of site-specific characteristics of carbonate and
      phosphate in subsurface lesions. In conclusion, incorporation of carbonate and
      phosphate ions into enamel subsurface lesions during remineralization does not
      affect the magnitude of remineralization or acid resistance.

PMID- 27699869
TI  - Abstracts of the 25th Annual Meeting of the German Transplantation Society,
      Essen, Germany, 5-8 October 2016.

PMID- 27699867
TI  - A rapid and robust gradient measurement technique using dynamic single-point
      imaging.
AB  - PURPOSE: We propose a new gradient measurement technique based on dynamic single
      point imaging (SPI), which allows simple, rapid, and robust measurement of k
      space trajectory. METHODS: To enable gradient measurement, we utilize the
      variable field-of-view (FOV) property of dynamic SPI, which is dependent on
      gradient shape. First, one-dimensional (1D) dynamic SPI data are acquired from a
      targeted gradient axis, and then relative FOV scaling factors between 1D images
      or k-spaces at varying encoding times are found. These relative scaling factors
      are the relative k-space position that can be used for image reconstruction. The
      gradient measurement technique also can be used to estimate the gradient impulse
      response function for reproducible gradient estimation as a linear time invariant
      system. RESULTS: The proposed measurement technique was used to improve
      reconstructed image quality in 3D ultrashort echo, 2D spiral, and multi-echo
      bipolar gradient-echo imaging. In multi-echo bipolar gradient-echo imaging,
      measurement of the k-space trajectory allowed the use of a ramp-sampled
      trajectory for improved acquisition speed (approximately 30%) and more accurate
      quantitative fat and water separation in a phantom. CONCLUSION: The proposed
      dynamic SPI-based method allows fast k-space trajectory measurement with a simple
      implementation and no additional hardware for improved image quality. Magn Reson
      Med 78:950-962, 2017. (c) 2016 International Society for Magnetic Resonance in
      Medicine.

PMID- 27699870
TI  - Structures and recognition modes of toll-like receptors.
AB  - Toll-like receptors (TLRs) recognize common structural patterns in diverse
      microbial molecules and play central roles in the innate immune response. The
      structures of extracellular domains and their ligand complexes of several TLRs
      have been determined by X-ray crystallography. Here, we discuss recent advances
      on structures and activation mechanisms of TLRs. Despite the differences in
      interaction areas of ligand with TLRs, the extracellular domains of TLRs all
      adopt horseshoe-shaped structures and the overall M-shape of the TLR-ligand
      complexes is strikingly similar. The structural rearrangement information of TLRs
      sheds new light on their ligand-recognition and -activation mechanisms. Proteins
      2016; 85:3-9. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699868
TI  - Toward elucidating the heat activation mechanism of the TRPV1 channel gating by
      molecular dynamics simulation.
AB  - As a key cellular sensor, the TRPV1 cation channel undergoes a gating transition
      from a closed state to an open state in response to various physical and chemical
      stimuli including noxious heat. Despite years of study, the heat activation
      mechanism of TRPV1 gating remains enigmatic at the molecular level. Toward
      elucidating the structural and energetic basis of TRPV1 gating, we have performed
      molecular dynamics (MD) simulations (with cumulative simulation time of 3 MUs),
      starting from the high-resolution closed and open structures of TRPV1 solved by
      cryo-electron microscopy. In the closed-state simulations at 30 degrees C, we
      observed a stably closed channel constricted at the lower gate (near residue
      I679), while the upper gate (near residues G643 and M644) is dynamic and
      undergoes flickery opening/closing. In the open-state simulations at 60 degrees
      C, we found higher conformational variation consistent with a large entropy
      increase required for the heat activation, and both the lower and upper gates are
      dynamic with transient opening/closing. Through ensemble-based structural
      analyses of the closed state versus the open state, we revealed pronounced closed
      to-open conformational changes involving the membrane proximal domain (MPD)
      linker, the outer pore, and the TRP helix, which are accompanied by
      breaking/forming of a network of closed/open-state specific hydrogen bonds. By
      comparing the closed-state simulations at 30 degrees C and 60 degrees C, we
      observed heat-activated conformational changes in the MPD linker, the outer pore,
      and the TRP helix that resemble the closed-to-open conformational changes, along
      with partial formation of the open-state specific hydrogen bonds. Some of the
      residues involved in the above key hydrogen bonds were validated by previous
      mutational studies. Taken together, our MD simulations have offered rich
      structural and dynamic details beyond the static structures of TRPV1, and
      promising targets for future mutagenesis and functional studies of the TRPV1
      channel. Proteins 2016; 84:1938-1949. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699871
TI  - Mycosis fungoides two decades after exposure to sulphur mustard: a follow-up of
      1100 victims.
AB  - BACKGROUND: Sulphur mustard (SM) is an alkylating chemical warfare agent which
      causes acute and chronic injuries to the eyes, skin, lung and respiratory tract.
      OBJECTIVE: We aimed to investigate the relationship between SM poisoning and
      Mycosis fungoides (MF) as a late consequence. MATERIAL AND METHODS: In this
      retrospective study, the medical files of 1100 Iranian veterans confirmed to have
      exposure to SM agent during the Iraq-Iran war of the 1980s were reviewed.
      RESULTS: All 10 cases with MF were confirmed by clinical and histopathological
      examinations. The mean age of the studied subjects was 43.3 +/- 9.8 (years). In
      comparison to MF incidence rate in Iranian general population (0.39/100 000
      person-years), we found an incidence rate of 0.799/100 000 person-years for MF
      among those who had short-term exposure to SM. The most common sites for SM
      lesions were flexural and thin skin areas. The main limitation was the
      retrospective design. CONCLUSION: This study indicates that the risk of MF in
      those exposed to SM may increase over time. Therefore, their follow-up is
      recommended.

PMID- 27699872
TI  - Are myelodysplastic syndromes underdiagnosed in Poland? A report by the Polish
      Adult Leukaemia Group.
AB  - OBJECTIVES: The epidemiology of myelodysplastic syndromes (MDS) differs among
      countries. Here, we present the first epidemiological indices determined for
      Poland. METHODS: Twenty-one haematological centres participated in the study.
      Patients diagnosed with MDS and acute myeloid leukaemia (AML) with 20-29% blasts
      were enrolled. Data collection was conducted for strictly predefined period.
      RESULTS: The overall crude incidence rate for all MDS subtypes was 1.95 (95% CI,
      1.81-2.09) per 100 000 person-years: 2.46 (95% CI, 2.24-2.69) for males and 1.47
      (95% CI, 1.31-1.65) for females; after excluding AML cases, the indices were as
      follows: 2.35 (95% CI, 2.08-2.66) for males and 1.27 (95% CI, 1.08-1.5) for
      females. Prevalence rate was 6.2 per 100 000 persons (95% CI, 5.96-6.45), that is
      6.86 (95% CI, 6.49-7.24) for males and 5.58 (95% CI, 5.26-5.92) for females. Both
      incidence and prevalence increased with increasing age. The most frequently
      diagnosed MDS subtype was refractory cytopenia with multilineage dysplasia
      (RCMD), responsible for 30.3% of all newly diagnosed MDSs. CONCLUSIONS: RCMD is
      the most frequent MDS subtype in Poland. Incidence and prevalence indices are
      lower than those reported for other populations, which probably results from
      inadequate diagnosis of potential cases of this disease.

PMID- 27699873
TI  - Semen supplementation with palmitoleic acid promotes kinematics, microscopic and
      antioxidative parameters of ram spermatozoa during liquid storage.
AB  - The purpose of the present experiment was to investigate the protective effects
      of palmitoleate on the quality of ram semen during low temperature liquid
      storage. Ejaculates were collected using the artificial vagina from four Qezel
      rams twice a week. Ejaculates were pooled, diluted with Tris-egg yolk extender
      without palmitoleate (control) or supplemented with 0.125 (P 0.125), 0.25 (P
      0.25), 0.5 (P 0.5) and 1 (P 1) mM palmitoleate at a final concentration of 500 *
      106 spermatozoa/ml. Total motility and forward progressive motility (FPM) as well
      as other spermatozoa kinematics were evaluated by computer-assisted sperm
      analysis. Moreover, viability and membrane functionality were determined in the
      spermatozoa. Additionally, amounts of malondialdehyde (MDA), total antioxidant
      activity (AOA), nitric oxide (NO) and superoxide dismutase (SOD) activities were
      evaluated in the medium and spermatozoa at 0, 24, 48 and 72 hr of storage. The
      palmitoleate supplementation resulted in a significant (p < .05) increase in
      total motility and FPM with the highest increase at 0.5 mM concentration for 72
      hr. P 0.5 group also resulted in the highest percentage of membrane-intact
      spermatozoa (76.60 +/- 1.95%) and viability (75.81 +/- 1.34%) at 72 hr (p < .05).
      The amounts of MDA and NO were lower in P 0.125, P 0.25 and P 0.5 groups compared
      to control at 48 hr and 72 hr (p < .05). Higher amounts of AOA were obtained in
      palmitoleate-treated groups in medium and spermatozoa during storage time (p <
      .05). Furthermore, palmitoleate supplementation increased the SOD activities in
      spermatozoa compared to the control (p < .05). The results of the present
      experiment reveal that supplementation with 0.5 mM palmitoleate improves ram
      spermatozoa motion characteristics, AOA levels and SOD activities during liquid
      storage. Then, palmitoleate could be used as an antioxidant source during liquid
      storage of ram semen.

PMID- 27699874
TI  - Extended pelvic lymph node dissection at radical cystectomy for bladder cancer
      improves survival: Results of a nationwide population-based study.

PMID- 27699875
TI  - Tomoelastography of the abdomen: Tissue mechanical properties of the liver,
      spleen, kidney, and pancreas from single MR elastography scans at different
      hydration states.
AB  - PURPOSE: To develop a compact magnetic resonance elastography (MRE) protocol for
      abdomen and to investigate the effect of water uptake on tissue stiffness in the
      liver, spleen, kidney, and pancreas. METHODS: Nine asymptomatic volunteers were
      investigated by MRE before and after 1 liter water uptake. Shear-wave excitation
      at four frequencies was transferred to the abdomen from anterior and posterior
      directions using pressurized air drivers. Tomographic representations of shear
      wave speed were produced by analysis of multifrequency wave numbers in axial and
      coronal images acquired within four breath-holds or under free breathing,
      respectively. RESULTS: Pre and post water, stiffness of the spleen (pre/post:
      2.20 +/- 0.10/2.06 +/- 0.18 m/s) and kidney (pre/post: 1.93 +/- 0.22/1.97 +/-
      0.23 m/s) was higher than in the liver (pre/post: 1.36 +/- 0.10/1.38 +/- 0.13
      m/s) and pancreas (pre/post: 1.20 +/- 0.12/1.20 +/- 0.08 m/s), all P < 0.01.
      Accounting for four drive frequencies, water drinking only changed the splenic
      stiffness (-6%, P = 0.03), whereas in the frequency range from 50 to 60 Hz the
      effect became significant also in the pancreas (-6%, P = 0.04) and liver (+3%, P
      = 0.03). Elastograms of the kidney in coronal view clearly depicted higher
      stiffness in cortex than in medulla. CONCLUSION: Tomoelastography reveals
      sensitivity of tissue mechanical properties to the hydration state of multiple
      abdominal organs within one scan and in unprecedented resolution of anatomical
      details. Magn Reson Med 78:976-983, 2017. (c) 2016 International Society for
      Magnetic Resonance in Medicine.

PMID- 27699876
TI  - Estimating Time-averaged Serum Urea Nitrogen Concentration during Various Urine
      Collection Periods: A Prediction Equation for Thrice Weekly and Biweekly Dialysis
      Schedules.
AB  - Residual kidney urea clearance in dialysis patients typically is calculated as
      the per minute excretion of urea nitrogen, obtained during the 24-48 hour
      collection period that usually ends just prior to a dialysis session, divided by
      the time-averaged serum water urea nitrogen concentration during the collection
      period. This concentration is difficult to estimate unless a formal kinetic
      modeling program is being used. We used a urea kinetic modeling program to derive
      an equation to estimate the time-averaged serum water concentration during urine
      collection periods of various lengths collected during various interdialytic
      intervals, for 3/week or 2/week dialysis schedules. The equation to predict time
      averaged serum water urea nitrogen concentration during the collection period was
      a function of the ratio of the duration of the predialysis collection period to
      the duration of the interdialytic interval during which the collection was
      accomplished, as well as the urea reduction ratio and predialysis serum urea
      nitrogen concentration of the dialysis session immediately following the end of
      the collection period.

PMID- 27699877
TI  - Laparoendoscopic single-site surgeries: A multicenter experience of 469 cases in
      Japan.
AB  - OBJECTIVE: To report on a multi-institutional series of non-robotic urological
      laparoendoscopic single-site surgery in Japan. METHODS: Consecutive cases of
      laparoendoscopic single-site surgery carried out between February 2009 and
      December 2012 at nine academic institutions were included. We examined the
      surgical outcomes, including conversion and complications rates. RESULTS: Four
      hundred and sixty-nine cases were included in the analysis. The most common
      procedure was adrenalectomy (n = 177) and the second most common procedure was
      radical nephrectomy (n = 143). The procedures also included nephroureterectomy (n
      = 40), living donor nephrectomy (n = 40), pyeloplasty (n = 30), urachal remnant
      excision (n = 9), simple nephrectomy (n = 7), radical prostatectomy (n = 6) and
      others (n = 17). The access sites included umbilicus (n = 248, 53%) and other
      sites (n = 221, 47%). A transperitoneal approach was used in 385 cases (82%), and
      retroperitoneal approach in 84 cases (18%). The median operation time of all
      procedures was 198 min. Conversion to reduced port surgery, conventional
      laparoscopy, or open surgery was noted in 27 cases (5.8%), 12 cases (2.6%), and
      two cases (0.4%), respectively, with an overall conversion rate of 8.7%.
      Intraoperative complications occurred in 10 cases (2.1%). Post-operative
      complications were noted in 29 cases (6.2%), including five major complications
      (1.1%). No mortality was recorded in this series. CONCLUSIONS: Non-robotic
      laparoendoscopic single-site surgery is technically feasible and safe for various
      urologic diseases in Japan. Furthermore, urological laparoendoscopic single-site
      surgery is a promising minimally invasive surgical option that is feasible for
      experienced urological surgeons in intermediate-volume centers as well as high
      volume centers.

PMID- 27699878
TI  - Simulation of Electronic Circular Dichroism of Nucleic Acids: From the Structure
      to the Spectrum.
AB  - We present a quantum mechanical (QM) simulation of the electronic circular
      dichroism (ECD) of nucleic acids (NAs). The simulation combines classical
      molecular dynamics, to obtain the structure and its temperature-dependent
      fluctuations, with a QM excitonic model to determine the ECD. The excitonic model
      takes into account environmental effects through a polarizable embedding and uses
      a refined approach to calculate the electronic couplings in terms of full
      transition densities. Three NAs with either similar conformations but different
      base sequences or similar base sequences but different conformations have been
      investigated and the results were compared with experimental observations; a good
      agreement was seen in all cases. A detailed analysis of the nature of the ECD
      bands in terms of their excitonic composition was also carried out. Finally, a
      comparison between the QM and the DeVoe models clearly revealed the importance of
      including fluctuations of the excitonic parameters and of accurately determining
      the electronic couplings. This study demonstrates the feasibility of the ab
      initio simulation of the ECD spectra of NAs, that is, without the need of
      experimental structural or electronic data.

PMID- 27699879
TI  - 3D in utero quantification of T2* relaxation times in human fetal brain tissues
      for age optimized structural and functional MRI.
AB  - PURPOSE: Maximization of the blood oxygen level-dependent (BOLD) functional MRI
      (fMRI) contrast requires the echo time of the MR sequence to match the T2* value
      of the tissue of interest, which is expected to be higher in the fetal brain
      compared with the brain of a child or an adult. METHODS: T2* values of the
      cortical plate/cortical gray matter tissue in utero in healthy fetuses from mid
      gestation onward (20-36 gestational weeks) were measured using 3D T2* maps
      calculated from 2D dual-echo T2*-weighted data corrected for between-slice motion
      and reconstructed in 1.0 mm3 isotropic resolution from a sequence of multiple
      time points, together with 1.0 mm3 isotropic resolution T2-weighted structural
      data. RESULTS: Mean T2* relaxation times of the cortical tissue were about twice
      as high as those reported previously in adults. In a supporting experiment
      applying single seed analysis, default mode and auditory networks appeared better
      localized and less noisy while using an echo time of 100 ms versus 43 ms. The
      results of the previous study reporting a trend for T2* values to decrease with
      fetal age were reproduced and extended to include cortical tissues and subjects
      in earlier gestation (20-26 gestational weeks). CONCLUSION: The first measurement
      of T2* values in fetal cortical tissues suggested the appropriate echo time range
      for fetal BOLD fMRI protocol optimization to be 130-190 ms. Magn Reson Med 78:909
      916, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine.

PMID- 27699880
TI  - Impact of UVA on pruritus during UVA/B phototherapy of inflammatory skin
      diseases: a randomized double-blind study.
AB  - BACKGROUND: Narrowband (TL-01) UVB phototherapy (UVB nb) is effective in treating
      inflammatory skin disease. The addition of UVA is traditionally advocated to
      reduce pruritus, but lacks evidence for this recommendation. OBJECTIVES: The aim
      of this study was to assess the effect of UVB nb and UVA phototherapy in
      combination compared against UVB nb monotherapy on pruritus, disease activity and
      quality of life. METHODS: In this double-blind randomized clinical trial, 53
      patients suffering from inflammatory skin diseases with pronounced itching
      (Visual Analogue Scale (VAS) for pruritus >=5) were randomized into two treatment
      groups. One group received UVB nb (311 nm) phototherapy alone and another group
      received a combination of UVB nb and UVA (320-400 nm) phototherapy. UV therapy
      was performed three times per week over 16 weeks. Pruritus (VAS and 5-D itch
      score), disease activity and quality of life (Dermatology Life Quality Index,
      DLQI) were assessed at baseline and weeks 4, 8, 12 and 16. RESULTS: In both
      treatment groups, there was a reduction in pruritus scores, disease activity and
      DLQI. No difference in pruritus score, disease activity and quality of life could
      be detected between the group receiving UVB nb alone and those receiving UVB nb
      combined with UVA. CONCLUSIONS: Phototherapy with UVB nb alone, and UVB nb
      combined with UVA are equally effective in treating inflammatory skin disease and
      indifferent in reducing disease-associated pruritus. Given this non-inferiority
      for UVB nb monotherapy, the recommendation of adding UVA to UVB nb phototherapy
      for pruritic inflammatory skin disease should be abandoned.

PMID- 27699882
TI  - What are the Considerations in Balancing Benefits and Risks in Iron Treatment?:
      How Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitors May Change Iron
      Management in End-Stage Renal Disease.

PMID- 27699881
TI  - Structural basis of reversine selectivity in inhibiting Mps1 more potently than
      aurora B kinase.
AB  - Monopolar spindle 1 (Mps1, also known as TTK) is a protein kinase crucial for
      ensuring that cell division progresses to anaphase only after all chromosomes are
      connected to spindle microtubules. Incomplete chromosomal attachment leads to
      abnormal chromosome counts in the daughter cells (aneuploidy), a condition common
      in many solid cancers. Therefore Mps1 is an established target in cancer therapy.
      Mps1 kinase inhibitors include reversine (2-(4-morpholinoanilino)-6
      cyclohexylaminopurine), a promiscuous compound first recognized as an inhibitor
      of the Aurora B mitotic kinase. Here, we present the 3.0-A resolution crystal
      structure of the Mps1 kinase domain bound to reversine. Structural comparison of
      reversine bound to Mps1 and Aurora B, indicates a similar binding pose for the
      purine moiety of reversine making three conserved hydrogen bonds to the protein
      main chain, explaining the observed promiscuity of this inhibitor. The cyclohexyl
      and morpholinoaniline moieties of reversine however, have more extensive contacts
      with the protein in Mps1 than in Aurora B. This is reflected both in structure
      based docking energy calculations, and in new experimental data we present here,
      that both confirm that the affinity of reversine towards Mps1 is about two orders
      of magnitude higher than towards Aurora B. Thus, our data provides detailed
      structural understanding of the existing literature that argues reversine
      inhibits Mps1 more efficiently than Aurora B based on biochemical and in-cell
      assays. Proteins 2016; 84:1761-1766. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699883
TI  - Susceptibility underestimation in a high-susceptibility phantom: Dependence on
      imaging resolution, magnitude contrast, and other parameters.
AB  - PURPOSE: We assessed the accuracy of quantitative susceptibility mapping in a
      gadolinium balloon phantom with a large range of susceptibility values and
      imaging resolutions at 1.5 and 3 Tesla (T). THEORY AND METHODS: The phantom
      contained sources with susceptibility values of 0.4, 0.8, 1.6, and 3.2 ppm and
      was imaged at isotropic resolutions of 0.7, 0.8, 1.2, and 1.8 mm. Numerical
      simulations were performed to match the experimental findings. Voxel sensitivity
      effects were used to explain the susceptibility underestimations. RESULTS: Both
      phantom data and simulation demonstrated that systematic underestimation of the
      susceptibility values increased with voxel size, field strength, and object
      susceptibility. CONCLUSION: The underestimation originates from the signal
      formation in a voxel, which can be described by the voxel sensitivity function.
      The amount of underestimation is thus affected by imaging resolution, magnitude
      contrast, image filtering, and details of the susceptibility inclusions such as
      the susceptibility value and geometry. High-resolution imaging is therefore
      needed for accurate reconstruction of QSM values, especially at higher
      susceptibilities. Magn Reson Med 78:1080-1086, 2017. (c) 2016 International
      Society for Magnetic Resonance in Medicine.

PMID- 27699884
TI  - Solution structure of the Cys74 to Ala74 mutant of the recombinant catalytic
      domain of Zoocin A.
AB  - Zoocin A is a Zn-metallopeptidase secreted by Streptococcus zooepidemicus strain
      4881. Its catalytic domain is responsible for cleaving the D-alanyl-L-alanine
      peptide bond in streptococcal peptidoglycan. The solution NMR structure of the
      Cys74 to Ala74 mutant of the recombinant catalytic domain (rCAT C74A) has been
      determined. With a previous structure determination for the recombinant target
      recognition domain (rTRD), this completes the 3D structure of zoocin A. While the
      structure of rCAT C74A resembles those of the catalytic domains of lysostaphin
      and LytM, the substrate binding groove is wider and no tyrosine residue was
      observed in the active site. Proteins 2016; 85:177-181. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27699885
TI  - Peri-implant soft tissue analyses comparing Ti and ZrO2 abutments: an animal
      study on beagle dogs.
AB  - OBJECTIVE: The aim of this study was to evaluate the soft tissue
      histomorphometric composition around implant abutments comparing two different
      materials, titanium (Ti) and zirconia (ZrO2 ). MATERIAL AND METHODS: Twelve
      implants were placed at bone level in the mandible of six beagle dogs (one in
      each side). At the same day of surgery one titanium abutment was screwed to the
      implant in one side (control group) and a zirconia abutment was screwed in the
      contralateral side. Nine months after implant/abutments placement, animals were
      sacrificed for histological analysis. Descriptive analysis was calculated for
      each variable and Wilcoxon test was applied to evaluate histomorphometric
      variables. RESULTS: At the end of the study the soft tissue dimension at Ti and
      ZrO2 were similar in all counterparts: biological width, the length of the
      barrier epithelium, length of the connective tissue, and the percentage of
      collagen fibers density. However, the percentage of blood vessels was higher for
      the Ti in comparison to ZrO2 (5.11% +/- 1.70 and 2.23% +/- 0.98, respectively [P
      = 0.016]). CONCLUSIONS: Peri-implant soft tissue histomorphology composition was
      similar in implant abutments made of ZrO2 and titanium after 9 months of healing.

PMID- 27699886
TI  - Topical Cidofovir for Recalcitrant Verrucae in Individuals with Severe Combined
      Immunodeficiency After Hematopoietic Stem Cell Transplantation.
AB  - Verrucae vulgaris in patients with severe combined immunodeficiency (SCID) after
      hematopoietic stem cell transplantation (HCST) can be challenging to manage. We
      describe two brothers with X-linked SCID who had severe, persistent verrucae that
      did not respond to traditional topical therapies, including liquid nitrogen,
      imiquimod, salicylic acid, sinecatechins, 40% urea, and 5-fluorourcil. Both
      brothers had full response to topical 3% cidofovir, which should be considered in
      recalcitrant warts in individuals with SCID after HSCT.

PMID- 27699888
TI  - Carbon isotope alteration during the thermal maturation of non-flowering plant
      species representative of those found within the geological record.
AB  - RATIONALE: The carbon isotope (delta13 C value) composition of fossil plant
      material is routinely used as a proxy of past climate and environment change.
      However, palaeoclimate interpretation requires assumptions about the stability of
      delta13 C values in plant material during its decomposition and incorporation
      into sediments. Previous work on modern angiosperm species shows delta13 C
      changes of several per mille during simulated decomposition experiments. However,
      no such tests have been undertaken on non-flowering plants, which are found
      extensively within the geological record. These plants have distinctly different
      cellulose-to-lignin ratios from those of their angiosperm counterparts,
      potentially creating hitherto unknown variations in the original to fossil
      delta13 C signatures. METHODS: To test the extent of delta13 C change during
      decomposition we have subjected a number of plants, representing more basal, non
      flowering plant lineages (cycads, ferns, horsetails and dawn redwood), to
      artificial decay using a hydrothermal maturation technique at two temperatures
      over periods of up to 273 hours. Subsamples were extracted every 12-16 hours and
      analysed for their delta13 C and %C values using a Carlo Erba 1500 elemental
      analyser, and VG TripleTrap and Optima mass spectrometers. RESULTS: The %C values
      increased for all samples through the maturation process at both temperatures
      with the largest increases observed within the first 24 hours. Decreases in
      delta13 C values were observed for all plants at 300 degrees C and for two of the
      species at the lower temperature (200 degrees C). The maximum shift in the
      delta13 C value related to experimental decomposition was -0.900/00 (horsetail),
      indicating a preferential loss of 13 C during thermal maturation. CONCLUSIONS:
      The reduction in the delta13 C value potentially suggests a preferential loss of
      isotopically heavier cellulose in relation to the isotopically lighter lignin
      component during maturation. The isotopic offset observed here (<0.90/00) means
      that palaeoclimatic interpretation of delta13 C values from non-flowering plant
      material within the geological record remains robust, but only where
      interpretations are based on variations in delta13 C values greater than 10/00.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27699887
TI  - Three pairs of weak interactions precisely regulate the G-loop gate of Kir2.1
      channel.
AB  - Kir2.1 (also known as IRK1) plays key roles in regulation of resting membrane
      potential and cell excitability. To achieve its physiological roles, Kir2.1
      performs a series of conformational transition, named as gating. However, the
      structural basis of gating is still obscure. Here, we combined site-directed
      mutation, two-electrode voltage clamp with molecular dynamics simulations and
      determined that H221 regulates the gating process of Kir2.1 by involving a weak
      interaction network. Our data show that the H221R mutant accelerates the rundown
      kinetics and decelerates the reactivation kinetics of Kir2.1. Compared with the
      WT channel, the H221R mutation strengthens the interaction between the CD- and G
      loops (E303-R221) which stabilizes the close state of the G-loop gate and weakens
      the interactions between C-linker and CD-loop (R221-R189) and the adjacent G
      loops (E303-R312) which destabilizes the open state of G-loop gate. Our data
      indicate that the three pairs of interactions (E303-H221, H221-R189 and E303
      R312) precisely regulate the G-loop gate by controlling the conformation of G
      loop. Proteins 2016; 84:1929-1937. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699889
TI  - Reflectance confocal microscopy features of regression in congenital naevus: case
      report.

PMID- 27699890
TI  - The effect of implant macro-thread design on implant stability in the early post
      operative period: a randomized, controlled pilot study.
AB  - INTRODUCTION: Available literature suggests there is a transient drop in implant
      stability from approximately week 0 to week 3-4 as a result of peri-implant bone
      remodeling as it transitions from a primary, mechanical stability to a secondary,
      biological stability. Research investigating the influence of macro-thread design
      on this process is scant. AIM: The specific aim of this study was to evaluate the
      role of macro-thread design on implant stability in the early post-operative
      healing period using resonance frequency analysis (RFA). MATERIAL AND METHODS:
      Seven patients, each missing at least two posterior teeth in the same arch, were
      included in the study. Three patients qualified for four implants resulting in a
      total of 10 matched pairs. All sites were healed (>6 months), non-grafted sites
      with sufficient bone to place implants. Each site in a matched pair was randomly
      assigned to receive either a control (Megagen EZ Plus Internal; EZ) or test
      (Megagen AnyRidge; AR) implant. The test implant incorporates a novel thread
      design with a wide thread depth and increased thread pitch. RFA was used to
      determine implant stability quotient (ISQ) values for each implant at the time of
      placement and weekly for the first 8 weeks. RESULTS: Implants consistently
      achieved a relatively high insertion torque (30-45 N/cm) and high initial ISQ
      value (79.8 +/- 1.49). Baseline ISQ values for test (AR; 79.55 +/- 1.61) and
      control (EZ; 80.05 +/- 1.37) implants were similar. A general pattern of
      stability from baseline through all eight follow-up evaluations was observed for
      the test implants. A pattern of decreasing ISQ values was observed for the
      control implants across the early follow-up evaluations up to week four, where
      the value plateaued. There was a statistically significant main effect due to
      implant type (P < 0.01) and a statistically significant interaction between
      implant type and time (P < 0.01), indicating that the test and control implants
      performed differently at certain time points. CONCLUSIONS: Within the limitations
      of this study, macro-thread design appears to play a role in implant stability in
      the early post-operative healing period as assessed by RFA. These findings may
      have important implications related to immediate or early loading protocols.

PMID- 27699891
TI  - Sweet Structural Signatures Unveiled in Ketohexoses.
AB  - The conformational behaviour of naturally occurring ketohexoses has been revealed
      in a supersonic expansion by Fourier transform microwave spectroscopy coupled
      with a laser ablation source. Three, two and one conformers of d-tagatose, d
      psicose and l-sorbose, respectively, have been identified by their rotational
      constants extracted from the analysis of the spectra. Singular structural
      signatures involving the hydroxyl groups OH(1) and OH(2) have been disentangled
      from the intricate intramolecular hydrogen bond networks stabilising the most
      abundant conformers. The present results place the old Shallenberger and Kier
      sweetness theories on a firmer footing.

PMID- 27699892
TI  - Comprehensive Understanding of Structure-Controlling Factors of a Zinc
      Tetraphenylporphyrin Thin Film Using pMAIRS and GIXD Techniques.
AB  - The performance of an organic electronic device is significantly influenced by
      the anisotropic molecular structure in the film, which has long been difficult to
      predict especially for a solution process. In the present study, a zinc
      tetraphenylporphyrin (ZnTPP) thin film prepared by a solution process was chosen
      to comprehensively explore the molecular-arrangement mechanism as a function of
      representative film-preparation parameters: solvent, film-preparation technique,
      and thermal annealing. The anisotropic structure was first analyzed by using a
      combination of infrared p-polarized multiple-angle incidence resolution
      spectrometry (pMAIRS) and grazing incidence X-ray diffraction (GIXD), which
      readily revealed the molecular orientation and crystal structure, respectively.
      As a result, the real dominant factor was found to be the evaporation time of the
      solvent that determines the initial two different molecular arrangements, types-I
      and -II, while the thermal annealing was found to play an additional role of
      improving the molecular order. The correlation between the molecular orientation
      and the crystal structure was also revealed through the individual orientation
      analysis of the porphyrin and phenyl rings.

PMID- 27699894
TI  - Directional and fluctuating asymmetry among !Kung San and Kavango people of
      Northern Namibia: The impact of sex and subsistence patterns.
AB  - OBJECTIVES: The impact of sex and subsistence on fluctuating and directional
      asymmetry patterns was tested among !Kung San and Kavango people from northern
      Namibia. METHODS: Fluctuating and directional asymmetry from 6 paired traits were
      measured in a sample of 236 !Kung San and 248 Kavango people aged 18 to 65 years
      in the Kavango district and the Nyae-Nyae area of northern Namibia. Signed
      asymmetry, absolute and relative asymmetry, as well as composite fluctuating and
      directional asymmetry, were calculated. RESULTS: Males of both ethnic groups
      exhibited higher fluctuating asymmetry in comparison to their female
      counterparts. Marked differences in directional asymmetry of the upper
      extremities were found between !Kung San and Kavango people. The !Kung San people
      showed a significantly higher directional asymmetry than the Kavango people.
      CONCLUSIONS: Foraging subsistence increased directional asymmetry of the upper
      extremities among males as well as females. In contrast, higher fluctuating
      asymmetry-indicating a higher degree of developmental instability-was found among
      males independent of subsistence group.

PMID- 27699893
TI  - Mapping the interactions of adenoviral E1A proteins with the p160 nuclear
      receptor coactivator binding domain of CBP.
AB  - Many viruses deregulate the cell and force transcription of viral genes by
      competing with cellular proteins for binding to the transcriptional co-activators
      CREB-binding protein (CBP) and p300. Through its interactions with CBP/p300 and
      the retinoblastoma protein, the adenovirus (AdV) early region 1A (E1A)
      oncoprotein hijacks the cell cycle and, in rodents, transforms the cell; the
      mechanistic and structural basis for these effects remain unclear. In this study
      we compare the affinity of protein constructs from the E1A proteins from two
      adenovirus serotypes, non-oncogenic AdV5 and highly oncogenic AdV12, for binding
      to the nuclear receptor coactivator binding domain (NCBD) of CBP. NMR spectra
      show that the E1A constructs from both serotypes are intrinsically disordered in
      the free state and that each contains three homologous binding sites for the
      NCBD, one in the N-terminal region and two within conserved region 1 (CR1) of
      E1A. The binding sites in CR1 correspond to the motifs that bind the
      retinoblastoma protein and the TAZ2 domain of CBP/p300. The E1A and NCBD peptides
      fold synergistically upon complex formation. Binding affinities determined from
      NMR titrations show that, although the overall affinities for AdV5 and AdV12 E1A
      are comparable, there are significant differences between the two E1A serotypes
      in the relative strength with which their constituent interaction motifs bind to
      the NCBD. The individual E1A interaction motifs were unable to compete
      effectively with p53 for binding to the NCBD and both the N-terminal region and
      CR1 region of E1A are required for efficient competition with p53.

PMID- 27699896
TI  - Spotlights on our sister journals: Chem. Eur. J. 42/2016.

PMID- 27699895
TI  - Influence of abutment material on peri-implant soft tissues in anterior areas
      with thin gingival biotype: a multicentric prospective study.
AB  - PURPOSE: The aim of the present clinical trial was to analyze, through
      spectrophotometric digital technology, the influence of the abutment material on
      the color of the peri-implant soft tissue in patients with thin gingival biotype.
      MATERIAL AND METHODS: Thirty-seven patients received an endosseous dental implant
      in the anterior maxilla. At time of each definitive prosthesis delivery, an all
      ceramic crown has been tried on gold, titanium and zirconia abutment. Peri
      implant soft-tissue color has been measured through a spectrophotometer after the
      insertion of each single abutment. Also facial peri-implant soft-tissue thickness
      was measured at the level of the implant neck through a caliper. A specific
      software has been utilized to identify a standardized tissue area and to collect
      the data before the statistical analysis in Lab* color space. DeltaE parameters
      of the selected abutments were tested for correlation with mucosal thickness.
      Pearson correlation test was used. RESULTS: Only 15 patients met the study
      inclusion criteria on peri-implant soft-tissue thickness. Peri-implant soft
      tissue color was different from that around natural teeth, no matter which type
      of restorative material was selected. Measurements regarding all the abutments
      were above the critical threshold of DeltaE 8.74 for intraoral color distinction
      by the naked eye. The DeltaE mean values of gold and zirconium abutments were
      similar (11.43 and 11.37, respectively) and significantly lower (P = 0.03 and P =
      0.04, respectively) than the titanium abutment (13.55). In patients with a facial
      soft-tissue thickness <=2 mm, the DeltaE mean value of gold and zirconia
      abutments was significantly lower than that of titanium abutments (P = 0.03 and P
      = 0.04, respectively) and much more close to the reference threshold of 8.74.
      CONCLUSIONS: For peri-implant soft tissue of <=2 mm, gold or zirconia abutments
      could be selected in anterior areas treatment. Moreover, the thickness of the
      peri-implant soft tissue seemed to be a crucial factor in the abutment impact on
      the color of soft tissues with a thickness of <=2 mm.

PMID- 27699897
TI  - Childhood body mass is positively associated with cesarean birth in Yucatec Maya
      subsistence farmers.
AB  - OBJECTIVE: The epidemiologic link between cesarean birth and childhood obesity is
      unresolved, partly because most studies come from industrialized settings where
      many post-birth factors affect the risk for obesity. We take advantage of an
      unusual ethnographic situation where hospital and cesarean birth modes have
      recently been introduced among Yucatec Maya subsistence farmers, but young
      children have had minimal exposure to the nutritional transition. While we expect
      to find very low rates of childhood obesity, we predict that cesarean-born
      children will be larger and heavier than vaginally born children. METHODS: Weight
      and height were collected monthly on 108 children aged 0-5 (3576 observations
      total). Birth mode and birthweight were collected by maternal interview. Data
      were analyzed using linear mixed models that compare child growth [Maya
      population-specific Z-scores for weight-for-age and body mass index-for-age (WAZ
      and BMIZ)] in cesarean and vaginally born children aged 0-5 years. RESULTS: The
      cesarean rate was 20%, no children were obese, and 5% were overweight. Cesarean
      birth was a significant predictor of child WAZ and BMIZ after accounting for
      maternal effects, child birthweight, and sex. Children who were born by cesarean
      to mothers with high BMI had the highest WAZ of all children by 5 years of age,
      and the highest BMIZ of all children at all ages. CONCLUSION: Cesarean-born Maya
      children had higher BMI than vaginally born children, even in the absence of many
      known confounding factors that contribute to childhood obesity. Child growth was
      most sensitive to birth mode when mothers had high BMI.

PMID- 27699899
TI  - An Anionic Interpenetrated Zeolite-Like Metal-Organic Framework Composite As a
      Tunable Dual-Emission Luminescent Switch for Detecting Volatile Organic
      Molecules.
AB  - The luminescent MOF [(CH3 )2 NH2 ]2 [(Zn2 O)L]?5 DMF (NENU-519, NENU=Northeast
      Normal University) with a zeolite BCT topology was successfully synthesized. It
      is a rare example of a two-fold interpenetrated framework with a zeolite
      topology. NENU-519 demonstrates the ability to selectively adsorb cationic dyes.
      Furthermore we developed Rh6@NENU-519 (Rh6=Rhodamine 6G) as a dual-emitting
      sensor for probing different volatile organic molecules (VOMs) due to an energy
      transfer between L and the dye. The composite can be used to distinguish the
      isomers of o-, m-, and p-xylene and ethylbenzene using the emission-peak-height
      ratios of L to the dye as detectable signals, in which the readout signals are
      involved in the interactions between the dye@MOF composite and the guest
      analytes. Moreover, Rh6@NENU-519 can serve as a luminescent switch for the
      detection of different aromatic compounds, like benzene, benzene substituted with
      different groups, and pyridine. In other words, the Rh6@NENU-519 composite can be
      used as molecular decoder of the structural information of different VOMs into
      recognizable luminescent signals. Hopefully this work will open a new corridor to
      develop luminescent guest@MOF composites as sensors for practical applications.

PMID- 27699898
TI  - Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo
      lipogenesis and novel lipids.
AB  - Obesity, the major cause of the current global epidemic of type 2 diabetes (T2D),
      induces insulin resistance in peripheral insulin target tissues. Several
      mechanisms have been identified related to cross-talk between adipose tissue,
      skeletal muscle and liver. These mechanisms involve both increased free fatty
      acid release and altered secretion of adipokines from adipose tissue. A major
      determinant of metabolic health is the ability of subcutaneous adipose tissue
      (SAT) to store excess fat rather than allowing it to accumulate in ectopic depots
      including liver (i.e. in nonalcoholic fatty liver disease), muscle and heart, or
      in epicardial/pericardial and visceral fat depots which promote the metabolic
      complications of obesity. The ability to recruit and differentiate precursor
      cells into adipose cells (adipogenesis) in SAT is under genetic regulation and is
      reduced in high-risk individuals who have first-degree relatives with T2D. Early
      recruitment of new adipose cells is dependent on the cross-talk between canonical
      WNT and BMP4 signalling; WNT enhances their undifferentiated and proliferative
      state whereas BMP4 induces their commitment to the adipogenic lineage.
      Dysregulation of these signalling pathways is associated with impaired
      adipogenesis and impaired ability to respond to the need to store excess lipids
      in SAT. This leads to hypertrophic, dysfunctional and insulin-resistant adipose
      cells with a reduced content of GLUT4, the major insulin-regulated glucose
      transporter, which in turn reduces adipose tissue glucose uptake and de novo
      lipogenesis. We recently identified that reduced GLUT4 and lipogenesis in
      adipocytes impairs the synthesis of a novel family of lipids secreted by adipose
      tissue (and potentially other tissues), branched fatty acid esters of hydroxy
      fatty acids (FAHFAs). FAHFAs have beneficial metabolic effects, including
      enhancing insulin-stimulated glucose transport and glucose-stimulated GLP1 and
      insulin secretion, as well as powerful anti-inflammatory effects. FAHFA levels
      are reduced in subcutaneous adipose tissue in insulin-resistant individuals, and
      this novel family of lipids may become of future therapeutic use.

PMID- 27699900
TI  - Pretreatment with beta-adrenergic receptor agonists facilitates induction of LTP
      and sharp wave ripple complexes in rodent hippocampus.
AB  - Norepinephrine, is involved in the enhancement of learning and memory formation
      by regulating synaptic mechanisms through its ability to activate pre- and post
      synaptic adrenergic receptors. Here we show that beta-agonists of norepinephrine
      facilitate the induction of both associational LTP and sharp wave ripples (SPW
      Rs) in acute slices of rat hippocampus in area CA3. Surprisingly, this
      facilitating effect persists when slices are only pretreated with beta-receptor
      agonists followed by wash out and application of the unspecific beta
      adrenoreceptor (betaAR) antagonist propranolol. During application of betaAR
      agonists repeated stimulation resulted in facilitated induction of SPW-Rs. Since
      SPW-Rs are thought to be involved in memory replay we studied the effects of
      betaAR-agonists on spontaneous SPW-Rs in murine hippocampus and found that
      amplitude and incidence of SPW-Rs increased. These effects involve cyclic-AMP and
      the activation of protein kinase A and suggest a supportive role in memory
      consolidation. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699901
TI  - Model of the delayed translation of cyclin B maternal mRNA after sea urchin
      fertilization.
AB  - Sea urchin eggs exhibit a cap-dependent increase in protein synthesis within
      minutes after fertilization. This rise in protein synthesis occurs at a constant
      rate for a great number of proteins translated from the different available
      mRNAs. Surprisingly, we found that cyclin B, a major cell-cycle regulator,
      follows a synthesis pattern that is distinct from the global protein population,
      so we developed a mathematical model to analyze this dissimilarity in
      biosynthesis kinetic patterns. The model includes two pathways for cyclin B mRNA
      entry into the translational machinery: one from immediately available mRNA
      (mRNAcyclinB) and one from mRNA activated solely after fertilization
      (XXmRNAcyclinB). Two coefficients, alpha and beta, were added to fit the measured
      scales of global protein and cyclin B synthesis, respectively. The model was
      simplified to identify the synthesis parameters and to allow its simulation. The
      calculated parameters for activation of the specific cyclin B synthesis pathway
      after fertilization included a kinetic constant (ka ) of 0.024 sec-1 , for the
      activation of XXmRNAcyclinB, and a critical time interval (t2 ) of 42 min. The
      proportion of XXmRNAcyclinB form was also calculated to be largely dominant over
      the mRNAcyclinB form. Regulation of cyclin B biosynthesis is an example of a
      select protein whose translation is controlled by pathways that are distinct from
      housekeeping proteins, even though both involve the same cap-dependent initiation
      pathway. Therefore, this model should help provide insight to the signaling
      utilized for the biosynthesis of cyclin B and other select proteins. Mol. Reprod.
      Dev. 83: 1070-1082, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699903
TI  - Redox-Active M8 L6 Cubic Hosts with Tetraphenylethylene Faces Encapsulate Organic
      Dyes for Light-Driven H2 Production.
AB  - The design of artificial systems that mimic highly evolved and finely tuned
      natural enzymes is a promising subject of intensive research. The assembly of O
      symmetric cubic structures with an Fe8 L6 formula was reported through the direct
      combination of a C4 -symmetric tetraphenylethylene-based ligand with a C3 
      symmetric tris(bipyridine)iron node. The robust metal-organic cubes are rich in
      pi-electron density and provide favorable interactions with planar polycyclic
      aromatic hydrocarbons. Within the confined space of the host, the aromatic
      hydrocarbons molecules are forced closer to the redox active host, and the
      photoinduced electron transfer (PET) is modified into a pseudo-intramolecular
      pathway. These iron vertices within the cubes exhibit suitable redox potential
      for electrochemical reduction of protons and the well-modified PET is further
      tailored to create artificial systems for light-driven hydrogen evolution from
      water through the encapsulation of fluorescein dyes. Control experiments based on
      a mononuclear compound resembling the iron corner of the octahedron suggest an
      enzymatic dynamic behavior. The new, well-elucidated reaction pathways and the
      increased molarity of the reaction within the confined space render these
      supramolecular systems superior to other relevant systems.

PMID- 27699902
TI  - Integrin alpha11 is overexpressed by tumour stroma of head and neck squamous cell
      carcinoma and correlates positively with alpha smooth muscle actin expression.
AB  - BACKGROUND: Cancer-associated fibroblasts (CAFs) were shown to be important for
      tumour progression in head and neck squamous cell carcinomas (HNSCCs). Their
      heterogeneity and lack of specific markers is increasingly recognized. Integrin
      alpha11 was recently shown to be expressed by CAFs and might serve as a specific
      CAF marker. AIM: To investigate integrin alpha11 expression and its correlation
      with the expression of a well-known marker of CAF, alpha smooth muscle actin
      (alpha-SMA), in HNSCC. METHODS: Fresh frozen (FF) and formalin-fixed paraffin
      embedded (FFPE) samples from healthy volunteers (n = 24), oral lichen planus
      (OLP) (n = 32) and HNSCC (n = 106) were collected together with clinical data
      after ethical approval. Immunohistochemistry to detect integrin alpha11 and alpha
      SMA was performed on FF and FFPE samples. qPCR for integrin alpha11 (ITGA11) and
      alpha-SMA (ACTA2) was performed on FF samples. Data were analysed using chi
      square test and Kaplan-Meier survival analysis. RESULTS: Significantly higher
      levels of integrin alpha11 and alpha-SMA at both protein and mRNA levels were
      found in HNSCC vs. normal controls and OLP. A strong correlation was found
      between integrin alpha11 and alpha-SMA expression, and double staining showed
      their colocalization. Both integrin alpha11 and alpha-SMA were detected
      surrounding metastatic islands. Expression of alpha-SMA at tumour front but not
      tumour centre correlated with patient survival. CONCLUSION: Integrin alpha11 was
      overexpressed in HNSCC stroma and colocalized with alpha-SMA. Expression of alpha
      SMA at tumour front but not tumour centre had prognostic value for survival,
      pinpointing the importance of assessing tumour front when evaluating stromal
      molecules as prognostic biomarkers.

PMID- 27699904
TI  - Rational Control of Conformational Distributions and Mixed-Valence
      Characteristics in Diruthenium Complexes.
AB  - The electronic characteristics of mixed-valence complexes are often inferred from
      the shape of the inter-valence charge transfer (IVCT) band, which usually falls
      in the near infrared (NIR) region, and relationships derived from Marcus-Hush
      theory. These analyses typically assume one single, dominant molecular
      conformation. The NIR spectra of the prototypical delocalised (Class III Robin
      Day mixed-valence) complexes [{Ru(pp)Cp'}2 (MU-C=C-C=C)]+ ([1]+ : Cp'=Cp,
      pp=(PPh3 )2 ; [2]+ : Cp'=Cp, pp=dppe; [3]+ : Cp'=Cp*, pp=dppe) feature a 'two
      band' pattern, which complicates band-shape analysis using these traditional
      methods. In the past, the appearance of sub-bands within or near the IVCT
      transition has been attributed to vibronic effects or localised d-d transitions.
      Quantum-chemical modelling of a series of rotational conformers of [1]+ -[3]+
      reveals the two components that contribute to the NIR absorption band envelope to
      be a pi-pi* transition and an MLCT transition. The MLCT components only gain
      appreciable intensity when the orientation of the half-sandwich ruthenium ligand
      spheres deviates from idealised cis (Omega P-Ru-Ru-P=0 degrees ) or trans (Omega
      P-Ru-Ru-P=180 degrees ) conformations. The increased steric demand of the
      supporting ligands, together with some underlying inter-phosphine ligand T-shaped
      CH???pi stacking interactions across the series [1]+ to [2]+ to [3]+ results in
      local minima biased towards such non-idealised conformations of the metal-ligand
      fragments (Omega P-Ru-Ru-P=33-153 degrees ). Experimentally, this is indicated by
      appearance of multiple bands within the IR nu~ (C=C) band envelopes and
      increasing intensity of the higher-energy MLCT transition(s) relative to the pi
      pi* transition across the series, and the appearance of a pronounced 'two-band'
      pattern in the experimental NIR absorption envelopes. These conformational
      effects and the methods of analysis presented here, which combine analysis of IR
      and NIR spectra with quantum-chemical calculations on a range of energetically
      similar conformational minima, are expected to be quite general for mixed-valence
      systems.

PMID- 27699905
TI  - Freezing the Dynamic Gap for Selectivity: Motion-Based Design of Inhibitors of
      the Shikimate Kinase Enzyme.
AB  - Shikimate kinase (SK), the fifth enzyme of the aromatic amino acid biosynthesis,
      is a recognized target for antibiotic drug discovery. The potential of the
      distinct dynamic apolar gap, which isolates the natural substrate from the
      solvent environment for catalysis, and the motion of Mycobacterium tuberculosis
      and Helicobacter pylori SK enzymes, which was observed by molecular dynamics
      simulations, was explored for inhibition selectivity. The results of the
      biochemical and computational studies reveal that the incorporation of bulky
      groups at position C5 of 5-aminoshikimic acid and the natural substrate enhances
      the selectivity for the H. pylori enzyme due to key motion differences in the
      shikimic acid binding domain (mainly helix alpha5). These studies show that the
      less-exploited motion-based design approach not only is an alternative strategy
      for the development of competitive inhibitors, but could also be a way to achieve
      selectivity against a particular enzyme among its homologues.

PMID- 27699907
TI  - Access to alpha-Arylglycines by Umpolung Carboxylation of Aromatic Imines with
      Carbon Dioxide.
AB  - A straightforward and transition-metal-free approach for the efficient synthesis
      of alpha-arylglycine derivatives from aromatic imines and carbon dioxide was
      enabled by an umpolung carboxylation reaction. Various substituted
      diphenylmethimines underwent the carboxylation smoothly with carbon dioxide in
      the presence of potassium tert-butoxide and 18-crown-6 to give the corresponding
      carboxylated products in good to high yields. Besides the enhancement of the
      solubility of potassium tert-butoxide in THF, 18-crown-6 also plays key roles in
      suppressing the reverse protonation or 1, 3-proton shift isomerization as well as
      by stabilizing the carboxylated intermediate.

PMID- 27699906
TI  - Stable isotope analyses of oxygen (18 O:17 O:16 O) and chlorine (37 Cl:35 Cl) in
      perchlorate: reference materials, calibrations, methods, and interferences.
AB  - RATIONALE: Perchlorate (ClO4- ) is a common trace constituent of water, soils,
      and plants; it has both natural and synthetic sources and is subject to
      biodegradation. The stable isotope ratios of Cl and O provide three independent
      quantities for ClO4- source attribution and natural attenuation studies: delta37
      Cl, delta18 O, and delta17 O (or Delta17 O or 17 Delta) values. Documented
      reference materials, calibration schemes, methods, and interferences will improve
      the reliability of such studies. METHODS: Three large batches of KClO4 with
      contrasting isotopic compositions were synthesized and analyzed against VSMOW
      SLAP, atmospheric O2 , and international nitrate and chloride reference
      materials. Three analytical methods were tested for O isotopes: conversion of
      ClO4- to CO for continuous-flow IRMS (CO-CFIRMS), decomposition to O2 for dual
      inlet IRMS (O2-DIIRMS), and decomposition to O2 with molecular-sieve trap (O2
      DIIRMS+T). For Cl isotopes, KCl produced by thermal decomposition of KClO4 was
      reprecipitated as AgCl and converted into CH3 Cl for DIIRMS. RESULTS: KClO4
      isotopic reference materials (USGS37, USGS38, USGS39) represent a wide range of
      Cl and O isotopic compositions, including non-mass-dependent O isotopic
      variation. Isotopic fractionation and exchange can affect O isotope analyses of
      ClO4- depending on the decomposition method. Routine analyses can be adjusted for
      such effects by normalization, using reference materials prepared and analyzed as
      samples. Analytical errors caused by SO42- , NO3- , ReO42- , and C-bearing
      contaminants include isotope mixing and fractionation effects on CO and O2 , plus
      direct interference from CO2 in the mass spectrometer. The results highlight the
      importance of effective purification of ClO4- from environmental samples.
      CONCLUSIONS: KClO4 reference materials are available for testing methods and
      calibrating isotopic data for ClO4- and other substances with widely varying Cl
      or O isotopic compositions. Current ClO4- extraction, purification, and analysis
      techniques provide relative isotope-ratio measurements with uncertainties much
      smaller than the range of values in environmental ClO4- , permitting isotopic
      evaluation of environmental ClO4- sources and natural attenuation. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27699908
TI  - Oncologists' communication about end of life: the relationship among secondary
      traumatic stress, compassion satisfaction, and approach and avoidance
      communication.
AB  - BACKGROUND: Oncologists must communicate effectively with patients and their
      families about end of life (EOL). Despite the importance of communicating on this
      topic, many oncologists avoid these conversations. The objective of this study
      was to examine the associations between secondary traumatic stress and compassion
      satisfaction and approach and avoidant communication about EOL with cancer
      patients. METHODS: A convenience sample of 79 oncologists (n = 27 men, n = 52
      women) participated in the study. Oncologists completed a survey that included a
      sociodemographic and clinical information questionnaire, the Professional Quality
      of Life Scale, and Communication about End of Life Survey. To examine the effect
      of secondary traumatic stress and compassion satisfaction on approach and
      avoidant communication, while controlling for gender and age, 2 hierarchical
      linear regression analyses were computed. RESULTS: Oncologists reported high
      levels of secondary traumatic stress and high compassion satisfaction. Scores on
      the approach and avoidant communication scales were in the mid-range of the
      scale. Lower reports of secondary traumatic stress and higher compassion
      satisfaction were associated with higher approach communication strategies:
      however, only higher secondary traumatic stress was associated with higher
      avoidant communication strategies. CONCLUSIONS: Our findings indicate that there
      is an association between emotional factors and approach communication. The
      findings have clinical implications in designing effective communication skills
      training. Further research and training should take secondary traumatic stress
      and compassion satisfaction into consideration to be able to ensure that terminal
      patients and their families receive the best quality EOL care.

PMID- 27699909
TI  - Rapid detection of alteration of serum IgG in patients with schizophrenia after
      risperidone treatment by matrix-assisted laser desorption ionization/time-of
      flight mass spectrometry.
AB  - RATIONALE: The aim of the study was to use a technique that combines acid
      hydrolysis and matrix-assisted laser desorption ionization/time-of-flight mass
      spectrometry (MALDI-TOF MS) in order to detect the serum biomarkers of patients
      diagnosed with schizophrenia both before and after four-week antipsychotic
      treatment with risperidone. METHODS: During this study's two-year period,
      inpatients were diagnosed with schizophrenia using the Structured Clinical
      Interview for DSM-IV Axis I Disorders. Severity was then evaluated using the
      Positive and Negative Syndrome Scale both at baseline and at endpoint following
      four-week treatment with risperidone. The patients' serum biomarkers were quickly
      measured using acid hydrolysis and MALDI-TOF MS. The resulting peptides were then
      analyzed using MALDI-TOF MS. We constructed a receiver operating characteristic
      (ROC) curve for the evaluated biomarkers. RESULTS: We recruited 20 pairs of
      participants for this study. The experimental group was treated with serum
      protein with HCl for 10 minutes to effectively hydrolyze abundant proteins. The
      target peptide, the immunoglobulin gamma chain (IgG), was then rapidly detected
      using this manner. A significant difference was found in the IgG levels of
      patients with schizophrenia before and after antipsychotic treatment. We
      constructed a ROC curve based on the IgG, and the area under said curve was
      0.969. In comparison to conventional detection protocols, this method takes only
      minutes to complete and is also less costly. CONCLUSIONS: This study found that
      applying acid hydrolysis with MALDI-TOF MS technology could rapidly differentiate
      serum IgG levels in patients with schizophrenia before and after being treated
      with risperidone. This IgG difference may enhance the understanding of mechanism
      of antipsychotic treatment of schizophrenia. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27699910
TI  - POSITRON EMISSION TOMOGRAPHY OF THE EQUINE DISTAL LIMB: EXPLORATORY STUDY.
AB  - Positron emission tomography (PET) is a highly sensitive, noninvasive imaging
      technique for quantifying biological functions of tissues. However, at the time
      of this study, PET imaging applications had not been reported in the horse. The
      aim of this exploratory study was to determine whether a portable high-resolution
      PET scanner could be used to image the equine distal limb. Images of the front
      feet and fetlocks of three research horses, with known lesions localized to the
      distal front limbs, were acquired under general anesthesia after administration
      of 18 F-fluorodeoxyglucose (18 F-FDG), with doses ranging from 1.5 to 2.9 MBq/kg.
      The radiation exposure measured during imaging was slightly higher than 99m
      Technetium scintigraphy. However, the use of general anesthesia allowed the
      proximity and the contact time with the patient to be minimized for the staff
      involved. 18 F-FDG uptake was evident throughout the soft tissues, with the
      highest uptake in the coronary band and the lowest uptake in the tendons.
      Anatomic structures could be discriminated due to the high contrast between soft
      tissue and bone. Detected lesions included lysis of the flexor cortex of the
      navicular bone, lesions of flexor tendons and suspensory ligament, and abnormal
      uptake through the lamina of a laminitic subject. Findings indicated that
      tomographic molecular imaging is feasible in the equine distal limb and could be
      useful as a future diagnostic technique for clinical and research studies,
      especially those involving tendinopathy/desmopathy and laminitis.

PMID- 27699911
TI  - Individual prediction of long-term outcome in adolescents at ultra-high risk for
      psychosis: Applying machine learning techniques to brain imaging data.
AB  - An important focus of studies of individuals at ultra-high risk (UHR) for
      psychosis has been to identify biomarkers to predict which individuals will
      transition to psychosis. However, the majority of individuals will prove to be
      resilient and go on to experience remission of their symptoms and function well.
      The aim of this study was to investigate the possibility of using structural MRI
      measures collected in UHR adolescents at baseline to quantitatively predict their
      long-term clinical outcome and level of functioning. We included 64 UHR
      individuals and 62 typically developing adolescents (12-18 years old at
      recruitment). At six-year follow-up, we determined resilience for 43 UHR
      individuals. Support Vector Regression analyses were performed to predict long
      term functional and clinical outcome from baseline MRI measures on a continuous
      scale, instead of the more typical binary classification. This led to predictive
      correlations of baseline MR measures with level of functioning, and negative and
      disorganization symptoms. The highest correlation (r = 0.42) was found between
      baseline subcortical volumes and long-term level of functioning. In conclusion,
      our results show that structural MRI data can be used to quantitatively predict
      long-term functional and clinical outcome in UHR individuals with medium effect
      size, suggesting that there may be scope for predicting outcome at the individual
      level. Moreover, we recommend classifying individual outcome on a continuous
      scale, enabling the assessment of different functional and clinical scales
      separately without the need to set a threshold. Hum Brain Mapp 38:704-714, 2017.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27699913
TI  - Effect of intracanal cryotherapy on pain after single-visit root canal treatment.
AB  - The purpose of this study was to evaluate the effect of 2.5 degrees C cold saline
      irrigation as final irrigant on postoperative pain after single-visit root canal
      treatment of teeth with vital pulps. One-hundred and seventy patients were
      assessed as eligible and included to the study. The teeth were randomly divided
      into two groups (n = 85) (i.e. the control group and the cryotherapy group). In
      the cryotherapy group, final irrigation with 2.5 degrees C 0.9% physiological
      saline solution for 5 min was performed following completion of biomechanical
      preparation, whereas in control group same solution stored at the root
      temperature was used. Treatments were performed in a single visit. Participants
      were asked to rate the intensity of their postoperative pain using visual
      analogue scale at 24 and 48 h. Data were analysed by Mann-Whitney U test and
      Student's t test. In the cryotherapy group level of reported postoperative pain
      was significantly lower than the control group (P < 0.05, Mann-Whitney U test).
      The outcome of this investigation indicates that 2.5 degrees C cold saline
      irrigation as final irrigant can result a significant reduction in postoperative
      pain levels in comparison to the control group. Cryotherapy is a simple, cost
      effective, and non-toxic option for postoperative pain control in single visit
      root canal treatment.

PMID- 27699912
TI  - PROTECTED-UK - Clinical pharmacist interventions in the UK critical care unit:
      exploration of relationship between intervention, service characteristics and
      experience level.
AB  - PURPOSE: Clinical pharmacist (CP) interventions from the PROTECTED-UK cohort, a
      multi-site critical care interventions study, were further analysed to assess
      effects of: time on critical care, number of interventions, CP expertise and days
      of week, on impact of intervention and ultimately contribution to patient care.
      METHODS: Intervention data were collected from 21 adult critical care units over
      14 days. Interventions could be error, optimisation or consults, and were blind
      coded to ensure consistency, prior to bivariate analysis. Pharmacy service
      demographics were further collated by investigator survey. KEY FINDINGS: Of the
      20 758 prescriptions reviewed, 3375 interventions were made (intervention rate
      16.1%). CPs spent 3.5 h per day (mean, +/-SD 1.7) on direct patient care,
      reviewed 10.3 patients per day (+/-SD 4.2) and required 22.5 min (+/-SD 9.5) per
      review. Intervention rate had a moderate inverse correlation with the time the
      pharmacist spent on critical care (P = 0.05; r = 0.4). Optimisation rate had a
      strong inverse association with total number of prescriptions reviewed per day (P
      = 0.001; r = 0.7). A consultant CP had a moderate inverse correlation with number
      of errors identified (P = 0.008; r = 0.6). No correlation existed between the
      presence of electronic prescribing in critical care and any intervention rate.
      Few centres provided weekend services, although the intervention rate was
      significantly higher on weekends than weekdays. CONCLUSIONS: A CP is essential
      for safe and optimised patient medication therapy; an extended and developed
      pharmacy service is expected to reduce errors. CP services should be adequately
      staffed to enable adequate time for prescription review and maximal therapy
      optimisation.

PMID- 27699914
TI  - Oxime ligation in acetic acid: efficient synthesis of aminooxy-peptide
      conjugates.
AB  - Oxime ligation is a powerful tool in various bioconjugation strategies.
      Nevertheless, high reaction rates and quantitative yields are typically reported
      for aldehyde-derived compounds. In contrary, keto groups react much slower, with
      quantitative yields achieved at 5 h for low-molecular weight compounds and more
      than 15 h for polymers or dendrimers. In this communication, we report that oxime
      ligation proceeds rapidly with quantitative (>95%) conversion within 1.5-2 h in
      pure acetic acid. The practical utility of suggested technique is illustrated by
      the synthesis of peptide-steroid and peptide-polymer conjugates of model aminooxy
      peptides. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd.

PMID- 27699915
TI  - Relationship between physical performance and quality of life in Charcot-Marie
      Tooth disease: a pilot study.
AB  - Charcot-Marie-Tooth (CMT) is a rare inherited peripheral neuropathy in which
      quality of life (QoL) is reduced compared with the general population. This paper
      investigates the relationship between QoL and physical performance in people with
      CMT with the aim of identifying avenues for future research into rehabilitation
      strategies. Cross-sectional data was obtained from 10 participants (5 men, 5
      women, age 46 +/- 13 years, height 1.7 +/- 0.1 m, body mass 77 +/- 17 kg) with
      CMT (CMT1A n = 5; CMT-X n = 3; unknown genetic origin n = 2). Participants were
      evaluated for QoL, falls efficacy (FES), balance, mobility, muscle strength, and
      power. Physical component score (PCS) of the Short Form-36 (SF-36) was
      significantly and directly related to higher leg press power (r = 0.75, p =
      0.02). Better FES scores were significantly related to faster habitual gait speed
      (r = -0.70, p = 0.02), left hip abduction, and seated row strength (r = -0.68, p
      = 0.03; r = -0.73, p = 0.03, respectively). Future research should aim to
      substantiate these preliminary findings in a larger cohort and investigate
      whether interventions targeting muscle strength and power can improve QoL and
      mobility outcomes in people with CMT.

PMID- 27699917
TI  - Bulk delta15 N measurements of organic-rich rock samples by elemental
      analyzer/isotope ratio mass spectrometry with enhanced oxidation ability.
AB  - RATIONALE: Elemental analyzer/isotope ratio mass spectrometry (EA/IRMS) has been
      widely used for nitrogen isotope ratio determination in various organic and
      inorganic samples. However, the extent of the redox reaction in the EA reaction
      tube can greatly affect the accuracy and precision of measurements, especially in
      the case of complex geological samples. It is therefore necessary to determine
      the appropriate reaction conditions to reach a high recovery of nitrogen by
      complete combustion or thermal decomposition and quantitative reduction. METHODS:
      The conventional Dumas dual-inlet method was used to determine the bulk nitrogen
      isotope composition of SGR-1 (an organic-rich standard sample), which then was
      analyzed by EA/IRMS under different EA reaction conditions to study the influence
      of the redox environment on the delta15 N measurements. The measured data
      together with the results reported by previous researchers were used to evaluate
      the effectiveness of the nitrogen extraction for organic-rich rock samples.
      RESULTS: Our results demonstrated that with the Dumas dual-inlet method more
      oxidizing agent (CuO) addition to SGR-1 would yield a higher nitrogen content of
      0.91% than the recommended content (0.81%) although a delta15 N value of 17.39 +/
      0.090/00 was consistent with the recommended value by USGS. Using EA/IRMS, when
      more O2 was injected in the reaction tube, a high nitrogen content (0.92 +/-
      0.01%) and a delta15 N value (17.43 +/- 0.170/00) close to that of the Dumas dual
      inlet method were obtained. The addition of V2 O5 or CuO in a continuous-flow
      system of EA/IRMS could not effectively enable the complete combustion of SGR-1.
      CONCLUSIONS: When measuring the nitrogen isotope composition of organic-rich rock
      sample dominated by reduced substances with EA/IRMS, greater O2 injection will
      enable more complete combustion to obtain reliable nitrogen yields compared with
      the addition of V2 O5 or CuO. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27699916
TI  - Design of peptidase-resistant peptide inhibitors of myosin light chain kinase.
AB  - Myosin light chain kinase (MLCK) is a key regulator of various forms of cell
      motility including smooth muscle contraction, cell migration, cytokinesis,
      receptor capping, secretion, etc. Inhibition of MLCK activity in endothelial and
      epithelial monolayers using cell-permeant peptide Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg
      Lys (PIK, Peptide Inhibitor of Kinase) allows protecting the barrier capacity,
      suggesting a potential medical use of PIK. However, low stability of L-PIK in a
      biological milieu prompts for development of more stable L-PIK analogues for use
      as experimental tools in basic and drug-oriented biomedical research. Previously,
      we designed PIK1, H-(Nalpha Me)Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2 , that was
      2.5-fold more resistant to peptidases in human plasma in vitro than L-PIK and
      equal to it as MLCK inhibitor. In order to further enhance proteolytic stability
      of PIK inhibitor, we designed the set of six site-protected peptides based on L
      PIK and PIK1 degradation patterns in human plasma as revealed by 1 H-NMR
      analysis. Implemented modifications increased half-live of the PIK-related
      peptides in plasma about 10-fold, and these compounds retained 25-100% of L-PIK
      inhibitory activity toward MLCK in vitro. Based on stability and functional
      activity ranking, PIK2, H-(Nalpha Me)Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-D-Arg-Lys-NH2 ,
      was identified as the most stable and effective L-PIK analogue. PIK2 was able to
      decrease myosin light chain phosphorylation in endothelial cells stimulated with
      thrombin, and this effect correlated with the inhibition by PIK2 of thrombin
      induced endothelial hyperpermeability in vitro. Therefore, PIK2 could be used as
      novel alternative to other cell-permeant inhibitors of MLCK in cell culture-based
      and in vivo studies where MLCK catalytic activity inhibition is required.
      Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd.

PMID- 27699918
TI  - Novel 3-D cell culture system for in vitro evaluation of anticancer drugs under
      anchorage-independent conditions.
AB  - Anticancer drug discovery efforts have used 2-D cell-based assay models, which
      fail to forecast in vivo efficacy and result in a lower success rate of clinical
      approval. Recent 3-D cell culture models are expected to bridge the gap between 2
      D and in vivo models. However, 3-D cell culture methods that are available for
      practical anticancer drug screening have not yet been fully attained. In this
      study, we screened several polymers for their ability to suspend cells or cell
      spheroids homogeneously in a liquid medium without changing the viscosity
      behavior, and identified gellan gum (FP001), as the most potent polymer. FP001
      promoted cell dispersion in the medium and improved the proliferation of a wide
      range of cancer cell lines under low attachment conditions by inhibiting the
      formation of large-sized spheroids. In addition, cancer cells cultured with FP001
      containing medium were more susceptible to inhibitors of epidermal growth factor
      (EGF) signaling than those cultured under attachment conditions. We also showed
      that ligands of the EGF receptor family clearly enhance proliferation of SKOV3
      ovarian carcinoma cells under anchorage-independent conditions with FP001.
      Consistent with this result, the cells grown with FP001 showed higher EGF
      receptor content compared with cells cultured under attachment conditions. In
      conclusion, we developed a novel 3-D cell culture system that is available for
      high throughput screening of anticancer agents, and is suitable for evaluation of
      molecular-targeted anticancer drugs. Three-dimensional cell culture using FP001
      will be of value in the development of useful technologies for anticancer drug
      discovery.

PMID- 27699919
TI  - Obstructive sleep apnoea pathogenesis from mild to severe: Is it all the same?
AB  - Obstructive sleep apnoea (OSA) is a common disorder caused by not only an
      impaired upper airway anatomy (i.e. anatomically narrow/collapsible airway), but
      also by several non-anatomical factors. In this review, we summarise what is
      known about how each of the pathological factors that cause OSA vary according to
      disease severity as measured by the apnoea-hypopnoea index. Our synthesis of the
      available literature indicates that most of the key factors that cause OSA vary
      with disease severity. However, there is substantial heterogeneity such that the
      relative contribution of each of these traits varies both between patients and
      within different severities of disease. These differences likely contribute to
      variable efficacy of many non-continuous positive airway pressure treatments and
      inconsistencies in responses with regard to different OSA severities at baseline.

PMID- 27699920
TI  - Change Factors in the Process of Cognitive-Behavioural Therapy for Obsessive
      Compulsive Disorder.
AB  - : While there is a plethora of evidence for the efficacy of cognitive-behavioural
      therapy (CBT) in obsessive-compulsive disorder (OCD), studies on change factors
      of the therapeutic process that account for this success are scarce. In the
      present study, 155 participants with primary OCD were investigated during CBT
      inpatient treatment. The Yale-Brown Obsessive-Compulsive Scale-SR served as a
      measure of symptom severity. In addition, the following process change factors
      were measured: therapeutic relationship, experience of self-esteem during
      therapy, experience of mastery, problem actualization and clarification. All
      variables were assessed on a weekly basis for seven weeks. Linear mixed growth
      curve analyses were conducted to model the decrease of symptoms over time and to
      analyse whether the change factors predicted symptom reduction. The analyses
      revealed a linear decrease of symptoms with high inter-individual variation.
      Results further showed that increase in self-esteem and mastery experiences as
      well as the initial score on mastery experience and clarification predicted
      decrease on the Y-BOCS. We conclude that CBT therapists should focus on
      clarification in the very first sessions, and try to boost self-esteem and self
      efficacy, which is related to mastery, throughout the treatment of OCD. Copyright
      (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Increase in mastery
      and self-esteem experiences are associated with symptom decrease in obsessive
      compulsive disorder (OCD) during cognitive-behavioural therapy (CBT). Initial
      score of mastery experiences and problem clarification predict symptom decrease
      in OCD during CBT. CBT therapists should focus on problem clarification in the
      very first sessions and try to boost self-esteem and self-efficacy throughout the
      treatment of OCD.

PMID- 27699921
TI  - COMPUTED TOMOGRAPHIC FINDINGS IN CANINE ELBOWS ARTHROSCOPICALLY DIAGNOSED WITH
      EROSION OF THE MEDIAL COMPARTMENT: AN ANALYTICAL METHOD COMPARISON STUDY.
AB  - Medial compartment erosion is an advanced stage of medial coronoid disease, an
      important cause of elbow lameness in dogs, with treatment and the expected
      prognosis depending on the extent of the cartilage lesions. The identification of
      specific computed tomographic (CT) findings might facilitate the nonsurgical
      diagnosis and add to treatment decision making. Aims of this retrospective,
      analytical, method comparison study were to describe CT findings in elbows of
      dogs arthroscopically diagnosed with medial compartment erosion and to compare CT
      vs. arthroscopic findings. A total of 56 elbows met inclusion criteria. Elbows
      with focal (n = 13), diffuse (n = 11), and complete (n = 32) erosion were
      compared. Prevalence findings for CT lesions were as follows: periarticular
      osteophytosis (100%), abnormal shape of the medial coronoid process of the ulna
      (96.4%), and subchondral bone defect of the medial part of the humeral condyle
      (MHC; 96.4%). The three groups significantly differed for presence of medial
      coronoid process fragmentation, radial head subchondral bone sclerosis, and
      widening of the humeroulnar joint space. No significant agreement was found
      between CT and arthroscopy for presence of a subchondral bone defect of the MHC.
      A significant agreement was found between CT and arthroscopy for presence of
      fragmentation of the medial coronoid process. However, some of the calcified
      body/fragment(s) visualized on CT in the region of the medial coronoid process
      could not be identified via arthroscopy. Findings indicated that an accurate
      estimation of the extent of the elbow cartilage lesions still requires
      arthroscopic joint inspection.

PMID- 27699922
TI  - Intravenous iron and erythropoiesis-stimulating agents in haemodialysis: A
      systematic review and meta-analysis.
AB  - AIM: Higher dosages of erythropoiesis-stimulating agents (ESAs) have been
      associated with adverse effects. Intravenous iron is used to optimize ESA
      response and reduces ESA doses in haemodialysis patients; this meta-analysis
      evaluates the magnitude of this effect. METHODS: A literature search was
      performed using MEDLINE, Embase and the Cochrane Collaboration Central Register
      of Clinical Trials from inception until December 2014, to identify randomized
      controlled trials of intravenous iron and ESA, in patients undergoing
      haemodialysis for end-stage kidney disease. Dosing of IV iron in concordance with
      the Kidney Disease Improving Global Outcomes guidelines was considered optimal
      iron therapy. RESULTS: Of the 28 randomized controlled trials identified, seven
      met the criteria for inclusion in the meta-analysis. Results of random-effects
      meta-analysis show a statistically significant weighted mean (95% CI) difference
      of -1733 [-3073, -392] units/week in ESA dose for optimal iron versus suboptimal
      iron. The weighted average change in ESA dose was a reduction of 23% (range -7%
      to -55%) attributable to appropriate dosing of intravenous iron. A comparison of
      intravenous iron versus oral iron/no iron (five trials) showed a greater
      reduction in ESA dose, although this did not reach statistical significance
      (weighted mean difference, 95% CI: -2,433 [-5183, 318] units/week). The weighted
      average change in ESA dose across the five trials was a reduction of 31% (range 
      8% to -55%). CONCLUSION: Significant reductions in ESA dosing may be achieved
      with optimal intravenous iron usage in the haemodialysis population, and
      suboptimal iron use may require higher ESA dosing to manage anaemia.

PMID- 27699923
TI  - Age-related cognitive decline coincides with accelerated volume loss of the
      dorsal but not ventral hippocampus in mice.
AB  - Even in the absence of neurodegenerative diseases, progressing age often
      coincides with cognitive decline and morphological changes. However, longitudinal
      studies that directly link these two processes are missing. In this proof-of
      concept study we therefore performed repeated within-subject testing of healthy
      male R26R mice in a spatial learning task in combination with manganese-enhanced
      volumetric MRI analyses at the ages of 8, 16, and 24 months. We grouped the mice
      into good and poor performers (n = 6, each), based on their spatial learning
      abilities at the age of 24 months. Using this stratification, we failed to detect
      a priori volume differences, but observed a significant decrease in total
      hippocampal volume over time for both groups. Interestingly, this volume decrease
      was specific for the dorsal hippocampus and significantly accelerated in poor
      performers between 16 and 24 months of age. This is the first time that
      individual changes in hippocampal volume were traced alongside cognitive
      performance within the same subjects over 11/2 years. Our study points to a
      causal link between volume loss of the dorsal hippocampus and cognitive
      impairments. In addition, it suggests accelerated degenerative processes rather
      than a priori volume differences as determining trajectories of age-related
      cognitive decline. Despite the relatively small sample sizes, the strong
      behavioral and moderate morphological alterations demonstrate the general
      feasibility of longitudinal studies of age-related decline in cognition and
      hippocampus integrity. (c) 2016 Wiley Periodicals, Inc.

PMID- 27699924
TI  - ICD-11 Beta Draft Survey in Japan.

PMID- 27699926
TI  - Retraction.

PMID- 27699925
TI  - Gastric heterotopic pancreas with low grade dysplasia of the ducts.

PMID- 27699927
TI  - Relevance of biomarkers in disease progression in multiple sclerosis.

PMID- 27699928
TI  - Adaptive Chemical Networks under Non-Equilibrium Conditions: The Evaporating
      Droplet.
AB  - Non-volatile solutes in an evaporating drop experience an out-of-equilibrium
      state due to non-linear concentration effects and complex flow patterns. Here, we
      demonstrate a small molecule chemical reaction network that undergoes a rapid
      adaptation response to the out-of-equilibrium conditions inside the droplet
      leading to control over the molecular constitution and spatial arrangement of the
      deposition pattern. Adaptation results in a pronounced coffee stain effect and
      coupling to chemical concentration gradients within the drop is demonstrated.
      Amplification and suppression of network species are readily identifiable with
      confocal fluorescence microscopy. We anticipate that these observations will
      contribute to the design and exploration of out-of-equilibrium chemical systems,
      as well as be useful towards the development of point-of-care medical diagnostics
      and controlled deposition of small molecules through inkjet printing.

PMID- 27699929
TI  - Bovine endometrial cells: a source of mesenchymal stem/progenitor cells.
AB  - Endometrial mesenchymal stem/progenitor cells (eMSCs) are multipotent cells known
      to modulate the immune system and have clinical application for human and animal
      health. This makes these bovines cells attractive for dual use as cellular
      therapy and experimental model. The aim of this study was to isolate, evaluate
      the differentiation potential, immunophenotypic and immunocytochemistry
      characteristics, chromosomal stability, cloning efficiency, and cryopreservation
      response of bovine eMSCs collected in two phases of the estrous cycle. For this,
      cells were isolated and submitted to differentiation for adipogenic and
      osteogenic lineage. The cells were then characterized by flow cytometer (FC)
      (vimentin, CD29, CD44, MHC-II, CD34) and immunocytochemistry (vimentin, pan
      cytokeratin, CD44) and submitted to cytogenetic and cloning efficiency assay. The
      cells were also cryopreserved using two different medium of cryopreservation and
      analyzed by FC for viability, necrosis, late-apoptosis + necrosis, and initial
      apoptosis rates before and after cryopreservation. We obtained homogeneous cell
      populations which have fibroblastic morphology and adherence to plastic. These
      cells expressed high levels of markers CD29, CD44, and vimentin, low expression
      levels for CD34 and no MHC-II. The cells were chromosomally stable (2n = 60) with
      high cloning efficiency and no difference (P > 0.05) between medium of
      cryopreservation or phase was observed after thawing. We showed the presence and
      differentiation potential of bovine eMSCs, with chromosomal stability and great
      response to cryopreservation with both medium, which has implications for build
      biobanks or development of new therapeutic approaches to combat uterine diseases
      or to study.

PMID- 27699931
TI  - Estimating cancer survival - improving accuracy and relevance.

PMID- 27699930
TI  - Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy
      in natalizumab-treated multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Brain atrophy is related to clinical deterioration in
      multiple sclerosis (MS) but its association with intrathecal markers of
      inflammation or neurodegeneration is unclear. Our aim was to investigate whether
      cerebrospinal fluid (CSF) markers of inflammation or neurodegeneration are
      associated with brain volume change in natalizumab-treated MS and whether this
      change is reflected in non-lesional white matter metabolites. METHODS: About 25
      patients with natalizumab-treated MS were followed for 3 years with assessment of
      percentage brain volume change (PBVC) and absolute quantification of metabolites
      with proton magnetic resonance spectroscopy (1 H MRS). Analyses of inflammatory
      [interleukin 1beta (IL-1beta), IL-6, C-X-C motif chemokine 8 (CXCL8), CXCL10,
      CXCL11, C-C motif chemokine 22] and neurodegenerative [neurofilament light
      protein (NFL), glial fibrillary acidic protein, myelin basic protein, tau
      proteins] markers were done at baseline and 1-year follow-up. RESULTS: The mean
      decline in PBVC was 3% at the 3-year follow-up, although mean 1 H MRS metabolite
      levels in non-lesional white matter were unchanged. CSF levels of NFL and tau at
      baseline correlated negatively with PBVC over 3 years (r = -0.564, P = 0.012, and
      r = -0.592, P = 0.010, respectively). CONCLUSIONS: A significant 3-year whole
      brain atrophy was not reflected in mean metabolite change of non-lesional white
      matter. In addition, our results suggest that CSF levels of NFL and tau correlate
      with brain atrophy development and may be used for evaluating treatment response
      in inflammatory active MS.

PMID- 27699932
TI  - Community exposure to hazardous site remediation in rural New Zealand: an exposed
      referent study of serum dioxins and health effects.
AB  - OBJECTIVE: The New Zealand Ministry of Health responded to community concern
      about dioxin exposure during on-site remediation of a pesticide-contaminated
      rural area by commissioning this exposed-referent study of serum dioxins and
      health in local residents. METHODS: All 200 residents were eligible, with age and
      sex matching to demographically comparable referents. Face-to-face interviews
      included questions on health status, health-related quality of life (HRQOL) and
      perceptions about community consultation. Thirty serum samples were obtained,
      eligibility being based on likelihood of exposure and age. Both HRQOL and serum
      outcomes were analysed by the appropriate regression methods. RESULTS: Of 200
      eligible residents, 139 (69.5%) participated, with 139 matched referents. Mapua
      residents had lower physical and psychological HRQOL scores, but no difference in
      health status. 2,3,7,8 TCDD was below the limit of detection in the majority of
      all serum samples, with some congeners being higher in referents. Perceptions of
      the communication process were equivocal. CONCLUSIONS: Both dioxin levels and
      measures of health did not differ significantly between the exposed community and
      controls. Implications for public health: The results suggest neither significant
      dioxin exposure nor community health effects. Oversight by expert panel with
      health expertise, allied to sound communication, may have helped the community
      understand the risks.

PMID- 27699934
TI  - Lymphocyte-depleting induction therapy lowers the risk of acute rejection in
      African American pediatric kidney transplant recipients.
AB  - The use of lymphocyte-depleting induction immunosuppression has been associated
      with a reduction in risk of AR after KT among adult recipients, particularly
      among high-risk subgroups such as AAs. However, data on induction regimen and AR
      risk are lacking among pediatric KT recipients. We examined outcomes among 7884
      first-time pediatric KT recipients using SRTR data (2000-2014). Characteristics
      were compared across race using Wilcoxon rank-sum tests for continuous and chi
      square tests for categorical variables. Risk of AR was estimated using modified
      Poisson regression, stratified by recipient race, adjusting for recipient age,
      gender, BMI, primary diagnosis, number of HLA mismatches, maintenance
      immunosuppression, and donor type. Risk of AR within 1 year was lower in AA
      recipients receiving lymphocyte-depleting induction (ATG or alemtuzumab; RR,
      0.66; 95% CI, 0.52-0.83 P < .001) compared to AA recipients receiving anti-IL-2
      receptor antibody induction. This difference was not seen in non-AA recipients
      receiving lymphocyte-depleting induction (RR, 0.93; 95% CI, 0.81-1.06, P = .26)
      compared to IL-2 induction. These findings support a role for lymphocyte
      depleting induction agents in AA pediatric patients undergoing KT and continued
      use of IL-2 inhibitor induction in non-AA pediatric KT recipients.

PMID- 27699935
TI  - Transplantation of organs from deceased donors with meningitis and encephalitis:
      a UK registry analysis.
AB  - BACKGROUND: Deceased organ donors, where the cause of death is meningitis or
      encephalitis, are a potential concern because of the risks of transmission of a
      potentially fatal infection to recipients. METHODS: Using the UK Transplant
      Registry, a retrospective cohort analysis of deceased organ donors in the UK was
      undertaken to better understand the extent to which organs from deceased donors
      with meningitis and/or encephalitis (M/E) (of both known and unknown cause) have
      been used for transplantation, and to determine the associated recipient
      outcomes. RESULTS: Between 2003 and 2015, 258 deceased donors with M/E were
      identified and the causative agent was known in 188 (72.9%). These donors
      provided 899 solid organs for transplantation (455 kidneys and 444 other organs).
      The only recorded case of disease transmission was from a donor with encephalitis
      of unknown cause at time of transplantation who transmitted a fatal nematode
      infection to 2 kidney transplant recipients. A further 3 patients (2 liver and 1
      heart recipient) died within 30 days of transplantation from a neurological cause
      (cerebrovascular accident) with no suggestion of disease transmission. Overall,
      patient and graft survival in recipients of organs from donors with M/E were
      similar to those for all other types of deceased organ donor. CONCLUSION: Donors
      dying with M/E represent a valuable source of organs for transplantation. The
      risk of disease transmission is low but, where the causative agent is unknown,
      caution is required.

PMID- 27699933
TI  - Effect of AKT3 expression on MYC- and caspase-8-dependent apoptosis caused by
      polo-like kinase inhibitors in HCT 116 cells.
AB  - Polo-like kinase (PLK) is a cell-cycle regulator that is overexpressed in several
      cancer cell types. Polo-like kinase is considered a novel target for cancer
      therapies, and several PLK inhibitors (PLKis), including BI 2536, BI 6727, and
      GSK461364, have been developed. In this study, we established five BI 2536
      resistant cell lines from human colorectal cancer HCT 116 cells, to explore the
      resistance mechanism and identify predictable biomarkers of PLKis. We showed that
      PLKi-induced caspase-8 activation was attenuated in the BI 2536-resistant cell
      lines. We also showed that the expression of P-glycoprotein (P-GP) and AKT3 was
      upregulated, whereas that of MYC was downregulated in some BI 2536-resistant cell
      lines. Expression of P-GP conferred resistance to PLKis, and PLKi-induced
      apoptosis was dependent on MYC and caspase-8 in HCT 116 cells. We also showed for
      the first time that AKT3 suppressed BI 6727-induced caspase-8 activation and
      conferred resistance to PLKis. Collectively, these results indicate that MYC,
      caspase-8, P-GP, and AKT3 play critical roles in PLKi-induced apoptosis.
      Therefore, they are candidate biomarkers of the pharmacological efficacy of
      PLKis.

PMID- 27699936
TI  - Diagnostic accuracy of des-gamma-carboxy prothrombin for hepatocellular carcinoma
      in a French cohort using the Lumipulse(r) G600 analyzer.
AB  - The increasing incidence of hepatocellular carcinoma (HCC) in Western countries
      requests reliable tumour markers for preclinical diagnosis. We evaluated the
      diagnostic accuracy of des-gamma-carboxy prothrombin (DCP), in comparison with
      alpha-fetoprotein (AFP) in a French cohort using a new analyser. One hundred and
      sixty-two patients with virus-related cirrhosis (46 HCC patients and 116
      controls) were recruited in this retrospective proof-of-concept study. DCP was
      measured on new Lumipulse(r) G600 analyzer and AFP on usual Cobas e602 analyzer
      in serum samples that were collected at the time of HCC diagnosis for HCC
      patients or during follow-up for controls. DCP and AFP levels were higher in HCC
      patients. The area under receiver operating characteristic curve was larger for
      DCP than for AFP (0.89 vs 0.77, P=.03). At the cut-off value of 128 mAU/mL,
      sensitivity and specificity for DCP were 74% and 92%. At the cut-off value of 20
      MUg/L, sensitivity and specificity for AFP were 63% and 82%. NRI>0 for the
      association of "AFP+DCP" were 101%, P<.0001, and 23%, P=.03, compared to "AFP" or
      "DCP" alone, respectively. We conclude that DCP outperformed AFP for the
      detection of HCC.

PMID- 27699939
TI  - From the ADAA President.

PMID- 27699937
TI  - The Role of BDNF in the Development of Fear Learning.
AB  - Brain-derived neurotrophic factor (BDNF) is a growth factor that is dynamically
      expressed in the brain across postnatal development, regulating neuronal
      differentiation and synaptic plasticity. The neurotrophic hypothesis of
      psychiatric mood disorders postulates that in the adult brain, decreased BDNF
      levels leads to altered neural plasticity, contributing to disease. Although BDNF
      has been established as a key factor regulating the critical period plasticity in
      the developing visual system, it has recently been shown to also play a role in
      fear circuitry maturation, which has implications for the emergence of fear
      related mood disorders. This review provides a detailed overview of developmental
      changes in expression of BDNF isoforms, as well as their receptors across
      postnatal life. In addition, recent developmental studies utilizing a genetic
      BDNF single nucleotide polymorphism (Val66Met) knock-in mouse highlight the
      impact of BDNF on fear learning during a sensitive period spanning the transition
      into adolescent time frame. We hypothesize that BDNF in the developing brain
      regulates fear circuit plasticity during a sensitive period in early adolescence,
      and alterations in BDNF expression (genetic or environmental) have a persistent
      impact on fear behavior and fear-related disorders.

PMID- 27699938
TI  - Kappa-Opioid Antagonists for Psychiatric Disorders: From Bench to Clinical
      Trials.
AB  - Kappa-opioid receptor (KOR) antagonists are currently being considered for the
      treatment of a variety of neuropsychiatric conditions, including depressive,
      anxiety, and substance abuse disorders. A general ability to mitigate the effects
      of stress, which can trigger or exacerbate these conditions, may explain their
      putative efficacy across such a broad array of conditions. The discovery of their
      potentially therapeutic effects evolved from preclinical research designed to
      characterize the molecular mechanisms by which experience causes neuroadaptations
      in the nucleus accumbens (NAc), a key element of brain reward circuitry. This
      research established that exposure to drugs of abuse or stress increases the
      activity of the transcription factor CREB (cAMP response element binding protein)
      in the NAc, which leads to elevated expression of the opioid peptide dynorphin
      that in turn causes core signs of depressive- and anxiety-related disorders.
      Disruption of KORs-the endogenous receptors for dynorphin-produces antidepressant
      and anxiolytic-like actions in screening procedures that identify standard drugs
      of these classes, and reduces stress effects in tests used to study addiction and
      stress-related disorders. Although interest in this target is high, prototypical
      KOR antagonists have extraordinarily persistent pharmacodynamic effects that
      complicate clinical trials. The development of shorter acting KOR antagonists
      together with more rapid designs for clinical trials may soon provide insight on
      whether these drugs are efficacious as would be predicted by preclinical work. If
      successful, KOR antagonists would represent a unique example in psychiatry where
      the therapeutic mechanism of a drug class is understood before it is shown to be
      efficacious in humans.

PMID- 27699942
TI  - Psychobiology of the intersection and divergence of depression and anxiety.

PMID- 27699940
TI  - Amygdala-Cortical Connectivity: Associations with Anxiety, Development, and
      Threat.
AB  - BACKGROUND: Amygdala-prefrontal cortex (PFC) functional connectivity may be
      influenced by anxiety and development. A prior study on anxiety found age
      specific dysfunction in the ventromedial PFC (vmPFC), but not amygdala,
      associated with threat-safety discrimination during extinction recall (Britton et
      al.). However, translational research suggests that amygdala-PFC circuitry
      mediates responses following learned extinction. Anxiety-related perturbations
      may emerge in functional connectivity within this circuit during extinction
      recall tasks. The current report uses data from the prior study to examine how
      anxiety and development relate to task-dependent amygdala-PFC connectivity.
      METHODS: Eighty-two subjects (14 anxious youths, 15 anxious adults, 25 healthy
      youths, 28 healthy adults) completed an extinction recall task, which directed
      attention to different aspects of stimuli. Generalized psychophysiological
      interaction analysis tested whether task-dependent functional connectivity with
      anatomically defined amygdala seed regions differed across anxiety and age
      groups. RESULTS: Whole-brain analyses showed significant interactions of anxiety,
      age, and attention task (i.e., threat appraisal, explicit threat memory, physical
      discrimination) on left amygdala functional connectivity with the vmPFC and
      ventral anterior cingulate cortex (Talairach XYZ coordinates: -16, 31, -6 and 1,
      36, -4). During threat appraisal and explicit threat memory (vs. physical
      discrimination), anxious youth showed more negative amygdala-PFC coupling,
      whereas anxious adults showed more positive coupling. CONCLUSIONS: In the context
      of extinction recall, anxious youths and adults manifested opposite directions of
      amygdala-vmPFC coupling, specifically when appraising and explicitly remembering
      previously learned threat. Future research on anxiety should consider
      associations of both development and attention to threat with functional
      connectivity perturbations.

PMID- 27699943
TI  - Treatment for Anhedonia: A Neuroscience Driven Approach.
AB  - Anhedonia, or loss of interest or pleasure in usual activities, is characteristic
      of depression, some types of anxiety, as well as substance abuse and
      schizophrenia. Anhedonia is a predictor of poor long-term outcomes, including
      suicide, and poor treatment response. Because extant psychological and
      pharmacological treatments are relatively ineffective for anhedonia, there is an
      unmet therapeutic need for this high-risk symptom. Current psychological and drug
      treatments for anxiety and depression focus largely on reducing excesses in
      negative affect rather than improving deficits in positive affect. Recent
      advances in affective neuroscience posit that anhedonia is associated with
      deficits in the appetitive reward system, specifically the anticipation,
      consumption, and learning of reward. In this paper, we review the evidence for
      positive affect as a symptom cluster, and its neural underpinnings, and introduce
      a novel psychological treatment for anxiety and depression that targets
      appetitive responding. First, we review anhedonia in relation to positive and
      negative valence systems and current treatment approaches. Second, we discuss the
      evidence linking anhedonia to biological, experiential, and behavioral deficits
      in the reward subsystems. Third, we describe the therapeutic approach for
      Positive Affect Treatment (PAT), an intervention designed to specifically target
      deficits in reward sensitivity.

PMID- 27699941
TI  - Treatment and Prevention of Depression and Anxiety in Youth: Test of Cross-Over
      Effects.
AB  - Anxiety and depression are highly comorbid and share several common etiological
      processes. Therefore, it may be more efficient to develop interventions that
      treat or prevent these problems together rather than as separate entities. The
      present meta-analytic review examined whether interventions for children and
      adolescents that explicitly targeted either anxiety or depression showed
      treatment specificity or also impacted the other outcome (i.e. cross-over
      effects). We addressed this question both within the same type of study (i.e.
      treatment, prevention) and across study types. Only randomized controlled trials
      (RCTs) that assessed both constructs with dimensional measures were included in
      this review. For treatment studies, RCTs targeting anxiety (n = 18) showed
      significant effects on both anxious and depressive symptoms, although more
      strongly on anxiety than depression; similarly, RCTs treating depression (n = 9)
      yielded significant effects on both depressive and anxious symptoms, but stronger
      effects on depression than anxiety. Thus, there were cross-over effects in
      treatments purportedly targeting either anxiety or depression, and also treatment
      specificity, such that larger effects were seen for the target problem at which
      the treatment was aimed. Anxiety prevention studies (n = 14) significantly
      affected anxious, but not depressive symptoms, indicating no cross-over effect of
      anxiety prevention trials on depression. For depression prevention studies (n =
      15), the effects were not significant for either depressive or anxiety symptoms,
      although the effect was significantly larger for depressive than for anxious
      symptoms. Post-hoc analyses revealed that the effect on depressive symptoms was
      significant in depression preventions trials of targeted but not universal
      samples. Implications for transdiagnostic interventions are discussed.

PMID- 27699944
TI  - Bacteria induce pigment formation in the basidiomycete Serpula lacrymans.
AB  - Basidiomycete fungi are characterized ecologically for their vital functional
      role in ecosystem carbon recycling and chemically for their capacity to produce a
      diverse array of small molecules. Chromophoric natural products derived from the
      quinone precursor atromentin, such as variegatic acid and involutin, have been
      shown to function in redox cycling. Yet, in the context of an inter-kingdom
      natural system these pigments are still elusive. Here, we co-cultured the model
      saprotrophic basidiomycete Serpula lacrymans with an ubiquitous terrestrial
      bacterium, either Bacillus subtilis, Pseudomonas putida, or Streptomyces
      iranensis. For each, there was induction of the gene cluster encoding a non
      ribosomal peptide synthetase-like enzyme (atromentin synthetase) and an
      aminotransferase which together produce atromentin. Correspondingly, during co
      culturing there was an increase in secreted atromentin-derived pigments, i.e.,
      variegatic, xerocomic, isoxerocomic, and atromentic acid. Bioinformatic analyses
      from 14 quinone synthetase genes, twelve of which are encoded in a cluster,
      identified a common promoter motif indicating a general regulatory mechanism for
      numerous basidiomycetes.

PMID- 27699945
TI  - Cooperation in lovers: An fNIRS-based hyperscanning study.
AB  - This study investigated interactive exchange in lovers and the associated
      interpersonal brain synchronization (IBS) using functional near-infrared
      spectroscopy (fNIRS)-based hyperscanning. Three types of female-male dyads,
      lovers, friends, and strangers, performed a cooperation task during which brain
      activity was recorded in right frontoparietal regions. We measured better
      cooperative behavior in lover dyads compared with friend and stranger dyads.
      Lover dyads demonstrated increased IBS in right superior frontal cortex, which
      also covaried with their task performance. Granger causality analyses in lover
      dyads revealed stronger directional synchronization from females to males than
      from males to females, suggesting different roles for females and males during
      cooperation. Our study refines the theoretical explanation of romantic
      interaction between lovers. Hum Brain Mapp 38:831-841, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27699946
TI  - Time course of hepatitis E-specific antibodies in adults.
AB  - Hepatitis E virus (HEV) is highly endemic in industrialized countries, but there
      is a lack of knowledge on individual and overall antibody concentration dynamics.
      The aim of this study was to characterize longitudinal concentration changes of
      anti-HEV immunoglobulin G (anti-HEV IgG) by enzyme immunoassay (EIA). In total,
      199 serum samples collected from 45 subjects over 18 years were analysed. A wide
      range of anti-HEV IgG levels was found. Overall, anti-HEV IgG significantly
      decreased after an observation period of at least 5 years. One negative
      seroconversion was observed. Four individual profiles suggested single and even
      multiple HEV reinfections despite pre-existing HEV antibodies.

PMID- 27699947
TI  - Carbon-Nitrogen Bond Cleavage by a Thorium-NHC-bpy Complex.
AB  - Actinide complexes demonstrate unparalleled reactivity towards small molecules.
      However, utilizing these powerful transformations in a predictable and deliberate
      manner remains challenging. Therefore, developing actinide systems that not only
      perform noteworthy chemistry but also demonstrate controllable reactivity is a
      key goal. We describe a bis(NHC)borate thorium-bpy complex (1) that is capable of
      reductively cleaving the R-NC bond in a series of organic isocyanides. In
      contrast to most actinide-mediated bond activations, the dealkylation event
      mediated by 1 is remarkably general and yields very well-defined products that
      assist in mechanistic elucidation. Synthesis of the rearranged but-3-enyl product
      from the reaction of 1 and cyclopropylmethyl isocyanide supports the notion of a
      radical-based mechanism.

PMID- 27699949
TI  - Thoughts on fatigue in Parkinson's disease (and other disorders).

PMID- 27699948
TI  - Reduced phosphorylation of ribosomal protein S6 is associated with sensitivity to
      MEK inhibition in gastric cancer cells.
AB  - Gastric cancer (GC) is characterized by amplifications of receptor tyrosine
      kinases (RTK) and KRAS, therefore, targeting of the RTK/KRAS downstream pathways
      could help to broaden the applicability of molecular targeted therapy for GC. We
      assembled a panel of 48 GC cell lines and screened predictors of responsiveness
      to inhibition of the RAF/MEK/ERK pathway, one of the RTK/KRAS downstream
      pathways. We found that GC cells with MET amplification or KRAS mutation, but not
      amplification, tended to be sensitive to MEK inhibition. However, several cell
      lines without RTK/KRAS alterations also showed high sensitivity to MEK
      inhibition. We then focused on the phosphorylation of RTK/KRAS downstream
      molecules to screen for predictors' sensitivity to MEK inhibition. We found that
      the phosphorylation level of mammalian target of rapamycin complex 1 (mTORC1)
      downstream molecules, including p70S6K, 4EBP1, and S6, was significantly
      associated with sensitivity to MEK inhibition in GC cells (P < 0.05), suggesting
      that mTORC1 activity is related to the sensitivity to MEK inhibition.
      Furthermore, the change in mTORC1 activity after MEK inhibition was also
      significantly associated with this sensitivity (P < 0.001). Among the mTORC1
      downstream molecules, the change in S6 phosphorylation (pS6) showed the most
      significant correlation with sensitivity. Using xenograft models derived from
      highly sensitive and resistant cell lines, we found specific reduction of pS6 in
      xenografts from highly sensitive cell lines after 6 h of treatment with an MEK
      inhibitor. Thus, our data suggest the potential clinical applicability of an MEK
      inhibitor for a proportion of GC patients who could be selected on the basis of
      pS6 change after MEK inhibition.

PMID- 27699951
TI  - Muscle layer histopathology and manometry pattern of primary esophageal motility
      disorders including achalasia.
AB  - BACKGROUND: Histopathology of muscularis externa in primary esophageal motility
      disorders has been characterized previously. We aimed to correlate the results of
      high-resolution manometry with those of histopathology. METHODS: During peroral
      endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients
      with primary esophageal motility disorders. Immunohistochemical staining for c
      kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin
      Eosin and Azan-Mallory staining were used to detect muscle atrophy, inflammation,
      and fibrosis, respectively. KEY RESULTS: Slides from 30 patients with the
      following motility disorders were analyzed: achalasia (type I: 14, type II: 5,
      type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO),
      four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were
      preserved in high numbers in type III achalasia (n=9.4+/-1.2 cells/high power
      field [HPF]), compared to types I (n=3.7+/-0.3 cells/HPF) and II (n=3.5+/-1.0
      cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and
      not in other types of achalasia, OO, or DES. Four of five patients with JE and NE
      had severe inflammation with eosinophilic infiltration of the esophageal muscle
      layer (73.8+/-50.3 eosinophils/HPF) with no epithelial eosinophils. One patient
      with JE showed a visceral myopathy pattern. CONCLUSIONS & INFERENCES: Compared to
      types I and II, type III achalasia showed preserved ICCs, with variable data
      regarding DES and OO. In disorders considered as primary esophageal motility
      disorders, a disease category exists, which shows eosinophilic infiltration in
      the esophageal muscle layer with no eosinophils in the epithelium.

PMID- 27699950
TI  - Improving qPCR methodology for detection of foaming bacteria by analysis of broad
      spectrum primers and a highly specific probe for quantification of Nocardia spp.
      in activated sludge.
AB  - AIMS: To develop qPCR broad-spectrum primers combined with a Nocardia genus
      specific probe for the identification of a broad spectrum of Nocardia spp. and to
      analyse the effects of using this developed primer and probe set on the ability
      to quantify Nocardia spp. in mixed DNA. METHODS AND RESULTS: The consequences of
      using a degenerative primer set and species-specific probe for the genus Nocardia
      on qPCR assays were examined using DNA extracts of pure cultures and activated
      sludge. The mixed DNA extracts where the target organism Nocardia flavorosea
      concentration ranged from 5 * 102 to 5 * 106 copies per reaction, while the
      background organism's DNA (Mycobacterium bovis) concentration was held at 5 * 106
      copies per reaction, only produced comparable cycle threshold florescence levels
      when N. flavorosea concentration was greater than or equal to the background
      organism concentration. When concentrations of N. flavorosea were lowered in
      increments of 1 log, while holding M. bovis concentrations constant at 5 * 106
      copies per reaction, all assays demonstrated delayed cycle threshold values with
      a maximum 34.6-fold decrease in cycle threshold at a ratio of 106 M. bovis: 102
      N. flavorosea copies per reaction. CONCLUSIONS: The data presented in this study
      indicated that increasing the ability of a primer set to capture a broad group of
      organisms can affect the accuracy of quantification even when a highly specific
      probe is used. This study examined several applications of molecular tools in
      complex communities such as evaluating the effect of mispriming vs interference.
      It also elucidates the importance of understanding the community genetic make-up
      on primer design. SIGNIFICANCE AND IMPACT OF THE STUDY: Degenerative primers are
      very useful in amplifying bacterial DNA across genera, but reduce the efficiency
      of qPCR reactions. Therefore, standards that address closely related background
      species must be used to obtain accurate qPCR results.

PMID- 27699952
TI  - Recognition of 1,3-Butadiene by a Porous Coordination Polymer.
AB  - The separation of 1,3-butadiene from C4 hydrocarbon mixtures is imperative for
      the production of synthetic rubbers, and there is a need for a more economical
      separation method, such as a pressure swing adsorption process. With regard to
      adsorbents that enable C4 gas separation, [Zn(NO2 ip)(dpe)]n (SD-65; NO2 ip=5
      nitroisophthalate, dpe=1,2-di(4-pyridyl)ethylene) is a promising porous material
      because of its structural flexibility and restricted voids, which provide unique
      guest-responsive accommodation. The 1,3-butadiene-selective sorption profile of
      SD-65 was elucidated by adsorption isotherms, in situ PXRD, and SSNMR studies and
      was further investigated by multigas separation and adsorption-desorption-cycle
      experiments for its application to separation technology.

PMID- 27699953
TI  - Ligand and Metal Effects on the Stability and Adsorption Properties of an
      Isoreticular Series of MOFs Based on T-Shaped Ligands and Paddle-Wheel Secondary
      Building Units.
AB  - The synthesis of stable porous materials with appropriate pore size and shape for
      desired applications remains challenging. In this work a combined
      experimental/computational approach has been undertaken to tune the stability
      under various conditions and the adsorption behavior of a series of MOFs by
      subtle control of both the nature of the metal center (Co2+ , Cu2+ , and Zn2+ )
      and the pore surface by the functionalization of the organic linkers with amido
      and N-oxide groups. In this context, six isoreticular MOFs based on T-shaped
      ligands and paddle-wheel units with ScD0.33 topology have been synthesized. Their
      stabilities have been systematically investigated along with their ability to
      adsorb a wide range of gases (N2 , CO2 , CH4 , CO, H2, light hydrocarbons (C1 -C4
      )) and vapors (alcohols and water). This study has revealed that the MOF
      frameworks based on Cu2+ are more stable than their Co2+ and Zn2+ analogues, and
      that the N-oxide ligand endows the MOFs with a higher affinity for CO2 leading to
      excellent selectivity for this gas over other species.

PMID- 27699954
TI  - Research Involving Health Providers and Managers: Ethical Issues Faced by
      Researchers Conducting Diverse Health Policy and Systems Research in Kenya.
AB  - There is a growing interest in the ethics of Health Policy and Systems Research
      (HPSR), and especially in areas that have particular ethical salience across
      HPSR. Hyder et al (2014) provide an initial framework to consider this, and call
      for more conceptual and empirical work. In this paper, we respond by examining
      the ethical issues that arose for researchers over the course of conducting three
      HPSR studies in Kenya in which health managers and providers were key
      participants. All three studies involved qualitative work including observations
      and individual and group interviews. Many of the ethical dilemmas researchers
      faced only emerged over the course of the fieldwork, or on completion, and were
      related to interactions and relationships between individuals operating at
      different levels or positions in health/research systems. The dilemmas reveal
      significant ethical challenges for these forms of HPSR, and show that potential
      'solutions' to dilemmas often lead to new issues and complications. Our
      experiences support the value of research ethics frameworks, and suggest that
      these can be enriched by incorporating careful consideration of context embedded
      social relations into research planning and conduct. Many of these essential
      relational elements of ethical practice, and of producing quality data, are given
      stronger emphasis in social science research ethics than in epidemiological,
      clinical or biomedical research ethics, and are particularly relevant where
      health systems are understood as social and political constructs. We conclude
      with practical and research implications.

PMID- 27699955
TI  - UV-Induced Disulfide Formation and Reduction for Dynamic Photopatterning.
AB  - UV-induced disulfide formation (UV-DF) and disulfide reduction (UV-DR) reactions
      for surface functionalization and dynamic photopatterning are presented. Both
      photochemical reactions allow for the spatially and temporally controlled,
      reversible transition between thiol- and disulfide-functionalized surfaces. The
      dynamic photopatterning strategy was demonstrated by the UV-induced attachment,
      exchange, and detachment on thiol-modified substrates.

PMID- 27699956
TI  - Mimicking the Aromatic-Ring-Cleavage Activity of Gentisate-1,2-Dioxygenase by a
      Nonheme Iron Complex.
AB  - Gentisate-1,2-dioxygenase (GDO), a nonheme iron enzyme in the cupin superfamily,
      catalyzes the cleavage of the aromatic-ring of 2,5-dihydroxybenzoic acid
      (gentisic acid) to form maleylpyruvic acid in the microbial aerobic degradation
      of aromatic compounds. To develop a functional model of GDO, we have isolated a
      nonheme iron(II) complex, [(TpPh2 )FeII (DHN-H)] (TpPh2 =hydrotris(3,5
      diphenylpyrazole-1-yl)borate, DHN-H=1,4-dihydroxy-2-naphthoate). In the reaction
      with O2 , the biomimetic complex oxidatively cleaves the aromatic ring of the
      coordinated substrate with the incorporation of both the oxygen atoms from
      molecular oxygen into the cleavage product. The presence of para-hydroxy group on
      the substrate plays a crucial role in directing the aromatic-ring cleaving
      reaction.

PMID- 27699957
TI  - The Vulnerability of Study Participants in the Context of Transnational
      Biomedical Research: From Conceptual Considerations to Practical Implications.
AB  - Outsourcing clinical trials sponsored by pharmaceutical companies from
      industrialized countries to low- (middle)-income countries - summarized as
      transnational biomedical research (TBR) - has lead to many concerns about ethical
      standards. Whether study participants are particularly vulnerable is one of those
      concerns. However, the concept of vulnerability is still vague and varies in its
      definition. Despite the fact that important international ethical guidelines such
      as the Declaration of Helsinki by the World Medical Association or the Ethical
      Guidelines for Biomedical Research Involving Human Subjects by the Council of
      International Organizations of Medical Sciences refer to vulnerability as ethical
      principle, each of their approaches are different. To overcome these
      shortcomings, we analyze and unite different approaches of vulnerability and
      develop practical criteria in order to operationalize the concept especially for
      the context of TBR. These criteria refer to the context of a study as well as the
      characteristics and the current living situation of study participants. Based on
      a case study of an HIV-vaccine-trial conducted in India we demonstrate how those
      criteria can be applied in a retrospective way to identify potential ethical
      conflicts. The criteria can also indicate a prospective function for ethical pre
      assessment. For this, we provide an outlook for three major topics: 1.
      Vulnerability as a normative concept: Different ways of protection; 2. The
      relevance of transparency and 3. Vulnerability as an instrument to increase
      decision participation of human subjects.

PMID- 27699958
TI  - Effects of Additional Acid Etching on the Dentin Bond Strengths of One-Step Self
      Etch Adhesives Applied to Primary Teeth.
AB  - OBJECTIVES: The aim of this study was to evaluate the bond strengths of one-step
      self-etch adhesives applied to primary tooth dentin with and without additional
      acid etching. MATERIALS AND METHODS: In total, 154 specimens were prepared using
      50 naturally exfoliated primary molars. Four commercial one-step self-etch
      adhesives were used in this study: ScotchbondTM Universal, All-Bond UniversalTM,
      AdperTM PromptTM L-PopTM, and Clearfil S3 BondTM. Two etch-and-rinse adhesives,
      Prime & Bond(r) NTTM and ScotchbondTM Multi-Purpose, served as controls.
      Microtensile bond strength tests were performed for specimens treated with the
      one-step self-etch adhesives with and without additional acid etching and those
      treated with the two etch-and-rinse adhesives. RESULTS: All one-step self-etch
      adhesives except Adper Prompt L-Pop exhibited increased microtensile bond
      strength values (p < 0.05) with additional acid etching. A nonsignificant
      interaction was observed between the type of self-etch adhesive and additional
      acid etching (p = 0.056). Bond strength comparisons between the self-etch
      adhesives used without additional acid etching and the etch-and-rinse adhesives
      revealed significantly higher values for Prime & Bond NT than for All-Bond
      Universal(r) (p < 0.05). However, there were no significant differences between
      any etch-and-rinse adhesive and self-etch adhesive used with additional acid
      etching, although Clearfil S3 Bond showed greater strength than Adper Prompt L
      Pop. CONCLUSIONS: Our results suggest that additional acid etching increases the
      bond strength of most one-step self-etch adhesives applied to primary tooth
      dentin. CLINICAL SIGNIFICANCE: Additional acid etching of enamel and dentin can
      be recommended to increase the bond strength of one-step self-etch adhesives
      applied to primary teeth. (J Esthet Restor Dent 29:110-117, 2017).

PMID- 27699960
TI  - Advantages of self-administration of injectable contraceptives.

PMID- 27699959
TI  - Gender differences in the inflammatory cytokine and chemokine profiles induced by
      binge ethanol drinking in adolescence.
AB  - Heavy binge drinking in adolescence can cause long-term cognitive and behavioral
      dysfunctions. Recent experimental evidence indicates the participation of immune
      system activation in the effects of ethanol in the adolescent brain and suggests
      gender differences. The present study aims to assess plasma cytokine and
      chemokine levels in male and female adolescents and young adults during acute
      alcohol intoxication and to correlate these results with the toll-like receptor 4
      (TLR4) response. The potential role of the TLR4 signaling response was also
      assessed in plasma and prefrontal cortex (PFC) of adolescent wild-type and TLR4
      knockout male and female mice with binge ethanol treatment. The results showed
      that alcohol intoxication increased the plasma levels of several cytokine and
      chemokine [interferon-gamma, interleukin (IL)-10, IL-17A, IL-1beta, IL-2, IL-4,
      IL-6, IL-8, fractalkine, monocyte chemoattractant protein 1 (MCP-1) and
      macrophage inflammatory protein 1alpha (MIP-1alpha)] and the upregulation of TLR4
      mRNA levels occurred in intoxicated females, while elevation of colony
      stimulating factor was only observed in the plasma of males. In wild-type female
      adolescent mice, intermittent ethanol treatment increased the levels of several
      cytokines (IL-17A and IL-1beta) and chemokines (MCP-1, MIP-1alpha and
      fractalkine) in PFC and in serum (IL-17A, MCP-1 and MIP-1alpha), but significant
      differences in the fractalkine levels in PFC were observed only in male mice. No
      changes in serum or prefrontal cortex cytokine and chemokine levels were noted in
      ethanol-treated male or female TLR4-knockout mice. Our findings revealed that
      females are more vulnerable than males to inflammatory effects of binge ethanol
      drinking and suggested that TLR4 is an important target of ethanol-induced
      inflammation and neuroinflammation in adolescence.

PMID- 27699961
TI  - Pheophytin a isolated from the seagrass Syringodium isoetifolium plausibly blocks
      umuC proteins of select bacterial pathogens, in silico.
AB  - AIMS: This investigation is designed to evaluate the antibacterial efficiency of
      the noodle grass Syringodium isoetifolium, which is commonly found in the Indian
      coastal waters. Also, this study characterizes the active compound and predicts
      the mode of action in silico. METHODS AND RESULTS: Human pathogenic bacteria were
      treated with crude metabolites of S. isoetifolium. The potent fraction b was
      analysed by UV/VIS, Spectroscopy RP-HPLC, FT-IR, ESI-Mass and 1 H and 13 C NMRs
      and determined to be a hydrate of pheophytin a (C55 H74 N4 O6 ). The isolated
      compound Pheo had MIC values of 6.2 +/- 0.7 (Salmonella typhi) and 12.5 +/- 0.8
      (Escherichia coli and Pseudomonas aeruginosa) MUg ml-1 . Molecular docking
      studies of the compound were done to find the binding sites on the pathogens
      using a Molegro Virtual Docker platform. Pheo targets umuC proteins by binding
      compactly to five amino acid residues with interaction energy of -3.66 and a
      Moldock score of -160.175. CONCLUSIONS: Hence, we conclude that pheophytin a,
      besides being an accessory photosynthetic pigment, also has proven to be
      antibacterial against human pathogens. Lesser MIC values with definite binding
      sites predicted in silico are suggestive of a precise of action for this
      compound. SIGNIFICANCE AND IMPACT OF THE STUDY: Easy extraction methods of the
      active compound that has a definite target render this under-explored seagrass a
      good source of antibacterial compound against human pathogenic bacteria. This
      learning may favour more researches in this unexplored area to build up Pheo
      based natural products as antibiotic therapies.

PMID- 27699962
TI  - Palladium-Catalyzed Arylation of Carbasugars Enables the Discovery of Potent and
      Selective SGLT2 Inhibitors.
AB  - Selective inhibition of the transporter protein sodium-glucose cotransporter 2
      (SGLT2) has emerged as a promising way to control blood glucose level in diabetes
      patients. Reported herein is a short and convergent synthetic route towards some
      small-molecule SGLT2 inhibitors by a chemo- and diastereospecific palladium
      catalyzed arylation reaction. This synthetic strategy enabled the discovery of
      two highly selective and potent SGLT2 inhibitors, thereby paving the way towards
      the development of carbasugar SGLT2 inhibitors as potential
      antidiabetic/antitumor agents.

PMID- 27699963
TI  - The (+)-cis- and (+)-trans-Olibanic Acids: Key Odorants of Frankincense.
AB  - Frankincense (olibanum) is one of the oldest aromatic materials used by humans,
      but the key molecular constituents contributing to its characteristic odor
      remained unknown. Reported herein is the discovery that (1S,2S)-(+)-trans- and
      (1S,2R)-(+)-cis-2-octylcyclopropyl-1-carboxylic acids are highly potent and
      substantive odorants occurring in ppm amounts in all of the frankincense samples
      analyzed, even those showing radically different volatile compositions. These
      cyclopropyl-derived acids provide the very characteristic old churchlike endnote
      of the frankincense odor.

PMID- 27699964
TI  - Comparison of different consensuses of BTXA in different countries.
AB  - The most international dosing guidelines on the use of botulinum toxin type A
      (BTXA) drugs support a 1:1 dose relationship between OnaBTXA and IncoBTXA and
      1:2.5 between OnaBTXA and AboBTXA. However, different facial zones demonstrate
      different doses conversion ratios. The comparative analysis of nine consensuses
      on the use of Abo-, Ona-, and IncoBTXA in the United States, Russia, and Europe
      has been performed. We conducted a review of publications adopting the key words
      "botulinum toxin consensus," "botulinum toxin guideline." Information search has
      been carried out primarily in specialized databases (DB). To find the relevant
      RCTs and guidelines/consensuses, the following databases were used: PubMed and
      Medline that were screened up to May 2008. Results regarding dose ratios for
      OnaBTXA:AboBTXA and IncoBTXA:AboBTXA showed that in most cases it is
      characterized both by increase and by decrease compared to the ratio of 1:2.5.
      The mean value of dose ratios OnaBTXA:AboBTXA adopted in the United States is
      1:2.8. The ratio IncoBTXA:AboBTXA according to international and Russian data is
      1:1.9. There are some differences in clinical approach of BTXA use in certain
      countries. In Russia, low doses are recommended for "crow's feet" and forehead.
      The US consensus recommends a higher dosage to correct perioral wrinkles. Despite
      many years of experience in using BTXA, there is no strict international
      uniformity of clinical guidelines. The recommended doses for the individual areas
      of the face may differ in different countries. Therefore, physicians in their
      practice should be guided not by international consensuses, but prefer a national
      guidelines.

PMID- 27699965
TI  - Norovirus infection in solid organ transplant recipients: a single-center
      retrospective study.
AB  - BACKGROUND: Norovirus (NoV) is gaining recognition as an important cause of
      diarrhea among solid organ transplant (SOT) recipients, but existing studies have
      been limited by a small sample size. METHODS: We conducted a retrospective study
      of all adult SOT recipients diagnosed with NoV between 2006 and 2013 and compared
      their data to that of adult SOT recipients with diarrhea who tested negative for
      NoV during that time. RESULTS: A total of 192 patients with diarrhea had stool
      NoV testing as part of their work-up during the study period; of these patients,
      35% (67) tested positive for NoV. Of patients with diarrhea without NoV,
      Clostridium difficile (25%) and cytomegalovirus (12%) were the most commonly
      identified infectious cause of diarrhea. Diarrheal duration was significantly
      protracted in NoV patients, with an average of 241 days vs 75 days in the control
      group (P=.0007). One patient death and 2 graft failures were related to the NoV
      illness within the first month after the onset of diarrhea, and 30% of NoV
      patients had a >=20% increase in creatinine within 1 year of diagnosis. These
      outcomes did not differ significantly from those of SOT patients with diarrhea in
      the non-NoV group. CONCLUSIONS: NoV is a common cause of diarrhea among SOT
      recipients at our institution and is responsible for a very prolonged course of
      chronic diarrhea.

PMID- 27699966
TI  - Does the emphasis on caring within nursing contribute to nurses' silence about
      practice issues?

PMID- 27699968
TI  - Directed Evolution of Iridium-Substituted Myoglobin Affords Versatile Artificial
      Metalloenzymes for Enantioselective C-C Bond-Forming Reactions.
AB  - Upgrading myoglobin with iridium: A metal-substitution strategy has been used to
      afford a repurposed myoglobin for challenging cyclopropanation and intramolecular
      C-H activation reactions. The performance of the iridium-loaded myoglobin (orange
      sphere) was improved through directed evolution of eight active-site residues
      (yellow surface).

PMID- 27699969
TI  - Monitoring Salmonella, Campylobacter, Escherichia coli and Staphylococcus aureus
      in traditional free-range 'Label Rouge' broiler production: a 23-year survey
      programme.
AB  - AIM: 'Label Rouge' broiler free-range carcasses have been monitored since 1991,
      and broiler flocks since 2010, for contamination by the main foodborne zoonotic
      bacteria. METHODS AND RESULTS: Initially, the monitoring plan mainly focused on
      the surveillance of Salmonella, and on indicators of the overall microbiological
      quality of free-range broiler carcasses such as Staphylococcus aureus and
      coliforms, but was extended in 2007 to include Campylobacter enumeration on
      carcasses and in 2010, to Salmonella in the environment of live birds. Salmonella
      contamination of free-range broiler carcasses rose to a peak of 16% in 1994 but
      less than 1% of carcasses are now regularly found to be positive. Indicators of
      the overall microbiological quality of carcasses are also improving. These
      results correlate with the low prevalence of Salmonella in free-range broiler
      breeding and production flocks, and with the continuous improvement of hazard
      analysis and critical control points in slaughterhouses, the implementation of a
      good manufacturing practice guide since 1997 and the application of EU
      regulations on Salmonella since 1998 in France. Regarding Campylobacter counts on
      carcasses, the situation has been improving continuously over the last few years,
      even if 2.5% of the carcasses are still contaminated by more than 1000
      Campylobacter per g of skin. CONCLUSIONS: Although the current control system
      focusing on Salmonella is based on firm epidemiologic data and offers effective
      means of control (e.g. slaughtering of positive breeder flocks), existing
      information on Campylobacter makes it more difficult to formulate an effective
      control plan for free-range broilers, due to their particular exposure to
      environmental contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: This long-term
      surveillance programme provided an extended view of the evolution of the
      contamination of free-range broilers and a direct measurement of the impact of
      mandatory and profession-driven interventions on the microbiological quality of
      carcasses.

PMID- 27699973
TI  - Transition-Metal-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation:
      Sustainable Chemistry to Access Bioactive Molecules.
AB  - Over the last few decades, the development of new and highly efficient synthetic
      methods to obtain chiral compounds has become an increasingly important and
      challenging research area in modern synthetic organic chemistry. In this account,
      we review recent work from our laboratory toward the synthesis of valuable chiral
      building blocks through transition-metal-catalyzed asymmetric hydrogenation and
      transfer hydrogenation of C=O, C=N and C=C bonds. Application to the synthesis of
      biologically relevant products is also described.

PMID- 27699971
TI  - Robot-assisted approach improves surgical outcomes in obese patients undergoing
      partial nephrectomy.
AB  - OBJECTIVES: To assess the impact of approach on surgical outcomes in otherwise
      healthy obese patients undergoing partial nephrectomy for small renal masses.
      PATIENTS AND METHODS: Using our institutional partial nephrectomy database, we
      abstracted data on otherwise healthy (Charlson comorbidity score <=1 and
      bilateral kidneys), obese patients (body mass index >30 kg/m2 ) with small renal
      masses (<4 cm) treated between 2011 and 2015. The primary outcomes were intra
      operative transfusion, operating time, length of hospital stay (LOS), and
      postoperative complications. The association between approach, open (OPN) vs
      robot-assisted partial nephrectomy (RAPN), and outcomes was assessed by
      univariable and multivariable logistic regression analyses. Covariates included
      age, gender, obesity severity, tumour size and tumour complexity. RESULTS: Of 237
      obese patients undergoing partial nephrectomy, 25% underwent OPN and 75%
      underwent RAPN. Apart from larger tumour size in the OPN group (2.8 vs 2.5 cm; P
      = 0.02), there was no significant difference between groups. The rate of intra
      operative blood transfusion (1.1 vs 10%; P = 0.01), the median operating time
      (180 vs 207 min; P < 0.01) and the median ischaemia time (19.5 vs 27 min; P <
      0.01) were all greater for OPN. The LOS was significantly shorter for RAPN (3 vs
      4 days; P < 0.01). While the overall complication rate was higher for OPN (15.8
      vs 31.7%; P < 0.01), major complications were not significantly different (5.6 vs
      1.7%; P = 0.20). On multivariable analyses, OPN independently predicted longer
      operating time, longer length of stay, and more overall complications.
      CONCLUSIONS: At a high-volume centre, the robot-assisted approach offers less
      blood transfusion, shorter operating time, faster recovery, and fewer peri
      operative complications compared with the open approach in obese patients
      undergoing partial nephrectomy for small renal masses. In this setting, RAPN may
      be a preferable treatment option.

PMID- 27699970
TI  - Asymptomatic cryptococcal antigen prevalence detected by lateral flow assay in
      hospitalised HIV-infected patients in Sao Paulo, Brazil.
AB  - OBJECTIVE: To determine the prevalence of asymptomatic cryptococcal antigen
      (CRAG) using lateral flow assay (LFA) in hospitalised HIV-infected patients with
      CD4 counts <200 cells/MUl. METHODS: Hospitalised HIV-infected patients were
      prospectively recruited at Instituto de Infectologia Emilio Ribas, a tertiary
      referral hospital to HIV-infected patients serving the Sao Paulo State, Brazil.
      All patients were >18 years old without prior cryptococcal meningitis, without
      clinical suspicion of cryptococcal meningitis, regardless of antiretroviral (ART)
      status, and with CD4 counts <200 cells/MUl. Serum CRAG was tested by LFA in all
      patients, and whole blood CRAG was tested by LFA in positive cases. RESULTS: We
      enrolled 163 participants of whom 61% were men. The duration of HIV diagnosis was
      a median of 8 (range, 1-29) years. 26% were antiretroviral (ART)-naive, and 74%
      were ART-experienced. The median CD4 cell count was 25 (range, 1-192) cells/MUl.
      Five patients (3.1%; 95%CI, 1.0-7.0%) were asymptomatic CRAG-positive. Positive
      results cases were cross-verified by performing LFA in whole blood. CONCLUSIONS:
      3.1% of HIV-infected inpatients with CD4 <200 cells/MUl without symptomatic
      meningitis had cryptococcal antigenemia in Sao Paulo, suggesting that routine
      CRAG screening may be beneficial in similar settings in South America. Our study
      reveals another targeted population for CRAG screening: hospitalised HIV-infected
      patients with CD4 <200 cells/MUl, regardless of ART status. Whole blood CRAG LFA
      screening seems to be a simple strategy to prevention of symptomatic meningitis.

PMID- 27699974
TI  - IMAGING DIAGNOSIS-ULTRASONOGRAPHIC APPEARANCE OF SKELETAL MUSCLE METASTASES IN A
      DOG WITH HEMANGIOSARCOMA.
AB  - A 13-year-old spayed female German shepherd dog was presented for acute onset of
      lethargy, anorexia, and disseminated erythematous skin lesions. Thoracic
      radiographs and abdominal ultrasonographic findings were consistent with
      metastatic hemangiosarcoma. Multiple, ill-defined, irregularly shaped hypoechoic
      nodules were also detected within the thoracic and abdominal wall.
      Hemangiosarcoma metastases to the skeletal muscle were confirmed based on
      histopathological examination. Multivisceral involvement was also confirmed by
      necropsy. Metastatic neoplasia should be considered as a differential diagnosis
      for dogs with ill-defined, irregular, hypoechoic, intramuscular nodules.

PMID- 27699975
TI  - Targeted Nanoparticle Thermometry: A Method to Measure Local Temperature at the
      Nanoscale Point Where Water Vapor Nucleation Occurs.
AB  - An optical nanothermometer technique based on laser trapping, moving and targeted
      attaching an erbium oxide nanoparticle cluster is developed to measure the local
      temperature. The authors apply this new nanoscale temperature measuring technique
      (limited by the size of the nanoparticles) to measure the temperature of vapor
      nucleation in water. Vapor nucleation is observed after superheating water above
      the boiling point for degassed and nondegassed water. The average nucleation
      temperature for water without gas is 560 K but this temperature is lowered by 100
      K when gas is introduced into the water. The authors are able to measure the
      temperature inside the bubble during bubble formation and find that the
      temperature inside the bubble spikes to over 1000 K because the heat source
      (optically-heated nanorods) is no longer connected to liquid water and heat
      dissipation is greatly reduced.

PMID- 27699976
TI  - New surgical treatments for faecal incontinence.

PMID- 27699981
TI  - Research progress of long noncoding RNA in China.
AB  - RNA is essential for all kingdoms of life and exerts important functions beyond
      transferring genetic information from DNA to protein. With the advent of the
      state-of-the-art deep sequencing technology, a large portion of noncoding
      transcripts in eukaryotic genomes has been broadly identified. Among them, long
      noncoding RNAs (lncRNAs) have been emerged as a new class of RNA molecules that
      have regulatory potential in a variety of physiological and pathological
      processes. Here we summarize recent research progresses that have been made by
      scientists in China on lncRNAs, including their biogenesis, functional
      implication and the underlying mechanism of action at the current stage. (c) 2016
      IUBMB Life, 68(11):887-893, 2016.

PMID- 27699983
TI  - Sonifying science: listening to cancer.
AB  - As a long-time scholar of science and art practices, I look particularly at the
      role of tools and instruments which make these practices possible. I note that
      science, historically, has favoured visualist imaging, but art, particularly in
      performance modes, often uses acoustic imaging. Early modern science was
      dominantly optical in instrumentation, but uses of optics often preceded science
      use in early modern times. In late modern times, much more complex
      instrumentation often originated in the sciences, but artists frequently adapted
      to acoustic practices. Sonifying science, from imaging space phenomena to medical
      phenomena, is traced here, focusing upon medical sonification in detecting
      cancers.

PMID- 27699984
TI  - Two sides of a coin: host-plant synchrony fitness trade-offs in the population
      dynamics of the western spruce budworm.
AB  - Conifer-feeding budworms emerge from overwintering sites as small larvae in early
      spring, several days before budburst, and mine old needles. These early-emerging
      larvae suffer considerable mortality during this foraging period as they disperse
      in search of available, current-year buds. Once buds flush, surviving budworms
      construct feeding shelters and must complete maturation before fresh host foliage
      senesces and lignifies later in the summer. Late-developing larvae suffer greater
      mortality and survivors have lower fecundity when feeding on older foliage. Thus,
      there is a seasonal trade-off in fitness associated with host synchrony: early
      emerging budworms have a greater risk of mortality during spring dispersal but
      gain better access to the most nutritious foliage, while, on the other hand, late
      emerging larvae incur a lower risk during the initial foraging period but must
      contend with rapidly diminishing resource quality at the end of the feeding
      period. We investigate the balance that results from these early-season and late
      season synchrony fitness trade-offs using the concept of the phenological window.
      Parameters associated with the variation in the phenological window are used to
      estimate generational fitness as a function of host-plant synchrony. Because
      defoliation modifies these relationships, it is also included in the analysis. We
      show that fitness trade-offs characterizing the phenological window result in a
      robust synchrony relationship between budworm and host plant over a wide
      geographic range in southern British Columbia, Canada.

PMID- 27699985
TI  - Ethnicity affects IVF outcome world-wide with no clear explanation.

PMID- 27699982
TI  - Unsung renal receptors: orphan G-protein-coupled receptors play essential roles
      in renal development and homeostasis.
AB  - Recent studies have shown that orphan GPCRs of the GPR family are utilized as
      specialized chemosensors in various tissues to detect metabolites, and in turn to
      activate downstream pathways which regulate systemic homeostasis. These studies
      often find that such metabolites are generated by well-known metabolic pathways,
      implying that known metabolites and chemicals may perform novel functions. In
      this review, we summarize recent findings highlighting the role of deorphanized
      GPRs in renal development and function. Understanding the role of these receptors
      is critical in gaining insights into mechanisms that regulate renal function both
      in health and in disease.

PMID- 27699986
TI  - Unresolved attachment and agency in women victims of intimate partner violence: A
      case-control study.
AB  - OBJECTIVES: Women victims of IPV are more likely insecurely attached and have
      experienced childhood abuse, which according to the attachment theory is deeply
      related to disorganized attachment. This case-control study was performed with
      the aim to compare the attachment status and the defensive processing patterns of
      women victims of IPV (cases) with women with no experiences of IPV (controls).
      METHODS: Cases were 16 women with an age range from 26 years to 51 years. The
      control group included 16 women with an age range from 26 years to 59 years.
      Women's states of mind in regard to attachment were evaluated with the Adult
      Attachment Projective Picture System, which allows classifying attachment status
      and defensive mechanisms. RESULTS: Compared with control group, most IPV women
      resulted having an unresolved attachment status and describing characters less
      capable to draw upon internal resources, that is, internalized secure base, and
      less capable to act than controls. Women victims of IPV used significantly more
      words referring danger and failed protection than controls. CONCLUSIONS: The
      results evidenced the strong effectiveness of the AAP on analysing the
      psychological attitudes of women victims of IPV. The dramatic events lived by the
      women victims of IPV are so dominant in their minds that they invade their
      stories. This could represent a clue of emotional dysregulation. PRACTITIONER
      POINTS: The use of AAP improves the understanding of the agency of self and of
      the specific levels of trauma experienced by IPV victims, on clarifying their
      frightening/frightened dynamic, typical of the disorganized attachment
      relationship, which undermines their activity of mentalization. The therapist
      will assume the stance of a secure base and then both promoting exploration and
      contrasting impotence, humiliation, and subordination that IPV women have
      experienced. This therapeutic interpersonal context will be functional to reach
      two different but related therapeutic goals: (1) to facilitate the rebuilding of
      agency (through an activation of subject to explore concrete strategies for
      exiting from IPV), (2) to explore attachment-related segregated systems from
      awareness, and to integrate them in memory.

PMID- 27699987
TI  - Growth factor delivery of BMP9 using a novel natural bovine bone graft with
      integrated atelo-collagen type I: Biosynthesis, characterization, and cell
      behavior.
AB  - Within the past years, BMP9 has been characterized as one of the most osteogenic
      bone-inducers among the BMP family, however up until recently, BMP9 has only been
      available through adenovirus transfection experiments (gene therapy) not approved
      for clinical use. The aim of this study was to investigate recombinant rhBMP9
      versus rhBMP2 at 2 concentrations (10 and 100 ng/mL) in combination with 2 bone
      grafts: (1) a natural bone mineral (NBM) without collagen versus (2) a novel NBM
      integrated with atelo-collagen type I (NBM-Col). Scanning electron microscopy
      revealed that while NBM demonstrated a mineralized roughened surface morphology,
      NBM-Col particles contained many more visible collagen fibrils throughout the
      scaffold surface significantly increasing rhBMP adsorption from 8 h to 10 days
      (as quantified by ELISA). Thereafter, ST2 preosteoblasts were used to investigate
      cell attachment, proliferation, and differentiation. While little change was
      observed for cell attachment/proliferation, osteoblast differentiation
      demonstrated a significant increase in alkaline phosphatase (ALP) activity when
      scaffolds were loaded with rhBMP9 when compared to rhBMP2. Furthermore, a 2-3
      fold increase in alizarin red staining, and in mRNA levels of osteoblast
      differentiation markers Runx2, Collagen1alpha2, ALP, and osteocalcin was observed
      when rhBMP9 was combined with NBM-Col when compared to NBM without collagen at
      equivalent doses and when compared to rhBMP2. The results from this study
      demonstrate that (1) the use of rhBMP9 significantly and markedly induced
      osteoblast differentiation when compared to rhBMP2 and (2) the incorporation of
      atelo-collagen type I into NBM bone grafts markedly improved these findings by
      serving as a scaffold capable of improving growth factor adsorption and
      osteoblast behavior. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      105A: 408-418, 2017.

PMID- 27699988
TI  - Spotlights on our sister journals: ChemPhysChem 19/2016.

PMID- 27699989
TI  - Prehospital ketamine use by paramedics in the Australian Capital Territory: A 12
      month retrospective analysis.
AB  - OBJECTIVE: The aim of this study was to describe prehospital use of ketamine by
      ACT Ambulance Service, and frequency of endotracheal intubation. METHODS: This
      was a retrospective study of patients receiving prehospital ketamine between 1
      January and 31 December 2013. Episodes were identified from the prehospital
      electronic patient care records, then linkage to ED records at two receiving
      hospitals. Demographics, dose, indication and occasions of intubation were
      analysed. RESULTS: A total of 163 episodes were identified; 10 of these were
      excluded because of lack of identifying data or missing records (age 1-97 years
      [mean: 43, standard deviation: 21.7], 56% men). Median total dose was 60 mg
      (interquartile range 70; 5-400 mg) in three doses (interquartile range 3; 1-14
      mg). For patients with a weight recorded (63%), median dose was 0.73 mg/kg.
      Indications were analgesia 68%, agitation/combative 25%, rapid sequence
      intubation 5% and others 2%. A total of 26 patients were endotracheally
      intubated, 11 prehospital (seven as an intended rapid sequence intubation and
      four combative patients with return of spontaneous circulation) and 15 in the ED.
      Of ED intubations, 10 were trauma patients and five were drug ingestion related.
      Patients receiving ketamine for combativeness were more likely to be intubated
      than those receiving it for analgesia (25 vs 7.2%; odds ratio: 3.46; 95%
      confidence interval: 1.12, 10.71). In those with a weight recorded, the mg/kg
      dose was not associated with subsequent intubation. CONCLUSIONS: Median dose for
      analgesia was comparable with other studies; dose for sedation was less than
      reported elsewhere. Intubation rate for patients receiving prehospital ketamine
      was 17%. Further study is recommended to assess the ED course of the non
      intubated group of patients, and consideration should be given to non-weight
      based methods of dose selection.

PMID- 27699991
TI  - Medical lines and hospitalized children-Strangulation hazards in plain sight.

PMID- 27699990
TI  - Does the visibility of a congenital anomaly affect maternal-infant attachment
      levels?
AB  - PURPOSE: To determine whether congenital anomaly visibility affects maternal
      infant attachment levels. DESIGN AND METHODS: The study population consisted of
      mothers who had infants with cleft lip/palate or congenital heart anomalies who
      were receiving treatment in a university hospital. The data were collected using
      the Structured Questionnaire Form and the Maternal Attachment Inventory. RESULTS:
      Statistically significant differences in maternal-infant attachment levels were
      observed between infants with cleft lips/palates and healthy infants and between
      infants with congenital heart anomalies and healthy infants. PRACTICE
      IMPLICATIONS: It is important to apply appropriate nursing interventions for
      these mothers during the postpartum period.

PMID- 27699993
TI  - Transient elastography for the diagnosis of liver fibrosis: a systematic review
      of economic evaluations.
AB  - BACKGROUND: Liver biopsy remains the gold standard for the diagnosis of liver
      fibrosis, but its use as a diagnostic tool is limited by its invasive nature and
      high cost. OBJECTIVE: The aim of this study was to systematically review the cost
      effectiveness of transient elastography (TE) with and without controlled
      attenuation parameter (CAP) for the diagnosis of liver fibrosis or steatosis in
      patients with hepatitis B, hepatitis C, alcoholic liver disease and non-alcoholic
      fatty liver disease. METHODS: An economic literature search was performed.
      Eligibility criteria included systematic reviews, health technology assessments
      or economic evaluations of TE compared to liver biopsy and other non-invasive
      tests. After abstract screening, full-text reports of potentially relevant
      articles were assessed in duplicate. The methodological quality of the included
      studies was also appraised. RESULTS: The database search yielded 253 records;
      four cost-effectiveness and four cost-utility studies were included. The
      methodological quality of the included studies varies. High-quality cost
      effectiveness studies not only suggested that TE is less costly but also less
      accurate than liver biopsy. The incremental cost-effectiveness ratio (ICER) of TE
      improves with a greater level of diagnostic accuracy and a higher degree of liver
      fibrosis. High-quality cost-utility studies indicated that TE is a cost-effective
      alternative to biopsy with ICER between $9000 and $14 000 per QALY for patients
      with hepatitis C. We did not find studies that assessed the cost-effectiveness of
      TE with CAP for the diagnosis of liver steatosis. CONCLUSIONS: Transient
      elastography is an economically attractive alternative to liver biopsy and other
      non-invasive diagnostic tests especially for patients with a higher degree of
      liver fibrosis.

PMID- 27699992
TI  - Combined analysis of cross-reacting antibodies anti-beta1AR and anti-B13 in
      advanced stages of Chagas heart disease.
AB  - OBJECTIVE: Autoantibodies cross-reacting with the beta1 adrenergic receptor (anti
      beta1AR and anti-p2beta) and cardiac myosin antigens (anti-B13) have been related
      to the pathogenesis of chronic Chagas heart disease (CCHD). Studies exploring
      their levels in different stages are scarce. We aimed to evaluate the
      relationship of these autoantibodies with the clinical profile of chronic
      patients, especially regarding their classificatory accuracy in severe
      presentation with heart failure. METHODS AND RESULTS: We conducted a cross
      sectional study of 155 T. cruzi-seropositive patients and 26 age- and gender
      matched healthy controls. They were categorised in three stages of CCHD. Serum
      antibodies were measured by specific immunoassays. Symptomatic individuals showed
      increased levels of anti-beta1AR and anti-B13, while anti-p2beta antibodies were
      similar between groups. A composite logistic regression model including anti-B13,
      anti-beta1AR antibody levels and age was able to predict systolic heart failure
      yielding an area under the curve of 83% (sensitivity of 67% and specificity of
      89%). CONCLUSIONS: In our study, anti-beta1AR and anti-B13 antibodies were higher
      in individuals with chronic Chagas heart disease stage III, mainly in those with
      dilated cardiomyopathy associated with systolic heart failure. Logistic
      regression analysis showed that both antibodies were good predictors of severe
      CCHD. As well as being involved in disease progression, anti-beta1AR and anti-B13
      antibodies may be used as a serum marker of poor prognosis in terms of heart
      compromise.

PMID- 27699994
TI  - Degradation of alkanethiol self-assembled monolayers in mesenchymal stem cell
      culture.
AB  - Alkanethiol self-assembled monolayers (SAMs) have been used extensively in
      studying the role of surface functionality and geometry on stem cell
      differentiation; however, the effects of stem cell culture conditions on SAM
      stability over time are not well understood. In this work, we examined the
      physical and chemical changes occurring on gold (Au)-SAM surfaces over time as a
      function of Au thickness. Within a narrow range of thicknesses (4, 8, and 10 nm),
      we observed significant differences in temporal SAM stability for a commonly
      utilized, hydrophilic, protein and cell repulsive oligo(ethylene) glycol
      alkanethiol (HS-(CH2 )11 (O(CH2 )2 )6 OH) SAM and the hydrophobic, protein
      adhesive hexadecanethiol (SH-(CH2 )15 CH3 ) SAM. Within both acellular and stem
      cell culture conditions, 8 nm Au resulted in the most stable SAMs (~7 days). The
      4 and 10 nm Au SAMs exhibited loss in stability following 5 days at varying
      degradation rates, showing 4 nm Au to be the least stable. Migration of human
      mesenchymal stem cells seeded on SAM surfaces showed that SAM degradation rates
      in acellular conditions were directly correlated with the cellular migration
      behavior. Findings of this study can be used to develop SAM surfaces with
      controlled degradation rates for applications in stem cell engineering and
      regenerative medicine. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 105A: 464-474, 2017.

PMID- 27699995
TI  - Synthesis of ZnSe and ZnSe:Cu quantum dots by a room temperature photochemical
      (UV-assisted) approach using Na2 SeO3 as Se source and investigating optical
      properties.
AB  - In this study, ZnSe and ZnSe:Cu quantum dots (QDs) were synthesized using Na2
      SeO3 as the Se source by a rapid and room temperature photochemical (UV-assisted)
      approach. Thioglycolic acid (TGA) was employed as the capping agent and UV
      illumination activated the chemical reactions. Synthesized QDs were successfully
      characterized using X-ray diffraction (XRD), transmission electron microscopy
      (TEM), photoluminescence (PL) and UV-visible (UV-vis) spectroscopy, Fourier
      transform-infrared (FT-IR), and energy dispersive X-ray spectroscopy (EDX). XRD
      analysis demonstrated the cubic zinc blend phase QDs. TEM images indicated that
      round-shaped particles were formed, most of which had a diameter of about 4 nm.
      The band gap of the ZnSe QDs was higher than that for ZnSe in bulk. PL spectra
      indicated an emission with three peaks related to the excitonic, surface trap
      states and deep level (DL) states. The band gap and QD emission were tunable only
      by UV illumination time during synthesis. ZnSe:Cu showed green emission due to
      transition of electrons from the Conduction band (CB) or surface trap states to
      the 2 T2 acceptor levels of Cu2+ . The emission was increased by increasing the
      Cu2+ ion concentration, such that the optimal value of PL intensity was obtained
      for the nominal mole ratio of Cu:Zn 1.5%.

PMID- 27699996
TI  - Evaluating the Usefulness of Compulsory Licensing in Developing Countries: A
      Comparative Study of Thai and Brazilian Experiences Regarding Access to Aids
      Treatments.
AB  - While compulsory licensing (CL) is described in the TRIPS agreement as
      flexibility to protect public health by improving access to medicines in
      developing countries, a recent literature contends adversely that CL may harm
      public health. Therefore, this article intends to evaluate the usefulness of CL
      in the South through the prism of obligations and goals entrusted to patent
      holders (the effective and non-abusive exploitation of patents in order to
      achieve industrial and health developments) and in light of experiences in
      Thailand and Brazil regarding access to antiretroviral drugs. In this way, it
      shows that the obligations assigned to patent holders were better served by the
      recipients of CL and brought significant health and industrial benefits in the
      two high middle-income countries. In particular, CL allowed the scaling-up of
      free and universal access to antiretroviral drugs by assuring the financial
      sustainability of these public health programs endangered by monopolistic
      practices from patent holders.

PMID- 27699997
TI  - Comparison of postpartum haemorrhage guidelines: discrepancies underline our lack
      of knowledge.

PMID- 27699998
TI  - Assessment of quality of life, anxiety, socio-economic factors and caries
      experience in Brazilian children with overweight and obesity.
AB  - PURPOSE: This study evaluated the association between excess weight and quality
      of life (QoL), symptoms of anxiety, caries experience and socio-economic factors
      in a representative sample of 8- to 10-year-old children from three public
      schools of Piracicaba (SP, Brazil). MATERIALS AND METHODS: The Autoquestionnaire
      Qualite de Vie Enfant Image was applied to explore family and social relations,
      activities, health, body functions and separation domains, and, by means of the
      Multidimensional Anxiety Scale for Children, symptoms of anxiety were screened.
      Clinical examination was performed using DMFT/dmft indexes to assess oral health
      and caries experience. Medical and nutritional history, parents' schooling,
      monthly income and ownership of household goods and services were also evaluated.
      RESULTS: Of the 313 subjects included, four subjects were underweight, 188 normal
      weight, 67 overweight and 54 presented obesity (38.7% with excess weight).
      Measures of QoL, anxiety scores and caries experience did not differ between
      groups. The regression model showed a significant association between excess
      weight and the ownership of household goods and services (OR = 5.4/CI = 1.6
      18.3). CONCLUSIONS: High prevalence of excess weight was observed among
      prepubertal children, emphasizing the need for continued health programmes to
      limit risk factors for obesity. QoL, anxiety scores and caries experience did not
      differ between subjects with different body weights, although children from
      public schools with higher ownership of goods and services were more likely to
      present excess weight.

PMID- 27699999
TI  - Outpatient administration of BEAM conditioning prior to autologous stem cell
      transplantation for lymphoma is safe, feasible, and cost-effective.
AB  - High-dose BEAM chemotherapy (BCNU, etoposide, Ara-C, and melphalan) followed by
      autologous hematopoietic stem cell transplantation is frequently used as
      consolidative therapy for patients with recurrent or refractory Hodgkin or non
      Hodgkin lymphoma. The BEAM regimen has traditionally been administered over 6
      days in the hospital, with patients remaining hospitalized until hematologic
      recovery and clinical stability. In an effort to reduce the length of
      hospitalization for these patients, our institution has transitioned from
      inpatient (IP) to outpatient (OP) administration of BEAM conditioning. Here, we
      report the results of an analysis of the feasibility, cost, complications, and
      outcomes for the initial group of patients who received OP BEAM compared to a
      prior cohort of patients who received IP BEAM. Patient and disease
      characteristics were comparable for the two cohorts, as were engraftment
      kinetics. Length of hospital stay was reduced by 6 days for the OP cohort (P <
      0.001), resulting in a cost savings of more than $17,000 per patient. Fewer
      complications occurred in the OP cohort, including severe enteritis (P = 0.01),
      organ toxicities (P = 0.01), and infections (P = 0.04). Overall survival rate up
      to 3 years posttransplant was better for the OP cohort (P = 0.02), likely due to
      differences in posttransplant therapies. We conclude that OP administration of
      BEAM conditioning is safe and may offer significant advantages, including
      decreased length of hospitalization, reduced costs, decreased risks for severe
      toxicities and infectious complications, and likely improvement in patient
      satisfaction and quality of life.

PMID- 27700000
TI  - Identification and Characterization of microRNAs Associated With Human beta-Cell
      Loss in a Mouse Model.
AB  - Currently there is no effective approach for monitoring early beta-cell loss
      during islet graft rejection following human islet transplantation (HIT). Due to
      ethical and technical constraints, it is difficult to directly study biomarkers
      of islet destruction in humans. Here, we established a humanized mouse model with
      induced human beta-cell death using adoptive lymphocyte transfer (ALT). Human
      islet grafts of ALT-treated mice had perigraft lymphocyte infiltration, fewer
      insulin+ beta cells, and increased beta-cell apoptosis. Islet-specific miR-375
      was used to validate our model, and expression of miR-375 was significantly
      decreased in the grafts and increased in the circulation of ALT-treated mice
      before hyperglycemia. A NanoString expression assay was further used to profile
      800 human miRNAs in the human islet grafts, and the results were validated using
      quantitative real-time polymerase chain reaction. We found that miR-4454 and miR
      199a-5p were decreased in the human islet grafts following ALT and increased in
      the circulation prior to hyperglycemia. These data demonstrate that our in vivo
      model of induced human beta-cell destruction is a robust method for identifying
      and characterizing circulating biomarkers, and suggest that miR-4454 and miR-199a
      5p can serve as novel biomarkers associated with early human beta-cell loss
      following HIT.

PMID- 27700002
TI  - IEPA 10th International Conference on Early Intervention in Mental Health -
      "Looking Back, Moving Forward" Milan, Italy, 20th - 22nd October 2016.

PMID- 27700001
TI  - Hepatitis C in nonobese nondiabetic patients: Insulin resistance and the
      metabolic syndrome make a difference.

PMID- 27700003
TI  - Strigolactones and parasitic weed management 50 years after the discovery of the
      first natural strigolactone strigol: status and outlook.

PMID- 27700004
TI  - Purification and identification of corn peptides that facilitate alcohol
      metabolism by semi-preparative high-performance liquid chromatography and nano
      liquid chromatography with electrospray ionization tandem mass spectrometry.
AB  - In this study, peptides that facilitate alcohol metabolism were purified and
      identified from corn protein hydrolysates. The ultra-filtered fraction with a
      molecular weight < 3 kDa (F3) potential activity was separated into six fractions
      (F3-H1-F3-H6) by semi-preparative high-performance liquid chromatography. Among
      the resultant six fractions, F3-H4 and F3-H5 exhibited the highest ability to
      eliminate alcohol in vivo. A total of 16 peptides with strong signal values were
      identified from F3-H4 and F3-H5 fractions by nano liquid chromatography coupled
      with electrospray ionization tandem mass spectrometry. Several identified
      peptides were then selected and synthesized to determine their potential to
      facilitate alcohol metabolism. We found that Leu-Leu and Pro-Phe were the key
      structure units in Gln-Leu-Leu-Pro-Phe responsible for this peptide's ability to
      facilitate alcohol metabolism. However, the role of Leu-Leu and Pro-Phe may be
      affected by peptide chain length and hydrophobic properties. Our results have
      thus provided some insight into the study of the structure-activity relationships
      of corn peptides.

PMID- 27700006
TI  - Flight or fright: training in a high-stakes zone.

PMID- 27700005
TI  - High-flow oxygen in patients undergoing procedural sedation in the emergency
      department: A retrospective chart review.
AB  - OBJECTIVE: Hypoxia is a recognised complication of procedural sedation. This
      study sought to determine whether there was an association between the use of
      high-flow oxygen delivery by a non-rebreather (NRB) mask during ED procedural
      sedation and decreased rates of hypoxia when compared with alternative
      oxygenation methods. METHODS: Records of all procedural sedations performed over
      a 12 month period in an Australian tertiary ED were reviewed retrospectively. The
      primary outcome was whether recorded oxygen saturations fell below 90%. Specifics
      of the oxygen delivery method were noted and data collected included sex, age,
      indication for sedation, drugs and doses administered, time of day sedation was
      commenced and staff grade of sedationist. RESULTS: A total of 755 procedural
      sedations were reviewed. Two hundred and five (27.1%) patients were administered
      oxygen via NRB mask from the outset of their sedation. NRB administration was
      associated with a statistically significant decreased rate of hypoxia (1/205
      patients vs 23/550 [odds ratio: 0.112; 95% confidence interval: 0.003-0.0702]; P
      = 0.0090). This association remained statistically significant when adjusted for
      confounders. CONCLUSIONS: This study demonstrates an association with a
      statistically significant reduction in hypoxia when high-flow oxygen via NRB mask
      is administered during emergency procedural sedation. This intervention is
      simple, safe and inexpensive, and we would advocate that it be evaluated further
      in prospective trials.

PMID- 27700007
TI  - What the Evolution of Female Orgasm Teaches Us.

PMID- 27700009
TI  - Fluid manipulation on the micro-scale: Basics of fluid behavior in microfluidics.
AB  - Fluid manipulation on the micro-scale (microfluidics) is bringing new potential
      applications in a number of fields, including chemistry, biology and medicine. At
      sub-millimeter channel scale, some phenomena, unimportant at the macroscale,
      become an important force to consider when designing a microfluidics system. For
      example, the decrease in fluid mass causes the effects of viscosity to overcome
      the influence of inertia. Turbulent flow cannot be achieved at any realistic
      fluid velocity, making mixing a challenging task. The only phenomenon capable of
      blending liquids at microscale is diffusion and liquid streams can be flowed side
      by-side for tens of minutes before they completely fuse together. The decrease in
      the channel size also leads to an increased surface-to-volume ratio, which
      increases the importance of surface effects, including adsorption, capillary
      action and surface wetting and/or electric double layer formation with related
      electrokinetic phenomena. While rivers cannot flow uphill, a stream of liquid can
      easily flow up against gravity inside a capillary. Similarly, the formation of
      electric double layer near the charged surface of a micro-channel or capillary
      can be applied for electrokinetic actuating. This review summarizes selected
      physical phenomena related to liquid-based (water solutions) microfluidics as
      described recently.

PMID- 27700008
TI  - Translational Pharmacokinetic/Pharmacodynamic Analysis of MYO-029 Antibody for
      Muscular Dystrophy.
AB  - Suppression of the myostatin (GDF-8) pathway has emerged as an important
      therapeutic paradigm for muscle-wasting disorders. In this study, we conducted a
      translational pharmacokinetic/pharmacodynamic (PK/PD) analysis of MYO-029, an
      anti-myostatin monoclonal antibody, using PK data in mice, rats, monkeys, humans,
      mouse tissue distribution data with 125 I-labeled MYO-029, muscle weight increase
      in SCID mice, and muscle circumference changes in monkeys. This analysis revealed
      significant in vivo potency shift between mice and monkeys (72 nM vs. 1.3 MUM for
      50% effect on quadriceps). Estimated central clearance of MYO-029 (0.38 mL/h/kg)
      in humans was greater than twofold higher than typical IgG mAbs. Peak and trough
      steady-state exposures of MYO-029 in patients at biweekly intravenous doses of 10
      mg/kg MYO-029 are predicted to achieve only 50% and 10% of the maximum effect
      seen in monkeys, respectively. These retrospective analyses results suggest that
      the MYO-029 exposures in this trial had a low probability of producing robust
      efficacy.

PMID- 27700011
TI  - Advanced Biosystems - Now open for submissions!

PMID- 27700010
TI  - The role of trophoblast cell receptor expression in HIV-1 passage across the
      placenta in pre-eclampsia: an observational study.
AB  - OBJECTIVE: To compare expression of markers of HIV and associated receptors (p24,
      CD4, CCR5 and ICAM-2) in placentae and umbilical cords of HIV-associated and pre
      eclamptic pregnancies to elucidate any association between these conditions in
      mother-to-child transmission. DESIGN: Cross-sectional immunohistochemical
      analysis of target receptor expression. SETTING: Laboratory-based study of
      primigravidae attending a district hospital in South Africa. POPULATION OR
      SAMPLE: Retrospectively collected placental tissue (stratified into four groups
      according to HIV status of normotensive and pre-eclamptic participants (n =
      20/group). METHOD: Immunohistochemistry utilising CD4 (1:1), p24 (1:10), CCR5
      (1:80) and ICAM-2 (1:100) antibodies was performed using light microscopy for
      image acquisition and analysis. MAIN OUTCOME MEASURES: Evaluate the expression of
      receptors on syncytiotrophoblast involved in in utero transmission of HIV.
      RESULTS: Syncytiotrophoblast was immunopositive for CD4 and CCR5 antibody with
      greater expression of CCR5 in HIV-positive versus HIV-negative groups (F1,159  =
      6.979, P = 0.009) and normotensive versus pre-eclamptic groups (F1,159  = 8.803,
      P = 0.003). p24 was present in both placentae and umbilical cords of babies that
      were HIV-negative at 6 weeks. ICAM-2 immunostaining was observed in the
      syncytiotrophoblast across study groups and was significantly higher in the HIV
      negative pre-eclamptic group (chi2 (3)  = 45.3; P < 0.001). CONCLUSION:
      Concurrent CD4 and CCR5 receptor expression demonstrates possible in utero viral
      entry routes across the placental barrier. ICAM-2 expression may influence HIV
      passage across the placenta or restoration of risk of pre-eclampsia in HAART
      treated mothers. HIV was found in fetal circulation regardless of antiretroviral
      treatment. Further confirmatory ultrastructural and molecular work is warranted.
      TWEETABLE ABSTRACT: CD4, CCR5 and ICAM-2 on syncytiotrophoblast may facilitate
      HIV infection of passage across the placenta.

PMID- 27700012
TI  - Chemical constituents and quality control of two Dracocephalum species based on
      high-performance liquid chromatographic fingerprints coupled with tandem mass
      spectrometry and chemometrics.
AB  - Two similar Dracocephalum species, namely, Dracocephalum tanguticum Maxim and
      Dracocephalum moldavica L, are commonly used as ethnic medicines in China. Here
      we describe a strategy of combining high-performance liquid chromatography with
      quadrupole time-of-flight mass spectrometry, as well as fingerprints and
      chemometrics for characterization and discrimination of chemical constituents on
      the two herbs. A total of 49 compounds including 33 flavonoids, 5 phenylethanol
      glycosides, 1 coumarin glycoside, 8 organic acids, and 2 other types of compounds
      were unambiguously or tentatively identified from the two Dracocephalum species.
      Among the compounds identified, 26 were characterized for the first time and 4
      compounds, rosmarinic acid (7), salvianolic acid B (10), luteoloside (22),
      diosmetin-7-O-glucoside (28), were inferred as common constituents for the two
      herbs. Flavonoids featured in these two Dracocephalum species while their types
      presented significant differences. Acacetin (45) and acacetin glycosides
      (acatetin-7-O-glucuronide (30), acacetin-7-O-(6"-O-malonyl) glucoside (33),
      buddleoside (34), tilianin (35), and agastachoside (42)) were detected only in D.
      moldavica, which can be used to discriminate two herbal medicines. In addition,
      six characteristic constitutes in D. tanguticum were simultaneously quantified.
      Moreover, the induced chemometrics methods including similarity analysis and
      hierarchical clustering analysis were successfully applied for origin
      discrimination and quality evaluation of D. tanguticum and D. moldavica.

PMID- 27700013
TI  - Biomaterials in siRNA Delivery: A Comprehensive Review.
AB  - With the dearth of effective treatment options for prominent diseases including
      Ebola and cancer, RNA interference (RNAi), a sequence-specific mechanism for
      genetic regulation that can silence nearly any gene, holds the promise of
      unlimited potential in treating illness ever since its discovery in 1999. Given
      the large size, unstable tertiary structure in physiological conditions and
      negative charge of small interfering RNAs (siRNAs), the development of safe and
      effective delivery vehicles is of critical importance in order to drive the
      widespread use of RNAi therapeutics into clinical settings. Immense amounts of
      time and billions of dollars have been devoted into the design of novel and
      diverse delivery strategies, and there are a handful of delivery systems that
      have been successfully translated into clinic. This review provides an
      introduction to the in vivo barriers that need to be addressed by siRNA delivery
      systems. We also discuss the progress up to the most effective and clinically
      advanced siRNA delivery systems including liposomal, polymeric and siRNA
      conjugate delivery systems, as well as their design to overcome the challenges.

PMID- 27700014
TI  - Synthesis and cytotoxic activity of certain benzothiazole derivatives against
      human MCF-7 cancer cell line.
AB  - A new series of benzothiazole has been synthesized as cytotoxic agents. The new
      derivatives were tested for their cytotoxic activity toward the human breast
      cancer MCF-7 cell line against cisplatin as the reference drug. Many derivatives
      revealed good cytotoxic effect, whereas four of them, 4, 5c, 5d, and 6b, were
      more potent than cisplatin, with IC50 values being 8.64, 7.39, 7.56, and 5.15 MUm
      compared to 13.33 MUm of cisplatin. The four derivatives' cytotoxic activity was
      accompanied by regulating free radicals production, by increasing the activity of
      superoxide dismutase and depletion of intracellular reduced glutathione,
      catalase, and glutathione peroxidase activities, accordingly, the high production
      of hydrogen peroxide, nitric oxide, and other free radicals causing tumor cell
      death as monitored by reduction in the synthesis of protein and nucleic acids.
      Most of the tested compounds showed potent to moderate growth inhibitory
      activity; in particular, compound 6b exhibited the highest activity suggesting it
      is a lead compound in cytotoxic activity.

PMID- 27700015
TI  - Outcomes in patients with advanced urothelial carcinoma after discontinuation of
      programmed death (PD)-1 or PD ligand 1 inhibitor therapy.
AB  - OBJECTIVE: To study the subsequent therapy and disease outcomes of patients with
      advanced urothelial carcinoma (UC) after discontinuation of programmed death-1
      (PD-1) or programmed death ligand 1 (PD-L1) inhibitors. PATIENTS AND METHODS: We
      performed a retrospective analysis to examine outcomes and systemic therapy
      administration after PD-1/PD-L1 inhibitor therapy in patients with advanced UC.
      Data on demographics and therapy administered were collected from the
      institutions involved in the study. Univariable Cox regression analyses were
      performed to examine the clinical factors potentially associated with overall
      survival (OS) after PD-1/PD-L1 inhibitor therapy. RESULTS: Data from 62 patients
      were available from four institutions, with capture of subsequent therapy and
      outcomes after checkpoint inhibitor immunotherapy. The median patient age was
      65.5 years and 51 patients (82.3%) were male. The median (range) duration of PD
      1/PD-L1 inhibitor therapy in 55 patients for whom these data were available was
      64 (7-669) days. Of these, 22 patients (35.5%) received post-PD-1/PD-L1 inhibitor
      therapy through a variety of different chemotherapy regimens (n = 16),
      chemobiological combination (n = 1), biological agents (n = 4) and immunotherapy
      (n = 1). The median (range) time from last PD-1/PD-L1 inhibitor therapy to
      subsequent therapy was 58 (14-242) days. The median OS of all patients after
      completion of PD-1/PD-L1 inhibitor therapy was 149 days (95% confidence interval
      [CI]: 75-359). Among those who received some post-PD-1/PD-L1 inhibitor therapy,
      the median OS was 182 days (95% CI: 121-372), and the median time to progression
      was 124 days (95% CI: 61-273) from the start of post-PD-1/PD-L1 therapy. Among
      these 22 patients, the only significant baseline prognostic factor associated
      with OS was performance status. CONCLUSIONS: In this dataset, 35.5% of patients
      with advanced UC received systemic therapy after salvage therapy with PD-1/PD-L1
      inhibitors. Outcomes after subsequent therapy appear similar to those
      historically observed in patients who had not received prior PD-1/PD-L1 inhibitor
      therapy. Further study of patients receiving post-PD-1/PD-L1 inhibitor therapy is
      warranted to identify factors associated with outcomes and potentially
      synergistic sequences.

PMID- 27700018
TI  - A hydrophobic ammonia-oxidizing archaeon of the Nitrosocosmicus clade isolated
      from coal tar-contaminated sediment.
AB  - A wide diversity of ammonia-oxidizing archaea (AOA) within the phylum
      Thaumarchaeota exists and plays a key role in the N cycle in a variety of
      habitats. In this study, we isolated and characterized an ammonia-oxidizing
      archaeon, strain MY3, from a coal tar-contaminated sediment. Phylogenetically,
      strain MY3 falls in clade 'Nitrosocosmicus' of the thaumarchaeotal group I.1b.
      The cells of strain MY3 are large 'walnut-like' cocci, divide by binary fission
      along a central cingulum, and form aggregates. Strain MY3 is mesophilic and
      neutrophilic. An assay of 13 C-bicarbonate incorporation into archaeal membrane
      lipids indicated that strain MY3 is capable of autotrophy. In contrast to some
      other AOA, TCA cycle intermediates, i.e. pruvate, oxaloacetate and alpha
      ketoglutarate, did not affect the growth rates and yields of strain MY3. The
      attachment of cells of strain MY3 to XAD-7 hydrophobic beads and to the adsorbent
      vermiculite demonstrated the potential of strain MY3 to form biofilms. The cell
      surface was confirmed to be hydrophobic by the extraction of strain MY3 from an
      aqueous medium with p-xylene. Our finding of a strong potential for surface
      attachment by strain MY3 may reflect an adaptation to the selective pressures in
      hydrophobic terrestrial environments.

PMID- 27700017
TI  - Mitochondrial pathway and endoplasmic reticulum stress participate in the
      photosensitizing effectiveness of AE-PDT in MG63 cells.
AB  - Photodynamic therapy (PDT) is a promising treatment in cancer therapy, with a
      photosensitizer activated by visible light. Aloe-emodin (AE) is a promising
      photosensitive agent. In this study, the photosensitizing effects and possible
      mechanisms of AE-PDT in MG63 cells were evaluated. The efficiency of AE-PDT was
      analyzed by MTT assay. The mode of cell death was investigated by Hoechst 33,342
      staining and flow cytometer. The intracellular distribution of AE was detected
      with confocal microscopy. The formation of reactive oxygen species (ROS) was
      detected by DCFH-DA. The mitochondrial membrane potential (MMP) was measured by
      Rhodamine 123. The expression of proteins including cytochrome c, caspase-3, -9,
      and -12, CHOP and GRP78 was detected by western blot. Apoptosis is the primary
      mode of cell death in our study, which occurs in a manner of depending on AE
      concentration and irradiation dose. Confocal microscopy showed that AE was
      primarily localized on the mitochondria and endoplasmic reticulum (ER) of MG63
      cells. AE-PDT resulted in rapid increases of intracellular ROS production, which
      reached a peak at 2 h, followed by declining of mitochondrial membrane potential,
      releasing of cytochrome c from mitochondria into the cytoplasm, and up-regulation
      of caspase-3, -9, and -12, CHOP and GRP78. These results suggest that death of
      MG63 cells induced by AE-PDT is triggered by ROS. Meanwhile, Mitochondria and ER
      serve as the subcellular targets, which are responsible for AE-PDT-induced death
      of MG63 cells.

PMID- 27700021
TI  - Selective Release of Hydrophobic and Hydrophilic Cargos from Multi-Stimuli
      Responsive Nanogels.
AB  - Highly stable multi-stimuli-responsive nanogels for selective release of
      simultaneously encapsulated hydrophobic and hydrophilic cargos in a
      spatiotemporally controlled manner are demonstrated here. The nanogel is composed
      of hydrophilic pH- and thermoresponsive poly(2-(dimethylamino)ethyl methacrylate)
      (PDMAEMA) and hydrophobic photocleavable o-nitrobenzyl (ONB) linkage. The
      hydrophobic cargos were noncovalently encapsulated into lipophilic interiors of
      the nanogels, while the hydrophilic cargos were chemically linked to the nanogel
      precursor polymer PDMAEMA through a redox-cleavable disulfide junction. For these
      dual-loaded nanogels, hydrophobic cargos can be released in response to
      temperature, pH, and UV light, while the hydrophilic cargos can be released in
      response to redox reagent. The stimuli-selective release of hydrophobic and
      hydrophilic cargos affords the system with great potential applications in
      combination chemotherapy, tissue engineering, anticorrosion, and smart
      nanoreactors.

PMID- 27700020
TI  - One-Step Route to Iron Oxide Hollow Nanocuboids by Cluster Condensation:
      Implementation in Water Remediation Technology.
AB  - The fabrication procedure of hollow iron oxide nanoparticles with a large surface
      to volume ratio by a single-step gas condensation process at ambient temperature
      is presented. Fe clusters formed during the sputtering process are progressively
      transformed into hollow cuboids with oxide shells by the Kirkendall mechanism at
      the expense of oxygen captured inside the deposition chamber. TEM and Raman
      spectroscopy techniques point to magnetite as the main component of the
      nanocuboids; however, the magnetic behavior exhibited by the samples suggests the
      presence of FeO as well. In addition, these particles showed strong stability
      after several months of exposure to ambient conditions, making them of potential
      interest in diverse technological applications. In particular, these hierarchical
      hollow particles turned out to be very efficient for both As(III) and As(V)
      absorption (326 and 190 mg/g, respectively), thus making them of strong interest
      for drinking water remediation.

PMID- 27700016
TI  - Body mass index, weight change, and risk of second primary breast cancer in the
      WECARE study: influence of estrogen receptor status of the first breast cancer.
AB  - Studies examining the relationship between body mass index (BMI) and risk of
      contralateral breast cancer (CBC) have reported mixed findings. We previously
      showed that obese postmenopausal women with estrogen receptor (ER)-negative
      breast cancer have a fivefold higher risk of CBC compared with normal weight
      women. In the current analysis, we reexamined this relationship in the expanded
      Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study, focusing
      on the impact of menopausal status and ER status of the first breast cancer. The
      WECARE Study is a population-based case-control study of young women with CBC
      (cases, N = 1386) and with unilateral breast cancer (controls, N = 2045). Rate
      ratios (RR) and 95% confidence intervals (CI) were calculated to assess the
      relationship between BMI and risk of CBC stratified by menopausal and ER status.
      Positive associations with obesity and weight gain were limited to women who
      became postmenopausal following their first primary breast cancer. Among those
      with an ER-negative first breast cancer, obesity (vs. normal weight) at first
      diagnosis was associated with an increased risk of CBC (RR = 1.9, 95% CI: 1.02,
      3.4). Also, weight gain of >=10 kg after first diagnosis was associated with an
      almost twofold increased risk of CBC (RR = 1.9, 95% CI: 0.99, 3.8). These results
      suggest that women with an ER-negative first primary cancer who are obese at
      first primary diagnosis or who experience a large weight gain afterward may
      benefit from heightened surveillance. Future studies are needed to address the
      impact of weight loss interventions on risk of CBC.

PMID- 27700022
TI  - Highly Integrated Polysulfone/Polyacrylonitrile/Polyamide-6 Air Filter for
      Multilevel Physical Sieving Airborne Particles.
AB  - Rational structural design involving controlled pore size, high porosity, and
      particle-targeted function is critical to the realization of highly efficient air
      filters, and the filter with absolute particle-screen ability has significant
      technological implications for applications including individual protection,
      industrial security, and environmental governance; however, it remains an ongoing
      challenge. In this study, we first report a facile and scalable strategy to
      fabricate the highly integrated polysulfone/polyacrylonitrile/polyamide-6
      (PSU/PAN/PA-6) air filter for multilevel physical sieving airborne particles via
      sequential electrospinning. Our strategy causes the PSU microfiber (diameter of
      ~1 MUm) layer, PAN nanofiber (diameter of ~200 nm) layer, and PA-6 nanonets
      (diameter of ~20 nm) layer to orderly assemble into the integrated filter with
      gradually varied pore structures and high porosity and thus enables the filter to
      work efficiently by employing different layers to cut off penetration of
      particles with a certain size that exceeds the designed threshold level. By
      virtue of its elaborate gradient structure, robust hydrophobicity (WCA of ~130
      degrees ), and superior mechanical property (5.6 MPa), our PSU/PAN/PA-6 filter
      even can filtrate the 300 nm particles with a high removal efficiency of 99.992%
      and a low pressure drop of 118 Pa in the way of physical sieving manner, which
      completely gets rid of the negative impact from high airflow speed, electret
      failure, and high humidity. It is expected that our highly integrated filter has
      wider applications for filtration and separation and design of 3D functional
      structure in the future.

PMID- 27700024
TI  - Gel Polymer Electrolytes Containing Anion-Trapping Boron Moieties for Lithium-Ion
      Battery Applications.
AB  - Gel polymer electrolytes (GPEs) based on semi-interpenetrating polymer network
      (IPN) structure for lithium-ion batteries were prepared by mixing boron
      containing crosslinker (BC) composed of ion-conducting ethylene oxide (EO)
      chains, crosslinkable methacrylate group, and anion-trapping boron moiety with
      poly(vinylidene fluoride) (PVDF) followed by ultraviolet light-induced curing
      process. Various physical and electrochemical properties of the GPEs were
      systematically investigated by varying the EO chain length and boron content.
      Dimensional stability at high temperature without thermal shrinkage, if any, was
      observed due to the presence of thermally stable PVDF in the GPEs. GPE having 80
      wt% of BC and 20 wt% of PVDF exhibited an ionic conductivity of 4.2 mS cm-1 at 30
      oC which is one order of magnitude larger than that of the liquid electrolyte
      system containing the commercial Celgard separator (0.4 mS cm-1) owing to the
      facile electrolyte uptake ability of EO chain and anion-trapping ability of boron
      moiety. As a result, lithium-ion battery cell prepared using the GPE with BC
      showed an excellent cycle performance at 1.0 C maintaining 87 % of capacity
      during 100 cycles.

PMID- 27700023
TI  - Counter Electrode Impact on Quantum Dot Solar Cell Efficiencies.
AB  - The counter electrode (CE), despite being as relevant as the photoanode in a
      quantum dot solar cell (QDSC), has hardly received the scientific attention it
      deserves. In this study, nine CEs (single-walled carbon nanotubes (SWCNTs),
      tungsten oxide (WO3), poly(3,4-ethylenedioxythiophene) (PEDOT), copper sulfide
      (Cu2S), candle soot, functionalized multiwalled carbon nanotubes (F-MWCNTs),
      reduced tungsten oxide (WO3-x), carbon fabric (C-Fabric), and C-Fabric/WO3-x)
      were prepared by using low-cost components and facile procedures. QDSCs were
      fabricated with a TiO2/CdS film which served as a common photoanode for all CEs.
      The power conversion efficiencies (PCEs) were 2.02, 2.1, 2.79, 2.88, 2.95, 3.78,
      3.66, 3.96, and 4.6%, respectively, and the incident photon to current conversion
      efficiency response was also found to complement the PCE response. Among all CEs
      employed here, C-Fabric/WO3-x outperforms all the other CEs, for the synergy
      between C-Fabric and WO3-x comes to the fore during cell operation. The low sheet
      resistance of C-Fabric and its high surface area due to the meshlike morphology
      enables high WO3-x loading during electrodeposition, and the good
      electrocatalytic activity of WO3-x, the very low overpotential, and its high
      electrical conductivity that facilitate electron transfer to the electrolyte are
      responsible for the superior PCE. WO3-based electrodes have not been used until
      date in QDSCs; the ease of fabrication of WO3 films and their good chemical
      stability and scalability also favor their application to QDSCs. Futuristic
      possibilities for other novel composite CEs are also discussed. We anticipate
      this study to be useful for a well-rounded development of high-performance QDSCs.

PMID- 27700025
TI  - Conjugated or Broken: The Introduction of Isolation Spacer ahead of the Anchoring
      Moiety and the Improved Device Performance.
AB  - Acceptors in traditional dyes are generally designed closed to TiO2 substrate to
      form a strong electronic coupling with each other (e.g., cyanoacrylic acid) to
      enhance the electron injection for the high performance of the corresponding
      solar cells. However, some newly developed dyes with chromophores or main
      acceptors isolated from anchoring groups also exhibit comparable or even higher
      performances. To investigate the relatively untouched electronic coupling effect
      in dye-sensitized solar cells, a relatively precise method is proposed in which
      the strength is adjusted gradually by changing isolation spacers between main
      acceptors and anchoring groups to partially control the electronic interaction.
      After an analysis of 3 different groups of 11 sensitizers, it is inferred that
      the electronic coupling should be kept at a suitable level to balance the
      electron injection and recombination. Based on a reference dye LI-81 possessing a
      cyanoacrylic acid as acceptor and anchoring group, both photocurrent and
      photovoltage are synergistically improved after the properties of isolation
      spacers were changed through the adjustment of the length, steric hindrance, and
      push-pull electronic characteristic. Accordingly, the rationally designed dye LI
      87 with an isolation spacer of thiophene ethylene gives an efficiency of 8.54%
      and further improved to 9.07% in the presence of CDCA, showing a new way to
      develop efficient sensitizers.

PMID- 27700026
TI  - Exploring Lithium-Cobalt-Nickel-Oxide Spinel Electrodes for >=3.5 V Li-Ion Cells.
AB  - Recent reports have indicated that a manganese oxide spinel component, when
      embedded in a relatively small concentration in layered xLi2MnO3?(1-x)LiMO2
      (M=Ni, Mn, Co) electrode systems, can act as a stabilizer that increases their
      capacity, rate capability, cycle life, and first-cycle efficiency. These findings
      prompted us to explore the possibility of exploiting lithiated cobalt oxide
      spinel stabilizers by taking advantage of (1) the low mobility of cobalt ions
      relative to manganese and nickel ions in close-packed oxides and (2) their higher
      potential (~3.6 V vs. Li0) relative to manganese oxide spinels (~2.9 V vs. Li0)
      for the spinel-to-lithiated spinel electrochemical reaction. In particular, we
      have revisited the structural and electrochemical properties of lithiated spinels
      in the LiCo1-xNixO2 (0<=x<=0.2) system, first reported almost 25 years ago, by
      means of high-resolution (synchrotron) X-ray diffraction, transmission electron
      microscopy, nuclear magnetic resonance spectroscopy, electrochemical cell tests,
      and theoretical calculations. The results provide a deeper understanding of the
      complexity of intergrown layered/lithiated spinel LiCo1-xNixO2 structures, when
      prepared in air between 400 and 800  degrees C, and the impact of structural
      variations on their electrochemical behavior. These structures, when used in low
      concentration, offer the possibility of improving the cycling stability, energy,
      and power of high energy (>=3.5 V) lithium-ion cells.

PMID- 27700027
TI  - Mesoporous SnO2 Nanostructures of Ultrahigh Surface Areas by Novel Anodization.
AB  - Here we report a novel type of hierarchical mesoporous SnO2 nanostructures
      fabricated by a facile anodization method in a novel electrolyte system (an
      ethylene glycol solution of H2C2O4/NH4F) followed by thermal annealing at a low
      temperature. The SnO2 nanostructures thus obtained feature highly porous
      nanosheets with mesoporous pores well below 10 nm, enabling a remarkably high
      surface area of 202.8 m2/g which represents one of the highest values reported to
      date on SnO2 nanostructures. The formation of this novel type of SnO2
      nanostructures is ascribed to an interesting self-assembly mechanism of the
      anodic tin oxalate, which was found to be heavily impacted by the anodization
      voltage and water content in the electrolyte. The electrochemical measurements of
      the mesoporous SnO2 nanostructures indicate their promising applications as
      lithium-ion battery and supercapacitor electrode materials.

PMID- 27700028
TI  - Orientation Control of Block Copolymers Using Surface Active, Phase-Preferential
      Additives.
AB  - Orientation control of thin film nanostructures derived from block copolymers
      (BCPs) are of great interest for various emerging technologies like separation
      membranes, nanopatterning, and energy storage. While many BCP compositions have
      been developed for these applications, perpendicular orientation of these BCP
      domains is still very challenging to achieve. Herein we report on a new,
      integration-friendly approach in which small amounts of a phase-preferential,
      surface active polymer (SAP) was used as an additive to a polycarbonate
      containing BCP formulation to obtain perpendicularly oriented domains with 19 nm
      natural periodicity upon thermal annealing. In this work, the vertically oriented
      BCP domains were used to demonstrate next generation patterning applications for
      advanced semiconductor nodes. Furthermore, these domains were used to demonstrate
      pattern transfer into a hardmask layer via commonly used etch techniques and
      graphoepitaxy-based directed self-assembly using existing lithographic
      integration schemes. We believe that this novel formulation-based approach can
      easily be extended to other applications beyond nanopatterning.

PMID- 27700029
TI  - Assessing the Increase in Specific Surface Area for Electrospun Fibrous Network
      due to Pore Induction.
AB  - The effect of pore induction on increasing electrospun fibrous network specific
      surface area was investigated in this study. Theoretical models based on the
      available surface area of the fibrous network and exclusion of the surface area
      lost due to fiber-to-fiber contacts were developed. The models for calculation of
      the excluded area are based on Hertzian, Derjaguin-Muller-Toporov (DMT), and
      Johnson-Kendall-Roberts (JKR) contact models. Overall, the theoretical models
      correlated the network specific surface area to the material properties including
      density, surface tension, Young's modulus, Poisson's ratio, as well as network
      physical properties, such as density and geometrical characteristics including
      fiber radius, fiber aspect ratio and network thickness. Pore induction proved to
      increase the network specific surface area up to 52%, compared to the maximum
      surface area that could be achieved by nonporous fiber network with the same
      physical properties and geometrical characteristics. The model based on Johnson
      Kendall-Roberts contact model describes accurately the fiber-to-fiber contact
      area under the experimental conditions used for pore generation. The experimental
      results and the theoretical model based on Johnson-Kendall-Roberts contact model
      show that the increase in network surface area due to pore induction can reach to
      up to 58%.

PMID- 27700030
TI  - Air Cushion Convection Inhibiting Icing of Self-Cleaning Surfaces.
AB  - Anti-icing surfaces/interfaces are of considerable importance in various
      engineering fields under natural freezing environment. Although superhydrophobic
      self-cleaning surfaces show good anti-icing potentials, promotion of these
      surfaces in engineering applications seems to enter a "bottleneck" stage. One of
      the key issues is the intrinsic relationship between superhydrophobicity and
      icephobicity is unclear, and the dynamic action mechanism of "air cushion" (a key
      internal factor for superhydrophobicity) on icing suppression was largely
      ignored. Here we report that icing inhibition (i.e., icing-delay) of self
      cleaning surfaces is mainly ascribed to air cushion and its convection. We
      experimentally found air cushion on the porous self-cleaning coating under vacuum
      environments and on the water/ice-coating interface at low temperatures. The
      icing-delay performances of porous self-cleaning surfaces compared with bare
      substrate, up to 10-40 min under 0 to ~-4  degrees C environments close to
      freezing rain, have been accurately real-time recorded by a novel synergy method
      including high-speed photography and strain sensing voltage. Based on the
      experimental results, we innovatively propose a physical model of "air cushion
      convection inhibiting icing", which envisages both the static action of trapped
      air pocket without air flow and dynamic action of air cushion convection. Gibbs
      free energy of water droplets increased with the entropy of air derived from heat
      and mass transfer between warmer air underneath water droplets and colder
      surrounding air, resulting in remarkable ice nucleation delay. Only when air
      cushion convection disappears can ice nucleation be triggered on suitable Gibbs
      free energy conditions. The fundamental understanding of air cushion on anti
      icing is an important step toward designing optimal anti-icing surfaces for
      practical engineering application.

PMID- 27700031
TI  - Engineering Gold Nanoparticles in Compass Shape with Broadly Tunable Plasmon
      Resonances and High-Performance SERS.
AB  - We present the uniform and high-yield synthesis of a novel gold nanostructure of
      compass shape composed of a Au sphere at the central and two gradually thinning
      conical tips at the opposed poles. The Au compass shapes were synthesized through
      a seed-mediated growth approach employing a binary mixture of
      cetyltrimethylammonium bromide (CTAB) and sodium oleate (NaOL) as the structure
      directing agents. Under the condition of single surfactant (CTAB), the spherical
      seeds tend to grow into larger spherical Au nanoparticles (NPs); while the
      spherical seeds favor the formation of Au compass shaped NPs using two mixed
      surfactants (CTAB/NaOL). The reaction kinetics clearly shows a growth mechanism
      of Au compass shaped NPs. Interestingly, due to their anisotropic structure, Au
      compass shaped NPs show two distinctive plasmonic resonances, similar to those
      from Au nanorods. Particularly, the longitudinal surface plasmon resonances of Au
      compass shaped NPs exhibit a broadly tunable range from 600 to 865 nm. In
      addition, the obtained Au compass shaped NPs can be self-assembled into a two
      dimensional monolayer with closely packed and highly aligned NPs, which results
      in periodic arrays of overlapped Au tips, generating hot spots for high
      performance surface-enhanced Raman scattering.

PMID- 27700032
TI  - Sodium Ion Diffusion in Nasicon (Na3Zr2Si2PO12) Solid Electrolytes: Effects of
      Excess Sodium.
AB  - The Na superionic conductor (aka Nasicon, Na1+xZr2SixP3-xO12, where 0 <= x <= 3)
      is one of the promising solid electrolyte materials used in advanced molten Na
      based secondary batteries that typically operate at high temperature (over ~270 
      degrees C). Nasicon provides a 3D diffusion network allowing the transport of the
      active Na-ion species (i.e., ionic conductor) while blocking the conduction of
      electrons (i.e., electronic insulator) between the anode and cathode compartments
      of cells. In this work, the standard Nasicon (Na3Zr2Si2PO12, bare sample) and 10
      at% Na-excess Nasicon (Na3.3Zr2Si2PO12, Na-excess sample) solid electrolytes were
      synthesized using a solid-state sintering technique to elucidate the Na diffusion
      mechanism (i.e., grain diffusion or grain boundary diffusion) and the impacts of
      adding excess Na at relatively low and high temperatures. The structural,
      thermal, and ionic transport characterizations were conducted using various
      experimental tools including X-ray diffraction (XRD), differential scanning
      calorimetry (DSC), scanning electron microscopy (SEM), and electrochemical
      impedance spectroscopy (EIS). In addition, an ab initio atomistic modeling study
      was carried out to computationally examine the detailed microstructures of
      Nasicon materials, as well as to support the experimental observations. Through
      this combination work comprising experimental and computational investigations,
      we show that the predominant mechanisms of Na-ion transport in the Nasicon
      structure are the grain boundary and the grain diffusion at low and high
      temperatures, respectively. Also, it was found that adding 10 at% excess Na could
      give rise to a substantial increase in the total conductivity (e.g., ~1.2 * 10-1
      S/cm at 300  degrees C) of Nasicon electrolytes resulting from the enlargement of
      the bottleneck areas in the Na diffusion channels of polycrystalline grains.

PMID- 27700033
TI  - Biosensing Probe for Quality Control Monitoring of the Structural Integrity of
      Therapeutic Antibodies.
AB  - Ideal quality control of therapeutic antibodies involves analytical techniques
      with high-sensitivity, high-resolution, and high-throughput performance. Few
      technologies that assess the physicochemical heterogeneity of antibodies,
      however, meet all the required demands. We developed a biosensing method for the
      quality control of therapeutic antibodies based on an artificial protein, AF.2A1,
      which discriminates between the native and the non-native three-dimensional
      structures of immunoglobulin G (IgG). AF.2A1 specifically recognized non-native
      IgG spiked into a solution of native IgG, thereby making it possible to detect
      contamination by a small amount of non-native IgG, which is difficult using
      conventional size-based separation or spectroscopic techniques. Using AF.2A1 as
      an analytical probe, we determined the concentration of non-native IgG formed
      under various pH conditions. The probe was also applicable to accelerated tests
      of the long-term stability of a therapeutic antibody, allowing monitoring of the
      formation of non-native IgG at elevated temperatures and extended periods of
      storage. AF.2A1, a proteinous probe, can be combined with established methods or
      devices to achieve high-throughput assays and provides the potential for probe
      based biosensing for the quality control of therapeutic antibodies.

PMID- 27700034
TI  - Model-guided interface probe arrangement for sensitive protein detection.
AB  - A wide range of analytical techniques in bioanalysis rely on surface-based
      biomolecular detection, which requires the confinement of probes onto
      heterogeneous surface to react with targets. Probe arrangement on the interface
      is critical for target recognition and determines assay performance. Much effort
      has been devoted to screen the optimized probe arrangement according to
      experimental tests. Such a data-driven posteriori pattern faces low efficiency,
      ambiguous orientation and possible deviated tested ranges from the best case.
      Herein we demonstrate that a model can effectively guide probe arrangement onto
      interface to facilitate probe-target recognition, embodied by assay of human
      telomerase activity with DNA-conjugated gold nanoparticles (AuNPs). Both
      theoretical calculation and experimental results indicate that telomerase
      activity is maximized on AuNP surface under guidance of model. The detection
      limit is at least one order of magnitude lower than that of AuNP bearing densely
      packed DNA, comparable to that of TRAP. Model-guided interface probe arrangement
      is proved to be highly useful in regulating interface recognition and may offer a
      new paradigm to promote surface-based biomolecular detection.

PMID- 27700035
TI  - NaSn2As2: An Exfoliatable Layered van der Waals Zintl Phase.
AB  - The discovery of new families of exfoliatable 2D crystals that have diverse sets
      of electronic, optical, and spin-orbit coupling properties, enables the
      realization of unique physical phenomena in these few-atom thick building blocks
      and in proximity to other materials. Herein, using NaSn2As2 as a model system, we
      demonstrate that layered Zintl phases having the stoichiometry ATt2Pn2 (A = Group
      1 or 2 element, Tt = Group 14 tetrel element and Pn = Group 15 pnictogen element)
      and feature networks separated by van der Waals gaps can be readily exfoliated
      with both mechanical and liquid-phase methods. We identified the symmetries of
      the Raman active modes of the bulk crystals via polarized Raman spectroscopy.
      Both bulk and few-layered NaSn2As2 samples are resistant towards oxidation, with
      only the top surface oxidizing in ambient conditions over a couple of days.
      Employing angle-resolved photoemission spectroscopy (ARPES), density functional
      theory (DFT), and transport on bulk and exfoliated samples, we show that NaSn2As2
      is a highly conducting 2D semimetal, with resistivities on the order of 10-6
      Omega.m. Due to peculiarities in the band structure, the dominating p-type
      carriers at low temperature are nearly compensated by the opening of n-type
      conduction channels as temperature increases. This work further expands the
      family of exfoliatable 2D materials to layered van der Waals Zintl phases,
      opening up opportunities in electronics and spintronics.

PMID- 27700036
TI  - Tailoring Material Stiffness by Filler Particle Organization.
AB  - In the context of emerging methods to control particle organization in particle
      matrix composite materials, we explore, using finite element analysis, how to
      modulate the material bulk mechanical stiffness. Compared to a composite
      containing randomly distributed particles, material stiffness is enhanced 100
      fold when filler particles are aligned into linear chains lying parallel to the
      loading direction. In contrast, chains aligned perpendicular to that direction
      produce negligible stiffness change. These outcomes reveal how zigzag chains,
      which provide intermediate results, can modulate stiffness. The stiffness
      decreases gradually with increasing zigzag angle theta over a range spanning two
      orders of magnitude.

PMID- 27700037
TI  - ICPMS-based Specific Quantification of Phosphotyrosine: A Gallium-tagging and
      Tyrosine-phosphatase Mediated Strategy.
AB  - Low-abundance tyrosine phosphorylation is crucial to not only normal but also
      aberrant life processes. We designed and synthesized a photocleavable magnetic
      nanoparticle-based gallium tag for tagging and enrichment as well as UV-release
      of the phosphate-bearing molecules/ions in cells. HPLC/71Ga species-unspecific
      isotope dilution (71Ga-SUID) ICP-MS was subsequently developed for specific and
      absolute quantification of phosphotyrosine (pY) under the assistance of a protein
      tyrosine phosphatase-1B (PTP-1B). pY quantification was thus achieved via
      determination of Ga in the Ga-phosphate complexes that come exclusively from the
      Ga-tagged pY. In this way, the method detection limit of pY reached down to 30
      amol with the RSD lower than 5.70 % (n = 5 at pmol level). Feasibility of this
      proposed method was validated using VNQIGTLSEpYIK, VNQIGTLpSEpYIK and
      extracellular regulated protein kinase 1 peptide (-pTEpY-) standards with the
      recovery more than 96 % (n = 5). It was applied to the absolute quantification of
      pY in human breast cancer MCF-7 cells, indicating that pY increased by 1.60 nmol
      (61.1 %) in 3.0 * 106 MCF-7 cells after 100 nM insulin stimulation. We believe
      that, not limited to pY quantification, this element-tagging and protease
      specific reaction mediated ICP-MS methodology will pave a simple path for ever
      more applications of ICP-MS to the studies of quantitative protein post
      translational modifications (PTMs) when suitable element-tags are designed and
      specific proteases are available towards targeted PTMs.

PMID- 27700038
TI  - Energy and Electron Transfer Cascade in Self-Assembled Bilayer Dye-Sensitized
      Solar Cells.
AB  - Current high efficiency dye-sensitized solar cells (DSSCs) rely on the
      incorporation of multiple chromophores, via either codeposition or preformed
      assemblies, as a means of increasing broad band light absorption. These
      strategies have some inherent limitations including decreased total light
      absorption by each of the dyes, low surface loadings, and complex synthetic
      procedures. In this report, we introduce an alternative strategy, self-assembled
      bilayers, as a simple, stepwise method of incorporating two complementary
      chromophores into a DSSC. The bilayer devices exhibit a 10% increase in Jsc, Voc,
      and eta over the monolayer devices due to increased incident photon-to-electron
      conversion efficiency across the entire visible spectrum and slowed recombination
      losses at the interface. Directional energy and electron transfer toward the
      metal oxide surface are key steps in the bilayer photon-to-current generation
      process. These results are important as they open the door to a new architecture
      for harnessing broadband light in dye-sensitized devices.

PMID- 27700039
TI  - Digital Microfluidics for Immunoprecipitation.
AB  - Immunoprecipitation (IP) is a common method for isolating a targeted protein from
      a complex sample such as blood, serum, or cell lysate. In particular, IP is often
      used as the primary means of target purification for the analysis by mass
      spectrometry of novel biologically derived pharmaceuticals, with particular
      utility for the identification of molecules bound to a protein target.
      Unfortunately, IP is a labor-intensive technique, is difficult to perform in
      parallel, and has limited options for automation. Furthermore, the technique is
      typically limited to large sample volumes, making the application of IP cleanup
      to precious samples nearly impossible. In recognition of these challenges, we
      introduce a method for performing microscale IP using magnetic particles and
      digital microfluidics (DMF-IP). The new method allows for 80% recovery of model
      proteins from approximately microliter volumes of serum in a sample-to-answer run
      time of approximately 25 min. Uniquely, analytes are eluted from these small
      samples in a format compatible with direct analysis by mass spectrometry. To
      extend the technique to be useful for large samples, we also developed a macro-to
      microscale interface called preconcentration using liquid intake by paper (P
      CLIP). This technique allows for efficient analysis of samples >100* larger than
      are typically processed on microfluidic devices. As described herein, DMF-IP and
      P-CLIP-DMF-IP are rapid, automated, and multiplexed methods that have the
      potential to reduce the time and effort required for IP sample preparations with
      applications in the fields of pharmacy, biomarker discovery, and protein biology.

PMID- 27700040
TI  - Preparation of Hybrid Gold/Polymer Nanocomposites and Their Application in a
      Controlled Antibacterial Assay.
AB  - In this work, we report a photosensitizer-loaded hybrid nanostructure that shows
      high antibacterial efficiency after surface interaction with a lectin protein.
      Gold nanoparticles were generated on the polymer nanoparticle surface through an
      in situ reduction method and behaved as a plasmonic amplifier. After conjugation
      of the photosensitizer rose bengal onto the hybrid nanoparticles, higher
      phosphorescence intensity and generation of reactive oxygen species (ROS) were
      observed. The nanocomposites showed high antibacterial efficiency toward Gram
      negative Escherichia coli treated with a lectin protein concanavalin A, which
      caused self-assembly of the bacteria and nanoparticles. Therefore, the as
      prepared nanostructure considerably improved the effectiveness of ROS toward
      bacteria and provides an alternative strategy for controlled antibacterial
      assays.

PMID- 27700041
TI  - Determination of Fragrance Allergens by Ultraviolet Femtosecond Laser Ionization
      Mass Spectrometry.
AB  - The allergenic compounds listed in the Cosmetics Directive by the Scientific
      Committee for Consumer Safety were analyzed by gas chromatography combined with
      multiphoton ionization mass spectrometry using a femtosecond laser emitting at
      200 and 267 nm as the ionization source. The limits of detection were less than
      100 pg/MUL for all of the compounds, permitting them to be measured in actual
      samples that were simply prepared by a 100-fold dilution of the original sample.
      The ionization process was investigated for the 26 allergens, some of which had
      no absorption band, even in the far-UV region. As a result, nonresonant two
      photon ionization was found to be the most sensitive and universal method for the
      trace analysis of these compounds, because of the short pulse width, i.e., a high
      peak power, of the femtosecond laser used. It should be noted that the excess
      energy can be reduced by using a laser emitting at longer wavelengths (267 nm)
      and that fragmentation can be suppressed, especially for a molecule that contains
      a long side chain. Three commercially available perfumes were measured, and more
      than 10 allergenic compounds were determined.

PMID- 27700043
TI  - Triboelectricity Generation from Vertically Aligned Carbon Nanotube Arrays.
AB  - We explore the use of vertically aligned carbon nanotube (VACNT) arrays as an
      electrode in a triboelectric nanogenerator (TENG) that harvests mechanical energy
      and converts it to electrical energy. When VACNT arrays, 1 cm2 in area, are
      mechanically contacted with PET and PTFE counter electrodes in vertical contact
      separation mode, currents up to 0.16 uA and 0.21 uA, and voltages up to 1.42 V
      and 3.20 V are obtained, respectively. The VACNT TENG output remains stable even
      after over 20,000 continuous contact cycles. A 0.47 uF capacitor is successfully
      charged to 4.5 V in 60 s using a VACNT-PTFE triboelectric nanogenerator (TENG)
      prototype.

PMID- 27700042
TI  - Protein-Metal Organic Framework Hybrid Composites with Intrinsic Peroxidase-like
      Activity as a Colorimetric Biosensing Platform.
AB  - Artificial enzyme mimetics have received considerable attention because natural
      enzymes have some significant drawbacks, including enzyme autolysis, low
      catalytic activity, poor recovery, and low stability to environmental changes.
      Herein, we demonstrated a facile approach for one-pot synthesis of hemeprotein
      metal organic framework hybrid composites (H-MOFs) by using bovine hemoglobin
      (BHb) and zeolitic imidazolate framework-8 (ZIF-8) as a model reaction system.
      Surprisingly, the new hybrid composites exhibit 423% increase in peroxidase-like
      catalytic activity compared to free BHb. Taking advantages of the unique pore
      structure of H-MOFs with high catalytic property, a H-MOFs-based colorimetric
      biosensing platform was newly constructed and applied for the fast and sensitive
      detection of hydrogen peroxide (H2O2) and phenol. The corresponding detection
      limits as low as 1.0 MUM for each analyte with wide linear ranges (0-800 MUM for
      H2O2 and 0-200 MUM for phenol) were obtained by naked-eye visualization.
      Significantly, a sensitive and selective method for visual assay of trace H2O2 in
      cells and phenol in sewage was achieved with this platform. The stability of H
      MOFs was also examined, and excellent reproducibility and recyclability without
      losing in their activity were observed. In addition, the general applicability of
      H-MOFs was also investigated by using other hemeproteins (horseradish peroxidase,
      and myoglobin), and the corresponding catalytic activities were 291% and 273%
      enhancement, respectively. This present work not only expands the application of
      MOFs but also provides an alternative technique for biological and environmental
      sample assay.

PMID- 27700044
TI  - Yolk-Shell Ni@SnO2 Composites with a Designable Interspace To Improve the
      Electromagnetic Wave Absorption Properties.
AB  - In this study, yolk-shell Ni@SnO2 composites with a designable interspace were
      successfully prepared by the simple acid etching hydrothermal method. The
      Ni@void@SnO2 composites were characterized by X-ray diffraction, Fourier
      transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning
      electron microscopy, and transmission electron microscopy. The results indicate
      that interspaces exist between the Ni cores and SnO2 shells. Moreover, the void
      can be adjusted by controlling the hydrothermal reaction time. The unique yolk
      shell Ni@void@SnO2 composites show outstanding electromagnetic wave absorption
      properties. A minimum reflection loss (RLmin) of -50.2 dB was obtained at 17.4
      GHz with absorber thickness of 1.5 mm. In addition, considering the absorber
      thickness, minimal reflection loss, and effective bandwidth, a novel method to
      judge the effective microwave absorption properties is proposed. On the basis of
      this method, the best microwave absorption properties were obtained with a 1.7 mm
      thick absorber layer (RLmin= -29.7 dB, bandwidth of 4.8 GHz). The outstanding
      electromagnetic wave absorption properties stem from the unique yolk-shell
      structure. These yolk-shell structures can tune the dielectric properties of the
      Ni@air@SnO2 composite to achieve good impedance matching. Moreover, the
      designable interspace can induce interfacial polarization, multiple reflections,
      and microwave plasma.

PMID- 27700045
TI  - Specific Detection of Cellular Glutamine Hydrolysis in Live Cells Using HNCO
      Triple Resonance NMR.
AB  - Glutamine plays key roles as a biosynthetic precursor or an energy source in
      cancers, and interest in its metabolism is rapidly growing. However, the proper
      evaluation of glutamine hydrolysis, the very first reaction in the entire
      glutaminolysis, has been difficult. Here, we report a triple resonance NMR-based
      assay for specific detection of glutaminase activity carrying out this reaction
      using stable-isotope labeled glutamine. Compared to conventional methods
      involving coupled enzyme assays, the proposed approach is direct because it
      detects the presence of the H-N-CO amide spin system. In addition, the method is
      unique in enabling the measurement of glutamine hydrolysis reaction in real-time
      in live cells. The approach was applied to investigating the effects of a
      glutaminase inhibitor and the inhibitory effects of glucose on glutamine
      metabolism in live cells. It can be easily applied to studying other signals that
      affect cellular glutamine metabolism.

PMID- 27700046
TI  - Laser-Assisted Focused He+ Ion Beam Induced Etching with and without XeF2 Gas
      Assist.
AB  - Focused helium ion (He+) milling has been demonstrated as a high-resolution
      nanopatterning technique; however, it can be limited by its low sputter yield as
      well as the introduction of undesired subsurface damage. Here, we introduce
      pulsed laser- and gas-assisted processes to enhance the material removal rate and
      patterning fidelity. A pulsed laser-assisted He+ milling process is shown to
      enable high-resolution milling of titanium while reducing subsurface damage in
      situ. Gas-assisted focused ion beam induced etching (FIBIE) of Ti is also
      demonstrated in which the XeF2 precursor provides a chemical assist for enhanced
      material removal rate. Finally, a pulsed laser-assisted and gas-assisted FIBIE
      process is shown to increase the etch yield by ~9* relative to the pure He+
      sputtering process. These He+ induced nanopatterning techniques improve material
      removal rate, in comparison to standard He+ sputtering, while simultaneously
      decreasing subsurface damage, thus extending the applicability of the He+ probe
      as a nanopattering tool.

PMID- 27700047
TI  - Polymer Colloidal Sphere-Based Hybrid Solid Immersion Lens for Optical Super
      Resolution Imaging.
AB  - Optical microscope is widely used real-time investigation tool, but usually
      suffers from low resolution due to Abbe diffraction limit. Herein, we design and
      successfully synthesize ZrO2/polymer hybrid colloidal microspheres with as high
      as 47.5 wt% inorganic nanoparticles by suspension polymerization of 9,9'-bis[4-(2
      acryloyloxyethyloxy) phenyl] fluorene (BAEPF). Owing to the homogeneous
      dispersion, high density and high refractive index of inorganic nanoparticles and
      deformability of polymer, the obtained ZrO2/poly(BAEPF) hybrid colloidal
      microspheres have high refractive index, optical transparency and controllable
      curvature, and thus can be directly used as a hybrid solid immersion lens (hSIL)
      for optical microscope, achieving super-resolution imaging of 50 nm even 45 nm
      under a standard white light or blue light optical microscopes, which is far
      beyond the diffraction limit for visible light optical microscopes. Our hSIL
      design concept and strategy demonstrate efficient, fast and solid practical
      potentials for optical super-resolution imaging, and may also create another
      application possibility for polymer colloidal spheres.

PMID- 27700048
TI  - Growth of One-Dimensional RuO2 Nanowires on g-Carbon Nitride: An Active and
      Stable Bifunctional Electrocatalyst for Hydrogen and Oxygen Evolution Reactions
      at All pH Values.
AB  - Development of highly efficient and durable bifunctional electrocatalyst for
      hydrogen and oxygen evolution reactions (HER and OER) is essential for efficient
      solar fuel generation. The commercial RuO2 or RuO2-based catalysts are highly
      active toward OER, but their poor stability under different operating conditions
      is the main obstacle for their commercialization. Herein, we report growth of one
      dimensional highly crystalline RuO2 nanowires on carbon nitride (1D-RuO2-CNx) for
      their applications in HER and OER at all pH values. The 1D-RuO2-CNx, as an OER
      catalyst, exhibits a low onset overpotential of ~200 mV in both acidic and basic
      media, whereas Tafel slopes are 52 and 56 mV/dec in acidic and basic media,
      respectively. This catalyst requires a low overpotential of 250 and 260 mV to
      drive the current density of 10 mA cm-2 in acidic and basic media, respectively.
      The mass activity of 1D-RuO2-CNx catalyst is 352 mA mg-1, which is ~14 times
      higher than that of commercial RuO2. Most importantly, the 1D-RuO2-CNx catalyst
      has remarkably higher stability compared to commercial RuO2. This catalyst also
      exhibits superior HER activity with a current density of 10 mAcm-2 at ~93 and 95
      mV in acidic and basic media. The HER Tafel slopes of this catalyst are 40 mV/dec
      in acidic condition and 70 mV/dec in basic condition. The HER activity of this
      catalyst is slightly lower than Pt/C in acidic media, whereas in basic media it
      is comparable or even better than that of Pt/C at higher overpotentials. The HER
      stability of this catalyst is also better than that of Pt/C in all pH solutions.
      This superior catalytic activity of 1D-RuO2-CNx composite can be attributed to
      catalyst-support interaction, enhanced mass and electron transport, one
      dimensional morphology, and highly crystalline rutile RuO2 structure.

PMID- 27700050
TI  - Approaches to Study Phosphatases.
AB  - Phosphatases play key roles in normal physiology and diseases. Studying
      phosphatases has been both essential and challenging, and the application of
      conventional genetic and biochemical methods has led to crucial but still limited
      understanding of their mechanisms, substrates, and exclusive functions within
      highly intricate networks. With the advances in technologies such as cellular
      imaging and molecular and chemical biology in terms of sensitive tools and
      methods, the phosphatase field has thrived in the past years and has set new
      insights for cell signaling studies and for therapeutic development. In this
      review, we give an overview of the existing interdisciplinary tools for
      phosphatases, give examples on how they have been applied to increase our
      understanding of these enzymes, and suggest how they-and other tools yet barely
      used in the phosphatase field-might be adapted to address future questions and
      challenges.

PMID- 27700051
TI  - Large planar pi-conjugated porphyrin for interfacial engineering in p-i-n
      perovskite solar cells.
AB  - In hybrid organic-inorganic perovskite solar cells (PSCs), interfacial
      engineering can efficiently improve the photovoltaic performance. In this work,
      the planar pi-conjugated porphyrin, zinc(II) 5,10,15,20-tetrakis[5-(p
      acetylthiopentyloxy)phenyl]porphyrin, was developed to modify the interface
      between poly(3,4-ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS)
      and perovskite. The modified devices increased their highest power conversion
      efficiency (PCE) to 14.05% relative to 11.35% for the reference devices without
      modification. Such enhancement in efficiency is mainly attributed to the improved
      open-circuit voltage (Voc) and fill factor (FF), which benefit from fast hole
      extraction and low charge recombination after the employment of well-aligned
      interlayer.

PMID- 27700049
TI  - Pharmacodynamic Relationships between Duration of Action of JDTic-like Kappa
      Opioid Receptor Antagonists and Their Brain and Plasma Pharmacokinetics in Rats.
AB  - JDTic is a potent and selective kappa-opioid receptor (KOR) antagonist that
      reverses U50,488-induced diuresis in rats. It partitions into brain with a
      duration of action lasting for weeks. In a search for KOR antagonists that do not
      accumulate in the brain, we compared single doses of five methylated JDTic
      analogs (RTI-97, -194, -212, -240, and -241) for reversal of U50,488 diuresis and
      pharmacokinetic (PK) properties. All six compounds showed potent and selective
      KOR antagonism in a [35S]GTPgammaS binding assay. Plasma half-lives ranged from
      24 to 41 h and brain half-lives from 24 to 76 h. JDTic and RTI-194 showed
      increasing brain to plasma ratios over time, indicating increasing partitioning
      into brain and a longer duration of action for reversal of diuresis than did RTI
      97. RTI-240 did not show significant brain accumulation. RTI-212 showed no
      substantive difference between brain and plasma levels and was inactive against
      diuresis. RTI-241, with a lower brain to plasma ratio than JDTic and RTI-194,
      formed JDTic as a metabolite, which still reduced diuresis after 9 weeks. The
      fact that the duration of action was correlated with the brain to blood plasma
      ratios and area under the concentration-time curves suggests that PK properties
      could help to predict safety and acceptable duration of action for KOR
      antagonists.

PMID- 27700052
TI  - Cubic Re6+ (5d1) Double Perovskites, Ba2MgReO6, Ba2ZnReO6, and Ba2Y2/3ReO6:
      Magnetism, Heat Capacity, MUSR, and Neutron Scattering Studies and Comparison
      with Theory.
AB  - Double perovskites (DP) of the general formula Ba2MReO6, where M = Mg, Zn, and
      Y2/3, all based on Re6+ (5d1, t2g1), were synthesized and studied using
      magnetization, heat capacity, muon spin relaxation, and neutron-scattering
      techniques. All are cubic, Fm3m, at ambient temperature to within the resolution
      of the X-ray and neutron diffraction data, although the muon data suggest the
      possibility of a local distortion for M = Mg. The M = Mg DP is a ferromagnet, Tc
      = 18 K, with a saturation moment ~0.3 bohr magnetons at 3 K. There are two
      anomalies in the heat capacity: a sharp feature at 18 K and a broad maximum
      centered near 33 K. The total entropy loss below 45 K is 9.68 e.u., which
      approaches R ln 4 (11.52 e.u.) supporting a j = 3/2 ground state. The unit cell
      constants of Ba2MgReO6 and the isostructural, isoelectronic analogue, Ba2LiOsO6,
      differ by only 0.1%, yet the latter is an anti-ferromagnet. The M = Zn DP also
      appears to be a ferromagnet, Tc = 11 K, MUsat(Re) = 0.1 MUB. In this case the
      heat capacity shows a somewhat broad peak near 10 K and a broader maximum at ~33
      K, behavior that can be traced to a smaller particle size, ~30 nm, for this
      sample. For both M = Mg and Zn, the low-temperature magnetic heat capacity
      follows a T3/2 behavior, consistent with a ferromagnetic spin wave. An attempt to
      attribute the broad 33 K heat capacity anomalies to a splitting of the j = 3/2
      state by a crystal distortion is not supported by inelastic neutron scattering,
      which shows no transition at the expected energy of ~7 meV nor any transition up
      to 100 meV. However, the results for the two ferromagnets are compared to the
      theory of Chen, Pereira, and Balents, and the computed heat capacity predicts the
      two maxima observed experimentally. The M = Y2/3 DP, with a significantly larger
      cell constant (3%) than the ferromagnets, shows predominantly anti-ferromagnetic
      correlations, and the ground state is complex with a spin frozen component Tg =
      16 K from both direct current and alternating current susceptibility and MUSR
      data but with a persistent dynamic component. The low-temperature heat capacity
      shows a T1 power law. The unit cell constant of B = Y2/3 is less than 1% larger
      than that of the ferromagnetic Os7+ (5d1) DP, Ba2NaOsO6.

PMID- 27700053
TI  - Sortase A-Mediated Metabolic Enzyme Ligation in Escherichia coli.
AB  - We demonstrate metabolic enzyme ligation using a transpeptidase (Staphylococcal
      sortase A) in the microbial cytoplasm for the redirection of metabolic flux
      through metabolic channeling. Here, sortase A expression was controlled by the
      lac promoter to trigger metabolic channeling by the addition of isopropyl-beta-d
      thiogalactopyranoside (IPTG). We tested covalent linking of pyruvate-formate
      lyase and phosphate acetyltransferase by sortase A-mediated ligation and
      evaluated the production of acetate. The time point of addition of IPTG was not
      critical for facilitating metabolic enzyme ligation, and acetate production
      increased upon expression of sortase A. These results show that sortase A
      mediated enzyme ligation enhances an acetate-producing flux in E. coli. We have
      validated that sortase A-mediated enzyme ligation offers a metabolic channeling
      approach to redirect a central flux to a desired flux.

PMID- 27700054
TI  - Electron Transfer and Solvent-Mediated Electronic Localization in Molecular
      Photocatalysis.
AB  - This work provides a detailed mechanism for electron transfer in a
      heterodinuclear complex designed as a model system in which to study homogeneous
      molecular photocatalysis. With efficient Born-Oppenheimer molecular dynamics
      simulations, we show how intermediate, charge-separated states can mediate the
      electron transfer. We observe how Jahn-Teller distortion effects play out in
      solution, when the molecule has energetically close-lying states, and how this
      distortion is averaged out in the thermal sampling. Finally, we demonstrate how
      the solvent helps stabilize and localize the separated charge. The information on
      the electronic configuration and separate states is of key importance for
      designing next-generation photocatalysts.

PMID- 27700055
TI  - Controlling Citrate Synthase Expression by CRISPR/Cas9 Genome Editing for n
      Butanol Production in Escherichia coli.
AB  - Genome editing using CRISPR/Cas9 was successfully demonstrated in Esherichia coli
      to effectively produce n-butanol in a defined medium under microaerobic
      condition. The butanol synthetic pathway genes including those encoding oxygen
      tolerant alcohol dehydrogenase were overexpressed in metabolically engineered E.
      coli, resulting in 0.82 g/L butanol production. To increase butanol production,
      carbon flux from acetyl-CoA to citric acid cycle should be redirected to
      acetoacetyl-CoA. For this purpose, the 5'-untranslated region sequence of gltA
      encoding citrate synthase was designed using an expression prediction program,
      UTR designer, and modified using the CRISPR/Cas9 genome editing method to reduce
      its expression level. E. coli strains with decreased citrate synthase expression
      produced more butanol and the citrate synthase activity was correlated with
      butanol production. These results demonstrate that redistributing carbon flux
      using genome editing is an efficient engineering tool for metabolite
      overproduction.

PMID- 27700057
TI  - Phenanthrene Bioavailability and Toxicity to Daphnia magna in the Presence of
      Carbon Nanotubes with Different Physicochemical Properties.
AB  - Studies investigating the effect of carbon nanotubes (CNTs) on the
      bioavailability and toxicity of hydrophobic organic compounds in aquatic
      environments have generated contradictory results, and the influence of different
      CNT properties remains unknown. Here, the adsorption of the polycyclic aromatic
      hydrocarbon phenanthrene (70-735 MUg/L) to five types of CNTs exhibiting
      different physical and chemical properties was studied. The CNTs were dispersed
      in the presence of natural organic matter (nominally 20 mg/L) in order to
      increase the environmental relevance of the study. Furthermore, the
      bioavailability and toxicity of phenanthrene to Daphnia magna in the absence and
      presence of dispersed CNTs was investigated. Both CNT dispersion and adsorption
      of phenanthrene appeared to be influenced by CNT physical properties (diameter
      and specific surface area). However, dispersion and phenanthrene adsorption was
      not influenced by CNT surface chemical properties (surface oxygen content), under
      the conditions tested. Based on nominal phenanthrene concentrations, a reduction
      in toxicity to D. magna was observed during coexposure to phenanthrene and two
      types of CNTs, while for the others, no influence on phenanthrene toxicity was
      observed. Based on freely dissolved concentrations, however, an increased
      toxicity was observed in the presence of all CNTs, indicating bioavailability of
      CNT-adsorbed phenanthrene to D. magna.

PMID- 27700056
TI  - Hygroscopic Properties and Respiratory System Deposition Behavior of Particulate
      Matter Emitted By Mining and Smelting Operations.
AB  - This study examines size-resolved physicochemical data for particles sampled near
      mining and smelting operations and a background urban site in Arizona with a
      focus on how hygroscopic growth impacts particle deposition behavior. Particles
      with aerodynamic diameters between 0.056-18 MUm were collected at three sites:
      (i) an active smelter operation in Hayden, AZ, (ii) a legacy mining site with
      extensive mine tailings in Iron King, AZ, and (iii) an urban site, inner-city
      Tucson, AZ. Mass size distributions of As and Pb exhibit bimodal profiles with a
      dominant peak between 0.32 and 0.56 MUm and a smaller mode in the coarse range
      (>3 MUm). The hygroscopicity profile did not exhibit the same peaks owing to
      dependence on other chemical constituents. Submicrometer particles were generally
      more hygroscopic than supermicrometer ones at all three sites with finite water
      uptake ability at all sites and particle sizes examined. Model calculations at a
      relative humidity of 99.5% reveal significant respiratory system particle
      deposition enhancements at sizes with the largest concentrations of toxic
      contaminants. Between dry diameters of 0.32 and 0.56 MUm, for instance, ICRP and
      MPPD models predict deposition fraction enhancements of 171%-261% and 33%-63%,
      respectively, at the three sites.

PMID- 27700058
TI  - The Rate of Crude Oil Biodegradation in the Sea.
AB  - Various groups have studied the rate of oil biodegradation in the sea over many
      years, but with no consensus on results. This can be attributed to many factors,
      but we show here that the principal confounding influence is the concentration of
      oil used in different experiments. Because of dilution, measured concentrations
      of dispersed oil in the sea are sub-parts-per-million within a day of dispersal,
      and at such concentrations the rate of biodegradation of detectable oil
      hydrocarbons has an apparent half-life of 7-14 days. This can be contrasted with
      the rate of degradation at the higher concentrations found in oil slicks or when
      stranded on a shoreline; there the apparent half-life varies from many months to
      many years.

PMID- 27700059
TI  - Rationally Designed Redox-Sensitive Protein Hydrogels with Tunable Mechanical
      Properties.
AB  - Protein hydrogels are an important class of materials for applications in
      biotechnology and medicine. The fine-tuning of their sequence, molecular weight,
      and stereochemistry offers unique opportunities to engineer biofunctionality,
      biocompatibility, and biodegradability into these materials. Here we report a new
      family of redox-sensitive protein hydrogels with controllable mechanical
      properties composed of recombinant silk-elastin-like protein polymers (SELPs).
      The SELPs were designed and synthesized with different ratios of silk-to-elastin
      blocks that incorporated periodic cysteine residues. The cysteine-containing
      SELPs were thermally responsive in solution and rapidly formed hydrogels at body
      temperature under physiologically relevant, mild oxidative conditions. Upon
      addition of a low concentration of hydrogen peroxide at 0.05% (w/v), gelation
      occurred within minutes for the SELPs with a protein concentration of
      approximately 4% (w/v). The gelation time and mechanical properties of the
      hydrogels were dependent on the ratio of silk to elastin. These polymer designs
      also significantly affected redox-sensitive release of a highly polar model drug
      from the hydrogels in vitro. Furthermore, oxidative gelation was performed at
      other physiologically relevant temperatures, and this resulted in hydrogels with
      tunable mechanical properties, thus, providing a secondary level of control over
      hydrogel stiffness. These newly developed injectable SELP hydrogels with redox
      sensitive features and tunable mechanical properties may be potentially useful as
      biomaterials with broad applications in controlled drug delivery and tissue
      engineering.

PMID- 27700061
TI  - Ditechnetium Heptoxide Revisited: Solid-State, Gas-Phase, and Theoretical
      Studies.
AB  - Ditechnetium heptoxide was synthesized from the oxidation of TcO2 with O2 at 450 
      degrees C and characterized by single-crystal X-ray diffraction, electron-impact
      mass spectrometry (EI-MS), and theoretical methods. Refinement of the structure
      at 100 K indicates that Tc2O7 crystallizes as a molecular solid in the
      orthorhombic space group Pbca [a = 7.312(3) A, b = 5.562(2) A, c = 13.707(5) A,
      and V = 557.5(3) A3]. The Tc2O7 molecule can be described as corner-sharing TcO4
      tetrahedron [Tc---Tc = 3.698(1) A and Tc-OBri-Tc = 180.0 degrees ]. The EI-MS
      spectrum of Tc2O7 consists of both mononuclear and dinuclear species. The main
      dinuclear species in the gas-phase are Tc2O7 (100%) and Tc2O5 (56%), while the
      main mononuclear species are TcO3 (33.9%) and TcO2 (42.8%). The difference in the
      relative intensities of the M2O5 (M = Tc, Re) fragments (1.7% for Re) indicates
      that these group 7 elements exhibit different gas-phase chemistry. The solid
      state structure of Tc2O7 was investigated by density functional theory methods.
      The optimized structure of the Tc2O7 molecule is in good agreement with the
      experimental one. Simulations indicate that the more favorable geometry for the
      Tc2O7 molecule in the gas-phase is bent (Tc-OBri-Tc = 156.5 degrees ), while a
      linear geometry (Tc-OBri-Tc = 180.0 degrees ) is favored in the solid-state.

PMID- 27700060
TI  - Oxidizing Impact Induced by Mackinawite (FeS) Nanoparticles at Oxic Conditions
      due to Production of Hydroxyl Radicals.
AB  - Mackinawite (FeS) nanoparticles have been extensively tested for reducing
      contaminants under anoxic conditions, while the oxidizing impact induced by FeS
      under oxic conditions has been largely underestimated. In light of previous
      findings that hydroxyl radicals (.OH) can be produced from oxygenation of
      sediment Fe(II), herein we revealed that .OH can be produced efficiently from FeS
      oxygenation at circumneutral conditions, yielding 84.7 MUmol .OH per g FeS. Much
      more .OH was produced from the oxygenation of FeS compared with siderite, pyrite,
      and zerovalent iron nanoparticles under the same conditions. The oxidation of FeS
      was a surface-mediated process, in which O2 was transformed by the structural
      Fe(II) on FeS surface to .OH with the generation of H2O2 intermediate. A small
      proportion of Fe(II) was regenerated from the reduction of Fe(III) by FeS and S(
      II), but this proportion did not significantly contribute to .OH production. We
      further validated that the .OH produced from FeS oxygenation considerably
      contributed to the oxidation of arsenic. As the change of redox conditions from
      anoxic to oxic is common in both natural and artificial processes, our findings
      suggest that the oxidizing impact induced by FeS at oxic conditions should be
      concerned due to .OH production.

PMID- 27700063
TI  - The Unprinted Journal.

PMID- 27700062
TI  - Delaying Photobleaching of a Light-Switch Complex for Real-Time Imaging of Single
      Viral Particle Uncoating.
AB  - Photobleaching is a major obstacle in the real-time imaging of biological events,
      particularly at the single-molecule/particle level. Here, we report a strategy to
      delay photobleaching of a light-switch complex, [Ru(phen)2dppx]2+, by insertion
      of a six-cysteine peptide into virus particles. The six-cysteine peptide was
      inserted into viral protein R of HIV-1 and assembled into infectious HIV-1 viral
      particles, where it effectively delayed the photobleaching of the
      [Ru(phen)2dppx]2+ complex used to label viral genomic RNAs. This delay in
      photobleaching allowed for a monofluorescent assay to be constructed for the real
      time monitoring of viral uncoating, a poorly understood process. This novel
      strategy to delay photobleaching in infectious viral particles provides a
      powerful method to analyze viral uncoating at the single-particle level in real
      time.

PMID- 27700064
TI  - Protein kinase C Signaling in Adenoviral Infection.
AB  - Activation of protein kinase C (PKC), a serine/threonine protein kinase,
      ubiquitously influences cellular signal transduction, and has been shown to play
      a role in viral entry. In this study, we explored a role for PKC in human
      adenovirus type 37 infection of primary human corneal fibroblasts, a major target
      cell for infection. We sought evidence for an interaction between PKC activation
      and two potential downstream targets: cSrc kinase, shown previously to play a
      critical role in adenovirus signaling in these cells, and caveolin-1, reported
      earlier to be important to entry of adenovirus type 37. Infection of fibroblasts
      increased PKCalpha phosphorylation and translocation of PKCalpha from the cytosol
      to caveolin-1 containing vesicles. Virus-induced phosphorylation of both cSrc and
      AKT was abolished in cell lysates pretreated with calphostin C, a chemical
      inhibitor of PKC. Inhibition of PKC also reduced virus associated phosphorylation
      of caveolin-1, while inhibition of cSrc by the chemical inhibitor PP2 reduced
      only caveolin-1 phosphorylation, but not PKCalpha phosphorylation, in lipid
      rafts. These results suggest a role for PKCalpha upstream to both cSrc and
      caveolin-1. Phosphorylated PKCalpha was found in the same endosomal fractions as
      phosphorylated cSrc, and PKCalpha was present to a greater degree in caveolin-1
      pull downs from virus infected than mock infected cell lysates. Calphostin C also
      reduced early viral gene expression, indicating that PKCalpha activity may be
      required for viral entry. PKCalpha plays a central role in adenovirus infection
      of corneal fibroblasts and regulation of downstream molecules, including the
      important lipid raft component caveolin-1.

PMID- 27700066
TI  - Comparison of Atmospheric Pressure Chemical Ionization and Field Ionization Mass
      Spectrometry for the Analysis of Large Saturated Hydrocarbons.
AB  - Direct infusion atmospheric pressure chemical ionization mass spectrometry (APCI
      MS) was compared to field ionization mass spectrometry (FI-MS) for the
      determination of hydrocarbon class distributions in lubricant base oils. When
      positive ion mode APCI with oxygen as the ion source gas was employed to ionize
      saturated hydrocarbon model compounds (M) in hexane, only stable [M - H]+ ions
      were produced. Ion-molecule reaction studies performed in a linear quadrupole ion
      trap suggested that fragment ions of ionized hexane can ionize saturated
      hydrocarbons via hydride abstraction with minimal fragmentation. Hence, APCI-MS
      shows potential as an alternative of FI-MS in lubricant base oil analysis.
      Indeed, the APCI-MS method gave similar average molecular weights and hydrocarbon
      class distributions as FI-MS for three lubricant base oils. However, the
      reproducibility of APCI-MS method was found to be substantially better than for
      FI-MS. The paraffinic content determined using the APCI-MS and FI-MS methods for
      the base oils was similar. The average number of carbons in paraffinic chains
      followed the same increasing trend from low viscosity to high viscosity base oils
      for the two methods.

PMID- 27700067
TI  - Stability of Superhalogen Anions in the Aqueous Phase.
AB  - The issue of stability of superhalogen anions in an aqueous solution is
      investigated on the basis of theoretical calculations carried out at the
      CCSD(T)/6-311++G(d,p)//MP2/6-311++G(d,p) level for two representative negatively
      charged systems (NaF2- and AlF4-) whose fragmentation products differ in
      polarity. The presence of a water solvent is simulated independently by employing
      the polarized continuum solvation model and by involving eight H2O molecules
      explicitly to allow interactions at the molecular level. The best estimates of
      the Gibbs free energies characterizing the AlF4- and NaF2- fragmentation
      reactions in a water solvent are evaluated as equal to 33-34 and 12-14 kcal/mol,
      respectively (assuming the F- and AlF3/NaF products) or 14-15 and 26-28 kcal/mol,
      respectively (assuming the HF and AlF3OH-/NaFOH- products). The corresponding
      fragmentation routes are suggested to be nonoperative at T = 298.15 K. The
      conclusion concerning the thermodynamic stability of the AlF4- and NaF2-
      superhalogen anions in the aqueous phase is formulated and discussed.

PMID- 27700065
TI  - Imaging Taurine in the Central Nervous System Using Chemically Specific X-ray
      Fluorescence Imaging at the Sulfur K-Edge.
AB  - A method to image taurine distributions within the central nervous system and
      other organs has long been sought. Since taurine is small and mobile, it cannot
      be chemically "tagged" and imaged using conventional immuno-histochemistry
      methods. Combining numerous indirect measurements, taurine is known to play
      critical roles in brain function during health and disease and is proposed to act
      as a neuro-osmolyte, neuro-modulator, and possibly a neuro-transmitter.
      Elucidation of taurine's neurochemical roles and importance would be
      substantially enhanced by a direct method to visualize alterations, due to
      physiological and pathological events in the brain, in the local concentration of
      taurine at or near cellular spatial resolution in vivo or in situ in tissue
      sections. We thus have developed chemically specific X-ray fluorescence imaging
      (XFI) at the sulfur K-edge to image the sulfonate group in taurine in situ in ex
      vivo tissue sections. To our knowledge, this represents the first undistorted
      imaging of taurine distribution in brain at 20 MUm resolution. We report
      quantitative technique validation by imaging taurine in the cerebellum and
      hippocampus regions of the rat brain. Further, we apply the technique to image
      taurine loss from the vulnerable CA1 (cornus ammonis 1) sector of the rat
      hippocampus following global brain ischemia. The location-specific loss of
      taurine from CA1 but not CA3 neurons following ischemia reveals osmotic stress
      may be a key factor in delayed neurodegeneration after a cerebral ischemic insult
      and highlights the significant potential of chemically specific XFI to study the
      role of taurine in brain disease.

PMID- 27700068
TI  - Site Occupancies, Luminescence, and Thermometric Properties of LiY9(SiO4)6O2:Ce3+
      Phosphors.
AB  - In this work, we report the tunable emission properties of Ce3+ in an apatite
      type LiY9(SiO4)6O2 compound via adjusting the doping concentration or
      temperature. The occupancies of Ce3+ ions at two different sites (Wyckoff 6h and
      4f sites) in LiY9(SiO4)6O2 have been determined by Rietveld refinements. Two
      kinds of Ce3+ f-d transitions have been studied in detail and then assigned to
      certain sites. The effects of temperature and doping concentration on Ce3+
      luminescence properties have been systematically investigated. It is found that
      the Ce3+ ions prefer occupying Wyckoff 6h sites and the energy transfer between
      Ce3+ at two sites becomes more efficient with an increase in doping
      concentration. In addition, the charge-transfer vibronic exciton (CTVE) induced
      by the existence of free oxygen ion plays an important role in the thermal
      quenching of Ce3+ at 6h sites. Because of the tunable emissions from cyan to blue
      with increasing temperature, the phosphors LiY9(SiO4)6O2:Ce3+ are endowed with
      possible thermometric applications.

PMID- 27700070
TI  - Wasabisides A-E, Lignan Glycosides from the Roots of Wasabia japonica.
AB  - Five new lignan glycosides, wasabisides A-E (1-5), and four known phenolic
      compounds (6-9), were isolated from the roots of Wasabia japonica. The chemical
      structures of the new compounds (1-5) were determined through spectroscopic
      analysis and chemical methods. All isolated compounds (1-9) were evaluated for
      their potential neuroprotective effects through induction of nerve growth factor
      in C6 glioma cells, for their effects on nitric oxide levels in
      lipopolysaccharide-stimulated murine microglia BV2 cells, and for their
      cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and
      BT549).

PMID- 27700069
TI  - Environmental Chemicals in an Urban Population of Pregnant Women and Their
      Newborns from San Francisco.
AB  - Exposures to environmental pollutants in utero may increase the risk of adverse
      health effects. We measured the concentrations of 59 potentially harmful
      chemicals in 77 maternal and 65 paired umbilical cord blood samples collected in
      San Francisco during 2010-2011, including polychlorinated biphenyls (PCBs),
      organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs),
      hydroxylated PBDEs (OH-PBDEs), and perfluorinated compounds (PFCs) in serum and
      metals in whole blood. Consistent with previous studies, we found evidence that
      concentrations of mercury (Hg) and lower-brominated PBDEs were often higher in
      umbilical cord blood or serum than in maternal samples (median cord:maternal
      ratio > 1), while for most PFCs and lead (Pb), concentrations in cord blood or
      serum were generally equal to or lower than their maternal pair (median
      cord:maternal ratio <= 1). In contrast to the conclusions of a recent review, we
      found evidence that several PCBs and OCPs were also often higher in cord than
      maternal serum (median cord:maternal ratio > 1) when concentrations are assessed
      on a lipid-adjusted basis. Our findings suggest that for many chemicals, fetuses
      may experience higher exposures than their mothers and highlight the need to
      characterize potential health risks and inform policies aimed at reducing sources
      of exposure.

PMID- 27700072
TI  - Effect of Oral Administration of 3,3'-Diindolylmethane on Dextran Sodium Sulfate
      Induced Acute Colitis in Mice.
AB  - In patients with inflammatory bowel disease (IBD), inflammation is induced and
      maintained by lymphangiogenesis and angiogenesis. 3,3'-Diindolylmethane (DIM) is
      a natural product formed in acidic conditions from indole-3-carbinol in
      cruciferous vegetables, and it is known for its chemotherapeutic activity. This
      study evaluated DIM's effects on angiogenesis, lymphangiogenesis, and
      inflammation in a mouse colitis model. Experimental colitis was induced in mice
      by administering 3% dextran sulfate sodium (DSS) via drinking water. DIM
      remarkably attenuated the clinical signs and histological characteristics in mice
      with DSS-induced colitis. DIM suppressed neutrophil infiltration and pro
      inflammatory cytokines. Moreover, it significantly suppressed the expression of
      vascular endothelial growth factor (VEGF)-A and VEGF receptor (VEGFR)-2,
      indicating that the mechanism may be related to the repression of pro
      angiogenesis activity. DIM also remarkably suppressed the expression of VEGF-C,
      VEGF-D, VEGFR-3, and angiopoietin-2; thus, the mechanism may also be related to
      the suppression of lymphangiogenesis. Therefore, DIM is a possible treatment
      option for inflammation of the intestine and associated angiogenesis and
      lymphangiogenesis.

PMID- 27700073
TI  - Iterative Synthesis of Oligo[n]rotaxanes in Excellent Yield.
AB  - We present an operationally simple iterative coupling strategy for the synthesis
      of oligomeric homo- and hetero[n]rotaxanes with precise control over the position
      of each macrocycle. The exceptional yield of the AT-CuAAC reaction, combined with
      optimized conditions that allow the rapid synthesis of the target oligomers,
      opens the door to the study of precision-engineered oligomeric interlocked
      molecules.

PMID- 27700071
TI  - Biosynthetic Timing and Substrate Specificity for the Thiopeptide Thiomuracin.
AB  - The biosynthesis of the thiopeptide thiomuracin is a well-orchestrated process
      involving a multitude of posttranslational modifications. We show that six Cys
      residues of a precursor peptide are first cyclodehydrated and oxidized to
      thiazoles in an ordered, but nonlinear fashion that is leader-peptide-dependent.
      Then four alcohols are glutamylated and converted to alkenes in a C-to-N terminal
      directional process that is leader-peptide-independent. Finally, two of these
      alkenes undergo a formal [4 + 2] cycloaddition to form a trithiazole-substituted
      pyridine macrocycle. We describe here the factors that govern the substrate
      specificity and order of biosynthetic events that turn a ribosomal peptide into a
      powerful antibiotic.

PMID- 27700075
TI  - Optimized DNA "Nanosuitcases" for Encapsulation and Conditional Release of siRNA.
AB  - We set out to design, synthesize and optimize a DNA-minimal cage capable of
      encapsulating oligonucleotide drugs to facilitate their delivery. Through
      rational design and optimization using in vitro assays, we have assembled the
      first DNA "nanosuitcase" that can encapsulate a siRNA construct and release it
      upon recognition of an oligonucleotide trigger. The latter may be a messenger RNA
      (mRNA) or a microRNA (miRNA) which offers potential for dual or synergistic
      therapy. This construct assembles in near 100% yield, releases its cargo on
      demand and can sustain biological conditions. Moreover, we find that the DNA
      scaffold is able to protect its cargo against site-specific cleavage and nuclease
      degradation. Release of the cargo is performed with fixed cells using a FRET
      enabled construct imaged by confocal microscopy and reveals that the DNA cage
      remains responsive at the molecular level in a complex cellular environment. We
      foresee this construct will be able to address challenges in drug delivery, more
      specifically in non-toxic delivery and targeted release.

PMID- 27700074
TI  - The Quest for Converting Biorenewable Bifunctional alpha-Methylene-gamma
      butyrolactone into Degradable and Recyclable Polyester: Controlling Vinyl
      Addition/Ring-Opening/Cross-Linking Pathways.
AB  - alpha-Methylene-gamma-butyrolactone (MBL), a naturally occurring and biomass
      sourced bifunctional monomer, contains both a highly reactive exocyclic C?C bond
      and a highly stable five-membered gamma-butyrolactone ring. Thus, all previous
      work led to exclusive vinyl-addition polymerization (VAP) product P(MBL)VAP. Now,
      this work reverses this conventional chemoselectivity to enable the first ring
      opening polymerization (ROP) of MBL, thereby producing exclusively unsaturated
      polyester P(MBL)ROP with Mn up to 21.0 kg/mol. This elusive goal was achieved
      through uncovering the thermodynamic, catalytic, and processing conditions. A
      third reaction pathway has also been discovered, which is a crossover propagation
      between VAP and ROP processes, thus affording cross-linked polymer P(MBL)CLP. The
      formation of the three types of polymers, P(MBL)VAP, P(MBL)CLP, and P(MBL)ROP,
      can be readily controlled by adjusting the catalyst (La)/initiator (ROH) ratio,
      which is determined by the unique chemoselectivity of the La-X (X = OR, NR2, R)
      group. The resulting P(MBL)ROP is degradable and can be readily
      postfunctionalized into cross-linked or thiolated materials but, more remarkably,
      can also be fully recycled back to its monomer thermochemically. Computational
      studies provided the theoretical basis for, and a mechanistic understanding of,
      the three different polymerization processes and the origin of the
      chemoselectivity.

PMID- 27700076
TI  - Stereoselective Synthesis of Methylene Oxindoles via Palladium(II)-Catalyzed
      Intramolecular Cross-Coupling of Carbamoyl Chlorides.
AB  - We report a highly robust, general and stereoselective method for the synthesis
      of 3-(chloromethylene)oxindoles from alkyne-tethered carbamoyl chlorides using
      PdCl2(PhCN)2 as the catalyst. The transformation involves a stereo- and
      regioselective chloropalladation of an internal alkyne to generate a nucleophilic
      vinyl PdII species, which then undergoes an intramolecular cross-coupling with a
      carbamoyl chloride. The reaction proceeds under mild conditions, is insensitive
      to the presence of moisture and air, and is readily scalable. The products
      obtained from this reaction are formed with >95:5 Z:E selectivity in nearly all
      cases and can be used to access biologically relevant oxindole cores. Through
      combined experimental and computational studies, we provide insight into stereo-
      and regioselectivity of the chloropalladation step, as well as the mechanism for
      the C-C bond forming process. Calculations provide support for a mechanism
      involving oxidative addition into the carbamoyl chloride bond to generate a high
      valent PdIV species, which then undergoes facile C-C reductive elimination to
      form the final product. Overall, the transformation constitutes a formal PdII
      catalyzed intramolecular alkyne chlorocarbamoylation reaction.

PMID- 27700077
TI  - Semisynthesis and Structure-Activity Studies of Uncarinic Acid C Isolated from
      Uncaria rhynchophylla as a Specific Inhibitor of the Nucleation Phase in Amyloid
      beta42 Aggregation.
AB  - Oligomers of the 42-mer amyloid-beta protein (Abeta42), rather than fibrils,
      cause synaptic dysfunction in the pathology of Alzheimer's disease (AD). The
      nucleation phase in a nucleation-dependent aggregation model of Abeta42 is
      related to the formation of oligomers. Uncaria rhynchophylla is one component of
      "Yokukansan", a Kampo medicine, which is widely used for treating AD symptoms.
      Previously, an extract of U. rhynchophylla was found to reduce the aggregation of
      Abeta42, but its active principles have yet to be identified. In the present
      work, uncarinic acid C (3) was identified as an inhibitor of Abeta42 aggregation
      that is present in U. rhynchophylla. Moreover, compound 3 acted as a specific
      inhibitor of the nucleation phase of Abeta42 aggregation. Compound 3 was
      synthesized from saponin A (10), an abundant byproduct of rutin purified from
      Uncaria elliptica. Comprehensive structure-activity studies on 3 suggest that
      both a C-27 ferulate and a C-28 carboxylic acid group are required for its
      inhibitory activity. These findings may aid the development of oligomer-specific
      inhibitors for AD therapy.

PMID- 27700078
TI  - Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetes Mellitus.
AB  - The aim of the study was to analyze the possible neuroprotective effect of
      hydroxytyrosol (HT) in diabetic animals in a model of hypoxia-reoxygenation. Rats
      (10 animals/group) were distributed in five groups: nondiabetic rats, control
      diabetic rats (DR), and DR rats treated for 2 months with 1, 5, or 10 mg/kg/day
      po HT. At the end of follow-up, an experimental model of hypoxia-reoxygenation in
      brain slices was tested. The DR group showed increased cell death, oxidative and
      nitrosative stress, and an increase in brain inflammatory mediators. These
      alterations were significantly greater in DR than in normoglycemic animals. HT
      significantly reduced oxidative (38.5-52.4% lipid peroxidation) and nitrosative
      stress (48.0-51.0% nitric oxide and 43.9-75.2% peroxynitrite concentration) and
      brain inflammatory mediators (18.6-40.6% prostaglandin E2 and 17.0-65.0%
      interleukin 1beta concentration). Cell death was reduced by 25.9, 37.5, and 41.0%
      after the administration of 1, 5, or 10 mg/kg/day. The administration of HT in
      rats with experimental diabetes thus had a neuroprotective effect.

PMID- 27700079
TI  - Selective Catalytic Reduction of N2 to N2H4 by a Simple Fe Complex.
AB  - The catalytic fixation of N2 by molecular Fe compounds is a rapidly developing
      field, yet thus far few complexes can effect this transformation, and none are
      selective for N2H4 production. Herein we report that the simple Fe(0) complex
      Fe(Et2PCH2CH2PEt2)2(N2) (1) is an efficient catalyst for the selective conversion
      of N2 (>25 molecules N2 fixed) into N2H4, attendant with the production of ca.
      one molecule of NH3. Notably, the reductant (CoCp*2) and acid (Ph2NH2OTf) used
      are considerably weaker than conventional chemical H+ and e- sources used in
      previous demonstrations of N2 turnover by synthetic Fe compounds. These results
      show that the direct catalytic conversion of N2 to the hydrazine oxidation state
      on molecular Fe complexes is viable and that the mechanism of NH3 formation by
      such systems may proceed via Fe-N2H4 intermediates.

PMID- 27700080
TI  - A Mild Cu(I)-Catalyzed Oxidative Aromatization of Indolines to Indoles.
AB  - A novel method for the oxidation of indolines to indoles is described. The method
      uses a Cu(I) catalyst and an organic percarbonate as the stoichiometric oxidant.
      The procedure was successfully applied at 0.5 kg scale in the production of a key
      intermediate in the synthesis of Elbasvir, which is a novel therapy for the
      treatment of hepatitis C virus infection.

PMID- 27700081
TI  - Uncovering Single-Molecule Photophysical Heterogeneity of Bright, Thermally
      Activated Delayed Fluorescence Emitters Dispersed in Glassy Hosts.
AB  - Recently developed all-organic emitters used in display applications achieve high
      brightness by harvesting triplet populations via thermally activated delayed
      fluorescence. The photophysical properties of these emitters therefore involve
      new inherent complexities and are strongly affected by interactions with their
      host material in the solid state. Ensemble measurements occlude the molecular
      details of how host-guest interactions determine fundamental properties such as
      the essential balance of singlet oscillator strength and triplet harvesting.
      Therefore, using time-resolved fluorescence spectroscopy, we interrogate these
      emitters at the single-molecule level and compare their properties in two
      distinct glassy polymer hosts. We find that nonbonding interactions with aromatic
      moieties in the host appear to mediate the molecular configurations of the
      emitters, but also promote nonradiative quenching pathways. We also find
      substantial heterogeneity in the time-resolved photoluminescence of these
      emitters, which is dominated by static disorder in the polymer. Finally, since
      singlet-triplet cycling underpins the mechanism for increased brightness, we
      present the first room-temperature measurement of singlet-triplet equilibration
      dynamics in this family of emitters. Our observations present a molecular-scale
      interrogation of host-guest interactions in a disordered film, with implications
      for highly efficient organic light-emitting devices. Combining a single-molecule
      experimental technique with an emitter that is sensitive to triplet dynamics, yet
      read out via fluorescence, should also provide a complementary approach to
      performing fundamental studies of glassy materials over a large dynamic range of
      time scales.

PMID- 27700082
TI  - Difference in Energy between Two Distinct Types of Chalcogen Bonds Drives
      Regioisomerization of Binuclear (Diaminocarbene)PdII Complexes.
AB  - The reaction of cis-[PdCl2(CNXyl)2] (Xyl = 2,6-Me2C6H3) with various 1,3-thiazol-
      and 1,3,4-thiadiazol-2-amines in chloroform gives a mixture of two regioisomeric
      binuclear diaminocarbene complexes. For 1,3-thiazol-2-amines the isomeric ratio
      depends on the reaction conditions and kinetically (KRs) or thermodynamically
      (TRs) controlled regioisomers were obtained at room temperature and on heating,
      respectively. In CHCl3 solutions, the isomers are subject to reversible
      isomerization accompanied with the cleavage of Pd-N and S-N bonds in the carbene
      fragment XylNCN(R)Xyl. Results of DFT calculations followed by the topological
      analysis of the electron density distribution within the formalism of Bader's
      theory (AIM method) reveal that in CHCl3 solution the relative stability of the
      regioisomers (?Gexp = 1.2 kcal/mol; ?Gcalcd = 3.2 kcal/mol) is determined by the
      energy difference between two types of the intramolecular chalcogen bonds, viz.
      S***Cl in KRs (2.8-3.0 kcal/mol) and S***N in TRs (4.6-5.3 kcal/mol). In the case
      of the 1,3,4-thiadiazol-2-amines, the regioisomers are formed in approximately
      equal amounts and, accordingly, the energy difference between these species is
      only 0.1 kcal/mol in terms of ?Gexp (?Gcalcd = 2.1 kcal/mol). The regioisomers
      were characterized by elemental analyses (C, H, N), HRESI+-MS and FTIR, 1D (1H,
      13C) and 2D (1H,1H-COSY, 1H,1H-NOESY, 1H,13C-HSQC, 1H,13C-HMBC) NMR
      spectroscopies, and structures of six complexes (three KRs and three TRs) were
      elucidated by single-crystal X-ray diffraction.

PMID- 27700083
TI  - Tunable Visible and Near Infrared Photoswitches.
AB  - A class of tunable visible and near-infrared donor-acceptor Stenhouse adduct
      (DASA) photoswitches were efficiently synthesized in 2 to 4 steps from
      commercially available starting materials with minimal purification. Using either
      Meldrum's or barbituric acid "acceptors" in combination with aniline-based
      "donors" an absorption range spanning from 450 to 750 nm is obtained.
      Additionally, photoisomerization results in complete decoloration for all
      adducts, yielding fully transparent, colorless solutions and films. Detailed
      investigations using density functional theory, nuclear magnetic resonance, and
      visible absorption spectroscopies provide valuable insight into the unique
      structure-property relationships for this novel class of photoswitches. As a
      final demonstration, selective photochromism is accomplished in a variety of
      solvents and polymer matrices, a significant advantage for applications of this
      new generation of DASAs.

PMID- 27700084
TI  - Indium-Mediated Stereoselective Allylation.
AB  - Stereoselective indium-mediated organic reactions have enjoyed tremendous growth
      in the last 25 years. This is in part due to the insensitivity of allylindium to
      moisture, affording facile and practical reaction conditions coupled with
      outstanding functional group tolerance and minimal side reactions. Despite the
      plethora of articles about allylindium, there is much yet to be discovered and
      exploited for efficient and sustainable synthesis. In this Account, we describe
      indium-mediated synthetic methods for the preparation of chiral amines with the
      aim to present a balance of practical method development, novel asymmetric
      chemistry, and mechanistic understanding that impact multiple chemical and
      materials science disciplines. In 2005, we demonstrated the indium-mediated
      allylation of chiral hydrazones with complete diastereoselectivity (>99:1) and
      quantitative yields. Further, we revealed the first example of enantioselective
      indium-mediated allylation of hydrazones using catalytic (R)-3,3'
      bis(trifluoromethyl)-BINOL ligands to afford homoallylic amines with high
      enantioselectivity. The use of enantiopure perfluoroalkylsulfonate BINOLs greatly
      improved the indium-mediated allylation of N-acylhydrazones with exquisite
      enantiocontrol (99% yield, 99% ee). This laboratory has also investigated indium
      mediated asymmetric intramolecular cyclization in the presence of amino acid
      additives to deliver biologically relevant chromanes with excellent
      diastereoselectivity (dr >99:1). The effect of amino acid additives (N-Boc
      glycine) was further investigated during the indium-mediated allylation of
      isatins with allyl bromide to yield homoallylic alcohols in excellent yields in a
      short time with a wide range of functional group tolerance. Critical mechanistic
      insight was gained, and evidence suggests that the additive plays two roles: (1)
      to increase the rate of formation of allylindium from allyl bromide and In(0) and
      (2) to increase the nucleophilicity of the allylindium reagent, probably through
      disruption of aggregates and coordination to the metal. We recently reported the
      palladium-catalyzed umpolung allylation of hydrazones with allyl acetates in the
      presence of indium(I) iodide (InI) with excellent diastereoselectivity (up to
      99:1). The conversion was found to be inversely proportional to the phosphine
      concentration, providing insight into the mechanism of the critical redox
      transmetalation process that has implications for other Pd-catalyzed umpolung
      type allylation processes. A detailed overview of the work in our lab is
      presented with the intention of stimulating further research interest in
      organoindium chemistry and its application in organic synthesis.

PMID- 27700086
TI  - Microwave Spectra, Structure, and Ring-Puckering Vibration of
      Octafluorocyclopentene.
AB  - The rotational spectra of octafluorocyclopentene (C5F8) has been measured for the
      first time using pulsed jet Fourier transform microwave spectroscopy in a
      frequency range of 6 to 16 GHz. As in the molecule cyclopentene, the carbon ring
      is nonplanar, and inversion through the plane results in an inversion pair of
      ground state vibrational energy levels with an inversion splitting of 18.4 MHz.
      This large amplitude motion leads to the vibration-rotation coupling of energy
      levels. The symmetric double minimum ring-puckering potential function was
      calculated, resulting in a barrier of 222 cm-1. The rotational constants A0 =
      962.9590(1) MHz, B0 = 885.1643(4) MHz, C0 = 616.9523(4) MHz, A1 = 962.9590(1)
      MHz, B1 = 885.1643(4) MHz, C1 = 616.9528(4) MHz, and two centrifugal distortion
      constants for each state were determined for the parent species and all 13C
      isotopologues. A mixed coordinate molecular structure was determined from a least
      squares fit of the ground state rotational constants of the parent and each 13C
      isotopologue combined with the equilibrium bond lengths and angles from quantum
      chemical calculations.

PMID- 27700085
TI  - Effect of Conformers on Free Energies of Atmospheric Complexes.
AB  - In this article we show how to calculate free energies for atmospherically
      relevant complexes when multiple conformers and/or isomers are present. We
      explain why the thermal averaging methods used in several published works are
      incorrect. On the basis of our two sample cases, the sulfuric acid-pinic acid
      complex and the (H2SO4)3(NH3)3(H2O)4 cluster, we provide numerical evidence that
      the use of these incorrect formulas can result in errors larger than 1 kcal/mol.
      We recommend that if vibrational frequencies and thus Gibbs free energies of the
      individual conformers are unavailable, one should not attempt to correct for the
      presence of multiple conformers and instead use only the global minimum
      conformers for both reactants and products. On the contrary, if the free energies
      for the conformers are calculated for both reactants and products, their effect
      can be accounted for by the statistical mechanical methods presented in this
      article.

PMID- 27700087
TI  - How Does a Hydrophobic Macromolecule Respond to Mixed Osmolyte Environment?
AB  - The role of the protecting osmolyte Trimethyl N-oxide (TMAO) in counteracting the
      denaturing effect of urea on a protein is quite well established. However, the
      mechanistic role of osmolytes on the hydrophobic interaction underlying protein
      folding is a topic of contention and is emerging as a key area of biophysical
      interest. Although recent experiment and computer simulation have established
      that individual aqueous solution of TMAO and urea respectively stabilizes and
      destabilizes the collapsed conformation of a hydrophobic polymer, it remains to
      be explored how a mixed aqueous solution of protecting and denaturing osmolytes
      influences the conformations of the polymer. In order to bridge the gap, we have
      simulated the conformational behavior of both a model hydrophobic polymer and a
      synthetic polymer polystyrene in an aqueous mixture of TMAO and urea.
      Intriguingly, our free energy based simulations on both the systems show that
      even though a pure aqueous solution of TMAO stabilizes the collapsed or globular
      conformation of the hydrophobic polymer, addition of TMAO to an aqueous solution
      of urea further destabilizes the collapsed conformation of the hydrophobic
      polymer. We also observe that the extent of destabilization in a mixed osmolyte
      solution is relatively higher than that in pure aqueous urea solution. The
      reinforcement of the denaturation effect of the hydrophobic macromolecule in a
      mixed osmolyte solution is in stark contrast to the well-known counteracting role
      of TMAO in proteins under denaturing condition of urea. In both model and
      realistic systems, our results show that in a mixed aqueous solution, greater
      number of cosolutes preferentially bind to the extended conformation of the
      polymer relative to that in the collapsed conformation, thereby complying with
      Tanford-Wyman preferential solvation theory disfavoring the collapsed
      conformation. The results are robust across a range of osmolyte concentrations
      and multiple cosolute forcefields. Our findings unequivocally imply that the
      action of mixed osmolyte solution on hydrophobic polymer is significantly
      distinct from that of proteins.

PMID- 27700088
TI  - Classical and Quantum Shortcuts to Adiabaticity in a Tilted Piston.
AB  - Adiabatic quantum state evolution can be accelerated through a variety of
      shortcuts to adiabaticity. In one approach, a counterdiabatic quantum
      Hamiltonian, HCD, is constructed to suppress nonadiabatic excitations. In the
      analogous classical problem, a counterdiabatic classical Hamiltonian, HCD,
      ensures that the classical action remains constant even under rapid driving. Both
      the quantum and classical versions of this problem have been solved for the
      special case of scale-invariant driving, characterized by linear expansions,
      contractions, or translations of the system. Here we investigate an example of a
      non-scale-invariant system, a tilted piston. We solve exactly for the classical
      counterdiabatic Hamiltonian, HCD(q, p, t), which we then quantize to obtain a
      Hermitian operator, HCD(t). Using numerical simulations, we find that HCD
      effectively suppresses nonadiabatic excitations under rapid driving. These
      results offer a proof of principle, beyond the special case of scale-invariant
      driving, that quantum shortcuts to adiabaticity can successfully be constructed
      from their classical counterparts.

PMID- 27700089
TI  - New Melting Data of the Two Polymorphs of Prednisolone.
AB  - Prednisolone is known to exist in two anhydrous solid polymorphic forms. The
      substance is known to degrade upon melting, resulting in erroneous melting data,
      as shown by the widely scattered results reported in the literature. In this
      article, thermal analyses carried out at different scan rates show that the onset
      temperature and the enthalpy value of the signal increase with the scan rate and
      reach plateau values for high scan rates. Owing to flash scanning calorimetry,
      the plateau value for the temperature has been identified as the "true"
      temperature of melting of both polymorphs. This consistent set of new
      thermodynamic data on the two solid forms leads to the conclusion that both forms
      are unambiguously enantiotropes of each other. The solid-solid transition has
      been observed experimentally for the first time and has been confirmed by
      calculation.

PMID- 27700090
TI  - Benchmark Thermodynamic Properties of Methyl- and Methoxy-Benzamides:
      Comprehensive Experimental and Theoretical Study.
AB  - The enthalpies of formation of 2-, 3-, and 4-CH3-benzamide, as well as for 2-CH3O
      benzamide were measured by using combustion calorimetry. Vapor pressures of the
      isomeric CH3- and CH3O-benzamides were measured by using the transpiration
      method. The enthalpies of sublimation/vaporization of these compounds at 298 K
      were obtained from temperature dependencies of vapor pressures. The enthalpies of
      solution of the isomeric CH3- and CH3O-benzamides were measured with solution
      calorimetry. The enthalpies of sublimation of m- and p-substituted benzamides
      were independently derived with help of a solution calorimetry based procedure.
      The enthalpies of fusion of the CH3-benzamides were derived from DSC
      measurements. Thermochemical data on CH3- and CH3O-benzamides were collected,
      evaluated, and tested for internal consistency. A simple incremental procedure
      has been suggested for a quick appraisal of vaporization enthalpies of
      substituted benzamides. The high-level G4 quantum-chemical method was used for
      mutual validation of the experimental and theoretical gas phase enthalpies of
      formation. A remarkable ability of the G4 based atomization procedure to
      calculate reliable enthalpies of formation has been established for the set of
      aliphatic and aromatic amides. An outlook for the proper validation of the G4-AT
      procedure was discussed.

PMID- 27700091
TI  - Theoretical Study on Effects of Hydrogen-Bonding and Molecule-Cation Interactions
      on the Sensitivity of HMX.
AB  - To assess the effects of weak interactions on the sensitivity of HMX, eleven
      complexes of HMX (where six of them are hydrogen-bonding complexes, and the other
      five are molecular-cation complexes) have been studied via quantum chemical
      treatment. The geometric and electronic structures were determined using DFT
      B3LYP and MP2(full) methods with the 6-311++G(2df, 2p) and aug-cc-pVTZ basis
      sets. The changes of the bond dissociation energy (BDE) of the trigger bond (N
      NO2 in HMX) and nitro group charge have been computed on the detail consideration
      to access the sensitivity changes of HMX. The results indicate that upon complex
      forming, the BDE increases and the charge of nitro group turns more negative in
      complexes, suggesting that the strength of the N-NO2 trigger bond is enhanced
      then the sensitivity of HMX is reduced. Atom-in-molecules analysis have also been
      carried to understand the nature of intermolecular interactions and the strength
      of trigger bonds.

PMID- 27700092
TI  - An Automated Pipeline to Monitor System Performance in Liquid Chromatography
      Tandem Mass Spectrometry Proteomic Experiments.
AB  - We report the development of a completely automated pipeline to monitor system
      suitability in bottom-up proteomic experiments. LC-MS/MS runs are automatically
      imported into Skyline and multiple identification-free metrics are extracted from
      targeted peptides. These data are then uploaded to the Panorama Skyline document
      repository where metrics can be viewed in a web-based interface using powerful
      process control techniques, including Levey-Jennings and Pareto plots. The
      interface is versatile and takes user input, which allows the user significant
      control over the visualization of the data. The pipeline is vendor and instrument
      type neutral, supports multiple acquisition techniques (e.g., MS 1 filtering,
      data-independent acquisition, parallel reaction monitoring, and selected reaction
      monitoring), can track performance of multiple instruments, and requires no
      manual intervention aside from initial setup. Data can be viewed from any
      computer with Internet access and a web browser, facilitating sharing of QC data
      between researchers. Herein, we describe the use of this pipeline, termed
      Panorama AutoQC, to evaluate LC-MS/MS performance in a range of scenarios
      including identification of suboptimal instrument performance, evaluation of
      ultrahigh pressure chromatography, and identification of the major sources of
      variation throughout years of peptide data collection.

PMID- 27700093
TI  - Highly Efficient Free Energy Calculations of the Fe Equation of State Using
      Temperature-Dependent Effective Potential Method.
AB  - Free energy calculations at finite temperature based on ab initio molecular
      dynamics (AIMD) simulations have become possible, but they are still highly
      computationally demanding. Besides, achieving simultaneously high accuracy of the
      calculated results and efficiency of the computational algorithm is still a
      challenge. In this work we describe an efficient algorithm to determine accurate
      free energies of solids in simulations using the recently proposed temperature
      dependent effective potential method (TDEP). We provide a detailed analysis of
      numerical approximations employed in the TDEP algorithm. We show that for a model
      system considered in this work, hcp Fe, the obtained thermal equation of state at
      2000 K is in excellent agreement with the results of standard calculations within
      the quasiharmonic approximation.

PMID- 27700094
TI  - The Molecular Origin of Ultrafast Water-Protein Coupled Interactions.
AB  - The fluctuations of hydration water and the protein are coupled together at the
      protein surface and often such water-protein dynamic interactions are controlled
      presumably by hydration water motions. However, direct evidence is scarce and it
      requires measuring the dynamics of hydration water and protein sidechain
      simultaneously. Here, we use a unique protein with a single tryptophan to
      directly probe interfacial water and related sidechain relaxations with
      temperature dependence. With systematic mutations to change local chemical
      identity and structural flexibility, we found that the sidechain relaxations are
      always slower than hydration water motions and the two dynamic processes are
      linearly correlated with the same energy barriers, indicating the same origin of
      both relaxations. The charge mutations change the rates of hydration water
      relaxations but not the relaxation barriers. These results convincingly show that
      the water-protein relaxations are strongly coupled and the hydration water
      molecules govern such fluctuations on the picosecond timescales.

PMID- 27700095
TI  - Halogen Bonding with Phosphine: Evidence for Mulliken Inner Complexes and the
      Importance of Relaxation Energy.
AB  - Intermolecular halogen bonding in complexes of phosphine and dihalogens has been
      theoretically investigated using explicitly correlated coupled cluster methods
      and symmetry adapted perturbation theory. The complexes H3P. . . ClF, H3P. . .
      BrF and H3P. . . IF are demonstrated to possess unusually strong interactions
      that are accompanied by an increase in the induction component of the interaction
      energy and significant elongation of the X-Y halogen distance on complex
      formation. The combination of these factors is indicative of Mulliken inner
      complexes and criteria for identifying this classification are further developed.
      The importance of choosing an electronic structure method that describes both
      dispersion and longer range interactions is demonstrated, along with the need to
      account for the change in geometry on complexation formation via relaxation
      energy and overall stabilisation energies.

PMID- 27700096
TI  - Homo- and Stereocomplex Crystallization of Star-Shaped Four-Armed Stereo Diblock
      Copolymers of Crystalline and Amorphous Poly(lactide)s: Effects of Incorporation
      and Position of Amorphous Blocks.
AB  - Star-shaped four-armed stereo diblock copolymers with an amorphous poly(DL
      lactide) (PDLLA) core and a crystalline poly(L-lactide) (PLLA) or poly(D-lactide)
      (PDLA) shell (4-DL-L and 4-DL-D) and with a crystalline PLLA or PDLA core and
      amorphous PDLLA shell (4-L-DL and 4-D-DL) copolymers were synthesized. The
      effects of incorporation and position of amorphous PDLLA blocks on homo- and
      stereocomplex (SC) crystallization behavior of unblended copolymers and their
      blends (4-DL-L/4-DL-D and 4-L-DL/4-D-DL) were investigated during isothermal
      crystallization from the melt and DSC heating. The incorporated amorphous PDLLA
      blocks disturbed the SC crystallization and orientation of SC lamellae in the
      copolymer blends as well as homo-crystallization and orientation of homo
      crystalline lamellae of the unblended copolymers compared to those reported for
      four-armed PLLA homopolymers or four-armed PLLA/four-armed PDLA homopolymer
      blends, irrespective of the position of amorphous PDLLA blocks. The disturbance
      effect was stronger for the amorphous PDLLA shell than for the amorphous PDLLA
      core. The crystallizability was higher for SC crystallites in the copolymer
      blends than for homo-crystallites in the unblended copolymers, irrespective of
      the position of amorphous PDLLA blocks. SC crystallization in the copolymer
      blends disclaimed the positional effects of crystalline PLLA and PDLA blocks and
      amorphous PDLLA blocks on spherulite growth rate and crystallinity.

PMID- 27700097
TI  - Nanoscale Density Fluctuations in Ionic Liquid Binary Mixtures with
      Nonamphiphilic Compounds: First Experimental Evidence.
AB  - A complex mesoscopic organization is observed in systems containing ethylammonium
      nitrate (EAN) and two nonamphiphilic compounds, using wide and small angle X-ray
      scattering and molecular dynamics simulations. The macroscopically homogeneous
      mixtures exhibit a separation where an ionic liquid-rich region is percolating a
      molecular liquid-rich one, but no unmixing is observed. This effect was already
      reported in EAN-alcohol mixtures, but the models proposed so far cannot explain
      this behavior for a nonamphiphilic compound.

PMID- 27700098
TI  - Multi-Shape and Temperature Memory Effects via Strong Physical Confinement in
      Poly(Propylene Carbonate)/Graphene Oxide Nanocomposites.
AB  - The importance of filler-matrix interactions is generally recognized for
      mechanical property enhancement, their direct impact via physical confinement on
      diverse functional properties has remained poorly explored. We report here our
      effort in achieving versatile shape memory performances for a biodegradable
      poly(propylene carbonate) (PPC) matrix containing high contents of graphene oxide
      (GO). The excellent dispersion in the entire filler range (up to 20 wt%) allows
      precise morphological tuning, along with the physical filler-matrix interactions,
      contributing overall to a strong nano-confinement effect that positively affects
      the thermo-mechanical properties of nanocomposites. Only one glass transition
      temperature (Tg) of PPC is detected as GO content is below 10 wt%, corresponding
      to a slightly confined system, whereas two distinct Tgs are observed with GO
      content over 10 wt%, corresponding to a highly confined system. As such, tunable
      multi-shape memory effect can be achieved simply by tuning the filler contents.
      Dual shape memory effect (SME) is observed for slightly confined system, while a
      triple SME can be achieved via deformation at two distinct Tgs for highly
      confined system. More importantly, it is interesting to find that the switch
      temperature (Tsw) evolves linearly with the programing temperature (Tprog) for
      both slightly and highly confined system, with Tsw ~ Tprog for highly confined
      system, but Tsw < Tprog for slightly confined system. Our work suggests a highly
      flexible approach to take advantage of strong nano-confinement effect via tuning
      the content of GO within a single polymer to access versatile SME, such as dual,
      triple shape memory and temperature memory effect.

PMID- 27700099
TI  - Organic Acids Regulation of Chemical-Microbial Phosphorus Transformations in
      Soils.
AB  - We have used an integrated approach to study the mobility of inorganic phosphorus
      (P) from soil solid phase as well as the microbial biomass P and respiration at
      increasing doses of citric and oxalic acid in two different soils with
      contrasting agronomic P status. Citric or oxalic acids significantly increased
      soil solution P concentrations for doses over 2 mmol kg-1. However, low organic
      acid doses (<2 mmol kg-1) were associated with a steep increase in microbial
      biomass P, which was not seen for higher doses. In both soils, treatment with the
      tribasic citric acid led to a greater increase in soil solution P than the
      dibasic oxalic acid, likely due to the rapid degrading of oxalic acids in soils.
      After equilibration of soils with citric or oxalic acids, the adsorbed-to
      solution distribution coefficient (Kd) and desorption rate constants (k-1)
      decreased whereas an increase in the response time of solution P equilibration
      (Tc) was observed. The extent of this effect was shown to be both soil and
      organic acid specific. Our results illustrate the critical thresholds of organic
      acid concentration necessary to mobilize sorbed and precipitated P, bringing new
      insight on how the exudation of organic acids regulate chemical-microbial soil
      phosphorus transformations.

PMID- 27700101
TI  - Layer-by-Layer Sorting of Rhenium Disulfide via High-Density Isopycnic Density
      Gradient Ultracentrifugation.
AB  - Isopycnic density gradient ultracentrifugation (iDGU) has been widely applied to
      sort nanomaterials by their physical and electronic structure. However, the
      commonly used density-gradient medium iodixanol has a finite maximum buoyant
      density that prevents the use of iDGU for high-density nanomaterials. Here, we
      overcome this limit by adding cesium chloride (CsCl) to iodixanol, thus
      increasing its maximum buoyant density to the point where the high-density two
      dimensional nanomaterial rhenium disulfide (ReS2) can be sorted in a layer-by
      layer manner with iDGU. The resulting aqueous ReS2 dispersions show
      photoluminescence at ~1.5 eV, which is consistent with its direct bandgap
      semiconductor electronic structure. Furthermore, photocurrent measurements on
      thin films formed from solution-processed ReS2 show a spectral response that is
      consistent with optical absorbance and photoluminescence data. In addition to
      providing a pathway for effective solution processing of ReS2, this work
      establishes a general methodology for sorting high-density nanomaterials via
      iDGU.

PMID- 27700102
TI  - Modulation of Low-Frequency Acoustic Vibrations in Semiconductor Nanocrystals
      through Choice of Surface Ligand.
AB  - Recent experimental and theoretical results have highlighted the surprisingly
      dominant role of acoustic phonons in regulating dynamic processes in
      nanocrystals. While it has been known for many years that acoustic phonon
      frequencies in nanocrystals depend on their size, strategies for tuning acoustic
      phonon energy at a given fixed size were not available. Here, we show that
      acoustic phonon frequencies in colloidal quantum dots (QDs) can be tuned through
      choice of the surface ligand. Using low-frequency Raman spectroscopy, we explore
      the dependence of the l = 0 acoustic phonon resonance in CdSe QDs on ligand size,
      molecular weight, and chemical functionality. Based on these aggregated
      observations, we conclude that the primary mechanism for this effect is mass
      loading of the QD surface, and that interactions between ligands and with the
      surrounding environment play a comparatively minor yet non-negligible role.

PMID- 27700100
TI  - Proteolysis by Granzyme B Enhances Presentation of Autoantigenic Peptidylarginine
      Deiminase 4 Epitopes in Rheumatoid Arthritis.
AB  - Proteolysis of autoantigens can alter normal MHC class II antigen processing and
      has been implicated in the induction of autoimmune diseases. Many autoantigens
      are substrates for the protease granzyme B (GrB), but the mechanistic
      significance of this association is unknown. Peptidylarginine deiminase 4 (PAD4)
      is a frequent target of autoantibodies in patients with rheumatoid arthritis (RA)
      and a substrate for GrB. RA is strongly associated with specific MHC class II
      alleles, and elevated levels of GrB and PAD4 are found in the joints of RA
      patients, suggesting that GrB may alter the presentation of PAD4 by RA-associated
      class II alleles. In this study, complementary proteomic and immunologic
      approaches were utilized to define the effects of GrB cleavage on the structure,
      processing, and immunogenicity of PAD4. Hydrogen-deuterium exchange and a cell
      free MHC class II antigen processing system revealed that proteolysis of PAD4 by
      GrB induced discrete structural changes in PAD4 that promoted enhanced
      presentation of several immunogenic peptides capable of stimulating PAD4-specific
      CD4+ T cells from patients with RA. This work demonstrates the existence of PAD4
      specific T cells in patients with RA and supports a mechanistic role for GrB in
      enhancing the presentation of autoantigenic CD4+ T cell epitopes.

PMID- 27700103
TI  - Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate
      Cancer.
AB  - There is a demand for novel targets and approaches to diagnose and treat prostate
      cancer (PCA). In this context, serum and plasma samples from a total of 609
      individuals from two independent patient cohorts were screened for IgG reactivity
      against a sum of 3833 human protein fragments. Starting from planar protein
      arrays with 3786 protein fragments to screen 80 patients with and without PCA
      diagnosis, 161 fragments (4%) were chosen for further analysis based on their
      reactivity profiles. Adding 71 antigens from literature, the selection of
      antigens was corroborated for their reactivity in a set of 550 samples using
      suspension bead arrays. The antigens prostein (SLC45A3), TATA-box binding protein
      (TBP), and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) showed
      higher reactivity in PCA patients with late disease compared with early disease.
      Because of its prostate tissue specificity, we focused on prostein and continued
      with mapping epitopes of the 66-mer protein fragment using patient samples. Using
      bead-based assays and 15-mer peptides, a minimal peptide epitope was identified
      and refined by alanine scanning to the KPxAPFP. Further sequence alignment of
      this motif revealed homology to transmembrane protein 79 (TMEM79) and TGF-beta
      induced factor 2 (TGIF2), thus providing a reasoning for cross-reactivity found
      in females. A comprehensive workflow to discover and validate IgG reactivity
      against prostein and homologous targets in human serum and plasma was applied.
      This study provides useful information when searching for novel biomarkers or
      drug targets that are guided by the reactivity of the immune system against
      autoantigens.

PMID- 27700106
TI  - Micropatterning of Phase-Segregated Supported Lipid Bilayers and Binary Lipid
      Phases through Polymer Stencil Lift-Off.
AB  - Supported lipid bilayers (SLBs) provide an excellent model system for studying
      structural and functional characteristics of biomembranes. Patterning model
      membranes on solid supports has elicited much interest because lipid bilayer
      arrays at cellular or sub-cellular scales provide attractive platforms for
      reconstituting tissue-like conditions for cell culture, and for creating
      simplified physiological environments to study biological processes. Phase
      segregated SLB patterns can be especially useful for such studies, as the
      selective functionalization of the lipid phases with different lipids, receptors
      or proteins can be achieved to mimic the key features of plasma membrane.
      However, it remains challenging to pattern phase-segregated lipid bilayers and to
      spatially control the lipid phases at the micron scale. Current methods to
      achieve this involve multiple surface modification and patterning steps,
      elaborate techniques such as microfluidic, microcontact printing, or
      electrochemical control, among others. To overcome the complexity in producing
      phase-segregated patterns, we have developed simple and rapid strategies to
      pattern SLBs with phase separation utilizing the polymer stencil lift-off (PSLO)
      technique. PSLO is a powerful technique for SLB patterning, since it allows the
      faithful pattern transfer of micron-sized lipid domains onto solid surfaces under
      aqueous conditions, which eliminates the need for controlled humidity and reduces
      the risk of bilayer disruption through drying. By integrating post-etching
      substrate cleaning and a blocking treatment, well-defined homogeneous and phase
      segregated SLB patterns were achieved with lipid mobility that matches that of
      SLBs formed on clean SiO2 wafer substrates. A two-step incubation method was also
      developed for patterning binary lipid phases, which allowed precise control of
      their position and geometries. The created phase-segregated SLB patterns were
      used to study lipid phase behavior within confined areas, and quantitative
      analysis showed that smaller pattern sizes resulted in smaller gel phase domains,
      which also covered a smaller fraction of the total patterned SLB area. This was
      attributed to the decreased mobility of the bottom leaflet of the SLB which lies
      in close proximity to the substrate, and the resulting hindered exchange of lipid
      molecules between the bottom and upper leaflets through the SLB boundary. By
      further integration with functional groups, the phase-segregated lipid bilayer
      patterns might find relevant application in tissue engineering, biophysical
      studies of biomolecular and cellular interactions, and biosensing platforms.

PMID- 27700104
TI  - Structural Attributes and Photodynamics of Visible Spectrum Quantum Emitters in
      Hexagonal Boron Nitride.
AB  - Newly discovered van der Waals materials like MoS2, WSe2, hexagonal boron nitride
      (h-BN), and recently C2N have sparked intensive research to unveil the quantum
      behavior associated with their 2D structure. Of great interest are 2D materials
      that host single quantum emitters. h-BN, with a band gap of 5.95 eV, has been
      shown to host single quantum emitters which are stable at room temperature in the
      UV and visible spectral range. In this paper we investigate correlations between
      h-BN structural features and emitter location from bulk down to the monolayer at
      room temperature. We demonstrate that chemical etching and ion irradiation can
      generate emitters in h-BN. We analyze the emitters' spectral features and show
      that they are dominated by the interaction of their electronic transition with a
      single Raman active mode of h-BN. Photodynamics analysis reveals diverse rates
      between the electronic states of the emitter. The emitters show excellent photo
      stability even under ambient conditions and in monolayers. Comparing the
      excitation polarization between different emitters unveils a connection between
      defect orientation and the h-BN hexagonal structure. The sharp spectral features,
      color diversity, room-temperature stability, long-lived metastable states, ease
      of fabrication, proximity of the emitters to the environment, outstanding
      chemical stability, and biocompatibility of h-BN provide a completely new class
      of systems that can be used for sensing and quantum photonics applications.

PMID- 27700105
TI  - Screening for Ricinoleic Acid as a Chemical Marker for Secale cornutum in Rye by
      High-Performance Thin-Layer Chromatography with Fluorescence Detection.
AB  - Ricinoleic acid as the characteristic fatty acid of Secale cornutum oil is a good
      marker for Secale cornutum impurities in cereal. The presented screening for
      ricinoleic acid in rye by high-performance thin-layer chromatography with
      fluorescence detection (HPTLC-FLD) offers a selective and sensitive method for
      the determination of Secale cornutum and is very different from existing gas
      chromatographic analyses. Lipid extraction was followed by transesterification
      and solid-phase extraction cleanup; thereafter, extracts were selectively
      derivatized with 2-naphthoyl chloride and analyzed by HPTLC-FLD with silica gel
      plates and cyclohexane/diisopropyl ether/formic acid (86:14:1, v/v/v) as mobile
      phase. For quantitation, the enhanced fluorescence was scanned at 280/>340 nm.
      Limits of detection and quantitation of 0.1 and 0.4 mg ricinoleic acid/kg of rye
      were obtained, which enables the determination of Secale cornutum far below the
      maximum admitted level. With near-100% recoveries and low standard deviations at
      relevant spiking levels, reliable results were guaranteed.

PMID- 27700107
TI  - Total Synthesis of Luotonin A and Rutaecarpine from an Aldimine via the Designed
      Cyclization.
AB  - The total synthesis of rutaecarpine (1) and luotonin A (2) is described through
      controlled cyclization of a common aldimine intermediate 5 derived from ethyl-2
      aminocinnamate and quinazolinone-2-carbaldehyde. The cyanide-mediated imino
      Stetter reaction of aldimine 5 provided the corresponding indole derivative 3,
      from which the total synthesis of rutaecarpine (1) was completed via the
      formation of a 6-membered C-ring. On the other hand, microwave-assisted thermal
      6pi-electrocyclization of the common intermediate 5, followed by the formation of
      a 5-membered C'-ring, allowed the completion of the total synthesis of luotonin A
      (2).

PMID- 27700108
TI  - Toward Single Electron Nanoelectronics Using Self-Assembled DNA Structure.
AB  - DNA based structures offer an adaptable and robust way to develop customized
      nanostructures for various purposes in bionanotechnology. One main aim in this
      field is to develop a DNA nanobreadboard for a controllable attachment of
      nanoparticles or biomolecules to form specific nanoelectronic devices. Here we
      conjugate three gold nanoparticles on a defined size TX-tile assembly into a
      linear pattern to form nanometer scale isolated islands that could be utilized in
      a room temperature single electron transistor. To demonstrate this, conjugated
      structures were trapped using dielectrophoresis for current-voltage
      characterization. After trapping only high resistance behavior was observed.
      However, after extending the islands by chemical growth of gold, several
      structures exhibited Coulomb blockade behavior from 4.2 K up to room temperature,
      which gives a good indication that self-assembled DNA structures could be used
      for nanoelectronic patterning and single electron devices.

PMID- 27700109
TI  - Investigating the Correlation between Miscibility and Physical Stability of
      Amorphous Solid Dispersions Using Fluorescence-Based Techniques.
AB  - The purpose of this study was to investigate the feasibility of using a
      fluorescence-based technique to evaluate drug-polymer miscibility and to probe
      the correlation between miscibility and physical stability of amorphous solid
      dispersions (ASDs). Indomethacin-hydroxypropyl methylcellulose (IDM-HPMC),
      indomethacin-hydroxypropyl methylcellulose acetate succinate, and indomethacin
      polyvinylpyrrolidone (IDM-PVP) were used as model systems. The miscibility of the
      IDM-polymer systems was evaluated by fluorescence spectroscopy, fluorescence
      imaging, differential scanning calorimetry (DSC), and infrared (IR) spectroscopy.
      The physical stability of IDM-polymer ASDs stored at 40  degrees C was evaluated
      using fluorescence imaging and X-ray diffraction (XRD). The experimentally
      determined miscibility limit of IDM with the polymers was 50-60%, 20-30%, and 70
      80% drug loading for HPMC, HPMCAS, and PVP, respectively. The X-ray results
      showed that for IDM-HPMC ASDs, samples with a drug loading of less than 50% were
      maintained in amorphous form during the study period, while samples with drug
      loadings higher than 50% crystallized within 15 days. For IDM-HPMCAS ASDs,
      samples with drug loading less than 30% remained amorphous, while samples with
      drug loadings higher than 30% crystallized within 10 days. IDM-PVP ASDs were
      found to be resistant to crystallization for all compositions. Thus, a good
      correlation was observed between phase separation and reduced physical stability,
      suggesting that miscibility is indeed an important ASDs characteristic. In
      addition, fluorescence-based techniques show promise in the evaluation of drug
      polymer miscibility.

PMID- 27700110
TI  - Single Gold Nanorod Charge Modulation in an Ion Gel Device.
AB  - A reliable and reproducible method to rapidly charge single gold nanocrystals in
      a solid-state device is reported. Gold nanorods (Au NRs) were integrated into an
      ion gel capacitor, enabling them to be charged in a transparent and highly
      capacitive device, ideal for optical transmission. Changes in the electron
      concentration of a single Au NR were observed with dark-field imaging
      spectroscopy via localized surface plasmon resonance (LSPR) shifts in the
      scattering spectrum. A time-resolved, laser-illuminated, dark-field system was
      developed to enable direct measurement of single particle charging rates with
      time resolution below one millisecond. The added sensitivity of this new approach
      has enabled the optical detection of fewer than 110 electrons on a single Au NR.
      Single wavelength resonance shifts provide a much faster, more sensitive method
      for all surface plasmon-based sensing applications.

PMID- 27700111
TI  - Transpapillary (Nipple) Delivery of Macromolecules to the Breast: Proof of
      Concept Study.
AB  - Localized drug delivery to the breast can maximize drug concentration at the
      target site and minimize systemic drug distribution. To this end, the study
      explored the feasibility of delivering macromolecules to the breast through
      mammary papilla (nipple). The in vitro penetration of model macromolecules
      (inulin, dextran, ovalbumin, and bovine serum albumin) varying in molecular
      weight from 5 to 67 kDa was studied using excised porcine and human mammary
      papilla. The penetration of macromolecules decreased with increase in molecular
      weight. The penetration of the macromolecules was significantly higher through
      the mammary papilla in comparison to breast skin. In vitro penetration of the
      macromolecules was similar in human and porcine mammary papilla. Iontophoresis
      was used to enhance the transport of bovine serum albumin (BSA) through the
      mammary papilla. The flux and cumulative amount permeated was increased by 2- to
      4-fold by iontophoresis. The macromolecules were transported through the ducts
      and the surrounding connective tissue in the mammary papilla. Overall, the
      results from this study for the first time demonstrate the feasibility of
      delivering macromolecules through the mammary papilla. These findings have
      implications for developing safe and effective localized therapeutic approaches
      for breast cancer.

PMID- 27700112
TI  - Physicochemical and Preclinical Evaluation of Spermine-Derived Surfactant
      Liposomes for in Vitro and in Vivo siRNA-Delivery to Liver Macrophages.
AB  - Herein we report on a liposomal system for siRNA delivery consisting of
      cholesterol (Chol), distearoylphosphatidylcholine (DSPC), and surfactant TF (1
      hydroxy-50-amino-3,4,7,10,13,16,19,22-octaoxa-37,41,45-triaza-pentacontane), a
      novel spermine derivative (HO-EG8-C12-spermine) which has shown improved siRNA
      delivery to cells in vitro and in vivo. Predominantly single-walled liposomes
      with reproducible sizes and moderately broad size distributions were generated
      with an automated extrusion device. The liposomes remained stable when prepared
      in the presence of siRNA at N/P ratios of 17-34. However, when mixed with human
      serum in equal volumes, larger aggregates in the size range of several hundred
      nanometers were observed by dynamic light scattering. These larger aggregates
      could potentially limit prolonged in vivo applications. Aggregate formation could
      be reduced by the addition of a cholesterol-hyperbranched polyglycerol surfactant
      (hbPG) that sterically shields the liposomal surface against serum induced
      aggregation. In vitro experiments with murine macrophages utilizing macrophage
      specific anti-CD68 siRNA loaded liposomes showed potent and sequence specific
      reduction of CD68 transcript levels without cytotoxicity. Experiments in mice
      using intravenous application of CW800 NHS ester labeled liposomes, near-infrared
      in vivo imaging, and fluorescent assisted cell sorting of inflammatory cells
      demonstrated an almost quantitative accumulation of these liposomes, with and
      without hbPG, in the liver and a specific knockdown of CD68 mRNA of up to 70% in
      liver resident macrophages. It was found that aggregate formation of TF liposomes
      in serum does not significantly affect in vivo siRNA delivery to these central
      inflammatory cells of the liver.

PMID- 27700114
TI  - Microcapsule Buckling Triggered by Compression-Induced Interfacial Phase Change.
AB  - There is an emerging trend towards the fabrication of microcapsules at liquid
      interfaces. In order to control the parameters of such capsules, the interfacial
      processes governing their formation must be understood. Here, poly(vinyl alcohol)
      films are assembled at the interface of water-in-oil microfluidic droplets. The
      polymer is cross-linked using cucurbit[8]uril ternary supramolecular complexes.
      It is shown that compression-induced phase change causes the onset of buckling in
      the interfacial film. On evaporative compression, the interfacial film both
      increases in density and thickens, until it reaches a critical density and a
      phase change occurs. We show that this increase in density can be simply related
      to the film Poisson ratio and area compression. This description captures
      fundamentals of many compressive interfacial phase changes and can also explain
      the observation of a fixed thickness-to-radius ratio at buckling, (T/R)buck.

PMID- 27700113
TI  - Resonance Coupling in Silicon Nanosphere-J-Aggregate Heterostructures.
AB  - Due to their optical magnetic and electric resonances associated with the high
      refractive index, dielectric silicon nanoparticles have been explored as novel
      nanocavities that are excellent candidates for enhancing various light-matter
      interactions at the nanoscale. Here, from both of theoretical and experimental
      aspects, we explored resonance coupling between excitons and magnetic/electric
      resonances in heterostructures composed of the silicon nanoparticle coated with a
      molecular J-aggregate shell. The resonance coupling was originated from coherent
      energy transfer between the exciton and magnetic/electric modes, which was
      manifested by quenching dips on the scattering spectrum due to formation of
      hybrid modes. The influences of various parameters, including the molecular
      oscillation strength, molecular absorption line width, molecular shell thickness,
      refractive index of the surrounding environment, and separation between the core
      and shell, on the resonance coupling behaviors were scrutinized. In particular,
      the resonance coupling can approach the strong coupling regime by choosing
      appropriate molecular parameters, where an anticrossing behavior with a mode
      splitting of 100 meV was observed on the energy diagram. Most interestingly, the
      hybrid modes in such dielectric heterostructure can exhibit unidirectional light
      scattering behaviors, which cannot be achieved by those in plexcitonic
      nanoparticle composed of a metal nanoparticle core and a molecular shell.

PMID- 27700115
TI  - Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues.
AB  - Mucus is a viscoelastic gel layer that typically protects exposed surfaces of the
      gastrointestinal (GI) tract, lung airways, and other mucosal tissues. Particles
      targeted to these tissues can be efficiently trapped and removed by mucus,
      thereby limiting the effectiveness of such drug delivery systems. In this study,
      we experimentally and theoretically demonstrated that cylindrical nanoparticles
      (NPs), such as mesoporous silica nanorods and calcium phosphate nanorods, have
      superior transport and trafficking capability in mucus compared with spheres of
      the same chemistry. The higher diffusivity of nanorods leads to deeper mucus
      penetration and a longer retention time in the GI tract than that of their
      spherical counterparts. Molecular simulations and stimulated emission of
      depletion (STED) microscopy revealed that this anomalous phenomenon can be
      attributed to the rotational dynamics of the NPs facilitated by the mucin fibers
      and the shear flow. These findings shed new light on the shape design of NP-based
      drug delivery systems targeted to mucosal and tumor sites that possess a fibrous
      structure/porous medium.

PMID- 27700116
TI  - Insights into drying of non-circular sessile nanofluid droplet towards multi
      scale surface patterning using a wall-less confinement architecture.
AB  - Surface patterning with functional colloids is an important research area due to
      its widespread applicability in domains ranging from nano-electronics,
      pharmaceutics, semi-conductors, photovoltaics among others. To this endeavour, we
      propose a low-cost patterning technique that aspires to eliminate the more
      expensive methodologies presently in practise. Using a simple document stamp on
      which patterns of any geometry can be embossed, we are able to print two
      dimensional mm-scale "wall-less confinement" using ink based hydrophobic fence on
      any plasma treated superhydrophilic surface. The confinement is subsequently
      filled with nanocolloidal liquid(s). Using the confinement geometry, we are able
      to control the 3D shape of the droplet to exhibit multiple interfacial
      curvatures. The droplet in the "wall-less confinements" evaporates naturally
      exhibiting unique geometry (curvature) induced flow structures which induce the
      nanoparticles to self-assemble into functional patterns. We have also shown that
      by modifying the geometry of the pattern, evaporation, flow and particle
      deposition dynamics get altered leading to precipitate topologies from macro to
      microscales. We, present two such geometrical designs which demonstrate the
      capability of modifying both the macroscopic as well as the microscopic features
      of the final precipitate. We have also provided a description of the physical
      mechanisms of the drying process by resolving the unique flow pattern using a
      combination of imaging and MUPIV (micro particle image velocimetry). These
      provide insights into the coupled dynamics of evaporation and flow responsible
      for the evolution of particle deposition pattern. Precipitate characterization
      using SEM and dark-field microscopy highlight the transformation in the deposit
      morphology.

PMID- 27700117
TI  - Iron-Mediated Domino Interrupted Iso-Nazarov/Dearomative (3 + 2)-Cycloaddition of
      Electrophilic Indoles.
AB  - An efficient domino reaction combining different classes of pericyclic reactions
      leads to chiral complex polycyclic indoline-based architectures from achiral
      starting materials under mild conditions. This practical method is based on the
      ability of iron(III) chloride to promote both 4pi electrocyclizations of 2,4
      dienals and the C2-C3 umpolung of N-acetylindoles during the dearomative (3 + 2)
      cycloadditions.

PMID- 27700118
TI  - Origin of pKa Shifts of Internal Lysine Residues in SNase Studied Via Equal-Molar
      VMMS Simulations in Explicit Water.
AB  - Protein internal ionizable groups can exhibit large shifts in pKa values.
      Although the environment and interaction changes have been extensively studied
      both experimentally and computationally, direct calculation of pKa values of
      these internal ionizable groups in explicit water is challenging due to energy
      barriers in solvent interaction and in conformational transition. The virtual
      mixture of multiple states (VMMS) method is a new approach designed to study
      chemical state equilibrium. This method constructs a virtual mixture of multiple
      chemical states in order to sample the conformational space of all states
      simultaneously and to avoid crossing energy barriers related to state transition.
      By applying VMMS to 25 variants of staphylococcal nuclease with lysine residues
      at internal positions, we obtained the pKa values of these lysine residues and
      investigated the physics underlining the pKa shifts. Our calculation results
      agree reasonably well with experimental measurements, validating the VMMS method
      for pKa calculation and providing molecular details of the protonation
      equilibrium for protein internal ionizable groups. Based on our analyses of
      protein conformation relaxation, lysine side chain flexibility, water
      penetration, and the microenvironment, we conclude that the hydrophobicity of the
      microenvironment around the lysine side chain (which affects water penetration
      differently for different protonation states) plays an important role in the pKa
      shifts.

PMID- 27700120
TI  - Substrates as Electron-Donor Precursors: Synthesis of Naphtho-Fused Oxindoles via
      Benzannulation of 2-Halobenzaldehydes and Indolin-2-ones.
AB  - An unusual benzannulation reaction has been realized by integrating
      intermolecular adol condensation with subsequent intramolercular base-promoted
      homolytic aromatic substitution. This novel cascade reaction provides a
      straightforward approach toward various naphtho-fused oxindoles from 2
      halobenzaldehydes and indolin-2-ones in the presence of Cs2CO3 in DMSO. The
      enolates of indolin-2-ones as new and internal electron donors have been
      demonstrated to initiate intramolecular radical dehalogenative coupling.

PMID- 27700121
TI  - Enantioselective Alkylative Kinetic Resolution of 2-Oxindole-Derived Enolates
      Promoted by Bifunctional Phase Transfer Catalysts.
AB  - The first strategy for bringing about highly enantioselective alkylative enolate
      kinetic resolutions using a simple phase-transfer protocol via SN2 chemistry has
      been developed. In the presence of a new squaramide-based quaternized cinchona
      alkaloid-derived catalyst and aqueous base, benzyl, allyl, and propargyl halides
      react with racemic substituted oxindoles to generate densely functionalized
      products with the two contiguous stereocenters, one of which is an all-carbon
      quaternary.

PMID- 27700119
TI  - Biomimetic ApoE-Reconstituted High Density Lipoprotein Nanocarrier for Blood
      Brain Barrier Penetration and Amyloid Beta-Targeting Drug Delivery.
AB  - Amyloid beta (Abeta) and its aggregation forms in the brain have been suggested
      as key targets for the therapy of Alzheimer's disease (AD). Therefore, the
      development of nanocarriers that possess both blood-brain barrier permeability
      and Abeta-targeting ability is of great importance for the intervention of AD.
      Here we constructed a biomimetic nanocarrier named apolipoprotein E (ApoE)
      reconstituted high density lipoprotein nanocarrier (ANC) from recombinant ApoE
      and synthetic lipids to achieve the above goals. alpha-Mangostin (alpha-M), a
      polyphenolic agent that can inhibit the formation of Abeta oligomers and fibrils
      and accelerate Abeta cellular degradation, was used as the model drug. Compared
      with the control liposome, ANC demonstrated about 54-fold higher cellular uptake
      in brain endothelial cell line in vitro in an ApoE-dependent manner and much
      higher brain delivery efficiency in vivo. Confocal microscopy analysis witnessed
      the penetration of ANC across the brain vessels and its accumulation at the
      surrounding of Abeta aggregates. Following the loading of alpha-M, the Abeta
      binding affinity of the nanoformulation (ANC-alpha-M) was not reduced but even
      enhanced. The effect of ANC-alpha-M on facilitating the microglia-mediated uptake
      and degradation of Abeta1-42 was enhanced by 336% and 29-fold when compared with
      that of the nontreated control and also much higher than that of ANC. Following
      intravenous administration for 2 to 4 weeks, ANC-alpha-M exhibited the most
      efficient efficacy in decreasing amyloid deposition, attenuating microgliosis,
      and rescuing memory defect in SAMP8 mice, an AD mouse model. Taken together, the
      findings of this work provided strong evidence that the ApoE-based biomimetic
      nanocarrier could provide a promising platform for brain drug delivery toward the
      treatment of AD.

PMID- 27700122
TI  - Pd-Catalyzed Tandem Cyclization via C-H Arylation and Acylation for the
      Construction of Polycyclic Scaffolds.
AB  - The first Pd-catalyzed tandem cyclization of imidazo[1,2-a]pyridines with 2
      chlorobenzaldehydes through C-H arylation and acylation is presented for the
      efficient synthesis of novel 6H-benzo[b]imidazo[5,1,2-de]quinolizin-6-ones. The
      direct acylation reaction proceeded smoothly without the aid of directing groups
      and in the presence of air as a clean and free terminal oxidant.

PMID- 27700123
TI  - Expedient Cobalt-Catalyzed C-H Alkynylation of (Enantiopure) Benzylamines.
AB  - A unified strategy for cobalt-catalyzed ortho-C-H bond alkynylation of
      benzylamines is reported. Simple, commercially available CoBr2 was used as a
      cobalt source. The developed alkynylation strategy is robust and efficient and
      has a broad substrate scope including 1 degrees , 2 degrees , and 3 degrees 
      benzylamines. The mechanistic study shows that C-H bond cleavage is reversible,
      and the kinetic study illustrates that the rate of reaction depends solely on the
      catalyst.

PMID- 27700125
TI  - Anticorrelation of Photoluminescence from Gold Nanoparticle Dimers with Hot-Spot
      Intensity.
AB  - Bulk gold shows photoluminescence (PL) with a negligible quantum yield of ~10-10,
      which can be increased by orders of magnitude in the case of gold nanoparticles.
      This bears huge potential to use noble metal nanoparticles as fluorescent and
      unbleachable stains in bioimaging or for optical data storage. Commonly, the
      enhancement of the PL yield is attributed to nanoparticle plasmons, specifically
      to the enhancements of scattering or absorption cross sections. Tuning the shape
      or geometry of gold nanostructures (e.g., via reducing the distance between two
      nanoparticles) allows for redshifting both the scattering and the PL spectra.
      However, while the scattering cross section increases with a plasmonic redshift,
      the PL yield decreases, indicating that the common simple picture of a
      plasmonically boosted gold luminescence needs more detailed consideration. In
      particular, precise experiments as well as numerical simulations are required.
      Hence, we systematically varied the distance between the tips of two gold
      bipyramids on the nanometer scale using AFM manipulation and recorded the PL and
      the scattering spectra for each separation. We find that the PL intensity
      decreases as the interparticle coupling increases. This anticorrelation is
      explained by a theoretical model where both the gold-intrinsic d-band hole
      recombination probabilities as well as the field strength inside the
      nanostructure are considered. The scattering cross section or the field strength
      in the hot-spot between the tips of the bipyramids are not relevant for the PL
      intensity. Besides, we not only observe PL supported by dipolar plasmon
      resonances, but also measure and simulate PL supported by higher order plasmonic
      modes.

PMID- 27700124
TI  - Tenofovir Containing Thiolated Chitosan Core/Shell Nanofibers: In Vitro and in
      Vivo Evaluations.
AB  - It is hypothesized that thiolated chitosan (TCS) core/shell nanofibers (NFs) can
      enhance the drug loading of tenofovir, a model low molecular weight and highly
      water-soluble drug molecule, and improve its mucoadhesivity and in vivo safety.
      To test this hypothesis, poly(ethylene oxide) (PEO) core with TCS and polylactic
      acid (PLA) shell NFs are fabricated by a coaxial electrospinning technique. The
      morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of
      the NFs are analyzed using scanning and transmission electron microscopies,
      liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines
      and Lactobacilli crispatus, fluorescence imaging and periodic acid colorimetric
      method, respectively. In vivo safety studies are performed in C57BL/6 mice
      followed by H&E and immunohistochemical (CD45) staining analysis of genital
      tract. The mean diameters of PEO, PEO/TCS, and PEO/TCS-PLA NFs are 118.56, 9.95,
      and 99.53 nm, respectively. The NFs exhibit smooth surface. The drug loading (13%
      25%, w/w) increased by 10-fold compared to a nanoparticle formulation due to the
      application of the electrospinning technique. The NFs are noncytotoxic at the
      concentration of 1 mg/mL. The PEO/TCS-PLA core/shell NFs mostly exhibit a release
      kinetic following Weibull model (r2 = 0.9914), indicating the drug release from a
      matrix system. The core/shell NFs are 40-60-fold more bioadhesive than the pure
      PEO based NFs. The NFs are nontoxic and noninflammatory in vivo after daily
      treatment for up to 7 days. Owing to their enhanced drug loading and preliminary
      safety profile, the TCS core/shell NFs are promising candidates for the topical
      delivery of HIV/AIDS microbicides such as tenofovir.

PMID- 27700126
TI  - Three-Year Clinical Evaluation of Class I Restorations in Posterior Teeth.
      Effects of Two Adhesive Systems.
AB  - This longitudinal study evaluated the clinical performance of 97 direct class I
      resin composite restorations after 3 years. The restorations were performed using
      2 types of adhesive systems: (1) AdperTM Single Bond Plus (SB) (3M ESPE,
      3mespe.com), which is a two-step etch-and-rinse system, and (2) Adper
      ScotchbondTM SE (SE) (3M ESPE), which is a two-step self-etching system. Two
      calibrated examiners evaluated the restorations using modified US Public Health
      Service criteria. The materials were applied following the manufacturer's
      instructions, and 15 patients received at least one of the two adhesive systems.
      The restorations were evaluated 7 days after placement (baseline) and again after
      3 years. Statistical analysis was performed using a proportion t-test at a
      significance level of 5% (P < .05). At baseline, all restorations received an
      Alpha score for the variable marginal discoloration and marginal integrity. After
      3 years, marginal discoloration received an Alpha score for 53.19% of the
      restorations performed with SB and 52.08% with SE. Marginal integrity was rated
      as Alpha for 65.96% and 68.75% of the restorations with SB and SE systems,
      respectively. The remaining restorations received Bravo scores for all variables.
      Eight restored teeth presented postoperative sensitivity at baseline (5 SB; 3
      SE), but no sensitivity was found after 3 years. No secondary caries was
      verified. No statistically significant differences were observed between the
      teeth restored with the SB and SE systems for marginal discoloration (P = .7880)
      and marginal integrity (P = .8132) after 3 years. Direct class I resin composite
      restorations performed with a two-step etch-and-rinse and a two-step self-etching
      adhesive system demonstrated satisfactory clinical performance after 3 years.

PMID- 27700127
TI  - Delayed Application Effect on Bond Strength of a Unidose Bonding Adhesive.
AB  - Adequate bonding between tooth structure and a composite is among the factors
      affecting long-term clinical success. Adhesives contain solvents, which are known
      to evaporate. The researchers sought to determine whether bond strength could be
      adversely affected when a package of a popular adhesive was left open during a
      patient visit.

PMID- 27700128
TI  - How to Bond Zirconia: The APC Concept.
AB  - Zirconia has become one of the most popular materials in dentistry. New high
      translucent zirconia ceramics have favorable optical properties and can be
      applied as monolithic full-contour restorations in various clinical indications
      for posterior and anterior teeth. However, having reliable cementation protocols
      is fundamental for clinical success of indirect ceramic dental restorations,
      including those made from zirconia materials. Resin bonding supports ceramic
      restorations and is necessary for onlays, laminate veneers, and resinbonded fixed
      dental prostheses. The APC zirconia-bonding concept is based on decades of
      research on how to achieve high and long-term durable bond strengths to high
      strength ceramics. It includes three practical steps: (A) airparticle abrasion,
      (P) zirconia primer, and (C) adhesive composite resin. This article discusses the
      history and development of high-translucent zirconia and explains the necessity
      for proper cementation. The rationale and science behind a simplified zirconia
      bonding concept is explained and illustrated with a clinical case presentation.

PMID- 27700129
TI  - Is Your Dental Adhesive Forgiving? How to Address Challenges.
AB  - The quality of the bond at the tooth-restoration interface is crucial to the
      clinical success of composite restorations. Not only is the adhesive crucial, but
      equally or even more important is the application. This article addresses
      pitfalls in the bonding technique, such as over-wetness/over-dryness, over
      etching, airthinning, and evaporation. Dental adhesives that are considered
      forgiving are less technique sensitive, thus potentially yielding more reliable
      bonding under various clinical conditions.

PMID- 27700130
TI  - Key Parameters of Hybrid Materials for CAD/CAM-Based Restorative Dentistry.
AB  - Hybrid materials are a recent addition to the dental armamentarium for computer
      assisted design/ computer-assisted manufacturing (CAD/CAM)-based restorative
      dentistry. They are intended to provide dentists with the capability of restoring
      single teeth in one appointment with a material that emulates the structure and
      physical properties of natural teeth. This article aims to provide an overview of
      currently available hybrid materials and offer the reader further understanding
      of their key clinical parameters and possible limitations.

PMID- 27700131
TI  - Adhesive Bonding to Hybrid Materials: An Overview of Materials and
      Recommendations.
AB  - Recently, hybrid materials have been introduced to the dental market. Together
      with computer-assisted design/computer-assisted manufacturing (CAD/CAM) composite
      resins, they form a new class of dental CAD/CAM materials that combine the
      positive effects of ceramics and composites. As bonding is essential for their
      clinical longevity, it is crucial to have a good understanding of their material
      properties and cementation protocols. This review offers clinicians an overview
      of available hybrid materials and recommendations for their respective adhesive
      placements.

PMID- 27700132
TI  - Placing Anterior Lithium-Disilicate Restorations Using a Dual-Cure Resin Cement.
AB  - Depending on the case, predictably seating today's esthetic indirect restorations
      can be challenging. Ultimately, the cementation and adhesive materials selected,
      combined with the techniques used for their placement, can greatly affect the
      quality and efficient delivery of laboratory-fabricated restorations. New
      adhesive bonding and cementation materials have the potential to simplify the
      delivery of indirect restorations and simultaneously reduce and/or eliminate many
      of the challenges clinicians face during the placement process. This article
      reviews the requisite characteristics of these materials and presents a case
      demonstrating their use when seating anterior lithium-disilicate restorations.

PMID- 27700133
TI  - Full-Contour Zirconia Fixed Partial Dentures as Chairside Applications: A Case
      Report.
AB  - Clinical application of zirconia has been expanding due to the high strength
      properties it offers. Initial use of zirconia was as a coping or substructure
      material replacing cast metal. More recent formulations have been introduced for
      monolithic zirconia contour designs. New chairside computer-aided design and
      computeraided manufacturing (CAD/CAM) technology has made it possible for
      dentists to deliver 3-unit bridges in a single appointment. This case report will
      present such a clinical application.

PMID- 27700134
TI  - Modern Indirect Restorations: The Right Material for Every Situation.

PMID- 27700135
TI  - Neonatal Androgen Exposure Causes Persistent Gut Microbiota Dysbiosis Related to
      Metabolic Disease in Adult Female Rats.
AB  - Alterations of gut microbiome have been proposed to play a role in metabolic
      disease, but the major determinants of microbiota composition remain ill defined.
      Nutritional and sex hormone challenges, especially during early development, have
      been shown to permanently alter adult female phenotype and contribute to
      metabolic disturbances. In this study, we implemented large-scale microbiome
      analyses to fecal samples from groups of female rats sequentially subjected to
      various obesogenic manipulations, including sex hormone perturbations by means of
      neonatal androgenization or adult ovariectomy (OVX), as a model of menopause, to
      establish whether these phenomena are related to changes in gut microbiota. Basic
      metabolic profiles concerning glucose/insulin homeostasis were also explored. The
      effects of the sex hormonal perturbations, either developmentally
      (androgenization) or in adulthood (OVX), clearly outshone the impact of
      nutritional interventions, especially concerning the gut microbiota profile.
      Notably, we observed a lower diversity in the androgenized group, with the
      highest Firmicutes to Bacteroidetes ratio, supporting the occurrence of durable
      alterations in gut microbiota composition, even in adulthood. Moreover, the
      elimination of adult ovarian secretions by OVX affected the richness of gut
      microbiota. Our data are the first to document the durable impact of sex steroid
      manipulations, and particularly early androgenization, on gut microbiota
      composition. Such dysbiosis is likely to contribute to the metabolic
      perturbations of conditions of obesity linked to gonadal dysfunction in the
      female.

PMID- 27700136
TI  - Adiponectin Deficiency Leads to Female Subfertility and Ovarian Dysfunctions in
      Mice.
AB  - Adipose tissue plays an important role in regulating female fertility, owing to
      not only its energy stores but also the endocrine actions of secreted adipokines.
      As one of the adipokines, adiponectin is almost exclusively secreted from the
      fat, and its circulating concentration is paradoxically reduced in obesity.
      Although recent studies implied a purported positive role of adiponectin in
      ovarian functions, definitive in vivo evidence has been sorely lacking. We have
      consistently observed subfertility in female adiponectin null mice and therefore
      postulated a protective role of adiponectin in ovarian functions. Female
      adiponectin null mice displayed impaired fertility, reduced retrieval of oocytes,
      disrupted estrous cycle, elevated number of atretic follicles, and impaired late
      folliculogenesis. Analysis of their sera revealed a significant decrease in
      estradiol and FSH but an increase in LH and testosterone at proestrus. In
      addition, we found marked reduction of progesterone levels at diestrus, a
      significant decrease in LH receptor expression as well as in the number of GnRH
      immunoreactive neurons. Adiponectin deficiency also altered the peak
      concentrations of LH surge and led to lower expression of Cytochrome P450 family
      11 subfamily A member 1 (P450scc), an enzyme critical for progesterone synthesis,
      as well as an increase in BCL2 associated X, apoptosis regulator and Insulin like
      growth factor binding protein 4 in atretic follicles. These physiological and
      molecular events were independent of insulin sensitivity. Thus, we have revealed
      a novel mechanism linking adiponectin and female fertility that entails
      regulation of reproductive hormone balance and ovarian follicle development.

PMID- 27700138
TI  - Published by Title Only.

PMID- 27700137
TI  - Carbon Monoxide and the Potential for Prebiotic Chemistry on Habitable Planets
      around Main Sequence M Stars.
AB  - Lifeless planets with CO2 atmospheres produce CO by CO2 photolysis. On planets
      around M dwarfs, CO is a long-lived atmospheric compound, as long as UV emission
      due to the star's chromospheric activity lasts, and the sink of CO and O2 in
      seawater is small compared to its atmospheric production. Atmospheres containing
      reduced compounds, like CO, may undergo further energetic and chemical processing
      to give rise to organic compounds of potential importance for the origin of life.
      We calculated the yield of organic compounds from CO2-rich atmospheres of planets
      orbiting M dwarf stars, which were previously simulated by Domagal-Goldman et al.
      (2014) and Harman et al. (2015), by cosmic rays and lightning using results of
      experiments by Miyakawa et al. (2002) and Schlesinger and Miller ( 1983a , 1983b
      ). Stellar protons from active stars may be important energy sources for abiotic
      synthesis and increase production rates of biological compounds by at least 2
      orders of magnitude compared to cosmic rays. Simple compounds such as HCN and
      H2CO are more readily synthesized than more complex ones, such as amino acids and
      uracil (considered here as an example), resulting in higher yields for the former
      and lower yields for the latter. Electric discharges are most efficient when a
      reducing atmosphere is present. Nonetheless, atmospheres with high quantities of
      CO2 are capable of producing higher amounts of prebiotic compounds, given that CO
      is constantly produced in the atmosphere. Our results further support planetary
      systems around M dwarf stars as candidates for supporting life or its origin. Key
      Words: Prebiotic chemistry-M dwarfs-Habitable planets-Cosmic rays-Lightning
      Stellar activity. Astrobiology 16, 744-754.

PMID- 27700139
TI  - Introduction to the Featured Reports: The MBL Awards for 2002.

PMID- 27700142
TI  - Neurobiologist James L. Olds Named 10th Editor of The Biological Bulletin.

PMID- 27700141
TI  - Plasma Gelsolin Level in HIV-1-Infected Patients: An Indicator of Disease
      Severity.
AB  - Plasma gelsolin (pGSN) is a multifunctional protein involved mainly in severing
      and clearing of actin filaments. Its level correlates with inflammation and
      several diseases making it a potential biomarker of diagnostic and prognostic
      values. The pGSN level in groups of treated and untreated HIV-1-infected Indian
      patients is investigated in this study. This study aims at investigating the
      levels of pGSN in HIV-1-infected patients across different age, sex, severity of
      disease, and treatment status. Blood samples of 213 patients were analyzed for
      CD4 counts by flow cytometry and pGSN was quantified by enzyme-linked
      immunosorbent assay (ELISA). The level of pGSN is significantly increased in HIV
      1 infected patients (227.2 +/- 54.3 MUg/ml) compared to healthy volunteers (167.9
      +/- 61.8 MUg/ml). The level correlates with CD4 cell counts as patients with
      lower CD4 counts showed higher pGSN levels and vice versa. Gender does not affect
      pGSN level; however, antiretroviral (ARV) treatment reduces pGSN toward normal.
      Within low CD4 cell count group, the untreated patients have 52% higher pGSN than
      healthy volunteers, whereas with treatment, the difference reduces to 24%.
      Similarly, high CD4 cell count (>350 cells/mm3) group of patients showed 44%
      increase in pGSN in untreated patients compared to 21% increase in treated
      patients. There is an upregulation of pGSN in HIV-1 infection and it is inversely
      correlated with CD4 cell counts. Treatment with ARV drugs decreases pGSN levels
      toward normal. The monitoring of pGSN level in HIV-1-infected patients could be
      an important indicator of severity of disease and recovery during treatment.

PMID- 27700140
TI  - Vitamin D Deficiency and Metabolism in HIV-Infected and HIV-Uninfected Men in the
      Multicenter AIDS Cohort Study.
AB  - We evaluated associations of serum 25-hydroxyvitamin D (25[OH]D) and 1,25
      dihydroxyvitamin D (1,25[OH]2D) levels in a cohort of HIV-infected and HIV
      uninfected men at risk for infection in the United States. Stored samples
      collected between 1999 and 2008 were tested for vitamin D metabolites between
      2014 and 2015. Vitamin D deficiency was defined as a serum concentration of
      25[OH]D <20 ng/ml. Multivariate models were used to assess associations of
      various demographic and clinical factors with vitamin D status. HIV-infected men
      on effective antiretroviral therapy (n = 640) and HIV-uninfected men (n = 99) had
      comparable levels of 25[OH]D and 1,25[OH]2D, and prevalences of vitamin D
      deficiency were 41% in HIV-infected and 44% in HIV-uninfected men, respectively.
      Self-reported black or other non-white race, obesity, and normal kidney function
      were significant predictors of vitamin D deficiency regardless of HIV serostatus.
      Lower CD4+ T cell count was associated with vitamin D deficiency in HIV-infected
      men, while current ritonavir use was protective. Self-reported black race was the
      only factor significantly associated with higher levels of 1,25[OH]2D (vs.
      whites; beta = 4.85 pg/ml, p = .003). Levels of 1,25[OH]2D and 25[OH]D were
      positively correlated in HIV-infected men (beta = 0.32 pg/ml, p < .001), but not
      in uninfected men (beta = -0.09 pg/ml, p = .623; p < .05 for interaction).
      Vitamin D deficiency was prevalent regardless of HIV serostatus in this cohort,
      suggesting that HIV infection did not confer additional risk of deficiency in
      this cohort of well-treated HIV-infected men. However, HIV infection and race may
      have implications for vitamin D metabolism and 1,25[OH]2D levels.

PMID- 27700143
TI  - William D. Cohen: Biologist, Educator, Editor (1938-2008).

PMID- 27700144
TI  - Clinician Perspectives on an Electronic Portal to Improve Communication with
      Patients and Families in the Intensive Care Unit.
AB  - RATIONALE: Communication in the intensive care unit (ICU) often falls short of
      patient and family needs, putting them at risk for significant physical and
      emotional harm. As electronic patient portals rapidly evolve, one designed
      specifically for the ICU might potentially enhance communication among patients,
      family members, and clinicians; however, the views of frontline ICU staff on such
      technology are unknown. OBJECTIVES: To identify clinician perspectives on the
      current state of communication among patients, families, and clinicians in the
      ICU, and assess their views on whether and how an electronic portal may address
      existing communication deficits and improve care. METHODS: Three focus groups
      comprised altogether of 26 clinicians from 6 ICUs, representing several
      disciplines in an academic medical center in Boston, Massachusetts. Transcripts
      were analyzed inductively for major themes using grounded theory. MEASUREMENTS
      AND MAIN RESULTS: We identified seven themes reflecting clinician perspectives on
      communication challenges and desired portal functionality: (1) comprehension and
      literacy; (2) results and updates; (3) patient and family preferences; (4)
      interclinician communication; (5) family informational needs; (6) the ICU as an
      unfamiliar environment; and (7) enhancing humanism through technology. Each theme
      included current gaps in practice, potential benefits and concerns related to an
      ICU communication portal, and participant recommendations. Benefits included
      enhanced education, patient/family engagement, and clinician workflow. Challenges
      included the stress and uncertainty of ICU care, fear of technology replacing
      human connection, existing interclinician communication failures, and the tension
      between informing families without overwhelming them. CONCLUSIONS: Overall,
      clinicians were cautiously supportive of an electronic portal to enhance
      communication in the ICU and made several specific recommendations for design and
      implementation. As new technologies expand opportunities for greater transparency
      and participation in care, clinician buy-in and positive impact will depend, in
      large part, on the extent to which the concerns of stakeholders are addressed. At
      the same time, clinicians anticipate several potential benefits that could help
      support provider workflow and engage patients and families through enhanced
      communication and humanism.

PMID- 27700146
TI  - Braveheart Constitutional change in ScotlandIf you thought the government was
      secretly making changes that would affect the way you work in the health service,
      would you be concerned? June Andrews discusses the radical legislative changes
      taking place in the NHS in Scotland this year.
AB  - The NHS is changing radically this year. It will affect the way nurses are paid,
      and the way they are held accountable. Education and training in the health
      service will differ across the UK, and laws may be passed that could mean people
      working in England pay more tax than those in Scotland. Why don't you know about
      it? If you live and work in Scotland, Wales, or Northern Ireland, you may well
      know. But this article is definitely for you if you live and work in England.

PMID- 27700145
TI  - Routine Antibiotic Prophylaxis Is Not Required for Patients Undergoing Shockwave
      Lithotripsy: Outcomes from a National Shockwave Lithotripsy Database in New
      Zealand.
AB  - PURPOSE: To assess the effectiveness of routine prophylactic antibiotics in the
      prevention of urinary tract infection (UTI) after extracorporeal shockwave
      lithotripsy (SWL) and identify predictors of UTI development in a multicenter
      series of over 10,000 stone cases treated in New Zealand over a 20-year period.
      MATERIALS AND METHODS: Patients treated with SWL on the Mobile Medical Technology
      vehicle between June 19, 1995 and December 1, 2014 were identified. Data
      collection was undertaken prospectively for patient, stone and treatment
      characteristics, and, retrospectively, for treatment outcomes. The primary
      outcome was clinical UTI, defined as development of UTI symptoms requiring
      antibiotic therapy. Secondary outcomes included urinary sepsis, need for hospital
      admission due to infectious complications, and length of hospital stay.
      Multivariate analysis was undertaken to identify factors independently associated
      with the development of post-SWL UTI. RESULTS: Antibiotic prophylaxis was used in
      62.1% (n = 6710) of cases. On comparing patients who received prophylactic
      antibiotics to those in whom antibiotics were withheld, no significant
      differences were observed in terms of post-SWL UTI (1.1% vs 1.3%, p = 0.335) or
      urinary sepsis (0.04% vs 0.15%, p = 0.075). The use of prophylactic antibiotics
      was not independently associated with post-SWL UTI (OR: 1.269, 95% CI: 0.886
      1.818, p = 0.194). Female gender, larger stone size, and higher number of
      delivered shocks were predictive of UTI development, but antibiotic prophylaxis
      did not appear to offer any benefit in this subgroup. CONCLUSIONS: Routine
      antibiotic prophylaxis was not associated with a reduction in clinical UTI after
      SWL in this cohort of over 10,000 stone cases in New Zealand.

PMID- 27700148
TI  - Frontliners.

PMID- 27700147
TI  - Refusing to be anyone's victim.
AB  - It's a terrible indictment on a so-called caring profession to admit it, but most
      nurses have been bullied at some time in their professional lives.

PMID- 27700149
TI  - Award for prehospital care.
AB  - Three nurses working in the field of prehospital emergency care are the first
      nurses to be awarded the Diploma in Immediate Medical Care from the Royal College
      of Surgeons of Edinburgh.

PMID- 27700150
TI  - Collect RTAs names and addresses only, says NHS.
AB  - NURSES are to be spared the embarrassment of collecting charges from road traffic
      accident victims.

PMID- 27700151
TI  - Nurses help search for avalanche mountaineers.
AB  - NURSES were in the front-line of the rescue and treatment of victims of the worst
      avalanche in the Scottish Highlands for 30 years.

PMID- 27700152
TI  - Grandmothers' role in attendances in A&E.
AB  - A small retrospective study from Philadelphia suggested that when grandmothers
      were involved in a child's care there was a greater use of A&E services. The
      researchers felt the reverse was true in Britain and that grandmothers had a
      beneficial role in supporting mothers and young children. They decided to
      investigate whether an involved grandmother affected use of services in the Royal
      Free Hospital A&E department.

PMID- 27700154
TI  - Pinpointing the problem of violence.
AB  - A recent rash of newspaper articles, a TV documentary and two consecutive hard
      hitting surveys have earned nursing the unenviable reputation of 'the most
      dangerous job in Britain'.While the profession has long recognised the gradual
      worsening of violent attacks in the workplace, the media furore in the press has
      left people demanding answers to some pertinent questions. Now the weight of
      public opinion is sitting heavy on the Government and, in turn, health service
      managers, as they are faced with two fundamental questions: Why is this
      happening? And What can be done to protect our nurses?

PMID- 27700153
TI  - Blood loss underestimated at scene of accidents.
AB  - Haemorrhage is a major cause of death in the trauma patient. In this study, the
      researchers aimed to investigate how accurate visual assessment of blood loss is
      at the scene of accident. Five case scenarios were set up using manikins and time
      expired whole human blood. The manikins were all dressed identically in jogging
      suit bottoms and a woollen jumper and were all laid supine on a concrete surface.
      Ten paramedics and ten emergency ambulance technicians were asked to estimate how
      much blood there was in each case.

PMID- 27700155
TI  - An open letter from Robert Sowney.
AB  - There can be no doubt that the devastating bomb in Omagh will be remembered as
      the most horrific in the history of Northern Ireland's recent troubles.

PMID- 27700156
TI  - Un title.
AB  - Nurses fought off competition from more than 160 colleagues to win two out of
      four research awards presented by health secretary Frank Dobson to staff at
      Salford Royal Hospitals NHS Trust last month. A&E nurses Olive Goodall and
      Gabrielle Lomas received a joint award for their research showing that trauma
      teams improved patient outcome, while Michael McEachern, charge nurse in elderly
      care, revealed that Do Not Resuscitate (DNR) orders are not being put into
      effect.

PMID- 27700158
TI  - Automobile airbags not without risk.
AB  - The wide use of automobile airbags has reduced the mortality and the incidence of
      serious injuries. However, automobile airbags appear to be associated with a
      variety of injuries including fatal injuries, ocular injuries, upper limb and
      chest injuries.

PMID- 27700159
TI  - A&E leading nurse wins special award.
AB  - Una Bell, Service Director, Whipps Cross A&E Department, London, has won a
      Lifetime Achievement Award at the Nurse 98 awards ceremony, held in London last
      month. Ms Bell who, along with her senior management roles in departments such as
      University College Hospital, King's College Hospital and Whipps Cross, is also
      involved with homelessness and drug misuse charities. In 1988, she was given
      Catholic of the Year award for her work following the King's Cross fire. She was
      also taken hostage in an armed siege last year in her department and was
      described by police as 'incredibly calm under such pressure'. Ms Bell's award,
      presented to her by Prime Minister Tony Blair, came as a complete surprise.
      Afterwards, she said she was 'thrilled and honoured'.

PMID- 27700157
TI  - Action against violence.
AB  - Patients who create mayhem at the Royal Hospitals NHS Trust, east London, are now
      handed a statement of how the trust expects them to behave and are asked to sign
      a contract agreeing that if they breach these standards they could be discharged
      and referred to another hospital. In addition, the patient's GP will be sent a
      letter asking for a referral elsewhere if the patient continues to make mischief.

PMID- 27700160
TI  - Witnessed resuscitation benefits relatives.
AB  - In a ground-breaking pilot study, researchers at Addenbrooke's Hospital,
      Cambridge have found relatives who witness the resuscitation of a loved one
      develop no adverse psychological effects. Established practice is for the
      relatives of critically ill patients to be excluded from the resuscitation area
      on the grounds that invasive procedures and aggressive resuscitation would
      distress the family and that their presence would compromise the performance of
      the clinical staff.

PMID- 27700161
TI  - Un title.

PMID- 27700162
TI  - A tribute to the Omagh nurses.
AB  - I admit that when I rang Robert Sowney, Clinical Nurse Specialist in South Tyrone
      Hospital A&E department and a member of the RCN A&E Nursing Association Steering
      Group, I did so with some trepidation. How do you convey support in the aftermath
      of the Omagh bombing without feeling intrusive? Where is the boundary between
      empathy and voyeurism? We spoke long into the evening about Saturday, 15 August
      and the days that followed.

PMID- 27700163
TI  - Harsh reality of emergency careThe Omagh coverage showed hospital staff whose
      lives were intertwined with the community they serve.
AB  - Television is not always a good medium for nurses and doctors. Needing to find a
      visual picture to demonstrate a complex set of skills, knowledge and actions, it
      tends to use the extreme or the obvious image - doctors are either surgeons or
      GPs, nurses are in uniform, and the health service as a whole is represented by
      hospital buildings.

PMID- 27700164
TI  - St Augustine's a South African trauma unit.
AB  - As a hospital resuscitation officer, I have a keen interest in all types of
      resuscitation to include trauma and prehospital care. My background is critical
      care nursing and I have undertaken the majority of advanced life support based
      courses, but like most of my colleagues our exposure to major trauma, especially
      penetrating trauma, is variable. Frimley Park Hospital is a 700 bedded district
      general hospital and our A&E department sees over 70,000 patients per year. On
      average, I will attend five clinical emergencies per week with the majority being
      medical. This mix of emergencies is common to all UK hospitals and even in large
      hospitals, such as The North Staffordshire Infirmary only 0.2 per cent of the
      work load is life-threatening injury ( Redmond 1997 ). The majority of UK trauma
      is blunt in origin and, although we tend to operate a system of trauma teams,
      there are still deficiencies in our care of trauma patients. I believe that part
      of the problem is lack of exposure.

PMID- 27700167
TI  - Use of liaison psychiatrists in A&E.
AB  - In this paper, a consultant psychiatrist argues that apart from self-referrals,
      there seems to be a trend among GPs, police surgeons, police officers and even
      solicitors to refer to the A&E for emergency psychiatric assistance. While there
      is a view that such 'inappropriate' use should be discouraged, an alternative
      policy would be to recognise the accessibility of A&E and ensure facilities and
      staffing are adequate to provide a psychiatric emergencies service equal to that
      provided for medical emergencies.

PMID- 27700165
TI  - Ventilator poses no fire risk to patient.
AB  - In this study, oxygen concentrations were measured at 12 points around a
      caridiopulmonary resuscitation practice mannequin following simulated
      ventilations with a self-inflating bag, a 'Waters' bag and a ventilator to
      determine whether increased oxygen concentrations may contribute to the risk of
      combustion from arcing defibrillator paddles.

PMID- 27700168
TI  - Oscillating saw injuries.
AB  - The aim of this study was to assess the incidence of injuries to patients who
      have had a plaster cast removed by oscillating circular saw. The record of each
      patient who had his or her plaster removed was kept in the plaster room and later
      studied.

PMID- 27700169
TI  - Nurses rush to help in omagh bomb atrocity.
AB  - N urses flocked from both sides of the border to help treat casualties from
      Saturday's bombing in Omagh, Co Tyrone.

PMID- 27700170
TI  - ?
AB  - The Royal Free Hospital A&E department have won this year's Henrietta Cup
      Rounders competition, overcoming stiff opposition from the Royal London Hospital
      A&E. Team captains from left to right: Howard Jones (Royal Free); and Toni Lynch
      (Royal London).

PMID- 27700171
TI  - A&E nurse leader earns doctorate in the normal troubles of work.
AB  - Lynn Sbaih, a respected A&E nurse and author, has recently been awarded a PhD
      from the University of Manchester.

PMID- 27700172
TI  - Glasgow A&E on the Net.
AB  - A new internet site has been opened by Glasgow Royal Infirmary A&E staff.
      Browsers who visit the site can view pictures of individual areas within the
      department as well as discovering staff clinical and research interests.

PMID- 27700173
TI  - A&E nurse treks across Jordan in aid of cot death research.
AB  - Mary Osborne , an A&E staff nurse at Leighton Hospital, Cheshire, is preparing to
      undertake an arduous five day 100km trek across Jordan in aid of cot death
      research and support. The trek takes place in March 1999, and Ms Osborne has
      already started both training and finding the L2,000 sponsorship she needs for
      the Foundation for the Study of Infant Deaths (FSID).

PMID- 27700174
TI  - The MBL Awards for 2003.

PMID- 27700175
TI  - Published by Title Only.

PMID- 27700176
TI  - Published by Title Only.

PMID- 27700177
TI  - No trolley waits at all.
AB  - I was working in an A&E department on the day of Caswatch, the annual snapshot
      survey of trolley waits undertaken by the Association of Community Health
      Councils in England and Wales (ACHCEW). Early in the afternoon, a sister came
      over to a few of us and lividly described a conversation she had just had with
      the Director of Nursing and Quality. She was informed that there would be no
      trolley waits that day in A&E because 'we have made sure beds will be available
      on the wards'.

PMID- 27700178
TI  - Uncut Esophagojejunostomy with Double Jejunal Pouch: An Alternative
      Reconstruction Method that Improves the Quality of Life of Patients after Total
      Gastrectomy.
AB  - BACKGROUND: Currently, there is no optimal digestive tract reconstruction
      technique well recognized by scholars after total gastrectomy. In this study, a
      new reconstruction method, which is modified from the classic Roux-en-Y
      procedure, an uncut jejunal esophageal anastomosis with double jejunal pouch
      (UJEA-DJP) was established, and its advantages for improving the quality of life
      of patients who undergo total gastrectomy were analyzed. METHODS: Altogether 160
      patients with gastric cancer enrolled in our center from September 2009 to March
      2012 received radical D2 total gastrectomy. According to the reconstruction
      methods used, these patients were divided into three groups: UJEA-DJP (n = 63),
      Roux-en-Y (n = 45), and P-loop with Roux-en-Y esophagojejunostomy (P-RY; n = 52).
      The operation time for reconstruction, complications, prognostic nutritional
      index (PNI), and the Visick classification among the three groups were analyzed.
      RESULTS: We found that UJEA-DJP has advantages over Roux-en-Y and P-RY regarding
      the time of digestive tract reconstruction, incidence rates for long-term
      complications, postoperative nutritional index, body weight recovery, and the
      Visick classification for subjective feelings (p < .05). CONCLUSIONS: The UJEA
      DJP surgical procedure has the advantages of intestinal continuity and double
      pouch construction, which can significantly reduce long-term complications and
      improve the long-term quality of life of patients after surgical procedure.

PMID- 27700182
TI  - Joint conference.
AB  - The Irish Emergency Nurses Association and RCN A&E Nursing Association are
      holding a conference in Newry, Co Down on November 25. Topics include an update
      on the Faculty of Emergency Nursing, the management of chest trauma, obstetric
      emergencies, management of pre-tibial lacerations, and what's hip on the drug
      scene. Cost: L50 RCN members; L70 for nonmembers (includes dinner and disco).
      Conference only L35. Contact, Claire Morrissy, RCN, 17 Windsor Avenue, Belfast.
      Tel 01232-668236.

PMID- 27700180
TI  - Acute biliary pancreatitis: focus on recurrence rate and costs when current
      guidelines are not complied.
AB  - BACKGROUND: International guidelines recommend cholecystectomy within 2-4 weeks
      after mild to moderate acute biliary pancreatitis (ABP) to prevent recurrence. We
      aimed to investigate the compliance to guidelines concerning early
      cholecystectomy and the associated costs. METHODS: Admissions for ABP 2011-2013
      were retrospectively reviewed. Classification was made according to the revised
      Atlanta classification. Treatment, time to surgery and recurrence, as well as
      cost analysis for both in-hospital costs and loss of production (LOP) were
      performed. RESULTS: In total, 254 patients were included. Some 202 of the ABP
      patients (80%) underwent definitive treatment during their first attack of ABP
      (68% cholecystectomy, 17% endoscopic retrograde cholangiopancreatography (ERCP),
      15% both interventions) and 186 (73%) were treated within 1 month of discharge.
      Patients with ERCP alone were significantly older than cholecystectomy cases (p <
      .001), but no significant difference was observed between those who underwent
      ERCP or no treatment (p = .071). Mild ABP had intervention earlier (p < .001). In
      all, 52 patients (20%) had no intervention, out of which 15 were readmitted due
      to pancreatitis, compared to 3 patients of those treated at the initial admission
      (p < .001). The mean cost for hospital care and LOP in mild ABP was ?6882 +/-
      3010 and ?9580 +/- 7047 for moderate ABP (p = .001). The cost for a recurrent
      episode was ?16,412 +/- 22,367. CONCLUSION: By improved compliance to current
      guidelines concerning the management of ABP, recurrence rate and associated costs
      can potentially be reduced.

PMID- 27700183
TI  - Older people in A&E a position statement.
AB  - Old age is not a disease, but is the natural, inevitable progression of an
      individual along life's continuum. The older generation is the fastest growing
      population, particularly among those over 85 years, and is a major consumer of
      healthcare, in comparison with those who are younger ( Butler 1997 , Ham 1993 ).
      These health and social needs are numerous and complex.

PMID- 27700181
TI  - Laparoscopic-Assisted Percutaneous Endoscopic Gastrostomy Combined with CT-GC.
AB  - PURPOSE: Despite the widespread use of percutaneous endoscopic gastrostomy (PEG)
      tubes, their placement may be associated with a variety of complications,
      including gastrocolic fistula. MATERIALS AND METHODS: In total, seven high-risk
      individuals diagnosed using computed tomography (CT)-gastrocolonography (GC)
      underwent laparoscopic-assisted PEG (LAPEG) placement. Study endpoints included
      the success of LAPEG under local anesthetic and intravenous sedation, inability
      to thread the PEG tube, the eventual tube location, the number of tube
      adjustments needed, adverse events, the operating time, and PEG tube-related
      infection. RESULTS: In total, 135 PEG procedures were performed during this
      study. Successful CT-GC was achieved in all 135 patients, and we successfully
      used a standard PEG technique to place the gastrostomy tube in 128 patients
      (95%). In seven patients (5%), the LAPEG technique was used because the
      transverse colon became interposed between the abdominal wall and the anterior
      wall of the stomach. LAPEG procedure-related minor complications were observed in
      two patients. CONCLUSIONS: LAPEG combined with CT-GC can be used for patients
      with difficult anatomical orientations and may minimize the risk of complications
      in PEG placement.

PMID- 27700184
TI  - Frontliners.

PMID- 27700185
TI  - Staff demand protection after violent attack in A&E.
AB  - Nurses at a London hospital are protesting against lax levels of security in A&E
      in the wake of a recent attack on three nurses and a healthcare assistant.

PMID- 27700179
TI  - Epigenetic control of the tumor microenvironment.
AB  - Stromal cells of the tumor microenvironment have been shown to play important
      roles in both supporting and limiting cancer growth. The altered phenotype of
      tumor-associated stromal cells (fibroblasts, immune cells, endothelial cells
      etc.) is proposed to be mainly due to epigenetic dysregulation of gene
      expression; however, only limited studies have probed the roles of epigenetic
      mechanisms in the regulation of stromal cell function. We review recent studies
      demonstrating how specific epigenetic mechanisms (DNA methylation and histone
      post-translational modification-based gene expression regulation, and miRNA
      mediated translational regulation) drive aspects of stromal cell phenotype, and
      discuss the implications of these findings for treatment of malignancies. We also
      summarize the effects of epigenetic mechanism-targeted drugs on stromal cells and
      discuss the consideration of the microenvironment response in attempts to use
      these drugs for cancer treatment.

PMID- 27700186
TI  - Ageism in care.
AB  - I'm often struck, but no longer surprised, at the number of older people whose
      lives were defined by the events of 60 years ago during the Second World War. So
      often, following an unsuccessful resuscitation, a grieving wife would comment
      that her husband had fought in the war. Like many of that generation, including
      my own father, they speak about what happened matter of factly rather than
      vainly, yet quite literally without their sacrifices we almost certainly would
      not have the freedoms we take for granted.

PMID- 27700187
TI  - An Update on Naltrexone/Bupropion Extended-Release in the Treatment of Obesity.
AB  - INTRODUCTION: As the prevalence of obesity continues to increase, the need for
      effective long-term treatment strategies for the overweight and the obese is
      critical. Pharmacology fills a large treatment gap between behavioral therapy,
      which is insufficient for the majority of patients, and devices and surgery,
      which are available to only a subset of patients. Naltrexone HCl and bupropion
      HCl Extended-Release (naltrexone XR/bupropion XR) was approved by the Food and
      Drug Administration for chronic weight management in 2014. Areas covered: This
      review illustrates the efficacy and safety of naltrexone XR/bupropion XR by
      examining data from clinical trials. It also provides an overview of the market
      and presents the pharmacodynamics and pharmacokinetics of naltrexone and
      bupropion. Expert opinion: The efficacy and safety profile of naltrexone
      XR/bupropion XR makes it a viable option for many patients who could benefit from
      its distinctive mechanism. The medication was shown to produce additive weight
      loss when combined with an intensive behavioral modification program and it may
      improve food cravings and eating behaviors. Compared to the other three
      antiobesity medications approved since 2012, naltrexone XR/bupropion XR is
      neither a controlled substance nor an injectable agent.

PMID- 27700188
TI  - New fixed dose chemical combinations: the way forward for better diabetes type II
      management?
AB  - INTRODUCTION: Diabetes type II is a complex disease with unclear pathophysiology.
      Lack of adherence and high cost of medicines invariably make the management of
      diabetes type II highly challenging. Newer fixed drug combinations (FDC) are cost
      effective and can improve the medication adherence thereby prevent the
      complications of diabetes. Safety and efficacy of newer FDCs are not well
      established in all populations. Moreover, extrapolating the efficacy and safety
      data globally may not be pragmatic. Our review will discuss newer chemical
      combinations available for the treatment of diabetes type II. Areas covered: In
      the present review, the authors discussed the newer FDCs available as add on
      therapy to the existing pharmacological interventions of diabetes type II that
      have shown promising results in various randomised trials with regard to efficacy
      and safety. Expert opinion: Safety and efficacy data of newer FDCs available as
      an adjuvant therapy to conventional pharmacological interventions in diabetes
      type II revealed that fewer new FDCs are promising with their high efficacy and
      low adverse effect. However, there is a need to explore the place in therapy to
      establish the utility of FDC in diabetes type II management.

PMID- 27700189
TI  - Differentiation of obese patients at moderate or higher Findrisc score based on
      their atherogenic index.
AB  - OBJECTIVES: The purpose of this study was to reveal different subgroups of
      patients with at least moderate risk of developing diabetes in the next 10 years,
      based on clustering of cardiovascular risk factors. METHODS: We performed a one
      center cross-sectional study of adult patients (n = 109, median age 45 years)
      with Findrisc score of above 11 out of 26 maximum. We included in the cluster
      analysis anthropometrics, lipid and carbohydrate parameters obtained in oral
      glucose tolerance test (OGTT), insulin, C-peptide, creatinine, C-reactive
      protein, liver enzymes, beta-cell function, insulin sensitivity and insulin
      resistance (HOMA calculations). We also evaluated the atherogenic index of plasma
      (AIP). RESULTS: We identified three metabolic phenotypes of patients with at
      least moderate Findrisc score-one 'male' (cluster AM, n = 24), and two 'female'
      phenotypes (cluster AW, n = 9 and cluster BW, n = 76). Men were almost homogenous
      for their metabolic phenotype, with lower fat percentage than women (p < .05).
      Most of the women (cluster BW, n = 76) presented with better metabolic pattern
      i.e. lower insulin resistance, lower C-reactive protein, lower degree of obesity
      and visceral fat rating (p < .05), despite the higher fat percentage (p < .05).
      Some of the women, however, (cluster AW, n = 9) presented with parameters very
      similar to that of men (cluster AM) and significantly higher than in cluster BW.
      Despite the lack of significant differences in lipid parameters among clusters,
      AIP was significantly lower in cluster BW (p < .05). CONCLUSION: Most of the
      women presented with clearly less unfavorable atherogenic risk than men. Two
      different phenotypes of obese women with at least moderate Findrisc score were
      revealed, and the level of inflammation seems to be the main discriminant factor.
      Larger prospective studies are required to elucidate whether those are really two
      different pathogenically phenotypes or if they belong to the same phenotype's
      continuum.

PMID- 27700190
TI  - Phenolics from Lagotis brevituba Maxim.
AB  - A phytochemical investigation on Lagotis brevituba led to the isolation and
      characterisation of 11 phenolic compounds: p-hydroxy-benzoic acid 1, methyl 3,4
      dihydroxybenzoate 2, vanillic acid 3, protocatechuic acid 4, caffeic acid 5,
      glucose ester of (E)-ferulic acid 6, p-coumaric acid 7, vanillin 8, diosmetin-7-O
      beta-d-glucoside 9, chrysoeriol 10 and luteolin 11. Their structures were
      elucidated using spectroscopic methods and by comparison with data in the
      literature. Compounds 1-6 were first obtained from the genus Lagotis, and
      compounds 1-9 were isolated from L. brevituba for the first time. Compound 4 and
      11 displayed remarkable antioxidant activities against DPPH radical (IC50 = 5.60
      +/- 0.09, 27.5 +/- 0.06 mg/L, respectively), which were superior to positive
      control rutin. And compound 11 was also superior to rutin in ABTS assay (IC50 =
      2.04 +/- 0.13 mg/L).

PMID- 27700191
TI  - Outcomes of Parathyroid Autotransplantation During Total Thyroidectomy: A
      Comparison with Age- and Sex-Matched Controls.
AB  - PURPOSE: To determine the effect of parathyroid autotransplantation (PA) on
      postoperative hypocalcemia in cases of total thyroidectomy. MATERIALS AND
      METHODS: Cases undergoing total thyroidectomy and PA were compared with age and
      sex-matched controls who had not undergone PA. The postoperative percentage
      changes (PC) of parathyroid hormone (PTH) and calcium (Ca+2) in the first 12-24
      hours (12-24hr->preop), between the 1st-3rd weeks (1-3wk->preop) and at the 6th
      month (6mo->preop), the rates of hypocalcemia (Ca+2< 8mg/dL) and low PTH level
      (PTH< 15 pg/mL), permanent hypocalcemia, inadvertent parathyroidectomy in both
      groups were compared. RESULTS: The number of patients with PTH12-24hr<15 pg/mL
      was significantly higher (n:34,(55.7%)) than the number of patients in the
      control group (n:16(26.2%)), (p=0.001). The rate of decrease in the blood Ca+2
      median PC (6mo->preop) was significantly higher in the PA group (4.2%) than the
      control group (1.1%), (p=0.008). There was no significant difference between the
      2 groups in terms of the postoperative frequency of hypocalcemia (p>0.05). In the
      PA&age<=50 group, the rate of inadvertent parathyroidectomy was higher than that
      of cases over age 50 (p=0.029). CONCLUSION: In spite of the presence of an
      increased postoperative hypocalcemia trend in cases requiring PA during total
      thyroidectomy, the rates of transient and permanent hypocalcemia were not
      different to the control cases. But the frequency of cases with low PTH level in
      cases undergoing PA was higher than that of the control cases. In cases of 50
      years of age and under, who had undergone PA, the possibility of inadvertent
      parathyroidectomy increased.

PMID- 27700192
TI  - Studded and unstudded winter tires in fatal road accidents in Finland.
AB  - OBJECTIVE: The aim of the study was to compare the safety effects of studded and
      unstudded winter tires based on fatal road accidents. METHODS: The data included
      958 road accidents involving a passenger car or van that occurred in Finland from
      November to March between 1997 and 2012. RESULTS: Comparing the proportions of
      winter tire type in accidents and in general traffic showed that the overall
      effect of tire type on the number of accidents was not significant, although
      studded tires reduced fatal accidents by 10-15%. Compared to unstudded tires,
      studded tires reduced accidents significantly only on bald ice in 2005-2012.
      Drivers using unstudded tires were more experienced and their profession was more
      frequently related to driving. In addition, the vehicle age was lower for
      vehicles with unstudded tires. On the other hand, the state of repair was less
      pertinent for unstudded than for studded tires. These confounding factors offset
      their effects to some degree. CONCLUSIONS: The risk of fatal road accidents in
      winter between studded and unstudded tires does not differ significantly.
      However, the accident risk has recently been substantially higher on bald ice for
      unstudded than for studded tires. The magnitude of this risk difference is
      difficult to determine without specific information on exposure by road surface.

PMID- 27700193
TI  - Approaches for targeting cancer stem cells drug resistance.
AB  - INTRODUCTION: Several reports have suggested that a population of
      undifferentiated cells known as cancer stem cells (CSCs), is responsible for
      cancer formation and maintenance. In the last decade, the presence of CSCs in
      solid cancers have been reported. Areas covered: This review summarizes the main
      approaches for targeting CSCs drug resistance. It is indeed known that CSCs may
      contribute to resistance to conventional chemotherapy, radiotherapy and targeted
      agents. Among the mechanisms by which CSCs escape anticancer therapies, removal
      of therapeutic agents by drug efflux pumps, enhanced DNA damage repair,
      activation of mitogenic/anti-apoptotic pathways; the main features of CSCs,
      stemness and EMT, are involved, as well as the capability to evade immune
      response. Expert opinion: Different approaches are suitable to target CSCs
      mediated drug resistance. Some of them are currently under clinical evaluation in
      different cancer types. A better understanding of CSC biology, as well as more
      accurate study design, may maximize the therapeutic effects of these agents. In
      this respect, it is important to establish: (i) which molecules should be
      targeted; (ii) what drug combinations may be suitable; (iii) which patient
      settings will CSC targeting offer the highest clinical benefit; and (iv) how to
      integrate therapeutic approaches targeting CSCs with standard cancer therapy.

PMID- 27700194
TI  - Neurological abnormalities in localized scleroderma of the face and head: a case
      series study for evaluation of imaging findings and clinical course.
AB  - INTRODUCTION: Localized scleroderma (LoS) of the face and head is often
      associated with neurological manifestations and/or imaging abnormalities in the
      central nervous system (CNS). CASE SERIES: We present an analysis of 20 cases of
      LoS affecting the face and head. The CNS symptoms and/or abnormalities in high
      resolution computed tomography (HRCT) and/or magnetic resonance imaging (MRI)
      were observed in 12 patients (60%). In addition to the mild and unspecific
      disorders (e.g. headaches), serious neurological complications probably in the
      course of vasculitis were revealed: epilepsy (in two patients), epilepsy and
      pyramidal sings (in one patient). Neurological disorders and LoS occurred at the
      same time (in three patients) or at the course of the disease (nine patients) and
      no later than 29 years since the onset of the disease. No link between
      neurological disorders and the LoS clinical morphology, immunological and other
      laboratory parameters has been established. CONCLUSIONS: CNS involvement is not
      correlated with the clinical course of the facial and head LoS and may occur
      years after the disease initial symptomatology. Imaging follow-up is not required
      if there is not any emerging neurological symptom. In some cases, however, both
      HRCT and MRI are useful for monitoring disease evolution and addressing
      therapeutic choices.

PMID- 27700195
TI  - First-Night Effect on Sleep in Different Female Reproductive States.
AB  - OBJECTIVES: In sleep laboratory studies, the new environment is generally
      considered to disturb sleep during the first night. However, older women have
      rarely been studied. Although menopause and hormone therapy affect sleep, their
      impact on the first-night effect is virtually unknown. PARTICIPANTS: Four groups
      of women with no sleep laboratory experience: young on hormonal contraceptives (n
      = 11, 23.1 [0.5] years), perimenopausal (n = 15, 48.0 [0.4] years),
      postmenopausal without hormone therapy (HT; off-HT, n = 22, 63.4 [0.8] years) and
      postmenopausal with HT (n = 16, 63.1 [0.9] years). PROCEDURE: A cross-sectional
      study. METHODS: Polysomnography was performed over two consecutive nights and the
      first-night effect and group differences were evaluated. Questionnaire-based
      insomnia and sleepiness scores were correlated to sleep variables and their
      between-night changes. RESULTS: Although sleep in young women was deeper and less
      fragmented than in the other groups, first-night effect was similar in all study
      groups. Total sleep time, sleep efficiency, and S1 and S2 sleep increased, and
      wake after sleep onset, awakenings per hour of sleep, S2 and REM latencies, and
      percentage of SWS decreased from the first to the second night. Perimenopausal
      women had more insomnia complaints than other women. Insomnia complaints were
      associated with more disturbed sleep but not with the first-night effect.
      CONCLUSIONS: A first night in a sleep laboratory elicits a marked interference of
      sleep architecture in women of all ages, with a carryover effect of lighter sleep
      on the second study night. Menopausal state, HT use, or insomnia complaints do
      not modify this effect.

PMID- 27700197
TI  - Association appoints new RCN A&E Chair.
AB  - Lynda Holt, A&E Clinical Manager at Warwick Hospital has become Chair of the RCN
      A&E Nursing Association following the resignation of Karen Castille who has been
      seconded to the Department of Health (England) to work on the A&E modernisation
      programme.

PMID- 27700198
TI  - New appointments at DoH (England).
AB  - A series of new personnel have joined the Department of Health (England) with
      responsibility for A&E and emergency services.

PMID- 27700196
TI  - Pediatric Blunt Neck Trauma Causing Esophageal and Complete Tracheal Transection.
AB  - BACKGROUND: Blunt injuries to the cervical trachea remain rare but present unique
      and challenging clinical scenarios for prehospital providers. These injuries
      depend on prehospital providers either definitively securing the injured airway
      or bridging the patient to a treatment facility that can mobilize the necessary
      resources. CASE SUMMARY: The case presented here involves a clothesline injury to
      a pediatric patient that resulted in complete tracheal transection and partial
      esophageal transection. Ground and air prehospital providers utilized a stepwise
      approach to this airway injury and achieved a favorable outcome. The patient was
      serendipitously intubated through a blind nasal approach that entered the
      proximal esophagus, exited through the tear and entered the distal trachea.
      DISCUSSION: There is a paucity of literature describing the successful management
      of these devastating injuries. While some authors have advocated for early
      flexible fiberoptic intubation or proceeding directly to tracheostomy, these
      techniques are not available in the prehospital environment. This case also
      highlights the inherent issues with proceeding to cricothyroidotomy in patients
      with tracheal trauma and should give all providers pause before considering this
      management technique. CONCLUSION: Ultimately, a systematic approach to all
      airways will ensure that prehospital providers are best prepared for even the
      most challenging scenarios.

PMID- 27700199
TI  - Help wanted.
AB  - Anthony McGrath , Senior Lecturer at Middle-sex University, is undertaking a
      doctorate to examine 'To what extent does masters degree education affect
      clinical prac-tice'. He would like to hear from anyone who has undertaken such a
      degree programme and remains in clinical practice to discuss their perceptions of
      the value of the educational and clinical benefits of their masters degree
      education.

PMID- 27700200
TI  - Frontliners.

PMID- 27700201
TI  - Un title.

PMID- 27700202
TI  - A&E nurses plan to sue over post-traumatic stress.
AB  - Nurses are planning to take their employers to the High Court, claiming that NHS
      trusts failed to protect them from post-traumatic stress disorder (PTSD).

PMID- 27700203
TI  - Call for agreement in millennium pay.
AB  - Furious NHS managers have joined nursing unions and professional bodies in
      condemning millennium holiday pay arrangements for health service staff. A survey
      by research organisation Industrial Relations Services found that 90 per cent of
      a sample of 85 employers want a national agreement instead of having to negotiate
      local deals. In its report, IRS says the absence of a national agreement has led
      to unacceptably wide variations in pay rates.

PMID- 27700204
TI  - Vomiting after head injury.
AB  - Researchers in this study sought to determine whether the presence and severity
      of post-traumatic vomiting can predict the risk of a skull vault fracture in
      adults and children. Data were analysed relating to a consecutive series of 5416
      patients including children who presented to an emergency service in the UK
      during a one-year study period with a principal diagnosis of head injury.

PMID- 27700206
TI  - Closed circuit TV does not reduce violence.
AB  - Closed circuit television in city centres has no obvious influence on the level
      of assaults recorded in inner city hospitals' A&E departments in Wales, according
      to research based on studies of three large hospital units. The research also
      showed that A&Es were better barometers of levels of violence in the community
      than police records.

PMID- 27700205
TI  - From Star Wars to 'turf wars'.
AB  - Just as we are witnessing the re-emergence of Star Wars, it seems the 'turf wars'
      that have dogged A&E care are back. Since its inception as a specialty, A&E
      nurses have been accused of being 'Jacks (and Jill's, to be politically correct)
      of all trades and masters of none'. The inference being that all we do is 'mind'
      patients until they receive definitive care. Clearly this is not the case. As A&E
      nurses have demonstrated over the years, our skills are in the recognition and
      management of acute illness or injury, regardless of the patient's age, physical
      or psychological condition. Rather than being a 'master of none' we are masters
      of immediate care.

PMID- 27700207
TI  - Putting the nurse back into triageCherine Woolwich looks at the current trends in
      nurse triage and finds she has been asking similar questions to the ones posed by
      Edwards ( 1999 ) in 'What's wrong with triage?' which appeared in last month's
      issue of Emergency Nurse.
AB  - I was one of those A&E nurses in the mid-eighties and early nineties who was
      committed to the concept of nurse triage as a means of providing better care for
      patients. I felt it was crucial for emergency nurses to recognise the importance
      of nurse triage and the part that they could play in its development. Estrada (
      1981 ) referred to 'non-professional triage' when patients were not seen and
      assessed by a nurse. She said of nurse triage that it was 'a professional
      judgment, made by a professional nurse'.

PMID- 27700208
TI  - First trimester serum levels of the soluble transcobalamin receptor, holo
      transcobalamin, and total transcobalamin in relation to preeclampsia risk.
AB  - BACKGROUND: Human placenta expresses CD320, a receptor that ensures the uptake of
      holo-transcobalamin (holoTC). Soluble CD320 (sCD320) is present in the
      circulation and its concentration increases during pregnancy. AIMS: To
      investigate a possible association of sCD320, holoTC and total transcobalamin
      (TC) with the risk of subsequent preeclampsia using serum samples from
      asymptomatic first trimester pregnant women. Moreover, we aimed to establish
      reference intervals of the aforementioned biomarkers for first trimester pregnant
      women who remained healthy throughout pregnancy. STUDY DESIGN: This study was a
      retrospective case-control study that we performed on biobank serum samples.
      Cases (n = 50) and controls (n = 198) (matched for gestational age and date of
      sample collection) were asymptomatic women in early pregnancy [median (range)
      gestational age = 10 (8-12) weeks]. Cases developed preeclampsia while the
      controls remained normotensive throughout pregnancy. We measured the serum
      concentration of sCD320, holoTC, and total TC by using in-house ELISA methods.
      RESULTS: First trimester median concentrations of sCD320, holoTC and total TC
      were not significantly different between cases and controls. The odd ratio for
      developing preeclampsia based on exposure to low or high levels of sCD320, holoTC
      or total TC at first trimester was not significant. The reference intervals (2.5
      97.5% percentiles (median)) derived from the controls were 50-170 (90) pmol?L for
      sCD320, 20-140 (70) pmol?L for holoTC and 560-1300 (810) pmol?L for total TC.
      CONCLUSIONS: The risk of preeclampsia is not predicted by first trimester serum
      concentrations of sCD320, holoTC or total TC. The first trimester reference
      intervals for the three parameters is reported.

PMID- 27700209
TI  - Development of a Child Abuse Checklist to Evaluate Prehospital Provider
      Performance.
AB  - OBJECTIVES: To develop and provide validity evidence for a performance checklist
      to evaluate the child abuse screening behaviors of prehospital providers.
      METHODS: Checklist Development: We developed the first iteration of the checklist
      after review of the relevant literature and on the basis of the authors' clinical
      experience. Next, a panel of six content experts participated in three rounds of
      Delphi review to reach consensus on the final checklist items. Checklist
      Validation: Twenty-eight emergency medical services (EMS) providers (16 EMT
      Basics, 12 EMT-Paramedics) participated in a standardized simulated case of
      physical child abuse to an infant followed by one-on-one semi-structured
      qualitative interviews. Three reviewers scored the videotaped performance using
      the final checklist. Light's kappa and Cronbach's alpha were calculated to assess
      inter-rater reliability (IRR) and internal consistency, respectively. The
      correlation of successful child abuse screening with checklist task completion
      and with participant characteristics were compared using Pearson's chi squared
      test to gather evidence for construct validity. RESULTS: The Delphi review
      process resulted in a final checklist that included 24 items classified with
      trichotomous scoring (done, not done, or not applicable). The overall IRR of the
      three raters was 0.70 using Light's kappa, indicating substantial agreement.
      Internal consistency of the checklist was low, with an overall Cronbach's alpha
      of 0.61. Of 28 participants, only 14 (50%) successfully screened for child abuse
      in simulation. Participants who successfully screened for child abuse did not
      differ significantly from those who failed to screen in terms of training level,
      past experience with child abuse reporting, or self-reported confidence in
      detecting child abuse (all p > 0.30). Of all 24 tasks, only the task of exposing
      the infant significantly correlated with successful detection of child abuse (p <
      0.05). CONCLUSIONS: We developed a child abuse checklist that demonstrated strong
      content validity and substantial inter-rater reliability, but successful item
      completion did not correlate with other markers of provider experience. The
      validated instrument has important potential for training, continuing education,
      and research for prehospital providers at all levels of training.

PMID- 27700210
TI  - Effects of Boron-Based Gel on Radiation-Induced Dermatitis in Breast Cancer: A
      Double-Blind, Placebo-Controlled Trial.
AB  - AIM: This study is aimed to evaluate the effects of boron on radiation-induced
      skin reactions (RISR) in breast cancer patients. MATERIAL AND METHODS: After 47
      patients with invasive ductal carcinoma underwent radiotherapy, 23 (49%) received
      a boron-based gel, and 24 (51%) received placebo. Assessments were performed
      according to the Radiation Therapy Oncology Group (RTOG) skin scale and a Five
      Point Horizontal Scale (FPHS). RESULTS: At the end of the fifth week of
      radiotherapy, the RTOG scores in the boron group were significantly lower than
      those in the placebo group (p = .024). The FPHS score was higher in the placebo
      group than in the boron group, and this difference was not statistically
      significant (p = .079). CONCLUSION: Using the RTOG scoring system, we revealed
      that the application of a boron-based gel diminished RISR. The mechanism of
      action is unclear but may be related to antioxidant, wound healing, and thermal
      degradation effects of boron.

PMID- 27700212
TI  - New jobs.
AB  - Denise Chaffer has been appointed director of nurse education and professional
      development at St George's Hospital, London. She has been on secondment to the
      hospital from the RCN, where she was student adviser.

PMID- 27700211
TI  - Primary Biliary Cholangitis: Medical and Specialty Pharmacy Management Update.
AB  - BACKGROUND: Chronic liver disease and cirrhosis are a leading cause of morbidity
      and mortality in the United States. Primary biliary cholangitis (PBC), previously
      known as primary biliary cirrhosis and which has been designated an orphan
      condition, is a chronic autoimmune disease resulting in the destruction of the
      small bile ducts in the liver. Without effective treatment, disease progression
      frequently leads to liver failure and death. Until May 2016, the only FDA
      approved treatment for PBC was ursodiol (UDCA), an oral hydrophilic bile acid,
      which can slow progression of liver damage due to PBC. However, 1 out of 3
      patients taking UDCA has an inadequate biochemical response, leading to increased
      risk of disease progression, liver transplantation, and mortality. Given this
      unmet clinical need, new therapies are in development for the treatment of PBC.
      To provide pharmacists with an overview of the latest research on the
      pathophysiology of PBC and potential new treatment options and to highlight
      medical and specialty pharmacy approaches to managing access to drugs to treat
      orphan diseases such as PBC, a 2-hour satellite symposium was presented in
      conjunction with the 2015 Academy of Managed Care Pharmacy (AMCP) Nexus meeting.
      Although obeticholic acid was approved by the FDA for the treatment of PBC in May
      2016, this development occurred after the symposium presentation. The symposium
      was supported by an independent educational grant from Intercept Pharmaceuticals
      and was managed by Analysis Group. Robert Navarro, PharmD, moderated the CPE
      accredited symposium titled "Medical and Specialty Pharmacy Management Update on
      Primary Biliary Cirrhosis." Expert panelists included Christopher L. Bowlus, MD;
      James T. Kenney, RPh, MBA; and Gary Rice, RPh, MS, MBA, CSP. OBJECTIVE: To
      summarize the educational satellite symposium presentations and discussions.
      SUMMARY: Autoimmune liver diseases, including PBC, are responsible for 15% of all
      liver transplants performed and an equal percentage of deaths related to liver
      disease. UDCA is the only FDA-approved therapy for treatment of PBC and is
      considered the standard of care. Nevertheless, many patients do not respond to
      UDCA, creating the need for new therapeutic options to improve clinical outcomes
      for PBC patients with inadequate response to treatment. While several agents are
      being studied in combination with UDCA, monotherapy with the novel agent
      obeticholic acid, a farnesoid X receptor agonist, has also shown promising
      results. Health plans are anticipated to assign any newly introduced therapy for
      the treatment of PBC to specialty pharmacy given its orphan disease status. This
      assignment enables the health plan to receive disease education, which is
      particularly important when new drugs are indicated for orphan diseases, and
      assistance with designing appropriate prior authorization criteria. The clinical
      value of any new therapeutic options that will inform formulary decisions and
      prior authorization criteria will be assessed based on evidence of efficacy,
      safety, and tolerability, among other factors, such as the potential to reduce or
      delay medical resource utilization (e.g., liver transplant). Key considerations
      for prior authorization of a new therapy will be determining which PBC patients
      are appropriate candidates for the new therapy and developing criteria for that
      determination. These are likely to include clinical diagnostic criteria and
      degree of response to prior treatment with UDCA. Initially, any new therapy would
      likely be positioned as noncovered until appropriate prior authorization criteria
      are established. CONCLUSIONS: PBC is a chronic liver disease with significant
      morbidity and mortality, as well as a significant burden on the health care
      system if the disease progresses to the point at which a liver transplant is
      needed. Although UDCA, the current standard of care, has improved outcomes for
      many patients, others have an inadequate response to this treatment. This
      symposium discussed these issues and also addressed the overall treatment
      paradigm for orphan drug therapies, key implications for patient management, and
      the role of specialty pharmacy management and any associated needs both in
      general and specifically for new therapeutic options for PBC.

PMID- 27700213
TI  - Lack of resources no excuse says ombudsman.
AB  - The health service ombudsman's office has stressed that lack of resources will
      not automatically be accepted as an excuse for bad care. The Ombudsman, Michael
      Buckley, reported that his office received 2,595 complaints this year and
      investigated 241 of them.

PMID- 27700214
TI  - ?
AB  - It is very humbling to see ourselves as others see us, especially when one has to
      leave the country to hear the message. It was Paul Rasmussen, the Danish Prime
      Minister, berating Tony Blair at the opening ceremony of the ICN Quadrennial in
      Copenhagen recently that got things in perspective. 250 British nurses had made
      the trip so it was a good time to get the point across. Put simply, the Danish
      government, like many other governments around the world, are fed up with the UK
      recruiting nurses abroad instead of sorting out its problems at home.

PMID- 27700215
TI  - Election debrief.
AB  - SO NEW LABOUR are back in with another landslide. Is that good or bad for nurses
      and other health care workers? The answer depends very much on two factors, the
      first of which is dependent on the second.

PMID- 27700216
TI  - Leadership and politics.
AB  - WHATEVER MY VIEWS when I took up my present post, I am absolutely clear about my
      responsibilities as a senior civil servant. I shall not be talking about 'party
      politics'. Nor will I be spilling the beans about the politicians with whom I
      work!

PMID- 27700217
TI  - Racism is endemic within the NHS.
AB  - The biggest ever report of its kind has found that racism is endemic in the
      medical profession. The new report, Racism in Medicine just published by the
      King's Fund, argues that NHS managers should be more involved in recruitment
      processes as a way of tackling the problem.

PMID- 27700218
TI  - New ministers.
AB  - Jacqui Smith has been appointed health minister, replacing John Denham after his
      transfer to the Home Office.

PMID- 27700219
TI  - Stress levels increase for senior nurses.
AB  - Staff shortages, fears about safety and worries about the competency of agency
      staff are serious sources of stress among ward sisters and charge nurses, a
      report from the Policy Studies Institute has found.

PMID- 27700220
TI  - Evaluating a system of shared governance.
AB  - THE IMPLEMENTATION of process of shared governance took nine months. Specifically
      the focus was upon successfully implementing a structure that would allow all
      professional staff groups to become actively involved in strategic development,
      and that first and foremost they were instrumental in addressing issues that have
      a direct effect on patient care. With the advent of clinical governance, it was
      timely for the trust to ensure that the staff it employs were involved in
      management issues and managers became more involved with clinical processes.

PMID- 27700221
TI  - Queuing for care.
AB  - THE NHS PLAN aims to move the NHS from the mid 20th century to the 21st century (
      DoH 2000 ). It aims to change the culture of the NHS from a bureaucracy
      insensitive to the needs of people it serves, to one that is customer-focussed.
      This will involve radical changes to the NHS culture and it is unlikely that
      those changes can be implemented quickly ( Nazarko, 1996 ). It acknowledges the
      structural problems inherent in the NHS and aims to deliver a quality service.
      Does the NHS Plan give professionals the tools to deliver a quality service? How
      will other social policy initiatives help or hinder professionals in their
      efforts? Let us examine the potential benefits and pitfalls.

PMID- 27700222
TI  - Developing a learing culture.
AB  - A KEY ELEMENT to retaining and recruiting a nursing workforce is making sure that
      nurses are empowered to develop their practice and that they know their managers
      and other health professionals value their work. Although patients and relatives
      may well be effusive in their thanks to nurses, which in itself is an important
      aspect for job satisfaction, it is not enough.

PMID- 27700223
TI  - Steroid hormone receptors silence genes by a chromatin-targeted mechanism similar
      to those used for gene activation.
AB  - How genes are repressed by steroid hormones remains a matter of debate, and
      several indirect mechanisms have been proposed. We found that the ligand
      activated progesterone receptor recruits to the promoter of downregulated genes a
      repressor complex composed of HP1gamma, the lysine demethylase LSD1, histone
      deacetylases, coREST, the RNA SRA, and the ATPase BRG1. BRG1 is needed for
      chromatin remodeling and facilitates the deposition of linker histone variant
      H1.2, which compacts chromatin and hinders RNA polymerase loading and
      transcription. Thus, steroid hormone receptors can repress genes in ways
      reminiscent of those used for gene induction, namely by directly targeting
      factors that remodel chromatin. But while PR-dependent gene induction in T47D
      cells is mainly achieved by potentiating enhancer activity, repression acts at
      the level of gene promoters.

PMID- 27700224
TI  - Evidence-Based Treatment of Diabetic Retinopathy.
AB  - Diabetic retinopathy (DR) is the most frequent microvascular complication from
      diabetes and requires annual screening and at least annual follow-up. A systemic
      approach to optimize blood glucose and blood pressure may halt progression to
      severe stages of DR and obviate the need for ocular treatment. Although there is
      evidence of benefit from fenofibrate or intravitreous antiVEGF treatment for eyes
      with nonproliferative DR (NPDR), these therapies are not standard care for NPDR
      at this time. Some patients with severe NPDR, especially those with type 2
      diabetes, benefit from early panretinal photocoagulation (PRP). Once DR
      progresses to proliferative DR (PDR), treatment is often necessary to prevent
      visual loss. PRP remains mainstay treatment for PDR with high-risk
      characteristics. However, intravitreous antiVEGF injections appear to be a safe
      and effective treatment alternative for PDR through at least two years.
      Vitreoretinal surgery is indicated for PDR cases with non-clearing vitreous
      hemorrhage and/or tractional retinal detachment.

PMID- 27700225
TI  - NEAT1-containing paraspeckles: Central hubs in stress response and tumor
      formation.

PMID- 27700227
TI  - The response of soybean to nod factors and a bacteriocin.
AB  - Microbe-to-plant signals can enhance the growth of a wide range of crops. The
      responses by soybean (Glycine max var. 91M01) to 2 signal molecules were
      investigated: Bradyrhizobium japonicum 532C lipo-chitooligosaccharide (Nod Bj V
      [C:18, MeFuc]) (LCO); and Bacillus thuringiensis strain NEB17 bacteriocin
      thuricin 17 (Th17). The objective was to assess and quantify the response by
      soybean, in terms of factors that contribute to yield, to the experimental signal
      molecules in germination experiments and field experiments. Soybean germination
      was stimulated by the experimental concentrations of Th17 under controlled 15
      degrees C and 22 degrees C conditions, and 10-6 M LCO under 15 degrees C. There
      were negative relationships between Th17 concentration and both the number of
      trifoliate leaves and the dry weight of nodules: lower concentrations resulted in
      plants with more leaves and nodules while higher concentrations resulted in
      plants with fewer leaves and nodules. The 10-8 M LCO treatment had a significant
      effect on the dry weight of nodules at the flowering stage of plant development
      (F4,21 = 6.06, p = 0.0019). Considering the harvest stage data from both field
      trials of 2011, the lower experimental concentrations of Th17 resulted in taller
      plants. The study of Th17 has the potential to expand our understanding of this
      relatively recent and unexpected finding; and to understand how best to apply
      this finding, to allow increased production of soybean. Collectively, these
      results indicate that Th17 has potential in this regard.

PMID- 27700228
TI  - High-intensity interval training programme for obese youth (HIP4YOUTH): A pilot
      feasibility study.
AB  - Recently, there has been growing interest in high-intensity interval training
      (HIT) as a strategy to improve health. In this pilot study, we examined the
      feasibility of a 4-week low-volume HIT and its effects on cardiorespiratory
      fitness (CRF), blood pressure (BP) and enjoyment in overweight and obese youth.
      Twelve adolescents (body mass index (BMI): 34.8 +/- 3.9 kg . m-2, 14.9 +/- 1.5
      years) participated in 12 sessions of HIT (10 * 60 s cycling bouts eliciting ~90%
      maximal heart rate, interspersed with 90 s recovery, 30 min/session, 3
      sessions/week) over ~4 weeks. All the participants completed the study and
      exercise attendance averaged 92%. Despite no changes in body weight and total
      fat, HIT resulted in significant (P < 0.01) increases in CRF (pre: 20.1 versus
      post: 22.2 ml . kg-1 . min-1) and exercise time (pre: 425 versus post: 509 s)
      during peak oxygen uptake test, and a reduction in resting systolic BP (pre:
      115.8 versus post: 107.6 mmHg). The majority of study participants (83%) enjoyed
      HIT and more than half of the participants (58%) reported that HIT is a more
      enjoyable form of exercise compared to other types of exercises. Low-volume HIT
      is a useful strategy to promote exercise participation and improve cardiovascular
      health in overweight and obese youth.

PMID- 27700229
TI  - Breast Cancer Heterogeneity: MR Imaging Texture Analysis and Survival Outcomes.
AB  - Purpose To determine the relationship between tumor heterogeneity assessed by
      means of magnetic resonance (MR) imaging texture analysis and survival outcomes
      in patients with primary breast cancer. Materials and Methods Between January and
      August 2010, texture analysis of the entire primary breast tumor in 203 patients
      was performed with T2-weighted and contrast material-enhanced T1-weighted
      subtraction MR imaging for preoperative staging. Histogram-based uniformity and
      entropy were calculated. To dichotomize texture parameters for survival analysis,
      the 10-fold cross-validation method was used to determine cutoff points in the
      receiver operating characteristic curve analysis. The Cox proportional hazards
      model and Kaplan-Meier analysis were used to determine the association of texture
      parameters and morphologic or volumetric information obtained at MR imaging or
      clinical-pathologic variables with recurrence-free survival (RFS). Results There
      were 26 events, including 22 recurrences (10 local-regional and 12 distant) and
      four deaths, with a mean follow-up time of 56.2 months. In multivariate analysis,
      a higher N stage (RFS hazard ratio, 11.15 [N3 stage]; P = .002, Bonferroni
      adjusted alpha = .0167), triple-negative subtype (RFS hazard ratio, 16.91; P <
      .001, Bonferroni-adjusted alpha = .0167), high risk of T1 entropy (less than the
      cutoff values [mean, 5.057; range, 5.022-5.167], RFS hazard ratio, 4.55; P =
      .018), and T2 entropy (equal to or higher than the cutoff values [mean, 6.013;
      range, 6.004-6.035], RFS hazard ratio = 9.84; P = .001) were associated with
      worse outcomes. Conclusion Patients with breast cancers that appeared more
      heterogeneous on T2-weighted images (higher entropy) and those that appeared less
      heterogeneous on contrast-enhanced T1-weighted subtraction images (lower entropy)
      exhibited poorer RFS. (c) RSNA, 2016 Online supplemental material is available
      for this article.

PMID- 27700230
TI  - Rebuttal: near-infrared spectroscopy derived forearm oxygenation does predict
      rock climbing performance.

PMID- 27700226
TI  - LncRNAs: Bridging environmental sensing and gene expression.
AB  - The survival of all organisms is dependent on complex, coordinated responses to
      environmental cues. Non-coding RNAs have been identified as major players in
      regulation of gene expression, with recent evidence supporting roles for long non
      coding (lnc)RNAs in both transcriptional and post-transcriptional control.
      Evidence from our laboratory shows that lncRNAs have the ability to form
      hybridized structures called R-loops with specific DNA target sequences in S.
      cerevisiae, thereby modulating gene expression. In this Point of View, we provide
      an overview of the nature of lncRNA-mediated control of gene expression in the
      context of our studies using the GAL gene cluster as a model for controlling the
      timing of transcription.

PMID- 27700231
TI  - Frequency of Prosthetic Complications Related to Implant-Borne Prosthesis in a
      Sleep Disorder Unit.
AB  - Sleep bruxism and higher clench index have been associated with obstructive sleep
      apnea (OSA). However, there is no study that reports on the prosthetic
      complications in patients with OSA. Records of patients who had performed a sleep
      study to diagnose OSA were examined for the occurrence of prosthetic
      complications in implant-borne reconstructions. The primary outcome was the
      frequency of prosthetic complications. The secondary outcomes were anthropometric
      data, type of complication, type of prosthesis, type of retention, number of
      supporting implants, number of prosthetic units, and the presence of obstructive
      sleep apnea. Of the 172 patients, 67 had an implant-supported prosthesis, and all
      were included in the study. The mean age was 61 +/- 10 years, and 36 were female.
      Thirty complications in 22 prostheses were identified in 16 patients. The
      complications were porcelain fracture (14 events), screw/implant fracture (8
      events), screw loosening (3 events), and decementation (5 events). The follow-up
      time was 117 +/- 90 months after placement of the prosthesis. The average time
      for complications to occur was 73 +/- 65 months after the placement of the
      prosthesis. According to the apnea-hypopnea index (AHI), 49 patients had OSA.
      Thirteen of the 16 patients having a prosthetic complication also had OSA. The
      highest AHI and thus the severity of OSA was identified in patients with a
      fracture complication related to an implant, a screw, or a porcelain. The
      frequency of prosthetic complications has been higher in patients with
      obstructive sleep apnea.

PMID- 27700232
TI  - Distribution and Prevalence of Haemosporidian Parasites in the Northern Cardinal
      (Cardinalis cardinalis).
AB  - Avian haemosporidian parasites provide a model system for understanding
      ecological and evolutionary host-parasite interactions. The diversity and
      distribution of these parasites remains incomplete, and, here, we provide the
      first range-wide assessment of avian haemosporidians in a continentally
      distributed host, the Northern Cardinal ( Cardinalis cardinalis ). Based on
      molecular techniques, we show geographical differences in prevalence and lineage
      diversity between host subspecies and identify several novel lineages. We use
      phylogenetic reconstruction to show where these lineages fit into the expanding
      evolutionary tree of avian haemosporidian lineages. All except 1 subspecies of
      Northern Cardinal are highly parasitized by a wide diversity of Plasmodium and
      Parahaemoproteus. Compared to published studies that used microscopy to determine
      prevalence in this host, we find a much higher number of infected individuals
      (67.4% vs. 45% or less). Consistent with previous studies, Parahaemoproteus from
      the Northern Cardinal was found to be highly host specific and geographically
      structured, whereas Plasmodium was less host specific and geographically
      unstructured.

PMID- 27700233
TI  - Demystifying supervision.
AB  - THERE ARE problems in applying the existing models of supervision to the
      hierarchical organisation of the NHS ( Grant 2000 ). Despite the vast volume of
      literature offering 'models of supervision' few give an operational definition of
      the concept ( Wolsey and Leach 1997 ). The majority of these models frame
      supervision within a psychotherapeutic model where a fixed amount of supervision,
      either one-to-one or in a group, meets the needs ofthe supervisee until the next
      meeting. The 'supervision session' becomes an almost mystical experience with
      little reference to day-to-day life in a busy health service. Managers,
      colleagues and even demanding patients fade into the background.

PMID- 27700234
TI  - Conducting a process consultancy.
AB  - THIS SERIES on consultancy has to date focused upon 'purchase of expertise' forms
      of consultancy work. Simply put, this means that the consultant is hired to
      provide particular advice and the consultee(s) decides what to do with the
      recommendations that are made. In this form of consultancy the consultee retains
      executive responsibility, both shaping the terms of reference for the project and
      how to respond to the consultancy report. There are occasions, however, when a
      different approach to change seems more apt ( Berragan 1998 , Price 1997 ).

PMID- 27700235
TI  - Scottish solutions.
AB  - The next election for the Scottish parliament is still three years away. This has
      meant that the initial scepticism which greeted the NHS Plan in England, with
      cries of: 'it's an election manifesto', has not been so marked. But now the
      English Plan is in place it is widely regarded as bringing some workable
      solutions to difficult problems. So how will the Scottish Plan measure up?

PMID- 27700236
TI  - Massive increase in reported violence against NHS staff.
AB  - Violence against NHS staff has increased by 22 per cent over the last year,
      according to a survey by the Health Service Report.

PMID- 27700237
TI  - NHS Plan Wales.
AB  - Following the high profile launch of the English NHS Plan last summer, there has
      been speculation in Wales about whether we too would have a Plan. Jane Hutt the
      Welsh Assembly's minister for health became rather defensive after the launch of
      the English Plan. She accused journalists of posing awkward questions about the
      lack of a Welsh Plan, of not understanding devolution, and explained that
      governments in different parts of the UK could and would package their health
      policies differently. In one respect she was right; journalists, either side of
      the border, do not understand devolution. In another respect she was wrong; the
      Welsh government, rather predictably, did package their health policy in much the
      same way as had been done in England, and our Welsh NHS Plan was launched earlier
      this month, supported by an additional L1billion over three years.

PMID- 27700239
TI  - Speak out loud for nursing.
AB  - SEVERAL MONTHS AGO we made a presentation on public communication for nurses at a
      major hospital. An intensive care unit nurse manager approached us with a
      dilemma. She wanted to secure more resources to support nursing. To get these
      resources, however, top hospital administrators needed to better understand the
      importance of nursing. She wanted ICU nurses to speak with administrators and
      describe their contributions to patient care.

PMID- 27700238
TI  - New jobs.
AB  - ? Sue Plummer will represent nurses on the Care Development Group set up by the
      Scottish Executive last week to look at how free personal care should be provided
      north of the border. Ms Plummer is nurse director at Borders Primary Care Trust
      and a former nursing officer in the Scottish Office. She joins an 11-strong body
      of experts to be chaired by deputy health minister Malcolm Chisholm.

PMID- 27700240
TI  - Calls to withdraw Clause 59.
AB  - Professional bodies have raised wide spread concerns about the implications of
      Clause 59 of the Health and Social Care Bill. The clause gives the Secretary of
      State for Health considerable powers over how patients' medical data is shared.

PMID- 27700241
TI  - Developing a fair use of resourcesThe recent British Medical Association report,
      Healthcare Funding Review ( BMA 2001 ), has thrown the issue of healthcare
      rationing into the spotlight again. Margaret Goodman looks at attempts to
      prioritise healthcare in other countries and draws lessons for the UK.
AB  - The UK is not alone in facing increased pressures on health care within the
      context of finite resources. So is there is anything to be learned from the
      experiences of other countries and should their methods be adopted for the NHS?

PMID- 27700242
TI  - Clinical leadership that works.
AB  - DEVELOPING CLINICAL nurse leaders is a major priority in the health service
      today. Following a study tour of three states in Australia, I believe we have a
      great deal to learn by studying their approach. I visited New South Wales,
      Victoria and Queensland, within each state I spent time in both rural and
      metropolitan health care settings.

PMID- 27700243
TI  - Innovate and prosper.
AB  - ALL HEALTH care organisations have a need to innovate. It enables them to deal
      with the changing forms of disease, technological developments and demography.
      Research-led developments, with great value placed on clinical interventions,
      still occupy centre stage and little attention is given to management
      interventions and in particular to the evaluation of innovations. ( Drummond et
      al 1987 , Drummond 1990 , McCloskey et al 1994 ).

PMID- 27700244
TI  - Active self-correction of spinal posture in pain-free women in response to the
      command "straighten your back".
AB  - Evidence is limited regarding the regional changes in spinal posture after self
      correction. The aim of the present study was to evaluate whether active self
      correction improved standing and sitting spinal posture. Photogrammetry was used
      to assess regional spinal curvatures and vertical global spine orientation (GSO)
      in 42 asymptotic women aged 20-24 years. Upper thoracic spine angle and GSO
      increased in response to self-correction, while the thoracolumbar and lumbosacral
      angles decreased. Self-correction in the standing position resulted in decreased
      inclination of the upper thoracic and thoracolumbar spinal angles. Correction of
      sitting posture reduced the angle of the upper thoracic spine and GSO. The
      effects of active self-correction on spinal curvature and GSO were different for
      the standing versus sitting position; the greatest effects of active correction
      were noted in the thoracic spine. Balanced and lordotic postures were most
      prevalent in the habitual and actively self-corrected standing positions, whereas
      the kyphotic posture was most prevalent in the habitual sitting position,
      indicative that self-correction back posture in the standing position could be an
      important health-related daily activity, especially during prolonged sitting.

PMID- 27700245
TI  - Differences between native and immigrant women in Taiwan in factors associated
      with caesarean section: A prospective observational study.
AB  - This study aimed to examine the association of social support, social factors,
      and maternal complications with caesarean deliveries in native and immigrant
      women, and to explore the association between acculturation and caesarean
      deliveries in immigrant women in Taiwan. This prospective panel study was
      conducted from August 2012 through April 2014 and included 222 native and 147
      immigrant pregnant women in Taiwan. Caesarean rates did not differ significantly
      between native and immigrant women, including the overall caesarean rate (28.8%,
      32.0%), medically indicated caesarean (22.5%, 24.5%), and caesarean without
      medical indications (6.3%, 7.5%). Results of multiple logistic regression models
      revealed that maternal complications and household activity support were
      positively associated with caesarean deliveries. Both native and immigrant women
      with high levels of informational support were less likely to receive caesareans.
      Immigrant women who were older than 35 years, had a middle level socioeconomic
      status, and perceived a high level of acceptance of caesarean in Taiwan were more
      likely to have caesarean deliveries. Informational support was a protective
      factor for caesarean delivery, whereas household activity support offered by the
      family was positively associated with caesarean delivery. Perceived acceptance
      level in mainstream society could affect immigrant women's use of caesarean
      delivery.

PMID- 27700248
TI  - Teaching and Learning in Medicine Volume 28, 2016.

PMID- 27700247
TI  - Coming in From the Cold-Physician Professional Development as Deepening
      Participation in the Healthcare Community.
AB  - This Conversation Starters article presents a selected research abstract from the
      2016 Association of American Medical Colleges Southern Region Group on
      Educational Affairs annual spring meeting. The abstract is paired with the
      integrative commentary of three experts who shared their thoughts stimulated by
      the pilot study. These thoughts probe the concept of patient "ownership" and
      suggest an alternative way of conceptualizing physicians' total dedication to
      patient care.

PMID- 27700249
TI  - On the Origins of Perceptions: Student Perceptions of Active Learning and Their
      Implications for Educational Reform.
AB  - This Conversation Starters article presents a selected research abstract from the
      2016 Association of American Medical Colleges Central Region Group on Educational
      Affairs annual spring meeting. The abstract is paired with the integrative
      commentary of three experts who shared their thoughts stimulated by the study.
      These thoughts highlight the value of exploring what drives student perceptions
      of active learning in order to reform medical education.

PMID- 27700250
TI  - Exploring the Role of Peer Advice in Self-Regulated Learning: Metacognitive,
      Social, and Environmental Factors.
AB  - This Conversation Starters article presents a selected research abstract from the
      2016 Association of American Medical Colleges Northeast Region Group on
      Educational Affairs annual spring meeting. The abstract is paired with the
      integrative commentary of three experts who shared their thoughts stimulated by
      the pilot study. These thoughts explore the metacognitive, social, and
      environmental mechanisms whereby advice plays a role in self-regulated learning.

PMID- 27700252
TI  - Done or Almost Done? Improving OSCE Checklists to Better Capture Performance in
      Progress Tests.
AB  - : Construct: The impact of using nonbinary checklists for scoring residents from
      different levels of training participating in objective structured clinical
      examination (OSCE) progress tests was explored. BACKGROUND: OSCE progress tests
      typically employ similar rating instruments as traditional OSCEs. However,
      progress tests differ from other assessment modalities because learners from
      different stages of training participate in the same examination, which can pose
      challenges when deciding how to assign scores. In an attempt to better capture
      performance, nonbinary checklists were introduced in two OSCE progress tests. The
      purposes of this study were (a) to identify differences in the use of checklist
      options (e.g., done satisfactorily, attempted, or not done) by task type, (b) to
      analyze the impact of different scoring methods using nonbinary checklists for
      two OSCE progress tests (nonprocedural and procedural) for Internal Medicine
      residents, and (c) to determine which scoring method is better suited for a given
      task. APPROACH: A retrospective analysis examined differences in scores (n = 119)
      for two OSCE progress tests (procedural and nonprocedural). Scoring methods
      (hawk, dove, and hybrid) varied in stringency in how they awarded marks for
      nonbinary checklist items that were rated as done satisfactorily, attempted, or
      not done. Difficulty, reliability (internal consistency), item-total correlations
      and pass rates were compared for each OSCE using the three scoring methods.
      RESULTS: Mean OSCE scores were highest using the dove method and lowest using the
      hawk method. The hawk method resulted in higher item-total correlations for most
      stations, but there were differences by task type. Overall score reliability
      calculated using the three methods did not differ significantly. Pass-fail status
      differed as a function of scoring methods and exam type, with the hawk and hybrid
      methods resulting in higher failure rates for the nonprocedural OSCE and the dove
      method resulting in a higher failure rate for the procedural OSCE. CONCLUSION:
      The use of different scoring methods for nonbinary OSCE checklists resulted in
      differences in mean scores and pass-fail status. The results varied with
      procedural and nonprocedural OSCEs.

PMID- 27700251
TI  - What's in a Transition? An Integrative Perspective on Transitions in Medical
      Education.
AB  - This Conversation Starters article presents a selected research abstract from the
      2016 Association of American Medical Colleges Western Region Group on Educational
      Affairs annual spring meeting. The abstract is paired with the integrative
      commentary of three experts who shared their thoughts stimulated by the needs
      assessment study. These thoughts explore how the general theoretical mechanisms
      of transition may be integrated with cognitive load theory in order to design
      interventions and environments that foster transition.

PMID- 27700253
TI  - Keeping the Conversation Going.

PMID- 27700254
TI  - JSCM Welcomes You To Miami.

PMID- 27700255
TI  - Message From the President.

PMID- 27700256
TI  - Message From the President-Elect.

PMID- 27700257
TI  - Invitational Lectureships, Lifetime Achievement Award, Synthes Spine Award.

PMID- 27700258
TI  - Helping The Body To Cure Itself: Immune Modulation By Therapeutic Vaccination For
      Spinal Cord Injury.
AB  - Spinal cord injury often has devastating consequences, due to the poor
      regenerative capacity of the central nervous system (CNS), and because the injury
      triggers self-destructive processes that lead to degeneration of directly injured
      fibers, and fibers that survived the lesion but subsequently undergo "secondary
      degeneration." The highly complex, multifaceted dialogue between the immune
      system and the damaged spinal cord is complicated further by factors related to
      species, strain, and gender. It is suggested that following an injury to the CNS,
      the resident and systemic immune cells are recruited and activated, to reduce the
      self-destruction and facilitate the repair of the damaged nerve. Both of these
      functions can benefit from a well-controlled immune response that critically
      involves the innate and adaptive arms of the immune system, represented by
      macrophages/ microglia and autoimmune T cells, respectively. A poorly controlled
      immune response can be non-efficient or even destructive, leading in extreme
      cases even to autoimmune disease. The beneficial autoimmune response can be
      boosted by posttraumatic T cell-based vaccination with peptides that activate
      weak self-reactive T cells, thereby ensuring timely and adequate immune
      activation without the risk of autoimmune disease. It is proposed that the notion
      of "bad" or "good" inflammation be replaced by a concept that views inflammation
      in the CNS as a repair mechanism and thus as beneficial if well regulated, and
      supports therapy for spinal cord and other CNS injuries by immunomodulation.

PMID- 27700261
TI  - Poster Presentations.

PMID- 27700260
TI  - American Spinal Injury Association 29th Annual Scientific Meeting Award-Winning
      Abstracts 2003.

PMID- 27700262
TI  - Fine-Tuning The Neurological Classification Of Spinal Cord Injury: The Sixth
      Edition.

PMID- 27700263
TI  - Multiple gastric erosions diagnosed by means of capsule endoscopy in a dog.
AB  - CASE DESCRIPTION A 6-year-old spayed female Golden Retriever was evaluated for a
      2-week history of progressive hyporexia, signs of abdominal pain, and weight
      loss. CLINICAL FINDINGS Physical examination findings included mild signs of pain
      on palpation of the cranial part of the abdomen and a body condition score of 4
      (scale, 1 to 9). A CBC revealed mild microcytosis and hypochromasia; results of
      serum biochemical analysis were within the respective reference ranges, and
      abdominal ultrasonography revealed no abnormalities. Capsule endoscopy was
      performed, and numerous gastric erosions and hemorrhages were detected, with rare
      dilated lacteals in the proximal aspect of the small intestine. TREATMENT AND
      OUTCOME Treatment was initiated with omeprazole and sucralfate for 6 weeks, and
      the dog was transitioned to a novel protein diet. Capsule endoscopy was repeated
      at the end of the initial treatment course and revealed overall improvement, with
      a few small erosions remaining; medical treatment was continued for an additional
      2 weeks. At last follow-up 9 months after treatment ended, the dog was clinically
      normal. CLINICAL RELEVANCE Capsule endoscopy was useful for initial detection and
      subsequent reevaluation of gastrointestinal lesions in this patient without a
      need for sedation or anesthesia. Information obtained in the follow-up evaluation
      was valuable in identifying a need to extend the duration of medical treatment.

PMID- 27700264
TI  - Pathology in Practice.

PMID- 27700265
TI  - Rigid urethrocystoscopy via a percutaneous fluoroscopic-assisted perineal
      approach in male dogs: 19 cases (2005-2014).
AB  - OBJECTIVE To describe the technique and outcome for male dogs undergoing rigid
      urethrocystoscopy via a novel percutaneous, fluoroscopic-assisted perineal
      approach. DESIGN Retrospective case series. ANIMALS 19 client-owned male dogs.
      PROCEDURES Medical records of male dogs that underwent urethrocystoscopy via a
      percutaneous perineal approach for treatment of a variety of conditions from 2005
      through 2014 were reviewed. Signalment, history, pertinent diagnostic imaging
      results, endourologic and postprocedure details, duration of hospitalization,
      complications, and outcome (short-term, < 1 month; long-term, >= 1 month) were
      recorded. After flexible urethrocystoscopy, direct percutaneous perineal needle
      puncture and guidewire placement by means of fluoroscopic guidance (with or
      without ultrasonography) allowed access to the urethral lumen. The perineal tract
      was subsequently serially dilated to accommodate a peel-away sheath and rigid
      endoscope. Rigid urethrocystoscopy was performed, and on completion of
      endourologic procedures, the access site was left to heal by second intention.
      RESULTS 19 male dogs successfully underwent 20 procedures. No intraoperative
      complications were reported. Short-term outcome was good (ie, mild perineal urine
      leakage) for 3 dogs and excellent (ie, no abnormalities with urination) for 16.
      Long-term outcome was excellent for the 17 dogs for which follow-up information
      was available. CONCLUSIONS AND CLINICAL RELEVANCE A percutaneous fluoroscopic
      assisted perineal approach (with or without ultrasonography) allowed access to
      the pelvic urethra with no major complications in the present series of patients.
      This minimally invasive approach may be a valuable tool for endourologic
      procedures in male dogs.

PMID- 27700266
TI  - Epidemiological, clinical, and echocardiographic features and survival times of
      dogs and cats with tetralogy of Fallot: 31 cases (2003-2014).
AB  - OBJECTIVE To characterize the epidemiological, clinical, and echocardiographic
      features of dogs and cats with tetralogy of Fallot (TOF) and determine their
      survival times. DESIGN Retrospective case series. ANIMALS 15 dogs and 16 cats
      with a diagnosis of TOF as determined via echocardiography. PROCEDURES Medical
      records of dogs and cats were reviewed to extract information on signalment,
      clinical status at the time of TOF diagnosis, echocardiographic findings, and any
      outcome data. RESULTS The most common canine breeds were terrier types (n = 7).
      Most animals (28/31 [90%]) had clinical signs of TOF at the time of diagnosis,
      including cyanosis (16/31 [52%]). Pulmonic stenosis was characterized by a
      variable systolic Doppler-derived pressure gradient (median [range], 108 mm Hg
      [26 to 255 mm Hg]). Most ventricular septal defects were large, with a median
      (range) ratio of the diameter of the ventricular septal defect to that of the
      aorta of 0.60 (0.18 to 1.15). Median age at cardiac-related death was 23.4
      months, with no significant difference between dogs and cats. Median survival
      time from TOF diagnosis to cardiac-related death was briefer for animals with no
      or low-grade heart murmur (3.4 months) than for those with higher-grade heart
      murmur (16.4 months). After adjustment for age and sex, having a lack of or a low
      to mild-grade systolic heart murmur was significantly associated with a briefer
      survival time. CONCLUSIONS AND CLINICAL RELEVANCE With a few exceptions, cardiac
      related death occurred predominantly in young adult dogs and cats with TOF, and
      most animals had severe clinical signs at the time of TOF diagnosis.

PMID- 27700267
TI  - Objective assessment of the compensatory effect of clinical hind limb lameness in
      horses: 37 cases (2011-2014).
AB  - OBJECTIVE To characterize and describe the compensatory load redistribution that
      results from unilateral hind limb lameness in horses. DESIGN Retrospective case
      series. ANIMALS 37 client-owned horses. PROCEDURES Medical records were reviewed
      to identify horses with unilateral hind limb lameness that responded positively
      (by objective assessment) to diagnostic local anesthesia during lameness
      evaluation and that were evaluated before and after diagnostic local anesthesia
      with an inertial sensor-based lameness diagnosis system. Horses were grouped as
      having hind limb lameness only, hind limb and ipsilateral forelimb lameness, or
      hind limb and contralateral forelimb lameness. Measures of head and pelvic
      movement asymmetry before (baseline) and after diagnostic local anesthesia were
      compared. The effect of group on baseline pelvic movement asymmetry variables was
      analyzed statistically. RESULTS Maximum pelvic height significantly decreased
      from the baseline value after diagnostic local anesthesia in each of the 3
      lameness groups and in all horses combined. Minimum pelvic height significantly
      decreased after the procedure in all groups except the hind limb and
      contralateral forelimb lameness group. Head movement asymmetry was significantly
      decreased after diagnostic local anesthesia for horses with hind limb and
      ipsilateral forelimb lameness and for all horses combined, but not for those with
      hind limb lameness only or those with hind limb and contralateral forelimb
      lameness. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that hind limb
      lameness can cause compensatory load redistribution evidenced as ipsilateral
      forelimb lameness. In this population of horses, contralateral forelimb lameness
      was not compensatory and likely reflected true lameness. Further studies are
      needed to investigate the source of the contralateral forelimb lameness in such
      horses.

PMID- 27700268
TI  - Overdiagnosis.

PMID- 27700270
TI  - Letters to the Editor.

PMID- 27700269
TI  - What Is Your Neurologic Diagnosis?

PMID- 27700271
TI  - ECG of the Month.

PMID- 27700273
TI  - In This Issue * October 15, 2016.

PMID- 27700272
TI  - Risk factors associated with fatal injuries in Thoroughbred racehorses competing
      in flat racing in the United States and Canada.
AB  - OBJECTIVE To identify risk factors associated with fatal injuries in Thoroughbred
      racehorses in the United States and Canada. DESIGN Retrospective study. ANIMALS
      1,891,483 race starts by 154,527 Thoroughbred racehorses at 89 racetracks in the
      United States and Canada from 2009 to 2013. PROCEDURES Data were extracted from
      the Equine Injury Database, which contained information for 93.9% of all official
      flat racing events in the United States and Canada during the 5-year observation
      period. Forty-four possible risk factors were evaluated by univariate then
      multivariable logistic regression to identify those that were significantly
      associated with fatal injury (death or euthanasia of a horse within 3 days after
      sustaining an injury during a race). RESULTS 3,572 race starts ended with a fatal
      injury, resulting in a period incidence rate of 1.9 fatal injuries/1,000 race
      starts. Twenty-two risk factors were significantly associated with fatal injury.
      Risk of fatal injury was greater for stallions than for mares and geldings and
      increased as the number of previous nonfatal injuries and race withdrawals and
      level of competitiveness (eg, horse's winning percentage and race purse) of the
      horse or race increased. CONCLUSIONS AND CLINICAL RELEVANCE Results identified
      several risk factors associated with fatal injuries in Thoroughbred racehorses.
      This information can be used as a guideline for the identification of racehorses
      at high risk of sustaining a fatal injury and in the design and implementation of
      preventative measures to minimize the number of fatal injuries sustained by
      horses competing in flat racing in the United States and Canada.

PMID- 27700275
TI  - Pathology in Practice.

PMID- 27700276
TI  - Implementing wellness in the veterinary workplace.

PMID- 27700277
TI  - What Is Your Diagnosis?

PMID- 27700279
TI  - A Probabilistic Reformulation of No Free Lunch: Continuous Lunches Are Not Free.
AB  - No Free Lunch (NFL) theorems have been developed in many settings over the last
      two decades. Whereas NFL is known to be possible in any domain based on set
      theoretic concepts, probabilistic versions of NFL are presently believed to be
      impossible in continuous domains. This article develops a new formalization of
      probabilistic NFL that is sufficiently expressive to prove the existence of NFL
      in large search domains, such as continuous spaces or function spaces. This
      formulation is arguably more complicated than its set-theoretic variants, mostly
      as a result of the numerous technical complications within probability theory
      itself. However, a probabilistic conceptualization of NFL is important because
      stochastic optimization methods inherently need to be evaluated
      probabilistically. Thus the present study fills an important gap in the study of
      performance of stochastic optimizers.

PMID- 27700278
TI  - Introducing Elitist Black-Box Models: When Does Elitist Behavior Weaken the
      Performance of Evolutionary Algorithms?
AB  - Black-box complexity theory provides lower bounds for the runtime of black-box
      optimizers like evolutionary algorithms and other search heuristics and serves as
      an inspiration for the design of new genetic algorithms. Several black-box models
      covering different classes of algorithms exist, each highlighting a different
      aspect of the algorithms under considerations. In this work we add to the
      existing black-box notions a new elitist black-box model, in which algorithms are
      required to base all decisions solely on (the relative performance of) a fixed
      number of the best search points sampled so far. Our elitist model thus combines
      features of the ranking-based and the memory-restricted black-box models with an
      enforced usage of truncation selection. We provide several examples for which the
      elitist black-box complexity is exponentially larger than that of the respective
      complexities in all previous black-box models, thus showing that the elitist
      black-box complexity can be much closer to the runtime of typical evolutionary
      algorithms. We also introduce the concept of p-Monte Carlo black-box complexity,
      which measures the time it takes to optimize a problem with failure probability
      at most p. Even for small  p, the p-Monte Carlo black-box complexity of a
      function class [Formula: see text] can be smaller by an exponential factor than
      its typically regarded Las Vegas complexity (which measures the expected time it
      takes to optimize [Formula: see text]).

PMID- 27700281
TI  - Change management: a guide to effective implementation Change management: a guide
      to effective implementation Paton Robert ; McCalman James Sage 288pp L17.99 0
      7619 6499 076196499 [Formula: see text].
AB  - Change Management: A guide to effective implementation, written by Robert A Paton
      and James McCalman, is also a book that nurses will find extremely useful to
      supplement practical based learning. However, some may find that the style of
      writing inhibits their learning.

PMID- 27700282
TI  - Nurse nurse.

PMID- 27700283
TI  - Websites.

PMID- 27700284
TI  - Organisational management.
AB  - UNDER THE current wave of organisational change that is sweeping across the NHS
      nurses are working constantly to ensure that service users continue to receive
      high quality services, located in the right environment and delivered at the
      right time.

PMID- 27700285
TI  - Conferences.
AB  - 7-10 April 2002 University of Exeter, Exeter, UK RCN Research Society conference
      and seminars Details: Kathryn Clark, RCN assistant conference & events manager.
      Tel: 020 7647 3585 Email: research@rcn.org.uk Website: www.rcn.org.uk.

PMID- 27700286
TI  - Rehabilitation.
AB  - BUYING BEDS to accommodate people in need of rehabilitation is something of a
      balancing act, dependent on a number of factors.

PMID- 27700287
TI  - Resources.

PMID- 27700289
TI  - Action plan announced for Scotland.
AB  - The Scottish Executive has announced a package of measures to tackle recruitment
      and retention problems in Scotland. Following the nursing convention held last
      November, the Executive has published an action plan.

PMID- 27700288
TI  - Developing leadership through clinical supervision.
AB  - Last month the authors described the role of the nurse in the prison service, the
      need for clinical supervision, and the parameters for a project to implement a
      clinical supervision model in five prisons in England ( Freshwater et al 2001 ).
      Here, they examine some of the findings from the project, particularly in
      relation to practice, education and barriers to implementation.

PMID- 27700290
TI  - Editorial.
AB  - I am not sure that everyone working in health services is strong enough to live
      through the Prime Minister's promise to make public services his top priority for
      2002. For many, there is a sense that too much change is going on any way. It is
      a very uncertain framework to be operating within when so much of the command
      structure is in flux across the UK. There is the increasing impact of staff
      shortages, the lower level of revenue than expected, the hypothecation of budgets
      and the lack of clarity about the implications of policy directives.

PMID- 27700291
TI  - Leadership in the NHS leading at all levels.
AB  - STOKE MANDEVILLE Hospital NHS Trust in Aylesbury, Buckinghamshire, is a district
      general hospital with a busy maternity unit delivering around 2,700 babies a
      year.

PMID- 27700292
TI  - Developing and working in a group.
AB  - Many people find it helpful to work in small groups when they are solving
      problems. Dr Vivien Martin explains how to form your group and plan your work in
      a structured way. This article is based on the course 'Assessing Practice in
      Nursing and Midwifery' from the School of Health and Social Welfare at the Open
      University.

PMID- 27700293
TI  - New honours.
AB  - More than 30 nurses were recognised in the New Year honours list. Catherine
      Elcoat (pictured left, top), chief nurse at University Hospital Birmingham NHS
      Trust is to be made a dame and former RCN chair Debbie Murdock (left) is to
      receive an OBE. Other nurses to be honoured included.

PMID- 27700294
TI  - Vision of the future.
AB  - HEALTH AND Personal Social Services (HPSS) in Northern Ireland face potentially
      one of the most radical reorganisations since 1972 following publication last
      year of the Acute Hospitals Review.

PMID- 27700295
TI  - Mastering organisational behaviour Mastering organisational behaviour Pettinger
      Richard Macmillan Master Series 246pp L12.99 0 333 79279 3 0333792793 [Formula:
      see text].
AB  - If diagrammatic and pictorial learning is your preferred style you may find that
      Mastering Organisational Behaviour, written by Richard Pettinger, meets your
      needs. Throughout the book Pettinger uses diagrams, rather than case study
      examples, to help the reader understand the theory behind organisational
      behaviour.

PMID- 27700296
TI  - Nursing is bottom of league.
AB  - The results for the latest research assessment exercise (RAE) published last
      month show nursing departments still at the bottom of the league. Although the
      quality of research in nursing departments has improved, it remains the worst
      performer in 69 university disciplines.

PMID- 27700297
TI  - Nurse and midwife numbers rise.
AB  - Nurse and midwife numbers in the NHS have risen by 10,000 in the past year,
      according to figures released by the Department of Health in December. The net
      result, says the Department, is a rise of 27,000 since 1997 It also means that
      16,000 staff have already been recruited towards the NHS Plan target of 20,000 by
      2004.

PMID- 27700298
TI  - Nurse unions 'disappointed' by pay increase for 2002.
AB  - Nurse leaders and unions have reacted with disappointment to the 3.6 per cent pay
      increase for the profession announced before Christmas. Many believe the increase
      fails to close the gap between nurses and other public sector workers, such as
      police officers and teachers. They predict that as a result, recruitment and
      retention problems will continue to deepen.

PMID- 27700299
TI  - Shared governance from concept to reality.
AB  - THE CONCEPT of shared governance, which originated in the USA in the 1970s, has
      recently been introduced into Britain ( Geoghegan and Farrington 1995 ). It
      developed as a means of allowing staff nurses to have greater control over their
      working environment (Totten and Scott 1993) and is widely recognised as having
      benefits in empowering practitioners from a variety of health care professions (
      Porter O'Grady 1994 ). Several models of shared gov- ernance have been described
      in the literature (Porter-O'Grady 1994, Geoghegan and Farrington 1995), making it
      a broad philosophy which can be adapted to meet the needs of individual hospitals
      and health care trusts in the UK.

PMID- 27700300
TI  - Nursing the modern profession.
AB  - DURING THIS lecture I will be giving you my sense of where nursing is today and
      the many challenges and opportunities which that presents for all those engaged
      in the world of nursing and health care - and that is a pretty big stakeholder
      group.

PMID- 27700301
TI  - Conferences.

PMID- 27700302
TI  - OU launches pack to help mentors.
AB  - The Open University has launched a series of new materials aimed at nurses and
      midwives who act as mentors for students.

PMID- 27700303
TI  - The best is yet to come.
AB  - BEVERLEY STEPHENS was busy preparing to attend the Ashridge 'Strategy and
      Leadership' programme when I spoke with her. She had won the opportunity to
      attend this because she was the outstanding candidate in the RCN Leadership
      awards organised as part of the Nursing Standard Nurse of the Year competition in
      2000. She exudes determination, confidence and concern for colleagues, all with a
      quiet insightfulness about the potential weakness of organisations and human
      nature. Difficult to guess her age, she presents an inquiring front to the world,
      ever conscious of how her own experience has formed her.

PMID- 27700304
TI  - ?
AB  - One of the privileges of being the editor of Nursing Management is chairing
      events held in fields of nursing of which I have no particular understanding. One
      such event was the recent Prison Nurses' Conference.

PMID- 27700305
TI  - Mix and match.
AB  - Major reviews of workforce planning are presently taking place in Scotland (
      Scottish Executive 2000b ) and England ( Department of Health 2000 ). Due to the
      UK-wide nature of current NHS career structures and pay arrangements both reviews
      will be of interest and have implications for education and training. The
      Scottish Integrated Workforce Planning Group ( Scottish Executive 2000b )
      identified education and training as a factor affecting workforce planning and
      highlighted the need for a strong link at practical and policy levels between the
      two to be made explicit.

PMID- 27700306
TI  - New management consultancy.
AB  - A new healthcare management consultancy, Quo Health, has been launched with the
      backing of former parliamentary under-secretary of state Baroness Julia
      Cumberlege and a former chief executive in the NHS Anthony McKeever.

PMID- 27700307
TI  - New jobs.
AB  - Jacquie Scott has been appointed director of nursing and quality by Harrow and
      Hillingdon Healthcare NHS Trust, west London. Ms Scott specialised as an
      orthopaedic nurse in her clinical career and more recently was chief executive
      and nursing director at St Vincent's Hospital in Eastcote, north London.

PMID- 27700308
TI  - Huge increase in spending on nursing agencies.
AB  - The flexible healthcare staffing market has quadrupled in size since 1992, a new
      report by analysts Laing & Buisson has found. The flexible healthcare market,
      covering nursing agencies, other health- care staff agencies, doctor deputising
      and domicilliary care agencies was worth around 32.4 billion in 1999/2000.

PMID- 27700309
TI  - Learning to lead.
AB  - Effective clinical leadership has been central to the last government's
      modernisation agenda ( DoH 2000a ) and nursing has been one of the key groups
      targeted for development. Calls for the 'modern matron', for example, reflect the
      public desire for a named and accountable individual who will take responsibility
      for the quality of patients' experience and will intervene to make improvements
      where necessary.

PMID- 27700310
TI  - The Human Rights Act: What are the implications for older people?
AB  - Help the Aged is launching a report outlining the terms of the Human Rights Act
      and its implications both for older people themselves and for public bodies
      responsible for providing services to them. Tessa Harding, head of policy at Help
      the Aged said: 'The Human Rights Act is an important turning point for older
      people. Not only does it establish key rights of individuals to freedom from
      inhuman and degrading treatment, to private and family life and so on; it also
      prohibits discrimination in accessing these rights.We expect older people and
      their advocates to use the Act to ensure greater fairness and equality in our
      society.'

PMID- 27700311
TI  - Specialist nursing in MS - the way forward: key elements for developing MS
      specialist nurse services in the UK.
AB  - This publication has been developed by a panel of eminent specialists in the
      field of multiple sclerosis, including MS specialist nurses, NHS managers and the
      Royal College of Nursing, facilitated by the MS Research Trust.

PMID- 27700312
TI  - Alterations to the orientation of the ground reaction force vector affect sprint
      acceleration performance in team sports athletes.
AB  - A more horizontally oriented ground reaction force vector is related to higher
      levels of sprint acceleration performance across a range of athletes. However,
      the effects of acute experimental alterations to the force vector orientation
      within athletes are unknown. Fifteen male team sports athletes completed maximal
      effort 10-m accelerations in three conditions following different verbal
      instructions intended to manipulate the force vector orientation. Ground reaction
      forces (GRFs) were collected from the step nearest 5-m and stance leg kinematics
      at touchdown were also analysed to understand specific kinematic features of
      touchdown technique which may influence the consequent force vector orientation.
      Magnitude-based inferences were used to compare findings between conditions.
      There was a likely more horizontally oriented ground reaction force vector and a
      likely lower peak vertical force in the control condition compared with the
      experimental conditions. 10-m sprint time was very likely quickest in the control
      condition which confirmed the importance of force vector orientation for
      acceleration performance on a within-athlete basis. The stance leg kinematics
      revealed that a more horizontally oriented force vector during stance was
      preceded at touchdown by a likely more dorsiflexed ankle, a likely more flexed
      knee, and a possibly or likely greater hip extension velocity.

PMID- 27700375
TI  - Developing middle managers.
AB  - BOTH THE NURSING strategy for the NHS in England (DoH 1999 ) and the NHS Plan
      (DoH 2000 ) identify the importance of clinical and managerial leadership to the
      success of the government's modernisation agenda.

PMID- 27700374
TI  - AtPAP2 modulates the import of the small subunit of Rubisco into chloroplasts.
AB  - Arabidopsis thaliana purple acid phosphatase 2 (AtPAP2) is the only phosphatase
      that is dual-targeted to both chloroplasts and mitochondria. Like Toc33/34 of the
      TOC and Tom 20 of the TOM, AtPAP2 is anchored to the outer membranes of
      chloroplasts and mitochondria via a hydrophobic C-terminal motif. AtPAP2 on the
      mitochondria was previously shown to recognize the presequences of several
      nuclear-encoded mitochondrial proteins and modulate the import of pMORF3 into the
      mitochondria. Here we show that AtPAP2 binds to the small subunit of Rubisco
      (pSSU) and that chloroplast import experiments demonstrated that pSSU was
      imported less efficiently into pap2 chloroplasts than into wild-type
      chloroplasts. We propose that AtPAP2 is an outer membrane-bound phosphatase
      receptor that facilitates the import of selected proteins into chloroplasts.

PMID- 27700376
TI  - Editorial.
AB  - Observing a government in the run-up to an election is always confusing. It
      becomes difficult to distinguish between what is being said for the benefit of
      short-term gains i.e. votes, and what is part of a longer-term commitment. This
      problem can be increased by the need such governments have to complete their
      legislative framework while attempting to prepare for an election. That is why
      two recent publications are difficult to assess.

PMID- 27700377
TI  - Incident reporting goes digital.
AB  - The health and safety executive, in partnership with local authorities has
      launched a new incident reporting service to cover all employers and businesses
      in the UK.

PMID- 27700378
TI  - Trust guilty of discriminating against senior nurse.
AB  - Jane Addo, a clinical nurse manager has been awarded nearly L80,000 for racial
      discrimination.

PMID- 27700379
TI  - New jobs.
AB  - ? Kate Billingham will become assistant chief nursing officer at the Department
      of Health, responsible for developing and leading the implementation of the
      strategic action programme in public health nursing and primary care, later this
      month. Ms Billingham is currently senior research fellow in the Institute of
      General Practice and Primary Care at the University of Sheffield.

PMID- 27700380
TI  - 'The inspector calls - CHI has arrived!'

PMID- 27700381
TI  - The value of health at different ages.
AB  - This report found that respondents valued a unit of health differently depending
      on the age of the patient.

PMID- 27700382
TI  - Clinical governance facilitators gain new support association.
AB  - This month will see the launch of an organisation aimed specially at 'any
      professional whose primary responsibility is to implement and deliver clinical
      governance in any aspect of the health economy'. The organisation, the Clinical
      Governance Association will be launched in Manchester on 23 May.

PMID- 27700383
TI  - All together now.
AB  - MAKING A DIFFERENCE ( DoH 1999 ) promised a major expansion in the workforce,
      including the recruitment of 15,000 more nurses over the next three years, 6,000
      additional training places, an extensive campaign to attract nurses back into
      practice and improved workforce planning measures.

PMID- 27700385
TI  - Clinical Governance 'Unveiling the mystery - enabling the practice'.

PMID- 27700384
TI  - Spending pennies saves pounds.

PMID- 27700386
TI  - Beating the Blues.

PMID- 27700387
TI  - Quality outcomes in rehabilitation.
AB  - THIS GOVERNMENT'S time in office has seen it thinking the unthinkable and doing
      what the previous government had not dared, using nursing homes to ease pressures
      on the NHS. To those of us working in independent and voluntary homes this is an
      exciting development. Some of our colleagues working in the NHS view this with
      suspicion - the thin end of a very thick wedge. Why is the government
      contemplating using nursing homes to rehabilitate older people? What are the
      costs and benefits of using nursing homes as rehabilitation centres?

PMID- 27700388
TI  - How does the UK compare with European Standards? A review of EU healthcare
      systems using hierarchical cluster analysis.
AB  - This study is conducted to assess the validity of Tony Blair's assertion that the
      UK NHS should move towards European standards. The specific areas analysed are
      healthcare expenditure, health outcomes, health care resources and utilisation
      rates. The study examines these data for all 15 member states of the EU.

PMID- 27700389
TI  - Discussion paper 183 convergence of health care spending and health outcomes in
      the European union 1960-1995.
AB  - This reports a study examining convergence in health care expenditure and health
      outcomes of countries within the European Union.

PMID- 27700390
TI  - Taking control of information.
AB  - WHAT NURSING is and what nurses do can only be drawn from the information that
      they share in clinical communication. The information that surrounds the core of
      formal, organisational information is the informal 'professional' information of
      nursing. There is increased attention to information systems of paper and
      technology to meet accountability obligations and legal requirements. Much of the
      information attributing to the nurse's professional role is carried around 'in
      the head' with the result that nursing's professional information is either 'head
      held' or recorded on subsidiary notes. These issues give rise to challenges for
      nurse managers and leaders who could argue that the profession does need its
      informal information which should be captured within the organisation's system.

PMID- 27700391
TI  - Clinical governance in the real world.
AB  - NURSES AND midwives have a unique contribution to make to the development and
      delivery of health care and a deep commitment to realising that contribution.
      Over the years we have seen many changes and we constantly have to adapt to
      growing health care needs and expectations. The 'new NHS' represents an exciting
      but very significant challenge for the nursing and midwifery professions.

PMID- 27700392
TI  - The National Institute for Clinical Excellence.

PMID- 27700393
TI  - Recruitment and Training in Healthcare.

PMID- 27700457
TI  - Flexible working motivates all staff.
AB  - A recent survey has demolished the myth that work-life balance is only of
      interest to women with children. The survey, commissioned by Lloyds TSB on behalf
      of the Employers for Work Life Balance organisation, shows that young workers and
      men are equally interested in flexible working arrangements that allow them to
      pursue interests outside of work.

PMID- 27700458
TI  - Home closures reach crisis point.
AB  - The chief executive of the UK's sixth largest provider of residential nursing and
      specialist care has warned of further home closures unless the government
      addresses the funding issue. Craegmoor Healthcare chief executive Frank
      Richardson claims the funding crisis is now putting the government's quality
      agenda at risk.

PMID- 27700459
TI  - Editorial.
AB  - As we go to press, the whole country waits with bated breath for the announcement
      about a general election, individual nurses around the country are going through
      a living hell. Living in the countryside, it has always seemed to me that farmers
      marry nurses in disproportionate numbers. There is a natural sympathy between
      them that makes it feel right. Both have learnt to deal with the realities of
      life and death in their respective roles. They both have to make decisions that
      have a direct impact on living creatures. Most of all, neither occupation
      produces practitioners that are squeamish or naive. It seems a most appropriate
      pairing.

PMID- 27700460
TI  - Carers at the centre.
AB  - ALONGSIDE EVERY person who needs some form of care management at home there is a
      carer. The carer may be a close or distant relative, friend or neighbour. (Carers
      in this instance are those informal and unpaid people who care for an older
      person, or someone with an illness or disability).

PMID- 27700461
TI  - At the centre of research.
AB  - WHEN CLAIRE FAGIN became the Dean of the University of Pennsylvania School of
      Nursing in 1977, the school admitted 30 students to its first year class, and
      graduated the same number. It had six full-time faculty, no doctoral programme,
      no research programme and no clinical connection to the prestigious Hospital of
      the University of Pennsylvania (HUP). Its position within the university was
      precarious. Few knew of its existence or understood its mission. Students were
      often referred to as 'those dumb nurses.' Almost no one outside of nursing
      considered its scholarship scholarly or believed the discipline had anything to
      contribute to the construction of new knowledge about either health or human
      experience.

PMID- 27700462
TI  - New jobs.
AB  - ? John Bacon is the new regional director of the NHS Executive (NHSE) in London.
      He was appointed by health secretary Alan Milburn to replace Nigel Crisp, who
      recently became NHSE chief executive. Ruth Carnall has been appointed to the
      equivalent post in the south east regional office.

PMID- 27700464
TI  - Bullying and harassment.
AB  - BULLYING IS the persistent, demeaning and downgrading of human beings through
      vicious words and cruel unseen acts, which gradually undermine confidence and
      self-esteem ( Adams 1997 ). Managers faced with such allegations need to find out
      what is going on.

PMID- 27700463
TI  - The effectiveness of NVQ TRAINING.
AB  - WITH THE move of nurse education into the higher education sector in the late
      1980s, and the resultant establishment of supernumerary status for student
      nurses, nursing faced the prospect of a shortage of personnel and skills. One
      attempt to fill this gap was the introduction of the health care assistant (HCA),
      an unqualified nursing assistant who would receive work-based training, designed
      to meet the requirements of the National Council for Vocational Qualifications.

PMID- 27700465
TI  - Training needs for nurses working with children and young people.
AB  - The implications for managers in meeting the post- registration training needs of
      nurses working with children and young people are discussed by James Robinson,
      Susanne Keen, Dorothy Whyte, Sarah Baggaley and Heather Porter based on the
      results of a study conducted in Scotland in 2000.

PMID- 27700466
TI  - Information systems.
AB  - From a strategic perspective, information management has traditionally been seen
      as dominated by the technocrats; the system's design and the collection of data.
      Many would argue that we have been 'feeding the beast'!

PMID- 27700467
TI  - Zero in on violence.
AB  - THE RECOGNITION of violence in the healthcare workplace as a potential threat to
      the welfare of nurses has focused largely on the prevention of violence. However,
      it is now accepted that although violence may be reduced, it will not be
      eliminated ( Bowie 1996 ), and interest has grown in how nurses and other
      healthcare workers exposed to assault, verbal abuse or other forms of violence
      can be supported.

PMID- 27700469
TI  - Effectiveness matters.
AB  - The latest issue of Effectiveness Matters provides advice on how to access the
      best available sources of research evidence on clinical effectiveness.

PMID- 27700468
TI  - Conferences.
AB  - International Network for Psychiatric Nursing Research conference.

PMID- 27700470
TI  - Human rights act.
AB  - Learning curve publishing has produced a training resource pack on the Human
      Rights Act. The pack offers an introduction to the Act, its background, aims and
      main provisions, as well as training exercises and related materials.

PMID- 27700471
TI  - Are you an employer of the year?
AB  - Parents at Work, Lloyds TSB and the Department for Education and Employment are
      encouraging entries for their Employer of the Year award for 2001.

PMID- 27700472
TI  - Continuous quality improvement in a Maltese hospital using logical framework
      analysis.
AB  - Purpose The purpose of this paper is to present the application of logical
      framework analysis (LFA) for implementing continuous quality improvement (CQI)
      across multiple settings in a tertiary care hospital. Design/methodology/approach
      This study adopts a multiple case study approach. LFA is implemented within three
      diverse settings, namely, intensive care unit, surgical ward, and acute in
      patient psychiatric ward. First, problem trees are developed in order to
      determine the root causes of quality issues, specific to the three settings.
      Second, objective trees are formed suggesting solutions to the quality issues.
      Third, project plan template using logical framework (LOGFRAME) is created for
      each setting. Findings This study shows substantial improvement in quality across
      the three settings. LFA proved to be effective to analyse quality issues and
      suggest improvement measures objectively. Research limitations/implications This
      paper applies LFA in specific, albeit, diverse settings in one hospital. For
      validation purposes, it would be ideal to analyse in other settings within the
      same hospital, as well as in several hospitals. It also adopts a bottom-up
      approach when this can be triangulated with other sources of data. Practical
      implications LFA enables top management to obtain an integrated view of
      performance. It also provides a basis for further quantitative research on
      quality management through the identification of key performance indicators and
      facilitates the development of a business case for improvement. Originality/value
      LFA is a novel approach for the implementation of CQI programs. Although LFA has
      been used extensively for project development to source funds from development
      banks, its application in quality improvement within healthcare projects is
      scant.

PMID- 27700473
TI  - Social networks in health care teams: evidence from the United States.
AB  - Purpose The purpose of this paper is to synthesize existing evidence regarding
      health care team networks, including their formation and association with
      outcomes in various health care settings. Design/methodology/approach Network
      theory informed this review. A literature search was conducted in major databases
      for studies that used social network analysis methods to study health care teams
      in the USA between 2000 and 2014. Retrieved studies were reviewed against
      inclusion and exclusion criteria. Findings Overall, 25 studies were included in
      this review. Results demonstrated that health care team members form professional
      (e.g. consultation) and personal (e.g. friendship) networks. Network formation
      can be influenced by team member characteristics (i.e. demographics and
      professional affiliations) as well as by contextual factors (i.e. providers
      sharing patient populations and physical proximity to colleagues). These networks
      can affect team member practice such as adoption of a new medication. Network
      structures can also impact patient and organizational outcomes, including
      occurrence of adverse events and deficiencies in health care delivery. Practical
      implications Administrators and policy makers can use knowledge of health care
      networks to leverage relational structures in teams and tailor interventions that
      facilitate information exchange, promote collaboration, increase diffusion of
      evidence-based practices, and potentially improve individual and team performance
      as well as patient care and outcomes. Originality/value Most health services
      research studies have investigated health care team composition and functioning
      using traditional social science methodologies, which fail to capture relational
      structures within teams. Thus, this review is original in terms of focusing on
      dynamic relationships among team members.

PMID- 27700474
TI  - Assessing the relationship between patient satisfaction and clinical quality in
      an ambulatory setting.
AB  - Purpose The purpose of this paper is to assess the relationship between patient
      satisfaction and a variety of clinical quality measures in an ambulatory setting
      to determine if there is significant overlap between patient satisfaction and
      clinical quality or if they are separate domains of overall physician quality.
      Assessing this relationship will help to determine whether there is congruence
      between different types of clinical quality performance and patient satisfaction
      and therefore provide insight to appropriate financial structures for physicians.
      Design/methodology/approach Ordered probit regression analysis is conducted with
      overall rating of physician from patient satisfaction responses to the Clinician
      and Groups Consumer Assessment of Healthcare Providers and Systems survey as the
      dependent variable. Physician clinical quality is measured across five composite
      groups based on 26 Healthcare Effectiveness Data and Information Set (HEDIS)
      measures aggregated from patient electronic health records. Physician and patient
      demographic variables are also included in the model. Findings Better physician
      performance on HEDIS measures are correlated with increases in patient
      satisfaction for three composite measures: antibiotics, generics, and
      vaccination; it has no relationship for chronic conditions and is correlated with
      decrease in patient satisfaction for preventative measures, although the negative
      relationship for preventative measures is not robust in sensitivity analysis. In
      addition, younger physicians and male physicians have higher satisfaction scores
      even with the HEDIS quality measures in the regression. Research
      limitations/implications There are four primary limitations to this study. First,
      the data for the study come from a single hospital provider organization. Second,
      the survey response rate for the satisfaction measure is low. Third, the
      physician clinical quality measure is the percent of the physician's relevant
      patient population that met the HEDIS measure rather than if the measure was met
      for the individual patient. Finally, it is not possible to distinguish if the
      significant coefficient estimates on the physician age and gender variables are
      capturing systematic differences in physician behavior or capturing patient bias.
      Practical implications The results suggest patient satisfaction and physician
      clinical quality may be complementary, capturing similar aspects of overall
      physician quality, across some clinical quality measures but for other measures
      satisfaction and clinical quality are unrelated or negatively related. Therefore,
      for some clinical quality metrics, it will be important to separately compensate
      clinical quality and satisfaction and understand the relationship between
      metrics. Finally, the strong relationship between the level of patient
      satisfaction and physician age, physician gender, and patient age are important
      to consider when designing a physician compensation package based on patient
      satisfaction; if these differences reflect patient bias they could increase
      inequality among medical staff if compensation is based on patient satisfaction.
      Originality/value This study is the first to use physician organization data to
      examine patient satisfaction and physician performance on a variety of HEDIS
      quality metrics.

PMID- 27700476
TI  - Building a system-wide approach to community relationships with the findings of a
      scoping review in health and social care.
AB  - Purpose For leadership and management of Western health systems, good quality
      relationships are a fundamental cornerstone of organising health and social care
      (H&SC) delivery, delivering benefits across organisations and communities. The
      purpose of this paper is to explore the extant management, H&SC literature,
      grounded in older people care, reveal behaviours, processes and practices that if
      readily identified across a context will support healthy relationships across the
      "whole system" of stakeholders. Design/methodology/approach An
      academic/practitioner group designed and guided a scoping literature review of
      the H&SC and broader management literature to identify and extract important
      behaviours, processes and practices underlying the support of high-quality
      relationships. A search strategy was agreed and key health and management
      databases were interrogated and 51 papers selected for inclusion. Working with
      the practitioners, the selected papers were coded and then organised into
      emergent themes. Findings The paper outlines the relational behaviours, processes
      and practice elements that should be present within an older peoples care
      community, to support a healthy relational environment. These elements are
      presented under the five emergent literature themes of integrity, compassion,
      respect, fairness and trust. These five topics are examined in detail. A way
      forward for building statements using the review material, that may be applied to
      reveal relational patterns within older people care, is also explored and
      outlined. Research limitations/implications All literature reviews are subject to
      practical decisions around time, budget, scope and depth restraints. Therefore
      potentially relevant papers may have been missed in the review process. The
      scoping review process adapted here does not seek to make any major
      considerations with regards to the weighting of evidence behind the primary
      research. Originality/value This paper contributes to a growing need for
      designers of health systems to more fully understand, measure and draw on the
      value of relationships to help bridge the gap between diminishing resources and
      the expanding demand on H&SC services.

PMID- 27700475
TI  - Leadership and management in UK medical school curricula.
AB  - Purpose Although medical leadership and management (MLM) is increasingly being
      recognised as important to improving healthcare outcomes, little is understood
      about current training of medical students in MLM skills and behaviours in the
      UK. The paper aims to discuss these issues. Design/methodology/approach This
      qualitative study used validated structured interviews with expert faculty
      members from medical schools across the UK to ascertain MLM framework
      integration, teaching methods employed, evaluation methods and barriers to
      improvement. Findings Data were collected from 25 of the 33 UK medical schools
      (76 per cent response rate), with 23/25 reporting that MLM content is included in
      their curriculum. More medical schools assessed MLM competencies on admission
      than at any other time of the curriculum. Only 12 schools had evaluated MLM
      teaching at the time of data collection. The majority of medical schools reported
      barriers, including overfilled curricula and reluctance of staff to teach. Whilst
      88 per cent of schools planned to increase MLM content over the next two years,
      there was a lack of consensus on proposed teaching content and methods. Research
      limitations/implications There is widespread inclusion of MLM in UK medical
      schools' curricula, despite the existence of barriers. This study identified
      substantial heterogeneity in MLM teaching and assessment methods which does not
      meet students' desired modes of delivery. Examples of national undergraduate MLM
      teaching exist worldwide, and lessons can be taken from these. Originality/value
      This is the first national evaluation of MLM in undergraduate medical school
      curricula in the UK, highlighting continuing challenges with executing MLM
      content despite numerous frameworks and international examples of successful
      execution.

PMID- 27700477
TI  - Building a learning health system using clinical registers: a non-technical
      introduction.
AB  - Purpose The purpose of this paper is to describe how clinical registers were
      designed and used to serve multiple purposes in three health systems, in order to
      contribute practical experience for building learning healthcare systems.
      Design/methodology/approach Case description and comparison of the development
      and use of clinical registries, drawing on participants' experience and published
      and unpublished research. Findings Clinical registers and new software systems
      enable fact-based decisions by patients, clinicians, and managers about better
      care, as well as new and more economical research. Designing systems to present
      the data for users' daily work appears to be the key to effective use of the
      potential afforded by digital data. Research limitations/implications The case
      descriptions draw on the experience of the authors who were involved in the
      development of the registers, as well as on published and unpublished research.
      There is limited data about outcomes for patients or cost-effectiveness.
      Practical implications The cases show the significant investments which are
      needed to make effective use of clinical register data. There are limited skills
      to design and apply the digital systems to make the best use of the systems and
      to reduce their disadvantages. More use can be made of digital data for quality
      improvement, patient empowerment and support, and for research. Social
      implications Patients can use their data combined with other data to self-manage
      their chronic conditions. There are challenges in designing and using systems so
      that those with lower health and computer literacy and incomes also benefit from
      these systems, otherwise the digital revolution may increase health inequalities.
      Originality/value The paper shows three real examples of clinical registers which
      have been developed as part of their host health systems' strategies to develop
      learning healthcare systems. The paper gives a simple non-technical introduction
      and overview for clinicians, managers, policy-advisors and improvers of what is
      possible and the challenges, and highlights the need to shape the design and
      implementation of digital infrastructures in healthcare services to serve users.

PMID- 27700478
TI  - Integrating research, clinical care, and education in academic health science
      centers.
AB  - Purpose One of the major issues faced by academic health science centers (AHSCs)
      is the need for mechanisms to foster the integration of research, clinical, and
      educational activities to achieve the vision of evidence-informed decision making
      (EIDM) and optimal client care. The paper aims to discuss this issue.
      Design/methodology/approach This paper synthesizes literature on organizational
      learning and collaboration, evidence-informed organizational decision making, and
      learning-based organizations to derive insights concerning the nature of
      effective workplace learning in AHSCs. Findings An evidence-informed model of
      collaborative workplace learning is proposed to aid the alignment of research,
      clinical, and educational functions in AHSCs. The model articulates relationships
      among AHSC academic functions and sub-functions, cross-functional activities, and
      collaborative learning processes, emphasizing the importance of cross-functional
      activities in enhancing collaborative learning processes and optimizing EIDM and
      client care. Cross-functional activities involving clinicians, researchers, and
      educators are hypothesized to be a primary vehicle for integration, supported by
      a learning-oriented workplace culture. These activities are distinct from
      interprofessional teams, which are clinical in nature. Four collaborative
      learning processes are specified that are enhanced in cross-functional activities
      or teamwork: co-constructing meaning, co-learning, co-producing knowledge, and co
      using knowledge. Practical implications The model provides an aspirational vision
      and insight into the importance of cross-functional activities in enhancing
      workplace learning. The paper discusses the conceptual and empirical basis to the
      model, its contributions and limitations, and implications for AHSCs.
      Originality/value The model's potential utility for health care is discussed,
      with implications for organizational culture and the promotion of cross
      functional activities.

PMID- 27700528
TI  - The effects of consecutive night shifts and shift length on cognitive performance
      and sleepiness: a field study.
AB  - INTRODUCTION: The aim of this study was to evaluate the effects of consecutive
      night shifts (CNS) and shift length on cognitive performance and sleepiness.
      MATERIALS AND METHODS: This study evaluated the sleepiness and performance of 30
      control room operators (CROs) working in 7 nights, 7 days, 7 days off (7N7D7O)
      and 30 CROs working in 4 nights, 7 days, 3 nights, 7 days off (4N7D3N7O) shift
      patterns in a petrochemical complex on the last night shift before swinging into
      the day shift. To assess cognitive performance, the n-back test, continuous
      performance test and simple reaction time test were employed. To assess
      sleepiness, the Karolinska sleepiness scale was used. RESULTS: Both schedules
      indicated that the correct responses and response times of working memory were
      reduced (p = 0.001), while intentional errors and sleepiness increased during the
      shift work (p = 0.001). CNS had a significant impact on reaction time and
      commission errors (p = 0.001). CONCLUSION: The main duty of CROs at a
      petrochemical plant is checking hazardous processes which require appropriate
      alertness and cognitive performance. As a result, planning for appropriate
      working hours and suitable number of CNS in a rotating shift system is a
      contribution to improving CRO performance and enhancing safety.

PMID- 27700527
TI  - The P21-activated kinase PAK4 is implicated in fatty-acid potentiation of insulin
      secretion downstream of free fatty acid receptor 1.
AB  - Free fatty acid receptor 1 (FFA1/GPR40) plays a key role in the potentiation of
      glucose-stimulated insulin secretion by fatty acids in pancreatic beta cells. We
      previously demonstrated that GPR40 signaling leads to cortical actin remodeling
      and potentiates the second phase of insulin secretion. In this study, we examined
      the role of p21 activated kinase 4 (PAK4), a known regulator of cytoskeletal
      dynamics, in GPR40-dependent potentiation of insulin secretion. The fatty acid
      oleate induced PAK4 phosphorylation in human islets, in isolated mouse islets and
      in the insulin secreting cell line INS832/13. However, oleate-induced PAK4
      phosphorylation was not observed in GPR40-null mouse islets. siRNA-mediated
      knockdown of PAK4 in INS832/13 cells abrogated the potentiation of insulin
      secretion by oleate, whereas PAK7 knockdown had no effect. Our results indicate
      that PAK4 plays an important role in the potentiation of insulin secretion by
      fatty acids downstream of GPR40.

PMID- 27700529
TI  - Priority Setting and the Public Penelope Mullen Priority Setting and the Public
      and Peter Spurgeon Radcliffe 1-85775-297-X 185775297X [Formula: see text].
AB  - Written by academics at the Health Services Management Centre at the University
      of Birmingham, this book links together academic research, critical overviews of
      methods and approaches with practical applications and original research. A wide
      number of methods from a range of disciplines are described.

PMID- 27700530
TI  - Clinically Effective Purchasing - A guide for primary care organisations Norman
      Vetter Clinically Effective Purchasing - A guide for primary care organisations
      Radcliffe 1-85775-348-8 1857753488 [Formula: see text].
AB  - This book looks at the changed environment in the health services and aims to
      show how a purchaser can influence services. It deals with the background to
      purchasing services and how clinical effectiveness fits in with quality. It also
      provides practical examples and explanations.

PMID- 27700531
TI  - Involving Patients and the Public - How to do it better Ruth Chambers Involving
      Patients and the Public - How to do it better Radcliffe 1-85775-393-3 1857753933
      [Formula: see text].
AB  - A practical and clearly written book which aims to guide health professionals
      through different techniques to help them improve dialogue with patients and the
      general public. It covers areas such as using questionnaire and interview
      surveys, working in groups and gauging public opinion and sampling a population.

PMID- 27700533
TI  - Conferences.

PMID- 27700534
TI  - One year on.
AB  - WITHOUT EXCEPTION, I have been impressed by the opportunities being seized by
      nurses, midwives and health visitors. I have been in accident and emergency
      departments, where the staff have felt the winter never finished. I have been in
      hospitals which were feeling the pres- sure from waiting lists. But despite these
      pressures innovation is thriving.

PMID- 27700535
TI  - Time for change.
AB  - 'The NHS Plan means that by April 2003 all employees in the health service will
      have the right to work for an organisation that can show it has adopted flexible
      working practices.

PMID- 27700536
TI  - ?
AB  - Losing a colleague is a strange expe- rience. Most people in management have now
      gone through the process of either personally or organisation- ally seeing the
      impact of redundancy and premature retirement. Sometimes it is very sudden and
      people can feel aggrieved that they have not had the opportunity to say goodbye
      or good luck. It means that when you next meet the individual out shopping it is
      very difficult to know how to behave let alone what to say. But this social
      awkwardness does not compare to the situation when a colleague dies.

PMID- 27700537
TI  - Evolution of fungal population and mycotoxins in sorghum silage.
AB  - Silage, one of the most important feed sources for cattle, is vulnerable to
      contamination by spoilage moulds and mycotoxins because ensilage materials are
      excellent substrates for fungal growth. The aim of this study was to identify the
      mycobiota of sorghum silages, to determine the presence of aflatoxins and
      fumonisins, and to correlate these results with physical parameters of the
      silage. A total of 275 samples of sorghum were collected from dairy farms in the
      south-west region of Uruguay were silage practices are developed. The presence of
      fungi was observed in all of the sorghum samples with values varying from 0.2 *
      104 to 4085 * 104 UFC g-1. Significant difference were detected in the total
      number of fungi during the storage period; at six months there is a high risk of
      fungal spoilage. The most frequent genera isolated from sorghum samples were
      Penicillium (70%), Aspergillus (65%), Absidia (40%), Fusarium (35%), Paecilomyces
      (35%) and Alternaria, Cladosporium, Gliocadium and Mucor (30%). The toxigenic
      species most frequently found were Penicillium citrinum, Aspergillus flavus and
      Fusarium nygamai. Only two samples were contaminated by AFB1 with levels of 1 and
      14 ug kg-1. Fumonisin was detected in 40% of freshly harvest samples with levels
      ranged from 533 ug kg-1 to 933 ug kg-1. The use of silo bags seems to be an
      effective tool to store sorghum. However, the presence of toxigenic fungi show
      that regular screening for mycotoxins levels in silages must be performed to
      avoid the exposure of animals to contaminated feed and the introduction of these
      compounds into the food chain.

PMID- 27700538
TI  - Cross-Sex Hormone Treatment and Psychobiological Changes in Transsexual Persons:
      Two-Year Follow-Up Data.
AB  - CONTEXT: To date, there are few studies investigating the impact of body changes
      induced by cross-sex hormonal treatment (CHT) on psychobiological well-being in
      gender-dysphoric persons (GDs). OBJECTIVE: The objective of the study was to
      assess whether CHT-related body changes affect psychobiological well-being in
      GDs. METHODS: A consecutive series of 359 GDs was considered for a cross
      sectional section of the study. In addition, 54 GDs were studied in a 2-year
      follow-up. A physical examination was performed, including body mass index, waist
      circumference, and hair distribution. We also evaluated breast development and
      testis volume in male to female subjects and clitoris length in female to male.
      Subjects were asked to complete several psychometric measures for the assessment
      of body uneasiness, GD, and psychopathology levels. The evaluation was repeated 2
      years prospectively. RESULTS: The following results were found: 1) GDs undergoing
      CHT reported significantly lower subjective levels of GD, body uneasiness, and
      depressive symptoms as compared with those without; 2) CHT-induced body
      modifications were significantly associated with a better psychological
      adjustment; 3) during CHT, GDs reported a significant reduction of general
      psychopathology, depressive symptoms, and subjective GD, whereas social and legal
      indicators of GD showed a significant increase across time; and 4) among body
      changes induced by CHT, only breast development and increased body mass index had
      a significant impact on psychopathology reduction across time in male to female
      subjects and female to male subjects, respectively. CONCLUSIONS: The
      aforementioned results support the efficacy of CHT intervention in improving
      subjective perception of one's own body, which was partially associated with
      objective changes.

PMID- 27700539
TI  - Is a Normal TSH Synonymous With "Euthyroidism" in Levothyroxine Monotherapy?
AB  - CONTEXT: Levothyroxine (LT4) monotherapy is the standard of care for
      hypothyroidism. OBJECTIVE: To determine whether LT4 at doses that normalize the
      serum TSH is associated with normal markers of thyroid status. DESIGN: Cross
      sectional data from the US National Health and Nutrition Examination Survey (2001
      2012) was used to evaluate 52 clinical parameters. LT4 users were compared to
      healthy controls and controls matched for age, sex, race, and serum TSH.
      Regression was used to evaluate for correlation with T4 and T3 levels.
      PARTICIPANTS: A total of 9981 participants with normal serum TSH were identified;
      469 were LT4-treated. RESULTS: Participants using LT4 had higher serum total and
      free T4 and lower serum total and free T3 than healthy or matched controls. This
      translated to approximately 15-20% lower serum T3:T4 ratios in LT4 treatment, as
      has been shown in other cohorts. In comparison to matched controls, LT4-treated
      participants had higher body mass index despite report of consuming fewer
      calories/day/kg; were more likely to be taking beta-blockers, statins, and
      antidepressants; and reported lower total metabolic equivalents. A serum TSH
      level below the mean in LT4-treated participants was associated with a higher
      serum free T4 but similar free and total T3; yet those with lower serum TSH
      levels exhibited higher serum high-density lipoprotein and lower serum low
      density lipoprotein, triglycerides, and C-reactive protein. Age was negatively
      associated with serum free T3:free T4 ratio in all participants; caloric intake
      was positively associated in LT4-treated individuals. CONCLUSIONS: In a large
      population study, participants using LT4 exhibited lower serum T3:T4 ratios and
      differed in 12/52 objective and subjective measures.

PMID- 27700541
TI  - New jobs.
AB  - ? David Benton is to leave his post as chief executive of the National Board in
      Scotland, to become nursing director at Grampian University Hospitals NHS Trust.
      He will take up his new post in October.

PMID- 27700540
TI  - A SDHC Founder Mutation Causes Paragangliomas (PGLs) in the French Canadians: New
      Insights on the SDHC-Related PGL.
AB  - BACKGROUND: More than 40% of patients with paragangliomas (PGLs) harbor a
      germline mutation of the known PGL susceptibility genes, mainly in the SDHB or
      SDHD genes. OBJECTIVE: The objective of the study was to characterize the genetic
      background of the French Canadian (FC) patients with PGLs and provide new
      clinical and paraclinical insights on SDHC-related PGLs. METHODS: Genetic testing
      has been offered to FC patients affected with PGLs followed up at the adrenal
      genetics clinic at Centre hospitalier de l'Universite de Montreal. After genetic
      counseling, 29 FC patients consented for PGL genetic testing. RESULTS: Thirteen
      of 29 patients (44.8%) carried a germline mutation. The same heterozygous
      nonsense mutation at codon 133 of exon 5 of the SDHC gene (c.397C>T,
      p.[Arg133Ter]) was found in nine patients, representing 69.2% of the patients
      having a germline mutation. Seventy percent of these patients had head and neck
      PGLs. Twenty percent had multiple and 30% had malignant PGLs. We traced back the
      ascending genealogy of 10 index cases (nine patients from our cohort and one
      patient referred to us) and found that this mutation was most probably introduced
      in Nouvelle France by a couple of French settlers who established themselves in
      the 17th century. CONCLUSIONS: We found that 31% of the PGLs in the French
      Canadian can be explained by the SDHC mutation (c.397C>T, p.[Arg133Ter]). The
      dominance of the SDHC mutation is unique to the FCs and is most likely due to a
      French founder effect. SDHC gene analysis should be prioritized in FC patients
      with PGL.

PMID- 27700542
TI  - A tribute to.
AB  - BRIAN SALMON was chairman of the Lyons Catering Company and one of the first
      businessmen to display an interest in the planning and delivery of a nationalised
      health service. As well as chairing the influential committee on nursing
      management, he was also chairman of Camden and Islington Area Health Authority
      between 1974 and 1977 and a supporter of nursing in general. His sad death
      earlier this year prompts a reevaluation of the legacy of the Salmon report,
      something that is already long overdue given the re-emergence under this
      government of many of the issues that the report considered.

PMID- 27700543
TI  - Editorial.
AB  - I have never seen an angrier nurse audience in my career. It was at the RCN's
      Congress this year. The anger was not, as might be imagined, expressed over one
      of the more contentious motions for debate. It occurred in a side room off the
      main corridor of the Old Swan Hotel in Harrogate, a setting sufficiently obscure
      for Agatha Christie to have hidden there for several weeks when there was a
      national search for her! The event was a meeting of senior nurses all involved
      with care in nursing homes. These are not happy times for such nurses. The money
      available for nursing home care is being ever further constrained by central
      government and many nursing homes are closing down, as their owners can no longer
      afford to subsidise public sector healthcare provision. But this was not the
      cause of the angst.

PMID- 27700545
TI  - Scottish agency reaches out.
AB  - A Scottish nursing agency has announced plans to expand its operations, including
      four new recruitment centres in England. ScotNursing is to open eight centres in
      total, the other four in Scotland. The organisation already has one centre in
      England.

PMID- 27700544
TI  - What it means for nurses.
AB  - national IT system and database. Further guarantees of consistency and quality of
      practice will come from a new national post-qualifying award for inspectors,
      whether they have a nursing or social care background. Funding for the new
      regulatory system is intended to come from fees charged for registration and
      annual inspections.

PMID- 27700546
TI  - ?
AB  - AT THE ICN Congress in Copenhagen earlier this summer, the dominant sub-theme of
      the event was the shortage of nurses around the world. There has been some
      reporting of the emotional appeals for nurses to be allowed to return home and
      commentary on the ways in which the emigration of nurses can be turned into a
      positive experience for the individuals and the countries that they have left.
      Only one workshop addressed the confusion the profession creates in the minds of
      the public when talking about nursing and the impact that confusion has on the
      public's understanding of the role of the nurse and therefore, the reason for
      nurse shortages.

PMID- 27700547
TI  - Fall in nursing and midwifery vacancies receives cautious welcome.
AB  - Nursing and midwifery vacancies have fallen, according to figures released by the
      Department of Health earlier this summer. There has been a limited reduction in
      overall three-month vacancies in 2000-2001, down 0.5 per cent from the previous
      year, to 3.4 per cent. The figures also show that more than 3,000 nurses and
      midwives have returned to practice or were in training to do so.

PMID- 27700548
TI  - Draft proposals for replacing UKCC severely criticised.
AB  - Proposals for the new body to replace the United Kingdom Central Council for
      Nursing, Midwifery and Health Visiting (UKCC) and four national boards have been
      criticised by the Royal College of Nursing (RCN) and the Community Practitioners'
      and Health Visitors' Association (CPHVA).

PMID- 27700549
TI  - Concerns increase as nurse training for assessing older people for free care
      begins.
AB  - Training for nurses who will be assessing older people for free nursing care in
      England is expected to begin this month. Regional workshops will be held in
      preparation for the assessment scheme to go live in October. But the training
      will commence against a background of concern about the resources allocated to
      the system and level of nursing input.

PMID- 27700550
TI  - Nurses set to claim 21 per cent pay increase.
AB  - As the deadline for the Agenda for Change pay negotiations approaches, the unions
      and the Department of Health are drawing the battle lines for the next round in
      the annual pay review. It has been reported that nurses and midwives will claim
      up to a 21 per cent pay rise for 2002. The Department of Health has warned that a
      large increase would hamper the strategy to recruit more staff.

PMID- 27700551
TI  - System failure.
AB  - ROSIE DIED today and the co-operation and collaboration of well-meaning nurses
      couldn't help her. In her last few weeks of life she cried herself to sleep most
      nights. Rosie didn't cry because she was dying of cancer; she didn't cry because
      the chemotherapy and radiotherapy turned out to be ineffective. Rosie cried
      because the system failed her and those of us who knew her were, in the end,
      powerless to give her what she wanted most.

PMID- 27700552
TI  - ?
AB  - AS HEALTHCARE systems try to cope with wide-spread nursing shortages, nursing
      organisations and healthcare providers around the world are trying to recruit new
      candidates. They are beginning to consult with advertising agencies and public
      relations firms, most of whom know little or nothing about nursing.
      Unfortunately, many of these agencies tend to share stereotypical views of nurses
      who give direct care to the sick and vulnerable, and view the provision of
      traditional nursing services as dirty, menial, and disagreeable work.

PMID- 27700553
TI  - Back to basics.
AB  - PRIOR TO THE 1970s, clinical skills learned in pre-registration nurse education
      programmes were demonstrated and practised in the 'practical room'. Final
      assessments of competence consisted of student nurses being examined on their
      ability to prepare trolleys and trays to assist doctors. In the early 1970s, four
      practical-based assessments were introduced. These were conducted in the clinical
      environment by a named clinical assessor, usually the ward sister. Later,
      experiential learning was introduced whereby nursing students were expected to
      learn and develop these skills in the clinical environment, with clinical staff
      acting as teachers and assessors. As a consequence the practical room
      disappeared, along with the role of the clinical teacher.

PMID- 27700554
TI  - Monitoring ethnicity.
AB  - Accurate data on ethnic minority patients in mental health settings is scarce.
      Steve Maddern argues the case for more effective data collection to improve care
      planning and equity.

PMID- 27700555
TI  - Multiple sclerosis.
AB  - RESEARCH EVIDENCE indicates that disease-specific nurse specialists can produce
      significant benefits for patients' clinical outcomes, their quality of life and
      for the NHS budget. Various studies into the use of specialist nurses in caring
      for patients with cancer, Parkinson's disease, epilepsy and multiple sclerosis
      (MS) reported reductions in the need for urgent outpatient appointments and
      hospitalisation ( Campion 1996 , Jahanshahi et al 1994 , Walquist 1984 );
      improved rehabilitation ( Sitzia et al 1998 ) and adherence to treatment ( Mohr
      et al 1999 ); and increased patient satisfaction and well-being ( MacMahon and
      Thomas 1998 , Winters et al 1989 ).

PMID- 27700556
TI  - Social care and independent healthcare regulation will be radically reformed
      under the Care Standards Act 2000. What are the implications of this important
      piece of legislation? How will it affect the regulation of nursing agencies and
      national minimum standards relating to nursing staff in care homes? Chris Hume
      provides some answers.
AB  - FROM APRIL 2002, regulation by the 150 local authorities and 95 health
      authorities of a range of institutions and agencies will become the
      responsibility of a single national body in England, the National Care Standards
      Commission (NCSC). The Care Standards Act 2000 repeals the legislation - the
      Registered Homes Act 1984 and relevant parts of the Children's Act 1989 -
      governing local authority regulation of residential homes, private children's
      homes and nursing agencies, health authority regulation of nursing homes and
      private hospitals, and the regulation of voluntary adoption agencies and
      voluntary children's homes by the Department of Health. Similar arrangements are
      being put in place in Wales and Scotland.

PMID- 27700557
TI  - Medication-related osteonecrosis of the jaw and dental implants failures: a
      systematic review.
AB  - No well-established evidences supporting the safe use of Bisphosphonates (BPs) or
      others antiresorptive agents prior, during or after dento-alveolar surgery, are
      currently available; moreover, the real risk of osteonecrosis of the jaw (ONJ)
      development is still unknown. The aim of the present systematic review was to
      assess the scientific literature concerning the implants placement in
      antiresorptive agents-users and the related risk of implants failure and ONJ
      development. English papers published from January 2003 until December 2014 were
      identified on Medline database. Titles and abstracts retrieved form electronic
      search were screened separately by two examiners; thus, original studies dealing
      with dental implants placement during or before bone antiresorptive agents
      therapy, and the relative risk of implant failure or development of osteonecrosis
      were evaluated. Due to the heterogeneity of the included studies and the high
      risk of bias, there is no evidence of the safe use of oral antiresorptive agents
      prior or after dental implant surgery. Indeed, implant failure and ONJ
      development can occur and represent a devastating side effect that should be
      considered during the treatment. Within the limitation of the present systematic
      review, high quality studies are needed to provide an adequate level of evidence
      regarding the safety of dento-alveolar surgery during or before bone resorption
      inhibition therapy, and the increase predisposition to osteonecrosis of the jaw
      (ONJ) development. Therefore, antiresorptive agents therapy should be considered
      a risk factor until further evidence is prospectively obtained.

PMID- 27700617
TI  - A novel one-step synthesis for carbon-based nanomaterials from polyethylene
      terephthalate (PET) bottles waste.
AB  - : Nowadays our planet suffers from an accumulation of plastic products that have
      the potential to cause great harm to the environment in the form of air, water,
      and land pollution. Plastic water bottles have become a great problem in the
      environment because of the large numbers consumed throughout the world. Certain
      types of plastic bottles can be recycled but most of them are not. This paper
      describes an economical solvent-free process that converts polyethylene
      terephthalate (PET) bottles waste into carbon nanostructure materials via thermal
      dissociation in a closed system under autogenic pressure together with additives
      and/or catalyst, which can act as cluster nuclei for carbon nanostructure
      materials such as fullerenes and carbon nanotubes. This research succeeded in
      producing and controlling the microstructure of various forms of carbon
      nanoparticles from the PET waste by optimizing the preparation parameters in
      terms of time, additives, and amounts of catalyst. IMPLICATIONS: Plastic water
      bottles are becoming a growing segment of the municipal solid waste stream in the
      world; some are recycled but many are left in landfill sites. Recycling PET
      bottles waste can positively impact the environment in several ways: for
      instance, reduced waste, resource conservation, energy conservation, reduced
      greenhouse gas emissions, and decreasing the amount of pollution in air and water
      sources. The main novelty of the present work is based on the acquisition of high
      value carbon-based nanomaterials from PET waste by a simple solvent-free chemical
      technique. Thus, the prepared materials are considered to be promising, cheap,
      eco-friendly materials that may find use in different applications.

PMID- 27700618
TI  - Nanoparticles and the immune system: challenges and opportunities.

PMID- 27700619
TI  - Translating nanoparticulate-personalized cancer vaccines into clinical
      applications: case study with RNA-lipoplexes for the treatment of melanoma.
AB  - The development of nucleic acid based vaccines against cancer has gained
      considerable momentum through the advancement of modern sequencing technologies
      and on novel RNA-based synthetic drug formats, which can be readily adapted
      following identification of every patient's tumor-specific mutations.
      Furthermore, affordable and individual 'on demand' production of molecularly
      optimized vaccines should allow their application in large groups of patients.
      This has resulted in the therapeutic concept of an active personalized cancer
      vaccine, which has been brought into clinical testing. Successful trials have
      been performed by intranodal administration of sterile isotonic solutions of
      synthetic RNA vaccines. The second generation of RNA vaccines which is currently
      being developed encompasses intravenously injectable RNA nanoparticle
      formulations (lipoplexes), made up from lipid excipients, denoted RNA(LIP). A
      first product that has made its way from bench to bedside is a therapeutic
      vaccine for intravenous administration based on a fixed set of four RNA lipoplex
      drug products, each encoding for one shared tumor antigen (Lipoplex Melanoma RNA
      Immunotherapy, 'Lipo-MERIT'). This article describes the steps for translating
      these novel RNA nanomedicines into clinical trials.

PMID- 27700620
TI  - Earliest Evidence of Toxocara sp. in a 1.2-Million-Yr-Old Extinct Hyena
      (Pachycrocuta brevirostris) Coprolite from Northwest Pakistan.
AB  - The study of fossil parasites can provide insight into the antiquity of host
      parasite relationships and the origins and evolution of these paleoparasites.
      Here, a coprolite (fossilized feces) from the 1.2-million-yr-old paleontological
      site of Haro River Quarry in northwestern Pakistan was analyzed for
      paleoparasites. Micromorphological thin sectioning and Fourier-transform infrared
      spectrometry (FTIR) analysis confirms the coprolite belonged to a bone-eating
      carnivore, likely the extinct giant short-faced hyena (Pachycrocuta
      brevirostris). Parasitological analysis shows the coprolite to be positive for
      Toxocara sp. To our knowledge, this is the earliest evidence for Toxocara sp.
      found.

PMID- 27700621
TI  - Use of visual range measurements to predict fine particulate matter exposures in
      Southwest Asia and Afghanistan.
AB  - : Military personnel deployed to Southwest Asia and Afghanistan were exposed to
      high levels of ambient particulate matter (PM). However, quantitative ambient
      exposure data for conducting health studies are limited due to a lack of PM
      monitoring stations. Since visual range (VR) is proportional to particle light
      extinction, VR can serve as a surrogate for PM2.5 (particulate matter with an
      aerodynamic diameter <=2.5 um) concentrations. We used data on VR, relative
      humidity (RH), and PM2.5 ground measurements collected in Kuwait from years 2004
      2005 to establish the relationship between PM2.5 and VR. Model validation
      obtained by regressing trimester average PM2.5 predictions against PM2.5
      measurements in Kuwait produced an r2 value of 0.84. Cross validation of urban
      and rural sites in Kuwait also revealed good model fit. We applied this
      relationship to location-specific visibility data at 104 regional sites between
      years 2000-2012 to estimate monthly average PM2.5 concentrations. Monthly
      averages at sites in Iraq, Afghanistan, United Arab Emirates, Kuwait, Djibouti,
      and Qatar ranged from 10 to 365 ug/m3 during this period, while site averages
      ranged from 22 to 80 ug/m3, indicating considerable spatial and temporal
      heterogeneity in ambient PM2.5 across these regions. These data support the use
      of historical visibility data to estimate location-specific PM2.5 concentrations
      for application in epidemiological studies. IMPLICATIONS: This study demonstrates
      the ability to use airport visibility to estimate PM2.5 concentrations in
      Southwest Asian and Afghanistan. This supports the use of historical and ongoing
      visibility data to estimate PM2.5 exposure in this region of the world, where PM
      exposure information is otherwise scarce. This is of high utility to
      epidemiologists investigating the relationship between chronic exposure to PM2.5
      and respiratory diseases among deployed military personnel stationed at various
      military bases throughout the region. Such information will enable the drafting
      of improved policies relating to military health.

PMID- 27700622
TI  - Natural postharvest aflatoxin occurrence in food legumes in the smallholder
      farming sector of Zimbabwe.
AB  - Aflatoxins, mainly produced by Aspergillus flavus and Aspergillus parasiticus,
      are highly toxic and may lead to health problems such as liver cancer. Exposure
      to aflatoxins may result from ingestion of contaminated foods. Levels of AFB1,
      AFB2, AFG1 and AFG2 in samples of groundnuts (Arachis hypogaea), beans (Phaseolus
      vulgaris), cowpeas (Vigna unguiculata) and bambara nuts (Vigna subterranean)
      grown by smallholder farmers in Shamva and Makoni districts, Zimbabwe, were
      determined at harvesting, using high performance liquid chromatography after
      immunoaffinity clean-up. Aflatoxins were detected in 12.5% of groundnut samples
      with concentrations ranging up to 175.9 ug/kg. Aflatoxins were present in 4.3% of
      the cowpea samples with concentrations ranging from 1.4 to 103.4 ug/kg. Due to
      alarming levels of aflatoxins detected in legumes versus maximum permissible
      levels, there is a need to assist smallholder farmers to develop harvest control
      strategies to reduce contamination of aflatoxins in legumes.

PMID- 27700623
TI  - Evaluation of the alteration of occlusal distribution in unilateral free-end and
      intermediate missing cases.
AB  - The present study aimed to evaluate the effect of implant prostheses on the
      occlusal force and area, and the distribution of occlusal loading in unilateral
      free-end and intermediate missing cases. Fourteen healthy subjects (7 free-end
      missing cases in the first and second molars and 7 intermediate missing cases in
      the first molar region) were included. Six months after the implant prosthesis
      was placed, an occlusal evaluation was performed with or without the implant
      superstructure by using Dental PrescaleA(r) film and an occluder device. In free
      end missing cases, the total occlusal force and area, implant-side occlusal force
      and area, and implant-side occlusal force and area of the residual natural teeth
      were significantly affected by the implant prostheses. In intermediate missing
      cases, the implant-side occlusal force of the residual natural teeth was
      significantly affected by the implant prostheses. In free-end missing cases, the
      proportion of implant-side occlusal force, non-implant-side occlusal force, and
      implant-side occlusal force of the residual natural teeth relative to the total
      occlusal force was significantly affected by the implant prostheses. In the
      intermediate missing cases, the proportion of the implant-side occlusal force of
      the residual natural teeth relative to the total occlusal force was significantly
      affected by the implant prostheses. The proportion of the occlusal area was also
      significantly affected. In free-end missing cases, implant prostheses
      significantly increased the occlusal force and area, which resulted in the proper
      occlusal distribution. In intermediate missing cases, an implant prosthesis may
      only improve the same-side occlusal loading of the natural teeth.

PMID- 27700694
TI  - Assessment of spatial variation of ambient volatile organic compound levels at a
      power station in Kuwait.
AB  - : Twenty-four-hour integrated ambient air samples were collected in canisters at
      10 locations within Kuwait's major power station: Doha West Power Station to
      assess the spatial distribution of volatile organic compounds (VOCs) within the
      perimeter of the station. A total of 30 samples, i.e., three samples per
      location, were collected during February and March. The samples were analyzed
      using a gas chromatography with flame ionization detection (GC-FID) system and
      following the U.S. EPA Method TO-14A with modification. The results reflected the
      emission activities on the site and the meteorological conditions during
      sampling. Generally speaking, there was a negative correlation between the
      ambient temperature and the VOC concentrations, which indicates the sources were
      local. The halogenated compounds formed the highest proportion (i.e. 50-75 %) of
      the total VOC concentrations at the ten locations. 1,2,4-Trichlorobenzene and
      Vinyl Chloride concentrations were the highest amongst the other halogenated
      compounds. The aromatic compounds formed the least proportion (i.e. 1-4%) of the
      total VOC levels at all locations with Toluene having the highest concentrations
      amongst the aromatic compounds at seven locations. Propene, which is a major
      constituent of the fuel used, was the highest amongst the aliphatic compounds.
      The findings of this study and other relevant work suggests the measured VOC
      levels were the highest over the year, nevertheless, further work is required to
      assess the precisely temporal variation of VOC due to change in meteorological
      conditions and the emission rates. IMPLICATIONS: Assessment of VOC concentrations
      around a power plant in Kuwait during the peak season showed halogenated
      compounds to be the dominant group. The calculated indoor concentrations were
      lower than those reported in a residential area about 12 km away.

PMID- 27700693
TI  - Perspectives from health-care providers and women about completing human
      papillomavirus (HPV) self-testing at home.
AB  - Cervical cancer (CC) incidence and mortality rates are increased, and CC
      screening rates are low among Appalachian Ohio women. Mailing human
      papillomavirus (HPV) self-tests to women to complete at home is a potential new
      strategy to engage women in CC screening. The authors aimed to gain insights into
      the perceived acceptability of mailed HPV self-tests. Focus groups were conducted
      (August 2014-January 2015) among providers (physicians, nurse practitioners,
      nurses) and women in Appalachian Ohio. Providers (n = 28) and women (n = 15; age
      range: 32-62 years) reported general acceptance of HPV self-tests, however, for
      different reasons. Providers thought HPV self-testing would increase the
      proportion of under-screened women returning to the health-care system, while
      women thought self-testing would eliminate logistical and reduce psychological CC
      screening barriers. Findings provide insights into facilitators and barriers of
      completing an HPV self-test at home, returning it, reporting results, and
      providing needed follow-up care. To the authors' knowledge, no systematic
      research exists addressing providers' views regarding women's use of HPV self
      tests and the relation of such use to fostering subsequent Pap testing. This
      information will be useful in developing CC screening programs that include
      mailed HPV self-tests, as well as encouragement of follow-up Pap testing to meet
      existing CC screening guidelines.

PMID- 27700696
TI  - Enterococcus faecalis and Dental Implants.
AB  - Enterococcus faecalis appears in many tooth root infections and is not eliminated
      by root canal therapy. It can reside in tooth root canals and the surrounding
      bone. This species may vegetate in bone after extraction of an infected tooth and
      colonize a dental implant after placement in the healed site. A colonization may
      cause fixture loss or marginal bone loss. These colonizations are generally
      multibacterial and pathogenic properties can be shared via plasmids. However, E
      faecalis is not detectable with some culture techniques and thus can be missed.
      It is usually not a dominant species in these infections. Nonetheless, E faecalis
      may be a "keystone" player in dental implant bone loss or peri-implantitis. That
      is, E faecalis may be the pathogenic determinant for any particular peri
      implantitis infection of a multiple-species infection.

PMID- 27700695
TI  - The prevalence and risk factors for osteoporosis among 18- to 49-year-old Turkish
      women.
AB  - The aim of this study was to determine the prevalence of osteoporosis and
      associated risk factors in Turkish women aged 18-49 years. A population-based,
      cross-sectional study was conducted between January and April 2014. The sample (n
      = 1,792) was comprised of women aged 18-49 years, who resided in Cubuk, Ankara,
      Turkey, and were selected by simple random sampling. The data were collected in
      face-to-face interviews using an Individual Information Form and an Osteoporosis
      Risk Estimation Scale. Bone mineral density was assessed using standard dual
      energy X-ray absorptiometry. Multiple logistic regression and chi-square analyses
      were used for analyses. Most participants (80.1%) were at low risk of developing
      osteoporosis, while 6.9% were at medium to high risk of developing the disease.
      From bone mineral density levels, 33.3% were osteopenic; 4.0% were osteoporotic;
      33.3% were osteopenic at the femoral neck; and 6.7% were osteoporotic at the
      lumbar vertebra L1-L4. Further, results of multiple logistic regression analyses
      showed that osteoporosis risk was significantly associated with smoking, having
      light skin, multiparity, and having a family history of osteoporosis (p < .05).
      These results indicated that public health screening strategies for protecting
      women's bone health at earlier ages than previously thought might be beneficial.

PMID- 27700697
TI  - Body image as a target of victimization by peers/parents: Development and
      validation of the Body Image Victimization Experiences Scale.
AB  - This study developed and established the psychometric properties of the Body
      Image Victimization Experiences Scale (BIVES). The BIVES retrospectively assesses
      the frequency (Part A-frequency) and effect (Part B-impact) of victimization
      experiences pertaining to body image, perpetrated by peers and parents/caregivers
      in childhood and adolescence. Distinct samples of Portuguese women were recruited
      in 2013-2014: two nonclinical samples of the general population (n = 1,177), aged
      18-60 years, and a clinical sample of patients with Binge Eating Disorder (BED; n
      = 73), aged 19-59 years. An exploratory factor analysis was conducted in 632
      participants. A confirmatory factor analysis (CFA) and the scale's psychometric
      properties were tested in 545 participants. The ability of the BIVES to
      discriminate the clinical from a nonclinical sample was examined. The scale
      presented two factors indicating the sources of the victimization-peers and
      parents. CFA results confirmed the scale's structure. The BIVES presented very
      good internal consistency, construct and discriminant validity, good test-retest
      reliability, and was associated with related constructs, body image shame, and
      eating psychopathology. The scale adequately discriminated between the clinical
      sample and a nonclinical sample. The BIVES is a valid and reliable measure that
      allows for a comprehensive assessment of body image-related victimization
      experiences.

PMID- 27700698
TI  - Dance practice and well-being correlates in young women.
AB  - Clinical research has shown the mental health benefits of dance practice. This
      has become a significant subject of inquiry in psychotherapeutic settings for the
      elderly and adolescents. However, the relationship between dance practice and
      correlates of psychological well-being, such as mindfulness and life satisfaction
      (LS)-two relevant indicators of mental health, has been explored relatively
      little in young women. The present study contrasted mindfulness and LS in young
      women (n = 81) who practiced dance regularly in three modern dance schools in the
      Province of Barcelona with a control group of non-practitioners (n = 120)
      studying at a university in Barcelona. The data were collected during the first
      semester of 2015, and the total sample had an average age of 20.88 +/- 3.36
      years. Analyses of covariance showed higher levels of both mindfulness and LS in
      the dance practitioners, while a multiple regression analysis showed that, after
      controlling for age, dance was the factor most strongly associated with LS,
      explaining 28% of the variance in LS. These results are discussed in terms of the
      embodiment theory, and conclusions suggest that dance may be an effective gender
      focused practice to enhance well-being and promote mental health in young women.

PMID- 27700804
TI  - Out of body, out of mind? An examination of out-of-body experiences and
      dissociative disorders.

PMID- 27700755
TI  - Golgi-to-plastid trafficking of proteins through secretory pathway: Insights into
      vesicle-mediated import toward the plastids.
AB  - The diversity of protein targeting pathways to plastids and their regulation in
      response to developmental and metabolic status is a key issue in the regulation
      of cellular function in plants. The general import pathways that target proteins
      into and across the plastid envelope with changes in gene expression are critical
      for plant development by regulating the response to physiological and metabolic
      changes within the cell. Glycoprotein targeting to complex plastids involves
      routing through the secretory pathway, among others. However, the mechanisms of
      trafficking via this system remain poorly understood. The present article
      discusses our results in site-specific N-glycosylation of nucleotide
      pyrophosphatase/phosphodiesterases (NPPs) glycoproteins and highlights protein
      delivery in Golgi/plastid pathway via the secretory pathway. Furthermore, we
      outline the hypotheses that explain the mechanism for importing vesicles
      trafficking with nucleus-encoded proteins into plastids.

PMID- 27700861
TI  - Enhancing women's health: A call for social work research.
AB  - This article presents a critical synthesis of the social work empirical
      literature on women's health. In light of recent policy changes that directly
      affect women's health and social work, the authors conducted a literature review
      of recent publications (2010-2015) regarding social work and women's health
      nationally. Despite frequent accounts cited in the literature, there has been no
      comprehensive review of issues involving women's health and social work in the
      United States. The purpose of this review is to examine the current social work
      literature addressing women's health at the national (U.S.) level. This research
      presents a summary description of the status of the social work literature
      dealing with women's health, specifically 51 articles published between 2010 and
      2015. Our search highlights the need for social work research to fill gaps and
      more fully address the needs of women across the lifespan.

PMID- 27700906
TI  - Moving women's health forward: Mainstreaming gender into global women's health
      programming.

PMID- 27700907
TI  - Weighty issues.

PMID- 27700862
TI  - Life is Precious: A Community-Based Program to Reduce Suicidal Behavior in Latina
      Adolescents.
AB  - Latina adolescents have high rates of suicidal behavior. Life is Precious (LIP),
      a community-based program in New York City, helps adolescents and families
      address risk factors facing Latinas. Participants are assessed for suicidal
      ideation, depressive and other psychiatric symptoms, and family functioning, at
      program entry and every 4 months during participation. Demographic
      characteristics and suicide attempts are also tracked. In the study period, there
      were no attempted or completed suicides in this high-risk population. Suicidal
      ideation, depressive symptoms, anger, and posttraumatic stress symptoms decreased
      significantly during participation. The LIP model shows promise for helping to
      address suicidal risk factors facing Latinas. However, in the absence of a
      comparison group, participants' improvement may be due to their engagement in
      mental health treatment more generally, or to the passage of time, rather than
      specifically to LIP. Nevertheless, as very little is known about how to address
      risk factors unique to Latina adolescents, these early findings may be of
      interest to the community serving Latina adolescents and the lessons may be of
      interest to programs serving adolescents from other racial/ethnic groups. Future
      research should develop comparison groups and test LIP implementation in other
      settings.

PMID- 27700908
TI  - A qualitative study of work-life balance amongst specialist orthodontists in the
      United Kingdom.
AB  - OBJECTIVE: To identify factors affecting work-life balance amongst male and
      female orthodontists in the UK. DESIGN: A qualitative interview-based study with
      a cross-sectional design. SUBJECTS: Specialist orthodontists working in
      specialist practice and the hospital service in the UK were selected by purposive
      sampling. METHODS: In-depth semi-structured interviews were conducted with 18
      orthodontic specialists. Interview transcripts were analyzed using Framework
      Analysis. RESULTS: Four main themes pertaining to work-life balance in
      orthodontics were identified: work factors affecting work-life balance, life
      factors affecting work-life balance, perception and effects of work-life balance
      and suggestions for managing work-life balance within the profession.
      CONCLUSIONS: There was substantial variation in the work-life balance of the
      orthodontists interviewed in this study; however the majority reported high
      levels of career satisfaction despite difficulties maintaining a good work-life
      balance. Whilst there were some clear distinctions in the factors affecting work
      life balance between the hospital environment and specialist practice (including
      additional professional commitments and teaching/training-related issues), there
      were also a number of similarities. These included, the lack of flexibility in
      the working day, managing patient expectations, taking time off work at short
      notice and the ability to work part-time.

PMID- 27700909
TI  - Knowing your face: A componential analysis of self-perceived facial
      attractiveness.
AB  - Facial attractiveness (FA) is a highly agreed upon and socially important
      characteristic, but contemporary research has not fully investigated individuals'
      enhancement of their FA. We used the social relations model (SRM) to analyze data
      from 187 participants. In face-to-face groups of four, participants rated their
      own and others' FA. We assessed the degree of FA enhancement using unconfounded
      measures of both self-insight and social comparison. Results indicated African
      Americans and men enhanced more than Caucasians and women. Race effects were
      mediated by psychological adjustment, while gender effects were related to meta
      perceptions. Men tended to view themselves through a "frog prince" lens, such
      that they accurately predicted others' lesser views of them but persisted in
      overly positive self-perceptions of FA. Findings suggest further consideration of
      SRM measures, meta-perceptions, and a focus on sample diversity in the study of
      self-enhancement.

PMID- 27700910
TI  - Exploring Homophobia in Tbilisi, Georgia.
AB  - The purpose of this study is to determine statistical predictors of homophobic
      attitudes among the residents of Tbilisi, Georgia. We analyze 2013 survey data
      from a representative sample of the Tbilisi adult population. Residents were
      asked about their attitudes, beliefs, and political and social values in the
      context of the May 17, 2013 attack on LGBT activists on the International Day
      Against Homophobia and Transphobia (IDAHOT). Findings show that homophobia is
      significantly predicted by male gender, lower levels of education, acceptance of
      social inequality, nonliberal attitudes, and perceiving homosexuals as a "threat
      to national security." However, psychological perceptions and personal
      experiences also indirectly influence homophobic attitudes: the findings suggest
      that males report homophobic attitudes more often than females do and tend to be
      even more homophobic when they believe that homosexuality is inborn rather than
      acquired. The study also found that people without liberal attitudes tend to be
      more homophobic when they have personal contacts with homosexuals. This article
      highlights the need for a more comprehensive approach to education and the
      promotion of liberal values as well as legal equality for LGBTQ individuals to
      decrease the level of homophobia in Georgian society and, specifically, in
      Tbilisi.

PMID- 27700963
TI  - Build Your Own Pension: Framing Pension Reform and Choice in Newspapers.
AB  - Recent pension reforms in Norway mean that old-age pensions to a greater extent
      are a function of adaptations made and decisions made throughout the lifetime.
      How much you work, who you work for, when you retire, and how you invest will
      influence your standard of living as an old-age pensioner. This article
      investigates one important source of information about retirement and pension,
      namely service journalism in main national newspapers. How is the issue of
      pension framed in these articles? And what kind of advice is presented by which
      kind of actors? Findings indicate that service journalism is dominated by pension
      industry sources, and old-age pension is framed as a function of individual
      investment choices rather than as citizens' rights.

PMID- 27700964
TI  - Continued Declines in Teen Births in the United States, 2015.
AB  - KEY FINDINGS: *The teen birth rate declined to another historic low for the
      United States in 2015, down 8% from 2014 to 22.3 births per 1,000 females aged 15
      19. *The birth rates for teenagers aged 15-17 and 18-19 declined in 2015 to 9.9
      and 40.7, respectively, which are record lows for both groups. *In 2015, birth
      rates declined to 6.9 for Asian or Pacific Islander, 16.0 for non-Hispanic white,
      25.7 for American Indian or Alaska Native, 31.8 for non-Hispanic black, and 34.9
      for Hispanic female teenagers aged 15-19. *Birth rates fell to record lows for
      nearly all race and Hispanic-origin groups of females aged 15-19, 15-17, and 18
      19 in 2015. The birth rate for teenagers aged 15-19 has fallen almost
      continuously since 1991, reaching historic lows for the nation every year since
      2009 (1-4). Despite declines in all racial and ethnic groups, teen birth rates
      continue to vary considerably by race and ethnicity. Moreover, the U.S. teen
      birth rate remains higher than in other industrialized countries (5).
      Childbearing by teenagers continues to be a matter of public concern. This report
      presents the recent and long-term trends and disparity in teen childbearing by
      race and Hispanic origin.

PMID- 27700965
TI  - Editorial.

PMID- 27700966
TI  - Epidemiology of Fracture in Adults from Ontario, Canada, with Chronic Kidney
      Disease: An Examination of Fracture Burden Using Administrative Health Data.
AB  - Fractures are associated with morbidity and mortality. Individuals with chronic
      kidney disease (CKD) experience bone mineral metabolism changes, which increases
      fracture risk. Researchers have quantified the epidemiology of fractures in
      adults with CKD using administrative health databases from Ontario, Canada, held
      at the Institute for Clinical Evaluative Sciences. Results demonstrated that many
      individuals with non-transplant CKD sustain fractures, with the risk increasing
      as kidney function declines. However, fracture risk in kidney transplant
      recipients was lower than previously described, which suggests recipients may not
      be a high-risk fracture group. There is a need to test fracture prevention
      interventions in the CKD population.

PMID- 27700968
TI  - The Challenge Before Us.

PMID- 27700967
TI  - Care for Patients with Complex Needs: Canadian Results from the Commonwealth Fund
      2015 International Health Policy Survey of Primary Care Physicians.
AB  - Good primary care is essential for the effective management of patients with
      chronic conditions in the community and to ensure their care is well coordinated
      with other parts of the system. The Commonwealth Fund 2015 International Health
      Policy Survey compares the views and experiences of primary care physicians in 11
      countries including Canada. The survey found nearly all (98%) primary care
      doctors across countries treat patients with complex needs in their practice.
      However, when examining questions on chronic disease management and coordination
      of care with other providers, Canadian results are mixed compared to the
      international average, and show variation at the provincial level. Opportunities
      likely exist to learn from other countries that have a more systematic approach
      to primary care delivery.

PMID- 27700969
TI  - What Gets in the Way of Person-Centred Care for People with Multimorbidity?
      Lessons from Ontario, Canada.
AB  - Person-centred care is becoming a key component of quality in health systems
      worldwide. Although the term can mean different things, it typically entails
      paying attention to the needs and background of health system users, involving
      them in decisions that affect their health, assessing their care goals and
      implementing a coordinated plan of care that aligns with their unique
      circumstances. The importance of practising a person-centred approach in care
      delivery dominates policy and research rhetoric worldwide, yet competing goals
      set by policy planners to save money, eliminate waste and sustain the healthcare
      system challenge the implementation of such an approach. In this commentary, we
      begin by exploring the concept of person-centred care and its importance among
      people who frequently use healthcare, such as those with multimorbidity. We then
      provide a brief overview of the evolution of Ontario's healthcare system and its
      emphasis on achieving cost savings. In doing so, we illustrate the implications
      for health system users, particularly people with multimorbidity, their carers
      and formal care providers. Finally, we reflect on examples of innovations that
      are striving to deliver person-centred care, despite a constrained healthcare
      environment. While a step in the right direction, we conclude that these "one
      off" strategies are unsustainable in the absence of supporting policy levers.

PMID- 27700970
TI  - Understanding Clinical Complexity the Hard Way: A Primary Care Journey.
AB  - Ten years ago, complexity was not a term often used in primary care. In the last
      decade, however, the population seen in primary care has shifted, posing
      substantial challenges for both primary care providers and health systems. In
      this essay, I will document the approaches that evolved in an academic family
      practice environment to address the challenges posed by complex patients typified
      by multiple concurrent chronic conditions and social determinants challenges. I
      will describe the research that lead to the creation, implementation and
      evaluation of an inter-professional model of care and associated outcomes. I will
      describe how this work subsequently led to the evolution of clinical models and
      research projects designed to reframe the discourse around complexity as well as
      move forward on elaborating new policy, clinical and service delivery
      innovations. I will conclude with some thoughts about what I see as the major
      challenges in the short and immediate term for research and practice, drawing on
      15 years of practice and research experience with complex populations.

PMID- 27700971
TI  - eHealth Advances in Support of People with Complex Care Needs: Case Examples from
      Canada, Scotland and the US.
AB  - Information technology (IT) in healthcare, also referred to as eHealth
      technologies, may offer a promising solution to the provision of better care and
      support for people who have multiple conditions and complex care needs, and their
      caregivers. eHealth technologies can include electronic medical records,
      telemonitoring systems and web-based portals, and mobile health (mHealth)
      technologies that enable information sharing between providers, patients, clients
      and their families. IT often acts as an enabler of improved care delivery, rather
      than being an intervention per se. But how are different countries seeking to
      leverage adoption of these technologies to support people who have chronic
      conditions and complex care needs? This article presents three case examples from
      Ontario (Canada), Scotland and Kaiser Permanente Colorado (United States) to
      identify how these jurisdictions are currently using technology to address
      multimorbidity. A SWOT (strengths, weaknesses, opportunities, threats) analysis
      is presented for each case and a final discussion addresses the future of eHealth
      for complex care needs. The case reports presented in this manuscript mark the
      foundational work of the Multi-National eHealth Research Partnership Supporting
      Complex Chronic Disease and Disability (the eCCDD Network); a CIHR-funded project
      intended to support the international development and uptake of eHealth tools for
      people with complex care needs.

PMID- 27700972
TI  - Applying Clinical Practice Guidelines to the Complex Patient: Insights for
      Practice and Policy from Stroke Rehabilitation.
AB  - In Canada, policy makers are working to align services with the Stroke
      Rehabilitation Best Practice Recommendations (SRBPR). Complicating the
      application of clinical practice guidelines (CPGs) is the fact that most strokes
      occur in the context of other diagnoses. We sought to understand clinicians' use
      of the CPGs and ascertain how much guidance regarding multimorbidity was
      available in the SRBPR. Study results indicated that using the recommendations
      was problematic due to a perceived lack of guidance regarding comorbidities and
      multimorbidity, and concerns regarding the applicability to "real-life patients."
      Comorbidities were mentioned in less than half of the recommendations, but no
      explicit guidance was provided regarding the management of comorbidities. Given
      the prevalence of multimorbidity in stroke rehabilitation, this clinical context
      is ideal for development and testing of CPGs that account for multimorbidity and
      other complexity factors. Results may also suggest limitations to using CPGs in
      the development of activity-based funding models.

PMID- 27700973
TI  - Performance Measurement for People with Multimorbidity and Complex Health Needs.
AB  - This paper reviews approaches to performance measurement in health systems with
      particular attention to people with multimorbidity and complex health needs.
      Performance measurement should be informative and used by multiple stakeholders
      in order to align performance improvement efforts. System performance measures
      must allow for macro-system and meso-organization and provider-level reporting,
      and they should be relevant and important to stakeholders at each level, as well
      as to patients and all potential care recipients. Measures that assess health
      outcomes and individuals' experiences with providers, including care planning and
      coordination of care across providers, are essential to assess value for people
      with multimorbidity and complex health needs. I suggest that performance
      measurement for this population should be motivated by the Complexity Framework
      and organized by the Triple Aim. Based on the care needs and appropriate goals
      for the health system for this population, applicable measures and suggestions
      for implementing and using performance measurement systems are identified.
      Particularly in the case of people with multimorbidity and complex health needs,
      performance measures must move beyond measures specific to individual encounters
      to track care for people over time and space. Measures must be rooted in
      individuals' own needs and goals for care. New systems are required to enable
      collection and reporting of these measures.

PMID- 27700974
TI  - Realizing the Potential of Rehabilitative Care for People with Complex Health
      Conditions: The Time Is Now.
AB  - In today's demographic landscape, with its aging population and increasing number
      of individuals who are living with multiple chronic conditions and comorbidities,
      the healthcare system is tasked with responding to the needs of medically complex
      individuals. However, the pressures arising from this emerging demographic are
      felt not only within the acute care sector at the point of medical crisis but
      along the entire continuum of the healthcare system. Rehabilitative care plays a
      key role in that continuum by providing the process through which individuals are
      engaged in interventions to address their functional (both cognitive and
      physical) and psychosocial care goals to help them carry on with the business of
      living.

PMID- 27700975
TI  - It Takes Two to Tango: Researchers and Decision-Makers Collaborating to Implement
      Practice Changes for Patients with Multimorbidity.
AB  - An integrated knowledge translation strategy is a key factor in fostering the
      implementation of practice changes. Building on a 15-year history of projects
      that include close collaboration between researchers and decision-makers in the
      Saguenay region of Quebec (Canada), the authors identify several key elements
      that resulted in practice changes in primary care and improved outcomes for
      patients with multimorbidity.

PMID- 27700976
TI  - Building Bridges to Integrate Care (BRIDGES): Incubating Health Service
      Innovation across the Continuum of Care for Patients with Multiple Chronic
      Conditions.
AB  - Integrating care for people with complex needs is challenging. Indeed, evidence
      of solutions is mixed, and therefore, well-designed, shared evaluation approaches
      are needed to create cumulative learning. The Toronto-based Building Bridges to
      Integrate Care (BRIDGES) collaborative provided resources to refine and test nine
      new models linking primary, hospital and community care. It used mixed methods, a
      cross-project meta-evaluation and shared outcome measures. Given the range of
      skills required to develop effective interventions, a novel incubator was used to
      test and spread opportunities for system integration that included operational
      expertise and support for evaluation and process improvement.

PMID- 27700977
TI  - A "Simple" Evidence-Based Intervention to Improve Care Transitions for Frail
      Patients with Complex Health Conditions: Why Didn't It Work as Expected?
AB  - The transition from hospital to home is a vulnerable period for patients with
      complex conditions, who are often frail, at risk for adverse events and unable to
      navigate a system of poorly coordinated care in the post-discharge period. Care
      transition interventions are seen as effective care coordinating mechanisms for
      reducing avoidable adverse events associated with the transition of the patient
      from the hospital to the home. A study was undertaken to evaluate the
      effectiveness of a care transition intervention involving a hand-off between a
      hospital-based care transitions nurse and a community-based rapid response nurse.
      Two focus groups were held, one involving rapid response nurses and the other
      involving care transition nurses. Individual interviews were conducted with the
      managers (n = 2) and executives (n = 2) to identify the factors that facilitated
      or were barriers to its implementation. Using thematic content analysis, it was
      found that the effectiveness of transitional coordination efforts was thwarted by
      ineffective communication, which affected the quality of the underlying
      relationships between the two teams. Other barriers to achieving the desired
      outcomes included the following: issues of role clarity, role awareness and
      acceptance, the adequacy and reinforcement of coordinating mechanisms, the
      effectiveness of the information exchange protocols and the absence of shared
      measures of accountability. Clinical integration initiatives have fewer human
      resource and financial implementation barriers compared with organizational
      integration efforts but are complex undertakings requiring clear alignment
      between organizations, shared accountability measures, effective communication
      processes and relationships of trust and respect between interprofessional teams.

PMID- 27700978
TI  - Improving Outcomes through Transformational Health and Social Care Integration -
      The Scottish Experience.
AB  - The Scottish Parliament recently passed legislation on integrating healthcare and
      social care to improve the quality and outcomes of care and support for people
      with multiple and complex needs across Scotland. This ambitious legislation
      provides a national framework to accelerate progress in person-centred and
      integrated care and support for the growing number of people who have multiple
      physical and mental health conditions and complex needs. Additional investment
      and improvement capacity is helping to commission support and services that are
      designed and delivered with people in local communities and in partnership with
      housing, community, voluntary and independent sectors.

PMID- 27700979
TI  - In Conversation with Nick Goodwin.

PMID- 27700980
TI  - CEO Perspective: A Health System for Patients with Complex Conditions:
      Reflections from Bridgepoint's Transformation.

PMID- 27700981
TI  - Circulating anti-Mullerian hormone concentrations in relation to age and season
      in male and female beluga (Delphinapterus leucas).
AB  - The present study aimed to describe serum anti-Mullerian hormone (AMH) patterns
      of ex situ male and female beluga to examine the influence of age (divided into 5
      year categories) or sexual maturation and reproductive season. In males aged 5-9
      years, AMH concentrations were significantly (P<0.05) higher than those in all
      age categories exceeding 15 years and were not influenced by season (P=0.57). AMH
      concentrations in females peaked in the 5-9-year age category during the breeding
      season and decreased (P<0.05) after 9 years of age. Aged females displayed lower
      (P<0.05) AMH concentrations than immature and mature animals and immature females
      secreted higher concentrations than mature animals (P=0.03). For mature females,
      seasonal differences (P=0.02) in AMH concentrations were detected, with females
      in the breeding season displaying higher AMH concentrations than in the non
      breeding season. This is the first time AMH has been characterised in a cetacean
      species and the first potential hormonal evidence of reproductive senescence in
      beluga. Further research is required to determine if this hormone can be used as
      a predictor of fertility for the species.

PMID- 27700982
TI  - A combination of insulin-like growth factor I (IGF-I) and FSH promotes
      proliferation of prepubertal bovine Sertoli cells isolated and cultured in vitro.
AB  - Beef and dairy bull calves fed a low-nutrition diet during early life had
      decreased concentrations of circulating insulin-like growth factor I (IGF-I),
      delayed increases in testosterone, smaller testes and delayed puberty compared
      with those fed high-nutrition diets. Although IGF-1 has important roles in
      Sertoli cell function in rats and mice, this has not been well documented in
      bulls. The objectives of this study were to: (1) isolate Sertoli cells from bull
      calves at 8 weeks of age, (2) culture them in vitro and (3) determine the effects
      of IGF-I, FSH and a combination of both hormones on cell proliferation. For
      Sertoli cell isolation, minced testicular tissues were treated with collagenase
      followed by trypsin and hyaluronidase to digest seminiferous tubules and release
      Sertoli cells. In this study, Sertoli cells were successfully isolated from 8
      week-old Holstein bull calves (n=4) and these cells were cultured for up to 8
      days. A combination of IGF-I and FSH increased proliferation (~18%) and therefore
      cell number (1.5-fold) of prepubertal bovine Sertoli cells in culture, providing
      clear evidence that IGF-I has a similar role in bovine Sertoli cells as reported
      in rodents.

PMID- 27700983
TI  - Non-surgical sterilisation methods may offer a sustainable solution to feral
      horse (Equus caballus) overpopulation.
AB  - Feral horses are a significant pest species in many parts of the world,
      contributing to land erosion, weed dispersal and the loss of native flora and
      fauna. There is an urgent need to modify feral horse management strategies to
      achieve public acceptance and long-term population control. One way to achieve
      this is by using non-surgical methods of sterilisation, which are suitable in the
      context of this mobile and long-lived species. In this review we consider the
      benefits of implementing novel mechanisms designed to elicit a state of permanent
      sterility (including redox cycling to generate oxidative stress in the gonad,
      random peptide phage display to target non-renewable germ cells and the
      generation of autoantibodies against proteins essential for conception via
      covalent modification) compared with that of traditional immunocontraceptive
      approaches. The need for a better understanding of mare folliculogenesis and
      conception factors, including maternal recognition of pregnancy, is also reviewed
      because they hold considerable potential in providing a non-surgical mechanism
      for sterilisation. In conclusion, the authors contend that non-surgical measures
      that are single shot and irreversible may provide a sustainable and effective
      strategy for feral horse control.

PMID- 27700984
TI  - An electrostatic selection mechanism controls sequential kinase signaling
      downstream of the T cell receptor.
AB  - The sequence of events that initiates T cell signaling is dictated by the
      specificities and order of activation of the tyrosine kinases that signal
      downstream of the T cell receptor. Using a platform that combines exhaustive
      point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting,
      and deep sequencing, we have defined the specificities of the first two kinases
      in this pathway, Lck and ZAP-70, for the T cell receptor zeta chain and the
      scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by
      utilizing an electrostatic mechanism that excludes substrates with positively
      charged residues and favors LAT and SLP-76 phosphosites that are surrounded by
      negatively-charged residues. This mechanism prevents ZAP-70 from phosphorylating
      its own activation loop, thereby enforcing its strict dependence on Lck for
      activation. The sequence features in ZAP-70, LAT, and SLP-76 that underlie
      electrostatic selectivity likely contribute to the specific response of T cells
      to foreign antigens.

PMID- 27700987
TI  - A novel method for the quantitation of gingerol glucuronides in human plasma or
      urine based on stable isotope dilution assays.
AB  - The bio-active compounds of ginger (Zingiber officinale Roscoe), the gingerols,
      are gaining considerable attention due to their numerous beneficial health
      effects. In order to elucidate the physiological relevance of the ascribed
      effects their bioavailability has to be determined taking their metabolization
      into account. To quantitate in vivo generated [6]-, [8]- and [10]-gingerol
      glucuronides in human plasma and urine after ginger tea consumption, a
      simultaneous and direct liquid chromatography-tandem mass spectrometry method
      based on stable isotope dilution assays was established and validated. The
      respective references as well as the isotopically labeled substances were
      synthesized and characterized by mass spectrometry and NMR. Selective isolation
      of gingerol glucuronides from human plasma and urine by a mixed-phase anion
      exchange SPE method led to recovery rates between 80.8 and 98.2%. LC-MS/MS
      analyses in selected reaction monitoring modus enabled a highly sensitive
      quantitation of gingerol glucuronides with LoQs between 3.9-9.8nmol/L in plasma
      and 39.3-161.1nmol/L in urine. The method precision in plasma and urine varied in
      the range+/-15%, whereas the intra-day accuracy in plasma and urine showed values
      between 78 and 122%. The developed method was then applied to a pilot study in
      which two volunteers consumed one liter ginger tea. Pharmacokinetic parameters
      like the maximum concentration (cmax), the time to reach cmax (tmax), area under
      the curve (AUC), elimination rate constant (kel) and elimination half-life (t1/2)
      were calculated from the concentration-time curve of each gingerol glucuronide.
      The obtained results will enable more detailed investigation of gingerol
      glucuronides as bioactives in their physiologically relevant concentrations.

PMID- 27700985
TI  - Stochasticity in the miR-9/Hes1 oscillatory network can account for clonal
      heterogeneity in the timing of differentiation.
AB  - Recent studies suggest that cells make stochastic choices with respect to
      differentiation or division. However, the molecular mechanism underlying such
      stochasticity is unknown. We previously proposed that the timing of vertebrate
      neuronal differentiation is regulated by molecular oscillations of a
      transcriptional repressor, HES1, tuned by a post-transcriptional repressor, miR
      9. Here, we computationally model the effects of intrinsic noise on the Hes1/miR
      9 oscillator as a consequence of low molecular numbers of interacting species,
      determined experimentally. We report that increased stochasticity spreads the
      timing of differentiation in a population, such that initially equivalent cells
      differentiate over a period of time. Surprisingly, inherent stochasticity also
      increases the robustness of the progenitor state and lessens the impact of
      unequal, random distribution of molecules at cell division on the temporal spread
      of differentiation at the population level. This advantageous use of biological
      noise contrasts with the view that noise needs to be counteracted.

PMID- 27700986
TI  - Rac1-mediated membrane raft localization of PI3K/p110beta is required for its
      activation by GPCRs or PTEN loss.
AB  - We aimed to understand how spatial compartmentalization in the plasma membrane
      might contribute to the functions of the ubiquitous class IA phosphoinositide 3
      kinase (PI3K) isoforms, p110alpha and p110beta. We found that p110beta localizes
      to membrane rafts in a Rac1-dependent manner. This localization potentiates Akt
      activation by G-protein-coupled receptors (GPCRs). Thus genetic targeting of a
      Rac1 binding-deficient allele of p110beta to rafts alleviated the requirement for
      p110beta-Rac1 association for GPCR signaling, cell growth and migration. In
      contrast, p110alpha, which does not play a physiological role in GPCR signaling,
      is found to reside in nonraft regions of the plasma membrane. Raft targeting of
      p110alpha allowed its EGFR-mediated activation by GPCRs. Notably, p110beta
      dependent, PTEN null tumor cells critically rely upon raft-associated PI3K
      activity. Collectively, our findings provide a mechanistic account of how
      membrane raft localization regulates differential activation of distinct PI3K
      isoforms and offer insight into why PTEN-deficient cancers depend on p110beta.

PMID- 27700988
TI  - Preparative separation of cacao bean procyanidins by high-speed counter-current
      chromatography.
AB  - In this work, an efficient method for preparative separation of procyanidins from
      raw cacao bean extract by high-speed counter-current chromatography (HSCCC) was
      developed. Under the optimized solvent system of n-hexane-ethyl acetate-water
      (1:50:50, v/v/v) with a combination of head-tail and tail-head elution modes,
      various procyanidins fractions with different polymerization degrees were
      successfully separated. UPLC, QTOF-MS and 1H NMR analysis verified that these
      fractions contained monomer up to pentamer respectively. Dimeric procyanidin B2
      (purity>86%) could be isolated by HSCCC in a single run. Other individual
      procyanidins in these fractions could be further isolated and purified by
      preparative HPLC. The developed HSCCC together with preparative HPLC techniques
      appeared to be a useful tool for large preparation of different procyanidins from
      cacao beans. Furthermore, by antioxidant activity assays, it was proved that both
      fractions and individual procyanidins possessed greater antioxidant activities
      compared to standard trolox. The antioxidant activities of procyanidins increase
      as the increase of their polymerization degree.

PMID- 27700989
TI  - Strategy of mitigating ammonium-rich waste inhibition on anaerobic digestion by
      using illuminated bio-zeolite fixed-bed process.
AB  - Intermittent illumination combined with bio-zeolite fixed-bed process was
      utilized to improve the efficiency of anaerobic digestion with ammonium-rich
      substrate. The batch experiments were carried out at NH4+-N concentration of
      2211mg/L under intermittent illumination and dark (as control) conditions,
      respectively. The illuminated bioreactor achieved higher methane production
      (287mL/g-DOC) and ATP value (0.38MUmol/L) than that under dark condition. Then
      the bio-zeolite fixed-bed bioreactor (NH4+-N concentration: 3000mg/L) was used to
      study the additional efficiency on the illuminated ammonium-rich anaerobic
      digestion process. The result showed that the illuminated fixed-bed bioreactor
      presented the greatest methane concentration (70%), methane yield (283mL/g-DOC)
      and quantity of methanogens comparing with no-bed bioreactor. Furthermore, the
      illuminated fixed-bed bioreactor achieved better performance during 118-day semi
      continuous fermentation. The combination of the intermittent illumination and bio
      zeolite fixed-bed strategy contributed to the higher efficiency and stability of
      the ammonium-rich anaerobic digestion process.

PMID- 27700991
TI  - Impact of mixing time and energy on the dispersion effectiveness and droplets
      size of oil.
AB  - The effects of mixing time and energy on Alaska Northern Slope (ANS) and diluted
      bitumen Cold Lake Blend (CLB) were investigated using EPA baffled flask test.
      Dispersion effectiveness and droplet size distribution were measured after 5-120
      min. A modeling method to predict the mean droplet size was introduced for the
      first time to tentatively elucidate the droplet size breakup mechanism. The ANS
      dispersion effectiveness greatly increased with dispersant and mixing energy.
      However, little CLB dispersion was noted at small energy input (epsilon = 0.02
      Watt/kg). With dispersant, the ANS droplet size distribution reached quasi
      equilibrium within 10 min, but that of CLB seems to reach quasi-equilibrium after
      120 min. Dispersants are assumed ineffective on high viscosity oils because
      dispersants do not penetrate them. We provide an alternative explanation based on
      the elongation time of the droplets and its residence in high intensity zones.
      When mixing energy is small, CLB did not disperse after 120 min, long enough to
      allow the surfactant penetration. Our findings suggest that dispersants may
      disperse high viscosity oils at a rougher sea state and a longer time. The latter
      could determine how far offshore one can intervene for effective responses to a
      high viscosity oil spill offshore.

PMID- 27700990
TI  - Sustained sensing as an emerging principle in second messenger signaling systems.
AB  - Bacteria utilize a diverse set of nucleotide second messengers to regulate
      cellular responses by binding macromolecular receptors (RNAs and proteins).
      Recent studies on cyclic di-GMP (c-di-GMP) have shown that this signaling
      molecule binds multiple receptors to regulate different steps in the same
      biological process. We propose this property of the same molecule regulating
      multiple steps in the same process is biologically meaningful and have termed
      this phenomenon 'sustained sensing'. Here, we discuss the recent findings that
      support the concept of sustained sensing of c-di-GMP levels and provide
      additional examples that support the utilization of sustained sensing by other
      second messengers. Sustained sensing may be widespread in bacteria and provides
      an additional level of complexity in prokaryotic signal transduction networks.

PMID- 27700992
TI  - Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic
      sub-lethal exposure.
AB  - Sodium fluoride (NaF), one of the most frequently used fluoride compound is
      composed of Na+ and F-. Apart from its use in water fluoridation, NaF also acts
      as a major component for different dental products like toothpastes, gels and
      mouth rinses etc. The present study was carried out to explore the toxic impact
      of chronic NaF exposure on a non-target organism, Drosophila melanogaster. The
      larvae exposed to different concentrations of NaF through food showed a
      significant increase in HSP70 expression both qualitatively and quantitatively.
      The altered tail length and tail intensity in Comet assay validate the increased
      DNA damage in treated larvae. The activity of AChE, oxidative stress marker
      enzymes, phase I and phase II detoxifying enzymes were found to be significantly
      inhibited in the treated larvae when compared to control though there was no
      evidence of dose dependent change in each case. The alterations in the mentioned
      parameters can be due to increased body Fluoride ion (F-) concentration since the
      analysis with ion electrode analyzer revealed that F- concentration increased
      significantly with NaF treatment. Hence, the results suggest that D. melanogaster
      manifest prominent toxic response when subjected to chronic exposure to sub
      lethal NaF concentrations.

PMID- 27700993
TI  - Comparative study for the removal and destruction of pentachlorophenol using
      activated magnesium treatment systems.
AB  - Chlorophenols are highly toxic, environmentally-persistent compounds which have
      been classified as probable human carcinogens by the United States Environmental
      Protection Agency. Due to the high toxicity of these compounds, it is necessary
      to treat water and soils with concentrations of chlorophenols above the detection
      limit set by regulatory agencies. The aim of this work is to demonstrate the
      capabilities of using ball-milled magnesium for the dechlorination of PCP.
      Comparison of dechlorination processes were performed in an attempt to determine
      the most effective system for degradation of PCP to phenol. Three systems with
      powerful capabilities of treatment were studied: ball-milled zero-valent
      magnesium (ZVMg), ball-milled zero-valent magnesium carbon (ZVMg/C), and ball
      milled zero-valent magnesium with palladium (ZVMg/Pd). In addition to measuring
      PCP disappearance, all byproducts were identified and quantified for each
      degradation system. The results of these studies indicate that all three of the
      systems degrade PCP within 30 min. The most rapid and complete PCP dechlorination
      is achieved using ball-milled Mg/Pd and a matrix consisting of at least 0.02 g
      Mg0/mL ethanol, and 10 MUL acetic acid/mL ethanol, in which case 20 ng/MUL of PCP
      was dechlorinated to chlorophenols in approximately 15 min with complete
      dechlorination achieved in six days. Carbon mass balances of 90.16% for Mg,
      94.76% (Mg/C) and 97.05% (Mg/Pd) verify dechlorination was responsible for
      declining concentrations of PCP. The reactions of PCP degradation and phenol
      formation were found to follow pseudo-first order kinetics for all systems.
      Further work will consist of optimization and development of field-scale
      applications.

PMID- 27700994
TI  - Efficient destruction of hexachlorobenzene by calcium carbide through
      mechanochemical reaction in a planetary ball mill.
AB  - Mechanochemical destruction (MCD) is a good alternative to traditional
      incineration for the destruction of persistent organic pollutants (POPs), like
      hexachlorobenzene (HCB), and the key is to find an efficient co-milling reagent.
      Toward this aim, HCB was milled with various reagents in a planetary ball mill at
      room temperature, and CaC2 was found to be the best one. HCB can be destroyed
      completely within 20 min at a mass ratio of CaC2/HCB = 0.9 and a rotation speed
      of 300 rpm. The ground samples were characterized by X-ray diffraction, X-ray
      photoelectron spectroscopy and Fourier transform infrared spectroscopy. The
      results show that the destruction products are nonhazardous CaCl2 and carbon
      material with both crystalline and amorphous structures. On these bases, possible
      reaction pathways were proposed. Considering its excellent efficiency and safety,
      CaC2 may be the most feasible co-milling regent for MCD treatment of HCB.
      Further, the results are instructive for the destruction of other POPs.

PMID- 27700995
TI  - Adsorption of organophosphorus pesticides in tropical soils: The case of karst
      landscape of northwestern Yucatan.
AB  - This article discusses the adsorption of four organophosphorus pesticides
      diazinon, dimethoate, methyl parathion, and sulfotep-in soil samples from four
      sites-Komchen, Xcanatun, Chablekal and Mococha- in the northwest of Yucatan,
      Mexico. These pesticides have been detected in groundwater at concentrations
      greater than 5 (MUg/L) during recent monitoring campaigns in the study area. In
      this region, groundwater contamination is exacerbated by its karst aquifer, which
      is susceptible to contamination and is considered very vulnerable. The
      experimental work was carried out using the batch equilibrium technique.
      Pesticide analyses by solid-phase extraction and gas chromatography were
      performed. The equilibrium adsorption data were analyzed by Henry, Langmuir and
      Freundlich models. The results indicate that the Freundlich model provides the
      best correlation of the experimental data. Freundlich adsorption coefficients Kf
      were in the range of 1.62-2.35 for sulfotep, 2.43 to 3.25 for dimethoate, from
      5.54 to 9.27 for methyl parathion, and 3.22 to 5.17 for diazinon. Freundlich
      adsorption coefficients were normalized to the content of organic carbon in the
      soil to estimate the sorption coefficient of organic carbon (KOC). KOC values
      were in the range of 9.45-71.80, indicated that four pesticides have low
      adsorption on the four studied soils, which represents a high risk of
      contamination to the aquifer.

PMID- 27700997
TI  - Characterization of pH-fractionated humic acids derived from Chinese weathered
      coal.
AB  - To reduce the compositional and structural heterogeneity of humic acids (HAs) and
      achieve better use of HA resources, in this study, we report a new sequential
      dissolution method for HAs derived from Chinese weathered coal. This method was
      used to separate HAs into seven fractions by adjusting the pH (3-10) of the
      extraction solution. The results showed that the HA fractions derived from
      Chinese weathered coal were concentrated up to 90.31% in the lower pH solutions
      (3-7). The compositional and structural characteristics of the HA fractions were
      determined by elemental analysis; ultraviolet-visible (UV-Vis), Fourier transform
      infrared (FTIR), and solid-state 13C-nuclear magnetic resonance (NMR)
      spectroscopies; and other techniques. The results showed significant differences
      among the HA fractions. The concentrations of the total acidic groups and the
      carboxyl groups decreased with the increasing pH of the extraction solution.
      However, the HA fractions derived from extraction solutions with pH 3-4 had
      relatively lower aromaticity but a higher protonated carbon content. The HA
      fractions derived from extraction solutions with pH 6-7 had the highest
      aromaticity and the greatest abundance of COO/N-C=O. This study demonstrated that
      adjusting the pH of the extraction solution is one way to fractionate HAs from
      Chinese weathered coal and to obtain HA fractions with compositions and
      structures that could serve as useful material for study and utilization.

PMID- 27700996
TI  - Pilot investigation of two-stage biofiltration for removal of natural organic
      matter in drinking water treatment.
AB  - A pilot study employing two parallel trains of two-stage biofiltration, i.e., a
      sand/anthracite (SA) biofilter followed by a biologically-active granular
      activated carbon (GAC) contactor, was conducted to test the efficiency,
      feasibility and stability of biofiltration for removing natural organic matter
      (NOM) after coagulation in a drinking water treatment plant. Results showed the
      biofiltration process could effectively remove turbidity (<0.1 NTU in all
      effluents) and NOM (>24% of dissolved organic carbon (DOC), >57% of UV254, and
      >44% of SUVA254), where the SA biofilters showed a strong capacity for turbidity
      removal, while the GAC contactors played the dominant role in NOM removal. The
      vertical profile of water quality in the GAC contactors indicated the middle
      upper portion was the critical zone for the removal of NOM, where relatively
      higher adsorption and enhanced biological removal were afforded. Fluorescence
      excitation-emission matrix (EEM) analysis of NOM showed that the GAC contactors
      effectively decreased the content of humic-like component, while protein-like
      component was refractory for the biofiltration process. Nutrients (NH4-N and PO4
      P) supplementation applied upstream of one of the two-stage biofiltration trains
      (called engineered biofiltration) stimulated the growth of microorganisms, and
      showed a modest effect on promoting the biological removal of small non-aromatic
      compositions in NOM. Redundancy analysis (RDA) indicated influent UV254 was the
      most explanatory water quality parameter for GAC contactors' treatment
      performance, and a high load of UV254 would result in significantly reduced
      removals of UV254 and SUVA254.

PMID- 27700998
TI  - Coagulation-flocculation as pre-treatment for micro-scale Fe/Cu/O3 process (CF
      mFe/Cu/O3) treatment of the coating wastewater from automobile manufacturing.
AB  - A coagulation-flocculation as pre-treatment combined with mFe/Cu/O3 (CF
      mFe/Cu/O3) process was developed to degrade the pollutants in automobile coating
      wastewater (ACW). In coagulation-flocculation (CF) process, high turbidity
      removal efficiency (97.1%) and low COD removal efficiency (10.5%) were obtained
      under the optimal conditions using Al2(SO4)3.18H2O and CaO. The effluent of CF
      process (ECF) was further disposed by mFe/Cu/O3 process, and its key operating
      parameters were optimized by batch experiments. Optimally, COD removal efficiency
      of ECF obtained by the mFe/Cu/O3 process (i.e., 87.6% after 30 min treatment) was
      much higher than those of mFe/Cu alone (8.3%), ozone alone (46.6%), and
      mFe/Cu/air (6.1%), which confirms the superiority of the mFe/Cu/O3 process. In
      addition, the analysis results of UV-vis, excitation-emission matrix (EEM)
      fluorescence spectra and GC/MS further confirm that the phenol pollutants of ECF
      had been effectively decomposed or transformed after CF-mFe/Cu/O3 process
      treatment. Meanwhile, B/C ratio of ACW increased from 0.19 to 0.56, which
      suggests the biodegradability was improved significantly. Finally, the operating
      cost of CF-mFe/Cu/O3 process was about 1.83 USD t-1 for ACW treatment. Therefore,
      the combined process is a promising treatment technology for the coating
      wastewater from automobile manufacturing.

PMID- 27701000
TI  - Effect of halide ions on the photodegradation of ibuprofen in aqueous
      environments.
AB  - Typically contained within ambient surface waters and certain industrial
      wastewaters, are plentiful halide ions, which possess varying degrees of
      photosensitivity. The effects of halide ions on the photodegradation of ibuprofen
      (IBP) were investigated under UV irradiation using a 500 W mercury lamp as a
      light source. Studies of the mechanism of halide ions were inclusive of both
      their light shielding effects and quenching experiments. The results indicated
      that chloride ion has a slight inhibition against IBP photodegradation under
      neutral condition, and significant inhibition is observed with bromide ions and
      iodide ions. In addition to the observed increased rate of IBP photodegradation
      in conjunction with elevated pH in solution, the inhibitory effect of halide ions
      was different. When the pH value of the IBP solution was 5, chloride ions were
      seen to facilitate the photodegradation of IBP. Halide ions can inhibit IBP
      photodegradation by means of a light attenuation effect. All of the halide ions
      significantly facilitated the generation of 1O2.

PMID- 27700999
TI  - Chemical composition and direct electrochemical oxidation of table olive
      processing wastewater using high oxidation power anodes.
AB  - Table olive processing wastewater (TOW) is a notoriously polluting due to its
      high organic and phenol content. To reduce them, an electrochemical process has
      been studied for the treatment of this effluent. Experiments were performed with
      a cell equipped with lead dioxide (PbO2) or boron-doped diamond (BDD) as anode
      and platinum as cathode, where Table Olive Wastewater (TOW) were destroyed by
      hydroxyl radicals formed at the anode surface from water oxidation. The
      comparative study of both systems shows the performance of the BDD anode compared
      to PbO2, explained by the large amounts of hydroxyl radicals generated effective
      at BDD anode and its synthesis characteristics. Using LC/MS analysis, it was
      possible to determine hydroxytyrosol, as major phenolic compounds, in table olive
      processing wastewater and its concentration reach 890 mg L-1. A possible reaction
      mechanism oxidation for hydroxytyrosol was proposed. The kinetics decays for
      hydroxytyrosol degradation on PbO2 anode follows a pseudo-first order reaction
      with a rate constant 0.9 h-1 for japp value 20 mA cm-2.

PMID- 27701001
TI  - A case report of laparoscopic cholecystectomy in situs inversus totalis:
      Technique and anatomical variation.
AB  - BACHGROUND: Since the first laparoscopic cholecystectomy report in situs inversus
      totalis in 1991, the safety of this procedure has still been questionable. A few
      surgeons were preferred to perform an open cholecystectomy due to technical
      difficulties as well as various anatomical varieties that can be faced during
      surgery. CASE PRESENTATION: We report a case report of a 50 years old patient
      came with epigastric pain that radiated to her left shoulder, intermittent
      nausea, vomiting and bloating after some meals. She did not associate her
      symptoms with fatty food. She was a known case of situs inversus totalis and had
      a previous laparoscopic Nissen fundoplication that we performed 5 years ago. A
      laparoscopic cholecystectomy was performed by a left-handed surgeon, illustrating
      challenges, technique, and the advantages of left-handed surgeon over right
      handed ones. DISCUSSION: After the first discovery of situs inversus totalis by
      Fabricus in the 1600 the standard procedure for cholelithiasis was open surgery.
      The introduction of the first laparoscopic cholecystectomy in patients with situs
      inversus put surgeons in challenge for performing laparoscopic rather than open
      surgery for patients with situs inversus diagnosed with gallbladder disease. Only
      67 cases used laparoscopic cholecystectomy in treating situs inversus patients
      with cholelithiasis. Although technical difficulties and expected anatomical
      variation are the main challenges in those patients, the current literature
      confirms the safety of laparoscopy in such cases. CONCLUSION: Despite having all
      these difficulties, handling this type of operations can be safe and uneventful
      especially with experienced surgeon.

PMID- 27701003
TI  - Aorto-hepatic bypass graft for repair of an inferior pancreatico-duodenal artery
      aneurysm associated with coeliac axis occlusion: A case report.
AB  - INTRODUCTION: Inferior pancreatico-duodenal artery (IPDA) aneurysms are very rare
      and commonly associated with coeliac axis stenosis or occlusion due to
      atherosclerosis, thrombosis or median arcuate ligament syndrome. We present a
      case of a surgical repair of an IPDA aneurysm with the use of a supra-coeliac
      aorto-hepatic bypass with a polytetrafluoroethylene (PTFE) graft, following a
      failed initial attempt at an endovascular repair. PRESENTATION: A 75 year old
      female, who was under investigation for night sweats, was referred to our team
      with an incidental finding of a 19mm fusiform IPDA aneurysm. Initial attempt at
      endovascular coiling of the aneurysm was unsuccessful. Elective surgical repair
      involved excision of the aneurysm and to restore arterial inflow to the hepatic
      artery, a PTFE bypass graft was used from the supra-coeliac aorta to the hepatic
      artery. The patient was well 2 months following the procedure with a patent graft
      shown on contrast enhanced computer tomography (ceCT). DISCUSSION: Management
      options for IPDA aneurysms include radiologically guided endovascular approach or
      surgical repair. Given the high mortality of greater than 50% with ruptured
      aneurysms intervention is indicated in all detected cases. CONCLUSION: Surgical
      excision with bypass grafting from the supra-coeliac aorta, as reported by our
      team, represents a satisfactory management option in patients where
      interventional approaches have failed or are not appropriate.

PMID- 27701002
TI  - A rare clinic entity: Huge trichobezoar.
AB  - INTRODUCTION: Trichobezoar is a rare clinical entity in which a ball of hair
      amasses within the alimentary tract. It can either be found as isolated mass in
      the stomach or may extend into the intestine. Trichobezoars mostly occur in young
      females with psychiatric disorders such as trichophagia and trichotillomania.
      CASE REPORT: Authors present a giant trichobezoar in an 18year old female
      presented with complaints of upper abdominal mass, epigastric area pain, anorexia
      and weight loss. The patient underwent trans-abdominal ultrasonography (USG),
      Computed tomography (CT), upper gastrointestinal endoscopy and subsequently
      laparotomy. USG was inconclusive due to non-specific findings. It revealed a
      thick echogenic layer with posterior dirty shadowing extending from the left sub
      diaphragmatic area to the right sub hepatic region obscuring the adjacent
      structures. Abdominal CT images revealed a huge, well defined, multi-layered,
      heterogeneous, solid appearing, non-enhancing mass lesion in the gastric lumen
      extending from the gastric fundus to the pyloric canal. An endoscopic attempt was
      performed for removal of this intraluminal mass, but due to its large size, and
      hard nature, the endoscopic removal was unsuccessful. Finally the large
      trichobezoar was removed with open laparotomy. CONCLUSION: Trichobezoars should
      be suspected in young females with long standing upper abdominal masses; as the
      possibility of malignancy is not very common in this age group. While USG is
      inconclusive, trichobezoar can be accurately diagnosed with CT. In patient with
      huge trichobezoar, laparotomy can be performed firstly because of big size and
      location of mass, and psychiatric recommendation should be made to prevent
      relapse of this entity.

PMID- 27701004
TI  - Cervical fracture from chronic steroid usage presenting as a stroke: A case
      report.
AB  - INTRODUCTION: Misdiagnosis of Brown-Sequard-like presentations can delay
      treatment; potentially endangering the positive outcomes a patient might
      otherwise have had. Stroke mimics can be perceived as signaling the end of urgent
      investigation and care once stroke is ruled out; however, stroke mimics
      themselves can require prompt care. Herein, we discuss an extremely rare case
      where stroke was ruled out, resulting in a lapse in care that lead to an
      exacerbated hemiparesis over the following week. PRESENTATION OF CASE: We present
      a patient with an occult cervical spine fracture with extension of the neck,
      caused by reduced bone density from a chronic steroid regimen. Nine days after
      the initial onset of her neurological symptoms, the patient presented to the ED
      with the complaint of left sided weakness and right-sided sensory loss. She was
      determined to have a left- sided Brown Sequard syndrome, which resolved following
      anterior cervical discectomy and fusion at C4-C6 and a laminectomy from C4-C6.
      DISCUSSION: This case indicated that patients with dangerously low bone density
      should be weaned off chronic steroid therapy to prevent the onset of osteoporotic
      symptoms early in adulthood. Furthermore, this case emphasizes the importance of
      continued investigation of symptoms if a stroke is ruled out and the need for
      more diligent monitoring of bone density of chronic steroid users. CONCLUSION:
      Stroke mimics can require the same urgency in care and diagnosis as strokes
      themselves.

PMID- 27701005
TI  - Pulmonary venous aneurysm: Forming a glove balloon-like shape.
AB  - INTRODUCTION: Pulmonary venous aneurysm (PVA) is a candidate for surgery because
      of the risk of rupture and continued growth even if the patient does not develop
      mitral valve disorders. PRESENTATION OF CASE: We report the case of PVA that
      continued to increase in size throughout a 17-year observational period.
      DISCUSSION AND CONCLUSION: The location and form of the aneurysm are important to
      consider when choosing the surgical approach. If the aneurysm forms a "glove
      balloon-like shape," lobectomy is necessary because end-to-end anastomosis is
      difficult to perform in such cases.

PMID- 27701006
TI  - Incorporation of feedback during beat synchronization is an index of neural
      maturation and reading skills.
AB  - Speech communication involves integration and coordination of sensory perception
      and motor production, requiring precise temporal coupling. Beat synchronization,
      the coordination of movement with a pacing sound, can be used as an index of this
      sensorimotor timing. We assessed adolescents' synchronization and capacity to
      correct asynchronies when given online visual feedback. Variability of
      synchronization while receiving feedback predicted phonological memory and
      reading sub-skills, as well as maturation of cortical auditory processing; less
      variable synchronization during the presence of feedback tracked with maturation
      of cortical processing of sound onsets and resting gamma activity. We suggest the
      ability to incorporate feedback during synchronization is an index of
      intentional, multimodal timing-based integration in the maturing adolescent
      brain. Precision of temporal coding across modalities is important for speech
      processing and literacy skills that rely on dynamic interactions with sound.
      Synchronization employing feedback may prove useful as a remedial strategy for
      individuals who struggle with timing-based language learning impairments.

PMID- 27701008
TI  - Global production, use, and emission volumes of short-chain chlorinated paraffins
      - A minimum scenario.
AB  - Short-chain chlorinated paraffins (SCCPs) show high persistence, bioaccumulation
      potential, and toxicity (PBT properties). Consequently, restrictions on
      production and use have been enforced in several countries/regions. The Stockholm
      Convention on Persistent Organic Pollutants recognized the PBT properties and
      long-range transport potential of SCCPs in 2015 and is now evaluating a possible
      global phase-out or restrictions. In this context, it is relevant to know which
      countries are producing/using SCCPs and in which amounts, and which applications
      contribute most to their environmental emissions. To provide a first
      comprehensive overview, we review and integrate all publicly available data on
      the global production and use of both chlorinated paraffins (CPs) as a whole and
      specifically SCCPs. Considerable amount of data on production/use of CPs and
      SCCPs are missing. Based on the available data and reported emission factors, we
      estimate the past and current worldwide SCCP emissions from individual
      applications. Using the available data as a minimum scenario, we conclude: (i)
      SCCP production and use is increasing, with the current worldwide production
      volume being 165,000t/year at least, whereas the global production of total CPs
      exceeds 1milliont/year. (ii) The worldwide release of SCCPs from their production
      and use to air, surface water, and soil between 1935 and 2012 has been in the
      range of 1690-41,400t, 1660-105,000t, and 9460-81,000t, respectively. (iii) The
      SCCP manufacture and use in PVC, the use in metal working applications and
      sealants/adhesives, and the use in plastics and rubber contribute most to the
      emissions to air, surface water, and soil. Thus, the decrease in the
      environmental emissions of SCCPs requires reduction of SCCP use in (almost) all
      applications. (iv) Emissions due to the disposal of waste SCCPs cannot be
      accurately estimated, because relevant information is missing. Instead, we
      conduct a scenario analysis to provide some insights into it.

PMID- 27701007
TI  - Time is ripe: maturation of metabolomics in chronobiology.
AB  - Sleep and circadian rhythms studies have recently benefited from metabolomics
      analyses, uncovering new connections between chronobiology and metabolism. From
      untargeted mass spectrometry to quantitative nuclear magnetic resonance
      spectroscopy, a diversity of analytical approaches has been applied for biomarker
      discovery in the field. In this review we consider advances in the application of
      metabolomics technologies which have uncovered significant effects of sleep and
      circadian cycles on several metabolites, namely phosphatidylcholine species,
      medium-chain carnitines, and aromatic amino acids. Study design and data
      processing measures essential for detecting rhythmicity in metabolomics data are
      also discussed. Future developments in these technologies are anticipated vis-a
      vis validating early findings, given metabolomics has only recently entered the
      ring with other systems biology assessments in chronometabolism studies.

PMID- 27701009
TI  - Cannabis and its effects on driving skills.
AB  - Traffic policies show growing concerns about driving under the influence of
      cannabis, since cannabinoids are one of the most frequently encountered
      psychoactive substances in the blood of drivers who are drug-impaired and/or
      involved in accidents, and in the context of a legalization of medical marijuana
      and of recreational use. The neurobiological mechanisms underlying the effects of
      cannabis on safe driving remain poorly understood. In order to better understand
      its acute and long-term effects on psychomotor functions involved in the short
      term ability and long-term fitness to drive, experimental research has been
      conducted based on laboratory, simulator or on-road studies, as well as on
      structural and functional brain imaging. Results presented in this review show a
      cannabis-induced impairment of actual driving performance by increasing lane
      weaving and mean distance headway to the preceding vehicle. Acute and long-term
      dose-dependent impairments of specific cognitive functions and psychomotor
      abilities were also noted, extending beyond a few weeks after the cessation of
      use. Some discrepancies found between these studies could be explained by factors
      such as history of cannabis use, routes of administration, dose ranges, or study
      designs (e.g. treatment blinding). Moreover, use of both alcohol and cannabis has
      been shown to lead to greater odds of making an error than use of either alcohol
      or cannabis alone. Although the correlation between blood or oral fluid
      concentrations and psychoactive effects of THC needs a better understanding,
      blood sampling has been shown to be the most effective way to evaluate the level
      of impairment of drivers under the influence of cannabis. The blood tests have
      also shown to be useful to highlight a chronic use of cannabis that suggests an
      addiction and therefore a long-term unfitness to drive. Besides blood, hair and
      repeated urine analyses are useful to confirm abstinence.

PMID- 27701010
TI  - The development of the grasp height effect as a measure of efficient action
      planning in children.
AB  - One effect that illustrates how people adjust aspects of their grasping according
      to situational constraints is the grasp height effect; when reaching for objects
      positioned at different heights, adults' grasp height (vertical position of the
      hand on the object) tends to correlate negatively with object height. This
      indicates that grasp positions are planned so that they facilitate later
      placements of the object. The current study investigated the development of the
      grasp height effect with 3-year-old children, 5-year-old children, and adults.
      This paradigm allows for studying efficient action planning in the context of a
      simple task with relatively low motor requirements. Other tasks used so far for
      studying this issue involved relatively complex adjustments of hand position that
      younger children might have found difficult to perform. Usually, preschoolers'
      performance on these tasks was relatively low. We expected that, due to the lower
      motor requirements of the grasp height paradigm, clearer evidence of efficient
      planning might be found in preschool children. A second focus of this study was
      to explore children's behavior in different movement phases of the grasping task.
      Whereas the task of placing an object at different heights involves planning,
      putting the object back to its original position seems to depend on recall. The
      results indicate a significant grasp height effect in all age groups but also
      significant development across the studied age range. Regarding the second
      movement phase, when participants were required to put the objects back on the
      original home shelf, 3- and 5-year-olds did not seem to act based on recall in
      this context.

PMID- 27701011
TI  - Further evidence for a role of the ADRB2 gene in risk for posttraumatic stress
      disorder.
AB  - The aim of the present study was to attempt to replicate the recently reported
      finding associating rs2400707 of the Adrenoceptor Beta 2, Surface (ADRB2) gene
      and childhood trauma on PTSD symptoms. Participants included a predominantly
      veteran cohort of non-Hispanic blacks (NHB; n = 949) and a pre-dominantly veteran
      cohort of non-Hispanic whites (NHW; n = 759). No main effects were observed for
      rs2400707 on PTSD diagnosis. Among the NHB participants, we observed an
      interaction between rs2400707 and history of childhood trauma, whereby with each
      additional A allele, the odds of having PTSD increased by 1.31, but only among
      those who had experienced childhood trauma (p = 0.038). The interaction with
      rs2400707 and childhood trauma was not observed among the NHW study participants
      (p = 0.892). Taken together, the findings from the present research provide
      further evidence that the adrenergic system may be an important modulator of PTSD
      risk; however, additional work is still needed to clarify the exact nature of the
      relationship between PTSD and rs2400707 of the ADRB2 gene.

PMID- 27701013
TI  - Peer-based health interventions for people with serious mental illness: A
      systematic literature review.
AB  - Health interventions delivered by peer specialists or co-facilitated by peer
      specialists and health professionals can help improve the physical health of
      people with serious mental illness (SMI). Yet, the quality of the studies
      examining these health interventions and their impact on health outcomes remains
      unclear. To address this gap, we conducted a systematic literature review of peer
      based health interventions for people with SMI. We rated the methodological
      quality of studies, summarized intervention strategies and health outcomes, and
      evaluated the inclusion of racial and ethnic minorities in these studies. We used
      the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines
      to conduct our systematic literature review. Electronic bibliographic databases
      and manual searches were used to locate articles that were published in English
      in peer-reviewed journals between 1990 and 2015, described peer-based health
      interventions for people with SMI, and evaluated the impact of the interventions
      on physical health outcomes. Two independent reviewers used a standardized
      instrument to rate studies' methodological quality, abstracted study
      characteristics, and evaluated the effects of the interventions on different
      health outcomes. Eighteen articles were reviewed. Findings indicated that the
      strength of the evidence generated from these studies is limited due to several
      methodological limitations. Mixed and limited intervention effects were reported
      for most health outcomes. The most promising interventions were self-management
      and peer-navigator interventions. Efforts to strengthen the evidence of peer
      based interventions require a research agenda that focuses on establishing the
      efficacy and effectiveness of these interventions across different populations
      and settings.

PMID- 27701012
TI  - A systematic review and secondary data analysis of the interactions between the
      serotonin transporter 5-HTTLPR polymorphism and environmental and psychological
      factors in eating disorders.
AB  - OBJECTIVES: To summarize and synthesize the growing gene x environment (GxE)
      research investigating the promoter region of the serotonin transporter gene (5
      HTTLPR) in the eating disorders (ED) field, and overcome the common limitation of
      low sample size, by undertaking a systematic review followed by a secondary data
      meta-analysis of studies identified by the review. METHOD: A systematic review of
      articles using PsycINFO, PubMed, and EMBASE was undertaken to identify studies
      investigating the interaction between 5-HTTLPR and an environmental or
      psychological factor, with an ED-related outcome variable. Seven studies were
      identified by the systematic review, with complete data sets of five community (n
      = 1750, 64.5% female) and two clinical (n = 426, 100% female) samples combined to
      perform four secondary-data analyses: 5-HTTLPR x Traumatic Life Events to predict
      ED status (n = 909), 5-HTTLPR x Sexual and Physical Abuse to predict bulimic
      symptoms (n = 1097), 5-HTTLPR x Depression to predict bulimic symptoms (n =
      1256), and 5-HTTLPR x Impulsiveness to predict disordered eating (n = 1149).
      RESULTS: Under a multiplicative model, the low function (s) allele of 5-HTTLPR
      interacted with traumatic life events and experiencing both sexual and physical
      abuse (but not only one) to predict increased likelihood of an ED and bulimic
      symptoms, respectively. However, under an additive model there was also an
      interaction between sexual and physical abuse considered independently and 5
      HTTLPR, and no interaction with traumatic life events. No other GxE interactions
      were significant. CONCLUSION: Early promising results should be followed-up with
      continued cross-institutional collaboration in order to achieve the large sample
      sizes necessary for genetic research.

PMID- 27701014
TI  - MicroED opens a new era for biological structure determination.
AB  - In 2013 we unveiled the cryo-electron microscopy (CryoEM) method of MicroED, or
      three-dimensional (3D) electron diffraction of microscopic crystals. Here tiny 3D
      crystals of biological material are used in an electron microscope for
      diffraction data collection under cryogenic conditions. The data is indexed,
      integrated, merged and scaled using standard X-ray crystallography software to
      determine structures at atomic resolution. In this review we provide an overview
      of the MicroED method and compare it with other CryoEM methods.

PMID- 27701015
TI  - Synthesis of TiO2-N/SnO2 heterostructure photocatalyst and its photocatalytic
      mechanism.
AB  - A series of TiO2-N/SnO2X heterostructure photocatalysts were synthesized by a
      hydrolysis-deposition method. The structure, existing states of N and SnO2
      heterostructure at the interface of TiO2-N/SnO2X were studied by EADX, XRD,
      Raman, FT-IR, XPS, and HRTEM. The band structure is investigated by both
      theoretical calculation and experiment characterization. It was found that the
      introduction of NOx surface species and SnO2 nanoparticles would enhance the
      absorption in visible region, increase reactive oxidative species and separate
      photogenerated electrons and holes efficiently. Therefore, the photocatalytic
      activity is improved significantly for TiO2-N/SnO2X, compared with TiO2-N and
      TiO2 under visible and UV light irradiation. This work may offer a new strategy
      to fabricate new photocatalyst with high photocatalytic performance.

PMID- 27701016
TI  - Structural properties and release of insulin-loaded reverse hexagonal (HII)
      liquid crystalline mesophase.
AB  - Insulin loading into the HII mesophases was examined as a function of its
      concentration, with addition of glycerol as a cosolvent and with addition of
      phosphatidylcholine (PC) as a structural stabilizer. The structural properties,
      the molecular interactions, the viscoelastic properties, and the dynamic behavior
      were investigated by SAXS, ATR-FTIR, and rheological measurements. Insulin
      release was then monitored and analyzed. Insulin incorporation into the HII
      systems shrank the cylinders as it competed with the lipids in water-bonding.
      Insulin interrupted the interface while increasing taumax and creating a more
      solid-like response. Upon addition of PC, cooperative flow behavior was detected,
      which is probably the reason for increase in insulin cumulative release from 28%
      to 52% after 300 min. In the presence of glycerol, the system was less
      cooperative but insulin was more compactly folded, resulting in a slight
      improvement in insulin release (up to 6%). Addition of both PC and glycerol
      caused the maximum release (55%). The addition of additives into the HII system
      demonstrates how structural modifications can improve insulin release, and
      influence future design of encapsulated drug delivery systems.

PMID- 27701017
TI  - Design and application of sporopollenin microcapsule supported palladium
      catalyst: Remarkably high turnover frequency and reusability in catalysis of
      biaryls.
AB  - Bio-based catalyst support materials with high thermal and structural stability
      are desired for catalysts systems requiring harsh conditions. In this study, a
      thermally stable palladium catalyst (up to 440 degrees C) was designed from
      sporopollenin, which occurs naturally in the outer exine layer of pollens and is
      widely acknowledged as chemically very stable and inert biological material.
      Catalyst design procedure included (1) extraction of sporopollenin microcapsules
      from Betula pendula pollens (~25MUm), (2) amino-functionalisation of the
      microcapsules, (3) Schiff base modification and (4) preparation of Pd(II)
      catalyst. The catalytic activity of the sporopollenin microcapsule supported
      palladium catalyst was tested in catalysis of biaryls by following a fast, simple
      and green microwave-assisted method. We recorded outstanding turnover number
      (TON: 40,000) and frequency (TOF: 400,000) for the catalyst in Suzuki coupling
      reactions. The catalyst proved to be reusable at least in eight cycles. The
      catalyst can be suggested for different catalyst systems due to its thermal and
      structural durability, reusability, inertness to air and its eco-friendly nature.

PMID- 27701018
TI  - DIXDC1 promotes tumor proliferation and cell adhesion mediated drug resistance
      (CAM-DR) via enhancing p-Akt in Non-Hodgkin's lymphomas.
AB  - DIX domain containing 1 (DIXDC1), is a human homolog of Ccd1, a DIX domain
      containing protein in zebrafish. The present study was undertaken to determine
      the expression and biologic function of DIXDC1 in Non-Hodgkin's lymphoma (NHL).
      Clinically, we detected that the expression of DIXDC1 was significantly lower in
      the indolent lymphomas compared with the progressive lymphomas by
      immunohistochemistry analysis. Functionally, we found that DIXDC1 could promote
      cell proliferation via modulating cell cycle progression and PI3K/AKT signaling
      pathway in NHLs. Moreover, we confirmed that DIXDC1 was involved in the process
      of lymphoma cell adhesion mediated drug resistance (CAM-DR). Adhesion to
      fibronectin (FN) or HS-5 up-regulated DIXDC1 expression, and up-regulation of
      DIXDC1 resulted in an increased expression of p-AKT, which promoted CAM-DR. Our
      finding supports the role of DIXDC1 in cell proliferation, cell cycle and CAM-DR
      in NHLs. We propose that inhibition of DIXDC1 expression may be a novel
      therapeutic approach for NHLs patients, and it may be a target for drug
      resistance.

PMID- 27701019
TI  - Comparing the validity of the payment card and structured haggling willingness to
      pay methods: The case of a diabetes prevention program in rural Kenya.
AB  - BACKGROUND: The objective of this study was to compare the theoretical validity
      of two willingness-to-pay (WTP) methods, the commonly used payment card (PC) and
      the recently developed structured haggling (SH), for estimating the potential
      benefits of a diabetes prevention program in rural Kenya. METHODS: A convenience
      sample of adult residents from a rural county in Kenya (Kiambu), with no history
      of diabetes, was randomly assigned to one of two WTP methods, PC or SH, using
      structured face-to-face interviews from December 2011 to February 2012. RESULTS:
      A total of 376 respondents completed the interviews using PC (n = 185) or SH (n =
      191). More than 95% of respondents were willing to pay something for program
      access. The study showed that both methods were feasible in rural Kenya. SH
      resulted in a higher annual mean WTP than PC, Ksh504.05 (US$7.25) versus
      Ksh619.95 (US$5.90), respectively (p < 0.01). Based on theory, it was
      hypothesized that certain predisposing factors would result in greater WTP.
      Greater socio-economic status (measured using income proxies) resulted in greater
      unconditional WTP for both the PC and SH groups (t-tests and bivariate
      correlations) and conditional WTP (GLM models). GLM for PC showed being male,
      employed and having distant relatives with diabetes were significant predictors
      for WTP, while for SH being educated, employed and owning a vehicle were
      significant predictors. CONCLUSION: Both PC and SH showed theoretical validity in
      rural Kenya. However, the use of SH over PC in rural Kenya may be the better
      choice given that SH more closely mirrors marketplace transactions in this
      setting and the use of SH resulted in more significant variables in the GLM
      models.

PMID- 27701020
TI  - How much are built environments changing, and where?: Patterns of change by
      neighborhood sociodemographic characteristics across seven U.S. metropolitan
      areas.
AB  - Investments in neighborhood built environments could increase physical activity
      and overall health. Disproportionate distribution of these changes in advantaged
      neighborhoods could inflate health disparities. Little information exists on
      where changes are occurring. This paper aims to 1) identify changes in the built
      environment in neighborhoods and 2) investigate associations between high levels
      of change and sociodemographic characteristics. Using Geographic Information
      Systems, neighborhood land-use, local destinations (for walking, social
      engagement, and physical activity), and sociodemographics were characterized in
      2000 and 2010 for seven U.S. cities. Linear and change on change models estimated
      associations of built environment changes with baseline (2000) and change (2010
      2000) in sociodemographics. Spatial patterns were assessed using Global Moran's I
      to measure overall clustering of change and Local Moran's I to identify
      statistically significant clusters of high increases surrounded by high increases
      (HH). Sociodemographic characteristics were compared between HH cluster and other
      tracts using Analysis of Variance (ANOVA). We observed small land-use changes but
      increases in the destination types. Greater increases in destinations were
      associated with higher percentage non-Hispanic whites, percentage households with
      no vehicle, and median household income. Associations were present for both
      baseline sociodemographics and changes over time. Greater increases in
      destinations were associated with lower baseline percentage over 65 but higher
      increases in percentage over 65 between 2000 and 2010. Global Moran's indicated
      changes were spatially clustered. HH cluster tracts started with a higher
      percentage non-Hispanic whites and higher percentage of households without
      vehicles. Between 2000 and 2010, HH cluster tracts experienced increases in
      percent non-Hispanic white, greater increases in median household income, and
      larger decreases in percent of households without a vehicle. Changes in the built
      environment are occurring in neighborhoods across a diverse set of U.S.
      metropolitan areas, but are patterned such that they may lead to increased health
      disparities over time.

PMID- 27701022
TI  - DNA vaccine encoding molecular chaperone GroEL of Edwardsiella tarda confers
      protective efficacy against edwardsiellosis.
AB  - In the present study, molecular chaperone GroEL of Edwardsiella tarda was found
      both react with flounder (Paralichthys olivaceus) anti-recombinant GroEL (rGroEL)
      and anti-E. tarda antibodies, and it was both detected in the outer membrane and
      the secretome. To evaluate the vaccine potential of GroEL, pCI-neo-GFP-GroEL (pCG
      GroEL) was prepared and used to vaccinate healthy flounder, and immune protective
      effects were investigated. The results showed that pCG-GroEL produced an RPS of
      60% following E. tarda challenge at week 5 after immunization. Moreover, GroEL
      transcripts and GFP-tagged GroEL could be detected in vaccinated flounder after
      immunization with pCG-GroEL, and the GFP-tagged GroEL could be also detected in
      HINAE cells after transfection with pCG-GroEL. Meanwhile, the immune response of
      flounder induced by pCG-GroEL was investigated, and the results showed that: (1)
      the levels of specific serum antibodies against E. tarda induced by pCG-GroEL
      were significantly higher than other groups at 3-5 week post vaccination; (2) pCG
      GroEL could induce the proliferation of sIg+ lymphocytes, and the levels of sIg+
      lymphocytes in blood, spleen and pronephros of pCG-GroEL vaccinated fish were
      significantly increased compared with the PBS vaccinated fish at 3w, 2w and 2w
      after immunization, respectively; (3) MHCIalpha, MHCIIalpha, CD4-1, CD8alpha, IL
      1beta and TNF-alpha were significantly induced by immunization with pCG-GroEL,
      and the mRNA levels of CD4-1 and CD8alpha rapidly increased in pCG-GroEL
      vaccinated fish after challenge with E. tarda. Taking together, pCG-GroEL could
      elicit highly protective effects against E. tarda and induce strong immune
      response of flounder, suggesting that GroEL was a promising vaccine candidate.

PMID- 27701023
TI  - Workplace road safety risk management: An investigation into Australian
      practices.
AB  - In Australia, more than 30% of the traffic volume can be attributed to work
      related vehicles. Although work-related driver safety has been given increasing
      attention in the scientific literature, it is uncertain how well this knowledge
      has been translated into practice in industry. It is also unclear how current
      practice in industry can inform scientific knowledge. The aim of the research was
      to use a benchmarking tool developed by the National Road Safety Partnership
      Program to assess industry maturity in relation to risk management practices. A
      total of 83 managers from a range of small, medium and large organisations were
      recruited through the Victorian Work Authority. Semi-structured interviews aimed
      at eliciting information on current organisational practices, as well as policy
      and procedures around work-related driving were conducted and the data mapped
      onto the benchmarking tool. Overall, the results demonstrated varying levels of
      maturity of risk management practices across organisations, highlighting the need
      to build accountability within organisations, improve communication practices,
      improve journey management, reduce vehicle-related risk, improve driver
      competency through an effective workplace road safety management program and
      review organisational incident and infringement management. The findings of the
      study have important implications for industry and highlight the need to review
      current risk management practices.

PMID- 27701021
TI  - Endothelial adhesion molecules and multiple organ failure in patients with severe
      sepsis.
AB  - OBJECTIVE: To determine if serum levels of endothelial adhesion molecules were
      associated with the development of multiple organ failure (MOF) and in-hospital
      mortality in adult patients with severe sepsis. DESIGN: This study was a
      secondary data analysis of a prospective cohort study. SETTING: Patients were
      admitted to two tertiary intensive care units in San Antonio, TX, between 2007
      and 2012. PATIENTS: Patients with severe sepsis at the time of intensive care
      unit (ICU) admission were enrolled. Inclusion criteria were consistent with
      previously published criteria for severe sepsis or septic shock in adults.
      Exclusion criteria included immunosuppressive medications or conditions.
      INTERVENTIONS: None. MEASUREMENTS: Baseline serum levels of the following
      endothelial cell adhesion molecules were measured within the first 72h of ICU
      admission: Intracellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion
      Molecule-1 (VCAM-1), and Vascular Endothelial Growth Factor (VEGF). The primary
      and secondary outcomes were development of MOF (?2 organ dysfunction) and in
      hospital mortality, respectively. MAIN RESULTS: Forty-eight patients were
      enrolled in this study, of which 29 (60%) developed MOF. Patients that developed
      MOF had higher levels of VCAM-1 (p=0.01) and ICAM-1 (p=0.01), but not VEGF
      (p=0.70) compared with patients without MOF (single organ failure only). The area
      under the curve (AUC) to predict MOF according to VCAM-1, ICAM-1 and VEGF was
      0.71, 0.73, and 0.54, respectively. Only increased VCAM-1 levels were associated
      with in-hospital mortality (p=0.03). These associations were maintained even
      after adjusting for APACHE and SOFA scores using logistic regression.
      CONCLUSIONS: High levels of serum ICAM-1 was associated with the development of
      MOF. High levels of VCAM-1 was associated with both MOF and in-hospital
      mortality.

PMID- 27701024
TI  - A Bayesian procedure for evaluating the frequency of calibration factor updates
      in highway safety manual (HSM) applications.
AB  - The Highway Safety Manual (HSM) presents statistical models to quantitatively
      estimate an agency's safety performance. The models were developed using data
      from only a few U.S. states. To account for the effects of the local attributes
      and temporal factors on crash occurrence, agencies are required to calibrate the
      HSM-default models for crash predictions. The manual suggests updating
      calibration factors every two to three years, or preferably on an annual basis.
      Given that the calibration process involves substantial time, effort, and
      resources, a comprehensive analysis of the required calibration factor update
      frequency is valuable to the agencies. Accordingly, the objective of this study
      is to evaluate the HSM's recommendation and determine the required frequency of
      calibration factor updates. A robust Bayesian estimation procedure is used to
      assess the variation between calibration factors computed annually, biennially,
      and triennially using data collected from over 2400 miles of segments and over
      700 intersections on urban and suburban facilities in Florida. Bayesian model
      yields a posterior distribution of the model parameters that give credible
      information to infer whether the difference between calibration factors computed
      at specified intervals is credibly different from the null value which represents
      unaltered calibration factors between the comparison years or in other words,
      zero difference. The concept of the null value is extended to include the range
      of values that are practically equivalent to zero. Bayesian inference shows that
      calibration factors based on total crash frequency are required to be updated
      every two years in cases where the variations between calibration factors are not
      greater than 0.01. When the variations are between 0.01 and 0.05, calibration
      factors based on total crash frequency could be updated every three years.

PMID- 27701025
TI  - The effect of a nurse led telephone supportive care programme on patients'
      quality of life, received information and health care contacts after oesophageal
      cancer surgery-A six month RCT-follow-up study.
AB  - BACKGROUND: Following oesophagectomy, a major surgical procedure, it is known
      that patients suffer from severely reduced quality of life and have an unmet need
      for postoperative support. Still, there is a lack of research testing
      interventions aiming to enhance the patients' life situation after this surgical
      procedure. AIM: The aim of the study was to evaluate the effect of a nurse led
      telephone supportive care programme on quality of life (QOL), received
      information and the number of healthcare contacts compared to conventional care
      following oesophageal resection for cancer. METHOD: The study was designed as a
      randomized controlled trial (RCT) aiming to test the effect of a nurse led
      telephone supportive care program compared to conventional care. Patient
      assessments were conducted at discharge, 2 weeks, 2, 4 and 6 months after
      discharge and comprised evaluation of QOL, received information and the number of
      health care contacts. Statistical testing were conducted with repeated
      measurements analysis of variance to test if there were differences between the
      groups during follow-up. RESULT: The results show that the intervention group was
      significantly more satisfied with received information for items concerning the
      information they received about things to do to help yourself, written
      information and for the global information score. The control group scored
      significantly higher on the item regarding wishing to receive more information
      and wish to receive less information. No effect of the intervention was shown on
      QOL or number of health care contacts. CONCLUSION: Proactive nurse-led telephone
      follow-up has a significant positive impact on the patients' experience of
      received information. This is likely to have a positive effect on their ability
      to cope with a life that may include remaining side effects and adverse symptoms
      for a long time after surgery.

PMID- 27701026
TI  - Correspondence between adolescent and informant reports of substance use:
      Findings from the Philadelphia Neurodevelopmental Cohort.
AB  - Inclusion of collateral informant reports is common in adolescent psychopathology
      research and clinical assessment, yet few studies have examined agreement on
      ratings of adolescent substance use or factors that may be associated with
      reporter agreement. The present study aimed to extend prior work on the
      correspondence between adolescent and informant reports of adolescent substance
      use with data from a large (n=5214), diverse, community-based sample of youth
      aged 11-17 (mean age=14.53, SD=1.98; 52% female). Specifically, we examined: (a)
      agreement between adolescent and collateral informant reports of adolescent use
      of alcohol, marijuana, cocaine, inhalants, and stimulants and (b) potential
      correlates of reporter agreement. Agreement ranged from low (kappa=0.007,
      p=0.053) for inhalant use to moderate (kappa=0.414, p<0.001) for marijuana use.
      Disagreements were mainly driven by collateral underestimation of adolescent
      substance use. Older adolescent age was associated with poorer agreement across
      all substances (Odds Ratios [ORs]<=0.80, ps<0.05) except inhalants (OR=1.28,
      p<0.001). Reporter agreement on alcohol and marijuana use was lower for male than
      female adolescents (ORs<=0.85, ps<0.05). Adolescent psychopathology was
      associated with poorer agreement on all substances (ORs<=0.62, ps<0.01). For
      alcohol and marijuana, past year frequency of use was associated with better
      reporter agreement (ORs>=1.54, ps<0.001). For marijuana, older age at first use
      was related to poorer agreement (OR=0.81, p=0.01). Our results suggest that
      collateral reports of adolescent substance use may be ineffective proxies for
      adolescent self-reports in community samples, particularly for low base rate
      substances. Findings also highlight important factors to consider when collecting
      substance use information from multiple informants.

PMID- 27701027
TI  - Self-reported attentional and motor impulsivity are related to age at first
      methamphetamine use.
AB  - INTRODUCTION: Methamphetamine (MA) users report higher levels of impulsivity
      relative to healthy controls, which may either result from, or precede, their
      substance use. Further, there is evidence that female MA users may be more
      impulsive than male MA users prior to MA use. Thus, the goal of the current study
      was to determine whether different subtraits of self-reported impulsivity are
      significantly related to age at first MA use, controlling for total years of MA
      use. METHODS: A community sample of MA users was recruited for this study (N=157;
      113 males, 44 females). The Barratt Impulsiveness Scale (BIS-11) was used to
      assess self-reported impulsivity on three subscales (Attentional, Motor, Non
      planning). Age at first MA use served as the dependent variable in a series of
      multiple regression models with BIS-11 subscales, sex, and their interaction as
      independent variables, controlling for total years of MA use. RESULTS:
      Attentional and Motor impulsivity were significantly related to age at first MA
      use when controlling for total years of MA use (Attentional: p=0.008; Motor:
      p=0.003). CONCLUSIONS: Individuals who reported higher Attentional and Motor
      impulsivity started using MA at an earlier age, which could suggest that
      impulsivity levels may be an important marker of vulnerability towards MA use.
      These findings indicate that prevention efforts may be targeted towards
      individuals who report high levels of Attentional and Motor impulsivity, as they
      may be at greatest risk for earlier initiation of MA use.

PMID- 27701028
TI  - Prediction of intramuscular fat content using CT scanning of packaged lamb cuts
      and relationships with meat eating quality.
AB  - Novel, multi-object X-ray computed tomography (CT) methodologies can individually
      analyse vacuum-packed meat samples scanned in batches of three or more, saving
      money and time compared to scanning live animals. If intramuscular fat (IMF), as
      a proxy for meat quality, can be predicted with similar accuracies as in live
      lambs, this method could be used to grade on quality, or to inform breeding
      programmes. Lamb loin cuts from commercial carcasses (n=303), varying in fat and
      conformation grade, were vacuum-packed and CT scanned, then tested for meat
      quality traits and by a trained taste panel. Tissue density values measured by
      CT, alongside carcass and loin weights, predicted IMF with moderate accuracy (R2
      0.36), but did not accurately predict shear force or sensory traits. Juiciness
      and flavour increased linearly with IMF, whilst texture and overall liking
      increased to an optimum between 4 and 5% IMF. Samples predicted by CT as having
      >3% IMF scored significantly higher for sensory traits, than those predicted as
      <3% IMF.

PMID- 27701030
TI  - The relationship between educational stress, stress coping, self-esteem, social
      support, and health status among nursing students in Turkey: A structural
      equation modeling approach.
AB  - BACKGROUND: Nursing education can be a stressful experience. To fully benefit
      from this experience and develop a positive professional identity, it is
      essential for nursing students to effectively cope with education-related stress.
      PURPOSE: The aim of the study was to investigate the relationships between
      nursing students' education-related stress and stress coping, self-esteem, social
      support, and health status. METHOD: This study utilized a cross-sectional,
      descriptive, and correlational design. The sample consisted 517 nursing students
      from a bachelor program in Turkey during the 2014-2015 academic year.
      Participants provided data on sociodemographic characteristics as well as
      completing the following instruments: Nursing Education Stress Scale, Coping
      Behavior Inventory for Nursing Students, Multidimensional Scale of Perceived
      Social Support, Rosenberg Self-Esteem Scale, and General Health Questionnaire.
      Relationships were examined using multivariate structural equation modeling.
      RESULTS: Results indicated that nursing students' stress coping levels were
      affected by self-esteem and social support. Additionally, this interaction
      appears to affect general health status. Although the direct effect of stress on
      coping was non-significant, its overall effect was significant within the model.
      CONCLUSION: It is necessary to conduct further intervention studies examining the
      role of self-esteem and social support in facilitating nursing students' stress
      related coping during their education.

PMID- 27701029
TI  - Epilepsy, amyloid-beta, and D1 dopamine receptors: a possible pathogenetic link?
AB  - Experimental and clinical observations indicate that amyloid-beta1-42 (Abeta1-42)
      peptide not only represents a major actor in neurodegenerative mechanisms but
      also induce hyperexcitation in individual neurons and neural circuits. In this
      abnormal excitability, possibly leading to seizures, the D1 dopamine (DA)
      receptors may play a role. Cerebrospinal fluid levels of Abeta1-42 were measured
      in patients with late-onset epilepsy of unknown etiology. Moreover, the effect of
      amyloid peptide on the hippocampal epileptic threshold and synaptic plasticity
      and its link to D1 receptor function were tested in experimental mouse model of
      cerebral amyloidosis and in acute model of Abeta1-42-induced neurotoxicity. Among
      272 evaluated epileptic patients, aged >55 years, 35 suffered from late-onset
      epilepsy of unknown etiology. In these subjects, cerebrospinal fluid Abeta1-42
      levels were measured. The effects of Abeta1-42, amyloid oligomers, and D1
      receptor modulation on epileptic threshold were analyzed by electrophysiological
      recordings in the dentate gyrus of mice hippocampal slices. We found that Abeta1
      42 levels were significantly decreased in cerebrospinal fluid of patients with
      late-onset epilepsy of unknown etiology with respect to controls suggesting the
      cerebral deposition of this peptide in these patients. Abeta1-42 enhanced
      epileptic activity in mice through a mechanism involving increased surface
      expression of D1 receptor, and this effect was mimicked by D1 receptor
      stimulation and blocked by SCH 23390, a D1 receptor antagonist. Abeta1-42 may
      contribute to the pathophysiology of late-onset epilepsy of unknown origin. Our
      preclinical findings indicate that the D1 receptor is involved in mediating the
      epileptic effects of Abeta1-42. This novel link between Abeta1-42 and D1 receptor
      signaling might represent a potential therapeutic target.

PMID- 27701031
TI  - Novel selective TOCSY method enables NMR spectral elucidation of metabolomic
      mixtures.
AB  - Complex mixture analysis is routinely encountered in NMR-based investigations.
      With the aim of component identification, spectral complexity may be addressed
      chromatographically or spectroscopically, the latter being favored to reduce
      sample handling requirements. An attractive experiment is selective total
      correlation spectroscopy (sel-TOCSY), which is capable of providing tremendous
      spectral simplification and thereby enhancing assignment capability.
      Unfortunately, isolating a well resolved resonance is increasingly difficult as
      the complexity of the mixture increases and the assumption of single spin system
      excitation is no longer robust. We present TOCSY optimized mixture elucidation
      (TOOMIXED), a technique capable of performing spectral assignment particularly in
      the case where the assumption of single spin system excitation is relaxed. Key to
      the technique is the collection of a series of 1D sel-TOCSY experiments as a
      function of the isotropic mixing time (taum), resulting in a series of resonance
      intensities indicative of the underlying molecular structure. By comparing these
      taum-dependent intensity patterns with a library of pre-determined component
      spectra, one is able to regain assignment capability. After consideration of the
      technique's robustness, we tested TOOMIXED firstly on a model mixture. As a
      benchmark we were able to assign a molecule with high confidence in the case of
      selectively exciting an isolated resonance. Assignment confidence was not
      compromised when performing TOOMIXED on a resonance known to contain multiple
      overlapping signals, and in the worst case the method suggested a follow-up sel
      TOCSY experiment to confirm an ambiguous assignment. TOOMIXED was then
      demonstrated on two realistic samples (whisky and urine), where under our
      conditions an approximate limit of detection of 0.6mM was determined. Taking into
      account literature reports for the sel-TOCSY limit of detection, the technique
      should reach on the order of 10MUM sensitivity. We anticipate this technique will
      be highly attractive to various analytical fields facing mixture analysis,
      including metabolomics, foodstuff analysis, pharmaceutical analysis, and
      forensics.

PMID- 27701032
TI  - Four pulse recoupling.
AB  - The paper describes a family of novel recoupling pulse sequences in magic angle
      spinning (MAS) solid state NMR, called four pulse recoupling. These pulse
      sequences can be employed for both homonuclear and heteronuclear recoupling
      experiments and are robust to dispersion in chemical shifts and rf-inhomogeneity.
      The homonuclear pulse sequence consists of a building block pi20 degrees 3pi2phi
      degrees pi2180 degrees +phi degrees 3pi2180 degrees  where phi=pinphi degrees
      =180 degrees n, and n is number of blocks in a two rotor period. The
      heteronuclear recoupling pulse sequence consists of a building block [Formula:
      see text] and [Formula: see text] on channel I and S, where phi1=3pi2n,phi2=pi2n
      and n is number of blocks in a two rotor period. The recoupling pulse sequences
      mix the y magnetization. We show that four pulse recoupling is more broadband
      compared to three pulse recoupling [1]. Experimental quantification of this
      method is shown for 13Calpha-13CO, homonuclear recoupling in a sample of Glycine
      and 15N-13Calpha, heteronuclear recoupling in Alanine. Application of this method
      is demonstrated on a sample of tripeptide N-formyl-[U-13C,15N]-Met-Leu-Phe-OH
      (MLF).

PMID- 27701033
TI  - Norovirus infections in a tertiary care centre - individual cases do not
      necessarily lead to an outbreak.
AB  - BACKGROUND: Norovirus is responsible for the majority of gastroenteritis
      outbreaks within healthcare settings. Routes of spread include foodborne-,
      waterborne- and especially person-to-person transmissions. OBJECTIVE: We
      investigated the overall attack rate of norovirus, within and outside outbreak
      situations, transmitted via patient-to-patient contact in a tertiary care centre
      from January 2012 to March 2015. STUDY DESIGN: We monitored exposed asymptomatic
      patients next to infectious patients for the development of symptoms of acute
      gastroenteritis following exposure. RESULTS: We detected 102 patients with
      contact to 94 infectious patients. Of these only 11 patients developed typical
      norovirus symptoms after exposure while 91 patients remained asymptomatic. Total
      secondary attack rate was only 10.8%. CONCLUSIONS: Patient-to-patient
      transmission of norovirus is potentially overestimated within clinical settings.
      Future prevention strategies should consider personal risk factors of exposed
      patients.

PMID- 27701034
TI  - Asymmetry in gait pattern following tibial shaft fractures - a prospective one
      year follow-up study of 49 patients.
AB  - INTRODUCTION: Despite the high number of studies evaluating the outcomes
      following tibial shaft fractures, the literature lacks studies including
      objective assessment of patients' recovery regarding gait pattern. The purpose of
      the present study was to evaluate whether gait patterns at 6 and 12 months post
      operatively following intramedullary nailing of a tibial shaft fracture are
      different compared with a healthy reference population. PATIENTS AND METHODS: The
      study design was a prospective cohort study. The primary outcome measurement was
      the gait patterns at 6 and 12 months post-operatively measured with a 6-metre
      long pressure-sensitive mat. The mat registers footprints and present gait speed,
      cadence as well as temporal and spatial parameters of the gait cycle. Gait
      patterns were compared to a healthy reference population. RESULTS: 49 patients
      were included with a mean age of 43.1 years (18-79 years). Forty-three patients
      completed the 12-month follow-up (88%). Gait speed and cadence were significantly
      increased between the 6- and 12-month follow-up (P<0.001). At 6-month follow-up,
      patients showed considerable asymmetry in the injured leg compared with the non
      injured leg: single-support time 12.8% shorter, swing-time 12.8% longer, step
      length 11.9% shorter, and rotation of the foot increased by 32.3%. At the 12
      month follow-up, gait asymmetry become almost normalized compared to a healthy
      reference group. CONCLUSION: In patients treated by intramedullary nailing
      following a tibial shaft fracture, gait asymmetry accompanied with slower speed
      and cadence are common during the first 6 months and become normalized compared
      with a healthy reference population between 6 and 12 months post-operatively.

PMID- 27701035
TI  - A test of fixed and moving reference point control in posture.
AB  - This study investigated two contrasting assumptions of the regulation of posture:
      namely, fixed and moving reference point control. These assumptions were tested
      in terms of time-dependent structure and data distribution properties when
      stability is manipulated. Fifteen male participants performed a tightrope
      simulated balance task that is, maintaining a tandem stance while holding a pole.
      Pole length (and mass) and the standing support surface (fixed surface/balance
      board) were manipulated so as to mechanically change the balance stability. The
      mean and standard deviation (SD) of COP length were reduced with pole length
      increment but only in the balance board surface condition. Also, the SampEn was
      lower with greater pole length for the balance board but not the fixed surface.
      More than one peak was present in the distribution of COP in the majority of
      trials. Collectively, the findings provide evidence for a moving reference point
      in the maintenance of postural stability for quiet standing.

PMID- 27701036
TI  - Perceiving slipperiness and grip: A meaningful relationship of the shoe-ground
      interface.
AB  - The present study investigated the relationship between objective measurements of
      the available (CoFA), the utilized (CoFU) coefficient of friction and subjective
      perception of grip or slipperiness. It was hypothesized that significant
      correlations exist between the perception of grip or slip and the CoF during
      sports movement and that a minimum CoF was needed to ensure an optimal
      grip/slipperiness perception. Eighteen healthy active females performed forward
      and backward cutting tasks onto a forceplate. Six shoes and two floors were used
      to induce different grip conditions. Subjective ratings and CoFU were assessed
      for each shoe-floor combination, and mechanical CoFA was also measured in a
      specific test bed. Significant relationships (p<0.001) were found between grip,
      slipperiness ratings or CoFA with the CoFU (r=0.98, r=-0.97, r=0.88,
      respectively). Individual sensory thresholds of the minimum required CoFU were
      also determined using probit models between the CoFU and the grip acceptability.
      The mean threshold defined in the present study was 0.70+/-0.11. This meant that
      below this threshold, the grip perception was not acceptable, whereas above this
      threshold, the grip was felt good enough to perform the task. In conclusion,
      strong relationships between subjective perceptions and objective measurements of
      friction were found in sports-like movements. Moreover, a minimum friction
      requirement was defined for indoor dry shoe-floor conditions. The present study
      gives new insights of the shoe-floor interaction and outlines friction
      requirements for the manufacturers of sports floor or footwear.

PMID- 27701037
TI  - Simultaneous determination of phenolic acids and flavonoids in Chenopodium
      formosanum Koidz. (djulis) by HPLC-DAD-ESI-MS/MS.
AB  - A high performance liquid chromatography-diode array detection-tandem mass
      spectrometry method (HPLC-DAD-MS/MS) was developed for simultaneous determination
      of phenolic acids and flavonoids in djulis (Chenopodium formosanum Koidz.), a
      traditional Chinese herb reported to possess vital biological activities. A high
      yield of phenolic acids and flavonoids was attained by employing 50% ethanol in
      water as the extraction solvent and shaking in a 60 degrees C water bath for 3h.
      A total of 8 phenolic acids and 14 flavonoids were separated and identified
      within 55min by using a Poroshell 120 EC-C18 column with detection at 280nm, flow
      rate at 0.8mL/min, column temperature at 35 degrees C, and a gradient solvent
      system of 0.1% formic acid in water and acetonitrile. Two internal standards
      caffeic acid and kaempferol-3-O-rutinoside were used for quantitation of phenolic
      acids and flavonoids in djulis respectively. The amounts of phenolic acids ranged
      from 11.5+/-0.8MUg/g (caffeoyl-putrescine-derivative (2)) to 1855.3+/-16.9MUg/g
      (hydroxylphenylacetic acid pentoside), while the flavonoids ranged from 19.93+/
      2.29MUg/g (quercetin-3-O-(coumaryl)-rutinoside-pentoside (1)) to 257.3+/
      2.05MUg/g (rutin-O-pentoside (2)). A high recovery (89.68-97.20%) and high
      reproducibility was obtained for both phenolic acids and flavonoids with the
      relative standard deviation (RSD) for the latter ranging from 0.09-8.22% (intra
      day variability) and 0.80-8.48% (inter-day variability). This method may be
      applied to determination of both phenolic acids and flavonoids in food products
      and Chinese herbs.

PMID- 27701039
TI  - Central skull base osteomyelitis involving cavernous sinus and meninges of the
      skull base: Successful treatment with antibiotic and antifungal combination
      therapy.

PMID- 27701038
TI  - Analysis of fenretinide and its metabolites in human plasma by liquid
      chromatography-tandem mass spectrometry and its application to clinical
      pharmacokinetics.
AB  - A simple and accurate high-performance liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method was developed for the determination of N-(4
      hydroxyphenyl)retinamide (fenretinide, 4-HPR) and its metabolites, 4-oxo-N-(4
      hydroxyphenyl)retinamide (4-oxo-4-HPR) and N-(4-methoxyphenyl)retinamide (4-MPR),
      in human plasma. Plasma samples were prepared using protein precipitation with
      ethanol. Chromatographic separation of the three analytes and N-(4
      ethoxyphenyl)retinamide (4-EPR), an internal standard, was achieved on a Zorbax
      SB-C18 column (3.5MUm, 50*2.1mm) using gradient elution with the mobile phase of
      0.1% formic acid in water and acetonitrile (pH* 2.4) at a flow rate of 0.5mL/min.
      Electrospray ionization (ESI) mass spectrometry was operated in the positive ion
      mode with multiple reaction monitoring (MRM). The calibration curves obtained
      were linear over the concentration range of 0.2-50ng/mL with a lower limit of
      quantification of 0.2ng/mL. The relative standard deviation of intra-day and
      inter-day precision was below 7.64%, and the accuracy ranged from 94.92 to
      105.43%. The extraction recoveries were found to be higher than 90.39% and no
      matrix effect was observed. The analytes were stable for the durations of the
      stability studies. The validated method was successfully applied to the analyses
      of the pharmacokinetic study for patients treated with 4-HPR in a clinical trial.

PMID- 27701040
TI  - Impact of neonatal risk and temperament on behavioral problems in toddlers born
      preterm.
AB  - Children born preterm are at risk for later developmental disorders. The present
      study examined the predictive effects of neonatal, sociodemographic, and
      temperament characteristics on behavioral outcomes at toddlerhood, in children
      born preterm. The sample included 100 toddlers born preterm and with very-low
      birth-weight, and their mothers. Neonatal characteristics were evaluated using
      medical records. The mothers were interviewed using the Early Childhood Behavior
      Questionnaire for temperament assessment, and the Child Behavior Checklist for
      behavioral assessment. Multiple linear regression analyses were performed.
      Predictors of 39% of the variability of the total behavioral problems in toddlers
      born prematurely were: temperament with more Negative Affectivity and less
      Effortful Control, lower family socioeconomic status, and younger mothers at
      childbirth. Temperament with more Negative Affectivity and less Effortful Control
      and lower family socioeconomic status were predictors of 23% of the variability
      of internalizing behavioral problems. Additionally, 37% of the variability of
      externalizing behavioral problems was explained by temperament with more Negative
      Affectivity and less Effortful Control, and younger mothers at childbirth. The
      neonatal characteristics and stressful events in the neonatal intensive care unit
      did not predict behavioral problems at toddlerhood. However, temperament was a
      consistent predictor of behavioral problems in toddlers born preterm. Preventive
      follow-up programs could assess dispositional traits of temperament to provide
      early identification of preterm infants at high-risk for behavioral problems.

PMID- 27701041
TI  - Changes in alcohol use following the transition to motherhood: Findings from the
      National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - BACKGROUND: Little is known about the impact of motherhood on alcohol use beyond
      the acute reductions observed in pregnancy. This study characterizes changes in
      alcohol use for women who did and did not become mothers over three years.
      METHODS: Data are from the National Epidemiologic Survey of Alcohol and Related
      Conditions (NESARC). Participants were female respondents aged 18-44 years who
      did not have children and were not pregnant at wave 1, and who reported having at
      least one drink in the year prior to wave 1 (n=2118). Women were classified as
      mothers (n=325) if they reported having a child between waves 1 and 2, and non
      mothers if they did not (n=1793). At each wave, participants provided information
      on past-year frequency of alcohol use and heavy episodic drinking, and usual
      number of alcoholic beverages consumed per occasion. RESULTS: At baseline, women
      who did and did not become mothers reported similar levels of alcohol use. Women
      who became mothers reported significant reductions in alcohol use indicators from
      wave 1 to wave 2 (i.e., 22 fewer drinking days, 15 fewer heavy drinking days, 1
      less drink per occasion), whereas women who did not become mothers showed a
      modest increase in alcohol use frequency (i.e., 7 more drinking days). Motherhood
      remained significantly associated with reductions in alcohol use after adjusting
      for sociodemographic variables and baseline alcohol use. CONCLUSIONS: The
      transition to motherhood is associated with marked reductions in alcohol
      consumption. Similar reductions were not observed for women who did not become
      mothers.

PMID- 27701043
TI  - Single awakening salivary measurements provide reliable estimates of morning
      cortisol levels in pregnant women.
AB  - Mood disorders during pregnancy have been associated with adverse effects on
      maternal as well as fetal health. Since mood, anxiety, and stress disorders are
      related with elevated cortisol levels, salivary cortisol may be a useful
      biomarker. Although multiple samples are generally recommended, a single
      measurement of awakening salivary cortisol could be a simpler and more cost
      effective method to determine whether women have elevated morning cortisol levels
      during a specific period of pregnancy. Therefore, the aim of this validation
      study among 177 women in the PRIDE Study was to examine whether one awakening
      salivary cortisol measurement will suffice to classify pregnant women as having
      normal or elevated cortisol levels compared to awakening salivary cortisol
      measurements on three consecutive working days. We calculated intraclass
      correlation coefficients (ICC) and Cohen's kappa statistics (kappa) overall as
      well as in sub-analyses within strata based on maternal age, level of education,
      net household income, pre-pregnancy BMI, parity, complications during pregnancy,
      caffeine consumption, gestational week of sampling, and awakening time. The mean
      cortisol concentrations were 8.98ng/ml (SD 5.32) for day one, 8.62ng/ml (SD 4.55)
      for day two, and 8.39ng/ml (SD 4.58) for day three. The overall ICC was 0.86 (95%
      CI 0.82-0.89) while the kappa was 0.75 (95% CI 0.64-0.86). For the ICCs
      calculated within sub-analyses, a maximum difference of 0.11 was observed between
      the strata. For the kappa statistics, most strata did not differ more than 0.12,
      except for pre-pregnancy BMI, severe nausea, and extreme fatigue with differences
      up to 0.22. In conclusion, one awakening salivary cortisol measurement is as
      reliable for the classification of pregnant women into normal and elevated
      morning cortisol levels as salivary cortisol measurements on three consecutive
      working days.

PMID- 27701042
TI  - Methadone maintenance therapy and viral suppression among HIV-infected opioid
      users: The impacts of crack and injection cocaine use.
AB  - BACKGROUND: Methadone maintenance therapy (MMT) is associated with improved HIV
      treatment outcomes among people who use drugs (PWUD). The extent to which these
      benefits are sustained in the context of ongoing cocaine use is unclear. We
      assessed differential impacts of MMT on HIV viral load (VL) suppression in
      relation to discrete patterns of cocaine use. METHODS: Data was drawn from
      ACCESS, a prospective cohort of HIV-positive PWUD in Vancouver, Canada.
      Generalized linear mixed-effects were used to model the independent effect of MMT
      on VL suppression across strata of frequency of cocaine injection and crack
      smoking (>=daily versus <daily), after adjustment for confounders. RESULTS: The
      analysis included 397 HIV-positive opioid users who completed >=1 study interview
      between 2005 and 2014. At baseline, 304 (77%) reported participation in MMT, 37
      (9%) >=daily cocaine injection, and 158 (40%) >=daily crack smoking. In adjusted
      analyses, MMT remained independently associated with increased odds of VL
      suppression in both strata of crack smokers (AOR=3.11, 95% CI: 1.86-5.21 and
      AOR=1.48, 95%CI: 1.04-2.09, for >=daily and <daily smokers, respectively), and
      among <daily cocaine injectors (AOR=1.88, 95%CI 1.38-2.56), but not among >=daily
      cocaine injectors (AOR=1.37, 95%CI 0.53-3.49). Longer retention on MMT was
      positively associated with VL suppression in all strata of cocaine injection and
      crack smoke. CONCLUSIONS: Exposure to MMT was associated with increased odds of
      VL suppression among HIV- positive opioid users regardless of crack use. However,
      this beneficial effect of MMT was lost among frequent cocaine injectors with
      shorter retention on MMT.

PMID- 27701044
TI  - Corticotropin-releasing hormone induces depression-like changes of sleep
      electroencephalogram in healthy women.
AB  - We reported previously that repetitive intravenous injections of corticotropin
      releasing hormone (CRH) around sleep onset prompt depression-like changes in
      certain sleep and endocrine activity parameters (e.g. decrease of slow-wave sleep
      during the second half of the night, blunted growth hormone peak, elevated
      cortisol concentration during the first half of the night). Furthermore a sexual
      dimorphism of the sleep-endocrine effects of the hormones growth hormone
      releasing hormone and ghrelin was observed. In the present placebo-controlled
      study we investigated the effect of pulsatile administration of 4*50MUg CRH on
      sleep electroencephalogram (EEG) and nocturnal cortisol and GH concentration in
      young healthy women. After CRH compared to placebo, intermittent wakefulness
      increased during the total night and the sleep efficiency index decreased. During
      the first third of the night, REM sleep and stage 2 sleep increased and sleep
      stage 3 decreased. Cortisol concentration was elevated throughout the night and
      during the first and second third of the night. GH secretion remained unchanged.
      Our data suggest that after CRH some sleep and endocrine activity parameters show
      also depression-like changes in healthy women. These changes are more distinct in
      women than in men.

PMID- 27701045
TI  - The consequences of having a dominant romantic partner on testosterone responses
      during a social interaction.
AB  - Testosterone reactivity has been conceptualized as a marker of social submission
      at low levels and social dominance at high levels. However, hormonal fluctuations
      in response to romantic partners remain largely unknown. Towards this end, 88
      couples (N=176) discussed an emotional video. Prior to the conversation, one
      member of the dyad (the "agent") was instructed to regulate affective displays in
      a specific way (express or suppress). The other dyad member (the "partner") was
      given no special instruction and was unaware of regulation instructions given to
      the agent. Agents who regulated affective displays were expected to exhibit
      decreased testosterone from baseline because they were prevented from tuning
      their emotional responses to their partners. Furthermore, we expected declines in
      testosterone would be moderated by partners' authoritativeness: People would be
      particularly submissive to more dominant partners. Predictions were supported for
      females and partially supported for males. Agents exhibited decreases in
      testosterone from baseline relative to partners. For females, this main effect
      was moderated by partners' trait-level authoritativeness: Females interacting
      with partners higher in authority exhibited larger decreases in testosterone when
      instructed to restrict their emotion regulation strategies. This research is the
      first to document testosterone reactivity in existing romantic relationships and
      underscores the importance of taking into account social and relational contexts
      when examining hormonal regulation.

PMID- 27701047
TI  - Spectrophotometric determination of gold(III) in forensic and pharmaceutical
      samples and results complemented with ICP AES and EDXRF analysis.
AB  - Spectrophotometric method with three systems were developed here for the
      determination of gold(III) using o-dianisidine, aniline sulphate and catechol.
      Gold(III),in the system 1 it oxidizes o-dianisidine, in the system 2 it oxidizes
      catechol followed by its coupling with o-dianisidine, in the system 3 it oxidizes
      catechol followed by its coupling with aniline sulphate forming dye products with
      respective lambdamax 446nm, 540nm, and 505nm. All the three systems were
      optimized and analytical parameters were calculated. The molar absorptivity
      values were 9.27*104, 1.97*104 and 1.62*104 respectively for the systems 1, 2 and
      3 with the corresponding Sandell sensitivity values (MUgcm-2), 0.0021, 0.0096 and
      0.011. The optimized systems were used for the determination of gold present in
      some forensic jewellery and pharmaceutical samples and the results obtained were
      compared with the results of all samples determined by Inductively Coupled Plasma
      - Atomic Emission Spectrometric method and a few of them were also complemented
      by Energy Dispersive X-Ray Fluorescent spectral analysis.

PMID- 27701046
TI  - Preoperative prediction of temporal lobe epilepsy surgery outcome.
AB  - PURPOSE: There is controversy about relative contributions of ictal scalp video
      EEG recording (vEEG), routine scalp outpatient interictal EEG (rEEG),
      intracranial EEG (iEEG) and MRI for predicting seizure-free outcomes after
      temporal lobectomy. We reviewed NIH experience to determine contributions at
      specific time points as well as long-term predictive value of standard pre
      surgical investigations. METHODS: Raw data was obtained via retrospective chart
      review of 151 patients. After exclusions, 118 remained (median 5 years follow
      up). MRI-proven mesial temporal sclerosis (MTSr) was considered a separate
      category for analysis. Logistic regression estimated odds ratios at 6-months, 1
      year, and 2 years; proportional hazard models estimated long-term comparisons.
      Subset analysis of the proportional hazard model was performed including only
      patients with commonly encountered situations in each of the modalities, to
      maximize statistical inference. RESULTS: Any MRI finding, MRI proven MTS, rEEG,
      vEEG and iEEG did not predict two-year seizure-free outcome. MTSr was predictive
      at six months (OR=2.894, p=0. 0466), as were MRI and MTSr at one year
      (OR=10.4231, p=0. 0144 and OR=3.576, p=0. 0091). Correcting for rEEG and MRI,
      vEEG failed to predict outcome at 6 months, 1year and 2 years. Proportional
      hazard analysis including all available follow-up failed to achieve significance
      for any modality. In the subset analysis of 83 patients with commonly encountered
      results, vEEG modestly predicted long-term seizure-free outcomes with a
      proportional hazard ratio of 1.936 (p=0.0304). CONCLUSIONS: In this study,
      presurgical tools did not provide unambiguous long-term outcome predictions.
      Multicenter prospective studies are needed to determine optimal presurgical
      epilepsy evaluation.

PMID- 27701048
TI  - Cobalt iron oxide nanoparticles induce cytotoxicity and regulate the apoptotic
      genes through ROS in human liver cells (HepG2).
AB  - Cobalt iron oxide (CoFe2O4) nanoparticles (CIO NPs) have been one of the most
      widely explored magnetic NPs because of their excellent chemical stability,
      mechanical hardness and heat generating potential. However, there is limited
      information concerning the interaction of CIO NPs with biological systems. In
      this study, we investigated the reactive oxygen species (ROS) mediated
      cytotoxicity and apoptotic response of CIO NPs in human liver cells (HepG2).
      Diameter of crystalline CIO NPs was found to be 23nm with a band gap of 1.97eV.
      CIO NPs induced cell viability reduction and membrane damage, and degree of
      induction was dose- and time-dependent. CIO NPs were also found to induce
      oxidative stress revealed by induction of ROS, depletion of glutathione and lower
      activity of superoxide dismutase enzyme. Real-time PCR data has shown that mRNA
      level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9)
      were higher, while the expression level of anti-apoptotic gene bcl-2 was lower in
      cells following exposure to CIO NPs. Activity of caspase-3 and caspase-9 enzymes
      was also higher in CIO NPs exposed cells. Furthermore, co-exposure of N-acetyl
      cysteine (ROS scavenger) efficiently abrogated the modulation of apoptotic genes
      along with the prevention of cytotoxicity caused by CIO NPs. Overall, we observed
      that CIO NPs induced cytotoxicity and apoptosis in HepG2 cells through ROS via
      p53 pathway. This study suggests that toxicity mechanisms of CIO NPs should be
      further investigated in animal models.

PMID- 27701049
TI  - Soluble curcumin amalgamated chitosan microspheres augmented drug delivery and
      cytotoxicity in colon cancer cells: In vitro and in vivo study.
AB  - In present investigation, initially curcumin was complexed with 2-HP-beta-CD
      (curcumin-2-HP-beta-CD-complex) in 1:1 ratio and later amalgamated with chitosan
      microspheres (curcumin-2-HP-beta-CD-CMs) for selective delivery in colon only
      through oral route of administration. Various analytical, spectral and in-silico
      docking techniques revealed that the curcumin was deeply inserted in the 2-HP
      beta-CD cavity with apparent stability constant of 3.35*10-3M. Furthermore, the
      mean particle size of 6.8+/-2.6MUm and +39.2+/-4.1mV surface charge of curcumin-2
      HP-beta-CD-complex-CMs in addition to encapsulation efficiency of about 79.8+/
      6.3% exhibited that the tailored microspheres were optimum for colon delivery of
      curcumin. This was also demonstrated in dissolution testing and standard cell
      proliferation assay in which curcumin-2-HP-beta-CD-complex-CMs exhibited maximum
      release in simulated colonic fluid (SCF, pH ~7.0-8.0, almond emulsion-beta
      glucosidase) with improved therapeutic index in HT-29 cells. Consistently,
      curcumin-2-HP-beta-CD-complex-CMs successively enhanced the colonic bio
      distribution of curcumin by ~8.36 folds as compared to curcumin suspension in
      preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-beta-CD-complex
      CMs warrant further in vivo tumor regression study to establish its therapeutic
      efficacy in experimental colon cancer.

PMID- 27701050
TI  - S-nitroso-N-acetyl penicillamine inhibits spontaneous exit from metaphase-II
      arrest in rat eggs cultured in vitro.
AB  - BACKGROUND: Present study was designed to investigate the in vitro effects of
      nitric oxide (NO) donor such as S-nitroso-N-acetyl penicillamine (SNAP) on
      spontaneous exit from metaphase-II arrest (SEM-II) in rat eggs cultured in vitro.
      METHODS: Ovulated eggs were denuded and then exposed to various concentrations
      (0.0, 0.01, 0.1 and 1.0mM) of SNAP for 3h under in vitro culture conditions. The
      percentage of SEM-II, specific and total phosphorylated cyclin-dependent kinase-1
      (Cdk1), cyclin B1 and anaphase promoting complex/cyclosome (APC/C) levels as well
      as Cdk1 activity were analyzed. RESULTS: The SEM-II was associated with a
      decrease of Thr-161 phosphorylated Cdk1 as well as cyclin B1 levels and increase
      of Thr-14/Tyr-15 phosphorylated Cdk1, APC/C levels and Cdk1 activity in aged eggs
      cultured in vitro. On the other hand, SNAP treatment prevented a decrease of Thr
      161 phosphorylated Cdk1 as well as cyclin B1 levels and increase of Thr-14/Tyr-15
      phosphorylated Cdk1, Cdk1 activity that finally prevented SEM-II in a
      concentration-dependent manner. However, APC/C level was not affected by SNAP
      during the course of treatment in vitro. CONCLUSIONS: Present data suggest that
      SNAP prevented SEM-II possibly by increasing high level of NO and thereby
      maturation promoting factor (MPF) stabilization in rat eggs cultured in vitro.
      Hence, SNAP could be used to prevent SEM-II that reduces reproductive outcome in
      several mammalian species.

PMID- 27701051
TI  - New insight on using aged garlic extract against toxic impacts of titanium
      dioxide bulk salt triggers inflammatory and fibrotic cascades in male rats.
AB  - The efficacy of aged garlic extract (AGE) in alleviating the hepatic inflammation
      and pulmonary fibrotic responses induced by titanium dioxide (TiO2) toxicity was
      studied. The control group received distilled water. AGE-treated group received
      AGE (2ml/kgbw). TiO2- intoxicated group received TiO2 (5g/kgbw). AGE combined
      with TiO2 treated group administered AGE prior TiO2 by six hours at the same
      previously doses. All treatments were given orally every other day for two
      months. TiO2- intoxicated rats elicited a significant up-regulation in hepatic
      TLR-2, TLR-4, NF-KB/p65, CYP1B1 and CYP2B1 with pulmonary MMP-9, TIMP-1, TGF
      beta1, collagen-1alpha, fibronectin mRNA. Moreover, a significant elevation in
      serum AST, ALT, LDH, beta-glucuronidase, N-acetyl beta glucosaminidase,
      hydroxyproline, MMP-9, TIMP-1, fibronectin, TGF-beta1 levels with a significant
      decrease in total protein that ensued from TiO2 toxicity. The ultra
      histopathological findings reinforced these results. The co-administration of AGE
      and TiO2 alleviated these changes. These data support the nutraceutical role of
      AGE against TiO2 toxicity.

PMID- 27701052
TI  - The role of microRNAs in colorectal cancer.
AB  - Colorectal cancer (CRC) is still the third most common cancer in the world.
      Mechanism of CRC tumorigenesis has been widely studied at the molecular levels,
      and has been recently entered the area of microRNAs. MicroRNAs are small 19 to 22
      nucleotides of RNA that engage in the regulation of cell differentiation,
      apoptosis, and cell cycle progression. MicroRNAs are similar to small interfering
      RNA (siRNA), that post-transcriptionally regulate gene expression and control
      various cellular mechanisms. They are important factors in the carcinogenesis of
      CRC, one of the most important factors includes microRNA. MicroRNAs have been
      linked to CRC development, and these molecules have been recently studied as new
      potential biomarkers in diagnosis and treatment of CRC. Specific microRNA
      expression patterns help distinguish CRC from other colon related disease, and
      may be used as a prognostication factor in patients after treatment with
      different chemotherapy drugs. More over the newest molecular therapy via tumor
      suppressor micro RNA replacement can be new insight in molecular therapy of CRC.
      This review summarizes the potential roles of microRNAs as potential biomarkers
      for CRC diagnosis, and treatment.

PMID- 27701054
TI  - A novel electrochemical sensor based on Au@PANI composites film modified glassy
      carbon electrode binding molecular imprinting technique for the determination of
      melamine.
AB  - A novel molecularly imprinted electrochemical sensor for the rapid detection of
      melamine was reported in this paper. Glassy carbon electrode (GCE) was modified
      by Au and polyaniline composites (Au@PANI) deposited on the surface of GCE and
      were used to increase the electrode sensitivity and to amplify the sensor signal.
      Melamine template molecule was further assembled onto Au@PANI by the formation of
      hydrogen bonds, can implement the selective detection of melamine. This simple
      but efficient electrochemistry analysis platform presents a low detection limit
      of 1.39*10-6umolL-1 for detection of melamine, which is remarkably lower than the
      currently used methods and the previous reports. So, this method may open a new
      way for the determination of melamine which enables low cost, effective and
      sensitive determination. This shows the sensor can be potentially utilized for
      the detection of melamine in food, which allows the sensitive and selective
      determination of melamine from milk and feed.

PMID- 27701055
TI  - Reconstituting redox active centers of heme-containing proteins with
      biomineralized gold toward peroxidase mimics with strong intrinsic catalysis and
      electrocatalysis for H2O2 detection.
AB  - A facile and efficient enzymatic reconstitution methodology has been proposed for
      high-catalysis peroxidase mimics by remolding the redox active centers of heme
      containing proteins with the in-site biomineralized gold using hemoglobin (Hb) as
      a model. Catalytic hemin (Hem) was extracted from the active centers of Hb for
      the gold biomineralization and then reconstituted into apoHb to yield the Hem
      Au@apoHb nanocomposites showing dramatically improved intrinsic catalysis and
      electrocatalysis over natural Hb and Hem. The biomineralized gold, on the one
      hand, would act as "nanowires" to promote the electron transferring of the
      nanocomposites. On the other hand, it would create a reactivity pathway to pre
      organize and accumulate more substrates towards the active sites of the
      peroxidase mimics. Steady-state kinetics studies indicate that Hem-Au@apoHb could
      present much higher substrate affinity (lower Michaelis constants) and intrinsic
      catalysis even than some natural peroxidases. Moreover, the application
      feasibility of the prepared artificial enzymes was demonstrated by colorimetric
      assays and direct electrocatalysis for H2O2 sensing, showing a detection
      limitation low as 0.45MUM. Importantly, such a catalysis active-center
      reconstitution protocol may circumvent the substantial improvement of the
      intrinsic catalysis and electrocatalysis of diverse heme-containing proteins or
      enyzmes toward the extensive applications in the chemical, enviromental, and
      biomedical catalysis fields.

PMID- 27701057
TI  - Effect of metformin on global gene expression in liver of KKAy mice.
AB  - BACKGROUND: Metformin is a first-line drug for treating type 2 diabetes mellitus,
      yet its mechanism remains only partially understood and controversial. In this
      study we assessed a global gene expression profiling in liver of KKAy mice
      affected by metformin. This study aimed to identify the novel anti-diabetic
      mechanisms of metformin. METHODS: After KKAy mice were administered metformin for
      5 weeks, the gene changes profile in the livers of KKAy mice were assessed by
      using the Agilent whole mice genome oligo microarray. RESULTS: Metformin altered
      the gene expression profiles in liver of KKAy mice. To our best knowledge, some
      genes have not been reported until now, such as Anxa2, Atf6, and so on. These
      genes were involved in many pathways, such as peroxisome proliferator activated
      receptor signaling pathway. CONCLUSIONS: Gene expression changes induced by
      metformin were in support of the improvement of glucolipid metabolism and insulin
      resistance in KKAy mice. These findings expanded our knowledge of pharmacological
      action of metformin, and provided the potential novel insights and interesting
      information about the molecules involved in the antidiabetic effects of
      metformin.

PMID- 27701056
TI  - Nebivolol suppresses asymmetric dimethylarginine and attenuates cyclosporine
      induced nephrotoxicity and endothelial dysfunction in rats.
AB  - BACKGROUND: Cyclosporine A (CsA)-induced nephrotoxicity is a challenging problem
      complicating its chronic use in a large array of autoimmune diseases, as well as
      in organ transplantation. A considerable body of evidence points to the
      involvement of nitric oxide (NO) and its endogenous synthesis inhibitor,
      asymmetric dimethylarginine (ADMA), in CsA-induced renal and cardiovascular
      adverse effects. In this study, the potential of the third generation beta
      blocker, nebivolol, to modify the NO/ADMA system is hypothesized to play a role
      in protection against CsA-induced renal injury and endothelial dysfunction.
      METHODS: Both in vivo and in vitro studies were carried out on 36 male Wistar
      rats randomly divided into three groups; normal control, CsA (30mg/kg/day)
      treated or CsA+nebivolol (30mg/kg and 1mg/kg daily, respectively)-treated groups.
      After four weeks, blood pressure, lipid profile, renal functions, renal oxidative
      status, NO, inducible NO synthase and ADMA were assessed. In vitro evaluation of
      vascular relaxant responses of norepinephrine pre-contracted aortic rings to
      acetylcholine (ACh) and sodium nitroprusside were evaluated. RESULTS: Concurrent
      nebivolol treatment significantly attenuated CsA-induced hypertension, impairment
      of renal functions, oxidative stress and restored the balance in renal NO system
      with lowering of the elevated ADMA. This was associated with favourable effects
      on lipid profile. Nebivolol treatment also abrogated the CsA-induced impairment
      of relaxant responses of aortic rings to ACh. CONCLUSIONS: Nebivolol possesses
      multifaceted actions that make it advantageous to combat the CsA-induced toxic
      effects on renal and endothelial functions.

PMID- 27701053
TI  - MicroRNA-related polymorphisms and non-Hodgkin lymphoma susceptibility in the
      Multicenter AIDS Cohort Study.
AB  - BACKGROUND: MicroRNAs, small non-coding RNAs involved in gene regulation, are
      implicated in lymphomagenesis. We evaluated whether genetic variations in
      microRNA coding regions, binding sites, or biogenesis genes (collectively
      referred to as miRNA-SNPs) were associated with risk of AIDS-associated non
      Hodgkin lymphoma (AIDS-NHL), and serum levels of four lymphoma-related microRNAs.
      METHODS: Twenty-five miRNA-SNPs were genotyped in 180 AIDS-NHL cases and 529 HIV
      infected matched controls from the Multicenter AIDS Cohort Study (MACS), and real
      time polymerase chain reaction was used to quantify serum microRNA levels.
      Adjusted odds ratios (ORs) estimated using conditional logistic regression
      evaluated associations between miRNA-SNPs and AIDS-NHL risk. A semi-Bayes
      shrinkage approach was employed to reduce likelihood of false-positive
      associations. Adjusted mean ratios (MR) calculated using linear regression
      assessed associations between miRNA-SNPs and serum microRNA levels. RESULTS:
      DDX20 rs197412, a non-synonymous miRNA biogenesis gene SNP, was associated with
      AIDS-NHL risk (OR=1.34 per minor allele; 95% CI: 1.02-1.75), and higher miRNA-222
      serum levels nearing statistical significance (MR=1.21 per minor allele; 95% CI:
      0.98-1.49). MiRNA-196a2 rs11614913 was associated with decreased central nervous
      system (CNS) AIDS-NHL (CT vs. CC OR=0.52; 95% CI: 0.27-0.99). The minor allele of
      HIF1A rs2057482, which creates a miRNA-196a2 binding site, was associated with
      systemic AIDS-NHL risk (OR=1.73 per minor allele; 95% CI: 1.12-2.67), and
      decreased CNS AIDS-NHL risk (OR=0.49 per minor allele; 95% CI: 0.25-0.94).
      CONCLUSIONS: This study suggests that a few miRNA-SNPs are associated with AIDS
      NHL risk and may modulate miRNA expression. These results support a role for
      miRNA in AIDS-NHL and may highlight pathways to be targeted for risk
      stratification or therapeutics.

PMID- 27701058
TI  - Does valproate therapy in epileptic patients contribute to changing
      atherosclerosis risk factors? The role of lipids and free fatty acids.
AB  - BACKGROUND: We aimed to demonstrate the relationship between the valproate (VPA)
      treatment versus lipid and serum free fatty acids (FFAs) profiles to be the
      potential atherosclerosis risk factor in epileptic patients. METHODS: Fasting
      blood samples were taken from 21 adult VPA-treated patients and 21 controls. The
      profiles of lipids, FFAs, clinical parameters and body mass index (BMI) were
      evaluated. RESULTS: No significant differences between the study group and
      controls were found for any of the studied parameters. However, significant
      differences in the total cholesterol (CHOL), low-density-lipoprotein cholesterol
      (LDL), triglycerides, the CHOL/HDL (high-density-lipoprotein cholesterol) ratio,
      and Atherogenic Index of Plasma were observed for overweight patients when
      compared to those of normal weight. Patients with uncontrolled epilepsy tended to
      have significantly lower palmitic acid level than seizure-free patients. Oleic
      acid was found to be positively correlated with VPA concentration for patients
      with uncontrolled epilepsy, and with the dose corrected VPA concentration for all
      the patients. The acid was however negatively correlated with stearic acid for
      both the controls and the patients with uncontrolled epilepsy. PLS method
      revealed CHOL, LDL, triglycerides and myristic acid to be positively interrelated
      for the whole group under the study, whereas these parameters were found to be
      negatively correlated with VPA concentration, and positively with BMI.
      Furthermore, high sensitivity C-reactive protein was found to be negatively
      correlated with palmitic acid levels. CONCLUSION: Overweight VPA-treated patients
      are exposed to higher risk of atherosclerosis. Alterations in FFAs are likely to
      depend on seizures control, and on VPA levels.

PMID- 27701059
TI  - Exploring hazards of acute exposure of Acephate in Drosophila melanogaster and
      search for l-ascorbic acid mediated defense in it.
AB  - This study reveals protective role of l-ascorbic acid (25, 50 and 100MUg/mL)
      against toxic impacts of acute sub-lethal exposure of Acephate (5MUg/mL) in a non
      target organism Drosophila melanogaster. Organismal effect was evident from
      increased impairment in climbing activities (9 folds) of treated individuals who
      also manifested altered ocular architecture. These anomalies were reduced with l
      ascorbic acid (l-AA) supplementation. Acephate induced apoptotic lesions in eye
      imaginal discs and gut confirmed tissue damage that also reduced with l-AA co
      treatment. Reduction in viability of fat body cells (~41%), neural cells (~42%)
      and hemocytes (3 folds) indicates cytotoxic and immunotoxic potential of
      Acephate, which were significantly mitigated with l-AA co-administration. The sub
      cellular toxic impacts of Acephate treatment became obvious from enhancement in
      activities of antioxidant enzymes (CAT by ~1.63 folds, SOD by ~1.32 folds),
      detoxifying enzymes (Cyp450 by ~1.99 folds and GST by ~1.34 folds), 2.1 times
      boost in HSP 70 expression, and inhibition of cholinesterase activity (by ~0.66
      folds). DNA breaks evident through comet assay confirmed Acephate triggered
      genotoxicity which could also be prevented through co-administration of. L-AA
      Furthermore, the study proposes the use of Drosophila as a model to screen
      chemicals for their protective potential against pesticide toxicity.

PMID- 27701060
TI  - Zeolitic imidazolate framework-8 derived nanoporous carbon as an effective and
      recyclable adsorbent for removal of ciprofloxacin antibiotics from water.
AB  - The nanoporous carbons (NPC) derived from a one-step carbonization of zeolitic
      imidazolate framework-8 (ZIF-8) were synthesized and used for ciprofloxacin (CIP)
      removal from water. The resultant products were characterized by SEM, TEM, FT-IR,
      Raman, N2 adsorption-desorption analysis, XRD, TGA and Zeta potential. The
      optimized NPC-700 (carbonized at 700 degrees C for 2h) exhibited an optimal
      performance in CIP adsorption removal. CIP adsorption on NPC-700 as a function of
      contact time, initial CIP concentration, adsorbent dosage, pH, ionic strength and
      humic acid concentration were investigated. Kinetics of CIP removal was found to
      follow pseudo-second-order rate equation. Both Langmuir and Freundlich models
      fitted the adsorption data well and gave similar correlation coefficients
      (>0.96). However, Freundlich isotherm gave a better fit (r2=0.9969), suggesting a
      multilayer adsorption of CIP onto surface of NPC-700 adsorbent. The maximum
      adsorption capacity for CIP based on Langmuir model was 416.7mg/g, which was
      higher than those of other adsorbents. The NPC-700 material showed no apparent
      loss in CIP adsorption after seven cycles. These features reveal that the metal
      organic framework (MOF) derived NPC may be a promising adsorbent for CIP removal
      from water.

PMID- 27701061
TI  - Long-term stability of FeSO4 and H2SO4 treated chromite ore processing residue
      (COPR): Importance of H+ and SO42.
AB  - In this study, the long-term stability of Cr(VI) in the FeSO4 and H2SO4 (FeSO4
      H2SO4) treated chromite ore processing residue (COPR) after 400 curing days and
      the stabilization mechanisms were investigated. FeSO4-H2SO4 treatment
      significantly reduced toxicity characteristic leaching procedure (TCLP) and
      synthetic precipitation leaching procedure (SPLP) Cr(VI) concentrations to lower
      than the regulatory limit of 1.5mgL-1 (HJ/T 301-2007, China EPA) even for the
      samples curing 400days, achieving an outstanding long-term stability. Our
      independent leaching tests revealed that H+ and SO42- have synergistic effect on
      promoting the release of Cr(VI), which would make Cr(VI) easier accessed by
      Fe(II) during stabilization. The contributions of H+ and SO42- to Cr(VI) release
      ratio were 25%-44% and 19%-38%, respectively, as 5mol H2SO4 per kg COPR was used.
      X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and
      alkaline digestion analyses were also employed to interpret the possible
      stabilization mechanism. Cr(VI) released from COPR solid was reduced to Cr(III)
      by Fe(II), and then formed stable FexCr(1-x)(OH)3 precipitate. This study
      provides a facile and reliable scheme for COPR stabilization, and verifies the
      excellent long-term stability of the FeSO4-H2SO4 treated COPR.

PMID- 27701062
TI  - Therapeutic strategy for efficient reduction of serum uric acid levels with
      allopurinol versus benzbromarone in hyperuricemic patients with essential
      hypertension - A randomized crossover study (terao study).

PMID- 27701063
TI  - Physiological and sensory consequences of exercise oscillatory ventilation in
      heart failure-COPD.
AB  - BACKGROUND: Exercise oscillatory ventilation (EOV) is associated with poor
      ventilatory efficiency and higher operating lung volumes in heart failure. These
      abnormalities may be particularly deleterious to dyspnea and exercise tolerance
      in mechanically-limited patients, e.g. those with coexistent COPD. METHODS:
      Ventilatory, gas exchange and sensory responses to incremental exercise were
      contrasted in 68 heart failure-COPD patients (12 EOV+). EOV was established by
      standard criteria. RESULTS: Compared to EOV-, EOV+ had lower exercise capacity,
      worse ventilatory inefficiency and higher peak dyspnea scores (p<0.05). Peak
      capillary PCO2 (PcCO2) was higher and end-tidal CO2 (PETCO2) was lower in EOV+.
      Thus, greater (i.e., more positive) P(c-ET)CO2 and dead space/tidal volume values
      were found in these patients compared to EOV- (p<0.05). Ventilatory inefficiency
      was related to increased dead space/tidal volume in EOV+ (r=0.74; p<0.01). Owing
      to higher operating lung volumes, inspiratory reserve volume (IRV) decreased to a
      greater extent in EOV+. Tidal volume oscillations consistently ceased when a
      "critical" IRV was reached (~0.3-0.5L); thereafter, PcCO2 stabilized or increased
      and dyspnea scores rose sharply. Exercise capacity was closely related to IRV
      decrements and peak dyspnea in EOV+ (r=-0.78 and 0.84, respectively; p<0.01).
      CONCLUSIONS: Dyspnea and exercise tolerance are negatively influenced by EOV in
      heart failure patients presenting with COPD as co-morbidity. Pharmacological and
      non-pharmacological interventions known to decrease EOV might prove particularly
      valuable to mitigate symptom burden and exercise intolerance in this specific
      heart failure group.

PMID- 27701065
TI  - Informing Estimates of Program Effects for Studies of Mathematics Professional
      Development Using Teacher Content Knowledge Outcomes.
AB  - Mathematics professional development is widely offered, typically with the goal
      of improving teachers' content knowledge, the quality of teaching, and ultimately
      students' achievement. Recently, new assessments focused on mathematical
      knowledge for teaching (MKT) have been developed to assist in the evaluation and
      improvement of mathematics professional development. This study presents
      empirical estimates of average program change in MKT and its variation with the
      goal of supporting the design of experimental trials that are adequately powered
      to detect a specified program effect. The study drew on a large database
      representing five different assessments of MKT and collectively 326 professional
      development programs and 9,365 teachers. Results from cross-classified
      hierarchical growth models found that standardized average change estimates
      across the five assessments ranged from a low of 0.16 standard deviations (SDs)
      to a high of 0.26 SDs. Power analyses using the estimated pre- and posttest
      change estimates indicated that hundreds of teachers are needed to detect changes
      in knowledge at the lower end of the distribution. Even studies powered to detect
      effects at the higher end of the distribution will require substantial resources
      to conduct rigorous experimental trials. Empirical benchmarks that describe
      average program change and its variation provide a useful preliminary resource
      for interpreting the relative magnitude of effect sizes associated with
      professional development programs and for designing adequately powered trials.

PMID- 27701064
TI  - Overcoming Addictions, a Web-Based Application, and SMART Recovery, an Online and
      In-Person Mutual Help Group for Problem Drinkers, Part 2: Six-Month Outcomes of a
      Randomized Controlled Trial and Qualitative Feedback From Participants.
AB  - BACKGROUND: Despite empirical evidence supporting the use of Web-based
      interventions for problem drinking, much remains unknown about factors that
      influence their effectiveness. OBJECTIVE: We evaluated the performance of 2
      resources for people who want to achieve and maintain abstinence: SMART Recovery
      (SR) and Overcoming Addictions (OA). OA is a Web application based on SR. We also
      examined participant and intervention-related factors hypothesized to impact
      clinical outcomes of Web-based interventions. METHODS: We recruited 189 heavy
      drinkers through SR's website and in-person meetings throughout the United
      States. We began by randomly assigning participants to (1) SR meetings alone, (2)
      OA alone, and (3) OA and SR (OA+SR). Recruitment challenges compelled us to
      assign participants only to SR (n=86) or OA+SR (n=102). The experimental
      hypotheses were as follows: (1) Both groups will reduce their drinking and
      alcohol-related consequences at follow-up compared with their baseline levels,
      and (2) The OA+SR condition will reduce their drinking and alcohol or drug
      related consequences more than the SR only condition. Additionally, we derived 3
      groups empirically (SR, OA, and OA+SR) based on the participants' actual use of
      each intervention and conducted analyses by comparing them. Primary outcome
      measures included percent days abstinent (PDA), mean drinks per drinking day
      (DDD), and alcohol or drug-related consequences. Postbaseline assessments were
      conducted by phone at 3 and 6 months. Secondary analyses explored whether
      clinical issues (eg, severity of alcohol problems, level of distress, readiness
      to change) or intervention-related factors (eg, Internet fluency, satisfaction
      with site) affected outcomes. RESULTS: Both intent-to-treat analyses and the
      actual-use analyses showed highly significant improvement from baseline to follow
      ups for all 3 groups. Mean within-subject effect sizes were large (d>0.8)
      overall. There was no significant difference between groups in the amount of
      improvement from baseline to the average of the follow-ups. We found that
      participants who stopped drinking before joining the clinical trial had
      significantly better outcomes than participants who were still drinking when they
      joined the study. Neither Internet fluency nor participants' reported ease of
      navigating the site had an impact on outcomes. CONCLUSIONS: These results support
      our first experimental hypothesis but not the second. On average, participants
      improved on all dependent measures. Both SR and OA helped participants recover
      from their problem drinking. Web-based interventions can help even those
      individuals with lengthy histories of heavy drinking to make clinically
      significant reductions in their consumption and related problems. These
      interventions work well for individuals in the action stage of change. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01389297;
      https://clinicaltrials.gov/ct2/show/NCT01389297 (Archived by WebCite at
      http://www.webcitation.org/6kLNUNDcc).

PMID- 27701066
TI  - Ferritin and iron studies in anaemia and chronic disease.
AB  - Anaemia is a condition in which the number of red cells necessary to meet the
      body's physiological requirements is insufficient. Iron deficiency anaemia and
      the anaemia of chronic disease are the two most common causes of anaemia
      worldwide;1 iron homeostasis plays a pivotal role in the pathogenesis of both
      diseases. An understanding of how iron studies can be used to distinguish between
      these diseases is therefore essential not only for diagnosis but also in guiding
      management. This review will primarily focus on iron deficiency anaemia and
      anaemia of chronic disease; however, iron overload in anaemia will also be
      briefly discussed.

PMID- 27701067
TI  - Recommendation on testing for dihydropyrimidine dehydrogenase deficiency in the
      ESMO consensus guidelines for the management of patients with metastatic
      colorectal cancer.

PMID- 27701070
TI  - ESMO consensus conference on malignant lymphoma: general perspectives and
      recommendations for prognostic tools in mature B-cell lymphomas and chronic
      lymphocytic leukaemia.
AB  - The European Society for Medical Oncology (ESMO) consensus conference on mature B
      cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015
      in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading
      experts. The aim of the conference was to develop recommendations on critical
      subjects difficult to consider in detail in the ESMO Clinical Practice
      Guidelines. The following areas were identified: (i) the elderly patient, (ii)
      prognostic factors suitable for clinical use and (iii) the 'ultra-high-risk'
      group. Before the conference, the expert panel was divided into three working
      groups; each group focused on one of these areas in order to address four
      clinically relevant questions relating to that topic. All relevant scientific
      literature, as identified by the experts, was reviewed in advance. During the
      consensus conference, each working group developed recommendations to address
      each of the four questions assigned to their group. These recommendations were
      then presented to the entire panel and a consensus was reached. This manuscript
      presents recommendations dedicated to the second area of interest, i.e.
      prognostic factors suitable for clinical use. The four topics [i.e. interim
      positron emission tomography (PET), TP53 mutations, cell of origin (COO) and
      minimal residual disease (MRD)] were primarily chosen because of the bulk of
      available data together with the lack of clear guidance regarding their use in
      clinical practice and within clinical trials. Results, including a summary of
      evidence supporting each recommendation, are detailed in this manuscript. The
      panel acknowledged that detection of TP53 inactivation by deletion or mutation in
      CLL should be implemented in clinical practice (level of evidence I, strength of
      recommendation A). Due to their potentially high prognostic value, at least in
      some lymphoma entities, implementation of interim PET, COO and MRD was highly
      recommended in the context of clinical trials. All expert panel members approved
      this final article.

PMID- 27701074
TI  - CeNDR, the Caenorhabditis elegans natural diversity resource.
AB  - Studies in model organisms have yielded considerable insights into the etiology
      of disease and our understanding of evolutionary processes. Caenorhabditis
      elegans is among the most powerful model organisms used to understand biology.
      However, C. elegans is not used as extensively as other model organisms to
      investigate how natural variation shapes traits, especially through the use of
      genome-wide association (GWA) analyses. Here, we introduce a new platform, the C.
      elegans Natural Diversity Resource (CeNDR) to enable statistical genetics and
      genomics studies of C. elegans and to connect the results to human disease. CeNDR
      provides the research community with wild strains, genome-wide sequence and
      variant data for every strain, and a GWA mapping portal for studying natural
      variation in C. elegans Additionally, researchers outside of the C. elegans
      community can benefit from public mappings and integrated tools for comparative
      analyses. CeNDR uses several databases that are continually updated through the
      addition of new strains, sequencing data, and association mapping results. The
      CeNDR data are accessible through a freely available web portal located at
      http://www.elegansvariation.org or through an application programming interface.

PMID- 27701075
TI  - A double-strand break can trigger immunoglobulin gene conversion.
AB  - All three B cell-specific activities of the immunoglobulin (Ig) gene re-modeling
      system-gene conversion, somatic hypermutation and class switch recombination
      require activation-induced deaminase (AID). AID-induced DNA lesions must be
      further processed and dissected into different DNA recombination pathways. In
      order to characterize potential intermediates for Ig gene conversion, we inserted
      an I-SceI recognition site into the complementarity determining region 1 (CDR1)
      of the Ig light chain locus of the AID knockout DT40 cell line, and conditionally
      expressed I-SceI endonuclease. Here, we show that a double-strand break (DSB) in
      CDR1 is sufficient to trigger Ig gene conversion in the absence of AID. The
      pattern and pseudogene usage of DSB-induced gene conversion were comparable to
      those of AID-induced gene conversion; surprisingly, sometimes a single DSB
      induced multiple gene conversion events. These constitute direct evidence that a
      DSB in the V region can be an intermediate for gene conversion. The fate of the
      DNA lesion downstream of a DSB had more flexibility than that of AID, suggesting
      two alternative models: (i) DSBs during the physiological gene conversion are in
      the minority compared to single-strand breaks (SSBs), which are frequently
      generated following DNA deamination, or (ii) the physiological gene conversion is
      mediated by a tightly regulated DSB that is locally protected from non-homologous
      end joining (NHEJ) or other non-homologous DNA recombination machineries.

PMID- 27701077
TI  - Evaluation and improvement of a single nucleotide polymorphism-based PCR assay
      for rapid differentiation of live attenuated vaccine strains from field isolates
      of Erysipelothrix rhusiopathiae.
AB  - A single nucleotide polymorphism-based PCR assay has been developed to
      differentiate the attenuated vaccine strain used in Japan from field isolates of
      Erysipelothrix rhusiopathiae found in pigs. However, this assay has been
      evaluated with only Japanese strains and isolates; therefore, it is unknown
      whether it could be used in other countries with E. rhusiopathiae strains and
      isolates of different genetic backgrounds. In our study, the PCR assay was
      evaluated using Chinese E. rhusiopathiae vaccine strains and field isolates. The
      PCR assay was able to differentiate the attenuated vaccine strains from the field
      isolates of E. rhusiopathiae in China but with a pattern different from that
      observed in Japan (only a single nucleotide polymorphism was detected in the
      Chinese vaccine strains compared with 5 in the Japanese vaccine strains).
      Importantly, either a DNA polymerase without 3' to 5' exonuclease activity or an
      exo+ polymerase with an antibody inhibiting the proofreading activity was
      required. In conclusion, after evaluation and improvement, this fast
      differentiation assay can be extended from Japan to China.

PMID- 27701078
TI  - Spontaneous reproductive pathology in female guinea pigs.
AB  - Reproductive pathology of domestic guinea pigs is underreported to date. To
      provide a comprehensive review of uterine disease in guinea pigs, we performed a
      retrospective study of the pathology archives of the University of Tennessee,
      College of Veterinary Medicine. By histology, 13 of 37 uterine lesions in 23
      animals were neoplastic; the other 24 nonneoplastic lesions included cystic
      endometrial hyperplasia (16 of 24), endometrial hemorrhage (3 of 24), pyometra (2
      of 24), polyp (2 of 24), and mucometra (1 of 24). The most common guinea pig
      uterine neoplasms were uterine leiomyomas (6 of 13), followed by adenomas (3 of
      13) and leiomyosarcomas (1 of 13). Other neoplasms included anaplastic tumors of
      unknown origin (2 of 13) and choriocarcinoma (1 of 13). Both anaplastic tumors
      and the choriocarcinoma were positive for vimentin. The choriocarcinoma was
      positive for HSD83B1, indicating a trophoblastic origin and its final diagnosis.
      All were negative for cytokeratin and smooth muscle. In multiple animals, more
      than 1 tumor or lesion was reported. Estrogen receptor and progesterone receptor
      expression was nearly 100% in uterine neoplasms. Nearly all animals for which
      data were available had cystic rete ovarii (18 of 19); the animal with no cystic
      rete ovarii had paraovarian cysts. In our study, female pet guinea pigs had a
      tendency to develop cystic endometrial hyperplasia and uterine neoplasia. Factors
      for the development of these lesions could be cystic rete ovarii, hormone
      dysregulation, and/or age. Other factors could contribute to the development of
      uterine lesions. As in other species, early ovariohysterectomy could decrease the
      prevalence of uterine lesions.

PMID- 27701076
TI  - Laboratory evolution of artificially expanded DNA gives redesignable aptamers
      that target the toxic form of anthrax protective antigen.
AB  - Reported here is a laboratory in vitro evolution (LIVE) experiment based on an
      artificially expanded genetic information system (AEGIS). This experiment
      delivers the first example of an AEGIS aptamer that binds to an isolated protein
      target, the first whose structural contact with its target has been outlined and
      the first to inhibit biologically important activities of its target, the
      protective antigen from Bacillus anthracis We show how rational design based on
      secondary structure predictions can also direct the use of AEGIS to improve the
      stability and binding of the aptamer to its target. The final aptamer has a
      dissociation constant of ~35 nM. These results illustrate the value of AEGIS-LIVE
      for those seeking to obtain receptors and ligands without the complexities of
      medicinal chemistry, and also challenge the biophysical community to develop new
      tools to analyze the spectroscopic signatures of new DNA folds that will emerge
      in synthetic genetic systems replacing standard DNA and RNA as platforms for
      LIVE.

PMID- 27701079
TI  - Heart Failure Therapy in 2016: SHIFTing the PARADIGM From Antiquated Therapies
      Toward Novel Agents.
AB  - Heart failure (HF) continues to afflict millions of Americans, resulting in
      substantial clinical and economic burden to our society. Recent literature has
      highlighted the role of 2 novel therapies (an angiotensin receptor
      blocker/neprilysin inhibitor and ivabradine) in further reducing residual disease
      in HF. Simultaneously, evidence has mounted suggesting that older therapies like
      digoxin are not effective in contemporary practice and, in fact, may be harmful.
      This editorial summarizes the most recently published articles pertaining to both
      new and old HF therapies and provides a call to action to pharmacists on how to
      shift patients toward effective drug regimens.

PMID- 27701080
TI  - Cobimetinib.
AB  - OBJECTIVE: To review and summarize data on cobimetinib, which was approved by the
      US Food and Drug Administration (FDA) in November 2015 for use in combination
      with vemurafenib for unresectable or metastatic melanoma with a BRAFV600E or
      V600K mutation. DATA SOURCES: A literature search using PubMed was conducted
      using the terms cobimetinib, MEK inhibitor, and melanoma from January 2000 to
      June 2016. STUDY SELECTION AND DATA EXTRACTION: The literature search was
      confined to human studies published in English. Trials of cobimetinib for
      melanoma were prioritized. DATA SYNTHESIS: Cobimetinib is a reversible inhibitor
      of MEK1 and MEK2. Its FDA approval was based on a phase III, randomized trial of
      vemurafenib monotherapy (n = 248) or vemurafenib and cobimetinib (n = 247) in
      unresectable stage IIIC or IV melanoma with a BRAFV600 mutation. Cobimetinib was
      administered as 60 mg orally daily for 21 days/7 days off, whereas vemurafenib
      was administered as 960 mg twice daily. Vemurafenib and cobimetinib were
      associated with an objective response rate of 68%, and median progression-free
      survival of 9.9 months. The overall survival was not reached at the time of first
      interim analysis. Clinically relevant grade >=3 adverse events were diarrhea
      (6%), rash (6%), photosensitivity (2%), elevated liver function tests (LFTs) (8%
      12%), increased creatine kinase (11%), and retinal detachment (3%). CONCLUSION:
      Cobimetinib combined with vemurafenib is an alternative BRAF/MEK inhibitor
      therapy for unresectable or metastatic melanoma with BRAFV600 mutation. The role
      of cobimetinib in melanoma and other solid tumors is likely to expand as the
      results from ongoing studies become available.

PMID- 27701082
TI  - The Predictive Role of Maternal Parenting and Stress on Pupils' Bullying
      involvement.
AB  - The link between inappropriate parenting style and both bullying and
      victimization is well documented. However, it is not clear as to which kind of
      parenting style is associated with victimization. Furthermore, no studies have
      yet been conducted regarding the role of parental stress in bullying and
      victimization. This study aimed to examine the role of parenting styles and
      maternal stress in pupils' bullying and victimization. A total of 300 primary
      school pupils, enrolled in fourth and fifth grades, participated in the study.
      Initially, 100 noninvolved pupils were randomly selected using a multistage
      cluster sampling method. Then using a screening method, 100 bully pupils and 100
      victimized peers were selected. Olweus Bullying Scale and teacher nomination were
      administered for screening these pupils. Baumrind Parenting Style Questionnaire
      and revised version of Abidin Parental Stress Index (short form) were also
      applied to all pupils in the study. Data were analyzed using discriminant
      function analysis. The findings showed that (a) with regard to parenting styles,
      significant differences were found among groups. Authoritarian parenting style
      could significantly predict pupils' bullying behavior, whereas victimization was
      predictable in families with permissive parenting style. In addition, noninvolved
      pupils were predicted to have authoritative parenting style. (b) Considering
      maternal stress, significant differences were observed across groups. Parents of
      bullies and victims were predicted to have higher maternal stress than
      noninvolved pupils. The implications of the study in relation to the role of
      mothers in bullying and victimization are discussed.

PMID- 27701081
TI  - Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory
      Drugs, Penicillins, and Proton Pump Inhibitors.
AB  - OBJECTIVE: To review the potential drug interactions between low-dose
      methotrexate (LD-MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs),
      penicillins, and proton-pump inhibitors (PPIs) given the disparity between
      interactions reported for high-dose and low-dose MTX to help guide clinicians.
      DATA SOURCES: A literature search was performed in MEDLINE (1946 to September
      2016), EMBASE (1974 to September 2016), and International Pharmaceutical
      Abstracts (1970 to January 2015) to identify reports describing potential drug
      interactions between LD-MTX and NSAIDS, penicillins, or PPIs. Reference lists of
      included articles were reviewed to find additional eligible articles. STUDY
      SELECTION AND DATA EXTRACTION: All English-language observational, randomized,
      and pharmacokinetic (PK) studies assessing LD-MTX interactions in humans were
      analyzed to determine clinical relevance in making recommendations to clinicians.
      Clinical case reports were assigned a Drug Interaction Probability Scale score.
      DATA SYNTHESIS: A total of 32 articles were included (28 with NSAIDs, 3 with
      penicillins, and 2 with PPIs [1 including both PPI and NSAID]). Although there
      are some PK data to describe increased LD-MTX concentrations when NSAIDs are used
      concomitantly, the clinical relevance remains unclear. Based on the limited data
      on LD-MTX with penicillins and PPIs, no clinically meaningful interaction was
      identified. CONCLUSION: Given the available evidence, the clinical importance of
      the interaction between LD-MTX and NSAIDs, penicillins, and PPIs cannot be
      substantiated. Health care providers should assess the benefit and risk of LD-MTX
      regardless of concomitant drug use, including factors known to predispose
      patients to MTX toxicity, and continue to monitor clinical and laboratory
      parameters per guideline recommendations.

PMID- 27701083
TI  - Reactive Protection? Fear, Victimization, and Fighting Among U.S. High School
      Students.
AB  - Youth violence in high schools is a pervasive and persistent problem in the
      United States. Students engage in physical fights, experience bullying and teen
      dating violence (TDV), are threatened with weapons, and miss school due to safety
      concerns. However, despite theoretical support, research has not sufficiently
      addressed the relationship between students' fear and fighting at school. This
      secondary analysis used data from the 2013 Youth Risk Behavior Survey ( n =
      13,583) to examine the relationship between fear at school, victimization, and
      engagement in fighting at school among high school students. We created a 3-item
      composite fear variable, conducted logistic regression to examine likelihood of
      fighting, and multinomial regression to examine risk for multiple fights, and
      stratified all models by gender. Findings indicate that both male and female
      students who experienced fear were more likely to engage in fights at school than
      peers who did not experience fear, even when controlling for other factors.
      Likewise, the more fear incidents a student experienced, the more at risk they
      were for engaging in multiple fights. Findings on victimization indicate that the
      relationship with fighting is more straightforward for male students than for
      female students. For males, being bullied and experiencing multiple incidents of
      physical and sexual TDV were all associated with fighting at school. For females,
      however, only one type of victimization was associated with fighting at school:
      experiencing multiple incidents of physical TDV. Overall, findings suggest that
      fear may be more than merely a by-product of fighting, but rather-as the extant
      research supports-fear also can be generalized across situations and displayed
      through patterns of aggression. Findings support the need for interventions aimed
      at skill-building in areas of communication, emotion regulation, conflict
      resolution, and healthy relationships to help youth-particularly those in younger
      grades-negotiate interpersonal relationships without the use of violence.

PMID- 27701084
TI  - Factor VII Deficiency: From Basics to Clinical Laboratory Diagnosis and Patient
      Management.
AB  - Factor VII (FVII) deficiency is a rare inheritable bleeding disorder affecting
      1/500 000 individuals. Clinical manifestations are heterogeneous, from
      asymptomatic to severe and potentially fatal bleeding. These clinical
      manifestations do not correlate well with FVII plasma levels. For this reason,
      FVII-deficient patient management during surgery or for long-term prophylaxis
      remains challenging. Laboratory testing for FVII activity is, however, the first
      line method for FVII deficiency diagnosis and is helpful for managing patients in
      combination with clinical history. Additional testing consists of FVII
      immunoassay and genetic testing. Genetic abnormalities on the FVII gene are
      heterogeneous and can translate into quantitative or qualitative defects. Some of
      the latter can react differently with different thromboplastins; this can be
      misleading for the laboratory as no consensus exists at present on an FVII
      deficiency diagnosis methodology. Indeed, no single test is able to predict
      accurately the bleeding risk. This review provides a broad picture of inherited
      and acquired FVII deficiency with a particular focus on laboratory diagnosis.

PMID- 27701085
TI  - Detection of local H2O exposed at the surface of Ceres.
AB  - The surface of dwarf planet Ceres contains hydroxyl-rich materials. Theories
      predict a water ice-rich mantle, and water vapor emissions have been observed,
      yet no water (H2O) has been previously identified. The Visible and InfraRed (VIR)
      mapping spectrometer onboard the Dawn spacecraft has now detected water
      absorption features within a low-illumination, highly reflective zone in Oxo, a
      10-kilometer, geologically fresh crater, on five occasions over a period of 1
      month. Candidate materials are H2O ice and mineral hydrates. Exposed H2O ice
      would become optically undetectable within tens of years under current Ceres
      temperatures; consequently, only a relatively recent exposure or formation of H2O
      would explain Dawn's findings. Some mineral hydrates are stable on geological
      time scales, but their formation would imply extended contact with ice or liquid
      H2O.

PMID- 27701086
TI  - Distribution of phyllosilicates on the surface of Ceres.
AB  - The dwarf planet Ceres is known to host phyllosilicate minerals at its surface,
      but their distribution and origin have not previously been determined. We used
      the spectrometer onboard the Dawn spacecraft to map their spatial distribution on
      the basis of diagnostic absorption features in the visible and near-infrared
      spectral range (0.25 to 5.0 micrometers). We found that magnesium- and ammonium
      bearing minerals are ubiquitous across the surface. Variations in the strength of
      the absorption features are spatially correlated and indicate considerable
      variability in the relative abundance of the phyllosilicates, although their
      composition is fairly uniform. These data, along with the distinctive spectral
      properties of Ceres relative to other asteroids and carbonaceous meteorites,
      indicate that the phyllosilicates were formed endogenously by a globally
      widespread and extensive alteration process.

PMID- 27701087
TI  - Cryovolcanism on Ceres.
AB  - Volcanic edifices are abundant on rocky bodies of the inner solar system. In the
      cold outer solar system, volcanism can occur on solid bodies with a water-ice
      shell, but derived cryovolcanic constructs have proved elusive. We report the
      discovery, using Dawn Framing Camera images, of a landform on dwarf planet Ceres
      that we argue represents a viscous cryovolcanic dome. Parent material of the
      cryomagma is a mixture of secondary minerals, including salts and water ice.
      Absolute model ages from impact craters reveal that extrusion of the dome has
      occurred recently. Ceres' evolution must have been able to sustain recent
      interior activity and associated surface expressions. We propose salts with low
      eutectic temperatures and thermal conductivities as key drivers for Ceres' long
      term internal evolution.

PMID- 27701090
TI  - Erratum for the Report "Large-scale magnetic fields at high Reynolds numbers in
      magnetohydrodynamic simulations" by H. Hotta, M. Rempel, T. Yokoyama.

PMID- 27701088
TI  - The geomorphology of Ceres.
AB  - Analysis of Dawn spacecraft Framing Camera image data allows evaluation of the
      topography and geomorphology of features on the surface of Ceres. The dwarf
      planet is dominated by numerous craters, but other features are also common.
      Linear structures include both those associated with impact craters and those
      that do not appear to have any correlation to an impact event. Abundant lobate
      flows are identified, and numerous domical features are found at a range of
      scales. Features suggestive of near-surface ice, cryomagmatism, and cryovolcanism
      have been identified. Although spectroscopic analysis has currently detected
      surface water ice at only one location on Ceres, the identification of these
      potentially ice-related features suggests that there may be at least some ice in
      localized regions in the crust.

PMID- 27701091
TI  - The science-policy interface.

PMID- 27701089
TI  - Cratering on Ceres: Implications for its crust and evolution.
AB  - Thermochemical models have predicted that Ceres, is to some extent,
      differentiated and should have an icy crust with few or no impact craters. We
      present observations by the Dawn spacecraft that reveal a heavily cratered
      surface, a heterogeneous crater distribution, and an apparent absence of large
      craters. The morphology of some impact craters is consistent with ice in the
      subsurface, which might have favored relaxation, yet large unrelaxed craters are
      also present. Numerous craters exhibit polygonal shapes, terraces, flowlike
      features, slumping, smooth deposits, and bright spots. Crater morphology and
      simple-to-complex crater transition diameters indicate that the crust of Ceres is
      neither purely icy nor rocky. By dating a smooth region associated with the
      Kerwan crater, we determined absolute model ages (AMAs) of 550 million and 720
      million years, depending on the applied chronology model.

PMID- 27701092
TI  - News at a glance.

PMID- 27701093
TI  - NASA to launch asteroid-sampling mission.

PMID- 27701094
TI  - London's biomedical behemoth opens its doors.

PMID- 27701096
TI  - Duke fraud case highlights financial risks for universities.

PMID- 27701095
TI  - A painstaking overhaul for cardiac safety testing.

PMID- 27701097
TI  - Congress faces a lengthy science to-do list.

PMID- 27701098
TI  - Mentoring's moment.

PMID- 27701099
TI  - Second chapter.

PMID- 27701100
TI  - Nanoporous fabrics could keep you cool.

PMID- 27701101
TI  - Tumors set time.

PMID- 27701102
TI  - Effects of a warming Arctic.

PMID- 27701103
TI  - Induced pluripotent stem cells, past and future.

PMID- 27701104
TI  - Coordinate efforts on EU invasive species.

PMID- 27701105
TI  - USGS scientists open to change.

PMID- 27701106
TI  - Rescued wildlife in China remains at risk.

PMID- 27701107
TI  - Dawn arrives at Ceres: Exploration of a small, volatile-rich world.
AB  - On 6 March 2015, Dawn arrived at Ceres to find a dark, desiccated surface
      punctuated by small, bright areas. Parts of Ceres' surface are heavily cratered,
      but the largest expected craters are absent. Ceres appears gravitationally
      relaxed at only the longest wavelengths, implying a mechanically strong
      lithosphere with a weaker deep interior. Ceres' dry exterior displays
      hydroxylated silicates, including ammoniated clays of endogenous origin. The
      possibility of abundant volatiles at depth is supported by geomorphologic
      features such as flat crater floors with pits, lobate flows of materials, and a
      singular mountain that appears to be an extrusive cryovolcanic dome. On one
      occasion, Ceres temporarily interacted with the solar wind, producing a bow shock
      accelerating electrons to energies of tens of kilovolts.

PMID- 27701108
TI  - A highly active and stable IrOx/SrIrO3 catalyst for the oxygen evolution
      reaction.
AB  - Oxygen electrochemistry plays a key role in renewable energy technologies such as
      fuel cells and electrolyzers, but the slow kinetics of the oxygen evolution
      reaction (OER) limit the performance and commercialization of such devices. Here
      we report an iridium oxide/strontium iridium oxide (IrOx/SrIrO3) catalyst formed
      during electrochemical testing by strontium leaching from surface layers of thin
      films of SrIrO3 This catalyst has demonstrated specific activity at 10 milliamps
      per square centimeter of oxide catalyst (OER current normalized to catalyst
      surface area), with only 270 to 290 millivolts of overpotential for 30 hours of
      continuous testing in acidic electrolyte. Density functional theory calculations
      suggest the formation of highly active surface layers during strontium leaching
      with IrO3 or anatase IrO2 motifs. The IrOx/SrIrO3 catalyst outperforms known IrOx
      and ruthenium oxide (RuOx) systems, the only other OER catalysts that have
      reasonable activity in acidic electrolyte.

PMID- 27701109
TI  - Enantioselective cyanation of benzylic C-H bonds via copper-catalyzed radical
      relay.
AB  - Direct methods for stereoselective functionalization of sp3-hybridized carbon
      hydrogen [C(sp3)-H] bonds in complex organic molecules could facilitate much more
      efficient preparation of therapeutics and agrochemicals. Here, we report a copper
      catalyzed radical relay pathway for enantioselective conversion of benzylic C-H
      bonds into benzylic nitriles. Hydrogen-atom abstraction affords an achiral
      benzylic radical that undergoes asymmetric C(sp3)-CN bond formation upon reaction
      with a chiral copper catalyst. The reactions proceed efficiently at room
      temperature with the benzylic substrate as limiting reagent, exhibit broad
      substrate scope with high enantioselectivity (typically 90 to 99% enantiomeric
      excess), and afford products that are key precursors to important bioactive
      molecules. Mechanistic studies provide evidence for diffusible organic radicals
      and highlight the difference between these reactions and C-H oxidations mediated
      by enzymes and other catalysts that operate via radical rebound pathways.

PMID- 27701110
TI  - Radiative human body cooling by nanoporous polyethylene textile.
AB  - Thermal management through personal heating and cooling is a strategy by which to
      expand indoor temperature setpoint range for large energy saving. We show that
      nanoporous polyethylene (nanoPE) is transparent to mid-infrared human body
      radiation but opaque to visible light because of the pore size distribution (50
      to 1000 nanometers). We processed the material to develop a textile that promotes
      effective radiative cooling while still having sufficient air permeability, water
      wicking rate, and mechanical strength for wearability. We developed a device to
      simulate skin temperature that shows temperatures 2.7 degrees  and 2.0 degrees C
      lower when covered with nanoPE cloth and with processed nanoPE cloth,
      respectively, than when covered with cotton. Our processed nanoPE is an effective
      and scalable textile for personal thermal management.

PMID- 27701112
TI  - Plant development regulated by cytokinin sinks.
AB  - Morphogenetic signals control the patterning of multicellular organisms.
      Cytokinins are mobile signals that are perceived by subsets of plant cells. We
      found that the responses to cytokinin signaling during Arabidopsis development
      are constrained by the transporter PURINE PERMEASE 14 (PUP14). In our
      experiments, the expression of PUP14 was inversely correlated to the cytokinin
      signaling readout. Loss of PUP14 function allowed ectopic cytokinin signaling
      accompanied by aberrant morphogenesis in embryos, roots, and the shoot apical
      meristem. PUP14 protein localized to the plasma membrane and imported bioactive
      cytokinins, thus depleting apoplastic cytokinin pools and inhibiting perception
      by plasma membrane-localized cytokinin sensors to create a sink for active
      ligands. We propose that the spatiotemporal cytokinin sink patterns established
      by PUP14 determine the cytokinin signaling landscape that shapes the
      morphogenesis of land plants.

PMID- 27701111
TI  - Ligand-accelerated enantioselective methylene C(sp3)-H bond activation.
AB  - Effective differentiation of prochiral carbon-hydrogen (C-H) bonds on a single
      methylene carbon via asymmetric metal insertion remains a challenge. Here, we
      report the discovery of chiral acetyl-protected aminoethyl quinoline ligands that
      enable asymmetric palladium insertion into prochiral C-H bonds on a single
      methylene carbon center. We apply these palladium complexes to catalytic
      enantioselective functionalization of beta-methylene C-H bonds in aliphatic
      amides. Using bidentate ligands to accelerate C-H activation of otherwise
      unreactive monodentate substrates is crucial for outcompeting the background
      reaction driven by substrate-directed cyclopalladation, thereby avoiding erosion
      of enantioselectivity. The potential of ligand acceleration in C-H activation is
      also demonstrated by enantioselective beta-C-H arylation of simple carboxylic
      acids without installing directing groups.

PMID- 27701113
TI  - Benefits and risks of the Sanofi-Pasteur dengue vaccine: Modeling optimal
      deployment.
AB  - The first approved dengue vaccine has now been licensed in six countries. We
      propose that this live attenuated vaccine acts like a silent natural infection in
      priming or boosting host immunity. A transmission dynamic model incorporating
      this hypothesis fits recent clinical trial data well and predicts that vaccine
      effectiveness depends strongly on the age group vaccinated and local transmission
      intensity. Vaccination in low-transmission settings may increase the incidence of
      more severe "secondary-like" infection and, thus, the numbers hospitalized for
      dengue. In moderate transmission settings, we predict positive impacts overall
      but increased risks of hospitalization with dengue disease for individuals who
      are vaccinated when seronegative. However, in high-transmission settings,
      vaccination benefits both the whole population and seronegative recipients. Our
      analysis can help inform policy-makers evaluating this and other candidate dengue
      vaccines.

PMID- 27701115
TI  - Thanks to the glass ceiling breakers.

PMID- 27701114
TI  - Instantaneous ion configurations in the K+ ion channel selectivity filter
      revealed by 2D IR spectroscopy.
AB  - Potassium channels are responsible for the selective permeation of K+ ions across
      cell membranes. K+ ions permeate in single file through the selectivity filter, a
      narrow pore lined by backbone carbonyls that compose four K+ binding sites. Here,
      we report on the two-dimensional infrared (2D IR) spectra of a semisynthetic KcsA
      channel with site-specific heavy (13C18O) isotope labels in the selectivity
      filter. The ultrafast time resolution of 2D IR spectroscopy provides an
      instantaneous snapshot of the multi-ion configurations and structural
      distributions that occur spontaneously in the filter. Two elongated features are
      resolved, revealing the statistical weighting of two structural conformations.
      The spectra are reproduced by molecular dynamics simulations of structures with
      water separating two K+ ions in the binding sites, ruling out configurations with
      ions occupying adjacent sites.

PMID- 27701116
TI  - Interlobar collateral ventilation in severe emphysema.

PMID- 27701117
TI  - Role of acid sphingomyelinase and IL-6 as mediators of endotoxin-induced
      pulmonary vascular dysfunction.
AB  - BACKGROUND: Pulmonary hypertension (PH) is frequently observed in patients with
      acute respiratory distress syndrome (ARDS) and it is associated with an increased
      risk of mortality. Both acid sphingomyelinase (aSMase) activity and interleukin 6
      (IL-6) levels are increased in patients with sepsis and correlate with worst
      outcomes, but their role in pulmonary vascular dysfunction pathogenesis has not
      yet been elucidated. Therefore, the aim of this study was to determine the
      potential contribution of aSMase and IL-6 in the pulmonary vascular dysfunction
      induced by lipopolysaccharide (LPS). METHODS: Rat or human pulmonary arteries
      (PAs) or their cultured smooth muscle cells (SMCs) were exposed to LPS, SMase or
      IL-6 in the absence or presence of a range of pharmacological inhibitors. The
      effects of aSMase inhibition in vivo with D609 on pulmonary arterial pressure and
      inflammation were assessed following intratracheal administration of LPS.
      RESULTS: LPS increased ceramide and IL-6 production in rat pulmonary artery
      smooth muscle cells (PASMCs) and inhibited pulmonary vasoconstriction induced by
      phenylephrine or hypoxia (HPV), induced endothelial dysfunction and potentiated
      the contractile responses to serotonin. Exogenous SMase and IL-6 mimicked the
      effects of LPS on endothelial dysfunction, HPV failure and hyperresponsiveness to
      serotonin in PA; whereas blockade of aSMase or IL-6 prevented LPS-induced
      effects. Finally, administration of the aSMase inhibitor D609 limited the
      development of endotoxin-induced PH and ventilation-perfusion mismatch. The
      protective effects of D609 were validated in isolated human PAs. CONCLUSIONS: Our
      data indicate that aSMase and IL-6 are not simply biomarkers of poor outcomes but
      pathogenic mediators of pulmonary vascular dysfunction in ARDS secondary to Gram
      negative infections.

PMID- 27701118
TI  - CTAS: a CT score to quantify disease activity in pulmonary sarcoidosis.
AB  - BACKGROUND: A major gap in the management of sarcoidosis is the lack of
      accessible and objective methods to measure disease activity. Since 90% of
      patients have pulmonary involvement, we explored if a disease activity score
      based on thoracic CT scans could address this clinical issue. METHODS: High
      resolution CT scans from 100 consecutive patients with sarcoidosis at a regional
      sarcoidosis service were scored for extent of CT abnormalities known to relate to
      granuloma or lymphocytic infiltration from published CT-pathological studies.
      These individual abnormality scores were then correlated against serum ACE, sIL
      2R and change in FVC to identify CT abnormalities that reflect contemporaneous
      disease activity. The sum of these scores, or CT Activity Score (CTAS), was then
      validated against FVC response to treatment. FINDINGS: CT extent scores for
      nodularity, ground-glass opacification, interlobular septal thickening and
      consolidation correlated significantly with at least one of the disease activity
      parameters and were used to form CTAS. CTAS was found to predict FVC response to
      treatment at 1 year and was highly reproducible between radiologists. An
      abbreviated CTAS (aCTAS), constructed from presence or absence of the four CT
      abnormalities, also showed significant correlation with FVC response to
      treatment. CTAS and aCTAS also correlated with response to treatment in the
      fibrotic subgroup. INTERPRETATION: CTAS provides a concept for an objective and
      reproducible CT scoring method to quantify disease activity in sarcoidosis. The
      score can potentially be used to stratify patients according to disease activity,
      determine response to treatment and establish if fibrotic sarcoidosis is active.

PMID- 27701119
TI  - Molecular Impact of Electronic Cigarette Aerosol Exposure in Human Bronchial
      Epithelium.
AB  - Little evidence is available regarding the physiological effects of exposure to
      electronic cigarette (ECIG) aerosol. We sought to determine the molecular impact
      of ECIG aerosol exposure in human bronchial epithelial cells (HBECs). Gene
      expression profiling was conducted in primary grown at air liquid interface and
      exposed to 1 of 4 different ECIG aerosols, traditional tobacco cigarette (TCIG)
      smoke, or clean air. Findings were validated experimentally with quantitative
      polymerase chain reaction and a reactive oxygen species immunoassay. Using gene
      set enrichment analysis, signatures of in vitro ECIG exposure were compared with
      those generated from bronchial epithelial brushings of current TCIG smokers and
      former TCIG smokers currently using ECIGs. We found 546 genes differentially
      expressed across the ECIG, TCIG, and air-exposed groups of HBECs (ANOVA; FDR q <
      .05; fold change > 1.5). A subset of these changes were shared between TCIG- and
      ECIG-exposed HBECs. ECIG exposure induced genes involved in oxidative and
      xenobiotic stress pathways and increased a marker of reactive oxygen species
      production in a dose-dependent manner. ECIG exposure decreased expression of
      genes involved in cilia assembly and movement. Furthermore, gene-expression
      differences observed in vitro were concordant with differences observed in airway
      epithelium collected from ECIG users (q < .01). In summary, our data suggest that
      ECIG aerosol can induce gene-expression changes in bronchial airway epithelium in
      vitro, some of which are shared with TCIG smoke. These changes were generally
      less pronounced than the effects of TCIG exposure and were more pronounced in
      ECIG products containing nicotine than those without nicotine. Our data further
      suggest that the gene-expression alterations seen with the in vitro exposure
      system reflects the physiological effects experienced in vivo by ECIG users.

PMID- 27701122
TI  - Cold Plasma Welding System for Surgical Skin Closure: In Vivo Porcine Feasibility
      Assessment.
AB  - BACKGROUND: Cold plasma skin welding is a novel technology that bonds skin edges
      through soldering without the use of synthetic materials or conventional wound
      approximation methods such as sutures, staples, or skin adhesives. The cold
      plasma welding system uses a biological solder applied to the edges of a skin
      incision, followed by the application of cold plasma energy. The objectives of
      this study were to assess the feasibility of a cold plasma welding system in
      approximating and fixating skin incisions compared with conventional methods and
      to evaluate and define optimal plasma welding parameters and histopathological
      tissue response in a porcine model. METHODS AND MATERIALS: The cold plasma
      welding system (BioWeld1 System, IonMed Ltd, Yokneam, Israel) was used on porcine
      skin incisions using variable energy parameters. Wound healing was compared
      macroscopically and histologically to incisions approximated with sutures.
      RESULTS: When compared to sutured skin closure, cold plasma welding in specific
      system parameters demonstrated comparable and favorable wound healing results
      histopathologically as well as macroscopically. No evidence of epidermal damage,
      thermal or otherwise, was encountered in the specified parameters. Notably,
      bleeding, infection, and wound dehiscence were not detected at incision sites.
      Skin incisions welded at extreme energy parameters presented second-degree burns.
      CONCLUSION: Implementation of cold plasma welding has been shown to be feasible
      for skin closure. Initial in vivo results suggest cold plasma welding might
      provide equal, if not better, healing results than traditional methods of
      closure.

PMID- 27701120
TI  - Comprehensive Translational Assessment of Human-Induced Pluripotent Stem Cell
      Derived Cardiomyocytes for Evaluating Drug-Induced Arrhythmias.
AB  - Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for
      assessment of drug-induced arrhythmias and are being considered for use under the
      comprehensive in vitro proarrhythmia assay (CiPA). We studied the effects of 26
      drugs and 3 drug combinations on 2 commercially available iPSC-CM types using
      high-throughput voltage-sensitive dye and microelectrode-array assays being
      studied for the CiPA initiative and compared the results with clinical QT
      prolongation and torsade de pointes (TdP) risk. Concentration-dependent analysis
      comparing iPSC-CMs to clinical trial results demonstrated good correlation
      between drug-induced rate-corrected action potential duration and field potential
      duration (APDc and FPDc) prolongation and clinical trial QTc prolongation. Of 20
      drugs studied that exhibit clinical QTc prolongation, 17 caused APDc prolongation
      (16 in Cor.4U and 13 in iCell cardiomyocytes) and 16 caused FPDc prolongation (16
      in Cor.4U and 10 in iCell cardiomyocytes). Of 14 drugs that cause TdP,
      arrhythmias occurred with 10 drugs. Lack of arrhythmic beating in iPSC-CMs for
      the four remaining drugs could be due to differences in relative levels of
      expression of individual ion channels. iPSC-CMs responded consistently to human
      ether-a-go-go potassium channel blocking drugs (APD prolongation and arrhythmias)
      and calcium channel blocking drugs (APD shortening and prevention of
      arrhythmias), with a more variable response to late sodium current blocking
      drugs. Current results confirm the potential of iPSC-CMs for proarrhythmia
      prediction under CiPA, where iPSC-CM results would serve as a check to ion
      channel and in silico modeling prediction of proarrhythmic risk. A multi-site
      validation study is warranted.

PMID- 27701123
TI  - Burn Wound Healing Activity of Lythrum salicaria L. and Hypericum scabrum L.
AB  - OBJECTIVE: Burns are complicated traumatic injuries caused by several physical or
      chemical factors. Plants with a wide range of secondary metabolites, with
      valuable properties like antioxidant and anti-inflammatory activities, can be a
      promising source of wound healing agents. MATERIALS AND METHODS: Effects of
      hydromethanolic extracts of Lythrum salicaria and Hypericum scabrum, individually
      and in combination, were assessed in second-degree burn wounds in rats in
      comparison to a white oleaginous base (negative control) and silver sulfadiazine
      (positive control). Histological assessments as well as total thiol molecules,
      lipid peroxidation, and total antioxidant power were evaluated in skin tissue
      samples. Total phenol, flavonoids, and tannins along with the antioxidant and
      antimicrobial activities of the extracts were also as- sessed. RESULTS: Total
      phenol, total flavonoid, and total tannin amounts for L. salicaria and H. scabrum
      were 331 +/- 3.7 and 308.1 +/- 5.2 MUg gallic acid/mg extract, 5.8 +/- 0.4 and
      4.3 +/- 0.3 MUg quercetin/mg extract, and 430 +/- 2.33 and 13.4 +/- 0.5 MUg
      tannic acid/mg extract, respectively. H. scabrum significantly inhibited S.
      aureus and L. salicaria moderately suppressed Staphylococcus aureus and Candida
      albicans growth. Wound contraction percentage with L. salicaria and H. scabrum
      was 89.5 +/- 3.7 and 77.6 +/- 4.1, respectively. A well-organized epidermal layer
      and normal appearance in dermis layer were more observable in the L. salicaria
      group. Moreover, L. salicaria ointment individually displayed better influence on
      tissue oxidative stress parameters than H. scabrum and the negative control (P <
      0.05). CONCLUSION: Results of this study clearly confirm the effectiveness of L.
      salicaria topical ointment as a wound healing agent, possibly due to the
      considerable polyphenolic content and antioxidant properties.

PMID- 27701124
TI  - Application of Heparinized Selective Acellular Sheepskin in Wound-healing
      Promotion of Deep Second-degree Burns.
AB  - INTRODUCTION: This study investigated the application of selective sheepskin
      acellular dermal matrix (ADM), combined with the anticoagulant heparin, in the
      wound-healing treatment of deep second-degree burns (DSDB). METHODS: A DSDB model
      was established, and the test animals were randomly divided into 4 groups:
      iodophor gauze (IG), pig ADM (PA), selective sheepskin ADM (SSA), and heparinized
      selective sheepskin ADM (HSSA).The microcirculation of the wound surface,
      pathological structures, healing rates, and fibroblast apoptosis rates were
      observed at different times in each group. RESULTS: At 24, 48, and 72 hours post
      burn, the filling degree of microcirculation in the HSSA group was higher than
      that in all other groups (P < 0.05). On days 14, 21, and 28 post-burn, the wound
      healing rates in the 3 biological-dressing groups were significantly better than
      the rate in the IG group (P < 0.05). On days 14 to 28 post-burn, the number of
      apoptotic fibroblasts in each group had increased significantly, with the number
      in the HSSA group on day 28 being significantly higher than that in the other
      groups (P < 0.05). DISCUSSION: When used in treating burn wounds, HSSA, SSA, and
      PA protect the cellular wound surface and provide an ideal growing environment
      for the fibroblasts and endothelial cells to promote wound healing and scar
      inhibition. CONCLUSION: The selective sheepskin ADM was successfully produced and
      found to exhibit better effects in protecting microcirculation and promoting
      wound healing compared with all other analyzed methods.

PMID- 27701121
TI  - From the Cover: Manganese Stimulates Mitochondrial H2O2 Production in SH-SY5Y
      Human Neuroblastoma Cells Over Physiologic as well as Toxicologic Range.
AB  - Manganese (Mn) is an abundant redox-active metal with well-characterized
      mitochondrial accumulation and neurotoxicity due to excessive exposures. Mn is
      also an essential co-factor for the mitochondrial antioxidant protein, superoxide
      dismutase-2 (SOD2), and the range for adequate intake established by the
      Institute of Medicine Food and Nutrition Board is 20% of the interim guidance
      value for toxicity by the Agency for Toxic Substances and Disease Registry,
      leaving little margin for safety. To study toxic mechanisms over this critical
      dose range, we treated human neuroblastoma SH-SY5Y cells with a series of MnCl2
      concentrations (from 0 to 100 MUM) and measured cellular content to compare to
      human brain Mn content. Concentrations <=10 MUM gave cellular concentrations
      comparable to literature values for normal human brain, whereas concentrations
      >=50 MUM resulted in values comparable to brains from individuals with toxic Mn
      exposures. Cellular oxygen consumption rate increased as a function of Mn up to
      10 MUM and decreased with Mn dose >=50 MUM. Over this range, Mn had no effect on
      superoxide production as measured by aconitase activity or MitoSOX but increased
      H2O2 production as measured by MitoPY1. Consistent with increased production of
      H2O2, SOD2 activity, and steady-state oxidation of total thiol increased with
      increasing Mn. These findings have important implications for Mn toxicity by re
      directing attention from superoxide anion radical to H2O2-dependent mechanisms
      and to investigation over the entire physiologic range to toxicologic range.
      Additionally, the results show that controlled Mn exposure provides a useful cell
      manipulation for toxicological studies of mitochondrial H2O2 signaling.

PMID- 27701125
TI  - The Use of Bovine Collagen-glycosaminoglycan Matrix for Atypical Lower Extremity
      Ulcers.
AB  - The primary purpose of this study was to evaluate the use of bovine collagen
      glycosaminoglycan matrix on atypical lower extremity ulcers. A retrospective
      chart review was performed on patients who underwent application of bovine
      collagen matrix to a lower extremity ulcer with an atypical etiology including
      autoimmune disease, sickle cell anemia, radiation therapy, connective tissue
      disease, vasculitis, or coagulopathy from January 2009 to October 2014. The
      following outcomes were evaluated: rate of ulcer healing and closure, number of
      ulcers that received a split-thickness skin graft, improvement in pain, and
      complications related to the ulcer. Thirty-eight patients with 71 lower extremity
      ulcers were analyzed. The most common ulcer etiolo- gies included rheumatoid
      arthritis, sickle cell anemia, and coagulopa- thy. After application of the
      bovine collagen matrix, 30 (42.3%) ulcers healed at a mean of 220.9 days. Of the
      71 ulcers, 26 (36.6%) re- ceived a split-thickness skin graft after application
      of the matrix and 17 (65.4%) of those went on to complete healing. Ten patients
      had a local infection noted during follow-up, and 5 patients had dehiscence or
      dissociation of the matrix. Atypical lower extremity ulcers, such as those caused
      by autoimmune diseases and sickle cell anemia, proved difficult to heal. This
      case series shows that bovine collagen matrix can be a successful adjunctive
      therapy for the treatment of these challenging ulcers.

PMID- 27701127
TI  - Efficacy and Safety of a Novel Autologous Wound Matrix in the Management of
      Complicated, Chronic Wounds: A Pilot Study.
AB  - INTRODUCTION: The objective of this pilot study was to evaluate the efficacy and
      safety of a novel method using an autologous whole blood clot formed with the
      RedDress Wound Care System (RD1, RedDress Ltd, Israel), a provisional whole blood
      clot matrix used in the treatment of chronic wounds of various etiologies.
      METHODS AND MATERIALS: Patients were treated at the bedside with the whole blood
      clot matrix. Blood was withdrawn from each patient using citrate, mixed with a
      calcium gluconate/kaolin suspension, and injected into an RD1 clotting tray.
      Within 10 minutes, a clot was formed, placed upon the wound, and fixed with
      primary and secondary dressings. Wounds were redressed weekly with a whole blood
      clot matrix. Treatment was terminated when complete healing was achieved, or when
      the clinician determined that the wound could not further improve without
      additional invasive procedures. RESULTS: Seven patients with multiple and serious
      comorbidities and 9 chronic wounds were treated with 35 clot matrices. Complete
      healing was achieved in 7 of 9 wounds (78%). In 1 venous ulcer with a nonhealing
      fistula, 77% healing was achieved. Treatment was terminated in 1 pressure ulcer
      at 82% closure, because an unexpected mechanical trauma resulted in
      deterioration; this was the only adverse event reported, unrelated to the
      product. No systemic adverse events occurred. CONCLUSIONS: This pilot study
      demonstrates the in vitro autologous whole blood clot matrix is effective and
      safe for treating patients with chronic wounds of different etiologies. A larger
      clinical trial is needed to assess the relative success rate of the matrix in
      different types of wounds in a diverse population with comorbidities.

PMID- 27701126
TI  - Management of Open Distal Lower Extremity Wounds With Exposed Tendons Using
      Porcine Urinary Bladder Matrix.
AB  - : Open wounds of the distal third of the leg and foot with an exposed tendon
      present a challenge in wound management and in attaining stable, durable
      coverage. The mobility of the tendon often leads to chronic inflammation that
      impedes wound closure, while the desiccation of the exposed tendon leads to
      progressive tendon necrosis. For the authors' cases, the ability of extracellular
      matrix (ECM) products to modulate wound bed inflammation and facilitate
      constructive remodeling of a wound seemed a reasonable approach in treating these
      wounds, especially in patients who are often poor surgical candidates for more
      advanced reconstructive procedures. METHODS: The authors reviewed 13 patients who
      had open wounds of the distal third of the leg and/or foot that had associated
      tendon involvement in the wound (Achilles, 6; tibialis anterior, 6; and peroneal,
      1). Patients' wounds were treated to total closure. The clinical course and
      patient management is reviewed herein. RESULTS: The authors found newer ECM
      products can provide a more optimal method of management of patients with exposed
      tendons, as compared to prolonged negative pressure wound therapy. CONCLUSION:
      Furthermore, the authors conclude the use of newer ECM products yields a more
      stable, less scarred, reconstructed wound that more closely resembles normal foot
      and ankle appearance compared to other more complex reconstructive operative
      procedures.

PMID- 27701128
TI  - Histogram Planimetry Method for the Measurement of Irregular Wounds.
AB  - INTRODUCTION: Irregularly shaped wounds or flap borders usually require specified
      software or devices to measure their area and follow-up wound healing. In this
      study, an easy way of area measurement called histogram planimetry (HP) for
      wounds with irregular geometric shapes is defined and compared to conventional
      millimetric wound measurement. MATERIALS AND METHODS: Ten irregularly bordered
      geometric shapes were measured by 4 different individuals working as surgical
      assistants using both HP and manual millimetric measurement tools. The amount of
      time for each wound shape calculation as well as the measurements of the wound
      areas were noted. All measurements were compared for each method and between each
      individual using the Wilcoxon signed-rank test. RESULTS: There was no
      statistically significant difference between 2 measurement methods by means of
      measured areas; however, measurement time was significantly lower when the HP
      method was used. There also was no significant difference between the
      individuals' measurements and calculation times. These results indicated that HP
      is useful as a conventional millimetric square wound measurement technique with
      significantly lower measurement times. CONCLUSION: Due to the development of
      photo-editor software technologies, measurements in the surgical field have
      become more accurate and rapid than conventional manual methods without consuming
      the time and energy needed for other studies. A future study including
      comparisons between the presented method and complex computerized measurement
      methods, in terms of duration and accuracy, may provide additional supportive
      data for the authors' method.

PMID- 27701130
TI  - Classic Solitary Kaposi Sarcoma of the Foot in an Immunocompetent Patient: A Case
      Report.
AB  - Kaposi sarcoma (KS) is a tumor derived from endothelial cell lineage caused by
      Kaposi sarcoma-associated virus or human herpesvirus-8. The authors have set
      forth to describe a unique presentation of the classical form of KS in a
      homosexual individual. The authors demonstrate that a full history and physical
      are important in determining how to guide treatment along with ancillary tests,
      which can prove vital to determine management strategy. The authors then provide
      a brief discussion about variants of KS, biopsy techniques, and current treatment
      options available to patients diagnosed with this condition. The patient
      described is a 60-year-old male of Eastern European descent, who is
      immunocompetent in a monogamous homosexual relationship with a new onset and
      rapidly progressing skin lesion on the plantar aspect of his foot. Surgical
      excision of the tumor was performed and surveillance was determined to be the
      treatment of choice.

PMID- 27701131
TI  - Editorial Message: The 'New' Oblivion.

PMID- 27701129
TI  - Biomechanical Skin Property Evaluation for Wounds Treated With Synthetic and
      Biosynthetic Wound Dressings and a Newly Developed Collagen Matrix During Healing
      of Superficial Skin Defects in a Rat Models.
AB  - INTRODUCTION: There is a high prevalence of superficial wounds such as partial
      thickness burns. Treatment of these wounds frequently includes temporary
      application of wound dressings. The aim of this study was to compare a newly
      developed collagen matrix with commonly used temporary skin dressings for
      treatment of partial-thickness skin defects. MATERIALS AND METHODS: Through a
      skin dermatome, 42 standardized superficial skin defects were generated on the
      back of 28 adult male Lewis rats. The wounds were treated with a synthetic wound
      dressing (Suprathel, Polymedics Innovations Inc, Woodstock, GA) (n = 14), a
      biosynthetic skin dressing (Biobrane, Smith & Nephew, Hull, UK) (n = 14), or a
      newly developed bovine collagen matrix, Collagen Cell Carrier (Viscofan
      BioEngineering, Weinheim, Germany) (n = 14). Biomechanical properties of the skin
      were determined and compared every 10 days over a 3-month period of using the
      Cutometer MPA 580 (Courage + Khazaka Electronic GmbH, Cologne, Germany). RESULTS:
      As opposed to healthy skin, statistically significant differences were detected
      between days 10 and 30, and between days 60 and 80, for calculated elasticity
      (Ue), firmness of skin (R0), and overall elasticity (R8). After 3 months, no
      statistically significant differences in skin elasticity were detected between
      the different wound dressings. CONCLUSIONS: The presented results give an
      opportunity to compare the wound dressings used for treatment with respect to
      skin elasticity and reveal the potential of the bovine collagen matrix in the
      treatment of superficial skin defects; therefore the results facilitate further
      evaluation of collagen matrix in surgical applications and regenerative medicine.

PMID- 27701133
TI  - Harmonisation of serum dihydrotestosterone analysis: establishment of an external
      quality assurance program.
AB  - BACKGROUND: Serum dihydrotestosterone (DHT) is an important analyte for the
      clinical assessment of disorders of sex development. It is also reportedly a
      difficult analyte to measure. Currently, there are significant gaps in the
      standardisation of this analyte, including no external quality assurance (EQA)
      program available worldwide to allow for peer review performance of DHT. We
      therefore proposed to establish a pilot EQA program for serum DHT. METHODS: DHT
      was assessed in the 2015 Royal College of Pathologists of Australasia Quality
      Assurance Programs' Endocrine program material. The material's target (i.e.
      "true") values were established using a measurement procedure based on isotope
      dilution gas chromatography (GC) tandem mass spectrometry (MS/MS). DHT calibrator
      values were based on weighed values of pure DHT material (>97.5% purity) from
      Sigma. The allowable limits of performance (ALP) were established as +/-0.1 up to
      0.5 nmol/L and +/-15% for targets >0.5 nmol/L. RESULTS: Target values for the six
      levels of RCPAQAP material for DHT ranged from 0.02 to 0.43 nmol/L (0.01-0.12
      ng/mL). The material demonstrated linearity across the six levels. There were
      seven participating laboratories for this pilot study. Results of the liquid
      chromatography (LC) MS/MS methods were within the ALP; whereas the results from
      the immunoassay methods were consistently higher than the target values and
      outside the ALP. CONCLUSIONS: This report provides the first peer comparison of
      serum DHT measured by mass spectrometry (MS) and immunoassay laboratories.
      Establishment of this program provides one of the pillars to achieve method
      harmonisation. This supports accurate clinical decisions where DHT measurement is
      required.

PMID- 27701132
TI  - Automated bioreactor system for cartilage tissue engineering of human primary
      nasal septal chondrocytes.
AB  - An automated bioreactor system for three-dimensional (3D) cultivation of facial
      cartilage replacement matrices (e.g. whole human auricles) with automatised
      medium exchange, gas flow and temperature control was developed. The measurement
      of O2 saturation and pH value in the medium was performed with a non-invasive
      optical method. The whole system can be observed via remote monitoring worldwide.
      First results demonstrated that the complete system remained sterile throughout a
      period of 42 days. Human chondrocytes migrated into the employed cartilage
      replacement matrix consisting of decellularised porcine nasoseptal cartilage
      (pNSC). Furthermore, an improved migration and new synthesis of aggrecan was
      detected. A first evaluation of the system was conducted by comparison of the
      results from laboratory analysis with computational fluid dynamics (CFD).

PMID- 27701134
TI  - CCLM Award for the Most Cited Paper Recently Published.

PMID- 27701135
TI  - The parental role in adolescent screen related sedentary behavior.
AB  - BACKGROUND: Adolescents spend an increasing amount of their time engaged in
      screen using activities. The present study aimed at identifying parental factors
      associated with screen time among Greek adolescents. METHODS: A sample of 1141
      adolescents, as well as their parents, participated in this survey. Adolescents
      were asked to complete a questionnaire about time spent on screen-viewing
      behaviors. Respectively, parents completed a questionnaire concerning family
      predictors. Multiple regression analysis was used to determine correlates of
      adolescent screen-viewing with family predictors. RESULTS: The mean screen time
      per weekday was 193 min. Adolescents, whose parents had received up to secondary
      school education, spend more time in screen-viewing compared with the other
      groups. Controlling adolescents' gender and age, all the family variables
      (perceived rules, parental modeling, parents' screen related sedentary behavior,
      parental concern for screen viewing, support for physical activity, parental
      education) were statistically significant in predicting adolescent screen time
      with Perceived Rules recording a higher negative beta value (beta=-0.18, p<0.00).
      CONCLUSION: Perceived parental screen time rules play a role in the amount of
      screen time among adolescents. Interventions that focus on parental limit setting
      development and physical activity support may be effective in decreasing screen
      time among youth aged 13-15 years.

PMID- 27701136
TI  - A pilot study of depression, stigma, and attitudes towards seeking professional
      psychological help among Arab adolescents.
AB  - The Arab region has the largest proportion of young people in the world and many
      of the factors that contribute to the onset of depression. Yet, very little is
      known about the current situation of depression and its associated stigma in this
      region. The purpose of this pilot study was to obtain preliminary data examining
      clinically significant depressive symptoms, depression stigma, and attitudes
      towards seeking professional help for depression among a sample of Arab
      adolescents from Jordan. Cross-sectional data were collected from 88 adolescents
      attending public schools in Jordan using self-report questionnaires that were
      available in, or translated into, Arabic. Among the 88 adolescents, 22% reported
      scores suggesting mild depression and 19% reported scores suggesting moderate
      depression, while 24% reported scores suggesting severe depression. The most
      frequently reported depressive symptoms were changes in sleep patterns (76%),
      changes in appetite (63%), agitation (62%), and crying (61%). The majority (73%)
      had moderate depression stigma, and 43% had negative attitudes towards seeking
      professional help. Yet, 67% believed they would find relief in psychotherapy if
      they ever had a serious emotional crisis. Findings suggest that the prevalence of
      depressive symptoms may be high among Jordanian adolescents. Further, many of
      these adolescents may experience depression-related stigma that affects their
      attitudes and willingness to seek professional help. To determine the true scope
      of these issues, including the prevalence of depression among Jordanian
      adolescents, future research should obtain data from a nationally representative
      sample.

PMID- 27701137
TI  - Oxidative stress, histopathological and electron microscopic alterations induced
      by dimethylnitrosamine in renal male mice and the protective effect of alpha
      lipoic acid.
AB  - BACKGROUND: Dimethylnitrosamine (DMN) is a waste product of several industrial
      processes. alpha-Lipoic acid (ALA) is a vitamin-like chemical also called as an
      antioxidant. Therefore, the study was designed to investigate the potential
      benefits of ALA in reducing the nephropathy of DMN in male mice. METHODS: Animals
      were divided into 6 groups (n=8) and received their treatment for 4 weeks as
      follows: groups 1-4 served as control, ALA-treatment (16.12 mg/kg), DMN low dose
      treatment and DMN high dose treatment, respectively. Groups 5 and 6 received ALA
      before DMN low dose and DMN high dose, respectively. Superoxide dismutase,
      catalase, glutathione peroxidase and xanthine oxidase, total antioxidant
      capacity, nitric oxide, lipid peroxidation as well as the levels of uric acid and
      creatinine were determined. The histological and ultrastructure changes of renal
      tissue were also evaluated. RESULTS: Treatment of the DMN mice with ALA showed a
      reduction in the levels of kidney nitric oxide, lipid peroxidation, as well as
      creatinine and uric acid levels as compared with the DMN group. The results show
      that ALA plays an important role in quenching the free radicals resulting from
      the metabolism of DMN, thereby inhibiting lipid peroxidation and protecting
      membrane lipids from oxidative damage and, in turn, preventing oxidative stress
      and apoptosis. Histopathological and ultrastructure analysis of renal tissue
      confirmed the oxidative stress results occurred in DMN renal mice. Concomitant
      administration of ALA with DMN significantly decreased all the histopathological
      changes induced by DMN. CONCLUSIONS: The present study elucidated the therapeutic
      effects of ALA administered in combination with DMN to minimize its renal
      toxicity.

PMID- 27701138
TI  - The ameliorating effect of Centella asiatica ethanolic extract on albino rats
      treated with isoniazid.
AB  - BACKGROUND: Isoniazid, also called isonicotinyl hydrazine (INH), is a commonly
      used drug for treating tuberculosis. The main drawback is its toxic side effects.
      Centella asiatica has long been used in the Ayurvedic system of medicine owing to
      its wide medicinal properties. This study was designed to examine the
      effectiveness of C. asiatica ethanolic leaf extract (CA) on INH-treated albino
      rats. METHODS: The adverse effects induced by INH (50 mg/kg bw) administration on
      haematological parameters, oxidative status (thiobarbituric acid-reactive
      substances, superoxide dismutase, catalase, and reduced glutathione), liver and
      kidney function markers, and their amelioration by various concentrations of CA
      (20, 40, 60, and 100 mg/kg bw) or silymarin (SIL) (50 mg/kg bw, administered
      before 1 h of INH treatment for 30 days to rats) were studied. Moreover,
      histological studies were carried out in liver and kidney tissues of rats treated
      with the most effective concentration to further support the possible
      effectiveness of CA on INH-intoxicated rats. RESULTS: All the affected parameters
      returned to near-normal levels, and the effective concentration of extract was
      found to be 100 mg/kg bw. The histology of both the liver and the kidneys
      subsequently supported the effectiveness of CA (100 mg/kg bw). CONCLUSIONS:
      Altogether, the results suggest that CA at 100 mg/kg bw can substantially reduce
      the toxic effects of INH.

PMID- 27701139
TI  - Epigenomic reprogramming in inorganic arsenic-mediated gene expression patterns
      during carcinogenesis.
AB  - Arsenic is a ubiquitous metalloid that is not mutagenic but is carcinogenic. The
      mechanism(s) by which arsenic causes cancer remain unknown. To date, several
      mechanisms have been proposed, including the arsenic-induced generation of
      reactive oxygen species (ROS). However, it is also becoming evident that
      inorganic arsenic (iAs) may exert its carcinogenic effects by changing the
      epigenome, and thereby modifying chromatin structure and dynamics. These
      epigenetic changes alter the accessibility of gene regulatory factors to DNA,
      resulting in specific changes in gene expression both at the levels of
      transcription initiation and gene splicing. In this review, we discuss recent
      literature reports describing epigenetic changes induced by iAs exposure and the
      possible epigenetic mechanisms underlying these changes.

PMID- 27701140
TI  - Leaves of Cordia boissieri A. DC. as a potential source of bioactive secondary
      metabolites for protection against metabolic syndrome-induced in rats.
AB  - Cordia boissieri A. DC. (Boraginaceae) is traditionally used as an herbal remedy
      for diabetes by Hispanic women in Southwestern USA. A recent investigation showed
      the significant protective effect of ethyl acetate extract against metabolic
      syndrome (MS). However, the corresponding active principles responsible for this
      effect and relations between their structure and biological actions remain
      unclear. Thus, ethyl acetate extract was subjected to column chromatography,
      which yielded seven compounds identified on the basis of spectroscopic data as
      rutin, hesperidin, kaempferol-3-O-beta-d-glucopyranoside, rosmarinic acid, beta
      sitosterol-3-O-beta-d-glucopyranoside, quercetin, and kaempferol. The isolated
      compounds (5 mg/kg/day) were tested in a fructose enriched-diet rat model using
      metformin as a standard drug. Blood samples were withdrawn for estimation of MS
      associated biomarkers and liver samples were subjected to histopathological and
      immunohistochemical examination. The isolated compounds impaired most of the
      changes associated with MS as evidenced by improved insulin sensitivity, glucose
      tolerance, kidney function, lipid profiles and reduced oxidative stress and
      inflammation by different degrees. It is worth noting that quercetin and
      kaempferol showed the most potent effect. Structure-activity relationship study
      revealed that the presence of 2,3-double bond in ring C and ortho-hydroxylation
      in ring B increases the flavonoids activity while glycosylation or methylation
      decreased this activity.

PMID- 27701141
TI  - Cytochalasin P1, a new cytochalasin from the marine-derived fungus Xylaria sp.
      SOF11.
AB  - A new cytochalasin, named cytochalasin P1 (1), together with four known analogs
      (2-5) was isolated from marine-derived fungus Xylaria sp. SOF11 from the South
      China Sea. The structure of the new compound was elucidated on the basis of MS
      and NMR (1H, 13C, HSQC, HMBC, and NOESY) data analyses. Compounds 1-5 were tested
      for their cytotoxicities against four tumor cell lines (SF-268, MCF-7, NCI-H460,
      and HepG-2). Compounds 1-5 showed significant cytotoxicity against two tumor cell
      lines MCF-7 and SF-268, with the IC50 values varying between 0.33 and 4.17 MUM.

PMID- 27701142
TI  - Caspase-1 from the silkworm, Bombyx mori, is involved in Bombyx mori
      nucleopolyhedrovirus infection.
AB  - Caspase-1 is one of the effector caspases in mammals that plays a central role in
      apoptosis. However, the lepidopteran caspase-1, especially the Bombyx mori
      caspase-1 (Bm-caspase-1), has not been investigated in detail. In this study, Bm
      caspase-1 was identified from an expressed sequence tag database in B. mori by
      BLAST search. The open reading frame of Bm-caspase-1 contained 879 nucleotides
      and encoded 293 amino acids with a predicted molecular mass of 33 kDa. Bm-caspase
      1 contained two consensus amino acid motifs of caspase cleavage sites, DEGDA and
      TETDG. Caspase activity assays revealed significant proteolytic activity of the
      Ac-DEVD-pNA substrate. Bm-caspase-1 can be detected in all tissues and
      developmental stages by a semi quantitative polymerase chain reaction assay. More
      importantly, the expression level of Bm-caspase-1 is increased upon baculovirus
      infection and up-regulated in BmNPV-resistant silkworms. Taken together, these
      results indicate that Bm-caspase-1 plays an important role during baculovirus
      infection.

PMID- 27701143
TI  - Ultrafast domain wall dynamics in magnetic nanotubes and nanowires.
AB  - The dynamic properties of magnetic domain walls in nanotubes and in cylindrical
      nanowires can be significantly different from the well known domain wall dynamics
      in thin films and in flat thin strips. The main differences are the occurrence of
      chiral symmetry breaking and, perhaps more importantly, the possibility to obtain
      magnetic domain walls that are stable against the usual Walker breakdown. This
      stability enables the magnetic field-driven propagation of the domain walls in
      nanotubes and nanocylinders at constant velocities which are significantly higher
      than the usual propagation speeds of the domain walls. Simulations predict that
      the ultrafast motion of magnetic domain walls at velocities in a range above 1000
      m s-1 can lead to the spontaneous excitation of spin waves in a process that is
      the magnetic analog of the Cherenkov effect. In the case of solid cylindrical
      wires, the domain wall can contain a micromagnetic point singularity. We discuss
      the current knowledge on the ultrafast dynamics of such Bloch points, which
      remains still largely unexplored.

PMID- 27701144
TI  - Thermal transport phenomena in nanoparticle suspensions.
AB  - Nanoparticle suspensions in liquids have received great attention, as they may
      offer an approach to enhance thermophysical properties of base fluids. A good
      variety of applications in engineering and biomedicine has been investigated with
      the aim of exploiting the above potential. However, the multiscale nature of
      nanosuspensions raises several issues in defining a comprehensive modelling
      framework, incorporating relevant molecular details and much larger scale
      phenomena, such as particle aggregation and their dynamics. The objectives of the
      present topical review is to report and discuss the main heat and mass transport
      phenomena ruling macroscopic behaviour of nanosuspensions, arising from molecular
      details. Relevant experimental results are included and properly put in the
      context of recent observations and theoretical studies, which solved long
      standing debates about thermophysical properties enhancement. Major transport
      phenomena are discussed and in-depth analysis is carried out for highlighting the
      role of geometrical (nanoparticle shape, size, aggregation, concentration),
      chemical (pH, surfactants, functionalization) and physical parameters
      (temperature, density). We finally overview several computational techniques
      available at different scales with the aim of drawing the attention on the need
      for truly multiscale predictive models. This may help the development of next
      generation nanoparticle suspensions and their rational use in thermal
      applications.

PMID- 27701145
TI  - Decreased somatic hypermutation induces an impaired peripheral B cell tolerance
      checkpoint.
AB  - Patients with mutations in AICDA, which encodes activation-induced cytidine
      deaminase (AID), display an impaired peripheral B cell tolerance. AID mediates
      class-switch recombination (CSR) and somatic hypermutation (SHM) in B cells, but
      the mechanism by which AID prevents the accumulation of autoreactive B cells in
      blood is unclear. Here, we analyzed B cell tolerance in AID-deficient patients,
      patients with autosomal dominant AID mutations (AD-AID), asymptomatic AICDA
      heterozygotes (AID+/-), and patients with uracil N-glycosylase (UNG) deficiency,
      which impairs CSR but not SHM. The low frequency of autoreactive mature naive B
      cells in UNG-deficient patients resembled that of healthy subjects, revealing
      that impaired CSR does not interfere with the peripheral B cell tolerance
      checkpoint. In contrast, we observed decreased frequencies of SHM in memory B
      cells from AD-AID patients and AID+/- subjects, who were unable to prevent the
      accumulation of autoreactive mature naive B cells. In addition, the individuals
      with AICDA mutations, but not UNG-deficient patients, displayed Tregs with
      defective suppressive capacity that correlated with increases in circulating T
      follicular helper cells and enhanced cytokine production. We conclude that SHM,
      but not CSR, regulates peripheral B cell tolerance through the production of
      mutated antibodies that clear antigens and prevent sustained interleukin
      secretions that interfere with Treg function.

PMID- 27701146
TI  - Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing
      AMPK-mediated thermogenesis.
AB  - Enhancing energy expenditure (EE) is an attractive strategy to combat obesity and
      diabetes. Global deletion of Ip6k1 protects mice from diet-induced obesity (DIO)
      and insulin resistance, but the tissue-specific mechanism by which IP6K1
      regulates body weight is unknown. Here, we have demonstrated that IP6K1 regulates
      fat accumulation by modulating AMPK-mediated adipocyte energy metabolism. Cold
      exposure led to downregulation of Ip6k1 in murine inguinal and retroperitoneal
      white adipose tissue (IWAT and RWAT) depots. Adipocyte-specific deletion of Ip6k1
      (AdKO) enhanced thermogenic EE, which protected mice from high-fat diet-induced
      weight gain at ambient temperature (23 degrees C), but not at thermoneutral
      temperature (30 degrees C). AdKO-induced increases in thermogenesis also
      protected mice from cold-induced decreases in body temperature. UCP1, PGC1alpha,
      and other markers of browning and thermogenesis were elevated in IWAT and RWAT of
      AdKO mice. Cold-induced activation of sympathetic signaling was unaltered,
      whereas AMPK was enhanced, in AdKO IWAT. Moreover, beige adipocytes from AdKO
      IWAT displayed enhanced browning, which was diminished by AMPK depletion.
      Furthermore, we determined that IP6 and IP6K1 differentially regulate upstream
      kinase-mediated AMPK stimulatory phosphorylation in vitro. Finally, treating
      mildly obese mice with the IP6K inhibitor TNP enhanced thermogenesis and
      inhibited progression of DIO. Thus, IP6K1 regulates energy metabolism via a
      mechanism that could potentially be targeted in obesity.

PMID- 27701150
TI  - Nanoparticle Technologies in the Spinal Cord.
AB  - Nanoparticles are increasingly being studied within experimental models of spinal
      cord injury (SCI). They are used to image cells and tissue, move cells to
      specific regions of the spinal cord, and deliver therapeutic agents locally. The
      focus of this article is to provide a brief overview of the different types of
      nanoparticles being studied for spinal cord applications and present data showing
      the capability of nanoparticles to deliver the chondroitinase ABC (chABC) enzyme
      locally following acute SCI in rats. Nanoparticles releasing chABC helped promote
      axonal regeneration following injury, and the nanoparticles also protected the
      enzyme from rapid degradation. In summary, nanoparticles are viable materials for
      diagnostic or therapeutic applications within experimental models of SCI and have
      potential for future clinical use.

PMID- 27701148
TI  - Inhibition of CDK4/6 protects against radiation-induced intestinal injury in
      mice.
AB  - Radiotherapy causes dose-limiting toxicity and long-term complications in rapidly
      renewing tissues, including the gastrointestinal tract. Currently, there is no
      FDA-approved agent for the prevention or treatment of radiation-induced
      intestinal injury. In this study, we have shown that PD 0332991 (PD), an FDA
      approved selective inhibitor of cyclin-dependent kinase 4/6 (CDK4/6), prevents
      radiation-induced lethal intestinal injury in mice. Treating mice with PD or a
      structurally distinct CDK4/6 inhibitor prior to radiation blocked proliferation
      and crypt apoptosis and improved crypt regeneration. PD treatment also enhanced
      LGR5+ stem cell survival and regeneration after radiation. PD was an on-target
      inhibitor of RB phosphorylation and blocked G1/S transition in the intestinal
      crypts. PD treatment strongly but reversibly inhibited radiation-induced p53
      activation, which blocked p53-upregulated modulator of apoptosis-dependent (PUMA
      dependent) apoptosis without affecting p21-dependent suppression of DNA damage
      accumulation, with a repair bias toward nonhomologous end joining. Further,
      deletion of PUMA synergized with PD treatment for even greater intestinal
      radioprotection. Our results demonstrate that the cell cycle critically regulates
      the DNA damage response and survival of intestinal stem cells and support the
      concept that pharmacological quiescence is a potentially highly effective and
      selective strategy for intestinal radioprotection.

PMID- 27701147
TI  - Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support
      pancreatic cancer aggressiveness.
AB  - The intratumoral microenvironment, or stroma, is of major importance in the
      pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions
      in the stroma may promote increased cancer aggressiveness. We hypothesized that
      this heterogeneous and evolving compartment drastically influences tumor cell
      abilities, which in turn influences PDA aggressiveness through crosstalk that is
      mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA
      proteomic stromal signature and identified a contribution of the annexin A6/LDL
      receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor
      cell crosstalk. Formation of the ANXA6/LRP1/TSP1 complex was restricted to cancer
      associated fibroblasts (CAFs) and required physiopathologic culture conditions
      that improved tumor cell survival and migration. Increased PDA aggressiveness was
      dependent on tumor cell-mediated uptake of CAF-derived ANXA6+ EVs carrying the
      ANXA6/LRP1/TSP1 complex. Depletion of ANXA6 in CAFs impaired complex formation
      and subsequently impaired PDA and metastasis occurrence, while injection of CAF
      derived ANXA6+ EVs enhanced tumorigenesis. We found that the presence of ANXA6+
      EVs in serum was restricted to PDA patients and represents a potential biomarker
      for PDA grade. These findings suggest that CAF-tumor cell crosstalk supported by
      ANXA6+ EVs is predictive of PDA aggressiveness, highlighting a therapeutic target
      and potential biomarker for PDA.

PMID- 27701151
TI  - The Body Acoustic: Ultrasonic Neuromodulation for Translational Medicine.
AB  - For the greater part of the last century, ultrasound (US) has seen widespread use
      in applications ranging from materials science to medicine. The history of US in
      medicine has also seen promising success in clinical diagnostics and regenerative
      medicine. Recent studies have shown that US is able to manipulate the nervous
      system, leading toward potential treatment for various neuropathological
      conditions, a phenomenon known as ultrasonic neuromodulation (NM). Ultrasonic NM
      is a promising alternative to pharmaceuticals and surgery, due to high
      spatiotemporal resolution combined with the potentially noninvasive means of
      application. Current advances have made progress in establishing effective dosage
      limits, waveform parameters, and stimulus regimes in order to achieve desired
      effects in a variety of tissue and cell types. However, to date there has been
      limited systematic analysis of the complex variables involved in creating a
      therapeutic US stimulation regime specifically tailored to the nervous system.
      Without a fundamental understanding of the effects of US on neural tissue,
      including the surrounding bone, musculature, and vasculature, the safety and
      efficacy of US as an NM tool is yet to be determined. Advances in imaging
      technology and focusing hardware highlight new avenues for potential clinical
      applications for therapeutic ultrasonic stimulation. US may be an alternative to
      electrical and magnetic means of NM for targets in the central nervous system as
      well as in the peripheral and autonomic nervous systems. This review provides a
      historical perspective on the past, present, and future of US as a translational
      therapeutic.

PMID- 27701149
TI  - MST1-dependent vesicle trafficking regulates neutrophil transmigration through
      the vascular basement membrane.
AB  - Neutrophils need to penetrate the perivascular basement membrane for successful
      extravasation into inflamed tissue, but this process is incompletely understood.
      Recent findings have associated mammalian sterile 20-like kinase 1 (MST1) loss of
      function with a human primary immunodeficiency disorder, suggesting that MST1 may
      be involved in immune cell migration. Here, we have shown that MST1 is a critical
      regulator of neutrophil extravasation during inflammation. Mst1-deficient (Mst1-/
      ) neutrophils were unable to migrate into inflamed murine cremaster muscle
      venules, instead persisting between the endothelium and the basement membrane.
      Mst1-/- neutrophils also failed to extravasate from gastric submucosal vessels in
      a murine model of Helicobacter pylori infection. Mechanistically, we observed
      defective translocation of VLA-3, VLA-6, and neutrophil elastase from
      intracellular vesicles to the surface of Mst1-/- neutrophils, indicating that
      MST1 is required for this crucial step in neutrophil transmigration. Furthermore,
      we found that MST1 associates with the Rab27 effector protein synaptotagmin-like
      protein 1 (JFC1, encoded by Sytl1 in mice), but not Munc13-4, thereby regulating
      the trafficking of Rab27-positive vesicles to the cellular membrane. Together,
      these findings highlight a role for MST1 in vesicle trafficking and extravasation
      in neutrophils, providing an additional mechanistic explanation for the severe
      immune defect observed in patients with MST1 deficiency.

PMID- 27701154
TI  - Cytological Characteristics of Endometrial Phasing Using the Specimens Prepared
      with the Liquid-Based Procedure: Comparison with the Conventional Procedure.
AB  - OBJECTIVE: To evaluate whether or not the liquid-based procedure (LBP) for
      endometrial cytology is as worthwhile for endometrial phasing as conventional
      slides. MATERIALS AND METHODS: The subjects were 81 women who underwent
      endometrial cytology and were defined as negative. The specimens obtained by
      either Endocyte(r) or Masubuchi aspiration tube(r) were processed first with the
      conventional procedure and then with LBP using TACASTM. RESULTS: (1) The number
      of subjects diagnosed by the conventional method as having proliferative, mid-,
      middle-secretory and late-secretory and atrophic phases was 40, 11, 10, 0 and 20,
      respectively. The rate of agreement with those using LBP was 87.7%. (2)
      Incidences of large clusters, ductal clusters, palisade arrangement, uneven
      staining and dirty mucous background detected were significantly higher with the
      conventional method, whereas with LBP clean background, inconspicuous bonding of
      cells, scattered solitary glandular cells, clear well-stained cytoplasm and cell
      compactness were higher. (3) Especially in the proliferative phase, clusters
      tended to be smaller and lose their architectural structures, and scattered
      solitary columnar cells were present. (4) Cells in the mid-phase tended to have
      loose contact and to mimic other phases. CONCLUSIONS: Cytodiagnosis of
      endometrial phasing prepared with LBP is feasible to perform when some
      modifications are implemented.

PMID- 27701153
TI  - Electrospun Fibers for Drug Delivery after Spinal Cord Injury and the Effects of
      Drug Incorporation on Fiber Properties.
AB  - There is currently no cure for individuals with spinal cord injury (SCI). While
      many promising approaches are being tested in clinical trials, the complexity of
      SCI limits several of these approaches from aiding complete functional recovery.
      Several different categories of biomaterials are investigated for their ability
      to guide axonal regeneration, to deliver proteins or small molecules locally, or
      to improve the viability of transplanted stem cells. The purpose of this study is
      to provide a brief overview of SCI, present the different categories of
      biomaterial scaffolds that direct and guide axonal regeneration, and then focus
      specifically on electrospun fiber guidance scaffolds. Much like other polymer
      guidance approaches, electrospun fibers can retain and deliver therapeutic drugs.
      The experimental section presents new data showing the incorporation of two
      therapeutic drugs into electrospun poly-L-lactic acid fibers. Two different
      concentrations of either riluzole or neurotrophin-3 were loaded into the
      electrospun fibers to examine the effect of drug concentration on the physical
      characteristics of the fibers (fiber alignment and fiber diameter). Overall, the
      drugs were successfully incorporated into the fibers and the release was related
      to the loading concentration. The fiber diameter decreased with the inclusion of
      the drug, and the decreased diameter was correlated with a decrease in fiber
      alignment. Subsequently, the study includes considerations for successful
      incorporation of a therapeutic drug without changing the physical properties of
      the fibers.

PMID- 27701155
TI  - Long-Term Follow-Up Is Essential to Assess Outcome of Gastric Banding in Morbidly
      Obese Adolescents: A Retrospective Analysis.
AB  - BACKGROUND: Adolescent obesity is rapidly becoming more prevalent and is
      associated with chronic health conditions and psychosocial morbidity. Lifestyle
      intervention is often ineffective in morbidly obese adolescents, and bariatric
      surgery is gradually becoming an accepted treatment. However, little is known
      about long-term results. METHODS: Hospital charts of patients who had undergone
      gastric banding more than 5 years ago at an age of 18 years or younger, were
      retrospectively analyzed. Weight loss, complications, reoperations, and
      comorbidity reduction were assessed as well as health status, food behavior, and
      personality. RESULTS: BMI loss in 10 adolescents was 10.7 kg/m2 (-0.9 to 12.9
      kg/m2) after a median follow-up of 64 months (52-84 months); the major part of
      weight loss occurred after the first year. In 4 patients the gastric band was
      removed after 3.5-5.5 years. Two out of 3 patients effectively lost weight after
      conversion to a bypass type procedure. One patient is maintaining a stable
      healthy weight after band removal. CONCLUSIONS: Laparoscopic adjustable gastric
      banding in morbidly obese adolescents had a failure rate of 40%, but was a
      successful therapy in the other 60% without major adverse events. Follow-up
      longer than 36 months was crucial for optimal evaluation of weight loss and
      reoperation rate.

PMID- 27701152
TI  - Tissue Engineering Approaches to Modulate the Inflammatory Milieu following
      Spinal Cord Injury.
AB  - Tissue engineering strategies have shown promise in promoting healing and
      regeneration after spinal cord injury (SCI); however, these strategies are
      limited by inflammation and the immune response. Infiltration of cells of the
      innate and adaptive immune responses and the inflammation that follows cause
      secondary damage adjacent to the injury, increased scarring, and a potently
      inhibitory environment for the regeneration of damaged neurons. While the
      inflammation that ensues is typically associated with limited regeneration, the
      immune response is a crucial element in the closing of the blood-brain barrier,
      minimizing the spread of injury, and initiating healing. This review summarizes
      the strategies that have been developed to modulate the immune response towards
      an anti-inflammatory environment that is permissive to the regeneration of
      neurons, glia, and parenchyma. We focus on the use of biomaterials, biologically
      active molecules, gene therapy, nanoparticles, and stem cells to modulate the
      immune response, and illustrate concepts for future therapies. Current clinical
      treatments for SCI are limited to systemic hypothermia or methylprednisolone,
      which both act by systemically mitigating the effects of immune response but have
      marginal efficacy. Herein, we discuss emerging research strategies to further
      enhance these clinical treatments by directly targeting specific aspects of the
      immune response.

PMID- 27701156
TI  - Improving Peripheral and Central Vascular Adjustments during Exercise through a
      Training Program in Adolescents with Obesity.
AB  - OBJECTIVE: The effects of a training program (TP) on muscle microvascularization
      during exercise remained to be explored in adolescents with obesity. We
      hypothesized that a TP would lead to better microvascular adaptations to exercise
      in skeletal muscle. METHODS: 15 inactive adolescents followed a 12-week TP where
      both peripheral (muscular microvascularization) and central (cardiac) adaptations
      to exercise (40 min exercise set at 70% VO2peak) were assessed before and after
      intervention. Microvascular adaptations were evaluated in the Musculus vastus
      lateralis with near-infrared spectroscopy, by measurement of muscular blood
      volume (IR-BV) and tissue oxygen saturation (IR-SO2). Central adaptations were
      evaluated using thoracic impedance. RESULTS: The TP favored lower BMI (p <
      0.001), lower total and abdominal fat (p < 0.001), and a trend for the decrease
      in insulin resistance index (p = 0.07). VO2peak relative to weight (p = 0.008)
      and maximum power output increased (p = 0.0003). A smaller initial drop in IR-BV
      and IR-SO2 (p < 0.001), a prompter return of these parameters to their base
      values, and a higher IR-BV and IR-SO2 all times taken together (p < 0.001) were
      observed after completing the TP. Concerning central adaptation, cardiac output
      decreased (p < 0.001). CONCLUSION: We demonstrate for the first time by
      noninvasive techniques that a training program induces peripheral and central
      vascular adaptations to exercise in adolescents with obesity.

PMID- 27701158
TI  - Acquired FVIII and FIX Inhibitors after Pregnancy: A Case Report.
AB  - Acquired hemophilia is a relatively rare clinical presentation, and most cases
      present with acquired FVIII inhibitor. The co-occurrence of inhibitors to
      multiple coagulation factors is uncommon. These autoantibodies may induce
      spontaneous life-threatening bleeding in patients who have had no previous
      bleeding disorder. Herein, we present a patient with postpartum acquired FVIII
      and FIX inhibitors who developed intramuscular hematoma and hemothorax during
      follow-up. She was then treated with activated prothrombin complex concentrate
      and methylprednisolone.

PMID- 27701157
TI  - Truncating Wilms Tumor Suppressor Gene 1 Mutation in an XX Female with Adult
      Onset Focal Segmental Glomerulosclerosis and Streak Ovaries: A Case Report.
AB  - About 30% of children with nephrotic syndrome (NS) have inherited forms. Among
      them, mutations in Wilms tumor suppressor gene 1 (WT1) are a well characterized
      cause associated with steroid-resistant NS, Wilms tumor, and urogenital
      malformation in males. However, the role of WT1 mutations in adult-onset focal
      segmental glomerulosclerosis (FSGS) is unclear. We report the case of a 38-year
      old female with FSGS. She had been diagnosed with streak ovaries during
      diagnostic workup for infertility. Mutational analysis identified the
      heterozygous mutation c.1372C>T (p.Arg458*) in WT1 and the heterozygous non
      neutral polymorphism c.868G>A (p.Arg229Gln) in NPHS2. Chromosomal analysis
      revealed a normal 46,XX female karyotype. Our case highlights that WT1 mutations
      should be considered in XX females with adult-onset FSGS, especially if
      urogenital abnormalities are present.

PMID- 27701159
TI  - The Clinical Outcomes after Total Pancreatectomy.
AB  - BACKGROUND: Total pancreatectomy (TP) is not more beneficial than less aggressive
      resection techniques for the treatment of pancreatic neoplasms and is associated
      with high morbidity and mortality. However, with advances in surgical techniques
      and glycemic monitoring, and the development of synthetic insulin and pancreatic
      enzymes for postoperative treatment, TP has been increasingly indicated. This is
      a review of the recent literature reporting the clinical outcomes after TP.
      METHODS: We reviewed the publications reporting the use of TP starting 2007. The
      clinicophysiological and survival data were analyzed. RESULTS: Few studies
      evaluated the differences in clinical outcomes between TP and
      pancreaticoduodenectomy (PD) with inconsistent results. It was reported that
      while the perioperative morbidity did not decrease, the mortality decreased
      compared to previous literature. All patients who underwent TP required insulin
      and high dose of pancreatic enzyme supplements. The 5-year survival rates after
      TP and PD for pancreatic cancer were similar. CONCLUSION: The perioperative
      mortality decreased in patients who underwent TP with advances in the operative
      procedures and perioperative care. The long-term survival rates were similar for
      TP and PD. Therefore, treating pancreatic neoplasms using TP is feasible.
      Patients undergoing TP should receive adequate treatment with synthetic insulin
      and pancreatic enzyme supplements.

PMID- 27701160
TI  - Cognitive Impairment Is Associated with a Low Omega-3 Index in the Elderly:
      Results from the KORA-Age Study.
AB  - BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFA) may affect the risk of
      cognitive decline in older adults. METHODS: Cross-sectional analysis was
      conducted among 720 (50.4% women) participants aged 68-92 years (mean age: 77.6,
      SD +/-6.2) of the population-based KORA-Age study. Eicosapentaenoic acid and
      docosahexaenoic acid (omega-3 index) were measured in erythrocytes as a
      percentage of total fatty acids. The categories low (<5.7), intermediate (5.7
      6.8), and high (>6.8) levels of the omega-3 index were built using tertiles. The
      association between cognitive status and omega-3 levels was assessed by logistic
      regression analyses with adjustments for important concurrent risk factors of
      cognitive decline. RESULTS: In the sex- and age-adjusted model (model 1),
      subjects with a low omega-3 index were at a significantly higher risk for
      cognitive impairment (OR: 1.77, 95% CI: 1.15-2.73, p = 0.009). This association
      remained stable after further adjusting for educational level (model 2; OR: 1.75,
      95% CI: 1.13-2.71, p = 0.01) and metabolic risk factors (model 3; OR: 1.77, 95%
      CI: 1.14-2.75, p = 0.01). After further controlling for affective disorders
      (model 4), the association did not attenuate (OR: 1.77, 95% CI: 1.14-2.76, p =
      0.01). CONCLUSION: A robust association was found between low omega-3 levels and
      cognitive impairment in an elderly population. Further research is needed to
      understand the link between omega-3 PUFA and cognitive functioning.

PMID- 27701161
TI  - Bioelectric Medicine and Devices for the Treatment of Spinal Cord Injury.
AB  - Recovery of motor control is paramount for patients living with paralysis
      following spinal cord injury (SCI). While a cure or regenerative intervention
      remains on the horizon for the treatment of SCI, a number of neuroprosthetic
      devices have been employed to treat and mitigate the symptoms of paralysis
      associated with injuries to the spinal column and associated comorbidities. The
      recent success of epidural stimulation to restore voluntary motor function in the
      lower limbs of a small cohort of patients has breathed new life into the promise
      of electric-based medicine. Recently, a number of new organic and inorganic
      electronic devices have been developed for brain-computer interfaces to bypass
      the injury, for neurorehabilitation, bladder and bowel control, and the
      restoration of motor or sensory control. Herein, we discuss the recent advances
      in neuroprosthetic devices for treating SCI and highlight future design needs for
      closed-loop device systems.

PMID- 27701162
TI  - Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal
      Pressure.
AB  - Spinal cord injury (SCI) is a devastating condition that leaves patients with
      limited motor and sensory function at and below the injury site, with little to
      no hope of a meaningful recovery. Because of their ability to mimic multiple
      features of central nervous system (CNS) tissues, injectable hydrogels are being
      developed that can participate as therapeutic agents in reducing secondary injury
      and in the regeneration of spinal cord tissue. Injectable biomaterials can
      provide a supportive substrate for tissue regeneration, deliver therapeutic
      factors, and regulate local tissue physiology. Recent reports of increasing
      intraspinal pressure after SCI suggest that this physiological change can
      contribute to injury expansion, also known as secondary injury. Hydrogels contain
      high water content similar to native tissue, and many hydrogels absorb water and
      swell after formation. In the case of injectable hydrogels for the spinal cord,
      this process often occurs in or around the spinal cord tissue, and thus may
      affect intraspinal pressure. In the future, predictable swelling properties of
      hydrogels may be leveraged to control intraspinal pressure after injury. Here, we
      review the physiology of SCI, with special attention to the current clinical and
      experimental literature, underscoring the importance of controlling intraspinal
      pressure after SCI. We then discuss how hydrogel fabrication, injection, and
      swelling can impact intraspinal pressure in the context of developing injectable
      biomaterials for SCI treatment.

PMID- 27701164
TI  - Out-Patient Management of Mild or Uncomplicated Diverticulitis: A Systematic
      Review.
AB  - BACKGROUND: Management of diverticular disease has undergone a paradigm shift,
      with movement towards a less invasive management strategy. In keeping with this,
      outpatient management of uncomplicated diverticulitis (UD) has been advocated in
      several studies, but concerns still remain regarding the safety of this practice.
      AIM: To assess outcomes of out-patient management of acute UD. METHODS: A
      comprehensive search for published studies using the search terms 'uncomplicated
      diverticulitis', 'mild diverticulitis' and 'out-patient' was performed. The
      primary outcomes were failure of medical treatment. Secondary outcomes were
      recurrence rate at follow up and medical cost savings. RESULTS: The search
      yielded 192 publications. Of these, 10 studies met the inclusion criteria
      including 1 randomized controlled trial, 6 clinical controlled trials and 3 case
      series. There was no difference in failure rates of medical treatment (6.5 vs.
      4.6%, p = 0.32) or in recurrence rates (13.0 vs. 12.1%, p = 0.81) between those
      receiving ambulatory care and in-patient care for UD. Ambulatory treatment is
      associated with an estimated daily cost savings of between 600 and 1,900 euros
      per patient treated. Meta-analysis of data was not possible due to heterogeneity
      in study designs and inclusion criteria. CONCLUSION: Ambulatory management of
      acute UD is reasonable in selected patients.

PMID- 27701163
TI  - White Matter Changes May Precede Gray Matter Loss in Elderly with Subjective
      Memory Impairment.
AB  - BACKGROUND/AIMS: A limited number of studies addressed MRI-based
      neurodegenerative changes in subjective memory impairment (SMI). We investigated
      changes in white matter (WM) microstructures as well as gray matter (GM)
      macrostructures in subjects with SMI of high and low risk for progression.
      METHODS: A modeling scale (score range, 0-6) developed for prediction of SMI
      progression was used to divide SMI subjects (n = 46) into two groups: a high risk
      of progression (score >=3; n = 19) and a low risk of progression (score <=2; n =
      27). Cross-sectional comparisons were performed using a region-of-interest-based
      diffusion tensor imaging (DTI) analysis, cortical thickness analysis, and
      hippocampal volumetry. RESULTS: The high-risk group had more microstructural
      disruption shown by lower fractional anisotropy in the hippocampus,
      parahippocampal gyrus, supramarginal gyrus, and parts of frontotemporal lobes. On
      the other hand, GM macrostructural changes did not differ between the groups and
      were not associated with modeling scale scores. CONCLUSION: SMI subjects with a
      high risk of progression had more WM microstructural disruption than those with a
      low risk, and the changes were not explained by GM atrophy. Our findings suggest
      that the degree of microstructural alterations in SMI may be distinctive
      according to the risk factors and may precede GM atrophy.

PMID- 27701165
TI  - Lung Ultrasound Pattern Is Normal during the Last Gestational Weeks: An
      Observational Pilot Study.
AB  - BACKGROUND/AIMS: The normal lung ultrasound (US) pattern during a regular
      pregnancy has not been evaluated extensively in the current literature. Pregnancy
      related changes in the respiratory tract affect maternal predisposition to
      several respiratory complications; consequently, it is important to differentiate
      between a physiologic pattern during pregnancy and a pathologic lung pattern, due
      to respiratory failure. The goal of our study was to assess the normal US lung
      pattern in women without known comorbidities in the last weeks of pregnancy.
      METHODS: We conducted a prospective cross-sectional observational pilot study.
      Chest wall was examined in 8 areas, 1 scan for each area with women in supine
      position. RESULTS: One hundred fifty parturients were enrolled during the 36th
      38th gestational weeks. None of the participants showed pleural effusion,
      pneumothorax or lung consolidation. None presented an interstitial syndrome US
      pattern. One hundred thirteen participants out of 150 (75%) showed A-lines in all
      the regions. The remaining 25% showed 1 or 2 B-lines in at least 3 regions. Only
      2 participants showed 2 positive regions also. CONCLUSIONS: We found that, in the
      majority of the women examined, the lung US pattern matches the physiological
      pattern in non-pregnant patients. Lung US assessment is a feasible and a helpful
      diagnostic tool during pregnancy.

PMID- 27701166
TI  - Biomaterial Strategies for Delivering Stem Cells as a Treatment for Spinal Cord
      Injury.
AB  - Ongoing clinical trials are evaluating the use of stem cells as a way to treat
      traumatic spinal cord injury (SCI). However, the inhibitory environment present
      in the injured spinal cord makes it challenging to achieve the survival of these
      cells along with desired differentiation into the appropriate phenotypes
      necessary to regain function. Transplanting stem cells along with an instructive
      biomaterial scaffold can increase cell survival and improve differentiation
      efficiency. This study reviews the literature discussing different types of
      instructive biomaterial scaffolds developed for transplanting stem cells into the
      injured spinal cord. We have chosen to focus specifically on biomaterial
      scaffolds that direct the differentiation of neural stem cells and pluripotent
      stem cells since they offer the most promise for producing the cell phenotypes
      that could restore function after SCI. In terms of biomaterial scaffolds, this
      article reviews the literature associated with using hydrogels made from natural
      biomaterials and electrospun scaffolds for differentiating stem cells into neural
      phenotypes. It then presents new data showing how these different types of
      scaffolds can be combined for neural tissue engineering applications and provides
      directions for future studies.

PMID- 27701168
TI  - Serotonin as a Differentiation Signal.

PMID- 27701167
TI  - Metabolic and Hormonal Determinants of Glomerular Filtration Rate and Renal
      Hemodynamics in Severely Obese Individuals.
AB  - OBJECTIVE: Renal function is often compromised in severe obesity. A true
      measurement of glomerular filtration rate (GFR) is unusual, and how estimation
      formulae (EstForm) perform in such individuals is unclear. We characterized renal
      function and hemodynamics in severely obese individuals, assessing the
      reliability of EstForm. METHODS: We measured GFR (mGFR) by iohexol plasma
      clearance, renal plasma flow (RPF) by 123I-ortho-iodo-hippurate, basal and
      stimulated vascular renal indices, endothelium-dependent and -independent
      vasodilation using flow-mediated dilation (FMD) as well as metabolic and hormonal
      profile in morbid, otherwise healthy, obese subjects. RESULTS: Compared with
      mGFR, the better performing EstForm was CKD-EPI (5.3 ml/min/1.73 m2 bias by Bland
      Altman analysis). mGFR was directly related with RPF, total and incremental
      glucose AUC, and inversely with PTH and h8 cortisol. Patients with mGFR below the
      median shown significantly higher PTH and lower vitamin D3. Basal or dynamic
      renal resistive index, FMD, pulse wave velocity were not related with mGFR. In an
      adjusted regression model, renal diameter and plasma flow remained related with
      mGFR (R2 = 0.67), accounting for 15% and 21% of mGFR variance, respectively.
      CONCLUSIONS: CKD-EPI formula should be preferred in morbid obesity; glucose
      increments during oral glucose tolerance test correlate with hyperfiltration; RPF
      and diameter are independent determinants of mGFR; slightly high PTH values,
      frequent in obesity, might influence mGFR.

PMID- 27701169
TI  - Limited Time from the Diabetes Patients' Perspective: Need for Conversation with
      the Eye Specialist.
AB  - PURPOSE: Facing the lack of time, busy retina consultants should be aware of how
      the patients would prefer that time is spent and whether they wish the specialist
      to talk more at the expense of other medical activities. METHODS: 810 persons
      with diabetes were asked to divide the time of 10 min between examination,
      consultation and treatment when envisioning a real-life scenario of diabetic
      retinopathy (NCT02311504). RESULTS: With the increasing duration of diabetes,
      patients wanted significantly more time for diagnostics (p = 0.028), while age
      was found to be associated with less time for treatment (p = 0.009). Female
      subjects tended to prefer only little more time for talking (p = 0.051) in
      comparison with males, who slightly favored therapy (p = 0.025). CONCLUSIONS: The
      large majority recognized the need for diagnostics in their allocation of time.
      If individual patients are confronted with the health care perspective of time
      constraints, this might improve the understanding of prioritization.

PMID- 27701171
TI  - Preface.

PMID- 27701170
TI  - Pre-Stroke Use of Beta-Blockers Does Not Lower Post-Stroke Infection Rate: An
      Exploratory Analysis of the Preventive Antibiotics in Stroke Study.
AB  - BACKGROUND: Stroke-associated infections occur frequently and are associated with
      unfavorable outcome. Previous cohort studies suggest a protective effect of beta
      blockers (BBs) against infections. A sympathetic drive may increase immune
      suppression and infections. AIM: This study is aimed at investigating the
      association between BB treatment at baseline and post-stroke infection in the
      Preventive Antibiotics in Stroke Study (PASS), a prospective clinical trial.
      METHODS: We performed an exploratory analysis in PASS, 2,538 patients with acute
      phase of stroke (24 h after onset) were randomized to ceftriaxone (intravenous, 2
      g per day for 4 days) in addition to stroke unit care, or standard stroke unit
      care without preventive antibiotic treatment. All clinical data, including use of
      BBs, was prospectively collected. Infection was diagnosed by the treating
      physician, and independently by an expert panel blinded for all other data.
      Multivariable analysis was performed to investigate the relation between BB
      treatment and infection rate. RESULTS: Infection, as defined by the physician,
      occurred in 348 of 2,538 patients (14%). Multivariable analysis showed that the
      use of BBs at baseline was associated with the development of infection during
      clinical course (adjusted OR (aOR) 1.61, 95% CI 1.19-2.18; p < 0.01). BB use at
      baseline was also associated with the development of pneumonia (aOR 1.56, 95% CI
      1.05-2.30; p = 0.03). Baseline BB use was not associated with mortality (aOR
      1.14, 95% CI 0.84-1.53; p = 0.41) or unfavorable outcome at 3 months (aOR 1.10,
      95% CI 0.89-1.35; p = 0.39). CONCLUSIONS: Patients treated with BBs prior to
      stroke have a higher rate of infection and pneumonia.

PMID- 27701172
TI  - Engineering Biomaterials to Influence Oligodendroglial Growth, Maturation, and
      Myelin Production.
AB  - Millions of people suffer from damage or disease to the nervous system that
      results in a loss of myelin, such as through a spinal cord injury or multiple
      sclerosis. Diminished myelin levels lead to further cell death in which
      unmyelinated neurons die. In the central nervous system, a loss of myelin is
      especially detrimental because of its poor ability to regenerate. Cell therapies
      such as stem or precursor cell injection have been investigated as stem cells are
      able to grow and differentiate into the damaged cells; however, stem cell
      injection alone has been unsuccessful in many areas of neural regeneration.
      Therefore, researchers have begun exploring combined therapies with biomaterials
      that promote cell growth and differentiation while localizing cells in the
      injured area. The regrowth of myelinating oligodendrocytes from neural stem cells
      through a biomaterials approach may prove to be a beneficial strategy following
      the onset of demyelination. This article reviews recent advancements in
      biomaterial strategies for the differentiation of neural stem cells into
      oligodendrocytes, and presents new data indicating appropriate properties for
      oligodendrocyte precursor cell growth. In some cases, an increase in
      oligodendrocyte differentiation alongside neurons is further highlighted for
      functional improvements where the biomaterial was then tested for increased
      myelination both in vitro and in vivo.

PMID- 27701173
TI  - Inhibitory Control and Hedonic Response towards Food Interactively Predict
      Success in a Weight Loss Programme for Adults with Obesity.
AB  - OBJECTIVE: Low inhibitory control and strong hedonic response towards food are
      considered to contribute to overeating and obesity. Based on previous research,
      the present study aimed at examining the potentially crucial interplay between
      these two factors in terms of long-term weight loss in people with obesity.
      METHODS: BMI, inhibitory control towards food, and food liking were assessed in
      obese adults prior to a weight reduction programme (OPTIFAST(r) 52). After the
      weight reduction phase (week 13) and the weight loss maintenance phase (week 52),
      participants' BMI was re-assessed. RESULTS: Baseline BMI, inhibitory control and
      food liking alone did not predict weight loss. As hypothesised, however,
      inhibitory control and food liking interactively predicted weight loss from
      baseline to week 13 and to week 52 (albeit the latter effect was less robust).
      Participants with low inhibitory control and marked food liking were less
      successful in weight reduction. CONCLUSION: These findings underscore the
      relevance of the interplay between cognitive control and food reward valuation in
      the maintenance of obesity.

PMID- 27701174
TI  - Changes in Waist Circumference among German Adults over Time - Compiling Results
      of Seven Prospective Cohort Studies.
AB  - AIM: This study aims to quantify longitudinal changes in waist circumference (WC)
      among adults aged 45-64 years in Germany. METHODS: Data of 15,444 men and 17,207
      women from one nationwide and six regional prospective German cohort studies were
      analyzed. The sex-specific mean change in WC per year of follow-up was assessed
      for each study separately. Findings from the cohort-by-cohort analysis were
      combined by applying meta-analytic methods. Progression to central obesity (WC >=
      102 cm in men and >= 88 cm in women) within a standardized period of 10 years was
      described for each study. RESULTS: The estimated mean change in WC per year of
      follow-up for all cohorts combined was 0.53 (95% confidence interval 0.29-0.76)
      cm/year for men and 0.63 (0.48-0.77) cm/year for women, but varied between the
      included studies. Within 10 years, about 20% of individuals with low WC (<94 cm
      in men; <80 cm in women) and about 50% of individuals with intermediate WC (94
      102 cm in men; 80-88 cm in women) progressed to central obesity. CONCLUSION: The
      increase in mean WC with aging along with a profound increase of central
      adiposity is obviously and may have several adverse health effects. Obesity
      prevention programs should also focus on abdominal obesity.

PMID- 27701175
TI  - Evaluation of the Obesity Genes FTO and MC4R for Contribution to the Risk of
      Large Artery Atherosclerotic Stroke in a Chinese Population.
AB  - BACKGROUND: Obesity is a well-established risk factor for large artery
      atherosclerotic (LAA) stroke. The aim of the study was to explore whether obesity
      genes, such as MC4R and FTO, contribute to LAA stroke risk in the Chinese Han
      population. METHODS: 322 LAA stroke patients and 473 controls were recruited.
      Gene polymorphism of MC4R (rs17782313) and FTO (rs8050136 and rs9939609) were
      genotyped. RESULTS: No differences were observed in genotype frequencies of
      variants of FTO (rs8050136 and rs9939609) or MC4R (rs17782313) between LAA stroke
      patients and control subjects. However, rs17782313 of the MC4R gene was
      associated with LAA stroke susceptibility in smokers (rs17782313: p = 0.020, OR
      (95% CI) = 1.55 (1.07-2.23)) in the stratified analysis. Furthermore, multifactor
      dimensionality reduction analysis revealed that the combination of MC4R variant
      (rs17782313), hypertension and smoking habit was significantly associated with
      increased risk of LAA stroke (p < 0.0001, OR (95% CI) = 6.57 (4.79-9.01)).
      CONCLUSION: Our study indicated that the synergistic effects of MC4R variants,
      hypertension, and smoking habit contribute significantly to the risk of LAA
      stroke in the Chinese Han population. The finding revealed that obesity gene MC4R
      contribute to the risk of LAA stroke via a synergistic mechanism, which will
      provide new insight into the genetic architecture of LAA stroke.

PMID- 27701176
TI  - The Protective Effect of Febuxostat on Chronic Tacrolimus-Induced Nephrotoxicity
      in Rats.
AB  - BACKGROUND: The use of calcineurin inhibitors is a well-known risk factor for
      hyperuricemia in kidney transplant recipients. We evaluated the effect of
      febuxostat (Fx), a new uric acid-lowering drug, on hyperuricemia and renal injury
      in an experimental model of chronic tacrolimus (Tac)-induced nephropathy.
      METHODS: Chronic Tac nephropathy was induced by administering Tac (1.5 mg/kg/day)
      to rats on a low-salt diet (0.05%) with oxonic acid (OA, 2%, 0.2 g/kg/day) for 28
      days. Two doses of Fx (5 and 10 mg/kg) were concomitantly administered with Tac
      or vehicle (Vh). We evaluated the effect of Fx on hyperuricemia by measuring
      serum uric acid (SUA) levels, fractional excretion of uric acid (FEUA), and urate
      transporters in Tac-induced nephropathy. The effects of Fx on Tac-induced renal
      injury were evaluated in terms of renal function and arteriolopathy,
      tubulointerstitial fibrosis, inflammation, and apoptosis. We evaluated oxidative
      stress as a protective mechanism via xanthine oxidase (XO) activity, and as a
      marker of oxidative stress (via evaluation of levels of 8-hydroxy-2'
      deoxyguanosine (8-OHdG) and 4-hydroxy-2-hexenal (4-HHE)). RESULTS: The Tac group
      showed higher SUA levels and lower FEUA than did the Vh group, but Fx treatment
      significantly decreased SUA levels in a dose-dependent manner, with an increase
      of FEUA at a high dose (10 mg/kg). Tac treatment increased urate-anion exchanger
      1 and decreased organic anion transporter type 1 expression in renal tubular
      cells, but Fx treatment reversed the effects on those transporters. Impaired
      renal function and histological injury (interstitial fibrosis, inflammation, and
      arteriolopathy) in the Tac group were markedly improved by Fx administration.
      Increases in apoptotic cell death and activation of proapoptotic caspase-3 by Tac
      were remarkably decreased by Fx treatment. Tac administration increased the
      activity of XO in kidney tissue and serum, and the levels of 8-OHdG in urine and
      8-OHdG and 4-HHE of kidney tissue, but combined treatment with Fx decreased the
      levels of these parameters. CONCLUSIONS: Fx is effective in controlling
      hyperuricemia and in preventing Tac-induced renal injury, via a reduction of
      oxidative stress. Therefore, a targeted therapy aimed at inhibiting uric acid by
      Fx may be a useful approach in the management of the progression of nephropathy
      in renal transplant patients treated with Tac.

PMID- 27701177
TI  - Uremic Toxin-Producing Gut Microbiota in Rats with Chronic Kidney Disease.
AB  - BACKGROUND: In patients with chronic kidney disease (CKD), many metabolites of
      gut microbiota retain in the body as uremic toxins (UTs). However, the kinds of
      bacteria producing UTs are rarely discussed. METHODS: We analyzed UT production
      and the composition of gut microbiota in CKD rats and cecectomized rats. AST-120,
      a spherical carbon adsorbent, was administrated to evaluate how the precursors of
      UT affect gut microbiota. Serum and urine levels of UTs were quantified by liquid
      chromatography/electrospray ionization-tandem mass spectrometry. Gut microbiota
      were analyzed using 454-pyrosequencing of the 16S rRNA gene. Operational
      taxonomic unit (OTU) clustering and UniFrac analysis were performed to compare
      gut microbiota among the groups. RESULTS: Serum and urine levels of indoxyl
      sulfate and phenyl sulfate were higher in CKD versus control rats (p < 0.05). AST
      120 administration decreased UT production (p < 0.01) and changed overall gut
      microbiota composition in CKD rats. UT urinary excretion and gut microbiota
      composition changed in cecectomized rats, with the relative abundance of
      Clostridia- and Bacteroidia-affiliated species being significantly reduced (p <
      0.01). We identified candidate indole- and phenol-producing intestinal
      microbiota, 3 Clostridia, and 2 Bacteroidia. These OTUs have a
      tryptophanase/tyrosine phenol-lyase gene in the closest sequenced genome out of
      the OTUs declined following cecectomy. CONCLUSION: Our data suggest that UT
      production is correlated with a subset of indigenous gut microbiota. However, UT
      may be induced by other non-symbiotic microbiota that are influenced by factors
      other than microbiota populations. The relationship between specific microbiota
      and UTs in patients requires further clarification.

PMID- 27701178
TI  - Answers Regarding the Etiology of Severe Community-Acquired Pneumonia: Usefulness
      of Polymerase Chain Reaction Techniques.

PMID- 27701179
TI  - Parental Bonding and Dyadic Interaction: Source of Mental Health and Risk of
      Psychopathology.

PMID- 27701180
TI  - Bilateral Endoscopic Lung Volume Reduction in Patients with Severe Emphysema.
AB  - Reducing hyperinflated areas in chronic obstructive pulmonary disease, either
      surgically or endoscopically, leads to improvement of functional parameters. It
      is unclear if bilateral treatment with endobronchial valves (EBV) aiming at total
      lobar occlusion is beneficial. The aim of this study was to assess the results
      after staged bilateral endoscopic treatment with EBV. This is a retrospective
      analysis of patients with severe airflow obstruction, who were treated
      bilaterally with EBV in two stages, aiming at subsequent atelectasis. Pre- and
      postintervention lung function parameters, the 6-minute walk test (6-MWT),
      complications, and follow-up were recorded. Sixteen patients were treated
      bilaterally in two stages. There was an overall improvement in lung function from
      baseline to second-treatment follow-up with an increase in FEV1 (23.57-29.21% of
      predicted) and a decrease in residual volume (299.21-240.10% of predicted) and
      total lung capacity (140.78-128.71% of predicted). The 6-MWT improved up to 54 m.
      After each procedure, 9 of 16 patients (56.25%) developed an atelectasis of the
      target lobe. Overall, pneumothorax occurred in 8 of 32 procedures (25%). No
      patient died. Patients benefitted from the first EBV treatment. The second
      treatment did not lead to marked improvements compared to the first treatment.
      Bilateral lung volume reduction with valves is possible; however, the current
      results seem not to justify bilateral valve treatment as a routine approach.

PMID- 27701181
TI  - Deep-sea squat lobsters of the genus Paramunida Baba, 1988 (Crustacea: Decapoda:
      Munididae) from north-western Australia: new records and description of three new
      species.
AB  - Six species of Paramunida are reported from the continental margin of north
      western Australia. Three species are new to science: Paramunida christinae sp.
      nov., P. ioannis sp. nov., and P. spiniantennata sp. nov. Two species are
      reported for the first time from Australian waters, P. evexa Macpherson, 1996 and
      P. tricarinata (Alcock, 1894). These species were confirmed by molecular evidence
      from the mitochondrial markers ND1 and 16S. We also examine phylogenetic
      relationships within the genus, and provide an identification key for all known
      Paramunida species.

PMID- 27701182
TI  - Eidinemacheilus proudlovei, a new subterranean loach from Iraqi Kurdistan
      (Teleostei; Nemacheilidae).
AB  - Eidinemacheilus proudlovei, new species, is described from subterranean waters in
      the Little Zab River drainage in Iraqi Kurdistan. After the discovery of E.
      smithi in 1976, E. proudlovei is the second troglomorphic nemacheilid loach found
      in the Middle East and the second species placed in Eidinemacheilus.
      Eidinemacheilus proudlovei is distinguished from E. smithi by having 8+8 or 8+7
      branched caudal-fin rays, no adipose keel on the caudal peduncle, enlarged jaws
      and a fully developed head canal system. It furthers differs substantially in its
      DNA barcode (>8% K2P distance) from all other nemacheilid loaches in the Middle
      East, Europe and Western India.

PMID- 27701183
TI  - On the identity of some poorly known species of the genus Endonura Cassagnau,
      1979 (Collembola, Neanuridae, Neanurinae).
AB  - New data on little known species of the genus Endonura are provided. E.
      transcaucasica (Stach, 1951), from Georgia, is redescribed in details and its
      lectotype is designated. E. centaurea (Cassagnau & Peja, 1979) and E. deharvengi
      (Cassagnau & Peja, 1979), both described from Greece, are redescribed and
      illustrated based on type material for the first time. Redescription of E. caeca
      (Gisin, 1963), a taxon known only from the type locality in Bosnia and
      Herzegovina, is given based on holotype.

PMID- 27701184
TI  - A unique new genus and species of the phyline plant bug tribe Hallodapini from
      the Philippines and Thailand (Hemiptera: Heteroptera: Miridae: Phylinae:
      Hallodapini).
AB  - A unique phyline plant bug representing a new genus and a new species,
      Peniculimiris meniscus, is documented on the basis of a pair of specimens
      collected from Nakhon Ratchasima, central Thailand and Palawan, the Philippines.
      The new genus Peniculimiris, herein placed in the tribe Hallodapini, is
      characteristic in having a bundle of brush-like, stiff setae on the scutellum and
      presence of a ventral spine on the genital segment of each sex. The phylogenetic
      position of Peniculimiris in the Hallodapini and the function of the spines are
      discussed.

PMID- 27701185
TI  - Update of the genus Leptochiton (Mollusca: Polyplacophora) in Chilean deep
      waters: three new reports and description of two new species.
AB  - We update the list of the bathyal chitons of the genus Leptochiton inhabiting
      Chilean waters. We report new records of Leptochiton belknapi and L. laurae, the
      first record of L. sigwartae for the area and the new species L. ibanezi sp. nov.
      and L. ferreirai sp. nov. With 12 species, including those described herein as
      new, the highest species richness of Leptochiton is found in Chilean deep waters.
      Taking into consideration the potential late Paleozoic origin of the genus
      Leptochiton, we propose that Leptochiton originated in the old Pacific Ocean and
      migrated to the young Atlantic Ocean. However, the genus has also been considered
      non-monophyletic.

PMID- 27701186
TI  - Physoschistura walongensis, a new species of loach (Teleostei: Nemacheilidae)
      from Arunachal Pradesh, northeastern India.
AB  - Physoschistura walongensis, new species, is described from the bank of the Lohit
      River (upper Brahmaputra River basin) in the eastern most part of the state
      Arunachal Pradesh at an altitude of 1096 m above sea level. The new species is
      distinguished from its congeners by the following combination of characters: an
      incomplete lateral line extending at least to the anal-fin origin and maximally
      to the tip of the adpressed anal fin, with 71-89 canal pores; a rounded
      suborbital flap, the posterior margin of which slightly exceeds the anterior
      orbital margin, occupying less orbital area; body with 11-18 irregular vertical
      bars on the flank, bars more irregular on the anterior portion of the body than
      on posterior; 1-4 bars bifurcate ventrally; 1-4 saddles along the ventrolateral
      side of the body; a moderately thick W-shaped basicaudal bar; a prominent
      axillary pelvic fin lobe; dark brown mottled markings on the head; and forked
      caudal fin with 9 upper + 8 lower branched rays.

PMID- 27701187
TI  - Grammatonotus brianne, a new callanthiid fish from Philippine waters, with short
      accounts of two other Grammatonotus from the Coral Triangle.
AB  - In May 2014, a group of ichthyologists from the California Academy of Sciences
      and the Bishop Museum collecting fishes off the coast of Batangas, Luzon,
      Philippine Islands, obtained, in a depth of ca. 150 meters, four specimens of a
      species of Grammatonotus previously unknown to science. This new species,
      Grammatonotus brianne, is distinguishable from its described congeners by the
      following combination of characters: short anal-fin spines, rhomboid shaped
      caudal fin, lateral line usually disjunct, and live coloration. Herein we provide
      characters that distinguish callanthiids from other percoids and that distinguish
      Grammatonotus from Callanthias, the other genus in the family Callanthiidae,
      along with the description of the new species and short accounts of two other
      Grammatonotus, G. crosnieri and G. roseus, from the Coral Triangle.

PMID- 27701188
TI  - Pseudochromis yamasakii, new species of dottyback fish from Japan (Teleostei:
      Pseudochromidae: Pseudochrominae).
AB  - Gill (2004) recognised fifty-seven species in the Indo-Pacific genus
      Pseudochromis Ruppell (1835) but noted that the genus is undiagnosed
      cladistically and effectively serves as a catch-all for species that can't be
      placed in other pseudochromine genera (sensu Gill 2013). Since publication of
      Gill's revision, 13 additional species of Pseudochromis have been described,
      mostly based on recent collections from the highly diverse Coral Triangle area of
      the West Pacific (Gill & Allen 2004, 2011; Allen et al. 2008; Gill et al. 2009,
      2012a,b; Gill & Williams 2011; Gill & Zajonz 2011; Allen & Erdmann 2012). We
      herein describe an additional new species, which is known on the basis of a
      single specimen from Kii Peninsula, Honshu, Japan, and from several photographs
      from the Kii Peninsula and Izu Islands, Japan.

PMID- 27701189
TI  - Taxonomic observations on stingrays of the genus Dasyatis (Chondrichthyes:
      Dasyatidae) in the Gulf of Gabes (Southeastern Mediterranean Sea).
AB  - Four species of stingrays of the genus Dasyatis occur in the Gulf of Gabes, but
      the taxonomic status of one of them, D. tortonesei has been questioned by several
      authors, and synonymized with D. pastinaca by some. The present study, using
      morphological comparisons and genetic analyses, demonstrates that there is a
      closely related species to D. pastinaca in the Gulf of Gabes, but distinguishable
      by several characters. This species is provisionally identified as Dasyatis cf.
      tortonesei, pending a more extensive comparative study including specimens from
      other regions of the Mediterranean Sea and eastern North Atlantic Ocean.

PMID- 27701190
TI  - A new species of Pisionidens (Aiyar & Alikunhi, 1943) (Annelida: Sigalionidae)
      from Southeastern Brazil.
AB  - Herein we describe specimens found along the southeastern coast of Brazil which
      belong to a new species, P. caissara sp. nov. This species differs from the other
      species of the genus by the glabrous antennae and palps, proboscis extending up
      to the sixth segment, jaws with smooth cutting edge and a pair of lateral wing
      like sheaths, two pairs of seriate male copulatory organs, first pair of testes
      on segment 19 and ovaries from segment 26 onward. Reproductive characters
      commonly used for characterizing species are also discussed.

PMID- 27701191
TI  - A review of the genus Minthodes Brauer & Bergenstamm (Diptera: Tachinidae) in
      Iran, with the description of a new species.
AB  - Minthodes susae Gilasian & Ziegler sp. nov. (Diptera: Tachinidae), from
      southwestern Iran, is described and illustrated, and compared with M. brevipennis
      (Brauer & Bergenstamm) from Turkey. A lectotype is recognised for Pseudomintho
      brevipennis Brauer & Bergenstamm (currently a species of Minthodes) and its
      designation is attributed to Mesnil. Minthodes pictipennis Brauer & Bergenstamm
      is newly recorded from Iran and Turkey, and M. latifacies Herting is reported
      from Iran for the first time. An identification key to the four Minthodes Brauer
      & Bergenstamm species known to occur in Iran is provided. Finally, new data are
      given on the intraspecific variation of Minthodes atra (Kugler).

PMID- 27701192
TI  - New species of tree cricket Oecanthus Serville, 1831 (Orthoptera: Gryllidae:
      Oecanthinae) from Reserva Natural Vale, Espirito Santo, Brazil, with chromosome
      complement.
AB  - A new species of the genus Oecanthus Serville, 1831 from Reserva Natural Vale,
      state of Espirito Santo, Brazil is described. The new species differs from other
      of this genus in characteristics of the pseudepiphallus main lobe, endophallic
      sclerites, posterior median lobe of the metanotal gland and black spots on the
      femora and tibiae. The chromosome number is 2n=16+XY?=18 and 2n=16+XX?=18, and
      this complement present one pair of autosomes less than the other five
      cytological studied species.

PMID- 27701193
TI  - Establishment of a new genus for Abraximorpha heringi and A. pieridoides <br
      />(Lepidoptera: Hesperiidae: Pyrginae: Tagiadini).
AB  - A new hesperiid genus, Albiphasma gen. nov., is described with Abraximorpha
      heringi as the type species. The new genus consists of two species: Al. heringi
      comb. nov. and Al. pieridoides comb. nov. The genitalia and hair tuft on the hind
      tibiae suggest that the new genus is related to the genus Pintara rather than the
      genus Abraximorpha to which the two species have been assigned. The geographic
      distribution is currently restricted to southern China and Vietnam. The adult,
      hind leg, wing venation and male genitalia of Al. heringi as well as relevant
      species are illustrated.

PMID- 27701194
TI  - Redescription of two Ctenidae (Araneae) from Taiwan.
AB  - Two ctenid species, Anahita maolan Zhu, Chen & Song, 1999 and Ctenus yaeyamensis
      Yoshida, 1998 from Taiwan are redescribed in detail based on both sexes. Anahita
      maolan is reported from Taiwan for the first time. For both species, Kenting
      National Park (southernmost Taiwan) is the southernmost known locality.

PMID- 27701195
TI  - Microscydmus trianguliceps Franz and Pseudoeudesis sulcata Franz transferred to
      Afroeudesis Franz (Coleoptera: Staphylinidae: Scydmaeninae).
AB  - Afroeudesis Franz was described as a subgenus of Pseudoeudesis Binaghi
      (Scydmaenini), with a single species from Tanzania. Recently, Afroeudesis was
      transferred to Glandulariini and elevated to generic rank, and the sub-Himalayan
      Nanoscydmus Jaloszynski was reduced to a subgenus of Afroeudesis. New surprising
      findings concerning Afroeudesis are presented here, extending the known
      geographic range of this enigmatic genus. Microscydmus trianguliceps Franz (Ivory
      Coast) and Pseudoeudesis sulcata Franz (SE Brazil) are transferred to
      Afroeudesis, each to a newly established subgenus: Eburneus subgen. n. and
      Eudesoides subgen. n., respectively. Afroeudesis (Eburneus) trianguliceps comb.
      n. and Afroeudesis (Eudesoides) sulcata comb. n. are redescribed. The genus name
      Eudesis is interpreted here as feminine; consequently Afroeudesis (Nanoscydmus)
      baoshanus is corrected to baoshana. The disjunct and possibly relict Gondwanan
      distribution of Afroeudesis is discussed.

PMID- 27701196
TI  - Two new Pediopsis species and a new Ruandopsis species (Hemiptera: Cicadellidae:
      Macropsinae) from Madagascar.
AB  - Three new species, Pediopsis tripartita, P. subtilis and Ruandopsis elongata spp.
      nov., from Madagascar are described. These species represent the first records of
      their respective genera in Madagascar. Images of adults and genitalia of the
      three species are provided.

PMID- 27701197
TI  - Three unusual species of Erythroneurini (Hemiptera: Cicadellidae) with
      description of new genera.
AB  - Two new genera of the leafhopper tribe Erythroneurini, Nedotepa gen. n. and
      Alerrawia gen. n., and three new species, Nedotepa curta sp. n. from Ghana,
      Alerrawia meliae sp. n. from Kenya, and Musbrnoia linnavuorii sp. n. from
      Indonesia, are described and illustrated. Nedotepa curta sp. n. has an unusually
      reduced ovipositor, a feature not previously recorded in Typhlocybinae. Musbrnoia
      linnavuorii sp. n. has extremely elongated parts of the male terminalia, which
      remarkably resemble parts of the female ovipositor.

PMID- 27701198
TI  - Physoschistura chhimtuipuiensis, a new species of loach (Teleostei:
      Nemacheilidae) from Mizoram, north-eastern India.
AB  - Physoschistura chhimtuipuiensis, new species, from a tributary of the Kaladan
      River in Mizoram, northeastern India, is distinguished from all other species of
      Physoschistura by a combination of the following characters: scales between
      pectoral- and pelvic-fin bases deeply embedded and sparsely set, lateral line
      incomplete with 56-63 pores, reaching slightly beyond the base of the last anal
      fin ray, a suborbital flap in male, 81/2 branched dorsal-fin rays and 8+7
      branched caudal-fin rays.

PMID- 27701199
TI  - On Blaps Fabricius, 1775 (Coleoptera: Tenebrionidae) from Western Kazakhstan with
      description of a new species from Tyuleniy Archipelago (Caspian Sea).
AB  - A new species of darkling beetles Blaps caspica sp. n. from Western Kazakhstan
      Kulaly Island (Tyuleniy Archipelago, Caspian Sea) is described. This new taxon
      belongs to the 6<sup>th</sup> group of the 2<sup>nd</sup> section according to
      Seidlitz's classification and is most similar to Blaps kadyrbekovi G. Medvedev,
      2004, B. lethifera Marsham, 1802 and B. parvicollis Zoubkoff, 1829. Blaps caspica
      sp. n. differs from B. kadyrbekovi by the presence of a hair tuft between male
      abdominal ventrites 1 and 2, from B. parvicollis by having narrow acute short
      spurs on the mesotibiae, the structure of the gastral spicula, ovipositor and
      female genital tubes, from B. lethifera by the slender elliptic body, punctated
      (not granulated) epipleura and the structure of the female genital tubes. Images,
      an identification key and local distribution are given for ten Western Kazakhstan
      species of the genus Blaps Fabricius, 1775.

PMID- 27701200
TI  - Two new species of Papuagrion Ris, 1913 (Odonata: Coenagrionidae) from New Guinea
      with a survey of distribution records for the genus.
AB  - Two new species of Papuagrion Ris, 1913 are described from Papua Province,
      Indonesia. These are P. marirobi sp .nov. from Japen Island and P. stellimontanum
      sp .nov., from the Star Mountains. The new species are, respectively, most
      closely allied to P. degeneratum Lieftinck and P. digitiferum Lieftinck. They
      bring the number of Papuagrion species to 28. New locality records of several
      other species are noted.

PMID- 27701201
TI  - The first riparian skink (Genus: Sphenomorphus Strauch, 1887) from Peninsular
      Malaysia and its relationship to other Indochinese and Sundaic species.
AB  - Recently discovered populations of skinks of the genus Sphenomorphus from central
      Peninsular Malaysia represent a new species, S. sungaicolus sp. nov., and the
      first riparian skink known from Peninsular Malaysia. Morphological analyses of an
      earlier specimen reported as S. tersus from the Forest Research Institute of
      Malaysia (FRIM), Selangor indicate that it too is the new riparian species S.
      sungaicolus sp. nov. Additionally, two specimens from the Tembat Forest Reserve,
      Hulu Terengganu, Kelantan and another from Ulu Gombak, Selangor have been
      diagnosed as new the species. The latter specimen remained unidentified in the
      Bernice Pauahi Bishop Museum, Honolulu, Hawaii since its collection in June 1962.
      Morphological and molecular analyses demonstrate that S. sungaicolus sp. nov.
      forms a clade with the Indochinese species S. maculatus, S. indicus, and S.
      tersus and is the sister species of the latter. Sphenomorphus sungaicolus sp.
      nov. can be differentiated from all other members of this clade by having a
      smaller SVL (66.5-89.6 mm); 39-44 midbody scale rows; 72-81 paravertebral scales;
      74-86 ventral scales; a primitive plantar scale arrangement; and 20-22 scale rows
      around the tail at the position of the 10<sup>th</sup> subcaudal.

PMID- 27701202
TI  - A new South American Miocene species of 'one-holed' sand dollar (Echinoidea:
      Clypeasteroida: Monophorasteridae).
AB  - A new species of monophorasterid sand dollar, Monophoraster telfordi n. sp., is
      described from the Early Miocene basal horizons of the Chenque Formation of
      Patagonia, Santa Cruz Province, in southern Argentina. The new taxon raises the
      number of known species in the family to six, and represents first unequivocal
      record of the genus for the Early Miocene of South America. It is therefore also
      the oldest member of the genus. M. telfordi is characterized by its test width to
      length ratio, which is much higher than for the other two described species in
      the genus, but less than that known for the extremely wide members of the sister
      taxon, Amplaster. M. telfordi is also unusual among monophorasterids in lacking
      broad continuity between basicoronal and post-basicoronal plates in the oral
      interambulacra. A key is provided to all the known species of Monophorasteridae.

PMID- 27701203
TI  - Validity and Redescription of Profundulus balsanus Ahl, 1935 (Cyprinodontiformes:
      Profundulidae).
AB  - Profundulus balsanus was described by Ahl in 1935 and later placed in synonymy
      with P. punctatus. Recent molecular studies have demonstrated that specimens
      identified as P. balsanus belong to a distinct taxon. Herein we used a
      combination of morphometric, meristic, coloration and osteological data in order
      to demonstrate the distinctiveness of P. balsanus. Additionally, we used
      molecular data to reconstruct a phylogeny to place P. balsanus in a systematic
      context. Profundulus balsanus belongs to the punctatus clade within the genus
      Profundulus. It can be distinguished from P. oaxacae based on scale count in the
      lateral line and from P. punctatus based on differences in coloration in the anal
      fin. We provide a taxonomic key to all Mexican species of Profundulus.

PMID- 27701204
TI  - New genus and species of ant-like true bug (Hemiptera: Miridae) from the Canary
      Islands.
AB  - Perenotus gen. nov. is described based on males and females from the Canary
      Islands, Spain. This new genus is easily recognized by having a myrmecomorphic
      appearance and a scutellar hump in both sexes. Systellonotus stysi J. Ribes,
      Pagola-Carte et Heiss, 2008, was described based on females collected in Tenerife
      and La Palma, but careful examination showed that specimens from each island
      belong to different species, and can be transferred to the new genus Perenotus. 
      As a result, Perenotus includes two species, P. stysi comb. n. for specimens from
      Tenerife and P. malobae sp. nov. for specimens from La Palma. In the present
      publication Perenotus gen. nov. and P. malobae sp. nov. are described, P. stysi
      female is redescribed, and P. stysi male is described for the first time.
      Illustrations of male and female general habitus and genitalia are provided.

PMID- 27701205
TI  - On the nature of Scleropages leichardti Gunther, 1864 (Pisces: Osteoglossidae).
AB  - The Australasian Saratoga (Pisces: Osteoglossidae) is currently recognised as
      comprised of two species Scleropages leichardti and S. jardinii. The Prussian
      explorer Ludwig Leichhardt (1813-c.1848) collected specimens of both species on
      his first major expedition across northern Australia but believed at the time
      that all specimens collected were from within one species. Details of the fate of
      these specimens are unclear as is the geographic origin of those specimens that
      ultimately made their way into museum collections. Gunther's 1864 description of
      the Southern Saratoga S. leichardti, purportedly from the Fitzroy River in
      Queensland to which it is restricted (although he erred and listed it as the
      Burdekin River) is meagre and inconsistent with contemporary accounts of the
      morphology of this species. It is also inconsistent with a subsequent description
      by de Castelnau in 1876 of the supposedly synonymous Osteoglossum guntheri.
      Finally, the description of S. leichardti by Gunther is largely consistent with
      meristic and morphometric information within Saville-Kent's (1892) description of
      the wide-spread Northern Saratoga S. jardinii. On balance, these inconsistencies,
      doubt about the provenance and geographic origin of type material and provenance
      of the original descriptions all strongly suggest that Gunther based his
      description of S. leichardti on material collected from within the range of the
      more widespread taxon currently recognised as S. jardinii. A revision of the
      Australian species within the genus Scleropages is warranted.

PMID- 27701206
TI  - Synchiropus sycorax, a new species of dragonet from the Philippines (Teleostei:
      Callionymidae).
AB  - Synchiropus sycorax n. sp. is described from six specimens (22.6-40.1 mm SL)
      collected from Jolo Island, Sulu Archipelago, Philippines. It appears to be most
      closely related to S. tudorjonesi, which ranges from the Maldive Islands through
      Indonesia and the Philippine Islands to southern Japan. The new species differs
      from S. tudorjonesi and other congeners in live coloration: head and body bright
      red, bright yellow ventrally, with prominent white spots on head (one spot or
      blotch over preopercular spine, two elongate spots behind middle of eye, and one
      spot behind upper part of eye at about 1 o'clock position) and body (in three
      rows, an uppermost row beginning below soft dorsal, tracking lateral line to
      caudal peduncle, a lowermost row extending from above anterior anal fin to caudal
      peduncle, and a middle row extending obliquely from above pectoral fin to
      anterior part of lowermost series of spots); males with pelvic fin and pelvic
      pectoral membrane bright yellow with broad bluish or greenish grey to black
      submarginal band across distal third of fin.

PMID- 27701207
TI  - A new genus of freshwater crab of the tribe Kingsleyini Bott, 1970 (Crustacea:
      Decapoda: Brachyura: Pseudothelphusidae) with description of a new species from
      Mato Grosso, Brazil.
AB  - A new genus and species of freshwater crab, Melothelphusa apiaka n. gen., n. sp.,
      from Mato Grosso, Central Brazil is described and illustrated. Brasiliothelphusa
      dardanelosensis Magalhaes & Turkay, 2010, is assigned to the new genus
      Melothelphusa. Therefore, the genus Brasiliothelphusa Magalhaes & Turkay, 1986,
      is restricted to its type species B. tapajoense Magalhaes & Turkay, 1986. The new
      taxa can be easily separated from their close relatives by a suite of
      morphological characters from the first gonopod.

PMID- 27701208
TI  - Nomenclatural Studies Toward a World List of Diptera Genus-Group Names. Part V:
      Pierre-Justin-Marie Macquart.
AB  - The Diptera genus-group names of Pierre-Justin-Marie Macquart are reviewed and
      annotated. A total of 399 available genus-group names in 69 families of Diptera
      are listed alphabetically, for each name giving author, year and page of original
      publication, originally included species, type species and method of fixation,
      current status of the name, family placement, and a list of any emendations of it
      that have been found in the literature. Remarks are given to clarify
      nomenclatural or taxonomic information. In addition, an index to all the species
      group names of Diptera proposed by Macquart (3,611, of which 3,543 are available)
      is given with bibliographic reference (year and page) to each original citation.
      The following type species are designated herein: Agculocera nigra Macquart, 1855
      for Onuxicera Macquart, 1855, present designation [Tachinidae]; Trixa imhoffi
      Macquart, 1834, for Semiomyia Macquart, 1848, present designation [Tachinidae].
      The following type species are designated herein with fixation under ICZN Code
      Art. 70.3.2: Azelia nebulosa Robineau-Desvoidy, 1830 for Atomogaster Macquart,
      1835, present designation [Muscidae]; Tachydromia vocatoria Fallen, 1816 for
      Chelipoda Macquart, 1835, present designation [Empididae]; Eriocera macquarti
      Enderlein, 1912 for Eriocera Macquart, 1838, present designation [Limoniidae];
      Limosina acutangula Zetterstedt, 1847 for Heteroptera Macquart, 1835, present
      designation [Sphaeroceridae]; Phryxe pavoniae Robineau-Desvoidy, 1830 for
      Masicera Macquart, 1834, present designation [Tachinidae]; Pachymyia macquartii
      Townsend, 1916 for Pachymyia Macquart, 1844, present designation [Tachinidae].
      Earlier valid subsequent type-species designations have been found in this study
      for the following: Anisophysa Macquart, 1835 [Sepsidae]; Diphysa Macquart, 1838
      [Stratiomyidae]; Pachyrhina Macquart, 1834 [Tipulidae]; Silbomyia Macquart, 1844
      [Calliphoridae]. One name is raised from synonymy: Czernyola Bezzi, 1907, n.
      stat. [Clusiidae]. Names previously treated as available but found in this work
      to be unavailable include the following: Genus-group names-Anodontina Macquart,
      1838, n. stat. [Empididae]; Athricia Macquart, 1834, n. stat. [Tachinidae];
      Blepharis Macquart, 1838, n. stat. [Asilidae]; Dichelocera Enderlein, 1922, n.
      stat. [Tabanidae]; Lepidoselaga Loew, 1869, n. stat. [Tabanidae]; Lemptopeza
      Macquart, 1828, n. stat. [Hybotidae]; Microphora Zetterstedt, 1842, n. stat.
      [Dolichopodidae]; Microphorus Macquart, 1834, n. stat. [Dolichopodidae];
      Plagiocephala Macquart, 1844, n. stat. [Ulidiidae]; Stratiomyia Macquart, 1838,
      n. stat. [Stratiomyidae]; Taenioptera Agassiz, 1846, n. stat. [Micropezidae];
      Tapigaster Bezzi, 1923, n. stat. [Heleomyzidae]; Trizota Macquart, 1829, n. stat.
      [Syrphidae]. Species-group names-Microstylum sinense Macquart, 1838, n. stat.
      [Asilidae]. Corrected or clarified included species and/or corrected or clarified
      type-species and methods of typification are given for: Anabarhynchus Macquart,
      1848 [Therevidae]; Anacanthella Macquart, 1855 [Stratiomyidae]; Apeilesis
      Macquart, 1846 [Tipulidae]; Aplomera Macquart, 1838 [Empididae]; Aprotheca
      Macquart, 1851 [Tachinidae]; Ardoptera Macquart, 1828 [Empididae]; Blepharella
      Macquart, 1851 [Tachinidae]; Brachystylum Macquart, 1855 [Tachinidae]; Cadicera
      Macquart, 1855 [Tabanidae]; Calobatemyia Macquart, 1855 [Calliphoridae];
      Catapicephala Macquart, 1851 [Calliphoridae]; Ceroptera Macquart, 1835
      [Sphaeroceridae]; Cheligaster Macquart, 1835 [Sepsidae]; Chetogaster Macquart,
      1851 [Tachinidae]; Chlorogaster Macquart, 1851 [Tachinidae]; Cleitamia Macquart,
      1835 [Platystomatidae]; Craspedia Macquart, 1838 [Asilidae]; Craspedochoeta
      Macquart, 1851 [Anthomyiidae]; Crumomyia Macquart, 1835 [Sphaeroceridae];
      Dasyomma Macquart, 1840 [Athericidae]; Demoticus Macquart, 1854 [Tachinidae];
      Epicerella Macquart, 1851 [Pyrgotidae]; Epicerina Macquart, 1850 [Acroceridae];
      Euprosopia Macquart, 1847 [Platystomatidae]; Grapholostylum Macquart, 1851
      [Tachinidae]; Graphomyzina Macquart, 1835 [Sciomyzidae]; Gymnostylina Macquart,
      1835 [Tachinidae]; Heterometopia Macquart, 1846 [Tachinidae]; Laxenecera
      Macquart, 1838 [Asilidae]; Leptomyza Macquart, 1835 [Anthomyzidae]; Megistogaster
      Macquart, 1851 [Tachinidae]; Microtrichodes Macquart, 1846 [Tachinidae];
      Microtropesa Macquart, 1846 [Tachinidae]; Ogcodocera Macquart, 1840
      [Bombyliidae]; Onuxicera Macquart, 1855 [Tachinidae]; Ozodicera Macquart, 1834
      [Tipulidae]; Pachymerina Macquart, 1834 [Empididae]; Pachyrhina Macquart, 1834
      [Tipulidae]; Pachystylum Macquart, 1848 [Tachinidae]; Physegaster Macquart, 1847
      [Acroceridae]; Plesionevra Macquart, 1855 [Tachinidae]; Rhopalia Macquart, 1838
      [Mydidae]; Semiomyia Macquart, 1848 [Tachinidae]; Senostoma Macquart, 1847
      [Tachinidae]; Silbomyia Macquart, 1844 [Calliphoridae]; Sumpigaster Macquart,
      1855 [Tachinidae]; Tapinocera Macquart, 1838 [Apioceridae]; Teretrophora
      Macquart, 1851 [Tachinidae]; Toxocnemis Macquart, 1855 [Tachinidae]; Toxotarsus
      Macquart, 1851 [Calliphoridae]; Trichostylum Macquart, 1851 [Tachinidae];
      Trigonometopus Macquart, 1835 [Lauxaniidae]; Tritaxys Macquart, 1847
      [Tachinidae]; Vermileo Macquart, 1834 [Vermileonidae]. Acting as First Reviser,
      the following correct original spellings for multiple original spellings are
      selected by us-(for genus-group names): Choeteprosopa Macquart, 1851
      [Tachinidae]; Dichoetometopia Macquart, 1855 [Sarcophagidae]; Discocerina
      Macquart, 1835 [Ephydridae]; Dolichocephala Macquart, 1823 [Empididae];
      Dolichomerus Macquart, 1850 [Syrphidae]; Graphalostylum Macquart, 1851
      [Tachinidae]; Hemilampra Macquart, 1850 [Syrphidae]; Leptomyza Macquart, 1835
      [Anthomyzidae]; Microcheilosia Macquart, 1855 [Tachinidae]; Phrissopodia
      Macquart, 1835 [Sarcophagidae]; Platytainia Macquart, 1851 [Tachinidae];
      Polychaeta Macquart, 1851 [Tachinidae]; Stachynia Macquart, 1835 [Conopidae]-(for
      species-group names): Cadicera rubramarginata Macquart, 1855 [Tabanidae].
      Previous First Reviser actions for multiple original spellings that were missed
      by other workers are given for the following: Amethysa Macquart, 1835
      [Ulidiidae]; Anabarhynchus Macquart, 1848 [Therevidae]; Anacanthella Macquart,
      1855 [Stratiomyidae]; Aulacigaster Macquart, 1835 [Aulacigastridae]; Cardiacera
      Macquart, 1847 [Pyrgotidae]; Comptosia Macquart, 1840 [Bombyliidae]; Craspedia
      Macquart, 1838 [Asilidae]; Cyclorhynchus Macquart, 1840 [Bombyliidae];
      Ectinorhynchus Macquart, 1850 [Therevidae]; Euthinevra Macquart, 1836
      [Hybotidae]; Gonistylum Macquart, 1851 [Tachinidae]; Heterostylum Macquart, 1848
      [Bombyliidae]; Hoplistomera Macquart, 1838 [Asilidae]; Hystricephala Macquart,
      1846 [Tachinidae]; Leptoxyda Macquart, 1835 [Tephritidae]; Nemopalpus Macquart,
      1838 [Psychodidae]; Senotainia Macquart, 1846 [Sarcophagidae]; Spilogaster
      Macquart, 1835 [Muscidae]; Spogostylum Macquart, 1840 [Bombyliidae]; Stachynia
      Macquart, 1835 [Conopidae]. Invoking ICZN Code Article 33.3.1, the following is
      here considered a correct original spelling by being in prevailing usage:
      Leptopeza Macquart, 1828 [Empididae]. Reversal of Precedence (ICZN Code Article
      23.9) is invoked to promote stability in nomenclature for the following cases of
      subjective synonymy: Atherigona Rondani, 1856, nomen protectum and Orthostylum
      Macquart, 1851, nomen oblitum [in Muscidae]; Clusiodes Coquillett, 1904, nomen
      protectum and Heteronevra Macquart, 1835, nomen oblitum [in Clusiidae];
      Senotainia Macquart, 1846, nomen protectum and Megoera Macquart, 1834, nomen
      oblitum [in Sarcophagidae]. The following genus-group names, not listed in
      current regional catalogs, are treated here: Diasema Macquart, 1835
      [Chloropidae]; Dichromyia Macquart, 1844 [Heleomyzidae]; Elomyia Macquart, 1834
      [Tachinidae]; Eriosoma Macquart, 1838 [Acroceridae]; Eurypalpus Macquart, 1835
      [Platystomatidae]; Notacanthina Macquart, 1835 [Ephydridae]; Pleurocerina
      Macquart, 1851[Conopidae]; Pteropexus Macquart, 1846 [Acroceridae]; Semiomyia
      Macquart, 1848 [Tachinidae]; Teremyia Macquart, 1835 [Lonchaeidae]. The following
      names are new synonymies of their respective senior synonyms: -genus-group names:
      Acemyia Macquart, 1834 of Acemya Robineau-Desvoidy, 1830, n. syn. [Tachinidae];
      Acrochoeta Macquart, 1835 of Acrochaeta Wiedemann, 1830, n. syn. [Stratiomyidae];
      Atractea Agassiz, 1846 of Atractia Macquart, 1838, n. syn. [Asilidae];
      Aulacocephala Brauer, 1863 of Aulacephala Macquart, 1851, n. syn. [Tachinidae];
      Beckeriella Williston, 1897 of Notacanthina Macquart, 1834, n. syn. [Ephydridae];
      Caenosia Macquart, 1835 of Coenosia Meigen, 1826, n. syn. [Muscidae]; Ceromyia
      Macquart, 1834 of Ceromya Robineau-Desvoidy, 1830, n. syn. [Tachinidae];
      Chiromysa Macquart, 1835 of Chiromyza Wiedemann, 1820, n. syn. [Stratiomyidae];
      Chrisochlora Macquart, 1835 of Chrysochlora Latreille, 1829, n. syn.
      [Stratiomyidae]; Chrysopyla Macquart, 1840 of Chrysopilus Macquart, 1826, n. syn.
      [Rhagionidae]; Cleigaster Macquart, 1844 of Cleigastra Macquart, 1835, n. syn.
      [Scathophagidae]; Clyto Macquart, 1835 of Clytho Robineau-Desvoidy, 1830, n. syn.
      [Tachinidae]; Cordylura Macquart, 1835 of Cordilura Fallen, 1810, n. syn.
      [Scathophagidae]; Craspedochaeta Marschall, 1873 of Anthomyia Meigen, 1803, n.
      syn. [Anthomyiidae]; Cyrtonevra Agassiz, 1846 of Graphomya Robineau-Desvoidy,
      1830, n. syn. [Muscidae]; Diaphora Macquart, 1834 of Diaphorus Meigen, 1824, n.
      syn. [Dolichopodidae]; Dichoeta Macquart, 1835 of Dichaeta Meigen, 1830, n. syn.
      [Ephydridae]; Dichromyia Macquart, 1844 of Dichromya Robineau-Desvoidy, 1830, n.
      syn. [Heleomyzidae]; Diphysa Macquart, 1838 of Archistratiomys Enderlein, 1913,
      n. syn. [Stratiomyidae]; Echinomyia Fischer von Waldheim, 1808 of Tachina Meigen,
      1803, n. syn. [Tachinidae]; Egina Macquart, 1835 of Eginia Robineau-Desvoidy,
      1830, n. syn. [Muscidae]; Hematobia Macquart, 1850 of Haematobia Le Peletier &
      Audinet-Serville, 1828, n. syn. [Muscidae]; Hemerodromyia Macquart, 1823 of
      Hemerodromia Meigen, 1822, n. syn. [Empididae]; Heteronevra Macquart, 1835 of
      Clusiodes Coquillett, 1904, n. syn. [Clusiidae]; Himastima Agassiz, 1846 of
      Mallota Meigen, 1822, n. syn. [Syrphidae]; Hoematopota Macquart, 1826 of
      Haematopota Meigen, 1803, n. syn. [Tabanidae]; Homalocephala Agassiz, 1846 of
      Setellia Robineau-Desvoidy, 1830, n. syn. [Sciomyzidae]; Hydrotoea Macquart, 1844
      of Hydrotaea Robineau-Desvoidy, 1830, n. syn. [Muscidae]; Linnemyia Macquart,
      1834 of Linnaemya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Lonchoea
      Macquart, 1835 of Lonchaea Fallen, 1820b, n. syn. [Lonchaeidae]; Macromyia
      Macquart, 1835 of Macromya Robineau-Desvoidy, 1830, n. syn. [Tachinidae];
      Megarhina Macquart, 1838 of Lynchiella Lahille, 1904, n. syn. [Culicidae];
      Meriana Macquart, 1835 of Panzeria Robineau-Desvoidy, 1830, n. syn. [Tachinidae];
      Microphorus Lundbeck, 1907 of Microphor Macquart, 1834, n. syn. [Dolichopodidae];
      Nemoroea Macquart, 1844 of Nemoraea Robineau-Desvoidy, 1830, n. syn.
      [Tachinidae]; Ochthiphila Macquart, 1850 of Chamaemyia Meigen, 1803, n. syn.
      [Chamaemyiidae]; Ocydromyia Macquart, 1823 of Ocydromia Meigen, 1820, n. syn.
      [Hybotidae]; Oliviera Macquart, 1835 of Eriothrix Meigen, 1803, n. syn.
      [Tachinidae]; Ophilia Macquart, 1850 of Metopia Meigen, 1803, n. syn.
      [Sarcophagidae]; Ornithomyia Fischer von Waldheim, 1808 of Ornithomya Latreille,
      1802, n. syn. [Hippoboscidae]; Orthochile Westwood, 1840 of Ortochile Latreille,
      1809, n. syn. [Dolichopodidae]; Osmoea Macquart, 1834 of Triarthria Stephens,
      1829, n. syn. [Tachinidae]; Pachyrrhina Osten Sacken, 1878 of Pachyrhina
      Macquart, 1834, n. syn. [Tipulidae]; Palis Macquart, 1850 of Pales Robineau
      Desvoidy, 1830, n. syn. [Tachinidae]; Phanemia Macquart, 1835 of Clairvillia
      Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Phrissopoda Macquart, 1851 of
      Peckia Robineau-Desvoidy, 1830, n. syn. [Sarcophagidae]; Phyllomyia Macquart,
      1834 of Phyllomya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Physogenia Loew,
      1862 of Physegenua Macquart, 1848, n. syn. [Lauxaniidae]; Physogenua Giglio-Tos,
      1895 of Physegenua Macquart, 1848, n. syn. [Lauxaniidae]; Phytomiza Macquart,
      1835 of Phytomyza Fallen, 1810, n. syn. [Agromyzidae]; Platipalpus Macquart, 1850
      of Platypalpus Macquart, 1828, n. syn. [Hybotidae]; Platipeza Macquart, 1850 of
      Platypeza Meigen, 1803, n. syn. [Platypezidae]; Platynochoetus Macquart, 1834 of
      Platynochaetus Wiedemann, 1830 [Syrphidae]; Porphirops Macquart, 1838 of
      Porphyrops Meigen, 1824, n. syn [Dolichopodidae]; Rhinomyia Macquart, 1835 of
      Rhinomya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Rhynomyia Macquart, 1834
      of Rhinomya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Scathopse Guerin
      Meneville, 1839 of Scatopse Geoffroy, 1762, n. syn. [Scatopsidae]; Spherophoria
      Macquart, 1850 of Sphaerophoria Le Peletier & Audinet-Serville, 1828, n. syn.
      [Syrphidae]; Sphoerophoria Macquart, 1829 of Sphaerophoria Le Peletier & Audinet
      Serville, 1828, n. syn. [Syrphidae]; Stenopteryx Schiner, 1864 of Stenepteryx
      Leach, 1817, n. syn. [Hippoboscidae]; Stenostoma Mik, 1890 of Senostoma Macquart,
      1847, n. syn. [Tachinidae]; Tachydromyia Macquart, 1823 of Tachydromia Meigen,
      1803, n. syn. [Hybotidae]; Taenioptera Mik, 1898 of Taeniaptera Macquart, 1835,
      n. syn. [Micropezidae]; Trinevra Macquart, 1835 of Phora Latreille, 1797, n. syn.
      [Phoridae]; Uramyia Macquart, 1844 of Uramya Robineau-Desvoidy, 1830, n. syn.
      [Tachinidae]; Xestomysa Macquart, 1851 of Xestomyza Wiedemann, 1820, n. syn.
      [Therevidae]; Zygonevra Macquart, 1834 of Zygoneura Meigen, 1803, n. syn.
      [Sciaridae]. -Species-group names: Calobatemyia nigra Macquart, 1855 of Musca
      doronici Scopoli, 1763, n. syn. [Calliphoridae]; Cyrtonevra protorum Macquart,
      1850 of Musca pratorum Meigen, 1826, n. syn. [Muscidae]; Eumerus oeneus Macquart,
      1850 of Eumerus aeneus Macquart, 1829, n. syn. [Syrphidae]; Lucilia ceserion
      Macquart, 1850 of Musca caesarion Scharfenberg, 1805, n. syn. [Calliphoridae];
      Masicera sylvatica Macquart, 1850 of Tachina silvatica Fallen, 1810, n. syn.
      [Tachinidae]; Ophyra anolis Macquart, 1850 of Ophyra analis Macquart, 1846, n.
      syn. [Muscidae]; Pegomyia hyosciami Macquart, 1850 of Musca hyoscyami Panzer,
      1798, n. syn. [Anthomyiidae]; Prosena syberita Macquart, 1850 of Stomoxys
      siberita Fabricius, 1775, n. syn. [Tachinidae]; Taxigramma heteronevra Macquart,
      1850 of Miltogramma heteroneura Meigen, 1830, n. syn. [Sarcophagidae].

PMID- 27701209
TI  - Illustrated and online catalog of type specimens of freshwater fishes in the
      Coleccion de Peces Dulceacuicolas of Instituto de Investigacion de Recursos
      Biologicos Alexander von Humboldt (IAvH-P), Colombia.
AB  - The catalog of type specimens of freshwater fishes deposited in the Coleccion de
      Peces Dulceacuicolas del Instituto de Investigacion de Recursos Biologicos
      Alexander von Humboldt (IAvH-P) is presented. This list includes 483 specimens in
      65 lots representing 11 holotypes and 472 paratypes of 48 nominal species.
      Corrections, additions, and updating of information in the original descriptions
      are included in individual remarks for each catalog number entry and a gallery of
      pictures of holotypes or paratypes of each nominal species is also presented,
      which supplements some original descriptions lacking figures of their respective
      types. An online version of the catalog is available at
      http://humboldt.org.co/en/servicios/colecciones-biologicas/catalogo-de-tipos.

PMID- 27701210
TI  - A new species of Ituglanis (Siluriformes: Trichomycteridae) from the Tocantins
      and Paranaiba river basins, central Brazil, with remarks on the systematics of
      the genus.
AB  - Ituglanis goya, new species, is described from the Paranaiba and Tocantins river
      drainages, central Brazil. This is the first species of the genus described for
      the Upper Parana system and the second epigean Ituglanis for the Tocantins basin.
      The new species is distinguished from its congeners by the combination of a color
      pattern formed by longitudinal stripes and spots, absence of the anterior cranial
      fontanel, pattern of the cephalic laterosensory system and several fin-ray
      counts. Ituglanis goya exhibits morphological features that oppose the
      traditional hypotheses of alignment of the genus with the TSVSG clade of
      Trichomycteridae. These and other issues concerning the systematics of Ituglanis
      and the Trichomycterinae are critically discussed.

PMID- 27701211
TI  - Two new species of Pasipha Ogren & Kawakatsu (Platyhelminthes: Continenticola)
      from areas of deciduous forest in southern Brazil.
AB  - Two new species of Geoplaninae from southern Brazil are described herein. The new
      species, belonging to the genus Pasipha Ogren & Kawakatsu, 1990, can be
      distinguished from each other and from their congeners by colour pattern and
      characteristics of the copulatory apparatus, especially regarding the female
      organs and prostatic vesicle. Both new species seem to be endemic to areas
      covered by deciduous forest.

PMID- 27701212
TI  - Ultramorphological characteristics of unknown larva of Phloeonomus punctipennis
      Thomson, 1867 (Coleoptera; Staphylinidae; Omaliinae): an obligate saproxylic
      species: notes on chaetotaxy and ecological preferences.
AB  - The aim of the study was to describe the morphological ultrastructure, including
      chaetotaxy, of the previously unknown early (L<sub>1</sub>) and late (L<sub>2
      3</sub>) larval instars of Phloeonomus punctipennis. The diagnostic larval
      characters for the genus Phloeonomus are proposed for the first time.
      Morphological differences between L<sub>1</sub> and L<sub>3</sub> refer only to
      the proportion of length of individual parts of antennae and legs as well as
      length proportion of urogomphi and their subapical setae. The chaetotaxy of the
      mature larvae of P. punctipennis and Dalotia coriaria, as a model of aleocharine
      larvae, is compared. Despite some identified differences, the chaetotaxic system
      proposed previously for Aleocharinae is successfully applied to the larva of P.
      punctipennis. It may most probably be also useful for larvae of other Omaliinae
      species. Also, information on geographical distribution and the ecological
      preferences of this species is provided, as is the information on accompanying
      insects.

PMID- 27701213
TI  - Idiocnemis schorri sp. nov., a new damselfly species from southern Papua New
      Guinea (Odonata: Platycnemididae).
AB  - Idiocnemis schorri sp. nov. is described from the Hindenburg and Muller Ranges
      and the Kikori River Basin of southern Papua New Guinea. The new species differs
      from all congeners by, among other characters, a unique colour pattern on the
      thorax. Characters of males and females are illustrated and compared to those of
      similar species from the Idiocnemis bidentata group. The new species is found
      along small, shallow rainforest streams and is currently known only from the
      Trans-Fly Foreland and Papuan Gulf Foreland areas of endemism.

PMID- 27701214
TI  - Description of a new Penaeidae (Decapoda: Dendrobranchiata) species,
      Farfantepenaeus isabelae sp. nov.
AB  - The pink shrimp, Farfantepenaeus subtilis, actually comprises two cryptic species
      confused under a single name. Despite morphological and molecular evidences
      accumulated since 1967, the new species confused with F. subtilis has never been
      formally described. In this paper, Farfantepenaeus isabelae sp. nov., is
      described and compared to its close relatives, F. brasiliensis, F. notialis, F.
      paulensis and F. subtilis s. str..

PMID- 27701215
TI  - Taxonomic notes on the genus Tiliacea Tutt, 1896 (Lepidoptera, Noctuidae,
      Xylenini) with the description of a new species and a new genus.
AB  - The updated checklist and a general characterisation of the species-groups of the
      genus Tiliacea are presented. ''Xanthia yunnana'' Chen, 1999 syn. nov. is moved
      from the genus Tiliacea and synonymised with Gortyna joannisi (Boursin, 1928).
      One new species, Tiliacea annamaria sp. n. is described. ''Xanthia'' aurantiago
      (Draudt, 1950) is combined into the genus Tiliacea comb. nov. and a new genus,
      Tuttiana gen. nov. is established for ''Xanthia'' xanthophylla (Hreblay & Ronkay,
      1998) comb. nov. and ''Cirrhia'' spalvota (Benedek & Saldaitis, 2011) comb. nov.

PMID- 27701216
TI  - Retrocitomyia Lopes, 1982 (Diptera: Sarcophagidae): new species, new records, key
      to males, and an updated catalog.
AB  - Prior to this work, Retrocitomyia Lopes (Diptera: Sarcophagidae) included ten
      recognized species distributed exclusively in the New World. We here add a new
      species to the genus, Retrocitomyia sisbiota sp. nov. from the Central-West
      Region of Brazil. Four other species of Retrocitomyia are recorded from this
      region for the first time, redescribed, compared, and illustrated, with emphasis
      on the male terminalia. Retrocitomyia paraguayensis Lopes is recorded from Brazil
      for the first time, R. fluminensis Lopes and R. retrocita (Hall) are newly
      recorded from the Brazilian states of Mato Grosso and Mato Grosso do Sul, and R.
      mizuguchiana Tibana & Xerez is newly recorded from the state of Mato Grosso do
      Sul. New generic diagnostic characters are added and the interpretation of some
      structures of the male terminalia is discussed. An updated catalog of all
      Retrocitomyia species and an identification key to the males of these species are
      also provided.

PMID- 27701217
TI  - The phylogeny of marine sculpins of the genus Icelinus with comments on the
      evolution and biogeography of the Pseudoblenninae.
AB  - The marine sculpins (Psychrolutidae) are a diverse percomorph family with notable
      morphological variation and repeated biogeographic patterns within the group. The
      psychrolutid genus Icelinus is unusual because it is one of the few near-shore
      members of the family that exhibits a trans-Pacific distribution; it has two
      species in the western Pacific and nine species in the eastern Pacific.
      Furthermore, the placement of Icelinus has been more inconsistent across
      molecular and morphological analyses than many genera. Previous phylogenetic
      studies have hypothesized sister taxa to Icelinus ranging from Antipodocottus,
      Chitonotus, and Stlengis, to a mixed clade of psychrolutids. The varied
      placements across these studies may be due to limited taxon sampling within
      Icelinus, and previous authors have never included western Pacific species of
      Icelinus in their analyses. This study tests the monophyly of the genus, examines
      the relationships between eastern and western Pacific species of Icelinus, and
      explores the relationships of Icelinus within Psychrolutidae. Our results show
      that the traditional grouping of Icelinus is polyphyletic. The eastern Pacific
      species of Icelinus are restricted to a clade sister to Furcina and
      Antipodocottus. The western Pacific species of Icelinus are recovered sister to
      the genus Stlengis. Given the polyphyly of Icelinus, the sister-group pairing of
      western Pacific species of Icelinus and Stlengis, as well as morphological
      similarity between the two groups, we recommend treating the western Pacific
      species of Icelinus as members of the genus Stlengis. With this taxonomic change,
      species in the genus Icelinus are now limited to the eastern Pacific, ranging
      from Alaska to Mexico.

PMID- 27701218
TI  - Three new species of glass sponges Pheronematidae (Porifera: Hexactinellida) from
      the deep-sea of the northwestern Pacific Ocean.
AB  - Three new glass sponge species of the family Pheronematidae are described in this
      study. Specimens were sampled in the northwestern Pacific Ocean during cruise
      DY125-35I expedition (July-August, 2014) conducted by the China Ocean Mineral
      Resources R&D Association. All samples were collected by the Chinese manned
      submersible Jiaolong HOV at a depth of 1627-2897 m. The three species belonging
      to three genera of the same family were observed, i.e., Platylistrum subviridum
      sp. nov. Poliopogon canaliculatus sp. nov. and Semperella retrospinella sp. nov.
      An unique form of the pinular ray of pinular pentactins with reclined spines is
      described for S. retrospinella sp. nov. This is also the first record of
      Platylistrum in the Pacific Ocean.

PMID- 27701219
TI  - New species and records of Microveliinae and Veliinae (Hemiptera: Heteroptera:
      Veliidae) from Colombia.
AB  - Euvelia orinoquia sp. nov. and E. meta sp. nov. from eastern Colombia are
      described, illustrated, and included in an updated identification key to the
      species of the genus. The former can be diagnosed by body length 2.30-2.50 mm,
      male fore femur without tufts of setae, longitudinal black stripe of female
      pronotum almost twice as wide as length of antennomere I, and female connexiva
      grayish black with silvery pruinosity on mesal portion, reddish on lateral
      portion. Euvelia meta sp. nov. can be diagnosed by female body length about 1.50
      mm and maximum body width 0.90 mm, patches of silvery setae on female abdominal
      terga II-III and V-VII, and connexival segments I and IV-VI. Additionally, new
      records from the country are presented for species of Euvelia Drake, Husseyella
      Herring, Microvelia Westwood (Microveliinae), Oiovelia Drake & Maldonado
      Capriles, Platyvelia Polhemus & Polhemus, Stridulivelia Hungerford, and Veloidea
      Gould (Veliinae).

PMID- 27701220
TI  - A new species of Rhagovelia Mayr, 1865 (Hemiptera: Heteroptera: Veliidae) from
      Para State, with an updated key to Brazilian species of the robusta group.
AB  - Rhagovelia brunae Magalhaes & Moreira sp. nov., collected in the State of Para,
      Brazil, is described, illustrated, and compared with congeners. The new species
      belongs to the robusta group and can be differentiated from others by the general
      color black, abdominal sternum VII with black denticles laterally, male hind
      trochanter with 1-4 subequal spines plus a longer spine, and male hind femur
      lacking a medium spine between the proximal and distal rows of spines.
      Additionally, an updated identification key to species of the robusta group
      occurring in Brazil is presented.

PMID- 27701221
TI  - Status of the names of some hydroid species (Cnidaria, Hydrozoa), described from
      the Atlantic coast of Patagonia.
AB  - Thirty new species of benthic leptothecate hydroids were described and named from
      Patagonia in a 1991 PhD dissertation by Mohamed El Beshbeeshy. Although
      constituting nomina nuda under provisions of the International Code of Zoological
      Nomenclature (ICZN), the names of some species were used in several scientific
      publications between 1991 and 2011. In 2011, the dissertation of El Beshbeeshy
      was published in accordance with Article 8 of the ICZN. Several species-group
      names appearing in that work nevertheless fail to fully comply with certain
      articles of the code. The goal of this contribution is to review the
      nomenclatural availability of the names of those 30 new taxa, and to clearly
      establish the current status of El Beshbeeshy's material. Two of them were made
      available in 1999 as part of studies other than those of El Beshbeeshy, and
      correct authorship and date is here noted. Twenty-one of the nomina nuda were
      made available in a work published by El Beshbeeshy in 2011, although some
      constitute junior synonyms. Six of the new species-group names appearing in both
      the 1991 and 2011 works, established following a literature review of Patagonian
      species, were proposed without re-description, or designation of name-bearing
      types, or locations of such types. Most of them do not meet criteria of
      availability and remain nomina nuda. The status of each is discussed to avoid
      additional nomenclatural errors and continued taxonomic confusion.

PMID- 27701222
TI  - Taxonomy and immature stages of the Platystomatidae (Diptera: Tephritoidea) of
      Israel.
AB  - The Platystomatidae fauna of Israel is reviewed. Eleven species in two genera,
      Platystoma Meigen and Rivellia Robineau-Desvoidy, are recognized. Ten of the
      eleven species are recorded from Israel for the first time, and six of them are
      described as new: Platystoma dalia n. sp., P. elizabethae n. sp., P. geula n.
      sp., P. torridum n. sp., P. trigonum n. sp., and Rivellia israelica n. sp.
      Detailed descriptions, redescriptions, illustrations, and keys to all local
      platystomatid taxa are provided. The complete life-cycle of P. torridum n. sp. is
      reported, with descriptions and illustrations of egg, 3<sup>rd</sup> instar
      larva, and puparium.

PMID- 27701223
TI  - Two new troglobiotic palpigrades (Palpigradi: Eukoeneniidae) from Brazil.
AB  - Two new species of troglobiotic Brazilian palpigrades are described: Eukoenenia
      jequitinhonha sp. n., found in Lapa do Corrego do Vieira cave (Carai, Minas
      Gerais) and E. cavatica sp. n., found in Cazanga cave (Arcos, Minas Gerais). The
      importance of documenting the occurrence of troglobiotic species, even if they
      are represented by only a single specimen, is discussed.

PMID- 27701224
TI  - Some representative species of the tribe Holochlorini (Orthoptera: Tettigoniidae:
      Phaneropterinae) and the description of two new species from India.
AB  - In the present paper two new species of the genus Holochlora (Phaneropterinae:
      Holochlorini) have been described viz., Holochlora umranensis sp. nov., collected
      from Meghalaya, the North-eastern province, India (Ri bhoi 90 degrees 55'15 to 91
      degrees 16' latitude and 25 degrees 40' to 25 degrees 21' longitude, 993 MSL) and
      Holochlora alsigarhensis sp. nov., collected from Southern-western, Rajasthan,
      (Udaipur N 24 34'17 to E 73 41' 30'' and Latitude 24.5713, Longitude 73.6915, 582
      MSL), as additions to the previously known species of the genus that were earlier
      collected from the southern parts of India. Among these, four species are being
      reported for the first time from India including: H. brevifissa, H. fruhstorferi,
      H. japonica and Rectimarginalis profunda Liu & Kang. The key morphological
      characters of the head, pronotum, tenth abdominal tergite, subgenital plate,
      cerci, titillator and the ovipositor have been illustrated with suitable line
      drawings to distinguish the known, reported and new species, along with a key to
      the genera and species.

PMID- 27701226
TI  - Two new species of Stenaelurillus Simon, 1886 from India (Araneae: Salticidae:
      Aelurillina).
AB  - Stenaelurillus digitus sp. nov. and Stenaelurillus gabrieli sp. nov. are
      described from India. New distributional records for Stenaelurillus albus
      Sebastian et al., 2015 and Stenaelurillus lesserti Reimoser, 1934 and maps for
      these species are given.

PMID- 27701225
TI  - A revision and key for the tribe Diaphorolepidini (Serpentes: Dipsadidae) and
      checklist for the genus Synophis.
AB  - The genus Synophis contains a number of enigmatic species, distributed primarily
      in the Andean highlands of northern South America. Their extreme crypsis and
      rarity has precluded detailed study of most species. A recent flurry of
      collection activity resulted in the accession of many new specimens, and the
      description of 4 new species in 2015, doubling the number of described taxa.
      However, lingering questions remain regarding the assignment of many new and
      historical specimens, the morphological limits and geographical ranges of the
      species, and their phylogenetic relationships. We analyze new and existing
      morphological and molecular data to produce a new molecular phylogeny and revised
      morphological descriptions. We validate the previously unavailable tribe name
      Diaphorolepidini Jenner, Pyron, Arteaga, Echevarria, & Torres-Carvajal tribe
      nov., describe a 9th species Synophis niceforomariae Pyron, Arteaga, Echevarria,
      & Torres-Carvajal sp. nov., and offer new Standard Names in English and Spanish
      for the group: Andean Shadow Snakes and Culebras Andinas de la Sombra,
      respectively. A variety of features such as vertebrae and hemipenes show an
      interesting range of variation in the group, which should be evaluated in future
      studies, to refine species limits and diagnoses further. Cryptic and undiscovered
      diversity undoubtedly remains, and we hope this summary provides a robust basis
      for future work.

PMID- 27701227
TI  - Peristedion richardsi sp. nov. (Actinopterygii: Teleostei: Peristediidae) from
      Indonesian waters, with synonymy between Peristedion riversandersoni Alcock, 1894
      and Peristedion nierstraszi Weber, 1913.
AB  - A new armored searobin, Peristedion richardsi sp. nov., is described on the basis
      of three specimens collected from the deep sea (485-600 m) off Java, Indonesia.
      This new species differs from the Indo-West Pacific congeners in having anterior
      edge of the 4th sensory pore of the rostral projection located anterior to the
      anterior edge of the premaxilla, perifacial rim prominent starting near anterior
      margin of lower jaw, spatulate rostral projection with very narrow interspace
      between both rostral projections, rostral projection width 1.33-1.73 in
      interspace between both rostral projections, and rostral projection with straight
      margin on medial side at base. It is clear that Peristedion nierstraszi Weber,
      1913 is a junior synonym of Peristedion riversandersoni Alcock, 1894. In
      addition, a lectotype is designated for P. nierstraszi.

PMID- 27701228
TI  - New species and new records of genus Rhyacophila Pictet (Trichoptera:
      Rhyacophilidae) from Dabie Mountains, east-central China.
AB  - Three new species of Rhyacophila, Rhyacophila longiramata n. sp., Rhyacophila
      haplostephanodes n. sp., and Rhyacophila brevitergata n. sp., from the Dabie
      Mountains of east-central China, are described and illustrated. Rhyacophila
      longiramata n. sp. and R. haplostephanodes n. sp. both are highly specialized,
      which makes them very difficult to be put in any existing species group. Possible
      positions for these two species are discussed. Rhyacophila brevitergata n. sp.
      belongs to the R. nigrocephala Species Group. Rhyacophila spp. from Dabie
      Mountains are listed.

PMID- 27701229
TI  - Contribution to knowledge of Typhlocybinae (Hemiptera: Cicadellidae) in Thailand:
      first record of genus Arboridia Zachvatkin with description of three new species
      and a new synonymy.
AB  - Three new species, Arboridia (Arboridia) magna sp.nov., A. (Arborifera) mira
      sp.nov. and A. (Arboridia) sexprocessa sp.nov. from Phitsanulok, Thailand are
      described and illustrated. A key for the identification of species of Arboridia
      from Thailand is provided. Arboridia (Arboridia) koreana Oh & Jung 2015 is
      synonymised with A. (Arboridia) agrillacea (Anufriev 1969).

PMID- 27701230
TI  - A new and endangered species of Kingsleya Ortmann, 1897 (Crustacea: Decapoda:
      Brachyura: Pseudothelphusidae) from Ceara, northeastern Brazil.
AB  - A new species of freshwater crab, Kingsleya attenboroughi n. sp., from the
      Arajara district, Ceara state, Brazil, is described and illustrated. The new
      species differs from congeners by having a short apical plate in the first
      gonopod, with anteriorly directed lobes and proximally angular; proximal lobe of
      the apical plate with conspicuous semicircular protuberance in mesial and sternal
      views; marginal process protruded, projecting mesially in sternal view and
      subquadrate in mesial view; and field of apical spines narrow, tapering distally,
      with small spines concentrated proximally. Opportunity is taken to illustrate K.
      gustavoi Magalhaes, 2005, the closest allied species of K. attenboroughi n. sp. A
      key for the species of Kingsleya Ortmann, 1897 is provided.

PMID- 27701231
TI  - Leptobasis linda sp. nov. from Ecuador (Odonata: Coenagrionidae).
AB  - Leptobasis linda is described from the Pacific lowlands of Ecuador. The
      coloration of mature individuals is superficially similar to the widespread L.
      vacillans, but structural and color characteristics differentiate L. linda from
      all congeneric species. The male caudal appendages and the female posterior
      margin of the prothorax are unique among Leptobasis.

PMID- 27701232
TI  - Leptogomphus tioman sp. nov. (Odonata: Anisoptera: Gomphidea) from Tioman Island,
      Peninsular Malaysia.
AB  - A new species Leptogomphus tioman is described based on male specimens collected
      from Tioman Island, Peninsular Malaysia. It is close to Leptogomphus risi Laidlaw
      in thoracic markings but is readily distinguished by its anal appendages and
      accessory genitalia.

PMID- 27701233
TI  - One new species of the genus Acosmetura (Tettigoniidae: Meconematinae) from
      Hubei, China.
AB  - One new species of the genus Acosmetura (Tettigoniidae: Meconematinae) is
      described, namely Acosmetura trigentis Wang, Bian & Shi sp. nov. from Hubei,
      China. In addition, morphological photographs and a distribution map are
      provided. The examined specimens are deposited in the Museum of Hebei University.

PMID- 27701234
TI  - The identity of the Carsidara species (Hemiptera: Psylloidea: Carsidaridae)
      associated with Firmiana simplex (Malvaceae) in Japan and Korea.
AB  - The records of the jumping plant-lice previously published under Carsidara
      shikokuensis (Miyatake, 1981) from Japan and C. marginalis Walker, 1869 from
      Korea are critically reviewed. It is concluded that both refer to the same
      species that is associated with Firmiana simplex (L.) W.Wight (Malvaceae).
      Carsidara shikokuensis shows no relevant morphological differences to C. limbata
      (Enderlein, 1926), and the two are synonymised: Carsidara limbata (Enderlein,
      1926) = Carsidara shikokuensis (Miyatake, 1981) syn. nov. A record of C.
      marginalis from Korea is a misidentification of C. limbata. The latter is
      diagnosed and illustrated and differences to the former are discussed. The
      immatures of C. limbata are free-living on the leaves of Firmiana simplex and
      particularly the older instars secrete large amounts of flocculent wax and
      honeydew. Information on its potential usage as biological control agent of
      invasive Firmiana simplex in North America is briefly discussed.

PMID- 27701235
TI  - Morphology and COI barcodes reveal four new species in the lycieus group of
      Calisto (Lepidoptera, Nymphalidae, Satyrinae).
AB  - The predominantly Greater Antillean endemic genus Calisto Hubner, 1823 is highly
      diversified on several islands being more species rich on Hispaniola. We
      conducted expeditions during five years in the Dominican Republic resulting in
      new findings related with lyceius species group. Material belonging to this group
      was examined following the traditional morphological characters employed in genus
      taxonomy, and the COI barcode sequences obtained were analyzed through different
      approaches: Neighbor Joining clustering, ABGD, Maximum Likelihood (ML), and
      Bayesian Inference (BI). Analysis yielded 12 groups representing putative
      species: eight corresponding to previously named ones and four new species which
      are described in the present work: C. mariposa sp. nov., C. azua sp. nov., C.
      victori sp. nov., and C. samana sp. nov. The results also confirmed a single
      taxonomic entity within C. pulchella Lathy and the conspecific nature of C.
      franciscoi Gali and C. hendersoni. A dichotomic key for identification of species
      within the group is also given. Both phylogenetic reconstruction methods (ML and
      BI) employing molecular data achieved similar results with the relationships
      among the majority of taxa being supported by some ecological and morphological
      features. The exceptions were C. zangis Fabricius, C. raburni Gali, and C.
      pulchella, grouped together in a weakly supported clade. These species possess a
      highly differentiated adult and immature morphology which indicates an earlier
      divergence.

PMID- 27701236
TI  - Amphipoda (Crustacea) from Palau, Micronesia: Families Maeridae and Melitidae.
AB  - Seven species of senticaudate amphipods belonging to the families Maeridae and
      Melitidae are recorded from Palau, Federated States of Micronesia, and are
      figured. Three species are new to science and are fully described and figured.

PMID- 27701237
TI  - Review of subterranean Quedius, with description of the first hypogean species
      from the Russian Far East (Coleoptera: Staphylinidae: Staphylinini).
AB  - Hypogean species of Quedius, one of the largest North Hemisphere beetle genera,
      are reviewed in connection with the discovery of a new peculiar, brachypterous
      and microphtalmous species from the subgenus Microsaurus in the talus-based
      microhabitats of the Russian Far East. Morphology of that species here described
      as Quedius roma sp. n. suggests its affinity with the przewalskii-group from
      China and Nepal. Affinity of Q. roma to the abnormalis-group, a geographically
      more proximate and species-rich and presumably non-monophyletic assemblage of
      hypogean species from Japan and Taiwan, or to any other Holarctic Microsaurus is
      not supported morphologically. Two hypogean species from Europe, Q. bernhaueri
      Rambousek, 1915 and Q. doderoi Gridelli, 1922, are transferred from the subgenus
      Microsaurus to the subgenus Raphirus. The name Tenebrobius Rambousek, 1915, a
      subgenus where Q. bernhaueri was originally described, becomes a junior synonym
      of Raphirus Stephens, 1829.

PMID- 27701238
TI  - An annotated checklist of the New World pentodontine scarab beetles (Coleoptera:
      Scarabaeidae: Dynastinae: Pentodontini).
AB  - An updated and annotated checklist of the Pentodontini (Coleoptera: Scarabaeidae:
      Dynastinae) of the New World is presented. The tribe is composed of 32 genera and
      151 species, including the introduced species Heteronychus arator (Fabricius).

PMID- 27701239
TI  - New species of Thelepodidae (Terebelliformia, Polychaeta) from Taiwan.
AB  - Four new species of thelepodid polychaetes are reported from Taiwan, Streblosoma
      chiguensis sp. nov., Streblosoma wuchiensis sp. nov., Thelepus taiwanensis sp.
      nov., Thelepus longtongensis sp. nov. The family Thelepodidae, as well as the two
      genera Streblosoma and Thelepus, is reported for the first time from Taiwanese
      waters. A synoptic table, including number of branchial filaments on segments 2
      to 4, the presence/absence of eyespots, number of pairs of notopodia, uncinial
      dental formula of anterior and posterior tori, and type locality, is provided for
      all species of Thelepus.

PMID- 27701240
TI  - A new species of Amolops (Anura: Ranidae) from southern China.
AB  - A new species, Amolops albispinus sp. nov. is described based on a series of
      specimens collected from Mt. Wutong, Shenzhen, Guangdong Province, China. The new
      species can be distinguished from other known congeners by molecular divergence
      in the mitochondrial COI and 16S rRNA gene and morphological characters including
      presence of white conical spines on the lips, loreal and temporal regions,
      excluding the tympanum; small body, SVL 36.7-42.4 mm in adult males and 43.1-51.9
      mm in adult females; very rough dorsal skin of body with numerous raised large
      warts; olive-brown dorsum with dark brown blotches; strongly developed vomerine
      teeth; absence of vocal sacs; absence of tarsal glands; absence of dorsolateral
      folds; presence of circummarginals groove on the disk of first finger; and
      absence of outer metatarsal tubercles. At present, the genus Amolops contains 51
      species, of which 23 occur in China.

PMID- 27701241
TI  - Wrapped in flames: Corydoras hephaestus, a new remarkably colored species from
      the Rio Madeira basin (Teleostei: Callichthyidae).
AB  - A new species of Corydoras is described from the upper Rio Machado, Rio Madeira
      basin, Rondonia State, Brazil. The new species can be distinguished from its
      congeners by the absence of contact between the posterior process of the parieto
      supraoccipital and the nuchal plate; a ventral laminar expansion of the
      infraorbital 1 conspicuously developed; and the posterior margin of the pectoral
      fin spine with serrations along almost of its entire length, only lacking in the
      distal portion. Additionally, Corydoras hephaestus possesses dorsal and pectoral
      spines short, and exhibits an unusual color pattern in life. The conservation
      status of the new species and other endemic species are briefly commented.

PMID- 27701242
TI  - Contributions to the knowledge of the biodiversity of Heteroptera (Insecta) in
      the Southern Cone, Argentina.
AB  - Insect studies for different regions are scarce as most of the material is
      collected in isolation, thus preventing extensive taxonomic listings. Conducting
      inventories of terrestrial biodiversity in a specific area is an arduous task,
      with many obstacles: mainly the lack of data on taxonomic and geographical
      distribution necessary to study them. The aim of this work is to present new
      contributions to the geographical distribution of Heteroptera in the Pampean,
      Espinal and Monte phytogeographic provinces, in the central region of Argentina,
      Southern Cone. Ten samples were taken, using the following methods, beating
      sheet, light trap and G-Vac (garden-vacuum). Each point within the site was
      sampled by each type of trap for one minute, leading to a total of 10 minutes per
      capture method in each site, except the light tramp. Twenty-two species are
      recorded for the first time in the central region of Argentina, Southern Cone.

PMID- 27701243
TI  - Revision of the South American genus Xiphiola Bolivar, 1896 (Orthoptera:
      Acrididae: Ommatolampidinae: Abracrini).
AB  - The Neotropical genus Xiphiola Bolivar, 1896 is revised. It includes two valid
      species: Xiphiola borellii Giglio-Tos, 1900 and Xiphiola cyanoptera (Gerstaecker,
      1889). The genus and the species are redescribed and diagnostic characters are
      provided along with illustrations of each species. A lectotype and paralectoype
      for X. cyanoptera are here designated. We also include new morphological
      characters from male and female genitalia, and external characters that have not
      been employed until now. We present the distribution map based on material
      examined, as well as a key to species.

PMID- 27701244
TI  - A new species of Foleyellides (Nematoda: Onchocercidae) parasite of Lithobates
      spp. (Amphibia: Ranidae) from Mexico with a key for the species of the genus.
AB  - Thirty-six Foleyellides mayenae n. sp. were recovered from the body cavity of
      Lithobates psilonota (Webb, 2001) and L. pustulosus (Boulenger, 1883) (Ranidae)
      from Jalisco and Nayarit, respectively. Foleyellides mayenae is the eleventh
      species described for the genus and the third for Mexican amphibians; it differs
      from the other species of the genus by the following combined characters: five
      pairs of caudal papillae, 1 pre-anal, 1 adanal and 3 post-cloacal, and the
      absence of a preanal plaque.

PMID- 27701245
TI  - Lathrolestes Forster, 1869 (Hymenoptera, Ichneumonidae) from Brazil, with
      description of two new species and a key to the Neotropical species.
AB  - The taxonomic knowledge about Brazilian Ichneumonidae species is still incipient,
      especially for groups poorly represented in the Neotropics, like Ctenopelmatinae.
      The genus Lathrolestes Forster, 1869, mainly Holarctic, is here recorded for the
      first time to Brazil, with description of L. piranga Lima & Kumagai sp. n. and L.
      pitunauassu Lima & Kumagai sp. n. Additionally, a key to the Neotropical species
      is provided.

PMID- 27701246
TI  - CLAIRE E. GOODWIN, JADE BERMAN, DORTE JANUSSEN, CHRISTIAN GOCKE & KATHARINE R.
      HENDRY (2016) Hexactinellida (Porifera) from the Drake Passage (Southern Ocean)
      with a description of three new species. Zootaxa, 4126 (2): 207-220.

PMID- 27701247
TI  - Taxonomic studies on potter wasps (Hymenoptera: Vespidae: Eumeninae) of south
      India.
AB  - The family Vespidae is represented in India by four subfamilies: Vespinae,
      Polistinae, Stenogastrinae, and Eumeninae. The subfamily Eumeninae is the most
      species rich among the Vespidae. The potter wasps of south India are reviewed for
      the first time to comprise 31 valid genera. The genera Discoelius Latreille,
      1809, Coeleumenes van der Vecht, 1963, Euodynerus Dalla torre, 1904, and
      Pseudonortonia Giordani Soika, 1936 are newly reported from south India.
      Diagnoses and a key to south Indian eumenine genera are given. A total of 72
      species and subspecies are listed, 15 of them are newly reported from Karnataka
      and two species from Kerala.

PMID- 27701248
TI  - Reconsideration of the genera Merogomphus Martin, 1904, and Anisogomphus Selys,
      1857, including erection of a new genus, with a new species and discussion of
      additional specimens from Cambodia.
AB  - In the current sense, Merogomphus Martin, 1904, is an artificial genus. It
      includes two unrelated groups of species: those with lyrate cerci with or without
      an outer spine and those with simple cerci, plus two species with large and broad
      epiproct branches placed in Merogomphus obviously in error. At the same time a
      number of species similar and obviously related to the former group were
      described from China in the genus Anisogomphus Selys, 1857. To resolve this
      taxonomic tangle, the genus Merogomphus is restricted to include only species
      with lyrate cerci: M pavici (Martin, 1904) (the type species), M. longistigmus
      (Fraser, 1922), M. vandykei (Needham, 1930), M. femoralis (Laidlaw, 1931), M.
      vespertinus (Chao, 1999) and M. torpens (Needham, 1930). A new genus Euthygomphus
      (type species: Platygomphus martini Fraser, 1922) is erected to contain species
      with simple cerci and moderately divergent epiproct branches, formerly attributed
      to either Merogomphus or Anisogomphus: Euthygomphus parvus (Kruger, 1899) comb.
      nov., E. martini (Fraser, 1922) comb. nov., E. koxingai Chao, 1954 comb. nov., E.
      chaoi Liu 1991 comb. nov., E. jinggangshanus Liu, 1991 comb. nov., E. yunnanensis
      Zhou et Wu, 1992 comb. nov. Euthygomphus schorri  Kosterin, 2016, sp. nov. is
      described (type locality: Cambodia, Mondulkiri Province, 3.5-3.8 km ESE of Sen
      Monorom, holotype in RMNH), A new synonymy Merogomphus chaoi Yang & Davies, 1993
      = Anisogomphus pinratani Hamalainen, 1991, and a new combination Anisogomphus
      tamdaoensis (Karube, 2001) comb. nov. are proposed [corrected]. The published
      records of 'Merogomphus parvus' from Laos, Thailand, Vietnam, Cambodia and
      Vietnam are reidentified as E. yunnanensis, and new records and illustrations of
      this species from Cambodia are provided.

PMID- 27701249
TI  - New species and records of Galumnidae (Acari, Oribatida) from the Philippines.
AB  - We collected 19 species in eight genera of poronotic oribatid mites of the family
      Galumnidae from the Philippines. Five species, Galumna (Cosmogalumna) areticulata
      Ermilov, Sandmann, Klarner, Widyastuti & Scheu, 2015, G. (Neogalumna) tolstikovi
      Ermiov & Anichkin, 2014, Pergalumna (Pergalumna) crassipora Mahunka, 1995, P.
      (Pergalumna) margaritata Mahunka, 1989 and Trichogalumna nipponica (Aoki, 1966),
      the subgenus Galumna (Neogalumna) and the genus Trichogalumna are recorded for
      the first time in the fauna of this country. Three new species of the genera
      Pergalumna, Setogalumna and Trichogalumna are described. Pergalumna (Pergalumna)
      capualensis sp. nov. differs from P. (Pergalumna) bimaculata Hammer, 1973 and P.
      (Pergalumna) remota (Hammer, 1968) by the larger body length and the presence of
      strong teeth on prodorsum. Setogalumna minisetosa sp. nov. differs from S.
      luzonica Ermilov & Corpuz-Raros, 2015 by the smaller body size, the presence of
      minute interlamellar and notogastral setae, median pore and elongated notogastral
      porose areas A3, and the absence of notogastral porose areas A2. Trichogalumna
      interlamellaris sp. nov. differs from T. seminuda Balogh, 1960 by the larger body
      size, the presence of anterior notogastral margin and small bothridial heads, the
      absence of notogastral porose areas A2, and the localization of adanal setae
      ad<sub>3</sub>. Supplementary description of Pergalumna (Pergalumna) crassipora
      Mahunka, 1995 is presented.

PMID- 27701250
TI  - Review of the leafhopper tribe Stenometopiini (Hemiptera: Cicadellidae:
      Deltocephalinae) from China with description of four new species.
AB  - The leafhopper tribe Stenometopiini is revised from China. Two genera are
      included: Hodoedocus Jacobi with two species and Stirellus Osborn & Ball with
      thirteen species of which four are new: S. daii sp. nov., S. multipunctatus sp.
      nov., S. neospeciosus sp. nov., and S. translucidus sp. nov. S. yeongnamensis
      (Kwon & Lee) is newly recorded for China. Five new synonyms are proposed:
      Viridomarus brevialatus Xing et al. and Viridomarus laticellus Xing et al. as
      junior synonyms of S. capitatus (Distant); Aconura bipunctella Matsumura and
      Paivanana centristriata Dai & Li as junior synonyms of S. indrus (Distant);
      Aconura rubrofasciata Matsumura as junior synonym of S. rubrolineatus (Distant).
      Two new combinations are erected and one combination is reinstated (see
      checklist). Species are described and illustrated together with keys provided for
      their separation. Lectotypes are designated for Typhlocyba indra Distant and Arya
      rubrolineata Distant.

PMID- 27701251
TI  - A study on the genus Stenus Latreille from Tianmushan Mountain Chain of East
      China (Coleoptera, Staphylinidae).
AB  - The species of the genus Stenus Latreille from Tianmushan Mountain Chain, North
      Zhejiang, East China, are reviewed and three new species are described: S.
      tianmushanus sp. n., S. tonghanggangus sp. n., and S. pseudomicuba sp. n.
      Diagnostic characters of the new species are illustrated and a key to species of
      the area is provided.

PMID- 27701252
TI  - A new species of treefrog (Litoria) from Cape York Peninsula, Australia.
AB  - We describe a new species of treefrog from northern Australia. Litoria bella sp.
      nov. is morphologically and genetically most similar to frogs in the L.
      gracilenta and L. chloris groups but is distinguished from all members in these
      groups by a combination of a moderately large male body size (34.5-41.8 mm SVL),
      near-immaculate green dorsum, orange venter, bright orange digits and webbing,
      bluish purple lateral surfaces of the thighs, no pale canthal stripe, white
      bones, and a highly-pulsed, single-note, male advertisement call with a pulse
      rate of 56-64 pulses/s and dominant frequency of 2.6-2.8 kHz. Litoria bella sp.
      nov. has a patchy distribution across the Cape York Peninsula, inhabiting
      rainforest and monsoon vine thicket in close association with watercourses. The
      new species' affinities lie with L. auae from southern New Guinea rather than
      with L. gracilenta from eastern Australia. Molecular data suggest that the L.
      gracilenta group should be expanded to include L. chloris and L. xanthomera, two
      moderately large green treefrogs from eastern Australia.

PMID- 27701253
TI  - The genus Prothrombosternus (Coleoptera: Curculionidae: Molytinae) rediscovered:
      a male from Rubeho Mountains, Tanzania.
AB  - A male specimen of the monotypic weevil genus, Prothrombosternus Voss, 1965, so
      far known on the basis of only five syntypes from Mt. Meru and Mt. Hanang,
      Tanzania, is reported from the Rubeho Mountains, Tanzania. The lectotype of
      Prothrombosternus tarsalis Voss, 1965 is designated using a male from Mt. Meru.
      The Rubeho specimen shares the same external and genital morphological characters
      with the lectotype (both extensively illustrated) and, therefore, both are
      considered conspecific. The DNA barcode of the Rubeho specimen is publicly
      available at dx.doi.org/10.5883/DS-PROTHRO. All six known specimens of
      Prothrombosternus are flightless and were found by sifting leaf litter at
      elevations between 1833-2500 m in wet Afromontane forests. The genus is,
      therefore, thought to be restricted to this highly fragmented habitat threatened
      by human encroachment. Presence of the genus on both geologically old (Rubeho
      Mountains; >10Ma) and young (Mt. Meru and Mt. Hanang volcanoes, <2Ma) forested
      highlands suggests presently unknown means of dispersal. The phylogenetic
      position of the genus is unknown and its taxonomic placement in Cycloterini
      cannot be presently tested.

PMID- 27701254
TI  - Notes on west Palaearctic species of the genus Trigonurus Mulsant, 1847
      (Coleoptera: Staphylinidae: Trigonurinae).
AB  - The subfamily Trigonurinae Reiche, 1866 is a monogeneric subfamily of the large
      family Staphylinidae with an Holarctic distribution. The genus was the subject of
      a revision (Blackwelder, 1941). Seven species are known from northern America
      (Blackwelder, 1941; Herman, 2001), two species from the western Palaearctic and
      two, recently described species from China (Schulke & Smetana, 2015; Kishimoto,
      2000; Schulke, 2006).

PMID- 27701255
TI  - A new species of the genus Apollophanes O. Pickard-Cambridge, 1898 (Araneae:
      Philodromidae) with the first record to the Atlantic rainforest.
AB  - Apollophanes has a wide distribution, with some species in Asia and most of the
      species recorded from North and Central America (World Spider Catalog 2016). New
      species described from the Galapagos Islands by Baert (2013) have extended the
      genus range to South America. According to Dondale and Redner (1975) and Dondale
      and Redner (1978), the species of Apollophanes have a moderately low prosoma,
      usually of yellow to orange-brown color and with black or brown spots on the
      lateral margins. The posterior eyes distances are equally spaced and the legs are
      long, slender and speckled with dark spots, with leg I usually being longer than
      IV (characteristic observed only in the male exemplar of the new species). The
      opisthosoma has a conspicuous heart mark, dark longitudinal spots on the lateral
      margins and a pale ventral region with purple spots. According to Dondale and
      Redner (1975) and Logunov (1996), Apollophanes shares some features with species
      of Cleocnemis, Thanatus and Tibellus, e.g. the shape and coloration patterns of
      the dorsal shield of the prosoma, as well as the slender legs with dark spots.
      Apollophanes can be distinguished from Cleocnemis by the presence of two tibial
      apophyses (ventral and retrolateral) and by the size of the copulatory ducts
      openings that are long slits that reach the posterior margin of epigastric furrow
      in Apollophanes, while in Cleocnemis the openings are shorter and situated in
      central region of the median septum (Dondale & Redner 1975). Apollophanes differs
      from Thanatus by the presence of macrosetae on the prolateral region of the
      metatarsus, and differs from Tibellus by the size of leg IV, that is longer than
      leg I (Dondale & Redner 1975).

PMID- 27701256
TI  - One new species of the subgenus Xizicus (Zangxizicus) (Orthoptera: Tettigoniidae:
      Meconematinae) from China.
AB  - The paper reports one new species of the tribe Meconematini, Xizicus
      (Zangxizicus), curvus Chang & Shi sp. nov., and supplies the character
      photographs of the new species and Xizicus(Zangxizicus) tibeticus Wang, Jing, Liu
      & Li, 2014.

PMID- 27701257
TI  - Confirmation of the occurrence of the sandbar shark Carcharhinus plumbeus (Nardo,
      1827) at Norfolk Island, Tasman Sea.
AB  - The occurrence of the sandbar shark Carcharhinus plumbeus at Norfolk Island is
      confirmed. Carcharhinus plumbeus occurs over the mid to outer insular shelf from
      38 m to at least 53 m depth, and appears to be at least as abundant as C.
      galapagensis in this habitat. No C. plumbeus were caught from shore despite most
      fishing effort being land-based. The presence of young-of-the-year confirms C.
      plumbeus breeds on the Norfolk Island shelf. Size at birth and the timing of
      parturition appear similar to that reported for eastern Australia.

PMID- 27701258
TI  - The identity of Calliphora bezzii Zumpt, 1956 (Diptera, Calliphoridae).
AB  - The holotype male of a nominal species described from Italy, Calliphora bezzii
      Zumpt, 1956, including a microscope slide of its terminalia, was examined. The
      holotype is shown to belong to the Nearctic taxon Calliphora latifrons Hough,
      1899. Thus, Calliphora bezzii is a junior synonym of C. latifrons, syn. nov.

PMID- 27701259
TI  - New records of Panchaetothripinae from Japan (Thysanoptera, Thripidae).
AB  - Until now, 16 species of Panchaetothripinae in 11genera have been recorded from
      Japan (Kudo 1992a,b). Recently, however, three further species were found, in the
      genera Phibalothrips and Caliothrips, and one purpose of this report is to record
      these two genera from Japan for the first time. The four known species of
      Phibalothrips occur mainly in the Old World tropics, and are associated with
      grasses (Mound 2011), whereas the 22 known species of Caliothrips are found in
      the tropics and subtropics worldwide and feed on a range of different plants
      including grasses. In this article, P. rugosus, C. punctipennis and C. tongi are
      newly recorded from Japan, and the male of P. rugosus and second instar larva of
      C. tongi are described for the first time. Moreover, an identification key to the
      known species of Phibalothrips is provided. Larval chaetotaxy is based on Heming
      (1991) and Vierbergen et al. (2010). The specimens studied are deposited in
      Yokohama Plant Protection Station, Naha Plant Protection Station and the authors'
      collection.

PMID- 27701260
TI  - Further studies on south eastern Asian Luciolinae: 1. Sclerotia Ballantyne, <br
      />a new genus of fireflies with back swimming larvae 2. Triangulara Pimpasalee, a
      new genus from Thailand (Coleoptera: Lampyridae).
AB  - Sclerotia Ballantyne gen. nov. is established for seven species. Sclerotia
      aquatilis (Thancharoen, 2007), Scl. brahmina (Bourgeois, 1890), Scl. carinata
      (Gorham, 1880), Scl. flavida (Hope, 1845), Scl. seriata (Olivier, 1891), and Scl.
      substriata (Gorham, 1880) are transferred from Luciola Laporte. Sclerotia fui sp.
      nov. from China is described as new. Luciola cingulata Olivier, 1885 is
      synonymised with Luciola substriata Gorham. Luciola formosana Pic, 1916 is
      removed from synonymy with Luciola substriata and newly synonymised with Luciola
      flavida (Hope). Males are characterised by linear elytral punctation, a set of
      three sclerites surrounding the aedeagal sheath and a light organ in ventrite 7
      with emarginated anterior margin. Associated females lack bursa plates. Larvae
      associated for three species are back swimmers, having heavily sclerotised
      exoskeleton and a metapneustic respiratory system. Males and associated females
      are keyed. Analysis of molecular evidence for Chinese populations of three
      species indicates monophyly of Sclerotia Ballantyne gen. nov. and distinct
      separation from other genera.Triangulara Pimpasalee gen. nov. is described from
      Tri. frontoflava Pimpasalee gen. et sp. nov. from Thailand. It is superficially
      similar to Sclerotia gen. nov. but larger, and specimens in collections appear to
      have been confused with the similarly coloured Scl. substriata (Gorham) comb.
      nov. Males differ in having an elongate triangular light organ in ventrite 7 and
      are without sclerites around the aedeagal sheath. Larvae are not reliably
      associated but may be aquatic.

PMID- 27701261
TI  - The genus Zelurus Hahn, 1826, in Brazilian caves: description of new species and
      comments on the potential distribution of the genus in South America.
AB  - A survey on species of the genus Zelurus Hahn, 1826 (Reduviidae) occurring in
      Brazilian caves is provided. Zelurus tambejua sp. n. and Zelurus gerevatinga sp.
      n. collected from caves in Brazil are described. Comments about the current and
      potential distribution of the genus as a whole and of species of Zelurus found in
      caves for South America are also provided.

PMID- 27701262
TI  - Taxonomic revision of the Dasypus kappleri complex, with revalidations of Dasypus
      pastasae (Thomas, 1901) and Dasypus beniensis Lonnberg, 1942 (Cingulata,
      Dasypodidae).
AB  - Dasypus kappleri is the largest species of the genus Dasypus and is restricted to
      the Amazonian rainforest biome. Over the last century, related taxa have been
      described and synonymized without comprehensive analyses, and the current
      classification involving two subspecies, Dasypus k. kappleri and Dasypus k.
      pastasae, has never been revised. The aim of this work is to clarify the taxonomy
      of Dasypus kappleri through integrative morphological and morphometric analyses.
      We examined 70 specimens housed in scientific collections as well as photographs
      of the type specimens of five nominal taxa. Three methodologies (discrete
      characters, linear and geometric morphometrics) were employed. All results
      converged on the recognition of three allopatric groups, each with diagnostic
      qualitative and quantitative traits, that we recognize as full species: Dasypus
      kappleri Krauss, 1862, occurs in the Guiana shield; Dasypus pastasae (Thomas,
      1901) is distributed from the eastern Andes of Peru, Ecuador, Colombia, and
      Venezuela south of the Orinoco River into the western Brazilian Amazon; and
      Dasypus beniensis Lonnberg, 1942, occurs in the lowlands of Amazonian Brazil and
      Bolivia to the south of the Madre de Dios, Madeira, and lower Amazon rivers. This
      revision raises to nine the number of living species of Dasypus.

PMID- 27701263
TI  - Two new species of brackish-water Macrostomum (Platyhelminthes, Macrostomida)
      from southern China.
AB  - Two new species of brackish-water Macrostomum (M. zhujiangensis n. sp. and M.
      baoanensis n. sp.) were described based on samples collected from the littoral
      zone of the Zhujiang Estuary. These are the first records of brackish-water
      Macrostomum from southern China. Macrostomum zhujiangensis n. sp. and M.
      baoanensis n. sp. differ from other similar species in the length and morphology
      of the penis stylet.  The penis stylet of M. zhujiangensis n. sp. is C-shaped and
      its distal opening has a beveled edge. The penis stylet of M. baoanensis n. sp.
      is J-shaped and the distal region is thicker than other parts of the penis
      stylet. Molecular phylogenetic analysis supports the establishment of the new
      species.

PMID- 27701264
TI  - The Pinnotheridae of the northeastern Pacific (Alaska to Mexico): zoogeographical
      remarks and new bivalve hosts (Crustacea, Brachyura, Pinnotheridae).
AB  - New bivalve host records for four pinnotherid crabs of the Mexican Pacific are
      reported: Fabia subquadrata Dana, 1851, in Modiolus capax (Conrad, 1837);
      Opisthopus transversus Rathbun, 1893, in Tivela stultorum (Mawe, 1823);
      Pinnaxodes gigas (Green, 1992), in Pinna rugosa (Sowerby, 1835), and Panopea
      generosa Gould, 1850; and Tumidotheres margarita (Smith, 1870), in Nodipecten
      subnodosus (Sowerby, 1835). The southernmost distribution of F. subquadrata is
      extended to about 600 km along the west coast of the Baja California Peninsula;
      the distribution of P. gigas is extended outside the Gulf of California more than
      1000 km north to San Quintin, on the west coast of Baja California; and the range
      of T. margarita is restricted on the west coast of Baja California to Scammon's
      Lagoon, Baja California Sur and Playa Kino Viejo, Sonora in the central region of
      the Gulf of California, Mexico to Panama. Based on the new material, new
      information on taxonomy, ecology, and life history is provided for each of these
      species. Pinnotheres nudus Holmes, 1895 is restored as a valid species and is
      removed from its synonymy with O. transversus. An updated checklist with remarks
      on zoogeography for the 60 pinnotherid species, included in 23 genera, of the
      northeastern Pacific region (Alaska to the Mexican tropical Pacific) is given.

PMID- 27701265
TI  - Diagnosis of Calagasma Bergroth and Epipedus Spinola with description of
      Calagasma eclipsa sp. nov. and Epipedus rolstoni sp. nov. (Hemiptera:
      Heteroptera: Pentatomidae: Pentatominae: Carpocorini).
AB  - The genus Calagasma Bergroth synonymized with the genus Epipedus Spinola by
      Rolston (1987) is reinstated. The diagnostic characters of the genus Calagasma
      are redefined, pictures of the Calagasma margarita syntype and recently collected
      specimens from French Guiana, including males hitherto unknown are presented.
      Calagasma eclipsa, a new species from French Guiana is described. Epipedus is
      redescribed and a new species Epipedus rolstoni is described.

PMID- 27701266
TI  - A new species of the Cyrtodactylus (Geckoella) collegalensis (Beddome, 1870)
      complex (Squamata: Gekkonidae) from Western India.
AB  - A new species of Cyrtodactylus (Geckoella) from the C. collegalensis complex is
      described based on a series of specimens from western and central India.
      Morphological and molecular data support the distinctiveness of the new form,
      which can be diagnosed from other Cyrtodactylus (including other Geckoella)
      species by its small body size (snout to vent length to 56 mm), the absence of
      precloacal and femoral pores, no enlarged preanal or femoral scales, and a dorsal
      scalation consisting wholly of small, granular scales. The new species is most
      closely related to C. collegalensis, C. speciosus and C. yakhuna, from which it
      differs by the presence of a patch of enlarged roughly hexagonal scales on the
      canthus rostralis and beneath the angle of jaw, its relatively long limbs and
      narrow body, and a dorsal colour pattern of 4-6 pairs of dark spots.

PMID- 27701267
TI  - The distribution of the Bururi Long-fingered Frog (Cardioglossa cyaneospila,
      family Arthroleptidae), a poorly known Albertine Rift endemic.
AB  - The species diversity of the frog genus Cardioglossa (family Arthroleptidae) is
      concentrated in the Lower Guinean Forest Zone of Central Africa with most of the
      19 species occurring in Cameroon and neighboring countries (Amiet 1972a,b;
      Blackburn 2008; Hirschfeld et al. 2015). These small leaf-litter frogs are
      typically found in primary or secondary forest, have shrill whistling calls, are
      characterized by a variety of color patterns, and lay terrestrial eggs that hatch
      and develop into elongate, stream-adapted tadpoles (Amiet 1972a,b, 1973; Rodel et
      al. 2001; Hirschfeld et al. 2012). One of the most poorly known species-the
      Bururi Long-fingered Frog Cardioglossa cyaneospila Laurent, 1950-is also among
      the most geographically peripheral to the rest of the species diversity. To date,
      it is known only from two locations in Burundi and four in eastern Democratic
      Republic of Congo, regions in which armed conflicts have long hampered scientific
      research. In this short contribution, we (1) document both new and long
      unpublished records of C. cyaneospila, associate these with known museum records,
      and extend its geographic range, (2) highlight fruitful areas for future field
      surveys based on predicting an environmental envelope for this species, and (3)
      summarize what little is known of its natural history.

PMID- 27701268
TI  - The Afrotropical genus Rhinolaetia Schouteden, 1965 and its systematic position
      within Scutelleridae (Hemiptera: Heteroptera).
AB  - The monotypic Afrotropical genus Rhinolaetia Schouteden, 1865 (Hemiptera:
      Heteroptera: Scutelleridae) is redescribed. The head, wings, female genitalia and
      habitus of Rhinolaetia overlaeti Schouteden, 1965 are illustrated. Morphological
      features of Rhinolaetia and selected representatives of six scutellerid
      subfamilies are listed and compared. The systematic position of this genus is
      briefly discussed. Close affinity of Rhinolaetia overlaeti with representatives
      of subfamilies Odontotarsinae and Odontoscelinae is observed.

PMID- 27701269
TI  - Hybothoracaphis, a new genus of Nipponaphidini (Hemiptera, Aphididae,
      Hormaphidinae) from China and its phylogenetic placement based on multiple genes.
AB  - Hybothoracaphis gen. nov. with one new species Hybothoracaphis laevigata sp. nov.
      on Quercus aquifolioides from Tibet, China is described and illustrated in the
      aphid tribe Nipponaphidini. The phylogenetic position of the new genus within
      Nipponaphidini is investigated using multiple genes, and a key to Hybothoracaphis
      and allied genera is provided.

PMID- 27701270
TI  - A new species of seahorse (Teleostei: Syngnathidae) from the South China Sea.
AB  - A new species of seahorse, Hippocampus casscsio sp. nov. was collected over
      shallow seagrass beds in Beibu Bay, China. This species is diagnosed from all
      other seahorse species by morphological characters, including the lower number of
      tail rings (35); 15 pectoral-fin rays; 16 dorsal-fin rays; a rounded nuchal plate
      without a raised coronet; a snout length 30% head length; two cheek spines and a
      dark brown coloration. In addition, molecular analysis showed all individuals of
      the new species clustering together suggesting a monophyletic lineage. This
      combined analysis supports the distinctness of H. casscsio sp. nov. as a new
      species, which is described herein.

PMID- 27701271
TI  - First records of the cremastocheiline genus Clinterocera Motschulsky, 1858 from
      the Indonesian island of Sulawesi, with description of a new species (Coleoptera:
      Scarabaeidae: Cetoniinae).
AB  - A new species of the myrmecophilous Asian genus Clinterocera Motschulsky, 1858
      (Coleoptera: Scarabaeidae: Cetoniinae: Cremastocheilini) is recorded from three
      localities on different parts of Sulawesi island (Indonesia). These are the first
      published records of the genus from the island. The taxonomic position and
      ecology of Clinterocera are briefly discussed. The male holotype of Clinterocera
      heinrichi new species comes from Central Sulawesi while a second male specimen
      from North Sulawesi male seems different enough to be placed in another species
      group taxon, but more material needs to be examined first.

PMID- 27701272
TI  - Thirteen new species of the spider genus Pholcus Walckenaer, 1805 (Araneae:
      Pholcidae) from China.
AB  - Thirteen new species from four species groups of the genus Pholcus Walckenaer,
      1805 are described from China: Pholcus yanjinensis sp. nov. (male & female,
      Yunnan) from the P. bidentatus species group; P. jingyangensis sp. nov. (male &
      female, Shaanxi), P. langensis sp. nov. (male & female, Henan) and P. longus sp.
      nov. (male & female, Beijing) from the P. crypticolens species group; P.
      huoxiaerensis sp. nov. (male, Xinjiang) from the P. ponticus species group; P.
      difengensis sp. nov. (male, Chongqing), P. gonggarensis sp. nov. (male & female,
      Tibet), P. hamaensis sp. nov. (male & female, Guizhou), P. lingguanensis sp. nov.
      (male & female, Henan), P. qingyunensis sp. nov. (male & female, Jiangxi), P.
      tangyuensis sp. nov. (male & female, Shaanxi), P. tianmuensis sp. nov. (male &
      female, Zhejiang) and P. zhongdongensis sp. nov. (male & female, Guangxi) from
      the P. yichengicus species group.

PMID- 27701273
TI  - Five new records and an annotated checklist of the leeches (Annelida: Hirudinida)
      of Iran.
AB  - The present checklist contains 22 species belonging to 14 genera of six families
      of leeches known to date from Iran. Five species including Dina punctata punctata
      Johannson, 1927, Erpobdella monostriata (Lindenfeld & Pietruszynski, 1890), E.
      vilnensis (Liskiewicz, 1925), Trocheta haskonis Grosser, 2000 and Glossiphonia
      concolor (Apathty, 1888) are new records for the country.

PMID- 27701275
TI  - Four colorful new species of dragon millipedes, genus Desmoxytes Chamberlin,
      1923, from northern Thailand (Diplopoda: Polydesmida: Paradoxosomatidae).
AB  - Four new dragon millipede species of the genus Desmoxytes from northern Thailand
      are described and illustrated: D. des sp. n. from Chiang Mai Province, D.
      breviverpa sp. n. from Phrae Province, D. takensis sp. n. from Tak Province and
      D. pinnasquali sp. n. from Phitsanulok Province. The new species were compared
      with type specimens of closely related species and were all found to exhibit
      explicit morphological differences from these. They can be distinguished from
      other members of Desmoxytes by the shape of the gonopods, the sternal process
      between male coxae 4, the pattern of spines or tubercles on the metaterga, and
      the shape of the paraterga. The coloration of all new species is clearly
      aposematic: ranging from purple-pink to red. The new species are discussed in
      relation to their congeners, and a distribution map is provided.

PMID- 27701274
TI  - Prosorhynchus Odhner, 1905 (Digenea: Bucephalidae) from the orange-spotted
      grouper Epinephelus coioides (Hamilton, 1822) (Epinephelidae), including
      Prosorhynchus tonkinensis n. sp., from the Gulf of Tonkin, Vietnam.
AB  - A total of 169 specimens of the orange-spotted grouper Epinephelus coioides
      (Hamilton) were collected from fishermen and marine fish farms in the Gulf of
      Tonkin, Vietnam. Five different species of Prosorhynchus Odhner, 1905 were
      recorded, including P. tonkinensis n. sp. The new species differs from all other
      Prosorhynchus species in the presence of an indented posterior extremity. It can
      be distinguished from the most closely related P. atlanticus Manter, 1940 and P.
      crucibulum Rudolphi, 1819 by the extension of the uterus always to the level of
      the ovary, the width and premouth distance in the former, and the arched
      vitellarium and smaller egg size in the latter, and a different host and
      geographical region. Prosorhynchus sp. A (not fully identified in this study) has
      been earlier reported from E. coioides from New Caledonia (see Prosorhynchus sp.
      B of Bray and Justine, 2013), P. luzonicus Velasquez, 1959 is reported throughout
      South-East Asia, and Prosorhynchus sp. B (no further identification possible
      based on a single specimen in this study) and P. maternus Bray & Justine, 2006
      are reported for the first time from Vietnam. The present study demonstrates a
      close relationship of the Prosorhynchus species composition in Vietnam with the
      Indo-Australian region, warranting further comparative studies among the
      different epinephelids.

PMID- 27701276
TI  - Two new species of Caenis Stephens, 1835 (Ephemeroptera: Caenidae) from South
      America.
AB  - Caenis Stephens, 1835 is a relatively diverse South American genus of Caenidae
      (Ephemeroptera), with 22 recorded species, but much of its diversity remains
      poorly explored in this region. In the present study, two new species of Caenis
      with apically pointed forceps are described: Caenis amacayacu sp. nov., based on
      male adults from Colombia; and C. elidioi sp. nov, based on all life stages from
      several localities in Brazil.

PMID- 27701277
TI  - The first Turcolana Argano & Pesce, 1980 (Isopoda: Cirolanidae) from the Greek
      mainland.
AB  - Turcolana Argano & Pesce, 1980 is the isopod genus occurring in freshwater and
      brackish groundwater environments around the eastern Mediterranean. In this
      study, a revised diagnosis of the genus, an updated map of species distribution
      and a key to species are presented. The first cave dwelling species is described
      from the Melissotrypa Cave in central Greece, a highly troglomorphic Turcolana
      lepturoides sp. nov. Its principal distinguishing characters are elongated
      appendages: styliform uropods (twice as long as pleotelson), antennae (half as
      long as body) and pereopods (e.g. pereopod 7 45% as long as body). Mitochondrial
      DNA sequences (16S rRNA, 12S rRNA) of the new species are provided.

PMID- 27701279
TI  - Review of the genus Defilippia Lioy (Bombyliidae, Diptera) from Egypt, with
      description of a new species, new combinations, and a neotype designation for D.
      pharaonis (Paramonov, 1928).
AB  - In the present study, five Defilippia species are shown to be represented in
      Egypt. Two species, D. efflatouni (Bezzi) and D. minos (Meigen), were already
      included in Defilippia; two species, D. decrepita (Wiedemann), comb. nov., and D.
      pharaonis (Paramonov), comb. nov., are newly combined to Defilippia; and a new
      species, D. elbayensis, sp. nov., is described herein. Homeotypes of Exoprosopa
      flava Paramonov, 1928 and Defilippia decrepita (Wiedemann, 1828), comb. nov. have
      been examined and it was found that the two species are not synonymous and
      Exoprosopa flava Paramonov, 1928,  stat. rev. is rather a distinct valid species
      in its original genus Exoprosopa. A neotype for D. pharaonis (Paramonov, 1928) is
      designated.

PMID- 27701278
TI  - Cathorops festae (Boulenger 1898) (Siluriformes; Ariidae), a valid species from
      Ecuador and Peru.
AB  - Over the past decade, the Sea Catfish (Ariidae) genus Cathorops has been the
      focus of a major taxonomic review, which has resulted in the revalidation of five
      synonymized nominal species, and the recognition of seven new species. With 21
      valid species, Cathorops is currently the most species-rich genus of Ariidae in
      the New World. The principal lacuna in the taxonomic knowledge of genus species
      is the uncertain status of Arius festae Boulenger, 1898, described from Naranjal,
      in the Guayas River basin of Ecuador. In the present study Cathorops festae is
      redescribed as a valid species based on morphological and molecular data.

PMID- 27701280
TI  - Descriptions, transference and new records of Lamiinae from Central and South
      America (Coleoptera, Cerambycidae).
AB  - Two new species are described in Calliini: Callisema jirouxi sp. nov. from
      Ecuador and Colombicallia setosa sp. nov. from Costa Rica. Keys to species of
      Callisema and Colombicallia are provided. Psapharochrus alboguttatus (Melzer,
      1935) is transferred to Alphus White, 1855. New country, department and state
      records are provided in Lamiinae.

PMID- 27701281
TI  - The systematic position of Hypsugo macrotis (Chiroptera: Vespertilionidae) and a
      new record from Peninsular Malaysia.
AB  - The Southeast Asian species of Hypsugo are rare bats, except for H. cadornae and
      H. pulveratus, which are distributed throughout the Indomalayan region. Hypsugo
      macrotis is restricted to Peninsular Malaysia, Sumatra, Java and adjacent
      islands, and is known only from a handful of specimens. Here we report a new
      locality record of the species from Seremban, Peninsular Malaysia, which also
      represents the first known building-dweller colony of any Hypsugo from the
      region. We discuss the taxonomic status of two morphologically similar species,
      H. macrotis and H. vordermanni, and provide the first COI and cyt b gene
      sequences for H. macrotis and reconstruct the species' phylogenetic
      relationships.

PMID- 27701282
TI  - Two new species of gill parasites assigned to Protoancylodiscoides (Monogenea,
      Ancyrocephalidae) from Chrysichthys spp. (Siluriformes, Claroteidae) in River
      Sanaga (Cameroon).
AB  - Host specimens were sampled in the middle course of the River Sanaga (Cameroon)
      from January to October 2014. Two new species, Protoancylodiscoides auratum n.
      sp. from Chrysichthys auratus and Protoancylodiscoides combesi n. sp. from C.
      auratus, Chrysichthys nigrodigitatus and Chrysichthys longidorsalis, are herein
      described. These new helminths differ from the congeneric species by the size of
      the haptoral sclerites, the male copulatory organ length, the diameter and
      morphology of the vagina. At this stage, the present study suggests that
      Protoancylodiscoides auratum is oioxenous, while P. combesi is stenoxenous. The
      two new Protoancylodiscoides species bring to three the number of those
      parasitizing C. auratus, and to four the number of those described from
      Chrysichthys spp.

PMID- 27701283
TI  - A remarkable new species of winter stonefly (Plecoptera: Capniidae) from
      Southeastern China.
AB  - A new species of the genus Capnia s.l., C. zijinshana Du & Chen, sp. nov. is
      described and illustrated from Jiangsu Province, of southeastern China. The new
      species is distinguished from other known Chinese capniid species by the unique
      thoracic sclerites and genitalic characters.

PMID- 27701284
TI  - A new species of the Aphaenogaster cecconii group (Hymenoptera: Formicidae) from
      Rhodes.
AB  - Aphaenogaster charesi, a new species in the A. cecconii group, is described from
      two localities on the island of Rhodes. The recent revision of the group by
      Borowiec and Salata is updated with (1) a modified key to include this new
      species, (2) new locality and habitat data for A. jolantae Borowiec & Salata,
      2014, and (3) corrected measurements for A. olympica Borowiec & Salata, 2014.

PMID- 27701285
TI  - Species of braconid wasps described by Christian Godfried Nees ab Esenbeck in
      1811, 1812, 1816, 1818, 1834. A revisionary checklist (Hymenoptera, Braconidae).
AB  - In his five publications Nees (1811-1834) described 263 braconid species
      originating mainly from Germany and, less in number, from a further seven
      countries in Europe. The braconid species were assigned to 19 genera: twelve have
      been created by him and the rest (seven genera) by three other authors. The
      majority of the species (218) remained valid, the rest of the names (45) were
      placed in synonymy (by other authors). By his descriptions the species and genera
      are more or less recognizable, nevertheless their redescriptions are promoting
      their unambiguous recognition. In the first checklist provided, the genera and
      species are presented following Nees's original denominations and the current
      valid generic and species names are listed (denoted by an equals (=) sign). In
      the second checklist, the current valid generic and species names are compared
      with the original generic and species names. In the third checklist, the braconid
      species of 16 other authors included in Nees five publications are listed. New
      author's names for three species are provided: Doryctes leucogaster Ziegler, 1834
      (Bacon), Microgaster nigricans Gyllenhal, 1834 and Microplitis sordipes (Ziegler,
      1834) (Microgaster); the author of these three species was Nees. The Nees
      Collection (braconid and other material) was destroyed at the end of the Second
      World War.

PMID- 27701286
TI  - A systematic revision of the genus Gnophopsodos Wehrli, 1945, with description of
      two new species (Lepidoptera: Geometridae).
AB  - In a comprehensive morphological study besides results of DNA barcoding the genus
      Gnophopsodos Wehrli, 1945 is taxonomically revised. The taxon comprises nine
      species. Diagnostic characters are depicted and a key to the species based on the
      morphology of male genitalia is provided. Males and females (if available) of
      each species and their genitalia are illustrated. The distribution of all species
      is described and figured on maps. Gnophopsodos hilmari spec. nov. from Uzbekistan
      and Kyrgyzstan, Gnophopsodos sabine spec. nov. and Gnophopsodos ravistriolaria
      pantherinus subspec. nov., both from the Russian part of the Altai Mountains, are
      described as new. Gnophopsodos puengeleri (Bohatsch, 1910) stat. rev. is re
      established as a separate species. The following synonyms are recognized:
      Chelegnophos Wehrli, 1951 syn. nov. of Gnophopsodos Wehrli, 1945; Chelegnophos
      alaianus Viidalepp, 1988 syn. nov. of Gnophopsodos puengeleri (Bohatsch, 1910),
      Psodos altissimaria Oberthur, 1913 syn. nov. of Gnophopsodos gnophosaria
      (Oberthur, 1893), and Gnophos orbicularia Pungeler, 1904 syn. nov. of
      Gnophopsodos stemmataria (Eversmann, 1848) comb. nov. The latter is transferred
      from the genus Gnophos Treitschke, 1825 to the genus Gnophopsodos.

PMID- 27701287
TI  - Immature stages and larval chaetotaxy of Notofairchildia stenygros (Quate &
      Alexander) (Diptera: Psychodidae: Bruchomyiinae).
AB  - Some authors have hypothesized that Bruchomyiinae is "the most plesiomorphic
      subfamily of Psychodidae" and its members "are among the most primitive living
      Diptera". Although Bruchomyiinae is of no medical importance, it is of great
      evolutionary significance, having long been placed as the sister group of
      Phlebotominae. In general, species of this subfamily are rarely collected in
      their natural environment; therefore, adults and, even more so, the immature
      stages of these flies are poorly known. We describe the egg, larvae and pupae of
      Notofairchildia stenygros and provide nomenclatural notes on larval chaetotaxy
      based on analyses using scanning electron microscopy (SEM) and optic microscopy.
      The morphology of immature Nt. stenygros is compared with other Bruchomyiinae and
      Psychodidae species, especially with species of Phlebotominae that are
      superficially similar to Bruchomyiinae. Results of this study revealed striking
      morphological differences between the immature stages of Bruchomyiinae and
      Phlebotominae; the former are lacking abdominal pseudopods and microtrichia on
      the cephalic integument, both of which are present in the larvae of
      Phlebotominae. These morphological differences observed in the immature stages
      between members of the two subfamilies support the findings of recent molecular
      studies indicating that Bruchomyiinae and Phlebtominae are evolutionarily not
      closely related. Notofairchildia stenygros is now the fourth species of
      Bruchomyiinae for which the immature stages are described.

PMID- 27701288
TI  - A new species of salamander of the genus Hynobius (Amphibia, Caudata, Hynobiidae)
      from South Korea.
AB  - We describe a new species of lentic-breeding Hynobius salamander from the Naro
      Islands, near the village of Bongrae-myeon, Goheung-gun, Jeollanam-do, South
      Korea, on the basis of results of morphological, ecological and genetic analyses.
      Hynobius unisacculus sp. nov. is distinguished from its congeners by a
      combination of the following morphological attributes: (1) comparatively small
      size (adult SVL up to 61 mm; range 38.3-60.3 mm in males and 37.5-59.9 mm in
      females); (2) relatively slender short limbs; tips of fore- and hindlimbs
      adpressed on body never meeting, but separated by a large gap (gap of -3.0 to 
      1.5 costal folds in males and -3.5 to -1.5 in females); (3) comparatively short
      tail (TL/SVL ratio in adult males varying from 0.54-0.98, in adult females from
      0.55 to 0.89), tail flattened and with a low dorsal fin extending to the
      posterior one-third of tail length; (4) usually 11 (occasionally 12) costal
      grooves; (5) in adults, dark brown dorsum with indistinct bronze or dark copper
      spots, lighter greyish-white or pinkish belly; (6) well developed fifth toe; (7)
      comparatively shallow vomerine tooth series with 13-23 vomerine teeth; (8) small,
      pigmented ova, located in one, occasionally two, strings in a small, curved egg
      sac with folded envelope, lacking distinct mucous stalks or whiptail-like
      structures on both ends. The molecular differentiation among Korean Hynobius is
      high; Hynobius unisacculus sp. nov. is genetically highly divergent from the
      morphologically similar H. leechii, H. yangi and H. quelpaertensis: pairwise
      distances are 9.7%, 9.1% and 8.0% of sequence divergence at the COI mtDNA gene
      respectively, and 10.9%, 10.9% and 9.4% of sequence divergence at the cyt b mtDNA
      gene, respectively. At present, the new species is known from coastal areas and
      offshore islands in southeastern part of Jeollanam-do in South Korea. We suggest
      the species should be considered as Vulnerable (Vu2a) in accordance with IUCN's
      Red List categories. Our study supports the presence of undiagnosed taxonomic
      diversity among Korean Hynobius.

PMID- 27701289
TI  - The uncommon Neotropical genus Pazius Navas, 1913 (Mecoptera: Bittacidae): a
      comprehensive synthesis, with description of a new Brazilian species.
AB  - After a gap of more than twenty years, only recently the uncommon Neotropical
      genus Pazius Navas, 1913 has been focus of scientific researches, with the
      description of two new species from Colombia. Here all the knowledge about the
      genus is synthetized, with an identification key to all species, including
      comprehensive illustrations of male's terminalia and the description of Pazius
      angaibara sp. nov. from Northern Brazil. Also, a geographic records map of the
      genus is included.

PMID- 27701291
TI  - Re-definition and review of the Oriental genus Hexachaetus Chaudoir, 1871
      (Coleoptera: Carabidae: Orthogoniini).
AB  - The ground beetle genus Hexachaetus Chaudoir, 1871 is re-defined and reviewed.
      Bearing six setae on ligula is no more considered as a crucial characteristic for
      Hexachaetus. Members of Hexachaetus share the following combination of
      morphological features: body polish, smooth, and impunctate, ligula more or less
      dilated at apex, bearing 4, 6, or even 12 setae apically, prosternal process
      unbordered at apex, elytra distinctly and obliquely truncated at apex, with the
      apical inner angles very sharp in most species (except for H. mulan n. sp.), and
      interval 3 with anterior and posterior setiferous pores (median one lacking). The
      members of Hexachaetus are about 20 species which could be divided into six
      species groups. All except angulatus species group are dealt with in this paper,
      with descriptions of four new species: H. kirschenhoferi n. sp. (Indonesia:
      Kalimantan), H. brunki n. sp. (Malaysia: N. Borneo), H. vietnamensis n. sp.
      (Vietnam: Annam) and H. mulan n. sp. (Malaysia: Perak and Pahang). H. maindroni
      Tian & Deuve, 2006 is proposed as a subspecies of H. lateralis Guerin, 1843, n.
      stat. A key to species groups and species of the genus is also provided.

PMID- 27701290
TI  - Three new brackish-water thalassocypridine species (Crustacea: Ostracoda:
      Paracyprididae) from the Ryukyu Islands, southwestern Japan.
AB  - We describe three new species of brackish-water ostracods representing two genera
      in the ostracod tribe Thalassocypridini from mangrove forests in the Ryukyu
      Islands, subtropical southwestern Japan, and provide their barcoding sequences
      for the mitochondrial cytochrome c oxidase subunit I (COI) gene. Mangalocypria
      ryukyuensis sp. nov. was found on Okinawa Island. We also found a Mangalocypria
      population on Ishigaki Island that was morphologically identical to M.
      ryukyuensis on Okinawa, but an individual differed by 4.7% in COI sequence (K2P
      distance) from an individual from Okinawa. This is the first record for Japan of
      a species in Mangalocypria. Paracypria longiseta sp. nov., obtained from Okinawa
      Island, is similar to Pontoparta hartmanni. Paracypria plumosa sp. nov. from
      Ishigaki Island is similar to Pa. adnata described from Yakushima Island, Japan.
      The COI genetic distance between individuals of Pa. longiseta and Pa. plumosa was
      roughly as large as that between either of these species and individuals in the
      Mangalocypria populations. Our study underscores that genera in Thalassocypridini
      may not represent natural groups, and that this tribe needs taxonomic revision.

PMID- 27701292
TI  - Larva of Glyptotendipes (Glyptotendipes) glaucus (Meigen 1818) (Chironomidae,
      Diptera)-morphology by Scanning Electron Microscope (SEM), karyotype, and biology
      in laboratory conditions.
AB  - Larvae belonging to the family Chironomidae are difficult to identify. The aim of
      the present study was to describe the larval morphology of G. (G.) glaucus with
      the aid of a Scanning Electron Microscope (SEM), the karyotype and biology based
      on materials obtained from laboratory culture. Describing the morphology of
      larvae, special attention was paid to rarely or never described structures like
      the maxilla (lacinia and maxillary palp), the long plate situated below the
      ventromental plate, and plate X situated between lacinia and mentum. The use of
      SEM allowed also to obtain better images of labrum and ventromental plate.
      Morphological features of this species have been supplemented by karyotype and
      biology of larvae in laboratory conditions. Under controlled experimental
      conditions we found non-synchronous development of G. (G.) glaucus larvae hatched
      from one egg mass reflected in different lengths of larvae and emerged imagoes.

PMID- 27701293
TI  - A new species of the genus Corimalia Gozis, 1885 (Coleoptera: Brentidae:
      Nanophyinae) from the Caucasus.
AB  - Corimalia strejceki Schon& Skuhrovec,sp. nov. is described and illustrated from
      the Caucasus, Russia. The new species is compared with the allopatric C. aliena
      (Faust, 1890) differing in size, shape of scales, scale patch close to the
      scutellum, size of mucrones on the meso- and metatibiae, and also shape of the
      apex of the penis. Controversy over the number of segments in the antennae in the
      genus Corimalia is summarized. An annotated catalogue and key of all Corimaliini
      species in the Caucasus is provided.

PMID- 27701294
TI  - Patterns of ecology and distribution of the tree crickets Oecanthus dulcisonans
      and O. pellucens (Orthoptera: Gryllidae; Oecanthinae) in southern Italy.
AB  - Ecological proclivities of the tree cricket Oecanthus dulcisonans, which has been
      recently separated from the well known O. pellucens, have been poorly
      investigated. Moreover, studies on the patterns driving niche segregation between
      these related species are still needed. This study aims to explore the role of
      macro-habitat in shaping the distribution of O. dulcisonans and O. pellucens in
      southern Italy. Occurrence data were sampled by means of a rapid acoustic survey
      scheme at a regional scale. The significance of difference in ecological and
      habitat parameters was tested between the two species. While confirming species
      behavioural patterns, new findings are provided with regard to their ecological
      difference. Species distribution proves to be primarily driven by elevation
      gradient and temperature variation, with O. dulcisonans common and widespread in
      warmer lowlands and O. pellucens limited to higher altitudes. The two species
      also show significant spatial segregation within vegetation layers. These
      findings also provide cues for future studies on species interaction, as well as
      for the assessment of a monitoring scheme which may help interpreting the effects
      of broad environmental changes.

PMID- 27701295
TI  - Sangpradubina, an astonishing new mayfly genus from Thailand (Ephemeroptera:
      Leptophlebiidae: Atalophlebiinae).
AB  - A newly discovered representative of Leptophlebiidae is described and illustrated
      from Thailand as Sangpradubina thailandica, gen. nov. and sp. nov., based on
      larvae and reared adults. This new species presents an interesting transitional
      position, being close to Choroterpes s.l. in the winged stages, but closer to
      Thraulus s.l. in the nymphal stage.   Nymphs are differentiated from those of all
      genera of the Thraulus lineage by the combination of gill I consisting of only a
      single and slender lamella, gills II-VII being fimbriate only in the distal half,
      each mandible having a tuft of setae only in the middle of the lateral margin,
      each maxilla having a well-developed anterolateral projection, fore- and middle
      femora each having a row of long setae on the outer margin, as well as tarsal
      claws having 4 denticles at the base and 9 in the apical position. Adults of the
      new genus barely differ from any genera of the Choroterpes lineage. The egg
      chorionic structure of Sangpradubina also appears to be unusual in that KCT's are
      concentrated on one pole.

PMID- 27701296
TI  - Erratum: ESKANDAR RASTEGAR-POUYANI, SAEED HOSSEINIAN, SOOLMAZ RAFIEE, HAJI GHOLI
      KAMI, MEHDI RAJABIZADEH & MICHAEL WINK (2016) A new species of the genus Eremias
      Fitzinger, 1834 (Squamata: Lacertidae) from Central Iran, supported by mtDNA
      sequences and morphology . Zootaxa, 4132: 207-220.

PMID- 27701297
TI  - Neotropical spittlebugs related to Neaenini (Hemiptera, Cercopidae) and the
      origins of subfamily Cercopinae.
AB  - The Central American tribe Neaenini, originally comprising only the monobasic
      genus Neaenus Fowler, was thought to be transitional between Cercopinae and
      Aphrophorinae. The genus is here enlarged by 5 (1 unnamed)  additional species
      including 2 in a distinctive new subgenus Neaniskus. Keys are presented to 5
      species of Neaenus, to 12 allied Neotropical genera and their 57 species: 12 of
      Tomaspisinella Lallemand, 1927 (=Hemitomaspis Lallemand, 1949, syn.nov. and 3
      distinctive new subgenera Meretricula, Merinx and Merulatomus), 14 species of
      Microsargane Fowler, 1897 (=Ecothera Melichar, 1915, syn.nov., with 2 distinctive
      new subgenera Microrhaphe and Microtholia) and 31 species of Zuata Fennah,
      together with 2 species of Helioptera gen. nov. and 6 monobasic genera
      (Liparonotum gen. nov., Marcion Fennah, Menytes gen. nov., Microclimax gen. nov.,
      Microlaqueus gen. nov. and Simorhina Jacobi). The small Neotropical genera
      Tomaspisina Distant and Olcotomaspis Lallemand (with 2 new combinations and
      subgenus Hyalotomaspis Lallemand, stat.nov.) appear to be allied to the large old
      world genus Phymatostetha Stal rather than to any new-world Cercopinae. A check
      list is presented to these 13 genera and their 76 species (of which 30 are new to
      science and 5 of Zuata are new synonyms). Males are described for 5 species
      previously known from females but males of 9 (in 6 genera) are still unknown.
      Male genitalia define a new tribe of Cercopinae, Microsarganini (Microsargane was
      formerly placed in Aphrophorinae) that also includes Liparonotum, Microclimax and
      Microlaqueus. Almost half of the genera are monobasic without synapomorphies to
      Aphrophorinae, suggesting that these genera (including several genera resembling
      both Aphrophorinae and Cercopinae) represent relict lineages at the base of the
      subfamily Cercopinae.

PMID- 27701298
TI  - Taxonomy of the Mexican species of Thyreocephalus Guerin-Meneville Coleoptera:
      Staphylinidae, Xantholinini).
AB  - Mexican species of Thyreocephalus were analyzed taxonomically based on review of
      125 specimens in eight entomological collections. We propose that T. dugesi
      (Casey, 1906) could be a junior synonym of T. scutellaris (Sharp, 1885), but
      refrain from formal changes until the types can be examined. Thyreocephalus
      arizonicus Smetana, 1982 is recorded for the first time from Mexico in the states
      of Estado de Mexico, Jalisco and Morelos. Currently nine species are recorded
      from Mexico, which is the most species-rich country on the American continent.
      Five closely related species are included in the "puncticeps" species group
      recognized and proposed here. A key for species, supported with illustrations of
      the principal diagnostic structures is provided, as well as redescriptions or
      diagnoses, and taxonomic discussions for each species. Recognized distribution
      patterns are briefly discussed.

PMID- 27701299
TI  - Two new and one redescribed species of Acanthobothrium (Cestoda:
      Onchoproteocephalidea: Onchobothriidae) from Dasyatis akajei (Myliobatiformes:
      Dasyatidae) in the China Sea.
AB  - Acanthobothrium ningdense n. sp. and Acanthobothrium guanghaiense n. sp. are
      described from the spiral intestine of the whip stingray, Dasyatis akajei (Muller
      & Henle). Acanthobothrium ningdense n. sp. is reported based on 38 cestode
      specimens collected at five locations along the Chinese coast, i.e. Taizhou,
      Zhejiang Province, Ningde and Xiamen, Fujian Province, Taishan, Guangdong
      Province and Sanya, Hainan Province between 2012 and 2015. Acanthobothrium
      ningdense n. sp. belongs to the "species category 4" characterised by Ghoshroy &
      Caira. Among category 4 Acanthobothrium species, A. ningdense n. sp. most closely
      resembles A. micracantha Yamaguti, 1952 and A. latum Yamaguti, 1952, both from
      the same host species. Acanthobothrium ningdense n. sp. differs from A.
      micracantha by lacking a long robust hook handle that connects the bases of
      medial and lateral hooks, and from A. latum by having much longer axial prongs
      than abaxial prongs. Acanthobothrium guanghaiense n. sp., only found in Taishan,
      Guangdong Province in 2014, is a category 2 Acanthobothrium species. Among
      category 2, A. guanghaiense n. sp. most closely resembles A. semnovesiculum
      Verma, 1928, but can be differentiated from it by the arrangement of testes (in
      two staggered columns rather than in two tandem columns), and the shape of
      abaxial prong (nearly straight instead of with a conspicuous curve in the
      proximal portion). Acanthobothrium macrocephalum Wang & Yang, 2001 is redescribed
      based on new specimens collected from D. akajei in Guanghai and Sanya. With this
      study, the total number of Acanthobothrium species reported from D. akajei is
      brought to nine. It is possible that some of the species of Acanthobothrium
      previously reported from D. akajei not encountered in this study may have
      geographically restricted distributions, as was observed here for A. guanghaiense
      n. sp..

PMID- 27701300
TI  - An annotated checklist of the Collembolan fauna of Thailand.
AB  - The current knowledge of the Collembolan fauna of Thailand is reported here,
      based on the checklist of Bedos (1994) completed by data on several taxa
      described since this date, with an update of the taxonomic status of the species.
      A total of 194 species from 53 genera and 14 families are listed, that were
      mostly discovered and described during the last three decades. The updated
      checklist illustrates a strong unevenness in sampling efforts across space and
      habitats, and in the degree of taxonomic coverage of the different families of
      the group. Geographically, only the Doi Inthanon massif can be considered as
      relatively well known, but even there the species in several major habitats and
      microhabitats have not been sampled. Data are lacking or much more limited for
      all other regions of the country. The species richness of Thailand is undoubtedly
      much more than observed number.

PMID- 27701301
TI  - On the Nazeris fauna of Zhejiang, China (Coleoptera, Staphylinidae, Paederinae).
AB  - Twelve species of Nazeris Fauvel, 1873 are recorded from Zhejiang, China. Three
      of them are described as new: N. gutianensis Hu & Li, sp. n., N. zhaotiexiongi Hu
      & Li, sp. n., and N. zhangsujiongi Hu & Li, sp. n. Two synonymies are proposed:
      N. minor Koch, 1939 = N. nigritulus Hu, Li & Zhao, 2011, syn. n.; N. chinensis
      Koch, 1939 = N. tianmuensis Hu, Li & Zhao, 2011, syn. n. Nazeris sadanarii Hu &
      Li, 2010 is newly recorded from Zhejiang.

PMID- 27701302
TI  - Acasta sulcata akanthosa, new replacement name for Acasta sulcata spinosa.
AB  - Acasta sulcata spinosa Daniel, 1955 has been discovered to be a junior homonym of
      Acasta spinosa Hiro, 1939. As both names were originally described in the genus
      Acasta, ICZN (International Commission on Zoological Nomenclature) Article 57.2
      defines A. sulcata spinosa as a primary junior homonym, even though it is of
      subspecific nature.

PMID- 27701303
TI  - On the authorship of Austromegabalanus psittacus (Molina).
AB  - Austromegabalanus psittacus is a large, common and economically important
      shoreline barnacle species of the west coast of South America. It was originally
      described by Juan Ignacio Molina as Lepas psittacus, but some confusion has
      arisen as to the exact reference to and year of publication of this species.

PMID- 27701304
TI  - A new synonymy in the genus Macrocixius (Hemiptera: Fulgoromorpha: Cixiidae).
AB  - Until recently the genus Macrocixius Matsumura, 1914 (Hemiptera: Fulgoromorpha:
      Cixiidae) contained two species: M. giganteus Matsumura, 1914 (the type species)
      and M. grossus Tsaur & Hsu, 1991. Two recent papers revised the genus within a
      short interval of time. Both Zhang & Chen (2013) and Orosz (2013) provided
      redescriptions of the genus and its two previously included species; Zhang & Chen
      (2013) described two new species from China; Orosz (2013) described five new
      species from Nepal, Taiwan, Vietnam, and Indonesia.

PMID- 27701305
TI  - First Jurassic grasshopper (Insecta, Caelifera) from China.
AB  - Orthoptera is divided into two suborders, the Ensifera (katydids, crickets and
      mole crickets) and the Caelifera (grasshoppers and pygmy mole crickets). The
      earliest definitive caeliferans are those found in the Triassic (Bethoux & Ross
      2005). The extinct caeliferan families, such as Locustopsidae and Locustavidae,
      may prove to be stem groups to some of the modern superfamilies (Grimaldi & Engel
      2005). Locustopsidae is known from the Late Triassic or Early Jurassic to Late
      Cretaceous, consisting of two subfamilies (Gorochov et al. 2006). They are
      recorded from Europe, England, Russia, central Asia, China, Egypt, North America,
      Brazil and Australia. Up to now, Late Mesozoic fossil deposits of China has been
      reported plenty taxa of orthopterids, e.g. ensiferans, phasmatodeans,
      grylloblattids (Cui et al. 2012; Gu et al. 2010; Gu et al. 2012a; Gu et al.
      2012b; Ren et al. 2012; Wang et al. 2014); but, with few caeliferans records,
      only four species, Pseudoacrida costata Lin 1982, Mesolocustopsis sinica Hong
      1990, Tachacris stenosis Lin 1977 and T. turgis Lin 1980, were reported from the
      Early Cretaceous of Ningxia, Shandong, Yunnan and Zhejiang of China.

PMID- 27701306
TI  - Gluphisia irene, a new species (Lepidoptera, Notodontidae) from China and some
      taxonomical remarks about the palaearctic Gluphisia Boisduval, 1828.
AB  - A new species of Gluphisia irene sp. n., from China's Sichuan Province is
      described. The new species differs in appearance and genitalia from its closest
      relatives, Gluphisia crenata (Esper, 1785), Gluphisia tristis Gaede, 1933 stat.
      n. and Gluphisia meridionalis Kiriakoff, 1963 stat. n. described from Europe and
      China, respectively.

PMID- 27701307
TI  - Zaramillidae, a new amphipod family from the subantarctic Kerguelen Islands
      (Amphipoda, Senticaudata, Gammaroidea, Zaramillidae fam. nov.).
AB  - A new senticaudate amphipod family, Zaramillidae is described from the
      subantarctic Kerguelen Islands, based on the genus Zaramilla Stebbing, 1888. It
      is placed in the gammaridiran amphipods.

PMID- 27701308
TI  - Lithobius (Ezembius) multispinipes n. sp., a new species of centipede from
      NorthWest China (Lithobiomorpha: Lithobiidae).
AB  - The centipede subgenus Lithobius (Ezembius) Chamberlin, 1919 comprises a group of
      about 60 species known from the Near East across Siberia and Central Asia to
      China, and Japan, and Southwards into the Northern Indian subcontinent and the
      Northern part of the Oriental region (Eason 1992, Zapparoli 1999). It is also
      known from Alaska in Western North America (Zapparoli & Edgecombe 2011). Although
      the subgenus was formally proposed as new and described in 1923 (Chamberlin
      1923), according to Jeekel (2005) its name had been already validated in 1919
      (Chamberlin 1919). Ezembius is characterized by the presence of 2+2 or 3+3
      coxosternal teeth, antennal articles fixed at 20 or thereabouts, tergites
      generally without posterior triangular projections and tarsal articulation of
      legs 1-13 distinct (Chamberlin 1923, Zapparoli & Edgecombe 2011).

PMID- 27701309
TI  - New tribe Labiobaetini tribus n., redefinition of Pseudopannota Waltz &
      McCafferty 1987 and descriptions of new and little known species from Zambia and
      Uganda.
AB  - A new tribe Labiobaetini tribus n. is established for a plesiomorphon Labiobaetis
      Novikova & Kluge 1987 and a holophyletic taxon Pseudopannota Waltz & McCafferty
      1987. New synonymy Pseudopannota Waltz & McCafferty 1987 = Ophelmatostoma Waltz &
      McCafferty 1987, syn. n. is proposed. A new species Pseudopannota pannota sp. n.
      closely related to P. berthrandi (Demoulin 1967) is described from Zambia based
      on imagoes of both sexes reared from larvae. Pseudopannota camerunense (Ulmer
      1920) comb. n. is redescribed from Zambia based on imagoes of both sexes reared
      from larvae. A new species Pseudopannota fusca sp. n. is described from Uganda
      based on larvae and subimagoes of both sexes extracted from mature larvae.
      Pseudopannota maculosa (Crass 1947) is reported from Zambia based on larvae.
      Labiobaetis tenuicrinitus (Kopelke 1980) comb. n. (= Baetis spatulatus Gillies
      1994 syn. n.) is redescribed from Uganda based on imagoes of both sexes reared
      from larvae.

PMID- 27701310
TI  - On the genus Aphaobius Abeille de Perrin, 1878, with description of a new species
      from the mesovoid shallow substratum (MSS) of Austria (Coleoptera: Leiodidae:
      Cholevinae: Leptodirini).
AB  - Aphaobius haraldi sp. n. from the mesovoid shallow substratum (MSS) of the
      Austrian Alps is described, illustrated, and compared with the closest species of
      the genus. The new species belongs to the A. kraussi species group, formerly
      including five species. It can be readily separated from other species of the
      genus by the large parameres, with an enlarged apical part, a unique feature
      among species of Aphaobius. The phylogenetic position of the new species is
      clarified using mitochondrial and nuclear data of four related species of
      Aphaobius, plus some representatives of related genera from the same geographic
      area. The diversification of the group was estimated to be recent, dating from
      the Pleistocene. New records and molecular data are provided regarding the
      enigmatic monospecific genus of the Austrian Alps, Lotharia Mandl, 1944, which
      was found to be sister to the studied species of Aphaobius.

PMID- 27701311
TI  - One new genus and three new species of plumulariid hydroids (Cnidaria, Hydrozoa,
      Plumulariidae) from the western Pacific Ocean, with a re-examination of
      Plumularia insignis Allman, 1883 and related taxa.
AB  - One new genus (Schizoplumularia) and three new species (Schizoplumularia
      vervoorti, S. geniculata and S. elegans) of plumulariids are recognized and
      described from large collections of plumularioid hydroids collected in New
      Caledonia and vicinity during several French expeditions. During taxonomic
      studies of these hydroids, colonies were compared with type material of
      Plumularia insignis Allman, 1883 and several other similar species-group taxa. As
      a result, three of the latter (P. flabellum Allman, 1883, P. conjuncta Billard,
      1913, and P. billardi nom. nov.) are recognized as valid in addition to P.
      insignis. The binomen P. billardi is a replacement name for P. insignis var.
      gracilis Billard, 1913. In being elevated to the rank of species in this work, it
      becomes an invalid junior primary homonym of several others having the same name.

PMID- 27701312
TI  - Revision of the Ambrysus hybridus Montandon species complex (Heteroptera:
      Naucoridae: Cryphocricinae) with the description of a new species from Mexico.
AB  - The Ambrysus hybridus Montandon species complex is revised and includes A.
      convexus Usinger, A. fuscus Usinger stat. rev., A. hybridus Montandon, A. lattini
      La Rivers, A. plautus Polhemus & Polhemus, A. spiculus Polhemus & Polhemus, A.
      thermarum La Rivers, and A. ultimus La Rivers. Ambrysus lariversi n. sp. is the
      ninth species in this complex and is described from Mexico. A. tridentatus La
      Rivers and A. woodburyi Usinger are proposed as junior synonyms of A. hybridus
      Montandon and for which a lectotype is designated. Most of the species in this
      complex occur only in Mexico, although A. thermarum is known only from the United
      States and A. hybridus occurs from the southwestern United States to southern
      Mexico and has the widest distribution of any species in this complex. Features
      uniting these species are related to male genitalia and structures associated
      with the male and female genitalia.

PMID- 27701313
TI  - A review of the genus Garra Hamilton 1822 of Bhutan, including the descriptions
      of two new species and three additional records (Cypriniformes: Cyprinidae).
AB  - Seven species of Garra are herein accounted for in Bhutan. Three new records of
      known species, G. arupi, G. birostris, and G. lissorhynchus, and two new species,
      G. bimaculacauda sp. nov. and G. parastenorhynchus sp. nov., are reported from
      central and southern Bhutan. Garra bimaculacauda sp. nov. is most notably
      different from its congeners by the presence of two dark spots on the lobes of
      the caudal fin, having one spot on each lobe. Meristic and morphometric
      differences from northeastern Indian congeners exist as well. Garra
      parastenorhynchus sp. nov. is differentiated from its congeners by the presence
      of a prominent, overhanging, club-shaped proboscis, and a suite of meristic and
      morphometric characters. Notes on the taxonomy are provided for some species.
      Notes are provided on the biology and ecology for most species, which have been
      inferred from field observations. Ranges are expanded for two recently described
      taxa from Northeast India G. arupi, and G. birostris. A key is provided to the
      currently known species of Garra within Bhutan.

PMID- 27701314
TI  - A new species of the genus Rhinoecetes Just, 1983 (Crustacea: Amphipoda:
      Ischyroceridae) from Japan.
AB  - A new species of ischyrocerid amphipods, Rhinoecetes spinicaudus sp. nov., is
      described from Nabeta Bay, southeast coast of Izu Peninsula, central Japan. This
      new species can be distinguished from the other congeners by the presence of
      spinulation on the lateral margins of uropod I rami, row of small robust setae on
      uropod II ramus, and single robust seta on uropod III ramus. More detailed
      distinguishing characters from R. albomaculosus are also discussed. This is the
      first record of the genus Rhinoecetes from Japan. Key to all the species of
      Rhinoecetes is provided.

PMID- 27701316
TI  - A new species of lizard Placosoma Tschudi, 1847 (Squamata: Gymnophthalmidae) from
      the relictual forest mountains of the State of Ceara, Brazil.
AB  - A new species of Placosoma Tschudi, 1847, until now restricted to the Atlantic
      Forest areas of southeastern Brazil is described based on specimens obtained
      about 1700 km north to the current distribution of the genus. Placosoma
      limaverdorum spec. nov. is apparently endemic to three "brejos-de-altitude",
      relictual forest mountains surrounded by dry Caatingas, in the State of Ceara,
      northeastern Brazil. It differs from their congeners by the presence of an
      undivided transparent palpebral disk, a divided nasal scale with a central
      nostril, a deep tympanic recess, a distinctive and thin light vertebral stripe on
      the dorsal surface of the head, body and tail, femoral pores present only in
      males (21-26), preanal pores absent and additionally by having 21-24 rows of
      transverse ventral scales, 34-38 dorsals, dorsal, lateral and ventral scales
      smooth, dorsal scales quadrangular, longer than wide, except in the neck region,
      where they are wider than long.

PMID- 27701315
TI  - Squalius namak, a new chub from Lake Namak basin in Iran (Teleostei: Cyprinidae).
AB  - Squalius namak, new species, from the endorheic Lake Namak and Kavir basins in
      Iran, is distinguished from the species of the genus Squalius in the Persian Gulf
      and the southern Caspian Sea basins by having a wide and thick symphysial knob on
      the lower jaw, a convex posterior anal-fin margin, a bold, dark-grey or brown,
      roundish or crescent-shaped blotch at the posterior tip of each flank scale and
      orange caudal-, anal- and pelvic-fin rays in life. Squalius namak is also
      characterized by four fixed, diagnostic nucleotide substitutions in the mtDNA COI
      barcode region.

PMID- 27701317
TI  - Two new species of Loboschiza from Cambodia and Vietnam (Lepidoptera:
      Tortricidae: Olethreutinae: Enarmoniini).
AB  - Two new species of Loboschiza are described and illustrated: L. cambodiensis n.
      sp., from Cambodia and L. flavobasis n. sp., from Vietnam. The two new species
      bring the number of described species in the genus to 19.

PMID- 27701318
TI  - A new Peritrich Ciliate from a Hypersaline Habitat in Northern China.
AB  - A new peritrichous ciliate, Cothurnia salina n. sp., collected from a brine pond
      of a salt factory in Yantai, China, was investigated based on live observations,
      silver staining method and molecular phylogenetic analysis. The diagnosis for
      this new taxon: body elongated columnar, in vivo 80-98 * 12-19 um; lorica barrel
      shaped, with aboral part heavily thickened; stalk extremely short, with
      approximately 1/2 of its length within the lorica; macronucleus wormlike,
      longitudinally oriented; single contractile vacuole ventrally located; pellicle
      with conspicuous parallel transverse striations, 62-73 from aboral trochal band
      to peristome and 32-38 from aboral trochal band to scopula; infundibular
      polykinety 3 (P3) consisting of two ciliary rows, which are equal length,
      parallel to each other and terminate adstomally between P1 and P2. Small subunit
      (SSU) rRNA gene trees revealed that the new species clustered with other members
      of the family Vaginicolidae as expected.

PMID- 27701319
TI  - A new species of Holotachysphex de Beaumont, 1940 (Hymenoptera, Apoidea,
      Crabronidae) from Iran with identification key to species.
AB  - Holotachysphex iraniensis sp. nov. (Hymenoptera, Apoidea, Crabronidae) from
      southern Iran is described. A revised key to the world species of Holotachysphex
      is provided. A red form of H. mochii from Jordan is described.

PMID- 27701320
TI  - Taxonomic review of the Genus Tautoneura Anufriev (Hemiptera: Auchenorrhyncha:
      Cicadellidae: Typhlocybinae) from Korea, with description of one new species.
AB  - One new species of the genus Tautoneura, T. polymitusa sp. nov., is described,
      and T. tricolor Anufriev, 1969 and T. japonica (Dworakowska, 1972) are reported
      from Korea for the first time. Descriptions, illustrations and a key to the
      Korean Tautoneura species are provided.

PMID- 27701322
TI  - The Steninae MacLeay, 1825 (Coleoptera: Staphylinidae) of Iran: identification
      key, checklist of species and a new synonymy.
AB  - In this contribution to the knowledge of the Steninae MacLeay, 1825 of Iran we
      present an identification key to the 69 species known to occur in this country,
      which includes illustrations of the diagnostic genital characters of all species
      involved. The endophallic characters of the aedeagus of several Iranian species
      of Stenus Latreille, 1797 are illustrated for the first time. A critical
      checklist of the Steninae of Iran is presented at the province level. Stenus
      alanorum Ryvkin, 1990 is synonymized with S. medus Puthz, 1981.

PMID- 27701321
TI  - Additional new species of the genus Obolopteryx Cohn et al. 2014 (Ensifera:
      Tettigoniidae) from Northeastern Mexico.
AB  - The present contribution describes five new species of Phaneropterinae from
      Northeastern Mexico: Obolopteryx eurycerca n. sp., Barrientos-Lozano & Rocha
      Sanchez, O. nigra n. sp., Barrientos-Lozano & Rocha-Sanchez, O. tamaholipana n.
      sp., Barrientos-Lozano & Rocha-Sanchez, O. huastecana n. sp., Barrientos-Lozano &
      Rocha-Sanchez, and O. tanchipae n. sp., Barrientos-Lozano & Rocha-Sanchez.
      Diagnostic characters are illustrated and information on distribution and ecology
      provided. Polymorphism and geographic variation of the genus Obolopteryx Cohn et
      al. 2014 are discussed.

PMID- 27701323
TI  - Onuphis and Mooreonuphis (Annelida: Onuphidae) from West Africa with the
      description of three new species and the reinstatement of O. landanaensis
      Augener, 1918.
AB  - The taxonomy of eastern Atlantic species of the genus Onuphis has been confused
      due to the somewhat cursory and misleading descriptions of species and the
      disregard of the true identity of the type species of the genus, O. eremita,
      which has been commonly reported from West Africa, along with O. geophiliformis
      and O. rullieriana. However, all three species are now considered as unlikely to
      occur in western Africa. This work recognises three species of Onuphis from this
      region. Two of them, Onuphis augeneri sp. nov. and O. hanneloreae sp. nov., are
      newly described from Nyanga estuary (Gabon) and Sal Island (Cape Verde)
      respectively. Furthermore, Onuphis landanaensis, a species described from the
      Gulf of Guinea and subsequently synonymised with O. eremita, is formally
      reinstated and redescribed based upon the re-examination of the original types.
      Detailed descriptions and illustrations of all species are presented as well as
      the ontogenetic changes of the brooder O. hanneloreae sp. nov. Furthermore, the
      genus Mooreonuphis is recorded for the first time in Africa with the description
      of M. nunezi sp. nov. from Cape Verde archipelago. Additionally, a dichotomous
      key to all species of the genera Onuphis and Mooreonuphis from the eastern
      Atlantic is included.

PMID- 27701324
TI  - Cladorhiza corallophila sp. nov., a new carnivorous sponge (Cladorhizidae,
      Demospongiae) living in close association with Lophelia pertusa and Madrepora
      oculata (Scleractinia).
AB  - In this study, we describe a new species of cladorhizid sponge, which shows a
      very peculiar mode of life: It always occurs in association with the
      scleractinian cold-water corals Lophelia pertusa and Madrepora oculata. Although
      the sponge lives in nutrient-rich areas, we document its carnivorous feeding
      behavior. The identity of the new species was verified using molecular markers:
      the species is very closely related to the North-Atlantic Cladorhiza abyssicola,
      but it differs distinctly, and forms a monophyletic clade. The two species might
      be considered very close relatives, probably sister species deriving from a
      common ancestor.

PMID- 27701326
TI  - Description of two new species of Seinura Fuchs, 1931 (Nematoda:
      Aphelenchoididae) from Iran.
AB  - Two new species of Seinura are described and illustrated using both morphological
      and molecular characters. Seinura persica n. sp. is characterized by having
      females with a distinct cephalic region, stylet 19.5 (18-20) MUm long, four
      incisures in the lateral fields, position of excretory pore anterior to the base
      of metacorpus, post-uterine sac 54.8 (50-60) MUm long, and an elongate-conoid
      tail with a shallow depression on the dorsal side ending in a sharply pointed
      tip. Males have body length of 467 and 592 MUm, spicules 15 and 16 MUm long with
      a prominent triangular-shaped rostrum, developed condylus and no cucullus.
      Seinura hyrcania n. sp. is characterized by having an offset lip region, stylet
      21.5 (18-24) MUm long, three incisures in the lateral fields, excretory pore
      anterior to the base of the metacorpus, post-uterine sac 19 (12-25) MUm long and
      conical tail ending in a filiform terminus. Morphological and morphometric
      diagnostic characters together with molecular data based on partial sequences of
      SSU and LSU of the ribosomal DNA gene are provided for these new species.

PMID- 27701325
TI  - Occurrence of Epistylis anastatica (Linnaeus, 1767) (Ciliophora: Peritrichia) on
      Mesocyclops isabellae Dussart & Fernando (Crustacea: Copepoda: Cyclopoida) in
      India, with an annotated checklist of species of Epistylis reported as Epibionts
      of Cyclopoid Copepods and resources for their identification.
AB  - The colonial peritrich ciliate Epistylis anastatica (Linnaeus, 1767) was
      discovered living as an epibiont on Mesocyclops isabellae Dussart & Fernando,
      1988 collected from a pond in Andhra Pradesh state, India. This is the first
      report of Epistylis on this host, and a description of its morphological
      characteristics is provided. The biomass of colonies of E. anastatica relative to
      that of their hosts was relatively high, being greater than that of the host in
      some cases (8.11 mm<sup>3</sup> vs. 1.14 mm<sup>3</sup> or less), and this
      epibiotic burden has the potential to have an impact on the host's activities.
      Relationships between epibiotic peritrichs and microcrustaceans like cyclopoid
      copepods may be much more complex than previously supposed and merit more
      thorough investigation. Species of Epistylis are commonly found on cyclopoid
      copepods, but resources for taxonomic identification are limited and scattered;
      therefore, an annotated checklist of all species reported from cyclopoid copepods
      and a summary of the diagnostic characteristics of each one is provided as an aid
      to investigators. Some records of Epistylis spp. from cyclopoid copepods that are
      accompanied by documentary evidence are misidentifications, raising the suspicion
      that many other undocumented records also may be erroneous; therefore, it is
      suggested that authors provide supplementary descriptions and figures.

PMID- 27701327
TI  - Three new species of the genus Ricanula Melichar, 1898 (Hemiptera: Fulgoromorpha:
      Ricaniidae) from China.
AB  - Three new species of the genus Ricanula Melichar, 1898: R. unica sp. nov., R.
      fujianensis sp. nov. and R. hainanensis sp. nov. are described from south China.
      An identification key to Ricanula species in Chinese fauna is provided.
      Photographs of the adults and illustrations of genital structures of the new
      species are also given.

PMID- 27701328
TI  - Comments on the morphology and biology of Pammene castanicola Trematerra &
      Clausi, 2009 (Lepidoptera: Tortricidae: Grapholitini).
AB  - Many insects are reported to damage cultivated chestnut (Castanea sativa Mill.;
      Fagaceae) in Italy, but the most important pests of chestnut fruits are weevils
      (Curculio elephas Gyll. and Curculio glandium Marsh.; Curculionidae) and
      tortricid moths (Pammene and Cydia; Tortricidae) (Pollini, 1998, Speranza, 1999).
      The larvae of the tortricid pests develop internally, tunnelling in the fruits
      and eating the endocarp (Rotundo et al. 1991), which significantly reduces nut
      quality and commercial value. The most damaging tortricid moths in the Italian
      chestnut industry are Pammene fasciana (Linnaeus) (the early chestnut moth),
      Cydia fagiglandana (Zeller) (the intermediate chestnut moth), and Cydia splendana
      (Hubner) (the late chestnut moth) (Pedrazzoli et al. 2012). Pammene castanicola
      Trematerra & Clausi, 2009 was recently described from chestnut woods near Etna
      Vulcan, Sicily (Trematerra and Clausi 2009), and it is known only from the
      vicinity of the type locality. It is similar to Pammene fasciana in morphological
      and biological features, and it was previously misidentified as P. fasciana. We
      provide observations on the biology and larval development and present detailed
      descriptions and illustrations of the mature larva of P. castanicola, with
      comments on the differences between P. castanicola and P. fasciana.

PMID- 27701330
TI  - Megatibicen n. gen., a new North American cicada genus (Hemiptera: Cicadidae:
      Cicadinae: Cryptotympanini).
AB  - The genus Tibicen has had a confusing history (see summary in Boulard and
      Puissant 2014; Marshall and Hill 2014; Sanborn 2014). Boulard and his colleague
      (Boulard 1984; 1988; 1997; 2001; 2003; Boulard and Puissant 2013; 2014; 2015)
      have argued for the suppression of Tibicen and the taxa derivatived from it in
      favor of Lyristes Horvath. Boulard's argument for suppression was first described
      in Melville and Sims (1984) who presented the case for suppression to the
      International Commission on Zoological Nomenclature with further comments made by
      Hamilton (1985), Boulard (1985), and Lauterer (1985). A lack of action resulted
      in additional comments being published in 2014 again supporting the retention
      (Sanborn 2014; Marshall and Hill 2014) or the suppression (Boulard and Puissant
      2014) of Tibicen.

PMID- 27701329
TI  - Morphological similarities between Amphisbaena mitchelli Procter, 1923 and A.
      miringoera Vanzolini, 1971 (Squamata: Amphisbaenidae): phylogenetic relatedness
      or morphological convergence?
AB  - To date, 22 species of amphisbaenids have been recorded at Brazilian Amazon
      (Ribeiro et al. 2008), six of them are small and have two pre-cloacal pores
      (Hoogmoed & Avila-Pires 1991; Teixeira Jr. et al. 2014). Most of these species
      have narrow distributions, and its biology and phylogenetic relationships are
      poorly understood (Hoogmoed & Avila-Pires 1991). Amphisbaena mitchelli Procter,
      1923 and A. miringoera Vanzolini, 1971 share several morphological similarities
      that could reflect phylogenetic relatedness (Vanzolini 1971). Both have two pre
      cloacal pores and a similar pattern of head scutelation, but whereas the first
      has 193-220 and 26-29 body and tail annuli, respectively, the latter has 250-264
      and 22-24 (Vanzolini 1971).

PMID- 27701331
TI  - A second species, and first Central American record, of the phorid fly genus
      Lenkoa Borgmeier (Diptera: Phoridae).
AB  - A second species, and first Central American record, of the phorid fly genus
      Lenkoa Borgmeier (Diptera: Phoridae). Many species of phorid flies have wingless
      or brachypterous females. Mostly, they belong to a group classified within the
      subfamily Metopininae corresponding to the Metopina group of genera of Brown
      (1992a) or the tribe Metopinini of Disney (2003, not 1987). The males of this
      group are much more typical in appearance, with well-developed wings, larger
      eyes, and fully developed abdominal tergites. These males carry females during a
      mating flight, often dispersing them to new breeding sites (Miller 1984).
      Generally, the sexual dimorphism is so great that the sexes cannot be confidently
      associated unless they are collected in copula. This has led to a profusion of
      species being described as males and females in separate genera. Some of these
      brachypterous females, both within the Metopinini and elsewhere in other
      Phoridae, have been correctly associated with their males when they are found
      together (e.g., Brown 1986, 1992b, 1994), but many remain unassociated.

PMID- 27701332
TI  - Revised status of Oridryas Meyrick, 1938: new synonyms of Ypsolopha Latreille,
      1796, and Ypsolopha parenthesella (Linnaeus, 1761 (Yponomeutoidea: Ypsolophidae).
AB  - The eminent entomologist Aristide Caradja (1861-1955) published between 1925 and
      1939, on his own or jointly with Edward Meyrick, a series of taxonomic papers on
      Chinese microlepidoptera including the descriptions of 18 new species in
      Yponomeutidae (Hyponomeutidae of authors). Their type specimens are currently
      deposited in two institutions, the Natural History Museum in London (BMNH:
      formerly British Museum of Natural History), as previously incorporated in the
      Meyrick collection, and the "Grigore Antipa" National Museum of Natural History
      in Bucharest, Romania (MGAB), as incorporated in the Caradja collection. The BMNH
      specimens were examined and illustrated by Clarke (1965). The type specimens of
      Oridryas kept in MGAB have never been studied since the original descriptions.

PMID- 27701333
TI  - A new river loach from the main channel of the upper Mekong in Yunnan
      (Cypriniformes: Nemacheilidae).
AB  - Nemacheilid loaches are a common element of fish assemblages of Southeast Asian
      streams. In particular, streams in tropical and subtropical regions with a
      gravelly to rocky substrate and a swift current are typically inhabited by
      several species of nemacheilid loaches. Up to six different species are reported
      to occur syntopically (Kottelat 1990). The vast majority of these loaches are
      allocated within the diverse genus Schistura, which accommodates about 200 valid
      species (Kottelat 2012). River loaches of the genus Schistura are defined as
      having the mouth moderately arched; the lower lip medially notched, not forming
      lateral labial pads; air bladder without a secondary chamber, and a maximum size
      between 25 mm and 120 mm SL (Kottelat 1990).

PMID- 27701334
TI  - Revising Australian Pristomerus (Hymenoptera, Ichneumonidae, Cremastinae):
      species with a tooth on the hind femur.
AB  - The Australian insect fauna is among the least-well studied in the world, and
      conservative estimates state that 75% of the species still await description. In
      the more species-rich groups, this percentage might be even larger, which is
      certainly the case in parasitoid wasps which have received very little attention
      by taxonomists. The genus Pristomerus of the family Ichneumonidae is distributed
      worldwide, with most species found in the tropics. Its members attack concealed
      larvae of small Lepidoptera, and several species are used in biocontrol. Five
      species have been reported from Australia, all of them endemic, but many more
      undescribed species are present in various collections. I here revise Australian
      Pristomerus, focussing on the species that bear a tooth on the ventral side of
      the hind femur. Twenty-two species are recorded, 19 of which are described as
      new: Pristomerus australiensis n. sp., P. bertschmanni n. sp., P. callitrinus n.
      sp., P. dundeei n. sp., P. flavicephalus n. sp., P. fourecksensis n. sp., P.
      gracilis n. sp., P. kakaduensis n. sp., P. laetus n. sp., P. luculentus n. sp.,
      P. lunatus n. sp., P. mangiferus n. sp., P. merus n. sp., P. nedkellyi n. sp., P.
      pellicius n. sp., P. periculosus n. sp., P. stellatus n. sp., P. tenebrosus n.
      sp., and P. venustus n. sp. A dichotomous key and an online interactive key to
      the known Australian species with a tooth on the hind femur are provided,
      including photographs of all the species. The origin of the considerable number
      of Australian Pristomerus species remains unclear. They might represent Southern
      relict elements with affinities to South American taxa, or their ancestors might
      have immigrated from the Paleotropics in more recent times; this question can
      only be solved with a dated phylogeny of the genus. However, support for a
      Palaeotropic origin of at least a good portion of the taxa comes from their
      current distribution, as the Australian Pristomerus are found to be most diverse
      in the tropical habitats of Northern Queensland and the Northern Territories.

PMID- 27701335
TI  - Many things come in small packages: Revision of the clawless geckos
      (Crenadactylus: Diplodactylidae) of Australia.
AB  - We provide a taxonomic revision of the genus Crenadactylus, a group of very small
      clawless geckos from western and central Australia, with currently only one
      recognized species and four subspecies. Morphological comparisons were made on
      genotyped specimens from two recent genetic studies, then with an expanded sample
      to encompass all specimens to determine diagnostic characters in addition to
      morphological and geographic boundaries. Based on our findings, we elevate the
      subspecies Crenadactylus ocellatus ocellatus from south-western Australia and C.
      o. horni from the Central Uplands to full species. Consultation of the types of
      Diplodactylus (= Crenadactylus) bilineatus indicate they are C. ocellatus based
      on a dorsal pattern with intermixing of dark and pale scales not shared with any
      other taxa; we therefore maintain synonymy of 'D.' bilineatus with 'D.'
      ocellatus. We describe three new Western Australian species formerly allocated to
      C. o. horni: C. occidentalis sp. nov. from the western coast, C. tuberculatus sp.
      nov. from the Cape Range and C. pilbarensis sp. nov. from the Pilbara region. To
      stabilize the Kimberley taxa, we also raise C. ocellatus rostralis and C.
      ocellatus naso, both monophyletic taxa from the monsoonal tropics, to full
      species, while acknowledging further work is required on the C. naso species
      complex. All new species treated here possess distinctive morphological
      characters to diagnose them, including enlarged dorsal tubercles in C.
      tuberculatus sp. nov., a single enlarged supranasal in C. horni and a single
      enlarged postmental in C. pilbarensis sp. nov. Pattern was relatively conserved
      among taxa, with highly  contrasting dark and pale longitudinal lines, with the
      exception of the type species C. ocellatus that possesses intermixed dark and
      pale scales and ocelli. Crenadactylus species are separated by deep genetic
      divergences and are usually allopatrically distributed. This indicates that
      despite being Australia's smallest geckos, or possibly because of it, these
      diminutive lizards have a long history of localised persistence through major
      climatic changes over millions of years.

PMID- 27701336
TI  - New and little-known species of the genus Lacon Laporte, 1838 (Coleoptera:
      Elateridae) of Afghanistan and adjacent countries.
AB  - Two new species of the genus Lacon Laporte, 1838 are described: L. elegantissimus
      sp. nov. (Afghanistan, India) and L. kabakovi sp. nov. (Afghanistan). L.
      caeruleus Schimmel, 1998 is recorded for the first time in Afghanistan, presence
      of L. funebris (Solsky, 1881) in Afghanistan is confirmed. In addition, some
      taxonomic and morphological notes on the Lacon species of Afghanistan and
      adjacent countries are given.

PMID- 27701337
TI  - On the vesica of Eucosmini and Grapholitini (Insecta: Lepidoptera: Tortricidae).
AB  - Eucosmini and Grapholitini are highly specialised and closely related tribes of
      the subfamily Olethreutinae of the family Tortricidae. Previous studies have
      shown that there is considerable similarity in the general shape of the everted
      vesica and structure of cornuti in these two tribes. In this study the possible
      function of the vesica during copulation is discussed based on everted vesicae of
      intact specimens treated with dichlorvos, a compound that causes eversion of the
      vesica and formation of the spermatophore. A comparison between chemically and
      mechanically everted vesicae showed that the vesica consists of two functionally
      different parts: an eversible and a non-eversible. Clear distinction in the
      position and function of deciduous and non-deciduous cornuti was observed; non
      deciduous cornuti are attached to the eversible part of the vesical and the
      deciduous cornuti to the non-eversible part. The mechanism of detachment of
      deciduous cornuti was revealed. Some peculiarities of the possible interaction
      between male and female genitalia are discussed.

PMID- 27701338
TI  - First occurrence of Nemobiinae crickets in the Lesser Antilles (Orthoptera,
      Grylloidea, Trigonidiidae), with the descriptions of three new species.
AB  - The occurrence of Nemobiinae crickets (Grylloidea, Trigonidiidae) in the Lesser
      Antilles is attested here for the first time, by the descriptions of three new
      species of Absonemobius Desutter-Grandcolas, 1993 from Guadeloupe, St. Lucia and
      St. Vincent: Absonemobius septentrion n. sp., Absonemobius lucensis n. sp. and
      Absonemobius vincenti n. sp., and the discovery of Hygronemobius Hebard, 1913 in
      Guadeloupe. The generic attribution of several nemobiine species described from
      the Caribbean and from Southern Central America are also reviewed: Nemobius
      elegans Otte, 2006 from Costa Rica and Pteronemobius sanaco Otte & Perez
      Gelabert, 2009 described from Belize are transferred to Hygronemobius;
      Hygronemobius darienicus Hebard, 1913 described from Panama is transferred to
      Absonemobius Desutter-Grandcolas, 1993; Hygronemobius epia Otte & Perez-Gelabert,
      2009 does not belong to Hygronemobius, but is temporarily kept in this genus as
      incertae sedis.

PMID- 27701339
TI  - Redescription of two troglobiotic species of Deuteraphorura Absolon, 1901 <br
      />(Collembola, Onychiuridae) from the Western Carpathians.
AB  - Two species of the genus Deuteraphorura Absolon, 1901 from the Western Carpathian
      caves (Central Europe) are redescribed, namely D. kratochvili (Nosek, 1963) and
      D. schoenviszkyi (Loksa, 1967). Both species are characterized by the absence of
      pseudocelli on thoracic tergum I, presence of male ventral organ on abdominal
      terga II-III and 3 pseudocelli on hind margin of head. D. kratochvili is
      redescribed based on specimens from the type locality (Demanovska Cave System)
      and its intraspecific variability in morphological traits is discussed.
      Redescription of D. schoenviszkyi (Loksa, 1967) is based on specimens from the
      Slovak and Aggtelek Karst, the karst area where the type locality is situated.
      Both species are restricted to subterranean environment, thus classified as
      obligate cave forms (troglobionts). An identification key to Deuteraphorura
      species, characterized by absence of pseudocelli on thoracic segment I, is
      provided.

PMID- 27701341
TI  - New records of doryctine wasps (Hymenoptera: Braconidae) from Argentina, with the
      description of Shawius diiorioi Martinez sp. nov.
AB  - New distributional records of the genera Fritziella Marsh, Rhoptrocentrus
      Marshall and Shawius Marsh are reported. Fritziella plaumanni Marsh,
      Rhoptrocentrus piceus Marshall and Shawius braziliensis Marsh are newly reported
      from northern Argentina. Shawius diiorioi Martinez sp. nov. is described and
      illustrated from central and northern Argentina. The male of Shawius, previously
      unknown, is described and illustrated for the first time. All species were reared
      from Fabaceae and Celtidaceae infested by wood boring Coleoptera.

PMID- 27701340
TI  - Redescription, lectotype designation and new records of Anastrepha luederwaldti
      Lima (Diptera, Tephritidae).
AB  - The previously poorly known species Anastrepha luederwaldti Lima, 1934 is
      redescribed based on a reexamination of the syntypes from Sao Paulo and
      additional specimens from Santa Catarina and Rio Grande do Sul, Brazil. A
      lectotype is designated.

PMID- 27701342
TI  - A Revision of the Pseudotropheus elongatus species group (Teleostei: Cichlidae)
      With Description of a New Genus and Seven New Species.
AB  - Lake Malawi is known for its endemic haplochromine species flock, most notably
      the rock-dwelling cichlids known as mbuna. The group of mbuna referred to as the
      Pseudotropheus elongatus species group is currently comprised of Metriaclima
      spp., Tropheops spp., Cynotilapia spp., and Pseudotropheus spp. In this study,
      Chindongo, a new genus with the type species C. bellicosus, is described for
      additional species in this group. Chindongo is distinguished from other mbuna
      genera by 1) the presence of bicuspid teeth in the anterior portion of the outer
      row of both upper and lower jaw; 2) a moderately to steeply sloped vomer with a
      narrow rostral tip which makes an angle of between 53 degrees  and 68 degrees 
      with the parasphenoid; 3) a small mouth with the lower jaw slightly shorter than
      the upper; 4) a broad anterior dentigerous area on both premaxilla and dentary
      with three or more rows of teeth (usually 5-6 rows); 5) a flank melanin pattern
      consisting of vertical bars without horizontal elements at any stage of
      development. Chindongo bellicosus is distinguished by its color pattern and
      shallower body from the other species which we have transferred to Chindongo. We
      also describe six new elongate mbuna species and place them into three available
      genera, they include: Metriaclima flavicauda, M. usisyae, Tropheops kumwera, T.
      biriwera, T. kamtambo, and Cynotilapia chilundu.

PMID- 27701343
TI  - Two new species of genus Lasiosina Becker from China (Diptera, Chloropidae).
AB  - A review of the species of the genus Lasiosina Becker from China is provided. The
      following two species are described as new to science: L. nigrolineata sp. nov.
      and L. recurvata sp. nov. A key to all species of Lasiosina from China is given.

PMID- 27701344
TI  - A new species of Rhyacophila (Trichoptera: Rhyacophilidae) and new records of
      Trichoptera from Asia.
AB  - A new species of the Rhyacophila scissa Group (Trichoptera, Rhyacophilidae),
      Rhyacophila huesunensis n. sp. from Taiwan (Republic of China), is described and
      illustrated with drawings of the genitalia. Also, new records of eight caddisfly
      species from Asia are presented.

PMID- 27701345
TI  - Menieroclerus gen. nov.: A new genus for Thanasimodes nigropiceus (Kuwert, 1893)
      (Coleoptera: Cleridae: Clerinae).
AB  - Opilo nigropiceus Kuwert was described from a specimen collected in Bagamoyo on
      the north coast of Tanzania, though the description was devoid of informative
      morphological detail (Kuwert 1893). Without comment, Schenkling (1915)
      transferred O. nigropiceus to Thanasimodes Murray, a genus erected by Murray
      (1867) for a single specimen from 'Old Calabar' (south Nigeria) described as
      Thanasimodes metallicus Murray. Thanasimodes presently contains ten species and
      is distributed widely throughout Africa, from South Africa to the northernmost
      countries (Corporaal 1950; Gerstmeier 1998).

PMID- 27701346
TI  - Worldwide revision of the genus Fraseroscyphus Boero and Bouillon, 1993
      (Cnidaria: Hydrozoa): an integrative approach to establish new generic diagnoses.
AB  - The morphological character of the hydrocladium and gonotheca origin from within
      the hydrothecal cavity has rarely been applied for generic diagnoses in
      hydrozoans. Its taxonomic value has been controversial for more than a century.
      The genus Fraseroscyphus Boero and Bouillon, 1993 (Hydrozoa: Sertulariidae) is a
      relatively recently debated case and it has been distinguished from
      Symplectoscyphus Marktanner-Turneretscher, 1890 based on this character. A review
      of this character in all published nominal species of the family Sertulariidae
      reveals that its occurrence is inconsistent at the genus level. However,
      phylogenetic analyses based on mitochondrial (16S) and nuclear (18S, 28S) genes
      support the position of Fraseroscyphus as a genus within the family
      Symplectoscyphidae Maronna et al., 2016. Comparisons of 16 morphological
      characters of 10 related species support the distinction of Fraseroscyphus from
      Antarctoscyphus and Symplectoscyphus by other characters in addition to the
      hydrocladial and gonothecal origin character. These new characters include the
      rarely-branched hydrocaulus, the absence of an apophysis, and the absence of an
      axillary hydrotheca. Furthermore, a revision based on the morphological character
      complex mentioned above using type and topotypic material, demonstrated that
      Sertularella sinuosa Fraser, 1948 (type species of Fraseroscyphus) and
      Symplectoscyphus huanghaiensis Tang & Huang, 1986 are junior synonyms of F.
      hozawai (Stechow, 1931) comb. nov. The assignment of Sertularella irregularis
      Trebilcock, 1928 and Sertularella macrogona Trebilcock, 1928 to Fraseroscyphus is
      also supported. In addition, sequence polymorphism of mitochondrial genes even
      within a single hydroid fragment was detected by the molecular cloning method,
      and is probably in part attributable to errors introduced by PCR, mitochondrial
      heteroplasmy and/or nuclear mitochondrial DNA (NUMTs). The adoption of the
      cloning method may be crucial to improve the sequence accuracy for some colonial
      hydrozoans.

PMID- 27701347
TI  - Phylogeny and genetic variation within the widely distributed Bluntnose Minnow,
      Pimephales notatus (Cyprinidae), in North America.
AB  - This study represents a phylogenetic analysis of Pimephales notatus, a widely
      distributed North American cyprinid fish species, using one mitochondrial (cytb)
      and two nuclear (S7 and Rag1) genes. Despite the broad geographic distribution of
      this species that includes independent basins, results suggest a largely drainage
      independent genetic structure. Results reveal a well-supported lineage in the
      Ozark Highlands, which is highly divergent from the remaining populations and may
      represent a long-term isolated lineage that should be considered as a separate
      conservation and management unit. All other remaining populations comprised a
      widely distributed lineage, covering most of the distribution for the species
      (from the Red River and tributaries of the Great Lakes in the north to the lower
      Mississippi and Mobile basin in the south, and from the Missouri River in the
      west to the Chesapeake and Albemarle Sound basins in the east). Phylogenetic,
      genetic diversity, and biogeographical data suggest that this wide-ranging
      lineage could have experienced a recent expansion to northern areas where
      populations exhibit little genetic variation. Results from molecular analyses
      reveal a distinctive lineage in the Ozarks and suggest that there is need for
      morphological analyses within P. notatus to determine its taxonomic status.

PMID- 27701349
TI  - Cnemaspis rajakarunai sp. nov., a rock dwelling day-gecko (Sauria: Gekkonidae:
      Cnemaspis) from Salgala, an unprotected lowland rainforest in Sri Lanka.
AB  - A new species of Cnemaspis, Cnemaspis rajakarunai sp. nov. is described and is
      the fourth rock dwelling species belonging to the genus known from Sri Lanka. The
      new species is readily distinguished from all other congeners by the following
      combination of characters: adult snout-vent length 36-40 mm; precloacal pores
      absent, large femoero-precloacal scales 22; femoral pores 7-8, enlarged femoral
      scales 6; ventral scales 146-186; supralabials (to midorbital position) 7;
      supralabials (to angle of jaws) 9; total lamellae on finger IV 19-22, shape of
      the basal lamellae on toe IV elliptical; and its unique colour pattern. The new
      species is recorded from Salgala Forest an unprotected lowland rain forest.

PMID- 27701348
TI  - A taxonomic monograph of the leaf-litter inhabiting weevil genus Plumolepilius
      new genus (Coleoptera: Curculionidae: Molytinae: Conotrachelini) from Mexico,
      Guatemala, and El Salvador.
AB  - We describe the Mesoamerican leaf litter weevil genus Plumolepilius Barrios-Izas
      & Anderson, new genus (Coleoptera: Curculionidae: Molytinae: Conotrachelini)
      (type species P. trifiniensis Barrios-Izas & Anderson, new species), species of
      which inhabit mountain ecosystems from the state of Chiapas in southeastern
      Mexico to northern Panama. In this paper we describe nine new species from
      Mexico, Guatemala, and El Salvador: P. trifiniensis Barrios-Izas & Anderson, new
      species (El Salvador and Guatemala); P. branstetteri Barrios-Izas & Anderson, new
      species (Guatemala and Mexico); P. longinoi Barrios-Izas & Anderson, new species
      (Guatemala and Mexico); P. cortezi Barrios-Izas & Anderson, new species
      (Guatemala and Mexico); P. canoi Barrios-Izas & Anderson, new species
      (Guatemala); P. schusteri Barrios-Izas & Anderson, new species (Guatemala and
      Mexico); P. daryi Barrios-Izas & Anderson, new species (Guatemala); P.
      yolnabajensis Barrios-Izas & Anderson, new species (Guatemala); and P.
      macalajauensis Barrios-Izas & Anderson, new species (Guatemala). The genus and
      the species are named and described, information on their geographical
      distributions is given and images of the habitus of both sexes and the aedeagus
      are presented. A key to the species of Plumolepilius based on males is included.
      The monophyly of Plumolepilius was confirmed by a parsimony analysis of external
      and male aedeagus morphology and the genus is best characterized by the presence
      of plumose scales lining the prosternal channel. Phylogenetic analysis supports
      that Lepilius Champion 1905 is the sister genus of Plumolepilius.

PMID- 27701350
TI  - The Oncometopia orbona species group (Hemiptera, Cicadellidae, Proconiini).
AB  - The Oncometopia orbona group of species is defined based on the characteristic
      structure of the male aedeagus. A key to males and females of 9 species is
      included, among which 5 are newly described from the U.S.A., Mexico, and Central
      America: O. orbona (F.), O. nigricans (Walker), O. obtusa (F.), O. clarior
      (Walker) (= Proconia badia Walker syn. n., Proconia scutellata Walker synonymy
      reinstated), O. hamiltoni sp. n., O. acicularis sp. n., O. lepida sp. n., O.
      pelvica sp. n., and O. unispina sp. n. The systematics of the group presents some
      unusual cases. In particular, O. lepida sp. n. and O. pelvica sp. n. differ from
      one another in the shape of the female genital chamber sclerites, but not in the
      male genitalia. Oncometopia nigricans is almost identical in the genitalic
      characters of both sexes to O. hamiltoni sp. n., from which it is dissimilar
      externally, as confirmed by morphometric analysis, but is externally similar to
      O. orbona, from which it strongly differs in both the male and female genitalia.
      The rare intermediate forms from northern Florida and southern Georgia are
      interpreted as orbona x nigricans hybrids. Oncometopia clarior is treated as a
      complex of species which at present cannot be separated.

PMID- 27701351
TI  - Australnirvana, a new leafhopper genus of Nirvanini (Hemiptera: Cicadellidae:
      Evacanthinae) from Australia.
AB  - Australnirvana gen. n., based on Nirvana adelaideae Evans, 1938, from Australia
      is described and illustrated. The male and female genitalia of A. adelaideae
      (Evans), n. comb. are described and illustrated for the first time. The new genus
      is similar to the central African genus Afronirvana Evans in structure and
      coloration but differs in the male in lacking a ventral pygofer appendage and
      having the subgenital plate broad and oblique distally and lacking ventral
      macrosetae.

PMID- 27701352
TI  - Description of the first Oriental species of the ant genus Xymmer (Hymenoptera:
      Formicidae: Amblyoponinae).
AB  - The monotypic ant genus Xymmer Santschi, 1914 was established for X. muticus
      (Santschi, 1914) which has so far been known only from the West African
      subregion. The genus is easily distinguishable from the other amblyoponine genera
      by the anteromedian part of clypeus which is produced as a short rectangular
      lobe. Additional undescribed species had been found exclusively from Madagascar
      and Africa until recently. However, in March, 2015, a Xymmer colony was found in
      northern Central Vietnam. In the present paper Xymmer phungi sp. nov. is
      described as the first Oriental species of the genus. Although the worker of X.
      phungi is morphologically quite similar to that of X. muticus, the former is
      distinguishable from the latter by the following two characteristics of the
      worker: clypeal lobe 1/6 times as long as broad (vs. 1/3 times as long as broad
      in X. muticus); anterior margin of the lobe weakly concave (vs. almost straight
      in X. muticus). Xymmer phungi is well distinguished from Ethiopian Xymmer spp.
      for which 28S sequences are available from GenBank. Our observations suggest that
      the species feeds on geophilids (Chilopoda: Geophilomorpha). An updated key to
      Vietnamese genera of the subfamily Amblyoponinae is also provided.

PMID- 27701353
TI  - First record of Viannaiidae (Nematoda: Trichostrongylina) in fossorial rodents
      (Ctenomys spp.) from Central Argentina, with description of a new genus and
      species.
AB  - A new genus and species of Viannaiidae (Trichostrongylina, Heligmosomoidea),
      Ischilinema baldoi n. gen. et sp. is described parasitizing two species of tuco
      tucos, Ctenomys bergi and Ctenomys rosendopascuali (Rodentia, Hystricomorpha,
      Ctenomyidae) from Cordoba province, Central Argentina. No helminths were
      previously known from these two host species. The new genus is defined by the
      following characters: synlophe with 15 continuous ridges subequal in size,
      presence of left cuticular dilatation, a gap between ridges 1' and 2', bursa
      asymmetrical with dorsal ray hypertrophied and displaced to the right, and
      spicules not twisted. This is the first record of Viannaiidae from the
      Ctenomyidae, enlarging the host range of these parasites to five out of the 12
      extant families of caviomorphs.

PMID- 27701354
TI  - A new legskate, Sinobatis andamanensis (Rajiformes: Anacanthobatidae), from the
      Andaman Sea (northeastern Indian Ocean).
AB  - A new legskate, Sinobatis andamanensis sp. nov. is described from a small
      collection of specimens taken off Phuket (Thailand) during an exploratory survey
      of the Andaman Sea. It is the first species of Sinobatis and the only legskate
      known from the northern Indian Ocean. Sinobatis andamanensis sp. nov. has an
      especially long and narrowly pointed snout (preorbital length exceeding 23% TL)
      with an interorbital distance 7-9.5 in snout length (up to 6.7 in other Sinobatis
      species). Molecular data are unavailable for most members of the genus, but based
      on morphology it shares with S. caerulea bluish dorsal and ventral surfaces when
      fresh and a long ventral head (length 36-42% TL). As well as differing in several
      morphometric differences, Sinobatis andamanensis sp. nov. seems to be a much
      smaller legskate (males adult from 186 mm DW vs. still immature at 540 mm DW in
      S. caerulea). Sinobatis bulbicauda also has an expanded posterior tail, but S.
      andamanensis sp. nov. differs from that species in having a narrower disc (width
      at anterior orbit 3.7-4.9 vs. 5.2-7.8 times mouth width) and anterior pelvic-fin
      lobes (base width 2.7-5.0 vs. 1.7-3.2 in distance between pelvic-fin origins),
      and shorter and less-conical tooth cusps and fewer vertebrae (total centra 126
      133 vs. 148-171).

PMID- 27701355
TI  - A new species of Theloderma (Amphibia: Anura: Rhacophoridae) from Vietnam.
AB  - We describe a new species of Theloderma from northwestern Vietnam based on
      morphological differences and molecular divergence. Theloderma annae sp. nov. is
      distinguishable from its congeners on the basis of a combination of the following
      characters:  Size small, SVL 27.1-28.5 mm in males, 30.3-32.6 mm in females; head
      longer than wide;  vomerine teeth absent; snout long (SL/SVL 0.16-0.19); spines
      on upper eyelid absent;  tibiotarsal projection absent; dorsal skin smooth;
      dermal fringes on forearm and tarsus absent; dorsal surface grayish green; and
      throat and ventral surface of arms and thighs brown with white spots.

PMID- 27701356
TI  - Macropsini (Hemiptera: Cicadellidae) of Thailand, with description of two new
      species and three new country records.
AB  - The fauna of Thailand was previously known to include only a single species of
      Macropsini. Study of an extensive collection of recent Malaise trap samples from
      Thailand revealed the presence of five additional species of this leafhopper
      tribe, including two new species, Pediopsis thailandensis and Varicopsella
      odontoida spp. nov., described and illustrated herein; and three additional
      species, Macropsis hainanensis, P. rufoscutellata and V. elegans, previously
      recorded from neighboring countries. A key to genera and species of the
      Macropsini of Thailand is provided.

PMID- 27701357
TI  - A new species of Lilophaea Bechyne (Coleoptera, Chrysomelidae, Galerucinae) with
      a historical background and a checklist of the genus.
AB  - A new species of Lilophaea Bechyne (Luperina) from Southern Brazil, Lilophaea
      sulina sp. nov. is described and illustrated. The complexity behind the taxonomic
      history for Lilophaea in relation to two similar genera (Luperodes and
      Monolepta), is approached herein. After the description of L. sulina sp. nov., 19
      species of this genus are currently known, all Neotropical. An updated list of
      species of Lilophaea with their respective geographical distribution is provided.

PMID- 27701358
TI  - Description of two extraordinary new species of freshwater stingrays of the genus
      Potamotrygon endemic to the rio Tapajos basin, Brazil (Chondrichthyes:
      Potamotrygonidae), with notes on other Tapajos stingrays.
AB  - Stingrays from the rio Tapajos basin are reviewed based on material collected
      from its lower (i.e. from the mouth-lake to Itaituba), middle (from about the Sao
      Luiz rapids to the confluence of rios Juruena and Teles Pires), and upper (above
      the Juruena-Teles Pires confluence) segments. Two new species endemic to the mid
      and upper Tapajos, discovered long ago and common in the ornamental fish trade,
      are described. Potamotrygon albimaculata sp. nov. is part of the black stingray
      species group, and is diagnosed by its blackish brown dorsal disc color with
      numerous and generally evenly-spaced small whitish spots and faint ocelli,
      multiple rows of thorns broadly spread on dorsal and lateral tail, pelvic fins
      with broadly rounded apices, and two angular cartilages with the posterior far
      more slender but about as wide as the anterior angular. Potamotrygon jabuti sp.
      nov. is diagnosed by its marbled color pattern that undergoes remarkable change
      with growth as adults have elaborate designs of beige, golden to yellowish-orange
      spots or ocelli surrounded by a slender beige to golden mesh-like pattern, but
      neonates have simple, well-separated ocelli; this species also has a single to
      double row of tail thorns varying in their development, monognathic heterodonty
      with teeth of intermediate lateral rows of upper jaws larger and hexagonal, and
      two robust, more or less equally developed angular cartilages. Both species co
      occur in the relatively fast-flowing mid and upper Tapajos basin, but mostly
      occupy different areas of the river, with P. albimaculata sp. nov. more abundant
      in its central troughs but foraging at its margins, whereas P. jabuti sp. nov. is
      also present in smaller streams over rocky, sandy and leafy substrates. The
      Tapajos basin includes at least seven stingray species, but additional species
      probably also occur. Potamotrygon motoro, P. orbignyi, P. humerosa, Potamotrygon
      sp., and Paratrygon aiereba are present in the lower Tapajos mouth-lake, which
      may also include Plesiotrygon and Heliotrygon species. In addition to the new
      species described herein, P. orbignyi and Paratrygon cf. aiereba occur in the mid
      and upper Tapajos, along with another form (Potamotrygon cf. scobina) known only
      from the region of the Sao Luiz rapids. Therefore, three additional new species
      may be present in the Tapajos basin, which has one of the most diverse stingray
      assemblages known together with the rios Negro and Tocantins-Araguaia.

PMID- 27701359
TI  - Kirkegaardia (Polychaeta, Cirratulidae), new name for Monticellina Laubier,
      preoccupied in the Rhabdocoela, together with new records and descriptions of
      eight previously known and sixteen new species from the Atlantic, Pacific, and
      Southern Oceans.
AB  - A new name, Kirkegaardia, is proposed to replace Monticellina Laubier, 1961, a
      bitentaculate cirratulid polychaete genus, that is a junior homonym of the
      turbellarian Monticellina Westblad, 1953 (Platyhelminthes, Rhabdocoela). In
      addition, the opportunity is taken to complete a major revision of the genus
      including the redescription, revalidation, and separation of three species
      previously referred to synonymy with K. dorsobranchialis (Kirkegaard, 1959) and
      five other previously described species. In addition, 16 new species are
      described from the western North Atlantic, eastern and central Pacific, off
      western South America, and seas around Antarctica, bringing the total number of
      species in the genus to 38. Included are two new species of the unusual mud ball
      worms, first reported as Tharyx luticastellus Jumars, 1975, from southern
      California deep basins. A review of all 38 species reveals that three distinct
      species groups may be identified within the genus in addition to 5-6 species that
      may eventually be referred elsewhere. This review includes a discussion of the
      taxonomic characters and various newly defined character states that are found
      among species of Kirkegaardia. Several of these are unique among the
      Cirratulidae.

PMID- 27701360
TI  - The Neotropical cuckoo wasp genus Ipsiura Linsenmaier, 1959 (Hymenoptera:
      Chrysididae): revision of the species occurring in Brazil.
AB  - The species of the chrysidid genus Ipsiura are reviewed with emphasis on the taxa
      occurring in Brazil. In the present study 34 Ipsiura species are recognized,
      diagnosed, and illustrated. Two new species are described here: Ipsiura
      bohartiana Lucena sp. nov. and I. duckeana Lucena sp. nov., and two others are
      transferred from Neochrysis to Ipsiura: I. assecia (Linsenmaier, 1997), comb.
      nov. and I. guayanensis (Linsenmaier, 1997), comb. nov., increasing to 41 the
      total of valid species in the genus. New diagnoses and redescriptions are
      provided for 34 species based on study of their types. For the first time, a
      comparative and illustrated study of male genitalia is presented for the majority
      of Ipsiura species. Notes on types and depository collections, a revised key for
      identification of species along with illustrations of diagnostic features, as
      well as geographical distribution maps are also given.

PMID- 27701361
TI  - Cybaeus (Araneae: Cybaeidae): the Nearctic species of the Holarctic clade.
AB  - Species of North American Cybaeus L. Koch (Araneae: Dictynoidea: Cybaeidae) are
      classified in Holarctic and Californian clades. We review the Nearctic species of
      the Holarctic clade of these common moist-forest spiders. Twenty-one species
      grouped in informal tetricus (nine species) and angustiarum (twelve species)
      groups based on female genitalic characters are recognized, including four new
      species endemic to the western Nearctic: C. rothi Bennett sp. nov. (tetricus
      group) and C. charlesi Bennett sp. nov., C. harrietae Bennett sp. nov., and C.
      solanum Bennett sp. nov. (angustiarum group). Other Nearctic species in the
      tetricus group are C. cascadius Roth 1952, C. conservans Chamberlin & Ivie 1932,
      C. constrictus Chamberlin & Ivie 1942, C. eutypus Chamberlin & Ivie 1932, C.
      morosus Simon 1886, C. multnoma Chamberlin & Ivie 1942, C. paralypropriapus
      Bennett 2009, and C. waynei Bennett 2009. Other Nearctic species in the
      angustiarum group are C. bulbosus Exline 1935, C. giganteus Banks 1892, C.
      patritus Bishop & Crosby 1926, C. reticulatus Simon 1886, C. scopulatus
      Chamberlin & Ivie 1942, C. shoshoneus Chamberlin & Ivie 1932, C. signifer Simon
      1886, C. silicis Barrows 1919, and C. sinuosus Fox 1937. Approximately half of
      the Nearctic Cybaeus species of the Holarctic clade are relatively widely
      distributed and frequently encountered; the remaining species have restricted
      ranges. Descriptions, illustrations, and range maps are provided for all species
      and identification keys are also included.

PMID- 27701363
TI  - Influenza vaccine for 2016-2017.

PMID- 27701362
TI  - Taxonomy of Morellia Robineau-Desvoidy (Diptera: Muscidae): revision of the
      subgenera Morellia s. str. and Parapyrellia Townsend.
AB  - The subgenera Morellia Robineau-Desvoidy, 1830 and Parapyrellia Townsend, 1915 of
      Morellia (Diptera, Muscidae) are revised. Forty-two species of the subgenus
      Morellia (out of 50) and seven of the subgenus Parapyrellia (all species) are
      redescribed and illustrated, and 48 species are keyed (41 spp. of Morellia and 7
      spp. of Parapyrellia). Morellia (M.) cashmirana van Emden, 1965, originally
      described as a subspecies of M. (M.) hortorum (Fallen, 1817), is raised to
      species rank, stat. nov. Four species are transferred from the subgenus Morellia
      to the subgenus Parapyrellia (subgen. comb. nov.): M. dendropanacis Pamplona &
      Couri, 1995; M. lopesae Pamplona, 1986; M. roppai Pamplona, 1986 and M.
      semimarginata (Stein, 1918).

PMID- 27701364
TI  - Glycopyrrolate/formoterol (Bevespi Aerosphere) for COPD.

PMID- 27701365
TI  - In brief: Nitisinone (Orfadin) for hereditary tyrosinemia.

PMID- 27701366
TI  - Comparison of Intravenous Dexmedetomidine and Midazolam for Bispectral Index
      Guided Sedation During Spinal Anesthesia.
AB  - BACKGROUND Despite the high frequency of hypotension during spinal anesthesia
      with proper sedation, no previous report has compared the hemodynamic effects of
      dexmedetomidine and midazolam sedation during spinal anesthesia. We compared the
      effects of bispectral index (BIS)-guided intravenous sedation using midazolam or
      dexmedetomidine on hemodynamics and recovery profiles in patients who underwent
      spinal anesthesia. MATERIAL AND METHODS One hundred and sixteen adult patients
      were randomly assigned to receive either midazolam (midazolam group; n=58) or
      dexmedetomidine (dexmedetomidine group; n=58) during spinal anesthesia. Systolic,
      diastolic, and mean arterial pressures; heart rates; peripheral oxygen
      saturations; and bispectral index scores were recorded during surgery, and Ramsay
      sedation scores and postanesthesia care unit (PACU) stay were monitored. RESULTS
      Hypotension occurred more frequently in the midazolam group (P<0.001) and
      bradycardia occurred more frequently in the dexmedetomidine group (P<0.001). Mean
      Ramsay sedation score was significantly lower in the dexmedetomidine group after
      arrival in the PACU (P=0.025) and PACU stay was significantly longer in the
      dexmedetomidine group (P=0.003). CONCLUSIONS BIS-guided dexmedetomidine sedation
      can attenuate intraoperative hypotension, but induces more bradycardia, prolongs
      PACU stay, and delays recovery from sedation in patients during and after spinal
      anesthesia as compared with midazolam sedation.

PMID- 27701368
TI  - Transcranial direct current stimulation for improving idiopathic Parkinson's
      syndrome. An abridged version of a Cochrane review.
AB  - INTRODUCTION: Idiopathic Parkinson's Disease (IPD) is a neurodegenerative
      disorder. The severity of disability usually increases with disease duration and
      affects patients' impairment, disability and health-related quality of life. A
      possible adjunct to improve outcomes in patients with IPD might be transcranial
      direct current stimulation (tDCS) to modulate cortical excitability and hence
      improving outcomes in people with IPD. EVIDENCE ACQUISITION: Until February 2016
      we searched the following databases: the Cochrane Central Register of Controlled
      Trials (CENTRAL; the Cochrane Library; 2016, Issue 2), MEDLINE, EMBASE, CINAHL,
      AMED, Science Citation Index, the Physiotherapy Evidence Database (PEDro),
      Rehabdata, and Inspec and handsearched conference proceedings, and contacted
      authors and equipment manufacturers. We included only randomized controlled
      trials (RCTs) and randomized controlled crossover trials comparing tDCS versus
      control interventions in adults with IPD. EVIDENCE SYNTHESIS: Two authors
      independently extracted data and assessed trial quality. We included six trials
      with 137 participants. There was no effect of tDCS compared to sham tDCS in our
      primary outcome measure, impairment, as measured by the proportional change of
      the Unified Parkinson's Disease Rating Scale (UPDRS) (mean difference (MD) 
      7.10%, 95% confidence interval (CI) -19.18 to 4.97; P=0.25). There was evidence
      of an effect on UPDRS part III motor subsection score at the end of the
      intervention period (MD -14.43%, 95% CI -24.68 to -4.18; P=0.006). There was no
      evidence of an effect regarding the reduction in off time and on time with
      dyskinesia (MD 0.10 hours, 95% CI -0.14 to 0.34; P=0.41; and MD 0.00 hours, 95%
      CI -0.12 to 0.12; P=1, respectively). There was no evidence of an effect for gait
      speed, health related quality of life and safety/acceptability, measured by
      dropouts and adverse events (including death). CONCLUSIONS: There is insufficient
      evidence to determine the effects of tDCS in reducing off time and on time with
      dyskinesia and for improving health-related quality of life, disability and
      impairment in patients with IPD.

PMID- 27701367
TI  - Current management of diabetic patients with kidney disease: a renal-cardio
      endocrine perspective.
AB  - Diabetic kidney disease (DKD) is one of the most frequent and dangerous
      complications of diabetes mellitus type 2, affecting about one-third of the
      patients. DKD results in increased hospitalizations and mortality rates,
      especially due to cardiovascular complications. This high burden of kidney
      disease is mainly due to the increasing complexity of in- outpatient care for
      patients with DM. There is a strikingly complex interaction of kidney dysfunction
      with many aspects of diabetes care, such as redefinition of targets of treatment,
      interactions of traditional and non-traditional risk factors, and pharmacological
      issues related to pharmacokinetic and side effects of drugs. Particularly when
      not carefully managed, DKD increases the demand for renal replacement therapies,
      such as dialysis and kidney transplants. The combined economic and social costs
      of this disease are high and of concern to the world's health systems. The main
      objective of this review is to provide insight into the recommendations for the
      evaluation and stratification of DKD and how the presence of kidney disease
      changes the optimal management of diabetic patients from an integrated renal
      cardio-endocrine perspective.

PMID- 27701370
TI  - Intra-arterial injection of iloprost reduces the risk of early recoil after
      balloon angioplasty of below-the-knee vessels in patients with critical limb
      ischemia.
AB  - BACKGROUND: Previous studies demonstrated that early recoil is frequently
      observed in patients undergoing balloon angioplasty. The aim of this study was to
      evaluate the impact of intra-arterial administration of iloprost (Endoprost(r),
      Italfarmaco S.p.A., Milan, Italy) on early elastic recoil after balloon
      angioplasty of below-the-knee (BTK) vessels in patients with critical limb
      ischemia (CLI). METHODS: Between January 2015 and December 2015 32 patients with
      CLI underwent balloon angioplasty of at least one BTK vessel followed by intra
      arterial administration of iloprost. Early elastic recoil was defined as residual
      lumen compromise >10%. Early elastic recoil was determined on the basis of
      minimal lumen diameter (MLD) measurements at baseline (MLDbaseline), immediately
      after BTK balloon angioplasty (MLDpostdilation), and 15 minutes thereafter
      (MLD15min). RESULTS: Patients were predominantly female (18/32, 56.2%) with a
      mean age of 79.6 years (range 68- 87). Most of the patients were diabetics
      (25/32, 78.1%). An occlusion was present in 24 cases (75%). Mean BTK lesion
      length was 144.1 mm (range 22-320). Mean MLD measurements were 0.1 mm (range 0
      0.5; MLDbaseline), 2.5 mm (range 1.9-3; MLDpostdilation), and 1.9 mm (range 0.7
      3; MLD15min). Early elastic recoil was recorded in 14 patients (43.8%). The mean
      percentage of elastic recoil after 15 minutes was 21.4%. CONCLUSIONS: In our
      experience intra-arterial administration of iloprost reduces the risk of early
      elastic recoil after balloon angioplasty of BTK vessels in patients with CLI.
      Further analyses with larger population studies and randomized trials are needed
      to validate this therapeutic option.

PMID- 27701371
TI  - Burnout syndrome and wellbeing in anesthesiologists: the importance of emotion
      regulation strategies.
AB  - Anesthesiologists face stressful working conditions that can culminate in burnout
      syndrome. Despite various studies and protective measures which have attempted to
      prevent this situation, burnout continues to be a problem within the profession,
      impacting negatively on physicians' lives and their performance. In this review
      article mechanisms and consequences of burnout are described in addition to
      individual strategies for stress management and burnout reduction with potential
      impact on health care quality and wellbeing in anesthesiologists. Organizational
      strategies appear to have an important role in burnout reduction but need to be
      used in conjunction with individual programs. The latter are essential to both
      reducing stress and burnout in anesthesiologists and improving happiness and
      wellbeing. New measures of emotion regulation strategies such as mindfulness,
      self-compassion, resilience and empathy promotion have been shown to be
      approaches with substantial supporting evidence for reducing burnout and
      improving stress management. The evaluation and implementation of these self
      regulatory competencies is a challenge. Further research is necessary to identify
      which programs will best suit the needs of anesthesiologists and to measure their
      effects on patient care and health care system quality.

PMID- 27701372
TI  - Can pre-procedure neuroaxial ultrasound improve the identification of the
      potential epidural space when compared with anatomical landmarks? A prospective
      randomized study.
AB  - BACKGROUND: Regional epidural analgesia is considered the gold standard for pain
      treatment in labor. However, epidural catheter placement may be a challenging
      procedure because of the difficulty in the palpation of anatomical landmarks,
      particularly in pregnant women. Pre-procedural neuroaxial ultrasound may
      facilitate the procedure. METHODS: A prospective randomized controlled study was
      conducted in a labor ward. Two groups of women undergoing epidural analgesia were
      randomized: Group A (N.=28), which was subjected to the loss of resistance
      technique, and Group B (N.=30) which was subjected to an ultrasound (US)-assisted
      procedure. The real depth of epidural space was calculated in both groups by
      measuring the needle skin-to-tip distance, while the US depth was measured only
      in Group B. RESULTS: The mean number of attempts in group A (3.43+/-3.8) was
      significantly higher than in Group B (1.70+/-0.87, P=0.019). Analysis of data
      from Group B revealed a strong positive correlation between the epidural real
      depth and US depth (r=0.88, P<0.0001). CONCLUSIONS: The US-assisted technique for
      epidural catheter placement for labor analgesia is safe, effective, easy to
      perform, and is a valuable aid to improve the identification of the epidural
      space compared with the palpation of anatomical landmarks and the loss of
      resistance technique. Pre-puncture ultrasound assessment shows the exact location
      of the intervertebral space, the optimal point of insertion and the tilt angle of
      the needle, the depth of the epidural space and any anatomical abnormalities of
      the spine, thereby increasing the success rate and reducing procedural
      complications of the blind approach.

PMID- 27701369
TI  - Transaxillary versus transaortic approach for transcatheter aortic valve
      implantation with CoreValve Revalving System: insights from multicenter
      experience.
AB  - BACKGROUND: About one-third of candidates for transcatheter aortic valve
      implantation (TAVI) suffer from severe peripheral artery disease, making the
      routine femoral approach difficult or impossible. The aim was to compare the
      transaxillary (TAx) and the transaortic (TAo) route for TAVI with Medtronic
      CoreValve Revalving System (CRS). METHODS: Out of 1049 consecutive TAVI with 18F
      CRS, 242 (23%) were treated in 4 high-volume Italian Centre through TAx (61%) and
      TAo (39%). RESULTS: The devices success was similar (P=0.16) with a trend to a
      lower incidence of significant paravalvular leak (6% vs. 14%, P=0.07) and a
      significant reduction of permanent pacemaker (PPM) implantation (13% vs. 34%,
      P=0.017) in the TAo. However, this route showed a higher incidence of acute
      kidney injury (P=0.016) and a longer hospital stay after the index procedure
      (days 10 [8-14] vs. 8 [7-12], P=0.001). By a multivariate analysis the vascular
      access is an independent predictor for a longer hospital stay (TAo route;
      OR=0.37, 95% CI: 0.18-0.75; P=0.006) and for PPM implantation (TAx route; OR=3.7,
      95% CI: 1.2-10.8; P=0.017). CONCLUSIONS: Although the higher clinical risk
      profile of transaortic population, the TAo approach showed an equally high device
      success with similar 30-day safety and 1year efficacy, compared to TAx route.
      However, due to non-procedure-specific complications post-TAo TAVI, this route
      requires a specialized postoperative care and the treatment of patients in highly
      specialized and experienced centers.

PMID- 27701373
TI  - The ultrasound-guided parasternal block: a novel approach for anesthesia and
      analgesia in breast cancer surgery.

PMID- 27701374
TI  - Arterial catheters' dysfunction according to insertion site: an observational
      study.

PMID- 27701375
TI  - Intraoperative radiotherapy in gastric and esophageal cancer: meta-analysis of
      long-term outcomes and complications.
AB  - INTRODUCTION: The treatment effects of intraoperative radiotherapy (IORT) for
      gastric and esophageal cancer remain uncertain. We therefore performed meta
      analyses to investigate whether IORT was associated with more favorable oncologic
      outcomes when compared to non-IORT for patients who have gastric or esophageal
      cancer. EVIDENCE ACQUISITION: PubMed, Embase, and the references of relevant
      studies were systematically searched up to March 2016. Outcomes were analyzed
      with fixed-effect or random-effect models, and the meta-analysis was completed
      with odds ratio (OR), hazards ratio (HR), and 95% confidence intervals (CI) as
      effect values. EVIDENCE SYNTHESIS: Eleven studies were included, nine for gastric
      cancer and two for esophageal cancer. The studies included 1581 patients, 570 in
      the IORT group and 1011 in the control group. There was no significant difference
      in overall survival (OS) between the IORT group and control group (HR=0.91, 95%
      CI: 0.73-1.13; P=0.38). Two subgroups based on cancer type also had the similar
      results (gastric group: HR=0.98, 95% CI: 0.78-1.24, P=0.87; esophagus group:
      HR=0.63, 95% CI: 0.37-1.05, P=0.08). Besides, IORT showed favorable effects for
      patients with cancer in stage II and stage III and had the advantage of loco
      regional control. Regarding the complications, the occurrence rate had no
      significant difference between the IORT group and control group (OR=1.15; 95% CI:
      0.77-1.72; P=0.50). CONCLUSIONS: According to our meta-analysis, IORT did not
      extend the OS in gastric cancer and esophageal cancer patients, but had a
      favorable effect for specific stage patients to show loco-regional control, and
      did not increase the risk of complications.

PMID- 27701376
TI  - Predictors of rapid disease progression in autosomal dominant polycystic kidney
      disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common
      genetic diseases with a reported prevalence of 1:400 to 1:1000. Since the intact
      kidneys can compensate for the loss of glomerular filtration in ADPKD patients,
      renal insufficiency usually remains undetected until almost the fourth decade of
      life. Hereafter, reliable diagnostic and prognostic biomarkers to identify ADPKD
      progression are urgently needed. Several studies and systematic reviews tried to
      identify markers or predictors of rapid disease progression of ADPKD. The aim of
      this study is to review predictors of rapid disease progression of ADPKD that can
      be useful to the clinician. We will describe several factors associated with
      rapid progression of ADPKD derived from retrospective or cross-sectional studies,
      suggesting the best and most useful predictors that may help to patients
      management in clinical practice. We will attempt to identify the most useful
      predictors of rapid disease progression of ADPKD: established TKV growth rate >5%
      per year, annual estimated glomerular filtration rate decline >5 mL/min/1.73 m2,
      truncating PKD1 mutations and elevated plasma copeptin level. The combination of
      several factors that can predict the rapid ADPKD progression is more accurate
      than a single-marker strategy. The "PRO-PKD" risk scoring system combined with
      TKV, can be useful in order to evaluate the ADPKD patients and they appear to be
      appropriate predictors of progression disease. Moreover levels of copeptin and
      some urinary markers can be matched to these factors for improved patient
      assessment in rapid progression.

PMID- 27701377
TI  - Global cooling as a driver of diversification in a major marine clade.
AB  - Climate is a strong driver of global diversity and will become increasingly
      important as human influences drive temperature changes at unprecedented rates.
      Here we investigate diversification and speciation trends within a diverse group
      of aquatic crustaceans, the Anomura. We use a phylogenetic framework to
      demonstrate that speciation rate is correlated with global cooling across the
      entire tree, in contrast to previous studies. Additionally, we find that marine
      clades continue to show evidence of increased speciation rates with cooler global
      temperatures, while the single freshwater clade shows the opposite trend with
      speciation rates positively correlated to global warming. Our findings suggest
      that both global cooling and warming lead to diversification and that habitat
      plays a role in the responses of species to climate change. These results have
      important implications for our understanding of how extant biota respond to
      ongoing climate change and are of particular importance for conservation planning
      of marine ecosystems.

PMID- 27701378
TI  - Donor and host photoreceptors engage in material transfer following
      transplantation of post-mitotic photoreceptor precursors.
AB  - Photoreceptor replacement by transplantation is proposed as a treatment for
      blindness. Transplantation of healthy photoreceptor precursor cells into diseased
      murine eyes leads to the presence of functional photoreceptors within host
      retinae that express an array of donor-specific proteins. The resulting
      improvement in visual function was understood to be due to donor cells
      integrating within host retinae. Here, however, we show that while integration
      occurs the majority of donor-reporter-labelled cells in the host arises as a
      result of material transfer between donor and host photoreceptors. Material
      transfer does not involve permanent donor-host nuclear or cell-cell fusion, or
      the uptake of free protein or nucleic acid from the extracellular environment.
      Instead, RNA and/or protein are exchanged between donor and host cells in vivo.
      These data require a re-evaluation of the mechanisms underlying rescue by
      photoreceptor transplantation and raise the possibility of material transfer as a
      strategy for the treatment of retinal disorders.

PMID- 27701379
TI  - Hypoplastic left heart syndrome: from comfort care to long-term survival.
AB  - The management of hypoplastic left heart syndrome (HLHS) has changed
      substantially over the past four decades. In the 1970s, children with HLHS could
      only be provided with supportive care. As a result, most of these unfortunate
      children died within the neonatal period. The advent of the Norwood procedure in
      the early 1980s has changed the prognosis for these children, and the majority
      now undergoing a series of three surgical stages that can support survival beyond
      the neonatal period and into early adulthood. This review will focus on the
      Norwood procedure and the other important innovations of the last half century
      that have improved our outlook toward children born with HLHS.

PMID- 27701381
TI  - Retinal transplantation of photoreceptors results in donor-host cytoplasmic
      exchange.
AB  - Pre-clinical studies provided evidence for successful photoreceptor cell
      replacement therapy. Migration and integration of donor photoreceptors into the
      retina has been proposed as the underlying mechanism for restored visual
      function. Here we reveal that donor photoreceptors do not structurally integrate
      into the retinal tissue but instead reside between the photoreceptor layer and
      the retinal pigment epithelium, the so-called sub-retinal space, and exchange
      intracellular material with host photoreceptors. By combining single-cell
      analysis, Cre/lox technology and independent labelling of the cytoplasm and
      nucleus, we reliably track allogeneic transplants demonstrating cellular content
      transfer between graft and host photoreceptors without nuclear translocation. Our
      results contradict the common view that transplanted photoreceptors migrate and
      integrate into the photoreceptor layer of recipients and therefore imply a re
      interpretation of previous photoreceptor transplantation studies. Furthermore,
      the observed interaction of donor with host photoreceptors may represent an
      unexpected mechanism for the treatment of blinding diseases in future cell
      therapy approaches.

PMID- 27701380
TI  - Identification of Helicobacter pylori and the evolution of an efficacious
      childhood vaccine to protect against gastritis and peptic ulcer disease.
AB  - Establishment of Helicobacter pylori infection as an etiologic agent of peptic
      ulcer disease and other gastric pathologies marked a revolution in
      gastroenterology which spurred an enormous interest in gastric physiology and
      immunology research. The association was soon also demonstrated in children as
      well. Application of antimicrobial therapies have proven remarkably efficacious
      in eradicating H. pylori and curing pediatric patients of duodenal ulcers as well
      as gastritis, negating a lifetime of ineffective therapy and life-threatening
      disease. Countries with high H. pylori prevalence and where H. pylori associated
      gastric cancer remains a primary cause of death due to cancer however would
      benefit from childhood vaccination. Studies in rodents and humans utilizing oral
      vaccination with bacterial exotoxin adjuvants demonstrated potential for limiting
      H. pylori colonization in the stomach. Almost 25 y of vaccine research recently
      culminated in a phase III clinical trial of over 4,000 children aged 6-15 y old
      to test an oral vaccine consisting of the H. pylori urease B subunit genetically
      fused to the E. coli heat labile toxin. Vaccination was demonstrated to have an
      efficacy of over 70%. Vaccination may now serve as an effective strategy to
      significantly reduce H. pylori associated disease in children throughout the
      world.

PMID- 27701383
TI  - Risk of hospitalisation and death due to bone fractures after breast cancer: a
      registry-based cohort study.
AB  - BACKGROUND: Bone fractures may have an impact on prognosis of breast cancer. The
      long-term risks of bone fracture in breast cancer patients have not been
      thoroughly studied. METHODS: Poisson regression was used to investigate the
      incidence of hospitalisation due to bone fracture comparing women with and
      without breast cancer based on Swedish National registers. Cox regression was
      used to investigate the risk of being hospitalised with bone fracture, and
      subsequent risk of death, in a regional cohort of breast cancer patients.
      RESULTS: For breast cancer patients, the 5-year risk of bone fracture
      hospitalisation was 4.8% and the 30-day risk of death following a bone fracture
      hospitalisation was 2.0%. Compared with the general population, breast cancer
      patients had incidence rate ratios of 1.25 (95% CI: 1.23-1.28) and 1.18 (95% CI:
      1.14-1.22) for hospitalisation due to any bone fracture and hip fracture,
      respectively. These ratios remained significantly increased for 10 years.
      Comorbidities (Charlson Comorbidity Index ?1) were associated with the risk of
      being hospitalised with bone fracture. Women taking aromatase inhibitors were at
      an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98
      2.22). Breast cancer patients hospitalised for a bone fracture showed a higher
      risk of death (HR=1.83; 95% CI: 1.50-2.22) compared with those without bone
      fracture. CONCLUSIONS: Women with a previous breast cancer diagnosis are at an
      increased risk of hospitalisation due to a bone fracture, particularly if they
      have other comorbidities.

PMID- 27701382
TI  - Fhf2 gene deletion causes temperature-sensitive cardiac conduction failure.
AB  - Fever is a highly conserved systemic response to infection dating back over 600
      million years. Although conferring a survival benefit, fever can negatively
      impact the function of excitable tissues, such as the heart, producing cardiac
      arrhythmias. Here we show that mice lacking fibroblast growth factor homologous
      factor 2 (FHF2) have normal cardiac rhythm at baseline, but increasing core body
      temperature by as little as 3  degrees C causes coved-type ST elevations and
      progressive conduction failure that is fully reversible upon return to
      normothermia. FHF2-deficient cardiomyocytes generate action potentials upon
      current injection at 25  degrees C but are unexcitable at 40  degrees C. The
      absence of FHF2 accelerates the rate of closed-state and open-state sodium
      channel inactivation, which synergizes with temperature-dependent enhancement of
      inactivation rate to severely suppress cardiac sodium currents at elevated
      temperatures. Our experimental and computational results identify an essential
      role for FHF2 in dictating myocardial excitability and conduction that safeguards
      against temperature-sensitive conduction failure.

PMID- 27701384
TI  - Reproductive and hormonal factors in relation to survival and platinum resistance
      among ovarian cancer cases.
AB  - BACKGROUND: Ovarian cancer survival is poor, particularly for platinum-resistant
      cases. The previous literature on pre-diagnostic reproductive factors and ovarian
      cancer survival has been mixed. Therefore, we evaluated pre-diagnostic
      reproductive and hormonal factors with overall survival and, additionally,
      platinum-chemotherapy resistance. METHODS: We followed 1649 invasive epithelial
      ovarian cancer cases who were enrolled between 1992 and 2008 for overall
      mortality within the New England Case-Control Study and abstracted chemotherapy
      data on a subset (n=449). We assessed pre-diagnostic reproductive and hormonal
      factors during in-person interviews. We calculated hazard ratios (HRs) using Cox
      proportional hazards models. RESULTS: We observed 911 all-cause deaths among 1649
      ovarian cancer cases. Self-reported endometriosis and longer duration of hormone
      therapy use were associated with improved survival (HR: 0.72; 95% confidence
      interval (CI): 0.54-0.94 and HR, ?5 years vs never: 0.70; 95% CI: 0.55-0.90,
      respectively). Older age at menopause and menarche were associated with worse
      survival (HR, ?50 vs >50 years: 1.23; 95% CI: 1.03-1.46 and HR, 13 vs <13 years:
      1.24; 95% CI: 1.06-1.44, respectively). We observed no association between oral
      contraceptive use, parity and tubal ligation, and overall survival. No
      significant associations were observed for any of the reproductive and hormonal
      factors and platinum resistance. CONCLUSIONS: These results suggest that pre
      diagnostic exposures such as endometriosis and HT use may influence overall
      survival among ovarian cancer patients.

PMID- 27701385
TI  - A prognostic profile of hypoxia-induced genes for localised high-grade soft
      tissue sarcoma.
AB  - BACKGROUND: For decades, tumour hypoxia has been pursued as a cancer treatment
      target. However, prognostic and predictive biomarkers are essential for the use
      of this target in the clinic. This study investigates the prognostic value of a
      hypoxia-induced gene profile in localised soft tissue sarcoma (STS). METHODS: The
      hypoxia-induced gene quantification was performed by real-time quantitative PCR
      (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene
      expression cut-points were determined in a test cohort of 55 STS patients and
      used to allocate each patient into a more or a less hypoxic group. The cut-points
      found in the test cohort were applied to a cohort of 77 STS patients for
      validation. RESULTS: For patients with localised high-grade STS treated with
      surgery with or without postoperative radiation therapy, the prognostic value of
      the hypoxia-induced gene profile was proved in the test cohort and confirmed in
      the validation cohort. After adjustment for confounders, the hazard ratio (HR)
      was 3.2 (95% CI: 1.5; 7.0) for patients with more hypoxic tumours compared with
      patients with less hypoxic tumours regarding disease-specific survival. Moreover,
      for the development of metastatic disease, the HR was 2.61 (95% CI: 1.27; 5.33).
      CONCLUSIONS: The hypoxia-induced gene profile is a validated independent
      prognostic marker that may help identify STS patients needing more aggressive or
      different adjuvant treatment.

PMID- 27701386
TI  - Reproductive history and risk of colorectal adenocarcinoma in parous women: a
      Nordic population-based case-control study.
AB  - BACKGROUND: Data are conflicting regarding the role of endogenous sex hormones in
      colorectal carcinogenesis. In this large population-based study, we pooled data
      from birth and cancer registries in four Nordic countries, to evaluate the risk
      of colorectal adenocarcinoma in relation to women's reproductive history.
      METHODS: We conducted a population-based case-control study among women
      registered in Nordic birth registries. The study included colorectal
      adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during
      1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220
      246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were
      derived from conditional logistic regression models. We had limited information
      available on possible confounders. RESULTS: We found no evidence for associations
      between colorectal adenocarcinoma and parity, age at first and last birth, and
      time since first and last birth. The risk estimates were also close to unity for
      specific cancer subsites (proximal and distal colon and rectum). As well, when
      the analyses were stratified on menopausal status, parity, and mother's year of
      birth, no indication of associations was found. CONCLUSIONS: In this large,
      Nordic population-based study, no evidence for associations was found between
      women's reproductive history and colorectal adenocarcinoma in parous women.

PMID- 27701387
TI  - Factors associated with recurrence and survival length following relapse in
      patients with neuroblastoma.
AB  - BACKGROUND: Despite therapeutic advances, survival following relapse for
      neuroblastoma patients remains poor. We investigated clinical and biological
      factors associated with length of progression-free and overall survival following
      relapse in UK neuroblastoma patients. METHODS: All cases of relapsed
      neuroblastoma, diagnosed during 1990-2010, were identified from four Paediatric
      Oncology principal treatment centres. Kaplan-Meier and Cox regression analyses
      were used to calculate post-relapse overall survival (PROS), post-relapse
      progression-free survival (PRPFS) between relapse and further progression, and to
      investigate influencing factors. RESULTS: One hundred eighty-nine cases were
      identified from case notes, 159 (84.0%) high risk and 17 (9.0%), unresectable,
      MYCN non-amplified (non-MNA) intermediate risk (IR). For high-risk patients
      diagnosed >2000, median PROS was 8.4 months (interquartile range (IQR)=3.0-17.4)
      and median PRPFS was 4.7 months (IQR=2.1-7.1). For IR, unresectable non-MNA
      patients, median PROS was 11.8 months (IQR 9.0-51.6) and 5-year PROS was 24% (95%
      CI 7-45%). MYCN amplified (MNA) disease and bone marrow metastases at diagnosis
      were independently associated with worse PROS for high-risk cases. Eighty percent
      of high-risk relapses occurred within 2 years of diagnosis compared with 50% of
      unresectable non-MNA IR disease. CONCLUSIONS: Patients with relapsed HR
      neuroblastomas should be treatment stratified according to MYCN status and PRPFS
      should be the primary endpoint in early phase clinical trials. The failure to
      salvage the majority of IR neuroblastoma is concerning, supporting investigation
      of intensification of upfront treatment regimens in this group to determine
      whether their use would diminish likelihood of relapse.

PMID- 27701388
TI  - Patterns of response to anti-PD-1 treatment: an exploratory comparison of four
      radiological response criteria and associations with overall survival in
      metastatic melanoma patients.
AB  - BACKGROUND: Radiological assessment of response to checkpoint inhibitors remains
      imperfect. We evaluated individual lesion and inter-patient response by response
      evaluation (RECIST) 1.1, immune-related response criteria (irRC), CHOI and
      modified CHOI (mCHOI) and correlated response with overall survival (OS).
      METHODS: Thirty-seven patients with 567 measurable lesions treated with
      pembrolizumab in the Keynote 001 trial were studied. Association of response with
      OS was determined. RESULTS: Response varied according to site; lung lesions had
      the highest rate of complete response (69 out of 163 (42%) vs other sites 71 out
      of 404 (18%), P<0.0001). Delayed response post first scan was seen in 2 out of 37
      (5%) deemed progressive (PD) by RECIST and 2 out of 14 (14%) deemed PD by irRC.
      Modified CHOI criteria showed response of 38% (14 out of 37). Change in tumour
      size and density on first follow-up assessment was associated with OS with each
      1000 mm2 increase in tumour size from baseline increasing the hazard of dying by
      25.9% (HR=1.259, (95% CI=1.116-1.420), P=0.0002). Similarly, each 20HU increase
      in density increased the HR by 15% (HR=1.15, (95% CI 1.045-1.260), P=0.004).
      Response defined by any criteria had superior OS (CHOI P=0.0084; mCHOI P=0.0183;
      irRC P<0.0001 and RECIST P=0.0003). CONCLUSIONS: Response by any criterion was
      prognostic. Novel patterns of response and changes on treatment in tumour density
      suggest complex anti-tumour responses to immunotherapy.

PMID- 27701391
TI  - Epigenetics: Imprinting evolution in Arabidopsis.

PMID- 27701392
TI  - Plant genomics: African origins of 'black rice'.

PMID- 27701393
TI  - Enlivening the barren leaves.

PMID- 27701389
TI  - Intermediate-stage hepatocellular carcinoma treated with hepatic resection: the
      NSP score as an aid to decision-making.
AB  - BACKGROUND: The subgroups of patients with intermediate-stage (BCLC-B)
      hepatocellular carcinoma (HCC) who would truly benefit from hepatic resection
      (HR) are unknown. An objective point score was established to guide the selection
      of these patients for HR. METHODS: In all, 255 consecutive patients with
      intermediate-stage HCC treated with HR were evaluated retrospectively and
      included in this study (the training cohort). The variables on overall survival
      (OS, log-rank test) were investigated and a point score (the NSP score) was
      developed by using a Cox-regression model and validated in an independent
      external cohort from another institution (n=169). RESULTS: The NSP score
      differentiated two groups of patients (?1, >1 point) with distinct prognoses
      (median OS, 61.3 vs 19.3 months; P<0.001). A high NSP score was associated with
      increased major adverse events after HR (5.6 vs 13.8%, P=0.027). Its predictive
      accuracy as determined by the area under the receiver operating characteristic
      curve (AUC) at 1, 3, and 5 years (AUCs 0.688, 0.739, and 0.732) was greater than
      the other six staging systems for HCC (0.513-0.677). The findings were supported
      by the validation cohort. CONCLUSIONS: The NSP scoring system is more accurate in
      selecting patients with intermediate-stage HCC for HR.

PMID- 27701395
TI  - Plant breeding: Effective use of genetic diversity.

PMID- 27701398
TI  - Divergent effects of central melanocortin signalling on fat and sucrose
      preference in humans.
AB  - Melanocortin-4-receptor (MC4R)-expressing neurons modulate food intake and
      preference in rodents but their role in human food preference is unknown. Here we
      show that compared with lean and weight-matched controls, MC4R deficient
      individuals exhibited a markedly increased preference for high fat, but a
      significantly reduced preference for high sucrose food. These effects mirror
      those in Mc4r null rodents and provide evidence for a central molecular circuit
      influencing human macronutrient preference.

PMID- 27701399
TI  - An Exon-Specific U1snRNA Induces a Robust Factor IX Activity in Mice Expressing
      Multiple Human FIX Splicing Mutants.
AB  - In cellular models we have demonstrated that a unique U1snRNA targeting an
      intronic region downstream of a defective exon (Exon-specific U1snRNA, ExSpeU1)
      can rescue multiple exon-skipping mutations, a relevant cause of genetic disease.
      Here, we explored in mice the ExSpeU1 U1fix9 toward two model Hemophilia B
      causing mutations at the 5' (c.519A > G) or 3' (c.392-8T > G) splice sites of F9
      exon 5. Hydrodynamic injection of wt-BALB/C mice with plasmids expressing the wt
      and mutant (hFIX-2G5'ss and hFIX-8G3'ss) splicing-competent human factor IX
      (hFIX) cassettes resulted in the expression of hFIX transcripts lacking exon 5 in
      liver, and in low plasma levels of inactive hFIX. Coinjection of U1fix9, but not
      of U1wt, restored exon inclusion of variants and in the intrinsically weak FIXwt
      context. This resulted in appreciable circulating hFIX levels (mean +/- SD; hFIX
      2G5'ss, 1.0 +/- 0.5 ug/ml; hFIX-8G3'ss, 1.2 +/- 0.3 ug/ml; and hFIXwt, 1.9 +/-
      0.6 ug/ml), leading to a striking shortening (from ~100 seconds of untreated mice
      to ~80 seconds) of FIX-dependent coagulation times, indicating a hFIX with normal
      specific activity. This is the first proof-of-concept in vivo that a unique
      ExSpeU1 can efficiently rescue gene expression impaired by distinct exon-skipping
      variants, which extends the applicability of ExSpeU1s to panels of mutations and
      thus cohort of patients.

PMID- 27701400
TI  - Tissue-specific Calibration of Real-time PCR Facilitates Absolute Quantification
      of Plasmid DNA in Biodistribution Studies.
AB  - Analysis of the tissue distribution of plasmid DNA after administration of
      nonviral gene delivery systems is best accomplished using quantitative real-time
      polymerase chain reaction (qPCR), although published strategies do not allow
      determination of the absolute mass of plasmid delivered to different tissues.
      Generally, data is expressed as the mass of plasmid relative to the mass of
      genomic DNA (gDNA) in the sample. This strategy is adequate for comparisons of
      efficiency of delivery to a single site but it does not allow direct comparison
      of delivery to multiple tissues, as the mass of gDNA extracted per unit mass of
      each tissue is different. We show here that by constructing qPCR standard curves
      for each tissue it is possible to determine the dose of intact plasmid remaining
      in each tissue, which is a more useful parameter when comparing the fates of
      different formulations of DNA. We exemplify the use of this tissue-specific qPCR
      method by comparing the delivery of naked DNA, cationic DNA complexes, and
      neutral PEGylated DNA complexes after intramuscular injection. Generally, larger
      masses of intact plasmid were present 24 hours after injection of DNA complexes,
      and neutral complexes resulted in delivery of a larger mass of intact plasmid to
      the spleen.

PMID- 27701401
TI  - The Functionality of Minimal PiggyBac Transposons in Mammalian Cells.
AB  - Minimal piggyBac vectors are a modified single-plasmid version of the classical
      piggyBac delivery system that can be used for stable transgene integration. These
      vectors have a truncated terminal domain in the delivery cassette and thus,
      integrate significantly less flanking transposon DNA into host cell chromatin
      than classical piggyBac vectors. Herein, we test various characteristics of this
      modified transposon. The integration efficiency of minimal piggyBac vectors was
      inversely related to the size of both the transposon and the entire plasmid, but
      inserts as large as 15 kb were efficiently integrated. Open and super-coiled
      vectors demonstrated the same integration efficiency while DNA methylation
      decreased the integration efficiency and silenced the expression of previously
      integrated sequences in some cell types. Importantly, the incidence of plasmid
      backbone integration was not increased above that seen in nontransposon control
      vectors. In BALB/c mice, we demonstrated prolonged expression of two transgenes
      (intracellular mCherry and secretable Gaussia luciferase) when delivered by the
      minimal piggyBac that resulted in a more sustained antibody production against
      the immunogenic luciferase than when delivered by a transient (nontransposon)
      vector plasmid. We conclude that minimal piggyBac vectors are an effective
      alternative to other integrative systems for stable DNA delivery in vitro and in
      vivo.

PMID- 27701402
TI  - Percentile reference values for anthropometric body composition indices in
      European children from the IDEFICS study.

PMID- 27701403
TI  - Genome-scale high-resolution mapping of activating and repressive nucleotides in
      regulatory regions.
AB  - Massively parallel reporter assays (MPRAs) enable nucleotide-resolution
      dissection of transcriptional regulatory regions, such as enhancers, but only few
      regions at a time. Here we present a combined experimental and computational
      approach, Systematic high-resolution activation and repression profiling with
      reporter tiling using MPRA (Sharpr-MPRA), that allows high-resolution analysis of
      thousands of regions simultaneously. Sharpr-MPRA combines dense tiling of
      overlapping MPRA constructs with a probabilistic graphical model to recognize
      functional regulatory nucleotides, and to distinguish activating and repressive
      nucleotides, using their inferred contribution to reporter gene expression. We
      used Sharpr-MPRA to test 4.6 million nucleotides spanning 15,000 putative
      regulatory regions tiled at 5-nucleotide resolution in two human cell types. Our
      results recovered known cell-type-specific regulatory motifs and evolutionarily
      conserved nucleotides, and distinguished known activating and repressive motifs.
      Our results also showed that endogenous chromatin state and DNA accessibility are
      both predictive of regulatory function in reporter assays, identified retroviral
      elements with activating roles, and uncovered 'attenuator' motifs with repressive
      roles in active chromatin.

PMID- 27701404
TI  - A multicenter study benchmarks software tools for label-free proteome
      quantification.
AB  - Consistent and accurate quantification of proteins by mass spectrometry (MS)
      based proteomics depends on the performance of instruments, acquisition methods
      and data analysis software. In collaboration with the software developers, we
      evaluated OpenSWATH, SWATH 2.0, Skyline, Spectronaut and DIA-Umpire, five of the
      most widely used software methods for processing data from sequential window
      acquisition of all theoretical fragment-ion spectra (SWATH)-MS, which uses data
      independent acquisition (DIA) for label-free protein quantification. We analyzed
      high-complexity test data sets from hybrid proteome samples of defined
      quantitative composition acquired on two different MS instruments using different
      SWATH isolation-window setups. For consistent evaluation, we developed LFQbench,
      an R package, to calculate metrics of precision and accuracy in label-free
      quantitative MS and report the identification performance, robustness and
      specificity of each software tool. Our reference data sets enabled developers to
      improve their software tools. After optimization, all tools provided highly
      convergent identification and reliable quantification performance, underscoring
      their robustness for label-free quantitative proteomics.

PMID- 27701405
TI  - Membrane lipidomics in schizophrenia patients: a correlational study with
      clinical and cognitive manifestations.
AB  - Schizophrenia is a severe mental condition in which several lipid abnormalities
      either structural or metabolic-have been described. We tested the hypothesis that
      an abnormality in membrane lipid composition may contribute to aberrant dopamine
      signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ)
      patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74)
      were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was
      performed in red blood cell (RBC) membranes examining the major phospholipid (PL)
      classes and their associated fatty acids (FAs). Clinical manifestations were
      examined using the positive and negative syndrome scale (PANSS). Cognitive
      function was assessed using the Continuous Performance Test, Salience Attribution
      Test and Wisconsin Card Sorting Test. Sphingomyelin (SM) percentage was the lipid
      abnormality most robustly associated with a schizophrenia diagnosis. Two groups
      of patients were defined. The first group (SCZ c/SM-) is characterized by a low
      SM membrane content. In this group, all other PL classes, plasmalogen and key
      polyunsaturated FAs known to be involved in brain function, were significantly
      modified, identifying a very specific membrane lipid cluster. The second patient
      group (SCZ c/SM+) was similar to HCs in terms of RBC membrane SM composition.
      Compared with SCZ c/SM+, SCZ c/SM- patients were characterized by significantly
      more severe PANSS total, positive, disorganized/cognitive and excited
      psychopathology. Cognitive performance was also significantly poorer in this
      subgroup. These data show that a specific RBC membrane lipid cluster is
      associated with clinical and cognitive manifestations of dopamine dysfunction in
      schizophrenia patients. We speculate that this membrane lipid abnormality
      influences presynaptic dopamine signaling.

PMID- 27701406
TI  - Impaired GABA synthesis, uptake and release are associated with depression-like
      behaviors induced by chronic mild stress.
AB  - Major depression is a prevalent emotion disorder. Chronic stressful life in
      genetically susceptible individuals is presumably a major etiology that leads to
      neuron and synapse atrophy in the limbic system. Molecular mechanisms underlying
      the pathological changes remain elusive. Mice were treated by chronic
      unpredictable mild stress (CUMS) until they demonstrated depression-like
      behavior. GABA release in the medial prefrontal cortex was evaluated by cell
      electrophysiology and imaging. Molecular profiles related to GABA synthesis and
      uptake were investigated by the high-throughput sequencings of microRNAs and
      mRNAs as well as western blot analysis in this cortical area. In CUMS-induced
      depression mice, there appear the decreases in the innervation and function of
      GABAergic axons and in the levels of mRNAs and proteins of glutamate
      decarboxylase-67, vesicular GABA transporter and GABA transporter-3. miRNA-15b
      5p, miRNA-144-3p, miRNA-582-5p and miRNA-879-5p that directly downregulate such
      mRNAs increase in this cortex. Our results suggest that chronic mild stress
      impairs GABA release and uptake by upregulating miRNAs and downregulating mRNAs
      and proteins, which may constitute the subcellular and molecular mechanisms for
      the lowered GABA tone in major depression.

PMID- 27701407
TI  - Gene expression alterations related to mania and psychosis in peripheral blood of
      patients with a first episode of psychosis.
AB  - Psychotic disorders affect ~3% of the general population and are among the most
      severe forms of mental diseases. In early stages of psychosis, clinical aspects
      may be difficult to distinguish from one another. Undifferentiated
      psychopathology at the first-episode of psychosis (FEP) highlights the need for
      biomarkers that can improve and refine differential diagnosis. We investigated
      gene expression differences between patients with FEP-schizophrenia spectrum
      (SCZ; N=53) or FEP-Mania (BD; N=16) and healthy controls (N=73). We also verified
      whether gene expression was correlated to severity of psychotic, manic,
      depressive symptoms and/or functional impairment. All participants were
      antipsychotic-naive. After the psychiatric interview, blood samples were
      collected and the expression of 12 psychotic-disorder-related genes was evaluated
      by quantitative PCR. AKT1 and DICER1 expression levels were higher in BD patients
      compared with that in SCZ patients and healthy controls, suggesting that
      expression of these genes is associated more specifically to manic features.
      Furthermore, MBP and NDEL1 expression levels were higher in SCZ and BD patients
      than in healthy controls, indicating that these genes are psychosis related
      (independent of diagnosis). No correlation was found between gene expression and
      severity of symptoms or functional impairment. Our findings suggest that genes
      related to neurodevelopment are altered in psychotic disorders, and some might
      support the differential diagnosis between schizophrenia and bipolar disorder,
      with a potential impact on the treatment of these disorders.

PMID- 27701408
TI  - Enhanced sensitivity to drugs of abuse and palatable foods following maternal
      overnutrition.
AB  - Epidemiological studies have shown an association between maternal overnutrition
      and increased risk of the progeny for the development of obesity as well as
      psychiatric disorders. Animal studies have shown results regarding maternal high
      fat diet (HFD) and a greater risk of the offspring to develop obesity. However,
      it still remains unknown whether maternal HFD can program the central reward
      system in such a way that it will imprint long-term changes that will predispose
      the offspring to addictive-like behaviors that may lead to obesity. We exposed
      female dams to either laboratory chow or HFD for a period of 9 weeks: 3 weeks
      before conception, during gestation and lactation. Offspring born to either
      control or HFD-exposed dams were examined in behavioral, neurochemical,
      neuroanatomical, metabolic and positron emission tomography (PET) scan tests. Our
      results demonstrate that HFD offspring compared with controls consume more
      alcohol, exhibit increased sensitivity to amphetamine and show greater
      conditioned place preference to cocaine. In addition, maternal HFD leads to
      increased preference to sucrose as well as to HFD while leaving the general
      feeding behavior intact. The hedonic behavioral alterations are accompanied by
      reduction of striatal dopamine and by increased dopamine 2 receptors in the same
      brain region as evaluated by post-mortem neurochemical, immunohistochemical as
      well as PET analyses. Taken together, our data suggest that maternal
      overnutrition predisposes the offspring to develop hedonic-like behaviors to both
      drugs of abuse as well as palatable foods and that these types of behaviors may
      share common neuronal underlying mechanisms that can lead to obesity.

PMID- 27701409
TI  - RGS2 expression predicts amyloid-beta sensitivity, MCI and Alzheimer's disease:
      genome-wide transcriptomic profiling and bioinformatics data mining.
AB  - Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded
      protein pathological hallmarks of AD are brain deposits of amyloid-beta (Abeta)
      plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the
      role of Abeta in AD pathology have been raised as Abeta is a common component of
      extracellular brain deposits found, also by in vivo imaging, in non-demented aged
      individuals. It has been suggested that some individuals are more prone to Abeta
      neurotoxicity and hence more likely to develop AD when aging brains start
      accumulating Abeta plaques. Here, we applied genome-wide transcriptomic profiling
      of lymphoblastoid cells lines (LCLs) from healthy individuals and AD patients for
      identifying genes that predict sensitivity to Abeta. Real-time PCR validation
      identified 3.78-fold lower expression of RGS2 (regulator of G-protein signaling
      2; P=0.0085) in LCLs from healthy individuals exhibiting high vs low Abeta
      sensitivity. Furthermore, RGS2 showed 3.3-fold lower expression (P=0.0008) in AD
      LCLs compared with controls. Notably, RGS2 expression in AD LCLs correlated with
      the patients' cognitive function. Lower RGS2 expression levels were also
      discovered in published expression data sets from postmortem AD brain tissues as
      well as in mild cognitive impairment and AD blood samples compared with controls.
      In conclusion, Abeta sensitivity phenotyping followed by transcriptomic profiling
      and published patient data mining identified reduced peripheral and brain
      expression levels of RGS2, a key regulator of G-protein-coupled receptor
      signaling and neuronal plasticity. RGS2 is suggested as a novel AD biomarker
      (alongside other genes) toward early AD detection and future disease modifying
      therapeutics.

PMID- 27701410
TI  - Brain-derived neurotrophic factor protects against tau-related neurodegeneration
      of Alzheimer's disease.
AB  - Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role
      in the pathogenesis of Alzheimer's disease (AD), which is characterized with the
      formation of neuritic plaques consisting of amyloid-beta (Abeta) and
      neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing
      body of evidence indicates a potential protective effect of BDNF against Abeta
      induced neurotoxicity in AD mouse models. However, the direct therapeutic effect
      of BDNF supplement on tauopathy in AD remains to be established. Here, we found
      that the BDNF level was reduced in the serum and brain of AD patients and P301L
      transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of
      adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved
      stable expression of BDNF gene and restored the BDNF level in the brains of P301L
      mice. Restoration of the BDNF level attenuated behavioral deficits, prevented
      neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality,
      but did not affect tau hyperphosphorylation level in the brains of P301L mice.
      Long-term expression of AAV-BDNF in the brain was well tolerated by the mice.
      These findings suggest that the gene delivery of BDNF is a promising treatment
      for tau-related neurodegeneration for AD and other neurodegenerative disorders
      with tauopathy.

PMID- 27701412
TI  - Correction: Combating a Global Threat to a Clonal Crop: Banana Black Sigatoka
      Pathogen Pseudocercospora fijiensis (Synonym Mycosphaerella fijiensis) Genomes
      Reveal Clues for Disease Control.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1005876.].

PMID- 27701411
TI  - Associative Mechanisms Allow for Social Learning and Cultural Transmission of
      String Pulling in an Insect.
AB  - Social insects make elaborate use of simple mechanisms to achieve seemingly
      complex behavior and may thus provide a unique resource to discover the basic
      cognitive elements required for culture, i.e., group-specific behaviors that
      spread from "innovators" to others in the group via social learning. We first
      explored whether bumblebees can learn a nonnatural object manipulation task by
      using string pulling to access a reward that was presented out of reach. Only a
      small minority "innovated" and solved the task spontaneously, but most bees were
      able to learn to pull a string when trained in a stepwise manner. In addition,
      naive bees learnt the task by observing a trained demonstrator from a distance.
      Learning the behavior relied on a combination of simple associative mechanisms
      and trial-and-error learning and did not require "insight": naive bees failed a
      "coiled-string experiment," in which they did not receive instant visual feedback
      of the target moving closer when tugging on the string. In cultural diffusion
      experiments, the skill spread rapidly from a single knowledgeable individual to
      the majority of a colony's foragers. We observed that there were several
      sequential sets ("generations") of learners, so that previously naive observers
      could first acquire the technique by interacting with skilled individuals and,
      subsequently, themselves become demonstrators for the next "generation" of
      learners, so that the longevity of the skill in the population could outlast the
      lives of informed foragers. This suggests that, so long as animals have a basic
      toolkit of associative and motor learning processes, the key ingredients for the
      cultural spread of unusual skills are already in place and do not require
      sophisticated cognition.

PMID- 27701414
TI  - Sailing in Uncharted Waters: Carefully Navigating the Polio Endgame.
AB  - In a Perspective linked to the research article by Isobel Blake and colleagues,
      Elizabeth Miller and T. Jacob John discuss the path towards global polio
      eradication and the challenges, strategies, and necessary precautions around oral
      polio vaccine cessation.

PMID- 27701413
TI  - Neuropsin Inactivation Has Protective Effects against Depressive-Like Behaviours
      and Memory Impairment Induced by Chronic Stress.
AB  - Mounting evidence suggests the interaction between stress and genetics contribute
      to the development of depressive symptoms. Currently, the molecular mechanisms
      mediating this process are poorly understood, hindering the development of new
      clinical interventions. Here, we investigate the interaction between neuropsin, a
      serine protease, and chronic stress on the development of depressive-like
      behaviours in mice. We found no difference in baseline behaviour between
      neuropsin knockout and wild-type mice. However, our results show that neuropsin
      knockout mice are protected against the development of depressive-like behaviours
      and memory impairment following chronic stress. We hypothesised that this
      difference in behaviour may be due to an interaction between neuropsin and
      elevated plasma corticosterone. To test this, we subjected mice to chronic
      corticosterone injections. These injections resulted in changes to hippocampal
      structure similar to that observed following chronic stress. We found that
      inactivation of neuropsin limits the extent of these anatomical changes in both
      the chronic stress and the corticosterone injection exposed cohorts. We next used
      viral vectors to knockdown or overexpress neuropsin in the hippocampus to confirm
      the results of the KO study. Additionally, we found that inactivation of
      neuropsin limited glutamate dysregulation, associated with increased generation
      of reactive oxygen species, resulting from prolonged elevated plasma
      corticosterone. In this study, we demonstrate that neuropsin inactivation
      protects against the impairment of hippocampal functions and the depressive-like
      behaviour induced by chronic stress or high levels of corticosterone.
      Consequently, we suggest neuropsin is a potential target for clinical
      interventions for the management of stress disorders.

PMID- 27701415
TI  - A Prospective Study of Comparing Multi-Gene Biomarker Chip and Serum
      Carcinoembryonic Antigen in the Postoperative Surveillance for Patients with
      Stage I-III Colorectal Cancer.
AB  - BACKGROUND: Circulating biomarkers can predict clinical outcomes in colorectal
      cancer patients. The aim of the study was to evaluate the feasibility of our
      multigene biomarker chip for detecting circulating tumor cells for postoperative
      surveillance of stage I-III colorectal cancer patients. MATERIALS AND METHODS: In
      total, 298 stage I-III colorectal cancer patients were analyzed after curative
      resection between June 2010 and October 2014. During each follow-up, a
      postoperative surveillance strategy, including ESMO Guidelines Working Group
      recommendations and the biochip, was used. RESULTS: After a 28.4-month median
      follow-up, 48 (16.1%) patients had postoperative relapse. Univariate analysis
      revealed that the postoperative relapse risk factors were rectal tumor,
      perineural invasion, elevated preoperative and postoperative serum
      carcinoembryonic antigen levels, and positive biochip results (all P < 0.05).
      Multivariate analyses revealed that postoperative relapse correlated
      significantly with elevated postoperative serum carcinoembryonic antigen levels
      (odds ratio = 4.136, P = 0.008) and positive biochip results (odds ratio =
      66.878, P < 0.001). However, the sensitivity (P = 0.003), specificity (P =
      0.003), positive (P = 0.002) and negative (P = 0.006) predictive values, and
      accuracy (P < 0.001) of the biochip for predicting postoperative relapse were
      significantly higher than those of elevated postoperative serum carcinoembryonic
      antigen levels. Moreover, the median lead time between positive biochip result
      and postoperative relapse detection was significantly earlier than that between
      elevated postoperative serum carcinoembryonic antigen level and postoperative
      relapse detection (10.7 vs. 2.8 months, P < 0.001). Furthermore, positive biochip
      results correlated strongly with lower disease-free survival and overall survival
      of colorectal cancer patients (both P < 0.001). CONCLUSION: Compared with
      conventional serum carcinoembryonic antigen detection, our multigene chip aided
      more accurate and earlier prediction of postoperative relapse during stage I-III
      colorectal cancer patient surveillance. In clinical practice, this biochip may
      facilitate early postoperative relapse diagnosis in colorectal cancer patients.

PMID- 27701416
TI  - Clinical Phenotypes and Comorbidity in European Sleep Apnoea Patients.
AB  - BACKGROUND: Clinical presentation phenotypes of obstructive sleep apnoea (OSA)
      and their association with comorbidity as well as impact on adherence to
      continuous positive airway pressure (CPAP) treatment have not been established.
      METHODS: A prospective follow-up cohort of adult patients with OSA (apnoea
      hypopnoea index (AHI) of >=5/h) from 17 European countries and Israel (n = 6,555)
      was divided into four clinical presentation phenotypes based on daytime symptoms
      labelled as excessive daytime sleepiness ("EDS") and nocturnal sleep problems
      other than OSA (labelled as "insomnia"): 1) EDS (daytime+/nighttime-), 2)
      EDS/insomnia (daytime+/nighttime+), 3) non-EDS/non-insomnia (daytime-/nighttime
      ), 4) and insomnia (daytime-/nighttime+) phenotype. RESULTS: The EDS phenotype
      comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/insomnia type
      23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical
      presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only
      5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less
      prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%,
      p<0.001) despite more severe OSA in the EDS group (AHI 35.0+/-25.5/h vs. 27.9+/
      22.5/h, p<0.001, respectively). Psychiatric comorbidity was associated with
      insomnia like OSA phenotypes independent of age, gender and body mass index (HR
      1.5 (1.188-1.905), p<0.001). The EDS phenotype tended to associate with higher
      CPAP usage (22.7 min/d, p = 0.069) when controlled for age, gender, BMI and sleep
      apnoea severity. CONCLUSIONS: Phenotypes with insomnia symptoms comprised more
      than half of OSA patients and were more frequently linked with comorbidity than
      those with EDS, despite less severe OSA. CPAP usage was slightly higher in
      phenotypes with EDS.

PMID- 27701418
TI  - Role of Recruitment Processes in Structuring Coralligenous Benthic Assemblages in
      the Northern Adriatic Continental Shelf.
AB  - Coralligenous biogenic reefs are among the most diverse marine habitats in the
      Mediterranean Sea. The northern Adriatic mesophotic coralligenous outcrops host
      very rich and diverse epibenthic assemblages. Several studies quantified the low
      temporal variability and high spatial heterogeneity of these habitats, while
      processes driving structuring and differentiation are still poorly understood. To
      shed light on these processes, temporal and spatial patterns of colonisation were
      investigated using travertine tiles deployed on three coralligenous outcrops,
      corresponding to the main typologies of benthic assemblages described in previous
      studies. Three years after deployment, assemblages colonising travertine tiles
      resembled the differentiation among sites revealed by the natural assemblages in
      terms of major ecological groups. Processes structuring and maintaining species
      diversity have been explored. Pioneer species with high reproduction rate, long
      distance larval dispersal and fast growth (e.g. the serpulid polychaete
      Spirobranchus triqueter and the bivalve Anomia ephippium), were the most abundant
      in the early stages of recruitment on the two outcrops further away from the
      coast and with lower sedimentation. Their success may vary according to larval
      availability and environmental conditions (e.g., sedimentation rates). At these
      sites early-stage lasted 10-12 months, during which even species from natural
      substrates began colonising tiles by settlement of planktonic propagules (e.g.,
      encrusting calcareous Rhodophyta) and lateral encroachment (e.g., sponges and
      ascidians). On coastal outcrop, exposed to a higher sedimentation rates, tiles
      were colonised by fast-growing algal turfs. Resilience of northern Adriatic
      coralligenous assemblages, and maintenance of their diversity, appeared largely
      entrusted to asexual reproduction. Exploring the mechanisms that underlie the
      formation and maintenance of the species diversity is crucial to improve our
      understanding of ecological processes and to implement appropriate conservation
      strategies of the Adriatic coralligenous reefs.

PMID- 27701417
TI  - Pyrophosphate Stimulates Differentiation, Matrix Gene Expression and Alkaline
      Phosphatase Activity in Osteoblasts.
AB  - Pyrophosphate is a potent mitogen, capable of stimulating proliferation in
      multiple cell types, and a critical participant in bone mineralization.
      Pyrophosphate can also affect the resorption rate and bioactivity of orthopedic
      ceramics. The present study investigated whether calcium pyrophosphate affected
      proliferation, differentiation and gene expression in early (MC3T3 pre
      osteoblast) and late stage (SAOS-2 osteosarcoma) osteoblasts. Pyrophosphate
      stimulated peak alkaline phosphatase activity by 50% and 150% at 100MUM and
      0.1MUM in MC3T3, and by 40% in SAOS-2. The expression of differentiation markers
      collagen 1 (COL1), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin
      (OCN) were increased by an average of 1.5, 2, 2 and 3 fold, by high
      concentrations of sodium pyrophosphate (100MUM) after 7 days of exposure in
      MC3T3. COX-2 and ANK expression did not differ significantly from controls in
      either treatment group. Though both high and low concentrations of pyrophosphate
      stimulate ALP activity, only high concentrations (100MUM) stimulated osteogenic
      gene expression. Pyrophosphate did not affect proliferation in either cell type.
      The results of this study confirm that chronic exposure to pyrophosphate exerts a
      physiological effect upon osteoblast differentiation and ALP activity,
      specifically by stimulating osteoblast differentiation markers and extracellular
      matrix gene expression.

PMID- 27701419
TI  - Diverging Trends in Cause-Specific Mortality and Life Years Lost by Educational
      Attainment: Evidence from United States Vital Statistics Data, 1990-2010.
AB  - BACKGROUND: Life expectancy at birth in the United States will likely surpass 80
      years in the coming decade. Yet recent studies suggest that longevity gains are
      unevenly shared across age and socioeconomic groups. First, mortality in midlife
      has risen among non-Hispanic whites. Second, low-educated whites have suffered
      stalls (men) or declines (women) in adult life expectancy, which is significantly
      lower than among their college-educated counterparts. Estimating the number of
      life years lost or gained by age and cause of death, broken down by educational
      attainment, is crucial in identifying vulnerable populations. METHODS AND
      FINDINGS: Using U.S. vital statistics data from 1990 to 2010, this study
      decomposes the change in life expectancy at age 25 by age and cause of death
      across educational attainment groups, broken down by race and gender. The
      findings reveal that mortality in midlife increased for white women (and to a
      lesser extent men) with 12 or fewer years of schooling, accounting for most of
      the stalls or declines in adult life expectancy observed in those groups. Among
      blacks, mortality declined in nearly all age and educational attainment groups.
      Although an educational gradient was found across multiple causes of death,
      between 60 and 80 percent of the gap in adult life expectancy was explained by
      cardiovascular diseases, smoking-related diseases, and external causes of death.
      Furthermore, the number of life years lost to smoking-related, external, and
      other causes of death increased among low- and high school-educated whites,
      explaining recent stalls or declines in longevity. CONCLUSIONS: Large segments of
      the American population-particularly low- and high school-educated whites under
      age 55-are diverging from their college-educated counterparts and losing
      additional years of life to smoking-related diseases and external causes of
      death. If this trend continues, old-age mortality may also increase for these
      birth cohorts in the coming decades.

PMID- 27701420
TI  - Characterization of Novel Antimalarial Compound ACT-451840: Preclinical
      Assessment of Activity and Dose-Efficacy Modeling.
AB  - BACKGROUND: Artemisinin resistance observed in Southeast Asia threatens the
      continued use of artemisinin-based combination therapy in endemic countries.
      Additionally, the diversity of chemical mode of action in the global portfolio of
      marketed antimalarials is extremely limited. Addressing the urgent need for the
      development of new antimalarials, a chemical class of potent antimalarial
      compounds with a novel mode of action was recently identified. Herein, the
      preclinical characterization of one of these compounds, ACT-451840, conducted in
      partnership with academic and industrial groups is presented. METHOD AND
      FINDINGS: The properties of ACT-451840 are described, including its spectrum of
      activities against multiple life cycle stages of the human malaria parasite
      Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well
      as oral in vivo efficacies in two murine malaria models that permit infection
      with the human and the rodent parasites P. falciparum and Plasmodium berghei,
      respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4
      nM (standard deviation [SD]: +/- 0.0 nM) against the drug-sensitive P. falciparum
      NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7
      mg/kg against P. falciparum (95% confidence interval: 3.3-4.9 mg/kg) and 13 mg/kg
      against P. berghei (95% confidence interval: 11-16 mg/kg). ACT-451840 potently
      prevented male gamete formation from the gametocyte stage with a 50% inhibition
      concentration of 5.89 nM (SD: +/- 1.80 nM) and dose-dependently blocked oocyst
      development in the mosquito with a 50% inhibitory concentration of 30 nM (range:
      23-39). The compound's preclinical safety profile is presented and is in line
      with the published results of the first-in-man study in healthy male
      participants, in whom ACT-451840 was well tolerated.
      Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in
      the murine models (defined either as antimalarial activity or as survival) in
      relation to area under the concentration versus time curve (AUC), maximum
      observed plasma concentration (Cmax), and time above a threshold concentration.
      The determination of the dose-efficacy relationship of ACT-451840 under curative
      conditions in rodent malaria models allowed prediction of the human efficacious
      exposure. CONCLUSION: The dual activity of ACT-451840 against asexual and sexual
      stages of P. falciparum and the activity on P. vivax have the potential to meet
      the specific profile of a target compound that could replace the fast-acting
      artemisinin component and harbor additional gametocytocidal activity and,
      thereby, transmission-blocking properties. The fast parasite reduction ratio
      (PRR) and gametocytocidal effect of ACT-451840 were recently also confirmed in a
      clinical proof-of-concept (POC) study.

PMID- 27701421
TI  - Cardio-Thoracic Ratio Is Stable, Reproducible and Has Potential as a Screening
      Tool for HIV-1 Related Cardiac Disorders in Resource Poor Settings.
AB  - BACKGROUND: Cardiovascular disorders are common in HIV-1 infected persons in
      Africa and presentation is often insidious. Development of screening algorithms
      for cardiovascular disorders appropriate to a resource-constrained setting could
      facilitate timely referral. Cardiothoracic ratio (CTR) on chest radiograph (CXR)
      has been suggested as a potential screening tool but little is known about its
      reproducibility and stability. Our primary aim was to evaluate the stability and
      the inter-observer variability of CTR in HIV-1 infected outpatients. We further
      evaluated the prevalence of cardiomegaly (CTR>=0.5) and its relationship with
      other risk factors in this population. METHODOLOGY: HIV-1 infected participants
      were identified during screening for a tuberculosis vaccine trial in Khayelitsha,
      South Africa between August 2011 and April 2012. Participants had a digital
      posterior-anterior CXR performed as well as history, examination and baseline
      observations. CXRs were viewed using OsiriX software and CTR calculated using
      digital callipers. RESULTS: 450 HIV-1-infected adults were evaluated, median age
      34 years (IQR 30-40) with a CD4 count 566/mm3 (IQR 443-724), 70% on
      antiretroviral therapy (ART). The prevalence of cardiomegaly was 12.7% (95% C.I.
      9.6%-15.8%). CTR was calculated by a 2nd reader for 113 participants,
      measurements were highly correlated r = 0.95 (95% C.I. 0.93-0.97) and agreement
      of cardiomegaly substantial kappa = 0.78 (95% C.I 0.61-0.95). CXR were repeated
      in 51 participants at 4-12 weeks, CTR measurements between the 2 time points were
      highly correlated r = 0.77 (95% C.I 0.68-0.88) and agreement of cardiomegaly
      excellent kappa = 0.92 (95% C.I. 0.77-1). Participants with cardiomegaly had a
      higher median BMI (31.3; IQR 27.4-37.4) versus 26.9; IQR 23.2-32.4); p<0.0001)
      and median systolic blood pressure (130; IQR 121-141 versus 125; IQR 117-135; p =
      0.01). CONCLUSION: CTR is a robust measurement, stable over time with substantial
      inter-observer agreement. A prospective study evaluating utility of CXR to
      identify cardiovascular disorder in this population is warranted.

PMID- 27701422
TI  - Differential Responses of Post-Exercise Recovery of Leg Blood Flow and Oxygen
      Uptake Kinetics in HFpEF versus HFrEF.
AB  - The goals of the current study were to compare leg blood flow, oxygen extraction
      and oxygen uptake (VO2) after constant load sub-maximal unilateral knee extension
      (ULKE) exercise in patients with heart failure with reduced ejection fraction
      (HFrEF) compared to those with preserved ejection fraction (HFpEF). Previously,
      it has been shown that prolonged whole body VO2 recovery kinetics are directly
      related to disease severity and all-cause mortality in HFrEF patients. To date,
      no study has simultaneously measured muscle-specific blood flow and oxygen
      extraction post exercise recovery kinetics in HFrEF or HFpEF patients; therefore
      it is unknown if muscle VO2 recovery kinetics, and more specifically, the
      recovery kinetics of blood flow and oxygen extraction at the level of the muscle,
      differ between HF phenotypes. Ten older (68+/-10yrs) HFrEF (n = 5) and HFpEF (n =
      5) patients performed sub-maximal (85% of maximal weight lifted during an
      incremental test) ULKE exercise for 4 minutes. Femoral venous blood flow and
      venous O2 saturation were measured continuously from the onset of end-exercise,
      using a novel MRI method, to determine off-kinetics (mean response times, MRT)
      for leg VO2 and its determinants. HFpEF and HFrEF patients had similar end
      exercise leg blood flow (1.1+/-0.6 vs. 1.2+/-0.6 L/min, p>0.05), venous
      saturation (42+/-12 vs. 41+/-11%, p>0.05) and VO2 (0.13+/-0.08 vs. 0.11+/-0.05
      L/min, p>0.05); however HFrEF had significantly delayed recovery MRT for flow
      (292+/-135sec. vs 105+/-63sec., p = 0.004) and VO2 (95+/-37sec. vs. 47+/-15sec.,
      p = 0.005) compared to HFpEF. Impaired muscle VO2 recovery kinetics following
      ULKE exercise differentiated HFrEF from HFpEF patients and suggests distinct
      underlying pathology and potential therapeutic approaches in these populations.

PMID- 27701423
TI  - Whole Genome Sequence Analysis of a Large Isoniazid-Resistant Tuberculosis
      Outbreak in London: A Retrospective Observational Study.
AB  - BACKGROUND: A large isoniazid-resistant tuberculosis outbreak centred on London,
      United Kingdom, has been ongoing since 1995. The aim of this study was to
      investigate the power and value of whole genome sequencing (WGS) to resolve the
      transmission network compared to current molecular strain typing approaches,
      including analysis of intra-host diversity within a specimen, across body sites,
      and over time, with identification of genetic factors underlying the
      epidemiological success of this cluster. METHODS AND FINDINGS: We sequenced 344
      outbreak isolates from individual patients collected over 14 y (2 February 1998
      22 June 2012). This demonstrated that 96 (27.9%) were indistinguishable, and only
      one differed from this major clone by more than five single nucleotide
      polymorphisms (SNPs). The maximum number of SNPs between any pair of isolates was
      nine SNPs, and the modal distance between isolates was two SNPs. WGS was able to
      reveal the direction of transmission of tuberculosis in 16 cases within the
      outbreak (4.7%), including within a multidrug-resistant cluster that carried a
      rare rpoB mutation associated with rifampicin resistance. Eleven longitudinal
      pairs of patient pulmonary isolates collected up to 48 mo apart differed from
      each other by between zero and four SNPs. Extrapulmonary dissemination resulted
      in acquisition of a SNP in two of five cases. WGS analysis of 27 individual
      colonies cultured from a single patient specimen revealed ten loci differed
      amongst them, with a maximum distance between any pair of six SNPs. A limitation
      of this study, as in previous studies, is that indels and SNPs in repetitive
      regions were not assessed due to the difficulty in reliably determining this
      variation. CONCLUSIONS: Our study suggests that (1) certain paradigms need to be
      revised, such as the 12 SNP distance as the gold standard upper threshold to
      identify plausible transmissions; (2) WGS technology is helpful to rule out the
      possibility of direct transmission when isolates are separated by a substantial
      number of SNPs; (3) the concept of a transmission chain or network may not be
      useful in institutional or household settings; (4) the practice of isolating
      single colonies prior to sequencing is likely to lead to an overestimation of the
      number of SNPs between cases resulting from direct transmission; and (5) despite
      appreciable genomic diversity within a host, transmission of tuberculosis rarely
      results in minority variants becoming dominant. Thus, whilst WGS provided some
      increased resolution over variable number tandem repeat (VNTR)-based clustering,
      it was insufficient for inferring transmission in the majority of cases.

PMID- 27701425
TI  - Population Immunity against Serotype-2 Poliomyelitis Leading up to the Global
      Withdrawal of the Oral Poliovirus Vaccine: Spatio-temporal Modelling of
      Surveillance Data.
AB  - BACKGROUND: Global withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took
      place in April 2016. This marked a milestone in global polio eradication and was
      a public health intervention of unprecedented scale, affecting 155 countries.
      Achieving high levels of serotype-2 population immunity before OPV2 withdrawal
      was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived
      polioviruses (VDPV2s). METHODS AND FINDINGS: In August 2015, we estimated vaccine
      induced population immunity against serotype-2 poliomyelitis for 1 January 2004
      30 June 2015 and produced forecasts for April 2016 by district in Nigeria and
      Pakistan. Population immunity was estimated from the vaccination histories of
      children <36 mo old identified with non-polio acute flaccid paralysis (AFP)
      reported through polio surveillance, information on immunisation activities with
      different oral poliovirus vaccine (OPV) formulations, and serotype-specific
      estimates of the efficacy of these OPVs against poliomyelitis. District immunity
      estimates were spatio-temporally smoothed using a Bayesian hierarchical
      framework. Coverage estimates for immunisation activities were also obtained,
      allowing for heterogeneity within and among districts. Forward projections of
      immunity, based on these estimates and planned immunisation activities, were
      produced through to April 2016 using a cohort model. Estimated population
      immunity was negatively correlated with the probability of VDPV2 poliomyelitis
      being reported in a district. In Nigeria and Pakistan, declines in immunity
      during 2008-2009 and 2012-2013, respectively, were associated with outbreaks of
      VDPV2. Immunity has since improved in both countries as a result of increased use
      of trivalent OPV, and projections generally indicated sustained or improved
      immunity in April 2016, such that the majority of districts (99% [95% uncertainty
      interval 97%-100%] in Nigeria and 84% [95% uncertainty interval 77%-91%] in
      Pakistan) had >70% population immunity among children <36 mo old. Districts with
      lower immunity were clustered in northeastern Nigeria and northwestern Pakistan.
      The accuracy of immunity estimates was limited by the small numbers of non-polio
      AFP cases in some districts, which was reflected by large uncertainty intervals.
      Forecasted improvements in immunity for April 2016 were robust to the uncertainty
      in estimates of baseline immunity (January-June 2015), vaccine coverage, and
      vaccine efficacy. CONCLUSIONS: Immunity against serotype-2 poliomyelitis was
      forecasted to improve in April 2016 compared to the first half of 2015 in Nigeria
      and Pakistan. These analyses informed the endorsement of OPV2 withdrawal in April
      2016 by the WHO Strategic Advisory Group of Experts on Immunization.

PMID- 27701426
TI  - Coupled Hybrid Continuum-Discrete Model of Tumor Angiogenesis and Growth.
AB  - The processes governing tumor growth and angiogenesis are codependent. To study
      the relationship between them, we proposed a coupled hybrid continuum-discrete
      model. In this model, tumor cells, their microenvironment (extracellular
      matrixes, matrix-degrading enzymes, and tumor angiogenic factors), and their
      network of blood vessels, described by a series of discrete points, were
      considered. The results of numerical simulation reveal the process of tumor
      growth and the change in microenvironment from avascular to vascular stage,
      indicating that the network of blood vessels develops gradually as the tumor
      grows. Our findings also reveal that a tumor is divided into three regions:
      necrotic, semi-necrotic, and well-vascularized. The results agree well with the
      previous relevant studies and physiological facts, and this model represents a
      platform for further investigations of tumor therapy.

PMID- 27701424
TI  - Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis.
AB  - Osteoarthritis is one of the most frequent and disabling diseases of the elderly.
      Only few genetic variants have been identified for osteoarthritis, which is
      partly due to large phenotype heterogeneity. To reduce heterogeneity, we here
      examined cartilage thickness, one of the structural components of joint health.
      We conducted a genome-wide association study of minimal joint space width (mJSW),
      a proxy for cartilage thickness, in a discovery set of 13,013 participants from
      five different cohorts and replication in 8,227 individuals from seven
      independent cohorts. We identified five genome-wide significant (GWS, P<=5.0*10
      8) SNPs annotated to four distinct loci. In addition, we found two additional
      loci that were significantly replicated, but results of combined meta-analysis
      fell just below the genome wide significance threshold. The four novel associated
      genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753),
      SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and
      SUPT3H/RUNX2) were previously identified. A systematic prioritization for
      underlying causal genes was performed using diverse lines of evidence. Exome
      sequencing data (n = 2,050 individuals) indicated that there were no rare exonic
      variants that could explain the identified associations. In addition, TGFA, FGFR3
      and PIK3R1 were differentially expressed in OA cartilage lesions versus non
      lesioned cartilage in the same individuals. In conclusion, we identified four
      novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be
      associated with cartilage thickness.The identified associations were not caused
      by rare exonic variants. This is the first report linking TGFA to human OA, which
      may serve as a new target for future therapies.

PMID- 27701427
TI  - Asymmetric Power Boosts Extortion in an Economic Experiment.
AB  - Direct reciprocity is a major mechanism for the evolution of cooperation. Several
      classical studies have suggested that humans should quickly learn to adopt
      reciprocal strategies to establish mutual cooperation in repeated interactions.
      On the other hand, the recently discovered theory of ZD strategies has found that
      subjects who use extortionate strategies are able to exploit and subdue
      cooperators. Although such extortioners have been predicted to succeed in any
      population of adaptive opponents, theoretical follow-up studies questioned
      whether extortion can evolve in reality. However, most of these studies presumed
      that individuals have similar strategic possibilities and comparable outside
      options, whereas asymmetries are ubiquitous in real world applications. Here we
      show with a model and an economic experiment that extortionate strategies readily
      emerge once subjects differ in their strategic power. Our experiment combines a
      repeated social dilemma with asymmetric partner choice. In our main treatment
      there is one randomly chosen group member who is unilaterally allowed to exchange
      one of the other group members after every ten rounds of the social dilemma. We
      find that this asymmetric replacement opportunity generally promotes cooperation,
      but often the resulting payoff distribution reflects the underlying power
      structure. Almost half of the subjects in a better strategic position turn into
      extortioners, who quickly proceed to exploit their peers. By adapting their
      cooperation probabilities consistent with ZD theory, extortioners force their co
      players to cooperate without being similarly cooperative themselves. Comparison
      to non-extortionate players under the same conditions indicates a substantial net
      gain to extortion. Our results thus highlight how power asymmetries can endanger
      mutually beneficial interactions, and transform them into exploitative
      relationships. In particular, our results indicate that the extortionate
      strategies predicted from ZD theory could play a more prominent role in our daily
      interactions than previously thought.

PMID- 27701428
TI  - Krill Oil Improves Mild Knee Joint Pain: A Randomized Control Trial.
AB  - BACKGROUND: Krill oil is an edible oil extracted from krill, a small red-colored
      crustacean found in the Antarctic Ocean. The administration of krill oil is
      reported to mitigate inflammation in patients with cardiac disease, rheumatoid
      arthritis, or osteoarthritis. However, the effect of krill oil on mild knee pain
      has not yet been determined. OBJECTIVE: To assess the effect of krill oil on mild
      knee pain. DESIGN: A randomized, double-blind, parallel-group, placebo-controlled
      trial of fifty adults (38-85 years old) with mild knee pain attending the
      Fukushima Orthopedic Clinic (Tochigi, Japan) between September 2014 and March
      2015. INTERVENTIONS: Participants were randomized to receive 2 g per day of
      either krill oil or an identical placebo for 30 days. OUTCOMES: The primary
      outcome was improvement in subjective symptoms of knee pain as assessed by the
      Japanese Knee Osteoarthritis Measure (JKOM) and Japanese Orthopaedic Association
      score (JOA). Secondary outcomes included blood and urine biochemical parameters.
      RESULTS: Both the placebo and krill oil groups showed significant improvements in
      the questions in the JKOM and JOA questionnaires after administration. After the
      intervention, krill oil group showed more improvements than placebo group in two
      questions regarding the pain and stiffness in knees in JKOM. Controlling for age,
      sex, weight, and smoking and drinking habits, krill oil significantly mitigated
      knee pain in sleeping (P < 0.001), standing (P < 0.001) and the range of motion
      of both right and left knees (both P = 0.011) compared to placebo. Krill oil
      administration raised plasma EPA (P = 0.048) and EPA/AA ratio (P = 0.003).
      CONCLUSION: This study indicates that krill oil administration (2 g/day, 30 days)
      improved the subjective symptoms of knee pain in adults with mild knee pain.
      TRIAL REGISTRATION: UMIN-CTR; ID UMIN000014413.

PMID- 27701429
TI  - The Global Diversity of Hemichordata.
AB  - Phylum Hemichordata, composed of worm-like Enteropneusta and colonial
      Pterobranchia, has been reported to only contain about 100 species. However,
      recent studies of hemichordate phylogeny and taxonomy suggest the species number
      has been largely underestimated. One issue is that species must be described by
      experts, and historically few taxonomists have studied this group of marine
      invertebrates. Despite this previous lack of coverage, interest in hemichordates
      has piqued in the past couple of decades, as they are critical to understanding
      the evolution of chordates-as acorn worms likely resemble the deuterostome
      ancestor more closely than any other extant animal. This review provides an
      overview of our current knowledge of hemichordates, focusing specifically on
      their global biodiversity, geographic distribution, and taxonomy. Using
      information available in the World Register of Marine Species and published
      literature, we assembled a list of 130 described, extant species. The majority
      (83%) of these species are enteropneusts, and more taxonomic descriptions are
      forthcoming. Ptychoderidae contained the greatest number of species (41 species),
      closely followed by Harrimaniidae (40 species), of the recognized hemichordate
      families. Hemichordates are found throughout the world's oceans, with the highest
      reported numbers by regions with marine labs and diligent taxonomic efforts (e.g.
      North Pacific and North Atlantic). Pterobranchs are abundant in Antarctica, but
      have also been found at lower latitudes. We consider this a baseline report and
      expect new species of Hemichordata will continue to be discovered and described
      as new marine habitats are characterized and explored.

PMID- 27701430
TI  - Empirical Models of Social Learning in a Large, Evolving Network.
AB  - This paper advances theories of social learning through an empirical examination
      of how social networks change over time. Social networks are important for
      learning because they constrain individuals' access to information about the
      behaviors and cognitions of other people. Using data on a large social network of
      mobile device users over a one-month time period, we test three hypotheses: 1)
      attraction homophily causes individuals to form ties on the basis of attribute
      similarity, 2) aversion homophily causes individuals to delete existing ties on
      the basis of attribute dissimilarity, and 3) social influence causes individuals
      to adopt the attributes of others they share direct ties with. Statistical models
      offer varied degrees of support for all three hypotheses and show that these
      mechanisms are more complex than assumed in prior work. Although homophily is
      normally thought of as a process of attraction, people also avoid relationships
      with others who are different. These mechanisms have distinct effects on network
      structure. While social influence does help explain behavior, people tend to
      follow global trends more than they follow their friends.

PMID- 27701431
TI  - The Effect of Age on Technique Variability and Outcome Variability during a Leg
      Press.
AB  - The aim of this study was to determine the effect of aging on power generation
      and joint coordination during a leg press, in order to increase understanding of
      how functional movements are affected during the aging process. 44 older and 24
      younger adults performed eight sub-maximal power repetitions on a seated leg
      press dynamometer. Peak power and velocity (at 40% maximum resistance) were
      measured along with the coordination (coupling angle) of the lower limb joints
      using the vector coding technique. The younger adults produced significantly
      greater peak power than the older adults (mean +/- SD; 762 W +/- 245 vs 361 W +/-
      162, p < 0.01) and at higher peak velocities (mean +/- SD; 1.37 m/s +/- 0.05 vs
      1.00 m/s +/- 0.06, p < 0.01). The older adults produced less consistent values of
      peak power than younger adults, evidenced by a higher coefficient of variation
      (mean +/- SD; 7.6% +/- 5.2 vs 5.0% +/- 3.0, p < 0.01), however, there was
      significantly less variability in the coupling angles displayed by the older
      adults compared to the younger adults (mean +/- SD; 2.0 degrees  +/- 1.1 vs 3.5
      degrees  +/- 2.7, p < 0.01 (ankle-knee); 1.7 degrees  +/- 0.6 vs 4.1 degrees  +/-
      3.0, p < 0.01 (knee-hip)). The results of this study demonstrate that older
      adults display higher outcome variability but lower variability in technique
      (coordination). The more rigid movement strategies displayed by the older adults
      potentially reflects an increased risk of overuse injury due to repetitive
      demands on the same structures, or the reduced ability to respond to unexpected
      situations due to a lack of flexibility in joint control.

PMID- 27701432
TI  - Influence of Endogenous and Exogenous Estrogenic Endocrine on Intestinal
      Microbiota in Zebrafish.
AB  - Gender is one of the factors influencing the intestinal microbial composition in
      mammals, but whether fish also have gender-specific intestinal microbial patterns
      remains unknown. In this decade, endocrine disrupting chemicals in surface and
      ground water of many areas and increasing observation of freshwater male fish
      displaying female sexual characteristics have been reported. Here we identified
      the difference in intestinal microbiota between male and female zebrafish, and
      revealed the influence of endocrine disrupting chemicals on zebrafish intestinal
      microbiota by using high-throughput sequencing. The results indicated that
      Fusobacteria, Bacteroidetes and Proteobacteria were dominant in the gut of
      zebrafish and there were no obvious gender-specific intestinal microbial
      patterns. Two endocrine disrupting chemicals, Estradiol (E2) and Bisphenol A
      (BPA), were selected to treat male zebrafish for 5 weeks. E2 and BPA increased
      vitellogenin expression in the liver of male zebrafish and altered the intestinal
      microbial composition with the abundance of the phylum CKC4 increased
      significantly. Our results suggested that because of the developmental character
      and living environment, gender did not influence the assembly of intestinal
      microbiota in zebrafish as it does in mammals, but exposure extra to endocrine
      disrupting chemicals disturbed the intestinal microbial composition, which may be
      related to changes in host physiological metabolism.

PMID- 27701433
TI  - Strong or Weak Handgrip? Normative Reference Values for the German Population
      across the Life Course Stratified by Sex, Age, and Body Height.
AB  - Handgrip strength is an important biomarker of healthy ageing and a powerful
      predictor of future morbidity and mortality both in younger and older
      populations. Therefore, the measurement of handgrip strength is increasingly used
      as a simple but efficient screening tool for health vulnerability. This study
      presents normative reference values for handgrip strength in Germany for use in
      research and clinical practice. It is the first study to provide normative data
      across the life course that is stratified by sex, age, and body height. The study
      used a nationally representative sample of test participants ages 17-90. It was
      based on pooled data from five waves of the German Socio-Economic Panel (2006
      2014) and involved a total of 11,790 persons living in Germany (providing 25,285
      observations). Handgrip strength was measured with a Smedley dynamometer. Results
      showed that peak mean values of handgrip strength are reached in men's and
      women's 30s and 40s after which handgrip strength declines in linear fashion with
      age. Following published recommendations, the study used a cut-off at 2 SD below
      the sex-specific peak mean value across the life course to define a 'weak grip'.
      Less than 10% of women and men aged 65-69 were classified as weak according to
      this definition, shares increasing to about half of the population aged 80-90.
      Based on survival analysis that linked handgrip strength to a relevant outcome,
      however, a 'critically weak grip' that warrants further examination was estimated
      to commence already at 1 SD below the group-specific mean value.

PMID- 27701434
TI  - Representation of Afferent Signals from Forearm Muscle and Cutaneous Nerves in
      the Primary Somatosensory Cortex of the Macaque Monkey.
AB  - Proprioception is one's overall sense of the relative positions and movements of
      the various parts of one's body. The primary somatosensory cortex (SI) is
      involved in generating the proprioception by receiving peripheral sensory inputs
      from both cutaneous and muscle afferents. In particular, area 3a receives input
      from muscle afferents and areas 3b and 1 from cutaneous afferents. However,
      segregation of two sensory inputs to these cortical areas has not been evaluated
      quantitatively because of methodological difficulties in distinguishing the
      incoming signals. To overcome this, we applied electrical stimulation separately
      to two forearm nerves innervating muscle (deep radial nerve) and skin
      (superficial radial nerve), and examined the spatiotemporal distribution of
      sensory evoked potentials (SEPs) in SI of anaesthetized macaques. The SEPs
      arising from the deep radial nerve were observed exclusively at the bottom of
      central sulcus (CS), which was identified as area 3a using histological
      reconstruction. In contrast, SEPs evoked by stimulation of the superficial radial
      nerve were observed in the superficial part of SI, identified as areas 3b and 1.
      In addition to these earlier, larger potentials, we also found small and slightly
      delayed SEPs evoked by cutaneous nerve stimulation in area 3a. Coexistence of the
      SEPs from both deep and superficial radial nerves suggests that area 3a could
      integrate muscle and cutaneous signals to shape proprioception.

PMID- 27701435
TI  - Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role
      of CD36.
AB  - Macrophages are essential to maintaining lung homoeostasis and recent work has
      demonstrated that influenza-infected lung macrophages downregulate their
      expression of the scavenger receptor CD36. This receptor has also been shown to
      be involved in phagocytosis of Streptococcus pneumoniae, a primary agent
      associated with pneumonia secondary to viral infection. The aim of this study was
      to investigate the role of CD36 in the effects of viral infection on macrophage
      phagocytic function. Human monocyte-derived macrophages (MDM) were exposed to
      H3N2 X31 influenza virus, M37 respiratory syncytial virus (RSV) or UV-irradiated
      virus. No infection of MDM was seen upon exposure to UV-irradiated virus but
      incubation with live X31 or M37 resulted in significant levels of viral detection
      by flow cytometry or RT-PCR respectively. Infection resulted in significantly
      diminished uptake of S. pneumoniae by MDM and significantly decreased expression
      of CD36 at both the cell surface and mRNA level. Concurrently, there was a
      significant increase in IFNbeta gene expression in response to infection and we
      observed a significant decrease in bacterial phagocytosis (p = 0.031) and CD36
      gene expression (p = 0.031) by MDM cultured for 24 h in 50IU/ml IFNbeta.
      Knockdown of CD36 by siRNA resulted in decreased phagocytosis, but this was
      mimicked by transfection reagent alone. When MDM were incubated with CD36
      blocking antibodies no effect on phagocytic ability was observed. These data
      indicate that autologous IFNbeta production by virally-infected cells can inhibit
      bacterial phagocytosis, but that decreased CD36 expression by these cells does
      not play a major role in this functional deficiency.

PMID- 27701436
TI  - hemaClass.org: Online One-By-One Microarray Normalization and Classification of
      Hematological Cancers for Precision Medicine.
AB  - BACKGROUND: Dozens of omics based cancer classification systems have been
      introduced with prognostic, diagnostic, and predictive capabilities. However,
      they often employ complex algorithms and are only applicable on whole cohorts of
      patients, making them difficult to apply in a personalized clinical setting.
      RESULTS: This prompted us to create hemaClass.org, an online web application
      providing an easy interface to one-by-one RMA normalization of microarrays and
      subsequent risk classifications of diffuse large B-cell lymphoma (DLBCL) into
      cell-of-origin and chemotherapeutic sensitivity classes. Classification results
      for one-by-one array pre-processing with and without a laboratory specific RMA
      reference dataset were compared to cohort based classifiers in 4 publicly
      available datasets. Classifications showed high agreement between one-by-one and
      whole cohort pre-processsed data when a laboratory specific reference set was
      supplied. The website is essentially the R-package hemaClass accompanied by a
      Shiny web application. The well-documented package can be used to run the website
      locally or to use the developed methods programmatically. CONCLUSIONS: The
      website and R-package is relevant for biological and clinical lymphoma
      researchers using affymetrix U-133 Plus 2 arrays, as it provides reliable and
      swift methods for calculation of disease subclasses. The proposed one-by-one pre
      processing method is relevant for all researchers using microarrays.

PMID- 27701437
TI  - A New Aspergillus fumigatus Typing Method Based on Hypervariable Tandem Repeats
      Located within Exons of Surface Protein Coding Genes (TRESP).
AB  - Aspergillus fumigatus is a saprotrophic mold fungus ubiquitously found in the
      environment and is the most common species causing invasive aspergillosis in
      immunocompromised individuals. For A. fumigatus genotyping, the short tandem
      repeat method (STRAf) is widely accepted as the first choice. However,
      difficulties associated with PCR product size and required technology have
      encouraged the development of novel typing techniques. In this study, a new
      genotyping method based on hypervariable tandem repeats within exons of surface
      protein coding genes (TRESP) was designed. A. fumigatus isolates were
      characterized by PCR amplification and sequencing with a panel of three TRESP
      encoding genes: cell surface protein A; MP-2 antigenic galactomannan protein; and
      hypothetical protein with a CFEM domain. The allele sequence repeats of each of
      the three targets were combined to assign a specific genotype. For the evaluation
      of this method, 126 unrelated A. fumigatus strains were analyzed and 96 different
      genotypes were identified, showing a high level of discrimination [Simpson's
      index of diversity (D) 0.994]. In addition, 49 azole resistant strains were
      analyzed identifying 26 genotypes and showing a lower D value (0.890) among them.
      This value could indicate that these resistant strains are closely related and
      share a common origin, although more studies are needed to confirm this
      hypothesis. In summary, a novel genotyping method for A. fumigatus has been
      developed which is reproducible, easy to perform, highly discriminatory and could
      be especially useful for studying outbreaks.

PMID- 27701439
TI  - Predictors and Extent of Institutional Trust in Government, Banks, the Media and
      Religious Organisations: Evidence from Cross-Sectional Surveys in Six Asia
      Pacific Countries.
AB  - BACKGROUND: Building or maintaining institutional trust is of central importance
      in democratic societies since negative experiences (potentially leading to
      mistrust) with government or other institutions may have a much more profound
      effect than positive experiences (potentially maintaining trust). Healthy
      democracy relies on more than simply trusting the national government of the
      time, and is mediated through other symbols of institutional power, such as the
      legal system, banks, the media and religious organisations. This paper focuses on
      institutional trust-the level and predictors of trust in some of the major
      institutions in society, namely politics, the media, banks, the legal system and
      religious organisations. We present analyses from a consolidated dataset
      containing data from six countries in the Asia Pacific region-Australia, Hong
      Kong, Japan, South Korea, Taiwan and Thailand. METHODS: Cross-sectional surveys
      were undertaken in each country in 2009-10, with an overall sample of 6331.
      Analyses of differences in overall levels of institutional trust between
      countries were undertaken using Chi square analyses. Multivariate binomial
      logistic regression analysis was undertaken to identify socio-demographic
      predictors of trust in each country. RESULTS: Religious institutions, banks and
      the judicial system had the highest overall trust across all countries (70%, 70%
      and 67% respectively), followed by newspapers and TV (59% and 58%) and then
      political leaders (43%). The range of levels of higher trust between countries
      differed from 43% for banks (range 49% in Australia to 92% in Thailand) to 59%
      for newspapers (28% in Australia to 87% in Japan). Across all countries, except
      for Australia, trust in political leaders had the lowest scores, particularly in
      Japan and South Korea (25% in both countries). In Thailand, people expressed the
      most trust in religious organisations (94%), banks (92%) and in their
      judicial/legal system (89%). In Hong Kong, people expressed the highest level of
      trust in their judicial/legal system (89%), followed by religious organisations
      (75%) and banks (77%). Australian respondents reported the least amount of trust
      in TV/media (24%) and press/newspapers (28%). South Korea put the least trust in
      their political leaders (25%), their legal system (43%) and religious
      organisations (45%). The key predictors of lower trust in institutions across all
      countries were males, people under 44 years and people unsatisfied with the
      health and standard of living. CONCLUSION: We interpreted our data using
      Fukuyama's theory of 'high/low trust' societies. The levels of institutional
      trust in each society did not conform to our hypothesis, with Thailand exhibiting
      the highest trust (predicted to be medium level), Hong Kong and Japan exhibiting
      medium trust (predicted to be low and high respectively) and Australia and South
      Korea exhibiting low trust (predicted to be high and medium respectively). Taiwan
      was the only country where the actual and predicted trust was the same, namely
      low trust. Given the fact that these predictors crossed national boundaries and
      institutional types, further research and policy should focus specifically on
      improving trust within these groups in order that they can be empowered to play a
      more central role in democratic vitality.

PMID- 27701438
TI  - Association of HLA-A and Non-Classical HLA Class I Alleles.
AB  - The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA
      F. HLA class Ib molecules are involved in immuno-modulation with a central role
      for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for
      HLA-H. Thus, the principal objective of this study was to describe the main
      allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, 
      E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region
      haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood
      donors. Allelic frequencies, Global Linkage Disequilibrium (GLD), Linkage
      Disequilibrium (LD) for specific pairs of alleles and two-loci haplotype
      frequencies were estimated. We showed that HLA-A, HLA-H, HLA-F, HLA-G and HLA-G
      UTRs were all in highly significant pairwise GLD, in contrast to HLA-E. Moreover,
      HLA-A displayed restricted associations with HLA-G UTR and HLA-H. We also
      confirmed several associations that were previously found to have a negative
      impact on transplantation outcome. In summary, our results suggest complex
      functional and clinical implications of the HLA-A genetic region.

PMID- 27701440
TI  - Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice.
AB  - Obesity-associated diseases such as Type 2 diabetes, liver disease and
      cardiovascular diseases are profoundly mediated by low-grade chronic inflammation
      of the adipose tissue. Recently, the importance of neutrophils and neutrophil
      derived myeloperoxidase and neutrophil elastase on the induction of insulin
      resistance has been established. Since neutrophil elastase and myeloperoxidase
      are critically involved in the release of neutrophil extracellular traps (NETs),
      we here hypothesized that NETs may be relevant to early adipose tissue
      inflammation. Thus, we tested the effect of the Peptidyl Arginine Deiminase 4
      inhibitor Cl-amidine, a compound preventing histone citrullination and subsequent
      NET release, in a mouse model of adipose tissue inflammation. C57BL6 mice
      received a 60% high fat diet for 10 weeks and were treated with either Cl-amidine
      or vehicle. Flow cytometry of adipose tissue and liver, immunohistological
      analysis and glucose and insulin tolerance tests were performed to determine the
      effect of the treatment and diet. Although high fat diet feeding induced insulin
      resistance no significant effect was observed between the treatment groups. In
      addition no effect was found in leukocyte infiltration and activation in the
      adipose tissue and liver. Therefore we concluded that inhibition of neutrophil
      extracellular trap formation may have no clinical relevance for early obesity
      mediated pathogenesis of the adipose tissue and liver.

PMID- 27701441
TI  - Factors Associated with Visual Fatigue from Curved Monitor Use: A Prospective
      Study of Healthy Subjects.
AB  - PURPOSE: To investigate the factors associated with visual fatigue using monitors
      with various radii of curvature. METHODS: Twenty normal healthy adults (8 men, 12
      women; mean age, 26.2 +/- 2.5 years) prospectively watched five types of monitors
      including flat, 4000R, 3000R, 2000R, and 1000R curved monitors for 30 min. An
      experienced examiner measured the ophthalmological factors including near point
      of accommodation (NPA), near point of convergence (NPC), refraction, parameters
      during pupil response at light and saccadic movement just before and after the
      visual tasks. The questionnaires about subjective ocular symptoms were also
      investigated just before and after the visual tasks. RESULTS: The NPA increased
      after the visual tasks with a flat monitor compared with the curved monitors,
      with the 1000R curved monitor showing the smallest change (p = 0.020). The NPC
      increased for every monitor after the visual tasks; the largest increase occurred
      with the flat monitor (p = 0.001). There was no difference in refractive error,
      pupil response, or saccadic movement in the comparison of before and after the
      visual tasks. Among the nine factors in the questionnaire, the score of "eye
      pain" was significantly higher for the flat monitor versus the 1000R curved
      monitor after the visual tasks (p = 0.034). CONCLUSIONS: We identified NPA, NPC,
      and eye pain as factors associated with visual fatigue. Also, the curvature of
      the monitor was related to the visual fatigue.

PMID- 27701442
TI  - A Longitudinal Operant Assessment of Cognitive and Behavioural Changes in the
      HdhQ111 Mouse Model of Huntington's Disease.
AB  - Huntington's disease (HD) is characterised by motor symptoms which are often
      preceded by cognitive and behavioural changes, that can significantly contribute
      to disease burden for people living with HD. Numerous knock-in mouse models of HD
      are currently available for scientific research. However, before their use, they
      must be behaviourally characterised to determine their suitability in
      recapitulating the symptoms of the human condition. Thus, we sought to
      longitudinally characterise the nature, severity and time course of cognitive and
      behavioural changes observed in HdhQ111 heterozygous knock-in mice.To determine
      changes in cognition and behaviour an extensive battery of operant tests
      including: fixed ratio, progressive ratio, the five choice serial reaction time
      task and the serial implicit learning task, were applied longitudinally to
      HdhQ111 and wild type mice. The operant test battery was conducted at 6, 12 and
      18 months of age. Significant deficits were observed in HdhQ111 animals in
      comparison to wild type animals in all operant tests indicating altered cognition
      (attentional and executive function) and motivation. However, the cognitive and
      behavioural deficits observed were not shown to be progressive over time in the
      longitudinal testing paradigm that was utilised. The results therefore
      demonstrate that the HdhQ111 mouse model of HD reflects some features of the
      cognitive and behavioural changes shown in the human condition of HD. Although,
      the cognitive and behavioural deficits demonstrated were not shown to be
      progressive over time.

PMID- 27701443
TI  - Spatiotemporal Parameters of 100-m Sprint in Different Levels of Sprinters with
      Unilateral Transtibial Amputation.
AB  - The aim of this study was to investigate differences of the spatiotemporal
      parameters in a 100-m sprint among elite, sub-elite, and non-elite sprinters with
      a unilateral transtibial amputation. Using publicly available Internet
      broadcasts, we analyzed 125, 19, and 33 records from 30 elite, 12 sub-elite, and
      22 non-elite sprinters, respectively. For each sprinter's run, the average
      velocity, step frequency, and step length were calculated using the number of
      steps in conjunction with the official race time. Average velocity was greatest
      in elite sprinters (8.71+/-0.32 m/s), followed by the sub-elite (8.09+/-0.06 m/s)
      and non-elite groups (7.72+/-0.27 m/s). Although there was a significant
      difference in average step frequency between the three groups, the effect size
      was small and the relative difference among the three groups was 3.1%.
      Statistical analysis also revealed that the average step length was longest in
      elite sprinters, followed by the sub-elite and non-elite groups. These results
      suggest that the differences in sprint performance between the three groups is
      mainly due to the average step length rather than step frequency.

PMID- 27701444
TI  - Protocadherin-1 Localization and Cell-Adhesion Function in Airway Epithelial
      Cells in Asthma.
AB  - BACKGROUND: The asthma gene PCDH1 encodes Protocadherin-1, a putative adhesion
      molecule of unknown function expressed in the airway epithelium. Here, we
      characterize the localization, differential expression, homotypic adhesion
      specificity and function of PCDH1 in airway epithelial cells in asthma. METHODS:
      We performed confocal fluorescence microscopy to determine subcellular
      localization of PCDH1 in 16HBE cells and primary bronchial epithelial cells
      (PBECs) grown at air-liquid interface. Next, to compare PCDH1 expression and
      localization in asthma and controls we performed qRT-PCR and fluorescence
      microscopy in PBECs and immunohistochemistry on airway wall biopsies. We examined
      homotypic adhesion specificity of HEK293T clones overexpressing fluorescently
      tagged-PCDH1 isoforms. Finally, to evaluate the role for PCDH1 in epithelial
      barrier formation and repair, we performed siRNA knockdown-studies and measured
      epithelial resistance. RESULTS: PCDH1 localized to the cell membrane at cell-cell
      contact sites, baso-lateral to adherens junctions, with increasing expression
      during epithelial differentiation. No differences in gene expression or
      localization of PCDH1 isoforms expressing the extracellular domain were observed
      in either PBECs or airway wall biopsies between asthma patients and controls.
      Overexpression of PCDH1 mediated homotypic interaction, whereas downregulation of
      PCDH1 reduced epithelial barrier formation, and impaired repair after wounding.
      CONCLUSIONS: In conclusion, PCDH1 is localized to the cell membrane of bronchial
      epithelial cells baso-lateral to the adherens junction. Expression of PCDH1 is
      not reduced nor delocalized in asthma even though PCDH1 contributes to homotypic
      adhesion, epithelial barrier formation and repair.

PMID- 27701447
TI  - Adaptive Path Selection for Link Loss Inference in Network Tomography
      Applications.
AB  - In this study, we address the problem of selecting the optimal end-to-end paths
      for link loss inference in order to improve the performance of network tomography
      applications, which infer the link loss rates from the path loss rates. Measuring
      the path loss rates using end-to-end probing packets may incur additional traffic
      overheads for networks, so it is important to select the minimum path set
      carefully while maximizing their performance. The usual approach is to select the
      maximum independent paths from the candidates simultaneously, while the other
      paths can be replaced by linear combinations of them. However, this approach
      ignores the fact that many paths always exist that do not lose any packets, and
      thus it is easy to determine that all of the links of these paths also have 0
      loss rates. Not considering these good paths will inevitably lead to inefficiency
      and high probing costs. Thus, we propose an adaptive path selection method that
      selects paths sequentially based on the loss rates of previously selected paths.
      We also propose a theorem as well as a graph construction and decomposition
      approach to efficiently find the most valuable path during each round of
      selection. Our new method significantly outperforms the classical path selection
      method based on simulations in terms of the probing cost, number of accurate
      links determined, and the running speed.

PMID- 27701445
TI  - Determinants of the Transmission Variation of Hand, Foot and Mouth Disease in
      China.
AB  - Severe outbreaks of hand, foot and mouth disease (HFMD) have occurred in China
      for decades. Our understanding of the HFMD transmission process and its
      determinants is still limited. In this paper, factors that affect the local
      variation of HFMD transmission process were studied. Three classes of factors,
      including meteorological, demographic and public health intervention factors,
      were carefully selected and their effects on HFMD transmission were investigated
      with Pearson's correlation coefficient and multiple linear regression models. The
      determining factors for the variation of HFMD transmission were different for the
      southeastern and the northwestern regions of China. In the northwest, fadeouts
      occurred yearly, and the average age at infection and the fadeout were negatively
      correlated with the population density. In the southeast, HFMD transmission was
      governed by the combined effects of the birth rate, the relative humidity and the
      interaction of the Health System Performance and the log of the population
      density. When the Health System Performance was low, HFMD transmission increased
      with the population density, but when the Health System Performance was high, the
      better health performance counteracted the transmission increase due to the
      higher population density.

PMID- 27701446
TI  - An Evaluation of Passive and Active Approaches to Improve Tuberculosis
      Notifications in Afghanistan.
AB  - BACKGROUND: In Afghanistan, improving TB case detection remains challenging. In
      2014, only half of the estimated incident TB cases were notified, and
      notifications have decreased since peaking in 2007. Active case finding has been
      increasingly considered to improve TB case notifications. While access to health
      services has improved in Afghanistan, it remains poor and many people seeking
      health services won't receive proper care. METHODS: From October 2011 through
      December 2012 we conducted three separate case finding strategies in six
      provinces of Afghanistan and measured impact on TB case notification.
      Systematically screening cough among attendees at 47 health facilities, active
      household contact investigation of smear-positive index TB patients, and active
      screening at 15 camps for internally displaced people were conducted. We
      collected both intervention yield and official quarterly notification data.
      Additional TB notifications were calculated by comparing numbers of cases
      notified during the intervention with those notified before the intervention,
      then adjusting for secular trends in notification. RESULTS: We screened 2,022,127
      people for TB symptoms during the intervention, tested 59,838 with smear
      microscopy and detected 5,046 people with smear-positive TB. Most cases (81.7%,
      4,125) were identified in health facilities while nearly 20% were found through
      active case finding. A 56% increase in smear-positive TB notifications was
      observed between the baseline and intervention periods among the 47 health
      facilities, where cases detected by all three strategies were notified.
      DISCUSSION: While most people with TB are likely to be identified through health
      facility screening, there are many people who remain without a proper diagnosis
      if outreach is not attempted. This is especially true in places like Afghanistan
      where access to general services is poor. Targeted active case finding can
      improve the number of people who are detected and treated for TB and can push
      towards the targets of the Stop TB Global Plan and End TB Strategy.

PMID- 27701448
TI  - Integrity of the Human Faecal Microbiota following Long-Term Sample Storage.
AB  - In studies of the human microbiome, faecal samples are frequently used as a non
      invasive proxy for the study of the intestinal microbiota. To obtain reliable
      insights, the need for bacterial DNA of high quality and integrity following
      appropriate faecal sample collection and preservation steps is paramount. In a
      study of dietary mineral balance in the context of type 2 diabetes (T2D), faecal
      samples were collected from healthy and T2D individuals throughout a 13-day
      residential trial. These samples were freeze-dried, then stored mostly at -20
      degrees C from the trial date in 2000/2001 until the current research in 2014.
      Given the relative antiquity of these samples (~14 years), we sought to evaluate
      DNA quality and comparability to freshly collected human faecal samples.
      Following the extraction of bacterial DNA, gel electrophoresis indicated that our
      DNA extracts were more sheared than extracts made from freshly collected faecal
      samples, but still of sufficiently high molecular weight to support amplicon
      based studies. Likewise, spectrophotometric assessment of extracts revealed that
      they were of high quality and quantity. A subset of bacterial 16S rRNA gene
      amplicons were sequenced using Illumina MiSeq and compared against publicly
      available sequence data representing a similar cohort analysed by the American
      Gut Project (AGP). Notably, our bacterial community profiles were highly
      consistent with those from the AGP data. Our results suggest that when faecal
      specimens are stored appropriately, the microbial profiles are preserved and
      robust to extended storage periods.

PMID- 27701449
TI  - Bayesian Correlation Analysis for Sequence Count Data.
AB  - Evaluating the similarity of different measured variables is a fundamental task
      of statistics, and a key part of many bioinformatics algorithms. Here we propose
      a Bayesian scheme for estimating the correlation between different entities'
      measurements based on high-throughput sequencing data. These entities could be
      different genes or miRNAs whose expression is measured by RNA-seq, different
      transcription factors or histone marks whose expression is measured by ChIP-seq,
      or even combinations of different types of entities. Our Bayesian formulation
      accounts for both measured signal levels and uncertainty in those levels, due to
      varying sequencing depth in different experiments and to varying absolute levels
      of individual entities, both of which affect the precision of the measurements.
      In comparison with a traditional Pearson correlation analysis, we show that our
      Bayesian correlation analysis retains high correlations when measurement
      confidence is high, but suppresses correlations when measurement confidence is
      low-especially for entities with low signal levels. In addition, we consider the
      influence of priors on the Bayesian correlation estimate. Perhaps surprisingly,
      we show that naive, uniform priors on entities' signal levels can lead to highly
      biased correlation estimates, particularly when different experiments have widely
      varying sequencing depths. However, we propose two alternative priors that
      provably mitigate this problem. We also prove that, like traditional Pearson
      correlation, our Bayesian correlation calculation constitutes a kernel in the
      machine learning sense, and thus can be used as a similarity measure in any
      kernel-based machine learning algorithm. We demonstrate our approach on two RNA
      seq datasets and one miRNA-seq dataset.

PMID- 27701450
TI  - Multivariate Analysis of Anthropometric Traits Using Summary Statistics of Genome
      Wide Association Studies from GIANT Consortium.
AB  - Meta-analysis of single trait for multiple cohorts has been used for increasing
      statistical power in genome-wide association studies (GWASs). Although hundreds
      of variants have been identified by GWAS, these variants only explain a small
      fraction of phenotypic variation. Cross-phenotype association analysis (CPASSOC)
      can further improve statistical power by searching for variants that contribute
      to multiple traits, which is often relevant to pleiotropy. In this study, we
      performed CPASSOC analysis on the summary statistics from the Genetic
      Investigation of ANthropometric Traits (GIANT) consortium using a novel method
      recently developed by our group. Sex-specific meta-analysis data for height, body
      mass index (BMI), and waist-to-hip ratio adjusted for BMI (WHRadjBMI) from
      discovery phase of the GIANT consortium study were combined using CPASSOC for
      each trait as well as 3 traits together. The conventional meta-analysis results
      from the discovery phase data of GIANT consortium studies were used to compare
      with that from CPASSOC analysis. The CPASSOC analysis was able to identify 17
      loci associated with anthropometric traits that were missed by conventional meta
      analysis. Among these loci, 16 have been reported in literature by including
      additional samples and 1 is novel. We also demonstrated that CPASSOC is able to
      detect pleiotropic effects when analyzing multiple traits.

PMID- 27701451
TI  - External Resistances Applied to MFC Affect Core Microbiome and Swine Manure
      Treatment Efficiencies.
AB  - Microbial fuel cells (MFCs) can be designed to combine water treatment with
      concomitant electricity production. Animal manure treatment has been poorly
      explored using MFCs, and its implementation at full-scale primarily relies on the
      bacterial distribution and activity within the treatment cell. This study reports
      the bacterial community changes at four positions within the anode of two almost
      identically operated MFCs fed swine manure. Changes in the microbiome structure
      are described according to the MFC fluid dynamics and the application of a
      maximum power point tracking system (MPPT) compared to a fixed resistance system
      (Ref-MFC). Both external resistance and cell hydrodynamics are thought to heavily
      influence MFC performance. The microbiome was characterised both quantitatively
      (qPCR) and qualitatively (454-pyrosequencing) by targeting bacterial 16S rRNA
      genes. The diversity of the microbial community in the MFC biofilm was reduced
      and differed from the influent swine manure. The adopted electric condition (MPPT
      vs fixed resistance) was more relevant than the fluid dynamics in shaping the MFC
      microbiome. MPPT control positively affected bacterial abundance and promoted the
      selection of putatively exoelectrogenic bacteria in the MFC core microbiome
      (Sedimentibacter sp. and gammaproteobacteria). These differences in the
      microbiome may be responsible for the two-fold increase in power production
      achieved by the MPPT-MFC compared to the Ref-MFC.

PMID- 27701452
TI  - Effects of Bariatric Surgery on Renal Function in Obese Patients: A Systematic
      Review and Meta Analysis.
AB  - BACKGROUND: Obesity is an independent risk factor of development and progression
      of chronic kidney disease (CKD). Data on the benefits of bariatric surgery in
      obese patients with impaired kidney function have been conflicting. OBJECTIVE: To
      explore whether there is improvement in glomerular filtration rate (GFR),
      proteinuria or albuminuria after bariatric surgery. METHODS: We comprehensively
      searched the databases of MEDLINE, Embase, web of science and Cochrane for
      randomized, controlled trials and observational studies that examined bariatric
      surgery in obese subjects with impaired kidney function. Outcomes included the
      pre- and post-bariatric surgery GFR, proteinuria and albuminuria. In obese
      patients with hyperfiltration, we draw conclusions from studies using measured
      GFR (inulin or iothalamate clearance) unadjusted for BSA only. Study quality was
      evaluated using the Newcastle-Ottawa Scale. RESULTS: 32 observational studies met
      our inclusion criteria, and 30 studies were included in the meta-analysis. No
      matter in dichotomous data or in dichotomous data, there were statistically
      significant reduction in hyperfiltration, albuminuria and proteinuria after
      bariatric surgery. LIMITATIONS: The main limitation of this meta-analysis is the
      lack of randomized controlled trials (RCTs). Another limitation is the lack of
      long-term follow-up. CONCLUSIONS: Bariatric surgery could prevent further decline
      in renal function by reducing proteinuria, albuminuria and improving glomerular
      hyperfiltration in obese patients with impaired renal function. However, whether
      bariatric surgery reverses CKD or delays ESRD progression is still in question,
      large, randomized prospective studies with a longer follow-up are needed.

PMID- 27701453
TI  - Plasma Pentosidine and Its Association with Mortality in Patients with Chronic
      Kidney Disease.
AB  - BACKGROUND: Circulating advanced glycated end-products (AGEs) including
      pentosidine accumulating in chronic kidney disease (CKD) patients due to
      retention and increased formation are thought to contribute to cardiovascular
      disease (CVD). Here we evaluated factors linked to increased plasma pentosidine
      and its association with mortality in patients with different stages of CKD and
      undergoing different treatments. METHODS: Plasma pentosidine, biomarkers of
      inflammation, oxidative stress and nutritional status were investigated in CKD 1
      2 (n = 37), CKD 3-4 (n = 54), CKD 5 non-dialyzed (CKD5-ND; n = 386), peritoneal
      dialysis (PD; n = 74) and hemodialysis (HD; n = 195) patients. Factors predicting
      plasma pentosidine were analysed by multivariate regression analysis and
      mortality risk was assessed by GENMOD procedure. RESULTS: Plasma pentosidine
      levels, which were higher in CKD5-ND, PD and HD groups than in CKD 1-2 group,
      were significantly lower in PD than in HD patients, and not different between PD
      patients and CKD5-ND patients. Pentosidine associated inversely with glomerular
      filtration rate (GFR), and additionally in PD with 8-hydroxy-2'-deoxyguanosine (8
      OHdG), and interleukin 6 (IL-6); in HD with age, IL-6 and body mass index (BMI);
      in CKD5-ND with age, 8-OHdG, IL-6, high-sensitive C-reactive protein (hsCRP), and
      soluble vascular cell adhesion protein-1 (sVCAM-1); in CKD 3-4 with 8-OHdG and
      sVCAM-1; and in CKD 1-2 with age and sVCAM-1. In multivariate analysis, age (one
      standard deviation, 1-SD higher), malnutrition (subjective global assessment,
      SGA), oxidative stress (8-OHdG, 1-SD higher), and belonging to CKD5-ND, HD and PD
      cohorts associated with 1-SD higher pentosidine. In GENMOD, 1-SD higher
      pentosidine independently predicted all-cause mortality (relative risk, RR =
      1.04; 95% confidence interval, CI, 1.01-1.08, p = 0.01) and CVD mortality (RR =
      1.03; 95% CI, 1.01-1.06, p = 0.03) after adjusting for all confounders.
      CONCLUSIONS: Plasma pentosidine is markedly elevated in CKD and associates with
      low GFR, oxidative stress and inflammation, and is an independent predictor of
      mortality in CKD patients.

PMID- 27701454
TI  - Microbiota of the Small Intestine Is Selectively Engulfed by Phagocytes of the
      Lamina Propria and Peyer's Patches.
AB  - Phagocytes such as dendritic cells and macrophages, which are distributed in the
      small intestinal mucosa, play a crucial role in maintaining mucosal homeostasis
      by sampling the luminal gut microbiota. However, there is limited information
      regarding microbial uptake in a steady state. We investigated the composition of
      murine gut microbiota that is engulfed by phagocytes of specific subsets in the
      small intestinal lamina propria (SILP) and Peyer's patches (PP). Analysis of
      bacterial 16S rRNA gene amplicon sequences revealed that: 1) all the phagocyte
      subsets in the SILP primarily engulfed Lactobacillus (the most abundant microbe
      in the small intestine), whereas CD11bhi and CD11bhiCD11chi cell subsets in PP
      mostly engulfed segmented filamentous bacteria (indigenous bacteria in rodents
      that are reported to adhere to intestinal epithelial cells); and 2) among the
      Lactobacillus species engulfed by the SILP cell subsets, L. murinus was engulfed
      more frequently than L. taiwanensis, although both these Lactobacillus species
      were abundant in the small intestine under physiological conditions. These
      results suggest that small intestinal microbiota is selectively engulfed by
      phagocytes that localize in the adjacent intestinal mucosa in a steady state.
      These observations may provide insight into the crucial role of phagocytes in
      immune surveillance of the small intestinal mucosa.

PMID- 27701456
TI  - Robust and Efficient Frequency Estimator for Undersampled Waveforms Based on
      Frequency Offset Recognition.
AB  - This paper proposes an efficient frequency estimator based on Chinese Remainder
      Theorem for undersampled waveforms. Due to the emphasis on frequency offset
      recognition (i.e., frequency shift and compensation) of small-point DFT
      remainders, compared to estimators using large-point DFT remainders, it can
      achieve higher noise robustness in low signal-to-noise ratio (SNR) cases and
      higher accuracy in high SNR cases. Numerical results show that, by incorporating
      a remainder screening method and the Tsui spectrum corrector, the proposed
      estimator not only lowers the SNR threshold of detection, but also provides a
      higher accuracy than the large-point DFT estimator when the DFT size decreases to
      1/90 of the latter case.

PMID- 27701455
TI  - Regulation of HBEGF by Micro-RNA for Survival of Developing Human Trophoblast
      Cells.
AB  - INTRODUCTION: The growth factor HBEGF is upregulated post-transcriptionally in
      the low O2 environment of the human placenta during the first 10 weeks of
      pregnancy. We have examined the possible roles of HBEGF turnover and micro-RNA
      (miRNA) in its regulation by O2 in human first trimester trophoblast. METHODS:
      HTR-8/SVneo trophoblast cells were cultured at 2% or 20% O2. The cells were
      transfected with a dual luciferase reporter construct (psiCHECK-2) containing no
      insert (control), the HBEGF 3' untranslated region (3'UTR), or sub-regions of the
      3'UTR, as well as with siRNA for DGCR8. RNA was extracted from trophoblast cells
      cultured at 2% O2 for 0-4 h for next-generation sequencing. HBEGF was quantified
      by ELISA. HBEGF, DGCR8, and beta-actin were examined by western blotting.
      RESULTS: Protein turnover studies, using 10 MUg/ml cyclohexamide, 1 MUg/ml
      lactocystin, or 100 MUg/ml MG132, demonstrated faster HBEGF degradation at 20% O2
      than 2% O2, mediated by the proteasome. However, proteasome inhibition failed to
      initiate HBEGF accumulation at 20% O2. Reporter assays, comparing to empty
      vector, demonstrated that the intact HBEGF 3' UTR inhibited expression (0.26),
      while fragments containing only its flanking regions increased reporter activity
      (3.15; 3.43). No differential expression of miRNAs was found in trophoblast cells
      cultured at 2% and 20% O2. Nevertheless, HBEGF upregulation at 2% O2 was blocked
      when the miRNA-processing protein DGCR8 was silenced, suggesting a role for
      miRNA. CONCLUSION: Our findings suggest involvement of flanking regions of the
      3'UTR in activating HBEGF protein synthesis in response to 2% O2, possibly
      through a miRNA-mediated mechanism.

PMID- 27701457
TI  - Distress Propagation in Complex Networks: The Case of Non-Linear DebtRank.
AB  - We consider a dynamical model of distress propagation on complex networks, which
      we apply to the study of financial contagion in networks of banks connected to
      each other by direct exposures. The model that we consider is an extension of the
      DebtRank algorithm, recently introduced in the literature. The mechanics of
      distress propagation is very simple: When a bank suffers a loss, distress
      propagates to its creditors, who in turn suffer losses, and so on. The original
      DebtRank assumes that losses are propagated linearly between connected banks.
      Here we relax this assumption and introduce a one-parameter family of non-linear
      propagation functions. As a case study, we apply this algorithm to a data-set of
      183 European banks, and we study how the stability of the system depends on the
      non-linearity parameter under different stress-test scenarios. We find that the
      system is characterized by a transition between a regime where small shocks can
      be amplified and a regime where shocks do not propagate, and that the overall
      stability of the system increases between 2008 and 2013.

PMID- 27701458
TI  - A Precise Annotation of Phase-Amplitude Coupling Intensity.
AB  - Neuronal information can be coded in different temporal and spatial scales. Cross
      frequency coupling of neuronal oscillations, especially phase-amplitude coupling
      (PAC), plays a critical functional role in neuronal communication and large scale
      neuronal encoding. Several approaches have been developed to assess PAC
      intensity. It is generally agreed that the PAC intensity relates to the uneven
      distribution of the fast oscillation amplitude conditioned on the slow
      oscillation phase. However, it is still not clear what the PAC intensity exactly
      means. In the present study, it was found that there were three types of
      interferential signals taking part in PAC phenomenon. Based on the classification
      of interferential signals, the conception of PAC intensity is theoretically
      annotated as the proportion of slow or fast oscillation that is involved in a
      related PAC phenomenon. In order to make sure that the annotation is proper to
      some content, simulation data are constructed and then analyzed by three PAC
      approaches. These approaches are the mean vector length (MVL), the modulation
      index (MI), and a new permutation mutual information (PMI) method in which the
      permutation entropy and the information theory are applied. Results show positive
      correlations between PAC values derived from all three methods and the suggested
      intensity. Finally, the amplitude distributions, i.e. the phase-amplitude plots,
      obtained from different PAC intensities show that the annotation proposed in the
      study is in line with the previous understandings.

PMID- 27701459
TI  - Monoclonal Antibodies 13A4 and AC133 Do Not Recognize the Canine Ortholog of
      Mouse and Human Stem Cell Antigen Prominin-1 (CD133).
AB  - The pentaspan membrane glycoprotein prominin-1 (CD133) is widely used in medicine
      as a cell surface marker of stem and cancer stem cells. It has opened new avenues
      in stem cell-based regenerative therapy and oncology. This molecule is largely
      used with human samples or the mouse model, and consequently most biological
      tools including antibodies are directed against human and murine prominin-1.
      Although the general structure of prominin-1 including its membrane topology is
      conserved throughout the animal kingdom, its primary sequence is poorly
      conserved. Thus, it is unclear if anti-human and -mouse prominin-1 antibodies
      cross-react with their orthologs in other species, especially dog. Answering this
      issue is imperative in light of the growing number of studies using canine
      prominin-1 as an antigenic marker. Here, we address this issue by cloning the
      canine prominin-1 and use its overexpression as a green fluorescent protein
      fusion protein in Madin-Darby canine kidney cells to determine its
      immunoreactivity with antibodies against human or mouse prominin-1. We used
      immunocytochemistry, flow cytometry and immunoblotting techniques and
      surprisingly found no cross-species immunoreactivity. These results raise some
      caution in data interpretation when anti-prominin-1 antibodies are used in
      interspecies studies.

PMID- 27701460
TI  - The Replicative Consequences of Papillomavirus E2 Protein Binding to the Origin
      Replication Factor ORC2.
AB  - The origin recognition complex (ORC) coordinates a series of events that lead to
      initiation of DNA strand duplication. As a nuclear double stranded DNA plasmid,
      the papillomavirus (PV) genome resembles a mini-chromosome in infected cells. To
      initiate its replication, the viral E2 protein binds to and recruits the E1 DNA
      helicase at the viral origin. PV genome replication program exhibits three
      stages: initial amplification from a single genome upon infection to a few copies
      per cell, a cell cycle linked maintenance phase, and a differentiation dependent
      late stage where the genome is amplified to thousands of copies. Involvement of
      ORC or other pre-replication complex (pre-RC) factors has not been described. We
      report that human PV (HPV) and bovine PV (BPV-1) E2 proteins bind to ORC2,
      however, ORC2 was not detected at the viral origin. Depletion of ORC2 enhanced PV
      replication in a transient replication model and in keratinocytes stably
      maintaining viral episomes, while there was no effect on copy number in a cell
      line with integrated HPV genomes. Consistent with this, occupancy of E1 and E2 at
      the viral origin increased following ORC2 silencing. These data imply that ORC2
      is not necessary for activation of the PV origin by E1 and E2 but instead
      suppresses E2 replicative function. Furthermore, we observed that over-expression
      of HPV E2 decreased ORC2 occupation at two known mammalian origins of
      replication, suggesting that E2 restricts pre-ORC assembly that could otherwise
      compete for host replication complexes necessary for viral genome amplification.
      We infer that the ORC2 complex with E2 restricts viral replication in the
      maintenance phase of the viral replication program and that elevated levels of E2
      that occur during the differentiation dependent amplification stage subvert ORC
      loading and hence DNA synthesis at cellular origins.

PMID- 27701461
TI  - MUC18 Regulates Lung Rhinovirus Infection and Inflammation.
AB  - BACKGROUND: MUC18 is upregulated in the lungs of asthma and COPD patients. It has
      been shown to have pro-inflammatory functions in cultured human airway epithelial
      cells during viral infections and in mice during lung bacterial infections.
      However, the in vivo role of MUC18 in the context of viral infections remains
      poorly understood. The goal of this study is to define the in vivo function of
      MUC18 during respiratory rhinovirus infection. METHODS: Muc18 wild-type (WT) and
      knockout (KO) mice were infected with human rhinovirus 1B (HRV-1B) and sacrificed
      after 1 day to determine the inflammatory and antiviral responses. To examine the
      direct effects of Muc18 on viral infection, tracheal epithelial cells isolated
      from WT and KO mice were grown under air-liquid interface and infected with HRV
      1B. Finally, siRNA mediated knockdown of MUC18 was performed in human airway
      epithelial cells (AECs) to define the impact of MUC18 on human airway response to
      HRV-1B. RESULTS: Both viral load and neutrophilic inflammation were significantly
      decreased in Muc18 KO mice compared to WT mice. In the in vitro setting, viral
      load was significantly lower and antiviral gene expression was higher in airway
      epithelial cells of Muc18 KO mice than the WT mice. Furthermore, in MUC18
      knockdown human AECs, viral load was decreased and antiviral gene expression was
      increased compared to controls. CONCLUSIONS: Our study is the first to
      demonstrate MUC18's pro-inflammatory and pro-viral function in an in vivo mouse
      model of rhinovirus infection.

PMID- 27701462
TI  - Accuracy of a Real-Time, Computerized, Binocular, Three-Dimensional Trajectory
      Tracking Device for Recording Functional Mandibular Movements.
AB  - OBJECTIVE: Developments in digital technology have permitted researchers to study
      mandibular movements. Here, the accuracy of a real-time, computerized, binocular,
      three-dimensional (3D) trajectory-tracking device for recording functional
      mandibular movements was evaluated. METHODS: An occlusal splint without the
      occlusal region was created based on a plaster cast of the lower dentition. The
      splint was rigidly connected with a target on its labial side and seated on the
      cast. The cast was then rigidly attached to the stage of a high-precision
      triaxial electronic translator, which was used to move the target-cast-stage
      complex. Half-circular movements (5.00-mm radius) in three planes (XOY, XOZ, YOZ)
      and linear movements along the x-axis were performed at 5.00 mm/s. All trajectory
      points were recorded with the binocular 3D trajectory-tracking device and fitted
      to arcs or lines, respectively, with the Imageware software. To analyze the
      accuracy of the trajectory-tracking device, the mean distances between the
      trajectory points and the fitted arcs or lines were measured, and the mean
      differences between the lengths of the fitted arcs' radii and a set value (5.00
      mm) were then calculated. A one-way analysis of variance was used to evaluate the
      spatial consistency of the recording accuracy in three different planes. RESULTS:
      The mean distances between the trajectory points and fitted arcs or lines were
      0.076 +/- 0.033 mm or 0.089 +/- 0.014 mm. The mean difference between the lengths
      of the fitted arcs' radii and the set value (5.00 mm) was 0.025 +/- 0.071 mm. A
      one-way ANOVA showed that the recording errors in three different planes were not
      statistically significant. CONCLUSION: These results suggest that the device can
      record certain movements at 5.00 mm/s, which is similar to the speed of
      functional mandibular movements. In addition, the recordings had an error of <0.1
      mm and good spatial consistency. Thus, the device meets some of the requirements
      necessary for recording human mandibular movements.

PMID- 27701463
TI  - Low-Grade Inflammation Is Associated with Susceptibility to Infection in Healthy
      Men: Results from the Danish Blood Donor Study (DBDS).
AB  - INTRODUCTION: The aim of this study was to examine whether low-grade inflammation
      (LGI) is associated with a subsequently increased risk of infection. METHODS: We
      included 15,754 healthy participants from the Danish Blood Donor Study, who
      completed a questionnaire on health-related items. LGI was defined as a C
      reactive protein level between 3 and 10 mg/L. Infections were identified by ICD
      10 codes in the Danish National Patient Register and ATC-codes in the Danish
      Prescription Register. Multivariable Cox proportional hazard analysis was used as
      the statistical model. RESULTS: During 53,302 person-years of observation, 571
      participants were hospitalized for infection. Similarly, during 26,125 person
      years of observation, 7,276 participants filled a prescription of antimicrobials.
      LGI was associated with increased risk of hospital-based treatment for infection
      only among men (hazard ratio = 1.60, 95% confidence interval (CI): 1.10-2.34) and
      specifically infections were abscesses and infections of the skin and
      subcutaneous tissue. Similarly, LGI was associated with the overall use of
      antimicrobials among men, and particularly with phenoxymethylpenicillin and broad
      spectrum antimicrobials for treatment of urinary tract infections. The difference
      between men and women was not statistically significant. CONCLUSIONS: In a large
      cohort of healthy individuals, LGI was associated with an increased risk of
      infection among healthy male blood donors.

PMID- 27701464
TI  - The Positron Emission Tomography Tracer 3'-Deoxy-3'-[18F]Fluorothymidine
      ([18F]FLT) Is Not Suitable to Detect Tissue Proliferation Induced by Systemic
      Yersinia enterocolitica Infection in Mice.
AB  - Most frequently, gram-negative bacterial infections in humans are caused by
      Enterobacteriaceae and remain a major challenge in medical diagnostics. We non
      invasively imaged moderate and severe systemic Yersinia enterocolitica infections
      in mice using the positron emission tomography (PET) tracer 3'-deoxy-3'
      [18F]fluorothymidine ([18F]FLT), which is a marker of proliferation, and compared
      the in vivo results to the ex vivo biodistributions, bacterial loads, and
      histologies of the corresponding organs. Y. enterocolitica infection is
      detectable with histology using H&E staining and immunohistochemistry for Ki 67.
      [18F]FLT revealed only background uptake in the spleen, which is the main
      manifestation site of systemic Y. enterocolitica-infected mice. The uptake was
      independent of the infection dose. Antibody-based thymidine kinase 1 (Tk-1)
      staining confirmed the negative [18F]FLT-PET data. Histological alterations of
      spleen tissue, observed via Ki 67-antibody-based staining, can not be detected by
      [18F]FLT-PET in this model. Thus, the proliferation marker [18F]FLT is not a
      suitable tracer for the diagnosis of systemic Y. enterocolitica infection in the
      C57BL/6 animal model of yersiniosis.

PMID- 27701465
TI  - MicroRNA-20b (miR-20b) Promotes the Proliferation, Migration, Invasion, and
      Tumorigenicity in Esophageal Cancer Cells via the Regulation of Phosphatase and
      Tensin Homologue Expression.
AB  - Increasing evidence has indicated that many microRNAs participate in the
      development and progression of esophageal cancer and gene expression regulation.
      MicroRNA-20b (miR-20b) has been reported to be aberrantly expressed in various
      cancers, but its exact role in esophageal cancer cells remains unclear so far.
      Therefore, we detected the levels of miR-20b in esophageal tumor tissues and
      their adjacent normal tissues, and various esophageal cancer cell lines by qRT
      PCR. We also explored the effects of miR-20b on cell proliferation, migration,
      invasion and tumorigenicity of esophageal carcinoma cells through transfection
      with miR-20b mimics or inhibitor to upregulate or downregulate miR-20b expression
      in the esophageal cancer cells Eca-109 and KYSE-150, respectively. Additionally,
      the 3'-untranslated region (3'-UTR) of phosphatase and tensin homologue (PTEN)
      binding with miR-20b was analyzed by dual-luciferase reporter assays. The results
      indicated that miR-20b expression level in esophageal tumor tissues was
      significantly increased compared with their neighboring normal tissues, but its
      expression was inverse with PTEN protein expression. Luciferase assays confirmed
      that the 3'-UTR of PTEN was a target of miR-20b in esophageal cancer cells. MiR
      20b upregulation promoted cell proliferation, migration, invasiveness, and tumor
      growth, and decreased apoptosis, and reduced PTEN protein level but not mRNA
      expression in Eca-109 cells. Conversely, downregulation of miR-20b suppressed
      these processes in KYSE-150 cells, and enhanced PTEN protein expression. These
      data indicate that miR-20b plays important roles in tumorigenesis of esophageal
      cancer possibly via regulation of PTEN expression, and it may be a potential
      therapeutic target for esophageal cancer treatment.

PMID- 27701466
TI  - Use of the 'Accountability for Reasonableness' Approach to Improve Fairness in
      Accessing Dialysis in a Middle-Income Country.
AB  - Universal access to renal replacement therapy is beyond the economic capability
      of most low and middle-income countries due to large patient numbers and the high
      recurrent cost of treating end stage kidney disease. In countries where limited
      access is available, no systems exist that allow for optimal use of the scarce
      dialysis facilities. We previously reported that using national guidelines to
      select patients for renal replacement therapy resulted in biased allocation. We
      reengineered selection guidelines using the 'Accountability for Reasonableness'
      (procedural fairness) framework in collaboration with relevant stakeholders,
      applying these in a novel way to categorize and prioritize patients in a unique
      hierarchical fashion. The guidelines were primarily premised on patients being
      transplantable. We examined whether the revised guidelines enhanced fairness of
      dialysis resource allocation. This is a descriptive study of 1101 end stage
      kidney failure patients presenting to a tertiary renal unit in a middle-income
      country, evaluated for dialysis treatment over a seven-year period. The
      Assessment Committee used the accountability for reasonableness-based guidelines
      to allocate patients to one of three assessment groups. Category 1 patients were
      guaranteed renal replacement therapy, Category 3 patients were palliated, and
      Category 2 were offered treatment if resources allowed. Only 25.2% of all end
      stage kidney disease patients assessed were accepted for renal replacement
      treatment. The majority of patients (48%) were allocated to Category 2. Of 134
      Category 1 patients, 98% were accepted for treatment while 438 (99.5%) Category 3
      patients were excluded. Compared with those palliated, patients accepted for
      dialysis treatment were almost 10 years younger, employed, married with children
      and not diabetic. Compared with our previous selection process our current method
      of priority setting based on procedural fairness arguably resulted in more
      equitable allocation of treatment but, more importantly, it is a model that is
      morally, legally and ethically more defensible.

PMID- 27701467
TI  - Germline Variants of Prostate Cancer in Japanese Families.
AB  - Prostate cancer (PC) is the second most common cancer in men. Family history is
      the major risk factor for PC. Only two susceptibility genes were identified in
      PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients
      with PC has not been reported in Japanese families. In this study, we conducted
      exome sequencing followed by Sanger sequencing to explore responsible germline
      variants in 140 Japanese patients with PC from 66 families. In addition to known
      susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a
      mutually exclusive manner in seven large PC families (three or four patients per
      family). We also found shared variants of BRCA2, HOXB13, and TRRAP from 59
      additional small PC families (two patients per family). We identified two
      deleterious HOXB13 variants (F127C and G132E). Further exploration of the shared
      variants in rest of the families revealed deleterious variants of the so-called
      cancer genes (ATP1A1, BRIP1, FANCA, FGFR3, FLT3, HOXD11, MUTYH, PDGFRA, SMARCA4,
      and TCF3). The germline variant profile provides a new insight to clarify the
      genetic etiology and heterogeneity of PC among Japanese men.

PMID- 27701468
TI  - Determinants of Left Atrial Volume in Patients with Atrial Fibrillation.
AB  - INTRODUCTION: Left atrial (LA) enlargement is an important risk factor for
      incident stroke and a key determinant for the success of rhythm control
      strategies in patients with atrial fibrillation (AF). However, factors associated
      with LA volume in AF patients remain poorly understood. METHODS: Patients with
      paroxysmal or persistent AF were enrolled in this study. Real time 3-D
      echocardiography was performed in all participants and analyzed offline in a
      standardized manner. We performed stepwise backward linear regression analyses
      using a broad set of clinical parameters to determine independent correlates for
      3-D LA volume. RESULTS: We included 210 patients (70.9% male, mean age 61+/
      11years). Paroxysmal and persistent AF were present in 95 (45%) and 115 (55%)
      patients, respectively. Overall, 115 (55%) had hypertension, 11 (5%) had
      diabetes, and 18 (9%) had ischemic heart disease. Mean indexed LA volume was 36+/
      12ml/m2. In multivariable models, significant associations were found for female
      sex (beta coefficient -10.51 (95% confidence interval (CI) -17.85;-3.16), p =
      0.0053), undergoing cardioversion (beta 11.95 (CI 5.15; 18.74), p = 0.0006),
      diabetes (beta 14.23 (CI 2.36; 26.10), p = 0.019), body surface area (BSA) (beta
      34.21 (CI 19.30; 49.12), p<0.0001), glomerular filtration rate (beta -0.21 (CI 
      0.36; -0.06), p = 0.0064) and plasma levels of NT-pro brain natriuretic peptide
      (NT-proBNP) (beta 6.79 (CI 4.05; 9.52), p<0.0001), but not age (p = 0.59) or
      hypertension (p = 0.42). Our final model explained 52% of the LA volume
      variability. CONCLUSIONS: In patients with AF, the most important correlates with
      LA volume are sex, BSA, diabetes, renal function and NT-proBNP, but not age or
      hypertension. These results may help to refine rhythm control strategies in AF
      patients.

PMID- 27701469
TI  - Impact of TNF-alpha (rs1800629) and IL-6 (rs1800795) Polymorphisms on Cognitive
      Impairment in Asian Breast Cancer Patients.
AB  - OBJECTIVE: Expression of pro-inflammatory cytokines is influenced by single
      nucleotide polymorphisms (SNPs) in the promoter regions of the pro-inflammatory
      cytokine genes, and cytokines are associated with the occurrence of post
      chemotherapy cognitive impairment. Hence, the aim of this study was to evaluate
      the associations between two common pro-inflammatory cytokine gene polymorphisms
      namely, IL6-174 (rs1800795 G>C) and TNF-308 (rs1800629 G>A), and chemotherapy
      associated cognitive impairment (CACI) among Asian early-stage breast cancer
      patients. In addition, the differential effect of these SNPs on plasma IL-6 and
      TNF-alpha levels, and the associations of plasma IL-6 and TNF-alpha levels with
      CACI were also assessed. METHODS: Asian early-stage breast cancer patients (Stage
      I to III) receiving chemotherapy were prospectively recruited from two cancer
      centers in Singapore. Patients' cognitive function was longitudinally assessed
      using the validated FACT-Cog (ver. 3) and an objective computerized battery,
      HeadminderTM at three-time points. Plasma IL-6 and TNF-alpha levels were analyzed
      using the multiplex immunoassay, and genotyping was performed using Sanger
      sequencing. Regression analyses and generalized estimating equation were utilized
      for statistical analysis. RESULTS: A total of 125 patients were included (mean
      age: 50.3; Chinese: 80.8%; post-menopausal: 48.0%; 68.0% received anthracycline
      based chemotherapy). 36.8% patients experienced self-perceived cognitive
      impairment, detected in memory (32.8%) and attention (34.2%) domains. Patients
      with higher levels of anxiety (p<0.001) and insomnia (p = 0.003) also reported
      more self-perceived cognitive impairment. Higher plasma concentrations of IL-6
      were associated with greater severity of self-perceived cognitive impairment (p =
      0.001). Polymorphisms of cytokine genes were not associated with expression of
      plasma cytokines. CONCLUSION: Present findings further contribute to the growing
      evidence that supports the role of the pro-inflammatory cytokine IL-6 in the
      occurrence of cognitive impairment post-chemotherapy. However, genetic
      polymorphism of these cytokines did not play a major role to the cytokine
      fluctuations as well as cognitive impairment in this cohort. With an increasing
      evidence to support the cytokine hypothesis, future studies should investigate
      the role of anti-inflammatory agents in mitigating the cognitive impairment
      associated with chemotherapy.

PMID- 27701470
TI  - Neuronal Splicing Regulator RBFOX3 (NeuN) Regulates Adult Hippocampal
      Neurogenesis and Synaptogenesis.
AB  - Dysfunction of RBFOX3 has been identified in neurodevelopmental disorders such as
      autism spectrum disorder, cognitive impairments and epilepsy and a causal
      relationship with these diseases has been previously demonstrated with Rbfox3
      homozygous knockout mice. Despite the importance of RBFOX3 during
      neurodevelopment, the function of RBFOX3 regarding neurogenesis and
      synaptogenesis remains unclear. To address this critical question, we profiled
      the developmental expression pattern of Rbfox3 in the brain of wild-type mice and
      analyzed brain volume, disease-relevant behaviors, neurogenesis, synaptic
      plasticity, and synaptogenesis in Rbfox3 homozygous knockout mice and their
      corresponding wild-type counterparts. Here we report that expression of Rbfox3
      differs developmentally for distinct brain regions. Moreover, Rbfox3 homozygous
      knockout mice exhibited cold hyperalgesia and impaired cognitive abilities.
      Focusing on hippocampal phenotypes, we found Rbfox3 homozygous knockout mice
      displayed deficits in neurogenesis, which was correlated with cognitive
      impairments. Furthermore, RBFOX3 regulates the exons of genes with synapse
      related function. Synaptic plasticity and density, which are related to cognitive
      behaviors, were altered in the hippocampal dentate gyrus of Rbfox3 homozygous
      knockout mice; synaptic plasticity decreased and the density of synapses
      increased. Taken together, our results demonstrate the important role of RBFOX3
      during neural development and maturation. In addition, abnormalities in synaptic
      structure and function occur in Rbfox3 homozygous knockout mice. Our findings may
      offer mechanistic explanations for human brain diseases associated with
      dysfunctional RBFOX3.

PMID- 27701472
TI  - Correction: CD73 Expressed on gammadelta T Cells Shapes Their Regulatory Effect
      in Experimental Autoimmune Uveitis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0150078.].

PMID- 27701471
TI  - Readability and Content Assessment of Informed Consent Forms for Phase II-IV
      Clinical Trials in China.
AB  - PURPOSE: To explore the readability and content integrity of informed consent
      forms (ICFs) used in China and to compare the quality of Chinese local ICFs with
      that of international ICFs. METHODS: The length, readability and content of 155
      consent documents from phase II-IV drug clinical trials from the Third Xiangya
      Hospital Ethics Committee from November 2009 to January 2015 were evaluated.
      Reading difficulty was tested using a readability formula adapted for the Chinese
      language. An ICF checklist containing 27 required elements was successfully
      constructed to evaluate content integrity. The description of alternatives to
      participation was assessed. The quality of ICFs from different sponsorships were
      also compared. RESULTS: Among the 155 evaluable trials, the ICFs had a median
      length of 5286 words, corresponding to 7 pages. The median readability score was
      4.31 (4.02-4.41), with 63.9% at the 2nd level and 36.1% at the 3rd level. Five of
      the 27 elements were frequently neglected. The average score for the description
      of alternatives to participation was 1.06, and 27.7% of the ICFs did not mention
      any alternatives. Compared with Chinese local ICFs, international ICFs were
      longer, more readable and contained more of the required elements (P < 0.05).
      CONCLUSION: The ICFs used in China were difficult to read for most participants.
      These forms had poor description of alternatives to participation, and failed to
      provide a high degree of information disclosure, including an explanation of
      informed consent, follow-up processing of the data/sample, inclusion/exclusion
      criteria, double blinding, and unpredictable risks. International ICFs had better
      readability and content integrity than Chinese local ICFs. More efforts should
      thus be made to improve the quality of consent documents in China.

PMID- 27701473
TI  - Flagellin FliC Phosphorylation Affects Type 2 Protease Secretion and Biofilm
      Dispersal in Pseudomonas aeruginosa PAO1.
AB  - Protein phosphorylation has a major role in controlling the life-cycle and
      infection stages of bacteria. Proteome-wide occurrence of S/T/Y phosphorylation
      has been reported for many prokaryotic systems. Previously, we reported the
      phosphoproteome of Pseudomonas aeruginosa and Pseudomonas putida. In this study,
      we show the role of S/T phosphorylation of one motility protein, FliC, in
      regulating multiple surface-associated phenomena of P. aeruginosa PAO1. This is
      the first report of occurrence of phosphorylation in the flagellar protein,
      flagellin FliC in its highly conserved N-terminal NDO domain across several Gram
      negative bacteria. This phosphorylation is likely a well-regulated phenomenon as
      it is growth phase dependent in planktonic cells. The absence of phosphorylation
      in the conserved T27 and S28 residues of FliC, interestingly, did not affect
      swimming motility, but affected the secretome of type 2 secretion system (T2SS)
      and biofilm formation of PAO1. FliC phosphomutants had increased levels and
      activities of type 2 secretome proteins. The secretion efficiency of T2SS
      machinery is associated with flagellin phosphorylation. FliC phosphomutants also
      formed reduced biofilms at 24 h under static conditions and had delayed biofilm
      dispersal under dynamic flow conditions, respectively. The levels of type 2
      secretome and biofilm formation under static conditions had an inverse
      correlation. Hence, increase in type 2 secretome levels was accompanied by
      reduced biofilm formation in the FliC phosphomutants. As T2SS is involved in
      nutrient acquisition and biofilm dispersal during survival and spread of P.
      aeruginosa, we propose that FliC phosphorylation has a role in ecological
      adaptation of this opportunistic environmental pathogen. Altogether, we found a
      system of phosphorylation that affects key surface related processes such as
      proteases secretion by T2SS, biofilm formation and dispersal.

PMID- 27701474
TI  - Staphylococcus aureus Tissue Infection During Sepsis Is Supported by Differential
      Use of Bacterial or Host-Derived Lipoic Acid.
AB  - To thrive in diverse environments, bacteria must shift their metabolic output in
      response to nutrient bioavailability. In many bacterial species, such changes in
      metabolic flux depend upon lipoic acid, a cofactor required for the activity of
      enzyme complexes involved in glycolysis, the citric acid cycle, glycine
      catabolism, and branched chain fatty acid biosynthesis. The requirement of lipoic
      acid for metabolic enzyme activity necessitates that bacteria synthesize the
      cofactor and/or scavenge it from environmental sources. Although use of lipoic
      acid is a conserved phenomenon, the mechanisms behind its biosynthesis and
      salvage can differ considerably between bacterial species. Furthermore, low
      levels of circulating free lipoic acid in mammals underscore the importance of
      lipoic acid acquisition for pathogenic microbes during infection. In this study,
      we used a genetic approach to characterize the mechanisms of lipoic acid
      biosynthesis and salvage in the bacterial pathogen Staphylococcus aureus and
      evaluated the requirements for both pathways during murine sepsis. We determined
      that S. aureus lipoic acid biosynthesis and salvage genes exist in an arrangement
      that directly links redox stress response and acetate biosynthesis genes. In
      addition, we found that lipoic acid salvage is dictated by two ligases that
      facilitate growth and lipoylation in distinct environmental conditions in vitro,
      but that are fully compensatory for survival in vivo. Upon infection of mice, we
      found that de novo biosynthesis or salvage promotes S. aureus survival in a
      manner that depends upon the infectious site. In addition, when both lipoic acid
      biosynthesis and salvage are blocked S. aureus is rendered avirulent, implying an
      inability to induce lipoic acid-independent metabolic programs to promote
      survival. Together, our results define the major pathways of lipoic acid
      biosynthesis and salvage in S. aureus and support the notion that bacterial
      nutrient acquisition schemes are instrumental in dictating pathogen proclivity
      for an infectious niche.

PMID- 27701480
TI  - Factors associated with early mortality in haemodialysis patients undergoing
      coronary artery bypass surgery.
AB  - INTRODUCTION: Coronary artery bypass grafting (CABG) results in higher morbidity
      and mortality rates in end-stage renal disease (ESRD) patient populations than in
      patients with normal renal function. This study aimed to identify the early
      results of CABG performed on ESRD patients, and the factors that affected the
      mortality rates of those patients. METHODS: A retrospective evaluation of our
      hospital database revealed 84 haemodialysis-receiving patients who underwent CABG
      during the years 2006 to 2012. Mortality was observed in 21 patients (group 1),
      and this group was compared with the remaining patients (group 2) for peri
      operative parameters such as age, EuroSCORE, functional capacity, myocardial
      infarction, use of inotropes and completeness of revascularisation. RESULTS: The
      study included 60 male (71.4%) and 24 female patients (28.6%); the participants'
      mean age was 59.50 +/- 9.93 years. The pre-operative additive EuroSCORE was 7.96
      +/- 2.88 (range: 2-18). Pre-operative functional capacity was impaired in 35.7%
      of the patients [New York Heart Association (NYHA) classes III-IV]. Mean age and
      preoperative EuroSCORE values of group 1 were significantly higher than those of
      group 2. Impaired functional capacity (NHYA classes III-IV) was also associated
      with mortality (OR: 3.333; 95% CI: 1.199-9.268). Fifty-four patients (64.3%)
      underwent on-pump CABG procedures, and 30 (35.7%) underwent off-pump CABG
      procedures. The study found no statistically significant difference in mortality
      rates between these two techniques. Mortality occurred in 12 patients (22.2%) in
      the on-pump group and in nine (30%) in the off-pump group. Complete
      revascularisation was performed on 46 patients (85.2%) in the on-pump group and
      seven (23.3%) in the off-pump group (p < 0.001). CONCLUSION: Advanced age,
      impaired NYHA functional capacity and pre-operative hypertension were
      determinative for early-term surgical mortality. An on-pump surgical technique is
      recommended to ensure completeness of revascularisation.

PMID- 27701481
TI  - The effects of the metabolic syndrome on coronary artery bypass grafting surgery.
AB  - BACKGROUND: The metabolic syndrome (MS) is a clustering of factors that are
      associated with increased cardiovascular risk. A low-grade inflammatory process
      acts as the underlying pathophysiology, which suggests that the MS may have a
      detrimental effect on coronary interventions, including coronary artery bypass
      grafting (CABG) surgery performed with cardiopulmonary bypass (CPB). We aimed to
      evaluate the effect of the MS on morbidity and mortality rates in the early
      postoperative period in patients undergoing CABG. METHODS: We prospectively
      included 152 patients (109 males and 43 females; mean age 60.1 +/- 8.6 years) who
      underwent elective CABG on CPB between January and September 2011. Early
      postoperative morbidity and mortality rates were compared between subjects with
      and without the MS. Diagnosis of the MS was based on the American National
      Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria.
      RESULTS: Of the study group, 64 patients (42%) had the MS. The two groups were
      similar in age and gender. In the postoperative period, rates of atrial
      fibrillation, wound infection, pulmonary complications, and lengths of
      intubation, hospitalisation and intensive care unit stay were significantly
      higher in MS patients (p < 0.01). The MS was significantly associated with wound
      infection (OR 6.64, 95% CI: 1.72-25.75), pulmonary complications (OR 6.44, 95%
      CI: 1.58-26.33), arrhythmia (OR 5.47, 95% CI: 1.50-19.97) and prolonged
      intubation (OR 1.17, 95% CI: 1.05-1.32). The mortality rate was 3.1% in the MS
      group and 1.1% in the non-MS group, with no significant difference (p > 0.05).
      CONCLUSION: The MS was associated with a higher rate of early postoperative
      morbidity following CABG, without having a significant effect on the mortality
      rate.

PMID- 27701482
TI  - Presentation and mortality of patients hospitalised with acute heart failure in
      Botswana.
AB  - INTRODUCTION: Heart failure is a common cause of hospitalisation and therefore
      contributes to in-hospital outcomes such as mortality. In this study we describe
      patient characteristics and outcomes of acute heart failure (AHF) in Botswana.
      METHODS: Socio-demographic, clinical and laboratory data were collected from 193
      consecutive patients admitted with AHF at Princess Marina Hospital in Gaborone
      between February 2014 and February 2015. The length of hospital stay and 30-, 90-
      and 180-day in-hospital mortality rates were assessed. RESULTS: The mean age was
      54 +/- 17.1 years, and 53.9% of the patients were male. All patients were
      symptomatic (77.5% in NYHA functional class III or IV) and the majority (64.8%)
      presented with significant left ventricular dysfunction. The most common
      concomitant medical conditions were hypertension (54.9%), human immuno-deficiency
      virus (HIV) (33.9%), anaemia (23.3%) and prior diabetes mellitus (15.5%).
      Moderate to severe renal dysfunction was detected in 60 (31.1%) patients.
      Peripartum cardiomyopathy was one of the important causes of heart failure in
      female patients. The most commonly used treatment included furosemide (86%), beta
      blockers (72.1%), angiotensin converting enzyme inhibitors (67.4%),
      spironolactone (59.9%), digoxin (22.1%), angiotensin receptor blockers (5.8%),
      nitrates (4.7%) and hydralazine (1.7%). The median length of stay was nine days,
      and the in-hospital mortality rate was 10.9%. Thirty-, 90- and 180-day case
      fatality rates were 14.7, 25.8 and 30.8%, respectively. Mortality at 180 days was
      significantly associated with increasing age, lower haemoglobin level, lower
      glomerular filtration rate, hyponatraemia, higher N-terminal pro-brain
      natriuretic peptide levels, and prolonged hospital stay. CONCLUSIONS: AHF is a
      major public health problem in Botswana, with high in-hospital and post-discharge
      mortality rates and prolonged hospital stays. Late and symptomatic presentation
      is common, and the most common aetiologies are preventable and/or treatable co
      morbidities, including hypertension, diabetes mellitus, renal failure and HIV.

PMID- 27701483
TI  - A rare giant pericardial cyst mimicking a paracardiac mass.
AB  - Pericardial cysts are rare benign lesions of the thoracic cavity and are mostly
      congenital anomalies. They are induced by an incomplete coalescence of foetal
      lacunae during the development of the pericardium. Pericardial cysts are usually
      unilocular, well marginated spherical or teardrop shaped and may be attached to
      the pericardium directly or by a pedicle. Of all pericardial cysts, 70 to 75% are
      located at the right cardiophrenic angle. We report a case that was incidentally
      diagnosed with only chest magnetic resonance imaging because of a paracardiac
      mass. In order to prevent complications, the giant pericardial cyst was excised
      outside of the pericardium with median sternotomy.

PMID- 27701485
TI  - Pre-anesthetic echocardiographic findings in children undergoing non-cardiac
      surgery at the University of Benin Teaching Hospital, Nigeria.
AB  - BACKGROUND: A pre-anaesthestic echocardiogram (echo) is requested for most non
      cardiac surgeries to identify possible cardiac structural anomalies. OBJECTIVE:
      To describe the prevalence and spectrum of structural cardiac abnormalities seen
      in various non-cardiac conditions. METHODS: We carried out a retrospective review
      of pre-anaesthetic echos performed over five years on children scheduled for non
      cardiac surgery. The requests were categorised according to referring
      specialities, and the biodata and echo findings were noted. RESULTS: A total of
      181 children and 181 echocardiograms were studied, and 100 (55.2%) of the
      patients were male. Most of the children (87, 48.1%) with oro-facial clefts were
      referred from dentistry. Of the 181 children, 39 (21.5%) had cardiac
      abnormalities, most (34, 87.2%) of whom had congenital heart disease (CHD).
      Ophthalmic requests with suspected congenital rubella syndrome (CRS) had the
      highest prevalence of 8/12 (66.7%) while the lowest was oro-facial clefts at
      15/87 (17.2%). Atrial septal defect was the commonest abnormality, found in 14
      patients (35.9%). CONCLUSION: Pre-anaesthetic echo should be performed,
      especially for children with suspected CRS and other congenital anomalies,
      requiring non-cardiac surgery.

PMID- 27701484
TI  - Comparative analysis of anthropometric indices of obesity as correlates and
      potential predictors of risk for hypertension and prehypertension in a population
      in Nigeria.
AB  - BACKGROUND: Obesity is a well-established independent risk factor for
      hypertension and other cardiometabolic disorders. However, the best
      anthropometric index of obesity that predicts or associates strongly with
      hypertension and related conditions remains controversial and inconclusive.
      OBJECTIVE: This study compared the performance of eight anthropometric indices of
      obesity: body mass index (BMI), ponderal index (PI), waist circumference (WC),
      hip circumference (HC), waist-hip ratio (WHR), waist-height ratio (WHtR), body
      adiposity index (BAI) and conicity index (CI) as correlates and potential
      predictors of risk of hypertension and prehypertension in a Nigerian population,
      and also the possible effect of combining two or more indices in that regard.
      METHODS: This church-based, cross-sectional study was conducted in Anambra state,
      south-eastern Nigeria from 2012 to 2013. A total of 912 persons (436 male and 476
      female) drawn randomly from three major cities (Awka, Onitsha and Nnewi) in the
      state participated in the study. Information on demography, medical history and
      lifestyle were obtained using a well-structured and validated questionnaire. The
      systolic/diastolic blood pressure and anthropometric measurements were taken by
      well-trained personnel. The resulting data were analysed using descriptive
      statistics, logistic regression, Poisson regression and receiver operating
      characteristic curve analysis. RESULTS: The mean values of all the anthropometric
      indices studied increased from normotension, through prehypertension to
      hypertension in both genders. BMI, WC, HC and CI were significantly higher (p <
      0.05) in females than males. All the anthropometric indices studied were
      significantly (p < 0.001 except for CI) correlated with systolic and diastolic
      blood pressure. BMI, WHtR, WC and PI (with higher correlation coefficients for
      blood pressure) showed the best potential to predict hypertension and
      prehypertension in the study: BMI (cut-off = 24.49, AUC = 0.698; cut-off = 23.62,
      AUC = 0.659), WHtR (cut-off = 0.55, AUC = 0.682; cut-off = 0.5, AUC = 0.636), WC
      (cut-off = 91.44, AUC = 0.692; cut-off = 82.55, AUC = 0.645), PI (cut-off =
      14.45, AUC = 0.670; cut-off = 13.69, AUC = 0.639), in males; and BMI (cut-off =
      24.44, AUC = 0.622; cut-off = 28.01, AUC = 0.609), WHtR (cut-off = 0.51, AUC =
      0.624; cut-off = 0.6, AUC = 0.572), WC ( cut-off = 96.62, AUC = 0.616; cut-off =
      96.52, AUC = 0.584), PI ( cut-off = 16.38, AUC = 0.619; cut-off = 17.65, AUC =
      0.599), in females for hypertension and prehypertension, respectively. In
      predicting hypertension risk, WC and WHtR did not significantly improve the
      performance of BMI in the models when included using our decision rule. Overall,
      CI had a very poor discriminatory power for both conditions in this study.
      CONCLUSION: BMI, WHtR, WC and PI emerged the best predictors of hypertension
      risk, and BMI, WC and PI of prehypertension risk in this study. The combination
      of high-performing anthropometric indices in a model did not improve their
      performance. Therefore we recommend the simultaneous but independent use of BMI
      and either WC or WHtR for predicting hypertension, and BMI and WC for
      prehypertension risk, bearing in mind that both types of index (abdominal and
      general obesity) account for different forms of obesity.

PMID- 27701486
TI  - Relationship between Vitamin D and the development of atrial fibrillation after
      on-pump coronary artery bypass graft surgery.
AB  - BACKGROUND: Vitamin D deficiency is associated with many diverse cardiovascular
      disorders, such as hypertension, heart failure, stroke, coronary artery disease
      and atrial fibrillation. The relationship between Vitamin D and the development
      of atrial fibrillation after coronary artery bypass surgery (CABG) has not been
      studied. Therefore, we assessed the relationship between Vitamin D and the
      development of postoperative atrial fibrillation (POAF) after CABG. METHODS:
      Medical records of consecutive patients who underwent CABG surgery were
      retrospectively reviewed for the development of atrial fibrillation in the
      postoperative period. Vitamin D, other biochemical parameters, and clinical and
      echocardiographic parameters were evaluated in all patients. The independent
      variables for the development of postoperative atrial fibrillation were defined
      and their predictive values were measured. RESULTS: The study group consisted of
      128 patients, of whom 41 (32%) developed POAF. Age, diabetes mellitus, chronic
      obstructive pulmonary disease, history of transient ischaemic attack/stroke,
      heart failure, left atrial diameter, platelet:largecell ratio, and creatinine,
      urea, uric acid, calcium and potassium levels were identified as important
      variables for the development of POAF. However, with logistic regression
      analysis, chronic obstructive pulmonary disease (OR: 28.737, 95% CI: 0.836
      16.118, p < 0.001), heart failure (OR: 15.430, 95% CI: 0.989-7.649, p = 0.006),
      diabetes mellitus (OR: 11.486, 95% CI: 0.734-11.060, p = 0.001) and left atrial
      diameter (OR: 1.245, 95% CI: 0.086-6.431, p = 0.011) appeared as independent
      variables predicting the development of POAF. CONCLUSION: In our study, although
      there was a significant negative correlation between Vitamin D and left atrial
      diameter, Vitamin D level was not an independent predictor for POAF.

PMID- 27701487
TI  - The effect of proximal anastomosis on the expansion rate of a dilated ascending
      aorta in coronary artery bypass surgery: a prospective study.
AB  - BACKGROUND: This study was designed to determine the short- and long-term effects
      of proximal aortic anastomosis, performed during isolated coronary artery bypass
      grafting (CABG) in patients with dilatation of the ascending aorta who did not
      require surgical intervention. METHODS: The study was performed on 192 (38 female
      and 160 male patients; mean age, 62.1 +/- 9.2 years; range, 42-80 years) patients
      with dilatation of the ascending aorta who underwent CABG surgery between 1 June
      2006 and 31 May 2014. In group 1 (n = 114), the saphenous vein and left internal
      mammarian artery grafts were used, and proximal anastomosis was performed on the
      ascending aorta. In group 2 (n = 78), left and right internal mammarian artery
      grafts were used, and proximal aortic anastomosis was not performed. Pre
      operatively and in the first and third years postoperatively, the ascending
      aortic diameter was measured and recorded using transthoracic echocardiography at
      four different regions (annulus, sinus of Valsalva, sinotubular junction and
      tubular aorta). RESULTS: A statistically significant difference was found between
      the groups for the number of grafts used and the duration of aortic cross
      clamping and cardiopulmonary bypass. No significant intergroup difference was
      seen for the mean diameter of the ascending aorta (p > 0.05). Annual changes in
      the aortic diameter were found to be extremely significantly different in both
      groups (p = 0.0001). Mean values of the aortic diameter at the level of the
      sinotubular junction and tubular ascending aorta, mean aortic diameters (p =
      0.002 and p = 0.0001, respectively), annual increase in diameter (p = 0.0001 and
      p = 0.0001, respectively), and mean annual difference in diameter (p = 0.0001 and
      p = 0.0001, respectively) at one and three years postoperatively were
      statistically significantly different between the groups. CONCLUSION: In patients
      with ascending aortic dilatation who did not require surgical intervention and
      who had proximal anastomosis of the ascending aorta and underwent only CABG, we
      detected statistically significant increases in the diameter of the sinotubular
      junction and tubular aorta up to three years postoperatively.

PMID- 27701488
TI  - Xanthine oxidase inhibitors in ischaemic heart disease.
AB  - Increased uric acid levels are correlated with cardiovascular disease,
      particularly with ischaemic heart disease. Xanthine oxidase inhibitors,
      especially allopurinol, lower the risk of ischaemic heart disease due to their
      effects on reactive oxygen species and endothelial function. In chronic stable
      angina pectoris, allopurinol increases the median time to ST depression, time to
      chest pain, and total exercise time. On the other hand, it has been reported that
      allopurinol has a beneficial effect on ischaemic patients referred for
      angioplasty, but there are insufficient data regarding its effect on acute
      myocardial infarction patients. Moreover, other important actions of allopurinol
      are regression of left ventricular hypertrophy and improvement in the results of
      cardiac rehabilitation. The efficacy of allopurinol has recently been
      acknowledged by the European Society of Cardiology guidelines for stable angina
      pectoris, but the particular role of allopurinol in ischaemic heart disease
      patients is not fully established.

PMID- 27701489
TI  - Prevalence of selected cardiometabolic risk factors among adults in urban and
      semi-urban hospitals in four sub-Saharan African countries.
AB  - AIM: Cardiovascular diseases (CVDs) are a global challenge but the burden in sub
      Saharan African (SSA) countries is less well documented than elsewhere. We aimed
      to describe the key cardiometabolic risk factors in four SSA countries. METHODS:
      A cross-sectional, multi-national, hospital-based study was carried out among
      adults (> 35 years) across four SSA countries from 12 December 2011 to 7 February
      2013. Risk factors were defined using the World Health Organisation and
      International Diabetes Federation guidelines. RESULTS: Of the 844 adults (57.4%
      female, mean age 52.6 years), 76.6% were urban residents. The predominant CVD
      risk factors were hypertension (74.1%), obesity (36.2%) and excessive alcohol
      consumption (25.6%). Diabetes (17.7 vs 10.0%), obesity (42.8 vs 16.8%) and
      hypercholesterolaemia (25.8 vs 18.0%) were more prevalent among the hypertensive
      subjects (all p < 0.007) than the normotensives. The metabolic syndrome (39.4%)
      was more common in women and hypertensive subjects. CONCLUSIONS: Hospital
      patients in SSA countries present with excessive rates of cardiometabolic risk
      factors. Focus on their prevention and control is warranted.

PMID- 27701491
TI  - In memoriam. Prof. Dr. Maria Beatriz Guglielmotti.

PMID- 27701490
TI  - Audit of availability and distribution of paediatric cardiology services and
      facilities in Nigeria.
AB  - BACKGROUND: Paediatric cardiac services in Nigeria have been perceived to be
      inadequate but no formal documentation of availability and distribution of
      facilities and services has been done. OBJECTIVE: To evaluate and document the
      currently available paediatric cardiac services in Nigeria. METHODS: In this
      questionnaire-based, cross-sectional descriptive study, an audit was undertaken
      from January 2010 to December 2014, of the personnel and infrastructure, with
      their distributions according to geopolitical zones of Nigeria. RESULTS: Forty
      eight centres participated in the study, with 33 paediatric cardiologists and 31
      cardiac surgeons. Echocardiography, electrocardiography and pulse oximetry were
      available in 45 (93.8%) centres while paediatric intensive care units were in 23
      (47.9%). Open-heart surgery was performed in six (12.5%) centres. South-West zone
      had the majority of centres (20; 41.7%). CONCLUSIONS: Available paediatric
      cardiac services in Nigeria are grossly inadequate and poorly distributed.
      Efforts should be intensified to upgrade existing facilities, establish new and
      functional centres, and train personnel.

PMID- 27701492
TI  - Repairability of aged resin composites mediated by different restorative systems.
AB  - The aim of this study was to evaluate the shear bond strength of resin composite
      repairs with and without aging of the surface to be repaired, using different
      adhesive systems and resin composites. Ninety specimens were prepared: 10 for the
      Control Group (GC - without repair); 40 for Group I (GI - repairs after 7 days)
      and 40 for Group II (GII - repairs after 180 days). Groups I and II were divided
      into 4 subgroups of 10 specimens each, according to the adhesive system and
      composite resin used: A) Adper Scotch Bond Multipurpose + Filtek Z350 XT; B)
      Adper Single Bond Plus + Filtek Z350 XT; C) Adper Scotch Bond Multipurpose +
      Esthet-X; D) Adper Single Bond Plus + Esthet-X. The specimens were tested for
      shear strength in a universal testing machine. The results were analyzed by two
      factor one-way ANOVA and Fisher's post hoc tests (alpha=0.05). The control group
      had better performance than the other groups. There was no significant difference
      when comparing different adhesive systems and composite resins. Repairs performed
      at 7 days were better than those performed at 180 days. The composite repairs
      decreased the mechanical strength of the restoration. Aging of the resin
      substrate may decrease repair bond strength over time, regardless of the type of
      adhesive systems and resin composites used.

PMID- 27701493
TI  - Study and analysis of information technology in dentistry in Latin American
      countries.
AB  - : Dentistry increasingly uses Information and Communication Technology (ICT),
      which has impact on teaching, research, the profession and dental care in
      general. However, there is a lack of valid information on ICT resources and use
      in Latin America. This was a descriptive, cross-sectional, multi-center,
      interdisciplinary study, the aim of which was to conduct a survey on how
      extensively ICT is used in Dentistry in Latin American countries by enquiring
      into two primary components: 1) use of ICT in student training and 2) use of ICT
      by professionals in consulting rooms and services. Two questionnaires on ICT were
      prepared: one for teachers/researchers and another for students/professionals. We
      received 94 answers from teachers/researchers at universities in the region
      providing information on ICT resources for teaching (type and implementation) and
      221 answers from professionals (personal use and use in healthcare). Data are
      presented as absolute relative frequencies and analyzed quantitatively as
      percentages. RESULTS: 1) Teachers highlight ICT as an instrument for development,
      democratization and fairness in access to knowledge for higher education. 2) ICT
      supports collaborative learning and generates other innovative resources (e.g.
      simulators). 3) Innovations in telemedicine and experiences with electronic
      clinical history were identified in Brazil, Uruguay and Colombia. These results
      are a basis upon which to reach a consensus regarding a set of ICT indicators
      which are comparable at regional level and serve as input to unify the design and
      implementation of ICTs experiences in both teaching and dental care in Latin
      America.

PMID- 27701494
TI  - Craniofacial pain can be the sole prodromal symptom of an acute myocardial
      infarction: an interdisciplinary study.
AB  - We recently found craniofacial pain to be the sole symptom of an acute myocardial
      infarction (AMI) in 4% of patients. We hypothesized that this scenario is also
      true for symptoms of prodromal (pre-infarction) angina. We studied 326
      consecutive patients who experienced myocardial ischemia. Intra-individual
      variability analyses with respect to ECG findings and pain characteristics were
      performed for those 150 patients who experienced at least one recurrent ischemic
      episode. AMI patients (n=113) were categorized into two subgroups: "abrupt onset"
      (n=81) and "prodromal angina" (n=32). Age, gender and risk factor comparisons
      were performed between groups. Craniofacial pain constituted the sole prodromal
      symptom of an AMI in 5% of patients. In those who experienced two ischemic
      episodes, women were more likely than men to experience craniofacial pain in both
      episodes (p<0.01). There was no statistically significant difference between
      episodes regarding either ECG findings or the use of the two typical pain quality
      descriptors "pressure" and "burning". This study is to our knowledge the first to
      report that craniofacial pain can be the only symptom of a pre-infarction angina.
      Craniofacial pain constitutes the sole prodromal AMI symptom in one out of 20 AMI
      patients. Recognition of this atypical symptom presentation is low because
      research on prodromal AMI symptoms has to date studied only patients with chest
      pain. To avoid a potentially fatal misdiagnosis, awareness of this clinical
      presentation needs to be brought to the attention of clinicians, researchers and
      the general public.

PMID- 27701496
TI  - Post-bleaching sensitivity in patients with sickle cell disease.
AB  - Sickle cell disease (SCD) is a monogenic disease that affects millions of people
      worldwide. This study analyzed the effectiveness of bleaching and tooth
      sensitivity after in-office bleaching in patients with SCD. Forty volunteers were
      randomly assigned to four groups of 10 patients each (five with the SCD and five
      healthy controls) and treated using in-office bleaching with 35% hydrogen
      peroxide and different light activation protocols. No statistically significant
      difference was observed with relation to presence of tooth sensitivity, with or
      without use of a source of light for peroxide activation, and all bleaching
      therapies were effective, regardless of the technique employed and the
      presence/absence of sickle cell disease. The data showed that in-office dental
      bleaching is a viable alternative for improvement of oral esthetics for patients
      with SCD.

PMID- 27701495
TI  - Association between periodontal disease and endothelial dysfunction in smoking
      patients.
AB  - Over the past two decades, there has been increasing interest in the impact of
      oral health on cardiovascular disease, particularly regarding the effects of
      chronic infections such as periodontitis on the endothelium. The aim of this
      study was to evaluate in healthy smokers whether there are any significant
      differences in the frequency of endothelial dysfunction between subjects with
      chronic moderate to severe periodontal disease and periodontally healthy
      subjects. An observational cross-sectional study was conducted. The target
      population was adults older than 40 years of age. Blood tests were performed to
      determine values of CBC, glycaemia, total cholesterol, HDL-C, and LDLC.
      Periodontal examinations and probing were conducted with a Florida Probe(r), and
      standardized procedures were used to measure flow-mediated dilation. Out of 150
      subjects [69 male (46%) and 81 female (54%)], 75 (50%) had chronic periodontitis.
      The mean value for baseline flow-mediated dilation was 4.04% and the mean value
      for final flow-mediated dilation was 4.66%, with a 0.62% mean difference showing
      a statistically significant increase (p<0.001).This study found no significant
      difference in the flow-mediated dilation values between periodontally healthy
      subjects and those with periodontitis, in contrast to the literature, which
      suggests a negative impact of periodontal disease on endothelial function.

PMID- 27701497
TI  - Nickel allergy: blood and periodontal evaluation after orthodontic treatment.
AB  - The aim of this study was to assess periodontal status and blood parameters in
      orthodontic patients with nickel allergy one month after removal of brackets.
      Ninety-six randomly selected patients were initially evaluated. Allergy to nickel
      was diagnosed using a patch test. After determining the prevalence of subjects
      allergic to nickel, two groups were formed: 16 allergic (experimental) and 16 non
      allergic (control) patients. Their periodontal status was determined regularly by
      a single, blinded, duly calibrated examiner using the Loe Index (GI) and their
      blood was tested (complete blood test, including nickel and IgE levels) after
      nine months of orthodontic treatment and again one month after removing the
      orthodontic appliances. Statistical analyses included paired and non-paired t
      tests, Mann-Whitney, Wilcoxon, McNemar and linear trend chi-square tests
      (p<=0.05). Comparison of the values recorded during orthodontic treatment and one
      month after removing the appliances showed that in the allergic group there was
      significant increase in eosinophils (p=0.046), basophils (p=0.001) and monocytes
      (p=0.002), and decrease in number of bands (p=0.000), while in the control group,
      there was increase in lymphocytes (p=0.039) and decrease in segmented neutrophils
      (p=0.030) and IgE levels (p=0.001). In both groups, plasma nickel levels
      increased (p=0.010; p=0.039) and GI scores decreased. One month after removing
      the brackets, blood and periodontal parameters from patients with and without
      nickel allergy were similar.

PMID- 27701498
TI  - Creatine metabolism: detection of creatine and guanidinoacetate in saliva of
      healthy subjects.
AB  - Creatine (Cr) plays an important role in storage and transmission of phosphate
      bound energy. Cerebral creatine deficiency syndromes comprise three inherited
      defects in Cr biosynthesis and transport. The aim of this study was to
      investigate whether Cr and Guanidinoacetate (GAA) can be detected in saliva of
      healthy subjects and to establish the relationship between salivary and plasma
      levels of these molecules. An adapted gas chromatography (GC) method is described
      for the quantification of Cr and GAA biomarkers in saliva. Reference values were
      established for GAA and Cr in saliva. These values were age dependent (p= 0.001).
      No difference between genders was observed. We detected a difference between GAA
      and Cr concentrations in saliva and in plasma. The GC method for simultaneous
      determination of GAA and Cr in human saliva is fast, reliable, sensitive, non
      invasive and precise to use as a biochemical approach in early detection of
      cerebral creatine deficiency syndromes.

PMID- 27701499
TI  - Frequency of the mesiopalatal canal in upper first permanent molars viewed
      through computed tomography.
AB  - The success of any endodontic therapy depends on factors such as correct
      diagnosis and prognosis. Unawareness or failure to locate additional canals, such
      as the mesiopalatal canal in the upper first molar, may lead to unsuccessful
      treatment. Hence, it is valid to consider all the resources available for
      locating this anatomic structure, e.g. the Cone-Beam Computed Tomography (CBCT).
      The purpose of this study was to verify the frequency of mesiopalatal canals in
      upper first permanent molars through computed tomography. Tomography images from
      a digital archive of a diagnostic imaging center were analyzed. Eighty (80) upper
      right first molars were assessed through CBCT in axial cross sections at 6mm and
      3mm from the root apex; 40 were females and 40, males, randomly chosen. The
      results revealed that the mesiopalatal canals were present in 56.25% of the
      sections at 6mm from the root apex, and in 23.75% at 3mm from the apical limit.
      CBCT scan has proved to be a valid resource for locating mesiopalatal canal,
      especially in cases where location was not feasible through clinical means.

PMID- 27701500
TI  - Effect of angiotensin-converting enzyme inhibitors on vascular endothelial
      function in hypertensive patients after intensive periodontal treatment.
AB  - : There is a relation between vascular endothelial function, atherosclerotic
      disease, and inflammation. Deterioration of endothelial function has been
      observed twenty-four hours after intensive periodontal treatment. This effect may
      be counteracted by the action of angiotensin-converting enzyme inhibitors, which
      improve endothelial function. The aim of the present study was to evaluate
      vascular endothelial function after intensive periodontal treatment, in
      hypertensive patients treated with angiotensinconverting enzyme inhibitors. A
      prospective, longitudinal, comparative study involving repeated measurements was
      conducted. Fifty-two consecutive patients with severe periodontal disease were
      divided into two groups, one comprising hypertensive patients treated with
      converting enzyme inhibitors and the other comprising patients with no clinical
      signs of pathology and not receiving angiotensin-converting enzyme inhibitors.
      Endothelial function was assessed by measuring postischemic dilation of the
      humeral artery (baseline echocardiography Doppler), and intensive periodontal
      treatment was performed 24h later. Endothelial function was re-assessed 24h and
      15 days after periodontal treatment. STATISTICAL ANALYSIS: Results were analyzed
      using the SPSS 20 statistical software package. Student's t test and MANOVA were
      calculated and linear regression analysis with 95% confidence intervals and
      alpha<0.05 was performed. Arterial dilation at 24 hours was lower compared to
      baseline in both groups; values corresponding to the groups receiving angiotensin
      converting enzyme inhibitors were 11.89 +/- 4.87 vs. 7.30 +/- 2.90% (p<0.01) and
      those corresponding to the group not receiving ACE inhibitors were 12.72 +/- 4.62
      vs. 3.56 +/- 2.39 (p<0.001). The differences between groups were statistically
      significant (p<0.001). CONCLUSION: The increase in endothelial dysfunction after
      intensive periodontal treatment was significantly lower in hypertensive patients
      treated with angiotensin-converting enzyme inhibitors. Endothelial function
      improved 15 days after periodontal treatment, reaching baseline values. These
      results support the protective effect of angiotensin converting enzyme inhibitors
      on the endothelial function after intensive periodontal treatment.

PMID- 27701501
TI  - Dental bleaching with ozone: effects on color and enamel microhardness.
AB  - The aim of this in vitro study was to evaluate the effects of dental bleaching
      with ozone (O3) on color change and enamel microhardness. Enamel blocks (3 x 3 x
      3mm) were randomly distributed for treatments (n=10). Color change (DeltaE) and
      Knoop microhardness of the enamel blocks were evaluated before and after the
      following treatments: C - deionized water (control); HP - 37.5% hydrogen peroxide
      (Pola Office+/ SDI); PLA - placebo gel; O3 - ozone; and O2 - oxygen. Four 8
      minute applications were used for HP and PLA, and one 19-minute application for
      O3 and O2.One-way ANOVA revealed that DeltaE was not significantly influenced by
      the treatment (p = 0.112). For the treatments with HP, PLA, O3 andO2, DeltaE was
      greater than 3.3. The paired t test showed significant decrease in microhardness
      after treatments (p < 0.001) but no significant difference between treatments
      (ANOVA; p = 0.313). Dental bleaching treatments with O3, HP, O2 and PLA induced
      enamel color changes that may be clinically discernible, although enamel
      microhardeness decreased.

PMID- 27701502
TI  - Efficacy of three thermoplastic obturation techniques in filling oval-shaped root
      canals.
AB  - The purpose of this study was to assess the efficacy of the thermoplastic filling
      techniques, Touch'n Heat(r), TC(r) System and Tagger's Hybrid Technique, in oval
      shaped canals at the apical third.Thirty-three human uniradicular lower pre-molar
      teeth were treated by the reciprocating movement technique and were subsequently
      split into 3 groups, according to the filling technique performed:Touch'n Heat
      (TH), TC System (TC) and the Tagger's Hybrid Technique (TG).In the sequence, the
      teeth were sectioned at 2mm and 4mm from the foramen and images were taken to
      measure the percentage of canal area filled with the obturation materials as well
      as void spaces.Data were submitted for Kruskal-Wallis statistical analysis.
      Irrespective of levels, data showed that the TC System delivered the best
      results.(p<0,001).At 2mm and 4mm levels, there was no difference between the TG
      technique and the TH technique (p<0,001).With all the techniques and at all
      levels, no differences were observed regarding the void area
      variable.(p>0,001).The techniques evaluated showed an adequate filling with
      obturation materials and the TC has reached the highest filling with the guta
      percha material.

PMID- 27701503
TI  - Toothbrushing procedure in schoolchildren with no previous formal instruction:
      variables associated to dental biofilm removal.
AB  - The aim of this study was to establish the association between features regarding
      brushing procedure performed by schoolchildren without previous formal training
      and the effectiveness of biofilm removal. Out of a population of 8900 6- and 7
      year-old schoolchildren in Buenos Aires City, 600 children were selected from
      schools located in homogeneous risk areas. Informed consent was requested from
      parents or guardians and formal assent was obtained from children themselves. The
      final sample consisted of 316 subjects. The following tooth brushing variables
      were analyzed: toothbrush-gripping, orientation of active part of bristles with
      respect to the tooth, type of movement applied, brushing both jaws together or
      separately, including all 6 sextants and duration of brushing. The level of
      dental biofilm after brushing was determined by O'Leary's index, acceptable cut
      off point = 20%. Four calibrated dentists performed observations and clinical
      examinations. Frequency distribution, central tendency and dispersion measures
      were calculated. Cluster analyses were performed; proportions of variables for
      each cluster were compared with Bonferroni's correction and OR was obtained. The
      most frequent categories were: palm gripping (71.51%); perpendicular orientation
      (85.8%); horizontal movement (95.6%); separate addressing of jaws (68%) and
      inclusion of all 6 sextants (50.6%). Mean duration of brushing was 48.78 +/-
      27.36 seconds. 42.7% of the children achieved an acceptable biofilm level. The
      cluster with the highest proportion of subjects with acceptable post-brushing
      biofilm levels (p<0.05) differed significantly from the rest for the variable
      "inclusion of all 6 sextants in brushing procedure". OR was 2.538 (CI 95% 1.603 -
      4.017). Inclusion of all six sextants could be a determinant variable for the
      removal of biofilm by brushing in schoolchildren, and should be systematized as a
      component in oral hygiene education.

PMID- 27701504
TI  - Neurogenetic disorders in Saudi Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701505
TI  - Acute flaccid paralysis by non-polio exteroviruses before, during and after
      eradication of poliomyelitis.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701506
TI  - Did the national campaign for poliomyelitis vaccination achieve its objectives.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701507
TI  - Factors affecting cerebrospinal fluid shunt revision rate in children at King
      Khalid University Hospital.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701508
TI  - Finasteride for hirsutism: a dose finding study.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701509
TI  - Piracetam for the treatment of sickle cell disease in children- a double blind
      test.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701510
TI  - Assessment of physician's prescribing practices at Ministry of Health Hospitals
      in Jeddah City - Saudi Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701511
TI  - Fluoride content of bottle drinking water in Saudi Arabia and its relation to the
      prescription of preventive regimens.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701512
TI  - A critical analysis of orthopedic work load in a teaching hospital in the United
      Arab Emirates as a stimulus for improving patient care.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701513
TI  - Treatment of proximal third femoral shaft fractures in children by intramedullary
      Kirschner wires.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701515
TI  - Should diabetic pregnant mothers fast during Ramadan?
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701514
TI  - Diabetic foot: presentation and surgical management at Dammam Central Hospital.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701516
TI  - The safety of pediatric blunt abdominal trauma in the hands of general surgeons.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701517
TI  - Inflammatory bowel disease in Saudi Arabia - non-operative and operative
      management at King Faisal Specialist Hospital.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701519
TI  - Promotion of physical exercise by primary health care physicians in Riyadh city.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701518
TI  - The effect of delayed fixation on the demonstration of AgNORs adenocarcinoma.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701520
TI  - Learning objectives of medical students: What is the message.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701521
TI  - Localized pigmented villonodular synovitis in the knee of a young girl diagnosed
      by Ultrasound.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701522
TI  - Intrathoracic kidney - a rare incidental finding.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701523
TI  - Vesical calculus on a foreign body- a case report.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701524
TI  - Mumps virus encephalitis can mimic herpes simplex encephalitis.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701525
TI  - The importance of the computer in medical education.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701526
TI  - Seismophobia: there is no loss worse than the loss of faith in the ground under
      us!
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701527
TI  - Challenges encountered in commissioning of new health care facilities: Radiology
      Department experience.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701528
TI  - Verse.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701529
TI  - Skin response to pressure and ageing.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701530
TI  - Prescription for health cost control.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701531
TI  - Physicians and health organization management.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701533
TI  - Therapeutic options for psoriasis: Review and update.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701532
TI  - Undergraduate Curriculum Reform in Saudi Medical Schools, needed or not?
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701535
TI  - Normal developmental milestones: Comparison of Urban and Rural children in
      Madinah, Saudi Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701534
TI  - Hereditary anemias in Lebanon.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701536
TI  - Evaluation of antenatal services in a primary health care setting in Riyadh.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701537
TI  - The relation between pre-eclampsia and chemical constituents of drinking waters
      in Saudi Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701538
TI  - Blood groups in Saudi obstetrics patients.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701539
TI  - Frequency of various Rh antigens in Dammam Eastern Province, Saudi Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701541
TI  - Bone marrow examination in staging of Lymphoma: Revisited.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701540
TI  - Plasma fibrinogen and cardiovascular disease in Syria.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701542
TI  - Why immunization appointment fails? Study in a Primary Health Care Center.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701543
TI  - Seroepidemiological prevalence of hepatitis B virus markers in Eastern Saudi
      Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701544
TI  - Toxoplasma antibody prevalence among healthy adults in United Arab Emirates.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701545
TI  - Group A B Hemolytic Streptococci in rheumatic patients receiving long acting
      penicillin.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701546
TI  - Brucellosis in a rural community.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701547
TI  - Management of foot lesions in 310 diabetics.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701548
TI  - Clinical prediction rule for pulmonary infiltrates.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701550
TI  - Ramadan fasting and renal failure.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701549
TI  - Metabolic consequences of date snack before a meal: A traditional Arab practice.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701551
TI  - Prevalence of primary sclerosing cholangitis in Saudi patients with liver
      disease.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701552
TI  - Sonographic imaging of appendix testis and appendix epididymis.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701554
TI  - Dental anomalies in children with cleft lip and/or palate or both.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701553
TI  - Functional treatment of acute ankle sprain.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701555
TI  - Discriminating variables between insured and uninsured patients.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701556
TI  - Pregnancy - associated osteoporosis fact or fantasy?
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701557
TI  - Clostridial species and group D streptococcal septicemia in a pregnant woman:
      Case report and Literature review.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701559
TI  - A unique spectrum of deep vein thrombosis and pulmonary embolism; management
      guidelines.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701558
TI  - Pleurisy in ovarian hyperstimulation syndrome: A case report.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701560
TI  - Aplasia of the columella and cartilaginous nasal septum associated with choanal
      atresia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701561
TI  - Syndrome X.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701562
TI  - Prevention of herniation at the site of cannula insertion after laparoscopic
      cholecystectomy.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701563
TI  - The prescription for health cost control.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701564
TI  - Cholelithiasis in Saudi Females.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701565
TI  - Challenges encountered in commissioning of new health care facilities: Radiology
      Department Experience.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701566
TI  - The heart in rheumatic disease.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701567
TI  - Stress, sympathetic activity and heart disease: Is there any common mediator?
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701568
TI  - Management of emergency department during Haj period.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701569
TI  - Prevalence of hypertension in adult Saudi population.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701570
TI  - Hypercholesterolemia and susceptibility to cardiovascular diseases among white
      and blue collars in Jeddah.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701571
TI  - Prenatal diagnosis, its potential impact on the prevalence and management of
      congenital anomalies.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701572
TI  - A study of infant deaths in a Regional Hospital in Saudi Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701573
TI  - Neonatal perforations of the gastrointestinal tract.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701574
TI  - Juvenile colorectal polyps in children.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701575
TI  - PCR-based analysis of cystic fibrosis mutations specific for Saudi patients.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701576
TI  - The diagnostic approach to suspected asthma in a Primary Care Center in Riyadh.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701578
TI  - Food allergy and chronic urticaria: the value and limits of in vitro testing for
      IgE antibodies specific for food allergens.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701577
TI  - Referral rates and patterns in primary care department, Khamis Mushayt, Saudi
      Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701579
TI  - Carpal Tunnel Sydrome: A prospective clinical study of one hundred cases.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701580
TI  - Survival and prognostic factors in renal cell carcinoma in Saudi patients: A ten
      year review.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701581
TI  - Malignant tumors of upper urinary tract - an experience in Benghazi.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701582
TI  - Babesia parasites described from patients bled for malaria.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701583
TI  - Hepatitis C virus detection and genotyping in liver tissues and sera of Saudi
      patients using PCR and a line probe assay.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701585
TI  - Seroprevalence of syphilis and HIV in intravenous drug users.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701584
TI  - Education of female students in reproductive health issues in Jeddah: the role of
      school workers.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701586
TI  - Management of unusual tumors of the pediatric cerebellum: report of three cases
      and review of the literature.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701587
TI  - Reversible acute renal failure due to oral acyclovar.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701588
TI  - Unusual local cutaneous reactions to insulin injections: a case report.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701589
TI  - Discontinous splenogonadal fusion mimicking testicular tumor.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701590
TI  - Paget's disease of the bone. A decade since the first reported case.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701591
TI  - Application of some of Iranian medicinal plants in the treatment of liver injury.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701592
TI  - School screening for scoliosis: Have we done enough?
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701594
TI  - Review of non-tuberculous mycobacteria. King Khalid National Guard Hospital,
      Jeddah.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701593
TI  - Closed reduction of colles' fracture: a simple "shake-hands" method.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701595
TI  - Eradication of Helicobacter pylori infection and methonidazole resistance:
      different results in different countries.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701596
TI  - Profile of breast pathology at Asir Central hospital - Review of 312 breast
      cases.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701597
TI  - Falciparum malaria and acute renal failure.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701599
TI  - Signal and Image Processing.

PMID- 27701598
TI  - Salmonella typhi.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27701600
TI  - Digital Libraries.

PMID- 27701601
TI  - The state of clinical information systems after four decades of effort.

PMID- 27701602
TI  - Knowledge Processing and Decision Support Systems.

PMID- 27701603
TI  - University of Utah Medical Informatics Research and Training Program.

PMID- 27701604
TI  - What is bioinformatics? An introduction and overview.

PMID- 27701605
TI  - Research and Education at the Centre for Research and Evaluation in Diagnostics
      (CRED), University of Sherbrooke.

PMID- 27701606
TI  - Information Systems to facilitate Health and Clinical Management.

PMID- 27701607
TI  - Medical informatics in Amsterdam: Research and Education.

PMID- 27701608
TI  - Medical Informatics Research and Education at the Erasmus University in
      Rotterdam.

PMID- 27701609
TI  - From Hospital Information Systems to Health Information Systems - Problems,
      Challenges, Perspectives.

PMID- 27701610
TI  - Toward a medical information collective: trends in the development of digital
      libraries in medicine.

PMID- 27701611
TI  - Education.

PMID- 27701612
TI  - Computer-based Patient Records.

PMID- 27701613
TI  - Seeking the digital library.

PMID- 27701614
TI  - Digital Libraries and Medicine.

PMID- 27701615
TI  - [Evaluation of a new device for sample collection, transport and detection of
      Group B Streptococcus in pregnant women].
AB  - We have designed a new device that combines sample collection, transportation,
      culture and detection of Group B Streptococcus (GBS), requiring no additional
      processing in the clinical laboratory. The objective was to evaluate the
      performance of this device for GBS detection in pregnant women. The new prototype
      was compared to direct plating of vaginal-rectal swabs onto Granada solid media
      plates. Direct plating method detected 124 positive samples out of 600 (20.6%)
      whereas the new device detected 10 additional positive samples (134/600, 22.3%).
      This new device (patent-protected) could be considered for routine GBS screening.

PMID- 27701616
TI  - Pneumonia: burden of disease.

PMID- 27701617
TI  - [Varicella Zoster with fulminant multiorgan failure after high-dose
      corticosteroids].

PMID- 27701618
TI  - [Mycobacterium africanum and Mycobacterium avium co-infection in an AIDS
      patient].

PMID- 27701619
TI  - [Multilocus Sequence Typing analysis of human Campylobacter coli in Granada
      (Spain)].
AB  - OBJECTIVE: Different subtypes of Campylobacter spp. have been associated with
      diarrhoea and a Multilocus Sequence Typing (MLST) method has been performed for
      subtyping. In the present work, MLST was used to analyse the genetic diversity of
      eight strains of Campylobacter coli. METHODS: Nineteen genetic markers were
      amplified for MLST analysis: AnsB, DmsA, ggt, Cj1585c, CJJ81176-1367/1371, Tlp7,
      cj1321-cj1326, fucP, cj0178, cj0755/cfrA, ceuE, pldA, cstII, cstIII. After
      comparing the obtained sequences with the Campylobacter MLST database, the allele
      numbers, sequence types (STs) and clonal complexes (CCs) were assigned. RESULTS:
      The 8 C. coli isolates yielded 4 different STs belonging to 2 CCs. Seven isolates
      belong to ST-828 clonal complex and only one isolate belong to ST-21. Two samples
      came from the same patient, but were isolated in two different periods of time.
      CONCLUSIONS: MLST can be useful for taxonomic characterization of C. coli
      isolates.

PMID- 27701620
TI  - [Interlaboratory controls: more than just a knowledge test].

PMID- 27701621
TI  - Intubation During Pediatric CPR: Early, Late, or Not at All?

PMID- 27701622
TI  - Regeneration of Corneal Epithelium With Dental Pulp Stem Cells Using a Contact
      Lens Delivery System.
AB  - Purpose: The corneal epithelium is sloughed off surface of the eye by the action
      of blinking and is continually replaced by division and maturation of the limbal
      stem cells (LSCs). In the case of injury or disease, LSCs can be lost or damaged
      to a point at which the corneal epithelial layer is no longer maintained. leading
      to LSC deficiencies (LSCDs). When this occurs, the opaque conjunctiva overgrows
      the anterior surface of the eye, leading to vision impairment or loss. Dental
      pulp stem cells (DPSCs) are promising candidates as autologous LSC substitutes.
      In this study, contact lenses (CLs) are used as a novel medical device to deliver
      DPSCs onto corneal surface to enhance corneal epithelium regeneration. Methods:
      Dental pulp stem cells labeled with green fluorescent Qtracker 525 were seeded
      onto the pretreated CLs, allowed to adhere, then delivered to debrided human
      corneas. Expression of KRT3, 12, 13, and 19 was investigated by immunostaining,
      then standard and confocal microscopy. Results: Dental pulp stem cells were
      successfully isolated, labeled, and delivered to the corneal surface using CLs.
      Following removal of CLs, confocal microscopy showed that the DPSCs had migrated
      onto the cornea. Coexpression of KRT12 and green fluorescent Qtracker 525
      confirmed that the DPSCs had transdifferentiated into corneal epithelial
      progenitors. Delimitation of KRT 19 and green fluorescence provides evidence that
      Qtracker 525-labeled DPSCs establish a barrier to the invasion of the cornea by
      conjunctiva. Conclusions: In this study we show that DPSCs, delivered using CLs,
      can be used to enhance repair and regeneration of the human corneal epithelium.

PMID- 27701623
TI  - Association Between Tracheal Intubation During Pediatric In-Hospital Cardiac
      Arrest and Survival.
AB  - Importance: Tracheal intubation is common during pediatric in-hospital cardiac
      arrest, although the relationship between intubation during cardiac arrest and
      outcomes is unknown. Objective: To determine if intubation during pediatric in
      hospital cardiac arrest is associated with improved outcomes. Design, Setting,
      and Participants: Observational study of data from United States hospitals in the
      Get With The Guidelines-Resuscitation registry. Pediatric patients (<18 years)
      with index in-hospital cardiac arrest between January 2000 and December 2014 were
      included. Patients who were receiving assisted ventilation, had an invasive
      airway in place, or both at the time chest compressions were initiated were
      excluded. Exposures: Tracheal intubation during cardiac arrest . Main Outcomes
      and Measures: The primary outcome was survival to hospital discharge. Secondary
      outcomes included return of spontaneous circulation and neurologic outcome. A
      favorable neurologic outcome was defined as a score of 1 to 2 on the pediatric
      cerebral performance category score. Patients being intubated at any given minute
      were matched with patients at risk of being intubated within the same minute (ie,
      still receiving resuscitation) based on a time-dependent propensity score
      calculated from multiple patient, event, and hospital characteristics. Results:
      The study included 2294 patients; 1308 (57%) were male, and all age groups were
      represented (median age, 7 months [25th-75th percentiles, 21 days, 4 years]). Of
      the 2294 included patients, 1555 (68%) were intubated during the cardiac arrest.
      In the propensity score-matched cohort (n = 2270), survival was lower in those
      intubated compared with those not intubated (411/1135 [36%] vs 460/1135 [41%];
      risk ratio [RR], 0.89 [95% CI, 0.81-0.99]; P = .03). There was no significant
      difference in return of spontaneous circulation (770/1135 [68%] vs 771/1135
      [68%]; RR, 1.00 [95% CI, 0.95-1.06]; P = .96) or favorable neurologic outcome
      (185/987 [19%] vs 211/983 [21%]; RR, 0.87 [95% CI, 0.75-1.02]; P = .08) between
      those intubated and not intubated. The association between intubation and
      decreased survival was observed in the majority of the sensitivity and subgroup
      analyses, including when accounting for missing data and in a subgroup of
      patients with a pulse at the beginning of the event. Conclusions and Relevance:
      Among pediatric patients with in-hospital cardiac arrest, tracheal intubation
      during cardiac arrest compared with no intubation was associated with decreased
      survival to hospital discharge. Although the study design does not eliminate the
      potential for confounding, these findings do not support the current emphasis on
      early tracheal intubation for pediatric in-hospital cardiac arrest.

PMID- 27701624
TI  - Work-Related Determinants of Voice Complaints Among School Workers: An Eleven
      Month Follow-Up Study.
AB  - Purpose: We determined the natural course of voice complaints among school
      workers and established the risk factors associated with incidence and chronic
      voice complaints. Method: We conducted a longitudinal study with an 11-month
      follow-up among 682 school workers. Participants filled out a questionnaire on
      individual and work-related conditions and the nature and severity of voice
      complaints. All participants who provided baseline data were contacted in the 11
      month follow-up, if they were still working in the school. Short-term
      environmental measurements of physical work-related factors were conducted during
      visits at the workplaces. Logistic regression analysis was used to determine
      associations between work-related factors and voice complaints. Results: We found
      a high occurrence of chronic voice complaints, a low recovery of 22%, and an
      annual incidence of 44%. A self-reported high noise level at the workplace was
      associated with the incidence of voice complaints (odds ratio = 2.45). Self
      reported poor acoustics in the classroom was associated with chronic voice
      complaints (odds ratio = 1.76). Conclusions: This unique longitudinal study among
      school workers presented some indications that self-reported high noise levels
      may contribute to the incidence of voice complaints, whereas self-reported poor
      acoustic conditions may be an important associated factor of chronic voice
      complaints.

PMID- 27701625
TI  - The Home Literacy Environment and the English Narrative Development of Spanish
      English Bilingual Children.
AB  - Purpose: The purpose of this study was to examine the impact of the home literacy
      environment (HLE) on the English narrative development of Spanish-English
      bilingual children from low-income backgrounds. Method: Longitudinal data were
      collected on 81 bilingual children from preschool through 1st grade. English
      narrative skills were assessed in the fall and spring of each year.
      Microstructure measures included mean length of utterance in morphemes and number
      of different words. The Narrative Scoring Scheme (Heilmann, Miller, Nockerts, &
      Dunaway, 2010) measured macrostructure. Each fall, the children's mothers
      reported the frequency of literacy activities and number of children's books in
      the home. Growth curve modeling was used to describe the children's narrative
      development and the impact of the HLE over time. Results: Significant growth
      occurred for all narrative measures. The HLE did not affect microstructure
      growth. The frequency with which mothers read to their children had a positive
      impact on the growth of the children's total Narrative Scoring Scheme scores.
      Other aspects of the HLE, such as the frequency with which the mothers told
      stories, did not affect macrostructure development. Conclusions: These results
      provide information about the development of English narrative abilities and
      demonstrate the importance of frequent book reading for the overall narrative
      quality of children from Spanish-speaking homes who are learning English.

PMID- 27701627
TI  - Special Issue: Spotlight of the Future of Cardiovascular Engineering Frontiers
      and Challenges in Cardiovascular Biomechanics.

PMID- 27701626
TI  - Gesture Use in 14-Month-Old Toddlers With Hearing Loss and Their Mothers'
      Responses.
AB  - Purpose: This study examined the gesture use of 14-month-old toddlers with
      hearing loss (HL) and mothers' responses to children's early gesture use.
      Comparisons were made to symbolic language and to dyads in which the toddler had
      normal hearing (NH). Method: Participants were 25 mother-toddler dyads in which
      the child had HL and a socioeconomic-status matched group of 23 mother-toddler
      dyads in which the child had NH. Thirty-minute mother-child interactions were
      video-recorded, transcribed for spoken language, sign, and gesture use, and coded
      for maternal responses to children's gestures. Mothers also reported on
      children's gestural and spoken language abilities. Results: Toddlers with HL used
      gesture similarly to their peers with NH, but demonstrated delays in spoken
      language. Spoken language and gesture were not significantly related for either
      group. Hearing levels were related to spoken language, but not gesture for the HL
      group. Maternal and child gesture were only related for signing mothers. Mothers
      of children with HL were more likely than their counterparts to provide no
      response to children's gestures. Conclusion: Although toddlers' gesture abilities
      remain intact in the presence of HL, mothers were not maximally responsive to
      those gestures and thus should be coached to increase their provision of
      contingent feedback.

PMID- 27701628
TI  - Effects of Biofeedback on Control and Generalization of Nasalization in Typical
      Speakers.
AB  - Purpose: The purpose of this study was to determine the effects of biofeedback on
      control of nasalization in individuals with typical speech. Method: Forty-eight
      individuals with typical speech attempted to increase and decrease vowel
      nasalization. During training, stimuli consisted of consonant-vowel-consonant
      (CVC) tokens with the center vowels /a/ or /i/ in either a nasal or nonnasal
      phonemic context (e.g., /mim/ vs. /bib/), depending on the participant's training
      group. Half of the participants had access to augmentative visual feedback during
      training, which was based on a less-invasive acoustic, accelerometric measure of
      vowel nasalization-the Horii oral-nasal coupling (HONC) score. During pre- and
      posttraining assessments, acoustically based nasalance was also measured from the
      center vowels /a/, /i/, /ae/, and /u/ of CVCs in both nasal and nonnasal
      contexts. Results: Linear regressions indicated that both phonemic contexts
      (nasal or nonnasal) and the presence of augmentative visual feedback during
      training were significant predictors for changes in nasalance scores from pre- to
      posttraining. Conclusions: Participants were able to change the nasalization of
      their speech following a training period with HONC biofeedback. Future work is
      necessary to examine the effect of such training in individuals with
      velopharyngeal dysfunction.

PMID- 27701629
TI  - Dose Schedule and Enhanced Conversational Recast Treatment for Children With
      Specific Language Impairment.
AB  - Purpose: Dosage has been identified as an important element of treatment that may
      affect treatment efficacy. The purpose of this study was to examine the role of
      dose schedule for treatment of grammatical morphology deficits in children with
      specific language impairment (SLI). Method: Sixteen 4-to-5-year-old children with
      SLI participated in a 5-week intervention consisting of equivalent daily Enhanced
      Conversational Recast treatment (Plante et al., 2014) targeting grammatical
      morphology. Half of the children received treatment in one 30-min session (massed
      condition). Half received treatment in three 10-min sessions (spaced condition)
      within one 4-hr period. Progress was assessed 3 times weekly by probing a child's
      use of his or her treatment morpheme and untreated morpheme (a maturational
      control) in untreated contexts. Results: Pre- to posttreatment morpheme usage
      differed significantly for children regardless of dosage condition, and pre to
      post usage of an untreated morpheme was unchanged, demonstrating overall
      treatment efficacy. There were no differences in treatment effects for the massed
      and spaced conditions. Conclusions: The study adds to evidence that Enhanced
      Conversational Recast can produce positive results in a short period of time for
      children with SLI. Furthermore, clinicians may have some flexibility in terms of
      the dose schedule they use to deliver this treatment in an evidence-based manner.

PMID- 27701631
TI  - Improved Automated Detection of Diabetic Retinopathy on a Publicly Available
      Dataset Through Integration of Deep Learning.
AB  - Purpose: To compare performance of a deep-learning enhanced algorithm for
      automated detection of diabetic retinopathy (DR), to the previously published
      performance of that algorithm, the Iowa Detection Program (IDP)-without deep
      learning components-on the same publicly available set of fundus images and
      previously reported consensus reference standard set, by three US Board certified
      retinal specialists. Methods: We used the previously reported consensus reference
      standard of referable DR (rDR), defined as International Clinical Classification
      of Diabetic Retinopathy moderate, severe nonproliferative (NPDR), proliferative
      DR, and/or macular edema (ME). Neither Messidor-2 images, nor the three retinal
      specialists setting the Messidor-2 reference standard were used for training IDx
      DR version X2.1. Sensitivity, specificity, negative predictive value, area under
      the curve (AUC), and their confidence intervals (CIs) were calculated. Results:
      Sensitivity was 96.8% (95% CI: 93.3%-98.8%), specificity was 87.0% (95% CI: 84.2%
      89.4%), with 6/874 false negatives, resulting in a negative predictive value of
      99.0% (95% CI: 97.8%-99.6%). No cases of severe NPDR, PDR, or ME were missed. The
      AUC was 0.980 (95% CI: 0.968-0.992). Sensitivity was not statistically different
      from published IDP sensitivity, which had a CI of 94.4% to 99.3%, but specificity
      was significantly better than the published IDP specificity CI of 55.7% to 63.0%.
      Conclusions: A deep-learning enhanced algorithm for the automated detection of
      DR, achieves significantly better performance than a previously reported,
      otherwise essentially identical, algorithm that does not employ deep learning.
      Deep learning enhanced algorithms have the potential to improve the efficiency of
      DR screening, and thereby to prevent visual loss and blindness from this
      devastating disease.

PMID- 27701630
TI  - Lentiviral Delivery of Small Hairpin RNA Targeting Connective Tissue Growth
      Factor Blocks Profibrotic Signaling in Tenon's Capsule Fibroblasts.
AB  - Purposes: Trabeculectomy is a surgical procedure for lowering intraocular
      pressure in glaucoma patients, in which excessive scarring leading to failure of
      the filtering bleb adversely affects the surgical outcome. Heightened Tenon's
      capsule fibroblast (TCF) proliferation and extracellular matrix (ECM) deposition
      are implicated in this process but endogenous factors that regulate TCF functions
      remain largely elusive. This study sought to elucidate the role of connective
      tissue growth factor (CTGF) in the regulation of TCF phenotypes and signaling.
      Methods: Expression of CTGF in scarring and nonscarring Tenon's capsules was
      measured by real-time PCR and immunofluorescence. Knockdown of CTGC was achieved
      by lentivirus delivery of small-hairpin RNA. Cell proliferation was measured by
      CCK8, cell cycle progression, and apoptosis by flow cytometry, adhesion,
      migration, and invasion of TCF by functional assays in vitro. Proteins and
      cytokines related to fibrosis were measured by Western blot and ELISA,
      respectively. Results: Expression of CTGF was significantly upregulated in
      scarring Tenon's capsules and their isolated fibroblasts when compared with the
      nonfibrotic counterparts. Functionally, targeting CTGF with lentivirus-delivered
      small-hairpin RNA inhibited the proliferation, adhesion, migration, and invasion
      of TCFs, accompanied by downregulation of p38 and nuclear factor-kappaB as well
      as matrix metalloproteinase-2, cyclin D1, and collagen I. In addition, lentiviral
      targeting of CTGF reduced the release of fibrosis-related cytokines from TCFs and
      inhibited TCF-conditioned, medium-induced macrophage chemotaxis. Conclusions: Our
      study supports a crucial role of CTGF in the regulation of TCF proliferation and
      ECM deposition. Targeting CTGF using lentiviral vector may be a promising
      approach for preventing excessive scarring after trabeculectomy.

PMID- 27701632
TI  - An In Vitro Perfusion System to Enhance Outflow Studies in Mouse Eyes.
AB  - Purpose: The molecular mechanisms controlling aqueous humor (AQH) outflow and IOP
      need much further definition. The mouse is a powerful system for characterizing
      the mechanistic basis of AQH outflow. To enhance outflow studies in mice, we
      developed a perfusion system that is based on human anterior chamber perfusion
      culture systems. Our mouse system permits previously impractical experiments.
      Methods: We engineered a computer-controlled, pump-based perfusion system with a
      platform for mounting whole dissected mouse eyes (minus lens and iris, ~45% of
      drainage tissue is perfused). We tested the system's ability to monitor outflow
      and tested the effects of the outflow-elevating drug, Y27632, a rho-associated
      protein kinase (ROCK) inhibitor. Finally, we tested the system's ability to
      detect genetically determined decreases in outflow by determining if deficiency
      of the candidate genes Nos3 and Cav1 alter outflow. Results: Using our system,
      the outflow facility (C) of C57BL/6J mouse eyes was found to range between 7.7
      and 10.4 nl/minutes/mm Hg (corrected for whole eye). Our system readily detected
      a 74.4% Y27632-induced increase in C. The NOS3 inhibitor L-NG-nitroarginine
      methyl ester (L-NAME) and a Nos3 null mutation reduced C by 28.3% and 35.8%,
      respectively. Similarly, in Cav1 null eyes C was reduced by 47.8%. Conclusions:
      We engineered a unique perfusion system that can accurately measure changes in C.
      We then used the system to show that NOS3 and CAV1 are key components of
      mechanism(s) controlling outflow.

PMID- 27701633
TI  - Stimulation of a Suprachoroidal Retinal Prosthesis Drives Cortical Responses in a
      Feline Model of Retinal Degeneration.
AB  - Purpose: Retinal prostheses have emerged as a promising technology to restore
      vision in patients with severe photoreceptor degeneration. To better understand
      how neural degeneration affects the efficacy of electronic implants, we
      investigated the function of a suprachoroidal retinal implant in a feline model.
      Methods: Unilateral retinal degeneration was induced in four adult felines by
      intravitreal injection of adenosine triphosphate (ATP). Twelve weeks post
      injection, animals received suprachoroidal electrode array implants in each eye,
      and responses to electrical stimulation were obtained using multiunit recordings
      from the visual cortex. Histologic measurements of neural and glial changes in
      the retina at the implant site were correlated with cortical thresholds from
      individual stimulating electrodes. Results: Adenosine triphosphate-injected eyes
      displayed changes consistent with mid-to-late stage retinal degeneration and
      remodeling. A significant increase in electrical charge was required to induce a
      cortical response from stimulation of the degenerated retina compared to that in
      the fellow control eye. Spatial and temporal characteristics of the electrically
      evoked cortical responses were no different between eyes. Individual electrode
      thresholds varied in both the control and the ATP-injected eyes and were
      correlated with ganglion cell density. In ATP-injected eyes, cortical threshold
      was also independently correlated with an increase in the extent of retinal
      gliosis. Conclusions: These data suggest that even when ganglion cell density
      remains unaffected, glial changes in the retina following degeneration can
      influence the efficacy of suprachoroidal electrical stimulation. A better
      understanding of how glial change impacts retinal prosthesis function may help to
      further the optimization of retinal implants.

PMID- 27701634
TI  - Myopia and Cognitive Performance: Results From the Gutenberg Health Study.
AB  - Purpose: To analyze the association between myopia and cognitive performance.
      Methods: A cohort of the population-based Gutenberg Health Study included 3819
      eligible enrollees between 40 and 79 years. We used the Tower of London (TOL)
      test to assess cognitive performance. Myopia was defined as a spherical
      equivalent (SE) <= -0.5 diopters (D) via noncycloplegic autorefractometry. We
      conducted linear mixed models with the SE as the dependent variable and the age,
      sex, duration of education, and TOL score as covariates. Results: Complete data
      were available for 3452 participants (90.4%). The mean TOL score was 14.0 +/- 3.9
      in the myopes versus 12.9 +/- 4.0 in the nonmyopes (P < 0.001). The mean TOL
      score increased with the magnitude of myopia: it was 13.9 +/- 3.9 in low (less
      than -3 D); 14.2 +/- 3.7 in moderate (between -3 and -6 D); and 14.6 +/- 3.5 in
      high myopia (-6 D and greater; P < 0.001). Both the duration of education and
      cognitive performance were correlated with the magnitude of myopia (r = -0.21, P
      < 0.001 and r = -0.15, P < 0.001, respectively). In a linear mixed model, the
      duration of education significantly predicted myopia (beta = -0.14; t = -7.55; P
      < 0.001), whereas cognitive performance did not (beta = -0.017; t = -1.26; P =
      0.207). There was a significant effect of age on the SE (beta = 0.049; t = 9.89;
      P < 0.001). Conclusions: When regarded separately, cognitive performance is
      linked to myopia. However, duration of education, which may be directly related
      to the risk factors for myopia, is more directly and strongly related to myopia
      than is cognitive performance. Cognitive ability may be associated with myopia
      primarily through its impact on level of education.

PMID- 27701635
TI  - The Role of IRE-XBP1 Pathway in Regulation of Retinal Pigment Epithelium Tight
      Junctions.
AB  - Purpose: The retinal pigment epithelium (RPE) tight junctions play a pivotal role
      in maintaining the homeostatic environment of the neural retina. Herein, we
      investigated the role of X-box binding protein 1 (XBP1), an endoplasmic reticulum
      (ER) stress-responsive transcription factor, in regulation of RPE tight
      junctions. Methods: Human RPE cell line (ARPE-19) and primary primate RPE cells
      were used for in vitro experiments and RPE-specific XBP1 knockout (KO) mice were
      used for in vivo study. Endoplasmic reticulum stress was induced by a sublethal
      dose of thapsigargin or tunicamycin. XBP1 activation was manipulated by IRE
      inhibitor 4MU8C, which suppresses XBP1 mRNA splicing. The integrity of tight
      junctions and the involvement of calcium-dependent RhoA/Rho kinase pathway were
      examined. Results: Induction of ER stress by thapsigargin, but not tunicamycin,
      disrupted RPE tight junctions in ARPE-19 cells. Inhibition of XBP1 activation by
      4MU8C resulted in a remarkable downregulation of tight junction proteins (ZO-1
      and occludin) and defects in tight junction formation in the presence or absence
      of ER stress inducers. Overexpression of active XBP1 partially reversed 4MU8C
      induced anomalies in tight junctions. Mechanistically, XBP1 inhibition resulted
      in increased intracellular Ca2+ concentration, upregulation of RhoA expression,
      redistribution of F-actin, and tight junction damage, which was attenuated by Rho
      kinase inhibitor Y27632. In vivo, deletion of XBP1 in the RPE resulted in
      defective RPE tight junctions accompanied by increased VEGF expression.
      Conclusions: Taken together, these results suggest a protective role of XBP1 in
      maintaining RPE tight junctions possibly through regulation of calcium-dependent
      RhoA/Rho kinase signaling and actin cytoskeletal reorganization.

PMID- 27701637
TI  - Anterior Corneal, Posterior Corneal, and Lenticular Contributions to Ocular
      Aberrations.
AB  - Purpose: To determine the corneal surfaces and lens contributions to ocular
      aberrations. Methods: There were 61 healthy participants with ages ranging from
      20 to 55 years and refractions -8.25 diopters (D) to +3.25 D. Anterior and
      posterior corneal topographies were obtained with an Oculus Pentacam, and ocular
      aberrations were obtained with an iTrace aberrometer. Raytracing through models
      of corneas provided total corneal and surface component aberrations for 5-mm
      diameter pupils. Lenticular contributions were given as differences between
      ocular and corneal aberrations. Theoretical raytracing investigated influence of
      object distance on aberrations. Results: Apart from defocus, the highest
      aberration coefficients were horizontal astigmatism, horizontal coma, and
      spherical aberration. Most correlations between lenticular and ocular parameters
      were positive and significant, with compensation of total corneal aberrations by
      lenticular aberrations for 5/12 coefficients. Anterior corneal aberrations were
      approximately three times higher than posterior corneal aberrations and usually
      had opposite signs. Corneal topographic centers were displaced from aberrometer
      pupil centers by 0.32 +/- 0.19 mm nasally and 0.02 +/- 0.16 mm inferiorly;
      disregarding corneal decentration relative to pupil center was significant for
      oblique astigmatism, horizontal coma, and horizontal trefoil. An object at
      infinity, rather than at the image in the anterior cornea, gave incorrect
      aberration estimates of the posterior cornea. Conclusions: Corneal and lenticular
      aberration magnitudes are similar, and aberrations of the anterior corneal
      surface are approximately three times those of the posterior surface. Corneal
      decentration relative to pupil center has significant effects on oblique
      astigmatism, horizontal coma, and horizontal trefoil. When estimating component
      aberrations, it is important to use correct object/image conjugates and heights
      at surfaces.

PMID- 27701636
TI  - Loss of Axin2 Causes Ocular Defects During Mouse Eye Development.
AB  - Purpose: The scaffold protein Axin2 is an antagonist and universal target of the
      Wnt/beta-catenin pathway. Disruption of Axin2 may lead to developmental eye
      defects; however, this has not been examined. The purpose of this study was to
      investigate the role of Axin2 during ocular and extraocular development in mouse.
      Methods: Animals heterozygous and homozygous for a Axin2lacZ knock-in allele were
      analyzed at different developmental stages for reporter expression, morphology as
      well as for the presence of ocular and extraocular markers using histologic and
      immunohistochemical techniques. Results: During early eye development, the
      Axin2lacZ reporter was expressed in the periocular mesenchyme, RPE, and optic
      stalk. In the developing retina, Axin2lacZ reporter expression was initiated in
      ganglion cells at late embryonic stages and robustly expressed in subpopulations
      of amacrine and horizontal cells postnatally. Activation of the Axin2lacZ
      reporter overlapped with labeling of POU4F1, PAX6, and Calbindin. Germline
      deletion of Axin2 led to variable ocular phenotypes ranging from normal to
      severely defective eyes exhibiting microphthalmia, coloboma, lens defects, and
      expanded ciliary margin. These defects were correlated with abnormal tissue
      patterning in individual affected tissues, such as the optic fissure margins in
      the ventral optic cup and in the expanded ciliary margin. Conclusions: Our
      results reveal a critical role for Axin2 during ocular development, likely by
      restricting the activity of the Wnt/beta-catenin pathway.

PMID- 27701639
TI  - Error in Table Row Alignment and No. of Participants.

PMID- 27701638
TI  - What's in Your Library?: "The Leaven of the Humanities".

PMID- 27701640
TI  - Introducing The Arts and Medicine: JAMA Turns Another Page.

PMID- 27701641
TI  - Avoiding Open-Heart Surgery.

PMID- 27701642
TI  - Evaluating Patients for Concussion.

PMID- 27701643
TI  - Programmable Syringe Pump Alert.

PMID- 27701644
TI  - Management of Acne Vulgaris.

PMID- 27701646
TI  - Why Are Private Health Insurers Losing Money on Obamacare?

PMID- 27701647
TI  - The Lower Animals and Human Disease.

PMID- 27701648
TI  - Imaging Epigenetics in the Human Brain.

PMID- 27701649
TI  - How Oral Microbes Exacerbate Colorectal Cancer.

PMID- 27701650
TI  - Reservoir of Genetic Data Related to Cardiovascular Disease.

PMID- 27701651
TI  - Primary Care "Provider" and Professional Identity.

PMID- 27701652
TI  - Primary Care "Provider" and Professional Identity.

PMID- 27701653
TI  - Radiation Therapy Deviations in Trial of Locally Advanced Pancreatic Cancer
      [corrected].

PMID- 27701654
TI  - Improving the Physical Examination.

PMID- 27701655
TI  - Radiation Therapy Deviations in Trial of Locally Advanced Prostate Cancer-Reply.

PMID- 27701656
TI  - Primary Care "Provider" and Professional Identity-Reply.

PMID- 27701657
TI  - Improving the Physical Examination-Reply.

PMID- 27701658
TI  - Alternatives to Fluoroquinolones.

PMID- 27701659
TI  - Association Between Therapeutic Hypothermia and Survival After In-Hospital
      Cardiac Arrest.
AB  - Importance: Therapeutic hypothermia is used for patients following both out-of
      hospital and in-hospital cardiac arrest. However, randomized trials on its
      efficacy for the in-hospital setting do not exist, and comparative effectiveness
      data are limited. Objective: To evaluate the association between therapeutic
      hypothermia and survival after in-hospital cardiac arrest. Design, Setting, and
      Patients: In this cohort study, within the national Get With the Guidelines
      Resuscitation registry, 26 183 patients successfully resuscitated from an in
      hospital cardiac arrest between March 1, 2002, and December 31, 2014, and either
      treated or not treated with hypothermia at 355 US hospitals were identified.
      Follow-up ended February 4, 2015. Exposure: Induction of therapeutic hypothermia.
      Main Outcomes and Measures: The primary outcome was survival to hospital
      discharge. The secondary outcome was favorable neurological survival, defined as
      a Cerebral Performance Category score of 1 or 2 (ie, without severe neurological
      disability). Comparisons were performed using a matched propensity score analysis
      and examined for all cardiac arrests and separately for nonshockable (asystole
      and pulseless electrical activity) and shockable (ventricular fibrillation and
      pulseless ventricular tachycardia) cardiac arrests. Results: Overall, 1568 of 26
      183 patients with in-hospital cardiac arrest (6.0%) were treated with therapeutic
      hypothermia; 1524 of these patients (mean [SD] age, 61.6 [16.2] years; 58.5%
      male) were matched by propensity score to 3714 non-hypothermia-treated patients
      (mean [SD] age, 62.2 [17.5] years; 57.1% male). After adjustment, therapeutic
      hypothermia was associated with lower in-hospital survival (27.4% vs 29.2%;
      relative risk [RR], 0.88 [95% CI, 0.80 to 0.97]; risk difference, -3.6% [95% CI, 
      6.3% to -0.9%]; P = .01), and this association was similar (interaction P = .74)
      for nonshockable cardiac arrest rhythms (22.2% vs 24.5%; RR, 0.87 [95% CI, 0.76
      to 0.99]; risk difference, -3.2% [95% CI, -6.2% to -0.3%]) and shockable cardiac
      arrest rhythms (41.3% vs 44.1%; RR, 0.90 [95% CI, 0.77 to 1.05]; risk difference,
      -4.6% [95% CI, -10.9% to 1.7%]). Therapeutic hypothermia was also associated with
      lower rates of favorable neurological survival for the overall cohort
      (hypothermia-treated group, 17.0% [246 of 1443 patients]; non-hypothermia-treated
      group, 20.5% [725 of 3529 patients]; RR, 0.79 [95% CI, 0.69 to 0.90]; risk
      difference, -4.4% [95% CI, -6.8% to -2.0%]; P < .001) and for both rhythm types
      (interaction P = .88). Conclusions and Relevance: Among patients with in-hospital
      cardiac arrest, use of therapeutic hypothermia compared with usual care was
      associated with a lower likelihood of survival to hospital discharge and a lower
      likelihood of favorable neurological survival. These observational findings
      warrant a randomized clinical trial to assess efficacy of therapeutic hypothermia
      for in-hospital cardiac arrest.

PMID- 27701661
TI  - OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary
      Incontinence in Women: A Randomized Clinical Trial.
AB  - Importance: Women with refractory urgency urinary incontinence are treated with
      sacral neuromodulation and onabotulinumtoxinA with limited comparative
      information. Objective: To assess whether onabotulinumtoxinA is superior to
      sacral neuromodulation in controlling refractory episodes of urgency urinary
      incontinence. Design, Setting, and Participants: Multicenter open-label
      randomized trial (February 2012-January 2015) at 9 US medical centers involving
      381 women with refractory urgency urinary incontinence. Interventions:
      Cystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or
      sacral neuromodulation (n = 189). Main Outcomes and Measures: Primary outcome,
      change from baseline mean number of daily urgency urinary incontinence episodes
      over 6 months, was measured with monthly 3-day diaries. Secondary outcomes
      included change from baseline in urinary symptom scores in the Overactive Bladder
      Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse
      symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5
      subscales, higher scores indicating better satisfaction; and adverse events.
      Results: Of the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to
      treat population, 190 women in the onabotulinumtoxinA group had a greater
      reduction in 6-month mean number of episodes of urgency incontinence per day than
      did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day;
      mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with
      onabotulinumtoxinA showed greater improvement in the Overactive Bladder
      Questionnaire SF for symptom bother (-46.7 vs -38.6; mean difference, 8.1; 95%
      CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean
      difference, 7.8; 95% CI, 1.6 to 14.1; P = .01) and treatment endorsement (78.1 vs
      67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with
      sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2;
      mean difference, -2.5; 95% CI, -8.1 to 3.0; P = .36), adverse effects (88.4 vs
      85.1; mean difference, 3.3; 95% CI, -1.9 to 8.5; P = .22), and treatment
      preference (92.% vs 89%; risk difference, -3%; 95% CI, -16% to 10%; P = .49).
      Urinary tract infections were more frequent in the onabotulinumtoxinA group (35%
      vs 11%; risk difference, -23%; 95% CI, -33% to -13%; P < .001). The need for self
      catheterization was 8% and 2% at 1 and 6 months in the onabotulinumtoxinA group.
      Neuromodulation device revisions and removals occurred in 3%. Conclusions and
      Relevance: Among women with refractory urgency urinary incontinence, treatment
      with onabotulinumtoxinA compared with sacral neuromodulation resulted in a small
      daily improvement in episodes that although statistically significant is of
      uncertain clinical importance. In addition, it resulted in a higher risk of
      urinary tract infections and need for transient self-catheterizations.

PMID- 27701662
TI  - Treatments for Nausea and Vomiting During Pregnancy.

PMID- 27701664
TI  - The Quick Physical Exam.

PMID- 27701660
TI  - Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants
      and Risk of Type 2 Diabetes: A Meta-analysis.
AB  - Importance: Low-density lipoprotein cholesterol (LDL-C)-lowering alleles in or
      near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and
      statins, have previously been used as proxies to study the efficacy of these
      lipid-lowering drugs. Alleles near HMGCR are associated with a higher risk of
      type 2 diabetes, similar to the increased incidence of new-onset diabetes
      associated with statin treatment in randomized clinical trials. It is unknown
      whether alleles near NPC1L1 are associated with the risk of type 2 diabetes.
      Objective: To investigate whether LDL-C-lowering alleles in or near NPC1L1 and
      other genes encoding current or prospective molecular targets of lipid-lowering
      therapy (ie, HMGCR, PCSK9, ABCG5/G8, LDLR) are associated with the risk of type 2
      diabetes. Design, Setting, and Participants: The associations with type 2
      diabetes and coronary artery disease of LDL-C-lowering genetic variants were
      investigated in meta-analyses of genetic association studies. Meta-analyses
      included 50 775 individuals with type 2 diabetes and 270 269 controls and 60 801
      individuals with coronary artery disease and 123 504 controls. Data collection
      took place in Europe and the United States between 1991 and 2016. Exposures: Low
      density lipoprotein cholesterol-lowering alleles in or near NPC1L1, HMGCR, PCSK9,
      ABCG5/G8, and LDLR. Main Outcomes and Measures: Odds ratios (ORs) for type 2
      diabetes and coronary artery disease. Results: Low-density lipoprotein
      cholesterol-lowering genetic variants at NPC1L1 were inversely associated with
      coronary artery disease (OR for a genetically predicted 1-mmol/L [38.7-mg/dL]
      reduction in LDL-C of 0.61 [95% CI, 0.42-0.88]; P = .008) and directly associated
      with type 2 diabetes (OR for a genetically predicted 1-mmol/L reduction in LDL-C
      of 2.42 [95% CI, 1.70-3.43]; P < .001). For PCSK9 genetic variants, the OR for
      type 2 diabetes per 1-mmol/L genetically predicted reduction in LDL-C was 1.19
      (95% CI, 1.02-1.38; P = .03). For a given reduction in LDL-C, genetic variants
      were associated with a similar reduction in coronary artery disease risk (I2 = 0%
      for heterogeneity in genetic associations; P = .93). However, associations with
      type 2 diabetes were heterogeneous (I2 = 77.2%; P = .002), indicating gene
      specific associations with metabolic risk of LDL-C-lowering alleles. Conclusions
      and Relevance: In this meta-analysis, exposure to LDL-C-lowering genetic variants
      in or near NPC1L1 and other genes was associated with a higher risk of type 2
      diabetes. These data provide insights into potential adverse effects of LDL-C
      lowering therapy.

PMID- 27701665
TI  - Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A
      Systematic Review.
AB  - Importance: Nausea and vomiting affects approximately 85% of pregnant women. The
      most severe form, hyperemesis gravidarum, affects up to 3% of women and can have
      significant adverse physical and psychological sequelae. Objective: To summarize
      current evidence on effective treatments for nausea and vomiting in pregnancy and
      hyperemesis gravidarum. Evidence Review: Databases were searched to June 8, 2016.
      Relevant websites and bibliographies were also searched. Titles and abstracts
      were assessed independently by 2 reviewers. Results were narratively synthesized;
      planned meta-analysis was not possible because of heterogeneity and incomplete
      reporting of findings. Findings: Seventy-eight studies (n  = 8930 participants)
      were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies.
      Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6,
      antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and
      ondansetron (for moderate symptoms) were associated with improved symptoms
      compared with placebo. One RCT (n = 86) reported greater improvements in moderate
      symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms}
      to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for
      intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]).
      For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine
      combination taken preemptively reduced risk of recurrence of moderate-severe
      symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]).
      One RCT (n = 83) found that ondansetron was associated with lower nausea scores
      on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9]
      for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes
      of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there
      was no difference in trend in nausea scores over the 14-day study period, trend
      in vomiting scores was better in the ondansetron group (P = .042). One RCT (n =
      159) found no difference between metoclopramide and promethazine after 24 hours
      (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for
      promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1
      4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or
      promethazine or metoclopramide in women with severe symptoms. Improvements were
      seen in all corticosteroid groups, but only a significant difference between
      corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5%
      at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]).
      For other interventions, evidence was limited. Conclusions and Relevance: For
      mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine,
      antihistamines, and metoclopramide were associated with greater benefit than
      placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and
      metoclopramide were associated with greater benefit than placebo. Ondansetron was
      associated with improvement for a range of symptom severity. Corticosteroids may
      be associated with benefit in severe cases. Overall the quality of evidence was
      low.

PMID- 27701667
TI  - Changing the Language of Addiction.

PMID- 27701668
TI  - CD1c+ Blood Dendritic Cells in Atopic Dermatitis are Premature and Can Produce
      Disease-specific Chemokines.
AB  - Skin dendritic cells of patients with atopic dermatitis (AD) are well
      characterized, but less is known about their peripheral blood precursors. The aim
      of this study was to investigate the phenotypic features and chemokine production
      of myeloid pre-dendritic cells of patients with AD ex vivo and after stimulation
      with Staphylococcus enterotoxin B and thymic stromal lymphopoietin, representing
      an AD-like microenvironment. The expression of cell surface markers was measured
      by flow cytometry, while chemokine production was monitored with chemokine
      antibody array and confirmed by enzyme-linked immunoassays. AD pre-dendritic
      cells expressed higher levels of Fc?RI and the maturation and activation markers
      tended to be altered. They produced both AD (CCL17/18/22) and maturation-related
      (CCL3/4/5) chemokines at higher level than controls. The production of CCL3/4 and
      CCL18 were significantly higher even without AD-specific stimulation, while the
      production of CCL17 and CCL22 were significantly higher only after stimulation.
      These results indicate that circulating AD pre-dendritic cells are premature and
      bear atopic characteristics even without tissue-specific stimulation, suggesting
      that their development is not only influenced by the skin microenvironment, but
      even earlier by the local milieu in the blood.

PMID- 27701669
TI  - Assessing the Concordance of Actinic Keratosis Counts on Digital Photographs with
      Clinical Examination in Organ Transplant Recipients.
AB  - Actinic keratoses (AKs) are common lesions that are usually diagnosed clinically.
      We sought to examine the accuracy of AK counts on digital photographs when
      compared with clinical examination counts. Skin sites of renal transplant
      recipients were examined clinically and on digital photographs by independent
      dermatologically-trained examiners. Specificity, sensitivity and Kendall's tau-b
      correlation coefficient were calculated based on exact photographic AK counts as
      well as counts with +/- 1 AK tolerance. When 138 skin sites with 305 clinical AK
      counts were examined for total count +/- 1 AK, the sensitivity and specificity of
      photography was 95% and 100%, respectively. There was significant positive
      correlation between AK counts on photographs and clinical examination (Tb =
      0.537) and correlation was even higher for total count +/- 1 AK (Tb = 0.758). The
      results show moderate to strong concordance between AK counts on digital
      photographs and on clinical examination.

PMID- 27701670
TI  - Annular Eruptive Pseudoangiomatosis and Adenovirus Infection: A Novel Clinical
      Variant of Paraviral Exanthems and a Novel Virus Association.
AB  - Eruptive pseudoangiomatosis is a distinct exanthem thought to be caused by
      viruses. The usual rash configu-ration is erythematous papules and macules. An
      association with echovirus infection has been reported. We present here one adult
      and one child with this exanthem, supported by clinical, histopathological, and
      immunohistochemical findings. Both patients presented with prodromal symptoms,
      widespread angioma-like macules in annular configuration, blanchable
      telangiectasia, followed by spontaneous remission in 6-8 weeks. Lesional
      histopathology of the adult patient revealed dilated dermal blood vessels and
      lymphohistiocytic infiltrates predominated by CD4+ lymphocytes with a 5:1 ratio
      of CD4:CD8 lymphocytes. No B cells or CD56+ natural killer cells were found.
      Serology of both patients revealed evidence of active infections by adenoviruses,
      and a range of other viruses were excluded. We believe that these 2 patients
      manifested annular eruptive pseudoangio-matosis, a novel variant of the rash with
      a probable adenovirus association that has not yet been reported.

PMID- 27701671
TI  - [Shoulder dislocation].

PMID- 27701672
TI  - [Survey of early alcohol treatment preferences shows higher confidence in face to
      face meetings].
AB  - Survey of early alcohol  treatment preferences shows higher confidence in face to
      face meetings Adult men and women (n = 307), working and living in the area of
      south west Sweden, answered a web based questionnaire where they graded treatment
      and caregiver preferences while imagining themselves developing an alcohol
      problem. Alcohol consumption was measured using AUDIT-C. Face-to-face delivered
      treatment was preferred over telephone or internet based advice. About 53 percent
      of the men and women considered treatment given by primary health as poor. Only
      7,6 percent would prefer help from a health care centre if they were having
      alcohol problems. Shame and stigma were considered the main obstacles for both
      seeking and getting help. Despite the availability of effective treatments for
      early alcohol problems, many avoid seeking help for their problem. This also
      applies to socially established people. It is important that the health care
      recognizes and identifies people with less serious problems and offer them
      treatment.

PMID- 27701673
TI  - [Good prognosis for alcohol addiction, but few seek treatment. Today's dependence
      policies are stereotypical and outdated - primary health care could give good
      treatment].

PMID- 27701674
TI  - [Congenital alcohol injuries should be identified in schools].

PMID- 27701675
TI  - [The influx of deadly internet drugs continue].

PMID- 27701676
TI  - [Reasonable use of language called for].

PMID- 27701677
TI  - [Progress in the work against tuberculosis in Syria needs to be nurtured].

PMID- 27701678
TI  - [Research gray area].

PMID- 27701679
TI  - [The fatal blow to residency in Aland].

PMID- 27701680
TI  - [Urolithiasis in the Long-Term GnRH Agonist Treatment of Patients with
      Paraphilia: 3 Case Studies].
AB  - The outpatient forensic aftercare department of the Charite Berlin treated 32
      paraphilic sex offenders with GnRH analogues within the past 5 years. Out of
      those patients, three men suffered from urolithiasis and were in need of
      treatment. All 3 patients had previously developed osteopenia/osteoporosis while
      on antiandrogen treatment.This article describes these 3 cases and suggests an
      intense consideration of the possible occurrence of urolithiasis in sex offenders
      on antiandrogen treatment.

PMID- 27701681
TI  - Long-Term Health Outcomes and Health-Related Quality of Life in Adolescents from
      a Cohort of Extremely Premature Infants Born at Less Than 27 Weeks of Gestation
      in Northern Germany.
AB  - Background Little is known about the psychosocial development and health-related
      quality of life (HRQOL) of extremely preterm infants once they are adolescents.
      Methods The regional population-based study cohort included 90 extremely
      premature infants (< 27+0 gestational weeks) born between January 1997 and
      December 1999 in the German state of Schleswig-Holstein. In addition to a
      neurological and cognitive Wechsler Intelligence Scale for Children, 4th edition
      assessment, self- and parent-reported psychological problems (Strengths and
      Difficulties Questionnaire), and health-related quality of life (KINDLR) were
      obtained and compared with a general population of 3,737 adolescents using data
      from a German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS survey 2003-2006, Robert Koch Institute, Germany). Results
      Overall, 72 of the 90 surviving adolescents and their families (80.0%)
      participated in this study (mean age: 15.7 years; range: 14.2-17.2). A total of
      22 adolescents (30.6%) did not have any neurosensory or cognitive limitations,
      whereas 31 adolescents (43.1%) were affected by multiple impairments. Parent
      reported psychological problems were more common in the study cohort for the
      total difficulties score (11.3 points [standard deviation, SD: 5.9] vs. 7.7
      points [SD: 5.0], p < 0.001) and for three of the five domains (emotional
      symptoms, hyperactivity-inattention, peer relationship problems) compared with
      the KiGGS reference population. In contrast, the rate of self-reported "abnormal"
      psychological problems was similar to the reference population. Parent-reported
      HRQOL was significantly lower in the study cohort for the total score (-3.7
      points, p < 0.05) and for three of six subscales (emotional wellbeing, p < 0.05;
      self-esteem, p < 0.001, and wellbeing with regard to friends/friendship, p <
      0.001). The adolescents themselves reported an HRQOL similar to that of the KiGGS
      reference population, though they rated their HRQOL higher for wellbeing with
      regard to families (p < 0.001) and wellbeing with regard to school/all-day
      function (p < 0.001). Overall, the parent- and self-reported HRQOL results were
      not associated with maternal education or disability status but were associated
      with adolescents' psychological problems. Conclusion Concordant with the high
      rate of functional and cognitive limitations, parents of adolescents who were
      born extremely prematurely faced more psychological problems in their children
      and reported a lower HRQOL compared with the KiGGS reference population. The
      adolescents themselves did not recognize these differences. However, having
      psychological problems was associated with lower self- and parent-reported HRQOL
      results.

PMID- 27701682
TI  - Ghrelin, Ghrelin O-Acyltransferase, and Carbohydrate Metabolism During Pregnancy
      in Calorie-Restricted Mice.
AB  - Acylation of ghrelin is mediated by ghrelin O-acyltansferase (GOAT). Exogenous
      acylated ghrelin (AG) stimulates growth hormone (GH) and food intake. In non
      pregnant (NP) animals, the GOAT-ghrelin-GH axis prevents hypoglycemia caused by
      caloric restriction (CR). In humans, maternal malnutrition challenges glucose
      metabolism, which is a key determinant of fetal health. To clarify the role of AG
      and GH, we compared effects of CR on the GOAT-ghrelin-GH axis in pregnant (P) and
      NP mice. C57BL/6 wild type (WT) and GOAT knock-out (KO) P and NP mice were freely
      fed (FF) or subjected to 50% CR for one week. CR was started in P mice on Day
      10.5 after conception. We measured body composition, blood glucose, plasma
      ghrelin and GH, stomach, hypothalamus and pituitary GOAT and ghrelin expression,
      and liver glycogen content and Pck1 expression. GOAT and AG were undetectable in
      KO. In NP mice, CR did not affect blood glucose (-1.3 mmol/l, p>0.05) in WT but
      was lowered (-1.8 mmol/l, p<0.0001) in KO. GH and Pck1 mRNA expression increased
      in WT but not in KO. In P mice, CR markedly lowered glucose (-2.7 mmol/l;
      p<0.0001) in WT and caused fatal hypoglycemia in KO, despite similarly elevated
      GH in WT and KO mice. KO animals are more prone to hypoglycemia than WT. GH,
      which is high in P animals, does not prevent hypoglycemia caused by CR during
      pregnancy. Our data suggest a specific role of AG in the regulation of
      gluconeogenesis to maintain euglycemia during pregnancy when energy availability
      is limited.

PMID- 27701683
TI  - Crocus sativus L. versus Citalopram in the Treatment of Major Depressive Disorder
      with Anxious Distress: A Double-Blind, Controlled Clinical Trial.
AB  - Introduction: Saffron (Crocus sativus L.) has demonstrated antidepressant effects
      in clinical studies and extensive anxiolytic effects in experimental animal
      models. Methods: 66 patients with major depressive disorder accompanied by
      anxious distress were randomly assigned to receive either saffron (30 mg/day) or
      citalopram (40 mg/day) for 6 weeks. Hamilton Rating Scale for Depression (HAM-D)
      and Hamilton Rating Scale for Anxiety (HAM-A) were used to assess treatment
      effect during the trial. Results: 60 participants finished the study. Patients
      who received either saffron or citalopram showed significant improvement in
      scores of the Hamilton Rating Scale for Depression (P-value<0.001 in both groups)
      and Hamilton Rating Scale for Anxiety (P-value<0.001 in both groups). Comparison
      of score changes between the 2 trial arms showed no significant difference (P
      value=0.984). Frequency of side effects was not significantly different between
      the 2 groups. Discussion: The present study indicates saffron as a potential
      efficacious and tolerable treatment for major depressive disorder with anxious
      distress.

PMID- 27701684
TI  - [Science based medicine].

PMID- 27701685
TI  - [Testing for thrombophilia in patients with venous thromboembolism - why and whom
      to test?]
AB  - Hereditary and acquired thrombophilias are known risk factors for a first venous
      thromboembolism (VTE). In contrast, the relative risk of VTE recurrence in
      presence of hereditary thrombophilia seems to be at most moderately elevated.
      However, thrombophilia still contributes to a greater extent to the absolute risk
      of VTE recurrence. This is explained by the 20-50-fold increased risk of VTE in a
      subject after a first VTE when compared to the state without previous VTE.
      Testing for thrombophilia may therefore be helpful in patients at intermediate
      risk of recurrence in whom the finding of a "strong" thrombophilia can bring
      about a decision for long-term anticoagulation.

PMID- 27701686
TI  - [Adipositas - new aspects in internistic care before and after bariatric
      surgery].
AB  - Indication for bariatric or metabolic surgery depends primarily on body mass
      index. Recent study results however suggest, that other markers are more reliable
      predictors of metabolic success. A revision of indication criteria is therefore
      necessary especially for surgical therapy of type 2 diabetes mellitus.
      Postoperative management should include screening for postbariatric hypoglycemia
      and bone density. Furthermore psychologic surveillance is recommended.

PMID- 27701687
TI  - [Gait and balance disturbances of common age-associated neurologic diseases].
AB  - Gait and balance disturbances are age-related and lead to injuries, reduced
      mobility and loss of independence. This overview discusses established and new
      clinical features and pathophysiological aspects of common age-related
      neurological gait and balance disorders.

PMID- 27701689
TI  - [Influenza: Whats new?]
AB  - The burden of disease of influenza in Germany has been dominated by high rates of
      complications in elderly patients in years with high circulation of H3N2 viruses
      after the introduction of the new H1N1 strain in 2009. Human infections with
      avian influenza viruses occur mostly in China. Due to the potential of
      reassortment with human strains these cases are monitored closely. The efficacy
      of neuraminidase inhibitors (NI) has been newly rated. In randomized studies
      effects on reduction of complications could not be found, although large cohort
      studies have demonstrated a reduction of mortality in patients treated with vs.
      without neuraminidase inhibitors.The administration and acceptance of influenza
      vaccine is low in Germany in general and in risk populations. New vaccines have
      been introduced with quadrivalent vaccines covering both circulating B-types
      simultaneously and high dose vaccines for elder patients.

PMID- 27701688
TI  - [Direct oral anticoagulants (DOAC) in tumor patients].
AB  - There is only limited data for the use of direct oral anticoagulants (DOACs) in
      tumor patients and no data from prospective randomised trials comparing DOACs to
      the current standard care: low molecular weight heparine (LMWH). Therefore, DOACs
      must be used with caution and should be restricted to tumor patients with (1)
      contraindications for LMWH (e.g. HIT II, phobia of syringe) or (2) to the
      situations of prolonged anticoagulation after initial therapy with LMWH. Cancer
      associated disorders as well as side effects of chemotherapy as nausea and emesis
      have to be considered as well as potential substance-specific interactions. Data
      of future clinical trials in prophylaxis and treatment of venous thrombembolism
      in tumor patients will help to define the role of DOACs in this special patient
      cohort.

PMID- 27701690
TI  - [Sepsis: new findings and developments. Update 2016].
AB  - The incidence of sepsis increases in Germany from latest DRG evaluations and also
      the mortality is still at a high level. The aim of the new Sepsis - 3 definition
      is to optimize the identification and initiation of therapy. The treatment
      algorithms by Rivers (EGDT) are getting old. Rapid identification of septic
      patients, rapid administration of antibiotics and rapid therapy management are
      crucial.

PMID- 27701691
TI  - [Update on pericardial diseases].
AB  - In 2015, an updated version of the ESC guidelines on pericardial diseases was
      published. The new guidelines summarize findings in the area of etiology,
      diagnosis and therapy of pericardial diseases and introduce an algorithm to
      diagnose pericarditis. Additionally, criteria for hospital submission were
      introduced. The use of multimodal imaging procedures was emphasized and medical
      as well as interventional therapy strategies were adapted to current knowledge.

PMID- 27701693
TI  - [Evidence-based physical therapy of rheumatic diseases].
AB  - New studies increase the evidence, that different applications of physical
      therapy are effective. In patients with rheumatoid arthritis (RA) physiotherapy
      of the hands improve strength, joint mobility and activity without increased risk
      of pain nor inflammation. A theory-based physiotherapy of the hands shows
      clinical effectiveness and cost-utility. In patients with spondyloarthritides
      supervised group exercise training is more effective than home exercise programs.
      Compared with biologics only combined exercise training and tumour necrosis
      factor alpha inhibitor therapy improve mobility and disease activity more
      effectively. Aerobic exercise training reduces fatigue in RA. Working wrist
      splints and static resting splints improve pain and grip strength. Static resting
      splints reduce the risk of hand deformities. Local and whole body cryotherapy
      show short term improvement of pain and inflammatory activity. German S3
      guidelines recommend enhanced utilisation of physical therapy as well as
      coordinated multiprofessional team care and rehabilitation.

PMID- 27701692
TI  - [Alpha-1-antitrypsin deficiency - an update].
AB  - Alpha-1-antitrypsin deficiency is a genetic risk factor for the development of
      chronic obstructive airway disease (COPD) and liver cirrhosis. The disease is
      widely underdiagnosed. The hallmarks of therapy are smoking cessation, prevention
      from environmental dust exposure and augmentation therapy. Findings from the
      recently published prospective, placebo-controlled and randomized RAPID trial
      proved effectiveness of AAT augmentation therapy for slowing progression of
      emphysema, measured by CT lung density. CT lung density may be more sensitive
      than forced exspiratory volume in one second (FEV1) or monoxid diffusion capacity
      (DLCO). The data suggest that higher therapeutic serum AAT levels lead to lower
      decline in lung density.

PMID- 27701694
TI  - [Celiac disease].
AB  - Celiac disease occurs as a result of a T-cell-dependent immune reaction on gluten
      peptides. It is a complex genetic disorder that is mediated by an unknown number
      of genes, of which more than 50 have been identified in whole genome association
      studies. The genetic component helps identify oligosymptomatic or even
      subclinical celiacs by screening first-degree relatives and patients suffering
      from other autoimmune diseases. To offer sensitive as well as specific
      diagnostics for celiac disease (serology and small intestinal histology) some
      general rules should be followed including performing diagnostics only when
      patients are on a gluten-containing diet or after an appropriate re-exposition.
      Established treatment is currently restricted to a gluten-free diet. However,
      future treatment options might include endopeptidase-mediated inactivation of
      gluten peptides, stabilization of the epithelial barrier, tissue-transglutaminase
      inhibition or vaccination.

PMID- 27701695
TI  - [67-year old woman with long-standing microcytic anemia].

PMID- 27701696
TI  - [Severe hypoglycemia following tramadol intake in a 79 year old non-diabetic
      patient].
AB  - History and clinical findings | We report about a 79 year old non-diabetic
      patient who was admitted to the emergency room with severe hypoglycemia (blood
      glucose level: 36 mg / dl and Glasgow Coma Scale Score: 3). After the infusion of
      G40 % her blood glucose level stabilised. The patient reported to have taken 50
      mg of Tramadol during the night to treat her headache. Investigations and
      diagnosis | No other differential diagnosis for hypoglycemia (i.e. diabetes,
      insulinoma, severe liver or kidney disease) could be established. Therefore, we
      suspected a tramadol induced hypoglycemia. The mechanisms and the risk factors
      for this potential side effect remain unclear. The patient showed no abnormality
      in metabolism (CYP2D6) or membrane transport (OCT1) of tramadol. Treatment and
      course | No further treatment for hypoglycemic episodes was needed. The patient
      was discharged after the differential diagnosis and pharmacogenetic testing was
      completed. Conclusions | Hypoglycemia is a little known adverse effect after
      tramadol intake, which has only been published in few cases. Tramadol, a weak
      opioid analgesic classified as step 2 of the WHO cancer pain ladder, is used in
      moderate pain. Given the continuous rise in tramadol prescription due to better
      management of chronic pain, further investigation of this issue seems needed as
      well as an increased awareness amongst physicians.

PMID- 27701697
TI  - [End-of-life Decisions].
AB  - End-of-life decisions in neurology have repeatedly given occasion for
      controversies. Often these are based on lack of knowledge of the juridical and
      ethical framework conditions. This review describes the juridical-ethical basis
      for the implementation and continuation, and for withholding and withdrawal of
      life-sustaining measures, in particular, the significance of medical indication
      and patient's will. The different forms of assisted dying ("Sterbehilfe"), namely
      homicide by request, assisted suicide, palliative symptom relief and treatment
      withdrawal are characterized. The "Principles of the German Medical Association"
      in end-of-life situations are illustrated. Specific features of neurological
      treatment scenarios are discussed such as the preclinical and clinical emergency
      and acute situation, the decompensation of stable chronic severe brain injury
      situations, and chronically progressive neurodegenerative diseases. In the latter
      situations, an early "Advance Care Planning" could contribute to improved end-of
      life decision-making.

PMID- 27701698
TI  - Forecasting the Future: Challenges and Opportunities in Developmental
      Communication Disorders.

PMID- 27701699
TI  - Autism Spectrum Disorder: From Pensieve to Crystal Ball.
AB  - In the next decade, professionals in communication sciences and disorders will
      encounter a wealth of needs, opportunities, and challenges in research and
      practice related to autism spectrum disorder. What lies ahead will reflect both
      transformations of and continuities with past perspectives (psychodynamic,
      biological, and learning theory). Among our largest challenges as individuals and
      as a discipline will be to determine the most important needs to address and the
      most productive opportunities to seize. Interprofessional collaboration,
      community engagement, and partnerships among researchers, practitioners, and
      community stakeholder are all strategies that can better guide our selection of
      priorities.

PMID- 27701700
TI  - Pursuing Precision Speech-Language Therapy Services for Children with Down
      Syndrome.
AB  - The behavioral phenotype of individuals with Down syndrome (DS) offers one avenue
      for developing speech-language therapy services that are tailored to the
      individual's characteristics that affect treatment response. Behavioral
      phenotypes are patterns of behavioral strengths and weaknesses for specific
      genetic disorders that can help guide the development and implementation of
      effective interventions. Nonetheless, individual differences within children with
      DS must be acknowledged and addressed because behavioral phenotypes are
      probabilistic, not deterministic. Developing precision speech-language therapy
      services to maximize learning opportunities and outcomes for children with DS
      calls for increased collaboration among clinicians and researchers to address the
      needs, challenges, and opportunities on three interconnected themes: (1) moving
      effective interventions from research to practice, (2) making evidence-based,
      child-specific treatment intensity decisions, and (3) considering child
      motivation and temperament characteristics. Increased availability of
      intervention materials and resources as well as more specific recommendations
      that acknowledge individual differences could help narrow the research-practice
      gap. Clear descriptions of disciplined manipulations of treatment intensity
      components could lead to more effective intervention services. Last, addressing
      motivation and temperament characteristics, such as the personality-motivation
      orientation, in children with DS may help maximize learning opportunities.
      Focused attention and collaboration on these key themes could produce
      substantial, positive changes for children with DS and their families in the
      coming decade.

PMID- 27701701
TI  - A Look into the Crystal Ball for Children Who Are Deaf or Hard of Hearing: Needs,
      Opportunities, and Challenges.
AB  - Hearing is essential for the development of speech, spoken language, and
      listening skills. Children previously went undiagnosed with hearing loss until
      they were 2.5 or 3 years of age. The auditory deprivation during this critical
      period of development significantly impacted long-term listening and spoken
      language outcomes. Due to the advent of universal newborn hearing screening, the
      average age of diagnosis has dropped to the first few months of life, which sets
      the stage for outcomes that include children with speech, spoken language, and
      auditory skill testing in the normal range. However, our work is not finished.
      The future holds even greater possibilities for children with hearing loss.

PMID- 27701702
TI  - Playing the Long Game: Considering the Future of Augmentative and Alternative
      Communication Research and Service.
AB  - This article examines the growth of aided augmentative and alternative
      communication (AAC) in providing support to children and youth with significant
      communication needs. Addressing current trends and offering a discussion of needs
      and probable future advances is framed around five guiding principles initially
      introduced by Williams, Krezman, and McNaughton. These include: (1) communication
      is a basic right and the use of AAC, especially at a young age, can help
      individuals realize their communicative potential; (2) AAC, like traditional
      communication, requires it to be fluid with the ability to adapt to different
      environments and needs; (3) AAC must be individualized and appropriate for each
      user; (4) AAC must support full participation in society across all ages and
      interests; and (5) individuals who use AAC have the right to be involved in all
      aspects of research, development, and intervention. In each of these areas
      current advances, needs, and future predictions are offered and discussed in
      terms of researchers' and practitioners' efforts to a continued upward trajectory
      of research and translational service delivery.

PMID- 27701703
TI  - Language Disorders in Adolescents: Current Needs and Future Directions.
AB  - Adolescents with developmental language disorders often do not receive the type
      of intervention that would improve their ability to speak, listen, read, and
      write effectively. Part of the problem is that many of these young people show no
      obvious symptoms of a language disorder, yet they struggle on a daily basis to
      succeed at school-related tasks that require a sophisticated level of language
      development. This article discusses some of the challenges these students face
      and makes suggestions for what could be done to address the issues. These
      suggestions include continuing the effort to advocate strongly for the rights of
      adolescents, increasing collaboration between speech-language pathologists and
      other professionals in the schools, and making changes to training programs in
      communication sciences and disorders to better prepare future speech-language
      pathologists to work with adolescents.

PMID- 27701705
TI  - Childhood Stuttering: Where Are We and Where Are We Going?
AB  - Remarkable progress has been made over the past two decades in expanding our
      understanding of the behavioral, peripheral physiologic, and central
      neurophysiologic bases of stuttering in early childhood. It is clear that
      stuttering is a neurodevelopmental disorder characterized by atypical development
      of speech motor planning and execution networks. The speech motor system must
      interact in complex ways with neural systems mediating language and other
      cognitive and emotional processes. During the time when stuttering typically
      appears and follows its path to either recovery or persistence, all of these
      neurobehavioral systems are undergoing rapid and dramatic developmental changes.
      We summarize our current understanding of the various developmental trajectories
      relevant for the understanding of stuttering in early childhood. We also present
      theoretical and experimental approaches that we believe will be optimal for even
      more rapid progress toward developing better and more targeted treatment for
      stuttering in the preschool children who are more likely to persist in
      stuttering.

PMID- 27701704
TI  - Nexus to Lexis: Phonological Disorders in Children.
AB  - Research on phonological disorders in children has conventionally emphasized the
      speech sound in search of causes, diagnoses, treatments, and prevention of the
      disorder. This article aims to shift the research focus to the word instead. The
      motivation comes from advances in psycholinguistics that demonstrate the word is
      central to the perception, production, and acquisition of phonological
      information. Three strands of potential study are outlined in evaluation of how
      words might initiate and boost, but perhaps also, interrupt learning for children
      with phonological disorders.

PMID- 27701706
TI  - Pediatric Feeding/Swallowing: Yesterday, Today, and Tomorrow.
AB  - Speech-language pathologists (SLPs) have played primary roles in the evaluation
      and management of children with feeding/swallowing disorders for more than five
      decades. Medical, surgical, and technological advances have improved the survival
      of young fragile infants and children, many of whom will present with
      feeding/swallowing problems. Regardless of their underlying etiologies, many of
      these children are at risk for aspiration-induced lung disease, undernutrition or
      malnutrition, developmental deficits, and stressful interactions with their
      caregivers. Unfortunately, our understanding of the physiology/pathophysiology of
      swallowing and its maturation, the development of standardized and efficacious
      evaluation and therapy tools, and identification of functional outcomes have not
      kept pace with our ability to identify children who are at increased risk for
      dysphagia and the associated sequelae. Given this paucity of evidence to guide
      practice in pediatrics, clinicians rely upon a combination of data extrapolated
      from adults with dysphagia, anecdotal reports, and institution-specific
      guidelines. This article focuses on updates in population demographics and
      advances in evaluation and treatment over the past decade and identifies future
      directions that may enable us to meet the needs of the children who are in our
      care to attain functional outcomes.

PMID- 27701707
TI  - Children with Specific Language Impairment and Their Families: A Future View of
      Nature Plus Nurture and New Technologies for Comprehensive Language Intervention
      Strategies.
AB  - Future perspectives on children with language impairments are framed from what is
      known about children with specific language impairment (SLI). A summary of the
      current state of services is followed by discussion of how these children can be
      overlooked and misunderstood and consideration of why it is so hard for some
      children to acquire language when it is effortless for most children. Genetic
      influences are highlighted, with the suggestion that nature plus nurture should
      be considered in present as well as future intervention approaches. A nurture
      perspective highlights the family context of the likelihood of SLI for some of
      the children. Future models of the causal pathways may provide more specific
      information to guide gene-treatment decisions, in ways parallel to current
      personalized medicine approaches. Future treatment options can build on the
      potential of electronic technologies and social media to provide personalized
      treatment methods available at a time and place convenient for the person to use
      as often as desired. The speech-language pathologist could oversee a wide range
      of treatment options and monitor evidence provided electronically to evaluate
      progress and plan future treatment steps. Most importantly, future methods can
      provide lifelong language acquisition activities that maintain the privacy and
      dignity of persons with language impairment, and in so doing will in turn enhance
      the effectiveness of speech-language pathologists.

PMID- 27701708
TI  - Professor Gerhard Lausberg.

PMID- 27701709
TI  - After EMPA-REG OUTCOME and LEADER: Already a "New Era" in Therapy of Type 2
      Diabetes?
AB  - Critical discussion of the cardiovascular findings with empagliflozin (EMPA-REG
      OUTCOME Study)and liraglutide (LEADER Study) and the consequences.

PMID- 27701710
TI  - Commentary on "Effects of Long-Term Exercise Interventions on Glycaemic Control
      in Type 1 and Type 2 Diabetes: A Systematic Review".

PMID- 27701711
TI  - Filling the Gap - Improving Awareness and Practice in Hyponatraemia and the
      Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in the Older
      Patient: A European Consensus View.
AB  - Introduction: Causes of hyponatraemia in older patients are multivariate and in
      the case of SIADH may often be drug induced. Diagnostic and treatment algorithms
      are unclear for this important age group. Methods: The author group identified 6
      broad themes for consensus and formulated 42 separate consensus statements within
      these 6 themes. Statements were then circulated to geriatricians, general
      practitioners and other doctors to test agreement at the European level. Results:
      64 responses were evaluated from around Europe. Agreement was achieved in 86% of
      the statements following amendment and redistribution of 6 of the statements. The
      survey and its feedback prompted the development of 13 recommendations related to
      the diagnosis and treatment of hyponatraemia including SIADH. Conclusion: The
      series of 13 recommendations developed here is intended to increase clarity for
      clinicians managing older patients with hyponatraemia and SIADH. Surprisingly,
      despite the lack of clear guidelines or recommendations for this age group
      consensus levels for the author-based statements were high among the respondents.

PMID- 27701712
TI  - Downregulation of Notch Signaling Pathway as an Effective Chemosensitizer for
      Cancer Treatment.
AB  - Despite remarkable progress in cancer treatment, development of drug resistance
      is still a big burden to eliminate all tumor cells and a mean cause for tumor
      recurrence. Recent studies have been revealed the contribution of many signaling
      pathways in acquisition of resistance to chemotherapy. Because of its potential
      in maintaining the balance between cell proliferation and apoptosis, Notch
      signaling pathway has mean relevance to various aspects of cancer biology, from
      cancer stem cells to tumor immunity to multidrug resistance. Therefore, Notch
      signaling pathway is an attractive target for cancer therapy because targeting
      Notch signaling could overcome multi drug resistance (MDR). This article will
      provide a brief overview of the published evidences in support of Notch targeting
      in reverting multidrug resistance as a safer and novel approach for the
      improvement of tumor treatment.

PMID- 27701713
TI  - An Update on Biomedical Application of Nanotechnology for Alzheimer's Disease
      Diagnosis and Therapy.
AB  - Approximately 35 million people worldwide suffer from Alzheimer's disease (AD).
      The cellular uptake and specific transport of drugs and imaging agents to brain
      are common issues in the diagnosis and therapy of AD. New advances in
      nanotechnology have supplied favorable solutions to this issue. Various
      nanocarriers such as polymeric nanoparticles, liposomes, micelles, dendrimers and
      nanogels have been studied for the delivery of drugs and imaging agents to brain.
      This review presents a succinct discussion of the applications of nanotechnology
      for Alzheimer's disease diagnosis and therapy.

PMID- 27701714
TI  - The Therapeutic Effect of Pancreatic Kininogenase on Treatment of Diabetic
      Peripheral Neuropathy in Patients with Type 2 Diabetes.
AB  - Background: To determine the therapeutic efficacy and cost-effective of
      pancreatic kininogenase (PKase) on treatment of diabetic peripheral neuropathy
      (DPN) compared with Prostaglandin E1 (PGE1) in patients with type 2 diabetes.
      Methods: 104 patients with DPN receiving standard glucose control therapy were
      randomly assigned into 3 groups: Group-A received PKase treatment, Group-B
      received PGE1 treatment, and Group-C received only standard glucose control
      therapy. Michigan neuropathy screening instrument (MNSI) score, neurophysiology
      examination, and nerve conduction velocity were measured. Results: Standard
      glucose control therapy significantly reduced hyperglycemia to a similar level in
      all groups. Questionnaire grading and neurophysiology examination both indicated
      that no significant difference was found at the end of treatment between Groups 
      A and -B. Except for the ulnar nerve sensory conduction velocity that was
      significantly improved in Group-B, the remaining nerve conduction velocity
      (regardless of sensory or motor nerve conduction velocities) was improved to a
      similar level in Groups -A and -B. Group-A had significantly reduced
      questionnaire grading and better improvement in motor nerve conduction velocity
      of the common peroneal nerve, ulnar nerve, and sensory nerve conduction velocity
      of the sural nerve as compared with Group-C. However, the medical cost of PKase
      was only 18.9% of that of PGE1 during one course of treatment. Conclusions: PKase
      has the similar therapeutic efficacy as PGE1 on treatment of DPN in patients with
      type 2 diabetes. However, the medical cost of PKase is one fifth of that of PGE1.
      Thus, PKase is a cost-effective drug for treatment of DPN.

PMID- 27701715
TI  - Hypothyroidism Induces a Moderate Steatohepatitis Accompanied by Liver
      Regeneration, Mast Cells Infiltration, and Changes in the Expression of the
      Farnesoid X Receptor.
AB  - Hypothyroidism is associated with the development of non-alcoholic
      steatohepatitis, but cellular mechanisms have been scarcely analyzed. Thyroid
      hormones regulate the synthesis and secretion of bile acids that are endogenous
      ligands of the farnesoid receptor (FXRalpha), which have been involved in the
      development of non-alcoholic steatohepatitis. However, the relationship between
      thyroid hormones and FXRalpha expression in the liver is yet unknown. Control
      (n=6) and methimazole-induced hypothyroid (n=6) female rabbits were used to
      evaluate the amount of lipids and glycogen, vascularization, hepatocytes
      proliferation, immune cells infiltration, and expression of FXRalpha. Student-t
      or Mann-Whitney U tests were carried out to determine significant differences.
      Hypothyroidism induced steatosis, glycogen loss, fibrosis, and a minor
      vascularization in the liver. In contrast, hypothyroidism increased the
      proliferation of hepatocytes and the infiltration of mast cells, but did not
      modify the number of immune cells into sinusoids. These changes were associated
      with a minor anti-FXRalpha immunoreactivity of periportal hepatocytes and
      pericentral immune cells. Our results suggest that hypothyroidism induces a
      moderate non-alcoholic steatohepatitis, alllowing the hepatic regeneration. The
      FXRalpha may be involved in the development of non-alcoholic steatohepatitis in
      hypothyroid subjects.

PMID- 27701716
TI  - The Influence of Type 1 Diabetes Mellitus on Pulmonary Function and Exercise
      Capacity - Results from the Study of Health in Pomerania (SHIP).
AB  - Background: Diabetes mellitus Type 1 (T1DM) is associated with metabolic and
      microvascular diseases as part of a multi-organ and multi-systemic disorder. The
      dense network of capillary vessels in the lungs may change during the course of
      the development of microangiopathy. The connective tissue as well as alveoli may
      be subjected to non-enzymatic glycosylation of proteins which may in turn affect
      pulmonary function. Previous studies investigating lung function in patients with
      type 1 diabetes have only been performed on small numbers of patients. Our study
      is based on population data of the Study of Health in Pomerania (SHIP).
      Objective: To investigate the influence of metabolic control on pulmonary system
      function and to establish a decreased pulmonary system function as a late
      complication of T1DM in a population based setting. Methods: The study is a case
      matched study with multiple controls based on participants with T1DM (SHIP-DM-1,
      n=73) and non-diabetics (SHIP-1, n=292) from the population based study of
      Pomerania. Data on lung function and exercise performance stratified by age, sex,
      body mass index and smoking habits in participants with T1DM and without diabetes
      were matched. Results: Participants with T1DM showed a significantly lower total
      lung capacity, residual volume and forced vital capacity. The transfer factor for
      carbon monoxide, the maximum power output and oxygen uptake during exercise were
      significantly decreased in comparison to the general population without diabetes.
      Conclusion: The pattern of abnormal pulmonary function as observed in the present
      study with a reduction in lung volume parameters and reduced oxygen uptake in
      participants with T1DM suggests a restrictive type of lung disease caused by an
      intrinsic lung tissue derangement as well as pulmonary microangiopathy.

PMID- 27701718
TI  - Evaluation of Nanocarrier Targeted Drug Delivery of Capecitabine-PAMAM Dendrimer
      Complex in a Mice Colorectal Cancer Model.
AB  - Capecitabine, an effective anticancer drug in colorectal cancer chemotherapy, may
      create adverse side effects on healthy tissues. In the present study, we first
      induced colon adenocarcinoma with azoxymethane, a carcinogen agent, and then
      investigated the potentiality of polyamidoamine (PAMAM) dendrimer to improve
      capecitabine therapeutic index and decrease its adverse side effects on healthy
      tissues like liver and bone marrow. Other variables such as nanoparticle
      concentrations have also been investigated. Drug loading concentration (DLC) and
      encapsulation efficiency (EE) were calculated for capecitabine/dendrimer complex.
      Experimental results showed an increase in DLC percentage resulted from elevated
      capecitabine/dendrimer ratio. Capecitabine/dendrimer complex could reduce tumor
      size and adverse side effects in comparison with free capecitabine form.

PMID- 27701717
TI  - Protective Effect of 25Mg-Porphyrin-Fullerene Nanoparticles on Oxygen-Glucose
      Deprivation/Reperfusion Injury in PC12 Cells.
AB  - We investigated the effects of 25Mg-Porphyrin-Fullerene nanoparticles,
      (25MgPMC16) smart ferroporphyrin nanoparticles, on PC12 cells exposed to oxygen
      glucose deprivation/reperfusion. In order to explore its effect on cells under
      oxygen-glucose deprivation conditions, the cultures were pretreated with
      25MgPMC16 24 hours prior to oxygen-glucose deprivation/reperfusion. To initiate
      the oxygen-glucose deprivation/reperfusion, the cell culture medium was replaced
      with a glucose-free medium and the cells were transferred to a humidified
      incubation chamber in a mixture of 95% N2 and 5% CO2 at 37 degrees  C for 30, 60
      and 120 min. Cell viability was assessed by MTT assay. Exposure of PC12 cells to
      30, 60 and 120 min oxygen-glucose deprivation significantly decreased the cell
      viability. Pretreatment of the cultures with 25MgPMC16 significantly increased
      cell viability in a concentration-dependent manner. Pretreatment, the cultures
      with MK-801 (10 uM), a non-competitive NMDA antagonist, has attenuated the cell
      death after 30 min oxygen-glucose deprivation. We concluded that 25MgPMC16 could
      protect PC12 cells against oxygen-glucose deprivation/reperfusion-induced cell
      injury in a concentration-dependent manner. That could be due to the effect of
      25MgPMC16 on ATP synthesis and the antioxidant effects of its components.

PMID- 27701719
TI  - Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson's Disease.
AB  - Antioxidants have protective effects against free radicals-induced neural damage
      in Parkinson's disease (PD). We examined the effects of ellagic acid (EA) on
      locomotion, pallidal local EEG, and its frequency bands' power and also cerebral
      antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA).
      6-OHDA (16 ug/2u l) was injected into the right medial forebrain bundle (MFB) in
      MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model
      was confirmed by rotational test using apomorphine injection. EA (50 mg/kg/2 ml,
      by gavages) was administered in PD+EA group. One group of MFB-lesioned rats
      received pramipexole (PPX; 2 mg/kg/2 ml, by gavages) as a positive control group
      (PD+PPX group). Motor activity was assessed by stride length, rotarod, and
      cylinder tests. Pallidal local EEG was recorded in freely moving rats. The levels
      of malondialdehyde (MDA) besides Glutathione peroxidase (GPx) and superoxide
      dismutase (SOD) activities were measured in both striatum and hippocampus
      tissues. MFB lesion caused significant reduction of stride-length (P<0.001), bar
      decent latency (P<0.001) and frequency bands' power of pallidal EEG (P<0.001).
      Use of 6-OHDA caused a reduction in the GPx (P<0.001) and SOD (P<0.001)
      activities while increased significantly the levels of MDA (P<0.001) in MFB
      lesioned rats. EA significantly restored all above parameters. The results show
      that EA can improve the motor impairments and electrophysiological performance in
      the MFB-lesioned rats via raising the cerebral antioxidant contents. Therefore,
      EA can protect the brain against free radicals-induced neural damage and may be
      beneficial in the treatment of PD.

PMID- 27701720
TI  - A Comparison of Effectiveness of Parent Behavioral Management Training and
      Methylphenidate on Reduction of Symptomsof Attention Deficit Hyperactivity
      Disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most common
      psychological disorders of childhood. Methylphenidate is highly effective in the
      treatment of ADHD. This study aimed to determine the effectiveness of combined
      Parent behavioral management training (PBMT) and medication treatment
      (Methylphenidate) in reducing ADHD symptoms in 6-12-year-old children, using
      randomized sampling. A total of 50 children with ADHD were assigned into two
      groups: an experimental group of PBMT and a control group of medication treatment
      (Methylphenidate) without other interventions. Conners' Parent Rating Scale (CPRS
      48) was employed before and after interventions to determine the effects.
      Descriptive Statistics method (consisting of Mean and Standard deviation) and
      Statistical inference method, (including t-test and Levene's Test) were used for
      data analysis.  Findings revealed that the combined behavioral intervention of
      PBMT and methylphenidate treatment is more effective in reduction of ADHD in
      children. The difference of means between pre-test and post-test of CPRS in the
      experimental group was equal to 10.77, and it was equal to 1.88 in the control
      group. In addition, PBMT was more effective in the case of younger parents
      (P<0.025). However, parents' education level did not affect the behavioral
      intervention (P<0.025).The findings suggest that combined intervention of PBMT
      and methylphenidate is effective in reducing the symptoms of ADHD in children.

PMID- 27701721
TI  - Deficiency in Mental Rotation of Upper and Lower-Limbs in Patients With Multiple
      Sclerosis and Its Relation With Cognitive Functions.
AB  - Mental rotation is a cognitive motor process which was impaired in different
      neurologic disorders. We investigated whether there were deficits in response
      pattern, reaction time and response accuracy rate of mental rotation in multiple
      sclerosis (MS) patients compared to healthy subjects and whether cognitive
      dysfunctions in MS patients were correlated with mental rotation deficits.
      Moreover, we showed whether there was a difference between upper and lower-limbs
      mental rotation in MS patients. Thirty-five MS patients and 25 healthy subjects
      performed hand mental rotation (HMR) and foot mental rotation (FMR) tasks. Visual
      information processing speed, spatial learning and memory ability, and
      visuospatial processing were assessed by Symbol Digit Modalities Test (SDMT),
      Brief Visuospatial Memory Test-Revised (BVMT-R), and Judgment of Line Orientation
      Test (JLO) respectively in MS patients. Reaction time for both hand and foot
      stimuli increased, and response accuracy rate for hand stimuli decreased in MS
      patients compared to healthy subjects, but response pattern of mental rotation in
      MS patients persisted. Similar to healthy subjects, MS patients performed upper
      limbs mental rotation more easily than a lower-limbs mental rotation with more
      speed and response accuracy rate. Reaction time and response accuracy rate were
      correlated with the mentioned cognitive functions. MS patients made use of the
      correct response pattern for problem solving of increasing orientation from
      upright stimuli. Reaction time and response accuracy rate altered in these
      patients and this alteration might occur along with impairment in motor planning.
      Subjects' better responding to hand stimuli was due to more familiarity with hand
      stimuli. The correlation of mental rotation ability with cognitive functions
      indicates the possible role of cognitive functions in mental rotation.

PMID- 27701722
TI  - Cross-Cultural Adaptation, Reliability and Validity Study of the Persian Version
      of the Clinical COPD Questionnaire.
AB  - The clinical COPD questionnaire (CCQ) has been developed to measure the health
      status of COPD patients. The aim of this study was to translate CCQ into the
      Persian language and assess the validity and reliability of the translated
      version. We used a forward-backward procedure to translate the questionnaire. In
      a cross-sectional study 100 COPD patients and 50 healthy subjects over 40 years
      old were selected to assess the reliability and construct validity of the
      instrument. The face and content validity were used for the questionnaire
      validity. Validity was examined in a population of patients with COPD, using the
      Persian validated version of the St George's Respiratory Questionnaire (PSGRQ).
      In order to assess the questionnaire's reliability, the Intraclass correlation
      coefficient (ICC) and Cronbach's alpha were calculated. Test-retest reliability
      was tested by re-administering the Persian version of the CCQ (PCCQ) after 1
      week. Test-retest carry out of data demonstrates that the PCCQ has excellent
      reliability (ICC for all 3 domains were higher than 0.9). Internal consistency
      was found by Cronbach's alpha to be 0.96, 0.94, 0.97, and 0.98 for the symptom,
      mental state, functional state and total scores respectively. In addition, the
      correlation between the components of PCCQ and PSGRQ showed satisfactory
      construct validity. Analyzing the data from healthy subjects and patients
      divulged that the PCCQ has acceptable discriminant validity. In general, the PCCQ
      had satisfactory reliability and validity for assessing health-related quality of
      life status of Iranian COPD patients.

PMID- 27701723
TI  - Annual Report of Drug and Poison Information in Iran From March 2012 to March
      2013.
AB  - Drug and Poison Information Centers (DPICs) have a critical role in the
      fulfillment of rational drug use programs and provide services to the scientific
      community with the aim of improving the health and safety of drug use. This was a
      retrospective study on recorded calls of DPICs in Iran from March 2012 to March
      2013. Data consisted of general information; drug and poisoning information,
      medical history and also the distribution of a number of calls collected by DPICs
      in Iran. The centers received a total of 171769 calls. Most calls were made by
      the patients (56.1%) and then the patients' relatives (38%). Also, 67% of the
      patients were determined as female. The calls mostly were focused on Adverse Drug
      Reactions (ADR) (15.3%), indications (14.0%) and drug evaluations (11.8%). Anti
      infective agents, non-steroidal anti-inflammatory drugs (NSAIDs) and vitamins
      with 9.6%, 7%, and 6.8% frequencies were the highest frequently asked questions,
      respectively. Based on the results, patients do not receive enough information
      about their medications, from physicians and pharmacists. The DPICs have an
      important role to guide the people and provide the accurate drug and poison
      information and fill the absence of information that is not provided by medical
      staff. So, based on the important role of these centers, it is worth the Iran
      DPICs being introduced more to people, and we need more advertising around the
      country.

PMID- 27701724
TI  - Clinical Clerkship Education Improves With Implementing a System of Internal
      Program Evaluation Using Medical Students' Feedbacks.
AB  - Quality of clinical education for medical students has always been a concern in
      academic medicine. This concern has increased in today's time-squeeze while
      faculty members have to fulfill their complementary roles as a teacher,
      researcher, and practitioner. One of the strategies for program evaluation is
      obtaining trainees' feedbacks since they are the main customers of educational
      programs; however, there are debates about the efficacy of student feedback as a
      reliable source for reforms. We gathered Likert scores on a 16-item questionnaire
      from 2,771 medical students participating in all clerkship programs in a
      multidisciplinary teaching hospital. An expert panel consisting of 8 attending
      physicians established content validity of the questionnaire while a high
      Cronbach's Alpha (0.93) proved its reliability. Summary reports of these
      feedbacks were presented to heads of departments, clerkship program directors,
      and hospital administrators, at the end of each semester. Analysis of variance
      was used for comparing hospital scores across different time periods and
      different departments. Significant changes (P<0.001) were observed in mean scores
      between different semesters (partial eta2=0.090), different departments (partial
      eta2=0.149) as well as the interaction term between departments and semesters
      (partial eta2=0.111). A significant improvement in mean clinical education score
      is noticeable after three semesters from the beginning of the survey. Periodic,
      systematic trainee's feedback to program directors can lead to an improved
      educational performance in teaching hospitals.

PMID- 27701725
TI  - Efficacy of E-Learning via the Website of Tehran University of Medical Sciences
      for Diagnosing Tooth Discolorations and Treatment Planning by Senior Dental
      Students.
AB  - The efficacy of methods like e-learning as a supplement to traditional face-to
      face instruction needs to be evaluated in dental courses. This study aimed to
      assess the efficacy of posting case presentations on one of the educational
      websites of  the virtual school of Tehran University of Medical Sciences called
      "SARMAD" to enhance the ability of senior dental students to diagnose tooth
      discolorations and offer treatment plans. This experimental study had a pre
      test/post-test control group design and was conducted on 63 senior dental
      students. After filling out the primary questionnaire and obtaining a written
      informed consent, students participated in a pre-test and were then randomly
      divided into two groups of intervention and control. Fifteen case presentations
      were posted on the university website (SARMAD) during 6 weeks and discussed.
      Then, students participated in a post-test. Students' perspectives and their
      satisfaction with the website were assessed by a questionnaire. For ethical
      purposes, the same program was also offered to the controls. The post-test score
      was significantly higher than the pre-test score in the intervention group
      (P<0.001); but in the control group, the post-test score was only slightly higher
      than the pre-test score (P=0.128). In the intervention group, 70% stated that
      they would suggest this method as an efficient educational modality; 93.3% stated
      that this method would be beneficial as a supplement to conventional education;
      16.7% ranked the SARMAD website excellent, 30% ranked it good, 33.3% acceptable,
      16.7% moderate and 3.3 poor. It appears that this instructional modality may be
      efficiently used as a supplement to traditional instruction in undergraduate
      dental curricula.

PMID- 27701726
TI  - Effect of Air Pollution in Frequency of Hospitalizations in Asthmatic Children.
AB  - Asthma is one of the most common diseases in childhood, which has been increased
      during last decade because of epidemiological pattern changes with climate and
      industrialization of the communities. There are some controversies on the
      relationship between air pollution and asthma. Tehran, as the capital of Iran, is
      one of the densest populations and is one of the most polluted cities in the
      world. This study was performed to search effects of various air pollutants using
      GIS-based modeling on the rate of hospitalizations due to asthma in children in
      Tehran. Information of patients who were admitted with a diagnosis of asthma in a
      referral pediatric hospital was checked and the total number of admissions in the
      same age range (2 to 14 years) during a 2-year period (March 2009-March 2011)
      were calculated. Information about air pollutants including carbon monoxide,
      nitrogen dioxide, ozone, and sulfur dioxide, obtained from the air quality
      control center. Days of the year divided into GOOD and NONGOOD days according to
      the guideline for reporting of the daily air quality index (AQI). Two thousand
      two hundred nineteen cases enrolled in the study and asthma admission to total
      admission ratio compared with air pollutants data in admission day (725 days),
      using nonlinear regression method. Analysis of the data revealed that there is a
      significant relationship between NONGOOD nitrogen dioxide (P=0.01), ozone
      (P=0.01), and sulfur dioxide (P=0.04), levels and admission due to asthma in
      children, but There was no significant relationship between carbon monoxide
      levels and asthma admission in children. A significant relationship between
      nitrogen dioxide, ozone and sulfur dioxide concentration in air and admission due
      to asthma at levels other than GOOD, reveals air pollutants levels can be
      significantly harmful to children before AQI reaches to hazardous levels.

PMID- 27701727
TI  - Unusual Ectopic Parathyroid Adenoma: A Case Report.
AB  - An ectopically placed parathyroid in the mediastinum is a rare cause of
      persistent or recurrent primary hyperparathyroidism. They are rarely in a huge
      size. We report a case of a 70-year-old man with a history of total
      parathyroidectomy and thymectomy presented with a lack of appetite, nausea, and
      generalized bone pain, polydipsia and a calcium level of 14.4 mg/dl. 99mTc
      sestamibi scintigraphy with single-photon emission computerized tomography
      (SPECT) showed a focal zone of radiotracer accumulation in the midline of
      anterior chest wall (xiphoid level). The mass excised from our patient surgically
      was 75 grams. This weight and location of the tumor is a very rare finding in
      parathyroid adenomas.

PMID- 27701728
TI  - Warfarin-Induced Skin Necrosis in Patients With Low Protein C Levels.
AB  - Warfarin-induced skin necrosis (WISN) is a rare complication of anticoagulant
      therapy associated with a high incidence of  morbidity and mortality requiring
      immediate drug cessation. At particular risk are those with various thrombophilic
      abnormalities, especially when warfarinisation is undertaken rapidly with large
      loading doses of warfarin. Cutaneous findings include petechiae that progress to
      ecchymosis and hemorrhagic bullae. With the increasing number of patients
      anticoagulated as out-patients for thromboprophylaxis, we are concerned that the
      incidence of skin necrosis may increase. We present a case of WISN with low
      protein C level. He was a 50-year-old male who came to our department because of
      acute infarction in irrigation area of the superior cerebellar artery. He had
      intermittent atrial fibrillation and was started on anticoagulant therapy.  After
      few day of therapy, he developed skin necrosis, and his level of protein C was
      low. Warfarin-induced skin necrosis is a rare but serious complication that can
      be prevented by routine screening for protein C, protein S or antithrombin
      deficiencies or for the presence of antiphospholipid antibodies before beginning
      warfarin therapy.

PMID- 27701729
TI  - Optimization of a beta-sheet-cap for long loop closure.
AB  - Protein loops make up a large portion of the secondary structure in nature. But
      very little is known concerning loop closure dynamics and the effects of loop
      composition on fold stability. We have designed a small system with stable beta
      sheet structures, including features that allow us to probe these questions.
      Using paired Trp residues that form aromatic clusters on folding, we are able to
      stabilize two beta-strands connected by varying loop lengths and composition (an
      example sequence: RWITVTI - loop - KKIRVWE). Using NMR and CD, both fold
      stability and folding dynamics can be investigated for these systems. With the 16
      residue loop peptide (sequence: RWITVTI-(GGGGKK)2 GGGG-KKIRVWE) remaining folded
      (DeltaGU  = 1.6 kJ/mol at 295K). To increase stability and extend the series to
      longer loops, we added an additional Trp/Trp pair in the loop flanking position.
      With this addition to the strands, the 16 residue loop (sequence: RWITVRIW
      (GGGGKK)2 GGGG-WKTIRVWE) supports a remarkably stable beta-sheet (DeltaGU  = 6.3
      kJ/mol at 295 K, Tm  = ~55 degrees C). Given the abundance of loops in binding
      motifs and between secondary structures, these constructs can be powerful tools
      for peptide chemists to study loop effects; with the Trp/Trp pair providing
      spectroscopic probes for assessing both stability and dynamics by NMR.

PMID- 27701730
TI  - Stercoral Ulcer and Colonic Perforation in an Individual with Parkinson's Disease
      with Constipation.

PMID- 27701731
TI  - Treating Trichotillomania (Hair-Pulling Disorder) in a Child.
AB  - Although cognitive behavioral treatments (CBTs) have been recommended as first
      line interventions for trichotillomania (hair-pulling disorder [HPD]), research
      on CBT for young children with HPD is limited. We illustrate the use of family
      based CBT for HPD in an 8-year-old boy. The client had a 5-year history of
      chronic HPD and several large bald spots on the crown of his head. Treatment
      primarily comprised habit reversal training (HRT) and function-based
      interventions. The child showed significant improvement in HPD severity and
      impairment after 8 weekly sessions, although complete abstinence was not
      achieved. The findings underscore the importance of parental involvement in the
      treatment and show that children as young as 8 years of age can successfully use
      strategies taught in HRT.

PMID- 27701732
TI  - Novel DNMT3A germline mutations are associated with inherited Tatton-Brown-Rahman
      syndrome.
AB  - Tatton-Brown-Rahman syndrome (TBRS) was recently described in 13 isolated cases
      with de novo mutations in the DNMT3A gene. This autosomal dominant condition is
      characterized by tall stature, intellectual disability and a distinctive facial
      appearance. Here, we report six cases of inherited TBRS caused by novel DNMT3A
      germline mutations. The affected individuals belong to two sib-ships: four from
      an Old Order Amish family in America and two from a French Canadian family in
      Canada. All of them presented with characteristic features of TBRS, including
      dysmorphic facial features, increased height, intellectual disability, and
      variable additional features. We performed clinical exome sequencing and
      identified two mutations in the DNMT3A gene, a c.2312G>A (p.Arg771Gln) missense
      mutation in the Amish family and a c.2296_2297delAA (p.Lys766Glufs*15) small
      deletion in the French Canadian family. Parental DNA analysis by Sanger
      sequencing revealed that the Amish mutation was inherited from the healthy mosaic
      father. This study reflects the first cases with inherited TBRS and expands the
      phenotypic spectrum of TBRS.

PMID- 27701733
TI  - Antigen presentation by B cells guides programing of memory CD4+ T-cell responses
      to a TLR4-agonist containing vaccine in mice.
AB  - The contribution of B cells to immunity against many infectious diseases is
      unquestionably important and well characterized. Here, we sought to determine the
      role of B cells in the induction of T-helper 1 (TH 1) CD4+ T cells upon
      vaccination with a tuberculosis (TB) antigen combined with a TLR4 agonist. We
      used B-cell deficient mice (MUMT-/- ), tetramer-positive CD4+ T cells, markers of
      memory "precursor" effector cells (MPECs), and T-cell adoptive transfers and
      demonstrated that the early antigen-specific cytokine-producing TH 1 responses
      are unaffected in the absence of B cells, however MPEC induction is strongly
      impaired resulting in a deficiency of the memory TH 1 response in MUMT-/- mice.
      We further show that antigen-presentation by B cells is necessary for their role
      in MPEC generation using B-cell adoptive transfers from wt or MHC class II knock
      out mice into MUMT-/- mice. Our study challenges the view that B-cell deficiency
      exclusively alters the TH 1 response at memory time-points. Collectively, our
      results provide new insights on the multifaceted roles of B cells that will have
      a high impact on vaccine development against several pathogens including those
      requiring TH 1 cell-mediated immunity.

PMID- 27701735
TI  - PINK1 in the limelight: multiple functions of an eclectic protein in human health
      and disease.
AB  - The gene PINK1 [phosphatase and tensin homologue (PTEN)-induced putative kinase
      1] encodes a serine/threonine kinase which was initially linked to the
      pathogenesis of a familial form of Parkinson's disease. Research on PINK1 has
      recently unravelled that its multiple functions extend well beyond
      neuroprotection, implicating this eclectic protein in a growing number of human
      pathologies, including cancer, diabetes, cardiopulmonary dysfunctions, and
      inflammation. Extensive studies have identified PINK1 as a crucial player in the
      mitochondrial quality control pathway, required to label damaged mitochondria and
      promote their elimination through an autophagic process (mitophagy). Mounting
      evidence now indicates that PINK1 activities are not restricted solely to
      mitophagy, and that different subcellular and even sub-mitochondrial pools of
      PINK1 are involved in distinct signalling cascades to regulate cell metabolism
      and survival. In this review, we provide a concise overview on the different
      functions of PINK1 and their potential role in human diseases. Copyright (c) 2016
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 27701734
TI  - Interleukin-33 regulates tissue remodelling and inhibits angiogenesis in the eye.
AB  - Age-related macular degeneration (AMD) is the leading cause of central vision
      loss worldwide. Loss of retinal pigment epithelium (RPE) is a major pathological
      hallmark in AMD with or without pathological neovascularization. Although
      activation of the immune system is implicated in disease progression,
      pathological pathways remain diverse and unclear. Here, we report an unexpected
      protective role of a pro-inflammatory cytokine, interleukin-33 (IL-33), in ocular
      angiogenesis. IL-33 and its receptor (ST2) are expressed constitutively in human
      and murine retina and choroid. When RPE was activated, IL-33 expression was
      markedly elevated in vitro. We found that IL-33 regulated tissue remodelling by
      attenuating wound-healing responses, including reduction in the migration of
      choroidal fibroblasts and retinal microvascular endothelial cells, and inhibition
      of collagen gel contraction. In vivo, local administration of recombinant IL-33
      inhibited murine choroidal neovascularization (CNV) formation, a surrogate of
      human neovascular AMD, and this effect was ST2-dependent. Collectively, these
      data demonstrate IL-33 as a potential immunotherapy and distinguishes pathways
      for subverting AMD pathology. (c) 2016 The Authors. The Journal of Pathology
      published by John Wiley & Sons Ltd on behalf of Pathological Society of Great
      Britain and Ireland.

PMID- 27701736
TI  - Molecular pathology of paediatric central nervous system tumours.
AB  - Advances in our understanding of the biology of paediatric central nervous system
      (CNS) tumours have encouraged pathologists to use molecular markers alongside
      histopathological analysis for disease classification or prognostication and
      treatment stratification. In this article, we review molecular genetic
      alterations in paediatric CNS tumours, including those in low-grade and high
      grade gliomas, ependymomas, and embryonal tumours. Some of these molecular
      changes with clinicopathological utility have been used for the first time in the
      most recent edition of the World Health Organization (WHO) classification of CNS
      tumours to define entities like ependymoma, RELA fusion-positive or diffuse
      midline glioma, H3 K27M-mutant. The classification of paediatric CNS tumours is
      entering a new era when histopathologists must work with molecular genetic data
      and their molecular pathology colleagues to provide an optimal diagnostic
      evaluation for their patients and clinical colleagues. Copyright (c) 2012
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 27701737
TI  - Isolation and functional characterization of CsLsi1, a silicon transporter gene
      in Cucumis sativus.
AB  - Cucumber (Cucumis sativus) is a widely grown cucurbitaceous vegetable that
      exhibits a relatively high capacity for silicon (Si) accumulation, but the
      molecular mechanism for silicon uptake remains to be clarified. Here we isolated
      and characterized CsLsi1, a gene encoding a silicon transporter in cucumber (cv.
      Mch-4). CsLsi1 shares 55.70 and 90.63% homology with the Lsi1s of a monocot and
      dicot, rice (Oryza sativa) and pumpkin (Cucurbita moschata), respectively. CsLsi1
      was predominantly expressed in the roots, and application of exogenous silicon
      suppressed its expression. Transient expression in cucumber protoplasts showed
      that CsLsi1 was localized in the plasma membrane. Heterologous expression in
      Xenopus laevis oocytes showed that CsLsi1 evidenced influx transport activity for
      silicon but not urea or glycerol. Expression of cucumber CsLsi1-mGFP under its
      own promoter showed that CsLsi1 was localized at the distal side of the
      endodermis and the cortical cells in the root tips as well as in the root hairs
      near the root tips. Heterologous expression of CsLsi1 in a rice mutant defective
      in silicon uptake and the over-expression of this gene in cucumber further
      confirmed the role of CsLsi1 in silicon uptake. Our results suggest that CsLsi1
      is a silicon influx transporter in cucumber. The cellular localization of CsLsi1
      in cucumber roots is different from that in other plants, implying the possible
      effect of transporter localization on silicon uptake capability.

PMID- 27701739
TI  - Assessment of ochratoxin A occurrence in Argentine red wines using a novel
      sensitive quechers-solid phase extraction approach prior to ultra high
      performance liquid chromatography-tandem mass spectrometry methodology.
AB  - BACKGROUND: The assessment of ochratoxin A (OTA) in wine is relevant for food
      safety and its continuous control allows to reduce the risk of intake. Thus, a
      novel sensitive QuEChERS-SPE (Quick, Easy, Cheap, Effective, Rugged and Safe -
      Solid Phase Extraction) pretreatment prior to liquid chromatography coupled to
      tandem mass spectrometry was developed for the determination of OTA in red wine
      samples from different grape-growing regions in Argentine. RESULTS: A sensitive
      methodology was achieved and thus the limits of detection and quantification were
      0.02 and 0.05 ug L-1 , respectively. Recoveries ranged from 89.0% to 105.3%. The
      method was applied to 136 red wine samples (Argentina's flagship varieties:
      Malbec and Cabernet Sauvignon) from ten grape-growing regions, during vintages
      2013-2015. Although all of the samples investigated were contaminated with OTA
      (concentrations ranged from 0.02 to 0.98 ug L-1 ), the levels detected were lower
      than the maximum allowable concentration limit of 2.0 ug L-1 established by
      international regulations. CONCLUSION: The methodology proposed is suitable for
      reliable OTA analysis in red wines. Similarly, the values obtained from the
      samples analyzed were in accordance with the current regulations and, as a
      consequence, preventive actions to reduce this mycotoxin incidence can be
      undertaken. (c) 2016 Society of Chemical Industry.

PMID- 27701738
TI  - Is the cause of sensorineural hearing loss in patients with facial schwannomas
      multifactorial?
AB  - OBJECTIVES: Facial nerve schwannomas (FNSs) and vestibular nerve schwannomas
      (VNSs) may occupy similar locations in the internal auditory canal (IAC). Risk
      factors for hearing loss in patients with FNS are unknown. Similar to VNSs, we
      hypothesize that the size and location of FNSs do not correlate with hearing
      loss. STUDY DESIGN: Retrospective cohort study and otopathology case review.
      METHODS: A single institution retrospective review of all patients diagnosed with
      FNS was performed. Demographic data, tumor size and location, severity and type
      of hearing loss, and facial nerve function were analyzed. Otopathologic review of
      a case of FNS was also performed. RESULTS: Thirty-three patients with FNS were
      identified. Mean age was 44 years, and 61% (n = 21) were female. Nine patients
      had tumors involving the IAC facial nerve, whereas 24 had distal tumors without
      IAC involvement. Eleven patients (33%) had hearing loss, and 55% of patients with
      sensorineural hearing loss (SNHL) had tympanic segment tumors without IAC
      involvement. The presence of SNHL was not associated with IAC tumor location (P =
      0.21). Maximal dimensions of FNSs were 3 mm to 42 mm, without correlation between
      size and SNHL severity (r = -0.017, P = 0.926). Otopathologic review of an
      untreated 5-mm IAC FNS demonstrated disproportionate spiral ganglion and hair
      cell loss within the ipsilateral cochlea compared to the contralateral ear.
      CONCLUSION: Tympanic segment FNS without IAC involvement may result in SNHL.
      Tumor size is not associated with the presence or severity of SNHL. Otopathologic
      review suggests degenerative cochlear changes in FNS. Mechanisms for SNHL in
      schwannomas are likely multifactorial and may be unrelated to cochlear nerve
      compression. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1676-1682, 2017.

PMID- 27701740
TI  - Emotional Awareness Moderates the Relationship Between Childhood Abuse and
      Borderline Personality Disorder Symptom Factors.
AB  - OBJECTIVE: To examine pathways to borderline personality disorder (BPD), focusing
      on childhood abuse and emotional attention and clarity. METHOD: Among 293
      community residents (mean age = 43.1; 53.9% female), measured associations
      between the BPD symptom factors of disturbed relatedness, affective
      dysregulation, and behavioral dysregulation and (a) childhood abuse (emotional,
      physical, and sexual); (b) emotional attention and clarity; and (c) negative
      affect, using structured interviews, the Schedule for Non-Adaptive and Adaptive
      Personality-2, the Trait Meta Mood Scale, and the Positive and Negative Affect
      Scale, respectively. RESULTS: All forms of childhood abuse were associated with
      BPD symptom factors. Emotional attention and clarity moderated the effects of
      childhood physical and emotional abuse on behavioral dysregulation and disturbed
      relatedness. All results held when controlling for negative affect. CONCLUSION:
      The relations between childhood abuse and BPD are robust. Emotional attention and
      clarity may help elucidate the links between childhood abuse and BPD.

PMID- 27701742
TI  - The new Israeli feed safety law: challenges in relation to animal and public
      health.
AB  - The Israeli feed safety legislation, which came to prominence in the early 1970s,
      has undergone a major change from simple feed safety and quality regulations to a
      more holistic concept of control of feed safety and quality throughout the whole
      feed production chain, from farm to the end user table. In February 2014, a new
      law was approved by the Israeli parliament, namely the Control of Animal Feed
      Law, which is expected to enter into effect in 2017. The law is intended to
      regulate the production and marketing of animal feed, guaranteeing the safety and
      quality of animal products throughout the production chain. The responsibility on
      the implementation of the new feed law was moved from the Plant Protection
      Inspection Service to the Veterinary Services and Animal Health. In preparation
      for the law's implementation, we have characterized the various sources and
      production lines of feed for farm and domestic animals in Israel and assessed the
      current feed safety challenges in terms of potential hazards or undesirable
      substances. Moreover, the basic requirements for feed safety laboratories, which
      are mandatory for analyzing and testing for potential contaminants, are
      summarized for each of the contaminants discussed. (c) 2016 Society of Chemical
      Industry.

PMID- 27701741
TI  - Type I IFN signaling facilitates the development of IL-10-producing effector CD8+
      T cells during murine influenza virus infection.
AB  - Recent evidence has suggested that IL-10-producing effector CD8+ T cells play an
      important role in regulating excessive inflammation during acute viral
      infections. However, the cellular and molecular cues regulating the development
      of IL-10-producing effector CD8+ T cells are not completely defined. Here, we
      show that type I interferons (IFNs) are required for the development of IL-10
      producing effector CD8+ T cells during influenza virus infection in mice. We find
      that type I IFNs can enhance IL-27 production by lung APCs, thereby facilitating
      IL-10-producing CD8+ T-cell development through a CD8+ T-cell-nonautonomous way.
      Surprisingly, we also demonstrate that direct type I IFN signaling in CD8+ T
      cells is required for the maximal generation of IL-10-producing CD8+ T cells.
      Type I IFN signaling in CD8+ T cells, in cooperation with IL-27 and IL-2
      signaling, promotes and sustains the expression of IFN regulatory factor 4 (IRF4)
      and B-lymphocyte-induced maturation protein-1 (Blimp-1), two transcription
      factors required for the production of IL-10 by effector CD8+ T cells. Our data
      reveal a critical role of the innate antiviral effector cytokines in regulating
      the production of a regulatory cytokine by effector CD8+ T cells during
      respiratory virus infection.

PMID- 27701743
TI  - Causes of neuropathy in patients referred as "Idiopathic neuropathy".

PMID- 27701744
TI  - Utility Of diaphragm ultrasound in myopathy.
AB  - INTRODUCTION: Ultrasound (US) evaluation of diaphragm thickness and contractility
      is an effective tool in neurogenic diaphragm dysfunction. There are limited data
      about the value of this technique in patients with myopathy. METHODS: We
      performed a retrospective chart review of cases with electromyography (EMG) 
      confirmed myopathy and real-time US evaluation of the diaphragm. Diaphragm
      thickness and thickening ratio (maximal inspiration/expiration) were measured.
      Demographic, imaging, pathology, and genetic data were reviewed, and the clinical
      diagnosis was recorded. RESULTS: There were 19 eligible cases, of which 14
      (73.7%) had abnormal US findings. Mean diaphragm thickness was 0.12 cm (SD 0.10),
      and the mean thickening ratio was 1.29 (SD 0.35). In all cases with abnormal US
      evaluation, the thickening ratio was abnormal. There were no cases with abnormal
      thickness alone. CONCLUSIONS: US examination can detect diaphragm dysfunction in
      myopathy. It is important to measure both the baseline thickness and thickening
      ratio to maximize sensitivity. Muscle Nerve 55: 427-429, 2017.

PMID- 27701745
TI  - Revised upper limb module for spinal muscular atrophy: Development of a new
      module.
AB  - INTRODUCTION: There is a growing need for a robust clinical measure to assess
      upper limb motor function in spinal muscular atrophy (SMA), as the available
      scales lack sensitivity at the extremes of the clinical spectrum. We report the
      development of the Revised Upper Limb Module (RULM), an assessment specifically
      designed for upper limb function in SMA patients. METHODS: An international panel
      with specific neuromuscular expertise performed a thorough review of scales
      currently available to assess upper limb function in SMA. This review facilitated
      a revision of the existing upper limb function scales to make a more robust
      clinical scale. RESULTS: Multiple revisions of the scale included statistical
      analysis and captured clinically relevant changes to fulfill requirements by
      regulators and advocacy groups. CONCLUSIONS: The resulting RULM scale shows good
      reliability and validity, making it a suitable tool to assess upper extremity
      function in the SMA population for multi-center clinical research. Muscle Nerve
      55: 869-874, 2017.

PMID- 27701746
TI  - Optimization of polyphenol removal from kiwifruit juice using a macroporous
      resin.
AB  - BACKGROUND: The separation of polyphenols from kiwifruit juice is essential for
      enhancing sensory properties and prevent the browning reaction in juice during
      processing and storage. RESULTS: The present study investigated the dynamic
      adsorption and desorption of polyphenols in kiwifruit juice using AB-8 resin. The
      model obtained could be successfully applied to predict the experimental results
      of dynamic adsorption capacity (DAC) and dynamic desorption quantity (DDQ). The
      results showed that dynamic adsorption of polyphenols could be optimised in a
      juice concentration of 19  degrees Brix, with a feed flow-rate of 1.3 mL min-1
      and a feed volume of 7 bed volume (BV). The optimum conditions for dynamic
      desorption of polyphenols from the AB-8 resin were an ethanol concentration of
      43% (v/v), an elute flow-rate of 2.2 mL min-1 and an elute volume of 3 BV. The
      optimized DAC value was 3.16 g of polyphenols kg-1 resin, whereas that for DDQ
      was 917.5 g kg-1 , with both values being consistent with the predicted values
      generated by the regression models. The major polyphenols in the dynamic
      desorption solution consisted of seven compositions. CONCLUSION: The present
      study could be scaled-up using a continuous column system for industrial
      application, thus contributing to the improved flavor and color of kiwifruit
      juice. (c) 2016 Society of Chemical Industry.

PMID- 27701747
TI  - Oral appliances and functional orthopaedic appliances for obstructive sleep
      apnoea in children.
AB  - BACKGROUND: Apnoea is a breathing disorder marked by the absence of airflow at
      the nose or mouth. In children, risk factors include adenotonsillar hypertrophy,
      obesity, neuromuscular disorders and craniofacial anomalies. The most common
      treatment for obstructive sleep apnoea syndrome (OSAS) in childhood is adeno
      tonsillectomy. This approach is limited by its surgical risks, mostly in children
      with comorbidities and, in some patients, by recurrence that can be associated
      with craniofacial problems. Oral appliances and functional orthopaedic appliances
      have been used for patients who have OSAS and craniofacial anomalies because they
      hold the lower jaw (mandible) forwards which potentially enlarges the upper
      airway and increases the upper airspace, improving the respiratory function.
      OBJECTIVES: To assess the effects of oral appliances or functional orthopaedic
      appliances for obstructive sleep apnoea in children. SEARCH METHODS: We searched
      the following electronic databases: Cochrane Oral Health's Trials Register (to 7
      April 2016); Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue
      3) in the Cochrane Library (searched 7 April 2016); MEDLINE Ovid (1946 to 7 April
      2016); Embase Ovid (1980 to 7 April 2016); LILACS BIREME (from 1982 to 7 April
      2016); BBO BIREME (from 1986 to 7 April 2016) and SciELO Web of Science (from
      1997 to 7 April 2016). We searched ClinicalTrials.gov and the World Health
      Organization International Clinical Trials Registry Platform for ongoing trials
      on 7 April 2016. We placed no restrictions on the language or date of publication
      when searching the electronic databases. SELECTION CRITERIA: All randomised or
      quasi-randomised controlled trials comparing all types of oral and functional
      orthopaedic appliances with placebo or no treatment, in children 15 years old or
      younger. PRIMARY OUTCOME: reduction of apnoea to less than one episode per hour.
      SECONDARY OUTCOMES: dental and skeletal relationship, sleep parameters
      improvement, cognitive and phonoaudiological function, behavioural problems,
      quality of life, side effects (tolerability) and economic evaluation. DATA
      COLLECTION AND ANALYSIS: Two review authors screened studies and extracted data
      independently. Authors were contacted for additional information. We calculated
      risk ratios with 95% confidence intervals for all important dichotomous outcomes.
      We assessed the quality of the evidence of included studies using GRADEpro
      software. MAIN RESULTS: The initial search identified 686 trials. Only one trial,
      reporting the results from a total of 23 children and comparing an oral appliance
      to no treatment, was suitable for inclusion in the review. The trial assessed
      apnoea-hypopnoea, daytime symptoms (sleepiness, irritability, tiredness, school
      problems, morning headache, thirstiness in the morning, oral breathing and nasal
      stuffiness) and night-time symptoms (habitual snoring, restless sleep and
      nightmares measured by questionnaire). Results were inconsistent across outcomes
      measures and time points. The evidence was considered very low quality. AUTHORS'
      CONCLUSIONS: There is insufficient evidence to support or refute the
      effectiveness of oral appliances and functional orthopaedic appliances for the
      treatment of obstructive sleep apnoea in children. Oral appliances or functional
      orthopaedic appliances may be considered in specified cases as an auxiliary in
      the treatment of children who have craniofacial anomalies which are risk factors
      for apnoea.

PMID- 27701748
TI  - Effect of high hydrostatic pressure on the polyphenols and antioxidant activity
      of plantain pulp (Musa paradisiaca AAB).
AB  - BACKGROUND: The impact of high-pressure processing (HPP) on the polyphenol (PP)
      content and antioxidant activity (AOX) of plantain pulp was evaluated. Pressures
      of 400, 500 and 600 MPa were applied to plantain pulp for 90 and 180 s at room
      temperature (25  degrees C). Polyphenoloxidase activity, extractable (EPP) and
      non-extractable PP (NEPP) contents, flavonoid content and AOX (FRAP, ABTS*+ )
      were evaluated. In addition, PP identification was performed using high
      performance liquid chromatography. RESULTS: Polyphenoloxidase activity was
      inhibited after HPP under all of the conditions studied. Increases of 110.80% and
      137.40% in EPP content under conditions of 500 MPa/180 s and 600 MPa/90 s were
      observed with a simultaneous improvement in the AOX with increments of up to
      128.71%. The treatment under conditions of 500 MPa/90 s had the highest total PP
      content, including the highest content of flavonoids (0.22 g ellagic acid
      equivalents kg-1  dry weight) and the proportion of NEPP that contained
      hydrolysable PPs (91.12 g gallic acid equivalents kg-1  dry weight with high AOX.
      The identified PPs included catechin, quercetin, gallic and hydroxybenzoic acids.
      CONCLUSION: HPP performed at a room temperature can be used for improving the
      total content of PP compounds in plantain pulp under specific pressure and time
      conditions. (c) 2016 Society of Chemical Industry.

PMID- 27701749
TI  - Reply.

PMID- 27701750
TI  - Assessment of Respiratory Distress by the Roth Score.
AB  - INTRODUCTION: Health care demand is increasing due to greater longevity of
      patients with chronic comorbidities. This increasing demand is occurring in a
      setting of resource scarcity. To address these changes, high-value care
      initiatives, such as telemedicine, are valuable resource-preservation strategies.
      This study introduces the Roth score as a telemedicine tool that uses patient
      counting times to accurately risk-stratify dyspnea severity in terms of hypoxia.
      HYPOTHESIS: The Roth score has correlation with dyspnea severity. METHODS: This
      is a prospective, controlled-cohort study. Roth score index is measured by having
      the patient count from 1 to 30 in their native language, in a single breath, as
      rapidly as possible. The primary result of the Roth score is the duration of time
      and the highest number reached. RESULTS: There was a strongly positive
      correlation between pulse oximetry and both maximal count achieved in 1 breath (r
      = 0.67; P < 0.001) and counting time (r = 0.59; P < 0.001). For oxygen saturation
      <95%, the maximal count number area under the curve is 0.828 and counting time
      area under the curve is 0.764. Counting time >8 seconds had a sensitivity of 78%
      and specificity of 73% for pulse oximetry <95%. CONCLUSIONS: The Roth score has
      strong correlation with dyspnea severity as determined by hypoxia. This tool is
      reproducible, low resource-utilization, and amenable to telemedicine. It is not
      intended to replace full clinical workup and diagnosis of respiratory distress,
      but it is useful in risk-stratifying severity of dyspnea that warrants further
      clinical evaluation.

PMID- 27701753
TI  - Gamma aminobutyric acid (GABA) receptor agonists for acute stroke.
AB  - BACKGROUND: Gamma aminobutyric acid (GABA) receptor agonists have been shown to
      have a neuroprotectant effect in reducing infarct size and improving functional
      outcome in animal models of cerebrovascular disease. However, the sedative
      effects of GABA receptor agonists have limited their wider application in people
      with acute stroke, due to the potential risk of stupor. This is an update of a
      Cochrane review first published in 2013, and previously updated in 2014.
      OBJECTIVES: To determine the efficacy and safety of GABA receptor agonists in the
      treatment of acute stroke. SEARCH METHODS: We searched the Cochrane Stroke Group
      Trials Register (accessed March 2016), the Cochrane Central Register of
      Controlled Trials (CENTRAL) 2016, Issue 3, part of the Cochrane Library (accessed
      March 2016), MEDLINE (from 1949 to March 2016), Embase (from 1980 to March 2016),
      CINAHL (from 1982 to March 2016), AMED (from 1985 to March 2016), and 11 Chinese
      databases (accessed March 2016). In an effort to identify further published,
      unpublished, and ongoing trials we searched ongoing trials registers, reference
      lists, and relevant conference proceedings, and contacted authors and
      pharmaceutical companies. SELECTION CRITERIA: We included randomized controlled
      trials (RCTs) investigating GABA receptor agonists versus placebo for people with
      acute stroke (within 12 hours after stroke onset), with the primary outcomes of
      efficacy and safety. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened the titles and abstracts of identified records, selected
      studies for inclusion, extracted eligible data, cross-checked the data for
      accuracy, and assessed the risk of bias. MAIN RESULTS: We included five trials
      with 3838 participants (3758 analyzed). The methodological quality of the
      included trials was generally good, with an unclear risk for selection bias only.
      Four trials (N = 2909) measured death and dependency at three months for
      chlormethiazole versus placebo; pooled results did not find a significant
      difference (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.96 to 1.11). One
      trial (N = 849) measured this outcome for diazepam versus placebo (RR 0.94, 95%
      CI 0.82 to 1.07). The most frequent adverse events related to chlormethiazole
      were somnolence (RR 4.56, 95% CI 3.50 to 5.95; two trials; N = 2527) and rhinitis
      (RR 4.75, 95% CI 2.67 to 8.46; two trials; N = 2527). AUTHORS' CONCLUSIONS: This
      review provides moderate-quality evidence that fails to support the use of GABA
      receptor agonists (chlormethiazole or diazepam) for the treatment of people with
      acute stroke. More well-designed RCTs with large samples of participants with
      total anterior circulation syndrome are required to determine if there are
      benefits for this subgroup. Somnolence and rhinitis are frequent adverse events
      related to chlormethiazole.

PMID- 27701752
TI  - Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated
      peripheral neuropathies.
AB  - BACKGROUND: Serum monoclonal anti-myelin-associated glycoprotein (anti-MAG)
      antibodies may be pathogenic in some people with immunoglobulin M (IgM)
      paraprotein and demyelinating neuropathy. Immunotherapies aimed at reducing the
      level of these antibodies might be expected to be beneficial. This is an update
      of a review first published in 2003 and previously updated in 2006 and 2012.
      OBJECTIVES: To assess the effects of immunotherapy for IgM anti-MAG paraprotein
      associated demyelinating peripheral neuropathy. SEARCH METHODS: On 1 February
      2016 we searched the Cochrane Neuromuscular Specialised Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for
      randomised controlled trials (RCTs). We also checked trials registers and
      bibliographies, and contacted authors and experts in the field. SELECTION
      CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs involving
      participants of any age treated with any type of immunotherapy for anti-MAG
      antibody-associated demyelinating peripheral neuropathy with monoclonal
      gammopathy of undetermined significance and of any severity.Our primary outcome
      measures were numbers of participants improved in disability assessed with either
      or both of the Neuropathy Impairment Scale (NIS) or the modified Rankin Scale
      (mRS) at six months after randomisation. Secondary outcome measures were: mean
      improvement in disability, assessed with either the NIS or the mRS, 12 months
      after randomisation; change in impairment as measured by improvement in the 10
      metre walk time, change in a validated linear disability measure such as the
      Rasch-built Overall Disability Scale (R-ODS) at six and 12 months after
      randomisation, change in subjective clinical scores and electrophysiological
      parameters at six and 12 months after randomisation; change in serum IgM
      paraprotein concentration or anti-MAG antibody titre at six months after
      randomisation; and adverse effects of treatments. DATA COLLECTION AND ANALYSIS:
      We followed standard methodological procedures expected by Cochrane. MAIN
      RESULTS: We identified eight eligible trials (236 participants), which tested
      intravenous immunoglobulin (IVIg), interferon alfa-2a, plasma exchange,
      cyclophosphamide and steroids, and rituximab. Two trials of IVIg (22 and 11
      participants, including 20 with antibodies against MAG), had comparable
      interventions and outcomes, but both were short-term trials. We also included two
      trials of rituximab with comparable interventions and outcomes.There were very
      few clinical or statistically significant benefits of the treatments used on the
      outcomes predefined for this review, but not all the predefined outcomes were
      used in every included trial and more responsive outcomes are being developed. A
      well-performed trial of IVIg, which was at low risk of bias, showed a statistical
      benefit in terms of improvement in mRS at two weeks and 10-metre walk time at
      four weeks, but these short-term outcomes are of questionable clinical
      significance. Cyclophosphamide failed to show any benefit in the single trial's
      primary outcome, and showed a barely significant benefit in the primary outcome
      specified here, but some toxic adverse events were identified.Two trials of
      rituximab (80 participants) have been published, one of which (26 participants)
      was at high risk of bias. In the meta-analysis, although the data are of low
      quality, rituximab is beneficial in improving disability scales (Inflammatory
      Neuropathy Cause and Treatment (INCAT) improved at eight to 12 months (risk ratio
      (RR) 3.51, 95% confidence interval (CI) 1.30 to 9.45; 73 participants)) and
      significantly more participants improve in the global impression of change score
      (RR 1.86, 95% CI 1.27 to 2.71; 70 participants). Other measures did not improve
      significantly, but wide CIs do not preclude some effect. Reported adverse effects
      of rituximab were few, and mostly minor.There were few serious adverse events in
      the other trials. AUTHORS' CONCLUSIONS: There is inadequate reliable evidence
      from trials of immunotherapies in anti-MAG paraproteinaemic neuropathy to form an
      evidence base supporting any particular immunotherapy treatment. IVIg has a
      statistically but probably not clinically significant benefit in the short term.
      The meta-analysis of two trials of rituximab provides, however, low-quality
      evidence of a benefit from this agent. The conclusions of this meta-analysis
      await confirmation, as one of the two included studies is of very low quality. We
      require large well-designed randomised trials of at least 12 months' duration to
      assess existing or novel therapies, preferably employing unified, consistent,
      well-designed, responsive, and valid outcome measures.

PMID- 27701755
TI  - Nutrition and Food Science - An Obvious but Little-Appreciated Partnership:
      Lessons Learned from the Road Less Traveled.

PMID- 27701751
TI  - Fine-tuning vascular fate during endothelial-mesenchymal transition.
AB  - In the heart and other organs, endothelial-mesenchymal transition (EndMT) has
      emerged as an important developmental process that involves coordinated
      migration, differentiation, and proliferation of the endothelium. In multiple
      disease states including cancer angiogenesis and cardiovascular disease, the
      processes that regulate EndMT are recapitulated, albeit in an uncoordinated and
      dysregulated manner. Members of the transforming growth factor beta (TGFbeta)
      superfamily are well known to impart cellular plasticity during EndMT by the
      timely activation (or repression) of transcription factors and miRNAs in addition
      to epigenetic regulation of gene expression. On the other hand, fibroblast growth
      factors (FGFs) are reported to augment or oppose TGFbeta-driven EndMT in specific
      contexts. Here, we have synthesized the currently understood roles of TGFbeta and
      FGF signalling during EndMT and have provided a new, comprehensive paradigm that
      delineates how an autocrine and paracrine TGFbeta/FGF axis coordinates
      endothelial cell specification and plasticity. We also provide new guidelines and
      nomenclature that considers factors such as endothelial cell heterogeneity to
      better define EndMT across different vascular beds. This perspective should
      therefore help to clarify why TGFbeta and FGF can both cooperate with or oppose
      one another during the complex process of EndMT in both health and disease.
      Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 27701754
TI  - Sialadenitis without sialolithiasis: Prospective outcomes after sialendoscopy
      assisted salivary duct surgery.
AB  - OBJECTIVES: To prospectively assess symptoms before and after sialendoscopy
      assisted salivary duct surgery (SASDS) in patients with symptomatic sialadenitis
      without sialolithiasis. STUDY DESIGN: Prospective cohort study. METHODS: Patients
      with chronic obstructive sialadenitis without sialolithiasis (COSWS) completed
      the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire prior to SASDS
      and 3 months postoperatively. RESULTS: Of 80 consecutive patients in a 20-month
      period, 20 surveyed patients underwent SASDS for COSWS in 37 symptomatic glands.
      Major symptom improvement (> 10 COSS score reduction) was reported in 24 of 37
      (65%) of all glands, including 14 of 21 (67%) of radioactive iodine (RAI)-induced
      cases and 10 of 13 (77%) of idiopathic sialadenitis cases. A significant
      reduction in postoperative mean COSS scores was seen overall (12.6 points,
      standard deviation [SD] 19.3, P < 0.05 to a post-SASDS mean score of 26.6).
      However, 19 of 37 (51%) glands demonstrated postoperative COSS scores above 25,
      denoting persistent disease. Mean COSS score reductions in RAI-induced
      sialadenitis (12.4 points, SD 22.7, P < 0.05) and idiopathic sialadenitis (16.3
      points, SD 13.7, P < 0.005) groups were significant, with post-SASDS COSS mean
      scores of 30.6 (SD 19.8) and 20.8 (SD 13.8), respectively. Ducts with stenoses
      treated with dilation or sialodochoplasty showed significant COSS improvements of
      21.1 (SD 17.9) and 12.4 points (SD 10.7), respectively (P < 0.05). In a
      multivariate analysis, both the presence of stenosis and sialodochoplasty were
      independent predictors of complete or partial resolution (post-COSS score < 25)
      and major symptom improvement (P < 0.05). CONCLUSION: SASDS provides short-term
      symptom reduction in patients with COSWS; particularly in RAI-induced and
      idiopathic sialadenitis, and in duct stenosis amenable to dilation or
      sialodochoplasty. However, approximately half of the glands did not achieve
      meaningful symptom resolution. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1073-1079,
      2017.

PMID- 27701757
TI  - Celebrating and Communicating our Achievements.

PMID- 27701758
TI  - Prevalence of past-year dental visit among US adults, 1999-2010: comparison of
      trends and estimates between the Behavioral Risk Factor Surveillance System and
      three national surveys.
AB  - OBJECTIVES: To compare estimated prevalence of past-year dental visit (PPYDV)
      among US adults aged >=18 years from the Behavioral Risk Factor Surveillance
      System (BRFSS) to estimates from the Medical Expenditure Panel Survey (MEPS),
      National Health Interview Survey (NHIS), and National Health and Nutrition
      Examination Survey (NHANES). METHODS: We estimated PPYDV adjusted for covariates
      (age, race/ethnicity, education level, poverty status, edentulism) using BRFSS,
      MEPS, and NHIS 1999-2010, and NHANES 1999-2004. We tested trend in overall PPYDV
      for BRFSS, MEPS, and NHIS from 1999-2010. For 2002 and 2010, we calculated
      absolute differences (AD) and 95% confidence intervals (CI) in PPYDV between
      BRFSS and each of the other surveys overall and among subpopulations defined by
      covariates. We pooled NHANES 1999-2004 data for comparison with BRFSS 2002.
      RESULTS: From 1999 to 2010, BRFSS (68.5% vs. 67.5%), MEPS (43.5% vs. 39.7%), and
      NHIS (63.3% vs. 59.7%) showed small but significant decreases in overall PPYDV.
      In 2002, estimates for overall PPYDV were highest for BRFSS (70.0%) and lowest
      for MEPS (43.9%) with estimates for NHIS (61.5%) and NHANES (1999-2004: 58.1%) in
      between; the largest AD (26.2%, 95% CI: 25.0%-27.3%) was between BRFSS and MEPS.
      ADs were consistent in 2002 and 2010, overall and by covariates, except among
      edentate persons, where PPYDV estimates from BRFSS and NHIS were similar.
      CONCLUSIONS: Estimates of PPYDV from BRFSS were notably higher than estimates
      from MEPS, NHIS, or NHANES except among the edentate. Trends in PPYDV over time,
      however, were consistent across all surveys.

PMID- 27701759
TI  - Spurious reticulocyte profiles in dogs with large form babesiosis: a
      retrospective study.
AB  - BACKGROUND: Erroneously high reticulocyte counts (pseudoreticulocytosis) have
      been reported in dogs with leukemia. Pseudoreticulocytosis and an abnormal
      reticulocyte profile were observed in a dog with large form babesiosis presented
      at our institution. OBJECTIVES: The aims of this retrospective study were to
      determine if dogs with babesiosis and other dogs had abnormal reticulocyte
      profiles, and to correlate these profiles with the primary diagnosis. METHODS:
      All canine CBCs obtained with the Sysmex XT-2000iV or Procyte DX were reviewed.
      Cases of large form babesiosis were identified and their reticulocyte dot plots
      were analyzed. Dogs with abnormal reticulocyte profiles but without
      microscopically apparent intraerythrocytic Babesia piroplasms were identified.
      The reticulocyte profiles and fluorescence ratios of dogs with and without
      babesiosis were compared. RESULTS: Twenty of 92 dogs with babesiosis had abnormal
      reticulocyte profiles, including 8 with a separation between the reticulocyte and
      mature RBC plots or a continuum of reticulocytes from the RBC plot but with a
      higher density of dots in the middle of the "comet tail" than in the left quarter
      of the dot plot. Thirteen of 6980 dogs without Babesia on the blood smear had
      abnormal reticulocyte profiles, including 3 with leukemia. The medium
      fluorescence reticulocyte ratios tended to be higher in dogs with babesiosis and
      abnormal dot plots than in other dogs, whereas the high-fluorescence ratio was
      higher in one dog with leukemia. CONCLUSION: Abnormal reticulocyte dot plots and
      atypical reticulocyte fluorescence ratios may occur in dogs with babesiosis and
      alert clinical pathologists to consider this diagnosis.

PMID- 27701761
TI  - Transudate or exudate: can lactate dehydrogenase activity in canine and feline
      effusions help to differentiate between the 2?
AB  - BACKGROUND: Lactate dehydrogenase (LDH) activity is often measured in human
      effusions to help in differentiating between transudates and exudates. Few
      studies have been performed using effusion samples from animals. OBJECTIVES: The
      purpose of the study was to determine whether LDH can be used to differentiate
      between transudative and exudative effusions in dogs and cats (including
      postmortem samples), and whether there is a difference between different
      laboratory methods of LDH measurement. METHODS: Lactate dehydrogenase activity
      was measured in canine and feline effusions that were submitted to the Murdoch
      University Veterinary Hospital Clinical Pathology Laboratory over approximately
      12 months using 2 wet and one dry chemistry methods, including 10 effusions
      collected postmortem. Results were compared to classification using traditional
      methods for effusion types. RESULTS: Lactate dehydrogenase activity was
      significantly higher in exudates than in transudates, significantly different
      depending on the method of measurement, and significantly higher in all effusions
      collected postmortem. An LDH effusion:serum ratio of < 0.5 was associated with
      transudates. There was no significant difference between samples collected into
      EDTA or plain serum tubes, in frozen and thawed samples, or after storage at 4
      degrees C for 3-7 days. CONCLUSIONS: Measurement of LDH activity may be useful in
      helping to differentiate between transudates and exudates in cats and dogs. The
      method of measurement must be known and kept consistent if cutoff values are to
      be used. The LDH activity was increased in all effusions collected from animals
      after death, potentially invalidating its use postmortem.

PMID- 27701760
TI  - Chronic granulomatous disease: Clinical, functional, molecular, and genetic
      studies. The Israeli experience with 84 patients.
AB  - Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic
      defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase
      components. This leads to decreased reactive oxygen species (ROS) production,
      which renders patients susceptible to life-threatening infections. Over the
      course of 30 years, we diagnosed CGD in 84 patients from 61 families using
      functional, molecular, and genetic studies. The incidence of CGD in Israel is
      1.05 per 100,000 live-births in the Jewish population and 1.49 in the Israeli
      Arab population. We diagnosed 52 patients (62%) with autosomal recessive
      inheritance (AR-CGD) and 32 (38%) with X-linked recessive inheritance (XLR-CGD).
      Consanguinity was detected in 64% of AR-CGD families (14% in Jews and 50% in
      Israeli Arabs). We found 36 different mutations (23 in XLR-CGD and 13 in AR-CGD
      patients), 15 of which were new. The clinical spectrum of CGD varied from mild to
      severe disease in both XLR and AR forms, although the AR subtype is generally
      milder. Further, residual ROS production correlated with milder clinical
      expression, better prognosis and improved overall survival. Patients with
      recurrent pyogenic infections developed fibrosis and hyperinflammatory states
      with granuloma formation. The management of CGD has progressed substantially in
      recent years, evolving from a fatal disease of early childhood to one of long
      term survival. Our present cohort displays an encouraging 81% overall long term
      survival. Early hematopoietic stem cell transplantation is advisable before
      tissue damage is irreversible. Successful transplantation was performed in 18/21
      patients. Therapeutic gene modification could become an alternative cure for CGD.
      Am. J. Hematol. 92:28-36, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701762
TI  - Impact of intravesical onabotulinumtoxinA on sexual function in women with OAB.
AB  - AIMS: Urgency urinary incontinence (UUI), and the symptoms of overactive bladder
      (OAB) have a negative impact on female sexual function. The aim of this study was
      to investigate the effect of intravesical onabotulinumtoxinA (Botox) injection on
      sexual function in women with OAB, using the multi domain Female Sexual Function
      Index (FSFI) questionnaire. METHODS: Sixty-eight sexually active women with
      idiopathic OAB with at least one episode of UUI and >=8 micturitions per 24 h
      were recruited. Patients completed the FSFI questionnaire before and 12 weeks
      after treatment with intravesical onabotulinumtoxinA injections. Baseline scores
      were compared with a control group of age-matched healthy women. RESULTS: Fifty
      six women completed the study. At baseline OAB patients reported decreased
      quality of sexual function in all domains measured with FSFI, in comparison to
      healthy women (median 21.8 vs. 26.3, P < 0.001). Over 90% of participants
      reported clinically relevant improvements in sexual function, with statistically
      significant changes in mean scores in all six domains. CONCLUSIONS: Intravesical
      Botox injections provide improvement in sexual function in women with OAB.
      Neurourol. Urodynam. 9999:XX-XX, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701763
TI  - Limited additive value of the Ki-67 proliferative index on patient survival in
      World Health Organization-classified pulmonary carcinoids.
AB  - AIMS: Currently pulmonary carcinoids are separated into typical and atypical
      based on mitotic count and presence of necrosis, according to the World Health
      Organization. At variance with gastroenteropancreatic neuroendocrine tumours,
      which are graded based on mitotic count and Ki-67 proliferative index, the use of
      Ki-67 for grading pulmonary carcinoids is still under debate. METHODS AND
      RESULTS: In this study we evaluated the prognostic impact of Ki-67 assessment in
      a multicentre cohort of 201 carcinoids [147 typical carcinoids (TCs) and 54
      atypical carcinoids (ACs)] using manual analysis (2000 cells counted) and digital
      image analysis (in-house Leica Qwin program; >=4500 cells counted). The Ki-67
      proliferative index was correlated with overall survival by means of univariate
      analysis and in comparison to clinical data by means of multivariable analysis.
      The Ki-67 index was significantly higher in ACs than in TCs for both counting
      methods (P <= 2.7e-5 ). In addition, using cut-offs of 2.5% and 4% (manual
      counting) or 1% and 5% (digital analysis), the highest differences in overall
      survival were observed (P <= 0.0067). Nevertheless, histopathological
      classification into TCs and ACs showed an equally strong association with disease
      outcome, although Ki-67 had some additive value within TCs. Ki-67 index was not
      an independent predictor of survival in multivariable analysis. CONCLUSIONS: Our
      study demonstrates that, although Ki-67 is a strong prognostic factor for
      pulmonary carcinoids, its usefulness in addition to histopathology in prediction
      of prognosis is limited. None the less, it may have additional value, especially
      in cases that are difficult to classify, in combination with histopathology and
      other molecular markers.

PMID- 27701764
TI  - Modeling and minimizing CAPRI round 30 symmetrical protein complexes from CASP-11
      structural models.
AB  - Many of the modeling targets in the blind CASP-11/CAPRI-30 experiment were
      protein homo-dimers and homo-tetramers. Here, we perform a retrospective docking
      based analysis of the perfectly symmetrical CAPRI Round 30 targets whose crystal
      structures have been published. Starting from the CASP "stage-2" fold prediction
      models, we show that using our recently developed "SAM" polar Fourier symmetry
      docking algorithm combined with NAMD energy minimization often gives acceptable
      or better 3D models of the target complexes. We also use SAM to analyze the
      overall quality of all CASP structural models for the selected targets from a
      docking-based perspective. We demonstrate that docking only CASP "center"
      structures for the selected targets provides a fruitful and economical docking
      strategy. Furthermore, our results show that many of the CASP models are dockable
      in the sense that they can lead to acceptable or better models of symmetrical
      complexes. Even though SAM is very fast, using docking and NAMD energy
      minimization to pull out acceptable docking models from a large ensemble of
      docked CASP models is computationally expensive. Nonetheless, thanks to our SAM
      docking algorithm, we expect that applying our docking protocol on a modern
      computer cluster will give us the ability to routinely model 3D structures of
      symmetrical protein complexes from CASP-quality models. Proteins 2017; 85:463
      469. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701765
TI  - Diagnostic accuracy of Wright-Giemsa and rhodanine stain protocols for detection
      and semi-quantitative grading of copper in canine liver aspirates.
AB  - BACKGROUND: Canine hepatic copper content has been increasing. Recognition of
      canine copper-associated hepatopathies is becoming more common. OBJECTIVES: The
      purpose of the study was to assess the diagnostic performance of Wright-Giemsa
      (WG) and rhodanine staining for detection of increased canine hepatic copper
      following a proposed cytologic protocol for semi-quantitative evaluation of liver
      aspirates and the effect of previous WG staining. METHODS: Retrospectively, 40
      canine hepatic WG-stained cytology cases were rhodanine stained. Diagnostic
      performance of WG staining for increased hepatic copper was evaluated. A
      rhodanine-stained cytologic copper grading system was developed. Prospectively,
      67 canine liver samples with quantitative copper measurement, a WG-then rhodanine
      stained slide, and a non-WG rhodanine-stained slide were used to assess the
      performance of the grading system and the effect of previous WG staining.
      RESULTS: Copper was not described in 40 retrospective cases on initial cytologic
      evaluation; 8/40 cases had increased copper content after rhodanine staining or
      quantitative copper assessment. Prior WG staining and destaining significantly
      affected the cytologic copper grade but not the diagnostic performance as
      measured by receiver-operating characteristic curve analysis. Quantitative copper
      concentration and previously WG-stained copper grade were moderately correlated
      (n = 67, rho = .79 [.68-.87]). For detection of >= 600 ppm, dry weight (dw)
      copper, sensitivity was .75 and specificity was .97. For detection of >= 1500
      ppm, dw copper, sensitivity was 1.0 and specificity was .97. CONCLUSIONS: Wright
      Giemsa staining alone does not reliably detect hepatic copper. Grading of
      rhodanine-stained canine hepatic cytologic samples demonstrates acceptable
      diagnostic performance for detection of copper content.

PMID- 27701766
TI  - Translation and reliability and validity testing of a Japanese version of the
      Intermittent Self-Catheterization Questionnaire among disposable and reusable
      catheter users.
AB  - AIMS: Quality of life in the context of intermittent self-catheterization varies
      depending on the type of catheter used. This study translated into Japanese,
      evaluated the feasibility, reliability, and validity of the Intermittent Self
      Catheterization Questionnaire (ISC-Q) among users of both reusable and disposable
      catheters, and examined the differences of it between them. METHODS: Seventy
      patients (age mean +/- SD: 62.8 +/- 17.7 years) completed the Japanese version of
      the ISC-Q (J-ISC-Q) at baseline and 4 weeks later. Spearman's correlation
      coefficients between the J-ISC-Q, and Qualiveen(r) and the SF-12 were used for
      the translated scale's discriminant and convergent validity. Reliability was
      evaluated by intraclass correlation coefficients (ICC), the Bland-Altman method,
      and Cronbach's alpha. RESULTS: Participants answered all questionnaire items with
      no difficulties. Scores on the convenience domain were significantly higher among
      reusable compared to disposable catheter users (P = 0.039). The J-ISC-Q had
      significantly strong correlations with the Qualiveen(r) total scale (rho = -0.712
      to -0.237), but weak correlations with the SF-12 total scale (rho = -0.231 to
      0.474). Internal consistency was good (Cronbach's alphas > 0.706), and test
      retest reliability was acceptable (ICC > 0.6) for the total scale and the four J
      ISC-Q domains. The Bland-Altman analysis showed no systematic error between
      scores at baseline and 4 weeks later for the total scale and four domains of the
      J-ISC-Q. CONCLUSIONS: The J-ISC-Q has acceptable reliability and validity for
      assessing both reusable and disposable catheter users, and can be used to promote
      tailored individualized interventions based on the impact of catheter use.

PMID- 27701767
TI  - Hematologic and biochemical reference intervals of free-living Red-Tailed Amazon
      parrot (Amazona brasiliensis) nestlings on Rasa Island, Parana, Brazil.
AB  - BACKGROUND: The Red-Tailed Amazon parrot (Amazona brasiliensis) is an endangered
      species of the Psittaciformes. There is little information about hematologic and
      biochemical variables of this species. OBJECTIVES: The purpose of this study was
      to determine hematologic and biochemical RIs for free-living A brasiliensis
      nestlings on Rasa Island, Parana, Brazil, and to compare the results between
      sexes. METHODS: Thirty-seven parrots were taken from their nests and physically
      restrained for clinical examination and blood collection. The sex was diagnosed
      by PCR using the blood samples collected. Reference intervals were determined as
      recommended by the ASVCP guidelines in healthy nestlings. The difference between
      groups was analyzed using the Mann-Whitney test or Student's t-test. RESULTS:
      Sexing revealed 12 females and 25 males. The RIs for the measured variables were
      as follows: RBC 1.1-2.6 * 106 /MUL, PCV 29.1-50.3%, HGB 7.2-12.9 g/dL, MCV 152
      293 fL, MCHC 22.2-28.4 g/dL, WBC 4.9-28.5 * 103 /MUL, 1.2-16 * 103 /MUL,
      lymphocytes 2.4-18.7 * 103 /MUL, monocytes 0.0-1.0 * 103 /MUL, eosinophils 0.0
      0.9 * 103 /MUL, 0.0-1.3 * 103 /MUL, heterophil:lymphocyte ratio 0.0-2.2, plasma
      total solids 2.1-3.7 g/dL, uric acid 0.5-2.0 mg/dL, glucose 184.9-284.3 mg/dL,
      AST 100.3-226.6 U/L, LDH 178.1-927.7 U/L, CK 149.8-1144.0 U/L, cholesterol 137.5
      256.9 mg/dL, total protein 1.8-3.0 g/dL, calcium 7.0-8.6 mg/dL, and phosphorus
      2.9-6.1 mg/dL. Increased concentrations of cholesterol (P < .05) were observed in
      females. DISCUSSION: This is the first study to establish hematologic and
      biochemical RIs for free-living A brasiliensis nestlings on Rasa Island.
      Hematologic and biochemical variables are important tools for evaluating the
      health status of free-living birds, and also support conservation planning for
      endangered species.

PMID- 27701768
TI  - Double phosphorylation-induced structural changes in the signal-receiving domain
      of IkappaBalpha in complex with NF-kappaB.
AB  - Activation of the transcription factor NF-kappaB requires degradation of its
      physiological inhibitor IkappaBalpha in order to allow nuclear translocation of
      NF-kappaB. NF-kappaB activity links inflammation and carcinogenesis and makes its
      signaling pathway an important target for therapeutic intervention. The signal
      receiving N-terminal domain (SRD) of the NF-kappaB inhibitor IkappaBalpha harbors
      the sites of post-translational modifications (Ser32 and 36) directed by the
      IkappaB kinase (IKK) complex. The SRD was originally recognized to be highly
      disordered, but was recently shown to possess stable secondary structural
      elements. Identifying and characterizing the structural effects that arise from
      phosphorylation may explain how phosphorylation regulates the IkappaBalpha-NF
      kappaB protein complex. Therefore, the effect of post-translational mono- and
      double-phosphorylation of the serine residues of the SRD was analyzed. The
      structural modifications of the IkappaBalpha-NF-kappaB protein-protein complex
      due to mono-phosphorylation of either Ser32 or Ser36 amino acid residues or
      simultaneous phosphorylation were investigated by means of molecular dynamics
      simulations. Mono-phosphorylation at either Ser32 or Ser36 was not sufficient to
      induce significant structural changes in the secondary structure of the SRD of
      IkappaBalpha. Double-phosphorylation yielded an increase in distance between the
      Calpha atoms of these serine residues, indicative of a structural change. Only
      this two-fold phosphorylation induced the extended, more stabilized conformation
      of the degron motif which renders it accessible by the E3 ligase. In summary,
      these results provide insight into the conformational changes induced in
      IkappaBalpha proteins upon phosphorylation that are vital to their signaling
      dynamics and enable us to propose a model for the phosphorylation of the SRD.
      Proteins 2016; 85:17-29. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701769
TI  - Incontinence in persons with Down Syndrome.
AB  - AIMS: To assess the rates of incontinence and associated psychological problems
      in children, adolescents and adults with Down Syndrome, a genetic syndrome caused
      by partial or complete triplication (trisomy) of chromosome 21 and characterized
      by typical facial features, a physical growth delay and mild or moderate
      intellectual disability. METHODS: Three hundred and seventeen persons with Down
      Syndrome (4-51 years) were recruited through a German parent support group (59.6%
      male, mean age 19.2 years). The Parental Questionnaire: Enuresis/Urinary
      Incontinence, the Incontinence Questionnaire-Pediatric Lower Urinary Tract
      Symptoms, as well as the Developmental Behavior Checklist (DBC) for parents or
      for adults were filled out by parents or care-givers. RESULTS: 17.2% of the
      sample had nocturnal enuresis, 15.9% had daytime urinary incontinence, and 14.2%
      had fecal incontinence. Incontinence was present in 64.0% of young children (4-12
      years), 10.3% of teens (13-17 years), 12.8% of young adults (18-30 years) and in
      22.4% of older adults (>30 years). 13.6% of children and 8.4% of adults had a DBC
      score in the clinical range. 19.5% of children and 27.8% of adults with
      incontinence had behavioral problems. There was a significant association between
      nocturnal enuresis, daytime urinary incontinence and clinical DBC scores in
      adults. CONCLUSIONS: Incontinence in Down Syndrome is mainly present in young
      children and increases in older adults. Behavioral comorbidity is associated with
      incontinence only in adults with Down Syndrome. Screening and treatment of
      incontinence in individuals with Down Syndrome is recommended.

PMID- 27701770
TI  - Risk factors for infections in myelofibrosis: role of disease status and
      treatment. A multicenter study of 507 patients.
AB  - Although infectious complications represent a relevant cause of morbidity and
      mortality in patients with myelofibrosis (MF), little is known about their
      incidence, outcome and risk factors. We retrospectively evaluated a cohort of 507
      MF patients, diagnosed between 1980 and 2014 in five Italian hematology centers,
      to define the epidemiology of infections and describe the impact of ruxolitinib
      (RUX) treatment. Overall, 112 patients (22%) experienced 160 infectious events
      (grade 3-4, 45%) for an incidence rate of 3.9% per patient-year. Infections were
      mainly bacterial (78%) and involving the respiratory tract (52% of cases). Also,
      viral (11%) and fungal infections (2%) were recorded. Overall, infections were
      fatal in 9% of the cases. Among baseline features, high/intermediate-2 IPSS
      category (HR 1.8, 95%CI:1.2-2.7; P = 0.02) and spleen length >=10 cm below left
      costal margin (HR 1.6, 95%CI:1.1-2.5; P = 0.04) were associated with higher
      infectious risk in multivariate analysis. Overall, the rate of infections was
      higher in the cohort of 128 RUX-treated patients (44% vs. 20%, P < 0.001). In
      conclusion, IPSS-category and splenomegaly, emerged as the main risk factors for
      infections in MF. RUX-treated patients experienced significantly more infection
      episodes; however, future prospective studies are needed to isolate the
      confounding contribution of other risk factors such as disease stage. Am. J.
      Hematol. 92:37-41, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701771
TI  - Antibiotics in the first year of life and subsequent neurocognitive outcomes.
AB  - AIM: There may be a link between disruption to the gut microbiota in early life
      and later neurocognitive outcomes. We hypothesised that antibiotic use in early
      life is associated with a detrimental effect on later neurocognitive outcomes.
      METHODS: Eight hundred and seventy-one European mothers and their children
      enrolled in the Auckland Birthweight Collaborative Study at birth. Information on
      antibiotic use during the first year of life and between 12 months and three-and
      a-half years of age was gathered via maternal interview. Intelligence test scores
      and measures of behavioural difficulties were obtained when children were three
      and-a-half years, seven years and 11 years of age. RESULTS: Antibiotic use in the
      first year of life was reported in 70% of the 526 children with antibiotic data
      assessed at age three-and-a-half years. Those who had received antibiotics had
      more behavioural difficulties and more symptoms of depression at follow-up.
      Results were consistent across all standardised psychologist administered tests,
      as well as parent rated, teacher rated and self-report measures. CONCLUSION: This
      study demonstrates an association between antibiotic use in the first year of
      life and subsequent neurocognitive outcomes in childhood. If confirmed by further
      research, these findings could have implications for the use of antibiotics for
      minor illnesses in infancy.

PMID- 27701772
TI  - Effects of an alpha1A/D-adrenoceptor antagonist, naftopidil, and a
      phosphodiesterase type 5 inhibitor, tadalafil, on urinary bladder remodeling in
      rats with spinal cord injury.
AB  - AIMS: In order to clarify whether an alpha1A/D-adrenoceptor (alpha1 A/D-AR)
      antagonist, naftopidil, or a phosphodiesterase type 5 (PDE5) inhibitor,
      tadalafil, prevents bladder wall remodeling after spinal cord injury (SCI), we
      examined the bladder and urethral activity as well as ischemic and fibrotic
      changes in the bladder using SCI rats with or without naftopidil or tadalafil
      treatment. METHODS: Adult female Sprague-Dawley rats were divided into four
      groups: (1) normal (spinal cord intact); (2) vehicle SCI; (3) naftopidil SCI; and
      (4) tadalafil SCI groups. In SCI groups, rats underwent Th9-10 spinal cord
      transection followed by oral application of vehicle, naftopidil (20 mg/kg/day) or
      tadalafil (2 mg/kg/day) for 1, 2, 4, 8, and 12 weeks. Bladder and urethral
      pressures, mRNA levels of fibrosis-related molecules and ischemia markers and the
      composition of bladder collagen and elastin were evaluated. RESULTS: Naftopidil
      treatment reduced the upregulation of mRNA levels of ischemia and fibrosis
      markers at the early phase of SCI, and ameliorated the decrease of bladder
      compliance and voiding efficiency, and the increase of urethral pressure and
      collagen concentration in the bladder wall at the late phase of SCI. Tadalafil
      treatment reduced the upregulation of mRNA levels of fibrosis markers, the
      decrease of bladder compliance and the increase of collagen concentration at the
      late phase of SCI. CONCLUSIONS: These results suggest that naftopidil and
      tadalafil treatments improved the bladder remodeling shown by increased bladder
      collagen contents after SCI in a different time course. Thus, these treatments
      could be effective for reducing the SCI-related tissue remodeling in the bladder.
      Neurourol. Urodynam. 9999:XX-XX, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701773
TI  - Dissemination and Implementation Research in Marriage and Family Therapy: An
      Introduction and Call to the Field.
AB  - Despite the considerable resources allocated to research to promote public
      health, interventions capable of benefiting individuals and families are not
      finding their way into regular practice. An important avenue for addressing this
      problem is through dissemination and implementation (D&I) science, a burgeoning
      research area focusing on translating empirical knowledge into everyday practice.
      This article begins by suggesting ways in which MFTs are uniquely equipped to
      contribute to and benefit from D&I research. We will then provide an overview of
      D&I research, outlines key D&I models, and highlight examples of family
      intervention research relevant to MFTs using the key models. Finally, we conclude
      by providing the field with important next steps to advance the presence of MFT
      research within D&I scholarship.

PMID- 27701774
TI  - Thyroid eye disease: a review.
AB  - Thyroid eye disease is a multifactorial autoimmune disease with a spectrum of
      signs and symptoms. Oftentimes, the diagnosis of thyroid eye disease is
      straightforward, based upon history and physical examination. The purpose of this
      review is to assist the eye-care practitioner in staging the severity of thyroid
      eye disease (mild, moderate-to-severe and sight-threatening) and correlating
      available treatment modalities. Eye-care practitioners play an important role in
      the multidisciplinary team by assessing functional vision while also managing
      ocular health.

PMID- 27701775
TI  - Evaluation of intraocular pressure estimates obtained using an iCare rebound
      tonometer.
AB  - BACKGROUND: The aims of this study were to evaluate the intra- and inter-observer
      repeatability of intraocular pressure (IOP) estimates obtained using an iCare
      rebound tonometer and to investigate the variation in IOP measurements due to
      positional differences in probe placement on the cornea. METHODS: The IOP
      estimates were obtained by two observers, twice on one eye, of 114 subjects using
      an iCare tonometer on the central cornea. Additionally, IOP and corneal thickness
      were measured in 38 subjects at three locations, namely, central, at 1.5 mm
      nasally and at 1.5 mm temporally from the central cornea. Agreement among
      measurements was assessed using Bland and Altman plots and the difference in
      measurements obtained by the observers was compared using paired t-test. Values
      obtained from central, nasal and temporal regions were compared using one-way
      analysis of variance. RESULTS: The mean IOP measurements obtained by observer 1
      on two attempts were 16.2 and 16.0 mmHg (p > 0.05) were significantly different
      from the IOP values obtained by observer 2 on two occasions (16.3 and 15.7 mmHg;
      p < 0.0001). The limits of agreement (LOA) of intra-observer repeatability were 
      2.9 to +2.6 mmHg and -3.4 to +2.2 for observers 1 and 2, respectively. The LOA of
      inter-observer repeatability for first and second sequences were -2.8 to +3.0
      mmHg and -3.3 to +2.7 mmHg with the second sequence of measurements being
      significantly different (p = 0.03). Although the corneal thickness was
      significantly greater nasally and temporally, when compared to the central
      location, by 32 and 20 microns respectively (p < 0.0001), the measured IOPs on
      those locations were not significantly different, when compared to the central
      measurements (p = 0.14). CONCLUSION: There is good intra- and inter-observer
      repeatability of IOP data, as obtained by the iCare rebound tonometer, although
      the results may be slightly influenced by practitioner experience. The difference
      in IOP estimates obtained by different observers is unlikely to be of clinical
      significance. Corneal thickness showed regional variation; however, this did not
      influence IOP measurements obtained from those locations.

PMID- 27701776
TI  - pyDock scoring for the new modeling challenges in docking: Protein-peptide, homo
      multimers, and domain-domain interactions.
AB  - The sixth CAPRI edition included new modeling challenges, such as the prediction
      of protein-peptide complexes, and the modeling of homo-oligomers and domain
      domain interactions as part of the first joint CASP-CAPRI experiment. Other non
      standard targets included the prediction of interfacial water positions and the
      modeling of the interactions between proteins and nucleic acids. We have
      participated in all proposed targets of this CAPRI edition both as predictors and
      as scorers, with new protocols to efficiently use our docking and scoring scheme
      pyDock in a large variety of scenarios. In addition, we have participated for the
      first time in the servers section, with our recently developed webserver,
      pyDockWeb. Excluding the CASP-CAPRI cases, we submitted acceptable models (or
      better) for 7 out of the 18 evaluated targets as predictors, 4 out of the 11
      targets as scorers, and 6 out of the 18 targets as servers. The overall success
      rates were below those in past CAPRI editions. This shows the challenging nature
      of this last edition, with many difficult targets for which no participant
      submitted a single acceptable model. Interestingly, we submitted acceptable
      models for 83% of the evaluated protein-peptide targets. As for the 25 cases of
      the CASP-CAPRI experiment, in which we used a larger variety of modeling
      techniques (template-based, symmetry restraints, literature information, etc.),
      we submitted acceptable models for 56% of the targets. In summary, this CAPRI
      edition showed that pyDock scheme can be efficiently adapted to the increasing
      variety of problems that the protein interactions field is currently facing.
      Proteins 2017; 85:487-496. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701778
TI  - The Dyadic Effects of Supportive Coparenting and Parental Stress on Relationship
      Quality Across the Transition to Parenthood.
AB  - The transition to first-time parenthood can be challenging for couples. Using a
      sample of 848 ethnically diverse couples from the Fragile Families and Child
      Wellbeing Study across the first 3 years of parenthood, we investigated the
      longitudinal and dyadic associations of each parents' parental stress, supportive
      coparenting, and relationship quality. Results from an actor-partner
      interdependence model indicated that supportive coparenting significantly
      predicted higher relationship quality for both mothers and fathers. Fathers'
      supportive coparenting significantly buffered the effects of mothers' parental
      stress on relationship quality. Also, the unique dyadic contexts of each parents'
      supportive coparenting, and also both partners' parental stress were
      significantly associated with relationship quality. Clinical implications from
      these findings are discussed through commonly used clinical theories.

PMID- 27701779
TI  - Urinary incontinence in the Netherlands: Prevalence and associated risk factors
      in adults.
AB  - AIMS: To determine the prevalence and risk factors associated with urinary
      incontinence (UI) among adults in the Netherlands. METHODS: In this cross
      sectional study, we included 1257 respondents aged >= 18 years, who completed the
      validated Groningen Defecation and Fecal Continence Checklist. UI was defined as
      any involuntary leakage of urine during the past 6 months. RESULTS: The
      prevalence of UI in the total group was 36.8%. Women experienced UI significantly
      more often than men (49.0% versus 22.6%, respectively, P < 0.001). We found that
      in both men and women, the prevalence of UI increased with aging (P = 0.003 and P
      < 0.001, respectively). Remarkably, multivariate analysis revealed that age did
      not influence UI in men. Men and women aged 18-39 also experienced UI (17.0% and
      36.1%, respectively). We established that diabetes mellitus, fecal incontinence,
      and constipation were risk factors for UI. In women, obesity, vaginal
      hysterectomies, and vaginal parturition were also risk factors for UI, as was
      prostate surgery in men. CONCLUSIONS: The prevalence of UI in the Netherlands is
      high. Medical practitioners should therefore not underestimate this problem,
      especially among young people. Because the multivariate analysis revealed that in
      men age did not correlate significantly with UI, we believe that the risk of
      experiencing UI increases with age because of diseases that are known to lead to
      UI and not because of aging as a single factor itself. Finally, this study can be
      used as a reference for patients living in Western-Europe.

PMID- 27701777
TI  - Modeling complexes of modeled proteins.
AB  - Structural characterization of proteins is essential for understanding life
      processes at the molecular level. However, only a fraction of known proteins have
      experimentally determined structures. This fraction is even smaller for protein
      protein complexes. Thus, structural modeling of protein-protein interactions
      (docking) primarily has to rely on modeled structures of the individual proteins,
      which typically are less accurate than the experimentally determined ones. Such
      "double" modeling is the Grand Challenge of structural reconstruction of the
      interactome. Yet it remains so far largely untested in a systematic way. We
      present a comprehensive validation of template-based and free docking on a set of
      165 complexes, where each protein model has six levels of structural accuracy,
      from 1 to 6 A Calpha RMSD. Many template-based docking predictions fall into
      acceptable quality category, according to the CAPRI criteria, even for highly
      inaccurate proteins (5-6 A RMSD), although the number of such models (and,
      consequently, the docking success rate) drops significantly for models with RMSD
      > 4 A. The results show that the existing docking methodologies can be
      successfully applied to protein models with a broad range of structural accuracy,
      and the template-based docking is much less sensitive to inaccuracies of protein
      models than the free docking. Proteins 2017; 85:470-478. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27701780
TI  - Lessons from (co-)evolution in the docking of proteins and peptides for CAPRI
      Rounds 28-35.
AB  - Computational protein-protein docking is of great importance for understanding
      protein interactions at the structural level. Critical assessment of prediction
      of interactions (CAPRI) experiments provide the protein docking community with a
      unique opportunity to blindly test methods based on real-life cases and help
      accelerate methodology development. For CAPRI Rounds 28-35, we used an automatic
      docking pipeline integrating the coarse-grained co-evolution-based potential
      InterEvScore. This score was developed to exploit the information contained in
      the multiple sequence alignments of binding partners and selectively recognize co
      evolved interfaces. Together with Zdock/Frodock for rigid-body docking, SOAP-PP
      for atomic potential and Rosetta applications for structural refinement, this
      pipeline reached high performance on a majority of targets. For protein-peptide
      docking and interfacial water position predictions, we also explored different
      means of taking evolutionary information into account. Overall, our group ranked
      1st by correctly predicting 10 targets, composed of 1 High, 7 Medium and 2
      Acceptable predictions. Excellent and Outstanding levels of accuracy were reached
      for each of the two water prediction targets, respectively. Altogether, in 15 out
      of 18 targets in total, evolutionary information, either through co-evolution or
      conservation analyses, could provide key constraints to guide modeling towards
      the most likely assemblies. These results open promising perspectives regarding
      the way evolutionary information can be valuable to improve docking prediction
      accuracy. Proteins 2017; 85:378-390. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701781
TI  - Hereditary persistence of fetal hemoglobin in two patients with KLF1
      haploinsufficiency due to 19p13.2-p13.12/13 deletion.

PMID- 27701782
TI  - Reply from authors to Letter to the Editor on "RE: Konrad Futyma, Lukasz
      Nowakowski, Michal Bogusiewicz, Alicja Zietek, Andrzej P. Wieczorek and Tomasz
      Rechberger. Use of Uroflow Parameters in Diagnosing an Overactive Bladder-Back to
      the Drawing Board" manuscript number: Neurourol Urodyn DOI 10.1002/nau.22898.

PMID- 27701783
TI  - Activation of ethylene signaling pathways enhances disease resistance by
      regulating ROS and phytoalexin production in rice.
AB  - Ethylene plays diverse roles in plant growth, development and stress responses.
      However, the roles of ethylene signaling in immune responses remain largely
      unknown. In this study, we showed that the blast fungus Magnaporthe oryzae
      infection activated ethylene biosynthesis in rice. Resistant rice cultivars
      accumulated higher levels of ethylene than susceptible ones. Ethylene signaling
      components OsEIN2 and the downstream transcription factor OsEIL1 positively
      regulated disease resistance. Mutation of OsEIN2 led to enhanced disease
      susceptibility. Whole-genome transcription analysis revealed that responsive
      genes of ethylene, jasmonates (JAs) and reactive oxygen species (ROS) signaling
      as well as phytoalexin biosynthesis genes were remarkably induced. Transcription
      of OsrbohA/B, which encode NADPH oxidases, and OsOPRs, the JA biosynthesis genes,
      were induced by M. oryzae infection. Furthermore, we demonstrated that OsEIL1
      binds to the promoters of OsrbohA/OsrbohB and OsOPR4 to activate their
      expression. These data suggest that OsEIN2-mediated OsrbohA/OsrbohB and OsOPR
      transcription may play essential roles in ROS generation, JA biosynthesis and the
      subsequent phytoalexin accumulation. Therefore, the involvement of ethylene
      signaling in disease resistance is probably by activation of ROS and phytoalexin
      production in rice during M. oryzae infection.

PMID- 27701784
TI  - Infectious morbidity and resource use in children under 2 years old at childcare
      centres.
AB  - AIM: To analyse the associations between childcare centres and infectious
      morbidity and resource consumption. METHODS: Cohort study from birth to 2 years.
      OUTCOME VARIABLE: number and types of infections, drug consumption and medical
      visits. Exposure variable: attending or not attending a childcare centre. School
      age: 6-12, >12-18, >18-24 months. RESULTS: The initial cohort comprised 445
      children, and the final cohort comprised 419 children. The mean number of
      recurrent infections and wheezing was higher in children attending childcare
      centres in all age groups with significant differences. Recurrent acute otitis
      media was observed in the 12- to 18-month group with an odds ratio of 6.04 (95%
      confidence interval, 1.3-27.6; P = 0.001) in the children attending childcare
      centres. In children older than 6 months, there was greater consumption of
      antibiotics, inhaled bronchodilators, oral and inhaled corticosteroids and
      montelukast. CONCLUSIONS: Attending a childcare is associated with an increased
      frequency of recurrent infections and wheezing, as well as the consumption of
      antibiotics, bronchodilators, corticosteroids and montelukast.

PMID- 27701785
TI  - Paediatric lymphoedema: A retrospective chart review of 86 cases.
AB  - AIM: To define the clinical characteristics, investigations, management and
      outcomes of lymphoedema in a paediatric cohort. METHODS: A retrospective chart
      review of children with lymphoedema seen at two tertiary paediatric hospitals
      since 1998. Telephone interviews with parents were performed when information was
      missing. Information recorded included demographic data, features of diagnosis
      and clinical presentation, symptoms, complications and treatment. RESULTS: A
      total of 86 patients with lymphoedema were identified. Eighty cases (93%) were
      primary and six cases (7%) were secondary. Most were female (60%). Location of
      swelling was most commonly the lower limbs (94%). There were 13 cases (15%) of
      genital involvement. Swelling presented in the first 12 months of life in 60% of
      primary lymphoedema patients. Complications of lymphoedema occurred in 73% of
      patients. Lymphoscintigraphy was the most common investigation used (65%),
      followed by ultrasound (57%) and magnetic resonance imaging (MRI) (35%). Eight of
      the 48 (17%) lymphoscintigraphs produced a false negative result or were
      inconclusive with a correct diagnosis subsequently made clinically and using MRI.
      Average time to diagnosis was 9 months. Lymphoedema was managed with compression
      garments (99%), manual lymph drainage (97%) and multilayered bandaging (68%).
      Eight patients had an operative procedure as a part of management. CONCLUSIONS:
      Primary lymphoedema is more common than secondary lymphoedema in children. Onset
      tends to be during infancy for both males and females, and the lower limb is
      typically involved. Causes of secondary lymphoedema are diverse and rare.
      Diagnosis in children is often delayed but is possible based on history and
      physical examination alone and when further investigation is necessary MRI is
      effective.

PMID- 27701786
TI  - Environmental enrichment and physical exercise revert behavioral and
      electrophysiological impairments caused by reduced adult neurogenesis.
AB  - It is well known that adult neurogenesis occurs in two distinct regions, the
      subgranular zone of the dentate gyrus and the subventricular zone along the walls
      of the lateral ventricles. Until now, the contribution of these newly born
      neurons to behavior and cognition is still uncertain. The current study tested
      the functional impacts of diminished hippocampal neurogenesis on emotional and
      cognitive functions in transgenic Gfap-tk mice. Our results showed that anxiety
      related behavior evaluated both in the elevated plus maze as well as in the open
      field, social interaction in the sociability test, and spatial working memory in
      the spontaneous alternation test were not affected. On the other hand,
      recognition and emotional memory in the object recognition test and contextual
      fear conditioning, and hippocampal long-term potentiation were impaired in
      transgenic mice. Furthermore, we evaluated whether environmental enrichment
      together with physical exercise could improve or even restore the level of adult
      neurogenesis, as well as the behavioral functions. Our results clearly
      demonstrated that environmental enrichment together with physical exercise
      successfully elevated the overall number of progenitor cells and young neurons in
      the dentate gyrus of transgenic mice. Furthermore, it led to a significant
      improvement in object recognition memory and contextual fear conditioning, and
      reverted impairments in hippocampal long-term potentiation. Thus, our results
      confirm the importance of adult neurogenesis for learning and memory processes
      and for hippocampal circuitry in general. Environmental enrichment and physical
      exercise beneficially influenced adult neurogenesis after it had been disrupted
      and most importantly recovered cognitive functions and long-term potentiation.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27701787
TI  - Delayed diagnosis: An important prognostic factor for oesophageal atresia in
      developing countries.
AB  - AIM: The aim of this study is to analyse the effect of delayed diagnosis on
      mortality rates, and evaluate the role of delayed diagnosis as a new prognostic
      factor in patients with oesophageal atresia (OA), especially in developing
      countries. METHODS: The records of 80 consecutive patients with OA (2008-2013)
      were reviewed. Patients were divided into two groups according to the time of
      diagnosis. As we demonstrated the effect of delayed diagnosis on mortality, we
      decided to develop a new classification that will be utilised to predict the
      prognosis of OA. The discrimination ability of the new prognostic classification
      was compared with those of the Waterston, Montreal and Spitz classifications
      using the area under the curve. RESULTS: The parameters of the new prognostic
      classification were birth weight less than 2000 g, the presence of major
      cardiac/life-threatening anomalies and delay in diagnosis. Class I consisted of
      patients with none or one of these parameters. Class II consisted of patients
      with two or three of these parameters. The area under the curve of the new
      classification was better than those of the other classifications in determining
      the prognosis of patients with OA. CONCLUSIONS: Delayed diagnosis of OA
      significantly led to morbidity and mortality. Although delayed diagnosis is not a
      characteristic of newborn or a marker of severity for OA and is a health care
      system issue in developing countries, we here point out that it is a prognostic
      factor in its own right. Our new classification has a superior discriminatory
      ability compared to the above-mentioned classifications.

PMID- 27701788
TI  - Pleiotropic function of TRPV4 ion channels in the central nervous system.
AB  - NEW FINDINGS: What is the topic of this review? In this concise review, we
      highlight insights into the role of transient receptor potential, vanilloid type
      4 (TRPV4) ion channels in the CNS, results that have been contributed over the
      last 16 years since the initial discovery of the channel. What advances does it
      highlight? TRPV4 has been found to function in neurons, astroglia and microglia,
      both in physiological (e.g. astrocytic neurovascular coupling, neuronal membrane
      potential at physiological temperature) and in pathological conditions (e.g.
      mechanical trauma), so far recorded as exciting findings in need of more in-depth
      mechanistic clarification. Transient receptor potential, vanilloid type 4 (TRPV4)
      ion channels are osmo-mechano-TRP channels, with pleiotropic function and
      expression in many different types of tissues and cells. They have also been
      found to be involved in pain and inflammation. Studies have focused on the role
      of TRPV4 in peripheral sensory neurons, but its expression and function in
      central nervous glial cells and neurons has also been documented. In this
      overview, based on the senior author's (WL) lecture at the recent recent joint
      meeting of APS/The Physiological Society in Dublin, we concisely review evidence
      of TRPV4 expression and function in the CNS and how TRPV4 function can be
      modulated for therapeutic benefit of neuropsychiatric disorders. Novel TRPV4
      inhibitory compounds developed recently in the authors' laboratory are also
      discussed.

PMID- 27701789
TI  - Acute pancreatitis complicating choledochal cysts in children.
AB  - AIM: To analyse the characteristics of patients with choledochal cysts presenting
      with acute pancreatitis. METHODS: Multicenter retrospective review of all
      paediatric patients (<18 years) with choledochal cysts managed over a 14-year
      period (2001-2014) at two tertiary paediatric surgical centres. Patient data were
      analysed for demographics, presentation, radiological classification of cyst type
      (Todani), operative interventions, complications and long-term follow-up.
      RESULTS: A total of 49 patients with choledochal cysts were identified with 15
      (31%) being Type I fusiform, 18 (37%) Type I cystic and 16 (32%) Type IV-A.
      Seventeen (35%) patients presented with acute pancreatitis, one having had an
      ante-natally diagnosed choledochal cyst. Patients presenting with pancreatitis
      were older when compared to the non-pancreatitis group (5.1 vs. 1.2 years, P =
      0.005). Nine out of 16 (53%) patients with Type IV-A cysts presented with
      pancreatitis compared to five (33%) of Type I fusiform and three (17%) of Type I
      cystic. There was however no statistically significant association between Todani
      types and the development of pancreatitis (Type I fusiform, P = 1.0; Type I
      cystic, P = 0.063; Type IV-A, P = 0.053). The rate of complications was similar
      in both groups. CONCLUSION: Pancreatitis was a common presentation in children
      with a choledochal cyst, however, there was no clear statistically significant
      association with Todani types and pancreatitis.

PMID- 27701790
TI  - Six-year trajectory of objective physical function in persons with depressive and
      anxiety disorders.
AB  - BACKGROUND: Depression and anxiety have been related to poorer self-reported
      physical functioning over time; however, objective measures of physical function
      are less frequently examined. This study assessed the 6-year trajectory of hand
      grip strength and lung function in persons with depressive and/or anxiety
      disorders. METHODS: At four waves (baseline, 2, 4, and 6 years) hand-grip
      strength and lung function were assessed in 2,480 participants, aged 18-65 years,
      of the Netherlands Study of Depression and Anxiety. Linear mixed models were used
      to examine the association between baseline psychiatric status (current and
      remitted depression and anxiety, healthy controls) and physical function during 6
      year follow-up, adjusted for sociodemographics, lifestyle, and health indicators.
      RESULTS: Although there were no differences in the rate of decline over time,
      women with current, but not remitted, depression and anxiety had poorer hand-grip
      strength (B = -1.34, P < .001) and poorer lung function (B = -11.91, P =.002)
      compared to healthy women during the entire 6-year follow-up. Associations with
      depression and anxiety severity measures confirmed dose-response relationships
      with objective physical function. In men, stronger 6-year decline of lung
      function was found in those with current disorders (current diagnosis-by-time: B
      = -11.72, P = .002) and even in those with remitted disorders (remitted diagnosis
      by time: B = -10.11, P = .04) compared to healthy men. CONCLUSIONS: Depression
      and anxiety are associated with consistently poorer hand-grip strength in women
      and poorer lung function in women and men over 6 years of time, implicating their
      long-lasting impact on physical functioning.

PMID- 27701791
TI  - Utilization of Mental Health Services by Veterans Living in Rural Areas.
AB  - PURPOSE: There is concern that veterans living in rural areas may not be
      receiving the mental health (MH) treatment they need. This study uses recent
      national survey data to examine the utilization of MH treatment among military
      veterans with a MH condition living in rural areas, providing comparisons with
      estimates of veterans living in urban areas. METHODS: Multivariable logistic
      regression is utilized to examine differences in MH service use by urban/rural
      residence, controlling for other factors. Rates of utilization of inpatient and
      outpatient treatment, psychotropic medication, any MH treatment, and perceived
      unmet need for MH care are examined. FINDINGS: There were significant differences
      in MH treatment utilization among veterans by rural/urban residence. Multivariate
      estimates indicate that compared to veterans with a MH condition living in urban
      areas, veterans in rural areas had 70% lower odds of receiving any MH treatment.
      Veterans with a MH condition in rural areas have approximately 52% and 64% lower
      odds of receiving outpatient treatment and prescription medications,
      respectively, compared to those living in urban areas. Differences in perceived
      unmet need for mental health treatment were not statistically significant.
      CONCLUSIONS: While research indicates that recent efforts to improve MH service
      delivery have resulted in improved access to services, this study found that
      veterans' rates of MH treatment are lower in rural areas, compared to urban
      areas. Continued efforts to support the provision of behavioral health services
      to rural veterans are needed. Telemedicine, using rural providers to their
      maximum potential, and engagement with community stakeholder groups are promising
      approaches.

PMID- 27701792
TI  - Active place avoidance is no more stressful than unreinforced exploration of a
      familiar environment.
AB  - Training in the active place avoidance task changes hippocampus synaptic
      function, the dynamics of hippocampus local field potentials, place cell
      discharge, and active place avoidance memory is maintained by persistent PKMzeta
      activity. The extent to which these changes reflect memory processes and/or
      stress responses is unknown. We designed a study to assess stress within the
      active place avoidance task by measuring serum corticosterone (CORT) at different
      stages of training. CORT levels did not differ between trained mice that learned
      to avoid the location of the mild foot shock, and untrained no-shock controls
      exposed to the same environment for the same amount of time. Yoked mice, that
      received unavoidable shocks in the same time sequence as the trained mice, had
      significantly higher CORT levels than mice in the trained and no-shock groups
      after the first trial. This increase in CORT disappeared by the fourth trial the
      following day, and levels of CORT for all groups matched that of home cage
      controls. The data demonstrate that place avoidance training is no more stressful
      than experiencing a familiar environment. We conclude that changes in neural
      function as a result of active place avoidance training are likely to reflect
      learning and memory processes rather than stress. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27701793
TI  - 11p15 ICR1 Partial Deletions Associated with IGF2/H19 DMR Hypomethylation and
      Silver-Russell Syndrome.
AB  - The 11p15 region harbors the IGF2/H19 imprinted domain, implicated in fetal and
      postnatal growth. Silver-Russell syndrome (SRS) is characterized by fetal and
      postnatal growth failure, and is caused principally by hypomethylation of the
      11p15 imprinting control region 1 (ICR1). However, the mechanisms leading to ICR1
      hypomethylation remain unknown. Maternally inherited genetic defects affecting
      the ICR1 domain have been associated with ICR1 hypermethylation and Beckwith
      Wiedemann syndrome (an overgrowth syndrome, the clinical and molecular mirror of
      SRS), and paternal deletions of IGF2 enhancers have been detected in four SRS
      patients. However, no paternal deletions of ICR1 have ever been associated with
      hypomethylation of the IGF2/H19 domain in SRS. We screened for new genetic
      defects within the ICR1 in a cohort of 234 SRS patients with hypomethylated
      IGF2/H19 domain. We report deletions close to the boundaries of ICR1 on the
      paternal allele in one familial and two sporadic cases of SRS with ICR1
      hypomethylation. These deletions are associated with hypomethylation of the
      remaining CBS, and decreased IGF2 expression. These results suggest that these
      regions are most likely required to maintain methylation after fertilization. We
      estimate these anomalies to occur in about 1% of SRS cases with ICR1
      hypomethylation.

PMID- 27701795
TI  - Adequacy of palliative care in a single tertiary neonatal unit.
AB  - AIM: End-of-life care remains part of the scope of practice in all neonatal
      units. This study aimed to characterise the end-of-life care provided in an
      Australian tertiary neonatal centre, where paediatric palliative care was
      accessible via a consultative service. METHODS: This retrospective cohort study
      examined indicators of quality palliative care provided to 46 infants born within
      a 30-month period. The cohort included four infants who received palliative care
      consultations additional to usual neonatal care. The care provided was
      characterised using descriptive statistics. RESULTS: The most common causes of
      death were congenital abnormality (37%) and complications of extreme prematurity
      (22%). Very high proportions of infants and families had family meetings (100%),
      social worker involvement (100%), memory-making opportunities (100%) and
      discussion of autopsy (91%). Opiates were prescribed to 76% in the last day of
      life; most (89%) were administered intravenously. For those prescribed opiates,
      the median parenteral morphine daily equivalent was 290 mcg/kg/day (interquartile
      range = 317) in the last 24 h of life. Antenatal resuscitation planning for
      families of a fetus with a prenatal diagnosis (9%), discussion of preferred
      location of death (9%), verbal communication with general practitioners (15%) and
      access to specialised bereavement care (3%) were infrequently provided.
      CONCLUSIONS: At the time of this study, the neonatal unit was not meeting all of
      the end-of-life care needs of infants and their families. Care was generally more
      comprehensive when the palliative care service was consulted.

PMID- 27701794
TI  - GABAergic hyperinnervation of dentate granule cells in the Ts65Dn mouse model of
      down syndrome: Exploring the role of App.
AB  - It has been suggested that increased GABAergic innervation in the hippocampus
      plays a significant role in cognitive dysfunction in Down syndrome (DS).
      Bolstering this notion, are studies linking hyper-innervation of the dentate
      gyrus (DG) by GABAergic terminals to failure in LTP induction in the Ts65Dn mouse
      model of DS. Here, we used extensive morphometrical methods to assess the status
      of GABAergic interneurons in the DG of young and old Ts65Dn mice and their 2N
      controls. We detected an age-dependent increase in GABAergic innervation of
      dentate granule cells (DGCs) in Ts65Dn mice. The primary source of GABAergic
      terminals to DGCs somata is basket cells (BCs). For this reason, we assessed the
      status of these cells and found a significant increase in the number of BCs in
      Ts65Dn mice compared with controls. Then we aimed to identify the gene/s whose
      overexpression could be linked to increased number of BCs in Ts65Dn and found
      that deleting the third copy of App gene in Ts65Dn mice led to normalization of
      the number of BCs in these mice. Our data suggest that App overexpression plays a
      major role in the pathophysiology of GABAergic hyperinnervation of the DG in
      Ts65Dn mice. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701796
TI  - Persistence of impulsivity in pediatric and adolescent patients with obsessive
      compulsive disorder.
AB  - AIM: Increasing clinical evidence points to impulsivity as a symptom of obsessive
      compulsive disorder (OCD). However, little is known about its persistence over
      time. METHODS: In this study, we evaluated the performance of 12 pediatric
      patients with OCD on the Stroop color-word task, which assesses impulsivity, and
      compared this with age- and sex-matched controls. In parallel, we measured
      changes in hemodynamic responses during the task, using near-infrared
      spectroscopy. As patients in the OCD group were naive to treatment, we compared
      results before and after 3-year medication with serotonin reuptake inhibitors.
      RESULTS: We report that, compared with controls, the OCD group had significantly
      poorer performance and less activation in the prefrontal cortex during the Stroop
      color-word task. Surprisingly, while serotonin-reuptake-inhibitors treatment
      reduced OCD symptomology, it did not improve the diminished hemodynamic responses
      or task performance of these patients. CONCLUSION: Our findings suggest that a
      persistent deficit exists in the inhibitory control of pediatric patients with
      OCD; they also provide insight into the pathophysiology of OCD.

PMID- 27701797
TI  - Opposite in vivo effects of agents that stimulate or inhibit the
      glutamate/cysteine exchanger system xc- on the inhibition of hippocampal LTP by
      Abeta.
AB  - Aggregated amyloid beta-protein (Abeta) is pathognomonic of Alzheimer's disease
      and certain assemblies of Abeta are synaptotoxic. Excess glutamate or diminished
      glutathione reserve are both implicated in mediating or modulating Abeta-induced
      disruption of synaptic plasticity. The system xc- antiporter promotes Na+ 
      independent exchange of cystine with glutamate thereby providing a major source
      of extracellular glutamate and intracellular glutathione concentrations. Here we
      probed the ability of two drugs with opposite effects on system xc-, the
      inhibitor sulfasalazine and facilitator N-acetylcysteine, to modulate the ability
      of Abeta1-42 to inhibit long-term potentiation (LTP) in the CA1 area of the
      anaesthetized rat. Whereas acute systemic treatment with sulfasalazine lowered
      the threshold for Abeta to interfere with synaptic plasticity, N-acetylcysteine
      prevented the inhibition of LTP by Abeta alone or in combination with
      sulfasalazine. Moreover acute N-acetylcysteine also prevented the inhibition of
      LTP by TNFalpha, a putative mediator of Abeta actions, and repeated systemic N
      acetylcysteine treatment for 7 days reversed the delayed deleterious effect of
      Abeta on LTP. Since both of these drugs are widely used clinically, further
      evaluation of their potential beneficial and deleterious actions in early
      Alzheimer's disease seems warranted. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701799
TI  - Editorial Comment from Dr Stranne and Psychotherapist Stranne to Postoperative
      urinary incontinence exacerbates nocturia-specific quality of life after robot
      assisted radical prostatectomy.

PMID- 27701800
TI  - Editorial Comment to Comparison of the morbidity and mortality of cystectomy and
      ileal conduit urinary diversion for neurogenic lower urinary tract dysfunction
      according to the approach: Laparotomy, laparoscopy or robotic.

PMID- 27701801
TI  - Aromatic Osmacyclopropenefuran Bicycles and Their Relevance for the Metal
      Mediated Hydration of Functionalized Allenes.
AB  - The aromatic osmacyclopropenefuran bicycles [OsTp{kappa3 -C1 ,C2 ,O-(C1 H2 C2
      CHC(OEt)O)}(Pi Pr3 )]BF4 (Tp=hydridotris(1-pyrazolyl)borate) and [OsH{kappa3 -C1
      ,C2 ,O-(C1 H2 C2 CHC(OEt)O)}(CO)(Pi Pr3 )2 ]BF4 , with the metal fragment in a
      common vertex between the fused three- and five-membered rings, have been
      prepared via the pi-allene intermediates [OsTp(eta2 -CH2 =CCHCO2 Et)(OCMe2 )(Pi
      Pr3 )]BF4 and [OsH(eta2 -CH2 =CCHCO2 Et)(CO)(OH2 )(Pi Pr3 )2 ]BF4 , and their
      aromaticity analyzed by DFT calculations. The bicycle containing the [OsH(CO)(Pi
      Pr3 )2 ]+ metal fragment is a key intermediate in the [OsH(CO)(OH2 )2 (Pi Pr3 )2
      ]BF4 -catalyzed regioselective anti-Markovnikov hydration of ethyl buta-2,3
      dienoate to ethyl 4-hydroxycrotonate.

PMID- 27701802
TI  - Molecularly Designed Stabilized Asymmetric Hollow Fiber Membranes for Aggressive
      Natural Gas Separation.
AB  - New rigid polyimides with bulky CF3 groups were synthesized and engineered into
      high-performance hollow fiber membranes. The enhanced rotational barrier provided
      by properly positioned CF3 side groups prohibited fiber transition layer collapse
      during cross-linking, thereby greatly improving CO2 /CH4 separation performance
      compared to conventional materials for aggressive natural gas feeds.

PMID- 27701803
TI  - Eligibility criteria for therapeutic hypothermia: From trials to clinical
      practice.
AB  - AIM: Whole body therapeutic hypothermia (TH) for hypoxic ischaemic encephalopathy
      was introduced into clinical practice in New South Wales (NSW) and Australian
      Capital Territory in 2007. State-wide policy adopting the eligibility criteria
      and practice based on trial-designs was published in 2009. METHODS: The study was
      conducted by retrospectively reviewing medical records of all TH infants born
      between 2007 and 2011 in NSW and Australian Capital Territory to examine if
      eligibility criteria (assessed against evidence-based policy directives) were
      met. RESULTS: A total of 207 infants received TH, 104 (50%) did not meet the
      eligibility criteria defined in NSW policy directive. Over the 5-year period, the
      proportion of infants meeting the eligibility criteria did not change. Seventy
      percent of infants (73 out of 104) not meeting eligibility criteria did not
      fulfil the criteria for 'evidence of asphyxia', although half of them met
      'moderate or severe encephalopathy criterion'. Adverse events (hypotension,
      coagulopathy and arrhythmia), were more common in the 'criteria met' group than
      the 'criteria not met' group (89 vs. 71%, P = 0.001). Similar proportions of
      infants had TH discontinued before 72 h (criteria met: 32 (31%) vs. criteria not
      met: 27(26%)). Most frequent reason for early cessation was 'palliation' (19/32,
      59%) in criteria met and 'clinical improvement' (16/27, 59%) in criteria not met
      group. CONCLUSIONS: Many TH infants were treated based on clinician judgement,
      though not meeting the trial-design policy criteria. Early TH cessation (<72 h)
      was common. Future studies are warranted on long-term neurodevelopmental outcomes
      for all infants receiving TH particularly those with early cessation of therapy.

PMID- 27701804
TI  - Deactivation of Mcl-1 by Dual-Function Small-Molecule Inhibitors Targeting the
      Bcl-2 Homology 3 Domain and Facilitating Mcl-1 Ubiquitination.
AB  - By means of limited proteolysis assay, three-dimensional NMR, X-ray
      crystallography and alanine mutations, a dynamic region at the Q221R222N223 motif
      in the Bcl-2 homology 3 (BH3) domain of Mcl-1 has been identified as a
      conformational switch which controls Mcl-1 ubiquitination. NoxaBH3 binding biases
      the QRN motif toward a helical conformation, thus leading to an enhanced in vitro
      ubiquitination of Mcl-1. In contrast, BimBH3 binding biases the QRN motif toward
      a nonhelical conformation, thus leading to the inhibition of ubiquitination. A
      dual function Mcl-1 inhibitor, which locates at the BH3 domain of Mcl-1 and forms
      hydrogen bond with His224 to drive a helical QRN conformation, so that it not
      only interferes with the pro-apoptotic partners, but also facilitates Mcl-1
      ubiquitination in living cells, is described. As a result, this inhibitor
      manifests a more effective apoptosis induction in Mcl-1-dependent cancer cells
      than other inhibitors exhibiting a similar binding affinity with it.

PMID- 27701805
TI  - Recent Developments in Coinage Metal Catalyzed Transformations of Stabilized
      Vinyldiazo Compounds: Beyond Carbenic Pathways.
AB  - Transition metal-catalyzed transformations of vinyldiazo compounds have become a
      versatile tool in organic synthesis. Although several transition metals have been
      investigated for this purpose, this field has been mainly dominated by dirhodium
      catalysts. Remarkable levels of chemo-, regio-, diastereo- and enantioselectivity
      have been reached in some of these rhodium-catalyzed transformations. In the last
      few years coinage metals have also emerged as useful catalysts in transformations
      involving vinyldiazo compounds. In some cases, highly efficient catalyst
      dependent protocols arising from divergent mechanistic pathways have been
      reported. In this Personal Account, we aim to showcase recent advances in metal
      coinage catalyzed transformations of vinyldiazoacetates, an exciting field of
      research to which our group has actively contributed in the last few years.

PMID- 27701806
TI  - Photosensitizing Electron Transfer Processes of Fullerenes, Carbon Nanotubes, and
      Carbon Nanohorns.
AB  - In this account, studies on the photosensitizing electron transfer of
      nanocarbons, such as fullerenes, single-walled carbon nanotubes (SWCNTs), and
      carbon nanohorns (CNH), performed in our laboratory for about 15 years in the
      early 21st century have been briefly reviewed. These novel nanocarbons act as
      excellent electron acceptors, when they are linked to light-absorbing electron
      donors, such as porphyrins or phthalocyanines. For such molecule-nanocarbon
      hybrids, the direct confirmation of fast, transient, electron-transfer phenomena
      must be performed with time-resolved spectroscopic methods, such as transient
      absorption spectral measurements, in addition to fluorescence time-profile
      measurements in the wide-wavelength regions. Careful use of these methods affords
      useful information to understand photoinduced electron-transfer mechanisms. In
      addition, kinetic data obtained by these methods can assist in the construction
      of light-active devices, such as photovoltaic cells and solar H2 -generation
      systems.

PMID- 27701807
TI  - Lewis Base Catalyzed Stereo- and Regioselective Bromocyclization.
AB  - Oxygen- and nitrogen-containing heterocyclic compounds are widely recognized as
      key components in many natural products and biologically relevant molecules, but
      often the problem comes down to methodologies in synthesizing them.
      Halocyclization of olefinic substrates is a promising strategy in the
      construction of O- and N-heterocyclic compounds, which further signifies the
      development of their asymmetric variants. Over the past years, our group has been
      devoted to this particular area of asymmetric electrophilic halocyclization with
      chalcogen-containing molecules as catalysts. In this account, the main focus is
      on the development of our novel chiral catalysts and applications derived from
      the reaction products.

PMID- 27701808
TI  - Synthesis of Pyrrolidines and Pyrrolizidines with alpha-Pseudoquaternary Centers
      by Copper-Catalyzed Condensation of alpha-Diazodicarbonyl Compounds and Aryl
      gamma-Lactams.
AB  - N-aryl gamma-lactams react intermolecularly with acceptor-acceptor diazo
      reagents, usually dicarbonyl compounds, in a copper-catalyzed process to yield
      functionalized pyrrolidines with alpha-pseudoquaternary centers. As 1,2-acyl or 
      phosphoryl migration is preferred, single regioisomers are obtained. Furthermore,
      in the presence of a Lewis acid, subsequent Friedel-Crafts reactions yield
      tricyclic pyrrolizidines in excellent yields (90-96 %) and diastereoselectivities
      (up to >20:1).

PMID- 27701809
TI  - Bioactive and inert dental glass-ceramics.
AB  - The global market for dental materials is predicted to exceed 10 billion dollars
      by 2020. The main drivers for this growth are easing the workflow of dentists and
      increasing the comfort of patients. Therefore, remarkable research projects have
      been conducted and are currently underway to develop improved or new dental
      materials with enhanced properties or that can be processed using advanced
      technologies, such as CAD/CAM or 3D printing. Among these materials, zirconia,
      glass or polymer-infiltrated ceramics, and glass-ceramics (GCs) are of great
      importance. Dental glass-ceramics are highly attractive because they are easy to
      process and have outstanding esthetics, translucency, low thermal conductivity,
      high strength, chemical durability, biocompatibility, wear resistance, and
      hardness similar to that of natural teeth, and, in certain cases, these materials
      are bioactive. In this review article, we divide dental GCs into the following
      two groups: restorative and bioactive. Most restorative dental glass-ceramics
      (RDGCs) are inert and biocompatible and are used in the restoration and
      reconstruction of teeth. Bioactive dental glass-ceramics (BDGCs) display bone
      bonding ability and stimulate positive biological reactions at the
      material/tissue interface. BDGCs are suggested for dentin hypersensitivity
      treatment, implant coating, bone regeneration and periodontal therapy. Throughout
      this paper, we elaborate on the history, processing, properties and applications
      of RDGCs and BDGCs. We also report on selected papers that address promising
      types of dental glass-ceramics. Finally, we include trends and guidance on
      relevant open issues and research possibilities. (c) 2016 Wiley Periodicals, Inc.
      J Biomed Mater Res Part A: 105A: 619-639, 2017.

PMID- 27701810
TI  - Glassworts as Possible Anticancer Agents Against Human Colorectal Adenocarcinoma
      Cells with Their Nutritive, Antioxidant and Phytochemical Profiles.
AB  - In this study, the possible uses of glassworts as potential food ingredients and
      their antiproliferative activity against colorectal adenocarcinoma cells together
      with their antioxidant and phytochemical profiles were investigated for the first
      time. MeOH extracts of five different taxa collected from different localities
      were screened for their antioxidant capacities by DPPH (IC50 2.91 - 5.49 mg/ml)
      and ABTS (24.4 - 38.5 MUmol TE/g extract) assays. Salicornia freitagii exhibited
      the highest DPPH radical scavenging activity. LC/MS/MS analysis displayed that
      vanillic acid and p-coumaric acid were two main phenolic compounds in the
      extract. Salicornia freitagii extracts also exhibited high antiproliferative
      activity against HT-29 (IC50 1.67 mg/ml) and Caco-2 (IC50 3.03 mg/ml) cells for
      72 h. Mineral analysis indicated that all the species with different proportions
      of elemental components contained high amount of cations. These results indicate
      that investigated glassworts, with their high phenolic and mineral contents and
      also notable antioxidant and cytotoxic properties, may be utilized as a promising
      source of therapeutics.

PMID- 27701811
TI  - Grandparents: A hardly recognized part of the childhood cancer family.

PMID- 27701812
TI  - 9-Silafluorenyl Dichlorides as Chemically Ligating Coupling Agents and Their
      Application in Peptide Synthesis.
AB  - A fundamentally simple, mild, and practical procedure for peptide bond formation
      is reported that employs a stoichiometric amount of easy-to-access 9
      silafluorenyl dichlorides as the coupling agent. Without initial preactivation or
      elaboration of the carboxylic acid or amine termini of the amino acids, the
      developed reagent is proposed to act through an unprecedented chemical ligation
      mechanism, bringing the two coupling partners together before being subsequently
      eliminated. The desired amides or peptide bonds are thus furnished in good yields
      and with low to no epimerization.

PMID- 27701813
TI  - Variations in Essential Oil Compositions of Lavandula pubescens (Lamiaceae)
      Aerial Parts Growing Wild in Yemen.
AB  - Lavandula pubescens Decne. is one of five Lavandula species growing wild in
      Yemen. The plant is used in Yemeni traditional medicine, and the essential oil
      tends to be rich in carvacrol. In this work, L. pubescens was collected from
      eight different locations in Yemen, the essential oils obtained by
      hydrodistillation, and the oils analyzed by gas chromatography/mass spectrometry
      (GC/MS). Principal component analysis (PCA) and hierarchical cluster analysis
      (HCA) were used to differentiate between the L. pubescens samples. The essential
      oils were rich in carvacrol (60.9 - 77.5%), with lesser concentrations of
      carvacrol methyl ether (4.0 - 11.4%), caryophyllene oxide (2.1 - 6.9%), and
      terpinolene (0.6 - 9.2%). The essential oil compositions in this study showed
      very high similarity, but it was possible to discern two separate groups based on
      minor components, in particular the concentrations of terpinolene, carvacrol
      methyl ether, m-cymen-8-ol, and caryophyllene oxide.

PMID- 27701814
TI  - A silicone fiber coating as approach for the reduction of fibroblast growth on
      implant electrodes.
AB  - In cochlear implant (CI) patients, an increase in electrode impedance due to
      fibrotic encapsulation is frequently observed. Several attempts have been
      proposed to reduce fibroblast growth at the electrode contacts, but none proved
      to be satisfactory so far. Here, a silicone fiber coating of the electrode
      contacts is presented that provides a complex micro-scale surface topography and
      increases hydrophobicity to inhibit fibroblast growth and adhesion. A silicone
      fiber electrospinning process was developed to create a thin and porous fiber
      mesh. Fiber coatings were applied on graphite specimen holders, glass cover slips
      and CI electrode contacts. For characterization of the coating's pore
      distribution, water contact angle and electrical impedance were analyzed.
      Cytotoxicity and in vitro fibroblast growth were evaluated to assess biological
      efficacy of the coatings. It could be shown that the silicone fiber mesh itself
      had only minor influence on electrode impedance. A uniform, hydrophobic fiber
      coating could be achieved that decreased fibroblast growth without showing toxic
      effects. Finally, CI electrode contacts were successfully coated in order to
      present this promising approach for a long-term improvement of CI electrodes. We
      are one of the first groups that could successfully adapt the electrospinning
      technique on the utilization of silicone. Silicone was chosen because of its high
      hydrophobicity, chemical stability and excellent biocompatibility and as it is
      one of the biomaterials already used in CIs. (c) 2016 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 105B: 2574-2580, 2017.

PMID- 27701815
TI  - 3D Structure Determination of an Unstable Transient Enzyme Intermediate by
      Paramagnetic NMR Spectroscopy.
AB  - Enzyme catalysis relies on conformational plasticity, but structural information
      on transient intermediates is difficult to obtain. We show that the three
      dimensional (3D) structure of an unstable, low-abundance enzymatic intermediate
      can be determined by nuclear magnetic resonance (NMR) spectroscopy. The approach
      is demonstrated for Staphylococcus aureus sortase A (SrtA), which is an
      established drug target and biotechnological reagent. SrtA is a transpeptidase
      that converts an amide bond of a substrate peptide into a thioester. By measuring
      pseudocontact shifts (PCSs) generated by a site-specific cysteine-reactive
      paramagnetic tag that does not react with the active-site residue Cys184, a
      sufficient number of restraints were collected to determine the 3D structure of
      the unstable thioester intermediate of SrtA that is present only as a minor
      species under non-equilibrium conditions. The 3D structure reveals structural
      changes that protect the thioester intermediate against hydrolysis.

PMID- 27701816
TI  - Morita-Baylis-Hillman (MBH) Reaction Derived Nitroallylic Alcohols, Acetates and
      Amines as Synthons in Organocatalysis and Heterocycle Synthesis.
AB  - The Morita-Baylis-Hillman (MBH) reaction is one of the most useful and efficient
      protocols for constructing new carbon-carbon bonds between an activated olefin
      and electrophiles in the presence of a tertiary amine/phosphine. Herein, we
      present the use of MBH alcohols, which are obtained from the reaction of
      nitrostyrenes with aldehydes, as well as acetates and amines derived thereof in
      several organocatalytic transformations. Densely functionalised MBH adducts can
      also be used to synthesise substituted heteroaromatic compounds, such as furan,
      pyrrole, pyrazole and imidazole derivatives.

PMID- 27701817
TI  - The Origin of Improved Electrical Double-Layer Capacitance by Inclusion of
      Topological Defects and Dopants in Graphene for Supercapacitors.
AB  - Low-energy density has long been the major limitation to the application of
      supercapacitors. Introducing topological defects and dopants in carbon-based
      electrodes in a supercapacitor improves the performance by maximizing the
      gravimetric capacitance per mass of the electrode. However, the main mechanisms
      governing this capacitance improvement are still unclear. We fabricated planar
      electrodes from CVD-derived single-layer graphene with deliberately introduced
      topological defects and nitrogen dopants in controlled concentrations and of
      known configurations, to estimate the influence of these defects on the
      electrical double-layer (EDL) capacitance. Our experimental study and theoretical
      calculations show that the increase in EDL capacitance due to either the
      topological defects or the nitrogen dopants has the same origin, yet these two
      factors improve the EDL capacitance in different ways. Our work provides a better
      understanding of the correlation between the atomic-scale structure and the EDL
      capacitance and presents a new strategy for the development of experimental and
      theoretical models for understanding the EDL capacitance of carbon electrodes.

PMID- 27701818
TI  - Molecular Imaging of Growth, Metabolism, and Antibiotic Inhibition in Bacterial
      Colonies by Laser Ablation Electrospray Ionization Mass Spectrometry.
AB  - Metabolism in microbial colonies responds to competing species, rapidly evolving
      genetic makeup, and sometimes dramatic environmental changes. Conventional
      characterization of the existing and emerging microbial strains and their
      interactions with antimicrobial agents, e.g., the Kirby-Bauer susceptibility
      test, relies on time consuming methods with limited ability to discern the
      molecular mechanism and the minimum inhibitory concentration. Assessing the
      metabolic adaptation of microbial colonies requires their non-targeted molecular
      imaging in a native environment. Laser ablation electrospray ionization (LAESI)
      is an ambient ionization technique that in combination with mass spectrometry
      (MS) enables the analysis and imaging of numerous metabolites and lipids. In this
      contribution, we report on the application of LAESI-MS imaging to gain deeper
      molecular insight into microbe-antibiotic interactions, and enhance the
      quantitative nature of antibiotic susceptibility testing while significantly
      reducing the required incubation time.

PMID- 27701819
TI  - A Two-Step Method for Transferring Single-Walled Carbon Nanotubes onto a Hydrogel
      Substrate.
AB  - Carbon nanotube (CNT)-hydrogel nanocomposites are beneficial for various
      biomedical applications, such as nerve regeneration, tissue engineering, sensing,
      or implant coatings. Still, there are impediments to developing nanocomposites,
      including attaining a homogeneous CNT-polymer dispersion or patterning CNTs on
      hydrogels. While few approaches have been reported for patterning CNTs on
      polymeric substrates, these methods include high temperature, high vacuum or
      utilize a sacrificial layer and, hence, are incompatible with hydrogels as they
      lead to irreversible collapse in hydrogel structure. In this study, a novel two
      step method is designed to transfer CNTs onto hydrogels. First, dense CNTs are
      grown on quartz substrates. Subsequently, hydrogel solutions are deposited on the
      quartz-grown CNTs. Upon gelation, the hydrogel with transferred CNTs is peeled
      from the quartz. Successful transfer is confirmed by scanning electron microscopy
      and indirectly by cell attachment. The efficient transfer is attributed to pi
      interactions pregelation between the polymers in solution and the CNTs.

PMID- 27701820
TI  - Detection of intermolecular transferred NOEs in large protein complexes using
      asymmetric deuteration: HIV-1 gp120 in complex with a CCR5 peptide.
AB  - Weak protein-protein and protein-ligand interactions play important roles in
      biological recognition. In many cases, simplification of structural studies of
      large protein complexes is achieved by investigation of the interaction between
      the protein and a weakly binding segment of its protein ligand. Detection of
      pairwise interactions in such complexes is a major challenge for both X-ray
      crystallography and nuclear magnetic resonance. We demonstrate that transferred
      nuclear Overhauser effect (TRNOE), in combination with asymmetric deuteration of
      a protein and a peptide ligand can be used to detect intermolecular interactions
      in large protein complexes with molecular weights up to ~ 100 kDa. Using this
      approach, we revealed interactions between tyrosine residues of a 27-residue
      peptide (deuterated at Ile and Val residues) corresponding to the N-terminal
      segment of the human C-C chemokine receptor 5 (CCR5) chemokine receptor, and a 43
      kDa construct of gp120 envelope protein of human immunodeficiency virus type 1
      (deuterated on all aromatics) complexed with a cluster of differentiation 4-mimic
      miniprotein. The complex was present mostly as a dimer as determined by T2
      relaxation measurements. The TRNOE crosspeaks in the ternary complex were
      assigned to the specific Tyr protons in the CCR5 peptide and to methyl protons,
      predominantly of isoleucine residues, and also of leucine and/or valine residues
      of gp120. The TRNOE/asymmetric deuteration method benefits from the sensitivity
      of the homonuclear NOESY experiment and does not suffer the sensitivity losses
      associated with isotope-edited/isotope-filtered approaches that rely on
      magnetization transfer between protons and heteronuclei that are bonded to them.
      The technique can be widely applied for studying large protein complexes that
      exhibit fast off-rates.

PMID- 27701821
TI  - Diffusion-weighted magnetic resonance imaging for residual and recurrent
      cholesteatoma: a systematic review and meta-analysis.
AB  - BACKGROUND: Diagnosis and management of recurrent or residual cholesteatoma can
      be problematic. Diffusion-weighted imaging magnetic resonance imaging (MRI)
      sequences have been used for follow-up of such lesions. More recent non
      echoplanar imaging (non-EPI) sequences are thought to be superior to older
      echoplanar imaging (EPI) sequences. OBJECTIVE OF REVIEW: Evaluate whether
      diffusion-weighted magnetic resonance imaging is useful in the diagnosis of
      recurrent or residual cholesteatoma. TYPE OF REVIEW: Systematic review and meta
      analysis. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, Web of Science and the
      Cochrane Database were searched, with no limits on date or language. STUDY
      SELECTION: Adults or children who had previously undergone tympanomastoid surgery
      by any method with confirmation of recurrence/residual disease by second
      look/revision surgery. EVALUATION METHODS: Two reviewers independently reviewed
      studies. Data extracted on 11 domains and rechecked. DATA SYNTHESIS: Statistical
      analysis with SPSS. RESULTS: A total of 575 studies were identified of which 27
      met the inclusion criteria. These covered 727 patient episodes. For EPI studies:
      sensitivity (sd) 71.82 (24.5), specificity (sd) 89.36 (13.4), PPV (sd) 93.36
      (8.1) and NPV (sd) 73.36 (15.8). For non-EPI studies: sensitivity 89.79 (12.1),
      specificity (sd) 94.57 (5.8), PPV (sd) 96.50 (4.2) and NPV 80.46 (20.2). Improved
      sensitivity of non-EPI sequences reached significance (P = 0.02). CONCLUSIONS:
      Diffusion-weighted MRI is both sensitive and specific for the detection of
      recurrent or residual cholesteatoma following ear surgery. Non-EPI techniques are
      superior to EPI techniques.

PMID- 27701822
TI  - Long-term outcome for kaposiform hemangioendothelioma: A report of two cases.
AB  - Kaposiform hemangioendothelioma (KHE) is a rare aggressive vascular tumor of skin
      and deep soft tissues that typically presents in infancy and may be associated
      with a potentially life-threatening coagulopathy known as Kasabach-Merrit
      phenomenon (KMP). Recent advances in medical therapy have successfully treated
      many patients. However, our knowledge regarding the natural history of these
      lesions and optimum surveillance strategies remains rudimentary. We report two
      young women who had KHE with KMP treated in infancy and presented in adolescence
      with comorbidities related to their KHE tumor. This presentation supports the
      need for long-term surveillance in these patients.

PMID- 27701823
TI  - Differential proteomic analysis of the metabolic network of the marine sulfate
      reducer Desulfobacterium autotrophicum HRM2.
AB  - The marine sulfate-reducing bacterium Desulfobacterium autotrophicum HRM2 belongs
      to the deltaproteobacterial family Desulfobacteraceae and stands out for its
      capacity of facultative chemolithoautotrophic growth (next to heterotrophy).
      Here, proteomics-driven metabolic reconstruction was based on a combination of 2D
      DIGE, shotgun proteomics, and analysis of the membrane protein enriched fraction
      applied to eight different substrate adaptation conditions (seven aliphatic
      compounds plus H2 /CO2 ). In total, 1344 different proteins were identified (~27%
      of the 4947 genome-predicted), from which a complex metabolic network was
      reconstructed consisting of 136 proteins (124 detected; ~91%). Peripheral
      degradation routes for organic substrates feed directly or via the methylmalonyl
      CoA pathway into the Wood-Ljungdahl pathway (WLP) for terminal oxidation to CO2 .
      Chemolithoautotrophic growth apparently involves the periplasmic [Ni/Fe/Se]
      containing hydrogenase HysAB (H2 oxidation), the reductively operating WLP (CO2
      fixation), and classical gluconeogenesis. Diverse soluble proteins (e.g., Hdr,
      Etf) probably establish a fine balanced cytoplasmic electron transfer network
      connecting individual catabolic reactions with the membrane menaquinone pool. In
      addition, multiple membrane protein complexes (Nqr, Qmo, Qrc, Rnf1, Rnf2, and
      Tmc) provide ample routes for interacting with the reducing equivalent pool and
      delivering electrons to dissimilatory sulfate reduction (both localized in the
      cytoplasm). Overall, this study contributes to the molecular understanding of the
      habitat-relevant Desulfobacteraceae.

PMID- 27701824
TI  - New horizons in geomycology.

PMID- 27701825
TI  - Engineering Protein Self-Assembly: A New Approach for the Design of Octahedral
      Cages.
AB  - A new symmetry-based approach allowed the self-assembly of an octahedral protein
      nanostructure. C3 trimeric and C4 tetrameric oligomerization domains can be
      combined in an engineered protein to direct assembly into a desired object. This
      work might provide the basis for a more general and flexible strategy to control
      protein self-assembly.

PMID- 27701826
TI  - In Vitro Topographical Model of Fuchs Dystrophy for Evaluation of Corneal
      Endothelial Cell Monolayer Formation.
AB  - A common indication for corneal transplantation, which is the most transplanted
      tissue, is a dysfunctional corneal endothelium due to Fuchs' endothelial
      dystrophy (FED). FED is diagnosed by the presence of in vivo pathological
      microtopography on the Descemet membrane, which is called corneal guttata.
      Minimally invasive corneal endothelial cell regenerative procedures such as
      endothelial cell injection therapy and Rho kinase inhibitor pharmacotherapy have
      been proposed as alternatives to conventional corneal transplantation for FED
      patients. However, the effect of guttata on monolayer reformation following such
      therapies is unknown and there is no equivalent in vitro or animal model to study
      monolayer reformation. Using a synthetic guttata FED disease model, the formation
      of the monolayer is investigated to evaluate the efficacy of both therapies.
      Results obtained suggest that guttata dimensions, density, and spacing greatly
      affect the fate of corneal endothelial cells in terms of migratory behavior and
      monolayer reformation. Densely packed synthetic guttata mimicking late-stage FED
      hinders monolayer reformation, while synthetic guttata of lower height and
      density show improved monolayer formation. These results suggest that severity of
      the FED, as determined by height and density of existing guttata, can potentially
      attenuate corneal endothelial monolayer formation of corneal cell injection
      therapy and pharmacotherapy.

PMID- 27701828
TI  - Promoting the Synthesis of Methanol: Understanding the Requirements for an
      Industrial Catalyst for the Conversion of CO2.
AB  - The hydrogenation of CO2 to methanol is a potential process for the sustainable
      production of synthetic liquid fuels. The Cu/ZnO catalyst employed for this
      reaction has been studied extensively for many years, and recent progress now has
      the potential to turn it into a prototype for complex promotional interactions in
      heterogeneous catalysis.

PMID- 27701827
TI  - Beneficial Effects of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a
      Mouse Model of Autism and in a Case Report of Autism.
AB  - AIMS: Autism spectrum disorder (ASD) is a condition defined by social
      communication deficits and repetitive restrictive behaviors. Association of the
      fatty acid amide palmitoylethanolamide (PEA) with the flavonoid luteolin displays
      neuroprotective and antiinflammatory actions in different models of central
      nervous system pathologies. We hypothesized that association of PEA with luteolin
      might have therapeutic utility in ASD, and we employed a well-recognized autism
      animal model, namely sodium valproate administration, to evaluate cognitive and
      motor deficits. METHODS: Two sets of experiments were conducted. In the first, we
      investigated the effect of association of ultramicronized PEA with luteolin, co
      ultramicronized PEA-LUT(r) (co-ultraPEA-LUT(r)) in a murine model of autistic
      behaviors, while in the second, the effect of co-ultraPEA-LUT(r) in a patient
      affected by ASD was examined. RESULTS: Co-ultraPEA-LUT(r) treatment ameliorated
      social and nonsocial behaviors in valproic acid-induced autistic mice and
      improved clinical picture with reduction in stereotypes in a 10-year-old male
      child. CONCLUSION: These data suggest that ASD symptomatology may be improved by
      agents documented to control activation of mast cells and microglia. Co-ultraPEA
      LUT(r) might be a valid and safe therapy for the symptoms of ASD alone or in
      combination with other used drugs.

PMID- 27701829
TI  - The VHOT (Vindaloo Hastens Outpouring of Troponins) Study.
AB  - BACKGROUND: Multiple cardiac and non-cardiac processes may cause an elevated
      highly sensitive troponin (hsTn). We postulated that the consumption of a
      seriously hot vindaloo could cause an increase in hsTn levels in seemingly
      healthy volunteers. OBJECTIVE: To determine whether eating a very hot curry can
      cause elevated hsTn. METHODS: This was a prospective observational cohort study.
      Participants had blood drawn for hsTn pre-ingestion and at 2 and 4 h post
      ingestion of, first, a rather mild butter chicken and, 2 weeks later, a seriously
      hot lamb vindaloo. We assessed pre-curry tolerance and perception of curry
      hotness for both curries using the VHOT scale. RESULTS: Although no participant
      had a troponin above the reference range at any point in time, we found dramatic
      relative increases in troponin in many of our participants. In the vindaloo
      phase, 8/22 (36%) had a relative change >20%, whereas 5/22 (23%) had a relative
      change >50% at 4 h. However, these changes were not significantly different to
      those in the butter chicken phase. Based on biological variability alone, 15/22
      (68%) had a relative change of >20%, and 11/22 (50%) had a relative change of
      >50% between the two sessions (pre-ingestion). CONCLUSIONS: Eating a seriously
      hot vindaloo does not appear to be a risk factor for troponitis, and people may
      consume vindaloo safely with the knowledge that this is unlikely to result in
      significant damage to their myocardium. However, clinicians should be aware of
      the biological variability of hsTn and exercise caution when interpreting
      apparent changes within the normal range.

PMID- 27701830
TI  - Growth of magnetotactic sulfate-reducing bacteria in oxygen concentration
      gradient medium.
AB  - Although dissimilatory sulfate-reducing bacteria (SRB) are generally described as
      strictly anaerobic organisms with regard to growth, several reports have shown
      that some SRB, particularly Desulfovibrio species, are quite resistant to O2 .
      For example, SRB remain viable in many aerobic environments while some even
      reduce O2 to H2 O. However, reproducible aerobic growth of SRB has not been
      unequivocally documented. Desulfovibrio magneticus is a SRB that is also a
      magnetotactic bacterium (MTB). MTB biomineralize magnetosomes which are
      intracellular, membrane-bounded, magnetic iron mineral crystals. The ability of
      D. magneticus to grow aerobically in several different media under air where an
      O2 concentration gradient formed, or under O2 -free N2 gas was tested. Under air,
      cells grew as a microaerophilic band of cells at the oxic-anoxic interface in
      media lacking sulfate. These results show that D. magneticus is capable of
      aerobic growth with O2 as a terminal electron acceptor. This is the first report
      of consistent, reproducible aerobic growth of SRB. This finding is critical in
      determining important ecological roles SRB play in the environment.
      Interestingly, the crystal structure of the magnetite crystals of D. magneticus
      grown under microaerobic conditions showed significant differences compared with
      those produced anaerobically providing more evidence that environmental
      parameters influence magnetosome formation.

PMID- 27701831
TI  - Clinical outcomes of levalbuterol versus racemic albuterol in pediatric patients
      with asthma: Propensity score matching approach in a medicaid population.
AB  - OBJECTIVE: Racemic albuterol and levalbuterol are used to treat acute episodes of
      asthma. The main objective of this study was to compare levalbuterol therapy to
      albuterol therapy on incidence rates of subsequent emergency department (ED)
      visits and hospitalizations. METHOD: We conducted a retrospective cohort study of
      asthmatic children who had pharmacy refills for levalbuterol/albuterol in the
      South Carolina Medicaid database in 2002-2011. Children receiving levalbuterol
      were matched to those receiving albuterol using propensity score matching
      technique. For ED visits and separately for hospitalizations, multivariable
      negative binomial regression was used to estimate the two group-specific
      incidence rates and the incidence rate ratio (IRR). RESULTS: A total of 8,172
      asthmatic patients aged 2-18 years were identified in the South Carolina Medicaid
      database. During the 12-month follow-up period, the levalbuterol group had fewer
      asthma-related ED visits and hospitalizations: 939 (11.49%) children had asthma
      related ED visits (levalbuterol: 8.76%; albuterol: 14.21%), and 89 (1.09%)
      children had asthma-related hospitalizations (levalbuterol: 1.07%; albuterol:
      1.12%). Comparing the levalbuterol group to the albuterol group, the adjusted IRR
      estimate was 0.57 (95% confidence interval [CI], 0.49-0.65) for of asthma-related
      ED visits, and 0.93 (95%CI, 0.99-1.63) for hospitalizations. Children filling
      levalbuterol also had a lower IRR of all-cause ED visit (0.88; 95%CI, 0.82-0.95),
      but similar IRR of all-cause hospitalizations (1.08; 95%CI, 0.82-1.42).
      CONCLUSION: This observational study of children aged 2-18 demonstrated
      levalbuterol prescription fills were associated with reduced ED visits, but not
      hospitalizations. Additional research may be necessary to assess this
      association. Pediatr Pulmonol. 2017;52:516-523. (c) 2016 Wiley Periodicals, Inc.

PMID- 27701832
TI  - Medicine in small doses.

PMID- 27701833
TI  - Local infiltration analgesia in total knee arthroplasty: why it may not be
      effective in surgical practice.

PMID- 27701835
TI  - Response to Re: Short-term outcomes of local infiltration anaesthetic in total
      knee arthroplasty: a randomized controlled double-blinded controlled trial.

PMID- 27701836
TI  - Re: Short-term outcomes of local infiltration anaesthetic in total knee
      arthroplasty: a randomized controlled double-blinded controlled trial.

PMID- 27701837
TI  - The Generic Surgical Sciences Examination training programme improves
      participant's knowledge and pass rates.

PMID- 27701838
TI  - Two technique modifications for a safer laparoscopic appendicectomy.

PMID- 27701839
TI  - Breast localization techniques and margin definitions used by Australian and New
      Zealand surgeons.

PMID- 27701840
TI  - Long-term outcome after ileal pouch-anal anastomosis for ulcerative colitis.

PMID- 27701841
TI  - Colonic stenting in malignant large bowel obstruction: an unanswered question.

PMID- 27701842
TI  - Re: Local infiltration analgesia in total knee arthroplasty: why it may not be
      effective in surgical practice.

PMID- 27701843
TI  - Expression of the diguanylate cyclase GcbA is regulated by FleQ in response to
      cyclic di-GMP in Pseudomonas putida KT2440.
AB  - Cyclic di-GMP (c-di-GMP), a ubiquitous bacterial second messenger that regulates
      diverse cellular processes, is synthesized by diguanylate cyclase (DGC) and
      degraded by phosphodiesterase (PDE). GcbA is a well conserved DGC among
      Pseudomonas species, and has been reported to influence biofilm formation and
      flagellar motility in Pseudomonas fluorescens and Pseudomonas aeruginosa. Here we
      confirm the function of GcbA in Pseudomonas putida and reveal that expression of
      GcbA is regulated by FleQ in response to c-di-GMP. GcbA deletion impaired initial
      biofilm formation and enhanced swimming motility, but showed no influence on
      biofilm maturation in Pseudomonas putida. Deletion of the c-di-GMP effector FleQ
      led to a significant decrease in transcription of gcbA. Moreover, reducing c-di
      GMP levels promoted gcbA transcription in a FleQ dependent way, while enhancing c
      di-GMP levels abolished the promotion. In in vitro experiments we found that FleQ
      bound to gcbA promoter DNA and the binding was inhibited by c-di-GMP. Besides,
      FleN, an anti-activator of FleQ, and the sigma factor RpoN also participated in
      transcription of gcbA. Our finding expands the complexity of FleQ-dependent
      regulation and reveals a self-regulation function of c-di-GMP by regulating GcbA
      expression via FleQ.

PMID- 27701844
TI  - Generation of accurate peptide retention data for targeted and data independent
      quantitative LC-MS analysis: Chromatographic lessons in proteomics.
AB  - The emergence of data-independent quantitative LC-MS/MS analysis protocols
      further highlights the importance of high-quality reproducible chromatographic
      procedures. Knowing, controlling and being able to predict the effect of multiple
      factors that alter peptide RP-HPLC separation selectivity is critical for
      successful data collection for the construction of ion libraries. Proteomic
      researchers have often regarded RP-HPLC as a "black box", while vast amount of
      research on peptide separation is readily available. In addition to obvious
      parameters, such as the type of ion-pairing modifier, stationary phase and column
      temperature, we describe the "mysterious" effects of gradient slope, column size
      and flow rate on peptide separation selectivity. Retention time variations due to
      these parameters are governed by the linear solvent strength (LSS) theory on a
      peptide level by the value of its slope S in the basic LSS equation-a parameter
      that can be accurately predicted. Thus, the application of shallower gradients,
      higher flow rates, or smaller columns will each increases the relative retention
      of peptides with higher S-values (long species with multiple positively charged
      groups). Simultaneous changes to these parameters that each drive shifts in
      separation selectivity in the same direction should be avoided. The unification
      of terminology represents another pressing issue in this field of applied
      proteomics that should be addressed to facilitate further progress.

PMID- 27701845
TI  - End-of-life issues: Withdrawal and withholding of life-sustaining healthcare in
      the emergency department: A comparison between emergency physicians and emergency
      registrars: A sub-study.
AB  - OBJECTIVE: We investigated and compared the importance of the considerations and
      discussions when withdrawing and withholding life-sustaining healthcare between
      emergency physicians (EP) and emergency registrars (ER). METHODS: This was a sub
      study of a prospective cross-sectional questionnaire-based case series conducted
      in six EDs. Primary outcomes were, which of the discussion and considerations,
      were rated most important by EP and ER in the decision-making process. RESULTS:
      We studied responses relating to the care of 320 patients, of which 49.4% were
      women and the median age was 83 (interquartile range [IQR] 72-88). EP and ER were
      sole decision-makers in 185 (39.7%) and 135 (30.0%) of cases, respectively.
      Treatment was withdrawn or withheld in 72.0 and 90.6% of all deaths by EP and ER,
      respectively (P < 0.001). EP and ER provided full treatment in 88 (34%) and 19
      (12.7%) of cases, respectively (P < 0.05). The consideration rated most important
      was prognosis: 165 (90.2%, confidence interval: 85.0-93.7) and 121 (90.3%,
      confidence interval: 84.1-94.2) for EP and ER, respectively. ER rated co
      morbidities and age more important than did EP (P < 0.05). Both rated discussions
      with family as very important. EP and ER referred 6.0% versus 11.9% patients to
      palliative care services, respectively. The proportion of patients taking longer
      than 24 h to die was higher for ER compared with that for EP (14.1% vs 4.9%, P <
      0.05). CONCLUSION: We found that ER were more likely to withdraw/withhold life
      sustaining healthcare, provide partial treatment, rate different considerations
      as important and their patients took longer to die than that of EP. Focused
      education and training might improve decision-making consistency between
      physicians and training registrars.

PMID- 27701846
TI  - Genetic and Phytochemical Analysis to Evaluate the Diversity and Relationships of
      Mate (Ilex paraguariensis A.St.-Hil.) Elite Genetic Resources in a Germplasm
      Collection.
AB  - The aim of this study was to evaluate the phytochemical and genetic diversity,
      relationships and identification of mate (Ilex paraguariensis A.St.-Hil.) elite
      genetic resources belonging to the Brazilian germplasm collection and mate
      breeding program. Mate has been studied due to the presence of phytochemical
      compounds, especially methylxanthines and phenolic compounds. The samples were
      collected from the leaves of 76 mate elite genetic resources (16 progenies * 5
      localities). Total DNA was extracted from mate leaves and 20 random primers were
      used for DNA amplification. Methylxanthines (caffeine and theobromine) and
      phenolic compounds (chlorogenic, neochlorogenic, and criptochlorogenic acids)
      were quantified by HPLC. The genetic divergence estimated was higher within (92%)
      than among (8%) the different populations. Analysis of genetic distance between
      origins provided the formation of two groups by UPGMA cluster analysis, with
      higher polymorphism (94.9%). The average content of caffeine ranged from 0.01 to
      1.38% and theobromine of 0.10 - 0.85% (w/w). The caffeoylquinic acids
      concentrations (1.43 - 5.38%) showed a gradient 3-CQA > 5-CQA > 4-CQA. The
      coefficient of genetic variation (CVg) was of low magnitude for all mono
      caffeoylquinics acids. Significant correlations (positive and negative) were
      observed between the phytochemical compounds. Genetic diversity analysis
      performed by RAPD markers showed a greater intra-populational diversity; genetic
      resources with low caffeine and higher theobromine content were identified and
      can be used in breeding programs; the correlation between methylxanthines and
      phenolic compounds can be used as a good predictor in future studies.

PMID- 27701847
TI  - Small but mighty: how minor components drive major biogeochemical cycles.

PMID- 27701848
TI  - Alcohol intoxication in non-motorised road trauma.
AB  - OBJECTIVE: To determine the proportion of non-motorised road users involved in
      road traffic crashes that presents to hospital intoxicated. METHODS: We undertook
      a retrospective cohort study using data collected from the Alfred Trauma
      Registry. All patients presenting to an adult major trauma centre in Victoria,
      Australia from July 2009 to June 2014 who were involved in a road traffic crash
      as a non-motorised road user - pedestrians, pedal-cyclists, non-motorised scooter
      users, horse riders - were included. Patients who had a blood alcohol measurement
      were included, and intoxication was defined as a blood alcohol concentration
      >=0.05 g/100 mL. RESULTS: There were 1323 patients included for analysis with
      data on presenting blood alcohol concentration. Alcohol was detected in 248
      (18.7%; 95% CI: 16.7-20.9) patients, whereas 211 (15.9%; 95% CI: 14.1-18.0) were
      intoxicated. Among all included pedestrians, 161 (24.7%) were intoxicated; among
      all included pedal-cyclists, 47 (7.3%) were intoxicated. Intoxicated patients
      were significantly younger, and a higher proportion were males and more likely to
      present after hours and on public holidays (P < 0.01). Survival to hospital
      discharge and inpatient rehabilitation requirements were similar among
      intoxicated and non-intoxicated patients. CONCLUSIONS: Intoxication was common
      among non-motorised road users, and the proportion of intoxicated patients in
      this subgroup appears unchanged over time despite public awareness programmes.
      The true burden of intoxication in non-motorised road users remains unknown
      because of a lack of routine testing. Legislation directed at testing for
      intoxication of non-motorised users and introduction of penalties should be
      considered to improve safety of all road users.

PMID- 27701850
TI  - Nominate a special colleague for the 2017 AANP State Award for Excellence.

PMID- 27701851
TI  - Consent to publish medical case reports.

PMID- 27701852
TI  - Intrinsic Base-Pair Rearrangement in the Hairpin Ribozyme Directs RNA
      Conformational Sampling and Tertiary Interface Formation.
AB  - Dynamic fluctuations in RNA structure enable conformational changes that are
      required for catalysis and recognition. In the hairpin ribozyme, the
      catalytically active structure is formed as an intricate tertiary interface
      between two RNA internal loops. Substantial alterations in the structure of each
      loop are observed upon interface formation, or docking. The very slow on-rate for
      this relatively tight interaction has led us to hypothesize a double
      conformational capture mechanism for RNA-RNA recognition. We used extensive
      molecular dynamics simulations to assess conformational sampling in the undocked
      form of the loop domain containing the scissile phosphate (loop A). We observed
      several major accessible conformations with distinctive patterns of hydrogen
      bonding and base stacking interactions in the active-site internal loop. Several
      important conformational features characteristic of the docked state were
      observed in well-populated substates, consistent with the kinetic sampling of
      docking-competent states by isolated loop A. Our observations suggest a hybrid or
      multistage binding mechanism, in which initial conformational selection of a
      docking-competent state is followed by induced-fit adjustment to an in-line,
      chemically reactive state only after formation of the initial complex with loop
      B.

PMID- 27701849
TI  - Short sleep duration and longer daytime napping are associated with non-alcoholic
      fatty liver disease in Chinese adults.
AB  - BACKGROUND: Epidemiologic studies have reported conflicting results on the
      relationship between short sleep duration and non-alcoholic fatty liver disease
      (NAFLD). There are no previous studies investigating the effect of daytime
      napping on NAFLD. In the present study we examined the associations between NAFLD
      and both nightly sleep duration and daytime napping in a middle-aged and elderly
      Chinese population. METHODS: This cross-sectional community-based population
      study was performed on 8559 individuals aged >=40 years. Sleep duration and the
      duration of daytime napping were self-reported using a standardized
      questionnaire; NAFLD was diagnosed by ultrasonography. RESULTS: In this study
      sample, the overall prevalence of NAFLD was 30.4%. There was an inverse
      association between sleep duration and the risk of prevalent NAFLD. In
      multivariate analysis, the odds ratios (ORs) and 95% confidence intervals (CIs)
      of prevalent NAFLD for decreasing sleep duration categories (>=9, 8.1-9, 7.1-8,
      6.1-7, and <=6.1 h) were 1.00 (reference), 1.38 (1.13-1.70), 1.32 (1.08-1.61),
      1.29 (1.04-1.60), and 1.66 (1.28-2.15), respectively (P trend  = 0.0073).
      Compared with participants without a daytime napping habit, nap takers with a
      longer nap duration (>0.5 h) had an increased risk of prevalent NAFLD (OR 1.22;
      95% CI 1.06-1.41). The associations of sleep duration and daytime napping
      duration with NAFLD were generally consistent across different categories of age
      and obesity, metabolic syndrome, and insulin resistance status. CONCLUSIONS:
      Short sleep duration and longer daytime napping were associated with an increased
      risk of prevalent NAFLD in a middle-aged and elderly Chinese population.

PMID- 27701853
TI  - Competitive Adsorption of Acetic Acid and Water on Kaolinite.
AB  - Mineral dust is prevalent in the atmosphere due to emissions from natural and
      anthropogenic sources. As mineral dust particles undergo long distance transport,
      they are exposed to trace gases and water vapor. We have characterized the
      interactions of acetic acid on kaolinite using Diffuse Reflectance Infrared
      Fourier Transform Spectroscopy and molecular modeling to determine the
      chemisorbed species present. After the addition of acetic acid, gas phase water
      was introduced to explore how water vapor competes with acetic acid for surface
      sites. We have found that four chemisorbed acetate species are found on kaolinite
      after exposure to acetic acid in which acetate bonds through a monodentate,
      bidenatate, or bidentate bridging linkage with an aluminum atom. These species
      exhibit varying levels of stability after the introduction of water, indicating
      that water vapor affects the adsorption of organic acids. These results indicate
      that the type of chemisorbed species determines its stability toward competitive
      adsorption, which has potential implications for atmospheric composition and ice
      nucleation.

PMID- 27701854
TI  - Deciphering the Spatial Arrangement of Metals and Correla-tion to Reactivity in
      Multivariate Metal-Organic Frameworks.
AB  - Thirty-six porphyrin based metal-organic frameworks (MOFs) with composition of
      (M3O)2(TCPP-M)3 and M3O trigonal SBUs of various metals, Mg3O, Mn3O, Co3O, Ni3O,
      and Fe3O including mixed-metal SBUs, MnxFe3-xO, NixFe3-xO, CoxNi3-xO, MnxCo3-xO,
      MnxMg3-xO, and MnxNi3-xO were synthesized and characterized. These multivariate
      MOFs (MTV-MOFs) were examined by X-ray photoelectron spectroscopy (XPS),
      ultraviolet-visible diffuse reflectance spectra (UV-vis DRS) and, for the first
      time, their metal spatial arrangement deciphered and found to exist in the form
      of either domains or well-mixed. We find that those MTV-MOFs with well-mixed
      metals in their SBUs, rather than the SBUs having one kind of metal but different
      from one SBU to another, perform better than the sum of their parts in the test
      reaction involving the photo-oxidation of 1,5-dihydroxynaphthalene (DHN) [for
      example, kobs = 1.03 h-1 for (Mn1.77Ni1.23O)2(TCPP-Ni)3].

PMID- 27701855
TI  - Kinetics of Dimethylated Thioarsenicals and the Formation of Highly Toxic
      Dimethylmonothioarsinic Acid in Environment.
AB  - Dimethylmonothioarsinic acid (DMMTAV) is a highly toxic, thiolated analogue of
      dimethylarsinic acid (DMAV). In comparison, a further thiolated analogue,
      dimethyldithioarsinic acid (DMDTAV), and DMAV both exhibit lower toxicity. To
      understand the environmental conditions responsible for forming DMMTAV, the
      kinetics of DMAV thiolation are examined. The thiolation of DMAV is pH-dependent
      and consists of two consecutive first-order reactions under excess sulfide
      conditions. The first thiolation of DMAV to form DMMTAV is faster than the second
      one to DMDTAV. DMMTAV is therefore an intermediate. The first reaction is first
      order in H2S at pH 6.0 and 20  degrees C; therefore, the overall reaction is
      second-order and the rate coefficient in this condition is 0.0780 M-1 s-1. The
      rate coefficient significantly decreases at pH 8.0, indicating that H2S(aq)
      triggers the thiolation of DMAV. The second reaction rate is significantly
      decreased at pH 2.5; therefore, reaction under strongly acidic conditions leads
      to accumulation of highly toxic DMMTAV in the early stages of thiolation. The
      transformation of DMDTAV to DMMTAV is catalyzed in the presence of ferric iron.
      Formation of DMMTAV should be considered when assessing risk posed by arsenic
      under sulfidic or sulfate reducing conditions.

PMID- 27701856
TI  - Protective effects of degraded soybean polysaccharides on renal epithelial cells
      exposed to oxidative damage.
AB  - This study aimed to investigate the protective effects of degraded soybean
      polysaccharides (DSP) on oxidatively damaged African green monkey kidney
      epithelial (Vero) cells. Low DSP concentration (10 MUg/mL) elicited an evident
      protective effect on H2O2-induced cell injury (0.3 mmol/L). The cell viabilities
      of the H2O2-treated group and the DSP-protected group were 57.3% and 93.1%,
      respectively. The cell viability decreased to 88.3% when the dosage was increased
      to 100 MUg/mL. DSP protected Vero cells from H2O2-mediated oxidative damage by
      enhancing cellular superoxide dismutase activity and total antioxidant capacity
      and by decreasing malonaldehyde content and lactate dehydrogenase release. The
      H2O2-treated cells stimulated the aggregation of calcium oxalate monohydrate
      crystals. DSP could also reduce the crystal size, decrease the attached crystal
      content, and prevent the cell aggregation by alleviating oxidative injury and
      lipid peroxidation, enhancing antioxidant capacity, and decreasing hyaluronan
      expression on cellular surfaces. The internalization ability of the injured cells
      was improved after these cells were exposed to DSP solution. The regulation
      ability of DSP-repaired cells on calcium oxalate dihydrate formation, crystal
      attachment, aggregation, and internalization was lower than that of normal cells
      but was higher than that of the injured cells. DSP may be a potential green drug
      to prevent CaOx stone formation because DSP could protect cells from oxidative
      damage and inhibit CaOx crystal formation.

PMID- 27701857
TI  - Novel TiO2/C3N4 Photocatalysts for Photocatalytic Reduction of CO2 and for
      Photocatalytic Decomposition of N2O.
AB  - TiO2/g-C3N4 photocatalysts with the ratio of TiO2 to g-C3N4 ranging from 0.3/1 to
      2/1 were prepared by simple mechanical mixing of pure g-C3N4 and commercial TiO2
      Evonik P25. All the nanocomposites were characterized by X-ray powder
      diffraction, UV-vis diffuse reflectance spectroscopy, photoluminescence, X-ray
      photoelectron spectroscopy, Raman spectroscopy, infrared spectroscopy,
      transmission electron microscopy, photoelectrochemical measurements, and nitrogen
      physisorption. The prepared mixtures along with pure TiO2 and g-C3N4 were tested
      for the photocatalytic reduction of carbon dioxide and photocatalytic
      decomposition of nitrous oxide. The pure g-C3N4 exhibited the lowest
      photocatalytic activity in both cases, pointing to a very high recombination rate
      of charge carriers. On the other hand, the most active photocatalyst toward all
      the products was (0.3/1)TiO2/g-C3N4. The highest activity is achieved by
      combination of a number of factors: (i) specific surface area, (ii) adsorption
      edge energy, (iii) crystallite size, and (iv) efficient separation of the charge
      carriers, where the efficient charge separation is the most decisive parameter.

PMID- 27701858
TI  - Effect of Aging and PCBM Content on Bulk Heterojunction Organic Solar Cells
      Studied by Intensity Modulated Photocurrent Spectroscopy.
AB  - A series of encapsulated and nonencapsulated bulk heterojunction photovoltaic
      devices containing poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61 butyric
      acid methyl ester (PCBM) with different P3HT:PCBM ratios were investigated using
      traditional steady-state as well as non-steady-state intensity modulated
      photocurrent spectroscopy (IMPS) techniques. The steady state J-V measurements
      showed that PCBM content did not have a significant effect on the efficiency for
      freshly prepared devices, whereas aged nonencapsulated devices exhibited a strong
      dependence on PCBM content. IMPS measurements showed a significant contribution
      of interfacial nongeminate recombination in nonencapsulated devices, which
      increased with decreasing PCBM content in the photoactive layer and cell aging.
      It was related to the formation of interfacial states at the P3HT/PCBM interface
      due to atmospheric contamination, which act as recombination centers. Device
      encapsulation was found to be effective in preventing the occurrence of
      interfacial recombination. Our results suggest that IMPS can be used as a
      diagnostic tool to predict the performance of bulk heterojunction organic solar
      cells. If a solar cell shows the presence of interfacial states as indicated by
      semicircle arcs in quadrant I of the IMPS complex plane plots, it is most likely
      that its performance will deteriorate with time due to enhanced interfacial
      recombination, even without further exposure to atmospheric contaminations. We
      conclude that interfacial nongeminate recombination is an important degradation
      mechanism in organic solar cells, especially in the case of exposure to
      atmospheric contaminants.

PMID- 27701860
TI  - Total Synthesis of Aquatolide: Wolff Ring Contraction and Late-Stage Nozaki
      Hiyama-Kishi Medium-Ring Formation.
AB  - A total synthesis of the highly strained natural product aquatolide has been
      achieved. The synthesis featured a photoinduced Wolff ring contraction reaction
      for the construction of bicyclo[2.1.1]hexane from diazo compound with a
      bicyclo[2.2.1]heptane skeleton. The eight-membered enone was built by a late
      stage intramolecular Nozaki-Hiyama-Kishi vinylation reaction of steric bulky
      vinyl iodide and aldehyde.

PMID- 27701861
TI  - Photoemission of Energetic Hot Electrons Produced via Up-Conversion in Doped
      Quantum Dots.
AB  - The benefits of the hot electrons from semiconductor nanostructures in
      photocatalysis or photovoltaics result from their higher energy compared to that
      of the band-edge electrons facilitating the electron-transfer process. The
      production of high-energy hot electrons usually requires short-wavelength UV or
      intense multiphoton visible excitation. Here, we show that highly energetic hot
      electrons capable of above-threshold ionization are produced via exciton-to-hot
      carrier up-conversion in Mn-doped quantum dots under weak band gap excitation
      (~10 W/cm2) achievable with the concentrated solar radiation. The energy of hot
      electrons is as high as ~0.4 eV above the vacuum level, much greater than those
      observed in other semiconductor or plasmonic metal nanostructures, which are
      capable of performing energetically and kinetically more-challenging electron
      transfer. Furthermore, the prospect of generating solvated electron is unique for
      the energetic hot electrons from up-conversion, which can open a new door for
      long-range electron transfer beyond short-range interfacial electron transfer.

PMID- 27701859
TI  - HIV-1 Capsid Function is Regulated by Dynamics: Quantitative Atomic-Resolution
      Insights by Integrating Magic-Angle-Spinning NMR, QM/MM, and MD.
AB  - HIV-1 CA capsid protein possesses intrinsic conformational flexibility, which is
      essential for its assembly into conical capsids and interactions with host
      factors. CA is dynamic in the assembled capsid, and residues in functionally
      important regions of the protein undergo motions spanning many decades of
      timescales. Chemical shift anisotropy (CSA) tensors, recorded in magic-angle
      spinning NMR experiments, provide direct residue-specific probes of motions on
      nano- to microsecond timescales. We combined NMR, MD, and Density-Functional
      Theory calculations, to gain quantitative understanding of internal backbone
      dynamics in CA assemblies, and found that the dynamically averaged 15N CSA
      tensors calculated by this joined protocol are in remarkable agreement with
      experiment. Thus, quantitative atomic-level understanding of the relationships
      between CSA tensors, local backbone structure and motions in CA assemblies is
      achieved, demonstrating the power of integrating NMR experimental data and theory
      for characterizing atomic-resolution dynamics in biological systems.

PMID- 27701862
TI  - Room-Temperature Surface Modification of Cu Nanowires and Their Applications in
      Transparent Electrodes, SERS-Based Sensors, and Organic Solar Cells.
AB  - Cu nanowires (Copper nanowires) have attracted lots of attention recently due to
      their potential applications in transparent electrodes, surface enhanced Raman
      scattering (SERS) based sensors, and solar cells. However, as the surface
      composition and morphology of Cu nanowires severely influence the performance of
      the devices based on them, facile surface modification methods need to be
      developed. Herein, we propose a room-temperature, time-saving aqueous solution
      method, through which clean Cu nanowires with small Ag nanoparticles decorating
      around them could be achieved. The unique "sesame candy bar" structure of Cu
      nanowires brought about significant enhancement on the electrical, optical, and
      mechanical performances of Cu nanowire networks. Transparent electrodes with
      ideal opto-electrical performance (47 Omega sq-1 @ 89.1% T) and high
      antioxidation, antithermal, and electrical stability were fabricated. Stretchable
      electrodes based on the modified Cu nanowire networks showed superior stretch
      ability and cyclic stability. SERS sensors and organic solar cells based on Cu
      nanowire networks exhibited high performance due to the enhanced surface
      plasmonic coupling and light scattering effect. We believe that the method will
      shed light on the large-scale fabrication and application of Cu nanowire based
      devices.

PMID- 27701863
TI  - Laser Level Scheme of Self-Interstitials in Epitaxial Ge Dots Encapsulated in Si.
AB  - Recently, it was shown that lasing from epitaxial Ge quantum dots (QDs) on Si
      substrates can be obtained if they are partially amorphized by Ge ion bombardment
      (GIB). Here, we present a model for the microscopic origin of the radiative
      transitions leading to enhanced photoluminescence (PL) from such GIB-QDs. We
      provide an energy level scheme for GIB-QDs in a crystalline Si matrix that is
      based on atomistic modeling with Monte Carlo (MC) analysis and density functional
      theory (DFT). The level scheme is consistent with a broad variety of PL
      experiments performed on as-grown and annealed GIB-QDs. Our results show that an
      extended point defect consisting of a split-[110] self-interstitial surrounded by
      a distorted crystal lattice of about 45 atoms leads to electronic states at the
      Gamma-point of the Brillouin zone well below the conduction band minimum of
      crystalline Ge. Such defects in Ge QDs allow direct transitions of electrons
      localized at the split-interstitial with holes confined in the Ge QD. We identify
      the relevant growth and annealing parameters that will let GIB-QDs be employed as
      an efficient laser active medium.

PMID- 27701864
TI  - InAs Colloidal Quantum Dots Synthesis via Aminopnictogen Precursor Chemistry.
AB  - Despite their various potential applications, InAs colloidal quantum dots have
      attracted considerably less attention than more classical II-VI materials because
      of their complex syntheses that require hazardous precursors. Recently, amino
      phosphine has been introduced as a cheap, easy-to-use and efficient phosphorus
      precursor to synthesize InP quantum dots. Here, we use aminopnictogen precursors
      to implement a similar approach for synthesizing InAs quantum dots. We develop a
      two-step method based on the combination of aminoarsine as the arsenic precursor
      and aminophosphine as the reducing agent. This results in state-of-the-art InAs
      quantum dots with respect to the size dispersion and band-gap range. Moreover, we
      present shell coating procedures that lead to the formation of InAs/ZnS(e)
      core/shell quantum dots that emit in the infrared region. This innovative
      synthesis approach can greatly facilitate the research on InAs quantum dots and
      may lead to synthesis protocols for a wide range of III-V quantum dots.

PMID- 27701865
TI  - 3D Structures of Responsive Nanocompartmentalized Microgels.
AB  - Compartmentalization in soft matter is important for segregating and coordinating
      chemical reactions, sequestering (re)active components, and integrating
      multifunctionality. Advances depend crucially on quantitative 3D visualization in
      situ with high spatiotemporal resolution. Here, we show the direct visualization
      of different compartments within adaptive microgels using a combination of in
      situ electron and super-resolved fluorescence microscopy. We unravel new levels
      of structural details and address the challenge of reconstructing 3D information
      from 2D projections for nonuniform soft matter as opposed to monodisperse
      proteins. Moreover, we visualize the thermally induced shrinkage of responsive
      core-shell microgels live in water. This strategy opens doors for systematic in
      situ studies of soft matter systems and their application as smart materials.

PMID- 27701866
TI  - Elasticity, adhesion and tether extrusion on breast cancer cells provide a
      signature of their invasive potential.
AB  - We use single cell force spectroscopy to compare elasticity, adhesion and tether
      extrusion on four breast cancer cell lines with an increasing invasive potential.
      We perform cell attachment/detachment experiments either on fibronectin or on
      another cell using an Atomic Force Microscope. Our study on the membrane tether
      formation from cancer cells show that they are easier to extrude from aggressive
      invasive cells. Measured elastic modulus values confirm that more invasive cells
      are softer. Moreover, the adhesion force increases with the invasive potential.
      Our results provide a mechanical signature of breast cancer cells that correlates
      with their invasivity.

PMID- 27701867
TI  - Approach Based on Polyelectrolyte-Induced Nanoassemblies for Enhancing
      Sensitivity of Pyrenyl Probes.
AB  - We have developed a unique approach for enhancing the sensitivity of pyrenyl
      probes based on polyelectrolyte-induced nanoassemblies and explored its sensing
      application toward 2,4,6-trinitrophenol (TNP). The key issue of the method is the
      formation of the nanoassemblies which possess high-density charges, specific
      surface area, and inner hydrophobic regions. These properties would help increase
      the loading of analytes and promote probe-analyte interactions, thereby leading
      to the prominent enhancement of the sensitivity. In the course of TNP detection,
      pyrene nanoassemblies can bind TNP efficiently through cooperative noncovalent
      interactions including electrostatic, pi-pi stacking, and charge-transfer
      interactions, resulting in the distinct fluorescent responses of pyrene moieties.
      This system has excellent selectivity and sensitivity for TNP detection. The
      detection limit is as low as 5 nM. It may be used for monitoring the TNP
      concentrations in real-world samples.

PMID- 27701868
TI  - Tailorable and Wearable Textile Devices for Solar Energy Harvesting and
      Simultaneous Storage.
AB  - The pursuit of harmonic combination of technology and fashion intrinsically
      points to the development of smart garments. Herein, we present an all-solid
      tailorable energy textile possessing integrated function of simultaneous solar
      energy harvesting and storage, and we call it tailorable textile device. Our
      technique makes it possible to tailor the multifunctional textile into any
      designed shape without impairing its performance and produce stylish smart energy
      garments for wearable self-powering system with enhanced user experience and more
      room for fashion design. The "threads" (fiber electrodes) featuring tailorability
      and knittability can be large-scale fabricated and then woven into energy
      textiles. The fiber supercapacitor with merits of tailorability, ultrafast
      charging capability, and ultrahigh bending-resistance is used as the energy
      storage module, while an all-solid dye-sensitized solar cell textile is used as
      the solar energy harvesting module. Our textile sample can be fully charged to
      1.2 V in 17 s by self-harvesting solar energy and fully discharged in 78 s at a
      discharge current density of 0.1 mA.

PMID- 27701869
TI  - Nanosizing a Metal-Organic Framework Enzyme Carrier for Accelerating Nerve Agent
      Hydrolysis.
AB  - We report the synthesis and characterization of a water-stable zirconium metal
      organic framework (MOF), NU-1003, featuring the largest mesoporous aperture known
      for a zirconium MOF. This material has been used to immobilize the nerve agent
      hydrolyzing enzyme, organophosphorus acid anhydrolase (OPAA). The catalytic
      efficiency of immobilized OPAA in nanosized NU-1003 is significantly increased
      compared to that of OPAA immobilized in microsized NU-1003 and even exceeds that
      of the free OPAA enzyme. This paper highlights a method for rapid and highly
      efficient hydrolysis of nerve agents using nanosized enzyme carriers.

PMID- 27701871
TI  - Resistance patterns to anti-PD-1 therapy in metastatic melanoma.

PMID- 27701872
TI  - Does hepatitis B virus infection cause breast cancer?
AB  - Lifestyle and family history are two of the most important risk factors for
      breast cancer (BC). However, these risk factors cannot explain the differences in
      the incidence and early BC onset among Chinese females compared to their western
      counterparts. We propose in this hypothesis the potential mechanism of indirect
      oncogenesis of hepatitis B virus (HBV) in causing BC through its persistence as
      occult infection and continuous replication with long term subtle liver damage.
      Estrogen is mainly deactivated in the liver and long term necro-inflammatory
      damage to liver may result in persistent high level of estrogen, which is a
      dominant risk factor for BC. HBV may also directly affect the breast cells
      through its cis and trans effects of HBx which may act as oncoprotein. Given the
      recognised aetiologic association between oestrogen and breast cancer risk, there
      is biological plausibility that dietary soy and vegetable intake which is rich in
      the Chinese diet may have anti-carcinogenic effect on the breast. The seemingly
      conflicting phenomenon of early age onset and lower BC incidence in China might
      be due to wide imbalance in the amount of exposure to carcinogenic factor (e.g.,
      HBV infection) for decades and the carcinoprotective exposure levels (e.g.,
      isoflavonoids and flavonoids intake). For example, the increase in
      carcinoprotective levels would lead to lower incidence of breast cancer and vice
      versa. Although the focus of this personal view is on HBV, this by no means
      negates the roles of other known risk factors in breast-cancer development.
      Characterisation of the role of HBV in BC could potentially benefit Chinese
      females by decreasing incidence and increasing overall survival.

PMID- 27701873
TI  - Adjuvant therapy for resected biliary tract cancer: a review.
AB  - Surgical resection remains the most important treatment for patients with biliary
      tract cancer (BTC), but despite radical surgical techniques many patients
      ultimately develop recurrent disease. BTC encompasses several distinct disease
      entities-intrahepatic, perihilar and distal bile duct cholangiocarcinoma as well
      as gallbladder cancer. These tumors are histologically similar, but have
      different etiologies and recent information regarding their genomic footprint has
      questioned their biological similarity. Surgical approaches are also necessarily
      varied based on the site of the tumor. Due to the poor survival rates seen in
      this disease, there has been significant effort to investigate chemotherapy and
      radiotherapy as adjuvants in patients whose disease has been successfully
      resected. The majority of the published evidence supporting this treatment relies
      on retrospective series or limited prospective studies, making interpretation
      difficult and complicating treatment decisions. This review summarizes the data
      regarding these adjunctive therapies.

PMID- 27701874
TI  - Initial assessment of patients without cognitive failure admitted to palliative
      care: a validation study.
AB  - OBJECTIVE: Many assessment tools have been developed for palliative care and
      there are a number of differences between them. Therefore, we felt that there was
      room for improvement. METHODS: In a previous study, the relevant items were
      selected by a Delphi process with international experts in palliative care. A 5
      point verbal scale was added to the items selected and adapted to the different
      kind of items. RESULTS: The study included 123 patients, 63 (51%) were female and
      the median age was 64 (37 to 88). A four-factor structure was found through the
      principal components analysis, explaining 60.1% of the total variance. The scale
      presented good reliability, with a Cronbach's alpha of 0.72. It was hypothesized
      as a validity of construct that as the total symptom burden increased, survival
      time would decrease. This hypothesis was confirmed by the statistical analysis
      performed. A hazard ratio of 1.016 (P=0.019) was obtained in the Cox regression
      model including the final score as an explanatory variable of survival time,
      which means that for each increment of 1% in the total score, there was an
      increased risk of death of 1.6%. CONCLUSIONS: This tool is in accordance with the
      recommended characteristics that an assessment tool should have. It is simple to
      administer and easy to explain, complete and analyze. It is also a valid tool.

PMID- 27701876
TI  - Radiation therapy for the treatment of skin Kaposi sarcoma.
AB  - OBJECTIVE: Kaposi sarcoma (KS) lesions are purplish, reddish blue or dark
      brown/black macules, plaques or nodules which involve the skin and occasionally
      internal organs. Most patients with KS have a long indolent chronic course.
      METHODS: A retrospective review was undertaken for all KS skin patients treated
      with radiotherapy at a tertiary cancer centre from Jan. 2, 1999 to Dec. 31, 2014
      (inclusive). RESULTS: A total of 47 patients with KS (43 classical, 0 African, 1
      iatrogenic, 3 AIDS related) were seen in the multidisciplinary clinic. Out of
      this group, 17 patients (5 females and 12 males, 14 classical, 0 African, 0
      iatrogenic, 3 AIDS related) with 97 KS skin sites were treated with local
      external beam radiotherapy. An additional 18 skin sites were treated with repeat
      radiotherapy. The radiotherapy dose ranged from 6 Gy in 1 fraction to 30 Gy in 10
      fractions with the most common dose fractionation scheme being 8 Gy in 1 fraction
      or 20 Gy in 5 daily fractions. For the previously untreated KS sites, 87%
      responded to radiation [30% complete response (CR) and 57% partial response
      (PR)]. Thirteen percent of KS sites treated with radiation progressed. For the
      skin sites which were treated with repeat radiotherapy, 0% showed CRs, 50% PRs
      and 50% had continued progression. CONCLUSIONS: The majority of KS skin lesions
      (87%) responded to radiotherapy. Patients experience minimal side effects from
      the palliative radiation regimens used. KS skin lesions which progress despite
      radiation are unlikely to show CR with repeat radiotherapy. In our experience 50%
      of skin KS will have partial regression with repeat radiotherapy and 50% will
      have continued progression.

PMID- 27701875
TI  - Possible role of aprepitant for intractable nausea and vomiting following whole
      brain radiotherapy-a case report.
AB  - Radiation-induced nausea and vomiting (RINV) is one of the most distressing
      symptoms that adversely affects quality of life (QOL) as well as the ongoing
      management plan of cancer patients. Although there are protocols for management
      of chemotherapy induced nausea and vomiting (CINV) but such guidelines are still
      lacking for RINV. Various agents like 5-hydroxy tryptophan 3 (5-HT3) antagonist,
      dexamethasone, metoclopramide and haloperidol are used in clinical practice for
      RINV but the results are not very encouraging. Because of proposed similarity in
      the mechanism of nausea and vomiting following chemotherapy and radiotherapy,
      aprepitant, a substance P neurokinin 1 receptor antagonist can be an optimal
      agent for RINV on account of its unique pharmacological property. We report a
      case of metastatic carcinoma breast with bilateral cerebellar metastasis. She
      presented with complaints of headache and intractable nausea and vomiting. A
      single fraction whole brain radiotherapy (WBRT) was given for bilateral
      cerebellum metastasis which further precipitated her symptoms. The prophylactic
      and therapeutic efficacy of antiemetic used for RINV may be enhanced by adding
      aprepitant before starting radiotherapy in high risk cases as in ours.

PMID- 27701877
TI  - Is the French palliative care policy effective everywhere? Geographic variation
      in changes in inpatient death rates among older patients in France, 2010-2013.
AB  - OBJECTIVE: Recently, French policymakers have tried to improve care at the end-of
      life, by improving access to community-based palliative care, particularly for
      patients with cancer and neurological diseases. If effective, these efforts
      should reduce the proportion of such patients who die in the hospital. In light
      of these policies, we sought to determine the effectiveness of these efforts on
      reducing inpatient deaths by conducting a retrospective, observational analysis
      of patients aged 65 and older who were admitted to hospitals in France between
      2010 and 2013 for 1 of 3 non-surgical conditions. METHODS: We calculated
      department-specific age- and sex-adjusted inpatient death rates for 3 types of
      nonsurgical admissions and modeled expected number of inpatient deaths had their
      rates for patients with cancer or neurological disease tracked those of patients
      with non-cancer non-neurological diseases. RESULTS: We found that patients
      admitted with a cancer diagnosis experienced 20,394 (13.0%) fewer inpatient
      deaths that expected had non-surgical cancer diagnosis admission rates tracked
      those of nonsurgical non-cancer and non-neurological admission rates; patients
      admitted with a primary neurological disease diagnosis experienced 513 (4.5%)
      fewer inpatient deaths than expected. During the study period, observed-to
      expected inpatient deaths fell more dramatically and consistently for patients
      admitted with cancer diagnoses than for those admitted with neurological
      diseases. Observed-to-expected ratios fell least in departments that were on the
      periphery of the French mainland. CONCLUSIONS: Our findings suggest that, in
      France, efforts to reduce inpatient death rates among patients with cancer or
      neurological disease diagnoses appear to be effective. However, their
      effectiveness varies geographically, suggesting that targeted efforts to improve
      lower performing departments may generate substantial performance improvements.

PMID- 27701878
TI  - Radiotherapy for brain metastases: quo vadis?

PMID- 27701879
TI  - Correlating symptoms and their changes with survival in patients with brain
      metastases.
AB  - OBJECTIVE: Having a clear prognosis for patients with brain metastases allows
      health care practitioners (HCPs) to determine appropriate palliative management
      and assist patients when making informed treatment decisions. The objective of
      this study was to determine the prognostic significance of commonly experienced
      symptoms as well as their changes. METHODS: Overall survival (OS) was calculated
      from the date of consultation for palliative radiotherapy to date of death or
      censored at last follow-up date. Symptom changes at follow up were defined as
      worsened, improved, or no change. Univariate and multivariate cox proportional
      hazard (PH) model of OS was conducted on 14 symptoms at baseline and on changes
      in those symptoms at 1-, 2-, and 3-month follow-ups. RESULTS: From 1999 to 2013,
      1,660 patients were included for baseline symptom analysis. Through univariate
      analysis, fatigue, nausea, appetite loss, coordination, concentration, balance
      and depression were significantly related to OS. Upon multivariate analysis,
      fatigue and appetite loss were most predictive of short survival. For symptom
      change, 201 patients were included. The actuarial median OS was 5.0 months [95%
      confidence interval (CI): 4.3-7.0], 7.1 months (95% CI: 5.2-9.5) and 8.8 months
      (95% CI: 5.8-11.5) for patients with month 1, 2, and 3 follow-ups, respectively.
      The most common symptom changes following whole brain radiotherapy (WBRT) were:
      worsened fatigue, appetite loss, and weakness. Worsened difficulty concentrating,
      fatigue, nausea and headaches were most predictive of a poorer survival outcome.
      CONCLUSIONS: HCPs should be aware of the shorter prognosis associated with
      patients exhibiting one or more of these symptoms and tailor care accordingly to
      maximize patients' remaining quality of life (QOL).

PMID- 27701880
TI  - Palliative care units in lung cancer in the real-world setting: a single
      institution's experience and its implications.
AB  - OBJECTIVE: Palliative care plays a crucial role in the overall management of
      patients with advanced lung cancer and was shown to lead to clinically meaningful
      improvement in quality of life, less aggressive endof-life care, and potentially
      prolonged survival. Here we summarize our single institution experience on
      palliative care in patients with lung cancer. METHODS: The data of patients with
      lung cancer treated at the palliative care unit of the Medical University of
      Vienna between June 2010 and March 2013 were retrospectively reviewed. Patient
      characteristics, reasons for admissions, treatment as well as interventions
      during hospitalization, and clinical outcomes were determined. RESULTS: The study
      enrolled 91 lung cancer patients, who represented 19.8% of the 460 patients
      admitted to the palliative care unit. They had the following clinical
      characteristics: 39% females, 61% males; median age 62 years; median Karnofsky
      performance status 50%, 92% metastatic disease, 74% non-small cell lung cancer
      (NSCLC), 19% small-cell lung cancer (SCLC), 7% neuroendocrine carcinomas of the
      lung. Primary reasons for admission were deterioration of performance status in
      40%, uncontrolled cancer-related pain in 38%, dyspnea in 13%, and psychosocial
      factors in 8% of the patients. Median duration of hospitalization was 16 days
      (range, 1-101 days). Improvement or stabilisation of tumor-related symptoms was
      achieved in 25% of the patients. Seventy-five percent of all patients died during
      their first admission. Their median survival from primary diagnosis until death
      was 16 months (95% confidence interval, 13.7-18.3 months). CONCLUSIONS: Patients
      with lung cancer admitted to the palliative care unit had late-stage disease. In
      order to provide early palliative care, the management of lung cancer patients
      should guarantee access to ambulatory care, inpatient care and home care as well
      as cooperation and communication between oncologists and palliative care
      physicians.

PMID- 27701881
TI  - The use of a segmental endoscopic score may improve the prediction of clinical
      outcomes in acute severe ulcerative colitis.
AB  - BACKGROUND: Acute severe colitis (ASC) remains a challenging complication of
      ulcerative colitis. The early identification of patients who will not respond to
      optimal therapy is warranted. Increasing evidence suggests that endoscopy may
      play a role in predicting important outcomes in acute severe colitis. METHODS:
      The endoscopic activity of consecutive patients with acute severe colitis was
      evaluated using the Mayo endoscopic sub-score (Mayo) and the ulcerative colitis
      endoscopic index of severity (UCEIS). Two segmental indexes were also produced by
      summing the scores of the rectum and sigmoid (seg-Mayo and seg-UCEIS,
      respectively). Endpoints included the need for salvage therapy with infliximab or
      cyclosporine, refractoriness to corticosteroids, and colectomy. RESULTS: Of one
      hundred and eight patients enrolled in the study, 60 (55.6%) were male; with a
      median age of 34.5 years (range 15-80). All patients received intravenous
      steroids. Fifty-nine patients (55.6%) showed an incomplete or absent response to
      steroids, 35 patients (34.3%) received salvage therapy with infliximab or
      cyclosporine and 38 patients (33.3%) were colectomized during the index
      hospitalization or within the first year of follow-up. All scores were able to
      predict the need for surgery, but only the seg-UCEIS significantly predicted
      refractoriness to steroids. CONCLUSIONS: There was a strong correlation between
      endoscopic severity and unfavorable outcomes. The UCEIS outperformed the Mayo
      endoscopic sub-score in all important outcomes. Segmental scoring further
      improved the performance of the UCEIS.

PMID- 27701882
TI  - A single institution's 21-year experience with surgically resected pancreatic
      neuroendocrine tumors: an analysis of survival and prognostic factors.
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) comprise a heterogeneous
      group of tumors with a varied biological behavior. In the present study, we
      analyzed the experience of 79 pNETs resected between 1999 and 2014. The
      pathologic prognostic factors (European Neuroendocrine Tumor Society, ENETS; and
      AJCC) classification, vascular invasion (VI), proliferation index (ki-67) and the
      presence of necrosis were retrospectively reviewed. METHODS: The clinical data of
      79 patients with pNETs who underwent surgery were retrospectively analyzed.
      Mortality rates and Kaplan-Meier estimates were used to evaluate survival over
      time for pathologic stages, tumor functionality, and vascular invasion. Cox
      proportional hazards models were used to calculate the hazard ratio regarding
      ENETS, AJCC staging, sex, tumor functionality and vascular invasion. RESULTS: The
      male:female ratio was 40:39. Twenty-one patients (26%) had functional tumors and
      58 (73.4%) had non-functional tumors, of which 35 (44.3%) were diagnosed
      incidentally. Seventeen Whipple procedures, 46 distal pancreatectomies (including
      26 laparoscopic and 20 open procedures), 8 laparoscopic central pancreatectomies,
      1 laparoscopic resection of the uncinated process and 7 enucleations (one
      laparoscopic) were performed. Vascular invasion and necrosis were observed in 29
      of 75 cases (38.6%) and in 16 cases (29%), respectively. The comparison between
      survivor functions of ENETS staging categories showed statistically significant
      differences (p = 0.042). Mortality rate was higher in patients with non
      functioning tumors compared with hormonally functioning tumors (p = 0.052) and in
      those with vascular invasion (p = 0.186). CONCLUSIONS: In spite of the
      heterogeneity of pNETs, the ENETS TNM classification efficiently predicts long
      term prognosis. The non-functioning tumors and the presence of vascular invasion
      are associated with poor prognosis.

PMID- 27701883
TI  - Validation of the computed assessment of cleansing score with the Mirocam(r)
      system.
AB  - BACKGROUND AND AIMS: A computed assessment of cleansing (CAC) score was developed
      to objectively evaluate small-bowel cleansing in the PillCam(r) capsule endoscopy
      (CE) system and to overcome the subjectivity and complexity of previous scoring
      systems. Our study aimed to adapt the CAC score to the Mirocam(r) system,
      evaluate its reliability with the Mirocam(r) CE system and compare it with three
      validated subjective grading scales. PATIENTS AND METHODS: Thirty CE were
      prospectively and independently reviewed by two authors who classified the degree
      of small-bowel cleanliness according to a quantitative index, a qualitative
      evaluation and an overall adequacy assessment. The authors were blinded for the
      CAC score of each CE, which was calculated as ([mean intensity of the red
      channel]/[mean intensity of the green channel] - 1) x 10. The mean intensities of
      the red and green channels of the small-bowel segment of the "Map View" bar in
      the Miroview Client(r) were determined using the histogram option of two photo
      editing software. RESULTS: There was a strong agreement between both CE readers
      for each of the three subjective scales used. The reproducibility of the CAC
      score was excellent and identical results were obtained with the two photo
      editing software. Regarding the comparison between the CAC score and the
      subjective scales, there was a moderate-to-good agreement with the quantitative
      index, qualitative evaluation and overall adequacy assessment. CONCLUSIONS: CAC
      score represents an objective and feasible score in the assessment of small-bowel
      cleansing in the Mirocam(r) CE system, and could be used per se or as part of a
      more comprehensive score.

PMID- 27701884
TI  - Ultrasound-assisted technique for challenging jejunostomy balloon-tube
      replacements.
AB  - The authors present a case of a 38-year-old man with a 4-hour history of
      accidental removal of a jejunostomy balloon-tube replacement (PEG-18-BRT-S, Cook
      Medical Inc., Bloomington, USA). The patient had undergone a direct percutaneous
      endoscopic jejunostomy (DPEJ) ten months ago, before chemoradiotherapy treatment
      for an esophageal squamous-cell carcinoma (uT3N2cM0). His past medical condition
      included alcoholic liver disease and distal gastrectomy from a life-threatening
      duodenal bleeding ulcer.

PMID- 27701885
TI  - Pseudomelanosis duodeni: is there a common denominator?
AB  - A 76-year-old female patient with a past medical history of diabetes mellitus,
      stage 3 chronic renal failure and iron deficiency anemia was referred for
      esophagogastroduodenoscopy (EGD) for evaluation of solid food dysphagia. She had
      been on oral therapy with ferrous sulfate for several years. Besides a Schatzki's
      ring the EGD revealed a duodenal mucosa with black-speckled pigmentation.
      Biopsies were performed and disclosed the deposition of brown (hemosiderin)
      pigment within macrophages in the lamina propria of normal villi. This endoscopic
      appearance is called pseudomelanosis duodeni (PD).

PMID- 27701886
TI  - Nodular colitis: endoscopic image an unusual finding.
AB  - An 82-year-old male with a history of high blood pressure, COPD, chronic myeloid
      leukemia, and stage-4 chronic renal failure. Admitted to hospital for lower-limb
      cellulitis and severe COPD exacerbation, he received antibiotic therapy and
      bronchodilators. During his hospital stay he developed severe anemia and had an
      hematochezia event with no diarrhea. A complete colonoscopy found small (4-7 mm)
      nacreous elevated lesions, circumferential in shape, in the cecum and ascending
      colon with some bleeding stigmata and submucosal bleeding suggestive of
      infectious colitis; stool culture was negative and Clostridium difficile toxins
      were positive. The condition was histologically confirmed.

PMID- 27701887
TI  - A typical but seldom recognized foreign body in the esophagus of a
      laryngectomized patient.
AB  - A 57-year-old man with a past medical history of total laryngectomy for squamous
      cell carcinoma of the larynx was admitted to our institution 5 months after the
      procedure, for surgical resection of a local recurrence of the tumor. In the
      postoperative period, endoscopically guided placement of a nasogastric tube was
      scheduled, after previous failed attempts. Upper gastrointestinal endoscopy
      revealed an anastomotic dehiscence, 13 cm distal to the incisors, and a foreign
      body penetrating through the esophageal wall, 20cm distal to the incisors. We
      were unable to identify the foreign body with certainty but, after consulting
      with the assistant otorhinolaryngologist, we realized that it was a voice
      prosthesis.

PMID- 27701888
TI  - Acute abdomen from duodenal diverticulitis. A case report.
AB  - Duodenal diverticula are a rare, usually asymptomatic clinical condition. When a
      complication arises clinical suspicion is key for the diagnosis. On occasion
      these patients receive a delayed diagnosis and undergo inadequate medical
      therapy. We report the case of a patient with evidence of duodenal diverticulitis
      in association with gallbladder inflammation by contiguity, as well as his
      diagnosis and management.

PMID- 27701889
TI  - Fatal Campylobacter jejuni ileocolitis.
AB  - Campylobacter infection usually starts in the jejunum and ileum and progresses
      distally. The case fatality rate is low and most occur in elderly or patients
      with comorbidity as in this case. Antibiotics should be used in severe cases or
      patients at risk. The choices are macrolides and fluoroquinolones. However, in
      some countries quinolone resistance is increasing, as in Spain. We shouldn't
      forget this fact for the proper treatment approach and specifically in refractory
      cases.

PMID- 27701890
TI  - Contribution of military psychology in supporting those in rural and remote work
      environments.
AB  - CONTEXT: This article explores the relevance of the body of military psychology
      knowledge to the management and support of those living and working in
      rural/remote industries and locations, particularly within Australia. ISSUES: For
      those who live and work in rural/remote settings, there are social, occupational,
      health and environmental challenges. Some of these are shared with families and
      individuals who are associated with military life. The published literature on
      the shared attributes between military and rural/remote work environments rarely
      makes a direct link. However, looking at both areas suggests opportunities for
      the application of psychological knowledge in the well-developed field of
      military psychology to the rural/remote setting. This article focuses on
      application of psychological knowledge in the areas of occupational performance,
      fatigue, mental health, family care and in the training of psychologists to work
      in rural/remote areas. LESSONS LEARNED: The cross-pollination of knowledge
      between those working with military personnel and family and those working in
      rural/remote settings should allow practitioners greater opportunities to improve
      health and wellbeing outcomes in these communities.

PMID- 27701891
TI  - Recent advances in targeting the fatty acid biosynthetic pathway using fatty acid
      synthase inhibitors.
AB  - INTRODUCTION: Elevated lipogenesis has been associated with a variety of diseases
      including obesity, cancer and nonalcoholic fatty liver disease (NAFLD). Fatty
      acid synthase (FASN) plays a pivotal role in de novo lipogenesis, making this
      multi-catalytic protein an attractive target for therapeutic intervention.
      Recently, the first FASN inhibitor successfully advanced through the drug
      development process and entered clinical evaluation in oncology. Areas covered:
      This review discusses the biological roles of FASN in three prominent disease
      areas: cancer, obesity-related disorders and NAFLD. Recent advances in drug
      discovery strategies and design of newer FASN inhibitors are also highlighted.
      Expert opinion: Despite the abundance of evidence linking the lipogenic pathway
      to cancer, progression of FASN-targeted molecules has been rather slow and
      challenging and no compounds have moved past the preclinical phase. The landscape
      has recently changed with the recent advancement of the first FASN inhibitor into
      clinical evaluation for solid tumors. Needless to say, the successful translation
      into the clinical setting will open opportunities for expanding the therapeutic
      utility of FASN inhibitors not just in oncology but in other diseases associated
      with elevated lipogenesis such as obesity, type 2 diabetes, and NAFLD.

PMID- 27701892
TI  - Intelligent polymeric micelles: development and application as drug delivery for
      docetaxel.
AB  - Recent years, docetaxel (DTX)-loaded intelligent polymeric micelles have been
      regarded as a promising vehicle for DTX for the reason that compared with
      conventional DTX-loaded micelles, DTX-loaded intelligent micelles not only
      preserve the basic functions of micelles such as DTX solubilization, enhanced
      accumulation in tumor tissue, and improved bioavailability and biocompatibility
      of DTX, but also possess other new properties, for instance, tumor-specific DTX
      delivery and series of responses to endogenous or exogenous stimulations. In this
      paper, basic theories and action mechanism of intelligent polymeric micelles are
      discussed in detail, especially the related theories of DTX-loaded stimuli
      responsive micelles. The relevant examples of stimuli-responsive DTX-loaded
      micelles are also provided in this paper to sufficiently illustrate the
      advantages of relevant technology for the clinical application of anticancer
      drug, especially for the medical application of DTX.

PMID- 27701893
TI  - Recent trends in the transdermal delivery of therapeutic agents used for the
      management of neurodegenerative diseases.
AB  - With the increasing proportion of the global geriatric population, it becomes
      obvious that neurodegenerative diseases will become more widespread. From an
      epidemiological standpoint, it is necessary to develop new therapeutic agents for
      the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis
      and other neurodegenerative disorders. An important approach in this regard
      involves the use of the transdermal route. With transdermal drug delivery systems
      (TDDS), it is possible to modulate the pharmacokinetic profiles of these
      medications and improve patient compliance. Transdermal drug delivery has also
      been shown to be useful for drugs with short half-life and low or unpredictable
      bioavailability. In this review, several transdermal drug delivery enhancement
      technologies are being discussed in relation to the delivery of medications used
      for the management of neurodegenerative disorders.

PMID- 27701894
TI  - Whole blood samples for adrenocorticotrophic hormone measurement can be stored at
      room temperature for 4 hours.
AB  - INTRODUCTION: The aim of this study was to investigate and compare the stability
      of adrenocorticotrophic hormone (ACTH) in whole blood stored on ice and at room
      temperature for up to 48 hours. This study differs from previous studies by a
      larger data material. MATERIALS AND METHODS: EDTA-blood samples from 30 patients
      were collected, aliquoted and stored on ice or at room temperature for 0, 2, 4,
      24, or 48 h before centrifugation, and the plasma was stored frozen until
      analysis. All samples were analyzed using an automated electrochemiluminescence
      immunoassay on cobas 6000 e601. The change in ACTH concentration was illustrated
      as ACTH recovery compared to standard conditions defined as samples stored
      immediately on ice, centrifuged and plasma frozen within 1 h. A change in ACTH
      concentration of more than 10% was considered to be of clinical relevance.
      RESULTS: The results showed no clinically relevant change in ACTH recovery for up
      to 4 h compared to standard conditions. For samples stored at room temperature
      for 4 h, a significant (p < .0001) relative mean change in ACTH concentrations of
      -4.3% was observed. CONCLUSION: The comparison between samples stored at room
      temperature for up to 4 h and standard conditions showed that ACTH samples do not
      require cooling until centrifugation, if a mean difference in ACTH concentration
      of -4.3%, between the individual results, can be accepted.

PMID- 27701895
TI  - Speech-language pathology research in the Philippines in retrospect: Perspectives
      from a developing country.
AB  - PURPOSE: There is a need for speech-language pathology (SLP) research in the
      Philippines, in order to fill in knowledge gaps relevant to the local context.
      Information about the local SLP research status remains inadequate. This study
      describes local SLP research done over the almost past four decades. METHOD:
      Using a descriptive retrospective design, a search was made for all empirical
      research articles completed by Filipino SLPs from 1978 to 2015. RESULT: A total
      of 250 research articles were identified and described along several parameters.
      A predominant number were authored by the SLPs in the academe (97.20%). There was
      a focus on language (27.60%) and the nature of communication/swallowing disorders
      (20.80%). More than half utilised quantitative exploratory research designs
      (69.20%). Several used survey forms to generate data (38.41%). Nearly all were
      unpublished (93.60%) and were unfunded (94.80%). CONCLUSION: The current study
      revealed a dearth of research studies, limited diversity of research articles,
      limited research dissemination and funding concerns. It is suggested that the
      results of the current study can serve as a reference point to restructure
      research systems in the Philippines and in other developing countries, and offer
      data that can be used to develop a research agenda for the profession.

PMID- 27701896
TI  - Intraabdominal microdialysis - methodological challenges.
AB  - Microdialysis is used for in vivo sampling of extracellular molecules. The
      technique provides a continuous and dynamic view of concentrations of both
      endogenous released and exogenous administered substances. Microdialysis carries
      a low risk of complications and has proven to be a safe procedure in humans. The
      technique has been applied in several clinical areas, including gastrointestinal
      surgery. Microdialysis may be used for studies of tissue metabolism, and the
      technique is also a promising tool for pharmacological studies of drug
      penetration into abdominal organ tissue and the peritoneal cavity. The clinical
      significance of intraabdominal microdialysis in postoperative monitoring of
      surgical patients has yet to be proven. In this review, we introduce the
      microdialysis technique, and we present an overview of theoretical and practical
      considerations that should be taken into account when using microdialysis in
      intraabdominal clinical research.

PMID- 27701897
TI  - Engineering biosynthesis of high-value compounds in photosynthetic organisms.
AB  - The photosynthetic, autotrophic lifestyle of plants and algae position them as
      ideal platform organisms for sustainable production of biomolecules. However,
      their use in industrial biotechnology is limited in comparison to heterotrophic
      organisms, such as bacteria and yeast. This usage gap is in part due to the
      challenges in generating genetically modified plants and algae and in part due to
      the difficulty in the development of synthetic biology tools for manipulating
      gene expression in these systems. Plant and algal metabolism, pre-installed with
      multiple biosynthetic modules for precursor compounds, bypasses the requirement
      to install these pathways in conventional production organisms, and creates new
      opportunities for the industrial production of complex molecules. This review
      provides a broad overview of the successes, challenges and future prospects for
      genetic engineering in plants and algae for enhanced or de novo production of
      biomolecules. The toolbox of technologies and strategies that have been used to
      engineer metabolism are discussed, and the potential use of engineered plants for
      industrial manufacturing of large quantities of high-value compounds is explored.
      This review also discusses the routes that have been taken to modify the profiles
      of primary metabolites for increasing the nutritional quality of foods as well as
      the production of specialized metabolites, cosmetics, pharmaceuticals and
      industrial chemicals. As the universe of high-value biosynthetic pathways
      continues to expand, and the tools to engineer these pathways continue to
      develop, it is likely plants and algae will become increasingly valuable for the
      biomanufacturing of high-value compounds.

PMID- 27701898
TI  - Differential regulation of oxidative stress and cytokine production by endothelin
      ETA and ETB receptors in superoxide anion-induced inflammation and pain in mice.
AB  - The present study investigated whether endothelin-1 acts via ETA or ETB receptors
      to mediate superoxide anion-induced pain and inflammation. Mice were treated with
      clazosentan (ETA receptor antagonist) or BQ-788 (ETB receptor antagonist) prior
      to stimulation with the superoxide anion donor, KO2. Intraplantar treatment with
      30 nmol of clazosentan or BQ-788 reduced mechanical hyperalgesia (47% and 42%),
      thermal hyperalgesia (68% and 76%), oedema (50% and 30%); myeloperoxidase
      activity (64% and 32%), and overt-pain like behaviours, such as paw flinching
      (42% and 42%) and paw licking (38% and 62%), respectively. Similarly,
      intraperitoneal treatment with 30 nmol of clazosentan or BQ-788 reduced leukocyte
      recruitment to the peritoneal cavity (58% and 32%) and abdominal writhing (81%
      and 77%), respectively. Additionally, intraplantar treatment with clazosentan or
      BQ-788 decreased spinal (45% and 41%) and peripheral (47% and 47%) superoxide
      anion production as well as spinal (47% and 47%) and peripheral (33% and 54%)
      lipid peroxidation, respectively. Intraplantar treatment with clazosentan, but
      not BQ-788, reduced spinal (71%) and peripheral (51%) interleukin-1 beta as well
      as spinal (59%) and peripheral (50%) tumor necrosis factor-alpha production.
      Therefore, the present study unveils the differential mechanisms by which ET-1,
      acting on ETA or ETB receptors, regulates superoxide anion-induced inflammation
      and pain.

PMID- 27701899
TI  - The effect of seasons on Brazilian red propolis and its botanical source:
      chemical composition and antibacterial activity.
AB  - The aim of this study was to evaluate the effect of seasons on the chemical
      composition and antibacterial activity of Brazilian red propolis (BRP) and its
      plant source. BRP was collected from Maceio, Alagoas state, north-east of Brazil,
      during one year. Chemical composition was determined by physicochemical analyses
      and HPLC while antimicrobial activity was assessed against Streptococcus mutans,
      Streptococcus sobrinus, Staphylococcus aureus and Actinomyces naeslundii by
      determining the minimal inhibitory and bactericidal concentrations (MIC and MBC,
      respectively). The comparative chemical profiles varied quantitatively according
      to the collection period. Formononetin was the most abundant compound in both
      propolis and resin, while isoliquiritigenin, (3S)-neovestitol, (3S)-vestitol are
      suggested to be responsible for antimicrobial activity of Brazilian red propolis.
      MIC varied from 15.6 to 125 MUg/mL, whereas MBC varied from 31.2 to 500 MUg/mL.
      Therefore, season in which propolis and its botanical source are collected indeed
      influences their chemical compositions, resulting in variations in their
      antibacterial activity.

PMID- 27701900
TI  - Impaired Upregulation of the Costimulatory Molecules, CD27 and CD28, on CD4+ T
      Cells from HIV Patients Receiving ART Is Associated with Poor Proliferative
      Responses.
AB  - HIV patients beginning antiretroviral therapy (ART) with advanced
      immunodeficiency often retain low CD4+ T cell counts despite virological control.
      We examined proliferative responses and upregulation of costimulatory molecules,
      following anti-CD3 stimulation, in HIV patients with persistent CD4+ T cell
      deficiency on ART. Aviremic HIV patients with nadir CD4+ T cell counts <100
      cells/MUL and who had received ART for a median time of 7 (range 1-11) years were
      categorized into those achieving low (<350 cells/MUL; n = 13) or normal (>500
      cells/MUL; n = 20) CD4+ T cell counts. Ten healthy controls were also recruited.
      CD4+ T cell proliferation (Ki67) and upregulation of costimulatory molecules
      (CD27 and CD28) after anti-CD3 stimulation were assessed by flow cytometry.
      Results were related to proportions of CD4+ T cells expressing markers of T cell
      senescence (CD57), activation (HLA-DR), and apoptotic potential (Fas). Expression
      of CD27 and/or CD28 on uncultured CD4+ T cells was similar in patients with
      normal CD4+ T cell counts and healthy controls, but lower in patients with low
      CD4+ T cell counts. Proportions of CD4+ T cells expressing CD27 and/or CD28
      correlated inversely with CD4+ T cell expression of CD57, HLA-DR, and Fas. After
      anti-CD3 stimulation, induction of CD27hiCD28hi expression was independent of
      CD4+ T cell counts, but lower in HIV patients than in healthy controls. Induction
      of CD27hiCD28hi expression correlated with induction of Ki67 expression in total,
      naive, and CD31+ naive CD4+ T cells from patients. In HIV patients responding to
      ART, impaired induction of CD27 and CD28 on CD4+ T cells after stimulation with
      anti-CD3 is associated with poor proliferative responses as well as greater CD4+
      T cell activation and immunosenescence.

PMID- 27701901
TI  - Increased cognitive problem reporting after information about chemotherapy
      induced cognitive decline: The moderating role of stigma consciousness.
AB  - OBJECTIVE: Information about treatment side effects can increase their
      occurrence; breast cancer (BC) patients showed increased cognitive problem
      reporting (CPR) and decreased memory performance after information about
      cognitive side effects. The current study extends previous research on adverse
      information effects (AIE) by investigating (a) risk factors, (b) underlying
      mechanisms and (c) an intervention to reduce AIE. DESIGN: In an online
      experiment, 175 female BC patients were randomly assigned to one of three
      conditions. In the two experimental groups, patients were informed about the
      possible occurrence of cognitive problems after chemotherapy with (intervention
      group) or without (experimental group) reassuring information that 'there are
      still patients who score well on memory tests'. In the control group, no
      reference to chemotherapy-related cognitive problems was made. MAIN OUTCOME
      MEASURES: Main dependent measure was CPR. Four moderating and five mediating
      processes were examined. RESULTS: CPR increased with higher levels of stigma
      consciousness in the two experimental groups, but not in the no-information
      control group. CONCLUSION: Merely informing patients about cognitive side effects
      may increase their occurrence, especially among individuals vulnerable to patient
      stereotypes. Adding reassuring information is not sufficient to reduce AIE.

PMID- 27701903
TI  - Responses made by late talkers and typically developing toddlers during speech
      assessments.
AB  - PURPOSE: Assessing toddlers' speech is challenging. We explored responses made by
      late talkers and their typically developing peers in structured speech sampling
      contexts and determined if late talker subgroups could be identified. METHOD:
      Twenty-six late talkers and 26 age-matched typically developing toddlers
      participated in an expressive phonology assessment and an elicited non-word
      imitation test. We quantified the breadth of toddler responses used in a subset
      of monosyllabic stimuli from the toddler phonology assessment and in the non-word
      imitation test. Correlational and cluster analyses were conducted. RESULT: There
      were six response types: no response, protoword response, different verbal
      response, correct phoneme, common and uncommon phonological errors. Toddlers' use
      of most of the response types correlated across the two sampling contexts. Use of
      the response types also correlated with several direct and parent-report
      assessments. There were significant group differences in the use of several
      response types in both sampling contexts. Five late talker subgroups were
      identified that presented with differing profiles of responses. CONCLUSION:
      Toddlers respond in a variety of ways during structured speech sampling contexts.
      Responses made by late talkers offer insights about the nature of late talking
      and their heterogeneity. Implications for research and clinical management of
      late talkers are discussed.

PMID- 27701902
TI  - Motivational interviewing or reminders for glaucoma medication adherence: Results
      of a multi-site randomised controlled trial.
AB  - OBJECTIVE: Nonadherence reduces glaucoma treatment efficacy. Motivational
      interviewing (MI) is a well-studied adherence intervention, but has not been
      tested in glaucoma. Reminder interventions also may improve adherence. DESIGN:
      201 patients with glaucoma or ocular hypertension were urn-randomised to receive
      MI delivered by an ophthalmic technician (OT), usual care or a minimal
      behavioural intervention (reminder calls). MAIN OUTCOME MEASURES: Outcomes
      included electronic monitoring with Medication Event Monitoring System (MEMS)
      bottles, two self-report adherence measures, patient satisfaction and clinical
      outcomes. Multilevel modelling was used to test differences in MEMS results by
      group over time; ANCOVA was used to compare groups on other measures. RESULTS:
      Reminder calls increased adherence compared to usual care based on MEMS, p =
      .005, and self-report, p = .04. MI had a nonsignificant effect but produced
      higher satisfaction than reminder calls, p = .007. Treatment fidelity was high on
      most measures, with observable differences in behaviour between groups. All
      groups had high baseline adherence that limited opportunities for change.
      CONCLUSION: Reminder calls, but not MI, led to better adherence than usual care.
      Although a large literature supports MI, reminder calls might be a cost-effective
      intervention for patients with high baseline adherence. Replication is needed
      with less adherent participants.

PMID- 27701905
TI  - Lentivirus-mediated angiopoietin-2 gene silencing decreases TNF-alpha induced
      apoptosis of alveolar epithelium cells.
AB  - OBJECTIVE: To investigate the role of angiopoietin-2 (Ang-2) in tumor necrosis
      factor-alpha (TNF-alpha) induced apoptosis of alveolar epithelium cells (AECs).
      METHODS: TNF-alpha was used to induce human alveolar epithelial HPAEpiC cells,
      and Ang-2 siRNA vector was transfected to the HPAEpiC cells. RT-PCR and Western
      blot were used. TUNEL staining was applied to observe apoptosis, and annexin V
      FITC-PI staining was used to calculate apoptosis rate. RESULTS: mRNA and protein
      expressions of Ang-2, activated Bax, and cleaved caspase-3 in HPAEpiC cells were
      up-regulated, but the expression level of Bcl-2 decreased (P < 0.05). After
      transfection of Ang-2 siRNA, mRNA and protein expressions of Ang-2, activated
      Bax, and cleaved caspase-3 in HPAEpiC cells were down-regulated, but the
      expression level of Bcl-2 increased (P < 0.05). The number of apoptotic cells
      increased after TNF-alpha treatment; however, the number decreased after Ang-2
      siRNA transfection. Annexin V-FITC-PI staining verified that the total number of
      apoptotic cells was elevated with TNF-alpha treatment, but declined after
      transfection of Ang-2 siRNA. CONCLUSIONS: The expression level of Ang-2 increased
      during TNF-alpha-induced apoptosis. Inhibiting Ang-2 expression may suppress the
      early stages of cell apoptosis and the degree of TNF-alpha-induced apoptosis.

PMID- 27701904
TI  - Impedance aggregometric analysis of platelet function of apheresis platelet
      concentrates as a function of storage time.
AB  - Multiple electrode (impedance) aggregometry (MEA) allows reliable monitoring of
      platelet function in whole blood. The aims of the present study were to implement
      MEA for analyzing aggregation in platelet concentrates and to correlate results
      with storage time and blood gas analysis (BGA). We investigated the influence of
      platelet counts, calcium concentrations and agonists on platelet aggregation.
      Samples of apheresis concentrates up to an age of 12 days were investigated by
      MEA and BGA. For ASPI- and TRAPtest MEA was reproducible for a platelet count of
      400 per 10-9 L and a calcium concentration of 5 mmol L-1. Platelets at the age of
      2-4 days yielded steady aggregation. Platelet concentrates exceeding the storage
      time for transfusion showed steady aggregation up to 10 days, but a significant
      decline on day 12. Weak correlation was found regarding pCO2 and MEA as well as
      regarding glucose concentration and MEA. Our results indicate that MEA is
      applicable for evaluation of aggregation in stored apheresis concentrates.
      Prolonged storage seems not to be prejudicial regarding platelet aggregation.
      Platelet concentrates showed acceptable BGA throughout storage time. Further
      studies are required to evaluate the application of MEA for quality controls in
      platelet concentrates.

PMID- 27701906
TI  - ESCRTs and associated proteins in lysosomal fusion with endosomes and
      autophagosomes.
AB  - Endolysosomal and autophagosomal degradation pathways are highly connected at
      various levels, sharing multiple molecular effectors that modulate them
      individually or simultaneously. These two lysosomal degradative pathways are
      primarily involved in the disposal of cargo internalized from the cell surface or
      long-lived proteins or aggregates and aged organelles present in the cytosol.
      Both of these pathways involve a number of carefully regulated vesicular fusion
      events that are dependent on ESCRT proteins. The ESCRT proteins especially ESCRT
      I and III participate in the regulation of fusion events between
      autophagosome/amphisome and lysosome. Along with these, a number of functionally
      diverse ESCRT associated and regulatory proteins such as, endosomal PtdIns (3) P
      5-kinase Fab1, ALIX, mahogunin ring finger 1, atrogin 1, syntaxin 17, ATG12-ATG3
      complex, and protein kinase CK2alpha are involved in fusion events in either or
      both the lysosomal degradative pathways.

PMID- 27701908
TI  - Sub-optimal adherence to combination anti-retroviral therapy and its associated
      factors according to self-report, clinician-recorded and pharmacy-refill
      assessment methods among HIV-infected adults in Addis Ababa.
AB  - Adherence to combination antiretroviral therapy (cART) is generally high in most
      resource-limited settings. However, sub-optimal adherence occurs in a sizable
      proportion of patients, and is independently predictive of detectable viremia. We
      investigated sub-optimal adherence according to self-report, clinician-recorded,
      and pharmacy-refill assessment methods, and their associated factors among HIV
      infected adults receiving cART in Addis Ababa, Ethiopia. Eight-hundred seventy
      patients who initiated cART between May 2009 and April 2012 were randomly
      selected, and 664 patients who were alive, had remained in clinical care and were
      receiving cART for at least six-months were included. Sub-optimal adherence was
      defined as patients' response of less than "all-of the time" to the self-report
      adherence question, or any clinician-recorded poor adherence during the six most
      recent clinic visits, or a pharmacy-refill of <95% medication possession ratio
      (MPR). Logistic regression models were fitted to identify factors associated with
      sub-optimal adherence. The average adherence level to cART, expressed as MPR, was
      nearly 97%. However, sub-optimal adherence occurred in 12%, 4%, and 27% of
      patients according to self-report, clinician-recorded, and pharmacy-refill
      measures, respectively. More satisfaction with social support was significantly
      associated with less sub-optimal adherence according to self-report and clinician
      record. Younger age, lower educational level, and lower CD4 cell count at cART
      initiation were significantly associated with sub-optimal refill-based adherence.
      Findings from our large multi-center study suggest that sub-optimal adherence was
      present in up to a quarter of the patients, despite a high degree of average
      adherence to cART. Interventions aimed at preventing sub-optimal adherence should
      focus on improving social support, on younger patients, on patients with lower
      educational level, and on those who started cART at a lower CD4 cell count.

PMID- 27701907
TI  - Speech and nonspeech: What are we talking about?
AB  - Understanding of the behavioural, cognitive and neural underpinnings of speech
      production is of interest theoretically, and is important for understanding
      disorders of speech production and how to assess and treat such disorders in the
      clinic. This paper addresses two claims about the neuromotor control of speech
      production: (1) speech is subserved by a distinct, specialised motor control
      system and (2) speech is holistic and cannot be decomposed into smaller
      primitives. Both claims have gained traction in recent literature, and are
      central to a task-dependent model of speech motor control. The purpose of this
      paper is to stimulate thinking about speech production, its disorders and the
      clinical implications of these claims. The paper poses several conceptual and
      empirical challenges for these claims - including the critical importance of
      defining speech. The emerging conclusion is that a task-dependent model is called
      into question as its two central claims are founded on ill-defined and
      inconsistently applied concepts. The paper concludes with discussion of
      methodological and clinical implications, including the potential utility of
      diadochokinetic (DDK) tasks in assessment of motor speech disorders and the
      contraindication of nonspeech oral motor exercises to improve speech function.

PMID- 27701909
TI  - Efficacy of an anti-CD22 antibody-monomethyl auristatin E conjugate in a
      preclinical xenograft model of precursor B-cell acute lymphoblastic leukemia.

PMID- 27701911
TI  - Autologous hematopoietic cell transplantation for acute promyelocytic leukemia in
      second complete remission: outcomes before and after the introduction of arsenic
      trioxide.
AB  - We conducted a retrospective registry-based study involving 198 patients with
      acute promyelocytic leukemia (APL) who underwent autologous hematopoietic cell
      transplantation (HCT) during second complete remission (CR2) from 1995 to 2012.
      Arsenic trioxide (ATO) became commercially available in Japan in December 2004,
      and a substantial increase in the annual numbers of transplantations has occurred
      since 2005. Patients transplanted after 2006 had significantly better relapse
      free and overall survival than those transplanted before 2004 (p = .028 and p =
      .027, respectively). There was a significant difference in cumulative incidence
      of relapse in favor of those transplanted after 2006 (p = .008), whereas non
      relapse mortality did not differ between the two groups (p = .683). Our findings
      suggest that the introduction of ATO may have reduced post-transplantation
      relapse without increasing non-relapse mortality, resulting in significant
      improvements in overall outcomes for relapsed APL patients undergoing autologous
      HCT during CR2.

PMID- 27701910
TI  - Impact of ABC single nucleotide polymorphisms upon the efficacy and toxicity of
      induction chemotherapy in acute myeloid leukemia.
AB  - Anthracycline uptake could be affected by efflux pumps of the ABC family. The
      influence of 7 SNPs of ABC genes was evaluated in 225 adult de novo acute myeloid
      leukemia (AML) patients. After multivariate logistic regression there were no
      significant differences in complete remission, though induction death was
      associated to ABCB1 triple variant haplotype (p = .020). The ABCB1 triple variant
      haplotype was related to higher nephrotoxicity (p = .016), as well as this
      haplotype and the variant allele of ABCB1 rs1128503, rs2032582 to hepatotoxicity
      (p = .001; p = .049; p < .001). Furthermore, the variant allele of ABCC1
      rs4148350 was related to severe hepatotoxicity (p = .044), and the variant allele
      of ABCG2 rs2231142 was associated to greater cardiac (p = .004) and lung
      toxicities (p = .038). Delayed time to neutropenia recovery was observed with
      ABCB1 rs2032582 variant (p = .047). This study shows the impact of ABC
      polymorphisms in AML chemotherapy safety. Further prospective studies with larger
      population are needed to validate these associations.

PMID- 27701913
TI  - The first case of acute T-cell lymphoblastic leukemia containing the e19a2 BCR
      ABL1 transcript: a durable molecular response using imatinib-based chemotherapy.

PMID- 27701912
TI  - Impact of metformin on the progression of MGUS to multiple myeloma.

PMID- 27701914
TI  - Fertility knowledge and the timing of first childbearing: a cross-sectional study
      in Japan.
AB  - Although fertility educational initiatives have increased in developed countries
      to prevent infertility and to broaden fertility choices, the relationship between
      knowledge and behaviour is still poorly understood. In order to investigate the
      association between fertility knowledge and timing of childbearing, we
      investigated male and female participants between 35 and 44 years of age who had
      children (n = 640) from an online survey conducted in Japan in 2013. The age at
      which participants actually gave birth to or fathered their first child was
      compared between those who were aware for at least a decade of age-related
      decline in female fertility (hereinafter, those with past fertility knowledge)
      and those without. Age at first birth was significantly younger and more narrowly
      distributed among women with past fertility knowledge than among those without:
      28.2 +/- 3.4 vs. 29.8 +/- 4.6 (mean +/- SD). A multivariate linear regression
      analysis showed that women with past fertility knowledge gave birth to their
      first child 2.34 [95% confidence interval (CI): 1.09-3.59] years earlier compared
      to those without such knowledge. No significant relation existed among men. Being
      informed in young adulthood about the facts of fertility might be related to
      starting a family at an earlier age, although further longitudinal evaluation
      will be necessary.

PMID- 27701915
TI  - Postpartum haemorrhage: prevention and treatment.
AB  - INTRODUCTION: Postpartum hemorrhage (PPH) is one of the leading causes of
      maternal death and severe maternal morbidity worldwide and strategies to prevent
      and treat PPH vary among international authorities. Areas covered: This review
      seeks to provide a global overview of PPH (incidence, causes, risk factors),
      prevention (active management of the third stage of labor and prohemostatic
      agents), treatment (first, second and third-line measures to control PPH), by
      also underlining recommendations elaborated by international authorities and
      using algorithms. Expert commentary: When available, oxytocin is considered the
      drug of first choice for both prevention and treatment of PPH, while peripartum
      hysterectomy remains the ultimate life-saving procedure if pharmacological and
      resuscitation measures fail. Nevertheless, the level of evidence for preventing
      and treating PPH is globally low. The emergency nature of PPH makes randomized
      controlled trials (RCT) logistically difficult. Population-based observational
      studies should be encouraged as they can usefully strengthen the evidence base,
      particularly for components of PPH treatment that are difficult or impossible to
      assess through RCT.

PMID- 27701916
TI  - Biomimetic radical chemistry.

PMID- 27701917
TI  - Sensitivity improvements of a resonance-based tactile sensor.
AB  - Resonance-based contact-impedance measurement refers to the application of
      resonance sensors based on the measurement of the changes in the resonance curve
      of an ultrasonic resonator in contact with a surface. The advantage of the
      resonance sensor is that it is very sensitive to small changes in the contact
      impedance. A sensitive micro tactile sensor (MTS) was developed, which measured
      the elasticity of soft living tissues at the single-cell level. In the present
      paper, we studied the method of improving the touch and stiffness sensitivity of
      the MTS. First, the dependence of touch sensitivity in relation to the resonator
      length was studied by calculating the sensitivity coefficient at each length
      ranging from 9 to 40 mm. The highest touch sensitivity was obtained with a 30-mm
      long glass needle driven at a resonance frequency of 100 kHz. Next, the numerical
      calculation of contact impedance showed that the highest stiffness sensitivity
      was achieved when the driving frequency was 100 kHz and the contact-tip diameter
      of the MTS was 10 MUm. The theoretical model was then confirmed experimentally
      using a phase-locked-loop-based digital feedback oscillation circuit. It was
      found that the developed MTS, whose resonant frequency was 97.030 kHz, performed
      with the highest sensitivity of 53.2 * 106 Hz/N at the driving frequency of
      97.986 kHz, i.e. the highest sensitivity was achieved at 956 Hz above the
      resonant frequency.

PMID- 27701918
TI  - Radiofrequency ablation combined with percutaneous ethanol injection for
      hepatocellular carcinoma: a systematic review and meta-analysis.
AB  - BACKGROUND: Radiofrequency ablation (RFA) and percutaneous ethanol injection
      (PEI) are important treatments for patients with hepatocellular carcinoma (HCC)
      who are not eligible for resection and liver transplantation. Therefore, it is
      important to establish comparisons between RFA, PEI and the two therapies in
      combination. AIMS: To evaluate the clinical efficacy and safety of combined RFA
      PEI versus monotherapy with either RFA or PEI for HCC to provide references for
      clinical practice and further research. METHODS: We searched all eligible studies
      published before September 2015 in the Cochrane Library, PubMed, Embase, Web of
      Science and Chinese databases, such as CBM, CNKI, VIP and WanFang and also
      retrieved papers from other sources. All relevant controlled trials were
      collected. Meta-analyses were performed using RevMan version 5.3 software (The
      Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark).
      RESULTS: Thirteen trials with 1621 patients were identified. Compared with PEI,
      RFA was associated with significant improvement in overall survival (OS) rate at
      1, 2, 3 and 4 years, cancer-free survival (CFS) rate at 1, 2 and 3 years and
      complete tumour necrosis. RFA was associated with a significant reduction in the
      local recurrence rate at 1, 2 and 3 years. However, RFA was also associated with
      a higher total risk of complications. Compared with RFA alone, combined RFA-PEI
      was associated with a significant improvement in the OS rate at 1.5, 2 and 3
      years and a significant reduction in the local recurrence rate. However, combined
      RFA-PEI was also associated with a higher risk of fever. CONCLUSION: The
      combination of RFA and PEI appears to be the optimal treatment strategy when
      considering combined RFA-PEI or either RFA or PEI alone. Combined RFA-PEI
      significantly improves OS and reduces the risk of local recurrence without
      increasing major complications. Further large-scale studies are needed to assess
      economic outcomes and quality of life.

PMID- 27701919
TI  - Caring for juveniles with mental disorders in adult corrections facilities.
AB  - Although juveniles have developmental, educational, healthcare, and
      rehabilitation needs that differ from adults, thousands of them have been
      confined in adult corrections facilities in the past 30 years. This manuscript
      will review how and why juveniles end up in adult corrections facilities, who
      they are, their rehabilitative needs, and how they differ from adults in
      corrections facilities and youths in the juvenile justice system. The importance
      of providing developmentally-informed mental health services to youths in adult
      corrections facilities is examined, along with barriers to traditional adolescent
      psychiatric practice. Recommendations for future directions in adolescent
      psychiatric care are presented.

PMID- 27701920
TI  - Status and advancement of microwave ablation in China.
AB  - Tumour ablation is defined as the direct application of chemical or thermal
      therapy to eradicate or substantially destroy a tumour. Currently, minimally
      invasive ablation techniques are available for the local destruction of focal
      tumours in multiple organ sites. Microwave ablation (MWA) is premised on the
      biological response of solid tumours to tissue hyperthermia, and it is a
      relatively low-risk procedure. Due to several advantages of MWA, including higher
      thermal efficiency, higher capability for coagulating blood vessels, faster
      ablation time and the simultaneous application of multiple antennae, MWA could be
      a promising minimally invasive ablation technique for the treatment of solid
      tumours. Therefore, the use of MWA has developed rapidly in China during the last
      decade. Many successful studies have been performed, and widespread use has been
      achieved for multiple types of tumours in China, especially for liver cancer.
      This review will describe the state-of-the-art of MWA in China, including the
      development of MWA equipment and its application in the treatment of multiple
      types of tumours.

PMID- 27701921
TI  - Cost-effectiveness of intravitreal aflibercept versus other treatments for wet
      age-related macular degeneration in Japan.
AB  - OBJECTIVE: This analysis estimated the cost-effectiveness of intravitreal
      aflibercept injection(s) (IAI) for wet age-related macular degeneration (wAMD)
      compared with other treatments in Japan. METHODS: This was a cost-utility
      analysis based on published data. A state-transition cohort model was constructed
      with six health states based on best-corrected visual acuity in the better-seeing
      eye. The cycle time was 4 weeks, and the time horizon was 12 years. The model
      compared IAI 2 mg every 8 weeks (2q8) for 2 years after three initial monthly
      injections, ranibizumab as needed, ranibizumab 0.5 mg every 4 weeks (0.5q4),
      pegaptanib sodium 0.3 mg every 6 weeks, verteporfin photodynamic therapy (PDT),
      and best supportive care, assumed to include medical management and monitoring,
      but no active therapy. Costs (expressed as Japanese yen [JPY]) and quality
      adjusted life years (QALYs) gained were estimated for each treatment and
      discounted at 2.0%. Input data were obtained from clinical studies, the Japanese
      drug tariff and social insurance reimbursement schedule, and expert opinion. The
      analysis was conducted from the societal perspective, including medical costs as
      well as costs of blindness. RESULTS: IAI 2q8 was dominant (i.e. more effective in
      terms of QALYs and less costly) to all other comparators (ranibizumab as needed,
      ranibizumab 0.5q4, pegaptanib sodium, PDT, and best supportive care), as shown by
      the incremental cost-utility ratio (i.e. cost per QALY gained). LIMITATIONS: The
      strengths of the analysis include the wide range of comparators evaluated and the
      use of Japanese-specific utility data. The limitations include the use of one
      eye, inclusion of published data up to 2 years only, and assumptions on disease
      course over 5 years. CONCLUSIONS: IAI 2q8 was more effective in terms of QALYs
      and less costly compared with other treatments for wAMD in Japan.

PMID- 27701922
TI  - Myeloperoxidase deficiency enhances zymosan phagocytosis associated with up
      regulation of surface expression of CD11b in mouse neutrophils.
AB  - Myeloperoxidase (MPO), a major component of neutrophils, catalyzes the production
      of hypochlorous acid (HOCl) from hydrogen peroxide and chloride anion.
      Phagocytosis is a critical event induced by neutrophils for host defense and
      inflammation. Interestingly, we found that MPO-deficient (MPO-/-) neutrophils
      engulfed larger amounts of zymosan than wild-type neutrophils. Blocking of the
      CD11b subunit of complement receptor 3 (CR3) as well as inhibition of focal
      adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK)
      dramatically reduced zymosan phagocytosis. In contrast, blocking of dectin-1,
      toll-like receptor 2 (TLR2), or spleen tyrosine kinase (Syk) had no significant
      effects on phagocytosis. Western blotting analysis showed that inhibition of FAK
      decreased the phosphorylation of ERK1/2, indicating that ERK1/2 is a downstream
      regulator of FAK in neutrophils. Importantly, we found that cell surface
      expression of CD11b and phosphorylation of ERK1/2 was significantly higher in
      zymosan-stimulated MPO-/- neutrophils than in zymosan-stimulated wild-type
      neutrophils. Pretreatment with the MPO inhibitor 4-aminobenzoic acid hydrazide
      dramatically enhanced both zymosan phagocytosis and the surface expression of
      CD11b in wild-type neutrophils, but not in MPO-/- neutrophils. Collectively,
      these results strongly suggest that up-regulation of the CD11b/FAK/ERK signaling
      pathway due to absence of MPO enhances the zymosan phagocytic activity of mouse
      neutrophils.

PMID- 27701923
TI  - Benign thyroid nodules treatment using percutaneous laser ablation (PLA) and
      radiofrequency ablation (RFA).
AB  - PURPOSE: To evaluate the reduction over time of benign thyroid nodules treated
      using percutaneous laser ablation (PLA) and radiofrequency ablation (RFA) by the
      same equipe. MATERIALS AND METHODS: Ninety patients (age 55.6 +/- 14.1 years)
      underwent ablation for benign thyroid nodule causing compression/aesthetic
      dissatisfaction from 2011. Fifty-nine (age 55.8 +/- 14.1 years) underwent RFA and
      31 (age 55.2 +/- 14.2 years) PLA, ultrasound guided. Technical success,
      complications, duration of ablation and treatment, energy deployed, volumetric
      percentage reduction at 1, 6 and 12 months were derived. A regression model for
      longitudinal measurements was used with random intercept and random slope. Values
      are expressed as mean +/- standard deviation or N (%). RESULTS: Technical success
      was always obtained. No major complications occurred. Mean ablation time was 30.1
      +/- 13.8 vs. 13.9 +/- 5.9 min (p < .0001) and mean energy deployment was 5422.3
      +/- 2484.5 J vs. 34 662.7 +/- 15 812.3 J in PLA vs. RFA group. Mean volume
      reduced from 20.3 +/- 16.4 ml to 13.17 +/- 10.74 ml (42% +/- 17% reduction) at
      1st month, 8.7 +/- 7.4 ml (60% +/- 15% reduction) at 6th month and 7.1 +/- 7.7 ml
      (70%% +/- 16% reduction) at 12th month, in PLA group, and from 32.7 +/- 19.5 ml
      to 17.2 +/- 12.9 ml (51%+/-15% reduction) at 1st month, 12.8 +/- 9.6 ml (64 +/-
      14% reduction) at 6th month and 9.9 +/- 9.2 ml (74% +/- 14% reduction) at 12th
      month in RFA group. No difference in time course of the relative volume reduction
      between the two techniques was found. CONCLUSIONS: RFA and PLA are similarly
      feasible, safe and effective in treating benign thyroid nodules when performed by
      the same equipe. RFA is faster than PLA but require significantly higher energy.

PMID- 27701924
TI  - Targeting factors for change: contraceptive counselling and care of female
      adolescents.
AB  - INTRODUCTION: Sexual and reproductive health care should empower and enable all
      individuals to have a sex life that is as safe and pleasurable as possible.
      Achievement of this goal for adolescents is often impeded by regional and
      sociocultural barriers. OBJECTIVES: To review global barriers to provision of
      effective counselling and care of adolescents seeking advice on contraception and
      sexual and reproductive health and identify elements of best practice that can be
      adapted to meet their needs at regional level. METHODS: Experts with clinical
      experience and a scholarly background in the provision of contraceptive services
      to adolescents participated in a stepwise process of literature review and
      discussion according to the agreed objectives. RESULTS: The Global CARE
      (Contraception: Access, Resources, Education) group identified barriers to the
      access, availability and acceptance of contraception by adolescents, not only at
      the political and sociocultural level but also within health care practice. The
      group collected and summarized successful local strategies and tools suitable for
      adaptation in other regions. Elements of best practice for providing
      contraception regardless of setting or regional constraints, including required
      skills, knowledge, and attitudes, were also proposed. CONCLUSION: Sharing of
      evidence-based best practice in delivering contraceptive services, improvements
      in health care provider education, and sharing of experience between countries
      will hopefully help to overcome the barriers to appropriate and effective
      counselling and care of adolescents.

PMID- 27701925
TI  - Diet and asthma: need to account for asthma type and level of prevention.

PMID- 27701926
TI  - Twenty-five years of the international Bled course for teachers of family
      medicine in Europe: Glancing back and looking forward.
AB  - The international Bled course for teacher training has played a central role in
      faculty development in family medicine for the past 25 years. The course was
      originally designed to promote faculty development for family medicine teachers
      in the new academic discipline of family medicine in Slovenia in 1990 and to
      introduce new topics into the family medicine curriculum. In this background
      paper, we perform a SCOT analysis (strengths, challenges, opportunities, and
      threats) of the current course, evaluating participant feedback and reviewing
      past topics and their impact on local and international teaching programmes. We
      also review the place of the course in the context of other teacher-training
      programmes in family medicine in Europe. We found that the structure and learning
      aims of the Bled course have remained stable over 25 years. It provides a safe,
      well-structured learning environment for the participants even though the course
      topic is different every year. The course has had a significant impact on
      curriculum development and teacher training in Slovenia as well as in many other
      countries in Europe and beyond. Because of the positive impact of the course and
      the high degree of satisfaction of the participants and course directors, it
      seems worthwhile to continue this endeavour. New directions for the course will
      depend on the learning needs of the participants and the evolving medical
      curricula in the countries they represent.

PMID- 27701927
TI  - Chlamydia screening and prophylactic treatment in termination of pregnancy
      clinics in the Netherlands and Great Britain: a qualitative study.
AB  - BACKGROUND: Women having a termination of pregnancy (TOP) have higher rates of
      Chlamydia trachomatis (CT) than the general population. In this study, we
      explored CT treatment and prevention in Dutch TOP clinics in comparison to that
      provided in Great Britain (GB). METHODS: A qualitative study including 14 semi
      structured interviews with health care professionals (HCPs) in TOP clinics (the
      Netherlands: 9, GB: 5). Interviews were recorded, transcribed, and analysed by
      thematic content analysis. RESULTS: Prophylactic treatment with azithromycin is
      routinely prescribed after surgical TOP, but not after medical TOP ('abortion
      pill'). Sexually transmitted infections (STI) tests are offered to clients who
      are considered at high risk of having STI. Uptake varies according to health
      insurance coverage of STI testing. Some Dutch clinics are able to provide free
      testing for women under 25 years of age. Sexual health counselling is often
      limited to discussing birth control. The major difference between the Netherlands
      and GB is that GB TOP clinics more often offer free STI testing and prophylaxis
      to their clients. CONCLUSION: HCPs in Dutch TOP clinics consider STI testing an
      important part of their service, but financial barriers prevent testing on
      location. Dutch TOP clinics should offer STI tests to all women, and
      collaboration with public health services could improve STI testing and
      counselling for young people. Furthermore, clinics should treat all TOP clients
      with prophylactic azithromycin. This could prevent CT and other upper genital
      tract post-abortion infections.

PMID- 27701928
TI  - Pica as a manifestation of iron deficiency.
AB  - INTRODUCTION: Pica is the compulsive eating of non-nutritive substances. It is
      often associated with iron deficiency but its pathophysiology is unknown. Areas
      covered: We searched the literature using the keywords listed below. Our aim was
      to describe the phenomenon in its various aspects, to touch briefly on the
      historical and cultural background, and to examine in more detail the studies
      that tried to analyze the relative roles of iron deficiency and pica. Expert
      commentary: Pica is an intriguing symptom known for centuries. Pregnant women and
      preadolescents are at the highest risk of pica. Iron absorption is reduced in the
      presence of non-nutritive substances. Iron therapy usually cures the pica
      behavior. There are different forms of pica, one caused directly by iron
      deficiency probably due to the lack of iron in some areas of the brain and one
      more culturally driven and including mostly geophagy.

PMID- 27701929
TI  - Evaluation of the Cytotoxic Effects of Hyperthermia and 5-Fluorouracil Loaded
      Magnetic Nanoparticles on Human Colon Cancer Cell Line HT-29.
AB  - The purpose of this study was to evaluate the combined effects of heat and poly
      lactic-co-glycolic acid (PLGA) nanoparticles, as 5-fluorouracil carriers
      with/without iron oxide core, on the viability and proliferation capacity of
      human colon cancer cell line HT-29 in the spheroid model. HT-29 spheroid cells
      were treated with different concentrations of 5-FU or 5-FU loaded into both
      nanoparticles for 74 h. Hyperthermia was then performed at 43 degrees C for 60
      min. Finally, the effects of the mentioned treatments on cell viability and
      proliferation capacity were evaluated using the trypan blue dye exclusion test
      and colony formation assay, respectively. Our results showed that hyperthermia,
      in combination with 5-FU or PLGA nanoparticles as 5-FU carriers, significantly
      enhanced the cytotoxic effects as compared to the control group. Considering that
      nanoparticles could increase the intracellular concentration of drugs in cancer
      cells, the extent of cytotoxic effects following treatment with 5-FU loaded into
      both nanoparticles was significantly higher than that with free 5-FU. In
      addition, the presence of iron oxide cores in nanoparticles during hyperthermia
      enhanced the cytotoxic effects of hyperthermia compared with nanoparticles
      without iron oxide core. Based on this study, hyperthermia in combination with 5
      FU-loaded PLGA nanoparticles with iron oxide core drastically reduced the
      proliferation capacity of HT-29 cells; therefore, it may be considered a new
      direction in the treatment of colon cancer.

PMID- 27701932
TI  - Introduction.

PMID- 27701930
TI  - Prasugrel hydrochloride for the treatment of acute coronary syndrome patients.
AB  - INTRODUCTION: Dual antiplatelet therapy (DAPT) with aspirin combined with either
      a thienopyridine (clopidogrel or prasugrel) or acyclopentyl-triazolo-pyrimidine
      (ticagrelor) plays a vital role in the management of acute coronary syndrome
      (ACS) especially in those undergoing percutaneous coronary intervention (PCI) but
      even those being managed medically. Observational studies and some formal studies
      have shown patients on the standard dual antiplatelet regimen (clopidogrel and
      aspirin) continue to have further ischemic events and can suffer stent
      thrombosis. It has been demonstrated that clopidogrel is associated with a
      delayed onset of action with a considerable inter-individual variation to
      treatment thus making it difficult to achieve an optimal level of platelet
      inhibition. Areas covered: This article will review the current evidence that is
      available regarding the effectiveness and safety of prasugrel in ACS patients
      undergoing percutaneous coronary intervention (PCI). Expert commentary: Prasugrel
      is an oral third-generation inhibitor of platelet activation and aggregation.
      Laboratory studies and early phase clinical trials show prasugrel has a faster
      onset of action, is more potent and has reduced inter-patient response
      variability compared to clopidogrel. The published studies so far demonstrated
      that prasugrel when compared to clopidogrel also shows a higher degree of
      effectiveness in the prevention of platelet-initiated thrombotic events in
      patients with ACS undergoing PCI, however these benefits are offset somewhat by
      an increased bleeding risk.

PMID- 27701933
TI  - Technical interventions to increase adenoma detection rate in colonoscopy.
AB  - INTRODUCTION: Adenoma detection rate (ADR) is the most robust colonoscopy quality
      metric and clinical studies have adopted it as the ideal method to assess the
      impact of technical interventions. Areas covered: We reviewed papers focusing on
      the impact of colonoscopy technical issues on ADR, including withdrawal time and
      technique, second evaluation of the right colon, patient positional changes,
      gastrointestinal assistant participation during colonoscopy, water-aided
      technique, optimization of bowel preparation and antispasmodic administration.
      Expert commentary: Overall, technical interventions are inexpensive, available
      worldwide and easy to implement. Some of them, such as the adoption of split dose
      regimen and slow scope withdrawal to allow a careful inspection, have been
      demonstrated to significantly improve ADR. Emerging data support the use of water
      exchange colonoscopy. According to published studies, other technical
      interventions seem to provide only marginal benefit to ADR. Unfortunately, the
      available evidence has methodological limitations, such as small sample sizes,
      the inclusion of expert endoscopists only and the evaluation of single technical
      interventions. Additionally, larger studies are needed to clarify whether these
      interventions might have a higher benefit on low adenoma detectors and whether
      the implementation of a bundle of them, instead of a single technical maneuver,
      might have a greater impact on ADR.

PMID- 27701934
TI  - Impact of EMPA-REG OUTCOME(r) on the management of type 2 diabetes mellitus: a
      review for primary care physicians.
AB  - Cardiovascular (CV) disease is the leading cause of death in patients with type 2
      diabetes mellitus (T2DM). Most published trials of glucose-lowering agents have
      shown no significant CV benefit or increased risk of death or heart failure, with
      the exception of metformin. Three novel classes of glucose-lowering agents,
      dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1)
      receptor agonists, and sodium glucose cotransporter 2 (SGLT2) inhibitors, have
      been approved by the U.S. Food and Drug Administration for the treatment of T2DM
      in the United States and have also been available in other parts of the world in
      the past decade. Of the SGLT2 inhibitors, empagliflozin has demonstrated a CV
      benefit in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2
      Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME(r)) while
      trials with other SGLT2 inhibitors are still ongoing. Empagliflozin has also
      provided possible renal protective benefit in those with mild-to-moderate renal
      impairment. The mechanisms behind the benefits seen with empagliflozin are likely
      multifactorial. Empagliflozin is the reasonable choice for add-on therapy in
      patients with long-standing T2DM who are at high CV risk as demonstrated in the
      EMPA-REG OUTCOME(r) study.

PMID- 27701935
TI  - Surrogate markers of visceral fat and response to anti-depressive treatment in
      patients with major depressive disorder: a prospective exploratory analysis.
AB  - BACKGROUND: Body mass index (BMI) and body weight have been shown to be
      associated to treatment outcome in patients with major depressive disorder, but
      this relationship is not clear. Visceral fat might be an underlying mechanism
      explaining this relationship. AIMS: The aim of this study was to prospectively
      investigate whether visceral fat, as measured by hip-to-waist ratio and waist
      circumference, affects treatment outcome in patients with major depressive
      disorder in patients attending a hospital psychiatric care unit in Denmark.
      METHODS: The study was conducted as an observational prospective study including
      33 patients with major depressive disorder. Assessments were made at enrolment
      and after 8 weeks. Primary variables were hip-to-waist ratio and waist
      circumference. Outcome were remission or response of depressive symptoms measured
      with the Hamilton Depression Rating Scale (HAM-D17) interviews and HAM-D6 self
      rating questionnaires. RESULTS: No differences were found in outcome between
      groups of patients with high vs low visceral fat in this population. CONCLUSIONS:
      The lack of association was evident for all surrogate markers of visceral fat,
      and suggests that visceral fat has no impact on outcomes of depressive symptoms.
      However, study limitations might have contributed to this lack of association,
      especially sample size and considerable variations on multiple parameters
      including treatment received during the 8 weeks of follow-up.

PMID- 27701936
TI  - Opioid and amphetamine dependence is associated with methicillin-resistant
      Staphylococcus aureus (MRSA): An epidemiological register study with 73,201
      Swedish in- and outpatients 1997-2013.
AB  - BACKGROUND: While methicillin-resistant Staphylococcus aureus (MRSA) is
      increasing in prevalence globally, Sweden is still a low-prevalence country
      enabling studies on the natural MRSA spread in subpopulations unaffected by a
      surrounding highly infected population. Substance dependence and injection drug
      use have been risk factors for MRSA carriage and infection in other countries. In
      this retrospective, longitudinal register study, we investigated MRSA
      epidemiology 1997-2013 in opioid and amphetamine-dependent individuals, in
      comparison with alcohol-dependent subjects. METHODS: Data from the national
      Swedish in- and outpatients registers included 73,201 individuals from 1997,
      1999, 2004, 2009 and 2013. We analyzed substance use disorder and demographic
      predictors for MRSA using generalized estimating equations. RESULTS: The main
      finding was that both opioid (adjusted odds ratio [AOR] = 2.82; 95% confidence
      interval [CI] = 2.16, 3.67) and amphetamine dependence (AOR = 2.71; 95% CI =
      1.70, 4.16) were significantly associated with MRSA diagnosis compared with
      alcohol dependence, when adjusting for age, sex and year. CONCLUSIONS: These
      findings are of value to understand the dynamics of MRSA epidemiology among
      substance dependent persons with presumably low socioeconomic status and
      potential injection drug use, and implicate repeated surveillance of MRSA among
      these patients.

PMID- 27701937
TI  - Impact of cognitive impairment, depression, disease activity, and disease damage
      on quality of life in women with systemic lupus erythematosus.
AB  - OBJECTIVES: To define the relative role of cognitive impairment, depression,
      disease activity, and disease damage in the decreased health-related quality of
      life (HRQoL) frequently observed in systemic lupus erythematosus (SLE) patients.
      METHOD: We studied 101 Chilean female SLE patients and applied the 12-item
      Medical Outcomes Study (MOS) Short Form Health Survey version 2 (SF-12v2) to
      assess HRQoL and the Cambridge Neuropsychological Test Automated Battery (CANTAB)
      to assess cognitive function. Analysis of covariance (ANCOVA) models included
      demographic and disease-related factors and cognitive function tests of sustained
      attention, memory, and executive function. RESULTS: All measures of HRQoL were
      lower in the 101 female SLE patients compared to the women from the Chilean
      general population. HRQoL was associated with the following factors: (i)
      depression symptoms, which were detrimental to all components of the physical and
      mental HRQoL scores; (ii) executive dysfunction (spatial planning), which was
      associated with lower scores on role limitations due to physical health problems
      and emotional problems, and general health perceptions; (iii) higher activity and
      organ damage were deleterious to role physical, bodily pain, and physical summary
      scores; and (iv) higher damage also impacted physical function. Impairments in
      sustained attention and memory did not decrease the HRQoL. CONCLUSIONS: Our
      results highlight the relevance of executive dysfunction to poor physical and
      mental health components of HRQoL in SLE together with depression, while disease
      activity and disease damage are associated with lower HRQoL physical components.
      The need for cognitive function evaluation and rehabilitation in SLE is
      indicated.

PMID- 27701952
TI  - Add-on mirtazapine improves orgasmic functioning in patients with schizophrenia
      treated with first-generation antipsychotics.
AB  - AIM: Sexual dysfunction, common in schizophrenia, may be further exaggerated by
      antipsychotics, especially those of First Generation (FGAs), and antidepressants,
      such as Selective Serotonin Reuptake Inhibitors (SSRs). Mirtazapine, an
      antidepressant characterized by its different action mechanism compared with that
      of the majority of other antidepressants, may improve SSRI-induced sexual
      dysfunction in patients with depression. It is unknown, however, whether
      mirtazapine improves sexual functioning in schizophrenia. METHODS: This study
      randomly assigned FGA-treated patients with schizophrenia to receive either an
      add-on mirtazapine (n = 20) or a placebo (n = 19) for 6 weeks. Sexual functioning
      was prospectively measured using five relevant items from the Udvalg for Kliniske
      Undersogelser side-effect rating scale (UKU-SERS). RESULTS: Orgasmic function
      improved with statistical significance in the mirtazapine group (p = .03), with
      no changes in any other sexual functions in either group. CONCLUSION: Add-on
      mirtazapine appears to relieve orgasmic dysfunction in FGA-treated patients with
      schizophrenia.

PMID- 27701965
TI  - Saksenaea erythrospora, an emerging mucoralean fungus causing severe necrotizing
      skin and soft tissue infections - a study from a tertiary care hospital in north
      India.
AB  - BACKGROUND: Saksenaea erythrospora is an emerging and recently described
      pathogenic fungus mainly causing invasive cutaneous infections. Globally, very
      few human cases, caused by S. erythrospora, have been reported. In India, among
      the genus Saksenaea, S. vasiformis was the only reported pathogenic species,
      until recently when a case of fungal rhinosinusitis was reported to be caused by
      S. erythrospora. We observed five human cases of necrotizing skin and soft tissue
      infections caused by S. erythrospora following traumatic implantation over 1-year
      study period. METHODS: The study was conducted for a year observing the causative
      role of Saksenaea species in primary cutaneous necrotizing infections. The
      clinical entities were diagnosed by both microbiological and histopathological
      examination of the skin biopsies. The final identification of fungal strains was
      done by comparing internal transcribed spacer (ITS) and D1-D2 domains of the LSU
      (larger subunit) of the nuclear ribosomal RNA (rRNA) sequences with those of type
      strains of the different species of Saksenaea. RESULTS: Out of total 23 cases of
      necrotizing skin and soft tissue infections, 5 were caused by S. erythrospora.
      Intramuscular injection into the gluteal region was the predisposing factor in
      four patients, while upper limb involvement, following medicated adhesive tape
      application, was seen in one patient. All patients were treated with liposomal
      amphotericin B (LAMB) along with extensive debridement of necrotic tissues. Four
      patients responded well however one died. CONCLUSION: Saksenaea erythrospora is
      an emerging mucoralean fungus isolated in India among patients undergoing
      inadvertent I/M injections entailing necrotizing fasciitis at the local site.

PMID- 27701966
TI  - Speech recognition outcomes in Mandarin-speaking cochlear implant users with fine
      structure processing.
AB  - CONCLUSION: Mandarin-speaking adults can use the Fine Structure Processing (FSP)
      coding strategy as well as the Continuous Interleaved Sampling (CIS+) coding
      strategy. No loss in performance was observed after switch-over. Tone
      identification improves over time with the FSP coding strategy, which is of
      benefit to tonal-language users. After some time, fine structure was preferred.
      OBJECTIVE: This study aimed to determine speech perception, tone perception, and
      the subjective preferences of Mandarin-speaking adults who received the FSP
      coding strategy, at upgrade from the CIS + coding strategy. METHODS: Thirteen
      Mandarin-speaking subjects were tested at switch-over from CIS + to the FSP
      coding strategy ~1-month after switch-over, 2-months after switch-over, and 3
      months after switch-over with the Mandarin Hearing in Noise Test (M-HINT), the
      Mandarin Tone Identification in Noise Test (M-TINT), and a visual analogue scale
      assessing Sound and Speech Assessment (SSA). RESULTS: There were no significant
      differences in the M-HINT between presentation levels (62 dB SPL vs 65 dB SPL),
      over time, nor when compared to the CIS + coding strategy. Tone perception
      improved significantly over time with the FSP coding strategy. Subjects rated the
      FSP coding strategy with the OPUS 2 as significantly more 'full' and 'rich' than
      with the CIS + coding strategy after 3-months.

PMID- 27701967
TI  - Wearable Technology for Athletes: Information Overload and Pseudoscience?

PMID- 27701968
TI  - A Systematic Review of Submaximal Cycle Tests to Predict, Monitor, and Optimize
      Cycling Performance.
AB  - Finding the optimal balance between high training loads and recovery is a
      constant challenge for cyclists and their coaches. Monitoring improvements in
      performance and levels of fatigue is recommended to correctly adjust training to
      ensure optimal adaptation. However, many performance tests require a maximal or
      exhaustive effort, which reduces their real-world application. The purpose of
      this review was to investigate the development and use of submaximal cycling
      tests that can be used to predict and monitor cycling performance and training
      status. Twelve studies met the inclusion criteria, and 3 separate submaximal
      cycling tests were identified from within those 12. Submaximal variables
      including gross mechanical efficiency, oxygen uptake (VO2), heart rate, lactate,
      predicted time to exhaustion (pTE), rating of perceived exertion (RPE), power
      output, and heart-rate recovery (HRR) were the components of the 3 tests. pTE,
      submaximal power output, RPE, and HRR appear to have the most value for
      monitoring improvements in performance and indicate a state of fatigue. This
      literature review shows that several submaximal cycle tests have been developed
      over the last decade with the aim to predict, monitor, and optimize cycling
      performance. To be able to conduct a submaximal test on a regular basis, the test
      needs to be short in duration and as noninvasive as possible. In addition, a test
      should capture multiple variables and use multivariate analyses to interpret the
      submaximal outcomes correctly and alter training prescription if needed.

PMID- 27701969
TI  - State of the Science-Ultraendurance Sports.
AB  - Participation in ultraendurance sports has been increasing in recent years. This
      participation growth has been associated with an increase in research focused on
      such events. While the total amount of research related to these sports remains
      relatively small compared with other sports, the research growth is encouraging.
      New sources for research funding for ultraendurance sports should advance the
      science. In addition to continued opportunities with observational studies,
      promising areas of investigation remain for experimental studies and research
      that uses ultraendurance-sport environments as models for studies relevant to
      wider populations. Insight into the breadth of research opportunities in
      ultraendurance sports can be gained by reviewing the abstracts published online
      in the International Journal of Sports Physiology and Performance from the annual
      Medicine & Science in Ultra-Endurance Sports Conference that took place this year
      in Chamonix, France.

PMID- 27701984
TI  - Erratum.

PMID- 27701970
TI  - Sleep and quality of life in people with ileal conduit.
AB  - OBJECTIVE: The aim of this study was to determine the sleep quality and the
      association between sleep quality and quality of life in people with ileal
      conduit. MATERIALS AND METHODS: A descriptive and cross-sectional design was
      adopted. The study sample comprised 111 people with ileal conduit operated on in
      urology clinics in a state hospital between January 2011 and May 2014. Six months
      after the operation, they were called by telephone to participate in the study.
      Data for the study were collected using a questionnaire form, the Pittsburgh
      Sleep Quality Index (PSQI) and the Stoma Quality of Life Scale (SQLS). RESULTS:
      The mean +/- SD total PSQI score of the people with ileal conduit was 10.20 +/-
      2.95, mean total score of SQLS was 43.63 +/- 7.21, mean Work/Social Function
      domain score was 37.27 +/- 5.80 and mean Stoma Function domain score was 50.0 +/-
      12.56. The total sleep quality had a low degree of negative correlation with
      total SQLS score, a medium degree of negative correlation with Work/Social
      Function (r = -0.327, p < .001) and no correlation with Stoma Function (r = 
      0.096, p > .001). People using a night drainage system had higher sleep quality.
      CONCLUSIONS: This study determined that quality of life and sleep deteriorate in
      people with ileal conduit. The quality of life decreases when the sleep quality
      is poor, and decreased quality of life affects quality of sleep in people with
      ileal conduit.

PMID- 27701985
TI  - Micro/nanoencapsulation of essential oils and fragrances: Focus on perfumed,
      antimicrobial, mosquito-repellent and medical textiles.
AB  - Herbal products have been widely used due to good antimicrobial, fragrance and
      medical properties. Essential oils and fragrances can be applied on the textile
      substrates as micro/nanocapsules to prolong lifetime by controlling the release
      rate. The present review tries to give a general overview on the application of
      micro/nanoencapsulated essential oils on the textile substrates to achieve
      aromatherapy textiles. These are divided into four diverse categories as the
      following: antimicrobial, perfumed, mosquito-repellent and medical textiles. The
      reports in this field revealed that the encapsulation technique plays an
      important role in the finishing of plant extracts on the textile substrates. It
      is also anticipated that aromatherapy textiles have to be developed in the new
      fields such as multifunctional textiles having wound-healing, antimicrobial and
      fragrant properties.

PMID- 27701986
TI  - Predictive validity of the ACC/AHA pooled cohort equations in predicting residual
      specific mortality in a national prospective cohort study of adults in the United
      States.
AB  - OBJECTIVE: The predictive validity of the Pooled Cohort risk (PCR) equations for
      residual-specific mortality (deaths not resulting from the 9 leading causes of
      death) among a national sample of U.S. adults has not previously been evaluated,
      which was the purpose of this study. METHODS: Data from the 1999-2010 National
      Health and Nutrition Examination Survey were used, with participants followed up
      through 31 December 2011 to ascertain mortality status. The analyzed sample
      included 11,171 cardiovascular disease-free adults (40-79 years of age). The 10
      year risk of a first atherosclerotic cardiovascular disease (ASCVD) event was
      determined from the PCR equations. RESULTS: For the entire sample, 849,202 person
      months occurred with an incidence rate of 0.29 (95% CI: 0.25-0.33) residual
      specific deaths per 1,000 person-months. The unweighted median follow-up duration
      was 72 months. For all analyses, ASCVD risk score (via the PCR equations) was
      significantly associated with residual-specific mortality. In a fully adjusted
      model including moderate-to-vigorous physical activity (MVPA), obesity, age (yrs;
      continuous measure), gender (male/female) and race-ethnicity (Mexican American,
      non-Hispanic white, non-Hispanic black and other) as covariates, those with an
      ASCVD >= 20 (vs. < 20) had a 91% increased hazard of residual-specific death
      during the follow-up period (HR = 1.91; 95% CI: 1.10-3.31). Expressed as
      probability, there was a 66% chance that those with ASCVD >= 20 (vs. < 20) would
      have a residual specific-death during the follow-up period. CONCLUSION: The 10
      year predicted risk of a first ASCVD event via the PCR equations was directly
      associated with residual-specific mortality among those free of cardiovascular
      disease (CVD) at baseline, providing evidence of predictive validity of the PCR
      equations among this national sample of U.S. adults.

PMID- 27701987
TI  - Efficacy and safety of bladder hydrodistension for decreased bladder capacity
      induced by intravesical BCG therapy.
AB  - OBJECTIVE: Intravesical BCG therapy is widely used for the treatment of high
      risk, non-muscle-invasive bladder cancer. Among various reported side-effects,
      decreased bladder capacity is a serious side-effect that significantly worsens
      patients' quality of life. This article reports the efficacy and safety of
      bladder hydrodistension (BHD) in six patients with seriously decreased bladder
      capacity caused by BCG treatment. METHODS: Six patients with low bladder capacity
      (<100 ml in voiding diaries) and complaint of grade 3 irritative symptoms were
      diagnosed with decreased bladder capacity and treated with BHD. Alleviation of
      symptoms was defined as medication being discontinued or reduced after BHD.
      RESULTS: Five patients were male and one was female, and the mean age was 67.7
      years. The mean interval between the last transurethral resection and BCG therapy
      was 26.0 days. Before BHD, all patients had been treated with antibiotics,
      anticholinergics and non-steroidal anti-inflammatory drugs (NSAIDs). The median
      bladder capacity before treatment was 40 ml (range 30-100 ml), and the median
      capacity increased to 200 ml (175-250 ml) within 2 weeks following BHD therapy.
      Four patients stopped NSAID use and three patients stopped anticholinergic use.
      One patient needed total cystectomy for recurrent symptoms. With a median follow
      up period of 32 months, the bladder capacity remained stable without symptomatic
      deterioration in the remaining five patients. There was neither tumor spread nor
      disseminated tuberculosis infection. CONCLUSIONS: BHD appears to be an effective
      treatment option in patients with severely decreased bladder capacity. Its
      efficacy and safety were acceptable.

PMID- 27701988
TI  - Effect of particle size on oral bioavailability of darunavir-loaded solid lipid
      nanoparticles.
AB  - The present investigation aimed to study the effect of particle size of solid
      lipid nanoparticles (SLNs) on oral bioavailability of darunavir. High pressure
      homogenisation technique was used to prepare SLNs. Three different sized SLNs
      loaded with darunavir were developed with mean particle sizes of around 100 nm,
      200 nm and 500 nm, respectively. The in vivo pharmacokinetics in rats showed a
      significant increase in oral bioavailability of darunavir from all the three
      formulations in comparison to plain drug suspension and reference tablet. The
      results revealed insignificant difference between SLNs of 100 and 200 nm and
      these had significantly higher bioavailability in comparison to SLNs of 500 nm.
      However, more number of homogenisation cycles is required for obtaining 100 nm
      and thus we selected 200 nm as an optimum size for oral bioavailability
      enhancement of darunavir. The optimised SLN formulation was stable for a period
      of 6 months at 25 +/- 2  degrees C/60 +/- 5% relative humidity (RH).

PMID- 27701989
TI  - Promoting excellence in care.
AB  - Welcome to Nurse Researcher. This year's annual RCN International Nursing
      Research Conference was held recently in Cambridge, UK. The event, which
      attracted over 500 delegates from a range of diverse and academic settings across
      the world, brought together nurses and other healthcare professionals to promote
      and develop nursing knowledge. Over 200 papers and poster presentations covered a
      wide range of topics in nursing and healthcare research, including: issues in
      research methodology; education; theoretical perspectives; transcultural nursing;
      evidence-based practice; employment issues; and research governance. In addition
      to concurrent sessions and posters, many symposia, workshops and other fringe and
      networking events offered opportunities for sharing good practice and research
      collaboration. Next year's conference will be held in Belfast, Northern Ireland,
      UK from Tuesday 8 to Friday 11 March 2005. For more information visit:
      www.man.ac.uk/rcn/research2005.

PMID- 27701990
TI  - Gender and qualitative methods Helmi Jarviluoma Gender and qualitative methods ,
      Pirkko Moisala and Anni Vilkko Sage 152 L17.99 0761965858 0761965858 [Formula:
      see text].
AB  - This book is part of a series of texts exploring specific aspects of qualitative
      research. The series of books is particularly geared towards novice and
      inexperienced researchers. The text has an interdisciplinary and international
      focus. Issues relating to gender and qualitative methods are introduced by the
      authors through their own work and experiences of conducting qualitative studies.

PMID- 27701992
TI  - Doing and writing qualitative research Adrian Holliday Doing and writing
      qualitative research Sage L19.99 224 0761963928 0761963928 [Formula: see text].
AB  - This book is a very useful addition to the literature on qualitative methods,
      and, although it makes few direct references to nursing, midwifery or other
      health professions, I would have no difficulty in recommending it to postgraduate
      students interested in this approach or, indeed, to PhD candidates who were not
      familiar with the qualitative approach. I am sure they would find the author's
      clarity of style and skillfully chosen illustrations helpful as they sought to
      get to grips with the practicalities of qualitative methods.

PMID- 27701991
TI  - Nursing research in context: appreciation, application and professional
      development Nursing Research in Context: Appreciation, Application and
      Professional Development Dawn Freshwater Veronica Bishop Palgrave Macmillan
      L17.99 220 0333993543 0333993543 [Formula: see text].
AB  - Let's begin with what this book is not. This is, strictly speaking, not a 'how to
      do research' type book. It will not introduce the new researcher to the various
      research paradigms, nor will it explore the research process. This book will not
      take the reader through the different 'ologies' and 'ographies' to be found in
      research in any depth; neither will it examine, in detail, an assortment of
      different research methods that might be employed by a would be researcher.

PMID- 27701993
TI  - Mentally disordered offenders in Sweden: differentiating recidivists from non
      recidivists in a 10-year follow-up study.
AB  - BACKGROUND: Forensic psychiatric patients present a challenge as they manifest
      severe mental disorders together with criminal behaviour. There are well-known
      risk factors for criminal behaviour in the general population, yet knowledge of
      what predicts reconviction in the Swedish forensic population in the long-term
      perspective is still insufficient. AIMS: The study aims to (1) describe
      background and clinical characteristics of forensic psychiatric patients in a 10
      year follow-up, (2) analyse risk factors associated with recidivism, and (3) test
      the predictive validity of risk factors for general and violent criminality.
      METHODS: Detailed information on all offenders from the Malmo University Hospital
      catchment area sentenced to forensic psychiatric in-patient treatment from 1999
      2005 (n = 125) was collected. Court decisions were collected up until the end of
      2008 (median follow-up time = 6.2 years, range = 0.6-9.7 years). RESULTS: Relapse
      in general crime (n = 30) was predicted by low educational attainment, mental
      disorder in a first degree relative, and low age at first sentenced crime.
      Relapse in violent crime (n = 16) was predicted by low educational attainment and
      low GAF scores. Patients with a restriction order were less likely to relapse in
      both crime categories. CONCLUSIONS: Signs of childhood adversities together with
      early debut in criminality appeared as important risk factors for general and
      violent recidivism. Forensic psychiatric treatment combined with a restriction
      order was demonstrated as a protective factor against recidivism, suggesting that
      the risk of recidivism is strongly related to the level of supervision. Although
      the low number of recidivism cases is highly desirable, it unfortunately reduces
      the power of the analyses in this paper.

PMID- 27702010
TI  - Qualitative Research PracticeEditors: Clive Seale , Giampietro Gobo , Jaber F
      Gubrium , David Silverman Qualitative Research Practice Sage Edition: First 552
      L29.99 1412934206 1412934206 [Formula: see text].
AB  - This book is jam-packed with a wide range of material related to qualitative
      research. The editors and contributors are drawn from a wide international
      background, and thus, say the editors, the book represents 'the global nature of
      the qualitative research enterprise'. The aim in producing it was not simply to
      produce another handbook of qualitative research but rather to write a book about
      research practice. To this end, the book draws upon actual research studies to
      embed the text in the real world of qualitative research. It is particularly
      aimed at the student reader.

PMID- 27702011
TI  - Organizing and managing your research: a practical guide for postgraduates Renata
      Phelps Organizing and managing your research: a practical guide for postgraduates
      , Kath Fisher and Allan Ellis Sage Edition: First 304 L19.99 1412920643
      1412920643 [Formula: see text].
AB  - This is a first edition of a new book designed to help postgraduate students
      manage and organise their research projects. As a current PhD student and
      supervisor of undergraduate and postgraduate students, I was intrigued to see
      what this book could offer.

PMID- 27702012
TI  - Researching the Vulnerable Pranee Liamputtong Researching the Vulnerable Sage
      Edition: First 256 L21.99 1412912547 1412912547 [Formula: see text].
AB  - This book is refreshing, both as an addition to the general research literature
      and as a text that considers cultural and social issues in studies relating to
      improving the situation of vulnerable people - a group that forms such an
      important focus of a great deal of health and social research.

PMID- 27701994
TI  - Clinical impact of metformin in diabetic diffuse large B-cell lymphoma patients:
      a case-control study.
AB  - Molecular studies have shown metformin to have a promising effect in lymphoma;
      however, there is lack of studies translating this effect into clinical settings.
      This was a case-control study to assess the clinical effect of metformin in
      diabetic diffuse large B-cell lymphoma (DLBCL) patients. Case subjects were
      diabetic on metformin with a new diagnosis of DLBCL. A total of 24 case subjects
      were identified, and for each case a control was matched. Outcomes of this study
      were to assess overall response rate, complete remission rate, progression free
      survival, and overall survival between the two groups. There was a significant
      increase in overall response rate, complete remission rate, and improved
      progression free survival in the metformin group compared to the control group,
      however, no significant overall survival difference was observed. Metformin use
      might be associated with an improved response rates and progression-free survival
      in diabetic DLBCL patients.

PMID- 27702014
TI  - Personal experiences of designing questionnaires.
AB  - So much for the theory, hut what about the practice? Donna Mead provides an
      account of creating, implementing and evaluating questionnaires, drawn from her
      own research.

PMID- 27702015
TI  - Questionnaires: Use, value and limitations.
AB  - To some people, they are a necessary nuisance; to others, they are simply a
      nuisance. Opinion pollsters swear by them, while 'qualitative researchers' swear
      at them. Except for a lucky few, we all have been subjected to them. Millions of
      pounds are spent on them annually. For those who use them, they provide the
      quickest way to collect large amounts of data from large samples of population,
      often scattered over wide geographical areas, comparatively cheaply. They are
      called questionnaires, and are the most common form of data collection tool.

PMID- 27702016
TI  - Editorial.
AB  - Each time I design a questionnaire, I seem to make a different mistake'. So
      writes Donna Mead in this issue of Nurse Researcher, and she is reflecting the
      feelings of many nurses who have attempted this complex task. We have tried to
      unravel some of the mysteries involved in questionnaire design, pointing out the
      pitfalls and emphasising the positives.

PMID- 27702017
TI  - Studying policy and practice: Use of vignettes.
AB  - The authors explore the use of vignettes in their research work, and claim that
      the method can supply systematic information on professional practice and the
      policies which underlie it, information that is not easily obtained by other
      means.

PMID- 27702018
TI  - Approaches to analysis and interpretation.
AB  - The authors look at some common methods of identifying the important information
      from questionnaire data, pointing out some of the pitfalls researchers can find
      in their way.

PMID- 27702019
TI  - Promoting nursing research: The RCN's role.
AB  - Nursing is not and cannot be immune from the economic and political influences
      which are forcing fundamental reassessments of the effectiveness of different
      models of health care delivery.

PMID- 27702020
TI  - Simulation in training questionnaire design.
AB  - Teaching students about the practicalities of questionnaire design and
      application can raise serious ethical problems if patients are involved in their
      research. The authors describe how the skills can be effectively taught without
      recourse to involving patients at all.

PMID- 27702021
TI  - Sampling and distribution issues.
AB  - Questionnaires are typically concerned with general pictures of the experiences
      of groups of individuals, rather than with highly detailed, specific examinations
      of small numbers of individuals. The questions they seek to answer are also
      broad, with particularly highly structured questionnaires consisting principally
      of closed-ended questions.

PMID- 27702022
TI  - Questionnaire design and construction.
AB  - A poorly considered and designed questionnaire can yield extremely unreliable
      results. Elaine McColl examines the steps a researcher has to take to ensure that
      only the most valid instrument is created.

PMID- 27702024
TI  - Validation: choosing a test to fit the design.
AB  - Any questionnaire must help the researcher find answers to the questions he or
      she is asking. But this is not as simple as it sounds. Maureen Eby describes ways
      of defining validity and reliability.

PMID- 27702025
TI  - ?
AB  - This qualitative study analysed interviews with ten nurses working in a Swedish
      special care unit for older people with Alzheimer's disease. The themes
      identified included 'encouraging a sense of belonging', 'providing opportunities
      for occupation', 'adjusting oneself to the resident', and 'striving to promote a
      sense of self in the resident'. The researchers conclude that there is a need to
      articulate the meanings of such commonly used terms as 'good care' or 'homelike
      environment', so that they may become more than mere aspirations. 43 references.

PMID- 27702026
TI  - Implementing research in the clinical setting: the road map for implementing
      research Chris bassett Implementing research in the clinical setting: the road
      map for implementing research whurr publishers no of pages: 116 L17.50 0861562845
      0861562845.
AB  - There are many excellent books that focus on research methodologies, but this one
      has adopted a different approach focusing on how research can be implemented in
      practice settings. In doing so, the authors removes the mystic and jargon that is
      often attributed to research. making research seem both logically and accessible 
      a feat in itself!

PMID- 27702027
TI  - Surviving your dissertation Kjell Rudestam Surviving your dissertation , Rae
      Newton Sage 298 L19.99 0761919627 0761919627.
AB  - Reviews and round-up A regular look at recent publications and forthcomingn
      events, courses and information relevant to health care and nursing research.

PMID- 27702156
TI  - Cash commitment to end bed-blocking.
AB  - The government last month announced a L300 million cash injection to help
      overcome the problem of bed-blocking, which results in thousands of older people
      being forced to wait in acute hospitals after their treatment is over.

PMID- 27702066
TI  - Rouleau version of the Clock Drawing Test: age- and education-adjusted normative
      data from a wide Italian sample.
AB  - OBJECTIVE: The Clock Drawing Test (CDT) is widely used as a screening tool for
      discriminating cognitively normal individuals from patients with mild dementia.
      The aim of present study was to provide normative values for a 10-point
      quantitative scoring system proposed by Rouleau and colleagues (1992), including
      CDT total score and subscales score assessing representation of clock face (RC),
      layout of numbers (LN), and position of hands (PH), in a large sample of Italian
      healthy individuals. METHOD: Eight hundred and seventy-two Italian healthy
      participants (483 women; age range 20-94 years) with educational level from
      primary school to university underwent CDT and Mini Mental State Examination
      (MMSE). RESULTS: Multiple linear regression analysis revealed that age and
      education significantly influenced CDT total score and its subscale scores.
      Moreover, a significant effect of gender was found only in RC subscale. From the
      derived linear equation, a correction grid for raw scores was built. Inferential
      cut-off values were estimated using a non-parametric technique and equivalent
      scores (ES) were computed. Correlation analysis showed a weakly significant
      correlation between adjusted CDT total score and adjusted MMSE scores.
      CONCLUSIONS: The present study provided normative data for the Rouleau and
      colleagues version of CDT in an Italian sample, useful for clinical and research
      purposes.

PMID- 27702158
TI  - Fighting off 'flu.
AB  - All manner of coughs, colds and sneezes are passed off as 'the 'flu' but anyone
      who has experienced the dreadful spirit-sapping incapacity of the true virus will
      know that those who proclaim to have it while remaining upright misunderstands
      its true nature. The aching limbs, the lethargy, the headaches - it's like being
      crushed by a barn door, while having a nose running like a tap and a cough to
      wake the dead. If you're young and fitish, you emerge from the experience a few
      days later weakened and washed out, but essentially alive. If you're an older
      person, however, or one whose immunity is already compromised, the consequences
      can be fatal. And the threat is particularly acute in epidemic years: 29,000 died
      from 'flu in 1989/90, although even in an 'average' year, 12,000 deaths are
      linked to 'flu activity.

PMID- 27702159
TI  - ?
AB  - There is concern among researchers in the United States that some communities
      predominantly settled by members of minority ethnic groups have lower levels of
      nursing home provision than the average for the society as a whole. Similarly,
      there is some evidence that elders from such communities may be 'steered' towards
      segregated facilities. Data from the 1990 US Census of Population and the 1994
      Illinois Long-Term Care Facility Survey were analysed to see what patterns
      emerged for the Chicago area. The results showed that both African American and
      Latino nursing home residents tend to be found in their own neighbourhoods,
      although overall Latinos demonstrated the greater mobility. 19 references.

PMID- 27702160
TI  - Principles of pain assessment in older people - part 1.

PMID- 27702161
TI  - Editorial.
AB  - The randomised controlled trial (RCT) enjoys a mixed reputation in nursing. What
      it represents and its appropriateness in nursing research are at once lauded and
      reviled by large numbers of nurses and nurse researchers.

PMID- 27702162
TI  - Evaluation of education for people with osteoarthritis of the knee: recruitment
      and retention issues in study design.
AB  - Osteoarthritis (OA) is a common and often disabling condition affecting older
      adults. Treatment using anti-inflammatory drugs (NSAIDs) often contributes to
      morbidity ( 1 ). It is a common reason for people seeking help from primary care
      ( 2 ). However, unfortunately management approaches often reflect the ageist view
      that OA is an inevitable consequence of ageing.

PMID- 27702163
TI  - Patient recruitment and retention strategies in randomised controlled trials.
AB  - Evidence-based practice has become a by-word for health care in the 1990s.
      However, the idea of founding practice on evidence rather than anecdote or
      tradition has a much longer history. In the 1970s, Cochrane ( 1 ) was already
      arguing the need for the widespread use of randomised controlled trials (RCTs) to
      inform practice, not only with a view to identifying the most effective clinical
      treatments, but also the equitable and economical means of utilising those
      treatments.

PMID- 27702164
TI  - Developing research methods in qualitative research: using a radio microphone in
      a pilot study.
AB  - The diploma of higher education in nursing aims to produce a first level
      registered nurse with the necessary knowledge and skills to work safely as a
      competent practitioner. Implicit in this aim is the requirement for the nurse to
      be an effective commmunicator of diverse and sometimes complex information
      requiring application of knowledge and skill. The diploma incorporates health as
      a major theme in the curriculum.

PMID- 27702165
TI  - Developing a protocol for a randomised controlled trial: factors to consider.
AB  - Randomised controlled trial (RCT) research designs are generally considered to be
      the most rigorous way of determining whether a cause and effect relationship
      exists between an intervention/treatment and outcome, and for assessing the
      effectiveness, including cost- effectiveness, of an intervention or treatment ( 1
      ). Studies employing such designs play an important role in nursing, as in all
      aspects of healthcare, because of the need to establish the evidence base for
      practice and to be able to predict the likely consequences of certain events and
      interventions under given conditions. This is important not only with respect to
      patient care but also to inform policy, planning and allocation of resources( 2
      ).

PMID- 27702166
TI  - Focus group interviews as a methodology.
AB  - Focus groups are a form of group interview used widely in social science
      research. It is a methodology that has also been applied in a number of areas of
      healthcare study, particularly in health promotion and consumer satisfaction.
      First described by Bogardus in 1926 ( 1 ). focus groups fuse the principles of
      qualitative research and group process theory. Morgan ( 2 ) suggested that: 'The
      explicit use of group interaction is to produce data and insights that would be
      less accessible without the interaction found in a group.'

PMID- 27702168
TI  - Interviewing women from an ethnic minority group: finding the sample, negotiating
      access and conducting semi- structured interviews.
AB  - While interviewing GPs in 1995 and 1996 about their referral decisions for women
      with menorrhagia, I became aware that some areas in the UK may have relatively
      poor gynaecology services ( 1 ). Moreover, in one town with a large ethnic
      minority (15.4 per cent of the population) GPs informed me that they believed
      that women of South Asian descent with menorrhagia had particular difficulties in
      obtaining treatment, mainly because of the shortage of female doctors ( 2 ).

PMID- 27702169
TI  - The randomised controlled trial: a critique.
AB  - Traditionally, health care has been based on historical legacy, personal
      treatment preferences and ritual. Indeed in the present day, some health
      professionals persist not only in practising clinical interventions that are
      known to be ineffective, but also fail to introduce others that tire known to
      have good outcomes, resulting in inescapably huge variations in practice and
      treatments ( 1 ).

PMID- 27702170
TI  - ?
AB  - This paper represented a collaborative project between researchers in Mexico and
      the USA, using Roy's Adaptation Model as its theoretical basis. A sample of 50
      older women drawn from two socially and economically disadvantaged areas in
      Mexico formed the sample. A questionnaire was used to explore both the women's
      roles in society and their participation in exercise. The findings indicated that
      40 per cent of the sample were contemplating some type of exercise. The authors
      found this total surprisingly high, as exercise has not been a social norm for
      older women in this section of society. The opportunities for health promotion
      are discussed. 21.

PMID- 27702171
TI  - Challenging behaviour in dementia: a person-centred approach Graham Stokes
      Challenging behaviour in dementia: a person-centred approach Winslow 256pp L22.25
      0-86388-250-1 0863882501 [Formula: see text].
AB  - This book aims to show readers that behaviours in people with dementia tend to be
      wrongly or poorly described and that this can lead to a misunderstanding of how
      best to understand or respond to both the behaviours and the person. The author
      makes a strong case for greater observation and assessment of a range of
      behaviours and their influencing factors. He also argues that interventions must
      be underpinned by a person-centred approach and with empathy for the subjective
      experience of people with dementia. The book should appeal to nurses, care
      assistants and other health care professionals as well as people working in the
      voluntary sector.

PMID- 27702173
TI  - Letters.
AB  - Letters to the Editor are welcome. Send to The Editor, Nursing Older People, 17
      19 Peterborough Road, Harrow, Middlesex HA1 2AX. We reserve the right to edit
      letters.

PMID- 27702172
TI  - Funding nursing care.
AB  - Pauline Ford explains some of the thinking behind the RCN's response to the
      government's proposals for funding registered nursing.

PMID- 27702175
TI  - New publications Barry Turner New publications , Editor Care Choices Ltd Tel:
      0800 389 2077 160pp L12.99 1-898597-05-7 1898597057 Elizabeth Scott St George's
      Nurses League, c/o Chief Nurse's Office, Room 32, 1st Floor Grosvenor Wing, St
      George's Hospital, London SW17 0QT 165pp L12.50+L1.20 p&p Don Brand and Peter
      Fletcher National Institute for Social Work/National Housing Federation L15 plus
      L2.50 p&p (cheque payable to National Housing Federation) 0-86297-452-6
      0862974526 Moya J Morison (editor) Mosby 267pp L24.95 0-7234-3158-2 0723431582.
AB  - Practical handbook offering advice on finding and funding care for adults with
      disabilities. Also lists more than 500 useful advisory organisations, indexed by
      subject, from abuse through travel and holidays to women's health.

PMID- 27702177
TI  - ?

PMID- 27702176
TI  - Website watch.
AB  - ?Dementia Voice is the Dementia Servic Development Centre for the Southwest of
      England and aims to promote service development and best practice in dementia
      care. They provide information, training and consultancy services to professional
      carers in the field of dementia care. Dementia Voice also undertakes research
      work and develops other specific projects. www.dementia-voice.org.uk/.

PMID- 27702178
TI  - Still the best medicine laughter.
AB  - which also says 'and what are you going to do about it?' but her reply always
      makes me laugh. 'So I see' - I join her in stating the obvious, and we look at
      one another and smile.

PMID- 27702179
TI  - Exchange network wales.
AB  - Promoting the value of nursing with older people is a priority of both the RCN
      Advisory Panel and the Nursing and Care Homes Forum in Wales. There is good care
      practice which needs to be highlighted, praised and shared for the benefit of the
      public and the profession. However, there is also poor, underdeveloped and
      entrenched practice about which we sadly hear in the media. This has concerned me
      for some time ( Morgan 1992 ). There needs to be a mechanism whereby nurses can
      share practice which is person-centred, high quality and offers the best to the
      public. I see the RCN, and particularly the forums, as the professional
      organisation to take this forward.

PMID- 27702180
TI  - Tai Chi for older people.
AB  - Classes are held in a variety of venues, in order to be accessible to as many
      older people as possible. Each has its own dynamic and atmosphere.

PMID- 27702182
TI  - The dilemmas of putting a price on care.
AB  - While welcoming the government's decision to fund nursing in nursing homes, older
      people, professional organisations and MPs from all parties are unitedly calling
      for England and Wales to follow Scotland's lead and implement the Royal
      Commission's recommendation that personal care be provided free on the basis of
      assessed individual need.

PMID- 27702181
TI  - Events.
AB  - : Benefits and Residential Care Disability Alliance Training Unit Fee: L75
      members, L90 non-members Venue: London Voluntary Sector, Resource Centre, 356
      Holloway Road, London. CONTACT: Valerie Grant, Disability Alliance, Universal
      House, 88 - 94 Wentworth Street, London E1 7SA. Tel: 020 7247 8776, fax: 020 7247
      8765, Website: www.disabilityalliance.org.

PMID- 27702184
TI  - NICE go-ahead for alzheimer's drugs.
AB  - The end of 'postcode prescribing' heralded by the long awaited National Institute
      for Clinical Excellence decision on drugs for Alzheimer's disease has been
      welcomed by the Alzheimer's Society. This will mean that the three drugs
      currently licensed in the UK and used to alleviate the symptoms of Alzheimer's
      disease, Aricept, Exelon and Reminyl, should be made available through the NHS
      across England and Wales. Research carried out at the Maudsley Hospital, London
      last October showed that half of health authorities failed to provide funds to
      enable people with Alzheimer's disease to benefit from treatment.

PMID- 27702186
TI  - How to Design and Report Experiments Andy Field How to Design and Report
      Experiments and Graham Hole Sage No of pages: 400 L18.99 0761973834 0761973834
      [Formula: see text].
AB  - Over the years, I have been in a fortunate position of being asked to review a
      very large number of books. These have included contributions on a number of
      areas. As well as the usual research- focused references, I have been asked to
      review autobiographical and historical works. Generally speaking, books of the
      latter category are the easiest read and contrast with the books on the topic of
      designing and reporting experiments.

PMID- 27702187
TI  - How to study: a short introduction Joan Turner How to study: a short introduction
      Sage 162 L9.99 0761968083 0761968083 [Formula: see text].
AB  - This book, aimed at undergraduates and students preparing for university courses,
      includes in its stated aims the building of confidence and competence in academic
      life by introducing students to both academic culture and the academic tasks that
      will be required of them.

PMID- 27702192
TI  - Foundation Studies for Nursing: Using enquiry based learning Sue Grandis
      Foundation studies for nursing: Using enquiry based learning , Garth Long ,
      Palgrave Alan Glasper and Pam Jackson 482 L19.99 0333777387 0333777387 [Formula:
      see text].
AB  - Although problem-based learning (PBL) or enquiry-based learning (EBL) has been
      used in medical education in the UK, its use as a teaching approach in nurse
      education is embryonic. Few nursing curricula employ a purely EBL/PBL approach -
      although many courses are beginning to include it as a teaching method.

PMID- 27702196
TI  - Authoring a PhD Patrick Dunleavy Authoring a PhD Palgrave Macmillan No of pages:
      300 L16.99 1403905843 1403905843 [Formula: see text].
AB  - This is a clever book. The author has recognised that potential PhD students are
      offered thorough advice regarding their chosen topic as well as areas such as
      data analysis, but when it comes to the crucial area of authoring skills advice
      can be scant or non-existent. This is clearly an oversight on the part of many
      educational establishments; the skills required in authoring a 'big book' style
      of PhD of some 80,000 to 100,000 words from conceptualisation through to
      completion are not innate.

PMID- 27702194
TI  - RCN research developments.
AB  - The most frequently asked questions that the RCN receives from its members in
      relation to research matters pertain to the ethical issues associated with
      research activities. For this reason, the RCN Research Society has been under-
      taking work under the theme of Research Governance which we are delighted to
      launch in this edition of Nurse Researcher. Published here in full is the updated
      RCN Research Society guidance on ethics related to research. This document will
      be ultimately made available on the RCN Research Society website
      http://www.man.ac.uk/rcn/rs/index.htm .

PMID- 27702197
TI  - Qualitative research in nursing Immy Holloway Qualitative research in nursing and
      Stephanie Wheeler Blackwell 304 L18.99 0632052848 0632052848 [Formula: see text].
AB  - This is a lively and interesting book, which is broken up into four main
      sections. The first is an introduction to qualitative research. This is a
      thorough introduction to qualitative research, and covers the arguments between
      the various schools of thought, as well as helpful topics such as the initial
      steps necessary, writing a research proposal, ethical issues and supervision.

PMID- 27702199
TI  - Grounded Theory: A practical guide for management, business and market
      researchers Christina Goulding Grounded Theory: A practical guide for management,
      business and market researchers Sage Publications No of pages: 186 L18.99
      0761966838 0761966838 [Formula: see text].
AB  - Much has been written about the grounded theory approach to qualitative research,
      however the number of books devoted solely to this methodology remains relatively
      few. Therefore, any new book dedicated to the subject is always likely to attract
      attention - especially given the increasing popularity of grounded theory in
      healthcare research.

PMID- 27702201
TI  - Conferences.

PMID- 27702203
TI  - The royal college of nursing research society: nurses and research ethics.
AB  - The RCN has published its influential guidance on research ethics for nurses
      since 1977, and these have been regularly revised, most recently in 1998. The
      pace of change is rapid however, and the RCN was mindful of a number of reasons
      to revisit the guidance.

PMID- 27702202
TI  - Rigorous governance, yes - but let's get the controls right.
AB  - We are pleased to introduce this issue of Nurse Researcher about research
      governance and ethics when interest in these matters is so high. In the UK this
      can be partly explained by interest generated by scandals in the medical research
      community, most notably the retention of children's organs without consent at
      Alder Hey Hospital, and the consequent government priority attached to more
      rigorous governance procedures.

PMID- 27702204
TI  - NVQs reliable indicators of competence?
AB  - Most care professionals acknowledge that training for healthcare workers should
      improve standards of care for clients. The current emphasis is on NVQs. Manthorpe
      ( 2002 ) identifies training as an important component of preventing abuse within
      the care setting, stressing the value of using materials linked to S/NVQ in Care
      for the unit Z1, titled 'Contribute to the protection of individuals from abuse'.

PMID- 27702205
TI  - Admiral nurses competency project.
AB  - The Admiral nurses competency project was funded by the Dementia Relief Trust and
      carried out by the RCN Gerontological Nursing Programme (GNP) over 20 months.
      Working with the Admiral nurses, part-time project facilitators used an action
      research approach to develop a competency framework with higher level
      competencies. Last year we described the methods being used ( Traynor and Dewing
      2001 ). This article describes the final stages and implications of the work for
      specialist practitioners and nurses working with people with dementia and their
      carers.

PMID- 27702206
TI  - Care environments influence student perceptions.
AB  - Positive experience of work with older people is one of the key influences
      determining whether the specialty is seen as interesting and exciting and is
      viewed as an attractive future career option, according to research conducted for
      the English National Board.

PMID- 27702208
TI  - Wasting time?
AB  - In February the Department of Health launched guidance designed to help local
      health and social care agencies introduce a single assessment for older people.
      Although the concept of a single assessment is set out in more detail in the
      National Service Framework for Older People, the overall aim, according to the
      Department of Health (2002) is to: 'Ensure that older people receive appropriate,
      effective and timely responses to their health and social care needs, and that
      professional resources are used effectively. In pursuit of these aims, the single
      assessment process should ensure that the scale and depth of assessment is kept
      in proportion to older people's needs; agencies do not duplicate each other's
      assessments; and professionals contribute to assessments in the most effective
      way.'

PMID- 27702209
TI  - Side rails: the need for appropriate assessment.
AB  - Side rails, or 'cot-sides' as they have been widely known, have always been used
      so freely both in hospitals and nursing homes since I started my career in 1981
      that, prior to reading this article, I never considered them as anything more
      than safety equipment that prevents a patient falling out of bed. The thought of
      careful risk-assessment and gaining consent prior to their use had never crossed
      my mind.

PMID- 27702210
TI  - Things can only get better.
AB  - recently by the Audit Commission, updates the findings of the original Forget Me
      Not first published in 2000, which highlighted significant gaps in mental health
      services for older people. The latest publication is based on an extensive
      investigation of local services and includes the responses of 5,000 carers and
      8,000 GPs from all over England.

PMID- 27702211
TI  - ?
AB  - Most professionals working with older people favour a 'needs led' assessment
      process in which the individual's needs form the agenda for action. It does not
      prove easy, however, to ignore professional and organisational agendas when
      assessing patients' needs. In this fascinating experimental study, the discharge
      arrangements made by three multidisciplinary teams were reviewed. The team led by
      an occupational therapist arranged the most occupational therapy services and
      equipment, and their patients received the most home care. The team led by a
      social worker referred the most patients for care assessment and their patients
      received the greatest range but not the greatest amount of services. The nurse
      led team was least likely to refer patients for care assessment and their
      patients received the least services after discharge. 27 references.

PMID- 27702212
TI  - A moment in history.
AB  - A memorable moment in history was enriched by thousands of people of all ages
      wanting to show gratitude for the life of one of our older citizens. The death of
      Her Majesty Queen Elizabeth the Queen Mother evoked innumerable personal
      tributes. It also prompted the expression of a wide range of views about the
      value and relevance of older people in the world today.

PMID- 27702213
TI  - International handbook of curriculum research William F Pinar International
      Handbook of Curriculum Research Lawrence Erlbaum Associates 712 L54.95 0805845356
      0805845356 [Formula: see text].
AB  - William Pinar has edited a vast but coherent compendium which will be invaluable
      to anyone wishing to research different national traditions of curriculum
      research, and to gain some understanding of curriculum debates in the 28
      countries that this book covers.

PMID- 27702218
TI  - Constructing Grounded Theory: A practical guide through qualitative analysis
      Kathy Charmaz Constructing Grounded Theory: A practical guide through qualitative
      analysis Sage 224 L19.99 0761973532 0761973532 [Formula: see text].
AB  - The grounded theory approach to doing qualitative research in nursing has become
      very popular in recent years. I confess to never really having understood Glaser
      and Strauss' original book: The Discovery of Grounded Theory. Since they wrote
      it, they have fallen out over what grounded theory might be and both produced
      their own versions of it. I welcomed, then, Kathy Charmaz's excellent and
      practical guide.

PMID- 27702214
TI  - Handbook of action research Peter Reason and Hilary Bradbury Handbook of action
      research Sage 400 L29.99 1412920302 1412920302 [Formula: see text].
AB  - This book represents the concise paperback edition of a seminal work on action
      research. The hardback version has for the past few years been an excellent
      source of knowledge on the many different approaches to action research in a wide
      range of contexts and settings. The original book is by no means a beginners'
      compendium; action research is a broad church, but without an understanding of
      how it compares with other research strategies, the niceties of some of the
      variants can be elusive. For example, some would argue that action research is
      necessarily underpinned by critical theory and that it is always conducted in the
      participatory, transformative mode. Looking down the list of chapters, one would
      be forgiven for thinking this to be so, but a much closer scrutiny demonstrates
      that action research has a long history, along a continuum of 'highly
      theoretical' to 'very pragmatic' and in many fields including education, health
      care, social situations and organisations.

PMID- 27702219
TI  - Collins internet-linked dictionary of medicine RM Youngson Collins Internet
      linked Dictionary of Medicine Collins 704 L9.99 0007207093 0007207093 [Formula:
      see text].
AB  - This quite comprehensive internet-linked dictionary covers all of the major
      systems and some of the pathophysiological conditions that are relevant to those
      systems. Many physiological/clinical terms have been used, which both medical and
      non-medical individuals may use as a basis for future information. The text
      includes terms and phrases that are applicable to the healthcare community and
      those associated with it. The diagrams that have been included are well presented
      and the websites fairly comprehensive. The cost of the text seems in line with
      many similar texts of this ilk.

PMID- 27702220
TI  - A Practical Guide to Research Methods Catherine Dawson A Practical Guide to
      Research Methods howtobooks 170 L9.99 1845280792 1845280792 [Formula: see text].
AB  - The world of research can certainly be confusing. The new researcher is exposed
      to complex methodological issues, inexact or conflicting terminology, and
      frequently to research authors who pursue their own foibles at the expense of
      comprehension. book. There are a number of issues which are touched upon, but not
      really explored, for example, triangulation. Now this is a large topic in itself,
      and it would be unreasonable to suggest that a slim volume such as this can cover
      all topics relevant to social science/nursing research, nor that any author
      should try to do this. What this does highlight, though, is that, although this
      book may be a useful point of departure, the students will still have to read
      widely and be in a position to compare and contrast sources to justify their
      choices of methodology and methods. This is particularly true for students aiming
      for higher degrees. Similarly, topics such as choice of paradigms, which are
      largely mandatory for higher degrees, are not included here.

PMID- 27702222
TI  - Essentials of nursing research: methods, appraisal, and utilization Denise F
      Polit Essentials of nursing research: methods, appraisal, and utilization ,
      Cheryl Tatano Beck Lipincott Williams and Wilkins 554 L24.95 0781749727
      0781749727 [Formula: see text].
AB  - Perhaps not obvious from the title, this book is designed to guide the reader
      through the process of finding, reading, and critically evaluating published
      nursing research, and to consider the practical use to which research findings
      may be put. The reader is led systematically through the stages of finding
      published studies (with reference to widely available databases), reviewing them
      in relation to their ethical implications and theoretical bases, scrutinising
      their design, sampling, data collection and analysis methods, and evaluating the
      quality of the data generated. Guidelines for producing a written critique of
      published studies are provided. The book ends with a focus on using research
      evidence, referring to key models for evidence-based nursing practice. While
      barriers to research utilisation are discussed, a greater emphasis on this topic
      might have been expected, given the inclusion of research utilisation within the
      book's title.

PMID- 27702223
TI  - Getting research published: an A-Z of publication strategy Elizabeth Wager
      Getting research published: an A-Z of publication strategy Radcliffe 152 L21.95
      1857756878 1857756878 [Formula: see text].
AB  - Any book that begins to unravel the mysteries of getting research published is to
      be welcomed with open arms by the nurse who is hoping to get his or her work into
      print. This book is an A-Z guide to publication strategy, written by an extremely
      experienced author of research publications. Elizabeth Wager has been an editor
      for Blackwell Scientific as well as an author for various drug companies, and is
      now a freelance writer.

PMID- 27702226
TI  - A mathematical model for the interplay of Nosema infection and forager losses in
      honey bee colonies.
AB  - We present a mathematical model (a) for the infection of a honey bee colony with
      Nosema ceranae. This is a system of five ordinary differential equations for the
      dependent variables healthy and infected worker bees in the hive, healthy and
      infected forager bees, and disease potential deposited in the hive. The model is
      then (b) extended to account for increased forager losses, e.g. caused by
      exposure to external stressors. The model is non-autonomous with periodic
      coefficient functions. Algebraic complexity prevents a rigorous mathematical
      analysis. Therefore, we resort to computer simulations in addition to some
      analytical results in the constant coefficient case. We investigate each of the
      two stressors (a) and (b) individually and jointly. Our results indicate that the
      combined effect of two stressors, both of which can be tolerated by the colony
      individually, might lead to colony failure, suggesting multi-factorial causes
      behind losses of honey bee colonies.

PMID- 27702227
TI  - End of ' a good innings' and the start of something better?
AB  - The long awaited and much delayed National Service Framework (NSF) for older
      people is to be welcomed by all who work in, teach about and research the care of
      older people. The NSF is broad, addressing the work of doctors, social workers
      and nurses, among others.

PMID- 27702228
TI  - Involving relatives and friends Involving relatives and friends Julia Burton
      Jones Relatives and Residents Association L8 57pp 1 900216 02 7 1900216027.
AB  - An excellent reference document for prospective residents and their families and
      also a useful source of information for managers and staff. The book is set out
      clearly and unambiguously, enhanced with many examples of good practice which are
      both positive and practical.

PMID- 27702229
TI  - Staying sane: managing the stress of caring Tanya Arroba Staying sane: managing
      the stress of caring and Lesley Ball Age Concern L14.99 102pp 0862422671
      0862422671 [Formula: see text].
AB  - A super little book which clearly sets out the reasons for stress, how it can
      occur, and how to manage it effectively. Caring has become more demanding and
      more stressful and this is recognised by both authors: Tanya Arroba and Leslie
      Bell, who have many years of experience in care of the adult. They reiterate the
      fact that it is an area that needs to be taken seriously as demands on the carer
      can become greater and work which is potentially rewarding can become over
      shadowed by stress.

PMID- 27702232
TI  - Art works.
AB  - As a fine art graduate I have run painting groups in a number of care settings
      and worked in one care home for over 10 years. A member of the group I ran there
      died recently at the age of 97. I had worked with Winifred from the very first
      session and at her funeral service the minister spoke of how she had joined an
      art group in her care home and about how thrilled she was to discover that she
      could paint pictures - landscapes, birds and still life. She had said to her
      friends and family how she wished she had been given the opportunity to paint
      earlier in her life because she found so much pleasure in it.

PMID- 27702231
TI  - ?
AB  - Lesley Rudd has been appointed as director of healthcare service development for
      Westminster Healthcare. She previously worked as joint regional director of
      nursing, human resources and patient involvement for the South West Regional
      Office of the NHS Executive.

PMID- 27702233
TI  - Time to demolish the myths surrounding sexuality.
AB  - The Victorians knew a thing or two about building bridges, railways and tunnels
      and could knock up grand and imposing buildings at the drop of a top hat. But
      while their engineering and construction skills helped drive on the modern age,
      when it came to formulating a progressive attitude towards sex they were
      clueless.

PMID- 27702234
TI  - Sex and the older woman.
AB  - Nurses, doctors and other health professionals need more training to help them
      understand the sexual lifestyles of older women, says a new study commissioned by
      the Pennell Initiative for Women's Health.

PMID- 27702235
TI  - ?
AB  - Thank you so much for 'The Nightingale legacy' article (May 2001) about Lea
      Hurst, the AgeCare residential home in Derbyshire, which admirably proves the
      point that not all care homes are terrible places. What impressed me more than
      anything was the involvement of residents in interviewing prospective members of
      staff. I'd like to think this practice is widespread but am willing to bet very
      few care homes give residents a voice and a choice in who gets to look after
      them. Maybe your readers can prove me wrong.

PMID- 27702237
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27702236
TI  - ?
AB  - This paper summarises some of the findings of a major research project, funded by
      the English National Board, on the nurse's role in rehabilitation. An extensive
      literature review using a wide range of databases was conducted in order to
      elucidate the nurse's role in patient education. This approach was supplemented
      by curriculum analysis based on course documentation drawn from a range of pre
      registration diploma and degree courses, together with a range of post
      registration courses. The conclusion drawn is that while the literature argues
      for the central importance of patient education in the rehabilitation process,
      curriculum analysis suggests that nurses are not adequately prepared for this
      aspect of their role. 98 references.

PMID- 27702238
TI  - Still Rockin.

PMID- 27702239
TI  - Website watch.
AB  - Useful websites on osteoporosis ? This is the obvious place to begin a search for
      information - the National Osteoporosis Society's site. It includes sections
      aimed at people with the disease as well as information for health professionals.
      Includes a useful publications section. www.nos.org.uk.

PMID- 27702240
TI  - Longitudinal comparison of depression, coping, and turnover among NHS and private
      sector staff caring for people with dementia.
AB  - Staff turnover is often high in both NHS and private sector facilities caring for
      people with dementia, so the authors of this study set out to test the hypothesis
      that stress plays an important role in this issue.

PMID- 27702241
TI  - ?
AB  - Isabela Hannah (left) was the first new resident at the newly refurbished and
      expanded West Midlands Co-op Castle Meadows Care Home in Dudley. She is pictured
      with fellow resident Gwen Smith. The Co-op is believed to be the first society of
      its kind to move into the care homes sector.

PMID- 27702242
TI  - New report details implications of Human Rights Act for older people.
AB  - Help the Aged has launched a report detailing the implications of the Human
      Rights Act for older people and for the public bodies responsible for providing
      services to them.

PMID- 27702243
TI  - A special case.
AB  - The traditional boundaries between professional groups are under scrutiny in
      response to practice development, local service needs and national policy
      objectives. This has implications for the roles, work patterns and education of
      all health and social care staff and may even offer a new career option for
      nurses working with older people - an older people's specialist nurse role
      (OPSN).

PMID- 27702244
TI  - A full agenda.
AB  - By the time you read this a new government will have been elected and RCN
      Congress will have come and gone. How do we, as nurses caring for and working
      with older people with mental health needs, engage in these events? The policy
      agenda concerning older people has never been fuller but does all this activity
      ignite within you a desire to act for the greater good of nursing and older
      people, or does it make you feel despondent and complacent?

PMID- 27702245
TI  - A cognitive-emotional model of NSSI: using emotion regulation and cognitive
      processes to explain why people self-injure.
AB  - Non-suicidal self-injury (NSSI) is a complex behaviour, routinely engaged for
      emotion regulatory purposes. As such, a number of theoretical accounts regarding
      the aetiology and maintenance of NSSI are grounded in models of emotion
      regulation; the role that cognition plays in the behaviour is less well known. In
      this paper, we summarise four models of emotion regulation that have repeatedly
      been related to NSSI and identify the core components across them. We then draw
      on social cognitive theory to unite models of cognition and models of emotion in
      developing a new cognitive-emotional model of NSSI. Our model articulates how
      emotion regulation and cognition can work in concert to govern NSSI, and offers
      several new research questions that can be addressed within this framework.

PMID- 27702246
TI  - From rhetoric to reality.
AB  - The rhetoric of public consultation features very strongly in recent documents on
      health and social care planning, but turning those good intentions into practice
      is not always straightforward. During 2001 I conducted a public consultation
      exercise for a local authority in the south of England as part of a Best Value
      review. Best Value is a process by which local authorities look systematically at
      their services with a view to ensuring that they are combining optimal outcomes
      with sensible economy, and public consultation is an essential element in the
      process.

PMID- 27702247
TI  - Identifying and assessing abuse in care homes - part 2.
AB  - Long-term care provides a regulated and important part of welfare support for
      thousands of older people. For some of these it will be a sanctuary from earlier
      mistreatment or neglect; for all residents it should provide security and good
      quality, dignified support in what is often their final home.

PMID- 27702249
TI  - Artificial feeding.
AB  - This year, one aspect of the RCN Mental Health and Older People Forum's strategy
      is to examine the practice of artificial feeding of people living with dementia.
      This is as a result of the concern expressed by many practitioners at study
      events throughout the year and from the highly emotive coverage in newspapers.

PMID- 27702248
TI  - Pressure sore prevention.
AB  - This article was presented in a clear and easy to understand manner and was
      therefore particularly helpful, not only in refreshing one's knowledge, but also
      in teaching care staff. I'm sure that when the care staff understand the
      importance of moving patients regularly, toileting them frequently, encouraging a
      well-balanced diet high in vitamins, protein and fibre, and drinking at least
      1500mls of fluid daily, this will not only contribute to the prevention of
      pressure problems but help to ensure each patient receives a high standard of
      care.

PMID- 27702250
TI  - Unmet need means pressures mount.
AB  - While the funding of long-term care continues to attract controversy around the
      UK, acute services for older people have grabbed the national headlines and
      fuelled debate in Westminster.

PMID- 27702251
TI  - Standing and moving: helping people with vascular dementia.
AB  - Aims and intended learning outcomes This article aims to explore ways in which
      people with vascular dementia can be helped to move. After reading this article
      you should be able to: ? discuss principles of safety in supporting movement ?
      understand the nature of cognitive and perceptual barriers to ovement ? explore
      techniques for overcoming specific difficulties.

PMID- 27702252
TI  - Faith and hope in charity.
AB  - As the government presses ahead with its plans for NHS reform, there has been
      growing speculation about the possibility of an increased role for the voluntary
      sector in the management and delivery of health care. According to one source (
      Hinscliff 2002 ), patients' groups are calling for a greater say in running
      hospitals, arguing that they possess the specialist skills required to ensure
      that services are patient-centred rather than organised for the convenience of
      staff. Such proposals are said to be attracting the interest of health secretary
      Alan Milburn, who is keen to incorporate patients' interests into the heart of
      the NHS following scandals such as those at the Bristol Royal Infirmary.

PMID- 27702253
TI  - Longer shift, better care?
AB  - Twelve-hour shifts are highly contentious in nursing, with mixed opinions about
      whether there are any real benefits for patients, staff or management. Research
      has highlighted issues such as tiredness, reduced teaching opportunities and even
      the possibility of a negative effect on staff recruitment ( Todd et al 1993,
      Turner et al 1987 ). However, our recent pilot study demonstrated potential
      benefits ( Bloodworth et al 2001 ). This article aims to take the debate a step
      further and suggests that 12-hour shifts can actually improve the implementation
      of the newNational Service Framework for Older People in a hospital setting ( DoH
      2001 ). We are aware that these are controversial arguments and hope to provoke
      thought and discussion.

PMID- 27702254
TI  - ?
AB  - Nurses are constantly required to imagine what patients are thinking or feeling
      in circumstances beyond their own experience. First-hand reports can help to
      increase awareness of potential patient needs. In this subjective account of a
      confusional state caused by acute renal failure, a retired psychiatrist (aged 79)
      recounts his own memories of being ill and attempts to relate them to events that
      occurred during his hospital stay.

PMID- 27702255
TI  - Statistics for people who (think they) hate statistics Neil J Salkind Statistics
      for People Who (Think They) Hate Statistics Sage 420 L24.99 076192776X 076192776X
      [Formula: see text].
AB  - Strong quantitative research methods are one of the patient's strongest
      safeguards against dangerous bias and prejudice on the part of researchers. In
      addition, the evidence that algorithmic decision making outperforms 'clinical' or
      other human decision making by a fair margin is very strong. It is therefore sad
      that statistics are so feared by students, and in general are not well taught.
      Most books are sound on the elementary parts of statistics, but start to become
      difficult when more abstract concepts are covered. This book is in that
      tradition.

PMID- 27702256
TI  - Practicing evaluation: a collaborative approach Rita O'Sullivan Practicing
      Evaluation: A Collaborative Approach Sage 200 L23 0761925465 0761925465 [Formula:
      see text].
AB  - This book is based on the author 's experience of undertaking evaluation across a
      variety of places and programmes, motivated by a desire to contribute to 'social
      service' programmes. The author promotes an approach called collaborative
      evaluation, which has similarities with participatory and empowerment evaluation.
      However, she suggests that this book demonstrates some 'novel variations' which
      should cause experienced evaluators to 'reflect on their practice ad the reasons
      they proceed in the manner they do'.

PMID- 27702257
TI  - How to manage your postgraduate course Lucinda Becker How to Manage Your
      Postgraduate Course Palgrave Macmillan 191 L12.99 140391656X 140391656X [Formula:
      see text].
AB  - This book is aimed at students who are new to postgraduate studies, whether they
      have just completed an undergraduate degree or have been in the workplace. It
      also attempts to address the whole range of postgraduate study, from a
      predominantly taught Masters course to a predominantly research-based doctorate.
      The author justifies this by noting that virtually all postgraduates will
      experience some research and some taught courses.

PMID- 27702258
TI  - Handbook of mental health in the workplace Jay C Thomas and Michel Hersen
      Handbook of mental health in the workplace Sage 574 L77 0761922555 0761922555
      [Formula: see text].
AB  - This book provides a comprehensive overview of theory, legislation (as it applies
      in the US) and good practice concerned with the successful employment of people
      with mental health disabilities.

PMID- 27702259
TI  - Interactive qualitative analysis: a systems method for qualitative research
      Norvell Northcutt Interactive Qualitative Analysis: A Systems Method for
      Qualitative Research and Danny McCoy Sage 464 L26.95 0761928340 0761928340
      [Formula: see text].
AB  - Both authors work at the University of Texas at Austin, and neither has a
      background in healthcare research. The stated aim of their text is to: 'help
      students unscramble the mysteries of qualitative data collection, coding and
      analysis...' And they propose using a 'systematic, qualitative technique:
      interactive qualitative analysis (IQA)'. There is a hint here that perhaps other
      approaches to qualitative analysis are not systematic, and that this is not a
      good thing.

PMID- 27702260
TI  - The essential guide to doing research Zina O'Leary The essential guide to doing
      research Sage 205 L18.99 0761941991 0761941991 [Formula: see text].
AB  - When a new book introducing readers to the research process is published, I ask
      myself why the need for another one and what is new about it. It certainly is a
      challenge for anyone writing on this subject in a market already saturated with
      textbooks aimed at helping students to do research.

PMID- 27702261
TI  - Evaluation: a systematic approach Peter Rossi Evaluation: A systematic approach
      et al Sage 470 L35 0761908943 0761908943 [Formula: see text].
AB  - This is the seventh edition of a much- referred-to classic text on programme
      evaluation. As the authors point out, when the book was first published in the
      l970s, evaluation of social programmes was not well-established - a situation
      which is very different now with evaluation research embedded throughout all
      types of public and non-public organisations and on a global basis. This makes
      the new edition a little less revolutionary, although a lot more useful.

PMID- 27702262
TI  - Qualitative Research: Theory, Method and Practice David Silverman Qualitative
      Research: Theory, Method and Practice Sage 390 L21.99 0761949348 0761949348
      [Formula: see text].
AB  - This book represents an extensive revision and updating of the 1997 first
      edition. It includes five new chapters commissioned for this volume. It is
      intended to be a comprehensive but accessible guide to 'a variety of
      methodological approaches to qualitative research'.

PMID- 27702263
TI  - Focus Group Practice Claudia Puchta and Jonathan Potter Focus Group Practice Sage
      L17.99 184 0761966919 0761966919 [Formula: see text].
AB  - Written by two experienced authors, this book is a useful addition to the
      literature addressing focus group practice. It relates specifically to managing
      the interaction which occurs within a focus group by examining conversation and
      discourse. Focus Group Practice does not aim to address issues of administration
      and planning of focus groups, as the authors feel that this has been adequately
      dealt with in other texts - although they do provide a brief overview of the
      history behind focus group practice.

PMID- 27702264
TI  - Reworking qualitative data Janet Heaton Reworking Qualitative Data Sage 176
      L18.99 0761971432 0761971432 [Formula: see text].
AB  - Reworking Qualitative Data is, to say the very least, an interesting and
      relatively novel text. For many nurse researchers (including me), this will be
      unfamiliar territory and a refreshing addition to the staple diet of research
      methodology books currently available. As the title suggests, the book explores
      the possibility and principles of undertaking secondary analysis of qualitative
      data sets. As the author acknowledges, secondary analysis of pre-existing
      statistical data sets has been commonplace for over the past 30 years, whereas
      the secondary analysis of qualitative data sets is still very much in its
      infancy. Given the novelty of this approach this book serves as a useful
      introduction for anyone considering the use of qualitative secondary analysis. It
      is packed with thought-provoking and interesting ideas and attempts to cover all
      the bases in terms of defining the methodology, discussing the types of
      qualitative secondary analysis, as well as attempting to grapple with the thorny
      epistemological and ethical and legal issues. The author even offers modi
      operandi for those wishing to undertake secondary analysis of a pre-existing data
      set.

PMID- 27702265
TI  - Introduction.

PMID- 27702267
TI  - SPSS in Practice Basant K Puri SPSS in Practice Arnold 175 L14.99 0340761121
      0340761121.

PMID- 27702268
TI  - Multi-professional Learning for Nurses Sally Glen Multi-professional Learning for
      Nurses and Tony Leiba Palgrave 153 L15.99 0333776380 0333776380.

PMID- 27702269
TI  - First Announcement and Call for Abstracts.

PMID- 27702270
TI  - An approach to the phenomenological analysis of data.
AB  - In this paper, Helena Priest describes and justifies a phenomenological research
      method that may be used to explore complex and nebulous concepts relevant to
      nursing and health care, for example, the concept of 'caring'. The history and
      development of Husserlian phenomenology are outlined, followed by an account of
      the use of phenomenology within nursing research. Tensions inherent in the use of
      Husserlian phenomenology in nursing research are noted. A phenomenological
      approach to data analysis, designed to address some of these tensions, is
      described and compared with several well-established phenomenological analysis
      strategies. Issues of reliability, validity and generalisability are discussed,
      as are limitations in the use of the approach, before conclusions relevant to
      healthcare researchers are drawn.

PMID- 27702271
TI  - Interaction as an ethically sensitive subject of research.
AB  - In this paper, Hanna Maijala, Paivi Astedt-Kurki and Eija Paavilainen discuss
      ethically sensitive family nursing research. A study of the interaction between
      caregivers and families expecting a child with an abnormality is used as an
      example: 29 parents and 22 caregivers were interviewed. Complementary data were
      obtained from essays written by five parents. This sensitive subject required
      discretion, especially when the parents were first asked to participate in the
      study, and during subsequent interviews. From the perspective of the data
      analysis, it was essential to obtain the informants' personal experiences
      unaltered. The constant comparative method of grounded theory was used to analyse
      the data. In the study findings, special attention was paid to presenting the
      results truthfully, while safeguarding the informants' anonymity. In conclusion,
      the ethical questions related to the subject of the study are discussed from the
      point of view of both the participant and the researcher.

PMID- 27702272
TI  - Commentary.
AB  - When I facilitate sessions that explore ethical aspects of research, one of the
      first activities I ask group members to do is to consider the rights which they
      believe they should have as potential research participants. Very quickly, and
      without exception, they are able to identify a range of issues from the right to
      confidentiality, through to freedom from harm and the right to know why the
      research is being undertaken. Given that these issues can so easily be
      identified, it could be tempting to assume that all research would be conducted
      in an ethical manner. Unfortunately, history reveals many horror stories of
      actions carried out in the name of research. Even today, questionable aspects of
      research are brought to light. The focus on research ethics within this edition
      of Nurse Researcher is thus a timely reminder of the key issues that need to be
      addressed.

PMID- 27702276
TI  - Illustrating the ethical dimensions of action research.

PMID- 27702278
TI  - The ethics of research with children.
AB  - In this article, the focus of which is research with children, Peter Allmark
      considers ethical issues in relation to both quantitative and qualitative
      research. Guidelines on the ethical conduct of research with children focus
      primarily on issues to do with quantitative research (e.g. RCPCH 2000 ). For this
      reason, this article tries to draw out points of particular importance to
      qualitative research. It begins with some assumptions and points of terminology,
      before briefly describing the history of the development of ethical regulation.
      It then discusses specific ethical issues that arise when researching with
      children. These are placed into three main categories: scientific validity,
      welfare, and rights and dignity.

PMID- 27702279
TI  - Editorial.
AB  - Ethical issues in research have, quite rightly, come under increasing scrutiny in
      recent years. In the UK, all research involving human subjects, patients, human
      samples, patient data, or NHS staff or facilities must take into account the
      requirements of the Research Governance Framework for Health and Social Care (
      DoH 2001 ). The Central Office for Research Ethics Committees (COREC), working on
      behalf of the Department of Health in England, co-ordinates the development of
      operational systems for Research Ethics Committees (RECs) in the NHS, and manages
      Multicentre Research Ethics Committees (MRECs) in England. Additionally, COREC
      now provides a strategic overview of Local Research Ethics Committees (LRECs). As
      part of their ethical review processes, LRECs will now require evidence of
      independent peer review, commensurate with the scale of the research. This will
      inevitably impact on the timescales for approval of projects, which should be
      taken into account when writing proposals and planning research. Recent guidance
      has included a definition of a research 'site': 'the geographical area covered by
      one Health Authority, whether the research is based in institution(s) or in the
      community', while multi-centre research is defined as: 'research taking place
      within the boundaries of two or more research "sites".' Other developments
      include changes affecting procedures to NHS Research Ethics Committees. Policy
      and guidance is continually developing and further information can be found on
      the Central Office for Research Ethics Committees' website:
      http://www.corec.org.uk/.

PMID- 27702280
TI  - Conferences.

PMID- 27702281
TI  - Royal college of nursing's annual international nursing research conference.
AB  - The Royal College of Nursing's annual international nursing research conference
      has gone from strength to strength in recent years, attracting around 400
      delegates. The event is organised under the auspices of the RCN Research Society,
      in partnership with their appointed RCN events manager and the RCN R&D Co
      ordinating Centre. Now an annual international event, there is a slow but steady
      increase in the number of international delegates. The principal aim of the
      conference is to share the best in nursing and health care research. It is always
      an excellent networking opportunity. A secondary aim is to nurture and support
      the next generation of researchers.

PMID- 27702285
TI  - Awards.

PMID- 27702284
TI  - The final hurdle: preparation for the phd viva examination.
AB  - The viva examination is the culmination of the PhD process. However, it is
      important to prepare carefully for this final and important hurdle. In this
      paper, Barbara Jack looks at the different stages of the viva examination, which
      include undertaking a careful and systematic preparation. This preparation
      involves gaining a comprehensive awareness of the university procedure for the
      viva, researching examiners, and considering the value of having a mock viva. The
      paper explores the actual viva and makes suggestions to deal effectively with
      questioning from the examiners. Finally, the results of the viva and steps needed
      to address corrections are discussed.

PMID- 27702286
TI  - ?

PMID- 27702288
TI  - Including the person with dementia in designing and delivering care Elizabeth
      Barnett Including the person with dementia in designing and delivering care
      Jessica Kingsley Publishers 223pp L14.95 1-85302-740-5 1853027405 [Formula: see
      text].
AB  - Essentially a case study, this book is divided into eight chapters and written in
      a very easy and accessible way, perhaps at the expense of adequate referencing.
      As the reader goes through the book a well-told story unfolds of the way the
      author attempted a detailed evaluation of certain aspects of care in one service
      for older people with dementia.

PMID- 27702289
TI  - The NHS Plan - funding nursing care.
AB  - The NHS Plan ( DoH 2000 ), published last year, emphasises improved care for
      older people. Key within it is the proposal that older people in all settings
      will receive free NHS nursing care by October this year. This is good news for
      older people living in nursing homes and who are at present paying for their
      nursing care. The Royal Commission on long term care ( 1999 ) recommended that
      all personal and nursing care should be funded, but this has been rejected by the
      government, which has said nursing care, but not personal care, will be free,
      thus creating an artificial divide between the two. As nurses who work with older
      people will know, integration of services and care approaches are necessary to
      maximise the older person's potential, and respond to their expressed needs and
      wishes.

PMID- 27702291
TI  - Website watch.
AB  - Useful websites on stroke care ?The Royal College of Physicians has produced a
      booklet aimed at providing information on stroke and stroke care for patients and
      their relatives. www.rcplondon.ac.uk/pubs/ceeu/strokecarecontents.htm.

PMID- 27702290
TI  - Avoiding another Lakeland.
AB  - In January the Commission for Health Improvement (CHI) revealed how the degrading
      treatment of older people with mental health problems had become common practice
      at one hospital unit in north Cumbria. Commissioners revealed a shocking culture
      of cruelty and neglect, including verbal abuse and patients tied to commodes
      while eating breakfast. How can such abuse still happen in the era of person
      centred care, not to mention basic human rights? More worryingly, to what extent
      does abuse still happen elsewhere?

PMID- 27702293
TI  - ?

PMID- 27702292
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27702294
TI  - Private care home owners lobby government.
AB  - Eight hundred banner-waving care home owners staged a mass lobby of parliament
      last month to protest at what they say is a 'crisis of care' caused by inadequate
      funding for the services they offer.

PMID- 27702295
TI  - Tough decisions ahead.
AB  - The government's response to the Royal Commission on long term care was published
      in July 2000 as part of the NHS Plan. Since then significant work has been
      undertaken in all four countries to develop the thinking further, particularly on
      the government's proposals for funding nursing care.

PMID- 27702296
TI  - Tissue oxygenation, perfusion, and position in patients with venous leg ulcers.
AB  - Inadequate oxygenation impairs the wound healing process, and so ensuring optimal
      delivery of oxygen to the tissues is likely to be an important issue in promoting
      the healing of venous leg ulcers. This study used a convenience sample of 31
      patients (with an age range of29to86years: mean age59.8years) who were attending
      vascular clinics on the west coast of the USA. Measurements indicated that
      control of peripheral circulation and tissue oxygenation may be impaired in
      people with venous ulcers. Leg elevation, sitting and standing decreased wound
      perfusion, and so the authors suggest that more research is necessary to
      investigate these relationships in more detail. 53 references.

PMID- 27702297
TI  - The relationship of hardiness and depression to disability in institutionalized
      older adults.
AB  - Studies of depression among residents of long term care facilities are a familiar
      component of the research literature, but the concept of 'hardiness' is less
      familiar on this side of the Atlantic. Studies have suggested that health-related
      hardiness predicted the degree of disability experienced by older people
      subjected to similar levels of stress. In this study, a lecturer at Yale
      University explored the relationship of hardiness and depression to disability in
      a sample of 58 older people who were residents in a nursing home. The results
      indicated that the psychological variables of hardiness and depression
      contributed more than did health status and length of stay to explaining levels
      of disability. The author concludes by suggesting therapeutic approaches which
      may be beneficial. 56 references.

PMID- 27702298
TI  - Practice guide for pain management in people with dementia in institutional care
      (and facilitator's book) Dr W McClean Practice guide for pain management in
      people with dementia in institutional care (and facilitator's book) The
      University of Stirling Dementia Services Development Centre (Tel: 01786 467740)
      L14 for both publications 36pp (Facilitators Book 40pp) 1-85769-0293 1857690293.
AB  - This is another excellent offering from the University of Stirling which helps to
      explore the issue of pain both in older people and older people living with
      dementia. Although clearly targeted as a package of learning for those with
      limited experience in this field, the practice guide will have something for most
      practitioners.

PMID- 27702299
TI  - A team education project: an evaluation of a collaborative education and practice
      development in a continuing care unit for older people.
AB  - The aim of this team education project was 'to provide multidisciplinary
      education in the clinical environment and to directly influence practice'. The
      education programme was carried out in a continuing care unit for older people
      situated in inner London. The education programme consisted of twice-weekly, ward
      based reflective groups held over seven weeks. The theme chosen for exploration
      in the group was that of bereavement. Although the intention had been to include
      participants from a wide range of backgrounds, there proved to be little
      involvement from non-nursing staff. The evaluation interviews conducted with
      group members were generally positive, but all the interviewees said that the
      programme had not changed the way they worked with residents. The authors argue
      that a psychoanalytic approach is useful when studying organisational behaviour
      in a stressful environment. 26 references.

PMID- 27702303
TI  - ?

PMID- 27702302
TI  - ?
AB  - I work on a trauma/orthopaedic ward. My aim is to produce a patient information
      leaflet on preventing constipation in hospital. Does anyone use a similar
      leaflet, or have any advice to offer? Any information would be appreciated.

PMID- 27702304
TI  - ?

PMID- 27702307
TI  - News in Brief Rehabilitation and Remedial Services for available L20 from the
      Audit Commission on 0800 502030. 1-86240-221-3 1862402213.
AB  - A roundup of the latest nursing news.

PMID- 27702306
TI  - ?

PMID- 27702308
TI  - ?
AB  - Maureen O'Neill, Director of Age Concern Scotland and Lord McCluskey, newly
      appointed chairman, unveiling a poster campaign to publicise a new helpline (0808
      808 8141) to combat elder abuse.

PMID- 27702309
TI  - Pilot sites chosen for new dementia care service.
AB  - Six pilot sites have won funding from the Mental Health Foundation to develop a
      new dementia service project which aims to support people in the early stages of
      the disease living in their own homes.

PMID- 27702310
TI  - Older adults' descriptions of hope after a stroke.
AB  - The experiences of a convenience sample of nine stroke survivors drawn from a
      local stroke support group formed the basis of this American study. The two
      research questions were (i) what are the patterns of hope manifested by older
      adults after a stroke? and (ii) what are the factors associated with their
      patterns of hope after the stroke? Some of the hope themes which emerged from
      analysis of the transcripts, such as 'positive anticipation' and 'faith in God',
      have been previously identified by earlier researchers. Other themes, such as
      'previous abilities' and 'mobility' are claimed to be missing from the (mostly
      American) literature on hope. As one survivor said, 'I hoped I would be able to
      move and feel like I used to do'. 73 references.

PMID- 27702312
TI  - Response to the Letter.

PMID- 27702311
TI  - Assessment seminars.
AB  - The assessment of individuals for health and/or social care can often result in
      older people being wrongly placed in residential care when nursing care is
      required. The RCN has lobbied consistently for comprehensive assessment leading
      to appropriate care from a range of professionals for all older people who often
      have inter-related health and social care needs. Unfortunately, nursing's
      holistic nature can be undermined by managers and service providers who seek to
      contain costs, even though nurses' distinct contribution to the overall care of
      older people is cost-effective and can result in significant positive patient
      outcomes.

PMID- 27702313
TI  - CORRIGENDA.

PMID- 27702314
TI  - Response to the letter by Sugiyama and Oda.

PMID- 27702316
TI  - ERRATUM.

PMID- 27702315
TI  - Letter to the Editor: Vitamin D Deficiency and Fractures in Children: A
      Mechanistic Point of View.

PMID- 27702318
TI  - In Vitro Activation: A Dip Into the Primordial Follicle Pool?
AB  - CONTEXT: A current limitation of assisted reproduction is the number of available
      female gametes. This Commentary discusses in vitro activation (IVA), a technique
      that activates dormant ovarian follicles so that these follicles can become
      mature oocytes for fertilization. There is considerable evidence that mechanical
      signaling plays an important role in oocyte maturation and survival; manipulation
      of the mechanical environment is a key component of the IVA process. IVA acts on
      existing follicles and does not promote neo-oogenesis, which likely contributes
      little to the primordial follicle pool in the adult. CONCLUSIONS: Several women
      with primary ovarian insufficiency who underwent the IVA procedure have achieved
      live births. IVA might also be applicable to women with pathological diminished
      ovarian reserve and those with physiological diminished reserve due to natural
      aging. Cancer patients with cryopreserved ovarian tissue also might benefit from
      IVA. Based on future studies, IVA could prove to be a revolutionary tool for
      assisted reproduction.

PMID- 27702320
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27702319
TI  - Letter to the Editor: Hypothyroidism Following Hemithyroidectomy: Incidence, Risk
      Factors, and Clinical Characteristics (Ahn D, Sohn JH, Jeon JH. Hypothyroidism
      following hemithyroidectomy: Incidence, risk factors, and clinical
      characteristics. J Clin Endocrinol Metab. 2016;101(4):1429-1436.).

PMID- 27702321
TI  - Still rockin'!

PMID- 27702322
TI  - New ways of rocking into older age.
AB  - Elvis Presley is currently appearing in our local nursing home. Well, actually
      he's an impersonator and the residents don't find him particularly authentic, but
      he's willing to do domiciliary performances and his fees can be met within the
      activities budget.

PMID- 27702323
TI  - ?
AB  - I found the article 'Assessment of older people using medication' (October 2001)
      to be interesting and very informative. As an anticoagulant nurse, the vast
      majority of the patients I deal with are over 65. I have always emphasised the
      importance of patient education, assessment and consent in treatment and therapy.

PMID- 27702325
TI  - Trained to care Gillian Dalley Trained to care , Michael Denniss , editors Centre
      for Policy on Ageing L15 + L1.25 p&p 1 901097 60 9 1901097609.
AB  - This book is a report on the outcomes of a study which investigated the skills
      and competencies of care assistants in homes for older people. I found it to be a
      factual account of present practice, and a timely publication in relation to the
      new legislative requirements within the long-term care sector.

PMID- 27702327
TI  - ?
AB  - There is now a welcome focus on health education topics of relevance to older
      people. In this study using semi-structured interviews, 20 men and women between
      the ages of 58 and 87, who attended an Age Concern day centre, were asked for
      their views on skin cancer. The results indicated limited knowledge of how to
      carry out skin self-examination, and a low sense of personal susceptibility to
      the disease. The authors conclude with a discussion of the way in which health
      education targeted at older people needs to take into account age-specific health
      beliefs, and ethical issues which are appropriate for all age groups. 29
      references.

PMID- 27702328
TI  - ?
AB  - This timely paper reflects the focus on person-centred care which has become the
      dominant philosophy in settings that care for people with dementia, and has been
      taken up in the recent National Service Framework document. Using the dementia
      care mapping approach developed by Tom Kitwood and his team, an audit was
      conducted in six in-patient units and six day-care facilities operated by one NHS
      Trust.

PMID- 27702329
TI  - Journal scan.
AB  - In this study, a grounded theory approach was used in order to explore concepts
      relating to the subject of 'hope' in the context of a continuing care ward. The
      sample consisted of five registered mental health nurses, who all worked on the
      same hospital ward in the north of England. Semi-structured interviews were used
      to elicit the key concepts utilised by the participants, and analysis of the
      transcripts identified four core variables: a humanistic code (treating clients
      as individuals); pragmatic knowledge (specific interventions); interpersonal
      relations (human interaction); and the nurse as a utilizer (organisational
      skill). The issue of hope held major importance. As one of the nurses said, 'When
      I start to feel a little hopeless myself, I make sure that this is not
      communicated to the client'. 64 references.

PMID- 27702330
TI  - Voices in the valleys.
AB  - In Wales, as throughout Britain, older people were looking forward to October 1 -
      the day the government promised free long-term care. But everywhere they have
      been let down. Older people clearly feel they are entitled to free care through
      the National Insurance contributions they have paid, and here in Wales, Age
      Concern Cymru (ACC) is asking for all personal and nursing care to be provided
      free to older people, funded from taxation.

PMID- 27702331
TI  - Life and death in English nursing homes: sequestration or transition?
AB  - Issues surrounding death and dying are now beginning to receive both serious
      attention from researchers in a range of disciplines, and support from those
      organisations which fund research. This study represents an appropriate extension
      of this research agenda to the environment of the nursing home. Participant
      observation was employed to gather data in four nursing homes over a period of
      411 hours. One theme to emerge was the difficulty all experienced in identifying
      with any clarity a distinct 'dying role'.

PMID- 27702332
TI  - Campaigners combine to sign charter on rights for older people.
AB  - Twenty charities and other campaigning groups, including the RCN, joined forces
      last month to launch the Right to Care Charter, which calls on the government to
      fund all nursing and personal care free at the point of use.

PMID- 27702333
TI  - Involving older people.
AB  - The RCN Gerontological Nursing Programme (GNP) is involved in a wide range of
      practice development projects within the independent sector and the NHS. These
      focus on developing person-centred care through the transformation of cultures
      and attitudes to older people. Practice development involves focusing on
      practitioners' learning within the workplace and utilises a range of activities.

PMID- 27702334
TI  - New publications.

PMID- 27702336
TI  - Warning over nursing home places.
AB  - A huge expansion will be needed in the number of nursing and residential home
      placements if the UK is to keep pace with demographic changes, the Office for
      National Statistics has reported.

PMID- 27702335
TI  - ?
AB  - I read with interest the continuing professional development article on skin care
      (November). Although mostly excellent, I would just like to point out that greasy
      emollients such as white soft paraffin/liquid paraffin 50/50 or zinc and castor
      oil are not recommended for use with incontinence pads. This is because the
      'barrier' effect, while supposedly protecting the skin, also forms a moisture
      resistant layer on the surface of the pad which prevents the absorption process,
      and can therefore have the opposite effect of making the skin wetter and more
      prone to soreness.

PMID- 27702337
TI  - Getting in touch.
AB  - High on our strategy agenda is an improvement in communication among forum
      members and we are happy to be contacted via email. This is especially relevant
      now as planning for next year's congress is underway.

PMID- 27702339
TI  - Forum for Nurses Working with Older People.
AB  - Priority issues for our forum's strategy next year include NHS-funded nursing
      care, care home closures, downgrading of pensions and entry into nursing homes
      and intermediate care.

PMID- 27702340
TI  - RCN Mental Health and Older People Forum.
AB  - Members of the Mental Health and Older People Forum are keen to make themselves
      even more accessible and 'open for business' next year. Strategically, this
      means.

PMID- 27702342
TI  - Changing chairs.
AB  - Rosemary Strange, chair of the Forum for Nurses working with Older People, and
      Sharon Blackburn, chair of the Mental Health and Older People Forum, will not be
      standing for re-election this month. Both steering committees and the forums
      express their sincere thanks to both for their sound leadership and considerable
      hard work in recent years.

PMID- 27702341
TI  - Discharging responsibilities.
AB  - In February the House of Commons health committee began to hear oral evidence as
      part of its investigation of delayed hospital discharges. For many people, such a
      step is to be welcomed and is probably even long overdue. After all, official
      monitoring processes suggest that between 5,000 and 7,000 older people may be
      experiencing delayed hospital discharges at any one time.

PMID- 27702344
TI  - Preparing for congress.
AB  - The forums are preparing for this month's RCN Congress 2002. Look out for their
      educational event on the nurse's role in assessment, in collaboration with the
      RCN Gerontological Nursing Programme.

PMID- 27702345
TI  - Older people 'failed by mental health services'.
AB  - Mental health care for older people is inconsistent, with many areas failing to
      meet the requirements of the National Service Framework for Older People,
      according to a government watchdog.

PMID- 27702346
TI  - From rhetoric to reality.
AB  - A consultation exercise on the future of services for older people which I
      undertook recently for a local authority social services committee, revealed -
      predictably - a wide diversity of opinions. But there were deep variations, too,
      in the abilities of the stakeholders we were consulting to put across their
      points of view, and I saw it as an important part of my role to try to compensate
      for these differences when listening to people who clearly had difficulties in
      communication. Carers and relatives, groups who often go unheard, were, in this
      situation, both articulate and in most cases well-organised. I had only to
      advertise my availability for their point of view to be expressed powerfully, by
      individuals and groups, orally and in writing, some of it moderately expressed,
      some of it put across with passion, even anger.

PMID- 27702347
TI  - Infection control.
AB  - This article emphasised that older people are at increased risk of infection when
      they have illnesses such as diabetes, are on medications like steroids and in
      settings where residents live closely together and infection can spread.

PMID- 27702348
TI  - Secure environments.
AB  - One of the key elements of the strategy of the Mental Health and Older People
      Forum for 2001-02 was to look at the needs of older people who are being cared
      for in secure environments. This has proved to be a difficult issue to explore,
      as there appears to be a limited amount of information readily available.

PMID- 27702349
TI  - Feeding into the RCN strategy.
AB  - Issues in the mental health care of older people do not remain static for long.
      One moment you have set out a baseline standard for assessing X, Y or Z and the
      following day there is an entry in a journal suggesting that this baseline is
      already out of date!

PMID- 27702350
TI  - ?
AB  - Staff drawn from 15 nursing homes in Hillsborough County, Florida, formed the
      sample for this study. Questionnaire data provided demographic and managerial
      information. This indicated that the turnover rate in the previous six months was
      23 per cent, while for nursing assistants it was 45 per cent. Selected staff
      members from each nursing home were then asked to consider six previously
      developed case studies which had been designed to illustrate aspects of autonomy.
      Certified nursing assistants were more likely than registered nurses to believe
      that it is the home's responsibility to make choices for residents. 15
      references.

PMID- 27702352
TI  - ?
AB  - A purposive sample of ten nurses working in an orthopaedic unit in eastern Canada
      were interviewed in order to explore their experiences of caring for older people
      suffering from acute confusion. All subjects reported that acute confusion was a
      'regular occurrence', and that it is much worse in the evening and at night. The
      three strategies used for coping when patients became unmanageable and disruptive
      were sitters, medication and physical restraint. The latter was regarded as a
      last resort and would only be implemented with the permission of the patient's
      family.

PMID- 27702351
TI  - Learning by degrees.
AB  - The National Service Framework for Older People (DoH 2001a) clearly sets out the
      government's strategic intentions for the development of services to meet the
      health and social care needs of older people. In order to make these plans a
      reality, not only are fundamental changes required in the way health and social
      services are organised and delivered but also in the way in which nurses and
      allied health professionals are educated.

PMID- 27702353
TI  - Plans for networking.
AB  - A key area of development for the committee in 2002 is to continue to promote
      awareness of the mental health needs of older people within the RCN as an
      organisation and to link with other individuals and agencies with an interest in
      the area.

PMID- 27702354
TI  - How the other half lives.
AB  - If I need an extra shift to supplement my wage I volunteer to work as a carer in
      the nursing home. I am still paid as a staff nurse but perform care assistant
      duties. Both nurses and carers are there to work together to meet patients' daily
      living, nursing, emotional and social needs so, in that sense, there is little
      difference. In fact I enjoy the freedom away from drug rounds, wound management
      and administration duties. I can get back to the heart of nursing: delivering
      direct care to patients.

PMID- 27702355
TI  - Government pledges extra funding to boost intermediate care.
AB  - The government has pledged L66 million in extra funding to help provide more
      intermediate care for older people.

PMID- 27702356
TI  - Major role for nurses in assessment guidance.
AB  - Nurses are poised to play a central role in the implementation of new guidance
      issued by the Department of Health to help health and social care agencies
      develop a single assessment process for older people.

PMID- 27702360
TI  - Primary Care and Dementia Primary Care and Dementia Steve Iliffe and Vari Drennan
      Jessica Kingsley 155pp L13.95 1 85302 997 1 1853029971.
AB  - This recent addition to the Bradford Dementia Group's Good Practice Guides offers
      a very practical handbook to the practitioner within primary care. It is
      ostensibly aimed at general practitioners seeking to offer a fully inclusive
      service with advice on diagnosis, routes through treatment and care and
      suggestions around support services and liaison.

PMID- 27702361
TI  - ?
AB  - Residents at Gloucester House, a nursing home in Sevenoaks, Kent, have been
      learning to use a newly purchased computer with the help of pupils from a local
      school who are undertaking a community services programme. Various aids and add
      ons have been acquired to make the computer accessible to as many residents as
      possible. They can use the equipment to surf the internet, email friends and
      family, and pursue other hobbies and interests. Pictured with Gloucester House
      resident Charity McLaughlan, are Richard Challis, a student at Sevenoaks School,
      and Colin Seaward, chair of the Friends of Gloucester House.

PMID- 27702357
TI  - Misguided attitudes bar progress.
AB  - There was a former prison officer on a long-stay ward for older people where I
      once worked who was so implacably opposed to change and so firmly entrenched in
      odd little routines that if some minute alteration to the day-to-day running of
      the place was proposed by staff, it was easier to avoid telling him and facing
      his inevitable opposition than to go ahead and act. We would consult the others,
      not with any confidence that they understood, but more from a sense of duty. Then
      we would do the deed - weekend trips to the coast, for example, or something
      radical like re-arranging the day room - and then brave the huffing that would
      persist until the prison man acclimatised to the new arrangements.

PMID- 27702362
TI  - John Adams scans a range of journals and highlights their relevance for nurses
      who work with older people.
AB  - In this Canadian study, staff and residents from three long-term care facilities
      were asked for their opinions on the issue of mobility in such an environment.
      Focus group methods were used to collect the data.

PMID- 27702363
TI  - New publications.
AB  - Good Practice with Vulnerable Adults Jackie Pritchard, editor Jessica Kingsley
      Publishers L16.95 ISBN 1 85302 982 3 A practical trans-disciplinary guide for
      professionals which looks at key problems and dilemmas in protecting vulnerable
      adults from abuse. The content covers the procedural implications of the latest
      Department of Health guidance on working with vulnerable adults.

PMID- 27702364
TI  - ?
AB  - Letters to the Editor are welcome. Send to The Editor, Nursing Older People, 17
      19 Peterborough Road, Harrow, Middlesex HA1 2AX. We reserve the right to edit
      letters.

PMID- 27702365
TI  - Website watch.

PMID- 27702366
TI  - Still Rockin.

PMID- 27702367
TI  - Events.
AB  - April 19 Medication and Older People - study day Age Concern, The National
      Council of Ageing Venue: Marlgrove Club, Bromsgrove. Fee: L59 Contact: Graham
      Steele, Age Concern Training, Martindale, Hawks Green Lane, Hawks Green, Cannock,
      Staffordshire WS11 2XN. Tel: 01543 503660. Fax: 01543 504640. Email:
      steeleg@ace.org.uk.

PMID- 27702368
TI  - Out to pasture?
AB  - Nursing homes can provide space for the development of creative and dynamic
      nursing practice that should be celebrated. However, there is no doubt that
      negative attitudes towards nursing homes and the nurses who work in them persist.
      Comments such as 'what do you do all day, do you it drinking tea?' or 'isn't it
      depressing?' are common, and the opinion that nurses working in this setting
      'probably couldn't get a job anywhere else' tends to be held by those who have
      never set foot inside a nursing home.

PMID- 27702369
TI  - New publications.
AB  - Factors affecting demand for primary health care services by residents in nursing
      homes and residential care homes Charles Crosby, Keith Edward Evans and Lesley
      Ann Prendergast 140pp L39.95 ISBN 0-7734-7627-X Investigates the demand for
      general practice and community nursing services in an area with a high
      concentration of care homes. Shows that there is a large overlap between nursing
      and residential homes in dependency levels of residents.

PMID- 27702371
TI  - ?
AB  - Two large-scale studies commissioned by the Department of Health, one a
      longitudinal survey of people aged 65 or over admitted to residential and nursing
      homes, and the other a cross- sectional survey of homes for older people, formed
      the basis of this study. A detailed picture of care provision for older people
      with cognitive impairment is provided. Very few residents left care homes
      permanently after admission. Only 2 per cent had been discharged by 30 months
      after admission. Another important finding concerns mortality. About one third of
      the sample had died by six months after admission, while by 30 months almost two
      thirds had died. Overall the median length of stay of publicly funded residents
      was 18 months. 24 references.

PMID- 27702373
TI  - Community Care of Older People Beales David Denham Michael Tulloch Alistair
      Community Care of Older People editors 206pp L18.95 1 85775 032 2 1857750322.
AB  - The title suggests that this book offers a range of perspectives on the care of
      older people in 'thecommunity'. Chapters include broad coverage of, for example,
      the biol-ogy and demography of older age, physical and mental disease in older
      people, prescribing, nutrition, screening and assessment, health promotion,
      anticipatory and institu-tional care and ethics.

PMID- 27702372
TI  - Older People and Their Needs: A Multi-disciplinary Perspective Gianetta Corley ,
      Editor Whurr Publishers 221pp L19.50 1 86156 083 4 1861560834.
AB  - Fourteen relatively short chapters make up this informative and very readable
      text aimed at professionals and experienced family carers. The wide range of
      topics, covering physical, psychosocial, religious and financial issues reflect
      the diversity of older people's needs and the expertise required to meet them.
      The chapters on nutrition and foot care are excellent and serve as reminders for
      good practice in assessment and ongoing care. Insights into the theoretical
      frameworks and methods of working by close team colleagues such as physios and
      occupational therapists are enlightening. The most thought provoking chapters
      include personal accounts and case studies, for example those on working with
      families, the quality of services for people with dementia and the work of the
      chaplain.

PMID- 27702374
TI  - Website watch.
AB  - ? Net Doctor has a helpful site on the fundamentals of tubercu- losis, with
      questions and answers explaining the disease, which parts of the body it affects,
      how it is caught, symptoms and how it develops.
      www.netdoctor.co.uk/diseases/facts/tuberculosis.htm.

PMID- 27702375
TI  - Still Rockin'!

PMID- 27702376
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27702377
TI  - Collaboration, facilities and communities in day care services for older people.
AB  - Similarities and differences between day hospitals, run by the NHS, and day
      centres, run by local authorities or charitable organisations, have been widely
      discussed in the literature of gerontology for many years. The authors of this
      paper have undertaken a single blind, randomised-controlled trial to compare
      rehabilitation outcomes in the two settings, which was published in 1999. This
      research project involved augmenting the staff of day centres by visiting
      therapists. In addition to quantitative findings, their project also generated
      much qualitative data from interviews with health service and social service
      staff which provides the thought-provoking content. The themes identified
      included the reluctance of some patients to accept referral to a day centre, and
      the difficulties associated with discharging patients. Positive aspects included
      the opportunity to share skills, knowledge and resources. 29 references.

PMID- 27702379
TI  - Basic needs of older people in hospital 'often ignored'.
AB  - Older people and their carers are the least satisfied of all groups with the care
      they receive from the NHS when they are acutely ill, according to a report by an
      expert nursing group, which says care is often deficient in fundamental aspects
      of nursing.

PMID- 27702380
TI  - ?
AB  - We are a group of intermediate care clinical leaders who are keen to establish a
      way of monitoring the capacity of the five intermediate care teams that have been
      set up in Leeds. We are aware of some tools that have been developed for district
      nursing but have found that the complexities of the workload and the
      interdisciplinary nature of intermediate care make the tools very difficult to
      adapt for our use. We would be keen to make contact with any colleagues who are
      grappling with the same issues, or indeed have developed a tool that works for
      them. It would also be good to share the experience that we have with others
      involved in this exciting, developing area of service provision.

PMID- 27702381
TI  - ?
AB  - The Royal College of Nursing Gerontological Nursing Programme is compiling a
      database of nurses in the United Kingdom and Eire who are using the RCN
      Assessment Tool for older people. This database could be used for nurses using
      the tool to network with each other, share issues and keep nurses in touch with
      any developments regarding the tool.

PMID- 27702382
TI  - ?
AB  - We are staff nurses at a 19-bedded nursing home. We were recently looking at our
      dependency scores and discovered anomalies, with patients of different dependency
      achieving similar scores.

PMID- 27702383
TI  - Assessing admirals.
AB  - The Admiral nurses and Royal College of Nursing Gerontological Nursing Programme
      competencies project began in August 2000 and is a part-time, 20-month project
      funded by the Dementia Relief Trust. Admiral nurses are specialist dementia care
      nurses and the Dementia Relief Trust is a charity which supports their work.
      Admiral nurses' casework supports those providing care for people with dementia
      living in the community. In their consultancy and teaching role, Admiral nurses
      promote good practice in dementia care. They work in different care settings and
      in total there are 12 Admiral nurse services.

PMID- 27702384
TI  - Mental health and older people.
AB  - Much has been written in recent months about the issues associated with the long
      term care of older people and the funding of nursing care. Some may even think
      that they have read and heard more than enough. However, the policy and practice
      group of the RCN Forum for Older People and Mental Health believes it is an issue
      that cannot be ignored and that nursing care should be free at the point of
      delivery irrespective of where it is delivered.

PMID- 27702385
TI  - An Admiral nurse's experience of the project.
AB  - The first time I came across the project was six months ago, my first day as an
      Admiral nurse. This was at a study day at the Dementia Relief Trust. Vicki
      explained how it would examine the ways Admiral nurses were working at higher
      competency. The first stage in this was for Vicki to look at the work Admiral
      nurses did and by observing and interviewing them to break the work down into
      different discernible parts (or competencies).

PMID- 27702386
TI  - New framework will 'root out age discrimination'.
AB  - A new national blueprint for the care of older people in England was finally
      launched last month amid government claims that it would tackle age
      discrimination and drive up standards.

PMID- 27702387
TI  - A brighter future for older people.
AB  - There was a cartoon in a recent issue of Private Eye in which a doctor was
      telling an older woman: 'Under the new charter, elderly patients will not be
      treated differently by the NHS - they'll be treated just as badly as everyone
      else.' If you overlooked the fact that the woman's slightly dotty hat and nervous
      clutching of her handbag were the cartoonist's clumsy way of indicating her
      advancing years, there was a certain ironic wit in the caricature.

PMID- 27702389
TI  - Editorial.

PMID- 27702390
TI  - Can emotional content reduce the age gap in visual working memory? Evidence from
      two tasks.
AB  - Ageing is associated with declines in several cognitive abilities including
      working memory (WM). The goal of the present study was to assess whether
      emotional information could reduce the age gap in the quantity and quality
      (precision) of representations in visual WM. Young and older adults completed a
      serial image recognition (SIR) task and a colour-image binding (CIB) task.
      Results of the SIR task showed worse performance for negative than neutral and
      positive images within the older group, hence enlarging the age gap in WM. In the
      CIB task, recall precision was lower in the old than young adults, showing an
      ageing decline in the quality of WM representations. Positive images tended to
      improve precision, but this boost was similar for both age groups. In sum,
      emotional content did not reduce the age gap in visual WM.

PMID- 27702388
TI  - Epidermal Growth Factor Induces Proliferation of Hair Follicle-Derived
      Mesenchymal Stem Cells Through Epidermal Growth Factor Receptor-Mediated
      Activation of ERK and AKT Signaling Pathways Associated with Upregulation of
      Cyclin D1 and Downregulation of p16.
AB  - The maintenance of highly proliferative capacity and full differentiation
      potential is a necessary step in the initiation of stem cell-based regenerative
      medicine. Our recent study showed that epidermal growth factor (EGF)
      significantly enhanced hair follicle-derived mesenchymal stem cell (HF-MSC)
      proliferation while maintaining the multilineage differentiation potentials.
      However, the underlying mechanism remains unclear. Herein, we investigated the
      role of EGF in HF-MSC proliferation. HF-MSCs were isolated and cultured with or
      without EGF. Immunofluorescence staining, flow cytometry, cytochemistry, and
      western blotting were used to assess proliferation, cell signaling pathways
      related to the EGF receptor (EGFR), and cell cycle progression. HF-MSCs exhibited
      surface markers of mesenchymal stem cells and displayed trilineage
      differentiation potentials toward adipocytes, chondrocytes, and osteoblasts. EGF
      significantly increased HF-MSC proliferation as well as EGFR, ERK1/2, and AKT
      phosphorylation (p-EGFR, p-ERK1/2, and p-AKT) in a time- and dose-dependent
      manner, but not STAT3 phosphorylation. EGFR inhibitor (AG1478), PI3K-AKT
      inhibitor (LY294002), ERK inhibitor (U0126), and STAT3 inhibitor (STA-21)
      significantly blocked EGF-induced HF-MSC proliferation. Moreover, AG1478,
      LY294002, and U0126 significantly decreased p-EGFR, p-AKT, and p-ERK1/2
      expression. EGF shifted HF-MSCs at the G1 phase to the S and G2 phase.
      Concomitantly, cyclinD1, phosphorylated Rb, and E2F1expression increased, while
      that of p16 decreased. In conclusion, EGF induces HF-MSC proliferation through
      the EGFR/ERK and AKT pathways, but not through STAT-3. The G1/S transition was
      stimulated by upregulation of cyclinD1 and inhibition of p16 expression.

PMID- 27702391
TI  - Affect, Attachment, Memory: Contributions Toward Psychobiologic Integration.

PMID- 27702392
TI  - Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in
      Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Selenium supplementation may decrease circulating thyroid
      autoantibodies in patients with chronic autoimmune thyroiditis (AIT), but the
      available trials are heterogenous. This study expands and critically reappraises
      the knowledge on this topic. METHODS: A literature search identified 3366
      records. Controlled trials in adults (>=18 years of age) with AIT, comparing
      selenium with or without levothyroxine (LT4), versus placebo and/or LT4, were
      eligible. Assessed outcomes were serum thyroid peroxidase (TPOAb) and
      thyroglobulin (TgAb) autoantibody levels, and immunomodulatory effects. After
      screening and full-text assessment, 16 controlled trials were included in the
      systematic review. Random-effects meta-analyses in weighted mean difference (WMD)
      were performed for 3, 6, and 12 months of supplementation in two different
      populations: one receiving LT4 therapy and one newly diagnosed and LT4-untreated.
      Heterogeneity was estimated using I2, and quality of evidence was assessed per
      outcome, using the Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) guidelines. RESULTS: In LT4-treated populations, the selenium
      group had significantly lower TPOAb levels after three months (seven studies: WMD
      = -271 [confidence interval (CI) -366 to -175]; p < 0.0001; I2 = 45.4%), which
      was consistent at six months (three studies) and 12 months (one study). TgAb
      decreased at 12 months, but not at three or six months. In LT4-untreated
      populations, the selenium group showed a decrease in TPOAb levels after three
      months (three studies: WMD = -512 [CI -626 to -398]; p < 0.0001, I2 = 0.0%), but
      not after 6 or 12 months. TgAb decreased at 3 months, but not at 6 or 12 months.
      Quality of evidence was generally assessed as low. Study participants receiving
      selenium had a significantly higher risk than controls of reporting adverse
      effects (p = 0.036). CONCLUSIONS: Selenium supplementation reduced serum TPOAb
      levels after 3, 6, and 12 months in an LT4-treated AIT population, and after
      three months in an untreated AIT population. Whether these effects correlate with
      clinically relevant measures remains to be demonstrated.

PMID- 27702393
TI  - Sex-Comparative Analysis of the miRNome of Human Amniotic Mesenchymal Stem Cells
      During Obesity.

PMID- 27702394
TI  - Dynamic microRNAome profiles in the developing porcine liver.
AB  - Increasing evidence suggests that micro (mi)RNAs play important roles in various
      biological process. To evaluate the roles of miRNA in the porcine liver, we
      investigated the dynamic profiles of microRNAomes using liver tissue from pigs
      during the embryonic period (embryonic day 90), weaning stage (postnatal day 30),
      and adult stage (7 years old). A total of 186 unique miRNAs were differentially
      expressed during liver development. We also identified that 17, 13, and 6 miRNAs
      were specifically abundant at embryonic day 90, postnatal day 30, and at 7 years,
      respectively. Besides regulating basic cellular roles in development, miRNAs
      expressed at the three developmental stages also participated in regulating
      "embryonic liver development," "early hepatic growth and generating a functioning
      liver," and "energy metabolic processes," respectively. Our study indicates that
      miRNAs are extensively involved in liver development, and provides a valuable
      resource for the further elucidation of miRNA regulatory roles during liver
      development.

PMID- 27702395
TI  - Identification and quantification of adulteration in Garcinia cambogia commercial
      products by chromatographic and spectrometric methods.
AB  - Species of genus Garcinia are rich sources of bioactive constituents with
      antimicrobial, anticancer, anti-inflammatory, hepatoprotective and anti-HIV
      activities. Commercial products of Garcinia cambogia are used as anti-obesity
      drugs with increasing market demand. Because of the high price of its products,
      it can be adulterated with similar lower-priced species. This study was designed
      to develop and validate an accurate and efficient method for the detection of any
      adulteration (G. indica) in G. cambogia products. For this purpose, high
      performance liquid chromatography (HPLC) was used to analyse the ethanolic fruit
      rind extracts of G. cambogia and G. indica, their formulations of 0.5, 1, 2, 5,
      10, 20, 30, 40, 50, 60, 70, 80, 90 and 95% G. indica with G. cambogia, and 11 G.
      cambogia commercial products. The analytical methods were validated by quality
      assurance parameters of linearity, sensitivity, precision and accuracy. Two
      marker peaks were detected in G. indica fruit extract, whereas G. cambogia did
      not show these peaks. The detected peaks were identified as anthocyanins;
      cyanidin-3-O-sambubioside and cyanidin-3-O-glucoside. In the study to determine
      the effect of pH and temperature on the stability of its anthocyanin content,
      HPLC analysis of G. indica extract showed the highest content at pH 1 and 50
      degrees C. Using two different mobile phases, the limits of detection (LOD) for
      cyanidin-3-O-sambubioside and cyanidin-3-O-glucoside were 0.036 and 0.059, and
      0.022 and 0.033 mg kg-1, respectively. Furthermore, the inter-day precision (<
      3.2%) confirmed that the applied analytical method fulfils the required criteria
      of Association of Official Analytical Chemists (AOAC). From this study, it was
      found that the HPLC method used for the detection of adulteration in G. cambogia
      products is rapid and accurate.

PMID- 27702397
TI  - Isolation, Characterization, and In Vitro Culturing of Spermatogonial Stem Cells
      in Japanese Quail (Coturnix japonica).
AB  - We reported previously testis-mediated germline chimera production and
      characterization of germline stem cell-like cells from chicken testes. The
      present study aimed to establish an in vitro system for culture of quail
      spermatogonial stem cells (SSCs) for practical applications in germline
      preservation and transgenesis. Testicular cells (TCs) from juvenile (4 weeks old)
      or adult (8 weeks old) quail testis were isolated using sequential enzymatic
      digestion. The percentages of viability of isolated TCs were 91.00% +/- 2.12% and
      88.00% +/- 1.87% in juvenile and adult testes, respectively, and
      immunohistochemical evaluation indicated the expression of integrin alpha-6
      (ITGA6), GDNF family receptor alpha-1 (GFRA1), and Deleted in azoospermia-like
      (DAZL) in specific TCs. SSCs were purified by differential plating of TCs and
      then subjected to quantitative reverse transcription-polymerase chain reaction,
      which showed differential expression of SSC-specific, and germness and stemness
      related genes. Coculture of quail SSCs with mouse embryonic fibroblasts and
      Sertoli cells as a feeder layer resulted in the generation of stable SSC colonies
      and short-term cultivation, and the expression of SSC and germ cell markers was
      maintained during several passages of culture. Collectively, these results
      demonstrate the efficient isolation and characterization of quail SSCs and the
      suitability of Sertoli cells as a feeder layer for in vitro culture of quail
      SSCs. Quail SSCs will facilitate the production of germline chimeras and
      transgenesis.

PMID- 27702396
TI  - Calvarial Defect Healing Induced by Small Molecule Smoothened Agonist.
AB  - Hedgehog (Hh) signaling positively regulates both endochondral and
      intramembranous ossification. Use of small molecules for tissue engineering
      applications poses several advantages. In this study, we examined whether use of
      an acellular scaffold treated with the small molecule Smoothened agonist (SAG)
      could aid in critical-size mouse calvarial defect repair. First, we verified the
      pro-osteogenic effect of SAG in vitro, using primary neonatal mouse calvarial
      cells (NMCCs). Next, a 4 mm nonhealing defect was created in the mid-parietal
      bone of 10-week-old CD-1 mice. The scaffold consisted of a custom-fabricated
      poly(lactic-co-glycolic acid) disc with hydroxyapatite coating (measuring 4 mm
      diameter * 0.5 mm thickness). Treatment groups included dimethylsulfoxide control
      (n = 6), 0.5 mM SAG (n = 7) or 1.0 mM SAG (n = 7). Evaluation was performed at 4
      and 8 weeks postoperative, by a combination of high-resolution microcomputed
      tomography, histology (H & E, Masson's Trichrome), histomorphometry, and
      immunohistochemistry (BSP, OCN, VEGF). In vivo results showed that SAG treatment
      induced a significant and dose-dependent increase in calvarial bone healing by
      all radiographic parameters. Histomorphometric analysis showed an increase in all
      parameters of bone formation with SAG treatment, but also an increase in blood
      vessel number and density. In summary, SAG is a pro-osteogenic, provasculogenic
      stimulus when applied locally in a bone defect environment.

PMID- 27702398
TI  - Mesenchymal Stem Cells and Pericytes: To What Extent Are They Related?
AB  - Mesenchymal stem cells (MSCs) were initially identified as progenitors of
      skeletal tissues within mammalian bone marrow and cells with similar properties
      were also obtained from other tissues such as adipose and dental pulp. Although
      MSCs have been extensively investigated, their native behavior and in vivo
      identity remain poorly defined. Uncovering the in vivo identity of MSCs has been
      challenging due to the lack of exclusive cell markers, cellular alterations
      caused by culture methods, and extensive focus on in vitro properties for
      characterization. Although MSC site of origin influences their functional
      properties, these mesenchymal progenitors can be found in the perivascular space
      in virtually all organs from where they were obtained. However, the precise
      identity of MSCs within the vascular wall is highly controversial. The recurrent
      concept that MSCs correspond to pericytes in vivo has been supported mainly by
      their perivascular localization and expression of some molecular markers.
      However, this view has been a subject of controversy, in part, due to the
      application of loose criteria to define pericytes and due to the lack of a marker
      able to unequivocally identify these cells. Furthermore, recent evidences
      indicate that subpopulations of MSCs can be found at extravascular sites such as
      the endosteum. In this opinion review, we bring together the advances and
      pitfalls on the search for the in vivo identity of MSCs and highlight the recent
      evidences that suggest that perivascular MSCs are adventitial cells, acting as
      precursors of pericytes and other stromal cells during tissue homeostasis.

PMID- 27702399
TI  - Negative work perception not changed in a short work-anxiety-coping group therapy
      intervention.
AB  - BACKGROUND: Work anxiety is often associated with long-term sick leave and
      requires early intervention. Work anxieties are associated with negative work
      perception. Therefore, one aim in early intervention is a cognitive reframing of
      dysfunctional perceptions of workplace characteristics. METHODS: A
      psychotherapeutic specialist conducted two group programs of four sessions each.
      One hundred twenty-three rehabilitation in-patients with work anxieties were
      randomly assigned either to a work anxiety-coping group or to a recreational
      group. The Short Questionnaire for Work Analysis (KFZA) was administered before
      and after the group treatment to measure perceptions of working conditions.
      RESULTS: Participants from the work anxiety-coping group did not see their work
      in a significantly more positive light at the end of the intervention compared to
      participants from the recreational group. CONCLUSIONS: A short work anxiety
      coping group did not initiate a consistent positive re-appraisal of work.
      Employers and occupational physicians should not expect positive changes of work
      perception when an employee returns from short medical rehabilitation including
      work-directed treatment. Additional support from the workplace must be
      considered, e.g. employer-physician-employee conversation preceding return to
      work, or (temporary) work adjustment.

PMID- 27702400
TI  - Association of aplastic anemia and FoxP3 gene polymorphisms in Koreans.
AB  - OBJECTIVES: Aplastic anemia (AA) is characterized by pancytopenia and bone marrow
      failure, and most acquired AA is an immune-mediated disorder. Regulatory T cells
      (Tregs) suppressing autoreactive T cells were decreased in AA patients. FoxP3 is
      a major regulator for the development and function of Tregs. Polymorphism in
      FoxP3 was shown to be associated with various autoimmune diseases, however, has
      not yet been studied in AA. In this study, we examined the association between
      FoxP3 polymorphisms and AA in Korean patients. METHODS: The study population
      consisted of 94 patients diagnosed by bone marrow examination in Seoul National
      University Hospital (SNUH) during 1997-2012 and 195 healthy controls. FoxP3
      polymorphisms (rs5902434 del/ATT, rs3761548 C/A, rs3761549 C/T, rs2232365 A/G)
      were analyzed by PCR-sequencing method. We analyzed differences of genotype and
      allele frequencies between patients and controls. We also compared differences of
      genotype and allele frequencies between responder and non-responder in patients
      treated with immunosuppressive therapy (IST). For the statistical analysis, the
      chi-square test and Fisher's exact test were used and P < 0.05 was regarded as
      statistically significant. RESULTS: There was no significant difference in the
      genotype frequencies of FoxP3 polymorphisms between patients and controls. With
      regards to the allele frequencies, rs3761548 C allele was significantly higher in
      AA patients than in controls (87.4% vs. 79.7%, P = 0.047). In patients treated
      with IST, rs3761549 C allele was significantly higher in non-responder patients
      than in responders (89.6% vs. 66.7%, P = 0.036) and female rs3761549 C/C genotype
      carriers were associated with greater risk for non-response to IST (84.2% vs.
      16.7%, P = 0.006). CONCLUSION: Polymorphisms in rs3761548 and rs3761549 of FoxP3
      in our population were associated with disease susceptibility and response for
      IST, respectively. This study suggests an association between FoxP3 polymorphisms
      and AA in Korean patients and will be useful in further understanding the genetic
      basis of disease susceptibility and response to IST in AA patients.

PMID- 27702401
TI  - Evaluation of the orthodontic component of the hypodontia care pathway.
AB  - INTRODUCTION: This study evaluated patients' experiences of the Hypodontia Care
      Pathway at a large teaching hospital at key stages: specifically patient
      expectations/experience following the diagnosis of hypodontia and then patient
      satisfaction with the orthodontic care received and the outcome at the end of
      active orthodontic treatment. METHODOLOGY: In-depth, semi-structured interviews
      were conducted with 20 hypodontia patients following completion of orthodontic
      treatment but prior to any planned prosthodontic treatment commencing. Interviews
      were analysed qualitatively, using a framework approach. RESULTS: The framework
      analysis identified four main themes: perceptions of treatment, impact of the
      original malocclusion and the treatment process, the care team and communication.
      The themes were then further divided into subthemes. DISCUSSION: There was a
      large amount of positive feedback and the importance of the patient-clinician
      relationship was evident throughout. Where issues of concern were identified,
      these related mainly to communication and areas were identified where change
      could take place in the future. CONCLUSIONS: Positive feedback was received and
      the importance of patient-clinician rapport was highlighted in all interviews.
      The main areas that could be enhanced related to the importance of ensuring
      optimum communication, particularly with a cohort of patients who are often
      undergoing complex multidisciplinary treatment. Recommendations for the service
      have been made.

PMID- 27702402
TI  - Development of Antithrombotic Aptamers: From Recognizing Elements to Drugs.
AB  - Blood hemostasis is attained with two sophisticated interconnected network
      systems, a coagulation cascade and a platelet activation system. Multiple
      inhibitors were developed to various components of both systems to prevent
      thrombosis-related morbid events that are of extremely high frequency in the
      human population. Antithrombotic inhibitors possess both positive and negative
      aspects. One of the essential modern requirements is a controllable mode of
      action for both anticoagulants and antiplatelets that could be achieved due to
      the high affinity and specificity of the inhibitor, as well as a possibility to
      apply an antidote, which quickly annihilates activity of the inhibitor and
      restores the proper hemostasis. Aptamers are DNA or RNA oligonucleotides with
      particular tertiary structure, such as DNA guanine quadruplex. Besides antibodies
      and other peptides/proteins, aptamers are one more example of the molecular
      recognizing elements that specifically bind to the target. Therefore, aptamers
      could be developed into a promising novel class of the drugs with high affinity,
      specificity, innate low toxicity, and rational antidote. Several aptamers with
      prospective antithrombotic activity have been reviewed; some of them are in
      preclinical and clinical trials.

PMID- 27702403
TI  - [Five years of Fiom KID-DNA Databank: experiences in matching sperm donors and
      donor-conceived offspring].
AB  - Before the introduction of the Dutch Human Fertilisation (Donor Information) Act
      (in Dutch: Wet Donorgegevens Kunstmatige Bevruchting) in 2004, approximately
      40,000 donor-conceived offspring were born in the Netherlands. The majority is
      conceived by means of artificial insemination with anonymous donor sperm (in
      Dutch: kunstmatige inseminatie met anoniem donorzaad - KID). This means that they
      have little or no access to information about their genetic origins. Through the
      Fiom KID-DNA Databank, established in 2010 in association with the Canisius
      Wilhelmina Hospital, it is possible for these donor-conceived offspring and
      donors to search for one another. DNA profiles are used to match donor-conceived
      offspring, donors and half-siblings. It is expected that the number of donor
      related searches will increase. The experiences with matching and counselling of
      donor-conceived offspring and donors presented in this paper will help donor
      conceived offspring and donors who start a search in the future. Moreover, they
      provide guidance for forming a meaningful relationship between those involved.

PMID- 27702404
TI  - [Fibrous dysplasia: a heterogeneous disease].
AB  - Fibrous dysplasia is a rare genetic bone disorder with a wide variation in
      clinical expression, ranging from asymptomatic patients to severely affected
      patients with extensive bone disease, pain, repetitive fractures and deformities
      and serious endocrinological symptoms (McCune-Albright syndrome). Here, we report
      on three different cases of fibrous dysplasia. First, a 46-year-old woman with a
      small solitary lesion in the proximal femur. Second, a 25-year-old man with
      polyostotic disease of the left leg who received both surgical and medical
      treatment. Third, a 7-year-old girl with McCune-Albright syndrome who was
      diagnosed with precocious puberty as a baby and who had extensive disease
      throughout the skeleton, including multiple lesions in the craniofacial region.
      The aetiology, clinical expression, diagnostic work-up and therapeutic options
      for fibrous dysplasia are discussed in a short resume of the disease.

PMID- 27702405
TI  - [Can apps encourage a healthier and more active lifestyle?]
AB  - OBJECTIVE: To present an overview of the literature on the effect of smartphone
      apps and activity trackers on a healthy lifestyle. DESIGN: Systematic review.
      METHOD: PubMed, the Cochrane Library, Embase and CINAHL were searched for
      relevant articles. Inclusion criteria were: (a) the intervention was a mobile app
      or activity tracker; (b) that stimulated activity and healthy diet; (c) in adults
      with an unhealthy lifestyle but so far without medical disorders; (d) aimed at
      preventative healthcare, improvement in health or healthy behaviour; and (e)
      measured the effect of physical activity, diet and weight. RESULTS: We included
      17 studies, of which 13 involved apps and 4 involved activity trackers. The
      effect of the apps on physical activity in overweight or obese people was
      positive in 6 studies, while no effect was found in 3 studies. There was a
      positive effect on diet; this was significant in 3 studies and non-significant in
      2 studies. The effect on weight was positive in 6 studies, while no effect was
      found in 5 studies. Evidential value of the studies involving apps was poor to
      moderate. Activity trackers seemed to have the power to increase physical
      activity, but quality of these studies was poor. The effects on weight were
      contradictory and the effects on diet were not investigated. CONCLUSION: Apps
      have a global positive effect on physical activity. The effect of apps on diet
      and weight is unclear, but the trend is that they improve eating patterns.
      Activity trackers can increase physical activity. Larger scale research with more
      balanced control groups and longer follow-up is, however, necessary before we can
      recommend the use of apps and activity trackers.

PMID- 27702407
TI  - [Diagnostics and treatment of lower extremity peripheral arterial disease;
      guideline and registry].
AB  - - Revision of the 2005 guideline 'Diagnostics and treatment of lower extremity
      peripheral arterial disease' and the development of an audit have instigated a
      degree of efficiency and transparency for the treatment of patients with
      peripheral arterial disease (PAD). - The key recommendations are that first-line
      treatment of patients, who - preferably by means of a consultation in a vascular
      laboratory - are diagnosed with intermittent claudication, is supervised exercise
      therapy and secondary prevention. Referral for second-line treatment only needs
      to occur when invasive therapy is considered, for example when there is
      insufficient improvement in symptoms or in patients who have or are developing
      critical ischemia. - In case of endovascular treatments it is not necessary to
      insert stents routinely; this can be reserved for cases where the angiographic
      result of the angioplasty is insufficient. - All patients with PAD are registered
      on the DAPA register ('Dutch audit for peripheral arterial disease'), which has
      two unique characteristics: patient reported outcome measures (PROMs) are
      recorded and a case mix correction is incorporated for the PROMs and amputation
      free survival through linkage with the health insurance database.

PMID- 27702406
TI  - [Is a salt-restricted diet now up for discussion?]
AB  - A recent meta-analysis published in The Lancet related sodium excretion to
      mortality in both hypertensive and normotensive subjects. High salt excretion,
      measured in a spot urine test, was related to increased mortality in hypertensive
      subjects only, whereas low sodium excretion was related to increased mortality in
      both hypertensive and normotensive subjects. Here we discuss practical
      consequences of this analysis. The data underline the importance of salt
      restriction in hypertension; the analysis also shows that there is a lower limit
      to salt restriction. Since salt intake cannot be assessed adequately from the
      sodium content of a single urine sample, 24-hour urine collection is advised in
      subjects on a salt-restricted diet. A 24-hour urine collection allows checking
      for unnecessarily strict salt restriction or, as will more often be the case,
      shows the patient that adequate salt restriction has not yet been attained.

PMID- 27702408
TI  - [Effectiveness of lifestyle apps not yet proven].
AB  - In a systematic review in the Dutch Journal of Medicine (NTvG), Dallinga et al.
      look for an answer to the societally relevant question of whether mobile apps are
      proven to lead to a more active and healthy lifestyle. Decision makers in
      healthcare have high expectations of eHealth, a field where scientific evidence
      sometimes seems overruled merely by the opinions of self-declared 'futurists'.
      Commonly, eHealth is propelled forward as the solution to the lack of manpower in
      healthcare, given the expected rise of chronic disease. However, an earlier
      analysis of 108 systematic reviews on the impact of eHealth technologies shows
      that a plethora of claims are not supported by sound evidence. It is therefore
      worthwhile to assess the current evidence for the effectiveness of health apps on
      exercise and healthy nutrition.

PMID- 27702410
TI  - Decontamination in the Electron Probe Microanalysis with a Peltier-Cooled Cold
      Finger.
AB  - A prototype Peltier thermoelectric cooling unit has been constructed to cool a
      cold finger on an electron microprobe. The Peltier unit was tested at 15 and 96
      W, achieving cold finger temperatures of -10 and -27 degrees C, respectively. The
      Peltier unit did not adversely affect the analytical stability of the instrument.
      Heat conduction between the Peltier unit mounted outside the vacuum and the cold
      finger was found to be very efficient. Under Peltier cooling, the vacuum
      improvement associated with water vapor deposition was not achieved; this has the
      advantage of avoiding severe degradation of the vacuum observed when warming up a
      cold finger from liquid nitrogen (LN2) temperatures. Carbon contamination rates
      were reduced as cooling commenced; by -27 degrees C contamination rates were
      found to be comparable with LN2-cooled devices. Peltier cooling, therefore,
      provides a viable alternative to LN2-cooled cold fingers, with few of their
      associated disadvantages.

PMID- 27702409
TI  - The relationship between micronutrient status and sleep patterns: a systematic
      review.
AB  - OBJECTIVE: To review articles on the relationship of dietary and circulating
      micronutrients with sleep patterns, and to identify issues surrounding
      implications for future research and public health practice. DESIGN: A systematic
      review was conducted. PubMed, Embase and Scopus were searched through January
      2016. SETTING: Both experimental and observational studies were included.
      However, studies that focused on secondary sleep impairment due to comorbidities
      were excluded. SUBJECTS: Individuals in different age groups, from infants to
      older adults. RESULTS: A total of twenty-six articles were selected. In the
      articles reviewed, researchers generally supported a potential role of
      micronutrients, particularly Fe and Mg, in the development of sleep stages among
      infants and in reversing age-related alterations in sleep architecture in older
      adults. Micronutrient status has also been linked to sleep duration, with sleep
      duration positively associated with Fe, Zn and Mg levels, and negatively
      associated with Cu, K and vitamin B12 levels. The mechanisms underlying these
      relationships include the impact of micronutrients on excitatory/inhibitory
      neurotransmitters and the expression of circadian genes. CONCLUSIONS: Although
      the number of studies on the relationship between micronutrient status and sleep
      remains low, evidence has emerged that suggests a link between
      dietary/circulating micronutrients and sleep. Future research is needed to
      investigate the dose-dependent as well as the longitudinal relationships between
      micronutrient levels and human sleep across populations, test the interactions
      among micronutrients on sleep outcomes, and ultimately examine the clinical
      relevance of micronutrients on sleep health.

PMID- 27702411
TI  - Effect of agomelatine treatment on C-reactive protein levels in patients with
      major depressive disorder: an exploratory study in "real-world," everyday
      clinical practice.
AB  - OBJECTIVE: Agomelatine is a newer antidepressant but, to date, no studies have
      been carried out investigating its effects on C-reactive protein (CRP) levels in
      major depressive disorder (MDD) before and after treatment. The present study
      aimed (i) to investigate the effects of agomelatine treatment on CRP levels in a
      sample of patients with MDD and (ii) to investigate if CRP variations were
      correlated with clinical improvement in such patients. METHODS: 30 adult
      outpatients (12 males, 18 females) with a Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of MDD were
      recruited in "real-world," everyday clinical practice and treated with a flexible
      dose of agomelatine for 12 weeks. The Hamilton Rating Scale for Depression (HAM
      D) and the Snaith-Hamilton Pleasure Scale (SHAPS) were used to evaluate
      depressive symptoms and anhedonia, respectively. Moreover, serum CRP was measured
      at baseline and after 12 weeks of treatment. RESULTS: Agomelatine was effective
      in the treatment of MDD, with a significant reduction in HAM-D and SHAPS scores
      from baseline to endpoint. CRP levels were reduced in the whole sample, with
      remitters showing a significant difference in CRP levels after 12 weeks of
      agomelatine. A multivariate stepwise linear regression analysis showed that
      higher CRP level variation was associated with higher baseline HAM-D scores,
      controlling for age, gender, smoking, BMI, and agomelatine dose. CONCLUSIONS:
      Agomelatine's antidepressant properties were associated with a reduction in
      circulating CRP levels in MDD patients who achieved remission after 12 weeks of
      treatment. Moreover, more prominent CRP level variation was associated with more
      severe depressive symptoms at baseline.

PMID- 27702412
TI  - Where do food desert residents buy most of their junk food? Supermarkets.
AB  - OBJECTIVE: To examine where residents in an area with limited access to healthy
      foods (an urban food desert) purchased healthier and less healthy foods. DESIGN:
      Food shopping receipts were collected over a one-week period in 2013. These were
      analysed to describe where residents shopped for food and what types of food they
      bought. SETTING: Two low-income, predominantly African-American neighbourhoods
      with limited access to healthy foods in Pittsburgh, PA, USA. SUBJECTS: Two
      hundred and ninety-three households in which the primary food shoppers were
      predominantly female (77.8 %) and non-Hispanic black (91.1 %) adults. RESULTS:
      Full-service supermarkets were by far the most common food retail outlet from
      which food receipts were returned and accounted for a much larger proportion
      (57.4 %) of food and beverage expenditures, both healthy and unhealthy, than
      other food retail outlets. Although patronized less frequently, convenience
      stores were notable purveyors of unhealthy foods. CONCLUSIONS: Findings highlight
      the need to implement policies that can help to decrease unhealthy food purchases
      in full-service supermarkets and convenience stores and increase healthy food
      purchases in convenience stores.

PMID- 27702413
TI  - Urinary sodium-to-potassium ratio: it may be SMART, but is it easy?

PMID- 27702414
TI  - Validity of LIDAS (LIfetime Depression Assessment Self-report): a self-report
      online assessment of lifetime major depressive disorder.
AB  - BACKGROUND: There is a paucity of valid, brief instruments for the assessment of
      lifetime major depressive disorder (MDD) that can be used in, for example, large
      scale genomics, imaging or biomarker studies on depression. We developed the
      LIfetime Depression Assessment Self-report (LIDAS), which assesses lifetime MDD
      diagnosis according to DSM criteria, and is largely based on the widely used
      Composite International Diagnostic Interview (CIDI). Here, we tested the
      feasibility and determined the sensitivity and specificity for measuring lifetime
      MDD with this new questionnaire, with a regular CIDI as reference. METHOD:
      Sensitivity and specificity analyses of the online lifetime MDD questionnaire
      were performed in adults with (n = 177) and without (n = 87) lifetime MDD
      according to regular index CIDIs, selected from the Netherlands Study of
      Depression and Anxiety (NESDA) and Netherlands Twin Register (NTR). Feasibility
      was tested in an additional non-selective, population-based sample of NTR
      participants (n = 245). RESULTS: Of the 753 invited persons, 509 (68%) completed
      the LIDAS, of which 419 (82%) did this online. User-friendliness of the
      instrument was rated high. Median completion time was 6.2 min. Sensitivity and
      specificity for lifetime MDD were 85% [95% confidence interval (CI) 80-91%] and
      80% (95% CI 72-89%), respectively. This LIDAS instrument gave a lifetime MDD
      prevalence of 20.8% in the population-based sample. CONCLUSIONS: Measuring
      lifetime MDD with an online instrument was feasible. Sensitivity and specificity
      were adequate. The instrument gave a prevalence of lifetime MDD in line with
      reported population prevalences. LIDAS is a promising tool for rapid
      determination of lifetime MDD status in large samples, such as needed for
      genomics studies.

PMID- 27702415
TI  - Shared Genetic Factors in the Co-Occurrence of Depression and Fatigue.
AB  - Depression and fatigue have previously been suggested to share an underlying
      genetic contribution. The present study aims to investigate and characterize the
      familiality and genetic relationship between depression and fatigue. The
      familiality of depression and fatigue was assessed by calculating relative risks,
      measured by the prevalence ratio, within 643 monozygotic (MZ) and 577 dizygotic
      (DZ) twin pairs. Bivariate twin modeling was utilized to assess the magnitude of
      shared heritability between depression and fatigue. Finally, the relationship
      between depression and fatigue was investigated using the co-twin control method,
      to determine whether the association is explained by causal or non-causal models.
      We observed an increased risk of fatigue in co-twins of probands with depression
      and increased risk of depression in co-twins of probands with fatigue. Higher
      risks were observed in MZ compared to DZ twin pairs, and bivariate heritability
      analyses indicated significant genetic components for depression and fatigue,
      with heritability estimates of 48% and 41%, respectively. Importantly, a
      significant additive genetic correlation of 0.71 [95% CI = 0.51-0.92) and
      bivariate heritability of 21% [95% CI = 10-35%] was observed between depression
      and fatigue. Furthermore, results from the co-twin control method indicate a non
      causal genetic relationship that likely explains the association between
      depression and fatigue. Notably, the contribution of shared genetic factors
      remained significant, independent of the overlapping symptoms, indicating that
      the relationship between co-occurring depression and fatigue is primarily due to
      shared genetic factors rather than overlapping symptomatology.

PMID- 27702416
TI  - Coil occlusion of aberrant arteries to pulmonary sequestration in a case with
      pulmonary atresia with intact ventricular septum: successful treatment of
      repetitive myocardial ischaemic attacks.
AB  - In this study, we describe an infant case of pulmonary atresia with intact
      ventricular septum associated with ventriculo-coronary arterial communication for
      which a modified Blalock-Taussig shunt operation was performed. He experienced
      repeated myocardial ischaemic attacks. Further examination revealed pulmonary
      sequestration in the right lower lobe. He therefore underwent a bidirectional
      Glenn operation and coil occlusion of the feeding arteries. His myocardial
      ischaemic attacks subsequently improved.

PMID- 27702417
TI  - Differences in expenditure and amounts of fresh foods, fruits and vegetables, and
      fish purchased in urban and rural Scotland.
AB  - OBJECTIVE: To quantitatively analyse expenditure on all fresh foods, fruits and
      vegetables (F&V) and fish across urban and rural households in Scotland. Fresh
      foods were chosen since, in general, they are perceived to contribute more to
      health than processed foods. DESIGN: Descriptive analysis of purchase data of all
      foods brought into the home during 2012 from the Kantar Worldpanel database.
      Purchase data were restricted to fresh, unprocessed and raw foods or 'fresh to
      frozen' foods where freezing was part of harvesting. Total household purchases
      were adjusted for household size and composition. SETTING: Scotland. SUBJECTS:
      Households (n 2576). RESULTS: Rural households reported the highest expenditure
      per person on fresh foods and F&V, but also bought the most (kilograms) of these
      items. There were linear trends of average prices paid with urban-rural location
      (P<0.001), with average prices paid by large urban and remote rural households
      being L2.14/kg and L2.04/kg for fresh foods, L1.64/kg and L1.60/kg for F&V and
      L10.07/kg and L10.20/kg for fish, respectively, although differences were
      quantitatively small. CONCLUSIONS: Contrary to previous studies, purchase data
      show that access to and average prices of fresh foods generally, and F&V and fish
      specifically, are broadly similar between urban and rural areas. Therefore, the
      higher expenditure on these foods in rural v. urban areas is probably due to
      factors other than pricing and availability.

PMID- 27702418
TI  - Density mediates grasshopper performance in response to temperature manipulation
      and spider predation in tallgrass prairie.
AB  - Species interactions are often context-dependent, where outcomes require an
      understanding of influences among multiple biotic and abiotic factors. However,
      it remains unclear how abiotic factors such as temperature combine with important
      biotic factors such as density-dependent food limitation and predation to
      influence species interactions. Using a native grassland - grasshopper - wolf
      spider model food chain in tallgrass prairie, we conducted a manipulative field
      experiment to examine how predator-prey interactions respond to manipulations of
      temperature, grasshopper density, and food chain length. We find that grasshopper
      performance responses to temperature and predator treatments were density
      dependent. At high densities, grasshopper survival decreased with increased
      temperature when no spiders were present. When spiders were present, grasshopper
      survival was reduced, and this effect was strongest in the cooled treatment. In
      contrast, grasshopper survival did not vary significantly with spider presence or
      among temperature treatments at low grasshopper densities. Our results indicate
      that context-dependent species interactions are common and highlight the
      importance of understanding how and when key biotic and abiotic factors combine
      to influence species interactions.

PMID- 27702419
TI  - Expression of the T85A mutant of zebrafish aquaporin 3b improves post-thaw
      survival of cryopreserved early mammalian embryos.
AB  - While vitrification has become the method of choice for preservation of human
      oocytes and embryos, cryopreservation of complex tissues and of large yolk
      containing cells, remains largely unsuccessful. One critical step in such
      instances is appropriate permeation while avoiding potentially toxic
      concentrations of cryoprotectants. Permeation of water and small non-charged
      solutes, such as those used as cryoprotectants, occurs largely through membrane
      channel proteins termed aquaporins (AQPs). Substitution of a Thr by an Ala
      residue in the pore-forming motif of the zebrafish (Dario rerio) Aqp3b paralog
      resulted in a mutant (DrAqp3b-T85A) that when expressed in Xenopus or porcine
      oocytes increased their permeability to ethylene glycol at pH 7.5 and 8.5. The
      main objective of this study was to test whether ectopic expression of DrAqp3b
      T85A also conferred higher resistance to cryoinjury. For this, DrAqp3b-T85A +
      eGFP (reporter) cRNA, or eGFP cRNA alone, was microinjected into in vivo
      fertilized 1-cell mouse zygotes. Following culture to the 2-cell stage,
      appropriate membrane expression of DrAqp3b-T85A was confirmed by
      immunofluorescence microscopy using a primary specific antibody directed against
      the C-terminus of DrAqp3b. Microinjected 2-cell embryos were then cryopreserved
      using a fast-freezing rate and low concentration (1.5 M) of ethylene glycol in
      order to highlight any benefits from DrAqp3b-T85A expression. Notably, post-thaw
      survival rates were higher (P<0.05) for T85A-eGFP-injected than for -uninjected
      or eGFP-injected embryos (73+/-7.3 vs. 28+/-7.3 or 14+/-6.7, respectively). We
      propose that ectopic expression of mutant AQPs may provide an avenue to improve
      cryopreservation results of large cells and tissues in which current
      vitrification protocols yield low survival.

PMID- 27702420
TI  - Clinical management of restless legs syndrome in end-stage renal disease
      patients.
AB  - Restless legs syndrome (RLS) is a common neurological movement disorder,
      characterized by restless and unpleasant sensations in the deep inside of legs.
      The symptoms of RLS are less noticeable during daytime, but more prevalent at
      night. Therefore, the disorder can induce low quality of life, insomnia, and
      impairment of daytime activity. RLS in end-stage renal disease (ESRD) patients is
      especially problematic due to premature discontinuation of dialysis and increased
      mortality. The prevalence of RLS among dialysis patients is much higher compared
      to the prevalence of the same disorder in patients with normal renal functions.
      Even though there are recommended treatment guidelines for the general population
      established by Medical Advisory Board of the RLS foundation, which include the
      use of dopamine agonists, levodopa, gabapentin, benzodiazepines, and opioids,
      limited information is available on the effects of these therapies in ESRD
      patients. Since the existing clinical data were extrapolated from small sample
      sizes in short-term clinical trials, further clinical studies are still needed to
      better assess the efficacy, safety, and tolerability of these medications in
      patients with ESRD.

PMID- 27702421
TI  - Non-farmed fish contribute to greater micronutrient intakes than farmed fish:
      results from an intra-household survey in rural Bangladesh.
AB  - OBJECTIVE: Fish is the most important animal-source food (ASF) in Bangladesh,
      produced from capture fisheries (non-farmed) and aquaculture (farmed) sub
      sectors. Large differences in micronutrient content of fish species from these
      sub-sectors exist. The importance of fish in diets of vulnerable groups compared
      with other ASF; contribution from non-farmed and farmed species to nutrient
      intakes; and differences in fish consumption among age, gender, wealth groups and
      geographic regions were analysed, using quantitative intra-household fish
      consumption data, focusing on the first 1000 d of life. DESIGN: Two-stage
      stratified sample. SETTING: Nationally representative of rural Bangladesh.
      SUBJECTS: Households (n 5503) and individuals (n 24 198). RESULTS: Fish
      consumption in poor households was almost half that in wealthiest households; and
      lower in females than males in all groups, except the wealthiest, and for those
      aged >=15 years (P<0.01). In infants of complementary feeding age, 56 % did not
      consume ASF on the survey day, despite 78 % of mothers knowing this was
      recommended. Non-farmed fish made a larger contribution to Fe, Zn, Ca, vitamin A
      and vitamin B12 intakes than farmed fish (P<0.0001). CONCLUSIONS: Policies and
      programmes aimed to increase fish consumption as a means to improve nutrition in
      rural Bangladesh should focus on women and young children, and on the poorest
      households. Aquaculture plays an important role in increasing availability and
      affordability of fish; however, non-farmed fish species are better placed to
      contribute to greater micronutrient intakes. This presents an opportunity for
      aquaculture to contribute to improved nutrition, utilising diverse production
      technologies and fish species, including small fish.

PMID- 27702423
TI  - SOCE proteins, STIM1 and Orai1, are localized to the cleavage furrow during
      cytokinesis of the first and second cell division cycles in zebrafish embryos.
AB  - In zebrafish embryos, distinct Ca2+ transients are localized to the early
      cleavage furrows during the first few cell division cycles. These transients are
      generated mainly by release via IP3Rs in the endoplasmic reticulum, and they are
      necessary for furrow positioning, propagation, deepening and apposition. We
      previously showed, via the use of inhibitors, that store-operated Ca2+ entry
      (SOCE) also appears to be essential for maintaining the IP3R-mediated elevated
      levels of [Ca2+]i for the extended periods required for the completion of
      successful furrow deepening and daughter cell apposition in these large embryonic
      cells. Here, newly fertilized, dechorionated embryos were fixed at various times
      during the first and second cell division cycles and immunolabelled with
      antibodies to STIM1 and/or Orai1 (key components of SOCE). We show that both of
      these proteins have a dynamic pattern of localization during cytokinesis of the
      first two cell division cycles. These new data help to support our previous
      inhibitor results, and provide additional evidence that SOCE contributes to the
      maintenance of the sustained elevated Ca2+ that is required for the successful
      completion of cytokinesis in the large cells of embryonic zebrafish.

PMID- 27702422
TI  - Parental supply of alcohol and alcohol consumption in adolescence: prospective
      cohort study.
AB  - BACKGROUND: Parents are a major supplier of alcohol to adolescents, yet there is
      limited research examining the impact of this on adolescent alcohol use. This
      study investigates associations between parental supply of alcohol, supply from
      other sources, and adolescent drinking, adjusting for child, parent, family and
      peer variables. METHOD: A cohort of 1927 adolescents was surveyed annually from
      2010 to 2014. Measures include: consumption of whole drinks; binge drinking (>4
      standard drinks on any occasion); parental supply of alcohol; supply from other
      sources; child, parent, family and peer covariates. RESULTS: After adjustment,
      adolescents supplied alcohol by parents had higher odds of drinking whole
      beverages [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.33-2.45] than
      those not supplied by parents. However, parental supply was not associated with
      bingeing, and those supplied alcohol by parents typically consumed fewer drinks
      per occasion (incidence rate ratio 0.86, 95% CI 0.77-0.96) than adolescents
      supplied only from other sources. Adolescents obtaining alcohol from non-parental
      sources had increased odds of drinking whole beverages (OR 2.53, 95% CI 1.86
      3.45) and bingeing (OR 3.51, 95% CI 2.53-4.87). CONCLUSIONS: Parental supply of
      alcohol to adolescents was associated with increased risk of drinking, but not
      bingeing. These parentally-supplied children also consumed fewer drinks on a
      typical drinking occasion. Adolescents supplied alcohol from non-parental sources
      had greater odds of drinking and bingeing. Further follow-up is necessary to
      determine whether these patterns continue, and to examine alcohol-related harm
      trajectories. Parents should be advised that supply of alcohol may increase
      children's drinking.

PMID- 27702424
TI  - Duration of periconceptional folic acid supplementation in women booking for
      antenatal care.
AB  - OBJECTIVE: To provide accurate estimates of the commencement time, duration and
      dosage of folic acid (FA) supplementation taken by Irish women in the
      periconceptional period. The study also aimed to establish the factors associated
      with optimal FA supplementation practices. DESIGN: Cross-sectional observational
      study. Women's clinical and sociodemographic details were computerised. Maternal
      weight and height were measured before calculating BMI. Detailed FA
      supplementation questionnaires were completed under the supervision of a trained
      researcher. SETTING: A large university maternity hospital, Republic of Ireland,
      January 2014-April 2016. SUBJECTS: Women (n 856) recruited at their convenience
      in the first trimester. RESULTS: While almost all of the women (97 %) were taking
      FA at enrolment, only one in four women took FA for at least 12 weeks
      preconceptionally (n 208). Among the 44 % of women who were supplementing with FA
      preconceptionally, 44 % (162/370) reported taking FA for less than the 12 weeks
      required to achieve optimal red-blood-cell folate levels for prevention of neural
      tube defects. On multivariate analysis, only planned pregnancy and nulliparity
      were associated with taking FA for at least 12 weeks preconceptionally. Among
      women who only took FA postconceptionally, almost two-thirds commenced it after
      day 28 of their pregnancy when the neural tube had already closed. CONCLUSIONS:
      As the timing of FA was suboptimal both before and after conception, we recommend
      that current national FA guidelines need to be reviewed.

PMID- 27702425
TI  - Nutrition education linked to agricultural interventions improved child dietary
      diversity in rural Cambodia.
AB  - Poor infant and young child feeding (IYCF) practices are major determinants of
      chronic malnutrition. The main objective of this study was to assess the impact
      of a nutrition education (NE) programme aimed at promoting improved IYCF
      behaviours in combination with an agriculture intervention on children's dietary
      diversity and nutritional status. From 2012 to 2014, a cluster randomised trial
      was rolled out in Cambodia in the context of an agriculture and nutrition project
      of the FAO of the UN. The cross-sectional baseline study was carried out in
      sixteen pre-selected communes in 2012. Restricted randomisation allotted the
      communes to either intervention (NE and agriculture intervention) or comparison
      arms (agriculture intervention only). The impact survey was conducted as a census
      in all FAO project villages in 2014. Caregivers of children aged 0-23 months were
      interviewed using standardised questions on socio-economic status and dietary
      diversity (24-h recall). Anthropometric measurements were taken. A difference-in
      differences model was applied. The sample comprised 743 households with children
      >=6 months of age at baseline and 921 at impact. After 1 year of NE, 69 % of the
      intervention households reported to have participated in the NE. Estimated mean
      child dietary diversity was significantly different at impact between comparison
      and intervention (3.6 and 3.9, respectively). In particular, the consumption of
      pro-vitamin A-rich foods and other fruits and vegetables increased. No treatment
      effects on height-for-age Z-scores could be shown. NE led to improvements in
      children's diets. For effects on growth, it is assumed that longer NE activities
      are required to achieve sustainable behaviour change of age-appropriate infant
      feeding.

PMID- 27702426
TI  - Burkholderia pseudomallei resistance to antibiotics in biofilm-induced conditions
      is related to efflux pumps.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, has been found to
      increase its resistance to antibiotics when growing as a biofilm. The resistance
      is related to several mechanisms. One of the possible mechanisms is the efflux
      pump. Using bioinformatics analysis, it was found that BPSL1661, BPSL1664 and
      BPSL1665 were orthologous genes of the efflux transporter encoding genes for
      biofilm-related antibiotic resistance, PA1874-PA1877 genes in Pseudomonas
      aeruginosa strain PAO1. Expression of selected encoding genes for the efflux
      transporter system during biofilm formation were investigated. Real-time reverse
      transcriptase PCR expression of amrB, cytoplasmic membrane protein of AmrAB-OprA
      efflux transporter encoding gene, was slightly increased, while BPSL1665 was
      significantly increased during growth of bacteria in biofilm formation. Minimum
      biofilm inhibition concentration and minimum biofilm eradication concentration
      (MBEC) of ceftazidime (CTZ), doxycycline (DOX) and imipenem were found to be 2-
      to 1024-times increased when compared to their MICs for of planktonic cells.
      Inhibition of the efflux transporter by adding phenylalanine arginine beta
      napthylamide (PAbetaN), a universal efflux inhibitor, decreased 2 to 16 times as
      much as MBEC in B. pseudomallei biofilms with CTZ and DOX. When the intracellular
      accumulation of antibiotics was tested to reveal the pump inhibition, only the
      concentrations of CTZ and DOX increased in PAbetaN treated biofilm. Taken
      together, these results indicated that BPSL1665, a putative precursor of the
      efflux pump gene, might be related to the adaptation of B. pseudomallei in
      biofilm conditions. Inhibition of efflux pumps may lead to a decrease of
      resistance to CTZ and DOX in biofilm cells.

PMID- 27702427
TI  - Presence of Cx43 in extracellular vesicles reduces the cardiotoxicity of the anti
      tumour therapeutic approach with doxorubicin.
AB  - Extracellular vesicles (EVs) are major conveyors of biological information,
      mediating local and systemic cell-to-cell communication under physiological and
      pathological conditions. These endogenous vesicles have been recognized as
      prominent drug delivery vehicles of several therapeutic cargoes, including
      doxorubicin (dox), presenting major advantages over the classical approaches.
      Although dox is one of the most effective anti-tumour agents in the clinical
      practice, its use is very often hindered by its consequent dramatic
      cardiotoxicity. Despite significant advances witnessed in the past few years,
      more comprehensive studies, supporting the therapeutic efficacy of EVs, with
      decreased side effects, are still scarce. The main objective of this study was to
      evaluate the role of the gap junction protein connexin43 (Cx43) in mediating the
      release of EV content into tumour cells. Moreover, we investigated whether Cx43
      improves the efficiency of dox-based anti-tumour treatment, with a concomitant
      decrease of cardiotoxicity. In the present report, we demonstrate that the
      presence of Cx43 in EVs increases the release of luciferin from EVs into tumour
      cells in vitro and in vivo. In addition, using cell-based approaches and a
      subcutaneous mouse tumour model, we show that the anti-tumour effect of dox
      incorporated into EVs is similar to the administration of the free drug,
      regardless the presence of Cx43. Strikingly, we demonstrate that the presence of
      Cx43 in dox-loaded EVs reduces the cardiotoxicity of the drug. Altogether, these
      results bring new insights into the concrete potential of EVs as therapeutic
      vehicles and open new avenues toward the development of strategies that help to
      reduce unwanted side effects.

PMID- 27702428
TI  - Food sources of energy and nutrients in Finnish girls and boys 6-8 years of age -
      the PANIC study.
AB  - BACKGROUND: Data on food sources of nutrients are needed to improve strategies to
      enhance nutrient intake among girls and boys in Western countries. OBJECTIVE: To
      identify major food sources of energy, energy nutrients, dietary fibre, and
      micronutrients, and to study gender differences in these food sources among
      children. DESIGN: We assessed food consumption and nutrient intake using 4-day
      food records in a population sample of Finnish girls (n=213) and boys (n=217)
      aged 6-8 years from the Physical Activity and Nutrition in Children Study. We
      calculated the percentual contribution of 55 food groups for energy and nutrient
      intake using the population proportion method. RESULTS: Low-fibre grain products,
      skimmed milk, and high-fibre bread provided almost 23% of total energy intake.
      Skimmed milk was the top source of protein (18% of total intake), vitamin D
      (32%), potassium (20%), calcium (39%), magnesium (17%), and zinc (16%). Vegetable
      oils (15%) and high-fat vegetable oil-based spreads (14%) were the top sources of
      polyunsaturated fat. High-fibre bread was the top source of fibre (27%) and iron
      (12%). Non-root vegetables were the top source of folate (14%) and vitamin C
      (22%). Sugar-sweetened beverages provided 21% of sucrose intake. Pork was a more
      important source of protein and sausage was a more important source of total fat
      and monounsaturated fat in boys than in girls. Vegetable oils provided a higher
      proportion of unsaturated fat and vitamin E among boys, whereas high-fat
      vegetable oil-based spreads provided a higher proportion of these nutrients among
      girls. CONCLUSION: Commonly recommended foods, such as skimmed milk, high-fibre
      grain products, vegetables, vegetable oil, and vegetable oil-based spreads, were
      important sources of several nutrients, whereas sugar-sweetened beverages
      provided the majority of sucrose intake among children. This knowledge can be
      used in improving health among children by dietary interventions, nutrition
      education, and health policy decision making.

PMID- 27702429
TI  - Conventional deep pressure algometry is not suitable for clinical assessment of
      nociception in painless diabetic neuropathy.
AB  - BACKGROUND: In diabetic persons with painless neuropathic foot ulceration, foot
      skin was found to be insensate to noxious pinprick stimulation (stimulation area
      less than 0.05 mm2), while compression of deep subcutaneous foot tissues by
      Algometer II(r) (stimulation area 1 cm2) could evoke a deep dull aching. To
      elucidate this discrepancy, the Algometer II stimulation technique was critically
      reviewed by varying probe sizes and anatomical sites in the same study population
      3 years later. METHODS: Ten control subjects without neuropathy and 11 persons
      with painless diabetic neuropathy (PLDN, seven of whom with diabetic foot
      syndrome, i.e., past painless foot ulcer, or inactive Charcot arthropathy) were
      re-examined using Algometer II. Deep pressure pain perception threshold (DPPPT)
      was measured in random sequence with stimulation areas of 0.5 cm2, 1 cm2, and 2
      cm2 (separated by 5 min intervals), at the plantar forefoot, the instep, and the
      hindfoot of both legs. RESULTS: In the control and PLDN groups, median DPPPTs
      differed significantly between stimulation areas (highest with 0.5 cm2,
      intermediate with 1 cm2, lowest with 2 cm2; p<0.001), and varied moderately by
      anatomical site. Between-group differences were relatively small. Results of the
      1 cm2 assessments repeated 3 years apart were similar. CONCLUSIONS: Algometer II
      readings represent spatial summation of low-threshold pressure-receptor rather
      than of high-threshold nociceptor stimulation and are, thus, unhelpful for
      assessing PLDN. Reproducibility of the measurements is good.

PMID- 27702430
TI  - Prevention literacy: community-based advocacy for access and ownership of the HIV
      prevention toolkit.
AB  - INTRODUCTION: Critical technological advances have yielded a toolkit of HIV
      prevention strategies. This literature review sought to provide contextual and
      historical reflection needed to bridge the conceptual gap between clinical
      efficacy and community effectiveness (i.e. knowledge and usage) of existing HIV
      prevention options, especially in resource-poor settings. METHODS: Between
      January 2015 and October 2015, we reviewed scholarly and grey literatures to
      define treatment literacy and health literacy and assess the current need for
      literacy related to HIV prevention. The review included searches in electronic
      databases including MEDLINE, PsycINFO, PubMed, and Google Scholar. Permutations
      of the following search terms were used: "treatment literacy," "treatment
      education," "health literacy," and "prevention literacy." Through an iterative
      process of analyses and searches, titles and/or abstracts and reference lists of
      retrieved articles were reviewed for additional articles, and historical content
      analyses of grey literature and websites were additionally conducted. RESULTS AND
      DISCUSSION: Treatment literacy was a well-established concept developed in the
      global South, which was later partially adopted by international agencies such as
      the World Health Organization. Treatment literacy emerged as more effective
      antiretroviral therapies became available. Developed from popular pedagogy and
      grassroots efforts during an intense struggle for treatment access, treatment
      literacy addressed the need to extend access to underserved communities and low
      income settings that might otherwise be excluded from access. In contrast,
      prevention literacy is absent in the recent surge of new biomedical prevention
      strategies; prevention literacy was scarcely referenced and undertheorized in the
      available literature. Prevention efforts today include multimodal techniques,
      which jointly comprise a toolkit of biomedical, behavioural, and
      structural/environmental approaches. However, linkages to community advocacy and
      mobilization efforts are limited and unsustainable. Success of prevention efforts
      depends on equity of access, community-based ownership, and multilevel support
      structures to enable usage and sustainability. CONCLUSIONS: For existing HIV
      prevention efforts to be effective in "real-world" settings, with limited
      resources, reflection on historical lessons and contextual realities (i.e.
      policies, financial constraints, and biomedical patents) indicated the need to
      extend principles developed for treatment access and treatment literacy, to
      support prevention literacy and prevention access as an integral part of the
      global response to HIV.

PMID- 27702431
TI  - Do MCAT scores predict USMLE scores? An analysis on 5 years of medical student
      data.
AB  - INTRODUCTION: The purpose of this study was to determine the associations and
      predictive values of Medical College Admission Test (MCAT) component and
      composite scores prior to 2015 with U.S. Medical Licensure Exam (USMLE) Step 1
      and Step 2 Clinical Knowledge (CK) scores, with a focus on whether students
      scoring low on the MCAT were particularly likely to continue to score low on the
      USMLE exams. METHOD: Multiple linear regression, correlation, and chi-square
      analyses were performed to determine the relationship between MCAT component and
      composite scores and USMLE Step 1 and Step 2 CK scores from five graduating
      classes (2011-2015) at the University of Minnesota Medical School (N=1,065).
      RESULTS: The multiple linear regression analyses were both significant (p<0.001).
      The three MCAT component scores together explained 17.7% of the variance in Step
      1 scores (p<0.001) and 12.0% of the variance in Step 2 CK scores (p<0.001). In
      the chi-square analyses, significant, albeit weak associations were observed
      between almost all MCAT component scores and USMLE scores (Cramer's V ranged from
      0.05 to 0.24). DISCUSSION: Each of the MCAT component scores was significantly
      associated with USMLE Step 1 and Step 2 CK scores, although the effect size was
      small. Being in the top or bottom scoring range of the MCAT exam was predictive
      of being in the top or bottom scoring range of the USMLE exams, although the
      strengths of the associations were weak to moderate. These results indicate that
      MCAT scores are predictive of student performance on the USMLE exams, but, given
      the small effect sizes, should be considered as part of the holistic view of the
      student.

PMID- 27702432
TI  - Mystery behind the match: an undergraduate medical education-graduate medical
      education collaborative approach to understanding match goals and outcomes.
AB  - BACKGROUND: There is a paucity of information regarding institutional targets for
      the number of undergraduate medical education (UME) graduates being matched to
      graduate medical education (GME) programs at their home institutions. At our
      institution, the Duke University, the number of UME graduates matched to GME
      programs declined dramatically in 2011. To better understand why this decline may
      have happened, we sought to identify perceived quality metrics for UME and GME
      learners, evaluate trends in match outcomes and educational program
      characteristics, and explore whether there is an ideal retention rate for UME
      graduates in their home institutions' GME programs. METHODS: We analyzed the
      number of Duke University UME graduates remaining at Duke for GME training over
      the past 5 years. We collected data to assess for changing characteristics of UME
      and GME, and performed descriptive analysis of trends over time to investigate
      the potential impact on match outcomes. RESULTS: A one-sample t-test analysis
      showed no statistically significant difference in the number of Duke UME
      graduates who stayed for GME training. For both UME and GME, no significant
      changes in the characteristics of either program were found. DISCUSSION: We
      created a process for monitoring data related to the characteristics or perceived
      quality of UME and GME programs and developed a shared understanding of what may
      impact match lists for both UME graduates and GME programs, leaving the Match
      somewhat less mysterious. While we understand the trend of graduates remaining at
      their home institutions for GME training, we are uncertain whether setting a goal
      for retention is reasonable, and so some mystery remains. We believe there is an
      invaluable opportunity for collaboration between UME and GME stakeholders to
      facilitate discussion about setting shared institutional goals.

PMID- 27702433
TI  - Effectiveness of hands-on tutoring and guided self-directed learning versus self
      directed learning alone to educate critical care fellows on mechanical
      ventilation - a pilot project.
AB  - BACKGROUND: Physicians require extensive training to achieve proficiency in
      mechanical ventilator (MV) management of the critically ill patients. Guided self
      directed learning (GSDL) is usually the method used to learn. However, it is
      unclear if this is the most proficient approach to teaching mechanical
      ventilation to critical care fellows. We, therefore, investigated whether
      critical care fellows achieve higher scores on standardized testing and report
      higher satisfaction after participating in a hands-on tutorial combined with GSDL
      compared to self-directed learning alone. METHODS: First-year Pulmonary and
      Critical Care Medicine (PCCM) fellows (n=6) and Critical Care Internal Medicine
      (CCIM) (n=8) fellows participated. Satisfaction was assessed using the Likert
      scale. MV knowledge assessment was performed by administering a standardized 25
      question multiple choice pre- and posttest. For 2 weeks the CCIM fellows were
      exposed to GSDL, while the PCCM fellows received hands-on tutoring combined with
      GSDL. RESULTS: Ninety-three percentage (6 PCCM and 7 CCIM fellows, total of 13
      fellows) completed all evaluations and were included in the final analysis. CCIM
      and PCCM fellows scored similarly in the pretest (64% vs. 52%, p=0.13). Following
      interventions, the posttest scores increased in both groups. However, no
      significant difference was observed based on the interventions (74% vs. 77%,
      p=0.39). The absolute improvement with the hands-on-tutoring and GSDL group was
      higher than GSDL alone (25% vs. 10%, p=0.07). Improved satisfaction scores were
      noted with hands-on tutoring. CONCLUSIONS: Hands-on tutoring combined with GSDL
      and GSDL alone were both associated with an improvement in posttest scores.
      Absolute improvement in test and satisfaction scores both trended higher in the
      hands-on tutorial group combined with GSDL group.

PMID- 27702434
TI  - RF-Burning Mouth Syndrome: New Treatments.

PMID- 27702435
TI  - Prevalence of Cancer in Adults With Congenital Heart Disease Compared With the
      General Population.
AB  - The prevalence rate of cancer among adult patients with congenital heart disease
      (CHD) in North America has not been previously described. The Quebec adult CHD
      database was used to determine the prevalence rate of cancer among adult patients
      with CHD measured as the number of adults with CHD and cancer alive in 2005 per
      1,000 adults with CHD. This prevalence rate was compared with the prevalence rate
      of cancer in the general population of adults in Canada. Types of cancer among
      the CHD group were described by gender and age. Adult patients with CHD had a 1.6
      to 2 times higher prevalence of cancer at 2, 5, and 10 years for both men and
      women. Overall, men had a greater prevalence of total cancers in all-time
      durations than did women. Breast, colon, and prostate cancer were the most common
      cancers reported in adults with CHD. In conclusion, we observed an increased
      prevalence of cancer among the adult CHD population of Quebec compared with the
      general Canadian population.

PMID- 27702436
TI  - Video-assisted thoracoscopic approach of tumors located in the thoracoabdominal
      aortic hiatus.

PMID- 27702437
TI  - Endovascular repair versus open surgery in patients in the treatment of the
      ruptured of aneurysms abdominal.
AB  - INTRODUCTION: Rupture of abdominal aortic aneurysm is still a difficult challenge
      for the vascular surgeon due to the high perioperative mortality. The aim of our
      study is to describe the characteristics of the population as well as to compare
      morbidity and mortality in patients undergoing open surgery or endovascular
      repair in our center. METHODS: Database with 82 rAAA between January 2002
      December 2014, studying two cohorts, open surgery and endovascular repair.
      Epidemiologic, clinical, surgical techniques, perioperative mortality and
      complications are analyzed. RESULTS: 82 rAAA cases were operated (men: 80, women:
      2). Mean age 72+/-9.6 years. 76.8% (63 cases) was performed by open surgery.
      BACKGROUND: smokers 59, 7%, alcoholism 19.5%, DM 10.9%, AHT: 53.6%, dyslipidemia
      30.5%. The most frequent clinical presentation was abdominal pain with lumbar
      irradiation: 50 cases (20.7% associating syncope). Overall hospital mortality was
      58.5%. Hemodynamic shock prior to intervention was associated with increased
      mortality (p <.001). Anemia, leukocytosis, aneurysm size, sex and age did not
      show a statistically significant difference with respect to mortality (p>.05).
      The presence of iliac aneurysms was associated with increased mortality (p
      <.0045). Perioperative mortality in endovascular repair was 42%, and in open
      surgery was 63.5% (p>.05). Hospital stay was lower in the endovascular group
      (p=.3859). CONCLUSIONS: Hemodynamic shock and the presence of concomitant iliac
      aneurysms have a statistically significant association with perioperative
      mortality in both groups. We found clinically significant differences in
      mortality, complications and hospital stay when comparing both groups with better
      results for EVAR, without statistically significant differences.

PMID- 27702438
TI  - Venous Air Embolism and Pars Plana Vitrectomy: Silent Co-Conspirators.

PMID- 27702439
TI  - Fixation Stability and Refractive Error After Cataract Surgery in High Myopic
      Eyes.

PMID- 27702442
TI  - Autoinflammatory diseases in adults. Clinical characteristics and prognostic
      implications.
AB  - Autoinflammatory diseases are clinical conditions with inflammatory
      manifestations that present in a periodic or persistent manner and are caused by
      acquired or hereditary disorders of the innate immune response. In general, these
      diseases are more common in childhood, but cases have been reported in adults and
      are therefore important for all specialists. There are few references on these
      diseases in adults due to their low prevalence and underdiagnosis. The aim of
      this study is to review the scientific literature on these disorders to
      systematise their clinical, prognostic and treatment response characteristics in
      adults.

PMID- 27702441
TI  - Effects of microcystin-LR and cylindrospermopsin on plant-soil systems: A review
      of their relevance for agricultural plant quality and public health.
AB  - Toxic cyanobacterial blooms are recognized as an emerging environmental threat
      worldwide. Although microcystin-LR is the most frequently documented cyanotoxin,
      studies on cylindrospermopsin have been increasing due to the invasive nature of
      cylindrospermopsin-producing cyanobacteria. The number of studies regarding the
      effects of cyanotoxins on agricultural plants has increased in recent years, and
      it has been suggested that the presence of microcystin-LR and cylindrospermopsin
      in irrigation water may cause toxic effects in edible plants. The uptake of these
      cyanotoxins by agricultural plants has been shown to induce morphological and
      physiological changes that lead to a potential loss of productivity. There is
      also evidence that edible terrestrial plants can bioaccumulate cyanotoxins in
      their tissues in a concentration dependent-manner. Moreover, the number of
      consecutive cycles of watering and planting in addition to the potential
      persistence of microcystin-LR and cylindrospermopsin in the environment are
      likely to result in groundwater contamination. The use of cyanotoxin-contaminated
      water for agricultural purposes may therefore represent a threat to both food
      security and food safety. However, the deleterious effects of cyanotoxins on
      agricultural plants and public health seem to be dependent on the concentrations
      studied, which in most cases are non-environmentally relevant. Interestingly, at
      ecologically relevant concentrations, the productivity and nutritional quality of
      some agricultural plants seem not to be impaired and may even be enhanced.
      However, studies assessing if the potential tolerance of agricultural plants to
      these concentrations can result in cyanotoxin and allergen accumulation in the
      edible tissues are lacking. This review combines the most current information
      available regarding this topic with a realistic assessment of the impact of
      cyanobacterial toxins on agricultural plants, groundwater quality and public
      health.

PMID- 27702440
TI  - Epigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings
      From the Women's Health Initiative Study.
AB  - BACKGROUND: Insomnia symptoms are associated with vulnerability to age-related
      morbidity and mortality. Cross-sectional data suggest that accelerated biological
      aging may be a mechanism through which sleep influences risk. A novel method for
      determining age acceleration using epigenetic methylation to DNA has demonstrated
      predictive utility as an epigenetic clock and prognostic of age-related morbidity
      and mortality. METHODS: We examined the association of epigenetic age and immune
      cell aging with sleep in the Women's Health Initiative study (N = 2078; mean 64.5
      +/- 7.1 years of age) with assessment of insomnia symptoms (restlessness,
      difficulty falling asleep, waking at night, trouble getting back to sleep, and
      early awakenings), sleep duration (short sleep 5 hours or less; long sleep
      greater than 8 hours), epigenetic age, naive T cell (CD8+CD45RA+CCR7+), and late
      differentiated T cells (CD8+CD28-CD45RA-). RESULTS: Insomnia symptoms were
      related to advanced epigenetic age (beta +/- SE = 1.02 +/- 0.37, p = .005) after
      adjustments for covariates. Insomnia symptoms were also associated with more late
      differentiated T cells (beta +/- SE = 0.59 +/- 0.21, p = .006), but not with
      naive T cells. Self-reported short and long sleep duration were unrelated to
      epigenetic age. Short sleep, but not long sleep, was associated with fewer naive
      T cells (p < .005) and neither was related to late differentiated T cells.
      CONCLUSIONS: Symptoms of insomnia were associated with increased epigenetic age
      of blood tissue and were associated with higher counts of late differentiated
      CD8+ T cells. Short sleep was unrelated to epigenetic age and late differentiated
      cell counts, but was related to a decline in naive T cells. In this large
      population-based study of women in the United States, insomnia symptoms are
      implicated in accelerated aging.

PMID- 27702443
TI  - Brazilian propolis promotes immunomodulation on human cells from American
      Tegumentar Leishmaniasis patients and healthy donors infected with L.
      braziliensis.
AB  - American Tegumentar Leishmaniasis (ATL) is an infectious disease caused by
      Leishmania parasites with ineffective treatment. The properties of propolis have
      been studied in different experimental studies, however, few works have
      investigated the effects of propolis on human-derived peripheral blood
      mononuclear cells (PBMC) in leishmaniasis models. Thus, we investigate the
      immunomodulatory effects of propolis treatment on PBMC from ATL patients and on
      PBMC from healthy donors infected with Leishmania braziliensis. Our data
      demonstrate that propolis pretreatment shows immunomodulatory effects on both
      healthy donors and ATL patients adherent cells, increasing IL-4 and IL-17 and
      decreasing IL-10, in either the presence or absence of the L. braziliensis
      infection, demonstrating that propolis contributes with the decrease of the
      inflammation and could also contribute with parasite control.

PMID- 27702444
TI  - Increasing ankle push-off work with a powered prosthesis does not necessarily
      reduce metabolic rate for transtibial amputees.
AB  - Amputees using passive ankle-foot prostheses tend to expend more metabolic energy
      during walking than non-amputees, and reducing this cost has been a central
      motivation for the development of active ankle-foot prostheses. Increased push
      off work at the end of stance has been proposed as a way to reduce metabolic
      energy use, but the effects of push-off work have not been tested in isolation.
      In this experiment, participants with unilateral transtibial amputation (N=6)
      walked on a treadmill at a constant speed while wearing a powered prosthesis
      emulator. The prosthesis delivered different levels of ankle push-off work across
      conditions, ranging from the value for passive prostheses to double the value for
      non-amputee walking, while all other prosthesis mechanics were held constant.
      Participants completed six acclimation sessions prior to a data collection in
      which metabolic rate, kinematics, kinetics, muscle activity and user satisfaction
      were recorded. Metabolic rate was not affected by net prosthesis work rate
      (p=0.5; R2=0.007). Metabolic rate, gait mechanics and muscle activity varied
      widely across participants, but no participant had lower metabolic rate with
      higher levels of push-off work. User satisfaction was affected by push-off work
      (p=0.002), with participants preferring values of ankle push-off slightly higher
      than in non-amputee walking, possibly indicating other benefits. Restoring or
      augmenting ankle push-off work is not sufficient to improve energy economy for
      lower-limb amputees. Additional necessary conditions might include alternate
      timing or control, individualized tuning, or particular subject characteristics.

PMID- 27702445
TI  - Forensic sciences (anthropology/archaeology/pathology) and international criminal
      justice.

PMID- 27702446
TI  - The effect of mark enhancement techniques on the subsequent detection of saliva.
AB  - There appears to be a limited but growing body of research on the sequential
      analysis/treatment of multiple types of evidence. The development of an
      integrated forensic approach is necessary to maximise evidence recovery and to
      ensure that a particular treatment is not detrimental to other types of evidence.
      This study aims to assess the effect of latent and blood mark enhancement
      techniques (e.g. fluorescence, ninhydrin, acid violet 17, black iron-oxide powder
      suspension) on the subsequent detection of saliva. Saliva detection was performed
      by means of a presumptive test (Phadebas(r)) in addition to analysis by a rapid
      stain identification (RSID) kit test and confirmatory DNA testing. Additional
      variables included a saliva depletion series and a number of different substrates
      with varying porosities as well as different ageing periods. Examination and
      photography under white light and fluorescence was carried out prior to and after
      chemical enhancement. All enhancement techniques (except Bluestar(r) Forensic
      Magnum luminol) employed in this study resulted in an improved visualisation of
      the saliva stains, although the inherent fluorescence of saliva was sometimes
      blocked after chemical treatment. The use of protein stains was, in general,
      detrimental to the detection of saliva. Positive results were less pronounced
      after the use of black iron-oxide powder suspension, cyanoacrylate fuming
      followed by BY40 and ninhydrin when compared to the respective positive controls.
      The application of Bluestar(r) Forensic Magnum luminol and black magnetic powder
      proved to be the least detrimental, with no significant difference between the
      test results and the positive controls. The use of non-destructive fluorescence
      examination provided good visualisation; however, only the first few marks in the
      depletion were observed. Of the samples selected for DNA analysis only depletion
      1 samples contained sufficient DNA quantity for further processing using standard
      methodology. The 28-day delay between sample deposition and collection resulted
      in a 5-fold reduction in the amount of useable DNA. When sufficient DNA
      quantities were recovered, enhancement techniques did not have a detrimental
      effect on the ability to generate DNA profiles. This study aims to contribute to
      a strategy for maximising evidence recovery and efficiency for the detection of
      latent marks and saliva. The results demonstrate that most of the enhancement
      techniques employed in this study were not detrimental to the subsequent
      detection of saliva by means of presumptive, confirmative and DNA tests.

PMID- 27702447
TI  - A method for rapid sampling and characterization of smokeless powder using
      sorbent-coated wire mesh and direct analysis in real time - mass spectrometry
      (DART-MS).
AB  - Improvised explosive devices (IEDs) are often used by terrorists and criminals to
      create public panic and destruction, necessitating rapid investigative
      information. However, backlogs in many forensic laboratories resulting in part
      from time-consuming GC-MS and LC-MS techniques prevent prompt analytical
      information. Direct analysis in real time - mass spectrometry (DART-MS) is a
      promising analytical technique that can address this challenge in the forensic
      science community by permitting rapid trace analysis of energetic materials.
      Therefore, we have designed a qualitative analytical approach that utilizes novel
      sorbent-coated wire mesh and dynamic headspace concentration to permit the
      generation of information rich chemical attribute signatures (CAS) for trace
      energetic materials in smokeless powder with DART-MS. Sorbent-coated wire mesh
      improves the overall efficiency of capturing trace energetic materials in
      comparison to swabbing or vacuuming. Hodgdon Lil' Gun smokeless powder was used
      to optimize the dynamic headspace parameters. This method was compared to
      traditional GC-MS methods and validated using the NIST RM 8107 smokeless powder
      reference standard. Additives and energetic materials, notably nitroglycerin,
      were rapidly and efficiently captured by the Carbopack X wire mesh, followed by
      detection and identification using DART-MS. This approach has demonstrated the
      capability of generating comparable results with significantly reduced analysis
      time in comparison to GC-MS. All targeted components that can be detected by GC
      MS were detected by DART-MS in less than a minute. Furthermore, DART-MS offers
      the advantage of detecting targeted analytes that are not amenable to GC-MS. The
      speed and efficiency associated with both the sample collection technique and
      DART-MS demonstrate an attractive and viable potential alternative to
      conventional techniques.

PMID- 27702448
TI  - Laser ablation coupled with DAPNe-NSI-MS applied to redacted documents.
AB  - Laser ablation has been applied to redacted documents, where the text has been
      concealed by other ink. This technique strips the redacting ink revealing the
      text that was once redacted. Once removed, a nanomanipulation technique is used
      to extract the ink of the underlying text where mass spectrometry is then
      implemented to analyze its ink chemistry. In order to facilitate microscopy with
      direct analyte-probed nanoextraction coupled to nanospray ionization mass
      spectrometry (DAPNe-NSI-MS), laser ablation must be executed prior to ink
      extraction. Laser ablation has a nondestructive approach of stripping the ink
      used to redact the document. Not only does this reveal the text, it clears an
      area for DAPNe to directly extract ink, in miniscule amounts, from the document
      without inducing destruction. The redacting ink was concluded to affect the aging
      process of the concealed handwritten ink more than the printed text. The redacted
      handwritten sample obtained higher relative peak area (%) values than the control
      samples (text that was not redacted) and the control for the printed text
      produced higher amounts of low molecular weight products than the sample.
      Implementing laser ablation on these samples could also affect the chemical
      properties of the underlying ink due to the additional UV radiation and plasma
      heating. Results indicate by using laser ablation to remove the redacting ink,
      the relative peak area of the underlying ink deviates by 1.25%. The thermal
      degradation of binding agents such as polymethylene, polyethylene glycol, and
      diethylene glycol was monitored by calculating the relative peak area for five
      days which, in turn, tracks the oxidation process. The relative peak area values
      were also used to determine the chemical kinetics of polyethylene glycol, where
      degradation and polymerization occur.

PMID- 27702449
TI  - Shoeprint retrieval: Core point alignment for pattern comparison.
AB  - PURPOSE: Shoeprint recognition has been widely used as forensic evidence in
      criminal cases. The purpose of this study is to propose a shoeprint retrieval
      method based on core point alignment for pattern analysis. METHOD: The proposed
      method firstly detects contour points in a black-and-white shoeprint image. These
      reliable contour points are selected to simulate the left and right sidelines of
      the shoeprint by a curve fitting method. Subsequently, the most concave points
      along the left and right sidelines can determine the core point of the shoeprint,
      thereby partitioning the shoeprint into circular regions. Next, the Zernike
      moments of the circular regions are calculated for pattern descriptions of each
      region. Finally, the Euclidean distance is measured to match the shoeprints with
      the same pattern. RESULT: The highest APR=0.726 is obtained from the first four
      Zernike moments with a radius of 90pixels and three baselines. The experimental
      results also show that the Zernike method in any order always outperforms the
      compared moment invariant and GLCM method. The experimental results also indicate
      that the core point is more stable than the gravity center in the both sets,
      because the standard deviation values of the core point are less than that of the
      gravity center. CONCLUSIONS: This study has verified that the proposed method can
      effectively align shoeprints for pattern comparison.

PMID- 27702450
TI  - The identification of emotions from gait.

PMID- 27702451
TI  - Sex estimation from the scapula in a contemporary Chilean population.
AB  - The scapula is valuable for sex estimation in human skeletons. Muscles provide
      protection to the scapula making it difficult to fracture, therefore increasing
      the potential for undamaged scapulae at forensic scenes. The goal of this project
      is to evaluate the accuracy of discriminant functions, created using an
      indigenous Guatemalan and contemporary Mexican population, when applied to a
      contemporary Chilean sample for estimation of sex from the scapula. The length of
      the glenoid cavity (LGC) and breadth of the glenoid cavity (BGC) were measured.
      The sample included 114 individuals (58 males and 56 females) with age ranges
      from 17 to 85years old. When the Guatemalan discriminant functions were applied
      to the Chilean sample they showed higher accuracy rates for sexing male scapulae
      (89.6% to 94.8%) than for sexing female scapulae (53.4% to 80.3%). When the
      Mexican discriminant functions were applied to the Chilean sample they showed
      higher accuracy rates for sexing female scapulae (82.1% to 96.4%) than for sexing
      male scapulae (56.9% to 89.6%). Size comparisons were made to a Guatemalan,
      Mexican, White American, and Greek population. Overall, in males and females of
      the Chilean population both left and right scapulae were larger than in the
      Guatemalan population but smaller than in the Mexican, White American, and Greek
      samples. Population-specific discriminant functions were created for the Chilean
      population with an overall sex classification accuracy rate of 80.7% to 86.0%.

PMID- 27702452
TI  - Discussion on how to implement a verbal scale in a forensic laboratory: Benefits,
      pitfalls and suggestions to avoid misunderstandings.
AB  - In a recently published guideline for evaluative reporting in forensic science,
      the European Network of Forensic Science Institutes (ENFSI) recommended the use
      of the likelihood ratio for the measurement of the value of forensic results. As
      a device to communicate the probative value of the results, the ENFSI guideline
      mentions the possibility to define and use a verbal scale, which should be
      unified within a forensic institution. This paper summarizes discussions held
      between scientists of our institution to develop and implement such a verbal
      scale. It intends to contribute to general discussions likely to be faced by any
      forensic institution that engages in continuous monitoring and improving of their
      evaluation and reporting format. We first present published arguments in favour
      of the use of such verbal qualifiers. We emphasise that verbal qualifiers do not
      replace the use of numbers to evaluate forensic findings, but are useful to
      communicate the probative value, since the weight of evidence in terms of
      likelihood ratio are still apprehended with difficulty by both the forensic
      scientists, especially in the absence of hard data, and the recipient of
      information. We further present arguments that support the development of the
      verbal scale that we propose. Recognising the limits of the use of such a verbal
      scale, we then discuss its disadvantages: it may lead to the spurious view
      according to which the value of the observations made in a given case is relative
      to other cases. Verbal qualifiers are also prone to misunderstandings and cannot
      be coherently combined with other evidence. We therefore recommend not using the
      verbal qualifier alone in a written statement. While scientists should only
      report on the probability of the findings - and not on the probability of the
      propositions, which are the duty of the Court - we suggest showing examples to
      let the recipient of information understand how the scientific evidence affects
      the probabilities of the propositions. To avoid misunderstandings, we also advise
      to mention in the statement what the results do not mean. Finally, we are of the
      opinion that if experts were able to coherently articulate numbers, and if
      recipients of information could properly handle such numbers, then verbal
      qualifiers could be abandoned completely. At that time, numerical expressions of
      probative value will be appropriately understood, as other numerical measures
      that most of us understand without the need of any further explanation, such as
      expressions for length or temperature.

PMID- 27702453
TI  - Special issue on measuring and reporting the precision of forensic likelihood
      ratios: Introduction to the debate.
AB  - The present paper introduces the Science & Justice virtual special issue on
      measuring and reporting the precision of forensic likelihood ratios - whether
      this should be done, and if so how. The focus is on precision (aka reliability)
      as opposed to accuracy (aka validity). The topic is controversial and different
      authors are expected to express a range of nuanced opinions. The present paper
      frames the debate, explaining the underlying problem and referencing classes of
      solutions proposed in the existing literature. The special issue will consist of
      a number of position papers, responses to those position papers, and replies to
      the responses.

PMID- 27702454
TI  - What should a forensic practitioner's likelihood ratio be?
AB  - We argue that forensic practitioners should empirically assess and report the
      precision of their likelihood ratios. Once the practitioner has specified the
      prosecution and defence hypotheses they have adopted, including the relevant
      population they have adopted, and has specified the type of measurements they
      will make, their task is to empirically calculate an estimate of a likelihood
      ratio which has a true but unknown value. We explicitly reject the competing
      philosophical position that the forensic practitioner's likelihood ratio should
      be based on subjective personal probabilities. Estimates of true but unknown
      values are based on samples and are subject to sampling uncertainty, and it is
      standard practice to report the degree of precision of such estimates. We discuss
      the dangers of not reporting precision to the courts, and the problems with an
      alternative approach which instead reports a verbal expression corresponding to a
      pre-specified range of likelihood ratio values. Reporting precision as an
      interval requires an arbitrary choice of coverage, e.g., a 95% or a 99% credible
      interval. We outline a normative framework which a trier of fact could employ to
      make non-arbitrary use of the results of forensic practitioners' empirical
      calculations of likelihood ratios and their precision.

PMID- 27702455
TI  - Admitting to uncertainty in the LR.
AB  - In this paper I argue that, given our current state of knowledge, reporting
      uncertainty in the likelihood ratio is best practice. This may in time be
      replaced by reporting a Bayes factor, but we are currently unable to do this in
      all but the simplest of examples.

PMID- 27702456
TI  - An argument against presenting interval quantifications as a surrogate for the
      value of evidence.
AB  - In the various forensic science disciplines, recent analytical developments
      paired with modern statistical computational tools have led to the proliferation
      of adhoc techniques for quantifying the probative value of forensic evidence.
      Many legal and scientific scholars agree that the value of evidence should be
      reported as a likelihood ratio or a Bayes Factor. Quantifying the probative value
      of forensic evidence is subjected to many sources of variability and uncertainty.
      There is currently a debate on how to characterize the reliability of the value
      of evidence. Some authors have proposed associating a confidence/credible
      interval with the value of evidence assigned to a collection of forensic
      evidence. In this paper, we will discuss the reasons for our opinion that
      interval quantifications for the value of evidence should not be used directly in
      the Bayesian decision-making process to determine the support of the evidence for
      one of the two competing hypotheses.

PMID- 27702457
TI  - The LR does not exist.
AB  - More than 40years ago, De Finetti warned that probability is a misleading
      misconception when regarded as objectively existing exterior to the mind.
      According to De Finetti, probabilities are necessarily subjective, and quantify
      our belief in the truth of events in the real world. Given evidence of a shared
      feature of a trace and an accused, we apply this framework to assign an
      evidential value to this correspondence. Dividing 1 by the objectively existing
      proportion of the population sharing that feature would give that evidential
      value - expressed as a likelihood ratio (LR) - only if that proportion were
      known. As in practice the proportion can only be estimated, this leads some to
      project their sampling uncertainty - or precision - associated with the estimated
      proportion onto the likelihood ratio, and to report an interval. Limited data
      should limit our LR however, because as we will demonstrate the LR is given by
      what we know about the proportion rather than by the unknown proportion itself.
      Encapsulating all uncertainty - including sampling uncertainty of the proportion 
      our LR reflects how much information we have retrieved from the feature
      regarding the trace's origin, based on our present knowledge. Not an interval but
      a number represents this amount of information, equal to the logarithm of the LR.
      As long as we know how to interpret the evidence with a well-defined
      probabilistic model, we know what our evidence is worth.

PMID- 27702458
TI  - Reframing the debate: A question of probability, not of likelihood ratio.
AB  - Evidential value is measured by a likelihood ratio. This ratio has two
      components, the probability, or probability density, of the evidence if the
      prosecution proposition is true and the probability (density) of the evidence if
      the defence proposition is true. It takes the form of a single value, even if
      these probabilities are subjective measures of belief of the reporting forensic
      scientist.

PMID- 27702459
TI  - Posterior distributions for likelihood ratios in forensic science.
AB  - Evaluation of evidence in forensic science is discussed using posterior
      distributions for likelihood ratios. Instead of eliminating the uncertainty by
      integrating (Bayes factor) or by conditioning on parameter values, uncertainty in
      the likelihood ratio is retained by parameter uncertainty derived from posterior
      distributions. A posterior distribution for a likelihood ratio can be summarised
      by the median and credible intervals. Using the posterior mean of the
      distribution is not recommended. An analysis of forensic data for body height
      estimation is undertaken. The posterior likelihood approach has been criticised
      both theoretically and with respect to applicability. This paper addresses the
      latter and illustrates an interesting application area.

PMID- 27702460
TI  - Using sensitivity analyses in Bayesian Networks to highlight the impact of data
      paucity and direct future analyses: a contribution to the debate on measuring and
      reporting the precision of likelihood ratios.
AB  - Bayesian networks are being increasingly used to address complex questions of
      forensic interest. Like all probabilities, those that underlie the nodes within a
      network rely on structured data and knowledge. Obviously, the more structured
      data we have, the better. But, in real life, the numbers of experiments that can
      be carried out are limited. It is thus important to know if/when our knowledge is
      sufficient and when one needs to perform further experiments to be in a position
      to report the value of the observations made. To explore the impact of the amount
      of data that are available for assessing results, we have constructed Bayesian
      Networks and explored the sensitivity of the likelihood ratios to changes to the
      data that underlie each node. Bayesian networks are constructed and sensitivity
      analyses performed using freely available R libraries (gRain and BNlearn). We
      demonstrate how the analyses can be used to yield information about the
      robustness provided by the data used to inform the conditional probability table,
      and also how they can be used to direct further research for maximum effect. By
      maximum effect, we mean to contribute with the least investment to an increased
      robustness. In addition, the paper investigates the consequences of the
      sensitivity analysis to the discussion on how the evidence shall be reported for
      a given state of knowledge in terms of underpinning data.

PMID- 27702461
TI  - [We carry on advancing and growing].

PMID- 27702462
TI  - Molecular and Systems Integration of Genomic and Nongenomic Steroid Hormone
      Action.

PMID- 27702463
TI  - Retraction notice to 'Does ovarian stimulation for IVF increase gynaecological
      cancer risk? A systematic review and meta-analysis' [Reproductive BioMedicine
      Online 31 (2015) 20-29].
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 Editor-in-Chief. The authors have plagiarized
      part of a paper that had already appeared in Hum. Reprod. Update, Volume 19
      (2013) 105-123http://dx.doi.org/10.1093/humupd/dms051. One of the conditions of
      submission of a paper for publication is that authors declare explicitly that
      their work is original and has not appeared in a publication elsewhere. Re-use of
      any data should be appropriately cited. As such this article represents a severe
      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- 27702464
TI  - 3D printing-assisted osteotomy treatment for the malunion of lateral tibial
      plateau fracture.
AB  - INTRODUCTION: Osteotomy and internal fixation are usually the most effective way
      to treat the malunion of lateral tibial plateau fractures, and the accuracy of
      the osteotomy is still a challenge for surgeons. This is a report of a series of
      prospectively study of osteotomy treatment for the malunion of lateral plateau
      fractures with the aid of 3D printing technology. METHODS: A total of 7 patients
      with malunion of lateral tibial plateau fractures were enrolled in the study
      between September 2012 to September 2014 and completed follow up. CT image data
      were used for 3D reconstruction, and individually 3D printed models were used for
      accurate measurements and detail osteotomy procedures planning. Under the
      premeditated operation plan, the osteotomy operations were performed. Patients
      were invited for follow-up examinations at 2 and 6 weeks and then at intervals of
      6 to 8 weeks until 12 months or more. RESULTS: Mean age of the patients was 44
      years (range 30-52 years), 3 cases were result of fall injuries, 2 were traffic
      accidents and 2 were sports injuries. Among the cases, one accompanied with
      craniocerebra trauma, one with pelvic fracture, one accompanied with both.
      According to the Schatzker Tibial Plateau classification, the original fracture
      type were 3 type I, 1 type II and 3 type III. The lateral tibial plateau collapse
      ranges from 4 mm-12mm, with an average of 9.4mm. All the operations were
      successfully completed, the average operation time was 77.1min (range 70-90 min),
      the average intraoperative blood loss was 121.4ml (range 90-180ml), the mean
      follow-up time was 14.4 months (range 12-18 months), and the average healing time
      of the osteotomy fragments was 12 weeks (range 11-13 weeks). The difference
      between preoperative and postoperative Rasmussen scores were statistically
      significant (P<0.05). All the patients were obtained functional recovery, with no
      complications. CONCLUSION: 3D printing technology is helpful to accurately design
      osteotomy operation, reduce the risk of postoperative deformity, decrease
      intraoperative blood loss, shorten the operation time, and can effectively
      improve the treatment effect.

PMID- 27702465
TI  - Evaluation and Management of Sleep Disorders in the Hand Surgery Patient.
AB  - Despite posing a significant public health threat, sleep disorders remain poorly
      understood and often underdiagnosed and mismanaged. Although sleep disorders are
      seemingly unrelated, hand surgeons should be mindful of these because numerous
      conditions of the upper extremity have known associations with sleep disturbances
      that can adversely affect patient function and satisfaction. In addition,
      patients with sleep disorders are at significantly higher risk for severe, even
      life-threatening medical comorbidities, further amplifying the role of hand
      surgeons in the recognition of this condition.

PMID- 27702466
TI  - Erratum.

PMID- 27702467
TI  - Correlating Median Nerve Cross-sectional Area With Nerve Conduction Studies.
AB  - PURPOSE: To determine whether there is a correlation between the cross-sectional
      area (CSA) of the median nerve, as measured using ultrasound, and the distal
      motor and/or sensory latencies as measured on nerve conduction studies. METHODS:
      Patients with clinical signs and symptoms of carpal tunnel syndrome were
      prospectively enrolled in this study. Subjects underwent ultrasound measurement
      of the CSA of the median nerve at the carpal tunnel inlet by a fellowship-trained
      hand surgeon, followed by nerve conduction studies (NCS) by a certified
      electrodiagnostic technician who was blinded to the results of the ultrasound
      examination. Pearson correlations were performed to compare CSA and NCS. RESULTS:
      Pearson correlation was r = 0.57 between CSA and distal motor latency and r =
      0.47 between CSA and distal sensory latency. Correlation was r = 0.81 between
      distal motor latency and distal sensory latency. CONCLUSIONS: There is a
      correlation between CSA of the median nerve and NCS. Further research is
      necessary to determine which test correlates better with patient symptoms and
      function. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

PMID- 27702469
TI  - A new generation approach in enzyme immobilization: Organic-inorganic hybrid
      nanoflowers with enhanced catalytic activity and stability.
AB  - Many different micro and nano sized materials have been used for enzymes
      immobilization in order to increase their catalytic activity and stability.
      Generally, immobilized enzymes with conventional immobilization techniques
      exhibit improved stability while their activity is lowered compared to free
      enzymes. Recently, an elegant immobilization approach was discovered in synthesis
      of flower-like organic-inorganic hybrid nanostructures with extraordinary
      catalytic activity and stability. In this novel immobilization strategy, proteins
      (enzymes) and metal ions acted as organic and inorganic components, respectively
      to form hybrid nanoflowers (hNFs). It is demonstrated that the hNFs highly
      enhanced catalytic activities and stability in a wide range of experimental
      conditions (pHs, temperatures and salt concentration, etc.) compared to free and
      conventionally immobilized enzymes. This review mainly discussed the synthesis,
      characterization, development and applications of organic-inorganic hybrid
      nanoflowers formed of various enzymes and metal ions and explained potential
      mechanism underlying enhanced catalytic activity and stability.

PMID- 27702468
TI  - Electrospun polyvinyl alcohol/bovine serum albumin biocomposite membranes for
      horseradish peroxidase immobilization.
AB  - Electrospinning, a simple and versatile method to fabricate nanofibrous supports,
      has attracted attention in the field of enzyme immobilization. Biocomposite
      nanofibers were fabricated from mixed PVA/BSA solution and the effects of
      glutaraldehyde treatment, initial BSA concentration and PVA concentration on
      protein loading were investigated. Glutaraldehyde cross-linking significantly
      decreased protein release from nanofibers and BSA loading reached as high as
      27.3% (w/w). In comparison with the HRP immobilized into the nascent nanofibrous
      membrane, a significant increase was observed in the activity retention of the
      enzyme immobilized into the PVA/BSA biocomposite nanofibers. The immobilized HRP
      was able to tolerate much higher concentrations of hydrogen peroxide than the
      free enzyme and thus the immobilized enzyme did not demonstrate substrate
      inhibition. The immobilized HRP retained~50% of the free enzyme activity at 6.4mM
      hydrogen peroxide and no significant variation was observed in the KM value of
      the enzyme for hydrogen peroxide after immobilization. In addition, reusability
      tests showed that the residual activity of the immobilized HRP were 73% after 11
      reuse cycles. Together, these results demonstrate efficient immobilization of HRP
      into electrospun PVA/BSA biocomposite nanofibers and provide a promising
      immobilization strategy for biotechnological applications.

PMID- 27702470
TI  - Improved efficiency of a novel methyl parathion hydrolase using consensus
      approach.
AB  - A methyl parathion hydrolase (MPH) gene, bjmpd, was cloned from a newly isolated
      MP-degrading bacterial strain, Burkholderia jiangsuensis MP-1T and heterologously
      expressed in Escherichia coli BL21 (DE3). Although the amino acid sequence of the
      bjmpd-encoded enzyme, named BjMPH, differed from that of MPH from Pseudomonas sp.
      WBC-3 (PsMPH) in only three residues, Ser132, Val247 and Ala267, a significantly
      higher specific activity towards MP was exhibited by BjMPH than PsMPH. Among
      them, Ala267 was identified as a key site affecting the catalytic efficiency, and
      it was rather conservative (Ala or Ser) in homologous proteins, suggesting that a
      simple substitution of the residue in conservative site with another conservative
      residue based on the consensus sequence approach might possibly enhance the
      catalytic efficiency of the MP-degrading enzyme. Inspired by such an observation,
      we identified a new mutant, BjMPHT64N, exhibiting 3.78-fold higher catalytic
      efficiency (kcat/KM) towards MP than its wild-type, reaching 4.20*106M-1s-1. The
      mutant BjMPHT64N also displayed enhanced reactivities (kcat/KM) towards other
      organophosphorus pesticides. Homology-modelling analysis indicates that enhanced
      polar contacts of the 64th residue in this mutant may contribute to stabilizing
      the structure of the enzyme and promote the interactions between enzyme and
      substrate. This study generated an efficient MP-degrading enzyme, and provides
      useful information for enhancing the catalytic efficiency of MPHs via
      conservative residue substitution based on the consensus approach.

PMID- 27702471
TI  - Characterization of a Cellulomonas fimi exoglucanase/xylanase-endoglucanase gene
      fusion which improves microbial degradation of cellulosic biomass.
AB  - Effective degradation of cellulose requires multiple classes of enzyme working
      together. However, naturally occurring cellulases with multiple catalytic domains
      seem to be rather rare in known cellulose-degrading organisms. A fusion protein
      made from Cellulomonas fimi exo- and endo- glucanases, Cex and CenA which
      improves breakdown of cellulose is described. A homologous carbohydrate binding
      module (CBM-2) present in both glucanases was fused to give a fusion protein
      CxnA. CxnA or unfused constructs (Cex+CenA, Cex, or CenA) were expressed in
      Escherichia coli and Citrobacter freundii. The latter recombinant strains were
      cultured at the expense of cellulose filter paper. The expressed CxnA had both
      exo- and endo- glucanase activities. It was also exported to the supernatant as
      were the non-fused proteins. In addition, the hybrid CBM from the fusion could
      bind to microcrystalline cellulose. Growth of C. freundii expressing CxnA was
      superior to that of cells expressing the unfused proteins. Physical degradation
      of filter paper was also faster with the cells expressing fusion protein than the
      other constructs. Our results show that fusion proteins with multiple catalytic
      domains can improve the efficiency of cellulose degradation. Such fusion proteins
      could potentially substitute cloning of multiple enzymes as well as improving
      product yields.

PMID- 27702472
TI  - Evaluation of cysteine ethyl ester as efficient inducer for glutathione
      overproduction in Saccharomyces spp.
AB  - Economical yeast based glutathione (GSH) production is a process that is
      influenced by several factors like raw material and production costs, biomass
      production and efficient biotransformation of adequate precursors into the final
      product GSH. Nowadays the usage of cysteine for the microbial conversion into GSH
      is industrial state of practice. In the following study, the potential of
      different inducers to increase the GSH content was evaluated by means of design
      of experiments methodology. Investigations were executed in three natural
      Saccharomyces strains, S. cerevisiae, S. bayanus and S. boulardii, in a well
      suited 50ml shake tube system. Results of shake tube experiments were confirmed
      in traditional baffled shake flasks and finally via batch cultivation in lab
      scale bioreactors under controlled conditions. Comprehensive studies showed that
      the usage of cysteine ethyl ester (CEE) for the batch-wise biotransformation into
      GSH led up to a more than 2.2 times higher yield compared to cysteine as inducer.
      Additionally, the intracellular GSH content could be significantly increased for
      all strains in terms of 2.29+/-0.29% for cysteine to 3.65+/-0.23% for CEE,
      respectively, in bioreactors. Thus, the usage of CEE provides a highly attractive
      inducing strategy for the GSH overproduction.

PMID- 27702473
TI  - Using directed evolution to improve hydrogen production in chimeric hydrogenases
      from Clostridia species.
AB  - Hydrogenases are enzymes that play a key role in controlling excess reducing
      equivalents in both photosynthetic and anaerobic organisms. This enzyme is viewed
      as potentially important for the industrial generation of hydrogen gas; however,
      insufficient hydrogen production has impeded its use in a commercial process.
      Here, we explore the potential to circumvent this problem by directly evolving
      the Fe-Fe hydrogenase genes from two species of Clostridia bacteria. In addition,
      a computational model based on these mutant sequences was developed and used as a
      predictive aid for the isolation of enzymes with even greater efficiency in
      hydrogen production. Two of the improved mutants have a logarithmic increase in
      hydrogen production in our in vitro assay. Furthermore, the model predicts
      hydrogenase sequences with hydrogen productions as high as 540-fold over the
      positive control. Taken together, these results demonstrate the potential of
      directed evolution to improve the native bacterial hydrogenases as a first step
      for improvement of hydrogenase activity, further in silico prediction, and
      finally, construction and demonstration of an improved algal hydrogenase in an in
      vivo assay of C. reinhardtii hydrogen production.

PMID- 27702474
TI  - Enhanced catalytic efficiency of endo-beta-agarase I by fusion of carbohydrate
      binding modules for agar prehydrolysis.
AB  - Recently, Microbulbifer thermotolerans JAMB-A94 endo-beta-agarase I was expressed
      as catalytic domain (GH16) without a carbohydrate-binding module (CBM). In this
      study, we successfully constructed different fusions of GH16 with its original
      CBM6 and CBM13 derived from Catenovulum agarivorans. The optimum temperature and
      pH for fusions GH16-CBM6, GH16-CBM13, GH16-CBM6-CBM13 and GH16-CBM13-CBM6 were
      similar to GH16, at 55 degrees C and pH 7. All the constructed fusions
      significantly enhanced the GH16 affinity (Km) and the catalytic efficiency
      (Kcat/Km) toward agar. Among them, GH16-CBM6-CBM13 exhibited the highest
      agarolytic activity, for which Km decreased from 3.67 to 2.11mg/mL and Kcat/Km
      increased from 98.6 (mg/mL)-1sec-1 to 400.6 (mg/mL)-1sec-1. Moreover, all fusions
      selectively increased GH16 binding ability to agar, in which the highest binding
      ability of 95% was obtained with fusion GH16-CBM6-CBM13. Melted agar was
      prehydrolyzed with GH16-CBM6-CBM13, resulting in a degree of liquefaction of
      45.3% and reducing sugar yield of 14.2%. Further addition of Saccharophagus
      degradans agarolytic enzymes resulted in mono-sugar yields of 35.4% for galactose
      and 31.5% for 3,6-anhydro-l-galactose. There was no pH neutralization step
      required and no 5-hydroxymethylfurfural detected, suggesting the potential of a
      new enzymatic prehydrolysis process for efficient production of bio-products such
      as biofuels.

PMID- 27702475
TI  - Overproduction and characterization of a lytic polysaccharide monooxygenase in
      Bacillus subtilis using an assay based on ascorbate consumption.
AB  - Lytic polysaccharide monooxygenases (LPMOs) are copper ion-containing enzymes
      that degrade crystalline polysaccharides, such as cellulose or chitin, through an
      oxidative mechanism. To the best of our knowledge, there are no assay methods for
      the direct characterization of LPMOs that degrade substrates without coupled
      enzymes. As such, in this study, a coupled enzyme-free assay method for LPMOs was
      developed, which is based on measuring the consumption of ascorbic acid used as
      an external electron donor for LPMOs. To establish this new assay method, a
      chitin-active LPMO from Bacillus atrophaeus (BatLPMO10) was cloned as a model
      enzyme. An expression system using B. subtilis as the host cell yielded a simple
      purification process without complicated periplasmic fractionation, as well as
      improved productivity by 3.7-fold higher than that of Escherichia coli BL21(DE3).
      At the optimum pH determined using a newly developed assay, BatLPMO10 showed the
      highest activity in terms of promoting chitin degradation by a chitinase. In
      addition, the assay method indicated that BatLPMO10 was inhibited by sodium ions,
      and BatLPMO10 and a chitinase mutually enhanced each other's activities upon
      degrading chitin as the substrate. In conclusion, this hydrolase-free ascorbate
      assay allows quantitative analysis of BatLPMO10 without a coupled enzyme.

PMID- 27702477
TI  - Identification of a novel cellulose-binding domain within the endo-beta-1,4
      xylanase KRICT PX-3 from Paenibacillus terrae HPL-003.
AB  - The model 3-D structure of xylanase KRICT PX3 (JF320814) identified by DNA
      sequence analysis revealed a catalytic domain and CBM4-9 which functions as a
      xylan binding domain (XBD). To identify its role in xylan hydrolysis, six
      expression plasmids were constructed encoding the N-terminal CBM plus the
      catalytic domain or different glycosyl hydrolases, and the biochemical properties
      of the recombinant enzymes were compared to the original structure of PX3
      xylanase. All six of the recombinant xylanases with the addition of CBM in the
      pIVEX-GST expression vector showed no improved PX3 hydrolytic activity. However,
      the absence of the CBM domain resulted in a decrement of 40% in thermostability,
      movement of the optimal temperature from 55 degrees C to 45 degrees C, alteration
      of the optimal pH range from 5-10 to 6-8, and reduction of the enzymatic activity
      to one-second under the same condition, respectively. The putative XBD in PX3
      comprises a new N-terminal domain homologous to the catalytic thermostabilizing
      domains from other xylanases. Analysis of the main products released from xylan
      indicate that the recombinant enzymes act as endo-1,4-beta-xylanases but differ
      in their hydrolysis of xylan from beech wood, birch wood, and oat spelt.

PMID- 27702476
TI  - Production of steviol from steviol glucosides using beta-glycosidase from
      Sulfolobus solfataricus.
AB  - Steviol is a diterpene isolated from the plant Stevia rebaudiana that has a
      potential role as an antihyperglycemic agent by stimulating insulin secretion
      from pancreatic beta cells and also has significant potential to diminish the
      renal clearance of anionic drugs and their metabolites. In this study, the lacS
      gene, which encodes a thermostable beta-glycosidase (SSbgly) enzyme from the
      extremely thermoacidophillic archaeon Sulfolobus solfataricus, was cloned and
      expressed in E. coli Rossetta BL21(DE3)pLyS using lactose as an inducer. Through
      fermentation, SSbgly was expressed as a 61kDa protein with activity of 24.3U/mg
      and the OD600 of 23 was reached after 18h induction with 10mM lactose. Purified
      protein was obtained by Ni-Sepharose chromatography with a yield of 92.3%. SSbgly
      hydrolyzed steviol glycosides to produce steviol with a yield of 99.2%. The
      optimum conditions for steviol production were 50U/ml SSbgly and 90mg/ml Ste at
      75 degrees C as determined by the response surface method.

PMID- 27702479
TI  - Enhancing activity and thermostability of lipase A from Serratia marcescens by
      site-directed mutagenesis.
AB  - Lipases as significant biocatalysts had been widely employed to catalyze various
      chemical reactions such as ester hydrolysis, ester synthesis, and
      transesterification. Improving the activity and thermostability of enzymes is
      desirable for industrial applications. The lipase of Serratia marcescens
      belonging to family I.3 lipase has a very important pharmaceutical application in
      production of chiral precursors. In the present study, to achieve improved lipase
      activity and thermostability, using computational predictions of protein, four
      mutant lipases of SML (MutG2P, MutG59P, Mut H279K and MutL613WA614P) were
      constructed by site-directed mutagenesis. The recombinant mutant proteins were
      over-expressed in E. coli and purified by affinity chromatography on the Ni-NTA
      system. Circular dichroism spectroscopy, differential scanning calorimetry and
      kinetic parameters (Km and kcat) were determined. Our results have shown that the
      secondary structure of all lipases was approximately similar to one another. The
      MutG2P and MutG59P were more stable than wild type by approximately 2.3 and 2.9
      in T1/2, respectively. The catalytic efficiency (kcat/Km) of MutH279K was
      enhanced by 2-fold as compared with the wild type (p<0.05). These results
      indicate that using protein modeling program and creating mutation, can enhance
      lipase activity and/or thermostability of SML and it also could be used for
      improving other properties of enzyme to the desired requirements as well as
      further mutations.

PMID- 27702478
TI  - Facile modulation of enantioselectivity of thermophilic Geobacillus zalihae
      lipase by regulating hydrophobicity of its Q114 oxyanion.
AB  - Site-directed mutagenesis of the oxyanion-containing amino acid Q114 in the
      recombinant thermophilic T1 lipase previously isolated from Geobacillus zalihae
      was performed to elucidate its role in the enzyme's enantioselectivity and
      reactivity. Substitution of Q114 with a hydrophobic methionine to yield mutant
      Q114M increased enantioselectivity (3.2-fold) and marginally improved reactivity
      (1.4-fold) of the lipase in catalysing esterification of ibuprofen with oleyl
      alcohol. The improved catalytic efficiency of Q114L was concomitant with reduced
      flexibility in the active site while the decreased enantioselectivity of Q114L
      could be directly attributed to diminished electrostatic repulsion of the
      substrate carboxylate ion that rendered partial loss in steric hindrance and thus
      enantioselectivity. The highest E-values for both Q114L (E-value 14.6) and Q114M
      (E-value 48.5) mutant lipases were attained at 50 degrees C, after 12-16h, with a
      molar ratio of oleyl alcohol to ibuprofen of 1.5:1 and at 2.0% (w/v) enzyme load
      without addition of molecular sieves. Pertinently, site-directed mutagenesis on
      the Q114 oxyanion of T1 resulted in improved enantioselectivity and such approach
      may be applicable to other lipases of the same family. We demonstrated that
      electrostatic repulsion phenomena could affect flexibility/rigidity of the enzyme
      substrate complex, aspects vital for enzyme activity and enantioselectivity of
      T1.

PMID- 27702480
TI  - A new strategy for strain improvement of Aurantiochytrium sp. based on heavy-ions
      mutagenesis and synergistic effects of cold stress and inhibitors of enoyl-ACP
      reductase.
AB  - Developing a strain with high docosahexaenoic acid (DHA) yield and stable
      fermenting-performance is an imperative way to improve DHA production using
      Aurantiochytrium sp., a microorganism with two fatty acid synthesis pathways:
      polyketide synthase (PKS) pathway and Type I fatty acid synthase (FAS) pathway.
      This study investigated the growth and metabolism response of Aurantiochytrium
      sp. CGMCC 6208 to two inhibitors of enoyl-ACP reductase of Type II FAS pathway
      (isoniazid and triclosan), and proposed a method of screening high DHA yield
      Aurantiochytrium sp. strains with heavy ion mutagenesis and pre-selection by
      synergistic usage of cold stress (4 degrees C) and FAS inhibitors (triclosan and
      isoniazid). Results showed that (1) isoniazid and triclosan have positive effects
      on improving DHA level of cells; (2) mutants from irradiation dosage of 120Gy
      yielded more DHA compared with cells from 40Gy, 80Gy treatment and wild type; (3)
      DHA contents of mutants pre-selected by inhibitors of enoyl-ACP reductase of Type
      II FAS pathway (isoniazid and triclosan)at 4 degrees C, were significantly higher
      than that of wild type; (4) compared to the wild type, the DHA productivity and
      yield of a mutant (T-99) obtained from Aurantiochytrium sp. CGMCC 6208 by the
      proposed method increased by 50% from 0.18 to 0.27g/Lh and 30% from 21 to 27g/L,
      respectively. In conclusion, this study developed a feasible method to screen
      Aurantiochytrium sp. with high DHA yield by a combination of heavy-ion
      mutagenesis and mutant-preselection by FAS inhibitors and cold stress.

PMID- 27702481
TI  - Biosynthesis of optically pure chiral alcohols by a substrate coupled and
      biphasic system with a short-chain dehydrogenase from Streptomyces griseus.
AB  - The increasing demand for biocatalysts in synthesizing enantiomerically pure
      chiral alcohols results from the outstanding characteristics of enzymes in
      reaction, economic, ecological issues. Many carbonyl reductases for producing
      chiral alcohols have been reported but there is still a lack of good catalytic
      efficacies. Herein, five carbonyl reductases from different Streptomyces were
      discovered by the strategy of genome mining. These reductases were overexpressed,
      and we chose SgCR for further study as it owned better enzyme activity. This
      protein was purified to apparent homogeneity, and its amino acid sequence was
      analyzed in comparison with that of the reported SDRs. The biocatalytic
      properties of SgCR were investigated, and this enzyme was confirmed to have the
      ability to convert various prochiral ketones into highly optically active
      alcohols. SgCR exhibited the highest activity towards ethyl 4-chloro-3
      oxobutanoate (COBE) and the corresponding product ethyl (S)-4-chloro-3
      hydroxybutanoate ((S)-CHBE) was obtained with high yield and excellent e.e. value
      by optimizing the biphasic system. Eventually, using isopropanol as the co
      substrate for NADH recycling in the substrate-coupled reaction, the yield and
      enantioselectivity of (S)-CHBE were obtained at the values of 90% and 99%,
      respectively. These results indicate that SgCR is a promising boicatalyst for the
      synthesis of chiral alcohols in industry.

PMID- 27702482
TI  - Unfolding of chondroitinase ABC Iota is dependent on thermodynamic driving force
      by kinetically rate constant-amplitude compensation: A stopped-flow fluorescence
      study.
AB  - We had previously investigated the role of a loop on the activity and
      conformational stability of chondroitinase ABC Iota (cABC Iota) by constructing
      some representative mutants in which a network interaction around Asp689 was
      manipulated. Here we extended our study by measuring the proteolytic resistance,
      long term and thermal stability as well as unfolding kinetics of these variants.
      Long term stability data at 4 and 25 degrees C for 3 weeks indicates that all
      mutants remain considerably active at 4 degrees C. Thermoinactivation rates for
      all variants shows that the wild type (WT) enzyme retained 50% of its activity
      after 2min keeping at 40 degrees C, while L701T, H700N and H700N/L701T as
      conformationally stabilized variants, have slower inactivation rate. It was also
      found that compact and thermodynamically stabilized variants are more resistant
      to tryptolytic digestion. Also, kinetic curves of chemical unfolding of the
      enzyme variants from stopped-flow fluorescence measurements were best fitted into
      a three-exponential function with three rate constants and corresponding
      amplitudes. We found that the energy barrier of the fast unfolding phase is lower
      in stabilized variants; while the amplitude of this phase to the whole amplitude
      of the unfolding reaction is lower than that of destabilized variants, indicating
      more population of stabilized mutants unfold via slower unfolding phase. We
      concluded that the rate of local conformational change alone is not the same that
      is expected from global thermodynamic stability; however the corresponding
      amplitude can compensate the rate constant toward thermodynamic stability.

PMID- 27702485
TI  - Metabolic pathway optimization for biosynthesis of 1,2,4-butanetriol from xylose
      by engineered Escherichia coli.
AB  - 1,2,4-Butanetriol (BT) and related derivatives have been widely used in many
      fields, especially in the military and in medicine. In this paper, we
      systematically optimized the BT biosynthetic pathway. We first investigated the
      activities of various NADH dependent aldehyde reductases (ALRs), which catalyze
      the fourth reaction in the four-step pathway for BT production from xylose in E.
      coli, and found that a combination of multiple endogenous enzymes catalyzed
      aldehyde reduction in the BT production bioprocess and that YqhD in E. coli was a
      main ALR for BT production. In addition, ADH2 from Saccharomyces cerevisiae can
      effectively catalyze 3,4-dihydroxybutanal to BT. Also, YjhG was identified as the
      major xylonate dehydratase and was co-overexpressed with YqhD, resulting in an
      improvement of BT production by 30%. Moreover, we identified and eliminated the
      competing branch pathway by inactivating 2-keto acid reductases (yiaE). Finally,
      the combination of these approaches led to BT production of 5.1g/L. In summary,
      our study provides insights into the biosynthetic pathway for BT production,
      demonstrates an effective strategy to enhance BT production, and paves the way
      toward in-depth research on BT biosynthesis.

PMID- 27702484
TI  - Effect of acid trehalase (ATH) on impaired yeast vacuolar activity.
AB  - In this study, this protein was overexpressed in yeast cells grown on trehalose
      containing medium to assess its impact on yeast vacuolar activity. ATH was
      confirmed to be located in both cell surface and vacuoles and the overexpression
      of ATH was observed to decrease vacuolar activity. Therefore, an assumption was
      suggested to explain this phenomenon as follows: when grown on containing
      trehalose medium, the ATH localization at cellular periplasm, but not the
      vacuole, is prioritized to utilize the extracellular trehalose for cell growth.
      The multivesicular body pathway (MVB pathway) via which ATH is transported into
      vacuoles is believed to be down-regulated to favor the accumulation of ATH at
      cell surface area. By extension, other vacuolar proteins travelling through MVB
      pathway to reach yeast vacuoles likely also suffer the down regulation. It can be
      concluded that acid trehalase may contribute down regulation of other vacuolar
      proteins through MVB pathway. This study suggests that it is a potential of acid
      trehalase (ATH) on impaired activity of yeast vacuolar.

PMID- 27702483
TI  - Matrix metalloproteinases as reagents for cell isolation.
AB  - Cell isolation methods for therapeutic purposes have seen little advancement over
      the years. The original methods of stem cell and islet isolation using bacterial
      collagenases were developed in the early 1980s and are still used today.
      Bacterial collagenases are subject to autodegradation, and isolates obtained with
      these enzymes may be contaminated with endotoxins, reducing cell viability and
      contributing to toxicity in downstream applications. Here we describe a novel
      method for isolation of mesenchymal stem cells from adipose tissue (ADSC)
      utilizing recombinantly produced matrix metalloproteases (MMPs). The ADSCs
      isolated by MMPs displayed essentially identical morphological and phenotypical
      characteristics to cells isolated by bacterially-derived collagenase I and
      LiberaseTM. Samples isolated with MMPs and LiberaseTM had comparable levels of
      CD73, CD90, and CD105. The adipogenic and osteogenic potential of the ADSCs
      isolated by MMPs was retained as compared to cells isolated with LiberaseTM.
      However, ADSCs isolated by LiberaseTM displayed 6% contamination with other cells
      as per negative markers revealed by PE staining, as opposed to<1% for all MMP
      treated samples. MMP-based cell isolation may contribute to optimization of
      transplantation technology.

PMID- 27702486
TI  - Effect of sulfonated lignin on enzymatic activity of the ligninolytic enzymes
      Calpha-dehydrogenase LigD and beta-etherase LigF.
AB  - NAD+-dependent Calpha-dehydrogenase LigD and glutathione-dependent beta-etherase
      LigF which selectively cleave the beta-O-4 aryl ether linkage present in lignin,
      are key-enzymes for the biocatalytic depolymerization of lignin. However, the
      catalytic efficiency of the two enzymes is low when they are used to break down
      the beta-aryl ether linkage in natural lignin. When sulfonated lignin was added
      to LigF hydrolysis reactions, the conversion rate of MPHPV decreased
      significantly from 99.5% to 32.6%. On the contrary, sulfonated lignin has little
      affection on LigD, which the conversion rate of GGE only decreased from 41.7% to
      41%. The strong nonspecific interactions of enzymes onto sulfonated lignin
      detected by surface plasmon resonance (SPR) and isothermal titration calorimetric
      (ITC) was obvious and universal, which can reduce enzyme activity of many
      enzymes, including ligninolytic enzyme beta-etherase LigF. To elucidate the exact
      mechanisms by which beta-etherase LigF interact with lignin, molecular modeling
      was applied. Finally, analysis on catalytic efficiency of LigD and LigF in
      different concentrations and molecular weights of sulfonated lignin, solution
      ionic strength, pH, temperature and concentration of Tween 80 revealed that
      electrostatic interactions and hydrophobic interactions play important roles in
      absorption between LigF and sulfonated lignin.

PMID- 27702487
TI  - Attenuating l-lysine production by deletion of ddh and lysE and their effect on l
      threonine and l-isoleucine production in Corynebacterium glutamicum.
AB  - The fermentative production of l-threonine and l-isoleucine with Corynebacterium
      glutamicum is usually accompanied by the by-production of l-lysine, which shares
      partial biosynthesis pathway with l-threonine and l-isoleucine. Since the direct
      precursor for l-lysine synthesis, diaminopimelate, is a component of
      peptidoglycan and thus essential for cell wall synthesis, reducing l-lysine by
      production could be troublesome. Here, a basal strain with eliminated l-lysine
      production was constructed from the wild type C. glutamicum ATCC13869 by deleting
      the chromosomal ddh and lysE. Furthermore, the basal strain as well as the ddh
      single mutant strain was engineered for l-threonine production by over-expressing
      lysC1, hom1 and thrB, and for l-isoleucine production by over-expressing lysC1,
      hom1, thrB and ilvA1. Fermentation experiments with the engineered strains showed
      that (i) deletion of ddh improved l-threonine production by 17%, and additional
      deletion of lysE further improved l-threonine production by 28%; (ii) deletion of
      ddh improved l-isoleucine production by 8% and improved cell growth by 21%,
      whereas additional deletion of lysE had no further influence on both l-isoleucine
      production and cell growth; (iii) l-lysine by-production was reduced by 95% and
      86% in l-threonine and l-isoleucine production, respectively, by deletion of ddh
      and lysE. This is the first report on improving l-threonine and l-isoleucine
      production by deleting ddh and lysE in C. glutamicum. The results demonstrate
      deletion of ddh and lysE as an effective strategy to reduce l-lysine by
      production without surrendering the cell growth of C. glutamicum.

PMID- 27702488
TI  - Phylogeny, classification and metagenomic bioprospecting of microbial acetyl
      xylan esterases.
AB  - Acetyl xylan esterases (AcXEs), also termed xylan deacetylases, are broad
      specificity Carbohydrate-Active Enzymes (CAZymes) that hydrolyse ester bonds to
      liberate acetic acid from acetylated hemicellulose (typically polymeric xylan and
      xylooligosaccharides). They belong to eight families within the Carbohydrate
      Esterase (CE) class of the CAZy database. AcXE classification is largely based on
      sequence-dependent phylogenetic relationships, supported in some instances with
      substrate specificity data. However, some sequence-based predictions of AcXE
      encoding gene identity have proved to be functionally incorrect. Such ambiguities
      can lead to mis-assignment of genes and enzymes during sequence data-mining,
      reinforcing the necessity for the experimental confirmation of the functional
      properties of putative AcXE-encoding gene products. Although one-third of all
      characterized CEs within CAZy families 1-7 and 16 are AcXEs, there is a need to
      expand the sequence database in order to strengthen the link between AcXE gene
      sequence and specificity. Currently, most AcXEs are derived from a limited range
      of (mostly microbial) sources and have been identified via culture-based
      bioprospecting methods, restricting current knowledge of AcXEs to data from
      relatively few microbial species. More recently, the successful identification of
      AcXEs via genome and metagenome mining has emphasised the huge potential of
      culture-independent bioprospecting strategies. We note, however, that the
      functional metagenomics approach is still hampered by screening bottlenecks. The
      most relevant recent reviews of AcXEs have focused primarily on the biochemical
      and functional properties of these enzymes. In this review, we focus on AcXE
      phylogeny, classification and the future of metagenomic bioprospecting for novel
      AcXEs.

PMID- 27702489
TI  - Utilizing intein-mediated protein cleaving for purification of uricase, a
      multimeric enzyme.
AB  - Uric acid, a side product of nucleotide metabolism, should be cleared from blood
      stream since its accumulation can cause cardiovascular diseases and gout. Uricase
      (urate oxidase) converts uric acid to 5-hydroxyisourate, but it is absent in
      human and other higher apes. Yet, the recombinant form of uricase, Rasburicase,
      is now commercially available to cure tumor lysis syndrome by lowering serum uric
      acid level. Developing new methods to efficiently purify pharmaceutical proteins
      like uricase has attracted researchers' attention. Self-cleaving intein mediated
      single column purification is one of these novel approaches. Self-cleaving
      inteins are modified forms of natural inteins that can excise and join only at
      one junction site. In this study, the synthetic gene of Aspergillus flavus
      uricase, a homotetrameric protein, was cloned into pTXB1 vector as a fusion with
      the N-terminal of Mxe GyrA intein and chitin-binding domain (CBD) for simple
      purification. Expression was confirmed by western blot analysis. The fusion
      protein containing uricase-intein-CBD was purified on a chitin column. The
      cleavage was induced by adding DTT,1 as a reducing agent to release uricase. The
      purity of uricase and complete excision of the intein and CBD were confirmed by
      SDS-PAGE2 while its proper folding was proved by circular dichroism and
      fluorescent emission studies. Isoelectric focusing further confirmed its
      homogeneity when a single protein band was observed at the predicted pI value.
      This is the first report of successful purification of a multimeric therapeutic
      enzyme by intein-mediated protein cleaving using a well-established and facile
      system.

PMID- 27702490
TI  - Genome mining and motif truncation of glycoside hydrolase family 5 endo-beta-1,4
      mannanase encoded by Aspergillus oryzae RIB40 for potential konjac flour
      hydrolysis or feed additive.
AB  - Two novel glycosyl hydrolase family 5 (GH5) beta-mannanases (AoMan5A and AoMan5B)
      were identified from Aspergillus oryzae RIB40 by genome mining. The AoMan5A
      contains a predicted family 1 carbohydrate binding module (CBM-1), located at its
      N-terminal. The AoMan5A, AoMan5B and truncated mutant AoMan5ADeltaCL (truncating
      the N-terminal CBM and linker of AoMan5A) were expressed retaining the N-terminus
      of the native protein in Pichia pastoris GS115 by pPIC9KM. The specific enzyme
      activity of the purified reAoMan5A, reAoMan5B and reAoMan5ADeltaCL towards locust
      bean gum at pH 3.6 and 40 degrees C for 10min, was 8.3, 104.2 and 15.8U/mg,
      respectively. The temperature properties of the reAoMan5ADeltaCL were improved by
      truncating CBM. They can degrade the pretreated konjac flour and produce
      prebiotics. In addition, they had excellent stability under simulative gastric
      fluid and simulative prilling process. All these properties make these
      recombinant beta-mannanases potential additives for use in the food and feed
      industries.

PMID- 27702491
TI  - Hyaluronic acid-supported combination of water insoluble immunostimulatory
      compounds for anti-cancer immunotherapy.
AB  - A novel powder-form combination adjuvant system containing two immunostimulatory
      compounds was firstly developed and evaluated as a therapeutic intervention for
      cancer immunotherapy. With the help of hyaluronic acid (HA), water insoluble
      monophosphoryl lipid A (MPL), QS21 and imiquimod (R837), could be easily
      dispersed in aqueous solution and lyophilized as powder-form, which have an
      advantage in room-temperature storage stability compared with those conventional
      liquid formulation that requires cold storage. Two kinds of HA-based combination
      vaccine adjuvants (HA/MPL/QS21, HMQ and HA/MPL/R837, HMR) contributed to the
      increase of both humoral and cellular immunity, which is very important for
      efficient cancer immunotherapy. Through the challenge experiments in EG7-OVA
      (mouse lymphoma-expressing OVA) tumor-bearing mice model, we found out that the
      immunostimulatory effects of HMQ and HMR were successful in the inhibition of
      tumor proliferation. Taken together, both HA-based powder-form combination
      adjuvant systems are expected to be used as potent prophylactic and therapeutic
      cancer vaccine.

PMID- 27702492
TI  - Hyaluronic acid conjugated micelles possessing CD44 targeting potential for gene
      delivery.
AB  - The high- and low-molecular weight hyaluronic acid (HHA and LHA) were used to
      conjugate with PLGA-PEG copolymers which were applied to encapsulate DOTAP/pDNA
      (D/P) lipoplex as a CD44-targeted micelle delivery system. The size and zeta
      potential of DNA loaded micelles were measured. The cytotoxicity and cellular
      transfection of DNA loaded micelles were performed in CD44-positive MDA-MB-231
      and MCF-7 cancer cells and CD44-negative HepG2 cells. The endocytosis mechanism
      of micelles was investigated further. The DNA loaded HA-conjugated micelles
      possessed negative-charged character which prevented erythrocytes from
      agglutination. Both LHA-PEG-PLGA and HHA-PEG-PLGA micelles had comparable
      cellular viability in L929 normal cells. The cellular transfection of HHA-PEG
      PLGA micelles was much higher than of LHA-PEG-PLGA micelles in CD44-positive
      cells. The specific and strong binding of HHA to CD44-positive cells resulted in
      the cellular transfection of HHA-PEG-PLGA micelles in CD44-positive cells
      significantly higher than in CD44-negative cells.

PMID- 27702493
TI  - Effects of concurrent ball milling and octenyl succinylation on structure and
      physicochemical properties of starch.
AB  - This work concerns the effects of concurrent ball milling (BM) and octenyl
      succinic anhydride (OSA) modification on the starch microstructure and
      physicochemical properties (swelling, emulsifying, and rheological). Unlike
      normal OSA-modified starches, the BM/OSA-modified starch displayed new features
      such as reduced viscosity and rigidity but increased paste stability during
      shearing, heating and cooling, regardless of the substitution degree. More
      interestingly, while the physicochemical properties could be regulated by simply
      altering the BM treatment time, BM/OSA was more efficient and effective at
      modulating starch properties during the initial period (approx. 10h), as seen by
      the rapid evolutions in starch structural disruption and OSA esterification.
      Thus, the BM/OSA modification can serve as a viable and cost-effective approach
      for producing octenyl succinate starches where low viscosity (at relatively high
      concentrations) and high paste stability are desired.

PMID- 27702494
TI  - Effect of low and high methoxyl citrus pectin on the properties of polypyrrole
      based electroactive hydrogels.
AB  - Electroactive hydrogels were prepared using commercial citric pectin, either raw
      (PC) or purified through dialysis (dPC), and chemically synthesized polypyrrole
      (PPy). 1H NMR analyses showed that PC is a low methoxyl pectin (degree of
      methoxylation, DM=46%) and dPC is a high methoxyl pectin (DM=77%). The pyrrole
      polymerization was monitored through UV-vis spectroscopy and both samples were
      observed to be good stabilizers for PPy in aqueous medium. The dispersions were
      used to prepare the hydrogels h-PC-PPy and h-dPC-PPy. The hydrogel h-dPC-PPy has
      a higher swelling index (SI~25%) at pH 1.2 than the hydrogel h-PC-PPy (SI~7%).
      Contrastingly, at pH 6.8 both hydrogels lost their mechanical integrity. Raman
      spectroscopy revealed that PPy is more oxidized in h-PC-PPy. Nevertheless, both
      hydrogels are electroactive and therefore can be considered for applications in
      which the control of the degree of swelling is desired.

PMID- 27702495
TI  - Functionalization of chitosan by a free radical reaction: Characterization,
      antioxidant and antibacterial potential.
AB  - Chitosan was functionalized with epigallocatechin gallate (EGCG) by a free
      radical-induced grafting procedure, which was carried out by a redox pair
      (ascorbic acid/hydrogen peroxide) as the radical initiator. The successful
      preparation of EGCG grafted-chitosan was verified by spectroscopic (UV, FTIR and
      XPS) and thermal (DSC and TGA) analyses. The degree of grafting of phenolic
      compounds onto the chitosan was determined by the Folin-Ciocalteu procedure.
      Additionally, the biological activities (antioxidant and antibacterial) of pure
      EGCG, blank chitosan and EGCG grafted-chitosan were evaluated. The spectroscopic
      and thermal results indicate chitosan functionalization with EGCG; the EGCG
      content was 25.8mg/g of EGCG grafted-chitosan. The antibacterial activity of the
      EGCG grafted-chitosan was increased compared to pure EGCG or blank chitosan
      against S. aureus and Pseudomonas sp. (p<0.05). Additionally, EGCG grafted
      chitosan showed higher antioxidant activity than blank chitosan. These results
      indicate that EGCG grafted-chitosan might be useful in active food packaging.

PMID- 27702496
TI  - Tribology of swollen starch granule suspensions from maize and potato.
AB  - The tribological properties of suspensions of cooked swollen starch granules are
      characterised for systems based on maize starch and potato starch. These systems
      are known as granule 'ghosts' due to the release (and removal) of polymer from
      their structure during cooking. Maize starch ghosts are less swollen than potato
      starch ghosts, resulting in a higher packing concentration and greater mechanical
      stability. In a soft-tribological contact, maize ghost suspensions reduce
      friction compared to the solvent (water), generate bell-shaped tribological
      profiles characteristic of particle entrainment and show a marked concentration
      dependence, whereas potato ghost suspensions exhibit lubrication behaviour
      similar to water. Microscopy analysis of the samples following tribological
      testing suggests that this is due to the rapid break-up of potato ghosts under
      the shear and rolling conditions within the tribological contact. A reduction in
      the small deformation moduli (associated with a weak gel structure) is also
      observed when the potato ghost suspensions are subjected to steady shear using
      parallel plate rheometry; both microscopy and particle size analysis show that
      this is accompanied by the partial shear-induced breakage of ghost particles.
      This interplay between particle microstructure and the resultant rheological and
      lubrication dynamics of starch ghost suspensions contributes to an enhanced
      mechanistic understanding of textural and other functional properties of cooked
      starches in food and other applications.

PMID- 27702497
TI  - Small-angle X-ray and light scattering analysis of multi-layered Curdlan gels
      prepared by a diffusion method.
AB  - Curdlan, a microbial polysaccharide, forms a multi-layered gel consisting of four
      layers with different turbidity when its alkaline solution is dialyzed against
      aqueous solutions containing Ca2+ (diffusion-set gel). The present study
      clarified the microstructure of each layer of the diffusion-set Curdlan gel by
      small-angle X-ray scattering (SAXS) and small-angle light scattering (SALS). The
      SAXS data showed that Curdlan chains assume a helical ordered conformation in the
      gel and that the gel consists of the fibrils formed by the association of Curdlan
      chains and the aggregates of fibrils. The SAXS results also indicated that the
      gelation is induced by the formation of a network of Ca2+-cross-linked fibrils in
      the outer region of the gel, whereas by the network formation of the aggregation
      of fibrils in the neutralization process in the inner region of the gel. A
      structural anisotropy of the gel was investigated by analysis of two-dimensional
      SAXS images, showing that the fibril is oriented circumferentially in the outer
      region of the cylindrical gel, whereas it is oriented randomly in the inner
      region of the gel. The SALS data showed that a characteristic length of an
      inhomogeneous structure in the turbid layers is of the order of micrometers. The
      observed spatial variation of the microscopic structure is caused by the
      difference in the paths of pH and [Ca2+] traced in the gelation process.

PMID- 27702498
TI  - Silk fibroin organization induced by chitosan in layer-by-layer films:
      Application as a matrix in a biosensor.
AB  - In this paper, we show that chitosan may induce conformation changes in silk
      fibroin (SF) in layer-by-layer (LbL) films, which were used as matrix for
      immobilization of the enzyme phytase to detect phytic acid. Three chitosan (CH)
      samples possessing distinct molecular weights were used to build CH/SF LbL films,
      and a larger change in conformation from random coils to beta-sheets for SF was
      observed for high molecular weight chitosan (CHH). The CHH/SF LbL films deposited
      onto interdigitated gold electrodes were coated with a layer of phytase, with
      which phytic acid could be detected down to 10-9M using impedance spectroscopy as
      the principle of detection and treating the data with a multidimensional
      projection technique. This high sensitivity may be ascribed to the suitability of
      the CHH/SF matrix, thus indicating that the molecular-level interactions between
      chitosan and SF may be exploited in other biosensors and biodevices.

PMID- 27702499
TI  - In situ functionalized nanobiocomposites dressings of bamboo cellulose
      nanocrystals and silver nanoparticles for accelerated wound healing.
AB  - An innovative approach was adopted where in situ synthesized silver nanoparticles
      (AgNPs) from leaf extract mediated reduction of AgNO3 were simultaneously
      impregnated into the matrix of cellulose nanocrystals (CNCs) isolated from
      Dendrocalamus hamiltonii and Bambusa bambos leaves, for formation of
      nanobiocomposites (NCs) in film and ointment forms. Here, use of plant CNCs was
      chosen as an alternate to bacterial cellulose for wound dressings. NCs possessing
      water absorption capacity and strong antibacterial activity showed synergistic
      effect on in vivo skin wound healing and documented faster and significant wound
      closure in treated mice. NCs exhibited lesser inflammation and early
      vasculogenesis at day 3 coupled with increased fibroblasts and collagen content
      at day 8 leading to faster neo-epithelization by day 14. Highly effective,
      biocompatible, and easy to apply NCs wound dressings (ointment and films)
      containing low amounts of Ag (0.05+/-0.01wt%) are potential candidates for
      effective skin repair.

PMID- 27702500
TI  - Effect of compression combined with steam treatment on the porosity, chemical
      compositon and cellulose crystalline structure of wood cell walls.
AB  - The changes of porosity, chemical composition and cellulose crystalline structure
      of Spruce (Picea abies Karst.) wood cell walls due to compression combined with
      steam treatment (CS-treatment) were investigated by nitrogen adsorption, confocal
      Raman microscopy (CRM) and X-ray diffraction (XRD), respectively. A number of
      slit-shaped mesopores with a diameter of 3.7nm was formed for the CS-treated
      wood, and more mesopores were found in the steam-treated wood. CRM results
      revealed cellulose structure was affected by treatment and beta-aryl-ether links
      associated to guaiacyl units of lignin was depolymerized followed by re
      condensation reactions. The crystallinity index (CrI) and crystallite thickness
      (D200) of cellulose for CS-treated wood were largely increased due to
      crystallization in the semicrystalline region. Higher degree of increase in both
      CrI and D200 was observed in both the earlywood and latewood of steam-treated
      wood, ascribing to the greater amount of mesopores in steam-treated wood than CS
      treated wood.

PMID- 27702501
TI  - Hydroxypropyl methylcellulose based aerogels: Synthesis, characterization and
      application as adsorbents for wastewater pollutants.
AB  - Hydroxypropyl methylcellulose (HPMC) E4M and J5MS samples with degrees of
      substitution of methyl groups (DS) 1.9 and 1.5, respectively, and molar
      substitutions of hydroxypropyl groups (MS) 0.25 and 0.75, respectively, were used
      to create aerogels in the presence of citric (cit), oxalic (oxa) or terephthalic
      (ter) acids, as crosslinkers. E4M-cit, J5MS-cit and J5MS-oxa aerogels presented
      outstanding stability in water, acid media, alcohols, acetone and hydrocarbons,
      density values of~(0.020+/-0.002)g/cm3, compressive modulus ranging from (111+/
      9)kPa to (133+/-11)kPa. On the other hand, E4M-oxa, E4M-ter and J5MS-ter aerogels
      were not adequate adsorbents because they collapsed in water. The adsorption
      behavior of 17alpha-ethinyl estradiol (EE) and methylene blue (MB) onto E4M-cit,
      J5MS-cit and J5MS-oxa aerogels were fitted to Freundlich model, indicating higher
      affinity of EE for J5MS-cit and J5MS-oxa and higher affinity of MB for E4M-cit
      aerogels. HPMC aeorogels could be successfully reused.

PMID- 27702502
TI  - In vitro release of metformin hydrochloride from sodium alginate/polyvinyl
      alcohol hydrogels.
AB  - Hydrogels, based on polysaccharides have found a number of applications as drug
      delivery carriers. In this work, hydrogels of full characterized sodium alginate
      (Mn 87,400g/mol) and commercial poly(vinyl alcohol) (PVA) sensitive to pH and
      temperature stimuli were obtained using a simple, controlled, green, low cost
      method based on freeze-thaw cycles. Stable hydrogels of sodium alginate/PVA with
      0.5:1.5 and 1.0:1.0w/v concentrations showed very good swelling ratio values in
      distilled water (14 and 20g/g, respectively). Encapsulation and release of
      metformin hydrochloride in hydrogels of 1.0:1.0w/v sodium alginate/PVA was
      followed by UV spectroscopy. The hydrogel released a very low amount of metformin
      hydrochloride at pH 1.2; the highest release value (55%) was obtained after 6h at
      pH 8.0. Also, the release of metformin hydrochloride was studied by 1H NMR
      spectroscopy, the temporal evolution of methyl group signals of metformin showed
      30% of drug release after 3h.

PMID- 27702503
TI  - Carbon disulfide-modified magnetic ion-imprinted chitosan-Fe(III): A novel
      adsorbent for simultaneous removal of tetracycline and cadmium.
AB  - A novel composite of carbon disulfide-modified magnetic ion-imprinted chitosan
      Fe(III), i.e., MMIC-Fe(III) composite, was prepared as an efficient adsorbent for
      the simultaneous removal of tetracycline (TC) and Cd(II). This adsorbent showed
      excellent performance in removing TC and Cd(II) due to its rapid kinetics, high
      adsorption capacity, good reusability, and was well suited for use with real
      water samples. Kinetics studies demonstrated that the adsorption proceeded
      according to a pseudo-second order model. The adsorption isotherms were well
      described by the Langmuir model, with maximum adsorption capacity for TC and
      Cd(II) being 516.29 and 194.31mg/g, respectively. The synergistic effect of TC
      and Cd(II) adsorption might be due to the formation of TC-Cd(II) complex bridging
      the adsorbate and adsorbent. These properties demonstrate the potential
      application of MMIC-Fe(III) for the simultaneous removal of TC and Cd(II), and
      may provide some information for the synergistic removal of antibiotics and heavy
      metals from aquatic environments.

PMID- 27702504
TI  - Integration of lysozyme into chitosan nanoparticles for improving antibacterial
      activity.
AB  - Lysozyme was integrated into chitosan nanoparticles (CS-NPs) to improve the
      antibacterial activity. CS-NPs and chitosan-lysozyme nanoparticles (CS-Lys-NPs)
      were prepared according to the ionic gelation technique and then characterized by
      average size, zeta potential, polydispersity index (PDI), atomic force microscopy
      (AFM), fourier transform infrared (FT-IR), small-angle X-ray scattering (SAXS),
      circular dichroism (CD) and UV-visible spectroscopy. Antibacterial properties
      were investigated by transmission electron microscopy (TEM) based on observation
      of the inhibition zone and measurement of the minimum inhibitory concentration
      (MIC) and minimum bacterial concentration (MBC) of CS-NPs and CS-Lys-NPs against
      E. coli and B. subtilis. The CS-NPs had particle sizes of 476.2-548.1nm, while an
      increase to ~488.8 to 613.5nm was observed upon loading with lysozyme. The
      results suggested that the integration of lysozyme into CS-NPs enhanced the
      antibacterial activity against E. coli and B. subtilis, which may show great
      potential for use in the food industry and other applications in the form of
      direct addition or incorporation into packaging.

PMID- 27702505
TI  - Preparation of chemically modified canola protein isolate with gum Arabic by
      means of Maillard reaction under wet-heating conditions.
AB  - The aim of this study was to produce covalently attached conjugate between canola
      protein isolate (CPI) and gum Arabic (GA) in aqueous solutions via the Maillard
      reaction at 90 degrees C in a model system consisting of 2% CPI and 1, 2 or 4%
      GA. Upon decreasing of free amino group content in the glycosylated CPI to 72%, a
      new band near the loading end of sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and a shift of CPI peak in high performance size exclusion
      chromatography confirmed that the covalent attachment of CPI to GA was
      successful. The results of secondary structure analysis suggested that grafted
      CPI had decreased alpha-helix and beta-sheet levels and increased random coils
      level. The solubility of CPI at isoelectric point was improved remarkably after
      grafting with GA. The optimal conjugation conditions chosen from the further
      experiments were 1% of GA, 90 degrees C and reaction time 15min.

PMID- 27702506
TI  - A novel pH-induced thermosensitive hydrogel composed of carboxymethyl chitosan
      and poloxamer cross-linked by glutaraldehyde for ophthalmic drug delivery.
AB  - In this work, a stimuli-responsive three dimensional cross-linked hydrogel system
      containing carboxymethyl chitosan (CMC) and poloxamer composed of a poly
      (ethylene oxide)/poly (propylene oxide)/poly (ethylene oxide) (PEO-PPO-PEO) block
      copolymer was constructed, and its aqueous solution was found to undergo a
      reversible sol-gel transition upon a temperature and/or pH change at a very low
      concentration. The hydrogels were synthesized via a cross-linking reaction using
      glutaraldehyde (GA) as the cross-linking agent. The structures of the hydrogels
      were characterized by FTIR, XRD, NMR and SEM studies and the swelling behaviour
      was studied in different buffered solutions. The results obtained indicated that
      cross-linked F127-CMC underwent discontinuous phase transition in different
      temperature and pH solutions. The hydrogels at 35 degrees C and pH 7.4 were found
      to have larger pores than at the other three conditions which resulted in greater
      swelling. The result of rheological studies showed that the gelation temperature
      was 32-33 degrees C and the viscosity of the hydrogel increased quickly after
      gelation. In an addition, the cytotoxicity and in vitro release was studied at
      different pH values and temperature. The results of a CCK-8 (Cell Counting Kit-8)
      assay showed that the hydrogel and its physical mixture solution were not
      cytotoxic to human corneal epithelial cells at a low concentration. Using the
      drug nepafenac (NP) as a model drug, the controlled drug release behaviour of
      these hydrogels was investigated. Owing to the formation of F127-CMC/NP retarding
      the diffusion rate of NP, a sustained release of NP from the hydrogel can be
      obtained. The release rate was found to be maximum at 35 degrees C and pH 7.4.
      From these preliminary evaluations, it is possible to conclude that the hydrogels
      have an excellent potential for application in ophthalmic drug delivery systems.

PMID- 27702507
TI  - Fabrication of aptamer decorated dextran coated nano-graphene oxide for targeted
      drug delivery.
AB  - In the current study, dextran (DEX) was covalently conjugated to the surface of
      nano-GO sheets, making stable biocompatible dextran coated GO (GO-DEX). The
      prepared GO-DEX was nontoxic to 4T1 mammary carcinoma cell line at concentrations
      up to 300MUg/mL. AS1411 aptamer, a ssDNA aptamer which can improve the
      intracellular uptake by nucleolin recognition, also has been introduced to
      hydroxyl groups of DEX in GO-DEX to produce GO-DEX-Apt. Moreover, curcumin (CUR),
      a natural polyphenol, found in the rhizomes of Curcuma longa (turmeric) which
      shows antineoplastic effects, was loaded onto the GO-DEX and GO-DEX-Apt via pi-pi
      stacking interactions with a high loading capacity (~29wt%). The GO-DEX-Apt-CUR
      could efficiently enter into 4T1 and MCF-7 nucleolin over-expressed cancer cells
      confirmed by fluorescence microscope and flowcytometry, and it also showed
      significantly higher cytotoxicity. These types of targeted nanoscale drug
      delivery vehicles on the basis of DEX coated GO may find potential application in
      cancer chemotherapy.

PMID- 27702508
TI  - Miscanthus Giganteus: A commercially viable sustainable source of cellulose
      nanocrystals.
AB  - With a goal of identifying a new scalable source for cellulose nanocrystals
      (CNCs), we successfully isolated CNCs from a sustainable, non-invasive grass,
      Miscanthus x. Giganteus (MxG). Subjecting MxG stalks to base hydrolysis,
      bleaching and acid hydrolysis allowed access to cellulose nanocrystals (MxG-CNC)
      in high yields. X-ray diffraction studies showed the crystallinity of the MxG
      CNCs increased with subsequent treatment conditions (>90% after HCl hydrolysis).
      Transmission electron microscopy showed that the MxG-CNC exhibit relatively high
      aspect ratios (60-70), and small angle neutron scattering showed the crystals
      were ribbon-like with a width and thickness of 8.5 and 2.8nm respectively. As
      expected, thermomechanical analysis of nanocomposites fabricated with carboxylic
      acid functionalized MxG-CNC (MxG-CNC-COOH) and PVAc showed an increase in modulus
      (above Tg) as filler content was increased. Comparing the properties to PVAc
      nanocomposites containing CNCs from wood showed at least as good, if not slightly
      better, reinforcement at the same loading level.

PMID- 27702509
TI  - Redox/pH dual stimuli-responsive degradable Salecan-g-SS-poly(IA-co-HEMA)
      hydrogel for release of doxorubicin.
AB  - Salecan is a novel water-soluble extracellular beta-glucan and possesses
      excellent physicochemical and biological properties. Here, redox/pH dual stimuli
      responsive hydrogel based on Salecan grafted with itaconic acid (IA) and 2
      hydroxyethyl methacrylate (HEMA) were prepared using disulfide-functionalized
      crosslinker N,N-bis(acryloyl)cystamine (BAC) for controlled drug delivery. The
      introduction of carboxylic groups endows the system with pH-sensitive character,
      swelling behavior of the hydrogel was conducted by changing the pH and Salecan
      content. It was demonstrated that DOX was efficiently loaded into the hydrogels
      and released in a controlled fashion via pH-control and swelling-shrinking
      mechanism. More importantly, DOX-loaded hydrogels showed dose dependent
      cytotoxicity toward A549 cell, and efficient cell killing was observed.
      Furthermore, a key point of this study was that the presence of disulfide linkage
      in system favored the degradation of hydrogels in the reductive environment.
      These results highlight the potential of Salecan-g-SS-poly(IA-co-HEMA) hydrogel
      as a novel system for the controlled release of anti-cancer drugs.

PMID- 27702510
TI  - The core structure of a Dendrobium huoshanense polysaccharide required for the
      inhibition of human lens epithelial cell apoptosis.
AB  - The aim of this work was to investigate the core structure of a Dendrobium
      huoshanense polysaccharide DHPD1 required for the inhibition of lens epithelial
      cell apoptosis. In order to obtain the fragments containing the core domain,
      pectinase was employed to hydrolyze DHPD1. After 24h reaction, it is interesting
      that the hydrolyzation seemed to be stopped, leading to a final enzymatic
      fragment DHPD1-24 with molecular weight about 1552Da. Compared to DHPD1, although
      the bioactivity is decreased, DHPD1-24 remained the ability to inhibit the H2O2
      induced apoptosis of human lens epithelial (HLE) cells via suppressing the MAPK
      signaling pathways. These results suggested that DHPD1-24 might be the core
      domain required for DHPD1 to inhibit HLE cell apoptosis. Methylation analysis
      showed DHPD1-24 was composed of (1->5)-linked-Araf, (1->3,6)-linked-Manp, 1
      linked-Glcp, (1->4)-linked-Glcp, (1->6)-linked-Glcp, (1->4,6)-linked-Glcp, (1->6)
      linked-Galp and 1-linked-Xylp in a molar ratio of
      1.06:1.53:2.11:2.04:0.93:0.91:0.36:1.01. Moreover, the primary structural
      features of DHPD1-24 were characterized by NMR spectrum.

PMID- 27702512
TI  - Relationships between protein content, starch molecular structure and grain size
      in barley.
AB  - Correlations among barley protein, starch molecular structure and grain size were
      determined using 30 barley samples with variable protein contents. Starch
      molecular structure was characterized by fluorophore-assisted carbohydrate
      electrophoresis and by size-exclusion chromatography (SEC, also termed GPC). The
      chain-length distributions of amylopectin were fitted using a mathematical model
      reflecting the relative activities of starch branching enzymes and starch
      synthase enzymes. Increased protein content significantly and negatively
      correlated with higher amounts of amylose with longer chains (degree of
      polymerization, DP 1600-40000) while barley grain sizes positively associated
      with starch contents. Protein content also positively correlated with the
      proportion of longer chains of amylopectin (DP 34-100). These results showed that
      the enzyme activities of starch synthases change with protein content, leading to
      altered starch contents, structures and grain sizes. From this perspective,
      selecting for large grain size (or low protein content) does not necessarily
      relate to starch structure, although may suggest long chains of amylopectin.
      Measuring starch structure could give a good indication of process performance in
      human food, animal feed and brewing, as all these structural features contribute
      to significant functional properties.

PMID- 27702511
TI  - Fractionation, preliminary structural characterization and bioactivities of
      polysaccharides from Sargassum pallidum.
AB  - Sargassum pallidum polysaccharides were fractioned using a DEAE-Sepharose fast
      flow column and four polysaccharide fractions (SP-P1, SP-P2, PV-P3 and SP-P4)
      were obtained. Structural analyses indicated that SP-P2 and SP-P4 had higher
      molecular weights than SP-P1 and SP-P3. SP-P2, SP-P3 and SP-P4 comprised of
      fucose, rhamnose, arabinose, galactose, glucose, xylose, and mannose in a similar
      molar ratio, while SP-P1 did not contain arabinose. SP-P2 and SP-P4 had a similar
      number of (1->6) or (1->) glycosidic linkages (1->2) or (1->4) glycosidic
      linkages and (1->3) glycosidic linkages, while SP-P1 and SP-P3 contained a small
      number of (1->3) glycosidic linkages. SP-P2 exhibited better bioactivities than
      SP-P1, SP-P3 and SP-P4, including antioxidant, anti-hemolysis inhibitory, alpha
      amylase and alpha-glucosidase inhibitory and antiproliferative activities. These
      data suggest that S. pallidum has four polysaccharide fractions with different
      structural features and bioactivities and SP-P2 has potential to be explored as a
      functional food or complementary medicine.

PMID- 27702513
TI  - Novel reverse osmosis membranes composed of modified PVA/Gum Arabic conjugates:
      Biofouling mitigation and chlorine resistance enhancement.
AB  - A novel crosslinked Poly (vinyl alcohol) (PVA) reverse osmosis (RO) thin film
      membrane conjugated with Gum Arabic (GA) with superb performance and features was
      synthesized for water desalination. RO membrane desalination parameters, such as
      hydrophilicity, surface roughness, water permeability, salt rejection, Chlorine
      resistance and biofouling resistance were evaluated using a dead end RO
      filtration unit. The incorporation of Pluronic F127 and the conjugation of Gum
      Arabic improved the overall RO performance of the membranes. This study has shown
      that the membrane PVA-GA-5 that contains 0.9wt% Gum Arabic provided excellent
      permeation, salt rejection, Chlorine and biofouling resistance and mechanical
      strength. The most remarkable result to arise from this research is that the
      overall RO performance enhancement has been achieved while utilizing PVA/Gum
      Arabic as a separation layer without the use of a substrate, which eliminates
      negative effects associated with the use of a substrate like internal
      concentration polarization.

PMID- 27702514
TI  - Alyssum homolocarpum seed gum-polyvinyl alcohol biodegradable composite film:
      Physicochemical, mechanical, thermal and barrier properties.
AB  - Films made from Alyssum homolocarpum seeds gum (AHSG) have poor mechanical and
      barrier (to oxygen) properties. In the present study poly vinyl alcohol (PVA) was
      used to improve the physicochemical properties of AHSG films. Results indicated
      that the addition of PVA significantly increased the moisture content,
      solubility, elongation at break (EB) and transparency while it decreased the
      density, oxygen permeability, chroma, water contact angle and Young modulus of
      AHSG based films. Films with higher AHSG to PVA ratios had lower water vapor
      permeability (WVP). The light barrier measurements presented low values of
      transparency at 600nm for PVA/AHSG films, indicating that films were very
      transparent while they had excellent barrier properties against UV light. Results
      for FTIR, DSC and SEM showed a clear interaction between PVA and AHSG, forming a
      new material. These results indicated that PVA/AHSG blend films had good
      compatibility.

PMID- 27702515
TI  - Novel hydrophobic cotton fibers adsorbent for the removal of nitrobenzene in
      aqueous solution.
AB  - In order to improve the superhydrophobic and oil-wet properties of raw cotton
      fibers come from Jiangsu province, China. A novel adsorbent, hydrophobic cotton
      fibers (HCF) with an excellent superhydrophobic and larger length was synthesized
      via modified sol-gel method and examined for the removal of nitrobenzene in
      aqueous solution. Results show that the treated raw cotton fibers exhibited
      outstanding non-wettability with the WCA of 152 degrees  and the larger length of
      0.2-0.4cm, which offers an opportunity to separation in for the removal of
      nitrobenzene. It was found that adsorption isotherm and kinetics of nitrobenzene
      onto HCF were well described by the Freundlich and pseudo-second-order kinetic
      models, respectively. The thermodynamic data showed that the nitrobenzene
      adsorption onto HCF was a spontaneous, endothermic and physisorption reaction.
      The monolayer adsorption capacity of nitrobenzene was found to be 16.85mg/g at 30
      degrees C.

PMID- 27702516
TI  - Radiation grafting of N-vinylcaprolactam onto nano and macrogels of chitosan:
      Synthesis and characterization.
AB  - The aim of this study was to synthesize chitosan hydrogels, in macro- and nano
      size, grafted with N-vinylcaprolactam (NVCL) using gamma radiation, and evaluate
      their potential application as a drug delivery system, using 5-fluorouracil (5
      FU) as a model drug. The effect of dose and monomer concentration in the grafting
      process was studied, and the materials were characterized by FTIR, TGA, DLS, SEM
      and AFM. Higher grafting percentages were observed for the nanogels system.
      Although both the grafted macro- and nanogels, (net-CS)-g-NVCL, showed a response
      to pH (4.75) and temperature (31-33 degrees C), the nanogels showed a better
      swelling response to both stimuli because of their higher surface area. Both
      systems were able to load 5-FU in small amounts (2-3.5mgg-1) and the release was
      sustained for more than 12h, showing that the modified macro and nanogels can be
      a potential alternative for the administration of drugs.

PMID- 27702517
TI  - The heparin-like activities of negatively charged derivatives of low-molecular
      weight polymannuronate and polyguluronate.
AB  - A series of low-molecular-weight polymannuronate (LPM) and polyguluronate (LPG)
      polyanionic derivatives, including LPM/LPG phosphate (LPMP/LPGP), LPM/LPG H
      phosphonate (LPMHP/LPGHP) and LPM/LPG sulfate (LPMS/LPGS), were prepared as
      heparinoids by chemical modification of LPM and LPG. The structures and
      characteristics of LPM, LPG and their derivatives were elucidated based on high
      performance gel permeation chromatography (HPGPC), fourier transform infrared
      spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR) and
      polyacrylamide gel electrophoresis (PAGE). In order to test the heparin-like
      activities of these derivatives and to reveal the activities affected by
      substituent groups and PM/PG polysaccharide backbones, the anticoagulant
      activities and FGF/FGFR1c signaling activation abilities were evaluated in vitro.
      The results showed that sulfate group was the best substituent group to improve
      the heparin-like activities of LPM/LPG compared with the other two anionic
      groups. The results also showed that sulfated derivative based on PG structure
      had better activities than that based on PM structure.

PMID- 27702518
TI  - Synthesis, characterization, and antimicrobial activities of sulfonated chitosan.
AB  - Sulfonated chitosan (SCS) was prepared via a facile chemical procedure by using
      1,3-propane sultone attached to the backbone of chitosan. The resulting chitosan
      derivative was characterized by Fourier transform-infrared spectroscopy, nuclear
      magnetic resonance spectroscopy, gel permeation chromatography, elemental
      analysis, and thermo gravimetric analysis. The antibacterial experiments
      demonstrated that SCS exhibited higher antibacterial activities against
      Escherichia coli and Staphylococcus aureus with the minimum inhibitory
      concentration (MIC) of 0.13mg/mL and 2.00mg/mL than those of water-soluble
      chitosan (WCS) with MIC of 0.50mg/mL and 4.00mg/mL. However, different antifungal
      activities of SCS against Arthrinium sacchari (MIC, 64.00mg/mL) and Botrytis
      cinerea (MIC, 0.25mg/mL) were observed. Scanning electron microscopy revealed
      that WCS and SCS could damage and deform the structure of fungal hyphae with
      different action modes. It is worth mentioning that SCS exhibited selective
      antifungal activity, which was an important parameter to control its biological
      performance in many fields.

PMID- 27702519
TI  - An improved pH-responsive carrier based on EDTA-Ca-alginate for oral delivery of
      Lactobacillus rhamnosus ATCC 53103.
AB  - A pH-responsive carrier based on an ethylenediaminetetraacetic-calcium-alginate
      (EDTA-Ca-Alg) system was developed by controlling the release of Ca2+. The system
      remained in the solution state at neutral pH since EDTA completely chelated the
      Ca2+. In contrast, a hydrogel immediately formed when the pH was below 4.0, which
      triggered the in situ release of Ca2+ from the EDTA-Ca compound and led to
      alginate-Ca binding. Taking advantage of the pH sensitivity, we prepared hydrogel
      microspheres with uniform size to entrap Lactobacillus rhamnosus ATCC 53103
      through emulsification. In an acidic environment, the hydrogel structure remained
      compact with negligible pores to protect L. rhamnosus ATCC 53103. However, in a
      neutral intestinal environment, the hydrogel structure gradually disassembled
      because of the Ca2+ release from the hydrogel, which caused cell release.
      Therefore, a pH-responsive carrier was developed for the protection and the
      controlled release of cells in gastrointestinal tract, thus providing potential
      for oral delivery of probiotics.

PMID- 27702520
TI  - Interface modified polylactic acid/starch/poly epsilon-caprolactone antibacterial
      nanocomposite blends for medical applications.
AB  - In this study, an optimized interface-modified ternary blend with antibacterial
      activity based on polylactic acid/starch/poly epsilon-caprolactone (PLASCL20),
      mixed with nano hydroxyapatite (nHA) via melt blending. This method results in a
      homogeneous nanocomposite blend in which the addition of 3% nHA improves the
      overall properties such as hydrolytic degradation, hydrophilicity, antibacterial
      activity and the drug release comparing to PLASCL20. Moreover, the simultaneous
      use of nHA and encapsulated triclosan (LATC30) compensated the negative effect of
      triclosan through increasing the possible cell attachment. According to the
      contact angle results, nHA was thermodynamically driven into the interface of PLA
      and PCL/Starch phases. The addition of 3% nHA showed a good adjustment between
      the hydrolytic degradation and the release profile, therefore, their electrospun
      microfibers demonstrated an improved fibroblast (L929) cell attachment. The
      aforementioned nanocomposite blend is a suitable antibacterial candidate for many
      medical applications with minimum side effects due to the controlled release of
      triclosan.

PMID- 27702521
TI  - High performance agar/graphene oxide composite aerogel for methylene blue
      removal.
AB  - A novel three-dimensional (3D) agar/graphene oxide (AGO) composite aerogel was
      prepared by a vacuum freeze drying method. The AGO aerogel was tested for its
      adsorption capacity of methylene blue (MB) and was found to have a maximum
      adsorption capacity of 578mg/g, as determined from the Langmuir isotherm. The
      adsorption kinetic studies revealed that adsorption followed pseudo-second-order
      model. The thermodynamic parameters calculated from the Van't Hoff equation
      indicate that the adsorption was an endothermic and spontaneous process. The
      adsorption mechanism may be attributed to electrostatic interaction between MB
      and AGO aerogel. Furthermore, the AGO aerogel can easily be recycled with a
      dilute NaOH solution wash, retaining over 91% of the adsorption capacity after
      recycling three times.

PMID- 27702523
TI  - The effect of ionotropic gelation residence time on alginate cross-linking and
      properties.
AB  - The ability to engineer biocompatible polymers with controllable properties is
      highly desirable. One such approach is to cross-link carbohydrate polymers using
      ionotropic gelation (IG). Previous studies have investigated the effect of curing
      time on alginate cross-linking. Herein, we discuss a novel study detailing the
      effect of IG residence time (IGRT) on the cross-linking of alginate with calcium
      ions (Ca2+) along with water migration (syneresis) and their subsequent impact on
      the pharmaceutical properties of alginate particles. IGRT was shown to have a
      significant effect on particle size, porosity, density, mechanical strength and
      swelling of calcium alginate particles as well as drug release mechanism.
      Furthermore, we describe a novel application of electron dispersive spectroscopy
      (EDS), in conjunction with Fourier Transform- infra red (FT-IR) spectroscopy, to
      analyze and monitor the changes in Ca2+ concentration during cross-linking. A
      simple procedure to determine the concentration and distribution of the surface
      and internal Ca2+ involved in alginate cross-linking was successfully developed.

PMID- 27702522
TI  - Physicochemical properties and in vitro antioxidant activities of polysaccharide
      from Artocarpus heterophyllus Lam. pulp.
AB  - A water-soluble polysaccharide from Artocarpus heterophyllus Lam. (jackfruit)
      pulp (JFP-Ps) was purified and its physicochemical properties were investigated.
      The in vitro antioxidant activities of JFP-Ps was evaluated by measuring DPPH and
      OH radicals scavenging activities, as well as reducing power. The results showed
      that JFP-Ps contained 79.12% of total sugar, 5.83% of protein, 15.65% of uronic
      acid, and 15 kinds of amino acids with high levels of Asp, Glu, Val, Leu and Lys.
      JFP-Ps was mainly composed of Rha, Ara, Gal, Glc, Xyl and GalA, with an average
      molecular weight of 1668kDa. FT-IR results showed the bands at the range of 1200
      850cm-1 suggested the presence of carbohydrates in JFP-Ps. The results of
      antioxidant activities showed that JFP-Ps exhibited strong DPPH and OH radical
      scavenging activities, with a relatively lower reducing power, suggesting that
      JFP-Ps can be exploited as effective natural antioxidant applications in medical
      and food industries.

PMID- 27702524
TI  - Bio-inspired production of chitosan/chitin films from liquid crystalline
      suspensions.
AB  - Inspired by chitin based hierarchical structures observed in arthropods
      exoskeleton, this work reports the capturing of chitin nanowhiskers' chiral
      nematic order into a chitosan matrix. For this purpose, highly crystalline chitin
      nanowhiskers (CTNW) with spindle-like morphology and average aspect ratio of 24.9
      were produced by acid hydrolysis of chitin. CTNW were uniformly dispersed at
      different concentrations in aqueous suspensions. The suspensions liquid
      crystalline phase domain was determined by rheological measurements and polarized
      optical microscopy (POM). Chitosan (CS) was added to the CTNW isotropic, biphasic
      and anisotropic suspensions and the solvent was evaporated to allow films
      formation. The Films' morphologies as well as the mechanical properties were
      explored. A correlation between experimental results and a theoretical model, for
      layered matrix' structures with fibers acting as a reinforcement agent, was
      established. The results evidence the existence of two different layered
      structures, one formed by chitosan layers induced by the presence of chitin and
      another formed by chitin nanowhiskers layers. By playing on the ratio
      chitin/chitosan one layered structure or the other can be obtained allowing the
      tunning of materials' mechanical properties.

PMID- 27702525
TI  - Preparation and characterization of agar-based nanocomposite films reinforced
      with bimetallic (Ag-Cu) alloy nanoparticles.
AB  - Agar-based active nanocomposite films were prepared by incorporating silver
      copper (Ag-Cu) alloy nanoparticles (NPs) (0.5-4wt%) into glycerol plasticized
      agar solution. Thermo-mechanical, morphological, structural, and optical
      properties of the nanocomposite films were characterized by texture analyzer,
      differential scanning calorimetry (DSC), scanning electron microscope (SEM), X
      ray diffraction (XRD), Fourier transforms infrared (FTIR) spectroscopy, and
      surface color measurement. Tensile strength and the melting temperature of the
      film increased linearly with NPs loading concentration. Color, transparency and
      UV barrier properties of agar films were influenced by the reinforcement of Ag-Cu
      NPs. XRD analysis confirmed the crystalline structure of the Agar/Ag-Cu
      nanocomposite films, whereas the smoothness and the homogeneity of film surface
      strongly reduced as observed through the SEM. The nanocomposite films exhibited a
      profound antibacterial activity against both Gram-positive (Listeria
      monocytogenes) and Gram-negative (Salmonella enterica sv typhimurium) bacteria.
      Overall, the agar nanocomposite films could be used as packaging material for
      food preservation by controlling foodborne pathogens and spoilage bacteria.

PMID- 27702527
TI  - Sodium alginate-assisted exfoliation of MoS2 and its reinforcement in polymer
      nanocomposites.
AB  - In this work, molybdenum disulfide (MoS2) nanosheets were facilely prepared by
      direct exfoliation of MoS2 in aqueous media with the assistance of sodium
      alginate (SA). Transmission electron microscopy (TEM), X-ray diffraction (XRD)
      and Raman spectra results showed that the raw MoS2 was successfully exfoliated
      into few-layer MoS2 nanosheets (SA-MoS2). FTIR and thermal gravimetric analysis
      (TGA) investigations showed that the obtained MoS2 nanosheets were modified by SA
      after exfoliation and improved dispersion in water were achieved. The obtained SA
      MoS2 nanosheets were employed to reinforce the water-soluble polymer SA. No
      obvious macroscopic phase separation could be found from the SA/SA-MoS2 films.
      Dynamic mechanical analysis (DMA) results showed that almost 9 times enhancement
      for the storage modulus of SA was achieved with the incorporation of only 0.5wt%
      of SA-MoS2, and the thermal stability of SA was also found improved with the
      addition of SA-MoS2 according to the thermal gravimetric analysis TGA results.

PMID- 27702526
TI  - Palm olein-in-water Pickering emulsion stabilized by Fe3O4-cellulose nanocrystal
      nanocomposites and their responses to pH.
AB  - We studied the formation of palm olein-in-water (O/W) Pickering emulsion
      stabilized by Fe3O4-cellulose nanocrystals (MCNC) nanocomposites obtained by
      ultrasound assisted in-situ co-precipitation method. The synthesized MCNC
      nanocomposites successfully stabilized Pickering emulsion with dual responses.
      The magnetic tests revealed a direct-relation between attractability of MCNC
      stabilized Pickering emulsions and the emulsion droplet diameter. The Pickering
      emulsions were stable under pH ranging from 3 to 6. The stability substantially
      reduced around pH 8-10, and regained slowly when approaching pH 13. From
      microscopic and mastersizer analysis, monodisperse emulsion droplets were noticed
      at pH 3-6, and 13, while polydisperse emulsion were obtained at pH 8-12. The
      Pickering emulsions prepared at pH 6 are stable up to 14 days, while Pickering
      emulsions at pH 8 experienced coalescence. In this study, the dual stimuli
      responsive Pickering emulsion stabilized by MCNC may hold potentials for
      biomedical and drug delivery as new generation of smart nanotherapeutic carrier.

PMID- 27702528
TI  - In vitro antioxidant activities of an exopolysaccharide from a salt pan bacterium
      Halolactibacillus miurensis.
AB  - Exopolysaccharide (EPS) designated as HMEPS was isolated from Halolactibacillus
      miurensis and purified through gel filtration chromatography. EPS extracted from
      the supernatant yielded a 56.1% total carbohydrate content. The ash and moisture
      content were 12.1% and 1.5% respectively. Galactose and glucose were found as
      main monosaccharides of the HMEPS through HPLC analysis. FT-IR spectra of the
      HMEPS revealed its composition with hydroxyl, alkenes, amide and carboxyl as
      functional groups and aliphatic amine and alkynes at the fingerprint region. In
      vitro antioxidant activity was investigated against hydroxyl, DPPH, superoxide
      free radicals and the scavenging activity against all were found to be dose
      dependent proportionately. HMEPS showed higher reducing ability against
      superoxide radical and potency in chelating the ferrous ions. 10mg/ml of HMEPS
      was found equivalent to 2.7units of ascorbic acid through the total antioxidant
      assay. Phylogenetic relation of H. miurensis SEEN MKU3 (GenBank number KT803852)
      was plotted with MEGA 5.0.

PMID- 27702529
TI  - Cisplatin-crosslinked glutathione-sensitive micelles loaded with doxorubicin for
      combination and targeted therapy of tumors.
AB  - The delivery of combination chemotherapy by nanoscale platforms has been
      demonstrated to enhance cancer treatment in the clinic. Cisplatin (CDDP)
      crosslinked, glutathione-sensitive, tumor-targeting micelles based on
      carboxymethyl chitosan were designed for synergistic cisplatin-doxorubicin (DOX)
      combination chemotherapy. In our study, DOX was conjugated to carboxymethyl
      chitosan through a disulfide bond, which was structurally characterized by 1H
      NMR. The micelles formed by self-assembly were spherical, with the mean diameter
      of 274nm. The in vitro release studies revealed that the micelles were highly
      glutathione-sensitive. Cytotoxicity analysis demonstrated that the cisplatin
      crosslinked micelles loaded with DOX exhibited enhanced therapeutic efficacy
      compared with the DOX-loaded nanoparticles, free DOX, and free CDDP. Cellular
      uptake and intracellular release revealed that the cisplatin-crosslinked micelles
      loaded with DOX could efficiently deliver and release DOX into the cancer cells.
      These results clearly indicate that tumor-targeting and glutathione-sensitive
      micelles provide means for combination drug delivery in cancer treatment.

PMID- 27702530
TI  - Synthesis and thermal properties of paramylon mixed esters and optical,
      mechanical, and crystal properties of their hot-pressed films.
AB  - Acylation of paramylon, a storage polysaccharide of Euglena gracilis, using
      multiple acid anhydrides yielded thermoplastic paramylon mixed esters without
      significant depolymerization. DSC examination showed that the shorter the acyl
      chain, the higher both the melting and glass transition temperature of the ester.
      TG analyses revealed their higher thermostability with the 5% weight loss
      temperature of ~330 degrees C. Melt volume flow rate examination revealed that
      the longer the acyl chain, the higher the thermoplasticity of the ester and that
      the esters exhibited higher thermoplasticity than structurally analogous esters
      made from cellulose and curdlan. A notable feature of the thermoplastic paramylon
      mixed esters is the availability of hot-pressing as a means of molding them into
      a film. Light transmittance and XRD measurements revealed that these films were
      transparent and in the amorphous state. Tensile tests indicated that the films
      had adequate mechanical strength comparable to those of the cellulose and curdlan
      analogues.

PMID- 27702531
TI  - Bacterial cellulose nanocrystals produced under different hydrolysis conditions:
      Properties and morphological features.
AB  - Bacterial cellulose (BC) is a polymer with interesting physical properties owing
      to the regular and uniform structure of its nanofibers, which are formed by
      amorphous (disordered) and crystalline (ordered) regions. Through hydrolysis with
      strong acids, it is possible to transform BC into a stable suspension of
      cellulose nanocrystals, adding new functionality to the material. The aim of this
      work was to evaluate the effects of inorganic acids on the production of BC
      nanocrystals (BCNCs). Acid hydrolysis was performed using different H2SO4
      concentrations and reaction times, and combined hydrolysis with H2SO4 and HCl was
      also investigated. The obtained cellulose nanostructures were needle-like with
      lengths ranging between 622 and 1322nm, and diameters ranging between 33.7 and
      44.3nm. The nanocrystals had a crystallinity index higher than native BC, and all
      BCNC suspensions exhibited zeta potential moduli greater than 30mV, indicating
      good colloidal stability. The mixture of acids resulted in improved thermal
      stability without decreased crystallinity.

PMID- 27702532
TI  - Microwave-assisted synthesis and characterization of hydrophilically
      functionalized polygalacturonic acid.
AB  - Microwave-assisted synthesis of a new class of polymeric surfactants based on
      polygalacturonic acid (PGA) is presented. PGA is water-insoluble and not surface
      active under normal conditions. Single-step hydrophilic modification of PGA with
      taurine (2-aminoethane sulfonic acid) renders it surface-active. The modification
      can be carried out either using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
      (EDCl) as a coupling agent or using microwave irradiation without a catalyst.
      Microwave irradiation significantly shortens reaction times and eliminates the
      need for a coupling agent. In all cases, functionalization was confirmed using 1H
      NMR, FTIR spectroscopy and elemental analysis. PGA-SO3 exhibits surface-active
      properties comparable to commercial surfactants, Triton X-100 and sodium lauryl
      sulfate. Detailed cytotoxicity evaluation performed using human dermal fibroblast
      (HDF) and human leukemic (HL-60) cell lines indicate that PGA-SO3 is not toxic
      even at 20 fold higher concentrations. These polymeric surfactants synthesized
      from PGA with no demonstrable cytotoxicity have the potential for serving as
      'greener' alternatives to common petrochemical-based surfactants.

PMID- 27702533
TI  - Synthesis and characterization of regioselectively substituted curdlan hetero
      esters via an unexpected acyl migration.
AB  - Regioselectively substituted curdlan esters were synthesized by protecting the C6
      primary hydroxyl group with a triphenylmethyl group followed by the acylation of
      the secondary hydroxyl groups at C2 and C4. The subsequent detritylation of C6
      trityl group under acidic conditions revealed an unexpected acyl migration from
      C4 to C6. This unique acyl migration in curdlan was first observed, which haven't
      been reported in other polysaccharides such as cellulose. The rate of this
      migration was found to be dependent on the length of the acyl group, leading to
      the proposal of a new mechanism for this transformation. Based on these results,
      we synthesized 2,6-di-O-acetyl-4-O-propionyl-curdlan, which was fully
      characterized by 1H NMR, 13C NMR, COSY, HSQC and HMBC analyses. Thermogravimetric
      analysis and differential scanning calorimetry measurements revealed that the
      regioselective esterification to curdlan promoted its crystallization compared
      with randomly mixed ester derivatives.

PMID- 27702534
TI  - Combinatory approach of methacrylated alginate and acid monomers for concrete
      applications.
AB  - Polysaccharides, and especially alginate, can be useful for self-healing of
      cracks in concrete. Instead of weak electrostatic bonds present within calcium
      alginate, covalent bonds, by methacrylation of the polysaccharides, will result
      in mechanically stronger superabsorbent polymers (SAPs). These methacrylated
      alginate chains as backbone are combined with two acrylic monomers in a varying
      molar fraction. These SAPs show a moisture uptake capacity up to 110% their own
      weight at a relative humidity of 95%, with a negligible hysteresis. The swelling
      capacity increased (up to 246 times its own weight) with a decreasing acrylic
      acid/2 acrylamido-2-methylpropane sulfonic acid ratio. The SAPs also showed a
      thermal stability up to 200 degrees C. Interestingly, the SAP composed of
      alginate and acrylic acid exerted a very limited decrease in compressive strength
      (up to 7% with addition of 1wt% SAP) rendering this material interesting for the
      envisaged self-healing application.

PMID- 27702535
TI  - Fabrication of stable galactosylated alginate microcapsules via covalent coupling
      onto hydroxyl groups for hepatocytes applications.
AB  - Galactose moieties are covalently coupled with sodium alginate to enhance liver
      specific functions in microcapsules owing to the specific interaction between the
      galactose moieties and the asialoglycoprotein receptors (ASGPRs) of hepatocytes.
      In this study, galactosylated alginate (L-NH2-OH-alginate) based microcapsules
      with desirable stability and a suitable 3D microenvironment are designed and
      fabricated for primary hepatocyte applications. The designed L-NH2-OH-alginate is
      fabricated via the application of ethylenediamine grafted lactobionic acid (L
      NH2) onto the hydroxyl groups of sodium alginate so that the negatively charged
      carboxyl groups intact in L-NH2-OH-alginate can effectively bond with Ca2+ to
      form a stable three-dimensional gel network; a subsequent reaction with
      polycations forms a stable membrane of microcapsules. As a result, L-NH2-OH
      alginate based microcapsules exhibit an excellent mechanical stability. Moreover,
      with a higher degree of substitution in L-NH2-OH-alginate (DS 0.41), the
      hepatocytes entrapped in L-NH2-OH-alginate microcapsules exhibit better viability
      and well-maintained liver-specific functions.

PMID- 27702536
TI  - Natural killer cell-mediated cytotoxicity is increased by a type II
      arabinogalactan from Anoectochilus formosanus.
AB  - This study investigated the effects of a type II arabinogalactan from
      Anoectochilus formosanus (AGAF) on natural killer (NK) cell-mediated cytotoxicity
      and the possible underlying mechanisms. This study reported that sustained
      exposure to AGAF increased NK-92MI cell-mediated cytotoxicity in a time- and
      concentration-dependent manner, as characterized according to the cellular lactic
      dehydrogenase leakage from K562 leukemia cells. Additionally, antibody
      neutralization studies have reported that interferon (IFN)-gamma, but not
      perforin or tumor necrosis factor-alpha, released by NK-92MI NK cells is crucial
      in enhancing cytotoxicity through an autocrine loop. In this study, AGAF was
      further demonstrated to induce IFN-gamma expression, increasing the
      susceptibility to NK-92MI cell-mediated cytotoxicity through the toll-like
      receptor (TLR)-2, TLR4, extracellular signal-regulated kinase, p38 mitogen
      activated protein kinase, and nuclear factor-kappaB pathways. A pharmacological
      study revealed that Janus kinase 2/signal transducers and activators of the
      signal transducers and of transcription 3 signaling are involved in IFN-gamma
      induced NK cell-mediated cytotoxicity.

PMID- 27702537
TI  - Factors affecting microstructure, physicochemical and textural properties of a
      novel Gum tragacanth-PVA blend cryogel.
AB  - Gum tragacanth (GT) gels are usually formed by using chemical crosslinkers which
      cause safety concerns owing to their toxicity. This study introduces a novel and
      safe method for gelation of GT in the presence of small amounts of polyvinyl
      alcohol (PVA) followed by successive freeze-thaw (F-T) cycles. Gel formation was
      performed at two GT: PVA mixing ratios (1:1 and 3:1), four F-T consecutive cycles
      and two different thawing temperatures (25 and 5 degrees C). Gel fraction,
      syneresis as well as mechanical properties and microstructural characteristics of
      the resultant gels were then studied. Gel fraction and mechanical properties
      improved by increasing F-T cycles and decreasing thawing temperature. Gel
      fraction increased by increasing the number of F-T cycles and decreasing the
      thawing temperature. Syneresis increased by increasing F-T cycles at GT: PVA
      mixing ratio of 1:1; whilst it was diminished at GT: PVA mixing ratio of 3:1.
      Microstructural observations by SEM confirmed mechanical properties.

PMID- 27702538
TI  - Impact of degree of oxidation on the physicochemical properties of
      microcrystalline cellulose.
AB  - Microcrystalline cellulose, a major component of cell wall of plants, is one of
      the most abundant natural materials, but the poor solubility of cellulose limits
      its applications. Cellulose is a linear glucan with exclusive beta 1->4 linkage.
      Oxidation carried out with TEMPO-NaBr-NaClO system can selectively oxidize the C6
      of glucose residues in cellulose. This modification improves polysaccharide
      solubility and other physicochemical properties. In this work, the impact of
      degree of oxidation on solubility, degree of crystallization, thermostability,
      molecular weight and the structures of the resulting oligosaccharide products of
      selectively oxidized cellulose were investigated using x-ray diffraction,
      thermogravimetric analysis, gel permeation chromatography-multiple angle laser
      light scattering and ultrahigh performance liquid chromatography-electrospray
      quadrupole/time of flight-mass spectrometry, respectively. The physicochemical
      properties of selectively oxidized cellulose having different degrees of
      oxidation were carefully characterized providing a theoretical foundation for the
      more accurate selection of applications of oxidized celluloses.

PMID- 27702539
TI  - Monitoring the architecture of anionic kappa-carrageenan/cationic glycine betaine
      amide surfactant assemblies by dilution: A multiscale approach.
AB  - The interaction between glycine betaine-based cationic surfactant and algal
      polysaccharide kappa-carrageenan was studied by investigating the dilution effect
      of the surfactant/polymer assemblies driven by electrostatic interactions. Two
      aqueous solutions of cationic surfactant and kappa-carrageenan at two molar
      ratios (3.5 and 0.8) diluted with factors of 5 and 10 times, were tested by
      various analytical methods including a multiscale observation by Transmission
      Electron Microscopy (TEM) and Laser Scanning Confocal Microscopy (LSCM) to
      understand the solution behavior of surfactant and oppositely charged polymer at
      both nano- and micrometer scale. Raman spectroscopy as well as confocal Raman
      imaging were applied to give Supplementary information about the
      surfactant/polysaccharide interactions and the distribution of assemblies. These
      analyses confirmed the formation of singular hybrid surfactant/polymer nano-,
      microobjects and they revealed the influence of dilution on the nanostructures.
      These results give an insight of the mechanism of the dilution effect on
      surfactant/polymer assemblies that could be valuable in pharmaceutical
      formulations, food and cosmetics fields.

PMID- 27702540
TI  - Cellulose and hemicellulose recovery from oil palm empty fruit bunch (EFB) fibers
      and production of sugars from the fibers.
AB  - A sequential two-step treatment with peracetic acid (PA) and alkaline peroxide
      (AP) at mild temperatures (20-35 degrees C) removed more than 98% of the lignin
      from oil palm empty fruit bunch (EFB) fiber. For each kilogram of EFB fiber
      treated, 200-250g of a solids fraction and 120-170g of a precipitate fraction
      were recovered after the treatment. Subsequent enzymatic hydrolysis (45 degrees
      C, 72h) of the recovered solids (excluding the precipitate) resulted in a glucose
      yield of 629.8+/-0.5g per kg of the original dry EFB biomass. Enzymatic
      hydrolysis of untreated EFB yielded only 3.0+/-0.0g glucose per kg of dry EFB.
      Therefore, the PA-AP pretreatment enhanced glucose recovery from EFB by nearly
      210-fold. The total treatment time was 93h (a 9h PA treatment at 35 degrees C, a
      12h treatment with AP (20 degrees C, 4% NaOH), 72h of enzymatic hydrolysis).

PMID- 27702541
TI  - Cellulose-g-poly(d-lactide) nanohybrids induced significant low melt viscosity
      and fast crystallization of fully bio-based nanocomposites.
AB  - Comb-like nanocrystal cellulose graft poly (d-lactide) (PDLA), i.e., NCC-g-PDLA
      nanohybrids were synthesized and compounded with poly (l-lactide) (PLLA) and poly
      (hydroxyalkanoate)s (PHA) to make fully biobased nanocomposites. Surprisingly,
      the complex viscosity of the PLLA/PHA melts was reduced by more than one order of
      magnitudes, viz. from 4000 to 100Pas by incorporation of 2-4wt% of the NCC-g-PDLA
      nanohybrids. Meanwhile, the crystallization of the PLLA component was accelerated
      by the NCC-g-PDLA nanohybrids due to the strong interaction between PDLA and PLLA
      macromolecules. The significant reduction in melt viscosity associating with
      unique core-shell-like microstructures due to the synergetic effect of the NCC-g
      PDLA nanohybrids and the PHA would facilitate the preparation of complex-shaped
      biomass articles and fibers under low(er) pressure and temperatures, which is
      beyond pure academic interest.

PMID- 27702542
TI  - Self-assembled high-strength hydroxyapatite/graphene oxide/chitosan composite
      hydrogel for bone tissue engineering.
AB  - Graphene hydrogel has shown greatly potentials in bone tissue engineering
      recently, but it is relatively weak in the practical use. Here we report a facile
      method to synthesize high strength composite graphene hydrogel. Graphene oxide
      (GO), hydroxyapatite (HA) nanoparticles (NPs) and chitosan (CS) self-assemble
      into a 3-dimensional hydrogel with the assistance of crosslinking agent genipin
      (GNP) for CS and reducing agent sodium ascorbate (NaVC) for GO simultaneously.
      The dense and oriented microstructure of the resulted composite gel endows it
      with high mechanical strength, high fixing capacity of HA and high porosity.
      These properties together with the good biocompatibility make the ternary
      composite gel a promising material for bone tissue engineering. Such a
      simultaneous crosslinking and reduction strategy can also be applied to produce a
      variety of 3D graphene-polymer based nanocomposites for biomaterials, energy
      storage materials and adsorbent materials.

PMID- 27702543
TI  - Bioactive potential and structural chracterization of sulfated polysaccharide
      from seaweed (Gracilaria corticata).
AB  - The Sulfated polysaccharide was purified through anion-exchange and gel
      permeation column chromatography. The isolated sulfated polysaccharide from C.
      corticata contains 84% of carbohydrate, 0% of protein, 19.7% of ash and 29.4% of
      moisture was found. The carbon, hydrogen, nitrogen and sulfur content as 33.19%,
      5.91%, 7.21% and 3.75%. The molecular weight of sulfated polysaccharide was found
      to be 43kDa. The sugar was composed of (90.11%), glucose (5.47%), xylose (2.30%)
      and mannose (2.12%). The structural feature of sulfated polysachharide was
      studied through FT-IR and 1H NMR spectral analysis. Further the sulfated
      polysaccharide showed total antioxidant activity of 24.93%-75.21% at 50
      250MUg/ml, DPPH free radical scavenging activity of 23.12%-73.01% at 10
      160MUg/ml, ABTS scavenging activity of 15.8%-74.5% at 25-125MUg/ml hydroxyl
      radical scavenging activity 12.87-69.19% at 25-125MUg/ml and superoxide radical
      scavenging activity 28.10-78.11% at 50-250MUg/ml respectively. The sulfated
      polysaccharide has shown good antibacterial activity against human pathogen.

PMID- 27702544
TI  - Acylation of cellulose nanocrystals with acids/trifluoroacetic anhydride and
      properties of films from esters of CNCs.
AB  - To eliminate the effect of humidity on nanopapers from nanocellulose, esters of
      CNCs (ECNCs) were synthesized via acylation of cellulose nanocrystals (CNCs) with
      fatty acids and Trifluoroacetic anhydride (TFAA). The structure information of
      ECNCs was confirmed via FTIR, degree of substitution (DS) determination, and XRD,
      respectively. With the increase of DS, the ECNCs could be dissolved in
      dichloromethane, which provided a ready way for fabrication of ECNCs films via
      casting/evaporation method. The tensile property, transmittance, hydrophobicity,
      thermal property and oxygen permeability of films were tested with universal
      tensile tester, UV-vis spectrophotometer, Contact angle tester, Simultaneous
      thermal analyzer and Oxygen permeability tester, respectively. With the increase
      of DS, the contact angles of ECNCs increased, and the water uptake decreased. The
      enhancement of hydrophobicity promised the preservation of tensile parameters for
      films after water absorbing. The hydrophobicity, high transmittance, and high
      oxygen barrier property make films have potential application in packaging filed.

PMID- 27702545
TI  - Structure and chain conformation of a neutral polysaccharide from sclerotia of
      Polyporus umbellatus.
AB  - A water-soluble heteropolysaccharide (PUP60W-1) was purified from the hot water
      extract of sclerotia of P. umbellatus by chromatography with DEAE Sepharose Fast
      Flow and Sephacryl S200 High-Resolution. The primary structure of PUP60W-1 was
      elucidated by GC, GC-MS and NMR. PUP60W-1 was identified as a highly branched
      polysaccharide composed of fucose, glucose and galactose in a ratio of
      1.0:0.9:13.3. The main repeating unit was identified as alpha-(1->6)-d
      galactopyranan backbone with substitution of terminal alpha-galactopyranosyl
      residues at O-2 for two out of every three main chain galactose residues. Its
      chain conformation was studied by atom force microscopy and size exclusion
      chromatography coupled with multiple detectors. The results revealed that PUP60W
      1 had a molecular weight of 2.47*104Da with a polydispersity index of 1.04, and
      existed in water as compact sphere structures which could be disrupted into
      smaller spherical chain blocks after dispersion with sodium dodecyl sulfate.

PMID- 27702546
TI  - Plantago major seed mucilage: Optimization of extraction and some physicochemical
      and rheological aspects.
AB  - The effect of different extraction procedures on functional properties of
      mucilage extracted from Plantago major seed were investigated using response
      surface methodology. Extraction at 75 degrees C, using 1:60 water:seed ratio at
      pH 6.8 was the best condition for maximum yield (15.18%), emulsion stability
      (67.4%), foam stability (88.4%), solubility (97.36%) and water absorption
      capacity (39.74g/g) of mucilage. At this optimum point, PMSM had, on average
      82.85% carbohydrate, 76.79 mgGAE/gdry total phenol content, 97.8mgg-1 total
      flavonoid content and 915.54MUgml-1 antioxidant activity. The results indicated
      that PMSM had average molecular weight of 1.2*106Da. FTIR analysis demonstrated
      the presence of carboxyl, hydroxyl and methyl groups and glycoside bonds. The
      chain flexibility parameter, activation energy, zeta-potential and droplet size
      for PMSM were determined as 946.09, 0.78*107J/kgmol, 15.23mV (at neutral pH) and
      448.56nm, respectively. Intrinsic viscosity for PMSM in deionized water was
      14.24dlg-1.

PMID- 27702547
TI  - Nicotine stabilization in composite sodium alginate based wafers and films for
      nicotine replacement therapy.
AB  - Composite wafers and films comprising HPMC and sodium alginate (SA) were
      formulated for nicotine (NIC) replacement therapy via the buccal route. Magnesium
      aluminium silicate (MAS) was added in different concentration ratios (0.25, 0.5,
      0.75) to stabilize NIC and its effect on mechanical properties, internal and
      surface morphology, physical form, thermal properties, swelling, mucoadhesion,
      drug content and release behaviour of the formulations was investigated. MAS
      changed the physico-mechanical properties of the composite formulations causing a
      decrease in mechanical hardness, collapsed wafer pores, increased roughness of
      film surface, increase in crystallinity and decreased mucoadhesion of the wafers.
      However, MAS increased swelling in both films and wafers as well as interaction
      between NIC and SA, which increased drug-loading capacity. Further, MAS resulted
      in rapid and slow release of NIC from wafers and films respectively. The results
      suggest that the ideal formulation for the stabilization of NIC in the composite
      formulations was MAS 0.25.

PMID- 27702548
TI  - The effect of starch amylose content on the morphology and properties of melt
      processed butyl-etherified starch/poly[(butylene succinate)-co-adipate] blends.
AB  - In this study, butyl-etherified waxy and high amylose starches were melt
      processed with biodegradable poly[(butylene succinate)-co-adipate] (PBSA) to
      improve the long-term stability of the starch-based materials. Butyl
      etherification was believed to improve the compatibility of starch with PBSA
      matrix. Scanning electron microscopy results demonstrated that highly branched
      amylopectin structures in butyl-etherified starch have better chemical
      interaction with the PBSA matrix compared to linear amylose structures.
      Thermogravimetric analysis revealed that the thermal stability of the blends
      decreased with increasing starch loading for all starch types with varying
      amylose content; however, the nature of the starch controlled the mechanical
      properties of the blends. Furthermore, the differential scanning calorimetric and
      polarised optical microscopic results demonstrated that the degree of
      crystallinity of PBSA decreased with increasing loading of amylopectin content in
      starch. Therefore, this work reveals the possibility of improving the inherent
      properties of starch by blending with PBSA through careful selection of the
      amylose content in starch.

PMID- 27702549
TI  - Thioredoxin interacting protein mediates lipid-induced impairment of glucose
      uptake in skeletal muscle.
AB  - Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus
      (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of
      circulating FFA leads to intra-myocellular lipid accumulation that induces
      mitochondrial ROS generation and worsens IR. However, the molecular mechanisms
      behind are unclear. We identified thioredoxin interacting protein (TxNIP), which
      is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed
      upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led
      to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake.
      FFA-induced overexpression of TxNIP gene was mediated through the activation of
      its bona-fide trans activator, ChREBP. Further, Palmitate-induced impairment in
      AMPK-SIRT-1 pathway resulted in overexpression of ChREBP. While Fenofibrate,
      abrogated PA-induced TxNIP expression and ROS generation in skeletal muscle
      cells, Saroglitazar, a dual PPARalpha/gamma-agonist, not only inhibited PA
      induced TXNIP expression but also led to greater improvement in glucose uptake.
      Taken together, TxNIP appears to be an important factor in FFA-induced ROS
      generation and IR in skeletal muscle cells, which can be modulated for the
      management of this complex disorder.

PMID- 27702550
TI  - Modulation of cytotoxic responses by targeting CD160 prolongs skin graft survival
      across major histocompatibility class I barrier.
AB  - CD160 is a glycosylphosphatidylinositol-anchored protein of the immunoglobulin
      superfamily. It exhibits a pattern of expression coincident in humans and mice
      that is mainly restricted to cytotoxic cells and to all intestinal
      intraepithelial T lymphocytes. B- and T-lymphocyte attenuator (BTLA) and CD160
      interact with cysteine-rich domain 1 of the extracellular region of Herpesvirus
      entry mediator (HVEM). CD160 engagement by HVEM can deliver inhibitory signals to
      a small subset of human CD4 T cells and attenuate its proliferation and cytokine
      secretion, but can also costimulate natural killer cells or intraepithelial
      lymphocytes. In turn, CD160 and BTLA can also function as agonist ligands being
      capable of costimulating T cells through membrane HVEM. Based on the restricted
      pattern of CD160 expression in cytotoxic cells, we postulated that CD160 may
      represent a suitable target for immune intervention in the setting of
      transplantation to modulate allogeneic cytotoxic responses. We demonstrated that
      in vivo administration of anti-CD160 antibody in combination with anti-CD40 L
      antibody to limit CD4 T-cell help modulated cytotoxic responses in a major
      histocompatibility complex class I mismatched model of allogeneic skin graft
      transplantation (bm1 donor to C57BL/6 recipient) and significantly prolonged
      graft survival. The implementation of this strategy in transplantation may
      reinforce current immunosuppression protocols and contribute to a better control
      of CD8 T-cell responses.

PMID- 27702551
TI  - Are the SDGs leaving safer surgical systems behind?
AB  - The World Health Organisation (WHO) has set out its new aims for the post-2015
      global agenda in the form of the Sustainable Development Goals (SDGs).
      Discussions around the historically neglected role of emergency and essential
      surgical interventions in global health has attracted widespread attention with
      the help of well-timed, high-profile reports including the Lancet Commission for
      Global Surgery [1]. The case for promoting safe surgery is clear with evidence
      suggesting that at least two-thirds of the years of life lost globally will be
      attributed to surgical conditions by 2025 [1]. In 2010 alone, almost 17 million
      lives, and more than 70 million disability-adjusted life years (DALYs) were lost
      due to surgically treatable conditions [1]. A central component of the SDGs is
      its renewed focus on health as a human right in the form of Universal Health
      Coverage (UHC). However, there are doubts as to how nations will be able to keep
      the 'promise of leaving no-one behind' without explicit reference to global
      surgery within the SDG framework [2].

PMID- 27702552
TI  - The effect of culture medium and carrier on explant culture of human limbal
      epithelium: A comparison of ultrastructure, keratin profile and gene expression.
AB  - Patients with limbal stem cell deficiency (LSCD) often experience pain and
      photophobia due to recurrent epithelial defects and chronic inflammation of the
      cornea. Successfully restoring a healthy corneal surface in these patients by
      transplantation of ex vivo expanded human limbal epithelial cells (LECs) may
      alleviate these symptoms and significantly improve their quality of life. The
      clinical outcome of transplantation is known to be influenced by the quality of
      transplanted cells. Presently, several different protocols for cultivation and
      transplantation of LECs are in use. However, no consensus on an optimal protocol
      exists. The aim of this study was to examine the effect of culture medium and
      carrier on the morphology, staining of selected keratins and global gene
      expression in ex vivo cultured LECs. Limbal biopsies from cadaveric donors were
      cultured for three weeks on human amniotic membrane (HAM) or on tissue culture
      coated plastic (PL) in either a complex medium (COM), containing recombinant
      growth factors, hormones, cholera toxin and fetal bovine serum, or in medium
      supplemented only with human serum (HS). The expanded LECs were examined by light
      microscopy (LM), transmission electron microscopy (TEM), immunohistochemistry
      (IHC) for keratins K3, K7, K8, K12, K13, K14, K15 and K19, as well as microarray
      and qRT-PCR analysis. The cultured LECs exhibited similar morphology and keratin
      staining on LM, TEM and IHC examination, regardless of the culture condition. The
      epithelium was multilayered, with cuboidal basal cells and flattened superficial
      cells. Cells were attached to each other by desmosomes. Adhesion complexes were
      observed between basal cells and the underlying carrier in LECs cultured on HAM,
      but not in LECs cultured on PL. GeneChip Human Gene 2.0 ST microarray
      (Affymetrix) analysis revealed that 18,653 transcripts were >=2 fold up or
      downregulated (p <= 0.05). Cells cultured in the same medium (COM or HS) showed
      more similarities in gene expression than cells cultured on the same carrier (HAM
      or PL). When each condition was compared to HAM/COM, no statistical difference
      was found in the transcription level of the selected genes associated with
      keratin expression, stemness, proliferation, differentiation, apoptosis, corneal
      wound healing or autophagy. In conclusion, the results indicate that ex vivo
      cultures of LECs on HAM and PL, using culture media supplemented with COM or HS,
      yield tissues with similar morphology and keratin staining. The gene expression
      appears to be more similar in cells cultured in the same medium (COM or HS)
      compared to cells cultured on the same carrier (HAM or PL).

PMID- 27702553
TI  - Cytokine gene expression and pathology in mice experimentally infected with
      different isolates of Trypanosoma evansi.
AB  - Aim of the present study was to assess the cytokine gene expression in liver,
      kidney and spleen and histopathological changes in mice infected with buffalo and
      dog isolates of Trypanosoma evansi. Forty-four Swiss albino mice was divided into
      eleven groups of four mice each and injected subcutaneously with 1 * 105
      trypanosomes of buffalo and dog isolate to twenty mice each, four mice served as
      control. Mice were examined for clinical signs, blood smear for trypanosome
      counts. Blood for PCR, liver, kidney, spleen, heart, lung, testis and abdominal
      muscle for histopathology and liver, kidney, spleen for cytokine gene expression
      studies, were collected. Mice showed dullness, lethargy, hunched back, sluggish
      movements on D4 and D5 in buffalo and dog isolate, respectively. Parasite count
      in blood varied between the two isolates of T. evansi. By PCR, trypanosome DNA
      was detected on D1 and D2 for buffalo and dog isolate, respectively. Splenomegaly
      was observed in mice infected with buffalo isolate but not with dog isolate.
      Histopathological changes were observed in liver, kidney, spleen and heart of
      mice but no changes in testis and abdominal muscles. Blood vessels of liver,
      heart, lung showed presence of trypanosomes in mice infected with buffalo isolate
      but not for dog isolate. Cytokine gene expression of IL-2, IL-4, IL-6, IL-12, TNF
      alpha and IFN-gamma increased in liver, kidney and spleen in both these isolates.
      However, the buffalo isolate exhibited pronounced increase in cytokine gene
      expression when compare to dog isolate of T. evansi. Anti-inflammatory cytokine
      gene IL-10 showed 50-60 and 10-20 folds increment in buffalo and dog isolates,
      respectively. This is the first report of IL-4, IL-6, IL-10 and IL-12 cytokine
      changes in mice infected with T. evansi. A variation in pathogenicity between
      buffalo and dog isolates was recorded indicating buffalo isolate of T. evansi
      remained more pathogenic in mice.

PMID- 27702554
TI  - SLC52A2 [p.P141T] and SLC52A3 [p.N21S] causing Brown-Vialetto-Van Laere Syndrome
      in an Indian patient: First genetically proven case with mutations in two
      riboflavin transporters.
AB  - BACKGROUND: Brown-Vialetto-Van Laere Syndrome (BVVLS), a rare neurological
      disorder characterized by bulbar palsies and sensorineural deafness, is mainly
      associated with defective riboflavin transporters encoded by the SLC52A2 and
      SLC52A3 genes. METHODS: Here we present a 16-year-old BVVLS patient belonging to
      a five generation consanguineous family from Indian ethnicity with two homozygous
      missense mutations viz., c.421C>A [p.P141T] in SLC52A2 and c.62A>G [p.N21S] in
      SLC52A3. RESULTS: Functional characterization based on 3H-riboflavin uptake assay
      and live-cell confocal imaging revealed that the effect of mutation c.421C>A
      [p.P141T] identified in SLC52A2 had a slight reduction in riboflavin uptake; on
      the other hand, the c.62A>G [p.N21S] identified in SLC52A3 showed a drastic
      reduction in riboflavin uptake, which appeared to be due to impaired trafficking
      and membrane targeting of the hRFVT-3 protein. CONCLUSIONS: This is the first
      report presenting mutations in both riboflavin transporters hRFVT-2 and hRFVT-3
      in the same BVVLS patient. Also, c.62A>G [p.N21S] in SLC52A3 appears to
      contribute more to the disease phenotype in this patient than c.421C>A [p.P141T]
      in SLC52A2.

PMID- 27702555
TI  - What Adherence Measures Should Be Used in Trials of Home-Based Rehabilitation
      Interventions? A Systematic Review of the Validity, Reliability, and
      Acceptability of Measures.
AB  - OBJECTIVE: To systematically review methods for measuring adherence used in home
      based rehabilitation trials and to evaluate their validity, reliability, and
      acceptability. DATA SOURCES: In phase 1 we searched the CENTRAL database, NHS
      Economic Evaluation Database, and Health Technology Assessment Database (January
      2000 to April 2013) to identify adherence measures used in randomized controlled
      trials of allied health professional home-based rehabilitation interventions. In
      phase 2 we searched the databases of MEDLINE, Embase, CINAHL, Allied and
      Complementary Medicine Database, PsycINFO, CENTRAL, ProQuest Nursing and Allied
      Health, and Web of Science (inception to April 2015) for measurement property
      assessments for each measure. STUDY SELECTION: Studies assessing the validity,
      reliability, or acceptability of adherence measures. DATA EXTRACTION: Two
      reviewers independently extracted data on participant and measure
      characteristics, measurement properties evaluated, evaluation methods, and
      outcome statistics and assessed study quality using the COnsensus-based Standards
      for the selection of health Measurement INstruments checklist. DATA SYNTHESIS: In
      phase 1 we included 8 adherence measures (56 trials). In phase 2, from the 222
      measurement property assessments identified in 109 studies, 22 high-quality
      measurement property assessments were narratively synthesized. Low-quality
      studies were used as supporting data. StepWatch Activity Monitor validly and
      acceptably measured short-term step count adherence. The Problematic Experiences
      of Therapy Scale validly and reliably assessed adherence to vestibular
      rehabilitation exercises. Adherence diaries had moderately high validity and
      acceptability across limited populations. The Borg 6 to 20 scale, Bassett and
      Prapavessis scale, and Yamax CW series had insufficient validity. Low-quality
      evidence supported use of the Joint Protection Behaviour Assessment. Polar A1
      series heart monitors were considered acceptable by 1 study. CONCLUSIONS: Current
      rehabilitation adherence measures are limited. Some possess promising validity
      and acceptability for certain parameters of adherence, situations, and
      populations and should be used in these situations. Rigorous evaluation of
      adherence measures in a broader range of populations is needed.

PMID- 27702557
TI  - TIMPing Fate: Why Pancreatic Cancer Cells Sojourn in the Liver.

PMID- 27702556
TI  - Intermittent Hypoxia and Locomotor Training Enhances Dynamic but Not Standing
      Balance in Patients With Incomplete Spinal Cord Injury.
AB  - OBJECTIVE: To test the effect of combined intermittent hypoxia (IH) and body
      weight-supported treadmill training (BWSTT) on standing and dynamic balance in
      persons with incomplete spinal cord injury (iSCI). DESIGN: Randomized, triple
      blind, placebo-controlled study. SETTING: Rehabilitation medical centers.
      PARTICIPANTS: Study participants (N=35) with chronic iSCI with American Spinal
      Injury Association grades C and D (>1y postinjury) were randomly assigned to
      either IH plus BWSTT (n=18) or continued normoxia (placebo) plus BWSTT protocol
      (n=17). INTERVENTIONS: Participants received either IH (alternating 1.5min 9%
      inspired O2 with 1.5min 21% inspired O2, 15 cycles per day) or continued normoxia
      (21% O2) combined with 45 minutes of BWSTT for 5 consecutive days, followed by 3
      times per week IH or normoxia plus BWSTT, for 3 additional weeks. MAIN OUTCOME
      MEASURES: Standing balance (normalized jerk and root-mean-square [RMS]) and
      dynamic balance (turning duration, cadence in a turn, and turn-to-sit duration)
      were assessed before and after IH and normoxia protocol by means of instrumented
      sway and instrumented timed Up and Go test. RESULTS: There was no significant
      difference in standing balance between interventions for both normalized jerk and
      RMS instrumented sway components (both P>.05). There was a significantly faster
      cadence (P<.001), turning duration (P<.001), and turn-to-sit duration (P=.001) in
      subjects receiving IH plus BWSTT, compared with placebo. CONCLUSIONS: A 4-week
      protocol of IH combined with locomotor training improves dynamic, but not
      standing, balance in persons with iSCI.

PMID- 27702558
TI  - Understanding Postcolonoscopy Colorectal Cancers: The Next Frontier.

PMID- 27702559
TI  - The Concept of Immune Tolerance in Chronic Hepatitis B Virus Infection Is Alive
      and Well.

PMID- 27702560
TI  - "To Be or Not to Be": Immune Tolerance in Chronic Hepatitis B.

PMID- 27702561
TI  - Diagnosis and Management of Low-Grade Dysplasia in Barrett's Esophagus: Expert
      Review From the Clinical Practice Updates Committee of the American
      Gastroenterological Association.
AB  - The purpose of this clinical practice update expert review is to define the key
      principles in the diagnosis and management of low-grade dysplasia (LGD) in
      Barrett's esophagus patients. The best practices outlined in this review are
      based on relevant publications, including systematic reviews and expert opinion
      (when applicable). Practice Advice 1: The extent of Barrett's esophagus should be
      defined using a standardized grading system documenting the circumferential and
      maximal extent of the columnar lined esophagus (Prague classification) with a
      clear description of landmarks and visible lesions (nodularity, ulceration) when
      present. Practice Advice 2: Given the significant interobserver variability among
      pathologists, the diagnosis of Barrett's esophagus with LGD should be confirmed
      by an expert gastrointestinal pathologist (defined as a pathologist with a
      special interest in Barrett's esophagus-related neoplasia who is recognized as an
      expert in this field by his/her peers). Practice Advice 3: Expert pathologists
      should report audits of their diagnosed cases of LGD, such as the frequency of
      LGD diagnosed among surveillance patients and/or the difference in incidence of
      neoplastic progression among patients diagnosed with LGD vs nondysplastic
      Barrett's esophagus. Practice Advice 4: Patients in whom the diagnosis of LGD is
      downgraded to nondysplastic Barrett's esophagus should be managed as
      nondysplastic Barrett's esophagus. Practice Advice 5: In Barrett's esophagus
      patients with confirmed LGD (based on expert gastrointestinal pathology review),
      repeat upper endoscopy using high-definition/high-resolution white-light
      endoscopy should be performed under maximal acid suppression (twice daily dosing
      of proton pump inhibitor therapy) in 8-12 weeks. Practice Advice 6: Under ideal
      circumstances, surveillance biopsies should not be performed in the presence of
      active inflammation (erosive esophagitis, Los Angeles grade C and D).
      Pathologists should be informed if biopsies are obtained in the setting of
      erosive esophagitis and if pathology findings suggest LGD, or if no biopsies are
      obtained, surveillance biopsies should be repeated after the anti-reflux regimen
      has been further intensified. Practice Advice 7: Surveillance biopsies should be
      performed in a four-quadrant fashion every 1-2 cm with target biopsies obtained
      from visible lesions taken first. Practice Advice 8: Patients with a confirmed
      histologic diagnosis of LGD should be referred to an endoscopist with expertise
      in managing Barrett's esophagus-related neoplasia practicing at centers equipped
      with high-definition endoscopy and capable of performing endoscopic resection and
      ablation. Practice Advice 9: Endoscopic resection should be performed in
      Barrett's esophagus patients with LGD with endoscopically visible abnormalities
      (no matter how subtle) in order to accurately assess the grade of dysplasia.
      Practice Advice 10: In patients with confirmed Barrett's esophagus with LGD by
      expert GI pathology review that persists on a second endoscopy, despite
      intensification of acid-suppressive therapy, risks and benefits of management
      options of endoscopic eradication therapy (specifically adverse events associated
      with endoscopic resection and ablation), and ongoing surveillance should be
      discussed and documented. Practice Advice 11: Endoscopic eradication therapy
      should be considered in patients with confirmed and persistent LGD with the goal
      of achieving complete eradication of intestinal metaplasia. Practice Advice 12:
      Patients with LGD undergoing surveillance rather than endoscopic eradication
      therapy should undergo surveillance every 6 months times 2, then annually unless
      there is reversion to nondysplastic Barrett's esophagus. Biopsies should be
      obtained in 4-quadrants every 1-2 cm and of any visible lesions. Practice Advice
      13: In patients with Barrett's esophagus-related LGD undergoing ablative therapy,
      radiofrequency ablation should be used. Practice Advice 14: Patients completing
      endoscopic eradication therapy should be enrolled in an endoscopic surveillance
      program. Patients who have achieved complete eradication of intestinal metaplasia
      should undergo surveillance every year for 2 years and then every 3 years
      thereafter to detect recurrent intestinal metaplasia and dysplasia. Patients who
      have not achieved complete eradication of intestinal metaplasia should undergo
      surveillance every 6 months for 1 year after the last endoscopy, then annually
      for 2 years, then every 3 years thereafter. Practice Advice 15: Following
      endoscopic eradication therapy, the biopsy protocol of obtaining biopsies in 4
      quadrants every 2 cm throughout the length of the original Barrett's esophagus
      segment and any visible columnar mucosa is suggested. Practice Advice 16:
      Endoscopists performing endoscopic eradication therapy should report audits of
      their rates of complete eradication of dysplasia and intestinal metaplasia and
      adverse events in clinical practice.

PMID- 27702562
TI  - Hepatitis C Therapy: Game Over!

PMID- 27702563
TI  - Bioprospecting for secondary metabolites in the entomopathogenic bacterium
      Photorhabdus luminescens subsp. sonorensis.
AB  - Crude extracts of in vitro and in vivo cultures of two strains of Photorhabdus l.
      sonorensis (Enterobacteriaceae) were analyzed by TLC, HPLC-UV and LC-MS. Nine
      unique compounds with mass/charge ratios (m/z) ranging from 331.3 to 713.5 were
      found in MS analyses. Bioactivity of extracts was assessed on a selection of
      plant pathogens/pests and non-target species. Caborca strain extracts showed the
      highest activity against Helicoverpa zea (Lepidoptera: Noctuidae) neonates at all
      concentrations tested. Mortality ranged from 11% (at 10MUg/ml) to 37% (at
      40MUg/ml). Strain CH35 extracts showed the highest nematicidal activity on
      Meloidogyne incognita (Tylenchida: Meloidogynidae) at 40MUg/ml. Low to no
      nematicidal activity was observed against the non-target species Steinernema
      carpocapsae (Rhabditida: Steinernematidae) and Caenorhabditis elegans
      (Rhabditida: Rhabditidae). Caborca extracts exhibited a strong antibiotic effect
      on Pseudomonas syringae (Pseudomonadales: Pseudomonadacedae) at 40MUg/ml, while
      both Caborca and CH35 extracts inhibited the growth of Bacillus subitillis
      (Bacillales: Bacillaceae) at 40MUg/ml. All extracts strongly inhibited the growth
      of the fungus Fusarium oxysporum (Hypocreales: Nectriceae) but not that of
      Alternaria alternata (Pleosporales: Pleosporaceae). Contrastingly, a moderate to
      high inhibitory effect was denoted on the non-target biocontrol fungus Beauveria
      bassiana (Hypocreales: Clavivipitaceae).

PMID- 27702564
TI  - Testosterone and androgen receptor gene polymorphism are associated with
      confidence and competitiveness in men.
AB  - A contribution to a special issue on Hormones and Human Competition. Studies in
      non-human animals and humans have demonstrated the important role of testosterone
      in competitive interactions. Here, we investigated whether endogenous
      testosterone levels predict the decision to compete, in a design excluding spite
      as a motive underlying competitiveness. In a laboratory experiment with real
      monetary incentives, 181 men solved arithmetic problems, first under a
      noncompetitive piece rate, followed by a competition incentive scheme. We also
      assessed several parameters relevant to competition, such as risk taking,
      performance, and confidence in one's own performance. Salivary testosterone
      levels were measured before and 20min after the competition task using mass
      spectrometry. Participants were also genotyped for the CAG repeat polymorphism of
      the androgen receptor gene, known to influence the efficacy of testosterone
      signaling in a reciprocal relationship to the number of CAG repeats. We observed
      a significant positive association between basal testosterone levels and the
      decision to compete, and that higher testosterone levels were related to greater
      confidence in one's own performance. Whereas the number of CAG repeats was not
      associated with the choice to compete, a lower number of CAG repeats was related
      to greater confidence in those who chose to compete, but this effect was
      attributable to the polymorphism's effect on actual performance. An increase in
      testosterone levels was observed following the experiment, and this increase
      varied with self-reported high-school math grades. We expand upon the latest
      research by documenting effects of the androgen system in confidence in one's own
      ability, and conclude that testosterone promotes competitiveness without spite.

PMID- 27702566
TI  - Oxidative Damage Control in a Human (Mini-) Organ: Nrf2 Activation Protects
      against Oxidative Stress-Induced Hair Growth Inhibition.
AB  - The in situ control of redox insult in human organs is of major clinical
      relevance, yet remains incompletely understood. Activation of nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2), the "master regulator" of genes controlling
      cellular redox homeostasis, is advocated as a therapeutic strategy for diseases
      with severely impaired redox balance. It remains to be shown whether this
      strategy is effective in human organs, rather than only in isolated human cell
      types. We have therefore explored the role of Nrf2 in a uniquely accessible human
      (mini-) organ: scalp hair follicles. Microarray and qRT-PCR analysis of human
      hair follicles after Nrf2 activation using sulforaphane identified the modulation
      of phase II metabolism, reactive oxygen species clearance, the pentose phosphate
      pathway, and glutathione homeostasis. Nrf2 knockdown (small interfering RNA) in
      cultured human hair follicles confirmed the regulation of key Nrf2 target genes
      (i.e., heme oxygenase-1, NAD(P)H dehydrogenase, quinone 1, glutathione reductase,
      glutamate-cysteine ligase catalytic subunit, ABCC1, peroxiredoxin 1).
      Importantly, Nrf2 activation significantly reduced reactive oxygen species levels
      and associated lipid peroxidation. Nrf2 preactivation reduced premature catagen
      and hair growth inhibition induced by oxidative stress (H2O2 or menadione),
      significantly ameliorated the H2O2-dependent increase in matrix keratinocyte
      apoptosis and reversed the reactive oxygen species-induced reduction in hair
      matrix proliferation. This study thus provides direct evidence for the crucial
      role of Nrf2 in protecting human organ function (i.e., scalp hair follicles)
      against redox insult.

PMID- 27702567
TI  - Inhibition of M1 macrophage activation in adipose tissue by berberine improves
      insulin resistance.
AB  - AIMS: Insulin resistance is associated with a chronic inflammation in adipose
      tissue which is propagated by a phenotypic switch in adipose tissue macrophage
      (ATM) polarization. This study aimed to investigate whether berberine, the major
      alkaloid of rhizoma coptidis, can improve insulin resistance through inhibiting
      ATM activation and inflammatory response in adipose tissue. MAIN METHODS: High
      fat-diet induced obese mice were administered oral with berberine (50mg/kg/day)
      for 14days. ATMs were analysed using FACS and insulin resistance was evaluated.
      Expressions of pro-inflammatory cytokines and activation of inflammatory pathways
      were detected. The chemotaxis of macrophages was measured. Glucose consumption
      and insulin signalling of adipocytes were examined. KEY FINDINGS: Berberine
      significantly decreased F4/80+/CD11c+/CD206- cells in the stromal vascular
      fraction from adipose tissue and improved glucose tolerance in obsess mice. In
      addition, berberine reduced the elevated levels of serum TNF-alpha, IL-6 and MCP
      1 and the expressions of TNF-alpha, IL-6 and MCP-1 and attenuated the
      phosphorylation of JNK and IKKbeta and the expression of NF-kappaB p65 in the
      obese adipose tissue, Raw264.7 macrophages and 3T3-L1 adipocytes, respectively.
      The phosphorylation of IRS-1 (Ser307) was inhibited by berberine in adipose
      tissue and cultured adipocytes. The phosphorylation of AKT (Ser473) was increased
      in berberine-treated adipose tissue. Conditioned medium from adipocytes treated
      with berberine reduced the number of infiltrated macrophages. Berberine partly
      restored the impaired glucose consumption and the activation of IRS-1 (Ser307) in
      adipocytes induced by the activation of macrophages. SIGNIFICANCE: Our findings
      imply that berberine improves insulin resistance by inhibiting M1 macrophage
      activation in adipose tissue.

PMID- 27702565
TI  - IL-1beta-Induced Protection of Keratinocytes against Staphylococcus aureus
      Secreted Proteases Is Mediated by Human beta-Defensin 2.
AB  - Atopic dermatitis (AD) is a common chronic inflammatory skin disease that results
      in significant morbidity. A hallmark of AD is disruption of the critical barrier
      function of upper epidermal layers, causatively linked to environmental stimuli,
      genetics, and infection, and a critical current target for the development of new
      therapeutic and prophylactic interventions. Staphylococcus aureus is an AD
      associated pathogen producing virulence factors that induce skin barrier
      disruption in vivo and contribute to AD pathogenesis. We show, using immortalized
      and primary keratinocytes, that S. aureus protease SspA/V8 is the dominant
      secreted factor (in laboratory and AD clinical strains of S. aureus) inducing
      barrier integrity impairment and tight junction damage. V8-induced integrity
      damage was inhibited by an IL-1beta-mediated mechanism, independent of effects on
      claudin-1. Induction of keratinocyte expression of the antimicrobial/host defense
      peptide human beta-defensin 2 (hBD2) was found to be the mechanism underpinning
      this protective effect. Endogenous hBD2 expression was required and sufficient
      for protection against V8 protease-mediated integrity damage, and exogenous
      application of hBD2 was protective. This modulatory property of hBD2, unrelated
      to antibacterial effects, gives new significance to the defective induction of
      hBD2 in the barrier-defective skin lesions of AD and indicates therapeutic
      potential.

PMID- 27702570
TI  - Rapid tin-mediated access to a lysophosphatidylethanolamine (LPE) library:
      Application to positional LC/MS analysis for hepatic LPEs in non-alcoholic
      steatohepatitis model mice.
AB  - Even though lysophospholipids have attracted much interest in recent years on
      account of their unique bioactivity, research related to lysophospholipids is
      usually hampered by problems associated with standard sample preparation and
      discrimination of regioisomers. Herein, we demonstrate a quick tin-chemistry
      based synthetic route to lysophosphatidylethanolamines (LPEs) and its application
      in the positional analysis of hepatic LPEs in non-alcoholic steatohepatitis
      (NASH) model mice. We found that the preference of hepatic LPE regioisomer
      largely depends on the unsaturation of acyl chain in both control and NASH model
      mice. In addition, hepatic C18:2-LPE and C20:5-LPE levels were significantly
      lower in the NASH model mice than those in the control. The LC/MS technique based
      on the library of LPE regioisomers allows an accurate observation of hepatic LPE
      metabolism and might provide useful information to elucidate yet ambiguous
      pathogenesis of NASH.

PMID- 27702568
TI  - Endoscopist fatigue estimates and colonoscopic adenoma detection in a large
      community-based setting.
AB  - BACKGROUND AND AIMS: Endoscopist fatigue may impact colonoscopy quality, but
      prior studies conflict, and minimal data exist from community-based practices
      where most colonoscopies are performed. METHODS: Within a large, community-based
      integrated healthcare system, we evaluated the associations among 4 measures of
      endoscopist fatigue and colonoscopic adenoma detection from 2010 to 2013. Fatigue
      measures included afternoon versus morning colonoscopy and the number of GI
      procedures performed before a given colonoscopy, including consideration of prior
      procedure complexity. Analyses were adjusted for potential confounders using
      multivariate logistic regression. RESULTS: We identified 126 gastroenterologists
      who performed 259,064 total GI procedures (median, 6 per day; range, 1-24),
      including 76,445 screening and surveillance colonoscopies. Compared with morning
      examinations, colonoscopies in the afternoon were not associated with lower
      adenoma detection for screening examinations, surveillance examinations, or their
      combination (OR for combination, .99; 95% CI, .96-1.03). The number of procedures
      performed before a given colonoscopy, with or without consideration of prior
      procedure complexity, was also not inversely associated with adenoma detection
      (OR for adenoma detection for colonoscopies in the fourth quartile of fatigue
      based on the number of prior procedures performed vs colonoscopies performed as
      the first procedure of the day, .99; 95% CI, .94-1.04). CONCLUSIONS: In a large
      community-based setting, adenoma detection for screening and surveillance
      colonoscopies were not associated with either time of day or the number of prior
      procedures performed by the endoscopist, within the range of procedure volumes
      evaluated. The lack of association persisted after accounting for prior procedure
      complexity.

PMID- 27702571
TI  - The Challenges of Teaching Ambulatory Internal Medicine: Faculty Recruitment,
      Retention, and Development: An AAIM/SGIM Position Paper.

PMID- 27702572
TI  - Acute high-intensity noise induces rapid Arc protein expression but fails to
      rapidly change GAD expression in amygdala and hippocampus of rats: Effects of
      treatment with D-cycloserine.
AB  - Tinnitus is a devastating auditory disorder impacting a growing number of people
      each year. The aims of the current experiment were to assess neuronal mechanisms
      involved in the initial plasticity after traumatic noise exposure that could
      contribute to the emergence of tinnitus and to test a potential pharmacological
      treatment to alter this early neural plasticity. Specifically, this study
      addressed rapid effects of acute noise trauma on amygdalo-hippocampal circuitry,
      characterizing biomarkers of both excitation and inhibition in these limbic
      regions, and compared them to expression of these same markers in primary
      auditory cortex shortly after acute noise trauma. To assess excitatory
      plasticity, activity-regulated cytoskeleton-associated (Arc) protein expression
      was evaluated in male rats 45 min after bilateral exposure to acute high
      intensity noise (16 kHz, 115 dB SPL, for 1 h), sufficient to cause acute cochlear
      trauma, a common cause of tinnitus in humans and previously shown sufficient to
      induce tinnitus in rat models of this auditory neuropathology. Western blot
      analyses confirmed that up-regulation of amygdalo-hippocampal Arc expression
      occurred rapidly post-noise trauma, corroborating several lines of evidence from
      our own and other laboratories indicating that limbic brain structures, i.e.
      outside of the classical auditory pathways, exhibit plasticity early in the
      initiation of tinnitus. Western blot analyses revealed no noise-induced changes
      in amygdalo-hippocampal expression of glutamate decarboxylase (GAD), the
      biosynthetic enzyme required for GABAergic inhibition. No changes in either Arc
      or GAD protein expression were observed in primary auditory cortex in this
      immediate post-noise exposure period, confirming other reports that auditory
      cortical plasticity may not occur until later in the development of tinnitus. As
      a further control, our experiments compared Arc protein expression between groups
      exposed to the quiet background of a sound-proof chamber to those exposed not
      only to the traumatic noise described above, but also to an intermediate, non
      traumatic noise level (70 dB SPL) for the same duration in each of these three
      brain regions. We found that non-traumatic noise did not up-regulate Arc protein
      expression in these brain regions. To see if changes in Arc expression due to
      acute traumatic noise exposure were stress-related, we compared circulating serum
      corticosterone in controls and rats exposed to traumatic noise at the time when
      changes in Arc were observed, and found no significant differences in this stress
      hormone in our experimental conditions. Finally, the ability of D-cycloserine
      (DCS; an NMDA-receptor NR1 partial agonist) to reduce or prevent the noise trauma
      related plastic changes in the biomarker, Arc, was tested. D-cycloserine
      prevented traumatic noise-induced up-regulation of Arc protein expression in
      amygdala but not in hippocampus, suggesting that DCS alone is not fully effective
      in eliminating regionally-specific early plastic changes after traumatic noise
      exposure.

PMID- 27702573
TI  - Revealing calcium fluxes by analyzing inhibition dynamics in action potential
      clamp.
AB  - In cardiac excitation-contraction coupling (ECC), calcium enters the cytosol via
      L-type Ca2+ channels (LTCC) and reverse Na+/Ca2+-exchange (NCXrev), or is
      released from the sarcoplasmic reticulum (SR) by Ca2+-induced Ca2+-release
      (CICR). The magnitude of Ca2+ influx via the different pathways varies with the
      state of the cell and is difficult to assess quantitatively, because changes in
      Ca2+ influx through one pathway affect the others. In rainbow trout ventricular
      myocytes, the role of the SR has been uncertain for decades. The aim of this work
      was therefore two-fold: 1) to develop a method to quantify the Ca2+ influx
      pathways, and 2) to determine the role of CICR from the SR in trout ventricular
      myocytes. The novelty of our developed method lies in the mathematical analysis
      of measured transsarcolemmal Ca2+ currents and their impact on the corresponding
      Ca2+ transient during gradual inhibition of the currents in action potential (AP)
      clamp. We tested the developed method using an excitation-contraction model and
      showed that the method was able to recover calcium fluxes from noisy synthetic
      data. We applied the approach to trout ventricular myocytes and quantified the
      relative contributions of different Ca2+ influx pathways in ECC and determined
      the kinetics of these fluxes. Under baseline conditions, NCXrev is the main
      transmembrane Ca2+ influx pathway contributing 29 +/- 6% (of the Ca2+ influx),
      LTCC 18 +/- 7%, and CICR 53 +/- 10% to overall Ca2+ transient. Thus, NCXrev is an
      important regulator of contractility and probably plays a role in the negative
      force-frequency relationship of trout ventricular preparations. These results
      demonstrate that trout and neonatal mammalian cardiomyocytes resemble each other
      not only in terms of morphology and energetics but ECC as well. In summary, the
      developed method resolves the major problem how to separate highly interconnected
      fluxes in AP clamp and allows to study Ca2+ fluxes in cardiomyocytes under
      conditions close to in vivo.

PMID- 27702574
TI  - Cell-free analysis of polyQ-dependent protein aggregation and its inhibition by
      chaperone proteins.
AB  - Protein misfolding and aggregation is one of the major causes of
      neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and
      Huntington's disease. So far protein aggregation related to these diseases has
      been studied using animals, cultured cells or purified proteins. In this study,
      we show that a newly synthesized polyglutamine protein implicated in Huntington's
      disease forms large aggregates in HeLa cells, and successfully recapitulate the
      process of this aggregation using a translation-based system derived from HeLa
      cell extracts. When the cell-free translation system was pre-incubated with
      recombinant human cytosolic chaperonin CCT, or the Hsc70 chaperone system
      (Hsc70s: Hsc70, Hsp40, and Hsp110), aggregate formation was inhibited in a dose
      dependent manner. In contrast, when these chaperone proteins were added in a post
      translational manner, aggregation was not prevented. These data led us to suggest
      that chaperonin CCT and Hsc70s interact with nascent polyglutamine proteins co
      translationally or immediately after their synthesis in a fashion that prevents
      intra- and intermolecular interactions of aggregation-prone polyglutamine
      proteins. We conclude that the in vitro approach described here can be usefully
      employed to analyze the mechanisms that provoke polyglutamine-driven protein
      aggregation and to screen for molecules to prevent it.

PMID- 27702576
TI  - Nomenclature for factors of the HLA system, update April 2016.

PMID- 27702575
TI  - Roles of 5-HT1A receptor in the expression of AMPA receptor and BDNF in
      developing mouse cortical neurons.
AB  - The possible interactions between serotonergic and glutamatergic systems during
      neural development and under the pathogenesis of depression remain unclear. We
      now investigated roles of 5-HT1A receptor in the mRNA expression of AMPA receptor
      subunits (GluR1 and GluR2) and brain-derived neurotrophic factor (BDNF) using
      primary culture of cerebral cortex of mouse embryos. Neurons at embryonic day 18
      were cultured for 3days or 14days and then treated with 5-HT1A receptor agonist
      (8-OH-DPAT) for 3h or 24h. In neurons cultured for 3 days, 8-OH-DPAT treatment
      for both 3h and 24h increased the mRNA levels of BDNF and GluR1, but not GluR2.
      In neurons cultured for 14 days, however, 8-OH-DPAT had no effects on these mRNA
      levels. Next, we examined in vivo roles of 5-HT1A receptor by administration of 8
      OH-DPAT to newborn mice. Twenty-four hours after the oral administration of 8-OH
      DPAT, the mRNA expression of BDNF was decreased in the frontal cortex, but had no
      effects on the mRNA expression of GluR1 and GluR2. Taken together, the present
      study suggests that 5-HT1A receptor activation modulates mRNA expression of AMPA
      receptor subunit and BDNF in cortical neurons, and the effects are different
      between in vitro and in vivo.

PMID- 27702577
TI  - Nomenclature for factors of the HLA system, update June 2016.

PMID- 27702578
TI  - Nomenclature for factors of the HLA system, update May 2016.

PMID- 27702579
TI  - Priming with NO controls redox state and prevents cadmium-induced general up
      regulation of methionine sulfoxide reductase gene family in Arabidopsis.
AB  - In the present study we evaluated the pre-treatment (priming) of Arabidopsis
      thaliana plants with sodium nitroprusside (SNP), a NO-donor, as an interesting
      approach for improving plant tolerance to cadmium stress. We focused on the cell
      redox balance and on the methionine sulfoxide reductases (MSR) family as a key
      component of such response. MSR catalyse the reversible oxidation of MetSO
      residues back to Met. Five MSRA genes and nine MSRB genes have been identified in
      A. thaliana, coding for proteins with different subcellular locations. After
      treating 20 days-old A. thaliana (Col 0) plants with 100 MUM CdCl2, increased
      protein carbonylation in leaf tissue, lower chlorophyll content and higher levels
      of reactive oxygen species (ROS) in chloroplasts were detected, together with
      increased accumulation of all MSR transcripts evaluated. Further analysis showed
      reduction in guaiacol peroxidase activity (GPX) and increased catalase (CAT)
      activity, with no effect on ascorbate peroxidase (APX) activity. Pre-exposition
      of plants to 100 MUM SNP before cadmium treatment restored redox balance; this
      seems to be linked to a better performance of antioxidant defenses. Our results
      indicate that NO priming may be acting as a modulator of plant antioxidant system
      by interfering in oxidative responses and by preventing up-regulation of MSR
      genes caused by metal exposure.

PMID- 27702580
TI  - Short ECG segments predict defibrillation outcome using quantitative waveform
      measures.
AB  - AIM: Quantitative waveform measures of the ventricular fibrillation (VF)
      electrocardiogram (ECG) predict defibrillation outcome. Calculation requires an
      ECG epoch without chest compression artifact. However, pauses in CPR can
      adversely affect survival. Thus the potential use of waveform measures is limited
      by the need to pause CPR. We sought to characterize the relationship between the
      length of the CPR-free epoch and the ability to predict outcome. METHODS: We
      conducted a retrospective investigation using the CPR-free ECG prior to first
      shock among out-of-hospital VF cardiac arrest patients in a large metropolitan
      region (n=442). Amplitude Spectrum Area (AMSA) and Median Slope (MS) were
      calculated using ECG epochs ranging from 5s to 0.2s. The relative ability of the
      measures to predict return of organized rhythm (ROR) and neurologically-intact
      survival was evaluated at different epoch lengths by calculating the area under
      the receiver operating characteristic curve (AUC) using the 5-s epoch as the
      referent group. RESULTS: Compared to the 5-s epoch, AMSA performance declined
      significantly only after reducing epoch length to 0.2s for ROR (AUC 0.77-0.74,
      p=0.03) and with epochs of <=0.6s for neurologically-intact survival (AUC 0.72
      0.70, p=0.04). MS performance declined significantly with epochs of <=0.8s for
      ROR (AUC 0.78-0.77, p=0.04) and with epochs <=1.6s for neurologically-intact
      survival (AUC 0.72-0.71, p=0.04). CONCLUSION: Waveform measures predict
      defibrillation outcome using very brief ECG epochs, a quality that may enable
      their use in current resuscitation algorithms designed to limit CPR interruption.

PMID- 27702581
TI  - Characteristics of automated external defibrillator coverage in Philadelphia, PA,
      based on land use and estimated risk.
AB  - AIM: Approximately 424,000 out-of-hospital cardiac arrests (OHCA) occur in the US
      annually. As automated external defibrillators (AED) are an important part of the
      community response to OHCA, we investigated how well the spatial demand
      (likelihood of OHCA) was met by the spatial supply (AEDs) in a dense urban
      environment. METHODS: Using geographic information system (GIS) software, we
      applied kernel density and optimized hot spot procedures with two differently
      sized radii to model OHCA incidence rates from existing studies, providing an
      estimate of OHCA likelihood at a given location. We compared these density maps
      to existing AED coverage in the study area. Descriptive statistics summarized
      coverage by land use. RESULTS: With a 420-ft buffer, we found that 56.0% (79.9%,
      840-ft buffer) of the land area in the city center was covered by existing AEDs
      at, though 70.1 (91.5)% of the OHCA risk was covered using kernel density and
      79.8% (98.1) was covered using hot spot analysis. CONCLUSIONS: The difference in
      coverage by area and risk seems to indicate efficient placement of existing AEDs.
      Our findings also highlight the possible benefits to expanding the influence of
      AEDs by lowering search times, and identify opportunities to improve AED coverage
      in the study area. This article offers one method by which local officials can
      use spatial data to prioritize attention for AED placement and coverage.

PMID- 27702582
TI  - Geminin a multi task protein involved in cancer pathophysiology and developmental
      process: A review.
AB  - DNA replicates in a timely manner with each cell division. Multiple proteins and
      factors are involved in the initiation of DNA replication including a dynamic
      interaction between Cdc10-dependent transcript (Cdt1) and Geminin (GMNN). A
      conformational change between GMNN-Cdt1 heterotrimer and heterohexamer complex is
      responsible for licensing or inhibition of the DNA replication. This molecular
      switch ensures a faithful DNA replication during each S phase of cell cycle. GMNN
      inhibits Cdt1-mediated minichromosome maintenance helicases (MCM) loading onto
      the chromatin-bound origin recognition complex (ORC) which results in the
      inhibition of pre-replication complex assembly. GMNN modulates DNA replication by
      direct binding to Cdt1, and thereby alters its stability and activity. GMNN is
      involved in various stages of development such as pre-implantation, germ layer
      formation, cell commitment and specification, maintenance of genome integrity at
      mid blastula transition, epithelial to mesenchymal transition during
      gastrulation, neural development, organogenesis and axis patterning. GMNN
      interacts with different proteins resulting in enhanced hematopoietic stem cell
      activity thereby activating the development-associated genes' transcription. GMNN
      expression is also associated with cancer pathophysiology and development. In
      this review we discussed the structure and function of GMNN in detail. Inhibitors
      of GMNN and their role in DNA replication, repair, cell cycle and apoptosis are
      reviewed. Further, we also discussed the role of GMNN in virus infected host
      cells.

PMID- 27702583
TI  - EEG asymmetry and BIS/BAS among healthy adolescents.
AB  - Asymmetry in frontal alpha activation (FAA) has been associated with specific
      behavior patterns. Greater activation in the left frontal cortex is related to
      "approach" motivation, while greater activation in the right cortex is associated
      with "withdrawal" motivation. Moreover, resting FAA is stable over time among
      adults. This stability has not been demonstrated among adolescents, and the
      correspondence between resting FAA and personality has been inconsistently
      observed. The present study examined stability of FAA and the association between
      resting FAA and behavioral activation among adolescents. At baseline and 4
      months, 99 adolescents completed a resting electroencephalogram (EEG) and a
      pencil-and-paper measure of personality (BIS/BAS). FAA showed good stability over
      time (Intra-class correlation coefficient=0.65, p<0.001), but there was no
      correlation between FAA and personality. Results are interpreted in light of a
      capability model of FAA; namely, that asymmetry may emerge under conditions of
      stimulation and recede during resting.

PMID- 27702584
TI  - Untrustworthiness inhibits congruent facial reactions to happy faces.
AB  - This study investigated how trustworthiness modulates facial reactions to
      emotional faces, specifically emotional mimicry. In order to manipulate the
      trustworthiness of others, we used the trust game. The participants (N=37)
      perceived the partners as trustworthy or untrustworthy based on whether the
      partners tended to behave fairly or unfairly in the game with a within-subjects
      design. Facial electromyograms were measured while viewing the emotional faces
      displayed by the partners. The results demonstrated that the zygomaticus major
      activity in response to happy faces was greater for the trustworthy partners than
      for the untrustworthy partners. The results suggest that emotional mimicry of
      happiness is more inhibited for those who are non-affiliative and unfavorable,
      such as the untrustworthy partners. On the other hand, there was no effect of
      trustworthiness on congruent facial reactions to sad and angry faces. However,
      the zygomaticus major activity for angry faces was smaller for the trustworthy
      partners than for the untrustworthy partners, suggesting that positive
      expressions to angry faces of the trustworthy partners are inhibited.
      Trustworthiness constructed by social exchange modulates not only emotional
      mimicry for happy faces but also incongruent facial reactions to angry faces.

PMID- 27702585
TI  - Scanning electron microscopic analysis of using agarose hydrogel microenvironment
      to create enamel prism-like tissue on dentine surface.
AB  - OBJECTIVE: To investigate remineralisation of dentine in the hydrogel
      microenvironment for the management of hypersensitivity. METHODS: Human dentine
      slices were prepared from extracted sound human molars. They were acid-etched
      with phosphoric acid and put into the polyethylene tubes. The etched dentine
      surfaces were covered by a 2-mm-thick layer of CaCl2 agarose hydrogel. Another 2
      mm-thick layer of ion-free agarose hydrogel was added on top of the CaCl2 agarose
      hydrogel. They were immersed into a solution containing phosphate and fluoride
      after gelification. The solution was replaced every 24h and the agarose hydrogels
      were replaced every 48h. Scanning electron microscopy (SEM), X-ray diffraction
      (XRD) and Fourier transform infrared spectroscopy (FTIR) were used to evaluate
      the formed crystals on dentine surface after 2, 4 and 6days. SEM was used to
      study the mineral formed in the replaced agarose hydrogels. RESULTS: Observation
      under SEM showed that crystals occluded the dentinal tubules and an enamel prism
      like tissue formed on the etched dentine surface. XRD and FTIR analyses confirmed
      the crystals were hydroxyapatite. Numerous calcium phosphate globules were found
      in the replaced calcium chloride agarose hydrogel. CONCLUSION: The hydrogel acts
      as the remineralisation microenvironment to initiate occlusion of dentinal
      tubules and formation of enamel prisms-like tissue on human dentine surface.
      CLINICAL SIGNIFICANCE: Remineralisation of dentine induced in this hydrogel
      microenvironment can be an alternative therapeutic technique for the management
      of dentine hypersensitivity.

PMID- 27702586
TI  - Physiological effects of a habituation procedure for functional MRI in awake mice
      using a cryogenic radiofrequency probe.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) in mice is typically
      performed under anesthesia due to difficulties in holding the head of awake mice
      stably with a conventional three-point fixation method that uses a tooth-bar and
      earplugs. Although some studies have succeeded in fMRI in awake mice by attaching
      a head-post on the skull, this cannot be applied to fMRI using a high signal-to
      noise ratio (SNR) cryogenic MRI-detector, CryoProbe, because it covers the head
      of a mouse closely. NEW METHOD: We developed head-fixation implements for awake
      mice that are applicable to fMRI using CryoProbe. RESULTS: A head-bar was
      surgically attached to the skull of a mouse that was then habituated to a mock
      fMRI-environment, two hours/day for eight days with physiological examinations of
      body-weight, fecal weight, electromyogram (EMG), and electrocardiogram. EMG power
      decreased with just one day of habituation, whereas heart rate decreased after at
      least seven days of habituation. Estimated head motions of awake mice during fMRI
      were significantly smaller than a voxel size. Unexpectedly, temporal SNR of fMRI
      signals for awake mice was higher than that for anesthetized mice held by a
      conventional method. Functional connectivity in the brain of both anesthetized
      and awake mice showed bilateral and unilateral networks. COMPARISON WITH EXISTING
      METHOD(S): fMRI using CryoProbe had been performed on anesthetized mice
      previously. Our method does not use anesthetics during habituation or fMRI.
      CONCLUSION: Our method would be beneficial for translational research using fMRI
      in mice and humans because human fMRI is typically performed without anesthetics.

PMID- 27702587
TI  - Using EP50 to forecast treatment adherence in individuals with multiple
      sclerosis.
AB  - Much like delay discounting, probability discounting may be related to a host of
      pro-health behaviors. In a recent report, a Medical Decision Making Questionnaire
      (MDMQ) was developed that leveraged this insights of probability discounting to
      both describe ways that multiple sclerosis (MS) patients weigh costs and benefits
      when making adherence choices, and predicted their self-reported treatment
      adherence. The current re-analysis of those data use a novel EP50 measure as a
      framework of a model that predicted the cost/benefit ratios necessary for the
      choices of typically non-adherent patients to become indistinguishable from those
      of typically adherent patients (and vice versa). These analytic tools may aid in
      the development/evaluation of both novel therapeutics and treatment adherence
      strategies for chronic conditions.

PMID- 27702588
TI  - Self-control mediates the relationship between time perspective and BMI.
AB  - Trait future time perspective measures the extent to which behaviour is dominated
      by a striving for future goals and rewards. Trait present time perspective
      measures orientation towards immediate pleasure. Previous research has explored
      the relationship between future and present time perspective and BMI with mixed
      findings. In addition, the psychological mechanism underlying this relationship
      is unclear. Self-control is a likely candidate, as it has been related to both
      BMI and time perspective, but the relationship between all of these concepts has
      not been examined in a single study. Therefore, the aim of this study was to
      examine if trait self-control mediates the relationship between time perspective
      (future and present) and BMI. Self-report time perspective (ZTPI), self-control
      (SCS) and height/weight data were collected using an online survey from a mixed
      student and community sample (N = 218) with wide ranging age (mean 29, SD 11,
      range 18-73 years) and BMI (mean 24, SD 4, range 15-43). The results of a
      structural equation model including both facets of time perspective suggested
      that the traits are related yet distinct measures that independently predict BMI
      through changes in self-control. Bootstrap mediation analysis showed that self
      control mediated the relationship between both future time perspective (95% CI, 
      0.10 to -0.02) and present time perspective (95% CI, 0.03 to 0.17), and BMI in
      opposite directions. Participants with higher future time perspective scores
      (higher present time perspective scores) had higher (lower) self-control, which
      predicted lower (higher) BMI. These results are consistent with previous research
      suggesting an important role for time perspective in health outcomes. Self
      control likely mediates the relationship between temporal perspectives and BMI,
      suggesting that time perspective may be a target for individualised
      interventions.

PMID- 27702589
TI  - Electrochemistry of cytochrome P450 17alpha-hydroxylase/17,20-lyase (P450c17).
AB  - Within the superfamily of cytochrome P450 enzymes (P450s), there is a small class
      which is functionally employed for steroid biosynthesis. The enzymes in this
      class appear to have a small active site to accommodate the steroid substrates
      specifically and snuggly, prior to the redox transformation or hydroxylation to
      form a product. Cytochrome P450c17 is one of these and is also a multi-functional
      P450, with two activities, the first 17alpha-hydroxylation of pregnenolone is
      followed by a subsequent 17,20-lyase transformation to dehydroepiandrosterone
      (DHEA) as the dominant pathways to cortisol precursors or androgens in humans,
      respectively. How P450c17 regulates these two redox reactions is of special
      interest. There is a paucity of direct electrochemical studies on steroidogenic
      P450s, and in this mini-review we provide an overview of these studies with
      P450c17. Historical consideration as to the difficulties in obtaining reliable
      electrochemistry due to issues of handling proteins on an electrode, together
      with advances in the electrochemical techniques are addressed. Recent work using
      Fourier transformed alternating current voltammetry is highlighted as this
      technique can provide both catalytic information simultaneously with the
      underlying redox transfer with the P450 haem.

PMID- 27702590
TI  - Annexin A6 regulates adipocyte lipid storage and adiponectin release.
AB  - Lipid storage and adipokine secretion are critical features of adipocytes.
      Annexin A6 (AnxA6) is a lipid-binding protein regulating secretory pathways and
      its role in adiponectin release was examined. The siRNA-mediated AnxA6 knock-down
      in 3T3-L1 preadipocytes impaired proliferation, and differentiation of AnxA6
      depleted cells to mature adipocytes was associated with higher soluble
      adiponectin and increased triglyceride storage. The latter was partly attributed
      to reduced lipolysis. Accordingly, AnxA6 overexpression in 3T3-L1 adipocytes
      lowered cellular triglycerides and adiponectin secretion. Indeed, serum
      adiponectin was increased in AnxA6 deficient mice. Expression analysis identified
      AnxA6 protein to be more abundant in intra-abdominal compared to subcutaneous
      adipose tissues of mice and men. AnxA6 protein levels increased in white adipose
      tissues of obese mice and here, levels were highest in subcutaneous fat. AnxA6
      protein in adipocytes was upregulated by oxidative stress which might trigger
      AnxA6 induction in adipose tissues and contribute to impaired fat storage and
      adiponectin release.

PMID- 27702591
TI  - Montelukast ameliorates streptozotocin-induced cognitive impairment and
      neurotoxicity in mice.
AB  - Extensive studies have demonstrated that neuroinflammation is associated with
      Alzheimer's disease (AD) and cysteinyl leukotriene receptor 1 (CysLT1R) was
      involved in neuroinflammation. Montelukast, a highly selective CysLT1R
      antagonist, has been reported to attenuate learning and memory impairments in the
      amyloid-beta-induced mouse model of AD. However, whether montelukast also exerts
      beneficial effects on streptozotocin (STZ)-induced memory deficits in mice is not
      well known. In the present study, we aimed to investigate the effects of
      montelukast on STZ-induced cognitive impairment, neuroinflammation and apoptosis
      in mice. Our data showed that intra-hippocampal microinfusion of STZ resulted in
      learning and memory impairments, including increased escape latency during
      acquisition trials and decreased exploratory activities in the probe trial in
      Morris watermaze (MWM) task, and decreased number of correct choices and
      increased latency to enter the shock-free compartment in Y-maze test, and caused
      neuroinflammatory and apoptotic responses, evidenced by increments of nuclear NF
      kappaB p65, TNF-alpha, IL-1beta, cleaved caspase-3, Bax as well as decreased
      expression of Bcl-2 in hippocampus. Interestingly, STZ treatment led to up
      regulation of protein and mRNA of CysLT1R in hippocampus. Of note, consecutive
      oral administration of montelukast (1 or 2mg/kg, 3 weeks) remarkably attenuated
      these effects induced by STZ. However, montelukast had no effect on normal mice.
      These results suggest that montelukast improves memory impairment and inhibits
      neuroinflammation and apoptosis in mice exposed to STZ. Montelukast may provide a
      novel strategy for treating or preventing AD.

PMID- 27702592
TI  - Alpha-naphthylisothiocyanate impairs bile acid homeostasis through AMPK-FXR
      pathways in rat primary hepatocytes.
AB  - Alpha-naphthylisothiocyanate (ANIT) is widely used to induce cholestasis in basic
      researches. Although direct damage induced by ANIT to bile duct epithelial cells
      has been documented in previous studies, few works investigated ANIT-induced
      effects on hepatocytes. Our previous study indicated that activated AMP-activated
      protein kinase (AMPK) inhibited farnesoid X receptor (FXR) expression and further
      participated in the pathogenesis of estrogen-induced cholestasis. However,
      whether ANIT has effects on bile acid homeostasis in hepatocytes, and the role of
      AMPK-FXR pathway played in these effects remain unclear. In this study, our
      results showed that ANIT induced intracellular bile acid accumulation without
      obvious cellular toxicity in sandwich cultured rat primary hepatocytes (SCRHs),
      accompanied with significant decreased expression of FXR and bile acid
      transporters. AMPK activation via ERK1/2-LKB1 pathway was critical for ANIT
      induced effects on hepatocytes. Compound C, specific AMPK inhibitor, blocked ANIT
      regulated gene expression, decreased bile acid accumulation and recovered bile
      canalicular structure both in vitro and in vivo. Furthermore, the expression of
      A1 adenosine receptor (A1AR), a potential cholestatic target, was relatively low
      in hepatocytes compared with expression in rat whole livers. Consistent with
      these findings, DPCPX, a classic antagonist of A1AR, had no effect on ANIT
      induced hepatocytes injury. In summary, our results indicate that AMPK-FXR
      signaling is critical for ANIT-induced toxic effects on hepatocytes, provide new
      insights into the pathogenesis of ANIT-induced cholestasis, and suggest AMPK-FXR
      pathway as a potential therapeutic target for cholestasis.

PMID- 27702593
TI  - Lipids and flaviviruses, present and future perspectives for the control of
      dengue, Zika, and West Nile viruses.
AB  - Flaviviruses are emerging arthropod-borne pathogens that cause life-threatening
      diseases such as yellow fever, dengue, West Nile encephalitis, tick-borne
      encephalitis, Kyasanur Forest disease, tick-borne encephalitis, or Zika disease.
      This viral genus groups >50 viral species of small enveloped plus strand RNA
      virus that are phylogenetically closely related to hepatitis C virus.
      Importantly, the flavivirus life cycle is intimately associated to host cell
      lipids. Along this line, flaviviruses rearrange intracellular membranes from the
      endoplasmic-reticulum of the infected cells to develop adequate platforms for
      viral replication and particle biogenesis. Moreover, flaviviruses dramatically
      orchestrate a profound reorganization of the host cell lipid metabolism to create
      a favorable environment for viral multiplication. Consistently, recent work has
      shown the importance of specific lipid classes in flavivirus infections. For
      instances, fatty acid synthesis is linked to viral replication,
      phosphatidylserine and phosphatidylethanolamine are involved on the entry of
      flaviviruses, sphingolipids (ceramide and sphingomyelin) play a key role on virus
      assembly and pathogenesis, and cholesterol is essential for innate immunity
      evasion in flavivirus-infected cells. Here, we revise the current knowledge on
      the interactions of the flaviviruses with the cellular lipid metabolism to
      identify potential targets for future antiviral development aimed to combat these
      relevant health-threatening pathogens.

PMID- 27702594
TI  - Structure and functionality of nanostructured triacylglycerol crystal networks.
AB  - In this review, recent advances in the characterization of the nanoscale
      structure of fat crystal networks are outlined. The effect of different factors
      on the properties of crystalline nanoplatelets (CNPs) is comprehensively
      described. These are discussed together with the observed changes in polymorphism
      and micro- or mesostructural properties so as to have a complete understanding of
      the influence of different internal and external factors on the material
      properties of fats. The relationship between the nanostructure and the material
      properties of fats (i.e., oil binding capacity and rheology) is also described.
      Characterization of the nanostructure of fats has provided a new dimension to the
      analysis of fat crystal networks and opportunities for nanoengineering that could
      result in innovations in the food industry with regards to processing and
      structuring fatty materials.

PMID- 27702595
TI  - Smart nanoparticles with a detachable outer shell for maximized synergistic
      antitumor efficacy of therapeutics with varying physicochemical properties.
AB  - Co-delivery systems capable of transporting hydrophobic chemotherapeutics and
      hydrophilic siRNA to the same cell population with simultaneous burst release of
      both drugs to maximize synergistic anticancer efficacy remains elusive. In this
      light, a multifunctional nanoparticle (HA-PSR) consisting of a redox-sensitive
      core and detachable crosslinked hyaluronic acid (HA) shell was developed. Octyl
      modified PEI containing disulfide linkages (PSR) were synthesized as the core
      materials for co-encapsulation of chemotherapeutics and siRNA, while a HAase
      sensitive thiolated HA (HA-SH) was collaboratively assembled to the anionic shell
      for CD44-mediated active targeting along with enhanced and detachable protection
      for drug loaded inner cores. Resultantly, HA de-protected redox-sensitive inner
      cores achieved co-burst release of both cargoes when triggered by glutathione
      (GSH) rich environments in cytoplasm. Results of in-vivo and in-vitro testing
      indicated successful co-encapsulation of hydrophobic drugs and hydrophilic siRNA
      with adjustable ratios. Selective delivery to CD44 overexpressing tumors was
      achieved through passive and active targeting, followed by HAase-triggered HA de
      shielding and GSH-triggered burst release of both cargos. Rapid intracellular
      trafficking maximized synergistic cytotoxicities of chemotherapeutics and siRNA
      for remarkable tumor inhibition in a xenograft animal tumor model. Consequently,
      the HA-PSR nanoparticle holds great potential for combined
      chemotherapeutics/siRNA treatment in cancer with maximized synergistic antitumor
      efficacy.

PMID- 27702596
TI  - DNA damage-induced inflammation and nuclear architecture.
AB  - Nuclear architecture and the chromatin state affect most-if not all- DNA
      dependent transactions, including the ability of cells to sense DNA lesions and
      restore damaged DNA back to its native form. Recent evidence points to functional
      links between DNA damage sensors, DNA repair mechanisms and the innate immune
      responses. The latter raises the question of how such seemingly disparate
      processes operate within the intrinsically complex nuclear landscape and the
      chromatin environment. Here, we discuss how DNA damage-induced immune responses
      operate within chromatin and the distinct sub-nuclear compartments highlighting
      their relevance to chronic inflammation.

PMID- 27702597
TI  - Sequence learning in Parkinson's disease: Focusing on action dynamics and the
      role of dopaminergic medication.
AB  - Previous studies on movement sequence learning in Parkinson's disease (PD) have
      produced mixed results. A possible explanation for the inconsistent findings is
      that some studies have taken dopaminergic medication into account while others
      have not. Additionally, in previous studies the response modalities did not allow
      for an investigation of the action dynamics of sequential movements as they
      unfold over time. In the current study we investigated sequence learning in PD by
      specifically considering the role of medication status in a sequence learning
      task where mouse movements were performed. The focus on mouse movements allowed
      us to examine the action dynamics of sequential movement in terms of initiation
      time, movement time, movement accuracy, and velocity. PD patients performed the
      sequence learning task once on their regular medication, and once after overnight
      withdrawal from their medication. Results showed that sequence learning as
      reflected in initiation times was impaired when PD patients performed the task ON
      medication compared to OFF medication. In contrast, sequence learning as
      reflected in the accuracy of movement trajectories was enhanced when performing
      the task ON compared to OFF medication. Our findings suggest that while
      medication enhances execution processes of movement sequence learning, it may at
      the same time impair planning processes that precede actual execution. Overall,
      the current study extends earlier findings on movement sequence learning in PD by
      differentiating between various components of performance, and further refines
      previous dopamine overdose effects in sequence learning.

PMID- 27702598
TI  - Juvenile Granulosa Cell Tumor of the Ovary: A Clinicopathologic Study.
AB  - STUDY OBJECTIVE: To report on the clinical characteristics and outcome of
      pediatric patients with juvenile granulosa cell tumor (JGCT) of the ovary.
      DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Patients
      with histopathologically confirmed ovarian JGCT diagnosed between 1990 and 2016
      were identified. Data on the clinical presentation, surgical management,
      oncologic management, laboratory investigation, follow-up, and outcome were
      collected. Tumors were staged according to the International Federation of
      Gynecology and Obstetrics criteria. RESULTS: Eight patients were diagnosed with
      ovarian JGCT during the study period. The median age at presentation was 3 years
      (range, 0.7-14 years). Precocious puberty was the presenting symptom in all five
      prepubertal children; abdominal distension due to mass effect was the presenting
      symptom in three children older than 9 years of age. In patients who had
      preoperative serologic testing, estradiol (n = 3) and inhibin (n = 3) levels were
      elevated. Five patients had stage I disease, and three had stage III. All stage I
      patients underwent salpingo-oophorectomy as the only treatment. Stage III
      patients received adjuvant chemotherapy. After a median follow-up of 6.2 years,
      six patients (75%) were alive without evidence of disease. One stage I patient
      with germline p53 mutation and phosphatase and tensin homolog mutation, died
      because of subsequent liposarcoma. One patient with stage IIIB disease developed
      recurrence detected according to an elevated inhibin serum level, and died due to
      progressive disease despite receiving multiple chemotherapy regimens. CONCLUSION:
      Juvenile granulosa cell tumor has a favorable prognosis in patients with stage I
      disease after surgical resection alone. Adjuvant chemotherapy might be indicated
      in patients with higher-stage tumors.

PMID- 27702599
TI  - Autonomic changes induced by provocative motion in rats bred for high (HAB) and
      low (LAB) anxiety-related behavior: Paradoxical responses in LAB animals.
AB  - In humans, associations between anxiety and nausea (including motion-induced) are
      reported but the underlying mechanisms are not known. Hypothermia is proposed to
      be an index of nausea in rats. Utilising hypothermia and heart rate as outcome
      measures we investigated the response to provocative motion in rats selectively
      bred for high (HAB) and low (LAB) anxiety-related behaviors and in non-selected
      (NAB) rats to further elucidate the potential relationship between hypothermia
      and nausea-like state. Core temperature and electrocardiogram were monitored in
      each group (n=10 per group) using telemetry, with or without circular motion
      (40min; 0.75Hz) and vehicle or diazepam (2mg/kg, i.p.) pre-treatment. Heart rate
      and time- and frequency-domain parameters of heart rate variability were derived
      from the electrocardiogram. There was no baseline difference in core temperature
      between the three groups (mean 38.0+/-0.1 degrees C), but HAB animals had a
      significantly lower resting heart rate (330+/-7bpm) compared to LAB (402+/-5bpm)
      and NAB (401+/-9bpm). Animals in all groups exhibited hypothermia during motion
      (HAB: 36.3+/-0.1 degrees C; NAB: 36.4+/-0.1 degrees C; LAB: 34.9+/-0.2 degrees C)
      with the magnitude (area under the curve, AUC) of the response during 40-min
      motion being greater in LAB compared to NAB and HAB rats, and this was also the
      case for the motion-induced bradycardia. Diazepam had minimal effects on baseline
      temperature and heart rate in all groups, but significantly reduced the
      hypothermia response (AUC) to motion in all groups by ~30%. Breeding for extremes
      in anxiety-related behavior unexpectedly selects animals with low trait anxiety
      that have enhanced bradycardia and hypothermic responses to motion; consequently,
      this animal model appears to be not suitable for exploring relationships between
      anxiety and autonomic correlates of nausea. Thermal and cardiovascular responses
      to motion were little different between HAB and NAB rats indicating that either
      hypothermia is not an index of a nausea-like state in rats, or that the positive
      correlation between anxiety and nausea demonstrated in humans does not exist in
      rats. The mechanism underlying the enhanced physiological responses in LAB
      requires more detailed study and may provide a novel model to investigate factors
      modulating motion sensitivity.

PMID- 27702600
TI  - Evaluation of neuron-glia integrity by in vivo proton magnetic resonance
      spectroscopy: Implications for psychiatric disorders.
AB  - Proton magnetic resonance spectroscopy (1H-MRS) has been widely applied in human
      studies. There is now a large literature describing findings of brain MRS studies
      with mental disorder patients including schizophrenia, bipolar disorder, major
      depressive disorder, and anxiety disorders. However, the findings are mixed and
      cannot be reconciled by any of the existing interpretations. Here we proposed the
      new theory of neuron-glia integrity to explain the findings of brain 1H-MRS
      stuies. It proposed the neurochemical correlates of neuron-astrocyte integrity
      and axon-myelin integrity on the basis of update of neurobiological knowledge
      about neuron-glia communication and of experimental MRS evidence for impairments
      in neuron-glia integrity from the authors and the other investigators. Following
      the neuron-glia integrity theories, this review collected evidence showing that
      glutamate/glutamine change is a good marker for impaired neuron-astrocyte
      integrity and that changes in N-acetylaspartate and lipid precursors reflect
      impaired myelination. Moreover, this new theory enables us to explain the
      differences between MRS findings in neuropsychiatric and neurodegenerative
      disorders.

PMID- 27702601
TI  - Towards universal approach for bacterial production of three-finger Ly6/uPAR
      proteins: Case study of cytotoxin I from cobra N. oxiana.
AB  - Cytotoxins or cardiotoxins is a group of polycationic toxins from cobra venom
      belonging to the 'three-finger' protein superfamily (Ly6/uPAR family) which
      includes small beta-structural proteins (60-90 residues) with high disulfide bond
      content (4-5 disulfides). Due to a high cytotoxic activity for cancer cells,
      cytotoxins are considered as potential anticancer agents. Development of the high
      throughput production methods is required for the prospective applications of
      cytotoxins. Here, efficient approach for bacterial production of recombinant
      analogue of cytotoxin I from N. oxiana containing additional N-terminal Met
      residue (rCTX1) was developed. rCTX1 was produced in the form of E. coli
      inclusion bodies. Refolding in optimized conditions provided ~6 mg of correctly
      folded protein from 1 L of bacterial culture. Cytotoxicity of rCTX1 for C6 rat
      glioma cells was found to be similar to the activity of wild type CTX1. The
      milligram quantities of 13C,15N-labeled rCTX1 were obtained. NMR study confirmed
      the similarity of the spatial structures of recombinant and wild-type toxins.
      Additional Met residue does not perturb the overall structure of the three-finger
      core. The analysis of available data for different Ly6/uPAR proteins of snake and
      human origin revealed that efficiency of their folding in vitro is correlated
      with the number of proline residues in the third loop and the surface area of
      hydrophobic residues buried within the protein interior. The obtained data
      indicate that hydrophobic core is important for the folding of proteins with high
      disulfide bond content. Developed expression method opens new possibilities for
      structure-function studies of CTX1 and other related three-finger proteins.

PMID- 27702602
TI  - Proteocephalid tapeworms (Cestoda: Onchoproteocephalidea) of loaches
      (Cobitoidea): Evidence for monophyly and high endemism of parasites in the Far
      East.
AB  - The parasite fauna of loaches (Cypriniformes: Cobitoidea), a group of small
      bottom-dwelling freshwater fishes with a mostly Eurasian distribution, remains a
      largely unknown quantity. Here we revise the taxonomy of tapeworms of the genus
      Proteocephalus Weinland, 1858 (Cestoda: Proteocephalidae) that had been found in
      loaches from the Palaearctic Region (Central Europe, Japan and Russia [Primorsky
      Region]). Molecular phylogenetic analysis based on two nuclear (ssr- and lsrDNA)
      and two mitochondrial genes (cox1 and rrnL) revealed a monophyletic group
      consisting of four valid species nesting within the Proteocephalus-aggregate: (i)
      Proteocephalus sagittus (Grimm, 1872) from Barbatula barbatula (Europe, Russia
      and Tajikistan), (ii) Proteocephalus demshini n. sp. from Barbatula toni (Russian
      Far East - Primorsky Region), (iii) Proteocephalus midoriensis Shimazu, 1990 from
      Lefua echigonia (Japan) and L. costata (Russia) (new host and geographical
      record), and (iv) Proteocephalus misgurni n. sp. from Misgurnus anguillicaudatus
      (Russia; Primorsky Region). Proteocephalus sagittus and P. demshini, and P.
      midoriensis and P. misgurni were recovered as sister taxa, respectively.
      Proteocephalus sagittus and P. demshini are characterized by having proglottids
      that are wider than long, an elongate to pyriform cirrus-sac and the vitelline
      follicles that form wide lateral bands. Proteocephalus midoriensis and P.
      misgurni are characterized by having proglottids that are more elongate and an
      ovoid to almost spherical cirrus-sac and the vitelline follicles forming narrow
      lateral bands. Proteocephalus demshini differs from P. sagittus in the
      posterolateral extent of the vitelline follicles, whereas P. misgurni can be
      distinguished from P. midoriensis mainly by the relative size of the ovary,
      posterior extent of the vitelline follicles and width of the scolex. Unlike most
      species of the Proteocephalus-aggregate that possess an apical sucker, all
      species from loaches are devoid of any apical organ. The existence of two new
      species in loaches from the Primorsky Region of Russia indicates high endemism of
      fish parasites in this region. A key to the identification of recognized species
      from loaches is provided.

PMID- 27702603
TI  - Isoliquiritigenin exhibits anti-proliferative properties in the pituitary
      independent of estrogen receptor function.
AB  - The plant flavonoid isoliquiritigenin (ISL) is a botanical estrogen widely taken
      as an herbal supplement to ease the symptoms of menopause. ISL has been also
      shown to have anti-tumor properties in a number of cancer cell backgrounds.
      However, the effects of ISL on normal cells are less well known and virtually
      unstudied in the context of the pituitary gland. We have established a pituitary
      explant culture model to screen chemical agents for gene expression changes
      within the pituitary gland during a period of active proliferation and
      differentiation. Using this whole-organ culture system we found ISL to be weakly
      estrogenic based on its ability to induce Cckar mRNA expression, an estrogen
      receptor (ER) mediated gene. Using a range of ISL from 200nM to 200MUM, we
      discovered that ISL promoted cell proliferation at a low concentration, yet
      potently inhibited proliferation at the highest concentration. ICI 182,780 failed
      to antagonize ISL's repression of pituitary cell proliferation, indicating the
      effect is independent of ER signaling. Coincident with a decrease in
      proliferating cells, we observed down-regulation of transcript for cyclin D2 and
      E2 and a strong induction of mRNA and protein for the cyclin dependent kinase
      inhibitor Cdkn1a (p21). Importantly, high dose ISL did not alter the balance of
      progenitor vs. differentiated cell types within the pituitary explants and they
      seemed otherwise healthy; however, TUNEL staining revealed an increase in
      apoptotic cell death in ISL treated cultures. Our results merit further
      examination of ISL as an anti-tumor agent in the pituitary gland.

PMID- 27702604
TI  - Evaluation of MALDI-TOF MS (Matrix-Assisted Laser Desorption-Ionization Time-of
      Flight Mass Spectrometry) for routine identification of anaerobic bacteria.
AB  - Information regarding the use of MALDI-TOF MS as an alternative to conventional
      laboratory methods for the rapid and reliable identification of bacterial
      isolates is still limited. In this study, MALDI-TOF MS was evaluated on 295
      anaerobic isolates previously identified by 16S rRNA gene sequencing and with
      biochemical tests (Rapid ID 32A system, BioMerieux). In total, 85.8% of the
      isolates were identified by MALDI-TOF MS at the species level vs 49.8% using the
      Rapid ID 32A system (p < 0.0001). None of the isolates was discordantly
      identified at the genus level using MALDI-TOF MS and only 9 of them could not be
      identified using the method. Thus, our results show that MALDI-TOF MS is a robust
      and reliable tool for the identification of anaerobic isolates in the
      microbiology laboratory. Its implementation will reduce the turnaround time for a
      final identification and the number of isolates that require 16S rRNA sequencing.

PMID- 27702605
TI  - In-vivo high resolution AFM topographic imaging of Caenorhabditis elegans reveals
      previously unreported surface structures of cuticle mutants.
AB  - Atomic force microscopy (AFM) is a powerful method for topographic imaging of
      surfaces with nanometer resolution. AFM offers significant advantages over
      scanning electron microscopy (SEM) including the acquisition of quantitative 3D
      images and biomechanical information. More importantly, for in-vivo biological
      imaging, AFM does not require sample dehydration/labeling. We show for the first
      time high-resolution topographical images of the cuticle of the model organism C.
      elegans under physiological conditions using AFM. C. elegans is used extensively
      for drug screening and to study pathogen adherence in innate immunity; both
      applications highly depend on the integrity of the nematode's cuticle. Mutations
      affecting both drug adsorption and pathogen clearance have been proposed to
      relate to changes in the cuticle structure, but never visually examined in high
      resolution. In this study we use AFM to visualize the topography of wild-type
      adult C. elegans as well as several cuticle collagen mutants and describe
      previously unseen anatomical differences.

PMID- 27702606
TI  - Nanotheranostic approaches for management of bloodstream bacterial infections.
AB  - Bloodstream bacterial infections are a serious threat to global public health and
      economy. The recent figures released by National Center for Health Statistics
      indicate that more than a million Americans get affected by it each year and the
      sepsis mortality alone is about 28%-50% Hall et al. (2011).1 Robust and
      affordable point-of-care medical technologies are, therefore, urgently needed for
      rapid decision-making to initiate appropriate line of treatment. Current
      techniques based on blood culture and serology do not have quick turnaround times
      or adequate sensitivities for early intervention. Moreover, antimicrobial
      resistance poses a great challenge in the fight towards effective bacterial
      infection management. Nanotheranostics is emerging as a novel strategy combining
      solutions for rapid diagnosis and treatment in a more personalized way. This
      review highlights the recent advances made in theranosis of bloodstream bacterial
      infections using different classes of nanomaterials and bioreceptors, and
      discusses present challenges and future way forward.

PMID- 27702607
TI  - Development and diabetes on the fly.
AB  - We review the use of a model organism to study the effects of a slow course,
      degenerative disease: namely, diabetes mellitus. Development and aging are
      biological phenomena entailing reproduction, growth, and differentiation, and
      then decline and progressive loss of functionality leading ultimately to failure
      and death. It occurs at all biological levels of organization, from molecular
      interactions to organismal well being and homeostasis. Yet very few models
      capable of addressing the different levels of complexity in these chronic,
      developmental phenomena are available to study, and model organisms are an
      exception and a welcome opportunity for these approaches. Genetic model
      organisms, like the common fruit fly, Drosophila melanogaster, offer the
      possibility of studying the panoply of life processes in normal and diseased
      states like diabetes mellitus, from a plethora of different perspectives. These
      long-term aspects are now beginning to be characterized.

PMID- 27702608
TI  - Multifaceted properties of 1,4-dimethylcarbazoles: Focus on trimethoxybenzamide
      and trimethoxyphenylurea derivatives as novel human topoisomerase II inhibitors.
AB  - Natural or synthetic carbazole derivatives have recently attracted the attention
      of the scientific world because of their multiple biological activity, leading to
      an increase of designed, synthesized and studied analogues. In this paper, four
      1,4-dimethylcarbazole derivatives, analogues of Ellipticine, have been
      investigated for their ability to block cancer cells growth, with low effects on
      the proliferation of normal cells. DNA topoisomerases inhibition assays, docking
      simulations, stability studies and effects on a membrane model are reported.
      Particularly, compounds 2 and 3 have been found thermally stable and able to
      inhibit, strongly and selectively, the human DNA topoisomerase II. These
      properties confer a good and broad antitumoral activity in vitro, with very low
      cytotoxic effect on the proliferation of normal cell lines and without damaging,
      in contrast with Ellipticine, the cell membrane model. The presented outcomes set
      the most active compounds as good candidates for pre-clinical studies useful in
      cancer treatment.

PMID- 27702609
TI  - Enhancing the efficiency of thiomers: Utilizing a highly mucoadhesive polymer as
      backbone for thiolation and preactivation.
AB  - The objective of this study was to develop a novel thiomer with enhanced
      mucoadhesive properties using a highly mucoadhesive polymeric backbone. FixomerTM
      A-30 (poly(methacrylic acid-co-sodium acrylamidomethyl propane sulfonate)),
      exhibiting a mucoadhesive strength superior to that of all other polymers, was
      thiolated by conjugation with l-cysteine and furthermore preactivated with 2
      mercaptonicotinic acid (MNA). The resulting derivatives Fix-SH and Fix-S-MNA
      exhibited coupling rates of 755MUmol thiol groups and 304MUmol MNA per gram
      polymer, respectively. The mucoadhesive profile was evaluated with three
      different methods: tensile studies, rotating cylinder and rheological synergism.
      In tensile studies, a total work of adhesion of above 500MUJ was determined for
      the unmodified polymer that increased to around 750MUJ after thiolation and
      around 1500MUJ after preactivation. The adhesion time of Fix-SH on the rotating
      cylinder was 3.7-fold and that of Fix-S-MNA 6.8-fold longer compared to the
      unmodified polymer. A rheological synergism was observed for the unmodified
      polymer as well as the derivatives with a non-significant difference for Fix-SH
      but a 5.44-fold improvement for Fix-S-MNA. Fix-S-MNA showed a significantly
      improved swelling behavior with a water-uptake up to the 30-fold of its initial
      weight over >50h whereas thiolation showed only slight improvements.
      Derivatization had no significant influence on cell viability. According to the
      results, Fix-S-MNA seems to be a suitable polymer for mucoadhesive drug delivery
      systems.

PMID- 27702611
TI  - Long-term home monitoring of intraocular pressure in pediatric glaucoma.
AB  - PURPOSE: Diurnal fluctuation of intraocular pressure (IOP), implicated in
      progression of adult glaucoma, has been reported in children only in the context
      of office and short-term home monitoring. The purpose of this study was to
      evaluate long-term patterns of IOP fluctuation and changes resulting from outflow
      enhancing intervention in pediatric glaucoma. METHODS: Parent-measured home-based
      rebound tonometry (Icare, Finland Oy) in pediatric glaucoma patients was studied
      prospectively. IOP was monitored for more than 1 month, with requested
      measurements at least 3 times daily. Demographic and glaucoma-related information
      were collected for each participant. IOP was recorded at home on electronic data
      sheets. It was then evaluated for trends including mean overall IOP, IOP pre- and
      post-planned IOP-lowering interventions, and IOP spikes over determined time
      intervals. RESULTS: IOP was measured in 14 eyes of 7 children (mean age, 9.3 +/-
      2.4 years) over a mean of 164.3 days (range, 75-341), with a mean of 2.46
      readings daily. Six eyes of 5 children underwent attempted outflow improvement,
      with improved mean IOP before versus after intervention (26.6 vs 15.5 mm Hg, P <
      0.0001) and decreased mean daily IOP fluctuation (8.4 vs 4.6 mm Hg, P < 0.001)
      for each. An IOP reading 20% greater than mean for an individual eye over the
      entire period (a pressure "spike") occurred in 19.3 +/- 6.7% over 1 day, 62.9 +/-
      18.0% over 3 days, 80.8 +/- 12.2% over 7 days, and 92.9 +/- 9.4% over 14 days.
      CONCLUSIONS: Long-term home monitoring in pediatric glaucoma proved feasible in
      this study population and often demonstrated large IOP fluctuations. A 14-day
      period of home monitoring provided >90% chance of identifying an IOP spike.
      Successful outflow improvement lowered both mean IOP and mean daily IOP
      fluctuations.

PMID- 27702612
TI  - Impact of number and quality of retinal images in a telemedicine screening
      program for ROP: results from the e-ROP study.
AB  - BACKGROUND: Telemedicine for the detection of retinopathy of prematurity (ROP) is
      becoming increasingly common; however, obtaining the required multiple retinal
      images from an infant can be challenging. This secondary analysis from the
      Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e
      ROP) study evaluated the detection of referral-warranted ROP (RW-ROP) by trained
      readers when a full set of 5 retinal images could not be obtained. METHODS: A
      total of 7,905 image sets from 1,257 infants in the study were evaluated. Retinal
      location of images and image quality were recorded. Sensitivity and specificity
      of RW-ROP detection by trained readers were calculated by comparing findings in
      incomplete image sets to the findings on standard eye examination. RESULTS: The
      majority of image sets contained all 5 retinal images (92.8%). The disk center
      view was the image most likely to be present and to be of acceptable image
      quality (96.8%). The nasal retina was the most difficult to obtain with
      acceptable image quality (83.4%). Sensitivity of detection of RW-ROP was 82.1%
      when 5 retinal images of acceptable quality were submitted for grading, 67.2%
      when 4 acceptable images were submitted, and 66.7% for 3 or fewer acceptable
      images (P = 0.02), with corresponding specificity of 82.2%, 89.0%, and 81.7%
      respectively (P < 0.0001). When images of any quality were evaluated, sensitivity
      was not increased (P = 0.74). CONCLUSIONS: The likelihood of detecting RW-ROP by
      telemedicine screening is decreased when a full set of retinal images is not
      obtained.

PMID- 27702610
TI  - Multi-template analysis of human perirhinal cortex in brain MRI: Explicitly
      accounting for anatomical variability.
AB  - RATIONAL: The human perirhinal cortex (PRC) plays critical roles in episodic and
      semantic memory and visual perception. The PRC consists of Brodmann areas 35 and
      36 (BA35, BA36). In Alzheimer's disease (AD), BA35 is the first cortical site
      affected by neurofibrillary tangle pathology, which is closely linked to neural
      injury in AD. Large anatomical variability, manifested in the form of different
      cortical folding and branching patterns, makes it difficult to segment the PRC in
      MRI scans. Pathology studies have found that in ~97% of specimens, the PRC falls
      into one of three discrete anatomical variants. However, current methods for PRC
      segmentation and morphometry in MRI are based on single-template approaches,
      which may not be able to accurately model these discrete variants METHODS: A
      multi-template analysis pipeline that explicitly accounts for anatomical
      variability is used to automatically label the PRC and measure its thickness in
      T2-weighted MRI scans. The pipeline uses multi-atlas segmentation to
      automatically label medial temporal lobe cortices including entorhinal cortex,
      PRC and the parahippocampal cortex. Pairwise registration between label maps and
      clustering based on residual dissimilarity after registration are used to
      construct separate templates for the anatomical variants of the PRC. An optimal
      path of deformations linking these templates is used to establish correspondences
      between all the subjects. Experimental evaluation focuses on the ability of
      single-template and multi-template analyses to detect differences in the
      thickness of medial temporal lobe cortices between patients with amnestic mild
      cognitive impairment (aMCI, n=41) and age-matched controls (n=44). RESULTS: The
      proposed technique is able to generate templates that recover the three dominant
      discrete variants of PRC and establish more meaningful correspondences between
      subjects than a single-template approach. The largest reduction in thickness
      associated with aMCI, in absolute terms, was found in left BA35 using both
      regional and summary thickness measures. Further, statistical maps of regional
      thickness difference between aMCI and controls revealed different patterns for
      the three anatomical variants.

PMID- 27702613
TI  - Insights in human epigenomic dynamics through comparative primate analysis.
AB  - Epigenomic analysis gives a molecular insight into cell-specific genomic
      activity. It provides a detailed functional plan to dissect an organism, tissue
      by tissue. Therefore comparative epigenomics may increase understanding of human
      acquired traits, by revealing regulatory changes in systems such as the
      neurological, musculoskeletal, and immunological. Enhancer loci evolve fast by
      hijacking elements from other tissues or rewiring and amplifying existing units
      for human-specific function. Promoters by contrast often require a CpG dense
      genetic infrastructure. Specific interplay occurs between the two, but also a
      shared modality of function, with coordination from global chromatin-modifying
      enzymes. Changes in specific transcription factor binding sites also facilitate
      the local epigenetic state. In the case of CTCF, these may further influence 3
      dimensional structure and interaction. How these mechanistic units are modulated
      between tissue and species enables more comprehensive understanding of human
      processes and pathology. With this information, precise therapeutic targeting of
      these epigenetic modifications may become possible.

PMID- 27702614
TI  - Streamlined structure elucidation of an unknown compound in a pigment
      formulation.
AB  - A fast and reliable quality control is important for ink manufacturers to ensure
      a constant production grade of mixtures and chemical formulations, and unknown
      components attract their attention. Structure elucidating techniques seem time
      consuming in combination with column-based methods, but especially the low
      solubility of pigment formulations is challenging the analysis. In contrast,
      layer chromatography is more tolerant with regard to pigment particles. One PLC
      plate for NMR and FTIR analyses and one HPTLC plate for recording of high
      resolution mass spectra, MS/MS spectra and for gathering information on polarity
      and spectral properties were needed to characterize a structure, exemplarily
      shown for an unknown component in pigment Red 57:1 to be 3-hydroxy-2-naphtoic
      acid. A preparative layer chromatography (PLC) workflow was developed that used
      an Automated Multiple Development 2 (AMD 2) system. The 0.5-mm PLC plate could
      still be operated in the AMD 2 system and allowed a smooth switch from the
      analytical to the preparative gradient separation. Through automated gradient
      development and the resulting focusing of bands, the sharpness of the PLC bands
      was improved. For NMR, the necessary high load of the target compound on the PLC
      plate was achieved via a selective solvent extraction that discriminated the
      polar sample matrix and thus increased the application volume of the extract that
      could maximally be applied without overloading. By doing so, the yield for NMR
      analysis was improved by a factor of 9. The effectivity gain through a simple,
      but thoroughly chosen extraction solvent is often overlooked, and for educational
      purpose, it was clearly illustrated and demonstrated by an extended solvent
      screening. Thus, PLC using an automated gradient development after a selective
      extraction was proven to be a new powerful combination for structural elucidation
      by NMR.

PMID- 27702616
TI  - Internal standards for use in the comprehensive analysis of polychlorinated
      aromatic hydrocarbons using gas chromatography combined with multiphoton
      ionization mass spectrometry.
AB  - To decrease health-risks to humans, non-toxic compounds were evaluated for use as
      internal standards for calibrating data obtained by gas
      chromatography/multiphoton ionization mass spectrometry (GC-MPI-MS) using an
      ultraviolet femtosecond laser as the ionization source. The retention time in the
      mass chromatogram was calibrated using a retention index, in which a series of n
      alkanes was employed as internal standards for evaluating the retention times for
      polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
      and polychlorinated biphenyls (PCBs). To compensate for changes in signal
      intensity in MPI-MS, the dependence of signal intensity on the laser pulse energy
      was investigated for the dioxin-like compounds, in addition to five non-toxic
      aromatic hydrocarbons, that were used as internal standards. Based on their
      similar behavior,the non-toxic PCDD/PCDF, its 13C-isotope, and pentachlorobenzene
      behave similarly, we conclude that they can be used for calibrating the signal
      intensities in MPI-MS.

PMID- 27702615
TI  - Development of a 45kpsi ultrahigh pressure liquid chromatography instrument for
      gradient separations of peptides using long microcapillary columns and sub-2MUm
      particles.
AB  - Commercial chromatographic instrumentation for bottom-up proteomics is often
      inadequate to resolve the number of peptides in many samples. This has inspired a
      number of complex approaches to increase peak capacity, including various
      multidimensional approaches, and reliance on advancements in mass spectrometry.
      One-dimensional reversed phase separations are limited by the pressure
      capabilities of commercial instruments and prevent the realization of greater
      separation power in terms of speed and resolution inherent to smaller sorbents
      and ultrahigh pressure liquid chromatography. Many applications with complex
      samples could benefit from the increased separation performance of long capillary
      columns packed with sub-2MUm sorbents. Here, we introduce a system that operates
      at a constant pressure and is capable of separations at pressures up to 45kpsi.
      The system consists of a commercially available capillary liquid chromatography
      instrument, for sample management and gradient creation, and is modified with a
      storage loop and isolated pneumatic amplifier pump for elevated separation
      pressure. The system's performance is assessed with a complex peptide mixture and
      a range of microcapillary columns packed with sub-2MUm C18 particles.

PMID- 27702617
TI  - A solid-phase microextraction coating of sol-gel-derived perhydroxy
      cucurbit[6]uril and its application on to the determination of polycyclic
      aromatic hydrocarbon.
AB  - A novel solid-phase microextraction coating that contains perhydroxy
      cucurbit[6]uril((OH)12Q[6]) was prepared by a sol-gel method. (OH)12Q[6] was used
      as a starting coating material with hydroxy-terminated poly(dimethylsiloxane) (OH
      PDMS) to bond chemically to a fused-silica substrate using 3-(2
      cyclooxypropoxyl)propyltrimethoxysilane as cross-linking agent; hydrolysis and
      polycondensation reactions then led to the formation of a (OH)12Q[6]/PDMS
      coating. The coating has a high thermal stability (360 degrees C), long lifetime
      and can withstand organic and inorganic solvent rinsing because of the chemical
      binding between the coating and silica substrate. Its performance was tested by
      headspace (HS) solid-phase microextraction fiber coupled with gas chromatography
      to determine polycyclic aromatic hydrocarbon (PAHs) compounds in water samples.
      The (OH)12Q[6]/PDMS-coated fiber exhibited higher enrichment factors from
      fourfold for naphthalene to tenfold for pyrene compared with commercial PDMS
      fiber, and the enrichment factors increased with the number of condensed PAH
      rings. The strong adsorption affinity is believed to be attributed to hydrogen
      bonding and CH?pi interactions between PAHs and (OH)12Q[6], according to the
      results of quantum chemical calculations. In the PAH analysis, the (OH)12Q[6]
      coated fiber showed a good repeatability (<4.7%) and reproducibility between
      fibers (<9.4%), low detection limits (0.03-0.15MUgL-1), and a wide linearity (0.1
      1000MUgL-1) under optimized conditions. This method was used for the simultaneous
      determination of seven PAHs with satisfactory recoveries of 90.56%-107.4% for
      Huaxi river water samples and 90.23%-109.5% for local wastewater samples,
      respectively.

PMID- 27702618
TI  - Detecting cognitive changes in preclinical Alzheimer's disease: A review of its
      feasibility.
AB  - Significant progress has been made in characterizing the biological changes
      occurring in preclinical Alzheimer's disease (AD). Cognitive dysfunction has been
      viewed, however, as a late-stage phenomenon, despite increasing evidence that
      changes may be detected in the decades preceding dementia. In the absence of
      comprehensive evidence-based guidelines for preclinical cognitive assessment,
      longitudinal cohort and neuroimaging studies have been reviewed to determine the
      temporal order and brain biomarker correlates of specific cognitive functions.
      Episodic memory decline was observed to be the most salient cognitive function,
      correlating with high levels of amyloid deposition and hypoconnectivity across
      large-scale brain networks. Prospective studies point to early decline in both
      episodic and semantic memory processing as well as executive functions in the
      predementia period. The cognitive tests have, however, been principally those
      used to diagnose dementia. New procedures are required which target more finely
      the medial temporal lobe subregions first affected by clinically silent AD
      pathology.

PMID- 27702619
TI  - Recommended cognitive outcomes in preclinical Alzheimer's disease: Consensus
      statement from the European Prevention of Alzheimer's Dementia project.
AB  - The Horizon 2020/IMI European Prevention of Alzheimer's Dementia (EPAD) project
      will undertake large-scale proof-of-concept trials in predementia Alzheimer's
      disease (AD). Within EPAD, the monitoring of cognitive trajectories in the
      preclinical period will constitute a central outcome measure; however, there are
      currently no clear guidelines as to how this should be achieved as most measures
      have been developed for the period around dementia diagnosis. The EPAD Scientific
      Advisory Group for Clinical and Cognitive Outcomes identified appropriate
      cognitive measures based on a literature search covering both cognitive
      correlates of preclinical brain changes from imaging studies and cognitive
      changes observed over time in nondementia population cohorts developing incident
      dementia. These measures were evaluated according to the following criteria:
      validity, coherence with biomarker changes, psychometric properties, cross
      cultural suitability, availability of alternative forms, and normative data
      limited practice effects. The resulting consensus statement provides
      recommendations for both future drug trials and research into preclinical
      Alzheimer's disease.

PMID- 27702620
TI  - Trends in Prevalence of Diagnosed Ocular Disease and Utilization of Eye Care
      Services in American Veterans.
AB  - PURPOSE: To assess trends in prevalence of diagnosed ocular disease and use of
      eye care services in the Veterans Affairs (VA) health care system. DESIGN:
      Prevalence study. METHODS: We performed a retrospective study of all eligible
      veterans in the VA Capitol Health Care Network from 2007 to 2011. The VA database
      was used to abstract demographic and socioeconomic variables, including age,
      race, sex, marital status, service connection, prescription copay, homelessness,
      and VA facility. Primary outcome measures were the prevalence of diagnosed ocular
      disease and use of eye care. Ocular diagnoses were determined by International
      Classification of Diseases, 9th revision codes and use by prescription medication
      fills, visits to eye care clinics, and cataract surgery frequency. RESULTS: The
      average age of veterans ranged from 59.8-60.9, most veterans were male (88.1
      89.8%), and there was a high proportion of African Americans (29.5-30%). The
      prevalence of all ocular diagnoses increased from 20.5% in 2007 to 23.3% in 2011
      (P < .01), a 13.7% increase. Similarly, the prevalence of diagnosed cataract
      increased by 35.7% (P = .02) from 7.1% in 2007 to 9.6% in 2011. Diagnosed
      glaucoma prevalence increased by 9.4% (P = .03) from 6.7 to 7.4%. The percent of
      patients seen in eye clinics increased 11.6%% in the 5-year study period to 24.0%
      in fiscal year 2011 (P = .05). The use of ophthalmic medications increased 20% (P
      < .01). The rate of cataract surgery did not change significantly during the
      study period. CONCLUSIONS: The prevalence of diagnosed eye conditions among
      American Veterans is increasing, as is the use of eye care services. Cataract
      surgery rates did not increase, which may indicate a need to increase
      availability of these services.

PMID- 27702621
TI  - Relationships Between Anthropometric Measurements and Intraocular Pressure: The
      Korea National Health and Nutrition Examination Survey.
AB  - PURPOSE: To evaluate the relationship between intraocular pressure (IOP) and
      various anthropometric measures. DESIGN: A population-based cross-sectional
      study. METHODS: A total of 5008 participants, 2080 men and 2928 women >=19 years
      of age were included from the Korea National Health and Nutrition Examination
      Survey V database, focusing on the years 2010 and 2011. We selected IOP in the
      right eye of a normal healthy population as the outcome variable of our study. We
      analyzed the relationship between IOP and anthropometric parameters using dual
      energy X-ray absorptiometry by sex. Lean body mass was calculated as total body
      mass minus fat mass. We used general linear models and logistic regression
      analysis to evaluate risk factors of high IOP. Our main outcome measure was
      correlation between anthropometric data and IOP. RESULTS: In multivariate general
      linear models, greater body mass index (BMI) and waist circumference were
      correlated with higher IOP for both men (BMI, beta = 0.053, P = .026; waist
      circumference, beta = 0.016, P = .067) and women (BMI, beta = 0.074, P < .001;
      waist circumference, beta = 0.028, P < .001). Greater fat mass (beta = 0.027, P =
      .037) and fat mass/lean body mass (beta = 1.170, P = .06) were correlated with
      higher IOP, while greater lean body mass/weight (beta = -3.188, P = .025), lean
      body mass/BMI (beta = -1.379, P = .002), appendicular skeletal muscle mass/BMI
      (beta = -2.270, P = .022), and bone mineral content/BMI (beta = -11.653, P =
      .031) were correlated with lower IOP in women, but not in men (P > .10).
      CONCLUSIONS: In healthy women, greater fat mass was associated with higher IOP,
      and greater muscle mass was associated with lower IOP after adjusting for weight
      and BMI. Fat and muscle influenced IOP in women independently.

PMID- 27702622
TI  - Intraoperative Interface Fluid Dynamics and Clinical Outcomes for Intraoperative
      Optical Coherence Tomography-Assisted Descemet Stripping Automated Endothelial
      Keratoplasty From the PIONEER Study.
AB  - PURPOSE: To correlate intraoperative interface fluid dynamics during Descemet
      stripping automated endothelial keratoplasty (DSAEK) using intraoperative optical
      coherence tomography (iOCT) in the Prospective Intraoperative and Perioperative
      Ophthalmic Imaging with Optical Coherence Tomography (PIONEER) study with
      postoperative outcomes. DESIGN: Prospective consecutive, interventional,
      comparative case series. PARTICIPANTS: One hundred seventy-eight eyes of 173
      patients undergoing DSAEK from the Cole Eye Institute, Cleveland, Ohio. METHODS:
      Eyes that underwent DSAEK between October 2011 and March 2014 from the PIONEER
      intraoperative and perioperative OCT study were included. An automated interface
      fluid segmentation algorithm evaluated intraoperative dynamics of interface fluid
      before and after surgical manipulations. iOCT images were also captured at
      multiple intraoperative time points for 2 different DSAEK techniques, 1 that used
      an active air infusion system and 1 that did not. MAIN OUTCOME MEASURES:
      Interface fluid metrics, graft nonadherence. RESULTS: iOCT measurements of
      interface fluid after final surgical manipulations and immediately before leaving
      the operating room identified that total fluid volume (P = .002), largest fluid
      volume pocket (P = .002), max fluid area (P = .006), mean fluid thickness (P =
      .03), and max fluid thickness (P = .01) significantly correlated with graft
      nonadherence rates within the first postoperative week. After placement and
      optimization of intraoperative lenticle adherence, iOCT revealed a significant
      difference between the area, volume, and thickness of maximum fluid pockets
      between the 2 surgical techniques, but both techniques resulted in significant
      reduction of interface fluid during the procedure. CONCLUSIONS: Larger residual
      interface fluid volume, area, and thickness at the end of surgery detected with
      iOCT are associated with early graft nonadherence and can be quantified with an
      automated algorithm. iOCT imaging can successfully capture technique-dependent
      differences in fluid dynamics during DSAEK.

PMID- 27702623
TI  - Changes in Ocular Parameters and Intraocular Lens Powers in Aging Cycloplegic
      Eyes.
AB  - PURPOSE: Age-related changes in lens elasticity and ciliary muscle contractility
      can affect how ocular parameters respond to cycloplegia, and therefore
      intraocular lens (IOL) power measurements calculated by formulas using anterior
      chamber depth (ACD), lens thickness (LT), or white-to-white (WtW) for effective
      lens position prediction can vary. In response, using swept-source optical
      biometry in prepresbyopic and presbyopic eyes, we investigated changes in ocular
      parameters and IOL power calculations attributable to cycloplegia. DESIGN: Cross
      sectional study. METHODS: In 38 prepresbyopic and 42 presbyopic eyes, we measured
      pupil diameter, radius of corneal curvature values, central corneal thickness,
      WtW, ACD, LT, and axial length both before and after cycloplegia. We determined
      IOL power calculations with the Sanders-Retzlaff-Kraff/theoretical, Holladay 2,
      and Haigis formulas. To pinpoint the effect of cycloplegia, we recorded
      refractive predictions in pre- and postdilation conditions according to the same
      IOL power calculations, even if postdilation IOL power calculations had changed.
      RESULTS: With cycloplegia, pupil diameter changed significantly more in
      presbyopic eyes (P < .001). Central corneal thickness decreased in prepresbyopic
      eyes (P = .048), whereas WtW increased in presbyopic eyes (P = .02). In both
      groups, ACD and LT changed significantly (P < .001). IOL power calculations
      according to the Holladay 2 formula differed in prepresbyopic eyes (P = .042),
      and refractive predictions with the Holladay 2 and Haigis formulas differed
      significantly in prepresbyopic eyes (P = .043 and P = .022, respectively).
      CONCLUSION: Surgeons should consider the effect of cycloplegia on refractive
      prediction errors and IOL power calculations determined with Haigis and Holladay
      2 formulas, especially in prepresbyopic ages.

PMID- 27702624
TI  - Outcomes With As-Needed Aflibercept and Macular Laser Following the Phase III
      VISTA DME Trial: ENDURANCE 12-Month Extension Study.
AB  - PURPOSE: To determine whether the efficacy and safety achieved with 2.0 mg
      intravitreal aflibercept injections (IAIs) for diabetic macular edema (DME)
      during the phase III VISTA DME trial were maintained with individualized, as
      needed treatment. DESIGN: Phase IV, multicenter, open-label extension study.
      METHODS: Sixty patients completing VISTA DME elected to enter the ENDURANCE
      extension study. All patients received IAIs in the presence of clinically
      relevant DME. Patients were observed at 4-, 8-, or 12-week intervals depending on
      the need for treatment. Main outcome measures were mean IAIs given through month
      12 (M12), the proportion of patients receiving no IAIs, and the role of macular
      laser in decreasing treatment burden among patients requiring ongoing IAIs.
      RESULTS: A mean of 4.5 IAIs were administered through M12. Eighteen (30%)
      patients required no IAIs, and among those who met IAI retreatment criteria, a
      mean of 6.0 IAIs were administered through M12. Best-corrected visual acuity
      gains achieved during VISTA DME were maintained and stable with individualized
      dosing during ENDURANCE, fluctuating by <1.5 mean letters from the baseline at
      all time points. Likewise, mean central retinal thickness remained relatively
      stable during ENDURANCE. Thirty-seven (62%) patients met macular laser criteria
      at a mean of 19.5 weeks with no significant difference in the frequency of IAIs
      before or after macular laser. CONCLUSION: Vision gains achieved during the 3
      year VISTA DME trial were maintained through M12 of the ENDURANCE extension study
      with a reduced treatment frequency, with 30% of patients receiving no IAIs. No
      significant reduction in IAI frequency was observed after macular laser
      application.

PMID- 27702625
TI  - Metformin, beyond an insulin sensitizer, targeting heart and pancreatic beta
      cells.
AB  - Metformin, a biguanide derivate, is known as the first-line antidiabetic agent
      for type 2 diabetes mellitus (T2DM) treatment. It reduces insulin resistance and
      decreases blood glucose concentration by inhibiting gluconeogenesis and
      suppressing hepatic glucose production with improved peripheral tissue insulin
      sensitivity. As an insulin sensitizer, metformin takes pleiotropic actions and
      exerts protective effects on multiple organs mainly in insulin-targeted tissues
      such as liver, muscle, and adipose tissues. Recent studies discover that
      metformin also plays essential roles in heart and pancreatic beta cells - two
      important organs in metabolic regulation. Metformin not only protects T2DM
      patients from cardiovascular diseases and heart failure, but also restores
      insulin secretion activities and protects pancreatic beta cells from lipotoxicity
      or glucotoxicity. Although accumulated evidence shed light on the metformin
      action, the precise mechanism of metformin is still under investigation. Further
      laboratory investigations and clinical trials are needed to pinpoint a map of
      metformin action. Based on recent findings, this review characterizes the
      beneficial role of metformin in cardiovascular diseases and pancreatic beta
      cells.

PMID- 27702627
TI  - Combined damage produced by multiple mild cerebral insults assessed using MRI in
      neonatal rats.
AB  - PURPOSE: To determine whether damage to neonatal brain is exacerbated with
      multiple mild cerebral insults as detected with MRI and corroborated using
      histology. MATERIALS AND METHODS: The combined brain injury produced by multiple
      procedures was compared in neonatal rats having: Sham surgery at P5, Sham surgery
      at P5 plus a diffuse mild transient unilateral cerebral hypoxia ischemia (HI) at
      P7, HI alone, and a minor photothrombotic (PT) stroke at P5 followed by HI. MRI
      after the ischemic insults was followed by final histology. RESULTS: PT produced
      lesions with increased T2 and decreased apparent diffusion coefficient for water
      (ADC) but no significant effects of a second HI. However, near the PT
      lesion/parietal cortex there were patchy areas of enhanced T2 and decreased ADC
      in 6/9, 3/8 and 0/8 animals in the PT+HI, Sham+HI and HI groups, respectively
      (P<0.05). Patches corresponded histologically to increased vacuolation and cell
      death and were more pronounced in the PT+HI and Sham+PT groups than the HI group.
      CONCLUSION: The extent of damage produced by a minor neonatal stroke followed by
      a diffuse HI two days later results in heterogeneous enhancement of T2, ADC and
      histological injury near the lesion. Surgical procedures including mechanical
      head manipulation followed by HI also produced some enhanced heterogeneity of
      hypoxic-ischemic injury affirming the need for sham controls.

PMID- 27702626
TI  - Parkin elimination of mitochondria is important for maintenance of lens
      epithelial cell ROS levels and survival upon oxidative stress exposure.
AB  - Age-related cataract is associated with oxidative stress and death of lens
      epithelial cells (LECs) whose survival is dependent on functional mitochondrial
      populations. Oxidative stress-induced depolarization/damage of LEC mitochondria
      results in increased reactive oxygen species (ROS) levels and cell death
      suggesting the need for a LEC mechanism to remove mitochondria
      depolarized/damaged upon oxidative stress exposure to prevent ROS release and LEC
      death. To date, a mechanism(s) for removal of depolarized/damaged LEC
      mitochondria has yet to be identified and the importance of eliminating oxidative
      stress-damaged mitochondria to prevent LEC ROS release and death has not been
      established. Here, we demonstrate that Parkin levels increase in LECs exposed to
      H2O2-oxidative stress. We establish that Parkin translocates to LEC mitochondria
      depolarized upon oxidative stress exposure and that Parkin recruits p62/SQSTM1 to
      depolarized LEC mitochondria. We demonstrate that translocation of Parkin results
      in the elimination of depolarized/damaged mitochondria and that Parkin clearance
      of LEC mitochondria is dependent on its ubiquitin ligase activity. Importantly,
      we demonstrate that Parkin elimination of damaged LEC mitochondria results in
      reduced ROS levels and increased survival upon oxidative stress exposure. These
      results establish that Parkin functions to eliminate LEC mitochondria
      depolarized/damaged upon oxidative stress exposure and that elimination of
      damaged mitochondria by Parkin is important for LEC homeostasis and survival. The
      data also suggest that mitochondrial quality control by Parkin could play a role
      in lens transparency.

PMID- 27702628
TI  - Effects of repeated high-dose methamphetamine and ceftriaxone post-treatments on
      tissue content of dopamine and serotonin as well as glutamate and glutamine.
AB  - Repeated exposure to high doses of methamphetamine (METH) is known to alter
      several neurotransmitters in certain brain regions. Little is known about the
      effects of ceftriaxone (CEF), a beta-lactam antibiotic, known to upregulate
      glutamate transporter subtype 1, post-treatment on METH-induced depletion of
      dopamine and serotonin (5-HT) tissue content in brain reward regions. Moreover,
      the effects of METH and CEF post-treatment on glutamate and glutamine tissue
      content are not well understood. In this study, Wistar rats were used to
      investigate the effects of METH and CEF post-treatment on tissue content of
      dopamine/5-HT and glutamate/glutamine in the nucleus accumbens (NAc) and
      prefrontal cortex (PFC). Rats received either saline or METH (10mg/kg, i.p. every
      2h*4) followed by either saline or CEF (200mg/kg, i.p, every day*3) post
      treatment. METH induced a significant depletion of dopamine and 5-HT in the NAc
      and PFC. Importantly, dopamine tissue content was completely restored in the NAc
      following CEF post-treatment. Additionally, METH caused a significant decrease in
      glutamate and glutamine tissue content in PFC, and this effect was attenuated by
      CEF post-treatment. These findings demonstrate for the first time the attenuating
      effects of CEF post-treatment on METH induced alterations in the tissue contents
      of dopamine, glutamate, and glutamine.

PMID- 27702629
TI  - Extracellular matrix components as therapeutics for spinal cord injury.
AB  - There is no treatment for people with spinal cord injury that leads to
      significant functional improvements. The extracellular matrix is an intricate, 3
      dimensional, structural framework that defines the environment for cells in the
      central nervous system. The components of extracellular matrix have signaling and
      regulatory roles in the fate and function of neuronal and non-neuronal cells in
      the central nervous system. This review discusses the therapeutic potential of
      extracellular matrix components for spinal cord repair.

PMID- 27702630
TI  - The Exact Mechanism by Which Hepatic Transmembrane 6 Superfamily Member 2
      Modulates Triglyceride Metabolism Is Still Uncertain.

PMID- 27702631
TI  - Oral Contraceptive Use and Crohn's Disease Complications.

PMID- 27702632
TI  - Did Statins Really Improve Survival in Cirrhotic Patients With a History of
      Variceal Bleeding?

PMID- 27702633
TI  - Is Early Endoscopy-Based Therapy the Best Strategy to Prevent All Crohn's Disease
      Postoperative Recurrence?

PMID- 27702634
TI  - Prefrontal cortical activity associated with visual stimulus categorization in
      non-human primates measured with near-infrared spectroscopy.
AB  - In biomedical research of brain dysfunction in psychiatric disorders, utilization
      of animal models is essential. However, translation of findings in animal models
      into the realm of human clinical conditions requires reliable biomarkers that are
      assessed with the methods mutually employed in animal models and human patients.
      Near-infrared spectroscopy (NIRS) is a functional neuroimaging technique that has
      now been widely utilized in human basic and clinical research. However, its
      application to animal models has been barely conducted. In this study, we
      developed the method to measure neural activity in the cortex of Japanese
      macaques using NIRS, and examined cortical responses to presentation of a set of
      visual stimuli that were categorized into four different groups (flower, monkey,
      snake, food). Prefrontal cortical (PFC) oxy- and deoxy-hemoglobin changes were
      found to reliably distinguish the categories of these visual stimuli. The results
      suggest that cortical activity measurement with NIRS in primates can be a
      valuable model for identifying biomarkers associated with psychiatric disorders.

PMID- 27702635
TI  - Physical exercise induces hippocampal neurogenesis and prevents cognitive
      decline.
AB  - Accumulating evidence from animal and human research indicate that adult
      hippocampal neurogenesis plays a key role in cognition. Meanwhile, cognitive
      decline is well known to associate with ageing-related neurodegenerative diseases
      such as Alzheimer's disease (AD) and Parkinson's disease (PD). Therefore,
      prevention of hippocampal neurogenesis reduction should be critical for these
      diseases. Physical exercise, a potent enhancer of adult hippocampal neurogenesis,
      has emerged as a potential therapy or an adjunctive therapeutic strategy for
      cognitive decline. In this review, we discuss the recent findings on hippocampal
      neurogenesis and the incorporation of new born neurons into the neuronal network
      in humans and in rodents. By focusing on hippocampal neurogenesis, we illustrate
      the role and possible mechanisms of physical exercise in cognition preservation.

PMID- 27702636
TI  - Intracranial self-stimulation also facilitates learning in a visual
      discrimination task in the Morris water maze in rats.
AB  - Intracranial self-Stimulation (ICSS) of the medial forebrain bundle is a
      treatment capable of consistently facilitating acquisition of learning and memory
      in a wide array of experimental paradigms in rats. However, the evidence
      supporting this effect on implicit memory comes mainly from classical
      conditioning and avoidance tasks. The present work aims to determine whether ICSS
      would also improve the performance of rats in another type of implicit task such
      as cued simultaneous visual discrimination in the Morris Water Maze. The ICSS
      treatment was administered immediately after each of the five acquisition
      sessions and its effects on retention and reversal were evaluated 72h later.
      Results showed that ICSS subjects committed fewer errors than Sham subjects and
      adopted more accurate trajectories during the acquisition of the task. This
      improvement was maintained until the probe test at 72h. However, ICSS animals
      experienced more difficulties than the Sham group during the reversal of the same
      learning, reflecting an impairment in cognitive flexibility. We conclude that
      post-training ICSS could also be an effective treatment for improving implicit
      visual discrimination learning and memory.

PMID- 27702637
TI  - Aging process alters hippocampal and cortical secretase activities of Wistar
      rats.
AB  - A growing body of evidence has demonstrated amyloid plaques in aged brain;
      however, little attention has been given to amyloid precursor protein (APP)
      processing machinery during the healthy aging process. The amyloidogenic and non
      amyloidogenic pathways, represented respectively by beta- and alpha-secretases
      (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that
      the normal aging process could imbalance amyloidogenic and non-amyloidogenic
      pathways specifically BACE and TACE activities. Besides, although it has been
      showed that exercise can modulate secretase activities in Alzheimer Disease
      models the relationship between exercise effects and APP processing during
      healthy aging process is rarely studied. Our aim was to investigate the aging
      process and the exercise effects on cortical and hippocampal BACE and TACE
      activities and aversive memory performance. Young adult and aged Wistar rats were
      subjected to an exercise protocol (20min/day for 2 weeks) and to inhibitory
      avoidance task. Biochemical parameters were evaluated 1h and 18h after the last
      exercise session in order to verify transitory and delayed exercise effects. Aged
      rats exhibited impaired aversive memory and diminished cortical TACE activity.
      Moreover, an imbalance between TACE and BACE activities in favor of BACE activity
      was observed in aged brain. Moderate treadmill exercise was unable to alter
      secretase activities in any brain areas or time points evaluated. Our results
      suggest that aging-related aversive memory decline is partly linked to decreased
      cortical TACE activity. Additionally, an imbalance between secretase activities
      can be related to the higher vulnerability to neurodegenerative diseases induced
      by aging.

PMID- 27702638
TI  - Application of various control strategies to Japanese encephalitic: A
      mathematical study with human, pig and mosquito.
AB  - Japanese encephalitis (JE) is a public health problem that threats the entire
      world today. Japanese Encephalitis virus (JEV) mostly became a threat due to the
      significant number of increase of susceptible mosquito vectors and vertebrate
      hosts in Asia by which around 70,000 cases and 10,000 deaths per year took place
      in children below 15 years of age. In this paper, a mathematical model of JE due
      to JEV from the vector source (infected mosquito) and two vertebrate hosts
      (infected human and infected pig) is formulated. The disease can be controlled by
      applying several control measures such as vaccination, medicine and insecticide
      to the JE infection causing species. The model has been formulated as an optimal
      control problem and has been solved using Pontryagin's maximum principle. Also,
      the stability of the system has been studied with the help of basic reproduction
      number for disease free and endemic equilibrium. The results of fixed control for
      endemic equilibrium is presented numerically and depicted graphically. The
      effects of different control strategies on human, pig and mosquito has been
      analyzed using Runge-Kutta 4th order forward and backward techniques and
      presented thereafter graphically.

PMID- 27702640
TI  - Cell-specific functions of miRNA in the liver.

PMID- 27702639
TI  - The influence of walkability on broader mobility for Canadian middle aged and
      older adults: An examination of Walk ScoreTM and the Mobility Over Varied
      Environments Scale (MOVES).
AB  - Neighborhood built environments may play an important role in shaping mobility
      and subsequent health outcomes. However, little work includes broader mobility
      considerations such as cognitive ability to be mobile, social connections with
      community, or transportation choices. We used a population-based sample of
      Canadian middle aged and older adults (aged 45 and older) from the Canadian
      Community Health Survey-Healthy Aging (CCHS-HA, 2008-2009) to create a holistic
      mobility measure: Mobility over Varied Environments Scale (MOVES). Data from CCHS
      HA respondents from British Columbia with MOVES were linked with Street Smart
      Walk ScoreTM data by postal code (n=2046). Mean MOVES was estimated across
      sociodemographic and health characteristics. Linear regression, adjusted for
      relevant covariates, was used to estimate the association between Street Smart
      Walk ScoreTM and the MOVES. The mean MOVES was 30.67 (95% confidence interval
      (CI) 30.36, 30.99), 5th percentile 23.27 (CI 22.16, 24.38) and 95th percentile
      was 36.93 (CI 35.98, 37.87). MOVES was higher for those who were younger,
      married, higher socioeconomic status, and had better health. In unadjusted
      models, for every 10 point increase in Street Smart Walk ScoreTM, MOVES increased
      4.84 points (CI 4.52, 5.15). However, results attenuated after adjustment for
      sociodemographic covariates: each 10 point increase in Street Smart Walk ScoreTM
      was associated with a 0.10 (CI 0.00, 0.20) point increase in MOVES. The modest
      but important link we observed between walkability and mobility highlights the
      implication of neighborhood design on the health of middle aged and older adults.

PMID- 27702641
TI  - Sofosbuvir shows antiviral activity in a patient with chronic hepatitis E virus
      infection.

PMID- 27702642
TI  - Bad memories from the gut may cause nightmares for the bile ducts.

PMID- 27702643
TI  - Electroencephalographic correlates of states of concentrative meditation.
AB  - Meditative techniques aim for and meditators report states of mental alertness
      and focus, concurrent with physical and emotional calm. We aimed to determine the
      electroencephalographic (EEG) correlates of five states of Buddhist concentrative
      meditation, particularly addressing a correlation with meditative level. We
      studied 12 meditators and 12 pair-matched meditation-naive participants using
      high-resolution scalp-recorded EEG. To maximise reduction of EMG, data were pre
      processed using independent component analysis and surface Laplacian transformed
      data. Two non-meditative and five meditative states were used: resting baseline,
      mind-wandering, absorptions 1, 2, 3, 4 and 5 (corresponding to four levels of
      absorption and an absorption with a different object of focus, otherwise
      equivalent to level 4; these five meditative states produce repeatable,
      distinctly different experiences for experienced meditators). The experimental
      protocol required participants to experience the states in the order listed
      above, followed immediately by the reverse. We then calculated EEG power in
      standard frequency bands from 1 to 80Hz. We observed decreases of central scalp
      beta (13-25Hz), and central low gamma (25-48Hz) power in meditators during deeper
      absorptions. In contrast, we identified increases in frontal midline and temporo
      parietal theta power in meditators, again, during deeper absorptions. Alpha
      activity was increased over all meditative states, not depth-related. This study
      demonstrates that the subjective experiences of deepening meditation partially
      correspond to measures of EEG. Our results are in accord with prior studies on
      non-graded meditative states. These results are also consistent with increased
      theta correlating with tightness of focus, and reduced beta/gamma with the
      desynchronization associated with enhanced alertness.

PMID- 27702644
TI  - Making sense of what you sense: Disentangling interoceptive awareness,
      sensibility and accuracy.
AB  - Garfinkel and Critchley (2013) recently proposed a three level model of
      interoception. Only few studies, however, have empirically tested this
      theoretical model thus far. The present study aimed at investigating (1) the
      central assumptions of this model, i.e. that Accuracy, Sensibility and Awareness
      are distinguishable facets of interoception and that Interoceptive Accuracy is
      the basic level of interoception, and (2) whether cardiovascular activation (as
      indexed by heart rate) is differentially related to the three facets of
      interoception. Analyses were conducted on a total sample of N=159 healthy
      participants (118 female [74.2%]; mean age=23.9years, SD=3.3, range=19-45) who
      performed either the heartbeat tracking task, the heartbeat discrimination task
      or both. The results suggest that Accuracy, Sensibility and Awareness are
      empirically distinct facets of interoception, showing no correlation when based
      on heartbeat tracking, but moderate correlations when based on heartbeat
      discrimination. The assumption that Interoceptive Accuracy is the basic level of
      interoception could only be partially confirmed. Instead, we conclude that the
      level of objective physiological states should be considered as the most basic
      level of interoceptive signal processing.

PMID- 27702646
TI  - Sensory responses in the medial prefrontal cortex of anesthetized rats.
      Implications for sensory processing.
AB  - The medial prefrontal cortex (mPFC) plays a key role in higher functions such as
      memory and attention. In order to demonstrate sensory responses in the mPFC, we
      used electrophysiological recordings of urethane-anesthetized rats to record
      somatosensory-evoked potentials (SEPs) or auditory-evoked potentials (AEPs)
      elicited by whisker deflections and click stimulation, respectively.
      Contralateral whisker stimulation or auditory stimuli were also applied to study
      sensory interference in the mPFC. Interference with other sensory stimuli or
      recent stimulation history reduced whisker responses in the infralimbic and
      prelimbic cortices of the ventral mPFC. This effect could be mediated by
      activation of parvalbumin (PV) interneurons since the effect was blocked by the
      P/Q calcium channel antagonist omega-agatoxin. In contrast, sensory interference
      or the recent stimulation history was not detected by the dorsal mPFC or the
      primary somatosensory cortex. Results obtained from retrograde tracer injections
      in the dorsal and ventral regions of the mPFC indicated that somatosensory and
      auditory sensory inputs may arrive at the dorsal mPFC through secondary sensory
      cortical areas, and through the insular and temporal cortical areas. The ventral
      mPFC may receive sensory information through the strong anatomical connections
      between the dorsal and ventral mPFC areas. In conclusion, results suggest mPFC
      plays an important role in sensory processing, which may have important
      implications in attentional and memory processes.

PMID- 27702645
TI  - Timing of amphetamine exposure in relation to puberty onset determines its
      effects on anhedonia, exploratory behavior, and dopamine D1 receptor expression
      in young adulthood.
AB  - Non-medical use of amphetamine (AMPH) among adolescents is prevalent, which is
      problematic given the potential consequences of developmental drug exposure on
      brain function and behavior. Previously we found in adult male rats that AMPH
      exposure starting before puberty induces a persistent decrease in dopamine D1
      receptor (D1R) function in the medial prefrontal cortex (mPFC). Here we
      investigated if this dysfunction was associated with changes in D1R expression in
      the mPFC and nucleus accumbens (NAc). We also determined if starting drug
      exposure well before or near the onset of puberty would influence AMPH-induced
      changes in D1R expression and behavior. Male and female Sprague-Dawley rats were
      treated once every other day (10 injections total) with saline or 3mg/kg AMPH
      (i.p.) from either postnatal day (P) 27 to 45 (pre-puberty groups; Pre-P) or P37
      to 55 (peri-puberty groups; Peri-P). After 1, 7 and 21days of withdrawal, sucrose
      preference tests were performed to assess anhedonia. Exploratory behavior was
      studied in an open-field arena and on an elevated plus maze (EPM). Rats were then
      sacrificed for Western blot analysis of D1R expression. We found that AMPH
      withdrawal induced decreases in sucrose preference that persisted in rats with
      Peri-P onset treatment. Pre-P onset AMPH exposure led to increased open-arm
      exploration in the EPM test, as well as a decreased D1R level in the mPFC but not
      NAc. Our results demonstrated that AMPH exposure starting at different
      developmental stages resulted in distinct neurobehavioral abnormalities,
      suggesting an important role of exposure timing in drug-induced plasticity.

PMID- 27702648
TI  - Probing pain pathways with light.
AB  - We have witnessed an accelerated growth of photonics technologies in recent years
      to enable not only monitoring the activity of specific neurons, while animals are
      performing certain types of behavior, but also testing whether specific cells,
      circuits, and regions are sufficient or necessary for initiating, maintaining, or
      altering this or that behavior. Compared to other sensory systems, however, such
      as the visual or olfactory system, photonics applications in pain research are
      only beginning to emerge. One reason pain studies have lagged behind is that many
      of the techniques originally developed cannot be directly implemented to study
      key relay sites within pain pathways, such as the skin, dorsal root ganglia,
      spinal cord, and brainstem. This is due, in part, to difficulties in accessing
      these structures with light. Here we review a number of recent advances in design
      and delivery of light-sensitive molecular probes (sensors and actuators) into
      pain relay circuits to help decipher their structural and functional
      organization. We then discuss several challenges that have hampered hardware
      access to specific structures including light scattering, tissue movement and
      geometries. We review a number of strategies to circumvent these challenges, by
      delivering light into, and collecting it from the different key sites to unravel
      how nociceptive signals are encoded at each level of the neuraxis. We conclude
      with an outlook on novel imaging modalities for label-free chemical detection and
      opportunities for multimodal interrogation in vivo. While many challenges remain,
      these advances offer unprecedented opportunities to bridge cellular approaches
      with context-relevant behavioral testing, an essential step toward improving
      translation of basic research findings into clinical applications.

PMID- 27702647
TI  - Effect of acute lateral hemisection of the spinal cord on spinal neurons of
      postural networks.
AB  - In quadrupeds, acute lateral hemisection of the spinal cord (LHS) severely
      impairs postural functions, which recover over time. Postural limb reflexes
      (PLRs) represent a substantial component of postural corrections in intact
      animals. The aim of the present study was to characterize the effects of acute
      LHS on two populations of spinal neurons (F and E) mediating PLRs. For this
      purpose, in decerebrate rabbits, responses of individual neurons from L5 to
      stimulation causing PLRs were recorded before and during reversible LHS (caused
      by temporal cold block of signal transmission in lateral spinal pathways at L1),
      as well as after acute surgical LHS at L1. Results obtained after Sur-LHS were
      compared to control data obtained in our previous study. We found that acute LHS
      caused disappearance of PLRs on the affected side. It also changed a proportion
      of different types of neurons on that side. A significant decrease and increase
      in the proportion of F- and non-modulated neurons, respectively, was found. LHS
      caused a significant decrease in most parameters of activity in F-neurons located
      in the ventral horn on the lesioned side and in E-neurons of the dorsal horn on
      both sides. These changes were caused by a significant decrease in the efficacy
      of posture-related sensory input from the ipsilateral limb to F-neurons, and from
      the contralateral limb to both F- and E-neurons. These distortions in operation
      of postural networks underlie the impairment of postural control after acute LHS,
      and represent a starting point for the subsequent recovery of postural functions.

PMID- 27702649
TI  - A complete mitochondrial genome from Echinochasmus japonicus supports the
      elevation of Echinochasminae Odhner, 1910 to family rank (Trematoda:
      Platyhelminthes).
AB  - The complete mitochondrial (mt) genome of the trematode Echinochasmus japonicus
      Tanabe, 1926 was fully determined and annotated. The circular mt molecule of this
      species is 15,865bp in length, containing 12 protein-coding genes (arranged in
      the following order: cox3-cob-nad4L-nad4-atp6-nad2-nad1-nad3-cox1-cox2-nad6
      nad5), two ribosomal RNA genes (rrnL and rrnS) and 22 transfer RNA genes (trnH;
      trnQ; trnF; trnM; trnV; trnA; trnD; trnN; trnP; trnI; trnK; trnS1(AGN); trnW;
      trnT; trnC; trnL1(CUN); trnS2(UCN); trnL2(UUN); trnG; and trnE). The atp8 gene is
      absent. The 3' end of nad4L overlaps the 5' end of nad4 by 40bp. An array of
      eight identical tandem repeats (240bp each) was found between trnG and trnE in
      the long non-coding region of the individual worm sequenced. Numbers of these
      repeats varied among E. japonicus samples. Phylogenetic analysis of concatenated
      mt protein sequences of 40 trematode species/strains supports the elevation of
      Echinochasminae Odhner, 1910 to family rank, close to the families
      Echinostomatidae and Fasciolidae. As echinochasmid and echinostomatid species can
      parasitize humans, the future characterization of additional mt genomes is needed
      for development of mt markers for identification and phylogenetic, population,
      epidemiological and hybridization studies.

PMID- 27702650
TI  - Central leptin action on euglycemia restoration in type 1 diabetes: Restraining
      responses normally induced by fasting?
AB  - Leptin monotherapy is sufficient to restore euglycemia in insulinopenic type 1
      diabetes (T1D), yet the underlying mechanism remains poorly understood.
      Accumulating evidence demonstrates that the brain mediates the leptin action on
      euglycemia restoration. Here, we first review evidence supporting that symptoms
      in T1D resemble an uncontrolled response to fasting. Then, we discuss recent
      research progress on brain neurons and their neurotransmitters that potentially
      mediate the leptin action. Finally, peripheral effective pathways, which are
      normally involved in fasting responses and associated with leptin action on
      euglycemia restoration in T1D, will also be discussed. This summary complements
      several previous excellent reviews on this topic (Meek and Morton, 2016; Perry et
      al., 2016; Fujikawa and Coppari, 2015). A deep understanding of neurocircuitry
      and the peripheral effective pathways that mediate the leptin action on
      euglycemia restoration will likely lead to novel targets for an insulin
      independent therapeutics against T1D.

PMID- 27702652
TI  - Prolyl hydroxylase domain enzymes and their role in cell signaling and cancer
      metabolism.
AB  - The prolyl hydroxylase domain (PHD) enzymes regulate the stability of the hypoxia
      inducible factor (HIF) in response to oxygen availability. During oxygen
      limitation, the inhibition of PHD permits the stabilization of HIF, allowing the
      cellular adaptation to hypoxia. This adaptation is especially important for solid
      tumors, which are often exposed to a hypoxic environment. However, and despite
      their original role as the oxygen sensors of the cell, PHD are currently known to
      display HIF-independent and hydroxylase-independent functions in the control of
      different cellular pathways, including mTOR pathway, NF-kB pathway, apoptosis and
      cellular metabolism. In this review, we summarize the recent advances in the
      regulation and functions of PHD in cancer signaling and cell metabolism.

PMID- 27702653
TI  - UCN enhances TGF-beta-mediated mitoinhibition of VSMCs via counteracting TGF-beta
      induced cPLA2 expression and activation.
AB  - Urocortins (UCNs) and transforming growth factor-beta (TGF-beta) have been
      demonstrated to participate in various cardiovascular diseases, many of which
      involve vascular smooth muscle cells (VSMCs) proliferation. Cytosolic
      phospholipase A2 (cPLA2)-mediated arachidonic acid (AA) release is an important
      cause of VSMCs proliferation. The work was to investigate the regulation of VSMCs
      proliferation by UCN/TGF-beta and whether cPLA2 was a link between their
      signaling pathways. VSMCs proliferation was measured by colorimetric assay and
      immunofluorescence microscopy. Using cell flow cytometry, the changes in the cell
      cycle phases were investigated. Lentiviral Vector Particle was performed to
      overexpress cPLA2 gene. Both UCN and TGF-beta inhibited VSMCs proliferation and
      an additive effect was observed when the cells were treated with UCN plus TGF
      beta. TGF-beta increased the percentage of cells in G1-phase while UCN increased
      the cell percentage in G2-phase with a concomitant decrease in S-phase.
      Furthermore, cPLA2 expression was increased by TGF-beta but decreased by UCN and
      UCN attenuated TGF-beta-induced cPLA2 expression. In primary VSMCs, TGF-beta
      induced cPLA2 phosphorylation, and this effect was also attenuated by UCN.
      Similar to UCN, the cPLA2 inhibitor, pyrrophenone (PYR), also played a role in
      enhancing TGF-beta-mediated mitoinhibition. Inversely, overexpression of cPLA2
      eliminated the effect of UCN on the mitoinhibition. The pretreatment with UCN
      counteracted TGF-beta-mediated cPLA2 expression and activation, thereby
      contributing to TGF-beta-mediated mitoinhibition of VSMCs.

PMID- 27702651
TI  - Phosphorylation of MITF by AKT affects its downstream targets and causes TP53
      dependent cell senescence.
AB  - Microphthalmia-associated transcription factor (MITF) plays a crucial role in the
      melanogenesis and proliferation of melanocytes that is dependent on its abundance
      and modification. Here, we report that epidermal growth factor (EGF) induces
      senescence and cyclin-dependent kinase inhibitor 1A (CDKN1A) expression that is
      related to MITF. We found that MITF could bind TP53 to regulate CDKN1A.
      Furthermore, the interaction between MITF and TP53 is dependent on AKT activity.
      We found that AKT phosphorylates MITF at S510. Phosphorylated MITF S510 enhances
      its affinity to TP53 and promotes CDKN1A expression. Meanwhile, the
      unphosphorylative MITF promotes TYR expression. The levels of p-MITF-S510 are low
      in 90% human melanoma samples. Thus the level of p-MITF-S510 could be a possible
      diagnostic marker for melanoma. Our findings reveal a mechanism for regulating
      MITF functions in response to EGF stimulation and suggest a possible
      implementation for preventing the over proliferation of melanoma cells.

PMID- 27702654
TI  - Bone morphogenetic protein 2 promotes osteogenesis of bone marrow stromal cells
      in type 2 diabetic rats via the Wnt signaling pathway.
AB  - Type 2 diabetes mellitus impairs osteogenesis in bone marrow stromal cells
      (BMSCs). Bone morphogenetic protein 2 (BMP2) has been extensively applied for
      bone defect restoration and has been shown to activate the Wnt signaling pathway.
      The objective of this study was to investigate the effects of BMP2 on the cell
      proliferation and osteogenesis of type 2 diabetic BMSCs in rats and explore
      whether BMP2 induced osteogenesis via the stimulation of Wnt signaling pathway.
      The cell experiments were divided into DM (diabetic BMSCs), BMP25 (induced with
      25ng/ml BMP2), BMP100 (induced with 100ng/ml BMP2) and BMP25 +XAV groups. All
      cells with or without the different concentrations of BMP2 were cultured under
      the same experimental conditions. The in vitro results indicated that BMP2
      enhanced cell proliferation by 130%-157% and osteogenic differentiation by
      approximately two-fold in type 2 diabetic BMSCs. The expression levels of beta
      catenin, cyclin D1, Runx2 and c-myc related to the Wnt signaling pathway were
      also upregulated from 180% to 212% in BMP2-induced type 2 diabetic rat BMSCs,
      while the level of GSK3beta decreased to 43%. In BMP2-induced type 2 diabetic
      BMSCs with calcium phosphate cement (CPC) scaffolds for osteoblast study in vivo,
      the appearance of newly formed bone dramatically increased to 175% compared with
      type 2 diabetic BMSCs. These data demonstrated that BMP2 enhanced bone
      regeneration in diabetic BMSCs by stimulating the Wnt signaling pathway with the
      accumulation of beta-catenin and the depressed expression of GSK3beta. Diabetic
      BMSCs associated with BMP2 might be a potential tissue-engineered construct for
      bone defects in type 2 diabetes mellitus.

PMID- 27702656
TI  - A framework to establish credibility of computational models in biology.
AB  - Computational models in biology and biomedical science are often constructed to
      aid people's understanding of phenomena or to inform decisions with socioeconomic
      consequences. Model credibility is the willingness of people to trust a model's
      predictions and is often difficult to establish for computational biology models.
      A 3 * 3 matrix has been proposed to allow such models to be categorised with
      respect to their testability and epistemic foundation in order to guide the
      selection of an appropriate process of validation to supply evidence to establish
      credibility. Three approaches to validation are identified that can be deployed
      depending on whether a model is deemed untestable, testable or lies somewhere in
      between. In the latter two cases, the validation process involves the
      quantification of uncertainty which is a key output. The issues arising due to
      the complexity and inherent variability of biological systems are discussed and
      the creation of 'digital twins' proposed as a means to alleviate the issues and
      provide a more robust, transparent and traceable route to model credibility and
      acceptance.

PMID- 27702657
TI  - PH-sensitive bionanocomposite hydrogel beads based on carboxymethyl cellulose/ZnO
      nanoparticle as drug carrier.
AB  - The present work explains the preparation of new pH-sensitive bionanocomposite
      beads based on carboxymethyl cellulose (CMC) and ZnO nanoparticles for use as
      controlled release drug delivery systems. Fe3+ ion as physical crosslinking agent
      was used to prepare ionic cross-linked bionanocomposite hydrogel beads.
      Propranolol hydrochloride (PPN) has been chosen as a model drug. Characterization
      of the pH-sensitive bionanocomposite beads resulting from incorporation of
      different content of ZnO nanoparticles into CMC matric was carried out using
      different experimental techniques: XRD, FT-IR, TGA, SEM and EDX. Propranolol
      incorporation efficiency in beads was determined by UV-vis spectroscopy and was
      found to be high. Moreover, the swelling and drug release properties of the
      bionanocomposite hydrogels were investigated. The prepared bionanocomposite beads
      showed a pH sensitive swelling behavior with maximum water absorbing at pH 7.4.
      Also, it was found that the swelling ratio of ZnO/CMC hydrogels in different
      aqueous solutions was rather higher in comparison with its neat hydrogel. In
      vitro drug release test was carried out to prove the effectiveness of this novel
      type of bionanocomposite hydrogel beads as a controlled drug delivery system. A
      more sustained and controlled drug releases were observed for ZnONPs containing
      NaCMC beads, which increased by the increase in ZnONPs content.

PMID- 27702658
TI  - Inhibition of lysozyme fibrillation by human serum albumin nanoparticles:
      Possible mechanism.
AB  - Amyloid fibrillation is a prevalent phenomenon in different proteins and
      peptides, which results in a variety of disorders. Over the last decade,
      implementation of nanoparticles (NPs), with or without drugs, is considered as a
      promising approach to protect against the aggregation process of amyloid
      proteins. In this study, we investigated the effect of human serum albumin NPs
      (HSA NPs) on the fibrillation of Hen Egg White Lysozyme (HEWL). The results
      showed that HSA NPs decrease the fibrillation of HEWL in a size dependent manner.
      Surprisingly, despite their inhibitory effects on the formation of long fibrils,
      our studies revealed that the NPs do not preserve the stability of the protein's
      structure in denaturing conditions. In fact, different structural analysis
      methods revealed that in the presence of the NPs, the protein's tendency to
      expose hydrophobic patches increased. Therefore, it seems that HSA NPs are
      responsible for decrease in HEWL fibrillation by reducing its concentration and
      blocking hot spot regions for self-assembly via moderate interaction.
      Collectively, our results shed light on the impact of HSA NPs on HEWL
      fibrillation and open new challenges on the implications of these NPs for drug
      delivery purposes or direct use as therapeutic agents.

PMID- 27702659
TI  - Study of the UV protective and antibacterial properties of aqueous polyurethane
      dispersions extended with low molecular weight chitosan.
AB  - A series of aqueous dispersions of polyurethane (PU) and low molecular weight
      chitosan (CS(LMW)) has been prepared in two steps synthetic process. In first
      step PU prepolymer, with NCO termini were prepared by reacting isophrone
      diisocyanate (IPDI), poly (caprolactone) diol (CAPA, Mn 1000), and 2,2-dimethylol
      propionic acid (DMPA), followed by neutralization of PU prepolymer with
      triethylamine (TEA). In second step PU prepolymer chain was extended by low
      molecular weight chitosan followed by dispersion formation by adding calculated
      volume of water. Molecular characterization of CS(LMW)-PU finishes was done by
      FTIR and application on poly-cotton blended fabric samples was confirmed by
      scanning electron microscopy (SEM). Antimicrobial and UV protective performance
      of treated fabrics was performed by AATCC 100 and AATCC TM183 methods
      respectively. Furthermore, it shows that the addition of chitosan remarkably
      increases antimicrobial and UV protective properties of PUs.

PMID- 27702660
TI  - Vasohibin 2 promotes human luminal breast cancer angiogenesis in a non-paracrine
      manner via transcriptional activation of fibroblast growth factor 2.
AB  - Vasohibin 2 (VASH2) is an angiogenic factor and cancer-related protein that acts
      via paracrine mechanisms. Here, we investigated the angiogenic function and
      mechanism of action of VASH2 in 200 human breast cancer tissues by performing
      immunohistochemical staining, western blot, indirect sandwich enzyme-linked
      immunosorbent assay (ELISA), and a semi-quantitative sandwich-based antibody
      array. Breast cancer cells stably overexpressing VASH2 or with knocked-down VASH2
      were established and used for in vivo and in vitro models. In human luminal
      tissue, but not in HER2-positive or basal-like breast cancer tissues, VASH2 was
      positively correlated with CD31-positive microvascular density, induced
      angiogenesis in xenograft tumors, and promoted human umbilical vein endothelial
      cell tube formation in vitro. VASH2 expression was absent in the concentrated
      conditioned medium collected from knocked-down VASH2 and VASH2-overexpressing
      luminal breast cancer cells. Further, VASH2 regulated the expression of
      fibroblast growth factor 2 (FGF2) in human luminal breast cancer cells, and the
      pro-angiogenic effect induced by VASH2 overexpression was blocked by FGF2
      neutralization in vitro. Additionally, dual luciferase reporter assay and
      Chromatin immunoprecipitation analysis results showed that FGF2 promoter was
      transcriptionally activated by VASH2 via histone modifications. In conclusion,
      VASH2 expression is positively correlated with FGF2 expression and promotes
      angiogenesis in human luminal breast cancer by transcriptional activation of
      fibroblast growth factor 2 through non-paracrine mechanisms.

PMID- 27702661
TI  - Osteopontin induces autophagy to promote chemo-resistance in human hepatocellular
      carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is a major health burden worldwide for its high
      incidence and mortality. Osteopontin (OPN) is a chemokine-like, matricellular
      phosphoglycoprotein whose expression is elevated in various types of cancer
      including HCC. OPN has been shown to be involved in tumorigenesis, chemo
      resistance, metastasis and sustaining stem-like properties of cancer cells.
      Autophagy is a cellular process by which cytoplasmic components are degraded and
      recycled for maintaining cellular homeostasis. There is increasing evidence
      supports that autophagy plays a critical role for stem-like properties and chemo
      resistance of cancer cells. However, the relationship between OPN and autophagy
      in maintaining cancer stem-like properties and chemo-resistance is yet to be
      clarified. Herein, we found that secreted OPN induced autophagy via binding with
      its receptor integrin alphavbeta3 and sustaining FoxO3a stability. OPN-elicited
      autophagy could promote cancer cell survival and resistance to chemotherapy
      drugs, as well as stem-like properties. Our findings indicated that OPN was
      capable of promoting chemo-resistance of HCCs via autophagy, which might provide
      a new strategy for the treatment of HCC.

PMID- 27702655
TI  - Transmural gradients in ion channel and auxiliary subunit expression.
AB  - Evolution has acted to shape the action potential in different regions of the
      heart in order to produce a maximally stable and efficient pump. This has been
      achieved by creating regional differences in ion channel expression levels within
      the heart as well as differences between equivalent cardiac tissues in different
      species. These region- and species-dependent differences in channel expression
      are established by regulatory evolution, evolution of the regulatory mechanisms
      that control channel expression levels. Ion channel auxiliary subunits are
      obvious targets for regulatory evolution, in order to change channel expression
      levels and/or modify channel function. This review focuses on the transmural
      gradients of ion channel expression in the heart and the role that regulation of
      auxiliary subunit expression plays in generating and shaping these gradients.

PMID- 27702662
TI  - Upregulation of SNHG6 regulates ZEB1 expression by competitively binding miR-101
      3p and interacting with UPF1 in hepatocellular carcinoma.
AB  - Emerging evidence suggests that small nucleolar RNAs (snoRNAs) and their host
      genes (SNHGs) have malfunctioning roles in the development of human cancers. We
      globally investigated the molecular mechanisms by which snoRNA host gene 6
      (SNHG6) promotes hepatocellular carcinoma (HCC) progression using human tissues
      and cell lines. We found that SNHG6 is overexpressed in HCC tissues and in
      hepatoma cell lines and is closely associated with histologic grade, hepatitis B
      virus DNA, Barcelona Clinic Liver Cancer stage and portal vein tumor thrombus in
      patients with HCC. Knockdown of SNHG6 induced apoptosis and repressed cell cycle
      progression in hepatoma cell lines, whereas transgenic expression of SNHG6 in the
      immortalized human hepatic cell line L02 had opposite effects. Xenograft tumors
      grown from SNHG6-knockdown cells had smaller mean volumes than did tumors grown
      from control cells. SNHG6 may act as a competing endogenous RNA, effectively
      becoming a sink for miR-101-3p and thereby modulating the derepression of zinc
      finger E-box binding homeobox 1, imposing an additional level of post
      transcriptional regulation. Functionally, SNHG6 promotes tumor growth and
      metastasis by inducing epithelial to mesenchymal transition. Further
      investigations showed that SNHG6 could affect HCC tumorigenesis by binding to up
      frameshift protein 1 and regulating Smad7 expression.

PMID- 27702663
TI  - Evaluation of the cytotoxic and genotoxic effects of benchmark multi-walled
      carbon nanotubes in relation to their physicochemical properties.
AB  - To contribute with scientific evidence to the grouping strategy for the safety
      assessment of multi-walled carbon nanotubes (MWCNTs), this work describes the
      investigation of the cytotoxic and genotoxic effects of four benchmark MWCNTs in
      relation to their physicochemical characteristics, using two types of human
      respiratory cells. The cytotoxic effects were analysed using the clonogenic assay
      and replication index determination. A 48h-exposure of cells revealed that NM-401
      was the only cytotoxic MWCNT in both cell lines, but after 8-days exposure, the
      clonogenic assay in A549 cells showed cytotoxic effects for all the tested
      MWCNTs. Correlation analysis suggested an association between the MWCNTs size in
      cell culture medium and cytotoxicity. No induction of DNA damage was observed
      after any MWCNTs in any cell line by the comet assay, while the micronucleus
      assay revealed that both NM-401 and NM-402 were genotoxic in A549 cells. NM-401
      and NM-402 are the two longest MWCNTs analyzed in this work, suggesting that
      length may be determinant for genotoxicity. No induction of micronuclei was
      observed in BBEAS-2Beas-2B cell line and the different effect in both cell lines
      is explained in view of the size-distribution of MWCNTs in the cell culture
      medium, rather than cell's specificities.

PMID- 27702664
TI  - Impact of R264C and R264H polymorphisms in human aromatase function.
AB  - The cytochrome P450 aromatase is involved in the last step of sex hormones
      biosynthesis by converting androgens into estrogens. The human enzyme is highly
      polymorphic and literature data correlate aromatase single nucleotide
      polymorphisms to the onset of pathologies such as breast cancer and
      neurodegenerative diseases. The aims of this study were i) to study the influence
      of the mutations R264C and R264H on the structure-function of the enzyme also
      upon phosphorylation by selected kinases and ii) to compare the activity of the
      variants to that of aromatase wild type in two different cell lines. Far-UV
      circular dichroism spectroscopy, thermal denaturation experiments and CO-binding
      assay showed that the two polymorphic variants are correctly folded. Steady-state
      kinetics experiments showed that rArom R264C and R264H exhibit a 1.5 and 3.4
      folds lower catalytic efficiency, respectively, when compared to the wild type
      protein. Since R264 is part of the consensus motif of PKA and PKG1,
      phosphorylation experiments were performed to study the effect on aromatase
      function. Phosphorylation by PKA caused a decrease in activity by 36.2%, 49.3%
      and 27.9% in the wild type, R264C and R264H proteins respectively.
      Phosphorylation by PKG1 was also found to decrease the activity by 30.3%, 30.5%
      and 15.4% in the wild type, R264C and R264H proteins respectively. Experiments
      performed on the three full-length proteins expressed in human MCF-7 breast
      cancer cells and rat ST14A neuronal cells showed that, depending on the cell line
      used, the activity of the proteins is different, implicating different cellular
      mechanisms modulating aromatase activity. This work demonstrate that R264
      polymorphism causes an intrinsic alteration of aromatase activity together with a
      different consensus for phosphorylation by different kinases, indicating that
      estrogen production can be different when such mutations are present. These
      findings are significant in understanding the onset and treatment of pathologies
      in which aromatase has been shown to be involved.

PMID- 27702665
TI  - A new acetophenone glycoside from the flower buds of Syzygium aromaticum
      (cloves).
AB  - A new acetophenone, 2,4,6-trihydroxy-3-methylacetophenone-2-O-beta-d-glucoside
      (1), together with 21 known compounds; one acetophenone (2), four chromone
      glycosides (3-6), six phenylpropanoids (7-12), six sesquiterpenoids (13-18), two
      triterpenoids (19 and 20), one sterol (21), and one tannin (22) were isolated
      from the flower buds of Syzygium aromaticum (cloves). The structure of the new
      compound 1 was determined by spectroscopic analyses including 1D-, 2D-NMR and
      HRMS interpretation. Among the isolates, one acetophenone (2), three
      phenylpropanoids (10-12), and one sesquiterpenoid (13) were isolated from the
      flower buds of S. aromaticum for the first time in this study. All the isolates
      (1-22) were evaluated for their cytotoxicity against human ovarian cancer cells
      (A2780) using MTT assays. Some of the isolates (5, 6, 9, 15, 17, 19, 20, and 21)
      showed either moderate or weak cytotoxicity on A2780 cells.

PMID- 27702666
TI  - Identification and characterization of naturally occurring inhibitors against
      human carboxylesterase 2 in White Mulberry Root-bark.
AB  - White Mulberry Root-bark (WMR) is an edible Chinese herbal used for the treatment
      of inflammation, nephritis and asthma. This study aimed to investigate the
      inhibitory effects of ethanol extract from WMR against human carboxylesterase 2
      (hCE2), as well as to identity and character natural hCE2 inhibitors in this
      herbal. Our results demonstrated that the ethanol extract of WMR displayed potent
      inhibitory effects against hCE2, while three major bioactive constitutes in WMR
      were identified on the basis of LC fingerprinting combined with activity-based
      screening of LC fractions. Three bioactive compounds including SD, KG and SC were
      efficiently identified by comparison of LC retention times, UV and MS spectral
      data, with the help of authentic standards. The inhibition potentials and
      inhibition types of these natural compounds against hCE2 were further
      investigated in human liver microsomes. The results demonstrated that these
      bioactive compounds are potent non-competitive inhibitors against hCE2, with the
      Ki values ranging from 0.76MUM to 1.09MUM. All these findings suggested that
      three abundant natural compounds in WMR displayed potent inhibitory effects
      against hCE2, which could be used as lead compounds to develop more potent hCE2
      inhibitors for the alleviation of hCE2-mediated severe delayed-onset diarrhea.

PMID- 27702667
TI  - Antibacterial screening of Juncaceae species native to the Carpathian Basin
      against resistant strains and LC-MS investigation of phenanthrenes responsible
      for the effect.
AB  - The main objective of this project was to investigate the antibacterial activity
      of 19 species (Juncus acutus, J. alpinoarticulatus, J. articulatus, J.
      compressus, J. conglomeratus, J. effusus, J. filiformis, J. gerardii, J.
      inflexus, J. maritimus, J. monanthos, J. squarrosus, J. tenuis, J. trifidus,
      Luzula campestris, L. forsteri, L. luzuloides, L. sudetica and L. sylvatica)
      belonging to the family Juncaceae against methicillin-resistant S. aureus (MRSA),
      extended-spectrum beta-lactamase (ESBL)-producing C. freundii, E. coli, E.
      cloacae, K. pneumoniae, and multiresistant A. baumannii and P. aeruginosa.
      Antibacterial susceptibilities were screened for inhibitory zones and MIC values
      determined by microdilution method. Among the tested extracts (n=96) 16 extracts
      prepared from Juncus species and 3 extracts from Luzula species showed mild to
      strong inhibitory activities against MRSA strains (inhibition zones=6.7mm-14.6mm;
      MIC values 9.75-156MUg/mL). It can be concluded that Juncus and Luzula species
      demonstrated promising anti-MRSA effect, and J. maritimus, J. tenuis and J.
      gerardii considered worthy of activity-guided phytochemical investigations. The
      main bioactive constituents of Juncaceae species are phenanthrenes. Four
      phenanthrenes [juncuenin D (1), juncusol (2), dehydrojuncuenin B (3), and
      jinflexin B (4)] isolated previously from J. inflexus with anti-MRSA activity
      were investigated by LC-MS in extracts proved to be active in antimicrobial test.

PMID- 27702669
TI  - The General's Goiter: The Outcome of a Subtotal Thyroidectomy Performed on United
      States Army General George Catlett Marshall.

PMID- 27702668
TI  - Influence of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of
      various novel antiepileptic drugs against maximal electroshock-induced seizures
      in mice.
AB  - The aim of this study was to determine the effects of xanthotoxin (8
      methoxypsoralen) on the protective action of 5 various second- and third
      generation antiepileptic drugs (i.e., lacosamide, lamotrigine, oxcarbazepine,
      pregabalin and topiramate) in the mouse maximal electroshock-induced seizure
      model. Seizure activity was evoked in adult male albino Swiss mice by a current
      (25mA, 500V, 0.2s stimulus duration) delivered via auricular electrodes. Drug
      related adverse effects were determined in the chimney, grip-strength and passive
      avoidance tests. Total brain antiepileptic drug concentrations were measured to
      confirm pharmacodynamic nature of observed interactions with xanthotoxin. Results
      indicate that xanthotoxin (100mg/kg, i.p.) significantly enhanced the
      anticonvulsant action of lacosamide (P<0.01), oxcarbazepine (P<0.05), pregabalin
      (P<0.01), and topiramate (P<0.001), but not that of lamotrigine in the maximal
      electroshock-induced seizure test. Moreover, xanthotoxin (50mg/kg) still
      significantly potentiated the anticonvulsant action of lacosamide (P<0.05),
      pregabalin (P<0.05), and topiramate (P<0.001) in this seizure test. Xanthotoxin
      had no significant impact on total brain concentrations of the studied
      antiepileptic drugs in mice. Furthermore, combinations of xanthotoxin with
      oxcarbazepine or topiramate produced no adverse effects. However, xanthotoxin in
      combination with lacosamide, lamotrigine or pregabalin significantly reduced
      muscular strength in mice in the grip-strength test. In the chimney test, only
      the combinations of xanthotoxin with pregabalin significantly impaired motor
      coordination in mice. In conclusion, the combinations of xanthotoxin with
      oxcarbazepine and topiramate produce beneficial anticonvulsant pharmacodynamic
      interactions in the maximal electroshock-induced seizure test. A special caution
      is advised when combining xanthotoxin with pregabalin due to appearance of acute
      adverse effects.

PMID- 27702670
TI  - Mammalian target of rapamycin inhibition counterbalances the inflammatory status
      of immune cells in patients with chronic granulomatous disease.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency
      caused by defective production of reactive oxygen species in phagocytic cells
      that results in life-threatening infections and severe inflammatory
      manifestations. The treatment of inflammatory manifestations remains challenging
      because it can be associated with an increased risk of infections. Previous
      studies have shown that phagocytes from patients with CGD display a defect in
      autophagy and a reactive oxygen species-independent activation of the
      inflammasome. OBJECTIVE: Because the intersections between autophagy and the
      inflammasome have been observed in patients with various diseases and microbial
      infections, we investigated the possible benefit of restoring the autophagy
      defect through rapamycin, a potent autophagy inducer, in the setting of CGD.
      METHODS: We studied 15 patients given a diagnosis of CGD and followed in our
      institution. All patients were free of any active infection at the time of the
      study. RESULTS: We show that patients with CGD present a consistent inflammatory
      phenotype defined by (1) increased nonclassical and intermediate monocytes, (2) a
      proinflammatory state of mononuclear phagocytes with increased IL-1beta and TNF
      alpha content, (3) a TH17 bias of CD4+ T cells, (4) and an increase in IL-17A
      secreting neutrophil numbers. We document the reversion of CGD inflammatory
      status by the mammalian target of rapamycin inhibitor rapamycin on the different
      immune cell subsets. We also provide evidence for the enhancement of rapamycin's
      inhibitory effect on IL-1beta secretion by the IL-1 receptor antagonist anakinra
      in phagocytes of patients with CGD. CONCLUSION: Altogether, these data open new
      therapeutic approaches for CGD-related inflammatory manifestations.

PMID- 27702671
TI  - Major differences between human atopic dermatitis and murine models, as
      determined by using global transcriptomic profiling.
AB  - BACKGROUND: Atopic dermatitis (AD) is caused by a complex interplay between
      immune and barrier abnormalities. Murine models of AD are essential for
      preclinical assessments of new treatments. Although many models have been used to
      simulate AD, their transcriptomic profiles are not fully understood, and a
      comparison of these models with the human AD transcriptomic fingerprint is
      lacking. OBJECTIVE: We sought to evaluate the transcriptomic profiles of 6 common
      murine models and determine how they relate to human AD skin. METHODS:
      Transcriptomic profiling was performed by using microarrays and quantitative RT
      PCR on biopsy specimens from NC/Nga, flaky tail, Flg-mutated, ovalbumin
      challenged, oxazolone-challenged, and IL-23-injected mice. Gene expression data
      of patients with AD, psoriasis, and contact dermatitis were obtained from
      previous patient cohorts. Criteria of a fold change of 2 or greater and a false
      discovery rate of 0.05 or less were used for gene arrays. RESULTS: IL-23
      injected, NC/Nga, and oxazolone-challenged mice show the largest homology with
      our human meta-analysis-derived AD transcriptome (37%, 18%, 17%, respectively).
      Similar to human AD, robust TH1, TH2, and also TH17 activation are seen in IL-23
      injected and NC/Nga mice, with similar but weaker inflammation in ovalbumin
      challenged mice. Oxazolone-challenged mice show a TH1-centered reaction, and
      flaky tail mice demonstrate a strong TH17 polarization. Flg-mutated mice display
      filaggrin downregulation without significant inflammation. CONCLUSION: No single
      murine model fully captures all aspects of the AD profile; instead, each model
      reflects different immune or barrier disease aspects. Overall, among the 6 murine
      models, IL-23-injected mice best simulate human AD; still, the translational
      focus of the investigation should determine which model is most applicable.

PMID- 27702672
TI  - Human milk oligosaccharides and development of cow's milk allergy in infants.

PMID- 27702674
TI  - Cytotoxic effects of Aeromonas hydrophila culture supernatant on peripheral blood
      leukocytes of Nile tilapia (Oreochromis niloticus): Possible presence of a
      secreted cytotoxic lectin.
AB  - Number of exotoxins like haemolysin, leukocidin, aerolysin etc. were reported
      from Aeromonas hydrophila. In this study, we report the haemolytic and cytotoxic
      effect of A. hydrophila culture supernatant (CS) that is specifically inhibited
      by lactose and also by serum and mucus of Nile tilapia (Oreochromis niloticus).
      Hence, we assume the presence of a secreted lectin in the CS. CS is toxic to
      peripheral blood leukocytes (PBL) of O. niloticus as revealed by MTT assay and by
      flow cytometry. DNA laddering assay indicates that CS causes necrosis to PBL. As
      a result of necrosis, CS treated PBL showed increased production of reactive
      oxygen species as indicated by nitroblue tetrazolium and 2',7' 
      dichlorofluorescin diacetate assays. CS treated PBL showed reduced mRNA
      expression of TNF-alpha and IFN-gamma genes. When CS was subjected to
      polyacrylamide gel electrophoresis, it showed a single band corresponding to the
      molecular weight of 45 kDa. However, upon concentrating the CS by
      ultrafiltration, many bands were visualized. Further studies at molecular level
      are required to unravel this macromolecular-leukocyte interaction which would
      ultimately benefit the aquaculture industry.

PMID- 27702673
TI  - Mechanism of TH2/TH17-predominant and neutrophilic TH2/TH17-low subtypes of
      asthma.
AB  - BACKGROUND: The mechanism of TH2/TH17-predominant and TH2/TH17-low asthma is
      unknown. OBJECTIVE: We sought to study the immune mechanism of TH2/TH17
      predominant and TH2/TH17-low asthma. METHODS: In a previously reported cohort of
      60 asthmatic patients, 16 patients were immunophenotyped with TH2/TH17
      predominant asthma and 22 patients with TH2/TH17-low asthma. We examined
      bronchoalveolar lavage (BAL) fluid leukocytes, cytokines, mediators, and
      epithelial cell function for these asthma subgroups. RESULTS: Patients with
      TH2/TH17-predominant asthma had increased IL-1beta, IL-6, IL-23, C3a, and serum
      amyloid A levels in BAL fluid, and these correlated with IL-1beta and C3a levels.
      TH2/TH17 cells expressed higher levels of the IL-1 receptor and phospho-p38
      mitogen-activated protein kinase. Anakinra, an IL-1 receptor antagonist protein,
      inhibited BAL TH2/TH17 cell counts. TH2/TH17-low asthma had 2 distinct subgroups:
      neutrophilic asthma (45%) and pauci-inflammatory asthma (55%). This contrasted
      with patients with TH2/TH17-predominant and TH2-predominant asthma, which
      included neutrophilic asthma in 6% and 0% of patients, respectively. BAL fluid
      neutrophils strongly correlated with BAL fluid myeloperoxidase, IL-8, IL-1alpha,
      IL-6, granulocyte colony-stimulating factor, and GM-CSF levels. Sixty percent of
      the patients with neutrophilic asthma had a pathogenic microorganism in BAL
      culture, which suggested a subclinical infection. CONCLUSION: We uncovered a
      critical role for the IL-1beta pathway in patients with TH2/TH17-predminant
      asthma. A subgroup of patients with TH2/TH17-low asthma had neutrophilic asthma
      and increased BAL fluid IL-1alpha, IL-6, IL-8, granulocyte colony-stimulating
      factor, and GM-CSF levels. IL-1alpha was directly involved in IL-8 production and
      likely contributed to neutrophilic asthma. Sixty percent of neutrophilic patients
      had a subclinical infection.

PMID- 27702675
TI  - Proteomic and metabolomic responses in D-shape larval mussels Mytilus
      galloprovincialis exposed to cadmium and arsenic.
AB  - Cadmium (Cd) and arsenic (As) are the main metal/metalloid contaminants in the
      coastal environments of the Bohai Sea, China. In this work, a combined proteomic
      and metabolomic approach was applied to investigate the biological effects of Cd
      and As (V) in the early life stage (D-shape larvae) of mussel Mytilus
      galloprovincialis. Results indicated that Cd was a potential immune toxicant to D
      shape larval mussel because of the numerous proteomic responses related to immune
      system. Additionally, Cd induced oxidative stress, cellular injury and
      disturbance in nucleic acid metabolism in D-shape larval mussels. However, only
      two identified proteins were significantly altered in As (V)-treated group,
      suggesting that D-shape larval mussel was less sensitive to As (V) than to Cd at
      protein level. These two proteins in response to As (V) suggested that As (V)
      influenced anti-oxidative system and cell proliferation in D-shape larval
      mussels. Metabolic responses indicated that Cd and As (V) induced disturbances in
      osmotic regulation and energy metabolism in D-shape larval mussels via different
      metabolic pathways. In addition, Cd reduced lipid metabolism as well. This work
      demonstrated that a combination of proteomics and metabolomics could provide an
      insightful view in the biological effects of pollutants in mussel M.
      galloprovincialis at an early life stage.

PMID- 27702676
TI  - Oreochromis mossambicus diet supplementation with Psidium guajava leaf extracts
      enhance growth, immune, antioxidant response and resistance to Aeromonas
      hydrophila.
AB  - In this research, we focused on the efficacy of aqueous and ethanol leaf extracts
      of Psidium guajava L. (guava) based experimental diets on the growth, immune,
      antioxidant and disease resistance of tilapia, Oreochromis mossambicus following
      challenge with Aeromonas hydrophila. The experimental diets were prepared by
      mixing powdered (1, 5 and 10 mg/g) aqueous and ethanol extract of guava leaf with
      commercial diet. The growth (FW, FCR and SGR), non-specific cellular immune
      (myeloperoxidase activity, reactive oxygen activity and reactive nitrogen
      activity) humoral immune (complement activity, antiprotease, alkaline phosphatase
      activity and lysozyme activity) and antioxidant enzyme responses (SOD, GPX, and
      CAT) were examined after 30 days of post-feeding. A significant enhancement in
      the biochemical and immunological parameters of fish were observed fed with
      experimental diets compared to control. The dietary supplementation of P. guajava
      leaf extract powder for 30 days significantly reduced the mortality and increased
      the disease resistance of O. mossambicus following challenge with A. hydrophila
      at 50 MUl (1 * 107 cells ml-1) compared to control after post-infection. The
      results suggest that the guava leaf extract could be used as a promising feed
      additive in aquaculture.

PMID- 27702678
TI  - Parental care improves immunity in the seahorse (Hippocampus erectus).
AB  - In the present study, the sexual dimorphism in immune response in the seahorse
      Hippocampus erectus in which males compete for mates and invest heavily in
      parental care was assessed. Variability in immunocompetence in virginal seahorses
      with differing levels of sexual maturity (i.e., immaturity, early maturity and
      maturity) and with different mating statuses (i.e., virginal, experienced mating
      failure and experienced mating success) were analyzed by evaluating immune
      parameters in the plasma. Additionally, ultrastructural characteristics of the
      inner epithelium of the brood pouch were compared between males that had
      experienced mating failure and those that had succeeded. Generally, immunity in
      sexually mature virgin males was greater than in females, and mating competition
      significantly reduced males' immunity. However, parental care gave males stronger
      immune and metabolic abilities and resulted in their immunity significantly
      rebounding after a successful mating. The present study quantitatively clarifies,
      for the first time, how parental care and mating competition jointly affect
      immunity. Moreover, previous findings that females display more efficient immune
      defenses than males in conventional species (i.e., males are as competitor and
      females as care giver) and that males' immunity is higher than females' in the
      pipefish (i.e., females are as competitor and males as care giver) in combination
      with the present results indicate that parental care is a key factor for sexual
      dimorphism in immunity. The care-giving sex has strong immunity regardless of the
      sex in charge of mating competition or not.

PMID- 27702677
TI  - Immune reactivity in early life stages of sea-cage cultured Pacific bluefin tuna
      naturally infected with blood flukes from genus Cardicola (Trematoda:
      Aporocotylidae).
AB  - Pacific bluefin tuna (PBT), Thunnus orientalis, due to its high average price on
      the market is an economically valuable fish species. Infections by blood flukes
      from the genus Cardicola (Trematoda: Aporocotylidae) represent a growing concern
      for the cage culture of bluefin tuna in Japan, Australia and Southern Europe. The
      accumulation of numerous Cardicola eggs in the fish gills causes severe pathology
      that has been linked to mortality in PBT juveniles up to one year old. The only
      effective treatment used to mitigate the infection is the oral administration of
      the antihelminthic drug praziquantel (PZQ) to the affected fish. However, with
      the need to minimise therapeutic drug use in aquaculture it is hoped that
      immunoprophylaxis can provide a future alternative to protect the PBT juveniles
      against Cardicola infection. Currently, little is known of the host immune
      response to these parasites and of their infection dynamics. In this study, using
      real-time qPCR we aimed to quantitatively detect C. orientalis and C.
      opisthorchis DNA within the gills and heart of cultured PBT juveniles and to
      investigate the host immune response at the transcriptional level in the gills.
      The research focused mainly during early stages of infection soon after young PBT
      were transferred to culture cages (from 14 to 77 days post-transfer). An increase
      (up to 11-fold) of immune-related genes, namely IgM, MHC-I, TCR-beta and IL-1beta
      was observed in the PBT gills infected with Cardicola spp. (28-77 days post
      transfer). Furthermore, IgM (19-fold increase) and MHC-I (11.5-fold increase)
      transcription was strongly up-regulated in gill samples of PBT infected with C.
      orientalis relative to uninfected fish but not in fish infected with C.
      opisthorchis. Cardicola-specific DNA was first detected in the host 14 days post
      transfer (DPT) to sea-cages which was 55 days earlier than the first detection of
      parasite eggs and adults by microscopy. Oral administration of PZQ did not have
      an immediate effect on parasite DNA presence in the host and the DNA presence
      started to reduce after 24 days only in the host heart. The results provide
      evidence of an immune response in early age sea-cage cultured juveniles of PBT
      naturally infected with C. orientalis and C. opisthorchis. This response, whilst
      not protective against primary infection, provides evidence that immunisation at
      an early age may have potential as a health strategy.

PMID- 27702679
TI  - Characterization of IgM in Norwegian cleaner fish (lumpfish and wrasses).
AB  - The use of cleaner fish in Norwegian aquaculture has to a large extent been based
      on wild catches, but breeding of lumpfish and ballan wrasse is currently
      increasing. Due to disease problems and required vaccine development, tools to
      study immune responses and a better understanding of the immune system in these
      species is demanded. The present study comprises lumpfish (Cyclopterus lumpus)
      and five species of wrasses: Ballan wrasse (Labrus bergylta), rock cook
      (Centrolabrus exoletus), cuckoo wrasse (Labrus mixtus), corkwing wrasse
      (Symphodus melops), and goldsinny wrasse (Ctenolabrus rupestris). We present a
      comparison of the IgM sequences, phylogenetic relationship to other teleosts and
      characteristic features of IgM in the species studied. The lumpfish IgM heavy
      chain sequence was assembled from high throughput cDNA sequencing whereas the
      wrasse sequences were determined by molecular cloning. The secreted form of the
      IgM heavy chain from all species consisted of four constant Ig domains. IgM was
      purified from lumpfish and ballan wrasse sera by gel filtration followed by anion
      exchange chromatography, and polyclonal sera were produced against these
      proteins. Antisera against ballan wrasse IgM showed cross-reactivity to all
      analyzed species of wrasses, some cross-reactivity to lumpfish, very low reaction
      to salmon, and no reaction to cod. Anti- IgM sera against lumpfish cross-reacted
      to the light chain of all species studied. Wrasses and lumpfish IgM showed high
      binding affinities for protein A. IgM concentration in adult ballan wrasse (700
      800 g) was measured by single radial immunodiffusion assay and found to be 13.4
      mg/ml which is about 36% of the total protein concentration. The IgM
      concentration in lumpfish (600-3600 g) was estimated to 1-2.6 mg/ml, which
      corresponds to approximately 3% of the total protein concentration.

PMID- 27702680
TI  - Response to the questions submitted by Mr. Reichmann.

PMID- 27702681
TI  - Targeting the complex interactions between microbiota, host epithelial and immune
      cells in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder
      that includes two distinct disease categories: ulcerative colitis and Crohn's
      disease. Epidemiological, genetic, and experimental studies have revealed many
      important aspects of IBD. Genetic susceptibility, inappropriate immune responses,
      environmental changes, and intestinal microbiota are all associated with the
      development of IBD. However, the exact mechanisms of the disease and the
      interactions among these pathogenic factors are largely unknown. Here we
      introduce recent findings from experimental colitis models that investigated the
      interactions between host genetic susceptibility and gut microbiota. In addition,
      we discuss new strategies for the treatment of IBD, focusing on the complex
      interactions between microbiota and host epithelial and immune cells.

PMID- 27702682
TI  - Perinatal programming of depressive-like behavior by inflammation in adult
      offspring mice whose mothers were fed polluted eels: Gender selective effects.
AB  - Several lines of evidence indicate that early-life inflammation may predispose to
      mental illness, including depression, in later-life. We investigated the impact
      of perinatal exposure to polluted eels on neonatal, postnatal, and adult brain
      inflammation, and on the resignation behavior of male and female adult offspring
      mice. The effects of maternal standard diet (laboratory food) were compared to
      the same diet enriched with low, intermediate, or highly polluted eels. Brain
      inflammatory markers including cytokines were assessed in offspring mice on the
      day of birth (i.e., on the postnatal day-PND 1), upon weaning (PND 21) and at
      adulthood (PND 100). Plasma myeloperoxidase and corticosterone levels were
      evaluated at PND 100. Immobility behavior of offspring was assessed in adulthood
      (i.e., at PNDs 95-100), using the tail suspension and forced swimming tests.
      Chronic brain inflammation was found in male and female offspring mice compared
      to controls, as assessed at PNDs 1, 21, and 100. The level of myeloperoxidase was
      found to be significantly higher in both adult males and females vs. control
      offspring. However, high corticosterone levels were only found in male offspring
      mice that were perinatally exposed to eels, suggesting a gender-selective
      dysregulation of the adult hypothalamic-pituitaryadrenal (HPA) axis. Gender
      specific differences were also detected in adulthood in regard to offspring
      resignation behavior. Thus, compared to controls, males, but not females, whose
      mothers were fed eels during pregnancy and lactation exhibited a depressive-like
      behavior in adult age in both behavioral models of depression. Depressive
      symptoms were more pronounced in male mice perinatally exposed to either
      intermediate or highly polluted eels than those exposed to only lowly polluted
      eels. Our results indicate that early-life inflammatory insult is a plausible
      causative factor that induces the depressive phenotype exhibited by male adult
      offspring mice, most likely through a gender-specific HPA axis enhanced
      activation.

PMID- 27702683
TI  - Trends of the microcephaly and Zika virus outbreak in Brazil, January-July 2016.
AB  - In the last two months, there have been indications that the Zika virus epidemic
      is on the decline in Brazil. We reviewed the surveillance data published by the
      Brazilian Ministry of Health to assess trends of microcephaly and neurological
      abnormalities suggestive of congenital infection, as well as Zika virus disease
      in Brazil as a whole and its various regions. From November 2015 to July 2016,
      8301 cases of microcephaly were reported in Brazil, mainly in the Northeast
      region. The number of newly reported cases is declining throughout the country,
      except in the Southeast region. The numbers of cases that remain under
      investigation still represent 37.7% of all reported cases in early July.
      Meanwhile, from January to June, 2016, 165,241 cases of Zika virus disease were
      reported in Brazil. The state of Rio de Janeiro (Southeast) experienced the third
      highest incidence, lagging behind only the states of Bahia (Northeast) and Mato
      Grosso (Midwest). In early June, the number of new Zika virus cases showed a
      marked decline in all of the regions, except the North. Although the Zika
      epidemic seems to be diminishing, continued monitoring and surveillance of
      reported microcephaly and neurological abnormality cases is essential, and
      investigation efforts need to be vastly improved, as some states still reported
      high incidences of Zika disease in the first half of 2016.

PMID- 27702684
TI  - Lipopeptide-based micellar and liposomal carriers: Influence of surface charge
      and particle size on cellular uptake into blood brain barrier cells.
AB  - Lipopeptide-based micelles and liposomes were found to differ in cell recognition
      and uptake mode into blood brain barrier (BBB) endothelial cells. Here we analyse
      the role of size and surface charge of micelles and liposomes composed of
      different lipopeptide sequences with respect to uptake into human brain capillary
      (HBMEC) and aortic (HAoEC) endothelial cells. Comparable to the dipalmitoylated
      apolipoprotein E-derived P2A2, lipopeptides of cationic poly-arginine (P2Rn),
      poly-lysine (P2Kn) and an anionic glutamic-acid sequence (P2En) self assemble
      into micelles (12-14nm in diameter) with high surface charge density, and bind to
      small (SUVs, about 24nm in diameter) and large (LUV, about 100nm in diameter)
      liposomes at variable lipid to peptide ratios. The interaction pattern of the
      resulting particles with endothelial cells is highly variable as revealed by
      confocal laser scanning microscopic (CLSM) and fluorescence assisted cell sorting
      (FACS) studies. Micelles and SUVs with high P2A2 density are efficiently and
      selectively internalized into HBMEC. P2Kn micelles strongly accumulate in both
      the cytosol and at the cell membrane, while the interaction of liposomes tagged
      with a low amount of P2A2 and P2Kn with the cells was reduced. Anionic micelles
      seem to dissociate in the presence of cells and P2En molecules incorporate into
      the cellular membrane whereas the negatively charged liposomes hardly interact
      with cells. Surprisingly, all poly-R-based particles show high selectivity for
      HBMEC compared to HAoEC, independent of particle size and peptide surface
      density. The P2Rn-mediated internalization is highly efficient and partially
      clathrin-dependent. The oligo-R lipopeptide is considered to be most promising to
      selectively transport different drug carriers into the blood brain barrier.

PMID- 27702685
TI  - Conjugates of HA2 with octaarginine-grafted HPMA copolymer offer effective siRNA
      delivery and gene silencing in cancer cells.
AB  - The key for successful gene silencing is to design a safe and efficient siRNA
      delivery system for the transfer of therapeutic nucleic acids into the target
      cells. Here, we describe the design of hydrophilic N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymer displaying multiple copies of
      octaarginine (R8) and its use in promoting the effective delivery of small
      interfering RNA (siRNA) molecules intracellularly. Fluorescein-5-isothiocyanate
      (FITC)-labeled HPMA copolymer-bound R8 (P-R8-FITC) was synthesized with
      increasing R8 molar ratios (4-9.5mol-%) to define the optimal R8 content that
      allowed the polymer to serve both as a siRNA-binding domain and as an
      intracellular transduction moiety mediating improved cellular delivery. A subunit
      of the influenza virus hemagglutinin (HA2), known for its ability to disrupt
      endosomal membranes, was further conjugated to P-R8-FITC copolymer to promote
      endosomal escape. Of the different P-(R8)-FITC conjugates considered, only that
      polymer containing the highest mol-% of R8 (P-(R8)9.5-FITC) was able to
      encapsulate siRNA molecules into nano-sized polyion complexes (PICs) presenting
      positive surface charge, low in vitro cytotoxicity, and high serum stability. P
      (R8)9.5-FITC/cy5-siRNA complexes can efficiently deliver siRNA molecules into
      cells, while naked siRNA or siRNA encapsulated within polymers with lower R8mol-%
      were unable to transfect the same cells. Conjugation of HA2 fusogenic peptide to
      P-(R8)-FITC significantly decreased the oncogenic RAC1 mRNA levels in cancer
      cells. This indicates that P-(R8)-(HA2)-FITC can deliver siRNA into target cells,
      and that the siRNA can reach the perinuclear region where it interacts with the
      RNA-induced silencing complex.

PMID- 27702686
TI  - Inhibition of carbonic anhydrase IX in glioblastoma multiforme.
AB  - Carbonic anhydrase IX (CAIX) is a transmembrane enzyme upregulated in several
      types of tumors including glioblastoma multiforme (GBM). GBM is among the most
      aggressive tumors among gliomas. Temozolomide (TMZ) therapy combined with
      surgical or radiation approaches is the standard treatment but not effective in
      long term. In this study we tested the treatment with acetazolamide (ATZ), an
      inhibitor of CAIX, alone or combined with TMZ. The experiments were performed in
      2D and 3D cultures (spheroids) using glioblastoma U251N and human brain tumor
      stem cells (BTSCs). Several proteins implicated in tumor cell death were also
      investigated. The key results from these studies suggest the following: (1) Cell
      death of human glioblastoma spheroids and BTSC is significantly increased with
      combined treatment after 7 days, and (2) the effectiveness of ATZ is
      significantly enhanced against BTSC and U251N when incorporated into nano
      carriers. Collectively, these results point toward the usefulness of nano
      delivery of CAIX inhibitors and their combination with chemotherapeutics for
      glioblastoma treatment.

PMID- 27702687
TI  - Innovative drug vehicle for local treatment of inflammatory skin diseases: Ex
      vivo and in vivo screening of five topical formulations containing poly(lactic
      acid) (PLA) nanoparticles.
AB  - One of the main goals in the galenic development of innovative topical treatment
      options for inflammatory skin diseases such as psoriasis and atopic dermatitis is
      to selectively deliver the drug at the inflammation site. Recent studies have
      highlighted the beneficial use of polymeric nanoparticles for anti-inflammatory
      therapy and topical anti-inflammatory drug delivery due to their ability to form
      a drug reservoir retaining the drug locally at the site of action. Our approach
      consisted in designing innovative topical semi-solid formulations of poly(lactic
      acid) (PLA) nanoparticles as anti-inflammatory drug vehicles for local treatment
      of inflammatory skin diseases. In the course of this work, five topical
      formulations containing fluorescent PLA nanoparticles were initially developed,
      and then screened depending on their physico-chemical properties, toxicity and
      delivery efficacy. The penetration and permeation of a fluorophore vectorized by
      PLA nanoparticles into healthy and inflammatory skin were assessed using an
      alternative device to classical Franz cells: VitroPharma. All these
      investigations led to the selection of two satisfactory formulations out of five
      initial candidates.

PMID- 27702688
TI  - Performance of several Saccharomyces strains for the alcoholic fermentation of
      sugar-sweetened high-strength wastewaters: Comparative analysis and kinetic
      modelling.
AB  - This work focuses on the performance of ten commercial Saccharomyces yeast
      strains in the batch alcoholic fermentation of sugars contained in selected
      industrial wastewaters from the soft drink industry. Fermentation has been
      applied successfully to treat these effluents prior to their disposal. Although
      many strains were investigated, similar behaviour was observed between all of the
      Saccharomyces strains tested. When media were inoculated with 2gL-1 of yeast, all
      strains were able to completely consume the available sugars in less than 14h.
      Thus, any of the strains studied in this work could be used in non-conventional
      wastewater treatment processes based on alcoholic fermentation. However, ethanol
      production varied between strains, and these differences could be significant
      from a production point of view. Saccharomyces bayanus produced the most ethanol,
      with a mean yield of 0.44gethanolgsugarconsumed-1 and an ethanol specific
      production rate of 5.96gethanol (Lh)-1. As the assayed soft drinks wastewaters
      contain about 105gsugar/L of fermentable sugars, the concentration of ethanol
      achieved after the fermentations process was 46.2gethanol/L. A rigorous kinetic
      modelling methodology was used to model the Saccharomyces bayanus fermentation
      process. The kinetic model included coupled mass balances and a minimal number of
      parameters. A simple unstructured model based on the Andrews equation (substrate
      inhibition) was developed. This model satisfactorily described biomass growth,
      sugar consumption and bioethanol production. In addition to providing insights
      into the fermentative performance of potentially relevant strains, this work can
      facilitate the design of large-scale ethanol production processes that use
      wastewaters from the sugar-sweetened beverage industry as feedstock.

PMID- 27702690
TI  - Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of
      four major active diterpenoids after multiple oral dose administration in healthy
      Thai volunteers.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata is included in 'The
      National List of Essential Herbal Drugs A.D. 1999' of Thailand as an herbal drug
      for the treatment of common cold symptoms and non-infectious diarrhea. The
      therapeutic activities of A. paniculata are attributed to four major active
      diterpenoids: andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2),
      neoandrographolide (3), and 14-deoxyandrographolide (4). However, the
      pharmacokinetic studies in humans of this plant were performed after a single
      oral dose administration and reported the parameters related to be of only 1. AIM
      OF THE STUDY: This study aims to determine the pharmacokinetic parameters of four
      major active diterpenoids after multiple oral dose administration of A.
      paniculata capsules in healthy volunteers. The dissolution testing of these four
      diterpenoids was also performed. MATERIALS AND METHOD: The dissolution testing of
      four major active diterpenoids was conducted in pH 1.2, pH 4.5, and pH 6.8 for 10
      100min. The pharmacokinetic study of these active diterpenoids was designed as an
      open-label, multiple oral dose administration of A. paniculata capsules in 20
      healthy Thai volunteers at 1:1 ratio of female and male. Each volunteer was given
      four A. paniculata capsules each time which contained 1, 2, 3, and 4 in the
      quantities of 32.64, 5.40, 3.60, and 3.84mg, respectively, three times a day for
      three consecutive days. On the fourth day, after the first dose of the day was
      administered, blood samples were collected at the predefined time points. The
      validated LC-MS/MS method was used to simultaneously determine the concentrations
      of these diterpenoids in the human plasma samples. The pharmacokinetic parameters
      of each active diterpenoid were determined. RESULTS: All four major active
      diterpenoids have been completely dissolved in the simulated pH of
      gastrointestinal tract within 60min of dissolution. The dissolution profiles were
      found to be highest in pH 6.8 and lowest in pH 1.2, especially for 3. In the
      pharmacokinetic study, although 1 was administered at the highest dose among
      these four diterpenoids, 2 exhibited the highest maximum concentrations (Cmax) of
      44.89ng/mL and area under the plasma concentration-time curve (AUC) of
      128.17h*ng/mL. Compound 1 had the second highest Cmax and AUC as 32.41ng/mL and
      55.23h*ng/mL, respectively. The relative systemic exposure, represented by the
      dose normalized AUC [(h*ng/mL)/(mg/kg)], of 2 was approximately 14 times higher
      than that of 1, while those of 3 and 4 were approximately 1.5 and 1.6 times
      higher, respectively. Cmax, AUC, apparent volume of distribution, and apparent
      clearance of 2 were found to be significant difference between female and male.
      However, when these parameters were calculated as dose normalized basis, no
      statistically significant difference was found. CONCLUSION: The four major active
      diterpenoids in the A. paniculata capsules were soluble in all studied
      dissolution media. The pharmacokinetic parameters of these active diterpenoids in
      the present study could be applied for dose optimization of A. paniculata product
      in order to obtain good therapeutic efficacy and reduce the possible side effects
      that may occur from different active diterpenoids in this medicinal plant.

PMID- 27702689
TI  - Screening of soluble epoxide hydrolase inhibitory ingredients from traditional
      Chinese medicines for anti-inflammatory use.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Inhibition of soluble epoxide hydrolase (sEH) has
      been extensively reported to be anti-inflammatory in multiple animal models. Some
      anti-inflammatory traditional Chinese medicines (TCMs) and a few natural
      compounds were also found to be inhibitory to sEH in vitro. AIM OF THE STUDY: To
      determine whether the active intergradient (AI) against sEH of anti-inflammatory
      TCMs in vitro is anti-inflammatory in vivo and the sEH inhibitory action of the
      AI contributes to its anti-inflammatory effect in vivo. MATERIALS AND METHODS: In
      vitro inhibition assay of the sEH was conducted for the methanol and ethanol
      extracts of 27 anti-inflammatory TCMs. Two potent extracts were subject to
      further separation guided by bioassay to afford promising AI against sEH in vitro
      [Fr.5 of the crude ethanol extract of Rhizoma coptidis (FFCERC)]. Finally, the in
      vivo anti-inflammatory effect and sEH inhibitory potency of FFCERC was evaluated
      in a lipopolysacchride (LPS)-challenged murine model of acute systemic
      inflammation. The inflammatory status was characterized by the inflammatory
      cytokines TNF-alpha and interleukin-6 (IL-6) and sEH inhibitory function was
      evaluated by the plasma levels of epoxyeicosantrienoic acids (EETs) and
      dihydroxyeicosatrienoic acids (DHETs), which are the sEH mediated substrates and
      products, respectively. RESULTS: At the concentration of 25ug/mL, the crude
      ethanol extracts of 6 TCMs including Herba Asari, Radix Polygalae, Fructus Amomi,
      Radix Astragali, Radix Scutellariae, and Rhizoma Coptidis were potent against
      sEH. The crude extracts of Herba Asari and Rhizoma Coptidis were selected for
      further separation to afford FFCERC as the most promising AI for in vivo
      evaluation. Oral administration of FFCERC attenuated the significant increase in
      TNF-alpha and IL-6 caused by LPS challenge in a dose-dependent manner. In
      parallel, oral administration of FFCERC shifted the changes in plasma levels of
      EETs and DHETs caused by LPS-challenge like a synthetic sEH inhibitor.
      CONCLUSIONS: A sEH inhibitory AI from Rhizoma Coptidis is anti-inflammatory and
      the inhibition of sEH contributes to this biological effect, indicating that sEH
      may be at least one of multiple therapeutic targets for relevant TCMs.

PMID- 27702692
TI  - The High Light Response and Redox Control of Thylakoid FtsH Protease in
      Chlamydomonas reinhardtii.
AB  - In Chlamydomonas reinhardtii, the major protease involved in the maintenance of
      photosynthetic machinery in thylakoid membranes, the FtsH protease, mostly forms
      large hetero-oligomers (~1 MDa) comprising FtsH1 and FtsH2 subunits, whatever the
      light intensity for growth. Upon high light exposure, the FtsH subunits display a
      shorter half-life, which is counterbalanced by an increase in FTSH1/2 mRNA
      levels, resulting in the modest upregulation of FtsH1/2 proteins. Furthermore, we
      found that high light increases the protease activity through a hitherto
      unnoticed redox-controlled reduction of intermolecular disulfide bridges. We
      isolated a Chlamydomonas FTSH1 promoter-deficient mutant, ftsh1-3, resulting from
      the insertion of a TOC1 transposon, in which the high light-induced upregulation
      of FTSH1 gene expression is largely lost. In ftsh1-3, the abundance of FtsH1 and
      FtsH2 proteins are loosely coupled (decreased by 70% and 30%, respectively) with
      no formation of large and stable homo-oligomers. Using strains exhibiting
      different accumulation levels of the FtsH1 subunit after complementation of ftsh1
      3, we demonstrate that high light tolerance is tightly correlated with the
      abundance of the FtsH protease. Thus, the response of Chlamydomonas to light
      stress involves higher levels of FtsH1/2 subunits associated into large complexes
      with increased proteolytic activity.

PMID- 27702691
TI  - Targeting acid sphingomyelinase with anti-angiogenic chemotherapy.
AB  - Despite great promise, combining anti-angiogenic and conventional anti-cancer
      drugs has produced limited therapeutic benefit in clinical trials, presumably
      because mechanisms of anti-angiogenic tissue response remain only partially
      understood. Here we define a new paradigm, in which anti-angiogenic drugs can be
      used to chemosensitize tumors by targeting the endothelial acid sphingomyelinase
      (ASMase) signal transduction pathway. We demonstrate that paclitaxel and
      etoposide, but not cisplatin, confer ASMase-mediated endothelial injury within
      minutes. This rapid reaction is required for human HCT-116 colon cancer xenograft
      complete response and growth delay. Whereas VEGF inhibits ASMase, anti-VEGFR2
      antibodies de-repress ASMase, enhancing endothelial apoptosis and drug-induced
      tumor response in asmase+/+, but not in asmase-/-, hosts. Such chemosensitization
      occurs only if the anti-angiogenic drug is delivered 1-2h before chemotherapy,
      but at no other time prior to or post chemotherapy. Our studies suggest that
      precisely-timed administration of anti-angiogenic drugs in combination with
      ASMase-targeting anti-cancer drugs is likely to optimize anti-tumor effects of
      systemic chemotherapy. This strategy warrants evaluation in future clinical
      trials.

PMID- 27702693
TI  - Photorespiration Is Crucial for Dynamic Response of Photosynthetic Metabolism and
      Stomatal Movement to Altered CO2 Availability.
AB  - The photorespiratory pathway or photorespiration is an essential process in
      oxygenic photosynthetic organisms, which can reduce the efficiency of
      photosynthetic carbon assimilation and is hence frequently considered as a
      wasteful process. By comparing the response of the wild-type plants and mutants
      impaired in photorespiration to a shift in ambient CO2 concentrations, we
      demonstrate that photorespiration also plays a beneficial role during short-term
      acclimation to reduced CO2 availability. The wild-type plants responded with few
      differentially expressed genes, mostly involved in drought stress, which is
      likely a consequence of enhanced opening of stomata and concomitant water loss
      upon a shift toward low CO2. In contrast, mutants with impaired activity of
      photorespiratory enzymes were highly stressed and not able to adjust stomatal
      conductance to reduced external CO2 availability. The transcriptional response of
      mutant plants was congruent, indicating a general reprogramming to deal with the
      consequences of reduced CO2 availability, signaled by enhanced oxygenation of
      ribulose-1,5-bisphosphate and amplified by the artificially impaired
      photorespiratory metabolism. Central in this reprogramming was the pronounced
      reallocation of resources from growth processes to stress responses. Taken
      together, our results indicate that unrestricted photorespiratory metabolism is a
      prerequisite for rapid physiological acclimation to a reduction in CO2
      availability.

PMID- 27702694
TI  - Thoracic Endovascular Aortic Repair for Embolizing Total Occlusion of the
      Descending Aorta due to Aortic Sarcoma.
AB  - Primary malignant tumors of the aorta are extremely rare, and the diagnosis is
      difficult from the clinical onset. Accordingly to the principles of cancer
      surgery, "en bloc" resection of the tumor-involved aorta and graft interposition
      is the gold standard, but it is still technically challenging and comorbidities
      may rule out some patients from an operative treatment. Thoracic endovascular
      aortic repair has been reported anecdotally, but it is an ease and rapid
      alternative in urgent circumstances and proved to be effective to relieve
      symptoms caused by these lesions. Unfortunately, no matter what is the type of
      histology or immunohistochemistry, or the type of treatment, the prognosis of
      aortic malignancies is very poor. Nevertheless, an operative treatment strategy
      which includes surgical resection and chemotherapy or radiation had long survival
      than patients treated with a single modality. We report a case of acute
      mesenteric syndrome caused by an occlusive and embolizing thrombus of the
      descending thoracic aorta caused by primary aortic sarcoma treated with thoracic
      endovascular aortic repair.

PMID- 27702695
TI  - Multispectral UV imaging for surface analysis of MUPS tablets with special focus
      on the pellet distribution.
AB  - In the present study the applicability of multispectral UV imaging in combination
      with multivariate image analysis for surface evaluation of MUPS tablets was
      investigated with respect to the differentiation of the API pellets from the
      excipients matrix, estimation of the drug content as well as pellet distribution,
      and influence of the coating material and tablet thickness on the predictive
      model. Different formulations consisting of coated drug pellets with two coating
      polymers (Aquacoat(r) ECD and Eudragit(r) NE 30 D) at three coating levels each
      were compressed to MUPS tablets with various amounts of coated pellets and
      different tablet thicknesses. The coated drug pellets were clearly
      distinguishable from the excipients matrix using a partial least squares approach
      regardless of the coating layer thickness and coating material used. Furthermore,
      the number of the detected drug pellets on the tablet surface allowed an
      estimation of the true drug content in the respective MUPS tablet. In addition,
      the pellet distribution in the MUPS formulations could be estimated by UV image
      analysis of the tablet surface. In conclusion, this study revealed that UV
      imaging in combination with multivariate image analysis is a promising approach
      for the automatic quality control of MUPS tablets during the manufacturing
      process.

PMID- 27702696
TI  - Reevaluation of the diametral compression test for tablets using the flattened
      disc geometry.
AB  - Mechanical strength is an important critical quality attribute for tablets. It is
      classically measured, in the pharmaceutical field, using the diametral
      compression test. Nevertheless, due to small contact area between the tablet and
      the platens, some authors suggested that during the test, the failure could occur
      in tension away from the center which would invalidate the test and the
      calculation of the tensile strength. In this study, the flattened disc geometry
      was used as an alternative to avoid contact problems. The diametral compression
      on both flattened and standard geometries was first studied using finite element
      method (FEM) simulation. It was found that, for the flattened geometry, both
      maximum tensile strain and stress were located at the center of the tablet, which
      was not the case for the standard geometry. Experimental observations using
      digital image correlation (DIC) confirmed the numerical results. The experimental
      tensile strength obtained using both geometries were compared and it was found
      that the standard geometry always gave lower tensile strength than the flattened
      geometry. Finally, high-speed video capture of the test made it possible to
      detect that for the standard geometry the crack initiation was always away from
      the center of the tablet.

PMID- 27702697
TI  - Application of RPMI 2650 as a cell model to evaluate solid formulations for
      intranasal delivery of drugs.
AB  - During the development of intranasal drug delivery systems for local/systemic
      effect or brain targeting, it is necessary to assess its cytotoxicity and drug
      transport through nasal epithelium. In order to avoid animal experiments or the
      use of excised tissues, in vitro cell models, such as RPMI 2650 cells, are being
      preferred during recent years. Nevertheless, the deposition of solid formulations
      into nasal cell layers with further transepithelial transport rate of drugs has
      been poorly studied or reported. Thus, the purpose of this work is to further
      investigate RPMI 2650 cell line as an effective alternative to animal tissues for
      solid drug-loaded formulations cytotoxicity and drug permeation studies in order
      to become an option as a tool for drug discovery. Furthermore, we wanted to
      determine the extent to which the administration of drugs in particulate forms
      would differ in relation to the permeability of the same compounds applied as
      solutions. RPMI 2650 cells were cultured in submersed or at air-liquid interface
      conditions and characterized regarding transepithelial electrical resistance
      (TEER) and production of mucus. Pure ketoprofen (used as model compound) and five
      formulations loaded with same drug, namely solid lipid particles (Gelucire
      43/01TM), structured lipid particles (Gelucire 43/01TM:Glyceryl monooleate) and
      aerogel microparticles (Alginate, Alginate:Pectin, Alginate:Carrageenan), were
      evaluated with RPMI 2650 model in terms of cytotoxicity and permeability of drug
      (applied as solution, dispersion or powder+buffer). RPMI 2650 cells were capable
      to grow in monolayer and multilayer, showing the same permeability as excised
      human nasal mucosa for sodium fluorescein (paracellular marker), with analogous
      TEER values and production of mucus, as referred by other authors. None of the
      powders showed cytotoxicity when applied to RPMI 2650 cells. Regarding permeation
      of drug through cell layers, not only the form of application of powders but also
      their physical and chemical properties affected the final permeation of active
      pharmaceutical ingredient. Aerogel microparticles administered directly to the
      cell layer (powder+buffer) exhibited the highest permeation-enhancing effect
      compared to the pure drug, which can be attributed to the mucoadhesive properties
      of the materials composing the carriers, proving to be an attractive formulation
      for nasal drug delivery. According to these results, RPMI 2650 showed to be a
      promising alternative to ex vivo or in vivo nasal models for cytotoxicity and
      evaluation of drug permeability of nasal drug-loaded formulations.

PMID- 27702699
TI  - Targeting chaperones, heat shock factor-1, and unfolded protein response:
      Promising therapeutic approaches for neurodegenerative disorders.
AB  - Protein misfolding, which is known to cause several serious diseases, is an
      emerging field that addresses multiple therapeutic areas. Misfolding of a disease
      specific protein in the central nervous system ultimately results in the
      formation of toxic aggregates that may accumulate in the brain, leading to
      neuronal cell death and dysfunction, and associated clinical manifestations. A
      large number of neurodegenerative diseases in humans, including Alzheimer's,
      Parkinson's, Huntington's, and prion diseases, are primarily caused by protein
      misfolding and aggregation. Notably, the cellular system is equipped with a
      protein quality control system encompassing chaperones, ubiquitin proteasome
      system, and autophagy, as a defense mechanism that monitors protein folding and
      eliminates inappropriately folded proteins. As the intrinsic molecular mechanisms
      of protein misfolding become more clearly understood, the novel therapeutic
      approaches in this arena are gaining considerable interest. The present review
      will describe the chaperones network and different approaches as the therapeutic
      targets for neurodegenerative diseases. Current and emerging therapeutic
      approaches to combat neurodegenerative diseases, addressing the roles of
      molecular, chemical, and pharmacological chaperones, as well as heat shock factor
      1 and the unfolded protein response, are also discussed in detail.

PMID- 27702700
TI  - Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated
      adipose tissue and skeletal muscle inflammation as a main mechanism of the
      pathogenesis.
AB  - Sarcopenia, an age-associated decline in skeletal muscle mass coupled with
      functional deterioration, may be exacerbated by obesity leading to higher
      disability, frailty, morbidity and mortality rates. In the combination of
      sarcopenia and obesity, the state called sarcopenic obesity (SOB), some key age-
      and obesity-mediated factors and pathways may aggravate sarcopenia. This review
      will analyze the mechanisms underlying the pathogenesis of SOB. In obese adipose
      tissue (AT), adipocytes undergo hypertrophy, hyperplasia and activation resulted
      in accumulation of pro-inflammatory macrophages and other immune cells as well as
      dysregulated production of various adipokines that together with senescent cells
      and the immune cell-released cytokines and chemokines create a local pro
      inflammatory status. In addition, obese AT is characterized by excessive
      production and disturbed capacity to store lipids, which accumulate ectopically
      in skeletal muscle. These intramuscular lipids and their derivatives induce
      mitochondrial dysfunction characterized by impaired beta-oxidation capacity and
      increased reactive oxygen species formation providing lipotoxic environment and
      insulin resistance as well as enhanced secretion of some pro-inflammatory
      myokines capable of inducing muscle dysfunction by auto/paracrine manner. In
      turn, by endocrine manner, these myokines may exacerbate AT inflammation and also
      support chronic low grade systemic inflammation (inflammaging), overall
      establishing a detrimental vicious circle maintaining AT and skeletal muscle
      inflammation, thus triggering and supporting SOB development. Under these
      circumstances, we believe that AT inflammation dominates over skeletal muscle
      inflammation. Thus, in essence, it redirects the vector of processes from
      "sarcopenia->obesity" to "obesity->sarcopenia". We therefore propose that this
      condition be defined as "obese sarcopenia", to reflect the direction of the
      pathological pathway.

PMID- 27702701
TI  - The Effect of Vertical Versus Horizontal Vaginal Cuff Closure on Vaginal Length
      After Laparoscopic Hysterectomy.
AB  - : STUDY OBJECTIVE: To determine whether vertical versus horizontal closure of the
      vaginal cuff during laparoscopic hysterectomy has an effect on postoperative
      vaginal length and pelvic organ prolapse. DESIGN: A prospective randomized
      controlled trial. Subjects were randomly assigned to vertical or horizontal
      vaginal cuff closure at the time of total laparoscopic hysterectomy. Pelvic organ
      prolapse quantization (POP-Q) tests were performed before surgery, 2 to 4 weeks
      after surgery, and 3 to 4 months after surgery (Canadian Task Force
      classification I). SETTING: An academic university-affiliated community hospital.
      PATIENTS: Patients undergoing laparoscopic or robotic-assisted laparoscopic total
      hysterectomy for benign or malignant disease, excluding those undergoing radical
      hysterectomy or concomitant pelvic floor procedure. INTERVENTIONS: Subjects were
      randomized into the vertical or horizontal vaginal cuff closure group. Total
      hysterectomy was completed with traditional laparoscopic techniques or with
      robotic assistance. A colpotomy ring was used in each subject. Vaginal cuff
      closure was performed with barbed suture in a running fashion according to the
      group assignment. MEASUREMENTS AND MAIN RESULTS: A total of 43 subjects were
      enrolled and randomized. One patient was excluded because the vaginal cuff was
      closed vaginally, 1 cancelled surgery, and 1 was completed without a uterine
      manipulator. The mean change in vaginal length was -0.89 cm (standard deviation
      [SD] = 1.03) in the horizontal group and -0.86 cm (SD = 1.19) in the vertical
      group (p = .57). POP-Q evaluation revealed no differences between groups and an
      overall trend toward improved POP-Q measurements. The average duration of vaginal
      cuff closure did not differ (p = .45), and there were no intraoperative
      complications related to vaginal cuff closure. CONCLUSION: Horizontal and
      vertical laparoscopic closure of the vaginal cuff after laparoscopic hysterectomy
      results in similar changes in vaginal length and other POP-Q scores.

PMID- 27702698
TI  - Life and death in the trash heap: The ubiquitin proteasome pathway and UCHL1 in
      brain aging, neurodegenerative disease and cerebral Ischemia.
AB  - The ubiquitin proteasome pathway (UPP) is essential for removing abnormal
      proteins and preventing accumulation of potentially toxic proteins within the
      neuron. UPP dysfunction occurs with normal aging and is associated with abnormal
      accumulation of protein aggregates within neurons in neurodegenerative diseases.
      Ischemia disrupts UPP function and thus may contribute to UPP dysfunction seen in
      the aging brain and in neurodegenerative diseases. Ubiquitin carboxy-terminal
      hydrolase L1 (UCHL1), an important component of the UPP in the neuron, is
      covalently modified and its activity inhibited by reactive lipids produced after
      ischemia. As a result, degradation of toxic proteins is impaired which may
      exacerbate neuronal function and cell death in stroke and neurodegenerative
      diseases. Preserving or restoring UCHL1 activity may be an effective therapeutic
      strategy in stroke and neurodegenerative diseases.

PMID- 27702702
TI  - Temporarily Blocking the Uterine Artery to Dig Out a Diffused Adenomyosis Lesion
      Treated Laparoscopically.
AB  - STUDY OBJECTIVE: To show the tips and tricks of a simpler technique for temporary
      blocking of the uterine artery in laparoscopic resection of a diffuse adenomyosis
      lesion to make the procedure more efficient and reproducible. DESIGN: This study
      is designed to be a step-by-step explanation of the technique using videos and
      pictures (Canadian Task Force classification III). SETTING: Changzhou Maternal
      and Child Health Hospital, Changzhou, China. PATIENTS: Three patients (age 39-42
      years, 41+/-1.73) were diagnosed with diffuse adenomyosis with severe secondary
      dysmenorrhea willing to reserve the uterus and a poor response to medical
      management. Gynecologic examination revealed that the uteri sizes were 9 to 14
      weeks. Transvaginal ultrasonography revealed that the lesions were 4 to 7 cm in
      size. INTERVENTIONS: Laparoscopic resection of the diffuse adenomyosis lesion was
      conducted after temporary blocking of the uterine artery with a rubber belt.
      MEASUREMENTS AND MAIN RESULTS: The traditional methods for injecting diluted
      vasopressin in the myometrium around the affected area and a half-life period of
      30 minutes were used. Many adenomyosis patients with severe dysmenorrhea and
      menometrorrhagia have a large lesion; thus, the operating time is longer. The
      maximum dose of vasopressin is 20 units daily, and hypertensive patients have a
      contraindication. We made an incision of the broad ligament of the avascular area
      near the uterine artery and pulled the rubber pressure pulse ligation tightly
      through to temporarily block the uterine artery without vasopressin completely
      through the laparoscopic resection of the diffuse adenomyosis lesion.
      Intraoperative blood loss was only 120 to 230 mL. In this video, we show a
      simpler technique for temporarily blocking the uterine artery in laparoscopic
      resection of diffuse adenomyosis with a stepwise expiation. A levonorgestrel
      releasing intrauterine system (Mirena; Bayer, Leverkusen, Germany) was placed in
      the uterus from the vagina immediately after surgery. At the 3-25 month (10.67+/
      12.42) follow-up, visual analog scale scores were obviously reduced, and the
      menstrual quantity and amenorrhea dramatically declined after the surgery. All
      patients had no recurrence and no Mirena loss as assessed by vaginal ultrasound
      and the visual analog scale [1]. Estrogen was maintained at the normal level
      after 3 months. This study was approved by the Institutional Review Board of the
      Changzhou Maternal and Child Health Hospital Affiliated to Nanjing Medical
      University. CONCLUSION: The incidence of adenomyosis is a newer trend that is
      being used in patients with a poor response to medical management of uterine
      lesions and large lesions in China. Using the rubber belt to temporarily block
      the uterine artery in laparoscopic resection of the diffuse adenomyosis lesion
      offers the possibility of the rubber belt being effective, safe, and
      reproducible. Minimally invasive surgery in expert hands is the preferred
      solution of an increasing number of patients after drug treatment failure.

PMID- 27702703
TI  - Adnexal Torsion in Postmenopausal Women: Clinical Presentation and Risk of
      Ovarian Malignancy.
AB  - STUDY OBJECTIVE: To investigate the clinical presentation, operative outcome, and
      incidence of malignancy in postmenopausal women who were diagnosed with adnexal
      torsion. DESIGN: Retrospective cohort study (Canadian Task Force classification
      II-2). SETTING: Tertiary university-affiliated hospital. PATIENTS: Postmenopausal
      women diagnosed with adnexal torsion between 1995 and 2014 (study group) were
      reviewed and compared with 220 premenopausal patients diagnosed with adnexal
      torsion during the same time period. INTERVENTION: Demographic data, clinical
      signs and symptoms, and intra- and postoperative characteristics were compared
      between the 2 groups. MEASUREMENTS AND MAIN RESULTS: During the study period 44
      postmenopausal women were diagnosed with adnexal torsion. Continuous dull pain
      was the most common presenting symptom in the postmenopausal group (57%), whereas
      acute-onset sharp pain was the predominant symptom in the premenopausal group
      (86%). The time interval from admission to surgery was significantly longer in
      the postmenopausal group (24 vs 6 hours, p < .001). Laparoscopic surgery was
      performed in 84.5% of the cases in the premenopausal group, whereas it was
      carried out in only 50% of cases in the postmenopausal group (p < .001). Four
      women in the postmenopausal group were diagnosed with malignancy, whereas only 1
      case of malignancy was found in the premenopausal group (9% vs .4%, respectively;
      p = .003). CONCLUSIONS: Adnexal torsion in postmenopausal women is an uncommon
      event with a unique presentation. Because ovarian malignancy is not an uncommon
      finding in this group of patients, preparation for more extensive surgery should
      be contemplated.

PMID- 27702704
TI  - Minimally Invasive Surgical Staging for Ovarian Carcinoma: A Propensity-Matched
      Comparison With Traditional Open Surgery.
AB  - STUDY OBJECTIVE: Growing evidence supports the safety of a laparoscopic approach
      for patients affected by apparent early-stage ovarian cancer. However, no well
      designed studies comparing laparoscopic and open surgical staging are available.
      In the present investigation we aimed to provide a balanced long-term comparison
      between these 2 approaches. DESIGN: Retrospective study (Canadian Task Force
      classification II-2). SETTING: Tertiary center. PATIENTS: Data of consecutive
      patients affected by early-stage ovarian cancer who had laparoscopic staging were
      matched 1:1 with a cohort of patients undergoing open surgical staging. The
      matching was conducted by a propensity-score comparison. INTERVENTION:
      Laparoscopic and open surgical staging. MEASUREMENTS AND MAIN RESULTS: Fifty
      patient pairs (100 patients: 50 undergoing laparoscopic staging vs 50 undergoing
      open surgical staging) were included. Demographic and baseline oncologic
      characteristics were balanced between groups (p > .2). We observed that patients
      undergoing laparoscopic staging experienced longer operative time (207.2 [71.6]
      minutes vs 180.7 [47.0] minutes; p = .04), lower blood loss (150 [52.7] mL vs
      339.8 [225.9] mL; p < .001), and shorter length of hospital stay (4.0 [2.6] days
      vs 6.1 [1.6] days; p < .001) compared with patients undergoing open surgical
      staging. No conversion to open surgery occurred. Complication rate was similar
      between groups. No difference in survival outcomes were observed, after a mean
      (SD) follow-up of 49.5 (64) and 52.6 (31.7) months after laparoscopic and open
      surgical staging, respectively. CONCLUSIONS: Our findings suggest that the
      implementation of minimally invasive staging does not influence survival outcomes
      of patients affected by early-stage ovarian cancer. Laparoscopic staging improved
      patient outcomes, reducing length of hospital stay. Further large prospective
      studies are warranted.

PMID- 27702705
TI  - Robotic-assisted Reconstruction of the Cervix and Vagina by Small Intestinal
      Submucosa Graft and Fusion of the Hemiuterus.
AB  - STUDY OBJECTIVE: To describe our technique of robotic-assisted reconstruction of
      the cervix and vagina using a small intestinal submucosa (SIS) graft and fusion
      of the hemiuterus. DESIGN: A step-by-step explanation of the procedure using
      video. SETTING: Congenital complete vaginal and cervical atresia is rare. Some
      patients have urinary system abnormality. No standardized surgical treatment
      guideline was available, and the performance varies for each patient.
      INTERVENTIONS: We performed a robotic-assisted reconstruction of the cervix and
      vagina using an SIS graft (Cook Medical, Bloomington, IN) and fusion of the
      hemiuterus for a 12-year-old girl from China diagnosed with congenital vaginal
      and cervical atresia (U4C4V4). She complained of severe abdominal periodic pain
      for 2 months. Mammary development and her serum sex hormone were within normal
      range. The patient has a single kidney. The diagnosis was made according to
      clinical characteristics, physical examination, and magnetic resonance imaging
      and classified using the European Society of Human Reproduction and Embryology
      /European Society for Gynaecological Endoscopy (ESHRE/ESGE) system. There was a
      hematometra of 7-cm diameter in her pelvis. We constructed a novel vagina by
      sharp and blunt separation and connected it to the uterine cavity. With the SIS
      graft, we reconstructed her cervix and vagina, and we fused the hemiuterus to
      make the uterine cavity spacious. The operating time was 260 minutes, and blood
      loss was 300 mL. She recovered well after the operation without any
      complications. After surgery, the patient has had normal menstruation without
      pain. She insists on wearing the vaginal mold 24 hours per day. The follow-up was
      10 months. The length of the vagina was 9 cm and the width was 3 cm. CONCLUSION:
      Robotic-assisted reconstruction of the cervix and vagina using an SIS graft and
      fusion of the hemiuterus is feasible and safety. However, additional studies are
      required.

PMID- 27702706
TI  - Radiosurgery for Secondary Trigeminal Neuralgia: Revisiting the Treatment
      Paradigm.
AB  - BACKGROUND: The mechanisms by which surgery and radiation elicit pain relief in
      trigeminal neuralgia (TN) secondary to mass lesions vary widely. We aimed to
      evaluate the outcomes of radiation to the nerve rather than to the lesion in the
      treatment of secondary TN. METHODS: We retrospectively reviewed all patients who
      underwent radiation at the University of California, Los Angeles for TN secondary
      to tumors. The Barrow Neurological Institute (BNI) pain score was used to
      evaluate pain outcomes. RESULTS: Twelve patients were identified; 4 were male and
      8 were female. Their mean age at treatment was 59.8 years (range, 47.7-84.7
      years). Tumor pathologies included meningioma (n = 8), squamous cell carcinoma (n
      = 2), vestibular schwannoma (n = 1), and hemangiopericytoma (n = 1). No patient
      suffered from multiple sclerosis. Ten patients underwent initial radiation
      targeting their tumors-radiosurgery in 3 and fractionated radiation therapy in 7
      others. Only 6 among these 10 experienced at least partial relief, which lasted a
      mean 6 months. Radiosurgery targeting the trigeminal nerve was eventually
      performed. Overall, 10 of 12 (83.3%) patients experienced good initial pain
      relief, complete in 6 (50%) patients. Pain recurred in 6 (60%) patients, at a
      mean 41 months after radiosurgery to the trigeminal nerve. Three patients
      experienced facial sensory dysfunction postprocedurally at a mean follow-up
      duration of 57 months. CONCLUSION: In contrast to tumor radiation, radiosurgery
      to the trigeminal nerve root resulted in reasonable and longer pain reduction, on
      par with the literature regarding surgical resection, with low risk of additional
      complications.

PMID- 27702707
TI  - Bilateral Chronic Subdural Hematoma Treated by YL-1 Type Hematoma Aspiration
      Needle Complicated by Hemorrhage of the Basal Ganglia and Brainstem.
AB  - BACKGROUND: A 72-year-old man with bilateral chronic subdural hematomas was
      admitted to our department and treated using a YL-1 type hematoma aspiration
      needle. The treatment was complicated by hemorrhage of the basal ganglia and
      brainstem. This patient had no history of hypertension. We evaluated the relevant
      literature to analyze the causes of cerebral hemorrhage in similar patients.
      CONCLUSIONS: This case report illustrates that the stability of the intracranial
      pressure should be closely monitored during the surgical treatment of chronic
      subdural hematomas, and large fluctuations in the cerebral perfusion pressure
      should be avoided during the operation. We also propose improvements in the
      technical details of the operative treatment of chronic subdural hematomas.

PMID- 27702708
TI  - Neurophysiology of myoclonus and progressive myoclonus epilepsies.
AB  - The high temporal resolution of neurophysiological recordings makes them
      particularly suited to faithfully describing the time course of rapid events such
      as myoclonus and to precisely measure its time relationship with other related
      activities. In progressive myoclonus epilepsies (PMEs) polygraphy with
      simultaneous EMG-EEG recordings is a crucial tool for defining the characteristic
      of myoclonic jerks their topography over different muscles (namely antagonists),
      their time course and relationship with vigilance muscle activation and
      stimulations. Moreover on polygraphic recordings it is possible to detect EEG
      activities associated to myoclonic jerks and define their time relationship with
      myoclonus thus differentiating cortical types of myoclonus from subcorticallly
      generated ones. Tanks to the back averaging technique non obvious time-locked EEG
      potentials can be detected on polygraphy , furthermore in stimulus sensitive
      myoclonus the analysis can include the potential evoked by the somatosensory
      stimulus (SEP). The polygraphic recording also gives information on muscle
      activity suppression occurring after jerk or as pure negative myoclonus. Besides
      the time domain analysis, techniques based on frequency analysis have been
      developed to evaluate EEG-EMG coherence. The neurophysiological techniques
      provide investigators and clinicians with an invaluable information to define the
      type of myoclonus and its generating circuitry thus substantially contributing in
      the diagnosis and management of PMEs.

PMID- 27702710
TI  - Fructans in the first 1000 days of life and beyond, and for pregnancy.
AB  - Inulin-based prebiotics are non-digestible polysaccharides that influence the
      composition of the gut microbiota in infants and children, notably eliciting a
      bifidogenic effect with high short chain fatty acid levels. Inulin, a generic
      term that comprises beta-(2,1)-linked linear fructans, is typically isolated from
      the chicory plant root, and derivatives such as oligofructose and long chain
      inulin appear to have different physiological properties. The first 1000 days of
      a child's life are increasingly recognized as a critical timeframe for health
      also into adulthood, whereby nutrition plays a key role. There is an ever
      increasing association between nutrition and gut microbiota composition and
      development, with life health status of an individual. This review summarizes the
      latest knowledge in the infant gut microbiota from preterms to healthy newborns,
      as well as in malnourished children in developing countries. The impact of inulin
      or mixtures thereof on infants, toddlers and young children with respect to
      intestinal function and immunity in general, is reviewed. Possible benefits of
      prebiotics to support the gut microbiome of malnourished infants and children,
      especially those with infections in the developing world, are considered, as well
      as for the pregnant mothers health. Importantly, novel insights in metabolic
      programming are covered, which are being increasing recognized for remarkable
      impact on long term offspring health, and eventual potential beneficial role of
      prebiotic inulins. Overall increasing findings prompt the potential for gut
      microbiota-based therapy to support health or prevent the development of certain
      diseases from conception to adulthood where inulin prebiotics may play a role.

PMID- 27702709
TI  - Lafora disease.
AB  - Lafora disease (LD) is an autosomal recessive progressive myoclonus epilepsy due
      to mutations in the EPM2A (laforin) and EPM2B (malin) genes, with no substantial
      genotype-phenotype differences between the two. Founder effects and recurrent
      mutations are common, and mostly isolated to specific ethnic groups and/or
      geographical locations. Pathologically, LD is characterized by distinctive
      polyglucosans, which are formations of abnormal glycogen. Polyglucosans, or
      Lafora bodies (LB) are typically found in the brain, periportal hepatocytes of
      the liver, skeletal and cardiac myocytes, and in the eccrine duct and apocrine
      myoepithelial cells of sweat glands. Mouse models of the disease and other
      naturally occurring animal models have similar pathology and phenotype.
      Hypotheses of LB formation remain controversial, with compelling evidence and
      caveats for each hypothesis. However, it is clear that the laforin and malin
      functions regulating glycogen structure are key. With the exception of a few
      missense mutations LD is clinically homogeneous, with onset in adolescence.
      Symptoms begin with seizures, and neurological decline follows soon after. The
      disease course is progressive and fatal, with death occurring within 10 years of
      onset. Antiepileptic drugs are mostly non-effective, with none having a major
      influence on the progression of cognitive and behavioral symptoms. Diagnosis and
      genetic counseling are important aspects of LD, and social support is essential
      in disease management. Future therapeutics for LD will revolve around the
      pathogenesics of the disease. Currently, efforts at identifying compounds or
      approaches to reduce brain glycogen synthesis appear to be highly promising.

PMID- 27702711
TI  - Optimal nutrition therapy in paediatric critical care in the Asia-Pacific and
      Middle East: a consensus.
AB  - BACKGROUND AND OBJECTIVES: Current practices and available resources for
      nutrition therapy in paediatric intensive care units (PICUs) in the Asia Pacific
      Middle East region are expected to differ from western countries. Existing
      guidelines for nutrition management in critically ill children may not be
      directly applicable in this region. This paper outlines consensus statements
      developed by the Asia Pacific-Middle East Consensus Working Group on Nutrition
      Therapy in the Paediatric Critical Care Environment. Challenges and
      recommendations unique to the region are described. METHODS AND STUDY DESIGN:
      Following a systematic literature search from 2004-2014, consensus statements
      were developed for key areas of nutrient delivery in the PICU. This review
      focused on evidence applicable to the Asia Pacific-Middle East region. Quality of
      evidence and strength of recommendations were rated according to the Grading of
      Recommendation Assessment, Development and Evaluation approach. RESULTS: Enteral
      nutrition (EN) is the preferred mode of nutritional support. Feeding algorithms
      that optimize EN should be encouraged and must include: assessment and monitoring
      of nutritional status, selection of feeding route, time to initiate and advance
      EN, management strategies for EN intolerance and indications for using parenteral
      nutrition (PN). Despite heterogeneity in nutritional status of patients,
      availability of resources and diversity of cultures, PICUs in the region should
      consider involvement of dieticians and/or nutritional support teams. CONCLUSIONS:
      Robust evidence for several aspects of optimal nutrition therapy in PICUs is
      lacking. Nutritional assessment must be implemented to document prevalence and
      impact of malnutrition. Nutritional support must be given greater priority in
      PICUs, with particular emphasis in optimizing EN delivery.

PMID- 27702712
TI  - Melamine-contaminated milk formula and its impact on children.
AB  - The melamine contaminated milk powder contamination scandal occurred in China in
      2008. Its main consequences so far have been urinary stone formation in children
      with associated renal damage and increased child mortality. Eight years have
      passed, but food safety issues still remain of concern in the daily lives of
      millions of Chinese. Vigilance is required to ensure no recurrence of such food
      safety problems. Ongoing studies focus on the early detection of food industry
      malpractice, mechanisms whereby these toxic substances induce disease and how its
      advent may be prevented and better managed. Melamine undergoes renal excretion,
      but is metabolized slowly and excreted largely unchanged in the urine. Urinary
      melamine measurement may provide a rapid and inexpensive way to identify exposure
      to melamine adulterated food items. Although most patients with melaminerelated
      urinary stones (MUS) have been responsive to conservative treatment, longer time
      follow-up is needed to assess chronic effects. Aside from MUS, melamine is a
      recognized carcinogen and can induce urinary tract tumours. Very little is known
      about the effects of excessive exposure to melamine contaminated milk powder in
      infants on growth, adolescent and adult health, although short-term effects have
      become apparent during the scandal.

PMID- 27702713
TI  - Future food.
AB  - Food systems have changed markedly with human settlement and agriculture,
      industrialisation, trade, migration and now the digital age. Throughout these
      transitions, there has been a progressive population explosion and net ecosystem
      loss and degradation. Climate change now gathers pace, exacerbated by ecological
      dysfunction. Our health status has been challenged by a developing people
      environment mismatch. We have regarded ecological conquest and innovative
      technology as solutions, but have not understood how ecologically dependent and
      integrated we are. We are ecological creatures interfaced by our sensoriness,
      microbiomes, shared regulatory (endocrine) mechanisms, immune system, biorhythms
      and nutritional pathways. Many of us are 'nature-deprived'. We now suffer what
      might be termed ecological health disorders (EHD). If there were less of us,
      nature's resilience might cope, but more than 9 billion people by 2050 is
      probably an intolerable demand on the planet. Future food must increasingly take
      into account the pressures on ecosystem-dependent food systems, with foods
      probably less biodiverse, although eating in this way allows optimal health;
      energy dysequilibrium with less physical activity and foods inappropriately
      energy dense; and less socially-conducive food habits. 'Personalised Nutrition',
      with extensive and resource-demanding nutrigenomic, metabolomic and microbiomic
      data may provide partial health solutions in clinical settings, but not be
      justified for ethical, risk management or sustainability reasons in public
      health. The globally prevalent multidimensional malnutritional problems of food
      insecurity, quality and equity require local, regional and global action to
      prevent further ecosystem degradation as well as to educate, provide sustainable
      livelihoods and encourage respectful social discourse and practice about the role
      of food.

PMID- 27702714
TI  - Children with atopic dermatitis in Daejeon, Korea: individualized nutrition
      intervention for disease severity and nutritional status.
AB  - BACKGROUND AND OBJECTIVES: Atopic dermatitis is one of the most common pediatric
      chronic inflammatory skin diseases, and certain food allergens and nutrients are
      closely related to the development and severity of atopic dermatitis. While
      avoidance of the causative foods is considered the mainstay of treatment,
      unverified excessive restriction might induce unnecessary limitations in the food
      intake, consequently leading to nutritional deficiencies and poor growth. This
      study aimed to identify the characteristics and nutrient intake status in
      children with atopic dermatitis and to investigate the effects of individualized
      nutrition intervention. METHODS AND STUDY DESIGN: We retrospectively reviewed
      electronic medical records of 77 pediatric patients with atopic dermatitis who
      received 4 months of individualized nutrition intervention combined with an
      elimination diet. The patient characteristics, nutrient intake status, and
      clinical status were examined before and after the intervention. RESULTS: Before
      the intervention, 5 children had a weight for height z-score below -2.0, and
      48.1% had experienced food restriction; these children showed a significantly
      higher SCORing of Atopic Dermatitis index than those without experiences, with
      the number of restricted foods before the intervention positively correlating
      with the disease severity. The intakes of n-6 and n-3 fatty acids, calcium,
      folate, and vitamin D were lower than the recommended nutrient intakes for
      Koreans. After the intervention, the weight for height z-score of 35 children was
      significantly increased and their SCORing of Atopic Dermatitis index was
      significantly reduced (p<0.05). CONCLUSIONS: Individualized nutrition
      intervention appears useful for alleviating the severity of atopic dermatitis and
      improving the growth status by improving the nutrient intake.

PMID- 27702716
TI  - Enteral nutrition preference in critical care: fibre-enriched or fibre-free?
AB  - BACKGROUND AND OBJECTIVES: This study's main aim was to observe the effects of a
      fibre-enriched nutrition solution on requisite feeding volume, which is directly
      proportional to energy intake in mechanically ventilated patients with enteral
      nutrition. METHODS AND STUDY DESIGN: Some 120 patients who required mechanical
      ventilation and enteral nutrition with a nasogastric tube were studied. Upon ICU
      admission, the patient's age, gender, weight, height, comorbidities, diagnosis
      and APACHE II score were recorded. We assigned two diets to the patients
      randomly. The control group received the fibre-free nutrition solution. The study
      group, received the fibreenriched nutrition solution. Prescribed feeding volume
      and administered feeding volume, gastric residual volume (GRV), volume ratio
      (VR), diarrhoea score and gastrointestinal complications (GIC) were recorded,
      along with daily biochemistry. RESULTS: The two groups did not differ with
      respect to age, sex, weight, BMI, APACHE II score, target caloric intake or GRV
      (p>0.05). On days four and five, the study group had higher VR values (p<0.05).
      Seventy-one (59%) patients had at least one gastrointestinal complication; 44
      (73%) of them were controls and 27 (45%) of them study patients. The most
      commonly observed GIC was diarrhoea. Thirty-eight patients had diarrhoea in
      control group, and twenty-two patients had diarrhoea in study group, and this
      difference was statistically significant (p<0.001). There were no significant
      differences between the groups about vomiting and regurgitation. CONCLUSIONS: We
      suggest that ICU staff initiate enteral nutrition with fibre-enriched formulas
      rather than fibre-free formulas to avoid frequent feeding interruptions that
      cause protein energy malnutrition in ICU patients.

PMID- 27702715
TI  - Simultaneous coffee caffeine intake and sleep deprivation alter glucose
      homeostasis in Iranian men: a randomized crossover trial.
AB  - BACKGROUND AND OBJECTIVES: Sleep deprivation and coffee caffeine consumption have
      been shown to affect glucose homeostasis separately, but the combined effects of
      these two variables are unknown. METHODS AND STUDY DESIGN: Forty-two healthy
      Iranian men, aged 20-40 years old, were assigned to three groups in a randomised
      crossover trial involving three treatments with two-week washout periods.
      Subjects were moderate coffee consumers (<=3 cups/day), and had a Pittsburgh
      Sleep Quality Index <=5. Each treatment involved three nights of deprived sleep
      (4 hrs. in bed) plus 3*150 cc/cup of boiled water (BW treatment), decaffeinated
      coffee (DC treatment, without sugar, 99.9% caffeine-free), and caffeinated coffee
      (CC treatment, without sugar, 65 mg caffeine/ cup). DC and CC treatments were
      blinded. At the end of each treatment, fasting serum glucose (using enzyme
      assays) and insulin (using electrochemiluminescence immunoassay) were measured
      and, again, two hours after an oral glucose tolerance test (OGTT). Insulin
      resistance was quantified with the homeostasis model. RESULTS: Repeated measures
      ANOVA indicated no significant difference between the treatments in fasting serum
      glucose (p=0.248) or insulin resistance (p=0.079). However, ANOVA demonstrated
      differences between treatments in fasting serum insulin (p=0.004) and glucose, as
      well as insulin after OGTT (p<0.001). Pairwise comparisons test (within subjects)
      showed that the CC treatment yielded higher serum glucose and insulin after OGTT
      (p<0.001), higher fasting serum insulin (p=0.001), and increased insulin
      resistance (p=0.039) as compared to the DC treatment. CONCLUSIONS: Thus
      caffeinated coffee was more adverse for glucose homeostasis compared to
      decaffeinated coffee in individuals who were simultaneously sleep deprived.

PMID- 27702717
TI  - Combined chromium and magnesium decreases insulin resistance more effectively
      than either alone.
AB  - BACKGROUND AND OBJECTIVES: Peroral supplementation with trivalent-chromium (Cr)
      or magnesium (Mg) has been shown to improve insulin resistance (IR). The
      objective of this study was to determine whether combined peroral supplementation
      with Cr and Mg improves IR more effectively than Cr or Mg alone. METHODS AND
      STUDY DESIGN: Subjects (n=120, age range 45-59 years old) and diagnosed with IR
      were randomly divided into four groups and monitored for a period of 3 months:
      group 1 (the placebo control group), group 2 (160 MUg/d Cr), group 3 (200 mg/d
      Mg), and group 4 (160 MUg/d Cr plus 200 mg/d Mg). Fasting blood glucose (FBG),
      fasting insulin (FIns), erythrocyte Cr and Mg content, and glucose-transporter-4
      (GLUT4) and glycogen-synthase-kinase-3beta (GSK3beta) mRNA levels in activated T
      lymphocytes were measured, and insulin resistant index (IRI) was calculated.
      RESULTS: Significant decreases between the baseline and study conclusion values
      of FBG (0.37 mmol/L, p<0.01), FIns (2.91 MUIU/mL, p<0.01) and IRI (0.60, p<0.01)
      were observed in group 4, but not groups 1-3. Similarly, compared with baseline,
      significant changes in GLUT4 (2.9-fold increase, p<0.05) and GSK3beta (2.2-fold
      decrease, p<0.05) mRNA levels in activated T-lymphocyte were observed at the
      study's conclusion in group 4, but not in groups 1-3. CONCLUSIONS: Our results
      indicate that combining peroral supplementation with Cr and Mg improves IR more
      effectively than Cr or Mg alone, and this may be attributable to increased
      induction and repression, respectively, of GLUT4 and GSK3beta expression.

PMID- 27702718
TI  - 25 hydroxy vitamin D is higher when a renal multivitamin is given with
      cholecalciferol at hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Seventy six hemodialysis (HD) patients were used in a
      prospective randomized and clinical trial to determine if a multivitamin with
      vitamin D (cholecalciferol 12,000 IU/week) given during dialysis would improve
      the vitamin D status of hemodialysis subjects. METHODS AND STUDY DESIGN: Subjects
      were randomly assigned to two groups: 37 subjects were in the renal multivitamin
      without vitamin D (MV) group and 39 subjects were in a multivitamin route with
      vitamin D (MVD) group (12,000 IU of cholecalciferol per week). All subjects were
      given 2 multivitamin tablets at their 3 HD sessions each week for 20 weeks. Serum
      25(OH)D, calcium (Ca), and phosphorus (P) levels were evaluated. RESULTS: At
      baseline, mean serum 25(OH)D were below adequate (<30 ng/mL) in the MV group
      (23.5+/-12.2 ng/mL) and in the MVD group (20.8+/-10.3 ng/mL). A significant
      increase was seen in serum 25(OH)D levels (37.7+/-11.4 ng/mL; p<0.001) in the MVD
      group after vitamin D supplementation with no rise in the MV group value (21.7+/
      11.4 ng/mL; p=0.06). Prior to supplementation, 17.9% of patients in the MVD group
      had adequate serum 25(OH)D level and post supplementation 76.9% in the MVD group
      had adequate serum 25(OH)D. In the MV group, 18.9% subjects had adequate serum
      25(OH)D levels at baseline with 18.9% having 25(OH)D >30 ng/mL at the end of the
      study. There were no significant differences in group values for serum Ca and P.
      CONCLUSION: The majority of HD subjects given a multivitamin with cholecalciferol
      at dialysis had improvement in their vitamin D status.

PMID- 27702719
TI  - Cod skin peptide reduces chemotherapy-induced toxicity in gastric cancer
      patients.
AB  - BACKGROUND AND OBJECTIVES: The present study was conducted to evaluate the effect
      of cod skin peptide (CSPE) on chemotherapy-induced toxicity in gastric cancer
      patients. METHODS AND STUDY DESIGN: A cohort of 60 gastric cancer patients for
      chemotherapy was randomly divided into two groups (n=30 per group), who were
      orally treated with either supplemental CSPE or placebo apart from chemotherapy.
      The hematologic and gastrointestinal toxicities experienced by the patients, as
      well as their Karnofsky Performance Status (KPS) as an index of quality of life
      was evaluated. RESULTS: Leukocyte counts and haemoglobin levels were
      significantly reduced in the group treated with peptide (p<0.05), while
      gastrointestinal toxicity was not affected (p>0.05). KPS consists of 11
      categories of quality of life, and the score denoted in deciles ranges from 100
      (asymptomatic, normal function) to 0 (death). The KPS score is used to evaluate a
      cancer patient's ability to function at work and home, the severity of symptoms,
      and the patient's need for personal and medical care. Treatment with CSPE
      significantly improved the quality of life of patients, as indicated by increased
      KPS scores (p<0.05). CONCLUSIONS: CSPE can potentially be considered as a food
      supplement that can be used to improve the quality of life of cancer patients.

PMID- 27702720
TI  - Coffee consumption is associated with lower serum aminotransferases in the
      general Korean population and in those at high risk for hepatic disease.
AB  - BACKGROUND AND OBJECTIVES: The favourable effects of coffee on liver enzymes have
      been reported worldwide. This study investigated the association between coffee
      consumption and serum aminotransferase concentration in Korean adults. METHODS
      AND STUDY DESIGN: Data were obtained from the fourth and fifth Korea National
      Health and Nutrition Examination Surveys. Elevated alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST) concentration were defined as >30 IU/L for
      men and >19 IU/L for women. The risk of elevated ALT and AST according to general
      characteristics and frequency of coffee consumption were tested by chi-square
      tests and multiple logistic regression analyses. RESULTS: The prevalence of
      elevated ALT was 27.4%, 27.8%, and 26.9% in subjects who drank <1, 1, and >=2
      times/day, respectively. The proportions of individuals with elevated AST were
      32.5%, 33.1%, and 26.7% in subjects who drank <1, 1, and >=2 times/day,
      respectively. The aORs for elevated ALT and AST were significantly lower in
      subjects who drank >=2 times of coffee/day than in those who drank <1 time/day
      (ALT: aOR=0.86, 95% CI=0.79-0.94; AST: aOR=0.83, 95% CI=0.76-0.91). In subgroup
      analysis, consumption of >=2 times/day was associated with lower ORs for elevated
      ALT in the high-risk group overall and in the viral hepatitis and obesity
      subgroups, respectively. In sensitivity analysis, reduced frequency of coffee
      consumption was associated with an increased risk for elevated liver enzymes,
      although an association between coffee consumption and elevated ALT was not
      observed in women or current smokers. CONCLUSIONS: Higher coffee consumption was
      associated with lower risk of elevated aminotransferase concentration in Korean
      adults.

PMID- 27702721
TI  - Habitual dietary calcium intakes and calcium metabolism in healthy adults
      Chinese: a systematic review and meta-analysis.
AB  - To investigate the metabolic differences of calcium requirements between Chinese
      and Westerners, we examined systematically the characteristics of calcium
      metabolism in Chinese adults with habitual dietary calcium intakes. We searched
      PubMed, Cochrane Library, SinoMed, and National Index to Chinese Newspapers &
      Periodicals, from inception to March 17, 2015, as well as the bibliographies of
      any relevant papers and journals, for trials assessing calcium metabolism in
      healthy Chinese adults within 18-60 years of age on the typical Chinese diet. We
      extracted a standardized dataset from metabolic studies that reported intake,
      retention, urinary excretion, faecal excretion and/or fractional absorption of
      calcium. We pooled data with a random effects meta-analysis. Of 2,046 citations
      identified by the search strategy, 12 studies (comprising 137 participants, 13
      aggregate data deriving from 257 individual data) met the inclusion criteria.
      Metabolic data with self-chosen or typical Chinese diets were analyzed. Mean
      daily intakes of calcium ranged between 288 and 948 mg. Mean calcium retentions
      of each study were between 13 and 294 mg/d. The overall pooled value for dietary
      intake, urinary excretion, faecal excretion, retention and fractional absorption
      of calcium were 583 mg/d, 117 mg/d, 381 mg/d, 72 mg/d and 33.3%. Dietary calcium
      intake and faecal calcium excretion explained almost 85% of the heterogeneity of
      calcium retention. Chinese adults could maintain a positive calcium balance with
      plant-based diets at calcium intakes as low as 300 mg/d through increasing
      fractional calcium absorption and decreasing calcium excretion in urine and
      faeces.

PMID- 27702722
TI  - Population-based association between urinary excretion of sodium, potassium and
      its ratio with albuminuria in Chinese.
AB  - BACKGROUND AND OBJECTIVES: Albuminuria is a risk factor for cardiovascular and
      renal disease. However, little is known about the association of 24 h urinary
      sodium and potassium excretion with albuminuria in China. The aim of this study
      was to examine this association by analyzing the data from 1,975 Chinese adults
      living in north China. METHODS AND STUDY DESIGN: Excretion of urinary sodium,
      potassium and albumin was assessed in a single 24-h urine sample for each
      participant. Height, weight, waist circumference and blood pressure were measured
      and body mass index was determined as weight divided by square height. Fasting
      blood sample was collected and fasting glucose was measured. RESULTS: The average
      24-h urinary sodium and potassium excretion were 232 mmol and 40.8 mmol,
      resulting a mean sodium to potassium ratio of 6.7. The median (Q1-Q3) 24-h
      urinary albuminuria excretion was 6.1 mg (4.5-8.7 mg). Overall, urinary sodium
      excretion was positively associated with albumin excretion (beta=0.029, p<0.001).
      This association was independent of major cardiovascular risk factors including
      age, gender, systolic blood pressure, body mass index, fasting glucose, waist
      circumference, hypertensive drug treatment, and smoking. Moreover, the relation
      of sodium and albumin was similar in the subgroups stratified by gender,
      adiposity and diabetic status. No significant associations of potassium excretion
      or sodium to potassium ratio with urinary albumin excretion were observed.
      CONCLUSIONS: In cross-sectional analyses, high sodium intake was shown to be
      associated with increased urinary albuminuria in the general Chinese adult
      population, supporting salt restriction for renal and cardiovascular health
      benefit.

PMID- 27702723
TI  - Truncal and leg fat associations with metabolic risk factors among Chinese
      adults.
AB  - BACKGROUND AND OBJECTIVES: To examine the associations of regional body fat
      distribution with metabolic risk factors among Chinese. METHODS AND STUDY DESIGN:
      Truncal fat (TF) and leg fat (LF) were measured by dualenergy X-ray
      absorptiometry (DXA) among 947 adults, and abdominal visceral fat (VAT) and
      subcutaneous fat (SAT), upper leg SAT were measured by magnetic resonance image
      (MRI) among 103 adults during 2008-2013. Metabolic risk factors included fasting
      blood glucose, total triglyceride, total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, and metabolic syndrome (MetS).
      RESULTS: TF showed adverse effect while LF showed beneficial effect on metabolic
      risk factors, and all these effects were independent of body mass index (BMI)
      (mostly p<0.01). Individuals with higher TF and lower LF experienced the highest
      risk of MetS compared to other subgroups of combination of TF and LF (all
      p<0.05). Abdominal VAT was positively associated with risk of MetS (men: odds
      ratio (OR)=4.45, 95% confidence interval (CI): 1.18, 16.8; women: OR=6.54, 95%
      CI: 1.08, 39.6) and serum triglyceride (men: beta (beta)=0.379, 95% CI: 0.090,
      0.667; women: beta=0.700, 95% CI: 0.327, 1.07). Upper leg SAT showed an opposite
      association with most metabolic factors compared to abdominal SAT and VAT,
      however, the association was not statistically significant. CONCLUSION: TF and LF
      showed opposite effects on metabolic risk factors among Chinese adults. Abdominal
      VAT, but not abdominal SAT, was positively associated with serum triglyceride and
      risk of MetS. Future studies are warranted to examine the potential mechanism of
      the opposite effects between TF and LF on metabolic risk factors among Chinese.

PMID- 27702724
TI  - Pre-pregnancy body mass index and gestational weight gain in Thai pregnant women
      as risks for low birth weight and macrosomia.
AB  - BACKGROUND AND OBJECTIVES: Maternal pre-pregnancy body mass index (BMI) and
      gestational weight gain (GWG) have been reported to be associated with pregnancy
      outcomes. Due to the nutrition transition in Thailand, the double burden of
      malnutrition is increasing and this may have negative consequences on birth
      outcomes. This study aimed to investigate the relationship between pre-pregnancy
      BMI and GWG with the risks of low birth weight and macrosomia. METHODS AND STUDY
      DESIGN: We performed a secondary analysis of data obtained from an iodine
      supplementation trial in mildly iodine-deficient Thai pregnant women. Pre
      pregnancy BMI was classified using the WHO classification. GWG was categorized
      using the IOM recommendation. Binary and multinomial logistic regressions were
      performed. RESULTS: Among 378 pregnant women, the prevalence of pre-pregnancy
      underweight (BMI<18.5 kg/m2) and overweight (BMI>=25 kg/m2) were 17.2% and 14.3%,
      respectively. Normal weight women had the highest median GWG [15.0 (12.0, 19.0)
      kg] when compared to overweight women [13.2 (9.0, 16.3) kg]. Forty-one percent of
      women had excessive GWG, while 23% of women gained weight inadequately. Women
      with a high pre-pregnancy BMI had a 7-fold higher risk of having a macrosomic
      infant. Women who had excessive GWG were 8 times more likely to deliver a newborn
      with macrosomia. CONCLUSIONS: Both high pre-pregnancy maternal weight and
      excessive weight gain during pregnancy increase risk of infant macrosomia.
      Therefore, maintaining normal body weight before and throughout pregnancy should
      be recommended in order to reduce the risk of excessive infant birth weight and
      its associated complications.

PMID- 27702725
TI  - An on-line database for human milk composition in China.
AB  - BACKGROUND AND OBJECTIVES: Understanding human milk composition is critical for
      setting nutrient recommended intakes (RNIs) for both infants and lactating women.
      However, nationwide human milk composition remains unavailable in China. METHODS
      AND STUDY DESIGN: Through cross-sectional study, human milk samples from 11
      provinces in China were collected and their compositions were analyzed.
      Nutritional and health status of the lactating women and their infants were
      evaluated through questionnaire, physical examination and biochemical indicators.
      RESULTS: A total of 6,481 breast milk samples including colostrum (1,859),
      transitional milk (1,235) and mature milk (3,387) were collected. Contents of
      protein, fat, lactose, total solid and energy of more than 4,500 samples were
      analyzed using a human milk analyzer. About 2,000 samples were randomly selected
      for 24 mineral analyses. Free B-vitamins including thiamin, riboflavin,
      pyridoxal, pyridomine, pyridoxamine, nicotinamide, nicotinic acid, flavin adenine
      dinucleotide (FAD), biotin and pantothenic acid were analyzed in 1,800 samples.
      Amino acids (~800) and proteins (alpha-lactoalbumin, beta-casein, and
      lactoferrin) were analyzed. In addition, serum retinol and carotenoids, 25(OH)D,
      vitamin B-12, folic acid, ferritin and biochemical indicators (n=1,200 to 2,000)
      were analysed in the lactating women who provided the breast milk. Ongoing work:
      Fatty acids (C4-C24), fatsoluble vitamins and carotenoids, are on-going analysis.
      CONCLUSIONS: A regional breast milk compositional database is at an advanced
      stage of development in China with the intention that it be available on-line.

PMID- 27702727
TI  - An internet-based food frequency questionnaire for a large Chinese population.
AB  - BACKGROUND AND OBJECTIVES: National dietary surveys are needed and difficult to
      conduct in China. The current study aims to develop and validate an internet
      based diet questionnaire for Chinese (IDQC) to assess intakes in Northern China.
      METHODS AND STUDY DESIGN: We recruited 292 city residents by email and telephone
      in Harbin to obtain the IDQC and 3-day diet diaries. The food group and nutrient
      intakes from the IDQC were validated against those from the 3-day diet diaries.
      Paired sample t-tests were used to compare the methodological differences, and
      repeatability was estimated using Pearson's correlations. Cross-classification
      was used to calculate the percentage agreement in quartiles for all food groups
      and nutrients. RESULTS: Positive correlations were found between the IDQC and 3
      day diet diaries for all food groups after energy adjustment (from 0.28 for seeds
      and nuts to 0.63 for dairy products). Positive correlations were observed for all
      nutrients between the IDQC and 3-day diet diaries, with correlations ranging from
      0.37 for folic acid to 0.98 for iodine. The overall agreements for food groups
      and nutrients were above 69.2%, indicating satisfactory consistency between the
      IDQC and 3-day diet diaries. CONCLUSIONS: The IDQC can be used to estimate the
      food and nutrient intakes in a Northern China population for both clinical
      nutrition epidemiological and public health nutritional purposes. The
      questionnaire system IDQC (v1.0) is freely available at
      http://www.yyjy365.org/diet/.

PMID- 27702726
TI  - Obesity, non-communicable disease (NCD) risk factors and dietary factors among
      Chinese school-aged children.
AB  - BACKGROUND AND OBJECTIVES: China's nutrition transition is characterized by
      dramatic increases in overweight and cardiometabolic (CM) risk. The burden of
      obesity, CM risk factors and dietary intake among Chinese children were explored.
      METHODS AND STUDY DESIGN: Children 7-12 y old from the 2009 China Health and
      Nutrition Survey with available dietary intake data, anthropometry, blood
      pressure, and fasting blood samples were included (n=663). CM risk prevalence was
      calculated; logistic regression was used to investigate the association of
      nutrient intakes with CM risk, adjusting for age, gender, physical activity, area
      of residence and income. RESULTS: 14% of Chinese school-aged children and ~20% of
      those from urban areas and higher income households had overweight/obesity
      (p<0.05). The prevalence of prehypertension was ~20% while hypertension was 14%.
      Around 20% of all children and >=30% of those from urban areas and higher income
      households had impaired glucose/ HbA1c (p<0.05). More than half of the studied
      children had pre-dyslipidemia (i.e. at least one lipid measurement above
      borderline levels) and 21% of children had dyslipidemia. Approximately 30% of all
      children had energy intakes above requirements and 38% of them had excessive
      proportions of dietary fat and saturated fat. Children with higher intakes of
      total daily energy and total and added sugars had a greater likelihood of having
      impaired blood pressure and glucose/HbA1c. CONCLUSIONS: Childhood overweight and
      CM risk is prevalent in urban and rural areas of China and across different
      socioeconomic groups although disparities between classes still pervade. Several
      dietary factors such as sugars were significant correlates of CM risk.

PMID- 27702728
TI  - Dietary attitudes and behaviours of women in China after the 2008 Wenchuan
      earthquake in three seismically different zones.
AB  - BACKGROUND AND OBJECTIVES: The sudden occurrence of the 2008 Wenchuan Earthquake
      not only devastated people's health, but also may have impacted on the
      psychological and dietary attitudes and behaviours of the survivors. Although the
      influence of natural disaster on people's health has been extensively
      investigated, there is a lack of information about the effects on people's
      dietary attitudes and behaviours. Our aim was to evaluate the influence of the
      Wenchuan earthquake on the dietary attitudes and behaviours of adult women from
      different zones of China in July 2008. METHODS AND STUDY DESIGN: 736 women, aged
      18-55 years old, were randomly selected and interviewed after the earthquake.
      Women were selected from three zones: the earthquake zone (n=206), the shaking
      zone (n=326), and the non-seismic zone (n=204). RESULTS: Although nutrition
      knowledge mean scores of women in the three zones were relatively low, the women
      in the earthquake zone became more vigilant about the nutritional value and
      acceptability of food than women in the other two zones. Nevertheless, women in
      the earthquake zone also developed some arguably untoward, if understandable,
      behaviour after the disaster. They increased their consumption and tendency to
      stock instant food and snack items. That said, these findings were modulated by
      other factors such as age, residence, Body Mass Index (BMI), and nutrition
      knowledge itself, as were post-earthquake eating behaviours, as judged by the
      ordinal logistic regression analyses performed. CONCLUSIONS: The major Wenchuan
      earthquake was associated with differentials in dietary attitudes and behaviours
      among women by seismic zone.

PMID- 27702729
TI  - Comparison of the prevalence and characteristics of food hypersensitivity among
      adolescent and older women.
AB  - BACKGROUND AND OBJECTIVES: Although food hypersensitivity is a public health
      concern, its documentation among the elderly is limited. The current study aims
      to compare the prevalence and characteristics of food hypersensitivity among
      adolescent women between aged 18-24 with among older women >50 years of age.
      METHODS AND STUDY DESIGN: 660 female university students between the ages of 18
      and 24 who volunteered were enrolled as adolescent subjects. 470 women >50 years
      old who visited the Health Care Centre of Kyoto Katsura Hospital for health check
      ups were enrolled as the older subjects. A questionnaire created by ourselves
      asking the presence of food hypersensitivity, symptoms, causative food, personal
      or family history of other allergic disorders was distributed. RESULTS: The
      prevalence of food hypersensitivity was statistically similar between adolescent
      (8.2%) and older women (8.9%). Among them, only 24.1% of the adolescent women and
      26.2% of the older women had been diagnosed by physicians as having food allergy.
      The main causative foods (fruits, shellfish and fish) and the manifestations
      relating to food hypersensitivity were almost identical between adolescent and
      older women. In both adolescent and older women, food hypersensitivity positive
      group showed significantly higher prevalence of personal or family history of
      allergic disorders than that in food hypersensitivity negative group.
      CONCLUSIONS: These data indicate that food hypersensitivity in older women should
      be given more attention because the prevalence of this condition was as common as
      that in adolescent women.

PMID- 27702730
TI  - Middle-class household food providers' views and experiences of food marketing in
      Vietnam.
AB  - BACKGROUND AND OBJECTIVES: Food marketing has been identified as a target for
      intervention in the prevention of childhood overweight and obesity within
      countries and globally, and promotion of healthy diets has been classified as a
      key strategy to reduce the burden of non-communicable diseases and health
      inequalities. The present study aims to investigate how Vietnamese middle-class
      household food providers are impacted by food advertising communications, their
      views of food marketing and the ways they think the government can control food
      marketing to assist people to consume healthier diets. METHODS AND STUDY DESIGN:
      810 household food providers participated in the online survey. Frequency counts
      were calculated using IBM SPSS version 21. RESULTS: Many respondents had been
      exposed to food marketing; 82.8% had seen food advertising in magazines at least
      once a month, 65.1% had received free food samples in public places, 68.0% had
      received food advertising information via email. Many household food providers
      appeared to support food marketing; 73.3% approved of nutrition education in
      schools or on television being provided by soft drink or fast food companies,
      63.7% supported the marketing of infant formula milk. There were mixed views
      about what actions the government could implement to control food marketing;
      88.2% supported clearer food content on food labels, 84.1% believed that children
      should learn how to purchase and cook foods at school. CONCLUSIONS: A substantial
      majority of Vietnamese middle-class household food providers appeared unaware of
      the adverse effects of food marketing. Education and policy leadership in food
      and nutrition are urgently required.

PMID- 27702731
TI  - Salty food preference is associated with osteoporosis among Chinese men.
AB  - BACKGROUND AND OBJECTIVES: The main purpose of this study was to evaluate the
      associations between salty food preference and osteoporosis (OP) in general
      Chinese men. METHODS AND STUDY DESIGN: We conducted a largescale, community
      based, cross-sectional study to estimate the associations by using self-report
      questionnaire to evaluate the salty food preference. The total of 1,092 men was
      available to data analysis in this study. Multiple regression models controlling
      for confounding factors to include salty food preference variables were employed
      to explore the relationships for OP. RESULTS: We found negative correlations
      between preference for salty food and T-score (p=0.006). Multiple regression
      analysis showed that the preference for salty food was significantly positively
      associated with OP (p<0.05 for all). The men with preference for salty food
      habits had a higher prevalence of OP. CONCLUSION: The findings indicated that
      salty food preference was independently and significantly associated with OP. The
      prevalence of OP was more frequent in Chinese men preferring salty food habits.

PMID- 27702732
TI  - Comparison of salt taste thresholds and salt usage behaviours between adults in
      Myanmar and Korea.
AB  - BACKGROUND AND OBJECTIVES: Excessive oral salt intake can induce hypertension.
      According to previous studies, the prevalence of hypertension is higher in
      Myanmar than in Korea. We postulated that Myanmar adults had higher salt taste
      thresholds and eat much saltier food. This study aimed to compare salt taste
      thresholds and salt usage behaviour scores between adults in Myanmar and Korea.
      METHODS AND STUDY DESIGN: This cross-sectional study enrolled patients who
      visited volunteer medical service clinics at Ansung in Korea and Hlegu and Bago
      in Myanmar in August 2014. We measured the vital signs, heights, and weights of
      each patient and evaluated detection thresholds, recognition thresholds, and salt
      preferences. All patients underwent urinalysis and spot urine Na tests.
      Additionally, they each completed a salt usage behaviour questionnaire. RESULTS:
      A total of 131 patients were enrolled, including 64 Myanmarese patients and 67
      Korean patients. Blood pressure was significantly higher in the Myanmarese than
      in the Koreans. Detection and recognition thresholds, salt preferences, and spot
      urine sodium and salt usage behaviour scores were also higher in the Myanmarese
      than in the Korean subjects. We calculated correlation coefficients between
      systolic blood pressure and parameters that were related to salt intake. The
      detection and recognition thresholds were significantly correlated with systolic
      blood pressure. CONCLUSION: All parameters related to salt intake, including
      detection and recognition thresholds, salt preference, salt usage behaviour
      scores and spot urine sodium concentrations, are significantly higher in
      Myanmarese than in Korean individuals.

PMID- 27702733
TI  - Vitamin D status of Maori and non-Maori octogenarians in New Zealand: a Cohort
      Study (LiLACS NZ).
AB  - BACKGROUND AND OBJECTIVES: This study assessed vitamin D status and its
      determinants in a cohort of octogenarians living within New Zealand's Bay of
      Plenty and Lakes Districts. METHODS AND STUDY DESIGN: Serum 25- hydroxyvitamin D
      [25(OH)D] concentration was measured in 209 Maori (aged 80-90 years) and 357 non
      Maori (85 years), along with demographic, lifestyle, supplement use and other
      health data. RESULTS: Mean [95% CI] 25(OH)D concentration was 69 [67 to 72]
      nmol/L, with 15% >100 nmol/L and 6 individuals >150 nmol/L. Concentrations in
      Maori (59 [55 to 62] 4 nmol/L) were lower than in non-Maori (75 [72 to 78]
      nmol/L; p<0.001), a difference maintained when adjusted for day-of-year measured.
      Vitamin D supplementation was reported by 98 participants (18%): including a
      greater proportion of women (24%) than men (11%; p<0.001) and of non-Maori (24%)
      than Maori (7%; p<0.001). Of those taking vitamin D, 49% took high oral doses
      (>=25 MUg/day or equivalent) and five individuals took >50 MUg/day. Vitamin D
      supplement use strongly and independently predicted seasonally- adjusted 25(OH)D
      concentration and was associated with 28 nmol/L higher levels than non-use. Other
      predictors included Maori ethnicity (10 nmol/L lower concentration than for non
      Maori), and female gender (11 nmol/L lower). CONCLUSIONS: Vitamin D status in New
      Zealand octogenarians appears higher than previously reported, particularly in
      non-Maori compared to Maori. Prescribed and non-prescribed oral vitamin D
      supplementation is prevalent in this group and a strong indicator of vitamin D
      status.

PMID- 27702734
TI  - The physical examination content of the Japanese National Health and Nutrition
      Survey: temporal changes.
AB  - BACKGROUND AND OBJECTIVES: Survey items of the Japan National Nutrition Survey (J
      NNS) have changed over time. Several papers on dietary surveys have been
      published; however, to date, there are no in-depth papers regarding physical
      examinations. Therefore, we investigated changes in the survey items in the
      physical examinations performed in the J-NNS and the National Health and
      Nutrition Survey (NHNS), with the aim of incorporating useful data for future
      policy decisions. METHODS AND STUDY DESIGN: We summarized the description of
      physical examinations and marshalled the changes of survey items from the J-NNS
      and NHNS from 1946 to 2012. The physical examination is roughly classified into
      the following six components: some are relevant to anthropometric measurements,
      clinical measurements, physical symptoms, blood tests, lifestyle and medication
      by interview, and others. RESULTS: Items related to nutritional deficiency, such
      as anaemia and tendon reflex disappearance, and body weight measurements were
      collected during the early period, according to the instructions of the General
      Headquarters. From 1989, blood tests and measurement of physical activity were
      added, and serum total protein, total cholesterol, triglycerides, HDL
      cholesterol, blood glucose, red blood corpuscles and haemoglobin measurements
      have been performed continuously for more than 20 years. CONCLUSIONS: This is the
      first report on the items of physical examination in the J-NNS and NHNS. Our
      research results provide basic information for the utilization of the J-NNS and
      NHNS, to researchers, clinicians or policy makers. Monitoring the current state
      correctly is essential for national health promotion, and also for improvement of
      the investigation methods to apply country-by-country comparisons.

PMID- 27702735
TI  - Endemic fluorosis in Henan province, China: ERalpha gene polymorphisms and
      reproductive hormones among women.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to explore the influence of
      fluoride exposure and ERalpha gene polymorphisms on reproductive hormone
      concentrations of women in accordance with endemic fluorosis residence. METHODS
      AND STUDY DESIGN: A cross sectional study was conducted in Tongxu county, Henan
      Province, China. A total of 679 women were recruited using cluster sampling and
      each subject provided fasting blood and an associated urine sample. We measured
      the concentrations of serum gonadotropin releasing hormone (GnRH), follicle
      stimulating hormone, luteinizing hormone, and estradiol and urinary fluoride.
      RESULTS: In the defluoridation project group (DFPG), serum GnRH was lower in
      women carrying C/C genotype compared to in those carrying C/T and T/T genotypes
      of ERalpha gene rs3798577 (p<0.05). In the endemic fluorosis group (EFG), serum
      GnRH was lower in women carrying Pp genotype compared to in those carrying PP and
      pp genotypes of ERalpha PvuII (p<0.05). Serum GnRH in women from EFG who carried
      Pp, pp, Xx and xx genotypes in ERalpha gene PvuII and XbaI was lower than in
      those in the control group (CG) who carried same genotypes (p<0.05). Furthermore,
      serum GnRH in women from EFG was significantly lower than in those in CG,
      regardless of whether the women were carrying C/C, C/T or T/T genotypes of
      ERalpha rs3798577 (p<0.05). Serum estradiol concentrations in EFG were
      significantly lower than in CG when the women were carrying the Pp, Xx and T/T
      genotypes in ERalpha gene (p<0.05). CONCLUSION: Interaction of ERalpha gene and
      fluoride exposure may influence women's serum reproductive hormone
      concentrations.

PMID- 27702737
TI  - Usability Evaluation Methods for Gesture-Based Games: A Systematic Review.
AB  - BACKGROUND: Gestural interaction systems are increasingly being used, mainly in
      games, expanding the idea of entertainment and providing experiences with the
      purpose of promoting better physical and/or mental health. Therefore, it is
      necessary to establish mechanisms for evaluating the usability of these
      interfaces, which make gestures the basis of interaction, to achieve a balance
      between functionality and ease of use. OBJECTIVE: This study aims to present the
      results of a systematic review focused on usability evaluation methods for
      gesture-based games, considering devices with motion-sensing capability. We
      considered the usability methods used, the common interface issues, and the
      strategies adopted to build good gesture-based games. METHODS: The research was
      centered on four electronic databases: IEEE, Association for Computing Machinery
      (ACM), Springer, and Science Direct from September 4 to 21, 2015. Within 1427
      studies evaluated, 10 matched the eligibility criteria. As a requirement, we
      considered studies about gesture-based games, Kinect and/or Wii as devices, and
      the use of a usability method to evaluate the user interface. RESULTS: In the 10
      studies found, there was no standardization in the methods because they
      considered diverse analysis variables. Heterogeneously, authors used different
      instruments to evaluate gesture-based interfaces and no default approach was
      proposed. Questionnaires were the most used instruments (70%, 7/10), followed by
      interviews (30%, 3/10), and observation and video recording (20%, 2/10).
      Moreover, 60% (6/10) of the studies used gesture-based serious games to evaluate
      the performance of elderly participants in rehabilitation tasks. This highlights
      the need for creating an evaluation protocol for older adults to provide a user
      friendly interface according to the user's age and limitations. CONCLUSIONS:
      Through this study, we conclude this field is in need of a usability evaluation
      method for serious games, especially games for older adults, and that the
      definition of a methodology and a test protocol may offer the user more comfort,
      welfare, and confidence.

PMID- 27702736
TI  - A huge ovarian mucinous cystadenoma associated with contralateral teratoma and
      polycystic ovary syndrome in an obese adolescent girl.
AB  - A 13-year-old, obese girl presented with acute abdominal pain with abdominal
      distension for a year. The physical examination revealed marked abdominal
      distension with a large well-circumscribed mass sized 13*20 cm. Her body mass
      index (BMI) was 37.8 kg/m2. An abdominal CT scan revealed a huge multiloculated
      cystic mass and a left adnexal mass. She had an abnormal fasting plasma glucose
      and low HDL-C. Laparotomy, right salpingooophorectomy, left cystectomy, lymph
      node biopsies and partial omentectomy were performed. The left ovary demonstrated
      multiple cystic follicles over the cortex. The histologic diagnosis was a
      mucinous cystadenoma of the right ovary and a matured cystic teratoma of the left
      ovary. Both obesity and polycystic ovary syndrome (PCOS) are associated with a
      greater risk of ovarian tumours, where PCOS could be either the cause or as a
      consequence of an ovarian tumour. We report an obese, perimenarchal girl with
      bilateral ovarian tumours coexistent with a polycystic ovary and the metabolic
      syndrome.

PMID- 27702738
TI  - Health Literacy and Health Information Technology Adoption: The Potential for a
      New Digital Divide.
AB  - BACKGROUND: Approximately one-half of American adults exhibit low health literacy
      and thus struggle to find and use health information. Low health literacy is
      associated with negative outcomes including overall poorer health. Health
      information technology (HIT) makes health information available directly to
      patients through electronic tools including patient portals, wearable technology,
      and mobile apps. The direct availability of this information to patients,
      however, may be complicated by misunderstanding of HIT privacy and information
      sharing. OBJECTIVE: The purpose of this study was to determine whether health
      literacy is associated with patients' use of four types of HIT tools: fitness and
      nutrition apps, activity trackers, and patient portals. Additionally, we sought
      to explore whether health literacy is associated with patients' perceived ease of
      use and usefulness of these HIT tools, as well as patients' perceptions of
      privacy offered by HIT tools and trust in government, media, technology
      companies, and health care. This study is the first wide-scale investigation of
      these interrelated concepts. METHODS: Participants were 4974 American adults
      (n=2102, 42.26% male, n=3146, 63.25% white, average age 43.5, SD 16.7 years).
      Participants completed the Newest Vital Sign measure of health literacy and
      indicated their actual use of HIT tools, as well as the perceived ease of use and
      usefulness of these applications. Participants also answered questions regarding
      information privacy and institutional trust, as well as demographic items.
      RESULTS: Cross-tabulation analysis indicated that adequate versus less than
      adequate health literacy was significantly associated with use of fitness apps
      (P=.02), nutrition apps (P<.001), activity trackers (P<.001), and patient portals
      (P<.001). Additionally, greater health literacy was significantly associated with
      greater perceived ease of use and perceived usefulness across all HIT tools after
      controlling for demographics. Regarding privacy perceptions of HIT and
      institutional trust, patients with greater health literacy often demonstrated
      decreased privacy perceptions for HIT tools including fitness apps (P<.001) and
      nutrition apps (P<.001). Health literacy was negatively associated with trust in
      government (P<.001), media (P<.001), and technology companies (P<.001).
      Interestingly, health literacy score was positively associated with trust in
      health care (P=.03). CONCLUSIONS: Patients with low health literacy were less
      likely to use HIT tools or perceive them as easy or useful, but they perceived
      information on HIT as private. Given the fast-paced evolution of technology,
      there is a pressing need to further the understanding of how health literacy is
      related to HIT app adoption and usage. This will ensure that all users receive
      the full health benefits from these technological advances, in a manner that
      protects health information privacy, and that users engage with organizations and
      providers they trust.

PMID- 27702739
TI  - Margaret McCartney: Publishing doctors' private earnings is not enough.

PMID- 27702740
TI  - Neuro-cognitive mechanisms of simultanagnosia in patients with posterior cortical
      atrophy.
AB  - Posterior cortical atrophy is dominated by progressive degradation of parieto
      occipital grey and white matter, and represents in most cases a variant of
      Alzheimer's disease. Patients with posterior cortical atrophy are characterized
      by increasing higher visual and visuo-spatial impairments. In particular, a key
      symptom of posterior cortical atrophy is simultanagnosia i.e. the inability to
      perceive multiple visual objects at the same time. Two neuro-cognitive mechanisms
      have been suggested to underlie simultanagnosia, either reduced visual short-term
      memory capacity or decreased visual processing speed possibly resulting from
      white matter impairments over and above damage to cortical brain areas. To test
      these distinct hypotheses, we investigated a group of 12 patients suffering from
      posterior cortical atrophy with homogenous lesion sides in parieto-occipital
      cortices and varying severity of grey and white matter loss. More specifically,
      we (i) tested whether impaired short-term memory capacity or processing speed
      underlie symptoms of simultanagnosia; (ii) assessed the link to grey and white
      matter damage; and (iii) integrated those findings into a neuro-cognitive model
      of simultanagnosia in patients with posterior cortical atrophy. To this end,
      simultaneous perception of multiple visual objects was tested in patients with
      posterior cortical atrophy mostly with positive Alzheimer's disease biomarkers
      and healthy age-matched controls. Critical outcome measures were identification
      of overlapping relative to non-overlapping figures and visuo-spatial performance
      in tests sensitive to simultanagnosia. Using whole report of briefly presented
      letter arrays based on the mathematically formulated 'Theory of Visual
      Attention', we furthermore quantified parameters of visual short-term memory
      capacity and visual processing speed. Grey and white matter atrophy was assessed
      by voxel-based morphometry analyses of structural magnetic resonance data. All
      patients showed severe deficits of simultaneous perception. Compared to controls,
      we observed a specific slowing of visual processing speed, while visual short
      term memory capacity was preserved. In a regression analysis, processing speed
      was identified as the only significant predictor of simultaneous perception
      deficits that explained a high degree of variance (70-82%) across simultanagnosia
      tasks. More severe slowing was also indicative for more severe impairments in
      reading and scene comprehension. Voxel-based morphometry yielded extensive
      reductions of grey and white matter in parieto-occipital and thalamic brain
      areas. Importantly, the degree of individual atrophy of white matter in left
      superior parietal lobe, but not of any grey matter region, was associated with
      processing speed. Based on these findings, we propose that atrophy of white
      matter commonly observed in posterior cortical atrophy leads to slowing of visual
      processing speed, which underlies the overt clinical symptoms of simultanagnosia.

PMID- 27702742
TI  - South African doctors protest long shifts by wearing coloured wristbands.

PMID- 27702741
TI  - Cognitive behavioural therapy cuts GP visits by frequent attenders, finds study.

PMID- 27702743
TI  - Junior doctors' dispute leaves big questions about state of NHS.

PMID- 27702744
TI  - Japanese cellular biologist wins Nobel prize for study of autophagy.

PMID- 27702747
TI  - Prolonged sitting negatively affects the postprandial plasma triglyceride
      lowering effect of acute exercise.
AB  - The interaction of prolonged sitting with physical exercise for maintaining
      health is unclear. We tested the hypothesis that prolonged siting would have a
      deleterious effect on postprandial plasma lipemia (PPL, postprandial plasma
      triglycerides) and reduce the ability of an acute exercise bout to attenuate PPL.
      Seven healthy young men performed three, 5-day interventions [days 1-5 (D1-D5)]
      in a randomized crossover design with >1 wk between interventions: 1) sitting >
      14 h/day with hypercaloric energy balance (SH), 2) sitting >14 h/day with net
      energy balance (SB), and 3) active walking/standing with net energy balance (WB)
      and sitting 8.4 h/day. The first high-fat tolerance test (HFTT1) was performed on
      D3 following 2 days of respective interventions. On the evening of D4 subjects
      ran on a treadmill for 1 h at ~67% Vo2max, followed by the second HFTT (HFTT2) on
      D5. Two days of prolonged sitting increased TG AUCI (i.e., incremental area under
      the curve for TG), irrespective of energy balance, compared with WB (27% in SH, P
      = 0.003 and 26% in SB, P = 0.046). Surprisingly, after 4 days of prolonged
      sitting (i.e.; SH and SB), the acute exercise on D4 failed to attenuate TG AUCI
      or increase relative fat oxidation in HFTT2, compared with HFTT1, regardless of
      energy balance. In conclusion, prolonged sitting over 2-4 days was sufficient to
      amplify PPL, which was not attenuated by acute exercise, regardless of energy
      balance. This underscores the importance of limiting sitting time even in people
      who have exercised.

PMID- 27702748
TI  - Healthcare professionals must lead on climate change.

PMID- 27702745
TI  - Estimation of Inorganic Arsenic Exposure in Populations With Frequent Seafood
      Intake: Evidence From MESA and NHANES.
AB  - The sum of urinary inorganic arsenic (iAs) and methylated arsenic
      (monomethylarsonate and dimethylarsinate (DMA)) species is the main biomarker of
      iAs exposure. Assessing iAs exposure, however, is difficult in populations with
      moderate-to-high seafood intakes. In the present study, we used subsamples from
      the Multi-Ethnic Study of Atherosclerosis (2000-2002) (n = 310) and the 2003-2006
      National Health and Nutrition Examination Survey (n = 1,175). We calibrated
      urinary concentrations of non-seafood-derived iAs, DMA, and methylarsonate, as
      well as the sum of inorganic and methylated arsenic species, in the Multi-Ethnic
      Study of Atherosclerosis and of DMA in the National Health and Nutrition
      Examination Survey by regressing their original concentrations by arsenobetaine
      and extracting model residuals. To confirm that calibrated biomarkers reflected
      iAs exposure but not seafood intake, we compared urinary arsenic concentrations
      by levels of seafood and rice intakes. Self-reported seafood intakes, estimated n
      3 polyunsaturated fatty acid levels, and measured n-3 polyunsaturated fatty acid
      levels were positively associated with the original urinary arsenic biomarkers.
      Using the calibrated arsenic biomarkers, we found a marked attenuation of the
      associations with self-reported seafood intake and estimated or measured n-3
      fatty acids, whereas associations with self-reported rice intake remained
      similar. Our residual-based method provides estimates of iAs exposure and
      metabolism for each participant that no longer reflect seafood intake and can
      facilitate research about low-to-moderate levels of iAs exposure in populations
      with high seafood intakes.

PMID- 27702746
TI  - Caspase-1 deficiency promotes high-fat diet-induced adipose tissue inflammation
      and the development of obesity.
AB  - Caspase-1 is a cysteine protease responsible for the processing of the
      proinflammatory cytokine interleukin-1beta and activated by the formation of
      inflammasome complexes. Although several investigations have found a link between
      diet-induced obesity and caspase-1, the relationship remains controversial. Here,
      we found that mice deficient in caspase-1 were susceptible to high-fat diet
      induced obesity with increased adiposity as well as normal lipid and glucose
      metabolism. Caspase-1 deficiency clearly promoted the infiltration of
      inflammatory macrophages and increased the production of C-C motif chemokine
      ligand 2 (CCL2) in the adipose tissue. The dominant cellular source of CCL2 was
      stromal vascular fraction rather than adipocytes in the adipose tissue. These
      findings demonstrate a critical role of caspase-1 in macrophage-driven
      inflammation in the adipose tissue and the development of obesity. These data
      provide novel insights into the mechanisms underlying inflammation in the
      pathophysiology of obesity.

PMID- 27702749
TI  - Toll-Like Receptors, Hypertension, and an Antimalarial Drug.

PMID- 27702750
TI  - Beulah Bewley - My Life as a Woman and Doctor.

PMID- 27702754
TI  - SNP synteny analysis of Staphylococcus aureus and Pseudomonas aeruginosa
      population genomics.
AB  - Genomic sequence diversity of a bacterial species mainly results from the
      frequency distribution of single nucleotide polymorphisms (SNPs). Here we report
      on a SNP-matrix based binary algorithm to determine the intra- or interclonal
      genomic diversity by the number of shared sequential SNPs, the so-called SNP
      synteny or haplotype. All SNP positions and the frequency and length distribution
      of haplotypes are determined from pairwise alignment of completely sequenced
      genomes. This metric is invariant regarding the reference genome chosen.
      Information is obtained about the size of haplotypes, genomic gradients of
      recombination frequency, relatedness of strains and population composition of a
      taxon or clonal populations. The approach is illustrated with whole genome data
      sets of Staphylococcus aureus and Pseudomonas aeruginosa strains.

PMID- 27702753
TI  - Fractionation of sulfur and hydrogen isotopes in Desulfovibrio vulgaris with
      perturbed DsrC expression.
AB  - Dissimilatory sulfate reduction is the central microbial metabolism in global
      sulfur cycling. Understanding the importance of sulfate reduction to Earth's
      biogeochemical S cycle requires aggregating single-cell processes with
      geochemical signals. For sulfate reduction, these signals include the ratio of
      stable sulfur isotopes preserved in minerals, as well as the hydrogen isotope
      ratios and structures of microbial membrane lipids preserved in organic matter.
      In this study, we cultivated the model sulfate reducer, Desulfovibrio vulgaris
      DSM 644T, to investigate how these parameters were perturbed by changes in
      expression of the protein DsrC. DsrC is critical to the final metabolic step in
      sulfate reduction to sulfide. S and H isotopic fractionation imposed by the wild
      type was compared to three mutants. Discrimination against 34S in sulfate, as
      calculated from the residual reactant, did not discernibly differ among all
      strains. However, a closed-system sulfur isotope distillation model, based on
      accumulated sulfide, produced inconsistent results in one mutant strain IPFG09.
      Lipids produced by IPFG09 were also slightly enriched in 2H. These results
      suggest that DsrC alone does not have a major impact on sulfate-S, though may
      influence sulfide-S and lipid-H isotopic compositions. While intriguing, a
      mechanistic explanation requires further study under continuous culture
      conditions.

PMID- 27702751
TI  - Patient-derived tumour xenografts for breast cancer drug discovery.
AB  - Despite remarkable advances in our understanding of the drivers of human
      malignancies, new targeted therapies often fail to show sufficient efficacy in
      clinical trials. Indeed, the cost of bringing a new agent to market has risen
      substantially in the last several decades, in part fuelled by extensive reliance
      on preclinical models that fail to accurately reflect tumour heterogeneity. To
      halt unsustainable rates of attrition in the drug discovery process, we must
      develop a new generation of preclinical models capable of reflecting the
      heterogeneity of varying degrees of complexity found in human cancers. Patient
      derived tumour xenograft (PDTX) models prevail as arguably the most powerful in
      this regard because they capture cancer's heterogeneous nature. Herein, we review
      current breast cancer models and their use in the drug discovery process, before
      discussing best practices for developing a highly annotated cohort of PDTX
      models. We describe the importance of extensive multidimensional molecular and
      functional characterisation of models and combination drug-drug screens to
      identify complex biomarkers of drug resistance and response. We reflect on our
      own experiences and propose the use of a cost-effective intermediate
      pharmacogenomic platform (the PDTX-PDTC platform) for breast cancer drug and
      biomarker discovery. We discuss the limitations and unanswered questions of PDTX
      models; yet, still strongly envision that their use in basic and translational
      research will dramatically change our understanding of breast cancer biology and
      how to more effectively treat it.

PMID- 27702755
TI  - Polycomb-dependent control of cell fate in adult tissue.

PMID- 27702756
TI  - Hunt aims for fully home grown doctor workforce.

PMID- 27702752
TI  - Emerging data on androgen receptor splice variants in prostate cancer.
AB  - Androgen receptor splice variants are alternatively spliced variants of androgen
      receptor, which are C-terminally truncated and lack the canonical ligand-binding
      domain. Accumulating evidence has indicated a significant role of androgen
      receptor splice variants in mediating resistance of castration-resistant prostate
      cancer to current therapies and in predicting therapeutic responses. As such,
      there is an urgent need to target androgen receptor splicing variants for more
      effective treatment of castration-resistant prostate cancer. Identification of
      precise and critical targeting points to deactivate androgen receptor splicing
      variants relies on a deep understanding of how they are generated and the
      mechanisms of their action. In this review, we will focus on the emerging data on
      their generation, clinical significance and mechanisms of action as well as the
      therapeutic influence of these findings.

PMID- 27702759
TI  - World Bank president leads charge against stunting.

PMID- 27702757
TI  - Bleeding risk higher with rivaroxaban than dabigatran for stroke prevention, head
      to-head trial shows.

PMID- 27702760
TI  - Bidirectional regulation of fragile X mental retardation protein phosphorylation
      controls rhodopsin homoeostasis.
AB  - Homoeostatic regulation of the light sensor, rhodopsin, is critical for the
      maintenance of light sensitivity and survival of photoreceptors. The major fly
      rhodopsin, Rh1, undergoes light-induced endocytosis and degradation, but its
      protein and mRNA levels remain constant during light/dark cycles. It is not clear
      how translation of Rh1 is regulated. Here, we show that adult photoreceptors
      maintain a constant, abundant quantity of ninaE mRNA, which encodes Rh1. We
      demonstrate that the Fmr1 protein associates with ninaE mRNA and represses its
      translation. Further, light exposure triggers a calcium-dependent
      dephosphorylation of Fmr1, which relieves suppression of Rh1 translation. We
      demonstrate that Mts, the catalytic subunit of protein phosphatase 2A (PP2A),
      mediates light-induced Fmr1 dephosphorylation in a regulatory B subunit of PP2A
      (CKa)-dependent manner. Finally, we show that blocking light-induced Rh1
      translation results in reduced light sensitivity. Our results reveal the
      molecular mechanism of Rh1 homoeostasis and physiological consequence of Rh1
      dysregulation.

PMID- 27702761
TI  - SENP1 regulates IFN-gamma-STAT1 signaling through STAT3-SOCS3 negative feedback
      loop.
AB  - Interferon-gamma (IFN-gamma) triggers macrophage for inflammation response by
      activating the intracellular JAK-STAT1 signaling. Suppressor of cytokine
      signaling 1 (SOCS1) and protein tyrosine phosphatases can negatively modulate IFN
      gamma signaling. Here, we identify a novel negative feedback loop mediated by
      STAT3-SOCS3, which is tightly controlled by SENP1 via de-SUMOylation of protein
      tyrosine phosphatase 1B (PTP1B), in IFN-gamma signaling. SENP1-deficient
      macrophages show defects in IFN-gamma signaling and M1 macrophage activation.
      PTP1B in SENP1-deficient macrophages is highly SUMOylated, which reduces PTP1B
      induced de-phosphorylation of STAT3. Activated STAT3 then suppresses STAT1
      activation via SOCS3 induction in SENP1-deficient macrophages. Accordingly, SENP1
      deficient macrophages show reduced ability to resist Listeria monocytogenes
      infection. These results reveal a crucial role of SENP1-controlled STAT1 and
      STAT3 balance in macrophage polarization.

PMID- 27702762
TI  - Attenuation of carotid neointimal formation after direct delivery of a
      recombinant adenovirus expressing glucagon-like peptide-1 in diabetic rats.
AB  - AIMS: Enhancement of glucagon-like peptide-1 (GLP-1) reduces glucose levels and
      preserves pancreatic beta-cell function, but its effect against restenosis is
      unknown. METHODS AND RESULTS: We investigated the effect of subcutaneous
      injection of exenatide or local delivery of a recombinant adenovirus expressing
      GLP-1 (rAd-GLP-1) into carotid artery, in reducing the occurrence of restenosis
      following balloon injury. As a control, we inserted beta-galactosidase cDNA in
      the same vector (rAd-betaGAL). Otsuka Long-Evans Tokushima rats were assigned to
      three groups (n = 12 each): (1) normal saline plus rAd-betaGAL delivery (NS + rAd
      betaGAL), (2) exenatide plus rAd-betaGAL delivery (Exenatide + rAd-betaGAL), and
      (3) normal saline plus rAd-GLP-1 delivery (NS + rAd-GLP-1). Normal saline or
      exenatide were administered subcutaneously from 1 week before to 2 weeks after
      carotid injury. After 3 weeks, the NS + rAd-betaGAL group showed the highest
      intima-media ratio (IMR; 3.73 +/- 0.90), the exenatide + rAd-betaGAL treatment
      was the next highest (2.80 +/- 0.51), and NS + rAd-GLP-1 treatment showed the
      lowest IMR (1.58 +/- 0.48, P < 0.05 vs. others). The proliferation and migration
      of vascular smooth muscle cells and monocyte adhesion were decreased
      significantly after rAd-GLP-1 treatment, showing the same overall patterns as the
      IMR. In injured vessels, the apoptosis was greater and MMP2 expression was less
      in the NS + rAd-GLP-1 than in the exenatide or rAd-betaGAL groups. In vitro
      expressions of matrix metalloproteinases-2 and monocyte chemoattractant protein-1
      and nuclear factor-kappa-B-p65 translocation were decreased more in the NS + rAd
      GLP-1 group than in the other two groups (all P < 0.05). CONCLUSION: Direct GLP-1
      overexpression showed better protection against restenosis after balloon injury
      via suppression of vascular smooth muscle cell migration, increased apoptosis,
      and decreased inflammatory processes than systemic exenatide treatment. This has
      potential therapeutic implications for treating macrovascular complications in
      diabetes.

PMID- 27702764
TI  - Analysis of bacterial composition in marine sponges reveals the influence of host
      phylogeny and environment.
AB  - Bacterial communities associated with sponges are influenced by environmental
      factors; however, some degree of genetic influence of the host on the microbiome
      is also expected. In this work, 16S rRNA gene amplicon sequencing revealed
      diverse bacterial phylotypes based on the phylogenies of three tropical sponges
      (Aplysina fulva, Aiolochroia crassa and Chondrosia collectrix). Despite their
      sympatric occurrence, the studied sponges presented different bacterial
      compositions that differed from those observed in seawater. However, lower
      dissimilarities in bacterial communities were observed within sponges from the
      same phylogenetic group. The relationships between operational taxonomic units
      (OTUs) recovered from the sponges and database sequences revealed associations
      among sequences from unrelated sponge species and sequences retrieved from
      diverse environmental samples. In addition, one Proteobacteria OTU retrieved from
      A. fulva was identical to sequences previously reported from A. fulva specimens
      collected along the Brazilian coast. Based on these results, we conclude that
      bacterial communities associated with marine sponges are shaped by host identity,
      while environmental conditions seem to be less important in shaping symbiont
      communities. This is the first study to assess bacterial communities associated
      with marine sponges in the remote St. Peter and St. Paul Archipelago using
      amplicon sequencing of the 16S rRNA gene.

PMID- 27702765
TI  - Phylogeographic analyses of bacterial endosymbionts in fig homotomids (Hemiptera:
      Psylloidea) reveal codiversification of both primary and secondary endosymbionts.
AB  - While obligate primary (P-) endosymbionts usually cospeciate with their insect
      hosts, less is known about codiversification of secondary (S-) endosymbionts that
      are generally considered facultative. Typically, insects of the superfamily
      Psylloidea harbour one P- (Carsonella) and at least one S-endosymbiont, thought
      to compensate for Carsonella genome reduction. Most codiversification studies
      have used phylogenies of psyllids and their endosymbionts across and within host
      families or genera, but few have explored patterns within species. We focussed on
      P- and S-endosymbionts of three Mycopsylla (Homotomidae) species to explore
      whether they have congruent phylogenies and within-species geographic structures.
      The P-endosymbiont Carsonella, a S-endosymbiont and Wolbachia all had 100%
      prevalence, while Arsenophonus was only found in one species at low prevalence.
      Congruent phylogenies of Mycopsylla and P-endosymbionts across populations and
      species support strict cospeciation. S-endosymbiont phylogenies were also
      congruent across host species but low genetic variation in the S-endosymbiont was
      not correlated with host phylogeography, possibly due to a shorter evolutionary
      association. Between species, Wolbachia and Mycopsylla phylogenies were
      incongruent, probably due to horizontal transmission events. Our study is the
      first to explore endosymbionts of Mycopsylla and further supports the
      codivergence of Psylloidea hosts and P-endosymbionts, with obligate host
      interactions for both P- and S-endosymbionts.

PMID- 27702766
TI  - Five-Year Optical Coherence Tomography in Patients With ST-Segment-Elevation
      Myocardial Infarction Treated With Bare-Metal Versus Everolimus-Eluting Stents.
AB  - BACKGROUND: The main causes of late (>1 month) stent thrombosis (ST) are stent
      uncoverage, malapposition, and neoatherosclerosis. First-generation drug-eluting
      stents were associated with higher rate of late ST compared with bare-metal
      stents (BMS), especially in patients with ST-segment-elevation myocardial
      infarction. Second-generation everolimus-eluting stents (EES) have shown similar
      rate of late ST than BMS. The aims of the study are to compare the ratio of
      uncovered to total struts per cross-section >=30% and other optical coherence
      tomographic findings associated with ST between EES and BMS in patients with ST
      segment-elevation myocardial infarction at 5 years. METHODS AND RESULTS: One
      hundred and sixty-nine consecutive event-free patients of the randomized
      EXAMINATION study (A Clinical Evaluation of Everolimus Eluting Coronary Stents in
      the Treatment of Patients With ST-Segment Elevation Myocardial Infarction) were
      screened for optical coherence tomographic imaging at 5 years. Patients with
      target vessel-related events or life-threatening comorbidities were excluded.
      Finally, 64 patients (32 EES and 32 BMS) underwent optical coherence tomographic
      imaging. At 5 years, uncovered struts (4.1% versus 1.0%; P<0.01), length of
      uncoverage (3.4 versus 1.4 mm; P=0.02), and ratio of uncovered to total struts
      per cross-section >=30% (35.5% versus 9.7%; P=0.02) were larger with EES than
      that with BMS. Malapposed struts (1.2% versus 0.3%; P=0.02) and malapposition
      length (1.3 versus 0.4 mm; P=0.06) were also larger with EES. Neoatherosclerotic
      plaques (16.1% versus 25.8%; P=0.35) and macrophage accumulations (19.4% versus
      48.4%; P=0.02) were numerically more frequent with BMS. CONCLUSIONS: Despite
      substantial dropout of patients, the healing pattern in event-free ST-segment
      elevation myocardial infarction patients differs between EES and BMS at 5 years.
      EES presented with larger amount of uncovered and malapposed struts and similar
      rate of neoatherosclerosis as compared with BMS. The clinical relevance of these
      findings warrants longer follow-up. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00828087.

PMID- 27702763
TI  - Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic
      conditioning.
AB  - AIMS: Although the nature of the humoral factor which mediates cardioprotection
      established by remote ischaemic conditioning (RIc) remains unknown,
      parasympathetic (vagal) mechanisms appear to play a critical role. As the
      production and release of many gut hormones is modulated by the vagus nerve, here
      we tested the hypothesis that RIc cardioprotection is mediated by the actions of
      glucagon-like peptide-1 (GLP-1). METHODS AND RESULTS: A rat model of myocardial
      infarction (coronary artery occlusion followed by reperfusion) was used. Remote
      ischaemic pre- (RIPre) or perconditioning (RIPer) was induced by 15 min occlusion
      of femoral arteries applied prior to or during the myocardial ischaemia. The
      degree of RIPre and RIPer cardioprotection was determined in conditions of
      cervical or subdiaphragmatic vagotomy, or following blockade of GLP-1 receptors
      (GLP-1R) using specific antagonist Exendin(9-39). Phosphorylation of PI3K/AKT and
      STAT3 was assessed. RIPre and RIPer reduced infarct size by ~50%. In conditions
      of bilateral cervical or subdiaphragmatic vagotomy RIPer failed to establish
      cardioprotection. GLP-1R blockade abolished cardioprotection induced by either
      RIPre or RIPer. Exendin(9-39) also prevented RIPre-induced AKT phosphorylation.
      Cardioprotection induced by GLP-1R agonist Exendin-4 was preserved following
      cervical vagotomy, but was abolished in conditions of M3 muscarinic receptor
      blockade. CONCLUSIONS: These data strongly suggest that GLP-1 functions as a
      humoral factor of remote ischaemic conditioning cardioprotection. This phenomenon
      requires intact vagal innervation of the visceral organs and recruitment of GLP
      1R-mediated signalling. Cardioprotection induced by GLP-1R activation is mediated
      by a mechanism involving M3 muscarinic receptors.

PMID- 27702767
TI  - Editorial Commentary: Influenza Vaccine Effectiveness: A Glass Both Half Full and
      Half Empty.

PMID- 27702769
TI  - Hyperactivation of mammalian target of rapamycin complex 1 by HIV-1 is necessary
      for virion production and latent viral reactivation.
AB  - Generation of new HIV-1 virions requires the constant supply of proteins,
      nucleotides, and energy; however, it is not known which cellular pathways are
      perturbed and what molecular mechanisms are employed. We hypothesized that HIV-1
      may regulate pathways that control synthesis of biomolecules in the cell. In this
      study, we provide evidence that HIV-1 hyperactivates mammalian target of
      rapamycin complex 1 (mTORC1), the central regulator of biosynthesis.
      Mechanistically, we identify the viral regulatory gene tat (transactivator) as
      being responsible for increasing mTORC1 activity in a PI3K-dependent manner.
      Furthermore, we show that hyperactivation of mTORC1 leads to activation of the
      enzyme, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase,
      dihydroorotase, and repression of initiation factor 4E-binding protein 1
      activity. These are regulators of nucleotide biogenesis and protein translation,
      respectively. Moreover, we are able to replicate these results in HIV-1 latent
      cell line models. Finally, we show that inhibition of mTORC1 or PI3K inhibits
      viral replication and viral reactivation as a result of a decrease in
      biosynthesis. Overall, our study identifies a new avenue in HIV-1 biology that
      can lead to development of novel therapeutic targets.-Kumar, B., Arora, S.,
      Ahmed, S., Banerjea, A. C. Hyperactivation of mammalian target of rapamycin
      complex 1 by HIV-1 is necessary for virion production and latent viral
      reactivation.

PMID- 27702771
TI  - Endothelial FAK is required for tumour angiogenesis.

PMID- 27702768
TI  - 2014-2015 Influenza Vaccine Effectiveness in the United States by Vaccine Type.
AB  - BACKGROUND:  Circulating A/H3N2 influenza viruses drifted significantly after
      strain selection for the 2014-2015 vaccines. Also in 2014-2015, the Advisory
      Committee on Immunization Practices recommended preferential use of live
      attenuated influenza vaccine (LAIV) over inactivated influenza vaccine (IIV)
      among children aged 2-8 years. METHODS:  Vaccine effectiveness (VE) across age
      groups and vaccine types was examined among outpatients with acute respiratory
      illness at 5 US sites using a test-negative design, that compared the odds of
      vaccination among reverse transcription polymerase chain reaction-confirmed
      influenza positives and negatives. RESULTS:  Of 9311 enrollees with complete
      data, 7078 (76%) were influenza negative, 1840 (19.8%) were positive for
      influenza A (A/H3N2, n = 1817), and 395 (4.2%) were positive for influenza B
      (B/Yamagata, n = 340). The overall adjusted VE was 19% (95% confidence interval
      [CI], 10% to 27%) and was statistically significant in all age strata except
      those aged 18-64 years. The adjusted VE of 6% (95%CI, -5% to 17%) against A/H3N2
      associated illness was not statistically significant, unlike VE for influenza
      B/Yamagata, which was 55% (95%CI, 43% to 65%). Among those aged 2-8 years, VE
      against A/H3N2 was 15% (95%CI, -16% to 38%) for IIV and -3% (CI, -50% to 29%) for
      LAIV; VE against B/Yamagata was 40% (95%CI, -20% to 70%) for IIV and 74% (95%CI,
      25% to 91%) for LAIV. CONCLUSIONS:  The 2014-2015 influenza vaccines offered
      little protection against the predominant influenza A/H3N2 virus but were
      effective against influenza B. Preferential use of LAIV among young children was
      not supported.

PMID- 27702770
TI  - Impaired sensitivity to pain stimuli in plasma membrane calcium ATPase 2 (PMCA2)
      heterozygous mice: a possible modality- and sex-specific role for PMCA2 in
      nociception.
AB  - Plasma membrane calcium ATPase 2 (PMCA2) is a calcium pump that plays important
      roles in neuronal function. Although it is expressed in pain-associated regions
      of the CNS, including in the dorsal horn (DH), its contribution to pain remains
      undefined. The present study assessed the role of PMCA2 in pain responsiveness
      and the link between PMCA2 and glutamate receptors, GABA receptors (GABARs), and
      glutamate transporters that have been implicated in pain processing in the DH of
      adult female and male PMCA2+/+ and PMCA2+/- mice. Behavioral assays evaluated
      mechanical and thermal pain responsiveness. Mechanical sensitivity was
      significantly increased by 52% and heat sensitivity was reduced by 29% in female,
      but not male, PMCA2+/- mice compared with PMCA2+/+ controls. There were female
      specific changes in metabotropic glutamate receptor 1, NMDA receptor 2A, alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR1,
      GABABR1, and GABABR2 levels, whereas metabotropic glutamate receptor 5, NMDA
      receptor 2B, GluR2, and GABAARalpha2 levels were not altered. Glutamate aspartate
      transporter levels were higher and glial glutamate transporter 1 levels were
      lower in the DH of female, but not male, PMCA2+/- mice. These findings indicate a
      novel role for PMCA2 in modality- and sex-dependent pain responsiveness. Female
      specific molecular changes potentially account for the altered pain responses.
      Khariv, V., Ni, L., Ratnayake, A., Sampath, S., Lutz, B. M., Tao, X.-X., Heary,
      R. F., Elkabes, S. Impaired sensitivity to pain stimuli in plasma membrane
      calcium ATPase 2 (PMCA2) heterozygous mice: a possible modality- and sex-specific
      role for PMCA2 in nociception.

PMID- 27702772
TI  - The Nucleolar Fibrillarin Protein Is Required for Helper Virus-Independent Long
      Distance Trafficking of a Subviral Satellite RNA in Plants.
AB  - RNA trafficking plays pivotal roles in regulating plant development, gene
      silencing, and adaptation to environmental stress. Satellite RNAs (satRNAs),
      parasites of viruses, depend on their helper viruses (HVs) for replication,
      encapsidation, and efficient spread. However, it remains largely unknown how
      satRNAs interact with viruses and the cellular machinery to undergo trafficking.
      Here, we show that the P20 protein of Bamboo mosaic potexvirus satRNA (satBaMV)
      can functionally complement in trans the systemic trafficking of P20-defective
      satBaMV in infected Nicotiana benthamiana The transgene-derived satBaMV,
      uncoupled from HV replication, was able to move autonomously across a graft union
      identified by RT-qPCR, RNA gel blot, and in situ RT-PCR analyses.
      Coimmunoprecipitation experiments revealed that the major nucleolar protein
      fibrillarin is coprecipitated in the P20 protein complex. Notably, silencing
      fibrillarin suppressed satBaMV-, but not HV-, phloem-based movement following
      grafting or coinoculation with HV Confocal microscopy revealed that the P20
      protein colocalized with fibrillarin in the nucleoli and formed punctate
      structures associated with plasmodesmata. The mobile satBaMV RNA appears to exist
      as ribonucleoprotein (RNP) complex composed of P20 and fibrillarin, whereas BaMV
      movement proteins, capsid protein, and BaMV RNA are recruited with HV
      coinfection. Taken together, our findings provide insight into movement of
      satBaMV via the fibrillarin-satBaMV-P20 RNP complex in phloem-mediated systemic
      trafficking.

PMID- 27702774
TI  - Rapid Functional and Sequence Differentiation of a Tandemly Repeated Species
      Specific Multigene Family in Drosophila.
AB  - Gene clusters of recently duplicated genes are hotbeds for evolutionary change.
      However, our understanding of how mutational mechanisms and evolutionary forces
      shape the structural and functional evolution of these clusters is hindered by
      the high sequence identity among the copies, which typically results in their
      inaccurate representation in genome assemblies. The presumed testis-specific,
      chimeric gene Sdic originated, and tandemly expanded in Drosophila melanogaster,
      contributing to increased male-male competition. Using various types of massively
      parallel sequencing data, we studied the organization, sequence evolution, and
      functional attributes of the different Sdic copies. By leveraging long-read
      sequencing data, we uncovered both copy number and order differences from the
      currently accepted annotation for the Sdic region. Despite evidence for pervasive
      gene conversion affecting the Sdic copies, we also detected signatures of two
      episodes of diversifying selection, which have contributed to the evolution of a
      variety of C-termini and miRNA binding site compositions. Expression analyses
      involving RNA-seq datasets from 59 different biological conditions revealed
      distinctive expression breadths among the copies, with three copies being
      transcribed in females, opening the possibility to a sexually antagonistic
      effect. Phenotypic assays using Sdic knock-out strains indicated that should this
      antagonistic effect exist, it does not compromise female fertility. Our results
      strongly suggest that the genome consolidation of the Sdic gene cluster is more
      the result of a quick exploration of different paths of molecular tinkering by
      different copies than a mere dosage increase, which could be a recurrent
      evolutionary outcome in the presence of persistent sexual selection.

PMID- 27702775
TI  - SLiM 2: Flexible, Interactive Forward Genetic Simulations.
AB  - Modern population genomic datasets hold immense promise for revealing the
      evolutionary processes operating in natural populations, but a crucial
      prerequisite for this goal is the ability to model realistic evolutionary
      scenarios and predict their expected patterns in genomic data. To that end, we
      present SLiM 2: an evolutionary simulation framework that combines a powerful,
      fast engine for forward population genetic simulations with the capability of
      modeling a wide variety of complex evolutionary scenarios. SLiM achieves this
      flexibility through scriptability, which provides control over most aspects of
      the simulated evolutionary scenarios with a simple R-like scripting language
      called Eidos. An example SLiM simulation is presented to illustrate the power of
      this approach. SLiM 2 also includes a graphical user interface for simulation
      construction, interactive runtime control, and dynamic visualization of
      simulation output, facilitating easy and fast model development with quick
      prototyping and visual debugging. We conclude with a performance comparison
      between SLiM and two other popular forward genetic simulation packages.

PMID- 27702773
TI  - Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From
      14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic
      Heart Disease Registry (the REMEDY Study).
AB  - BACKGROUND: There are few contemporary data on the mortality and morbidity
      associated with rheumatic heart disease or information on their predictors. We
      report the 2-year follow-up of individuals with rheumatic heart disease from 14
      low- and middle-income countries in Africa and Asia. METHODS: Between January
      2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries
      and followed them for 2 years to assess mortality, congestive heart failure,
      stroke or transient ischemic attack, recurrent acute rheumatic fever, and
      infective endocarditis. RESULTS: Vital status at 24 months was known for 2960
      (88.5%) patients. Two-thirds were female. Although patients were young (median
      age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was
      high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the
      first year and 65.4/1000 patient-years in the second year. Median age at death
      was 28.7 years. Independent predictors of death were severe valve disease (hazard
      ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart
      failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional
      class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95%
      CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at
      enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex
      (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two
      hundred and four (6.9%) patients had new congestive heart failure (incidence,
      38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack
      (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever
      (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000
      patient-years). Previous stroke and older age were independent predictors of
      stroke/transient ischemic attack or systemic embolism. Patients from low- and
      lower-middle-income countries had significantly higher age- and sex-adjusted
      mortality than patients from upper-middle-income countries. Valve surgery was
      significantly more common in upper-middle-income than in lower-middle- or low
      income countries. CONCLUSIONS: Patients with clinical rheumatic heart disease
      have high mortality and morbidity despite being young; those from low- and lower
      middle-income countries had a poorer prognosis associated with advanced disease
      and low education. Programs focused on early detection and the treatment of
      clinical rheumatic heart disease are required to improve outcomes.

PMID- 27702776
TI  - Reconstruction of Haplotype-Blocks Selected during Experimental Evolution.
AB  - The genetic analysis of experimentally evolving populations typically relies on
      short reads from pooled individuals (Pool-Seq). While this method provides
      reliable allele frequency estimates, the underlying haplotype structure remains
      poorly characterized. With small population sizes and adaptive variants that
      start from low frequencies, the interpretation of selection signatures in most
      Evolve and Resequencing studies remains challenging. To facilitate the
      characterization of selection targets, we propose a new approach that
      reconstructs selected haplotypes from replicated time series, using Pool-Seq
      data. We identify selected haplotypes through the correlated frequencies of
      alleles carried by them. Computer simulations indicate that selected haplotype
      blocks of several Mb can be reconstructed with high confidence and low error
      rates, even when allele frequencies change only by 20% across three replicates.
      Applying this method to real data from D. melanogaster populations adapting to a
      hot environment, we identify a selected haplotype-block of 6.93 Mb. We confirm
      the presence of this haplotype-block in evolved populations by experimental
      haplotyping, demonstrating the power and accuracy of our haplotype reconstruction
      from Pool-Seq data. We propose that the combination of allele frequency estimates
      with haplotype information will provide the key to understanding the dynamics of
      adaptive alleles.

PMID- 27702778
TI  - A study on a dental device for the prevention of mucosal dose enhancement caused
      by backscatter radiation from dental alloy during external beam radiotherapy.
AB  - The changes in dose distribution caused by backscatter radiation from a common
      commercial dental alloy (Au-Ag-Pd dental alloy; DA) were investigated to identify
      the optimal material and thicknesses of a dental device (DD) for effective
      prevention of mucositis. To this end, 1 cm3 of DA was irradiated with a 6-MV X
      ray beam (100 MU) in a field size of 10 * 10 cm2 using a Novalis TX linear
      accelerator. Ethylene vinyl acetate copolymer, polyolefin elastomer, and
      polyethylene terephthalate (PET) were selected as DD materials. The depth dose
      along the central axis was determined with respect to the presence/absence of DA
      and DDs at thicknesses of 1-10 mm using a parallel-plate ionization chamber. The
      dose in the absence of DDs showed the lowest value at a distance of 5 mm from the
      DA surface and gradually increased with distance between the measurement point
      and the DA surface for distances of >=5 mm. Except for PET, no significant
      difference between the DA dose curves for the presence and absence of DDs was
      observed. In the dose curve, PET showed a slightly higher dose for DA with DD
      than for DA without DD for thicknesses of >=4 mm. The findings herein suggest
      that the optimal DD material for preventing local dose enhancement of the mucosa
      caused by DA backscatter radiation should have a relatively low atomic number and
      physical density and that optimal DD thickness should be chosen considering
      backscatter radiation and percentage depth dose.

PMID- 27702779
TI  - Pattern of recovery after open reduction and internal fixation of proximal
      phalangeal fractures in the finger: a prospective longitudinal study.
AB  - : The purpose of this study was to determine the pattern of recovery after open
      reduction and internal fixation of proximal phalangeal fractures. A prospective
      longitudinal study of 66 patients who started rehabilitation within 1 week of
      fixation was undertaken. Measures of the level of impairment (range of motion,
      pain, strength), activity limitation (hand use) and return to work were collected
      at Weeks 1, 6, 12 and 26 after operation. Before starting rehabilitation,
      although pain was minimal, the range of motion was severely restricted and there
      was considerable restriction in ability to work. Most of the recovery in range of
      motion, pain, strength, hand use and work participation occurred by Week 6, with
      smaller gains by Week 12 and Week 26. LEVEL OF EVIDENCE: III.

PMID- 27702777
TI  - Loss and Gain of Human Acidic Mammalian Chitinase Activity by Nonsynonymous SNPs.
AB  - Acidic mammalian chitinase (AMCase) is implicated in asthma, allergic
      inflammation, and food processing. Little is known about genetic and evolutional
      regulation of chitinolytic activity of AMCase. Here, we relate human AMCase
      polymorphisms to the mouse AMCase, and show that the highly active variants
      encoded by nonsynonymous single-nucleotide polymorphisms (nsSNPs) are consistent
      with the mouse AMCase sequence. The chitinolytic activity of the recombinant
      human AMCase was significantly lower than that of the mouse counterpart. By
      creating mouse-human chimeric AMCase protein we found that the presence of the N
      terminal region of human AMCase containing conserved active site residues reduced
      the enzymatic activity of the molecule. We were able to significantly increase
      the activity of human AMCase by amino acid substitutions encoded by nsSNPs (N45,
      D47, and R61) with those conserved in the mouse homologue (D45, N47, and M61).
      For abolition of the mouse AMCase activity, introduction of M61R mutation was
      sufficient. M61 is conserved in most of primates other than human and orangutan
      as well as in other mammals. Orangutan has I61 substitution, which also markedly
      reduced the activity of the mouse AMCase, indicating that the M61 is a crucial
      residue for the chitinolytic activity. Altogether, our data suggest that human
      AMCase has lost its chitinolytic activity by integration of nsSNPs during
      evolution and that the enzyme can be reactivated by introducing amino acids
      conserved in the mouse counterpart.

PMID- 27702782
TI  - Blood stem cells: from beginning to end.
AB  - In June 2016, around 200 scientists from all over the world gathered at EMBL
      headquarters in Heidelberg, Germany to discuss the recent advances in
      hematopoietic stem cells from three different angles: developmental, adulthood
      and aging. The meeting, aptly named 'Hematopoietic stem cells: from the embryo to
      the aging organism' also covered cutting-edge technologies applied to this
      subject, such as single-cell analysis, reprogramming and imaging. This Meeting
      review summarizes the exciting work that was presented and covers the main themes
      that emerged from the meeting.

PMID- 27702781
TI  - Differential Phasing between Circadian Clocks in the Brain and Peripheral Organs
      in Humans.
AB  - The daily timing of mammalian physiology is coordinated by circadian clocks
      throughout the body. Although measurements of clock gene expression indicate that
      these clocks in mice are normally in phase with each other, the situation in
      humans remains unclear. We used publicly available data from five studies,
      comprising over 1000 samples, to compare the phasing of circadian gene expression
      in human brain and human blood. Surprisingly, after controlling for age, clock
      gene expression in brain was phase-delayed by ~8.5 h relative to that of blood.
      We then examined clock gene expression in two additional human organs and in
      organs from nine other mammalian species, as well as in the suprachiasmatic
      nucleus (SCN). In most tissues outside the SCN, the expression of clock gene
      orthologs showed a phase difference of ~12 h between diurnal and nocturnal
      species. The exception to this pattern was human brain, whose phasing resembled
      that of the SCN. Our results highlight the value of a multi-tissue, multi-species
      meta-analysis, and have implications for our understanding of the human circadian
      system.

PMID- 27702784
TI  - Ebi modulates wing growth by ubiquitin-dependent downregulation of Crumbs in
      Drosophila.
AB  - Notch signaling at the dorsoventral (DV) boundary is essential for patterning and
      growth of wings in Drosophila The WD40 domain protein Ebi has been implicated in
      the regulation of Notch signaling at the DV boundary. Here we show that Ebi
      regulates wing growth by antagonizing the function of the transmembrane protein
      Crumbs (Crb). Ebi physically binds to the extracellular domain of Crb (Crbext),
      and this interaction is specifically mediated by WD40 repeats 7-8 of Ebi and a
      laminin G domain of Crbext Wing notching resulting from reduced levels of Ebi is
      suppressed by decreasing the Crb function. Consistent with this antagonistic
      genetic relationship, Ebi knockdown in the DV boundary elevates the Crb protein
      level. Furthermore, we show that Ebi is required for downregulation of Crb by
      ubiquitylation. Taken together, we propose that the interplay of Crb expression
      in the DV boundary and ubiquitin-dependent Crb downregulation by Ebi provides a
      mechanism for the maintenance of Notch signaling during wing development.

PMID- 27702783
TI  - Making sense out of spinal cord somatosensory development.
AB  - The spinal cord integrates and relays somatosensory input, leading to complex
      motor responses. Research over the past couple of decades has identified
      transcription factor networks that function during development to define and
      instruct the generation of diverse neuronal populations within the spinal cord. A
      number of studies have now started to connect these developmentally defined
      populations with their roles in somatosensory circuits. Here, we review our
      current understanding of how neuronal diversity in the dorsal spinal cord is
      generated and we discuss the logic underlying how these neurons form the basis of
      somatosensory circuits.

PMID- 27702785
TI  - Inhibition of Shh signalling in the chick wing gives insights into digit
      patterning and evolution.
AB  - In an influential model of pattern formation, a gradient of Sonic hedgehog (Shh)
      signalling in the chick wing bud specifies cells with three antero-posterior
      positional values, which give rise to three morphologically different digits by a
      self-organizing mechanism with Turing-like properties. However, as four of the
      five digits of the mouse limb are morphologically similar in terms of phalangeal
      pattern, it has been suggested that self-organization alone could be sufficient.
      Here, we show that inhibition of Shh signalling at a specific stage of chick wing
      development results in a pattern of four digits, three of which can have the same
      number of phalanges. These patterning changes are dependent on a posterior
      extension of the apical ectodermal ridge, and this also allows the additional
      digit to arise from the Shh-producing cells of the polarizing region - an ability
      lost in ancestral theropod dinosaurs. Our analyses reveal that, if the
      specification of antero-posterior positional values is curtailed, self
      organization can then produce several digits with the same number of phalanges.
      We present a model that may give important insights into how the number of digits
      and phalanges has diverged during the evolution of avian and mammalian limbs.

PMID- 27702786
TI  - cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip
      cell behavior in a Notch-independent manner.
AB  - cAMP-dependent protein kinase A (PKA) is a ubiquitously expressed
      serine/threonine kinase that regulates a variety of cellular functions. Here, we
      demonstrate that endothelial PKA activity is essential for vascular development,
      specifically regulating the transition from sprouting to stabilization of nascent
      vessels. Inhibition of endothelial PKA by endothelial cell-specific expression of
      dominant-negative PKA in mice led to perturbed vascular development, hemorrhage
      and embryonic lethality at mid-gestation. During perinatal retinal angiogenesis,
      inhibition of PKA resulted in hypersprouting as a result of increased numbers of
      tip cells. In zebrafish, cell autonomous PKA inhibition also increased and
      sustained endothelial cell motility, driving cells to become tip cells. Although
      these effects of PKA inhibition were highly reminiscent of Notch inhibition
      effects, our data demonstrate that PKA and Notch independently regulate tip and
      stalk cell formation and behavior.

PMID- 27702789
TI  - Correction: ChtVis-Tomato, a genetic reporter for in vivo visualization of chitin
      deposition in Drosophila.

PMID- 27702791
TI  - Completeness of cancer registry data in a small Iranian province: A capture
      recapture approach.
AB  - BACKGROUND AND OBJECTIVE: The incidence of cancer is rising in Iran, and hence it
      is important to assess the accuracy of the Iranian cancer registry dataset. In
      this study, the completeness of the cancer registry in the Kohgiluyeh and Boyer
      Ahmad (K&B) province is evaluated. METHOD: The data of registered cases of cancer
      of people who were living in the K&B province at the time of diagnosis were
      obtained from the provincial cancer registry offices in K&B, Fars and all other
      neighbouring provinces. A capture-recapture method along with log-linear
      statistical modelling were used for analysis. RESULTS: The results indicated that
      of 2029 known cases of cancer, only 1400 (31%) were registered by the K&B cancer
      registry office. Age-adjusted incidence rates for all common types of cancer rose
      from 307.0 per 100,000 (95% confidence interval (CI); 293.8, 320.3, based on
      observed cases) to 376.4 per 100,000 (95% CI; 361.7, 391.1, based on expected
      number of cases estimated by capture-recapture analysis) ( p < 0.01). The
      completeness of cancer registry data varied significantly for different types of
      cancer. CONCLUSION: Results suggest that the provincial cancer dataset, which is
      a part of the national cancer registry programme, is neither complete nor
      representative. A major improvement in case finding, registry procedures and
      effective data sharing by provincial cancer registry offices is needed in order
      to provide valid data for epidemiology of cancer in Iran.

PMID- 27702788
TI  - Mapping a multiplexed zoo of mRNA expression.
AB  - In situ hybridization methods are used across the biological sciences to map mRNA
      expression within intact specimens. Multiplexed experiments, in which multiple
      target mRNAs are mapped in a single sample, are essential for studying regulatory
      interactions, but remain cumbersome in most model organisms. Programmable in situ
      amplifiers based on the mechanism of hybridization chain reaction (HCR) overcome
      this longstanding challenge by operating independently within a sample, enabling
      multiplexed experiments to be performed with an experimental timeline independent
      of the number of target mRNAs. To assist biologists working across a broad
      spectrum of organisms, we demonstrate multiplexed in situ HCR in diverse imaging
      settings: bacteria, whole-mount nematode larvae, whole-mount fruit fly embryos,
      whole-mount sea urchin embryos, whole-mount zebrafish larvae, whole-mount chicken
      embryos, whole-mount mouse embryos and formalin-fixed paraffin-embedded human
      tissue sections. In addition to straightforward multiplexing, in situ HCR enables
      deep sample penetration, high contrast and subcellular resolution, providing an
      incisive tool for the study of interlaced and overlapping expression patterns,
      with implications for research communities across the biological sciences.

PMID- 27702787
TI  - Complex cis-regulatory landscape of the insulin receptor gene underlies the broad
      expression of a central signaling regulator.
AB  - Insulin signaling plays key roles in development, growth and metabolism through
      dynamic control of glucose uptake, global protein translation and transcriptional
      regulation. Altered levels of insulin signaling are known to play key roles in
      development and disease, yet the molecular basis of such differential signaling
      remains obscure. Expression of the insulin receptor (InR) gene itself appears to
      play an important role, but the nature of the molecular wiring controlling InR
      transcription has not been elucidated. We characterized the regulatory elements
      driving Drosophila InR expression and found that the generally broad expression
      of this gene is belied by complex individual switch elements, the dynamic
      regulation of which reflects direct and indirect contributions of FOXO, EcR, Rbf
      and additional transcription factors through redundant elements dispersed
      throughout ~40 kb of non-coding regions. The control of InR transcription in
      response to nutritional and tissue-specific inputs represents an integration of
      multiple cis-regulatory elements, the structure and function of which may have
      been sculpted by evolutionary selection to provide a highly tailored set of
      signaling responses on developmental and tissue-specific levels.

PMID- 27702792
TI  - How can hospitals better protect the privacy of electronic medical records?
      Perspectives from staff members of health information management departments.
AB  - PURPOSE: The adoption of electronic medical records (EMR) is expected to better
      improve overall healthcare quality and to offset the financial pressure of
      excessive administrative burden. However, safeguarding EMR against potentially
      hostile security breaches from both inside and outside healthcare facilities has
      created increased patients' privacy concerns from all sides. The aim of our study
      was to examine the influencing factors of privacy protection for EMR by
      healthcare professionals. METHOD: We used survey methodology to collect
      questionnaire responses from staff members in health information management
      departments among nine Taiwanese hospitals active in EMR utilisation. A total of
      209 valid responses were collected in 2014. We used partial least squares for
      analysing the collected data. RESULTS: Perceived benefits, perceived barriers,
      self-efficacy and cues to action were found to have a significant association
      with intention to protect EMR privacy, while perceived susceptibility and
      perceived severity were not. CONCLUSION: Based on the findings obtained, we
      suggest that hospitals should provide continuous ethics awareness training to
      relevant staff and design more effective strategies for improving the protection
      of EMR privacy in their charge. Further practical and research implications are
      also discussed.

PMID- 27702793
TI  - Candida tropicalis biofilm and human epithelium invasion is highly influenced by
      environmental pH.
AB  - OBJECTIVE: The main goal of this study was to investigate the role of pH on
      Candida tropicalis virulence determinants, namely the ability to form biofilms
      and to colonize/invade reconstituted human vaginal epithelia. METHODS: Biofilm
      formation was evaluated by enumeration of cultivable cells, total biomass
      quantification and structural analysis by scanning electron microscopy and
      confocal laser scanning microscopy. Candida tropicalis human vaginal epithelium
      colonization and invasiveness were examined qualitatively by epifluorescence
      microscopy and quantitatively by a novel quantitative real-time PCR protocol for
      Candida quantification in tissues. RESULTS: The results revealed that
      environmental pH influences C. tropicalis biofilm formation as well as the
      colonization and potential to invade human epithelium with intensification at
      neutral and alkaline conditions compared to acidic conditions. CONCLUSIONS: For
      the first time, we have demonstrated that C. tropicalis biofilm formation and
      invasion is highly influenced by environmental pH.

PMID- 27702794
TI  - Editorial: Infection and immunity research at the University of Maryland,
      Baltimore.

PMID- 27702796
TI  - Safety of extending screening intervals beyond five years in cervical screening
      programmes with testing for high risk human papillomavirus: 14 year follow-up of
      population based randomised cohort in the Netherlands.
AB  - OBJECTIVES:  To provide an early risk assessment of extending screening intervals
      beyond five years for a human papillomavirus (HPV) based cervical screening
      programme in the Netherlands. DESIGN:  14 year follow-up of a population based
      randomised cohort from the POBASCAM randomised trial. SETTING:  Organised
      cervical screening in the Netherlands, based on a programme of three screening
      rounds (each round done every five years). PARTICIPANTS:  43 339 women aged 29-61
      years with a negative HPV and/or negative cytology test participating in the
      POBASCAM trial. INTERVENTIONS:  Women randomly assigned to HPV and cytology co
      testing (intervention) or cytology testing only (control), and managed
      accordingly. MAIN OUTCOME MEASURES:  Cumulative incidence of cervical cancer and
      cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+). Associations
      with age were expressed as incidence rate ratios. In HPV positive women,
      reductions in CIN3+ incidence after negative cytology, HPV type 16/18 genotyping,
      and/or repeat cytology were estimated. RESULTS:  The cumulative incidence of
      cervical cancer (0.09%) and CIN3+ (0.56%) among HPV negative women in the
      intervention group after three rounds of screening were similar to the cumulative
      among women with negative cytology in the control group after two rounds (0.09%
      and 0.69%, respectively). Cervical cancer and CIN3+ risk ratios were 0.97 (95%
      confidence interval 0.41 to 2.31, P=0.95) and 0.82 (0.62 to 1.09, P=0.17),
      respectively. CIN3+ incidence was 72.2% (95% confidence interval 61.6% to 79.9%,
      P<0.001) lower among HPV negative women aged at least 40 years than among younger
      women. No significant association between cervical cancer incidence and age could
      be demonstrated. CIN3+ incidence among HPV positive women with negative cytology,
      HPV 16/18 genotyping, and/or repeat cytology was 10.4 (95% confidence interval
      5.9 to 18.4) times higher than among HPV negative women. CONCLUSIONS:  Long term
      incidences of cervical cancer and CIN3+ were low among HPV negative women in this
      study cohort, and supports an extension of the cervical screening interval beyond
      five years for women aged 40 years and older. HPV positive women with subsequent
      negative cytology, HPV16/18 genotyping, and/or repeat cytology have at least a
      fivefold higher risk of CIN3+ than HPV negative women, indicating that HPV based
      programmes with long intervals (>five years) should be implemented with risk
      stratification.Trial registration POBASCAM trial number ISRCTN20781131.

PMID- 27702795
TI  - Prevention of polymicrobial biofilms composed of Pseudomonas aeruginosa and
      pathogenic fungi by essential oils from selected Citrus species.
AB  - Mixed microbial infections caused by Pseudomonas aeruginosa and pathogenic fungi
      are commonly found in patients with chronic infections and constitute a
      significant health care burden. The aim of this study was to address the
      potential polymicrobial antibiofilm activity of pompia and grapefruit essential
      oils (EOs). The mechanism of antimicrobial activity of EOs was analysed. EOs of
      pompia and grapefruit inhibited fungal growth with MIC concentrations between 50
      and 250 mg L-1, whereas no effect on P. aeruginosa growth was observed. Both
      citrus EOs inhibited formation of bacterial and fungal monomicrobial biofilms in
      concentrations of 50 mg L-1 and were efficient in potentiating the activity of
      clinically used antimicrobials in vitro The concentration of 10 mg L-1 EOs
      inhibited mixed biofilm formation composed of P. aeruginosa and Aspergillus
      fumigatus or Scedosporium apiospermum Citrus EOs affected quorum sensing in P.
      aeruginosa and caused fast permeabilisation of Candida albicans membrane. Pompia
      and grapefruit EOs potently inhibited biofilm formation and could be used for the
      control of common polymicrobial infections.

PMID- 27702797
TI  - Case series of octogenarians with sickle cell disease.

PMID- 27702800
TI  - Excellent T-cell reconstitution and survival depend on low ATG exposure after
      pediatric cord blood transplantation.
AB  - Successful immune reconstitution (IR) is associated with improved outcomes
      following pediatric cord blood transplantation (CBT). Usage and timing of anti
      thymocyte globulin (ATG), introduced to the conditioning to prevent graft-versus
      host disease and graft failure, negatively influences T-cell IR. We studied the
      relationships among ATG exposure, IR, and clinical outcomes. All pediatric
      patients receiving a first CBT between 2004 and 2015 at the University Medical
      Center Utrecht were included. ATG-exposure measures were determined with a
      validated pharmacokinetics model. Main outcome of interest was early CD4+ IR,
      defined as CD4+ T-cell counts >50 * 106/L twice within 100 days after CBT. Other
      outcomes of interest included event-free survival (EFS). Cox proportional-hazard
      and Fine-Gray competing-risk models were used. A total of 137 patients, with a
      median age of 7.4 years (range, 0.2-22.7), were included, of whom 82% received
      ATG. Area under the curve (AUC) of ATG after infusion of the cord blood
      transplant predicted successful CD4+ IR. Adjusted probability on CD4+ IR was
      reduced by 26% for every 10-point increase in AUC after CBT (hazard ratio [HR],
      0.974; P < .0001). The chance of EFS was higher in patients with successful CD4+
      IR (HR, 0.26; P < .0001) and lower ATG exposure after CBT (HR, 1.005; P = .0071).
      This study stresses the importance of early CD4+ IR after CBT, which can be
      achieved by reducing the exposure to ATG after CBT. Individualized dosing of ATG
      to reach optimal exposure or, in selected patients, omission of ATG may
      contribute to improved outcomes in pediatric CBT.

PMID- 27702798
TI  - miR-125b controls monocyte adaptation to inflammation through mitochondrial
      metabolism and dynamics.
AB  - Metabolic changes drive monocyte differentiation and fate. Although abnormal
      mitochondria metabolism and innate immune responses participate in the
      pathogenesis of many inflammatory disorders, molecular events regulating
      mitochondrial activity to control life and death in monocytes remain poorly
      understood. We show here that, in human monocytes, microRNA-125b (miR-125b)
      attenuates the mitochondrial respiration through the silencing of the BH3-only
      proapoptotic protein BIK and promotes the elongation of the mitochondrial network
      through the targeting of the mitochondrial fission process 1 protein MTP18,
      leading to apoptosis. Proinflammatory activation of monocyte-derived macrophages
      is associated with a concomitant increase in miR-125b expression and decrease in
      BIK and MTP18 expression, which lead to reduced oxidative phosphorylation and
      enhanced mitochondrial fusion. In a chronic inflammatory systemic disorder, CD14+
      blood monocytes display reduced miR-125b expression as compared with healthy
      controls, inversely correlated with BIK and MTP18 messenger RNA expression. Our
      findings not only identify BIK and MTP18 as novel targets for miR-125b that
      control mitochondrial metabolism and dynamics, respectively, but also reveal a
      novel function for miR-125b in regulating metabolic adaptation of monocytes to
      inflammation. Together, these data unravel new molecular mechanisms for a
      proapoptotic role of miR-125b in monocytes and identify potential targets for
      interfering with excessive inflammatory activation of monocytes in inflammatory
      disorders.

PMID- 27702802
TI  - Dynamic disulfide/thiol homeostasis in lead exposure denoted by a novel method.
AB  - Lead is a toxic heavy metal, and prevention of human exposure to lead has not
      been accomplished yet. The toxicity of lead is continually being investigated,
      and the molecular mechanisms of its toxicity are still being revealed. In this
      study, we used a novel method to examine thiol (SH)/disulfide homeostasis in
      workers who were occupationally exposed to lead. A total of 80 such workers and
      70 control subjects were evaluated, and their native and total SH values were
      measured in serum using a novel method; their blood lead levels were also
      assessed. The novel method used for SH measurements was based on the principle of
      measuring native SH, after which disulfide bonds were reduced and total SHs were
      measured. These measurements allowed us to calculate disulfide amounts,
      disulfide/total SH percent ratios, disulfide/native SH percent ratios, and native
      SH /total SH percent ratios. We found that disulfide levels were significantly
      higher in workers who were exposed to lead (21.08(11.1-53.6) vs. 17.9(1.7-25), p
      < 0.001). Additionally, the disulfide/native SH and disulfide/total SH percent
      ratios were higher in exposed workers, while the native SH/total SH percent
      ratios were higher in the control subjects. Furthermore, the lead and disulfide
      levels showed a positive correlation, with p < 0.001 and a correlation
      coefficient of 0.378. Finally, the novel method used in this study successfully
      showed a switch from SH to disulfide after lead exposure, and the method is fully
      automated, easy, cheap, reliable, and reproducible. Use of this method in future
      cases may provide valuable insights into the management of lead exposure.

PMID- 27702799
TI  - Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple
      myeloma not refractory to bortezomib.
AB  - Proteasome inhibitors have become an integral part of myeloma therapy.
      Considerable efforts have gone into optimizing this therapeutic approach to
      obtain maximal proteasome inhibition with least toxicity. Ixazomib is the first
      oral proteasome inhibitor to enter the clinic and has been studied as a single
      agent as well as in various combinations. The current trial was designed to
      examine the efficacy and toxicity of combining 2 different doses of ixazomib (4
      mg and 5.5 mg given weekly for 3 of 4 weeks) with 40 mg weekly of dexamethasone,
      in relapsed myeloma. Seventy patients were enrolled, 35 patients randomly
      assigned to each ixazomib dose. Overall, 30 (43%; 95% confidence interval, 31-55)
      of the patients achieved a confirmed partial response or better, with 31%
      achieving a response with 4 mg and 54% with 5.5 mg of ixazomib. The median event
      free survival (EFS) for the entire study population was 8.4 months; 1-year
      overall survival was 96%. The EFS was 5.7 months for patients with prior
      bortezomib exposure and 11.0 months for bortezomib-naive patients. A grade 3 or 4
      adverse event considered at least possibly related to treatment was seen in 11
      (32%) patients at 4 mg and in 21 (60%) at 5.5 mg. Dose reductions were more
      frequent with 5.5 mg dose. Overall, the ixazomib with dexamethasone has good
      efficacy in relapsed myeloma, is well-tolerated and with higher response rate at
      5.5 mg, albeit with more toxicity. This study was registered at
      www.clinicaltrials.gov as #NCT01415882.

PMID- 27702801
TI  - LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores
      cholesterol efflux and triggers apoptosis.
AB  - Blastic plasmacytoid dendritic cell (PDC) neoplasm (BPDCN) is an aggressive
      hematological malignancy with a poor prognosis that derives from PDCs. No
      consensus for optimal treatment modalities is available today and the full
      characterization of this leukemia is still emerging. We identified here a BPDCN
      specific transcriptomic profile when compared with those of acute myeloid
      leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic
      signature of primary PDCs. This BPDCN gene signature identified a dysregulation
      of genes involved in cholesterol homeostasis, some of them being liver X receptor
      (LXR) target genes. LXR agonist treatment of primary BPDCN cells and BPDCN cell
      lines restored LXR target gene expression and increased cholesterol efflux via
      the upregulation of adenosine triphosphate-binding cassette (ABC) transporters,
      ABCA1 and ABCG1. LXR agonist treatment was responsible for limiting BPDCN cell
      proliferation and inducing intrinsic apoptotic cell death. LXR activation in
      BPDCN cells was shown to interfere with 3 signaling pathways associated with
      leukemic cell survival, namely: NF-kappaB activation, as well as Akt and STAT5
      phosphorylation in response to the BPDCN growth/survival factor interleukin-3.
      These effects were increased by the stimulation of cholesterol efflux through a
      lipid acceptor, the apolipoprotein A1. In vivo experiments using a mouse model of
      BPDCN cell xenograft revealed a decrease of leukemic cell infiltration and BPDCN
      induced cytopenia associated with increased survival after LXR agonist treatment.
      This demonstrates that cholesterol homeostasis is modified in BPDCN and can be
      normalized by treatment with LXR agonists which can be proposed as a new
      therapeutic approach.

PMID- 27702803
TI  - Is an Oral Anticoagulant Necessary for Young Atrial Fibrillation Patients With a
      CHA2DS2-VASc Score of 1 (Men) or 2 (Women)?
AB  - BACKGROUND: Recent studies demonstrated that oral anticoagulants (OACs) should be
      considered for patients with atrial fibrillation and 1 risk factor in addition to
      sex. Because age is an important determinant of ischemic stroke, the strategy for
      stroke prevention may be different for these patients in different age strata.
      The aim of this study was to investigate whether OACs should be considered for
      patients aged 20 to 49 years with atrial fibrillation and a CHA2DS2-VASc score of
      1 (men) or 2 (women). METHODS AND RESULTS: Using the Taiwan National Health
      Insurance Research Database, 7374 male patients with atrial fibrillation and a
      CHA2DS2-VASc score of 1 and 4461 female patients with atrial fibrillation and a
      CHA2DS2-VASc score of 2 and all without antithrombotic therapies were identified
      and stratified into 3 groups by age. The threshold for the initiation of OACs for
      stroke prevention was set at a stroke rate of 1.7% per year for warfarin and 0.9%
      per year for non-vitamin K antagonist OACs. Among male patients aged 20 to 49
      years with a CHA2DS2-VASc score of 1, the risk of ischemic stroke was 1.30% per
      year and ranged from 0.94% per year for those with hypertension to 1.71% for
      those with congestive heart failure. Among female patients aged 20 to 49 years
      with a CHA2DS2-VASc score of 2, the risk of ischemic stroke was 1.40% per year
      and ranged from 1.11% per year for those with hypertension to 1.67% for those
      with congestive heart failure. CONCLUSIONS: For atrial fibrillation patients aged
      20 to 49 years with 1 risk factor in addition to sex, non-vitamin K antagonist
      OACs should be considered for stroke prevention to minimize the risk of a
      potentially fatal or disabling event.

PMID- 27702804
TI  - Hemodynamic Tandem Intracranial Lesions on Magnetic Resonance Angiography in
      Patients Undergoing Carotid Endarterectomy.
AB  - BACKGROUND: Hemodynamic tandem intracranial lesions (TILs) on intracranial
      magnetic resonance angiography, which develop flow dependently, have been
      overlooked clinically in patients undergoing carotid endarterectomy. As they
      represent severe baseline hemodynamic compromise at the segment, they may be
      associated with distinctive clinical outcomes. METHODS AND RESULTS: We assessed
      304 consecutive carotid endarterectomy cases treated over 3 years. Included cases
      had both preoperative and postoperative intracranial 3-dimensional time-of-flight
      magnetic resonance angiography, of which signal intensities are flow dependent,
      and postoperative diffusion-weighted imaging (<=3 days following carotid
      endarterectomy). Preoperative TILs in the ipsilateral intracranial arteries were
      evaluated by the presence of nonexclusive components: focal stenosis (>50%),
      diffuse stenosis (>50%), and decreased signal intensities (>50%). The components
      showing postoperative normalization were considered hemodynamic. TILs with
      hemodynamic components were defined as hemodynamic TILs, while others as
      consistent TILs. Baseline characteristics and postoperative outcomes were
      analyzed among 3 groups: no TILs, consistent TILs, and hemodynamic TILs.
      Preoperative TILs were identified in 104 (34.2%) cases; 54 (17.8%) had
      hemodynamic components. Diffuse stenosis and decreased signal intensities were
      usually reversed postoperatively. Patients with hemodynamic TILs tended to have
      severe proximal carotid stenosis and recent strokes (<=14 days). For the outcome,
      hemodynamic TILs were independently associated with the advent of postoperative
      ischemic lesions on diffusion-weighted imaging (odds ratio: 2.50; 95% CI, 1.20
      5.20). CONCLUSIONS: In patients undergoing carotid endarterectomy, a significant
      number of preoperative TILs demonstrated hemodynamic components, which were
      reversed postoperatively. The presence of such components was distinctively
      associated with the postoperative incidence of new ischemic lesions.

PMID- 27702806
TI  - Changes in white spot lesions following post-orthodontic weekly application of
      1.25 per cent fluoride gel over 6 months-a randomized placebo-controlled clinical
      trial. Part I: photographic data evaluation.
AB  - Background: White spot lesions (WSLs) are a frequent side-effect of multibracket
      appliance treatment. The effect of local fluoridation on post-orthodontic WSL is
      however inconclusive. Objective: Assessment of WSL changes in response to weekly
      1.25 per cent fluoride gel application after multibracket appliance treatment.
      Trial design: Randomized, single-centre, double-blind, parallel-group, placebo
      controlled study. Participants: Patients with not less than 1 WSL (modified score
      1 or 2) on not less than 1 upper front teeth after debonding. Interventions:
      Professional fluoride/placebo gel application during weeks 1-2; self-administered
      home application (weeks 3-24). Outcomes: Photographic WSL assessment (dimension
      and luminance) of the upper front teeth (T0-T5). Randomization: Random assignment
      to test (n = 23) or placebo group (n = 23) using a sequentially numbered list
      (random allocation sequence generated for 50 subjects in 25 blocks of 2 subjects
      each). Recruitment: The clinical study duration lasted from March 2011 to
      September 2013. Blinding: Unblinding was performed after complete data
      evaluation. Numbers analysed: Intent-to-treat analysis set comprising 39
      participants (test: n = 21, placebo: n = 18). Outcome: Dimensional WSL
      quantification showed limited reliability. Luminance improvement (%) of WSL,
      however, was seen after 6 months (test/placebo: tooth 12, 24.8/18.0; tooth 11,
      38.4/35.4; tooth 21, 39.6/38.3; and tooth 22, 15.2/25.0). No statistically
      significant group difference existed. Data suggest that WSLs are difficult to
      measure with respect to reliability and repeatability and methods for monitoring
      WSLs in clinical trials require improvement/validation. Harms: Similar adverse
      events occurred in both groups; none was classified as possibly related to the
      study product. Limitations: The number of dropouts was higher than expected and
      the socio-economic status was not assessed. Furthermore, the unknown level of
      compliance during the home application phase must be considered as limitation.
      Conclusion: Based on the results of this study, no difference could be detected
      with respect to the development of WSL under post-orthodontic high-dose fluoride
      treatment. Registration: The study was registered with ClinicalTrials.gov
      (Identifier: NCT01329731). Protocol: The protocol wasn't published before trial
      commencement.

PMID- 27702805
TI  - A Pilot Randomized Controlled Trial of the Feasibility, Acceptability, and Impact
      of Giving Information on Personalized Genomic Risk of Melanoma to the Public.
AB  - BACKGROUND: Communication of personalized melanoma genomic risk information may
      improve melanoma prevention behaviors. METHODS: We evaluated the feasibility and
      acceptability of communicating personalized genomic risk of melanoma to the
      public and its preliminary impact on behaviors and psychosocial outcomes. One
      hundred eighteen people aged 22 to 69 years provided a saliva sample and were
      randomized to the control (nonpersonalized educational materials) or intervention
      (personalized booklet presenting melanoma genomic risk as absolute and relative
      risks and a risk category based on variants in 21 genes, telephone-based genetic
      counseling, and nonpersonalized educational materials). Intention-to-treat
      analyses overall and by-risk category were conducted using ANCOVA adjusted for
      baseline values. RESULTS: Consent to participate was 41%, 99% were successfully
      genotyped, and 92% completed 3-month follow-up. Intervention participants
      reported high satisfaction with the personalized booklet (mean = 8.6, SD = 1.6;
      on a 0-10 scale) and genetic counseling (mean = 8.1, SD = 2.2). No significant
      behavioral effects at 3-month follow-up were identified between intervention and
      control groups overall: objectively measured standard erythemal doses per day [
      16%; 95% confidence interval (CI), -43% to 24%] and sun protection index (0.05;
      95% CI, -0.07 to 0.18). There was increased confidence identifying melanoma at 3
      months (0.40; 95% CI, 0.10-0.69). Stratified by risk category, effect sizes for
      intentional tanning and some individual sun protection items appeared stronger
      for the average-risk group. There were no appreciable group differences in skin
      cancer-related worry or psychologic distress. CONCLUSIONS: Our results
      demonstrate feasibility and acceptability of providing personalized genomic risk
      of melanoma to the public. IMPACT: Genomic risk information has potential as a
      melanoma prevention strategy. Cancer Epidemiol Biomarkers Prev; 26(2); 212-21.
      (c)2016 AACR.

PMID- 27702807
TI  - Changes in white spot lesions following post-orthodontic weekly application of
      1.25 per cent fluoride gel over 6 months-a randomized placebo-controlled clinical
      trial. Part II: clinical data evaluation.
AB  - Background: White spot lesions (WSL) frequently occur as side-effect of
      multibracket appliance treatment. The clinical effects of local fluoridation on
      post-orthodontic WSL and oral health development are however inconclusive.
      Objective: In vivo monitoring of clinical WSL and oral health changes in response
      to weekly 1.25 per cent fluoride gel application after multibracket appliance
      treatment. Trial design: Randomized, single-centre, double-blind, parallel-group,
      placebo-controlled study. Participants: Patients with not less than 1 WSL
      (modified score 1 or 2) on not less than 1 upper front teeth after debonding.
      Interventions: Professional fluoride/placebo gel application during weeks 1-2;
      self-administered home application (weeks 3-24). Outcomes: Clinical evaluation of
      WSL index, lesion activity, plaque index, gingival bleeding index, and decayed,
      missing, and filled teeth index as well as saliva buffer capacity and stimulated
      salivary flow rate (T0-T5). Randomization: Random assignment to test (n = 23) or
      placebo group (n = 23) using a sequentially numbered list (random allocation
      sequence generated for 50 subjects in 25 blocks of 2 subjects each). Recruitment:
      The clinical study duration lasted from March 2011 to September 2013. Blinding:
      Unblinding was performed after complete data evaluation. Numbers analysed:
      Intention-to-treat analysis set comprised 39 participants (test: n = 21, placebo:
      n = 18). Outcome: No clinical parameter except stimulated salivary flow rate
      (fluoride group: 1.1ml/min, placebo group: 0.74ml/min; P = 0.022) showed a
      statistically significant group difference after 24 weeks. Harms: Several adverse
      events occurred similarly frequent in both groups; none was classified as
      possibly related to the study product. Limitations: The number of dropouts was
      higher than expected and the socio-economic status was not assessed. Furthermore,
      the unknown level of compliance during the home application phase must be
      considered as limitation. Conclusion: Based on the results of this study, no
      clinical effect of post-orthodontic high-dose fluoride treatment on WSL and oral
      health changes could be detected. Registration: The study was registered with
      ClinicalTrials.gov (Identifier: NCT01329731). Protocol: The protocol wasn't
      published before trial commencement.

PMID- 27702810
TI  - Altered Global Signal Topography in Schizophrenia.
AB  - Schizophrenia (SCZ) is a disabling neuropsychiatric disease associated with
      disruptions across distributed neural systems. Resting-state functional magnetic
      resonance imaging has identified extensive abnormalities in the blood-oxygen
      level-dependent signal in SCZ patients, including alterations in the average
      signal over the brain-i.e. the "global" signal (GS). It remains unknown, however,
      if these "global" alterations occur pervasively or follow a spatially
      preferential pattern. This study presents the first network-by-network
      quantification of GS topography in healthy subjects and SCZ patients. We observed
      a nonuniform GS contribution in healthy comparison subjects, whereby sensory
      areas exhibited the largest GS component. In SCZ patients, we identified
      preferential GS representation increases across association regions, while
      sensory regions showed preferential reductions. GS representation in sensory
      versus association cortices was strongly anti-correlated in healthy subjects.
      This anti-correlated relationship was markedly reduced in SCZ. Such shifts in GS
      topography may underlie profound alterations in neural information flow in SCZ,
      informing development of pharmacotherapies.

PMID- 27702811
TI  - Within-Category Decoding of Information in Different Attentional States in Short
      Term Memory.
AB  - A long-standing assumption of cognitive neuroscience has been that working memory
      (WM) is accomplished by sustained, elevated neural activity. More recently,
      theories of WM have expanded this view by describing different attentional states
      in WM with differing activation levels. Several studies have used multivariate
      pattern analysis (MVPA) of functional magnetic resonance imaging (fMRI) and
      electroencephalography (EEG) data to study neural activity corresponding to these
      WM states. Intriguingly, no evidence was found for active neural representations
      for information held in WM outside the focus of attention ("unattended memory
      items," UMIs), suggesting that only attended memory items (AMIs) are accompanied
      by an active trace. However, these results depended on category-level decoding,
      which lacks sensitivity to neural representations of individual items. Therefore,
      we employed a WM task in which subjects remembered the directions of motion of
      two dot arrays, with a retrocue indicating which was relevant for an imminent
      memory probe (the AMI). This design allowed MVPA decoding of delay-period fMRI
      signal at the stimulus-item level, affording a more sensitive test of the neural
      representation of UMIs. Whereas evidence for the AMI was reliably high, evidence
      for the UMI dropped to baseline, consistent with the notion that different WM
      attentional states may have qualitatively different mechanisms of retention.

PMID- 27702812
TI  - An Electrophysiological Index of Perceptual Goodness.
AB  - A traditional line of work starting with the Gestalt school has shown that
      patterns vary in strength and salience; a difference in "Perceptual goodness."
      The Holographic weight of evidence model quantifies goodness of visual
      regularities. The key formula states that W = E/N, where E is number of
      holographic identities in a pattern and N is number of elements. We tested
      whether W predicts the amplitude of the neural response to regularity in an
      extrastriate symmetry-sensitive network. We recorded an Event Related Potential
      (ERP) generated by symmetry called the Sustained Posterior Negativity (SPN).
      First, we reanalyzed the published work and found that W explained most variance
      in SPN amplitude. Then in four new studies, we confirmed specific predictions of
      the holographic model regarding 1) the differential effects of numerosity on
      reflection and repetition, 2) the similarity between reflection and Glass
      patterns, 3) multiple symmetries, and 4) symmetry and anti-symmetry. In all
      cases, the holographic approach predicted SPN amplitude remarkably well;
      particularly in an early window around 300-400 ms post stimulus onset. Although
      the holographic model was not conceived as a model of neural processing, it
      captures many details of the brain response to symmetry.

PMID- 27702813
TI  - Maize Cytolines Unmask Key Nuclear Genes That Are under the Control of Retrograde
      Signaling Pathways in Plants.
AB  - The genomes of the two plant organelles encode for a relatively small number of
      proteins. Thus, nuclear genes encode the vast majority of their proteome.
      Organelle-to-nucleus communication takes place through retrograde signaling (RS)
      pathways. Signals relayed through RS pathways have an impact on nuclear gene
      expression but their target-genes remain elusive in a normal state of the cell
      (considering that only mutants and stress have been used so far). Here, we use
      maize cytolines as an alternative. The nucleus of a donor line was transferred
      into two other cytoplasmic environments through at least nine back-crosses, in a
      time-span of > 10 years. The transcriptomes of the resulting cytolines were
      sequenced and compared. There are 96 differentially regulated nuclear genes in
      two cytoplasm-donor lines when compared with their nucleus-donor. They are
      expressed throughout plant development, in various tissues and organs. One-third
      of the 96 proteins have a human homolog, stressing their potential role in
      mitochondrial RS. We also identified syntenic orthologous genes in four other
      grasses and homologous genes in Arabidopsis thaliana These findings contribute to
      the paradigm we use to describe the RS in plants. The 96 nuclear genes identified
      here are not differentially regulated as a result of mutation, or any kind of
      stress. They are rather key players of the organelle-to-nucleus communication in
      a normal state of the cell.

PMID- 27702814
TI  - LINEs between Species: Evolutionary Dynamics of LINE-1 Retrotransposons across
      the Eukaryotic Tree of Life.
AB  - LINE-1 (L1) retrotransposons are dynamic elements. They have the potential to
      cause great genomic change because of their ability to 'jump' around the genome
      and amplify themselves, resulting in the duplication and rearrangement of
      regulatory DNA. Active L1, in particular, are often thought of as tightly
      constrained, homologous and ubiquitous elements with well-characterized domain
      organization. For the past 30 years, model organisms have been used to define L1s
      as 6-8 kb sequences containing a 5'-UTR, two open reading frames working
      harmoniously in cis, and a 3'-UTR with a polyA tail. In this study, we
      demonstrate the remarkable and overlooked diversity of L1s via a comprehensive
      phylogenetic analysis of elements from over 500 species from widely divergent
      branches of the tree of life. The rapid and recent growth of L1 elements in
      mammalian species is juxtaposed against the diverse lineages found in other
      metazoans and plants. In fact, some of these previously unexplored mammalian
      species (e.g. snub-nosed monkey, minke whale) exhibit L1 retrotranspositional
      'hyperactivity' far surpassing that of human or mouse. In contrast, non-mammalian
      L1s have become so varied that the current classification system seems to
      inadequately capture their structural characteristics. Our findings illustrate
      how both long-term inherited evolutionary patterns and random bursts of activity
      in individual species can significantly alter genomes, highlighting the
      importance of L1 dynamics in eukaryotes.

PMID- 27702815
TI  - Selective Landscapes in newt Immune Genes Inferred from Patterns of Nucleotide
      Variation.
AB  - Host-pathogen interactions may result in either directional selection or in
      pressure for the maintenance of polymorphism at the molecular level. Hence
      signatures of both positive and balancing selection are expected in immune genes.
      Because both overall selective pressure and specific targets may differ between
      species, large-scale population genomic studies are useful in detecting
      functionally important immune genes and comparing selective landscapes between
      taxa. Such studies are of particular interest in amphibians, a group threatened
      worldwide by emerging infectious diseases. Here, we present an analysis of
      polymorphism and divergence of 634 immune genes in two lineages of Lissotriton
      newts: L. montandoni and L. vulgaris graecus Variation in newt immune genes has
      been shaped predominantly by widespread purifying selection and strong
      evolutionary constraint, implying long-term importance of these genes for
      functioning of the immune system. The two evolutionary lineages differ in the
      overall strength of purifying selection which can partially be explained by
      demographic history but may also signal differences in long-term pathogen
      pressure. The prevalent constraint notwithstanding, 23 putative targets of
      positive selection and 11 putative targets of balancing selection were
      identified. The latter were detected by composite tests involving the demographic
      model and further validated in independent population samples. Putative targets
      of balancing selection encode proteins which may interact closely with pathogens
      but include also regulators of immune response. The identified candidates will be
      useful for testing whether genes affected by balancing selection are more prone
      to interspecific introgression than other genes in the genome.

PMID- 27702816
TI  - Variable Autosomal and X Divergence Near and Far from Genes Affects Estimates of
      Male Mutation Bias in Great Apes.
AB  - Male mutation bias, when more mutations are passed on via the male germline than
      via the female germline, is observed across mammals. One common way to infer the
      magnitude of male mutation bias, alpha, is to compare levels of neutral sequence
      divergence between genomic regions that spend different amounts of time in the
      male and female germline. For great apes, including human, we show that estimates
      of divergence are reduced in putatively unconstrained regions near genes relative
      to unconstrained regions far from genes. Divergence increases with increasing
      distance from genes on both the X chromosome and autosomes, but increases faster
      on the X chromosome than autosomes. As a result, ratios of X/A divergence
      increase with increasing distance from genes and corresponding estimates of male
      mutation bias are significantly higher in intergenic regions near genes versus
      far from genes. Future studies in other species will need to carefully consider
      the effect that genomic location will have on estimates of male mutation bias.

PMID- 27702817
TI  - Ovarian Cancers Harbor Defects in Nonhomologous End Joining Resulting in
      Resistance to Rucaparib.
AB  - Purpose: DNA damage defects are common in ovarian cancer and can be used to
      stratify treatment. Although most work has focused on homologous recombination
      (HR), DNA double-strand breaks are repaired primarily by nonhomologous end
      joining (NHEJ). Defects in NHEJ have been shown to contribute to genomic
      instability and have been associated with the development of
      chemoresistance.Experimental Design: NHEJ was assessed in a panel of ovarian
      cancer cell lines and 47 primary ascetic-derived ovarian cancer cultures, by
      measuring the ability of cell extracts to end-join linearized plasmid monomers
      into multimers. mRNA and protein expression of components of NHEJ was determined
      using RT-qPCR and Western blotting. Cytotoxicities of cisplatin and the PARP
      inhibitor rucaparib were assessed using sulforhodamine B (SRB) assays. HR
      function was assessed using gammaH2AX/RAD51 foci assay.Results: NHEJ was
      defective (D) in four of six cell lines and 20 of 47 primary cultures. NHEJ
      function was independent of HR competence (C). NHEJD cultures were resistant to
      rucaparib (P = 0.0022). When HR and NHEJ functions were taken into account, only
      NHEJC/HRD cultures were sensitive to rucaparib (compared with NHEJC/HRC P =
      0.034, NHEJD/HRC P = 0.0002, and NHEJD/HRD P = 0.0045). The DNA-PK inhibitor,
      NU7441, induced resistance to rucaparib (P = 0.014) and HR function recovery in a
      BRCA1-defective cell line.Conclusions: This study has shown that NHEJ is
      defective in 40% of ovarian cancers, which is independent of HR function and
      associated with resistance to PARP inhibitors in ex vivo primary cultures. Clin
      Cancer Res; 23(8); 2050-60. (c)2016 AACR.

PMID- 27702818
TI  - Paired High-Content Analysis of Prostate Cancer Cells in Bone Marrow and Blood
      Characterizes Increased Androgen Receptor Expression in Tumor Cell Clusters.
AB  - Purpose: Recent studies demonstrate that prostate cancer clones from different
      metastatic sites are dynamically represented in the blood of patients over time,
      suggesting that the paired evaluation of tumor cells in circulation and bone
      marrow, the primary target for prostate cancer metastasis, may provide
      complementary information.Experimental Design: We adapted our single-cell high
      content liquid biopsy platform to bone marrow aspirates (BMA) to concurrently
      identify and characterize prostate cancer cells in patients' blood and bone and
      thus discern features associated to tumorigenicity and dynamics of metastatic
      progression.Results: The incidence of tumor cells in BMAs increased as the
      disease advanced: 0% in biochemically recurrent (n = 52), 26% in newly diagnosed
      metastatic hormone-naive (n = 26), and 39% in metastatic castration-resistant
      prostate cancer (mCRPC; n = 63) patients, and their number was often higher than
      in paired blood. Tumor cell detection in metastatic patients' BMAs was concordant
      but 45% more sensitive than using traditional histopathologic interpretation of
      core bone marrow biopsies. Tumor cell clusters were more prevalent and bigger in
      BMAs than in blood, expressed higher levels of the androgen receptor protein per
      tumor cell, and were prognostic in mCRPC. Moreover, the patterns of genomic copy
      number variation in single tumor cells in paired blood and BMAs showed
      significant inter- and intrapatient heterogeneity.Conclusions: Paired analysis of
      single prostate cancer cells in blood and bone shows promise for clinical
      application and provides complementary information. The high prevalence and
      prognostic significance of tumor cell clusters, particularly in BMAs, suggest
      that these structures are key mediators of prostate cancer's metastatic
      progression. Clin Cancer Res; 23(7); 1722-32. (c)2016 AACR.

PMID- 27702819
TI  - Molecular Pathways: Dietary Regulation of Stemness and Tumor Initiation by the
      PPAR-delta Pathway.
AB  - Peroxisome proliferator-activated receptor delta (PPAR-delta) is a nuclear
      receptor transcription factor that regulates gene expression during development
      and disease states, such as cancer. However, the precise role of PPAR-delta
      during tumorigenesis is not well understood. Recent data suggest that PPAR-delta
      may have context-specific oncogenic and tumor-suppressive roles depending on the
      tissue, cell-type, or diet-induced physiology in question. For example, in the
      intestine, pro-obesity diets, such as a high-fat diet (HFD), are associated with
      increased colorectal cancer incidence. Interestingly, many of the effects of an
      HFD in the stem and progenitor cell compartment are driven by a robust PPAR-delta
      program and contribute to the early steps of intestinal tumorigenesis.
      Importantly, the PPAR-delta pathway or its downstream mediators may serve as
      therapeutic intervention points or biomarkers in colon cancer that arise in
      patients who are obese. Although potent PPAR-delta agonists and antagonists
      exist, their clinical utility may be enhanced by uncovering how PPAR-delta
      mediates tumorigenesis in diverse tissues and cell types as well as in response
      to diet. Clin Cancer Res; 22(23); 5636-41. (c)2016 AACR.

PMID- 27702820
TI  - Fibroblast Subtypes Regulate Responsiveness of Luminal Breast Cancer to Estrogen.
AB  - Purpose: Antiendocrine therapy remains the most effective treatment for estrogen
      receptor-positive (ER+) breast cancer, but development of resistance is a major
      clinical complication. Effective targeting of mechanisms that control the loss of
      ER dependency in breast cancer remains elusive. We analyzed breast cancer
      associated fibroblasts (CAF), the largest component of the tumor
      microenvironment, as a factor contributing to ER expression levels and
      antiendocrine resistance.Experimental Design: Tissues from patients with ER+
      breast cancer were analyzed for the presence of CD146-positive (CD146pos) and
      CD146-negative (CD146neg) fibroblasts. ER-dependent proliferation and tamoxifen
      sensitivity were evaluated in ER+ tumor cells cocultured with CD146pos or
      CD146neg fibroblasts. RNA sequencing was used to develop a high-confidence gene
      signature that predicts for disease recurrence in tamoxifen-treated patients with
      ER+ breast cancer.Results: We demonstrate that ER+ breast cancers contain two CAF
      subtypes defined by CD146 expression. CD146neg CAFs suppress ER expression in ER+
      breast cancer cells, decrease tumor cell sensitivity to estrogen, and increase
      tumor cell resistance to tamoxifen therapy. Conversely, the presence of CD146pos
      CAFs maintains ER expression in ER+ breast cancer cells and sustains estrogen
      dependent proliferation and sensitivity to tamoxifen. Conditioned media from
      CD146pos CAFs with tamoxifen-resistant breast cancer cells are sufficient to
      restore tamoxifen sensitivity. Gene expression profiles of patient breast tumors
      with predominantly CD146neg CAFs correlate with inferior clinical response to
      tamoxifen and worse patient outcomes.Conclusions: Our data suggest that CAF
      composition contributes to treatment response and patient outcomes in ER+ breast
      cancer and should be considered a target for drug development. Clin Cancer Res;
      23(7); 1710-21. (c)2016 AACR.

PMID- 27702823
TI  - Effects of Budesonide on Cabazitaxel Pharmacokinetics and Cabazitaxel-Induced
      Diarrhea: A Randomized, Open-Label Multicenter Phase II Study.
AB  - Purpose: Forty-seven percent of patients in the pivotal trial of cabazitaxel
      reported diarrhea of any grade. Aiming to reduce the incidence of diarrhea, we
      studied the effects of budesonide on the grade of cabazitaxel-induced diarrhea
      during the first two treatment cycles.Experimental Design: Between December 2011
      and October 2015, 246 metastatic castration-resistant prostate cancer patients
      were randomized to receive standard-of-care cabazitaxel 25 mg/m2 every 3 weeks
      plus prednisone 10 mg/day (group CABA) or same dose/schedule of cabazitaxel with
      concomitant budesonide 9 mg daily during the first two treatment cycles (group
      BUD). The occurrence of diarrhea was reported by physicians and by patients in a
      diary. chi2 tests were used to compare incidence numbers. An intention-to-treat
      principle was used.Results: In the phase II trial, 227 patients were evaluable.
      Grade 2-3 diarrhea occurred in 35 patients (15%) and grade 4 diarrhea was not
      reported. The incidence of grade 2-3 diarrhea was comparable in both treatment
      groups: 14 of 113 patients in group CABA (12%) versus 21 of 114 patients in group
      BUD (18%; P = 0.21). Seven patients were admitted to the hospital with diarrhea
      (n = 5 group CABA vs. n = 2 group BUD). PSA response was seen in 30% of patients
      and was not affected by budesonide coadministration (P = 0.29). Also, other
      toxicities were not affected by budesonide coadministration.Conclusions: The
      incidence of cabazitaxel-induced diarrhea was notably lower than reported in the
      TROPIC trial and appears manageable in routine clinical practice. Budesonide
      coadministration did not reduce the incidence or severity of cabazitaxel-induced
      diarrhea. Clin Cancer Res; 23(7); 1679-83. (c)2016 AACR.

PMID- 27702821
TI  - Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy.
AB  - Purpose: Immunotherapy is an emerging paradigm for the treatment of cancer, but
      the potential efficacy of many drugs cannot be sufficiently tested in the mouse.
      We sought to develop a rational combination of motolimod-a novel Toll-like
      receptor 8 (TLR8) agonist that stimulates robust innate immune responses in
      humans but diminished responses in mice-with pegylated liposomal doxorubicin
      (PLD), a chemotherapeutic that induces immunogenic cell death.Experimental
      Design: We followed an integrative pharmacologic approach including healthy human
      volunteers, non-human primates, NSG-HIS ("humanized immune system") mice
      reconstituted with human CD34+ cells, and patients with cancer to test the
      effects of motolimod and to assess the combination of motolimod with PLD for the
      treatment of ovarian cancer.Results: The pharmacodynamic effects of motolimod
      monotherapy in NSG-HIS mice closely mimicked those in non-human primates and
      healthy human subjects, whereas the effects of the motolimod/PLD combination in
      tumor-bearing NSG-HIS mice closely mimicked those in patients with ovarian cancer
      treated in a phase Ib trial (NCT01294293). The NSG-HIS mouse helped elucidate the
      mechanism of action of the combination and revealed a positive interaction
      between the two drugs in vivo The combination produced no dose-limiting
      toxicities in patients with ovarian cancer. Two subjects (15%) had complete
      responses and 7 subjects (53%) had disease stabilization. A phase II study was
      consequently initiated.Conclusions: These results are the first to demonstrate
      the value of pharmacologic approaches integrating the NSG-HIS mouse, non-human
      primates, and patients with cancer for the development of novel immunomodulatory
      anticancer agents with human specificity. Clin Cancer Res; 23(8); 1955-66.
      (c)2016 AACR.

PMID- 27702822
TI  - Constitutive IRAK4 Activation Underlies Poor Prognosis and Chemoresistance in
      Pancreatic Ductal Adenocarcinoma.
AB  - Purpose: Aberrant activation of the NF-kappaB transcription factors underlies the
      aggressive behavior and poor outcome of pancreatic ductal adenocarcinoma (PDAC).
      However, clinically effective and safe NF-kappaB inhibitors are not yet
      available. Because NF-kappaB transcription factors can be activated by the
      interleukin-1 receptor-associated kinases (IRAKs) downstream of the Toll-like
      receptors (TLRs), but has not been explored in PDAC, we sought to investigate the
      role of IRAKs in the pathobiology of PDAC.Experimental Design: We examined the
      phosphorylation status of IRAK4 (p-IRAK4), the master regulator of TLR signaling,
      in PDAC cell lines, in surgical samples and commercial tissue microarray. We then
      performed functional studies using small-molecule IRAK1/4 inhibitor, RNA
      interference, and CRISPR/Cas9n techniques to delineate the role of IRAK4 in NF
      kappaB activity, chemoresistance, cytokine production, and growth of PDAC cells
      in vitro and in vivoResults: p-IRAK4 staining was detectable in the majority of
      PDAC lines and about 60% of human PDAC samples. The presence of p-IRAK4 strongly
      correlated with phospho-NF-kappaB/p65 staining in PDAC samples and is predictive
      of postoperative relapse and poor overall survival. Inhibition of IRAK4 potently
      reduced NF-kappaB activity, anchorage-independent growth, chemoresistance, and
      secretion of proinflammatory cytokines from PDAC cells. Both pharmacologic
      suppression and genetic ablation of IRAK4 greatly abolished PDAC growth in mice
      and augmented the therapeutic effect of gemcitabine by promoting apoptosis,
      reducing tumor cell proliferation and tumor fibrosis.Conclusions: Our data
      established IRAK4 as a novel therapeutic target for PDAC treatment. Development
      of potent IRAK4 inhibitors is needed for clinical testing. Clin Cancer Res;
      23(7); 1748-59. (c)2016 AACR.

PMID- 27702825
TI  - Integrative Network-based Analysis of Colonic Detoxification Gene Expression in
      Ulcerative Colitis According to Smoking Status.
AB  - Backgrounds and Aims: The effect of cigarette smoking [CS] is ambivalent since
      smoking improves ulcerative colitis [UC] while it worsens Crohn's disease [CD].
      Although this clinical relationship between inflammatory bowel disease [IBD] and
      tobacco is well established, only a few experimental works have investigated the
      effect of smoking on the colonic barrier homeostasis focusing on xenobiotic
      detoxification genes. Methods: A comprehensive and integrated comparative
      analysis of the global xenobiotic detoxification capacity of the normal colonic
      mucosa of healthy smokers [n = 8] and non-smokers [n = 9] versus the non-affected
      colonic mucosa of UC patients [n = 19] was performed by quantitative real-time
      polymerase chain reaction [qRT PCR]. The detoxification gene expression profile
      was analysed in CD patients [n = 18], in smoking UC patients [n = 5], and in
      biopsies from non-smoking UC patients cultured or not with cigarette smoke
      extract [n = 8]. Results: Of the 244 detoxification genes investigated, 65 were
      dysregulated in UC patients in comparison with healthy controls or CD patients.
      The expression of >= 45/65 genes was inversed by CS in biopsies of smoking UC
      patients in remission and in colonic explants of UC patients exposed to cigarette
      smoke extract. We devised a network-based data analysis approach for
      differentially assessing changes in genetic interactions, allowing identification
      of unexpected regulatory detoxification genes that may play a major role in the
      beneficial effect of smoking on UC. Conclusions: Non-inflamed colonic mucosa in
      UC is characterised by a specifically altered detoxification gene network, which
      is partially restored by tobacco. These mucosal signatures could be useful for
      developing new therapeutic strategies and biomarkers of drug response in UC.

PMID- 27702828
TI  - Serious cardiac compression after ruptured thoraco-abdominal aortic aneurysm and
      endovascular repair.

PMID- 27702829
TI  - Single-stage, three-fold repair for Ebstein's anomaly.
AB  - Objectives: Favourable outcomes in the repair of Ebstein's anomaly are predicated
      on tricuspid valve competence, right ventricular function and presence of
      arrhythmia. We report our experience with a single-stage, three-fold repair of
      Ebstein's anomaly, namely, cone reconstruction of the tricuspid valve
      supplemented by bidirectional cavopulmonary anastomosis and right atrial
      electrocautery maze. Methods: From 2010 to 2014, 37 consecutive patients with
      Ebstein's anomaly, median age 17.3 (9.1-56.2) years, underwent this single-stage,
      three-fold surgical procedure. The principal elements of the procedure include
      (i) cone reconstruction of the tricuspid valve, limited plication at the level of
      the displaced valve, insertion of a homemade annuloplasty ring, defect repair and
      reduction atrioplasty supplemented by (ii) right atrial electrocautery maze and
      (iii) bidirectional cavopulmonary anastomosis. Postoperatively, all patients were
      followed up regularly for a mean period of 2.3 (1-4) years by clinical,
      electrocardiographic and echocardiographic examinations. Results: The in-hospital
      mortality rate was 2.7% (1 patient) with no late deaths. Mean cardiopulmonary
      bypass time was 110 +/- 18.3 min and aortic cross-clamp time was 48.5 +/- 7.4
      min. Echocardiographic examination showed significant improvement of valve
      regurgitation (P < 0.0001). NYHA functional class was I in 77.8% of the survivors
      and II in 22.2%. The cardiothoracic ratio decreased significantly (P < 0.05). No
      deleterious effects of the Glenn shunts have been reported. Sinus rhythm has
      remained stable in 31 patients (86.1%) during the follow-up period. Conclusions:
      Single-stage, three-fold repair for the management of Ebstein's anomaly offers
      good outcome in terms of low mortality and morbidity rates. It can achieve a
      durable valve-sparing repair, good functional mid-term outcomes and good quality
      of life among survivors.

PMID- 27702824
TI  - Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report
      from the Children's Oncology Group.
AB  - PURPOSE: To investigate the role and significance of TP53 mutation in diffusely
      anaplastic Wilms tumors (DAWTs). EXPERIMENTAL DESIGN: All DAWTs registered on
      National Wilms Tumor Study-5 (n = 118) with available samples were analyzed for
      TP53 mutations and copy loss. Integrative genomic analysis was performed on 39
      selected DAWTs. RESULTS: Following analysis of a single random sample, 57 DAWTs
      (48%) demonstrated TP53 mutations, 13 (11%) copy loss without mutation, and 48
      (41%) lacked both [defined as TP53-wild-type (wt)]. Patients with stage III/IV
      TP53-wt DAWTs (but not those with stage I/II disease) had significantly lower
      relapse and death rates than those with TP53 abnormalities. In-depth analysis of
      a subset of 39 DAWTs showed seven (18%) to be TP53-wt: These demonstrated gene
      expression evidence of an active p53 pathway. Retrospective pathology review of
      TP53-wt DAWT revealed no or very low volume of anaplasia in six of seven tumors.
      When samples from TP53-wt tumors known to contain anaplasia histologically were
      available, abnormal p53 protein accumulation was observed by
      immunohistochemistry. CONCLUSIONS: These data support the key role of TP53 loss
      in the development of anaplasia in WT, and support its significant clinical
      impact in patients with residual anaplastic tumor following surgery. These data
      also suggest that most DAWTs will show evidence of TP53 mutation when samples
      selected for the presence of anaplasia are analyzed. This suggests that
      modifications of the current criteria to also consider volume of anaplasia and
      documentation of TP53 aberrations may better reflect the risk of relapse and
      death and enable optimization of therapeutic stratification. Clin Cancer Res;
      22(22); 5582-91. (c)2016 AACR.

PMID- 27702830
TI  - What is the impact of preoperative aspirin administration on patients undergoing
      coronary artery bypass grafting?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether continuation of administration of
      preoperative aspirin until the day of coronary artery bypass grafting (CABG)
      could minimize postoperative mortality, prevalence of postoperative myocardial
      infarction (MI) with or without influence on postoperative bleeding, packed red
      blood cell (PRBC) transfusion and reoperation for bleeding. Altogether, 662
      papers were found using the reported search, 7 of which represented the best
      evidence to answer the clinical question. The authors, journal, date and country
      of publication, patient group studied, study type, relevant outcomes and results
      of these papers are tabulated. Seven studies, included in this review, consisted
      of five meta-analyses and two randomized controlled trials. One meta-analysis,
      involving 27 533 patients submitted to CABG, showed that the administration of
      preoperative aspirin decreased postoperative 30-day mortality by 27%. Another
      meta-analysis, including 1437 patients, showed that preoperative aspirin
      decreased the incidence of perioperative MI by 44%, the effect being even more
      pronounced with low-dose aspirin, which reduced the prevalence of perioperative
      MI by 63%. One RCT showed that preoperative aspirin is associated with reduced
      long-term hazard of MI or repeated revascularization. Four meta-analyses and two
      RCTs showed that preoperative aspirin is associated with increased postoperative
      bleeding, PRBC transfusion and reoperation for bleeding. However, this was not
      the case with preoperative administration of low-dose aspirin. The results
      presented in these studies suggest that preoperative aspirin administration in
      patients undergoing CABG has a significant benefit in reducing the incidence of
      perioperative MI and 30-day mortality rate, as well as reduced long-term hazard
      of MI or repeated revascularization. At a higher dose (>100 mg/day),
      postoperative bleeding, PRBC transfusion and reoperation for bleeding increased.
      However, with low-dose aspirin (<=100 mg/day), these benefits were not at the
      expense of increased postoperative bleeding or transfusion.

PMID- 27702831
TI  - Reduction of INCOR(r) driveline infection rate with silicone at the driveline
      exit site.
AB  - Objectives: A silicone interface at skin level of left ventricular assist device
      (LVAD) may reduce the risk of driveline (DL) exit site infections when compared
      with other materials (e.g. velour). The purpose of this study was to evaluate the
      rate of DL exit site infection according to the presence of silicone or velour at
      the exit site with the redesigned INCOR, facilitating the positioning of silicone
      at the exit site. Methods: The rate of DL exit site infection and overall
      survival were compared between the two groups (silicone group, n = 16/velour
      group, n = 24) with 1-year follow-up postimplantation. Results: Risk factors for
      infection were more prevalent in the silicone group (obesity P = 0.33, prevalence
      of renal dysfunction P = 0.007, higher CRP levels P = 0.001). During the
      observation period, 6 patients developed a DL infection (25%) in the velour
      group, whereas 1 patient developed a DL infection in (6%) in the silicone group
      (P = 0.19). The event-per-patient year (EPPY) rates were 0.34 and 0.10 for velour
      group and silicone group, respectively (P = 0.30). All DL infections could be
      treated successfully by the antibiotic treatment, surgical debridement and
      ultimately high urgency heart transplantation, resulting in no direct DL
      infection-related mortality in this cohort. One-year survival was similar in both
      the groups (silicone 69 vs 75% in the velour group; P = 0.67). Conclusions: Fewer
      infections were observed at the exit site in case of a silicone-covered DL,
      without reaching statistical significance. More patients and longer observation
      periods are needed to demonstrate a statistical difference.

PMID- 27702834
TI  - Systolic Blood Pressure and Risk of Type 2 Diabetes: A Mendelian Randomization
      Study.
AB  - Observational studies have shown that elevated systolic blood pressure (SBP) is
      associated with future onset of type 2 diabetes, but whether this association is
      causal is not known. We applied the Mendelian randomization framework to evaluate
      the causal hypothesis that elevated SBP increases risk for type 2 diabetes. We
      used 28 genetic variants associated with SBP and evaluated their impact on type 2
      diabetes using a European-centric meta-analysis comprising 37,293 case and
      125,686 control subjects. We found that elevation of SBP levels by 1 mmHg due to
      our genetic score was associated with a 2% increase in risk of type 2 diabetes
      (odds ratio 1.02, 95% CI 1.01-1.03, P = 9.05 * 10-5). To limit confounding, we
      constructed a second score based on 13 variants exclusively associated with SBP
      and found a similar increase in type 2 diabetes risk per 1 mmHg of genetic
      elevation in SBP (odds ratio 1.02, 95% CI 1.01-1.03, P = 1.48 * 10-3).
      Sensitivity analyses using multiple, alternative causal inference measures and
      simulation studies demonstrated consistent association, suggesting robustness of
      our primary observation. In line with previous reports from observational
      studies, we found that genetically elevated SBP was associated with increased
      risk for type 2 diabetes. Further work will be required to elucidate the
      biological mechanism and translational implications.

PMID- 27702835
TI  - Comparative evaluation of three new commercial immunoassays for anti-Mullerian
      hormone measurement.
AB  - STUDY QUESTION: How do the three new anti-Mullerian hormone (AMH) assay methods,
      manufactured by Beckman Coulter, Roche and Ansh Labs compare with each other and
      with the Gen II assay? SUMMARY ANSWER: The three new AMH assays are well
      correlated among themselves and with the Gen II assay, although differences in
      calibration do exist. WHAT IS KNOWN ALREADY: The Gen II assay has been the
      mainstay method for AMH measurement in the past few years. Recently, a few new
      AMH measurement methods have come to the market. STUDY DESIGN, SIZE, DURATION:
      This was a prospective assay evaluation performed on 178 human serum samples.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: AMH concentration was measured in
      residual serum samples donated by female patients in a reproductive medicine
      centre. The three new assay methods were tested in parallel and the numerical
      values obtained were compared among themselves and with those obtained by the Gen
      II assay. The assay stability upon different sample storage conditions, intra
      assay and inter-assay precision, linearity and dilution recovery, and diagnostic
      performance for polycystic ovary syndrome (PCOS) of the three new AMH assay
      methods were also compared. MAIN RESULTS AND THE ROLE OF CHANCE: AMH values
      measured by the Gen II kit and the three new assay methods have good correlations
      (R > 0.9 for all pairwise correlations). Values measured by the Ansh Labs assay
      were significantly higher, whereas those by the Roche assay were significantly
      lower, than those from the Gen II and Beckman-Coulter automated assays (P <
      0.05). AMH values were significantly different when measured on the fresh and
      frozen-thawed serum sample (at -20oC and -80oC) for all three new methods (P <
      0.05), but the magnitude of difference was very small with the Beckman-Coulter
      automated assay and Roche assay. The intra-assay coefficients of variation (CVs)
      were 0.7-2.2%, 0.5-1.4%, and 1.4-5.4% for the Beckman-Counter automated, Roche
      and Ansh Labs assays, respectively. Their inter-assay CVs were 0.9-2.5%, 0.7
      1.9%, and 6.2-13.5%, respectively. All three new assay methods showed acceptable
      linearity, and provided excellent discrimination of PCOS from controls.
      LIMITATIONS, REASONS FOR CAUTION: The precision and dilution linearity
      experiments involved a small sample size, although these were not the primary
      outcome measures and have been properly evaluated in previous publications. The
      study was not designed or powered for determining diagnostic cut-off values.
      WIDER IMPLICATIONS OF THE FINDINGS: The results demonstrate that the three new
      AMH assay methods are all valid methods to be adopted in the field of
      reproduction and are a basis for further work on their clinical application.
      STUDY FUNDING/COMPETING INTERESTS: The authors have no competing interest to
      declare. The execution of this study was funded by the Department of Obstetrics
      and Gynaecology, The University of Hong Kong.

PMID- 27702832
TI  - Impact of Perturbed Pancreatic beta-Cell Cholesterol Homeostasis on Adipose
      Tissue and Skeletal Muscle Metabolism.
AB  - Elevated pancreatic beta-cell cholesterol levels impair insulin secretion and
      reduce plasma insulin levels. This study establishes that low plasma insulin
      levels have a detrimental effect on two major insulin target tissues: adipose
      tissue and skeletal muscle. Mice with increased beta-cell cholesterol levels were
      generated by conditional deletion of the ATP-binding cassette transporters, ABCA1
      and ABCG1, in beta-cells (beta-DKO mice). Insulin secretion was impaired in these
      mice under basal and high-glucose conditions, and glucose disposal was shifted
      from skeletal muscle to adipose tissue. The beta-DKO mice also had increased body
      fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP
      1 levels, and decreased skeletal muscle mass. They were not, however, insulin
      resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not
      the systemic inflammation or increased adipose tissue macrophage content, were
      reversed when plasma insulin levels were normalized by insulin supplementation.
      These studies identify a mechanism by which perturbation of beta-cell cholesterol
      homeostasis and impaired insulin secretion increase adiposity, reduce skeletal
      muscle mass, and cause systemic inflammation. They further identify beta-cell
      dysfunction as a potential therapeutic target in people at increased risk of
      developing type 2 diabetes.

PMID- 27702836
TI  - The predictive value of 18F-FDG PET for pathological response of primary tumor in
      patients with esophageal cancer during or after neoadjuvant chemoradiotherapy: a
      meta-analysis.
AB  - OBJECTIVE: We want to review the value of 18-fluoro-deoxy-glucose positron
      emission tomography for response prediction of primary tumor in patients with
      esophageal cancer during or after neoadjuvant chemoradiotherapy. METHODS: Studies
      were searched in Pubmed, Embase and Cochrane Library with specific search
      strategy. The published articles were included according to the criteria
      established in advance. The included studies were divided into two groups
      according to the time of the repeat positron emission tomography: during (Group
      A) or after neoadjuvant chemoradiotherapy (Group B). The studies that performed
      the repeat positron emission tomography after neoadjuvant chemoradiotherapy were
      graded Quality Assessment of Diagnostic Accuracy Studies. The pooled sensitivity,
      specificity and diagnostic odds ratio were obtained for both groups on the basis
      of no-existing of threshold effect. RESULTS: Fifteen studies were included in the
      present study. The threshold effect did not exist in both groups. The pooled
      sensitivity, specificity and diagnostic odds ratio were 85%, 59%, 6.82 with 95%
      confidence interval 76-91%, 48-69%, 2.25-20.72 in Group A. The equivalent values
      were 67%, 69%, 6.34 with 95% confidence interval 60-73%, 63-74%, 2.08-19.34 in
      Group B. The pooled sensitivity was 90% in four studies that enrolled patients
      with esophageal squamous cell carcinoma merely in Group B. CONCLUSIONS: According
      to the present data, positron emission tomography should not be used routinely to
      guide treatment strategy in esophageal cancer patients. We speculated that
      positron emission tomography could be used as a tool to predict treatment
      response after neoadjuvant chemoradiotherapy in patients with esophageal squamous
      cell carcinoma.

PMID- 27702833
TI  - Compensatory Hyperconnectivity in Developing Brains of Young Children With Type 1
      Diabetes.
AB  - Sustained dysregulation of blood glucose (hyper- or hypoglycemia) associated with
      type 1 diabetes (T1D) has been linked to cognitive deficits and altered brain
      anatomy and connectivity. However, a significant gap remains with respect to how
      T1D affects spontaneous at-rest connectivity in young developing brains. Here,
      using a large multisite study, resting-state functional MRI data were examined in
      young children with T1D (n = 57; mean age = 7.88 years; 27 females) as compared
      with age-matched control subjects without diabetes (n = 26; mean age = 7.43
      years; 14 females). Using both model-driven seed-based analysis and model-free
      independent component analysis and controlling for age, data acquisition site,
      and sex, converging results were obtained, suggesting increased connectivity in
      young children with T1D as compared with control subjects without diabetes.
      Further, increased connectivity in children with T1D was observed to be
      positively associated with cognitive functioning. The observed positive
      association of connectivity with cognitive functioning in T1D, without overall
      group differences in cognitive function, suggests a putative compensatory role of
      hyperintrinsic connectivity in the brain in children with this condition.
      Altogether, our study attempts to fill a critical gap in knowledge regarding how
      dysglycemia in T1D might affect the brain's intrinsic connectivity at very young
      ages.

PMID- 27702837
TI  - Role of multimodality therapy in cIIIA-N2 non-small cell lung cancer:
      perspective.
AB  - A number of promising new approaches for both local and systemic control of
      locally advanced non-small cell lung cancer have been examined in clinical
      trials, aimed at improving the patient survival. Development of better systemic
      therapies by adopting newer agents (such as epidermal growth factor receptor
      tyrosine kinase inhibitors and immune checkpoint inhibitors) from advanced non
      small cell lung cancer is mandatory. As for radiotherapy, adaptive radiotherapy
      and proton therapy are under investigation after the RTOG 0617 trial unexpectedly
      failed to show the efficacy of high-dose radiotherapy for Stage III disease. To
      date, no Phase III trial has clearly shown the benefit of adding surgery as a
      part of multimodality therapy for locally advanced non-small cell lung cancer.
      Such poor progress in the development of effective treatments for Stage III non
      small cell lung cancer is considered to be attributable to the existence of
      heterogeneities in the disease characteristics, including the biological and
      anatomic characteristics. Constant effort via well-designed and well-conducted
      clinical trials is needed to decipher the heterogeneity of Stage III non-small
      cell lung cancer.

PMID- 27702838
TI  - Growing Older With a Physical Disability: A Special Application of the Successful
      Aging Paradigm.
AB  - Objectives: In the United States, the average age of people living with early
      acquired physical disabilities is increasing. This cohort is said to be aging
      with disability and represents a unique population among older adults. Given
      recent policy efforts designed to merge aging and disability services, it is
      critical that models of "successful aging" include and are relevant to this
      population. However, many current definitions of successful aging emphasize
      avoidance of disability and high levels of physical function as necessary to well
      being. Method: In 9 focus groups, we examined perspectives of "successful aging"
      in 49 middle-aged and older individuals living with spinal cord injury, multiple
      sclerosis, muscular dystrophy, or postpolio syndrome. Transcripts were analyzed
      using a structured qualitative coding approach and Dedoose indexing software.
      Results: Participants ranged in age from 45 to 80 years (M = 62) and had lived
      with their disability diagnosis for an average of 21 years. Analysis revealed 4
      primary themes of successful aging: resilience/adaptation, autonomy, social
      connectedness, and physical health (including access to general and specialty
      healthcare). Discussion: Results highlight the need for a nuanced application of
      the "successful aging" paradigm in this population.

PMID- 27702839
TI  - Information and Communication Technology Use Is Related to Higher Well-Being
      Among the Oldest-Old.
AB  - Objectives: Older adults often prioritize socially meaningful goals over
      informational goals. Thus, we predicted that using information and communication
      technology (ICT) in service of socially meaningful versus informational goals
      relates to higher well-being among the oldest-old. Method: We surveyed 445 adults
      aged 80+ (mean = 84, range = 80-93; 64% female; 26% non-White) online or via
      telephone. Participants reported motivations for ICT use (connect with others,
      learn new information) and rated their psychological and physical well-being
      (i.e., life satisfaction, loneliness, goal attainment, subjective health,
      functional limitations). We conducted regression and mediation analyses to test
      our hypothesis. Results: Participants used ICT more to connect with
      friends/family (M = 3.66, SD = 1.28) than to learn information (M = 2.61, SD =
      1.44), p < .001. Overall, ICT use predicted higher well-being across outcomes, ps
      <= .008. Motivations for use differentially mediated these effects: Social
      motivations mediated the relationships between ICT use and psychological well
      being, whereas informational motivations mediated the relationships between ICT
      use and physical well-being. Discussion: Older adults aged 80+ use ICT less than
      other generations, but may have much to gain. Using social versus informational
      technologies may enhance multiple aspects of well-being in different ways during
      very late life. Highlighting such benefits may increase ICT adoption among the
      oldest-old.

PMID- 27702840
TI  - Instrumental- and Emotion-Focused Care Work During Physical Health Events:
      Comparing Gay, Lesbian, and Heterosexual Marriages.
AB  - Objectives: We consider emotion- and instrumental-focused care work and marital
      stress during significant physical health events in midlife gay, lesbian, and
      heterosexual marriages. Method: We employ the factorial method, an extension of
      the actor-partner interdependence model, to analyze survey data from 808 midlife
      gay, lesbian, and heterosexual spouses in 404 unions. Results: The amount of
      emotion- and instrumental-focused care work provided during physical health
      events, and the associations between care work and marital stress, depends on the
      gender of the respondent, gender of the spouse, and whether spouses are in a same
      sex or different-sex union. For example, in both same- and different-sex
      marriages, women report providing more emotion-focused care work during their own
      health event than do men, and respondents report more health-related marital
      stress when the patient is a woman. Discussion: Investigating how midlife same
      sex and different-sex spouses care for each other during a spouse's health event
      expands understandings of gendered aging experiences within marriage. Findings
      can elucidate health policies and clinical strategies that best support the
      health of men and women in same- and different-sex marriages.

PMID- 27702841
TI  - Regulation of Stomatal Defense by Air Relative Humidity.
AB  - It has long been observed that environmental conditions play crucial roles in
      modulating immunity and disease in plants and animals. For instance, many
      bacterial plant disease outbreaks occur after periods of high humidity and rain.
      A critical step in bacterial infection is entry into the plant interior through
      wounds and natural openings, such as stomata, which are adjustable microscopic
      pores in the epidermal tissue. Several studies have shown that stomatal closure
      is an integral part of the plant immune response to reduce pathogen invasion. In
      this study, we found that high humidity can effectively compromise Pseudomonas
      syringae-triggered stomatal closure in both Phaseolus vulgaris and Arabidopsis
      (Arabidopsis thaliana), which is accompanied by early up-regulation of the
      jasmonic acid (JA) pathway and simultaneous down-regulation of salicylic acid
      (SA) pathway in guard cells. Furthermore, SA-dependent response, but not JA
      dependent response, is faster in guard cells than in whole leaves, suggesting
      that the SA signaling in guard cells may be independent from other cell types.
      Thus, we conclude that high humidity, a well-known disease-promoting
      environmental condition, acts in part by suppressing stomatal defense and is
      linked to hormone signaling in guard cells.

PMID- 27702844
TI  - The Thiamine Biosynthesis Gene THI1 Promotes Nodule Growth and Seed Maturation.
AB  - Thiamine (vitamin B1) is essential for living organisms. Unlike animals, plants
      can synthesize thiamine. In Lotus japonicus, the expression of two thiamine
      biosynthesis genes, THI1 and THIC, was enhanced by inoculation with rhizobia but
      not by inoculation with arbuscular mycorrhizal fungi. THIC and THI2 (a THI1
      paralog) were expressed in uninoculated leaves. THI2-knockdown plants and the
      transposon insertion mutant thiC had chlorotic leaves. This typical phenotype of
      thiamine deficiency was rescued by an exogenous supply of thiamine. In wild-type
      plants, THI1 was expressed mainly in roots and nodules, and the thi1 mutant had
      green leaves even in the absence of exogenous thiamine. THI1 was highly expressed
      in actively dividing cells of nodule primordia. The thi1 mutant had small
      nodules, and this phenotype was rescued by exogenous thiamine and by THI1
      complementation. Exogenous thiamine increased nodule diameter, but the level of
      arbuscular mycorrhizal colonization was unaffected in the thi1 mutant or by
      exogenous thiamine. Expression of symbiotic marker genes was induced normally,
      implying that mainly nodule growth was delayed in the thi1 mutant. Furthermore,
      this mutant formed many immature seeds with reduced seed weight. These results
      indicate that thiamine biosynthesis mediated by THI1 enhances nodule enlargement
      and is required for seed development in L. japonicus.

PMID- 27702843
TI  - OsHAC1;1 and OsHAC1;2 Function as Arsenate Reductases and Regulate Arsenic
      Accumulation.
AB  - Rice is a major dietary source of the toxic metalloid arsenic (As). Reducing its
      accumulation in rice (Oryza sativa) grain is of critical importance to food
      safety. Rice roots take up arsenate and arsenite depending on the prevailing soil
      conditions. The first step of arsenate detoxification is its reduction to
      arsenite, but the enzyme(s) catalyzing this reaction in rice remains unknown.
      Here, we identify OsHAC1;1 and OsHAC1;2 as arsenate reductases in rice. OsHAC1;1
      and OsHAC1;2 are able to complement an Escherichia coli mutant lacking the
      endogenous arsenate reductase and to reduce arsenate to arsenite. OsHAC1:1 and
      OsHAC1;2 are predominantly expressed in roots, with OsHAC1;1 being abundant in
      the epidermis, root hairs, and pericycle cells while OsHAC1;2 is abundant in the
      epidermis, outer layers of cortex, and endodermis cells. Expression of the two
      genes was induced by arsenate exposure. Knocking out OsHAC1;1 or OsHAC1;2
      decreased the reduction of arsenate to arsenite in roots, reducing arsenite
      efflux to the external medium. Loss of arsenite efflux was also associated with
      increased As accumulation in shoots. Greater effects were observed in a double
      mutant of the two genes. In contrast, overexpression of either OsHAC1;1 or
      OsHAC1;2 increased arsenite efflux, reduced As accumulation, and enhanced
      arsenate tolerance. When grown under aerobic soil conditions, overexpression of
      either OsHAC1;1 or OsHAC1;2 also decreased As accumulation in rice grain, whereas
      grain As increased in the knockout mutants. We conclude that OsHAC1;1 and
      OsHAC1;2 are arsenate reductases that play an important role in restricting As
      accumulation in rice shoots and grain.

PMID- 27702842
TI  - Developmental Control and Plasticity of Fruit and Seed Dimorphism in Aethionema
      arabicum.
AB  - Understanding how plants cope with changing habitats is a timely and important
      topic in plant research. Phenotypic plasticity describes the capability of a
      genotype to produce different phenotypes when exposed to different environmental
      conditions. In contrast, the constant production of a set of distinct phenotypes
      by one genotype mediates bet hedging, a strategy that reduces the temporal
      variance in fitness at the expense of a lowered arithmetic mean fitness. Both
      phenomena are thought to represent important adaptation strategies to unstable
      environments. However, little is known about the underlying mechanisms of these
      phenomena, partly due to the lack of suitable model systems. We used phylogenetic
      and comparative analyses of fruit and seed anatomy, biomechanics, physiology, and
      environmental responses to study fruit and seed heteromorphism, a typical
      morphological basis of a bet-hedging strategy of plants, in the annual
      Brassicaceae species Aethionema arabicum Our results indicate that heteromorphism
      evolved twice within the Aethionemeae, including once for the monophyletic annual
      Aethionema clade. The dimorphism of Ae. arabicum is associated with several
      anatomic, biomechanical, gene expression, and physiological differences between
      the fruit and seed morphs. However, fruit ratios and numbers change in response
      to different environmental conditions. Therefore, the life-history strategy of
      Ae. arabicum appears to be a blend of bet hedging and plasticity. Together with
      the available genomic resources, our results pave the way to use this species in
      future studies intended to unravel the molecular control of heteromorphism and
      plasticity.

PMID- 27702846
TI  - Fluoxetine vs. placebo for the treatment of recurrent vasovagal syncope with
      anxiety sensitivity.
AB  - AIMS: The optimal medical therapy of patients with vasovagal syncope (VVS)
      remains controversial. Fluoxetine is effective against anxiety and panic
      disorders, while its use has shown promising results for VVS. Anxiety sensitivity
      is a personality trait observed in a considerable proportion of patients with
      VVS, associated with predisposition to anxiety and panic disorders. Our aim was
      to examine whether fluoxetine exerts beneficial effects regarding VVS prevention
      in the subset of patients with anxiety sensitivity. METHODS AND RESULTS: We
      assessed 106 patients with typical history of recurrent VVS, without other
      comorbidities, and a diagnostic, positive head-up tilt test. A psychiatric
      examination ruled out clinical psychiatric disease. Their psychological, stress
      related profile was assessed by the Anxiety Sensitivity Index (ASI)
      questionnaire, a 16-item questionnaire, assessing fear of anxiety-related
      sensations, previously studied in VVS. Patients scoring positive for ASI (n = 60,
      57% of the population) were randomized in a 2:1 fashion to receive either 10-40
      mg fluoxetine daily (n = 40) or placebo (n = 20), and were followed-up for 1
      year. A significant difference was observed between patients receiving fluoxetine
      and those with placebo, regarding the distribution of syncope-free time during
      the study (P < 0.05). A significant difference was also observed between the two
      groups regarding presyncopal events and the total number of patients who
      experienced syncope or presyncope during follow-up. CONCLUSION: Sensitivity to
      anxiety is a common personality trait in recurrent VVS. Fluoxetine is superior to
      placebo against syncope in these patients. This drug may be a first-line
      pharmacological treatment for this difficult-to-treat group.

PMID- 27702845
TI  - Phytoglobins Improve Hypoxic Root Growth by Alleviating Apical Meristem Cell
      Death.
AB  - Hypoxic root growth in maize (Zea mays) is influenced by the expression of
      phytoglobins (ZmPgbs). Relative to the wild type, suppression of ZmPgb1.1 or
      ZmPgb1.2 inhibits the growth of roots exposed to 4% oxygen, causing structural
      abnormalities in the root apical meristems. These effects were accompanied by
      increasing levels of reactive oxygen species (ROS), possibly through the
      transcriptional induction of four Respiratory Burst Oxidase Homologs TUNEL
      positive nuclei in meristematic cells indicated the involvement of programmed
      cell death (PCD) in the process. These cells also accumulated nitric oxide and
      stained heavily for ethylene biosynthetic transcripts. A sharp increase in the
      expression level of several 1-aminocyclopropane synthase (ZmAcs2, ZmAcs6, and
      ZmAcs7), 1-aminocyclopropane oxidase (Aco15, Aco20, Aco31, and Aco35), and
      ethylene-responsive (ZmErf2 and ZmEbf1) genes was observed in hypoxic ZmPgb
      suppressing roots, which overproduced ethylene. Inhibiting ROS synthesis with
      diphenyleneiodonium or ethylene perception with 1-methylcyclopropene suppressed
      PCD, increased BAX inhibitor-1, an effective attenuator of the death programs in
      eukaryotes, and restored root growth. Hypoxic roots overexpressing ZmPgbs had the
      lowest level of ethylene and showed a reduction in ROS staining and TUNEL
      positive nuclei in the meristematic cells. These roots retained functional
      meristems and exhibited the highest growth performance when subjected to hypoxic
      conditions. Collectively, these results suggest a novel function of Pgbs in
      protecting root apical meristems from hypoxia-induced PCD through mechanisms
      initiated by nitric oxide and mediated by ethylene via ROS.

PMID- 27702847
TI  - Termination of persistent atrial fibrillation during pulmonary vein isolation:
      insight from the MAGIC-AF trial.
AB  - Aims: Controversy on the optimal ablation strategy for persistent atrial
      fibrillation (AF) exists with limited work evaluating a strategy of pulmonary
      vein isolation (PVI) alone when AF terminates during PVI. Thirty-five patients
      had AF termination during PVI in the Modified Ablation Guided by Ibutilide Use in
      Chronic Atrial Fibrillation (MAGIC-AF; ClinicalTrials.gov number: NCT01014741)
      study. The objective of the current study is to report the 1-year outcome after
      PVI alone in this unique patient group. Methods and results: The 1-year single
      procedure freedom from atrial arrhythmia off anti-arrhythmic drugs was reported
      for the 35 patients in the MAGIC-AF study with persistent AF termination during
      or upon completion of PVI. Freedom from recurrent atrial arrhythmia was achieved
      in 60% of patients where AF terminated during PVI. Cavotricuspid isthmus flutter
      was common when AF terminated to a macro re-entrant flutter during PVI, and
      responsible for 92% of all flutter circuits with AF termination. Conclusions:
      Persistent AF termination during PVI may identify a subgroup of patients who
      experience a similar long-term clinical outcome with PVI ablation alone when
      compared with other more extensive persistent AF ablation strategies. Pulmonary
      vein isolation alone may be an appropriate tactic in this subgroup of persistent
      AF patients.

PMID- 27702849
TI  - Time matters: adenosine testing immediately after pulmonary vein isolation does
      not substitute a waiting period.
AB  - Aims: Adenosine testing can reveal dormant pulmonary vein (PV) conduction after
      PV antrum isolation (PVAI). However, the optimal timing for adenosine
      administration is unknown. We hypothesized that adenosine testing immediately
      after PVAI reliably reveals PV reconnection and thereby eliminates the need for
      an observation period. Methods and results: Fifty patients underwent PVAI.
      Immediately after isolation of a PV pair, adenosine was administered. Both PV
      pairs were separately tested. If adenosine restored PV conduction, PVs were re
      isolated. During a >=30 min observation period after immediate adenosine-guided
      isolation, spontaneous reconnection was assessed and reconnected PVs were re
      isolated. After the observation period, adenosine testing was repeated. Immediate
      adenosine testing revealed dormant conduction in 10.4% of the left PVs and 16.3%
      of the right PVs. All PVs were successfully re-isolated. During a mean
      observation period of 36 +/- 10 min, spontaneous reconnection occurred in 8.2% of
      the left and 16.3% of the right PVs. None of these PVs had shown reconnection
      during immediate testing. Late adenosine testing revealed dormant conduction in
      12.5% of the left and 16.3% of the right PVs. In patients without reconnection
      during immediate adenosine testing, 14.6% of the left PVs and 30.6% of the right
      PVs showed either spontaneous reconnection or restored PV conduction during late
      adenosine testing. Conclusion: Adenosine testing immediately after PVAI does not
      reliably exclude later spontaneous or adenosine-induced PV reconnection.
      Adenosine testing should be performed after an appropriate observation period to
      reduce risk of PV reconnection.

PMID- 27702848
TI  - Contemporary rates and outcomes of single- vs. dual-coil implantable cardioverter
      defibrillator lead implantation: data from the Israeli ICD Registry.
AB  - Aims: Dual-coil leads were traditionally considered standard of care due to lower
      defibrillation thresholds (DFT). Higher complication rates during extraction with
      parallel progression in implantable cardioverter defibrillator (ICD) technology
      raised questions on dual coil necessity. Prior substudies found no significant
      outcome difference between dual and single coils, although using higher rates of
      DFT testing then currently practiced. We evaluated the temporal trends in
      implantation rates of single- vs. dual-coil leads and determined the associated
      adverse clinical outcomes, using a contemporary nation-wide ICD registry. Methods
      and results: Between July 2010 and March 2015, 6343 consecutive ICD (n = 3998) or
      CRT-D (n = 2345) implantation patients were prospectively enrolled in the Israeli
      ICD Registry. A follow-up of at least 1 year of 2285 patients was available for
      outcome analysis. The primary endpoint was all-cause mortality. Single-coil leads
      were implanted in 32% of our cohort, 36% among ICD recipients, and 26% among CRT
      D recipients. Secondary prevention indication was associated with an increased
      rate of dual-coil implantation. A significant decline in dual-coil leads with
      reciprocal incline of single coils was observed, despite low rates of DFT testing
      (11.6%) during implantation, which also declined from 31 to 2%. In the
      multivariate Cox model analysis, dual- vs. single-coil lead implantation was not
      associated with an increased risk of mortality [hazard ratio (HR) = 1.23; P=
      0.33], heart failure hospitalization (HR = 1.34; P=0.13), appropriate (HR = 1.25;
      P= 0.33), or inappropriate ICD therapy (HR = 2.07; P= 0.12). Conclusion: Real
      life rates of single-coil lead implantation are rising while adding no additional
      risk. These results of single-coil safety are reassuring and obtained, despite
      low and contemporary rates of DFT testing.

PMID- 27702850
TI  - Traditional and novel electrocardiographic conduction and repolarization markers
      of sudden cardiac death.
AB  - Sudden cardiac death, frequently due to ventricular arrhythmias, is a significant
      problem globally. Most affected individuals do not arrive at hospital in time for
      medical treatment. Therefore, there is an urgent need to identify the most-at
      risk patients for insertion of prophylactic implantable cardioverter
      defibrillators. Clinical risk markers derived from electrocardiography are
      important for this purpose. They can be based on repolarization, including
      corrected QT (QTc) interval, QT dispersion (QTD), interval from the peak to the
      end of the T-wave (Tpeak - Tend), (Tpeak - Tend)/QT, T-wave alternans (TWA), and
      microvolt TWA. Abnormal repolarization properties can increase the risk of
      triggered activity and re-entrant arrhythmias. Other risk markers are based
      solely on conduction, such as QRS duration (QRSd), which is a surrogate marker of
      conduction velocity (CV) and QRS dispersion (QRSD) reflecting CV dispersion.
      Conduction abnormalities in the form of reduced CV, unidirectional block,
      together with a functional or a structural obstacle, are conditions required for
      circus-type or spiral wave re-entry. Conduction and repolarization can be
      represented by a single parameter, excitation wavelength (lambda = CV * effective
      refractory period). lambda is an important determinant of arrhythmogenesis in
      different settings. Novel conduction-repolarization markers incorporating lambda
      include Lu et al.' index of cardiac electrophysiological balance (iCEB: QT/QRSd),
      [QRSD* (Tpeak - Tend)/QRSd] and [QRSD * (Tpeak - Tend)/(QRSd * QT)] recently
      proposed by Tse and Yan. The aim of this review is to provide up to date
      information on traditional and novel markers and discuss their utility and
      downfalls for risk stratification.

PMID- 27702851
TI  - The wearable cardioverter-defibrillator: current technology and evolving
      indications.
AB  - The wearable cardioverter-defibrillator has been available for over a decade and
      now is frequently prescribed for patients deemed at high arrhythmic risk in whom
      the underlying pathology is potentially reversible or who are awaiting an
      implantable cardioverter-defibrillator. The use of the wearable cardioverter
      defibrillator is included in the new 2015 ESC guidelines for the management of
      ventricular arrhythmias and prevention of sudden cardiac death. The present
      review provides insight into the current technology and an overview of this
      approach.

PMID- 27702853
TI  - Left atrial model reconstruction in atrial fibrillation ablation: reliability of
      new mapping and complex impedance systems.
AB  - Aims: The effectiveness of atrial fibrillation (AF) ablation relies on detailed
      knowledge of the anatomy of the left atrium (LA) and pulmonary veins (PVs). It is
      common to combine computed tomography/magnetic resonance (CT/MR) with imaging by
      electroanatomical (EA) mapping systems. The aim of this study was to evaluate the
      accuracy of LA anatomical reconstruction by 'One Model' and 'VeriSense' tools
      (Ensite Velocity 3.0, St Jude Medical), compared with CT/MR imaging. Methods and
      results: Seventy-two patients with AF underwent pre-procedural imaging (97% CT
      scan, 3% MR imaging) and transcatheter ablation of PVs. Operators were blinded to
      CT/MR imaging. Electrical Coupling Index (ECI) was used to recognize venous
      structures when the circular catheter could not. The LA 'One Model' map was
      obtained without complications; all 124 main left PVs and 144 main right PVs were
      detected. Nine of 9 intermediate right PVs and 30 of 30 early branches were
      detected, whereas 1 of the 27 early branches on the right inferior PVs was
      missed. Comparison between LA intervein distances measured on the roof (RO) and
      the posterior wall (PW) showed a high correspondence between the EA model and
      CT/MR imaging (RO CT/MR imaging vs. EA: 32 +/- 7 vs. 32 +/- 7 mm; PW CT/MR
      imaging vs. EA: 36 +/- 6 vs. 36 +/- 7 mm). The EA model yielded slightly larger
      PV ostia diameters, owing to the distortion caused by catheter pressure.
      Conclusions: Recent 3D mapping tools allow outstanding anatomical rendering and
      are key in complex ablation procedure set-up. This study shows that 3D anatomical
      reconstruction of LA, PVs, and their variable branches is not only safe and fast
      but also accurate and reliable.

PMID- 27702852
TI  - Antiadrenergic autoimmunity in postural tachycardia syndrome.
AB  - Aims: Postural tachycardia syndrome (POTS), a common and debilitating
      cardiovascular disorder, is characterized by an exaggerated heart rate increase
      during orthostasis and a wide spectrum of adrenergic-related symptoms. To
      determine the aetiology of POTS, we examined a possible pathophysiological role
      for autoantibodies against alpha1-adrenergic (alpha1AR) and beta1/2-adrenergic
      receptors (beta1/2AR). Methods and results: Immunoglobulin G (IgG) derived from
      17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal
      controls was analysed for its ability to modulate activity and ligand
      responsiveness of alpha1AR and beta1/2AR in transfected cells and to alter
      contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G
      activation of alpha1AR and beta1/2AR was significantly higher in POTS compared
      with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS
      patients possessed autoantibodies that activated alpha1AR, beta1AR and beta2AR,
      respectively. Pharmacological blockade suppressed IgG-induced activation of
      alpha1AR and beta1/2AR. Eight of 17 POTS IgG decreased the alpha1AR
      responsiveness to phenylephrine and 13 of 17 POTS IgG increased the beta1AR
      responsiveness to isoproterenol irrespective of their ability to directly
      activate their receptors. Postural tachycardia syndrome IgG contracted rat
      cremaster arterioles, which was reversed by alpha1AR blockade. The upright heart
      rate correlated with IgG-mediated beta1AR and alpha1AR activity but not with
      beta2AR activity. Conclusion: These data confirm a strong relationship between
      adrenergic autoantibodies and POTS. They support the concept that allosteric
      mediated shifts in the alpha1AR and beta1AR responsiveness are important in the
      pathophysiology of postural tachycardia.

PMID- 27702854
TI  - Incidence of silent cerebral infarctions after catheter ablation of atrial
      fibrillation utilizing the second-generation cryoballoon.
AB  - Aims: Pulmonary vein (PV) isolation (PVI) utilizing a cryoballoon (CB) has become
      one of the standard therapeutic options for atrial fibrillation (AF). However, it
      connotes a potential risk of cerebral ischaemic events (CIEs). This study aimed
      to clarify the prevalence of CIEs after PVI using second-generation CBs assessed
      by magnetic resonance imaging (MRI) of the brain. Methods and results: This
      prospective observational study consisted of 160 patients that underwent PVI with
      second-generation CBs for drug-refractory AF. Irrigated radiofrequency (RF)
      ablation for 'touch-up' procedures was utilized when conduction gaps between the
      left atrium (LA) and PVs were found after the CB application. Radiofrequency
      linear ablation was added in select patients. Cerebral MRI and neurological
      examinations were performed on the day following the ablation procedure. The MRI
      depicted micro-cerebral infarctions in 43 patients (26.9%, 1.49 lesions per
      case). All patients were free from symptomatic focal neurological deficits. Touch
      up ablation was required for the PVI establishment in 35 patients (21.9%). Linear
      ablation was performed in 59 patients (36.9%). Additional RF ablation within the
      LA was an independent risk of CIEs in the uni- and multivariate analyses. When
      the analyses were limited to patients who had undergone only CB ablation, CIEs
      were found in 12 of 66 patients (18.2%). Conclusion: Pulmonary vein isolation
      utilizing second-generation CBs carries a negligible risk of symptomatic CIEs;
      however, it includes a comparable risk of asymptomatic CIEs as in the previous
      similar reports using the first-generation CB. Radiofrequency applications in
      addition to the CB within the LA were the only predictor of this adverse effect.

PMID- 27702855
TI  - Simultaneous display of multiple three-dimensional electrophysiological datasets
      (dot mapping).
AB  - Aims: Complex ablation procedures are supported by accurate representation of an
      increasing variety of electrophysiological and imaging data within
      electroanatomic mapping systems (EMS). This study aims to develop a novel method
      for representing multiple complementary datasets on a single cardiac chamber
      model. Validation of the system and its application to both atrial and
      ventricular arrhythmias is examined. Methods and results: Dot mapping was
      conceived to display multiple datasets by utilizing quantitative surface shading
      to represent one dataset and finely spaced dots to represent others. Dot
      positions are randomized within triangular (surface meshes) or tetrahedral
      (volumetric meshes) simplices making the approach directly transferrable to
      contemporary EMS. Test data representing uniform electrical activation (n = 10)
      and focal scarring (n = 10) were used to test dot mapping data perception
      accuracy. User experience of dot mapping with atrial and ventricular clinical
      data is evaluated. Dot mapping ensured constant screen dot density for regions of
      uniform dataset values, regardless of user manipulation of the cardiac chamber.
      Perception accuracy of dot mapping was equivalent to colour mapping for both
      propagation direction (1.5 +/- 1.8 vs. 4.8 +/- 5.3 degrees , P = 0.24) and focal
      source localization (1.1 +/- 0.7 vs. 1.4 +/- 0.5 mm, P = 0.88). User acceptance
      testing revealed equivalent diagnostic accuracy and display fidelity when
      compared with colour mapping. Conclusion: Dot mapping provides the unique ability
      to display multiple datasets from multiple sources on a single cardiac chamber
      model. The visual combination of multiple datasets may facilitate interpretation
      of complex electrophysiological and imaging data.

PMID- 27702856
TI  - Atrial arrhythmia after transcatheter closure of secundum atrial septal defects
      in patients >=40 years of age.
AB  - Aim: Data on arrhythmia outcome following device closure of atrial septal defect
      (ASD) are lacking. This study provides medium-term follow-up data on atrial
      arrhythmias in patients who were >=40 years of age at the time of transcatheter
      ASD closure. Methods and results: It is a retrospective review. Mean age of the
      159 patients was 57 years. Median follow-up was 3.6 years (range 6 months-10.9
      years). Patients were classified, according to arrhythmia status prior to ASD
      closure, into Group I, no history of atrial arrhythmia (n = 119, mean age 55.5
      years); Group II, paroxysmal atrial arrhythmia (n = 18, mean age 55.7 years); and
      Group III, persistent atrial fibrillation (n = 22, mean age 65.7 years). Group
      III patients were significantly older, had larger left atrial size, and had
      higher mean pulmonary arterial pressure than Group I and II patients (P < 0.001).
      Prior to closure, radiofrequency ablation was carried out in 12/18 (66%) of Group
      II and 3/22 (14%) of Group III. After device closure, 7 patients (6%) of Group I
      developed new atrial fibrillation. Fifty per cent (9/18) of Group II but only 9%
      (2/22) of Group III were in sinus rhythm on follow-up. Conclusion: Device closure
      alone in patients with persistent atrial arrhythmia is not likely to restore
      sinus rhythm in the medium term. New atrial arrhythmia occurred in 6% of patients
      who were in sinus rhythm prior to device closure. At least 50% of the patients
      with paroxysmal atrial arrhythmia continue to have significant atrial arrhythmia
      following device closure, and the role of ablation prior to closure in patients
      with a history of arrhythmia requires refinement.

PMID- 27702859
TI  - Antiarrhythmic effect of vernakalant in an experimental model of Long-QT
      syndrome.
AB  - Aims: The antiarrhythmic drug vernakalant exerts antiarrhythmic effects in atrial
      fibrillation. Recent experimental data suggest interactions with the late sodium
      current and antiarrhythmic effects in ventricular arrhythmias. We aimed at
      investigating whether treatment with vernakalant reduces polymorphic ventricular
      tachycardia (VT) in an experimental model of Long-QT-syndrome (LQTS). Methods and
      results: Twenty-nine isolated rabbit hearts were assigned to two groups and
      treated with erythromycin (300 uM, n = 15) or veratridine (0.5 uM, n = 14) after
      obtaining baseline data. Thereafter, vernakalant (10 uM) was additionally
      infused. Infusion of erythromycin or veratridine significantly increased action
      potential duration (APD90) and QT interval. Erythromycin and veratridine also
      significantly augmented spatial dispersion of repolarization (erythromycin: +43
      ms; veratridine: +55 ms, P < 0.01, respectively) and temporal dispersion of
      repolarization. After lowering extracellular [K+] in bradycardic hearts, 11 of 15
      erythromycin-treated hearts and 4 of 14 veratridine-treated hearts showed early
      afterdepolarizations and subsequent polymorphic VT. Additional treatment with
      vernakalant resulted in a significant reduction of spatial dispersion of spatial
      dispersion in both groups (erythromycin: -32 ms; veratridine: -35 ms, P < 0.05
      each) and a stabilization of temporal dispersion. After additional treatment with
      vernakalant, only 5 of 15 erythromycin-treated hearts (P = 0.07) and 1 of 14
      veratridine-treated hearts (P = 0.32) presented polymorphic VT. Conclusion:
      Vernakalant has antiarrhythmic effects in this experimental model of acquired
      LQTS. A reduction of spatial dispersion of repolarization and a stabilization of
      temporal dispersion in hearts showing polymorphic VT represent the major
      underlying electrophysiological mechanisms.

PMID- 27702858
TI  - Reduction of falls and fractures after permanent pacemaker implantation in
      elderly patients with sinus node dysfunction.
AB  - Aims: Elderly patients with sinus node dysfunction (SND) are at increased risk of
      falls with possible injuries. However, the incidence of these adverse events and
      its reduction after permanent pacemaker (PPM) implantation are not known. Methods
      and results: Eighty-seven patients (mean [SD] age 75.4 [8.3] years, 51% women)
      with SND and an indication for cardiac pacing were included and were examined by
      a standardized interview targeting fall history. The incidence and total number
      of falls, falls with injury, falls requiring treatment, and falls resulting in a
      fracture were assessed for the time period of 12 months before (retrospectively)
      and after PPM implantation (prospectively). Furthermore, symptoms such as
      syncope, dizziness, and dyspnea were evaluated before and after PPM implantation.
      The implantation of a PPM was associated with a reduced proportion of patients
      experiencing at least one fall by 71% (from 53 to 15%, P < 0.001) and a reduction
      of the absolute number of falls by 90% (from 127 to 13, P < 0.001) during the 12
      months before vs. after PPM implant. Falls with injury (28 vs. 10%, P = 0.005),
      falls requiring medical attention (31 vs. 8%, P < 0.001), and falls leading to
      fracture (8 vs. 0%, P = 0.013) were similarly reduced. Notably, fewer patients
      had syncope (4 vs. 45%, P < 0.001) and dizziness after PPM implantation (12 vs.
      45%, P < 0.001). Conclusion: Falls, fall-related injuries, and fall-related
      fractures are frequent in SND patients. Permanent pacemaker implantation is
      associated with a significantly reduced risk of these adverse events, although no
      causal relationship could be established due to the study design.

PMID- 27702860
TI  - Frequent atrial extrasystolic beats predict atrial fibrillation in patients with
      congenital heart defects.
AB  - Aims: Atrial fibrillation (AF) is increasingly observed in patients with
      congenital heart defects (CHDs) who survive nowadays into adulthood. Yet,
      predictors of AF are scarce in this high-risk population. This study therefore
      examined the predictive ability of atrial extrasystole (AES) for development of
      AF in CHD patients. Methods and results: Adult CHD patients who had a 24 h Holter
      registration were followed to determine who developed AF. A total of 573 patients
      (49% male, mean age 35 +/- 12 years) were included; they had a simple/complete
      repaired CHD (n = 279), complex repaired CHD (n = 251), or univentricular heart
      (UVH, n = 43). Ageing (P < 0.0001), female gender (P = 0.028), UVH (P = 0.0010),
      and left atrial dilatation (P = 0.0025) were associated with the number of AES.
      During a median follow-up of 51.6 months (interquartile range 22.8-85.7), 29
      patients (5%) developed de novo AF. An one-point increase in the number of
      logtotal-AES was associated with a two-fold higher risk of AF development (hazard
      ratio 1.95; 95% confidence interval 1.21-3.13; P = 0.016). C-statistic for left
      atrial dilatation, complexity, and age had a good discriminative ability for the
      incidence of AF with a C-statistic of 84.5%. The addition of the total number of
      AES/24 h to this model increased C-statistic to 88.4%. Conclusion: Atrial
      extrasystole occur relatively frequent in adult CHD patients compared with
      patients with other cardiac diseases. This is the first study that showed an
      association between an increased AES frequency and a higher risk of AF
      development in CHD patients.

PMID- 27702863
TI  - The slope of the initial temperature drop predicts acute pulmonary vein isolation
      using the second-generation cryoballoon.
AB  - Aims: There is no objective, early indicator of occlusion quality, and efficacy
      of cryoballoon pulmonary vein isolation. As previous experience suggests that the
      initial cooling rate correlates with these parameters, we investigated the slope
      of the initial temperature drop as an objective measure. Methods and results: A
      systematic evaluation of 523 cryoapplications in 105 patients using a serial ROC
      AUC analysis was performed. We found the slope of a linear regression of the
      temperature-time function to be a good predictor (PPV 0.9, specificity 0.72,
      sensitivity 0.71, and ROC-AUC 0.75) of acute isolation. It also correlated with
      nadir temperatures (P< 0.001, adjusted R2= 0.43), predicted very low nadir
      temperatures, and varied according to visual occlusion grades (ANOVA P< 0.001).
      Conclusions: About 25 s after freeze initiation, the temperature-time slope
      predicts important key characteristics of a cryoablation, such as nadir
      temperature. The slope is the only reported predictor to actually precede acute
      isolation and thus to support decisions about pull-down manoeuvres or aborting a
      cryoablation early on. It is also predictive of very low nadir temperatures and
      phrenic nerve palsy and thus may add to patient safety.

PMID- 27702861
TI  - The economic impact of battery longevity in implantable cardioverter
      defibrillators for cardiac resynchronization therapy: the hospital and healthcare
      system perspectives.
AB  - Aims: Patients receiving cardiac resynchronization therapy defibrillators (CRT
      Ds) are likely to undergo one or more device replacements, mainly for battery
      depletion. We assessed the economic impact of battery depletion on the overall
      cost of CRT-D treatment from the perspectives of the healthcare system and the
      hospital. We also compared devices of different generations and from different
      manufacturers in terms of therapy cost. Methods and results: We analysed data on
      1792 CRT-Ds implanted in 1399 patients in 9 Italian centres. We calculated the
      replacement probability and the total therapy cost over 6 years, stratified by
      device generation and manufacturer. Public tariffs from diagnosis-related groups
      were used together with device prices and hospitalization costs. Generators were
      from 3 manufacturers: Boston Scientific (667, 37%), Medtronic (973, 54%), and St
      Jude Medical (152, 9%). The replacement probability at 6 years was 83 and 68% for
      earlier- and recent-generation devices, respectively. The need for replacement
      increased total therapy costs by more than 50% over the initial implantation cost
      for hospitals and by more than 30% for healthcare system. The improved longevity
      of recent-generation CRT-Ds reduced the therapy cost by ~6% in both perspectives.
      Among recent-generation CRT-Ds, the replacement probability of devices from
      different manufacturers ranged from 12 to 70%. Consequently, the maximum
      difference in therapy cost between manufacturers was 40% for hospitals and 19%
      for the healthcare system. Conclusions: Differences in CRT-D longevity strongly
      affect the overall therapy cost. While the use of recent-generation devices has
      reduced the cost, significant differences exist among currently available
      systems.

PMID- 27702864
TI  - Cryoballoon vs. radiofrequency ablation for paroxysmal atrial fibrillation: an
      updated meta-analysis of randomized and observational studies.
AB  - Aims: Radiofrequency (RF) ablation represents a standard of care for pulmonary
      vein isolation in patients with drug-refractory paroxysmal atrial fibrillation
      (AF). In this setting, cryoballoon (CB) ablation has emerged as alternative
      therapy. However, the efficacy and safety of CB vs. RF ablation in patients with
      paroxysmal AF remain a matter of debate. Methods and results: We searched
      electronic scientific databases for studies of CB vs. RF ablation in patients
      with paroxysmal AF. Aggregate data were pooled to perform a meta-analysis. The
      primary efficacy and safety outcomes were the recurrence of any atrial arrhythmia
      and procedure-related complications, respectively. A total of 6473 participants
      from 10 studies (CB, n = 2232 vs. RF, n = 4241) were studied. After a median
      follow-up of 16 months, the risk of any atrial arrhythmia recurrence (risk ratio,
      RR 95% confidence interval [95% CI] = 1.01 [0.90-1.14], P = 0.83) and procedure
      related complications (RR [95% CI] = 0.92 [0.66-1.28], P = 0.61) were comparable
      between CB vs. RF ablation. Cryoballoon ablation led to a higher risk of
      persistent phrenic nerve palsy (RR [95% CI] = 13.60 [3.87-47.81], P < 0.01) and a
      lower risk of cardiac tamponade (RR [95% CI] = 0.48 [0.25-0.89], P = 0.02)
      compared with RF ablation. There was a trend of statistically significant
      interaction between the type of CB and the duration of ablation (P for
      interaction = 0.09). Conclusion: In patients with paroxysmal AF, ablation therapy
      with CB is associated with efficacy and safety comparable to that of RF. Second
      generation CB catheters seem to reduce procedure duration. Further studies are
      warranted to disclose the impact of second-generation CB catheters compared with
      RF for ablation of paroxysmal AF.

PMID- 27702865
TI  - Atrial fibrillation detection using a novel three-vector cardiac implantable
      monitor: the atrial fibrillation detect study.
AB  - Aims: Continuous rhythm monitoring is valuable for adequate atrial fibrillation
      (AF) management in the clinical setting. Subcutaneous leadless implantable
      cardiac monitors (ICMs) yield an improved AF detection, overcoming the intrinsic
      limitations of the currently available external recording systems, thus resulting
      in a more accurate patient treatment. The study purpose was to assess the
      detection performance of a novel three-vector ICM device equipped with a
      dedicated AF algorithm. Methods and results: Sixty-six patients (86.4% males;
      mean age 60.4 +/- 9.4 years) at risk to present AF episodes, having undergone the
      novel ICM implant (BioMonitor, Biotronik SE&Co. KG, Berlin, Germany), were
      enrolled. External 48-h ECG Holter was performed 4 weeks after the device
      implantation. The automatic ICM AF classification was compared with the manual
      Holter arrhythmia recordings. Of the overall study population, 63/66 (95.5%) had
      analysable Holter data, 39/63 (62%) showed at least one true AF episode. All
      these patients had at least one AF episode stored in the ICM. On Holter
      monitoring, 24/63 (38%) patients did not show AF episodes, in 16 of them (16/24,
      67%), the ICM confirmed the absence of AF. The AF detection sensitivity and
      positive predictive value for episodes' analysis were 95.4 and 76.3%,
      respectively. Conclusion: Continuous monitoring using this novel device, equipped
      with a dedicated detection algorithm, yields an accurate and reliable detection
      of AF episodes. The ICM is a promising tool for tailoring individual AF patient
      management. Further long-term prospective studies are necessary to confirm these
      encouraging results.

PMID- 27702866
TI  - Safety and efficacy of applying a low-dose radiation fluoroscopy protocol in
      device implantations.
AB  - Aims: For cardiac implantable electronic device (CIED) implantations,
      visualization of lead placement is necessary and fluoroscopy remains by far the
      most commonly used technique. With simple changes in the X-ray system settings,
      total radiation dose can be reduced significantly. The purpose of this study was
      to assess the safety and efficacy of various CIED implantations performed after
      implementation of a new dose reduction protocol (DRP). Methods and results: We
      conducted a retrospective chart review of 584 patients undergoing CIED
      implantation or revision in our hospital. Of these patients, 280 (48%) underwent
      the implantation prior to and 304 (52%) after the DRP introduction. The DRP
      included various changes for optimized image processing and exposure system
      settings to enable dose reduction, as well as a reduced frame rates (4 FPS for
      fluoroscopy and 7.5 FPS for cinematographic images). Of the 584 patients, 53
      (9.1%) had a one-chamber pacemaker, 232 (39.7%) a two-chamber pacemaker, 133
      (22.8%) a one-chamber ICD, 35 (6.0%) a two-chamber ICD, 82 (14.0%) a CRT (de
      novo) implantation, and 49 (8.3%) had an upgrade to a CRT device. DRP was
      associated with a 64% reduction of the dose-area product (1372 +/- 2659 vs. 3792
      +/- 5025 cGcm2, P < 0.001), while fluoroscopy duration (13 +/- 15 vs. 13 +/- 15
      min) and procedural duration (93 +/- 52 vs. 92 +/- 52 min.) did not significantly
      increase. Complication rates did not differ significantly between the two groups.
      Conclusion: The DRP proved to effectively reduce radiation dose for all types of
      CIED implantations. Fluoroscopy time, total procedure time, and the number of
      complications did not increase after introducing the DRP.

PMID- 27702867
TI  - Patterns of physical activity and survival following cardiac resynchronization
      therapy implantation: the ALTITUDE activity study.
AB  - Aims: Cardiac resynchronization therapy with implantable defibrillator backup
      (CRT-D) improves outcomes, but predictors and markers of response remain limited.
      Physical activity information collected by CRT devices may provide insights to
      CRT response and the relationship between activity changes and survival. Methods
      and results: Patients entered into the LATITUDE remote monitoring system from
      2008 to 2012 after receipt of a new CRT-D were eligible. Mean daily activity was
      calculated from LATITUDE uploads at baseline (first 3-10 days following implant)
      and 6 months (180-210 days). Pairwise differences for baseline-6-month activity
      were calculated, and survival according to quintiles of 6-month activity change
      was assessed. Cox regression was used to examine the adjusted association between
      survival and baseline-6-month activity change. A total of 26 509 patients were
      followed for a median of 2.3 years (mean age 70.2 +/- 11.0 years, 70.7% male).
      Mean baseline activity was 66.2 +/- 47.7 min/day, with mean paired increase at 6
      months of 37.1 +/- 48.2 min/day [95% CI (confidence interval), 36.5-37.6, P <
      0.0001], though 15.5% of patients did not improve or worsened at 6 months.
      Survival at 3 years was significantly higher in the largest baseline-6-month
      activity change quintile vs. the lowest quintile (88.9% vs. 62.1%, log-rank P
      value < 0.001). Adjusted for age and gender, higher 6-month activity change was
      associated with a lower risk of death (adjusted hazard ratios 0.65 per 30 min
      increase in activity, 95% CI, 0.63-0.67). Conclusions: Change in physical
      activity between baseline and 6 months following CRT implantation is strongly
      associated with survival.

PMID- 27702870
TI  - Initial clinical results with the ThermoCool(r) SmartTouch(r) Surround Flow
      catheter.
AB  - Aim: The Biosense Webster ThermoCool(r) SmartTouch(r) Surround Flow (STSF)
      catheter is a recently developed ablation catheter incorporating Surround Flow
      (SF) technology to ensure efficient cooling and force sensing to quantify tissue
      contact. In our unit, it superseded the ThermoCool(r) SF catheter from the time
      of its introduction in May 2015. Methods and results: Procedure-related data were
      collected prospectively for the first 100 ablation procedures performed in our
      department using the STSF catheter. From a database of 654 procedures performed
      in our unit using the SF catheter, we selected one to match each STSF procedure,
      matching for procedure type, operator experience, patient age, and gender. The
      groups were well matched for patient age, gender, and procedure type. Procedure
      duration was similar in both groups (mean 225.5 vs. 221.4 min, IQR 106.5 vs.
      91.5, P = 0.55), but fluoroscopy duration was shorter in the STSF group (mean
      25.8 vs. 30.0, IQR 19.6 vs. 18.5, P = 0.03). No complication occurred in the STSF
      group. Complications occurred in two cases in the SF group (one pericardial
      effusion requiring drainage and one need for permanent pacing). Complete
      procedural success was achieved in 98 cases in the STSF group and 94 cases in the
      SF group (P = 0.15). The composite endpoint of procedure failure or acute
      complication was less common in the STSF group (2 vs. 8, P = 0.05). Conclusion:
      The STSF catheter is safe and effective in treating a range of arrhythmias.
      Compared with the SF catheter, it shows a trend towards improved safety-efficacy
      balance.

PMID- 27702869
TI  - Electrophysiological features and catheter ablation of symptomatic frequent
      premature atrial contractions.
AB  - Aims: Frequent premature atrial contractions (PACs) are associated with increased
      risk of atrial fibrillation (AF), stroke, and death. This study aimed to explore
      the electrophysiological features of PACs with and without inducing AF and to
      evaluate the effectiveness of catheter ablation for PACs. Methods and results:
      Thirty-five consecutive patients with symptomatic, frequent, and drug-refractory
      PACs in the absence of AF (group A) and 35 patients with PACs-induced AF (group
      B) were enrolled. Coupling intervals (CoIs) of PACs were compared. Premature
      atrial contractions were mapped by the point-by-point and/or circular mapping
      technique. Focal ablation or pulmonary vein/superior vena cava isolation was
      applied as appropriate. A total of 35 ectopic foci were identified in group A.
      The majority of them were at pulmonary vein (PV) (n = 7), crista terminalis (n =
      6), and para-Hisian area (n = 6). In group B, ectopic foci were in left-sided PVs
      in 21 patients, in right-sided PVs in 13 patients, and in SVC in 1 patient. There
      was significant difference in CoIs of PACs triggering AF and those from PVs and
      non-PV areas but without causing AF (362.8 +/- 23.0 ms vs. 470.6 +/- 60.1 ms vs.
      515.6 +/- 77.2 ms, P< 0.001). Premature atrial contractions were abolished in 32
      of 35 patients from group A and in all patients from group B. At the end of
      follow-up, 29 patients in group A and 28 patients in group B were free of
      recurrence (off antiarrhythmic drugs) after the initial ablation (P =0.97).
      Conclusions: Frequent PACs in the absence of AF were characterized as having
      their predilection sites and longer CoIs than those inducing AF. Catheter
      ablation was effective to eliminate symptomatic, frequent, and drug-refractory
      PACs.

PMID- 27702871
TI  - Impact of concomitant atrial fibrillation on the prognosis of Takotsubo
      cardiomyopathy.
AB  - Aims: Previous studies revealed that patients with Takotsubo cardiomyopathy (TTC)
      have a higher mortality rate than the general population. Supraventricular
      tachycardia is a well-known complication of TTC. This study was performed to
      determine the short- and long-term prognostic impact of atrial fibrillation
      associated with TTC patients. Methods and results: Our institutional database
      constituted a collective of 114 patients diagnosed with TTC from 2003 to 2015.
      The patients were divided into two groups according to the presence (n = 21,
      18.4%) or absence (n = 93, 81.5%) of atrial fibrillation. The endpoint was a
      composite of in-hospital events (thromboembolic events and life-threatening
      arrhythmias), all-cause mortality, rehospitalization due to heart failure,
      stroke, and the recurrence of TTC. The in-hospital mortality, 30-day mortality,
      and long-term mortality were significantly higher in the atrial fibrillation
      group. Kaplan-Meier analysis indicated a significantly lower event-free survival
      rate over a mean follow-up of 3 years in the atrial fibrillation group than that
      in the non-atrial fibrillation group (log-rank, P < 0.01). In a multivariate cox
      regression analysis, atrial fibrillation (hazard ratio, HR 2.3, 95% confidence
      interval, CI: 1.1-4.9, P < 0.05) and EF <= 35% (HR 2.0, 95% CI: 1.1-3.8, P <
      0.05) were the only independent predictors of a primary endpoint. Conclusion:
      Rates of in-hospital events and short- as well as long-term mortality were
      significantly higher in TTC patients suffering from atrial fibrillation compared
      with patients without atrial fibrillation.

PMID- 27702872
TI  - Study on the influence of oxidative stress on the fibrillization of fibrinogen.
AB  - Human fibrinogen is an important coagulation factor as well as an independent
      predictor of coronary heart disease and stroke. Analysis of dysfibrinogens may
      provide useful information and help us to understand the molecular defects in
      fibrin polymerization. In the present study, we investigated the influence of
      oxidative stress of fibrinogen induced by H2O2 on the polymerization state of
      fibrin. UV absorbance spectroscopy, circular dichroism, zeta-potential, dynamic
      light scattering and steady shear viscosity were all employed to study the
      influence of oxidative stress on the molecular structure, the surface charges,
      and the size and shape of fibrinogen molecules. The fibrin morphology obtained
      was imaged and investigated using atomic force microscopy. The results
      demonstrated that the cross-linking, branching and height distribution of formed
      fibrin will be influenced by the oxidative stress of fibrinogen. This study
      presents new insights into the aggregation behaviour of fibrinogen and will be
      helpful to understand the formation mechanism of thrombosis under oxidative
      stress.

PMID- 27702873
TI  - Science and Culture: Petri palettes create microbial masterpieces.

PMID- 27702874
TI  - Core Concept: The Internet of Things and the explosion of interconnectivity.

PMID- 27702876
TI  - Consideration of cognitive variance components potentially solves Beauchamp's
      paradox.

PMID- 27702877
TI  - Reply to Woodley of Menie: Natural selection, educational attainment, and
      cognitive variance components.

PMID- 27702878
TI  - Functional assessment of cerebral artery stenosis: A pilot study based on
      computational fluid dynamics.
AB  - The fractional pressure ratio is introduced to quantitatively assess the
      hemodynamic significance of severe intracranial stenosis. A computational fluid
      dynamics-based method is proposed to non-invasively compute the FPRCFD and
      compared against fractional pressure ratio measured by an invasive technique.
      Eleven patients with severe intracranial stenosis considered for endovascular
      intervention were recruited and an invasive procedure was performed to measure
      the distal and the aortic pressure ( Pd and Pa). The fractional pressure ratio
      was calculated as [Formula: see text]. The computed tomography angiography was
      used to reconstruct three-dimensional (3D) arteries for each patient. Cerebral
      hemodynamics was then computed for the arteries using a mathematical model
      governed by Navier-Stokes equations and with the outflow conditions imposed by a
      model of distal resistance and compliance. The non-invasive [Formula: see text],
      [Formula: see text], and FPRCFD were then obtained from the computational fluid
      dynamics calculation using a 16-core parallel computer. The invasive and non
      invasive parameters were tested by statistical analysis. For this group of
      patients, the computational fluid dynamics method achieved comparable results
      with the invasive measurements. The fractional pressure ratio and FPRCFD are very
      close and highly correlated, but not linearly proportional, with the percentage
      of stenosis. The proposed computational fluid dynamics method can potentially be
      useful in assessing the functional alteration of cerebral stenosis.

PMID- 27702879
TI  - Pulsatility and high shear stress deteriorate barrier phenotype in brain
      microvascular endothelium.
AB  - Microvascular endothelial cells at the blood-brain barrier exhibit a protective
      phenotype, which is highly induced by biochemical and biomechanical stimuli.
      Amongst them, shear stress enhances junctional tightness and limits transport at
      capillary-like levels. Abnormal flow patterns can reduce functional features of
      macrovascular endothelium. We now examine if this is true in brain microvascular
      endothelial cells. We suggest in this paper a complex response of endothelial
      cells to aberrant forces under different flow domains. Human brain microvascular
      endothelial cells were exposed to physiological or abnormal flow patterns.
      Physiologic shear (10-20 dyn/cm2) upregulates expression of tight junction
      markers Zona Occludens 1 (1.7-fold) and Claudin-5 (more than 2-fold). High shear
      stress (40 dyn/cm2) and/or pulsatility decreased their expression to basal levels
      and altered junctional morphology. We exposed cells to pathological shear stress
      patterns followed by capillary-like conditions. Results showed reversible
      recovery on the expression of tight junction markers. Flow protection of barrier
      phenotype commensurate with junctional signaling pathways decrease (Src, 0.25
      fold, ERK, 0.77-fold) when compared to static conditions. This decrease was lost
      under high shear and pulsatile flow. In conclusion, abnormal shear stress
      inherent to systemic vascular disease leads to barrier impairment, which could be
      reverted by hemodynamic interventions.

PMID- 27702880
TI  - Imaging of brain oxygenation with magnetic resonance imaging: A validation with
      positron emission tomography in the healthy and tumoural brain.
AB  - The partial pressure in oxygen remains challenging to map in the brain. Two main
      strategies exist to obtain surrogate measures of tissue oxygenation: the tissue
      saturation studied by magnetic resonance imaging (StO2-MRI) and the
      identification of hypoxia by a positron emission tomography (PET) biomarker with
      3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]-FMISO) as the leading
      radiopharmaceutical. Nonetheless, a formal validation of StO2-MRI against FMISO
      PET has not been performed. The objective of our studies was to compare the two
      approaches in (a) the normal rat brain when the rats were submitted to hypoxemia;
      (b) animals implanted with four tumour types differentiated by their oxygenation.
      Rats were submitted to normoxic and hypoxemic conditions. For the brain tumour
      experiments, U87-MG, U251-MG, 9L and C6 glioma cells were orthotopically
      inoculated in rats. For both experiments, StO2-MRI and [18F]-FMISO PET were
      performed sequentially. Under hypoxemia conditions, StO2-MRI revealed a decrease
      in oxygen saturation in the brain. Nonetheless, [18F]-FMISO PET, pimonidazole
      immunohistochemistry and molecular biology were insensitive to hypoxia. Within
      the context of tumours, StO2-MRI was able to detect hypoxia in the hypoxic
      models, mimicking [18F]-FMISO PET with high sensitivity/specificity. Altogether,
      our data clearly support that, in brain pathologies, StO2-MRI could be a robust
      and specific imaging biomarker to assess hypoxia.

PMID- 27702881
TI  - Minimally invasive beat-by-beat monitoring of cardiac power in normal hearts and
      during acute ventricular dysfunction.
AB  - Cardiac power, the product of aortic flow and blood pressure, appears to be a
      fundamental cardiovascular parameter. The simplified version named cardiac power
      output (CPO), calculated as the product of cardiac output (CO) in L/min and mean
      arterial pressure (MAP) in mmHg divided by 451, has shown great ability to
      predict outcome in a broad spectrum of cardiac disease. Beat-by-beat evaluation
      of cardiac power (PWR) therefore appears to be a possibly valuable addition when
      monitoring circulatory unstable patients, providing parameters of overall
      cardiovascular function. We have developed a minimally invasive system for
      cardiac power measurement, and aimed in this study to compare this system to an
      invasive method (ttPWR). Seven male anesthetized farm pigs were included. A
      laptop with in-house software gathered audio from Doppler signals of aortic flow
      and blood pressure from the patient monitor to continuously calculate and display
      a minimally invasive cardiac power trace (uPWR). The time integral per cardiac
      cycle (uPWR-integral) represents cardiac work, and was compared to the invasive
      counterpart (ttPWR-integral). Signals were obtained at baseline, during
      mechanically manipulated preload and afterload, before and after induced global
      ischemic left ventricular dysfunction. We found that the uPWR-integral
      overestimated compared to the ttPWR-integral by about 10% (P < 0.001) in both
      normal hearts and during ventricular dysfunction. Bland-Altman limits of
      agreement were at +0.060 and -0.054 J, without increasing spread over the range.
      In conclusion we find that the minimally invasive system follows its invasive
      counterpart, and is ready for clinical research of cardiac power parameters.

PMID- 27702882
TI  - Ischemia/reperfusion-induced alterations of enzymatic and signaling functions of
      the rat cardiac Na+/K+-ATPase: protection by ouabain preconditioning.
AB  - Cardiac glycosides (CG) are traditionally known as positive cardiac inotropes
      that inhibit Na+/K+-ATPase-dependent ion transport. CG also trigger-specific
      signaling pathways through the cardiac Na+/K+-ATPase, with beneficial effects in
      ischemia/reperfusion (I/R) injury (e.g., ouabain preconditioning, known as OPC)
      and hypertrophy. Our current understanding of hypersensitivity to CG and
      subsequent toxicity in the ischemic heart is mostly based on specific I/R-induced
      alterations of the Na+/K+-ATPase enzymatic function and has remained incomplete.
      The primary goal of this study was to investigate and compare the impact of I/R
      on Na+/K+-ATPase enzymatic and signaling functions. Second, we assessed the
      impact of OPC on both functions. Langendorff-perfused rat hearts were exposed to
      30 min of ischemia and 30 min of reperfusion. At the inotropic concentration of
      50 MUmol/L, ouabain increased ERK and Akt phosphorylation in control hearts. In
      I/R hearts, this concentration did not induced positive inotropy and failed to
      induce Akt or ERK phosphorylation. The inotropic response to dobutamine as well
      as insulin signaling persisted, suggesting specific alterations of Na+/K+-ATPase.
      Indeed, Na+/K+-ATPase protein expression was intact, but the enzyme activity was
      decreased by 60% and the enzymatic function of the isoform with high affinity for
      ouabain was abolished following I/R. Strikingly, OPC prevented all I/R-induced
      alterations of the receptor. Further studies are needed to reveal the respective
      roles of I/R-induced modulations of Na+/K+-ATPase enzymatic and signaling
      functions in cardiomyocyte death.

PMID- 27702883
TI  - Internal carotid artery blood flow in healthy awake subjects is reduced by
      simulated hypovolemia and noninvasive mechanical ventilation.
AB  - Intact cerebral blood flow (CBF) is essential for cerebral metabolism and
      function, whereas hypoperfusion in relation to hypovolemia and hypocapnia can
      lead to severe cerebral damage. This study was designed to assess internal
      carotid artery blood flow (ICA-BF) during simulated hypovolemia and noninvasive
      positive pressure ventilation (PPV) in young healthy humans. Beat-by-beat blood
      velocity (ICA and aorta) were measured by Doppler ultrasound during normovolemia
      and simulated hypovolemia (lower body negative pressure), with or without PPV in
      15 awake subjects. Heart rate, plethysmographic finger arterial pressure,
      respiratory frequency, and end-tidal CO2 (ETCO2) were also recorded. Cardiac
      index (CI) and ICA-BF were calculated beat-by-beat. Medians and 95% confidence
      intervals and Wilcoxon signed rank test for paired samples were used to test the
      difference between conditions. Effects on ICA-BF were modeled by linear mixed
      effects regression analysis. During spontaneous breathing, ICA-BF was reduced
      from normovolemia (247, 202-284 mL/min) to hypovolemia (218, 194-271 mL/min).
      During combined PPV and hypovolemia, ICA-BF decreased by 15% (200, 152-231
      mL/min, P = 0.001). Regression analysis attributed this fall to concurrent
      reductions in CI (beta: 43.2, SE: 17.1, P = 0.013) and ETCO2 (beta: 32.8, SE:
      9.3, P = 0.001). Mean arterial pressure was maintained and did not contribute to
      ICA-BF variance. In healthy awake subjects, ICA-BF was significantly reduced
      during simulated hypovolemia combined with noninvasive PPV Reductions in CI and
      ETCO2 had additive effects on ICA-BF reduction. In hypovolemic patients, even low
      pressure noninvasive ventilation may cause clinically relevant reductions in CBF,
      despite maintained arterial blood pressure.

PMID- 27702885
TI  - Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to
      pressure overload.
AB  - Pathological cardiac hypertrophy is an independent risk factor of heart failure.
      However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12
      is a member of the dual specific phosphatase (DUSP) family, which is
      characterized by its DUSP activity to dephosphorylate both tyrosine and
      serine/threonine residues on one substrate. Some DUSPs have been identified as
      being involved in the regulation of cardiac hypertrophy. However, the role of
      DUSP12 during pathological cardiac hypertrophy is still unclear. In the present
      study, we observed a significant decrease in DUSP12 expression in hypertrophic
      hearts and cardiomyocytes. Using a genetic loss-of-function murine model, we
      demonstrated that DUSP12 deficiency apparently aggravated pressure overload
      induced cardiac hypertrophy and fibrosis as well as impaired cardiac function,
      whereas cardiac-specific overexpression of DUPS12 was capable of reversing this
      hypertrophic and fibrotic phenotype and improving contractile function.
      Furthermore, we demonstrated that JNK1/2 activity but neither ERK1/2 nor p38
      activity was increased in the DUSP12 deficient group and decreased in the DUSP12
      overexpression group both in vitro and in vivo under hypertrophic stress
      conditions. Pharmacological inhibition of JNK1/2 activity (SP600125) is capable
      of reversing the hypertrophic phenotype in DUSP12 knockout (KO) mice. DUSP12
      protects against pathological cardiac hypertrophy and related pathologies. This
      regulatory role of DUSP12 is primarily through c-Jun N-terminal kinase (JNK)
      inhibition. DUSP12 could be a promising therapeutic target of pathological
      cardiac hypertrophy. DUSP12 is down-regulated in hypertrophic hearts. An absence
      of DUSP12 aggravated cardiac hypertrophy, whereas cardiomyocyte-specific DUSP12
      overexpression can alleviate this hypertrophic phenotype with improved cardiac
      function. Further study demonstrated that DUSP12 inhibited JNK activity to
      attenuate pathological cardiac hypertrophy.

PMID- 27702884
TI  - Retino-cortical stimulus frequency-dependent gamma coupling: evidence and
      functional implications of oscillatory potentials.
AB  - Long-range gamma band EEG oscillations mediate information transmission between
      distant brain regions. Gamma band-based coupling may not be restricted to cortex
      to-cortex communication but may include extracortical parts of the visual system.
      The retinogram and visual event-related evoked potentials exhibit time-locked,
      forward propagating oscillations that are candidates of gamma oscillatory
      coupling between the retina and the visual cortex. In this study, we tested if
      this gamma coupling is present as indicated by the coherence of gamma-range (70
      200 Hz) oscillatory potentials (OPs) recorded simultaneously from the retina and
      the primary visual cortex in freely moving, adult rats. We found significant
      retino-cortical OP coherence in a wide range of stimulus duration (0.01-1000
      msec), stimulus intensity (800-5000 mcd/mm2), interstimulus interval (10-400
      msec), and stimulus frequency (0.25-25 Hz). However, at low stimulus frequencies,
      the OPs were time-locked, flickering light at 25 Hz entrained continuous OP
      coherence (steady-state response, SSR). Our results suggest that the retina and
      the visual cortex exhibit oscillatory coupling at high-gamma frequency with
      precise time locking and synchronization of information transfer from the retina
      to the visual cortex, similar to cortico-cortical gamma coupling. The temporal
      fusion of retino-cortical gamma coherence at stimulus rates of theater movies may
      explain the mechanism of the visual illusion of continuity. How visual perception
      depends on early transformations of ascending sensory information is incompletely
      understood. By simultaneous measurement of flash-evoked potentials in the retina
      and the visual cortex in awake, freely moving rats, we demonstrate for the first
      time that time-locked gamma oscillatory potentials exhibit stable retino-cortical
      synchrony across a wide range of stimulus parameters and that the temporal
      continuity of coherence changes with stimulus frequency according to the expected
      change in the visual illusion of continuity.

PMID- 27702886
TI  - "So Much of This Story Could Be Me": Men's Use of Support in Online Infertility
      Discussion Boards.
AB  - Past research has suggested that social support can reduce the negative
      psychological consequences associated with infertility. Online discussion boards
      (ODBs) appear to be a novel and valuable venue for men with fertility problems to
      acquire support from similar others. Research has not employed a social support
      framework to classify the types of support men are offered and receive. Using
      template, content, and thematic analysis, this study sought to identify what
      types of social support men seek and receive on online infertility discussion
      boards while exploring how men having fertility problems use appraisal support to
      assist other men. One hundred and ninety-nine unique users were identified on two
      online infertility discussion boards. Four types of social support (appraisal,
      emotional, informational, and instrumental) were evident on ODBs, with appraisal
      support (36%) being used most often to support other men. Within appraisal
      support, five themes were identified that showed how men communicate this type of
      support to assist other men: "At the end of the day, we're all emotionally
      exhausted"; "So much of this could be me, infertility happens more than you
      think"; "I've also felt like the worst husband in the world"; "It's just
      something that nobody ever talks about so it's really shocking to hear"; "I say
      this as a man, you're typing my thoughts exactly." These findings confirm how
      ODBs can be used as a potential medium to expand one's social network and acquire
      support from people who have had a similar experience.

PMID- 27702887
TI  - Don't Change Much.
AB  - Few studies have assessed differences in the prevalence of and economic burden
      attributable to tobacco smoking, excess weight, physical inactivity, and alcohol
      use by gender. This article examines these gender differences in Canadians
      between the ages of 30 and 64 years. It also estimates the potential cost
      avoidance if the prevalence of the four risk factors (RFs) were reduced modestly
      in males. Data on the prevalence of the RFs and the relative risk of disease
      associated with each of the RFs were combined to calculate population
      attributable fractions. A prevalence-based cost-of-illness approach was used to
      estimate the economic burden associated with the four RFs. Middle-aged Canadian
      males are more likely to smoke tobacco (26.4% vs. 20.2%), consume hazardous or
      harmful levels of alcohol (14.6% vs. 8.2%), and have excess weight (65.6% vs.
      47.1%) than middle-aged Canadian females, resulting in an annual economic burden
      that is 27% higher in males than females. No significant differences were
      observed in the proportion of males who are physically inactive (48.4% vs.
      49.4%). Modelling only a 1% annual relative reduction each year through to 2036
      would result in a cumulative cost avoidance between 2013 and 2036 of $50.7
      billion. The differences in RF prevalence between middle-aged males and females
      have an important effect on the population's economic burden. A modest annual
      reduction in the four RFs in males can significantly affect population health and
      the economy over time.

PMID- 27702888
TI  - Deep sequencing of 10,000 human genomes.
AB  - We report on the sequencing of 10,545 human genomes at 30*-40* coverage with an
      emphasis on quality metrics and novel variant and sequence discovery. We find
      that 84% of an individual human genome can be sequenced confidently. This high
      confidence region includes 91.5% of exon sequence and 95.2% of known pathogenic
      variant positions. We present the distribution of over 150 million single
      nucleotide variants in the coding and noncoding genome. Each newly sequenced
      genome contributes an average of 8,579 novel variants. In addition, each genome
      carries on average 0.7 Mb of sequence that is not found in the main build of the
      hg38 reference genome. The density of this catalog of variation allowed us to
      construct high-resolution profiles that define genomic sites that are highly
      intolerant of genetic variation. These results indicate that the data generated
      by deep genome sequencing is of the quality necessary for clinical use.

PMID- 27702889
TI  - Black carbon solar absorption suppresses turbulence in the atmospheric boundary
      layer.
AB  - The introduction of cloud condensation nuclei and radiative heating by sunlight
      absorbing aerosols can modify the thickness and coverage of low clouds, yielding
      significant radiative forcing of climate. The magnitude and sign of changes in
      cloud coverage and depth in response to changing aerosols are impacted by
      turbulent dynamics of the cloudy atmosphere, but integrated measurements of
      aerosol solar absorption and turbulent fluxes have not been reported thus far.
      Here we report such integrated measurements made from unmanned aerial vehicles
      (UAVs) during the CARDEX (Cloud Aerosol Radiative Forcing and Dynamics
      Experiment) investigation conducted over the northern Indian Ocean. The UAV and
      surface data reveal a reduction in turbulent kinetic energy in the surface mixed
      layer at the base of the atmosphere concurrent with an increase in absorbing
      black carbon aerosols. Polluted conditions coincide with a warmer and shallower
      surface mixed layer because of aerosol radiative heating and reduced turbulence.
      The polluted surface mixed layer was also observed to be more humid with higher
      relative humidity. Greater humidity enhances cloud development, as evidenced by
      polluted clouds that penetrate higher above the top of the surface mixed layer.
      Reduced entrainment of dry air into the surface layer from above the inversion
      capping the surface mixed layer, due to weaker turbulence, may contribute to
      higher relative humidity in the surface layer during polluted conditions.
      Measurements of turbulence are important for studies of aerosol effects on
      clouds. Moreover, reduced turbulence can exacerbate both the human health impacts
      of high concentrations of fine particles and conditions favorable for low
      visibility fog events.

PMID- 27702892
TI  - Predictability and hierarchy in Drosophila behavior.
AB  - Even the simplest of animals exhibit behavioral sequences with complex temporal
      dynamics. Prominent among the proposed organizing principles for these dynamics
      has been the idea of a hierarchy, wherein the movements an animal makes can be
      understood as a set of nested subclusters. Although this type of organization
      holds potential advantages in terms of motion control and neural circuitry,
      measurements demonstrating this for an animal's entire behavioral repertoire have
      been limited in scope and temporal complexity. Here, we use a recently developed
      unsupervised technique to discover and track the occurrence of all stereotyped
      behaviors performed by fruit flies moving in a shallow arena. Calculating the
      optimally predictive representation of the fly's future behaviors, we show that
      fly behavior exhibits multiple time scales and is organized into a hierarchical
      structure that is indicative of its underlying behavioral programs and its
      changing internal states.

PMID- 27702893
TI  - Designer shocks for carving out microscale surface morphologies.

PMID- 27702890
TI  - Hypoxia-activated cytotoxic agent tirapazamine enhances hepatic artery ligation
      induced killing of liver tumor in HBx transgenic mice.
AB  - Transarterial chemoembolization (TACE) is the main treatment for intermediate
      stage hepatocellular carcinoma (HCC) with Barcelona Clinic Liver Cancer
      classification because of its exclusive arterial blood supply. Although TACE
      achieves substantial necrosis of the tumor, complete tumor necrosis is uncommon,
      and the residual tumor generally rapidly recurs. We combined tirapazamine (TPZ),
      a hypoxia-activated cytotoxic agent, with hepatic artery ligation (HAL), which
      recapitulates transarterial embolization in mouse models, to enhance the efficacy
      of TACE. The effectiveness of this combination treatment was examined in HCC that
      spontaneously developed in hepatitis B virus X protein (HBx) transgenic mice. We
      proved that the tumor blood flow in this model was exclusively supplied by the
      hepatic artery, in contrast to conventional orthotopic HCC xenografts that
      receive both arterial and venous blood supplies. At levels below the threshold
      oxygen levels created by HAL, TPZ was activated and killed the hypoxic cells, but
      spared the normoxic cells. This combination treatment clearly limited the
      toxicity of TPZ to HCC, which caused the rapid and near-complete necrosis of HCC.
      In conclusion, the combination of TPZ and HAL showed a synergistic tumor killing
      activity that was specific for HCC in HBx transgenic mice. This preclinical study
      forms the basis for the ongoing clinical program for the TPZ-TACE regimen in HCC
      treatment.

PMID- 27702891
TI  - Label-free imaging of the native, living cellular nanoarchitecture using partial
      wave spectroscopic microscopy.
AB  - The organization of chromatin is a regulator of molecular processes including
      transcription, replication, and DNA repair. The structures within chromatin that
      regulate these processes span from the nucleosomal (10-nm) to the chromosomal
      (>200-nm) levels, with little known about the dynamics of chromatin structure
      between these scales due to a lack of quantitative imaging technique in live
      cells. Previous work using partial-wave spectroscopic (PWS) microscopy, a
      quantitative imaging technique with sensitivity to macromolecular organization
      between 20 and 200 nm, has shown that transformation of chromatin at these length
      scales is a fundamental event during carcinogenesis. As the dynamics of chromatin
      likely play a critical regulatory role in cellular function, it is critical to
      develop live-cell imaging techniques that can probe the real-time temporal
      behavior of the chromatin nanoarchitecture. Therefore, we developed a live-cell
      PWS technique that allows high-throughput, label-free study of the causal
      relationship between nanoscale organization and molecular function in real time.
      In this work, we use live-cell PWS to study the change in chromatin structure due
      to DNA damage and expand on the link between metabolic function and the structure
      of higher-order chromatin. In particular, we studied the temporal changes to
      chromatin during UV light exposure, show that live-cell DNA-binding dyes induce
      damage to chromatin within seconds, and demonstrate a direct link between higher
      order chromatin structure and mitochondrial membrane potential. Because
      biological function is tightly paired with structure, live-cell PWS is a powerful
      tool to study the nanoscale structure-function relationship in live cells.

PMID- 27702894
TI  - Energy-efficient neural network chips approach human recognition capabilities.

PMID- 27702895
TI  - Sustained antigen availability during germinal center initiation enhances
      antibody responses to vaccination.
AB  - Natural infections expose the immune system to escalating antigen and
      inflammation over days to weeks, whereas nonlive vaccines are single bolus
      events. We explored whether the immune system responds optimally to antigen
      kinetics most similar to replicating infections, rather than a bolus dose. Using
      HIV antigens, we found that administering a given total dose of antigen and
      adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced
      humoral responses, with exponentially increasing (exp-inc) dosing profiles
      eliciting >10-fold increases in antibody production relative to bolus vaccination
      post prime. Computational modeling of the germinal center response suggested that
      antigen availability as higher-affinity antibodies evolve enhances antigen
      capture in lymph nodes. Consistent with these predictions, we found that exp-inc
      dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell
      and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant
      kinetics may enable increased vaccine potency.

PMID- 27702896
TI  - Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse
      models of lung adenocarcinoma.
AB  - Genetically engineered mouse models (GEMMs) of cancer are increasingly being used
      to assess putative driver mutations identified by large-scale sequencing of human
      cancer genomes. To accurately interpret experiments that introduce additional
      mutations, an understanding of the somatic genetic profile and evolution of GEMM
      tumors is necessary. Here, we performed whole-exome sequencing of tumors from
      three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor
      receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or
      overexpression of MYC proto-oncogene. Tumors from EGFR- and Kras-driven models
      exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a
      dramatically lower average mutational frequency than observed in human lung
      adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR
      and Kras) harbored few mutations in known cancer genes, whereas tumors driven by
      MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal
      oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both
      exhibited recurrent whole-chromosome DNA copy number alterations, the specific
      chromosomes altered by gain or loss were different in each model. These data
      demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared
      with human cancers of a similar type, making these autochthonous model systems
      useful for additive engineering approaches to assess the potential of novel
      mutations on tumorigenesis, cancer progression, and drug sensitivity.

PMID- 27702897
TI  - Real-time analysis of RAG complex activity in V(D)J recombination.
AB  - Single-molecule FRET (smFRET) and single-molecule colocalization (smCL) assays
      have allowed us to observe the recombination-activating gene (RAG) complex
      reaction mechanism in real time. Our smFRET data have revealed distinct bending
      modes at recombination signal sequence (RSS)-conserved regions before nicking and
      synapsis. We show that high mobility group box 1 (HMGB1) acts as a cofactor in
      stabilizing conformational changes at the 12RSS heptamer and increasing RAG1/2
      binding affinity for 23RSS. Using smCL analysis, we have quantitatively measured
      RAG1/2 dwell time on 12RSS, 23RSS, and non-RSS DNA, confirming a strict RSS
      molecular specificity that was enhanced in the presence of a partner RSS in
      solution. Our studies also provide single-molecule determination of rate
      constants that were previously only possible by indirect methods, allowing us to
      conclude that RAG binding, bending, and synapsis precede catalysis. Our real-time
      analysis offers insight into the requirements for RSS-RSS pairing, architecture
      of the synaptic complex, and dynamics of the paired RSS substrates. We show that
      the synaptic complex is extremely stable and that heptamer regions of the 12RSS
      and 23RSS substrates in the synaptic complex are closely associated in a stable
      conformational state, whereas nonamer regions are perpendicular. Our data provide
      an enhanced and comprehensive mechanistic description of the structural dynamics
      and associated enzyme kinetics of variable, diversity, and joining [V(D)J]
      recombination.

PMID- 27702898
TI  - Decay of an active GPCR: Conformational dynamics govern agonist rebinding and
      persistence of an active, yet empty, receptor state.
AB  - Here, we describe two insights into the role of receptor conformational dynamics
      during agonist release (all-trans retinal, ATR) from the visual G protein-coupled
      receptor (GPCR) rhodopsin. First, we show that, after light activation, ATR can
      continually release and rebind to any receptor remaining in an active-like
      conformation. As with other GPCRs, we observe that this equilibrium can be
      shifted by either promoting the active-like population or increasing the agonist
      concentration. Second, we find that during decay of the signaling state an active
      like, yet empty, receptor conformation can transiently persist after retinal
      release, before the receptor ultimately collapses into an inactive conformation.
      The latter conclusion is based on time-resolved, site-directed fluorescence
      labeling experiments that show a small, but reproducible, lag between the retinal
      leaving the protein and return of transmembrane helix 6 (TM6) to the inactive
      conformation, as determined from tryptophan-induced quenching studies.
      Accelerating Schiff base hydrolysis and subsequent ATR dissociation, either by
      addition of hydroxylamine or introduction of mutations, further increased the
      time lag between ATR release and TM6 movement. These observations show that
      rhodopsin can bind its agonist in equilibrium like a traditional GPCR, provide
      evidence that an active GPCR conformation can persist even after agonist release,
      and raise the possibility of targeting this key photoreceptor protein by
      traditional pharmaceutical-based treatments.

PMID- 27702900
TI  - Architecture of a minimal signaling pathway explains the T-cell response to a 1
      million-fold variation in antigen affinity and dose.
AB  - T cells must respond differently to antigens of varying affinity presented at
      different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell
      responses have produced inconsistent patterns of responses, preventing
      formulations of canonical models of T-cell signaling. Here, a systematic analysis
      of T-cell responses to 1 million-fold variations in both pMHC affinity and dose
      produced bell-shaped dose-response curves and different optimal pMHC affinities
      at different pMHC doses. Using sequential model rejection/identification
      algorithms, we identified a unique, minimal model of cellular signaling
      incorporating kinetic proofreading with limited signaling coupled to an
      incoherent feed-forward loop (KPL-IFF) that reproduces these observations. We
      show that the KPL-IFF model correctly predicts the T-cell response to antigen
      copresentation. Our work offers a general approach for studying cellular
      signaling that does not require full details of biochemical pathways.

PMID- 27702902
TI  - Isotopic overprinting of nitrification on denitrification as a ubiquitous and
      unifying feature of environmental nitrogen cycling.
AB  - Natural abundance nitrogen and oxygen isotopes of nitrate (delta15NNO3 and
      delta18ONO3) provide an important tool for evaluating sources and transformations
      of natural and contaminant nitrate (NO3-) in the environment. Nevertheless,
      conventional interpretations of NO3- isotope distributions appear at odds with
      patterns emerging from studies of nitrifying and denitrifying bacterial cultures.
      To resolve this conundrum, we present results from a numerical model of NO3-
      isotope dynamics, demonstrating that deviations in delta18ONO3 vs. delta15NNO3
      from a trajectory of 1 expected for denitrification are explained by isotopic
      over-printing from coincident NO3- production by nitrification and/or anammox.
      The analysis highlights two driving parameters: (i) the delta18O of ambient water
      and (ii) the relative flux of NO3- production under net denitrifying conditions,
      whether catalyzed aerobically or anaerobically. In agreement with existing
      analyses, dual isotopic trajectories >1, characteristic of marine denitrifying
      systems, arise predominantly under elevated rates of NO2- reoxidation relative to
      NO3- reduction (>50%) and in association with the elevated delta18O of seawater.
      This result specifically implicates aerobic nitrification as the dominant NO3-
      producing term in marine denitrifying systems, as stoichiometric constraints
      indicate anammox-based NO3- production cannot account for trajectories >1. In
      contrast, trajectories <1 comprise the majority of model solutions, with those
      representative of aquifer conditions requiring lower NO2- reoxidation fluxes
      (<15%) and the influence of the lower delta18O of freshwater. Accordingly, we
      suggest that widely observed delta18ONO3 vs. delta15NNO3 trends in freshwater
      systems (<1) must result from concurrent NO3- production by anammox in anoxic
      aquifers, a process that has been largely overlooked.

PMID- 27702901
TI  - Allelic barley MLA immune receptors recognize sequence-unrelated avirulence
      effectors of the powdery mildew pathogen.
AB  - Disease-resistance genes encoding intracellular nucleotide-binding domain and
      leucine-rich repeat proteins (NLRs) are key components of the plant innate immune
      system and typically detect the presence of isolate-specific avirulence (AVR)
      effectors from pathogens. NLR genes define the fastest-evolving gene family of
      flowering plants and are often arranged in gene clusters containing multiple
      paralogs, contributing to copy number and allele-specific NLR variation within a
      host species. Barley mildew resistance locus a (Mla) has been subject to
      extensive functional diversification, resulting in allelic resistance
      specificities each recognizing a cognate, but largely unidentified, AVRa gene of
      the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh). We applied a
      transcriptome-wide association study among 17 Bgh isolates containing different
      AVRa genes and identified AVRa1 and AVRa13, encoding candidate-secreted effectors
      recognized by Mla1 and Mla13 alleles, respectively. Transient expression of the
      effector genes in barley leaves or protoplasts was sufficient to trigger Mla1 or
      Mla13 allele-specific cell death, a hallmark of NLR receptor-mediated immunity.
      AVRa1 and AVRa13 are phylogenetically unrelated, demonstrating that certain
      allelic MLA receptors evolved to recognize sequence-unrelated effectors. They are
      ancient effectors because corresponding loci are present in wheat powdery mildew.
      AVRA1 recognition by barley MLA1 is retained in transgenic Arabidopsis,
      indicating that AVRA1 directly binds MLA1 or that its recognition involves an
      evolutionarily conserved host target of AVRA1 Furthermore, analysis of
      transcriptome-wide sequence variation among the Bgh isolates provides evidence
      for Bgh population structure that is partially linked to geographic isolation.

PMID- 27702903
TI  - Nonlinear two-dimensional terahertz photon echo and rotational spectroscopy in
      the gas phase.
AB  - Ultrafast 2D spectroscopy uses correlated multiple light-matter interactions for
      retrieving dynamic features that may otherwise be hidden under the linear
      spectrum; its extension to the terahertz regime of the electromagnetic spectrum,
      where a rich variety of material degrees of freedom reside, remains an
      experimental challenge. We report a demonstration of ultrafast 2D terahertz
      spectroscopy of gas-phase molecular rotors at room temperature. Using time
      delayed terahertz pulse pairs, we observe photon echoes and other nonlinear
      signals resulting from molecular dipole orientation induced by multiple terahertz
      field-dipole interactions. The nonlinear time domain orientation signals are
      mapped into the frequency domain in 2D rotational spectra that reveal J-state
      resolved nonlinear rotational dynamics. The approach enables direct observation
      of correlated rotational transitions and may reveal rotational coupling and
      relaxation pathways in the ground electronic and vibrational state.

PMID- 27702904
TI  - Theory of prokaryotic genome evolution.
AB  - Bacteria and archaea typically possess small genomes that are tightly packed with
      protein-coding genes. The compactness of prokaryotic genomes is commonly
      perceived as evidence of adaptive genome streamlining caused by strong purifying
      selection in large microbial populations. In such populations, even the small
      cost incurred by nonfunctional DNA because of extra energy and time expenditure
      is thought to be sufficient for this extra genetic material to be eliminated by
      selection. However, contrary to the predictions of this model, there exists a
      consistent, positive correlation between the strength of selection at the protein
      sequence level, measured as the ratio of nonsynonymous to synonymous substitution
      rates, and microbial genome size. Here, by fitting the genome size distributions
      in multiple groups of prokaryotes to predictions of mathematical models of
      population evolution, we show that only models in which acquisition of additional
      genes is, on average, slightly beneficial yield a good fit to genomic data. These
      results suggest that the number of genes in prokaryotic genomes reflects the
      equilibrium between the benefit of additional genes that diminishes as the genome
      grows and deletion bias (i.e., the rate of deletion of genetic material being
      slightly greater than the rate of acquisition). Thus, new genes acquired by
      microbial genomes, on average, appear to be adaptive. The tight spacing of
      protein-coding genes likely results from a combination of the deletion bias and
      purifying selection that efficiently eliminates nonfunctional, noncoding
      sequences.

PMID- 27702905
TI  - How seabirds plunge-dive without injuries.
AB  - In nature, several seabirds (e.g., gannets and boobies) dive into water at up to
      24 m/s as a hunting mechanism; furthermore, gannets and boobies have a slender
      neck, which is potentially the weakest part of the body under compression during
      high-speed impact. In this work, we investigate the stability of the bird's neck
      during plunge-diving by understanding the interaction between the fluid forces
      acting on the head and the flexibility of the neck. First, we use a salvaged bird
      to identify plunge-diving phases. Anatomical features of the skull and neck were
      acquired to quantify the effect of beak geometry and neck musculature on the
      stability during a plunge-dive. Second, physical experiments using an elastic
      beam as a model for the neck attached to a skull-like cone revealed the limits
      for the stability of the neck during the bird's dive as a function of impact
      velocity and geometric factors. We find that the neck length, neck muscles, and
      diving speed of the bird predominantly reduce the likelihood of injury during the
      plunge-dive. Finally, we use our results to discuss maximum diving speeds for
      humans to avoid injury.

PMID- 27702907
TI  - Reply to Adams et al.: Empirical versus process-based approaches to modeling
      temperature responses of leaf respiration.

PMID- 27702908
TI  - Different models provide equivalent predictive power for cross-biome response of
      leaf respiration to temperature.

PMID- 27702906
TI  - Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense
      suppression.
AB  - A premature termination codon (PTC) in the ORF of an mRNA generally leads to
      production of a truncated polypeptide, accelerated degradation of the mRNA, and
      depression of overall mRNA expression. Accordingly, nonsense mutations cause some
      of the most severe forms of inherited disorders. The small-molecule drug ataluren
      promotes therapeutic nonsense suppression and has been thought to mediate the
      insertion of near-cognate tRNAs at PTCs. However, direct evidence for this
      activity has been lacking. Here, we expressed multiple nonsense mutation
      reporters in human cells and yeast and identified the amino acids inserted when a
      PTC occupies the ribosomal A site in control, ataluren-treated, and
      aminoglycoside-treated cells. We find that ataluren's likely target is the
      ribosome and that it produces full-length protein by promoting insertion of near
      cognate tRNAs at the site of the nonsense codon without apparent effects on
      transcription, mRNA processing, mRNA stability, or protein stability. The
      resulting readthrough proteins retain function and contain amino acid
      replacements similar to those derived from endogenous readthrough, namely Gln,
      Lys, or Tyr at UAA or UAG PTCs and Trp, Arg, or Cys at UGA PTCs. These insertion
      biases arise primarily from mRNA:tRNA mispairing at codon positions 1 and 3 and
      reflect, in part, the preferred use of certain nonstandard base pairs, e.g., U-G.
      Ataluren's retention of similar specificity of near-cognate tRNA insertion as
      occurs endogenously has important implications for its general use in therapeutic
      nonsense suppression.

PMID- 27702899
TI  - Bayesian model reveals latent atrophy factors with dissociable cognitive
      trajectories in Alzheimer's disease.
AB  - We used a data-driven Bayesian model to automatically identify distinct latent
      factors of overlapping atrophy patterns from voxelwise structural MRIs of late
      onset Alzheimer's disease (AD) dementia patients. Our approach estimated the
      extent to which multiple distinct atrophy patterns were expressed within each
      participant rather than assuming that each participant expressed a single atrophy
      factor. The model revealed a temporal atrophy factor (medial temporal cortex,
      hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and
      cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal,
      and lateral occipital cortices). To explore the influence of each factor in early
      AD, atrophy factor compositions were inferred in beta-amyloid-positive (Abeta+)
      mild cognitively impaired (MCI) and cognitively normal (CN) participants. All
      three factors were associated with memory decline across the entire clinical
      spectrum, whereas the cortical factor was associated with executive function
      decline in Abeta+ MCI participants and AD dementia patients. Direct comparison
      between factors revealed that the temporal factor showed the strongest
      association with memory, whereas the cortical factor showed the strongest
      association with executive function. The subcortical factor was associated with
      the slowest decline for both memory and executive function compared with temporal
      and cortical factors. These results suggest that distinct patterns of atrophy
      influence decline across different cognitive domains. Quantification of this
      heterogeneity may enable the computation of individual-level predictions relevant
      for disease monitoring and customized therapies. Factor compositions of
      participants and code used in this article are publicly available for future
      research.

PMID- 27702910
TI  - Reversible Facial Hyperpigmentation Associated With Vitamin B12 Deficiency.
AB  - Vitamin B12 (cobalamin) deficiency is common in developing countries. Its
      dermatologic manifestations include hair and nail changes and glossitis. Cases of
      generalized hyperpigmentation associated with vitamin B12 deficiency have rarely
      been reported. Localized hyperpigmentation is less frequently described,
      affecting palms, soles, and flexural areas. We report a rare case of reversible
      melasma-like cutaneous hyperpigmentation associated with pernicious anemia and
      discuss the possible mechanisms of this association.

PMID- 27702909
TI  - Transcriptome analysis of trigeminal ganglia following masseter muscle
      inflammation in rats.
AB  - BACKGROUND: Chronic pain in masticatory muscles is a major medical problem.
      Although mechanisms underlying persistent pain in masticatory muscles are not
      fully understood, sensitization of nociceptive primary afferents following muscle
      inflammation or injury contributes to muscle hyperalgesia. It is well known that
      craniofacial muscle injury or inflammation induces regulation of multiple genes
      in trigeminal ganglia, which is associated with muscle hyperalgesia. However,
      overall transcriptional profiles within trigeminal ganglia following masseter
      inflammation have not yet been determined. In the present study, we performed RNA
      sequencing assay in rat trigeminal ganglia to identify transcriptome profiles of
      genes relevant to hyperalgesia following inflammation of the rat masseter muscle.
      RESULTS: Masseter inflammation differentially regulated >3500 genes in trigeminal
      ganglia. Predominant biological pathways were predicted to be related with
      activation of resident non-neuronal cells within trigeminal ganglia or
      recruitment of immune cells. To focus our analysis on the genes more relevant to
      nociceptors, we selected genes implicated in pain mechanisms, genes enriched in
      small- to medium-sized sensory neurons, and genes enriched in TRPV1-lineage
      nociceptors. Among the 2320 candidate genes, 622 genes showed differential
      expression following masseter inflammation. When the analysis was limited to
      these candidate genes, pathways related with G protein-coupled signaling and
      synaptic plasticity were predicted to be enriched. Inspection of individual gene
      expression changes confirmed the transcriptional changes of multiple nociceptor
      genes associated with masseter hyperalgesia (e.g., Trpv1, Trpa1, P2rx3, Tac1, and
      Bdnf) and also suggested a number of novel probable contributors (e.g., Piezo2,
      Tmem100, and Hdac9). CONCLUSION: These findings should further advance our
      understanding of peripheral mechanisms involved in persistent craniofacial muscle
      pain conditions and provide a rational basis for identifying novel genes or sets
      of genes that can be potentially targeted for treating such conditions.

PMID- 27702911
TI  - Sleep Apnea in Patients With Rett Syndrome: Roles for Polysomnography and
      Adenotonsillectomy.

PMID- 27702913
TI  - Psychosocial Factors Associated With Smoking Intention in Korean Male Middle
      School Students.
AB  - This study examined psychosocial factors influencing smoking intention in Korean
      male middle school students. We used a descriptive cross-sectional design, based
      on the biopsychosocial model, to analyze data from 309 male adolescents aged 14
      16 years in middle school. Of the psychological factors examined, stress and risk
      taking tendency were significantly associated with smoking intention. Of the
      social factors examined, social normative beliefs, close friends' and siblings'
      smoking, and low socioeconomic status were significant factors in smoking
      intention. The explanatory power of these variables in the predictive model was
      23.1%. In conclusion, the unique psychological and social characteristics of
      adolescents should be reflected in interventions for smoking prevention.

PMID- 27702912
TI  - Frontal Hypoactivation During a Working Memory Task in Children With 22q11
      Deletion Syndrome.
AB  - Impairments in executive function, such as working memory, are almost universal
      in children with chromosome 22q11.2 deletion syndrome. Delineating the neural
      underpinnings of these functions would enhance understanding of these
      impairments. In this study, children and adolescents with 22q11 deletion syndrome
      were compared with healthy control participants in a functional magnetic
      resonance imaging (MRI) study of working memory. When the 2-back condition was
      contrasted with the 1-back and 0-back conditions, the participants with 22q11
      deletion syndrome showed lower activation in several brain areas involved in
      working memory-notably dorsolateral prefrontal cortex, anterior cingulate, and
      precuneus. This hypoactivation may be due to reduced gray matter volumes or white
      matter connectivity in the frontal and parietal regions, differences that have
      previously been documented in children with 22q11 deletion syndrome.
      Understanding differences in brain function will provide a foundation for future
      interventions to address the wide range of neurodevelopmental deficits observed
      in 22q11 deletion syndrome.

PMID- 27702914
TI  - Tanshinone IIA protects against pulmonary arterial hypertension in broilers.
AB  - This investigation was conducted to study the effects of tanshinone IIA (TIIA) on
      pulmonary arterial hypertension (PAH) in broilers. Two-hundred newly hatched
      Arbor Acre commercial broilers were randomly divided into 3 groups. All groups,
      with the exception of the control group (tap water), were given NaCl water (0.3%)
      starting on the d 15, and broilers in the protected group were fed a diet
      supplemented with TIIA (2.5 g/kg) starting on the d 15. On d 28, 35, 42, and 49,
      the ratio of the right ventricular weight to the total ventricular weight (RV:
      TV) and the values of other biochemical indicators for each group chickens were
      determined. The concentrations of interleukin-6 (IL-6), interleukin-1beta (IL
      1beta), nuclear factor kappa (NF-kappaB), and P38 (a mitogen-activated protein
      kinase) were measured using enzyme-linked immune sorbent assays (ELISA). The
      results showed that the proportion of chickens in the diseased group with an
      RV:TV ratio in the range of 0.250 to 0.299 (10%) was significantly higher (25 to
      30%) compared to that of the other groups (P < 0.05), and the proportion in all
      chickens was 28%. In addition, the IL-6, IL-1beta, NF-kappaB, and P38 protein
      concentrations were higher in the diseased group, whereas there were no
      differences between the control group and the protected group. Moreover, the
      measurements of body weight, liver function, kidney function and electrolytes
      showed significant differences between the diseased group and the other groups.
      These findings suggest that tanshinone IIA may protect broilers from PAH, which
      is an important piece of information for the poultry industry.

PMID- 27702915
TI  - Determination of resistance and virulence genes in Enterococcus faecalis and E.
      faecium strains isolated from poultry and their genotypic characterization by
      ADSRRS-fingerprinting.
AB  - The aim of this study was to determine the antimicrobial resistance of E.
      faecalis and E. faecium strains isolated from poultry and to carry out genotypic
      characterization thereof with the ADSRRS-fingerprinting method (amplification of
      DNA fragments surrounding rare restriction sites) and analysis of the genetic
      relatedness between the isolates with different resistance and virulence
      determinants. Samples were collected from 70 4-week-old chickens and tested for
      Enterococcus. Minimum inhibitory concentrations of 11 antimicrobials were
      determined using the broth microdilution method. Detection of antibiotic
      resistance and virulence genes was performed using PCR, and molecular analysis
      was carried out using the ADSRRS-fingerprinting method. The highest percentage of
      strains was resistant to tetracycline (60.5%) and erythromycin (54.4%), and a
      large number exhibited high-level resistance to both kanamycin (42.1%) and
      streptomycin (34.2%). Among 8 genes encoding AME, the tested strains showed
      mainly the presence of [aph(3?)-IIIa], [ant(6)-Ia], [aac(6?)-Ie-aph(2??)-Ia], and
      [ant(9)-Ia] genes. Phenotypic resistance to erythromycin was encoded in 98.4%
      strains by the ermB gene. Genotypic resistance to tetracycline in E. faecium was
      associated with the presence of tetM and tetL (respectively, in 95.5 and 57.7% of
      the isolates); in contrast, E. faecalis strains were characterized mainly by the
      presence of tetO (83.3%). The virulence profile was homogenous for all E. faecium
      strains and included only efaAfm and ccf genes. All E. faecalis strains exhibited
      efaAfs, gelE, and genes encoding sex pheromones. The strains tested exhibited 34
      genotypic profiles. Comparative analysis of phenotypic and genotypic resistance
      and virulence profiles and confrontation thereof with the genotypes of the
      strains tested showed that strains assigned to a particular genotype have an
      identical phenotypic resistance profile and a panel of resistance and virulence
      genes. The results of this study confirm that poultry can be a reservoir of
      resistant E. faecium and E. faecalis strains with multiple combinations of
      resistance and virulence genes, whose specific panel determines not only
      phenotypic characteristics but also has a strong correlation with the genotypic
      profiles of the strains.

PMID- 27702916
TI  - Evaluation of the efficacy of chitosan nanoparticles loaded PhiKAZ14
      bacteriophage in the biological control of colibacillosis in chickens.
AB  - Disease inflicted by avian pathogenic Escherichia coli (APEC) causes economic
      losses and burden to the poultry industry worldwide. In this study, the efficacy
      of chitosan nanoparticles loaded PhiKAZ14 (C-PhiKAZ14 NPs) as an oral biological
      therapy for Colibacillosis was evaluated. C-PhiKAZ14 NPs containing 107 PFU/ml of
      PhiKAZ14 (Myoviridae; T4-like coliphage) bacteriophage were used to treat
      experimentally APEC-infected COBB 500 broiler chicks. C-PhiKAZ14 NPs and PhiKAZ14
      bacteriophage were administered orally in a single dose. The clinical symptoms,
      mortality, and pathology in the infected birds were recorded and compared with
      those of control birds that did not receive C-PhiKAZ14 NPs or naked PhiKAZ14
      bacteriophage. The results showed that C-PhiKAZ14 NP intervention decreased
      mortality from 58.33 to 16.7% with an increase in the protection rate from 42.00
      to 83.33%. The bacterial colonization of the intestines of infected birds was
      significantly higher in the untreated control than in the C-PhiKAZ14 NP-treated
      group (2.30*109 +/- 0.02 and 0.79*103 +/- 0.10 CFU/mL, respectively) (P <= 0.05).
      Similarly, a significant difference in the fecal shedding of Escherichia coli was
      observed on d 7 post challenge between the untreated control and the C-PhiKAZ14
      NP-treated group (2.35*109 +/- 0.05 and 1.58*103 +/- 0.06 CFU/mL, respectively)
      (P <= 0.05). Similar trends were observed from d 14 until d 21 when the
      experiment was terminated. Treatment with C-PhiKAZ14 NPs improved the body
      weights of the infected chicks. A difference in body weight on d 7 post challenge
      was observed between the untreated control and the C-PhiKAZ14 NP-treated group
      (140 +/- 20 g and 160 +/- 20 g, respectively). The increase was significant (P <=
      0.05) on d 21 between the 2 groups (240 +/- 30 g and 600 +/- 80 g, respectively).
      Consequently, the clinical signs and symptoms were ameliorated upon treatment
      with C-PhiKAZ14 NPs compared with infected untreated birds. In all, based on the
      results, it can be concluded that the encapsulation of bacteriophage could
      enhance bacteriophage therapy and is a valuable approach for controlling APEC
      infections in poultry.

PMID- 27702917
TI  - Colonization of internal organs by Salmonella serovars Heidelberg and Typhimurium
      in experimentally infected laying hens housed in enriched colony cages at
      different stocking densities.
AB  - Contaminated eggs produced by infected commercial laying flocks are often
      implicated as sources of human infections with Salmonella Enteritidis, but
      Salmonella serovars Heidelberg and Typhimurium have also been associated with egg
      transmitted illness. Contamination of the edible contents of eggs is a
      consequence of the colonization of reproductive tissues in systemically infected
      hens. In recent years, the animal welfare implications of diverse poultry housing
      and management systems have been vigorously debated, but the food safety
      significance of laying hen housing remains uncertain. The present study evaluated
      the effects of 2 different bird stocking densities on the invasion of internal
      organs by Salmonella serovars Heidelberg and Typhimurium in groups of
      experimentally infected laying hens housed in colony cages enriched with perching
      and nesting areas. Laying hens were distributed at 2 different stocking densities
      (648 and 973 cm2/bird) into colony cages and (along with a group housed in
      conventional cages at 648 cm2/bird) orally inoculated with doses of 107 cfu of 2
      strain cocktails of either Salmonella Heidelberg or Salmonella Typhimurium. At 5
      to 6 d post-inoculation, hens were euthanized and samples of internal organs
      (cecum, liver, spleen, ovary, and oviduct) were removed for bacteriologic
      culturing. The overall frequency of Salmonella isolation from ceca after
      inoculation with strains of serovar Heidelberg (83.3%) was significantly (P <
      0.001) greater than the corresponding value for strains of serovar Typhimurium
      (53.8%), whereas Salmonella was recovered significantly more often from both
      livers (85.2% vs. 53.7%; P < 0.0001) and spleens (78.7% vs. 56.5%; P = 0.0008)
      after inoculation with strains of serovar Typhimurium than strains of serovar
      Heidelberg. However, there were no significant differences (P > 0.05) between
      stocking densities or cage systems in the frequencies of isolation of either
      Salmonella serovar from any of the five sampled tissues. These results contrast
      with prior studies, which reported increased susceptibility to internal organ
      invasion by Salmonella Enteritidis among hens in conventional cages at higher
      stocking densities.

PMID- 27702918
TI  - Effects of low-protein diets on growth performance and carcass yields of growing
      French meat quails (France coturnix coturnix).
AB  - A dose-response experiment with 5 analyzed dietary crude protein (CP) levels
      (17.61, 19.73, 21.58, 23.24, and 25.32%) was conducted to investigate the effects
      of low-protein diets on growth performance and carcass yields of French meat
      quails from 15 to 42 d of age. All diets were formulated to contain a similar
      dietary energy level and amino acid profile. A total of 400 fifteen-day-old
      French quails were divided into 5 experimental treatments and each treatment
      contained 4 replicate pens of 20 birds (10?+10?). At 42 d of age, weight gain,
      feed intake, CP intake, feed/gain, and the yields of breast part with bone, leg
      part with bone, and liver of quails from each pen were measured. The results
      showed significant effects of the low-CP diets on CP intake, weight gain, feed
      intake, and feed/gain at different experiment periods except for the sixth wk of
      age (P < 0.05). In addition, as dietary CP decreased from 25.32 to 17.61%, feed
      intake and feed/gain were increased linearly (P < 0.05), whereas CP intake showed
      the opposite trend and decreased gradually. On the other hand, the carcass yields
      of quail were not influenced by reducing dietary CP at 42 day of age (P > 0.05).
      Based on broken-line regression, 23.0%, 22.5%, and 20.4% were the minimum dietary
      CP to keep weight gain similar to the quails fed with 25.32% CP diets during the
      third, fourth, and fifth wk of age, respectively. In summary, with crystalline
      amino acid supplementation based on a similar amino acid profile, it was possible
      to formulate the low-protein diets containing about 22.0% CP for growing meat
      quails without adverse effects on growth and carcass yields of meat quails.

PMID- 27702919
TI  - Effect of climatic elements on Campylobacter colonization in broiler flocks
      reared in southern Japan from 2008 to 2012.
AB  - To demonstrate the effect of climatic elements on Campylobacter colonization in
      broiler chickens reared in Japan, the correlation between Campylobacter isolated
      from chickens (191 of 236 flocks, 80.9%) between 2008 and 2012 and climatic
      elements was analyzed by logistic regression. We divided the rearing process into
      13 terms of 5 d each (total: 65 d). Terms were numbered backwards, wherein a 0
      term lag was considered as the sampling day plus 4 d before sampling; 1-term lag
      was the 5-d term before the 0-term lag, and so on, until the 12-term lag. We
      obtained climatic data tracing back from the 0-term to the 12-term lags. For
      evaluation in each season, we divided chickens reared during periods of rising
      temperature (spring, summer) and decreasing temperature (autumn, winter). Air
      temperature showed a positive correlation with Campylobacter colonization from
      the 0- to 12-term lags in chickens reared during the period of rising temperature
      (odds ratio [OR], 1.069 to 1.104), and from the 0- to 4- and 6-term lags (OR,
      1.079 to 1.105) in chickens reared during the period of decreasing temperature.
      The strong positive effect of air temperature on Campylobacter colonization,
      particularly during the period of rising temperature, may be associated with the
      effect on the Campylobacter environmental sources and/or vectors. A positive
      correlation was observed between Campylobacter colonization and humidity when
      chicken houses were empty and new chicks were introduced (from the 9- to 12-term
      lags) during the period of decreasing temperature (OR, 1.076 to 1.141). Thus,
      high humidity would be an important factor causing carry-over of Campylobacter
      infection during the period of decreasing temperature. We also found that solar
      radiation increased Campylobacter colonization during the period of decreasing
      temperature, from the 2- to 8-term lags, except for the 4- and 5-term lags, in
      Japan. The results of this study demonstrate the effects of air temperature,
      humidity, and solar radiation on Campylobacter colonization in broiler chickens,
      and are potentially important for developing strategies to reduce the risk of
      Campylobacter contamination in broiler chickens.

PMID- 27702920
TI  - Effects of betaine on biological functions in meat-type ducks exposed to heat
      stress.
AB  - Heat stress in hot seasons is a major problem in poultry production, particularly
      in humid areas. The aim of this study was to determine the pharmacodynamics of
      betaine on the blood and cecal short chain fatty acid profile in meat-type ducks
      exposed to heat stress. Three-hundred-sixty meat-type ducks (Anas platyrhynchos
      domesticus) were randomly allocated into 4 treatments: C (heat stress control
      without betaine), T1 (700 ppm betaine), T2 (1,000 ppm betaine), and T3 (1,300 ppm
      betaine). Each treatment had 6 replicated pens with 15 meat-type ducks per pen.
      The study was conducted for 42 days. Our findings revealed that the betaine group
      had higher body weight gain compared to the control group under heat stress (P <
      0.05). Betaine supplementation resulted in more significant improvement in
      hematological indicators such as RBCs and platelet counts than the heat stress
      control group (P < 0.05). Under the heat-wave environment, supplementation of
      betaine manifested a significant decrease in blood pH (P < 0.05) but not in
      electrolytes (Na+, K+ and Cl-) and gas concentration. The concentration of short
      chain fatty acids (SCFA) in the cecum was higher than the control under heat
      stress conditions. The total SCFA, acetic acid, and propionic acid production was
      higher in the betaine supplemented groups compared to the heat stress control
      group (P < 0.05). Results showed that betaine supplementation has beneficial
      effects in meat-type ducks under heat stress on short chain fatty acid levels,
      blood biochemical parameters, and body weight.

PMID- 27702921
TI  - Estimation of the maximum safe level of feed ingredients by spline or broken-line
      nonlinear regression models.
AB  - The use of non-linear regression models in the analysis of biological data has
      led to advances in poultry nutrition. Spline or broken-line nonlinear regression
      models are commonly used to estimate nutritional requirements. One particular
      application of broken-line models is estimating the maximum safe level (MSL) of
      feed ingredients beyond which the ingredients become toxic, resulting in reduced
      performance. The objectives of this study were to evaluate the effectiveness of
      broken-line models (broken-line linear or BLL; and broken-line quadratic or BLQ)
      in estimating the MSL; to identify the most efficient design of feeding trials by
      finding the optimal number of ingredient levels and replications; and to re
      estimate the MSL of various test ingredients reported in the nutrition literature
      for comparison purposes. The Maximum Ingredient level Optimization Workbook
      (MIOW) was developed to simulate a series of experiments and estimate the MSL and
      the corresponding descriptive statistics (SD, SE, CI, and R2). The results showed
      that the broken-line models provided good estimates of the MSL (small SE and high
      R2) with the BLL model producing higher MSL values as compared to the BLQ model.
      Increasing the number of experimental replications or ingredient levels
      (independently of each other) reduced the SE of the MSL with diminishing returns.
      The SE of the MSL was reduced with increasing the size (total pens) of the
      simulated experiments by increasing either the number of replications or levels
      or both. The evaluation of MSLs reported in the existing literature revealed that
      the multiple range procedure used to determine the MSL in several reports can
      both overestimate and underestimate the MSL compared to the results obtained by
      the broken-line models. The results suggest that the broken-line linear models
      can be used in lieu of the multiple range test to estimate the MSL of feed
      ingredients along with the corresponding descriptive statistics, such as the SE
      of the MSL.

PMID- 27702922
TI  - Broiler chickens dead on arrival: associated risk factors and welfare indicators.
AB  - The pre-slaughter phase of the production process has potentially important
      animal welfare implications, including mortality (recorded as "Dead on Arrivals";
      DOA: ). To reduce DOA%, specific risk factors need to be identified. DOA% can
      also be used as a first and quick screening of pre-slaughter broiler welfare
      under commercial conditions. The aim of the present study was to identify risk
      factors for DOA% in commercial broiler flocks and to find associations between
      DOA% and animal-based indicators of broiler welfare during the pre-slaughter
      phase. Eighty-one transported flocks to five slaughter plants were assessed.
      Farmers provided information on the flock and observers gathered data on pre
      slaughter factors. DOA% was recorded by slaughter plant personnel. The
      association between risk factors and DOA% was tested using linear mixed models,
      with slaughter plant as the random effect. Mean (+/- SE) DOA% was 0.30 +/- 0.05%
      and median was 0.19% (range 0.04 to 3.34%). Two risk factors for DOA% were
      identified, both related to flock health status during the production phase.
      Higher DOA% was found when farmers did not check chick quality upon arrival (P =
      0.011), although one extreme DOA% caused this significant effect. In addition, on
      farm mortality during production (including selective culling) was negatively
      associated with DOA% (P = 0.011), potentially due to the selective culling on
      farm. Further research is needed on the impact of on-farm health status on
      welfare during the pre-slaughter phase, as the current study provided some
      evidence that on-farm factors are linked to mortality during the pre-slaughter
      phase. No specific characteristics of the pre-slaughter phase could be identified
      as risk factor for increased mortality. DOA% was positively associated with five
      welfare indicators, including indicators of thermal stress, which indicates the
      potential to use DOA% as a quick, cost-efficient screening tool for those welfare
      aspects.

PMID- 27702923
TI  - Impact of the separate pre-slaughter stages on broiler chicken welfare.
AB  - Before broilers are slaughtered, several parties are involved in catching,
      loading, transportation and lairage. During these pre-slaughter activities,
      broilers are exposed to a variety of stressors. A detailed understanding of how
      broiler welfare is impaired during each stage could help the responsible parties
      to make targeted improvements. The aim of this study was to identify welfare
      problems occurring during the consecutive stages of commercial broiler
      transportation and to identify risk factors associated with the identified
      welfare problems. Commercial Belgian transports (n = 81) were assessed in spring
      (n = 14), summer (n = 33), autumn (n = 10), and winter (n = 24), and potential
      risk factors were recorded by the observer. Animal-based welfare indicators were
      scored before the start of the pre-slaughter phase as well as after the catching,
      transport and lairage, and slaughter stages to assess the impact of each stage.
      The most frequently observed welfare impairments were vent and thigh lesions,
      panting, wing fractures, and bruising on wings and breasts. Our results show that
      the impact of the pre-slaughter phase on broiler welfare is multifaceted. The
      overall pre-slaughter phase resulted in a mean weight decrease of 5.3%, a
      prevalence of 1.4% in leg bruising, and 3.7% in breast or wing bruising. Wing
      fractures occurred mainly during the catching stage: Prevalence increased from
      0.1% to 1.9% (P = 0.003). A welfare comparison before and after transportation
      and lairage revealed that plumage had become more soiled (P = 0.003), body
      temperature decreased by 0.7 degrees C (P < 0.001), huddling prevalence increased
      by 0.5% (P = 0.008), prevalence of birds with splayed legs increased by 0.08% (P
      = 0.008), prevalence of supine birds decreased by 0.05% (P = 0.003), and 0.1%
      fewer birds with wings stuck in the crates (P = 0.010) were observed. Risk factor
      analyses revealed that carefully choosing the catching crew, minimizing thermal
      stress, reducing duration of transportation, and worker training are promising
      actions that may improve broiler welfare during the pre-slaughter phase.

PMID- 27702924
TI  - Effect of acute heat stress and slaughter processing on poultry meat quality and
      postmortem carbohydrate metabolism.
AB  - This study investigated the effects of acute heat stress and slaughter processing
      on poultry meat quality and carbohydrate metabolism. Broilers (200) were randomly
      divided into 2 groups receiving heat stress (HS; 36 degrees C for one h),
      compared to a non-stressed control (C). At slaughter, each group was further
      divided into 2 groups for slaughter processing (L = laboratory; F = commercial
      factory). L group breasts were removed immediately after bleeding without carcass
      scalding or defeathering, and stored at 4 degrees C. F group broilers were
      scalded (60 degrees C, 45 s) after bleeding and defeathering. Then the breasts
      were removed and cooled in ice water until the core temperature was <=4 degrees
      C. Rates of Pectoralis core temperature and pH decline were changed by slaughter
      processing, but only HS affected ultimate pH in group L. HS muscles had higher L*
      values (P < 0.05) than controls at 24 h postmortem. Laboratory processing "hot
      deboning" increased drip loss, which resulted in a lower cooked loss (P < 0.05).
      Postmortem glycolysis was affected only by HS. The speed of lactic acid
      accumulation and glycogen degradation was faster in the HS group than controls at
      5 min postmortem. During storage the glycolysis rates were not different (P >
      0.05). Sarcoplasmic protein solubility was higher in F processed birds (P <
      0.05). HS decreased the solubility of myofibrillar and total protein in the L
      slaughtered birds. Thus, HS caused a higher frequency of accelerated muscle
      glycolysis than controls. Factory processing (chilling) could not completely
      eliminate the effects of accelerated glycolysis caused by pre-slaughter HS.

PMID- 27702925
TI  - Distribution of Campylobacter jejuni multilocus sequence types isolated from
      chickens in Poland.
AB  - Poultry is recognized as the most important source of food-related transmission
      of Campylobacter jejuni to humans and campylobacteriosis is the most commonly
      reported zoonotic bacterial disease in the European Union. It has been documented
      that C. jejuni is genetically diverse and analyses of bacterial isolates usually
      show a large strain variety. Therefore, molecular typing of strains represents an
      important tool to study the genetic diversity of isolates and to trace individual
      strains that cause human infections. The aim of the study was characterization of
      genetic population structure and antimicrobial resistance (AMR) of C. jejuni
      isolated from Polish chickens. C. jejuni from chicken ceca and the corresponding
      carcasses (72 and 61 strains, respectively), originating from 128 flocks in
      Poland during February 2011 and May 2013, were used in the study. The isolates
      were tested for their population structure and genetic diversity using a
      multilocus sequence typing (MLST) scheme with connection to their antimicrobial
      resistance. The molecular analysis of 133 C. jejuni generated 39 different
      sequence types (ST); 3 of them were defined for the first time. Additionally, 16
      STs were represented by single isolates. The most common STs observed were 6411
      (16.5% isolates) and 257 (15.0% strains). The first mentioned ST was resistant to
      3 different classes of antibiotics, i.e., quinolones, tetracyclines, and
      aminoglycosides. Overall, 125 (94.4%) of C. jejuni isolates demonstrated
      antimicrobial resistance and the most frequent AMR profile observed was
      ciprofloxacin, nalidixic acid, tetracycline (47.4% strains). Likewise, the clonal
      complexes CC 257 and CC 353 were defined as the predominant molecular groups
      covering altogether 37 C. jejuni strains. No associations between CCs and the
      origin of the samples as well as the place of isolation were found. This study
      highlights that the C. jejuni population from chickens in Poland was diverse and
      showed a weak clonal structure.

PMID- 27702926
TI  - Retreatment of a choroidal vein of Galen malformation with embolization 42 years
      after open surgical treatment in the neonatal period.
AB  - In 1976 an infant boy initially presented with a choroidal vein of Galen
      malformation (cVOGM). Craniotomy and clipping of the anterior cerebral artery and
      posterior choroidal arteries was performed, which was reported in the literature
      40 years ago. The patient remained asymptomatic until age 42 when he re-presented
      with an isolated intraventricular hemorrhage. Angiography demonstrated cVOGM with
      venous sinus occlusive disease leading to venous hypertension and subsequent
      intraventricular hemorrhage. The angiogram also demonstrated a 'pseudo-nidus'
      composed of multiple arterial-to-arterial anastomoses that had developed as a
      result of the original surgical treatment. We embolized a portion of the lesion
      to reduce the venous hypertension. The patient has been asymptomatic for more
      than 2 years. To our knowledge, this is the first reported case of a symptomatic
      neonatal VOGM treated with open surgery that required embolization as an adult
      for a delayed hemorrhagic presentation.

PMID- 27702927
TI  - Spinal tophaceous gout encasing the thoracic spinal cord.
AB  - Gout rarely compresses the thoracic spinal cord. A 43-year-old man presented with
      lower limb paraparesis. MRI showed a soft tissue swelling at the level of
      T10/T11. He was managed with a laminectomy and evacuation of a presumed abscess
      and started on intravenous antibiotics. However, histology confirmed tophaceous
      gout.

PMID- 27702928
TI  - Acute onset blindness: a case of optic neuritis and review of childhood optic
      neuritis.
AB  - Optic neuritis (ON) is an acquired disorder of the optic nerve due to
      inflammation, demyelination or degeneration. We report a child who presented with
      acute onset bilateral visual loss who, following a diagnosis of ON, was treated
      and had excellent visual recovery. Paediatric ON is considered to be different
      clinical entity to adult ON. Although in children ON is usually parainfectious or
      postinfectious, it can be the first presenting feature of multiple sclerosis or
      neuromyelitis optica spectrum disease. In this paper, we discuss the literature
      on treatment of ON and prediction of risk of recurrence.

PMID- 27702929
TI  - Aortic valve replacement for Libman-Sacks endocarditis.
AB  - A 24-year-old man with systemic lupus erythematosus and antiphospholipid syndrome
      complicated by lupus nephritis presented with acute limb ischaemia secondary to
      an embolus. Following embolectomy, the patient underwent a transthoracic
      echocardiogram which revealed a large vegetation on all three cusps of the aortic
      valve. The patient was taken for an urgent aortic valve replacement with a
      mechanical valve. Cultures of one cusp remained sterile. Histopathological
      examination of the remaining two cusps revealed sterile fibrin-rich thrombotic
      vegetations characteristic of non-bacterial thrombotic endocarditis.

PMID- 27702930
TI  - Triple threat in pregnancy.
AB  - A woman aged 22 years with a history of lupus presented in the 18th week of
      pregnancy with hypertensive emergency and flash pulmonary oedema. Bedside
      echocardiogram revealed severe left ventricular (LV) dysfunction with an ejection
      fraction (EF) of 25% and pericardial effusion. Laboratories revealed
      hypocomplementemia, proteinuria, elevated C reactive protein and anti-DS-DNA,
      raising concern for a lupus flare. Cardiac MRI showed an acute intramyocardial
      oedematous process, consistent with lupus carditis, and further worsening of LVEF
      to 13%. Shared-decision-making with the patient included discussion of maternal
      risks of continuation of pregnancy in the setting of worsening heart function and
      the fetal risks of definitive treatment with cyclophosphamide for a lupus flare
      and the patient decided to proceed with medical termination of pregnancy.
      Treatment with immunosuppressants, including cyclophosphamide, and steroids, was
      then initiated. 2 months after discharge, cardiac MRI showed marked improvement
      in LVEF to 50% and the patient remains clinically free of heart failure.

PMID- 27702932
TI  - 'Dot in circle sign': a characteristic finding in ultrasound and MR imaging of
      soft tissue mycetomas.

PMID- 27702931
TI  - Massive iatrogenic orbital cysts following glaucoma drainage implant and
      strabismus surgery.
AB  - We describe 2 paediatric patients who developed large orbital conjunctival
      epithelium-lined inclusion cysts postsurgery. Case 1 underwent Ahmed glaucoma
      valve implant surgery 8 months ago and case 2 underwent strabismus surgery 7
      years ago. Both cases had either symptomatic strabismus or a mass causing some
      degree of proptosis or incomitance due to lesions in the intraorbital space.
      Following total excision of the cysts all associated symptoms were resolved.
      Conjunctival cysts following ocular surgery can develop anywhere in the anterior
      segment; however, large orbital cysts following anterior segment surgery are
      quite rare. We think that implantation cysts should be considered in the
      differential diagnosis of patients that have signs of orbital mass with a history
      of previous anterior segment surgery. Complete excision of the cysts results in
      resolution of all associated signs and symptoms.

PMID- 27702933
TI  - Erdheim-Chester disease: 25-year history with early CNS involvement.
AB  - We report a case of Erdheim-Chester disease (ECD) with a 25-year history
      following initial presentation with diabetes insipidus and brainstem involvement.
      The exceptionally long history is particularly notable, given that ECD is a life
      threatening disorder and there is a recognised association between central
      nervous system involvement and poor outcome. The case is a timely reminder of the
      presenting features of the condition, given the emergence of potential new
      treatment options.

PMID- 27702934
TI  - Efficacy of extracorporeal ultrafiltration in patients with diuretic-resistant
      heart failure.
AB  - Renal congestion contributes to the cardiorenal syndrome. There are some heart
      failure cases that are refractory to diuretic therapy. If the dose of diuretics
      is titrated, it leads to irreversible renal dysfunction. Early administration of
      tolvaptan is effective in treating fluid retention and congestion. However, in
      case of tolvaptan resistance, starting extracorporeal ultrafiltration (ECUM) at
      an early stage should be considered. Tolvaptan has been proven efficient, and we
      believe it should be incorporated with the classical method, ECUM. Herein, we
      present a case of successful application of ECUM to a heart failure patient
      refractory to any diuretics and tolvaptan.

PMID- 27702935
TI  - Rare presentation of a localised malignant pleural mesothelioma with cranial
      metastasis.
AB  - Mesothelioma is an uncommon malignant neoplasm and a localised form of the pleura
      is especially very rare. Diagnosis of localised malignant pleural mesothelioma
      (LMPM) is very challenging. Histopathological verification is the gold standard,
      and studies such as CT, positron emission tomography (PET) and thoracoscopy are
      very valuable tools in assisting diagnosis. We report a case of
      histopathologically proven LMPM, which was discovered as a well circumscribed
      solitary subpleural nodule on PET-CT after presentation with cranial metastasis.
      This case shows that LMPM can present with uncommon radiological and clinical
      appearances, and imaging tools such as PET-CT have a very important role in
      diagnosis.

PMID- 27702936
TI  - Functional and symptomatic assessment of medico-legal claims after upper limb
      injuries.
AB  - A consecutive group of 250 patients underwent medico-legal assessment at a mean
      of 24 (+/-13) months following upper limb injuries. Each had completed
      questionnaires to assess function (Quick-DASH) and cold intolerance (CIQ36)
      before clinical assessment following which their whole limb impairment percentage
      was calculated. The mean(+/-SD) whole limb impairment, QDASH and CIQ36 scores
      were 9(+/-14)%, 43(+/-24) and 17(+/-10), respectively. There was a significant
      correlation between whole limb impairment and QDASH, although some patients
      reported surprisingly high disability levels despite minimal or no objective
      functional impairment. Whilst useful qualitative information can be obtained from
      questionnaires, the correlation between subjective and objective scores is weak
      albeit statistically significant. Individual patients can show marked
      discrepancies between objective and subjective functional scores. The results of
      questionnaires in individual medico-legal patients should be treated with
      caution.

PMID- 27702938
TI  - Illicit Fentanyl-Related Fatalities in Florida: Toxicological Findings.
AB  - Fentanyl induces pharmacological effects and abuse liability comparable to other
      prescription opioids and heroin. A surge in fentanyl-related fatalities has been
      periodically reported throughout the USA. The University of Florida Forensic
      Toxicology Laboratory observed a significant increase in fentanyl-related deaths
      starting in mid-2014. The present report evaluated toxicological findings,
      demographics of the decedents and circumstances of death in the postmortem cases
      that were submitted to the laboratory for toxicological analysis from July 2014
      to January 2015 and that were tested for fentanyl in biological specimens. The
      cases originated from 6 of the 24 Florida Medical Examiner Districts, with the
      majority from District 12 (Desoto, Manatee and Sarasota counties). The specimens
      were analyzed for fentanyl by gas chromatography-mass spectrometry; the limit of
      detection (LOD) was 0.62 ng/mL and the limit of quantification (LOQ) was 2.5
      ng/mL. During the 7-month period, the laboratory tested 143 postmortem cases for
      fentanyl and 50% had quantifiable fentanyl in postmortem blood. Fentanyl
      concentrations ranged from 2.5 to 68 ng/mL (n = 66; median: 9.8 ng/mL); six cases
      were positive for fentanyl >LOD but <LOQ. The majority of the cases (85%) had
      indications of possible drug abuse with heroin use being the most often
      suspected. Concurrent detection of 6-acetylmorphine, morphine and cocaine along
      with other opioids and benzodiazepines was common. Of the 59 deaths from District
      12, the cause of death was accidental drug intoxication with fentanyl as a sole
      or contributing factor for 57 cases (two non-drug intoxication deaths). The
      median age of the 57 decedents was 35 (range: 19-63) years. Males represented 87%
      of the deaths and 96% were Whites. Most of the decedents (n = 53) had no
      prescription for fentanyl. Considering fentanyl's high potency and abuse
      liability, the recent rise in fentanyl-related deaths is a serious public health
      concern and signifies the urgent need to establish prevention and treatment
      efforts.

PMID- 27702939
TI  - Degradation of Opioids and Opiates During Acid Hydrolysis Leads to Reduced
      Recovery Compared to Enzymatic Hydrolysis.
AB  - Drug monitoring laboratories utilize a hydrolysis process to liberate the opiates
      from their glucuronide conjugates to facilitate their detection by tandem mass
      spectrometry (MS). Both acid and enzyme hydrolysis have been reported as viable
      methods, with the former as a more effective process for recovering codeine-6
      glucuronide and morphine-6-glucuronide. Here, we report concerns with acid
      catalyzed hydrolysis of opioids, including a significant loss of analytes and
      conversions of oxycodone to oxymorphone, hydrocodone to hydromorphone and codeine
      to morphine. The acid-catalyzed reaction was monitored in neat water and patient
      urine samples by liquid chromatography-time-of-flight and tandem MS. These side
      reactions with acid hydrolysis may limit accurate quantitation due to loss of
      analytes, possibly lead to false positives, and poorly correlate with
      pharmacogenetic profiles, as cytochrome P450 enzyme (CYP2D6) is often involved
      with oxycodone to oxymorphone, hydrocodone to hydromorphone and codeine to
      morphine conversions. Enzymatic hydrolysis process using the purified,
      genetically engineered beta-glucuronidase (IMCSzyme(r)) addresses many of these
      concerns and demonstrates accurate quantitation and high recoveries for
      oxycodone, hydrocodone, oxymorphone and hydromorphone.

PMID- 27702941
TI  - Genome-wide association study of caffeine metabolites provides new insights to
      caffeine metabolism and dietary caffeine-consumption behavior.
AB  - Caffeine is the most widely consumed psychoactive substance in the world and
      presents with wide interindividual variation in metabolism. This variation may
      modify potential adverse or beneficial effects of caffeine on health. We
      conducted a genome-wide association study (GWAS) of plasma caffeine,
      paraxanthine, theophylline, theobromine and paraxanthine/caffeine ratio among up
      to 9,876 individuals of European ancestry from six population-based studies. A
      single SNP at 6p23 (near CD83) and several SNPs at 7p21 (near AHR), 15q24 (near
      CYP1A2) and 19q13.2 (near CYP2A6) met GW-significance (P < 5 * 10-8) and were
      associated with one or more metabolites. Variants at 7p21 and 15q24 associated
      with higher plasma caffeine and lower plasma paraxanthine/caffeine (slow caffeine
      metabolism) were previously associated with lower coffee and caffeine consumption
      behavior in GWAS. Variants at 19q13.2 associated with higher plasma
      paraxanthine/caffeine (slow paraxanthine metabolism) were also associated with
      lower coffee consumption in the UK Biobank (n = 94 343, P < 1.0 * 10-6). Variants
      at 2p24 (in GCKR), 4q22 (in ABCG2) and 7q11.23 (near POR) that were previously
      associated with coffee consumption in GWAS were nominally associated with plasma
      caffeine or its metabolites. Taken together, we have identified genetic factors
      contributing to variation in caffeine metabolism and confirm an important
      modulating role of systemic caffeine levels in dietary caffeine consumption
      behavior. Moreover, candidate genes identified encode proteins with important
      clinical functions that extend beyond caffeine metabolism.

PMID- 27702943
TI  - Insurance, The ACA, Care In India, And More.

PMID- 27702944
TI  - Health Care Reform And A Failed Vision Of Bipartisanship.
AB  - The Affordable Care Act transformed health care in the United States. What hasn't
      changed is the partisan landscape in which it became law.

PMID- 27702942
TI  - Trans-ethnic meta-analysis of genome-wide association studies for Hirschsprung
      disease.
AB  - Hirschsprung disease (HSCR) is the most common cause of neonatal intestinal
      obstruction. It is characterized by the absence of ganglia in the nerve plexuses
      of the lower gastrointestinal tract. So far, three common disease-susceptibility
      variants at the RET, SEMA3 and NRG1 loci have been detected through genome-wide
      association studies (GWAS) in Europeans and Asians to understand its genetic
      etiologies. Here we present a trans-ethnic meta-analysis of 507 HSCR cases and
      1191 controls, combining all published GWAS results on HSCR to fine-map these
      loci and narrow down the putatively causal variants to 99% credible sets. We also
      demonstrate that the effects of RET and NRG1 are universal across European and
      Asian ancestries. In contrast, we detected a European-specific association of a
      low-frequency variant, rs80227144, in SEMA3 [odds ratio (OR) = 5.2, P = 4.7 * 10
      10]. Conditional analyses on the lead SNPs revealed a secondary association
      signal, corresponding to an Asian-specific, low-frequency missense variant
      encoding RET p.Asp489Asn (rs9282834, conditional OR = 20.3, conditional P = 4.1 *
      10-14). When in trans with the RET intron 1 enhancer risk allele, rs9282834
      increases the risk of HSCR from 1.1 to 26.7. Overall, our study provides further
      insights into the genetic architecture of HSCR and has profound implications for
      future study designs.

PMID- 27702945
TI  - Quality Of Health Care In India: Challenges, Priorities, And The Road Ahead.
AB  - India's health care sector provides a wide range of quality of care, from
      globally acclaimed hospitals to facilities that deliver care of unacceptably low
      quality. Efforts to improve the quality of care are particularly challenged by
      the lack of reliable data on quality and by technical difficulties in measuring
      quality. Ongoing efforts in the public and private sectors aim to improve the
      quality of data, develop better measures and understanding of the quality of
      care, and develop innovative solutions to long-standing challenges. We summarize
      priorities and the challenges faced by efforts to improve the quality of care. We
      also highlight lessons learned from recent efforts to measure and improve that
      quality, based on the articles on quality of care in India that are published in
      this issue of Health Affairs The rapidly changing profile of diseases in India
      and rising chronic disease burden make it urgent for state and central
      governments to collaborate with researchers and agencies that implement programs
      to improve health care to further the quality agenda.

PMID- 27702946
TI  - Trends In State-Level Child Mortality, Maternal Mortality, And Fertility Rates In
      India.
AB  - Trends in child mortality, maternal mortality, and fertility in India reveal wide
      variation across states. As a whole, India performs worse than many other low-
      and middle-income countries, although its rates of improvement have recently
      increased. Differences in health systems and adopted policies may account for
      some of the variation across Indian states.

PMID- 27702947
TI  - Socioeconomic Status And Quality Of Care In Rural India: New Evidence From
      Provider And Household Surveys.
AB  - To assess socioeconomic differences in access to high-quality health care
      services, we collected novel data on illnesses that required primary care from
      23,275 households in 100 villages in Madhya Pradesh, India. We matched the
      primary care visits for those illnesses to characteristics of the health care
      providers that members of the households visited. People in the average village
      in our sample could access eleven providers, of whom 71 percent were in the
      private sector and 49 percent had no formal medical training. The private sector
      accounted for 89 percent of the primary care visits in our sample, with 77
      percent of the visits made to providers with no formal training. Both access to
      and use of more knowledgeable providers increased with socioeconomic status,
      mostly as a result of differences across districts and villages. Strikingly,
      people in high- and low-socioeconomic-status households in the same village
      visited equally knowledgeable providers. It was the poor people who lived in poor
      communities who received especially low-quality care.

PMID- 27702948
TI  - Ambulance Service Associated With Reduced Probabilities Of Neonatal And Infant
      Mortality In Two Indian States.
AB  - India had no large-scale, centralized emergency medical system or ambulance
      service until 2005. Since then, the GVK Emergency Management and Research
      Institute (GVK EMRI) has emerged as India's largest ambulance service provider,
      covering more than 630 million people. This study provides the first quantitative
      evidence of GVK EMRI's early impact on population-level infant and maternal
      health outcomes in Andhra Pradesh and Gujarat, two Indian states with a combined
      population of about 145 million people. We found that GVK EMRI coverage is
      associated with reductions in the probability of neonatal and infant mortality as
      well as delivery complications (statewide in Andhra Pradesh and in high-mortality
      districts in Gujarat). However, we found little change in the probability of
      institutional delivery or skilled birth attendance. Taken together, our findings
      suggest that population-level health gains were achieved through improvements in
      the quality (rather than quantity) of maternal and neonatal health services-an
      interpretation consistent with qualitative reports. More research on this topic
      is needed.

PMID- 27702949
TI  - A Sustainable Model For Delivering High-Quality, Efficient Cataract Surgery In
      Southern India.
AB  - Cataracts are a leading cause of reversible blindness in India, where millions of
      people can be effectively treated for this condition with surgery. The Aravind
      Eye Care System in southern India developed an efficient system for delivering
      high-quality and low-cost cataract surgery. We provide a detailed accounting of
      costs of cataract surgery at the system and a cost-utility analysis. Total costs
      per operation were US$120, or $195 per quality-adjusted life-year gained. Using
      these data and population-based estimates of cataract prevalence, we calculate
      that eliminating cataract-related blindness and low vision in India would cost
      $2.6 billion and would yield a net societal benefit of $13.5 billion. Factors
      contributing to the highly cost-effective care at the Aravind Eye Care System
      include the domestic manufacturing of supplies, the use of a specialized
      workforce and standardized protocols, and the presence of few regulatory hurdles.
      Lessons learned from the system can help improve the delivery of cataract surgery
      and other ambulatory care surgeries in India and abroad.

PMID- 27702950
TI  - Lessons From Low-Cost, High-Quality Eye Care.
AB  - In the successful treatment of cataracts in India, researchers find valuable
      lessons for countries around the world.

PMID- 27702951
TI  - India's Largest Hospital Insurance Program Faces Challenges In Using Claims Data
      To Measure Quality.
AB  - The routine data generated by India's universal coverage programs offer an
      important opportunity to evaluate and track the quality of health care
      systematically and on a large scale. We examined the potential and challenges of
      measuring the quality of hospital care through claims data from India's hospital
      insurance program for the poor, Rashtriya Swasthya Bima Yojana (RSBY). Using data
      from one district in India, we illustrate how these data already provide useful
      insights and show that simple efforts to enhance data quality and an effort to
      expand the data captured could facilitate RSBY's ability to track quality of
      care. The data collected by RSBY has significant potential to characterize and
      uncover the provision of low-quality care and help inform much-needed efforts to
      raise the quality of hospital care.

PMID- 27702952
TI  - Effect Of A Large-Scale Social Franchising And Telemedicine Program On Childhood
      Diarrhea And Pneumonia Outcomes In India.
AB  - Despite the rapid growth of social franchising, there is little evidence on its
      population impact in the health sector. Similar in many ways to private-sector
      commercial franchising, social franchising can be found in sectors with a social
      objective, such as health care. This article evaluates the World Health Partners
      (WHP) Sky program, a large-scale social franchising and telemedicine program in
      Bihar, India. We studied appropriate treatment for childhood diarrhea and
      pneumonia and associated health care outcomes. We used multivariate difference-in
      differences models to analyze data on 67,950 children ages five and under in 2011
      and 2014. We found that the WHP-Sky program did not improve rates of appropriate
      treatment or disease prevalence. Both provider participation and service use
      among target populations were low. Our results do not imply that social
      franchising cannot succeed; instead, they underscore the importance of
      understanding factors that explain variation in the performance of social
      franchises. Our findings also highlight, for donors and governments in
      particular, the importance of conducting rigorous impact evaluations of new and
      potentially innovative health care delivery programs before investing in scaling
      them up.

PMID- 27702953
TI  - Marketplaces Helped Drive Coverage Gains In 2015; Affordability Problems
      Remained.
AB  - Health insurance coverage through the Marketplaces increased in 2015, with more
      nonelderly adult enrollees insured all year and fewer reporting health care
      affordability problems than in 2014. In 2015 more Marketplace enrollees in
      Medicaid nonexpansion states reported trouble paying family medical bills,
      compared to those in expansion states (23 percent versus 15 percent).

PMID- 27702954
TI  - Insurance Churning Rates For Low-Income Adults Under Health Reform: Lower Than
      Expected But Still Harmful For Many.
AB  - Changes in insurance coverage over time, or "churning," may have adverse
      consequences, but there has been little evidence on churning since implementation
      of the major coverage expansions in the Affordable Care Act (ACA) in 2014. We
      explored the frequency and implications of churning through surveying 3,011 low
      income adults in Kentucky, which used a traditional expansion of Medicaid;
      Arkansas, which chose a "private option" expansion that enrolled beneficiaries in
      private Marketplace plans; and Texas, which opted not to expand. We also compared
      2015 churning rates in these states to survey data from 2013, before the coverage
      expansions. Nearly 25 percent of respondents in 2015 changed coverage during the
      previous twelve months-a rate lower than some previous predictions. We did not
      find significantly different churning rates in the three states over time. Common
      causes of churning were job-related changes and loss of eligibility for Medicaid
      or Marketplace subsidies. Churning was associated with disruptions in physician
      care and medication adherence, increased emergency department use, and worsening
      self-reported quality of care and health status. Even churning without gaps in
      coverage had negative effects. Churning remains a challenge for many Americans,
      and policies are needed to reduce its frequency and mitigate its negative
      impacts.

PMID- 27702955
TI  - Gaining Coverage In 2014: New Estimates Of Marketplace And Medicaid Transitions.
AB  - We used data from the Medical Expenditure Panel Survey-Household Component to
      examine coverage transitions for nonelderly US adults. We found that 71.5 percent
      of Marketplace enrollees in 2014 had some period of uninsurance before
      enrollment. In Medicaid expansion states, 17.4 percent of adults who were
      uninsured throughout 2013 gained Medicaid coverage in 2014, compared with only
      5.6 percent in those states between 2012 and 2013.

PMID- 27702956
TI  - Access To Care Improved For People Who Gained Medicaid Or Marketplace Coverage In
      2014.
AB  - Newly available longitudinal survey data show that people who lacked health
      insurance in 2013 and gained coverage through Medicaid or the Marketplaces in
      2014 were far more likely to obtain a usual source of care and receive preventive
      care services than their counterparts who remained uninsured in 2014.

PMID- 27702957
TI  - In The Affordable Care Act's Shadow: The Fate Of The Children's Health Insurance
      Program.
AB  - The Children's Health Insurance Program (CHIP) is a success story. CHIP has
      contributed greatly to ensuring affordable insurance and access to medical
      services for millions of children. The 2015 two-year extension of CHIP funding
      appeared to confirm its longstanding status as a bipartisan program. Yet that
      appearance obscures important changes in CHIP politics. In recent years, there
      have been calls to end the program, and its bipartisan coalition has frayed. In
      this article we analyze CHIP's funding extension, explore its shifting political
      environment, and discuss the implications for the program's future.

PMID- 27702958
TI  - Marketplace Plans With Narrow Physician Networks Feature Lower Monthly Premiums
      Than Plans With Larger Networks.
AB  - The introduction of health insurance Marketplaces under the Affordable Care Act
      has been associated with growth of restricted provider networks. The value of
      this plan design strategy, including its association with lower premiums, is
      uncertain. We used data from all silver plans offered in the 2014 health
      insurance exchanges in the fifty states and the District of Columbia to estimate
      the association between the breadth of a provider network and plan premiums. We
      found that within a market, for plans of otherwise equivalent design and
      controlling for issuer-specific pricing strategy, a plan with an extra-small
      network had a monthly premium that was 6.7 percent less expensive than that of a
      plan with a large network. Because narrow networks remain an important strategy
      available to insurance companies to offer lower-cost plans on health insurance
      Marketplaces, the success of health insurance coverage expansions may be tied to
      the successful implementation of narrow networks.

PMID- 27702959
TI  - ACOs Holding Commercial Contracts Are Larger And More Efficient Than
      Noncommercial ACOs.
AB  - Accountable care organizations (ACOs) have diverse contracting arrangements and
      have displayed wide variation in their performance. Using data from national
      surveys of 399 ACOs, we examined differences between the 228 commercial ACOs
      (those with commercial payer contracts) and the 171 noncommercial ACOs (those
      with only public contracts, such as with Medicare or Medicaid). Commercial ACOs
      were significantly larger and more integrated with hospitals, and had lower
      benchmark expenditures and higher quality scores, compared to noncommercial ACOs.
      Among all of the ACOs, there was low uptake of quality and efficiency activities.
      However, commercial ACOs reported more use of disease monitoring tools, patient
      satisfaction data, and quality improvement methods than did noncommercial ACOs.
      Few ACOs reported having high-level performance monitoring capabilities. About
      two-thirds of the ACOs had established processes for distributing any savings
      accrued, and these ACOs allocated approximately the same amount of savings to the
      ACOs themselves, participating member organizations, and physicians. Our findings
      demonstrate that ACO delivery systems remain at a nascent stage. Structural
      differences between commercial and noncommercial ACOs are important factors to
      consider as public policy efforts continue to evolve.

PMID- 27702960
TI  - State Regulation Of Freestanding Emergency Departments Varies Widely, Affecting
      Location, Growth, And Services Provided.
AB  - Freestanding emergency departments (EDs), which offer emergency medical care at
      sites separate from hospitals, are a rapidly growing alternative to traditional
      hospital-based EDs. We evaluated state regulations of freestanding EDs and
      describe their effect on the EDs' location, staffing, and services. As of
      December 2015, thirty-two states collectively had 400 freestanding EDs. Twenty
      one states had regulations that allowed freestanding EDs, and twenty-nine states
      did not have regulations that applied specifically to such EDs (one state had
      hospital regulations that precluded them). State policies regarding freestanding
      EDs varied widely, with no standard requirements for location, staffing patterns,
      or clinical capabilities. States requiring freestanding EDs to have a certificate
      of need had fewer of such EDs per capita than states without such a requirement.
      For patients to better understand the capabilities and costs of freestanding EDs
      and to be able to choose the most appropriate site of emergency care, consistent
      state regulation of freestanding EDs is needed.

PMID- 27702962
TI  - Mandatory Provider Review And Pain Clinic Laws Reduce The Amounts Of Opioids
      Prescribed And Overdose Death Rates.
AB  - To address the opioid overdose epidemic in the United States, states have
      implemented policies to reduce inappropriate opioid prescribing. These policies
      could affect the coincident heroin overdose epidemic by either driving the
      substitution of heroin for opioids or reducing simultaneous use of both
      substances. We used IMS Health's National Prescription Audit and government
      mortality data to examine the effect of these policies on opioid prescribing and
      on prescription opioid and heroin overdose death rates in the United States
      during 2006-13. The analysis revealed that combined implementation of mandated
      provider review of state-run prescription drug monitoring program data and pain
      clinic laws reduced opioid amounts prescribed by 8 percent and prescription
      opioid overdose death rates by 12 percent. We also observed relatively large but
      statistically insignificant reductions in heroin overdose death rates after
      implementation of these policies. This combination of policies was effective, but
      broader approaches to address these coincident epidemics are needed.

PMID- 27702961
TI  - Rethinking Thirty-Day Hospital Readmissions: Shorter Intervals Might Be Better
      Indicators Of Quality Of Care.
AB  - Public reporting and payment programs in the United States have embraced thirty
      day readmissions as an indicator of between-hospital variation in the quality of
      care, despite limited evidence supporting this interval. We examined risk
      standardized thirty-day risk of unplanned inpatient readmission at the hospital
      level for Medicare patients ages sixty-five and older in four states and for
      three conditions: acute myocardial infarction, heart failure, and pneumonia. The
      hospital-level quality signal captured in readmission risk was highest on the
      first day after discharge and declined rapidly until it reached a nadir at seven
      days, as indicated by a decreasing intracluster correlation coefficient. Similar
      patterns were seen across states and diagnoses. The rapid decay in the quality
      signal suggests that most readmissions after the seventh day postdischarge were
      explained by community- and household-level factors beyond hospitals' control.
      Shorter intervals of seven or fewer days might improve the accuracy and equity of
      readmissions as a measure of hospital quality for public accountability.

PMID- 27702963
TI  - Controlled Substance Lock-In Programs: Examining An Unintended Consequence Of A
      Prescription Drug Abuse Policy.
AB  - Controlled substance lock-in programs are garnering increased attention from
      payers and policy makers seeking to combat the epidemic of opioid misuse. These
      programs require high-risk patients to visit a single prescriber and pharmacy for
      coverage of controlled substance medication services. Despite high prevalence of
      the programs in Medicaid, we know little about their effects on patients'
      behavior and outcomes aside from reducing controlled substance-related claims.
      Our study was the first rigorous investigation of lock-in programs' effects on
      out-of-pocket controlled substance prescription fills, which circumvent the
      programs' restrictions and mitigate their potential public health benefits. We
      linked claims data and prescription drug monitoring program data for the period
      2009-12 for 1,647 enrollees in North Carolina Medicaid's lock-in program and
      found that enrollment was associated with a roughly fourfold increase in the
      likelihood and frequency of out-of-pocket controlled substance prescription
      fills. This finding illuminates weaknesses of lock-in programs and highlights the
      need for further scrutiny of the appropriate role, optimal design, and potential
      unintended consequences of the programs as tools to prevent opioid abuse.

PMID- 27702964
TI  - New Hepatitis C Drugs Are Very Costly And Unavailable To Many State Prisoners.
AB  - Prisoners bear much of the burden of the hepatitis C epidemic in the United
      States. Yet little is known about the scope and cost of treating hepatitis C in
      state prisons-particularly since the release of direct-acting antiviral
      medications. In the forty-one states whose departments of corrections reported
      data, 106,266 inmates (10 percent of their prisoners) were known to have
      hepatitis C on or about January 1, 2015. Only 949 (0.89 percent) of those inmates
      were being treated. Prices for a twelve-week course of direct-acting antivirals
      such as sofosbuvir and the combination drug ledipasvir/sofosbuvir varied widely
      as of September 30, 2015 ($43,418-$84,000 and $44,421-$94,500, respectively).
      Numerous corrections departments received smaller discounts than other government
      agencies did. To reduce the hepatitis C epidemic, state governments should
      increase funding for treating infected inmates. State departments of corrections
      should consider collaborating with other government agencies to negotiate
      discounts with pharmaceutical companies and with qualified health care facilities
      to provide medications through the federal 340B Drug Discount Program. Helping
      inmates transition to providers in the community upon release can enhance the
      gains achieved by treating hepatitis C in prison.

PMID- 27702965
TI  - Medicare Hospice Spending Hit $15.8 Billion In 2015, Varied By Locale, Diagnosis.
AB  - Between 2007 and 2015, Medicare hospice spending rose by 52 percent, from $10.4
      billion to $15.8 billion. The rise was driven primarily by an increase in the
      number of patients in hospice care. Medicare spending on hospice care was $642
      million, or 4.2 percent, higher in 2015 than it was in 2014. Spending and
      spending growth varied by geographic region and diagnosis.

PMID- 27702966
TI  - The Importance Of Being.
AB  - Good patient care is found not on a computer screen but in being truly present
      with patients.

PMID- 27702967
TI  - Foundation Grants To Learn About And Improve Medicaid.

PMID- 27702969
TI  - The Mental Health Workforce.

PMID- 27702970
TI  - Shortage Of Mental Health Professionals.

PMID- 27702971
TI  - Providing Mental Health Care: The Author Replies.

PMID- 27702972
TI  - Increased Use Of Care With Retail Clinics.

PMID- 27702973
TI  - Care At Retail Clinics: The Author Replies.

PMID- 27702974
TI  - Antimicrobial Resistance And New Antibiotics.

PMID- 27702976
TI  - Medicare Recipients' Use Of Medical Marijuana.

PMID- 27702975
TI  - Antimicrobial Resistance: The Authors Reply.

PMID- 27702977
TI  - US Emergency Department Death Rates.

PMID- 27702978
TI  - Medical Marijuana Laws: The Authors Reply.

PMID- 27702979
TI  - Emergency Department Death Rates: The Authors Reply.

PMID- 27702980
TI  - Faith-Based Resources And Suicide Prevention.

PMID- 27702981
TI  - Applying The Hospice Model To Advanced Illness Care.

PMID- 27702983
TI  - Errata.

PMID- 27702982
TI  - Fee-For-Service And Provider Productivity.

PMID- 27702984
TI  - The Role of Interaction Patterns with Hybrid Electric Vehicle Eco-Features for
      Drivers' Eco-Driving Performance.
AB  - OBJECTIVE: The objective of the present research was to understand drivers'
      interaction patterns with hybrid electric vehicles' (HEV) eco-features (electric
      propulsion, regenerative braking, neutral mode) and their relationship to fuel
      efficiency and driver characteristics (technical system knowledge, eco-driving
      motivation). BACKGROUND: Eco-driving (driving behaviors performed to achieve
      higher fuel efficiency) has the potential to reduce CO2 emissions caused by road
      vehicles. Eco-driving in HEVs is particularly challenging due to the systems'
      dynamic energy flows. As a result, drivers are likely to show diverse eco-driving
      behaviors, depending on factors like knowledge and motivation. The eco-features
      represent an interface for the control of the systems' energy flows. METHOD: A
      sample of 121 HEV drivers who had constantly logged their fuel consumption prior
      to the study participated in an online questionnaire. RESULTS: Drivers'
      interaction patterns with the eco-features were related to fuel efficiency. A
      common factor was identified in an exploratory factor analysis, characterizing
      the intensity of actively dealing with electric energy, which was also related to
      fuel efficiency. Driver characteristics were not related to this factor, yet they
      were significant predictors of fuel efficiency. CONCLUSION: From the perspective
      of user-energy interaction, the relationship of the aggregated factor to fuel
      efficiency emphasizes the central role of drivers' perception of and interaction
      with energy conversions in determining HEV eco-driving success. APPLICATION: To
      arrive at an in-depth understanding of drivers' eco-driving behaviors that can
      guide interface design, authors of future research should be concerned with the
      psychological processes that underlie drivers' interaction patterns with eco
      features.

PMID- 27702985
TI  - Cancer-specific mutations in p53 induce the translation of Delta160p53 promoting
      tumorigenesis.
AB  - Wild-type p53 functions as a tumour suppressor while mutant p53 possesses
      oncogenic potential. Until now it remains unclear how a single mutation can
      transform p53 into a functionally distinct gene harbouring a new set of original
      cellular roles. Here we show that the most common p53 cancer mutants express a
      larger number and higher levels of shorter p53 protein isoforms that are
      translated from the mutated full-length p53 mRNA. Cells expressing mutant p53
      exhibit "gain-of-function" cancer phenotypes, such as enhanced cell survival,
      proliferation, invasion and adhesion, altered mammary tissue architecture and
      invasive cell structures. Interestingly, Delta160p53-overexpressing cells behave
      in a similar manner. In contrast, an exogenous or endogenous mutant p53 that
      fails to express Delta160p53 due to specific mutations or antisense knock-down
      loses pro-oncogenic potential. Our data support a model in which "gain-of
      function" phenotypes induced by p53 mutations depend on the shorter p53 isoforms.
      As a conserved wild-type isoform, Delta160p53 has evolved during millions of
      years. We thus provide a rational explanation for the origin of the tumour
      promoting functions of p53 mutations.

PMID- 27702986
TI  - Gadd45a is a heterochromatin relaxer that enhances iPS cell generation.
AB  - Reprogramming of somatic cells to induced pluripotent stem cells rewrites the
      code of cell fate at the chromatin level. Yet, little is known about this process
      physically. Here, we describe a fluorescence recovery after photobleaching method
      to assess the dynamics of heterochromatin/euchromatin and show significant
      heterochromatin loosening at the initial stage of reprogramming. We identify
      growth arrest and DNA damage-inducible protein a (Gadd45a) as a chromatin relaxer
      in mouse embryonic fibroblasts, which also enhances somatic cell reprogramming
      efficiency. We show that residue glycine 39 (G39) in Gadd45a is essential for
      interacting with core histones, opening chromatin and enhancing reprogramming. We
      further demonstrate that Gadd45a destabilizes histone-DNA interactions and
      facilitates the binding of Yamanaka factors to their targets for activation. Our
      study provides a method to screen factors that impact on chromatin structure in
      live cells, and identifies Gadd45a as a chromatin relaxer.

PMID- 27702987
TI  - Linear ubiquitination by LUBEL has a role in Drosophila heat stress response.
AB  - The HOIP ubiquitin E3 ligase generates linear ubiquitin chains by forming a
      complex with HOIL-1L and SHARPIN in mammals. Here, we provide the first evidence
      of linear ubiquitination induced by a HOIP orthologue in Drosophila We identify
      Drosophila CG11321, which we named Linear Ubiquitin E3 ligase (LUBEL), and find
      that it catalyzes linear ubiquitination in vitro We detect endogenous linear
      ubiquitin chain-derived peptides by mass spectrometry in Drosophila Schneider 2
      cells and adult flies. Furthermore, using CRISPR/Cas9 technology, we establish
      linear ubiquitination-defective flies by mutating residues essential for the
      catalytic activity of LUBEL Linear ubiquitination signals accumulate upon heat
      shock in flies. Interestingly, flies with LUBEL mutations display reduced
      survival and climbing defects upon heat shock, which is also observed upon
      specific LUBEL depletion in muscle. Thus, LUBEL is involved in the heat response
      by controlling linear ubiquitination in flies.

PMID- 27702990
TI  - Dying to live: cell elimination as a developmental strategy in angiosperm seeds.
AB  - The complete elimination of unwanted cells during development is a repeated theme
      in both multicellular animals and in plants. In plants, such events have been
      extensively studied and reviewed in terms of their molecular regulation, of
      marker genes and proteins expressed, and in terms of cellular changes associated
      with their progression. This review will take a slightly different view of
      developmental cell elimination and will concentrate specifically on the numerous
      elimination events that occur during ovule and seed development (here grouped
      together as seed development). It asks why this cell elimination occurs in
      specific seed tissues, in order to understand something about the commonalities
      underlying how seemingly disparate events are triggered and regulated. Finally,
      by placing the seed in its broader evolutionary context, the question of why cell
      elimination may have emerged as such a key component of the seed developmental
      toolbox will be considered.

PMID- 27702989
TI  - Rhizosecretion of stele-synthesized glucosinolates and their catabolites requires
      GTR-mediated import in Arabidopsis.
AB  - Casparian strip-generated apoplastic barriers not only control the radial flow of
      both water and ions but may also constitute a hindrance for the rhizosecretion of
      stele-synthesized phytochemicals. Here, we establish root-synthesized
      glucosinolates (GLS) are in Arabidopsis as a model to study the transport routes
      of plant-derived metabolites from the site of synthesis to the rhizosphere.
      Analysing the expression of GLS synthetic genes in the root indicate that the
      stele is the major site for the synthesis of aliphatic GLS, whereas indole GLS
      can be synthesized in both the stele and the cortex. Sampling root exudates from
      the wild type and the double mutant of the GLS importers GTR1 and GTR2 show that
      GTR-mediated retention of stele-synthesized GLS is a prerequisite for the
      exudation of both intact GLS and their catabolites into the rhizosphere. The
      expression of the GTRs inside the stele, combined with the previous observation
      that GLS are exported from biosynthetic cells, suggest three possible routes of
      stele-synthesized aliphatic GLS after their synthesis: (i) GTR-dependent import
      to cells symplastically connected to the cortical cells and the rhizosphere; (ii)
      GTR-independent transport via the xylem to the shoot; and (iii) GTR-dependent
      import to GLS-degrading myrosin cells at the cortex. The study suggests a
      previously undiscovered role of the import process in the rhizosecretion of root
      synthesized phytochemicals.

PMID- 27702991
TI  - The influence of leaf anatomy on the internal light environment and
      photosynthetic electron transport rate: exploration with a new leaf ray tracing
      model.
AB  - Leaf photosynthesis is determined by biochemical properties and anatomical
      features. Here we developed a three-dimensional leaf model that can be used to
      evaluate the internal light environment of a leaf and its implications for whole
      leaf electron transport rates (J). This model includes (i) the basic components
      of a leaf, such as the epidermis, palisade and spongy tissues, as well as the
      physical dimensions and arrangements of cell walls, vacuoles and chloroplasts;
      and (ii) an efficient forward ray-tracing algorithm, predicting the internal
      light environment for light of wavelengths between 400 and 2500nm. We studied the
      influence of leaf anatomy and ambient light on internal light conditions and J
      The results show that (i) different chloroplasts can experience drastically
      different light conditions, even when they are located at the same distance from
      the leaf surface; (ii) bundle sheath extensions, which are strips of parenchyma,
      collenchyma or sclerenchyma cells connecting the vascular bundles with the
      epidermis, can influence photosynthetic light-use efficiency of leaves; and (iii)
      chloroplast positioning can also influence the light-use efficiency of leaves.
      Mechanisms underlying leaf internal light heterogeneity and implications of the
      heterogeneity for photoprotection and for the convexity of the light response
      curves are discussed.

PMID- 27702993
TI  - Redefining 'stress resistance genes', and why it matters.

PMID- 27702988
TI  - Drugging the addict: non-oncogene addiction as a target for cancer therapy.
AB  - Historically, cancers have been treated with chemotherapeutics aimed to have
      profound effects on tumor cells with only limited effects on normal tissue. This
      approach was followed by the development of small-molecule inhibitors that can
      target oncogenic pathways critical for the survival of tumor cells. The clinical
      targeting of these so-called oncogene addictions, however, is in many instances
      hampered by the outgrowth of resistant clones. More recently, the proper
      functioning of non-mutated genes has been shown to enhance the survival of many
      cancers, a phenomenon called non-oncogene addiction. In the current review, we
      will focus on the distinct non-oncogenic addictions found in cancer cells,
      including synthetic lethal interactions, the underlying stress phenotypes, and
      arising therapeutic opportunities.

PMID- 27702992
TI  - A stilbene synthase allele from a Chinese wild grapevine confers resistance to
      powdery mildew by recruiting salicylic acid signalling for efficient defence.
AB  - Stilbenes are central phytoalexins in Vitis, and induction of the key enzyme
      stilbene synthase (STS) is pivotal for disease resistance. Here, we address the
      potential for breeding resistance using an STS allele isolated from Chinese wild
      grapevine Vitis pseudoreticulata (VpSTS) by comparison with its homologue from
      Vitis vinifera cv. 'Carigane' (VvSTS). Although the coding regions of both
      alleles are very similar (>99% identity on the amino acid level), the promoter
      regions are significantly different. By expression in Arabidopsis as a
      heterologous system, we show that the allele from the wild Chinese grapevine can
      confer accumulation of stilbenes and resistance against the powdery mildew
      Golovinomyces cichoracearum, whereas the allele from the vinifera cultivar
      cannot. To dissect the upstream signalling driving the activation of this
      promoter, we used a dual-luciferase reporter system in a grapevine cell culture.
      We show elevated responsiveness of the promoter from the wild grape to salicylic
      acid (SA) and to the pathogen-associated molecular pattern (PAMP) flg22, equal
      induction of both alleles by jasmonic acid (JA), and a lack of response to the
      cell death-inducing elicitor Harpin. This elevated SA response of the VpSTS
      promoter depends on calcium influx, oxidative burst by RboH, mitogen-activated
      protein kinase (MAPK) signalling, and JA synthesis. We integrate the data in the
      context of a model where the resistance of V. pseudoreticulata is linked to a
      more efficient recruitment of SA signalling for phytoalexin synthesis.

PMID- 27702995
TI  - A rhamnose-deficient lipopolysaccharide mutant of Rhizobium sp. IRBG74 is
      defective in root colonization and beneficial interactions with its flooding
      tolerant hosts Sesbania cannabina and wetland rice.
AB  - Rhizobium sp. IRBG74 develops a classical nitrogen-fixing symbiosis with the
      aquatic legume Sesbania cannabina (Retz.). It also promotes the growth of wetland
      rice (Oryza sativa L.), but little is known about the rhizobial determinants
      important for these interactions. In this study, we analyzed the colonization of
      S. cannabina and rice using a strain of Rhizobium sp. IRBG74 dually marked with
      beta-glucuronidase and the green fluorescent protein. This bacterium colonized S.
      cannabina by crack entry and through root hair infection under flooded and non
      flooded conditions, respectively. Rhizobium sp. IRBG74 colonized the surfaces of
      wetland rice roots, but also entered them at the base of lateral roots. It became
      endophytically established within intercellular spaces in the rice cortex, and
      intracellularly within epidermal and hypodermal cells. A mutant of Rhizobium sp.
      IRBG74 altered in the synthesis of the rhamnose-containing O-antigen exhibited
      significant defects, not only in nodulation and symbiotic nitrogen fixation with
      S. cannabina, but also in rice colonization and plant growth promotion.
      Supplementation with purified lipopolysaccharides from the wild-type strain, but
      not from the mutant, restored the beneficial colonization of rice roots, but not
      fully effective nodulation of S. cannabina Commonalities and differences in the
      rhizobial colonization of the roots of wetland legume and rice hosts are
      discussed.

PMID- 27702994
TI  - The build-up of osmotic stress responses within the growing root apex using
      kinematics and RNA-sequencing.
AB  - Molecular regulation of growth must include spatial and temporal coupling of cell
      production and cell expansion. The underlying mechanisms, especially under
      environmental challenge, remain obscure. Spatial patterns of cell processes make
      the root apex well suited to deciphering stress signaling pathways, and to
      investigating both processes. Kinematics and RNA-sequencing were used to analyze
      the immediate growth response of hydroponically grown Populus nigra cuttings
      submitted to osmotic stress. About 7400 genes and unannotated transcriptionally
      active regions were differentially expressed between the division and elongation
      zones. Following the onset of stress, growth decreased sharply, probably due to
      mechanical effects, before recovering partially. Stress impaired cell expansion
      over the apex, progressively shortened the elongation zone, and reduced the cell
      production rate. Changes in gene expression revealed that growth reduction was
      mediated by a shift in hormone homeostasis. Osmotic stress rapidly elicited
      auxin, ethylene, and abscisic acid. When growth restabilized, transcriptome
      remodeling became complex and zone specific, with the deployment of hormone
      signaling cascades, transcriptional regulators, and stress-responsive genes. Most
      transcriptional regulations fit growth reduction, but stress also promoted
      expression of some growth effectors, including aquaporins and expansins Together,
      osmotic stress interfered with growth by activating regulatory proteins rather
      than by repressing the machinery of expansive growth.

PMID- 27702996
TI  - Effects of reduced carbonic anhydrase activity on CO2 assimilation rates in
      Setaria viridis: a transgenic analysis.
AB  - In C4 species, the major beta-carbonic anhydrase (beta-CA) localized in the
      mesophyll cytosol catalyses the hydration of CO2 to HCO3-, which
      phosphoenolpyruvate carboxylase uses in the first step of C4 photosynthesis. To
      address the role of CA in C4 photosynthesis, we generated transgenic Setaria
      viridis depleted in beta-CA. Independent lines were identified with as little as
      13% of wild-type CA. No photosynthetic defect was observed in the transformed
      lines at ambient CO2 partial pressure (pCO2). At low pCO2, a strong correlation
      between CO2 assimilation rates and CA hydration rates was observed. C18O16O
      isotope discrimination was used to estimate the mesophyll conductance to CO2
      diffusion from the intercellular air space to the mesophyll cytosol (gm) in
      control plants, which allowed us to calculate CA activities in the mesophyll
      cytosol (Cm). This revealed a strong relationship between the initial slope of
      the response of the CO2 assimilation rate to cytosolic pCO2 (ACm) and cytosolic
      CA activity. However, the relationship between the initial slope of the response
      of CO2 assimilation to intercellular pCO2 (ACi) and cytosolic CA activity was
      curvilinear. This indicated that in S. viridis, mesophyll conductance may be a
      contributing limiting factor alongside CA activity to CO2 assimilation rates at
      low pCO2.

PMID- 27702997
TI  - Dynamic changes of small RNAs in rice spikelet development reveal specialized
      reproductive phasiRNA pathways.
AB  - Dissection of the genetic pathways and mechanisms by which anther development
      occurs in grasses is crucial for both a basic understanding of plant development
      and for examining traits of agronomic importance such as male sterility. In rice,
      MULTIPLE SPOROCYTES1 (MSP1), a leucine-rich-repeat receptor kinase, plays an
      important role in anther development by limiting the number of sporocytes.
      OsTDL1a (a TPD1-like gene in rice) encodes a small protein that acts as a
      cofactor of MSP1 in the same regulatory pathway. In this study, we analyzed small
      RNA and mRNA changes in different stages of spikelets from wild-type rice, and
      from msp1 and ostdl1a mutants. Analysis of the small RNA data identified miRNAs
      demonstrating differential abundances. miR2275 was depleted in the two rice
      mutants; this miRNA is specifically enriched in anthers and functions to trigger
      the production of 24-nt phased secondary siRNAs (phasiRNAs) from PHAS loci. We
      observed that the 24-nt phasiRNAs as well as their precursor PHAS mRNAs were also
      depleted in the two mutants. An analysis of co-expression identified three
      Argonaute-encoding genes (OsAGO1d, OsAGO2b, and OsAGO18) that accumulate
      transcripts coordinately with phasiRNAs, suggesting a functional relationship. By
      mRNA in situ analysis, we demonstrated a strong correlation between the
      spatiotemporal pattern of these OsAGO transcripts and phasiRNA accumulations.

PMID- 27702998
TI  - Identification of Neutrophil Exocytosis Inhibitors (Nexinhibs), Small Molecule
      Inhibitors of Neutrophil Exocytosis and Inflammation: DRUGGABILITY OF THE SMALL
      GTPase Rab27a.
AB  - Neutrophils constitute the first line of cellular defense in response to
      bacterial and fungal infections and rely on granular proteins to kill
      microorganisms, but uncontrolled secretion of neutrophil cargos is injurious to
      the host and should be closely regulated. Thus, increased plasma levels of
      neutrophil secretory proteins, including myeloperoxidase and elastase, are
      associated with tissue damage and are hallmarks of systemic inflammation. Here,
      we describe a novel high-throughput screening approach to identify small molecule
      inhibitors of the interaction between the small GTPase Rab27a and its effector
      JFC1, two central regulators of neutrophil exocytosis. Using this assay, we have
      identified small molecule inhibitors of Rab27a-JFC1 binding that were also active
      in cell-based neutrophil-specific exocytosis assays, demonstrating the
      druggability of Rab GTPases and their effectors. These compounds, named Nexinhibs
      (neutrophil exocytosis inhibitors), inhibit exocytosis of azurophilic granules in
      human neutrophils without affecting other important innate immune responses,
      including phagocytosis and neutrophil extracellular trap production. Furthermore,
      the compounds are reversible and potent inhibitors of the extracellular
      production of superoxide anion by preventing the up-regulation of the granule
      membrane-associated subunit of the NADPH oxidase at the plasma membrane.
      Nexinhibs also inhibit the up-regulation of activation signature molecules,
      including the adhesion molecules CD11b and CD66b. Importantly, by using a mouse
      model of endotoxin-induced systemic inflammation, we show that these inhibitors
      have significant activity in vivo manifested by decreased plasma levels of
      neutrophil secretory proteins and significantly decreased tissue infiltration by
      inflammatory neutrophils. Altogether, our data present the first neutrophil
      exocytosis-specific inhibitor with in vivo anti-inflammatory activity, supporting
      its potential use as an inhibitor of systemic inflammation.

PMID- 27702999
TI  - Ohgata, the Single Drosophila Ortholog of Human Cereblon, Regulates Insulin
      Signaling-dependent Organismic Growth.
AB  - Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that
      is highly conserved in animals and plants. CRBN proteins have been implicated in
      various biological processes such as development, metabolism, learning, and
      memory formation, and their impairment has been linked to autosomal recessive non
      syndromic intellectual disability and cancer. Furthermore, human CRBN was
      identified as the primary target of thalidomide teratogenicity. Data on
      functional analysis of CRBN family members in vivo, however, are still scarce.
      Here we identify Ohgata (OHGT), the Drosophila ortholog of CRBN, as a regulator
      of insulin signaling-mediated growth. Using ohgt mutants that we generated by
      targeted mutagenesis, we show that its loss results in increased body weight and
      organ size without changes of the body proportions. We demonstrate that ohgt
      knockdown in the fat body, an organ analogous to mammalian liver and adipose
      tissue, phenocopies the growth phenotypes. We further show that overgrowth is due
      to an elevation of insulin signaling in ohgt mutants and to the down-regulation
      of inhibitory cofactors of circulating Drosophila insulin-like peptides (DILPs),
      named acid-labile subunit and imaginal morphogenesis protein-late 2. The two
      inhibitory proteins were previously shown to be components of a heterotrimeric
      complex with growth-promoting DILP2 and DILP5. Our study reveals OHGT as a novel
      regulator of insulin-dependent organismic growth in Drosophila.

PMID- 27703000
TI  - Palmitoylation of Desmoglein 2 Is a Regulator of Assembly Dynamics and Protein
      Turnover.
AB  - Desmosomes are prominent adhesive junctions present between many epithelial cells
      as well as cardiomyocytes. The mechanisms controlling desmosome assembly and
      remodeling in epithelial and cardiac tissue are poorly understood. We recently
      identified protein palmitoylation as a mechanism regulating desmosome dynamics.
      In this study, we have focused on the palmitoylation of the desmosomal cadherin
      desmoglein-2 (Dsg2) and characterized the role that palmitoylation of Dsg2 plays
      in its localization and stability in cultured cells. We identified two cysteine
      residues in the juxtamembrane (intracellular anchor) domain of Dsg2 that, when
      mutated, eliminate its palmitoylation. These cysteine residues are conserved in
      all four desmoglein family members. Although mutant Dsg2 localizes to endogenous
      desmosomes, there is a significant delay in its incorporation into junctions, and
      the mutant is also present in a cytoplasmic pool. Triton X-100 solubility assays
      demonstrate that mutant Dsg2 is more soluble than wild-type protein.
      Interestingly, trafficking of the mutant Dsg2 to the cell surface was delayed,
      and a pool of the non-palmitoylated Dsg2 co-localized with lysosomal markers.
      Taken together, these data suggest that palmitoylation of Dsg2 regulates protein
      transport to the plasma membrane. Modulation of the palmitoylation status of
      desmosomal cadherins can affect desmosome dynamics.

PMID- 27703001
TI  - Different DNA End Configurations Dictate Which NHEJ Components Are Most Important
      for Joining Efficiency.
AB  - The nonhomologous DNA end-joining (NHEJ) pathway is a key mechanism for repairing
      dsDNA breaks that occur often in eukaryotic cells. In the simplest model, these
      breaks are first recognized by Ku, which then interacts with other NHEJ proteins
      to improve their affinity at DNA ends. These include DNA-PKcs and Artemis for
      trimming the DNA ends; DNA polymerase MU and lambda to add nucleotides; and the
      DNA ligase IV complex to ligate the ends with the additional factors, XRCC4 (X
      ray repair cross-complementing protein 4), XLF (XRCC4-like factor/Cernunos), and
      PAXX (paralog of XRCC4 and XLF). In vivo studies have demonstrated the degrees of
      importance of these NHEJ proteins in the mechanism of repair of dsDNA breaks, but
      interpretations can be confounded by other cellular processes. In vitro studies
      with NHEJ proteins have been performed to evaluate the nucleolytic resection,
      polymerization, and ligation steps, but a complete system has been elusive. Here
      we have developed a NHEJ reconstitution system that includes the nuclease,
      polymerase, and ligase components to evaluate relative NHEJ efficiency and
      analyze ligated junctional sequences for various types of DNA ends, including
      blunt, 5' overhangs, and 3' overhangs. We find that different dsDNA end
      structures have differential dependence on these enzymatic components. The
      dependence of some end joining on only Ku and XRCC4.DNA ligase IV allows us to
      formulate a physical model that incorporates nuclease and polymerase components
      as needed.

PMID- 27703002
TI  - Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization
      through Glycolysis.
AB  - The Wnt signaling pathway is critical for a number of functions in the central
      nervous system, including regulation of the synaptic cleft structure and
      neuroprotection against injury. Deregulation of Wnt signaling has been associated
      with several brain pathologies, including Alzheimer's disease. In recent years,
      it has been suggested that the Wnt pathway might act as a central integrator of
      metabolic signals from peripheral organs to the brain, which would represent a
      new role for Wnt signaling in cell metabolism. Energy metabolism is critical for
      normal neuronal function, which mainly depends on glucose utilization. Brain
      energy metabolism is important in almost all neurological disorders, to which a
      decrease in the capacity of the brain to utilize glucose has been linked.
      However, little is known about the relationship between Wnt signaling and
      neuronal glucose metabolism in the cellular context. In the present study, we
      found that acute treatment with the Wnt3a ligand induced a large increase in
      glucose uptake, without changes in the expression or localization of glucose
      transporter type 3. In addition, we observed that Wnt3a treatment increased the
      activation of the metabolic sensor Akt. Moreover, we observed an increase in the
      activity of hexokinase and in the glycolytic rate, and both processes were
      dependent on activation of the Akt pathway. Furthermore, we did not observe
      changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose
      phosphate pathway. The effect of Wnt3a was independent of both the transcription
      of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest
      that Wnt signaling stimulates glucose utilization in cortical neurons through
      glycolysis to satisfy the high energy demand of these cells.

PMID- 27703003
TI  - SUMO Modification Reverses Inhibitory Effects of Smad Nuclear Interacting Protein
      1 in TGF-beta Responses.
AB  - SNIP1 (Smad nuclear interacting protein 1) is a transcription repressor for the
      TGF-beta and NF-kappaB signaling pathways through disrupting the recruitment of
      co-activator p300. However, it is unclear how the functions of SNIP1 in the TGF
      beta signaling pathway are controlled. Our present studies show that SNIP1 is
      covalently modified by small ubiquitin-like modifier (SUMO) in vitro and in vivo
      at three lysine sites: Lys5, Lys30, and Lys108, with Lys30 being the major SUMO
      modification site. SUMOylation of SNIP1 is enhanced by SUMO E3 ligase PIAS
      proteins and inhibited by SUMO proteases SENP1/2. Furthermore, we find that
      SUMOylation of SNIP1 attenuates its inhibitory effect in TGF-beta signaling
      because the SUMO-conjugated form of SNIP1 exhibits impaired ability to disrupt
      the formation of Smad complex and the interaction between p300 and Smads.
      Subsequently, SUMOylation of SNIP1 leads to the loss of SNIP1-mediated inhibition
      on expression of the TGF-beta target genes PAI-1 and MMP2 and eventually enhances
      TGF-beta-regulated cell migration and invasion.

PMID- 27703004
TI  - Quantitative Proteomics of the SMAD (Suppressor of Mothers against
      Decapentaplegic) Transcription Factor Family Identifies Importin 5 as a Bone
      Morphogenic Protein Receptor SMAD-specific Importin.
AB  - Gene-specific transcription factors (GSTFs) control gene transcription by DNA
      binding and specific protein complex recruitment, which regulates promoter
      accessibility for transcription initiation by RNA polymerase II. Mutations in the
      GSTFs Suppressor of Mothers Against Decapentaplegic 2 (SMAD2) and SMAD4 are
      frequently associated with colon and rectal carcinomas. These proteins play an
      important role in bone morphogenic protein (BMP) and transforming growth factor
      beta (TGF-beta) signaling pathways controlling cell fate and proliferation. To
      study the protein interactome of the SMAD protein family we generated a
      quantitative proteomics pipeline that allows for inducible expression of GFP
      tagged SMAD proteins followed by affinity purification and quantitative mass
      spectrometry analysis. Data are available via ProteomeXchange with identifier
      PXD004529. The nuclear importin IPO5 was identified as a novel interacting
      protein of SMAD1. Overexpression of IPO5 in various cell lines specifically
      increases nuclear localization of BMP receptor-activated SMADs (R-SMADs)
      confirming a functional relationship between IPO5 and BMP but not TGF-beta R
      SMADs. Finally, we provide evidence that variation in length of the lysine
      stretch of the nuclear localization sequence is a determinant for importin
      specificity.

PMID- 27703005
TI  - The R838S Mutation in Retinal Guanylyl Cyclase 1 (RetGC1) Alters Calcium
      Sensitivity of cGMP Synthesis in the Retina and Causes Blindness in Transgenic
      Mice.
AB  - Substitutions of Arg838 in the dimerization domain of a human retinal membrane
      guanylyl cyclase 1 (RetGC1) linked to autosomal dominant cone-rod degeneration
      type 6 (CORD6) change RetGC1 regulation in vitro by Ca2+ In addition, we find
      that R838S substitution makes RetGC1 less sensitive to inhibition by retinal
      degeneration-3 protein (RD3). We selectively expressed human R838S RetGC1 in
      mouse rods and documented the decline in rod vision and rod survival. To verify
      that changes in rods were specifically caused by the CORD6 mutation, we used for
      comparison cones, which in the same mice did not express R838S RetGC1 from the
      transgenic construct. The R838S RetGC1 expression in rod outer segments reduced
      inhibition of cGMP production in the transgenic mouse retinas at the free calcium
      concentrations typical for dark-adapted rods. The transgenic mice demonstrated
      early-onset and rapidly progressed with age decline in visual responses from the
      targeted rods, in contrast to the longer lasting preservation of function in the
      non-targeted cones. The decline in rod function in the retina resulted from a
      progressive degeneration of rods between 1 and 6 months of age, with the severity
      and pace of the degeneration consistent with the extent to which the Ca2+
      sensitivity of the retinal cGMP production was affected. Our study presents a new
      experimental model for exploring cellular mechanisms of the CORD6-related
      photoreceptor death. This mouse model provides the first direct biochemical and
      physiological in vivo evidence for the Arg838 substitutions in RetGC1 being the
      culprit behind the pathogenesis of the CORD6 congenital blindness.

PMID- 27703007
TI  - Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling: A POTENTIAL
      ROLE FOR LIPID-PROTEIN ADDUCTS.
AB  - When inhaled, ozone (O3) interacts with cholesterols of airway epithelial cell
      membranes or the lung-lining fluid, generating chemically reactive oxysterols.
      The mechanism by which O3-derived oxysterols affect molecular function is
      unknown. Our data show that in vitro exposure of human bronchial epithelial cells
      to O3 results in the formation of oxysterols, epoxycholesterol-alpha and -beta
      and secosterol A and B (Seco A and Seco B), in cell lysates and apical washes.
      Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to
      O3 contained elevated levels of these oxysterol species. As expected, O3-derived
      oxysterols have a pro-inflammatory effect and increase NF-kappaB activity.
      Interestingly, expression of the cholesterol efflux pump ATP-binding cassette
      transporter 1 (ABCA1), which is regulated by activation of the liver X receptor
      (LXR), was suppressed in epithelial cells exposed to O3 Additionally, exposure of
      LXR knock-out mice to O3 enhanced pro-inflammatory cytokine production in the
      lung, suggesting LXR inhibits O3-induced inflammation. Using alkynyl surrogates
      of O3-derived oxysterols, our data demonstrate adduction of LXR with Seco A.
      Similarly, supplementation of epithelial cells with alkynyl-tagged cholesterol
      followed by O3 exposure causes observable lipid-LXR adduct formation. Experiments
      using Seco A and the LXR agonist T0901317 (T09) showed reduced expression of
      ABCA1 as compared with stimulation with T0901317 alone, indicating that Seco A
      LXR protein adduct formation inhibits LXR activation by traditional agonists.
      Overall, these data demonstrate that O3-derived oxysterols have pro-inflammatory
      functions and form lipid-protein adducts with LXR, thus leading to suppressed
      cholesterol regulatory gene expression and providing a biochemical mechanism
      mediating O3-derived formation of oxidized lipids in the airways and subsequent
      adverse health effects.

PMID- 27703006
TI  - Bipartite Role of Heat Shock Protein 90 (Hsp90) Keeps CRAF Kinase Poised for
      Activation.
AB  - CRAF kinase maintains cell viability, growth, and proliferation by participating
      in the MAPK pathway. Unlike BRAF, CRAF requires continuous chaperoning by Hsp90
      to retain MAPK signaling. However, the reason behind the continuous association
      of Hsp90 with CRAF is still elusive. In this study, we have identified the
      bipartite role of Hsp90 in chaperoning CRAF kinase. Hsp90 facilitates Ser-621
      phosphorylation of CRAF and prevents the kinase from degradation. Co-chaperone
      Cdc37 assists in this phosphorylation event. However, after folding, the
      stability of the kinase becomes insensitive to Hsp90 inhibition, although the
      physical association between Hsp90 and CRAF remains intact. We observed that
      overexpression of Hsp90 stimulates MAPK signaling by activating CRAF. The
      interaction between Hsp90 and CRAF is substantially increased under an elevated
      level of cellular Hsp90 and in the presence of either active Ras (RasV12) or EGF.
      Surprisingly, enhanced binding of Hsp90 to CRAF occurs prior to the Ras-CRAF
      association and facilitates actin recruitment to CRAF for efficient Ras-CRAF
      interaction, which is independent of the ATPase activity of Hsp90. However,
      monomeric CRAF (CRAFR401H) shows abrogated interaction with both Hsp90 and actin,
      thereby affecting Hsp90-dependent CRAF activation. This finding suggests that
      stringent assemblage of Hsp90 keeps CRAF kinase equipped for participating in the
      MAPK pathway. Thus, the role of Hsp90 in CRAF maturation and activation acts as a
      limiting factor to maintain the function of a strong client like CRAF kinase.

PMID- 27703008
TI  - The Role of Folate Transport in Antifolate Drug Action in Trypanosoma brucei.
AB  - The aim of this study was to identify and characterize mechanisms of resistance
      to antifolate drugs in African trypanosomes. Genome-wide RNAi library screens
      were undertaken in bloodstream form Trypanosoma brucei exposed to the antifolates
      methotrexate and raltitrexed. In conjunction with drug susceptibility and folate
      transport studies, RNAi knockdown was used to validate the functions of the
      putative folate transporters. The transport kinetics of folate and methotrexate
      were further characterized in whole cells. RNA interference target sequencing
      experiments identified a tandem array of genes encoding a folate transporter
      family, TbFT1-3, as major contributors to antifolate drug uptake. RNAi knockdown
      of TbFT1-3 substantially reduced folate transport into trypanosomes and reduced
      the parasite's susceptibly to the classical antifolates methotrexate and
      raltitrexed. In contrast, knockdown of TbFT1-3 increased susceptibly to the non
      classical antifolates pyrimethamine and nolatrexed. Both folate and methotrexate
      transport were inhibited by classical antifolates but not by non-classical
      antifolates or biopterin. Thus, TbFT1-3 mediates the uptake of folate and
      classical antifolates in trypanosomes, and TbFT1-3 loss-of-function is a
      mechanism of antifolate drug resistance.

PMID- 27703009
TI  - Epithelial Cholesterol Deficiency Attenuates Human Antigen R-linked Pro
      inflammatory Stimulation via an SREBP2-linked Circuit.
AB  - Patients with chronic intestinal ulcerative diseases, such as inflammatory bowel
      disease, tend to exhibit abnormal lipid profiles, which may affect the gut
      epithelial integrity. We hypothesized that epithelial cholesterol depletion may
      trigger inflammation-checking machinery via cholesterol sentinel signaling
      molecules whose disruption in patients may aggravate inflammation and disease
      progression. In the present study, sterol regulatory element-binding protein 2
      (SREBP2) as the cholesterol sentinel was assessed for its involvement in the
      epithelial inflammatory responses in cholesterol-depleted enterocytes. Patients
      and experimental animals with intestinal ulcerative injuries showed suppression
      in epithelial SREBP2. Moreover, SREBP2-deficient enterocytes showed enhanced pro
      inflammatory signals in response to inflammatory insults, indicating regulatory
      roles of SREBP2 in gut epithelial inflammation. However, epithelial cholesterol
      depletion transiently induced pro-inflammatory chemokine expression regardless of
      the well known pro-inflammatory nuclear factor-kappaB signals. In contrast,
      cholesterol depletion also exerts regulatory actions to maintain epithelial
      homeostasis against excessive inflammation via SREBP2-associated signals in a
      negative feedback loop. Mechanistically, SREBP2 and its induced target EGR-1 were
      positively involved in induction of peroxisome proliferator-activated receptor
      gamma (PPARgamma), a representative anti-inflammatory transcription factor. As a
      crucial target of the SREBP2-EGR-1-PPARgamma-associated signaling pathways, the
      mRNA stabilizer, human antigen R (HuR) was retained in nuclei, leading to reduced
      stability of pro-inflammatory chemokine transcripts. This mechanistic
      investigation provides clinical insights into protective roles of the epithelial
      cholesterol deficiency against excessive inflammatory responses via the SREBP2
      HuR circuit, although the deficiency triggers transient pro-inflammatory signals.

PMID- 27703010
TI  - Hepatic ZIP14-mediated Zinc Transport Contributes to Endosomal Insulin Receptor
      Trafficking and Glucose Metabolism.
AB  - Zinc influences signaling pathways through controlled targeted zinc transport.
      Zinc transporter Zip14 KO mice display a phenotype that includes impaired
      intestinal barrier function with low grade chronic inflammation,
      hyperinsulinemia, and increased body fat, which are signatures of diet-induced
      diabetes (type 2 diabetes) and obesity in humans. Hyperglycemia in type 2
      diabetes and obesity is caused by insulin resistance. Insulin resistance results
      in inhibition of glucose uptake by liver and other peripheral tissues,
      principally adipose and muscle and with concurrently higher hepatic glucose
      production. Therefore, modulation of hepatic glucose metabolism is an important
      target for antidiabetic treatment approaches. We demonstrate that during glucose
      uptake, cell surface abundance of zinc transporter ZIP14 and mediated zinc
      transport increases. Zinc is distributed to multiple sites in hepatocytes through
      sequential translocation of ZIP14 from plasma membrane to early and late
      endosomes. Endosomes from Zip14 KO mice were zinc-deficient because activities of
      the zinc-dependent insulin-degrading proteases insulin-degrading enzyme and
      cathepsin D were impaired; hence insulin receptor activity increased. Transient
      increases in cytosolic zinc levels are concurrent with glucose uptake and
      suppression of glycogen synthesis. In contrast, Zip14 KO mice exhibited greater
      hepatic glycogen synthesis and impaired gluconeogenesis and glycolysis related to
      low cytosolic zinc levels. We can conclude that ZIP14-mediated zinc transport
      contributes to regulation of endosomal insulin receptor activity and glucose
      homeostasis in hepatocytes. Therefore, modulation of ZIP14 transport activity
      presents a new target for management of diabetes and other glucose-related
      disorders.

PMID- 27703011
TI  - A Role for Ceramides, but Not Sphingomyelins, as Antagonists of Insulin Signaling
      and Mitochondrial Metabolism in C2C12 Myotubes.
AB  - The accumulation of sphingolipids in obesity leads to impairments in insulin
      sensitivity and mitochondrial metabolism, but the precise species driving these
      defects is unclear. We have modeled these obesity-induced effects in cultured
      C2C12 myotubes, using BSA-conjugated palmitate to increase synthesis of
      endogenous sphingolipids and to inhibit insulin signaling and oxidative
      phosphorylation. Palmitate (a) induced the accumulation of sphingomyelin (SM)
      precursors such as sphinganine, dihydroceramide, and ceramide; (b) inhibited
      insulin stimulation of a central modulator of anabolic metabolism, Akt/PKB; (c)
      inhibited insulin-stimulated glycogen synthesis; and (d) decreased oxygen
      consumption and ATP synthesis. Under these conditions, palmitate failed to alter
      levels of SMs, which are the most abundant sphingolipids, suggesting that they
      are not the primary intermediates accounting for the deleterious palmitate
      effects. Treating cells with a pharmacological inhibitor of SM synthase or using
      CRISPR to knock out the Sms2 gene recapitulated the palmitate effects by inducing
      the accumulation of SM precursors and impairing insulin signaling and
      mitochondrial metabolism. To profile the sphingolipids that accumulate in
      obesity, we performed lipidomics on quadriceps muscles from obese mice with
      impaired glucose tolerance. Like the cultured myotubes, these tissues accumulated
      ceramides but not SMs. Collectively, these data suggest that SM precursors such
      as ceramides, rather than SMs, are likely nutritional antagonists of metabolic
      function in skeletal muscle.

PMID- 27703012
TI  - Role of Glycosyltransferases Modifying Type B Flagellin of Emerging Hypervirulent
      Clostridium difficile Lineages and Their Impact on Motility and Biofilm
      Formation.
AB  - Clostridium difficile is the principal cause of nosocomial infectious diarrhea
      worldwide. The pathogen modifies its flagellin with either a type A or type B O
      linked glycosylation system, which has a contributory role in pathogenesis. We
      study the functional role of glycosyltransferases modifying type B flagellin in
      the 023 and 027 hypervirulent C. difficile lineages by mutagenesis of five
      putative glycosyltransferases and biosynthetic genes. We reveal their roles in
      the biosynthesis of the flagellin glycan chain and demonstrate that flagellar
      post-translational modification affects motility and adhesion-related bacterial
      properties of these strains. We show that the glycosyltransferases 1 and 2 (GT1
      and GT2) are responsible for the sequential addition of a GlcNAc and two
      rhamnoses, respectively, and that GT3 is associated with the incorporation of a
      novel sulfonated peptidyl-amido sugar moiety whose structure is reported in our
      accompanying paper (Bouche, L., Panico, M., Hitchen, P., Binet, D., Sastre, F.,
      Faulds-Pain, A., Valiente, E., Vinogradov, E., Aubry, A., Fulton, K., Twine, S.,
      Logan, S. M., Wren, B. W., Dell, A., and Morris, H. R. (2016) J. Biol. Chem. 291,
      25439-25449). GT2 is also responsible for methylation of the rhamnoses. Whereas
      type B modification is not required for flagellar assembly, some mutations that
      result in truncation or abolition of the glycan reduce bacterial motility and
      promote autoaggregation and biofilm formation. The complete lack of flagellin
      modification also significantly reduces adhesion of C. difficile to Caco-2
      intestinal epithelial cells but does not affect activation of human TLR5. Our
      study advances our understanding of the genes involved in flagellar glycosylation
      and their biological roles in emerging hypervirulent C. difficile strains.

PMID- 27703013
TI  - PvdN Enzyme Catalyzes a Periplasmic Pyoverdine Modification.
AB  - Pyoverdines are high affinity siderophores produced by a broad range of
      pseudomonads to enhance growth under iron deficiency. They are especially
      relevant for pathogenic and mutualistic strains that inhabit iron-limited
      environments. Pyoverdines are generated from non-ribosomally synthesized highly
      modified peptides. They all contain an aromatic chromophore that is formed in the
      periplasm by intramolecular cyclization steps. Although the cytoplasmic peptide
      synthesis and side-chain modifications are well characterized, the periplasmic
      maturation steps are far from understood. Out of five periplasmic enzymes, PvdM,
      PvdN, PvdO, PvdP, and PvdQ, functions have been attributed only to PvdP and PvdQ.
      The other three enzymes are also regarded as essential for siderophore
      biosynthesis. The structure of PvdN has been solved recently, but no function
      could be assigned. Here we present the first in-frame deletion of the PvdN
      encoding gene. Unexpectedly, PvdN turned out to be required for a specific
      modification of pyoverdine, whereas the overall amount of fluorescent pyoverdines
      was not altered by the mutation. The mutant strain grew normally under iron
      limiting conditions. Mass spectrometry identified the PvdN-dependent modification
      as a transformation of the N-terminal glutamic acid to a succinamide. We
      postulate a pathway for this transformation catalyzed by the enzyme PvdN, which
      is most likely functional in the case of all pyoverdines.

PMID- 27703014
TI  - Human ER Oxidoreductin-1alpha (Ero1alpha) Undergoes Dual Regulation through
      Complementary Redox Interactions with Protein-Disulfide Isomerase.
AB  - In the mammalian endoplasmic reticulum, oxidoreductin-1alpha (Ero1alpha)
      generates protein disulfide bonds and transfers them specifically to canonical
      protein-disulfide isomerase (PDI) to sustain oxidative protein folding. This
      oxidative process is coupled to the reduction of O2 to H2O2 on the bound flavin
      adenine dinucleotide cofactor. Because excessive thiol oxidation and H2O2
      generation cause cell death, Ero1alpha activity must be properly regulated. In
      addition to the four catalytic cysteines (Cys94, Cys99, Cys104, and Cys131) that
      are located in the flexible active site region, the Cys208-Cys241 pair located at
      the base of another flexible loop is necessary for Ero1alpha regulation, although
      the mechanistic basis is not fully understood. The present study revealed that
      the Cys208-Cys241 disulfide was reduced by PDI and other PDI family members
      during PDI oxidation. Differential scanning calorimetry and small angle X-ray
      scattering showed that mutation of Cys208 and Cys241 did not grossly affect the
      thermal stability or overall shape of Ero1alpha, suggesting that redox regulation
      of this cysteine pair serves a functional role. Moreover, the flexible loop
      flanked by Cys208 and Cys241 provides a platform for functional interaction with
      PDI, which in turn enhances the oxidative activity of Ero1alpha through reduction
      of the Cys208-Cys241 disulfide. We propose a mechanism of dual Ero1alpha
      regulation by dynamic redox interactions between PDI and the two Ero1alpha
      flexible loops that harbor the regulatory cysteines.

PMID- 27703015
TI  - Sequence-specific and Shape-selective RNA Recognition by the Human RNA 5
      Methylcytosine Methyltransferase NSun6.
AB  - Human NSun6 is an RNA methyltransferase that catalyzes the transfer of the methyl
      group from S-adenosyl-l-methionine (SAM) to C72 of tRNAThr and tRNACys In the
      current study, we used mass spectrometry to demonstrate that human NSun6 indeed
      introduces 5-methylcytosine (m5C) into tRNA, as expected. To further reveal the
      tRNA recognition mechanism of human NSun6, we measured the methylation activity
      of human NSun6 and its kinetic parameters for different tRNA substrates and their
      mutants. We showed that human NSun6 requires a well folded, full-length tRNA as
      its substrate. In the acceptor region, the CCA terminus, the target site C72, the
      discriminator base U73, and the second and third base pairs (2:71 and 3:70) of
      the acceptor stem are all important RNA recognition elements for human NSun6. In
      addition, two specific base pairs (11:24 and 12:23) in the D-stem of the tRNA
      substrate are involved in interacting with human NSun6. Together, our findings
      suggest that human NSun6 relies on a delicate network for RNA recognition, which
      involves both the primary sequence and tertiary structure of tRNA substrates.

PMID- 27703018
TI  - Experimental induction of mycotic plaques in the guttural pouches of horses.
AB  - Guttural pouch mycosis (GPM) is a rare but potentially life-threatening condition
      in horses. GPM is caused by a fungal invasion into the mucosal lining of the
      guttural pouches and, frequently, the associated neurovascular structures.
      Although several species of fungi have been associated with this disease,
      Aspergillus spp. appear to be the most common isolated from the guttural pouches.
      However, it remains unclear which are the predisposing factors leading to the
      development of the infection. The objectives of the present study were to
      experimentally reproduce an infection by Aspergillus fumigatus and to follow the
      natural evolution of the mycosis. Eight guttural pouches from four horses were
      experimentally infected by endoscopy-guided intrapouch inoculation of A.
      fumigatus culture. Horses were monitored for clinical signs and development of
      fungal plaques through endoscopic examination. Mycotic lesions were observed in
      all the horses and a spontaneous regression was observed within 15-28 days. No
      development of clinical signs was noticed. In conclusion, we were able to induce
      the development of mycotic lesions and to observe a natural regression of these
      lesions without clinical signs.

PMID- 27703016
TI  - Posaconazole plasma concentrations in pediatric patients receiving antifungal
      prophylaxis during neutropenia.
AB  - Invasive fungal infections are one of the major complications in pediatric
      patients during prolonged neutropenia after chemotherapy. Evaluation of the
      efficacy and safety of the triazole posaconazole in these patients is missing.
      This multicenter survey analyzed trough concentrations of 33 pediatric patients
      with a median age of 8 years during 108 neutropenic episodes who received
      prophylactic posaconazole oral suspension. A total of 172 posaconazole trough
      levels were determined to median 438 ng/ml (range 111-2011 ng/ml; mean 468 +/-
      244 ng/ml). Age and gender had no influence on posaconazole plasma levels.
      Posaconazole was not discontinued due to adverse events in any of the patients.
      Only hepatic parameters significantly increased beyond the upper normal limit to
      median values of ALT of 87 U/l (P < .0001), and AST of 67 U/l (P < .0001). One
      patient with a median posaconazole trough concentration of 306 ng/ml experienced
      an invasive fungal infection. In conclusion, posaconazole was effective, safe and
      feasible in 33 pediatric patients with neutropenia >=5 days after chemotherapy.
      Median posaconazole plasma concentrations were approximately 1.6-fold lower than
      the recommended plasma level of 700 ng/ml. Larger patient cohorts are needed to
      evaluate these findings.

PMID- 27703019
TI  - Chemical and physical strategies in onychomycosis topical treatment: A review.
AB  - Onychomycosis is a fungal infection of the fingernails or toenails caused by
      dermatophytes, nondermatophytes, moulds, and yeasts. This condition affects
      around 10-30% people worldwide, negatively influencing patients' quality of life,
      with severe outcomes in some cases. Since the nail unit acts as a barrier to
      exogenous substances, its physiological features hampers drug penetration,
      turning the onychomycosis treatment a challenge. Currently, there are several
      oral and topical therapies available; nevertheless, cure rates are still low and
      relapse rates achieves 10-53%. Also, serious side effects may be developed due to
      long-term treatment. In light of these facts, researchers have focused on
      improving topical treatments, either by modifying the vehicle or by using some
      physical technique to improve drug delivery trough the nail plate, hence
      increasing therapy effectiveness. Therefore, the aim of this paper is to explain
      these novel alternative approaches. First, the challenges for drug ungual
      penetration are presented. Then, the chemical and physical strategies developed
      for overcoming the barriers for drug penetration are discussed. We hope that the
      information gathered may be useful for the development of safer and more
      effective treatments for onychomycosis.

PMID- 27703017
TI  - Hospitalized burden and outcomes of coccidioidomycosis: A nationwide analysis,
      2005-2012.
AB  - The incidence of coccidioidomycosis (CM) infection has increased over the last 20
      years. We investigated recent trends of CM-associated hospitalization in the
      United States. patients with CM-associated hospitalization were identified from
      the Nationwide Inpatient Sample, 2005-2012. The outcomes of interest were the
      trend of annual hospitalization, in-hospital mortality, and independent risk
      factors for mortality. A total of 30,870 hospitalizations with CM (29,584 of
      adults; 1,286 of children) were identified. Over the 8-year study period, the
      number of hospitalizations for CM fluctuated but increased overall with
      successively higher peaks in 2009 and 2011. The annual median length of stay
      (LOS) shortened from 6 to 7 days in 2005-2010 to 4 days in 2011 and 5 days in
      2012. The inflation-adjusted hospital charges were highest in 2006 then trended
      down by 21% in 2012. The in-hospital mortality declined from the highest level in
      2005 (5.2%) to a low in 2010 (1.1%), then increased modestly in 2011 (1.9%) and
      2012 (1.5%). Hospitalizations were identified in 46 states, with nearly half in
      Arizona (49.1%), followed by California (36.8%), Texas (3.3%), and Nevada (1.6%).
      Logistic regression analysis in adults revealed that in-hospital mortality was
      associated with age groups 61-70 years and >70 years (OR = 3.3 and 3.5,
      respectively. Ref: 18-30 years) and Charlson Index >=1 (OR = 2.0-8.3). In
      children, males had lower risk for mortality than females (OR = 0.2). This study
      shows that CM-associated hospitalizations occur widely throughout the United
      States with an increasing admission trend; however, patient outcomes have
      improved and the cost of hospitalization has decreased.

PMID- 27703020
TI  - Gut yeast communities in Larus michahellis from various breeding colonies.
AB  - Yellow-legged gulls have been reported to carry antibiotic-resistant
      Enterobacteriaceae; however, the gut mycobiota of these birds has not yet been
      described. In this study, we analyzed the gut yeast communities in five yellow
      legged gull breeding colonies along the Mediterranean littoral in southern
      France. Gull fecal samples were inoculated onto four types of culture media,
      including one supplemented with itraconazole. Yeast species richness, abundance,
      and diversity were estimated, and factorial analysis was used to highlight
      correspondences between breeding colonies. Yeast grew in 113 of 177 cultures, and
      17 distinct yeast species were identified. The most frequent species were Candida
      krusei (53.5%), Galactomyces geotrichum (44.1%), C. glabrata (40.9%), C. albicans
      (20.5%), and Saccharomyces cerevisiae (18.1%). Gut yeast community structure in
      the gulls at both Pierre-Blanche Lagoon (PB) and Frioul Archipelago (F) were
      characterized by greater species richness and diversity than in those at the two
      cities of La Grande-Motte (GM) and Palavas-les-Flots (PF) as well as Riou
      Archipelago (R). Gulls in these latter three sites probably share a similar type
      of anthropogenic diet. Notably, the proportion of anthropic yeast species,
      including C. albicans and C. glabrata, in the gull mycobiota increased with gull
      colony synanthropy. Antifungal resistance was found in each of the five most
      frequent yeast species. We found that the gut yeast communities of these yellow
      legged gulls include antifungal-resistant human pathogens. Further studies should
      assess the public health impact of these common synanthropic seabirds, which
      represent a reservoir and disseminator of drug-resistant human pathogenic yeast
      into the environment.

PMID- 27703021
TI  - Aspergillus antibody detection: diagnostic strategy and technical considerations
      from the Societe Francaise de Mycologie Medicale (French Society for Medical
      Mycology) expert committee.
AB  - Until now, there has been no consensus on the best method for the detection of
      anti-Aspergillus antibodies, a key diagnostic tool for chronic aspergilloses. To
      better appreciate the usage of and confidence in these techniques, the Societe
      Francaise de Mycologie Medicale (French Society for Medical Mycology; SFMM)
      performed a two-step survey of French experts. First, we administered an initial
      survey to French labs performing Aspergillus serology to depict usage of the
      different techniques available for Aspergillus serology. Second, an opinion poll
      was conducted of 40 experts via an online questionnaire. Each item was rated from
      1 to 9 according to the level of agreement. The initial survey revealed that
      enzyme-linked immunosorbent assay (ELISA) (81%) and immunoelectrophoresis (IEP)
      (67%) were the most commonly used techniques for screening and confirmation,
      respectively. The distinction between screening and confirmation techniques was
      confirmed by the experts (median = 7) with a 44.2% variation coefficient. Only
      ELISA for screening and IEP and Western blot (WB) for confirmation were clearly
      considered valuable methods (median >=8 with variation coefficients less than
      30%). The use of a confirmation technique was recommended in the case of a
      positive result in a compatible clinical context (cystic fibrosis, for example)
      or during the patient's follow-up. In the case of discordant results between the
      screening and confirmation techniques, the experts recommended greater confidence
      in the results obtained with the confirmation technique. All experts emphasized
      the need to standardize Aspergillus serology techniques and to better define the
      place of each of them in the diagnosis of aspergillosis.

PMID- 27703022
TI  - Epidemiological features of invasive mold infections among solid organ transplant
      recipients: PATH Alliance(r) registry analysis.
AB  - Epidemiological characteristics of 333 proven and probable invasive mould
      infections (IMIs) among solid organ transplant recipients (SOTRs) identified
      between 2004 and 2008 from the Prospective Antifungal Therapy Alliance (PATH)
      registry are presented. Liver transplant recipients (LTRs) had the lowest median
      time to IMIs (109 days; interquartile range [IQR] 24-611 days), the highest rate
      of disseminated disease (n/N = 18/33; 55%), and highest mortality (n/N = 21/33;
      64%). Lung transplant recipients had highest median time to IMIs (486 days; IQR
      117-1358 days) and lowest mortality (n/N = 31/184; 17%). Complete or partial
      response at week 12 in patients with invasive aspergillosis (IA) was 67% (n/N =
      189/281), and 41% (n/N = 9/22) in mucormycosis patients. In the composite outcome
      of death or no response to therapy, LTRs had the worst outcome. Higher suspicion
      of mold infection and institution of appropriate antifungal prophylactic
      strategies are warranted, especially in high risk LTRs.

PMID- 27703023
TI  - Dosing and therapeutic drug monitoring of voriconazole in bottlenose dolphins
      (Tursiops truncatus).
AB  - Bottlenose dolphins (Tursiops truncatus) can suffer from fungal infections, which
      can be treated with voriconazole. In common practice, the voriconazole doses are
      extrapolated from human doses by adjusting for body weight only, because no dose
      regimen is available yet. Therefore, the aim of this study was to define a dose
      regimen for voriconazole in bottlenose dolphins. Dolphins treated with
      voriconazole between November 2005 and September 2015 at the Dolfinarium
      Harderwijk, the Netherlands, and TDM was performed were included. Voriconazole
      plasma concentrations were analyzed with a HPLC-UV method. A population
      pharmacokinetic model was developed using Mw/Pharm in which the elimination rate
      constant (ke) and apparent total distribution volume (Vd) was calculated. The
      loading dose was calculated using the central Vd (Vdc). The maintenance dose was
      simulated in Mw/Pharm using ke and total Vd.Eleven dolphins were included. Ke was
      estimated to be 0.0026 +/- 0.0007 hour-1 (mean +/- SD), Vd 5.3 +/- 3.2 l/kg (mean
      +/- SD), and Vdc ranged between 1.8 and 2.8 l/kg (mean 2.2 l/kg). In order to
      obtain a median top plasma concentration of 5 mg/l, the loading dose was
      calculated to be 10 mg/kg (range 9.0-14.2 mg/kg) divided in three administrations
      (3.3 mg/kg every 24 hours). The maintenance dose was calculated to be 4 mg/kg
      once a week (range 1.7-6.0 mg/kg); 17% of the dolphins did not reach the
      therapeutic window of 1-5 mg/l without TDM. A TDM-guided dosing algorithm was
      developed in order to obtain therapeutic plasma concentrations in this
      population.

PMID- 27703024
TI  - Plasma Triglycerides and HDL-C Levels Predict the Development of Diabetic Kidney
      Disease in Subjects With Type 2 Diabetes: The AMD Annals Initiative.
AB  - OBJECTIVE: Despite the achievement of blood glucose, blood pressure, and LDL
      cholesterol (LDL-C) targets, the risk for diabetic kidney disease (DKD) remains
      high among patients with type 2 diabetes. This observational retrospective study
      investigated whether diabetic dyslipidemia-that is, high triglyceride (TG) and/or
      low HDL cholesterol (HDL-C) levels-contributes to this high residual risk for
      DKD. RESEARCH DESIGN AND METHODS: Among a total of 47,177 patients attending
      Italian diabetes centers, 15,362 patients with a baseline estimated glomerular
      filtration rate (eGFR) >=60 mL/min/1.73 m2, normoalbuminuria, and LDL-C <=130
      mg/dL completing a 4-year follow-up were analyzed. The primary outcome was the
      incidence of DKD, defined as either low eGFR (<60 mL/min/1.73 m2) or an eGFR
      reduction >30% and/or albuminuria. RESULTS: Overall, 12.8% developed low eGFR,
      7.6% an eGFR reduction >30%, 23.2% albuminuria, and 4% albuminuria and either
      eGFR <60 mL/min/1.73 m2 or an eGFR reduction >30%. TG >=150 mg/dL increased the
      risk of low eGFR by 26%, of an eGFR reduction >30% by 29%, of albuminuria by 19%,
      and of developing one abnormality by 35%. HDL-C <40 mg/dL in men and <50 mg/dL in
      women were associated with a 27% higher risk of low eGFR and a 28% risk of an
      eGFR reduction >30%, with a 24% higher risk of developing albuminuria and a 44%
      risk of developing one abnormality. These associations remained significant when
      TG and HDL-C concentrations were examined as continuous variables and were only
      attenuated by multivariate adjustment for numerous confounders. CONCLUSIONS: In a
      large population of outpatients with diabetes, low HDL-C and high TG levels were
      independent risk factors for the development of DKD over 4 years.

PMID- 27703025
TI  - An Unbiased Lipidomics Approach Identifies Early Second Trimester Lipids
      Predictive of Maternal Glycemic Traits and Gestational Diabetes Mellitus.
AB  - OBJECTIVE: To investigate the relationship between early second trimester serum
      lipidomic variation and maternal glycemic traits at 28 weeks and to identify
      predictive lipid biomarkers for gestational diabetes mellitus (GDM). RESEARCH
      DESIGN AND METHODS: Prospective study of 817 pregnant women (discovery cohort, n
      = 200; validation cohort, n = 617) who provided an early second trimester serum
      sample and underwent an oral glucose tolerance test (OGTT) at 28 weeks. In the
      discovery cohort, lipids were measured using direct infusion mass spectrometry
      and correlated with OGTT results. Variable importance in projection (VIP) scores
      were used to identify candidate lipid biomarkers. Candidate biomarkers were
      measured in the validation cohort using liquid chromatography-mass spectrometry
      and tested for associations with OGTT results and GDM status. RESULTS: Early
      second trimester lipidomic variation was associated with 1-h postload glucose
      levels but not with fasting plasma glucose levels. Of the 13 lipid species
      identified by VIP scores, 10 had nominally significant associations with postload
      glucose levels. In the validation cohort, 5 of these 10 lipids had significant
      associations with postload glucose levels that were independent of maternal age
      and BMI, i.e., TG(51.1), TG(48:1), PC(32:1), PCae(40:3), and PCae(40:4). All
      except the last were also associated with maternal GDM status. Together, these
      four lipid biomarkers had moderate ability to predict GDM (area under curve [AUC]
      = 0.71 +/- 0.04, P = 4.85 * 10-7) and improved the prediction of GDM by age and
      BMI alone from AUC 0.69 to AUC 0.74. CONCLUSIONS: Specific early second trimester
      lipid biomarkers can predict maternal GDM status independent of maternal age and
      BMI, potentially enhancing risk factor-based screening.

PMID- 27703027
TI  - No Summer Vacation From Diabetes: Glycemic Control in Pediatric Participants in
      the T1D Exchange Registry Based on Time of Year.

PMID- 27703026
TI  - Exposure to Gestational Diabetes Mellitus: Impact on the Development of Early
      Onset Type 2 Diabetes in Canadian First Nations and Non-First Nations Offspring.
AB  - OBJECTIVE: Type 2 diabetes is increasing in children worldwide, with Canadian
      First Nations (FN) children disproportionally affected. The prevalence of
      gestational diabetes mellitus (GDM) also is increasing. The objective of this
      study was to evaluate the impact of GDM exposure in utero and FN status on the
      subsequent risk of type 2 diabetes in offspring in the first 30 years of life.
      RESEARCH DESIGN AND METHODS: In this population-based historical prospective
      cohort study, we used administrative databases linked to a clinical database to
      explore the independent association and interaction between GDM and FN status on
      the subsequent development of type 2 diabetes in offspring. RESULTS: Among
      321,008 births with a median follow-up of 15.1 years, both maternal GDM and FN
      status were independently associated with subsequent risk of type 2 diabetes in
      offspring in the first 30 years of life (hazard ratio 3.03 [95% CI 2.44-3.76; P <
      0.0001] vs. 4.86 [95% CI 4.08-5.79; P < 0.0001], respectively). No interaction
      between GDM and FN status on type 2 diabetes risk was observed. FN status had a
      stronger impact on the development of type 2 diabetes in offspring than GDM.
      CONCLUSIONS: GDM is an important modifiable risk factor for type 2 diabetes, and
      its prevention may reduce the prevalence of subsequent type 2 diabetes in
      offspring. This study adds unique and rigorous evidence to the global public
      health debate about the impact of GDM on the long-term health of offspring.

PMID- 27703029
TI  - New twists in the AXL(e) of tumor progression.
AB  - Patients with a mesenchymal subtype of ovarian cancer face a poor prognosis with
      limited treatment options to halt metastatic progression. In this issue of
      Science Signaling, Antony et al found that the kinase AXL drives the mesenchymal
      gene signature and motility of ovarian tumor cells. AXL inhibitors may thus slow
      tumor progression in this subset of patients.

PMID- 27703028
TI  - APOE Genotypes Associate With Cognitive Performance but Not Cerebral Structure:
      Diabetes Heart Study MIND.
AB  - OBJECTIVE: Dementia is a debilitating illness with a disproportionate burden in
      patients with type 2 diabetes (T2D). Among the contributors, genetic variation at
      the apolipoprotein E locus (APOE) is posited to convey a strong effect. This
      study compared and contrasted the association of APOE with cognitive performance
      and cerebral structure in the setting of T2D. RESEARCH DESIGN AND METHODS:
      European Americans from the Diabetes Heart Study (DHS) MIND (n = 754) and African
      Americans from the African American (AA)-DHS MIND (n = 517) were examined. The
      cognitive battery assessed executive function, memory, and global cognition, and
      brain MRI was performed. RESULTS: In European Americans and African Americans,
      the APOE E4 risk haplotype group was associated with poorer performance on the
      modified Mini-Mental Status Examination (P < 0.017), a measure of global
      cognition. In contrast to the literature, the APOE E2 haplotype group, which was
      overrepresented in these participants with T2D, was associated with poorer Rey
      Auditory Verbal Learning Test performance (P < 0.032). Nominal associations
      between APOE haplotype groups and MRI-determined cerebral structure were
      observed. CONCLUSIONS: Compared with APOE E3 carriers, E2 and E4 carriers
      performed worse in the cognitive domains of memory and global cognition.
      Identification of genetic contributors remains critical to understanding new
      pathways to prevent and treat dementia in the setting of T2D.

PMID- 27703031
TI  - Quantitative phosphoproteomic analysis identifies the critical role of JNK1 in
      neuroinflammation induced by Japanese encephalitis virus.
AB  - Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis
      worldwide. The pathogenesis of JEV is linked to a robust inflammatory response in
      the central nervous system (CNS). Glial cells are the resident immune cells in
      the CNS and represent critical effectors of CNS inflammation. To obtain a global
      overview of signaling events in glial cells during JEV infection, we conducted
      phosphoproteomics profiling of a JEV-infected glial cell line. We identified 1816
      phosphopeptides, corresponding to 1264 proteins, that exhibited a change in
      phosphorylation status upon JEV infection. Bioinformatics analysis revealed that
      these proteins were predominantly related to transcription regulation, signal
      transduction, the cell cycle, and the cytoskeleton. Kinase substrate motif
      revealed that substrates for c-Jun N-terminal kinase 1 (JNK1) were the most
      overrepresented, along with evidence of increased AKT1 and protein kinase A (PKA)
      signaling. Pharmacological inhibition of JNK, AKT, or PKA reduced the
      inflammatory response of cultured glial cells infected with JEV, as did knockdown
      of JNK1 or its target JUN. JEV genomic RNA was sufficient to activate JNK1
      signaling in cultured glial cells. Of potential clinical relevance, we showed
      that inhibition of JNK signaling significantly attenuated the production of
      inflammatory cytokines in the brain and reduced lethality in JEV-infected mice,
      thereby suggesting that JNK signaling is a potential therapeutic target for the
      management of Japanese encephalitis.

PMID- 27703030
TI  - The GAS6-AXL signaling network is a mesenchymal (Mes) molecular subtype-specific
      therapeutic target for ovarian cancer.
AB  - Ovarian cancer is a complex disease with heterogeneity among the gene expression
      molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal
      ("Mes") subtype have a poorer prognosis than patients with tumors of an
      epithelial ("Epi") subtype. We evaluated GEMS of ovarian cancer patients for
      molecular signaling profiles and assessed how the differences in these profiles
      could be leveraged to improve patient clinical outcome. Kinome enrichment
      analysis identified AXL as a particularly abundant kinase in Mes-subtype tumor
      tissue and cell lines. In Mes cells, upon activation by its ligand GAS6, AXL
      coclustered with and transactivated the receptor tyrosine kinases (RTKs) cMET,
      EGFR, and HER2, producing sustained extracellular signal-regulated kinase (ERK)
      activation. In Epi-A cells, AXL was less abundant and induced a transient
      activation of ERK without evidence of RTK transactivation. AXL-RTK crosstalk also
      stimulated sustained activation of the transcription factor FRA1, which
      correlated with the induction of the epithelial-mesenchymal transition (EMT)
      associated transcription factor SLUG and stimulation of motility exclusively in
      Mes-subtype cells. The AXL inhibitor R428 attenuated RTK and ERK activation and
      reduced cell motility in Mes cells in culture and reduced tumor growth in a chick
      chorioallantoic membrane model. A higher concentration of R428 was needed to
      inhibit ERK activation and cell motility in Epi-A cells. Silencing AXL in Mes
      subtype cells reversed the mesenchymal phenotype in culture and abolished tumor
      formation in an orthotopic xenograft mouse model. Thus, AXL-targeted therapy may
      improve clinical outcome for patients with Mes-subtype ovarian cancer.

PMID- 27703032
TI  - Superresolution imaging of the cytoplasmic phosphatase PTPN22 links integrin
      mediated T cell adhesion with autoimmunity.
AB  - Integrins are heterodimeric transmembrane proteins that play a fundamental role
      in the migration of leukocytes to sites of infection or injury. We found that
      protein tyrosine phosphatase nonreceptor type 22 (PTPN22) inhibits signaling by
      the integrin lymphocyte function-associated antigen-1 (LFA-1) in effector T
      cells. PTPN22 colocalized with its substrates at the leading edge of cells
      migrating on surfaces coated with the LFA-1 ligand intercellular adhesion
      molecule-1 (ICAM-1). Knockout or knockdown of PTPN22 or expression of the
      autoimmune disease-associated PTPN22-R620W variant resulted in the enhanced
      phosphorylation of signaling molecules downstream of integrins. Superresolution
      imaging revealed that PTPN22-R620 (wild-type PTPN22) was present as large
      clusters in unstimulated T cells and that these disaggregated upon stimulation of
      LFA-1, enabling increased association of PTPN22 with its binding partners at the
      leading edge. The failure of PTPN22-R620W molecules to be retained at the leading
      edge led to increased LFA-1 clustering and integrin-mediated cell adhesion. Our
      data define a previously uncharacterized mechanism for fine-tuning integrin
      signaling in T cells, as well as a paradigm of autoimmunity in humans in which
      disease susceptibility is underpinned by inherited phosphatase mutations that
      perturb integrin function.

PMID- 27703033
TI  - Video-Only Cardiopulmonary Resuscitation Education for High-Risk Families Before
      Hospital Discharge: A Multicenter Pragmatic Trial.
AB  - BACKGROUND: Cardiopulmonary resuscitation (CPR) training rates in the United
      States are low, highlighting the need to develop CPR educational approaches that
      are simpler, with broader dissemination potential. The minimum training required
      to ensure long-term skill retention remains poorly characterized. We compared CPR
      skill retention among laypersons randomized to training with video-only (VO; no
      manikin) with those trained with a video self-instruction kit (VSI; with
      manikin). We hypothesized that VO training would be noninferior to the VSI
      approach with respect to chest compression (CC) rate. METHODS AND RESULTS: We
      performed a prospective, cluster randomized trial of CPR education for family
      members of patients with high-risk cardiac conditions on hospital cardiac units,
      using a multicenter pragmatic design. Eight hospitals were randomized to offer
      either VO or VSI training before discharge using volunteer trainers. CPR skills
      were assessed 6 months post training. Mean CC rate among those trained with VO
      compared with those trained with VSI was assessed with a noninferiority margin
      set at 8 CC per min; as a secondary outcome, mean differences in CC depth were
      assessed. From February 2012 to May 2015, 1464 subjects were enrolled and 522
      subjects completed a skills assessment. The mean CC rates were 87.7 (VO) CC per
      min and 89.3 (VSI) CC per min; we concluded noninferiority for VO based on a mean
      difference of -1.6 (90% confidence interval, -5.2 to 2.1). The mean CC depth was
      40.2 mm (VO) and 45.8 mm (VSI) with a mean difference of -5.6 (95% confidence
      interval, -7.6 to -3.7). Results were similar after multivariate regression
      adjustment. CONCLUSIONS: In this large, prospective trial of CPR skill retention,
      VO training yielded a noninferior difference in CC rate compared with VSI
      training. CC depth was greater in the VSI group. These findings suggest a
      potential trade-off in efforts for broad dissemination of basic CPR skills; VO
      training might allow for greater scalability and dissemination, but with a
      potential reduction in CC depth. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT01514656.

PMID- 27703034
TI  - Clinical Impact of Subsequent Depression in Patients With a New Diagnosis of
      Stable Angina: A Population-Based Study.
AB  - BACKGROUND: Depression is prevalent among patients with myocardial infarction and
      is associated with a worse prognosis. However, little is known about its
      importance in patients with chronic stable angina. We conducted a retrospective
      population-based cohort study to determine the occurrence and predictors of
      developing depression in patients with a new diagnosis of chronic stable angina.
      In addition, we sought to understand its impact on subsequent clinical outcomes.
      METHODS AND RESULTS: Our cohort included patients in Ontario, Canada, with stable
      angina based on obstructive coronary artery disease found on angiogram.
      Depression was ascertained by physician billing codes and hospital admissions
      diagnostic codes. We first developed multivariable Cox proportional hazards
      models to determine predictors of developing depression. Clinical outcomes of
      interest included all-cause mortality, admission for myocardial infarction, and
      subsequent revascularization. Using hierarchical multivariable Cox proportional
      hazards models with occurrence of depression as a time-varying variable to
      control for potential immortal time bias, we evaluated the impact of depression
      on clinical outcomes. Our cohort consisted of 22 917 patients. The occurrence of
      depression after diagnosis of stable chronic angina was 18.8% over a mean follow
      up of 1084 days. Predictors of depression included remote history of depression,
      female sex, and more symptomatic angina based on Canadian Cardiovascular Society
      class. Patients who developed depression had a higher risk of death (hazard ratio
      1.83, 95% confidence interval 1.62-2.07) and admission for myocardial infarction
      (hazard ratio 1.36, 95% confidence interval 1.10-1.67) compared with nondepressed
      patients. CONCLUSIONS: Depression is common in patients with chronic stable
      angina and is associated with increased morbidity and mortality.

PMID- 27703036
TI  - Does Bacterial Vaginosis Result From Fecal Transplantation?

PMID- 27703035
TI  - CD4+ T Cells Coexpressing CD134 (OX40) Harbor Significantly Increased Levels of
      Human Herpesvirus 6B DNA Following Umbilical Cord Blood Transplantation.
AB  - Human herpesvirus 6B (HHV-6B) commonly reactivates after umbilical cord blood
      transplantation (UCBT) and is associated with delayed engraftment, fever, rash,
      and central nervous system dysfunction. Recently, CD134 (OX40) has been
      implicated as a potential viral entry receptor. We evaluated CD4+CD134+/neg-lo
      and CD8+CD134+/neg-lo cells at day 28 after UCBT in 20 subjects with previously
      documented HHV-6 reactivation and persistent viremia. Analysis of CD4+CD134+
      cells as compared to CD4+CD134neg-lo cells showed 0.308 versus 0.129 copies of
      HHV-6B/cell (P = .0002). CD8+CD134+/neg-lo cells contained little to no HHV-6B
      copies. Following UCBT, CD4+CD134+ cells harbor significantly increased levels of
      HHV-6B, suggesting that CD134 (OX40) may facilitate viral entry.

PMID- 27703037
TI  - Identification of Coxiella burnetii CD8+ T-Cell Epitopes and Delivery by
      Attenuated Listeria monocytogenes as a Vaccine Vector in a C57BL/6 Mouse Model.
AB  - Coxiella burnetii is a gram-negative bacterium that causes acute and chronic Q
      fever. Because of the severe adverse effect of whole-cell vaccination,
      identification of immunodominant antigens of C. burnetii has become a major focus
      of Q fever vaccine development. We hypothesized that secreted C. burnetii type IV
      secretion system (T4SS) effectors may represent a major class of CD8+ T-cell
      antigens, owing to their cytosolic localization. Twenty-nine peptides were
      identified that elicited robust CD8+ T-cell interferon gamma (IFN-gamma) recall
      responses from mice infected with C. burnetii. Interestingly, 22 of 29 epitopes
      were derived from 17 T4SS-related proteins, none of which were identified as
      immunodominant antigens by using previous antibody-guided approaches. These
      epitopes were expressed in an attenuated Listeria monocytogenes vaccine strain.
      Immunization with recombinant L. monocytogenes vaccines induced a robust CD8+ T
      cell response and conferred measurable protection against C. burnetii infection
      in mice. These data suggested that T4SS effectors represent an important class of
      C. burnetii antigens that can induce CD8+ T-cell responses. We also showed that
      attenuated L. monocytogenes vaccine vectors are an efficient antigen-delivery
      platform that can be used to induce robust protective CD8+ T-cell immune
      responses against C. burnetii infection.

PMID- 27703038
TI  - Induction of an Immune-Protective T-Cell Repertoire With Diverse Genetic Coverage
      by a Novel Viral-Vectored Tuberculosis Vaccine in Humans.
AB  - BACKGROUND:  Whether a candidate tuberculosis vaccine induces clinically relevant
      protective T-cell repertoires in humans will not be known until the completion of
      costly efficacy clinical trials. METHODS:  We have developed an integrated
      immunologic approach to investigate the clinical relevance of T cells induced by
      a novel tuberculosis vaccine in a phase 1 trial. This approach consists of
      screening for likely dominant T-cell epitopes, establishing antigen-specific
      memory T-cell lines for identifying CD8+ and CD4+ T-cell epitopes, determining
      the ability of vaccine-induced T cells to inhibit mycobacterial growth in
      infected cells, and examining the genetic diversity of HLA recognition and the
      clinical relevance of identified T-cell epitopes. RESULTS:  A single-dose
      immunization in BCG-primed adults with an adenovirus-based tuberculosis vaccine
      elicits a repertoire of memory T cells capable of recognizing multiple Ag85A
      epitopes. These T cells are polyfunctional and cytotoxic and can inhibit
      mycobacterial growth in infected target cells. Some identified T-cell epitopes
      are promiscuous and recognizable by the common HLA alleles. These epitopes are
      clinically relevant to the epitopes identified in people with latent
      Mycobacterium tuberculosis infection and treated patients with tuberculosis.
      CONCLUSIONS:  These data support further clinical development of this candidate
      vaccine. Our approach helps fill the gap in clinical tuberculosis vaccine
      development.

PMID- 27703039
TI  - Inflammatory Function of CX3CR1+ CD8+ T Cells in Treated HIV Infection Is
      Modulated by Platelet Interactions.
AB  - Increases in inflammation, coagulation, and CD8+ T-cell numbers are associated
      with an elevated cardiovascular disease (CVD) risk in human immunodeficiency
      virus (HIV)-infected antiretroviral therapy (ART) recipients. Circulating memory
      CD8+ T cells that express the vascular endothelium-homing receptor CX3CR1
      (fractalkine receptor) are enriched in HIV-infected ART recipients. Thrombin
      activated receptor (PAR-1) expression is increased in HIV-infected ART recipients
      and is particularly elevated on CX3CR1+ CD8+ T cells, suggesting that these cells
      could interact with coagulation elements. Indeed, thrombin directly enhanced T
      cell receptor-mediated interferon gamma production by purified CD8+ T cells but
      was attenuated by thrombin-induced release of transforming growth factor beta by
      platelets. We have therefore identified a population of circulating memory CD8+ T
      cells in HIV infection that may home to endothelium, can be activated by clot
      forming elements, and are susceptible to platelet-mediated regulation. Complex
      interactions between inflammatory elements and coagulation at endothelial
      surfaces may play an important role in CVD risk in HIV-infected ART recipients.

PMID- 27703041
TI  - Comparison of the anti-duck hepatitis A virus activities of phosphorylated and
      sulfated Astragalus polysaccharides.
AB  - Duck hepatitis A virus (DHAV) (Picornaviridae) causes an infectious disease in
      ducks which results in severe losses in duck industry. However, the proper
      antiviral supportive drugs for this disease have not been discovered.
      Polysaccharide is the main ingredient of Astragalus that has been demonstrated to
      directly and indirectly inhibit RNA of viruses replication. In this study, the
      antiviral activities of Astragalus polysaccharide (APS) and its derivatives
      against DHAV were evaluated and compared. APS was modified via the sodium
      trimetaphosphate and sodium tripolyphosphate (STMP-STPP) method and
      chlorosulfonic acid-pyridine method to obtain its phosphate (pAPS) and sulfate
      (sAPS), respectively. The infrared structures of APS, pAPS, and sAPS were
      analyzed with the potassium bromide disc method. Additionally, the antiviral
      activities were evaluated with the MTT ((4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2
      H-tetrazolium bromide) method in vitro and the artificial inoculation method in
      vivo. The clinical therapy effects were evaluated by mortality rate, liver
      function-related biochemical indicators, and visual changes in pathological
      anatomy. The anti-DHAV proliferation effects of APS, pAPS, and sAPS on the viral
      multiplication process in cell and blood were observed with the reverse
      transcription-polymerase chain reaction method. The results revealed that pAPS
      inhibited DHAV proliferation more efficiently in the entire process of viral
      multiplication than APS and sAPS. Moreover, only pAPS significantly improved the
      survival rate to 33.5% and reduced the DHAV particle titer in the blood as well
      as liver lesions in clinical trials. The results indicated that pAPS exhibited
      greater anti-DHAV activity than APS and sAPS both in vitro and in vivo.

PMID- 27703040
TI  - The Salivary Protein Repertoire of the Polyphagous Spider Mite Tetranychus
      urticae: A Quest for Effectors.
AB  - The two-spotted spider mite Tetranychus urticae is an extremely polyphagous crop
      pest. Alongside an unparalleled detoxification potential for plant secondary
      metabolites, it has recently been shown that spider mites can attenuate or even
      suppress plant defenses. Salivary constituents, notably effectors, have been
      proposed to play an important role in manipulating plant defenses and might
      determine the outcome of plant-mite interactions. Here, the proteomic composition
      of saliva from T. urticae lines adapted to various host plants-bean, maize, soy,
      and tomato-was analyzed using a custom-developed feeding assay coupled with nano
      LC tandem mass spectrometry. About 90 putative T. urticae salivary proteins were
      identified. Many are of unknown function, and in numerous cases belonging to
      multimembered gene families. RNAseq expression analysis revealed that many genes
      coding for these salivary proteins were highly expressed in the proterosoma, the
      mite body region that includes the salivary glands. A subset of genes encoding
      putative salivary proteins was selected for whole-mount in situ hybridization,
      and were found to be expressed in the anterior and dorsal podocephalic glands.
      Strikingly, host plant dependent expression was evident for putative salivary
      proteins, and was further studied in detail by micro-array based genome-wide
      expression profiling. This meta-analysis revealed for the first time the salivary
      protein repertoire of a phytophagous chelicerate. The availability of this
      salivary proteome will assist in unraveling the molecular interface between
      phytophagous mites and their host plants, and may ultimately facilitate the
      development of mite-resistant crops. Furthermore, the technique used in this
      study is a time- and resource-efficient method to examine the salivary protein
      composition of other small arthropods for which saliva or salivary glands cannot
      be isolated easily.

PMID- 27703044
TI  - Older men with severe disc degeneration have more incident vertebral fractures
      the prospective MINOS cohort study.
AB  - OBJECTIVE: Data on the relationship between disc degeneration (DD) and fragility
      fractures in men are limited. The aim of this study was to prospectively analyse
      the risk of vertebral and non-vertebral fractures in men with thoracolumbar DD
      according to the severity of its radiological signs: disc space narrowing (DSN),
      osteophytes and endplate sclerosis. METHODS: Men >50 years of age (n = 765) had
      lateral spine radiographs and DXA and were monitored prospectively. We analysed
      the risk of incident vertebral (7.5 years) and non-vertebral fractures (10 years)
      in men according to the severity of DD. RESULTS: After adjustment for age and
      weight, BMD increased with increasing total DSN score, endplate sclerosis and
      osteophytosis. Over 7.5 years, 28 incident vertebral fractures occurred in 27
      men. After adjustment for age, BMI, spine BMD, prior fractures and abdominal
      aortic calcifications, the vertebral fracture risk was 3-fold higher in the upper
      DSN quartile vs men without DSN. After adjustment for the same confounders,
      vertebral fracture risk was also nearly 3-fold higher in the upper DSN quartile
      vs the three lower quartiles combined. Over 10 years, 61 men sustained non
      vertebral fragility fractures. After adjustment for age, BMI, hip BMD, abdominal
      aortic calcifications and prior falls and fractures, the non-vertebral fracture
      risk decreased with increasing DSN score. The risk of non-vertebral fracture was
      half as high in men above the median total DSN score vs men below the median.
      CONCLUSION: In older men, severe DD is associated with higher BMD. Multilevel
      severe DSN is associated with higher vertebral fracture risk and lower non
      vertebral fracture risk.

PMID- 27703043
TI  - Low-anxiety rats are more sensitive to amphetamine in comparison to high-anxiety
      rats.
AB  - This study utilised the two injection protocol of sensitisation (TIPS) and the
      conditioned place preference test to validate and extend previous findings on the
      effects of amphetamine on positive reinforcement-related 50 kHz ultrasonic
      vocalisation (USV) in rats. We also examined changes in the expression of c-Fos
      and the NMDA receptor 2B (GluN2B) subunit, markers of neuronal activity and
      plasticity, in brain regions of rats in response to TIPS. We used low anxiety
      responsive (LR) and high anxiety-responsive (HR) rats, which are known to exhibit
      different fear-conditioned response strengths, different susceptibilities to
      amphetamine in the TIPS procedure and different amphetamine-dependent 50 kHz USV
      responses. The LR rats, compared to the HR rats, not only vocalised much more
      intensely but also spent significantly more time in the amphetamine-paired
      compartment. After the second dose of amphetamine, the LR rats exhibited more c
      Fos and GluN2B activation in layers II and III of the M1/M2 motor cortex area and
      prefrontal cortex (PRE, PRL, IL) and also presented with more GluN2B activation
      in the basal amygdala. These data reveal that HR and LR rats exhibit different
      levels of reactivity in the cortical-limbic pathway, which controls reward
      related motivational processes. These findings contribute to the general
      hypothesis that heterogeneity in emotional processes is one of the causes of
      sensitisation to amphetamine and drug addiction.

PMID- 27703049
TI  - Detection of Genomic DNA Damage from Radiated Nasopharyngeal Carcinoma Cells
      Using Surface-Enhanced Raman Spectroscopy (SERS).
AB  - Structural changes and chemical modifications in DNA during interactions with X
      ray radiation are still not clear within 48 h of incubation. We investigate
      genomic DNA from the radiated CNE2 cell line within 48 h of incubation using
      surface-enhanced Raman spectroscopy (SERS). Multivariate methods including
      principal component analysis (PCA) and random forest are proposed to explore the
      statistical significance before and after radiation. Our results show that
      intensities of several bands change after radiation, which indicates backbone
      damage and base-unstacking. Biological effects from DNA damage repairing process
      may be simultaneously stimulated and different from incubation time. Under doses
      of 10 Gy (with 24 and 48 h of incubation) and 20 Gy (with 48 h of incubation),
      the relative contents of C against T and A against G deviate obviously from the
      control level. Statistical results strengthen significantly the idea that
      modification in DNA bases is associated with the disruption of base-stacking in
      the DNA duplex. Our findings provide vital information for radiation-induced the
      DNA damage at the molecular level, which may provide insight into the effect and
      mechanism of anticarcinogens in tumor therapy.

PMID- 27703050
TI  - Synchrotron-Based Three-Dimensional Fourier-Transform Infrared Spectro
      Microtomography of Murchison Meteorite Grain.
AB  - We demonstrate nondestructive, three-dimensional, microscopic, infrared (IR)
      spectral in-situ imaging of an extraterrestrial sample. Spatially resolved
      chemical composition and spatial correlations are investigated within a single 45
      um grain of the Murchison meteorite. Qualitative and quantitative investigation
      through this analytical technique can help elucidate the origin and evolution of
      meteoritic compounds as well as parent body processes without damaging or
      altering the investigated samples.

PMID- 27703042
TI  - The ICCAM platform study: An experimental medicine platform for evaluating new
      drugs for relapse prevention in addiction. Part B: fMRI description.
AB  - OBJECTIVES: We aimed to set up a robust multi-centre clinical fMRI and
      neuropsychological platform to investigate the neuropharmacology of brain
      processes relevant to addiction - reward, impulsivity and emotional reactivity.
      Here we provide an overview of the fMRI battery, carried out across three
      centres, characterizing neuronal response to the tasks, along with exploring
      inter-centre differences in healthy participants. EXPERIMENTAL DESIGN: Three fMRI
      tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go
      to probe impulsivity and an evocative images task to probe emotional reactivity.
      A coordinate-based activation likelihood estimation (ALE) meta-analysis was
      carried out for the reward and impulsivity tasks to help establish region of
      interest (ROI) placement. A group of healthy participants was recruited from
      across three centres (total n=43) to investigate inter-centre differences.
      Principle observations: The pattern of response observed for each of the three
      tasks was consistent with previous studies using similar paradigms. At the whole
      brain level, significant differences were not observed between centres for any
      task. CONCLUSIONS: In developing this platform we successfully integrated
      neuroimaging data from three centres, adapted validated tasks and applied whole
      brain and ROI approaches to explore and demonstrate their consistency across
      centres.

PMID- 27703051
TI  - Application of SLICC classification criteria in undifferentiated connective
      tissue disease and evolution in systemic lupus erythematosus: analysis of a large
      monocentric cohort with a long-term follow-up.
AB  - Objectives The objectives of this study were to analyse the performance of the
      Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification
      criteria for systemic lupus erythematosus (SLE) in a large cohort of
      undifferentiated connective tissue disease (UCTD) population at onset of the
      disease and during a long-term follow-up of 15 years (1999-2013) and to evaluate
      the transition from UCTD to SLE, according to American College of Rheumatology
      (ACR) 1997 and SLICC 2012 classification criteria. Methods A cohort of patients
      who met the classification criteria proposed by Mosca et al. for UCTD, were
      analysed. The SLICC 2012 classification criteria for SLE were retrospectively
      applied to each patient at the time of the diagnosis (T0) and also periodically
      re-applied and compared to ACR 1997 criteria at three different time points in
      the follow-up. Results 329 patients were enrolled. According to inclusion
      criteria at T0 no patient met the SLE/ACR criteria, whilst, retrospectively
      applying the SLE/SLICC criteria, 44 patients already satisfied this set of
      criteria for SLE. During the follow-up 23 new patients reached the SLE/SLICC
      criteria and 14 patients met the ACR criteria with a stable rate of progression
      to SLE over time. Acute or subacute skin rash, antiphospholipid antibody (aPL)
      positivity and serositis were the variables correlated to the evolution to SLE.
      Conclusions In our UCTD population, the application of SLICC classification
      criteria for SLE at disease onset allowed identification of a proportion of
      otherwise missed SLE cases; during follow-up, and compared with ACR criteria,
      SLICC criteria expanded the number of patients classifiable as SLE otherwise
      classified as UCTD.

PMID- 27703052
TI  - Disseminated cytomegalovirus infection complicating active treatment of systemic
      lupus erythematosus: an emerging problem.
AB  - Patients with systemic lupus erythematosus (SLE) often require immunosuppression
      to induce remission of active disease exacerbations. Over the past two decades,
      treatment modalities for this condition have emerged leading to improved
      morbidity from disease related outcomes. However, as a result, infection risks
      and patterns have changed, leading to higher rates of opportunistic infections
      among this population. We report four cases of cytomegalovirus (CMV) in patients
      with SLE who received immunosuppressive therapy, including pulse steroids,
      antimetabolites such as mycophenolate mofetil, and alkylating agents such as
      cyclophosphamide. We propose that given the rise in prevalence of CMV, there is a
      need for appropriate screening for this opportunistic pathogen and studies to
      determine the risks and benefits of prophylactic or preemptive treatment for this
      virus.

PMID- 27703054
TI  - Estimating shifts in diversification rates based on higher-level phylogenies.
AB  - Macroevolutionary studies recently shifted from only reconstructing the past
      state, i.e. the species phylogeny, to also infer the past speciation and
      extinction dynamics that gave rise to the phylogeny. Methods for estimating
      diversification dynamics are sensitive towards incomplete species sampling. We
      introduce a method to estimate time-dependent diversification rates from
      phylogenies where clades of a particular age are represented by only one sampled
      species. A popular example of this type of data is phylogenies on the genus- or
      family-level, i.e. phylogenies where one species per genus or family is included.
      We conduct a simulation study to validate our method in a maximum-likelihood
      framework. Further, this method has already been introduced into the Bayesian
      package MrBayes, which led to new insights into the evolution of Hymenoptera.

PMID- 27703053
TI  - Gestational weight gain in women with systemic lupus erythematosus.
AB  - Objective The objective of this study was to estimate the proportion of pregnant
      women with systemic lupus erythematosus meeting Institute of Medicine guidelines
      for gestational weight gain and determine correlates of adherence to guidelines.
      Methods Singleton, live births in the Hopkins Lupus Pregnancy Cohort 1987-2015
      were included. Pre-pregnancy weight was the weight recorded 12 months prior to
      pregnancy/first trimester. Final weight was the last weight recorded in the third
      trimester. Adherence to Institute of Medicine guidelines (inadequate, adequate,
      or excessive) was based on pre-pregnancy body mass index. Fisher's exact test and
      analysis of variance determined factors associated with not meeting guidelines.
      Stepwise selection estimated predictors of gestational weight gain. Results Of
      the 211 pregnancies, 34%, 24% and 42% had inadequate, adequate and excessive
      gestational weight gain, respectively. In exploratory analyses, differences in
      Institute of Medicine adherence were observed by pre-pregnancy body mass index,
      race, elevated creatinine during pregnancy and pre-pregnancy blood pressure. Odds
      of inadequate and excessive gestational weight gain increased 12% with each 1
      kg/m2 increase in pre-pregnancy body mass index. Lower maternal education was
      associated with increased odds of inadequate and excessive gestational weight
      gain. Conclusions As in the general population, most women with systemic lupus
      erythematosus did not meet Institute of Medicine guidelines. Our results
      identified predictors of gestational weight gain to aid in targeted interventions
      to improve guideline adherence in this population.

PMID- 27703055
TI  - Long-distance autumn migration across the Sahara by painted lady butterflies:
      exploiting resource pulses in the tropical savannah.
AB  - The painted lady, Vanessa cardui, is a migratory butterfly that performs an
      annual multi-generational migration between Europe and North Africa. Its seasonal
      appearance south of the Sahara in autumn is well known and has led to the
      suggestion that it results from extremely long migratory flights by European
      butterflies to seasonally exploit the Sahel and the tropical savannah. However,
      this possibility has remained unproven. Here, we analyse the isotopic composition
      of butterflies from seven European and seven African countries to provide new
      support for this hypothesis. Each individual was assigned a geographical natal
      origin, based on its wing stable hydrogen isotope (delta2Hw) value and a
      predicted delta2Hw basemap for Europe and northern Africa. Natal assignments of
      autumn migrants collected south of the Sahara confirmed long-distance movements
      (of 4000 km or more) starting in Europe. Samples from Maghreb revealed a mixed
      origin of migrants, with most individuals with a European origin, but others
      having originated in the Sahel. Therefore, autumn movements are not only directed
      to northwestern Africa, but also include southward and northward flights across
      the Sahara. Through this remarkable behaviour, the productive but highly seasonal
      region south of the Sahara is incorporated into the migratory circuit of V.
      cardui.

PMID- 27703056
TI  - Yawn duration predicts brain weight and cortical neuron number in mammals.
AB  - Research indicates that the motor action pattern of yawning functions to promote
      cortical arousal and state change through enhanced intracranial circulation and
      brain cooling. Because the magnitude of this response likely corresponds to the
      degree of neurophysiological change, we hypothesized that interspecies variation
      in yawn duration would correlate with underlying neurological differences. Using
      openly accessible data, we show that both the mean and variance in yawn duration
      are robust predictors of mammalian brain weight and cortical neuron number (rho
      values > 0.9). Consistent with these effects, primates tend to have longer and
      more variable yawn durations compared with other mammals. Although yawning has
      long been considered a stereotyped action pattern, these findings reveal
      substantial variation in this response and highlight the importance of measuring
      yawn duration in future research.

PMID- 27703057
TI  - Increase in disaster-related deaths: risks and social impacts of evacuation.
AB  - In Fukushima Prefecture, disaster-related death is a social problem for
      individuals who were forced to leave their hometowns as a result of the Great
      East Japan Earthquake and the accident at Fukushima Daiichi nuclear power plant.
      Disaster-related death is caused by stress, exhaustion, and worsening of pre
      existing illnesses due to evacuation. The number of disaster-related deaths has
      reached almost 2000, and continues to rise. Prolonged uncertainty and
      deteriorating living conditions suggest no end to such deaths, although response
      measures have been taken to improve the situation. It is said that insufficient
      response measures were taken, in particular, during the transitional period
      between the emergency phase and the reconstruction phase. There is a need to
      apply the lessons learned in planning for evacuation after a nuclear hazard,
      considering radiological protection as well as risks associated with evacuation.

PMID- 27703059
TI  - Health Policy Initiatives for African American Women Veterans.
AB  - America's military has experienced great changes in the demographic makeup of its
      veterans over the past few decades. In fact, the fastest growing group in the
      U.S. military is women. This demographic trend has also brought new challenges in
      dealing with gender issues, something that the Veterans Health Administration
      (VHA) has only recently begun to acknowledge. The VHA has responded in several
      ways to gender issues in health care and health outcomes. And, although the VHA
      is dealing with multiple gender matters, this article will focus on initiatives
      to combat cardiovascular disease (CVD) in women veterans. It will also highlight
      the significance of CVD, both to women veterans in general and to African
      American women veterans specifically. The article concludes with a discussion of
      VHA activities and strategies to improve the cardiovascular health of African
      American women veterans.

PMID- 27703058
TI  - Distribution of ESBLs, AmpC beta-lactamases and carbapenemases among
      Enterobacteriaceae isolates causing intra-abdominal and urinary tract infections
      in the Asia-Pacific region during 2008-14: results from the Study for Monitoring
      Antimicrobial Resistance Trends (SMART).
AB  - OBJECTIVES: To investigate the antimicrobial resistance and assess the molecular
      characteristics of beta-lactamases (ESBLs, AmpC beta-lactamases and
      carbapenemases) among Enterobacteriaceae isolates that caused intra-abdominal
      infections (IAIs) in patients hospitalized in the Asia-Pacific region during 2008
      14. METHODS: Multiplex PCR was used to detect the specific types of beta
      lactamase in 2893 isolates with MICs of ertapenem >0.5 mg/L. In-hospital
      acquisition times for most isolates were also delineated. RESULTS: Among 2728
      (94.3%) isolates proven with beta-lactamase production, the rates of non
      susceptibility to imipenem were low (average = 7.9%) among IAI Enterobacteriaceae
      isolates from all Asia-Pacific countries except Vietnam (17.7%) and the
      Philippines (10.2%). A stepwise and significant increase in annual rates of
      carbapenemase production among these isolates was noted. CTX-M-15 and CTX-M-14
      were the dominant ESBL variants in most IAI Enterobacteriaceae species. The most
      abundant AmpC beta-lactamase variants were blaCMY-2 among isolates of Escherichia
      coli and blaDHA-1 among isolates of Klebsiella pneumoniae. In addition, the IAI
      Enterobacteriaceae isolates harbouring a blaCMY-2 or blaDHA-1 allele were
      associated with high community-acquired rates (38.0% and 42.6%, respectively).
      AmpC ACT and MIR variants were mostly detected in Enterobacter species. The
      blaNDM-1,4,5,7-harbouring isolates of E. coli, K. pneumoniae and Enterobacter
      cloacae were most commonly identified among IAI isolates from Vietnam and the
      Philippines. Also of note, blaOXA-48-harbouring IAI Enterobacteriaceae isolates
      were detected exclusively in Vietnam. CONCLUSIONS: The high resistance burden in
      Vietnam and the Philippines warrants aggressive control policies to combat the
      worsening trend in antimicrobial resistance among Enterobacteriaceae species
      causing IAIs.

PMID- 27703061
TI  - Olfactory Training Using Heavy and Light Weight Molecule Odors.
AB  - Background Repeated short-term exposure to odors is known to improve olfaction in
      patients with acquired olfactory dysfunction. The aim was to find out whether
      differences in molecular weight of odors used for olfactory training influences
      olfaction. We hypothesized a greater improvement following training with light
      weight molecule (LWM) odors. Methods A prospective study was performed in
      patients with posttraumatic (PTOL) and postviral olfactory loss (PVOL). Olfactory
      training was performed over a period of 5 months. One group ( n = 48) used four
      odors containing heavy weight molecules (HWM; >150 g/mol) and another ( n = 48)
      containing LWM (<150 g/mol). Olfaction was tested before and after the training
      using the Sniffin' Sticks test. Results Olfactory training was associated with
      olfactory improvement, with the improvement in PVOL patients being three times
      greater than that seen in the PTOL group. Compared with LWM training, HWM
      training was associated with a significantly greater improvement in Phenyl Ethyl
      Alcohol (PEA) threshold scores in PVOL patients; however, no such improvement
      could be shown for other subtests or in PTOL patients. Conclusion Overall,
      training was associated with olfactory improvement. With the exception of
      threshold scores in PVOL, there were no significant differences between LWM and
      HWM groups.

PMID- 27703062
TI  - Multivariate Associations Among Health-Related Fitness, Physical Activity, and
      TGMD-3 Test Items in Disadvantaged Children From Low-Income Families.
AB  - Motor skills are needed for physical development and may be linked to health
      related fitness and physical activity levels. No studies have examined the
      relationships among these constructs in large samples of disadvantaged children
      from low-income families using the Test for Gross Motor Development-3rd Edition
      (TGMD-3). The purpose of this study was to examine the multivariate associations
      among health-related fitness, physical activity, and motor skills assessed using
      the TGMD-3. Participants included 1460 school-aged children (730 boys, 730 girls;
      M age = 8.4 years, SD = 1.8 years) recruited from the K to sixth grades from
      three low-income schools. Health-related fitness was assessed using the
      FITNESSGRAM battery, physical activity was assessed using accelerometers and
      pedometers, and motor skills were assessed using the TGMD-3. Canonical
      correlations revealed statistically significant correlations between the Ball
      Skills and health-related fitness variates (Rc = 0.43, Rc2 = 17%, p < 0.001).
      Significant canonical coefficients in the Ball Skills variate included two-handed
      striking, dribbling, and catching, and significant canonical coefficients in the
      health-related fitness variate included body mass index and the progressive
      aerobic cardiovascular endurance run ( p < 0.01). Locomotor skills did not
      significantly correlate with health-related fitness or physical activity. Ball
      skills are related to health-related fitness in disadvantaged children from low
      income families.

PMID- 27703060
TI  - Quantitative assessment of parent vessel and distal intracranial hemodynamics
      following pipeline flow diversion.
AB  - Background Pipeline embolization devices (PEDs) are commonly used for
      endovascular treatment of cerebral aneurysms but can be associated with delayed
      ipsilateral intraparenchymal hemorrhage. Although intra-aneurysmal hemodynamic
      changes have been studied, parent vessel and intracranial hemodynamics after PED
      use are unknown. We examine the impact of flow diversion on parent artery and
      distal intracranial hemodynamics. Method Patients with internal carotid cerebral
      aneurysms treated with PED who had flow volume rate, flow velocities, pulsatility
      index, resistance index, Lindegaard ratio, and wall shear stress (WSS) obtained
      after treatment using quantitative magnetic resonance angiography were reviewed.
      Means were compared between ipsilateral and contralateral internal carotid artery
      (ICA) and middle cerebral artery (MCA) using paired t tests. Results A total of
      18 patients were included. Mean flow volume rate was lower in the ipsilateral
      versus contralateral ICA ( p = 0.04) but tended to be higher in the ipsilateral
      versus contralateral MCA ( p = 0.08). Lindegaard ratio was higher ipsilateral to
      the PED in diastole ( p = 0.05). Although there was no significant difference in
      flow velocities, pulsatility or resistance indices, and WSS, the two cases in our
      cohort with hemorrhagic complications did display significant changes in MCA
      flows and MCA WSS. Conclusion PED placement appears to alter the elasticity of
      the stented ICA segment, with lower flows in the ipsilateral versus contralateral
      ICA. Conversely, MCA flows and MCA WSS are higher in the ipsilateral MCA among
      patients with hemorrhage after PED placement, suggesting the role of disrupted
      distal hemodynamics in delayed ipsilateral intraparenchymal hemorrhage.

PMID- 27703063
TI  - Speed of Reaction and Fighting Effectiveness in Elite Greco-Roman Wrestlers.
AB  - The purpose of the study was to determine the changes in simple reaction time and
      to define correlations between simple reaction time and technical and tactical
      actions performed by elite Greco-Roman wrestlers during a match. Twenty Greco
      Roman wrestlers (M age = 19.5 years, SD = 1.8) from the Wrestling Sports Centre
      in Radom participated in the study. Simple reaction time (including reaction time
      and movement time) before a match and after the first, the second, and the third
      round was analyzed. The wrestlers' reaction time and movement time changed in the
      course of performance. Wrestlers with higher sports achievements demonstrated a
      smaller decrement in simple reaction time and performed more technical and
      tactical actions during a match. The strongest correlations were observed between
      both reaction time and movement time and the number of technical and tactical
      actions performed during the last round. Quick reaction was a significant factor
      in determining the match outcome, which is revealed at submaximal intensity of
      the effort during a match.

PMID- 27703064
TI  - Physical and Functional Impairment During and After Hospitalization in Subjects
      With Severe COPD Exacerbation.
AB  - BACKGROUND: COPD exacerbations are frequent events that have a negative impact on
      the lives of patients. The aims of this study were to analyze physical and
      functional impairment during hospital stay in subjects hospitalized due to COPD
      exacerbation and to assess the physical and functional impact of hospitalization
      at a 1-month follow-up in patients with severe COPD. METHODS: This was a
      prospective observational study on a sample of 52 subjects hospitalized due to
      COPD exacerbation. The assessments were performed at baseline, discharge, and 1
      month follow-up. The outcome measures were dyspnea, muscle strength, functional
      capacity, and postural steadiness. RESULTS: Quadriceps strength [1.036 (P = .043)
      kg mean difference] and the one-leg stance test [1.04 (P = .02) and 0.73 (P =
      .032) s mean difference right and left leg] showed significant impairment during
      hospitalization. Dyspnea perception improved significantly (P = .004) during
      hospitalization. Additionally, strength in the upper and lower limbs [4.04 (P =
      .002) and 1.23 (P = .038) kg mean difference], functional capacity [3.0 number of
      steps mean difference (P = .032)], and the one-leg stance test [2.12 (P = .006)
      and 0.53 (P = .047) s mean difference right and left leg] showed significant
      impairment 1-month follow-up. CONCLUSIONS: Hospitalization due to COPD
      exacerbation leads to physical and functional impairment in patients; impairment
      is greater at 1-month follow-up. It would be interesting to conduct physical
      therapy interventions to prevent the impairment.

PMID- 27703065
TI  - The prevalence of fatigue after stroke: A systematic review and meta-analysis.
AB  - BACKGROUND: Fatigue is a common and debilitating symptom after stroke. The last
      decade has seen rapid expansion of the research literature on post-stroke
      fatigue, but prevalence remains unclear. AIMS: To estimate post-stroke fatigue
      prevalence and to identify the contributing factors to fatigue, by conducting a
      systematic review and meta-analysis. SUMMARY OF REVIEW: We included all studies
      of adult stroke survivors that used a recognized assessment scale for fatigue
      (search date September 2014). Two reviewers independently reviewed all full texts
      for inclusion. Data were extracted by one reviewer and independently cross
      checked by a second. Risk of bias was evaluated using a critical appraisal tool.
      From an overall yield of 921 studies, 101 full text papers were screened, and 49
      of these met inclusion criteria. The most widely used measure of fatigue was the
      Fatigue Severity Scale (n = 24 studies). Prevalence estimates at a cut-off score
      of > or >= 4 were available for 22 of these 24 studies (total n = 3491), and
      ranged from 25 to 85%. In random effects meta-analysis, the pooled prevalence
      estimate was 50% (95% CI 43-57%), with substantial heterogeneity (I2 = 94%).
      Neither depression status nor time point post-stroke explained the heterogeneity
      between studies. In post-hoc analysis, fatigue prevalence was found to be lower
      in the four Asian studies (35%; 95% CI 20-50; I2 = 96%). CONCLUSIONS: Our results
      confirm that fatigue is a widespread issue for stroke survivors, although it may
      be less prevalent in Asia. Further research is needed to explain the wide
      variability in prevalence estimates between studies.

PMID- 27703066
TI  - Overcoming global challenges in stroke prophylaxis in atrial fibrillation: The
      role of non-vitamin K antagonist oral anticoagulants.
AB  - Atrial fibrillation is the world's most common sustained cardiac arrhythmia and
      is associated with a significantly increased risk of stroke. The global burden of
      atrial fibrillation is rising, commensurate with the ageing population. Well
      controlled vitamin K antagonist-based anticoagulation has been shown to reduce
      the risk of stroke secondary to atrial fibrillation by two-thirds. However,
      patients with atrial fibrillation have frequently been denied anticoagulation
      because of a variety of perceived risks related to bleeding, falls, chronological
      age, and poor compliance. Even when vitamin K antagonists are used, maximum
      benefit and safety are only delivered when high quality control of therapy (TTR >
      70%) is achieved, which has proven remarkably difficult in many health-care
      systems and amongst many patient groups. The non-vitamin K antagonist oral
      anticoagulants (NOACs) offer solutions to many of the challenges of achieving
      widespread, safe, and effective anticoagulation for stroke prophylaxis in atrial
      fibrillation, yet their uptake into routine clinical practice remains variable.
      The evidence supporting their more widespread use to overcome the challenges of
      stroke prophylaxis for atrial fibrillation is reviewed in this article.

PMID- 27703067
TI  - Fibrin gel versus papain gel in the healing of chronic venous ulcers: A double
      blind randomized controlled trial.
AB  - Objectives Compare the efficacy and safety of fibrin gel to 8% papain gel for
      wound dressing of venous ulcers. Method Patients with chronic venous ulcers were
      randomly assigned to one in three groups: Group 1-fibrin gel; Group 2-8% papain
      gel; Group 3-carbopol gel (control). Patients were seen every 15 days during 2
      months, verifying reduction of the ulcer area, local infection, exudation, and
      epithelization. All serious or nonserious adverse events were recorded. Results
      Fifty-five patients (total of 63 ulcers) were randomly distributed in three
      groups (G1 = 21; G2 = 19; G3 = 23). No patient was excluded or discontinued
      treatment throughout the study. The areas of the ulcers were similarly reduced in
      all groups (14.3%, 21.1%, and 30.4% in groups 1, 2, and 3, respectively), and all
      had significant reduction in exudation and contamination. Conclusion The data
      demonstrate that neither fibrin gel nor papain gel were able to improve the
      process of ulcer-healing, as compared to control.

PMID- 27703068
TI  - Hospital incidence and annual rates of hospitalization for venous thromboembolic
      disease in France and the USA.
AB  - Objective The study was designed to describe the hospital incidences and annual
      hospitalization rates for venous thromboembolic disease by age and sex in France
      and the United States on the closest possible methodological bases. Methods
      French statistics are from the PMSI MCO (Programme de medicalisation des systeme
      d'information de medecine, chirurgie et obstetrique (French national hospital
      discharge register)) national database. These are compiled for each calendar year
      by collating resume de sortie anonymise (RSA, anonymous discharge summary) files
      forwarded and validated by health establishments with admissions in medicine,
      surgery, obstetrics, and odontology. They are compared to the data issued from
      the US National Hospital Discharge Survey which is equivalent to the PMSI in
      France and uses the International Classification of Diseases-9 for encoding the
      data. These data were published in the Morbidity, Mortality Weekly Report of the
      Centre for Disease Control. Results In the US, 547,996 hospital stays involve
      venous thromboembolic diseases, 348,558 deep venous thrombosis (DVT), and 277,549
      pulmonary embolism (PE). Of these 78,511, or 14%, include a diagnosis of both DVT
      and PE. The hospital incidence of venous thromboembolic disease is 1.4%, DVT
      0.9%, and PE 0.7%. In France, of the 26,658,228 annual hospital stays, 273,931
      include venous thromboembolic disease, 179,286 DVT, and 139,345 PE while 44,700,
      i.e. 16.3%, include both DVT and PE. The hospital incidence of venous
      thromboembolic disease is thus 1.0%, DVT 0.6%, and PE 0.5%. The overall annual
      hospitalization rates for venous thromboembolic disease, DVT, and PE are
      respectively 274, 179, and 139 per 100,000 inhabitants in France and 239, 146,
      and 121 per 100,000 inhabitants in the US. Conclusion Venous thromboembolic
      diseases occur in France and the US in 1% of all hospital stays and are
      responsible for an annual hospitalization rate that exceeds 200 per 100,000. The
      scale of these annual incidences should prompt us to question the quality of
      prevention put in place and/or its efficacy.

PMID- 27703069
TI  - Secondhand Smoke Exposure 7 Years After an Indoor Smoke-Free Law.
AB  - PURPOSE: To examine locations of secondhand smoke (SHS) exposure among
      nonsmokers, 7 years after a statewide smoke-free policy. DESIGN: Data collected
      via statewide, random digit dial telephone survey. Response rates were 64.7% for
      landline and 73.5% for cell phone. SETTING: Minnesota, 2014. PARTICIPANTS:
      Representative sample of 7887 nonsmoking adults. MEASURES: Self-reported
      locations of SHS exposure and opinions on smoke-free restrictions. ANALYSIS:
      Descriptive statistics and logistic regression. RESULTS: A total of 35.5% of
      nonsmokers reported SHS exposure in the past 7 days. The greatest proportion of
      exposure occurred in community settings (31.7%) followed by cars (6.9%) and in
      the home (3.2%). Young adults were more likely to be exposed in a home or car
      than older adults. Nonsmokers living with a smoker were 39.6 (20.6-75.8) times
      more likely to be exposed to SHS in their home and 5.3 (4.1-6.8) times more
      likely to be exposed in a car, compared to those who did not live with a smoker.
      CONCLUSION: SHS exposure continues after comprehensive smoke-free policies
      restricted it from public places. Disparities in exposure rates exist for those
      who live with a smoker, are young, and have low incomes. Findings suggest the
      need for additional policies that will have the greatest public health benefit.

PMID- 27703070
TI  - Cap0037, a Novel Global Regulator of Clostridium acetobutylicum Metabolism.
AB  - : An operon comprising two genes, CA_P0037 and CA_P0036, that encode proteins of
      unknown function that were previously shown to be highly expressed in acidogenic
      cells and repressed in solventogenic and alcohologenic cells is located on the
      pSOL1 megaplasmid of Clostridium acetobutylicum upstream of adhE2 A CA_P0037::int
      (189/190s) mutant in which an intron was inserted at position 189/190 in the
      sense strand of CA_P0037 was successfully generated by the Targetron technique.
      The resultant mutant showed significantly different metabolic flux patterns in
      acidogenic (producing mainly lactate, butyrate, and butanol) and alcohologenic
      (producing mainly butyrate, acetate, and lactate) chemostat cultures but not in
      solventogenic or batch cultures. Transcriptomic investigation of the
      CA_P0037::int (189/190s) mutant showed that inactivation of CA_P0037
      significantly affected the expression of more than 258 genes under acidogenic
      conditions. Surprisingly, genes belonging to the Fur regulon, involved in iron
      transport (CA_C1029-CA_C1032), or coding for the main flavodoxin (CA_C0587) were
      the most significantly expressed genes under all conditions, whereas fur (coding
      for the ferric uptake regulator) gene expression remained unchanged. Furthermore,
      most of the genes of the Rex regulon, such as the adhE2 and ldhA genes, and of
      the PerR regulon, such as rbr3A-rbr3B and dfx, were overexpressed in the mutant.
      In addition, the whole CA_P0037-CA_P0036 operon was highly expressed under all
      conditions in the CA_P0037::int (189/190s) mutant, suggesting a self-regulated
      expression mechanism. Cap0037 was shown to bind to the CA_P0037-CA_P0036 operon,
      sol operon, and adc promoters, and the binding sites were determined by DNA
      footprinting. Finally, a putative Cap0037 regulon was generated using a
      bioinformatic approach. IMPORTANCE: Clostridium acetobutylicum is well-known for
      its ability to produce solvents, especially n-butanol. Understanding the
      regulatory network of C. acetobutylicum will be crucial for further engineering
      to obtain a strain capable of producing n-butanol at high yield and selectivity.
      This study has discovered that the Cap0037 protein is a novel regulator of C.
      acetobutylicum that drastically affects metabolism under both acidogenic and
      alcohologenic fermentation conditions. This is pioneering work for further
      determining the regulatory mechanism of Cap0037 in C. acetobutylicum and studying
      the role of proteins homologous to Cap0037 in other members of the phylum
      Firmicutes.

PMID- 27703071
TI  - Next-Generation High-Throughput Functional Annotation of Microbial Genomes.
AB  - Host infection by microbial pathogens cues global changes in microbial and host
      cell biology that facilitate microbial replication and disease. The complete maps
      of thousands of bacterial and viral genomes have recently been defined; however,
      the rate at which physiological or biochemical functions have been assigned to
      genes has greatly lagged. The National Institute of Allergy and Infectious
      Diseases (NIAID) addressed this gap by creating functional genomics centers
      dedicated to developing high-throughput approaches to assign gene function. These
      centers require broad-based and collaborative research programs to generate and
      integrate diverse data to achieve a comprehensive understanding of microbial
      pathogenesis. High-throughput functional genomics can lead to new therapeutics
      and better understanding of the next generation of emerging pathogens by rapidly
      defining new general mechanisms by which organisms cause disease and replicate in
      host tissues and by facilitating the rate at which functional data reach the
      scientific community.

PMID- 27703073
TI  - Mycobacteriophages as Incubators for Intein Dissemination and Evolution.
AB  - : Inteins are self-splicing protein elements that are mobile at the DNA level and
      are sporadically distributed across microbial genomes. Inteins appear to be
      horizontally transferred, and it has been speculated that phages may play a role
      in intein distribution. Our attention turns to mycobacteriophages, which infect
      mycobacteria, where both phage and host harbor inteins. Using bioinformatics,
      mycobacteriophage genomes were mined for inteins. This study reveals that these
      mobile elements are present across multiple mycobacteriophage clusters and are
      pervasive in certain genes, like the large terminase subunit TerL and a RecB-like
      nuclease, with the majority of intein-containing genes being phage specific.
      Strikingly, despite this phage specificity, inteins localize to functional motifs
      shared with bacteria, such that intein-containing genes have similar roles, like
      hydrolase activity and nucleic acid binding, indicating a global commonality
      among intein-hosting proteins. Additionally, there are multiple insertion points
      within active centers, implying independent invasion events, with regulatory
      implications. Several phage inteins were shown to be splicing competent and to
      encode functional homing endonucleases, important for mobility. Further,
      bioinformatic analysis supports the potential for phages as facilitators of
      intein movement among mycobacteria and related genera. Analysis of catalytic
      intein residues finds the highly conserved penultimate histidine inconsistently
      maintained among mycobacteriophages. Biochemical characterization of a
      noncanonical phage intein shows that this residue influences precursor
      accumulation, suggesting that splicing has been tuned in phages to modulate
      generation of important proteins. Together, this work expands our understanding
      of phage-based intein dissemination and evolution and implies that phages provide
      a context for evolution of splicing-based regulation. IMPORTANCE: Inteins are
      mobile protein splicing elements found in critical genes across all domains of
      life. Mycobacterial inteins are of particular interest because of their
      occurrence in pathogenic species, such as Mycobacterium tuberculosis and
      Mycobacterium leprae, which harbor inteins in important proteins. We have
      discovered a similarity in activities of intein-containing proteins among
      mycobacteriophages and their intein-rich actinobacterial hosts, with implications
      for both posttranslational regulation by inteins and phages participating in
      horizontal intein transfer. Our demonstration of multiple insertion points within
      active centers of phage proteins implies independent invasion events, indicating
      the importance of intein maintenance at specific functional sites. The variable
      conservation of a catalytic splicing residue, leading to profoundly altered
      splicing rates, points to the regulatory potential of inteins and to
      mycobacteriophages playing a role in intein evolution. Collectively, these
      results suggest inteins as posttranslational regulators and mycobacteriophages as
      both vehicles for intein distribution and incubators for intein evolution.

PMID- 27703072
TI  - LasR Variant Cystic Fibrosis Isolates Reveal an Adaptable Quorum-Sensing
      Hierarchy in Pseudomonas aeruginosa.
AB  - : Chronic Pseudomonas aeruginosa infections cause significant morbidity in
      patients with cystic fibrosis (CF). Over years to decades, P. aeruginosa adapts
      genetically as it establishes chronic lung infections. Nonsynonymous mutations in
      lasR, the quorum-sensing (QS) master regulator, are common in CF. In laboratory
      strains of P. aeruginosa, LasR activates transcription of dozens of genes,
      including that for another QS regulator, RhlR. Despite the frequency with which
      lasR coding variants have been reported to occur in P. aeruginosa CF isolates,
      little is known about their consequences for QS. We sequenced lasR from 2,583 P.
      aeruginosa CF isolates. The lasR sequences of 580 isolates (22%) coded for
      polypeptides that differed from the conserved LasR polypeptides of well-studied
      laboratory strains. This collection included 173 unique lasR coding variants, 116
      of which were either missense or nonsense mutations. We studied 31 of these
      variants. About one-sixth of the variant LasR proteins were functional, including
      3 with nonsense mutations, and in some LasR-null isolates, genes that are LasR
      dependent in laboratory strains were nonetheless expressed. Furthermore, about
      half of the LasR-null isolates retained RhlR activity. Therefore, in some CF
      isolates the QS hierarchy is altered such that RhlR quorum sensing is independent
      of LasR regulation. Our analysis challenges the view that QS-silent P. aeruginosa
      is selected during the course of a chronic CF lung infection. Rather, some lasR
      sequence variants retain functionality, and many employ an alternate QS strategy
      involving RhlR. IMPORTANCE: Chronic Pseudomonas aeruginosa infections, such as
      those in patients with the genetic disease cystic fibrosis, are notable in that
      mutants with defects in the quorum-sensing transcription factor LasR frequently
      arise. In laboratory strains of P. aeruginosa, quorum sensing activates
      transcription of dozens of genes, many of which encode virulence factors, such as
      secreted proteases and hydrogen cyanide synthases. In well-studied laboratory
      strains, LasR-null mutants have a quorum-sensing-deficient phenotype. Therefore,
      the presence of LasR variants in chronic infections has been interpreted to
      indicate that quorum-sensing-regulated products are not important for those
      infections. We report that some P. aeruginosa LasR variant clinical isolates are
      not LasR-null mutants, and others have uncoupled a second quorum-sensing system,
      the RhlR system, from LasR regulation. In these uncoupled isolates, RhlR
      independently activates at least some quorum-sensing-dependent genes. Our
      findings suggest that quorum sensing plays a role in chronic P. aeruginosa
      infections, despite the emergence of LasR coding variants.

PMID- 27703074
TI  - Phosphorylation of Golgi Peripheral Membrane Protein Grasp65 Is an Integral Step
      in the Formation of the Human Cytomegalovirus Cytoplasmic Assembly Compartment.
AB  - : Human cytomegalovirus (HCMV) is the largest member of the Herpesviridae and
      represents a significant cause of disease. During virus replication, HCMV alters
      cellular functions to facilitate its replication, including significant
      reorganization of the secretory and endocytic pathways of the infected cell. A
      defining morphologic change of the infected cell is the formation of a membranous
      structure in the cytoplasm that is designated the virion assembly compartment
      (AC), which consists of virion structural proteins surrounded by cellular
      membranes. The loss of normal Golgi compartment morphology and its relocalization
      from a juxtanuclear ribbonlike structure to a series of concentric rings on the
      periphery of the AC represents a readily recognized reorganization of cellular
      membranes in the HCMV-infected cell. Although trafficking of viral proteins to
      this compartment is required for the assembly of infectious virions, the
      functional significance of the reorganization of intracellular membranes like the
      Golgi membranes into the AC in the assembly of infectious virus remains
      understudied. In this study, we determined that Golgi membrane ribbon
      fragmentation increased during the early cytoplasmic phase of virion assembly and
      that Golgi membrane fragmentation in infected cells was dependent on the
      phosphorylation of an integral cis-Golgi protein, Grasp65. Inhibition of Golgi
      membrane fragmentation and of its reorganization into the AC resulted in
      decreased production of infectious particles and alteration of the incorporation
      of an essential protein into the envelope of the mature virion. These results
      demonstrated the complexity of the virus-host cell interactions required for
      efficient assembly of this large DNA virus. IMPORTANCE: The human cytomegalovirus
      (HCMV)-induced reorganization of intracellular membranes that is required for the
      formation of the viral assembly compartment (AC) has been an area of study over
      the last 20 years. The significance of this virus-induced structure has been
      evinced by the results of several studies which showed that relocalization of
      viral proteins to the AC was required for efficient assembly of infectious virus.
      In this study, we have identified a mechanism for the fragmentation of the Golgi
      ribbon in the infected cell en route to AC morphogenesis. Identification of this
      fundamental process during HCMV replication allowed us to propose that the
      functional role of Golgi membrane reorganization during HCMV infection was the
      concentration of viral structural proteins and subviral structures into a single
      intracellular compartment in order to facilitate efficient protein-protein
      interactions and the virion protein trafficking required for the assembly of this
      large and structurally complex virus.

PMID- 27703075
TI  - Collapse of Insect Gut Symbiosis under Simulated Climate Change.
AB  - : Global warming impacts diverse organisms not only directly but also indirectly
      via other organisms with which they interact. Recently, the possibility that
      elevated temperatures resulting from global warming may substantially affect
      biodiversity through disrupting mutualistic/parasitic associations has been
      highlighted. Here we report an experimental demonstration that global warming can
      affect a pest insect via suppression of its obligate bacterial symbiont. The
      southern green stinkbug Nezara viridula depends on a specific gut bacterium for
      its normal growth and survival. When the insects were reared inside or outside a
      simulated warming incubator wherein temperature was controlled at 2.5 degrees C
      higher than outside, the insects reared in the incubator exhibited severe fitness
      defects (i.e., retarded growth, reduced size, yellowish body color, etc.) and
      significant reduction of symbiont population, particularly in the midsummer
      season, whereas the insects reared outside did not. Rearing at 30 degrees C or
      32.5 degrees C resulted in similar defective phenotypes of the insects, whereas
      no adult insects emerged at 35 degrees C. Notably, experimental symbiont
      suppression by an antibiotic treatment also induced similar defective phenotypes
      of the insects, indicating that the host's defective phenotypes are attributable
      not to the heat stress itself but to the suppression of the symbiont population
      induced by elevated temperature. These results strongly suggest that high
      temperature in the midsummer season negatively affects the insects not directly
      but indirectly via the heat-vulnerable obligate bacterial symbiont, which
      highlights the practical relevance of mutualism collapse in this warming world.
      IMPORTANCE: Climate change is among the biggest environmental issues in the
      contemporary world, and its impact on the biodiversity and ecosystem is not only
      of scientific interest but also of practical concern for the general public. On
      the basis of our laboratory data obtained under strictly controlled environmental
      conditions and our simulated warming data obtained in seminatural settings
      (elevated 2.5 degrees C above the normal temperature), we demonstrate here that
      Nezara viridula, the notorious stinkbug pest, suffers serious fitness defects in
      the summer season under the simulated warming conditions, wherein high
      temperature acts on the insect not directly but indirectly via suppression of its
      obligate gut bacterium. Our finding highlights that heat-susceptible symbionts
      can be the "Achilles' heel" of symbiont-dependent organisms under climate change
      conditions.

PMID- 27703077
TI  - The Appraisal of Self-Care Agency Scale-Revised (ASAS-R): Reliability and
      Validity Among Older Chinese People.
AB  - The study aimed to test the reliability and validity of the Chinese version of
      the Appraisal of Self-Care Agency Scale-Revised (ASAS-R-CHI). A cross-sectional
      design was used to conduct this study, and the sample consisted of 1,219 older
      people, collected by a demographic questionnaire, ASAS-R-CHI and the Exercise of
      Self-Care Agency (ESCA) scale. The Cronbach's alpha (alpha) of ASAS-R-CHI was
      .79, the test-retest correlation was 0.95, and the item-to-total correlations
      ranged from r = .41 to r = .74. Exploratory factor analysis (EFA) resulted in
      three factors that explained 65.31% of the total variance; all 15 items had
      strong factor loadings ranging from 0.54 to 0.91. Confirmatory factor analysis
      (CFA) indicated the three-factor solution of ASAS-R-CHI had a good fit (x2,chi
      square/degree of freedom [CMIN/DF] = 2.61, goodness of fitness index [GFI] =
      0.93, adjusted goodness of fit index [AGFI] = 0.92,, comparative fit index [CFI =
      0.92], Tucker Lewis index [TLI] = 0.91, root mean square error of approximation
      [RMSEA] = 0.04, root mean residual [RMR] = 0.02, P-value for test of close fit
      [PCLOSE] = 0.68). ASAS-R-CHI is a short, reliable, and valid instrument for
      measuring self-care agency among Chinese older adults.

PMID- 27703076
TI  - Broadly Neutralizing Hemagglutinin Stalk-Specific Antibodies Induce Potent
      Phagocytosis of Immune Complexes by Neutrophils in an Fc-Dependent Manner.
AB  - : Broadly neutralizing antibodies that recognize the conserved hemagglutinin (HA)
      stalk have emerged as exciting new biotherapeutic tools to combat seasonal and
      pandemic influenza viruses. Our general understanding of the mechanisms by which
      stalk-specific antibodies achieve protection is rapidly evolving. It has recently
      been demonstrated that broadly neutralizing HA stalk-specific IgG antibodies
      require Fc-Fcgamma receptor (FcgammaR) interactions for optimal protection in
      vivo Here we examine the neutrophil effector functions induced by stalk-specific
      antibodies. As the most abundant subset of blood leukocytes, neutrophils
      represent a critical innate effector cell population and serve an instrumental
      role in orchestrating downstream adaptive responses to influenza virus infection.
      Yet, the interplay of HA stalk-specific IgG, Fc-FcgammaR engagement, and
      neutrophils has remained largely uncharacterized. Using an in vitro assay to
      detect the production of reactive oxygen species (ROS), we show that human and
      mouse monoclonal HA stalk-specific IgG antibodies are able to induce the
      production of ROS by neutrophils, while HA head-specific antibodies do not.
      Furthermore, our results indicate that the production of ROS is dependent on Fc
      receptor (FcR) engagement and phagocytosis. We went on to assess the ability of
      monoclonal HA stalk-specific IgA antibodies to induce ROS. Consistent with our
      findings for monoclonal IgGs, only HA stalk-specific IgA antibodies elicited ROS
      production by neutrophils. This induction is dependent on the engagement of
      FcalphaR1. Taken together, our findings describe a novel FcR-dependent effector
      function induced by HA stalk-specific IgG and IgA antibodies, and importantly,
      our studies shed light on the mechanisms by which HA stalk-specific antibodies
      achieve protection. IMPORTANCE: The present study provides evidence that broadly
      neutralizing HA stalk-specific antibodies induce downstream Fc-mediated
      neutrophil effector functions. In addition to their ability to neutralize, this
      class of antibodies has been shown to rely on Fc-Fc receptor interactions for
      optimal protection in vivo Curiously, neutralizing antibodies that bind the HA
      head domain do not require such interactions. Our findings build on these
      previous observations and provide a more complete picture of the relationship
      between stalk-specific antibodies and cells of the innate immune compartment.
      Furthermore, our data suggest that the ability of HA stalk-specific antibodies to
      mediate Fc-Fc receptor engagement is epitope dependent. Overall, this work will
      inform the rational design of improved influenza virus vaccines and therapeutics.

PMID- 27703078
TI  - The Influence of Social Structure on Cancer Pain and Quality of Life.
AB  - The aim of this study was to investigate whether social structure is associated
      with cancer pain and quality of life using the Social Structure and Personality
      Research Framework. This study was a secondary analysis of data from 480 cancer
      patients. The measurements included socioeconomic variables, self-reported cancer
      pain using the McGill Pain Questionnaire-Short Form (MPQ-SF), and quality of life
      measured using the Functional Assessment of Cancer Therapy Scale (FACT-G). The
      data were analyzed using moderated multiple regression. Cancer pain and quality
      of life differed significantly with income. The associations between income and
      pain and quality of life were significant only for the high education group (>=
      partial college), and these associations were greater for Caucasians than for
      their counterparts ( p < .05). When developing interventions, nurses should
      consider the influence of socioeconomic variables on pain and quality of life
      while considering possible moderating factors such as education.

PMID- 27703079
TI  - Formation and psychometric evaluation of a health-related quality of life
      instrument for children living with HIV in India.
AB  - In-depth interviews and focus group discussions were conducted to inform the
      development of an instrument to measure the health-related quality of life of
      children living with HIV. The QOL-CHAI instrument consists of four generic core
      scales of the "Pediatric Quality of Life Inventory" and two HIV-targeted scales
      "symptoms" and "discrimination." A piloting exercise involving groups of children
      living with HIV and HIV-negative children born to HIV-infected parents provided
      evidence for the acceptable psychometric properties and usability of the
      instrument. It is expected that the QOL-CHAI can serve well as a brief,
      standardized, and culturally appropriate instrument for assessing health-related
      quality of life of Indian children living with HIV.

PMID- 27703080
TI  - A Perspective on the Kinetics of Covalent and Irreversible Inhibition.
AB  - The clinical and commercial success of covalent drugs has prompted a renewed and
      more deliberate pursuit of covalent and irreversible mechanisms within drug
      discovery. A covalent mechanism can produce potent inhibition in a biochemical,
      cellular, or in vivo setting. In many cases, teams choose to focus on the
      consequences of the covalent event, defined by an IC50 value. In a biochemical
      assay, the IC50 may simply reflect the target protein concentration in the assay.
      What has received less attention is the importance of the rate of covalent
      modification, defined by kinact/KI. The kinact/KI is a rate constant describing
      the efficiency of covalent bond formation resulting from the potency (KI) of the
      first reversible binding event and the maximum potential rate (kinact) of
      inactivation. In this perspective, it is proposed that the kinact/KI should be
      employed as a critical parameter to identify covalent inhibitors, interpret
      structure-activity relationships (SARs), translate activity from biochemical
      assays to the cell, and more accurately define selectivity. It is also proposed
      that a physiologically relevant kinact/KI and an (unbound) AUC generated from a
      pharmacokinetic profile reflecting direct exposure of the inhibitor to the target
      protein are two critical determinants of in vivo covalent occupancy. A simple
      equation is presented to define this relationship and improve the interpretation
      of covalent and irreversible kinetics.

PMID- 27703081
TI  - Development of Cell-Defined Lentivirus-Based Microarray for Mammalian Cells.
AB  - Although reverse transfection cell microarray (RTCM) is a powerful tool for
      mammalian cell studies, the technique is not appropriate for cells that are
      difficult to transfect. The lentivirus-infected cell microarray (LICM) technique
      was designed to improve overall efficiency. However, LICM presents new challenges
      because individual lentiviral particles can spread through the cell population,
      leading to cross-contamination. Therefore, we designed a cell-defined lentivirus
      microarray (CDLM) technique using cell-friendly biomaterials that are controlled
      by cell attachment timing. We selected poly-l-lysine (PLL) with Matrigel as the
      best combination of biomaterials for cell-defined culture. We used 2 uL PLL to
      determine by titration the optimum concentration required (0.04% stock, 0.005%
      final concentration). We also determined the optimum concentration of 10 uL of
      lentivirus particles for maximum reverse infection efficiency (1 * 108 infectious
      units [IFU]/mL stock, 62.5% final concentration) and established the best
      combination of components for the lentivirus mixture (10 uL of lentivirus
      particles and 2 uL each of siGLO Red dye, Matrigel, and 0.04% PLL). Finally, we
      validated both the effect of reverse infection in various cell lines and
      lentivirus spot activity in CDLM by storage period. This method provides an
      effective lentivirus-infected cell microarray for large-scale gene function
      studies.

PMID- 27703082
TI  - Fluorescent Parkin Cell-Based Assay Development for the Screening of Drugs
      against Parkinson Disease.
AB  - Parkinson disease (PD) is a prevalent neurodegenerative disease characterized by
      selective degeneration of dopaminergic neurons in the substantia nigra, causing
      tremor and motor impairment. Parkin protein, whose mutants are the cause of
      Parkinson disease type 2 (PARK2), has been mechanistically linked to the
      regulation of apoptosis and the turnover of damaged mitochondria. Several studies
      have implicated aberrant mitochondria as a key contributor to the development of
      PD. In the attempt to discover new drugs, high-content cell-based assays are
      becoming more important to mimic the nature of biological processes and their
      diversifications in diseases and will be essential for lead identification and
      the optimization of therapeutic candidates. We have developed a novel
      fluorescence cell-based assay for high-content screening to find compounds that
      can promote the mitochondrial localization of Parkin without severe mitochondrial
      damage induction. In this work, this model was used to screen a library of 1280
      compounds. After the screening campaign, the positive compounds were chosen for
      further testing, based on the strength of the initial response and lack of
      cytotoxicity. These results indicated that this Parkin cell-based assay is a
      robust (Z' > 0.5) and valid strategy to test potential candidates for preclinical
      studies.

PMID- 27703084
TI  - Coping with stress: mechanics of the expanding leaf.

PMID- 27703083
TI  - Hairless but no longer clueless: understanding glandular trichome development.

PMID- 27703085
TI  - White Matter Microstructure Improves Stroke Risk Prediction in the General
      Population.
AB  - BACKGROUND AND PURPOSE: The presence of subclinical vascular brain disease,
      including white matter lesions and lacunar infarcts, substantially increases the
      risk of clinical stroke. White matter microstructural integrity is considered an
      earlier, potentially better, marker of the total burden of vascular brain
      disease. Its association with risk of stroke, a focal event, remains unknown.
      METHODS: From the population-based Rotterdam Study, 4259 stroke-free participants
      (mean age: 63.6 years, 55.6% women) underwent brain magnetic resonance imaging,
      including diffusion magnetic resonance imaging, between 2006 and 2011. All
      participants were followed up for incident stroke until 2013. Cox proportional
      hazards models were used to associate markers of the microstructure of normal
      appearing white matter with risk of stroke, adjusting for age, sex, white matter
      lesion volume, lacunar infarcts, and additionally for cardiovascular risk
      factors. Finally, we assessed the predictive value of white matter
      microstructural integrity for stroke beyond the Framingham Stroke Risk Profile.
      RESULTS: During 18 476 person-years of follow-up, 58 people experienced a stroke.
      Both lower fractional anisotropy and higher MD increased risk of stroke,
      independent of age, sex, cardiovascular risk factors, white matter lesion volume,
      and lacunar infarcts (hazard ratio per SD increase in: fractional anisotropy:
      0.75 [95% confidence interval, 0.57-0.98] and MD: 1.50 [95% confidence interval,
      1.08-2.09]). MD improved stroke prediction beyond the Framingham Stroke Risk
      Profile (continuous net reclassification improvement: 0.52 [95% confidence
      interval, 0.24-0.81]). CONCLUSIONS: Future stroke is predicted not only by
      prevalent vascular lesions but also by subtle alterations in the microstructure
      of normal-appearing white matter. Inclusion of this effect in risk prediction
      models produces a significant advantage in stroke prediction compared with the
      existing Framingham Stroke Risk Profile.

PMID- 27703086
TI  - Emerging Risk Factors for Recurrent Vascular Events in Patients With Embolic
      Stroke of Undetermined Source.
AB  - BACKGROUND AND PURPOSE: Underlying embolic causes diagnosed by transesophageal
      echocardiography could be implicated in mechanisms of embolic stroke of
      undetermined source. We aimed to explore factors, including underlying embolic
      causes, related to recurrent vascular events in embolic stroke of undetermined
      source. METHODS: Patients who fulfilled the diagnostic criteria for embolic
      stroke of undetermined source and whose potential embolic sources were examined
      by transesophageal echocardiography were included. Recurrent vascular events,
      including ischemic stroke, cardiovascular and peripheral artery diseases, and
      vascular death, were retrospectively analyzed. Cox proportional hazards
      regression analysis was used to explore factors, including clinical
      characteristics, embolic causes on transesophageal echocardiography, and the
      Calcification in the Aortic Arch, Age, Multiple Infarction score (CAM), based on
      the degree of aortic arch calcification on chest radiograph (0-3 points), age
      (>=70 years; 1 point), and multiple infarctions on magnetic resonance imaging
      (multiple infarcts in 1, 2, or >=3 territories of large intracranial arteries, 1,
      2, or 3 points) associated with recurrent vascular events. RESULTS: A total of
      177 patients (age, 64.1+/-14.2 years; 127 men) were enrolled. Thirty-one patients
      had recurrent vascular events (follow-up, 3.5+/-2.7 years; annualized rate, 5.0%
      per person-year). Among embolic causes on transesophageal echocardiography,
      incidence of recurrent vascular events was high in patients with large aortic
      arch plaques (7.5% per person-year). Diabetes mellitus (hazard ratio, 2.56; 95%
      confidence interval, 1.23-5.32; P=0.012) and CAM score grade (hazard ratio, 2.29;
      95% confidence interval, 1.11-4.72; P=0.026) predicted recurrent vascular events.
      CONCLUSIONS: History of diabetes mellitus and the CAM score could be novel risk
      factors for recurrent vascular events in embolic stroke of undetermined source.

PMID- 27703087
TI  - Cerebral Small Vessel Disease Burden Is Increased in Systemic Lupus
      Erythematosus.
AB  - BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) increases stroke risk,
      but the mechanism is uncertain. This study aimed to determine the association
      between SLE and features on neuroimaging of cerebral small vessel disease (SVD),
      a risk factor for stroke. METHODS: Consecutive patients attending a clinic for
      SLE were recruited. All patients underwent brain magnetic resonance imaging; had
      blood samples taken for markers of inflammation, endothelial dysfunction,
      cholesterol, and autoantibodies; and underwent cognitive and psychiatric testing.
      The data were compared with sex- and age-matched healthy controls and patients
      with minor stroke. Features of SVD were measured, a total SVD score calculated,
      and associations sought with vascular risk factors, cognition, SLE activity, and
      disease duration. RESULTS: Fifty-one SLE patients (age: 48.8 years; SD: 14.3
      years) had a greater total SVD score compared with healthy controls (1 versus 0;
      P<0.0001) and stroke patients (1 versus 0; P=0.02). There were higher
      perivascular spaces and deep white matter hyperintensity scores and more
      superficial brain atrophy in SLE patients versus healthy controls. Despite fewer
      vascular risk factors than similarly aged stroke patients, SLE patients had
      similar or more of some SVD features. The total SVD score was not associated with
      SLE activity, cognition, disease duration, or any blood measure. CONCLUSIONS: In
      this data set, SLE patients had a high burden of SVD features on magnetic
      resonance imaging, particularly perivascular spaces. A larger longitudinal study
      is warranted to determine the causes of SVD features in SLE and clinical
      implications.

PMID- 27703088
TI  - Rheumatic Mitral Valve Disease Is Associated With Worse Outcomes in Stroke: A
      Thailand National Database Study.
AB  - BACKGROUND AND PURPOSE: Rheumatic valvular heart disease is associated with the
      increased risk of cerebrovascular events, although there are limited data on the
      prognosis of patients with rheumatic mitral valve disease (RMVD) after stroke.
      METHODS: We examined the association between RMVD and both serious and common
      cardiovascular and noncardiovascular (respiratory and infective) complications in
      a cohort of hospitalized stroke patients based in Thailand. Factors associated
      with in-hospital mortality were also explored. Data were obtained from a National
      Insurance Database. All hospitalized strokes between October 1, 2004, and January
      31, 2013, were included in the current study. Characteristics and outcomes were
      compared for RMVD and non-RMVD patients. Logistic regression, propensity score
      matching, and multivariate models were used to assess study outcomes. RESULTS: In
      total, 594 681 patients (mean [SD] age=64 [14.5] years) with a diagnosis of
      stroke (ischemic=306 154; hemorrhagic=195 392; undetermined=93 135) were included
      in this study, of whom 5461 had RMVD. Results from primary analyses showed that
      after ischemic stroke, and controlling for potential confounding covariates, RMVD
      was associated (P<0.001) with increased odds for cardiac arrest (odds ratio [95%
      confidence interval]=2.13 [1.68-2.70]), shock (2.13 [1.64-2.77]), arrhythmias
      (1.70 [1.21-2.39]), respiratory failure (2.09 [1.87-2.33]), pneumonia (2.00 [1.81
      2.20]), and sepsis (1.39 [1.19-1.63]). In hemorrhagic stroke patients, RMVD was
      associated with increased odds (fully adjusted model) for respiratory failure
      (1.26 [1.01-1.57]), and in patients with undetermined stroke, RMVD was associated
      with increased odds (fully adjusted analyses) for shock (3.00 [1.46-6.14]),
      respiratory failure (2.70 [1.91-3.79]), and pneumonia (2.42 [1.88-3.11]).
      CONCLUSIONS: RMVD is associated with the development of cardiac arrest, shock,
      arrhythmias, respiratory failure, pneumonia, and sepsis after acute stroke.

PMID- 27703089
TI  - Development and Validation of an Automatic Segmentation Algorithm for
      Quantification of Intracerebral Hemorrhage.
AB  - BACKGROUND AND PURPOSE: ABC/2 is still widely accepted for volume estimations in
      spontaneous intracerebral hemorrhage (ICH) despite known limitations, which
      potentially accounts for controversial outcome-study results. The aim of this
      study was to establish and validate an automatic segmentation algorithm, allowing
      for quick and accurate quantification of ICH. METHODS: A segmentation algorithm
      implementing first- and second-order statistics, texture, and threshold features
      was trained on manual segmentations with a random-forest methodology.
      Quantitative data of the algorithm, manual segmentations, and ABC/2 were
      evaluated for agreement in a study sample (n=28) and validated in an independent
      sample not used for algorithm training (n=30). RESULTS: ABC/2 volumes were
      significantly larger compared with either manual or algorithm values, whereas no
      significant differences were found between the latter (P<0.0001; Friedman+Dunn's
      multiple comparison). Algorithm agreement with the manual reference was strong
      (concordance correlation coefficient 0.95 [lower 95% confidence interval 0.91])
      and superior to ABC/2 (concordance correlation coefficient 0.77 [95% confidence
      interval 0.64]). Validation confirmed agreement in an independent sample
      (algorithm concordance correlation coefficient 0.99 [95% confidence interval
      0.98], ABC/2 concordance correlation coefficient 0.82 [95% confidence interval
      0.72]). The algorithm was closer to respective manual segmentations than ABC/2 in
      52/58 cases (89.7%). CONCLUSIONS: An automatic segmentation algorithm for
      volumetric analysis of spontaneous ICH was developed and validated in this study.
      Algorithm measurements showed strong agreement with manual segmentations, whereas
      ABC/2 exhibited its limitations, yielding inaccurate overestimations of ICH
      volume. The refined, yet time-efficient, quantification of ICH by the algorithm
      may facilitate evaluation of clot volume as an outcome predictor and trigger for
      surgical interventions in the clinical setting.

PMID- 27703090
TI  - Response by Ehrlich et al to Letter Regarding Article, "Safety of Computed
      Tomographic Angiography in the Evaluation of Patients With Acute Stroke: A Single
      Center Experience".

PMID- 27703091
TI  - Letter by Wu et al Regarding Article, "Safety of Computed Tomographic Angiography
      in the Evaluation of Patients With Acute Stroke: A Single-Center Experience".

PMID- 27703092
TI  - Survival Outcomes for Combined Modality Therapy for Sinonasal Undifferentiated
      Carcinoma.
AB  - Objective Sinonasal undifferentiated carcinoma is a rare and aggressive
      malignancy of the nasal cavity and paranasal sinuses. Multi-institutional studies
      examining outcomes of combined modality treatment versus other treatment
      modalities have not been performed. The objective of our study was to present
      outcomes for multimodality therapy through use of the National Cancer Database.
      Study Design Retrospective cohort study. Setting National Cancer Database.
      Methods A total of 435 cases of SNUC diagnosed between 2004 and 2012 were
      identified. Kaplan-Meier analyses were performed to find 5-year cumulative
      survival rates. Multivariate Cox regression evaluated overall survival based on
      treatment when adjusting for other prognostic factors (age, primary site, sex,
      race, comorbidity, insurance, and TNM stage). Within the surgery +
      chemoradiotherapy group, survival analysis was also performed to compare outcomes
      for induction and adjuvant chemotherapy. Results The cumulative 5-year survival
      rate was 41.5%, and 36.1% of patients received surgery with chemoradiotherapy. In
      multivariate analysis, surgery + chemoradiotherapy was associated with
      significantly improved overall survival versus surgery + radiotherapy and
      radiotherapy but not significantly different from chemoradiotherapy. Within the
      surgery + chemoradiotherapy group, induction and adjuvant chemotherapy groups did
      not have associated differences in survival. Conclusion Combined modality therapy
      (chemoradiotherapy or surgery + chemoradiotherapy) is associated with improved
      survival outcomes versus other treatment modalities in patients with sinonasal
      undifferentiated carcinoma.

PMID- 27703093
TI  - Prevalence and Surgical Implications of Dural Enhancement at the Porus Acusticus
      in Vestibular Schwannomas.
AB  - OBJECTIVE: Demonstrate the association of radiographic dural enhancement with
      increased tumor adherence at the porus acusticus, which may influence
      completeness of resection and facial nerve outcome. STUDY DESIGN: Case series
      with chart review. SETTING: Academic referral center. SUBJECTS AND METHODS: A
      total of 205 consecutive patients with histopathologically confirmed vestibular
      schwannoma (VS) were evaluated. Patients with tumors exhibiting dural enhancement
      on postgadolinium T1-weighted magnetic resonance imaging were identified and
      compared with matched controls. Completeness of resection, intraoperative
      details, and facial nerve outcomes were analyzed. RESULTS: Excluding strictly
      intracanalicular tumors (n = 32, 16%) and those with NF2 (n = 10, 4.9%), the
      presence of dural enhancement was radiographically confirmed in 16 (9.8%) cases.
      Paired analysis did not reveal significant baseline differences between cases and
      controls. Subtotal resection was performed in 5 (31%) of the 16 patients with
      tumors exhibiting dural enhancement, in contrast to 1 (3%) of the matched
      controls (P = .01). Four (25%) demonstrated increased tumor adherence at the
      porus acusticus intraoperatively, compared with 1 control (3%, P = .04). Long
      term facial nerve function was similar between cases and controls (81% vs 84%
      House-Brackmann I-II function, P = 1.00). CONCLUSION: Dural enhancement is
      present in approximately 10% of extracanalicular VS. Dural enhancement at the
      porus acusticus may represent hypervascularity, dural reaction, or infiltration,
      and portends increased tumor adherence and greater likelihood of subtotal
      resection to preserve facial nerve function. To our knowledge, this is the first
      series that reports the prevalence of this phenomenon in VS and the potential
      surgical implications. Recognition preoperatively may be valuable toward patient
      counseling.

PMID- 27703094
TI  - Racial and Ethnic Disparities in Nasopharyngeal Cancer Survival in the United
      States.
AB  - Objective To determine whether patient race and ethnicity affect nasopharyngeal
      cancer survival. Study Design Retrospective database analysis. Setting National
      Cancer Institute's SEER database (Surveillance, Epidemiology, and End Results),
      1988-2010. Subjects and Methods Nasopharyngeal carcinoma cases were extracted
      according to site codes and histology recode-broad groupings. The cohort of 5427
      patients was used to calculate disease-specific survival in regard to race and
      ethnicity. Extracted data were further analyzed through direct comparisons and
      multivariable Cox regression models controlling for patient, tumor, and treatment
      characteristics. Results Unadjusted survival curves for all nasopharyngeal
      carcinomas considered together showed a statistically significant better disease
      specific survival for the African American race ( P = .02) and Asian ethnicity (
      P = .01) relative to Caucasian patients. The survival advantage for both these
      groups was eliminated after controlling for the age and sex of the patients.
      Conclusion African American and Asian patients with nasopharyngeal cancer have
      better disease-specific survival as compared with Caucasian patients, while
      Hispanic ethnicity has no effect relative to Caucasians. This disparity is
      accounted for by diagnosis at an older age in Caucasian patients but remains
      poorly explained in regard to Hispanic patients.

PMID- 27703095
TI  - Screening for the metabolic syndrome in subjects with migraine.
AB  - Background Metabolic syndrome (MetS) and migraine are known to be associated.
      This study assessed the risk of MetS and its clinical characteristics in migraine
      with aura (MA) and without aura (MO) based on a large-scale cross-sectional
      survey. Methods The study material consisted of 751 participants in the
      Nutrition, Environment and CardioVascular Health (NESCaV) survey. Diagnosis of
      migraine was based on the ef-ID migraine questionnaire and MetS was defined
      according to the Revised-Adult Treatment Panel III criteria. Sociodemographic and
      risk factors were also recorded. Weighted logistic regression was used to assess
      the risk of MetS. Results After adjusting for stratification (gender, age,
      district) and other factors (smoking status, sedentary lifestyle, family history
      of stroke, myocardial infarction and hypertension), MA subjects were at higher
      risk of MetS (OR 3.45; 95% CI: 1.63-7.29) while MO individuals were not, when
      compared to non-migraineurs. When considering MetS components, MA was positively
      associated with low HDL-cholesterol (OR 2.26; 95% CI: 1.08-4.74), hyperglycemia
      (OR 2.77; 95% CI: 1.30-5.88) and abdominal obesity (OR 2.03; 95% CI: 1.07-3.86).
      Conclusion Migraineurs with aura are at higher risk of MetS, suggesting that
      these subjects, already more exposed to stroke, may benefit from a systematic
      screening for the metabolic syndrome.

PMID- 27703096
TI  - Wuling Capsule for Major Depressive Disorder: A Meta-analysis of Randomised
      Controlled Trials.
AB  - INTRODUCTION: In China, Wuling capsule, a traditional Chinese medicine consisting
      of Wuling mycelia of Xylaria nigripes (Kl.) Sacc (a rare type of fungus), is used
      to treat major depressive disorders. A meta-analysis of randomised controlled
      trials was performed to compare the efficacy and safety of Wuling capsule alone
      with Wuling capsule-antidepressant combination in the treatment of major
      depressive disorders. METHODS: Two assessors independently selected studies,
      extracted data, and conducted quality assessment and data synthesis. Standard
      mean difference, risk ratio (RR) +/- 95% confidence interval (CI), the number
      needed to treat, and the number needed to harm were analysed. RESULTS: A total of
      12 randomised controlled trials (880 patients; mean age +/- standard deviation,
      39.7 +/- 12.5 years; male patients, 41%) were identified, including 4 trials with
      Wuling capsule alone (n = 340) and 8 with Wuling capsule-antidepressant
      (sertraline, mianserin, mirtazapine, and paroxetine) combination (n = 540). The
      mean length of trial was 5.7 +/- 1.3 weeks. Meta-analysis of symptomatic
      improvement at last-observation endpoint and study-defined response and remission
      revealed no significant differences between the Wuling capsule alone and
      antidepressant monotherapy. The Wuling capsule-antidepressant cotreatment was
      superior to antidepressant monotherapy in symptomatic improvement at last
      observation endpoint (standard mean difference: -0.46, p = 0.001) as well as
      study-defined response (68.4% vs. 56.0%, RR = 1.23; p = 0.03) and remission
      (46.5% vs. 34.5%, RR = 1.35; p = 0.05). Wuling capsule was associated with fewer
      adverse drug reactions than antidepressant monotherapy. CONCLUSIONS: Adjunctive
      Wuling capsule may augment the effects of antidepressants and may be associated
      with fewer adverse drug reactions. More large-scale and rigorously designed
      randomised controlled trials with large sample size are warranted to clarify the
      effectiveness of Wuling capsule for major depressive disorders.

PMID- 27703097
TI  - Socio-demographic and Clinical Characteristics of Patients who Attempt Suicide: A
      Hospital-based Study from Eastern India.
AB  - INTRODUCTION: Suicide has become an important public health concern with a high
      number of deaths and increasing number of attempted suicides every year. There
      are multiple factors that underlie a suicide attempt. Although mental illness and
      severe stress have long been known to be associated with suicide, socio
      demographic and clinical characteristics of those attempting suicide can also
      provide indications of suicidal intent. The present study aimed to explore the
      socio-demographic and clinical characteristics of patients in Kolkata, India who
      attempted suicide. METHODS: Consecutive patients (n = 100) with failed suicide
      attempt who were referred to the psychiatry department of 2 multispecialty
      hospitals in Kolkata were included in the study. Their socio-demographic details
      and clinical characteristics were recorded. Suicidal intent and depressive
      symptoms were assessed and psychosocial risk factors were identified following
      detailed clinical interview. RESULTS: Suicide attempt was more frequent among
      younger female patients. Reaction to stress was the most common risk factor. The
      majority of attempts were impulsive in nature rather than planned. CONCLUSION:
      Young adults under stress are more vulnerable. Early identification of such
      individuals and psychosocial support to prevent suicidal ideation is vital.

PMID- 27703098
TI  - Cognitive Dysfunction and Associated Behaviour Problems in Postpartum Women: A
      Study from North India.
AB  - OBJECTIVES: During and after childbirth women undergo tremendous psychological
      and biological changes. These biological changes, along with the stress of
      assuming the new role of mother, make postpartum women vulnerable to various
      psychiatric disorders including cognitive dysfunction, depression, and anxiety.
      Such problems are under-reported as they are difficult to identify, especially by
      caregivers who are more focused on the newborn. The present study aimed to
      evaluate the prevalence of behaviour problems and cognitive dysfunction during
      the postpartum period. METHODS: A cross-sectional study was carried out at the
      Department of Obstetrics and Gynaecology, Jawahar Lal Nehru Medical College,
      Ajmer, India. The study sample included 200 consecutive women who came for their
      first follow-up after childbirth, and 100 healthy and non-pregnant women who
      served as controls. Cognitive function was assessed using the Standard Mini
      Mental State Examination Scale (SMMSE), Brief Cognitive Rating Scale (BCRS), and
      Trail Making Test Part B (TMT-B). 21-Item Depression Anxiety and Stress Scale was
      administered to assess depressive and anxiety symptoms. RESULTS: Postpartum women
      scored poorly on SMMSE, BCRS, and TMT-B compared with non-pregnant women (p <
      0.001), whereas subscores of depression, anxiety, and stress were significantly
      higher (p < 0.001). CONCLUSIONS: Women had significantly more cognitive deficits
      during the postpartum period than their non-pregnant counterparts. The former
      also had a higher prevalence of depression, anxiety, and stress.

PMID- 27703099
TI  - Antiepileptic-induced Psychosis as a Possible Predictor of Post-temporal
      Lobectomy Alternative Psychosis.
AB  - We present a patient with topiramate-induced psychosis who developed alternative
      psychosis following temporal lobectomy. The number of surgical candidates for
      temporal lobectomy is increasing as is the frequency of psychiatric co
      morbidities. Preoperative planning should take account of these psychiatric co
      morbidities. In particular, precautions should be taken when antiepileptic drug
      induced psychosis occurs, as this could predict the occurrence of alternative
      psychosis following lobectomy.

PMID- 27703100
TI  - Null Hypothesis Testing (I) - 5% Significance Level.

PMID- 27703101
TI  - [Multiple Dopamine Signals and Their Contributions to Reinforcement Learning].
AB  - Midbrain dopamine neurons are activated by reward and sensory cue that predicts
      reward. Their responses resemble reward prediction error that indicates the
      discrepancy between obtained and expected reward values, which has been thought
      to play an important role as a teaching signal in reinforcement learning. Indeed,
      pharmacological blockade of dopamine transmission interferes with reinforcement
      learning. Recent studies reported, however, that not all dopamine neurons
      transmit the reward-related signal. They found that a subset of dopamine neurons
      transmits signals related to non-rewarding, salient experiences such as aversive
      stimulations and cognitively demanding events. How these signals contribute to
      animal behavior is not yet well understood. This article reviews recent findings
      on dopamine signals related to rewarding and non-rewarding experiences, and
      discusses their contributions to reinforcement learning.

PMID- 27703102
TI  - [Drug Dependence and Toxicity of Law-Evading Drugs: Their Mechanisms Explored
      from Basic Research].
AB  - The number of law-evading chemical substances that pose serious health risks to
      humans is increasing worldwide, including Japan and the Western world, and their
      abuse is becoming a serious social problem. Analysis of the chemical substances
      in these herbal products revealed the presence of synthetic cannabinoids. This
      review summarizes the pharmacological actions and dangers of chemical substances
      contained in law-evading herbal products by focusing on synthetic cannabinoids as
      a group of chemical substances contained in these products. We established a
      psychic-dependence liability and cytotoxicity screening system for synthetic
      cannabinoids by using animals and cell cultures. In a place-conditioning study,
      the synthetic cannabinoids produced a significant conditioned-place preference.
      The rewarding effects of synthetic cannabinoids were completely suppressed by a
      cannabinoid CB1 receptor antagonist. Administration of synthetic cannabinoids to
      primary striatal culture caused cell death in a dose-dependent manner. Our
      findings show that the CB1 receptor might be involved in the expression of
      synthetic cannabinoid-induced rewarding effect. These behavioral data indicate
      that synthetic cannabinoids have a psychic-dependence liability. Furthermore, our
      data from primary striatal culture indicate that synthetic cannabinoids have
      strong neurotoxicity. These behavioral and neurochemical data indicate that
      synthetic cannabinoids might have strong adverse effects and a psychic-dependence
      liability.

PMID- 27703103
TI  - [The Concept and Treatment of Internet Addiction].
AB  - The Internet now plays a very important role in our lives. However, for some
      people, Internet use can lead to a state that appears to meet the DSM definition
      for a mental disorder. In this review, we briefly discuss definition, symptoms,
      risk factors, prevalence, comorbidities, and personality traits of people who are
      susceptible to becoming addicts. In the second section of the article, various
      types of Internet addiction are discussed, focusing mainly on Internet Gaming
      Disorder and social networking survices (SNS) addiction. Regarding Internet
      Gaming Disorder, we discuss various types of the newly emerged Massive
      Multiplayer Online Games (MMO), as well as theories about why people become
      addicted to them. We do the same for the SNS Addiction for sites like Facebook
      and LINE; again, different types, as well as theories about why some people
      become addicts to such sites are discussed. Finally, preventive measures are
      introduced, focusing on a number of commonly used treatment methods, perticulary
      cognitive behavioral therapy and family therapy.

PMID- 27703104
TI  - [Ethical, Legal, and Social Issues (ELSI) in Gambling Disorder and Its
      Treatment].
AB  - Recently, the Ministry of Health, Labor and Welfare estimated the prevalence rate
      of gambling disorder to be 4.8 percent of the population. This rate is
      outstandingly higher than other countries with prevalence rates between 0.25 and
      2.0 percent. It is also estimated that no fewer than 5 million Japanese suffer
      from the disease. In the last two years, 100 new patients visited the author's
      clinic. On an average, they started gambling at the age of 19.7 years, and
      incurring debt at the age of 25.8 years. They first visited the clinic at an
      average age of 38.2 years, and the average amount they had spent on gambling up
      to that point was 13 million yen. Twenty percent of them had taken some legal
      measures to reduce their burden from debts before seeking treatment. Sixty
      percent of pathological gamblers exclusively played pachinko and slot machine
      games. Patients who did not play on such machines accounted for no less than 2
      percent of cases. This is not surprising, considering the fact that Japan has
      nearly 4.6 million pachinko and slot machines, which account for two thirds of
      the total electric gaming machines in the world. Japanese legislation does not
      regard pachinko and slot machines as gambling, but merely as gaming. Therefore,
      pachinko companies have no restrictions as such to promote their market. They can
      advertise freely in newspapers and TV commercials. Pachinko halls are filled with
      lighting, sounds, and visual effects to stimulate and excite gamblers. The
      harmful effects of gambling disorder include depression, loss of employment and
      friends, marital discord, fraud, embezzlement, theft in the family, and theft
      from non-family members. The most helpful therapy involves attending self-help
      group sessions at least once a week. One of the best-known self-help groups is
      Gamblers Anonymous (GA); there are 162 GA groups in Japan. The author believes
      there should be one GA group for every city across the nation. Unfortunately,
      psychiatrists, who should be taking the lead in providing diagnosis and
      treatment, are showing little interest in gambling problems. Unless all
      psychiatrists develop the ability to deal with the disease effectively, there is
      little hope for patients and families to see a light at the end of the tunnel. It
      is also time for the administration to implement necessary measures instead of
      averting its eyes from the harsh reality and promoting publicly managed gambling.
      Considering the miserable situation, the administration should not lift its ban
      on the casino industry.

PMID- 27703105
TI  - [The Concept and Treatment of Kleptomania].
AB  - Research on kleptomania has lagged behind that of other mental disorders, and
      very few clinicians specialize in treating such patients. Futhermore, the
      descriptive outline of kleptomania in the DSM-5 is vague. In 2008, we started a
      registration system for patients suffering from habitual theft, which has
      recorded 1430 cases since its inauguration. In this report, we explain the
      concept of kleptomania and describe our clinical experience in the treatment of
      patients suffering from this mental disorder. The most frequent complication of
      kleptomania was found to be eating disorder (especially bulimia). Although many
      factors contribute to the close relationship between these two mental disorders,
      the theory of "saving money on food expenses" as the motive for thefts committed
      by eating disorder patients, oversimplifies a complicated matter, and is
      inadequate as an explanation of the mechanism of this relationship. Medical
      treatment for kleptomania presently comprises counseling (individual
      psychotherapy), cognitive behavioral therapy, family therapy, group
      psychotherapy, psychodrama, and self-help groups, among others. In our addiction
      treatment approach, we have developed and implemented a program wherein recovered
      (recovering) patients share their personal experiences with newcomers and
      beginners, as well as their family members. We strongly encourage patients with
      kleptomania to participate in self-help groups.

PMID- 27703106
TI  - [Recovery from Sexual Addiction].
AB  - Addiction is a disease that can cause an individual to lose his or her life.
      However, addiction can be considered a form of self medication or survival skill.
      If affected individuals attend a mutual aid group, individuals with such
      addiction can share their common experiences and they are willing to will grow
      along spiritual lines.

PMID- 27703107
TI  - [The Prion-like Mechanism in Neurodegenerative Diseases-Current Studies and
      Future Prospects].
AB  - Intracellular abnormal protein deposits, such as tau, alpha-synuclein and TDP-43,
      are the hallmark of many neurodegenerative diseases, and the distributions of
      these pathological proteins are closely correlated with disease symptoms and
      progression. A growing body of evidence strongly suggests that these abnormal
      proteins have prion-like properties: they convert normal proteins into abnormal
      forms, self-propagate through neuronal networks, and then spread in the brain.
      This prion-like propagation of abnormal proteins may account for the diversity,
      selective degeneration and disease progression seen in neurodegenerative
      diseases, although the molecular mechanism remains uncertain the molecular
      details of this mechanism. This review describes recent studies on prion-like
      properties of abnormal proteins in vitro, in cells and in animal experimental
      models.

PMID- 27703108
TI  - [The Function of REM Sleep: Implications from Transgenic Mouse Models].
AB  - Our sleep is composed of rapid eye movement (REM) sleep and non-REM (NREM) sleep.
      REM sleep is the major source of dreams, whereas synchronous cortical
      oscillations, called slow waves, are observed during NREM sleep. Both stages are
      unique to certain vertebrate species, and therefore, REM and NREM sleep are
      thought to be involved in higher-order brain functions. While several studies
      have revealed the importance of NREM sleep in growth hormone secretion, memory
      consolidation and brain metabolite clearance, the functions of REM sleep are
      currently almost totally unknown. REM sleep functions cannot be easily indicated
      from classical REM sleep deprivation experiments, where animals are forced to
      wake up whenever they enter REM sleep, because such experiments produce extreme
      stress due to the stimuli and because REM sleep is under strong homeostatic
      regulation. To overcome these issues, we developed a novel transgenic mouse model
      in which REM sleep can be manipulated. Using these mice, we found that REM sleep
      enhances slow wave activity during the subsequent NREM sleep. Slow wave activity
      is known to contribute to memory consolidation and synaptic plasticity. Thus, REM
      sleep might be involved in higher-order brain functions through its role in
      enhancing slow wave activity.

PMID- 27703109
TI  - [Clinical Implications and Appropriate Use of Amyloid Imaging with florbetapir
      (<sup>18</sup>F) in Diagnosis of Patients with Alzheimer Disease].
AB  - florbetapir (<sup>18</sup>F) is a radiolabeled compound that can be used to
      visualize amyloid-beta (Abeta) plaques in the brains of patients with cognitive
      dysfunction, who are suspected of having Alzheimer disease (AD). Knowing the
      status of Abeta accumulation in the brain is beneficial to selecting therapeutic
      strategies or to planning of laboratory examinations, hence amyloid PET imaging
      is expected to be utilized more often in a clinical setting. Based on the results
      of a clinical study of florbetapir (<sup>18</sup>F), this review discusses the
      usefulness and clinical significance of amyloid PET imaging, and its appropriate
      use in Japan. (Received Octover 7, 2015; Accepted February 15, 2016; Published
      October 1, 2016).

PMID- 27703110
TI  - [Isolated Severe Dysphagia Associated with Medial Medullary Infarction: A Case
      Report and Review of the Literature].
AB  - A 59-year-old man developed a sudden onset of vertigo and nausea, and after a few
      hours, he could not swallow at all. On admission, neurological examination
      revealed severe dysphagia associated with other transient and mild neurological
      deficits, including left facial paresis, and hypesthesia in the right side of his
      body. MRI with diffusion weighted imaging showed a hyperintense signal lesion at
      the left rostral medial region of the medulla, prompting the diagnosis of an
      acute medial medullary infarction. His facial paresis and hypesthesia disappeared
      within 2 weeks. Despite lacking motor paralysis in the tongue, soft palate, and
      pharyngeal muscle, the patient had severe and prolonged dysphagia. It is
      speculated that the lesion in this patient is located at the central pattern
      generator (CPG), which is thought to be the human swallowing center. (Received
      April 1, 2016; Accepted June 1, 2016; Published October 1, 2016).

PMID- 27703112
TI  - Symptomatic Improvement of Gastroparesis with Granisetron Transdermal System.

PMID- 27703111
TI  - [Long Term Survival 66-year-old Female Case with Metamorphopsia as an Initial
      Complaint of Sporadic Creutzfeldt-Jakob Disease].

PMID- 27703113
TI  - Irritable Inflammatory Bowel Syndrome as a Distinct Disease Entity.

PMID- 27703115
TI  - Nav1.7 and Nav1.8: Diabetes-induced Changes in Primary Sensory Neurons in Rats.

PMID- 27703114
TI  - Sex and Gender Differences in Gastroesophageal Reflux Disease.
AB  - It is important to understand sex and gender-related differences in
      gastroesophageal reflux disease (GERD) because gender-related biologic factors
      might lead to better prevention and therapy. Non-erosive reflux disease (NERD)
      affects more women than men. GERD symptoms are more frequent in patients with
      NERD than in those with reflux esophagitis. However, men suffer pathologic
      diseases such as reflux esophagitis, Barrett's esophagus (BE), and esophageal
      adenocarcinoma (EAC) more frequently than women. The prevalence of reflux
      esophagitis is significantly increased with age in women, especially after their
      50s. The mean age of EAC incidence in women is higher than in men, suggesting a
      role of estrogen in delaying the onset of BE and EAC. In a chronic rat reflux
      esophagitis model, nitric oxide was found to be an aggravating factor of
      esophageal injury in a male-predominant way. In addition, the expression of
      esophageal occludin, a tight junction protein that plays an important role in the
      esophageal defense mechanism, was up-regulated in women. This explains the male
      predominance of reflux esophagitis and delayed incidence of BE or EAC in women.
      Moreover, the symptoms such as heartburn, regurgitation, and extra-esophageal
      symptoms have been more frequently reported by women than by men, suggesting that
      sex and gender play a role in symptom perception. Differential sensitivity with
      augmented symptoms in women might have diagnostic and therapeutic influence.
      Furthermore, recent studies have suggested that hormone replacement therapy has a
      protective effect against esophageal cancer. However, an anti-inflammatory role
      of estrogen remains compelling, which means further study is necessary in this
      area.

PMID- 27703116
TI  - A new high-pressure strontium germanate, SrGe2O5.
AB  - The Sr-Ge-O system has an earth-scientific importance as a potentially good low
      pressure analog of the Ca-Si-O system, one of the major components in the
      constituent minerals of the Earth's crust and mantle. However, it is one of the
      germanate systems that has not yet been fully examined in the phase relations and
      structural properties. The recent findings that the SrGeO3 high-pressure
      perovskite phase is the first Ge-based transparent electronic conductor make the
      Sr-Ge-O system interesting in the field of materials science. In the present
      study, we have revealed the existence of a new high-pressure strontium germanate,
      SrGe2O5. Single crystals of this compound crystallized as a co-existent phase
      with SrGeO3 perovskite single crystals in the sample recovered in the compression
      experiment of SrGeO3 pseudowollastonite conducted at 6 GPa and 1223 K. The
      crystal structure consists of germanium-oxygen framework layers stacked along
      [001], with Sr atoms located at the 12-coordinated cuboctahedral site; the layers
      are formed by the corner linkages between GeO6 octahedra and between GeO6
      octahedra and GeO4 tetrahedra. The present SrGe2O5 is thus isostructural with the
      high-pressure phases of SrSi2O5 and BaGe2O5. Comparison of these three compounds
      leads to the conclusion that the structural responses of the GeO6 and GeO4
      polyhedra to cation substitution at the Sr site are much less than that of the
      SrO12 cuboctahedron to cation substitution at the Ge sites. Such a difference in
      the structural response is closely related to the bonding nature.

PMID- 27703117
TI  - The hydrogen-bonded complex bis(tert-butylammonium) 2,6-dichlorophenolate 2,4
      dichlorophenol-2,4-dichlorophenolate tetrahydrofuran disolvate containing a
      chiral R53(10) hydrogen-bonded ring as a supramolecular synthon.
AB  - A fixed hydrogen-bonding motif with a high probability of occurring when
      appropriate functional groups are involved is described as a 'supramolecular
      hydrogen-bonding synthon'. The identification of these synthons may enable the
      prediction of accurate crystal structures. The rare chiral hydrogen-bonding motif
      R53(10) was observed previously in a cocrystal of 2,4,6-trichlorophenol, 2,4
      dichlorophenol and dicyclohexylamine. In the title solvated salt,
      2C4H12N+.C6H3Cl2O-.(C6H3Cl2O-.C6H4Cl2O).2C4H8O, five components, namely two tert
      butylammonium cations, one 2,4-dichlorophenol molecule, one 2,4-dichlorophenolate
      anion and one 2,6-dichlorophenolate anion, are bound by N-H...O and O-H...O
      hydrogen bonds to form a hydrogen-bonded ring, with the graph-set motif R53(10),
      which is further associated with two pendant tetrahydrofuran molecules by N-H...O
      hydrogen bonds. The hydrogen-bonded ring has internal symmetry, with a twofold
      axis running through the centre of the 2,6-dichlorophenolate anion, and is
      isostructural with a previous and related structure formed from 2,4
      dichlorophenol, dicyclohexylamine and 2,4,6-trichlorophenol. In the title
      crystal, helical columns are built by the alignment and twisting of the chiral
      hydrogen-bonded rings, along and across the c axis, and successive pairs of rings
      are associated with each other through C-H...pi interactions. Neighbouring
      helical columns are inversely related and, therefore, no chirality is sustained,
      in contrast to the previous case.

PMID- 27703118
TI  - Two new two-dimensional coordination polymers based on isophthalate and a
      flexible N-donor ligand containing benzimidazole and pyridine rings: synthesis,
      crystal structures and a solid-state UV-Vis study.
AB  - In coordination chemistry and crystal engineering, many factors influence the
      construction of coordination polymers and the final frameworks depend greatly on
      the organic ligands used. N-Donor ligands with diverse coordination modes and
      conformations have been employed to assemble metal-organic frameworks. Carboxylic
      acid ligands can deprotonate completely or partially when bonding to metal ions
      and can also act as donors or acceptors of hydrogen bonds and are thus good
      candidates for the construction of supramolecular architectures. Two new
      transition metal complexes, namely poly[diaqua(MU4-1,4-bis{[1-(pyridin-3
      ylmethyl)-1H-benz[d]imidazol-2-yl]methoxy}benzene)bis(MU2
      isophthalato)dicobalt(II)], [Co(C8H4O4)(C34H28N6O2)0.5(H2O)]n, (1), and
      poly[diaqua(MU4-1,4-bis{[1-(pyridin-3-ylmethyl)-1H-benz[d]imidazol-2
      yl]methoxy}benzene)bis(MU2-isophthalato)dicadmium(II)],
      [Cd(C8H4O4)(C34H28N6O2)0.5(H2O)]n, have been constructed using a symmetric N
      donor ligand and a carboxylate ligand under hydrothermal conditions. X-ray
      crystallographic studies reveal that complexes (1) and (2) are isostructural,
      both of them exhibiting three-dimensional supramolecular architectures built by
      hydrogen bonds in which the coordinated water molecules serve as donors, while
      the O atoms of the carboxylate groups act as acceptors. Furthermore, (1) and (2)
      have been characterized by elemental, IR spectroscopic, powder X-ray diffraction
      (PXRD) and thermogravimetric analyses. The UV-Vis absorption spectrum of complex
      (1) has also been investigated.

PMID- 27703119
TI  - The tropolone-isobutylamine complex: a hydrogen-bonded troponoid without dominant
      pi-pi interactions.
AB  - Tropolone long has served as a model system for unraveling the ubiquitous
      phenomena of proton transfer and hydrogen bonding. This molecule, which
      juxtaposes ketonic, hydroxylic, and aromatic functionalities in a framework of
      minimal complexity, also has provided a versatile platform for investigating the
      synergism among competing intermolecular forces, including those generated by
      hydrogen bonding and aryl coupling. Small members of the troponoid family
      typically produce crystals that are stabilized strongly by pervasive pi-pi, C
      H...pi, or ion-pi interactions. The organic salt (TrOH.iBA) formed by a facile
      proton-transfer reaction between tropolone (TrOH) and isobutylamine (iBA), namely
      isobutylammonium 7-oxocyclohepta-1,3,5-trien-1-olate, C4H12N+.C7H5O2-, has been
      investigated by X-ray crystallography, with complementary quantum-chemical and
      statistical-database analyses serving to elucidate the nature of attendant
      intermolecular interactions and their synergistic effects upon lattice-packing
      phenomena. The crystal structure deduced from low-temperature diffraction
      measurements displays extensive hydrogen-bonding networks, yet shows little
      evidence of the aryl forces (viz. pi-pi, C-H...pi, and ion-pi interactions) that
      typically dominate this class of compounds. Density functional calculations
      performed with and without the imposition of periodic boundary conditions (the
      latter entailing isolated subunits) documented the specificity and directionality
      of noncovalent interactions occurring between the proton-donating and proton
      accepting sites of TrOH and iBA, as well as the absence of aromatic coupling
      mediated by the seven-membered ring of TrOH. A statistical comparison of the
      structural parameters extracted for key hydrogen-bond linkages to those reported
      for 44 previously known crystals that support similar binding motifs revealed
      TrOH.iBA to possess the shortest donor-acceptor distances of any troponoid-based
      complex, combined with unambiguous signatures of enhanced proton-delocalization
      processes that putatively stabilize the corresponding crystalline lattice and
      facilitate its surprisingly rapid formation under ambient conditions.

PMID- 27703120
TI  - Crystal structure and hydrogen bonding in the hydrated cocrystalline salt
      tryptaminium-3,5-dinitrobenzoate-quinoline-water (3/3/2/2).
AB  - The study of ternary systems is interesting because it introduces the concept of
      molecular preference/competition into the system where one molecule may be
      displaced because the association between the other two is significantly
      stronger. Current definitions of a tertiary system indicate that solvent
      molecules are excluded from the molecule count of the system and some of the
      latest definitions state that any molecule that is not a solid in the parent form
      at room temperature should also be excluded from the molecule count. In the
      structure of the quinoline adduct hydrate of tryptaminium 3,5-dinitrobenzoate,
      3C10H13N2+.3C7H3N2O6-.2C9H7N.2H2O, the asymmetric unit comprises multiple cation
      and anion species which are conformationally similar among each type set. In the
      crystal, a one-dimensional hydrogen-bonded supramolecular structure is generated
      through extensive intra- and inter-unit aminium N-H...O and N-H...N, and water O
      H...O hydrogen bonds. Within the central-core hydrogen-bonding associations,
      conjoined cyclic R44(10), R53(10) and R44(12) motifs are generated. The unit is
      expanded into a one-dimensional column-like polymer extending along [010].
      Present also in the crystal packing of the structure are a total of 19 pi-pi
      interactions involving both cation, anion and quinoline species [ring-centroid
      separation range = 3.395 (3)-3.797 (3) A], as well as a number of weak C-H...O
      hydrogen-bonding associations. The presence of the two water molecules in the
      crystal structure is considered to be the principal causative factor in the low
      symmetry of the asymmetric unit.

PMID- 27703121
TI  - The antitumour drug 7-ethyl-10-hydroxycamptothecin monohydrate and its solid
      state hydrolysis mechanism on heating.
AB  - 7-Ethyl-10-hydroxycamptothecin [systematic name: (4S)-4,11-diethyl-4,9-dihydroxy
      1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, SN-38] is an
      antitumour drug which exerts activity through the inhibition of topoisomerase I.
      The crystal structure of SN-38 as the monohydrate, C22H20N2O5.H2O, reveals that
      it is a monoclinic crystal, with one SN-38 molecule and one water molecule in the
      asymmetric unit. When the crystal is heated to 473 K, approximately 30% of SN-38
      is hydrolyzed at its lactone ring, resulting in the formation of the inactive
      carboxylate form. The molecular arrangement around the water molecule and the
      lactone ring of SN-38 in the crystal structure suggests that SN-38 is hydrolyzed
      by the water molecule at (x, y, z) nucleophilically attacking the carbonyl C atom
      of the lactone ring at (x - 1, y, z - 1). Hydrogen bonding around the water
      molecules and the lactone ring appears to promote this hydrolysis reaction: two
      carbonyl O atoms, which are hydrogen bonded as hydrogen-bond acceptors to the
      water molecule at (x, y, z), might enhance the nucleophilicity of this water
      molecule, while the water molecule at (-x, y + 1/2, -z), which is hydrogen bonded
      as a hydrogen-bond donor to the carbonyl O atom at (x - 1, y, z - 1), might
      enhance the electrophilicity of the carbonyl C atom.

PMID- 27703122
TI  - Cocrystals of 1,4-diethynylbenzene with 1,3-diacetylbenzene and benzene-1,4
      dicarbaldehyde exhibiting strong nonconventional alkyne-carbonyl C-H...O hydrogen
      bonds between the components.
AB  - Weak interactions between organic molecules are important in solid-state
      structures where the sum of the weaker interactions support the overall three
      dimensional crystal structure. The sp-C-H...N hydrogen-bonding interaction is
      strong enough to promote the deliberate cocrystallization of a series of diynes
      with a series of dipyridines. It is also possible that a similar series of
      cocrystals could be formed between molecules containing a terminal alkyne and
      molecules which contain carbonyl O atoms as the potential hydrogen-bond acceptor.
      I now report the crystal structure of two cocrystals that support this
      hypothesis. The 1:1 cocrystal of 1,4-diethynylbenzene with 1,3-diacetylbenzene,
      C10H6.C10H10O2, (1), and the 1:1 cocrystal of 1,4-diethynylbenzene with benzene
      1,4-dicarbaldehyde, C10H6.C8H6O2, (2), are presented. In both cocrystals, a
      strong nonconventional ethynyl-carbonyl sp-C-H...O hydrogen bond is observed
      between the components. In cocrystal (1), the C-H...O hydrogen-bond angle is
      171.8 (16) degrees  and the H...O and C...O hydrogen-bond distances are 2.200
      (19) and 3.139 (2) A, respectively. In cocrystal (2), the C-H...O hydrogen-bond
      angle is 172.5 (16) degrees  and the H...O and C...O hydrogen-bond distances are
      2.25 (2) and 3.203 (2) A, respectively.

PMID- 27703123
TI  - Acetic anhydride at 100 K: the first crystal structure determination.
AB  - Acetic anhydride (ethanoic anhydride), (CH3CO)2O, is a widely used acetylation
      reagent in organic synthesis. The crystal and molecular structure, as determined
      by single-crystal X-ray analysis at 100 K, is reported for the first time. A
      crystal of the title compound (m.p. 200 K) suitable for X-ray diffraction was
      grown from the melt at low temperature. The title compound crystallizes in the
      orthorhombic space group Pbcn, with Z = 4. In the crystal, the molecule adopts an
      exact C2-symmetric conformation about a crystallographic twofold axis. The
      molecules are densely packed. Two of the methyl H atoms form short intermolecular
      contacts to a neighbouring carbonyl O atom, which can be viewed as weak hydrogen
      bonds.

PMID- 27703124
TI  - Crystallization experiments with the dinuclear chelate ring complex di-MU
      chlorido-bis[(eta2-2-allyl-4-methoxy-5-{[(propan-2-yloxy)carbonyl]methoxy}phenyl
      kappaC1)platinum(II)].
AB  - Crystallization experiments with the dinuclear chelate ring complex di-MU
      chlorido-bis[(eta2-2-allyl-4-methoxy-5-{[(propan-2-yloxy)carbonyl]methoxy}phenyl
      kappaC1)platinum(II)], [Pt2(C15H19O4)2Cl2], containing a derivative of the
      natural compound eugenol as ligand, have been performed. Using five different
      sets of crystallization conditions resulted in four different complexes which can
      be further used as starting compounds for the synthesis of Pt complexes with
      promising anticancer activities. In the case of vapour diffusion with the binary
      chloroform-diethyl ether or methylene chloride-diethyl ether systems, no change
      of the molecular structure was observed. Using evaporation from acetonitrile (at
      room temperature), dimethylformamide (DMF, at 313 K) or dimethyl sulfoxide (DMSO,
      at 313 K), however, resulted in the displacement of a chloride ligand by the
      solvent, giving, respectively, the mononuclear complexes (acetonitrile
      kappaN)(eta2-2-allyl-4-methoxy-5-{[(propan-2-yloxy)carbonyl]methoxy}phenyl
      kappaC1)chloridoplatinum(II) monohydrate, [Pt(C15H19O4)Cl(CH3CN)].H2O, (eta2-2
      allyl-4-methoxy-5-{[(propan-2-yloxy)carbonyl]methoxy}phenyl
      kappaC1)chlorido(dimethylformamide-kappaO)platinum(II), [Pt(C15H19O4)Cl(C2H7NO)],
      and (eta2-2-allyl-4-methoxy-5-{[(propan-2-yloxy)carbonyl]methoxy}phenyl
      kappaC1)chlorido(dimethyl sulfoxide-kappaS)platinum(II), determined as the
      analogue {eta2-2-allyl-4-methoxy-5-[(ethoxycarbonyl)methoxy]phenyl
      kappaC1}chlorido(dimethyl sulfoxide-kappaS)platinum(II),
      [Pt(C14H17O4)Cl(C2H6OS)]. The crystal structures confirm that acetonitrile
      interacts with the PtII atom via its N atom, while for DMSO, the S atom is the
      coordinating atom. For the replacement, the longest of the two Pt-Cl bonds is
      cleaved, leading to a cis position of the solvent ligand with respect to the
      allyl group. The crystal packing of the complexes is characterized by dimer
      formation via C-H...O and C-H...pi interactions, but no pi-pi interactions are
      observed despite the presence of the aromatic ring.

PMID- 27703126
TI  - Treatment outcomes after adjuvant radiotherapy following surgery for patients
      with stage I endometrial cancer.
AB  - PURPOSE: The purpose of this study is to evaluate the treatment outcomes of
      adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per
      fraction and/or external beam radiotherapy (EBRT) following surgery for patients
      with stage I endometrial carcinoma. MATERIALS AND METHODS: The subjects were 43
      patients with the International Federation of Gynecology and Obstetrics (FIGO)
      stage I endometrial cancer who underwent adjuvant radiotherapy following surgery
      between March 2000 and April 2014. Of these, 25 received postoperative VB alone,
      while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated
      with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0-50.4 Gy) and the VB
      dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from
      the cylinder surface and delivered twice per week. RESULTS: The median follow-up
      period for all patients was 57 months (range, 9 to 188 months). Five-year disease
      free survival (DFS) and overall survival (OS) for all patients were 92.5% and
      95.3%, respectively. Adjuvant radiotherapy was performed according to risk
      factors and stage IB, grade 3 and lymphovascular invasion were observed more
      frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and
      96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4%
      and 96%, respectively (p = 0.38). There was no locoregional recurrence in any
      patient. Two patients who received EBRT and 1 patient who received VB alone
      developed distant metastatic disease. Two patients who received EBRT had severe
      complications, one each of grade 3 gastrointestinal complication and pelvic bone
      insufficiency fracture. CONCLUSION: Adjuvant radiotherapy achieved high DFS and
      OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose
      per fraction) may be a viable option for selected patients with early-stage
      endometrial cancer following surgery.

PMID- 27703127
TI  - Age-period-cohort analysis of hepatitis A incidence rates in Korea from 2002 to
      2012.
AB  - OBJECTIVES: This study aimed to evaluate the epidemiology of hepatitis A in Korea
      from 2002 to 2012 using age-period-cohort analyses. METHODS: We used claims data
      from the Korean National Health Insurance Corporation for the entire population.
      Census data from 2010 were used as the standard population. The incidence of
      hepatitis A was assumed to have a Poisson distribution, and the models and
      effects were evaluated using the intrinsic estimator method, the likelihood
      ratio, and the Akaike information criterion. RESULTS: The incidence of hepatitis
      A gradually increased until 2007 (from 17.55 to 35.72 per 100,000 population) and
      peaked in 2009 (177.47 per 100,000 population). The highest incidence was
      observed among 27-29-year-old individuals when we omitted data from 2005 to 2007.
      From 2005 to 2007, the peak incidence was observed among 24-26-year-old
      individuals, followed by 27-29-year-olds. The best model fits were observed when
      the age-period-cohort variables were all considered at the same time for males,
      females, and the whole population. CONCLUSIONS: The incidence of hepatitis A
      exhibited significant age-period-cohort effects; its incidence peaked in 2009 and
      was especially high among Koreans 20-39 years of age. These epidemiological
      patterns may help predict when high incidence rates of hepatitis A may occur in
      developing countries during their socioeconomic development.

PMID- 27703130
TI  - Use of Lysozyme as a Feed Additive on In vitro Rumen Fermentation and Methane
      Emission.
AB  - This study was conducted to determine the effect of lysozyme addition on in vitro
      rumen fermentation and to identify the lysozyme inclusion rate for abating
      methane (CH4) production. An in vitro ruminal fermentation technique was done
      using a commercial concentrate to rice straw ratio of 8:2 as substrate. The
      following treatments were applied wherein lysozyme was added into 1 mg dry matter
      substrate at different levels of inclusion: Without lysozyme, 2,000, 4,000, and
      8,000 U lysozyme. Results revealed that, lysozyme addition had a significant
      effect on pH after 24 h of incubation, with the highest pH (p<0.01) observed in
      8,000 U lysozyme, followed by the 4,000 U, 2,000 U, and without lysozyme. The
      highest amounts of acetic acid, propionic acid (p<0.01) and total volatile fatty
      acid (TVFA) (p<0.05) were found in 8,000 U after 24 h of incubation. The CH4
      concentration was the lowest in the 8,000 U and the highest in the without
      lysozyme addition after 24 h of incubation. There was no significant differences
      in general bacteria, methanogen, or protozoan DNA copy number. So far, addition
      of lysozyme increased the acetate, propionate, TVFA, and decreased CH4
      concentration. These results suggest that lysozyme supplementation may improve in
      vitro rumen fermentation and reduce CH4 emission.

PMID- 27703129
TI  - Overview of Brucellosis in Nepal.
AB  - Brucellosis is an abortifacient zoonotic disease which remains prominent in third
      world countries like Nepal. Brucellosis possess a public health concern, the
      incidences of which in livestocks can present substantial economic and health
      burdens for herders and health professionals. In Nepal, several cases of bovine
      including human brucellosis have been reported. This paper aims to evaluate the
      current status of the disease, the mechanism of infection, pathogenesis, zoonotic
      potential, diagnostic advances, treatment regimens, and the preventive measures
      that can be adopted in managing human brucellosis in under-developed countries
      like Nepal. Extensive review of all the available literatures in Nepal. Secondary
      information from various legitimate sources. There is a higher prevalence of
      Brucellosis among livestock but relatively lower prevalence among humans in Nepal
      as reported by many scholars. Lack of awareness, unhealthy food habit, orthodox
      husbandry practices, lack of surveillance and immunization has been the major
      factors in maintaining a vicious cycle of the disease maintenance and propagation
      in human and animals.

PMID- 27703131
TI  - Effects of age on intestinal phosphate transport and biochemical values of
      broiler chickens.
AB  - OBJECTIVE: The objective of this experiment was to characterize the mRNA
      expression profile of type IIb sodium-inorganic phosphate cotransporter (NaPi
      IIb) and the biochemical values of serum alkaline phosphatase (AKP), calcium,
      inorganic phosphorus, tibial ash and minerals of broiler chickens with aging.
      METHODS: A total of 56 one-day-old Arbor Acres male broiler chickens were used.
      Broiler chickens were weighed and samples were collected weekly from day 1.
      RESULTS: The result showed that before the growth inflection point, ash, calcium,
      and phosphorus content in the tibia of broiler chickens increased with growth
      (before 3 weeks of age), although there were no significant differences in chicks
      at different ages in the later period of the experiment and weight gain rate was
      relatively slow at this stage (4 to 6 weeks). NaPi-IIb gene expression in the
      small intestine in the early growth stage was higher than that in the later
      growth stage. Expression of calbindin and the vitamin D receptor protein in the
      intestinal mucosa increased with age in the duodenum and jejunum. Serum AKP
      activity first increased and subsequently decreased after peaking at 1 week of
      age, but there was no significant difference after 3 weeks of age. CONCLUSION:
      These results show that compared with the early growth stage, the weight-gain
      rate of broiler chickens in the late growth stage gradually decreased with
      gradual tibia maturation, along with weaker positive transport of phosphorus in
      the intestine and reinforced re-absorption of phosphorus in the kidney, which
      might be the reason that phosphorus requirement in the late growth stage was
      decreased.

PMID- 27703132
TI  - Multiple-enzyme supplementation on digestive traits, carcass characteristics,
      blood lipid parameters and growth performance of broilers fed a wheat-based diet.
AB  - OBJECTIVE: A trial was conducted from 11 to 42 d post-hatch to investigate the
      effectiveness of the supplementation of a multiple-enzyme preparation (Natuzyme
      Plus) in a wheat-based diet on digesta viscosity, pH and microbial population,
      villus morphology, feed passage time, nutrient retention, carcass
      characteristics, blood lipid parameters and growth performance of broiler
      chickens. METHODS: Three hundreds 10-d-old male Ross 308 chicks were allocated to
      three diets with five replicates of 20 birds per replicate. Dietary treatments
      were i) a wheat-based diet (W), ii) W+Natuzyme Plus (WN; 500 mg/kg of the diet),
      and iii) a corn-based diet (C). RESULTS: Birds fed on the C diet had higher
      average daily gain (ADG, p<0.01), villus height (VH, p<0.01), total tract
      apparent retention (TTAR) of nitrogen (NT, p<0.01) and ether extract (EE,
      p<0.01), nitrogen-corrected apparent metabolizable energy (AMEn, p<0.05),
      relative weight (RW, % of body weight) of carcass (p<0.05), blood concentration
      of triglyceride (TG, on d 40 [p<0.01]), total cholesterol (TC, on d 22 [p<0.05])
      and low density lipoprotein (LDL, on d 22 [p<0.01] and 40 [p<0.05]), and also
      lower feed conversion ratio (FCR, p<0.01), digesta viscosity (p<0.01), count of
      coliforms (p<0.01) and Escherichia coli (p<0.01) and epithelium thickness (ET,
      p<0.05) than those fed on the W diet. ADG, FCR, VH, ET, TTAR of NT and EE, RW of
      carcass, blood concentration of TG (on d 40), TC (on d 22) and LDL (on d 22 and
      40) values of the WN diet did not show a significant (p>0.05) difference compared
      to those of the C diet. Compared to those of the W diet, the WN diet showed the
      higher count of Lactobacilli and lower count of coliforms (p<0.01) and digesta
      viscosity (p<0.01). CONCLUSION: In general, the results of this study showed that
      Natuzyme Plus supplementation in a wheat-based diet can be appropriate to achieve
      a comparable growth performance in broiler chickens to those given the C diet
      probably through improving digesta viscosity, VH, ET, TTAR of NT and EE, AMEn,
      count of Lactobacilli and coliforms.

PMID- 27703133
TI  - Silage preparation and fermentation quality of natural grasses treated with
      lactic acid bacteria and cellulase in meadow steppe and typical steppe.
AB  - OBJECTIVE: In order to improve fermentation quality of natural grasses, their
      silage preparation and fermentation quality in meadow steppe (MS) and typical
      steppe (TS) were studied. METHODS: The small-scale silages and round bale silages
      of mixed natural grasses in both steppes were prepared using the commercial
      lactic acid bacteria (LAB) inoculants Chikuso-1 (CH, Lactobacillus plantarum) and
      cellulase enzyme (AC, Acremonium cellulase) as additives. RESULTS: MS and TS
      contained 33 and 9 species of natural grasses, respectively. Stipa baicalensis in
      MS and Stipa grandi in TS were the dominant grasses with the highest dry matter
      (DM) yield. The crude protein (CP), neutral detergent fiber and water-soluble
      carbohydrate of the mixed natural grasses in both steppes were 8.02% to 9.03%,
      66.75% to 69.47%, and 2.02% to 2.20% on a DM basis, respectively. All silages
      treated with LAB and cellulase were well preserved with lower pH, butyric acid
      and ammonia-N content, and higher lactic acid and CP content than those of
      control in four kinds of silages. Compared with CH- or AC-treated silages, the
      CH+ AC-treated silages had higher lactic acid content. CONCLUSION: The results
      confirmed that combination with LAB and cellulase may result in beneficial
      effects by improving the natural grass silage fermentation in both grasslands.

PMID- 27703134
TI  - Intracerebral and Intravenous Transplantation Represents a Favorable Approach for
      Application of Human Umbilical Cord Mesenchymal Stromal Cells in Intracerebral
      Hemorrhage Rats.
AB  - BACKGROUND Intracerebral hemorrhage (ICH) is one severe subtype of stroke, with a
      very complex pathology. Stem cell-based therapy holds promising potential in the
      treatment of neurological disorders. Human umbilical cord-derived mesenchymal
      stem cells (UC-MSCs) have a therapeutic effect in recovery from brain damage
      following ICH. The aim of this study was to identify an effective and convenient
      way of using UC-MSCs in the ICH rat model. MATERIAL AND METHODS CM-DiI-labeled
      human UC-MSCs were transplanted intracerebrally or intravenously into collagenase
      VII-induced ICH rat models. Neurological function was evaluated before ICH and at
      0, 7, 14, 21, and 28 days after treatment. ICH rats were sacrificed to evaluate
      the injury volume. Neurogenesis and angiogenesis and vascular areas were
      investigated using microtubule-associated protein 2 (MAP2), glial fibrillary
      acidic protein (GFAP), and 4',6-diamidino-2-phenylindole (DAPI)
      immunohistochemistry at two weeks after transplantation. RESULTS The
      intracerebral and intravenous administration of UC-MSCs both resulted in
      significant improvement in neurological function and decrease in injury volume of
      ICH rats. Transplanted UC-MSCs were chemotactic in vivo and showed a predominant
      distribution around the ICH region. In addition, UC-MSCs could integrate into the
      cerebral vasculature in both groups. CONCLUSIONS Both intracerebral and
      intravenous administration of UC-MSCs could have a favorable effect on recovery
      of neurological function in ICH rats, although the fundamental mechanisms may be
      different between the two groups. Our data suggest that intravenous implantation
      of UC-MSCs could serve as a favorable approach for cell-based therapy in central
      nervous system (CNS) diseases according to clinical needs.

PMID- 27703136
TI  - Enhancing stability and efficiency of perovskite solar cells with crosslinkable
      silane-functionalized and doped fullerene.
AB  - The instability of hybrid perovskite materials due to water and moisture arises
      as one major challenge to be addressed before any practical application of the
      demonstrated high efficiency perovskite solar cells. Here we report a facile
      strategy that can simultaneously enhance the stability and efficiency of p-i-n
      planar heterojunction-structure perovskite devices. Crosslinkable silane
      molecules with hydrophobic functional groups are bonded onto fullerene to make
      the fullerene layer highly water-resistant. Methylammonium iodide is introduced
      in the fullerene layer for n-doping via anion-induced electron transfer,
      resulting in dramatically increased conductivity over 100-fold. With
      crosslinkable silane-functionalized and doped fullerene electron transport layer,
      the perovskite devices deliver an efficiency of 19.5% with a high fill factor of
      80.6%. A crosslinked silane-modified fullerene layer also enhances the water and
      moisture stability of the non-sealed perovskite devices by retaining nearly 90%
      of their original efficiencies after 30 days' exposure in an ambient environment.

PMID- 27703137
TI  - Corrigendum: Retinal vessel caliber and its relationship with nocturnal blood
      pressure dipping status: the SABPA study.

PMID- 27703135
TI  - An extended genotyping framework for Salmonella enterica serovar Typhi, the cause
      of human typhoid.
AB  - The population of Salmonella enterica serovar Typhi (S. Typhi), the causative
      agent of typhoid fever, exhibits limited DNA sequence variation, which
      complicates efforts to rationally discriminate individual isolates. Here we
      utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced
      from over 60 countries to generate a robust genotyping scheme that is
      phylogenetically informative and compatible with a range of assays. These data
      show that, with the exception of the rapidly disseminating H58 subclade (now
      designated genotype 4.3.1), the global S. Typhi population is highly structured
      and includes dozens of subclades that display geographical restriction. The
      genotyping approach presented here can be used to interrogate local S. Typhi
      populations and help identify recent introductions of S. Typhi into new or
      previously endemic locations, providing information on their likely geographical
      source. This approach can be used to classify clinical isolates and provides a
      universal framework for further experimental investigations.

PMID- 27703139
TI  - Experimental determination of excitonic band structures of single-walled carbon
      nanotubes using circular dichroism spectra.
AB  - Experimental band structure analyses of single-walled carbon nanotubes have not
      yet been reported, to the best of our knowledge, except for a limited number of
      reports using scanning tunnelling spectroscopy. Here we demonstrate the
      experimental determination of the excitonic band structures of single-chirality
      single-walled carbon nanotubes using their circular dichroism spectra. In this
      analysis, we use gel column chromatography combining overloading selective
      adsorption with stepwise elution to separate 12 different single-chirality
      enantiomers. Our samples show higher circular dichroism intensities than the
      highest values reported in previous works, indicating their high enantiomeric
      purity. Excitonic band structure analysis is performed by assigning all observed
      Eii and Eij optical transitions in the circular dichroism spectra. The results
      reproduce the asymmetric structures of the valence and conduction bands predicted
      by density functional theory. Finally, we demonstrate that an extended empirical
      formula can estimate Eij optical transition energies for any (n,m) species.

PMID- 27703138
TI  - Environmental fatty acids enable emergence of infectious Staphylococcus aureus
      resistant to FASII-targeted antimicrobials.
AB  - The bacterial pathway for fatty acid biosynthesis, FASII, is a target for
      development of new anti-staphylococcal drugs. This strategy is based on previous
      reports indicating that self-synthesized fatty acids appear to be indispensable
      for Staphylococcus aureus growth and virulence, although other bacteria can use
      exogenous fatty acids to compensate FASII inhibition. Here we report that
      staphylococci can become resistant to the FASII-targeted inhibitor triclosan via
      high frequency mutations in fabD, one of the FASII genes. The fabD mutants can be
      conditional for FASII and not require exogenous fatty acids for normal growth,
      and can use diverse fatty acid combinations (including host fatty acids) when
      FASII is blocked. These mutants show cross-resistance to inhibitors of other
      FASII enzymes and are infectious in mice. Clinical isolates bearing fabD
      polymorphisms also bypass FASII inhibition. We propose that fatty acid-rich
      environments within the host, in the presence of FASII inhibitors, might favour
      the emergence of staphylococcal strains displaying resistance to multiple FASII
      inhibitors.

PMID- 27703140
TI  - Photonic crystals possessing multiple Weyl points and the experimental
      observation of robust surface states.
AB  - Weyl points, as monopoles of Berry curvature in momentum space, have captured
      much attention recently in various branches of physics. Realizing topological
      materials that exhibit such nodal points is challenging and indeed, Weyl points
      have been found experimentally in transition metal arsenide and phosphide and
      gyroid photonic crystal whose structure is complex. If realizing even the
      simplest type of single Weyl nodes with a topological charge of 1 is difficult,
      then making a real crystal carrying higher topological charges may seem more
      challenging. Here we design, and fabricate using planar fabrication technology, a
      photonic crystal possessing single Weyl points (including type-II nodes) and
      multiple Weyl points with topological charges of 2 and 3. We characterize this
      photonic crystal and find nontrivial 2D bulk band gaps for a fixed kz and the
      associated surface modes. The robustness of these surface states against kz
      preserving scattering is experimentally observed for the first time.

PMID- 27703141
TI  - Pre-eruptive magmatic processes re-timed using a non-isothermal approach to magma
      chamber dynamics.
AB  - Constraining the timescales of pre-eruptive magmatic processes in active volcanic
      systems is paramount to understand magma chamber dynamics and the triggers for
      volcanic eruptions. Temporal information of magmatic processes is locked within
      the chemical zoning profiles of crystals but can be accessed by means of
      elemental diffusion chronometry. Mineral compositional zoning testifies to the
      occurrence of substantial temperature differences within magma chambers, which
      often bias the estimated timescales in the case of multi-stage zoned minerals.
      Here we propose a new Non-Isothermal Diffusion Incremental Step model to take
      into account the non-isothermal nature of pre-eruptive processes, deconstructing
      the main core-rim diffusion profiles of multi-zoned crystals into different
      isothermal steps. The Non-Isothermal Diffusion Incremental Step model represents
      a significant improvement in the reconstruction of crystal lifetime histories.
      Unravelling stepwise timescales at contrasting temperatures provides a novel
      approach to constraining pre-eruptive magmatic processes and greatly increases
      our understanding of magma chamber dynamics.

PMID- 27703143
TI  - Observation of pendular butterfly Rydberg molecules.
AB  - Engineering molecules with a tunable bond length and defined quantum states lies
      at the heart of quantum chemistry. The unconventional binding mechanism of
      Rydberg molecules makes them a promising candidate to implement such tunable
      molecules. A very peculiar type of Rydberg molecules are the so-called butterfly
      molecules, which are bound by a shape resonance in the electron-perturber
      scattering. Here we report the observation of these exotic molecules and employ
      their exceptional properties to engineer their bond length, vibrational state,
      angular momentum and orientation in a small electric field. Combining the
      variable bond length with their giant dipole moment of several hundred Debye, we
      observe counter-intuitive molecules which locate the average electron position
      beyond the internuclear distance.

PMID- 27703142
TI  - Prokineticin-2 upregulation during neuronal injury mediates a compensatory
      protective response against dopaminergic neuronal degeneration.
AB  - Prokineticin-2 (PK2), a recently discovered secreted protein, regulates important
      physiological functions including olfactory biogenesis and circadian rhythms in
      the CNS. Interestingly, although PK2 expression is low in the nigral system, its
      receptors are constitutively expressed on nigrostriatal neurons. Herein, we
      demonstrate that PK2 expression is highly induced in nigral dopaminergic neurons
      during early stages of degeneration in multiple models of Parkinson's disease
      (PD), including PK2 reporter mice and MitoPark mice. Functional studies
      demonstrate that PK2 promotes mitochondrial biogenesis and activates ERK and Akt
      survival signalling pathways, thereby driving neuroprotection. Importantly, PK2
      overexpression is protective whereas PK2 receptor antagonism exacerbates
      dopaminergic degeneration in experimental PD. Furthermore, PK2 expression
      increased in surviving nigral dopaminergic neurons from PD brains, indicating
      that PK2 upregulation is clinically relevant to human PD. Collectively, our
      results identify a paradigm for compensatory neuroprotective PK2 signalling in
      nigral dopaminergic neurons that could have important therapeutic implications
      for PD.

PMID- 27703144
TI  - Bmi1 marks distinct castration-resistant luminal progenitor cells competent for
      prostate regeneration and tumour initiation.
AB  - Identification of defined cell populations with stem/progenitor properties is key
      for understanding prostate development and tumorigenesis. Here we show that the
      polycomb repressor protein Bmi1 marks a population of castration-resistant
      luminal epithelial cells enriched in the mouse proximal prostate. We employ
      lineage tracing to show that these castration-resistant Bmi1-expressing cells (or
      CARBs) are capable of tissue regeneration and self-renewal. Notably, CARBs are
      distinct from the previously described luminal castration-resistant Nkx3.1
      expressing cells (CARNs). CARBs can serve as a prostate cancer cell-of-origin
      upon Pten deletion, yielding luminal prostate tumours. Clonal analysis using the
      R26R-confetti allele indicates preferential tumour initiation from CARBs
      localized to the proximal prostate. These studies identify Bmi1 as a marker for a
      distinct population of castration-resistant luminal epithelial cells enriched in
      the proximal prostate that can serve as a cell of origin for prostate cancer.

PMID- 27703145
TI  - Biobank attributes associated with higher patient participation: a randomized
      study.
AB  - The objectives of the study were to assess patients' intent to participate in a
      hospital-based biobank and to explore the factors associated with higher
      participation. A 23-item questionnaire was developed to survey a random sample of
      patients in a Swiss university hospital. Two vignettes describing hypothetical
      biobanks were incorporated in the survey and patients were asked whether they
      would agree to participate. Three factors were randomly manipulated in each
      vignette using a factorial design: cancer-oriented research vs general consent,
      one vs several reviews of the patient's chart, and genetic vs blood protein
      analyses (first vignette); blood sample vs oral swabbing, local vs international
      project, and a follow-up visit vs no visit (second vignette). Of the 1140
      respondents, 73.6 and 69.6%, respectively, agreed to participate in the biobank.
      Biospecimen collection via oral swabbing, single chart review, and no follow-up
      were associated with higher participation. Participation was also higher among
      younger patients, Europeans, patients who had a positive opinion on research, and
      blood/organ donors. Biobanking was supported by a majority of patients,
      especially if biospecimens were collected through non-invasive techniques or if
      data collection was done once. The scope of consent, the scale of the project, or
      the tests performed on biospecimens did not influence participation.

PMID- 27703146
TI  - Improving the in silico assessment of pathogenicity for compensated variants.
AB  - Understanding the functional sequelae of amino-acid replacements is of
      fundamental importance in medical genetics. Perhaps, the most intuitive way to
      assess the potential pathogenicity of a given human missense variant is by
      measuring the degree of evolutionary conservation of the substituted amino-acid
      residue, a feature that generally serves as a good proxy metric for the
      functional/structural importance of that residue. However, the presence of
      putatively compensated variants as the wild-type alleles in orthologous proteins
      of other mammalian species not only challenges this classical view of amino-acid
      essentiality but also precludes the accurate evaluation of the functional impact
      of this type of missense variant using currently available bioinformatic
      prediction tools. Compensated variants constitute at least 4% of all known
      missense variants causing human-inherited disease and hence represent an
      important potential source of error in that they are likely to be
      disproportionately misclassified as benign variants. The consequent under
      reporting of compensated variants is exacerbated in the context of next
      generation sequencing where their inappropriate exclusion constitutes an
      unfortunate natural consequence of the filtering and prioritization of the very
      large number of variants generated. Here we demonstrate the reduced performance
      of currently available pathogenicity prediction tools when applied to compensated
      variants and propose an alternative machine-learning approach to assess likely
      pathogenicity for this particular type of variant.

PMID- 27703147
TI  - Variants in SKP1, PROB1, and IL17B genes at keratoconus 5q31.1-q35.3
      susceptibility locus identified by whole-exome sequencing.
AB  - Keratoconus (KTCN) is a protrusion and thinning of the cornea, resulting in
      impairment of visual function. The extreme genetic heterogeneity makes it
      difficult to discover factors unambiguously influencing the KTCN phenotype. In
      this study, we used whole-exome sequencing (WES) and Sanger sequencing to reduce
      the number of candidate genes at the 5q31.1-q35.3 locus and to prioritize other
      potentially relevant variants in an Ecuadorian family with KTCN. We applied WES
      in two affected KTCN individuals from the Ecuadorian family that showed a
      suggestive linkage between the KTCN phenotype and the 5q31.1-q35.3 locus.
      Putative variants identified by WES were further evaluated in this family using
      Sanger sequencing. Exome capture discovered a total of 173 rare (minor allele
      frequency <0.001 in control population) nonsynonymous variants in both affected
      individuals. Among them, 16 SNVs were selected for further evaluation.
      Segregation analysis revealed that variants c.475T>G in SKP1, c.671G>A in PROB1,
      and c.527G>A in IL17B in the 5q31.1-q35.3 linkage region, and c.850G>A in HKDC1
      in the 10q22 locus completely segregated with the phenotype in the studied KTCN
      family. We demonstrate that a combination of various techniques significantly
      narrowed the studied genomic region and reduced the list of the putative exonic
      variants. Moreover, since this locus overlapped two other chromosomal regions
      previously recognized in distinct KTCN studies, our findings suggest that this
      5q31.1-q35.3 locus might be linked with KTCN.

PMID- 27703148
TI  - The origin of efficient triplet state population in sulfur-substituted
      nucleobases.
AB  - Elucidating the photophysical mechanisms in sulfur-substituted nucleobases
      (thiobases) is essential for designing prospective drugs for photo- and
      chemotherapeutic applications. Although it has long been established that the
      phototherapeutic activity of thiobases is intimately linked to efficient
      intersystem crossing into reactive triplet states, the molecular factors
      underlying this efficiency are poorly understood. Herein we combine femtosecond
      transient absorption experiments with quantum chemistry and nonadiabatic dynamics
      simulations to investigate 2-thiocytosine as a necessary step to unravel the
      electronic and structural elements that lead to ultrafast and near-unity triplet
      state population in thiobases in general. We show that different parts of the
      potential energy surfaces are stabilized to different extents via thionation,
      quenching the intrinsic photostability of canonical DNA and RNA nucleobases.
      These findings satisfactorily explain why thiobases exhibit the fastest
      intersystem crossing lifetimes measured to date among bio-organic molecules and
      have near-unity triplet yields, whereas the triplet yields of canonical
      nucleobases are nearly zero.

PMID- 27703149
TI  - Variation in urinary spot sample, 24 h samples, and longer-term average urinary
      concentrations of short-lived environmental chemicals: implications for exposure
      assessment and reverse dosimetry.
AB  - Population biomonitoring data sets such as the Canadian Health Measures Survey
      (CHMS) and the United States National Health and Nutrition Examination Survey
      (NHANES) collect and analyze spot urine samples for analysis for biomarkers of
      exposure to non-persistent chemicals. Estimation of population intakes using such
      data sets in a risk-assessment context requires consideration of intra- and inter
      individual variability to understand the relationship between variation in the
      biomarker concentrations and variation in the underlying daily and longer-term
      intakes. Two intensive data sets with a total of 16 individuals with collection
      and measurement of serial urine voids over multiple days were used to examine
      these relationships using methyl paraben, triclosan, bisphenol A (BPA), monoethyl
      phthalate (MEP), and mono-2-ethylhexyl hydroxyl phthalate (MEHHP) as example
      compounds. Composited 24 h voids were constructed mathematically from the
      individual collected voids, and concentrations for each 24 h period and average
      multiday concentrations were calculated for each individual in the data sets.
      Geometric mean and 95th percentiles were compared to assess the relationship
      between distributions in spot sample concentrations and the 24 h and multiday
      collection averages. In these data sets, spot sample concentrations at the 95th
      percentile were similar to or slightly higher than the 95th percentile of the
      distribution of all 24 h composite void concentrations, but tended to
      overestimate the maximum of the multiday concentration averages for most analytes
      (usually by less than a factor of 2). These observations can assist in the
      interpretation of population distributions of spot samples for frequently
      detected analytes with relatively short elimination half-lives.

PMID- 27703151
TI  - Repeating microearthquake sequences interact predominantly through postseismic
      slip.
AB  - Studying small repeating earthquakes enables better understanding of fault
      physics and characterization of fault friction properties. Some of the nearby
      repeating sequences appear to interact, such as the 'San Francisco' and 'Los
      Angeles' repeaters on the creeping section of the San Andreas Fault. It is
      typically assumed that such interactions are induced by static stress changes due
      to coseismic slip. Here we present a study of the interaction of repeating
      earthquakes in the framework of rate-and-state fault models using state-of-the
      art simulation methods that reproduce both realistic seismic events and long-term
      earthquake sequences. Our simulations enable comparison among several types of
      stress transfer that occur between the repeating events. Our major finding is
      that postseismic creep dominates the interaction, with earthquake triggering
      occurring at distances much larger than typically assumed. Our results open a
      possibility of using interaction of repeating sequences to constrain friction
      properties of creeping segments.

PMID- 27703150
TI  - Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma.
AB  - Hepatitis B virus (HBV) can integrate into the human genome, contributing to
      genomic instability and hepatocarcinogenesis. Here by conducting high-throughput
      viral integration detection and RNA sequencing, we identify 4,225 HBV integration
      events in tumour and adjacent non-tumour samples from 426 patients with HCC. We
      show that HBV is prone to integrate into rare fragile sites and functional
      genomic regions including CpG islands. We observe a distinct pattern in the
      preferential sites of HBV integration between tumour and non-tumour tissues. HBV
      insertional sites are significantly enriched in the proximity of telomeres in
      tumours. Recurrent HBV target genes are identified with few that overlap. The
      overall HBV integration frequency is much higher in tumour genomes of males than
      in females, with a significant enrichment of integration into chromosome 17.
      Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting
      distinct targeted genes. Our data suggest that HBV integration has a high
      potential to drive oncogenic transformation.

PMID- 27703152
TI  - Thermopile detector of light ellipticity.
AB  - Polarimetric imaging is widely used in applications from material analysis to
      biomedical diagnostics, vision and astronomy. The degree of circular
      polarization, or light ellipticity, is associated with the S3 Stokes parameter
      which is defined as the difference in the intensities of the left- and right
      circularly polarized components of light. Traditional way of determining this
      parameter relies on using several external optical elements, such as polarizers
      and wave plates, along with conventional photodetectors, and performing at least
      two measurements to distinguish left- and right-circularly polarized light
      components. Here we theoretically propose and experimentally demonstrate a
      thermopile photodetector element that provides bipolar voltage output directly
      proportional to the S3 Stokes parameter of the incident light.

PMID- 27703154
TI  - Local adaptation (mostly) remains local: reassessing environmental associations
      of climate-related candidate SNPs in Arabidopsis halleri.
AB  - Numerous landscape genomic studies have identified single-nucleotide
      polymorphisms (SNPs) and genes potentially involved in local adaptation. Rarely,
      it has been explicitly evaluated whether these environmental associations also
      hold true beyond the populations studied. We tested whether putatively adaptive
      SNPs in Arabidopsis halleri (Brassicaceae), characterized in a previous study
      investigating local adaptation to a highly heterogeneous environment, show the
      same environmental associations in an independent, geographically enlarged set of
      18 populations. We analysed new SNP data of 444 plants with the same methodology
      (partial Mantel tests, PMTs) as in the original study and additionally with a
      latent factor mixed model (LFMM) approach. Of the 74 candidate SNPs, 41% (PMTs)
      and 51% (LFMM) were associated with environmental factors in the independent data
      set. However, only 5% (PMTs) and 15% (LFMM) of the associations showed the same
      environment-allele relationships as in the original study. In total, we found 11
      genes (31%) containing the same association in the original and independent data
      set. These can be considered prime candidate genes for environmental adaptation
      at a broader geographical scale. Our results suggest that selection pressures in
      highly heterogeneous alpine environments vary locally and signatures of selection
      are likely to be population-specific. Thus, genotype-by-environment interactions
      underlying adaptation are more heterogeneous and complex than is often assumed,
      which might represent a problem when testing for adaptation at specific loci.

PMID- 27703153
TI  - Heritable symbionts in a world of varying temperature.
AB  - Heritable microbes represent an important component of the biology, ecology and
      evolution of many plants, animals and fungi, acting as both parasites and
      partners. In this review, we examine how heritable symbiont-host interactions may
      alter host thermal tolerance, and how the dynamics of these interactions may more
      generally be altered by thermal environment. Obligate symbionts, those required
      by their host, are considered to represent a thermally sensitive weak point for
      their host, associated with accumulation of deleterious mutations. As such, these
      symbionts may represent an important determinant of host thermal envelope and
      spatial distribution. We then examine the varied relationship between thermal
      environment and the frequency of facultative symbionts that provide ecologically
      contingent benefits or act as parasites. We note that some facultative symbionts
      directly alter host thermotolerance. We outline how thermal environment will
      alter the benefits/costs of infection more widely, and additionally modulate
      vertical transmission efficiency. Multiple patterns are observed, with symbionts
      being cold sensitive in some species and heat sensitive in others, with varying
      and non-coincident thresholds at which phenotype and transmission are ablated.
      Nevertheless, it is clear that studies aiming to predict ecological and
      evolutionary dynamics of symbiont-host interactions need to examine the
      interaction across a range of thermal environments. Finally, we discuss the
      importance of thermal sensitivity in predicting the success/failure of symbionts
      to spread into novel species following natural/engineered introduction.

PMID- 27703155
TI  - Persistence of long-distance, insect-mediated pollen movement for a tropical
      canopy tree species in remnant forest patches in an urban landscape.
AB  - As deforestation and urbanization continue at rapid rates in tropical regions,
      urban forest patches are essential repositories of biodiversity. However, almost
      nothing is known about gene flow of forest-dependent tree species in urban
      landscapes. In this study, we investigated gene flow in the insect-pollinated,
      wind-dispersed tropical tree Koompassia malaccensis in and among three remnant
      forest patches in the urbanized landscape of Singapore. We genotyped the vast
      majority of adults (N=179) and a large number of recruits (N=2103) with 8 highly
      polymorphic microsatellite markers. Spatial genetic structure of the recruit and
      adult cohorts was significant, showing routine gene dispersal distances of ~100
      400 m. Parentage analysis showed that 97% of recruits were within 100 m of their
      mother tree, and a high frequency of relatively short-distance pollen dispersal
      (median ~143-187 m). Despite routine seed and pollen dispersal distances of
      within a few hundred meters, interpatch gene flow occurred between all patches
      and was dominated by pollen movement: parentage analysis showed 76 pollen versus
      2 seed interpatch dispersal events, and the seedling neighborhood model estimated
      ~1-6% seed immigration and ~21-46% pollen immigration rates, depending on patch.
      In addition, the smallest patch (containing five adult K. malaccensis trees) was
      entirely surrounded by >2.5 km of 'impervious' substrate, yet had the highest
      proportional pollen and seed immigration estimates of any patch. Hence, contrary
      to our hypothesis, insect-mediated gene flow persisted across an urban landscape,
      and several of our results also parallel key findings from insect-pollinated
      canopy trees sampled in mixed agricultural-forest landscapes.

PMID- 27703157
TI  - Animal diversity and ecosystem functioning in dynamic food webs.
AB  - Species diversity is changing globally and locally, but the complexity of
      ecological communities hampers a general understanding of the consequences of
      animal species loss on ecosystem functioning. High animal diversity increases
      complementarity of herbivores but also increases feeding rates within the
      consumer guild. Depending on the balance of these counteracting mechanisms,
      species-rich animal communities may put plants under top-down control or may
      release them from grazing pressure. Using a dynamic food-web model with body-mass
      constraints, we simulate ecosystem functions of 20,000 communities of varying
      animal diversity. We show that diverse animal communities accumulate more biomass
      and are more exploitative on plants, despite their higher rates of intra-guild
      predation. However, they do not reduce plant biomass because the communities are
      composed of larger, and thus energetically more efficient, plant and animal
      species. This plasticity of community body-size structure reconciles the debate
      on the consequences of animal species loss for primary productivity.

PMID- 27703158
TI  - Three structurally-related impurities in norvancomycin drug substance.
AB  - Norvancomycin (NVCM) is widely used in China to treat bacterial infections of
      Gram-positive cocci and bacilli, especially infections of methicillin-resistant
      Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis. This
      study is a chemical investigation of the drug substance of NVCM, and led to the
      identification, by 1D, 2D NMR spectra and HRESIMS, of three as yet undescribed
      impurities, one D-O-E ring expanded NVCM analog (1) and two derivatives of NVCM
      lacking sugars (2, 3).

PMID- 27703159
TI  - Synthesis and structure-activity relationships of novel lincomycin derivatives
      part 3: discovery of the 4-(pyrimidin-5-yl)phenyl group in synthesis of 7(S)
      thiolincomycin analogs.
AB  - Novel lincomycin derivatives possessing an aryl phenyl group or a heteroaryl
      phenyl group at the C-7 position via sulfur atom were synthesized by Pd-catalyzed
      cross-coupling reactions of 7(S)-7-deoxy-7-thiolincomycin (5) with various aryl
      halides. This reaction is the most useful method to synthesize a variety of 7(S)
      7-deoxy-7-thiolincomycin derivatives. On the basis of analysis of structure
      activity relationships of these novel lincomycin derivatives, we found that (a)
      the location of basicity in the C-7 side chain was an important factor to enhance
      antibacterial activities, and (b) compounds 22, 36, 42, 43 and 44 had potent
      antibacterial activities against a variety of Streptococcus pneumoniae with erm
      gene, which cause severe respiratory infections, even compared with our C-7
      modified lincomycin analogs (1-4) reported previously. Furthermore, 7(S)
      configuration was found to be necessary for enhancing antibacterial activities
      from comparison of configurations at the 7-position of 36 (S-configuration) and
      41 (R-configuration).

PMID- 27703156
TI  - Genome-wide compendium and functional assessment of in vivo heart enhancers.
AB  - Whole-genome sequencing is identifying growing numbers of non-coding variants in
      human disease studies, but the lack of accurate functional annotations prevents
      their interpretation. We describe the genome-wide landscape of distant-acting
      enhancers active in the developing and adult human heart, an organ whose
      impairment is a predominant cause of mortality and morbidity. Using integrative
      analysis of >35 epigenomic data sets from mouse and human pre- and postnatal
      hearts we created a comprehensive reference of >80,000 putative human heart
      enhancers. To illustrate the importance of enhancers in the regulation of genes
      involved in heart disease, we deleted the mouse orthologs of two human enhancers
      near cardiac myosin genes. In both cases, we observe in vivo expression changes
      and cardiac phenotypes consistent with human heart disease. Our study provides a
      comprehensive catalogue of human heart enhancers for use in clinical whole-genome
      sequencing studies and highlights the importance of enhancers for cardiac
      function.

PMID- 27703162
TI  - New national data show alarming increase in obesity and noncommunicable chronic
      diseases in China.

PMID- 27703160
TI  - Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast.
AB  - Rosemary extracts containing the phenolic diterpenes carnosic acid and its
      derivative carnosol are approved food additives used in an increasingly wide
      range of products to enhance shelf-life, thanks to their high anti-oxidant
      activity. We describe here the elucidation of the complete biosynthetic pathway
      of carnosic acid and its reconstitution in yeast cells. Cytochrome P450
      oxygenases (CYP76AH22-24) from Rosmarinus officinalis and Salvia fruticosa
      already characterized as ferruginol synthases are also able to produce 11
      hydroxyferruginol. Modelling-based mutagenesis of three amino acids in the
      related ferruginol synthase (CYP76AH1) from S. miltiorrhiza is sufficient to
      convert it to a 11-hydroxyferruginol synthase (HFS). The three sequential C20
      oxidations for the conversion of 11-hydroxyferruginol to carnosic acid are
      catalysed by the related CYP76AK6-8. The availability of the genes for the
      biosynthesis of carnosic acid opens opportunities for the metabolic engineering
      of phenolic diterpenes, a class of compounds with potent anti-oxidant, anti
      inflammatory and anti-tumour activities.

PMID- 27703161
TI  - Intake of vitamin B before onset of Parkinson's disease and atypical parkinsonism
      and olfactory function at the time of diagnosis.
AB  - BACKGROUND/OBJECTIVES: To investigate whether vitamin-B density in the diet 2-8
      years before diagnosis is associated with olfactory function at the time of
      diagnosis. SUBJECTS/METHODS: This prospective nested case-control study included
      patients with Parkinson's disease (PD), multiple system atrophy and progressive
      supranuclear paralysis identified between 2004 and 2009 in the county of
      Vasterbotten in northern Sweden. The case database (NYPUM study; Newly Diagnosed
      Parkinson in Umea; n=147) was cross-linked to the Northern Sweden Health and
      Disease Study (NSHDS). Identified patients (n=96) and controls (n=375) were
      matched for sex, age, year of health survey, sub-cohort and geographical area.
      Dietary intake was assessed by a food frequency questionnaire, and the brief
      smell identification test (B-SIT) was used to measure olfactory function at the
      time of diagnosis. RESULTS: There was no difference in vitamin-B or any other
      macro- or micro-nutrient densities, energy intake or body mass index (kg/m2; BMI)
      between patients and controls at baseline at the time of the healthcare survey. A
      lower thiamin and folate density, amount per 1 megajoule, was reported in
      patients who scored below median on B-SIT (<7) when compared with that in
      patients who scored ?7 at the time of diagnosis. After adjusting for age, sex and
      BMI using linear and logistic regressions, an even stronger association was found
      between thiamin density and olfactory function. CONCLUSIONS: A low thiamin and
      folate density in the reported diet, 2-8 years before PD diagnosis, was
      significantly associated with olfactory dysfunction at the time of PD diagnosis.

PMID- 27703163
TI  - Accuracy of non-paralytic anthropometric data for nutritional screening in older
      patients with stroke and hemiplegia.
AB  - BACKGROUND/OBJECTIVES: Although malnutrition commonly affects stroke patients,
      there are no validated screening tools. We verified the usefulness of non
      paralytic anthropometric measurements for the nutritional screening of stroke.
      SUBJECTS/METHODS: A cross-sectional study was conducted in consecutive stroke
      patients with hemiplegia aged ?65 years, with Mini Nutritional Assessment Short
      Form score ?11. Diagnostic malnutrition criteria from the European Society for
      Clinical Nutrition and Metabolism were the reference standards: body mass index
      (BMI) <18.5 kg/m2 or weight loss >10%+BMI <22 or 20 kg/m2. Non-paralytic
      anthropometric measurements (calf circumference (CC), arm circumference (AC),
      triceps skinfold (TSF) and arm muscle circumference (AMC)) and serum albumin
      concentration (Alb) at admission were the index tests. Cutoffs were determined by
      receiver operation curve and Youden index, and accuracy by area under the curve
      (AUC) and kappa value. Functional independence measures at discharge and
      discharge destination were collected. RESULTS: We included 488 patients (224 men
      and 264 women) with a mean age of 78.8 years and mean BMI of 22.0 and 21.1 kg/m2,
      respectively. Eighty-one men and 124 women had malnutrition. The AUC for CC, AC,
      TSF, AMC and Alb was 0.859, 0.825, 0.764, 0.745 and 0.670 for men, and 0.881,
      0.843, 0.796, 0.742 and 0.658 for women, respectively. In both sexes, CC had the
      highest kappa (0.533, 0.608; both P<0.001) with cutoff values ?31 and ?30 cm.
      Patients with lower CC showed significantly worse functional outcomes and lower
      proportion of return to home (P<0.001). CONCLUSIONS: Non-paralytic CC indicated
      malnutrition with sufficient accuracy and good correlation with functional
      capacity; it may be a useful nutritional screening tool for stroke.

PMID- 27703164
TI  - Analogue modulation of back-propagating action potentials enables dendritic
      hybrid signalling.
AB  - We report that back-propagating action potentials (bAPs) are not simply digital
      feedback signals in dendrites but also carry analogue information about the
      overall state of neurons. Analogue information about the somatic membrane
      potential within a physiological range (from -78 to -64 mV) is retained by bAPs
      of dentate gyrus granule cells as different repolarization speeds in proximal
      dendrites and as different peak amplitudes in distal regions. These location
      dependent waveform changes are reflected by local calcium influx, leading to
      proximal enhancement and distal attenuation during somatic hyperpolarization. The
      functional link between these retention and readout mechanisms of the analogue
      content of bAPs critically depends on high-voltage-activated, inactivating
      calcium channels. The hybrid bAP and calcium mechanisms report the phase of
      physiological somatic voltage fluctuations and modulate long-term synaptic
      plasticity in distal dendrites. Thus, bAPs are hybrid signals that relay somatic
      analogue information, which is detected by the dendrites in a location-dependent
      manner.

PMID- 27703165
TI  - Boosted output performance of triboelectric nanogenerator via electric double
      layer effect.
AB  - For existing triboelectric nanogenerators (TENGs), it is important to explore
      unique methods to further enhance the output power under realistic environments
      to speed up their commercialization. We report here a practical TENG composed of
      three layers, in which the key layer, an electric double layer, is inserted
      between a top layer, made of Al/polydimethylsiloxane, and a bottom layer, made of
      Al. The efficient charge separation in the middle layer, based on Volta's
      electrophorus, results from sequential contact configuration of the TENG and
      direct electrical connection of the middle layer to the earth. A sustainable and
      enhanced output performance of 1.22 mA and 46.8 mW cm-2 under low frequency of 3
      Hz is produced, giving over 16-fold enhancement in output power and corresponding
      to energy conversion efficiency of 22.4%. Finally, a portable power-supplying
      system, which provides enough d.c. power for charging a smart watch or phone
      battery, is also successfully developed.

PMID- 27703166
TI  - Structure sensitivity of Cu and CuZn catalysts relevant to industrial methanol
      synthesis.
AB  - For decades it has been debated whether the conversion of synthesis gas to
      methanol over copper catalysts is sensitive or insensitive to the structure of
      the copper surface. Here we have systematically investigated the effect of the
      copper particle size in the range where changes in surface structure occur, that
      is, below 10 nm, for catalysts with and without zinc promotor at industrially
      relevant conditions for methanol synthesis. Regardless of the presence or absence
      of a zinc promotor in the form of zinc oxide or zinc silicate, the surface
      specific activity decreases significantly for copper particles smaller than 8 nm,
      thus revealing structure sensitivity. In view of recent theoretical studies we
      propose that the methanol synthesis reaction takes place at copper surface sites
      with a unique configuration of atoms such as step-edge sites, which smaller
      particles cannot accommodate.

PMID- 27703167
TI  - Classical non-homologous end-joining pathway utilizes nascent RNA for error-free
      double-strand break repair of transcribed genes.
AB  - DNA double-strand breaks (DSBs) leading to loss of nucleotides in the transcribed
      region can be lethal. Classical non-homologous end-joining (C-NHEJ) is the
      dominant pathway for DSB repair (DSBR) in adult mammalian cells. Here we report
      that during such DSBR, mammalian C-NHEJ proteins form a multiprotein complex with
      RNA polymerase II and preferentially associate with the transcribed genes after
      DSB induction. Depletion of C-NHEJ factors significantly abrogates DSBR in
      transcribed but not in non-transcribed genes. We hypothesized that nascent RNA
      can serve as a template for restoring the missing sequences, thus allowing error
      free DSBR. We indeed found pre-mRNA in the C-NHEJ complex. Finally, when a DSB
      containing plasmid with several nucleotides deleted within the E. coli lacZ gene
      was allowed time to repair in lacZ-expressing mammalian cells, a functional lacZ
      plasmid could be recovered from control but not C-NHEJ factor-depleted cells,
      providing important mechanistic insights into C-NHEJ-mediated error-free DSBR of
      the transcribed genome.

PMID- 27703168
TI  - Determinants of carbon release from the active layer and permafrost deposits on
      the Tibetan Plateau.
AB  - The sign and magnitude of permafrost carbon (C)-climate feedback are highly
      uncertain due to the limited understanding of the decomposability of thawing
      permafrost and relevant mechanistic controls over C release. Here, by combining
      aerobic incubation with biomarker analysis and a three-pool model, we reveal that
      C quality (represented by a higher amount of fast cycling C but a lower amount of
      recalcitrant C compounds) and normalized CO2-C release in permafrost deposits
      were similar or even higher than those in the active layer, demonstrating a high
      vulnerability of C in Tibetan upland permafrost. We also illustrate that C
      quality exerts the most control over CO2-C release from the active layer, whereas
      soil microbial abundance is more directly associated with CO2-C release after
      permafrost thaw. Taken together, our findings highlight the importance of
      incorporating microbial properties into Earth System Models when predicting
      permafrost C dynamics under a changing environment.

PMID- 27703169
TI  - A key process controlling the wet removal of aerosols: new observational
      evidence.
AB  - The lifetime and spatial distributions of accumulation-mode aerosols in a size
      range of approximately 0.05-1 MUm, and thus their global and regional climate
      impacts, are primarily constrained by their removal via cloud and precipitation
      (wet removal). However, the microphysical process that predominantly controls the
      removal efficiency remains unidentified because of observational difficulties.
      Here, we demonstrate that the activation of aerosols to cloud droplets
      (nucleation scavenging) predominantly controls the wet removal efficiency of
      accumulation-mode aerosols, using water-insoluble black carbon as an observable
      particle tracer during the removal process. From simultaneous ground-based
      observations of black carbon in air (prior to removal) and in rainwater (after
      removal) in Tokyo, Japan, we found that the wet removal efficiency depends
      strongly on particle size, and the size dependence can be explained
      quantitatively by the observed size-dependent cloud-nucleating ability.
      Furthermore, our observational method provides an estimate of the effective
      supersaturation of water vapour in precipitating cloud clusters, a key parameter
      controlling nucleation scavenging. These novel data firmly indicate the
      importance of quantitative numerical simulations of the nucleation scavenging
      process to improve the model's ability to predict the atmospheric aerosol burden
      and the resultant climate forcings, and enable a new validation of such
      simulations.

PMID- 27703170
TI  - A cytosolic carbonic anhydrase molecular switch occurs in the gills of
      metamorphic sea lamprey.
AB  - Carbonic anhydrase plays a key role in CO2 transport, acid-base and ion
      regulation and metabolic processes in vertebrates. While several carbonic
      anhydrase isoforms have been identified in numerous vertebrate species, basal
      lineages such as the cyclostomes have remained largely unexamined. Here we
      investigate the repertoire of cytoplasmic carbonic anhydrases in the sea lamprey
      (Petromyzon marinus), that has a complex life history marked by a dramatic
      metamorphosis from a benthic filter-feeding ammocoete larvae into a parasitic
      juvenile which migrates from freshwater to seawater. We have identified a novel
      carbonic anhydrase gene (ca19) beyond the single carbonic anhydrase gene (ca18)
      that was known previously. Phylogenetic analysis and synteny studies suggest that
      both carbonic anhydrase genes form one or two independent gene lineages and are
      most likely duplicates retained uniquely in cyclostomes. Quantitative PCR of ca19
      and ca18 and protein expression in gill across metamorphosis show that the ca19
      levels are highest in ammocoetes and decrease during metamorphosis while ca18
      shows the opposite pattern with the highest levels in post-metamorphic juveniles.
      We propose that a unique molecular switch occurs during lamprey metamorphosis
      resulting in distinct gill carbonic anhydrases reflecting the contrasting life
      modes and habitats of these life-history stages.

PMID- 27703171
TI  - Metabolomic Analysis of Mouse Embryonic Fibroblast Cells in Response to Autophagy
      Induced by Acute Starvation.
AB  - Autophagy-related protein 7 (Atg7) is essential in the formation of the
      autophagophore and is indispensable for autophagy induction. Autophagy will exist
      in lower level or even be blocked in cells without Atg7. Even though the possible
      signaling pathways of Atg7 have been proposed, the metabolomic responses under
      acute starvation in cells with and without Atg7 have not been elucidated. This
      study therefore was designed and aimed to reveal the metabolomics of Atg7
      dependent autophagy through metabolomic analysis of Atg7-/- mouse embryonic
      fibroblast cells (MEFs) and wild-type MEFs along with the starvation time. 30
      significantly altered metabolites were identified in response to nutrient stress,
      which were mainly associated with amino acid, energy, carbohydrate, and lipid
      metabolism. For the wild-type MEFs, the induction of autophagy protected cell
      survival with some up-regulated lipids during the first two hours' starvation,
      while the subsequent apoptosis resulted in the decrease of cell viability after
      four hours' starvation. For the Atg7-/- MEFs, apoptosis perhaps led to the
      deactivation of tricarboxylic acid (TCA) cycle due to the lack of autophagy,
      which resulted in the immediate drop of cellular viability under starvation.
      These results contributed to the metabolomic study and provided new insights into
      the mechanism associated with Atg7-dependent autophagy.

PMID- 27703172
TI  - A Tetravalent Sub-unit Dengue Vaccine Formulated with Ionizable Cationic Lipid
      Nanoparticle induces Significant Immune Responses in Rodents and Non-Human
      Primates.
AB  - Dengue virus has emerged as an important arboviral infection worldwide. As a
      complex pathogen, with four distinct serotypes, the development of a successful
      Dengue virus vaccine has proven to be challenging. Here, we describe a novel
      Dengue vaccine candidate that contains truncated, recombinant, Dengue virus
      envelope protein from all four Dengue virus serotypes (DEN-80E) formulated with
      ionizable cationic lipid nanoparticles (LNPs). Immunization studies in mice,
      Guinea pigs, and in Rhesus macaques, revealed that LNPs induced high titers of
      Dengue virus neutralizing antibodies, with or without co-administration or
      encapsulation of a Toll-Like Receptor 9 agonist. Importantly, LNPs were also able
      to boost DEN-80E specific CD4+ and CD8+ T cell responses. Cytokine and chemokine
      profiling revealed that LNPs induced strong chemokine responses without
      significant induction of inflammatory cytokines. In addition to being highly
      efficacious, the vaccine formulation proved to be well-tolerated, demonstrating
      no elevation in any of the safety parameters evaluated. Notably, reduction in
      cationic lipid content of the nanoparticle dramatically reduced the LNP's ability
      to boost DEN-80E specific immune responses, highlighting the crucial role for the
      charge of the LNP. Overall, our novel studies, across multiple species, reveal a
      promising tetravalent Dengue virus sub-unit vaccine candidate.

PMID- 27703174
TI  - Light-Controlled ZrO2 Surface Hydrophilicity.
AB  - In recent years many works are aimed at finding a method of controllable
      switching between hydrophilicity and hydrophobicity of a surface. The hydrophilic
      surface state is generally determined by its energy. Change in the surface energy
      can be realized in several different ways. Here we report the ability to control
      the surface wettability of zirconium dioxide nano-coatings by changing the
      composition of actinic light. Such unique photoinduced hydrophilic behavior of
      ZrO2 surface is ascribed to the formation of different active surface states
      under photoexcitation in intrinsic and extrinsic ZrO2 absorption regions. The
      sequential effect of different actinic lights on the surface hydrophilicity of
      zirconia is found to be repeatable and reversibly switchable from a highly
      hydrophilic state to a more hydrophobic state. The observed light-controllable
      reversible and reproducible switching of hydrophilicity opens new possible ways
      for the application of ZrO2 based materials.

PMID- 27703173
TI  - Risk of prenatal depression and stress treatment: alteration on serotonin system
      of offspring through exposure to Fluoxetine.
AB  - Fluoxetine is widely used to treat depression, including depression in pregnant
      and postpartum women. Studies suggest that fluoxetine may have adverse effects on
      offspring, presumably through its action on various serotonin receptors (HTRs).
      However, definitive evidence and the underlying mechanisms are largely
      unavailable. As initial steps towards establishing a human cellular and animal
      model, we analyzed the expression patterns of several HTRs through the
      differentiation of human induced pluripotent stem (hiPS) cells into neuronal
      cells, and analyzed expression pattern in zebrafish embryos. Treatment of
      zebrafish embryos with fluoxetine significantly blocked the expression of
      multiple HTRs. Furthermore, fluoxetine gave rise to a change in neuropsychology.
      Embryos treated with fluoxetine continued to exhibit abnormal behavior upto 12
      days post fertilization due to changes in HTRs. These findings support a possible
      long-term risk of serotonin pathway alteration, possibly resulting from the
      "placental drug transfer".

PMID- 27703176
TI  - Large Absorption Enhancement in Ultrathin Solar Cells Patterned by Metallic
      Nanocavity Arrays.
AB  - A new type of light trapping structure utilizing ring-shaped metallic nanocavity
      arrays is proposed for the absorption enhancement in ultrathin solar cells with
      few photonic waveguide modes. Dozens of times of broadband absorption enhancement
      in the spectral range of 700 to 1100 nm is demonstrated in an ultrathin Si3N4/c
      Si/Ag prototype solar cell by means of finite-difference time-domain (FDTD)
      simulation, and this dramatic absorption enhancement can be attributed to the
      excitation of plasmonic cavity modes in these nanocavity arrays. The cavity modes
      optimally compensate for the lack of resonances in the longer wavelength range
      for ultrathin solar cells, and eventually a maximum Jsc enhancement factor of
      2.15 is achieved under AM 1.5G solar illumination. This study opens a new
      perspective for light management in thin film solar cells and other
      optoelectronic devices.

PMID- 27703175
TI  - Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced
      Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and
      Smad7.
AB  - Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis
      therapy, due to their potential ability of inhibiting cardiac myofibroblast
      differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved
      in their effects remains elusive. To explore this, it is necessary to develop an
      in vitro cardiac fibrosis model that incorporates pore size and native tissue
      mimicking matrix stiffness, which may regulate cardiac myofibroblast
      differentiation. In the present study, collagen coated polyacrylamide hydrogel
      substrates were fabricated, in which the pore size was adjusted without altering
      the matrix stiffness. Stiffness is shown to regulate cardiac myofibroblast
      differentiation independently of pore size. Substrate at a stiffness of 30 kPa,
      which mimics the stiffness of native fibrotic cardiac tissue, was found to induce
      cardiac myofibroblast differentiation to create in vitro cardiac fibrosis model.
      Conditioned medium of hMSCs was applied to the model to determine its role and
      inhibitory mechanism on cardiac myofibroblast differentiation. It was found that
      hMSCs secrete hepatocyte growth factor (HGF) to inhibit cardiac myofibroblast
      differentiation via downregulation of angiotensin II type 1 receptor (AT1R) and
      upregulation of Smad7. These findings would aid in establishment of the
      therapeutic use of hMSCs in cardiac fibrosis therapy in future.

PMID- 27703177
TI  - Necrostatin-1 treatment inhibits osteocyte necroptosis and trabecular
      deterioration in ovariectomized rats.
AB  - Estrogen (E2) deficiency has been associated with accelerated osteocyte
      apoptosis. Our previous study showed necroptosis accelerated the loss of
      osteocytes in E2 deficiency-induced osteoporosis in rats in addition to
      apoptosis, but the mechanism involved remains. Necroptosis is a caspase
      independent form of programmed cell death. In the necroptosis pathway, receptor
      interaction proteins 1 and 3 (RIP1/3) play vital roles. Necrostatin-1 (Nec-1) has
      been confirmed to be a specific inhibitor of necroptosis. However, the effect of
      Nec-1 on postmenopausal osteoporosis remains ambiguous. The aim of this study was
      to investigate the effect of Nec-1 on osteocytes in ovariectomized (OVX) rats. We
      found that an increased number of necroptotic osteocytes was related to the
      production of tumor necrosis factor-alpha (TNF-alpha) in OVX rats. Treatment with
      Nec-1 significantly decreased RIP1 and RIP3 expression in OVX rats and inhibited
      osteocyte necroptosis induced by TNF-alpha in vitro. Both E2 and Nec-1 treatment
      markedly ameliorated trabecular bone deterioration. Nec-1 also significantly
      elevated the levels of bone formation markers and decreased bone resorption
      markers. These data suggest that the role of Nec-1 on alleviating bone loss might
      be associated with Nec-1 restraining TNF-alpha-induced osteocyte necroptosis in
      rats with E2 deficiency-induced osteoporosis. This process may represent a novel
      therapeutic strategy for the treatment of postmenopausal osteoporosis.

PMID- 27703178
TI  - Rapid genomic changes in allopolyploids of Carassius auratus red var. (?) *
      Megalobrama amblycephala (?).
AB  - To better understand genomic changes in the early generations after
      polyploidisation, we examined the chromosomal consequences of genomic merger in
      allotetraploid hybrids (4 nF1) (AABB, 4n = 148) of Carassius auratus red var.
      (RCC) (AA, 2n = 100) (?) * Megalobrama amblycephala (BSB) (BB, 2n = 48) (?).
      Complete loss of the paternal 5S rDNA sequence and the expected number of
      maternal chromosomal loci were found in 4 nF1, suggesting directional genomic
      changes occurred in the first generations after polyploidisation. Recent studies
      have reported instability of newly established allotetraploid genomes. To assess
      this in the newly formed 4 nF1 genome, we performed fluorescence in situ
      hybridisation on an allotetraploid gynogenetic hybrid (4 nG) (AABB, 4n = 148) and
      an allopentaploid hybrid (5 nH) (AABBB, 5n = 172) from 4 nF1 (?) * BSB (?) with
      5S rDNA gene and centromere probes from RCC, the original diploid parent. The
      expected numbers of maternal chromosomal loci were found in 4 nG, while
      chromosomal locus deletions and chromosome recombinations were detected in 5 nH.
      These observations suggest that abnormal meiosis did not lead to obvious genomic
      changes in the newly established allotetraploid genomes, but hybridisation with
      the original diploid parent resulted in obvious genomic changes in the newly
      established allotetraploid genomes, as was found for the maternal genome.

PMID- 27703180
TI  - Room-temperature near-infrared up-conversion lasing in single-crystal Er-Y
      chloride silicate nanowires.
AB  - Near-infrared up-conversion lasing in erbium(Er)-yttrium(Y) chloride silicate
      nanowires was demonstrated when pumped by 1476 nm laser at room temperature. The
      emission covers a very wide wavelength range (400-1000 nm). A clear threshold for
      985 nm peak was observed at a launched average pump power of approximately 7 mW.
      Above threshold, the intensity increases linearly when turning up the pump power.
      The full width at half maximum at 985 nm decreases from 1.25 nm to 0.25 nm when
      reducing the measurement temperature from 30 K to 7 K, which is the narrowest
      linewidth of 980 nm micro-lasers to date. Our demonstration presents a possible
      novel method of utilizing up-conversion mechanism in Er-Y nanowire to achieve
      tunable near-infrared laser, which breaks new ground in the exploration of
      nanoscale optoelectronic devices operating at near-infrared wavelength.

PMID- 27703179
TI  - Mining gut microbiome oligopeptides by functional metaproteome display.
AB  - Pathogen infections, autoimmune diseases, and chronic inflammatory disorders are
      associated with systemic antibody responses from the host immune system. Disease
      specific antibodies can be important serum biomarkers, but the identification of
      antigens associated with specific immune reactions is challenging, in particular
      if complex communities of microorganisms are involved in the disease progression.
      Despite promising new diagnostic opportunities, the discovery of these
      serological markers becomes more difficult with increasing complexity of
      microbial communities. In the present work, we used a metagenomic M13 phage
      display approach to select immunogenic oligopeptides from the gut microbiome of
      transgenic mice suffering from chronic ileitis. We constructed three individual
      metaproteome phage display libraries with a library size of approximately 107
      clones each. Using serum antibodies, we selected and validated three
      oligopeptides that induced specific antibody responses in the mouse model. This
      proof-of-concept study provides the first successful application of functional
      metaproteome display for the study of protein-protein interactions and the
      discovery of potential disease biomarkers.

PMID- 27703181
TI  - Corrigendum: A fast and unbiased procedure to randomize ecological binary
      matrices with fixed row and column totals.

PMID- 27703182
TI  - Silver Nanowire-IZO-Conducting Polymer Hybrids for Flexible and Transparent
      Conductive Electrodes for Organic Light-Emitting Diodes.
AB  - Solution-processed silver nanowire (AgNW) has been considered as a promising
      material for next-generation flexible transparent conductive electrodes. However,
      despite the advantages of AgNWs, some of their intrinsic drawbacks, such as large
      surface roughness and poor interconnection between wires, limit their practical
      application in organic light-emitting diodes (OLEDs). Herein, we report a high
      performance AgNW-based hybrid electrode composed of indium-doped zinc oxide (IZO)
      and poly (3,4-ethylenediowythiophene):poly(styrenesulfonate) [PEDOT:PSS]. The IZO
      layer protects the underlying AgNWs from oxidation and corrosion and tightly
      fuses the wires together and to the substrate. The PEDOT:PSS effectively reduces
      surface roughness and increases the hybrid films' transmittance. The fabricated
      electrodes exhibited a low sheet resistance of 5.9 Omegasq-1 with high
      transmittance of 86% at 550 nm. The optical, electrical, and mechanical
      properties of the AgNW-based hybrid films were investigated in detail to
      determine the structure-property relations, and whether optical or electrical
      properties could be controlled with variation in each layer's thickness to
      satisfy different requirements for different applications. Flexible OLEDs (f
      OLEDs) were successfully fabricated on the hybrid electrodes to prove their
      applicability; their performance was even better than those on commercial indium
      doped tin oxide (ITO) electrodes.

PMID- 27703183
TI  - Erratum: Magnetic measurements with atomic-plane resolution.

PMID- 27703184
TI  - Elastic Scattering Spectroscopy (ESS): an Instrument-Concept for Dynamics of
      Complex (Bio-) Systems From Elastic Neutron Scattering.
AB  - A new type of neutron-scattering spectroscopy is presented that is designed
      specifically to measure dynamics in bio-systems that are difficult to obtain in
      any other way. The temporal information is largely model-free and is analogous to
      relaxation processes measured with dielectric spectroscopy, but provides
      additional spacial and geometric aspects of the underlying dynamics. Numerical
      simulations of the basic instrument design show the neutron beam can be highly
      focussed, giving efficiency gains that enable the use of small samples. Although
      we concentrate on continuous neutron sources, the extension to pulsed neutron
      sources is proposed, both requiring minimal data-treatment and being broadly
      analogous with dielectric spectroscopy, they will open the study of dynamics to
      new areas of biophysics.

PMID- 27703185
TI  - Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan
      Filovirus Vaccine.
AB  - Epigraph is an efficient graph-based algorithm for designing vaccine antigens to
      optimize potential T-cell epitope (PTE) coverage. Epigraph vaccine antigens are
      functionally similar to Mosaic vaccines, which have demonstrated effectiveness in
      preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm,
      Epigraph is substantially faster, and in restricted cases, provides a
      mathematically optimal solution. Epigraph furthermore has new features that
      enable enhanced vaccine design flexibility. These features include the ability to
      exclude rare epitopes from a design, to optimize population coverage based on
      inexact epitope matches, and to apply the code to both aligned and unaligned
      input sequences. Epigraph was developed to provide practical design solutions for
      two outstanding vaccine problems. The first of these is a personalized approach
      to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent
      match to an individual's infecting strain, intended to contain or clear a chronic
      infection. The second is a pan-filovirus vaccine, with the potential to protect
      against all known viruses in the Filoviradae family, including ebolaviruses. A
      web-based interface to run the Epigraph tool suite is available
      (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).

PMID- 27703187
TI  - Polymer Nanodot-Hybridized Alkyl Silicon Oxide Nanostructures for Organic Memory
      Transistors with Outstanding High-Temperature Operation Stability.
AB  - Organic memory devices (OMDs) are becoming more important as a core component in
      flexible electronics era because of their huge potentials for ultrathin,
      lightweight and flexible plastic memory modules. In particular, transistor-type
      OMDs (TOMDs) have been gradually spotlighted due to their structural advantages
      possessing both memory and driving functions in single devices. Although a
      variety of TOMDs have been developed by introducing various materials, less
      attention has been paid to the stable operation at high temperatures. Here we
      demonstrate that the polymer nanodot-embedded alkyl silicon oxide (ASiO) hybrid
      materials, which are prepared by sol-gel and thermal cross-linking reactions
      between poly(4-vinylphenol) (PVP) and vinyltriethoxysilane, can deliver low
      voltage (1~5 V) TOMDs with outstanding operation stability (>4700 cycles) at high
      temperatures (150  degrees C). The efficient low-voltage memory function is
      enabled by the embedded PVP nanodots with particular lattice nanostructures,
      while the high thermal stability is achieved by the cross-linked ASiO network
      structures.

PMID- 27703188
TI  - The Impact of Li Grain Size on Coulombic Efficiency in Li Batteries.
AB  - One of the most promising means to increase the energy density of state-of-the
      art lithium Li-ion batteries is to replace the graphite anode with a Li metal
      anode. While the direct use of Li metal may be highly advantageous, at present
      its practical application is limited by issues related to dendrite growth and low
      Coulombic efficiency, CE. Here operando electrochemical scanning transmission
      electron microscopy (STEM) is used to directly image the deposition/stripping of
      Li at the anode-electrolyte interface in a Li-based battery. A non-aqueous
      electrolyte containing small amounts of H2O as an additive results in remarkably
      different deposition/stripping properties as compared to the "dry" electrolyte
      when operated under identical electrochemical conditions. The electrolyte with
      the additive deposits more Li during the first cycle, with the grain sizes of the
      Li deposits being significantly larger and more variable. The stripping of the Li
      upon discharge is also more complete, i.e., there is a higher cycling CE. This
      suggests that larger grain sizes are indicative of better performance by leading
      to more uniform Li deposition and an overall decrease in the formation of Li
      dendrites and side reactions with electrolyte components, thus potentially paving
      the way for the direct use of Li metal in battery technologies.

PMID- 27703186
TI  - Matrix factorization reveals aging-specific co-expression gene modules in the fat
      and muscle tissues in nonhuman primates.
AB  - Accurate identification of coherent transcriptional modules (subnetworks) in
      adipose and muscle tissues is important for revealing the related mechanisms and
      co-regulated pathways involved in the development of aging-related diseases.
      Here, we proposed a systematically computational approach, called ICEGM, to
      Identify the Co-Expression Gene Modules through a novel mathematical framework of
      Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was
      applied on the adipose, and heart and skeletal muscle tissues in old and young
      female African green vervet monkeys. The genes associated with the development of
      inflammation, cardiovascular and skeletal disorder diseases, and cancer were
      revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched
      in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells.
      Comprehensive disease annotation and canonical pathway analysis indicated that
      immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a
      synergistic role in cardiac and physical functions in the aged monkeys by
      regulation of the biological processes associated with metabolism, inflammation,
      and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic
      framework for decoding the co-expression gene modules in multiple tissues.
      Analysis of genes in the ICEGM module yielded important insights on the
      cooperative role of multiple tissues in the development of diseases.

PMID- 27703190
TI  - Association of interleukin 16 gene polymorphisms and plasma IL16 level with
      osteosarcoma risk.
AB  - Interleukin (IL) 16 plays a key role in inflammatory diseases as well as in
      tumorigenesis of osteosarcoma (OS). The aim of this study was to investigate the
      association of IL16 polymorphisms and plasma IL16 level with OS risk in a Chinese
      population. We genotyped IL16 rs4778889, rs11556218, and rs4072111 in 358
      patients with OS and 402 controls using a polymerase chain reaction-restriction
      fragment length polymorphism assay. Plasma IL16 level was measured by enzyme
      linked immunosorbent assay. Rs11556218 was associated with an increased risk of
      OS in heterozygote comparison (adjusted OR = 1.65, 95% CI, 1.23-2.21, P < 0.001),
      dominant model (adjusted OR = 1.66, 95% CI, 1.24-2.21, P < 0.001), and allele
      comparison (adjusted OR = 1.44, 95% CI, 1.14-1.81, P = 0.002). Moreover,
      rs11556218 TG/GG genotypes were associated with higher levels of IL16 as compared
      to TT genotype (P = 0.03). However, no significant association of rs4778889 and
      rs4072111 and OS was found. These findings suggest that rs11556218 TG/GG
      genotypes may be associated with increased susceptibility to OS, probably by
      increasing the production of IL16 level.

PMID- 27703189
TI  - Dissection of brassinosteroid-regulated proteins in rice embryos during
      germination by quantitative proteomics.
AB  - Brassinosteroids (BRs), essential plant-specific steroidal hormones, function in
      a wide spectrum of plant growth and development events, including seed
      germination. Rice is not only a monocotyledonous model plant but also one of the
      most important staple food crops of human beings. Rice seed germination is a
      decisive event for the next-generation of plant growth and successful seed
      germination is critical for rice yield. However, little is known about the
      molecular mechanisms on how BR modulates seed germination in rice. In the present
      study, we used isobaric tags for relative and absolute quantification (iTRAQ)
      based proteomic approach to study BR-regulated proteome during the early stage of
      seed germination. The results showed that more than 800 BR-responsive proteins
      were identified, including 88 reliable target proteins responsive to stimuli of
      both BR-deficiency and BR-insensitivity. Moreover, 90% of the 88 target proteins
      shared a similar expression change pattern. Gene ontology and string analysis
      indicated that ribosomal structural proteins, as well as proteins involved in
      protein biosynthesis and carbohydrate metabolisms were highly clustered. These
      findings not only enrich BR-regulated protein database in rice seeds, but also
      allow us to gain novel insights into the molecular mechanism of BR regulated seed
      germination.

PMID- 27703191
TI  - Measuring populations to improve vaccination coverage.
AB  - In low-income settings, vaccination campaigns supplement routine immunization but
      often fail to achieve coverage goals due to uncertainty about target population
      size and distribution. Accurate, updated estimates of target populations are rare
      but critical; short-term fluctuations can greatly impact population size and
      susceptibility. We use satellite imagery to quantify population fluctuations and
      the coverage achieved by a measles outbreak response vaccination campaign in
      urban Niger and compare campaign estimates to measurements from a post-campaign
      survey. Vaccine coverage was overestimated because the campaign underestimated
      resident numbers and seasonal migration further increased the target population.
      We combine satellite-derived measurements of fluctuations in population
      distribution with high-resolution measles case reports to develop a dynamic model
      that illustrates the potential improvement in vaccination campaign coverage if
      planners account for predictable population fluctuations. Satellite imagery can
      improve retrospective estimates of vaccination campaign impact and future
      campaign planning by synchronizing interventions with predictable population
      fluxes.

PMID- 27703192
TI  - GDF11 improves tubular regeneration after acute kidney injury in elderly mice.
AB  - The GDF11 expression pattern and its effect on organ regeneration after acute
      injury in the elderly population are highly controversial topics. In our study,
      GDF11/8 expression increased after kidney ischemia-reperfusion injury (IRI), and
      the relatively lower level of GDF11/8 in the kidneys of aged mice was associated
      with a loss of proliferative capacity and a decline in renal repair, compared to
      young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and
      Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2'
      deoxyuridine (EdU)-positive proximal tubular epithelial cells. GDF11 improved the
      renal repair, recovery of renal function, and survival of elderly mice at 72 h
      after IRI. Moreover, the addition of recombinant GDF11 to primary renal
      epithelial cells increased proliferation, migration, and dedifferentiation by
      upregulating the ERK1/2 pathway in vitro. Our study indicates that GDF11/8 in the
      kidney decreases with age and that GDF11 can increase tubular cell
      dedifferentiation and proliferation as well as improve tubular regeneration after
      acute kidney injury (AKI) in old mice.

PMID- 27703193
TI  - Genes implicated in thiopurine-induced toxicity: Comparing TPMT enzyme activity
      with clinical phenotype and exome data in a paediatric IBD cohort.
AB  - The aim of our study was to assess the utility of next generation sequencing
      (NGS) for predicting toxicity and clinical response to thiopurine drugs in
      paediatric patients with inflammatory bowel disease. Exome data for 100 patients
      were assessed against biochemically measured TPMT enzyme activity, clinical
      response and adverse effects. The TPMT gene and a panel of 15 other genes
      implicated in thiopurine toxicity were analysed using a gene based statistical
      test (SKAT-O test). Nine patients out of 100 (Crohn's disease- 67, ulcerative
      colitis- 23 and IBDU-10) had known TPMT mutations associated with deficient
      enzyme activity. A novel and a highly pathogenic TPMT variant not detectable
      through standard genotyping, was identified through NGS in an individual
      intolerant to thiopurines. Of the 14 patients intolerant to thiopurines, NGS
      identified deleterious TPMT variants in 5 individuals whereas the biochemical
      test identified 8 individuals as intolerant (sensitivity 35.7% and 57.14%;
      specificity 93.75% and 50% respectively). SKAT-O test identified a significant
      association between MOCOS gene and TPMT activity (p = 0.0015), not previously
      reported. Although NGS has the ability to detect rare or novel variants not
      otherwise identified through standard genotyping, it demonstrates no clear
      advantage over the biochemical test in predicting toxicity in our modest cohort.

PMID- 27703194
TI  - Maternal Fructose Exposure Programs Metabolic Syndrome-Associated Bladder
      Overactivity in Young Adult Offspring.
AB  - Maternal fructose exposure (MFE) programs the development of metabolic syndrome
      (MetS) in young adult offspring. Epidemiological data indicate that MetS may
      increase the risks of overactive bladder (OAB) symptoms. However, it remains
      unknown whether MFE programs MetS-associated bladder dysfunction in adult
      offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during
      pregnancy and lactation on developmental programming of MetS-associated bladder
      dysfunction. In addition, next generation sequencing technology was used to
      identify potential transcripts involved in the programmed bladder dysfunction in
      adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB
      symptoms (i.e., an increase in micturition frequency and a shortened mean inter
      contractile interval) in young adult male offspring, alongside significant
      alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and
      Vipr2 gene expression. At protein level, the expressions of M2-, M3-muscarinic
      and P2X1 receptor proteins were upregulated in the MFE bladder. Functionally, the
      carbachol-induced detrusor contractility was reduced in the MFE offspring. These
      data suggest that alterations in the bladder transcripts and impairment of the
      bladder cholinergic pathways may underlie the pathophysiology of programmed
      bladder dysfunction in adult offspring to MFE.

PMID- 27703195
TI  - Dual-responsive and Multi-functional Plasmonic Hydrogel Valves and Biomimetic
      Architectures Formed with Hydrogel and Gold Nanocolloids.
AB  - We present a straightforward approach with high moldability for producing dual
      responsive and multi-functional plasmonic hydrogel valves and biomimetic
      architectures that reversibly change volumes and colors in response to
      temperature and ion variations. Heating of a mixture of hybrid colloids (gold
      nanoparticles assembled on a hydrogel colloid) and hydrogel colloids rapidly
      induces (within 30 min) the formation of hydrogel architectures resembling mold
      shapes (cylinder, fish, butterfly). The biomimetic fish and butterfly display
      reversible changes in volumes and colors with variations of temperature and ionic
      conditions in aqueous solutions. The cylindrical plasmonic valves installed in
      flow tubes rapidly control water flow rate in on-off manner by responding to
      these stimuli. They also report these changes in terms of their colors.
      Therefore, the approach presented here might be helpful in developing new class
      of biomimetic and flow control systems where liquid conditions should be visually
      notified (e.g., glucose or ion concentration changes).

PMID- 27703196
TI  - Degradation of Redox-Sensitive Proteins including Peroxiredoxins and DJ-1 is
      Promoted by Oxidation-induced Conformational Changes and Ubiquitination.
AB  - Reactive oxygen species (ROS) are key molecules regulating various cellular
      processes. However, what the cellular targets of ROS are and how their functions
      are regulated is unclear. This study explored the cellular proteomic changes in
      response to oxidative stress using H2O2 in dose- and recovery time-dependent
      ways. We found discernible changes in 76 proteins appearing as 103 spots on 2D
      PAGE. Of these, Prxs, DJ-1, UCH-L3 and Rla0 are readily oxidized in response to
      mild H2O2 stress, and then degraded and active proteins are newly synthesized
      during recovery. In studies designed to understand the degradation process,
      multiple cellular modifications of redox-sensitive proteins were identified by
      peptide sequencing with nanoUPLC-ESI-q-TOF tandem mass spectrometry and the
      oxidative structural changes of Prx2 explored employing hydrogen/deuterium
      exchange-mass spectrometry (HDX-MS). We found that hydrogen/deuterium exchange
      rate increased in C-terminal region of oxidized Prx2, suggesting the exposure of
      this region to solvent under oxidation. We also found that Lys191 residue in this
      exposed C-terminal region of oxidized Prx2 is polyubiquitinated and the
      ubiquitinated Prx2 is readily degraded in proteasome and autophagy. These
      findings suggest that oxidation-induced ubiquitination and degradation can be a
      quality control mechanism of oxidized redox-sensitive proteins including Prxs and
      DJ-1.

PMID- 27703198
TI  - Undermining and Strengthening Social Networks through Network Modification.
AB  - Social networks have well documented effects at the individual and aggregate
      level. Consequently it is often useful to understand how an attempt to influence
      a network will change its structure and consequently achieve other goals. We
      develop a framework for network modification that allows for arbitrary objective
      functions, types of modification (e.g. edge weight addition, edge weight removal,
      node removal, and covariate value change), and recovery mechanisms (i.e. how a
      network responds to interventions). The framework outlined in this paper helps
      both to situate the existing work on network interventions but also opens up many
      new possibilities for intervening in networks. In particular use two case studies
      to highlight the potential impact of empirically calibrating the objective
      function and network recovery mechanisms as well as showing how interventions
      beyond node removal can be optimised. First, we simulate an optimal removal of
      nodes from the Noordin terrorist network in order to reduce the expected number
      of attacks (based on empirically predicting the terrorist collaboration network
      from multiple types of network ties). Second, we simulate optimally strengthening
      ties within entrepreneurial ecosystems in six developing countries. In both cases
      we estimate ERGM models to simulate how a network will endogenously evolve after
      intervention.

PMID- 27703197
TI  - COMPASS: A computational model to predict changes in MMSE scores 24-months after
      initial assessment of Alzheimer's disease.
AB  - We present COMPASS, a COmputational Model to Predict the development of
      Alzheimer's diSease Spectrum, to model Alzheimer's disease (AD) progression. This
      was the best-performing method in recent crowdsourcing benchmark study, DREAM
      Alzheimer's Disease Big Data challenge to predict changes in Mini-Mental State
      Examination (MMSE) scores over 24-months using standardized data. In the present
      study, we conducted three additional analyses beyond the DREAM challenge question
      to improve the clinical contribution of our approach, including: (1) adding pre
      validated baseline cognitive composite scores of ADNI-MEM and ADNI-EF, (2)
      identifying subjects with significant declines in MMSE scores, and (3)
      incorporating SNPs of top 10 genes connected to APOE identified from functional
      relationship network. For (1) above, we significantly improved predictive
      accuracy, especially for the Mild Cognitive Impairment (MCI) group. For (2), we
      achieved an area under ROC of 0.814 in predicting significant MMSE decline: our
      model has 100% precision at 5% recall, and 91% accuracy at 10% recall. For (3),
      "genetic only" model has Pearson's correlation of 0.15 to predict progression in
      the MCI group. Even though addition of this limited genetic model to COMPASS did
      not improve prediction of progression of MCI group, the predictive ability of SNP
      information extended beyond well-known APOE allele.

PMID- 27703199
TI  - l-Ornithine affects peripheral clock gene expression in mice.
AB  - The peripheral circadian clock is entrained by factors in the external
      environment such as scheduled feeding, exercise, and mental and physical
      stresses. In addition, recent studies in mice demonstrated that some food
      components have the potential to control the peripheral circadian clock during
      scheduled feeding, although information about these components remains limited. l
      Ornithine is a type of non-protein amino acid that is present in foods and has
      been reported to have various physiological functions. In human trials, for
      example, l-ornithine intake improved a subjective index of sleep quality. Here we
      demonstrate, using an in vivo monitoring system, that repeated oral
      administration of l-ornithine at an early inactive period in mice induced a phase
      advance in the rhythm of PER2 expression. By contrast, l-ornithine administration
      to mouse embryonic fibroblasts did not affect the expression of PER2, indicating
      that l-ornithine indirectly alters the phase of PER2. l-Ornithine also increased
      plasma levels of insulin, glucose and glucagon-like peptide-1 alongside mPer2
      expression, suggesting that it exerts its effects probably via insulin secretion.
      Collectively, these findings demonstrate that l-ornithine affects peripheral
      clock gene expression and may expand the possibilities of L-ornithine as a health
      food.

PMID- 27703200
TI  - Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung
      injury.
AB  - Although pneumococcal infection is a serious problem worldwide and has a high
      mortality rate, the molecular mechanisms underlying the lethality caused by
      pneumococcus remain elusive. Here, we show that BLT2, a G protein-coupled
      receptor for leukotriene B4 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT),
      protects mice from lung injury caused by a pneumococcal toxin, pneumolysin (PLY).
      Intratracheal injection of PLY caused lethal acute lung injury (ALI) in BLT2
      deficient mice, with evident vascular leakage and bronchoconstriction. Large
      amounts of cysteinyl leukotrienes (cysLTs), classically known as a slow reactive
      substance of anaphylaxis, were detected in PLY-treated lungs. PLY-dependent
      vascular leakage, bronchoconstriction, and death were markedly ameliorated by
      treatment with a CysLT1 receptor antagonist. Upon stimulation by PLY, mast cells
      produced cysLTs that activated CysLT1 expressed in vascular endothelial cells and
      bronchial smooth muscle cells, leading to lethal vascular leakage and
      bronchoconstriction. Treatment of mice with aspirin or loxoprofen inhibited the
      production of 12-HHT and increased the sensitivity toward PLY, which was also
      ameliorated by the CysLT1 antagonist. Thus, the present study identifies the
      molecular mechanism underlying PLY-dependent ALI and suggests the possible use of
      CysLT1 antagonists as a therapeutic tool to protect against ALI caused by
      pneumococcal infection.

PMID- 27703202
TI  - Inflammatory markers and clinical characteristics for predicting persistent
      positivity of interferon gamma release assay in dialysis population.
AB  - The interferon-gamma release assay (IGRA) is useful for diagnosing latent
      tuberculosis infection (LTBI), however the rate of negative conversion is high,
      especially in dialysis patients. Few studies have focused on predicting
      persistently positive patients who are at high risk of tuberculosis reactivation.
      We screened dialysis patients, and used QuantiFERON-TB Gold In-tube (QFT-GIT) to
      identify LTBI. Of the 157 participants who had initially positive QFT-GIT, 82 had
      persistently positivity and 75 had negative conversion. The persistently positive
      group were younger, more were current smokers, and had higher plasma level of
      soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and QFT-GIT
      responses than the negative conversion group. Multivariate logistic regression
      for persistent positivity revealed that high plasma sTREM-1 and QFT-GIT response,
      young age and TB contact history were independent factors. Currently smoking had
      borderline significance. The area under the receiver operating characteristic
      curve using the multi-factor model was 0.878, higher than 0.821 by QFT-GIT
      response of 0.95 IU/ml. In conclusion, dialysis patients with persistent LTBI
      status may be associated with a young age, high plasma sTREM-1, strong QFT-GIT
      response, currently smoking, and TB contact history. If resources are limited,
      these five predictors can be used to prioritize QFT-GIT-positive dialysis
      patients for LTBI treatment.

PMID- 27703203
TI  - Unravelling the low-temperature metastable state in perovskite solar cells by
      noise spectroscopy.
AB  - The hybrid perovskite methylammonium lead iodide CH3NH3PbI3 recently revealed its
      potential for the manufacturing of low-cost and efficient photovoltaic cells.
      However, many questions remain unanswered regarding the physics of the charge
      carrier conduction. In this respect, it is known that two structural phase
      transitions, occurring at temperatures near 160 and 310 K, could profoundly
      change the electronic properties of the photovoltaic material, but, up to now, a
      clear experimental evidence has not been reported. In order to shed light on this
      topic, the low-temperature phase transition of perovskite solar cells has been
      thoroughly investigated by using electric noise spectroscopy. Here it is shown
      that the dynamics of fluctuations detect the existence of a metastable state in a
      crossover region between the room-temperature tetragonal and the low-temperature
      orthorhombic phases of the perovskite compound. Besides the presence of a noise
      peak at this transition, a saturation of the fluctuation amplitudes is observed
      induced by the external DC current or, equivalently, by light exposure. This
      noise saturation effect is independent on temperature, and may represent an
      important aspect to consider for a detailed explanation of the mechanisms of
      operation in perovskite solar cells.

PMID- 27703201
TI  - Rhein reversal of DNA hypermethylation-associated Klotho suppression ameliorates
      renal fibrosis in mice.
AB  - Renal fibrosis is the hallmark of chronic kidney diseases (CKD) and its
      development and progression are significantly affected by epigenetic
      modifications. Rhein, a plant-derived anthraquinone, displays strong anti
      fibrosis properties, but its protective mode of action remains incompletely
      understood. Here we explore the mechanism of Rhein anti-renal fibrosis by
      investigating its regulation of Klotho, a known renal anti-fibrotic protein whose
      suppression after renal injury reportedly involves aberrant DNA methylation. We
      report that Rhein is an impressive up-regulator of Klotho and it markedly
      reversed Klotho down-regulation in unilateral ureteral occlusion-induced fibrotic
      kidney. Further examinations revealed that Klotho loss in fibrotic kidney is
      associated with Klotho promoter hypermethylation due to aberrant
      methyltransferase 1 and 3a expressions. However, Rhein significantly corrected
      all these epigenetic alterations and subsequently alleviated pro-fibrotic protein
      expression and renal fibrosis, whereas Klotho knockdown via RNA interferences
      largely abrogated the anti-renal fibrotic effects of Rhein, suggesting that Rhein
      epigenetic reversal of Klotho loss represents a critical mode of action that
      confers Rhein's anti- renal fibrotic functions. Altogether our studies uncover a
      novel hypomethylating character of Rhein in preventing Klotho loss and renal
      fibrosis, and demonstrate the efficacy of Klotho-targeted epigenetic intervention
      in potential treatment of renal fibrosis-associated kidney diseases.

PMID- 27703204
TI  - Laser-assisted fabrication of single-layer flexible touch sensor.
AB  - Single-layer flexible touch sensor that is designed for the indium-tin-oxide
      (ITO)-free, bendable, durable, multi-sensible, and single layer transparent touch
      sensor was developed via a low-cost and one-step laser-induced fabrication
      technology. To this end, an entirely novel approach involving material, device
      structure, and even fabrication method was adopted. Conventional metal oxides
      based multilayer touch structure was substituted by the single layer structure
      composed of integrated silver wire networks of sensors and bezel
      interconnections. This structure is concurrently fabricated on a glass
      substitutive plastic film via the laser-induced fabrication method using the low
      cost organometallic/nanoparticle hybrid complex. In addition, this study
      addresses practical solutions to heterochromia and interference problem with a
      color display unit. As a result, a practical touch sensor is successfully
      demonstrated through resolving the heterochromia and interference problems with
      color display unit. This study could provide the breakthrough for early
      realization of wearable device.

PMID- 27703205
TI  - Effects of Resistance-Associated NS5A Mutations in Hepatitis C Virus on Viral
      Production and Susceptibility to Antiviral Reagents.
AB  - Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have potent anti-HCV
      effects but may provoke resistance-associated variants (RAVs). In this study, we
      assessed the characteristics of these RAVs and explored efficacious anti-HCV
      reagents using recombinant HCV with NS5A from a genotype 1b strain. We replaced
      the NS5A of JFH1 with that of Con1 (JFH1/5ACon1) and introduced known NS5A
      inhibitor resistance mutations (L31M, L31V, L31I and Y93H) individually or in
      combination. Susceptibilities against anti-HCV reagents were also investigated.
      RAVs with Y93H exhibited high extracellular core antigen levels and infectivity
      titers. Variants with any single mutation showed mild to moderate resistance
      against NS5A inhibitors, whereas variants with double mutations at both L31 and
      Y93 showed severe resistance. The variants with mutations exhibited similar
      levels of susceptibility to interferon (IFN)-alpha, IFN-lambda1, IFN-lambda3 and
      Ribavirin. Variants with the Y93H mutation were more sensitive to protease
      inhibitors compared with JFH1/5ACon1. In conclusion, the in vitro analysis
      indicated that the Y93H mutation enhanced infectious virus production, suggesting
      advantages in the propagation of RAVs with this mutation. However, these RAVs
      were susceptible to protease inhibitors. Thus, a therapeutic regimen that
      includes these reagents is a promising means to eradicate these RAVs.

PMID- 27703206
TI  - Two isoforms of TALDO1 generated by alternative translational initiation show
      differential nucleocytoplasmic distribution to regulate the global metabolic
      network.
AB  - Transaldolase 1 (TALDO1) is a rate-limiting enzyme involved in the pentose
      phosphate pathway, which is traditionally thought to occur in the cytoplasm. In
      this study, we found that the gene TALDO1 has two translational initiation sites,
      generating two isoforms that differ by the presence of the first 10 N-terminal
      amino acids. Notably, the long and short isoforms were differentially localised
      to the cell nucleus and cytoplasm, respectively. Pull-down and in vitro transport
      assays showed that the long isoform, unlike the short one, binds to importin
      alpha and is actively transported into the nucleus in an importin alpha/beta
      dependent manner, demonstrating that the 10 N-terminal amino acids are essential
      for its nuclear localisation. Additionally, we found that these two isoforms can
      form homo- and/or hetero-dimers with different localisation dynamics. A
      metabolite analysis revealed that the subcellular localisation of TALDO1 is not
      crucial for its activity in the pentose phosphate pathway. However, the
      expression of these two isoforms differentially affected the levels of various
      metabolites, including components of the tricarboxylic acid cycle, nucleotides,
      and sugars. These results demonstrate that the nucleocytoplasmic distribution of
      TALDO1, modulated via alternative translational initiation and dimer formation,
      plays an important role in a wide range of metabolic networks.

PMID- 27703208
TI  - Corrigendum: A load of mice to hypergravity causes AMPKalpha repression with
      liver injury, which is overcome by preconditioning loads via Nrf2.

PMID- 27703207
TI  - Novel population of small tumour-initiating stem cells in the ovaries of women
      with borderline ovarian cancer.
AB  - Small stem cells with diameters of up to 5 MUm previously isolated from adult
      human ovaries indicated pluripotency and germinal lineage, especially primordial
      germ cells, and developed into primitive oocyte-like cells in vitro. Here, we
      show that a comparable population of small stem cells can be found in the ovarian
      tissue of women with borderline ovarian cancer, which, in contrast to small stem
      cells in "healthy" ovaries, formed spontaneous tumour-like structures and
      expressed some markers related to pluripotency and germinal lineage. The gene
      expression profile of these small putative cancer stem cells differed from
      similar cells sorted from "healthy" ovaries by 132 upregulated and 97
      downregulated genes, including some important forkhead box and homeobox genes
      related to transcription regulation, developmental processes, embryogenesis, and
      ovarian cancer. These putative cancer stem cells are suggested to be a novel
      population of ovarian tumour-initiating cells in humans.

PMID- 27703209
TI  - A novel exopolysaccharide elicitor from endophytic fungus Gilmaniella sp. AL12 on
      volatile oils accumulation in Atractylodes lancea.
AB  - Endophytes and plants can establish specific long-term symbiosis through the
      accumulation of secondary metabolites. Previous studies have shown that the
      endophytic fungus Gilmaniella sp. AL12 can stimulate Atractylodes lancea to
      produce volatile oils. The purpose of this report is to investigate key factors
      involved in the stimulation of A. lancea by AL12 and reveal the mechanism. We
      identified the active component from AL12 as an extracellular mannan with a
      polymerization degree of 26-42. Differential membrane proteomics of A. lancea was
      performed by 2D electrophoresis. The results showed that there were significant
      differences in the expression of 83 proteins. Based on these results, we conclude
      that AL12 secreted mannan contributes to the antagonistic balance seen in
      interactions between AL12 and A. lancea. One portion of the mannan was degraded
      to mannose for hexokinase activation, promoting photosynthesis and energy
      metabolism, with a potential metabolic fluxes flowing towards terpenoid
      biosynthesis. The other portion of the mannan directly enhanced autoimmunity of
      A. lancea through G protein-mediated signal transduction and the mannan-binding
      lectin pathway. Volatile oil accumulation was ultimately promoted in subsequent
      defense reactions. This study provides a new perspective on the regulation of
      secondary metabolites by endophytic fungal elicitors in medicinal plants.

PMID- 27703210
TI  - Preparation of cross-linked hen-egg white lysozyme crystals free of cracks.
AB  - Cross-linked protein crystals (CLPCs) are very useful materials in applications
      such as biosensors, catalysis, and X-ray crystallography. Hence, preparation of
      CLPCs is an important research direction. During the preparation of CLPCs, an
      often encountered problem is that cracks may appear in the crystals, which may
      finally lead to shattering of the crystals into small pieces and cause problem in
      practical applications. To avoid cross-link induced cracking, it is necessary to
      study the cracking phenomenon in the preparation process. In this paper, we
      present an investigation on how to avoid cracking during preparation of CLPCs. An
      orthogonal experiment was designed to study the phenomenon of cross-link induced
      cracking of hen-egg white lysozyme (HEWL) crystals against five parameters
      (temperature, solution pH, crystal growth time, glutaraldehyde concentration, and
      cross-linking time). The experimental results showed that, the solution pH and
      crystal growth time can significantly affect cross-link induced cracking. The
      possible mechanism was studied, and optimized conditions for obtaining crack-free
      CLPCs were obtained and experimentally verified.

PMID- 27703212
TI  - Construction of CuS/Au Heterostructure through a Simple Photoreduction Route for
      Enhanced Electrochemical Hydrogen Evolution and Photocatalysis.
AB  - An efficient Hydrogen evolution catalyst has been developed by decorating Au
      nanoparticle on the surface of CuS nanostructure following a green and
      environmental friendly approach. CuS nanostructure is synthesized through a
      simple wet-chemical route. CuS being a visible light photocatalyst is introduced
      to function as an efficient reducing agent. Photogenerated electron is used to
      reduce Au(III) on the surface of CuS to prepare CuS/Au heterostructure. The as
      obtained heterostructure shows excellent performance in electrochemical H2
      evolution reaction with promising durability in acidic condition, which could
      work as an efficient alternative for novel metals. The most efficient CuS-Au
      heterostructure can generate 10 mA/cm2 current density upon application of 0.179
      V vs. RHE. CuS-Au heterostructure can also perform as an efficient photocatalyst
      for the degradation of organic pollutant. This dual nature of CuS and CuS/Au both
      in electrocatalysis and photocatalysis has been unveiled in this study.

PMID- 27703211
TI  - Fractionated radiation exposure amplifies the radioresistant nature of prostate
      cancer cells.
AB  - The risk of recurrence following radiation therapy remains high for a significant
      number of prostate cancer patients. The development of in vitro isogenic models
      of radioresistance through exposure to fractionated radiation is an increasingly
      used approach to investigate the mechanisms of radioresistance in cancer cells
      and help guide improvements in radiotherapy standards. We treated 22Rv1 prostate
      cancer cells with fractionated 2 Gy radiation to a cumulative total dose of 60
      Gy. This process selected for 22Rv1-cells with increased clonogenic survival
      following subsequent radiation exposure but increased sensitivity to Docetaxel.
      This RR-22Rv1 cell line was enriched in S-phase cells, less susceptible to DNA
      damage, radiation-induced apoptosis and acquired enhanced migration potential,
      when compared to wild type and aged matched control 22Rv1 cells. The selection of
      radioresistant cancer cells during fractionated radiation therapy may have
      implications in the development and administration of future targeted therapy in
      conjunction with radiation therapy.

PMID- 27703213
TI  - Bone marrow mesenchymal stem cells attenuate 2,5-hexanedione-induced neuronal
      apoptosis through a NGF/AKT-dependent pathway.
AB  - Growing evidence suggests that the increased neuronal apoptosis is involved in n
      hexane-induced neuropathy. We have recently reported that bone marrow-mesenchymal
      stem cells-derived conditioned medium (BMSC-CM) attenuated 2,5-hexanedione (HD,
      the active metabolite of n-hexane)-induced apoptosis in PC12 cells. Here, we
      explored the anti-apoptotic efficacy of BMSC in vivo. HD-treated rats received
      BMSC by tail vein injection 5 weeks after HD intoxication. We found that in
      grafted rats, BMSC significantly attenuated HD-induced neuronal apoptosis in the
      spinal cord, which was associated with elevation of nerve growth factor (NGF).
      Neutralization of NGF in BMSC-CM blocked the protection against HD-induced
      apoptosis in VSC4.1 cells, suggesting that NGF is essential for BMSC-afforded
      anti-apoptosis. Mechanistically, we found that the decreased activation of Akt
      induced by HD was significantly recovered in the spinal cord by BMSC and in
      VSC4.1 cells by BMSC-CM in a TrkA-dependent manner, leading to dissociation of
      Bad/Bcl-xL complex in mitochondria and release of anti-apoptotic Bcl-xL. The
      importance of Akt was further corroborated by showing the reduced anti-apoptotic
      potency of BMSC in HD-intoxicated VSC4.1 cells in the presence of Akt inhibitor,
      MK-2206. Thus, our findings show that BMSC attenuated HD-induced neuronal
      apoptosis in vivo through a NGF/Akt-dependent manner, providing a novel solution
      against n-hexane-induced neurotoxicity.

PMID- 27703214
TI  - Lateralization of gene expression in the honeybee brain during olfactory
      learning.
AB  - In the last decade, it has been demonstrated that brain functional asymmetry
      occurs not only in vertebrates but also in invertebrates. However, the mechanisms
      underlying functional asymmetry remain unclear. In the present study, we trained
      honeybees of the same parentage and age, on the proboscis extension reflex (PER)
      paradigm with only one antenna in use. The comparisons of gene expression between
      the left and right hemispheres were carried out using high throughput sequencing.
      Our research revealed that gene expression in the honeybee brain is also
      asymmetric, with more genes having higher expression in the right hemisphere than
      the left hemisphere. Our studies show that during olfactory learning, the left
      hemisphere is more responsible for long term memory and the right hemisphere is
      more responsible for the learning and short term memory.

PMID- 27703215
TI  - Forest biomass carbon stocks and variation in Tibet's carbon-dense forests from
      2001 to 2050.
AB  - Tibet's forests, in contrast to China's other forests, are characterized by
      primary forests, high carbon (C) density and less anthropogenic disturbance, and
      they function as an important carbon pool in China. Using the biomass C density
      data from 413 forest inventory sites and a spatial forest age map, we developed
      an allometric equation for the forest biomass C density and forest age to assess
      the spatial biomass C stocks and variation in Tibet's forests from 2001 to 2050.
      The results indicated that the forest biomass C stock would increase from 831.1
      Tg C in 2001 to 969.4 Tg C in 2050, with a net C gain of 3.6 Tg C yr-1 between
      2001 and 2010 and a decrease of 1.9 Tg C yr-1 between 2040 and 2050. Carbon tends
      to allocate more in the roots of fir forests and less in the roots of spruce and
      pine forests with increasing stand age. The increase of the biomass carbon pool
      does not promote significant augmentation of the soil carbon pool. Our findings
      suggest that Tibet's mature forests will remain a persistent C sink until 2050.
      However, afforestation or reforestation, especially with the larger carbon sink
      potential forest types, such as fir and spruce, should be carried out to maintain
      the high C sink capacity.

PMID- 27703217
TI  - Re-evaluation of all-plastic organic dye laser with DFB structure fabricated
      using photoresists.
AB  - Organic solid-state lasers (OSSLs) with distributed feedback structures can
      detect nanoscale materials and therefore offer an attractive sensing platform for
      biological and medical applications. Here we investigate the lasing
      characteristics, i.e., the threshold and slope efficiency, as a function of the
      grating depth in OSSL devices with distributed feedback (DFB) structure
      fabricated using photoresists. Two types of photoresists were used for the DFB
      structures: a negative photoresist, SU-8 2002, and a positive photoresist, ma-P
      1275. The DFB structure was fabricated using a Lloyd-mirror configuration. The
      active layer was a rhodamine 6G-doped cellulose acetate waveguide. The threshold
      for the first order mode (m  = 1) was lower than that for the second and third
      order modes (m = 2, and 3). A low threshold of 27 MUJ cm-2 pulse-1 (58 nJ) was
      obtained using SU-8 2002, with m = 1. The slope efficiency was evaluated as a
      function of grating depth for each mode and increased as the grating depth
      increased.

PMID- 27703218
TI  - Generation of Scratches and Their Effects on Laser Damage Performance of Silica
      Glass.
AB  - Scratches are deleterious to precision optics because they can obscure and
      modulate incident laser light, which will increase the probability of damage to
      optical components. We here imitated the generation of brittle and ductile
      scratches during polishing process and endeavored to find out the possible
      influence of scratches on laser induced damage. Brittle scratches can be induced
      by spiking large sized abrasives and small abrasives may only generate ductile
      scratches. Both surface roughness and transmittivity are degraded due to the
      appearance of brittle scratches while ductile scratches make little difference to
      surface roughness and transmittance. However, ductile and brittle scratches
      greatly increase the density of damage about one order of magnitude relative to
      unscratched surface. In particular, ductile scratches also play an unignorable
      role in laser induced damage, which is different from previous knowledge.
      Furthermore, ZrO2 and Al2O3 polished surfaces appear to perform best in terms of
      damage density.

PMID- 27703216
TI  - Neocortical grey matter distribution underlying voluntary, flexible vocalizations
      in chimpanzees.
AB  - Vocal learning is a key property of spoken language, which might also be present
      in nonhuman primate species, such as chimpanzees (Pan troglodytes), to a limited
      degree. While understanding the origins of vocal learning in the primate brain
      may help shed light on the evolution of speech and language, little is still
      known regarding the neurobiological correlates of vocal flexibility in nonhuman
      primates. The current study used voxel-based morphometry (VBM) to assess whether
      the cerebral cortex of captive chimpanzees that learned to voluntarily produce
      sounds to attract the attention of a human experimenter (attention-getting
      sounds) differs in grey matter distribution compared to chimpanzees that do not
      exhibit this behavior. It was found that chimpanzees that produce attention
      getting sounds were characterized by increased grey matter in the ventrolateral
      prefrontal and dorsal premotor cortices. These findings suggest that the
      evolution of the capacity to flexibly modulate vocal output may be associated
      with reorganization of regions for motor control, including orofacial movements,
      in the primate brain.

PMID- 27703220
TI  - Nano-volcanic Eruption of Silver.
AB  - Silver (Ag) is one of the seven metals of antiquity and an important engineering
      material in the electronic, medical, and chemical industries because of its
      unique noble and catalytic properties. Ag thin films are extensively used in
      modern electronics primarily because of their oxidation-resistance. Here we
      report a novel phenomenon of Ag nano-volcanic eruption that is caused by
      interactions between Ag and oxygen (O). It involves grain boundary liquation, the
      ejection of transient Ag-O fluids through grain boundaries, and the decomposition
      of Ag-O fluids into O2 gas and suspended Ag and Ag2O clusters. Subsequent coating
      with re-deposited Ag-O and the de-alloying of O yield a conformal amorphous Ag
      coating. Patterned Ag hillock arrays and direct Ag-to-Ag bonding can be formed by
      the homogenous crystallization of amorphous coatings. The Ag "nano-volcanic
      eruption" mechanism is elaborated, shedding light on a new mechanism of hillock
      formation and new applications of amorphous Ag coatings.

PMID- 27703219
TI  - Antiangiogenic therapy using endostatin increases the number of ALDH+ lung cancer
      stem cells by generating intratumor hypoxia.
AB  - Antiangiogenic therapy is becoming a promising option for cancer treatment.
      However, many investigations have recently indicated that these therapies may
      have limited efficacy, and the cancers in most patients eventually develop
      resistance to these therapies. There is considerable recently acquired evidence
      for an association of such resistance with cancer stem-like cells (CSLCs). Here,
      we used xenograft tumor murine models to further suggest that antiangiogenic
      agents actually increase the invasive and metastatic properties of lung cancer
      cells. In our experiments with murine lung cancer xenografts, we found that the
      antiangiogenic agent endostatin increased the population of ALDH+ cells, and did
      so by generating intratumoral hypoxia in the xenografts. We further showed
      endostatin to cause an increase in the CSLC population by accelerating the
      generation of tumor hypoxia and by recruiting TAMs, MDSCs and Treg cells, which
      are inflammatory and immunosuppressive cells and which can secrete cytokines and
      growth factors such as IL-6, EGF, and TGF-beta into the tumor microenvironment.
      All these factors are related with increased CSLC population in tumors. These
      results imply that improving the clinical efficacy of antiangiogenic treatments
      will require the concurrent use of CSLC-targeting agents.

PMID- 27703221
TI  - The Principles of Ligand Specificity on beta-2-adrenergic receptor.
AB  - G protein-coupled receptors are recognized as one of the largest families of
      membrane proteins. Despite sharing a characteristic seven-transmembrane topology,
      G protein-coupled receptors regulate a wide range of cellular signaling pathways
      in response to various physical and chemical stimuli, and prevail as an important
      target for drug discovery. Notably, the recent progress in crystallographic
      methods led to a breakthrough in elucidating the structures of membrane proteins.
      The structures of beta2-adrenergic receptor bound with a variety of ligands
      provide atomic details of the binding modes of agonists, antagonists and inverse
      agonists. In this study, we selected four representative molecules from each
      functional class of ligands and investigated their impacts on beta2-adrenergic
      receptor through a total of 12 * 100 ns molecular dynamics simulations. From the
      obtained trajectories, we generated molecular fingerprints exemplifying
      propensities of protein-ligand interactions. For each functional class of
      compounds, we characterized and compared the fluctuation of the protein backbone,
      the volumes in the intracellular pockets, the water densities in the receptors,
      the domain interaction networks as well as the movements of transmembrane
      helices. We discovered that each class of ligands exhibits a distinct mode of
      interactions with mainly TM5 and TM6, altering the shape and eventually the state
      of the receptor. Our findings provide insightful prospective into GPCR targeted
      structure-based drug discoveries.

PMID- 27703222
TI  - Large linear magnetoresistance in heavily-doped Nb:SrTiO3 epitaxial thin films.
AB  - Interaction between electrons has long been a focused topic in condensed-matter
      physics since it has led to the discoveries of astonishing phenomena, for
      example, high-Tc superconductivity and colossal magnetoresistance (CMR) in
      strongly-correlated materials. In the study of strongly-correlated perovskite
      oxides, Nb-doped SrTiO3 (Nb:SrTiO3) has been a workhorse not only as a conducting
      substrate, but also as a host possessing high carrier mobility. In this work, we
      report the observations of large linear magnetoresistance (LMR) and the metal-to
      insulator transition (MIT) induced by magnetic field in heavily-doped Nb:STO
      (SrNb0.2Ti0.8O3) epitaxial thin films. These phenomena are associated with the
      interplay between the large classical MR due to high carrier mobility and the
      electronic localization effect due to strong spin-orbit coupling, implying that
      heavily Nb-doped Sr(Nb0.2Ti0.8)O3 is promising for the application in spintronic
      devices.

PMID- 27703223
TI  - Directional and monochromatic thermal emitter from epsilon-near-zero conditions
      in semiconductor hyperbolic metamaterials.
AB  - The development of novel thermal sources that control the emission spectrum and
      the angular emission pattern is of fundamental importance. In this paper, we
      investigate the thermal emission properties of semiconductor hyperbolic
      metamaterials (SHMs). Our structure does not require the use of any periodic
      corrugation to provide monochromatic and directional emission properties. We show
      that these properties arise because of epsilon-near-zero conditions in SHMs. The
      thermal emission is dominated by the epsilon-near-zero effect in the doped
      quantum wells composing the SHM. Furthermore, different properties are observed
      for s and p polarizations, following the characteristics of the strong anisotropy
      of hyperbolic metamaterials.

PMID- 27703226
TI  - Hybrid boron nitride-natural fiber composites for enhanced thermal conductivity.
AB  - Thermal conductivity was dramatically increased after adding natural fiber into
      hexagonal boron nitride (hBN)/epoxy composites. Although natural fiber does not
      show high-thermal conductivity itself, this study found that the synergy of
      natural fiber with hBN could significantly improve thermal conductivity, compared
      with that solely using hBN. A design of mixtures approach using constant fibers
      with increasing volume fractions of hBN was examined and compared. The thermal
      conductivity of the composite containing 43.6% hBN, 26.3% kenaf fiber and 30.1%
      epoxy reached 6.418 W m-1 K-1, which was 72.3% higher than that (3.600 W m-1 K-1)
      of the 69.0% hBN and 31.0% epoxy composite. Using the scanning electron
      microscope (SEM) and micro computed tomography (micro-CT), it was observed that
      the hBN powders were well distributed and ordered on the fiber surfaces enhancing
      the ceramic filler's interconnection, which may be the reason for the increase in
      thermal conductivity. Additionally, the results from mechanical and dynamic
      mechanical tests showed that performances dramatically improved after adding
      kenaf fibers into the hBN/epoxy composite, potentially benefiting the composite's
      use as an engineered material.

PMID- 27703227
TI  - Pancreatic cancer: Mapping malignant tissue dynamics.

PMID- 27703224
TI  - Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis
      through regulation of JNK2 signaling and Smad3 binding activity.
AB  - Gallic acid, a type of phenolic acid, has been shown to have beneficial effects
      in inflammation, vascular calcification, and metabolic diseases. The present
      study was aimed at determining the effect and regulatory mechanism of gallic acid
      in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by
      isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid
      pretreatment attenuated concentric cardiac hypertrophy. It downregulated the
      expression of atrial natriuretic peptide, brain natriuretic peptide, and beta
      myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial
      collagen deposition and expression of fibrosis-associated genes. Upregulation of
      collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2
      cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding
      activity of phosphorylated Smad3 in Smad binding sites of collagen type I
      promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced
      phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal
      regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type
      I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac
      fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of
      cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling
      pathway.

PMID- 27703228
TI  - IBD: A role for GATA3 in ulcerative colitis.

PMID- 27703225
TI  - Preserved implicit mentalizing in schizophrenia despite poor explicit
      performance: evidence from eye tracking.
AB  - Schizophrenia has been characterized by an impaired mentalizing. It has been
      suggested that distinguishing implicit from explicit processes is crucial in
      social cognition, and only the latter might be affected in schizophrenia. Two
      other questions remain open: (1) Is schizophrenia characterized by an hypo- or
      hyper attribution of intentions? (2) Is it characterized by a deficit in the
      attribution of intention or of contingency? To test these three questions,
      spontaneous mentalizing was tested in 29 individuals with schizophrenia and 29
      control subjects using the Frith-Happe animations, while eye movements were
      recorded. Explicit mentalizing was measured from participants' verbal
      descriptions and was contrasted with implicit mentalizing measured through eye
      tracking. As a group, patients made less accurate and less intentional
      descriptions of the goal-directed and theory of mind animations. No group
      differences were found in the attribution of contingency. Eye tracking results
      revealed that patients and controls showed a similar modulation of eye movements
      in response to the mental states displayed in the Frith-Happe animations. To
      conclude, in this paradigm, participants with schizophrenia showed a dissociation
      between explicit and implicit mentalizing, with a decrease in the explicit
      attribution of intentions, whereas their eye movements suggested a preserved
      implicit perception of intentions.

PMID- 27703229
TI  - The antenna of horse stomach bot flies: morphology and phylogenetic implications
      (Oestridae, Gasterophilinae: Gasterophilus Leach).
AB  - Antennae are among the most elaborate sensory organs in adult flies, and they
      provide rich information for phylogenic studies. The antennae of five out of
      eight species of Gasterophilus Leach (G. haemorrhoidalis (Linnaeus), G.
      intestinalis (De Geer), G. nasalis (Linnaeus), G. nigricornis (Loew) and G.
      pecorum (Fabricius)), were examined using scanning electron microscopy. The
      general morphology, including distribution, type, size, and ultrastructure of
      antennal sensilla were presented, and the definition of auriculate sensilla and
      sensory pits were updated and clarified. Eighteen antennal characters were
      selected to construct the first species-level phylogeny of this genus. The
      monophyly of Gasterophilus was supported by the presence of coeloconic sensilla
      III on the antennal arista. The species-level cladogram showed G. pecorum
      branching off at the base, and the remaining species forming the topology (G.
      intestinalis+ (G. haemorrhoidalis+ (G. nasalis+ G. nigricornis))). Our research
      shows the importance of the antennal ultrastructure as a reliable source for
      phylogenetic analysis.

PMID- 27703230
TI  - Erosion protection conferred by whole human saliva, dialysed saliva, and
      artificial saliva.
AB  - During dental erosion, tooth minerals are dissolved, leading to a softening of
      the surface and consequently to irreversible surface loss. Components from human
      saliva form a pellicle on the tooth surface, providing some protection against
      erosion. To assess the effect of different components and compositions of saliva
      on the protective potential of the pellicle against enamel erosion, we prepared
      four different kinds of saliva: human whole stimulated saliva (HS), artificial
      saliva containing only ions (AS), human saliva dialysed against artificial
      saliva, containing salivary proteins and ions (HS/AS), and human saliva dialysed
      against deionised water, containing only salivary proteins but no ions (HS/DW).
      Enamel specimens underwent four cycles of immersion in either HS, AS, HS/AS,
      HS/DW, or a humid chamber (Ctrl), followed by erosion with citric acid. During
      the cycling process, the surface hardness and the calcium released from the
      surface of the specimens were measured. The different kinds of saliva provided
      different levels of protection, HS/DW exhibiting significantly better protection
      than all the other groups (p < 0.0001). Different components of saliva,
      therefore, have different effects on the protective properties of the pellicle
      and the right proportions of these components in saliva are critical for the
      ability to form a protective pellicle.

PMID- 27703231
TI  - OAHG: an integrated resource for annotating human genes with multi-level
      ontologies.
AB  - OAHG, an integrated resource, aims to establish a comprehensive functional
      annotation resource for human protein-coding genes (PCGs), miRNAs, and lncRNAs by
      multi-level ontologies involving Gene Ontology (GO), Disease Ontology (DO), and
      Human Phenotype Ontology (HPO). Many previous studies have focused on inferring
      putative properties and biological functions of PCGs and non-coding RNA genes
      from different perspectives. During the past several decades, a few of databases
      have been designed to annotate the functions of PCGs, miRNAs, and lncRNAs,
      respectively. A part of functional descriptions in these databases were mapped to
      standardize terminologies, such as GO, which could be helpful to do further
      analysis. Despite these developments, there is no comprehensive resource
      recording the function of these three important types of genes. The current
      version of OAHG, release 1.0 (Jun 2016), integrates three ontologies involving
      GO, DO, and HPO, six gene functional databases and two interaction databases.
      Currently, OAHG contains 1,434,694 entries involving 16,929 PCGs, 637 miRNAs, 193
      lncRNAs, and 24,894 terms of ontologies. During the performance evaluation, OAHG
      shows the consistencies with existing gene interactions and the structure of
      ontology. For example, terms with more similar structure could be associated with
      more associated genes (Pearson correlation gamma2 = 0.2428, p < 2.2e-16).

PMID- 27703232
TI  - Integrated analysis of microRNA and mRNA expression profiles highlights the
      complex and dynamic behavior of toosendanin-induced liver injury in mice.
AB  - Triterpenoid Toosendanin (TSN) exhibits a plenty of pharmacological effects in
      human and great values in agriculture. However, the hepatotoxicity caused by TSN
      or Melia-family plants containing TSN used in traditional Chinese medicine has
      been reported, and the mechanisms of TSN-induced liver injury (TILI) still remain
      largely unknown. In this study, the dose- and time-dependent effects of TSN on
      mice liver were investigated by an integrated microRNA-mRNA approach as well as
      the general toxicological assessments. As the results, the dose- and time
      dependent liver injury and alterations in global microRNA and mRNA expressions
      were detected. Particularly, 9-days 80 mg/kg TSN exposure caused most serious
      liver injury in mice, and the hepatic adaptation to TILI was unexpectedly
      observed after 21-days 80 mg/kg TSN administration. Based on the pathway analysis
      of the intersections between predicted targets of differentially expressed
      microRNAs and differentially expressed mRNAs at three time points, it revealed
      that TILI may be caused by glutathione depletion, mitochondrial dysfunction and
      lipid dysmetabolism, ultimately leading to hepatocytes necrosis in liver, while
      liver regeneration may play an important role in the hepatic adaptation to TILI.
      Our results demonstrated that the integrated microRNA-mRNA approach could provide
      new insight into the complex and dynamic behavior of TILI.

PMID- 27703234
TI  - A comprehensive insight into functional profiles of free-living microbial
      community responses to a toxic Akashiwo sanguinea bloom.
AB  - Phytoplankton blooms are a worldwide problem and can greatly affect ecological
      processes in aquatic systems, but its impacts on the functional potential of
      microbial communities are limited. In this study, a high-throughput microarray
      based technology (GeoChip) was used to profile the functional potential of free
      living microbes from the Xiamen Sea Area in response to a 2011 Akashiwo sanguinea
      bloom. The bloom altered the overall community functional structure. Genes that
      were significantly (p < 0.05) increased during the bloom included carbon
      degradation genes and genes involved in nitrogen (N) and/or phosphorus (P)
      limitation stress. Such significantly changed genes were well explained by chosen
      environmental factors (COD, nitrite-N, nitrate-N, dissolved inorganic phosphorus,
      chlorophyll-a and algal density). Overall results suggested that this bloom might
      enhance the microbial converting of nitrate to N2 and ammonia nitrogen, decrease
      P removal from seawater, activate the glyoxylate cycle, and reduce infection
      activity of bacteriophage. This study presents new information on the
      relationship of algae to other microbes in aquatic systems, and provides new
      insights into our understanding of ecological impacts of phytoplankton blooms.

PMID- 27703233
TI  - Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor
      vasculature permeability.
AB  - Recent advances in the field of nanomedicine have demonstrated that biomimicry
      can further improve targeting properties of current nanotechnologies while
      simultaneously enable carriers with a biological identity to better interact with
      the biological environment. Immune cells for example employ membrane proteins to
      target inflamed vasculature, locally increase vascular permeability, and
      extravasate across inflamed endothelium. Inspired by the physiology of immune
      cells, we recently developed a procedure to transfer leukocyte membranes onto
      nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are
      composed of a surface coating containing multiple receptors that are critical in
      the cross-talk with the endothelium, mediating cellular accumulation in the tumor
      microenvironment while decreasing vascular barrier function. We previously
      demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto
      LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM
      1) on endothelial cells. Herein, we provide a more comprehensive analysis of the
      working mechanism of LLV in vitro in activating this pathway and in vivo in
      enhancing vascular permeability. Our results suggest the biological activity of
      the leukocyte membrane can be retained upon transplant onto NPS and is critical
      in providing the particles with complex biological functions towards tumor
      vasculature.

PMID- 27703235
TI  - Two-dimensional symbiotic solitons and vortices in binary condensates with
      attractive cross-species interaction.
AB  - We consider a two-dimensional (2D) two-component spinor system with cubic
      attraction between the components and intra-species self-repulsion, which may be
      realized in atomic Bose-Einstein condensates, as well as in a quasi-equilibrium
      condensate of microcavity polaritons. Including a 2D spatially periodic
      potential, which is necessary for the stabilization of the system against the
      critical collapse, we use detailed numerical calculations and an analytical
      variational approximation (VA) to predict the existence and stability of several
      types of 2D symbiotic solitons in the spinor system. Stability ranges are found
      for symmetric and asymmetric symbiotic fundamental solitons and vortices,
      including hidden-vorticity (HV) modes, with opposite vorticities in the two
      components. The VA produces exceptionally accurate predictions for the
      fundamental solitons and vortices. The fundamental solitons, both symmetric and
      asymmetric ones, are completely stable, in either case when they exist as gap
      solitons or regular ones. The symmetric and asymmetric vortices are stable if the
      inter-component attraction is stronger than the intra-species repulsion, while
      the HV modes have their stability region in the opposite case.

PMID- 27703237
TI  - Corrigendum: A regulatory loop between miR-132 and miR-125b involved in
      gonadotrope cells desensitization to GnRH.

PMID- 27703236
TI  - Nematodes join the family of chondroitin sulfate-synthesizing organisms:
      Identification of an active chondroitin sulfotransferase in Caenorhabditis
      elegans.
AB  - Proteoglycans are proteins that carry sulfated glycosaminoglycans (GAGs). They
      help form and maintain morphogen gradients, guiding cell migration and
      differentiation during animal development. While no sulfated GAGs have been found
      in marine sponges, chondroitin sulfate (CS) and heparan sulfate (HS) have been
      identified in Cnidarians, Lophotrocozoans and Ecdysozoans. The general view that
      nematodes such as Caenorhabditis elegans, which belong to Ecdysozoa, produce HS
      but only chondroitin without sulfation has therefore been puzzling. We have
      analyzed GAGs in C. elegans using reversed-phase ion-pairing HPLC, mass
      spectrometry and immunohistochemistry. Our analyses included wild type C. elegans
      but also a mutant lacking two HS sulfotransferases (hst-6 hst-2), as we suspected
      that the altered HS structure could boost CS sulfation. We could indeed detect
      sulfated CS in both wild type and mutant nematodes. While 4-O-sulfation of
      galactosamine dominated, we also detected 6-O-sulfated galactosamine residues.
      Finally, we identified the product of the gene C41C4.1 as a C. elegans CS
      sulfotransferase and renamed it chst-1 (CarboHydrate SulfoTransferase) based on
      loss of CS-4-O-sulfation in a C41C4.1 mutant and in vitro sulfotransferase
      activity of recombinant C41C4.1 protein. We conclude that C. elegans indeed
      manufactures CS, making this widely used nematode an interesting model for
      developmental studies involving CS.

PMID- 27703238
TI  - Extracting quantitative information from single-molecule super-resolution imaging
      data with LAMA - LocAlization Microscopy Analyzer.
AB  - Super-resolution fluorescence microscopy revolutionizes cell biology research and
      provides novel insights on how proteins are organized at the nanoscale and in the
      cellular context. In order to extract a maximum of information, specialized tools
      for image analysis are necessary. Here, we introduce the LocAlization Microscopy
      Analyzer (LAMA), a comprehensive software tool that extracts quantitative
      information from single-molecule super-resolution imaging data. LAMA allows
      characterizing cellular structures by their size, shape, intensity, distribution,
      as well as the degree of colocalization with other structures. LAMA is freely
      available, platform-independent and designed to provide direct access to
      individual analysis of super-resolution data.

PMID- 27703241
TI  - Gene expression: Reading protein acetylation.

PMID- 27703240
TI  - Antibody titres and boosting after natural malaria infection in BK-SE36 vaccine
      responders during a follow-up study in Uganda.
AB  - The malaria vaccine BK-SE36 is a recombinant protein (SE36) based on the Honduras
      1 serine repeat antigen-5 of Plasmodium falciparum, adsorbed to aluminium
      hydroxide gel. The phase Ib trial in Uganda demonstrated the safety and
      immunogenicity of BK-SE36. Ancillary analysis in the follow-up study of 6-20 year
      old volunteers suggest significant differences in time to first episodes of
      clinical malaria in vaccinees compared to placebo/control group. Here, we aimed
      to get further insights into the association of anti-SE36 antibody titres and
      natural P. falciparum infection. Children who received BK-SE36 and whose antibody
      titres against SE36 increased by >=1.92-fold after vaccination were categorised
      as responders. Most responders did not have or only had a single episode of
      natural P. falciparum infection. Notably, responders who did not experience
      infection had relatively high anti-SE36 antibody titres post-second vaccination
      compared to those who were infected. The anti-SE36 antibody titres of the
      responders who experienced malaria were boosted after infection and they had
      lower risk of reinfection. These findings show that anti-SE36 antibody titres
      induced by BK-SE36 vaccination offered protection against malaria. The vaccine is
      now being evaluated in a phase Ib trial in children less than 5 years old.

PMID- 27703242
TI  - Origins of mass spectrometry-based proteomics.

PMID- 27703239
TI  - Mechanistic evaluation and transcriptional signature of a glutathione S
      transferase omega 1 inhibitor.
AB  - Glutathione S-transferase omega 1 (GSTO1) is an atypical GST isoform that is
      overexpressed in several cancers and has been implicated in drug resistance.
      Currently, no small-molecule drug targeting GSTO1 is under clinical development.
      Here we show that silencing of GSTO1 with siRNA significantly impairs cancer cell
      viability, validating GSTO1 as a potential new target in oncology. We report on
      the development and characterization of a series of chloroacetamide-containing
      potent GSTO1 inhibitors. Co-crystal structures of GSTO1 with our inhibitors
      demonstrate covalent binding to the active site cysteine. These potent GSTO1
      inhibitors suppress cancer cell growth, enhance the cytotoxic effects of
      cisplatin and inhibit tumour growth in colon cancer models as single agent. Bru
      seq-based transcription profiling unravelled novel roles for GSTO1 in cholesterol
      metabolism, oxidative and endoplasmic stress responses, cytoskeleton and cell
      migration. Our findings demonstrate the therapeutic utility of GSTO1 inhibitors
      as anticancer agents and identify the novel cellular pathways under GSTO1
      regulation in colorectal cancer.

PMID- 27703244
TI  - A success story.

PMID- 27703246
TI  - Ten and counting.

PMID- 27703247
TI  - Ten years in images.

PMID- 27703249
TI  - Anniversary thoughts.

PMID- 27703248
TI  - Nano on reflection.

PMID- 27703243
TI  - Reverse-topology membrane scission by the ESCRT proteins.
AB  - The narrow membrane necks formed during viral, exosomal and intra-endosomal
      budding from membranes, as well as during cytokinesis and related processes, have
      interiors that are contiguous with the cytosol. Severing these necks involves
      action from the opposite face of the membrane as occurs during the well
      characterized formation of coated vesicles. This 'reverse' (or 'inverse')
      topology membrane scission is carried out by the endosomal sorting complex
      required for transport (ESCRT) proteins, which form filaments, flat spirals,
      tubes and conical funnels that are thought to direct membrane remodelling and
      scission. Their assembly, and their disassembly by the ATPase vacuolar protein
      sorting-associated 4 (VPS4) have been intensively studied, but the mechanism of
      scission has been elusive. New insights from cryo-electron microscopy and various
      types of spectroscopy may finally be close to rectifying this situation.

PMID- 27703250
TI  - A novel three-axis cylindrical hohlraum designed for inertial confinement fusion
      ignition.
AB  - A novel ignition hohlraum for indirect-drive inertial confinement fusion is
      proposed, which is named three-axis cylindrical hohlraum (TACH). TACH is a kind
      of 6 laser entrance holes (LEHs) hohlraum, which is orthogonally jointed of three
      cylindrical hohlraums. Laser beams are injected through every entrance hole with
      the same incident angle of 55 degrees . A view-factor simulation result shows
      that the time-varying drive asymmetry of TACH is less than 1.0% in the whole
      drive pulse period without any supplementary technology. Coupling efficiency of
      TACH is close to that of 6 LEHs spherical hohlraum with corresponding size. Its
      plasma-filling time is close to that of typical cylindrical ignition hohlraum.
      Its laser plasma interaction has as low backscattering as the outer cone of the
      cylindrical ignition hohlraum. Therefore, TACH combines most advantages of
      various hohlraums and has little predictable risk, providing an important
      competitive candidate for ignition hohlraum.

PMID- 27703251
TI  - Towards Dynamic Contrast Specific Ultrasound Tomography.
AB  - We report on the first study demonstrating the ability of a recently-developed,
      contrast-enhanced, ultrasound imaging method, referred to as cumulative phase
      delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA)
      kinetics. Unlike standard ultrasound tomography, which exploits changes in speed
      of sound and attenuation, CPDI is based on a marker specific to UCAs, thus
      enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast
      imaging, DCS-UST will lead to a more practical, faster, and less operator
      dependent imaging procedure compared to standard echo-contrast, while preserving
      accurate imaging of contrast kinetics. Moreover, a linear relation between CPD
      values and ultrasound second-harmonic intensity was measured (coefficient of
      determination = 0.87). DCS-UST can find clinical applications as a diagnostic
      method for breast cancer localization, adding important features to multi
      parametric ultrasound tomography of the breast.

PMID- 27703252
TI  - The functional activity and effective connectivity of pulvinar are modulated by
      individual differences in threat-related attentional bias.
AB  - The pulvinar is important in selective attention, particularly to visual stimuli
      under the focus of attention. However, the pulvinar is assumed to process
      emotional stimuli even outside the focus of attention, because of its tight
      connection with the amygdala. We therefore investigated how unattended emotional
      stimuli affect the pulvinar and its effective connectivity (EC) while considering
      individual differences in selective attention. fMRI in 41 healthy human subjects
      revealed that the amygdala, but not the pulvinar, more strongly responded to
      unattended fearful faces than to unattended neutral faces (UF > UN), although we
      observed greater EC from the pulvinar to the amygdala. Interestingly, individuals
      with biased attention toward threat (i.e., attentional bias) showed significantly
      increased activity (UF > UN) and reduced grey matter volume in the pulvinar.
      These individuals also exhibited stronger EC from the pulvinar to the attention
      related frontoparietal network (FPN), whereas individuals with greater
      attentional control showed more enhanced EC from the pulvinar to the amygdala,
      but not the FPN (UF > UN). The pulvinar may filter unattended emotional stimuli
      whose sensitivity depends on individual threat-related attentional bias. The
      connectivity patterns of the pulvinar may thus be determined based on individual
      differences in threat-related attentional bias and attentional control.

PMID- 27703253
TI  - Surface step terrace tuned microstructures and dielectric properties of highly
      epitaxial CaCu3Ti4O12 thin films on vicinal LaAlO3 substrates.
AB  - Controllable interfacial strain can manipulate the physical properties of
      epitaxial films and help understand the physical nature of the correlation
      between the properties and the atomic microstructures. By using a proper design
      of vicinal single-crystal substrate, the interface strain in epitaxial thin films
      can be well controlled by adjusting the miscut angle via a surface-step-terrace
      matching growth mode. Here, we demonstrate that LaAlO3 (LAO) substrates with
      various miscut angles of 1.0 degrees , 2.75 degrees , and 5.0 degrees  were used
      to tune the dielectric properties of epitaxial CaCu3Ti4O12 (CCTO) thin films. A
      model of coexistent compressive and tensile strained domains is proposed to
      understand the epitaxial nature. Our findings on the self-tuning of the
      compressive and tensile strained domain ratio along the interface depending on
      the miscut angle and the stress relaxation mechanism under this growth mode will
      open a new avenue to achieve CCTO films with high dielectric constant and low
      dielectric loss, which is critical for the design and integration of advanced
      heterostructures for high performance capacitance device applications.

PMID- 27703254
TI  - Fully Controllable Pancharatnam-Berry Metasurface Array with High Conversion
      Efficiency and Broad Bandwidth.
AB  - Metasurfaces have powerful abilities to manipulate the properties of
      electromagnetic waves flexibly, especially the modulation of polarization state
      for both linearly polarized (LP) and circularly polarized (CP) waves. However,
      the transmission efficiency of cross-polarization conversion by a single-layer
      metasurface has a low theoretical upper limit of 25% and the bandwidth is usually
      narrow, which cannot be resolved by their simple additions. Here, we efficiently
      manipulate polarization coupling in multilayer metasurface to promote the
      transmission of cross-polarization by Fabry-Perot resonance, so that a high
      conversion coefficient of 80-90% of CP wave is achieved within a broad bandwidth
      in the metasurface with C-shaped scatters by theoretical calculation, numerical
      simulation and experiments. Further, fully controlling Pancharatnam-Berry phase
      enables to realize polarized beam splitter, which is demonstrated to produce
      abnormal transmission with high conversion efficiency and broad bandwidth.

PMID- 27703255
TI  - Effects of histone acetylation on superoxide dismutase 1 gene expression in the
      pathogenesis of senile cataract.
AB  - Histone acetylation plays key roles in gene expression, but its effects on
      superoxide dismutase 1 (SOD1) expression in senile cataract remains unknown. To
      address this problem, the study was to investigate the influence of histone
      acetylation on SOD1 expression and its effects in the pathogenesis of senile
      cataract. Senile cataract was classified into three types-nuclear cataract (NC),
      cortical cataract (CC), and posterior subcapsular cataract (SC)-using the Lens
      Opacities Classification System III. In senile cataracts, SOD1 expression
      decreased significantly. Both H3 and H4 were deacetylated at -600 bp of the SOD1
      promoter of cataract lenses, and hypoacetylated at -1500, -1200, and -900 bp. In
      hypoacetylated histones, the hypoacetylation pattern differed among the
      cataracts. In vitro, anacardic acid (AA) significantly reduced H3 and H4
      acetylation at the SOD1 promoter, decreased protein expression, and induced
      cataract formation in rabbits. AA also inhibited HLEC viability and increased
      cell apoptosis. In contrast, trichostatin A (TSA) was able to efficaciously stop
      AA's effects on both rabbit lenses and HLECs. Decreased histone acetylation at
      the SOD1 promoter is associated with declined SOD1 expression in senile
      cataracts. Histone acetylation plays an essential role in the regulation of SOD1
      expression and in the pathogenesis of senile cataracts.

PMID- 27703256
TI  - Feature Subset Selection for Cancer Classification Using Weight Local Modularity.
AB  - Microarray is recently becoming an important tool for profiling the global gene
      expression patterns of tissues. Gene selection is a popular technology for cancer
      classification that aims to identify a small number of informative genes from
      thousands of genes that may contribute to the occurrence of cancers to obtain a
      high predictive accuracy. This technique has been extensively studied in recent
      years. This study develops a novel feature selection (FS) method for gene subset
      selection by utilizing the Weight Local Modularity (WLM) in a complex network,
      called the WLMGS. In the proposed method, the discriminative power of gene subset
      is evaluated by using the weight local modularity of a weighted sample graph in
      the gene subset where the intra-class distance is small and the inter-class
      distance is large. A higher local modularity of the gene subset corresponds to a
      greater discriminative of the gene subset. With the use of forward search
      strategy, a more informative gene subset as a group can be selected for the
      classification process. Computational experiments show that the proposed
      algorithm can select a small subset of the predictive gene as a group while
      preserving classification accuracy.

PMID- 27703257
TI  - Computer keyboard interaction as an indicator of early Parkinson's disease.
AB  - Parkinson's disease (PD) is a slowly progressing neurodegenerative disease with
      early manifestation of motor signs. Objective measurements of motor signs are of
      vital importance for diagnosing, monitoring and developing disease modifying
      therapies, particularly for the early stages of the disease when putative
      neuroprotective treatments could stop neurodegeneration. Current medical practice
      has limited tools to routinely monitor PD motor signs with enough frequency and
      without undue burden for patients and the healthcare system. In this paper, we
      present data indicating that the routine interaction with computer keyboards can
      be used to detect motor signs in the early stages of PD. We explore a solution
      that measures the key hold times (the time required to press and release a key)
      during the normal use of a computer without any change in hardware and converts
      it to a PD motor index. This is achieved by the automatic discovery of patterns
      in the time series of key hold times using an ensemble regression algorithm. This
      new approach discriminated early PD groups from controls with an AUC = 0.81 (n =
      42/43; mean age = 59.0/60.1; women = 43%/60%;PD/controls). The performance was
      comparable or better than two other quantitative motor performance tests used
      clinically: alternating finger tapping (AUC = 0.75) and single key tapping (AUC =
      0.61).

PMID- 27703258
TI  - New low-flux mixed matrix membranes that offer superior removal of protein-bound
      toxins from human plasma.
AB  - Hemodialysis is a widely available and well-established treatment for patients
      with End Stage Renal Disease (ESRD). However, although life-sustaining, patient
      mortality rates are very high. Several recent studies corroborated the link
      between dialysis patients' outcomes and elevated levels of protein-bound uremic
      toxins (PBUT) that are poorly removed by conventional hemodialysis. Therefore,
      new treatments are needed to improve their removal. Recently, our group showed
      that the combination of dialysis and adsorption on one membrane, the mixed matrix
      membrane (MMM), can effectively remove those toxins from human plasma. However,
      these first MMMs were rather large in diameter and their mass transport
      characteristics needed improvement before application in the clinical setting.
      Therefore, in this study we developed a new generation of MMMs that have a
      smaller diameter and optimized characteristics offering superior ability in
      removing the PBUT indoxyl sulfate (IS) and p-cresyl sulfate (pCS) in comparison
      to first generation MMMs (30 and 125% respectively), as well as, a commercial
      dialysis membrane (more than 100% better removal).

PMID- 27703259
TI  - Deficiency in Toll-interacting protein (Tollip) skews inflamed yet incompetent
      innate leukocytes in vivo during DSS-induced septic colitis.
AB  - Functionally compromised neutrophils contribute to adverse clinical outcomes in
      patients with severe inflammation and injury such as colitis and sepsis. However,
      the ontogeny of dysfunctional neutrophil during septic colitis remain poorly
      understood. We report that the dysfunctional neutrophil may be derived by the
      suppression of Toll-interacting-protein (Tollip). We observed that Tollip
      deficient neutrophils had compromised migratory capacity toward bacterial product
      fMLF due to reduced activity of AKT and reduction of FPR2, reduced potential to
      generate bacterial-killing neutrophil extra-cellular trap (NET), and compromised
      bacterial killing activity. On the other hand, Tollip deficient neutrophils had
      elevated levels of CCR5, responsible for their homing to sterile inflamed
      tissues. The inflamed and incompetent neutrophil phenotype was also observed in
      vivo in Tollip deficient mice subjected to DSS-induced colitis. We observed that
      TUDCA, a compound capable of restoring Tollip cellular function, can potently
      alleviate the severity of DSS-induced colitis. In humans, we observed
      significantly reduced Tollip levels in peripheral blood collected from human
      colitis patients as compared to blood samples from healthy donors. Collectively,
      our data reveal a novel mechanism in Tollip alteration that underlies the
      inflamed and incompetent polarization of neutrophils leading to severe outcomes
      of colitis.

PMID- 27703262
TI  - 4-Aminopyridine sequesters intracellular Ca2+ which triggers exocytosis in
      excitable and non-excitable cells.
AB  - 4-aminopyridine is commonly used to stimulate neurotransmitter release resulting
      from sustained plasma membrane depolarization and Ca2+-influx from the
      extracellular space. This paper elucidated unconventional mechanism of 4
      aminopyridine-stimulated glutamate release from neurons and non-neuronal cells
      which proceeds in the absence of external Ca2+. In brain nerve terminals, primary
      neurons and platelets 4-aminopyridine induced the exocytotic release of glutamate
      that was independent of external Ca2+ and was triggered by the sequestration of
      Ca2+ from intracellular stores. The initial level of 4-aminopyridine-stimulated
      glutamate release from neurons in the absence or presence of external Ca2+ was
      subequal and the difference was predominantly associated with subsequent tonic
      release of glutamate in Ca2+-supplemented medium. The increase in [Ca2+]i and the
      secretion of glutamate stimulated by 4-aminopyridine in Ca2+-free conditions have
      resulted from Ca2+ efflux from endoplasmic reticulum and were abolished by
      intracellular free Ca2+ chelator BAPTA. This suggests that Ca2+ sequestration
      plays a profound role in the 4-aminopyridine-mediated stimulation of excitable
      and non-excitable cells. 4-Aminopyridine combines the properties of depolarizing
      agent with the ability to sequester intracellular Ca2+. The study unmasks
      additional mechanism of action of 4-aminopyridine, an active substance of drugs
      for treatment of multiple sclerosis and conditions related to reduced Ca2+ efflux
      from intracellular stores.

PMID- 27703260
TI  - Dual targeting of ANGPT1 and TGFBR2 genes by miR-204 controls angiogenesis in
      breast cancer.
AB  - Deregulated expression of microRNAs has been associated with angiogenesis.
      Studying the miRNome of locally advanced breast tumors we unsuspectedly found a
      dramatically repression of miR-204, a small non-coding RNA with no previous
      involvement in tumor angiogenesis. Downregulation of miR-204 was confirmed in an
      independent cohort of patients and breast cancer cell lines. Gain-of-function
      analysis indicates that ectopic expression of miR-204 impairs cell proliferation,
      anchorage-independent growth, migration, invasion, and the formation of 3D
      capillary networks in vitro. Likewise, in vivo vascularization and angiogenesis
      were suppressed by miR-204 in a nu/nu mice model. Genome-wide profiling of MDA-MB
      231 cells expressing miR-204 revealed changes in the expression of hundred cancer
      related genes. Of these, we focused on the study of pro-angiogenic ANGPT1 and
      TGFbetaR2. Functional analysis using luciferase reporter and rescue assays
      confirmed that ANGPT1 and TGFbetaR2 are novel effectors downstream of miR-204.
      Accordingly, an inverse correlation between miR-204 and ANGPT1/TGFbetaR2
      expression was found in breast tumors. Knockdown of TGFbetaR2, but not ANGPT1,
      impairs cell proliferation and migration whereas inhibition of both genes
      inhibits angiogenesis. Taken altogether, our findings reveal a novel role for miR
      204/ANGPT1/TGFbetaR2 axis in tumor angiogenesis. We propose that therapeutic
      manipulation of miR-204 levels may represent a promising approach in breast
      cancer.

PMID- 27703261
TI  - Transcriptome and Metabolite analysis reveal candidate genes of the cardiac
      glycoside biosynthetic pathway from Calotropis procera.
AB  - Calotropis procera is a medicinal plant of immense importance due to its
      pharmaceutical active components, especially cardiac glycosides (CG). As genomic
      resources for this plant are limited, the genes involved in CG biosynthetic
      pathway remain largely unknown till date. Our study on stage and tissue specific
      metabolite accumulation showed that CG's were maximally accumulated in stems of 3
      month old seedlings. De novo transcriptome sequencing of same was done using high
      throughput Illumina HiSeq platform generating 44074 unigenes with average mean
      length of 1785 base pair. Around 66.6% of unigenes were annotated by using
      various public databases and 5324 unigenes showed significant match in the KEGG
      database involved in 133 different pathways of plant metabolism. Further KEGG
      analysis resulted in identification of 336 unigenes involved in cardenolide
      biosynthesis. Tissue specific expression analysis of 30 putative transcripts
      involved in terpenoid, steroid and cardenolide pathways showed a positive
      correlation between metabolite and transcript accumulation. Wound stress elevated
      CG levels as well the levels of the putative transcripts involved in its
      biosynthetic pathways. This result further validated the involvement of
      identified transcripts in CGs biosynthesis. The identified transcripts will lay a
      substantial foundation for further research on metabolic engineering and
      regulation of cardiac glycosides biosynthesis pathway genes.

PMID- 27703263
TI  - Unambiguous observation of blocked states reveals altered, blocker-induced,
      cardiac ryanodine receptor gating.
AB  - The flow of ions through membrane channels is precisely regulated by gates. The
      architecture and function of these elements have been studied extensively,
      shedding light on the mechanisms underlying gating. Recent investigations have
      focused on ion occupancy of the channel's selectivity filter and its ability to
      alter gating, with most studies involving prokaryotic K+ channels. Some studies
      used large quaternary ammonium blocker molecules to examine the effects of
      altered ionic flux on gating. However, the absence of blocking events that are
      visibly distinct from closing events in K+ channels makes unambiguous
      interpretation of data from single channel recordings difficult. In this study,
      the large K+ conductance of the RyR2 channel permits direct observation of
      blocking events as distinct subconductance states and for the first time
      demonstrates the differential effects of blocker molecules on channel gating.
      This experimental platform provides valuable insights into mechanisms of blocker
      induced modulation of ion channel gating.

PMID- 27703264
TI  - Epimerisation of chiral hydroxylactones by short-chain dehydrogenases/reductases
      accounts for sex pheromone evolution in Nasonia.
AB  - Males of all species of the parasitic wasp genus Nasonia use (4R,5S)-5-hydroxy-4
      decanolide (RS) as component of their sex pheromone while only N. vitripennis
      (Nv), employs additionally (4R,5R)-5-hydroxy-4-decanolide (RR). Three genes
      coding for the NAD+-dependent short-chain dehydrogenases/reductases (SDRs)
      NV10127, NV10128, and NV10129 are linked to the ability of Nv to produce RR. Here
      we show by assaying recombinant enzymes that SDRs from both Nv and N. giraulti
      (Ng), the latter a species with only RS in the pheromone, epimerise RS into RR
      and vice versa with (4R)-5-oxo-4-decanolide as an intermediate. Nv-derived SDR
      orthologues generally had higher epimerisation rates, which were also influenced
      by NAD+ availability. Semiquantitative protein analyses of the pheromone glands
      by tandem mass spectrometry revealed that NV10127 as well as NV10128 and/or
      NV10129 were more abundant in Nv compared to Ng. We conclude that the interplay
      of differential expression patterns and SDR epimerisation rates on the ancestral
      pheromone component RS accounts for the evolution of a novel pheromone phenotype
      in Nv.

PMID- 27703266
TI  - LC-MS Based Sphingolipidomic Study on A2780 Human Ovarian Cancer Cell Line and
      its Taxol-resistant Strain.
AB  - Drug resistance elicited by cancer cells continue to cause huge problems world
      wide, for example, tens of thousands of patients are suffering from taxol
      resistant human ovarian cancer. However, its biochemical mechanisms remain
      unclear. Sphingolipid metabolic dysregulation has been increasingly regarded as
      one of the drug-resistant mechanisms for various cancers, which in turn provides
      potential targets for overcoming the resistance. In the current study, a well
      established LC-MS based sphingolipidomic approach was applied to investigate the
      sphingolipid metabolism of A2780 and taxol-resistant A2780 (A2780T) human ovarian
      cancer cell lines. 102 sphingolipids (SPLs) were identified based on accurate
      mass and characteristic fragment ions, among which 12 species have not been
      reported previously. 89 were further quantitatively analyzed by using multiple
      reaction monitoring technique. Multivariate analysis revealed that the levels of
      52 sphingolipids significantly altered in A2780T cells comparing to those of
      A2780 cells. These alterations revealed an overall increase of sphingomyelin
      levels and significant decrease of ceramides, hexosylceramides and
      lactosylceramides, which concomitantly indicated a deviated SPL metabolism in
      A2780T. This is the most comprehensive sphingolipidomic analysis of A2780 and
      A2780T, which investigated significantly changed sphingolipid profile in taxol
      resistant cancer cells. The aberrant sphingolipid metabolism in A2780T could be
      one of the mechanisms of taxol-resistance.

PMID- 27703265
TI  - The Prognostic Value of PLR in Lung Cancer, a Meta-analysis Based on Results from
      a Large Consecutive Cohort.
AB  - Recently, many studies have been conducted to explore prognostic value of
      platelet to lymphocyte ratio (PLR) for patients with lung cancer, while the
      results remain controversial. We collected pretreatment, clinicopathological and
      follow-up data of 1388 lung cancer patients receiving surgery between 2006 and
      2011 in our hospital, and reviewed relevant articles from Embase, Pubmed, Web of
      science databases, then performed a meta-analysis to clarify the relationship
      between PLR and prognosis of lung cancer patients. Finally, 11 articles with our
      study were included, results indicated elevated PLR was negatively related to
      overall survival (HR = 1.33, 95% CI: 1.10-1.62), but not related to progress-free
      survival (HR = 1.21, 95% CI: 0.97-1.49). Subgroup analysis suggested high PLR was
      correlated with poor survival in non-small cell lung cancer (HR = 1.43, 95% CI:
      1.14-1.78), but not in small cell lung cancer (HR = 1.10, 95% CI: 0.76-1.58).
      Besides, for patients treated by chemotherapy or radiotherapy (HR = 1.66, 95% CI:
      1.15-2.38) and patients in late stage (HR = 1.41, 95% CI: 1.19-1.68), PLR had
      significantly prognostic value. Additionally, the result was significant for
      patients when cut-off value of PLR was between 150 and 200 (HR = 1.47, 95% CI:
      1.18-1.82). In Conclusion, this meta-analysis revealed that elevated PLR was
      associated with poor prognosis in lung cancer.

PMID- 27703267
TI  - Dietary resources shape the adaptive changes of cyanide detoxification function
      in giant panda (Ailuropoda melanoleuca).
AB  - The functional adaptive changes in cyanide detoxification in giant panda appear
      to be response to dietary transition from typical carnivore to herbivorous bear.
      We tested the absorption of cyanide contained in bamboo/bamboo shoots with a
      feeding trial in 20 adult giant pandas. We determined total cyanide content in
      bamboo shoots and giant panda's feces, levels of urinary thiocyanate and tissue
      rhodanese activity using color reactions with a spectrophotometer. Rhodanese
      expression in liver and kidney at transcription and translation levels were
      measured using real-time RT-PCR and immunohistochemistry, respectively. We
      compared differences of rhodanese activity and gene expressions among giant
      panda, rabbit (herbivore) and cat (carnivore), and between newborn and adult
      giant pandas. Bamboo shoots contained 3.2 mg/kg of cyanide and giant pandas
      absorbed more than 65% of cyanide. However, approximately 80% of absorbed cyanide
      was metabolized to less toxic thiocyanate that was discharged in urine. Rhodanese
      expression and activity in liver and kidney of giant panda were significantly
      higher than in cat, but lower than in rabbit (all P < 0.05). Levels in adult
      pandas were higher than that in newborn cub. Phylogenetic analysis of both
      nucleotide and amino acid sequences of the rhodanese gene supported a closer
      relationship of giant panda with carnivores than with herbivores.

PMID- 27703268
TI  - Optogenetic activation of septal GABAergic afferents entrains neuronal firing in
      the medial habenula.
AB  - The medial habenula (MHb) plays an important role in nicotine-related behaviors
      such as nicotine aversion and withdrawal. The MHb receives GABAergic input from
      the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that
      regulates MHb activity is unclear. GABA (gamma -aminobutyric acid) is a major
      inhibitory neurotransmitter activating both GABAA receptors and GABAB receptors.
      Depending on intracellular chloride concentration, however, GABAA receptors also
      function in an excitatory manner. In the absence of various synaptic inputs, we
      found that MHb neurons displayed spontaneous tonic firing at a rate of about ~4.4
      Hz. Optogenetic stimulation of MS/DB inputs to the MHb evoked GABAA receptor
      mediated synaptic currents, which produced stimulus-locked neuronal firing.
      Subsequent delayed yet lasting activation of GABAB receptors attenuated the
      intrinsic tonic firing. Consequently, septal GABAergic input alone orchestrates
      both excitatory GABAA and inhibitory GABAB receptors, thereby entraining the
      firing of MHb neurons.

PMID- 27703269
TI  - Rapid detection of abrin in foods with an up-converting phosphor technology-based
      lateral flow assay.
AB  - Abrin is a natural plant toxin found in the seeds of Abrus precatorius. It may be
      used for food poisoning or bioterrorism, seriously endangering public health. In
      this study, a reliable method for the rapid detection of abrin in foods was
      developed, based on an up-converting phosphor technology-based lateral flow assay
      (abrin-UPT-LFA). Nine high-affinity monoclonal antibodies (mAbs) against abrin
      were prepared, and the optimum mAbs (mAb-6F4 and mAb-10E11) were selected for use
      in the assay in double-antibody-sandwich mode. The assay was confirmed to be
      specific for abrin, with a detection sensitivity of 0.1 ng mL-1 for standard
      abrin solutions. Good linearity was observed for abrin quantitation from 0.1 to
      1000 ng mL-1 (r = 0.9983). During the analysis of various abrin-spiked food
      samples, the assay showed strong sample tolerance and a satisfactory limit of
      detection for abrin (0.5-10 ng g-1 for solid and powdered samples; 0.30-0.43 ng
      mL-1 for liquid samples). The analysis of suspected food samples, from sample
      treatment to result feed-back, could be completed by non-professionals within 20
      min. Therefore, the abrin-UPT-LFA is a rapid, sensitive, and reliable method for
      the on-site detection of abrin in foods.

PMID- 27703270
TI  - Cold tolerance and silencing of three cold-tolerance genes of overwintering
      Chinese white pine larvae.
AB  - The values of physiological indices and the enzymes activities involved in the
      overwintering stage were studied in D. armandi larvae in each month from October
      2014 to March 2015. The sorbitol, trehalose and glycerol values initially tended
      to increase as the ambient temperature decreased, before declining until the end
      of the winter. The activities of four enzymes (SOD, CAT, LDH and AchE) decreased,
      whereas POD, PK and MDH showed opposite trends in activity. Other enzyme
      activities (those of TPS, SDH and GLK) were low during the overwintering period
      and later increased and stabilized during spring. In this study, a polymerase
      chain reaction (PCR) genes of SDH, TPS and GLK was utilized to identify DarmSDH,
      DarmTPS and DarmGLK in D. armandi. They were found to be abundantly expressed
      during the overwintering stage by quantitative real-time PCR (qRT-PCR) analyses;
      by contrast, these three genes showed higher expression levels in December 2014
      than in May 2015. The qRT-PCR results demonstrated that the reduction of mRNA
      expression levels was significant in DarmSDH-, DarmTPS- and DarmGLK-dsRNA-treated
      D. armandi compared with water-injected and non-injected controls. The mortality
      responses at low temperature were also increased in the dsRNA-treated D. armandi
      compared with the controls.

PMID- 27703272
TI  - Experimental characterization of Raman overlaps between mode-groups.
AB  - Mode-division multiplexing has the potential to further increase data
      transmission capacity through optical fibers. In addition, distributed Raman
      amplification is a promising candidate for multi-mode signal amplification due to
      its desirable noise properties and the possibility of mode-equalized gain. In
      this paper, we present an experimental characterization of the intermodal Raman
      intensity overlaps of a few-mode fiber using backward-pumped Raman amplification.
      By varying the input pump power and the degree of higher order mode-excitation
      for the pump and the signal in a 10 km long two-mode fiber, we are able to
      characterize all intermodal Raman intensity overlaps. Using these results, we
      perform a Raman amplification measurement and demonstrate a mode-differential
      gain of only 0.25 dB per 10 dB overall gain. This is, to the best of our
      knowledge, the lowest mode differential gain achieved for amplification of mode
      division multiplexed signals in a single fiber.

PMID- 27703271
TI  - Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced
      Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways.
AB  - The aim of this study is to elucidate to what degree adiponectin is involved in
      TZD-mediated amelioration of neointimal formation. We investigated the effect of
      3- or 8-weeks' pioglitazone on cuff-induced neointimal formation in adiponectin
      deficient (APN-KO) and wild-type (WT) mice. Pioglitazone for 3 weeks reduced
      neointimal formation in the WT mice with upregulation of the plasma adiponectin
      levels, but failed to reduce neointimal formation in the APN-KO mice, suggesting
      that pioglitazone suppressed neointimal formation by adiponectin-dependent
      mechanisms. Pioglitazone for 3 weeks suppressed vascular smooth muscle cell
      (VSMC) proliferation and increased AdipoR2 expression in the WT mice. In vitro,
      globular adiponectin activated AMPK through both AdipoR1 and AdipoR2, resulting
      in the inhibition of VSMC proliferation. Interestingly, 8-weeks' pioglitazone was
      reduced neointimal formation in APN-KO mice to degree similar to that seen in the
      WT mice, suggesting that pioglitazone can also suppress neointimal formation via
      a mechanism independent of adiponectin. Pioglitazone for 8 weeks completely
      abrogated the increased VSMC proliferation, along with a reduction of cyclin B1
      and cyclin D1 expressions and cardiovascular risk profile in the APN-KO mice. In
      vitro, pioglitazone suppressed these expressions, leading to inhibition of VSMC
      proliferation. Pioglitazone suppresses neointimal formation via both adiponectin
      dependent and adiponectin-independent mechanisms.

PMID- 27703273
TI  - A Cretaceous origin for fire adaptations in the Cape flora.
AB  - Fire has had a profound effect on the evolution of worldwide biotas. The Cape
      Floristic Region is one of the world's most species-rich regions, yet it is
      highly prone to recurrent fires and fire-adapted species contribute strongly to
      the overall flora. It is hypothesized that the current fire regimes in the Cape
      could be as old as 6-8 million years (My), while indirect evidence indicates that
      the onset of fire could have reached 18 million years ago (Ma). Here, we trace
      the origin of fire-dependent traits in two monocot families that are significant
      elements in the fire-prone Cape flora. Our analysis shows that fire-stimulated
      flowering originated in the Cape Haemodoraceae 81 Ma, while fire-stimulated
      germination arose in the African Restionaceae at least 70 Ma, implying that
      wildfires have been a significant force in the evolution of the Cape flora at
      least 60 My earlier than previous estimates. Our results provide strong evidence
      for the presence of fire adaptations in the Cape from the Cretaceous, leading to
      the extraordinary persistence of a fire-adapted flora in this biodiversity
      hotspot, and giving support to the hypothesis that Cretaceous fire was a global
      phenomenon that shaped the evolution of terrestrial floras.

PMID- 27703275
TI  - Seven 365-Million-Year-Old Trilobites Moulting within a Nautiloid Conch.
AB  - A nautiloid conch containing many disarticulated exoskeletons of Omegops
      cornelius (Phacopidae, Trilobita) was found in the Upper Devonian Hongguleleng
      Formation of the northwestern margin of the Junggar Basin, NW China. The similar
      number of cephala, thoraces and pygidia, unbroken thoraces, explicit exuviae, and
      lack of other macrofossils in the conch, indicate that at least seven individual
      trilobites had moulted within the nautiloid living chamber, using the vacant
      chamber of a dead nautiloid as a communal place for ecdysis. This exuvial
      strategy manifests cryptic behaviour of trilobites, which may have resulted from
      the adaptive evolution induced by powerful predation pressure, unstable marine
      environments, and competition pressure of organisms occupying the same ecological
      niche in the Devonian period. The unusual presence of several trilobites moulting
      within a nautiloid conch is possibly associated with social behaviours in face of
      a serious crisis. New materials in this study open a window for understanding the
      survival strategy of marine benthic organisms, especially predator-prey
      interactions and the behavioural ecology of trilobites in the middle Palaeozoic.

PMID- 27703276
TI  - BDNF Val66Met Polymorphism Influences Visuomotor Associative Learning and the
      Sensitivity to Action Observation.
AB  - Motor representations in the human mirror neuron system are tuned to respond to
      specific observed actions. This ability is widely believed to be influenced by
      genetic factors, but no study has reported a genetic variant affecting this
      system so far. One possibility is that genetic variants might interact with
      visuomotor associative learning to configure the system to respond to novel
      observed actions. In this perspective, we conducted a candidate gene study on the
      Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, a genetic variant
      linked to motor learning in regions of the mirror neuron system, and tested the
      effect of this polymorphism on motor facilitation and visuomotor associative
      learning. In a single-pulse TMS study carried on 16 Met (Val/Met and Met/Met) and
      16 Val/Val participants selected from a large pool of healthy volunteers, Met
      participants showed significantly less muscle-specific corticospinal sensitivity
      during action observation, as well as reduced visuomotor associative learning,
      compared to Val homozygotes. These results are the first evidence of a genetic
      variant tuning sensitivity to action observation and bring to light the
      importance of considering the intricate relation between genetics and associative
      learning in order to further understand the origin and function of the human
      mirror neuron system.

PMID- 27703274
TI  - Cross-inhibition of pathogenic agents and the host proteins they exploit.
AB  - The major limitations of pathogen-directed therapies are the emergence of drug
      resistance and their narrow spectrum of coverage. A recently applied approach
      directs therapies against host proteins exploited by pathogens in order to
      circumvent these limitations. However, host-oriented drugs leave the pathogens
      unaffected and may result in continued pathogen dissemination. In this study we
      aimed to discover drugs that could simultaneously cross-inhibit pathogenic
      agents, as well as the host proteins that mediate their lethality. We observed
      that many pathogenic and host-assisting proteins belong to the same functional
      class. In doing so we targeted a protease component of anthrax toxin as well as
      host proteases exploited by this toxin. We identified two approved drugs,
      ascorbic acid 6-palmitate and salmon sperm protamine, that effectively inhibited
      anthrax cytotoxic protease and demonstrated that they also block proteolytic
      activities of host furin, cathepsin B, and caspases that mediate toxin's
      lethality in cells. We demonstrated that these drugs are broad-spectrum and
      reduce cellular sensitivity to other bacterial toxins that require the same host
      proteases. This approach should be generally applicable to the discovery of
      simultaneous pathogen and host-targeting inhibitors of many additional pathogenic
      agents.

PMID- 27703277
TI  - Repeatability of cortisol stress response in the European sea bass (Dicentrarchus
      labrax) and transcription differences between individuals with divergent
      responses.
AB  - Understanding the stress responses of organisms is of importance in the
      performance and welfare of farmed animals, including fish. Especially fish in
      aquaculture commonly face stressors, and better knowledge of their responses may
      assist in proper husbandry and selection of breeding stocks. European sea bass
      (Dicentrarchus labrax), a species with high cortisol concentrations, is of major
      importance in this respect. The main objectives of the present study were to
      assess the repeatability and consistency of cortisol stress response and to
      identify differences in liver transcription profiles of European sea bass
      individuals, showing a consistent low (LR) or high (HR) cortisol response. The
      progeny of six full sib families was used, and sampled for plasma cortisol after
      an acute stress challenge once per month, for four consecutive months. Results
      suggest that cortisol responsiveness was a repeatable trait with LR and HR fish
      showing low or high resting, free and post-stress cortisol concentrations
      respectively. Finally, the liver transcription profiles of LR and HR fish showed
      some important differences, indicating differential hepatic regulation between
      these divergent phenotypes. These transcription differences were related to
      various metabolic and immunological processes, with 169 transcripts being
      transcribed exclusively in LR fish and 161 exclusively in HR fish.

PMID- 27703278
TI  - Ghrelin Exerts Analgesic Effects through Modulation of IL-10 and TGF-beta Levels
      in a Rat Model of Inflammatory Pain.
AB  - BACKGROUND: Ghrelin is a peptide with attenuating effect on inflammatory pain.
      Both anti- and pro-inflammatory mediators have a role in the nociception and
      development of pain and hyperalgesia. IL-10 and TGF-beta are anti-inflammatory
      cytokines and inhibit the expression of pro-inflammatory cytokines related to
      peripheral and central inflammatory pain. In this study, the effects of i.p.
      injection of ghrelin on the early and the late phases of pain, as well as serum
      levels of IL-10 and TGF-beta, as anti-inflammatory cytokines, were investigated
      in formalin-induced pain in male rats. METHODS: Adult male Wistar rats (n=48)
      were randomly divided into six groups: control, formalin+saline, ghrelin (40, 80,
      and 160 MUg/kg), and morphine. Ghrelin was administered i.p. 30 min before
      inducing pain by formalin. Pain induced by intraplantar (i.pl.) injection of 50
      ul formalin 5%, and pain behavior was studied for 60 min. Serum IL-10 and TGF
      beta levels were assessed by ELISA method. RESULTS: The findings of the present
      study showed that ghrelin with high doses (80 and 160 MUg/kg) significantly
      reduced pain intensity in both the early and the late phases of pain. The serum
      levels of cytokines, IL-10, and TGF-beta1 showed a significant elevation with
      ghrelin at the dose of 160 MUg/kg. CONCLUSION: Ghrelin is effective in reducing
      the intensity of both the early and the late phases of inflammatory pain. It
      seems that ghrelin exerts its analgesic effects in part by increasing the serum
      levels of anti-inflammatory cytokines.

PMID- 27703279
TI  - An electrically resistive sheet of glial cells for amplifying signals of neuronal
      extracellular recordings.
AB  - Electrical signals of neuronal cells can be recorded non-invasively and with a
      high degree of temporal resolution using multielectrode arrays (MEAs). However,
      signals that are recorded with these devices are small, usually 0.01%-0.1% of
      intracellular recordings. Here, we show that the amplitude of neuronal signals
      recorded with MEA devices can be amplified by covering neuronal networks with an
      electrically resistive sheet. The resistive sheet used in this study is a
      monolayer of glial cells, supportive cells in the brain. The glial cells were
      grown on a collagen-gel film that is permeable to oxygen and other nutrients. The
      impedance of the glial sheet was measured by electrochemical impedance
      spectroscopy, and equivalent circuit simulations were performed to theoretically
      investigate the effect of covering the neurons with such a resistive sheet.
      Finally, the effect of the resistive glial sheet was confirmed experimentally,
      showing a 6-fold increase in neuronal signals. This technique feasibly amplifies
      signals of MEA recordings.

PMID- 27703280
TI  - In-situ guidance of individual neuronal processes by wet femtosecond-laser
      processing of self-assembled monolayers.
AB  - In-situ guidance of neuronal processes (neurites) is demonstrated by applying wet
      femtosecond-laser processing to an organosilane self-assembled monolayer (SAM)
      template. By scanning focused laser beam between cell adhesion sites, on which
      primary neurons adhered and extended their neurites, we succeeded in guiding the
      neurites along the laser-scanning line. This guidance was accomplished by
      multiphoton laser ablation of cytophobic SAM layer and subsequent adsorption of
      cell adhesion molecule, laminin, onto the ablated region. This technique allows
      us to arbitrarily design neuronal networks in vitro.

PMID- 27703281
TI  - Identification of Differentially Expressed Kinase and Screening Potential
      Anticancer Drugs in Papillary Thyroid Carcinoma.
AB  - Aim. We aim to identify protein kinases involved in the pathophysiology of
      papillary thyroid carcinoma (PTC) in order to provide potential therapeutic
      targets for kinase inhibitors and unfold possible molecular mechanisms. Materials
      and Methods. The gene expression profile of GSE27155 was analyzed to identify
      differentially expressed genes and mapped onto human protein kinases database.
      Correlation of kinases with PTC was addressed by systematic literature search, GO
      and KEGG pathway analysis. Results. The functional enrichment analysis indicated
      that "mitogen-activated protein kinases pathway" expression was extremely
      enriched, followed by "neurotrophin signaling pathway," "focal adhesion," and
      "GnRH signaling pathway." MAPK, SRC, PDGFRa, ErbB, and EGFR were significantly
      regulated to correct these pathways. Kinases investigated by the literature on
      carcinoma were considered to be potential novel molecular therapeutic target in
      PTC and application of corresponding kinase inhibitors could be possible
      therapeutic tool. Conclusion. SRC, MAPK, and EGFR were the most important
      differentially expressed kinases in PTC. Combined inhibitors may have high
      efficacy in PTC treatment by targeting these kinases.

PMID- 27703282
TI  - Analysis of the Blood Consumption for Surgical Programs.
AB  - INTRODUCTION: Transfusion is an activity that assures sufficient supply of blood
      and blood components to treat the sick and injured. In transfusion departments is
      necessary to timely provide adequate amounts of blood and blood products for
      various surgical procedures. MATERIAL AND METHODS: To determine the total amount
      of preoperative requirements (BT/AB and BT/AB/MT) for blood and blood products in
      surgical departments of General Hospital "Prim. Dr. Abdulah Nakas" in the period
      from June 1, 2014 - December 31, 2014 and analyze the requirements for blood in
      relation to surgical procedures, surgical discipline, period, age and gender of
      patients. To determine the maximum consumption levels surgeries. RESULTS: The
      total amount of preoperative requirements for blood and blood products in
      surgical departments amounted to 927. Almost the same number of requests with a
      slightly higher percentage was in December and October and the lowest in June.
      The average age of patients was 52.2+/-20.1 years with the youngest patient aged
      9 and the oldest at the age of 97 years. Women were more prevalent with 686 or
      74% of the time compared to men. The largest number of requests for surgery
      elective cesarean section 208 (22.5%) with delivery wards, then for surgery or
      hip replacement 98 (10.6%). Maximum consumption for surgical operations
      Hysterectomy totalis abdominals 15 doses of blood. CONCLUSION: The largest number
      of requests were for elective cesarean section 208 (22.5%) with delivery wards,
      then for surgery or hip replacement with 98 (10.6%). Maximum consumed doses had
      gynecology surgery at Hysterectomy totalis abdominals 15 doses of blood, then
      orthopedics surgery at Primary hip prosthesis 11 doses.

PMID- 27703283
TI  - Inflammatory Cytokines as Risk Factors for Mortality After Acute Cardiac Events.
AB  - INTRODUCTION: Inflammatory markers have been identified as potential indicators
      of future adverse outcome after acute cardiac events. AIM: This study aimed to
      analyze baseline inflammatory cytokines levels in patients with acute heart
      failure (AHF) and/or acute coronary syndrome (ACS) according to survival. The
      main objective was to identify risk factors for mortality after an episode of AHF
      and/or ACS. METHODS: In this prospective longitudinal study 75 patients with the
      diagnosis of AHF and/or ACS were enrolled. Baseline laboratory and clinical data
      were retrieved. Serum and urine interleukin-6 (IL-6) and interleukin-18 (IL-18)
      levels, plasma B-type natriuretic peptide (BNP) and serum cystatin C values were
      determined. The primary outcome was in-hospital mortality while secondary outcome
      was six-month mortality. RESULTS: Median serum and urine IL-6 levels, serum and
      urine IL-18 levels, as well as median concentrations of plasma BNP and serum
      cystatin C, were significantly increased in deceased in comparison to surviving
      AHF and/or ACS patients. Univariate Cox regression analysis identified serum IL
      6, serum IL-18, urine IL-6, urine IL-18 as well as serum cystatin C and Acute
      Physiology and Chronic Health Evaluation (APACHE) II score as risk factors for
      mortality after an episode of AHF and/or ACS. Multivariate Cox regression
      analysis revealed that only serum IL-6 is the independent risk factor for
      mortality after acute cardiac events (HR 61.7, 95% CI 2.1-1851.0; p=0.018).
      CONCLUSION: Present study demonstrated the strong prognostic value of serum IL-6
      in predicting mortality of patients with AHF and/or ACS.

PMID- 27703285
TI  - Studying the Relation of Postprandial Triglyceride with Coronary Artery Disease
      (CAD).
AB  - BACKGROUND: Coronary artery disease (CAD) is the most common cause of mortality
      worldwide and determination of contributing factors is essential. AIM: This study
      was conducted to study the relation of postprandial triglyceride as a risk of
      coronary artery disease in patients with proven CAD by angiography, referred to
      502 Hospital of Army in 2015. MATERIAL AND METHODS: This observational study
      conducted as a case-control and contained 80 male participants referred to 502
      Hospital of Army. Half of these participants had proven CAD by angiography test
      and the other ones were healthy as a control group. Fasting serum triglyceride
      was evaluated in all participants and postprandial TG was checked 4 hours after a
      standard meal. Obtained data were analyzed by SPSS ver. 13. RESULTS: The results
      indicated that fasting TG and postprandial TG level were significantly higher in
      CAD patients (P-value=0.001). It was also shown evaluation of postprandial TG is
      more sensitive test than fasting TG in case of CAD patients. CONCLUSION: Our
      obtained results shown, evaluation of high level of postprandial TG is more
      reliable than fasting TG for patients whom suffer from CAD.

PMID- 27703284
TI  - Pre-operative Neutrophils/Lymphocyte Ratio in Rectal Cancer Patients with
      Preoperative Chemoradiotherapy.
AB  - BACKGROUND: Several studies have reported that an elevation in
      neutrophils/lymphocyte ratio (NLR) is correlated with poor survival in patients
      with colorectal cancer, but in rectal cancer (RC), it has been reported only in a
      few studies. It is necessary to separate colon cancer and rectal cancer to
      clarify the prognostic significance of NLR, especially in patients who received
      chemoradiotherapy. METHODS: It is a comparative, observational retrospective
      study of a cohort of 175 patients. We grouped the patients into two based on
      their NLR (0-3 vs. > 3) to correlate with disease-specific survival (DSS) and
      pathologic complete response (pCR). RESULTS: The average NLR was 2.65 + 1.32
      (range 0.58-6.89), and 144 (82.3%) patients had an NLR of 0-3. The median follow
      up was 33.53 months. There were no differences in pCR between the two groups. The
      5-year DSS was 78.8%. NLR did not correlate with survival. Mesorectal quality,
      pT3-4 tumors, lymph node metastasis, lymphovascular invasion, perineural
      invasion, positive margins and recurrence were statistically significant
      predictors of increased mortality in univariate analysis. In multivariate
      analysis, only overall recurrence correlated with poor survival. The analysis of
      the association of NLR with outcomes with different cut points (2.0, 2.5, 4 and
      5) did not show differences in DSS and pCR. CONCLUSION: In our cohort, the NLR
      did not serve as a prognostic marker in patients with locally advanced rectal
      cancer and who received chemoradiotherapy and did not correlate with pCR as well.

PMID- 27703286
TI  - A Comparison Between the Hemodynamic Effects of Cisatracurium and Atracurium in
      Patient with Low Function of Left Ventricle who are Candidate for Open Heart
      Surgery.
AB  - BACKGROUND: The need for muscle relaxants in general anesthesia in different
      surgeries including cardiac surgeries, and the type of relaxant to be used
      considering its different hemodynamic effects on patients with heart disease can
      be of considerable importance. In this study, the hemodynamic effects of two
      muscle relaxants, Cisatracurium and Atracurium in patients whit low function of
      left ventricle who are candidate for open heart surgery have been considered.
      METHOD: This study has been designed as a randomized prospective double-blind
      clinical trial. The target population included all adult patients with heart
      disease whose ejection fraction reported by echocardiography or cardiac
      catheterization was 35% or less before the surgery, and were candidate for open
      heart surgery in Shahid Rajaei Heart Center. Taking into account the inclusion
      and exclusion criteria, the patients were randomly placed in two groups of 30
      people each. In the induction stage, all the patients received midazolam,
      etomidate, and one of the considered muscle relaxant, either 0.2 mg/kg of
      cisatracurium or 0.5mg/kg of Atracurium within one minute. In the maintenance
      stage of anesthesia, the patients were administered by infusion of midazolam,
      sufentanil and the same muscle relaxant used in the induction stage. The
      hemodynamic indexes were recorded and evaluated in different stages of anesthesia
      and surgery as well as prior to transfer to ICU. RESULTS: In regard with
      descriptive indexes (age and sex distributions, premedication with cardiac drugs,
      ejection fraction before surgery, basic disease) there was no statistically
      significant difference between the groups. CONCLUSIONS: The significant
      difference of hemodynamic indexes between the two groups of this study, and the
      need for hemodynamic stability in all stages of surgery for patients with low
      function of left ventricle who are candidate for open heart surgery, proves that
      administering Cisatracurium as the muscle relaxant is advantageous and better.

PMID- 27703287
TI  - A Comparison of Prognostic Value of the Levels of ProBNP and Troponin T in
      Patients with Acute Coronary Syndrome (ACS).
AB  - INTRODUCTION: The propeptide of brain natriuretic peptide (ProBNP) is used for
      the diagnosis of left ventricle dysfunction and heart failure. In patients with
      an Acute Coronary Syndrome (ACS) it can contribute to both short and long term
      prognosis of cardiovascular events that could be very important for management
      and therapy of these patients. AIM: The aim of this study was to evaluate the
      prognostic value of ProBNP for the clinical course after an acute coronary
      syndrome, compared with that of cardiac troponine T (cTnT) and the risk
      stratification of patients with acute coronary syndrome, both during
      hospitalization and six months later. METHODS: We studied 390 patients (256 men,
      134 women, mean age 66.04+12.38) with an acute coronary syndrome who were
      hospitalized in the Coronary Unit of our cardiology clinic. We studied
      epidemiological and clinical data and biochemical markers were examined as
      prognostic factors for clinical course intrahospital and during six months follow
      up. RESULTS: In the majority of patients, a myocardial infarction without ST
      elevation was diagnosed (NSTEMI) (193 patients 49.49%) while 167 patients
      (42.82%) had a myocardial infarction with ST elevation (STEMI) and the remaining
      30 patients (7.69%) had unstable angina. Patients had multiple risk factors for
      coronary heart disease. The levels of ProBNP were significantly elevated in
      patients with STEMI (p=0.003) and NSTEMI (p=0.002) who died or experienced an
      adverse event (angina, myocardial infarction, cardiogenic shock, congestive heart
      failure, arrhythmias) during hospitalization. After six months of follow-up,
      patients who had an adverse event had higher levels of ProBNP. There was no
      difference in troponine T levels in patients with STEMI and NSTEMI who had
      adverse events compared with the others, either during hospitalization or after
      six months. CONCLUSION: The level of ProBNP is an important predictor of
      cardiovascular events in patients with acute coronary syndrome. This study showed
      that it provides better predictive power than the troponine T.

PMID- 27703288
TI  - Blood Pressure Control in Hypertensive Patients, Cardiovascular Risk Profile and
      the Prevalence of Masked Uncontrolled Hypertension (MUCH).
AB  - INTRODUCTION: The term masked hypertension (MH) should be used for untreated
      individuals who have normal office blood pressure but elevated ambulatory blood
      pressure. For treated patients, this condition should be termed masked
      uncontrolled hypertension (MUCH). RESEARCH OBJECTIVES: Masked uncontrolled
      hypertension (MUCH) has gone unrecognized because few studies have used 24-h ABPM
      to determine the prevalence of suboptimal BP control in seemingly well-treated
      patients, and there are few such studies in large cohorts of treated patients
      attending usual clinical practice. This is important because masked hypertension
      is associated with a high risk of cardiovascular events. This study was conducted
      to obtain more information about the association between hypertension and other
      CV risk factors, about office and ambulatory blood pressure (BP) control as well
      as on cardiovascular (CV) risk profile in treated hypertensive patients, also to
      define the prevalence and characteristics of masked uncontrolled hypertension
      (MUCH) among treated hypertensive patients in routine clinical practice. PATIENTS
      AND METHODS: In this study 2514 male and female patients were included during a
      period of 5 years follow up. All patients have ambulatory blood pressure
      monitoring (ABPM) for at least 24h. We identified patients with treated and
      controlled BP according to current international guidelines (clinic BP,
      140/90mmHg). Cardiovascular risk assessment was based on personal history, clinic
      BP values, as well as target organ damage evaluation. Masked uncontrolled
      hypertension (MUCH) was diagnosed in these patients if despite controlled clinic
      BP, the mean 24-h ABPM average remained elevated (24-h systolic BP >=130mmHg
      and/or 24-h diastolic BP >=80mmHg). RESULTS: Patients had a mean age of 60.2+10
      years, and the majority of them (94.6%) were followed by specialist physicians.
      Average clinic BP was 150.4+16/89.9+12 mmHg. About 70% of patients displayed a
      very high-risk profile. Ambulatory blood pressure monitoring (ABPM) was performed
      in all recruited patients for at least 24h. Despite the combined medical
      treatment (78% of the patients), clinic control (<140/90 mmHg) was achieved in
      only 26.2% of patients, the corresponding control rate for ambulatory BP (<130/80
      mmHg) being 32.7%. From 2514 patients with treated BP, we identified 803 with
      treated and controlled office BP control (<140/90 mmHg), of whom 258 patients
      (32.1%) had MUCH according to 24-h ABPM criteria (mean age 57.2 years, 54.7%
      men). The prevalence of MUCH was slightly higher in males, patients with
      borderline clinic and office BP (130-139/80-89 mmHg), and patients at high
      cardiovascular risk (smokers, diabetes, obesity). Masked uncontrolled
      hypertension (MUCH) was most often due to poor control of nocturnal BP, with the
      proportion of patients in whom MUCH was solely attributable to an elevated
      nocturnal BP almost double that solely attributable to daytime BP elevation (22.3
      vs. 10.1%, P 0.001). CONCLUSION: The prevalence of masked suboptimal BP control
      in patients with treated and well-controlled clinic BP is high. The
      characteristics of patients with MUCH (male, longer duration of hypertension,
      obesity, smoking history, and diabetes) indicate that this is a higher-risk group
      with most to gain from improved BP.

PMID- 27703289
TI  - Comparison of Manual Refraction Versus Autorefraction in 60 Diabetic Retinopathy
      Patients.
AB  - AIM: The purpose of the study was to evaluate the comparison of manual refraction
      versus autorefraction in diabetic retinopathy patients. MATERIAL AND METHODS: The
      study was conducted at the Be'sat Army Hospital from 2013-2015. In the present
      study differences between two common refractometry methods (manual refractometry
      and Auto refractometry) in diagnosis and follow up of retinopathy in patients
      affected with diabetes is investigated. RESULTS: Our results showed that there is
      a significant difference in visual acuity score of patients between manual and
      auto refractometry. Despite this fact, spherical equivalent scores of two methods
      of refractometry did not show a significant statistical difference in the
      patients. CONCLUSION: Although use of manual refraction is comparable with
      autorefraction in evaluating spherical equivalent scores in diabetic patients
      affected with retinopathy, but in the case of visual acuity results from these
      two methods are not comparable.

PMID- 27703290
TI  - Short-term Outcomes of Induced Membrane Technique in Treatment of Long Bone
      Defects in Iran.
AB  - INTRODUCTION: Severe defects in long bones can be caused by several factors such
      as trauma that lead to open wound and secondary infections after surgery. Induced
      membrane technique is one of the therapeutic strategies that can be used for
      these patients. Due to importance of this method and lack of information about
      this technique in Iran. AIM: this study was performed to investigate technical
      strengths and weakness of induced membrane technique. MATERIAL AND METHODS: This
      case series study conducted on 21 patients with bone defects in the femur and
      tibia and metatarsal bones referred to orthopedic clinic of Rasoul Akram
      Hospital, Tehran, Iran, for induced membrane surgery in 2012-2015. Demographic
      and clinical data were obtained using history, clinical examinations and
      observations for each patient. Union achievement was the main outcome of this
      study, which was confirmed by radiographic findings and physical examination.
      Obtained data was analyzed by SPSS ver. 16. RESULTS: All patients were male
      except one and their mean age was 30.52 years old. Bone defects were in tibia,
      femur and metatarsus in 9, 9 and 3 patients, respectively. Three patients
      received soft tissue reconstruction with flap before induced membrane surgery.
      Age, defects size, cigarette addiction and drug use and delay to start the
      treatment had no significant effect on union status. In total, 90% of patients
      had successful surgery. CONCLUSION: using induced membrane technique in patients
      with defects in their long bone such as tibia, femur and metatarsus would lead to
      high success for reconstruction.

PMID- 27703291
TI  - Actual Contribution of Free to Total PSA Ratio in Prostate Diseases
      Differentiation.
AB  - OBJECTIVES: To determine significance and sensitivity of the Free to Total
      prostate specific antigen (PSA) ratio (%fPSA) in diagnosis of prostate cancer and
      to correlate its sensitivity and specificity with diagnosis. METHODS: Research
      included 220 patients, who had indication for biopsy (Clinic for Urology,
      University Clinical Center Sarajevo). RESULTS: Average age of patients was 64.6
      +/- 8.1 years. Kruskal Wallis test indicates that there is a significant
      difference in age in relation to the diagnosis (KW chi2=12.508; p=0.006). The
      correlation between the %fPSA level and diagnosis is positive and statistically
      significant (r=0.211; p=0.002) in the sense that cancer patients have the lowest
      %fPSA. Analysis of the sensitivity at 95% specificity of %fPSA compared to
      particular diagnosis shows the highest sensitivity for prostate cancer - 20.61%
      (8.35-31.02) with statistically significant AUC p<0.05. Analysis of %fPSA test in
      detecting prostate cancer, at cut-off values <= 0.16, shows a sensitivity of
      72.3% and specificity of 50.4 (at cut-off values <0.07, sensitivity is 8.4%, and
      specificity is 97.8%). CONCLUSION: PSA is organ specific but not cancer specific
      marker, whose total value, as well as the %fPSA serve as a basis, with a
      digitorectal exam, in the detection of prostate cancer. By increasing the cut-off
      values sensitivity of %fPSA increases and specificity decreases. %fPSA has a
      relative importance in the detection of prostate cancer, and should not be used
      as a guideline, without prior clinical examination.

PMID- 27703292
TI  - Evaluation of Patellar Position before and After Medial Opening Wedge High Tibial
      Osteotomy: Radiographic and Computed Tomography Findings.
AB  - INTRODUCTION: Genovarum is a common orthopedic problem. Its optimal prompt
      treatment is an issue of importance. AIM: This study was conducted to determine
      the radiographic changes in patella bone before and after open wedge high tibial
      osteotomy. MATERIAL AND METHODS: In this quasi-experimental study, 43 patients
      were enrolled and underwent open wedge high tibial osteotomy and the radiographic
      and CT-scan indices including Q-Angle, Congruence Angle, Insall-Salvati index,
      and TTTG were measured and compared before and after surgery. RESULTS: The result
      revealed that all indices including Q-Angle, Congruence Angle, Insull-Salvati
      index, and TTTG were not significantly differed across the study (P > 0.05).
      There was no difference between DLFA values before and after the operation (P>
      0.05), while MPTA values were significantly different before and after operation
      (p <0.001). CONCLUSIONS: Totally it may be concluded that imaging indices are not
      differed after open wedge high tibial osteotomy and monitoring for them is not
      necessary and they would have no prognostic role.

PMID- 27703293
TI  - Diagnostic Approach to Patients with Atypical Squamous Cells of Undetermined
      Significance Cytologic Findings on Cervix.
AB  - BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) is a
      term that refers to inflammatory, reactive and reparative processes which are
      atypical and of higher level and insufficient to be classified as cervical
      intraepithelial lesions (CIN). AIMS: Examine of frequency of HPV infection in
      ASCUS lesions and regression, stagnation and progression during six-month period.
      SUBJECTS AND METHODS: Prospective study was conducted over a period of 3 years.
      In private gynecological ambulance "Dr Mahira Jahic". Analysis of PAP smears and
      HPV typization have been done in 50 patients and PAP test has been repeated after
      six months. X2 test was used for statistical analysis. RESULTS: Analysis of 1784
      PAP smears showed normal results in 86,6% (N-1530), and abnormal in 13% (N-254).
      ASCUS in 7,4% (N-133) and ASC-H in 0,5% (N-9), LSIL in 4,4% (N-80), HSIL in 1,3%
      (N-24), CIN II in 1,2% (N-20), CIN III in 0,2% (N-4). Progression occurred in 18%
      (9), persistence in 74% (37) and regression in 8%. Patients with ASC-H lesion
      0,5% (N-9), PH results showed 22% (N-2) Carcinoma in situ, 33% (N-3) CIN II, 22%
      (N-2) CIN I and 22% (N-2) chronic cervicitis. Patients with CIN I in 88% (N-7)
      were positive on HPV of high risk. Patients with persistent ASCUS result were
      positive in 51% (N-19). The number of CIN I lesions found in women with ASCUS is
      bigger and statistically significant (p<0,05) in relation to number of CIN I
      findings found in regular examinations. CONCLUSION: Monitoring women with ASCUS
      lesion, especially HPV positive to high risk group is the best way of selection
      of women who should be treated and monitored in order to prevent cervical cancer.

PMID- 27703294
TI  - Treatment of Hypertension with Combination of Lisinopril/Hydrochlorothiazide.
AB  - INTRODUCTION: Paper is written on the basis of data collected in collaboration
      with family doctors in several cities in Bosnia and Herzegovina. MATERIAL AND
      METHODS: In this retrospective, randomized study was carried out processing of
      data collected by special design questionnaire from the field through studies and
      analyzes carried out in 5 health care institutions in the territory of Bosnia and
      Herzegovina. The study included 270 patients who underwent three consecutive
      medical examinations. RESULTS: Total reduction in blood pressure in average was
      32.8 mmHg for systolic and 17.1 mmHg for diastolic, which is consistent with
      previously published results. Lisinopril/Hydrochlorothiazide is therefore a
      valuable therapy in the field of internal medicine. Study of this medication
      confirmed its efficacy in the treatment of hypertension. CONCLUSION: Control of
      high blood pressure in our patients according to data was very low, so it is
      necessary to intensify measures of prevention and treatment.

PMID- 27703295
TI  - Pulmonary Hypertension - New Trends of Diagnostic and Therapy.
AB  - Pulmonary hypertension is a pathophysiological state hemodynamically defined as
      the increase of the mean pulmonary arterial pressure above 25, or 30 mmHg at
      rest, measured by catheterization of the right heart. Laboratory findings usually
      reveals polycythemia, the ECG right ventricle hypertrophy, and x-ray
      characteristic of diseased branches (echocardiography and biomarkers such as B
      type natriuretic peptide (BNP) and N-terminal pro-BNP hormones are potentially
      helpful tools in identifying PH). Echocardiography can be found the increase of
      the right atrium and ventricle, right ventricular hypertrophy, abnormal
      contraction of the interventricular septum, left ventricular diastolic
      dysfunction and decreased left ventricular size, with reduced volumes of systole
      and end diastole. Doppler confirming tricuspid regurgitation. Pharmacological
      therapy would represent a use: Calcium Channel Blockers, Prostacyclin Analogues,
      Endothelin Receptor Antagonists and Phosphodiesterase-5 Inhibitors. Alpha
      adrenergic antagonists, endothelial receptor subtype A (Bosentan, Tracller) with
      treatment of the underlying disease or anticongestive therapy, are recommended.
      In case of inadequate response to treatment with a specific drug, guidelines
      recommend the combined use of drugs from the basic three groups, using their
      synergism.

PMID- 27703296
TI  - Rhabdomyolysis in Critically Ill Surgical Patients.
AB  - INTRODUCTION: Rhabdomyolysis is a syndrome of injury of skeletal muscles
      associated with myoglobinuria, muscle weakness, electrolyte imbalance and often,
      acute kidney injury as severe complication. THE AIM: of this study is to detect
      the incidence of rhabdomyolysis in critically ill patients in the surgical
      intensive care unit (ICU), and to raise awareness of this medical condition and
      its treatment among the clinicians. MATERIAL AND METHODS: A retrospective review
      of all surgical and trauma patients admitted to surgical ICU of the University
      Surgical Clinic "Mother Teresa" in Skopje, Macedonia, from January 1st till
      December 31st 2015 was performed. Patients medical records were screened for
      available serum creatine kinase (CK) with levels > 200 U/l, presence of myoglobin
      in the serum in levels > 80 ng/ml, or if they had a clinical diagnosis of
      rhabdomyolysis by an attending doctor. Descriptive statistical methods were used
      to analyze the collected data. RESULTS: Out of totally 1084 patients hospitalized
      in the ICU, 93 were diagnosed with rhabdomyolysis during the course of one year.
      82(88%) patients were trauma patients, while 11(12%) were surgical non trauma
      patients. 7(7.5%) patients diagnosed with rhabdomyolysis developed acute kidney
      injury (AKI) that required dialysis. Average values of serum myoglobin levels
      were 230 ng/ml, with highest values of > 5000 ng/ml. Patients who developed AKI
      had serum myoglobin levels above 2000 ng/ml. Average values of serum CK levels
      were 400 U/l, with highest value of 21600 U/l. Patients who developed AKI had
      serum CK levels above 3000 U/l. CONCLUSION: Regular monitoring and early
      detection of elevated serum CK and myoglobin levels in critically ill surgical
      and trauma patients is recommended in order to recognize and treat rhabdomyolysis
      in timely manner and thus prevent development of AKI.

PMID- 27703297
TI  - Primary Central Nervous System Anaplastic Large T-cell Lymphoma.
AB  - INTRODUCTION: Primary central nervous system lymphoma (PCNSL) of T-cell origin is
      an exceptionally rare, highly malignant intracranial neoplasm. Although such a
      tumor typically presents with a focal mass lesion. CASE REPORT: Past medical
      history of a 26-year-old male patient with a PCNS lymphoma of T-cell origin was
      not suggestive of intracranial pathology or any disorder of other organs and
      organic systems. To achieve a gross total tumor resection, surgery was performed
      via osteoplastic craniotomy using the left frontal transcortical transventricular
      approach. Histological and immunohistochemical analyses of the tissue removed
      described tumor as anaplastic large cell lymphoma of T-cells (T-ALCL).
      Postoperative and neurological recovery was complete, while control imaging of
      the brain showed no signs of residual tumor at a six-month follow-up. The
      patient, who did not appear immunocompromized, was referred to a hematologist and
      an oncologist where corticosteroids, the particular chemotherapeutic protocol and
      irradiation therapy were applied. CONCLUSION: Since PCNS lymphoma is a
      potentially curable brain tumor, we believe that proper selection of the
      management options, including early radical tumor resection for solitary PCNS
      lymphoma, may be proposed as a major treatment of such a tumor in selected
      patients, resulting in a satisfactory outcome.

PMID- 27703298
TI  - Management of the Patient with Aggressive and Resistant Papillary Thyroid
      Carcinoma.
AB  - PURPOSE: Papillary carcinoma is the most frequent type of thyroid cancer and was
      considered the most benign of all thyroid carcinomas, with a low risk of distant
      metastases. However, there are some variants of papillary thyroid carcinoma that
      have affinity to spread in many organs, such as: lymph nodes, lungs and bones.
      AIM: The aim of this study was presentation of a case with papillary carcinoma of
      the thyroid gland, very persistent and resistant in treatment with I 131.
      MATERIAL AND RESULTS: A man 56 years old were diagnosed with papillary carcinoma
      of thyroid gland. He underwent a surgical removal of the tumor and right lobe of
      thyroid gland. With histopathology examination, were confirmed follicular variant
      of papillary carcinoma pT4. Two weeks later he underwent total thyroidectomy and
      was treated with 100 mCi of J 131. Six months later, the value of thyroglobulin
      was found elevated above upper measured limits (more than 500 ng/ml). Patient
      underwent surgical removal of 10 metastatic lymph nodes in the left side of the
      neck and has been treated with 145 mCi of radioiodine I 131. The examination
      after 5 months shows elevation of thyroglobulin, more than 20000 ng/ml and
      focally uptake of J 131 in the left lung. Patient was treated once again with 150
      mCi radioiodine J 131. Whole body scintigraphy was registered focal uptake of
      radioiodine in the middle of the left collarbone. After a month, patient refers
      the enlargement of the lymph node in the right side of the neck. Currently
      patient is being treated with kinase inhibitor drug sorafenib and ibandronate. We
      have identified first positive response in treatment. Enlarged lymph node in the
      neck was reduced and the patient began feeling better. CONCLUSION: This study
      suggests that some subtypes of papillary thyroid carcinoma appear to have more
      aggressive biological course. Subtypes of papillary thyroid carcinoma such as
      diffuse sclerosing carcinoma, tall cell or columnar cell and insular variants,
      appears to have more aggressive biological course and need early detection and
      other kind of treatment.

PMID- 27703299
TI  - Metastasis of Prostate Adenocarcinoma to the Testis.
AB  - INTRODUCTION: Prostate carcinoma is the most frequently diagnosed carcinoma in
      the male population. The most typical places of the metastases are pelvic
      lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis.
      The prognostic importance of testicular metastasis of prostate cancer is not yet
      well-known, due to a very few published cases. According to the known facts, it
      is certain that a metastasis of the prostate carcinoma into a testis is a sign of
      an advanced disease. CASE REPORT: This work presents a 48-year-old patient, to
      whom an adenocarcinoma of the prostate has been proven by the pathohistological
      finding of transrectal biopsy, performed due to the elevated level of prostate
      specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual
      rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy
      and right orchectomy were performed. Metastatic dissemination of prostate
      adenocarcinoma into a testis was determined by a pathohistological analysis of
      the left testis. CONCLUSION: The metastasis of the prostate carcinoma into a
      testis, as a rare localization of the metastatic dissemination, after
      additionally performed orchectomy along with further oncological therapy, can
      provide a continuation of a good life quality as well as a control of the disease
      in a longer time period.

PMID- 27703300
TI  - A Modified Wrapping-internal Shunt Method for Hemostasis in Bentall Procedure.
AB  - INTRODUCTION: Blindly punching between aorta and right atrium is dangerous. In
      that case, there is concerned about leakage between the two referred isolate
      parts. Besides, as the routine imaging techniques (echocardiography or computer
      tomography) are incompetent to detect this particular anatomic structure
      preoperatively, the intraoperative inspection appears necessary. Our method is
      useful for identifying this innate fusion plane. CASE REPORT: The thrombosis
      surrounding prosthesis was detected in the first ultrasound examination after the
      operation, which was considered to be an indication of successful hemostasis. As
      the innate fusion between aorta and right atrium appears no rare, the selective
      creation of left-to-right internal shunt is a valuable maneuver for controlling
      bleeding in appropriate cases.

PMID- 27703301
TI  - P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to
      Reduce Vascular Inflammation.
AB  - Inflammation is a common process associated with numerous vascular pathologies.
      We hypothesized that targeting the inflamed endothelium by coupling a peptide
      with high affinity for P-selectin to the surface of dexamethasone-loaded lipid
      nanoemulsions will highly increase their specific binding to activated
      endothelial cells (EC) and reduce the cell activation. We developed and
      characterized dexamethasone-loaded lipid nanoemulsions directed towards P
      selectin (PLN-Dex) and monitored their anti-inflammatory effects in vitro using
      cultured EC (EA.hy926 cells) and in vivo using a mouse model of acute
      inflammation [lipopolysaccharides (LPS) intravenously administered in C57BL/6
      mice]. We found that PLN-Dex bound specifically to the surface of activated EC
      are efficiently internalized by EC and reduced the expression of proinflammatory
      genes, thus preventing the monocyte adhesion and transmigration to/through
      activated EC. Given intravenously in mice with acute inflammation, PLN-Dex
      accumulated at a significant high level in the lungs (compared to nontargeted
      nanoemulsions) and significantly reduced mRNA expression level of key
      proinflammatory cytokines such as IL-1beta, IL-6, and MCP-1. In conclusion, the
      newly developed nanoformulation, PLN-Dex, is functional in vitro and in vivo,
      reducing selectively the endothelium activation and the consequent monocyte
      infiltration and diminishing significantly the lungs' inflammation, in a mouse
      model of acute inflammation.

PMID- 27703302
TI  - SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease
      (Uveitis).
AB  - Uveitis is a potentially sight-threatening disease characterized by repeated
      cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates
      the differentiation of pathogenic Th1 and Th17 cells that mediate uveitis. A
      SOCS1 mimetic peptide (SOCS1-KIR) that inhibits JAK2/STAT1 pathways has recently
      been shown to suppress experimental autoimmune uveitis (EAU). However, it is not
      clear whether SOCS1-KIR ameliorated uveitis by targeting JAK/STAT pathways of
      pathogenic lymphocytes or via inhibition of macrophages and antigen-presenting
      cells that also enter the retina during EAU. To further investigate mechanisms
      that mediate SOCS1-KIR effects and evaluate the efficacy of SOCS1-KIR as an
      investigational drug for chronic uveitis, we induced EAU in rats by adoptive
      transfer of uveitogenic T-cells and monitored disease progression and severity by
      slit-lamp microscopy, histology, and optical coherence tomography. Topical
      administration of SOCS1-KIR ameliorated acute and chronic posterior uveitis by
      inhibiting Th17 cells and the recruitment of inflammatory cells into retina while
      promoting expansion of IL-10-producing Tregs. We further show that SOCS1-KIR
      conferred protection of resident retinal cells that play critical role in vision
      from cytotoxic effects of inflammatory cytokines by downregulating proapoptotic
      genes. Thus, SOCS1-KIR suppresses uveitis and confers neuroprotective effects and
      might be exploited as a noninvasive treatment for chronic uveitis.

PMID- 27703304
TI  - The Burden of Pediatric Encephalitis in the United States.
AB  - Investigators from the University of Maryland, University of Colorado, and
      Arkansas Children's Hospital studied the epidemiology, management and resource
      utilization of children admitted to hospitals in the United States with
      encephalitis.

PMID- 27703305
TI  - Pediatric Intracranial Hypertension.
AB  - Investigators from the Ohio State University, Oregon Health and Science
      University and Rosalind Franklin School of Medicine examined the presenting
      manifestations, demographics and treatment strategies in children enrolled in the
      Intracranial Hypertension Registry (IHR).

PMID- 27703303
TI  - Regulation of IL-33 by Oncostatin M in Mouse Lung Epithelial Cells.
AB  - IL-33 modulates both innate and adaptive immune responses at tissue sites
      including lung and may play critical roles in inflammatory lung disease. Although
      IL-33 expression can be altered upon NF-Kappa B activation, here we examine
      regulation by Oncostatin M, a gp130 cytokine family member, in mouse lung tissue.
      Responses were assessed in BALB/c mouse lung at day 7 of transient overexpression
      using endotracheally administered adenovirus encoding OSM (AdOSM) or empty vector
      (AdDel70). Whole lung extracts showed induction of IL-33 mRNA (>20-fold) and
      protein (10-fold increase in immunoblots) by AdOSM relative to AdDel70.
      Immunohistochemistry for IL-33 indicated a marked induction of nuclear staining
      in alveolar epithelial cells in vivo. Oncostatin M stimulated IL-33 mRNA and IL
      33 full length protein in C10 mouse type 2 alveolar epithelial cells in culture
      in time-dependent and dose-dependent fashion, whereas IL-6, LIF, IL-31, IL-4, or
      IL-13 did not, and TGFbeta repressed IL-33. IL-33 induction was associated with
      activation of STAT3, and pharmacological inhibition of STAT3 ameliorated IL-33
      levels. These results indicate Oncostatin M as a potent inducer of IL-33 in mouse
      lung epithelial cells and suggest that an OSM/IL-33 axis may participate in
      innate immunity and inflammatory conditions in lung.

PMID- 27703306
TI  - p27KIP1 loss promotes proliferation and phagocytosis but prevents epithelial
      mesenchymal transition in RPE cells after photoreceptor damage.
AB  - PURPOSE: p27KIP1 (p27), originally identified as a cell cycle inhibitor, is now
      known to have multifaceted roles beyond cell cycle regulation. p27 is required
      for the normal histogenesis of the RPE, but the role of p27 in the mature RPE
      remains elusive. To define the role of p27 in the maintenance and function of the
      RPE, we investigated the effects of p27 deletion on the responses of the RPE
      after photoreceptor damage. METHODS: Photoreceptor damage was induced in wild
      type (WT) and p27 knockout (KO) mice with N-methyl-N-nitrosourea (MNU) treatment.
      Damage-induced responses of the RPE were investigated with bromodeoxyuridine
      (BrdU) incorporation assays, immunofluorescence, and terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) assays at different stages after MNU
      treatment. Subcellular localization of p27 in the WT RPE was also analyzed in
      vivo and in vitro. RESULTS: MNU treatment induced photoreceptor-specific
      degeneration in the WT and KO retinas. BrdU incorporation assays revealed
      virtually no proliferation of RPE cells in the WT retinas while, in the KO
      retinas, approximately 16% of the RPE cells incorporated BrdU at day 2 after MNU
      treatment. The RPE in the KO retinas developed aberrant protrusions into the
      outer nuclear layer in response to photoreceptor damage and engulfed outer
      segment debris, as well as TUNEL-positive photoreceptor cells. Increased
      phosphorylation of myosin light chains and their association with rhodopsin
      positive phagosomes were observed in the mutant RPE, suggesting possible
      deregulation of cytoskeletal dynamics. In addition, WT RPE cells exhibited
      evidence of the epithelial-mesenchymal transition (EMT), including morphological
      changes, induction of alpha-smooth muscle actin expression, and attenuated
      expression of tight junction protein ZO-1 while these changes were absent in the
      KO retinas. In the normal WT retinas, p27 was localized to the nuclei of RPE
      cells while nuclear and cytoplasmic p27 was detected in RPE cells undergoing EMT,
      suggesting a role for cytoplasmic p27 in the phenotype changes of RPE cells.
      CONCLUSIONS: p27 loss promoted proliferation and phagocytic activity of RPE cells
      while preventing EMT after photoreceptor damage. These findings provide evidence
      for the role of p27 in the control of RPE responses to retinal damage.

PMID- 27703307
TI  - Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve
      crush model.
AB  - PURPOSE: This study was conducted to determine whether alpha lipoic acid (ALA)
      promotes the survival of retinal ganglion cells (RGCs) in a rat model of optic
      nerve crush (ONC) injury and to investigate the neuroprotective mechanisms of ALA
      in the retina in this ONC injury model. METHODS: Adult male Sprague-Dawley rats
      (180-220 g) were subjected to ONC injury surgery. ALA (63 mg/kg) was injected
      intravenously 1 day before or after the ONC injury. Animals were euthanized after
      10 days, and the number of ganglion cells positive for RNA-binding protein with
      multiple splicing (Rbpms), which is an RGC marker, were counted on the whole
      mount retinas. In addition, immunofluorescence and immunoblotting were performed
      to examine the localization and levels of erythropoietin receptor (EPOR) and
      neurotrophin-4/5 (NT4/5) in the retinas in all experimental groups. To determine
      whether the EPO/EPOR signaling pathway was involved in the ALA antioxidant
      pathway, the rats were subjected to ruxolitinib (INCB018424, 0.25 mg/kg, bid,
      intraperitoneal, i.p.) treatment after the animals were injected intravenously
      with ALA 1 day before ONC injury. RESULTS: The average number of Rbpms-positive
      cells/mm2 in the control group (sham-operated group), the ONC group, the ALA-ONC
      group, and the ONC-ALA group retinas was 2219+/-28, 418+/-8, 848+/-22, and 613+/
      18/mm2, respectively. The ALA-ONC and ONC-ALA groups showed a statistically
      significantly increased RGC survival rate compared to the ONC group. There were
      statistical differences in the RGC survival rates between the ALA-ONC (39%) and
      ONC-ALA groups (28%; p<0.05). Immunofluorescent labeling showed that EPOR and
      NT4/5 expression was significant in the retinal ganglion cell layer (GCL). At the
      same time, western blot analysis revealed that ALA induced upregulation of EPOR
      protein and NT4/5 protein expression in the retina after ONC injury. However,
      INCB018424 reversed the protective effects of ALA on the ONC retinas.
      CONCLUSIONS: ALA has neuroprotective effects on RGCs after ONC injury. Moreover,
      prophylactic administration of ALA may have a stronger neuroprotective effect
      against ONC-induced damage. Based on these data, we also conclude that the
      endogenous EPO/EPOR signaling pathway may contribute to the protective effects of
      ALA in the retina after ONC injury.

PMID- 27703309
TI  - Gastrectomy for gastric carcinoma with situs inversus totalis: case report and
      literature review.
AB  - BACKGROUND: Situs inversus totalis (SIT), a rare congenital anomaly, is
      characterized by a complete mirror image transposition of the thoracic and
      abdominal viscera. We report the case of a 66-year-old woman with SIT who was
      diagnosed with gastric antral carcinoma. Curative distal gastrectomy with
      Billroth-I anastomosis was performed. Description of the case: A 66-year-old
      woman visited our outpatient department complaining of abdominal pain in the left
      upper quadrant for about one year. Physical examination revealed that the apex
      beat was in the right fifth intercostal space, just at the midclavicular line
      while a soft systolic murmur was audible at the upper right sternal border. The
      abdominal examination was unremarkable. The preoperative diagnosis was confirmed
      by gastroscopy and biopsy. Preoperative echocardiogram revealed the presence of
      dextrocardia and atrial septal defect. Preoperative contrasted computed
      tomography showed a complete right-left reversal of the thoracic and abdominal
      organs and thickened wall of gastric antrum without distant metastasis.
      Laparotomy through a midline incision confirmed the complete mirror-image
      transposition of the abdominal visceral organs and a 4-cm tumor with serosal
      involvement at the gastric antrum. Curative distal gastrectomy with D2
      lymphadenectomy and Billroth-I anastomosis was performed. The patient had a rapid
      recovery and was discharged without any complications. The final staging of this
      case was pT4aN1M0, stage IIIa and she received chemotherapy with the SOX regimen
      for three cycles. Fifteen months after the operation, the patient is alive
      without any signs of recurrence. CONCLUSIONS: The incidence of gastric cancer
      with SIT is very rare. Appropriate diagnostic modalities are very helpful for the
      diagnosis and preoperative planning. Gastrectomy with D2 lymphadenectomy in
      patients with SIT can be performed successfully with sufficient preoperative
      evaluation, comprehensive knowledge of anatomy, and meticulous surgical
      manipulation. Caution should be given to the possibility of coexisting
      cardiopulmonary malformations and synchronous cancers. Hippokratia 2015; 19 (4):
      360-362.

PMID- 27703310
TI  - "Bath Salts" intoxication with multiorgan failure and left-sided ischemic
      colitis: a case report.
AB  - BACKGROUND: In the recent years, a new group of designer drugs, under the brand
      name of bath salts has emerged as a new trend. They are mainly b-ketone
      amphetamine analogs and are derivatives of cathinone, a monoamine alkaloid. They
      are abused for psychostimulant effects. Their primary ingredient 3,4
      methylenedioxypyrovalerone (MDPV), has alerted authorities worldwide due to its
      severe physiological and behavioral toxicities. Description of Case:We present
      the case of a 47-year-old man with coma, seizures, multi-organ failure and
      ischemic colitis after intoxication with bath salts containing MDPV. After
      supportive care, he had a successful outcome. To our knowledge, this report is
      the first to describe ischemic colitis after MDPV intoxication. Clinicians need
      to be especially alert since MDPV is not detected by routine screens, and its
      overdose can be life-threatening. CONCLUSION: Ischemic colitis should be
      recognized as a potential complication of bath salts ingestion in order to
      prevent unnecessary interventions, such as diagnostic laparotomy, which could
      worsen patient's condition. Hippokratia 2015; 19 (4): 363-365.

PMID- 27703308
TI  - Citrullination of glial intermediate filaments is an early response in retinal
      injury.
AB  - PURPOSE: A hallmark of retinal gliosis is the increased detection and
      modification of the type III intermediate filament (IF) proteins vimentin and
      glial fibrillary acidic protein (GFAP). Here, we investigated vimentin and GFAP
      in Muller glia in a mouse model of alkali injury, focusing on the
      posttranslational modification of citrullination. METHODS: Mice were injured by
      corneal exposure to 1.0 N NaOH, and eyes were enucleated at different time points
      following injury. The levels of soluble and cytoskeletal forms of IF proteins and
      citrullination were measured using western blot analysis. Citrullinated GFAP was
      identified by immunoprecipitation followed by two-dimensional (2D) isoelectric
      focusing-polyacrylamide gel electrophoresis (IEF-PAGE) western blotting using a
      specific antibody that recognizes citrullinated GFAP. Vimentin, GFAP, and
      citrullinated proteins were localized in the retina by immunohistochemistry
      (IHC). Drug treatments were investigated in retinal explant cultures of posterior
      eyecups obtained from mouse eyes that were injured in vivo. RESULTS: Detection of
      GFAP in injured retinas increased over a period of 1 to 7 days, showing increased
      levels in both soluble and cytoskeletal forms of this IF protein. The global
      level of citrullinated proteins was also induced over this period, with low-salt
      buffer extraction showing the most abundant early changes in citrullination.
      Using IHC, we found that GFAP filaments assembled at Muller glial end feet,
      growing in size with time through the inner layers of the retina at 1-3 h
      postinjury. Interestingly, over this early time period, levels of soluble
      citrullinated proteins also increased within the retina, as detected by western
      blotting, coincident with the localization of the citrullinated epitopes on
      growing GFAP filaments and existing vimentin filaments by 3 h after injury.
      Taking advantage of the in vivo injury model to promote a robust gliotic
      response, posterior eyecups from 7-day postinjured eyes were treated in explant
      cultures with the peptidyl arginine deiminase inhibitor Cl-amidine, which was
      found to reduce global citrullination. Surprisingly, the detection of injury
      induced high-molecular-weight GFAP species containing citrullinated epitopes was
      also reduced by Cl-amidine treatment. Using a low dose of the potent type III IF
      drug withaferin A (WFA), we showed that Cl-amidine treatment in combination with
      WFA reduced global protein citrullination further, suggesting that GFAP may be a
      key component of pathological citrullinated targets. CONCLUSIONS: Our findings
      illuminate citrullination as a potential novel target for trauma-induced retinal
      gliosis. We also propose that strategies for combining drugs targeting type III
      IFs and citrullination may potentiate tissue repair, which is an idea that needs
      to be validated in vivo.

PMID- 27703311
TI  - Multi-digit contracture release using medial sural artery perforator flap with
      syndactylization-desyndactylization method.
AB  - BACKGROUND: The medial sural artery perforator flap, with a long pedicle, has
      tremendous potential for applications in a variety of soft tissue defects. It can
      be used for reconstruction of multi-digit contractures of the palmar region.
      MATERIALS AND METHODS: We present herein the key features of the management of
      postburn multi-digit volar contractures, using medial sural artery perforator
      flaps with the syndactylization and desyndactylization method. We describe the
      use of the free medial sural artery perforator flap in two patients, to
      reconstruct complex composite hand defects including the second, third, fourth
      and fifth digits following thermal burns. RESULTS: Both flaps healed
      uneventfully. In both patients, the hand contractures released completely and
      adequate joint motion was achieved after a 3-month period of physiotherapy.
      CONCLUSIONS: The thin medial sural artery perforator flap permits high accuracy
      of soft tissue reconstruction of the hand and reduces the morbidity at the donor
      site. The MSAPF is a useful flap in areas such as the hands, in the case of soft
      tissue deficiency and tendon exposition. Hippokratia 2015; 19 (4): 366-368.

PMID- 27703312
TI  - Alphan uncommon coexistence of primary sexual, cough and exercise headaches: the
      first three cases from Greece.
AB  - BACKGROUND: The "other primary headaches" encompasses a group of uncommon but
      distinct headache disorders. The coexistence of their subforms such as primary
      sexual and exercise headache is not a new phenomenon, but in association with
      cough headache is rather uncommon. Report of cases: We report three cases with a
      rare coexistence of primary cough, exercise and associated with sexual activity
      headache. Indomethacin was effective in all patients. The leading
      pathophysiological explanation involves a rapid rise in intra-abdominal pressure
      exertional factors or an inappropriate reaction in the cerebral vasculature.
      CONCLUSIONS: Further studies are needed to confirm a common pathogenic mechanism
      in these patients. Tauhe coexistence of these headaches needs to be taken into
      account in the final classification that is expected to be available in 2016.
      Hippokratia 2015; 19 (4): 369-371.

PMID- 27703313
TI  - An unusual case of Streptococcus agalactiae meningitis in a patient with sys
      temic lupus erythematosus.
AB  - BACKGROUND: Streptococcus agalactiae (group B Streptococcus) is a major cause of
      sepsis and meningitis in neonates and an important cause of invasive disease in
      adults. CASE DESCRIPTION: We describe an unusual case of fatal bacterial
      meningitis caused by Streptococcus agalactiae in a young man suffering from
      systemic lupus erythematosus for over 20 years. The young man was transferred
      intubated in AHEPA University Hospital in a coma; twenty-four hours upon arrival
      and despite intense invasive treatment, he died from multiple organ failure.
      CONCLUSION: The risk of serious infections in patients with systemic lupus
      erythematosus even under treatment with moderate doses of corticosteroids is
      high. Hippokratia 2015; 19 (4):372-373.

PMID- 27703314
TI  - A rare case of Guillain-Barre syndrome presenting with abdominal pain.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) is a heterogeneous condition that
      encompasses acute immune-mediated polyneuropathies. GBS is the most frequent
      cause of acute neuromuscular paralysis worldwide and constitutes one of the most
      serious emergencies in neurology. Description of case: As it presents extremely
      rarely with the first symptom being abdominal pain, herein we report the case of
      a 48-year-old man who presented with acute abdominal pain and diagnosed with GBS.
      The patient required mechanical ventilation for two weeks and was discharged one
      month later, after having had a tracheostomy and developed tetraplegia.
      CONCLUSION: GBS should be included in the differential diagnosis of acute
      abdominal pain when other medical or surgical causes have been excluded.
      Hippokratia 2015; 19 (4): 374-375.

PMID- 27703315
TI  - A case of extensive varicosities of the vulva in a term pregnancy.

PMID- 27703316
TI  - Investigation of potential pro-coagulation activity markers in healthy
      individuals.

PMID- 27703317
TI  - The role of tacrolimus in the step-up induction therapy of refractory childhood
      onset lupus nephritis.

PMID- 27703318
TI  - Juvenile myelomonocytic leukemia in a 14-month-old boy presenting with acute
      respiratory failure.

PMID- 27703319
TI  - Careful pre-anesthetic evaluation leading to a successful anesthetic management
      of an undiagnosed Duchenne muscular dystrophy child.

PMID- 27703320
TI  - Child onset steroid-dependent nephrotic syndrome with a combination of mini-mal
      glomerular changes and IgA deposits: long-term follow-up.

PMID- 27703321
TI  - An unusual case of hemolysis in a patient with cirrhosis.

PMID- 27703322
TI  - The effect of Frappe coffee on blood lipid levels.

PMID- 27703323
TI  - Toric intraocular lens orientation and residual refractive astigmatism: an
      analysis.
AB  - PURPOSE: To analyze intraocular lens (IOL) orientation data from an online toric
      back-calculator (astigmatismfix.com) for determining if differences were apparent
      by lens type. METHODS: A retrospective review of astigmatismfix.com toric back
      calculations that included IOL identification and intended orientation axis.
      RESULTS: Of 12,812 total validated calculation records, 8,229 included intended
      orientation and lens identification data. Of the latter, 5,674 calculations (69%)
      involved lenses oriented 5 degrees  or more from their intended position. Using
      estimated toric lens usage data, the percentage of lenses with orientation >=5
      degrees  from intended was 0.89% overall, but the percentage varied significantly
      between specific toric lens brands (P<0.05). The percentage of back-calculations
      related to lenses that were not oriented as intended was also statistically
      significantly different by lens brand (P<0.05). When IOLs were misoriented, they
      were significantly more likely to be misoriented in a counterclockwise direction
      (P<0.05). This was found to be due to a bias toward counterclockwise orientation
      observed with one specific brand, a bias that was not observed with the other
      three brands analyzed here. CONCLUSION: The percentage of eyes with lens
      orientation >=5 degrees  from intended in the Toric Results Analyzer data set was
      <1% of toric IOLs in general, with the relative percentage of Tecnis(r) Toric
      IOLs significantly higher than AcrySof(r) Toric IOLs. Both of these had higher
      rates than the Staar(r) Toric and Trulign(r) Toric lenses, with the availability
      of higher Tecnis and AcrySof cylinder powers a likely contributing factor. The
      AcrySof Toric IOL appears to be less likely than the Tecnis Toric IOL to cause
      residual astigmatism as a result of misorientation. The Tecnis Toric IOL appears
      more likely to be misoriented in a counterclockwise direction; no such bias was
      observed with the AcrySof Toric, the Trulign(r) Toric, or the Staar Toric IOLs.

PMID- 27703324
TI  - Preservative-free bimatoprost 0.03%/timolol 0.5% fixed combination in patients
      with glaucoma in clinical practice.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy and tolerability of,
      and compliance to, preservative-free (PF), fixed-combination (FC) bimatoprost
      0.03%/timolol 0.5% in patients with primary open-angle glaucoma or ocular
      hypertension in a clinical practice setting. PATIENTS AND METHODS: This open
      label study observed patients switched to PF FC bimatoprost 0.03%/timolol 0.5%
      due to insufficient intraocular pressure (IOP) control on previous therapies. IOP
      was measured at baseline and at ~12 weeks. Tolerability and continuation of
      therapy were also assessed. RESULTS: A total of 1,553 patients were included in
      the study, and the per-protocol population comprised 1,391 patients. There were
      some minor deviations from protocol: some patients with no prior therapy and some
      who switched for reasons other than insufficient IOP control were included in the
      analysis. The mean IOP was reduced by 27.4%, from 22.2 mmHg to 16.1 mmHg. In
      subgroup analyses, the mean IOP was significantly reduced from baseline,
      irrespective of whether previous treatment was monotherapy or combination
      therapy, and preserved or PF therapy. Physicians mostly (88.1%) reported the IOP
      lowering efficacy of PF FC bimatoprost 0.03%/timolol 0.5% to be as expected or
      better than expected. Switching to PF FC bimatoprost 0.03%/timolol 0.5% resulted
      in reductions from baseline in the number of patients reporting ocular symptoms.
      Adverse events were reported by 6.2% of patients, the most common being eye
      irritation (1.6%) and eye pruritus (1.0%). Physicians reported treatment
      compliance as better or unchanged compared with prior treatment in almost all
      patients (93.9%). Most patients were expected to continue PF FC bimatoprost
      0.03%/timolol 0.5% after the end of the study. CONCLUSION: Switching to PF FC
      bimatoprost 0.03%/timolol 0.5% was associated with significant IOP reductions
      from baseline over 12 weeks. Adverse events were uncommon, and compliance was
      high compared with previous therapy. PF FC bimatoprost 0.03%/timolol 0.5% may be
      a suitable treatment for patients with inadequately controlled IOP or who are
      sensitive to preservatives.

PMID- 27703325
TI  - A comparison of pop and chop to divide and conquer in resident cataract surgery.
AB  - In this randomized prospective study, the cumulative dissipated energy and case
      time of pop and chop and of traditional four-quadrant divide and conquer in the
      first 60 cases (in total 120 eyes) of cataract surgery performed by two residents
      at the Veterans Administration Hospital in Hampton, Virginia, were compared.
      Overall and individually, the residents had significantly shorter case times and
      used significantly less cumulative dissipated energy for performing pop and chop
      than that for divide and conquer technique. There was no difference in
      complication rates or visual outcomes between these two techniques. The results
      of this study suggest that pop and chop is a more time- and energy-efficient
      method of nucleofractis than divide and conquer for novice resident surgeons.

PMID- 27703326
TI  - Intravitreal ziv-aflibercept for macular edema following retinal vein occlusion.
AB  - AIM: To report the efficacy of intravitreal ziv-aflibercept injections in eyes
      with macular edema due to retinal vein occlusions (RVOs). METHODS: Consecutive
      patients with persistent or recurrent macular edema (central macula thickness
      >250 MUm) due to RVO were enrolled in this prospective study. Study eyes received
      intravitreal injections of ziv-aflibercept (1.25 mg/0.05 mL) at baseline.
      Patients were reassessed monthly for 4 months and given additional injections pro
      re nata for worsening best-corrected visual acuity (BCVA), intraretinal edema or
      subretinal fluid seen on spectral domain optical coherence tomography, or central
      macular thickness (CMT) measurements >250 MUm. The primary endpoint was
      improvement in mean CMT at 4 months. Secondary endpoints included improvement in
      mean BCVA, and ocular and systemic safety signals. RESULTS: Nine eyes (five
      central and four branch RVOs) of nine patients were enrolled. The mean +/-
      standard deviation CMT decreased from 604+/-199 MUm at baseline to 319+/-115 MUm
      (P=0.001) at 1 month and to 351+/-205 MUm (P=0.026) at 4 months. The mean BCVA
      did not improve significantly from baseline (1.00 LogMAR) to the 1-month (0.74
      LogMAR; P=0.2) and 4-month (0.71 LogMAR; P=0.13) visits. No safety signals were
      noted. CONCLUSION: In this small prospective study, intravitreal ziv-aflibercept
      significantly improved mean CMT in eyes with persistent or recurrent macular
      edema due to RVOs. Prospective, randomized trials comparing ziv-aflibercept with
      standard pharmacotherapy are needed to better define efficacy and safety.

PMID- 27703328
TI  - Effect of low dose of intrathecal pethidine on the incidence and intensity of
      shivering during cesarean section under spinal anesthesia: a randomized, placebo
      controlled, double-blind clinical trial.
AB  - INTRODUCTION: Shivering is among the unpleasant and potentially harmful side
      effects of spinal anesthesia. The aim of this randomized double-blind clinical
      trial was to compare the antishivering effect of two different doses of
      intrathecal pethidine on the incidence and intensity of shivering and other side
      effects in patients who underwent cesarean section. METHODS: In this study, 150
      parturient females scheduled for nonemergent cesarean section were randomly
      allocated to three groups. Spinal anesthesia was performed with 0.5% hyperbaric
      bupivacaine (12.5 mg), plus 0.5 mL of 0.9% saline in the standard group (S
      group), and the same dose of bupivacaine with 5 mg (P5 group) or 10 mg of
      pethidine (P10 group). Demographic and surgical data, incidence and intensity of
      shivering (primary outcome), hemodynamic indices, forehead and core temperatures,
      maximum sensory level, Apgar scores, and adverse events were evaluated by a
      blinded observer. RESULTS: There were no significant differences between the
      three study groups regarding the demographic and surgical data, hemodynamic
      indices, core temperatures, and maximum sensory level (P>0.05). The incidence and
      intensity of shivering were significantly less in the P5 and P10 groups (P<0.001)
      when compared with the S group. There were no significant differences between
      groups for secondary outcomes, except pruritus, which was more common in the P5
      and P10 groups when compared with the S group (P=0.01). CONCLUSION: Low dose of
      intrathecal pethidine is safe, and can decrease the incidence and intensity of
      shivering during cesarean section, without having major side effects.

PMID- 27703327
TI  - Eag1 channels as potential early-stage biomarkers of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide. HCC is
      usually asymptomatic at potential curative stages, and it has very poor prognosis
      if detected later. Thus, the identification of early biomarkers and novel
      therapies is essential to improve HCC patient survival. Ion channels have been
      proposed as potential tumor markers and therapeutic targets for several cancers
      including HCC. Especially, the ether a-go-go-1 (Eag1) voltage-gated potassium
      channel has been suggested as an early marker for HCC. Eag1 is overexpressed
      during HCC development from the cirrhotic and the preneoplastic lesions preceding
      HCC in a rat model. The channel is also overexpressed in human HCC. Astemizole
      has gained great interest as a potential anticancer drug because it targets
      several proteins involved in cancer including Eag1. Actually, in vivo studies
      have shown that astemizole may have clinical utility for HCC prevention and
      treatment. Here, we will review first some general aspects of HCC including the
      current biomarkers and therapies, and then we will focus on Eag1 channels as
      promising tools in the early diagnosis of HCC.

PMID- 27703329
TI  - Bulgecin A as a beta-lactam enhancer for carbapenem-resistant Pseudomonas
      aeruginosa and carbapenem-resistant Acinetobacter baumannii clinical isolates
      containing various resistance mechanisms.
AB  - Genetic screening of Pseudomonas aeruginosa (PSDA) and Acinetobacter baumannii
      (ACB) reveals genes that confer increased susceptibility to beta-lactams when
      disrupted, suggesting novel drug targets. One such target is lytic
      transglycosylase. Bulgecin A (BlgA) is a natural product of Pseudomonas
      mesoacidophila and a lytic transglycosolase inhibitor that works synergistically
      with beta-lactams targeting PBP3 for Enterobacteriaceae. BlgA also weakly
      inhibits di-Zn2+ metallo-beta-lactamases like L1 of Stenotrophomonas maltophilia.
      We hypothesized that because of its unique mechanism of action, BlgA could
      restore susceptibility to carbapenems in carbapenem-resistant PSDA (CR-PSDA) and
      carbapenem-resistant ACB, as well as ACB resistant to sulbactam. A BlgA
      containing extract was prepared using a previously published protocol. CR-PSDA
      clinical isolates demonstrating a variety of carbapenem resistance mechanisms
      (VIM-2 carbapenemases, efflux mechanisms, and AmpC producer expression) were
      characterized with agar dilution minimum inhibitory concentration (MIC) testing
      and polymerase chain reaction. Growth curves using these strains were prepared
      using meropenem, BlgA extract, and meropenem plus BlgA extract. A concentrated
      Blg A extract combined with low concentrations of meropenem, was able to inhibit
      the growth of clinical strains of CR-PSDA for strains that had meropenem MICs >=8
      mg/L by agar dilution, and a clinical strain of an OXA-24 producing ACB that had
      a meropenem MIC >32 mg/L and intermediate ampicillin/sulbactam susceptibility.
      Similar experiments were conducted on a TEM-1 producing ACB strain resistant to
      sulbactam. BlgA with ampicillin/sulbactam inhibited the growth of this organism.
      As in Enterobacteriaceae, BlgA appears to restore the efficacy of meropenem in
      suppressing the growth of CR-PSDA and carbapenem-resistant ACB strains with a
      variety of common carbapenem resistance mechanisms. BlgA extract also inhibits
      VIM-2 beta-lactamase in vitro. BlgA may prove to be an exciting adjunctive
      compound to extend the life of carbapenems against these vexing pathogens.

PMID- 27703330
TI  - Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations
      of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy
      subjects: a randomized, open-label, single-dose, two-period, two-sequence
      crossover study.
AB  - BACKGROUND: A fixed-dose combination (FDC) of amlodipine and losartan has been
      used to reduce blood pressure in patients whose hypertension is not sufficiently
      controlled with either drug alone. The aim of this study was to evaluate the
      pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg
      amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an
      FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects.
      SUBJECTS AND METHODS: A randomized, open-label, single-dose, two-period, two
      sequence crossover study was conducted on 46 healthy male subjects. Blood
      concentrations were measured by liquid chromatography-tandem mass spectrometry.
      Blood samples were collected up to 144 hours post dose for each period. PK
      parameters were calculated in each treatment group using a noncompartmental
      method. The 90% confidence intervals (CIs) of the geometric mean ratios of the
      two treatments for the maximum plasma concentration (Cmax) and the area under the
      concentration curve from time zero to the last quantifiable time point (AUC0-t)
      were estimated. Tolerability assessments were performed for all subjects who
      received the drug at least once. RESULTS: The PK profiles of the two treatments
      were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine
      besylate to amlodipine camsylate for the Cmax and AUC0-t were 0.98 (0.94-1.01)
      and 0.97 (0.93-1.01), respectively. The corresponding values for losartan were
      0.91 (0.81-1.02) and 1.05 (0.98-1.12), respectively. The incidence of adverse
      events was not significantly different between the two treatments, and both were
      well tolerated. CONCLUSION: An FDC of 6.94 mg amlodipine besylate (5 mg as
      amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg
      amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK
      parameters of amlodipine and losartan based on Cmax and AUC0-t values. The
      amlodipine besylate/losartan potassium combination was well tolerated by healthy
      male subjects.

PMID- 27703331
TI  - The spice for joint inflammation: anti-inflammatory role of curcumin in treating
      osteoarthritis.
AB  - Osteoarthritis is a degenerative disease of the joint affecting aging populations
      worldwide. It has an underlying inflammatory cause, which contributes to the loss
      of chondrocytes, leading to diminished cartilage layer at the affected joints.
      Compounds with anti-inflammatory properties are potential treatment agents for
      osteoarthritis. Curcumin derived from Curcuma species is an anti-inflammatory
      compound as such. This review aims to summarize the antiosteoarthritic effects of
      curcumin derived from clinical and preclinical studies. Many clinical trials have
      been conducted to determine the effectiveness of curcumin in osteoarthritic
      patients. Extracts of Curcuma species, curcuminoids and enhanced curcumin, were
      used in these studies. Patients with osteoarthritis showed improvement in pain,
      physical function, and quality of life after taking curcumin. They also reported
      reduced concomitant usage of analgesics and side effects during treatment. In
      vitro studies demonstrated that curcumin could prevent the apoptosis of
      chondrocytes, suppress the release of proteoglycans and metal metalloproteases
      and expression of cyclooxygenase, prostaglandin E-2, and inflammatory cytokines
      in chondrocytes. These were achieved by blocking the activation of nuclear factor
      kappa-light-chain-enhancer of activated B cells (NF-kappaB) system in the
      chondrocytes, by preventing the activation of nuclear factor of kappa light
      polypeptide gene enhancer in B-cells inhibitor, alpha, phosphorylation, and
      translocation of the p65 subunit of NF-kappaB complexes into the nucleus. In
      conclusion, curcumin is a potential candidate for the treatment of
      osteoarthritis. More well-planned randomized control trials and enhanced curcumin
      formulation are required to justify the use of curcumin in treating
      osteoarthritis.

PMID- 27703332
TI  - Controlled release of TGF-beta 1 from RADA self-assembling peptide hydrogel
      scaffolds.
AB  - Bioactive mediators, cytokines, and chemokines have an important role in
      regulating and optimizing the synergistic action of materials, cells, and
      cellular microenvironments for tissue engineering. RADA self-assembling peptide
      hydrogels have been proved to have an excellent ability to promote cell
      proliferation, wound healing, tissue repair, and drug delivery. Here, we report
      that D-RADA16 and L-RADA16-RGD self-assembling peptides can form stable second
      structure and hydrogel scaffolds, affording the slow release of growth factor
      (transforming growth factor cytokine-beta 1 [TGF-beta 1]). In vitro tests
      demonstrated that the plateau release amount can be obtained till 72 hours.
      Moreover, L-RADA16, D-RADA16, and L-RADA16-RGD self-assembling peptide hydrogels
      containing TGF-beta 1 were used for 3D cell culture of bone mesenchymal stem
      cells of rats for 2 weeks. The results revealed that these three RADA16 peptide
      hydrogels had a significantly favorable influence on proliferation of bone
      mesenchymal stem cells and hold some promise in slow and sustained release of
      growth factor.

PMID- 27703333
TI  - Satisfaction and associated factors of outpatient psychiatric service consumers
      in Ethiopia.
AB  - PURPOSE: The purpose of this study was to assess the level of patient
      satisfaction and associated factors with psychiatric outpatient services in
      Ethiopia. PATIENTS AND METHODS: A cross-sectional study was performed from May
      2015 to June 2015. A total of 454 participants selected by systematic random
      sampling were included in this study. Pretested and interviewer-administered
      questionnaire was used to collect the data. Patient satisfaction was measured
      using Charleston Psychiatric Outpatient Satisfaction Scale, and other validated
      tools were used to assess the associated variables. Multivariate logistic
      regressions with 95% confidence interval (CI) were used to assess the strength,
      and P-value <0.05 was used to indicate significance of association. RESULTS: A
      total of 441 respondents were enrolled, with a response rate of 97.1% and
      magnitude of satisfaction of 61.2%. Being male (adjusted odds ratio [AOR] =0.612,
      95% CI: 0.39, 0.94), being widowed (AOR =0.13, 95% CI: 0.05, 0.36), urban
      residence (AOR =0.49, 95% CI: 0.31, 0.78), diagnosed with schizophrenia (AOR
      =0.48, 95% CI: 0.28, 0.81), unfavorable attitude (AOR =0.49, 95% CI: 0.28, 0.86),
      and poor social functioning (AOR =0.52, 95% CI: 0.34, 0.80) were significantly
      associated with satisfaction. CONCLUSION: More than one-third of psychiatric
      service consumers were dissatisfied with the service they received. Integrating
      patients to their own treatment plan and regular service evaluation are important
      to improve satisfaction.

PMID- 27703334
TI  - Patients' attitudes to the use of modern technologies in the treatment of
      diabetes.
AB  - BACKGROUND: The incidence of diabetes is rising across the world. This global
      problem significantly affects the economic and social development in the 21st
      century. If the disease is diagnosed in time, the number of complications as well
      as the costs of therapy will be lower. Modern technologies permeate all spheres
      of medicine, and diabetes treatment is no exception. Therefore, the aim of this
      article is to analyze patients' attitudes to the use of modern technologies in
      the treatment of diabetes (type 1 diabetes mellitus [T1DM] and type 2 diabetes
      mellitus [T2DM]). METHODS: A total of 313 respondents from the Czech Republic in
      the period from June 24, 2015, to July 24, 2015, participated in a questionnaire
      survey. The target group was diabetics regardless of the type of illness.
      Collected data were analyzed using descriptive statistical methods, Z-test, and
      test of independence (Pearson's chi-squared test). RESULTS: Although in other
      areas mobile applications are used to monitor patients' health condition in ~30%
      of cases, in the case of diabetes they are used by only 4% of respondents.
      Approximately 8% of participants use an application, but they do not like it. The
      rest of the respondents have never used any mobile application. These low figures
      are due to a lack of knowledge about the availability and possibilities of mobile
      applications. A positive correlation was proven between technical skills and
      methods of entering data. Gender and age show only a weak dependency of the
      method of writing data on their own health condition. Furthermore, the monitored
      parameters show that patients with T1DM control and know more about their health
      condition than patients with T2DM, which is reflected, for example, by more
      frequent blood glucose measurements or larger track of their physical activity.
      Conversely, the relationship between the associated complications and self-care
      activities has not been demonstrated. CONCLUSION: Despite the current fast
      development of modern technologies, these technologies are not frequently used in
      treating patients. The principal problem lies in patients' low technological
      knowledge and their higher age, which makes learning new skills, including the
      use of modern technologies, more difficult.

PMID- 27703335
TI  - Evaluation of factors associated with psychiatric patient dropout at a university
      outpatient clinic in Japan.
AB  - BACKGROUND: Patient dropout from treatment can lead to a deterioration in
      clinical condition, thereby increasing the need for more intensive therapy that
      incurs substantial social and economic losses. The aim of this study was to
      identify factors related to psychiatric patient dropout at a university
      outpatient clinic in Japan. METHODS: We retrospectively examined the medical
      charts of new psychiatric patients who were diagnosed with either a mood disorder
      (International Classification of Diseases, 10th revision, code: F3) or an anxiety
      disorder (F4) in the outpatient clinic at Kyoto Prefectural University of
      Medicine Hospital in Kyoto, Japan, between April 2010 and March 2013. The
      baseline characteristics of the patients (age, sex, Global Assessment of
      Functioning score, Clinical Global Impression-Severity of Illness score,
      education, occupation, marital status, duration of treatment, and prior treatment
      history), treating psychiatrist experience in years, and sex concordance between
      the patients and their treating psychiatrists were analyzed using Cox regression
      models. RESULTS: From among 1,626 eligible new patients during the study period,
      532 patients were enrolled in the study (F3: n=176; F4: n=356). The dropout rate
      was 35.7%, which was similar to that of previous studies. Higher educational
      level, being married, and lower Global Assessment of Functioning scores were
      associated with a lower dropout rate. Although psychiatrist experience was not
      significantly associated with patient dropout in the multivariate analysis,
      patients treated by less experienced psychiatrists had a higher hazard ratio for
      dropout (1.31; 95% confidence interval: 0.94-1.85). CONCLUSION: In order to
      reduce the dropout rate, special focus should be placed on patients with the
      factors identified in this study, and young psychiatrists should undergo further
      education to foster adherence.

PMID- 27703336
TI  - Profile of the capsaicin 8% patch for the management of neuropathic pain
      associated with postherpetic neuralgia: safety, efficacy, and patient
      acceptability.
AB  - Capsaicin is a naturally occurring irritant active ingredient found in hot
      peppers. It is a ligand for transient receptor potential channel vanilloid
      receptors, which are found in nociceptive nerve terminals in the skin. Initial
      exposure to topical capsaicin leads to excitation of these receptors, release of
      vasoactive mediators, erythema, intense burning, pain, and thereafter
      desensitization of sensory neurons resulting in inhibition of pain transmission.
      Capsaicin 8% has been licensed for the treatment of postherpetic neuralgia pain
      in recent years. A single application of high-concentration capsaicin for 60
      minutes for postherpetic neuralgia has been robustly evaluated. Capsaicin 8%
      patches are applied to the most painful areas of healthy skin and allowed to
      remain for 60 minutes. Treatment can be repeated every 90 days if the pain
      persists or returns. The patches are usually applied in specialist pain clinics
      where patients can be pretreated and monitored. Health care staff need to take
      certain precautions before administering these patches to avoid unintentional
      contact. Common adverse effects of the capsaicin 8% patch are transient mild-to
      moderate self-limiting application-site burning, pain, erythema, pruritus,
      papules, swelling, dryness, and hypertension. To manage local pain from capsaicin
      application, the skin is pretreated with a local anesthetic such as topical
      lidocaine or an oral analgesic such as oxycodone for up to 5 days. A transient
      increase in pain is usually seen within 48 hours of patch application before the
      pain-relieving effect starts. Systemic absorption is minimal and clinically
      insignificant. The nature of administration and relatively high cost of capsaicin
      patches can significantly limit their use to a small number of patients with
      severe refractory symptoms. This review highlights recent evidence related to the
      use and effectiveness of the 8% capsaicin patch for Postherpetic Neuralgia and
      discusses its safety and side-effect profiles.

PMID- 27703337
TI  - Patient expectations and their satisfaction in the context of public hospitals.
AB  - BACKGROUND: Patient expectations have been recognized as a factor for patient
      satisfaction in medical consultations. Although various studies explored the
      relationship between patient expectations and patient satisfaction in developed
      countries, there is a lack of research evidence in Ethiopia where the meeting of
      patient expectations could relate to satisfaction. OBJECTIVE: To assess the
      relationship between patients' expectations and their satisfaction in the
      consultation of patients at the outpatient department. STUDY DESIGN: Data were
      collected regarding preconsultation expectations and postconsultation experiences
      of adult patients attending nine public hospitals. A systematic random sampling
      method was used where every fifth patient attending an outpatient department was
      selected. The patients were interviewed before consultation and after
      consultation to assess whether their pre-consultation expectations were met and
      to assess how satisfied they were with the consultation. Cronbach's alpha
      statistic was used to assess the reliability of the expectation questionnaires,
      and paired t-test was used to assess any differences between previsit
      expectations and postvisit experiences. Logistic regression techniques were used
      to assess variables considered as independent factors for patient satisfaction.
      RESULTS: A total of 776 patients were interviewed, giving a response rate of
      92.3%. About 93.7% mentioned a diagnosis for their condition as a reason for
      their current hospital visits. There is a significant difference between
      preconsultation expectation and postconsultation expectation. Postconsultation
      expectation, perceived health status, and perceived control on health were
      factors identified as increasing patient satisfaction. In addition, the presence
      of any disappointments or worries, previous experience in health care, and extent
      of influence on the consultation had a negative influence on satisfaction.
      CONCLUSION: Postconsultation expectation impacts patient satisfaction. Health
      care service providers should emphasize the actual experience of consultation.

PMID- 27703338
TI  - Development and application of culturally appropriate decision aids for smoking
      cessation in Korea: a pragmatic clustered randomization crossover trial.
AB  - INTRODUCTION: In Asian countries, reluctance to seek pharmacological intervention
      is a major barrier for smoking cessation. Culturally appropriate decision aids
      are expected to help people in the decision making for the use of smoking
      cessation medication. OBJECTIVE: The aim of this study was to develop a
      culturally tailored decision aid for smoking cessation and evaluate its effect on
      the use of smoking cessation medication. PATIENTS AND METHODS: A 7-minute video
      on smoking cessation information and options was developed. Physicians were
      randomized into intervention and control groups. The decision aid was provided to
      patients in the intervention group, and they watched it, while those in the
      control group were provided usual medical care for smoking cessation. The primary
      outcome was the proportion of smokers who were prescribed smoking cessation
      medication within 1 month after consultation. The secondary outcomes were
      abstinence rate and use of smoking cessation medication within 6 months. A
      logistic regression analysis was used to assess the effect of the decision aid on
      the outcomes. RESULTS: In total, 414 current smokers (intervention group: 195;
      control group: 219) were enrolled. The mean age of the participants was 48.2
      years, and 381 subjects (92%) were males. In total, 11.8% of the participants in
      the intervention group and 10.5% in the control group were prescribed smoking
      cessation medications within 1 month. The odds ratio was 1.02 (95% CI: 0.40-2.63)
      after adjustment for baseline characteristics. Within 6 months, 17.4% of the
      participants in the intervention group and 15% in the control group were
      prescribed medication (adjusted odds ratio 1.12, 95% CI: 0.59-2.13). CONCLUSION:
      The culturally tailored smoking cessation decision aid developed in this study
      did not show a significant impact on the decision to use smoking cessation
      medication. Further research to develop more effective and more interactive
      interventions is expected.

PMID- 27703339
TI  - Characteristics of and outcomes for elderly patients with acute myocardial
      infarction: differences between females and males.
AB  - OBJECTIVES: This study analyzed age-adjusted sex differences among acute
      myocardial infarction (AMI) patients aged 75 years and above with regard to 7
      year mortality (primary end point) and the frequency of angiograms and admission
      to the coronary care unit (CCU) as well as 1-year mortality (secondary end
      points). METHODS: A retrospective cohort study comprised 1,414 AMI patients (748
      females and 666 males) aged at least 75 years, who were admitted to Sahlgrenska
      University Hospital in Gothenburg, Sweden, during two periods (2001/2002 and
      2007). All comparisons between female and male patients were age adjusted.
      RESULTS: Females were older and their previous history included fewer AMIs,
      coronary artery bypass grafting procedures, and renal diseases, but more frequent
      incidence of hypertension. On the contrary, males had higher age-adjusted 7-year
      mortality in relation to females (hazard ratio [HR] 1.16 with corresponding 95%
      confidence interval [95% CI 1.03, 1.31], P=0.02). Admission to the CCU was more
      frequent among males than females (odds ratio [OR] 1.38 [95% CI 1.11, 1.72],
      P=0.004). There was a nonsignificant trend toward more coronary angiographies
      performed among males (OR 1.34 [95% CI 1.00, 1.79], P=0.05), as well as a
      nonsignificant trend toward higher 1-year mortality (HR 1.18 [95% CI 0.99, 1.39],
      P=0.06). CONCLUSION: In an AMI population aged 75 years and above, males had
      higher age-adjusted 7-year mortality and higher rate of admission to the CCU than
      females. One-year mortality did not differ significantly between the sexes, nor
      did the frequency of performed coronary angiograms.

PMID- 27703341
TI  - Cost-effectiveness and budget impact of the fixed-dose dual bronchodilator
      combination tiotropium-olodaterol for patients with COPD in the Netherlands.
AB  - PURPOSE: The fixed-dose dual bronchodilator combination (FDC) of tiotropium and
      olodaterol showed increased effectiveness regarding lung function and health
      related quality of life in patients with chronic obstructive pulmonary disease
      (COPD) compared with the use of its mono-components. Yet, while effectiveness and
      safety have been shown, the health economic implication of this treatment is
      still unknown. The aim of this study was to assess the cost-utility and budget
      impact of tiotropium-olodaterol FDC in patients with moderate to very severe COPD
      in the Netherlands. PATIENTS AND METHODS: A cost-utility study was performed,
      using an individual-level Markov model. To populate the model, individual patient
      level data (age, height, sex, COPD duration, baseline forced expiratory volume in
      1 second) were obtained from the tiotropium-olodaterol TOnado trial. In the
      model, forced expiratory volume in 1 second and patient-level data were
      extrapolated to utility and survival, and treatment with tiotropium-olodaterol
      FDC was compared with tiotropium. Cost-utility analysis was performed from the
      Dutch health care payer's perspective using a 15-year time horizon in the base
      case analysis. The standard Dutch discount rates were applied (costs: 4.0%;
      effects: 1.5%). Both univariate and probabilistic sensitivity analyses were
      performed. Budget impact was annually assessed over a 5-year time horizon, taking
      into account different levels of medication adherence. RESULTS: As a result of
      cost increases, combined with quality-adjusted life-year (QALY) gains, results
      showed that tiotropium-olodaterol FDC had an incremental cost-effectiveness ratio
      of ?7,004/QALY. Without discounting, the incremental cost-effectiveness ratio was
      ?5,981/QALY. Results were robust in univariate and probabilistic sensitivity
      analyses. Budget impact was estimated at ?4.3 million over 5 years assuming 100%
      medication adherence. Scenarios with 40%, 60%, and 80% adherence resulted in
      lower 5-year incremental cost increases of ?1.7, ?2.6, and ?3.4 million,
      respectively. CONCLUSION: Tiotropium-olodaterol FDC can be considered a cost
      effective treatment under current Dutch cost-effectiveness thresholds.

PMID- 27703340
TI  - A concise review of testosterone and bone health.
AB  - Osteoporosis is a condition causing significant morbidity and mortality in the
      elderly population worldwide. Age-related testosterone deficiency is the most
      important factor of bone loss in elderly men. Androgen can influence bone health
      by binding to androgen receptors directly or to estrogen receptors (ERs)
      indirectly via aromatization to estrogen. This review summarized the direct and
      indirect effects of androgens on bone derived from in vitro, in vivo, and human
      studies. Cellular studies showed that androgen stimulated the proliferation of
      preosteoblasts and differentiation of osteoblasts. The converted estrogen
      suppressed osteoclast formation and resorption activity by blocking the receptor
      activator of nuclear factor k-B ligand pathway. In animal studies, activation of
      androgen and ERalpha, but not ERbeta, was shown to be important in acquisition
      and maintenance of bone mass. Human epidemiological studies demonstrated a
      significant relationship between estrogen and testosterone in bone mineral
      density and fracture risk, but the relative significance between the two remained
      debatable. Human experimental studies showed that estrogen was needed in
      suppressing bone resorption, but both androgen and estrogen were indispensable
      for bone formation. As a conclusion, maintaining optimal level of androgen is
      essential in preventing osteoporosis and its complications in elderly men.

PMID- 27703342
TI  - Chronic Pseudomonas aeruginosa infection-induced chronic bronchitis and
      emphysematous changes in CCSP-deficient mice.
AB  - The club cell secretory protein (CCSP) is a regulator of lung inflammation
      following acute respiratory infection or lung injury. Recently, the relationship
      between CCSP and COPD has been reported. Since COPD results from an abnormal
      inflammatory response, we hypothesized that CCSP could have a protective role
      against chronic inflammation-induced lung damage. To address this issue, the
      pathophysiology of chronic lung inflammation induced by Pseudomonas aeruginosa in
      CCSP-deficient mice was determined. A tube of 5 mm in length was soaked in a
      fluid containing P. aeruginosa (PAO01 strain) for 1 week and inserted into the
      trachea of CCSP-deficient mice. One week later, P. aeruginosa was administered
      into the trachea. Five weeks after insertion of tube, the mice were sacrificed.
      Bronchoalveolar lavage fluids were collected to determine the bacterial growth,
      and the lung histology and physiology were also examined. P. aeruginosa was
      continuously detected in bronchoalveolar lavage fluids during the study.
      Neutrophils were increased in the bronchoalveolar lavage fluids from the CCSP
      deficient mice in comparison to wild-type mice. A histological study demonstrated
      chronic inflammation around bronchus, serious bronchial stenosis, and alveolar
      enlargement in the CCSP-deficient mice. The lung physiology study demonstrated an
      increase in the lung compliance of the CCSP-deficient mice. Chronic P. aeruginosa
      inflammation resulted in chronic bronchitis and emphysematous changes in the CCSP
      deficient mice. CCSP could play an important role in protecting the host from the
      chronic inflammation-induced lung damage.

PMID- 27703343
TI  - Mortality associated with bone fractures in COPD patients.
AB  - BACKGROUND AND OBJECTIVE: COPD is well known to frequently coexist with
      osteoporosis. Bone fractures often occur and may affect mortality in COPD
      patients. However, in-hospital mortality related to bone fractures in COPD
      patients has been poorly studied. This retrospective study investigated in
      hospital mortality of COPD patients with bone fractures using a national
      inpatient database in Japan. METHODS: Data of COPD patients admitted with bone
      fractures, including hip, vertebra, shoulder, and forearm fractures to 1,165
      hospitals in Japan between July 2010 and March 2013, were extracted from the
      Diagnosis Procedure Combination database. The clinical characteristics and
      mortalities of the patients were determined. Multivariable logistic regression
      analysis was also performed to determine the factors associated with in-hospital
      mortality of COPD patients with hip fractures. RESULTS: Among 5,975 eligible
      patients, those with hip fractures (n=4,059) were older, had lower body mass
      index (BMI), and had poorer general condition than those with vertebral
      (n=1,477), shoulder (n=281), or forearm (n=158) fractures. In-hospital mortality
      was 7.4%, 5.2%, 3.9%, and 1.3%, respectively. Among the hip fracture group,
      surgical treatment was significantly associated with lower mortality (adjusted
      odds ratio, 0.43; 95% confidence interval, 0.32-0.56) after adjustment for
      patient backgrounds. Higher in-hospital mortality was associated with male sex,
      lower BMI, lower level of consciousness, and having several comorbidities,
      including pneumonia, lung cancer, congestive heart failure, chronic liver
      disease, and chronic renal failure. CONCLUSION: COPD patients with hip fractures
      had higher mortality than COPD patients with other types of fracture. Surgery for
      hip fracture was associated with lower mortality than conservative treatment.

PMID- 27703344
TI  - Effectiveness using higher inhaled corticosteroid dosage in patients with COPD by
      different blood eosinophilic counts.
AB  - BACKGROUND: Blood eosinophil counts have been documented as a good biomarker for
      patients with chronic obstructive pulmonary disease (COPD) using inhaled
      corticosteroid (ICS) therapy. However, the effectiveness and safety of
      prescribing high or medium dose of ICS for patients with different eosinophil
      counts are unknown. METHODS: A post hoc analysis of a previous prospective
      randomized study was performed for COPD patients using higher dose (HD:
      Fluticasone 1,000 MUg/day) or medium dose (MD: Fluticasone 500 MUg/day) of ICS
      combined with Salmeterol (100 MUg/day). Patients were classified into two groups:
      those with high eosinophil counts (HE >=3%) and those with low eosinophil counts
      (LE <3%). Lung function was evaluated with forced expiratory volume in 1 second,
      forced vital capacity, and COPD assessment test. Frequencies of acute
      exacerbation and pneumonia were also measured. RESULTS: Two hundred and forty
      eight patients were studied and classified into higher eosinophil (HE) (n=85,
      34.3%) and lower eosinophil (LE) groups (n=163, 65.7%). The levels of forced
      expiratory volume in 1 second were significantly increased in patients of HE
      group treated with HD therapy, compared with the other groups (HE/HD: 125.9+/
      27.2 mL vs HE/MD: 94.3+/-23.7 mL, vs LE/HD: 70.4+/-20.5 mL, vs LE/MD: 49.8+/-16.7
      mL; P<0.05) at the end of the study. Quality of life (COPD assessment test)
      markedly improved in HE/HD group than in MD/LE group (HE/HD: 9+/-5 vs LE/MD: 16+/
      7, P=0.02). The frequency of acute exacerbation was more decreased in HE/HD group
      patients, compared with that in LE/MD group (HE/HD: 13.5% vs LE/MD: 28.7%,
      P<0.01). Pneumonia incidence was similar in the treatment groups (HE/HD: 3.2%,
      HE/MD: 2.6%, LE/HD: 3.5%, LE/MD 2.8%; P=0.38). CONCLUSION: The study results
      support using blood eosinophil counts as a biomarker of ICS response and show the
      benefits of greater improvement of lung function, quality of life, and decreased
      exacerbation frequency in COPD patients with blood eosinophil counts higher than
      3%, especially treated with higher dose of ICS.

PMID- 27703345
TI  - Impaired training-induced adaptation of blood pressure in COPD patients:
      implication of the muscle capillary bed.
AB  - BACKGROUND AND AIMS: Targeting the early mechanisms in exercise-induced arterial
      hypertension (which precedes resting arterial hypertension in its natural
      history) may improve cardiovascular morbidity and mortality in COPD patients.
      Capillary rarefaction, an early event in COPD before vascular remodeling, is a
      potential mechanism of exercise-induced and resting arterial hypertension.
      Impaired training-induced capillarization was observed earlier in COPD patients;
      thus, this study compares the changes in blood pressure (BP) during exercise in
      COPD patients and matches control subjects (CSs) after a similar exercise
      training program, in relationship with muscle capillarization. METHODS: Resting
      and maximal exercise diastolic pressure (DP) and systolic pressure (SP) were
      recorded during a standardized cardiopulmonary exercise test, and a quadriceps
      muscle biopsy was performed before and after training. RESULTS: A total of 35 CSs
      and 49 COPD patients (forced expiratory volume in 1 second =54%+/-22% predicted)
      completed a 6-week rehabilitation program and improved their symptom-limited
      maximal oxygen uptake (VO2SL: 25.8+/-6.1 mL/kg per minute vs 27.9 mL/kg per
      minute and 17.0+/-4.7 mL/kg per minute vs 18.3 mL/kg per minute; both P<0.001).
      The improvement in muscle capillary-to-fiber (C/F) ratio was significantly
      greater in CSs vs COPD patients (+11%+/-9% vs +23%+/-21%; P<0.05). Although
      maximal exercise BP was reduced in CSs (DP: 89+/-10 mmHg vs 85+/-9 mmHg;
      P<0.001/SP: 204+/-25 mmHg vs 196+/-27 mmHg; P<0.05), it did not change in COPD
      patients (DP: 94+/-14 mmHg vs 97+/-16 mmHg; P=0.46/SP: 202+/-27 mmHg vs 208+/-24
      mmHg; P=0.13). The change in muscle C/F ratio was negatively correlated with
      maximal exercise SP in CSs and COPD patients (r=-0.41; P=0.02). CONCLUSION: COPD
      patients showed impaired training-induced BP adaptation related to a change in
      muscle capillarization, suggesting the possibility of blunted angiogenesis.

PMID- 27703346
TI  - Inhaled corticosteroid normalizes some but not all airway vascular remodeling in
      COPD.
AB  - BACKGROUND: This study assessed the effects of inhaled corticosteroid (ICS) on
      airway vascular remodeling in chronic obstructive pulmonary disease (COPD).
      METHODS: Thirty-four subjects with mild-to-moderate COPD were randomly allocated
      2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months.
      Available tissue was compared before and after treatment for vessel density, and
      expression of VEGF, TGF-beta1, and TGF-beta1-related phosphorylated transcription
      factors p-SMAD 2/3. This clinical trial has been registered and allocated with
      the Australian New Zealand Clinical Trials Registry (ANZCTR) on 17/10/2012 with
      reference number ACTRN12612001111864. RESULTS: There were no significant baseline
      differences between treatment groups. With ICS, vessels and angiogenic factors
      did not change in hypervascular reticular basement membrane, but in the
      hypovascular lamina propria (LP), vessels increased and this had a proportionate
      effect on lung air trapping. There was modest evidence for a reduction in LP
      vessels staining for VEGF with ICS treatment, but a marked and significant
      reduction in p-SMAD 2/3 expression. CONCLUSION: Six-month high-dose ICS treatment
      had little effect on hypervascularity or angiogenic growth factors in the
      reticular basement membrane in COPD, but normalized hypovascularity in the LP,
      and this was physiologically relevant, though accompanied by a paradoxical
      reduction in growth factor expression.

PMID- 27703347
TI  - Microstructural, spectroscopic, and antibacterial properties of silver-based
      hybrid nanostructures biosynthesized using extracts of coriander leaves and
      seeds.
AB  - Coriander leaves and seeds have been highly appreciated since ancient times, not
      only due to their pleasant flavors but also due to their inhibitory activity on
      food degradation and their beneficial properties for health, both ascribed to
      their strong antioxidant activity. Recently, it has been shown that coriander
      leaf extracts can mediate the synthesis of metallic nanoparticles through
      oxidation/reduction reactions. In the present study, extracts of coriander leaves
      and seeds have been used as reaction media for the wet chemical synthesis of
      ultrafine silver nanoparticles and nanoparticle clusters, with urchin- and tree
      like shapes, coated by biomolecules (mainly, proteins and polyphenols). In this
      greener route of nanostructure preparation, the active biocompounds of coriander
      simultaneously play the roles of reducing and stabilizing agents. The
      morphological and microstructural studies of the resulting biosynthesized silver
      nanostructures revealed that the nanostructures prepared with a small
      concentration of the precursor Ag salt (AgNO3 =5 mM) exhibit an ultrafine size
      and a narrow size distribution, whereas particles synthesized with high
      concentrations of the precursor Ag salt (AgNO3 =0.5 M) are polydisperse and
      formation of supramolecular structures occurs. Fourier transform infrared and
      Raman spectroscopy studies indicated that the bioreduction of the Ag- ions takes
      place through their interactions with free amines, carboxylate ions, and hydroxyl
      groups. As a consequence of such interactions, residues of proteins and
      polyphenols cap the biosynthesized Ag nanoparticles providing them a hybrid
      core/shell structure. In addition, these biosynthesized Ag nanomaterials
      exhibited size-dependent plasmon extinction bands and enhanced bactericidal
      activities against both Gram-positive and Gram-negative bacteria, displaying
      minimal inhibitory Ag concentrations lower than typical values reported in the
      literature for Ag nanoparticles, probably due to the synergy of the bactericidal
      activities of the Ag nanoparticle cores and their capping ligands.

PMID- 27703348
TI  - Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles
      for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo
      studies.
AB  - Recently, research has progressively highlighted on clues from conventional use
      of herbal medicines to introduce new anticancer drugs. Aloe-emodin (AE) is a
      herbal drug with promising anticancer activity. Nevertheless, its clinical
      utility is handicapped by its low solubility. For the first time, this study aims
      to the fabrication of surface-functionalized polyethylene glycol liquid
      crystalline nanoparticles (PEG-LCNPs) of AE to enhance its water solubility and
      enable its anticancer use. Developed AE-PEG-LCNPs were optimized via particle
      size and zeta potential measurements. Phase behavior, solid state
      characteristics, hemocompatibility, and serum stability of LCNPs were assessed.
      Sterile formulations were developed using various sterilization technologies.
      Furthermore, the potential of the formulations was investigated using cell
      culture, pharmacokinetics, biodistribution, and toxicity studies. AE-PEG-LCNPs
      showed particle size of 190 nm and zeta potential of -49.9, and PEGylation
      approach reduced the monoolein hemolytic tendency to 3% and increased the serum
      stability of the nanoparticles. Sterilization of liquid and lyophilized AE-PEG
      LCNPs via autoclaving and gamma-radiations, respectively, insignificantly
      affected the physicochemical properties of the nanoparticles. Half maximal
      inhibitory concentration of AE-PEG-LCNPs was 3.6-fold lower than free AE after 48
      hours and their cellular uptake was threefold higher than free AE after 24-hour
      incubation. AE-PEG-LCNPs presented 5.4-fold increase in t1/2 compared with free
      AE. Biodistribution and toxicity studies showed reduced AE-PEG-LCNP uptake by
      reticuloendothelial system organs and good safety profile. PEGylated LCNPs could
      serve as a promising nanocarrier for efficient delivery of AE to cancerous cells.

PMID- 27703350
TI  - Viruses as nanomedicine for cancer.
AB  - Oncolytic virotherapy, a type of nanomedicine in which oncolytic viruses (OVs)
      are used to selectively infect and lyse cancer cells, is an emerging field in
      cancer therapy. Some OVs exhibit a specific tropism for cancer cells, whereas
      others require genetic modification to enhance their binding with and entry into
      cancer cells. OVs both kill tumor cells and induce the host's immune response
      against tumor cells. Armed with antitumor cellular molecules, antibodies, and/or
      in combination with anticancer drugs, OVs can accelerate the lysis of cancer
      cells. Among the OVs, vaccinia virus has been the focus of preclinical and
      clinical research because of its many favorable properties. In this review, the
      basic mechanisms of action of OVs are presented, including their entry, survival,
      tumor lysis, and immune activation, and the latest research in vaccinia virus
      based virotherapy and its status as an anticancer nanomedicine in prospective
      clinical trials are discussed.

PMID- 27703349
TI  - TiO2 nanotube platforms for smart drug delivery: a review.
AB  - Titania nanotube (TNT) arrays are recognized as promising materials for localized
      drug delivery implants because of their excellent properties and facile
      preparation process. This review highlights the concept of localized drug
      delivery systems based on TNTs, considering their outstanding biocompatibility in
      a series of ex vivo and in vivo studies. Considering the safety of TNT implants
      in the host body, studies of the biocompatibility present significant importance
      for the clinical application of TNT implants. Toward smart TNT platforms for
      sustainable drug delivery, several advanced approaches were presented in this
      review, including controlled release triggered by temperature, light,
      radiofrequency magnetism, and ultrasonic stimulation. Moreover, TNT implants used
      in medical therapy have been demonstrated by various examples including
      dentistry, orthopedic implants, cardiovascular stents, and so on. Finally, a
      future perspective of TNTs for clinical applications is provided.

PMID- 27703351
TI  - Treatment of natural mammary gland tumors in canines and felines using gold
      nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis.
AB  - Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods
      are injected at the site of a tumor before near-infrared light is transiently
      applied to the tumor causing localized cell death. Previously, PPTT studies have
      been carried out on xenograft mice models. Herein, we report a study showing the
      feasibility of PPTT as applied to natural tumors in the mammary glands of dogs
      and cats, which more realistically represent their human equivalents at the
      molecular level. We optimized a regime of three low PPTT doses at 2-week
      intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland
      tumors from seven animals. Histopathology, X-ray, blood profiles, and
      comprehensive examinations were used for both the diagnosis and the evaluation of
      tumor statuses before and after treatment. Histopathology results showed an
      obvious reduction in the cancer grade shortly after the first treatment and a
      complete regression after the third treatment. Blood tests showed no obvious
      change in liver and kidney functions. Similarly, X-ray diffraction showed no
      metastasis after 1 year of treatment. In conclusion, our study suggests the
      feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats
      without any relapse or toxicity effects after 1 year of treatment.

PMID- 27703353
TI  - Splitting, impulsivity, and intimate partnerships in young obese women seeking
      bariatric treatment.
AB  - BACKGROUND: Splitting represents a defense mechanism that describes fragmentation
      of conscious experience that may occur in various psychopathological conditions.
      The purpose of this study was to examine the relationship of splitting with
      disturbed cognitive and affective functions related to impulsivity and intimate
      partnerships in a group of obese patients indicated for bariatric treatment and
      compare the results with other obese patients and patients with bulimia nervosa.
      METHODS: In this clinical study, we assessed 102 young women. The sample was
      divided into three subgroups: obese women (N=30), obese women indicated for
      bariatric treatment (N=48), and patients with bulimia nervosa (N=24). The
      patients were assessed using Splitting Index and Barratt Impulsivity Scale, and
      selected information about their intimate partnership was documented for all the
      participants. RESULTS: The main results of this study indicate significant
      differences in the relationship of splitting and impulsivity with difficulties in
      intimate partnerships. These differences discriminate obese patients indicated
      for bariatric treatment from other obese patients and patients with bulimia
      nervosa. CONCLUSION: These findings may have significant implications for
      treatment of the obese patients indicated for bariatric treatment and their
      presurgery psychological evaluations.

PMID- 27703352
TI  - Multimodal near-infrared-emitting PluS Silica nanoparticles with fluorescent,
      photoacoustic, and photothermal capabilities.
AB  - PURPOSE: The aim of the present study was to develop nanoprobes with theranostic
      features, including - at the same time - photoacoustic, near-infrared (NIR)
      optical imaging, and photothermal properties, in a versatile and stable core
      shell silica-polyethylene glycol (PEG) nanoparticle architecture. MATERIALS AND
      METHODS: We synthesized core-shell silica-PEG nanoparticles by a one-pot direct
      micelles approach. Fluorescence emission and photoacoustic and photothermal
      properties were obtained at the same time by appropriate doping with
      triethoxysilane-derivatized cyanine 5.5 (Cy5.5) and cyanine 7 (Cy7) dyes. The
      performances of these nanoprobes were measured in vitro, using nanoparticle
      suspensions in phosphate-buffered saline and blood, dedicated phantoms, and after
      incubation with MDA-MB-231 cells. RESULTS: We obtained core-shell silica-PEG
      nanoparticles endowed with very high colloidal stability in water and in
      biological environment, with absorption and fluorescence emission in the NIR
      field. The presence of Cy5.5 and Cy7 dyes made it possible to reach a more
      reproducible and higher doping regime, producing fluorescence emission at a
      single excitation wavelength in two different channels, owing to the energy
      transfer processes within the nanoparticle. The nanoarchitecture and the presence
      of both Cy5.5 and Cy7 dyes provided a favorable agreement between fluorescence
      emission and quenching, to achieve optical imaging and photoacoustic and
      photothermal properties. CONCLUSION: We obtained rationally designed
      nanoparticles with outstanding stability in biological environment. At
      appropriate doping regimes, the presence of Cy5.5 and Cy7 dyes allowed us to tune
      fluorescence emission in the NIR for optical imaging and to exploit quenching
      processes for photoacoustic and photothermal capabilities. These nanostructures
      are promising in vivo theranostic tools for the near future.

PMID- 27703354
TI  - The role of augmentative and alternative communication for children with autism:
      current status and future trends.
AB  - BACKGROUND: Augmentative and alternative communication (AAC) interventions are
      used for children with autism, often as stand-alone communication interventions
      for those who are minimally verbal. Our aim was to synthesize the evidence for
      AAC interventions for children (up to 21 years), and then consider the role of
      AAC within established, comprehensive, evidence-based autism interventions
      targeting learning across multiple developmental domains. DESIGN: We completed a
      systematic search of three databases (OVID Medline, PsycINFO, ERIC) as well as
      forward citation and hand searches to identify systematic reviews of AAC
      intervention efficacy research including children with autism, published between
      2000 and March 2016 in peer-reviewed journals. Data pertaining to the quality
      indicators of included studies, effect sizes for intervention outcomes, and
      evidence for effectiveness were extracted for descriptive analysis. RESULTS: The
      search yielded 17 systematic reviews. Most provided indicators of research
      quality for included studies, of which only relatively few provided conclusive
      results. Communication targets tended to be focused on teaching children to make
      requests. Still, effect size measures for included studies indicated that AAC was
      effective to highly effective. CONCLUSION: There is growing evidence for the
      potential benefits of AAC for children with autism, but there is a need for more
      well-designed studies and broader, targeted outcomes. Furthermore, a lack of
      evidence for the role of AAC within comprehensive intervention programs may
      account for a tendency by autism researchers and practitioners to neglect this
      intervention. Attempts to compare evidence for AAC with other interventions for
      children with autism, including those in which the use of AAC is delayed or
      excluded in pursuit of speech-only communication, must take into account the
      needs of children with the most significant learning needs. These children pose
      the greatest challenges to achieving large and consistent intervention effects,
      yet stand to gain the most from AAC interventions.

PMID- 27703355
TI  - Noradrenaline plays a critical role in the switch to a manic episode and
      treatment of a depressive episode.
AB  - Although antidepressants may increase the risk of switching to mania in bipolar
      disorder (BD), clinicians have been using antidepressants to treat patients with
      bipolar depression. Appropriate treatments for bipolar depression remain
      controversial. In BD, antidepressants comprise a double-edged sword in terms of
      their efficacy in treating depression and the increased risk of switching. This
      review presents an important table outlining the benefit in terms of depression
      improvement and the risk of switching in the clinical setting. It also proposes
      strategies based on the characteristics of antidepressants such as their
      pharmacology, specifically the equilibrium dissociation constant (KD) of the
      noradrenaline transporter. This table will be useful for clinicians while
      considering benefit and risk. Antidepressants augmenting noradrenaline may be
      effective in bipolar depression. However, it is easily presumed that such
      antidepressants may also have a risk of switching to mania. Therefore,
      antidepressants augmenting noradrenaline will be the recommended treatment in
      combination with an antimanic agent, or they may be used for short-term treatment
      and early discontinuation. The corresponding medical treatment guidelines
      probably need to be reevaluated and updated based on biological backgrounds. From
      previous studies, we understand that the stability of noradrenaline levels is
      important for BD amelioration, based on the pathophysiology of the disorder. It
      is hoped that researchers will reevaluate BD by conducting studies involving
      noradrenaline.

PMID- 27703357
TI  - Distinctive Rorschach profiles of young adults with schizophrenia and autism
      spectrum disorder.
AB  - OBJECTIVE: The differential diagnosis of schizophrenia (SZ) versus autism
      spectrum disorder (ASD) can be clinically challenging because accumulating
      evidence suggests both clinical and biological overlaps between them. The aim of
      this study was to compare Rorschach profiles between young adults with SZ and
      those with ASD. METHODS: We evaluated quantitative tendencies on the Rorschach
      test among 20 patients diagnosed with SZ and 20 diagnosed with ASD. Both groups
      were matched for age, sex, and intelligence quotient. RESULTS: We found
      significant differences in six response variables on the Rorschach comprehensive
      system. Those with SZ had significantly higher scores on D score, adjusted D
      score (Adj D), developmental quality code reflecting ordinary response (DQo), and
      form quality minus (FQ -) than those with ASD. In contrast, those with SZ had
      significantly lower scores on the active and developmental quality code
      reflecting synthesized response (DQ+) subscales than those with ASD. CONCLUSION:
      The present findings reveal that individuals with SZ might have more stress
      tolerance, stronger perception distortions, and simpler and poorer recognition
      than those with ASD. We suggest that the Rorschach test might be a useful tool
      for differentiating between SZ and ASD.

PMID- 27703358
TI  - miR-370 mimic inhibits replication of Japanese encephalitis virus in glioblastoma
      cells.
AB  - Japanese encephalitis (JE) is one of the most severe viral infections of the
      central nervous system. No effective treatment for JE currently exists, because
      its pathogenesis remains largely unknown. The present study was designed to
      screen the potential microRNAs (miRNAs) involved in JE. Glioblastoma cells were
      collected, after being infected with the Japanese encephalitis virus (JEV). Total
      miRNAs were extracted and analyzed using an miRNA chip. One of the most severely
      affected miRNAs was selected, and the role of miR-370 in JEV infection was
      investigated. Cell viability and apoptosis of the host cells were evaluated. JEV
      replication was detected via analysis of gene E expression. Real-time polymerase
      chain reaction was used to determine the levels of endogenous miR-370 and
      expression of innate immunity-related genes. Following JEV infection, 114 miRNAs
      were affected, as evidenced by the miRNA chip. Among them, 30 miRNAs were
      upregulated and 84 were downregulated. The changes observed in five miRNAs were
      confirmed by real-time polymerase chain reaction. One of the significantly
      downregulated miRNAs was miR-370. Therefore, miR-370 mimic was transfected into
      the cells, following which the levels of endogenous miR-370 were significantly
      elevated. Concurrently, JEV replication was significantly reduced 24 hours after
      transfection of miR-370 mimic. Functionally, miR-370 mimic mitigated both JEV
      induced apoptosis and the inhibition of host cell proliferation. Following JEV
      infection, interferon-beta and nuclear factor-kappa B were upregulated, whereas
      miR-370 mimic prevented the upregulation of the genes induced by JEV infection.
      The present study demonstrated that miR-370 expression in host cells is
      downregulated following JEV infection, which further mediates innate immunity
      related gene expression. Taken together, miR-370 mimic might be useful to prevent
      viral replication and infection-induced host cell injury.

PMID- 27703356
TI  - Nine traditional Chinese herbal formulas for the treatment of depression: an
      ethnopharmacology, phytochemistry, and pharmacology review.
AB  - Depression is a major mental disorder, and is currently recognized as the second
      leading cause of disability worldwide. However, the therapeutic effect of
      antidepressants remains unsatisfactory. For centuries, Chinese herbal formulas
      (CHFs) have been widely used in the treatment of depression, achieving better
      therapeutic effects than placebo and having fewer side effects than conventional
      antidepressants. Here, we review the ethnopharmacology, phytochemistry, and
      pharmacology studies of nine common CHFs: "banxia houpo" decoction, "chaihu
      shugansan", "ganmaidazao" decoction, "kaixinsan", "shuganjieyu" capsules,
      "sinisan", "wuling" capsules, "xiaoyaosan", and "yueju". Eight clinical trials
      and seven meta-analyses have supported the theory that CHFs are effective
      treatments for depression, decreasing Hamilton Depression Scale scores and
      showing few adverse effects. Evidence from 75 preclinical studies has also
      elucidated the multitarget and multipathway mechanisms underlying the
      antidepressant effect of the nine CHFs. Decoctions, capsules, and pills all
      showed antidepressant effects, ranked in descending order of efficacy. According
      to traditional Chinese medicine theory, these CHFs have flexible compatibility
      and mainly act by soothing the liver and relieving depression. This review
      highlights the effective treatment choices and candidate compounds for patients,
      practitioners, and researchers in the field of traditional Chinese medicine. In
      summary, the current evidence supports the efficacy of CHFs in the treatment of
      depression, but additional large-scale randomized controlled clinical trials and
      sophisticated pharmacology studies should be performed.

PMID- 27703359
TI  - Increased frontal electroencephalogram theta amplitude in patients with anorexia
      nervosa compared to healthy controls.
AB  - OBJECTIVE: To conduct a blind study of quantitative electroencephalogram-band
      amplitudes in patients with anorexia nervosa (AN) and healthy controls. METHODS:
      Twenty-one patients with AN and 24 controls were examined with eyes-closed 16
      channel electroencephalogram. Main variables were absolute alpha, theta, and
      delta amplitudes in frontal, temporal, and posterior regions. RESULTS: There were
      no significant differences between the AN patients and controls regarding
      absolute regional band amplitudes in MUV. Borderline significance was found for
      anterior theta (P=0.051). Significantly increased left and right frontal
      electrode theta amplitude was found in AN patients (F3, P=0.014; F4, P=0.038)
      compared to controls. Significant differences were also observed for secondary
      variables: lower values for relative parietooccipital delta and frontocentral
      alpha activity among AN patients than among controls. CONCLUSION: We observed
      slight excess frontal theta and lower relative alpha and delta amplitudes among
      AN patients than among controls. This pattern is possibly related to a slight
      frontal lobe dysfunction in AN, or it may reflect increased attention/vigilance
      or another state-related change in patients with AN compared to healthy controls.

PMID- 27703361
TI  - Mean platelet volume and red cell distribution width levels in initial evaluation
      of panic disorder.
AB  - BACKGROUND: As the relationship between psychological stress and platelet
      activation has been widely studied in recent years, activated platelets lead to
      certain biochemical changes, which occur in the brain in patients with mental
      disorders. However, data relating to the mean platelet volume (MPV) in patients
      with panic disorder (PD) are both limited and controversial. Herein, we aimed to
      evaluate, for the first time, the red cell distribution width (RDW) levels
      combined with MPV levels in patients with PD. PATIENTS AND METHODS: Between
      January 2012 and June 2015, data of 30 treatment-naive patients (16 females, 14
      males; mean age: 37+/-10 years; range: 18-59 years) who were diagnosed with PD
      and 25 age- and sex-matched healthy volunteers (10 females, 15 males; mean age:
      36+/-13 years; range: 18-59 years) (control group) were retrospectively analyzed.
      The white blood cell count (WBC), MPV, and RDW levels were measured in both
      groups. RESULTS: The mean WBC, MPV, and RDW levels were 9,173.03+/-2,400.31/mm3,
      8.19+/-1.13 fl, and 12.47+/-1.14%, respectively, in the PD group. These values
      were found to be 7,090.24+/-1,032.61, 6.85+/-0.67, and 11.63+/-0.85,
      respectively, in the healthy controls. The WBC, MPV, and RDW levels were
      significantly higher in the patients with PD compared to the healthy controls
      (P=0.001, P=0.001, and P=0.003, respectively). However, there was no significant
      difference in the platelet number between the patients with PD and healthy
      controls (P>0.05). CONCLUSION: Our study results are the first to demonstrate
      that the RDW levels combined with MPV levels significantly increase among
      patients with PD. We believe that increased RDW and MPV levels can be used as a
      novel marker for PD.

PMID- 27703360
TI  - Delirium as a complication of the surgical intensive care.
AB  - BACKGROUND: The aim of this study was to examine the impact of somatic illnesses,
      electrolyte imbalance, red blood cell count, hypotension, and antipsychotic and
      opioid treatment on the duration of delirium in Central Intensive Care Unit for
      Surgery. PATIENTS AND METHODS: Patients who were admitted to the Department of
      Central Intensive Care Unit for Surgery in the University Hospital Olomouc from
      February 2004 to November 2008 were evaluated using Riker sedation-agitation
      scale. Their blood pressure, heart rate, respiratory rate, and peripheral blood
      oxygen saturation were measured continually, and body temperature was monitored
      once in an hour. The laboratory blood tests including sodium, potassium,
      chlorides, phosphorus, urea and creatinine, hemoglobin, hematocrit, red and white
      blood cell count, and C-reactive protein, albumin levels and laboratory markers
      of renal and liver dysfunction were done every day. All measurements were made at
      least for ten consecutive days or longer until the delirium resolved. RESULTS:
      The sample consisted of 140 consecutive delirious patients with a mean age of
      68.21+/-12.07 years. Delirium was diagnosed in 140 of 5,642 patients (2.48%)
      admitted in CICUS in the last 5 years. The median duration of delirium was 48
      hours with a range of 12-240 hours. Statistical analysis showed that hyperactive
      subtype of delirium and treatment with antipsychotics were associated with
      prolonged delirium duration (hyperactive 76.15+/-40.53 hours, hypoactive 54.46+/
      28.44 hours, mixed 61.22+/-37.86 hours; Kruskal-Wallis test: 8.022; P<0.05). The
      duration of delirium was significantly correlated also with blood potassium
      levels (Pearson's r=0.2189, P<0.05), hypotension (hypotension 40.41+/-30.23 hours
      versus normotension 70.47+/-54.98 hours; Mann-Whitney U=1,512; P<0.05),
      administration of antipsychotics compared to other drugs (antipsychotics 72.83+/
      40.6, benzodiazepines 42.00+/-20.78, others drugs, mostly piracetam 46.96+/-18.42
      hours; Kruskal-Wallis test: 17.39, P<0.0005), and history of alcohol abuse (with
      a history of abuse 73.63+/-45.20 hours, without a history of abuse 59.54+/-30.61
      hours; Mann-Whitney U=1,840; P<0.05). One patient had suffered from complicated
      postoperative hypostatic pneumonia and died due to respiratory failure (patient
      with hypoactive subtype). According to the backward stepwise multiple regression,
      the best significant predictors of duration of the delirium were the hypotension,
      type of psychopharmacs, type of delirium, the daily dose of opioids, a
      combination of psychopharmacs, history of alcohol abuse, plasma level of
      potassium, anemia, hyperpyrexia, and plasma level of albumin, reaching
      statistical significance (analysis of variance: F=5.205; df=24; P<0.005; adjusted
      r2=0.637). CONCLUSION: The hyperactive type of delirium, hypotension, usage of
      antipsychotics, the higher daily dose of opioids, a combination of
      psychopharmacs, history of alcohol abuse, low blood levels of potassium, anemia,
      hyperpyrexia, and hypoalbuminemia in the CICUS were associated with longer
      duration of delirium.

PMID- 27703363
TI  - Development of psychotic symptoms following ingestion of small quantities of
      alcohol.
AB  - Psychotic symptoms can occur in some clinical conditions related to alcohol, such
      as intoxication, withdrawal, and other alcohol-induced neuropsychiatric
      disorders. Here, we present a case report of a 24-year-old man, without a known
      psychiatric history, who developed brief psychotic symptoms following ingestion
      of small quantities of alcohol repeatedly. To our knowledge, no related previous
      literature regarding this has been reported.

PMID- 27703362
TI  - Self-stigma in borderline personality disorder - cross-sectional comparison with
      schizophrenia spectrum disorder, major depressive disorder, and anxiety
      disorders.
AB  - INTRODUCTION: Self-stigma arises from one's acceptance of societal prejudices and
      is common in psychiatric patients. This investigation compares the self-stigma of
      a sample of patients with borderline personality disorder (BPD), schizophrenia
      spectrum disorder (SCH), major depressive disorder (MDD), bipolar affective
      disorder (BAD), and anxiety disorders (AD) and explores of the self-stigma with
      the subjective and objective measures of the severity of the disorder and
      demographic factors. METHODS: The total of 184 inpatients admitted to the
      psychotherapeutic department diagnosed with BPD, SCH, MDD, BAP, and AD were
      compared on the internalized stigma of mental illness (ISMI) scale. The ISMI
      total score was correlated with the subjective and objective evaluation of the
      disorder severity (clinical global impression), and clinical and demographic
      factors. RESULTS: The self-stigma levels were statistically significantly
      different among the diagnostic groups (BPD 71.15+/-14.74; SCH 63.2+/-13.27; MDD
      64.09+/-12.2; BAD 62.0+/-14.21; AD 57.62+/-15.85; one-way analysis of variance:
      F=8.698, df=183; P<0.005). However after applying the Bonferroni's multiple
      comparison test, the only significant difference was between the BPD patients and
      the patients with AD (P<0.001). Stepwise regression analysis showed that the
      strongest factors connected with the higher level of self-stigma were being
      without partner, the number of hospitalization, and the severity of the disorder.
      CONCLUSION: The BPD patients suffer from a higher level of self-stigma compared
      to patients with AD. In practice, it is necessary to address the reduction of
      self-stigma by using specific treatment strategies, such as cognitive therapy.

PMID- 27703364
TI  - In vitro and in vivo postmarketing surveillance of valsartan, alone or in
      combination with amlodipine or hydrochlorothiazide, among Palestinian
      hypertensive patients.
AB  - OBJECTIVES: The objectives of this study were to evaluate the general quality of
      the most prescribed products of valsartan (VL; alone or in combination) and to
      evaluate their efficacy and safety among Palestinian population through in vivo
      postmarketing surveillance. PATIENTS AND METHODS: The first part was
      pharmacopeial quality control assay, including dissolution, disintegration,
      friability, and weight uniformity for VL. The second part was a 3-month
      cardiology clinics, observational, postmarketing surveillance pilot study that
      included 103 hypertensive patients who were prescribed 80 mg or 160 mg of VL as
      monotherapy or combination therapy. The end points were reduction in blood
      pressure (BP) and the rate of incidence of adverse effects (AEs) at weeks 4 and
      8. RESULTS: According to our quality control tests, all VL products showed high
      quality standards according to the international guidelines. A reduction in BP
      was observed at weeks 4 and 8, and no significant difference was observed between
      the strengths of 80 mg and 160 mg. Higher BP reduction was observed after the use
      of combination therapy. Moreover, VL was well tolerated; most of the AEs were of
      mild-to-moderate intensity. In general, the most frequently reported AEs included
      headache (17.5%), dizziness (11.75%), and weakness (11.7%). No serious AEs or
      death cases were reported during the study period. CONCLUSION: High quality of VL
      tablet products was used; hence, the observed efficacy and safety results should
      be related to patient's factors and not due to any product defects or substandard
      quality. Moreover, VL is an effective treatment for essential hypertension.

PMID- 27703365
TI  - Long-term safety of tiotropium delivered by Respimat(r) SoftMistTM Inhaler:
      patient selection and special considerations.
AB  - Tiotropium bromide is a long-acting inhaled muscarinic antagonist used in
      patients with chronic respiratory disease. It has been available since 2002 as a
      single-dose dry powder formulation via the HandiHaler(r) dry powder inhaler (DPI)
      device, and since 2007 as the Respimat(r) SoftMistTM Inhaler (SMI). The latter is
      a novel method of medication delivery that utilizes a multidose aqueous solution
      to deliver the drug as a fine mist. Potential benefits include more efficient
      drug deposition throughout the respiratory tract, reduced systemic exposure, and
      greater ease of use and patient satisfaction compared with the use of HandiHaler
      DPI. Although tiotropium bromide delivered via the HandiHaler DPI has been
      clearly shown to improve lung function, dyspnea, and quality of life and to
      reduce exacerbations in patients with chronic obstructive pulmonary disease
      (COPD), there is accumulating evidence regarding the use of tiotropium HandiHaler
      in other respiratory diseases characterized by airflow limitation, such as asthma
      and cystic fibrosis. Developed more recently, tiotropium delivered via the
      Respimat SMI appears to have a similar efficacy and safety profile to the
      HandiHaler DPI, and early data raising the possibility of safety concerns with
      its use in COPD have been refuted by more recent evidence. The benefits over the
      HandiHaler DPI, however, remain unclear. This paper will review the evidence for
      tiotropium delivered via the Respimat SMI inhaler, in particular as an
      alternative to the HandiHaler DPI, and will focus on the safety profile for each
      of the chronic lung diseases in which it has been trialed, as well as an approach
      to appropriate patient selection.

PMID- 27703366
TI  - Clinical, pathological, and radiological characteristics of solitary ground-glass
      opacity lung nodules on high-resolution computed tomography.
AB  - BACKGROUND: Lung nodules are being detected at an increasing rate year by year
      with high-resolution computed tomography (HRCT) being widely used. Ground-glass
      opacity nodule is one of the special types of pulmonary nodules that is confirmed
      to be closely associated with early stage of lung cancer. Very little is known
      about solitary ground-glass opacity nodules (SGGNs). In this study, we analyzed
      the clinical, pathological, and radiological characteristics of SGGNs on HRCT.
      METHODS: A total of 95 resected SGGNs were evaluated with HRCT scan. The
      clinical, pathological, and radiological characteristics of these cases were
      analyzed. RESULTS: Eighty-one adenocarcinoma and 14 benign nodules were observed.
      The nodules included 12 (15%) adenocarcinoma in situ (AIS), 14 (17%) minimally
      invasive adenocarcinoma (MIA), and 55 (68%) invasive adenocarcinoma (IA). No
      patients with recurrence till date have been identified. The positive expression
      rates of anaplastic lymphoma kinase and ROS-1 (proto-oncogene tyrosine-protein
      kinase ROS) were only 2.5% and 8.6%, respectively. The specificity and accuracy
      of HRCT of invasive lung adenocarcinoma were 85.2% and 87.4%. The standard uptake
      values of only two patients determined by 18F-FDG positron emission
      tomography/computed tomography (PET/CT) were above 2.5. The size, density, shape,
      and pleural tag of nodules were significant factors that differentiated IA from
      AIS and MIA. Moreover, the size, shape, margin, pleural tag, vascular cluster,
      bubble-like sign, and air bronchogram of nodules were significant determinants
      for mixed ground-glass opacity nodules (all P<0.05). CONCLUSION: We analyzed the
      clinical, pathological, and radiological characteristics of SGGNs on HRCT and
      found that the size, density, shape, and pleural tag of SGGNs on HRCT are found
      to be the determinant factors of IA. In conclusion, detection of anaplastic
      lymphoma kinase expression and performance of PET/CT scan are not routinely
      recommended.

PMID- 27703368
TI  - Postherpetic neuralgia: epidemiology, pathophysiology, and pain management
      pharmacology.
AB  - Herpes zoster, also known as shingles, is a distinctive clinical condition caused
      by the reactivation of latent varicella zoster (chickenpox) virus following an
      initial infection. Approximately 1 million cases of herpes zoster occur annually
      in the US, and one in every three people develops herpes zoster during their
      lifetime. Postherpetic neuralgia is a neuropathic pain syndrome characterized by
      pain that persists for months to years after resolution of the herpes zoster
      rash. It stems from damage to peripheral and central neurons that may be a
      byproduct of the immune/inflammatory response accompanying varicella zoster virus
      reactivation. Patients with postherpetic neuralgia report decreased quality of
      life and interference with activities of daily living. Approaches to management
      of postherpetic neuralgia include preventing herpes zoster through vaccination
      and/or antiviral treatment, and administering specific medications to treat pain.
      Current guidelines recommend treatment of postherpetic neuralgia in a
      hierarchical manner, with calcium channel alpha2-delta ligands (gabapentin and
      pregabalin), tricyclic antidepressants (amitriptyline, nortriptyline, or
      desipramine), or topical lidocaine patches as first-line drugs. The safety and
      tolerability of pharmacologic therapies for pain are important issues to consider
      as postherpetic neuralgia affects primarily an older population. Patients should
      be educated on appropriate dosing, titration if applicable, the importance of
      adherence to treatment for optimal effectiveness, and possible side effects.
      Health-care professionals play a key role in helping to ameliorate the pain
      caused by postherpetic neuralgia through early recognition and diligent
      assessment of the problem; recommending evidence-based treatments; and monitoring
      treatment adherence, adverse events, responses, and expectations. Nurse
      practitioners are especially crucial in establishing communication with patients
      and encouraging the initiation of appropriate pain-relieving treatments.

PMID- 27703367
TI  - Efficacy and safety of daptomycin for skin and soft tissue infections: a
      systematic review with trial sequential analysis.
AB  - BACKGROUND: Skin and soft tissue infections (SSTIs) are significant indications
      for antibiotic treatment. Daptomycin, a novel antibiotic, has been registered and
      licensed to be used in the treatment of these infections. However, its efficacy
      and safety remain controversial. OBJECTIVE: The objective of this study was to
      conduct a systematic review with trial sequential analysis (TSA) to evaluate the
      efficacy and safety of daptomycin for the treatment of SSTIs and to analyze
      whether the available sample size has been large enough and is conclusive.
      METHODS: PubMed, the Cochrane Library, and EMBASE were searched for published
      randomized controlled trials (RCTs) that compared daptomycin with other
      antibiotics in adult patients with SSTIs up to February 2016. RESULTS: This meta
      analysis included eight randomized controlled trials (n=2,002). There was no
      difference in either the clinical success rate (intention-to-treat population:
      relative risk [RR] =1.04, 95% confidence interval [CI] =0.99-1.10, P=0.12;
      clinically evaluable population: RR =1.00, 95% CI =0.97-1.04, P=0.82) or the
      microbiological success rate (RR =1.00, 95% CI =0.95-1.06, P=0.92) between the
      daptomycin and comparator groups for treating SSTIs, which was confirmed by TSA.
      Compared with vancomycin, daptomycin exhibited no advantage in increasing the
      clinical success rate (RR =1.03, 95% CI =0.95-1.13, P=0.47), and this was also
      confirmed by TSA. All-cause mortality, overall treatment-related adverse events,
      and creatine phosphokinase events were similar between these two groups.
      CONCLUSION: Daptomycin and comparator drugs are equally efficacious with regard
      to clinical and microbiological success for patients with SSTIs, and TSA showed
      that no additional randomized controlled trials are required. Although daptomycin
      is a good alternative when other antibiotics are contraindicated for patients
      with SSTIs and it can serve as a first-line treatment for SSTIs, clinicians
      should be aware of potential adverse events, such as daptomycin-induced acute
      eosinophilic pneumonia and creatine phosphokinase, when treating patients with
      daptomycin.

PMID- 27703370
TI  - Expression of PER, CRY, and TIM genes for the pathological features of colorectal
      cancer patients [Retraction].
AB  - [This retracts the article on p. 1997 in vol. 9, PMID: 27103825.][This retracts
      the article on p. 841 in vol. 28.].

PMID- 27703369
TI  - Multidisciplinary rehabilitation for patients with cerebral palsy: improving long
      term care.
AB  - Cerebral palsy (CP) is one of the most frequent causes of child disability in
      developed countries. Children with CP need lifelong assistance and care. The
      current prevalence of CP in industrialized countries ranges from 1.5 to 2.5 per
      1,000 live births, with one new case every 500 live births. Children with CP have
      an almost normal life expectancy and mortality is very low. Despite the low
      mortality rate, 5%-10% of them die during childhood, especially when the severe
      motor disability is comorbid with epilepsy and severe intellectual disability.
      Given this life expectancy, children with CP present with a lifelong disability
      of varying severity and complexity, which requires individualized pathways of
      care. There are no specific treatments that can remediate the brain damage
      responsible for the complex clinical-functional dysfunctions typical of CP. There
      are, however, a number of interventions (eg, neurorehabilitation, functional
      orthopedic surgery, medication, etc) aimed at limiting the damage secondary to
      the brain insult and improving these patients' activity level and participation
      and, therefore, their quality of life. The extreme variability of clinical
      aspects and the complexity of affected functions determine a multifaceted skill
      development in children with CP. There is a need to provide them with long-term
      care, taking into account medical and social aspects as well as rehabilitation,
      education, and assistance. This long-term care must be suited according to
      children's developmental stage and their physical, psychological, and social
      development within their life contexts. This impacts heavily on the national
      health systems which must set up a network of services for children with CP, and
      it also impacts heavily on the family as a whole, due to the resulting distress,
      adjustment efforts, and changes in quality of life. This contribution is a
      narrative review of the current literature on long-term care for children with
      CP, aiming at suggesting reflections to improve these children's care.

PMID- 27703371
TI  - Identifying module biomarkers from gastric cancer by differential correlation
      network.
AB  - Gastric cancer (stomach cancer) is a severe disease caused by dysregulation of
      many functionally correlated genes or pathways instead of the mutation of
      individual genes. Systematic identification of gastric cancer biomarkers can
      provide insights into the mechanisms underlying this deadly disease and help in
      the development of new drugs. In this paper, we present a novel network-based
      approach to predict module biomarkers of gastric cancer that can effectively
      distinguish the disease from normal samples. Specifically, by assuming that
      gastric cancer has mainly resulted from dysfunction of biomolecular networks
      rather than individual genes in an organism, the genes in the module biomarkers
      are potentially related to gastric cancer. Finally, we identified a module
      biomarker with 27 genes, and by comparing the module biomarker with known gastric
      cancer biomarkers, we found that our module biomarker exhibited a greater ability
      to diagnose the samples with gastric cancer.

PMID- 27703372
TI  - Consolidation chemotherapy improves progression-free survival in stage III small
      cell lung cancer following concurrent chemoradiotherapy: a retrospective study.
AB  - BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for
      limited-stage small-cell lung cancer (LD-SCLC). However, the efficacy of
      consolidation chemotherapy (CCT) in LD-SCLC remains controversial despite several
      studies that were performed in the early years of CCT use. The aim of this study
      was to reevaluate the effectiveness and toxicities associated with CCT. METHODS:
      This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small
      cell lung cancer (SCLC) who underwent CCRT from January 2001 to December 2013 at
      Sun Yat-Sen University Cancer Center (SYSUCC). Overall survival (OS) and
      progression-free survival (PFS) were analyzed using Kaplan-Meier methods.
      Univariate and multivariate analyses were performed to analyze patient prognosis
      factors. RESULTS: Among the 177 patients, 72 (41%) received CCT and 105 (59%) did
      not receive CCT. PFS was significantly better for patients in the CCT group
      compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9
      months, respectively, P=0.031), whereas the differences in OS were not
      statistically significant (median OS: 31.6 vs 24.8 months, respectively,
      P=0.118). The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT
      group and 27.6% and 6.7% for patients in the non-CCT group, respectively.
      Multivariate analysis revealed that having a pretreatment carcinoembryonic
      antigen level <5 ng/mL (P=0.035), having undergone prophylactic cranial
      irradiation (P<0.001), and having received CCT (P=0.002) could serve as favorable
      independent prognostic factors for PFS. Multivariate analysis for OS also showed
      that having undergone PCI (P<0.001) and having received CCT (P=0.006) were
      independent significant prognostic factors. CONCLUSION: CCT can improve PFS for
      patients with stage IIIA and IIIB SCLC following CCRT without significantly
      increasing treatment-related toxicities.

PMID- 27703373
TI  - The expressions of NEDD9 and E-cadherin correlate with metastasis and poor
      prognosis in triple-negative breast cancer patients.
AB  - BACKGROUND: Neural precursor cell expressed, developmentally downregulated 9
      (NEDD9), a member of Crk-associated substrate family, is involved in cancer cell
      adhesion, migration, invasion, and epithelial-mesenchymal transition. E-cadherin
      is a key event in the cellular invasion during the epithelial-mesenchymal
      transition mechanism. The aim of this study was to evaluate the association among
      NEDD9 expression, E-cadherin expression, and survival in triple-negative breast
      cancer (TNBC) patients. METHODS: NEDD9 and E-cadherin expressions were analyzed
      by immunohistochemistry in 106 TNBC patients and 120 non-TNBC patients. And the
      association of clinicopathological factors with survival was analyzed using
      Kaplan-Meier analysis and Cox regression in TNBC patients. RESULTS: The results
      revealed that the rate of increased expression of NEDD9 and reduced expression of
      E-cadherin was significantly higher in TNBC group than that in non-TNBC group
      (P<0.001, both). Comparison of features between TNBC and non-TNBC groups showed
      that histological type (P=0.026) and lymph node metastasis (P=0.001) were
      significantly different. Correlation analysis showed that positive NEDD9
      expression and negative E-cadherin expression were significantly correlated with
      lymph node metastasis and tumor-node-metastasis stage (P<0.05). In addition, the
      enhanced NEDD9 expression was significantly associated with a reduced 5-year
      survival for TNBC patients (overall survival [OS]: P=0.013; disease-free survival
      [DFS]: P=0.021). Negative E-cadherin expression showed a significantly worse 5
      year OS and DFS (OS: P=0.011; DFS: P=0.012). Multivariate analysis showed that
      lymph node metastasis (OS: P=0.006; DFS: P=0.004), tumor-node-metastasis stage
      (OS: P=0.012; DFS: P=0.001), NEDD9 (OS: P=0.046; DFS: P=0.022), and E-cadherin
      (OS: P=0.022; DFS: P=0.025) independently predicted a poor prognosis of OS and
      DFS. Moreover, patients with NEDD9-positive/E-cadherin-negative expression had a
      significantly worse outcome than other groups (OS: P=0.004; DFS: P=0.001).
      CONCLUSION: Our finding demonstrated the potential value of NEDD9 and E-cadherin
      expression levels as prognostic molecular markers and a target for new therapies
      for TNBC patients.

PMID- 27703374
TI  - Pretreatment neutrophil-to-lymphocyte ratio as a survival predictor for small
      cell lung cancer.
AB  - BACKGROUND: The inflammatory response indexes, neutrophil-to-lymphocyte ratio
      (NLR) and platelet-to-lymphocyte ratio (PLR), have prognostic value for a variety
      of cancers. However, their prognostic value for small-cell lung cancer (SCLC) has
      been rarely reported. In this study, we monitored changes of NLR and PLR along
      with the clinical outcomes in patients with limited-stage and extensive-stage
      SCLC who received standard treatments. MATERIALS AND METHODS: We retrospectively
      reviewed the records of 153 patients who were pathologically diagnosed with SCLC
      and collected their hematological data at different time points during disease
      and treatment process. Kaplan-Meier analysis and Cox proportional hazards models
      were used to determine the prognostic significance of NLR and PLR for overall
      survival (OS) and progression-free survival (PFS). RESULTS: The median OS and PFS
      for all patients were 23.3 months and 11.0 months, respectively. After applying
      cutoffs of 3.2 for NLR and 122.7 for PLR, NLR, but not PLR, showed independent
      prognostic significance. High-NLR group was associated with shorter median OS
      (high vs low, 18.0 months vs 31.0 months, P<0.01) and shorter PFS (high vs low,
      9.3 months vs 13.0 months, P=0.006). The cumulative 3-year OS rate and 3-year PFS
      rate of high-NLR group versus low-NLR group were 14.3% versus 37.3% and 8.6%
      versus 22.9%, respectively. In the multivariate analysis, both disease stage and
      NLR at diagnosis were independent prognostic factors for OS and PFS. CONCLUSION:
      The NLR at diagnosis showed significant prognostic value for clinical outcomes in
      SCLC patients treated with chemoradiotherapy. As an effective biomarker of host
      immune status, NLR could potentially help monitoring disease progression and
      adjusting treatment plans.

PMID- 27703376
TI  - A case report and literature review of primary resistant Hodgkin lymphoma: a
      response to anti-PD-1 after failure of autologous stem cell transplantation and
      brentuximab vedotin.
AB  - Hodgkin lymphoma (HL) is a highly curable hematologic malignancy, and ~70% of
      cases can be cured with combination chemotherapy with or without radiation.
      However, patients with primary resistant disease have a cure rate of <30%. For
      such patients, high-dose chemotherapy followed by autologous stem cell
      transplantation (ASCT) is considered to be the standard treatment. If patients
      fail to respond to ASCT or relapse soon thereafter, they usually receive another
      ASCT, allogeneic stem cell transplantation or treatment with novel agents. This
      case report presents the case of a 54-year-old patient with primary resistant HL
      who received single-agent treatment, brentuximab vedotin, after ASCT relapse.
      Despite treatment with brentuximab vedotin, the disease continued to progress. In
      patients with such highly resistant disease, the treatment options are limited.
      Depending on the physical condition and the willingness of the patient,
      pembrolizumab, a programmed cell death protein-1 inhibitor, can be given as
      salvage therapy. But, out of our expectation, the patient achieved a very good
      partial response after four cycles of pembrolizumab. No serious adverse events
      were observed with pembrolizumab treatment. This case provides support for a new
      and effective strategy for treating primary resistant Hodgkin lymphoma.

PMID- 27703375
TI  - Prognostic value of decreased microRNA-133a in solid cancers: a meta-analysis.
AB  - OBJECTIVE: Increasing evidence indicates that the decreased expression of
      microRNA-133a (miR-133a) may be correlated with poor survival for cancer
      patients. Thus, we performed this meta-analysis to evaluate the prognostic value
      of decreased miR-133a in solid cancers. METHODS: Eligible studies were gathered
      by searching on PubMed, Web of Science, and Embase. Using the STATA 12.0
      software, the pooled hazard ratios (HRs) and their corresponding 95% confidence
      intervals (CIs) for total and subgroup analyses were calculated to investigate
      the possible correlation between decreased miR-133a and overall survival (OS) of
      patients with cancer. RESULTS: Ten studies were enrolled in this meta-analysis.
      The pooled result showed that decreased expression of miR-133a predicted poor OS
      in solid cancer patients (HR =1.62, 95% CI: 1.16-2.24, P=0.004). Compared with
      the total pooled HR, further analyses indicated that the subgroups of digestive
      system neoplasms (HR =1.73, 95% CI: 1.20-2.51, P=0.003), frozen tissue
      preservation (HR =1.89, 95% CI: 1.41-2.53, P<0.001), and multivariate analysis
      (HR =2.07, 95% CI: 1.42-3.02, P<0.001) exhibited stronger connection between
      decreased miR-133a expression and OS outcome. CONCLUSION: This meta-analysis
      suggested that decreased miR-133a was associated with poor OS in patients with
      solid cancer. Because of the data in our study are limited, additional studies
      are required to verify the poor prognosis of decreased miR-133a in solid tumors.

PMID- 27703377
TI  - Apparent diffusion coefficient values detected by diffusion-weighted imaging in
      the prognosis of patients with locally advanced esophageal squamous cell
      carcinoma receiving chemoradiation.
AB  - PURPOSE: Previous studies have demonstrated that apparent diffusion coefficient
      (ADC) values measured by magnetic resonance imaging have prognostic value in
      patients with esophageal squamous cell carcinoma (ESCC). However, the role of ADC
      needs to be validated in a cohort of Chinese ESCC patients. This study assessed
      the role of ADC in predicting the outcome of patients with ESCC treated only by
      chemoradiation in the People's Republic of China. PATIENTS AND METHODS: Seventy
      three patients with local advanced ESCC were retrospectively analyzed in this
      study; none of the patients underwent surgery before or after chemoradiation. The
      ADC values of the primary tumors were determined by magnetic resonance imaging.
      The ADC values were then correlated with clinicopathological and other
      radiological parameters. Survival analysis was carried out to determine if ADC
      had an impact on survival of these patients. RESULTS: The median ADC value of the
      esophageal cancer tissue was 1.256*10-3 mm2/sec (range: 0.657-2.354*10-3 mm2/sec,
      interquartile range 0.606*10-3 mm2/sec). No clinicopathological or radiological
      parameters were associated with the ADC values except the sites of tumor tissues.
      ADC <1.076*10-3 mm2/sec predicted significantly worse survival in patients with
      ESCC (12.9 months vs undefined, P=0.0108). CONCLUSION: The ADC value is a potent
      prognostic factor which can be used to predict the outcome of patients with ESCC
      treated only by chemoradiation.

PMID- 27703378
TI  - A clear cell adenocarcinoma of the gallbladder with hepatoid differentiation:
      case report and review of literature.
AB  - An 80-year-old male was referred to our department for a gallbladder mass. He
      denied any history of alcohol consumption or cholecystitis and smoking. Hepatitis
      B surface antigen test and antihepatitis C antibody test were found to be
      negative. Serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen
      were elevated (CA19-9 was 59.92 U/mL and carcinoembryonic antigen was 12.64
      ng/mL), whereas alpha-fetoprotein was below the normal limit (2.46 ng/mL).
      Computed tomography scan revealed a solid mass with measurements of 4.6*5.6*7.1
      cm, which nearly filled the whole gallbladder space. Radical cholecystectomy,
      including segments IV B and V of the liver and lymphadenectomy, was performed.
      The neoplasm in gallbladder was completely resected, and the patient obtained a
      negative margin. Histological and immunohistochemical profile suggested a clear
      cell adenocarcinoma of the gallbladder with hepatoid differentiation. After
      reviewing the literature, we reported that this case is the first identified case
      of cell adenocarcinoma of the gallbladder with extensive hepatoid
      differentiation. However, clinical features of clear cell adenocarcinoma with
      hepatoid differentiation remain unclear due to the extremely rare incidence.
      There was no indication of adjuvant chemotherapy and no literature has been
      reported on the application of chemotherapy. This case showed a promising
      clinical outcome after curative resection, which indicated that surgical
      treatment could be potentially considered for suitable patients.

PMID- 27703379
TI  - Anatomic distribution of supraclavicular lymph node in patients with esophageal
      cancer.
AB  - PURPOSE: Definitive chemoradiation therapy remains the standard of care for
      patients with localized esophageal carcinoma who choose nonsurgical management.
      However, there is no consensus regarding delineation of the nodal clinical target
      volume (CTVn), especially for lower cervical lymph nodes. This study aimed to map
      the location of metastatic supraclavicular lymph nodes in thoracic esophageal
      carcinoma patients with supraclavicular node involvement and generate an atlas to
      delineate the CTVn for elective nodal radiation of esophageal squamous cell
      carcinoma. PATIENTS AND METHODS: In this study, the supraclavicular regional
      lymph node was further divided into four subgroups. The locations of the involved
      supraclavicular nodes for all patients were then transferred onto a template
      computed tomography (CT) image. A volume probability map was then generated with
      nodal volumes, and was displayed on the template CT to provide a visual
      impression of nodal frequencies and anatomic distribution. RESULTS: We identified
      154 supraclavicular nodal metastases based on CT image in 96 patients. Of these,
      29.2% were located in group I region, 59.7% in group II region, 10.4% in group
      III region, and 0.7% in group IV region. CONCLUSION: On the basis of our study,
      we suggest that the appropriate radiation field of CTVn should include the group
      I and II regions and the CTVn exterior margin along the lateral side of the
      internal jugular vein may be suitable.

PMID- 27703380
TI  - Evaluation of c-Met, HGF, and HER-2 expressions in gastric carcinoma and their
      association with other clinicopathological factors.
AB  - BACKGROUND: Met and HER-2 are proto-oncogenes encoding receptor tyrosine kinase c
      Met and HER-2, respectively. Hepatocyte growth factor (HGF) is a ligand of c-Met.
      The frequency of c-Met, HGF, and HER-2 expressions in gastric cancer and their
      association with other clinicopathological factors have not been fully
      understood. PATIENTS AND METHODS: Patients with stage 1-4 disease were analyzed.
      Expressions of c-Met, HGF, and HER-2 were examined using immunohistochemistry.
      RESULTS: A total of 143 patients, 97 males and 46 females, were included. C-Met
      scores were 3(+) in 31.5%, 2(+) in 27.3%, and 1(+) in 10.5% of the patients.
      There was no statistically significant difference in age, sex, tumor location,
      differentiation, Lauren classification, TNM staging, presence of distant
      metastasis, depth of tumor invasion (T), lymphovascular invasion, and survival
      between c-Met subgroups. Overall HGF positivity was 20.6%. HER-2 scores were 3(+)
      in 9.1%, 2(+) in 9.8%, and 1(+) in 16.1% of the patients. HER-2 overexpression
      was associated with better differentiation, intestinal subtype, and advanced
      stage. C-Met overexpressions were 84.6% in the HER-2-overexpression-positive
      group and 56.2% in the HER-2-overexpression-negative group. There were no
      statistically significant differences in survival between the high c-Met
      expression-positive and -negative stage 3 and stage 4 patients and between the
      HGF-positive and -negative groups. The mean survival was 11.6+/-6.3 months in the
      HER-2-overexpression-positive stage 4 group and 11.9+/-6.8 months in the HER-2
      overexpression-negative stage 4 group. There were no statistically significant
      differences in survival between the two groups. CONCLUSION: c-Met was not
      associated with any prognostic factors in gastric cancer. HER-2 was associated
      with better differentiation, intestinal subtype, advanced stage, and c-Met
      overexpression.

PMID- 27703381
TI  - An evaluation of the diagnostic efficacy of fine needle aspiration biopsy in
      patients operated for a thyroid nodular goiter.
AB  - BACKGROUND: Thyroid cancer (TC) comprises 1% of all carcinomas and is the most
      common malignancy of the endocrine system. The disease is more common in women,
      with its peak morbidity observed in 40-50-year-old patients. The main risk
      factors include radiation, iodine deficiency, hereditary background, and genetic
      mutations. Among all diagnosed thyroid nodules, 5%-30% will evolve into cancer.
      The gold-standard procedure in the preoperative evaluation of a nodular goiter,
      apart from ultrasonography, is fine needle aspiration (FNA) biopsy. The FNA
      biopsy is favored for its simplicity, safety, and high specificity and
      sensitivity rates. AIM: The aim of our study was to evaluate the clinical
      efficacy of FNA based on the patients' register. MATERIALS AND METHODS: In the
      Department of Surgery at the 4th Military Teaching Hospital in Wroclaw, 2,133
      patients underwent thyroid surgery for thyroid goiter between 1996 and 2015. One
      hundred and eight cases of TC were diagnosed and of these, 66 patients had a
      preoperative FNA. RESULTS: Fourteen FNA biopsies (21%) revealed cancer, all of
      which were confirmed in the postoperative histopathology, although six cases of
      FNA-diagnosed cancer revealed a different histological type postoperatively.
      Eighteen FNA biopsies (27%) were suspected of being malignant. A disturbingly
      high rate of "benign" FNA biopsies (32 cases; 48%) revealed TC after surgery.
      CONCLUSION: It is of great importance that the quality and quantity of FNA
      biopsies that are performed have been improved, especially due to the wide
      adoption of the Bethesda cytological evaluation system. FNA biopsy remains an
      obligatory and valuable diagnostic tool in thyroid nodules, but it is still
      insufficient as a standard procedure. A preoperative biopsy should always be
      related to all the available clinical data in order to provide the best treatment
      option for each patient individually.

PMID- 27703384
TI  - Economic evaluation of obinutuzumab in combination with chlorambucil in first
      line treatment of patients with chronic lymphocytic leukemia in Spain.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of obinutuzumab in combination with
      chlorambucil (GClb) versus rituximab plus chlorambucil (RClb) in the treatment of
      adults with previously untreated chronic lymphocytic leukemia (CLL) and with
      comorbidities that make them unsuitable for full-dose fludarabine-based therapy,
      from the perspective of the Spanish National Health System. METHODS: A Markov
      model was developed with three mutually exclusive health states: progression-free
      survival (with or without treatment), progression, and death. Survival time for
      the two treatments was modeled based on the results of CLL11 clinical trial and
      external sources. Each health state was associated with a utility value and
      direct medical costs. The utilities were obtained from a utility elicitation
      study conducted in the UK. Costs and general background mortality data were
      obtained from published Spanish sources. Deterministic and probabilistic analyses
      were conducted, with a time frame of 20 years. The health outcomes were measured
      as life years (LYs) gained and quality-adjusted life years (QALYs) gained.
      Efficiency was measured as the cost per LY or per QALY gained of the most
      effective regimen. RESULTS: In the deterministic base case analysis, each patient
      treated with GClb resulted in 0.717 LYs gained and 0.673 QALYs gained versus
      RClb. The cost per LY and per QALY gained with GClb versus RClb was ?23,314 and
      ?24,838, respectively. The results proved stable in most of the univariate and
      probabilistic sensitivity analyses, with a probabilistic cost per QALY gained of
      ?24,734 (95% confidence interval: ?21,860-28,367). CONCLUSION: Using GClb to
      treat patients with previously untreated CLL for whom full-dose fludarabine-based
      therapy is unsuitable allows significant gains in terms of LYs and QALYs versus
      treatment with RClb. Treatment with GClb versus RClb can be regarded as efficient
      when considered the willingness to pay thresholds commonly used in Spain.

PMID- 27703383
TI  - Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole
      therapy.
AB  - Aspergillus fumigatus is the main fungus cultured in the airways of patients with
      cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of
      CF patients and is clearly associated with airway damage and lung function
      decline. The effects of A. fumigatus colonization in the absence of allergic
      bronchopulmonary aspergillosis are less well established. Retrospective clinical
      studies found associations of A. fumigatus-positive cultures with computed
      tomography scan abnormalities, greater risk of CF exacerbations and
      hospitalizations, and/or lung function decline. These findings were somewhat
      variable among studies and provided only circumstantial evidence for a role of A.
      fumigatus colonization in CF lung disease progression. The availability of a
      growing number of oral antifungal triazole drugs, together with the results of
      nonrandomized case series suggesting positive effects of azole therapies, makes
      it tempting to treat CF patients with these antifungal drugs. However, the only
      randomized controlled trial that has used itraconazole in CF patients showed no
      significant benefit. Because triazoles may have significant adverse effects and
      drug interactions, and because their prolonged use has been associated with the
      emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or
      not CF patients benefit from azole therapy.

PMID- 27703382
TI  - Chronic hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease
      resulting from inhalation of a large variety of antigens by susceptible
      individuals. The disease is best classified as acute and chronic. Chronic HSP can
      be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a
      worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic
      criteria are proposed for both chronic forms based on exposure, lung
      auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and
      biopsies. Treatment options are limited, but lung transplantation results in
      greater survival in comparison to idiopathic pulmonary fibrosis. Randomized
      trials with new antifibrotic agents are necessary.

PMID- 27703385
TI  - Patient-level costs of major cardiovascular conditions: a review of the
      international literature.
AB  - OBJECTIVE: Robust cost estimates of cardiovascular (CV) events are required for
      assessing health care interventions aimed at reducing the economic burden of
      major adverse CV events. This review synthesizes international cost estimates of
      CV events. METHODS: MEDLINE database was searched electronically for English
      language studies published during 2007-2012, with cost estimates for CV events of
      interest - unstable angina, myocardial infarction, heart failure, stroke, and CV
      revascularization. Included studies provided at least one estimate of patient
      level direct costs in adults for any identified country. Information on study
      characteristics and cost estimates were collected. All costs were adjusted for
      inflation to 2013 values. RESULTS: Across the 114 studies included, the average
      cost was US $6,466 for unstable angina, $11,664 for acute myocardial infarction,
      $11,686 for acute heart failure, $11,635 for acute ischemic stroke, $37,611 for
      coronary artery bypass graft, and $13,501 for percutaneous coronary intervention.
      The ranges for cost estimates varied widely across countries with US cost
      estimate being at least twice as high as European Union costs for some
      conditions. Few studies were found on populations outside the US and European
      Union. CONCLUSION: This review showed wide variation in the cost of CV events
      within and across countries, while showcasing the continuing economic burden of
      CV disease. The variability in costs was primarily attributable to differences in
      study population, costing methodologies, and reporting differences. Reliable cost
      estimates for assessing economic value of interventions in CV disease are needed.

PMID- 27703386
TI  - A hospital cost analysis of a fibrin sealant patch in soft tissue and hepatic
      surgical bleeding.
AB  - BACKGROUND: Despite hemostat use, uncontrolled surgical bleeding is prevalent.
      Drawbacks of current hemostats include limitations with efficacy on first attempt
      and suboptimal ease-of-use. Evarrest(r) is a novel fibrin sealant patch that has
      demonstrated high hemostatic efficacy compared with standard of care across
      bleeding severities. The objective of this study was to conduct a hospital cost
      analysis of the fibrin sealant patch versus standard of care in soft tissue and
      hepatic surgical bleeding. METHODS: The analysis quantified the 30-day costs of
      each comparator from a hospital perspective. Published US unit costs were applied
      to resource use (ie, initial treatment, retreatment, operating time,
      hospitalization, transfusion, and ventilator) reported in four trials. A
      "surgical" analysis included resources clinically related to the hemostatic
      benefit of the fibrin sealant patch, whereas a "hospital" analysis included all
      resources reported in the trials. An exploratory subgroup analysis focused solely
      on coagulopathic patients defined by abnormal blood test results. RESULTS: The
      surgical analysis predicted cost savings of $54 per patient with the fibrin
      sealant patch compared with standard of care (net cost impact: -$54 per patient;
      sensitivity range: -$1,320 to $1,213). The hospital analysis predicted further
      cost savings with the fibrin sealant patch (net cost impact of -$2,846 per
      patient; sensitivity range: -$1,483 to -$5,575). Subgroup analyses suggest that
      the fibrin sealant patch may provide dramatic cost savings in the coagulopathic
      subgroup of $3,233 (surgical) and $9,287 (hospital) per patient. Results were
      most sensitive to operating time and product units. CONCLUSION: In soft tissue
      and hepatic problematic surgical bleeding, the fibrin sealant patch may result in
      important hospital cost savings.

PMID- 27703387
TI  - Cost-effectiveness of dipeptidyl peptidase-4 inhibitor monotherapy in elderly
      type 2 diabetes patients in Thailand.
AB  - BACKGROUND: The management of type 2 diabetes mellitus (T2DM) in elderly
      population poses many challenges. Dipeptidyl peptidase-4 (DPP-4) inhibitors show
      particular promise due to excellent tolerability profiles, low risk of
      hypoglycemia, and little effect on body weight. This study evaluated, from the
      health care system's perspective, the long-term cost-effectiveness of DPP-4
      inhibitor monotherapy vs metformin and sulfonylurea (SFU) monotherapy in Thai
      elderly T2DM patients. METHODS: The clinical efficacy was estimated from a
      systematic review and meta-analysis. Baseline cohort characteristics and cost
      parameters were obtained from published studies and hospital databases in
      Thailand. A validated IMS CORE Diabetes Model version 8.5 was used to project
      clinical and economic outcomes over a lifetime horizon using a 3% annual discount
      rate. Costs were expressed in 2014 Thai Baht (THB) (US dollar value). Incremental
      cost-effectiveness ratios were calculated. Base-case assumptions were assessed
      through several sensitivity analyses. RESULTS: For treating elderly T2DM
      patients, DPP-4 inhibitors were more expensive and less effective, ie, a
      dominated strategy, than the metformin monotherapy. Compared with SFU, treatment
      with DPP-4 inhibitors gained 0.031 more quality-adjusted life years (QALYs) at a
      total cost incurred over THB113,701 or US$3,449.67, resulting in an incremental
      cost-effectiveness ratio of THB3.63 million or US$110,133.50 per QALY. At the
      acceptable Thai ceiling threshold of THB160,000/QALY (US$4,854.37/QALY), DPP-4
      inhibitors were not a cost-effective treatment. CONCLUSION: DPP-4 inhibitor
      monotherapy is not a cost-effective treatment for elderly T2DM patients compared
      with metformin monotherapy and SFU monotherapy, given current resource
      constraints in Thailand.

PMID- 27703388
TI  - Cost-effectiveness analysis of online hemodiafiltration versus high-flux
      hemodialysis.
AB  - BACKGROUND: Clinical studies suggest that hemodiafiltration (HDF) may lead to
      better clinical outcomes than high-flux hemodialysis (HF-HD), but concerns have
      been raised about the cost-effectiveness of HDF versus HF-HD. Aim of this study
      was to investigate whether clinical benefits, in terms of longer survival and
      better health-related quality of life, are worth the possibly higher costs of HDF
      compared to HF-HD. METHODS: The analysis comprised a simulation based on the
      combined results of previous published studies, with the following steps: 1)
      estimation of the survival function of HF-HD patients from a clinical trial and
      of HDF patients using the risk reduction estimated in a meta-analysis; 2)
      simulation of the survival of the same sample of patients as if allocated to HF
      HD or HDF using three-state Markov models; and 3) application of state-specific
      health-related quality of life coefficients and differential costs derived from
      the literature. Several Monte Carlo simulations were performed, including
      simulations for patients with different risk profiles, for example, by age
      (patients aged 40, 50, and 60 years), sex, and diabetic status. Scatter plots of
      simulations in the cost-effectiveness plane were produced, incremental cost
      effectiveness ratios were estimated, and cost-effectiveness acceptability curves
      were computed. RESULTS: An incremental cost-effectiveness ratio of ?6,982/quality
      adjusted life years (QALY) was estimated for the baseline cohort of 50-year-old
      male patients. Given the commonly accepted threshold of ?40,000/QALY, HDF is cost
      effective. The probabilistic sensitivity analysis showed that HDF is cost
      effective with a probability of ~81% at a threshold of ?40,000/QALY. It is
      fundamental to measure the outcome also in terms of quality of life. HDF is more
      cost-effective for younger patients. CONCLUSION: HDF can be considered cost
      effective compared to HF-HD.

PMID- 27703390
TI  - Splenosis involving the gastric fundus, a rare cause of massive upper
      gastrointestinal bleeding: a case report and review of the literature.
AB  - Splenosis, the autotransplantation of splenic tissue following splenic trauma, is
      uncommonly clinically significant. Splenosis is typically diagnosed incidentally
      on imaging or at laparotomy and has been mistakenly attributed to various
      malignancies and pathological conditions. On the rare occasion when splenosis
      plays a causative role in a pathological condition, a diagnostic challenge may
      ensue that can lead to a delay in both diagnosis and treatment. The following
      case report describes a patient presenting with a massive upper gastrointestinal
      bleed resulting from arterial enlargement within the gastric fundus secondary to
      perigastric splenosis. The cause of the bleeding was initially elusive and this
      case highlights the importance of a thorough clinical history when faced with a
      diagnostic challenge. Treatment options, including the successful use of
      transarterial embolization in this case, are also presented.

PMID- 27703389
TI  - Ineffective esophageal motility and the vagus: current challenges and future
      prospects.
AB  - Ineffective esophageal motility (IEM) is characterized by low to very low
      amplitude propulsive contractions in the distal esophagus, hence primarily
      affecting the smooth muscle part of the esophagus. IEM is often found in patients
      with dysphagia or heartburn and is commonly associated with gastroesophageal
      reflux disease. IEM is assumed to be associated with ineffective bolus transport;
      however, this can be verified using impedance measurements or evaluation of a
      barium coated marshmallow swallow. Furthermore, water swallows may not assess
      accurately the motor capabilities of the esophagus, since contraction amplitude
      is strongly determined by the size and consistency of the bolus. The "peristaltic
      reserve" of the esophagus can be evaluated by multiple rapid swallows that, after
      a period of diglutative inhibition, normally give a powerful peristaltic
      contraction suggestive of the integrity of neural orchestration and smooth muscle
      action. The amplitude of contraction is determined by a balance between intrinsic
      excitatory cholinergic, inhibitory nitrergic, as well as postinhibition rebound
      excitatory output to the musculature. This is strongly influenced by vagal
      efferent motor neurons and this in turn is influenced by vagal afferent neurons
      that send bolus information to the solitary nucleus where programmed activation
      of the vagal motor neurons to the smooth muscle esophagus is initiated. Solitary
      nucleus activity is influenced by sensory activity from a large number of organs
      and various areas of the brain, including the hypothalamus and the cerebral
      cortex. This allows interaction between swallowing activities and respiratory and
      cardiac activities and allows the influence of acute and chronic emotional states
      on swallowing behavior. Interstitial cells of Cajal are part of the sensory units
      of vagal afferents, the intramuscular arrays, and they provide pacemaker activity
      to the musculature that can generate peristalsis in the absence of innervation.
      This indicates that a low-amplitude esophageal contraction, observed as IEM, can
      be caused by a multitude of factors, and therefore many pathways can be
      potentially explored to restore normal esophageal peristalsis.

PMID- 27703391
TI  - Cigarette smoking adversely affects disease activity and disease-specific quality
      of life in patients with Crohn's disease at a tertiary referral center.
AB  - PURPOSE: Smoking has a negative impact on disease activity in Crohn's disease
      (CD). Smoking may also affect the quality of life, but this has not been
      evaluated using validated measures over time. We assessed the relationship
      between smoking and disease-specific quality of life over time in a tertiary
      referral inflammatory bowel disease cohort. PATIENTS AND METHODS: Retrospective
      cohort study from July 2004 to July 2009 in patients with CD identified from the
      University of Maryland, Baltimore, Institutional Review Board-approved University
      of Maryland School of Medicine Inflammatory Bowel Disease Program database.
      Smoking status was classified as current, former, and never. Age was categorized
      as <40 years, 40-59 years, and >=60 years. Index visit disease activity and
      quality of life was measured with the Harvey-Bradshaw index, and the Short
      Inflammatory Bowel Disease Questionnaire (SIBDQ). Repeated measures linear
      regression was used to assess the association between smoking and quality of life
      over time after adjustment for confounding variables. RESULTS: A total of 608
      patients were included, of whom 42% were male; 80% were Caucasian; 22% were
      current smokers; 24% were former smokers; and 54% were never smokers. Over time,
      adjusted Harvey-Bradshaw index scores declined in all patients, but current
      smokers had consistently higher scores. After adjustment for sex, age, and
      disease duration, never smokers had higher mean SIBDQ scores at index visit
      compared to former and current smokers (P<0.0001); all increased over time but
      SIBDQ scores for never smokers remained consistently highest. CONCLUSION: Smoking
      has a negative impact on disease activity and quality of life in patients with
      CD. Prospects of improved disease activity and quality of life should be proposed
      as an additional incentive to encourage smoking cessation in patients with CD.

PMID- 27703393
TI  - Effectiveness of low-dose intravenous ketamine to attenuate stress response in
      patients undergoing emergency cesarean section with spinal anesthesia.
AB  - PURPOSE: Cesarean section is a surgical procedure. Surgical procedures will
      induce stress responses, which may have negative impact on postoperative
      recovery. Ketamine plays a role in the homeostatic regulation of inflammatory
      response in order to attenuate stress response. We tried to determine the
      effectiveness of low-dose intravenous ketamine to attenuate stress response in
      patients undergoing emergency cesarean section with spinal anesthesia. PATIENTS
      AND METHODS: Thirty-six pregnant women undergoing emergency cesarean section with
      spinal anesthesia were randomly divided into two groups (n=18). Ketamine 0.3
      mg/kg (KET group) or NaCl 0.9% (NS group) was administered intravenously before
      the administration of spinal anesthesia. C-reactive protein (CRP) and neutrophil
      levels were measured preoperatively and postoperatively. RESULTS: Elevation of
      CRP stress response was lower in the KET group and significantly different
      (P<=0.05) from that in the NS group. Neutrophil level was elevated in both the
      groups and hence not significantly different from each other (P>0.05).
      Postoperative visual analog scale pain score was not significantly different
      between the two groups (P>0.05), but there was a statistically significant
      (P<=0.05) positive and weak correlation between visual analog scale and CRP level
      postoperatively. CONCLUSION: Low-dose intravenous ketamine effectively attenuates
      the CRP stress response in patients undergoing emergency cesarean section with
      spinal anesthesia.

PMID- 27703392
TI  - The treatment of nonunions with application of BMP-7 increases the expression
      pattern for angiogenic and inflammable cytokines: a matched pair analysis.
AB  - The local application of bone morphogenetic protein-7 (BMP-7) in combination with
      the transplantation of autologous bone graft improves the outcome in nonunion
      treatment; however, the specific reasons remain unclear. In this study, we sought
      to determine if the local application of BMP-7 contributes to improved bone
      regeneration in nonunion therapy by modulation of the angiogenic and inflammable
      cytokine expression patterns of the early inflammation response. Therefore, we
      utilized the analysis of serological cytokine expression patterns. As a matched
      pair analysis, best-fitting patients who were treated with transplantation of
      autologous bone graft (G1, n=10) were compared with patients who were treated
      with additional application of BMP-7 (G2, n=10). The changes in the cytokine
      expression patterns were monitored and correlated to clinical data of bone
      healing. Significant differences in angiogenesis potential (vascular endothelial
      growth factor [VEGF] serum levels) could be found in the first days after surgery
      (P<0.05). Furthermore, the increase and absolute amount of VEGF levels in the BMP
      7 group were considerably higher than in the control group during the first 2
      weeks after surgery. The expression pattern of inflammable cytokines showed
      noticeable differences in the time point of significant elevated levels, in
      particular, inflammable cytokines showed an earlier peak in G2. Furthermore,
      interleukin-6 was significantly elevated within the first week only, comparing G2
      to G1 (P<0.05). Our findings indicate that BMP-7 induces an early and more
      intense expression of VEGF via a direct and postulated indirect pathway, thereby
      providing a favorable environment for bone healing. Moreover, application of BMP
      7 leads to an earlier expression of known proinflammatory cytokines. The results
      of this study show that application of BMP-7 leads to costimulatory effect on
      both angiogenic and inflammable cytokine expression patterns that may serve as a
      possible stimulus for bone regeneration.

PMID- 27703394
TI  - Survey of pain specialists regarding conversion of high-dose intravenous to
      neuraxial opioids.
AB  - The conversion of high-dose intravenous (IV) opioids to an equianalgesic epidural
      (EP) or intrathecal (IT) dose is a common clinical dilemma for which there is
      little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1
      IT conversion ratio is commonly cited in the literature, especially for morphine.
      In this study, the authors surveyed 724 pain specialists to elucidate the ratios
      that respondents apply to convert high-dose IV morphine, hydromorphone, and
      fentanyl to both EP and IT routes. Eighty-three respondents completed the survey.
      Conversion ratios were calculated and entered into graphical scatter plots. The
      data suggest that there is wide variation in how pain specialists convert high
      dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most
      common answer of survey respondent, especially for morphine, though also for
      hydromorphone and fentanyl. Furthermore, more respondents applied a more
      aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting
      less spinal selectivity of those opioids compared with morphine. The authors
      conclude that there is little consensus on this issue and suggest that in the
      absence of better data, a conservative approach to opioid conversion between IV
      and neuraxial routes is warranted.

PMID- 27703395
TI  - Using social media to challenge unwarranted clinical variation in the treatment
      of chronic noncancer pain: the "Brainman" story.
AB  - There is a substantial clinical variation in the contemporary treatment of
      chronic noncancer pain reflecting different explanatory models and treatment
      emphasis. Hunter Integrated Pain Service and collaborators developed three key
      messaging videos outlining the foundations of chronic pain treatment, thus
      challenging unwarranted clinical variation and calling for greater therapeutic
      consistency. The videos were released on YouTube as a low-cost public health
      intervention. Each video used an evidenced informed script appropriate for low
      literacy and a cartoonist to provide matching images. The whole-person approach
      emphasized the role of the nervous system and active self-management approaches
      over passively received medical treatments. The first video was launched on
      YouTube in August 2011 and made freely available through a Creative Commons
      license. Multisource feedback led to refinement of key messages using a broader
      advisory group. Two further videos were launched on a dedicated YouTube channel
      in October 2014 and circulated through varied professional and consumer networks.
      All videos were widely viewed on YouTube, utilized by diverse health care
      organizations, and independently translated into multiple languages. They were
      embedded in multiple health-related websites. The first video "Understanding pain
      in less than 5 minutes" is known to have been translated into 15 languages by
      other health care organizations. The subsequent two videos (Brainman stops his
      opioids, and Brainman chooses) were translated into German and subtitled in
      French and Japanese. When the organization hosting the first video ceased
      operation in 2015 due to changes in primary health care funding, the video had
      received >700,000 views. Each of the three videos continues to receive ~1,500
      views per month on YouTube. Release of evidence-informed key messages via YouTube
      is a simple method of challenging clinical variation and providing education
      about chronic pain across the health care system and community.

PMID- 27703396
TI  - Epilepsy during pregnancy: focus on management strategies.
AB  - In the US, more than one million women with epilepsy are of childbearing age and
      have over 20,000 babies each year. Patients with epilepsy who become pregnant are
      at risk of complications, including changes in seizure frequency, maternal
      morbidity and mortality, and congenital anomalies due to antiepileptic drug
      exposure. Appropriate management of epilepsy during pregnancy may involve
      frequent monitoring of antiepileptic drug serum concentrations, potential
      preconception switching of antiepileptic medications, making dose adjustments,
      minimizing peak drug concentration with more frequent dosing, and avoiding
      potentially teratogenic medications. Ideally, preconception planning will be done
      to minimize risks to both the mother and fetus during pregnancy. It is important
      to recognize benefits and risks of current and emerging therapies, especially
      with revised pregnancy labeling in prescription drug product information. This
      review will outline risks for epilepsy during pregnancy, review various
      recommendations from leading organizations, and provide an evidence-based
      approach for managing patients with epilepsy before, during, and after pregnancy.

PMID- 27703397
TI  - Hyperglycemia in pregnancy: prevalence, impact, and management challenges.
AB  - Gestational diabetes mellitus (GDM) is one of the most common medical conditions
      in pregnancy, and the prevalence is growing with increasing rates of women of
      advanced age becoming pregnant and the increasing prevalence of maternal obesity
      and inactivity. GDM is associated with an increased risk of maternal and infant
      short- and long-term ill-health. There is a positive linear association between
      increasing maternal glucose at oral glucose tolerance testing and risk of
      important perinatal outcomes, including cesarean section, large for gestational
      age, and infant adiposity. A "step-up" approach, where diet and lifestyle
      information is provided followed by pharmacological interventions as required to
      control and reduce hyperglycemia, is effective at reducing the risk of
      macrosomia, but treatment of GDM will increase demand on health services. There
      is limited evidence to suggest which identification strategy is best or what
      thresholds should be used to diagnose GDM or what the effects of different
      diagnostic strategies have on short- or long-term maternal and offspring
      outcomes. Trials of interventions in pregnancy aimed at preventing GDM have not
      demonstrated a benefit; therefore, trials are needed to evaluate interventions
      aimed at optimizing the health of all women of childbearing age, outside of
      pregnancy. A consistent, evidence-based, sustained approach to supporting women
      to live healthily, including the achievement of a normal body mass index before
      and after pregnancy, is urgently needed.

PMID- 27703399
TI  - Acute chest pain after bench press exercise in a healthy young adult.
AB  - Bench press exercise, which involves repetitive lifting of weights to full arm
      extension while lying supine on a narrow bench, has been associated with
      complications ranging in acuity from simple pectoral muscle strain, to aortic and
      coronary artery dissection. A 39-year-old man, physically fit and previously
      asymptomatic, presented with acute chest pain following bench press exercise.
      Diagnostic evaluation led to the discovery of critical multivessel coronary
      occlusive disease, and subsequently, highly elevated levels of lipoprotein (a).
      Judicious use of ancillary testing may identify the presence of "high-risk"
      conditions in a seemingly "low-risk" patient. Emergency department evaluation of
      the young adult with acute chest pain must take into consideration an extended
      spectrum of potential etiologies, so as to best guide appropriate management.

PMID- 27703400
TI  - Body surface area: a predictor of response to red blood cell transfusion.
AB  - A current focus of transfusion medicine is a judicious strategy in transfusion of
      blood products. Unfortunately, our ability to predict hemoglobin (Hgb) response
      to transfusion has been limited. The objective of this study was to determine
      variability of response to red blood cell transfusion and to predict which
      patients will have an Hgb rise higher or lower than that predicted by the long
      standing convention of "one and three". This was a retrospective chart review in
      a single hospital. Data for 167 consecutive patient encounters were reviewed. The
      dataset was randomly divided into derivation and validation subsets with no
      significant differences in characteristics. DeltaHgb was defined as
      posttransfusion Hgb minus pre-transfusion Hgb per red blood cell unit. We
      classified all the patients in both the subsets as "high responders" (DeltaHgb >1
      g/dL) or as "low responders" (DeltaHgb <=1 g/dL). In univariate analysis, age,
      sex, body weight, estimated blood volume, and body surface area were
      significantly associated with response category (P<0.05). Different multivariate
      regression models were tested using the derivation subset. The probability of
      being a high responder was best calculated using the logarithmic formula eH / (1
      + eH), where H is B0 + (B1 * variable 1) + (B2 * variable 2). Bis are
      coefficients of the models. On validation, the model H=6.5-(3.3 * body surface
      area), with the cutoff probability of 0.5, was found to correctly classify
      patients into high and low responders in 69% of cases (sensitivity 84.6%,
      specificity 43.8%). This model may equip clinicians to make more appropriate
      transfusion decisions and serve as a springboard for further research in
      transfusion medicine.

PMID- 27703401
TI  - Mentoring in higher education.

PMID- 27703402
TI  - Job satisfaction among community pharmacy professionals in Mekelle city, Northern
      Ethiopia.
AB  - INTRODUCTION: Job satisfaction is a multidimensional, enduring, important, and
      much-researched concept in the field of organizational behavior and has been
      identified as recognition in one's field of work, level of salary, opportunities
      for promotion, and achievement of personal goals. Job satisfaction directly
      affects the labor market behavior and economic efficiency by means of the impact
      on productivity and turnover of staff. The aim of this study was to assess the
      satisfaction level of pharmacy professionals in Mekelle city. METHODS: This
      institution-based cross-sectional study was conducted as a survey and only
      included voluntary participants. Those participants who did not volunteer to
      participate were excluded from the study. A structured questionnaire was used as
      a data collection tool; it was developed from different literature in the English
      language, and then the original tool was translated to the local language for the
      purpose of understanding. RESULTS: In Mekelle, ~100 pharmacy professionals work
      in private medicine retail outlets. From those, only 60 volunteered to
      participate in this study. Significant difference in job satisfaction and job
      stress were observed between those working full-time and part-time, with P-values
      of 0.031 and 0.021, respectively. CONCLUSION: From the findings of the current
      study, it can be concluded that around two-thirds of pharmacy professionals in
      Mekelle city were satisfied with their professional practice.

PMID- 27703398
TI  - Cystic fibrosis transmembrane conductance regulator modulators in cystic
      fibrosis: current perspectives.
AB  - Mutations of the CFTR gene cause cystic fibrosis (CF), the most common recessive
      monogenic disease worldwide. These mutations alter the synthesis, processing,
      function, or half-life of CFTR, the main chloride channel expressed in the apical
      membrane of epithelial cells in the airway, intestine, pancreas, and reproductive
      tract. Lung disease is the most critical manifestation of CF. It is characterized
      by airway obstruction, infection, and inflammation that lead to fatal tissue
      destruction. In spite of great advances in early and multidisciplinary medical
      care, and in our understanding of the pathophysiology, CF is still considerably
      reducing the life expectancy of patients. This review highlights the current
      development in pharmacological modulators of CFTR, which aim at rescuing the
      expression and/or function of mutated CFTR. While only Kalydeco(r) and Orkambi(r)
      are currently available to patients, many other families of CFTR modulators are
      undergoing preclinical and clinical investigations. Drug repositioning and
      personalized medicine are particularly detailed in this review as they represent
      the most promising strategies for restoring CFTR function in CF.

PMID- 27703404
TI  - Serological evidence of equine influenza virus in horse stables in Kaduna,
      Nigeria.
AB  - Equine influenza virus (EIV) is a major cause of acute respiratory diseases in
      horses in most parts of the world that results in severe economic losses.
      Information on the epidemiology of EIV in tropical Africa is scanty. An enzyme
      linked immunosorbent assay (ELISA) was used to detect the presence of influenza A
      virus nucleoprotein (NP) in 284 horse sera in Kaduna State, Northern Nigeria. The
      ELISA-positive sera were further examined for hemagglutination inhibition (HI)
      antibodies to two strains each of H3N8 and H7N3 subtypes of influenza A virus.
      The results showed that antibodies against influenza A virus nucleoprotein were
      detected in 60.9% (173 of 284) of horses examined by NP-ELISA. Equine H3 and H7
      subtypes were detected in 60% (21 of 35) and 20% (7 of 35) of horse sera
      respectively across the stables. Adequate quarantine of all imported horses, a
      national equine influenza surveillance plan and an appropriate EIV control
      program in Nigeria are recommended to safeguard the large horse population.

PMID- 27703403
TI  - Epidemiology of racing injuries in Thoroughbred racehorses with special reference
      to bone fractures: Japanese experience from the 1980s to 2000s.
AB  - This report describes the descriptive epidemiology of racing fractures that
      occurred from the 1980s to 2000s on racetracks of the Japan Racing Association
      (JRA). The incidence of racehorse fractures during flat racing was approximately
      1-2%. Fractures occurring during a race are more likely to occur in a forelimb.
      Fractures mostly occur at the third and fourth corners of oval tracks and on the
      home stretch. They also occur more frequently at the time of changing the leading
      limb. Comparison of the incidence of racing fracture between before and after
      reconstruction of the geometrical configuration of a racetrack revealed that
      there was an outstanding reduction in the number of serious fractures in the year
      before and after reconstruction. It was postulated that the improvement in racing
      time, possibly influenced by reconstructing the geometrical configuration of the
      racetrack, was connected to the reduction in the number of fractures. Of non
      biological race- and course-related factors, type of course (dirt or turf), track
      surface condition, differences between racecourses, and racing distance
      significantly influence racing time. By using an instrumented shoe, vertical
      ground reaction forces (VGRFs) on the forelimb during galloping and the
      relationships between a rough dirt and woodchip track surface and a smooth dirt
      and woodchip surface were measured. Relating the incidence of racing fractures
      with track conditions in general showed that track surface has significant
      effects on the incidence of fracture, with the incidence of fractures increasing
      as track conditions on dirt worsen and a tendency for the incidence of fractures
      to decrease as track conditions on turf worsen. It seems probable that track
      condition in general may affect the incidence of fracture. The incidence of
      fracture in horses during both racing and training decreased as the years
      progressed.

PMID- 27703406
TI  - Autopsy imaging for cardiac tamponade in a Thoroughbred foal.
AB  - Autopsy imaging (Ai), postmortem imaging before necropsy, is used in human
      forensic medicine. Ai was performed using computed tomography (CT) for a 1-month
      old Thoroughbred foal cadaver found in a pasture. CT revealed pericardial
      effusion, collapse of the aorta, bleeding in the lung lobe, gas in the ventricles
      and liver parenchyma, and distension of the digestive tract. Rupture in the left
      auricle was confirmed by necropsy; however, it was not depicted on CT. Therefore,
      Ai and conventional necropsy are considered to complement each other. The cause
      of death was determined to be traumatic cardiac tamponade. In conclusion, Ai is
      an additional option for determining cause of death.

PMID- 27703405
TI  - Sequence variants of BIEC2-808543 near LCORL are associated with body composition
      in Thoroughbreds under training.
AB  - Ligand-dependent nuclear receptor compressor-like (LCORL) encodes a transcription
      factor, and its polymorphisms are associated with measures of skeletal frame size
      and adult height in several species. Recently, the single nucleotide polymorphism
      (SNP) BIEC2-808543 located upstream of LCORL was identified as a genetic
      diagnostic marker associated with withers height in Thoroughbreds. In this study,
      322 Thoroughbreds-in-training were genotyped for BIEC2-808543 to evaluate the
      association between genotype and body composition traits, including body weight,
      withers height, the ratio of body weight to withers height, chest circumference,
      and cannon circumference. Of these, withers height and cannon circumference were
      significantly associated with LCORL genotypes throughout almost the entire
      training period in males and females. Animals with a C/T genotype had higher
      withers height (maximum differences of 1.8 cm and 2.1 cm in males and females,
      respectively) and cannon circumstance (maximum differences of 0.65 cm and 0.48 cm
      in males and females, respectively) compared with animals with a T/T genotype.
      These results suggested that the regulation of LCORL expression influences the
      skeletal frame size in Thoroughbreds and thus, indirectly affects the body
      weight. Although LCORL and BIEC2-808543 would be useful for selective breeding in
      Thoroughbreds, the production of genetically modified animals and gene doping
      based on genetic information should be prohibited in order to maintain racing
      integrity.

PMID- 27703407
TI  - Four cases of equine motor neuron disease in Japan.
AB  - In this study, fasciculation of the limbs and tongue was observed in four horses
      kept by a riding club. Neurogenic muscle atrophy was also observed in biopsy of
      pathological tissues. In addition, in two cases that subjected to autopsy, Bunina
      like bodies of inclusion in the cell bodies of neurons in the spinal cord ventral
      horn were confirmed, leading to a diagnosis of equine motor neuron disease
      (EMND). Serum vitamin E concentrations varied between 0.3 and 0.4ug/ml, which is
      significantly lower than the levels in normal horses. Although lack of vitamin E
      is speculated to be a contributory factor for development of EMND, no significant
      improvement was observed following administration of vitamin E.

PMID- 27703408
TI  - Reference range of blood biomarkers for oxidative stress in Thoroughbred
      racehorses (2-5 years old).
AB  - The oxidant and antioxidant equilibrium is known to play an important role in
      equine medicine and equine exercise physiology. There are abundant findings in
      this field; however, not many studies have been conducted for reference ranges of
      oxidative stress biomarkers in horses. This study was conducted to determine the
      reference values of reactive oxygen metabolites (d-ROMs) and biological
      antioxidant potential (BAP) using blood samples from 372 (191 males, 181 females)
      Thoroughbred racehorse aged 2 to 5 (3.43 +/- 1.10 (mean +/- SD)) years old. There
      were obvious gender differences in oxidative biomarkers, and growth/age-related
      changes were observed especially in females. Gender and age must be considered
      when interpreting obtained oxidative stress biomarkers for diagnosis of disease
      or fitness alterations in Thoroughbred racehorses.

PMID- 27703411
TI  - Phillip D. Wilson, Jr., MD: A Life Fulfilled.

PMID- 27703409
TI  - Current Immunotherapies for Sarcoma: Clinical Trials and Rationale.
AB  - Sarcoma tumors are rare and heterogeneous, yet they possess many characteristics
      that may facilitate immunotherapeutic responses. Both active strategies including
      vaccines and passive strategies involving cellular adoptive immunotherapy have
      been applied clinically. Results of these clinical trials indicate a distinct
      benefit for select patients. The recent breakthrough of immunologic checkpoint
      inhibition is being rapidly introduced to a variety of tumor types including
      sarcoma. It is anticipated that these emerging immunotherapies will exhibit
      clinical efficacy for a variety of sarcomas. The increasing ability to tailor
      immunologic therapies to sarcoma patients will undoubtedly generate further
      enthusiasm and clinical research for this treatment modality.

PMID- 27703412
TI  - All-Arthroscopic Modified Rotator Interval Slide for Massive Anterosuperior Cuff
      Tears Using the Subdeltoid Space: Surgical Technique and Early Results.
AB  - BACKGROUND: Traditional intra-articular arthroscopic repair techniques for
      massive anterosuperior rotator cuff tears are technically demanding and
      necessitate sacrifice of the rotator interval to enable visualization. An
      interval slide allows mobilization through release of the medial aspect of the
      rotator interval, while leaving the lateral, bridging fibers intact.
      QUESTIONS/PURPOSES: The purpose of this study was to report a novel,
      arthroscopic, open-equivalent technique using the subdeltoid space to address
      these tears along with early clinical results. METHODS: A retrospective review of
      prospectively collected data identified 11 consecutive arthroscopic massive
      anterosuperior rotator cuff repairs with a concomitant biceps tenodesis performed
      by the senior surgeon using a uniform technique. Outcome measures included range
      of motion, visual analog scale for pain, rotator cuff strength, American Shoulder
      and Elbow Surgeons (ASES) outcome scale, and Short Form-12 (SF-12). RESULTS:
      Average length of follow-up was 22.2 months (range 12.5-30.0 months). Visual
      analog scale (VAS) pain scores, ASES, and SF-12 all demonstrated significant
      improvement from pre-op to final follow-up from 6.2 to 0.9 (p < 0.05), 27.4 to
      82.8 (p < 0.05), and 26.6 to 45.5 (p < 0.05) respectively. Average forward
      flexion improved from 145 degrees  to 160 degrees  (p < 0.05). Seven of the nine
      patients with a positive preoperative belly press had a negative test at final
      follow-up. Nine of the 10 patients with a positive lift off test demonstrated a
      negative test on final follow-up. Ninety-one percent reported they were satisfied
      with their outcome. CONCLUSIONS: The described modified all-arthroscopic
      subdeltoid approach for anterosuperior cuff repairs enabled an open-equivalent
      interval slide technique that preserved the bridging lateral fibers of the
      rotator interval and demonstrated promising early-term clinical results.

PMID- 27703410
TI  - Fundamental Characteristics of AAA+ Protein Family Structure and Function.
AB  - Many complex cellular events depend on multiprotein complexes known as molecular
      machines to efficiently couple the energy derived from adenosine triphosphate
      hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase
      superfamily (ATPases Associated with various cellular Activities) are critical
      components of many molecular machines. AAA+ proteins are defined by conserved
      modules that precisely position the active site elements of two adjacent subunits
      to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure
      that translocates a polymeric substrate through the central channel using
      specialized loops that project into the central channel. We discuss the major
      features of AAA+ protein structure and function with an emphasis on pivotal
      aspects elucidated with archaeal proteins.

PMID- 27703413
TI  - The Quality of Open-Access Video-Based Orthopaedic Instructional Content for the
      Shoulder Physical Exam is Inconsistent.
AB  - BACKGROUND: The internet has an increasing role in both patient and physician
      education. While several recent studies critically appraised the quality and
      accuracy of web-based written information available to patients, no studies have
      evaluated such parameters for open-access video content designed for provider
      use. QUESTIONS/PURPOSES: The primary goal of the study was to determine the
      accuracy of internet-based instructional videos featuring the shoulder physical
      examination. METHODS: An assessment of quality and accuracy of said video content
      was performed using the basic shoulder examination as a surrogate for the "best
      case scenario" due to its widely accepted components that are stable over time.
      Three search terms ("shoulder," "examination," and "shoulder exam") were entered
      into the four online video resources most commonly accessed by orthopaedic
      surgery residents (VuMedi, G9MD, Orthobullets, and YouTube). Videos were captured
      and independently reviewed by three orthopaedic surgeons. Quality and accuracy
      were assessed in accordance with previously published standards. RESULTS: Of the
      39 video tutorials reviewed, 61% were rated as fair or poor. Specific maneuvers
      such as the Hawkins test, O'Brien sign, and Neer impingement test were accurately
      demonstrated in 50, 36, and 27% of videos, respectively. Inter-rater reliability
      was excellent (mean kappa 0.80, range 0.79-0.81). CONCLUSION: Our results suggest
      that information presented in open-access video tutorials featuring the physical
      examination of the shoulder is inconsistent. Trainee exposure to such potentially
      inaccurate information may have a significant impact on trainee education.

PMID- 27703414
TI  - Normal Femorotibial Rotational Alignment and Implications for Total Knee
      Arthroplasty: an MRI Analysis.
AB  - BACKGROUND: Rotational alignment of prosthetic components in total knee
      arthroplasty (TKA) is important to successful outcomes. Component malrotation is
      a known cause of revision and understanding normal rotational alignment may help
      recreate normal joint kinematics. To date, no large MRI study assessing
      femorotibial rotational alignment in nonarthritic knees has been undertaken.
      QUESTIONS/PURPOSES: Is Insall's tibial axis a reliable rotational landmark
      against common femoral rotational axes in the nonarthritic patient population?
      METHODS: We reviewed 544 knee MRI scans performed for suspected soft tissue
      pathology and identified Insall's tibial rotational axis as well as the femoral
      clinical trans-epicondylar axis (TEAc), femoral surgical trans-epicondylar axis
      (TEAs), posterior condylar articular axis (PCA), and a modified Eckhoff's
      cylindrical axis. The perpendiculars of these axes were superimposed on Insall's
      tibial axis, and the angular differences were measured. RESULTS: Insall's axis
      was internally rotated to the TEAc by 1.4 degrees , externally rotated to
      Eckhoff's cylindrical axis by 1.8 degrees , externally rotated to the TEAs by 2.7
      degrees , and externally rotated to the PCA by 3.5 degrees . The mean deviation
      from 0 degrees  (optimal alignment for each femoral axis) was significantly
      greater for the PCA relative to all other femoral axis. CONCLUSION: Insall's axis
      is a reliable landmark for rotational positioning of the tibial component and may
      optimize femorotibial kinematics in fixed-bearing TKA.

PMID- 27703415
TI  - Handheld Navigation Device and Patient-Specific Cutting Guides Result in Similar
      Coronal Alignment for Primary Total Knee Arthroplasty: a Retrospective Matched
      Cohort Study.
AB  - BACKGROUND: Proper alignment of total knee arthroplasty (TKA) is essential for
      TKA function and may reduce the risk of aseptic failure. Technologies that
      prevent malalignment may reduce the risk of revision surgery. QUESTIONS/PURPOSES:
      The purpose of this study was to compare two competing TKA systems that purport
      improved alignment: patient-specific instrumentation (PSI), and a handheld
      portable navigation device (NAV). METHODS: After IRB approval, 49 consecutive PSI
      TKAs (40 patients) were matched based on preoperative characteristics to 49 NAV
      TKAs (40 patients) performed by a single surgeon. A blinded observer measured
      alignment on digital radiographs. Operating room records were reviewed for
      procedure times. Two-tailed paired sample t tests and McNemar's test were used as
      appropriate. Alpha level was 0.05 for all tests. RESULTS: Preoperative cohort
      characteristics were not different. Mean postoperative long-leg mechanical
      alignment was within +/-1 degrees  of neutral for both groups, although
      statistically different (p = 0.026). There were no other significant differences
      in coronal alignment. PSI exhibited significantly greater posterior tibial slope
      (4.4 degrees ) compared to NAV (2.7 degrees ) (p = 0.004); PSI resulted in
      significantly more outliers (>6 degrees ; p = 0.004). Procedure time for
      unilateral TKAs was lower for PSI (74.4 min) compared to that for NAV (80.6 min;
      p = 0.023). CONCLUSION: NAV and PSI technologies provided excellent coronal plane
      alignment. NAV was better for sagittal tibial slope, while PSI procedure times
      were shorter for unilateral TKA. The impact of these technologies on patient
      reported outcomes and TKA survivorship is controversial and should be the focus
      of future research.

PMID- 27703416
TI  - ACL Damage and Deficiency is Associated with More Severe Preoperative Deformity,
      Lower Range of Motion at the Time of TKA.
AB  - BACKGROUND: ACL status varies in the arthritic knee during TKA.
      QUESTIONS/PURPOSES: The purpose of this study was to examine clinical features
      and intraoperative findings associated with stages of ACL degeneration. METHODS:
      Coronal deformity, ROM, intra-articular degenerative patterns, and ligament
      releases were assessed for 1656 knees during TKA. Common patterns of deformity
      and severity of degenerative change were assessed as a function of the severity
      of ACL deficiency. RESULTS: Of the 1656 knees assessed, 27% had a normal ACL, 55%
      exhibited damage, and 18% exhibited complete absence of the ACL. Increased
      coronal deformity and lower preoperative ROM was associated with ACL deficiency.
      Increased chondral and meniscal damage and more extensive osteophyte formation
      were also found. More extensive ligament releases were required in ACL-deficient
      knees. CONCLUSIONS: The status of the ACL is predictive of the need for increased
      surgical deformity correction. A better understanding of ACL status is an
      important consideration during in choosing TKA as opposed to unicompartmental
      arthroplasty. The status of the ACL should be considered in planning for implant
      choice in TKA.

PMID- 27703417
TI  - Higher Acetabular Anteversion in Direct Anterior Total Hip Arthroplasty: A
      Retrospective Case-Control Study.
AB  - BACKGROUND: Surgical approach is known as a risk factor that influences cup
      malposition while performing total hip arthroplasty (THA). However, no study has
      been conducted comparing cup positioning between the supine direct anterior (DA)
      and supine direct lateral (DL) THA approaches. QUESTIONS/PURPOSES: (1) Is there a
      difference in acetabular cup positioning between supine DA and supine DL THA
      approaches? (2) Are there differences in complications based on acetabular cup
      positioning between the two approaches? METHODS: From 2012 to 2014, 186 patients
      who underwent primary THAs using DA approach were matched with 186 patients using
      DL approach by body mass index, age, and gender. Cup anteversion and abduction
      angles were measured from standing anteroposterior pelvis radiographs by two
      blinded observers. The Lewinnek safe zone was used as the standard for cup
      positioning. Cup anteversion, abduction angles, and complications were recorded
      and compared. RESULTS: Cup anteversion was on average 3 degrees  higher in the DA
      approach compared to the DL approach. The abduction angle for the DA approach was
      equivalent to the DL approach both averaging 46 degrees  to 47 degrees . There
      were more DA hips outside of the safe zone (10%) for anteversion than DL (3%)
      hips. There were no differences in complications between DA and DL approaches.
      CONCLUSION: There is a tendency to antevert the acetabular cup when performing
      THAs using the DA approach, and one must be mindful of this when implanting the
      acetabular component.

PMID- 27703418
TI  - Association between Achilles tightness and lower extremity injury in children.
AB  - BACKGROUND: It is unclear whether isolated gastroc/soleus tightness can increase
      the risk of lower extremity injury in an otherwise healthy child.
      QUESTIONS/PURPOSES: (1) Is there a difference in gastroc/soleus tightness, as
      represented by ankle dorsiflexion with the knee extended, in children presenting
      with upper versus lower extremity complaints? (2) Is there a difference in
      gastroc/soleus tightness in children presenting with atraumatic versus traumatic
      lower extremity complaints? METHODS: We performed a cross-sectional study of 206
      consecutive walking age children presenting to a county orthopedic clinic with
      new upper or lower extremity complaints. Passive ankle dorsiflexion was measured
      based on the lateral border of the foot versus the anterior lower leg with the
      knee fully extended and the foot in inversion. RESULTS: Average age was 10.0 +/-
      4.5 years. In the 117 patients presenting with upper extremity complaints, ankle
      dorsiflexion was 15.0 degrees  +/- 11.6 degrees . Of the lower extremity
      patients, 40 presented without trauma, with dorsiflexion of 11.8 degrees  +/-
      14.5 degrees , while 49 presented with trauma, with dorsiflexion of 6.5 degrees 
      +/- 12.0 degrees . Multiple regression analysis found significantly decreased
      ankle dorsiflexion with increasing age and in the lower extremity trauma group.
      Twelve percent of upper extremity patients had 0 degrees  or less of
      dorsiflexion, as compared to 25% of lower extremity nontrauma patients and 41% of
      lower extremity trauma patients. CONCLUSIONS: Patients presenting with lower
      extremity trauma had significantly more gastroc/soleus tightness in their well
      leg than patients presenting with upper extremity complaints. Gastroc/soleus
      tightness may present a simple target for reducing lower extremity injury rates
      in children.

PMID- 27703419
TI  - Spontaneous Fractures of a Modern Modular Uncemented Femoral Stem.
AB  - BACKGROUND: Femoral stem fracture following total hip arthroplasty is an uncommon
      event that requires immediate revision surgery. QUESTIONS/PURPOSES: We report on
      four patients who experienced stem fractures of one design and a review of the US
      Food and Drug Administration adverse event reports on this design. METHODS:
      Fracture surfaces of four EMPERIONTM (Smith & Nephew, Memphis, TN) femoral stems
      were analyzed under optical and scanning electron microscopy. A search of the
      FDA's Manufacturer and User Facility Device Experience (MAUDE) that reports on
      all EMPERIONTM adverse events was completed. RESULTS: Fracture surfaces exhibited
      characteristics consistent with a fatigue fracture mechanism. Sixteen MAUDE
      reports claimed stem fracture or breakage of EMPERIONTM stems. CONCLUSION: The
      four cases of EMPERIONTM stem fractures were likely driven by small stem
      diameter, high offset, and high patient weight. Modular stem-sleeve femoral
      systems are susceptible to fatigue failure under high stress and should only be
      used in appropriate patients, whom are not considered obese.

PMID- 27703420
TI  - Musculoskeletal Involvement in SSc Is Associated with Worse Scores on Short Form
      36 and Scleroderma Health Assessment Questionnaire and Lower Tumor Necrosis
      Factor-alpha Gene Expression in Peripheral Blood Mononuclear Cells.
AB  - BACKGROUND: Systemic sclerosis (SSc) is characterized by a wide variety of
      symptoms and disease manifestations including joint pain, gastrointestinal
      dysfunction, interstitial lung disease, and cardiomyopathy. QUESTIONS/PURPOSES:
      Using the Scleroderma Health Assessment Questionnaire (SHAQ) and Short Form-36
      (SF-36) we explored how patient-reported physical health, mental health, and
      functional status related to these clinical characteristics and to cytokine
      levels utilizing the Hospital for Special Surgery Scleroderma Registry. METHODS:
      In a cross-sectional study of 185 patients meeting the 2013 ACR/EULAR criteria
      for SSc, we compared disease features and patient-reported outcomes (PROs).
      Interleukin-6 (IL-6), interleukin-1beta (IL1beta), and tumor necrosis factor
      alpha (TNFalpha) levels were assessed by luminex and ELISA assays in a subset of
      32 patients. The Pearson correlation coefficient, Spearman correlation
      coefficient, two-sample t test or Wilcoxon rank sum test, ANOVA or Kuskal-Wallis
      test, and Pearson chi-squared or Fisher's exact test were performed as applicable
      to detect the association between disease manifestations, PROs, and blood
      biomarkers. RESULTS: The modified Rodnan skin score (MRSS) was positively
      correlated with SHAQ scores. Patients who had musculoskeletal involvement scored
      worse on both the SHAQ and SF-36. Lower levels of TNFalpha expression in PBMCs
      were also correlated with musculoskeletal involvement. No other significant
      correlations were found between clinical factors, PROs, and cytokine data.
      CONCLUSION: Musculoskeletal outcomes are a major determinant of quality of life
      and function in patients with SSc. These results emphasize the importance of
      musculoskeletal outcomes in clinical studies of SSc.

PMID- 27703421
TI  - Treatment of Pre-Collapse Stages of Osteonecrosis of the Femoral Head: a
      Systematic Review of Randomized Control Trials.
AB  - BACKGROUND: Treatment for osteonecrosis of the femoral head (ONFH) remains
      controversial. Current reviews include low-level evidence studies evaluating the
      treatment of both pre-collapse and collapse stages of the disease.
      QUESTIONS/PURPOSES: The purpose of the current study is to systematically review
      the literature evaluating core decompression (CD) with bone marrow mesenchymal
      cells (BMMCs), CD alone, and bisphosphonate treatment in pre-collapse ONFH by
      focusing just on randomized clinical trials (RCTs) reporting functional and
      radiologic outcomes. We aim to determine if the literature provides evidence
      supporting any single approach. METHODS: Using PubMed and EMBASE databases, we
      reviewed the clinical evidence of treatments for pre-collapse ONFH following
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines. Twelve RCTs met the inclusion criteria. RESULTS: Results showed that
      CD with BMMCs has lower risk of femoral head collapse when compared to the CD
      alone excluding hips lost to follow-up (relative risk (RR) [95% CI]:0.25 [0.11,
      0.60]; p = 0.002) and when assumed that hips lost to follow-up experienced
      collapse (RR [95% CI]: 0.11 [0.03, 0.47]; p = 0.003). Neither CD nor
      bisphosphonate treatments showed lower risk to femoral head collapse when
      compared to control treatments (p = 0.46 and 0.31, respectively). CONCLUSION:
      Current literature shows that there is a lower risk of femoral head collapse in
      patients with ONFH treated with CD combined with BMMCs when compared to CD alone;
      however, there is no robust evidence to determine the effect on functional
      outcomes. More RCTs assessing new combination therapies and using standardized
      outcome measures are required.

PMID- 27703422
TI  - Rating a Sports Medicine Surgeon's "Quality" in the Modern Era: an Analysis of
      Popular Physician Online Rating Websites.
AB  - BACKGROUND: Consumer-driven healthcare and an increasing emphasis on quality
      metrics have encouraged patient engagement in the rating of healthcare. As such,
      online physician rating websites have become mainstream and may play a potential
      role in future healthcare policy. QUESTIONS/PURPOSES: The purpose of this study
      was to evaluate online patient ratings for US sports medicine surgeons, determine
      predictors of positive ratings and analyze for inter-website scoring correlation.
      METHODS: The American Orthopedic Society for Sports Medicine (AOSSM) member
      directory was sampled. Surgeon demographic and rating data were searched on three
      online physicians rating websites: HealthGrades.com (HG), RateMDs.com (RM) and
      Vitals.com (V). Written rating comments were categorized as relating to the
      following: surgeon competence, surgeon affability and process of care. Bivariate
      linear regression, Pearson correlation and multivariable analyses were used to
      determine factors associated with positive ratings. RESULTS: Two hundred seventy
      five sports medicine surgeons were included. Two hundred seventy-one (99%) had
      ratings on at least one of the three websites. Sports surgeons were rated highly
      across all three websites (mean >4.0/5); however, there was only a low to
      moderate degree of correlation among websites. On HG, female surgeons and
      surgeons in academia were more likely to receive higher overall ratings. Across
      all three websites, increased number of years in practice inversely correlated
      with ratings; this relationship neared significance for HG and was significant
      for RM. A surgeon's online presence or geographic location was not associated
      with higher ratings. In multivariable regression analysis for ratings on HG,
      female sex was the only significant predictor of higher ratings. Two thousand
      three hundred forty-one written comments were analyzed: perceived surgeon
      competence and communication influenced the direction of ratings for the top and
      bottom tier surgeons. CONCLUSION: There was a low degree of correlation among
      online websites for surgeon ratings. Female surgeons and those with fewer years
      in practice appear to have higher ratings on these websites; comment content
      analysis suggests that high and low ratings are influenced by perceived surgeon
      competence and affability.

PMID- 27703423
TI  - Cervical Spondylodiscitis After Oxygen-Ozone Therapy for Treatment of a Cervical
      Disc Herniation: a Case Report and Review of the Literature.

PMID- 27703424
TI  - Hypertrophic Osteoarthropathy: an Unusual Cause of Knee Pain and Recurrent
      Effusion.

PMID- 27703425
TI  - Displaced Proximal Humerus Fractures: is a Sling as Good as a Plate?
AB  - The treatment of displaced proximal humerus fractures is challenging and complex,
      as its success is predicated on multiple factors. While it is clear that a
      majority of proximal humerus fractures may be treated nonoperatively, it is less
      clear which patients benefit from surgical management. The PROFHER trial, a
      randomized controlled study, used patient-reported outcomes to compare surgical
      to nonsurgical management of displaced proximal humerus fractures. The purpose of
      this review is to highlight the strengths and weaknesses of the PROFHER trial and
      to assess the validity of its conclusion in the context of existing literature.
      The authors found no difference in the Oxford Shoulder Score (OSS) between the
      surgical and nonsurgical groups. Additionally, no difference was found between
      groups in any of the secondary outcomes, which included the Short-Form 12 (SF-12)
      health survey, surgical and fracture-related complications, additional surgery or
      therapy, inpatient medical complications, and mortality. They concluded that the
      recent increase in surgical management of proximal humerus fractures is perhaps
      unwarranted. While the randomization was successful and the pragmatic design may
      enable greater generalizability, this study possesses numerous flaws inherent in
      such an ambitious endeavor, including an inability to identify specific factors
      which explain the lack of superiority of surgical management. Despite its
      weaknesses, this study is a valuable datapoint which encourages surgeons to
      reexamine their surgical indications for this injury.

PMID- 27703426
TI  - Further Research Is Needed to Define the Benefits of Non-operative Rotator Cuff
      Treatment.
AB  - Kukkonen et al.'s "Treatment of Nontraumatic Rotator Cuff Tears: A Randomized
      Controlled Trial with Two Years of Clinical and Imaging Follow-up" compared the
      efficacy of physical therapy, acromioplasty, and rotator cuff repair for the
      treatment of degenerative supraspinatus tendon tears in patients aged over 55.
      This review examines the authors' findings and their implications on clinical
      practice. Kukkonen et al. reported no significant difference in clinical outcome
      among patients treated operatively versus non-operatively for degenerative
      rotator cuff tears. The authors concluded that non-operative treatment is an
      appropriate option for patients aged 55 or older. Rotator cuff treatment outcomes
      are closely linked to patient age, and while this level I study found no evidence
      of a benefit of surgical treatment, the age range in the studied demographic was
      perhaps too wide to draw generalizable conclusions. Furthermore, 2-year follow-up
      may be inadequate to fully demonstrate the differences in outcomes between these
      treatment options.

PMID- 27703427
TI  - Erratum to: Clinical Results and Failure Mechanisms of a Nonmodular Constrained
      Knee Without Stem Extensions.
AB  - [This corrects the article DOI: 10.1007/s11420-012-9277-9.].

PMID- 27703428
TI  - Solitary Langerhans cell histiocytosis of the hard palate: a diagnostic pitfall.
AB  - Langerhans cell histiocytosis (LCH) is a relatively rare and unique disease
      characterized by an abnormal proliferation of immature dendritic cells. It is
      predominantly seen in children with adults showing less than ten times the
      incidence compared to childhood. The clinical presentation and organ involvement
      is highly variable. Oral manifestations generally consist of mucosal ulceration
      associated with lesions of the underlying bone. Lesions limited to the oral
      mucosa are rare. We present a case of a 45-year-old male who presented with an
      ulcer on the hard palate showing histopathologic features of LCH. The present
      case is a reminder of the possibility of occurrence of this unusual entity in the
      oral cavity. Appropriate use of immunohistochemistry is advocated to avoid
      diagnostic pitfalls.

PMID- 27703429
TI  - Amygdalar Auditory Neurons Contribute to Self-Other Distinction during Ultrasonic
      Social Vocalization in Rats.
AB  - Although, clinical studies reported hyperactivation of the auditory system and
      amygdala in patients with auditory hallucinations (hearing others' but not one's
      own voice, independent of any external stimulus), neural mechanisms of self/other
      attribution is not well understood. We recorded neuronal responses in the dorsal
      amygdala including the lateral amygdaloid nucleus to ultrasonic vocalization
      (USVs) emitted by subjects and conspecifics during free social interaction in 16
      adult male rats. The animals emitting the USVs were identified by EMG recordings.
      One-quarter of the amygdalar neurons (15/60) responded to 50 kHz calls by the
      subject and/or conspecifics. Among the responsive neurons, most neurons (Type
      Other neurons; 73%, 11/15) responded only to calls by conspecifics but not
      subjects. Two Type-Self neurons (13%, 2/15) responded to calls by the subject but
      not those by conspecifics, although their response selectivity to subjects vs.
      conspecifics was lower than that of Type-Other neurons. The remaining two neurons
      (13%) responded to calls by both the subject and conspecifics. Furthermore,
      population coding of the amygdalar neurons represented distinction of subject vs.
      conspecific calls. The present results provide the first neurophysiological
      evidence that the amygdala discriminately represents affective social calls by
      subject and conspecifics. These findings suggest that the amygdala is an
      important brain region for self/other attribution. Furthermore, pathological
      activation of the amygdala, where Type-Other neurons predominate, could induce
      external misattribution of percepts of vocalization.

PMID- 27703430
TI  - Early Impairment of Synaptic and Intrinsic Excitability in Mice Expressing
      ALS/Dementia-Linked Mutant UBQLN2.
AB  - Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are
      believed to represent the different outcomes of a common pathogenic mechanism.
      However, while researchers have intensely studied the involvement of motor
      neurons in the ALS/FTD syndrome, very little is known about the function of
      hippocampal neurons, although this area is critical for memory and other
      cognitive functions. We investigated the electrophysiological properties of CA1
      pyramidal cells in slices from 1 month-old UBQLN2P497H mice, a recently generated
      model of ALS/FTD that shows heavy depositions of ubiquilin2-positive aggregates
      in this brain region. We found that, compared to wild-type mice, cells from
      UBQLN2P497H mice were hypo-excitable. The amplitude of the glutamatergic currents
      elicited by afferent fiber stimulation was reduced by ~50%, but no change was
      detected in paired-pulse plasticity. The maximum firing frequency in response to
      depolarizing current injection was reduced by ~30%; the fast
      afterhyperpolarization in response to a range of depolarizations was reduced by
      almost 10 mV; the maximum slow afterhyperpolarization (sAHP) was also
      significantly decreased, likely in consequence of the decreased number of spikes.
      Finally, the action potential (AP) upstroke was blunted and the threshold
      depolarized compared to controls. Thus, synaptic and intrinsic excitability are
      both impaired in CA1 pyramidal cells of UBQLN2P497H mice, likely constituting a
      cellular mechanism for the cognitive impairments. Because these alterations are
      detectable before the establishment of overt pathology, we hypothesize that they
      may affect the further course of the disease.

PMID- 27703431
TI  - Cistanches Herba: A Neuropharmacology Review.
AB  - Cistanches Herba (family Orobanchaceae), commonly known as "desert ginseng" or
      Rou Cong Rong, is a global genus and commonly used for its neuroprotective,
      immunomodulatory, anti-oxidative, kidney impotence, laxative, anti-inflammatory,
      hepatoprotective, anti-bacterial, anti-viral, and anti-tumor effects in
      traditional herbal formulations in North Africa, Arabic, and Asian countries. The
      major bioactive compound present in this plant is phenylethanoid glycosides. In
      recent years, there has been great important in scientific investigation of the
      neuropharmacological effects of the bioactive compounds. The in vitro and in vivo
      studies suggests these compounds demonstrate neuropharmacological activities
      against a wide range of complex nervous system diseases which occurs through
      different mechanisms include improving immunity function and kidney aging, anti
      lipid peroxidation, scavenging free radical, inducing the activation of caspase-3
      and caspase-8. This review aims to summaries the various neuropharmacological
      effects and mechanisms of Cistanches Herba extracts and related compounds,
      including its efficacy as a cure for Alzheimer's disease and Parkinson's disease
      with reference to the published literature. Which provides guidance for further
      research on the clinical application of Cistanches Herba.

PMID- 27703432
TI  - Linezolid Toxicity and Mitochondrial Susceptibility: A Novel Neurological
      Complication in a Lebanese Patient.
AB  - The recent rise in the use of linezolid to treat a variety of resistant pathogens
      has uncovered many side effects. Some patients develop lactic acidosis,
      myelosuppression, optic or peripheral neuropathies, and myopathies. We evaluated
      an elderly patient who presented to the Emergency Room with linezolid toxicity
      and a novel neurologic complication characterized by bilateral globi pallidi
      necrosis. Mitochondrial ribosome inhibition was described to be the predisposing
      factor. The patient belongs to the mitochondrial J1 haplotype known to be
      associated with side effects of the drug. We recommend based on the molecular
      profile of the illness pretreatment considerations and complication management.

PMID- 27703433
TI  - Corrigendum: Discoidin Domain Receptors: Potential Actors and Targets in Cancer.
AB  - [This corrects the article on p. 55 in vol. 7, PMID: 27014069.].

PMID- 27703436
TI  - Erratum: The Genetic Intersection of Neurodevelopmental Disorders and Shared
      Medical Comorbidities - Relations that Translate from Bench to Bedside.
AB  - [This corrects the article on p. 142 in vol. 7, PMID: 27597832.].

PMID- 27703435
TI  - Ecological Momentary Assessment and Smartphone Application Intervention in
      Adolescents with Substance Use and Comorbid Severe Psychiatric Disorders: Study
      Protocol.
AB  - CONTEXT: Substance use disorders (SUDs) are highly prevalent among inpatient
      adolescents with psychiatric disorders. In this population, substance use and
      other psychiatric outcomes can reinforce one another. Despite the need for
      integrated interventions in youths with dual diagnoses, few specific instruments
      are available. App-based technologies have shown promising results to help reduce
      substance use in adolescents, but their applicability in youths with associated
      severe psychiatric disorders is poorly documented. We aim to evaluate the
      feasibility of an ecological momentary assessment (EMA) intervention for all
      substance users, and of a smartphone application for cannabis users (Stop
      Cannabis), for outpatient treatment after hospital discharge. METHODS AND
      ANALYSIS: All inpatient adolescents with psychiatric disorders hospitalized
      between 2016 and 2018 in a university hospital will be systematically screened
      for SUD and, if positive, will be assessed by an independent specialist addiction
      team. Participants with confirmed SUDs will be invited and helped to download an
      EMA app and, if required, the Stop-Cannabis app, the week preceding hospital
      discharge. Information about the acceptability and use of both apps and the
      validity of EMA data in comparison to clinical assessments will be assessed after
      6 months and 1 year. DISCUSSION: This research has been designed to raise
      specific issues for consideration regarding the sequence between substance use,
      contextual factors, and other psychiatric symptoms among adolescents with
      comorbid severe psychiatric disorders. A better understanding of the mechanisms
      involved will inform the development of integrated treatment for dual disorders
      at that age. ETHICS AND DISSEMINATION: The study has already been approved and
      granted. Dissemination will include presentations at international congresses as
      well as publications in peer-reviewed journals. TRIAL REGISTRATION: European
      Clinical Trials Database: Number 2016-001999-30.

PMID- 27703437
TI  - Verbal Ability, Argument Order, and Attitude Formation.
AB  - The current study explored the interaction of verbal ability and presentation
      order on readers' attitude formation when presented with two-sided arguments.
      Participants read arguments for and against compulsory voting and genetic
      engineering, and attitudes were assessed before and after reading the passages.
      Participants' verbal ability was measured, combining vocabulary knowledge and
      reading comprehension skill. Results suggested that low verbal-ability
      participants were more persuaded by the most recent set of arguments whereas high
      verbal-ability participants formed attitudes independent of presentation order.
      Contrary to previous literature, individual differences in the personality trait
      need for cognition did not interact with presentation order. The results suggest
      that verbal ability is an important moderator of the effect of presentation order
      when formulating opinions from complex prose.

PMID- 27703434
TI  - A Pilot Study of Mindfulness-Based Exposure Therapy in OEF/OIF Combat Veterans
      with PTSD: Altered Medial Frontal Cortex and Amygdala Responses in Social
      Emotional Processing.
AB  - Combat-related posttraumatic stress disorder (PTSD) is common among returning
      veterans, and is a serious and debilitating disorder. While highly effective
      treatments involving trauma exposure exist, difficulties with engagement and
      early drop may lead to sub-optimal outcomes. Mindfulness training may provide a
      method for increasing emotional regulation skills that may improve engagement in
      trauma-focused therapy. Here, we examine potential neural correlates of
      mindfulness training and in vivo exposure (non-trauma focused) using a novel
      group therapy [mindfulness-based exposure therapy (MBET)] in Afghanistan (OEF) or
      Iraq (OIF) combat veterans with PTSD. OEF/OIF combat veterans with PTSD (N = 23)
      were treated with MBET (N = 14) or a comparison group therapy [Present-centered
      group therapy (PCGT), N = 9]. PTSD symptoms were assessed at pre- and post
      therapy with Clinician Administered PTSD scale. Functional neuroimaging (3-T
      fMRI) before and after therapy examined responses to emotional faces (angry,
      fearful, and neutral faces). Patients treated with MBET had reduced PTSD symptoms
      (effect size d = 0.92) but effect was not significantly different from PCGT (d =
      0.43). Improvement in PTSD symptoms from pre- to post-treatment in both treatment
      groups was correlated with increased activity in rostral anterior cingulate
      cortex, dorsal medial prefrontal cortex (mPFC), and left amygdala. The MBET group
      showed greater increases in amygdala and fusiform gyrus responses to Angry faces,
      as well as increased response in left mPFC to Fearful faces. These preliminary
      findings provide intriguing evidence that MBET group therapy for PTSD may lead to
      changes in neural processing of social-emotional threat related to symptom
      reduction.

PMID- 27703438
TI  - Playing with Expectations: A Contextual View of Humor Development.
AB  - In the developmental literature, the idea has been proposed that young children
      do not understand the specificity of non-literal communicative acts. In this
      article, I focus on young children's ability to produce and understand different
      forms of humor. I explore the acquisition of the communicative contexts that
      enable children to engage in humorous interactions before they possess the
      capacity to analyze them in the terms afforded by a full-fledged theory of mind.
      I suggest that different forms of humor share several basic features and that we
      can construct a continuum from simple to sophisticated forms. In particular, I
      focus on teasing, a form of humor already present in preverbal infants that is
      also considered a typical feature of irony. I argue that all forms of humor can
      be regarded as a type of interaction that I propose to call "playing with
      expectations."

PMID- 27703439
TI  - The Role of Intuition in the Generation and Evaluation Stages of Creativity.
AB  - Both intuition and creativity are associated with knowledge creation, yet a clear
      link between them has not been adequately established. First, the available
      empirical evidence for an underlying relationship between intuition and
      creativity is sparse in nature. Further, this evidence is arguable as the
      concepts are diversely operationalized and the measures adopted are often not
      validated sufficiently. Combined, these issues make the findings from various
      studies examining the link between intuition and creativity difficult to
      replicate. Nevertheless, the role of intuition in creativity should not be
      neglected as it is often reported to be a core component of the idea generation
      process, which in conjunction with idea evaluation are crucial phases of creative
      cognition. We review the prior research findings in respect of idea generation
      and idea evaluation from the view that intuition can be construed as the gradual
      accumulation of cues to coherence. Thus, we summarize the literature on what role
      intuitive processes play in the main stages of the creative problem-solving
      process and outline a conceptual framework of the interaction between intuition
      and creativity. Finally, we discuss the main challenges of measuring intuition as
      well as possible directions for future research.

PMID- 27703440
TI  - Anodal Stimulation of the Left DLPFC Increases IGT Scores and Decreases Delay
      Discounting Rate in Healthy Males.
AB  - Previous correlational imaging studies have implicated the dorsolateral
      prefrontal cortex (DLPFC) in decision making. Using High-Definition Transcranial
      Direct Current Stimulation (HD-tDCS), the present study directly investigated the
      causal role of the DLPFC in performing the Iowa Gambling Task (IGT) and the Inter
      Temporal Choice (ITC) task. Three experiments were conducted: Experiment 1 (N =
      41) to study the left DLPFC, Experiment 2 (N = 49) to study the right DLPFC, and
      Experiment 3 (N = 20, a subset of those in Experiment 1) to switch the
      experimental and control conditions. All participants were healthy male college
      students. For Experiments 1 and 2, participants were randomly assigned to either
      the HD-tDCS or the sham stimulation condition. For Experiment 3, participants
      were assigned to the condition they were not in during Experiment 1. Results
      showed that HD-tDCS over the left DLPFC increased IGT score, decreased the
      recency parameter in IGT, and lowered delay discounting rate (k) in the ITC task.
      We discussed the potential roles of impulse control and time perception in
      mediating the effect of tDCS stimulation of left DLPFC on decision making. Our
      results have clinical implications for the treatment of disorders involving poor
      decision-making, such as addictions.

PMID- 27703441
TI  - Rational Emotive Behavior Therapy (REBT), Irrational and Rational Beliefs, and
      the Mental Health of Athletes.
AB  - In this article Rational Emotive Behavior Therapy (REBT) is proposed as a
      potentially important framework for the understanding and promotion of mental
      health in athletes. Cognitive-behavioral approaches predominate in the provision
      of sport psychology, and often form the backbone of psychological skills training
      for performance enhancement and maintenance. But far from being solely
      performance-focused, the cognitive-behavioral approach to sport psychology can
      restore, promote, and maintain mental health. This review article presents REBT
      (Ellis, 1957), the original cognitive behavioral therapy, as a valuable approach
      to addressing mental health issues in sport. REBT holds that it is not events
      that directly cause emotions and behaviors. Rather, it is one's beliefs about the
      events that lead to emotional and behavioral reactivity. Further, REBT
      distinguishes between rational and irrational beliefs, and suggests that in
      response to failure, maltreatment, and misfortune, people can react with either
      healthy or unhealthy emotional and behavioral responses. The extant research
      indicates that irrational beliefs lead to unhealthy negative emotions, a range of
      pathological conditions, and a host of maladaptive behaviors that undermine
      mental health. Therefore, REBT proposes a process for the reduction of irrational
      beliefs and the promotion of rational beliefs. The use of REBT in sport is seldom
      reported in literature, but research is growing. This review article proposes
      three important areas of investigation that will aid the understanding of
      irrational beliefs and the application of REBT within sport. These areas are: (1)
      the influence of irrational beliefs and REBT on the mental health of athletes,
      (2) the influence of irrational beliefs and REBT on athletic performance, (3) the
      origins and development of irrational beliefs in athletes. Each area is discussed
      in turn, offering a critical and progressive review of the literature as well as
      highlighting research deficits, and recommendations to address each of the three
      areas of investigation.

PMID- 27703442
TI  - Corrigendum: Uncovering phenotypes of poor-pitch singing: the Sung Performance
      Battery (SPB).
AB  - [This corrects the article on p. 714 in vol. 4, PMID: 24151475.].

PMID- 27703443
TI  - A Cross-sectional Survey and Cross-sectional Clinical Trial to Determine the
      Prevalence and Management of Eye Movement Disorders and Vestibular Dysfunction in
      Post-Stroke Patients in the Sub-Acute Phase: Protocol.
AB  - INTRODUCTION: Visual impairment, specifically eye movement disorders and
      vestibular dysfunction may have a negative influence on the functional recovery
      in post-stroke patients. This type of sensory dysfunction may further be
      associated with poor functional outcome in patients' post-stroke. METHODS: In
      phase 1, a cross-sectional survey (n = 100) will be conducted to determine the
      prevalence of eye movement disorders and vestibular dysfunction in patients who
      sustained a stroke. A cross-sectional clinical trial (n = 60) will be conducted
      during phase 2 of the study to determine the effect of the combination of
      vestibular rehabilitation therapy (VRT) and visual scanning exercises (VSE)
      (experimental group) integrated with task-specific activities compared with the
      effect of task-specific activities as an intervention (control group) on patients
      who present with eye movement impairment and central vestibular dysfunction post
      stroke. An audiologist will assess (a) visual acuity (static and dynamic), (b)
      nystagmus, (c) saccadic eye movements, (d) smooth pursuit eye movements, (e)
      vestibulo-ocular reflex, and (f) saccular, utricular, and vestibular nerve
      function. An independent physiotherapist will assess (1) cognitive function, (2)
      residual oculomotor visual performance, (3) visual-perceptual system, (4)
      functional balance, (5) gait, (6) functional ability, (7) presence of anxiety
      and/or depression, and (8) level of participation in physical activity. ETHICS
      AND DISSEMINATION: Ethics approval has been obtained from the Ethics Committee of
      the Faculty of Health Sciences at the University of Pretoria (UP) (374/2015). The
      study will be submitted as fulfillment for the PhD degree at UP. Dissemination
      will include submission to peer-reviewed professional journals and presentation
      at congresses. Training of rehabilitation team members on the integration of VSE
      and VRT into task-specific activities in rehabilitation will be done if the
      outcome of the experimental group's functional performance is clinically and
      statistically significantly better than the control group on the Barthel Index.
      TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR201509001223262).

PMID- 27703444
TI  - Prevalence of Brain MRI Markers of Hemorrhagic Risk in Patients with Stroke and
      Atrial Fibrillation.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs), cortical superficial
      siderosis, white matter lesions (WML), and cerebral atrophy may signify greater
      bleeding risk particularly in patients in whom anticoagulation is to be
      considered. We investigated their prevalence and associations with stroke type in
      patients with stroke and atrial fibrillation (AF). MATERIALS AND METHODS: Cross
      sectional sample, Monash Medical Centre (Melbourne, Australia) between 2010 and
      2013, with brain MRI. MRI abnormalities were rated using standardized methods.
      Logistic regression was used to study associations adjusting for age and sex.
      RESULTS: There were 170 patients, mean age 78 years (SD 9.8), 154 (90.6%) with
      ischemic stroke. Prevalence of MRI markers were any microbleed 49%, multiple
      (>=2) microbleeds 30%, confluent WMLs 18.8%, siderosis 8.9%, severe cerebral
      atrophy 37.7%. Combinations of the severe manifestations of these markers were
      much less prevalent (2.9-12.4%). Compared with ischemic stroke, those with
      hemorrhagic stroke were more likely to have >=10 microbleeds (OR 5.50 95% CI 1.46
      20.77, p = 0.012) and siderosis (OR 6.24, 95% CI 1.74-22.40, p = 0.005).
      Siderosis was associated with multiple microbleeds (OR 8.14, 95% CI 2.38-27.86, p
      = 0.001). Patients admitted with hemorrhagic stroke and multiple microbleeds were
      more frequently anticoagulated prior to stroke (6/7, 85.7%) than in those with
      single (1/2, 50%) or no microbleeds (4/7, 57%). CONCLUSION: Multiple CMBs, severe
      WML, and severe cerebral atrophy were common individually in hospitalized
      patients with stroke and AF, but less so in combination. A higher burden of CMBs
      may be associated with intracerebral hemorrhage in stroke patients with AF.

PMID- 27703445
TI  - Asking New Questions with Old Data: The Centralized Open-Access Rehabilitation
      Database for Stroke.
AB  - BACKGROUND: This paper introduces a tool for streamlining data integration in
      rehabilitation science, the Centralized Open-Access Rehabilitation database for
      Stroke (SCOAR), which allows researchers to quickly visualize relationships among
      variables, efficiently share data, generate hypotheses, and enhance clinical
      trial design. METHODS: Bibliographic databases were searched according to
      inclusion criteria leaving 2,892 titles that were further screened to 514
      manuscripts to be screened by full text, leaving 215 randomized controlled trials
      (RCTs) in the database (489 independent groups representing 12,847 patients).
      Demographic, methodological, and statistical data were extracted by independent
      coders and entered into SCOAR. RESULTS: Trial data came from 114 locations in 27
      different countries and represented patients with a wide range of ages, 62 year
      [41; 85] [shown as median (range)] and at various stages of recovery following
      their stroke, 141 days [1; 3372]. There was considerable variation in the dose of
      therapy that patients received, 20 h [0; 221], over interventions of different
      durations, 28 days [10; 365]. There was also a lack of common data elements
      (CDEs) across trials, but this lack of CDEs was most pronounced for baseline
      assessments of patient impairment and severity of stroke. CONCLUSION: Data
      integration across hundreds of RCTs allows clinicians and researchers to quickly
      visualize data from the history of the field and lays the foundation for making
      SCOAR a living database to which researchers can upload new data as trial results
      are published. SCOAR is a useful tool for clinicians and researchers that will
      facilitate data visualization, data sharing, the finding of relevant past
      studies, and the design of clinical trials by enabling more accurate and
      comprehensive power analyses. Furthermore, these data speak to the need for CDEs
      specific to stroke rehabilitation in randomized controlled trials. PROSPERO 2014:
      CRD42014009010.

PMID- 27703446
TI  - A Novel Germline Mutation of KEAP1 (R483H) Associated with a Non-Toxic
      Multinodular Goiter.
AB  - BACKGROUND: A germline mutation of KEAP1 gene was reported as a novel genetic
      abnormality associated with familial multinodular goiter. That report was
      limited, and the pathogenic features were not well established. PATIENT FINDINGS:
      We report a 47-year-old Japanese woman who presented with hyperthyroidism and a
      large multinodular goiter. The family history was notable for a paternal history
      of goiter. Graves' disease was diagnosed based on positive TRAb, but scintiscan
      imaging showed that the patient's radioiodine uptake was restricted in the non
      nodular areas, indicating largely cold nodules. A total thyroidectomy was
      performed. The resected thyroid tissue weighed 209 g, and subsequent pathological
      findings were benign. The patient had a germline heterozygous KEAP1 mutation, c.
      1448 G > A, resulting in an amino acid substitution (p.R483H). A next-generation
      sequencing analysis covering all known genes associated with multinodular goiter
      showed no additional germline mutation. The nuclear accumulation of NRF2, a
      protein associated with KEAP1, was shown at much higher rates in the patient's
      nodules compared with nodules obtained from four unrelated patients with
      multinodular goiters. CONCLUSION: A novel germline mutation (R483H) of KEAP1 gene
      was associated with the development of a non-toxic multinodular goiter.

PMID- 27703447
TI  - Autophagy Is Associated with Pathogenesis of Haemophilus parasuis.
AB  - Haemophilus parasuis (H. parasuis) is a common commensal Gram-negative
      extracellular bacterium in the upper respiratory tract of swine, which can cause
      Glasser's disease in stress conditions. Research on the pathogenicity of H.
      parasuis has mainly focused on immune evasion and bacterial virulence factors,
      while few studies have examined the interactions of H. parasuis and its host.
      Autophagy is associated with the replication and proliferation of many pathogenic
      bacteria, but whether it plays a role during infection by H. parasuis is unknown.
      In this study, an adenovirus construct expressing GFP, RFP, and LC3 was used to
      infect H. parasuis. Western blotting, laser confocal microscopy, and electron
      microscopy showed that Hps5 infection induced obvious autophagy in PK-15 cells.
      In cells infected with strains of H. parasuis differing in invasiveness, the
      levels of autophagy were positively correlated with the presence of alive
      bacteria in PK-15 cells. In addition, autophagy inhibited the invasion of Hps5 in
      PK-15 cells. Autophagy related genes Beclin, Atg5 and Atg7 were silenced with RNA
      interference, the results showed that autophagy induced by H. parasuis infection
      is a classical pathway. Our observations demonstrate that H. parasuis can induce
      autophagy and that the levels of autophagy are associated with the presence of
      alive bacteria in cells, which opened novel avenues to further our understanding
      of H. parasuis-host interplay and pathogenesis.

PMID- 27703448
TI  - Oxygen Tension and Riboflavin Gradients Cooperatively Regulate the Migration of
      Shewanella oneidensis MR-1 Revealed by a Hydrogel-Based Microfluidic Device.
AB  - Shewanella oneidensis is a model bacterial strain for studies of
      bioelectrochemical systems (BESs). It has two extracellular electron transfer
      pathways: (1) shuttling electrons via an excreted mediator riboflavin; and (2)
      direct contact between the c-type cytochromes at the cell membrane and the
      electrode. Despite the extensive use of S. oneidensis in BESs such as microbial
      fuel cells and biosensors, many basic microbiology questions about S. oneidensis
      in the context of BES remain unanswered. Here, we present studies of motility and
      chemotaxis of S. oneidensis under well controlled concentration gradients of two
      electron acceptors, oxygen and oxidized form of riboflavin (flavin+), using a
      newly developed microfluidic platform. Experimental results demonstrate that
      either oxygen or flavin+ is a chemoattractant to S. oneidensis. The chemotactic
      tendency of S. oneidensis in a flavin+ concentration gradient is significantly
      enhanced in an anaerobic in contrast to an aerobic condition. Furthermore, either
      a low oxygen tension or a high flavin+ concentration considerably enhances the
      speed of S. oneidensis. This work presents a robust microfluidic platform for
      generating oxygen and/or flavin+ gradients in an aqueous environment, and
      demonstrates that two important electron acceptors, oxygen and oxidized
      riboflavin, cooperatively regulate S. oneidensis migration patterns. The
      microfluidic tools presented as well as the knowledge gained in this work can be
      used to guide the future design of BESs for efficient electron production.

PMID- 27703449
TI  - Exploratory Investigation of Bacteroides fragilis Transcriptional Response during
      In vitro Exposure to Subinhibitory Concentration of Metronidazole.
AB  - Bacteroides fragilis, member from commensal gut microbiota, is an important
      pathogen associated to endogenous infections and metronidazole remains a valuable
      antibiotic for the treatment of these infections, although bacterial resistance
      is widely reported. Considering the need of a better understanding on the global
      mechanisms by which B. fragilis survive upon metronidazole exposure, we performed
      a RNA-seq transcriptomic approach with validation of gene expression results by
      qPCR. Bacteria strains were selected after in vitro subcultures with
      subinhibitory concentration (SIC) of the drug. From a wild type B. fragilis ATCC
      43859 four derivative strains were selected: first and fourth subcultures under
      metronidazole exposure and first and fourth subcultures after drug removal.
      According to global gene expression analysis, 2,146 protein coding genes were
      identified, of which a total of 1,618 (77%) were assigned to a Gene Ontology term
      (GO), indicating that most known cellular functions were taken. Among these 2,146
      protein coding genes, 377 were shared among all strains, suggesting that they are
      critical for B. fragilis survival. In order to identify distinct expression
      patterns, we also performed a K-means clustering analysis set to 15 groups. This
      analysis allowed us to detect the major activated or repressed genes encoding for
      enzymes which act in several metabolic pathways involved in metronidazole
      response such as drug activation, defense mechanisms against superoxide ions,
      high expression level of multidrug efflux pumps, and DNA repair. The strains
      collected after metronidazole removal were functionally more similar to those
      cultured under drug pressure, reinforcing that drug-exposure lead to drastic
      persistent changes in the B. fragilis gene expression patterns. These results may
      help to elucidate B. fragilis response during metronidazole exposure, mainly at
      SIC, contributing with information about bacterial survival strategies under
      stress conditions in their environment.

PMID- 27703450
TI  - First Report of Vibrio tubiashii Associated with a Massive Larval Mortality Event
      in a Commercial Hatchery of Scallop Argopecten purpuratus in Chile.
AB  - The VPAP30 strain was isolated as the highly predominant bacteria from an episode
      of massive larval mortality occurring in a commercial culture of the Chilean
      scallop Argopecten purpuratus. The main aims of this study were, to characterize
      and identify the pathogenic strain using biochemical and molecular methods to
      demonstrate its pathogenic activity on scallop larvae, to characterize its
      pathogenic properties and to describe the chronology of this pathology. The
      pathogenic strain was identified as Vibrio tubiashii based on its phenotypic
      properties and the sequence analysis of its 16S rRNA and housekeeping genes
      (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA and topA). When triplicate cultures of
      healthy 10-day-old scallop larvae were challenged with 1 * 105 colony forming
      units (CFU) mL-1 of the VPAP30 strain, percentages of larval survival of 78.87 +/
      3.33%, 34.32 +/- 4.94%, and 0% were observed at 12, 24, and 36 h, respectively;
      whereas uninfected larval cultures showed survival rates of 97.4 +/- 1.24% after
      of 48 h. Clinical symptoms exhibited by the scallop larvae infected with the
      VPAP30 strain include the accumulation of bacteria around the scallop larvae,
      velum disruption and necrosis of digestive gland. The 50% lethal dose (LD50) of
      VPAP30 strain at 24 and 48 h was 1.3 * 104 and 1.2 * 103 CFU mL-1, respectively.
      The invasive pathogenic activity of the VPAP30 strain was investigated with
      staining of the bacterial pathogen with 5-DTAF and analyzing bacterial invasion
      using epifluorescence, and a complete bacterial dissemination inside the larvae
      at 24 h post-infection was observed. When scallop larvae were inoculated with
      cell-free extracellular products (ECPs) of VPAP30, the larval survival rate was
      59.5 +/- 1.66%, significantly (P < 0.001) lower than the control group (97.4 +/-
      1.20%) whereas larvae treated with heat-treated ECPs exhibited a survival rate of
      61.6 +/- 1.84% after 48 h of exposure. This is the first report of the isolation
      of V. tubiashii from the diseased larvae of the scallop A. purpuratus, occurring
      in a commercial culture in Chile, and it was demonstrated that the VPAP30 strain
      exhibits high pathogenic activity on scallop larvae, mediated both by bacterial
      invasion and the production of toxigenic heat-stable compounds.

PMID- 27703451
TI  - Comparative Transcriptomic Analysis Reveals Novel Insights into the Adaptive
      Response of Skeletonema costatum to Changing Ambient Phosphorus.
AB  - Phosphorus (P) is a limiting macronutrient for diatom growth and productivity in
      the ocean. Much effort has been devoted to the physiological response of marine
      diatoms to ambient P change, however, the whole-genome molecular mechanisms are
      poorly understood. Here, we utilized RNA-Seq to compare the global gene
      expression patterns of a marine diatom Skeletonema costatum grown in inorganic P
      replete, P-deficient, and inorganic- and organic-P resupplied conditions. In
      total 34,942 unique genes were assembled and 20.8% of them altered significantly
      in abundance under different P conditions. Genes encoding key enzymes/proteins
      involved in P utilization, nucleotide metabolism, photosynthesis, glycolysis, and
      cell cycle regulation were significantly up-regulated in P-deficient cells. Genes
      participating in circadian rhythm regulation, such as circadian clock associated
      1, were also up-regulated in P-deficient cells. The response of S. costatum to
      ambient P deficiency shows several similarities to the well-described responses
      of other marine diatom species, but also has its unique features. S. costatum has
      evolved the ability to re-program its circadian clock and intracellular
      biological processes in response to ambient P deficiency. This study provides new
      insights into the adaptive mechanisms to ambient P deficiency in marine diatoms.

PMID- 27703452
TI  - Anti-rheumatoid Activity of Secondary Metabolites Produced by Endophytic
      Chaetomium globosum.
AB  - The aim of the present study was to investigate the anti-rheumatoid activity of
      secondary metabolites produced by endophytic mycobiota in Egypt. A total of 27
      endophytic fungi were isolated from 10 dominant medicinal plant host species in
      Wadi Tala, Saint Katherine Protectorate, arid Sinai, Egypt. Of those taxa, seven
      isolates of Chaetomium globosum (CG1-CG7), being the most frequent taxon, were
      recovered from seven different host plants and screened for production of active
      anti-inflammatory metabolites. Isolates were cultivated on half - strength potato
      dextrose broth for 21 days at 28 degrees C on a rotatory shaker at 180 rpm, and
      extracted in ethyl acetate and methanol, respectively. The probable inhibitory
      effects of both extracts against an adjuvant induced arthritis (AIA) rat model
      were examined and compared with the effects of methotrexate (MTX) as a standard
      disease-modifying anti-rheumatoid drug. Disease activity and mobility scoring of
      AIA, histopathology and transmission electron microscopy (TEM) were used to
      evaluate probable inhibitory roles. A significant reduction (P < 0.05) in the
      severity of arthritis was observed in both the methanolic extract of CG6 (MCG6)
      and MTX treatment groups 6 days after treatment commenced. The average arthritis
      score of the MCG6 treatment group was (10.7 +/- 0.82) compared to (13.8 +/- 0.98)
      in the positive control group. The mobility score of the MCG6 treatment group
      (1.50 +/- 0.55) was significantly lower than that of the positive control group
      (3.33 +/- 0.82). In contrast, the ethyl acetate extract of CG6 (EACG6) treatment
      group showed no improvements in arthritis and mobility scores in AIA model rats.
      Histopathology and TEM findings confirmed the observation. Isolate CG6 was
      subjected to sequencing for confirmation of phenotypic identification. The
      internal transcribed spacer (ITS) 1-5.8 s - ITS2 rDNA sequences obtained were
      compared with those deposited in the GenBank Database and registered with
      accession number KC811080 in the NCBI Database. The present study revealed that
      the methanol extract of endophytic fungus C. globosum (KC811080) recovered from
      maidenhair fern has an inhibitory effect on inflammation, histopathology and
      morphological features of rheumatoid arthritis in an AIA rat model.

PMID- 27703453
TI  - Evaluation of the Microbial Diversity in Amyotrophic Lateral Sclerosis Using High
      Throughput Sequencing.
AB  - More and more evidences indicate that diseases of the central nervous system have
      been seriously affected by fecal microbes. However, little work is done to
      explore interaction between amyotrophic lateral sclerosis (ALS) and fecal
      microbes. In the present study, high-throughput sequencing method was used to
      compare the intestinal microbial diversity of healthy people and ALS patients.
      The principal coordinate analysis, Venn and unweighted pair-group method using
      arithmetic averages (UPGMA) showed an obvious microbial changes between healthy
      people (group H) and ALS patients (group A), and the average ratios of
      Bacteroides, Faecalibacterium, Anaerostipes, Prevotella, Escherichia, and
      Lachnospira at genus level between ALS patients and healthy people were 0.78,
      2.18, 3.41, 0.35, 0.79, and 13.07. Furthermore, the decreased
      Firmicutes/Bacteroidetes ratio at phylum level using LEfSE (LDA > 4.0), together
      with the significant increased genus Dorea (harmful microorganisms) and
      significant reduced genus Oscillibacter, Anaerostipes, Lachnospiraceae
      (beneficial microorganisms) in ALS patients, indicated that the imbalance in
      intestinal microflora constitution had a strong association with the pathogenesis
      of ALS.

PMID- 27703454
TI  - Exome Sequencing Reveals Primary Immunodeficiencies in Children with Community
      Acquired Pseudomonas aeruginosa Sepsis.
AB  - One out of three pediatric sepsis deaths in high income countries occur in
      previously healthy children. Primary immunodeficiencies (PIDs) have been
      postulated to underlie fulminant sepsis, but this concept remains to be confirmed
      in clinical practice. Pseudomonas aeruginosa (P. aeruginosa) is a common
      bacterium mostly associated with health care-related infections in
      immunocompromised individuals. However, in rare cases, it can cause sepsis in
      previously healthy children. We used exome sequencing and bioinformatic analysis
      to systematically search for genetic factors underpinning severe P. aeruginosa
      infection in the pediatric population. We collected blood samples from 11
      previously healthy children, with no family history of immunodeficiency, who
      presented with severe sepsis due to community-acquired P. aeruginosa bacteremia.
      Genomic DNA was extracted from blood or tissue samples obtained intravitam or
      postmortem. We obtained high-coverage exome sequencing data and searched for rare
      loss-of-function variants. After rigorous filtrations, 12 potentially causal
      variants were identified. Two out of eight (25%) fatal cases were found to carry
      novel pathogenic variants in PID genes, including BTK and DNMT3B. This study
      demonstrates that exome sequencing allows to identify rare, deleterious human
      genetic variants responsible for fulminant sepsis in apparently healthy children.
      Diagnosing PIDs in such patients is of high relevance to survivors and affected
      families. We propose that unusually severe and fatal sepsis cases in previously
      healthy children should be considered for exome/genome sequencing to search for
      underlying PIDs.

PMID- 27703455
TI  - Modulation of Phenotype and Function of Human CD4+CD25+ T Regulatory Lymphocytes
      Mediated by cAMP-Elevating Agents.
AB  - We have shown that cholera toxin (CT) and other cyclic AMP (cAMP)-elevating
      agents induce upregulation of the inhibitory molecule CTLA-4 in human resting
      CD4+ T lymphocytes, which following the treatment acquired suppressive functions.
      In this study, we evaluated the effect of cAMP-elevating agents on human
      CD4+CD25+ T cells, which include the T regulatory cells (Tregs) that play a
      pivotal role in the maintenance of immunological tolerance. We found that cAMP
      elevating agents induce upregulation of CTLA-4 in CD4+CD25- and further enhance
      its expression in CD4+CD25+ T cells. We observed an increase of two isoforms of
      mRNA coding for the membrane and the soluble CTLA-4 molecules, suggesting that
      the regulation of CTLA-4 expression by cAMP is at the transcriptional level. In
      addition, we found that the increase of cAMP in CD4+CD25+ T cells converts the
      CD4+CD25+Foxp3- T cells in CD4+CD25+Foxp3+ T cells, whereas the increase of cAMP
      in CD4+CD25- T cells did not upregulate Foxp3 in the absence of activation
      stimuli. To investigate the function of these cells, we performed an in vitro
      suppression assay by culturing CD4+CD25+ T cells untreated or pre-treated with CT
      with anti-CD3 mAbs-stimulated autologous peripheral blood mononuclear cell. We
      found that CT enhances the inhibitory function of CD4+CD25+ T cells, CD4+, and
      CD8+ T cell proliferation and IFNgamma production are strongly inhibited by
      CD4+CD25+ T cells pre-treated with cAMP-elevating agents. Furthermore, we found
      that CD4+CD25+ T lymphocytes pre-treated with cAMP-elevating agents induce the
      upregulation of CD80 and CD86 co-stimulatory molecules on immature dendritic
      cells (DCs) in the absence of antigenic stimulation, however without leading to
      full DC maturation. These data show that the increase of intracellular cAMP
      modulates the phenotype and function of human CD4+CD25+ T cells.

PMID- 27703458
TI  - DRI-Grass: A New Experimental Platform for Addressing Grassland Ecosystem
      Responses to Future Precipitation Scenarios in South-East Australia.
AB  - Climate models predict shifts in the amount, frequency and seasonality of
      rainfall. Given close links between grassland productivity and rainfall, such
      changes are likely to have profound effects on the functioning of grassland
      ecosystems and modify species interactions. Here, we introduce a unique, new
      experimental platform - DRI-Grass (Drought and Root Herbivore Interactions in a
      Grassland) - that exposes a south-eastern Australian grassland to five rainfall
      regimes [Ambient (AMB), increased amount (IA, +50%), reduced amount (RA, -50%),
      reduced frequency (RF, single rainfall event every 21 days, with total amount
      unchanged) and summer drought (SD, 12-14 weeks without water, December-March)],
      and contrasting levels of root herbivory. Incorporation of a belowground
      herbivore (root-feeding scarabs) addition treatment allows novel investigation of
      ecological responses to the twin stresses of altered rainfall and root herbivory.
      We quantified effects of permanently installed rain shelters on microclimate by
      comparison with outside plots, identifying small shelter effects on air
      temperature (-0.19 degrees C day, +0.26 degrees C night), soil water content
      (SWC; -8%) and photosynthetically active radiation (PAR; -16%). Shelters were
      associated with modest increases in net primary productivity (NPP), particularly
      during the cool season. Rainfall treatments generated substantial differences in
      SWC, with the exception of IA; the latter is likely due to a combination of
      higher transpiration rates associated with greater plant biomass in IA and the
      low water-holding capacity of the well-drained, sandy soil. Growing season NPP
      was strongly reduced by SD, but did not respond to the other rainfall treatments.
      Addition of root herbivores did not affect plant biomass and there were no
      interactions between herbivory and rainfall treatments in the 1st year of study.
      Root herbivory did, however, induce foliar silicon-based defenses in Cynodon
      dactylon and Eragrostis curvula. Rapid recovery of NPP following resumption of
      watering in SD plots indicates high functional resilience at the site, and may
      reflect adaptation of the vegetation to historically high variability in
      rainfall, both within- and between years. DRI-Grass provides a unique platform
      for understanding how ecological interactions will be affected by changing
      rainfall regimes and, specifically, how belowground herbivory modifies grassland
      resistance and resilience to climate extremes.

PMID- 27703456
TI  - Cancers Related to Immunodeficiencies: Update and Perspectives.
AB  - The life span of patients with primary and secondary immunodeficiency is
      increasing due to recent improvements in therapeutic strategies. While the
      incidence of primary immunodeficiencies (PIDs) is 1:10,000 births, that of
      secondary immunodeficiencies are more common and are associated with
      posttransplantation immune dysfunction, with immunosuppressive medication for
      human immunodeficiency virus or with human T-cell lymphotropic virus infection.
      After infection, malignancy is the most prevalent cause of death in both children
      and adults with (PIDs). PIDs more often associated with cancer include common
      variable immunodeficiency (CVID), Wiskott-Aldrich syndrome, ataxia
      telangiectasia, and severe combined immunodeficiency. This suggests that a
      protective immune response against both infectious non-self-(pathogens) and
      malignant self-challenges (cancer) exists. The increased incidence of cancer has
      been attributed to defective elimination of altered or "transformed" cells and/or
      defective immunity towards cancer cells. The concept of aberrant immune
      surveillance occurring in PIDs is supported by evidence in mice and from patients
      undergoing immunosuppression after transplantation. Here, we discuss the
      importance of PID defects in the development of malignancies and the current
      limitations associated with molecular pathogenesis of these diseases and
      emphasize the need for further knowledge of how specific mutations can modulate
      the immune system to alter immunosurveillance and thereby play a key role in the
      etiology of malignancies in PID patients.

PMID- 27703457
TI  - Nod2: A Critical Regulator of Ileal Microbiota and Crohn's Disease.
AB  - The human intestinal tract harbors large bacterial community consisting of
      commensal, symbiotic, and pathogenic strains, which are constantly interacting
      with the intestinal immune system. This interaction elicits a non-pathological
      basal level of immune responses and contributes to shaping both the intestinal
      immune system and bacterial community. Recent studies on human microbiota are
      revealing the critical role of intestinal bacterial community in the pathogenesis
      of both systemic and intestinal diseases, including Crohn's disease (CD). NOD2
      plays a key role in the regulation of microbiota in the small intestine. NOD2 is
      highly expressed in ileal Paneth cells that provide critical mechanism for the
      regulation of ileal microbiota through the secretion of anti-bacterial compounds.
      Genome mapping of CD patients revealed that loss of function mutations in NOD2
      are associated with ileal CD. Genome-wide association studies further
      demonstrated that NOD2 is one of the most critical genetic factor linked to ileal
      CD. The bacterial community in the ileum is indeed dysregulated in Nod2-deficient
      mice. Nod2-deficient ileal epithelia exhibit impaired ability of killing
      bacteria. Thus, altered interactions between ileal microbiota and mucosal
      immunity through NOD2 mutations play significant roles in the disease
      susceptibility and pathogenesis in CD patients, thereby depicting NOD2 as a
      critical regulator of ileal microbiota and CD.

PMID- 27703460
TI  - Combining Image Analysis, Genome Wide Association Studies and Different Field
      Trials to Reveal Stable Genetic Regions Related to Panicle Architecture and the
      Number of Spikelets per Panicle in Rice.
AB  - Number of spikelets per panicle (NSP) is a key trait to increase yield potential
      in rice (O. sativa). The architecture of the rice inflorescence which is mainly
      determined by the length and number of primary (PBL and PBN) and secondary (SBL
      and SBN) branches can influence NSP. Although several genes controlling panicle
      architecture and NSP in rice have been identified, there is little evidence of
      (i) the genetic control of panicle architecture and NSP in different environments
      and (ii) the presence of stable genetic associations with panicle architecture
      across environments. This study combines image phenotyping of 225 accessions
      belonging to a genetic diversity array of indica rice grown under irrigated field
      condition in two different environments and Genome Wide Association Studies
      (GWAS) based on the genotyping of the diversity panel, providing 83,374 SNPs.
      Accessions sown under direct seeding in one environement had reduced Panicle
      Length (PL), NSP, PBN, PBL, SBN, and SBL compared to those established under
      transplanting in the second environment. Across environments, NSP was
      significantly and positively correlated with PBN, SBN and PBL. However, the
      length of branches (PBL and SBL) was not significantly correlated with variables
      related to number of branches (PBN and SBN), suggesting independent genetic
      control. Twenty- three GWAS sites were detected with P <= 1.0E-04 and 27 GWAS
      sites with p <= 5.9E-04. We found 17 GWAS sites related to NSP, 10 for PBN and 11
      for SBN, 7 for PBL and 11 for SBL. This study revealed new regions related to
      NSP, but only three associations were related to both branching number (PBN and
      SBN) and NSP. Two GWAS sites associated with SBL and SBN were stable across
      contrasting environments and were not related to genes previously reported. The
      new regions reported in this study can help improving NSP in rice for both direct
      seeded and transplanted conditions. The integrated approach of high-throughput
      phenotyping, multi-environment field trials and GWAS has the potential to dissect
      complex traits, such as NSP, into less complex traits and to match single
      nucleotide polymorphisms with relevant function under different environments,
      offering a potential use for molecular breeding.

PMID- 27703459
TI  - Expansion and Functional Divergence of AP2 Group Genes in Spermatophytes
      Determined by Molecular Evolution and Arabidopsis Mutant Analysis.
AB  - The APETALA2 (AP2) genes represent the AP2 group within a large group of DNA
      binding proteins called AP2/EREBP. The AP2 gene is functional and necessary for
      flower development, stem cell maintenance, and seed development, whereas the
      other members of AP2 group redundantly affect flowering time. Here we study the
      phylogeny of AP2 group genes in spermatophytes. Spermatophyte AP2 group genes can
      be classified into AP2 and TOE types, six clades, and we found that the AP2 group
      homologs in gymnosperms belong to the AP2 type, whereas TOE types are absent,
      which indicates the AP2 type gene are more ancient and TOE type was split out of
      AP2 type and losing the major function. In Brassicaceae, the expansion of AP2 and
      TOE type lead to the gene number of AP2 group were up to six. Purifying selection
      appears to have been the primary driving force of spermatophyte AP2 group
      evolution, although positive selection occurred in the AP2 clade. The transition
      from exon to intron of AtAP2 in Arabidopsis mutant leads to the loss of gene
      function and the same situation was found in AtTOE2. Combining this evolutionary
      analysis and published research, the results suggest that typical AP2 group genes
      may first appear in gymnosperms and diverged in angiosperms, following expansion
      of group members and functional differentiation. In angiosperms, AP2 genes (AP2
      clade) inherited key functions from ancestors and other genes of AP2 group lost
      most function but just remained flowering time controlling in gene formation. In
      this study, the phylogenies of AP2 group genes in spermatophytes was analyzed,
      which supported the evidence for the research of gene functional evolution of AP2
      group.

PMID- 27703461
TI  - Genome-Wide Characterization of the MADS-Box Gene Family in Radish (Raphanus
      sativus L.) and Assessment of Its Roles in Flowering and Floral Organogenesis.
AB  - The MADS-box gene family is an important transcription factor (TF) family that is
      involved in various aspects of plant growth and development, especially flowering
      time and floral organogenesis. Although it has been reported in many plant
      species, the systematic identification and characterization of MADS-box TF family
      is still limited in radish (Raphanus sativus L.). In the present study, a
      comprehensive analysis of MADS-box genes was performed, and a total of 144 MADS
      box family members were identified from the whole radish genome. Meanwhile, a
      detailed list of MADS-box genes from other 28 plant species was also
      investigated. Through the phylogenetic analysis between radish and Arabidopsis
      thaliana, all the RsMADS genes were classified into two groups including 68 type
      I (31 Malpha, 12 Mbeta and 25Mgamma) and 76 type II (70 MIKCC and 6 MIKC*). Among
      them, 41 (28.47%) RsMADS genes were located in nine linkage groups of radish from
      R1 to R9. Moreover, the homologous MADS-box gene pairs were identified among
      radish, A. thaliana, Chinese cabbage and rice. Additionally, the expression
      profiles of RsMADS genes were systematically investigated in different tissues
      and growth stages. Furthermore, quantitative real-time PCR analysis was employed
      to validate expression patterns of some crucial RsMADS genes. These results could
      provide a valuable resource to explore the potential functions of RsMADS genes in
      radish, and facilitate dissecting MADS-box gene-mediated molecular mechanisms
      underlying flowering and floral organogenesis in root vegetable crops.

PMID- 27703462
TI  - The Rice Eukaryotic Translation Initiation Factor 3 Subunit e (OseIF3e)
      Influences Organ Size and Pollen Maturation.
AB  - Eukaryotic translation initiation factor 3 (eIF3) is a large protein complex that
      participates in most translation initiation processes. While eIF3 has been well
      characterized, less is known about the roles of individual eIF3 subunits,
      particularly in plants. Here, we identified and characterized OseIF3e in rice
      (Oryza sativa L.). OseIF3e was constitutively expressed in various tissues, but
      most strongly in vigorously growing organs. Transgenic OseIF3e-silenced rice
      plants showed inhibited growth in seedling and vegetative stages. Repression of
      OseIF3e led to defects in pollen maturation but did not affect pollen mitosis. In
      rice, eIF3e interacted with eIF3 subunits b, d, e, f, h, and k, and with eIF6,
      forming homo- and heterodimers to initiate translation. Furthermore, OseIF3e was
      shown by yeast two-hybrid assay to specifically bind to inhibitors of cyclin
      dependent kinases 1, 5, and 6. This interaction was mediated by the sequence of
      amino acid residues at positions 118-138, which included a conserved motif
      (IGPEQIETLYQFAKF). These results suggested although OseIF3e is not a "functional
      core" subunit of eIF3, it still plays crucial roles in rice growth and
      development, in combination with other factors. We proposed a pathway by which
      OseIF3e influence organ size and pollen maturation in rice, providing an
      opportunity to optimize plant architecture for crop breeding.

PMID- 27703463
TI  - Pectins, Endopolygalacturonases, and Bioenergy.
AB  - The precise disassembly of the extracellular matrix of some plant species used as
      feedstocks for bioenergy production continues to be a major barrier to reach
      reasonable cost effective bioethanol production. One solution has been the use of
      pretreatments, which can be effective, but increase even more the cost of
      processing and also lead to loss of cell wall materials that could otherwise be
      used in industry. Although pectins are known to account for a relatively low
      proportion of walls of grasses, their role in recalcitrance to hydrolysis has
      been shown to be important. In this mini-review, we examine the importance of
      pectins for cell wall hydrolysis highlighting the work associated with bioenergy.
      Here we focus on the importance of endopolygalacturonases (EPGs) discovered to
      date. The EPGs cataloged by CAZy were screened, revealing that most sequences, as
      well as the scarce structural work performed with EPGs, are from fungi (mostly
      Aspergillus niger). The comparisons among the EPG from different microorganisms,
      suggests that EPGs from bacteria and grasses display higher similarity than each
      of them with fungi. This compilation strongly suggests that structural and
      functional studies of EPGs, mainly from plants and bacteria, should be a priority
      of research regarding the use of pectinases for bioenergy production purposes.

PMID- 27703464
TI  - Genome-wide Association Study Identifies New Loci for Resistance to Sclerotinia
      Stem Rot in Brassica napus.
AB  - Sclerotinia stem rot (SSR) caused by the necrotrophic fungus Sclerotinia
      sclerotiorum is a major disease in rapeseed (Brassica napus) worldwide. Breeding
      for SSR resistance in B. napus, as in other crops, relies only on germplasms with
      quantitative resistance genes. A better understanding of the genetic basis for
      SSR resistance in B. napus thus holds promise for the genetic improvement of
      disease resistance. In the present study, a genome-wide association study (GWAS)
      for SSR resistance in B. napus were performed using an association panel of 448
      accessions genotyped with the Brassica 60K Infinium(r) single-nucleotide
      polymorphism (SNP) array. A total of 26 SNPs corresponding to three loci, DSRC4,
      DSRC6, and DSRC8 were associated with SSR resistance. Haplotype analysis showed
      that the three favorable alleles for SSR resistance exhibited cumulative effects.
      After aligning SSR resistance quantitative trait loci (QTL) identified in the
      present and previous studies to the B. napus reference genome, one locus (DSRC6)
      was found to be located within the confidence interval of a QTL identified in
      previous QTL mapping studies and another two loci (DSRC4 and DSRC8) were
      considered novel loci for SSR resistance. A total of 39 candidate genes were
      predicted for the three loci based on the GWAS combining with the differentially
      expressed genes identified in previous transcriptomics analyses.

PMID- 27703465
TI  - Using the Disease State Fingerprint Tool for Differential Diagnosis of
      Frontotemporal Dementia and Alzheimer's Disease.
AB  - BACKGROUND: Disease State Index (DSI) and its visualization, Disease State
      Fingerprint (DSF), form a computer-assisted clinical decision making tool that
      combines patient data and compares them with cases with known outcomes. AIMS: To
      investigate the ability of the DSI to diagnose frontotemporal dementia (FTD) and
      Alzheimer's disease (AD). METHODS: The study cohort consisted of 38 patients with
      FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive
      pathology was available for 14 and AD pathology for 12 cases. We utilized data
      from neuropsychological tests, volumetric magnetic resonance imaging, single
      photon emission tomography, cerebrospinal fluid biomarkers and the APOE genotype.
      The DSI classification results were calculated with a combination of leave-one
      out cross-validation and bootstrapping. A DSF visualization of a FTD patient is
      presented as an example. RESULTS: The DSI distinguishes controls from FTD (area
      under the receiver-operator curve, AUC = 0.99) and AD (AUC = 1.00) very well and
      achieves a good differential diagnosis between AD and FTD (AUC = 0.89). In
      subsamples of autopsy-confirmed cases (AUC = 0.97) and clinically diagnosed cases
      (AUC = 0.94), differential diagnosis of AD and FTD performs very well.
      CONCLUSIONS: DSI is a promising computer-assisted biomarker approach for aiding
      in the diagnostic process of dementing diseases. Here, DSI separates controls
      from dementia and differentiates between AD and FTD.

PMID- 27703466
TI  - Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation
      Carriers.
AB  - BACKGROUND: Pathogenic mutations in the granulin gene (GRN) are causative in 5
      10% of patients with frontotemporal dementia (FTD), mostly leading to reduced
      progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing
      PGRN levels. METHODS: Fluctuations in plasma PGRN (n = 41) and its relationship
      with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide
      polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and
      controls. RESULTS: Plasma PGRN levels were lower in carriers than in controls and
      showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although
      plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma
      only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622
      genotypes only partly explained the variability of PGRN levels between subjects.
      CONCLUSIONS: Plasma PGRN is relatively stable over 1 week and therefore seems
      suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN
      only moderately correlated with CSF PGRN, CSF sampling will additionally be
      needed in therapeutic trials.

PMID- 27703467
TI  - Modifiable Factors Associated with Cognitive Impairment in 1,143 Japanese
      Outpatients: The Project in Sado for Total Health (PROST).
AB  - BACKGROUND/AIMS: Evidence on modifiable factors associated with cognitive
      impairment in Japanese patients is scarce. This study aimed to determine
      modifiable factors for cognitive impairment in a Japanese hospital-based
      population. METHODS: Subjects of this cross-sectional study were 1,143 patients
      of Sado General Hospital (Niigata, Japan) registered in the Project in Sado for
      Total Health (PROST) between June 2008 and September 2014. We assessed disease
      history, body mass index (BMI), leisure time physical activity, walking time,
      smoking and drinking habits, and consumption of vegetables, fruits, and green tea
      as predictors, with cognitive impairment defined by the Mini-Mental State
      Examination (score <24) as an outcome. Multiple logistic regression analysis was
      performed to calculate odds ratios (ORs) for cognitive impairment. RESULTS: The
      mean subject age was 68.9 years, and the prevalence of cognitive impairment was
      21.5%. Multivariate analysis revealed that age (p < 0.001), low BMI (<21.1; OR
      1.39, 95% CI 1.12-1.72), a history of stroke (p = 0.003), a history of myocardial
      infarction (p = 0.038), low fruit consumption (p for trend = 0.012), and low
      green tea consumption (p for trend = 0.032) were independently associated with a
      higher prevalence of cognitive impairment. CONCLUSIONS: Modifiable factors, such
      as low BMI, low fruit consumption, and low green tea consumption, are associated
      with cognitive impairment. Longitudinal studies will be needed to confirm these
      findings.

PMID- 27703468
TI  - Decreased Physical Activity Associated with Executive Dysfunction Correlates with
      Cognitive Impairment among Older Adults in the Community: A Retrospective
      Analysis from the Kurihara Project.
AB  - BACKGROUND/AIMS: No previous studies have explored the relationship between
      physical activity (PA) and executive dysfunction. METHODS: We retrospectively
      evaluated the PA for 590 older participants in the Kurihara Project; 221
      participants had a Clinical Dementia Rating (CDR) of 0 (healthy), 295 CDR 0.5
      (very mild dementia), and 74 CDR 1+ (dementia). RESULTS: In the complicated task,
      whether the motor intensity was high (e.g. farming) or low (e.g. shopping), PA
      exhibited an inverse relationship with the CDR level. By contrast, for simple
      tasks with high intensity (e.g. walking), no CDR group differences were noted.
      For PA with low intensity (e.g. cleaning), the CDR 1+ group exhibited decreased
      levels. CONCLUSION: PA was related to the burden of executive function in
      patients with mild cognitive impairment; however, in patients with dementia, PA
      was related to both the burden of executive function and motor intensity.

PMID- 27703469
TI  - Does Schizophrenia in Offspring Increase the Risk of Developing Alzheimer's
      Dementia.
AB  - BACKGROUND/AIMS: Prior studies have consistently found a higher risk of dementia
      in individuals with schizophrenia, but whether this is due to a common etiology
      between the disorders remains obscure. We wanted to elucidate this association by
      investigating whether schizophrenia in offspring increases the risk of
      Alzheimer's dementia. METHODS: All individuals born between 1930 and 1953 were
      identified through national registers and followed from their 50th birthday until
      the date of Alzheimer's dementia, death or end of the study. Regressions were
      performed to evaluate the association between offspring with schizophrenia and
      Alzheimer's dementia. RESULTS: Individuals with offspring with schizophrenia did
      not have an increased risk of Alzheimer's dementia [incidence rate ratio (IRR),
      0.97; 95% CI, 0.88-1.07] compared to individuals with offspring without
      psychiatric contact. This finding remained stable when evaluating early-onset
      (IRR, 1.10; 95% CI, 0.91-1.31) and late-onset Alzheimer's dementia (IRR, 0.92;
      95% CI, 0.88-1.07). Similar findings were made for vascular and unspecified
      dementia. CONCLUSION: The finding of no familial coaggregation between
      schizophrenia and Alzheimer's dementia may suggest that no common etiology
      between the disorders exists. This may indicate that the excess risk of dementia
      in individuals with schizophrenia is a by-product of the higher rates of somatic
      comorbidity and adverse health risk factors among these individuals.

PMID- 27703470
TI  - Qualitative Assessment of Instrumental Activities of Daily Living in Older
      Persons with Very Mild Dementia: The Kurihara Project.
AB  - BACKGROUND/AIMS: We investigated quantitative/qualitative changes of instrumental
      activities of daily living (IADL) in people with a Clinical Dementia Rating (CDR)
      of 0.5. METHODS: IADLs were evaluated in older residents: CDR of 0 (healthy) and
      CDR 0.5 (questionable/very mild dementia). The subjects with CDR 0.5 were divided
      into 2 types: the very mild Alzheimer's disease (vmAD) type and the other type
      including very mild subcortical vascular dementia. IADLs were evaluated
      quantitatively using the Lawton and the original qualitative IADL scales.
      RESULTS: CDR 0.5/vmAD type subjects had impairment of only one Lawton item
      (Shopping) compared to CDR 0 subjects. However, the CDR 0.5/vmAD type group and
      the CDR 0.5/other type group showed impairment of 3 items in the qualitative
      assessment (Shopping, Food preparation, and Mode of transportation). CONCLUSION:
      We suggest using both quantitative/qualitative IADL scales for assessing older
      adults with very mild dementia.

PMID- 27703471
TI  - Clinical Recommendations for the Use of Donepezil 23 mg in Moderate-to-Severe
      Alzheimer's Disease in the Asia-Pacific Region.
AB  - BACKGROUND: The 'Asia-Pacific Expert Panel (APEX) for donepezil 23 mg' met in
      November 2015 to review evidence for the recently approved high dose of donepezil
      and to provide recommendations to help physicians in Asia make informed clinical
      decisions about using donepezil 23 mg in patients with moderate-to-severe
      Alzheimer's disease (AD). SUMMARY: In a global phase III study (study 326) in
      patients with moderate-to-severe AD, donepezil 23 mg/day demonstrated
      significantly greater cognitive benefits versus donepezil 10 mg/day, with a
      between-treatment difference in mean change in the Severe Impairment Battery
      score of 2.2 points (p < 0.001) in the overall population and 3.1 points (p <
      0.001) in patients with advanced AD. A subanalysis of study 326 demonstrated that
      the benefits and risks associated with donepezil 23 mg/day versus donepezil 10
      mg/day in Asian patients with moderate-to-severe AD were comparable to those in
      the global study population. KEY MESSAGE: Donepezil 23 mg is a valuable treatment
      for patients with AD, particularly those with advanced disease. The APEX
      emphasized the importance of patient selection (AD severity, tolerability of
      lower doses of donepezil, and absence of contraindications), a stepwise titration
      strategy for dose escalation, and appropriate monitoring and counseling of
      patients and caregivers in the management of patients with AD.

PMID- 27703472
TI  - Physical Fitness in Older People Recently Diagnosed with Cognitive Impairment
      Compared to Older People Recently Discharged from Hospital.
AB  - BACKGROUND/AIMS: There is evidence of an association between cognitive function
      and physical fitness. The aim of this study was to compare physical fitness in
      patients with cognitive impairment with a group of older people recently
      discharged from hospital. METHODS: A cross-sectional study with 98 patients
      recently diagnosed with cognitive impairment and 115 patients recently discharged
      from hospital. Associations between the study group variable and different
      components in the Senior fitness test were examined, controlling for demographic
      factors and comorbidity. RESULTS: The group recently diagnosed with cognitive
      impairment indicated poorer results on three of six physical fitness components
      (p < 0.05). CONCLUSION: Older adults with cognitive impairment are in need of
      individually tailored physical activity programs to increase the level of
      physical fitness.

PMID- 27703474
TI  - Endoscopic Closure for EUS and ERCP Related Duodenal Perforation by Endoclips.
AB  - Objective. To investigate the therapeutic safety, feasibility, and efficacy of
      endoclips for closing the endoscopic ultrasound (EUS) and endoscopic retrograde
      cholangiopancreatography (ERCP) related duodenal perforation in a retrospective
      study from a single center. Methods. Patients who developed EUS and ERCP related
      duodenal perforation between January 2012 and January 2015 were included in the
      study. All the cases underwent endoscopic closure by endoclips, and the efficacy,
      feasibility, and safety of this technique were evaluated. Results. During the
      study period, a total of 17,406 patients were treated by EUS and/or ERCP. EUS and
      ERCP related duodenal perforation occurred in 9 cases (0.05%): 2 males and 7
      females. The mean age was 69 years (range: 59-79 years). The success rate of
      endoscopic closure by endoclips was 100%. The mean procedure time was 45 +/- 12.5
      min. The mean number of endoclips placed for the closure of the duodenal
      perforation was 7 +/- 3.2. All the patients recovered completely without any
      severe complications. Conclusion. The endoscopic closure by using endoclips is
      recommended as the first-line treatment for duodenal perforation associated with
      EUS and ERCP.

PMID- 27703475
TI  - Evaluation of "Dream Herb," Calea zacatechichi, for Nephrotoxicity Using Human
      Kidney Proximal Tubule Cells.
AB  - A recent surge in the use of dietary supplements, including herbal remedies,
      necessitates investigations into their safety profiles. "Dream herb," Calea
      zacatechichi, has long been used in traditional folk medicine for a variety of
      purposes and is currently being marketed in the US for medicinal purposes,
      including diabetes treatment. Despite the inherent vulnerability of the renal
      system to xenobiotic toxicity, there is a lack of safety studies on the
      nephrotoxic potential of this herb. Additionally, the high frequency of diabetes
      associated kidney disease makes safety screening of C. zacatechichi for safety
      especially important. We exposed human proximal tubule HK-2 cells to increasing
      doses of this herb alongside known toxicant and protectant control compounds to
      examine potential toxicity effects of C. zacatechichi relative to control
      compounds. We evaluated both cellular and mitochondrial functional changes
      related to toxicity of this dietary supplement and found that even at low doses
      evidence of cellular toxicity was significant. Moreover, these findings
      correlated with significantly elevated levels of nephrotoxicity biomarkers,
      lending further support for the need to further scrutinize the safety of this
      herbal dietary supplement.

PMID- 27703476
TI  - Diet-Related Knowledge and Physical Activity in a Large Cohort of Insulin-Treated
      Type 2 Diabetes Patients: PROGENS ARENA Study.
AB  - There is no doubt that behavioral intervention is crucial for type 2 diabetes
      mellitus (T2DM) prevention and management. We aimed to estimate dietary habits
      and diet-oriented knowledge as well as the level of physical activity in 2500
      insulin-treated Polish type 2 diabetes mellitus (T2DM) patients (55.4% women).
      The mean age of the study participants was 64.9 +/- 9.3 years, mean BMI was 31.4
      kg/m2 +/- 4.5, mean diabetes duration was 12.4 +/- 6.9 years, and mean baseline
      HbA1c was 8.5%  +/- 1.2. At the study onset, all the patients completed a
      questionnaire concerning health-oriented behavior. Results showed a significant
      lack of diet-related knowledge. For example, only 37.5% recognized that buckwheat
      contains carbohydrates; the percentage of correct answers in questions about
      fruit drinks and pasta was 56.4% and 61.2%, respectively. As for the physical
      activity, only 57.4% of examined T2DM patients declared any form of deliberate
      physical activity. To conclude, the cohort of poorly controlled insulin-treated
      T2DM patients studied by us is characterized by insufficient diet-related
      knowledge and by a very low level of physical activity. Further studies on other
      populations of insulin-treated T2DM patients are required to confirm these
      findings.

PMID- 27703477
TI  - Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular
      Endothelial Cells of Type 2 Diabetic Rats.
AB  - In the study, type 2 diabetic rat model was established using streptozotocin
      (STZ) combined with a high-fat diet, and the rats were divided into control and
      diabetic groups. Diabetic groups were further divided into nonintervening,
      simvastatin, Didang Decoction (DDD) early-phase intervening, DDD mid-phase
      intervening, and DDD late-phase intervening groups. The expression level of MLCK
      was detected using Western Blot analysis, and the levels of cyclic adenosine
      monophosphate (cAMP), protein kinase C (PKC), and protein kinase A (PKA) were
      examined using Real Time PCR. Under the electron microscope, the cells in the
      early-DDD-intervention group and the simvastatin group were significantly more
      continuous and compact than those in the diabetic group. Compared with the
      control group, the expression of cAMP-1 and PKA was decreased in all diabetic
      groups, whereas the expression of MLCK and PKC was increased in early- and mid
      phase DDD-intervening groups (P < 0.05); compared with the late-phase DDD
      intervening group, the expression of cAMP-1 and PKA was higher, but the level of
      MLCK and PKC was lower in early-phase DDD-intervening group (P < 0.05). In
      conclusion, the early use of DDD improves the permeability of vascular
      endothelial cells by regulating the MLCK signaling pathway.

PMID- 27703473
TI  - Gender Differences in Adipocyte Metabolism and Liver Cancer Progression.
AB  - Liver cancer is the third most common cancer type and the second leading cause of
      deaths in men. Large population studies have demonstrated remarkable gender
      disparities in the incidence and the cumulative risk of liver cancer. A number of
      emerging risk factors regarding metabolic alterations associated with obesity,
      diabetes and dyslipidemia have been ascribed to the progression of non-alcoholic
      fatty liver diseases (NAFLD) and ultimately liver cancer. The deregulation of fat
      metabolism derived from excessive insulin, glucose, and lipid promotes cancer
      causing inflammatory signaling and oxidative stress, which eventually triggers
      the uncontrolled hepatocellular proliferation. This review presents the current
      standing on the gender differences in body fat compositions and their mechanistic
      linkage with the development of NAFLD-related liver cancer, with an emphasis on
      genetic, epigenetic and microRNA control. The potential roles of sex hormones in
      instructing adipocyte metabolic programs may help unravel the mechanisms
      underlying gender dimorphism in liver cancer and identify the metabolic targets
      for disease management.

PMID- 27703478
TI  - Corrigendum to "Ferritin as a Risk Factor for Glucose Intolerance amongst Men and
      Women Originating from the Indian Subcontinent".
AB  - [This corrects the article DOI: 10.1155/2015/924387.].

PMID- 27703479
TI  - PCR-Based Identification of Oral Streptococcal Species.
AB  - The microbial etiology of dental caries is still debated. Among the hypothesized
      contributors are the "low pH streptococci," a designation given to unusually acid
      proficient strains among the primary plaque colonizers S. oralis, S. mitis, S.
      gordonii, and S. anginosus. However, accurate assignment of species is difficult
      among the oral streptococci. Our objective was to develop a streamlined method
      for identifying strains of S. oralis and S. mitis from plaque samples so that
      they could be analyzed in a separate study devoted to low pH streptococci and
      caries. Two independent PCR amplifications of a locus highly conserved among
      streptococci were used for presumptive species identification. Multilocus
      sequence analysis (MLSA) was used to measure accuracy. Sensitivity was 100% for
      selecting S. oralis and S. mitis among the clones sampled. Specificity was good
      except for the most closely related species that could not be reliably
      distinguished even by MLSA. The results with S. oralis and S. mitis were used to
      identify new primer sets that expanded the utility of the approach to other oral
      streptococcal species. These novel primer sets offer a convenient means of
      presumptive identification that will have utility in many studies where large
      scale, in-depth genomic analyses are not practical.

PMID- 27703480
TI  - Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle Cell Trait among
      Prospective Blood Donors: A Cross-Sectional Study in Berekum, Ghana.
AB  - Background. Blood transfusion is a therapeutic procedure usually undertaken in
      patients with severe anaemia. In Ghana, severe anaemia is mostly due to malaria
      caused by severe Plasmodium falciparum infection, road traffic accidents, and
      haemoglobinopathy-induced acute haemolysis. Method. This cross-sectional study
      evaluated coinheritance of sickle cell haemoglobin variant and G6PD enzymopathy
      among individuals that donated blood at the Holy Trinity Hospital, Berekum, in
      the Brong-Ahafo Region, Ghana. Demographic data and other pertinent information
      were captured using questionnaire. Sickle cell haemoglobin variants were
      determined using cellulose acetate electrophoresis (pH 8.6). Qualitative G6PD
      status and quantitative G6PD enzyme activity were determined using methaemoglobin
      reduction and Trinity Biotech G6PD test kit, respectively. Results. Prevalence of
      sickle cell trait (SCT) and G6PD enzymopathy coinheritance was 7%. In addition,
      19.5% of the donors had 10%-60% of normal G6PD enzyme activity suggesting that
      these donor units are prone to stressor-induced acute haemolysis when given to
      recipients. Mild G6PD activity (p = 0.03, OR: 2.410 (CI: 1.049-5.534)),
      commercial (p = 0.020, OR: 5.609 (CI: 1.309-24.035)), and voluntary (p = 0.034,
      OR: 2.404 (CI: 1.071-5.397)) donors were significantly associated with SCT.
      Conclusion. Screening for red cell pathologies must be incorporated into existing
      protocols for populations with high incidence of haemoglobinopathies to protect
      high-risk recipients.

PMID- 27703481
TI  - Comment on "Bacteria in Cancer Therapy: Renaissance of an Old Concept".

PMID- 27703482
TI  - Determinants of Antenatal Care Attendance among Pregnant Women Living in Endemic
      Malaria Settings: Experience from the Democratic Republic of Congo.
AB  - Background. Antenatal care (ANC) attendance helps pregnant women to benefit from
      preventive and curative services. Methods. Determinants for ANC attendance were
      identified through a cross-sectional survey in the Democratic Republic of Congo.
      Sociocultural bottlenecks were assessed via focus groups discussion of married
      men and women. Results. In this survey, 28 of the 500 interviewed pregnant women
      (5.6%) did not attend ANC services and 82.4% booked over the first trimester. The
      first visit is positively influenced by the reproductive age (OR: 0.52, 95%
      CI(0.28-0.95), p < 0.04), the educational level (OR: 0.41,95% CI(0.17-0.97), p <
      0.04), the nearby health center (OR: 0.43, 95% CI(0.2-0.92), p < 0.03), and the
      presence of a male partner (OR: 10.48, 95% CI(2.1-52.23), p < 0.001). The
      barriers to early booking were (i) the cost of service; (ii) the appearance or
      individual income; (iii) the geographical inaccessibility or distance to health
      facilities; (iv) social and religious prohibitions; (v) the stigmatization from
      other women when conceiving in the late ages or young or while still lactating
      (parity); (vi) the time for waiting for services. Conclusion. The early ANC
      attendance is delayed among poor women with little education and living alone.

PMID- 27703483
TI  - The Association of Pseudohypoparathyroidism Type Ia with Chiari Malformation Type
      I: A Coincidence or a Common Link?
AB  - A 19-month-old boy was referred for progressive weight gain. His past medical
      history included congenital hypothyroidism and developmental delay. Physical
      examination revealed characteristics of Albright Hereditary Osteodystrophy,
      macrocephaly, and calcinosis cutis. He had hypocalcemia, hyperphosphatemia, and
      elevated Parathyroid Hormone levels. Genetic testing revealed a known mutation of
      GNAS gene, confirming the diagnosis of Pseudohypoparathyroidism Type Ia (PHP-Ia)
      (c.34C>T (p.G1n12X)). He had a normal brain MRI at three months, but
      developmental delay prompted a repeat MRI that revealed Chiari Malformation Type
      I (CM-I) with hydrocephalus requiring neurosurgical intervention. This was
      followed by improvement in attaining developmental milestones. Recently, he was
      diagnosed with growth hormone deficiency. This case suggests the potential
      association of CM-I with PHP-Ia. Larger studies are needed to assess whether CM-I
      with hydrocephalus are common associations with PHP-Ia and to define potential
      genetic links between these conditions. We propose a low threshold in performing
      brain MRI on PHP-1a patients, especially those with persistent developmental
      delay to rule out CM-I. Early intervention may improve neurodevelopmental
      outcomes and prevent neurosurgical emergencies.

PMID- 27703484
TI  - Targeted Strategies to Modulate Stem-Cell-Relevant Pathways.

PMID- 27703485
TI  - Differential Characterization of Two Kinds of Stem Cells Isolated from Rabbit
      Nucleus Pulposus and Annulus Fibrosus.
AB  - Objective. Nucleus pulposus (NP) and annulus fibrosus (AF) are two main
      components of intervertebral disc (IVD). We aimed to figure out whether NP and AF
      also contain stem cells and whether these stem cells share common properties with
      chondrocytes and/or fibroblasts in their phenotypes or whether they are
      completely different types of cells with different characteristics. Design. The
      disk cells were isolated from AF and NP tissues of the same lumbar spine of the
      rabbits. The properties of these disk cells were characterized by their
      morphology, population doubling time (PDT), stem cell marker expression, and
      multidifferentiation potential using tissue culture techniques,
      immunocytochemistry, and RT-PCR. Results. Both disk cells formed colonies in
      culture and expressed stem cell markers, nucleostemin, Oct-4, SSEA-4, and Stro-1,
      at early passages. However, after 5 passages, AFSCs became elongated and NPSCs
      appeared senescent. Conclusion. This study indicated that IVD contains stem cells
      and the characteristics of AFSCs and NPSCs are intrinsically different. The
      findings of this study may provide basic scientific data for understanding the
      properties of IVD cells and the mechanisms of lower back pain.

PMID- 27703486
TI  - Retracted: The Antioxidant and Starch Hydrolase Inhibitory Activity of Ten Spices
      in an In Vitro Model of Digestion: Bioaccessibility of Anthocyanins and
      Carotenoids.
AB  - [This retracts the article DOI: 10.1155/2015/764238.].

PMID- 27703488
TI  - Personalized Kampo Medicine Facilitated Both Cytotoxic T Lymphocyte Response and
      Clinical Benefits Induced by Personalized Peptide Vaccination for Advanced
      Esophageal Cancer.
AB  - We retrospectively evaluated if personalized Kampo medicine (PKM) could
      facilitate CTL responses and clinical benefits induced by personalized peptide
      vaccination (PPV), in which HLA-matched vaccines were selected and administered
      based on the preexisting host immunity, for advanced esophageal cancer (aEC)
      patients. Among 34 aEC patients entered in the clinical study, 23 patients
      received PKM and PPV without (n = 12) or with chemotherapy (n = 11), while the
      remaining 11 patients did not receive PKM but received PPV without (n = 6) or
      with chemotherapy (n = 5), respectively. Incidence of adverse events was
      significantly lower or higher in PKM and PPV arm (n = 23) or PPV and chemotherapy
      arm (n = 16) as compared to that of the counter arm (n = 11 or 18), respectively.
      Postvaccination PBMCs from the patients undergoing PKM and PPV showed
      significantly higher CTL responses as compared to the counter arm. The median
      progression-free survival (PFS) or median survival time (MST) of 34 patients was
      2.9 or 7.6 months, respectively. The combination therapy in PPV and PKM arm, but
      not that in PPV and chemotherapy arm, significantly (P = 0.02) prolonged MST.
      These results could warrant a next step of prospective clinical study of PKM and
      PPV for aEC patients.

PMID- 27703490
TI  - Natural Products for the Treatment of Obesity, Metabolic Syndrome, and Type 2
      Diabetes 2016.

PMID- 27703487
TI  - Anti-Inflammatory Effects of Traditional Chinese Medicines against Ischemic
      Injury in In Vivo Models of Cerebral Ischemia.
AB  - Inflammation plays a crucial role in the pathophysiology of acute ischemic
      stroke. In the ischemic cascade, resident microglia are rapidly activated in the
      brain parenchyma and subsequently trigger inflammatory mediator release, which
      facilitates leukocyte-endothelial cell interactions in inflammation. Activated
      leukocytes invade the endothelial cell junctions and destroy the blood-brain
      barrier integrity, leading to brain edema. Toll-like receptors (TLRs) stimulation
      in microglia/macrophages through the activation of intercellular signaling
      pathways secretes various proinflammatory cytokines and enzymes and then
      aggravates cerebral ischemic injury. The secreted cytokines activate the
      proinflammatory transcription factors, which subsequently regulate cytokine
      expression, leading to the amplification of the inflammatory response and
      exacerbation of the secondary brain injury. Traditional Chinese medicines (TCMs),
      including TCM-derived active compounds, Chinese herbs, and TCM formulations,
      exert neuroprotective effects against inflammatory responses by downregulating
      the following: ischemia-induced microglial activation, microglia/macrophage
      mediated cytokine production, proinflammatory enzyme production, intercellular
      adhesion molecule-1, matrix metalloproteinases, TLR expression, and deleterious
      transcription factor activation. TCMs also aid in upregulating anti-inflammatory
      cytokine expression and neuroprotective transcription factor activation in the
      ischemic lesion in the inflammatory cascade during the acute phase of cerebral
      ischemia. Thus, TCMs exert potent anti-inflammatory properties in ischemic stroke
      and warrant further investigation.

PMID- 27703489
TI  - Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting
      Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway.
AB  - Doxorubicin (Dox) is one of the most effective and widely used anthracycline
      antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its
      cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid
      which is isolated from the ground bark of Myrica rubra, has recently been found
      to have a strong antioxidative effect. This study aimed to evaluate the possible
      protective effect of myricitrin against Dox-induced cardiotoxicity and the
      underlying mechanisms. An in vivo investigation in SD rats demonstrated that
      myricitrin significantly reduced the Dox-induced myocardial damage, as indicated
      by the decreases in the cardiac index, amelioration of heart pathological
      injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro
      studies showed that myricitrin effectively reduced the Dox-induced cell toxicity.
      Further study showed that myricitrin exerted its function by counteracting
      oxidative stress and increasing the activities of antioxidant enzymes. Moreover,
      myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by
      decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells,
      maintenance of the mitochondrial membrane potential, and increase in the Bcl
      2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression
      of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis
      pathway.

PMID- 27703491
TI  - Computational Hemodynamic Analysis for the Diagnosis of Atherosclerotic Changes
      in Intracranial Aneurysms: A Proof-of-Concept Study Using 3 Cases Harboring
      Atherosclerotic and Nonatherosclerotic Aneurysms Simultaneously.
AB  - This was a proof-of-concept computational fluid dynamics (CFD) study designed to
      identify atherosclerotic changes in intracranial aneurysms. We selected 3
      patients with multiple unruptured aneurysms including at least one with
      atherosclerotic changes and investigated whether an image-based CFD study could
      provide useful information for discriminating the atherosclerotic aneurysms.
      Patient-specific geometries were constructed from three-dimensional data obtained
      using rotational angiography. Transient simulations were conducted under patient
      specific inlet flow rates measured by phase-contrast magnetic resonance
      velocimetry. In the postanalyses, we calculated time-averaged wall shear stress
      (WSS), oscillatory shear index, and relative residence time (RRT). The volume of
      blood flow entering aneurysms through the neck and the mean velocity of blood
      flow inside aneurysms were examined. We applied the age-of-fluid method to
      quantitatively assess the residence of blood inside aneurysms. Atherosclerotic
      changes coincided with regions exposed to disturbed blood flow, as indicated by
      low WSS and long RRT. Blood entered aneurysms in phase with inlet flow rates. The
      mean velocities of blood inside atherosclerotic aneurysms were lower than those
      inside nonatherosclerotic aneurysms. Blood in atherosclerotic aneurysms was older
      than that in nonatherosclerotic aneurysms, especially near the wall. This proof
      of-concept study demonstrated that CFD analysis provided detailed information on
      the exchange and residence of blood that is useful for the diagnosis of
      atherosclerotic changes in intracranial aneurysms.

PMID- 27703492
TI  - A Fetal Electrocardiogram Signal Extraction Algorithm Based on Fast One-Unit
      Independent Component Analysis with Reference.
AB  - Fetal electrocardiogram (FECG) extraction is very important procedure for fetal
      health assessment. In this article, we propose a fast one-unit independent
      component analysis with reference (ICA-R) that is suitable to extract the FECG.
      Most previous ICA-R algorithms only focused on how to optimize the cost function
      of the ICA-R and payed little attention to the improvement of cost function. They
      did not fully take advantage of the prior information about the desired signal to
      improve the ICA-R. In this paper, we first use the kurtosis information of the
      desired FECG signal to simplify the non-Gaussian measurement function and then
      construct a new cost function by directly using a nonquadratic function of the
      extracted signal to measure its non-Gaussianity. The new cost function does not
      involve the computation of the difference between the function of the Gaussian
      random vector and that of the extracted signal, which is time consuming.
      Centering and whitening are also used to preprocess the observed signal to
      further reduce the computation complexity. While the proposed method has the same
      error performance as other improved one-unit ICA-R methods, it actually has lower
      computation complexity than those other methods. Simulations are performed
      separately on artificial and real-world electrocardiogram signals.

PMID- 27703493
TI  - Analysis of Blood Transfusion Data Using Bivariate Zero-Inflated Poisson Model: A
      Bayesian Approach.
AB  - Recognizing the factors affecting the number of blood donation and blood deferral
      has a major impact on blood transfusion. There is a positive correlation between
      the variables "number of blood donation" and "number of blood deferral": as the
      number of return for donation increases, so does the number of blood deferral. On
      the other hand, due to the fact that many donors never return to donate, there is
      an extra zero frequency for both of the above-mentioned variables. In this study,
      in order to apply the correlation and to explain the frequency of the excessive
      zero, the bivariate zero-inflated Poisson regression model was used for joint
      modeling of the number of blood donation and number of blood deferral. The data
      was analyzed using the Bayesian approach applying noninformative priors at the
      presence and absence of covariates. Estimating the parameters of the model, that
      is, correlation, zero-inflation parameter, and regression coefficients, was done
      through MCMC simulation. Eventually double-Poisson model, bivariate Poisson
      model, and bivariate zero-inflated Poisson model were fitted on the data and were
      compared using the deviance information criteria (DIC). The results showed that
      the bivariate zero-inflated Poisson regression model fitted the data better than
      the other models.

PMID- 27703494
TI  - Alterations of caveolin-1 expression in a mouse model of delayed cerebral
      vasospasm following subarachnoid hemorrhage.
AB  - The aim of the present study was to evaluate the expression levels of caveolin-1
      in the basilar artery following delayed cerebral vasospasm (DCVS) in a rat model
      of subarachnoid hemorrhage (SAH), in order to investigate the association between
      caveolin-1 and DCVS, and its potential as a treatment for DCVS of SAH. A total of
      150 Sprague Dawley rats were randomly allocated into blank, saline and SAH
      groups. The SAH and saline groups were subdivided into days 3, 5, 7 and 14
      following the establishment of the model. The murine model of SAH was established
      by double injection of autologous arterial blood into the cisterna magana and
      DCVS was detected using Bederson neurological severity scores. Hematoxylin and
      eosin (HE) staining was used to observe the inner perimeter of the basilar artery
      pipe and variations in the thickness of the basilar artery wall. Alterations in
      the levels of caveolin-1 protein in the basilar artery were measured using
      immunofluorescence and western blot analysis; whereas alterations in the mRNA
      expression levels of caveolin-1 were detected by reverse transcription
      quantitative polymerase chain reaction. In the present study, 15 mice succumbed
      to SAH-induced DCVS in the day 3 (n=3), 5 (n=5) and 7 (n=2) groups. No mortality
      was observed in the blank control and saline groups during the process of
      observation in the SAH group, All mice in the SAH groups exhibited Bederson
      neurological severity scores >=1; whereas no neurological impairment was detected
      in the blank and normal saline groups, demonstrating the success of the model. HE
      staining was used to assess vasospasm and the results demonstrated that the inner
      perimeter of the basal artery pipe decreased at day 3 in the SAH group; whereas
      values peaked in the day 7 group. The thickness of the basal artery wall
      significantly increased (P<0.05), as compared with the blank and saline groups,
      in which no significant alterations in the wall thickness and the inner perimeter
      of the basal artery pipe were detected. As detected by immunofluorescence and
      western blot analysis, the expression levels of caveolin-1 protein significantly
      decreased in the day 7 of SAH group, as compared with the blank and saline groups
      (P<0.01), in which no significant alterations were detected. Caveolin-1 mRNA
      expression levels significantly increased at the day 7 in the SAH group, as
      compared with the blank and the saline groups (P<0.01), as detected by RT-qPCR.
      Furthermore, significant differences were detected at day 14 in the SAH group, as
      compared with the blank and the saline groups (P>0.05), in which no significant
      alterations were detected. Therefore, the results of the present study
      demonstrated that caveolin-1 protein was downregulated in the basilar artery of a
      rat modeling SAH, which may be associated with DCVS. This suggested that caveolin
      1 may be a potential target for the treatment of DCVS.

PMID- 27703495
TI  - Identification of hub genes and pathways associated with hepatocellular carcinoma
      based on network strategy.
AB  - The objective of this study was to identify hub genes and pathways associated
      with hepatocellular carcinoma (HCC) by centrality analysis of a co-expression
      network. A co-expression network based on differentially expressed (DE) genes of
      HCC was constructed using the Differentially Co-expressed Genes and Links (DCGL)
      package. Centrality analyses, for centrality of degree, clustering coefficient,
      closeness, stress and betweenness for the co-expression network were performed to
      identify hub genes, and the hub genes were combined together to overcome
      inconsistent results. Enrichment analyses were conducted using Gene Ontology and
      Kyoto Encyclopedia of Genes and Genomes databases. Finally, validation of hub
      genes was conducted utilizing reverse transcription-polymerase chain reaction (RT
      PCR) analysis. In total, 260 DE genes between normal controls and HCC patients
      were obtained and a co-expression network with 154 nodes and 326 edges was
      constructed. From this, 13 hub genes were identified according to degree,
      clustering coefficient, closeness, stress and betweenness centrality analysis. It
      was found that reelin (RELN), potassium voltage-gated channel subfamily J member
      10 (KCNJ10) and neural cell adhesion molecule 1 (NCAM1) were common hub genes
      across the five centralities, and the results of RT-PCR analysis for RELN, KCNJ10
      and NCAM1 were consistent with the centrality analyses. Pathway enrichment
      analysis of DE genes showed that cell cycle, metabolism of xenobiotics by
      cytochrome P450 and p53 signaling pathway were the most significant pathways.
      This study may contribute to understanding the molecular pathogenesis of HCC and
      provide potential biomarkers for its early detection and effective therapies.

PMID- 27703496
TI  - HBD-3 regulation of the immune response and the LPS/TLR4-mediated signaling
      pathway.
AB  - The aim of the study was to investigate the mechanisms of human beta-defensin 3
      (HBD-3) regulation of the immune response and the lipopolysaccharide/Toll-like
      receptor-4 (LPS/TLR4)-mediated signaling pathway. A TLR4 extracellular gene
      fragment was cloned into the pET32a plasmid to determine its expression in
      Escherichia coli (E. coli) and purification. A dialysis labeling method was used
      to stain HBD-3 with fluorescein isothiocyanate (FITC). FITC-HBD-3 was used to
      induce the differentiation of human peripheral blood mononuclear cells (MNC) into
      immature dendritic cells (imDC) in vitro. Binding reactions were established
      using FITC-HBD-3 and sTLR4 into cell suspensions. Flow cytometry (FCM) was used
      to analyze the results. Western blot analysis confirmed the identity of nuclear
      factor-kappaB (NF-kappaB) and was used to quantify its nuclear translocation. The
      results showed that, HBD-3 bound to imDC in a Ca2+-dependent manner, and sTLR4
      and LPS competitively inhibited the binding. HBD-3 competitively blocked the
      binding of LPS and imDC by binding to imDC. HBD-3 significantly decreased the
      translocation of LPS-induced NF-kappaB into the nucleus. In conclusion, HBD-3 can
      competitively inhibit the binding of LPS and imDC through its binding to TLR4
      molecules, which are expressed in imDC, thereby preventing LPS from inducing the
      maturity of the imDCs.

PMID- 27703497
TI  - Chronic myelocytic leukemic fundus lesion: A case report.
AB  - The current study reports a case of a patient with a chronic myelocytic leukemic
      fundus lesion, initially diagnosed in the Department of Ophthalmology, Rizhao
      People's Hospital (Rizhao, China). A male, 23-years-of-age, presented with a dark
      shadow in the front of the right eye, accompanied with blurred vision for 3 days
      (visual acuity of right eye, 0.4; visual acuity of left eye, 0.6). In addition,
      the patient had experienced gingival bleeding for 2 years, and recurrent upper
      respiratory infections for 1 year. A fundus examination revealed mild binocular
      papillary edema, dilated and tortuous veins, and the retina exhibited large
      quantities of scattered and dark red bleeding spots. The bleeding spots had white
      spots in the center, which exhibited typical Roth spots, whilst routine blood
      examination, abdominal ultrasound, marrow biopsy and other laboratory tests
      confirmed the diagnosis of chronic myelogenous leukemia. Patients with leukemia
      typically present with initial symptoms that include fever, fatigue, anemia and
      hepatosplenomegaly, and a diagnosis as a result of eye-related symptoms is rare,
      rendering the present case unique.

PMID- 27703498
TI  - Acute transverse myelitis and subacute thyroiditis associated with dengue viral
      infection: A case report and literature review.
AB  - Acute transverse myelitis is a rare manifestation of dengue infection. To the
      best of our knowledge, only 6 cases of acute transverse myelitis as a
      manifestation of dengue infection have been reported thus far. The present study
      described a case of acute transverse myelitis complicated with subacute
      thyroiditis 6 days after the onset of dengue viral infection. In addition, the
      available literature was searched to identify similar previous cases. Treatment
      with intravenous pulse methylprednisolone immunoglobulin plasmapheresis and
      physiotherapy resulted in partial recovery at 3 months post-infection. In
      conclusion, the involvement of dengue infection should be considered in patients
      who develop central nervous system manifestations during or after the recovery
      period of dengue infection. Furthermore, since methylprednisolone and
      immunoglobulin are effective during the active phase of the infection, prompt
      diagnosis and initiation of treatment are crucial.

PMID- 27703499
TI  - FeNO for detecting lower airway involvement in patients with allergic rhinitis.
AB  - Allergic rhinitis (AR) is a risk factor for asthma development. The value of
      fractional exhaled nitric oxide (FeNO) in detecting lower airway involvement in
      the progress of AR-asthma march has not been evaluated. The aim of the present
      study was to investigate the value of FeNO in assessing lower airway inflammation
      and predicting bronchial hyperresponsiveness (BHR) in AR with or without asthma.
      FeNO and eosinophil count in induced sputum, and a methacholine bronchial
      provocation test were performed in 93 subjects, including: 45 AR patients (AR
      group); 20 patients with AR and asthma (AR with asthma group); and 28 normal
      controls (control group). The AR group was divided into two sub-groups: AR with
      asymptomatic BHR group and AR without BHR group. Correlation between FeNO and
      eosinophil count was assessed. Receiver operating characteristic (ROC) curve was
      applied to evaluate the predictive and diagnostic value of FeNO in detecting BHR.
      The values of FeNO in the AR and AR with asthma groups were higher [29.5 (22.0)
      ppb and 61.5 (33.0) ppb] compared with the normal control group (16.0 (10.0)
      ppb), where the values in brackets indicate the interquartile range of the
      values. The percentages of eosinophils in induced sputum were 2.43+/-3.56, 7.36+/
      4.98 and 18.58+/-11.26% in the control, AR and AR with asthma groups,
      respectively. For the diagnosis of BHR, the area under the curve (AUC) was 0.910
      (95%CI 0.836, 0.984), with the sensitivity and specificity 0.846 and 0.817 when
      the cut-off value takes 31.5 ppb. For diagnosis of asthma, the AUC was 0.873
      (95%CI 0.753, 0.992) with sensitivity 0.857 and specificity 0.847 when taking the
      cut-off value to be 38.0 ppb. The value of FeNO was well correlated with
      eosinophil count in the sputum. The measurement of FeNO is an effective method in
      detecting lower airway involvement in AR developing to asthma.

PMID- 27703500
TI  - Childhood type 2 diabetes: Risks and complications.
AB  - The universal endocrine pathological state affecting young individuals and adults
      is type 2 diabetes mellitus, which has seen a significant increase in the last 30
      years, particularly in children. Genetic and evnironmental factors are the
      causative agents for this pathological state in children. This rapid and wide
      spread of the disease can be controlled by enforcing amendments in environmental
      factors such as diet, physical activities and obesity. In young infants
      breastfeeding may be a key modulator of the disease. Associated disorders co
      observed in the patients of type 2 diabetes mellitus include renal failure, heart
      problems and circulatory dysfunctionalities, such as cardiac failure and vision
      disability. These associated disorders become more pronounced in young patients
      when they reach puberty. To overcome the lethal outcomes of the disease, early
      screening of the disease is crucial. The present review focused on the latest
      updates in the field, as well as plausible risks and complications of this
      pathological state.

PMID- 27703503
TI  - Telemedicine in clinical setting.
AB  - The telemedicine department of a hospital is an emerging branch in upcoming
      hospitals and may become an essential component of every hospital. It basically
      utilizes the information technologies along with telecommunication systems in
      order to provide clinical care and assistance. Furthermore, the branch of
      telemedicine offers significant opportunities for the process of developmental
      freedom from illness, early death, and preventable diseases. It advances
      development by providing relevant drugs and the necessary care aimed to alleviate
      patient suffering. It is also beneficial for patients in rural remote areas who
      usually do not have adequate access to advanced hospitals. Telemedicine in these
      remote areas allows for timely treatment of emergency cases. Thus, it contributes
      towards remote emergency critical care in order to save lives in crucial cases.
      Additionally, the emerging advances have now enabled telemedicine to transfer
      large amounts of clinical informatics data including images, and test reports to
      the specifically specialized health professionals in some serious cases. However,
      as in the case of many emerging technologies, organizing information and
      understanding the field has significant challenges. The present review article
      aimed to discuss important aspects of the field with regard to the better
      management of patients in clinical settings.

PMID- 27703501
TI  - Hypersplenism: History and current status.
AB  - Hypersplenism is a common disorder characterized by an enlarged spleen which
      causes rapid and premature destruction of blood cells. This review summarizes the
      history of hypersplenism, discuss its classification and pathogenesis, and
      examines its diagnosis and treatment options. We performed a comprehensive
      literature search using PubMed, Web of Knowledge and the China National Knowledge
      Infrastructure (CNKI) database, reviewed hypersplenism-related articles and
      summarized the major findings. According to its etiological causes, hypersplenism
      is characterized by splenomegaly and peripheral cytopenias. It can be classified
      into three categories: i) primary hypersplenism; ii) secondary hypersplenism; and
      iii) occult hypersplenism. A number of mechanisms causing hypersplenism have been
      identified, and mainly involve retention in the spleen, phagocytosis, and
      autoimmunity. Treatment options for hypersplenism include etiological treatment,
      non-surgical treatment, total splenectomy and liver transplantation. In any case,
      treatment should be individualized for each patient.

PMID- 27703504
TI  - Small hepatocyte-like progenitor cells may be a Hedgehog signaling pathway
      controlled subgroup of liver stem cells.
AB  - The present study aimed to investigate the expression levels of components of the
      Hedgehog signaling pathway (HH) during the proliferation of a liver stem cell
      subgroup, namely small hepatocyte-like progenitor cells (SHPCs). Retrorsine
      treated Fisher 344 rats underwent a partial hepatectomy (PH) to induce the
      proliferation of SHPCs, after which reverse transcription-polymerase chain
      reaction (PCR), quantitative PCR, immunohistochemistry and western blot analysis
      were performed to analyze the expression of various components of the HH in
      primary SHPCs at different times points post-PH. A number of components of the
      HH, including Indian hedgehog (IHH), patched (PTCH), smoothened and glioma
      associated oncogene (GLI)1, 2 and 3, were continuously expressed and showed
      dynamic changes in proliferating SHPCs. In addition, the expression levels of
      IHH, PTCH and GLI1 were significantly different as compared with those of the
      control group at the same time point, and there were significant differences
      among the various time points in the experimental group (P<0.01). Furthermore,
      there was an association between the postoperative day and expression levels of
      HH components in the retrorsine-treated group. An immunohistochemical analysis
      demonstrated that PTCH was also expressed at the protein level. In conclusion,
      the results of the present study suggested that the HH was continuously activated
      during the proliferation of SHPCs, thus indicating that SHPCs may be a subgroup
      of stem cells that are regulated by the HH.

PMID- 27703502
TI  - Obesity and hypertension.
AB  - The imbalance between energy intake and expenditure is the main cause of
      excessive overweight and obesity. Technically, obesity is defined as the abnormal
      accumulation of >=20% of body fat, over the individual's ideal body weight. The
      latter constitutes the maximal healthful value for an individual that is
      calculated based chiefly on the height, age, build and degree of muscular
      development. However, obesity is diagnosed by measuring the weight in relation to
      the height of an individual, thereby determining or calculating the body mass
      index. The National Institutes of Health have defined 30 kg/m2 as the limit over
      which an individual is qualified as obese. Accordingly, the prevalence of obesity
      in on the increase in children and adults worldwide, despite World Health
      Organization warnings. The growth of obesity and the scale of associated health
      issues induce serious consequences for individuals and governmental health
      systems. Excessive overweight remains among the most neglected public health
      issues worldwide, while obesity is associated with increasing risks of
      disability, illness and death. Cardiovascular diseases, the leading cause of
      mortality worldwide, particularly hypertension and diabetes, are the main
      illnesses associated with obesity. Nevertheless, the mechanisms underlying
      obesity-associated hypertension or other associated metabolic diseases remains to
      be adequately investigated. In the present review, we addressed the association
      between obesity and cardiovascular disease, particularly the biological
      mechanisms linking obesity and hypertension.

PMID- 27703505
TI  - Computational approach for predicting the conserved B-cell epitopes of
      hemagglutinin H7 subtype influenza virus.
AB  - An avian-origin influenza H7N9 virus epidemic occurred in China in 2013-2014, in
      which >422 infected people suffered from pneumonia, respiratory distress syndrome
      and septic shock. H7N9 viruses belong to the H7 subtype of avian-origin influenza
      viruses (AIV-H7). Hemagglutinin (HA) is a vital membrane protein of AIV that has
      an important role in host recognition and infection. The epitopes of HA are
      significant determinants of the regularity of epidemic and viral mutation and
      recombination mechanisms. The present study aimed to predict the conserved B-cell
      epitopes of AIV-H7 HA using a bioinformatics approach, including the three most
      effective epitope prediction softwares available online: Artificial Neural
      Network based B-cell Epitope Prediction (ABCpred), B-cell Epitope Prediction
      (BepiPred) and Linear B-cell Epitope Prediction (LBtope). A total of 24 strains
      of Euro-Asiatic AIV-H7 that had been associated with a serious poultry pandemic
      or had infected humans in the past 30 years were selected to identify the
      conserved regions of HA. Sequences were obtained from the National Center for
      Biotechnology Information and Global Initiative on Sharing Avian Influenza Data
      databases. Using a combination of software prediction and sequence comparisons,
      the conserved epitopes of AIV-H7 were predicted and clarified. A total of five
      conserved epitopes [amino acids (aa) 37-52, 131-142, 215-234, 465-484 and 487
      505] with a suitable length, high antigenicity and minimal variation were
      predicted and confirmed. Each obtained a score of >0.80 in ABCpred, 60% in LBtope
      and a level of 0.35 in Bepipred. In addition, a representative amino acid change
      (glutamine235-to-leucine235) in the HA protein of the 2013 AIV-H7N9 was
      discovered. The strategy adopted in the present study may have profound
      implications on the rapid diagnosis and control of infectious disease caused by
      H7N9 viruses, as well as by other virulent viruses, such as the Ebola virus.

PMID- 27703506
TI  - A meta-analysis of the effects of beta-adrenergic blockers in chronic heart
      failure.
AB  - Adrenergic beta-blockers are drugs that bind to, but do not activate beta
      adrenergic receptors. Instead they block the actions of beta-adrenergic agonists
      and are used for the treatment of various diseases such as cardiac arrhythmias,
      angina pectoris, myocardial infarction, hypertension, headache, migraines,
      stress, anxiety, prostate cancer, and heart failure. Several meta-analysis
      studies have shown that beta-blockers improve the heart function and reduce the
      risks of cardiovascular events, rate of mortality, and sudden death through
      chronic heart failure (CHF) of patients. The present study identified results
      from recent meta-analyses of beta-adrenergic blockers and their usefulness in
      CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled
      Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March,
      2011 and June, 2013 to August, 2015, and a number of studies identified. Results
      of those studies showed that use of beta-blockers was associated with decreased
      sudden cardiac death in patients with heart failure. However, contradictory
      results have also been reported. The present meta-analysis aimed to determine the
      efficacy of beta-blockers on mortality and morbidity in patients with heart
      failure. The results showed that mortality was significantly reduced by beta
      blocker treatment prior to the surgery of heart failure patients. The results
      from the meta-analysis studies showed that beta-blocker treatment in heart
      failure patients correlated with a significant decrease in long-term mortality,
      even in patients that meet one or more exclusion criteria of the MERIT-HF study.
      In summary, the findings of the current meta-analysis revealed beneficial effects
      different beta-blockers have on patients with heart failure or related heart
      disease.

PMID- 27703507
TI  - Association between insulin resistance and estrogen in sexual precocity of obese
      children.
AB  - The aim of the study was to examine the association between sexual precocity and
      high-molecular weight (HMW)-adiponectin and investigate the correlation of
      insulin resistance and estrogen levels in obese children. In total, 60 obese
      children (30 boys and 30 girls) with sexual precocity were included in group A,
      60 obese children (30 boys and 30 girls) without sexual precocity were included
      in group B, and 60 average weight children (30 boys and 30 girls) were included
      in group C. The levels of HMW adiponectin, fasting blood glucose, fasting
      insulin, luteinizing hormone (LH) peak, estradiol and testosterone were measured.
      The results showed that the HMW-adiponectin level of group A was the lowest and
      that of group C was the highest. The difference was statistically significant
      (P<0.05). The homeostasis model assessment of insulin resistance (HOMA-IR) and
      estradiol levels of group A were significantly higher than those of group B, and
      group B was higher than that of group C. LH peak and testosterone levels of group
      A were the lowest while those of group C were the highest. The differences were
      statistically significant (P<0.05). A subgroup analysis showed that the above
      results were more significant in girls. The Pearson correlation analysis revealed
      that the level of HMW-adiponectin was negatively correlated with HOMA-IR and
      estradiol (P<0.05), and positively correlated with the LH peak (P<0.05). In
      conclusion, sexual precocity of obese children may be associated with insulin
      resistance, and the link may be HMW-adiponectin.

PMID- 27703508
TI  - Diffusion tensor imaging of occult injury of optic radiation following optic
      neuritis in multiple sclerosis.
AB  - Multiple sclerosis (MS) is easily detected by routine magnetic resonance imaging
      (MRI). However, it is not possible to detect early or occult lesions in MS by
      routine MRI, and this may explain the inconsistency between the severity of the
      lesions found by MRI and the degree of clinical disability of patients with MS.
      The present study included 10 patients with relapsing-remitting MS and 10 healthy
      volunteers. Each patient underwent routine 3.0 T MRI, diffusion tensor imaging
      (DTI), and diffusion tensor tractography (DTT). Optic nerve and optic radiation
      were analyzed by DTI and DTT. The fractional anisotropy (FA), mean diffusivity
      (MD), lambda//, and lambda? values were measured. In the 10 patients with MS, 7
      optic nerves were affected, and 13 optic nerves were not affected. Cranial MRI
      showed that optic nerve thickening and hyperintensity occurred in 2 patients with
      MS. In the directionally encoded color maps, a hypointensive green signal in the
      optic nerve was observed in 3 patients with MS. The FA values were significantly
      lower and the MD, lambda//, and lambda? values were significantly higher in the
      affected and unaffected optic nerves and optic radiations in patients with MS in
      comparison with controls (P<0.05). There were no significant differences in these
      values between the affected and unaffected optic nerves and optic radiation in
      patients with MS (P>0.05). Diffusion tensor imaging is sensitive in the detection
      of occult injury of the optic nerve and optic radiation following optic neuritis.
      Diffusion tensor imaging may be a useful tool for the early diagnosis, treatment
      and management of MS.

PMID- 27703509
TI  - Influence of random urine albumin-creatinine ratio of pregnant women with
      hypertension during the gestation period on perinatal outcome.
AB  - The aim of the present study was to investigate the influence of the random urine
      albumin-creatinine ratio (ACR) of pregnant women with hypertension during the
      gestation period on perinatal outcome. A total of 6,758 pregnant women with
      pregnancy-induced hypertension and proteinuria were randomly selected between
      September, 2009 and June, 2015 for the study. Kidney function, blood pressure,
      history of gravidity and parity, embryo number and the birth weight of the
      participants was determined. Logistic regression and paired data correlation
      analyses were carried out with kidney function, blood pressure, history of
      gravidity and parity, embryo number, birth weight, maternal age, labor
      presentation and other risk factors as the independent variables and the newborn
      APGAR score as the dependent variable. The results showed that random urine ACR
      was increased and negatively correlated with the APGAR score (OR=-0.095,
      P=0.017). In conclusion, the increased random urine ACR can influence the
      postpartum outcome. Early intervention of women of childbearing age in early
      pregnancy or before pregnancy can minimize the adverse complications of infants
      and mothers such as pregnancy hypertension syndrome, and improve the outcome of
      the pregnancy.

PMID- 27703510
TI  - Ginsenoside Rb1 protects the intestinal mucosal barrier following peritoneal air
      exposure.
AB  - Ginsenoside Rb1 (GRb1), which is one of the main ingredients derived from Panax
      ginseng, has been widely used to treat various gastrointestinal disorders. The
      present study aimed to determine whether GRb1 was able to prevent intestinal
      mucosal barrier damage in rats following peritoneal air exposure for 3 h. GRb1
      (5, 10, and 20 mg/kg) was orally administrated via gavage four times prior to and
      following surgery. Blood and terminal ileum were sampled 24 h following surgery.
      Levels of serum D-lactate (D-LA) were detected using an enzyme-linked
      immunosorbent assay kit. Intestinal permeability was assessed by determining the
      intestinal clearance of fluorescein isothiocyanate-dextran (FD4). Activity of
      intestinal myeloperoxidase was measured to assess intestinal inflammation, and
      intestinal histopathology was assessed by light microscopy. The results showed
      that GRb1 reduced the level of serum D-LA, intestinal clearance of FD4, and the
      activity of intestinal myeloperoxidase. Intestinal edema and inflammation were
      also ameliorated by GRb1, and the Chiu's scores employed for assessing intestinal
      mucosal damage were also reduced in the GRb1-treated peritoneal air exposure
      group. In addition, GRb1 induced a significant difference at 10 and 20 mg/kg,
      indicating a dose-dependent effect. The results of the present study suggest that
      GRb1 may be able to protect the intestinal mucosal barrier against damage induced
      by peritoneal air exposure, which may be associated with its anti-inflammatory
      action.

PMID- 27703511
TI  - Effect of systemic injection of heterogenous and homogenous opioids on peripheral
      cellular immune response in rats with bone cancer pain: A comparative study.
AB  - Exogenous and endogenous opioids have been shown to modulate the immune system.
      Morphine-induced immunosuppression has been investigated extensively. However,
      the immune-regulating function of endogenous opioid peptides is unclear. The
      present study aimed to evaluate the difference in effects on cellular immune
      function between recombinant rat beta-endorphin (beta-EP; 50 ug/kg) and plant
      source morphine (10 mg/kg) via intraperitoneal injection treatment in a rat model
      of bone cancer pain. Walker 256 cells were injected into a tibial cavity
      injection to establish the bone cancer pain model. The paw withdrawal thresholds
      and body weights were measured prior to surgery, at 6 days after surgery, and
      following 1, 3,6 and 8 treatments. The spleen cells were harvested for detection
      of T cell proliferation, natural killer (NK) cell cytotoxicity, and the relative
      quantities of T cell subtypes (CD3+, CD4+ and CD8+ cells). Plasma levels of
      interleukin-2 (IL-2) were also determined. It was found that single or multiple
      treatments with beta-EP (a homogenous opioid peptide) and morphine (a
      heterogenous opioid) had good analgesic effects on bone cancer pain, while the
      analgesia provided by morphine was stronger than that of beta-EP. Treatment with
      beta-EP 3, 6 and 8 times increased the body weight gain in the rat model of bone
      cancer pain, while morphine treatment had on effect on it. With regard to
      immunomodulatory functions, beta-EP treatment increased T cell proliferation and
      NK cell cytotoxicity, and increased the relative quantities of T cell subtypes,
      but no effect on T cell secretion. However, morphine treatment decreased T cell
      proliferation and the levels of T cell subtypes. These data indicate that opioids
      from different sources have different effects on cellular immune function in
      vivo. A small dose of homogenous opioid peptide exhibited positive effects
      (analgesia and immune enhancement) on cancer pain. These results provide
      experimental evidence supporting the exploitation of human opioids for the
      treatment of cancer pain.

PMID- 27703512
TI  - Expression of Toll-like receptor 4 in lungs of immune-suppressed rat with
      Acinetobacter baumannii infection.
AB  - Toll-like receptor 4 (TLR4) is involved in the regulation of host responses to
      Acinetobacter baumannii (A. baumannii). The aim of the present study was to
      examine the function of TLR4 in lung inflammation in immune-suppressed rats with
      A. baumannii infection. A total of 72 Sprague-Dawley male rats were randomly
      divided into the control, A. baumannii infection and immune-suppressed infection
      groups. The immune-suppressed infection group was treated with 100 mg/kg
      hydrocortisone by subcutaneous injection every other day for 2 weeks prior to A.
      baumannii infection. Lung tissue was obtained on the 3rd and 7th day after
      tracheal inoculation with A. baumannii. The expression of TLR4 in bronchial and
      alveolar epithelial cells, and alveolar macrophage was examined using
      immunohistochemistry. The levels of interleukin (IL)-6, tumor necrosis factor
      (TNF)-alpha in bronchoalveolar lavage fluid were detected using ELISA. The
      results showed that in the control group, the expression of TLR4 was upregulated
      in the bronchial and alveolar epithelial, and alveolar macrophages, and the
      levels of IL-6 and TNF-alpha were increased in the early phase of A. baumannii
      infection. On the 7th day, no significant difference in the levels of IL-6 and
      TNF-alpha was observed between the A. baumannii infection and control groups.
      Conversely, the expression of TLR4 was downregulated in the immune-suppressed
      group, and the levels of IL-6 and TNF-alpha were reduced on the 3rd day after
      infection. In the subsequent observation period, the expression of TLR4 was
      upregulated and the levels of IL-6 and TNF-alpha were increased. In conclusion,
      the results show a critical role of TLR4 in mediating effective immune response
      in the lung of rat with A. baumannii infection.

PMID- 27703513
TI  - Clinical characteristics of drug-induced liver injury and related risk factors.
AB  - Drug-induced liver injury (DILI) is often undiagnosed or misdiagnosed clinically
      because of diagnostic difficulties caused by lack of laboratory-specific
      serological markers. In this study, we comprehensively assessed the clinical
      characteristics, laboratory indices, hepatotoxic drugs, risk factors and outcomes
      concerning DILI, and explored the similarities in mechanisms between Chinese and
      Western drug-induced DILI. Patients with a first diagnosis of DILI and a Roussel
      Uclaf Causality Assessment Method (RUCAM) score >3 points were enrolled for
      systematic retrospective study. Their clinical characteristics, clinical
      classification, risk factors, laboratory indices, hepatotoxic drugs and outcomes
      were analyzed. Cholestatic patients had the highest alkaline phosphatase (ALP)
      and prothrombin time activity (PTA) levels (P<0.05). Patients with medication
      time >=30 days had significantly higher positive rate of autoantibodies than
      those with medication time <30 days. Odds ratio values for DILI-related factors
      such as hepatobiliary diseases, immune dysfunction, diabetes, hypertension,
      chronic alcohol consumption and age >=45 years were 6.552, 6.130, 3.774, 2.801,
      2.002 and 1.838, respectively. Pathogeneses of Chinese and Western drug-induced
      DILI may be substantially the same. DILI accompanied with autoantibody positivity
      may indicate severe liver injury outcome. Hepatobiliary diseases, diabetes and
      hypertension are likely to increase drug susceptibility, and more prone to cause
      liver injury.

PMID- 27703514
TI  - Association between socioeconomic status and oral health behaviors: The 2008-2010
      Korea national health and nutrition examination survey.
AB  - Socioeconomic status (SES) has been reported to be associated with oral health
      behavior. Therefore, the present study was conducted to assess the relationship
      between SES and oral health behaviors in a large sample of the Korean population.
      Data from the Korea National Health and Nutrition Examination Survey, which was
      conducted between 2008 and 2010 by the Division of Chronic Disease Surveillance
      under the Korea Centers for Disease Control and Prevention and the Korean
      Ministry of Health and Welfare, were used in the present study. Daily tooth
      brushing frequency and the use of secondary oral products according to
      demographic variables and anthropometric characteristics of the participants were
      assessed. Multivariate logistic regression analyses were used to analyze the
      associations between daily tooth brushing frequency and the use of secondary oral
      products, and SES, urban/rural residence, body mass index (BMI), alcohol intake
      and smoking. An association between SES and tooth brushing frequency and the use
      of secondary oral products was detected after adjustment. Following adjustment
      for age, gender, BMI, smoking, drinking, exercise, energy intake, fat intake,
      periodontal treatment needs and education or income, the adjusted odds ratios and
      95% confidence intervals (CI) of tooth brushing >=3 per day in the highest income
      group were 1.264 (95% CI, 1.094-1.460) and 2.686 (95% CI, 2.286-3.155) for
      highest education level group. The adjusted odds ratios for the use of secondary
      oral products in the highest income and highest education groups were 1.835 (95%
      CI, 1.559-2.161) and 5.736 (95% CI, 4.734-6.951), respectively, after adjustment
      for age, gender, smoking, BMI, exercise, calorie intake, periodontal treatment
      requirements or income. The present study demonstrated an association between SES
      and oral health behaviors in a large sample of the Korean population. Within the
      limits of the present study, income and education were suggested as potential
      risk indicators for oral health behaviors; therefore, patients with a low SES
      should be investigated further, in relation to oral health.

PMID- 27703515
TI  - Screening and identification of microRNA involved in unstable angina using gene
      chip analysis.
AB  - Increasing evidence has suggested that microRNA (miRNA) may play a role in the
      pathogenesis of cardiovascular disease, which has led to a greater understanding
      of the complex pathophysiological processes underlying unstable angina (UA). The
      present study aimed to investigate changes in the miRNA expression profiles of
      patients with UA using gene-chip analysis, in order to further elucidate the
      pathogenesis of UA. Total RNA was extracted and purified from plasma samples
      collected from patients with UA and healthy controls. The samples underwent
      microarray analysis using an Exiqon miRCURY LNATM microRNA Array. Differentially
      expressed miRNAs were identified by volcano plot filtering, and were validated
      using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In
      addition, functional annotation of the differentially expressed miRNAs involved
      gene ontology analyses. Among the 212 miRNAs differentially expressed between the
      two groups, 82 were upregulated and 130 were downregulated. Notably, the results
      of the RT-qPCR were consistent with the gene-chip results. The miRNAs identified
      in the present study may be potential novel biomarkers for the prevention and
      early diagnosis of UA. Furthermore, the results of the present study suggested
      that UA occurs as a result of complex and dynamic processes regulated by numerous
      factors, including multiple miRNAs.

PMID- 27703516
TI  - Shikonin inhibits inflammation and chondrocyte apoptosis by regulation of the
      PI3K/Akt signaling pathway in a rat model of osteoarthritis.
AB  - Shikonin has previously been shown to have antitumor, anti-inflammatory,
      antiviral and extensive pharmacological effects. The aim of the present study was
      to explore whether the protective effect of shikonin is mediated via the
      inhibition of inflammation and chondrocyte apoptosis, and to elucidate the
      potential molecular mechanisms in a rat model of osteoarthritis. A model of
      osteoarthritis was established in healthy male Sprague-Dawley rats and 10
      mg/kg/day shikonin was administered intraperitoneally for 4 days. It was found
      that shikonin treatment significantly inhibited inflammatory reactions in the
      rats with osteoarthritis. Osteoarthritis was found to significantly increase
      interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and inducible nitric
      oxide synthase (iNOS) levels compared with those in the sham group. However,
      shikonin treatment significantly inhibited the increases in IL-1beta, TNF-alpha
      and iNOS levels in the rats with osteoarthritis. Furthermore, caspase-3 activity
      and cyclooxygenase (COX)-2 protein expression were significantly increased and
      phosphorylated Akt protein expression was greatly suppressed in rats with
      osteoarthritis when compared with the sham group. Shikonin administration
      attenuated the changes in caspase-3 activity and COX-2 expression and Akt
      phosphorylation in rats with osteoarthritis. These results indicate that shikonin
      inhibits inflammation and chondrocyte apoptosis by regulating the
      phosphoinositide 3-kinase/Akt signaling pathway in a rat model of osteoarthritis.

PMID- 27703517
TI  - FOXP3+ associated with the pro-inflammatory regulatory T and T helper 17 effector
      cells in asthma patients.
AB  - Asthma is a chronic bronchial inflammation that results to reversible incidence
      of airway obstruction and shortness of breath. Under normal circumstances, the
      lung immune system is maintained in a state of controlled inflammation, where
      balance exists between protective immunity mediated by effector cells and
      tolerance mediated by cells with regulatory function. Therefore, the inflammation
      observed in asthma patients may be caused by an imbalance between regulatory T
      (Treg) cells (CD4-positive with high expression of CD25 surface markers) and
      forkhead box P3 (FOXP3)-positive pro-inflammatory T helper 17 (Th17) cells. The
      aim of the present study was to evaluate whether reduced Treg cells and increased
      Th17 cells could be observed in the peripheral blood samples of asthma patients.
      As important markers of Treg cells, the expression levels of FOXP3 and
      interleukin (IL)-17a were analyzed via reverse trancription-quantitative
      polymerase chain reaction. The results indicated that the levels of cytokines
      that promote Th17 cells, including IL-6, IL-23 and TGF-beta, were found to
      increase in the bronchoalveolar lavage fluid sample of asthma patients. However,
      the IL-10 level in the corresponding sample was much lower compared with that in
      control individuals. In conclusion, these results suggest that asthma associated
      with a reduced proportion of Treg and Th17 cells in the blood is characterized by
      the expression of pro-inflammatory cytokines that may be beneficial for the
      continuous generation of Th17 cells.

PMID- 27703518
TI  - Gemstone spectral imaging for measuring adult bone mineral density.
AB  - The present study aimed to detect the bone Ca2+ content of L3 vertebrae in adults
      by gemstone spectral computed tomography. In total, 235 patients were selected
      and divided into age groups of 10 years each. The scanning data were used to
      detect the water-based and Ca2+-based substance levels on the L3 vertebral
      cancellous bone images. The results indicated that there were significant
      differences in vertebral Ca2+-water and water-Ca2+ densities determined by
      gemstone spectral imaging (GSI) between males and females in subjects aged 50-59
      years, 60-69 years, 70-79 years and >=80 years (P<0.05). The ages of male and
      female participants were negatively correlated with vertebral Ca2+-water density
      (P<0.01) and water-Ca2+ density (P<0.01). In conclusion, GSI may be used as a
      novel method of measuring the vertebral adult bone mineral density.

PMID- 27703520
TI  - Thermal ablation in cancer.
AB  - Radiofrequency ablation (RFA) and cryoablation are alternative forms of therapy
      used widely in various pathological states, including treatment of
      carcinogenesis. The reason is that ablation techniques have ability of modulating
      the immune system. Furthermore, recent studies have applied this form of therapy
      on tumor microenvironment and in the systematic circulation. Moreover, RFA and
      cryoablation result in an inflammatory immune response along with tissue
      disruption. Evidence has demonstrated that these procedures affect carcinogenesis
      by causing a significant local inflammatory response leading to an immunogenic
      gene signature. The present review enlightens the current view of these
      techniques in cancer.

PMID- 27703519
TI  - Re-irradiation alternatives for recurrent high-grade glioma.
AB  - Despite advances in the fields of surgery, chemotherapy and radiotherapy, the
      prognosis for high-grade glioma (HGG) remains unsatisfactory. The majority of HGG
      patients experience disease recurrence. To date, no standard treatments have been
      established for recurrent HGG. Repeat surgery and chemotherapy demonstrate
      moderate efficacy. As recurrent lesions are usually located within the previously
      irradiated field, a second course of irradiation was once considered
      controversial, as it was considered to exhibit unsatisfactory efficacy and
      radiation-related toxicities. However, an increasing number of studies have
      indicated that re-irradiation may present an efficacious treatment for recurrent
      HGG. Re-irradiation may be delivered via conventionally fractionated stereotactic
      radiotherapy, hypofractionated stereotactic radiation therapy, stereotactic
      radiosurgery and brachytherapy techniques. In the present review, the current
      literature regarding re-irradiation treatment for recurrent HGG is summarized
      with regard to survival outcome and side effects.

PMID- 27703521
TI  - Caveolin-1 is overexpressed in hypopharyngeal squamous cell carcinoma and
      correlates with clinical parameters.
AB  - The present study aimed to identify the role of caveolin-1 (CAV1) in
      hypopharyngeal squamous cell carcinoma (HSCC) and identify its possible
      correlation with tumor clinical parameters. Expression of CAV1 was measured using
      immunohistochemical staining of 66 HSCC samples and 44 samples from
      morphologically normal tissues adjacent to the carcinomas. Expression of CAV1 in
      HSCC and paracancerous tissues were 71.2 and 9.5% respectively. Levels of CAV1
      expression were significantly associated with tumor differentiation, tumor-node
      metastasis stage and lymph nodes metastasis (P<0.05). The present study
      identified that expression of CAV1 in HSCC is significantly higher than in
      paracancerous tissues, suggesting that this high expression of CAV1 is associated
      with tumor invasion and metastasis.

PMID- 27703522
TI  - SREBP-1 is an independent prognostic marker and promotes invasion and migration
      in breast cancer.
AB  - Re-programming of lipogenic signaling has been previously demonstrated to result
      in significant alterations in tumor cell pathology. Sterol regulatory element
      binding protein 1 (SREBP-1) is a known transcription factor of lipogenic genes.
      Despite the fact that its functions in proliferation and apoptosis have been
      elucidated in recent studies, its role in tumor cell migration and invasion,
      particularly in breast cancer, remains unclear. In present study, the messenger
      RNA and protein expression levels of SREBP-1 in cancer tissues were observed to
      be overexpressed compared with those in matched para-cancerous tissues (P<0.01).
      SREBP-1 level was highly positively correlated with tumor differentiation
      (P<0.001), tumor-node-metastasis stage (P=0.044) and lymph node metastasis
      (P<0.001). High expression of SREBP-1 predicted poor prognosis in patients with
      breast cancer. Additionally, multivariate analysis revealed that SREBP-1 was an
      independent factor of 5-year overall and disease-specific survival in breast
      cancer patients (P<0.01). In vitro studies revealed that the suppression of SREBP
      1 expression in both MDA-MB-231 and MCF7 cells significantly inhibited cell
      migration and invasion (P<0.01). The present data indicate that SREBP-1 plays a
      critical role in breast cancer migration and invasion, and may serve as a
      prognostic marker of this malignancy.

PMID- 27703523
TI  - Mean platelet volume provides beneficial diagnostic and prognostic information
      for patients with resectable gastric cancer.
AB  - Gastric cancer is the fourth most frequent cancer and the second cause of cancer
      related mortalities worldwide. Platelets play an important and multifaceted role
      in cancer progression. Elevated mean platelet volume (MPV) detected in peripheral
      blood has been identified in various types of cancer. In the present study, we
      investigated the application value of MPV in early diagnostic and prognostic
      prediction in patients with resectable gastric cancer. In total, 168 patients
      with resectable gastric cancer were included and separated into the gastric
      cancer and healthy control groups according to median pre-operatic MPV value (MPV
      low, <10.51 or MPV high, >=10.51). The results showed that the pre-operatic MPV
      level was significantly higher in gastric cancer patients compared with the
      healthy subjects. Low pre-operatic MPV level correlated with improved
      clinicopathological features, including decreased depth of invasion, less
      lymphonodus metastasis and early tumor stage. The Kaplan-Meier plots showed that
      the patients with higher pre-operatic MPV had decreased overall survival (OS) and
      disease-free survival (DFS). Surgical tumor resection resulted in a significant
      decrease in the MPV level. The patients whose MPV level decreased following
      surgery had an improved OS. Multivariate Cox regression analysis revealed that
      the depth of invasion, lymphonodus metastasis, American Joint Committee on Cancer
      (AJCC) stage, and changes in MPV following surgery were prognostic factors
      affecting OS, and the AJCC stage and pre-operatic MPV were prognostic factors
      affecting DFS. In conclusion, MPV measurement can provide important diagnostic
      and prognostic results in patients with resectable gastric cancer.

PMID- 27703525
TI  - Novel recombinant protein FlaA N/C increases tumor radiosensitivity via NF-kappaB
      signaling in murine breast cancer cells.
AB  - The recombinant protein flagellin A (FlaA) N/C, derived from the flagellin
      protein of Legionella pneumophila, has been shown to increase the expression of
      cytoprotective cytokines, activate the nuclear factor-kappaB (NF-kappaB)
      signaling pathway, and increase the survival of mice following total body
      irradiation. Determi ning whether FlaA N/C has a sensitizing effect on tumor
      radiation or a direct tumoricidal effect is critical for its application as an
      effective radiation protection agent. The present study investigated the
      molecular mechanism underlying the tumor radiosensitivity of FlaA N/C. FlaA N/C
      was found to increase tumor apoptosis and autophagy, regulate the cell cycle and
      increase radiosensitivity in 4T1 tumor cells. Furthermore, FlaA N/C was found to
      promote radiosensitivity by activating NF-kappaB signaling. Finally, the present
      study analyzed FlaA N/C-enhanced radiosensitivity in animal models, and FlaA N/C
      was found to significantly prolong the survival period of mice after total body
      radiation. This indicates that FlaA N/C might be a novel radiation sensitizer in
      tumor radiation therapy.

PMID- 27703524
TI  - Methylation pattern of CDH1 promoter and its association with CDH1 gene
      expression in cytological cervical specimens.
AB  - Cervical cancer is the fourth leading cause of cancer mortality in females
      worldwide. Infection with high-risk human papillomavirus (HPV) is essential but
      insufficient to cause cervical cancer, and the clearance of HPV infection is
      mediated by the immune system. The deficit of molecules responsible for adhesion
      may play a role in the development of cervical cancer. E-cadherin is encoded by
      the cadherin 1 (CDH1) gene, and is involved in cell adhesion by forming adherens
      junctions. The aim of present study was to investigate the methylation pattern of
      the CDH1 promoter and to identify the association between CDH1 promoter
      hypermethylation, CDH1 gene expression and HPV infection in cervical specimens
      obtained from 93 patients with low-grade squamous intraepithelial lesions (SILs),
      high-grade SILs or squamous cell carcinomas, and from 47 patients with normal
      cervical cytology (HPV-negative). The methylation pattern of the CDH1 promoter
      was investigated by methylation-specific polymerase chain reaction and
      quantitative pyrosequencing. CDH1 gene expression was measured by relative
      quantification. CDH1 methylation was significantly higher in both types of
      lesions and in cervical cancer than in normal samples, and CDH1 gene expression
      was significantly reduced during SIL progression (P=0.0162). However, the
      influence of HPV infection or HPV E6 expression on the methylation pattern of the
      CDH1 gene or its gene expression levels could not be confirmed. The present
      results support that the methylation of the CDH1 gene is age-related in patients
      with cervical lesions (P=0.01085), and therefore, older patients could be more
      susceptible to cancer than younger patients. The important methylation of the
      CDH1 promoter occurred near the transcription factor binding sites on nucleotides
      -13 and +103, which are close to the translational start codon. These results
      suggest that methylation at these sites may be an important event in the
      transcriptional regulation of E-cadherin, and in patients harboring these
      methylated cytosines, this event may facilitate HPV-driven carcinogenesis.

PMID- 27703526
TI  - Ki-67 is overexpressed in human laryngeal carcinoma and contributes to the
      proliferation of HEp2 cells.
AB  - Ki-67 is one of the most useful markers to evaluate cell proliferative activity
      and has been widely used in tumor treatment and research. However, its role in
      human laryngeal carcinoma remains poorly defined. The aim of the present study
      was to investigate the expression of Ki-67 in human laryngeal squamous carcinoma
      and the effect of Ki-67 gene silencing by small interfering (si)RNA on the
      proliferation of human laryngocarcinoma HEp2 cells. Immunohistochemistry and
      reverse transcription-quantitative polymerase chain reaction were performed to
      examine the expression of Ki-67 in human laryngeal squamous carcinoma tissues and
      adjacent non-cancer tissues from 50 patients with laryngeal squamous carcinoma.
      RNA interference was used to knock down the expression of Ki-67 in the HEp2 cell
      line, and the proliferation of the treated cells was observed in vitro. Western
      blot analysis was used to determine the expression levels of epidermal growth
      factor receptor (EGFR) and E-cadherin in the treated cells. The expression of Ki
      67 in the laryngeal squamous carcinoma tissues was significantly higher than that
      of the adjacent non-tumor tissues (P=0.028). The high expression of Ki-67 in
      cancer was significantly correlated with cervical lymph node metastasis and
      clinical outcomes (all P<0.001). The silencing of Ki-67 resulted in the
      inhibition of proliferation of the HEp2 human laryngocarcinoma cells (P<0.001).
      In addition, compared with the control group, the expression levels of EGFR and E
      cadherin in the Ki-67 siRNA-treated cells were significantly decreased (P<0.001)
      and increased (P<0.001), respectively. These results suggested that Ki-67 is
      important in regulating the proliferation of human laryngocarcinoma HEp2 cells
      and that the mechanism may at least partially be associated with the upregulation
      of EGFR and the downregulation of E-cadherin. Overall, Ki-67 can be used as an
      important indicator for judging clinical progress and estimating prognosis in
      human laryngeal squamous carcinoma.

PMID- 27703527
TI  - V8 induces apoptosis and the endoplasmic reticulum stress response in human
      multiple myeloma RPMI 8226 cells via the PERK-eIF2alpha-ATF4 signaling pathway.
AB  - Multiple myeloma (MM) is a fatal hematological cancer characterized by clonal
      plasma cell proliferation in the bone marrow. MM has an increasing global
      incidence and a poor prognosis. There are limited treatment options available for
      MM, and this is further compounded by the development of drug resistance. The
      present study demonstrated that 7-{4-[Bis-(2-hydroxyethyl)-amino]-butoxy}-5
      hydroxy-8-methoxy-2-phenylchromen-4-one (V8), a novel synthetic flavonoid,
      induced apoptosis in human MM RPMI 8226 cells in a dose- and time-dependent
      manner, using cell viability assays and flow cytometry. Subsequently, V8-induced
      apoptosis in RPMI 8226 cells was revealed to occur via mitochondria-mediated
      pathways. The activity of caspase-3, -8 and -9, and the mRNA level of B-cell
      lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large were greatly increased, while
      the expression of Bcl-2-like protein 4 and BH3 interacting domain death agonist
      was significantly decreased in RPMI 8226 cells following V8 treatment, as
      observed using quantitative polymerase chain reaction (qPCR). In addition,
      western blotting revealed that the release of mitochondrial cytochrome c into the
      cytosol was promoted by V8. Furthermore, a clear alteration in endoplasmic
      reticulum (ER) stress was observed in cells treated with V8; upregulation of
      glucose-regulated protein (GRP) 78, GRP94, C/EBP homologous protein, cleavage of
      caspase-12, phosphorylated protein kinase RNA-like endoplasmic reticulum kinase
      (p-PERK), phosphorylated eukaryotic initiation factor 2alpha (p-eIF2alpha) and
      activating transcription factor 4 (ATF4) was observed with qPCR and western
      blotting, suggesting that V8-induced apoptosis is involved in the ER stress
      response. Overall, the present results demonstrated that V8 induced apoptosis in
      human MM RPMI 8226 cells via the PERK-eIF2alpha-ATF4 ER stress response pathway,
      which may provide novel directions for exploiting this compound as a potential
      anti-neoplastic drug for MM therapy.

PMID- 27703528
TI  - Molecular expression of vascular endothelial growth factor, prokineticin receptor
      1 and other biomarkers in infiltrating canalicular carcinoma of the breast.
AB  - Vascular endothelial growth factor (VEGF) is important in the growth and
      metastasis of cancer cells. In 2001, another angiogenic factor, endocrine gland
      derived VEGF (EG-VEGF), was characterized and sequenced. EG-VEGF activity appears
      to be restricted to endothelial cells derived from endocrine glands. At the
      molecular level, its expression is regulated by hypoxia and steroid hormones.
      Although VEGF and EG-VEGF are structurally different, they function in a
      coordinated fashion. Since the majority of mammary tumors are hormone-dependent,
      it was hypothesized that EG-VEGF would be expressed in these tumors, and
      therefore, represent a potential target for anti-angiogenic therapy. The aim of
      the present study was to assess the expression of VEGF, EG-VEGF and its receptor
      (prokineticin receptor-1), as well as that of breast cancer resistant protein,
      estrogen receptor, progesterone receptor and human epidermal growth factor
      receptor 2, in 50 breast samples of infiltrating canalicular carcinoma (ICC) and
      their correlation with tumor staging. The samples were analyzed using reverse
      transcription-quantitative polymerase chain reaction and immunohistochemistry.
      Both angiogenic growth factors were identified in all samples. However, in 90% of
      the samples, the expression level of VEGF was significantly higher than that of
      EG-VEGF (P=0.024). There was no association between the expression of VEGF, EG
      VEGF or its receptor with tumor stage. In ICC, the predominant angiogenic factor
      expressed was VEGF. The expression level of either factor was not correlated with
      the tumor-node-metastasis stage. Although ICC is derived from endothelial cells,
      EG-VEGF expression was not the predominant angiogenic/growth factor in ICC.

PMID- 27703529
TI  - Rescuing defective tumor-infiltrating T-cell proliferation in glioblastoma
      patients.
AB  - Primary glioblastoma (GBM) is the most prevalent brain cancer, with fast
      progression and a poor prognosis. Current treatment options are unable to fully
      manage GBM since it is highly resistant to radiation and chemotherapy, and it
      cannot be completely removed by surgery. Thus, immunotherapeutic strategies
      utilizing tumor-infiltrating T cells have been investigated. In the present
      study, the T-cell response in GBM patients was examined in resected tumor samples
      and peripheral blood samples by flow cytometry. It was found that tumor
      infiltrating T cells represented a rare population in all tumor cells, and were
      more refractory to anti-cluster of differentiation 3 (CD3) stimulation than their
      peripheral blood counterparts. A number of strategies were then assessed to boost
      tumor-infiltrating T-cell proliferation, and it was found that pre-incubation
      with 20 U/ml interleukin (IL)-2, as well as sequestration of IL-10 in culture,
      improved tumor T-cell proliferation following anti-CD3 stimulation. The
      stimulation of blood antigen-presenting cells by lipopolysaccharide, however, did
      not improve tumor T-cell proliferation. Overall, the present results provided a
      viable strategy for improving tumor-infiltrating CD3+ T-cell responses in GBM
      patients.

PMID- 27703530
TI  - Contrary melanoma-associated antigen-A expression at the tumor front and center:
      A comparative analysis of stage I and IV head and neck squamous cell carcinoma.
AB  - There is a growing body of evidence indicating that several melanoma-associated
      antigen-A (MAGE-A) subgroups contribute to the malignancy of head and neck
      cancer. The present study retrospectively analyzed the expression of all known
      MAGE-A subgroups in the tumor front and center of 38 head and neck cancer
      patients (Union for International Cancer Control stage I or IV) by
      immunohistochemistry. MAGE-A1, -A6, -A8, -A9 and -A11 were expressed at
      significantly higher levels at the tumor front of stage IV specimens compared
      with the tumor front of stage I specimens. In stage I cancer, the tumor center
      and front ratio (C/F ratio) for each subgroup was >1.0. In stage IV cancer, the
      C/F ratio was <1.0 in 9/11 subgroups. The most significant change in the
      expression pattern was observed for MAGE-A11. These results indicated that there
      is a marked alteration and shift to the invasive front of almost all MAGE-A
      subgroups, but particularly MAGE-A11, during the progression of head and neck
      squamous cell carcinoma.

PMID- 27703532
TI  - Overlap of the cancer genome atlas and the immune epitope database.
AB  - Mutant peptides resulting from cancer drivers or passenger mutations are expected
      to have the potential to serve as a basis for cancer vaccines. However, a number
      of parameters regulate vaccine-associated immunogenicity, including the
      suitability of a peptide for binding to an antigen-presenting molecule or
      antibody. In order to obtain a basic indication of the prospect of human cancer
      epitope identification via current database development strategies, an overlap of
      the mutant Homo sapiens epitopes listed on the Immune Epitope Database (IEDB) and
      the mutant peptides indicated by The Cancer Genome Atlas (TCGA) somatic mutation
      database was obtained. No putative TCGA mutant peptides were detected among the
      8,890 14-18 amino acid (AA) IEDB peptides available. In total, 3 IEDB mutant
      epitopes that encompassed a TCGA mutant AA position, but did not overlap the
      exact position of the TCGA mutant AA, were detected. The results of the present
      analysis confirm that verification of certain aspects of cancer epitope function
      can be obtained via the continued and systematic expansion of databases
      representing human protein epitopes. However, the analysis also indicates that
      there is relatively limited systematic information available regarding antigen
      presenting molecule epitopes and cancer-related mutant peptides.

PMID- 27703533
TI  - Solving medical mysteries: hidden stresses and unexplained symptoms.
AB  - Medically unexplained symptoms and chronic functional syndromes are common but
      few healthcare professionals have had formal training about their connection to
      psychosocial issues. A systematic approach to diagnosis and treatment based on
      experience with over 7000 of these patients is described. Outcomes improve with
      assessment for and treatment of current life stresses, the prolonged impact of
      adversity in childhood and somatic presentations of depression, post-traumatic
      stress, and anxiety disorders.

PMID- 27703531
TI  - Lithium chloride has a biphasic effect on prostate cancer stem cells and a
      proportional effect on midkine levels.
AB  - Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide
      and the levels of differentiation growth factor midkine (MK) are increased in
      PCa. Cancer and/or the treatment process itself may lead to psychiatric
      disorders. Lithium chloride (LiCl) has anti-manic properties and has been used in
      cancer therapy; however, it has a queried safety profile. In addition, cancer
      stem cells are responsible for the heterogeneous phenotype of tumor cells; they
      are involved in progression, metastasis, recurrence and therapy resistance in
      various cancer types. The aims of the present study were to investigate the
      effect of different concentrations of LiCl on PCa stem cells (whether a shift
      from tumorigenic to non-tumorigenic cells occurs) and to determine if these
      results can be explained through changes in MK levels. Monolayer and spheroid
      cultures of human prostate stem cells and non-stem cells were incubated with low
      (1, 10 uM) and high (100, 500 uM) concentrations of LiCl for 72 h. Cell
      proliferation, apoptotic indices, MK levels and ultrastructure were evaluated.
      Cells stimulated with low concentrations showed high proliferation, low apoptotic
      indices, high MK levels and more healthy ultrastructure. Opposite results were
      obtained at high concentrations. Furthermore, stem cells were more sensitive to
      stimulation and more resistant to inhibition than non-stem cells. LiCl exhibited
      concentration-dependent effects on stem cell and non-stem cell groups. MK levels
      were not involved in the biphasic effect of LiCl; however, they were
      proportionally affected. To the best of our knowledge, the present study was the
      first to show the effect of LiCl on PCa stem cells through MK.

PMID- 27703534
TI  - Patients' perception of differences in general practitioners' attitudes toward
      immigrants compared to the general population: Qualicopc Slovenia.
AB  - INTRODUCTION: Globally, the number of immigrants is rising every year, so that
      the number of immigrants worldwide is estimated at 200 million. In Slovenia,
      immigrants comprise 6.5% of the overall population. Immigrants bring along to a
      foreign country their cultural differences and these differences can affect
      immigrants' overall health status and lead to chronic health conditions. The aim
      of this study was to identify patients' perception of general practitioners'
      (GPs') attitudes toward immigrants in Slovenia. METHODS: This study was based on
      the Qualicopc questionnaire. We used the questions that targeted patients'
      experience with the appointment at their GP on the day that the study was carried
      out. RESULTS: There were no differences in GPs' accessibility based on groups
      included in our study (p>0.05). Compared to the non-immigrant population, first
      generation immigrants answered that their GPs were impolite (p=0.018) and that
      they did not take enough time for them (p=0.038). In addition, they also
      experienced more difficulties understanding their GP's instructions (p<0.001).
      Second-generation immigrants experienced more negative behaviour from GPs, and
      first-generation immigrants had more difficulties understanding GPs'
      instructions. CONCLUSION: There may be some differences in patients' perception
      of GPs' attitudes towards immigrants in comparison with the general Slovenian
      population. However, based on the perception of the immigrants that do benefit
      from the medical care it is not possible to judge the GPs' attitudes towards
      immigrants as worse compared to their attitude towards the non-immigrant
      population. Indeed, there may be other reasons why the patients answered the way
      they did.

PMID- 27703535
TI  - Cross-cultural adaptation and validation of the disease specific questionnaire
      OQLQ in Serbian patients with malocclusions.
AB  - INTRODUCTION: Dentofacial disorders may potentially significantly affect the
      quality of life. Objectives of this study were to validate translated and
      culturally adapted Orthognatic Quality of Life Questionnaire (OQLQ) on a cohort
      of Serbian patients with malocclusions. METHODS: The questionnaire was validated
      in 111 consecutive patients with malocclusions, seen between December 2014 and
      February 2015 at the Clinic of Orthodontics, Faculty of Dental Medicine,
      University of Belgrade. Clinical validity was assessed comparing the mean scores
      for the four subscales of the OQLQ and mean PAR pre-treatment score. In order to
      assess whether the allocation of items in the subscales corresponds to their
      distribution in the original questionnaire, an exploratory factor analysis
      (principal component analysis with varimax rotation) was conducted. RESULTS: The
      results of the internal consistency analysis demonstrated good relationships
      between the items; Cronbach's alpha coefficients for the four subscales were
      highly significant (p<0.001) (0.88-0.91). All items were significantly correlated
      between baseline and the retest (6 weeks after). The correlations between the PAR
      and all four domains of the OQLQ were all significant (p<0.01). The loading
      weights obtained in the exploratory factor analysis showed that this model
      revealed four factors with eigenvalue greater than 1, explaining the 64.0% of the
      cumulative variance. The majority of the items (86.4%) in the Serbian version of
      the OQLQ presented the highest loading weight in the subscales assigned by the
      OQLQ developer. CONCLUSIONS: The psychometric properties of the OQLQ (Serbian
      version) have exceptional internal consistency and reproducibility as an
      instrument for evaluation of dental malocclusions. Additionally, this
      questionnaire may be useful as a supplementary outcome measure in persons with
      malocclusions.

PMID- 27703536
TI  - Under-reporting of sexually transmitted infection with chlamydia trachomatis - a
      revision of surveillance system is required.
AB  - INTRODUCTION: To consider whether a revision of the national chlamydia
      surveillance system is needed, the objectives were to estimate the proportion of
      laboratory confirmed cases at the Institute of Microbiology and Immunology (IMI)
      not reported to the National Institute of Public Health (NIPH), and to assess the
      completeness of reporting for individual data items. METHODS: The dataset with
      information about the cases diagnosed at the IMI during 2007-2010, and the
      national chlamydia surveillance data at the NIPH, were linked using SOUNDEX code
      and the date of birth as unique identifier. The proportion of unreported cases
      was calculated. The proportions of records with missing data for individual
      variables were estimated for all reported cases during the same period. Chlamydia
      testing and reported rates for the period 2002-2010 were presented. RESULTS: Of
      576 laboratory confirmed chlamydia cases at the IMI during 2007-2010, 201 were
      reported to the NIPH, corresponding to 65.1% of the overall underreporting (50.4%
      among dermatovenerologists, 90.1% among gynaecologist and 100% among other
      specialists). Item response was above 99% for demographic variables and from 69%
      to 81% for sexual behaviour variables. Higher testing rates corresponded to
      higher diagnosed rates. CONCLUSIONS: Surveillance data underestimated diagnosed
      chlamydia infection rates. Mandatory reporting of cases by laboratories with less
      variables, including unique identifier, gender, date of diagnosis, and reporting
      physician specialty, together with numbers of tests performed (for estimating
      testing and positivity rates) would simplify the surveillance system and
      eliminate underreporting of laboratory confirmed cases, while still providing
      necessary information for public health policies.

PMID- 27703537
TI  - Quality of care for patients with diabetes mellitus type 2 in 'model practices'
      in Slovenia - first results.
AB  - BACKGROUND: A new organisation at the primary level, called model practices,
      introduces a 0.5 full-time equivalent nurse practitioner as a regular member of
      the team. Nurse practitioners are in charge of registers of chronic patients, and
      implement an active approach into medical care. Selected quality indicators
      define the quality of management. The majority of studies confirm the
      effectiveness of the extended team in the quality of care, which is similar or
      improved when compared to care performed by the physician alone. The aim of the
      study is to compare the quality of management of patients with diabetes mellitus
      type 2 before and after the introduction of model practices. METHODS: A cohort
      retrospective study was based on medical records from three practices. Process
      quality indicators, such as regularity of HbA1c measurement, blood pressure
      measurement, foot exam, referral to eye exam, performance of yearly laboratory
      tests and HbA1c level before and after the introduction of model practices were
      compared. RESULTS: The final sample consisted of 132 patients, whose diabetes
      care was exclusively performed at the primary care level. The process of care has
      significantly improved after the delivery of model practices. The most
      outstanding is the increase of foot exam and HbA1c testing. We could not prove
      better glycaemic control (p>0.1). Nevertheless, the proposed benchmark for the
      suggested quality process and outcome indicators were mostly exceeded in this
      cohort. CONCLUSION: The introduction of a nurse into the team improves the
      process quality of care. Benchmarks for quality indicators are obtainable. Better
      outcomes of care need further confirmation.

PMID- 27703538
TI  - Knowledge of health principles among professionals in Slovenian kindergartens.
AB  - OBJECTIVES: Preschool children have significant health issues. From the relevant
      legislation and regulations, it can be seen that kindergarten teachers (KTs) and
      kindergarten teacher assistants (KTAs) are expected to be familiarwith the basic
      hygienic measures and steps for preventing injuries and illnesses, to recognize
      infectious diseases, and to know how to give the first aid. To gain these skills,
      a continuous life-long learning is necessary, because the characteristics of
      diseases are changing. Study design: original research. METHODS: 45 kindergartens
      in Slovenia were randomly selected and a questionnaire with 17 questions on
      health themes was sent. An analysis was performed via SPSS 17.0, using
      descriptive methods and nonparametric chi2 tests. RESULTS: There were 774
      participants, of whom 56% were KTs and 44% KTAs. The share of KTs and KTAs who
      consider their knowledge of health principles to be very good or excellent is
      67%. Their estimation of first aid knowledge is lower. They are also well aware
      of the importance of health knowledge in their work; a total of 87% strongly
      agree with this. The results also show that they are familiar with hygiene
      principles. The chi2 test showed there are certain statistically characteristic
      connections between the age of teachers and their assistants, occupation and work
      experiences. CONCLUSIONS: Because children are a particularly vulnerable group,
      teachers can encounter injuries and sudden illnesses at their work. Supplementary
      education is necessary among skilled workers in educational institutions,
      including kindergartens.

PMID- 27703540
TI  - Prevalence of problematic internet use in Slovenia.
AB  - BACKGROUND: Internet use is an integral part of our everyday activities; however,
      Internet use may become problematic and harmful in a minority of cases. The
      majority of reported prevalence rates of problematic Internet use refer to
      adolescent samples, whereas epidemiological studies on representative adult
      populations are lacking. This study aimed to reveal the prevalence and
      characteristics of problematic Internet use in Slovenia. METHODS: Problematic
      Internet Use Questionnaire (PIUQ) was included in European Health Interview Study
      (EHIS) on representative Slovenian sample. The frequency of Internet use and
      problematic Internet use were both assessed. RESULTS: 59.9% of Slovenian adult
      population uses the Internet daily, and 3.1% are at risk of becoming problematic
      Internet users, 11% in the age group from 20 to 24 years. Those being at risk for
      becoming problematic Internet users are younger (mean age 31.3 vs. 48.3 for non
      problematic users), more likely to be males (3.6% of males, whereas 2.6% of
      females are affected), students (12.0%), unemployed (6.3%) or unable to work
      (8.7%), single (6.5%), with high education (4.5%). Regression analysis revealed
      that the strongest predictor of being at risk for problematic Internet use is age
      (beta=-0.338, p<0.001); followed by high educational level (beta=0.145; p<0.001)
      and student status (beta=0.136; p<0.001). CONCLUSION: 3.1% of Slovenian adult
      population are at risk of becoming problematic Internet users, whereas 3 out of
      20 Slovenian adolescents aged from 18 to 19 years are at risk (14.6%). Prevention
      programs and treatment for those affected are paramount, especially for the young
      generation.

PMID- 27703539
TI  - Analysis of expired medications in Serbian households.
AB  - INTRODUCTION: An ongoing issue of expired medications accumulating in some
      households is a universal problem around the world. The aim of the study was to
      investigate the extent and structure of expired medications in Serbian
      households, and to determine which therapeutic groups generated the most waste.
      METHODS: This was an observational, cross-sectional study conducted in households
      in the city of Novi Sad, Serbia. The study had been performed over 8 month period
      (December 2011 - July 2012) and it consisted of personal insights into the
      medication inventory in households. RESULTS: Of 1008 families, 383 agreed to
      participate and complete the questionnaire (38.3% response rate). In almost a
      half of households (44.4%), expired medications were maintained. The amount of
      expired medications was 402 items, corresponding to 9.2% of total medications
      presented in surveyed households. The majority of expired medications (64.7%) was
      in solid dosage (tablets, capsules, granules, lozenges), following semisolid
      (ointments, creams, gel, suppositories) and liquid dosage forms (drops, syrups).
      Expired medications in the households belonged mostly to 3 categories:
      antimicrobials for systemic use (16.7%), dermatological preparation (15.9%) and
      medications for alimentary tract and metabolism (14.2%). CONCLUSIONS: This study
      revealed that there were relatively large quantities of expired medications in
      Serbian households, with a high prevalence of antibiotics for systemic use, anti
      inflammatory and antirheumatic products, and medications for alimentary tract and
      metabolism.

PMID- 27703541
TI  - Prevalence of violence towards nursing staff in Slovenian nursing homes.
AB  - INTRODUCTION: The purpose of this research was to identify the prevalence of
      violence towards nursing staff in Slovenian nursing homes. METHODS: For the
      purpose of this study, a non-experimental sampling method was employed, using a
      structured questionnaire as a data collection instrument (n=527). The contents of
      the questionnaire proved valid and reliable, with a high enough degree of
      internal consistency (Cronbach Alpha minimum 0.82). RESULTS: The nursing staffs
      working in nursing homes for senior citizens are at high risk of violence. In the
      last year, the employees were most often faced with verbal violence (71.7%),
      physical violence (63.8%) and sexual violence (35.5%). 35.5% of employees
      suffered injuries at their working place. During aggressive outbursts of nursing
      home residents, employees particularly experience vulnerability, fear and
      insecurity. CONCLUSION: There is a need for a comprehensive approach to tackle
      workplace violence. Some psychiatric health care facilities have already
      introduced certain measures in this field, and reduction of workplace violence
      proves that it is possible to reduce aggressive outbursts of patients. After
      conducting further quantitative research, which would expose detailed
      characteristics and the background of such violence, it would be sensible to
      develop similar measures in the field of health care in nursing homes.

PMID- 27703543
TI  - Health care reforms.
AB  - In large systems, such as health care, reforms are underway constantly. The
      article presents a definition of health care reform and factors that influence
      its success. The factors being discussed range from knowledgeable personnel, the
      role of involvement of international experts and all stakeholders in the country,
      the importance of electoral mandate and governmental support, leadership and
      clear and transparent communication. The goals set need to be clear, and it is
      helpful to have good data and analytical support in the process. Despite all
      debates and experiences, it is impossible to clearly define the best approach to
      tackle health care reform due to a different configuration of governance
      structure, political will and state of the economy in a country.

PMID- 27703542
TI  - Primary care for the Roma in Europe: Position paper of the European forum for
      primary care.
AB  - Roma populations' low health status and limited access to health services,
      including primary care, has been documented in many European countries, and
      warrants specific health policies and practices. A variety of experiences shows
      how primary care can adjust its practices to reduce the barriers to primary care
      for Roma populations. At local level, establishing collaboration with Roma
      organisations helps primary care to improve mutual relations and quality of care.
      Mediation has proved to be an effective tool. Skills training of primary care
      practitioners may enhance their individual competences. Research and
      international sharing of experiences are further tools to improve primary care
      for the Roma people.

PMID- 27703544
TI  - Zika: an old virus with a new face.
AB  - Zika virus is a mosquito-borne flavivirus that represents a public health
      emergency at the ongoing epidemic. This obscure virus was limited to sporadic
      cases in Africa and Asia, until the emergence of Zika virus in Brazil in 2015,
      when it rapidly spread throughout the Americas. Most Zika virus infections are
      subclinical or characterized by mild febrile illness. However, neurological
      complications, including Guillain-Barre syndrome in adults, and congenital
      anomalies, including microcephaly in babies born to infected mothers, raised a
      grave concern. Currently, there is no specific antiviral treatment or vaccine
      available for Zika virus infection. Thus, international public health response is
      primarily focused on preventing infection, particularly in pregnant women, and on
      providing up-to-date recommendations to reduce the risk of non-vector
      transmission of Zika virus.

PMID- 27703546
TI  - The prevalence of and risk factors for healthcare-associated infections in
      Slovenia: results of the second national survey.
AB  - INTRODUCTION: In the second Slovenian national healthcare-associated infections
      (HAIs) prevalence survey, conducted within the European point prevalence survey
      of HAIs and antimicrobial use in acute-care hospitals, we estimated the
      prevalence of all types of HAIs and identified risk factors. METHODS: Patients
      from acute-care hospitals were enrolled into a one-day cross-sectional study in
      October 2011. Descriptive analyses were performed to describe the characteristics
      of patients, their exposure to invasive procedures and the prevalence of
      different types of HAIs. Univariate and multivariate analyses of association of
      having at least one HAI with possible risk factors were performed to identify
      risk factors. RESULTS: Among 5628 patients, 3.8% had at least one HAI and
      additional 2.6% were still being treated for HAIs on the day of the survey; the
      prevalence of HAIs was 6.4%. The prevalence of urinary tract infections was the
      highest (1.4%), followed by pneumoniae (1.3%) and surgical site infections
      (1.2%). In intensive care units (ICUs), the prevalence of patients with at least
      one HAI was 35.7%. Risk factors for HAIs included central vascular catheter
      (adjusted odds ratio (aOR) 4.0; 95% confidence intervals (CI): 2.9-5.7),
      peripheral vascular catheter (aOR 2.0; 95% CI: 1.5-2.6), intubation (aOR 2.3; 95%
      CI: 1.4-3.5) and rapidly fatal underlying condition (aOR 2.1; 95% CI: 1.4-3.3).
      CONCLUSIONS: The prevalence of HAIs in Slovenian acute-care hospitals in 2011 was
      substantial, especially in ICUs. HAIs prevention and control is an important
      public health priority. National surveillance of HAIs in ICUs should be developed
      to support evidence-based prevention and control.

PMID- 27703545
TI  - The role of non-governmental organizations in the mental health area: differences
      in understanding.
AB  - INTRODUCTION: The contribution's aim is highlighting the differences in
      understanding non-governmental organizations' (NGOs) role in the mental health
      area within the public support network for patients with mental health problems
      from various viewpoints, in order to achieve progress in supporting patients with
      mental health problems in local communities. METHODS: Qualitative data gathered
      as a part of a cross-sectional study of NGOs in the support network for patients
      with mental health problems in two Slovenian health regions (56 local
      communities), carried out in 2013 and 2014, were used. Qualitative analysis of
      interviews, focus groups and answers to an open survey question was performed.
      RESULTS: There are differences in understanding NGOs' role in the support network
      for patients with mental health problems, which stem from the roles of
      stakeholders (local community officials, experts, care providers, and patients)
      within this system and their experience. DISCUSSION AND CONCLUSION: The actual
      differences need to be addressed and overcome in order to provide integrated
      community care. The importance of knowing the current state of NGOs in their life
      cycle and the socio-chronological context of the local community support network
      is evident.

PMID- 27703547
TI  - Sensitivity and specificity of the method used for ascertainment of healthcare
      associated infections in the second Slovenian national prevalence survey.
AB  - INTRODUCTION: The second Slovenian national healthcare-associated infections
      (HAIs) prevalence survey (SNHPS) was conducted in acute-care hospitals in 2011.
      The objective was to assess the sensitivity and specificity of the method used
      for the ascertainment of six types of HAIs (bloodstream infections, catheter
      associated infections, lower respiratory tract infections, pneumoniae, surgical
      site infections, and urinary tract infections) in the University Medical Centre
      Ljubljana (UMCL). METHODS: A cross-sectional study was conducted in patients
      surveyed in the SNHPS in the UMCL using a retrospective medical chart review
      (RMCR) and European HAIs surveillance definitions. Sensitivity and specificity of
      the method used in the SNHPS using RMCR as a reference was computed for
      ascertainment of patients with any of the six selected types of HAIs and for
      individual types of HAIs. Agreement between the SNHPS and RMCR results was
      analyzed using Cohen's kappa coefficient. RESULTS: 1474 of 1742 (84.6%) patients
      surveyed in the SNHPS were included in RMCR. The sensitivity of the SNHPS method
      for detecting any of six HAIs was 90% (95% confidence interval (CI): 81%-95%) and
      specificity 99% (95% CI: 98%-99%). The sensitivity by type of HAI ranged from 63%
      (lower respiratory tract infections) to 92% (bloodstream infections). Specificity
      was at least 99% for all types of HAIs. Agreement between the two data collection
      approaches for HAIs overall was very good (kappa=0.83). CONCLUSIONS: The overall
      sensitivity of SNHPS collection method for ascertaining HAIs overall was high and
      the specificity was very high. This suggests that the estimated prevalence of
      HAIs in the SNHPS was credible.

PMID- 27703548
TI  - A methodological approach to the analysis of egocentric social networks in public
      health research: a practical example.
AB  - INTRODUCTION: Research on social networks in public health focuses on how social
      structures and relationships influence health and health-related behaviour. While
      the sociocentric approach is used to study complete social networks, the
      egocentric approach is gaining popularity because of its focus on individuals,
      groups and communities. METHODS: One of the participants of the healthy lifestyle
      health education workshop 'I'm moving', included in the study of social support
      for exercise was randomly selected. The participant was denoted as the ego and
      members of her/his social network as the alteri. Data were collected by personal
      interviews using a self-made questionnaire. Numerical methods and computer
      programmes for the analysis of social networks were used for the demonstration of
      analysis. RESULTS: The size, composition and structure of the egocentric social
      network were obtained by a numerical analysis. The analysis of composition
      included homophily and homogeneity. Moreover, the analysis of the structure
      included the degree of the egocentric network, the strength of the ego-alter ties
      and the average strength of ties. Visualisation of the network was performed by
      three freely available computer programmes, namely: Egonet.QF, E-net and Pajek.
      The computer programmes were described and compared by their usefulness.
      CONCLUSION: Both numerical analysis and visualisation have their benefits. The
      decision what approach to use is depending on the purpose of the social network
      analysis. While the numerical analysis can be used in large-scale population
      based studies, visualisation of personal networks can help health professionals
      at creating, performing and evaluation of preventive programmes, especially if
      focused on behaviour change.

PMID- 27703549
TI  - Neck Circumference in Overweight/Obese Subjects who Visited the Binjai Supermall
      in Indonesia.
AB  - BACKGROUND: Neck circumference (NC) is a simple screening measure for identifying
      overweight and obesity, it reflects upper-body fat distribution and central
      obesity. AIM: To determine whether a single measure of NC might be used to
      identify overweight/obesity. MATERIAL AND METHODS: An observational, analytical,
      cross-sectional study was done. The subjects consisted of all consecutive
      subjects who visited Binjai Supermall (North Sumatera Province, Indonesia)
      between 23rd and 29th September 2015 and agreed to participate in the study. NC,
      weight, height, body mass index (BMI), and waist circumference (WC) were
      measured. Overweight and obesity were defined as BMIs of 23.0-24.9 and >= 25
      kg/m2, respectively. RESULTS: In total, 1554 subjects participated. Of these,
      1238 (79.7%) were overweight/obese. NC correlated significantly with weight,
      height, BMI, and WC. Receiver operating characteristic (ROC) analysis showed that
      for all men and women, the area under the curve of overweight/obesity for NC was
      0.83 and 0.79, respectively. The best NC cutoff points for males and females that
      indicated overweight/obesity were >= 37 cm (sensitivity, 78.3% and specificity,
      75.5%) and >= 33.5 cm (sensitivity, 76.6% and specificity, 66.7%), respectively.
      CONCLUSION: The NC cutoffs that were identified may be useful for screening for
      overweight/obesity and related co-morbidities.

PMID- 27703550
TI  - Serum Interleukin-18 and Its Gene Haplotypes Profile as Predictors in Patients
      with Diabetic Nephropathy.
AB  - BACKGROUND: Diabetic nephropathy (DN) is known as an acute microvascular
      complexity as a subsequence progression in diabetes mellitus type 1 and 2. Many
      evidence pointed that the proinflammatory cytokine Interleukin (IL)-18 might be
      involved in the pathogenesis of DN. AIM: The current study aimed to evaluate the
      association of serum IL-18 and its promoter gene polymorphisms with diabetic
      nephropathy. METHODS: This study included 62 diabetic nephropathy patients (DN
      group) compared to 52 diabetes mellitus patients (DM group). The two groups were
      subjected to anthropometry assessment, molecular studies including SNP genotyping
      by RFLP and finally statistical analysis. RESULTS: The assessment of the serum IL
      18 level and the frequencies of its allele and haplotype: -137G/C, -607C/A and 
      656G/T among the DN and DM subjects revealed that -137G allele has significant
      variation between DN and DM subjects (about 80.8%, P = 0.05) but, no significant
      variation in -607 or -656 alleles IL-18 gene promoter. CONCLUSION: These data
      confirm the impact of high serum IL-18 and the haplotype of the polymorphism
      located in the promoter region of the IL-18 gene with the DN.

PMID- 27703552
TI  - Curative Effect of Aqueous Leaf Extract of Crinum Giganteum on NMDA-Receptor
      Antagonist-Induced Schizophrenic Wistar Rat Model.
AB  - AIM: This study evaluated the curative potential of Crinum giganteum in the
      treatment of schizophrenia using an NMDA-receptor antagonist-induced
      schizophrenic Wistar rat model. METHODS: Twenty-five adult Wistar rats of both
      sexes of average weights 180 g were divided into two groups: control and
      schizophrenic rat models. The controls received 0.1 ml of 0. 9% saline, while
      schizophrenia was induced in models using 25 mg/kg of ketamine hydrochloride
      (i.p.) for 7 days. On the 8 day models were divided into group's k1, k2, k3 and
      k4 of 5 rats each. K1 and the controls were sacrificed then, groups k2 and k3
      were treated with 5 mg/kg and 10 mg/kg aqueous leaf extract of Crinum giganteum
      while, k4 (standard) received 25 mg/kg of chlorpromazine orally for 28 days.
      Amygdala were harvested, processed and stained with Haematoxylin and Eosin (H &E)
      stain, Neuron-specific enolase (NSE) marker was also used to monitor the curative
      effect on the amygdala. RESULTS: Degenerative changes and increased NSE
      immunoreactivity were observed in the untreated models. Extract-treated models
      showed normal amygdala and negative NSE immunoreactivity while chlorpromazine
      treated models revealed decreased NSE immunoreactivity. CONCLUSION: Crinum
      giganteum extracts exhibits better curative effect than the standard
      antipsychotic agent.

PMID- 27703553
TI  - Influence of Parental and Some Demographic Characteristics on Overweight/Obesity
      Status among a Sample of Egyptian Children.
AB  - BACKGROUND: Overweight/obesity is a multi-factorial problem, which results from
      rapidly changing social, economic, and physical environments that have led to an
      energy imbalance. AIM: To identify the association between childhood
      overweight/obesity and some socio-demographic risk factors, as parental age, body
      mass index (BMI), education and occupation, family size and residence
      (urban/rural). SUBJECTS AND METHODS: Cross-sectional study included 154 children
      of both sexes; aged 5-18 years; with their parents; one of them was working at
      the National Research Centre and from their relatives and neighbours. Data was
      collected about the child birth weight, family size, parental ages, education,
      occupation and place of residence. Anthropometric measurements including weight,
      height, and body mass index (BMI) of children and their parents were conducted.
      RESULTS: Obesity was detected among 19.5% of children (BMI > 95th percentile),
      75.3% of their mothers and 49.6% of their fathers (BMI > 30 Kg/m^2). While
      overweight was present in 11.0% of the children (BMI > 85th- <95 percentile),
      16.9% of their mothers and 36.5% of their fathers (BMI > 25-29.9 Kg/m^2). Child
      obesity was more prominent in urban than rural areas (21.3% versus 12.5%) and
      among housewives (22.8%) than among working mothers (16%, p < 0.016). Child
      overweight was more common in rural than urban areas (12.5% versus 10.7%) and
      among children with high father education (20%). Child BMI had significant
      positive correlations only with the child age, parental ages and BMIs, and family
      size. In spite of that, parental BMIs had significant positive correlations with
      each other and with family size, and significant negative correlations with
      maternal education and occupation and paternal education. CONCLUSION: Childhood
      obesity and overweight were more prominent in urban than rural areas, among
      children with non-working housewives mothers and highly educated fathers (college
      or above). Parental education and occupation had an indirect significant effect
      on child BMI through their significant effect on parental BMIs.

PMID- 27703551
TI  - Protective Effects of Vasodilatory Betaeta-Blockers Carvedilol and Nebivolol
      against Glycerol Model of Rhabdomyolysis-Induced Acute Renal Failure in Rats.
AB  - BACKGROUND: Rhabdomyolysis (RM)-induced acute renal failure (ARF) accounts for
      about 10-40% of all cases of ARF. AIM: The present study investigated the
      possible protective effect of two nitric oxides (NO)-releasing third generation
      beta-blockers, carvedilol (Carv) and nebivolol (Nebi), against RM-mimicking
      glycerol (Gly)-induced ARF in rats. MATERIAL AND METHODS: After 24 h dehydration,
      rats received a single dose of 50% Gly (8 ml/kg, im). They were treated with
      vehicle, Carv (2.5 mg/kg/day, po) or Nebi (10 mg/kg, po) for 3 successive days
      starting from an hour prior to Gly injection. Evaluation of blood pressure and
      locomotor activity was performed during the experiment. 72 h following Gly
      administration, total protein in the urine, serum levels of creatinine, blood
      urea nitrogen, sodium and potassium as well as the renal contents of
      malondialdehyde, reduced glutathione and NO were assessed, together with a
      histopathological examination of renal tissues. RESULTS: Carv and Nebi attenuated
      Gly-induced renal dysfunction and histopathological alterations. They decreased
      the Gly-induced oxidative stress and increased renal NO concentration.
      Restoration of normal blood pressure and improvement of locomotor activity were
      also observed. CONCLUSION: The results clearly demonstrate protective effects of
      Carv and Nebi against renal damage involved in RM-induced ARF and suggest a role
      of their antioxidant and NO-releasing properties.

PMID- 27703554
TI  - New Era for Usage of Serum Liver Enzymes as A Promising Horizon for the
      Prediction of Non-Alcoholic Fatty Liver Disease.
AB  - BACKGROUND: Liver histology remains the gold standard for assessing non-alcoholic
      fatty liver disease (NAFLD). Noninvasive serological markers and radiological
      methods have been developed to evaluate steatosis to avoid biopsy. AIM: To put
      cutoff value for liver enzymes that could predict non-alcoholic steatohepatitis
      (NASH). PATIENTS AND METHODS: This study was conducted on 54 patients (with NAFLD
      diagnosed by the US). Patients were subjected to history, physical,
      anthropometric measurements, investigations including liver enzymes, abdominal
      US, and liver biopsy. According to biopsy results, patients were subdivided
      according to NASH development. Also, biopsy results were correlated to the levels
      of liver enzymes. RESULTS: Forty-seven patients who were suspected to have NAFLD
      by sonar were confirmed by biopsy. There was a significant correlation between
      steatosis degree in biopsy and sonar. Correlation study between steatosis in
      biopsy and ALT level showed highly significant positive correlation. Correlation
      study between steatosis in biopsy on one side & AST and GGT on the other side
      showed significant positive correlation. Cutoff value for detection of NASH using
      ALT & AST & and GGT were 50.5, 56, 60.5 respectively with sensitivity = 95.5,
      90.5, 86.4 % and specificity = 93.8, 100, 87.5%. CONCLUSION: Cut off values of
      liver enzymes can be combined with abdominal sonar to predict NASH.

PMID- 27703555
TI  - Dietary Behaviour Pattern and Physical Activity in Overweight and Obese Egyptian
      Mothers: Relationships with Their Children's Body Mass Index.
AB  - BACKGROUND: Obesity and related morbidity increase in Egyptian women and their
      children. A better understanding of dietary and activity patterns is needed to
      reduce obesity prevalence. AIM: The present study aimed to assess dietary
      patterns and physical activity in Egyptian overweight and obese mothers and to
      explore its relationships with their children's body mass index (BMI). SUBJECTS
      AND METHODS: This descriptive case-control study was conducted at the National
      Research Center. The study included a sample of 64 overweight and obese mothers
      and 75 children, compared with apparently healthy non-obese mothers and their
      children of matched age and social class. Tested questionnaires were used to
      collect information of the studied subjects. RESULTS: A statistically
      significantly higher incidence of unemployment, large family size was observed in
      overweight & obese women compared to controls (P < 0.05). Those women who
      consumed vegetables more than 3 times a week were less likely to be overweight or
      obese (P < 0.05). No significant association were detected between mothers'
      physical activity, dietary behaviour variables and children's BMI except for
      consuming beverages with added sugar (95%CI = 0.074-0.985, P<0.05). CONCLUSION:
      Improper dietary patterns, nonworking mothers and big family size are associated
      with obesity among Egyptian women. Emphasis should be given to increasing
      physical activity and encourage healthier diets among Egyptian mothers and their
      children.

PMID- 27703556
TI  - Serum IL-10, MMP-7, MMP-9 Levels in Helicobacter pylori Infection and Correlation
      with Degree of Gastritis.
AB  - AIM: Helicobacter pylori causes gastric mucosal inflammation and immune reaction.
      However, the increase of IL-10, MMP-7, and MMP-7 levels in the serum is still
      controversial. The objective of this study was to investigate the serum levels of
      IL-10, MMP-7 & MMP-9 in gastritis patients with H. pylori infection. MATERIALS
      AND METHODS: A cross-sectional study was done on seventy gastritis patients that
      consecutive admitted to endoscopy units. The diagnosis of gastritis was made
      based on histopathology and diagnosis of H. pylori infection was based on rapid
      urease test. Serum samples were obtained to determine to circulate IL-10, MMP-7,
      and MMP-9 level. Univariate and bivariate analysis were done by SPSS version 22.
      RESULTS: Forthy percentages of the patients were infected with H. pylori. The IL
      10 level was significantly higher in H. pylori-infected patients compared to non
      infected patients. However, there were no differences between serum levels of MMP
      7 and MMP-9 in infected and non-infected H. pylori patients. CONCLUSIONS: The
      immune response to H. pylori promotes systemic inflammation, which was reflected
      by the increased levels of serum IL-10. However, there were no significant
      differences in MMP-7 and MMP-9 serum levels between positive and negative
      infected H. pylori patients.

PMID- 27703557
TI  - Immunomodulatory Effect of H. Pylori CagA Genotype and Gastric Hormones On
      Gastric Versus Inflammatory Cells Fas Gene Expression in Iraqi Patients with
      Gastroduodenal Disorders.
AB  - AIM: To evaluate the Immunomodulatory effects of CagA expression; pepsinogen I,
      II & gastrin-17 on PMNs and lymphocytes Fas expression in inflammatory and
      gastric cells; demographic distribution of Fas molecule in gastric tissue and
      inflammatory cells. METHODS: Gastroduodenal biopsies were taken from 80 patients
      for histopathology and H. pylori diagnosis. Serum samples were used for
      evaluation of pepsinogen I (PGI); (PGII); gastrin-17 (G-17). RESULTS: Significant
      difference (p < 0.001) in lymphocytes & PMNs Fas expression; epithelial & lamina
      propria Fas localization among H. pylori associated gastric disorders. No
      correlation between grade of lymphocytes & PMNs Fas expression in gastric
      epithelia; lamina propria and types of gastric disorder. Significant difference
      (p < 0.001) in total gastric Fas expression, epithelial Fas; lamina propria and
      gastric gland Fas expression according to CagA, PGI; PGII; PGI/PGII; Gastrin-17.
      Total gastric Fas expression has significant correlation with CagA, PGII levels.
      Gastric epithelial and gastric lamina propria Fas expression have significant
      correlation with CagA, PGI; PGII levels. Significant difference (p < 0.001) was
      found in lymphocytes & PMNs Fas expression; epithelial & lamina propria
      localization of lymphocytes & PMNs Fas expression according to CagA, PGI; PGII;
      PGI/PGII; Gastrin-17. Lymphocytes Fas expression have correlation with PGI, PGII,
      PGI/PGII. PMNs Fas expression have correlation with PGI, PGII. CONCLUSION: Fas
      gene expression and localization on gastric and inflammatory cells affected
      directly by H. pylori CagA and indirectly by gastric hormones. This contributes
      to progression of various gastric disorders according to severity of CagA induced
      gastric pathology and gastric hormones disturbance throughout the course of
      infection and disease.

PMID- 27703558
TI  - Diagnostic Accuracy of Acoustic Radiation Force Impulse (ARFI) in Diagnosis of
      Liver Fibrosis among Egyptian Patients with Chronic HCV Infection.
AB  - BACKGROUND: Acoustic radiation force impulse (ARFI) evaluates liver stiffness non
      invasively and was invented recently. This technique can easily and accurately
      assess the degree of liver fibrosis in clinical practice. AIM: The aim of this
      study was to detect the diagnostic performance of ARFI elastography in the
      staging of fibrosis in some Egyptian patients with chronic HCV infection.
      PATIENTS AND METHODS: One hundred ninety patients with chronic HCV infection; 142
      men and 48 women were enrolled in the study. They underwent liver biopsy
      examination for liver fibrosis detection. All demographic; clinical and
      biochemical data were recoded. ARFI examination was done for all subjects to
      detect liver stiffness measurement in relation to liver fibrosis detected by
      pathological examination of liver biopsies. RESULTS: Medians of liver stiffness
      measurement by shear wave velocity showed a significant increase as a grade of
      liver fibrosis increases (p <= 0.0001, highly significant). Liver stiffness was
      directly correlated to age, AST; ALT; INR and liver steatosis (p values were:
      0.009; 0.0001; 0.013; 0.006 and 0.04 respectively, significant). On the other
      hand, liver stiffness was inversely correlated to albumin; prothrombin
      concentration and platelets (p values were: 0.0001; 0.001, and 0.0001,
      respectively, significant). We found that shear wave velocity can predict F1; F2;
      F3 and F4 at cut-off values: 1.22; 1.32; 1.44 and 1.8 respectively. CONCLUSION:
      ARFI is a diagnostic noninvasive promising technique for liver fibrosis diagnosis
      among Egyptian patients with chronic HCV infection.

PMID- 27703559
TI  - Risk Factors of End Stage Renal Disease in Peshawar, Pakistan: Odds Ratio
      Analysis.
AB  - AIM: The basic aim of this study was to discover the association of End Stage
      Renal Disease (ESRD) with various risk factors. End Stage Renal Failure is the
      last stage of the chronic renal failure in which kidneys become completely fail
      to function. MATERIALS AND METHODS: The data were collected from the patients of
      renal diseases from three major hospitals in Peshawar, Pakistan. Odds ratio
      analysis was performed to examine the relationship of ESRD (a binary response
      variable) with various risk factors: Gender, Diabetic, Hypertension,
      Glomerulonephritis, Obstructive Nephropathy, Polycystic kidney disease, Myeloma,
      SLE Nephritis, Heredity, Hepatitis, Excess use of Drugs, heart problem and
      Anemia. RESULTS: Using odds ratio analysis, the authors found that the ESRD in
      diabetic patients was 11.04 times more than non-diabetic patients and the ESRD
      were 7.29 times less in non-hypertensive patients as compared to hypertensive
      patients. Similarly, glomerulonephritis patients had 3.115 times more risk of
      having ESRD than non-glomerulonephritis. Other risk factors may also, to some
      extent, were causes of ESRD but turned out insignificant due to stochastic
      sample. CONCLUSION: The authors concluded that there is a strong association
      between ESRD and three risk factors, namely diabetes, hypertension and
      glomerulonephritis.

PMID- 27703560
TI  - Patients with Schizophrenia and Social Contacts.
AB  - BACKGROUND: Patients with schizophrenia have severe problems with personal and
      social relations which affect their quality of life. AIM: The aim of the paper
      was to monitor personal and social relations in patients with schizophrenia and
      to find out the differences regarding socio-demographic characteristics and
      ambulatory and day hospital treatment. MATERIAL AND METHODS: The investigation
      included 120 subjects each with diagnosis F20 according to ICD 10 criteria;
      divided into two groups of 60 patients regarding their actual treatment (the
      first group received ambulatory care whereas those from the second group had a
      day hospital treatment). Patients were of different age and gender, receiving
      regular antipsychotic therapy. They were included in individual and group
      psychosocial therapeutic procedures during the day hospital treatment. The
      investigation utilised the following diagnostic instruments: standardised
      clinical interview and Personal and social performance scale (PSP scale), a non
      standardized questionnaire of socio-demographic data, family support and
      existence of mental disorder in other family members. RESULTS: The results have
      shown better personal and social functioning in patients who had family support,
      in those who are employed, in those with no mental disorder in other family
      members and in patients on day hospital treatment against patients receiving
      ambulatory care. CONCLUSION: Day hospital treatment, family support and social
      support improve the ability for personal and social contacts of patients with
      schizophrenia.

PMID- 27703561
TI  - Ketamine Sedation in Gastrointestinal Endoscopy in Children.
AB  - BACKGROUND: Moderate sedation for gastrointestinal endoscopy has traditionally
      been provided by the endoscopist. Controversy has ensued over safe and efficient
      sedation practice as endoscopy has increased in numbers and complexity. AIM: To
      evaluate the safety of ketamine sedation given by non-anesthesiologist during
      gastrointestinal endoscopy in children. METHODS: A prospective study of 100
      paediatric patients with gastrointestinal symptoms who were a candidate for upper
      or lower gastrointestinal endoscopy in paediatric endoscopy unit at Abo El-Reesh
      Paediatric Hospital, Cairo University. All children were > 2 years old and
      weighed > 6 kg. The analysis was performed in terms of sedation-related
      complications. RESULTS: A total 100 paediatric patients including 53 males and 47
      females with mean age of 5.04 years were involved in the study. All children were
      medicated with ketamine with a mean dose of 3.77mg/kg. No complications occurred
      in 87% of cases. Desaturation occurred in 13% of the cases and was reversible by
      supplemental nasal oxygen. Desaturation was more frequent during Upper GI
      Endoscopy and with the intramuscular route (p value=0.049). No apnea,
      bradycardia, arrest or emergence reactions were recorded. CONCLUSION: Ketamine
      sedation found to be safe for paediatric gastrointestinal endoscopy in Egyptian
      children without co-morbidities. Transient Hypoxia (13%) may occur but easily
      reversed by nasal oxygen therapy.

PMID- 27703562
TI  - Justification for Rhinoseptoplasty in Children - Our 10 Years Overview.
AB  - BACKGROUND: Nasal septal surgery and rhinoplasty are controversial in children.
      Traditionally, an attitude of restraint has been employed by most surgeons till
      an empirical age of 16 to 18 years. This is to avoid the possible adverse effects
      that the growth spurts may have on the nose and midface region. AIM: The aim of
      this paper was to present the results of rhinoplasty in children in order to
      restore the anatomy and function or to promote normal development and outgrowth
      of the nose. MATERIAL AND METHODS: Ninety seven children aged 6-14, with severe
      nose deformities and breathing problems through the nose, were admitted for
      septo/rhinoplasty at the University Clinic for Ear, Nose and Throat, Faculty of
      Medicine, Ss Cyril and Methodius University of Skopje, Republic of Macedonia. At
      our Clinic, they have been observed and photographed (with parent permission) in
      the period of 10 years (2006-2016). The most frequent cause of these deformities
      was the nasal trauma in early childhood which was ignored or untreated. All of
      them rhino/septoplasty were indicated in accordance with the above-mentioned
      recommendations for rhino/septoplasty in early childhood and in adolescents.
      RESULTS: In 51 children and adolescents septoplasty were prepared. Mostly there
      was a group of younger children age from 6-10 (68%) and adolescents (32%). In the
      other 31 children and adolescents, septorhinoplasty was prepared. Mostly there
      were children older than 12 years old and adolescents (70%). Only 30% were
      younger than 12 years, of course with severe nasal breathing problems, nasal
      septal deformities and deformities of the nasal pyramid. CONCLUSION: The growth
      centres of the nose have to be avoided if possible; long-term nasal issues will
      theoretically be minimised. If the surgeon replaces it, the cartilage of the nose
      becomes straighter but still intact.

PMID- 27703563
TI  - Automated Versus Manual Blood Pressure Measurement: A Randomized Crossover Trial
      in the Emergency Department of a Tertiary Care Hospital in Karachi, Pakistan: Are
      Third World Countries Ready for the Change?
AB  - BACKGROUND: Hypertension has proven to be a strong liability with 13.5% of all
      mortality worldwide being attributed to elevated blood pressures in 2001. An
      accurate blood pressure measurement lies at the crux of an appropriate diagnosis.
      Despite the mercury sphygmomanometer being the gold standard, the ongoing
      deliberation as to whether mercury sphygmomanometers should be replaced with the
      automated oscillometric devices stems from the risk mercury poses to the
      environment. AIM: This study was performed to check the validity of automated
      oscillometric blood pressure measurements as compared to the manual blood
      pressure measurements in Karachi, Pakistan. MATERIAL AND METHODS: Blood pressure
      was recorded in 200 individuals aged 15 and above using both, an automated
      oscillometric blood pressure device (Dinamap Procare 100) and a manual mercury
      sphygmomanometer concomitantly. Two nurses were assigned to each patient and the
      device, arm for taking the reading and nurses were randomly determined. SPSS
      version 20 was used for analysis. Mean and standard deviation of the systolic and
      diastolic measurements from each modality were compared to each other and P
      values of 0.05 or less were considered to be significant. Validation criteria of
      British Hypertension Society (BHS) and the US Association for the Advancement of
      Medical Instrumentation (AAMI) were used. RESULTS: Two hundred patients were
      included. The mean of the difference of systolic was 8.54 +/- 9.38 while the mean
      of the difference of diastolic was 4.21 +/- 7.88. Patients were further divided
      into three groups of different systolic blood pressure <= 120, > 120 to = 150 and
      > 150, their means were 6.27 +/- 8.39 (p-value 0.175), 8.91 +/- 8.96 (p-value
      0.004) and 10.98 +/- 10.49 (p-value 0.001) respectively. In our study 89 patients
      were previously diagnosed with hypertension; their difference of mean systolic
      was 9.43 +/- 9.89 (p-value 0.000) and difference of mean diastolic was 4.26 +/-
      7.35 (p-value 0.000). CONCLUSIONS: Systolic readings from a previously validated
      device are not reliable when used in the ER and they show a higher degree of
      incongruency and inaccuracy when they are used outside validation settings. Also,
      readings from the right arm tend to be more precise.

PMID- 27703564
TI  - Role and Importance of Chlamydia Trachomatis in Pregnant Patients.
AB  - AIM: The aim of this study was to assess the prevalence of chlamydial infection
      among pregnant women and to determine the role of this infection in the fetus.
      MATERIAL AND METHODS: In the first phase of this study were reported 58 pregnant
      women with a positive test for active chlamydial infection by applying
      immunofluorescence. In the second phase of the study were reported pregnant with
      premature burst membranes (PBM), postnatal complications associated with
      chlamydial infection as puerperal endometritis, and newborns are monitored for
      low birth weight and growth retardation at birth. RESULTS: With a positive test
      are 58 patients in the first trimester or pregnancy registration in our
      consultation. After regimen with Sumamed (2 x 500 mg for three days and after 10
      days again same scheme for them and their partner) at the beginning of the third
      trimester, the PCR test was made again. Of these, 5 were positive again,
      participants are between 20 and 30 years old. With premature rupture of OM are 20
      patients. There was no increased incidence of premature births. Infants born to
      infected mothers have a higher risk of developing respiratory symptoms in the
      first 60 days of life. 3 of them have low for his age bodyweight. CONCLUSIONS:
      The scarcity of data on manifestations of chlamydial infection during pregnancy
      and neonatal outcomes justifies this study. Early diagnosis for registration of
      pregnancy and timely treatment of chlamydial infection as well as scrutinising
      the infection during the third trimester of pregnancy can prevent infection of
      the newborn. Therefore, preventive examinations should be considered as a
      priority for early detection of asymptomatic chlamydial infection in the conduct
      of antenatal care.

PMID- 27703565
TI  - The Impact of the Nasal Trauma in Childhood on the Development of the Nose in
      Future.
AB  - AIM: To prevent and to treat nasal trauma in children properly, because it can
      lead to displacement or depression of the nasal bones or septum. Second, our aim
      was, for the patient to recognise and create a mature decision for eventual nose
      changes which will be made with the operative intervention or they are not mature
      enough and the decisions were made by their parents. MATERIAL AND METHODS: Our
      retrospective study was made at University Clinic for Ear, Nose and Throat,
      Faculty of Medicine, Ss Cyril and Methodius University of Skopje in the period of
      6 years (2005-2016). Seventy-three patients were admitted with recent or previous
      nasal trauma or nasal deformity. The first group of 32 were children and
      adolescents from 6-14 years old who were admitted to our hospital because of
      recent nasal trauma. The second group of 41 children and adolescents from 6-14
      years old were admitted to our hospital because of previous nasal trauma, which
      was not treated on time, or it was not treated properly. They were admitted to
      our clinic for surgical intervention septo/rhinoplasty. The second group of
      patients fills the brief psychological questioner prepared by Clinical
      psychiatrist from University Clinic of Psychiatry, in Skopje, and their
      psychological reactions were taken into consideration. RESULTS: Eleven of the
      children and adolescents who had nasal fracture without dislocation, who have no
      symptoms, minimal swelling, and no septal deviation or hematoma, were observed
      with a specific follow-up: 3 days after nasal fracture, then every week in the
      first month, after 1 month, and after 3 months period. Sixteen of children and
      adolescents who had a nasal fracture with subluxation of nasal septum were
      operated with closed reduction (repositio nasi) under general anaesthesia. The
      others with septal hematomas and subperichondrial abscess were treated as in
      adults' patients. The second group of 41 children and adolescents from 6-14 years
      old consisted with with the previous nasal trauma which was not treated on time
      or it was improperly treated. In 24 (58.54%) of these patients septoplasty was
      performed and in 17 (41.46%) was performed rhino septoplasty. CONCLUSION: Often,
      difficult septal deformations in children are followed with deformation of the
      nasal pyramid (rhino scoliosis, rhino lordosis). In those cases, we cannot solve
      septal pathology without nasal pyramid intervention in the same time and
      opposite. Clinical reports have not produced solid evidence for the statement
      that septal surgery has no negative effect on nasal growth or can serve for
      correcting abnormal growth. The functional and esthetic problems of the patient,
      however, mean a continuous stimulus for further clinical and experimental
      investigations.

PMID- 27703566
TI  - Early Prognostic Factors for the Progress of Preeclampsia - Our Experience in the
      Period 2010-2011.
AB  - AIM: To determine the prognostic value of the low Pregnancy-associated plasma
      protein A (PAPP-A) levels in the early stages of pregnancy (11-13 weeks GA)
      independently and in combination with a Doppler test of the uterine arteries
      during the second half of pregnancy (22-23 weeks GA). MATERIAL AND METHODS: The
      study covered the period 2010-2011 and included 106 pregnant women, aged 35-40,
      with a single child pregnancy. The research excluded pregnant women with
      anomalies of the fetus, smokers and women taking prophylactically low doses of
      aspirin. RESULTS: Thirty-six pregnant women had PAPP-A level below 0.4 MoM,
      whereas 20 of them developed preeclampsia and 7 - early preeclampsia. The
      combination of the low PAPP-A values and the abnormal Doppler test of the uterine
      arteries is with a considerably better prognostic value in regards to the risk of
      developing preeclampsia. CONCLUSION: The Doppler test is a non-invasive, quick
      and easy method for assessment of the uterine-placental blood flow.

PMID- 27703567
TI  - The Association between Malnutrition and Pressure Ulcers in Elderly in Long-Term
      Care Facility.
AB  - BACKGROUND: Malnutrition is common in elderly and is a risk factor for pressure
      ulcers. AIM: The aim of the present study was to determine the prevalence of
      malnutrition in geriatric and palliative patients hospitalised in long-term care
      facility, and to examine the influence of nutritional status on the prevalence of
      pressure ulcers (PU). MATERIAL AND METHODS: Descriptive, observational and cross
      sectional study including 2099 patients admitted to the Hospital during a 24
      month period (January 2013 to December 2014). We recorded: demographic data, body
      mass index (BMI), Braden score, laboratory parameters of interest (albumin, total
      protein, RBC count, haemoglobin and iron levels) and presence or absence of
      malnutrition and pressure ulcers. RESULTS: The pressure ulcer prevalence was
      12.9% (256 out of 2099). Based on the BMI classification, 61.7% of patients had a
      good nutritional status, 27.4% were undernourished, and 2.1% were considered
      malnourished. Nutritional status was statistically significantly different
      between patients with and without PU (p < 0.0001). This study also showed that
      hypoproteinemia, hypoalbuminemia, low RBC was positively associated with PU
      prevalence. CONCLUSION: The results highlight the impact of nutritional status on
      the prevalence of pressure ulcers in hospitalised geriatric and palliative
      population. It is of paramount importance to correctly evaluate the presence of
      malnutrition in patients at risk of pressure ulcers.

PMID- 27703568
TI  - Clinical, Laboratory and Radiographic Features of Patients with Pneumonia and
      Parapneumonic Effusions.
AB  - BACKGROUND: Parapneumonic effusions complicating pneumonia are associated with
      increased morbidity and mortality. AIM: To determine the role of the clinical,
      laboratory and radiographic features to the differential diagnosis of patients
      with community- acquired pneumonia (CAP) without effusion, uncomplicated
      parapneumonic effusion (UCPPE) and complicated parapneumonic effusion (CPPE).
      MATERIAL AND METHODS: We analysed 148 patients with CAP without effusion, 50 with
      UCPPE and 44 with CPPE. In three groups of patients, the majority was male
      patients (58.11%, 58%, 61.36%) consequently. RESULTS: The chronic heart failure
      was the most common comorbidity in a group with CAP (28; 18.92%) and UCPPE (7;
      14%), alcoholism (12;12.77%) in a group with CPPE. Patients with CPPE had
      significantly longer fever compared to patients with CAP without effusion (p =
      0.003). Pleuritic chest pain (86.36%) and dyspnea (88.64%) were the most common
      symptoms in CPPE, then to group with UCPPE (60%; 52%), and in CAP without
      effusion (25.68%; 47,97%). Diffuse pulmonary changes were detected more
      frequently in the group with CAP without effusion compared with the group with
      CPPE (64.86 % vs. 27.27 %), while the segment lung changes were more common in
      patients with CPPE (50% vs. 20.27%). Patients with CPPE were significant with
      higher erythrocytes sedimentation rate (ESR), white blood cells (WBC) and serum C
      reactive protein (CRP) than it the other two groups (p = 0.00090, p = 0.01, p=
      0.000065). CONCLUSION: Proper analysis of clinical, laboratory and radiographic
      features of patients with CAP and parapneumonic effusion can prevent
      mismanagement in these patients and will reduce morbidity and mortality.

PMID- 27703569
TI  - Heart Failure Predictors in a Group of Patients with Myocardial Infarction.
AB  - AIM: The present study considers of the prevalence of heart failure (HF) in
      patients suffering from acute myocardial infarction (AMI) in the University
      Hospital Centre of Tirana (UHCT) "Mother Theresa"; the demographic and clinical
      characteristics of the sample during hospitalization; and the main predictors of
      heart failure occurrence inside the group of patients suffering an AMI. MATERIAL
      AND METHODS: During a period of study from 2013-2015 we studied demographic and
      clinical data from 587 consecutive patients presenting with AMI; Framingham
      criteria were adopted for classifying patients with HF upon admission. RESULTS: A
      Killip class >= 2 was the main diagnostic criterion of HF during hospitalisation.
      HF was identified in 156 patients (26.6%). The subgroup with HF had significant
      differences when compared with the other patients with regard to age, sex (male),
      heart rate upon admission, systolic blood pressure on admission, previous
      episodes of AMI, glycemia on admission, previous antihypertensive treatment,
      previous revascularization procedures, peripheral vascular disease, chronic renal
      disease, ejection fraction (EF), anemia, and atrial fibrillation presence.
      Independent predictors for HF occurrence in the logistic regression model were
      EF, previous revascularization, peripheral vascular disease, age, sex, previous
      AMI, systolic blood pressure upon admission, and anaemia. CONCLUSION: As a
      conclusion, HF seems to be a common occurrence after AMI, in spite of changes in
      the epidemiological profile of the acute coronary syndrome. An increase in the
      incidence is registered as well, parallel to a decrease in the mortality
      following AMI. Attention must be shown for highly risked subpopulations, aged
      persons, patients with the previous coronary disease, and concomitant conditions.

PMID- 27703570
TI  - Two Pregnancies with a Different Outcome in a Patient with Alport Syndrome.
AB  - BACKGROUND: Alport syndrome is a genetic disease that progresses to chronic
      kidney failure, with X-linked, autosomal dominant or autosomal recessive type of
      inheritance. Women are generally carriers of the mutation and have a milder form
      of the disease. During pregnancy, they have an increased risk of impaired kidney
      function and preeclampsia. CASE PRESENTATION: A 27-year old woman, gravida 1,
      para 0, in her 23rd gestational week came to the outpatient unit of the
      University Clinic of Nephrology for the first time because of slowly progressing
      proteinuria and Alport syndrome. She was admitted to the gynaecological ward in
      her 29th gw for proteinuria which increased from 3.8 g/day up to 20 g/day and the
      serum creatinine increased to 120- 150 micromol/l. She was delivered in the 30th
      gestational week due to obstetrical indications with a cesarian section and
      delivered a baby with a birth weight of 880 g. After delivery, proteinuria
      decreased to 2 g/d within 2 months and an angiotensin-converting enzyme inhibitor
      (ACEI) was started. Her second pregnancy, after 2 years, had an uneventful course
      and she delivered a healthy baby weighing 3000 g in the 39th week. Six months
      after the second delivery, her renal function remained normal and her proteinuria
      was 2 g/d. CONCLUSIONS: Pre-pregnancy counselling and frequent controls during
      pregnancy are necessary for women with Alport syndrome, as well as regular
      monitoring after delivery. Recent reports are more in favour of good pregnancy
      and nephrological outcomes in women with Alport syndrome when renal disease is
      not advanced.

PMID- 27703571
TI  - The Role of Rehabilitation in the Management of Patients with Charcot-Marie-Tooth
      Disease: Report of Two Cases.
AB  - BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a hereditary disease with signs
      of chronic non-progressive motor-sensory neuropathy which is characterised by
      symmetric muscle atrophy and weakness of the distal portion of lower extremities.
      AIM: The aim is to present two cases with peroneal muscular atrophy, applied
      rehabilitation procedures and rehabilitation outcome. MATERIAL AND METHODS:
      Patient DR, aged 51, and patient KH, aged 78. Both patients had weakness and
      pronounced atrophy of the distal portion of lower extremities, numbness down the
      legs, contractures in the ankles and walking difficulties. Evaluation of patients
      included a clinical examination, Barthel Index, Time Up and Go test, measurement
      of the ankle range of motion, and a manual muscle test. On admission, the Barthel
      Index score was 60 in the first case, and 80 in the second. The rehabilitation
      program included exercise therapy with for lower extremity, occupational therapy,
      stationary bicycle riding, galvanic current, water exercises, and ankle-foot
      orthoses for both legs. RESULTS: The therapy applied had no significant changes
      in the clinical neurological status of the patients, but yet it provided some
      improvement in ankle contractures, better mobility, and a more stable gait.
      CONCLUSION: The application of rehabilitation procedures in patients with Charcot
      Marie-Tooth disease can improve their functional status and walking stability.

PMID- 27703572
TI  - Cytomegalovirus Infection during Pregnancy and Its Impact on the Intrauterine
      Fetal Development - Case Report.
AB  - AIM: The aim of this publication is to present a case of CMV infection during
      pregnancy, with clinical manifestations of the development of microcephaly and
      simultaneous dilatation of the 3rd and 4th brain ventricle at 23 weeks gestation.
      This article discusses the role of ultrasound screening in the second trimester
      of pregnancy. CASE PRESENTATION: We present the case of a 25-year-old woman with
      the initials S.K. in her second pregnancy that came to our antenatal Consulting
      Centre. The first screening for blood count, blood group, biochemistry and
      serology showed results within the reference range. The patient came for a second
      comprehensive biochemical screening at 17 - 18 weeks gestation. The results
      showed the low genetic risk of congenital anomalies. Fetal morphology of the
      fetus was normal. S.K. came again for consultation at 22 weeks gestation in
      connection with the admittance of her first 3-year-old child to the hospital
      because of pneumonia. Serological tests of the child had shown elevated CMV titer
      - specific IgM. Then we made new serological tests of the patient and the results
      have shown that the patient was most likely infected by CMV primarily in the
      first trimester of pregnancy. After consulting about the risk of transmission of
      CMV to the fetus, the woman chose monthly ultrasound scans and refused
      amniocentesis. At 36 weeks gestation, in addition to the microcephaly already
      established, enlargement of the IV brain ventricle at the expense of
      underdevelopment of the cerebellum was noticed. Also, 2nd to 3rd stage of
      placenta maturity and low quantity of amniotic fluid was established. A male
      fetus of weight 2,890 g and height 50 cm was delivered. The fetus was with skin
      petechiae and hepatosplenomegaly. Neurological examination showed no
      abnormalities. CONCLUSIONS: In the described case the time interval between
      infection and ultrasonic manifestations is more than 17 weeks. The long interval
      between infection and occurrence of ultrasound markers can be a good prediction
      sign, as it may reflect less aggressive viral infection than present in cases
      where similar ultrasound findings were obtained shortly after infection of the
      mother.

PMID- 27703573
TI  - Enduring Personality Changes after Intense Stressful Event: Case Report.
AB  - BACKGROUND: World statistical data show that a large number of individuals suffer
      from posttraumatic stress disorder (PTSD) after exposure to the intense traumatic
      event. PTSD can have a chronic course with enduring changes in the functioning of
      the person. CASE PRESENTATION: Here we report two adult individuals of different
      gender and education who were exposed to the extremely severe stressful event
      after which difficulties in psychological functioning developed. The first case
      we present is a 46-year-old man, with completed high education, divorced, father
      of two children, who lives with his parents, and is retired. Disorders appeared
      20 years ago when he was exposed to extremely severe stressful events in war
      circumstances that included captivity, torture, and loss of fellow soldiers. The
      second case is a 50-year-old female patient, with a university degree, professor
      of art, married, and mother of two children of whom the son died six years ago.
      She suffered from disorders after the sudden injury of her son that ended with
      his death. CONCLUSION: Posttraumatic stress disorder after the intense stress is
      a risk of development enduring personality changes with serious individual and
      social consequences.

PMID- 27703574
TI  - Aortic Annular Enlargement during Aortic Valve Replacement.
AB  - In the surgery of aortic valve replacement is always attempted, as much as
      possible, to implant the larger prosthesis with the mains goals to enhance the
      potential benefits, to minimise transvalvular gradient, decrease left ventricular
      size and avoid the phenomenon of patient-prosthesis mismatch. Implantation of an
      ideal prosthesis often it is not possible, due to a small aortic annulus. A
      variety of aortic annulus enlargement techniques is reported to avoid patient
      prosthesis mismatch. We present the case that has submitted four three times open
      heart surgery. We used Manouguian technique to enlarge aortic anulus with
      excellent results during the fourth time of surgery.

PMID- 27703575
TI  - Mental Health Legislation and Involuntary Hospitalization in the Republic of
      Macedonia.
AB  - As psychiatrists, we are often obliged to provide non-consensual treatment. This
      institute comprises the rights of the patients with mental health disorders. The
      aim of this paper is to explain the contemporary mental health legislation in our
      country the Republic of Macedonia and the problems with the implementation of
      involuntary hospitalisation. This could be overcome with close cooperation
      between the judicial and health care system.

PMID- 27703576
TI  - Characterization and Cytotoxicity Analysis of a Ciprofloxacin Loaded
      Chitosan/Bioglass Scaffold on Cultured Human Periodontal Ligament Stem Cells: a
      Preliminary Report.
AB  - AIM: The aim of this study was to analyze the cytotoxicity of ciprofloxacin (CIP)
      loaded on chitosan bioactive glass scaffold on human periodontal ligament stem
      cells (PLSCs) in vitro. MATERIALS AND METHODS: PLSCs obtained from human third
      molars, cultures treated with medium containing 15 x 15 mm chitosan/bioactive
      glass scaffolds without/with different concentration 0, 5, 10, and 20 % of CIP. A
      total of 15 x 10^3 cells were plated in 6 well plates. The attached cells of each
      group were harvested from the plates after 1, 4 and 8 days of culture to detect
      the viability of cells. The cell number was determined using a hemocytometer and
      the trypan blue dye-exclusion assay. Data was analyzed using normality using
      Shapiro-Wilk test. Comparisons between groups were made using One-way ANOVA
      complemented by Tukey's test. RESULTS: When comparing the proliferation rate of
      cells in the four groups, no statistically significant difference was found (P =
      0.633). With regards to cell viability, no statistical difference was found
      between the 0, 5, and 10 % CIP concentrations, while the 20 % CIP concentration
      demonstrated the least viability with a high statistically significant difference
      (P = 0.003). CONCLUSION: Twenty percentages CIP demonstrated the least
      proliferation rate and viability.

PMID- 27703577
TI  - Midfacial Reconstruction - A Systematic Review.
AB  - AIM: Different lesions affecting the midfacial regions require surgical
      reconstruction. The aim of this study was to assess the different methods used in
      midfacial reconstruction after maxillectomy procedures. The various reported
      surgical reconstructive techniques focusing on the esthetic and functional
      outcomes are to be reviewed in this article. MATERIAL AND METHODS: A thorough
      PUBMED and hand-search of journals of relevance was performed on related terms
      and yielded 772 titles of which 45 abstracts were selected and obtained as full
      articles for further evaluation while the rest were excluded by title/abstract.
      According to the inclusion criteria; 14 of these studies were used to complete
      this article. RESULTS: In this review we showed that fibular and radial
      vascularized grafts were the most commonly reported methods in literature with a
      few other options. Computer aided design and surgical planning has been also
      reviewed and seems to be a rapidly evolving option for maxillofacial
      reconstruction. Lack of RCTs (randomized controlled trials) and large scale case
      series was noticed in this review making the evidence of poor quality.
      CONCLUSION: Methods of evaluation of reconstruction options mainly qualitative
      and subjective made the evaluation of the techniques in this review difficult.

PMID- 27703578
TI  - A Comparative Clinical Study of the Effect of Denture Cleansing on the Surface
      Roughness and Hardness of Two Denture Base Materials.
AB  - AIM: This study aimed to verify the influence of oral environment and denture
      cleansers on the surface roughness and hardness of two different denture base
      materials. METHODS: A total of sixteen identical removable disc specimens (RDS)
      were processed. Eight RDS were made from heat-cured acrylic resin (AR) and the
      other eight were fabricated from thermoplastic injection moulded resin (TR).
      Surface roughness and hardness of DRS were measured using ultrasonic profilometry
      and Universal testing machine respectively. Then the four RDS (two AR and two of
      TR) were fixed to each maxillary denture, after three months RDS were retrieved.
      Surface roughness and hardness of RDS have measured again. RESULTS: The surface
      roughness measurements revealed no significant difference (p >0.05) for both disc
      groups at baseline. However, both groups showed a significant increase in the
      surface roughness after three months with higher mean value for (TR) group. On
      the other hand, the (AR) group showed higher hardness mean value than (TR) group
      at baseline with no significant decrease in the hardness values (p >0.05)
      following three months follow-up period. CONCLUSIONS: Denture cleansers have an
      effect on the denture's surface roughness and hardness concurrently with an oral
      condition which will consequently influence the complete dentures' lifetime and
      patients' satisfaction.

PMID- 27703579
TI  - A Comparative Study of Transbuccal and Extraoral Approaches in the Management of
      Mandibular Angle Fractures: A Systematic Review.
AB  - AIM: The aim of the present study was to compare the extraoral and transbuccal
      approaches for the treatment of mandibular angle fractures with regard to
      postoperative complications. PATIENTS AND METHODS: An electronic search for
      relevant articles without language and date restrictions was performed in July
      2016. Inclusion criteria were studies in humans including randomised controlled
      trials (RCTs), controlled clinical trials (CCTs), prospective studies (PS), and
      retrospective studies (RS). In total, 107 patients were included from four
      studies (transbuccal = 48, extraoral = 59). The follow-up period varied from 3
      months to 24 months. RESULTS: In extraoral group the average of unsightly scar,
      facial nerve weakness, infection, malocclusion, plate removal were found to be
      55% (range, 10% -100%), 26.5% (range, 0%-53%), 11.7% (range, 0% - 20%), 22.5%
      (range, 0% -50%), 6.7% (range, 3.3% - 10%) respectively while these parameters in
      the transbuccal approach were found to be no obvious unsightly scar, 6.6 %
      (range, 0%-13.3%), 8.1% (range, 0% - 20%), 4.8% (range, 0% - 12.5%), 0%. The
      incidence of postoperative trismus and nonunion/malunion were 0% in both groups.
      CONCLUSION: The results of this study suggest that transbuccal approach shows
      fewer complications than extraoral approach when used for the treatment of
      mandibular angle fractures.

PMID- 27703580
TI  - Managing the Cutaneous Sinus Tract of Dental Origine.
AB  - BACKGROUND: Draining cutaneous sinus tract in chin area may be caused by chronic
      periapical dental infections. Misdiagnosis of these lesions usually leads to
      destructive invasive treatment of the sinus tract that is not correct and
      curative. CASE REPORT: A 31-year-old male patient referred to us with a
      chronically draining lesion on his chin. The lesion previously was misdiagnosed
      by medical doctors and had undergone two times surgery with a focus on the skin
      lesion and had received antibiotic therapy for a prolonged period of time. After
      clinical and radiologic examination the dental origin of the lesion was evident
      and proper endodontic and surgical treatment was performed. Three months later,
      after the treatment, the lesion showed total healing and reoccurrence occurred.
      CONCLUSION: The key to successful treatment of cutaneous sinus tract of dental
      origin must be in appropriate communication between the dentist and the physician
      in order to achieve correct diagnosis and therapy in such cases.

PMID- 27703581
TI  - Allostatic Load Assessment for Early Detection of Stress in the Workplace in
      Egypt.
AB  - AIM: Workplace stress is hazardous for its harmful impact on employees' health
      and organizational productivity. The aim of the study is to apply the Allostatic
      Load Index (ALI) which is a multi-component measure for health risk assessment
      and early detection of stress among workers in Egypt. METHODS: Sixty-two working
      adults randomly selected from two different working environments in Egypt were
      included in the study. Participants completed a self-reported questionnaire for
      socio-demographic and work variables. Andrews and Withey test for Job
      Satisfaction was filled and 3 ml blood samples were collected. Markers assessed
      for Allostatic Load were serum cortisol, c-reactive protein,
      dehydroepiandrosterone-sulphate, total thyroxine, total cholesterol,
      triglycerides, low-density lipoprotein, high-density lipoprotein, total
      cholesterol to high-density lipoprotein ratio, systolic and diastolic blood
      pressures, waist to hip ratio and body mass index. The risk quartile method was
      used for calculation of ALI. ALI value of four or more indicates high Allostatic
      Load. RESULTS: Job satisfaction scale defined about a quarter of the study
      population (24%) to be dissatisfied with Allostatic Load of 2.4 as the mean
      value. Population percentage with ALI >=4 reached 12.9% with 100% of them
      females. A significant association was found between Allostatic Load of primary
      mediators and age, the presence of chronic diseases, place of work and female
      gender. CONCLUSION: Female gender and the old age of the Egyptian workforce under
      study are at higher risk of chronic diseases. Using an alternative way -for
      example, the cut-point method- instead of the risk quartiles for dichotomization
      of markers used in ALI calculation could be more precise for early detection of
      stress among healthy individuals.

PMID- 27703582
TI  - Analysis of Marketing Strategy for Food Supplements and Over-The-Counter
      Medicines.
AB  - Marketing strategy is correlated with the regulations for the corresponding
      product category. Accordingly, there is a big difference in the marketing
      strategy of food supplements and over-the-counter medicines. In this paper are
      presented 2 different marketing strategies of a new small pharmaceutical company
      in two studies. The findings of studies analysis can be used for developing
      marketing strategies in the wider sense and other products, for other small to
      medium sized companies in other countries of interest with similar regulations
      and help them understand how to position and promote themselves and their
      products.

PMID- 27703583
TI  - A Worksite Health Education Workshop as Empowerment Intervention for Health
      Promotion in the National Research Centre of Egypt.
AB  - AIM: The study aimed to assess worksite health education workshops as a
      successful tool for health promotion of employees. MATERIAL AND METHODS: A one
      day workshop was held for individuals engaged in research activities in the
      National research Centre of Egypt at the worksite. Its main objective was to
      highlight the nature, causes, symptoms and management of job stress. Participants
      were asked to fill a personality assessment sheet, a self-reported questionnaire
      for job satisfaction. Other questionnaires for assessment of falsification of
      type and some socio-demographic data were filled by the attendants. A concise
      survey was introduced at the end of the workshop for feedback collection.
      RESULTS: Attendants of the workshop were 36 subjects mainly females (94.4%). Mean
      age was 40.5 years with 63.9% of participants at their postdoctoral studies
      stage. Participants were at midway in the scale of job satisfaction (3.3) and did
      not suffer from falsification (0.3). The feedback survey score (11.5) showed
      great acceptance for the intervention. Special interest in the topic of stress
      was reported by 35.1% of attendants who found it the best item in the workshop
      and the interactive manipulation came next as declared by 18.9% of the
      participants. CONCLUSION: Worksite health education workshops seem to be a
      successful practice for empowerment in the Egyptian workplace.

PMID- 27703585
TI  - Etiopathogenesis of Differentiated Thyroid Carcinomas.
AB  - INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting
      of most frequent differentiated encountered carcinomas, papillary and follicular
      thyroid carcinoma, then medullary thyroid carcinoma originating from
      neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas
      arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly
      differentiated anaplastic thyroid carcinoma. There are increasing numbers of
      epidemiological studies and publications that have suggested increased incidence
      rate of thyroid carcinomas. We have read, analysed and compare available reviews
      and original articles investigating different etiological factors in the
      development of thyroid carcinomas through Google Scholar and PubMed Database.
      DISCUSSION: Aetiology involved in the development of thyroid carcinomas is
      multifactorial and includes external influences, as well as constitutional
      predispositions and genetic etiological factors. The actual effect of
      environmental and constitutional factors is on promoting genetic and epigenetic
      alterations which result in cell proliferation and oncogenesis. Until now are
      identified numerous genetic alterations, assumed to have an important role in
      oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating
      growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION:
      This new molecular insight could have a crucial impact on diagnosis and also on
      improving and selecting an appropriate treatment to the patients with thyroid
      malignancies.

PMID- 27703586
TI  - Venous Thromboembolism - Current Diagnostic and Treatment Modalities.
AB  - BACKGROUND: Pulmonary embolism and deep venous thrombosis, known as venous
      thromboembolism (VTE), are associated with a high proportion of morbidity and
      mortality. AIM: Aim of this review is to emphasise current diagnostic and
      therapeutic modalities for VTE. RESULTS: No differences have been noticed in
      European and American guidelines in diagnostic approach of this disorder. Today
      there is enough clinical information for the use of heparin (either,
      unfractionated or low molecular) and vitamin K antagonists in the treatment of
      acute and chronic phases of VTE. Novel oral anticoagulants seem to have some
      advantages in the treatment of this disorder. Rivaroxaban has been approved
      widespread, for use as a single-drug approach of VTE. CONCLUSION: Both guidelines
      are almost similar and good basis for evidence-based treatment of this disorder.

PMID- 27703584
TI  - The Role of Levosimendan in Patients with Decreased Left Ventricular Function
      Undergoing Cardiac Surgery.
AB  - The postoperative low cardiac output is one of the most important complications
      following cardiac surgery and is associated with increased morbidity and
      mortality. The condition requires inotropic support to achieve adequate
      hemodynamic status and tissue perfusion. While catecholamines are utilised as a
      standard therapy in cardiac surgery, their use is limited due to increased oxygen
      consumption. Levosimendan is calcium sensitising inodilatator expressing positive
      inotropic effect by binding with cardiac troponin C without increasing oxygen
      demand. Furthermore, the drug opens potassium ATP (KATP) channels in cardiac
      mitochondria and in the vascular muscle cells, showing cardioprotective and
      vasodilator properties, respectively. In the past decade, levosimendan
      demonstrated promising results in treating patients with reduced left ventricular
      function when administered in peri- or post- operative settings. In addition, pre
      operative use of levosimendan in patients with severely reduced left ventricular
      ejection fraction may reduce the requirements for postoperative inotropic
      support, mechanical support, duration of intensive care unit stay as well as
      hospital stay and a decrease in post-operative mortality. However, larger studies
      are needed to clarify clinical advantages of levosimendan versus conventional
      inotropes.

PMID- 27703587
TI  - An Updated Mini Review of Vitamin D and Obesity: Adipogenesis and Inflammation
      State.
AB  - Vitamin D related research continues to expand and theorise regarding its
      involvement in obesity, as both hypovitaminosis D and obesity strike in pandemic
      proportions. Vitamin D plays an important role in immune system through Vitamin D
      Receptors (VDR), which are transcription factors located abundantly in the body.
      Due to this characteristic, it is potentially linked to obesity, which is a state
      of inflammation involving the release of cytokines from adipose tissue, and
      exerting stress on other organs in a state of positive energy balance. Research
      trials in the past couple of years and systematic reviews from SCOPUS and MEDLINE
      will be discussed. The role of Vitamin D throughout the lifespan (from fetal
      imprinting until older age), and in various other obesity mediated chronic
      conditions shall be highlighted. Various mechanisms attributed to the inverse
      relationship of Vitamin D and obesity are discussed with research gaps
      identified, particularly the role of adipokines, epigenetics, calcium and type of
      adipose tissue.

PMID- 27703588
TI  - How to Verify and Manage the Translational Plagiarism?
AB  - The use of Google translator as a tool for determining translational plagiarism
      is a big challenge. As noted, plagiarism of the original papers written in
      Macedonian and translated into other languages can be verified after computerised
      translation in other languages. Attempts to screen the translational plagiarism
      should be supported. The use of Google Translate tool might be helpful. Special
      focus should be on any non-English reference that might be the source of
      plagiarised material and non-English article that might translate from an
      original English article, which cannot be detected by simple plagiarism screening
      tool. It is a hard job for any journal to detect the complex translational
      plagiarism but the harder job might be how to effectively manage the case.

PMID- 27703589
TI  - Particle rotational trapping on a floating electrode by rotating induced-charge
      electroosmosis.
AB  - We describe a novel rotating trait of induced-charge electroosmotic slip above a
      planar metal surface, a phenomenon termed "Rotating induced-charge electro
      osmosis" (ROT-ICEO), in the context of a new microfluidic technology for tunable
      particle rotation or rotational trap. ROT-ICEO has a dynamic flow stagnation line
      (FSL) that rotates synchronously with a background circularly polarized electric
      field. We reveal that the rotating FSL of ROT-ICEO gives rise to a net
      hydrodynamic torque that is responsible for rotating fluids or particles in the
      direction of the applied rotating electric field either synchronously or
      asynchronously, the magnitude of which is adjusted by a balance between rotation
      of FSL and amplitude of angular-direction flow component oscillating at twice the
      field frequency. Supported by experimental observation, our physical
      demonstration with ROT-ICEO proves invaluable for the design of flexible
      electrokinetic framework in modern microfluidic system.

PMID- 27703590
TI  - Sheathless electrokinetic particle separation in a bifurcating microchannel.
AB  - Particle separation has found practical applications in many areas from industry
      to academia. Current electrokinetic particle separation techniques primarily rely
      on dielectrophoresis, where the electric field gradients are generated by either
      active microelectrodes or inert micro-insulators. We develop herein a new type of
      electrokinetic method to continuously separate particles in a bifurcating
      microchannel. This sheath-free separation makes use of the inherent wall-induced
      electrical lift to focus particles towards the centerline of the main-branch and
      then deflect them to size-dependent flow paths in each side-branch. A theoretical
      model is also developed to understand such a size-based separation, which
      simulates the experimental observations with a good agreement. This electric
      field-driven sheathless separation can potentially be operated in a parallel or
      cascade mode to increase the particle throughput or resolution.

PMID- 27703592
TI  - Amplitude modulation schemes for enhancing acoustically-driven
      microcentrifugation and micromixing.
AB  - The ability to drive microcentrifugation for efficient micromixing and particle
      concentration and separation on a microfluidic platform is critical for a wide
      range of lab-on-a-chip applications. In this work, we investigate the use of
      amplitude modulation to enhance the efficiency of the microcentrifugal
      recirculation flows in surface acoustic wave microfluidic systems, thus
      concomitantly reducing the power consumption in these devices for a given
      performance requirement-a crucial step in the development of miniaturized,
      integrated circuits for true portable functionality. In particular, we show that
      it is possible to obtain an increase of up to 60% in the acoustic streaming
      velocity in a microdroplet with kHz order modulation frequencies due to the
      intensification in Eckart streaming; the streaming velocity is increasing as the
      modulation index is increased. Additionally, we show that it is possible to
      exploit this streaming enhancement to effect improvements in the speed of
      particle concentration by up to 70% and the efficiency of micromixing by 50%,
      together with a modest decrease in the droplet temperature.

PMID- 27703591
TI  - Development of an advanced microfluidic micropipette aspiration device for single
      cell mechanics studies.
AB  - Various micro-engineered tools or platforms have been developed recently for cell
      mechanics studies based on acoustic, magnetic, and optical actuations. Compared
      with other techniques for single cell manipulations, microfluidics has the
      advantages with simple working principles and device implementations. In this
      work, we develop a multi-layer microfluidic pipette aspiration device integrated
      with pneumatically actuated microfluidic control valves. This configuration
      enables decoupling of cell trapping and aspiration, and hence causes less
      mechanical perturbation on trapped single cells before aspiration. A high
      trapping efficiency is achieved by the microfluidic channel design based on fluid
      resistance model and deterministic microfluidics. Compared to conventional
      micropipette aspiration, the suction pressure applied on the aspirating cells is
      highly stable due to the viscous nature of low Reynolds number flow. As a proof
      of-concept of this novel microfluidic technology, we built a microfluidic pipette
      aspiration device with 2 * 13 trapping arrays and used this device to measure the
      stiffness of a human breast cancer cell line, MDA-MB-231, through the observation
      of cell deformations during aspiration. As a comparison, we studied the effect of
      Taxol, a FDA-approved anticancer drug on single cancer cell stiffness. We found
      that cancer cells treated with Taxol were less deformable with a higher Young's
      modulus. The multi-layer microfluidic pipette aspiration device is a scalable
      technology for single cell mechanophenotyping studies and drug discovery
      applications.

PMID- 27703593
TI  - Physical characterization of nanoparticle size and surface modification using
      particle scattering diffusometry.
AB  - As the field of colloidal science continues to expand, tools for rapid and
      accurate physiochemical characterization of colloidal particles will become
      increasingly important. Here, we present Particle Scattering Diffusometry (PSD),
      a method that utilizes dark field microscopy and the principles of particle image
      velocimetry to measure the diffusivity of particles undergoing Brownian motion.
      PSD measures the diffusion coefficient of particles as small as 30 nm in diameter
      and is used to characterize changes in particle size and distribution as a
      function of small, label-free, surface modifications of particles. We demonstrate
      the rapid sizing of particles using three orders-of-magnitude less sample volume
      than current standard techniques and use PSD to quantify particle uniformity.
      Furthermore, PSD is sensitive enough to detect biomolecular surface modifications
      of nanometer thickness. With these capabilities, PSD can reliably aid in a wide
      variety of applications, including colloid sizing, particle corona
      characterization, protein footprinting, and quantifying biomolecule activity.

PMID- 27703594
TI  - Capillary flow of blood in a microchannel with differential wetting for blood
      plasma separation and on-chip glucose detection.
AB  - We report capillary flow of blood in a microchannel with differential wetting for
      the separation of a plasma from sample blood and subsequent on-chip detection of
      glucose present in a plasma. A rectangular polydimethylsiloxane microchannel with
      hydrophilic walls (on three sides) achieved by using oxygen plasma exposure
      enables capillary flow of blood introduced at the device inlet through the
      microchannel. A hydrophobic region (on all four sides) in the microchannel
      impedes the flow of sample blood, and the accumulated blood cells at the region
      form a filter to facilitate the separation of a plasma. The modified wetting
      property of the walls and hence the device performance could be retained for a
      few weeks by covering the channels with deionised water. The effects of the
      channel cross-section, exposure time, waiting time, and location and length of
      the hydrophobic region on the volume of the collected plasma are studied. Using a
      channel cross-section of 1000 * 400 MUm, an exposure time of 2 min, a waiting
      time of 10 min, and a hydrophobic region of width 1.0 cm located at 10 mm from
      the device inlet, 450 nl of plasma was obtained within 15 min. The performance of
      the device was found to be unaffected (provides 450 nl of plasma in 15 min) even
      after 15 days. The purification efficiency and plasma recovery of the device were
      measured and found to be comparable with that obtained using the conventional
      centrifugation process. Detection of glucose at different concentrations in whole
      blood of normal and diabetic patients was performed (using 5 MUl of sample blood
      within 15 min) to demonstrate the compatibility of the device with integrated
      detection modules.

PMID- 27703596
TI  - Enoxaparin-Induced Skin Necrosis.

PMID- 27703595
TI  - Microvessel manifold for perfusion and media exchange in three-dimensional cell
      cultures.
AB  - Integrating a perfusable microvasculature system in vitro is a substantial
      challenge for "on-chip" tissue models. We have developed an inclusive on-chip
      platform that is capable of maintaining laminar flow through porous biosynthetic
      microvessels. The biomimetic microfluidic device is able to deliver and generate
      a steady perfusion of media containing small-molecule nutrients, drugs, and gases
      in three-dimensional cell cultures, while replicating flow-induced mechanical
      stimuli. Here, we characterize the diffusion of small molecules from the
      perfusate, across the microvessel wall, and into the matrix of a 3D cell culture.

PMID- 27703597
TI  - A study on usefulness of a set of known risk factors in predicting maternal
      syphilis infections in three districts of Western Province, Zambia.
AB  - INTRODUCTION: Despite roll-out of cost-effective point-of-care tests, less than
      half antenatal attendees in rural western Zambia are screened for syphilis. This
      study formulated a clinical, risk-based assessment criteria and evaluated its
      usefulness as a non-biomedical alternative for identifying high-risk prenatal
      cases. METHODS: We conducted a cross-sectional survey of antenatal clinic
      attendees in Kaoma, Luampa and Nkeyema districts to collect data on exposure to
      nine pre-selected syphilis risk factors. These factors were classified into major
      and minor factors based on their observed pre-study association strengths to
      maternal syphilis. Clinical disease was defined as exposure to either two major
      factors, one major with two minor factors or three minor factors. Sensitivity,
      specificity and predictive values of the clinical protocol were then calculated
      in comparison to rapid plasmin reagin results. RESULTS: The observed syphilis
      prevalence was 9.3% (95% CI: 7.4 - 11.6%) and the overall sensitivity of the
      study criteria was 62.3% with positive predictive value of 72.9%. Sensitivities
      of individual case-defining categories were even lower; from 17.4% to 33.3%.
      Results confirmed that abortion history, still birth, multiple sexual partners,
      previous maternal syphilis infection, partner history of sexually transmitted
      infection and maternal co-morbid conditions of HIV and genital ulcer disease were
      significantly associated to maternal syphilis in study population as well.
      CONCLUSION: The criteria was not as effective as biomedical tests in identifying
      maternal syphilis. However, it could be a useful adjunct/alternative in antenatal
      clinics when biomedical tests are either inadequate or unavailable.

PMID- 27703598
TI  - Cognitive function in Nigerian children with newly diagnosed epilepsy: a
      preliminary report.
AB  - INTRODUCTION: Epilepsy has long been associated with cognitive dysfunction and
      educational underachievement. The purpose of the study was to describe the
      baseline findings from a larger prospective study. METHODS: New cases of epilepsy
      aged 6-16 years seen at a paediatric neurology clinic in Ibadan, Nigeria were
      evaluated for any evidence of cognitive impairment. Intelligence quotient (IQ) of
      the participants was measured using the Wechsler Intelligence Scale for Children
      Fourth Edition (WISC-IV). Scores on cognitive subtests and Full Scale IQ (FSIQ)
      were computed and association between the subsets scores and seizure variables
      were calculated. RESULTS: 40 children, 24 males and 16 females were studied and
      their ages ranged from 6 to 16 years with a mean of 10.8 (SD=3.0) years. Global
      intellectual functioning as measured by the WISC-IV was in the normal range (FSIQ
      scores <85) for 52.5% (n = 21) of the participants and the remaining participants
      (47.5%) scored between the borderline and severe category for intellectual
      disability. The strongest correlation was between 'caregiver's assessment of
      school performance' and FSIQ, (r = 0.70; p< 0.001). Age at onset of epilepsy and
      seizure type had no significant association with scores on the WISC-IV composite
      scores. CONCLUSION: There is a high prevalence of significant cognitive
      dysfunction in Nigerian children with epilepsy, even in the absence of any known
      brain insult. All children with epilepsy should have routine IQ assessment
      following diagnosis, in order to allow for early intervention when indicated, and
      thus, improved outcomes.

PMID- 27703599
TI  - Antioxidant-Enhancing Property of the Polar Fraction of Mangosteen Pericarp
      Extract and Evaluation of Its Safety in Humans.
AB  - Crude extract from the pericarp of the mangosteen (mangosteen extract [ME]) has
      exhibited several medicinal properties in both animal models and human cell
      lines. Interestingly, the cytotoxic activities were always observed in nonpolar
      fraction of the extract whereas the potent antioxidant was often found in polar
      fraction. Although it has been demonstrated that the polar fraction of ME
      exhibited the antioxidant activity, the safety of the polar fraction of ME has
      never been thoroughly investigated in humans. In this study, we investigated the
      safety of oral administration of the polar fraction of ME in 11 healthy Thai
      volunteers. During a 24-week period of the study, only minor and tolerable side
      effects were reported; no serious side effects were documented. Blood chemistry
      studies also showed no liver damage or kidney dysfunction in all subjects. We
      also demonstrated antioxidant property of the polar fraction of ME both in vitro
      and in vivo. Interestingly, oral administration of the polar fraction of ME
      enhanced the antioxidant capability of red blood cells and decreased oxidative
      damage to proteins within red blood cells and whole blood.

PMID- 27703600
TI  - Cholesterol Retards Senescence in Bone Marrow Mesenchymal Stem Cells by
      Modulating Autophagy and ROS/p53/p21Cip1/Waf1 Pathway.
AB  - In the present study, we demonstrated that bone marrow mesenchymal stem cells
      (BMSCs) of the 3rd passage displayed the senescence-associated phenotypes
      characterized with increased activity of SA-beta-gal, altered autophagy, and
      increased G1 cell cycle arrest, ROS production, and expression of p53 and
      p21Cip1/Waf1 compared with BMSCs of the 1st passage. Cholesterol (CH) reduced the
      number of SA-beta-gal positive cells in a dose-dependent manner in aging BMSCs
      induced by H2O2 and the 3rd passage BMSCs. Moreover, CH inhibited the production
      of ROS and expression of p53 and p21Cip1/Waf1 in both cellular senescence models
      and decreased the percentage of BMSCs in G1 cell cycle in the 3rd passage BMSCs.
      CH prevented the increase in SA-beta-gal positive cells induced by RITA
      (reactivation of p53 and induction of tumor cell apoptosis, a p53 activator) or 3
      MA (3-methyladenine, an autophagy inhibitor). Our results indicate that CH not
      only is a structural component of cell membrane but also functionally contributes
      to regulating cellular senescence by modulating cell cycle, autophagy, and the
      ROS/p53/p21Cip1/Waf1 signaling pathway.

PMID- 27703601
TI  - In vitro evaluation of efficacy of different rotary instrument systems for gutta
      percha removal during root canal retreatment.
AB  - BACKGROUND: Complete removal of old filling material during root canal
      retreatment is fundamental for predictable cleaning and shaping of canal anatomy.
      Most of the retreatment methods tested in earlier studies have shown inability to
      achieve complete removal of root canal filling. Therefore the aim of this
      investigation was to assess the efficacy of three different rotary nickel
      titanium retreatment systems and Hedstrom files in removing filling material from
      root canals. MATERIAL AND METHODS: Sixty extracted mandibular premolars were
      decoronated to leave 15 mm root. Specimen were hand instrumented and obturated
      using gutta percha and AH plus root canal sealer. After storage period of two
      weeks, roots were retreated with three (Protaper retreatment files, Mtwo
      retreatment files, NRT GPR) rotary retreatment instrument systems and Hedstroem
      files. Subsequently, samples were sectioned longitudinally and examined under
      stereomicroscope. Digital images were recorded and evaluated using Digital Image
      Analysing Software. The retreatment time was recorded for each tooth using a
      stopwatch. The area of canal and the residual filling material was recorded in
      mm2 and the percentage of remaining filling material on canal walls was
      calculated. Data was analysed using ANOVA test. RESULTS: Significantly less
      amount of residual filling material was present in protaper and Mtwo instrumented
      teeth (p < 0.05) compared to NRT GPR and Hedstrom files group. Protaper
      instruments also required lesser time during removal of filling material followed
      by Mtwo instruments, NRT GPR files and Hedstrom files. CONCLUSIONS: None of the
      instruments were able to remove the filling material completely from root canal.
      Protaper universal retreatment system and Mtwo retreatment files were more
      efficient and faster compared to NRT GPR fles and Hedstrom files. Key words:Gutta
      percha removal, nickel titanium, root canal retreatment, rotary instruments.

PMID- 27703603
TI  - Effectiveness of Amlexanox and Adcortyl for the treatment of recurrent aphthous
      ulcers.
AB  - BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common condition that
      affects approximately 20% of the general population. The ulcers can interfere
      with speech and eating and cause significant pain and discomfort. This study
      aimed to evaluate the efficacy of Amlexanox and Adcortyl in the treatment of
      aphthous ulcers. MATERIAL AND METHODS: In this randomized double blind clinical
      trial with sequential patient entry, a total of 40 patients who presented with
      aphthous ulcers were included. Patients were received Amlexanox or Adcortyl four
      times daily for 7 days. Patients were evaluated for pain, lesion size, and
      tingling at one day, three days, five days and seven days follow-ups. The
      treatment effects were then evaluated using the Wilcoxon-Mann-Whitney (WMW) test.
      Values of p<0.05 were considered significant. RESULTS: No significant differences
      in pain score, tingling and lesion size were observed on similar days between
      Amlexanox and Adcortyl groups. In both groups, reduction in the assessed
      variables was significant between days 1-3, 3-5, and 5-7 (p < 0.001).
      CONCLUSIONS: This study indicated that Amlexanox as well as Adcortyl was
      effective in relieving pain and reducing the lesion size during the treatment of
      aphthous ulcers. Key words:Recurrent aphthous stomatitis, Amlexanox, Adcortyl,
      pain relief.

PMID- 27703602
TI  - Danger zone analysis using cone beam computed tomography after apical enlargement
      with K3 and K3XF in a manikin model.
AB  - BACKGROUND: The objective of the study was to evaluate and compare how apical
      enlargement with K3 and K3XF nickel-titanium (NiTi) rotary instruments reduces
      the root thickness in the danger zone and affects canal transportation and
      centering ability in mandibular molar mesial canals in a manikin extracted tooth
      model. MATERIAL AND METHODS: Seventy-two mesial root canals of first mandibular
      molars were instrumented. Initial and post-instrumentation Cone Beam Computed
      Tomography scans were performed after root canal preparation up to size 25, 30,
      35 and 40 files. Canal transportation, canal centering and remaining root dentin
      thickness toward the danger zone were calculated in sections 1, 2 and 3 mm under
      the furcation level. Data were analyzed using non-parametric Kruskal-Wallis
      analysis of variance at a significance level of P < 0.05. RESULTS: K3 instruments
      removed more dentin toward the danger zone compared with K3XF instruments (P<
      .05) and significant differences in dentin thickness were found when canal
      enlargement was performed to a #35-40 with both systems (P< 0.05). No significant
      differences in canal transportation and centering ability were found between
      systems, except when canal enlargement was performed to a #40 (P = 0,0136). No
      differences were observed when comparing the number of uses in both systems (P>
      0.05). CONCLUSIONS: Under the conditions of this study K3 removed a significant
      amount of dentin at the furcation level compared with the R-Phase K3XF rotary
      system in curved root canals. Enlargement to a 35-40/04 file removed
      significantly more dentin with both systems. Key words:K3, K3XF, R-phase, center
      ability, canal transportation, dentin thickness, increased apical enlargement,
      danger zone, dentin thickness.

PMID- 27703604
TI  - Effect of pre-heating on the mechanical properties of silorane-based and
      methacrylate-based composites.
AB  - BACKGROUND: The use of composites in dental restoration has been commonly
      criticized, due to their underwhelming mechanical properties. This problem may be
      solved partially by preheating. The present research aims to determine the effect
      of preheating on the mechanical properties of two different classes of
      composites. MATERIAL AND METHODS: A Silorane-based (Silorane) and a Methacrylate
      based (Z250) composite were preheated to different temperatures (25, 37, and 68 
      degrees C) and afterwards were tested with the appropriate devices for each
      testing protocol. The material's flexural strength, elastic modulus, and Vickers
      microhardness were evaluated. Two-way ANOVA, and Tukey's post hoc were used to
      analyze the data. RESULTS: Microhardness and elastic modulus increased with
      preheating, while flexural strength values did not increase significantly with
      preheating. Furthermore the methacrylate-based composite (Z250) showed higher
      values compared to the Silorane-based composite (Silorane) in all the tested
      properties. CONCLUSIONS: Preheating Silorane enhances the composite's
      microhardness and elastic modulus but does not affect its flexural strength. On
      the other hand, preheating Z250 increases its microhardness but does not change
      its flexural strength or elastic modulus. In addition, the Z250 composite shows
      higher microhardness and flexural strength than Silorane, but the elastic modulus
      values with preheating are similar. Therefore Z250 seems to have better
      mechanical properties making it the better choice in a clinical situation. Key
      words:Composite, elastic modulus, flexural strength, microhardness, preheating.

PMID- 27703605
TI  - Awareness of droplet and airborne isolation precautions among dental health
      professionals during the outbreak of corona virus infection in Riyadh city, Saudi
      Arabia.
AB  - BACKGROUND: This study aimed to determine knowledge, attitude and practice of
      airborne and droplet isolation precautions among Dental Health Professionals
      (DHPs) (dental students, interns, practitioners and auxiliaries) during the
      outbreak of MERS (Middle East Respiratory Syndrome), corona virus infection in
      Riyadh city, Saudi Arabia. MATERIAL AND METHODS: A cross-sectional survey was
      conducted among 406 dental health professionals (DHPs) working in selected dental
      facilities in Riyadh city, Saudi Arabia during the outbreak of MERS (April-June
      2013). A structured, close-ended, self-administered questionnaire explored the
      knowledge, attitude, and practice towards droplet and isolation precautions.
      Collected data was subjected to descriptive statistics to express demographic
      information, mean knowledge score, mean attitude score and practice score of
      DHPs. Inferential statistics (Mann-Whitney U test and Kruskal Wallis tests, p <
      0.05) were used to examine differences between study variables. Spearman's rho
      correlation was used to identify the association between the knowledge-attitude,
      knowledge-practice, and attitude-practice. RESULTS: A response rate of rate of
      90.22% (406 out of 452) was obtained. The mean scores of knowledge, attitude and
      practice were 10.61 +/- 1.19, 50.54 +/- 7.53 and 8.50 +/- 2.14 respectively.
      Spearman's correlation test revealed a significant linear positive correlation
      between knowledge and attitude (r-0.501, P- 0.01), knowledge and practice (r
      0.185, P-0.01) and attitude and practice (r-0.351, P- 0.01) of DHPs about
      airborne isolation precautions. CONCLUSIONS: Dental health professionals
      considered in the present study showed good knowledge, positive attitude and good
      practice towards droplet and airborne isolation precautions during outbreak of
      MERS. Key words:Knowledge, attitude, practice, droplet, airborne, precaution,
      dental professionals.

PMID- 27703607
TI  - Assessment of non-carious root surface defects in areas of gingival recession: A
      descriptive study.
AB  - BACKGROUND: The purpose of this descriptive study was to observe the distribution
      of four different classes of non-carious cervical root surface discrepancies in
      teeth with gingival recession. Additionally to explore the different treatment
      modalities in the literature for each of these defects. MATERIAL AND METHODS: A
      total of 150 subjects with at least one labial gingival recession were included
      in the study. 1400 teeth were evaluated using 2.5 X magnification loupes and UNC 
      15 probe for the presence of the cemento-enamel junction and step like defects
      according to Pini-Prato's classification: A-, identifiable CEJ without defect;
      A+, identifiable CEJ with defect; B-, unidentifiable CEJ without defect, B+,
      unidentifiable CEJ with defect. Further a comprehensive electronic and hand
      search of pubmed indexed journals was performed to identify appropriate treatment
      modalities for these defects and their predictability following
      restorative/surgical or combination of both. RESULTS: A total of 1400 teeth with
      exposed root surfaces were examined (793 Maxillary; 607 mandibular). 499 teeth
      were A-, 405 were A+, 322 were B+ and 174 were B-. The distribution of these
      defects in different teeth was: 36% premolars, 32% molars, 21% incisors and 11%
      canines, collectively 68% in the aesthetic zone. CONCLUSIONS: Majority of these
      lesions are in the maxillary aesthetic zone. Hence the presence of the CEJ and
      the defect must be taken into account while managing these defects surgically.
      Key words:Cervical abrasion, gingival recession, magnification loupes, root
      coverage, step defects.

PMID- 27703606
TI  - In vitro histological evaluation of the surgical margins made by different laser
      wavelengths in tongue tissues.
AB  - BACKGROUND: Lasers have become standard tools for the surgical treatment of oral
      lesions. The purpose of this study is to determine the surgical margins and
      histologically evaluate the tissue thermal effects induced by different types of
      surgical instruments. MATERIAL AND METHODS: Cuts were made in pork tongues'
      mucosa with different lasers (Er:YAG at 2W with and without air / water spray and
      at 4W with and without air / water spray; CO2 at 3.5W and 7W in pulsed mode and
      at 7W in continuous mode; the diode laser at 3.5W and boost 3.5W in pulsed mode;
      Nd:YAG at 6W, 40Hz and electroscalpel at 5W and conventional scalpel as control.
      Macroscopic and microscopic morphological changes were evaluated. RESULTS: The
      results of this study showed that the surgical instruments that caused greater
      tissue damage extension were: the Nd:YAG laser (670.68MUm), the diode 3.5W and
      boost PW (626.82MUm), the CO2 7W CW (571.18MUm), the CO2 at 7W PW (485.45MUm),
      the diode 3.5W PW (456.15MUm), the electroscalpel (409.57MUm) and lastly the CO2
      laser 3.5W PW (306.19MUm) and Er:YAG (74.66MUm) laser, regardless of power, mode
      or air / water spray used. An association between the Tissue Damage Extension and
      the Degree of Carbonization (r = 0.789; P = 0.01), and an association between the
      Tissue Damage Extension and Regularity of the Incision were found (r = -, 299; P
      = 0.01). CONCLUSIONS: The results of this study suggest that lasers can be used
      in soft tissues biopsies of the oral cavity, enabling a correct histopathological
      analysis, as long as the biological effects of each laser type are considered.
      The Er:YAG laser revealed its potential for biopsies of the oral mucosa ensuring
      a successful histological evaluation and the CO2 laser at 3,5W in pulsed mode
      presented itself as the best choice for surgeries with hemostasis. Key words:CO2
      laser, diode laser, Er:YAG laser, laser surgery, Nd:YAG laser, oral mucosa,
      thermal effect.

PMID- 27703608
TI  - Arch width changes in patients with Class II division 1 malocclusion treated with
      maxillary first premolar extraction and non-extraction method.
AB  - BACKGROUND: The aim of this study was to determine arch width changes during
      maxillary first premolars extraction and non-extraction treatment in patients
      with Class II division 1 malocclusion. MATERIAL AND METHODS: Dental casts of 91
      Class II division 1 patients (36 males and 55 females) were evaluated. The
      minimum age of the subjects at the beginning of treatment was above 16 years. 48
      patients were treated with extraction of the maxillary first premolars and 43
      patients were treated without extraction. Pre- and post-treatment maxillary and
      mandibular inter-canine and inter-molar arch widths were measured. RESULTS: At
      the end of treatment, maxillary and mandibular inter-canine widths of both groups
      increased significantly. The maxillary inter-molar width decreased in the
      extraction group and increased in the non-extraction group. The mandibular inter
      molar width increased significantly in both groups. No significant differences
      were observed between males and females. CONCLUSIONS: The results of this study
      indicated that there was a tendency for an increase in arch width during both the
      extraction and non-extraction treatment except maxillary inter-molar width in the
      extraction cases. Key words:Dental arch, malocclusion, angle Class II, tooth
      movement, extraction.

PMID- 27703609
TI  - Does hybridized dentin affect bond strength of self-adhesive resin cement?
AB  - BACKGROUND: Evaluate the influence of different hybridization bonding techniques
      of a self-adhesive resin cement. MATERIAL AND METHODS: 30 human health molars
      were divided into six groups (n=10). The specimens received three longitudinal
      sections, allowing insertion of central cuts in PVC matrices. Each group received
      a different dentin pretreatment according to the manufacturer's recommendations,
      except the control group (G1), as follows. G2 - a 3-step total-etch adhesive
      system (OptibondTM FL, Kerr); G3 - a 3-step total-etch adhesive system (AdperTM
      ScotchbondTM Multi-Purpose, 3M ESPE); G4 - a 2-step total-etch adhesive system
      (AdperTM Single Bond 2, 3M ESPE); G5 - a single-step self-etching system (Bond
      Force, Tokuyama); and G6 - universal bonding system (Single Bond Universal, 3M
      ESPE). Then, cylinders made of self-adhesive resin cement with polypropylene
      matrix was cemented in all groups (RelyX U200, 3M ESPE). Bond strength was
      assessed by submitting the specimens to micro-shear test and was characterized
      according to the fracture pattern observed through optical microscopy. RESULTS:
      The results were submitted to the Kruskal-Wallis test, which indicated a
      statistically significant difference between the groups (p=0.04), and Tukey's
      multiple comparisons, which indicated a statistically significant difference
      between G1 and G3 (p<0.05). The microscopic analysis revealed a high prevalence
      of adhesive failures, followed by mixed fractures, and cohesive failures in the
      dentin. CONCLUSIONS: The use of a previous dentin hybridization protocol is able
      to increase adhesive bonding resistance of self-adhesive resin cement, especially
      when used AdperTM ScotchbondTM Multi-Purpose system. Key words:Bonding, self
      adhesive resin cement, adhesive systems, microshear.

PMID- 27703610
TI  - Silver nanoparticles in resin luting cements: Antibacterial and physiochemical
      properties.
AB  - BACKGROUND: Silver has a long history of use in medicine as an antimicrobial and
      anti-inflammatory agent. Silver nanoparticles (NAg) offer the possibility to
      control the formation oral biofilms through the use of nanoparticles with
      biocidal, anti-adhesive, and delivery abilities. This study aims to evaluate the
      antibacterial effect of resin luting cements with and without NAg, and their
      influence on color, sorption and solubility. MATERIAL AND METHODS: NAg were
      incorporated to two dual-cured resin cements (RelyX ARC (RA) color A1 and RelyX
      U200 (RU) color A2) in two concentrations (0.05% and 0.07%, in weight), obtaining
      six experimental groups. Disc specimens (1x6mm) were obtained to verify the
      antibacterial effect against Streptococcus mutans in BHI broth after immersion
      for 1min, 5min, 1h, 6h, and 24h (n=3), through optical density readings.
      Specimens were evaluated for color changes after addition of NAg with a
      spectrophotometer (n=10). Sorption and solubility tests were also performed,
      considering storage in water or 75% ethanol for 28 days (n=5), according to ISO
      4049:2010. Data were subjected to statistical analysis with ANOVA and Tukey
      (p=0.05). RESULTS: The optical density of the culture broths indicated bacterial
      growth, with and without NAg. NAg produced significant color change on the resin
      cements, especially in RA. Solubility values were very low for all groups, while
      sorption values raised with NAg. The cements with NAg did not show antibacterial
      activity against S. mutans. They also showed perceptible color change and higher
      sorption than the materials without NAg. CONCLUSIONS: The resin luting cements
      with NAg addition did not show antibacterial activity against SS. mutans. They
      also showed perceptible color change and higher sorption than the materials
      without NAg. Key words:Silver, resin cements, products with antimicrobial action,
      solubility, color perception tests.

PMID- 27703611
TI  - Are different generations of CAD/CAM milling machines capable to produce
      restorations with similar quality?
AB  - BACKGROUND: Different CAD/CAM machines' generation may impact the restoration
      overall quality. The present study evaluated the marginal fit of CAD/CAM
      restorations manufactured with different generations of CEREC milling unit
      systems. MATERIAL AND METHODS: Sixteen typodont teeth were divided into two
      groups (n=8) according to the machine's generation assigned. These are control
      group (G1): Cerec AC with Bluecam/Cerec 3 milling unit and (G2): Cerec AC with
      Bluecam/MC XL Premium Package milling unit. Scanning of the preparation were
      performed and crowns were milled using the Vita Mark II blocks. Blocks were
      cemented using epoxy glue on the pulpal floor only and finger pressure applied
      for 1 min. Upon completion of the cementation step, misfits between the
      restoration and abutment were measured by microphotography and the silicone
      replica technique using light body silicon material on Mesial (M) and Distal (D)
      surfaces. RESULTS: Mean and SDs of marginal gaps in micrometers were: G1/M: 94.90
      (+/-38.52), G1/D: 88.53 (+/-44.87), G2/M: 85.65 (+/-29.89), G2/D: 95.28 (+/
      28.13). Two-way ANOVA indicated no significant differences among different groups
      (P>0.05); surface area (P>0.05) and the interaction (P>0.05). Overall, G2 had
      greater margin gaps than G1, however, without statistical difference (P>0.05).
      CONCLUSIONS: Difference in milling unit generation did not significantly affect
      the marginal fit. Marginal gap means were in the range of the clinical acceptance
      levels for both generations of Cerec milling units, regardless the teeth site
      area. Key words:CAD/CAM, margin, ceramics.

PMID- 27703613
TI  - In vitro comparison of passive and continuous ultrasonic irrigation in curved
      root canals.
AB  - BACKGROUND: The efficacy of endodontic irrigation procedures can be compromised
      by the complexity of the root canal system. Delivering irrigants to the apical
      third of curved canals presents a particular challenge to endodontists. This
      study compared the effects of two ultrasonic irrigation techniques on the
      penetration of sodium hypochlorite into the main canal and simulated lateral
      canals of curved roots in extracted teeth. MATERIAL AND METHODS: Two sets of
      simulated lateral canals were created at 2, 4, and 6 mm from the working length
      in 60 single-rooted teeth (6 canals/tooth, n = 360 canals). The teeth were
      randomly divided into three experimental irrigation groups: group 1 (n = 20),
      positive pressure irrigation (PPI); group 2 (n = 20), passive ultrasonic
      irrigation (PUI); and group 3 (n = 20), continuous ultrasonic irrigation (CUI).
      To assess the irrigation solution penetration, 20% Chinese ink (Sanford Rotring
      GmbH, Hamburg, Germany) was added to a 5% sodium hypochlorite solution and
      delivered into the curved root canals. The penetration of contrast solution into
      the simulated lateral canals was scored by counting the number of lateral canals
      (0-2) penetrated to at least 50% of the total length. RESULTS: The CUI group
      showed significantly higher (P < 0.05) irrigant penetration into the lateral
      canals and into the apical third of the main canals. The PPI group showed
      significantly lower sodium hypochlorite penetration (P < 0.001) into the main and
      lateral canals compared with that in the CUI and PUI groups. Significantly higher
      irrigant penetration was observed in the PUI group than the PPI group.
      CONCLUSIONS: Using CUI as the final rinse significantly increased the penetration
      of irrigant solution into the simulated lateral canals and apical third of curved
      roots. Key words:Continuous ultrasonic irrigation, curved root canals, passive
      ultrasonic irrigation, positive pressure irrigation, root canal irrigation.

PMID- 27703612
TI  - Occurrence and timing of complications following traumatic dental injuries: A
      retrospective study in a dental trauma department.
AB  - BACKGROUND: This study explores the pattern of complications occurrence resulting
      from traumatic dental injuries, the relation of this pattern to the number of
      years from the time of the injury to its first diagnosis, and other contributing
      characteristics such as root development and trauma characteristic. MATERIAL AND
      METHODS: Patients' data treated following dental trauma from 2002 to 2014 were
      classified and grouped according to age, gender, tooth type, injury type,
      diagnosis and the time that elapsed between the traumatic event and the diagnosis
      of complications (TIC). The distribution function of the quantitative parameters
      was determined with the Kolmogorov-Smirnov test. Fisher exact test was used to
      test differences between categorical parameters. RESULTS: The review identified
      166 patients (114 male and 52 female), with a total of 287 traumatized teeth, and
      a mean of 1.8 injured teeth per incident. Maxillary teeth were involved
      significantly more often in traumatic dental injuries. The follow-up period range
      (TIC) had a mean of 2.99 years. The most frequent complication was pulp necrosis
      (34.2%). The most frequent complication related to avulsion was ankylotic root
      resorption (50%) diagnosed after a median TIC of 1.18 years. Open apices at the
      occurrence of trauma were observed in 52 teeth. Of these, 54.9% experienced pulp
      necrosis and 9.8% inflammatory root resorption with a median TIC of 1.63 years.
      Teeth that experienced multiple traumatic events showed significantly more late
      pulp necrosis compared to teeth that experienced a single traumatic injury (61.9%
      vs. 25.3%, respectively, p<0.0001). CONCLUSIONS: Follow-up periods should be
      based on the type of traumatic dental injury and the severity of the potential
      complications for the tooth. Current recommendations for follow-up after
      traumatic dental injury should be revised to reflect the need for more frequent
      and overall prolonged follow-up. Key words:Dental trauma, avulsion, open apex,
      pulp necrosis, root resorption, follow-up, complications.

PMID- 27703614
TI  - Comparative efficacy of aloe vera mouthwash and chlorhexidine on periodontal
      health: A randomized controlled trial.
AB  - BACKGROUND: With introduction of many herbal medicines, dentistry has recently
      evidenced shift of approach for treating many inflammatory oral diseases by using
      such modalities. Aloe vera is one such product exhibiting multiple benefits and
      has gained considerable importance in clinical research recently. AIM: To compare
      the efficacy of Aloevera and Chlorhexidine mouthwash on Periodontal Health.
      MATERIAL AND METHODS: Thirty days randomized controlled trial was conducted among
      390 dental students. The students were randomized into two intervention groups
      namely Aloe Vera (AV) chlorhexidine group (CHX) and one control (placebo) group.
      Plaque index and gingival index was recorded for each participant at baseline, 15
      days and 30 days. The findings were than statistically analyzed, ANOVA and Post
      Hoc test were used. RESULTS: There was significant reduction (p<0.05) in the mean
      scores of all the parameters with Aloe Vera (AV) and chlorhexidine group. Post
      hoc test showed significant difference (p<0.000) in mean plaque and gingival
      index scores of aloe Vera and placebo and chlorhexidine and placebo group. No
      significant difference (p<0.05) was observed between AloeVera and chlorhexidine
      group. CONCLUSIONS: Being an herbal product AloeVera has shown equal
      effectiveness as Chlorhexidine. Hence can be used as an alternative product for
      curing and preventing gingivitis. Key words:Aloe vera, chlorhexidine, dental
      plaque, gingivitis.

PMID- 27703615
TI  - Clinical value of diascopy and other non-invasive techniques on differential
      diagnosis algorithms of oral pigmentations: A systematic review.
AB  - OBJECTIVES: To determine the diagnostic value of diascopy and other non-invasive
      clinical aids on recent differential diagnosis algorithms of oral mucosal
      pigmentations affecting subjects of any age. MATERIAL AND METHODS: Data Sources:
      this systematic review was conducted by searching PubMed, Scopus, Dentistry &
      Oral Sciences Source and the Cochrane Library (2000-2015); Study Selection: two
      reviewers independently selected all types of English articles describing
      differential diagnosis algorithms of oral pigmentations and checked the
      references of finally included papers; Data Extraction: one reviewer performed
      the data extraction and quality assessment based on previously defined fields
      while the other reviewer checked their validity. RESULTS: Data Synthesis: eight
      narrative reviews and one single case report met the inclusion criteria. Diascopy
      was used on six algorithms (66.67%) and X-ray was included once (11.11%; 44.44%
      with text mentions); these were considered helpful tools in the diagnosis of
      intravascular and exogenous pigmentations, respectively. Surface rubbing was
      described once in the text (11.11%). CONCLUSIONS: Diascopy was the most applied
      method followed by X-ray and surface rubbing. The limited scope of these
      procedures only makes them useful when a positive result is obtained, turning
      biopsy into the most recommended technique when diagnosis cannot be established
      on clinical grounds alone. Key words:Algorithm, differential diagnosis, flow
      chart, oral mucosa, oral pigmentation, systematic review.

PMID- 27703616
TI  - Accidental displacement of a dental implant into the sublingual space: A Case
      report.
AB  - Dental implant surgery is continuously expanding. In fact, every day more and
      more surgeons are choosing dental implants for allowing great results in the
      field of oral rehabilitation. However, these procedures are not exempt from
      complications. This report presents the case of a 66 years old man underwent
      implant surgery by a specialized dentist. No problems were reported during
      implant placement. Despite this, three months later, it was displaced into the
      sublingual space at the time of uncovering. Against this backdrop, the patient
      was referred to an expert maxillofacial surgeon. Next day, the implant was
      removed using an intraoral approach to reach the sublingual space. According with
      our knowledge, there are no cases reported in the literature that describe this
      complication. Key words:Dental implant, sublingual space, bone atrophy,
      complications of oral surgery.

PMID- 27703617
TI  - Stunted root development: A rare dental complication of Stevens-Johnson syndrome.
AB  - Stevens-Johnson syndrome (SJS) is a severe cutaneous reaction seen rarely in
      clinical practice. Most often, it occurs as an adverse reaction to certain drugs.
      When it affects children at a very young age, arrested tooth root development may
      also be seen. We present a case of a 13 year old boy who suffered from SJ
      syndrome at the age of 7 years. Incomplete root development was observed in all
      teeth, as demonstrated by panaromic radiography. Clinical features of this
      condition and its management are further discussed. We aim to emphasise on the
      need for dental practitioners to be aware of the potential dental complications
      of SJS and enable them to recognise and manage the condition at the earliest so
      as to avoid any undesirable sequelae. Key words:Adverse drug reaction,
      amoxycillin, arrested root development, Stevens-Johnson syndrome.

PMID- 27703618
TI  - Mandibular destructive radiolucent lesion: The first sign of multiple myeloma.
AB  - The occurrence of a mandibular lesion as the first sign of multiple myeloma (MM)
      is uncommon. This report describes a case of MM diagnosed because of a mandibular
      lesion. A 62-year-old woman presented a destructive radiolucent lesion in the
      right mandibular ramus. The lesion caused rupture of the anterior cortical bone
      and extended from the retromolar area to the coronoid process. An incisional
      biopsy was performed. Histopathological examination revealed numerous pleomorphic
      plasma cells, some with binucleated nuclei. The tumor cells showed kappa light
      chain restriction. Bone marrow biopsy showed findings of massive infiltration of
      neoplastic plasma cells, besides lesions in the vertebrae. The diagnosis of MM
      was established. The patient underwent autologous hematopoietic stem-cell
      transplantation. Currently, the patient is under regular follow up after 40
      months of initial treatment. In conclusion, MM should be considered in the
      differential diagnosis of destructive mandibular lesions. Key words:Mandible,
      multiple myeloma, radiolucent lesion.

PMID- 27703619
TI  - Meningitis and subdural empyema as complication of pterygomandibular space
      abscess upon tooth extraction.
AB  - Complication of dental infections might be various and heterogeneous. The most
      common complications are represented by maxilar celulitis, canine space
      celulitis, infratemporal space celulitis, temporal celulitis and bacteremia.
      Among rarest complications we found: sepsis, bacterial endocarditis,
      mediastinitis, intracranial complications, osteomyelitis, etc. Although dental
      infections are often considered trivial entities, sometimes they can reach an
      impressive gravity. In this regard, the present study describes a case of dental
      infection complicated by meningitis, subdural empiema and cerebral vasculitis.
      Furthermore, we observed other neurological complications, like thalamic ischemic
      infarction, during the disease evolution. Noteworthy, these entities were not
      presented when the patient was admitted to hospital. Therefore, the main aim of
      this report is to highlight the serious consequences that an infection of dental
      origin could cause. Key words:Meningitis, subdural empyema, odontogenic
      infections.

PMID- 27703620
TI  - Multidisciplinary surgical management of Cowden syndrome: Report of a case.
AB  - Cowden's Syndrome (CS) is a rare congenital autosomal dominant disorder that
      affects around 1/200000 patients with an incomplete penetrance and variable
      expressivity, characterized by alterations in a tumor suppressor gene. A 14-year
      old Caucasian male patient came to the attention of the authors complaining of
      palm nodules, gingival bleeding and painful pedunculated lesions on the lips and
      on the labial side of anterior sextants. After genetic investigation the final
      diagnosis of a Cowden Syndrome was made. The lesions were surgically removed
      under general anesthesia and no clinical signs of recurrence were found three
      months after surgical excision. Considering the severe symptoms of the syndrome
      and the strong tendency to malignant development of the associated lesions all
      clinicians should focus their efforts to the early diagnosis and, when possible,
      multidisciplinary treatment. Key words:Early diagnosis, multiple hamartoma
      syndrome, oral papillomatosis, cancer predisposition, case report.

PMID- 27703621
TI  - Sugammadex: watch out for new side effects.

PMID- 27703622
TI  - A first step toward understanding patient safety.
AB  - Patient safety has become an important policy agenda in healthcare systems since
      publication of the 1999 report entitled "To Err Is Human." The paradigm has
      changed from blaming the individual for the error to identifying the weakness in
      the system that led to the adverse events. Anesthesia is one of the first
      healthcare specialties to adopt techniques and lessons from the aviation
      industry. The widespread use of simulation programs and the application of human
      factors engineering to clinical practice are the influences of the aviation
      industry. Despite holding relatively advanced medical technology and comparable
      safety records, the Korean health industry has little understanding of the
      systems approach to patient safety. Because implementation of the existing system
      and program requires time, dedication, and financial support, the Korean
      healthcare industry is in urgent need of developing patient safety policies and
      putting them into practice to improve patient safety before it is too late.

PMID- 27703623
TI  - How to understand and conduct evidence-based medicine.
AB  - Evidence-based medicine (EBM) is the conscientious, explicit, and judicious use
      of current best evidence in making decisions regarding the care of individual
      patients. This concept has gained popularity recently, and its applications have
      been steadily expanding. Nowadays, the term "evidence-based" is used in numerous
      situations and conditions, such as evidence-based medicine, evidence-based
      practice, evidence-based health care, evidence-based social work, evidence-based
      policy, and evidence-based education. However, many anesthesiologists and their
      colleagues have not previously been accustomed to utilizing EBM, and they have
      experienced difficulty in understanding and applying the techniques of EBM to
      their practice. In this article, the author discusses the brief history,
      definition, methods, and limitations of EBM. As EBM also involves making use of
      the best available information to answer questions in clinical practice, the
      author emphasizes the process of performing evidence-based medicine: generate the
      clinical question, find the best evidence, perform critical appraisal, apply the
      evidence, and then evaluate. Levels of evidence and strength of recommendation
      were also explained. The author expects that this article may be of assistance to
      readers in understanding, conducting, and evaluating EBM.

PMID- 27703624
TI  - Dexmedetomidine combined with midazolam vs. dexmedetomidine alone for sedation
      during spinal anesthesia.
AB  - BACKGROUND: Dexmedetomidine is a useful sedative agent for spinal anesthesia.
      However, it has been reported that dexmedetomidine decreases heart rate in a dose
      dependent manner. In the current study, we compared the administration of a bolus
      dose of midazolam and bolus loading of dexmedetomidine over 10 min with the goal
      of identifying an additional method of sedation. METHODS: Ninety patients
      classified as American Society of Anesthesiologists physical status I-II who were
      undergoing spinal anesthesia were divided into two groups. In the midazolam and
      dexmedetomidine combined group (group MD), 10 min after bolus loading of 0.05
      mg/kg midazolam, 0.5 ug/kg/h dexmedetomidine was continuously infused. In the
      dexmedetomidine group (group D), 1 ug/kg dexmedetomidine was infused over 10 min,
      and then 0.5 ug/kg/h dexmedetomidine was continuously infused. RESULTS: At 10
      min, the sedation depth of the two groups was almost equal. In both groups, the
      bispectral index was within the optimal score range of 55-80 and the Ramsay
      Sedation Scale score was within the optimal range of 3-5. Satisfaction with
      sedation for both patient and surgeon did not differ between the two groups. At
      10 min, heart rate was significantly lower (P < 0.010) in group D and mean blood
      pressure was significantly lower (P < 0.010) in group MD. The prevalence of
      bradycardia, hypotension, and hypoxia did not differ statistically between the
      two groups (P = 0.714, P = 0.089, P = 0.495, respectively). CONCLUSIONS:
      Midazolam bolus and dexmedetomidine continuous infusion (the regimen of group MD)
      may be an additional sedation method for patients who have severe bradycardia.

PMID- 27703625
TI  - Effective doses of cisatracurium in the adult and the elderly.
AB  - BACKGROUND: There are few information about the differences of the effective dose
      (ED) of cisatracurium between the adult and the elderly. We investigated the ED
      and the onset time of cisatracurium in the adults and the elderly. METHODS: We
      studied two hundred patients of the adults aged 20 through 64 years and the
      elderly aged >= 65 years, with American Society of Anesthesiologists physical
      status I or II. Each 100 patients with 20 patients of each dose group, randomly
      selected from 30, 40, 50, 60 or 70 ug/kg of cisatracurium, were randomly
      allocated to the adults and the elderly groups. We recorded the 0.1 Hz single
      twitch responses of the adductor pollicis and the onset times to maximal
      blockade. The magnitude of muscle relaxation was recorded by using an
      acceleromyography. The effect of cisatracurium on single twitch was calculated as
      percent reduction. After converting each drug dose into logarithm and percent
      reduction of the muscle reduction into probit, the EDs representing the muscle
      relaxation effects of 5%, 25%, 50%, 75% and 95% were estimated using the linear
      regression analysis. RESULTS: No significant differences were found in age,
      weight, height, or body mass index within or between the groups. The ED50 and
      ED95 of the adult group were 35.39 and 59.58 ug/kg. The ED50 and ED95 of the
      elderly group were 34.89 and 55.50 ug/kg, respectively. The onset times were
      375.4 +/- 76.9 seconds in the adult group and 369.1 +/- 70.0 seconds in the
      elderly group. CONCLUSIONS: The ED and the onset time were not significantly
      different between the adult and the elderly.

PMID- 27703626
TI  - Impact of hydroxyethyl starch 70/0.5 on acute kidney injury after
      gastroenterological surgery.
AB  - BACKGROUND: Previous studies reported a higher mortality risk and a greater need
      for renal replacement therapy in patients administered hydroxyethyl starch (HES)
      rather than other fluid resuscitation preparations. In this study, we
      investigated the association between 6% HES 70/0.5 use and postoperative acute
      kidney injury (AKI) in gastroenterological surgery patients. METHODS: We
      conducted retrospective full-cohort and propensity-score-based analyses of
      patients who underwent gastroenterological surgery between June 2011 and August
      2013 in a Japanese university hospital. The study sample comprised 66 AKI and
      2,152 non-AKI patients in the full-cohort analysis and 35 AKI and 1,269 non-AKI
      patients in the propensity-score-based analysis. Propensity scores were
      calculated using an ordered logistic regression model in which the dependent
      variable comprised three groups based on HES infusion volumes (0, 1-999, and >=
      1,000 ml). The association between HES groups and postoperative AKI incidence was
      analyzed using multiple logistic regression models. Other candidate independent
      variables included patient characteristics and intraoperative measures. RESULTS:
      In the full-cohort analysis, 40 (60.6%) AKI patients were diagnosed as "risk", 15
      (22.7%) as "injury," and 11 (16.7%) as "failure". In the propensity-score-based
      analysis, the corresponding values were 22 (62.9%), 8 (22.9%), and 5 (14.3%).
      There was no significant association between total infused HES and postoperative
      AKI incidence in either the full-cohort or the propensity-score-based analysis (P
      = 0.168 and P = 0.42, respectively). CONCLUSIONS: AKI incidence was not
      associated with clinical 6% HES 70/0.5 administration in gastroenterological
      surgery patients treated at a single center.

PMID- 27703627
TI  - Pretreatmet with 5% lidocaine patch reduces cannula-induced and propofol-induced
      pain: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: The purpose of this study was to determine the efficacy of 5%
      lidocaine patch in reducing propofol-induced pain and cannula-induced pain.
      METHODS: In a randomized, double-blind study, 126 patients were divided into one
      of three groups: pretreatment with a 5% lidocaine patch (Lidotop(r)) and premixed
      2 ml of normal saline with 1.5 mg/kg of 1% propofol (Group A); pretreatment with
      a placebo patch and premixed 2 ml of normal saline with 1.5 mg/kg of 1% propofol
      (Group B); or pretreatment with a placebo patch and premixed 2 ml of 2% lidocaine
      (40 mg) with 1.5 mg/kg of 1% propofol (Group C) for induction of anesthesia. Pain
      severity was evaluated on a four-point verbal rating scale during intravenous
      cannulation, propofol injection, and 24 h after the operation (recall). RESULTS:
      Eighteen patients (47.4%) in Group A complained of cannula-induced pain compared
      with 35 (94.6%) in Group B and 36 (94.7%) in Group C (P < 0.001). Group A
      patients showed significantly lower incidence of propofol-induced pain and recall
      of propofol-induced pain compared with Group B (P < 0.001 and P = 0.01), whereas
      there was no difference compared with Group C. CONCLUSIONS: Preoperative
      transdermal administration of 5% lidocaine patch is an effective and simple
      method in reducing propofol-induced pain as well as cannula-induced pain.

PMID- 27703628
TI  - Ultrasound measurement of the vertebral level of Tuffier's line in elderly women.
AB  - BACKGROUND: It would be imprecise to generalize the vertebral level determined by
      palpation to patients of all ages. The purpose of this study was to compare the
      vertebral level passed by Tuffier's line in elderly women with that passed in
      adult women using ultrasound in the left lateral decubitus flexed position.
      METHODS: We enrolled 50 female patients over the age of 65 (elderly group) and 50
      female patients between ages 20 and 50 (control group) who had been scheduled to
      undergo spinal anesthesia. Using ultrasound, we marked the L2-5 lumbar spinous
      processes and intervertebral spaces. The most cephalad part was labeled 1 and the
      most caudal part was labeled 11. We then identified which line of these vertebral
      levels Tuffier's line crossed. RESULTS: The median value of the numbers
      signifying the vertebral level of Tuffier's line was 3 (the L2-3 intervertebral
      space) in the elderly group, while it was 8 (the lower part of the L4 vertebra)
      in the control group. The vertebral level of Tuffier's line had statistically
      significant correlations with age, body mass index, and weight in the elderly
      group (P < 0.001). CONCLUSIONS: The vertebral level of Tuffier's line determined
      with ultrasound measurement in the left lateral decubitus flexed position was
      more cephalad in the elderly women than in those of the control group. Therefore,
      we should consider that the needle could be inserted at a higher level than
      expected, and use care in determining the level of needle insertion during spinal
      anesthesia in elderly women.

PMID- 27703629
TI  - Comparison of effects of intraoperative nefopam and ketamine infusion on managing
      postoperative pain after laparoscopic cholecystectomy administered remifentanil.
AB  - BACKGROUND: Although intraoperative opioids provide more comfortable anesthesia
      and reduce the use of postoperative analgesics, it may cause opioid induced
      hyperalgesia (OIH). OIH is an increased pain response to opioids and it may be
      associated with N-methyl-D-aspartate (NMDA) receptor. This study aimed to
      determine whether intraoperative nefopam or ketamine, known being related on NMDA
      receptor, affects postoperative pain and OIH after continuous infusion of
      intraoperative remifentanil. METHODS: Fifty-four patients undergoing laparoscopic
      cholecystectomy were randomized into three groups. In the nefopam group (N
      group), patients received nefopam 0.3 mg/kg at the induction of anesthesia
      followed by a continuous infusion of 0.065 mg/kg/h. In the ketamine group (K
      group), patients received ketamine 0.3 mg/kg at the induction of anesthesia
      followed by a continuous infusion of 3 ug/kg/min. The control group did not
      received any other agents except for the standard anesthetic regimen.
      Postoperative pain score, first time and number of demanding rescue analgesia,
      OIH and degrees of drowsiness/sedation scale were examined. RESULTS: Co
      administrated nefopam or ketamine significantly reduced the total amount of
      intraoperative remifentanil and postoperative supplemental morphine. Nefopam
      group showed superior property over control and ketamine group in the
      postoperative VAS score and recovery index (alertness and respiratory drive),
      respectively. Nefopam group showed lower morphine consumption than ketamine
      group, but not significant. CONCLUSIONS: Both nefopam and ketamine infusion may
      be useful in managing in postoperative pain control under concomitant infusion of
      remifentanil. However, nefopam may be preferred to ketamine in terms of sedation.

PMID- 27703630
TI  - Operation room management in Korea: results of a survey.
AB  - BACKGROUND: The current state of general hospital operation room (OR) in Korea
      and how these ORs are being operated remain unclear. Therefore, the aim of this
      study was to investigate and assess the current state of OR management and
      surgical scheduling in general hospitals of Korea. METHODS: A total of 92
      anesthesiology training hospitals and 2 equivalent hospitals in Korea were
      targeted for the survey. Anesthesiologists in hospitals received questionnaires
      for OR, anesthetic managements and surgical scheduling directly or by phone from
      the beginning of October 2015 to the end of December 2015. RESULTS: Of the 94
      hospitals that were targeted, 59 hospitals (62.7%) responded to the survey. Of
      the 59 hospitals, 40 (67.8%) had 500-1,000 beds, 36 (61.0%) had 11-20 ORs. Most
      OR arrangements were made by residents and specialists in Anesthesiology
      Department (90%). Most hospitals (47.4%) in the response set performed total
      surgeries in the range of 10,000 to 20,000 annually. The proportion of emergency
      surgeries in the total surgeries was 2.8-55.0%. Methods for predicting expected
      surgery time were arbitrarily decided by surgeons (61%), anesthesiologist's
      experience (20%), or by analyzing historical data using software (5%).
      CONCLUSIONS: This survey study could trigger active operational researches for OR
      efficiency. It might help hospital policy makers manage OR resources more
      efficiently.

PMID- 27703632
TI  - A comparison of strength for two continuous peripheral nerve block catheter
      dressings.
AB  - BACKGROUND: Despite the benefits of continuous peripheral nerve blocks, catheter
      dislodgment remains a major problem, especially in the ambulatory setting.
      However, catheter dressing techniques to prevent such dislodgment have not been
      studied rigorously. We designed this simulation study to test the strength of two
      commercially available catheter dressings. METHODS: Using a cadaver model, we
      randomly assigned 20 trials to one of two dressing techniques applied to the
      lateral thigh: 1) clear adhesive dressing alone, or 2) clear adhesive dressing
      with an anchoring device. Using a digital luggage scale attached to a loop
      secured by the dressing, the same investigator applied steadily increasing force
      with a downward trajectory towards the floor until the dressing was removed or
      otherwise disrupted. RESULTS: The weight, measured (median [10th-90th
      percentile]) at the time of dressing disruption or removal, was 1.5 kg (1.3-1.8
      kg) with no anchoring device versus 4.9 kg (3.7-6.5 kg) when the dressing
      included an anchoring device (P < 0.001). CONCLUSIONS: Based on this simulation
      study, using an anchoring device may help prevent perineural catheter
      dislodgement and therefore premature disruption of continuous nerve block
      analgesia.

PMID- 27703631
TI  - Development of the Geop-Pain questionnaire for multidisciplinary assessment of
      pain sensitivity.
AB  - BACKGROUND: To assess the multidisciplinary aspects of pain, various self-rating
      questionnaires have been developed, but there have not been sufficient relevant
      studies on this topic in South Korea. The aim of this study was to develop a new
      pain sensitivity-related questionnaire in the Korean language that would be
      simple and would well reflect Koreans' senses. METHODS: A new pain assessment
      questionnaire was developed through a pre-survey on "geop", which is the Korean
      word expressing fear, anxiety, or catastrophizing. We named the new assessment
      questionnaire the Geop-Pain Questionnaire (GPQ). The GPQ was composed of 15 items
      divided into three categories and rated on a 5-point scale. As a preliminary
      study, internal consistency and test-retest reliability analyses were conducted.
      Subsequently, 109 individuals completed the GPQ along with three pain-related
      questionnaires translated into Korean (Pain Sensitivity Questionnaire [PSQ], Pain
      Anxiety Symptoms Scale [PASS], and Pain Catastrophizing Scale [PCS]), and the
      correlations were analyzed. RESULTS: All items in the GPQ showed appropriate
      internal consistency, and the test-retest reliability analysis showed no
      statistically significant differences. The correlations between the GPQ and the
      existing questionnaires revealed that the GPQ scores had mid-positive
      correlations with the PSQ scores and strong positive correlations with the PASS
      and PCS scores. CONCLUSIONS: This study attempted to develop a questionnaire
      assessing pain sensitivity multidimensionally using the Korean word geop for the
      first time. The self-rating GPQ showed high correlations with the existing
      questionnaires and demonstrated potential to be utilized as a pain prediction
      index in clinical practice.

PMID- 27703633
TI  - Anaphylactic shock caused by intramuscular injection of midazolam during the
      perioperative period: a case report.
AB  - Although anaphylactic shock during the perioperative period is rare, it can be
      lethal due to severe cardiovascular and respiratory collapse. Midazolam is
      generally used as premedication for relieving anxiety about the operation, and
      the danger of anaphylactic shock after intramuscular injection is not widely
      recognized. We report the first case of anaphylactic shock occurring during the
      perioperative period after intramuscular injection of midazolam. Since
      anaphylactic shock after intramuscular injection can be of slow onset, the
      operation should be delayed if an anaphylactic reaction is suspected, even if the
      symptoms are limited. In addition, anesthesiologists should be prepared for the
      occurrence of anaphylaxis at any time in the perioperative period.

PMID- 27703634
TI  - Cardiac arrest after sugammadex administration in a patient with variant angina:
      a case report.
AB  - A 76-year-old man with no notable medical history was scheduled for a robot
      assisted radical prostatectomy. After the operation, he was given sugammadex. Two
      minutes later, ventricular premature contraction bigeminy began, followed by
      cardiac arrest. Cardiac arrest occurred three times and cardiopulmonary
      resuscitation was done. The patient recovered after the third cardiopulmonary
      resuscitation and was transferred to the intensive care unit. Coronary
      angiography was done on postoperative day 1. The patient was diagnosed with
      variant angina and discharged uneventfully on postoperative day 8.

PMID- 27703635
TI  - Anesthetic management during surgery for left ventricular aneurysm and false
      aneurysm occurring in stage: a case report.
AB  - Left ventricular aneurysm (LVA) and false aneurysm are complications of acute
      myocardial infarction, trauma, and cardiac surgery. Left ventricular false
      aneurysm (LVFA) is a particularly catastrophic complication owing to its high
      propensity for rupture. Surgical resection should be considered for LVFA
      occurring within three months after myocardial infarction or development of
      congestive heart failure. In this report, we describe a case of acute heart
      failure with LVA and LVFA occurring in stage as a complication of myocardial
      infarction in a 55-year-old man. The patient was also at risk of brain ischemia
      due to abnormal vessel status and a previous cerebrovascular accident with left
      sided weakness. Successful perioperative anesthetic management was achieved by
      focusing on maintaining marginal upper normal blood pressure to ensure cerebral
      perfusion and to reduce the risk of false aneurysm rupture.

PMID- 27703636
TI  - Bronchoscopic concerns in Proteus syndrome: a case report.
AB  - Proteus syndrome (PS) is a rare congenital hamartomatous disorder with
      multisystem involvement. PS shows highly clinical variability due to overgrowth
      of the affected areas, and several features can make anesthetic management
      challenging. Little is known about the airway problem associated with anesthesia
      in PS patients. An 11-year-old girl with PS was scheduled for ear surgery under
      general anesthesia. She had features complicating intubation including facial
      asymmetry and disproportion, abnormal teeth, limitation of neck movement due to
      torticollis, and thoracolumbar scoliosis. This study reports on a case of
      deformed airway of a PS patient under fiberoptic bronchoscopy.

PMID- 27703637
TI  - Intracranial hemorrhage induced uncontrolled seizure in a deceased donor liver
      transplant patient: a case report.
AB  - Seizure is the second most common neurologic complication after liver
      transplantation and may be caused by metabolic abnormalities, electrolyte
      imbalance, infection, and immunosuppressant toxicity. A 61-year-old male patient
      underwent liver transplantation due to hepatitis B virus-related liver cirrhosis
      with portal systemic encephalopathy. The immediate postoperative course of the
      patient was uncomplicated. However, on postoperative day (POD) 6, weakness
      developed in both lower extremities. No abnormal findings were detected on a
      brain computed tomography (CT) scan on POD 8, but a generalized tonic clonic
      seizure developed which was difficult to control even with multiple antiepileptic
      drugs. A follow-up brain CT scan on POD 15 showed a 2.7 cm sized acute
      intracranial hemorrhage (ICH) in the left parietal lobe. The patient's mental
      status improved after 2 months and he was able to communicate through eye
      blinking or head shaking. Our case reports an acute ICH that manifested into a
      refractory seizure in a patient who underwent a liver transplant.

PMID- 27703638
TI  - Central venous catheter malposition due to dialysis catheter: a case report.
AB  - A 56-year-old man on maintenance hemodialysis was admitted to the intensive care
      unit with septic shock and coagulopathy. As there was a dialysis catheter in the
      right internal jugular vein, the left internal jugular vein was cannulated with a
      central venous catheter to initiate vasopressor therapy. A chest X-ray showed
      formation of a catheter loop inside the left brachiocephalic vein, probably due
      to hindrance by the dialysis catheter. This report describes the hurdles
      encountered, repeated cannulation attempts, and serial chest X-ray findings
      required to obtain acceptable placement of the catheter tip.

PMID- 27703639
TI  - Elaborate study design leads to improved conclusion.

PMID- 27703640
TI  - Evaluation of the Prevalence Rate and the Prognostic Effect of Human Papilloma
      Virus Infection in a Group of Patients With Oral Cavity Squamous Cell Carcinoma.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignancy of the
      oral cavity. A relationship between the human papilloma virus (HPV) infection and
      the prognosis of oral cavity SCC (OCSCC) has been discussed before. OBJECTIVES:
      We investigated the prevalence rate of HPV status in patients with OCSCC, and its
      effects on clinicopathological characteristics of tumors and patients' prognosis.
      PATIENTS AND METHODS: Sections of formalin-fixed, paraffin-embedded tissue blocks
      from 114 histopathologically confirmed OCSCC cases were investigated in this
      study. Polymerase chain reaction (PCR) was applied to evaluate the HPV status in
      the samples. RESULTS: Fifteen (13.16%) cases were identified as HPV positive. The
      detected viral subtypes in this study were the subtypes 6 and 11. The stage and
      especially lymph node stage was significantly higher in the HPV positive group
      compared to the HPV negative group (P = 0.04). Disease free survival (DFS) was
      remarkably lower in the HPV positive group compared to the HPV negative group
      (13.9 vs. 49.9 months, P = 0.02). Overall survival (OS) was also significantly
      inferior in the HPV positive group (15.7 vs. 49.6 months, P = 0.01). In the
      current study, no significant differences were observed between two groups in
      relation to the variables of age, gender, tumors site, tumor size, tumor grading
      and also the recurrence rate. CONCLUSIONS: The observed higher mortality rate
      among the HPV positive group indicates the poorer prognosis of this group in
      comparison with the HPV negative patients. The incidence rate of HPV infection
      was low in the studied samples; however, interaction of subtypes 6 and 11 of HPV
      in poorer prognosis of the patients and a carcinogenic role of HPV in OCSCC
      cannot be ruled out.

PMID- 27703641
TI  - Iranian Nurses Perceptions of Cancer Patients Quality of Life.
AB  - BACKGROUND: Cancer is the third main cause of death in Iran only after
      cardiovascular diseases and accidents. OBJECTIVES: The main aim of this research
      study was to identify nurses' understanding of cancer patients' Quality of Life
      (QoL) in an Iranian context. PATIENTS AND METHODS: This descriptive correlational
      study was conducted in an educative referral oncology center affiliated to
      Isfahan University of Medical Sciences, Isfahan, Iran in 2013. 50 pairs of cancer
      patients and their nurses were conveniently recruited. The sample of nurses were
      selected based on consensus sampling which included more than 70 percent of
      eligible nurses in the hospital. Patients and nurses were requested to complete
      the Farsi version of the world health organization quality of life (WHOQoL-BREF)
      questionnaire, separately. QoL was measured across four dimensions including
      physical, psychological, social relationship and environmental. RESULTS: The QoL
      mean domain scores of patients were 10.06, 11.88, 12.76 and 11.96, respectively.
      The corresponding scores of nurses were 11.6, 11.23, 12.65 and 12.07. Pearson
      correlations between patients and nurses scores were 0.42, 0.5, 0.25 and 0.58
      which revealed a fair to moderate agreement between nurses' and patients' scores
      in different domains. Paired samples t-test values indicated that physical QoL
      mean domain scores of patients were significantly lower than the corresponding
      drawings of nurses [t (49) = -3.41, P < 0.001]. CONCLUSIONS: The main finding of
      this QoL study was that nurses generally have a moderate understanding of cancer
      patients' QoL. Therefore, in order to meet different physio-psycho-social needs
      of patients, nurses must enhance their understanding of patients' QoL
      particularly in more subjective and personal domains like social domain using a
      holistic approach.

PMID- 27703642
TI  - Immunohistochemistry Study of P53 and C-erbB-2 Expression in Trophoblastic Tissue
      and Their Predictive Values in Diagnosing Malignant Progression of Simple Molar
      Pregnancy.
AB  - BACKGROUND: Finding a tumor marker to predict the aggressive behavior of molar
      pregnancy in early stages has yet been a topic for studies. OBJECTIVES: In this
      survey we planned to study patients with molar pregnancy to 1) assess the p53 and
      c-erbB-2 expression in trophoblastic tissue, 2) to study the relationship between
      their expression intensity and progression of a molar pregnancy to gestational
      trophoblastic neoplasia, and 3) to determine a cut off value for the amount of
      p53 and c-erbB-2 expression which might correlate with aggressive behavior of
      molar pregnancy. PATIENTS AND METHODS: In a prospective cross sectional study by
      using a high accuracy technique EnVision Tm system for immunohistochemistry
      staining of molar pregnancy samples, we evaluated p53 and c-erbB-2 expression in
      cytotrophoblast and syncytiotrophoblast and the correlation of their expression
      with progression of molar pregnancy to gestational trophoblastic neoplasia (GTN).
      Normal prostatic tissue and Breast cancer tissue were used as positive controls.
      RESULTS: We studied 28 patients with simple molar pregnancy (SMP) and 30 with
      GTN. Cytotrophobalst had significantly higher expression of p53 and c-erbB-2 and
      syncytiotrophoblast had greater expression of p53 in GTN group as compared to SMP
      group. The cut off values for percentage of p53 positive immunostained
      cytotrophoblast and syncytiotrophoblast were 5.5% and 2.5%. In c-erbB-2 positive
      membranous stained cytotrophoblast the cut off was 12.5%. CONCLUSIONS: Our data
      suggests that over expression of p53 and c-erbB-2 is associated with malignant
      progression of molar pregnancy. We encountered that high expression of p53 and c
      erbB-2 in trophoblastic cells could predict gestational trophoblastic neoplasia
      during the early stages.

PMID- 27703643
TI  - Stevens-Johnson Syndrome Patient Received Combination Chemotherapy Gemcitabine,
      Cisplatin, and 5-FU for Biliary Tract Cancer.
AB  - Stevens-Johnson syndrome has been an acute, usually self-limiting disease of the
      skin and mucous membranes. This case report has presented an evidence of the
      development Stevens - Johnson syndrome associated with combination chemotherapy
      administration of 5FU, gemcitabin and cisplatin in a patient with biliary tract
      cancer. Our case was a 54-year-old woman patient, a case of biliary tract cancer
      who has developed more severe symptoms of Stevens-Johnson syndrome. Diagnosis has
      confirmed by skin biopsy of an affected area .The patient has improved with
      supportive care, and during 25 day occurred recovery. Although Stevens-Johnson
      syndrome has been a rare toxicity, physicians should pay a special attention to
      the monitoring of biliary tract cancer patients on combination chemotherapy with
      5FU, cisplatin and gemcitabin.

PMID- 27703644
TI  - Rhabdomyosarcoma of Cervix: A Case Report.
AB  - INTRODUCTION: Rhabdomyosarcoma has known as a highly malignant soft tissue
      sarcoma. It has been the most common soft tissue sarcoma in childhood, accounting
      for about 3 to 4 % of all cases of childhood cancer. Rhabdomyosarcoma was rare in
      adults, accounting for 3% of all soft-tissue sarcomas. embryonal rhabdomyosarcoma
      of female genital tract including uterine cervix in an adult was rare. CASE
      PRESENTATION: This study has reported a 33-year-old woman presented with abnormal
      vaginal discharge. Gynecologic examination revealed a cervical mass with grape-
      like feature protruding into vagina with posterior- superior vaginal wall
      involvement. Biopsy has performed and pathologic examination was consistent with
      embryonal botryoid type rhabdomyosarcoma. She has undergone the staging work up
      measurements including thoracic computed tomography (CT) scan, abdominopelvic
      magnetic resonance imaging (MRI), bone scan and bone marrow examination. In
      exception of abdominopelvic MRI, with 2 suspicious pelvic lymph nodes in addition
      of cervical mass, all others were normal. Radical hysterectomy with lymph node
      debulking and ovarian preservation has performed. Final results have shown
      embryonal botryoid type rhabdomyosarcoma of cervix. ovaries, endometrium,
      parametrium, and follopian tubes were unremarkable. Pelvic lymph nodes pathology
      and intraabdominal fluid cytology were negative for malignancy. Lymphovascular
      invasion was identified. She has advised for adjuvant chemotherapy. CONCLUSIONS:
      This case has reminded that embryonal rhabdomyosarcoma could occur in uncommon
      site and older female. Longer follow up of these cases has required due to lack
      of survival data for embryonal rhabdomyosarcoma of this site and age group.

PMID- 27703645
TI  - The Correlation of Plasma 25-Hydroxyvitamin D Deficiency With Risk of Breast
      Neoplasms: A Systematic Review.
AB  - CONTEXT: Breast cancer has been considered as one of the most common types of
      cancer among the women worldwide, and patients with breast neoplasms have been
      reported with high prevalence of low serum 25-hydroxyvitamin D levels.
      OBJECTIVES: Our aim was to evaluate the correlation of plasma 25-hydroxyvitamin D
      deficiency with breast neoplasms risk among women. DATA SOURCES: PubMed database
      was searched with MeSH (medical subject headings) keywords "vitamin D AND breast
      neoplasms" which was restricted by original articles written only in English and
      published from January 1, 2014. STUDY SELECTION: To find the articles that met
      eligibility criteria, titles and abstracts were examined. DATA EXTRACTION: This
      systematic review was conducted according to PRISMA (preferred reporting items
      for systematic reviews and meta-analyses) statement. Critical appraising of
      evidence was performed, using the study quality assessment tools of national
      institutes of health, national heart, lung and blood institute (NHLBI). RESULTS:
      Overall, 76 potential articles were identified and after screening, 13 articles
      met eligible criteria for inclusion. Definition of low vitamin D levels varied
      greatly among studies, making comparisons difficult, but most of them have
      defined deficiency as 25(OH)D < 20 ng/mL. Evidence was mainly of fair quality.
      CONCLUSIONS: This study has provided evidence that vitamin D deficiency has been
      very prevalent in patients with breast neoplasms, more than comparable matched
      control population, and risk of breast cancer has increased with low vitamin D
      levels, suggesting the need for high quality studies that assessed the health
      consequences attributable to vitamin D deficiency employing standard definitions.

PMID- 27703646
TI  - Adenosine Deaminase Activity in Chronic Lymphocytic Leukemia and Healthy
      Subjects.
AB  - BACKGROUND: B cell chronic lymphocytic leukemia is one of the most frequent
      hematologic malignancies in the world. Cellular surface CD markers and serum Beta
      2-microglobulin may be used as a prognostic tool in CLL patients. OBJECTIVES: In
      the present study we introduce serum adenosine deaminase as a diagnostic marker
      in CLL. MATERIALS AND METHODS: Blood samples were collected from B-CLL and
      healthy subjects. White blood cell, red blood cell and platelet count and blood
      Erythrocyte sedimentation rate was recorded and serum Beta-2-microglobulin,
      Lactate dehydrogenase and total ADA enzyme activity were determined. RESULTS:
      Serum ADA activity was significantly higher in patients group than that of
      controls. ADA had a significant and direct correlation with B2M, WBC, LDH and
      ESR. However, there was not any relation between ADA and the stages of disease.
      Diagnostic cut-off, sensitivity and specificity of the serum ADA test were 27.97
      U/L, 91% and 94%, respectively. CONCLUSIONS: A higher ADA activity in patients
      group and its correlation with CLL markers were seen in our study. High
      diagnostic value of serum ADA in our study suggests that it might be considered
      as a useful screening tool among the other markers in CLL.

PMID- 27703647
TI  - The Prognostic Value of Age, Sex, and Subsite in Cutaneous Head and Neck
      Melanoma: A Clinical Review of Recent Literature.
AB  - CONTEXT: Cutaneous head and neck melanoma is a challenging disease owing to its
      aggressive nature and often times advanced stage at presentation. Age, sex, and
      subsite are three prognostic indicators which can be determined prior to
      treatment or testing, and can allow the practitioner to counsel the patient
      before initiating therapy. EVIDENCE ACQUISITION: A PubMed search was conducted
      utilizing various terms relating to the subject matter. Articles over the past 25
      years were analyzed and appropriately selected for review. RESULTS: It appears
      that patients older than 65 have a decreased overall 5 year survival compared to
      their younger counterparts. Male patients have poorer prognosis compared to
      female patients as noted by the decreased overall survival, decreased disease
      specific survival, and shorter time to distant metastasis. Scalp subsite was most
      uniformly accepted as having the worst prognosis in the head and neck, and may
      even serve as an independent prognostic indicator. CONCLUSIONS: Advanced age,
      male sex, and scalp subsite all portend poor prognosis in patients with cutaneous
      head and neck melanoma.

PMID- 27703648
TI  - Lactobacilli Differentially Modulate mTOR and Wnt/ beta-Catenin Pathways in
      Different Cancer Cell Lines.
AB  - BACKGROUND: Lactobacilli are a group of beneficial bacteria whose anti cancer
      effects have been evaluated in different cancer cell lines as well as animal
      models and human subjects. Such anti cancer effects can be exerted via different
      mechanisms such as modulation of immune response as well as inhibition of
      pathogens colonization. In addition, lactobacilli have direct cytotoxic effects
      against cancer cells which may be exerted through modulation of expression cancer
      related pathways. OBJECTIVES: The aim of this study is to find the mechanism of
      anti cancer effects of two lactobacilli strains, Lactobacillus. crispatus (LC)
      and Lactobacillus. rhamnosus (LR). MATERIALS AND METHODS: We analyzed expression
      of some mTOR and Wnt/ beta-catenin pathways genes in three cancer cell lines
      (HeLa, MDA-MB-231 and HT-29) following treatment with LC and LR culture
      supernatants. RESULTS: Of note, the expression of CCND1 as a marker of cell
      proliferation, survival, and angiogenesis, has been decreased following LR
      treatment in all cell lines. In addition, the expression of SFRP2, an antagonist
      of Wnt pathway, has been increased in HT-29 following LR treatment and in HeLa
      cells following LR and LC treatments. Furthermore, we have demonstrated the
      downregulation of S6K1 expression, a marker of poor prognosis, following LR
      treatment in HT-29 and following LR and LC treatments in MDA-MB-231 cell line.
      CONCLUSIONS: Consequently, lactobacilli can modulate expression of mTOR and Wnt/
      beta-catenin pathways genes in cancer cell lines in a strain specific as well as
      cell type specific manner.

PMID- 27703649
TI  - CT Simulation to Evaluate of Pelvic Lymph Node Coverage in Conventional
      Radiotherapy Fields Based on Bone and Vessels Landmarks in Prostate Cancer
      Patients.
AB  - BACKGROUND: Radiotherapy is the gold standard for treatment of prostrate cancer
      as it can cover an adequate area of tissues at risk for metastasis. OBJECTIVES:
      We evaluated the Pelvic lymph node coverage of conventional radiotherapy fields
      based on bone and vessels landmarks using computed tomography (CT) simulation in
      patients with prostate cancer referred to Shohada-e-Tajrish hospital. PATIENTS
      AND METHODS: In this cross sectional study, 40 patients with prostate cancer at
      the Stage T1c to T3b were studied. Pelvic lymph nodes were contoured by using
      pelvic vessels as surrogate markers. The distances were measured at different
      points of anterior-posterior (AP) and lateral fields and distances > 5 mm or more
      between the contoured nodes and the field borders. RESULTS: Mean and standard
      deviation of the aortic bifurcation from the superior border was 4.73 +/- 1.16
      cm, the distance of common iliac bifurcation from the superior border was 1.11 +/
      1.25 cm, the mean (SD) distance of right external iliac from the lateral border
      of AP field was 2.06 +/- 0.48 cm and for left external iliac artery was 1.90 +/-
      0.56 cm. The distance of the external iliac artery from the anterior border of
      the lateral field was 2.30 +/- 0.74 cm. The distance of the external iliac artery
      from pelvic rim was 0.59 +/- 0.59 cm, distance of bifurcation of iliac from
      sacroiliac joint was 0.82 +/- 1.01 cm, the size of the pelvic rim was 12.30 +/-
      0.64 cm, sacral width was 8.29 +/- 1.01 cm, anterior promontory symphysis
      distance was 12.02 +/- 0.92 cm and posterior promontory symphysis distance was
      10.98 +/- 0.73 cm. CONCLUSIONS: We observed that conventional radiotherapy using
      CT simulation based on bone and vessels landmarks provided adequate coverage of
      pelvic lymph nodes in our patients with prostate cancer.

PMID- 27703651
TI  - Cancer Screening, Effective or Harmful?

PMID- 27703650
TI  - Genetic Variations in Leptin and Leptin Receptor and Susceptibility to Colorectal
      Cancer and Obesity.
AB  - BACKGROUND: Colorectal cancer (CRC) is the second most commonly diagnosed cancer
      and the fourth leading cause of cancer-related mortality around the world.
      OBJECTIVES: With regard to the role of obesity in colorectal cancer (CRC) and the
      role of leptin in obesity, we investigated whether leptin (LEP) and leptin
      receptor (LEPR) gene variants are associated with CRC risk. PATIENTS AND METHODS:
      We evaluated LEP (rs7799039) and LEPR (rs1137101) gene variants by using PCR-RFLP
      method in 261 cases with CRC and 339 controls. RESULTS: No significant difference
      was found for rs7799039 and rs1137101gene variants between the cases with CRC and
      controls. However, the LEPR rs1137101 "GG" genotype compared with "AA" genotype
      and "AA + AG" genotype was associated with increased risks for obesity, and the
      differences remained significant after adjustment for confounding factors
      including age, sex, smoking status, and NSAID use (P = 0.015; OR = 2.42, 95%CI =
      1.19 - 4.93 and P = 0.016; OR = 2.28, 95%CI = 1.17 - 4.48, respectively). In
      addition, the LEPR "G" allele compared with the "A" allele was associated with an
      increased risk for obesity (P = 0.024; OR = 1.44, 95%CI = 1.05 - 1.98).
      CONCLUSIONS: Consistent with most previous studies, our findings found no
      association between LEP (rs7799039) and LEPR (rs1137101) gene variants and CRC
      risk. However, the LEPR rs1137101 "GG" genotype compared with the "AA" genotype
      and "AA+AG" genotype was associated with a 2.42-fold and a 2.28-fold increased
      risk for obesity, respectively.

PMID- 27703652
TI  - Detection of a Rare Complication of Congenital Cystic Adenomatoid Malformation in
      a Recipient Twin with Twin-Twin Transfusion Syndrome Using Prenatal Magnetic
      Resonance Imaging.

PMID- 27703653
TI  - An Intracranial Gliosis Mimicking Neoplasm: A Dilemma.
AB  - Intracranial gliosis has no typical clinical signals or imaging characteristics.
      Therefore, it can be easily misdiagnosed as neoplasm. Hereby, we report a unique
      case of gliosis that grew outward from the surface of the brain. MRI depicted its
      signal and enhancement pattern similar to the cerebral gray matter. The diagnosis
      was confirmed by pathology and immunohistochemistry. Although it was difficult to
      reach a diagnosis, correlating its origin, growing pattern and MR features and
      knowing that gliosis can present this way may help in differentiating it from
      other diseases.

PMID- 27703654
TI  - Diagnostic Accuracy of Dynamic Contrast Enhanced Magnetic Resonance Imaging in
      Characterizing Lung Masses.
AB  - BACKGROUND: Imaging plays a critical role not only in the detection, but also in
      the characterization of lung masses as benign or malignant. OBJECTIVES: To
      determine the diagnostic accuracy of dynamic magnetic resonance imaging (MRI) in
      the differential diagnosis of benign and malignant lung masses. PATIENTS AND
      METHODS: Ninety-four masses were included in this prospective study. Five dynamic
      series of T1-weighted spoiled gradient echo (FFE) images were obtained, followed
      by a T1-weighted FFE sequence in the late phase (5th minutes). Contrast
      enhancement patterns in the early (25th second) and late (5th minute) phase
      images were evaluated. For the quantitative evaluation, signal intensity (SI)
      time curves were obtained and the maximum relative enhancement, wash-in rate, and
      time-to-peak enhancement of masses in both groups were calculated. RESULTS: The
      early phase contrast enhancement patterns were homogeneous in 78.2% of the benign
      masses, while heterogeneous in 74.4% of the malignant tumors. On the late phase
      images, 70.8% of the benign masses showed homogeneous enhancement, while most of
      the malignant masses showed heterogeneous enhancement (82.4%). During the first
      pass, the maximum relative enhancement and wash-in rate values of malignant
      masses were significantly higher than those of the benign masses (P = 0.03 and
      0.04, respectively). The cutoff value at 15% yielded a sensitivity of 85.4%,
      specificity of 61.2%, and positive predictive value of 68.7% for the maximum
      relative enhancement. CONCLUSION: Contrast enhancement patterns and SI-time curve
      analysis of MRI are helpful in the differential diagnosis of benign and malignant
      lung masses.

PMID- 27703655
TI  - Brain Tissue Classification Based on Diffusion Tensor Imaging: A Comparative
      Study Between Some Clustering Algorithms and Their Effect on Different Diffusion
      Tensor Imaging Scalar Indices.
AB  - BACKGROUND: Brain segmentation from diffusion tensor imaging (DTI) into white
      matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) with acceptable
      results is subjected to many factors. OBJECTIVES: The most important issue in
      brain segmentation from DTI images is the selection of suitable scalar indices
      that best describe the required tissue in the images. Specifying suitable
      clustering method and suitable number of clusters of the selected method are
      other factors which affects the segmentation process significantly. MATERIALS AND
      METHODS: The segmentation process is evaluated using four different clustering
      methods with different number of clusters where some DTI scalar indices for 10
      human brains are processed. RESULTS: The aim was to produce results with less
      segmentation error and a lower computational cost while attempting to minimizing
      boundary overlapping and minimizing the effect of artifacts due to macroscale
      scanning. CONCLUSION: The volume ratios of the best produced outputs with respect
      to the total brain size are 16.7% +/- 3.53% for CSF, 35.05% +/- 1.13% for WM, and
      48.2% +/- 2.88% for GM.

PMID- 27703656
TI  - Diagnostic Value of Dual-Source Computerized Tomography Combined with Perfusion
      Imaging for Peripheral Pulmonary Embolism.
AB  - BACKGROUND: Pulmonary embolism has become the third most common cardiovascular
      disease, which can seriously harm human health. OBJECTIVES: To investigate the
      diagnostic value of dual-source computerized tomography (CT) and perfusion
      imaging for peripheral pulmonary embolism. PATIENTS AND METHODS: Thirty-two
      patients with suspected pulmonary embolism underwent dual-source CT exams. To
      compare the ability of pulmonary embolism detection software (PED) with CT
      pulmonary angiography (CTPA) in determining the presence, numbers, and locations
      of pulmonary emboli, the subsequent images were reviewed by two radiologists
      using both imaging modalities. Also, the diagnostic consistency between PED and
      CTPA images and dual-energy pulmonary perfusion imaging (DEPI) for segmental
      pulmonary embolism was compared. RESULTS: CTPA images revealed 50 (7.81%)
      segmental and 56 (4.38%) sub-segmental pulmonary embolisms, while the PED images
      showed 68 (10.63%) segmental and 94 (7.34%) sub-segmental pulmonary embolisms.
      Thus, the detection rate on PED images for peripheral pulmonary embolism was
      significantly higher than that of the CTPA images (P < 0.05). There was good
      consistency for diagnosing segmental pulmonary embolism between PED and CTPA and
      DEPI (kappa = 0.85). The sensitivity and specificity of DEPI images for the
      diagnosis of pulmonary embolism were 91.7% and 97.5%, respectively. CONCLUSION:
      PED software of dual-source CT combined with perfusion imaging can significantly
      improve the detection rate of peripheral pulmonary embolism.

PMID- 27703658
TI  - Diagnostic Performance on Low Dose Computed Tomography For Acute Appendicitis
      Among Attending and Resident Radiologists.
AB  - BACKGROUND: Low-dose computed tomography (LDCT) techniques can reduce exposure to
      radiation. Several previous studies have shown that radiation dose reduction in
      LDCT does not decrease the diagnostic performance for appendicitis among
      attending radiologists. But, the LDCT diagnostic performance for acute
      appendicitis in radiology residents with variable training levels has not been
      well discussed. OBJECTIVES: To compare inter-observer and intra-observer
      differences of diagnostic performance on non-enhanced LDCT (NE-LDCT) and contrast
      enhanced standard dose CT (CE-SDCT) for acute appendicitis among attending and
      resident radiologists. PATIENTS AND METHODS: This retrospective study included
      101 patients with suspected acute appendicitis who underwent NE-LDCT and CE-SDCT.
      The CT examinations were interpreted and recorded on a five-point scale
      independently by three attending radiologists and three residents with 4, 1 and 1
      years of training. Diagnostic performance for acute appendicitis of all readers
      on both examinations was represented by area under receiver operating
      characteristic (ROC) curves. Inter-observer and intra-observer AUC values were
      compared using Jackknife FROC software on both modalities. The diagnostic
      accuracy of each reader on NE-LDCT was compared with body mass index (BMI)
      subgroups and noise using independent T test. RESULTS: Diagnostic performances
      for acute appendicitis were not statistically different for attending
      radiologists at both examinations. Better performance was noted on the CE-SDCT
      with a borderline significant difference (P = 0.05) for senior radiology
      resident. No statistical difference of AUC values was observed between attending
      radiologists and fourth year resident on both examinations. Statistically
      significant differences of AUC values were observed between attending
      radiologists and first year residents (P = 0.001 ~ 0.018) on NE-LDCT. Diagnostic
      accuracies of acute appendicitis on NE-LDCT for each reader were not
      significantly related to BMI or noise. CONCLUSION: Attending radiologists could
      diagnose acute appendicitis accurately on NE-LDCT. Performance of senior
      residents on NE-LDCT is better than junior residents and comparable to attending
      radiologists.

PMID- 27703659
TI  - Imaging Features of Breast Dermatofibrosarcoma Protuberans in Various Modalities
      Including FDG-PET CT.
AB  - Dermatofibrosarcoma protuberans is an uncommon malignant mesenchymal tumor of the
      dermis, which most commonly appears on the body and extremities. A preoperative
      diagnosis of dermatofibrosarcoma protuberans is extremely difficult, because it
      is a very rare entity and its appearance is often similar to that of benign
      breast lesion. Here, we presented a case of breast dermatofibrosarcoma
      protuberans with associated radiological mammography, ultrasound, magnetic
      resonance imaging and fludeoxyglucose-positron emission tomography computerized
      tomography (FDG-PET CT) features. To our knowledge, our case is the first report
      of PET-CT findings of breast dermatofibrosarcoma protuberans. Furthermore, we
      reviewed characteristic radiologic features of this rare entity, which are
      helpful for differentiating it from other primary benign breast lesions.

PMID- 27703657
TI  - Lower Extremity Arterial Calcification as a Predictor of Coronary Atherosclerosis
      in Patients with Peripheral Arterial Disease.
AB  - BACKGROUND: Until now, there has been no study on the relationship between the
      calcification of the lower extremity arteries and significant coronary arterial
      disease (CAD). OBJECTIVES: To evaluate whether lower extremity calcium scores
      (LECS) are associated with CAD and whether this can predict multivessel-CAD in
      patients with peripheral arterial disease (PAD). PATIENTS AND METHODS: We
      retrospectively enrolled 103 PAD patients without cardiac symptoms or known CAD.
      All patients underwent cardiac computed tomography (CT) and lower extremity CT
      within 1 month and were categorized as nonsignificant CAD, single-CAD, or
      multivessel-CAD. The coronary calcium scores (CCS) were quantitatively measured
      according to the Agatston method and LECS were semi-quantitatively measured
      according to the presence of lower extremity calcification in the segment. The
      extent of CAD was evaluated according to the presence of >= 50% luminal diameter
      stenosis in the segment of CAD. RESULTS: LECS in multivessel-CAD were
      significantly higher than those in nonsignificant CAD (10.0 +/- 5.8 versus 4.0 +/
      3.1, P < 0.001). LECS significantly correlated with CCS (r = 0.831, P < 0.001)
      and the extent of CAD (r = 0.631, P < 0.001). Multivariate regression analysis
      demonstrated LECS and log-transformed CCS were independent predictors for
      multivessel-CAD. In receiver operating characteristic curve analysis, the
      diagnostic performance of LECS was 0.807 (95% confidence interval = 0.724-0.891,
      P < 0.001) for predicting multivessel-CAD. CONCLUSION: Peripheral arterial
      calcification is significantly correlated with CAD extent in patients with PAD.
      Peripheral arterial calcification can be a useful marker for predicting
      multivessel-CAD.

PMID- 27703660
TI  - Dual-Source Computed Tomography Evaluation of Children with Congenital Pulmonary
      Valve Stenosis.
AB  - BACKGROUND: Despite dual-source computed tomography (DSCT) technology has been
      performed well on adults or infants with heart disease, specific knowledge about
      children with congenital pulmonary valve stenosis (PS) remained to be
      established. OBJECTIVES: This original research aimed to establish a professional
      approach of DSCT performing technology on children and to assess the image
      quality performed by DSCT to establish a diagnostic evaluation for children with
      PS. PATIENTS AND METHODS: Ninety-eight children with congenital PS referred to
      affiliated hospital of Jining medical college were recruited from October 2013 to
      March 2015. Participants were divided into four groups according to different
      ages (0 - 1, 1 - 3, 3 - 7, 7 - 14), or three groups according to different heart
      rates (< 90, 90 - 110, > 110). Image quality of pulmonary valves was assessed
      based on a four-point grading scale (1 - 4 points). Those cases achieving a score
      of >= 3 points were selected for further investigation, which played a critical
      role in our analysis. Correlation analysis was used to identify the effects of
      age and heart rate on image quality. Additionally, the results evaluated by DSCT
      were compared with those evaluated from the operation, further confirming the
      accuracy of DSCT. RESULTS: Seventy-two cases (73.4%) achieved a score of >= 3
      points based on pulmonary valve imaging, which were available for further
      diagnosis. There was a statistically significant difference (P < 0.05) between
      the four groups except 0 - 1 group and 1 - 3 group, 3 - 7 group and 7 - 14 group,
      and the image quality of elder group was higher than younger group. Image score
      was gradually decreased with increased heart rate (F = 19.05, P < 0.01). Heart
      rate was negatively correlated with pulmonary valve scores (r = -0.391, P <
      0.001), while there was no correlation between age and scores (r = 0.185, P =
      0.070). The number, shape, commissure, and opening status of pulmonary valves
      evaluated by DSCT were the same as the results of operation. CONCLUSION: Heart
      rate serves a pivotal role in imaging quality of DSCT. DSCT provides a functional
      evaluation of children with congenital PS and consequently contributes to a
      theoretical basis for corresponding treatment protocols.

PMID- 27703661
TI  - Quantitative Evaluation of the Fetal Cerebellar Vermis Using the Median View on
      Two-Dimensional Ultrasound.
AB  - BACKGROUND: Evaluation of the cerebellum and vermis is one of the integral parts
      of the fetal cranial anomaly screening. OBJECTIVES: The aim of this study was to
      create a nomogram for fetal vermis measurements between 17 and 30 gestational
      weeks. PATIENTS AND METHODS: This prospective study was conducted on 171
      volunteer pregnant women between March 2013 and December 2014. Measurements of
      the fetal cerebellar vermis diameters in the sagittal plane were performed by two
      dimensional transabdominal ultrasonography. RESULTS: Optimal median planes were
      obtained in 117 of the cases. Vermian diameters as a function of gestational age
      were expressed by regression equations and the correlation coefficients were
      found to be highly statistically significant (P < 0.001). The normal mean (+/-
      standard deviation) for each gestational week was also defined. CONCLUSION: This
      study presents the normal range of the two-dimensional fetal vermian measurements
      between 17 and 30 gestational weeks. In the absence of a three-dimensional
      ultrasonography, two-dimensional ultrasonography could also be used confidently
      with more time and effort.

PMID- 27703662
TI  - In Vivo Evaluation of the Biomechanical Properties of Optic Nerve and
      Peripapillary Structures by Ultrasonic Shear Wave Elastography in Glaucoma.
AB  - BACKGROUND: Primary open-angle glaucoma is a multifactorial serious disease
      characterized by progressive retinal ganglion cell death and loss of visual
      field. OBJECTIVES: The purposes of this study were to investigate shear wave
      elastography (SWE) use in the evaluation of the optic nerve (ON) and
      peripapillary structures, and to compare the findings between glaucomatous and
      control eyes. PATIENTS AND METHODS: A case-controlled study, including 21
      patients with primary open-angle glaucoma and 21 age-matched control subjects,
      was carried out. All of the participants had comprehensive ophthalmological exams
      that included corneal biomechanical measurements with ocular response analyzer.
      In vivo evaluation of the biomechanical properties of the ON and peripapillary
      structures were performed with SWE in all participants. The Kolmogorov-Smirnov
      test was used to analyze the normal distribution of data. Differences of
      parameters in ophthalmologic data and stiffness values of patients with and
      without glaucoma were evaluated using the Mann-Whitney U test. RESULTS: There
      were no statistically significant differences between the glaucoma and control
      groups in terms of age (P > 0.05) and gender (P > 0.05). Corneal hysteresis was
      lower in the glaucoma group (P < 0.05). Corneal compensated intraocular pressure
      and Goldmann correlated intraocular pressure were higher in the glaucoma group (P
      < 0.0001 for both). The mean stiffness of the ON and peripapillary structures
      were significantly higher in glaucoma patients for each measured region (P <
      0.05). CONCLUSION: The study evaluated the biomechanical properties of the ON and
      peripapillary structures in vivo with SWE in glaucoma. We observed stiffer ON and
      peripapillary tissue in glaucomatous eyes, indicating that SWE claims new
      perspectives in the evaluation of ON and peripapillary structures in glaucoma
      disease.

PMID- 27703665
TI  - IncucyteDRC: An R package for the dose response analysis of live cell imaging
      data.
AB  - We present IncucyteDRC, an R package for the analysis of data from live cell
      imaging cell proliferation experiments carried out on the Essen Biosciences
      IncuCyte ZOOM instrument. The package provides a simple workflow for summarising
      data into a form that can be used to calculate dose response curves and EC50
      values for small molecule inhibitors. Data from different cell lines, or cell
      lines grown under different conditions, can be normalised as to their doubling
      time. A simple graphical web interface, implemented using shiny, is provided for
      the benefit of non-R users. The software is potentially useful to any research
      group studying the impact of small molecule inhibitors on cell proliferation
      using the IncuCyte ZOOM.

PMID- 27703663
TI  - How leukocytes trigger opening and sealing of gaps in the endothelial barrier.
AB  - The entry of leukocytes into tissues requires well-coordinated interactions
      between the immune cells and endothelial cells which form the inner lining of
      blood vessels. The molecular basis for recognition, capture, and adhesion of
      leukocytes to the endothelial apical surface is well studied. This review will
      focus on recent advances in our understanding of events following the firm
      interaction of leukocytes with the inner surface of the blood vessel wall. We
      will discuss how leukocytes initiate the transmigration (diapedesis) process,
      trigger the opening of gaps in the endothelial barrier, and eventually move
      through this boundary.

PMID- 27703666
TI  - ddpcr: an R package and web application for analysis of droplet digital PCR data.
AB  - Droplet digital polymerase chain reaction (ddPCR) is a novel platform for exact
      quantification of DNA which holds great promise in clinical diagnostics. It is
      increasingly popular due to its digital nature, which provides more accurate
      quantification and higher sensitivity than traditional real-time PCR. However,
      clinical adoption has been slowed in part by the lack of software tools available
      for analyzing ddPCR data. Here, we present ddpcr - a new R package for ddPCR
      visualization and analysis. In addition, ddpcr includes a web application
      (powered by the Shiny R package) that allows users to analyze ddPCR data using an
      interactive graphical interface.

PMID- 27703664
TI  - Recent advances in T-cell engineering for use in immunotherapy.
AB  - Adoptive T-cell therapies have shown exceptional promise in the treatment of
      cancer, especially B-cell malignancies. Two distinct strategies have been used to
      redirect the activity of ex vivo engineered T cells. In one case, the well-known
      ability of the T-cell receptor (TCR) to recognize a specific peptide bound to a
      major histocompatibility complex molecule has been exploited by introducing a TCR
      against a cancer-associated peptide/human leukocyte antigen complex. In the other
      strategy, synthetic constructs called chimeric antigen receptors (CARs) that
      contain antibody variable domains (single-chain fragments variable) and signaling
      domains have been introduced into T cells. Whereas many reviews have described
      these two approaches, this review focuses on a few recent advances of significant
      interest. The early success of CARs has been followed by questions about optimal
      configurations of these synthetic constructs, especially for efficacy against
      solid tumors. Among the many features that are important, the dimensions and
      stoichiometries of CAR/antigen complexes at the synapse have recently begun to be
      appreciated. In TCR-mediated approaches, recent evidence that mutated peptides
      (neoantigens) serve as targets for endogenous T-cell responses suggests that
      these neoantigens may also provide new opportunities for adoptive T-cell
      therapies with TCRs.

PMID- 27703667
TI  - Rapid and high throughput molecular identification of diverse mosquito species by
      high resolution melting analysis.
AB  - Mosquitoes are a diverse group of invertebrates, with members that are among the
      most important vectors of diseases. The correct identification of mosquitoes is
      paramount to the control of the diseases that they transmit. However,
      morphological techniques depend on the quality of the specimen and often
      unavailable taxonomic expertise, which may still not be able to distinguish
      mosquitoes among species complexes (sibling and cryptic species). High resolution
      melting (HRM) analyses, a closed-tube, post-polymerase chain reaction (PCR)
      method used to identify variations in nucleic acid sequences, has been used to
      differentiate species within the Anopheles gambiae and Culex pipiens complexes.
      We validated the use of PCR-HRM analyses to differentiate species within
      Anopheles and within each of six genera of culicine mosquitoes, comparing primers
      targeting cytochrome b ( cyt b), NADH dehydrogenase subunit 1 (ND1), intergenic
      spacer region (IGS) and cytochrome c oxidase subunit 1 ( COI) gene regions. HRM
      analyses of amplicons from all the six primer pairs successfully differentiated
      two or more mosquito species within one or more genera ( Aedes ( Ae. vittatus
      from Ae. metallicus), Culex ( Cx. tenagius from Cx. antennatus, Cx. neavei from
      Cx. duttoni, cryptic Cx. pipiens species), Anopheles ( An. gambiae s.s. from An.
      arabiensis) and Mansonia ( Ma. africana from Ma. uniformis)) based on their HRM
      profiles. However, PCR-HRM could not distinguish between species within Aedeomyia
      ( Ad. africana and Ad. furfurea), Mimomyia ( Mi. hispida and Mi. splendens) and
      Coquillettidia ( Cq. aurites, Cq. chrysosoma, Cq. fuscopennata, Cq. metallica,
      Cq. microannulatus, Cq. pseudoconopas and Cq. versicolor) genera using any of the
      primers. The IGS and COI barcode region primers gave the best and most definitive
      separation of mosquito species among anopheline and culicine mosquito genera,
      respectively, while the other markers may serve to confirm identifications of
      closely related sub-species. This approach can be employed for rapid
      identification of mosquitoes.

PMID- 27703668
TI  - Protein domain architectures provide a fast, efficient and scalable alternative
      to sequence-based methods for comparative functional genomics.
AB  - A functional comparative genome analysis is essential to understand the
      mechanisms underlying bacterial evolution and adaptation. Detection of functional
      orthologs using standard global sequence similarity methods faces several
      problems; the need for defining arbitrary acceptance thresholds for similarity
      and alignment length, lateral gene acquisition and the high computational cost
      for finding bi-directional best matches at a large scale. We investigated the use
      of protein domain architectures for large scale functional comparative analysis
      as an alternative method. The performance of both approaches was assessed through
      functional comparison of 446 bacterial genomes sampled at different taxonomic
      levels. We show that protein domain architectures provide a fast and efficient
      alternative to methods based on sequence similarity to identify groups of
      functionally equivalent proteins within and across taxonomic bounderies. As the
      computational cost scales linearly, and not quadratically with the number of
      genomes, it is suitable for large scale comparative analysis. Running both
      methods in parallel pinpoints potential functional adaptations that may add to
      bacterial fitness.

PMID- 27703669
TI  - Factors affecting stone free rate of primary percutaneous nephrolithotomy on
      staghorn calculi: a single center experience of 15 years.
AB  - Objectives: Percutaneous nephrolithotomy on staghorn calculi is challenging for
      urologists because it is difficult to remove all of the stones. The purpose of
      this study was to evaluate the associated factors of stone-free rate after
      primary percutaneous nephrolithotomy on staghorn calculi in a large series of
      patients at a single, tertiary referral, endourologic stone center. Methods: We
      collected data from medical record between January 2000 and December 2015. A
      total of 345 primary percutaneous nephrolithotomy procedures were performed for
      patients with staghorn calculi. This study included both and made no distinction
      between partial and complete staghorn calculi. Stone-free is defined as the
      absence of residual stones after undergoing percutaneous nephrolithotomy for the
      first time. Significant factors from univariate analysis that correlated with
      stone-free rate after primary percutaneous nephrolithotomy of staghorn stone were
      further analyzed using multivariate regression analysis. Results: The mean
      patient age was 52.23+/-10.38 years. The stone-free rate of percutaneous
      nephrolithotomy monotherapy was 62.6%. The mean operating time was 79.55+/-34.46
      minutes. The mean length of stay in hospital was 4.29+/-3.00 days. Using the chi
      square test, history of ipsilateral open renal stone surgery ( p = 0.01), stone
      burden ( p = < 0.001), and type of anesthesia ( p = 0.04) had a significant
      impact on the stone-free. From multivariate analysis, the history of ipsilateral
      open renal stone surgery [OR 0.48; 95% CI 0.28-0.81; p 0.01] and the stone burden
      [OR 0.28; 95% CI 0.18-0.45; p 0.00] were significant independent risk factors for
      stone-free.

PMID- 27703670
TI  - Opportunities and considerations for visualising neuroimaging data on very large
      displays.
AB  - Neuroimaging experiments can generate impressive volumes of data and many images
      of the results. This is particularly true of multi-modal imaging studies that use
      more than one imaging technique, or when imaging is combined with other
      assessments. A challenge for these studies is appropriate visualisation of
      results in order to drive insights and guide accurate interpretations. Next
      generation visualisation technology therefore has much to offer the neuroimaging
      community. One example is the Imperial College London Data Observatory; a high
      resolution (132 megapixel) arrangement of 64 monitors, arranged in a 313 degree
      arc, with a 6 metre diameter, powered by 32 rendering nodes. This system has the
      potential for high-resolution, large-scale display of disparate data types in a
      space designed to promote collaborative discussion by multiple researchers and/or
      clinicians. Opportunities for the use of the Data Observatory are discussed, with
      particular reference to applications in Multiple Sclerosis (MS) research and
      clinical practice. Technical issues and current work designed to optimise the use
      of the Data Observatory for neuroimaging are also discussed, as well as possible
      future research that could be enabled by the use of the system in combination
      with eye-tracking technology.

PMID- 27703671
TI  - Epidemiology, virulence factors and management of the pneumococcus.
AB  - Pneumococcal infections continue to cause significant morbidity and mortality in
      patients throughout the world. This microorganism remains the most common
      bacterial cause of community-acquired pneumonia and is associated with a
      considerable burden of disease and health-care costs in both developed and
      developing countries. Emerging antibiotic resistance has been a concern because
      of its potential negative impact on the outcome of patients who receive standard
      antibiotic therapy. However, there have been substantial changes in the
      epidemiology of this pathogen in recent years, not least of which has been due to
      the use of pneumococcal conjugate vaccines in children, with subsequent herd
      protection in unvaccinated adults and children. Furthermore, much recent research
      has led to a better understanding of the virulence factors of this pathogen and
      their role in the pathogenesis of severe pneumococcal disease, including the
      cardiac complications, as well as the potential role of adjunctive therapy in the
      management of severely ill cases. This review will describe recent advances in
      our understanding of the epidemiology, virulence factors, and management of
      pneumococcal community-acquired pneumonia.

PMID- 27703672
TI  - Ending the HIV/AIDS epidemic in low- and middle-income countries by 2030: is it
      possible?
AB  - The international community has committed to ending the epidemics of HIV/AIDS,
      tuberculosis, malaria, and neglected tropical infections by 2030, and this bold
      stance deserves universal support. In this paper, we discuss whether this
      ambitious goal is achievable for HIV/AIDS and what is needed to further
      accelerate progress. The joint United Nations Program on HIV/AIDS (UNAIDS) 90-90
      90 targets and the related strategy are built upon currently available health
      technologies that can diagnose HIV infection and suppress viral replication in
      all people with HIV. Nonetheless, there is much work to be done in ensuring
      equitable access to these HIV services for key populations and those who remain
      outside the rims of the traditional health services. Identifying a cure and a
      preventive vaccine would further help accelerate progress in ending the epidemic.
      Other disease control programmes could learn from the response to the HIV/AIDS
      epidemic.

PMID- 27703674
TI  - Correlation between secondary thrombosis in epileptic patients and serum levels
      of folate and vitamin B12.
AB  - Epilepsy is a chronic brain dysfunction syndrome and nervous system disease whose
      pathogenesis remains to be determined. The aim of the present study was to
      analyze the correlation between secondary thrombosis and the serum levels of
      folate and vitamin B12 in epileptic patients, as well as to determine whether the
      supplementation of folate and vitamin B12 was associated with a decreased
      incidence of thrombosis, and provide the basis for novel clinical treatment. A
      total of 37 patients, diagnosed as epileptic with secondary thrombosis between
      April 2012 and April 2014, were included in the treatment group. A total of 37
      epileptic patients without secondary thrombosis were included in the control
      group. The serum levels of homocysteine, folate and vitamin B12 in the two groups
      and in the epileptic patients with intracranial thrombosis or peripheral
      thrombosis were compared. According to the Guidance of Epilepsy, the patients in
      the two groups were administered antiepileptic drugs (AEDs) with the
      supplementation of folate tablet (0.4 mg/day) and vitamin B12 tablet (100
      ug/day). These indicators and the incidence of thrombosis in the two groups were
      compared after 1 year. The serum levels of homocysteine in the two groups were
      higher than normal, and the levels in the treatment group were significantly
      higher than those in the control group. The serum levels of folate and vitamin
      B12 in the treatment group were significantly higher than those in the control
      group and the difference was statistically significant (P<0.05). The Pearson
      correlation analysis revealed that the serum levels of folate and vitamin B12
      were not associated with the serum level of homocysteine (P>0.05). The logistic
      regression analysis revealed that the serum levels of folate and vitamin B12 were
      independent risk factors for epilepsy with secondary thrombosis [folate: odds
      ratio (OR)=0.635, P=0.038; vitamin B12: OR=0.418, P=0.042]. The differences in
      the serum levels of homocysteine, folate and vitamin B12 in the epileptic
      patients with intracranial thrombosis or peripheral thrombosis were not
      statistically significant (P>0.05). The serum levels of homocysteine in the two
      groups, were significantly decreased, while the levels of folate and vitamin B12
      were significantly increased. The differences in the serum levels of
      homocysteine, folate and vitamin B12 in the two groups were not statistically
      significant (P>0.05). The differences in the incidence of thrombosis in the two
      groups were not statistically significant (P>0.05). In conclusion, the serum
      levels of folate and vitamin B12 were independent of serum homocysteine, and were
      the dependent risk factors for primary epilepsy with secondary thrombosis. The
      supplementation of folate and vitamin B12 may be beneficial for the prevention of
      epilepsy with secondary thrombosis, making it valuable in application.

PMID- 27703675
TI  - Bowel movement frequency, oxidative stress and disease prevention.
AB  - The significance of diet for disease prevention has long been recognised. Dietary
      recommendations have therefore been integrated in health promotion messages.
      Gastrointestinal functioning is essential for the digestion of nutrients.
      Oxidative stress has been observed in patients with constipation, as well as in
      those with colorectal cancer, cardiovascular disease and other chronic illnesses
      associated with constipation. The coexistence of colorectal neoplasia and
      coronary artery disease has been incriminated for exposure to common risk factors
      associated with increased oxidative stress. It was recently demonstrated that
      bowel movement frequency is inversely associated with cardiovascular mortality.
      The aim of the present study was to review the relevant literature in light of
      these findings. It was concluded that suboptimal functioning of the large bowel
      may contribute to oxidative stress and, therefore, to increased mortality. Bowel
      movement frequency may represent a simple quantifiable indicator of adequate
      colonic function and it is dependent on diet, exercise and other lifestyle
      factors, but also on individual characteristics, including colonic microbiota.
      Future health promotion actions may improve the prevention of a number of
      diseases by advocating lifestyle personalisation for assuring optimal intestinal
      functioning.

PMID- 27703673
TI  - Plasticity of the Leishmania genome leading to gene copy number variations and
      drug resistance.
AB  - Leishmania has a plastic genome, and drug pressure can select for gene copy
      number variation (CNV). CNVs can apply either to whole chromosomes, leading to
      aneuploidy, or to specific genomic regions. For the latter, the amplification of
      chromosomal regions occurs at the level of homologous direct or inverted repeated
      sequences leading to extrachromosomal circular or linear amplified DNAs. This
      ability of Leishmania to respond to drug pressure by CNVs has led to the
      development of genomic screens such as Cos-Seq, which has the potential of
      expediting the discovery of drug targets for novel promising drug candidates.

PMID- 27703676
TI  - Associations and prognostic significance of p27Kip1, Jab1 and Skp2 in non-Hodgkin
      lymphoma.
AB  - Non-Hodgkin lymphoma (NHL) is a primary tumor arising in lymph nodes and lymphoid
      tissue. The incidence of NHL is increasing at an annual rate of 3%. The human Jun
      activation domain-binding protein 1/COP9 signalosome subunit 5 (Jab1/CSN5) is a
      negative regulator of the cell cycle inhibitor p27Kip1 and abnormal expression of
      Jab1 is correlated with reduced p27 expression and associated with advanced tumor
      stage and poor prognosis in several human cancers. F-box protein S-phase kinase
      interacting protein-2 (Skp2), the substrate recognition subunit of the Skp1-Cul1
      F-box protein ubiquitin protein ligase complex, is required for the
      ubiquitination and consequent degradation of p27. The Skp2 protein is
      overexpressed in several human cancers and is associated with the degree of
      differentiation and the prognosis. The aim of the present study was to
      investigate the expression status of p27Kip1, Jab1 and Skp2 by
      immunohistochemistry, and assess their prognostic significance in patients with
      NHL. Immunohistochemical analysis revealed an inverse association between Jab1
      and p27 in NHL tissue samples. Kaplan-Meier analysis demonstrated that Jab1
      overexpression, Skp2 overexpression and low p27 expression were significantly
      associated with poor prognosis. Among clinicopathological parameters,
      overexpression of Jab1 was significantly associated with tumor size and
      International Prognostic Index (IPI), whereas Skp2 expression was significantly
      associated with metastasis and IPI. These findings suggest that the
      overexpression of Jab1 or Skp2 plays an important role in the pathogenesis of
      NHL. Thus, the expression of p27Kip1, Jab1 and Skp2 provided a clinical reference
      for the treatment of NHL.

PMID- 27703677
TI  - Significant antitumor response of disseminated glioblastoma to bevacizumab
      resulting in long-term clinical remission in a patient with
      encephalocraniocutaneous lipomatosis: A case report.
AB  - The prognosis of recurrent and disseminated glioblastoma is very poor.
      Bevacizumab is an effective established therapy for recurrent glioblastoma
      following treatment with radiotherapy plus temozolomide. However, the efficacy of
      bevacizumab is limited to prolonging progression-free survival, without
      significant prolongation of the overall survival. We herein report a case of
      glioblastoma in a 32-year-old female patient with encephalocraniocutaneous
      lipomatosis (ECCL) that had disseminated following surgical resection and
      subsequent treatment with temozolomide and radiation therapy. The disseminated
      tumors disappeared completely after five courses of bevacizumab therapy.
      Surprisingly, the patient has remained in clinical remission for >2.5 years after
      dissemination by continuing this therapy. To the best of our knowledge, this is
      the first case of long-time clinical remission following glioblastoma
      dissemination and treatment with bevacizumab. In the present case, bevacizumab
      exerted an atypically strong antitumor effect against disseminated glioblastoma
      after multidisciplinary treatments had already been applied. Moreover, this is
      the first report of ECCL associated with a malignant brain tumor.

PMID- 27703678
TI  - Mucinous adenocarcinoma of the bladder: A case report and review of the
      literature.
AB  - Mucinous adenocarcinoma of the bladder is rare. The most common symptoms are
      hematuria, suprapubic pain and dysuria. The patient in the present case was a 59
      year-old female who presented with a tumor sized ~5.0*3.4 cm, located in the
      anterior bladder wall, which was pathologically diagnosed as mucinous bladder
      adenocarcinoma. The stage at presentation was considered to be advanced and
      inoperable, due to extensive local invasion. For this type of cancer, early
      diagnosis is crucial. If the cancer is limited to the bladder, the survival rate
      may exceed 75%. Thus, for patients with confirmed or highly suspicious bladder
      mucinous adenocarcinoma, radical bladder cancer resection is required. The 5-year
      survival rate of this type of cancer is 35-55%. In the present case, the cancer
      of the patient was considered inoperable and 3 months later she succumbed to the
      disease.

PMID- 27703680
TI  - Prevalence and distribution pattern of nodal metastases in advanced ovarian
      cancer.
AB  - The objective of this study was to examine the relevance of pelvic and para
      aortic lymph node involvement and the tumour characteristics affecting nodal
      metastases and survival in primary advanced ovarian cancer. A total of 130
      consecutive patients were retrospectively investigated. All the patients received
      stage-related surgery with pelvic and para-aortic lymphadenectomy. The median
      follow-up was 53.5 months. The clinicopathological parameters and distribution
      pattern of nodal metastases were evaluated. Lymph node metastases were detectable
      in 74.62% of the cases. Overall, both pelvic and para-aortic nodes were affected
      in 35.9% of the patients, whereas 13.3% had metastases only in the pelvic and
      13.3% only in the para-aortic lymph nodes. Histological grade 1/2 and 3, serous
      and endometrioid histology were independent predictors of nodal metastasis.
      Serous and endometrioid cancers have shown a predilection for metastasis to the
      pelvic lymph nodes alone, both to the pelvic and the para-aortic nodes, or the
      para-aortic nodes alone. Overall survival was significantly positively affected
      by serous histology with positive nodes (P=0.043). It is crucial to investigate
      the risk factors and metastatic patterns of such patients in a multicenter
      analysis to evaluate individual subgroups. Prospective studies are required to
      investigate the prognostic effect of lymphadenectomy in advanced ovarian cancer
      and its association with histology and distribution pattern of nodal metastasis.

PMID- 27703681
TI  - Nuclear conversion theory: molecular hydrogen in non-magnetic insulators.
AB  - The hydrogen conversion patterns on non-magnetic solids sensitively depend upon
      the degree of singlet/triplet mixing in the intermediates of the catalytic
      reaction. Three main 'symmetry-breaking' interactions are brought together. In a
      typical channel, the electron spin-orbit (SO) couplings introduce some magnetic
      excitations in the non-magnetic solid ground state. The electron spin is
      exchanged with a molecular one by the electric molecule-solid electron repulsion,
      mixing the bonding and antibonding states and affecting the molecule rotation.
      Finally, the magnetic hyperfine contact transfers the electron spin angular
      momentum to the nuclei. Two families of channels are considered and a simple
      criterion based on the SO coupling strength is proposed to select the most
      efficient one. The denoted 'electronic' conversion path involves an emission of
      excitons that propagate and disintegrate in the bulk. In the other denoted
      'nuclear', the excited electron states are transients of a loop, and the electron
      system returns to its fundamental ground state. The described model enlarges
      previous studies by extending the electron basis to charge-transfer states and
      'continui' of band states, and focuses on the broadening of the antibonding
      molecular excited state by the solid conduction band that provides efficient
      tunnelling paths for the hydrogen conversion. After working out the general
      conversion algebra, the conversion rates of hydrogen on insulating and
      semiconductor solids are related to a few molecule-solid parameters (gap width,
      ionization and affinity potentials) and compared with experimental measures.

PMID- 27703679
TI  - Prognostic impact of primary tumor SUVmax on preoperative 18F-fluoro-2-deoxy-D
      glucose positron emission tomography and computed tomography in endometrial
      cancer and uterine carcinosarcoma.
AB  - The objective of the present study was to investigate the usefulness of the
      maximum standardized uptake value (SUVmax) of the primary tumor on preoperative
      18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed
      tomography (PET/CT) as a prognostic indicator in patients with endometrial
      neoplasms. A total of 75 patients with endometrial cancer or uterine
      carcinosarcoma who underwent surgical treatment were included in the present
      study. All patients underwent preoperative PET/CT, and the correlation between
      the SUVmax of the primary tumor and clinical outcomes was analyzed. The SUVmax
      was significantly higher in patients with stage II/III disease, a histology of
      grade 3 endometrioid adenocarcinoma and carcinosarcoma, a positive lymph node
      (LN) status, positive lymph-vascular space involvement (LVSI), and deep (>=1/2)
      myometrial invasion. Receiver operating characteristic curve analysis revealed
      that the optimal cut-off values of SUVmax for predicting a positive LN, LVSI and
      deep myometrial invasion were 7.49, 6.45 and 6.45, respectively. The overall
      survival (OS) and progression-free survival (PFS) of patients with a high SUVmax
      were significantly lower compared with those of patients with a low SUVmax using
      the cut-off value of 7.30. However, no significant difference was observed in the
      OS or PFS between the high and low SUVmax groups when analyzed in carcinosarcoma
      patients alone. Finally, multivariate analyses demonstrated that the SUVmax of
      the primary tumor was an independent prognostic factor for impaired PFS in 55
      endometrioid adenocarcinoma patients; however, not in all patients, including
      those with carcinosarcoma. The present findings demonstrated that the SUVmax of
      the primary tumor may be a useful biomarker for predicting clinical outcomes of
      patients with endometrial cancer, although its prognostic impact appears to be
      limited in patients with uterine carcinosarcoma.

PMID- 27703682
TI  - A modified predator-prey model for the interaction of police and gangs.
AB  - A modified predator-prey model with transmissible disease in both the predator
      and prey species is proposed and analysed, with infected prey being more
      vulnerable to predation and infected predators hunting at a reduced rate. Here,
      the predators are the police and the prey the gang members. In this system, we
      examine whether police control of gangs is possible. The system is analysed with
      the help of stability analyses and numerical simulations. The system has five
      steady states-four of which involve no core gang members and one in which all the
      populations coexist. Thresholds are identified which determine when the predator
      and prey populations survive and when the disease remains endemic. For parameter
      values where the spread of disease among the police officers is greater than the
      death of the police officers, the diseased predator population survives, when it
      would otherwise become extinct.

PMID- 27703683
TI  - Silver-catalysed azide-alkyne cycloaddition (AgAAC): assessing the mechanism by
      density functional theory calculations.
AB  - 'Click reactions' are the copper catalysed dipolar cycloaddition reaction of
      azides and alkynes to incorporate nitrogens into a cyclic hydrocarbon scaffold
      forming a triazole ring. Owing to its efficiency and versatility, this reaction
      and the products, triazole-containing heterocycles, have immense importance in
      medicinal chemistry. Copper is the only known catalyst to carry out this
      reaction, the mechanism of which remains unclear. We report here that the 'click
      reactions' can also be catalysed by silver halides in non-aqueous medium. It
      constitutes an alternative to the well-known CuAAC click reaction. The yield of
      the reaction varies on the type of counter ion present in the silver salt. This
      reaction exhibits significant features, such as high regioselectivity, mild
      reaction conditions, easy availability of substrates and reasonably good yields.
      In this communication, the findings of a new catalyst along with the effect of
      solvent and counter ions will help to decipher the still obscure mechanism of
      this important reaction.

PMID- 27703684
TI  - Patterns and biases in climate change research on amphibians and reptiles: a
      systematic review.
AB  - Climate change probably has severe impacts on animal populations, but
      demonstrating a causal link can be difficult because of potential influences by
      additional factors. Assessing global impacts of climate change effects may also
      be hampered by narrow taxonomic and geographical research foci. We review studies
      on the effects of climate change on populations of amphibians and reptiles to
      assess climate change effects and potential biases associated with the body of
      work that has been conducted within the last decade. We use data from 104 studies
      regarding the effect of climate on 313 species, from 464 species-study
      combinations. Climate change effects were reported in 65% of studies. Climate
      change was identified as causing population declines or range restrictions in
      half of the cases. The probability of identifying an effect of climate change
      varied among regions, taxa and research methods. Climatic effects were equally
      prevalent in studies exclusively investigating climate factors (more than 50% of
      studies) and in studies including additional factors, thus bolstering confidence
      in the results of studies exclusively examining effects of climate change. Our
      analyses reveal biases with respect to geography, taxonomy and research question,
      making global conclusions impossible. Additional research should focus on under
      represented regions, taxa and questions. Conservation and climate policy should
      consider the documented harm climate change causes reptiles and amphibians.

PMID- 27703685
TI  - Fossil clam shells reveal unintended carbon cycling consequences of Colorado
      River management.
AB  - Water management that alters riverine ecosystem processes has strongly influenced
      deltas and the people who depend on them, but a full accounting of the trade-offs
      is still emerging. Using palaeoecological data, we document a surprising
      biogeochemical consequence of water management in the Colorado River basin.
      Complete allocation and consumptive use of the river's flow has altered the
      downstream estuarine ecosystem, including the abundance and composition of the
      mollusc community, an important component in estuarine carbon cycling. In
      particular, population declines in the endemic Colorado delta clam, Mulinia
      coloradoensis, from 50--125 individuals m-2 in the pre-dam era to three
      individuals m-2 today, have likely resulted in a reduction, on the order of 5900
      15 000 t C yr-1 (4.1-10.6 mol C m-2 yr-1), in the net carbon emissions associated
      with molluscs. Although this reduction is large within the estuarine system, it
      is small in comparison with annual global carbon emissions. Nonetheless, this
      finding highlights the need for further research into the effects of dams,
      diversions and reservoirs on the biogeochemistry of deltas and estuaries
      worldwide, underscoring a present need for integrated water and carbon planning.

PMID- 27703686
TI  - Prevalence rates of health and welfare conditions in broiler chickens change with
      weather in a temperate climate.
AB  - Climate change impact assessment and adaptation research in agriculture has
      focused primarily on crop production, with less known about the potential impacts
      on livestock. We investigated how the prevalence of health and welfare conditions
      in broiler (meat) chickens changes with weather (temperature, rainfall, air
      frost) in a temperate climate. Cases of 16 conditions were recorded at approved
      slaughterhouses in Great Britain. National prevalence rates and distribution
      mapping were based on data from more than 2.4 billion individuals, collected
      between January 2011 and December 2013. Analysis of temporal distribution and
      associations with national weather were based on monthly data from more than 6.8
      billion individuals, collected between January 2003 and December 2013. Ascites,
      bruising/fractures, hepatitis and abnormal colour/fever were most common, at
      annual average rates of 29.95, 28.00, 23.76 and 22.29 per 10 000, respectively.
      Ascites and abnormal colour/fever demonstrated clear annual cycles, with higher
      rates in winter than in summer. Ascites prevalence correlated strongly with
      maximum temperature at 0 and -1 month lags. Abnormal colour/fever correlated
      strongly with temperature at 0 lag. Maximum temperatures of approximately 8
      degrees C and approximately 19 degrees C marked the turning points of curve in a
      U-shaped relationship with mortality during transportation and lairage. Future
      climate change research on broilers should focus on preslaughter mortality.

PMID- 27703687
TI  - Social learning solves the problem of narrow-peaked search landscapes:
      experimental evidence in humans.
AB  - The extensive use of social learning is considered a major reason for the
      ecological success of humans. Theoretical considerations, models and experiments
      have explored the evolutionary basis of social learning, showing the conditions
      under which learning from others is more adaptive than individual learning. Here
      we present an extension of a previous experimental set-up, in which individuals
      go on simulated 'hunts' and their success depends on the features of a 'virtual
      arrowhead' they design. Individuals can modify their arrowhead either by
      individual trial and error or by copying others. We study how, in a multimodal
      adaptive landscape, the smoothness of the peaks influences learning. We compare
      narrow peaks, in which solutions close to optima do not provide useful feedback
      to individuals, to wide peaks, where smooth landscapes allow an effective hill
      climbing individual learning strategy. We show that individual learning is more
      difficult in narrow-peaked landscapes, but that social learners perform almost
      equally well in both narrow- and wide-peaked search spaces. There was a weak
      trend for more copying in the narrow than wide condition, although as in previous
      experiments social information was generally underutilized. Our results highlight
      the importance of tasks' design space when studying the adaptiveness of high
      fidelity social learning.

PMID- 27703688
TI  - Differential phenotypic and genetic expression of defence compounds in a plant
      herbivore interaction along elevation.
AB  - Elevation gradients impose large differences in abiotic and biotic conditions
      over short distances, in turn, likely driving differences in gene expression more
      than would genetic variation per se, as natural selection and drift are less
      likely to fix alleles at such a narrow spatial scale. As elevation increases, the
      pressure exerted on plants by herbivores and on arthropod herbivores by predators
      decreases, and organisms spanning the elevation gradient are thus expected to
      show lower levels of defence at high elevation. The alternative hypothesis, based
      on the optimal defence theory, is that defence allocation should be higher in low
      resource habitats such as those at high elevation, due to higher costs associated
      with tissue replacement. In this study, we analyse variation with elevation in
      (i) defence compound content in the plant Lotus corniculatus and (ii) gene
      expression associated with defence against predators in the specific phytophagous
      moth, Zygaena filipendulae. Both species produce cyanogenic glycosides (CNglcs)
      such as lotaustralin and linamarin as defence mechanisms, with the moth, in
      addition, being able to sequester CNglcs from its host plant. Specifically, we
      tested the assumption that the defence-associated phenotype in plants and the
      gene expression in the insect herbivore should covary between low- and high
      elevation environments. We found that L. corniculatus accumulated more CNglcs at
      high elevation, a result in agreement with the optimal defence theory. By
      contrast, we found that the levels of expression in the defence genes of Z.
      filipendulae larvae were not related to the CNglc content of their host plant.
      Overall, expression levels were not correlated with elevation either, with the
      exception of the UGT33A1 gene, which showed a marginally significant trend
      towards higher expression at high elevation when using a simple statistical
      framework. These results suggest that the defence phenotype of plants against
      herbivores, and subsequent herbivore sequestration machineries and de novo
      production, are based on a complex network of interactions.

PMID- 27703689
TI  - Importance of metabolic rate to the relationship between the number of genes in a
      functional category and body size in Peto's paradox for cancer.
AB  - Elucidation of tumour suppression mechanisms is a major challenge in cancer
      biology. Therefore, Peto's paradox, or low cancer incidence in large animals, has
      attracted focus. According to the gene-abundance hypothesis, which considers the
      increase/decrease in cancer-related genes with body size, researchers evaluated
      the associations between gene abundance and body size. However, previous studies
      only focused on a few specific gene functions and have ignored the alternative
      hypothesis (metabolic rate hypothesis): in this hypothesis, the cellular
      metabolic rate and subsequent oxidative stress decreases with increasing body
      size. In this study, we have elected to explore the gene-abundance hypothesis
      taking into account the metabolic rate hypothesis. Thus, we comprehensively
      investigated the correlation between the number of genes in various functional
      categories and body size while at the same time correcting for the mass-specific
      metabolic rate (Bc). A number of gene functions that correlated with body size
      were initially identified, but they were found to be artefactual due to the
      decrease in Bc with increasing body size. By contrast, immune system-related
      genes were found to increase with increasing body size when the correlation
      included this correction for Bc. These findings support the gene-abundance
      hypothesis and emphasize the importance of also taking into account the metabolic
      rate when evaluating gene abundance-body size relationships. This finding may be
      useful for understanding cancer evolution and tumour suppression mechanisms as
      well as for determining cancer-related genes and functions.

PMID- 27703690
TI  - Monocular blur alters the tuning characteristics of stereopsis for spatial
      frequency and size.
AB  - Our sense of depth perception is mediated by spatial filters at different scales
      in the visual brain; low spatial frequency channels provide the basis for coarse
      stereopsis, whereas high spatial frequency channels provide for fine stereopsis.
      It is well established that monocular blurring of vision results in decreased
      stereoacuity. However, previous studies have used tests that are broadband in
      their spatial frequency content. It is not yet entirely clear how the processing
      of stereopsis in different spatial frequency channels is altered in response to
      binocular input imbalance. Here, we applied a new stereoacuity test based on
      narrow-band Gabor stimuli. By manipulating the carrier spatial frequency, we were
      able to reveal the spatial frequency tuning of stereopsis, spanning from coarse
      to fine, under blurred conditions. Our findings show that increasing monocular
      blur elevates stereoacuity thresholds 'selectively' at high spatial frequencies,
      gradually shifting the optimum frequency to lower spatial frequencies.
      Surprisingly, stereopsis for low frequency targets was only mildly affected even
      with an acuity difference of eight lines on a standard letter chart. Furthermore,
      we examined the effect of monocular blur on the size tuning function of
      stereopsis. The clinical implications of these findings are discussed.

PMID- 27703691
TI  - Cytoskeletal architecture and its evolutionary significance in amoeboid
      eukaryotes and their mode of locomotion.
AB  - The cytoskeleton is the hallmark of eukaryotic evolution. The molecular and
      architectural aspects of the cytoskeleton have been playing a prominent role in
      our understanding of the origin and evolution of eukaryotes. In this study, we
      seek to investigate the cytoskeleton architecture and its evolutionary
      significance in understudied amoeboid lineages belonging to Amoebozoa. These
      amoebae primarily use cytoplasmic extensions supported by the cytoskeleton to
      perform important cellular processes such as movement and feeding. Amoeboid
      structure has important taxonomic significance, but, owing to techniques used,
      its potential significance in understanding diversity of the group has been
      seriously compromised, leading to an under-appreciation of its value. Here, we
      used immunocytochemistry and confocal microscopy to study the architecture of
      microtubules (MTs) and F-actin in diverse groups of amoebae. Our results
      demonstrate that all Amoebozoa examined are characterized by a complex
      cytoskeletal array, unlike what has been previously thought to exist. Our results
      not only conclusively demonstrate that all amoebozoans possess complex
      cytoplasmic MTs, but also provide, for the first time, a potential synapomorphy
      for the molecularly defined Amoebozoa clade. Based on this evidence, the last
      common ancestor of amoebozoans is hypothesized to have had a complex interwoven
      MT architecture limited within the granular cell body. We also generate several
      cytoskeleton characters related to MT and F-actin, which are found to be robust
      for defining groups in deep and shallow nodes of Amoebozoa.

PMID- 27703692
TI  - Geochemistry, faunal composition and trophic structure in reducing sediments on
      the southwest South Georgia margin.
AB  - Despite a number of studies in areas of focused methane seepage, the extent of
      transitional sediments of more diffuse methane seepage, and their influence upon
      biological communities is poorly understood. We investigated an area of reducing
      sediments with elevated levels of methane on the South Georgia margin around 250
      m depth and report data from a series of geochemical and biological analyses.
      Here, the geochemical signatures were consistent with weak methane seepage and
      the role of sub-surface methane consumption was clearly very important,
      preventing gas emissions into bottom waters. As a result, the contribution of
      methane-derived carbon to the microbial and metazoan food webs was very limited,
      although sulfur isotopic signatures indicated a wider range of dietary
      contributions than was apparent from carbon isotope ratios. Macrofaunal
      assemblages had high dominance and were indicative of reducing sediments, with
      many taxa common to other similar environments and no seep-endemic fauna,
      indicating transitional assemblages. Also similar to other cold seep areas, there
      were samples of authigenic carbonate, but rather than occurring as pavements or
      sedimentary concretions, these carbonates were restricted to patches on the
      shells of Axinulus antarcticus (Bivalvia, Thyasiridae), which is suggestive of
      microbe-metazoan interactions.

PMID- 27703694
TI  - Emotional arousal when watching drama increases pain threshold and social
      bonding.
AB  - Fiction, whether in the form of storytelling or plays, has a particular
      attraction for us: we repeatedly return to it and are willing to invest money and
      time in doing so. Why this is so is an evolutionary enigma that has been
      surprisingly underexplored. We hypothesize that emotionally arousing drama, in
      particular, triggers the same neurobiological mechanism (the endorphin system,
      reflected in increased pain thresholds) that underpins anthropoid primate and
      human social bonding. We show that, compared to subjects who watch an emotionally
      neutral film, subjects who watch an emotionally arousing film have increased pain
      thresholds and an increased sense of group bonding.

PMID- 27703693
TI  - A computational study of cancer hyperthermia based on vascular magnetic
      nanoconstructs.
AB  - The application of hyperthermia to cancer treatment is studied using a novel
      model arising from the fundamental principles of flow, mass and heat transport in
      biological tissues. The model is defined at the scale of the tumour
      microenvironment and an advanced computational scheme called the embedded
      multiscale method is adopted to solve the governing equations. More precisely,
      this approach involves modelling capillaries as one-dimensional channels carrying
      flow, and special mathematical operators are used to model their interaction with
      the surrounding tissue. The proposed computational scheme is used to analyse
      hyperthermic treatment of cancer based on systemically injected vascular magnetic
      nanoconstructs carrying super-paramagnetic iron oxide nanoparticles. An
      alternating magnetic field is used to excite the nanoconstructs and generate
      localized heat within the tissue. The proposed model is particularly adequate for
      this application, since it has a unique capability of incorporating
      microvasculature configurations based on physiological data combined with coupled
      capillary flow, interstitial filtration and heat transfer. A virtual tumour model
      is initialized and the spatio-temporal distribution of nanoconstructs in the
      vascular network is analysed. In particular, for a reference iron oxide
      concentration, temperature maps of several different hypothesized treatments are
      generated in the virtual tumour model. The observations of the current study
      might in future guide the design of more efficient treatments for cancer
      hyperthermia.

PMID- 27703695
TI  - US line-ups outperform UK line-ups.
AB  - In the USA and the UK, many thousands of police suspects are identified by
      eyewitnesses every year. Unfortunately, many of those suspects are innocent,
      which becomes evident when they are exonerated by DNA testing, often after having
      been imprisoned for years. It is, therefore, imperative to use identification
      procedures that best enable eyewitnesses to discriminate innocent from guilty
      suspects. Although police investigators in both countries often administer line
      up procedures, the details of how line-ups are presented are quite different and
      an important direct comparison has yet to be conducted. We investigated whether
      these two line-up procedures differ in terms of (i) discriminability (using
      receiver operating characteristic analysis) and (ii) reliability (using
      confidence-accuracy characteristic analysis). A total of 2249 participants
      watched a video of a crime and were later tested using either a six-person
      simultaneous photo line-up procedure (USA) or a nine-person sequential video line
      up procedure (UK). US line-up procedure yielded significantly higher
      discriminability and significantly higher reliability. The results do not
      pinpoint the reason for the observed difference between the two procedures, but
      they do suggest that there is much room for improvement with the UK line-up.

PMID- 27703696
TI  - A novel MC1R allele for black coat colour reveals the Polynesian ancestry and
      hybridization patterns of Hawaiian feral pigs.
AB  - Pigs (Sus scrofa) have played an important cultural role in Hawaii since
      Polynesians first introduced them in approximately AD 1200. Additional varieties
      of pigs were introduced following Captain Cook's arrival in Hawaii in 1778 and it
      has been suggested that the current pig population may descend primarily, or even
      exclusively, from European pigs. Although populations of feral pigs today are an
      important source of recreational hunting on all of the major islands, they also
      negatively impact native plants and animals. As a result, understanding the
      origins of these feral pig populations has significant ramifications for
      discussions concerning conservation management, identity and cultural continuity
      on the islands. Here, we analysed a neutral mitochondrial marker and a functional
      nuclear coat colour marker in 57 feral Hawaiian pigs. Through the identification
      of a new mutation in the MC1R gene that results in black coloration, we
      demonstrate that Hawaiian feral pigs are mostly the descendants of those
      originally introduced during Polynesian settlement, though there is evidence for
      some admixture. As such, extant Hawaiian pigs represent a unique historical
      lineage that is not exclusively descended from feral pigs of European origin.

PMID- 27703697
TI  - Acidification and gamma-aminobutyric acid independently alter kairomone-induced
      behaviour.
AB  - Exposure to high pCO2 or low pH alters sensation and behaviour in many marine
      animals. We show that crab larvae lose their ability to detect and/or process
      predator kairomones after exposure to low pH over a time scale relevant to diel
      pH cycles in coastal environments. Previous work suggests that acidification
      affects sensation and behaviour through altered neural function, specifically the
      action of gamma-aminobutyric acid (GABA), because a GABA antagonist, gabazine,
      restores the original behaviour. Here, however, gabazine resulted in a loss of
      kairomone detection/processing, regardless of pH. Our results also suggest that
      GABAergic signalling is necessary for kairomone identification in these larvae.
      Hence, the mechanism for the observed pH effect varies from the original GABA
      hypothesis. Furthermore, we suggest that this pH effect is adaptive under diel
      cycling pH.

PMID- 27703698
TI  - Seabird diving behaviour reveals the functional significance of shelf-sea fronts
      as foraging hotspots.
AB  - Oceanic fronts are key habitats for a diverse range of marine predators, yet how
      they influence fine-scale foraging behaviour is poorly understood. Here, we
      investigated the dive behaviour of northern gannets Morus bassanus in relation to
      shelf-sea fronts. We GPS (global positioning system) tracked 53 breeding birds
      and examined the relationship between 1901 foraging dives (from time-depth
      recorders) and thermal fronts (identified via Earth Observation composite front
      mapping) in the Celtic Sea, Northeast Atlantic. We (i) used a habitat-use
      availability analysis to determine whether gannets preferentially dived at
      fronts, and (ii) compared dive characteristics in relation to fronts to
      investigate the functional significance of these oceanographic features. We found
      that relationships between gannet dive probabilities and fronts varied by frontal
      metric and sex. While both sexes were more likely to dive in the presence of
      seasonally persistent fronts, links to more ephemeral features were less clear.
      Here, males were positively correlated with distance to front and cross-front
      gradient strength, with the reverse for females. Both sexes performed two dive
      strategies: shallow V-shaped plunge dives with little or no active swim phase
      (92% of dives) and deeper U-shaped dives with an active pursuit phase of at least
      3 s (8% of dives). When foraging around fronts, gannets were half as likely to
      engage in U-shaped dives compared with V-shaped dives, independent of sex.
      Moreover, V-shaped dive durations were significantly shortened around fronts.
      These behavioural responses support the assertion that fronts are important
      foraging habitats for marine predators, and suggest a possible mechanistic link
      between the two in terms of dive behaviour. This research also emphasizes the
      importance of cross-disciplinary research when attempting to understand marine
      ecosystems.

PMID- 27703699
TI  - Temporal regularity increases with repertoire complexity in the Australian pied
      butcherbird's song.
AB  - Music maintains a characteristic balance between repetition and novelty. Here, we
      report a similar balance in singing performances of free-living Australian pied
      butcherbirds. Their songs include many phrase types. The more phrase types in a
      bird's repertoire, the more diverse the singing performance can be. However,
      without sufficient temporal organization, avian listeners may find diverse
      singing performances difficult to perceive and memorize. We tested for a
      correlation between the complexity of song repertoire and the temporal regularity
      of singing performance. We found that different phrase types often share motifs
      (notes or stereotyped groups of notes). These shared motifs reappeared in
      strikingly regular temporal intervals across different phrase types, over
      hundreds of phrases produced without interruption by each bird. We developed a
      statistical estimate to quantify the degree to which phrase transition structure
      is optimized for maximizing the regularity of shared motifs. We found that
      transition probabilities between phrase types tend to maximize regularity in the
      repetition of shared motifs, but only in birds of high repertoire complexity.
      Conversely, in birds of low repertoire complexity, shared motifs were produced
      with less regularity. The strong correlation between repertoire complexity and
      motif regularity suggests that birds possess a mechanism that regulates the
      temporal placement of shared motifs in a manner that takes repertoire complexity
      into account. We discuss alternative musical, mechanistic and ecological
      explanations to this effect.

PMID- 27703700
TI  - Enhancing endorsement of scientific inquiry increases support for pro-environment
      policies.
AB  - Pro-environment policies require public support and engagement, but in countries
      such as the USA, public support for pro-environment policies remains low.
      Increasing public scientific literacy is unlikely to solve this, because
      increased scientific literacy does not guarantee increased acceptance of critical
      environmental issues (e.g. that climate change is occurring). We distinguish
      between scientific literacy (basic scientific knowledge) and endorsement of
      scientific inquiry (perceiving science as a valuable way of accumulating
      knowledge), and examine the relationship between people's endorsement of
      scientific inquiry and their support for pro-environment policy. Analysis of a
      large, publicly available dataset shows that support for pro-environment policies
      is more strongly related to endorsement of scientific inquiry than to scientific
      literacy among adolescents. An experiment demonstrates that a brief intervention
      can increase support for pro-environment policies via increased endorsement of
      scientific inquiry among adults. Public education about the merits of scientific
      inquiry may facilitate increased support for pro-environment policies.

PMID- 27703701
TI  - Energy-based constitutive modelling of local material properties of canine
      aortas.
AB  - This study aims at determining the in vitro anisotropic mechanical behaviour of
      canine aortic tissue. We specifically focused on spatial variations of these
      properties along the axis of the vessel. We performed uniaxial stretch tests on
      canine aortic samples in both circumferential and longitudinal directions, as
      well as histological examinations to derive the tissue's fibre orientations. We
      subsequently characterized a constitutive model that incorporates both
      phenomenological and structural elements to account for macroscopic and
      microstructural behaviour of the tissue. We showed the two fibre families were
      oriented at similar angles with respect to the aorta's axis. We also found
      significant changes in mechanical behaviour of the tissue as a function of axial
      position from proximal to distal direction: the fibres become more aligned with
      the aortic axis from 46 degrees  to 30 degrees . Also, the linear shear modulus
      of media decreased as we moved distally along the aortic axis from 139 to 64 kPa.
      These changes derived from the parameters in the nonlinear constitutive model
      agreed well with the changes in tissue structure. In addition, we showed that
      isotropic contribution, carried by elastic lamellae, to the total stress induced
      in the tissue decreases at higher stretch ratios, whereas anisotropic stress,
      carried by collagen fibres, increases. The constitutive models can be readily
      used to design computational models of tissue deformation during physiological
      loading cycles. The findings of this study extend the understanding of local
      mechanical properties that could lead to region-specific diagnostics and
      treatment of arterial diseases.

PMID- 27703702
TI  - Colour vision and background adaptation in a passerine bird, the zebra finch
      (Taeniopygia guttata).
AB  - Today, there is good knowledge of the physiological basis of bird colour vision
      and how mathematical models can be used to predict visual thresholds. However, we
      still know only little about how colour vision changes between different viewing
      conditions. This limits the understanding of how colour signalling is configured
      in habitats where the light of the illumination and the background may shift
      dramatically. I examined how colour discrimination in zebra finch (Taeniopygia
      guttata) is affected by adaptation to different backgrounds. I trained finches in
      a two-alternative choice task, to choose between red discs displayed on
      backgrounds with different colours. I found that discrimination thresholds
      correlate with stimulus contrast to the background. Thresholds are low, and in
      agreement with model predictions, for a background with a red colour similar to
      the discs. For the most contrasting green background, thresholds are about five
      times higher than this. Subsequently, I trained the finches for the detection of
      single discs on a grey background. Detection thresholds are about 2.5 to 3 times
      higher than discrimination thresholds. This study demonstrates close similarities
      in human and bird colour vision, and the quantitative data offer a new
      possibility to account for shifting viewing conditions in colour vision models.

PMID- 27703703
TI  - The natural selection of bad science.
AB  - Poor research design and data analysis encourage false-positive findings. Such
      poor methods persist despite perennial calls for improvement, suggesting that
      they result from something more than just misunderstanding. The persistence of
      poor methods results partly from incentives that favour them, leading to the
      natural selection of bad science. This dynamic requires no conscious strategizing
      no deliberate cheating nor loafing-by scientists, only that publication is a
      principal factor for career advancement. Some normative methods of analysis have
      almost certainly been selected to further publication instead of discovery. In
      order to improve the culture of science, a shift must be made away from
      correcting misunderstandings and towards rewarding understanding. We support this
      argument with empirical evidence and computational modelling. We first present a
      60-year meta-analysis of statistical power in the behavioural sciences and show
      that power has not improved despite repeated demonstrations of the necessity of
      increasing power. To demonstrate the logical consequences of structural
      incentives, we then present a dynamic model of scientific communities in which
      competing laboratories investigate novel or previously published hypotheses using
      culturally transmitted research methods. As in the real world, successful labs
      produce more 'progeny,' such that their methods are more often copied and their
      students are more likely to start labs of their own. Selection for high output
      leads to poorer methods and increasingly high false discovery rates. We
      additionally show that replication slows but does not stop the process of
      methodological deterioration. Improving the quality of research requires change
      at the institutional level.

PMID- 27703704
TI  - Colour thresholds in a coral reef fish.
AB  - Coral reef fishes are among the most colourful animals in the world. Given the
      diversity of lifestyles and habitats on the reef, it is probable that in many
      instances coloration is a compromise between crypsis and communication. However,
      human observation of this coloration is biased by our primate visual system. Most
      animals have visual systems that are 'tuned' differently to humans; optimized for
      different parts of the visible spectrum. To understand reef fish colours, we need
      to reconstruct the appearance of colourful patterns and backgrounds as they are
      seen through the eyes of fish. Here, the coral reef associated triggerfish,
      Rhinecanthus aculeatus, was tested behaviourally to determine the limits of its
      colour vision. This is the first demonstration of behavioural colour
      discrimination thresholds in a coral reef species and is a critical step in our
      understanding of communication and speciation in this vibrant colourful habitat.
      Fish were trained to discriminate between a reward colour stimulus and series of
      non-reward colour stimuli and the discrimination thresholds were found to
      correspond well with predictions based on the receptor noise limited visual model
      and anatomy of the eye. Colour discrimination abilities of both reef fish and a
      variety of animals can therefore now be predicted using the parameters described
      here.

PMID- 27703705
TI  - Mathematical toy model inspired by the problem of the adaptive origins of the
      sexual orientation continuum.
AB  - Same-sex sexual behaviour is ubiquitous in the animal kingdom, but its adaptive
      origins remain a prominent puzzle. Here, I suggest the possibility that same-sex
      sexual behaviour arises as a consequence of the competition between an
      evolutionary drive for a wide diversity in traits, which improves the
      adaptability of a population, and a drive for sexual dichotomization of traits,
      which promotes opposite-sex attraction and increases the rate of reproduction.
      This trade-off is explored via a simple mathematical 'toy model'. The model
      exhibits a number of interesting features and suggests a simple mathematical form
      for describing the sexual orientation continuum.

PMID- 27703707
TI  - Packing and deploying Soft Origami to and from cylindrical volumes with
      application to automotive airbags.
AB  - Packing soft-sheet materials of approximately zero bending stiffness using Soft
      Origami (origami patterns applied to soft-sheet materials) into cylindrical
      volumes and their deployment via mechanisms or internal pressure (inflation) is
      of interest in fields including automobile airbags, deployable heart stents,
      inflatable space habitats, and dirigible and parachute packing. This paper
      explores twofold patterns, the 'flasher' and the 'inverted-cone fold', for
      packing soft-sheet materials into cylindrical volumes. Two initial packing
      methods and mechanisms are examined for each of the flasher and inverted-cone
      fold patterns. An application to driver's side automobile airbags is performed,
      and deployment tests are completed to compare the influence of packing method and
      origami pattern on deployment performance. Following deployment tests, two
      additional packing methods for the inverted-cone fold pattern are explored and
      applied to automobile airbags. It is shown that modifying the packing method
      (using different methods to impose the same base pattern on the soft-sheet
      material) can lead to different deployment performance. In total, two origami
      patterns and six packing methods are examined, and the benefits of using Soft
      Origami patterns and packing methods are discussed. Soft Origami is presented as
      a viable method for efficiently packing soft-sheet materials into cylindrical
      volumes.

PMID- 27703706
TI  - The secret life of ground squirrels: accelerometry reveals sex-dependent
      plasticity in above-ground activity.
AB  - The sexes differ in how and when they allocate energy towards reproduction, but
      how this influences phenotypic plasticity in daily activity patterns is unclear.
      Here, we use collar-mounted light loggers and triaxial accelerometers to examine
      factors that affect time spent above ground and overall dynamic body acceleration
      (ODBA), an index of activity-specific energy expenditure, across the active
      season of free-living, semi-fossorial arctic ground squirrels (Urocitellus
      parryii). We found high day-to-day variability in time spent above ground and
      ODBA with most of the variance explained by environmental conditions known to
      affect thermal exchange. In both years, females spent more time below ground
      compared with males during parturition and early lactation; however, this
      difference was fourfold larger in the second year, possibly, because females were
      in better body condition. Daily ODBA positively correlated with time spent above
      ground in both sexes, but females were more active per unit time above ground.
      Consequently, daily ODBA did not differ between the sexes when females were early
      in lactation, even though females were above ground three to six fewer hours each
      day. Further, on top of having the additional burden of milk production, ODBA
      data indicate females also had fragmented rest patterns and were more active
      during late lactation. Our results indicate that sex differences in reproductive
      requirements can have a substantial influence on activity patterns, but the size
      of this effect may be dependent on capital resources accrued during gestation.

PMID- 27703709
TI  - Atypical residency of short-beaked common dolphins (Delphinus delphis) to a
      shallow, urbanized embayment in south-eastern Australia.
AB  - Short-beaked common dolphins (Delphinus delphis) are typically considered highly
      mobile, offshore delphinids. This study assessed the residency of a small
      community of short-beaked common dolphins in the shallow, urbanized Port Phillip
      Bay, south-eastern Australia. The ability to identify common dolphins by their
      dorsal fin markings and coloration using photo-identification was also
      investigated. Systematic and non-systematic boat surveys were undertaken between
      2007 and 2014. Results showed that 13 adult common dolphins and their offspring
      inhabit Port Phillip Bay, of which 10 adults exhibit residency to the bay. The
      majority of these adults are reproductively active females, suggesting that
      female philopatry may occur in the community. Systematic surveys conducted
      between 2012 and 2014 revealed that the dolphins were found in a median water
      depth of 16 m and median distance of 2.2 km from the coast. The shallow,
      urbanized habitat of this resident common dolphin community is atypical for this
      species. As a result, these common dolphins face threats usually associated with
      inshore bottlenose dolphin communities. We suggest that the Port Phillip Bay
      common dolphin community is considered and managed separate to those outside the
      embayment and offshore to ensure the community's long-term viability and
      residency in the bay.

PMID- 27703708
TI  - The first iguanian lizard from the Mesozoic of Africa.
AB  - The fossil record shows that iguanian lizards were widely distributed during the
      Late Cretaceous. However, the biogeographic history and early evolution of one of
      its most diverse and peculiar clades (acrodontans) remain poorly known. Here, we
      present the first Mesozoic acrodontan from Africa, which also represents the
      oldest iguanian lizard from that continent. The new taxon comes from the Kem Kem
      Beds in Morocco (Cenomanian, Late Cretaceous) and is based on a partial lower
      jaw. The new taxon presents a number of features that are found only among
      acrodontan lizards and shares greatest similarities with uromastycines,
      specifically. In a combined evidence phylogenetic dataset comprehensive of all
      major acrodontan lineages using multiple tree inference methods (traditional and
      implied weighting maximum-parsimony, and Bayesian inference), we found support
      for the placement of the new species within uromastycines, along with Gueragama
      sulamericana (Late Cretaceous of Brazil). The new fossil supports the previously
      hypothesized widespread geographical distribution of acrodontans in Gondwana
      during the Mesozoic. Additionally, it provides the first fossil evidence of
      uromastycines in the Cretaceous, and the ancestry of acrodontan iguanians in
      Africa.

PMID- 27703710
TI  - A hybrid continuous-discrete method for stochastic reaction-diffusion processes.
AB  - Stochastic fluctuations in reaction-diffusion processes often have substantial
      effect on spatial and temporal dynamics of signal transductions in complex
      biological systems. One popular approach for simulating these processes is to
      divide the system into small spatial compartments assuming that molecules react
      only within the same compartment and jump between adjacent compartments driven by
      the diffusion. While the approach is convenient in terms of its implementation,
      its computational cost may become prohibitive when diffusive jumps occur
      significantly more frequently than reactions, as in the case of rapid diffusion.
      Here, we present a hybrid continuous-discrete method in which diffusion is
      simulated using continuous approximation while reactions are based on the
      Gillespie algorithm. Specifically, the diffusive jumps are approximated as
      continuous Gaussian random vectors with time-dependent means and covariances,
      allowing use of a large time step, even for rapid diffusion. By considering the
      correlation among diffusive jumps, the approximation is accurate for the second
      moment of the diffusion process. In addition, a criterion is obtained for
      identifying the region in which such diffusion approximation is required to
      enable adaptive calculations for better accuracy. Applications to a linear
      diffusion system and two nonlinear systems of morphogens demonstrate the
      effectiveness and benefits of the new hybrid method.

PMID- 27703711
TI  - Sustainable self-healing at ultra-low temperatures in structural composites
      incorporating hollow vessels and heating elements.
AB  - Self-healing composites are able to restore their properties automatically.
      Impressive healing efficiencies can be achieved when conditions are favourable.
      On the other hand, healing might not be possible under adverse circumstances such
      as very low ambient temperature. Here, we report a structural composite able to
      maintain its temperature to provide a sustainable self-healing capability-similar
      to that in the natural world where some animals keep a constant body temperature
      to allow enzymes to stay active. The composite embeds three-dimensional hollow
      vessels with the purpose of delivering and releasing healing agents, and a porous
      conductive element to provide heat internally to defrost and promote healing
      reactions. A healing efficiency over 100% at around -60 degrees C was obtained.
      The effects of the sheets on the interlaminar and tensile properties have been
      investigated experimentally. The proposed technique can be implemented in a
      majority of extrinsic self-healing composites to enable automatic recovery at
      ultra-low temperatures.

PMID- 27703712
TI  - Stretching the truth: length data highlight falsification of Japanese sperm whale
      catch statistics in the Southern Hemisphere.
AB  - Falsification of reports on Japanese catches of sperm whales (Physeter
      macrocephalus) is known to have occurred at both land whaling stations and in
      North Pacific factory fleets. Here, we conduct an analysis of pelagic sperm whale
      catches in the Southern Hemisphere: we compare true Soviet length data from the
      Yuri Dolgorukiy factory fleet during 1960-1975 to data for the same period
      reported to the International Whaling Commission (IWC) by Japan. Prior to
      implementation of the International Observer Scheme (IOS) in 1972, the Soviet
      fleet killed 5536 females, of which only 153 (2.8%) were at or above the minimum
      legal length of 11.6 m. During the same period, Japan killed 5799 females and
      reported that 5686 (98.5%) were of legal size, with 88.5% of the entire length
      distribution reported as being between 11.6 and 12.0 m. This unrealistic
      distribution, together with the fact that Japanese fleets were supposedly able to
      catch 37 times the number of legal-sized females as the Soviet fleet, indicates
      extensive falsification of catch data by Japan. Further evidence of misreporting
      is that females >11.5 m dropped to 9.1% of the Japanese catch after 1971, when
      the IOS made cheating much more difficult. That 99.6% of 10 433 males in the pre
      IOS catch were also reported to be of legal size, indicates that illegal catches
      were not confined to females. We caution that the Japanese sperm whale data in
      the IWC Catch Database are unreliable and should not be used in population
      assessments. The ease with which illegal catches were apparently made underscores
      the past failures of the IWC to effectively regulate whaling.

PMID- 27703713
TI  - Offspring sex preferences among patrilineal and matrilineal Mosuo in Southwest
      China revealed by differences in parity progression.
AB  - Son preference predominates in China, yet there are patterned exceptions to this
      rule. In this paper, we test whether lineality (patrilineal versus matrilineal
      inheritance and descent) is associated with son versus daughter preference among
      the ethnic Mosuo (Na) of Southwest China. Our results show (i) an increased
      probability of continued fertility among matrilineal women after having a son
      compared with a daughter and (ii) an increased probability of continued fertility
      among patrilineal women after having a daughter compared with a son. These
      results are consistent with son preference among patrilineal Mosuo and more muted
      daughter preference among the matrilineal Mosuo. Furthermore, we show (iii) the
      lowest probability of continued fertility at parity 2 once women have one
      daughter and one son across both systems, suggesting that preferences for at
      least one of each sex exist alongside preferences for the lineal sex. The Mosuo
      are the only known small-scale society in which two kinship systems distinguish
      sub-groups with many otherwise shared cultural characteristics. We discuss why
      this, in conjunction with differences in subsistence, may shed light on the
      evolutionary underpinnings of offspring sex preferences.

PMID- 27703714
TI  - Transition from one- to two-dimensional development facilitates maintenance of
      multicellularity.
AB  - Filamentous organisms represent an example where incomplete separation after cell
      division underlies the development of multicellular formations. With a view to
      understanding the evolution of more complex multicellular structures, we explore
      the transition of multicellular growth from one to two dimensions. We develop a
      computational model to simulate multicellular development in populations where
      cells exhibit density-dependent division and death rates. In both the one- and
      two-dimensional contexts, multicellular formations go through a developmental
      cycle of growth and subsequent decay. However, the model shows that a transition
      to a higher dimension increases the size of multicellular formations and
      facilitates the maintenance of large cell clusters for significantly longer
      periods of time. We further show that the turnover rate for cell division and
      death scales with the number of iterations required to reach the stationary
      multicellular size at equilibrium. Although size and life cycles of multicellular
      organisms are affected by other environmental and genetic factors, the model
      presented here evaluates the extent to which the transition of multicellular
      growth from one to two dimensions contributes to the maintenance of multicellular
      structures during development.

PMID- 27703715
TI  - Disclosing the potential impact of placebo controls in antidepressant trials.
AB  - BACKGROUND: Although placebo-control clinical trials that withhold effective
      treatments can be permissible, how best to inform participants of the placebo
      design has received little attention. AIMS: To determine the effect of disclosing
      quantitative outcome estimates of individual treatment v. entering placebo
      control randomised control trial (RCT) on willingness to enrol in such an RCT.
      METHOD: We randomised 278 adult patients at a depression clinic to receive
      standard disclosure (n = 129) or enhanced (n = 149) quantitative outcome
      estimates (based on decision analysis) of individual treatment v. RCT, and
      assessed their willingness to enrol in the RCT. RESULTS: A greater proportion of
      those in the standard arm preferred enrolling in RCT (41.3% v. 23.8%, P = 0.002).
      Those in the standard arm preferred RCT more for direct benefit than altruism
      reasons, whereas the opposite was true in the enhanced arm. CONCLUSIONS:
      Disclosing the quantitative outcome implications of placebos may select for fewer
      but more altruistic participants. DECLARATION OF INTEREST: S.Y.H.K. was a DSMB
      member of a clinical trial sponsored by Hoffman-LaRoche and he receives royalties
      from Oxford University Press for his book Evaluation of Capacity to Consent to
      Treatment and Research. C.M. has served in the past year on a scientific advisory
      board and as a consultant for Janssen Pharmaceuticals. COPYRIGHT AND USAGE: This
      is an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703718
TI  - Borderline personality disorder: patterns of self-harm, reported childhood trauma
      and clinical outcome.
AB  - SUMMARY: Consecutive admissions of 214 women with borderline personality disorder
      were investigated for patterns of specific forms of self-harm and reported
      developmental experiences. Systematic examination of clinical notes found that
      75% had previously reported a history of childhood sexual abuse. These women were
      more likely to self-harm, and in specific ways that may reflect their past
      experiences. Despite this, treatment within a dialectical behaviour therapy
      informed therapeutic community leads to relatively greater clinical gains than
      for those without a reported sexual abuse trauma history. Notably, greater
      behavioural and self-reported distress and dissociation were not found to predict
      poor clinical outcome. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c)
      The Royal College of Psychiatrists 2015. This is an open access article
      distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703716
TI  - Familial risk and childhood adversity interplay in the onset of psychosis.
AB  - BACKGROUND: The association between childhood adversity and psychosis in
      adulthood is well established. However, genetic factors might confound or
      moderate this association. AIMS: Using a catchment-based case-control sample, we
      explored the main effects of, and interplay between, childhood adversity and
      family psychiatric history on the onset of psychosis. METHOD: Childhood adversity
      (parental separation and death, physical and sexual abuse) was assessed
      retrospectively in 224 individuals with a first presentation of psychosis and 256
      community controls from South London, UK. Occurrence of psychotic and affective
      disorders in first-degree relatives was ascertained with the Family Interview for
      Genetic Studies (FIGS). RESULTS: Parental history of psychosis did not confound
      the association between childhood adversity and psychotic disorder. There was no
      evidence that childhood adversity and familial liability combined synergistically
      to increase odds of psychosis beyond the effect of each individually.
      CONCLUSIONS: Our results do not support the hypothesis that family psychiatric
      history amplifies the effect of childhood adversity on odds of psychosis.
      DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2015. This is an open access article distributed under the terms of
      the Creative Commons Attribution (CC BY) licence.

PMID- 27703717
TI  - Unrecognised psychopathology in patients with difficult asthma: major mental and
      personality disorders.
AB  - BACKGROUND: Difficult asthma is a severe subgroup of asthma in which the main
      feature is uncontrollability of symptoms. Psychopathology is suggested to be
      prominent in patients with difficult asthma and considered important in its
      treatment; however, the evidence is scarce. AIMS: To describe psychopathology in
      difficult asthma, both major mental and personality disorders, based on
      diagnostic interviews. METHOD: This study was conducted in a specialised asthma
      care centre. A total of 51 patients with difficult asthma were diagnosed at the
      start of the treatment programme using two structured clinical interviews for
      both major mental (SCID-I) and personality disorders (SCID-II) according to DSM
      IV-TR. RESULTS: About 55% of the patients with difficult asthma had a psychiatric
      disorder of which 89% was undiagnosed and untreated before being interviewed.
      About 49% had a minimum of one major mental disorder of which the cluster of
      anxiety disorders was the most common cluster of major mental disorders, followed
      by somatoform disorders. About 20% were diagnosed with a personality disorder. Of
      the 10 patients with a personality disorder, 9 had an obsessive-compulsive
      personality disorder. CONCLUSIONS: This study demonstrates that more than half of
      patients with difficult asthma had a psychiatric disorder of which 89% was
      unrecognised. This study highlights the importance of offering patients with
      difficult asthma a psychiatric diagnostic interview and/or a psychiatric
      consultation as part of their routine medical examination and provision of
      appropriate psychiatric treatment. Moreover, it highlights the urgency of further
      research into the role of psychopathology in the development of difficult asthma.
      DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2015. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703719
TI  - Validation of the Short Obsessive-Compulsive Disorder Screener (SOCS) in children
      and adolescents.
AB  - BACKGROUND: The Short Obsessive-Compulsive Disorder Screener (SOCS) is
      recommended by the National Institute for Health and Care Excellence as a
      suitable and validated screening tool for 11- to 15-year olds. Despite its
      excellent sensitivity and specificity in detecting obsessive-compulsive disorder
      (OCD), it has limitations. AIMS: To empirically examine whether the SOCS is
      suitable for assessing OCD symptoms across a wide age range of children and
      adolescents and to provide new data about its psychometric properties. METHOD:
      Participants were 94 patients (9-19 years) with OCD, and 880 healthy controls.
      RESULTS: The results supported the SOCS' unidimensional factor structure and
      metric invariance across samples. It showed good reliability in terms of internal
      consistency and temporal stability. Furthermore, it had significantly high
      correlations with other OCD measures and an acceptable sensitivity and
      specificity for detecting OCD. CONCLUSIONS: The SOCS is a brief screening tool
      suitable for detecting OCD in children and adolescents. DECLARATION OF INTEREST:
      None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2015. This is
      an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703720
TI  - Antipsychotics for the management of psychosis in Parkinson's disease: systematic
      review and meta-analysis.
AB  - BACKGROUND: Antipsychotics can exacerbate motor symptoms in Parkinson's disease
      psychosis. AIMS: To systematically review the literature on the efficacy and
      acceptability of antipsychotics for Parkinson's disease psychosis. METHOD:
      Randomised controlled trials comparing an antipsychotic with placebo were
      systematically reviewed. RESULTS: The final selection list included nine studies
      using quetiapine (3), clozapine (2), olanzapine (3) and pimavanserin (1). A
      narrative synthesis and meta-analyses (where appropriate) were presented for each
      antipsychotic. Clozapine demonstrated superiority over placebo in reducing
      psychotic symptoms. Quetiapine and olanzapine did not significantly improve
      psychotic symptoms. All three antipsychotics may exacerbate motor symptoms.
      Quetiapine studies were associated with high drop-out rates due to adverse
      events. Pimavanserin is a novel treatment that warrants further investigation.
      CONCLUSIONS: Further research is needed. Clozapine and pimavanserin appear to be
      a promising treatment for Parkinson's disease psychosis. DECLARATION OF INTEREST:
      None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2015. This is
      an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703722
TI  - Improving quality of care among patients hospitalised with schizophrenia: a
      nationwide initiative.
AB  - BACKGROUND: The effectiveness of systematic quality improvement initiatives in
      psychiatric care remains unclear. AIMS: To examine whether quality of care has
      changed following implementation of a systematic monitoring programme of hospital
      performance measures. METHOD: In a nationwide population-based cohort study, we
      identified 14 228 patients admitted to psychiatric departments between 2004 and
      2011 from The Danish Schizophrenia Registry. The registry systematically monitors
      the adherence to guideline recommended processes of care. RESULTS: The overall
      proportion of all relevant recommended processes of care increased from 64 to 76%
      between 2004 and 2011. The adherence to individual processes of care increased
      over time, including assessment of psychopathology using a diagnostic interview
      (relative risk (RR): 2.01, 95% CI: 1.51-2.68), contact with relatives (RR: 1.44,
      95% CI: 1.27-1.62), psychoeducation (RR: 1.33, 95% CI: 1.19-1.48), psychiatric
      aftercare (RR: 1.06, 95% CI: 1.01-1.11) and suicide risk assessment (RR: 1.31,
      95% CI: 1.21-1.42). CONCLUSIONS: Quality of care improved from 2004 to 2011 among
      patients hospitalised with schizophrenia in Denmark. DECLARATION OF INTEREST:
      None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2015. This is
      an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703721
TI  - Prevalence and correlates of explosive anger among pregnant and post-partum women
      in post-conflict Timor-Leste.
AB  - BACKGROUND: Little is known about explosive anger as a response pattern among
      pregnant and post-partum women in conflict-affected societies. AIMS: To
      investigate the prevalence and correlates of explosive anger among this
      population in Timor-Leste. METHOD: We assessed traumatic events, intimate partner
      violence, an index of adversity, explosive anger, psychological distress and post
      traumatic stress disorder among 427 women (257 in the second trimester of
      pregnancy, 170 who were 3-6 months post-partum) residing in two districts of
      Timor-Leste (response >99%). RESULTS: Two-fifths (43.6%) had explosive anger.
      Levels of functional impairment were related to frequency of explosive anger
      episodes. Explosive anger was associated with age (>35 years), being married, low
      levels of education, being employed, traumatic event count, ongoing adversity and
      intimate partner violence. CONCLUSIONS: A combination of social programmes and
      novel psychological therapies may assist in reducing severe anger among pregnant
      and post-partum women in conflict-affected countries such as Timor-Leste.
      DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2015. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703723
TI  - Excess cause-specific mortality in out-patients with personality disorder.
AB  - SUMMARY: Personality disorders (PDs) are associated with increased overall
      mortality. In patients hospitalised with a principal diagnosis of PD, this is
      observed for all clusters and for natural as well as unnatural causes of death.
      Data from Swedish nationwide registers were used to assess whether this was also
      true for the majority of patients diagnosed with PDs not severe enough to lead to
      hospitalisation. There was an increased mortality in all clusters, and for
      natural as well as unnatural death, also in patients treated as out-patients
      only, although not to the same extent as in those hospitalised. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2015.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703724
TI  - Clinical effectiveness of a skills training intervention for caregivers in
      improving patient and caregiver health following in-patient treatment for severe
      anorexia nervosa: pragmatic randomised controlled trial.
AB  - BACKGROUND: Families express a need for information to support people with severe
      anorexia nervosa. AIMS: To examine the impact of the addition of a skills
      training intervention for caregivers (Experienced Caregivers Helping Others,
      ECHO) to standard care. METHOD: Patients over the age of 12 (mean age 26 years,
      duration 72 months illness) with a primary diagnosis of anorexia nervosa and
      their caregivers were recruited from 15 in-patient services in the UK. Families
      were randomised to ECHO (a book, DVDs and five coaching sessions per caregiver)
      or treatment as usual. Patient (n=178) and caregiver (n=268) outcomes were
      measured at discharge and 6 and 12 months after discharge. RESULTS: Patients with
      caregivers in the ECHO group had reduced eating disorder psychopathology (EDE-Q)
      and improved quality of life (WHO-Quol; both effects small) and reduced in
      patient bed days (7-12 months post-discharge). Caregivers in the ECHO group had
      reduced burden (Eating Disorder Symptom Impact Scale, EDSIS), expressed emotion
      (Family Questionnaire, FQ) and time spent caregiving at 6 months but these
      effects were diminished at 12 months. CONCLUSIONS: Small but sustained
      improvements in symptoms and bed use are seen in the intervention group.
      Moreover, caregivers were less burdened and spent less time providing care.
      Caregivers had most benefit at 6 months suggesting that booster sessions, perhaps
      jointly with the patients, may be needed to maintain the effect. Sharing skills
      and information with caregivers may be an effective way to improve outcomes. This
      randomised controlled trial (RCT) was registered with Current Controlled Trials
      ISRCTN06149665. DECLARATION OF INTEREST: J.T. is a co-author of the book used in
      the ECHO intervention and receives royalties. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2015. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703725
TI  - Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in
      adults with schizophrenia: study protocol for a pilot randomised controlled
      trial.
AB  - BACKGROUND: Clozapine causes significant metabolic disturbances including obesity
      and type 2 diabetes. Recent evidence that reduced glucagon-like-peptide-1 (GLP-1)
      may contribute to aetiology of clozapine-associated metabolic dysregulation
      suggests a potential therapeutic role for GLP-1 agonists. METHOD: This open
      label, pilot randomised controlled trial evaluates the effect of exenatide in
      clozapine-treated obese adults who have schizophrenia, with or without poorly
      controlled diabetes. Sixty out-patients will be randomised to once weekly
      extended release exenatide or treatment as usual for 24 weeks. AIMS: To evaluate
      the feasibility of larger studies regarding methodology, acceptability,
      tolerability and estimate efficacy for glycaemic control or weight loss.
      Secondary outcomes are psychosis severity and metabolic parameters. CONCLUSIONS:
      This is the first trial investigating GLP-1 agonists for glycaemic control and
      weight loss in clozapine-treated patients with either diabetes or obesity.
      Clozapine-associated obesity and diabetes with exenatide (CODEX) will provide
      proof-of-concept empirical evidence addressing whether this novel treatment is
      practical and worthy of further investigation. DECLARATION OF INTEREST: A.W.R.
      has received speaker honoraria and travel grants from AstraZeneca,
      BoehringerIngelheim, Eli Lilly, MSD, Novo Nordisk and Sanofi and has participated
      on advisory panels for MSD and Novo Nordisk. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2015. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703727
TI  - The role of peri-traumatic stress and disruption distress in predicting post
      traumatic stress disorder symptoms following exposure to a natural disaster.
AB  - BACKGROUND: Few studies have examined the contribution of specific disaster
      related experiences to post-traumatic stress disorder (PTSD) symptoms. AIMS: To
      examine the roles of peri-traumatic stress and distress due to lingering disaster
      related disruption in explaining linkages between disaster exposure and PTSD
      symptoms among a cohort exposed to the 2010-2011 Canterbury (New Zealand)
      earthquakes. METHOD: Structural equation models were fitted to data obtained from
      the Christchurch Health and Development Study at age 35 (n=495), 20-24 months
      following the onset of the disaster. Measures included: earthquake exposure, peri
      traumatic stress, disruption distress and PTSD symptoms. RESULTS: The
      associations between earthquake exposure and PTSD symptoms were explained largely
      by the experience of peri-traumatic stress during the earthquakes (beta=0.189,
      P<0.0001) and disruption distress following the earthquakes (beta=0.105,
      P<0.0001). CONCLUSIONS: The results suggest the importance of minimising post
      event disruption distress following exposure to a natural disaster. DECLARATION
      OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists
      2015. This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703726
TI  - Childhood IQ and risk of bipolar disorder in adulthood: prospective birth cohort
      study.
AB  - BACKGROUND: Intellectual ability may be an endophenotypic marker for bipolar
      disorder. AIMS: Within a large birth cohort, we aimed to assess whether childhood
      IQ (including both verbal IQ (VIQ) and performance IQ (PIQ) subscales) was
      predictive of lifetime features of bipolar disorder assessed in young adulthood.
      METHOD: We used data from the Avon Longitudinal Study of Parents and Children
      (ALSPAC), a large UK birth cohort, to test for an association between measures of
      childhood IQ at age 8 years and lifetime manic features assessed at age 22-23
      years using the Hypomania Checklist-32 (HCL-32; n=1881 individuals). An ordinary
      least squares linear regression model was used, with normal childhood IQ (range
      90-109) as the referent group. We adjusted analyses for confounding factors,
      including gender, ethnicity, handedness, maternal social class at recruitment,
      maternal age, maternal history of depression and maternal education. RESULTS:
      There was a positive association between IQ at age 8 years and lifetime manic
      features at age 22-23 years (Pearson's correlation coefficient 0.159 (95% CI
      0.120-0.198), P>0.001). Individuals in the lowest decile of manic features had a
      mean full-scale IQ (FSIQ) which was almost 10 points lower than those in the
      highest decile of manic features: mean FSIQ 100.71 (95% CI 98.74-102.6) v. 110.14
      (95% CI 107.79-112.50), P>0.001. The association between IQ and manic features
      was present for FSIQ, VIQ and for PIQ but was strongest for VIQ. CONCLUSIONS: A
      higher childhood IQ score, and high VIQ in particular, may represent a marker of
      risk for the later development of bipolar disorder. This finding has implications
      for understanding of how liability to bipolar disorder may have been selected
      through generations. It will also inform future genetic studies at the interface
      of intelligence, creativity and bipolar disorder and is relevant to the
      developmental trajectory of bipolar disorder. It may also improve approaches to
      earlier detection and treatment of bipolar disorder in adolescents and young
      adults. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College
      of Psychiatrists 2015. This is an open access article distributed under the terms
      of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703728
TI  - Self-harm and suicidal acts: a suitable case for treatment of impulsivity-driven
      behaviour with repetitive transcranial magnetic stimulation (rTMS).
AB  - SUMMARY: Suicidal thinking, self-harm and suicidal acts are common, although
      determining their precise prevalence is complex. Epidemiological work has
      identified a number of associated demographic and clinical factors, though, with
      the exception of past acts of self-harm, these are non-specific and weak future
      predictors. There is a critical need shift focus from managing 'suicidality-by
      proxy' through general mental health treatments, to better understand the
      neuropsychology and neurophysiology of such behaviour to guide targeted
      interventions. The model of the cognitive control of emotion (MCCE) offers such a
      paradigm, with an underlying pan-diagnostic pathophysiology of a hypoactive
      prefrontal cortex failing to suitably inhibit an overactive threat-responding
      limbic system. The result is a phenotype - from any number of causative gene
      environment interactions - primed to impulsively self-harm. We argue that such
      neural dysconnectivity is open to potential therapeutic modification from
      repetitive transcranial magnetic stimulation (rTMS). The current evidence base
      for this is undoubtedly extremely limited, but the societal and clinical burden
      self-harm and suicide pose warrants such investigation. DECLARATION OF INTEREST:
      K.B. is the Editor of BJPsych Open, but had no editorial involvement in the
      review or decision process regarding this paper. COPYRIGHT AND USAGE: (c) The
      Royal College of Psychiatrists 2015. This is an open access article distributed
      under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC
      ND) licence.

PMID- 27703729
TI  - Psychological distress among tsunami refugees from the Great East Japan
      earthquake.
AB  - BACKGROUND: The 2011 Great Japan tsunami and nuclear leaks displaced 300 000
      people, but there are no large studies of psychological distress suffered by
      these refugees. AIMS: To provide a first assessment of major factors associated
      with distress and dysfunctional behaviour following the disasters. METHOD: All
      refugee families living in Miyagi were sent a questionnaire 10-12 months after
      the disasters. 21 981 participants (73%) returned questionnaires. Questions
      assessed psychological distress (Kessler Psychological Distress Scale, K6),
      dysfunctional behaviours, demographics, event exposure, change in physical
      activity, household visitors and emotional support. RESULTS: Nine percent scored
      13+ on the K6 indicating risk of severe mental illness. Psychological distress
      was greater among Fukushima refugees. Demographic variables, family loss, illness
      history and change in physical activity were associated with psychological
      distress and dysfunctional behaviours. Associations between psychological
      distress and dysfunction and visitors/supporters depended on relation to
      supporter. CONCLUSIONS: Practitioners need to recognise existing disease burden,
      community histories and family roles when intervening following disasters.
      DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2015. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703730
TI  - Exploring rationality in schizophrenia.
AB  - BACKGROUND: Empirical studies of rationality (syllogisms) in patients with
      schizophrenia have obtained different results. One study found that patients
      reason more logically if the syllogism is presented through an unusual content.
      AIMS: To explore syllogism-based rationality in schizophrenia. METHOD: Thirty
      eight first-admitted patients with schizophrenia and 38 healthy controls solved
      29 syllogisms that varied in presentation content (ordinary v. unusual) and
      validity (valid v. invalid). Statistical tests were made of unadjusted and
      adjusted group differences in models adjusting for intelligence and
      neuropsychological test performance. RESULTS: Controls outperformed patients on
      all syllogism types, but the difference between the two groups was only
      significant for valid syllogisms presented with unusual content. However, when
      adjusting for intelligence and neuropsychological test performance, all group
      differences became non-significant. CONCLUSIONS: When taking intelligence and
      neuropsychological performance into account, patients with schizophrenia and
      controls perform similarly on syllogism tests of rationality. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2015.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703732
TI  - Open Sesame: a new generation journal.
AB  - SUMMARY: The Royal College of Psychiatrists welcomes you to its newest peer
      reviewed research journal, British Journal of Psychiatry Open (BJPsych Open),
      which has been created to maximise the College's efforts to publish and
      disseminate the most exciting and progressive research in psychiatry and allied
      disciplines. BJPsych Open will maintain the same high quality standards
      established by the British Journal of Psychiatry (BJPsych). As an online journal
      without print restrictions, BJPsych Open will be able to publish many more
      excellent articles and article types not currently accommodated within BJPsych.
      The breadth of BJPsych Open is outlined in 'What we publish' and its strength is
      realised in our first issue, 'Powerful papers'. As editors, we welcome both your
      submissions and comments as our new generation journal grows. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2015.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703731
TI  - Serotonin transporter polymorphism (5HTTLPR), severe childhood abuse and
      depressive symptom trajectories in adulthood.
AB  - BACKGROUND: Cross-sectional studies suggest that the serotonin transporter
      promoter region polymorphism (5-HTT gene-linked polymorphic region, 5HTTLPR)
      moderates the relationship between childhood abuse and major depressive disorder.
      AIMS: To examine whether the 5HTTLPR polymorphism moderates the effect childhood
      abuse has on 5-year depressive symptom severity trajectories in adulthood.
      METHOD: At 5-year follow-up, DNA from 333 adult primary care attendees was
      obtained and genotyped for the 5HTTLPR polymorphism. Linear mixed models were
      used to test for a genotype * childhood abuse interaction effect on 5-year
      depressive symptom severity trajectories. RESULTS: After covariate adjustment,
      homozygous s allele carriers with a history of severe childhood abuse had
      significantly greater depressive symptom severity at baseline compared with those
      without a history of severe childhood abuse and this effect persisted throughout
      the 5-year period of observation. CONCLUSIONS: The 5HTTLPR s/s genotype robustly
      moderates the effects of severe childhood abuse on depressive symptom severity
      trajectories in adulthood. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE:
      (c) The Royal College of Psychiatrists 2015. This is an open access article
      distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703733
TI  - Ethical considerations in placebo-controlled randomised clinical trials.
AB  - SUMMARY: Ethical considerations in standard medical care and clinical research
      are underpinnings to quality medicine. Similarly, the placebo-controlled double
      blind randomised clinical trial is the gold standard for medical research and
      fundamental to the development of evidence-based medicine. Researchers and
      clinicians are challenged by ethical concerns in the informed consent with a need
      to maximise understanding and minimise therapeutic misconception. This editorial
      expands on themes raised by Chen et al's article 'Disclosing the Potential Impact
      of Placebo Controls in Antidepressant Trials' and serves as an invitation for
      further submissions to BJPsych Open on ethics, research design and informed
      consent. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2015. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703734
TI  - Changes in diagnosis rates and behavioural traits of autism spectrum disorder
      over time.
AB  - BACKGROUND: The increased proportion of UK children diagnosed with autism
      spectrum disorder (ASD) has been attributed to improved identification, rather
      than true increase in incidence. AIM: To explore whether the proportion of
      children with diagnosis of ASD and/or the proportion with associated behavioural
      traits had increased over a 10-year period. METHOD: A cross-cohort comparison
      using regression to compare prevalence of diagnosis and behavioural traits over
      time. Participants were children aged 7 years assessed in 1998/1999 (n=8139) and
      2007/2008 (n=13 831). RESULTS: During 1998/1999, 1.09% (95% CI 0.86-1.37) of
      children were reported as having ASD diagnosis compared with 1.68% (95% CI 1.42
      2.00) in 2007/2008: risk ratio (RR)=1.55 (95% CI 1.17-2.06), P=0.003. The
      proportion of children in the population with behavioural traits associated with
      ASD was also larger in the later cohort: RR=1.61 (95% CI 1.35-1.92), P<0.001.
      Increased odds of diagnosis at the later time point was partially accounted for
      by adjusting for the increased proportion of children with ASD-type traits.
      CONCLUSIONS: Increased ASD diagnosis may partially reflect increase in rates of
      behaviour associated with ASD and/or greater parent/teacher recognition of
      associated behaviours. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c)
      The Royal College of Psychiatrists 2015. This is an open access article
      distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703735
TI  - Question use in child mental health assessments and the challenges of listening
      to families.
AB  - BACKGROUND: The mental health assessment is a fundamental aspect of clinical
      practice and central to this is the use of questions. AIMS: To investigate the
      frequency and type of questions utilised within a child mental health assessment.
      METHOD: The data consisted of 28 naturally occurring assessments from a UK child
      and adolescent mental health service. Data were analysed using quantitative and
      qualitative content analysis to determine frequencies and question type. RESULTS:
      Results indicated a total of 9086 questions in 41 h across the 28 clinical
      encounters. This equated to a mean of 3.7 questions per minute. Four types of
      questions were identified; yes-no interrogatives, wh-prefaced questions,
      declarative questions and tag questions. CONCLUSIONS: The current format of
      questioning may impede the opportunity for families to fully express their
      particular concerns and this has implications for service delivery and training.
      DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2015. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703736
TI  - Ventral striatum dysfunction in children and adolescents with reactive attachment
      disorder: functional MRI study.
AB  - BACKGROUND: Child maltreatment is a major risk factor for psychopathology,
      including reactive attachment disorder (RAD). AIMS: To examine whether neural
      activity during reward processing was altered in children and adolescents with
      RAD. METHOD: Sixteen children and adolescents with RAD and 20 typically
      developing (TD) individuals performed tasks with high and low monetary rewards
      while undergoing functional magnetic resonance imaging. RESULTS: Significantly
      reduced activity in the caudate and nucleus accumbens was observed during the
      high monetary reward condition in the RAD group compared with the TD group
      (P=0.015, family-wise error-corrected cluster level). Significant negative
      correlations between bilateral striatal activity and avoidant attachment were
      observed in the RAD and TD groups. CONCLUSIONS: Striatal neural reward activity
      in the RAD group was markedly decreased. The present results suggest that
      dopaminergic dysfunction occurs in the striatum of children and adolescents with
      RAD, leading towards potential future risks for psychopathology. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2015.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703737
TI  - Cortical thickness and sulcal depth: insights on development and psychopathology
      in paediatric epilepsy.
AB  - BACKGROUND: The relationship between cortical thickness (CThick) and sulcal depth
      (SDepth) changes across brain regions during development. Epilepsy youth have
      CThick and SDepth abnormalities and prevalent psychiatric disorders. AIMS: This
      study compared the CThick-SDepth relationship in children with focal epilepsy
      with typically developing children (TDC) and the role played by seizure and
      psychopathology variables. METHOD: A surface-based, computational high-resolution
      three-dimesional (3D) magnetic resonance image analytic technique compared
      regional CThick-SDepth relationships in 42 participants with focal epilepsy and
      46 TDC (6-16 years) imaged in a 1.5 Tesla scanner. Psychiatric interviews
      administered to each participant yielded psychiatric diagnoses. Parents provided
      seizure-related information. RESULTS: The TDC group alone demonstrated a
      significant negative medial fronto-orbital CThick-SDepth correlation. Focal
      epilepsy participants with but not without psychiatric diagnoses showed
      significant positive pre-central and post-central CThick-SDepth associations not
      found in TDC. Although the history of prolonged seizures was significantly
      associated with the post-central CThick-SDepth correlation, it was unrelated to
      the presence/absence of psychiatric diagnoses. CONCLUSIONS: Abnormal CThick
      SDepth pre-central and post-central associations might be a psychopathology
      biomarker in paediatric focal epilepsy. DECLARATION INTEREST: None. COPYRIGHT AND
      USAGE: (c) 2015 The Royal College of Psychiatrists. This is an open access
      article distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703738
TI  - An exploration of testosterone levels in patients with bipolar disorder.
AB  - BACKGROUND: Testosterone influences well-being, mood and cognition and may play a
      role in the pathophysiology of bipolar disorder. AIM: To examine testosterone
      levels in patients with bipolar disorder compared with healthy controls. METHOD:
      We examined baseline total testosterone levels and current depression scores in
      male and female patients with bipolar disorder and mild to moderate depression
      and healthy controls. RESULTS: A significant interaction between diagnosis and
      gender was observed (F(2,97)=9.791, P=0.002). Testosterone levels were
      significantly lower for male patients with bipolar disorder compared with male
      controls (P=0.001). Women with bipolar disorder had significantly higher
      testosterone levels than female controls (P=0.03). CONCLUSIONS: Disturbances in
      testosterone levels may represent an important neurobiological abnormality in
      bipolar disorder and may differ by gender. If these findings are confirmed, the
      use of gender appropriate treatment strategies for the normalisation of
      testosterone levels in bipolar disorder depression should be further explored.
      DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2015. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703739
TI  - Alterations in dorsal and ventral posterior cingulate connectivity in APOE
      epsilon4 carriers at risk of Alzheimer's disease.
AB  - BACKGROUND: Recent evidence suggests that exercise plays a role in cognition and
      that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral
      subregions based on distinct connectivity patterns. AIMS: To examine the effect
      of physical activity and division of the PCC on brain functional connectivity
      measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of
      apolipoprotein E (APOE epsilon4) allele. METHOD: Participants were 22 SMC
      carrying the APOE epsilon4 allele (epsilon4+; mean age 72.18 years) and 58 SMC
      non-carriers (epsilon4-; mean age 72.79 years). Connectivity of four dorsal and
      ventral seeds was examined. Relationships between PCC connectivity and physical
      activity measures were explored. RESULTS: epsilon4+ individuals showed increased
      connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the
      ventral PCC and supplementary motor area (SMA). Greater levels of physical
      activity correlated with the magnitude of ventral PCC-SMA connectivity.
      CONCLUSIONS: The results provide the first evidence that epsilon4+ individuals at
      increased risk of cognitive decline show distinct alterations in dorsal and
      ventral PCC functional connectivity. DECLARATION OF INTEREST: D.A. has served on
      scientific advisory boards for Novartis, Eli Lilly, Janssen, Prana and Pfizer,
      and as Editor-in-Chief for International Psychogeriatrics; received speaker
      honoraria from Pfizer and Lundbeck, and research support from Eli Lilly,
      GlaxoSmithKline, Forest Laboratories, Novartis, and CSIRO. C.L.M. has received
      consulting fees from Eli Lilly and Prana Biotechnology, and has stock ownership
      in Prana Biotechnology. C.C.R. has received consultancy payments from Roche and
      Piramal, and research support from Avid Radiopharmaceuticals, Eli Lilly, GE
      Healthcare, Piramal and Navidea for amyloid imaging. C.S. has provided clinical
      consultancy and been on scientific advisory committees for the Australian CSIRO,
      Alzheimer's Australia, University of Melbourne and other relationships, which are
      subject to confidentiality clauses; she has been a named Chief Investigator on
      investigator-driven collaborative research projects in partnership with Pfizer,
      Merck, Piramal, Bayer and GE Healthcare. Her research programme has received
      support from the National Health and Medical Research Council Alzheimer's
      Association, Collier Trust, Scobie and Claire McKinnon Foundation, JO and JR
      Wicking Trust, Shepherd Foundation, Brain Foundation, Mason Foundation,
      Ramaciotti Foundation, Alzheimer's Australia and the Royal Australian College of
      Physicians. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2015.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703740
TI  - Treatment of psychosis in prisons and violent recidivism.
AB  - BACKGROUND: Violence among released prisoners with psychosis is an important
      public health problem. It is unclear whether treatment in prison can influence
      criminal behaviour subsequent to release. AIMS: To investigate whether treatment
      in prison can delay time to reoffending. METHOD: Our sample consisted of 1717
      adult prisoners in England and Wales convicted of a serious violent or sexual
      offence. We used Cox regression to investigate the effects of treatment received
      in prison on associations between mental illness and time to first reconviction
      following release. RESULTS: Prisoners with current symptoms of schizophrenia
      reoffended quicker following release. Nevertheless, treatment with medication
      significantly delayed time to violence (18% reduction). Treatment for substance
      dependence delayed violent and non-violent reoffending among prisoners with drug
      induced psychosis. CONCLUSIONS: Identifying prisoners with psychosis and
      administering treatment in prison have important protective effects against
      reoffending. Repeated screening with improved accuracy in identification is
      necessary to prevent cases being missed. DECLARATION OF INTEREST: None. COPYRIGHT
      AND USAGE: (c) The Royal College of Psychiatrists 2015. This is an open access
      article distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703741
TI  - Psychiatric intervention and repeated admission to emergency centres due to drug
      overdose.
AB  - BACKGROUND: Repeated drug overdose is a major risk factor for suicide. Data are
      lacking on the effect of psychiatric intervention on preventing repeated drug
      overdose. AIMS: To investigate whether psychiatric intervention was associated
      with reduced readmission to emergency centres due to drug overdose. METHOD: Using
      a Japanese national in-patient database, we identified patients who were first
      admitted to emergency centres for drug overdose in 2010-2012. We used propensity
      score matching for patient and hospital factors to compare readmission rates
      between intervention (patients undergoing psychosocial assessment) and unexposed
      groups. RESULTS: Of 29 564 eligible patients, 13 035 underwent psychiatric
      intervention. In the propensity-matched 7938 pairs, 1304 patients were readmitted
      because of drug overdose. Readmission rate was lower in the intervention than in
      the unexposed group (7.3% v. 9.1% respectively, P<0.001). CONCLUSIONS:
      Psychiatric intervention was associated with reduced readmission in patients who
      had taken a drug overdose. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE:
      (c) The Royal College of Psychiatrists 2015. This is an open access article
      distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703742
TI  - Effect of the First World War on suicide rates in Ireland: an investigation of
      the 1864-1921 suicide trends.
AB  - SUMMARY: Since the proposition of the social integration theory by Emile
      Durkheim, macro-sociological changes have been speculated to affect suicide
      rates. This study investigates the effect of the First World War on Irish suicide
      rates. We applied an interrupted time series design of 1864-1921 annual Irish
      suicide rates. The 1864-1913 suicide rates exhibited a slow-rising trend with a
      sharp decline from the year 1914 onwards. The odds for death by suicide for males
      during the 1914-1918 period was 0.811 (95% CI 0.768-0.963). Irish rates of
      suicide were significantly reduced during the First World War, most notably for
      males. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) 2015 The Royal
      College of Psychiatrists. This is an open access article distributed under the
      terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703743
TI  - Paediatric bipolar disorder: international comparisons of hospital discharge
      rates 2000-2010.
AB  - BACKGROUND: Controversy surrounds the diagnosis and prevalence of paediatric
      bipolar disorder, with estimates varying considerably between countries. AIMS: To
      determine the international hospital discharge rates for paediatric bipolar
      disorder compared with all other psychiatric diagnoses. METHOD: We used national
      data-sets from 2000 to 2010 from England, Australia, New Zealand, the USA and
      Germany. RESULTS: For those aged under 20 years, the discharge rates for
      paediatric bipolar disorder per 100 000 population were: USA 95.6, Australia
      11.7, New Zealand 6.3, Germany 1.5 and England 0.9. The most marked divergence in
      discharge rates was in 5- to 9-year-olds: USA 27, New Zealand 0.22, Australia
      0.14, Germany 0.03 and England 0.00. CONCLUSIONS: The disparity between US and
      other discharge rates for paediatric bipolar disorder is markedly greater than
      the variation for child psychiatric discharge rates overall, and for adult rates
      of bipolar disorder. This suggests there may be differing diagnostic practices
      for paediatric bipolar disorder in the USA. DECLARATION OF INTEREST: None.
      COPYRIGHT AND USAGE: (c) 2015 The Royal College of Psychiatrists. This is an open
      access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703745
TI  - High heterogeneity and low reliability in the diagnosis of major depression will
      impair the development of new drugs.
AB  - SUMMARY: Major depressive disorder is a common diagnosis associated with a high
      burden of disease that has proven to be highly heterogeneous and unreliable.
      Treatments currently available demonstrate limited efficacy and effectiveness.
      New drug development is urgently required but is likely to be hindered by
      diagnostic limitations. DECLARATIONS OF INTEREST: D.J.C. has received grants and
      personal fees from Eli Lilly, Janssen-Cilag, Roche, Allergen, Bristol-Myers
      Squibb, Pfizer, Lundbeck, AstraZeneca, Hospira, Organon, Sanofi-Aventis, and
      Wyeth during the writing of this review. C.P. has received grant support from
      Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, and received honoraria
      for consultancy to Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca,
      Pfizer, Schering Plough, and Lundbeck. Over the past 2 years he has participated
      on advisory boards for Janssen-Cilag and Lundbeck, and received honoraria for
      talks presented at educational meetings organised by AstraZeneca, Janssen-Cilag
      and Lundbeck. M.H. has received personal fees or grants from Lundbeck,
      AstraZeneca and Servier during the writing of this review. A.H.Y. reports
      personal fees from Lundbeck, Sunovion, AstraZeneca and Janssen outside the
      submitted work. I.P.E. has received personal fees or grants from Lundbeck,
      AstraZeneca, and Abbvie during the writing of this review. COPYRIGHT AND USAGE:
      (c) The Royal College of Psychiatrists 2015. This is an open access article
      distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703746
TI  - Psychiatric hospital treatment of children and adolescents in New South Wales,
      Australia: 12-year trends.
AB  - BACKGROUND: It is preferable that children and adolescents requiring in-patient
      care for mental health problems are managed in age-appropriate facilities. To
      achieve this, nine specialist Child and Adolescent Mental Health Services (CAMHS)
      in-patient units have been commissioned in New South Wales (NSW) since 2002.
      AIMS: To examine trends in child and adolescent in-patient admissions since the
      opening of these CAMHS units. METHOD: Analysis of separation data for under 18
      year-olds to CAMHS, adult mental health and paediatric units for the period 2002
      to 2013 in NSW, comparing districts with and without specialist CAMHS units.
      RESULTS: Separations from CAMHS, adult and paediatric units rose with time, but
      there was no interaction between time and health district type (with/without
      CAMHS unit). Five of eight health districts experienced increased separations of
      under 18-year-olds from adult units in the year of opening a CAMHS unit.
      Separations from related paediatric units increased in three of seven health
      districts. CONCLUSIONS: Opening CAMHS units may be followed by a temporary
      increase in separations of young people from adult units, but it does not
      influence the flow of patients to non-CAMHS facilities in the longer term.
      DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2016. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703744
TI  - Adjunctive aripiprazole in risperidone-induced hyperprolactinaemia: double-blind,
      randomised, placebo-controlled trial.
AB  - BACKGROUND: Hyperprolactinaemia is a troublesome side-effect of treatment with
      antipsychotics. AIMS: This double-blind, placebo-controlled study aimed at
      examining the effect of adjunctive treatment with 10 mg aripiprazole on prolactin
      levels and sexual side-effects in patients with schizophrenia symptomatically
      maintained on risperidone. METHOD: Thirty patients taking risperidone were
      enrolled into the trial (CTRI/2012/11/003114). Aripiprazole was administered at a
      fixed daily dose of 10 mg/day for 8 weeks. Serum prolactin was measured at
      baseline and at 8 weeks. Hyperprolactinaemia-related problems, psychopathology
      and side-effects were evaluated every 2 weeks. RESULTS: Prolactin levels
      decreased by 58% in the aripiprazole group compared with an increase by 22% in
      the placebo group. Prolactin levels normalised in 46% of patients in the
      aripiprazole group (number needed to treat, NNT=2). Aripiprazole improved
      erectile dysfunction in five out of six patients. There were no significant
      differences in change in psychopathology or side-effects between groups.
      CONCLUSIONS: Adjunctive aripiprazole reduced prolactin levels in those treated
      with risperidone, with no effect on psychopathology and extrapyramidal symptoms.
      This is a potential treatment for hyperprolactinaemia observed during treatment
      with second-generation antipsychotics. DECLARATION OF INTEREST: None. COPYRIGHT
      AND USAGE: (c) The Royal College of Psychiatrists 2015. This is an open access
      article distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703747
TI  - Origin and schizophrenia in young refugees and inter-country adoptees from Latin
      America and East Africa in Sweden: a comparative study.
AB  - BACKGROUND: Migrants' socioeconomic adversity has been linked to schizophrenia.
      AIMS: To investigate whether the more favourable socioeconomic situation of
      adoptees prevents them from the high risk of schizophrenia found in other
      migrants. METHOD: Register study in a cohort of refugees and inter-country
      adoptees aged 16-40 years, born in East Africa (n=8389), Latin America (n=11 572)
      and 1.2 million native Swedes. Cox-regression models estimated hazard ratios
      (HRs) of schizophrenia in data from psychiatric care. RESULTS: Despite diverse
      income levels, HRs for schizophrenia were similar for refugees and adoptees, with
      East Africans having the highest HRs: 5.83 (3.30-10.27) and 5.80 (5.03-6.70),
      followed by Latin Americans: HRs 3.09 (2.49-3.83) and 2.31 (1.79-2.97), compared
      with native Swedes. Adjustment for income decreased these risks slightly for
      refugees, but not for adoptees. CONCLUSIONS: This study suggests that risk
      factors associated with origin are more important determinants of schizophrenia
      than socioeconomic adversity in the country of settlement. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) 2016 The Royal College of Psychiatrists.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703748
TI  - Hospital treatment, mortality and healthcare costs in relation to socioeconomic
      status among people with bipolar affective disorder.
AB  - BACKGROUND: Evidence regarding the relationships between the socioeconomic status
      and long-term outcomes of individuals with bipolar affective disorder (BPD) is
      lacking. AIMS: We aimed to estimate the effects of baseline socioeconomic status
      on longitudinal outcomes. METHOD: A national cohort of adult participants with
      newly diagnosed BPD was identified in 2008. The effects of personal and household
      socioeconomic status were explored on outcomes of hospital treatment, mortality
      and healthcare costs, over a 3-year follow-up period (2008-2011). RESULTS: A
      total of 7987 participants were recruited. The relative risks of hospital
      treatment and mortality were found elevated for the ones from low-income
      households who also had higher healthcare costs. Low premium levels did not
      correlate with future healthcare costs. CONCLUSIONS: Socioeconomic deprivation is
      associated with poorer outcome and higher healthcare costs in BPD patients.
      Special care should be given to those with lower socioeconomic status to improve
      outcomes with potential benefits of cost savings in the following years.
      DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) 2016 The Royal College of
      Psychiatrists. This is an open access article distributed under the terms of the
      Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703749
TI  - Claims for sickness and disability benefits owing to mental disorders in the UK:
      trends from 1995 to 2014.
AB  - BACKGROUND: There is international concern about the levels of sickness and
      disability benefits, with mental disorders known to account for a large
      proportion of claims. AIMS: To examine trends in sickness and disability benefits
      awarded for mental disorders in the UK. METHOD: The researchers analysed UK
      Government data from 1995 to 2014. RESULTS: Mental disorders have become the most
      common cause of receiving benefits, with the number of claimants rising by 103%
      from 1995 to 1.1 million in 2014. Claimants with other conditions fell by 35%. In
      2014, 47% of claims were attributed to a mental disorder. The number of long-term
      claimants (claiming over 5 years) with mental disorders increased by 87% from
      2000 to 2011. Two-thirds of mental disorder claimants were classified as having a
      depressive or anxiety disorder. CONCLUSIONS: Common mental disorders may involve
      greater morbidity and social costs than usually recognised. Availability of
      suitable employment, as well as individual support, may be necessary to reduce
      benefit levels. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2016. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703750
TI  - The challenges of implementing ADHD clinical guidelines and research best
      evidence in routine clinical care settings: Delphi survey and mixed-methods
      study.
AB  - BACKGROUND: The landmark US Multimodal Treatment of ADHD (MTA) study established
      the benefits of individualised medication titration and optimisation strategies
      to improve short- to medium-term outcomes in attention-deficit hyperactivity
      disorder (ADHD). This individualised medication management approach was
      subsequently incorporated into the National Institute for Health and Care
      Excellence (NICE) ADHD Clinical Guidelines (NICE CG78). However, little is known
      about clinicians' attitudes towards implementing these medication management
      strategies for ADHD in routine care. AIMS: To examine National Health Service
      (NHS) healthcare professionals' consensus on ADHD medication management
      strategies. METHOD: Using the Delphi method, we examined perceptions on the
      importance and feasibility of implementing 103 ADHD treatment statements from
      sources including the UK NICE ADHD guidelines and US medication management
      algorithms. RESULTS: Certain recommendations for ADHD medication management were
      judged as important and feasible to implement, including a stepwise titration of
      stimulant medication. Other recommendations were perceived as important but not
      feasible to implement in routine practice, such as weekly clinic follow-up with
      the family during titration and collection of follow-up symptom questionnaires.
      CONCLUSIONS: Many of the key guideline recommendations for ADHD medication
      management are viewed by clinicians as important and feasible to implement.
      However, some recommendations present significant implementation challenges
      within the context of routine NHS clinical care in England. DECLARATION OF
      INTEREST: C.H. and K.S. were members of the Guideline Development Group for the
      NICE ADHD Clinical Guideline (NICE CG78). COPYRIGHT AND USAGE: (c) 2016 The Royal
      College of Psychiatrists. This is an open access article distributed under the
      terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703751
TI  - The long-term mental health impact of peacekeeping: prevalence and predictors of
      psychiatric disorder.
AB  - BACKGROUND: The mental health outcomes of military personnel deployed on
      peacekeeping missions have been relatively neglected in the military mental
      health literature. AIMS: To assess the mental health impacts of peacekeeping
      deployments. METHOD: In total, 1025 Australian peacekeepers were assessed for
      current and lifetime psychiatric diagnoses, service history and exposure to
      potentially traumatic events (PTEs). A matched Australian community sample was
      used as a comparator. Univariate and regression analyses were conducted to
      explore predictors of psychiatric diagnosis. RESULTS: Peacekeepers had
      significantly higher 12-month prevalence of post-traumatic stress disorder
      (16.8%), major depressive episode (7%), generalised anxiety disorder (4.7%),
      alcohol misuse (12%), alcohol dependence (11.3%) and suicidal ideation (10.7%)
      when compared with the civilian comparator. The presence of these psychiatric
      disorders was most strongly and consistently associated with exposure to PTEs.
      CONCLUSIONS: Veteran peacekeepers had significant levels of psychiatric
      morbidity. Their needs, alongside those of combat veterans, should be recognised
      within military mental health initiatives. DECLARATION OF INTEREST: None.
      COPYRIGHT AND USAGE: This is an open access article distributed under the terms
      of the Creative Commons Attribution (CC BY) licence.

PMID- 27703753
TI  - The Problem Behaviour Checklist: short scale to assess challenging behaviours.
AB  - BACKGROUND: Challenging behaviour, especially in intellectual disability, covers
      a wide range that is in need of further evaluation. AIMS: To develop a short but
      comprehensive instrument for all aspects of challenging behaviour. METHOD: In the
      first part of a two-stage enquiry, a 28-item scale was constructed to examine the
      components of challenging behaviour. Following a simple factor analysis this was
      developed further to create a new short scale, the Problem Behaviour Checklist
      (PBCL). The scale was subsequently used in a randomised controlled trial and
      tested for interrater reliability. Scores were also compared with a standard
      scale, the Modified Overt Aggression Scale (MOAS). RESULTS: Seven identified
      factors - personal violence, violence against property, self-harm, sexually
      inappropriate, contrary, demanding and disappearing behaviour - were scored on a
      5-point scale. A subsequent factor analysis with the second population showed
      demanding, violent and contrary behaviour to account for most of the variance.
      Interrater reliability using weighted kappa showed good agreement (0.91; 95% CI
      0.83-0.99). Good agreement was also shown with scores on the MOAS and a score of
      1 on the PBCL showed high sensitivity (97%) and specificity (85%) for a threshold
      MOASscore of 4. CONCLUSIONS: The PBCL appears to be a suitable and practical
      scale for assessing all aspects of challenging behaviour. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) 2016 The Royal College of Psychiatrists.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703752
TI  - Low birth weight and features of neuroticism and mood disorder in 83 545
      participants of the UK Biobank cohort.
AB  - BACKGROUND: Low birth weight has been inconsistently associated with risk of
      developing affective disorders, including major depressive disorder (MDD). To
      date, studies investigating possible associations between birth weight and
      bipolar disorder (BD), or personality traits known to predispose to affective
      disorders such as neuroticism, have not been conducted in large cohorts. AIMS: To
      assess whether very low birth weight (<1500 g) and low birth weight (1500-2490 g)
      were associated with higher neuroticism scores assessed in middle age, and
      lifetime history of either MDD or BD. We controlled for possible confounding
      factors. METHOD: Retrospective cohort study using baseline data on the 83 545 UK
      Biobank participants with detailed mental health and birth weight data. Main
      outcomes were prevalent MDD and BD, and neuroticism assessed using the Eysenck
      Personality Inventory Neuroticism scale - Revised (EPIN-R). RESULTS: Referent to
      normal birth weight, very low/low birth weight were associated with higher
      neuroticism scores, increased MDD and BD. The associations between birth weight
      category and MDD were partially mediated by higher neuroticism. CONCLUSIONS:
      These findings suggest that intrauterine programming may play a role in lifetime
      vulnerability to affective disorders. DECLARATION OF INTEREST: None. COPYRIGHT
      AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open access
      article distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703754
TI  - Treating anxiety and depression in older adults: randomised controlled trial
      comparing guided v. self-guided internet-delivered cognitive-behavioural therapy.
AB  - BACKGROUND: Symptoms of anxiety and depression are prevalent in older adults.
      AIMS: To compare clinician-guided and self-guided versions of a transdiagnostic
      internet-delivered cognitive-behavioural therapy (iCBT) intervention for adults
      aged 60 years and above. METHOD: Adults (n=433) with symptoms of anxiety and
      depression were randomly allocated to: (1) clinician-guided treatment (n=153);
      (2) initial clinician interview followed by self-guided treatment (n=140); or (3)
      self-guided treatment without interview (n=140). RESULTS: Large reductions (d
      >=1.00) in symptoms of depression and anxiety were observed across groups, and
      sustained at follow-up. No differences were observed in clinical outcomes or
      satisfaction ratings. Age did not affect outcomes. CONCLUSIONS: Carefully
      developed iCBT interventions may significantly reduce symptoms of anxiety and
      depression in older adults when delivered in either clinician-guided or self
      guided formats. DECLARATION OF INTEREST: N.T. and B.F.D. developed the Wellbeing
      Plus Course but derive no financial benefit from it. COPYRIGHT AND USAGE: (c)
      2016 The Royal College of Psychiatrists. This is an open access article
      distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703755
TI  - Long-term antipsychotic treatment in schizophrenia: systematic review and network
      meta-analysis of randomised controlled trials.
AB  - BACKGROUND: For treatment of patients diagnosed with schizophrenia, comparative
      long-term effectiveness of antipsychotic drugs to reduce relapses when minimising
      adverse effects is of clinical interest, hence prompting this review. AIMS: To
      evaluate the comparative long-term effectiveness of antipsychotic drugs. METHOD:
      We systematically searched electronic databases for reports of randomised
      controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing relapse
      risks in schizophrenia. We conducted network meta-analysis of 18 antipsychotics
      and placebo. RESULTS: Studies of 10 177 patients in 56 reports were included;
      treatment duration averaged 48 weeks (range 4-156). Olanzapine was significantly
      more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI 0.14-0.88) or
      haloperidol (OR=0.50, 95% CI 0.30-0.82); and fluphenazine decanoate was more
      effective than chlorpromazine (OR=0.31, 95% CI 0.11-0.88) in relapse reduction.
      Fluphenazine decanoate, haloperidol, haloperidol decanoate and trifluoperazine
      produced more extrapyramidal adverse effects than olanzapine or quetiapine; and
      olanzapine was associated with more weight gain than other agents. CONCLUSIONS:
      Except for apparent superiority of olanzapine and fluphenazine decanoate over
      chlorpromazine, most agents showed intermediate efficacy for relapse prevention
      and differences among them were minor. Typical antipsychotics yielded adverse
      neurological effects, and olanzapine was associated with weight gain. The
      findings may contribute to evidence-based treatment selection for patients with
      chronic psychotic disorders. DECLARATION OF INTEREST: R.J.B. received grants from
      the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology
      Research Fund. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703756
TI  - Online screening and feedback to increase help-seeking for mental health
      problems: population-based randomised controlled trial.
AB  - BACKGROUND: Community-based screening for mental health problems may increase
      service use through feedback to individuals about their severity of symptoms and
      provision of contacts for appropriate services. AIMS: The effect of symptom
      feedback on service use was assessed. Secondary outcomes included symptom change
      and study attrition. METHOD: Using online recruitment, 2773 participants
      completed a comprehensive survey including screening for depression (n=1366) or
      social anxiety (n=1407). Across these two versions, approximately half (n=1342)
      of the participants were then randomly allocated to receive tailored feedback.
      Participants were reassessed after 3 months (Australian New Zealand Clinical
      Trials Registry ANZCTR12614000324617). RESULTS: A negative effect of providing
      social anxiety feedback to individuals was observed, with significant reductions
      in professional service use. Greater attrition and lower intentions to seek help
      were also observed after feedback. CONCLUSIONS: Online mental health screening
      with feedback is not effective for promoting professional service use.
      Alternative models of online screening require further investigation. DECLARATION
      OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists
      2016. This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703757
TI  - Embodying self-compassion within virtual reality and its effects on patients with
      depression.
AB  - BACKGROUND: Self-criticism is a ubiquitous feature of psychopathology and can be
      combatted by increasing levels of self-compassion. However, some patients are
      resistant to self-compassion. AIMS: To investigate whether the effects of self
      identification with virtual bodies within immersive virtual reality could be
      exploited to increase self-compassion in patients with depression. METHOD: We
      developed an 8-minute scenario in which 15 patients practised delivering
      compassion in one virtual body and then experienced receiving it from themselves
      in another virtual body. RESULTS: In an open trial, three repetitions of this
      scenario led to significant reductions in depression severity and self-criticism,
      as well as to a significant increase in self-compassion, from baseline to 4-week
      follow-up. Four patients showed clinically significant improvement. CONCLUSIONS:
      The results indicate that interventions using immersive virtual reality may have
      considerable clinical potential and that further development of these methods
      preparatory to a controlled trial is now warranted. DECLARATION OF INTEREST:
      None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is
      an open access article distributed under the terms of the Creative Commons
      Attribution (CC BY) licence.

PMID- 27703758
TI  - Protocol investigating the clinical outcomes and cost-effectiveness of cognitive
      behavioural therapy delivered remotely for unscheduled care users with health
      anxiety: randomised controlled trial.
AB  - BACKGROUND: Health anxiety and medically unexplained symptoms cost the National
      Health Service (NHS) an estimated L3 billion per year in unnecessary costs with
      little evidence of patient benefit. Effective treatment is rarely taken up due to
      issues such as stigma or previous negative experiences with mental health
      services. An approach to overcome this might be to offer remotely delivered
      psychological therapy, which can be just as effective as face-to-face therapy and
      may be more accessible and suitable. AIMS: To investigate the clinical outcomes
      and cost-effectiveness of remotely delivered cognitive-behavioural therapy (CBT)
      to people with high health anxiety repeatedly accessing unscheduled care (trial
      registration: NCT02298036). METHOD: A multicentre randomised controlled trial
      (RCT) will be undertaken in primary and secondary care providers of unscheduled
      care across the East Midlands. One hundred and forty-four eligible participants
      will be equally randomised to receive either remote CBT (6-12 sessions) or
      treatment as usual (TAU). Two doctoral research studies will investigate the
      barriers and facilitators to delivering the intervention and the factors
      contributing to the optimisation of therapeutic outcome. RESULTS: This trial will
      be the first to test the clinical outcomes and cost-effectiveness of remotely
      delivered CBT for the treatment of high health anxiety. CONCLUSIONS: The findings
      will enable an understanding as to how this intervention might fit into a wider
      care pathway to enhance patient experience of care. DECLARATION OF INTEREST:
      None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is
      an open access article distributed under the terms of the Creative Commons Non
      commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703759
TI  - Auditory verbal hallucinations in first-episode psychosis: a phenomenological
      investigation.
AB  - BACKGROUND: In dimensional understanding of psychosis, auditory verbal
      hallucinations (AVH) are unitary phenomena present on a continuum from non
      clinical voice hearing to severe mental illness. There is mixed evidence for this
      approach and a relative absence of research into subjective experience of AVH in
      early psychosis. AIMS: To conduct primary research into the nature of subjective
      experience of AVH in first-episode psychosis. METHOD: A phenomenological study
      using diary and photo-elicitation qualitative techniques investigating the
      subjective experience of AVH in 25 young people with first-episode psychosis.
      RESULTS: AVH are characterised by: (a) entity, as though from a living being with
      complex social interchange; and (b) control, exerting authority with ability to
      influence. AVH are also received with passivity, often accompanied by sensation
      in other modalities. CONCLUSIONS: A modern detailed phenomenological
      investigation, without presupposition, gives results that echo known descriptive
      psychopathology. However, novel findings also emerge that may be features of AVH
      in psychosis not currently captured with standardised measures. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703760
TI  - Predicting hospital aggression in secure psychiatric care.
AB  - BACKGROUND: Risk assessment instruments have become a preferred means for
      predicting future aggression, claiming to predict long-term aggression risk.
      AIMS: To investigate the predictive value over 12 months and 4 years of two
      commonly applied instruments (Historical, Clinical and Risk Management - 20 (HCR
      20) and Violence Risk Appraisal Guide (VRAG)). METHOD: Participants were adult
      male psychiatric patients detained in a high secure hospital. All had a diagnosis
      of personality disorder. The focus was on aggression in hospital. RESULTS: The
      actuarial risk assessment (VRAG) was generally performing better than the
      structured risk assessment (HCR-20), although neither approach performed
      particularly well overall. Any value in their predictive potential appeared
      focused on the longer time period under study (4 years) and was specific to
      certain types of aggression. CONCLUSIONS: The value of these instruments for
      assessing aggression in hospital among patients with personality disorder in a
      high secure psychiatric setting is considered. DECLARATION OF INTEREST: J.L.I.,
      C.A.M. and J.K. are employed by the trust where the data were collected.
      COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open
      access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703761
TI  - Is it time to abandon suicide risk assessment?
AB  - SUMMARY: Suicide risk assessment includes estimating the likelihood of suicide in
      words such as 'low, medium or high'. A 'high suicide risk' rating can trigger a
      powerful urge to eliminate risk immediately. But it is far from clear what 'high
      suicide risk' actually means. In the current state of knowledge, suicide
      reduction measures should apply to all psychiatric patients, irrespective of an
      individual patient's perceived risk. For patients presenting with suicidal
      thoughts, feelings and behaviour, assessment and management should focus on
      reducing or tolerating emotional pain. DECLARATION OF INTEREST: D.M. has received
      payments from Janssen-Cilag and Servier. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2016. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703762
TI  - Patient characteristics as a moderator of post-traumatic stress disorder
      treatment outcome: combining symptom burden and strengths.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) psychotherapy research has
      failed to identify patient characteristics that consistently predict differential
      outcome. AIMS: To identify patient characteristics associated with differential
      outcome via a statistically generated composite moderator among women with
      childhood abuse-related PTSD in a randomised controlled trial comparing exposure
      therapy, skills training and their combination. METHOD: Six baseline patient
      characteristics were combined in a composite moderator of treatment effects for
      PTSD symptoms across the three treatment conditions through a 6-month follow-up.
      RESULTS: The optimal moderator was the combined burden of all symptoms and
      emotion regulation strength. Those with high moderator scores, reflecting high
      symptom load relative to emotion regulation, did least well in exposure,
      moderately well in skills and best in the combination. CONCLUSIONS: A clinically
      meaningful moderator, which combines patient symptom burden and strengths, was
      identified. Assessment at follow-up may provide a more accurate indicator of
      variability in outcome than that obtained immediately post-treatment. DECLARATION
      OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists
      2016. This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703763
TI  - 1-year follow-up of neurofeedback treatment in adolescents with attention-deficit
      hyperactivity disorder: randomised controlled trial.
AB  - BACKGROUND: Estimates of the effectiveness of neurofeedback as a treatment for
      attention-deficit hyperactivity disorder (ADHD) are mixed. AIMS: To investigate
      the long-term additional effects of neurofeedback (NFB) compared with treatment
      as usual (TAU) for adolescents with ADHD. METHOD: Using a multicentre parallel
      randomised controlled trial design, 60 adolescents with a DSM-IV-TR diagnosis of
      ADHD receiving NFB+TAU (n=41) or TAU (n=19) were followed up. Neurofeedback
      treatment consisted of approximately 37 sessions of theta/sensorimotor rhythm
      (SMR)-training on the vertex (Cz). Outcome measures included behavioural self
      reports and neurocognitive measures. Allocation to the conditions was unmasked.
      RESULTS: At 1-year follow-up, inattention as reported by adolescents was
      decreased (range etap2=0.23-0.36, P<0.01) and performance on neurocognitive tasks
      was faster (range etap2=0.20-0.67, P<0.005) irrespective of treatment group.
      CONCLUSIONS: Overall, NFB+TAU was as effective as TAU. Given the absence of
      robust additional effects of neurofeedback in the current study, results do not
      support the use of theta/SMR neurofeedback as a treatment for adolescents with
      ADHD and comorbid disorders in clinical practice. DECLARATION OF INTEREST: None.
      COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open
      access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703764
TI  - Light therapy for non-seasonal depression: systematic review and meta-analysis.
AB  - BACKGROUND: Light therapy is a known treatment for patients with seasonal
      affective disorder. However, the efficacy of light therapy in treating patients
      with non-seasonal depression remains inconclusive. AIMS: To provide the current
      state of evidence for efficacy of light therapy in non-seasonal depressive
      disorders. METHOD: Systematic review of randomised controlled trials (RCTs) was
      conducted by searching MEDLINE, EMBASE, PsycINFO, CINAHL, and CENTRAL from their
      inception to September 2015. Study selection, data abstraction and risk of bias
      assessment were independently conducted in duplicate. Meta-analyses were
      performed to provide a summary statistic for the included RCTs. The reporting of
      this systematic review follows the PRISMA guidelines. RESULTS: A meta-analysis
      including 881 participants from 20 RCTs demonstrated a beneficial effect of light
      therapy in non-seasonal depression (standardised mean difference in depression
      score -0.41 (95% CI -0.64 to -0.18)). This estimate was associated with
      significant heterogeneity (I2=60%, P=0.0003) that was not sufficiently explained
      by subgroup analyses. There was also high risk of bias in the included trials
      limiting the study interpretation. CONCLUSIONS: The overall quality of evidence
      is poor due to high risk of bias and inconsistency. However, considering that
      light therapy has minimal side-effects and our meta-analysis demonstrated that a
      significant proportion of patients achieved a clinically significant response,
      light therapy may be effective for patients with non-seasonal depression and can
      be a helpful additional therapeutic intervention for depression. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703765
TI  - Case finding and screening clinical utility of the Patient Health Questionnaire
      (PHQ-9 and PHQ-2) for depression in primary care: a diagnostic meta-analysis of
      40 studies.
AB  - BACKGROUND: The Patient Health Questionnaire (PHQ) is the most commonly used
      measure to screen for depression in primary care but there is still lack of
      clarity about its accuracy and optimal scoring method. AIMS: To determine via
      meta-analysis the diagnostic accuracy of the PHQ-9-linear, PHQ-9-algorithm and
      PHQ-2 questions to detect major depressive disorder (MDD) among adults. METHOD:
      We systematically searched major electronic databases from inception until June
      2015. Articles were included that reported the accuracy of PHQ-9 or PHQ-2
      questions for diagnosing MDD in primary care defined according to standard
      classification systems. We carried out a meta-analysis, meta-regression,
      moderator and sensitivity analysis. RESULTS: Overall, 26 publications reporting
      on 40 individual studies were included representing 26 902 people (median 502,
      s.d.=693.7) including 14 760 unique adults of whom 14.3% had MDD. The
      methodological quality of the included articles was acceptable. The meta-analytic
      area under the receiver operating characteristic curve of the PHQ-9-linear and
      the PHQ-2 was significantly higher than the PHQ-9-algorithm, a difference that
      was maintained in head-to-head meta-analysis of studies. Our best estimates of
      sensitivity and specificity were 81.3% (95% CI 71.6-89.3) and 85.3% (95% CI 81.0
      89.1), 56.8% (95% CI 41.2-71.8) and 93.3% (95% CI 87.5-97.3) and 89.3% (95% CI
      81.5-95.1) and 75.9% (95% CI 70.1-81.3) for the PHQ-9-linear, PHQ-9-algorithm and
      PHQ-2 respectively. For case finding (ruling in a diagnosis), none of the methods
      were suitable but for screening (ruling out non-cases), all methods were
      encouraging with good clinical utility, although the cut-off threshold must be
      carefully chosen. CONCLUSIONS: The PHQ can be used as an initial first step
      assessment in primary care and the PHQ-2 is adequate for this purpose with good
      acceptability. However, neither the PHQ-2 nor the PHQ-9 can be used to confirm a
      clinical diagnosis (case finding). DECLARATION OF INTEREST: None. COPYRIGHT AND
      USAGE: (c) The Royal College of Psychiatrists 2016. This is an open access
      article distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703766
TI  - The effect of second-generation antipsychotics on hippocampal volume in first
      episode of psychosis: longitudinal study.
AB  - BACKGROUND: Current neuroscience literature has related treatment with
      aripiprazole to improved memory performance and subcellular changes in the
      hippocampus. AIMS: To explore the volumetric changes in hippocampal grey matter
      in people with a first episode of psychosis (FEP) treated with second-generation
      antipsychotics. METHOD: Baseline and 1-year follow-up magnetic resonance images
      were obtained. Hippocampal volumes were estimated by using FreeSurfer and MAGeT
      Brain. Subgroups included: aripiprazole (n=13), olanzapine (n=12),
      risperidone/paliperidone (n=24), refused-antipsychotics (n=13) and controls
      (n=44). RESULTS: Aripiprazole subgroup displayed significant increases in
      bilateral hippocampal volume compared with all other subgroups (FreeSurfer: all
      P's<0.012; MAGeT-Brain: all P's<0.040). CONCLUSIONS: Aripiprazole is a first
      line, second-generation treatment option that may provide an added benefit of pro
      hippocampal growth. The biological underpinnings of these changes should be the
      focus of future investigations and may be key towards achieving a better clinical
      outcome for more individuals. DECLARATION OF INTEREST: M.L. received financial
      assistance/compensation for research and educational events from Janssen-Ortho,
      Eli Lilly, Roche and Otsuka/Lundbeck Alliance. A.K.M. received financial
      assistance/compensation for research and educational activities from Pfizer,
      Janssen-Ortho, AstraZeneca and Bristol-Myers Squibb. R.J. received consultancy
      honorariums from Pfizer and Janssen-Ortho. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2016. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703767
TI  - Mental capacity to consent to treatment in anorexia nervosa: explorative study.
AB  - BACKGROUND: Mental capacity to consent to treatment in anorexia nervosa is a
      neglected area in clinical decision-making. AIMS: To examine clinical and
      neuropsychological parameters associated with diminished mental capacity in
      anorexia nervosa. METHOD: An explorative study was conducted in 70 adult female
      patients with severe anorexia nervosa. Mental capacity to consent to treatment
      was assessed by experienced psychiatrists. Further measurements included the
      MacCAT-T (to assess mental capacity status), a range of clinical measures (body
      mass index (BMI) and comorbidity) and neuropsychological tests assessing decision
      making, central coherence and set-shifting capacity. RESULTS: Diminished mental
      capacity occurs in a third of patients with severe anorexia nervosa and is
      associated with a low BMI, less appreciation of illness and treatment, previous
      treatment for anorexia nervosa, low social functioning and poor set shifting.
      CONCLUSIONS: Assessment of diminished mental capacity in anorexia nervosa
      requires careful evaluation of not only BMI, but also the degree of appreciation
      of illness and treatment, history and the tendency to have a rigid thinking
      style. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College
      of Psychiatrists 2016. This is an open access article distributed under the terms
      of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703768
TI  - Internet cognitive-behavioural treatment for panic disorder: randomised
      controlled trial and evidence of effectiveness in primary care.
AB  - BACKGROUND: Internet cognitive-behavioural therapy (iCBT) for panic disorder of
      up to 10 lessons is well established. The utility of briefer programmes is
      unknown. AIMS: To determine the efficacy and effectiveness of a five-lesson iCBT
      programme for panic disorder. METHOD: Study 1 (efficacy): Randomised controlled
      trial comparing active iCBT (n=27) and waiting list control participants (n=36)
      on measures of panic severity and comorbid symptoms. Study 2 (effectiveness): 330
      primary care patients completed the iCBT programme under the supervision of
      primary care practitioners. RESULTS: iCBT was significantly more effective than
      waiting list control in reducing panic (g=0.97, 95% CI 0.34 to 1.61), distress
      (g=0.92, 95% CI 0.28 to 1.55), disability (g=0.81, 95% CI 0.19 to 1.44) and
      depression (g=0.79, 95% CI 0.17 to 1.41), and gains were maintained at 3 months
      post-treatment (iCBT group). iCBT remained effective in primary care, but lower
      completion rates were found (56.1% in study 2 v. 63% in study 1). Adherence
      appeared to be related to therapist contact. CONCLUSIONS: The five-lesson Panic
      Program has utility for treating panic disorder, which translates to primary
      care. Adherence may be enhanced with therapist contact. DECLARATION OF INTEREST:
      None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is
      an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703769
TI  - Testing the social competition hypothesis of depression using a simple economic
      game.
AB  - BACKGROUND: Price's social competition hypothesis interprets the depressive state
      as an unconscious, involuntary losing strategy, which enables individuals to
      yield and accept defeat in competitive situations. AIMS: We investigated whether
      patients who suffer from major depressive disorder (MDD) would avoid competition
      more often than either patients suffering from borderline personality disorder
      (BPD) or healthy controls. METHOD: In a simple paper-folding task healthy
      participants and patiens with MDD and BPD were matched with two opponents, one
      with an unknown diagnosis and one who shared their clinical diagnosis, and they
      had to choose either a competitive or cooperative payment scheme for task
      completion. RESULTS: When playing against an unknown opponent, but not the
      opponent with the same diagnosis, the patients with depression chose the
      competitive payment scheme statistically less often than healthy controls and
      patients diagnosed with BPD. CONCLUSION: The competition avoidance against the
      unknown opponent is consistent with Price's social competition hypothesis.
      DECLARATION OF INTEREST: G.H. received research support, consulting fees and
      speaker honoraria from Lundbeck, AstraZeneca, Servier, Eli Lilly, Roche and
      Novartis. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This
      is an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703770
TI  - Maternal vitamin D deficiency and the risk of autism spectrum disorders:
      population-based study.
AB  - BACKGROUND: Maternal vitamin D deficiency may increase risk of autism spectrum
      disorder (ASD), but direct evidence is lacking. AIMS: To clarify the relationship
      between maternal vitamin D deficiency and offspring risk of ASD with and without
      intellectual disability. METHOD: Using a register-based total population study
      (N=509 639), we calculated adjusted odds ratios (aORs) and 95% confidence
      intervals (CIs) of ASD with and without intellectual disability in relation to
      lifetime diagnoses of maternal vitamin D deficiency. Although rare, such
      deficiency was associated with offspring risk of ASD with, but not without,
      intellectual disability (aORs 2.51, 95% CI 1.22-5.16 and 1.28, 0.68-2.42).
      Relationships were stronger in non-immigrant children. CONCLUSIONS: If reflecting
      associations for prenatal hypovitaminosis, these findings imply gestational
      vitamin D substitution as a means of ASD prevention. DECLARATION OF INTEREST:
      None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is
      an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703771
TI  - The use of social environment in a psychosocial clubhouse to facilitate recovery
      oriented practice.
AB  - BACKGROUND: Recovery-oriented language has been widely adopted in mental health
      policy; however, little is known about how recovery practices are implemented
      within individual services, such as psychosocial clubhouses. AIMS: To explore how
      recovery practices are implemented in a psychosocial clubhouse. METHOD:
      Qualitative case study design informed by self-determination theory was utilised.
      This included 120 h of participant observation, interviews with 12 clubhouse
      members and 6 staff members. Field notes and interview transcripts were subject
      to theoretical thematic analysis. RESULTS: Two overarching themes were
      identified, each comprising three sub-themes. In this paper, the overarching
      theme of 'social environment' is discussed. It was characterised by the sub
      themes, 'community and consistency', 'participation and opportunity' and 'respect
      and autonomy'. CONCLUSIONS: Social environment was used to facilitate recovery
      oriented practice within the clubhouse. Whether recovery is experienced by
      clubhouse members in wider society, may well depend on supports and opportunities
      outside the clubhouse. DECLARATION OF INTERESTS: None. COPYRIGHT AND USAGE: (c)
      The Royal College of Psychiatrists 2016. This is an open access article
      distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703773
TI  - Morbidity and mortality of women and men with intellectual and developmental
      disabilities newly initiating antipsychotic drugs.
AB  - BACKGROUND: While up to 45% of individuals with intellectual and developmental
      disabilities (IDD) have a comorbid psychiatric disorder, and antipsychotics are
      commonly prescribed, gender differences in the safety of antipsychotics have
      rarely been studied in this population. AIMS: To compare men and women with IDD
      on medical outcomes after antipsychotic initiation. METHOD: Our population-based
      study in Ontario, Canada, compared 1457 women and 1951 men with IDD newly
      initiating antipsychotic medication on risk for diabetes mellitus, hypertension,
      venous thromboembolism, myocardial infarction, stroke and death, with up to 4
      years of follow-up. RESULTS: Women were older and more medically complex at
      baseline. Women had higher risks for venous thromboembolism (HR 1.72, 95% CI 1.15
      2.59) and death (HR 1.46, 95% CI 1.02-2.10) in crude analyses; but only
      thromboembolism risk was greater for women after covariate adjustment (aHR 1.58,
      95% CI 1.05-2.38). CONCLUSIONS: Gender should be considered in decision-making
      around antipsychotic medications for individuals with IDD. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703772
TI  - The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot
      multicentre, single-blind randomised trial of group cognitive-behavioural
      therapy.
AB  - BACKGROUND: There is a growing interest in using cognitive-behavioural therapy
      (CBT) with people who have Asperger syndrome and comorbid mental health problems.
      AIMS: To examine whether modified group CBT for clinically significant anxiety in
      an Asperger syndrome population is feasible and likely to be efficacious. METHOD:
      Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome
      were randomised into a treatment arm or a waiting-list control arm. After 24
      weeks, those in the waiting-list control arm received treatment, while those
      initially randomised to treatment were followed up for 24 weeks. RESULTS: The
      conversion rate for this trial was high (1.6:1), while attrition was 13%. After
      24 weeks, there was no significant difference between those randomised to the
      treatment arm compared with those randomised to the waiting-list control arm on
      the primary outcome measure, the Hamilton Rating Scale for Anxiety. CONCLUSIONS:
      Trials of psychological therapies with this population are feasible. Larger
      definitive trials are now needed. DECLARATION OF INTEREST: None. COPYRIGHT AND
      USAGE: (c) The Royal College of Psychiatrists 2016. This is an open access
      article distributed under the terms of the Creative Commons Attribution (CC BY)
      licence.

PMID- 27703774
TI  - A training programme involving automatic self-transcending meditation in late
      life depression: preliminary analysis of an ongoing randomised controlled trial.
AB  - : Late-life depression affects 2-6% of seniors aged 60 years and above. Patients
      are increasingly embracing non-pharmacological therapies, many of which have not
      been scientifically evaluated. This study aimed to evaluate a category of
      meditation, automatic self-transcending meditation (ASTM), in alleviating
      symptoms of depression when augmenting treatment as usual (NCT02149810). The
      preliminary results of an ongoing single-blind randomised controlled trial
      comparing a training programme involving ASTM with a wait-list control indicate
      that a 12-week ASTM programme may lead to significantly greater reductions in
      depression and anxiety severity. As such, ASTM may be an effective adjunctive
      therapy in the treatment of late-life depression. DECLARATION OF INTEREST: R.I.N.
      is Director of Research and Health Promotion for the Art of Living Foundation,
      Canada and supervised the staff providing ASTM training. COPYRIGHT AND USAGE: (c)
      The Royal College of Psychiatrists 2016. This is an open access article
      distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703775
TI  - Peacekeepers deserve more mental health research and care.
AB  - SUMMARY: United Nations peacekeeping personnel face numerous stressors due to
      their challenging deployments. Past studies have had inconsistent results
      regarding whether or not their deployment experience affects their mental health
      outcomes. Further studies are required to ascertain the associations between
      their outcomes and factors before, during and after their peacekeeping missions.
      DECLARATIONS OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2016. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703777
TI  - The feasibility and effectiveness of Catch It, an innovative CBT smartphone app.
AB  - BACKGROUND: The widespread use of smartphones makes effective therapies such as
      cognitive-behavioural therapy (CBT) potentially accessible to large numbers of
      people. AIMS: This paper reports the usage data of the first trial of Catch It, a
      new CBT smartphone app. METHOD: Uptake and usage rates, fidelity of user
      responses to CBT principles, and impact on reported negative and positive moods
      were assessed. RESULTS: A relatively modest proportion of people chose to
      download the app. Once used, the app tended to be used more than once, and 84% of
      the user-generated content was consistent with the basic concepts of CBT. There
      were statistically significant reductions in negative mood intensity and
      increases in positive mood intensity. CONCLUSIONS: Smartphone apps have potential
      beneficial effects in mental health through the application of basic CBT
      principles. More research with randomised controlled trial designs should be
      conducted. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2016. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703776
TI  - A cross-sectional study of problem gambling and its correlates among college
      students in South India.
AB  - BACKGROUND: In the Western world, a significant portion of college students have
      gambled. College gamblers have one of the highest rates of problem gambling. To
      date, there have been no studies on gambling participation or the rates of
      problem gambling in India. AIMS: This study evaluated the prevalence of gambling
      participation and problem gambling in college students in India. It also
      evaluated demographic and psychosocial correlates of gambling in that population.
      METHOD: We surveyed 5784 college students from 58 colleges in the district of
      Ernakulam, Kerala, India, using cluster random sampling. Students completed
      questionnaires that addressed gambling, substance use, psychological distress,
      suicidality and attention-deficit hyperactivity disorder (ADHD). RESULTS: A total
      of 5580 completed questionnaires were returned, and while only 1090 (19.5%)
      college students reported having ever gambled, 415 (7.4%) reported problem
      gambling. Lotteries were the most popular form of gambling. Problem gamblers in
      comparison with non-gamblers were significantly more likely to be male, have a
      part-time job, greater academic failures, higher substance use, higher
      psychological distress scores, higher suicidality and higher ADHD symptom scores.
      In comparison with non-problem gamblers, problem gamblers were significantly more
      likely to have greater academic failures, higher psychological distress scores,
      higher suicidality and higher ADHD symptom scores. CONCLUSIONS: This study, the
      first to look at the prevalence of gambling in India, found relatively low rates
      of gambling participation in college students but high rates of problem gambling
      among those who did gamble. Correlates of gambling were generally similar to
      those noted in other countries. Since 38% of college students who had gambled had
      a gambling problem, there is a need for immediate public health measures to raise
      awareness about gambling, and to prevent and treat problem gambling in this
      population. DECLARATION OF INTEREST: S.G. was (until October 2014) a member of
      the UK Responsible Gambling Strategy Board, and authored the Royal College of
      Psychiatrists' Faculty report FR/AP/01 Gambling: The Hidden Addiction - Future
      Trends in Addictions (2014). COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2016. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703779
TI  - 'He left me a message on Facebook': comparing the risk profiles of self-harming
      patients who leave paper suicide notes with those who leave messages on new
      media.
AB  - BACKGROUND: In cases of non-fatal self-harm, suicide notes are a major risk
      factor for repeated self-harm and suicide. Suicide notes can now be left on new
      media services, emails or text messages, as well as on paper. AIMS: In a group of
      people who had harmed themselves, we aimed to compare new media note-leavers with
      paper note-leavers and characterise these groups demographically and by risk
      factors. METHOD: Clinical notes of patients who presented with non-fatal self
      harm to two London emergency departments were anonymously searched for mentions
      of new media use. These were categorised and risk factors were compared for those
      who had left a new media note, a paper note, or no note to establish differences
      in risk of note-leaving. RESULTS: New media note-leaving was associated with
      younger age and substance use; both risk factors for repeated self-harm. However,
      suicidal intent remained highest in paper note-leavers. CONCLUSIONS: Paper note
      leavers remain at greatest risk, however new media note leaving is still
      correlated with risk factors related to repeated self-harm and suicide.
      Clinicians should enquire about new media use during emergency department
      assessments of self-harm. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c)
      The Royal College of Psychiatrists 2016. This is an open access article
      distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) licence.

PMID- 27703778
TI  - Asperger syndrome in childhood - personality dimensions in adult life:
      temperament, character and outcome trajectories.
AB  - BACKGROUND: Temperament and character have been shown to be important factors in
      understanding psychiatric and neurodevelopmental disorder. Adults with autism
      spectrum disorder (ASD) have repeatedly been shown to have a distinct temperament
      and character, but this has not been evaluated in relation to psychiatric
      comorbidity and ASD diagnostic stability. AIMS: To examine temperament and
      character in males that were diagnosed with ASD in childhood and followed
      prospectively over almost two decades. METHOD: Temperament and character were
      assessed in 40 adult males with a childhood diagnosis of ASD. Results were
      analysed by the stability of ASD diagnosis over time and current psychiatric
      comorbidity. RESULTS: Three distinct temperament and character profiles emerged
      from the data. Those no longer meeting criteria for ASD had high reward
      dependence while those with a stable ASD diagnosis and psychiatric comorbidity
      showed elevated harm avoidance and low self-directedness and cooperativeness.
      Finally, those with a stable ASD and no comorbidity showed low novelty seeking
      and somewhat elevated harm avoidance. CONCLUSIONS: Temperament and character are
      important factors correlated with long-term diagnostic stability and psychiatric
      comorbidity in males diagnosed with ASD in childhood. DECLARATION OF INTEREST:
      None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is
      an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703780
TI  - Mental disorders in new parents before and after birth: a population-based cohort
      study.
AB  - BACKGROUND: Mental disorders of women during the postnatal period are a major
      public health problem. Compared with women's mental disorders, much less
      attention has been paid to men's mental disorders in the perinatal period. To
      date, there have been no reports in the literature describing secular changes of
      both maternal and paternal hospital admissions for mental disorders over the
      period covering the year before pregnancy (non-parents), during pregnancy
      (expectant parents) and up to the first year after birth (parents) based on
      linked parental data. The co-occurrences of couples' hospital admissions for
      mental disorders have not previously been investigated. AIMS: To describe
      maternal and paternal hospital admissions for mental disorders before and after
      birth. To compare the co-occurrences of parents' hospital admissions for mental
      disorder in the perinatal period. METHOD: This is a cohort study using paired
      parents' population data from the New South Wales (NSW) Perinatal Data Collection
      (PDC), Registry of Births, Deaths and Marriages (RBDM) and Admitted Patients Data
      Collection (APDC). The study included all parents (n=196 669 couples) who gave
      birth to their first child in NSW between 1 January 2003 and 31 December 2009.
      RESULTS: The hospital admission rate for women with a principal mental disorder
      diagnosis in the period between the year before pregnancy and the first year
      after birth was significantly higher than that for men. Parents' mental disorders
      influenced each other. If a man was admitted to hospital with a principal mental
      disorder diagnosis, his wife or partner was more likely to be admitted to
      hospital with a principal mental disorder diagnosis compared with women whose
      partner had not had a hospital admission, and vice versa. CONCLUSIONS: Mothers'
      mental disorders after birth increased more significantly than fathers. However,
      fathers' mental disorders significantly impacted the co-occurrence of mothers'
      mental disorders. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The
      Royal College of Psychiatrists 2016. This is an open access article distributed
      under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC
      ND) licence.

PMID- 27703781
TI  - Inflammatory response to clozapine in the absence of myocarditis: case report.
AB  - SUMMARY: A case is presented of a 25-year-old man with treatment-resistant
      paranoid schizophrenia whose only previous trial of clozapine had been stopped
      following a suspected clozapine-induced myocarditis. Due to the failure of his
      psychosis to respond to a number of antipsychotic treatments and augmentation
      strategies, clozapine was restarted on admission. His rechallenge was marked by
      intermittent pyrexia, tachycardia and elevated C-reactive protein (CRP), but
      eosinophilia was absent. Clozapine was started and then stopped twice following
      extensive investigation and with specialist cardiology consultation. Physical
      symptoms and CRP elevation resolved shortly after clozapine cessation. We believe
      this constituted an idiosyncratic systemic inflammatory response to clozapine
      treatment. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2016. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703782
TI  - Ketamine: stimulating antidepressant treatment?
AB  - SUMMARY: The appeal of ketamine - in promptly ameliorating depressive symptoms
      even in those with non-response - has led to a dramatic increase in its off-label
      use. Initial promising results await robust corroboration and key questions
      remain, particularly concerning its long-term administration. It is, therefore,
      timely to review the opinions of mood disorder experts worldwide pertaining to
      ketamine's potential as an option for treating depression and provide a synthesis
      of perspectives - derived from evidence and clinical experience - and to consider
      strategies for future investigations. DECLARATION OF INTERESTS: G.S.M.
      Grant/research support: National Health Medical Research Council, NSW Health,
      Ramsay Health, American Foundation for Suicide Prevention, AstraZeneca, Eli Lilly
      & Co, Organon, Pfizer, Servier, and Wyeth; has been a speaker for Abbott,
      AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier,
      and Wyeth; consultant: AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, and
      Servier. M.A.F. Grant support: AssureRx, Janssen Research & Development, Mayo
      Foundation, Myriad, National Institute of Alcohol Abuse and Alcoholism (NIAAA),
      National Institute of Mental Health (NIMH), Pfizer. Consultant (Mayo): Janssen
      Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Myriad
      Genetics, Neuralstem Inc., Sunovion, Supernus Pharmaceuticals, Teva
      Pharmaceuticals. CME/travel support: American Physician Institute, CME
      Outfitters. Financial interest/Mayo Clinic 2016: AssureRx. S.H.K. Grant/research
      support: Brain Canada, Bristol Meyer Squibb, CIHR, Janssen, Johnson & Johnson,
      Lundbeck, Ontario Brain Institute, Pfizer, Servier, St. Jude Medical, Sunovion.
      T.A.K. Grant/research support (through Stanford University): Sunovion
      Pharmaceuticals and Merck & Co., Inc.; consultant/advisory board bember:
      Allergan, Inc., Janssen Pharmaceuticals, Myriad Genetic Laboratories, Inc., and
      Sunovion Pharmaceuticals; lecture honoraria (not Speaker's Bureau payments):
      GlaxoSmithKline, and Sunovion Pharmaceuticals; royalties from American
      Psychiatric Publishing, Inc. Also, AstraZeneca Pharmaceuticals LP provided
      publication support to Parexel for preparation of a manuscript. Spouse employee
      and stockholder of Janssen Pharmaceuticals. R.W.L. Honoraria for
      speaking/advising/consulting, and/or received research funds: AstraZeneca, Brain
      Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian
      Depression Research and Intervention Network, Canadian Network for Mood and
      Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings,
      Johnson and Johnson, Lundbeck, Lundbeck Institute, Pfizer, Servier, St. Jude
      Medical, Takeda University, Health Network Foundation, and Vancouver Coastal
      Health Research Institute. R.M. Investigator Janssen trials of esketamine; 'paid
      for' ketamine clinic operated by Oxford Health NHS Foundation Trust - fees used
      to support the Trust. M.J.O. Consultant: Sunovion and Acadia Pharmaceuticals.
      Full-time employee of U.S. Department of Veterans Affairs. M.E.T.
      Advisory/Consultant: Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb
      Company, Cerecor inc., Eli Lilly & Co., Forest Laboratories, Gerson Lehrman
      Group, Fabre-Kramer Pharmaceuticals, Inc., GlaxoSmithKline, Guidepoint Global, H.
      Lundbeck A/S, MedAvante Inc., Merck and Co. Inc. (formerly Schering Plough and
      Organon), Moksha8, Naurex Inc., Neuronetics Inc., Novartis, Ortho-McNeil
      Pharmaceuticals (Johnson & Johnson; Janssen), Otsuka, Pamlab, L.L.C. (Nestle),
      Pfizer (formerly Wyeth Ayerst Pharmaceuticals), Shire US Inc., Sunovion
      Pharmaceuticals Inc., Trius Therapeutical Inc. and Takeda. Grant support: Agency
      for Healthcare Research and Quality, Alkermes, AssureRx, Avanir, Forest
      Pharmaceuticals, Janssen, National Institute of Mental Health, and Otsuka
      Pharmaceuticals. Speakers Bureau: None since June, 2010. Equity Holdings:
      MedAvante, Inc. Royalties: American Psychiatric Foundation, Guilford
      Publications, Herald House, W.W. Norton & Company, Inc. Spouse's employment:
      Peloton Advantage, which does business with Pfizer. M.T. Full-time employee at
      Lilly 1997 to 2008. Honoraria/consulted: Abbott, AstraZeneca, Bristol Myers
      Squibb, GlaxoSmithKline, Lilly, Johnson & Johnson, Allergan, Otsuka, Merck,
      Sunovion, Forest, Geodon Richter Plc, Roche, Elan, Alkermes, Lundbeck, Teva,
      Pamlab, Minerva, Wyeth and Wiley Publishing. Spouse was full time-employee at
      Lilly 1998-2013. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists
      2016. This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703783
TI  - Diagnostic potential of structural neuroimaging for depression from a multi
      ethnic community sample.
AB  - BACKGROUND: At present, we do not have any biological tests which can contribute
      towards a diagnosis of depression. Neuroimaging measures have shown some
      potential as biomarkers for diagnosis. However, participants have generally been
      from the same ethnic background while the applicability of a biomarker would
      require replication in individuals of diverse ethnicities. AIMS: We sought to
      examine the diagnostic potential of the structural neuroanatomy of depression in
      a sample of a wide ethnic diversity. METHOD: Structural magnetic resonance
      imaging (MRI) scans were obtained from 23 patients with major depressive disorder
      in an acute depressive episode (mean age: 39.8 years) and 20 matched healthy
      volunteers (mean age: 38.8 years). Participants were of Asian, African and
      Caucasian ethnicity recruited from the general community. RESULTS: Structural
      neuroanatomy combining white and grey matter distinguished patients from controls
      at the highest accuracy of 81% with the most stable pattern being at around 70%.
      A widespread network encompassing frontal, parietal, occipital and cerebellar
      regions contributed towards diagnostic classification. CONCLUSIONS: These
      findings provide an important step in the development of potential neuroimaging
      based tools for diagnosis as they demonstrate that the identification of
      depression is feasible within a multi-ethnic group from the community.
      DECLARATION OF INTERESTS: C.H.Y.F. has held recent research grants from Eli Lilly
      and Company and GlaxoSmithKline. L.M. is a former employee and stockholder of Eli
      Lilly and Company. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists
      2016. This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

PMID- 27703784
TI  - Increased anticipatory but decreased consummatory brain responses to food in
      sisters of anorexia nervosa patients.
AB  - BACKGROUND: We have previously shown increased anticipatory and consummatory
      neural responses to rewarding and aversive food stimuli in women recovered from
      anorexia nervosa (AN). AIMS: To determine whether these differences are trait
      markers for AN, we examined the neural response in those with a familial history
      but no personal history of AN. METHOD: Thirty-six volunteers were recruited: 15
      who had a sister with anorexia nervosa (family history) and 21 control
      participants. Using fMRI we examined the neural response during an anticipatory
      phase (food cues, rewarding and aversive), an effort phase and a consummatory
      phase (rewarding and aversive tastes). RESULTS: Family history (FH) volunteers
      showed increased activity in the caudate during the anticipation of both reward
      and aversive food and in the thalamus and amygdala during anticipation of
      aversive only. FH had decreased activity in the dorsal anterior cingulate cortex,
      the pallidum and the superior frontal gyrus during taste consumption.
      CONCLUSIONS: Increased neural anticipatory but decreased consummatory responses
      to food might be a biomarker for AN. Interventions that could normalise these
      differences may help to prevent disorder onset. DECLARATION OF INTEREST: C.M. has
      acted as a consultant to P1VITAL, Givaudan, GWPharma, the British Broadcasting
      Corporation (BBC) and Channel 4. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2016. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 27703785
TI  - Cost-effectiveness of telehealth for patients with depression: evidence from the
      Healthlines randomised controlled trial.
AB  - BACKGROUND: Depression is a prevalent long-term condition that is associated with
      substantial resource use. Telehealth may offer a cost-effective means of
      supporting the management of people with depression. AIMS: To investigate the
      cost-effectiveness of a telehealth intervention ('Healthlines') for patients with
      depression. METHOD: A prospective patient-level economic evaluation conducted
      alongside a randomised controlled trial. Patients were recruited through primary
      care, and the intervention was delivered via a telehealth service. Participants
      with a confirmed diagnosis of depression and PHQ-9 score >=10 were recruited from
      43 English general practices. A series of up to 10 scripted, theory-led,
      telephone encounters with health information advisers supported participants to
      effect a behaviour change, use online resources, optimise medication and improve
      adherence. The intervention was delivered alongside usual care and was designed
      to support rather than duplicate primary care. Cost-effectiveness from a combined
      health and social care perspective was measured by net monetary benefit at the
      end of 12 months of follow-up, calculated from incremental cost and incremental
      quality-adjusted life years (QALYs). Cost-consequence analysis included cost of
      lost productivity, participant out-of-pocket expenditure and the clinical
      outcome. RESULTS: A total of 609 participants were randomised - 307 to receive
      the Healthlines intervention plus usual care and 302 to receive usual care alone.
      Forty-five per cent of participants had missing quality of life data, 41% had
      missing cost data and 51% of participants had missing data on either cost or
      utility, or both. Multiple imputation was used for the base-case analysis. The
      intervention was associated with incremental mean per-patient National Health
      Service/personal social services cost of L168 (95% CI L43 to L294) and an
      incremental QALY gain of 0.001 (95% CI -0.023 to 0.026). The incremental cost
      effectiveness ratio was L132 630. Net monetary benefit at a cost-effectiveness
      threshold of L20 000 was -L143 (95% CI -L164 to -L122) and the probability of the
      intervention being cost-effective at this threshold value was 0.30. Productivity
      costs were higher in the intervention arm, but out-of-pocket expenses were lower.
      CONCLUSIONS: The Healthlines service was acceptable to patients as a means of
      condition management, and response to treatment after 4 months was higher for
      participants randomised to the intervention. However, the positive average
      intervention effect size was modest, and incremental costs were high relative to
      a small incremental QALY gain at 12 months. The intervention is not likely to be
      cost-effective in its current form. DECLARATION OF INTEREST: None. COPYRIGHT AND
      USAGE: (c) The Royal College of Psychiatrists 2016. This is an open access
      article distributed under the terms of the Creative Commons Attribution (CC BY)
      licence.

PMID- 27703786
TI  - Psychosocial aspects of epilepsy: a wider approach.
AB  - SUMMARY: Epilepsy is one of the most serious neurological conditions and has an
      impact not only on the affected individual but also on the family and,
      indirectly, on the community. A global approach to the individual must take into
      account cognitive problems, psychiatric comorbidities and all psychosocial
      complications that often accompany epilepsy. We discuss psychosocial issues in
      epilepsy with special focus on the relationship between stigma and psychiatric
      comorbidities. Social barriers to optimal care and health outcomes for people
      with epilepsy result in huge disparities, and the public health system needs to
      invest in awareness programmes to increase public knowledge and reduce stigma in
      order to minimise such disparities. DECLARATIONS OF INTEREST: J.W.S. receives
      research support from the Dr Marvin Weil Epilepsy Research Fund, Eisai,
      GlaxoSmithKline, the World Health Organization and the EU's FP7 programme, and
      has been consulted by, and has received fees for lectures from, GlaxoSmithKline,
      Eisai, Lundbeck, Teva and UCB. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2016. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 27703787
TI  - The association between borderline personality disorder, fibromyalgia and chronic
      fatigue syndrome: systematic review.
AB  - BACKGROUND: Overlap of aetiological factors and demographic characteristics with
      clinical observations of comorbidity has been documented in fibromyalgia
      syndrome, chronic fatigue syndrome (CFS) and borderline personality disorder
      (BPD). AIMS: The purpose of this study was to assess the association of BPD with
      fibromyalgia syndrome and CFS. The authors reviewed literature on the prevalence
      of BPD in patients with fibromyalgia or CFS and vice versa. METHODS: A search of
      five databases yielded six eligible studies. A hand search and contact with
      experts yielded two additional studies. We extracted information pertaining to
      study setting and design, demographic information, diagnostic criteria and
      prevalence. RESULTS: We did not identify any studies that specifically assessed
      the prevalence of fibromyalgia or CFS in patients with BPD. Three studies
      assessed the prevalence of BPD in fibromyalgia patients and reported prevalence
      of 1.0, 5.25 and 16.7%. Five studies assessed BPD in CFS patients and reported
      prevalence of 3.03, 1.8, 2.0, 6.5 and 17%. CONCLUSIONS: More research is required
      to clarify possible associations between BPD, fibromyalgia and CFS. DECLARATION
      OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists
      2016. This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 27703789
TI  - Bulking up the hippocampus in schizophrenia: a role for 5-HT1A agonists?
AB  - SUMMARY: The volume of the hippocampus is reduced in patients with schizophrenia,
      and this deficit tends to become more pronounced with chronicity. Newer
      antipsychotics may protect against the progressive reductions in hippocampal
      volume while preliminary data offer hope that specific antipsychotics may act to
      reverse it. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2016. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      licence.

PMID- 27703788
TI  - Personality traits in adults with attention-deficit hyperactivity disorder and
      their unaffected first-degree relatives.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) shows clear, albeit
      heterogeneous, cognitive dysfunctions. However, personality traits are not well
      understood in adults with ADHD, and it is unclear whether they are predisposing
      factors or phenotypical facets of the condition. AIMS: To assess whether
      personality traits of impulsivity, sensation seeking and sensitivity to
      punishment and reward are predisposing factors for ADHD or aspects of the
      clinical phenotype. METHOD: Twenty adults with ADHD, 20 unaffected first-degree
      relatives and 20 controls completed rating scales assessing traits of
      impulsivity, sensation seeking and sensitivity to punishment/reward. RESULTS:
      Compared with relatives and controls, individuals with ADHD showed increased
      impulsive personality traits, were more susceptible to boredom and presented
      hypersensitivity to reward but normal sensitivity to punishment. CONCLUSIONS:
      High impulsivity traits, heightened sensitivity to reward and boredom are
      associated with the phenotype of ADHD, rather than being predisposing factors, as
      these traits were not shared between ADHD probands and their relatives.
      DECLARATION OF INTEREST: E.T.B. is employed part-time by GSK and part-time by the
      University of Cambridge; he holds stock in GSK. B.J.S. consults for Cambridge
      Cognition, Servier and Lundbeck; she holds a grant from Janssen/J&J. U.M. has
      received honoraria for consultancy and speaking at conferences and travel
      expenses from Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Pharmacia
      Upjohn and UCB Pharma. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2016. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 27703790
TI  - In an open publishing house not so far, far away....
AB  - SUMMARY: As BJPsych Open completes its first circle around the sun and marks its
      first anniversary, we share with you its strengths and advantages that underpin
      its success as a new journal. First and foremost, the editorial team has
      maintained rigorous scientific standards while pursuing an open access publishing
      model that, by design, accommodates a broad range of clinical and scientific
      topics. Fundamental to BJPsych Open's mission has been our policy of accepting
      papers that are both methodologically sound and intellectually stimulating. The
      calibre of the journal has already been recognised, with recent notification of
      indexing all its content in PubMed Central. This reflects the quality of
      submissions and is the result of concerted efforts by the authors, the editorial
      board, the many selfless reviewers and our dedicated staff in the journal office.
      We urge you to join us on this exciting journey and look to your input as
      authors, readers and reviewers to help shape this fledgling enterprise, destined
      to become a force to be reckoned with. DECLARATION OF INTERESTS: None. COPYRIGHT
      AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open access
      article distributed under the terms of the Creative Commons Non-Commercial, No
      Derivatives (CC BY-NC-ND) license.

PMID- 27703791
TI  - Initiation of pharmacotherapy for post-traumatic stress disorder among veterans
      from Iraq and Afghanistan: a dimensional, symptom cluster approach.
AB  - BACKGROUND: The pharmacological treatment of post-traumatic stress disorder
      (PTSD) is extremely challenging, as no specific agent has been developed
      exclusively to treat this disorder. Thus, there are growing concerns among the
      public, providers and consumers associated with its use as the efficacy of some
      agents is still in question. AIMS: We applied a dimensional and symptom cluster
      based approach to better understand how the heterogeneous phenotypic presentation
      of PTSD may relate to the initiation of pharmacotherapy for PTSD initial episode.
      METHOD: US veterans who served in the conflicts in Iraq and Afghanistan and
      received an initial PTSD diagnosis at the US Veterans Health Administration
      between 2008 and 2011 were included in this study. Veterans were followed for 365
      days from initial PTSD diagnosis to identify initiation for antidepressants,
      anxiolytics/sedatives/hypnotics, antipsychotics and prazosin. Multivariable
      analyses were used to assess the relationship between the severity of unique PTSD
      symptom clusters and receiving prescriptions from each medication class, as well
      as the time from diagnosis to first prescription. RESULTS: Increased severity of
      emotional numbing symptoms was independently associated with the prescription of
      antidepressants, and they were prescribed after a substantially shorter period of
      time than other medications. Anxiolytics/sedatives/hypnotics prescription was
      associated with heightened re-experiencing symptoms and sleep difficulties.
      Antipsychotics were associated with elevated re-experiencing and numbing symptoms
      and prazosin with reported nightmares. CONCLUSIONS: Prescribing practices for
      military-related PTSD appear to follow US VA/DoD clinical guidelines. Results of
      this study suggest that a novel dimensional and symptom cluster-based approach to
      classifying the phenotypic presentation of military-related PTSD symptoms may
      help inform prescribing patterns for PTSD. DECLARATION OF INTEREST: None.
      COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open
      access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 27703792
TI  - Women with bipolar disorder and pregnancy: factors influencing their decision
      making.
AB  - BACKGROUND: Women with bipolar disorder are at increased risk of having a severe
      episode of illness associated with childbirth. AIMS: To explore the factors that
      influence the decision-making of women with bipolar disorder regarding pregnancy
      and childbirth. METHOD: Qualitative study with a purposive sample of women with
      bipolar disorder considering pregnancy, or currently or previously pregnant,
      supplemented by data from an online forum. Data were analysed using thematic
      analysis. RESULTS: Twenty-one women with bipolar disorder from an NHS
      organisation were interviewed, and data were used from 50 women's comments via
      the online forum of the UK's national bipolar charity. The centrality of
      motherhood, social and economic contextual factors, stigma and fear were major
      themes. Within these themes, new findings included women considering an elective
      Caesarian section in an attempt to avoid the deleterious effects of a long labour
      and loss of sleep, or trying to avoid the risks of pregnancy altogether by means
      of adoption or surrogacy. CONCLUSIONS: This study highlights the information
      needs of women with bipolar disorder, both pre-conception and when childbearing,
      and the need for improved training for all health professionals working with
      women with bipolar disorder of childbearing age to reduce stigmatising attitudes
      and increase knowledge of the evidence base on treatment in the perinatal period.
      DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2016. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 27703793
TI  - GADL1 variant and medication adherence in predicting response to lithium
      maintenance treatment in bipolar I disorder.
AB  - BACKGROUND: Genetic variants and medication adherence have been identified to be
      the main factors contributing to lithium treatment response in bipolar disorders.
      AIMS: To simultaneously examine effects of variant glutamate decarboxylase-like
      protein 1 (GADL1) and medication adherence on response to lithium maintenance
      treatment in Han Chinese patients with bipolar I (BPI) disorder. METHOD:
      Frequencies of manic and depressive episodes between carriers and non-carriers of
      the effective GADL1 rs17026688 T allele during the cumulative periods of off
      lithium, poor adherence to lithium treatment and good adherence to lithium
      treatment were compared in Han Chinese patients with BPI disorder (n=215).
      RESULTS: GADL1 rs17026688 T carriers had significantly lower frequencies of
      recurrent affective episodes than non-T carriers during the cumulative period of
      good adherence, but not during those of poor adherence. CONCLUSIONS: GADL1
      rs17026688 and medication adherence jointly predict response to lithium
      maintenance treatment in Han Chinese BPI patients. DECLARATION OF INTEREST: None.
      COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open
      access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 27703794
TI  - Internet-delivered treatment for older adults with anxiety and depression:
      implementation of the Wellbeing Plus Course in routine clinical care and
      comparison with research trial outcomes.
AB  - BACKGROUND: The Wellbeing Plus Course is an internet-delivered psychological
      intervention for older adults with anxiety or depression. AIMS: To compare the
      effectiveness of the Wellbeing Plus Course in a public health setting (clinic
      group) with its efficacy in a randomised controlled trial (research group).
      METHOD: Participants (n=949) were Australian adults aged 60 and above. Primary
      outcome measures were the Patient Health Questionnaire (PHQ-9) and Generalized
      Anxiety Disorder scale (GAD-7). RESULTS: Initial symptom severity was higher in
      the clinic group and course completion was lower. Both groups showed significant
      symptom reductions at post-treatment and were satisfied with the treatment.
      Results were maintained at 3-month follow-up. Within-group symptom changes were
      comparable between settings; there were no between-group differences on primary
      outcomes or satisfaction. CONCLUSIONS: The Wellbeing Plus Course is as effective
      and acceptable in routine clinical care, as it is in controlled research trials.
      DECLARATION OF INTEREST: N.T. and B.F.D developed the Wellbeing Plus Course but
      derived no financial benefit from it. COPYRIGHT AND USAGE: (c) The Royal College
      of Psychiatrists 2016. This is an open access article distributed under the terms
      of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 27703795
TI  - Heart Attack in the Course of Lithium Overdose.
AB  - INTRODUCTION: Lithium overdose can be associated with cardiac toxicity,
      especially in those with underlying heart disease. Toxic levels of serum lithium
      are associated with cardiotoxic effects ranging from simple ECG disorders to
      dysrhythmias, cardiomyopathy and even acute myocardial infarction (AMI). This
      report describes a patient with AMI accompanied by high blood levels of lithium.
      CASE PRESENTATION: A 62-year-old woman was admitted to the emergency department
      due to weakness and acute chest pain. Her ECG revealed ST elevation in leads DI,
      aVL and V5-6, with a ventricular rate of 80 bpm. Blood chemistry and complete
      blood count were within normal limits. The patient's blood lithium level was
      measured as 2.3 mmol/L (N: 0.5 - 0.8 mmol/L), and her troponin I level was 0.892
      ng/mL (N: 0 - 0.01 ng/mL). Coronary angiography produced normal findings,
      concurrent with the resolution of electrocardiographic abnormalities following
      elimination of lithium. The clinical course in the intensive care unit was
      uneventful and the patient was discharged on the seventh day. CONCLUSIONS:
      Lithium intoxication should be considered in the differential diagnosis,
      especially in elderly patients on lithium therapy who are admitted to the
      emergency department with chest pain.

PMID- 27703796
TI  - Comparing the Excessive Daytime Sleepiness of Obese and Non-obese Patients.
AB  - BACKGROUND: Obesity, particularly morbid obesity, has various physical and mental
      complications. Excessive daytime somnolence (EDS) is a sleep disorder that
      reduces individuals' performance capability and the accuracy of their short-term
      memory and causes learning problems. This retrospective study aimed to document
      the presence of EDS in a sample of obese patients in comparison to patients with
      a normal weight. OBJECTIVES: This article compares the excessive daytime
      sleepiness of obese and non-obese patients in the minimally invasive surgery
      research center in Tehran, Iran. PATIENTS AND METHODS: In this case-control
      study, we compared excessive daytime sleepiness in 55 obese patients who were
      candidates for laparoscopic surgery, with a body mass index (BMI) of equal to or
      greater than 30 kg/ m2, with 55 controls with a normal BMI (19.5 - 24.9 kg/ m2).
      The process of selecting the control group in our case-control study is matching
      in group levels, so that the controls are similar to the case group with regard
      to certain key characteristics, such as age, sex, and race. The sleep assessment
      was based on the Epworth sleepiness scale (ESS) questionnaire. Analysis of
      variance (ANOVA) was used to compare the means of quantitative data, such as the
      ESS score of groups. RESULTS: Sleepiness was not affected by gender in cases or
      controls. The sleepiness prevalence was 29 (52.7%) in the cases group and 17
      (30.9%) in the control group (OR = 2.493 (95% CI 1.144 -5.435)). The mean ESS
      scores in cases and controls were 7.82 +/- 3.86 and 10.54 +/- 6.15, respectively
      (P = 0.007). Moreover, the prevalence of sleepiness and the mean ESS scores in
      class III of obesity differed significantly from the controls (16 (57.1%) vs. 17
      (30.9%)) (OR = 2.980 (95% CI 1.162 - 7.645)) and (11.04 +/- 5.93 vs. 7.82 +/-
      3.86) (P = 0.013), respectively. CONCLUSIONS: Our findings suggest a strong
      relationship between EDS and obesity, particularly morbid obesity. Therefore,
      physicians must be familiar with EDS as a mixed clinical entity indicating
      careful assessment and specific treatment planning.

PMID- 27703797
TI  - Participation a Key Factor for Life Recovery After Disaster: A Grounded Theory
      Study in an Iranian Context.
AB  - BACKGROUND: Since life recovery after disasters is a subjective and multifaceted
      construct influenced by different factors, and survivors' main concerns and
      experiences are not clear, the researchers intended to explore this process.
      MATERIALS AND METHODS: This study was conducted in 2011 - 2014 based on the
      grounded theory approach. Participants were selected by purposeful sampling
      followed by theoretical sampling to achieve conceptual and theoretical
      saturation. Data were collected through interviews, observation, focus group
      discussion, and document reviews. Data were analyzed by Strauss and Corbin's
      (2008) recommended approach. RESULTS: Transcribed data from 26 interviews
      (managers, health care providers, and receivers), field notes, and other
      documents were analyzed, and 1,652 open codes were identified. The codes were
      categorized, using constant comparative analysis, into five main categories
      including reactive exposure, subsiding emotions, need for comprehensive health
      recovery, improvement of normalization (new normality achievement), and
      contextual factors. The process of life recovery after disaster was also
      explored. CONCLUSIONS: The results clarified a deep perception of participants'
      experiences after disaster. The path of life recovery after disasters involves
      participants' striving to achieve a comprehensive health recovery, which starts
      with the need for all-inclusive health recovery as a main concern; this is the
      motivator for a responding strategy. This strategy is participatory, and the
      process is progressive; achievement of a new normality is the final goal, with
      new development and levels of empowerment.

PMID- 27703798
TI  - Umbelliprenin is Potentially Toxic Against the HT29, CT26, MCF-7, 4T1, A172, and
      GL26 Cell Lines, Potentially Harmful Against Bone Marrow-Derived Stem Cells, and
      Non-Toxic Against Peripheral Blood Mononuclear Cells.
AB  - BACKGROUND: Resistance to chemotherapy is a growing concern, thus natural
      anticancer agents are drawing the attention of many scientists and clinicians.
      One natural anticancer agent, umbelliprenin, is a coumarin produced by many
      species of Ferula. OBJECTIVES: We aimed to examine the inhibitory effect of
      umbelliprenin on human and mouse bone marrow-derived stem cells (BMDSCs),
      peripheral blood mononuclear cells (PBMCs), and different cancer cell lines.
      MATERIALS AND METHODS: In this in vitro experimental study, the HT29, CT26, MCF
      7, 4T1, A172, and GL26 cancer cells and human and mouse BMDSCs and PBMCs were
      cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS),
      incubated at 37 degrees C for 24 hours in a 5% CO2 atmosphere, and then were
      treated with different concentrations of umbelliprenin dissolved in dimethyl
      sulfoxide (DMSO) (3, 6, 12, 25, 50, 100, and 200 ug/mL) for 24, 48, and 72 hours
      at 37 degrees C. Each experiment was performed in triplicate. Finally, the cell
      survival rate was assessed by MTT assay. The IC50 values were calculated based on
      the log values using GraphPad Prism version 5 software for windows (La Jolla CA,
      USA) and were expressed as mean +/- SEM. RESULTS: Umbelliprenin inhibited the
      cancer cells in a concentration-dependent (P < 0.05) but not time-dependent
      manner (P > 0.05). The most sensitive and resistant cell lines at the 24-hour
      incubation time were 4T1 (IC50, 30.9 +/- 3.1 ug/mL) and A172 (IC50, 51.9 +/- 6.7
      ug/mL); at the 48-hour incubation time: 4T1 (IC50, 30.6 +/- 2.6 ug/mL) and CT26
      (IC50, 53.2 +/- 3.6 ug/mL); and at the 72-hour incubation time: HT29 (IC50, 37.1
      +/- 1.4 ug/mL) and 4T1 (IC50, 62.2 +/- 4.8 ug/mL). Both human and mouse BMDSCs
      showed the highest resistance at the 24-hour incubation time (IC50s, 254.7 +/- 21
      and 204.4 +/- 4.5 ug/mL, respectively) and the highest sensitivity at the 72-hour
      incubation time (IC50s, 120.4 +/- 5 and 159.0 +/- 7.3 ug/mL, respectively). The
      PBMCs of both human and mouse origin revealed very strong resistance to the
      studied concentrations of umbelliprenin (IC50s ranging from 713.5 +/- 499.1 to
      6651 +/- 3670.7 ug/mL). CONCLUSIONS: Our findings indicate that umbelliprenin
      exhibits concentration-dependent inhibitory effects on various cell types; it is
      potentially toxic against the HT29, CT26, MCF-7, 4T1, A172, and GL26 cell lines,
      potentially harmful against BMDSCs, and non-toxic against PBMCs. Therefore, if
      our results are approved in the future, umbelliprenin can be an appropriate
      candidate for developing treatments against different cancers.

PMID- 27703799
TI  - Psychometric Properties of the Iranian Version of a Postpartum Women's Quality of
      Life Questionnaire (PQOL): A Methodological Study.
AB  - BACKGROUND: There are some specific measures for the evaluation of postpartum
      quality of life, and each have some limitations. OBJECTIVES: This study
      investigated the validity and reliability of the Persian version of a postpartum
      women's quality of life (PQOL) questionnaire at the eighth week of postpartum.
      PATIENTS AND METHODS: This was a methodological research, and subjects were 500
      women, ages 18 - 42, eight weeks postpartum, randomly selected from half of the
      public centers in Tabriz, Iran, who completed questionnaires in a self
      administered manner. Data was collected during a two-month period during 2014 -
      2015. A standard forward - backward translation procedure was used to translate
      the English version of the PQOL into Persian. Content, construct, discriminant,
      and criterion validity was assessed. The reliability was evaluated by internal
      consistency and test-retest reliability. RESULTS: The PQOL showed good content
      validity; content validity ratio (CVR) ranged from 0.67 to 1.00 and content
      validity index (CVI) ranged from 0.78 to 1.00. Construct validity evaluation by
      exploratory factor analysis (EFA) led to extraction of six factors from the data.
      Due to the lack of theoretical justification for items' relocation in the
      extracted factors and poor-fitting indices obtained by confirmatory factor
      analysis (CFA), the exploratory model was eliminated, and the original model was
      presented and incorporated into the CFA, indicating an acceptable fit for the
      model (root mean square error of approximation [RMSEA] = 0.038 [0.034; 0.042];
      comparative fit index [CFI] = 0.90; normed fit index [NFI] = 0.80; non-normed fit
      index [NNFI] = 0.90; incremental fit index [IFI] = 0.90). The intergroup
      differences in total and all dimensions of the PQOL, except for social support,
      indicated the discrimination ability of the questionnaire. The questionnaire
      indicated a medium correlation with the short form health survey (SF-12)
      questionnaire (r >= 0.50). Cronbach's alpha coefficient (0.70 - 0.88) indicated a
      good internal consistency, and the intraclass correlation coefficients (0.87 -
      0.92) showed good test - retest reliability. CONCLUSIONS: The findings of this
      study confirmed the validity and reliability of the Iranian version of the PQOL
      questionnaire in Iranian women as a specific measure to evaluate the women's
      quality of life.

PMID- 27703800
TI  - Resilience of Patients With Chronic Physical Diseases: A Systematic Review and
      Meta-Analysis.
AB  - CONTEXT: Resilience can be seen as an adaption to stress, such as that caused by
      health problems or disease, that attenuates the negative effects of stress. The
      present research performed a systematic review and meta-analysis to study
      resilience scores among adults diagnosed with chronic physical diseases. EVIDENCE
      ACQUISITION: Electronic databases, including Persian language (scientific
      information database [SID], IranMedex, Magiran, IranDoc, and Medlib) and English
      language (Google Scholar, Science Direct, PubMed, Pre-Quest, and Scopus), were
      searched. Fifteen articles were found using the keywords disease or chronic
      disease, resilience or resiliency, and illness, either alone or in combination,
      both in Persian and English languages. Data analysis was carried out through meta
      analysis (random-effects model), and heterogeneity was investigated by subgroup
      and meta-regression analyses. The data were analyzed in STAT software (12.0).
      RESULTS: The mean resilience score of the chronic disease patients (n = 3369) was
      74.6 (95% CI: 51.8 - 97.4). In terms of diseases, the mean resilience score of
      cancer patients was 79.6 (95% CI: 48.3 - 111.1), whereas it was 79.6 for
      cardiovascular disease patients (95% CI: 45.8 - 113.3) and 64.6 for patients with
      other diseases (95% CI: 6.6 - 122.7). There was no relationship between the
      resilience of chronic disease patients and the year of the study (P = 0.711) and
      the sample size in the studies (P = 0.351). CONCLUSIONS: The mean resilience
      score of the patients was less than that of healthy individuals. As resilience
      can be acquired at any stage of life, irrespective of age and disease status,
      there is a need for training to improve resilience among patients through
      educational programs.

PMID- 27703801
TI  - Trans-4 Portal as a New Portal for Accessing the Lunate in Wrist Arthroscopy: a
      Cadaveric Study.
AB  - BACKGROUND: Evolving wrist arthroscopy requires creating new portals, and
      creating portals reciprocally leads to increased indications for arthroscopic
      wrist procedures. To facilitate access to the lunate bone and fossa for new
      arthroscopic procedures, a new portal was used. This is a cadaveric study of this
      portal. OBJECTIVES: In this cadaveric study, we evaluated a portal in wrist
      arthroscopy for procedures involving the lunate bone and lunate fossa. MATERIALS
      AND METHODS: Seventeen wrists from 10 fresh cadavers were included in this study.
      After diagnostic arthroscopy, a portal (Trans-4) was made through the fourth
      extensor compartment, exactly along the lunate's long axis under direct
      visualization from the 3-4 portal. Strand retractors were used to protect the
      extensor tendons and posterior capsule. Lunate bone core decompression and
      osteoscopy were done through the portal. At the end of the procedure, the
      position of the decompression hole in the lunate and any possible injury to the
      extensor tendons, distal radius cartilage, lunate cartilage, and perilunate
      ligaments were investigated. RESULTS: Lunate bone decompression was performed
      successfully in all cases using the trans-4 portal. In 15 wrists, the lunate hole
      was located in the middle third. In the other two wrists, it was located slightly
      radial in one case and slightly on the ulnar side in the other case. There was no
      cortical penetration during decompression, and no extensor tendon, superficial
      nerve branches, or peri-lunate ligament injuries were observed. CONCLUSIONS: The
      trans-4 portal could be a safe working portal in wrist arthroscopy that enables
      access to the lunate bone and lunate fossa.

PMID- 27703802
TI  - Treatment of Distal Radius Fracture Nonunion With Posterior Interosseous Bone
      Flap.
AB  - BACKGROUND: Nonunion of distal radius fractures is disabling. Treatment is
      difficult and the results are not predictable. However, posterior interosseous
      bone flap (PIBF) has been successful in treating forearm nonunion. OBJECTIVES: To
      treat distal radius fracture nonunion with PIBF as a new procedure. PATIENTS AND
      METHODS: This prospective non-randomized cohort study was performed at two
      hospitals in Tehran between January 2011 and September 2015. PIBFs were applied
      in nine patients (10 nonunions) with a mean age of 55 years. Union success rate,
      grip strength, wrist range of motion, and forearm rotation were then evaluated.
      RESULTS: Although four of the patients had a history of infection, all
      participants achieved fracture union at a mean time of 3.8 months. Grip strength
      improved by 12.4 kg. There was also 36 degrees  improvement in wrist flexion, 20
      degrees  improvement in wrist extension, 60 degrees  improvement in forearm
      supination, and 46 degrees  improvement in forearm pronation. The range of motion
      and grip strength improvements were significant. CONCLUSIONS: Pedicled PIBF is a
      new option for treating distal radius fracture nonunion. The results are
      predictable in achieving union and good function, and this technique can be
      successfully used in cases with extensive soft-tissue damage or infection.

PMID- 27703803
TI  - Reliability of Using Retinal Vascular Fractal Dimension as a Biomarker in the
      Diabetic Retinopathy Detection.
AB  - The retinal fractal dimension (FD) is a measure of vasculature branching pattern
      complexity. FD has been considered as a potential biomarker for the detection of
      several diseases like diabetes and hypertension. However, conflicting findings
      were found in the reported literature regarding the association between this
      biomarker and diseases. In this paper, we examine the stability of the FD
      measurement with respect to (1) different vessel annotations obtained from human
      observers, (2) automatic segmentation methods, (3) various regions of interest,
      (4) accuracy of vessel segmentation methods, and (5) different imaging
      modalities. Our results demonstrate that the relative errors for the measurement
      of FD are significant and FD varies considerably according to the image quality,
      modality, and the technique used for measuring it. Automated and semiautomated
      methods for the measurement of FD are not stable enough, which makes FD a
      deceptive biomarker in quantitative clinical applications.

PMID- 27703804
TI  - Corrigendum to "A Review of Collagen Cross-Linking in Cornea and Sclera".
AB  - [This corrects the article DOI: 10.1155/2015/289467.].

PMID- 27703806
TI  - Schoolchildren with Learning Difficulties Have Low Iron Status and High Anemia
      Prevalence.
AB  - Background. In developing countries there is high prevalence of iron deficiency
      anemia, which reduces cognitive performance, work performance, and endurance; it
      also causes learning difficulties and negative impact on development for infant
      population. Methods. The study concerns a case-control study; data was collected
      from an appropriate sample consisting of schoolchildren aged 8 years. The sample
      was divided into two subgroups: those with deficient initial reading skills
      (DIRS) (case) and those without (control). Blood samples were taken to analyze
      hemoglobin and serum ferritin levels. These results were then used to compare the
      two groups with Student's t-test. Association between DIRS and anemia was
      analyzed using odds ratio (OR). Results. Hemoglobin and serum ferritin levels of
      schoolchildren with DIRS were statistically lower when compared to those without,
      hemoglobin p = 0.02 and serum ferritin p = 0.04. DIRS was statistically
      associated with a risk of anemia with a weighted OR of 1.62. Conclusions. In this
      study, schoolchildren with DIRS had lower hemoglobin and serum ferritin levels
      when compared to those without.

PMID- 27703805
TI  - Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and
      Review of the Literature.
AB  - The aetiology of obesity has been attributed to several factors (environmental,
      dietary, lifestyle, host, and genetic factors); however none of these fully
      explain the increase in the prevalence of obesity worldwide. Gut microbiota
      located at the interface of host and environment in the gut are a new area of
      research being explored to explain the excess accumulation of energy in obese
      individuals and may be a potential target for therapeutic manipulation to reduce
      host energy storage. Several mechanisms have been suggested to explain the role
      of gut microbiota in the aetiology of obesity such as short chain fatty acid
      production, stimulation of hormones, chronic low-grade inflammation, lipoprotein
      and bile acid metabolism, and increased endocannabinoid receptor system tone.
      However, evidence from animal and human studies clearly indicates controversies
      in determining the cause or effect relationship between the gut microbiota and
      obesity. Metagenomics based studies indicate that functionality rather than the
      composition of gut microbiota may be important. Further mechanistic studies
      controlling for environmental and epigenetic factors are therefore required to
      help unravel obesity pathogenesis.

PMID- 27703807
TI  - The Development of Intensive Care Unit Acquired Hypernatremia Is Not Explained by
      Sodium Overload or Water Deficit: A Retrospective Cohort Study on Water Balance
      and Sodium Handling.
AB  - Background. ICU acquired hypernatremia (IAH, serum sodium concentration (sNa) >=
      143 mmol/L) is mainly considered iatrogenic, induced by sodium overload and water
      deficit. Main goal of the current paper was to answer the following questions:
      Can the development of IAH indeed be explained by sodium intake and water
      balance? Or can it be explained by renal cation excretion? Methods. Two
      retrospective studies were conducted: a balance study in 97 ICU patients with and
      without IAH and a survey on renal cation excretion in 115 patients with IAH.
      Results. Sodium intake within the first 48 hours of ICU admission was 12.5 [9.3
      17.5] g in patients without IAH (n = 50) and 15.8 [9-21.9] g in patients with IAH
      (n = 47), p = 0.13. Fluid balance was 2.3 [1-3.7] L and 2.5 [0.8-4.2] L,
      respectively, p = 0.77. Urine cation excretion (urine Na + K) was < sNa in 99 out
      of 115 patients with IAH. Severity of illness was the only independent variable
      predicting development of IAH and low cation excretion, respectively. Conclusion.
      IAH is not explained by sodium intake or fluid balance. Patients with IAH are
      characterized by low urine cation excretion, despite positive fluid balances. The
      current paradigm does not seem to explain IAH to the full extent and warrants
      further studies on sodium handling in ICU patients.

PMID- 27703809
TI  - Hippocampography Guides Consistent Mesial Resections in Neocortical Temporal Lobe
      Epilepsy.
AB  - Background. The optimal surgery in lesional neocortical temporal lobe epilepsy is
      unknown. Hippocampal electrocorticography maximizes seizure freedom by
      identifying normal-appearing epileptogenic tissue for resection and minimizes
      neuropsychological deficit by limiting resection to demonstrably epileptogenic
      tissue. We examined whether standardized hippocampal electrocorticography
      (hippocampography) guides resection for more consistent hippocampectomy than
      unguided resection in conventional electrocorticography focused on the lesion.
      Methods. Retrospective chart reviews any kind of electrocorticography (including
      hippocampography) as part of combined lesionectomy, anterolateral temporal
      lobectomy, and hippocampectomy over 8 years . Patients were divided into mesial
      (i.e., hippocampography) and lateral electrocorticography groups. Primary outcome
      was deviation from mean hippocampectomy length. Results. Of 26 patients, fourteen
      underwent hippocampography-guided mesial temporal resection. Hippocampography was
      associated with 2.6 times more consistent resection. The range of hippocampal
      resection was 0.7 cm in the mesial group and 1.8 cm in the lateral group (p =
      0.01). 86% of mesial group versus 42% of lateral group patients achieved seizure
      freedom (p = 0.02). Conclusions. By rationally tailoring excision to demonstrably
      epileptogenic tissue, hippocampography significantly reduces resection
      variability for more consistent hippocampectomy than unguided resection in
      conventional electrocorticography. More consistent hippocampal resection may
      avoid overresection, which poses greater neuropsychological risk, and
      underresection, which jeopardizes postoperative seizure freedom.

PMID- 27703808
TI  - Depressive Symptoms among Latino Sexual Minority Men and Latina Transgender Women
      in a New Settlement State: The Role of Perceived Discrimination.
AB  - Background. Little is known about the role of discrimination on depression among
      Latino sexual and gender identity minorities. This manuscript examined the
      relationship between ethnic/racial discrimination and sexual discrimination on
      clinically significant depressive symptoms among Latino sexual minority men
      (i.e., gay and bisexual men and other men who have sex with men) and Latina
      transgender women. Methods. A community-based participatory research partnership
      recruited participants (N = 186; 80.6% cisgender men) in North Carolina to a
      social network-based HIV intervention. Using baseline data, we quantified the
      amount of perceived discrimination and conducted mixed-effects logistic
      regression analyses to examine correlates of clinically significant depressive
      symptoms. Results. A high percentage of participants reported ethnic/racial
      discrimination (73.7%) and sexual discrimination (53.8%). In the multivariable
      models, ethnic/racial discrimination, sexual discrimination, masculinity,
      fatalism, and social support were significantly associated with clinically
      significant depressive symptoms. Discussion. Improving mental health requires
      multilevel interventions that address pertinent individual, interpersonal, and
      system level factors.

PMID- 27703810
TI  - Relatives to Critically Ill Patients Have No Sense of Coherence: A Quality
      Improvement Article Using Mixed Methods.
AB  - Aims and Objective. To investigate the relatives' satisfaction and involvement on
      a general surgery ward regarding the critically ill patient. Introduction.
      Relatives to critically ill patients are affected both physically and mentally
      during the hospitalization of a family member. Research has shown that relatives
      do not always receive the attention they need from health professionals. There is
      a lack of studies that focus on relatives' satisfaction and involvement during
      their family members' hospitalization. Design. A mixed methods design was chosen.
      Methods. A quantitative study was conducted with 27 relatives to critically ill
      patients. All participated in a questionnaire and out of the 27 relatives, six
      participated in qualitative in-depth interviews. Results. The questionnaire
      revealed that relatives were dissatisfied with care and involvement. For further
      exploration of the dissatisfaction, a qualitative approach was used and the in
      depth interviews revealed three themes: lack of continuity and structure,
      responsibility of coordination, and relatives feeling left on their own with no
      guiding and support. Conclusion. Health professionals' key role in relation to
      relatives must be guidance and support. Thereby, relatives can gain a sense of
      coherence during the hospitalization of a critically ill patient, which can lead
      to a greater satisfaction and thereby better support for the patient.

PMID- 27703811
TI  - Comment on "Cost-Saving Early Diagnosis of Functional Pain in Nonmalignant Pain:
      A Noninferiority Study of Diagnostic Accuracy".

PMID- 27703812
TI  - Assessment and Predicting Factors of Repeated Brain Computed Tomography in
      Traumatic Brain Injury Patients for Risk-Stratified Care Management: A 5-Year
      Retrospective Study.
AB  - Background and Objective. To determine the value of repeated brain CT in TBI
      cases for risk-stratified care management (RSCM) and to identify predicting
      factors which will change the neurosurgical management after repeated brain CTs.
      Methods. A 5-year retrospective study from January 2009 to August 2013 was
      conducted. The primary outcome was the value of repeated brain CT in TBI cases.
      The secondary outcome is to identify predicting factors which will change the
      neurosurgical management after repeated brain CTs. Results. There were 145
      consecutive patients with TBI and repeated brain CT after initial abnormal brain
      CT. Forty-two percent of all cases (N = 61) revealed the progression of
      intracranial hemorrhage after repeated brain CT. In all 145 consecutive patients,
      67.6% of cases (N = 98) were categorized as mild TBI. For mild head injury, 8.2%
      of cases (N = 8) had undergone neurosurgical management after repeated brain CT.
      Only 1 from 74 mild TBI patients with repeated brain CT had neurosurgical
      intervention. Clopidogrel and midline shift more than 2 mm on initial brain CT
      were significant predicting factors to indicate the neurosurgical management in
      mild TBI cases. Conclusion. Routine repeated brain CT for RSCM had no clinical
      benefit in mild TBI cases.

PMID- 27703813
TI  - Sex Differences in Severity, Social Functioning, Adherence to Treatment, and
      Cognition of Adolescents with Schizophrenia.
AB  - Background. Previous studies have reported sex differences in the clinical
      presentation and outcome of adult patients with schizophrenia; the aim of present
      study was to compare the clinical characteristics, social functioning, adherence
      to treatment, and cognition of adolescents with this diagnosis in a six-month
      followup. Methods. A total of 87 adolescents with a DSM-IV diagnosis of
      schizophrenia or schizophreniform disorder were evaluated with the Positive and
      Negative Symptoms Scale (PANSS), the Matrics Consensus Cognitive Battery (MCCB),
      Personal and Social Performance Scale (PSP), and the Rating of Medication
      Influences (ROMI). Results. Both groups showed a similar improvement in all PANSS
      factors and in the PSP scores during the followup. Males better adhered to
      treatment. Females displayed better results in the area of social cognition (F =
      6.3, df = 2,52, and p = 0.003) and attention/vigilance (F = 8.3, df = 2,51, and p
      = 0.001). Conclusions. Male and female adolescents showed similar clinical
      presentation and functioning but a different pattern of cognitive improvement and
      adherence to treatment. This trial is registered with Clinicaltrials.gov
      II3/02/0811.?.

PMID- 27703814
TI  - Cloning, Sequencing, and the Expression of the Elusive Sarcomeric TPM4alpha
      Isoform in Humans.
AB  - In mammals, tropomyosin is encoded by four known TPM genes (TPM1, TPM2, TPM3, and
      TPM4) each of which can generate a number of TPM isoforms via alternative
      splicing and/or using alternate promoters. In humans, the sarcomeric isoform(s)
      of each of the TPM genes, except for the TPM4, have been known for a long time.
      Recently, on the basis of computational analyses of the human genome sequence,
      the predicted sequence of TPM4alpha has been posted in GenBank. We designed
      primer-pairs for RT-PCR and showed the expression of the transcripts of TPM4alpha
      and a novel isoform TPM4delta in human heart and skeletal muscle. qRT-PCR shows
      that the relative expression of TPM4alpha and TPM4delta is higher in human
      cardiac muscle. Western blot analyses using CH1 monoclonal antibodies show the
      absence of the expression of TPM4delta protein (~28 kDa) in human heart muscle.
      2D western blot analyses with the same antibody show the expression of at least
      nine distinct tropomyosin molecules with a mass ~32 kD and above in adult heart.
      By Mass spectrometry, we determined the amino acid sequences of the extracted
      proteins from these spots. Spot "G" reveals the putative expression of TPM4alpha
      along with TPM1alpha protein in human adult heart.

PMID- 27703815
TI  - Corrigendum to "Closely Spaced MEG Source Localization and Functional
      Connectivity Analysis Using a New Prewhitening Invariance of Noise Space
      Algorithm".
AB  - [This corrects the article DOI: 10.1155/2016/4890497.].

PMID- 27703816
TI  - Sudden Appearance of Indurated Erythematous Plaques on a Man's Face.
AB  - Rosacea fulminans (RF), previously known as pyoderma faciale, is a rare
      presentation of rosacea mostly seen in young women. RF is seen very rarely in
      men. We present below a case of a fifty-year-old male who presented with RF and
      was successfully treated with a combination of corticosteroids and isotretinoin.

PMID- 27703817
TI  - Conservative Treatment of Carpometacarpal Dislocation of the Three Last Fingers.
AB  - Posterior carpometacarpal (CMC) dislocation is a rare condition. Treatment is
      usually surgical though no strict consensus can be found upon literature review.
      If diagnosed early and no associated fractures are found, CMC dislocation could
      benefit from conservative treatment comprising closed reduction and splint
      immobilisation. We report the case of a 26-year-old man diagnosed with a
      posterior dislocation of the third, fourth, and fifth CMC joints after a fall of
      1.5 meters, treated by external reduction under procedural sedation and
      immobilisation with a cast for 6 weeks. Evolution was excellent with no relapse
      observed during follow-up. Our aim is to increase physician awareness of CMC
      dislocation so that they seek this injury in the emergency department.
      Unrecognised CMC dislocation can lead to neurovascular injuries as well as
      chronic instability and early articular degeneration.

PMID- 27703819
TI  - A Case of Mycobacterium riyadhense in an Acquired Immune Deficiency Syndrome
      (AIDS) Patient with a Suspected Paradoxical Response to Antituberculosis Therapy.
AB  - A 30-year-old male patient with acquired immune deficiency syndrome (AIDS) on
      highly active antiretroviral therapy (HAART) presented with clinical picture
      suggestive of pulmonary tuberculosis. He was commenced on antituberculosis
      therapy (ATT) with signs of improvement. Then he developed cervical lymph node
      abscess which was drained. Steroid was started for presumed paradoxical response
      to ATT which results in clinical regression. The culture result revealed
      Mycobacterium riyadhense. This report addresses the rarity of this bacteria in
      medical literature. It reviews clinical presentations and medical treatment
      particularly in the setting of coinfections.

PMID- 27703818
TI  - Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia
      on Ibrutinib.
AB  - Cryptococcus is a unique environmental fungus that can cause disease most often
      in immunocompromised individuals with defective cell-mediated immunity. Chronic
      lymphocytic leukemia (CLL) is not known to be a risk factor for cryptococcal
      disease although cases have been described mainly in patients treated with agents
      that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for
      treatment of CLL, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. It
      acts by inhibiting Bruton's tyrosine kinase, a kinase downstream of the B-cell
      receptor critical for B-cell survival and proliferation. Ibrutinib use has not
      been associated previously with cryptococcal disease. However, recent evidence
      suggested that treatments aimed at blocking the function of Bruton's tyrosine
      kinase could pose a higher risk for cryptococcal infection in a mice model. Here,
      we report the first case of disseminated cryptococcal disease in a patient with
      CLL treated with ibrutinib. When evaluating possible infection in CLL patients
      receiving ibrutinib, cryptococcal disease, which could be life threatening if
      overlooked, could be considered.

PMID- 27703820
TI  - Therapeutic Drug Monitoring of Meropenem in Neonate with Necrotizing
      Enterocolitis: A Challenge.
AB  - Necrotizing enterocolitis (NEC) continues to be a major cause of neonatal
      morbidity and mortality. We describe the added value of therapeutic drug
      monitoring by presenting the case of a preterm infant with severe NEC treated
      with meropenem. Dosing strategy will achieve adequate patient outcome when
      treating pathogens with elevated MIC. As safe as meropenem is, there are not
      enough data for 40 mg/kg, every 8 h infused over 4 h; accordingly, strict
      monitoring of blood levels is mandatory. Based on our findings, a 4 h prolonged
      infusion of 40 mg/kg meropenem, every 8 h, will achieve an adequate patient
      outcome.

PMID- 27703821
TI  - External Otitis: An Unusual Presentation in Neonates.
AB  - Acute otitis externa (AOE) is an infection of the external auditory canal, the
      auricle, and the outer surface of the tympanic membrane. Although AOE is one of
      the most common otologic conditions encountered in pediatric population, it is
      known to primarily affect children older than 2 years. We report a case of AOE
      caused by Staphylococcus aureus in a 23-day-old neonate. A 23-day-old female
      infant presented to our neonatology clinic with irritability and discharge from
      the right ear. There were yellow otorrhea, mild erythema, and edema of right
      external ear canal. There was no sign of otitis media on otoscopy. The results of
      laboratory tests were insignificant. The discharge culture grew colonies of
      methicillin-sensitive Staphylococcus aureus. After 48 hours of treatment with
      intravenous cloxacillin, significant improvement was observed. The present case
      highlights an unusual presentation of staphylococcal infection in a neonate. This
      is the first case of methicillin-sensitive Staphylococcus aureus otitis externa
      in an immunocompetent newborn.

PMID- 27703822
TI  - Interstitial Nephritis in a Patient with Inflammatory Bowel Disease.
AB  - Tubulointerstitial nephritis in patients with inflammatory bowel disease has been
      linked to the use of 5-ASA derivatives. Various aspects of this theory have been
      challenged with a potential role for the underlying autoimmune disorder. Steroids
      are the mainstay of treatment and mycophenolate mofetil might be an effective
      alternative. We report a patient who responded well to mycophenolate despite
      continuing mesalamine, the suspected offending agent.

PMID- 27703823
TI  - A Case of West Nile Encephalitis That Develops into a Disease of Deep White
      Matter on MRI over a Two-Week Span.
AB  - We present a case of serologically proved West Nile encephalitis. This patient
      had a normal MRI on admission. Given that the patient's clinical picture had
      worsened during her admission, a repeat MRI was performed, which demonstrated
      diffuse disease in the deep white matter of the brain. This is a case of West
      Nice encephalitis presenting as a disease of deep white matter that developed
      over a two-week span.

PMID- 27703824
TI  - Spontaneous Recurrent Hemarthrosis of the Knee: A Report of Two Cases with a
      Source of Bleeding Detected during Arthroscopic Surgery of the Knee Joint.
AB  - We report two cases of the spontaneous recurrent hemarthrosis of the knee. In
      these cases lateral meniscus was severely torn and a small tubular soft tissue
      with pulsation was identified on the synovium in the posterolateral corner during
      arthroscopic surgery of the knee joint. Gentle grasping of this tissue by forceps
      led to pulsating bleeding, which stopped by electrocoagulation. This soft tissue
      was considered a source of bleeding, since no recurrence of hemarthrosis was
      observed for more than four years after surgery. It was highly probable that this
      soft tissue was the ruptured end of the lateral inferior genicular artery or its
      branch. This case report strongly supports the theory that the bleeding from the
      peripheral arteries of the posterior portion of the lateral meniscus is the cause
      of spontaneous recurrent hemarthrosis of the knee.

PMID- 27703825
TI  - Solitary Spinal Epidural Metastasis from Gastric Cancer.
AB  - Solitary epidural space metastasis of a malignant tumor is rare. We encountered a
      79-year-old male patient with solitary metastatic epidural tumor who developed
      paraplegia and dysuria. The patient had undergone total gastrectomy for gastric
      cancer followed by chemotherapy 8 months priorly. The whole body was examined for
      suspected metastatic spinal tumor, but no metastases of the spine or important
      organs were observed, and a solitary mass was present in the thoracic spinal
      epidural space. The mass was excised for diagnosis and treatment and was
      histopathologically diagnosed as metastasis from gastric cancer. No solitary
      metastatic epidural tumor from gastric cancer has been reported in English. Among
      the Japanese, 3 cases have been reported, in which the outcome was poor in all
      cases and no definite diagnosis could be made before surgery in any case. Our
      patient developed concomitant pneumonia after surgery and died shortly after the
      surgery. When a patient has a past medical history of malignant tumor, the
      possibility of a solitary metastatic tumor in the epidural space should be
      considered.

PMID- 27703826
TI  - Entrapment of Common Peroneal Nerve by Surgical Suture following Distal Biceps
      Femoris Tendon Repair.
AB  - We describe entrapment of the common peroneal nerve by a suture after surgical
      repair of the distal biceps femoris tendon. Complete rupture of the distal biceps
      femoris tendon of a 16-year-old male athlete was surgically repaired.
      Postoperative common peroneal nerve palsy was evident, but conservative treatment
      did not cause any neurological improvement. Reexploration revealed that the
      common peroneal nerve was entrapped by the surgical suture. Complete removal of
      the suture and external neurolysis significantly improved the palsy. The common
      peroneal nerve is prone to damage as a result of its close proximity to the
      biceps femoris tendon and it should be identified during surgical repair of a
      ruptured distal biceps femoris tendon.

PMID- 27703828
TI  - Right Atrial Appendage Aneurysm in a Newborn Diagnosed with Fetal
      Echocardiography.
AB  - Right atrial appendage aneurysm is a very rare condition which can be
      asymptomatic or can cause arrhythmia or life-threatening thromboembolism. We
      report a case of newborn with right atrial appendage aneurysm who was diagnosed
      with fetal echocardiography. Anticoagulant therapy was applied to prevent
      thromboembolism and he is still going on follow-up without any complaint.

PMID- 27703827
TI  - Chronic Invasive Nongranulomatous Fungal Rhinosinusitis in Immunocompetent
      Individuals.
AB  - Chronic invasive nongranulomatous fungal rhinosinusitis is a well-described but
      uncommon type of fungal rhinosinusitis (FRS). While the prevalence of chronic FRS
      is 0.11% in healthy individuals, only 1.3% of them are in nongranulomatous
      invasive nature. The majority of the cases in the literature have been reported
      from developing countries mostly located in the tropical regions, as typically
      occurring in the background of diabetes mellitus or corticosteroid treatment. The
      current paper reports four consecutive cases, who were diagnosed within a short
      period of six months at a single center of a country located outside the tropical
      climate zone. None of the patients had a comorbid disease that may cause immune
      suppression or a history of drug use. The only risk factor that may have a role
      in development of chronic invasive nongranulomatous FRS was that all of our
      patients were people working in greenhouse farming. Three cases underwent
      endoscopic sinus surgery, and one case underwent surgery with both endoscopic and
      external approaches. Systemic antifungal therapy was initiated in all cases in
      the postoperative period with voriconazole 200 mg orally twice a day. All
      patients achieved a complete clinical remission. Chronic invasive
      nongranulomatous FRS should be kept in mind in the presence of long-standing
      nonspecific sinonasal symptoms in immunocompetent individuals, particularly with
      a history of working in greenhouse farming.

PMID- 27703829
TI  - Development of Tinnitus at a Low Dose of Sertraline: Clinical Course and Proposed
      Mechanisms.
AB  - Introduction. Serotonin is involved in filtering of auditory stimuli. Cochlear
      input is processed through complex interactions between serotonergic,
      glutamatergic, and GABAergic neurotransmitter systems. Options for treatment of
      tinnitus include selective serotonin reuptake inhibitors (SSRIs); however in rare
      instances this symptom may occur as a side effect of this class of medications.
      Case Presentation. A 50-year-old woman developed bilateral tinnitus after several
      weeks of being treated with sertraline 50 mg. She had been on a long-standing
      daily dose of aspirin 325 mg which had been discontinued shortly before starting
      sertraline. Medical work-up was negative for her symptom. Shortly after
      discontinuation of the medication, her tinnitus subsided completely. Discussion.
      Tinnitus is a rare side effect of sertraline and may be related to particular
      distribution of serotonin receptor subtypes within the auditory system, and
      serotonergic agents may reinforce or desensitize the activity of different
      receptors. Also, there may be a priming effect of salicylate agents on the
      auditory system, predisposing particular patients to be more sensitive to how
      auditory stimuli are processed.

PMID- 27703830
TI  - A Curious Case of Proximal Muscle Weakness with Eosinophilic Polymyositis.
AB  - Eosinophilic polymyositis (EPM) is part of a rare disorder, eosinophilic
      myopathies (EM), which is a form of polymyositis characterized by the presence of
      eosinophils in muscle biopsy sections and occasionally blood eosinophilia.
      Herein, we are presenting an interesting case of eosinophilic polymyositis
      presenting with muscle pain with no other organ systems involved.

PMID- 27703831
TI  - Spontaneous Septic Arthritis of Pubic Symphysis in an Elite Athlete.
AB  - Septic arthritis of the pubic symphysis is a potentially severe disease. Athletes
      are at risk of this form of spontaneous arthritis, as inflammation of the pubic
      bone due to muscular stress is relatively common. Oedema due to inflammation
      might predispose to infection through bacteraemia or local bacterial
      translocation. Suspicion should be raised when an athlete complains of groin pain
      and has signs of infection (i.e., fever, elevated white blood cell count, and
      elevated C-reactive protein). Diagnosis is made by imaging showing signs of
      inflammation combined with positive (blood) cultures. Broad spectrum antibiotics
      should be started upon suspicion and adjusted according to cultures. An abscess
      causing clinical deterioration under antibiotic treatment is an indication for
      invasive intervention (i.e., surgical or image-guided drainage). This is the
      first case of spontaneous septic arthritis of the pubic symphysis in an athlete
      requiring surgical and additional image-guided drainage.

PMID- 27703833
TI  - Intraluminal Bowel Erosion: A Rare Complication of Retained Gallstones after
      Cholecystectomy.
AB  - Laparoscopic cholecystectomy for acute cholecystitis and cholelithiasis is one of
      the most common operations performed in the United States. Inadvertent
      perforation and spillage of gallbladder contents are not uncommon. The potential
      impact of subsequent retained gallstones is understated. We present the case of
      an intraperitoneal gallstone retained from a previous cholecystectomy eroding
      into the bowel and leading to intraluminal mechanical bowel obstruction requiring
      operative intervention. This case illustrates the potential risks of retained
      gallstones and reinforces the need to diligently collect any dropped stones at
      the time of initial operation.

PMID- 27703834
TI  - Endovascular Aneurysm Repair in HIV Patients with Ruptured Abdominal Aneurysm and
      Low CD4.
AB  - We report two HIV infected patients with ruptured abdominal aneurysm by using
      endovascular aneurysm repair (EVAR) technique. A 59-year-old Thai man had a
      ruptured abdominal aortic aneurysm and a 57-year-old man had a ruptured iliac
      artery aneurysm. Both patients had a CD4 level below 200 MU/L indicating a low
      immune status at admission. They were treated by EVAR. Neither patient had any
      complications in 3 months postoperatively. EVAR may have a role in HIV patients
      with ruptured abdominal aneurysm together with very low immunity.

PMID- 27703832
TI  - Wandering Spleen and Organoaxial Gastric Volvulus after Morgagni Hernia Repair: A
      Case Report and Review of the Literature.
AB  - Wandering spleen and gastric volvulus are two rare entities that have been
      described in association with congenital diaphragmatic hernia. The diagnosis is
      difficult and any delay can result in ischemia and necrosis of both organs. We
      present a case of a 13-year-old girl, previously operated on for anterior
      diaphragmatic hernia and intrathoracic gastric volvulus, that presented to our
      service for a subdiaphragmatic gastric volvulus recurrence associated with a
      wandering spleen. In this report we reviewed the literature, analyzing the
      clinical presentation, diagnostic assessment, and treatment options of both
      conditions, in particular in the case associated with diaphragmatic hernia.

PMID- 27703835
TI  - Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection.
AB  - The mortality in Strongyloides hyperinfection syndrome (SHS) is alarmingly high.
      This is particularly common in bone marrow, renal, and other solid organ
      transplant (SOT) patients, where figures may reach up to 50-85%.
      Immunosuppressives, principally corticosteroids, are the primary triggering
      factor. In general, the clinical features of Strongyloides stercoralis
      hyperinfection are nonspecific; therefore, a high index of suspicion is required
      for early diagnosis and starting appropriate therapy. Although recurrent Gram
      negative sepsis and meningitis have been previously reported, the combination of
      both cytomegalovirus (CMV) and strongyloidiasis had rarely been associated. We
      here describe a patient who survived SHS with recurrent Escherichia coli (E.
      coli) urosepsis and CMV infection.

PMID- 27703836
TI  - A Prolapsed Cecoureterocele in an Adult Treated Conservatively: Highly Rare, but
      Existent.
AB  - Ectopic ureteroceles are one of the most common human urinary tract anomalies.
      They tend to be recognized and treated in early childhood, especially when they
      have prolapsed. In most cases surgical therapy is inevitable. In this case
      report, however, we present the unusual case of a 26-year-old woman suffering
      from a prolapsed cecoureterocele without any known history of an ectopic
      ureterocele so far. She was successfully treated without the need for a surgical
      procedure.

PMID- 27703838
TI  - Erratum: Pit- and trench-forming osteoclasts: a distinction that matters.
AB  - [This corrects the article DOI: 10.1038/boneres.2015.32.].

PMID- 27703837
TI  - New Biomedical Technologies and Strategies for Prevention of HIV and Other
      Sexually Transmitted Infections.
AB  - Sexually transmitted infections remain to be of public health concern in many
      developing countries. Their control is important, considering the high incidence
      of acute infections, complications and sequelae, and their socioeconomic impact.
      This article discusses the new biomedical technologies and strategies for the
      prevention of HIV and other sexually transmitted infections.

PMID- 27703840
TI  - Continuum beliefs in the stigma process regarding persons with schizophrenia and
      depression: results of path analyses.
AB  - BACKGROUND: Individuals with mental illness often experience stigmatization and
      encounter stereotypes such as being dangerous or unpredictable. To further
      improve measures against psychiatric stigma, it is of importance to understand
      its components. In this study, we attend to the step of separation between "us"
      and "them" in the stigma process as conceptualized by Link and Phelan. In using
      the belief in continuity of mental illness symptoms as a proxy for separation, we
      explore its associations with stereotypes, emotional responses and desire for
      social distance in the stigma process. METHODS: Analyses are based on a
      representative survey in Germany. Vignettes with symptoms suggestive of
      schizophrenia (n = 1,338) or depression (n = 1,316) were presented to the
      respondents, followed by questions on continuum belief, stereotypes, emotional
      reactions and desire for social distance. To examine the relationship between
      these items, path models were computed. RESULTS: Respondents who endorsed the
      continuum belief tended to show greater prosocial reactions (schizophrenia: 0.07;
      p < 0.001, depression: 0.09; p < 0.001) and less desire for social distance
      (schizophrenia: -0.13; p < 0.001, depression: -0.14; p < 0.001) toward a person
      with mental illness. In both cases, agreement with the stereotypes of
      unpredictability and dangerousness was positively associated with feelings of
      anger and fear as well as desire for social distance. There were no statistically
      significant relations between stereotypes and continuum beliefs. DISCUSSION:
      Assumptions regarding continuum beliefs in the stigma process were only partially
      confirmed. However, there were associations of continuum beliefs with less
      stigmatizing attitudes toward persons affected by either schizophrenia or
      depression. Including information on continuity of symptoms, and thus oppose
      perceived separation, could prove helpful in future anti-stigma campaigns.

PMID- 27703841
TI  - Extremely low genetic variability within and among locations of the greenfish
      holothurian Stichopus chloronotus Brandt, 1835 in Okinawa, Japan.
AB  - The greenfish sea cucumber Stichopus chloronotus is an economically and
      ecologically important sea cucumber species throughout its range. This species is
      widely distributed, inhabiting coral reefs of the Indo-Pacific Ocean. Our study
      evaluated population genetic structure and levels of genetic diversity in
      southern Japan. A total of 180 individuals were collected from eight locations
      from Okinawa and Okinoerabu Islands and sequenced using mitochondrial 16S
      ribosomal DNA (16S) and nuclear histone H3 (H3) gene. Only three 16S haplotypes
      were detected (518 bp) with haplotype diversity ranging from 0 to 0.56 and
      nucleotide diversity from 0 to 0.1%. H3 showed no variation among the studied
      locations. It is plausible that such results could be due to a shift to asexual
      reproduction. Additionally, the presence of the species on the east coast of
      Okinawa could only be detected in one location and all individuals consisted of a
      single haplotype. Genetic differences between the east and west coasts of Okinawa
      have been noticed in other coral reef organisms, and attributed to either
      ecological or biogeographical historical differences between the coasts due to
      differing levels of isolation during Pleistocene ice ages. Results from the
      present study should inform management and conservation policies of S.
      chloronotus in southern Japan.

PMID- 27703842
TI  - RBioplot: an easy-to-use R pipeline for automated statistical analysis and data
      visualization in molecular biology and biochemistry.
AB  - BACKGROUND: Statistical analysis and data visualization are two crucial aspects
      in molecular biology and biology. For analyses that compare one dependent
      variable between standard (e.g., control) and one or multiple independent
      variables, a comprehensive yet highly streamlined solution is valuable. The
      computer programming language R is a popular platform for researchers to develop
      tools that are tailored specifically for their research needs. Here we present an
      R package RBioplot that takes raw input data for automated statistical analysis
      and plotting, highly compatible with various molecular biology and biochemistry
      lab techniques, such as, but not limited to, western blotting, PCR, and enzyme
      activity assays. METHOD: The package is built based on workflows operating on a
      simple raw data layout, with minimum user input or data manipulation required.
      The package is distributed through GitHub, which can be easily installed through
      one single-line R command. A detailed installation guide is available at
      http://kenstoreylab.com/?page_id=2448. Users can also download demo datasets from
      the same website. RESULTS AND DISCUSSION: By integrating selected functions from
      existing statistical and data visualization packages with extensive
      customization, RBioplot features both statistical analysis and data visualization
      functionalities. Key properties of RBioplot include: -Fully automated and
      comprehensive statistical analysis, including normality test, equal variance
      test, Student's t-test and ANOVA (with post-hoc tests);-Fully automated
      histogram, heatmap and joint-point curve plotting modules;-Detailed output files
      for statistical analysis, data manipulation and high quality graphs;-Axis range
      finding and user customizable tick settings;-High user-customizability.

PMID- 27703839
TI  - Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O
      linked N-acetylglucosamine transferase in oncogenesis and cancer progression.
AB  - The alteration of glucose metabolism, through increased uptake of glucose and
      glutamine addiction, is essential to cancer cell growth and invasion. Increased
      flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives
      increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to
      cancer progression by regulating key oncogenes. However, the association between
      hyper-O-GlcNAcylation and activation of these oncogenes remains poorly
      characterized. Here, we implement a qualitative modeling framework to analyze the
      role of the Biological Regulatory Network in HBP activation and its potential
      effects on key oncogenes. Experimental observations are encoded in a temporal
      language format and model checking is applied to infer the model parameters and
      qualitative model construction. Using this model, we discover step-wise genetic
      alterations that promote cancer development and invasion due to an increase in
      glycolytic flux, and reveal critical trajectories involved in cancer progression.
      We compute delay constraints to reveal important associations between the
      production and degradation rates of proteins. O-linked N-acetylglucosamine
      transferase (OGT), an enzyme used for addition of O-GlcNAc during O
      GlcNAcylation, is identified as a key regulator to promote oncogenesis in a
      feedback mechanism through the stabilization of c-Myc. Silencing of the OGT and c
      Myc loop decreases glycolytic flux and leads to programmed cell death. Results of
      network analyses also identify a significant cycle that highlights the role of
      p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. Together, our
      findings suggest that the OGT and c-Myc feedback loop is critical in tumor
      progression, and targeting these mediators may provide a mechanism-based
      therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer.

PMID- 27703844
TI  - Investigating the spatial distribution and effects of nearshore topography on
      Acropora cervicornis abundance in Southeast Florida.
AB  - Dense Acropora cervicornis aggregations, or patches, have been documented within
      nearshore habitats in Southeast Florida (SE FL) despite close proximity to
      numerous anthropogenic stressors and subjection to frequent natural disturbance
      events. Limited information has been published concerning the distribution and
      abundance of A. cervicornis outside of these known dense patches. The first goal
      of this study was to conduct a spatially extensive and inclusive survey (9.78
      km2) to determine whether A. cervicornis distribution in the nearshore habitat of
      SE FL was spatially uniform or clustered. The second goal was to investigate
      potential relationships between broad-scale seafloor topography and A.
      cervicornis abundance using high resolution bathymetric data. Acropora
      cervicornis was distributed throughout the study area, and the Getis-Ord Gi*
      statistic and Anselin Local Moran's I spatial cluster analysis showed significant
      clustering along topographic features termed ridge crests. Significant clustering
      was further supported by the inverse distance weighted surface model. Ordinal
      logistic regression indicated 1) as distance from a ridge increases, odds of
      reduced A. cervicornis abundance increases; 2) as topographic elevation
      increases, odds of increased abundance increases; and 3) as mean depth increases,
      odds of increased abundance increases. This study provides detailed information
      on A. cervicornis distribution and abundance at a regional scale and supports
      modeling its distributions in similar habitats elsewhere throughout the western
      Atlantic and Caribbean. Acropora cervicornis is frequently observed and in areas
      an abundant species within the nearshore habitat along the SE FL portion of the
      Florida Reef Tract (FRT). This study provides a better understanding of local
      habitat associations thus facilitating appropriate management of the nearshore
      environment and species conservation. The portion of the FRT between Hillsboro
      and Port Everglades inlets should be considered for increased management and
      protection to reduce local stressors.

PMID- 27703843
TI  - XA21-specific induction of stress-related genes following Xanthomonas infection
      of detached rice leaves.
AB  - The rice XA21 receptor kinase confers robust resistance to the bacterial pathogen
      Xanthomonas oryzaepv. oryzae (Xoo). We developed a detached leaf infection assay
      to quickly and reliably measure activation of the XA21-mediated immune response
      using genetic markers. We used RNA sequencing of elf18 treated EFR:XA21:GFP
      plants to identify candidate genes that could serve as markers for XA21
      activation. From this analysis, we identified eight genes that are up-regulated
      in both in elf18 treated EFR:XA21:GFP rice leaves and Xoo infected XA21 rice
      leaves. These results provide a rapid and reliable method to assess bacterial
      rice interactions.

PMID- 27703846
TI  - Dynamics and stability of directional jumps in the desert locust.
AB  - Locusts are known for their ability to jump large distances to avoid predation.
      The jump also serves to launch the adult locust into the air in order to initiate
      flight. Various aspects of this important behavior have been studied extensively,
      from muscle physiology and biomechanics, to the energy storage systems involved
      in powering the jump, and more. Less well understood are the mechanisms
      participating in control of the jump trajectory. Here we utilise video monitoring
      and careful analysis of experimental directional jumps by adult desert locusts,
      together with dynamic computer simulation, in order to understand how the locusts
      control the direction and elevation of the jump, the residual angular velocities
      resulting from the jump and the timing of flapping-flight initiation. Our study
      confirms and expands early findings regarding the instrumental role of the
      initial body position and orientation. Both real-jump video analysis and
      simulations based on our expanded dynamical model demonstrate that the initial
      body coordinates of position (relative to the hind-legs ground-contact points)
      are dominant in predicting the jumps' azimuth and elevation angles. We also
      report a strong linear correlation between the jumps' pitch-angular-velocity and
      flight initiation timing, such that head downwards rotations lead to earlier wing
      opening. In addition to offering important insights into the bio-mechanical
      principles of locust jumping and flight initiation, the findings from this study
      will be used in designing future prototypes of a bio-inspired miniature jumping
      robot that will be employed in animal behaviour studies and environmental
      monitoring applications.

PMID- 27703847
TI  - Genetic diversity of Poa pratensis L. depending on geographical origin and
      compared with genetic markers.
AB  - BACKGROUND: Poa pratensis is one of the most common species of meadow grass in
      Europe. Most cultivars of the species found in Poland were originally derived
      from its ecotypes. We compared the effectiveness of the RAPD and ISSR methods in
      assessing the genetic diversity of the selected populations of P. pratensis. We
      examined whether these methods could be useful for detecting a possible link
      between the geographical origin of a given population and its assessed genetic
      variation. METHODS: The molecular markers RAPD and ISSR were used and their
      efficiency compared using, inter alia, statistical multivariate methods (UPGMA
      and PCA). RESULTS: The low value of Dice's coefficient (0.369) along with the
      significantly high percentage of polymorphic products indicates a substantial
      degree of genetic diversity among the studied populations. Our results found a
      correlation between the geographical origin of the studied populations and their
      genetic variations. For ISSR, which proved to be the more effective method in
      that respect, we selected primers with the greatest differentiating powers
      correlating to geographical origin. DISCUSSION: The populations evaluated in this
      study were characterized by a high genetic diversity. This seems to confirm the
      hypothesis that ecotypes of P. pratensis originating from different regions of
      Central Europe with different terrain structures and habitat conditions can be a
      source of great genetic variability.

PMID- 27703848
TI  - Reproductive ecology and isolation of Psittacanthus calyculatus and P.
      auriculatus mistletoes (Loranthaceae).
AB  - BACKGROUND: Relationships between floral biology and pollinator behavior are
      important to understanding species diversity of hemiparasitic Psittacanthus
      mistletoes (c. 120 species). We aimed to investigate trait divergence linked to
      pollinator attraction and reproductive isolation (RI) in two hummingbird
      pollinated and bird-dispersed Psittacanthus species with range overlap. METHODS:
      We investigated the phylogenetic relationships, floral biology, pollinator
      assemblages, seed dispersers and host usage, and the breeding system and female
      reproductive success of two sympatric populations of P. calyculatus and P.
      auriculatus, and one allopatric population of P. calyculatus. Flowers in sympatry
      were also reciprocally pollinated to assess a post-mating component of RI.
      RESULTS: Hummingbird assemblages differed between calyculatus populations, while
      allopatric plants of calyculatus opened more but smaller flowers with longer
      lifespans and produced less nectar than those in sympatry. Bayesian-based
      phylogenetic analysis indicated monophyly for calyculatus populations (i.e. both
      populations belong to the same species). In sympatry, calyculatus plants opened
      more and larger flowers with longer lifespans and produced same nectar volume
      than those of auriculatus; populations shared pollinators but seed dispersers and
      host usage differed between species. Nectar standing crops differed between
      sympatric populations, with lower visitation in calyculatus. Hand pollination
      experiments indicated a predominant outcrossing breeding system, with fruit set
      after interspecific pollination two times higher from calyculatus to auriculatus
      than in the opposite direction. CONCLUSIONS: Given the low genetic
      differentiation between calyculatus populations, observed trait divergence could
      have resulted from changes regarding the local communities of pollinators and,
      therefore, expected divergence for peripheral, allopatric populations. Using RI
      estimates, there were fewer heterospecific matings than expected by chance in P.
      calyculatus (RI4A = 0.629) as compared to P. auriculatus (RI4A = 0.20). When
      considering other factors of ecological isolation that affect co-occurrence, the
      RI4C values indicate that isolation by hummingbird pollinators was less effective
      (0.20) than isolation by host tree species and seed dispersers (0.80 and 0.60,
      respectively), suggesting that host usage is the most important ecological
      isolation factor between the two species. Accordingly, the absolute and relative
      cumulative strength values indicated that the host tree species' barrier is
      currently contributing the most to maintaining these species in sympatry.

PMID- 27703845
TI  - Identify potential drugs for cardiovascular diseases caused by stress-induced
      genes in vascular smooth muscle cells.
AB  - BACKGROUND: Abnormal proliferation of vascular smooth muscle cells (VSMC) is a
      major cause of cardiovascular diseases (CVDs). Many studies suggest that vascular
      injury triggers VSMC dedifferentiation, which results in VSMC changes from a
      contractile to a synthetic phenotype; however, the underlying molecular
      mechanisms are still unclear. METHODS: In this study, we examined how VSMC
      responds under mechanical stress by using time-course microarray data. A three
      phase study was proposed to investigate the stress-induced differentially
      expressed genes (DEGs) in VSMC. First, DEGs were identified by using the
      moderated t-statistics test. Second, more DEGs were inferred by using the
      Gaussian Graphical Model (GGM). Finally, the topological parameters-based method
      and cluster analysis approach were employed to predict the last batch of DEGs. To
      identify the potential drugs for vascular diseases involve VSMC proliferation,
      the drug-gene interaction database, Connectivity Map (cMap) was employed. Success
      of the predictions were determined using in-vitro data, i.e. MTT and clonogenic
      assay. RESULTS: Based on the differential expression calculation, at least 23
      DEGs were found, and the findings were qualified by previous studies on VSMC. The
      results of gene set enrichment analysis indicated that the most often found
      enriched biological processes are cell-cycle-related processes. Furthermore, more
      stress-induced genes, well supported by literature, were found by applying graph
      theory to the gene association network (GAN). Finally, we showed that by
      processing the cMap input queries with a cluster algorithm, we achieved a
      substantial increase in the number of potential drugs with experimental IC50
      measurements. With this novel approach, we have not only successfully identified
      the DEGs, but also improved the DEGs prediction by performing the topological and
      cluster analysis. Moreover, the findings are remarkably validated and in line
      with the literature. Furthermore, the cMap and DrugBank resources were used to
      identify potential drugs and targeted genes for vascular diseases involve VSMC
      proliferation. Our findings are supported by in-vitro experimental IC50, binding
      activity data and clinical trials. CONCLUSION: This study provides a systematic
      strategy to discover potential drugs and target genes, by which we hope to shed
      light on the treatments of VSMC proliferation associated diseases.

PMID- 27703849
TI  - Atlantic salmon (Salmo salar) require increased dietary levels of B-vitamins when
      fed diets with high inclusion of plant based ingredients.
AB  - Aiming to re-evaluate current recommendations for nutrient supplementations when
      Atlantic salmon are fed diets based on plant ingredients, two regression
      experiments, with parr and post-smolt, were conducted. A control diet was
      included to evaluate if ingredients supplied sufficient nutrients without any
      added nutrient package (NP). The nutrient package consisted of vitamins B, C, E,
      minerals, cholesterol, methionine, taurine and histidine. This paper focus on B
      vitamins. In parr, growth, health and welfare parameters responded on NP
      additions, but this was not observed in the seawater stage. During three months
      of feeding, parr tripled their weight. Parr given diets added the NP above NRC
      (2011) showed improved protein retention, and reduced liver and viscera indices.
      Post-smolt fed the same diets during five months showed a doubling of weight, but
      did not respond to the variation in NP to the same extent as parr. Significant
      regressions were obtained in body compartments for several of the B-vitamins in
      the premix. Whole body biotin concentration was unaffected by micronutrient
      premix level, and mRNA expression of the enzymes dependent of biotin showed only
      weak increases with increased biotin. Muscle thiamine plateaued at a diet level
      similar to NRC (2011) recommendation in freshwater, and showed stable values
      independent on premix addition in seawater. The mRNA expression of the enzyme
      G6PDH (glucose-6-phosphate dehydrogenase) is sensitive to thiamine availability;
      results did not indicate any need to add thiamine above levels recommended for
      fish in general. Niacin showed a steady increase in whole body concentrations as
      feed niacin increased. Muscle riboflavin peaked at a diet level of 12.4 mg kg-1.
      Sufficient riboflavin is important to avoid e.g., development of cataract.
      Cataract was not registered to be any problem, neither in fresh- nor in seawater.
      Cobalamin (B 12) in muscle and liver was saturated at 0.17 mg kg-1 diet. Muscle
      pyridoxine showed a dose-dependent level in muscle, and peaked around 10 mg kg -1
      diet. White muscle ASAT (asparagine amino transferase) activity steadily
      increased, with indications of stable values when dietary pyridoxine was around
      10-16 mg kg -1 diet. Pantothenic acid increased in gill tissue up to a level of
      5.5 mg kg -1 soft gill tissue; at a dietary level of 22 mg kg-1. Improved
      performance, and coverage of metabolic need for niacin was at a dietary level of
      66 mg kg -1, riboflavin 10-12 mg kg-1, pyridoxine 10 mg kg-1 and panthotenic acid
      22 mg kg-1. Based on these results, recommended B-vitamin supplementation in
      plant based diets for Atlantic salmon should be adjusted.

PMID- 27703850
TI  - Enzymatically crosslinked gelatin hydrogel promotes the proliferation of adipose
      tissue-derived stromal cells.
AB  - Gelatin hydrogel crosslinked by microbial transglutaminase (mTG) exhibits
      excellent performance in cell adhesion, proliferation, and differentiation. We
      examined the gelation time and gel strength of gelatin/mTG hydrogels in various
      proportions to investigate their physical properties and tested their degradation
      performances in vitro. Cell morphology and viability of adipose tissue-derived
      stromal cells (ADSCs) cultured on the 2D gel surface or in 3D hydrogel
      encapsulation were evaluated by immunofluorescence staining. Cell proliferation
      was tested via Alamar Blue assay. To investigate the hydrogel effect on cell
      differentiation, the cardiac-specific gene expression levelsof Nkx2.5, Myh6,
      Gja1, and Mef2c in encapsulated ADSCs with or without cardiac induction medium
      were detected by real-time RT-PCR. Cell release from the encapsulated status and
      cell migration in a 3D hydrogel model were assessed in vitro. Results show that
      the gelatin/mTG hydrogels are not cytotoxic and that their mechanical properties
      are adjustable. Hydrogel degradation is related to gel concentration and the
      resident cells. Cell growth morphology and proliferative capability in both 2D
      and 3D cultures were mainly affected by gel concentration. PCR result shows that
      hydrogel modulus together with induction medium affects the cardiac
      differentiation of ADSCs. The cell migration experiment and subcutaneous
      implantation show that the hydrogels are suitable for cell delivery.

PMID- 27703852
TI  - An early bothremydid (Testudines, Pleurodira) from the Late Cretaceous
      (Cenomanian) of Utah, North America.
AB  - BACKGROUND: Bothremydidae is a clade of extinct pleurodiran turtles known from
      the Cretaceous to Paleogene of Africa, Europe, India, Madagascar, and North and
      South America. The group is most diverse during the Late Cretaceous to Paleogene
      of Africa. Little is known, however, about the early evolution of the group.
      METHODS: We here figure and describe a fossil turtle from early Late Cretaceous
      deposits exposed at MacFarlane Mine in Cedar Canyon, southwestern Utah, USA. The
      sediments associated with the new turtle are utilized to infer its stratigraphic
      provenience and the depositional settings in which it was deposited. The fossil
      is compared to previously described fossil pleurodires, integrated into a
      modified phylogenetic analysis of pelomedusoid turtles, and the biogeography of
      bothremydid turtles is reassessed. In light of the novel phylogenetic hypotheses,
      six previously established taxon names are converted to phylogenetically defined
      clade names to aid communication. RESULTS: The new fossil turtle can be inferred
      with confidence to have originated from a brackish water facies within the late
      Cenomanian Culver Coal Zone of the Naturita Formation. The fossil can be
      distinguished from all other previously described pleurodires and is therefore
      designated as a new taxon, Paiutemys tibert gen. et. sp. nov. Phylogenetic
      analysis places the new taxon as sister to the European Polysternon provinciale,
      Foxemys trabanti and Foxemys mechinorum at the base of Bothremydinae.
      Biogeographic analysis suggests that bothremydids originated as continental
      turtles in Gondwana, but that bothremydines adapted to near-shore marine
      conditions and therefore should be seen as having a circum-Atlantic distribution.

PMID- 27703851
TI  - Evolution history of duplicated smad3 genes in teleost: insights from Japanese
      flounder, Paralichthys olivaceus.
AB  - Following the two rounds of whole-genome duplication (WGD) during deuterosome
      evolution, a third genome duplication occurred in the ray-fined fish lineage and
      is considered to be responsible for the teleost-specific lineage diversification
      and regulation mechanisms. As a receptor-regulated SMAD (R-SMAD), the function of
      SMAD3 was widely studied in mammals. However, limited information of its role or
      putative paralogs is available in ray-finned fishes. In this study, two SMAD3
      paralogs were first identified in the transcriptome and genome of Japanese
      flounder (Paralichthys olivaceus). We also explored SMAD3 duplication in other
      selected species. Following identification, genomic structure, phylogenetic
      reconstruction, and synteny analyses performed by MrBayes and online
      bioinformatic tools confirmed that smad3a/3b most likely originated from the
      teleost-specific WGD. Additionally, selection pressure analysis and expression
      pattern of the two genes performed by PAML and quantitative real-time PCR (qRT
      PCR) revealed evidence of subfunctionalization of the two SMAD3 paralogs in
      teleost. Our results indicate that two SMAD3 genes originate from teleost
      specific WGD, remain transcriptionally active, and may have likely undergone
      subfunctionalization. This study provides novel insights to the evolution fates
      of smad3a/3b and draws attentions to future function analysis of SMAD3 gene
      family.

PMID- 27703855
TI  - Accuracy of conventional identification methods used for Enterobacteriaceae
      isolates in three Nigerian hospitals.
AB  - BACKGROUND: Enterobacteriaceae are ubiquitously present in nature and can be
      found in the intestinal tract of humans and animals as commensal flora. Multidrug
      resistant Enterobacteriaceae are increasingly reported and are a threat to public
      health implicating a need for accurate identification of the isolates to species
      level. In developing countries, identification of bacteria basically depends on
      conventional methods: culture and phenotypic methods that hamper the accurate
      identification of bacteria. In this study, matrix-assisted desorption ionization
      time of flight mass spectrometry (MALDI-TOF MS) technique was compared to
      conventional identification techniques. MATERIALS AND METHODS: In total, 147
      Enterobacteriaceae isolates were collected from March to May 2015 from three
      medical microbiology laboratories of hospitals in Edo state, Nigeria, after being
      tested according to the individual laboratories standard operating procedures.
      All isolates were stored at -20 degrees C until tested centrally by MALDI-TOF MS.
      RESULTS: One hundred and forty five (98.6%) isolates had a MALDI Biotyper best
      score > or =2.0, indicating a secure genus and probable species identification;
      and 2(1.36%) isolates had a best score <2.0 indicating probable genus
      identification. Isolates with best scores of > or =2.0 comprised nine genera and
      10 species, respectively. A total of 57.2% and 33.1% of isolates identified had
      agreement between MALDI-TOF MS and conventional techniques for identification at
      genus and species level, respectively, when analyzing bacteria with MALDI
      Biotyper best scores > or =2.0. CONCLUSION: The results of our study show that
      the applied conventional identification techniques for Enterobacteriaceae in the
      investigated Nigerian hospitals are not very accurate. Use of state-of-the-art
      identification technologies for microorganisms is necessary to guarantee
      comparability of bacteriological results.

PMID- 27703853
TI  - A direct CO2 control system for ocean acidification experiments: testing effects
      on the coralline red algae Phymatolithon lusitanicum.
AB  - Most ocean acidification (OA) experimental systems rely on pH as an indirect way
      to control CO2. However, accurate pH measurements are difficult to obtain and
      shifts in temperature and/or salinity alter the relationship between pH and pCO2.
      Here we describe a system in which the target pCO2 is controlled via direct
      analysis of pCO2 in seawater. This direct type of control accommodates potential
      temperature and salinity shifts, as the target variable is directly measured
      instead of being estimated. Water in a header tank is permanently re-circulated
      through an air-water equilibrator. The equilibrated air is then routed to an
      infrared gas analyzer (IRGA) that measures pCO2 and conveys this value to a
      Proportional-Integral-Derivative (PID) controller. The controller commands a
      solenoid valve that opens and closes the CO2 flush that is bubbled into the
      header tank. This low-cost control system allows the maintenance of stabilized
      levels of pCO2 for extended periods of time ensuring accurate experimental
      conditions. This system was used to study the long term effect of OA on the
      coralline red algae Phymatolithon lusitanicum. We found that after 11 months of
      high CO2 exposure, photosynthesis increased with CO2 as opposed to respiration,
      which was positively affected by temperature. Results showed that this system is
      adequate to run long-term OA experiments and can be easily adapted to test other
      relevant variables simultaneously with CO2, such as temperature, irradiance and
      nutrients.

PMID- 27703854
TI  - Sex differences in pacing during 'Ultraman Hawaii'.
AB  - BACKGROUND: To date, little is known for pacing in ultra-endurance athletes
      competing in a non-stop event and in a multi-stage event, and especially, about
      pacing in a multi-stage event with different disciplines during the stages.
      Therefore, the aim of the present study was to examine the effect of age, sex and
      calendar year on triathlon performance and variation of performance by events
      (i.e., swimming, cycling 1, cycling 2 and running) in 'Ultraman Hawaii' held
      between 1983 and 2015. METHODS: Within each sex, participants were grouped in
      quartiles (i.e., Q1, Q2, Q3 and Q4) with Q1 being the fastest (i.e., lowest
      overall time) and Q4 the slowest (i.e., highest overall time). To compare
      performance among events (i.e., swimming, cycling 1, cycling 2 and running), race
      time in each event was converted in z score and this value was used for further
      analysis. RESULTS: A between-within subjects ANOVA showed a large sex * event (p
      = 0.015, eta2 = 0.014) and a medium performance group * event interaction (p =
      0.001, eta2 = 0.012). No main effect of event on performance was observed (p =
      0.174, eta2 = 0.007). With regard to the sex * event interaction, three female
      performance groups (i.e., Q2, Q3 and Q4) increased race time from swimming to
      cycling 1, whereas only one male performance group (Q4) revealed a similar trend.
      From cycling 1 to cycling 2, the two slower female groups (Q3 and Q4) and the
      slowest male group (Q4) increased raced time. In women, the fastest group
      decreased (i.e., improved) race time from swimming to cycling 1 and thereafter,
      maintained performance, whereas in men, the fastest group decreased race time
      till cycling 2 and increased it in the running. CONCLUSION: In summary, women
      pace differently than men during 'Ultraman Hawaii' where the fastest women
      decreased performance on day 1 and could then maintain on day 2 and 3, whereas
      the fastest men worsened performance on day 1 and 2 but improved on day 3.

PMID- 27703856
TI  - Actin-dependence of the chloroplast cold positioning response in the liverwort
      Marchantia polymorpha L.
AB  - The subcellular positioning of chloroplasts can be changed by alterations in the
      environment such as light and temperature. For example, in leaf mesophyll cells,
      chloroplasts localize along anticlinal cell walls under high-intensity light, and
      along periclinal cell walls under low-intensity light. These types of positioning
      responses are involved in photosynthetic optimization. In light-mediated
      chloroplast positioning responses, chloroplasts move to the appropriate positions
      in an actin-dependent manner, although some exceptions also depend on
      microtubule. Even under low-intensity light, at low temperature (e.g., 5 degrees
      C), chloroplasts localize along anticlinal cell walls; this phenomenon is termed
      chloroplast cold positioning. In this study, we analyzed whether chloroplast cold
      positioning is dependent on actin filaments and/or microtubules in the liverwort
      Marchantia polymorpha L. When liverwort cells were treated with drugs for the de
      polymerization of actin filaments, chloroplast cold positioning was completely
      inhibited. In contrast, chloroplast cold positioning was not affected by
      treatment with a drug for the de-polymerization of microtubules. These
      observations indicate the actin-dependence of chloroplast cold positioning in M.
      polymorpha. Actin filaments during the chloroplast cold positioning response were
      visualized by using fluorescent probes based on fluorescent proteins in living
      liverwort cells, and thus, their behavior during the chloroplast cold positioning
      response was documented.

PMID- 27703858
TI  - Not always a matter of context: direct effects of red on arousal but context
      dependent moderations on valence.
AB  - The arousal theory of color proposes that red is associated with arousal.
      Research on the color-in-context theory, in turn, states that the context in
      which red is perceived influences its valence-related meaning and behavioral
      responses to it. This study faces and integrates these theories by examining the
      influence of red on both arousal and valence perceptions of test-relevant and
      neutral stimuli, rendering a color 2 (red vs. blue) * context 2 (test vs.
      neutral) between-subjects design. Participants rated different pictures regarding
      their arousal and valence component, respectively. In line with the assumptions
      of both theories, red increased arousal perceptions of stimuli irrespective of
      their valence but a context * color interaction was found for valence
      perceptions: for participants viewing test-relevant pictures, red increased their
      perceptions of negativity compared to neutral pictures. The present study shows
      that both theories are actually compatible when differentiating the arousal and
      valence component.

PMID- 27703857
TI  - The origin of widespread species in a poor dispersing lineage (diving beetle
      genus Deronectes).
AB  - In most lineages, most species have restricted geographic ranges, with only few
      reaching widespread distributions. How these widespread species reached their
      current ranges is an intriguing biogeographic and evolutionary question,
      especially in groups known to be poor dispersers. We reconstructed the
      biogeographic and temporal origin of the widespread species in a lineage with
      particularly poor dispersal capabilities, the diving beetle genus Deronectes
      (Dytiscidae). Most of the ca. 60 described species of Deronectes have narrow
      ranges in the Mediterranean area, with only four species with widespread European
      distributions. We sequenced four mitochondrial and two nuclear genes of 297
      specimens of 109 different populations covering the entire distribution of the
      four lineages of Deronectes, including widespread species. Using Bayesian
      probabilities with an a priori evolutionary rate, we performed (1) a global
      phylogeny/phylogeography to estimate the relationships of the main lineages
      within each group and root them, and (2) demographic analyses of the best
      population coalescent model for each species group, including a reconstruction of
      the geographical history estimated from the distribution of the sampled
      localities. We also selected 56 specimens to test for the presence of Wolbachia,
      a maternally transmitted parasite that can alter the patterns of mtDNA
      variability. All species of the four studied groups originated in the southern
      Mediterranean peninsulas and were estimated to be of Pleistocene origin. In three
      of the four widespread species, the central and northern European populations
      were nested within those in the northern areas of the Anatolian, Balkan and
      Iberian peninsulas respectively, suggesting a range expansion at the edge of the
      southern refugia. In the Mediterranean peninsulas the widespread European species
      were replaced by vicariant taxa of recent origin. The fourth species (D. moestus)
      was proven to be a composite of unrecognised lineages with more restricted
      distributions around the Western and Central Mediterranean. The analysis of
      Wolbachia showed a high prevalence of infection among Deronectes, especially in
      the D. aubei group, where all sequenced populations were infected with the only
      exception of the Cantabrian Mountains, the westernmost area of distribution of
      the lineage. In this group there was a phylogenetic incongruence between the
      mitochondrial and the nuclear sequence, although no clear pattern links this
      discordance to the Wolbachia infection. Our results suggest that, in different
      glacial cycles, populations that happened to be at the edge of the newly
      deglaciated areas took advantage of the optimal ecological conditions to expand
      their ranges to central and northern Europe. Once this favourable ecological
      window ended populations become isolated, resulting in the presence of closely
      related but distinct species in the Mediterranean peninsulas.

PMID- 27703859
TI  - Targeted genomic enrichment and sequencing of CyHV-3 from carp tissues confirms
      low nucleotide diversity and mixed genotype infections.
AB  - Koi herpesvirus disease (KHVD) is an emerging disease that causes mass mortality
      in koi and common carp, Cyprinus carpio L. Its causative agent is Cyprinid
      herpesvirus 3 (CyHV-3), also known as koi herpesvirus (KHV). Although data on the
      pathogenesis of this deadly virus is relatively abundant in the literature, still
      little is known about its genomic diversity and about the molecular mechanisms
      that lead to such a high virulence. In this context, we developed a new strategy
      for sequencing full-length CyHV-3 genomes directly from infected fish tissues.
      Total genomic DNA extracted from carp gill tissue was specifically enriched with
      CyHV-3 sequences through hybridization to a set of nearly 2 million overlapping
      probes designed to cover the entire genome length, using KHV-J sequence (GenBank
      accession number AP008984) as reference. Applied to 7 CyHV-3 specimens from
      Poland and Indonesia, this targeted genomic enrichment enabled recovery of the
      full genomes with >99.9% reference coverage. The enrichment rate was directly
      correlated to the estimated number of viral copies contained in the DNA extracts
      used for library preparation, which varied between ~5000 and ~2*107. The average
      sequencing depth was >200 for all samples, thus allowing the search for variants
      with high confidence. Sequence analyses highlighted a significant proportion of
      intra-specimen sequence heterogeneity, suggesting the presence of mixed
      infections in all investigated fish. They also showed that inter-specimen genetic
      diversity at the genome scale was very low (>99.95% of sequence identity). By
      enabling full genome comparisons directly from infected fish tissues, this new
      method will be valuable to trace outbreaks rapidly and at a reasonable cost, and
      in turn to understand the transmission routes of CyHV-3.

PMID- 27703860
TI  - Influence of age and sex on winter site fidelity of sanderlings Calidris alba.
AB  - Many migratory bird species show high levels of site fidelity to their wintering
      sites, which confers advantages due to prior knowledge, but may also limit the
      ability of the individual to move away from degrading sites or to detect
      alternative foraging opportunities. Winter site fidelity often varies among age
      groups, but sexual differences have seldom been recorded in birds. We studied a
      population of individually colour-marked sanderlings wintering in and around the
      Tejo estuary, a large estuarine wetland on the western coast of Portugal. For 160
      individuals, sighted a total of 1,249 times between November 2009 and March 2013,
      we calculated the probability that they moved among five distinct wintering sites
      and how this probability is affected by distance between them. To compare site
      fidelity among age classes and sexes, as well as within the same winter and over
      multiple winters, we used a Site Fidelity Index (SFI). Birds were sexed using a
      discriminant function based on biometrics of a large set of molecularly sexed
      sanderlings (n = 990). The vast majority of birds were observed at one site only,
      and the probability of the few detected movements between sites was negatively
      correlated with the distance among each pair of sites. Hardly any movements were
      recorded over more than 15 km, suggesting small home ranges. SFI values indicated
      that juveniles were less site-faithful than adults which may reflect the
      accumulated knowledge and/or dominance of older animals. Among adults, females
      were significantly less site faithful than males. A sexual difference in winter
      site fidelity is unusual in shorebirds. SFI values show site-faithfulness is
      lower when multiple winters were considered, and most birds seem to chose a
      wintering site early in the season and use that site throughout the winter.
      Sanderlings show a very limited tendency to explore alternative wintering
      options, which might have implications for their survival when facing habitat
      change or loss (e.g., like severe beach erosion as can be the case at one of the
      study sites).

PMID- 27703861
TI  - Feeding bovine milks with low or high IgA levels is associated with altered re
      establishment of murine intestinal microbiota after antibiotic treatment.
AB  - Antibiotics are a vital and commonly used therapeutic tool, but their use also
      results in profound changes in the intestinal microbiota that can, in turn, have
      significant health consequences. Understanding how the microbiota recovers after
      antibiotic treatment will help to devise strategies for mitigating the adverse
      effects of antibiotics. Using a mouse model, we have characterized the changes
      occurring in the intestinal microbiota immediately after five days exposure to
      ampicillin, and then at three and fourteen days thereafter. During the fourteen
      day period of antibiotic recovery, groups of mice were fed either water, cows'
      milk containing high levels of IgA, or cows' milk containing low levels of IgA as
      their sole source of liquid. Effects on microbiota of feeding milks for 14 days
      were also assessed in groups of mice that had no ampicillin exposure. Changes in
      microbiota were measured by high throughput sequencing of the V4 to V6 variable
      regions of the 16S ribosomal RNA gene. As expected, exposure to ampicillin led to
      profound changes to the types and abundance of bacteria present, along with a
      loss of diversity. At 14 days following antibiotic exposure, mice fed water had
      recovered microbiota compositions similar to that prior to antibiotics. However,
      feeding High-IgA milk to mice that has been exposed to antibiotics was associated
      with altered microbiota compositions, including increased relative abundance of
      Lactobacillus and Barnesiella compared to the start of the study. Mice exposed to
      antibiotics then fed Low-IgA milk also showed increased Barnesiella at day 14.
      Mice without antibiotic perturbation, showed no change in their microbiota after
      14 days of milk feeding. Overall, these findings add to a knowledge platform for
      optimizing intestinal function after treatment with antibiotics in the human
      population.

PMID- 27703862
TI  - Reef-scale trends in Florida Acropora spp. abundance and the effects of
      population enhancement.
AB  - Since the listing of Acropora palmata and A. cervicornis under the US Endangered
      Species Act in 2006, increasing investments have been made in propagation of
      listed corals (primarily A. cervicornis, A. palmata to a much lesser extent) in
      offshore coral nurseries and outplanting cultured fragments to reef habitats.
      This investment is superimposed over a spatiotemporal patchwork of ongoing
      disturbances (especially storms, thermal bleaching, and disease) as well as the
      potential for natural population recovery. In 2014 and 2015, we repeated broad
      scale (>50 ha), low precision Acropora spp. censuses (i.e., direct observation by
      snorkelers documented via handheld GPS) originally conducted in appropriate reef
      habitats during 2005-2007 to evaluate the trajectory of local populations and the
      effect of population enhancement. Over the decade-long study, A. palmata showed a
      cumulative proportional decline of 0.4 -0.7x in colony density across all sites,
      despite very low levels of outplanting at some sites. A. cervicornis showed
      similar proportional declines at sites without outplanting. In contrast, sites
      that received A. cervicornis outplants showed a dramatic increase in density
      (over 13x). Indeed, change in A. cervicornis colony density was significantly
      positively correlated with cumulative numbers of outplants across sites. This
      study documents a substantive reef-scale benefit of Acropora spp. population
      enhancement in the Florida Keys, when performed at adequate levels, against a
      backdrop of ongoing population decline.

PMID- 27703863
TI  - Noise pollution has limited effects on nocturnal vigilance in peahens.
AB  - Natural environments are increasingly exposed to high levels of noise pollution.
      Noise pollution can alter the behavior of animals but we know little about its
      effects on antipredator behavior. We therefore investigated the impact of noise
      pollution on vigilance behavior and roost selection in an avian species, peafowl
      (Pavo cristatus), that inhabits urban environments. Captive peahens were exposed
      to noise pollution at night and their vigilance levels and roost selections were
      monitored. The vigilance levels of peahens were unaffected by exposure to noise
      pollution within trials. Furthermore, the peahens exhibited no preference for
      roosting farther or closer to noise pollution. Interestingly, predators often
      avoided the experimental area during nights with noise pollution, which could
      explain why vigilance rates were higher overall during control compared to noise
      trials. The results suggest that peahens' perception of risk is not drastically
      impacted by noise pollution but longer-term studies will be necessary to assess
      any chronic effects.

PMID- 27703864
TI  - Discovery pattern and species number of scale insects (Hemiptera: Coccoidea).
AB  - Few investigations have been made of the species description trend of scale
      insects. The present study reports the discovery pattern and taxonomic efforts
      for this group based on global species and a literature dataset. In addition,
      three asymptotic models (Logistic, Gompertz, and Extreme Value) based on a
      discovery curve were used to predict the species number of scale insects. Our
      results showed that the species description rate has been changing over time,
      with certain peaks and valleys in the past 250 years. The mean number of species
      described per year was 30, with the highest number of 195 described species in
      1985. The increasing number of authors and the almost constant proportion of
      species described by 10% most prolific authors since the 1900s suggested that
      taxonomic effort has been increasing over time. The Gompertz model with lowest
      AIC value suggested that there are about 10,450 species of scale insects on
      Earth, nearly 30% of which remain to be described. Our study offers insights into
      the discovery pattern of scale insect diversity.

PMID- 27703865
TI  - Bacterial community diversity of the deep-sea octocoral Paramuricea placomus.
AB  - Compared to tropical corals, much less is known about deep-sea coral biology and
      ecology. Although the microbial communities of some deep-sea corals have been
      described, this is the first study to characterize the bacterial community
      associated with the deep-sea octocoral, Paramuricea placomus. Samples from five
      colonies of P. placomus were collected from Baltimore Canyon (379-382 m depth) in
      the Atlantic Ocean off the east coast of the United States of America. DNA was
      extracted from the coral samples and 16S rRNA gene amplicons were pyrosequenced
      using V4-V5 primers. Three samples sequenced deeply (>4,000 sequences each) and
      were further analyzed. The dominant microbial phylum was Proteobacteria, but
      other major phyla included Firmicutes and Planctomycetes. A conserved community
      of bacterial taxa held in common across the three P. placomus colonies was
      identified, comprising 68-90% of the total bacterial community depending on the
      coral individual. The bacterial community of P. placomus does not appear to
      include the genus Endozoicomonas, which has been found previously to be the
      dominant bacterial associate in several temperate and tropical gorgonians.
      Inferred functionality suggests the possibility of nitrogen cycling by the core
      bacterial community.

PMID- 27703867
TI  - Hierarchical multistate models from population data: an application to parity
      statuses.
AB  - Hierarchical models are characterized by having N living states connected by N -
      1 rates of transfer. Demographic measures for such models can be calculated
      directly from counts of the number of persons in each state at two nearby points
      in time. Exploiting the ability of population stocks to determine the flows in
      hierarchical models expands the range of demographic analysis. The value of such
      analyses is illustrated by an application to childbearing, where the states of
      interest reflect the number of children a woman has born. Using Census data on
      the distribution of women by age and parity, a parity status life table for US
      Women, 2005-2010, is constructed. That analysis shows that nearly a quarter of
      American women are likely to remain childless, with a 0-3 child pattern replacing
      the 2-4 child pattern of the past.

PMID- 27703868
TI  - Deer herbivory reduces web-building spider abundance by simplifying forest
      vegetation structure.
AB  - Indirect ecological effects are a common feature of ecological systems, arising
      when one species affects interactions among two or more other species. We
      examined how browsing by white-tailed deer (Odocoileus virginianus) indirectly
      affected the abundance and composition of a web-building spider guild through
      their effects on the structure of the ground and shrub layers of northern
      hardwood forests. We examined paired plots consisting of deer-free and control
      plots in the Allegheny Plateau region Pennsylvania and Northern Highlands region
      of Wisconsin. We recorded the abundance of seven types of webs, each
      corresponding to a family of web-building spiders. We quantified vegetation
      structure and habitat suitability for the spiders by computing a web scaffold
      availability index (WSAI) at 0.5 m and 1.0 m above the ground. At Northern
      Highlands sites, we recorded prey availability. Spider webs were twice as
      abundant in deer-free plots compared to control plots, while WSAI was 7-12 times
      greater in deerfree plots. Prey availability was lower in deer-free plots. With
      the exception of funnel web-builders, all spider web types were significantly
      more abundant in deer-free plots. Both deer exclusion and the geographic region
      of plots were significant predictors of spider community structure. In closed
      canopy forests with high browsing pressure, the low density of tree saplings and
      shrubs provides few locations for web-building spiders to anchor webs.
      Recruitment of these spiders may become coupled with forest disturbance events
      that increase tree and shrub recruitment. By modifying habitat structure, deer
      appear to indirectly modify arthropod food web interactions. As deer populations
      have increased in eastern North America over the past several decades, the
      effects of deer on web-building spiders may be widespread.

PMID- 27703866
TI  - Hypernasality associated with basal ganglia dysfunction: evidence from
      Parkinson's disease and Huntington's disease.
AB  - BACKGROUND: Although increased nasality can originate from basal ganglia
      dysfunction, data regarding hypernasality in Parkinson's disease (PD) and
      Huntington's disease (HD) are very sparse. The aim of the current study was to
      analyze acoustic and perceptual correlates of velopharyngeal seal closure in 37
      PD and 37 HD participants in comparison to 37 healthy control speakers. METHODS:
      Acoustical analysis was based on sustained phonation of the vowel /i/ and
      perceptual analysis was based on monologue. Perceptual analysis was performed by
      10 raters using The Great Ormond Street Speech Assessment '98. Acoustic
      parameters related to changes in a 1/3-octave band centered on 1 kHz were
      proposed to reflect nasality level and behavior through utterance. RESULTS:
      Perceptual analysis showed the occurrence of mild to moderate hypernasality in
      65% of PD, 89% of HD and 22% of control speakers. Based on acoustic analyses, 27%
      of PD, 54% of HD and 19% of control speakers showed an increased occurrence of
      hypernasality. In addition, 78% of HD patients demonstrated a high occurrence of
      intermittent hypernasality. Further results indicated relationships between the
      acoustic parameter representing fluctuation of nasality and perceptual assessment
      (r = 0.51, p < 0.001) as well as the Unified Huntington Disease Rating Scale
      chorea composite subscore (r = 0.42, p = 0.01). CONCLUSIONS: In conclusion the
      acoustic assessment showed that abnormal nasality was not a common feature of PD,
      whereas patients with HD manifested intermittent hypernasality associated with
      chorea.

PMID- 27703870
TI  - Intravitreal bevacizumab role in the treatment of macular edema secondary to
      retinal vasoproliferative tumor in a patient with neurofibromatosis type 1.
AB  - Objective: To report a case of neurofibromatosis-1 (NF-1) with retinal
      vasoproliferative tumor (RVPT) and macular edema and exudation that was
      successfully treated with intravitreal bevacizumab (IVB). Method: A retrospective
      case report of patient with neurofibromatosis, retinal vasoproliferative tumor
      and macular edema who received three monthly intravitreal injections of
      bevacizumab. Optical coherence tomography (OCT) and fluorescein angiography (FAG)
      before and three months after treatment were done. Results: Macular edema and
      exudation of the right eye was effectively resolved with IVB injection and
      vascularity of RVPT significantly decreased after treatment with IVB. Conclusion:
      Macular edema and exudation secondary to RVPT in patients with NF-1 could be
      successfully treated with IVB.

PMID- 27703871
TI  - Conjunctival lymphangioma in a 4-year-old girl revealed tuberous sclerosis
      complex.
AB  - Background: To present a case of conjunctival lymphangioma in a 4-year-old girl
      with tuberous sclerosis complex. Methods/results: A 4-year-old girl presented
      with a relapsing cystic lesion of the bulbar conjunctiva in the right eye with
      string-of-pearl-like dilation of lymphatic vessels and right-sided facial
      swelling with mild pain. Best-corrected vision was not impaired. Examination of
      the skin revealed three hypomelanotic macules and a lumbal Shagreen patch.
      Magnetic resonance imaging (MRI) findings displayed minimal enhancement of buccal
      fat on the right side. Cranial and orbital MRI showed signal enhancement in the
      right cortical and subcortical areas. Genetic analysis revealed a heterozygous
      deletion encompassing exon 1 and 2 of the TSC1 gene (tuberous sclerosis complex 1
      gene), confirming the diagnosis of tuberous sclerosis complex. Conclusion: In
      conjunctival lymphangioma, tuberous sclerosis complex should be considered as the
      primary disease.

PMID- 27703869
TI  - The complete chloroplast genome sequence of Gentiana lawrencei var. farreri
      (Gentianaceae) and comparative analysis with its congeneric species.
AB  - BACKGROUND: The chloroplast (cp) genome is useful in plant systematics, genetic
      diversity analysis, molecular identification and divergence dating. The genus
      Gentiana contains 362 species, but there are only two valuable complete cp
      genomes. The purpose of this study is to report the characterization of complete
      cp genome of G. lawrencei var. farreri, which is endemic to the Qinghai-Tibetan
      Plateau (QTP). METHODS: Using high throughput sequencing technology, we got the
      complete nucleotide sequence of the G. lawrencei var. farreri cp genome. The
      comparison analysis including genome difference and gene divergence was performed
      with its congeneric species G. straminea. The simple sequence repeats (SSRs) and
      phylogenetics were studied as well. RESULTS: The cp genome of G. lawrencei var.
      farreri is a circular molecule of 138,750 bp, containing a pair of 24,653 bp
      inverted repeats which are separated by small and large single-copy regions of
      11,365 and 78,082 bp, respectively. The cp genome contains 130 known genes,
      including 85 protein coding genes (PCGs), eight ribosomal RNA genes and 37 tRNA
      genes. Comparative analyses indicated that G. lawrencei var. farreri is 10,241 bp
      shorter than its congeneric species G. straminea. Four large gaps were detected
      that are responsible for 85% of the total sequence loss. Further detailed
      analyses revealed that 10 PCGs were included in the four gaps that encode nine
      NADH dehydrogenase subunits. The cp gene content, order and orientation are
      similar to those of its congeneric species, but with some variation among the
      PCGs. Three genes, ndhB, ndhF and clpP, have high nonsynonymous to synonymous
      values. There are 34 SSRs in the G. lawrencei var. farreri cp genome, of which 25
      are mononucleotide repeats: no dinucleotide repeats were detected. Comparison
      with the G. straminea cp genome indicated that five SSRs have length
      polymorphisms and 23 SSRs are species-specific. The phylogenetic analysis of 48
      PCGs from 12 Gentianales taxa cp genomes clearly identified three clades, which
      indicated the potential of cp genomes in phylogenetics. DISCUSSION: The "missing"
      sequence of G. lawrencei var. farreri mainly consistent of ndh genes which could
      be dispensable under chilling-stressed conditions in the QTP. The complete cp
      genome sequence of G. lawrencei var. farreri provides intragenic information that
      will contribute to genetic and phylogenetic research in the Gentianaceae.

PMID- 27703872
TI  - Management of implant plate exposure of silicone Ahmed glaucoma valve: a review
      of six cases.
AB  - Objective: To describe the management options for exposed silicone Ahmed glaucoma
      valve (AGV) implant. Methods: This was carried out as a retrospective chart
      review at a tertiary care eye hospital in Southern India. Medical records of six
      subjects managed for AGV exposure from 2006 to 2013 were reviewed. Results: All
      six eyes had explantation of the AGV and 3 of them had reimplantation in a
      different quadrant at a later date and the other 3 eyes were managed medically.
      All eyes had well controlled IOP at the last follow-up. The possible predisposing
      factors for exposure were improper conjunctival coverage, higher number of pre
      shunt surgeries and diabetes mellitus. Reimplantation was a challenge with
      scarred conjunctiva and the techniques used were conjunctival advancement,
      conjunctival relaxing incisions and contralateral conjunctival autograft. None
      had re-exposure but one eye had conjunctival erosion close to the limbus and was
      managed with scleral patch graft and conjunctival advancement. Conclusions:
      Implant exposure is a serious vision threatening complication following glaucoma
      drainage device implantation. Explantation and timely repair can save these eyes
      from serious sequel. Reimplantation is a good option, however warrants close
      follow-up for complications like erosion or re-exposure.

PMID- 27703873
TI  - Vitrectomy for bilateral macular schisis without apparent optic disc anomalies.
AB  - A 78-year-old man complained of bilateral visual acuity loss. Optical coherence
      tomography examination showed bilateral macular schisis with fluid accumulation
      in the external retinal layers without vitreous traction. Fundus examination and
      fluorescein angiography were normal in both eyes. Both eyes were treated by
      phacoemulsification, intraocular lens implantation, and vitrectomy without laser,
      gas exchange, or retinal fenestration. Slow and progressive fluid resorption and
      improvement in VA were observed in both eyes. Macular schisis similar to the one
      associated with optic disc anomalies is a possibility in patients without
      apparent disc anomalies. Vitrectomy without laser, gas, or retinal fenestration
      may be a good therapeutic option even in patients with a PVD preoperatively.

PMID- 27703874
TI  - Avoiding Sand in the Desert.

PMID- 27703875
TI  - What Counts as High-Quality Practitioner Training in Applied Behavior Analysis?
AB  - Dixon and colleagues (this issue), who support faculty research productivity as
      one measure of quality for graduate training programs in applied behavior
      analysis, show that the faculty members of many programs have limited research
      track records. I provide some context for their findings by discussing some of
      the many unanswered questions about the role of research training for ABA
      practitioners.

PMID- 27703876
TI  - Research Rankings of Behavior Analytic Graduate Training Programs and Their
      Faculty.
AB  - We evaluated research productivity of several graduate programs that provide
      Behavior Analyst Certification Board (BACB)-approved course sequences in behavior
      analysis. Considering the faculty of BACB training programs as a unit, in only
      about 50 %, programs have faculty combined to publish ten or more total articles
      in our field's primary empirical journals. Among individual faculty members, a
      sizeable number have not published an article in any of the field's top journals.
      To recognize major scholarly contributors, we provide top 10 lists of training
      programs and individual faculty members. We conclude by discussing the importance
      of research in an increasingly practice-driven marketplace.

PMID- 27703877
TI  - A Survey of Staff Training and Performance Management Practices: the Good, the
      Bad, and the Ugly.
AB  - The costs for delivering services to individuals with autism and other
      disabilities total more than $137 billion annually and grow exponentially. Given
      this figure, service-delivery organizations are under pressure to ensure staff
      are well-prepared to deliver services through the provision of training.
      Providing effective staff training and performance management is also necessary
      for the delivery of evidence-based practice and is an ethical obligation for
      Behavior Analyst Certification Board(r), Inc. (BACB(r)) certificants. The purpose
      of the present study was to document the various types of staff and supervisory
      training and performance management procedures offered to BACB(r) certificants
      and aspirants working in applied settings.

PMID- 27703878
TI  - Evaluating the Relationship Between Sleep and Problem Behavior in Children with
      Disabilities.

PMID- 27703879
TI  - Global Measures of Treatment Integrity May Mask Important Errors in Discrete
      Trial Training.

PMID- 27703880
TI  - Latency-Based FA as Baseline for Subsequent Treatment Evaluation.
AB  - No research has used latency-based functional analysis (FA) outcomes as baseline
      data from which to evaluate the effectiveness of subsequent function-based
      treatments. This approach to analysis calls for the continued collection of
      latency-based measures for all targeted variables throughout all phases of
      treatment. We tracked client progress during treatment using latency-based, rate
      based, and percentage-of-opportunity measures of relevant behavior and compared
      graphical representations of each. Visual inspection of all data indicates that
      changes in variability level and trend of latency-based measures correspond well
      with said changes in more traditional measures.

PMID- 27703881
TI  - Implications of Derived Rule Following of Roulette Gambling for Clinical
      Practice.
AB  - Problem gambling is a global concern, and behavior analytic attention has
      increasingly focused on reasons for why problem gambling occurs and conditions
      under which it is maintained. However, limited knowledge currently exists on the
      process to which self-generated rules maintain gambling behaviors. Therefore, the
      current study assessed six recreational gamblers on a roulette game before and
      after discrimination training to establish a self-rule to wager on red or black.
      Following discrimination training, all six participants altered their response
      allocation among red or black and consistently responded according to the newly
      derived self-rule. Results maintained during 1-week follow-up sessions across all
      participants. Implications for clinical application of self-awareness and self
      generated rule following are discussed. Implications for practice * Demonstration
      of how stimuli such as color can alter gambling behavior * Procedures to assist
      clients with changing self-rules about gambling behavior * Using self-generated
      rule formulation for more contextually appropriate target behaviors * Highlights
      how self-generated rules can be altered to change clinical target behaviors.

PMID- 27703882
TI  - Exploring the Clinical Utility of a Stimulus Avoidance Assessment to Enhance a
      Relaxation Training Model.
AB  - The current case study explored the clinical utility of a stimulus avoidance
      assessment during relaxation training with an adult with an autism spectrum
      disorder. A multiple stimulus without replacement procedure was implemented with
      aversive events to identify an aversive situation hierarchy. Aversive events were
      then systematically presented during the analogue phase of relaxation training
      across low, medium, and highly aversive events. Results support a clinical
      utility of using stimulus assessments to inform relaxation training, while
      suggesting further modifications to relaxation training protocols for
      generalization of skills.

PMID- 27703883
TI  - Applied Behavior Analysis and the Autism Diagnostic Observation Schedule (ADOS):
      a Symbiotic Relationship for Advancements in Services for Individuals with Autism
      Spectrum Disorders (ASDs).
AB  - The Autism Diagnostic Observation Schedule (ADOS) is a widely used diagnostic
      tool for the assessment of autism spectrum disorders. We compared interobserver
      reliability scores for observers using the existing guidelines for administration
      of the ADOS with those of the same observers using modified guidelines that
      included operational definitions for each area of observation. The results
      indicated increased mean interobserver reliability scores from 55.83 % using the
      existing guidelines to 84 % when using the modified guidelines and enhanced
      reliability scores for 3 of 3 clients with whom the ADOS was used. The guidelines
      are the following: integration of a highly effective diagnostic tool with ABA,
      the inclusion of a diagnostic tool may promote more comprehensive ABA services,
      more clearly define and identify areas of concern in autism, and impact
      implementation efficacy and reliability of assessments for individuals with
      autism.

PMID- 27703884
TI  - Effects of a Preferred Stimulus and Mother's Attention on Infant Behavior During
      Tummy Time.
AB  - "Tummy time" is an activity for infants to develop muscle tone; however, it often
      evokes crying and non-compliance. The current study investigated two
      interventions for an infant to a) increase elevated head behavior, and b)
      decrease negative vocalizations. The study compared the effects of a preferred
      stimulus with or without maternal attention on infant behaviors during tummy
      time. The addition of maternal attention produced more positive outcomes:The
      science of behavior analysis can be used to treat a broad range of socially
      significant behaviors like infant behavior during tummy time.Preference
      assessments can be used with infants to identify potentially reinforcing
      stimuli.The continuous provision of a preferred stimulus during tummy time may
      help infants to increase positive behaviors and decrease problem behaviors.Parent
      attention may have an added benefit to a treatment package for typically
      developing infants.

PMID- 27703885
TI  - Maintaining Professional Relationships in an Interdisciplinary Setting:
      Strategies for Navigating Nonbehavioral Treatment Recommendations for Individuals
      with Autism.
AB  - Due to an increase in research and clinical application of behavior analysis with
      individuals with autism spectrum disorder (ASD), one setting a Board Certified
      Behavior Analyst (BCBA) may work within is an interdisciplinary setting, where
      multiple disciplines collaborate to improve the outcomes of individuals with ASD.
      In some cases, nonbehavioral colleagues could recommend nonbehavioral treatments,
      setting the occasion for the BCBA to offer an alternative treatment to or
      question the nonbehavioral treatment. However, excessive questioning or critiques
      of nonbehavioral treatments by the BCBA may unintentionally erode professional
      relationships between the BCBA and their nonbehavioral colleagues. Because an
      erosion of professional relationships may occur when a BCBA questions a
      nonbehavioral treatment, a decision-making model for determining whether or not
      the proposed nonbehavioral treatment is worth addressing may be useful. The
      purpose of this paper is to outline such a decision-making model in order to
      assist the BCBA in assessing nonbehavioral treatments while maintaining an
      ethical balance between professional relationships and the well-being and safety
      of the individual with ASD. Such a model could assist the BCBA in becoming
      familiar with the proposed treatment, understanding the perspective of the
      nonbehavioral colleague and assessing the negative impacts the treatment could
      have on the individual with ASD. With this information, the BCBA will be in a
      better position to decide whether or not addressing the nonbehavioral treatment
      is worth the possibility of eroding a professional relationship.

PMID- 27703886
TI  - In Response: Maintaining Professional Relationships in an Interdisciplinary
      Setting: Strategies for Navigating Non-behavioral Treatment Recommendations for
      Individuals with Autism.

PMID- 27703887
TI  - School-wide PBIS: An Example of Applied Behavior Analysis Implemented at a Scale
      of Social Importance.
AB  - School-wide Positive Behavioral Interventions and Supports (PBIS) is an example
      of applied behavior analysis implemented at a scale of social importance. In this
      paper, PBIS is defined and the contributions of behavior analysis in shaping both
      the content and implementation of PBIS are reviewed. Specific lessons learned
      from implementation of PBIS over the past 20 years are summarized.

PMID- 27703888
TI  - Positive Behavioral Interventions and Support as Behavior Analysis in Practice:
      Why Is This Even Controversial?
AB  - The inclusion of Positive Behavioral Intervention and Supports as a type of
      applied behavior analysis has often spurred considerable controversy. This
      controversy seems related to at least three areas of contention: measurement
      issues, views on aversive control, and the overall target of treatment. The
      present paper discusses these three areas in light of Horner and Sugai's target
      article and the current state of the field of applied behavior analysis. In the
      end, the authors are left wondering why this is even an ongoing controversy.

PMID- 27703889
TI  - School-Wide PBIS: Extending the Impact of Applied Behavior Analysis. Why is This
      Important to Behavior Analysts?
AB  - Horner and Sugai (2015) recently wrote a manuscript providing an overview of
      school-wide positive behavioral interventions and supports (PBIS) and why it is
      an example of applied behavior analysis at the scale of social importance. This
      paper will describe why school-wide PBIS is important to behavior analysts, how
      it helps promote applied behavior analysis in schools and other organizations,
      and how behavior analysts can use this framework to assist them in the promotion
      and implementation of applied behavior analysis at both at the school and
      organizational level, as well as, the classroom and individual level.

PMID- 27703890
TI  - A Critique of Sociocultural Values in PBIS.
AB  - Horner and Sugai provide lessons learned from their work with disseminating the
      Positive Behavioral Interventions and Support (PBIS) model. While PBIS represents
      an empirical school-wide approach for maladaptive student behaviors, the model
      appears to have limitations regarding sociocultural values and behavioral data
      collection practices. The current paper provides an overview of three identified
      areas for improvement and outlines how administrators using PBIS can incorporate
      acceptance and mindfulness-based intervention procedures to address the discussed
      limitations.

PMID- 27703891
TI  - PBIS Is (Not) Behavior Analysis: a Response to Horner and Sugai (2015).
AB  - I comment on Horner's and Sugai's article regarding the lessons learned from
      implementing Positive Behavioral Interventions and Support (PBIS)-that is, the
      things to consider when attempting to extend other works in behavior analysis to
      the likes of mainstream society. In adopting a critical eye toward the PBIS
      model, I comment first on the need for dissemination of behavioral principles to
      a public audience, and then outline the suggestions made by the authors for
      enhancing acceptance across disciplines. I clarify the definition of PBIS
      presented by the authors, and summarize the benefits and drawbacks associated
      with the conceptual argument surrounding the contention that PBIS is a behavior
      analytic approach to system-wide change, and argue instead for the distinction of
      elements in the PBIS model and their respective empirical effectiveness. I refer
      to other works in behavior analysis that are relevant to the current discussion
      and offer additional considerations for behavior analysts interested in forging
      ahead with endeavors that aim increase dissemination, particularly those that
      incorporate a culmination of alternative professional practices.

PMID- 27703892
TI  - PBIS May Not Qualify as Classical Applied Behavior Analysis. So What?
AB  - Some disagreement exists over whether Positive Behavior Interventions and
      Supports (PBIS) embodies the features of Applied Behavior Analysis (ABA) as
      described in a classic 1968 paper by Baer, Wolf, and Risley. When it comes to
      disseminating interventions at a societal level, a more compelling issue is
      whether ABA should become more like PBIS.

PMID- 27703893
TI  - Positive Behavior Support for Individuals with Behavior Challenges.
AB  - Individual positive behavior support (PBS) is a process that combines evidence
      based practices from applied behavior analysis (ABA) and other disciplines to
      resolve behavioral challenges and improve independence, participation, and
      overall quality of life of individuals living and learning in complex community
      environments. Its features include lifestyle enhancement, collaboration with
      typical caregivers, tracking progress via meaningful measures, comprehensive
      function-based interventions, striving for contextual fit, and ensuring buy-in
      and implementation. This article will summarize the features and illustrate with
      a case example. * Engaging caregivers to take an active role in behavioral
      intervention * Designing interventions that work effectively within natural
      routines * Addressing lifestyle changes, as well as more discrete behavior
      changes * Creating strategies that are durable, reducing dependence on
      professionals.

PMID- 27703894
TI  - Ask the Experts: Answer to: How Can New Students Defend Behavior Analysis from
      Misunderstandings?
AB  - This is a response to the Ask the Experts question regarding whether students in
      behavior analysis programs should respond to misrepresentations made by others
      about the field.

PMID- 27703895
TI  - Training Graduate Students to Effectively Disseminate Behavior Analysis and to
      Counter Misrepresentations.
AB  - Training graduate students to promote behavior analysis and counter
      misconceptions requires that graduate programs in behavior analysis contain a
      healthy dose of experimental analysis of behavior so that students understand the
      experimental foundations of their discipline. Moreover, graduate students should
      be required to study the theoretical and philosophical foundations of the field
      because most of the misconceptions of behavior analysis are conceptual and
      philosophical in nature. Programs should also teach graduate ABA students to
      think critically about the concepts and principles of behavior analysis in order
      to prepare them to defend it against misunderstandings and to be more effective
      practitioners.

PMID- 27703896
TI  - The Experts Have Spoken!: A Reply to Four Commentaries.
AB  - Four prominent behavior analysts provided advice to graduate students when
      attempting to correct misunderstandings about behavior analysis. This article
      briefly summarizes the four commentaries.

PMID- 27703897
TI  - Field Report: Beyond the Dog.

PMID- 27703898
TI  - Field Report: Autism Partnership.

PMID- 27703899
TI  - Perspectives on the Field of Behavior Analysis.

PMID- 27703901
TI  - There's a Man Goin' Round Taking Names.
AB  - This commentary addresses the two basic premises of the argument made by Dixon et
      al (2015) concerning quality metrics for behavior analytic graduate training
      programs. Taken together, these premises assert that the practice of behavior
      analysis will be more effective if practitioners are research savvy and that
      becoming research savvy is more likely to occur in a circumstance in which
      research is ongoing. I support both of these assumptions, the former by examining
      the impact of group circumstances on values, and the latter by considering the
      repertorial elements likely to be established under conditions of contingency
      shaping.

PMID- 27703900
TI  - In Dreams Begin Responsibility: Why and How to Measure the Quality of Graduate
      Training in Applied Behavior Analysis.
AB  - Although no one knows just how effective graduate training may be in creating
      effective practitioners of applied behavior analysis, there are plenty of logical
      and historical reasons to think that not all practitioners are equally competent.
      I detail some of those reasons and explain why practitioner effectiveness may be
      a more pressing worry now than in the past. Because ineffective practitioners
      harm the profession, rigorous mechanisms are needed for evaluating graduate
      training programs in terms of the field effectiveness of their practitioners.
      Accountability of this nature, while difficult to arrange, would make applied
      behavior analysis nearly unique among professions, would complement existing
      quality control processes, and would help to protect the positive reputation and
      vigorous consumer demand that the profession currently enjoys.

PMID- 27703902
TI  - Metrics of Quality in Graduate Training.
AB  - This commentary, in response to Dixon et al. (Behavior Analysis in Practice, 8, 7
      15, 2015), describes difficulties in defining metrics of quality in graduate
      training for different audiences (types of applicants). Outcome measures are
      preferred whenever possible, supplemented by subjective but frequently used
      opinion surveys.

PMID- 27703903
TI  - My Heroes Have Always Been Cowboys.

PMID- 27703904
TI  - Icing on the Cake: The Role of Research in Practitioner Training.
AB  - Dixon, Reed, Smith, Belisle, and Jackson (Behavior Analysis in Practice 8, 7-15,
      2015) evaluated research productivity in BACB training programs. While research
      productivity may indeed be an important metric for future researchers, we posit
      that the field consists mainly of practitioners, and as such training should be
      focused on practice. We provide an alternative perspective on enhancing the
      quality of education for behavior analysts who will, by and large, go on to be
      practitioners.

PMID- 27703905
TI  - Expanding the Scope of Research Productivity Indices: a Commentary on Dixon,
      Reed, Smith, Belisle, and Jackson (2015).
AB  - Dixon et al. (Behavior Analysis in Practice, 8:7-15, 2015) outlined methods to
      evaluate research rankings of behavior analytic graduate training programs and
      their graduate faculty. Publications across five behavior analytic journals were
      evaluated and cumulative totals were obtained for each program and its faculty
      members. Critchfield (Behavior Analysis in Practice, 8:3-6, 2015) noted that
      these measures indicated that many graduate students in behavior analysis are
      receiving training by faculty members with limited research productivity. This
      commentary offers some suggestions and refinements of the procedures used by
      Dixon et al. that might provide a more sensitive measure of scholarly
      productivity in our field. The implications of these suggestions are discussed.

PMID- 27703907
TI  - The Emperor Just Might Be Wearing Pants.
AB  - This is a commentary in response to Dixon et al.'s (Behavior Analysis and
      Practice, 8(1), 7-15, 2015) article entitled, "Research rankings of behavior
      analytic graduate training programs and their faculty" in Behavior Analysis in
      Practice. The severe restriction of range for the metric used to identify faculty
      productivity and knowledge of research calls the implications drawn from the data
      into question. Suggestions on how to broaden the metric are made along with
      implications for doing so. This is an important topic, and many people will need
      to contribute to a robust conversation about our graduate training programs given
      the exponential growth we have faced in recent decades.

PMID- 27703906
TI  - Are We Looking for Love in All the Wrong Places? Comment on Dixon et al.
AB  - Dixon and colleagues (Behavior Analysis in Practice 8(1):7-15, 2015) used
      publication rates of faculty in programs with Behavior Analyst Certification
      Board (BACB) approved course sequences as a proxy measure for the quality of the
      program. The paper is important because it begins a conversation about what the
      characteristics of a quality program should be. Low publication rates for most of
      these programs and their faculties were a source of concern for Dixon, et al.,
      but from the perspective of measurement validity, this finding is not necessarily
      bad news. Program quality is a multi-dimensional construct, and for some
      dimensions, publication rates are likely to be irrelevant.

PMID- 27703908
TI  - Evaluating the Quality of Behavior Analytic Practitioner Training Programs.
AB  - Dixon and colleagues (2015) asserted that faculty research productivity is a key
      indicator of the quality of university programs that train future practitioners
      of behavior analysis. Based on their analysis of publications in select journals,
      the authors concluded that many faculty in such programs have published little to
      no research. Some alternative measures of both faculty research productivity and
      the quality of practitioner training programs are suggested here.

PMID- 27703909
TI  - The Importance of Research-A Student Perspective.
AB  - As students, we will focus on the importance of an objective ranking system,
      research, and mentorship to an applicant. We will address points raised in the
      (Behavior Analysis In Practice 8(1):7-15, 2015) article as well as debate the
      usefulness of proposed standards of objective ranking.

PMID- 27703910
TI  - Another Perspective on Research as a Measure of High-Quality Practitioner
      Training: a Response to Dixon, Reed, Smith, Belisle, and Jackson.
AB  - Dixon et al. (Behavior Analysis in Practice 8:7-15, 2015) argued that the
      research productivity of behavior analytic graduate programs may be a reasonable
      criterion to evaluate training program quality. They reviewed the cumulative
      publications of graduate programs. From this analysis, they generated a top ten
      list of graduate programs with the greatest number of faculty publications and,
      because of the number of these publications, inferred that they may be better
      training programs than those not on the list. We countered that the quality of
      graduate training programs is evident in the behavior of those who are trained,
      and thus, our field's interest should focus on determining the degree to which
      individual program graduates-and not their faculty-have mastered the research
      process. Thus, we proposed including student authors' work as an alternative to
      Dixon et al.'s analysis.

PMID- 27703912
TI  - An Alternative Strategy for Selecting a Graduate Program: Comments on Dixon et
      al. (2015).
AB  - While the rankings based upon frequencies of publication, supplied by Dixon et
      al. (2015), identify individuals and programs worthy of prospective students'
      attention, I have focused upon other criteria when mentoring students who are
      deciding where to apply for graduate study. Those criteria concern the student's
      particular interests, and questions concerning what it is like to work with a
      given mentor or within a given program. Besides perusals of web sites and queries
      directed to prospective mentors, students already working with that mentor can
      provide valuable information. Provision for hands-on training in the application
      of behavioral principles is essential to a high-quality program, and availability
      of conceptually oriented courses and of a supportive verbal community are
      additional considerations, especially if a mentor is not frequently available for
      informal conversation. As alternatives, the Behavior Analysis Certification
      Board's credential has the limitations of any multiple-choice examination as an
      evaluation of hands-on competence, and the accreditation of programs by the
      Association for Behavior Analysis International omits many mentorships that have
      trained outstanding behavior analysts via "apprenticeships" within programs that
      are not primarily behavior analytic.

PMID- 27703911
TI  - An Alternative Measure of Research Productivity Among Behavior Analytic Graduate
      Training Programs: a Response to Dixon et al. (2015).

PMID- 27703913
TI  - Doing It Yourself.

PMID- 27703915
TI  - Top 10 Responses to the Commentaries on Dixon, Reed, Smith et al. (2015).
AB  - In a previous article (Dixon et al. Behavior Analysis in Practice, 8(1), 7-15,
      2015), we put forward data suggesting that most behavior analytic faculty do not
      publish in major behavior analytic journals, and in only about 50 % of behavior
      analysis programs have faculty combined to produce ten or more empirical
      articles. Several commentaries followed the release of our article, with content
      that ranged from supporting our endeavors and confirming the dangerous position
      our field may be in to highlighting the need for further refinement in procedures
      used to rank the quality of behavior analysis graduate training programs.
      Presented in the present article are our "top 10" responses to these
      commentaries.

PMID- 27703914
TI  - On the Complexity of Correlating a Graduate Program's Experiences with the
      Success of its Graduates: a Response to Dixon et al. (2015).
AB  - Dixon et al. Behavior Analysis in Practice 8:7-15, 2015 evaluated the scholarly
      productivity of instructors in graduate-level, behavior-analytic training
      environments as a potential quality metric related to practitioner training. In
      our reply, we discuss the authors' premise and methodology, suggest alternative
      conceptualizations, and recommend a more comprehensive and germane approach to
      the task.

PMID- 27703916
TI  - Social Validity Assessment of Physical Restraint Intervention by Care Providers
      of Adults with Intellectual and Developmental Disabilities.

PMID- 27703917
TI  - Digital Communication and Records in Service Provision and Supervision:
      Regulation and Practice.
AB  - While the use of computer-based communication, video recordings, and other
      "electronic" records is commonplace in clinical service settings and research,
      management of digital records can become a great burden from both practical and
      regulatory perspectives. Three types of challenges commonly present themselves:
      regulatory requirements; storage, transmission, and access; and analysis for
      clinical and research decision-making. Unfortunately, few practitioners and
      organizations are well enough informed to set necessary policies and procedures
      in an effective, comprehensive manner. The three challenges are addressed using a
      demonstrative example of policies and procedural guidelines from an applied
      perspective, maintaining the unique emphasis behavior analysts place upon
      quantitative analysis. Specifically, we provide a brief review of federal
      requirements relevant to the use of video and electronic records in the USA; non
      jargon pragmatic solutions to managing and storing video and electronic records;
      and last, specific methodologies to facilitate extraction of quantitative
      information in a cost-effective manner.

PMID- 27703918
TI  - Guidelines for Developing Telehealth Services and Troubleshooting Problems with
      Telehealth Technology When Coaching Parents to Conduct Functional Analyses and
      Functional Communication Training in Their Homes.
AB  - The researchers in the project used telehealth to conduct functional analyses and
      functional communication training in homes of children diagnosed with autism who
      displayed problem behavior. Parents conducted all assessment and treatment
      procedures within their homes while receiving coaching from applied behavior
      analysts located approximately 200 miles away from them. In this article, the
      researchers summarize the technical systems they used to develop a telehealth
      service and the concerns and problems they have encountered using telehealth and
      provide some guidelines for how to troubleshoot those problems.

PMID- 27703919
TI  - Research Productivity Among Practitioners in Behavior Analysis: Recommendations
      from the Prolific.

PMID- 27703920
TI  - Inserting Phase Change Lines into Microsoft Excel(r) Graphs.
AB  - Microsoft Excel(r) is a popular graphing tool used by behavior analysts to
      visually display data. However, this program is not always friendly to the
      graphing conventions used by behavior analysts. For example, adding phase change
      lines has typically been a cumbersome process involving the insertion of line
      objects that do not move when new data is added to a graph. The purpose of this
      article is to describe a novel way to add phase change lines that move when new
      data is added and when graphs are resized.

PMID- 27703921
TI  - Escape Extinction and Negative Reinforcement in the Treatment of Pediatric
      Feeding Disorders: a Single Case Analysis.
AB  - Pediatric feeding disorders are common among children with developmental
      disabilities and can have detrimental effects on growth and development. An
      escape extinction and negative reinforcement-based approach to treating food
      refusal was examined in a child with cerebral palsy. A changing criterion
      treatment design was implemented, which allowed the child to exit the treatment
      area contingent upon the acceptance and ingestion of a pre-determined number of
      bites. Food acceptance ranged from one to three bites at baseline and exceeded
      the pre-set criteria for mastery, at 14 bites during the final intervention
      phase.The study will contribute to the current literature on negative
      reinforcement procedures used in the treatment of pediatric feeding problems.The
      study will contribute to increasing the availability of literature pertaining to
      pediatric feeding problems among children with complex disabilities such as
      cerebral palsy.The intervention is brief with components to the treatment package
      which increases utility and ease of implementation.The study demonstrates the
      applicability of changing criterion design within clinical settings.

PMID- 27703922
TI  - Blending Stimulus Fading Procedures with Forward Chaining to Address Treatment
      Resistance in an Adult with an Autism Spectrum Disorder.
AB  - The following paper details the implementation of a program to address the high
      risk physical aggression and property destruction behavior of an adult male with
      an autism spectrum disorder (ASD) and severe aggressive behavior. A task analysis
      (TA) and forward chaining were combined with a stimulus fading procedure to allow
      the subject to be able to participate in van rides when prompted with no displays
      of aggressive or self-injurious behavior. A follow-up probe completed at 1-year
      post intervention demonstrated the maintenance of the gains that were made during
      treatment.

PMID- 27703924
TI  - Inducing Novel Vocalizations by Conditioning Speech Sounds as Reinforcers.
AB  - Automatic reinforcement by response-produced auditory stimuli has long been
      hypothesized to play a role in the vocal development of infants. Clinicians and
      researchers have translated this idea into stimulus pairing interventions
      intended to increase novel vocalizations of nonverbal children with autism and
      other developmental disabilities by conditioning speech sounds as reinforcers. A
      number of studies have demonstrated positive effects of stimulus pairing
      procedures, but negative results have also been reported in the literature. This
      article provides a brief review of the existing literature on stimulus pairing
      procedures and a discussion of alternative procedures that may serve to establish
      speech sounds as reinforcers. Directions for future research are discussed and
      recommendations provided to clinicians.

PMID- 27703923
TI  - A Comparison of Feedback Provided In Vivo Versus an Online Platform on the
      Treatment Integrity of Staff Working with Children with Autism.
AB  - The number of BACB-accredited distance education programs is increasing,
      potentially bringing remote supervision into greater demand. Videoconferencing
      programs like SkypeTM represent one avenue for remote supervision. The current
      study compares the effects of covert observations, in vivo observations, and
      observations using the SkypeTM program on treatment integrity in three therapists
      working with children diagnosed with autism. The results show that the level of
      treatment integrity is comparable in both the in vivo and SkypeTM conditions,
      both of which are superior to the covert observation condition.

PMID- 27703925
TI  - Using Graduated Exposure and Differential Reinforcement to Increase Food
      Repertoire in a Child with Autism.
AB  - Food selectivity is often seen in children with autism spectrum disorder and can
      lead to severe nutritional deficiencies. Food selectivity can be specific to food
      texture, colour, shape, presentation, type, brand or container. Often food
      selectivity is treated using escape extinction in conjunction with other
      procedures, which can be challenging to implement for the therapist or caregiver,
      aversive for the child, and requires adequate supervision from a professional to
      ensure fidelity of the procedure. A preference assessment, parent interview and
      food journal determined the child's food repertoire consisted of four different
      foods in total (pasta, fish crackers, dry cereal and yogurt), and the child was
      selective by brand, texture, temperature and utensil requirement. A 12-step
      graduated exposure food hierarchy was constructed, the child was lead through the
      hierarchy, and parent training was implemented for generalization. After 9 months
      of treatment, the participant's food repertoire increased from four items to more
      than 50 items. Additionally, food refusal behaviour decreased to rates of zero
      during intervention and parents report significant decreases in mealtime
      behaviour at home. The importance of using an alternative strategy to escape
      extinction for treating food selectivity in children with autism spectrum
      disorder will be discussed.

PMID- 27703926
TI  - Teaching Complex Verbal Operants with the PEAK Relational Training System.
AB  - The present study evaluated the effectiveness of five packaged protocols from the
      Promoting the Emergence of Advanced Knowledge (PEAK) curriculum. The skills
      targeted in the study included complex verbal operants proposed by Skinner
      (Verbal behavior. Englewood Cliffs, NJ: Prentice Hall, 1957), an area that is
      lacking in the current literature. The target skills included autoclitics,
      metonymical tacts, tacting planet names, and guessing. The results suggest that
      the PEAK methodology was effective in teaching each of the targeted skills to a
      mastery criterion, as well as maintenance of those skills at a 2-week follow-up
      phase.

PMID- 27703928
TI  - Infected shoulder joint with loose Suture Anchor in the joint after Bankart's
      Repair- A Case Report.
AB  - INTRODUCTION: The glenoid labrum is frequently torn in traumatic glenohumeral
      dislocation; arthroscopic repair is the standard method of treatment. The
      complications associated with this repair are pulling out of metal suture
      anchors, chondrolysis and joint infection. The infection of joint after
      arthroscopy is less than 1%. Staphylococcus is most common organism and rarely
      followed by Pseudomonas aeruginosa. We report a case of infected shoulder with
      chondrolysis of the joint and pulled out metal suture anchor lying inside the
      joint after Bankart's repair. CASE REPORT: A 22-year-old gentleman came to us
      with complaints of shoulder joint pain & gross restriction of movements for one
      year, with history of intermittent fever and treatment in nearby hospital. He
      also gives past history of recurrent dislocation of shoulder with last episode 18
      months back, which was diagnosed as Bankart's lesion and arthroscopic Bankart's
      repair was done 15 months back. He was evaluated at our institute and suspected
      to have infection of shoulder joint with pulled out metal suture anchor inside
      the joint. Arthroscopic removal of suture anchor and debridement of shoulder
      joint was done, Culture was obtained and culture specific antibiotics were given
      for six weeks, and significant improvement was observed with this line of
      treatment. At lyear follow up, the patient was able to perform his daily
      activities with terminal restriction of range of motion. CONCLUSIONS: Shoulder
      joint infection is rare after Bankart's repair and required a high degree of
      suspicion. Any foreign materials inside the joint should be taken out & followed
      with aggressive treatment by debridement, irrigation and culture specific
      antibiotics. Suppression of joint infection with antibiotics should be avoided
      specially when there is foreign body inside the joint.

PMID- 27703929
TI  - Dedifferentiated Chondrosarcoma of Proximal Tibia and Fibula with an Infected
      Ulcer: A Case Report.
AB  - INTRODUCTION: Dedifferentiated chondrosarcoma (DDCS) is a rare and malignant form
      of primary bone tumor refractive to chemotherapy and radiotherapy. It accounts
      for 1-2% of all primary bone tumors. Surgical resection, limb-salvage surgeries
      and amputation remain the mainstay of treatment. The prognosis of
      dedifferentiated chondrosarcoma is poor. CASE REPORT: We report a case of a 51
      year-old male having a swelling and an ulcer distal to the left knee later
      diagnosed with dedifferentiated chondrosarcoma of proximal tibial and fibular
      metaphysis. Although DDCS is a highly malignant tumor, no metastasis was found
      and the patient was treated with transfemoral amputation. Post-operative
      histopathology showed nuclear atypia, binucleated and multinucleated chondrocytes
      with spindling and neoplastic cells arranged in storiform pattern and giant cells
      which confirmed the diagnosis of DDCS. CONCLUSION: Early diagnoses and treatment
      are important while treating these tumors in order to prevent morbidity and
      mortality.

PMID- 27703927
TI  - Genome-Wide Anaplasma phagocytophilum AnkA-DNA Interactions Are Enriched in
      Intergenic Regions and Gene Promoters and Correlate with Infection-Induced
      Differential Gene Expression.
AB  - Anaplasma phagocytophilum, an obligate intracellular prokaryote, infects
      neutrophils, and alters cardinal functions via reprogrammed transcription. Large
      contiguous regions of neutrophil chromosomes are differentially expressed during
      infection. Secreted A. phagocytophilum effector AnkA transits into the neutrophil
      or granulocyte nucleus to complex with DNA in heterochromatin across all
      chromosomes. AnkA binds to gene promoters to dampen cis-transcription and also
      has features of matrix attachment region (MAR)-binding proteins that regulate
      three-dimensional chromatin architecture and coordinate transcriptional programs
      encoded in topologically-associated chromatin domains. We hypothesize that
      identification of additional AnkA binding sites will better delineate how A.
      phagocytophilum infection results in reprogramming of the neutrophil genome.
      Using AnkA-binding ChIP-seq, we showed that AnkA binds broadly throughout all
      chromosomes in a reproducible pattern, especially at: (i) intergenic regions
      predicted to be MARs; (ii) within predicted lamina-associated domains; and (iii)
      at promoters <= 3000 bp upstream of transcriptional start sites. These findings
      provide genome-wide support for AnkA as a regulator of cis-gene transcription.
      Moreover, the dominant mark of AnkA in distal intergenic regions known to be AT
      enriched, coupled with frequent enrichment in the nuclear lamina, provides strong
      support for its role as a MAR-binding protein and genome "re-organizer." AnkA
      must be considered a prime candidate to promote neutrophil reprogramming and
      subsequent functional changes that belie improved microbial fitness and
      pathogenicity.

PMID- 27703930
TI  - Case Report of Two Cases of Patella Subacute Osteomyelitis in Diabetic Women A
      Rare Entity.
AB  - INTRODUCTION: Patella osteomyelitis is a rare entity in adults. Most often it is
      seen in children of five to twelve years of age because of its unique
      ossification and vascularity. Immuno compromised states like HIV, tuberculosis,
      intravenous drug abuse and trauma have been predisposing factors for adult
      patellar osteomyelitis. We report two cases of patellar osteomyelitis in adult
      diabetic women with uncontrolled glycemic levels and having no previous history
      of any trauma or systemic infection. CASE REPORT: A 43-year-old diabetic woman
      presented with complaints of left knee pain and swelling with no history of
      trauma. On examination, pointed tenderness was present over anterior aspect of
      patella with patellar grind test positive. Radiography and MRI revealed solitary
      well circumscribed patellar cyst. Lateral chondral blisters were noted while
      doing arthroscopy and secretions oozed out on puncturing. Curettage was carried
      out for the same. Culture and sensitivity revealed no growth and the patient was
      prescribed antibiotics for 6 weeks. Second case was a 46-year-old diabetic lady
      with similar presentation. MRI additionally showed abscess in intermuscular
      plains around knee joint. An aspirated fluid was negative for growth of
      organisms. Knee arthrotomy and curettage of patellar sinus tracts was done with
      evacuation of intramuscular abscess. Antibiotics were given for 6 weeks. Both
      patients had complete relief of symptoms. CONCLUSION: Patella osteomyelitis in
      adults is very rare. In patients with uncontrolled diabetes, vague anterior knee
      pain, elevated ESR and CRP, one should keep patellar subacute osteomyelitis as a
      differential diagnosis which can be further confirmed by X-ray, MRI or bone scan.
      An appropriate early treatment with antibiotics and surgical intervention can
      give a satisfactory result.

PMID- 27703931
TI  - Retrocalcaneal Bursitis due to Rare Calcaneal Osteochondroma in Adult Male :
      Excision and Outcome.
AB  - INTRODUCTION: Osteochondroma is the most common benign tumour of the bone and is
      considered as developmental lesion of the bone. Common site of osteochondroma
      presentation is around the knee but calcaneal osteochondroma as such is a rare
      entity. Osteochondromas grow during childhood through adolescence, but usually
      the growth of osteochondroma ends when the epiphyseal plates close. In an adult,
      growth of an osteochondroma suggests the diagnosis of a malignant transformation.
      However, it can also present as pressure symptom in later phase of life. Here, we
      presented a case of retrocalcaneal bursitis in late phase of life of a male
      farmer due to late growth of osteochondroma. CASE PRESENTATION: We report a case
      of calcaneal osteochondroma which is an extremely rare site of occurrence with
      painful swelling of ankle causing limitation of walking in a 58-year-old male.
      Surgical excision of tumour followed by a histological confirmation reported
      negative for any malignant changes. CONCLUSION: There may be chances of
      osteochondroma being a reason for retrocalcaneal bursitis. It is possible of late
      detection of benign osteochondromas which show symptomatic growth and pressure
      effect in skeletally mature patients without malignant transformation.

PMID- 27703932
TI  - Acromioclavicular Joint Dislocation with Ipsilateral Mid Third Clavicle, Mid
      Shaft Humerus and Coracoid Process Fracture - A Case Report.
AB  - INTRODUCTION: The clavicle, humerus and acromioclavicular (AC) joint separately
      are very commonly involved in traumatic injuries around the shoulder.
      Acromioclavicular joint dislocation with distal clavicle fracture is a well
      recognized entity in clinical practice. AC joint dislocation with mid shaft
      clavicle fracture is uncommon and only few cases have been reported in
      literature. However, to the best of our knowledge, this is the first case report
      to describe an acromioclavicular dislocation with ipsilateral mid shaft clavicle,
      mid shaft humerus and coracoid process fracture. Fractures of the humerus and
      clavicle along with the acromioclavicular joint dislocation were fixed at the
      same setting. CASE REPORT: A 65-year-old male met with a high velocity road
      traffic accident. Plain radiographs showed displaced mid third clavicle fracture
      with acromioclavicular joint dislocation with mid shaft humerus fracture.
      Surgical fixation was planned for humerus with interlocking nail, clavicle with
      locking plate and acromioclavicular joint with reconstruction of coracoclavicular
      ligaments. Intraoperatively, coracoid process was found to have a comminuted
      fracture. The operative plan had to be changed on table as coracoclavicular
      fixation was not possible. So acromioclavicular joint fixation was done using
      tension band wiring and the coracoclavicular ligament was repaired using a 2-0
      ethibond. The comminuted coracoid fracture was managed conservatively. K wires
      were removed at 6 weeks. Early mobilization was started. CONCLUSION: In
      acromioclavicular joint injuries, clavicle must be evaluated for any injury.
      Although it is more commonly associated with distal clavicle fractures, it can be
      associated with middle third clavicle fractures. As plain radiographs, AP view
      are most of the times insufficient for viewing integrity of coracoid process,
      either special views like Stryker notch or CT scan may help in diagnosing such
      concealed injuries. When associated with fractures of the humerus and clavicle,
      anatomical restoration of acromioclavicular joint along with anatomical reduction
      and a rigid fixation of associated fractures is essential. Proper rehabilitation
      protocol is a must for achieving promising results. In our case, we were able to
      achieve a stable surgical fixation of both the fractures as well as AC joint,
      which enabled us to start early joint mobilization and rehabilitation.

PMID- 27703933
TI  - Coexistence of Extraskeletal Mesenchymal Chondrosarcoma and Isolated
      Hemihyperplasia: A Case Report.
AB  - INTRODUCTION: Arthroscopic fixation of tibial spine fracture without damage to
      the growth plate is very important in patients with open physis. The present
      article describes a simple and effective technique being used for the first time
      to treat this condition. CASE REPORT: A 16-year-old boy sustained avulsion
      fractures of tibial spine while playing. He was treated arthroscopically with
      excellent result. CONCLUSION: Arthroscopic fixation of tibial spine fracture in
      patients with open physis with two cannulated screws perpendicular to each other
      is a very simple technique which provides strong construct, and allows early
      mobilization without risk of damage to the growth plate.

PMID- 27703934
TI  - A Case of Septic Arthritis of Shoulder Presenting as Stiffness of the Shoulder.
AB  - INTRODUCTION: Septic arthritis of the shoulder is uncommon in adults. It is a
      surgical emergency as joint destruction occurs rapidly and can lead to
      significant morbidity and mortality. Accurate diagnosis can be particularly
      challenging in patients with underlying liver disease. MRI is a useful adjunct in
      early detection of atypical causes of shoulder pain. CASE REPORT: A 43 years old
      male came to our outpatient department with complaints of pain and stiffness of
      his left shoulder. On examination, his shoulder movements were severely
      restricted. Further evaluation with MRI revealed septic arthritis of left gleno
      humeral joint for which emergency arthroscopic debridement was done. CONCLUSION:
      Septic arthritis of shoulder may not present with classical clinical features.
      Hence, a through clinical and radiological evaluation will help us prognosticate
      and treat accordingly thereby preventing complications like septic shock,
      osteomyelitis.

PMID- 27703935
TI  - Major Surgery in A Jehovah Witness with Sickle Cell Disease: Case Presentation.
AB  - INTRODUCTION: A Jehovah's Witness belongs to the religious group that does not
      accept blood transfusion in any form, while a sickle cell disease patient has
      abnormal haemoglobins that do not last in circulation predisposing one to anaemia
      and other systemic complications. Performing a major surgery in a Jehovah's
      Witness who has sickle cell disease is tasking for a surgeon. CASE PRESENTATION:
      This case reports a 28-year-old African female with sickle cell disease who
      outrightly refused any form of blood transfusion as being a Jehovah's Witness and
      having a complex primary hip that required total hip replacement. This work
      highlighted the complexity and difficulty encountered by virtue of the fact that
      patient had orthopaedic complications of Sickle Cell Disease and measures taken
      to prevent sickling crisis. CONCLUSION: It is possible to carry out major surgery
      in a sickler who has durable power of attorney not to receive blood, but optimum
      preparation, meticulous and fast surgery and adequate monitoring must be
      instituted to avert morbidity and mortality seen in this group of patients.

PMID- 27703936
TI  - Short stature Revealing a Pycnodysostosis: A Case Report.
AB  - INTRODUCTION: Pycnodysostosis is a rare genetic disease characterized by
      osteosclerosis and bone fragility. The clinical aspects are varied including
      short stature, acro-osteolysis of distal phalanges, and dysplasia of the
      clavicles. Oral and maxillofacial manifestations of this disease are very clear.
      The head is usually large, a beaked nose, obtuse mandibular angle, and both
      maxilla and mandible are hypoplastic. Dental abnormalities are common. We report
      a case with the typical clinical and radiological characteristics of the
      Pycnodysostosis associated with a conductive hearing loss, an association rarely
      reported. CASE PRESENTATION: A 12-year-female was admitted in our institute for
      short stature with a dysmorphic facies for evaluation. The patient reported a
      history of multiple fractures of the long bones after a trivial fall. On physical
      examination, she had the following features: short stature, limited mouth
      opening, short hands and feet with dysplastic nails; frontal and occipital
      bossing; and hypoplasia of the maxilla and mandible. Examination of the mouth:
      grooved palate, caries of the teeth, impacted and malposed teeth, persistent
      deciduous teeth and missing teeth. Laboratory investigations were normal. The
      radiographic examination showed a generalized increase in the bone density,
      slight condensation of the skull base and a very open mandibular angle. X-rays
      showed tapered phalanges with acro-osteolysis of the distal phalanges. A
      symptomatic treatment was proposed based on fracture prevention, oral hygiene,
      frequent dental visits and psychiatric support. CONCLUSION: The clinical and
      radiological features are the bases for the diagnosis of this disease. It is
      important to make the diagnosis as early as possible in order to plan the
      treatment and to provide a better life quality to the patients.

PMID- 27703937
TI  - Mega Prosthetic Replacement of Elbow for Resistant Nonunion of Distal Humerus.
AB  - INTRODUCTION: Fractures of the distal humerus are a rare entity accounting for
      approximately 2% of the humeral fractures. Non union of the distal humerus is
      further rare and poses a major challenge. These fractures usually respond to open
      reduction and bone grafting but some may fail multiple surgical attempts at union
      and hence are labelled as "resistant" non union. We report a case of resistant
      non union of the distal humerus which was managed by total elbow arthroplasty.
      CASE PRESENTATION: A 49-year-old male presented to the out patient department
      with history of a compound comminuted fracture of the distal end of the humerus
      approximately 25 years back. The fracture was treated with multiple debridements
      and plaster cast application. There was involvement of the radial and the ulnar
      nerves as well. The patient continued to use the disabled upper limb with severe
      difficulties in activities of daily living (ADL). The patient finally presented
      to us for regaining some range of motion and improvement in his ADL. In view of
      the grossly distorted anatomy, bone loss and chronic nature of the problem,
      patient was offered total elbow arthroplasty. The Wadsworth extensile posterior
      approach was used for exposure of the non union site. The fragments were found to
      be small, osteoporotic and deformed. In view of the distorted anatomy, the elbow
      was finally salvaged with mega-prosthetic replacement of the elbow. Posterior
      elbow splint was used for 2 weeks and active as well as passive range of motion
      was started after that. The post-operative Mayo elbow score improved from 50 to
      80 and the patient was able to achieve a range of motion from 10 degrees to 110
      degrees. CONCLUSION: Total elbow arthroplasty can be used as a salvage procedure
      for resistant non union of the elbow with failed multiple failed attempts at
      union. It can also be used as a definitive procedure for severely distorted non
      union with massive bone loss with satisfactory functional results.

PMID- 27703938
TI  - Novel Presentation of Uncommon Wrist Injury: Simultaneous Lunate and Perilunate
      Fracture Dislocation (scapho-capitate Syndrome) of Both Wrists.
AB  - INTRODUCTION: Perilunate and lunate dislocations are uncommon high energy
      injuries and have extensive soft tissue, cartilaginous and bony damage. The most
      common pattern is trans-scaphoid perilunate fracture dislocation which
      constitutes approximately 50% of these injuries. Unusual injury pattern like
      Scaphocapitate syndrome can occur with fracture through scaphoid waist and
      capitate that rotates the proximal capitate 180 degrees  so that its proximal
      articular surface points distally. With this case report, we would like to
      present a novel presentation of an uncommon wrist injury. CASE REPORT: We present
      a case of simultaneous lunate dislocation in one wrist and perilunate fracture
      dislocation (Scapho- capitate syndrome) in the contralateral wrist which occurred
      simultaneously in a young male following a two wheeler accident. The injury was
      missed initially at the primary treating centre. Upon diagnosis, the patient
      underwent open reduction and internal fixation along with ligament repair. The
      patient was subsequently followed up for a period of four years and was found to
      have very good clinical and radiological outcome. CONCLUSION: These injuries
      occurring simultaneously in contralateral wrists are exceptionally rare and
      unusual as the mechanisms of injury are different. These are high velocity
      injuries and are often missed, especially in presence of other major injuries.
      These high energy injuries need accurate diagnosis, early and aggressive
      treatment in order to prevent complications.

PMID- 27703939
TI  - BBilateral Neglected Anterior Shoulder Dislocation with Greater Tuberosity
      Fractures.
AB  - INTRODUCTION: Shoulder dislocations are a very common entity in routine
      orthopaedic practice. Chronic unreduced anterior dislocations of the shoulder are
      not very common. Neurological and vascular complications may occur as a result of
      an acute anterior dislocation of the shoulder or after a while in chronic
      unreduced shoulder dislocation. Open reduction is indicated for most chronic
      shoulder dislocations. We report a case of neglected bilateral anterior shoulder
      dislocation with bilateral displaced greater tuberosity fracture. To the best of
      our knowledge, only a handful cases have been reported in literature with
      bilateral anterior shoulder dislocation with bilateral fractures. Delayed
      diagnosis/reporting is a scenario which makes the list even slimmer and
      management all the more challenging. CASE REPORT: We report a case of a 35-year
      old male who had bilateral anterior shoulder dislocation and bilateral greater
      tuberosity fracture post seizure and failed to report it for a period of 30 days.
      One side was managed conservatively with closed reduction and immobilization and
      the other side with open reduction. No neurovascular complications pre or post
      reduction of shoulder were seen. CONCLUSION: Shoulder dislocations should always
      be suspected post seizures and if found should be treated promptly. Treatment
      becomes difficult for any shoulder dislocation that goes untreated for
      considerable period of time.

PMID- 27703940
TI  - Salvage of a Below Knee Amputation Utilizing Rotationplasty Principles in a
      Patient with Chronic Tibial Osteomyelitis.
AB  - INTRODUCTION: Chronic osteomyelitis is a disease that requires fastidious
      treatment to eliminate. However, when eradication is unable to be achieved
      through exhaustive modalities of antibiotic therapy and multiple debridements,
      significant resection of the infected bone and soft tissue must be considered,
      including amputation. Here we report of a salvage procedure for chronic
      osteomyelitis of the left tibia by employing a rotationplasty to avoid an above
      knee amputation and instead provide the patient with a below knee amputation.
      CASE REPORT: A 51-year-old male presented to the emergency department after
      noticing dehiscence of an operative wound with exposure of an implant in the left
      lower extremity. Two years prior to presentation, the patient was involved in a
      motorcycle accident and underwent four surgeries in the Dominican Republic for an
      open fracture of the left tibia and fibula, including a procedure that involved
      the placement of an implant in the left proximal tibia. Tissue biopsies from the
      wound confirmed that the patient had osteomyelitis of the left proximal tibia.
      After extensive surgical and antibiotic intervention to eradicate the patient's
      osteomyeltis, it was eventually determined that an amputation would be necessary.
      In order to avoid an above knee amputation, a salvage procedure was conducted by
      employing a rotationplasty to provide the patient with a below knee amputation.
      CONCLUSION: When amputation is deemed necessary, sparing the knee joint is
      associated with decreased energy expenditures, increased patient satisfaction and
      overall better postoperative outcomes. As part of a multi-disciplinary team,
      orthopaedics, plastic surgery, infectious disease, and medical services
      successfully treated this case of chronic osteomyelitis of the left proximal
      tibia by employing a rotationplasty to avoid an above knee amputation and achieve
      a below knee amputation.

PMID- 27703941
TI  - Schwannoma of the Median Nerve at Mid Forearm Level.
AB  - INTRODUCTION: Schwannomas are also known as neurilemmoma that usually originate
      from Schwann cells located in the peripheral nerve sheaths. It usually occurs in
      the age group of 20 to 70 years. These are the commonest tumors of the peripheral
      nerves, 5% of which occur in the adults and 19% of the tumors occur in upper
      extremities. Schwannomas are generally presented as an asymptomatic mass.
      Discomfort may be the only presenting complaint of the patient. Paresthesia may
      be elicited on tapping the swelling. Magnetic resonanceimaging, and ultrasound
      are helpful in the diagnosis. Surgical removal is usually curative. CASE
      PRESENTATION: A 28-year-old male came to our hospital for a lump located at the
      volar side of the right mid forearm for 10 years with discomfort and paresthesia
      in median nerve distribution of hand which appeared in last two years. Total
      excision was performed for the lesion. Histopathological examination of the mass
      revealed typical features of schwannoma. At two months follow-up, the patient was
      symptom free with mild paresthesia in his index and middle fingers. CONCLUSION:
      Benign tumours involving peripheral nerves of the upper extremity are uncommon.
      Schwannomas are theoretically removable because they repulse fascicular groups
      without penetrating them, thus allowing their enucleation while preserving nerve
      continuity, as reported in our patient.

PMID- 27703942
TI  - Bilateral Spontaneous Midsubstance Patellar Tendon Rupture after Bilateral Total
      Knee Arthroplasty.
AB  - INTRODUCTION: Patellar tendon rupture can occur due to multiple causes ranging
      from inflammatory pathologies to episodes of trauma. Extensor mechanism rupture
      is a rare complication of total knee arthroplasty (TKA). In most of these cases,
      the failure occurs as avulsion of patellar tendon from tibial tuberosity. We
      report a rare case with bilateral mid-substance patellar tendon rupture one month
      after bilateral total knee arthroplasty. CASE PRESENTATION: A 69-year-old male
      was operated for bilateral grade 4 osteoarthritis. On day 30 post-operative, he
      sustained bilateral patellar tendon rupture while getting up from toilet. He had
      a history of multiple steroid injections in the knee, which could have affected
      the tendon. The other etiologies could be inherent weakness of tendon due to
      diabetes and old age and micro-trauma/stretch associated with sudden correction
      of previous deformity by TKA. The management in our case was done by primary
      repair along with augmentation by autologous semitendinosus graft and suture
      anchor. CONCLUSION: The operating surgeon must be aware of the possibility of
      patellar tendon rupture following total knee arthroplasty. This will help the
      surgeon in early recognition and preparedness to handle such complications,
      should they arise. Surgeons may consider advising caution to both patient and
      rehabilitation team in cases with old age, chronic diabetes mellitus, and with a
      history of steroid injections.

PMID- 27703943
TI  - Slipped Distal Femoral Epiphysis in Congenital Insensitivity to Pain.
AB  - INTRODUCTION: Congenital insensitivity to pain (CIP) is a rare disorder, and
      often presents to an orthopaedic surgeon as recurrent fractures, dislocations,
      pseudoarthrosis, osteomyelitis etc. Here, we report a case of congenital
      insensitivity to pain presenting with distal femoral physeal separation in a
      child. CASE REPORT: A 12-year-old girl child came with complaints of limp while
      walking and swelling in the left knee for past 5 weeks. Mother gave a history
      that the girl is a known case of congenital insensitivity to pain with clear
      history of no pain on intramuscular injection since birth. She was born of
      consanguineous marriage and had no significant trauma, fever, other joint
      involvement or any features of rheumatism. On local examination, she had no bony
      tenderness, mild warmth, and moderate knee effusion with restricted range of
      movement. Plain radiograph showed epiphysiolysis of distal femur with widening of
      physis. Examination under anaesthesia demonstrated gross movement indicating
      lower femoral physeal separation. This unstable distal femoral epiphysis was
      treated under general anaesthesia with closed reduction, percutaneous cross
      pinning and above knee plaster cast. CONCLUSION: Congenital insensitivity to pain
      (CIP) is a rare disorder to diagnose. Emphasis is given on early diagnosis of
      orthopaedic problems and prompt treatment, educating parents and prevention of
      accidents. Physeal separation without significant trauma must prompt an
      orthopaedic surgeon to think about congenital insensitivity to pain as a
      differential diagnosis.

PMID- 27703944
TI  - Intraosseous Leiomyoma of the Tibia. A Case Report.
AB  - INTRODUCTION: Leiomyoma is benign smooth-muscle tumor most commonly arising in
      the uterus, the gastrointestinal tract, and the skin. Leiomyomata are
      infrequently seen in the extremities and rarely seen in the bone. It is usually
      presented by a gradually increasing pain with nonspecific radiological findings,
      and could be a differential diagnosis for wide range of bone tumors. CASE
      PRESENTATION: We report a case of a 73-year-old Japanese female patient with a
      painful intraosseous leiomyoma involving the proximal tibia. The patient had
      undergone tumor excision with wide margin, immediate weight bearing was allowed,
      pain had been relieved and the patient was satisfied with no recurrence,
      malignant change, distant metastases or functional impairment. We reviewed all
      published cases of intraosseous leiomyomata in English literature. CONCLUSION:
      Diagnosis of Intraosseous leiomyoma of the extremities is difficult due to
      extreme rarity of the tumor and absence of pathognomonic radiological sign in X
      ray, CAT, or even MRI. While the exact diagnosis is only achieved by
      histopathological examination and with immunohistochemistry stains, which can
      differentiate it from malignancy, especially from the much less rare
      leiomyosarcoma. Orthopedic oncologists have to include this rare benign tumor in
      the differential diagnosis of any intraosseous lesion with gradually worsening
      and long-standing pain, despite of benign imaging characters. Different
      histological patterns of leiomyoma do exist, however there is no difference in
      prognosis or treatment options. Treatment standard includes wide excision with
      autologous bone graft whenever possible. Internal fixation may be necessary if
      the bone defect is large or there is thinning out of the cortex that may lead to
      pathological fracture.

PMID- 27703945
TI  - Arthroscopic Fixation of Tibial Spine Avulsion Fracture in Open Physis.
AB  - INTRODUCTION: Arthroscopic fixation of tibial spine fracture in patients with
      open physis without damaging the growth plate is very important. We have
      described a very simple and effective technique for the first time in this
      article. CASE REPORT: A 16-year-old boy sustained avulsion fractures of tibial
      spine while playing. He was treated arthroscopically with excellent results.
      CONCLUSION: Arthroscopic fixation of tibial spine fracture in patients with open
      physis with two cannulated screws perpendicular to each other is a very simple
      technique providing strong construct, and allowing early mobilization without
      risk of damage to the growth plate.

PMID- 27703946
TI  - Open Periprosthetic Patellar Fracture after Total Knee Replacement.
AB  - INTRODUCTION: Periprosthetic patellar fracture after total knee arthroplasty
      (TKA) is a rare complication. Their management can be very challenging with
      unpredictable results. Literature analysis showed few articles about this
      complication, but no publication has described the management of open patella
      fracture around total knee arthroplasty. CASE PRESENTATION: We report a unique
      case of an open patellar fracture above a total knee arthroplasty, sustained by a
      56-year-old female patient. CONCLUSION: Despite the poor outcome of operative
      management in patellar periprosthetic fracture, this approach should be
      considered for acute and post traumatic fractures in young patients with a good
      remaining bone stock.

PMID- 27703947
TI  - Erythromycin Seromadesis in Orthopedic Surgery.
AB  - INTRODUCTION: The presence of postoperative seromadesis is common, corresponding
      to the presence of serum in the subcutaneous tissue post a surgical event.
      Erythromycin has been reported as sclerosing, although not in orthopedic surgery.
      We report a case of erythromycin seromadesis in orthopedic surgery. CASE
      PRESENTATION: We present a case of a 63-year-old woman having undergone femoral
      prosthesis surgery and total hip replacement with a subfacial seroma without
      findings of infection, refractory to standard treatment of compression bandages,
      massage and cleaning surgery in two oportunities. A literature review was
      undertaken to obtain the therapeutic alternatives where erythromycin seromadesis
      is chosen with excellent response. CONCLUSION: Erythromycin sclerotherapy should
      be considered as an effective and safe option in the treatment of seroma in
      general surgery and traumatology. More studies are necessary to get a better
      evidence. We believe that this is the first study of use of erythromycin as
      sclerotherapy in a traumatology case.

PMID- 27703948
TI  - Recurrent Patellar Instabilty Culminating in a Vertically Rotated and a Locked
      Patellar Dislocation - A Rare Entity.
AB  - INTRODUCTION: Locked vertical patellar dislocations are rare and pose a
      therapeutic challenge. This case is more unusual, as the patient was a known case
      of recurrent patellar dislocation and presented with an atraumatic locked and
      vertically rotated patellar dislocation. This type of presentation has never been
      reported in literature to the best of our knowledge. CASE PRESENTATION: A 14-year
      old healthy male child with previous history of recurrent lateral dislocation of
      patella presented to accident & emergency department with complaints of inability
      to walk or bear weight on his left lower limb after he spontaneously dislocated
      his patella while running on uneven ground. Radiographs revealed a laterally
      displaced and vertically rotated patella along its long axis with the medial
      patellar edge locked and dipping into the lateral gutter. Open reduction was
      performed along with lateral patellar retinacular release with medial patellar
      retinaculum plication, to achieve satisfactory patellar stability and
      patellofemoral tracking. CONCLUSION: We would recommend that in the settings of
      patella being vertically dislocated and locked, open reduction would be the
      management of choice, as these types of dislocations are difficult to relocate by
      closed reduction. Repeated attempts of closed reduction may cause osteochondral
      damage. Open reduction not only yields better outcomes but also allows the
      surgeon to perform patellar realignment procedures in order to prevent further
      patellar dislocations in cases of prior patellar instability.

PMID- 27703949
TI  - A Case Report of Curettage and Kryptonite(r) use in Proximal Femur Intraosseous
      Lipoma.
AB  - INTRODUCTION: Intraosseous lipomas are the most infrequent primary bone tumor,
      lesions are mainly asymptomatic and generally diagnosed incidentally, and there
      is controversy about the management. Here, we present a surgery solution that has
      not been described previously in literature. CASE PRESENTATION: A 23-year-old
      female without previous morbid history consults a general physician because of
      unspecific left hip pain when walking, not related to any previous trauma or any
      other symptoms. In her study, radiography of the sore hip showed a radiopaque
      lesion with lithic aspect at the neck of the left femur. CONCLUSION: Intraosseous
      lipoma, in spite of being a rare condition, can be diagnosed incidentally by its
      radiologic characteristics. The treatment can be based on observation or surgery
      in particular cases objectified by clinic and Mirel score.

PMID- 27703951
TI  - ?

PMID- 27703950
TI  - Acute Cholecystitis Following Total Knee Replacement: A Case Report and
      Literature Review.
AB  - INTRODUCTION: Infection poses a substantial challenge after joint replacement.
      CASE PRESENTATION: We report a 53-year-old female with multiple co-morbidities,
      who underwent unilateral total knee arthroplasty. Her postoperative course was
      complicated by acute cholecystitis necessitating cholecystectomy. CONCLUSION: In
      patients who require joint replacement surgery, careful and detailed preoperative
      assessment is important to identify those at risk for this complication in order
      to provide timely treatment.

PMID- 27703952
TI  - The Value of Urodynamic Study for Diagnosing the Causes of Lower Urinary Tract
      Symptoms in Male Patients: A Study From Iran.
AB  - BACKGROUND: Most disorders of the lower urinary tract are functional, so
      diagnoses are typically based on urodynamic findings. Treatment is likely to fail
      if the pathology is not correctly diagnosed. OBJECTIVES: There are various
      diagnostic tests for lower urinary tract symptoms (LUTS). In this study, we
      evaluated the value of urodynamic testing to diagnose the causes of lower urinary
      symptoms in male patients. PATIENTS AND METHODS: Urodynamic tests were performed
      in 407 patients referred to the urology clinic in Baqiyatallah in 2014 with
      complaints of LUTS, and the diagnosis was based on the findings of the tests.
      RESULTS: The mean age of patients in this study was 50.88 years, and most
      patients were in their third decade (20 - 30 years of age). Urinary frequency
      (28.8%), enuresis (22.22%), and incontinence (16.12%) were the most common
      complaints. The most prevalent disorder was bladder sensation disorder.
      CONCLUSIONS: Patients made various complaints, and several pathologies were
      diagnosed, which emphasizes the importance of using urodynamic tests for
      subsequent medical approaches as a non-invasive, accessible, and inexpensive
      tool.

PMID- 27703953
TI  - Primary Nocturnal Enuresis: A Review.
AB  - CONTEXT: Nocturnal enuresis or bedwetting is the most common type of urinary
      incontinence in children. It has significant psychological effects on both the
      child and the family. Enuresis nocturna is defined as the inability to hold urine
      during the night in children who have completed toilet training. It is termed as
      being "primary" if no continence has ever been achieved or "secondary if it
      follows at least 6 months of dry nights. The aim of this review was to assemble
      the pathophysiological background and general information about nocturnal
      enuresis. EVIDENCE ACQUISITION: This review was performed by evaluating the
      literature on nocturnal enuresis published between 1970 and 2015, available via
      PubMed and using the keywords "nocturnal enuresis," "incontinence," "pediatric,"
      "review," and "treatment." RESULTS: Children with nocturnal enuresis produce
      urine at higher rates during the night, and may have lower bladder capacities.
      Some children with nocturnal enuresis may also have daytime urgency, frequency,
      and urinary incontinence. Treatment includes aggressive treatment of accompanying
      constipation or urinary tract infections, behavioral changes, and medical
      therapy. Alarm therapy remains the first-line treatment modality for primary
      nocturnal enuresis. High rates of patient compliance and relapse mean that
      alternative treatments remain on the agenda. CONCLUSIONS: Nocturnal enuresis is a
      common problem that has multifaceted effects on both the child and the family.
      Due to multiple etiologic factors, nocturnal enuresis is still not clearly
      defined.

PMID- 27703954
TI  - Multimodal Analgesia With Ketamine or Tramadol in Combination With Intravenous
      Paracetamol After Renal Surgery.
AB  - BACKGROUND: Opioids are generally the preferred analgesic agents during the early
      postoperative period. OBJECTIVES: The present study was designed to assess and
      compare the multimodal analgesic effects of ketamine and tramadol in combination
      with intravenous acetaminophen after renal surgery. PATIENTS AND METHODS: This
      randomized, double-blinded, clinical trial was conducted on 80 consecutive
      patients undergoing various types of kidney surgeries in Sina hospital in Tehran
      in 2014 - 2016. After extubation, the patients were randomly assigned to receive
      intravenous paracetamol (1 gr) plus tramadol (0.7 mg/kg) (PT group) or
      paracetamol (1 gr) plus ketamine (0.5 mg/kg) (PK group) within ten minutes. Pain
      severity was assessed by the visual analog scale (VAS), and the level of
      agitation was assessed by the Ramsey sedation scale (RSS). Morphine consumption
      was assessed within the first six hours after drug injection, and hemodynamic
      parameters were assessed at 5, 10, and 20 minutes after infusion, at the time of
      transfer from recovery to the ward, and also at one and six hours after transfer
      to the ward. RESULTS: Postoperative pain scores were significantly lower in the
      PK group than in the PT group during all study time points. The mean dose of
      morphine needed at recovery in the PK group was lower compared with the PT group
      (0.47 +/- 0.94 mg versus 1.50 +/- 1.35 mg/P = 0.001). The level of agitation
      based on the RSS score was significantly lower in the PK group than in the PT
      group at 10 and 20 minutes after drug administration. The total postoperative
      complication rate in the PK group was lower than in the PT group (20% versus
      53.3%, P = 0.007). In this regard, catheter bladder discomfort was more frequent
      in the PT group than in the PK group (43.3% versus 3.3%, P < 0.001). CONCLUSIONS:
      The combination of intravenous paracetamol 1 gr and ketamine 0.5 mg/kg resulted
      in an overall reduction in pain scores, decreased postoperative analgesic
      requirements, and lower agitation score compared with intravenous paracetamol 1
      gr and tramadol 0.7 mg/kg for patients undergoing renal surgery.

PMID- 27703955
TI  - A Novel Technique for Post-Prostatectomy Catheter Traction.
AB  - BACKGROUND: Prostate traction is one way to control post-prostatectomy bleeding.
      The most popular method involves traction with a catheter fixed to the thigh with
      adhesive bands. However, this method has its own drawbacks. OBJECTIVES: We aimed
      to simplify this traction procedure and to overcome its disadvantages. PATIENTS
      AND METHODS: From 2007 - 2015, a new method was used to control post
      prostatectomy bleeding in 152 patients. This technique involved inducing pressure
      on the prostate neck with an indwelling catheter attached to a partially filled
      urine bag to control bleeding after a prostatectomy. RESULTS: The new method
      effectively controlled post-prostatectomy bleeding. A few patients required
      surgical intervention. CONCLUSIONS: Post-prostatectomy catheter traction using a
      semi-filled urine bag was an acceptable alternative to the standard method to
      control post-operative bleeding.

PMID- 27703956
TI  - Burden of Hypertension and Abnormal Glomerular Permeability in Hypertensive
      School Children.
AB  - BACKGROUND: Childhood hypertension has been associated with target-organ damage
      in young adults. It is often asymptomatic in both children and adolescents; when
      persistent, and long-standing, it could be a significant risk factor for kidney
      damage and increased glomerular permeability. OBJECTIVES: Burden of hypertension
      and its impact on glomerular permeability were prospectively determined in
      randomly recruited primary school children. PATIENTS AND METHODS: Blood pressure
      (BP) measurement was performed by the auscultation method, and abnormal
      glomerular permeability was assessed by dipstick testing of urine for persistent
      proteinuria and/or hematuria for >= three months in hypertensive children.
      RESULTS: Of 1,335 pupils aged 10.0 +/- 2.4 (6.0 - 14.0) years, 33 (2.5%) were
      hypertensive. Overall mean systolic/diastolic BP was 125.6 +/- 6.5/81.7 +/- 3.3
      (range: 114.0 - 140.0/80.0 - 90.0) mmHg. Nine (27.3%) had combined systolic and
      diastolic hypertension, 126.7 +/- 5.7/80.0 - 80.0 +/- 0.0 (120.0 - 130.0/80.0 -
      80.0) mmHg. Isolated systolic hypertension, 125.4 +/- 6.7 (114.0 - 140.0) mmHg,
      was present in 14 (42.4%), whereas 10 (30.3%) had isolated diastolic
      hypertension, 82.0 +/- 3.5 (80.0 - 90.0) mmHg. Mean systolic and diastolic BP
      were 131.0 +/- 3.3 (130.0 - 140.0) mmHg and 86.5 +/- 4.43 (80.0 - 90.0) mmHg,
      respectively. According to the dipstick test, none of the hypertensive pupils
      showed urinalysis evidence of proteinuria and/or hematuria after three months of
      testing. CONCLUSIONS: Although the burden of hypertension was 2.5%, the dipstick
      method did not detect any hypertension-related abnormal glomerular permeability
      in the school children.

PMID- 27703957
TI  - Primary Renal Primitive Neuroectodermal Tumor/Ewing's Sarcoma Imaging and
      Pathologic Findings of a Patient with a Nine Year, Eight Month Disease Free
      Period: Case Report and Review of Literature.
AB  - INTRODUCTION: Primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (EWS)
      belongs to a family of neoplasms that are presumed to originate from the
      neuroectodermal crest. PNET/EWSs are highly aggressive malignancies that usually
      present in the form of bone or soft tissue masses and usually affect adolescents
      and young adults. Primary PNET/EWS of the kidney is very rare. CASE PRESENTATION:
      We present the case of a 32-year-old female patient with primary renal PNET/EWS
      diagnosed nine years and eight months earlier. The patient presented with acute
      flank pain in the left lumbar region, hematuria, and episodes of high body
      temperature of 40 degrees C. Abdominal ultrasound (US) and subsequently performed
      computed tomography (CT) revealed a large renal mass of heterogenous structure.
      The kidney tumor had central necrotic hypodense areas and strongly peripherally
      enhanced solid parts on postcontrast CT images. Immunohistochemistry revealed
      positivity for CD99 and neuron-specific enolase (NSE). Tumor cells were negative
      for CD3, CD 20, chromogranin, synaptophysin, vimentin, and neurofilament. Reverse
      transcription polymerase change reaction (RT-PCR) revealed EWS/FL1 translocation
      type 2. The patient underwent nephrectomy and polychemotherapy. The follow-up
      nine years and eight months after the diagnosis showed no evidence of tumor.
      CONCLUSIONS: PNET/EWS should be included in the differential diagnosis of renal
      tumors in symptomatic young adults. Patients with localised PNET/EWS treated with
      a combination of surgery and chemotherapy have an excellent chance of long-term
      survival, as in the case we have presented.

PMID- 27703958
TI  - Temporal Patterns of Road Traffic Injuries in Iran.
AB  - BACKGROUND: Road traffic injuries (RTIs) are the main causes of death and
      disability in Iran. However, very few studies about the temporal variations of
      RTIs have been published to date. OBJECTIVES: This study was conducted to
      investigate the temporal pattern of RTIs in Iran in 2012. MATERIALS AND METHODS:
      All road traffic accidents (RTAs) reported to traffic police during a one-year
      period (March 21, 2012 through March 21, 2013) were investigated after obtaining
      permission from the law enforcement force of the Islamic Republic of Iran.
      Distributions of RTAs were obtained for season, month, week, and hour scales, and
      for long holidays (more than one day) and the day prior to long holidays (DPLH).
      The final analysis was carried out using the Poisson regression model to
      calculate incidence rate ratios for RTIs. All analyses were conducted using STATA
      13.1 and Excel software; statistical significance was set at P < 0.05. RESULTS: A
      total of 452,192 RTAs were examined. The estimated rate of all accidents was 219
      per 10,000 registered vehicles, or 595 per 100,000 people. About 28% of all RTAs,
      and more than one third of fatal RTAs, occurred during the summer months. The
      incidence rate for all traffic accidents on DPLH was 1.20, compared to workdays
      as a reference category, and it was 1.40 for fatal crashes. The rate of fatal
      road traffic accidents in outer cities was 3.2 times higher than in inner ones.
      CONCLUSIONS: Our findings reveal that there are temporal variations in traffic
      accidents, and long holidays significantly influence accident rates. Traffic
      injuries have different patterns on outer/inner city roads, based on weekday and
      holiday status. Thus, these findings could be used to create effective
      initiatives aimed at traffic management.

PMID- 27703959
TI  - A Systematic Review of Iranian Experiences in Seismo-Nephrology.
AB  - CONTEXT: Crush syndrome and its potentially life-threatening complications, such
      as acute kidney injury (AKI), are one of the most important medical problems of
      disaster victims. However, today, many unanswered questions abound about the
      potential risk factors of crush syndrome, predictive factors of AKI, proper
      amount of prophylactic hydration therapy, type of fluid, time of continuing
      fluid, intravenous versus oral hydration, etc. Therefore, this study was designed
      to review the findings on Iranian nephrologist experiences in diagnosis and
      management of traumatic rhabdomyolysis following the last two strong earthquakes
      of Bam (2003) and Manjil-Rudbar (1990). EVIDENCE ACQUISITION: The study was
      conducted according to the MOOSE reporting guideline. A literature review was
      conducted on the nephrologic aspects of earthquakes in Iran. Relevant articles
      were identified through a comprehensive search of online databases until 2014.
      The search was limited to articles studying the Iranian population published in
      English and Persian languages. The validated combination of MeSH terms and key
      words was used. In addition, a manual search was run among the references of all
      articles that met the entrance criteria and previous reviews. Only cohort, case
      control, and cross-sectional studies were enrolled. Two reviewers independently
      reviewed the eligible studies, and another reviewer contributed in case of a
      disagreement. Basic information from each study was evaluated from the aspects of
      purpose and design, year of publication, methodology, main population, and source
      of data. The quality of the included studies was assessed using methods guide for
      effectiveness and comparative effectiveness reviews. Two reviewers independently
      rated each paper as "good", "fair", or "poor". RESULTS: A total of 1256 non
      duplicate articles were identified, but only 35 potentially relevant papers were
      screened. Finally, 21 articles were found eligible and studied in details. In
      addition, one unpublished report was included. In the quality assessment, two
      articles had poor quality, and thus only 20 were finally included in the
      systematic review. No publication bias (coefficient = -2.28; 95% Confidence
      interval: -6.17 - 1.78; P = 0.26) was observed among the included studies.
      CONCLUSIONS: A few eligible articles on seismo-nephrology were found in Iran, and
      a limited number of current articles had poor or fair quality. As expected, the
      chaotic situation after mass disasters and the lack of documentation led to the
      loss of much important data on the diagnosis and management of victims. Lessons
      learned from the current researches can be used as a valuable guide for future
      studies.

PMID- 27703960
TI  - Effect of Mild Traumatic Brain Injury and Demographic Factors on Psychological
      Outcome.
AB  - BACKGROUND: It is well-known that severe brain injury can make people susceptible
      to psychological symptoms. However, mild traumatic brain injury (MTBI) is still
      open for discussion. OBJECTIVES: This study aimed to compare psychological
      symptoms of MTBI patients with those without MTBI considering demographic
      auxiliary variables. PATIENTS AND METHODS: This prospective cohort study was
      conducted on 50 MTBI patients and 50 healthy subjects aged 15 - 65 years.
      Psychological assessment was carried out six months post-injury using a series of
      self-report measures including the brief symptom inventory (BSI) scale. Other
      information of the individuals in the two groups was recorded prospectively. Data
      were analyzed using the chi-square test, t-test, and multiple linear regression
      tests. RESULTS: There was a significant difference between the MTBI patients and
      healthy subjects in all subscales and total score of BSI. Our findings showed
      that obsession-compulsion and anxiety subscales were significantly more common in
      the MTBI patients than in the healthy subjects. Also, multivariate regression
      analysis six months post- injury showed that head trauma and substance abuse can
      have an effect on psychological symptoms. CONCLUSIONS: Mild traumatic brain
      injuries despite of the normal CT scan and history of substance abuse are closely
      related to psychological symptoms. Therefore, it is recommended that patients
      with brain trauma 6 months post-injury and subjects with a history of substance
      abuse be evaluated for psychological distress to support better rehabilitation.

PMID- 27703961
TI  - Hajj Stampede in Mina, 2015: Need for Intervention.

PMID- 27703962
TI  - Role of regorafenib as second-line therapy and landscape of investigational
      treatment options in advanced hepatocellular carcinoma.
AB  - Sorafenib is still the only systemic drug approved for the treatment of advanced
      hepatocellular carcinoma (HCC). In recent years, several investigational agents
      mainly targeting angiogenesis failed in late-phase clinical development due to
      either toxicity or lack of benefit. Recently, data of the RESORCE trial, a
      placebo-controlled Phase III study that evaluated the efficacy and safety of
      regorafenib in patients with HCC and documented disease progression after
      systemic first-line treatment with sorafenib, were presented at the ESMO World
      Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a
      2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side
      effects were consistent with the known profile of regorafenib. The approval of
      regorafenib for this indication is expected in 2017. Further candidate agents in
      Phase III evaluation for second-line treatment of patients with HCC are the MET
      inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor
      receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1)
      blocking antibody pembrolizumab. Furthermore, results from two first-line trials
      with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody
      nivolumabin in comparison to sorafenib are awaited in the near future and might
      further change the treatment sequence of advanced HCC.

PMID- 27703963
TI  - Does alpha-fetoprotein contribute to the mortality and morbidity of human
      hepatocellular carcinoma? A commentary.
AB  - The fifth most common cancer worldwide is hepatocellular carcinoma (HCC), while
      being the third leading cause of global cancer-related deaths. Although HCC
      incidence is less frequent in North America, it is a common malignancy in Asia
      and Africa associated with a high rate of mortality and morbidity due to
      ineffective therapies against cancer growth, invasion, and metastasis. It is well
      established that serum alpha-fetoprotein (AFP) is the "gold standard" biomarker
      for liver cancer; however, less known are the biological activities of AFP
      regarding carcinogenesis, growth, proliferation, and metastasis. Clinicians are
      well aware that increasing AFP serum levels parallel disease progression of HCC
      patients, but many are less knowledgeable in the lethal growth-promoting
      properties of AFP as an autocrine stimulator of hepatoma cell proliferation. This
      commentary addresses the mortality and morbidity concerning AFP in the genesis,
      growth, progression, and spread of HCC and emphasizes the perilous consequences
      of AFP-supported growth in human liver cancer even after liver resection and
      transplantation. Thus, AFP is not just a biomarker for HCC but also an ardent
      promoter of liver cancer growth and progression.

PMID- 27703964
TI  - Job Maintenance through Supported Employment PLUS: A Randomized Controlled Trial.
AB  - Sickness absence from work due to experienced distress and mental health issues
      has continuously increased over the past years in Germany. To investigate how
      this alarming development can be counteracted, we conducted a randomized
      controlled trial evaluating a job coaching intervention to maintain the working
      capacity of members of staff and ultimately prevent sickness absence. Our sample
      included N = 99 employees who reported mental distress due to work-related
      problems. The intervention group (n = 58) received between 8 and 12 individual
      job coaching sessions in which they worked with a professional job coach to
      reduce their mental distress. The control group (n = 41) received a brochure
      about mental distress. Data were collected before the start of the study, at the
      end of the job coaching intervention, and at a 3-month follow-up. These data
      included the number of sickness absence days as the primary outcome and
      questionnaire measures to assess burnout indicators, life satisfaction, and work
      related experiences and behaviors. Compared with the control group, the results
      indicated no reduction in sickness absence in the intervention group but fewer
      depressive symptoms, a heightened ability of the participants to distance
      themselves from work, more experience of work-related success, less depletion of
      emotional resources, and a greater satisfaction with life when participants had
      received the job coaching. Thus, although we could not detect a reduction in
      sickness absence between the groups, job coaching was shown to be a viable
      intervention technique to benefit employees by contributing to re-establish their
      mental health. We discuss the implications of the study and outline future
      research.

PMID- 27703965
TI  - Occupational Practitioner's Role in the Management of a Crisis: Lessons Learned
      from the Paris November 2015 Terrorist Attack.
AB  - In massive catastrophic events, occupational health practitioners are more and
      more frequently involved in the management of such situations. We aim to describe
      the multiple aspects of the role that occupational health practitioners might
      play, by focusing on the recent example of the Paris terrorist attack of November
      2015. During and after the Paris attack, occupational practitioners, in
      collaboration with emergency and security professionals, were involved in
      psychological care, assembling information, follow-up, return-to-work, and
      improving in-company safety plans. Based on this experience and other industrial
      disasters, we distinguish three phases: the critical phase, the post-critical
      phase, and the anticipation phase. In the critical phase, the occupational
      practitioner cares for patients before the emergency professionals take charge,
      initiates the psychological management, and may also play an organizational role
      for company health aspects. In the post-critical phase, he or she would be
      involved in monitoring those affected by the events and participate in
      preventing, to the extent possible, posttraumatic stress disorder, helping
      victims in the return-to-work process, and improving procedures and organizing
      drills. In addition to their usual work of primary prevention, occupational
      practitioners should endeavor to improve preparedness in the anticipation phase,
      by taking part in contingency planning, training in first aid, and defining
      immediately applicable protocols. In conclusion, recent events have highlighted
      the essential role of occupational health services in anticipation of a crisis,
      management during the crisis, and follow-up.

PMID- 27703966
TI  - Marked QTc Prolongation and Torsades de pointes in Patients with Chronic
      Inflammatory Arthritis.
AB  - Mounting evidence indicates that in chronic inflammatory arthritis (CIA), QTc
      prolongation is frequent and correlates with systemic inflammatory activation.
      Notably, basic studies demonstrated that inflammatory cytokines induce profound
      changes in potassium and calcium channels resulting in a prolonging effect on
      cardiomyocyte action potential duration, thus on the QT interval on the
      electrocardiogram. Moreover, it has been demonstrated that in rheumatoid
      arthritis (RA) patients, the risk of sudden cardiac death is significantly
      increased when compared to non-RA subjects. Conversely, to date no data are
      available about torsades de pointes (TdP) prevalence in CIA, and the few cases
      reported considered CIA only an incidental concomitant disease, not contributing
      factor to TdP development. We report three patients with active CIA developing
      marked QTc prolongation, in two cases complicated with TdP degenerating to
      cardiac arrest. In these patients, a blood sample was obtained within 24 h from
      TdP/marked QTc prolongation occurrence, and levels of IL-6, TNFalpha, and IL-1
      were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times
      more than reference values. Moreover, one patient also showed high circulating
      levels of TNFalpha and IL-1. In conclusion, active CIA may represent a currently
      overlooked QT-prolonging risk factor, potentially contributing in the presence of
      other "classical" risk factors to TdP occurrence. In particular, a relevant role
      may be played by elevated circulating IL-6 levels via direct electrophysiological
      effects on the heart. This fact should be carefully kept in mind, particularly
      when recognizable risk factors are already present and/or the addition of QT
      prolonging drugs is required.

PMID- 27703967
TI  - Persistent Type I Endoleak after Endovascular Treatment with Chimney Technique.
AB  - Thoracic endovascular aortic repair (TEVAR) is increasingly used in the treatment
      of acute type B aortic dissection. Type Ia endoleaks are a common complication of
      the procedure, but its clinical significance and the best treatment strategy
      remain poorly defined. We present a case of a type Ia endoleak following TEVAR in
      the treatment of acute type B aortic dissection. Chimney technique approach was
      used in an attempt to seal the endoleak. Although technical success was
      suboptimal, the patient remained clinically stable and event free. Data regarding
      the natural course and management of type Ia endoleaks following TEVAR for aortic
      dissection are sparse. Future research is required to establish the clinical and
      technical determinants of the need to treat these endoleaks and the best
      treatment strategy.

PMID- 27703968
TI  - G-1639A but Not C1173T VKORC1 Gene Polymorphism Is Related to Ischemic Stroke and
      Its Various Risk Factors in Ukrainian Population.
AB  - Vitamin K epoxide reductase complex subunit 1 (VKORC1) is integral 163-amino acid
      long transmembrane protein which mediates recycling of vitamin K 2,3-epoxide to
      vitamin K hydroquinone and it is necessary for activation of vitamin K-dependent
      proteins (VKDPs). Herein, the association between G-1639A (rs9923231) and C1173T
      (rs9934438) single-nucleotide polymorphisms (SNPs) of the VKORC1 gene and
      ischemic stroke (IS) was tested in Ukrainian population. Genotyping was performed
      in 170 IS patients and 124 control subjects (total 294 DNA samples) using PCR
      RFLP (polymerase chain reaction with following restriction fragment length
      polymorphism analysis) method. Our data showed that G-1639A but not C1173T
      polymorphism was related to IS, regardless of adjustment for age, sex, body mass
      index, smoking status, and arterial hypertension. The risk for IS in -1639A
      allele carriers (OR = 2.138, P = 0.015) was higher than in individuals with G/G
      genotype. Haplotype analysis demonstrated that -1639G/1173T and -1639A/1173C were
      related to increased risk for IS (OR = 3.813, P = 0.010, and OR = 2.189, P =
      0.011, resp.), while -1639G/1173C was a protective factor for IS (OR = 0.548, P <
      0.001). Obtained results suggested that -1639A allele can be a possible genetic
      risk factor for IS in Ukrainian population.

PMID- 27703970
TI  - Comment on "Effect of Health Education on Willingness to Undergo HIV Screening
      among Antenatal Attendees in a Teaching Hospital in North Central Nigeria".

PMID- 27703972
TI  - Corrigendum to "VGSC: A Web-Based Vector Graph Toolkit of Genome Synteny and
      Collinearity".
AB  - [This corrects the article DOI: 10.1155/2016/7823429.].

PMID- 27703969
TI  - Identification and Characterization of Small Noncoding RNAs in Genome Sequences
      of the Edible Fungus Pleurotus ostreatus.
AB  - Noncoding RNAs (ncRNAs) have been identified in many fungi. However, no genome
      scale identification of ncRNAs has been inventoried for basidiomycetes. In this
      research, we detected 254 small noncoding RNAs (sncRNAs) in a genome assembly of
      an isolate (CCEF00389) of Pleurotus ostreatus, which is a widely cultivated
      edible basidiomycetous fungus worldwide. The identified sncRNAs include snRNAs,
      snoRNAs, tRNAs, and miRNAs. SnRNA U1 was not found in CCEF00389 genome assembly
      and some other basidiomycetous genomes by BLASTn. This implies that if snRNA U1
      of basidiomycetes exists, it has a sequence that varies significantly from other
      organisms. By analyzing the distribution of sncRNA loci, we found that snRNAs and
      most tRNAs (88.6%) were located in pseudo-UTR regions, while miRNAs are commonly
      found in introns. To analyze the evolutionary conservation of the sncRNAs in P.
      ostreatus, we aligned all 254 sncRNAs to the genome assemblies of some other
      Agaricomycotina fungi. The results suggest that most sncRNAs (77.56%) were highly
      conserved in P. ostreatus, and 20% were conserved in Agaricomycotina fungi. These
      findings indicate that most sncRNAs of P. ostreatus were not conserved across
      Agaricomycotina fungi.

PMID- 27703971
TI  - The Economic Burden of Otitis Media in Korea, 2012: A Nationally Representative
      Cross-Sectional Study.
AB  - Background. Otitis media (OM) is a common communicable disease that is associated
      with a substantial economic burden. However, no Korean studies have evaluated OM
      related trends after the introduction of the pneumococcal conjugate vaccines.
      Purpose. This study aimed to estimate the prevalence and economic burden of OM in
      Korea using nationally representative data. Methods. The burden of OM was
      estimated nationally representative data such as national health insurance claims
      data from 2012, based on the prevalence approach and the societal perspective.
      Results. In 2012, 1,788,303 patients visited medical institutions for treatment
      of OM, and the prevalence and burden of OM were 3.5% and 497.35 million US
      dollars, respectively. Patients who were 0-9 years old accounted for 59.7% of the
      cases and 55.2% of the total cost. Among adults, the total and perpatient costs
      were highest among 50-59-year-old adults. Direct medical costs and outpatient
      costs accounted for large proportions of the total cost (86.3% and 88.3%, resp.).
      Conclusion. The economic burden of OM decreased after the introduction of the
      pneumococcal conjugate vaccines. However, OM is still associated with a
      relatively large burden, especially among adults, and interventions are needed to
      reduce the burden of OM in this population.

PMID- 27703973
TI  - Assessment of the Utility of the Septal E/(E' * S') Ratio and Tissue Doppler
      Index in Predicting Left Ventricular Remodeling after Acute Myocardial
      Infarction.
AB  - Background. The aim of this study is to show whether the septal E/(E' * S') ratio
      assessed by tissue Doppler echocardiography can predict left ventricular
      remodeling after first ST segment elevation myocardial infarction treated
      successfully with primary percutaneous intervention. Methods. Consecutive
      patients (n = 111) presenting with acute anterior myocardial infarction for the
      first time in their life were enrolled. All patients underwent successful primary
      percutaneous coronary intervention. Standard and tissue Doppler echocardiography
      were performed in the first 24-36 hours of admission. Echocardiographic
      examination was repeated after 6 months to reassess left ventricular volumes.
      Septal E/(E' * S') ratio was assessed by pulsed Doppler echocardiography.
      Results. Group 1 consisted of 33 patients with left ventricular (LV) remodeling,
      and Group 2 had 78 patients without LV remodeling. E/(E' * S') was significantly
      higher in Group 1 (4.1 +/- 1.9 versus 1.65 +/- 1.32, p = 0.001). The optimal
      cutoff value for E/(E' * S') ratio was 2.34 with 87.0% sensitivity and 82.1%
      specificity. Conclusion. Septal E/(E' * S') values measured after the acute
      anterior myocardial infarction can strongly predict LV remodeling in the 6-month
      follow-up. In the risk assessment, the septal E/(E' * S') can be evaluated
      together with the conventional echocardiographic techniques.

PMID- 27703974
TI  - Use of NeuroEyeCoachTM to Improve Eye Movement Efficacy in Patients with
      Homonymous Visual Field Loss.
AB  - Visual field deficits are common in patients with damaged retinogeniculostriate
      pathways. The patient's eye movements are often affected leading to inefficient
      visual search. Systematic eye movement training also called compensatory therapy
      is needed to allow patients to develop effective coping strategies. There is a
      lack of evidence-based, clinical gold-standard registered medical device
      accessible to patients at home or in clinical settings and NeuroEyeCoach (NEC) is
      developed to address this need. In three experiments, we report on performance of
      patients on NEC compared to the data obtained previously on the earlier versions
      of the search task (n = 32); we assessed whether the self-administered
      computerised tasks can be used to monitor the progress (n = 24) and compared the
      findings in a subgroup of patients to a healthy control group. Performance on
      cancellation tasks, simple visual search, and self-reported responses on
      activities of daily living was compared, before and after training. Patients
      performed similarly well on NEC as on previous versions of the therapy; the
      inbuilt functionality for pre- and postevaluation functions was sensitive to
      allowing assessment of improvements; and improvements in patients were
      significantly greater than those in a group of healthy adults. In conclusion,
      NeuroEyeCoach can be used as an effective rehabilitation tool to develop
      compensatory strategies in patients with visual field deficits after brain
      injury.

PMID- 27703975
TI  - Comment on "Toxoplasma gondii Infection in Pregnant Women: A Seroprevalence and
      Case-Control Study in Eastern China".

PMID- 27703976
TI  - Blood Pressure Response to Submaximal Exercise Test in Adults.
AB  - Background. The assessment of blood pressure (BP) response during exercise test
      is an important diagnostic instrument in cardiovascular system evaluation. The
      study aim was to determine normal values of BP response to submaximal, multistage
      exercise test in healthy adults with regard to their age, gender, and workload.
      Materials and Methods. The study was conducted in randomly selected normotensive
      subjects (n = 1015), 512 females and 498 males, aged 18-64 years (mean age 42.1
      +/- 12.7 years) divided into five age groups. All subjects were clinically
      healthy with no chronic diseases diagnosed. Exercise stress tests were performed
      using Monark bicycle ergometer until a minimum of 85% of physical capacity was
      reached. BP was measured at rest and at peak of each exercise test stage.
      Results. The relations between BP, age, and workload during exercise test were
      determined by linear regression analysis and can be illustrated by the equations:
      systolic BP (mmHg) = 0.346 * load (W) + 135.76 for males and systolic BP (mmHg) =
      0.103 * load (W) + 155.72 for females. Conclusions. Systolic BP increases
      significantly and proportionally to workload increase during exercise test in
      healthy adults. The relation can be described by linear equation which can be
      useful in diagnostics of cardiovascular diseases.

PMID- 27703978
TI  - Integrated Analysis of Multiscale Large-Scale Biological Data for Investigating
      Human Disease 2016.

PMID- 27703977
TI  - Molecular Cloning and Characterization of Full-Length cDNA of Calmodulin Gene
      from Pacific Oyster Crassostrea gigas.
AB  - The shell of the pearl oyster (Pinctada fucata) mainly comprises aragonite
      whereas that of the Pacific oyster (Crassostrea gigas) is mainly calcite, thereby
      suggesting the different mechanisms of shell formation between above two
      mollusks. Calmodulin (CaM) is an important gene for regulating the uptake,
      transport, and secretion of calcium during the process of shell formation in
      pearl oyster. It is interesting to characterize the CaM in oysters, which could
      facilitate the understanding of the different shell formation mechanisms among
      mollusks. We cloned the full-length cDNA of Pacific oyster CaM (cgCaM) and found
      that the cgCaM ORF encoded a peptide of 113 amino acids containing three EF-hand
      calcium-binding domains, its expression level was highest in the mantle, hinting
      that the cgCaM gene is probably involved in shell formation of Pacific oyster,
      and the common ancestor of Gastropoda and Bivalvia may possess at least three CaM
      genes. We also found that the numbers of some EF hand family members in highly
      calcified species were higher than those in lowly calcified species and the
      numbers of these motifs in oyster genome were the highest among the mollusk
      species with whole genome sequence, further hinting the correlation between CaM
      and biomineralization.

PMID- 27703979
TI  - A Meta-Path-Based Prediction Method for Human miRNA-Target Association.
AB  - MicroRNAs (miRNAs) are short noncoding RNAs that play important roles in
      regulating gene expressing, and the perturbed miRNAs are often associated with
      development and tumorigenesis as they have effects on their target mRNA.
      Predicting potential miRNA-target associations from multiple types of genomic
      data is a considerable problem in the bioinformatics research. However, most of
      the existing methods did not fully use the experimentally validated miRNA-mRNA
      interactions. Here, we developed RMLM and RMLMSe to predict the relationship
      between miRNAs and their targets. RMLM and RMLMSe are global approaches as they
      can reconstruct the missing associations for all the miRNA-target simultaneously
      and RMLMSe demonstrates that the integration of sequence information can improve
      the performance of RMLM. In RMLM, we use RM measure to evaluate different
      relatedness between miRNA and its target based on different meta-paths; logistic
      regression and MLE method are employed to estimate the weight of different meta
      paths. In RMLMSe, sequence information is utilized to improve the performance of
      RMLM. Here, we carry on fivefold cross validation and pathway enrichment analysis
      to prove the performance of our methods. The fivefold experiments show that our
      methods have higher AUC scores compared with other methods and the integration of
      sequence information can improve the performance of miRNA-target association
      prediction.

PMID- 27703981
TI  - Corrigendum to "miR-1-Mediated Induction of Cardiogenesis in Mesenchymal Stem
      Cells via Downregulation of Hes-1".
AB  - [This corrects the article DOI: 10.1155/2013/216286.].

PMID- 27703980
TI  - Advanced Hemodynamic Management in Patients with Septic Shock.
AB  - In patients with sepsis and septic shock, the hemodynamic management in both
      early and later phases of these "organ dysfunction syndromes" is a key
      therapeutic component. It needs, however, to be differentiated between "early
      goal-directed therapy" (EGDT) as proposed for the first 6 hours of emergency
      department treatment by Rivers et al. in 2001 and "hemodynamic management" using
      advanced hemodynamic monitoring in the intensive care unit (ICU). Recent large
      trials demonstrated that nowadays protocolized EGDT does not seem to be superior
      to "usual care" in terms of a reduction in mortality in emergency department
      patients with early identified septic shock who promptly receive antibiotic
      therapy and fluid resuscitation. "Hemodynamic management" comprises (a) making
      the diagnosis of septic shock as one differential diagnosis of circulatory shock,
      (b) assessing the hemodynamic status including the identification of therapeutic
      conflicts, and (c) guiding therapeutic interventions. We propose two algorithms
      for hemodynamic management using transpulmonary thermodilution-derived variables
      aiming to optimize the cardiocirculatory and pulmonary status in adult ICU
      patients with septic shock. The complexity and heterogeneity of patients with
      septic shock implies that individualized approaches for hemodynamic management
      are mandatory. Defining individual hemodynamic target values for patients with
      septic shock in different phases of the disease must be the focus of future
      studies.

PMID- 27703982
TI  - Styloid Process of the Temporal Bone: Morphometric Analysis and Clinical
      Implications.
AB  - Objective. To evaluate measures of the styloid process (SP) in Brazilian dry
      skulls. Methods. This study involves measurements of two points (lateral end
      posterior views) of 15 dry skulls held by the Morphology Department, Institute of
      Biological Sciences of Federal University of Minas Gerais. Results. There was a
      large variability for the length of left and right sides (in lateral and
      posterior views) of the styloid process. From the lateral view of the left and
      right styloid, the length of the SP ranged, respectively, from 10.22 mm to 69.73
      mm and from 8.30 mm to 63.77 mm. From a posterior view of the left and right
      sides of the skulls, the values range, respectively, from 15.57 mm to 69.51 mm
      and from 15.64 mm to 69.44 mm. Conclusion. We believe that this study provides
      additional information about the frequency of elongated SP among the Brazilian
      population.

PMID- 27703983
TI  - Comparing McGRATH(r) MAC, C-MAC(r), and Macintosh Laryngoscopes Operated by
      Medical Students: A Randomized, Crossover, Manikin Study.
AB  - We hypothesized that the McGRATH MAC would decrease the time of intubation
      compared to C-MAC for novices. Thirty-nine medical students who had used the
      Macintosh blade to intubate a manikin fewer than 3 times were recruited. The
      participants performed sequential intubations on the manikin in two simulated
      settings that included a normal airway and a difficult airway (tongue edema). The
      intubation time, success rate of intubation, Cormack-Lehane grade at
      laryngoscopy, and difficulty using the device were recorded. Each participant was
      asked to identify the device that was most useful. The intubation time decreased
      significantly and by a similar amount to the McGRATH MAC and C-MAC compared to
      the Macintosh blade (P < 0.001 and P = 0.017, resp.). In the difficult airway,
      the intubation times were similar among the three devices. The McGRATH MAC and C
      MAC significantly increased the success rate of intubation, improved the Cormack
      Lehane grade, and decreased the difficulty score compared to the Macintosh blade
      in both airway settings. The majority of participants selected the McGRATH MAC as
      the most useful device. The McGRATH MAC and C-MAC may offer similar benefits for
      intubation compared to the Macintosh blade in normal and difficult airway
      situations.

PMID- 27703984
TI  - Efficacy and Safety of a Permethrin-Fipronil Spot-On Solution (Effitix(r)) in
      Dogs Naturally Infested by Ticks in Europe.
AB  - Effitix is a new broad spectrum product based on the combination of fipronil 6.1%
      and permethrin 54.5% in a solution for spot-on application. It has been shown to
      be safe and efficacious in dogs in controlling tick, flea, sandfly, and mosquito
      infestations in laboratory conditions. The aim of this controlled, randomised
      study was to assess its safety and efficacy against natural tick infestations in
      field conditions. One hundred eighty-two privately owned dogs were included in
      France and Germany: 123 dogs were treated on day 0 with the permethrin-fipronil
      combination (Effitix) and 59 with a permethrin-imidacloprid combination
      (Advantix(r)). Tick counts were conducted on days 0 (before treatment), 7, 14,
      21, and 28. The percentages of efficacy on days 7, 14, 21, and 28 were,
      respectively, 91.2%, 97%, 98.3%, and 96.7% with Effitix and were 94.8%, 96.9%,
      95.7%, and 94.6% with Advantix. Very few adverse events were reported. Most were
      not serious and/or not related to the treatment with pruritus being the most
      common. One administration of Effitix was highly effective and safe to treat and
      control tick infestations for four weeks in field conditions and had a similar
      efficacy as the permethrin-imidacloprid combination for all visits.

PMID- 27703985
TI  - Developing a Conceptually Equivalent Type 2 Diabetes Risk Score for Indian
      Gujaratis in the UK.
AB  - Aims. To apply and assess the suitability of a model consisting of commonly used
      cross-cultural translation methods to achieve a conceptually equivalent Gujarati
      language version of the Leicester self-assessment type 2 diabetes risk score.
      Methods. Implementation of the model involved multiple stages, including
      pretesting of the translated risk score by conducting semistructured interviews
      with a purposive sample of volunteers. Interviews were conducted on an iterative
      basis to enable findings to inform translation revisions and to elicit
      volunteers' ability to self-complete and understand the risk score. Results. The
      pretest stage was an essential component involving recruitment of a diverse
      sample of 18 Gujarati volunteers, many of whom gave detailed suggestions for
      improving the instructions for the calculation of the risk score and BMI table.
      Volunteers found the standard and level of Gujarati accessible and helpful in
      understanding the concept of risk, although many of the volunteers struggled to
      calculate their BMI. Conclusions. This is the first time that a multicomponent
      translation model has been applied to the translation of a type 2 diabetes risk
      score into another language. This project provides an invaluable opportunity to
      share learning about the transferability of this model for translation of self
      completed risk scores in other health conditions.

PMID- 27703986
TI  - The Yin and Yang of the Opioid Growth Regulatory System: Focus on Diabetes-The
      Lorenz E. Zimmerman Tribute Lecture.
AB  - The Opioid Growth Regulatory System consists of opioid growth factor (OGF),
      [Met5]-enkephalin, and its unique receptor (OGFr). OGF inhibits cell division
      when bound to OGFr. Conversely, blockade of the interaction of OGF and OGFr,
      using the potent, long-acting opioid receptor antagonist, naltrexone (NTX),
      results in increased DNA synthesis and cell division. The authors have
      demonstrated both in vitro and in vivo that the addition of exogenous OGF or an
      increase in available OGFr decreases corneal epithelial cell division and wound
      healing. Conversely, blockade of the OGF-OGFr interaction by NTX or a decrease in
      the production of the OGFr increases corneal epithelial cell division and
      facilitates corneal epithelial wound healing. The authors also have demonstrated
      that depressed corneal and cutaneous wound healing, dry eye, and abnormal corneal
      sensitivity in type 1 and type 2 diabetes in animals can be reversed by OGF-OGFr
      blockade by NTX. Thus, the function of the Opioid Growth Regulatory System
      appears to be disordered in diabetic animals, and its function can be restored
      with NTX treatment. These studies suggest a fundamental role for the Opioid
      Growth Regulatory System in the pathobiology of diabetic complications and a need
      for studies to elucidate this role further.

PMID- 27703987
TI  - Immunomodulatory Effects of 1,25-Dihydroxyvitamin D3 on Dendritic Cells Promote
      Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens.
AB  - While emerging evidence indicates that dendritic cells (DC) play a central role
      in the pathogenesis of multiple sclerosis (MS), their modulation with
      immunoregulatory agents provides prospect as disease-modifying therapy. Our
      observations reveal that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment of
      monocyte-derived DC results in a semimature phenotype and anti-inflammatory
      cytokine profile as compared to conventional DC, in both healthy controls and MS
      patients. Importantly, 1,25(OH)2D3-treated DC induce T cell hyporesponsiveness,
      as demonstrated in an allogeneic mixed leukocyte reaction. Next, following a
      freeze-thaw cycle, 1,25(OH)2D3-treated immature DC could be recovered with a 78%
      yield and 75% viability. Cryopreservation did not affect the expression of
      membrane markers by 1,25(OH)2D3-treated DC nor their capacity to induce T cell
      hyporesponsiveness. In addition, the T cell hyporesponsiveness induced by
      1,25(OH)2D3-treated DC is antigen-specific and robust since T cells retain their
      capacity to respond to an unrelated antigen and do not reactivate upon
      rechallenge with fully mature conventional DC, respectively. These observations
      underline the clinical potential of tolerogenic DC (tolDC) to correct the
      immunological imbalance in MS. Furthermore, the feasibility to cryopreserve
      highly potent tolDC will, ultimately, contribute to the large-scale production
      and the widely applicable use of tolDC.

PMID- 27703988
TI  - Association Between Gambling and Exposure to Guns Among Cocaine-Using Women.
AB  - The purpose of this study is to assess the association between gambling severity
      and exposure to guns among substance-using women recruited in the community. Data
      for these analyses come from the baseline phase of two community-based HIV
      prevention interventions conducted among alcohol and drug-using women in St.
      Louis, MO. Gun exposure was assessed using the Violence Exposure Questionnaire
      (VEQ), and DSM-IV pathological gambling (PG) symptoms and other psychiatric
      symptoms were assessed using the Computerized Diagnostic Interview Schedule; The
      Composite International Diagnostic Interview Substance Abuse Module assessed DSM
      IV substance dependence, including cocaine dependence and alcohol dependence.
      Women in the study were predominantly African American (80%), mean age was 35.70
      years +/-8.8. Women exposed to guns were significantly more likely than women not
      exposed to guns to have gambled with all consequences: without meeting PG
      criteria (21% vs. 15%); to meet 1 to 4 PG criteria (22% vs. 12%), and to report 5
      or more PG criteria (10% vs. 5%). These differences were significant at p <
      0.0001. Based on the multivariate analysis, women who gambled without PG symptoms
      (OR = 1.77; 95% CI = 1.10-2.85) were nearly twice more likely to have exposure to
      guns than women who did not gamble. The risk for gun exposure increased with
      severity of gambling. Women who gambled and reported one to four PG criteria were
      twice as likely to have had an exposure to guns (OR 2.04; 95% CI = 1.45-3.06) and
      this risk increased to nearly threefold among women who met five or more criteria
      of PG (OR 2.65; 95% CI = 1.32-5.32). In addition, endorsing five or more criteria
      for major depressive disorder (OR 1.44; 95% CI = 1.00-2.06) and three or more
      criteria for antisocial personality adult criteria (OR 3.78; 95% CI = 2.03-7.02)
      were strong predictors for gun exposure among these women. The findings indicate
      that substance-using women with gambling behavior are at an enhanced risk to have
      exposure to guns.

PMID- 27703989
TI  - A Case of Meningococcal Pyomyositis in an Otherwise Healthy Adult.
AB  - The clinical spectrum of Neisseria meningitidis can range from nasopharyngeal
      colonization to life-threatening invasive diseases such as meningitis. However,
      its etiologic role in invasive pyomyositis (PM) has never been reported before in
      the English language. In this study, we report the first case of PM in the
      English language and the second case in the literature caused by N meningitidis.

PMID- 27703990
TI  - Candida albicans Transcriptional Profiling Within Biliary Fluid From a Patient
      With Cholangitis, Before and After Antifungal Treatment and Surgical Drainage.
AB  - We used ribonucleic acid sequencing to profile Candida albicans transcription
      within biliary fluid from a patient with cholangitis; samples were collected
      before and after treatment with fluconazole and drainage. Candida albicans
      transcriptomes at the infection site distinguished treated from untreated
      cholangitis. After treatment, 1131 C. albicans genes were differentially
      expressed in biliary fluid. Up-regulated genes were enriched in hyphal growth,
      cell wall organization, adhesion, oxidation reduction, biofilm, and fatty acid
      and ergosterol biosynthesis. This is the first study to define Candida global
      gene expression during deep-seated human infection. Successful treatment of
      cholangitis induced C. albicans genes involved in fluconazole responses and
      pathogenesis.

PMID- 27703991
TI  - Impact of a Telehealth Program That Delivers Remote Consultation and Longitudinal
      Mentorship to Community HIV Providers.
AB  - Background.  To increase human immunodeficiency virus (HIV) care capacity in our
      region, we designed a distance mentorship and consultation program based on the
      Project ECHO (Extension for Community Healthcare Outcomes) model, which uses real
      time interactive video to regularly connect community providers with a
      multidisciplinary team of academic specialists. This analysis will (1) describe
      key components of our program, (2) report types of clinical problems for which
      providers requested remote consultation over the first 3.5 years of the program,
      and (3) evaluate changes in participants' self-assessed HIV care confidence and
      knowledge over the study period. Methods.  We prospectively tracked types of
      clinical problems for which providers sought consultation. At baseline and
      regular intervals, providers completed self-efficacy assessments. We compared
      means using paired-samples t test and examined the statistical relationship
      between each survey item and level of participation using analysis of variance.
      Results.  Providers most frequently sought consultation for changing
      antiretroviral therapy, evaluating acute symptomatology, and managing mental
      health issues. Forty-five clinicians completed a baseline and at least 1 repeat
      assessment. Results demonstrated significant increase (P < .05) in participants'
      self-reported confidence to provide a number of essential elements of HIV care.
      Significant increases were also reported in feeling part of an HIV community of
      practice and feeling professionally connected to academic faculty, which
      correlated with level of program engagement. Conclusions.  Community HIV
      practitioners frequently sought support on clinical issues for which no strict
      guidelines exist. Telehealth innovation increased providers' self-efficacy and
      knowledge while decreasing professional isolation. The ECHO model creates a
      virtual network for peer-to-peer support and longitudinal mentorship, thus
      strengthening capacity of the HIV workforce.

PMID- 27703992
TI  - Deciphering the Effects of Injectable Pre-exposure Prophylaxis for Combination
      Human Immunodeficiency Virus Prevention.
AB  - Background.  A long-acting injectable formulation of rilpivirine (RPV), under
      investigation as antiretroviral pre-exposure prophylaxis (PrEP), may facilitate
      PrEP adherence. In contrast, cross-resistance between RPV and nonnucleoside
      reverse-transcriptase inhibitors comprising first-line antiretroviral therapy
      (ART) could promote human immunodeficiency virus (HIV) drug resistance and reduce
      PrEP's effectiveness. Methods.  We use novel mathematical modeling of different
      RPV PrEP scale-up strategies in KwaZulu-Natal, South Africa, to investigate their
      effects on HIV prevention and drug resistance, compared with a reference scenario
      without PrEP. Results.  Pre-exposure prophylaxis scale-up modestly increases the
      proportion of prevalent drug-resistant infections, from 33% to <=37%. The change
      in the number of prevalent drug-resistant infections depends on the interplay
      between PrEP factors (coverage, efficacy, delivery reliability, and scale-up
      strategy) and the level of cross-resistance between PrEP and ART. An optimistic
      scenario of 70% effective RPV PrEP (90% efficacious and 80% reliable delivery),
      among women aged 20-29 years, prevents 17% of cumulative infections over 10 years
      while decreasing prevalent resistance; however, prevention decreases and
      resistance increases with more conservative assumptions. Uncertainty analysis
      assuming 40%-70% cross-resistance prevalence predicts an increase in prevalent
      resistance unless PrEP's effectiveness exceeds 90%. Conclusions.  Prioritized
      scale-up of injectable PrEP among women in KwaZulu-Natal could reduce HIV
      infections, but suboptimal effectiveness could promote the spread of drug
      resistance.

PMID- 27703993
TI  - Household Clustering of Escherichia coli Sequence Type 131 Clinical and Fecal
      Isolates According to Whole Genome Sequence Analysis.
AB  - Background.  Within-household sharing of strains from the resistance-associated
      H30R1 and H30Rx subclones of Escherichia coli sequence type 131 (ST131) has been
      inferred based on conventional typing data, but it has been assessed minimally
      using whole genome sequence (WGS) analysis. Methods.  Thirty-three clinical and
      fecal isolates of ST131-H30R1 and ST131-H30Rx, from 20 humans and pets in 6
      households, underwent WGS analysis for comparison with 52 published ST131
      genomes. Phylogenetic relationships were inferred using a bootstrapped maximum
      likelihood tree based on core genome sequence polymorphisms. Accessory traits
      were compared between phylogenetically similar isolates. Results.  In the WGS
      based phylogeny, isolates clustered strictly by household, in clades that were
      distributed widely across the phylogeny, interspersed between H30R1 and H30Rx
      comparison genomes. For only 1 household did the core genome phylogeny place
      epidemiologically unlinked isolates together with household isolates, but even
      there multiple differences in accessory genome content clearly differentiated
      these 2 groups. The core genome phylogeny supported within-household strain
      sharing, fecal-urethral urinary tract infection pathogenesis (with the entire
      household potentially providing the fecal reservoir), and instances of host
      specific microevolution. In 1 instance, the household's index strain persisted
      for 6 years before causing a new infection in a different household member.
      Conclusions.  Within-household sharing of E coli ST131 strains was confirmed
      extensively at the genome level, as was long-term colonization and repeated
      infections due to an ST131-H30Rx strain. Future efforts toward surveillance and
      decolonization may need to address not just the affected patient but also other
      human and animal household members.

PMID- 27703994
TI  - Disseminated Mycobacterium chimaera Infection After Cardiothoracic Surgery.
AB  - Ten case reports of disseminated Mycobacterium chimaera infections associated
      with cardiovascular surgery were published from Europe. We report 3 cases of
      disseminated M chimaera infections with histories of aortic graft and/or valvular
      surgery within the United States. Two of 3 patients demonstrated ocular
      involvement, a potentially important clinical finding.

PMID- 27703995
TI  - Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of
      a Microbiota-Based Drug Targeted at Recurrent Clostridium difficile Infection.
AB  - Background.  Vancomycin-resistant Enterococcus (VRE) is a major healthcare
      associated pathogen and a well known complication among transplant and
      immunocompromised patients. We report on stool VRE clearance in a post hoc
      analysis of the Phase 2 PUNCH CD study assessing a microbiota-based drug for
      recurrent Clostridium difficile infection (CDI). Methods.  A total of 34 patients
      enrolled in the PUNCH CD study received 1 or 2 doses of RBX2660 (microbiota
      suspension). Patients were requested to voluntarily submit stool samples at
      baseline and at 7, 30, and 60 days and 6 months after the last administration of
      RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6
      ug/mL vancomycin and Gram staining. Vancomycin resistance was confirmed by Etest.
      Results.  VRE status (at least 1 test result) was available for 30 patients. All
      stool samples for 19 patients (63.3%, mean age 61.7 years, 68% female) tested VRE
      negative. Eleven patients (36.7%, mean age 75.5 years, 64% female) were VRE
      positive at the first test (baseline or 7-day follow-up). Of these patients,
      72.7%, n = 8 converted to negative as of the last available follow-up (30 or 60
      days or 6 months). Of the other 3: 1 died (follow-up data not available); 1
      patient remained positive at all follow-ups; 1 patient retested positive at 6
      months with negative tests during the interim. Conclusions.  Although based on a
      small sample size, this secondary analysis demonstrated the possibility of
      successfully converting a high percentage of VRE-positive patients to negative in
      a recurrent CDI population with RBX2660.

PMID- 27703996
TI  - Host Biomarkers Are Associated With Response to Therapy and Long-Term Mortality
      in Pediatric Severe Malaria.
AB  - Background.  Host responses to infection are critical determinants of disease
      severity and clinical outcome. The development of tools to risk stratify children
      with malaria is needed to identify children most likely to benefit from targeted
      interventions. Methods.  This study investigated the kinetics of candidate
      biomarkers of mortality associated with endothelial activation and dysfunction
      (angiopoietin-2 [Ang-2], soluble FMS-like tyrosine kinase-1 [sFlt-1], and soluble
      intercellular adhesion molecule-1 [sICAM-1]) and inflammation (10 kDa interferon
      gamma-induced protein [CXCL10/IP-10] and soluble triggering receptor expressed on
      myeloid cells-1 [sTREM-1]) in the context of a randomized, double-blind, placebo
      controlled, parallel-arm trial evaluating inhaled nitric oxide versus placebo as
      adjunctive therapy to parenteral artesunate for severe malaria. One hundred
      eighty children aged 1-10 years were enrolled at Jinja Regional Referral Hospital
      in Uganda and followed for up to 6 months. Results.  There were no differences
      between the 2 study arms in the rate of biomarker recovery. Median levels of Ang
      2, CXCL10, and sFlt-1 were higher at admission in children who died in-hospital
      (n = 15 of 180; P < .001, P = .027, and P = .004, respectively). Elevated levels
      of Ang-2, sTREM-1, CXCL10, and sICAM-1 were associated with prolonged clinical
      recovery times in survivors. The Ang-2 levels were also associated with
      postdischarge mortality (P < .0001). No biomarkers were associated with
      neurodisability. Conclusions.  Persistent endothelial activation and dysfunction
      predict survival in children admitted with severe malaria.

PMID- 27703997
TI  - Community-Onset Bloodstream and Other Infections, Caused by Carbapenemase
      Producing Enterobacteriaceae: Epidemiological, Microbiological, and Clinical
      Features.
AB  - Background.  Because most infections caused by carbapenemase-producing
      Enterobacteriaceae (CPE) begin during hospitalization, there are limited data
      about community-onset (CO) infections caused by CPE. Our aim is to describe the
      frequency of CO infections caused by CPE as well as the clinical features of CO
      bloodstream infections (CO-BSIs). Methods.  This study includes retrospective
      case series of CO infections caused by CPE in a tertiary hospital from January
      2010 to July 2014. Any clinical sample with a positive culture for CPE that had
      been ordered by primary care doctors or by doctors at the emergency room (ER)
      were classified as CO. Epidemiological and microbiological features of CO cases
      were assessed as were clinical features of CO-BSIs. Results.  Of 780 clinical
      samples with CPE, 180 were requested at the ER or by primary care doctors
      (22.9%), 150 of which were produced by Klebsiella pneumoniae (83.3%). The blaOXA
      48 gene was detected in 149 isolates (82.8%) followed by the blaVIM gene, 29
      (16.1%). Sixty-one patients (33.9%) had a prior history of CPE
      infection/colonization. Thirty-four of the 119 (28.6%) patients without prior
      history of CPE infection/colonization did not fulfill Friedman criteria for
      healthcare-associated infections (HAIs). Considering previous hospitalization of
      up to 12 months as a criterion for defining HAI, only 16 (13.4%) cases were
      identified as community-acquired infections. The most frequent positive sample
      was urine (133 of 180; 73.9%). Twenty-one (11.7%) patients had a BSI, 9 of them
      secondary to urinary tract infections (42.9%). Thirty-day crude mortality among
      patients with BSI was 23.8% (5 of 21). Conclusions.  Community-onset infections
      caused by CPE are an important subgroup of all CPE infections. The urinary tract
      is the main source. Bloodstream infections accounted for more than 10% of the
      cases.

PMID- 27703998
TI  - Favorable Socioeconomic Status and Recreational Polydrug Use Are Linked With
      Sexual Hepatitis C Virus Transmission Among Human Immunodeficiency Virus-Infected
      Men Who Have Sex With Men.
AB  - Background.  Sexual transmission of hepatitis C virus (HCV) among human
      immunodeficiency virus (HIV)-infected men who have sex with men (MSM) is an
      emerging issue. Studies addressing the temporal trends and risk factors
      associated with incident HCV in HIV-infected MSM in the community-based primary
      care settings in the United States are scarce. Methods.  Using a retrospective
      cohort study design, HCV incidence, defined as HCV antibody seroconversion, was
      determined in 1147 HIV-infected men receiving care at Chase Brexton Health Care
      clinics in Baltimore, Maryland between 2004 and 2014. Multivariate regression
      analyses were used to identify factors associated with incident HCV. Results. 
      There were 42 incident HCV infections during 5242 person-years (PY) of follow up
      (incidence rate [IR], 8.01/1000 PY). Thirty-seven (88%) of the incident
      infections were in MSM, of whom 31 (84%) reported no injection-drug use (IDU).
      The annual IRs for MSM were 13.1-15.8/1000 PY between 2004 and 2007, decreased to
      2.7-6.2/1000 PY between 2008 and 2011, and increased to 10.4/1000 PY and
      13.3/1000 PY in 2013 and 2014, respectively. Injection-drug use was strongly
      associated with incident HCV among all MSM (IR ratio [IRR], 14.15; P = .003);
      however, among MSM without IDU, entering care between 2010 and 2013 (IRR, 3.32; P
      = .01), being employed (IRR, 3.14; P = .03), and having a history of ulcerative
      sexually transmitted infections (IRR, 3.70; P = .009) or of polydrug use (IRR,
      5.54; P = .01) independently predicted incident HCV. Conclusions.  In this cohort
      of HIV-infected men, a re-emerging HCV epidemic was observed from 2011 to 2014
      among MSM. In addition to IDU, high-risk sexual behaviors, favorable
      socioeconomic status, and polydrug use fueled this increase in HCV infections.

PMID- 27703999
TI  - The Niche for Escherichia coli Sequence Type 131 Among Veterans: Urinary Tract
      Abnormalities and Long-Term Care Facilities.
AB  - Background.  Antimicrobial resistance among Escherichia coli is increasing,
      driven largely by the global emergence of sequence type 131 (ST131). However, the
      clinical significance of ST131 status is unknown. Among veterans, we assessed
      whether ST131 causes more severe, persistent, or recurrence-prone infections than
      non-ST131 E. coli. Methods.  Isolates were assessed by polymerase chain reaction
      for membership in ST131 and relevant subclones thereof (H30R and H30Rx) and by
      broth microdilution for susceptibility to 11 antibiotics. Clinical and
      epidemiological data were systematically abstracted from the medical record.
      Between-group comparisons were made using t tests and Fisher's exact test.
      Results.  Of the 311 unique E. coli isolates, 61 (19.6%) represented ST131. Of
      these, most (51 of 61, 83.6%) represented the H30R subclone; only 5 of 51 (9.8%)
      represented H30Rx. Relative to non-ST131 and non-H30R isolates, neither ST131 nor
      H30R were associated with more severe disease, worse clinical outcomes, or more
      robust hosts. Instead, both were more likely to be isolated from patients without
      manifestations of infection (for ST131, 36.1% vs 21.2% [P = .02]; for H30R, 39%
      vs 21% [P = .008]) and who had prior healthcare contact or long-term care
      facility (LTCF) exposure (for ST131, 33% vs 14% [P = .002]; for H30R, 37% vs 14%
      [P < .001]). Despite a greater likelihood of discordant initial therapy, outcomes
      did not differ between ST131 and H30R isolates vs other E. coli isolates.
      Conclusions.  Among veterans, ST131 and its H30R subclone were associated with
      LTCF-exposed hosts but not with worse outcomes.

PMID- 27704000
TI  - A Randomized Switch From Nevirapine-Based Antiretroviral Therapy to Single Tablet
      Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically
      Suppressed Human Immunodeficiency Virus-1-Infected Rwandans.
AB  - Background.  Many human immunodeficiency virus (HIV)-infected patients remain on
      nevirapine-based antiretroviral therapy (ART) despite safety and efficacy
      concerns. Switching to a rilpivirine-based regimen is an alternative, but there
      is little experience with rilpivirine in sub-Saharan Africa where induction of
      rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could
      potentially impact efficacy. Methods.  We conducted an open-label noninferiority
      study of virologically suppressed (HIV-1 ribonucleic acid [RNA] < 50 copies/mL)
      HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse
      transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to
      switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate
      (referenced as the Switch Arm) or continue current therapy. The primary efficacy
      endpoint was HIV-1 RNA < 200 copies/mL at week 24 assessed by the US Food and
      Drug Administration Snapshot algorithm with a noninferiority margin of 12%.
      Results.  Between April and September 2014, 184 patients were screened, and 150
      patients were enrolled; 99 patients switched to rilpivirine-emtricitabine
      tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was
      42 years and 43% of participants were women. At week 24, virologic suppression
      (HIV-1 RNA level <200 copies/mL) was maintained in 93% and 92% in the Switch Arm
      versus the continuation arm, respectively. The Switch Arm was noninferior to
      continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence
      interval, -7.5% to +12.0%). Both regimens were generally safe and well tolerated,
      although 2 deaths, neither attributed to study medications, occurred in
      participants in the Switch Arm. Conclusions.  A switch from nevirapine-based ART
      to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic
      efficacy to continued nevirapine-based ART after 24 weeks with few adverse
      events.

PMID- 27704001
TI  - Evaluation of Two Techniques for Viral Load Monitoring Using Dried Blood Spot in
      Routine Practice in Vietnam (French National Agency for AIDS and Hepatitis
      Research 12338).
AB  - Background.  Although it is the best method to detect early therapeutic failure,
      viral load (VL) monitoring is still not widely available in many resource-limited
      settings because of difficulties in specimen transfer, personnel shortage, and
      insufficient laboratory infrastructures. Dried blood spot (DBS) use, which was
      introduced in the latest World Health Organization recommendations, can overcome
      these difficulties. This evaluation aimed at validating VL measurement in DBS, in
      a laboratory without previous DBS experience and in routine testing conditions.
      Methods.  Human immunodeficiency virus (HIV)-infected adults were observed in a
      HIV care site in Hanoi, and each patient provided 2 DBS cards with whole blood
      spots and 2 plasma samples. Viral load was measured in DBS and in plasma using
      the COBAS Ampliprep/TaqMan and the Abbott RealTime assays. To correctly identify
      those with VL >= 1000 copies/mL, sensitivity and specificity were estimated.
      Results.  A total of 198 patients were enrolled. With the Roche technique, 51
      plasma VL were >=1000 copies/mL; among these, 28 presented a VL in DBS that was
      also >=1000 copies/mL (sensitivity, 54.9; 95% confidence interval [CI], 40.3
      68.9). On the other hand, all plasma VL < 1000 copies/mL were also <1000
      copies/mL in DBS (specificity, 100; 95% CI, 97.5-100). With the Abbott technique,
      45 plasma VL were >=1000 copies/mL; among these, 42 VL in DBS were also >=1000
      copies/mL (sensitivity, 93.3%; 95% CI, 81.7-98.6); specificity was 94.8 (95% CI,
      90.0-97.7). Conclusions.  The Abbott RealTime polymerase chain reaction assay
      provided adequate VL results in DBS, thus allowing DBS use for VL monitoring.

PMID- 27704002
TI  - Optimal Treatment for Complicated Intra-abdominal Infections in the Era of
      Antibiotic Resistance: A Systematic Review and Meta-Analysis of the Efficacy and
      Safety of Combined Therapy With Metronidazole.
AB  - Background.  Carbapenem-resistant Enterobacteriaceae has increased dramatically
      in the last decade, resulting in infections that are difficult to treat and
      associated with high mortality rates. To prevent further antibacterial
      resistance, it is necessary to use carbapenem selectively. A combination of
      metronidazole with an antimicrobial agent active against aerobes is an
      alternative effective treatment for patients with complicated intra-abdominal
      infections (cIAIs). This study aimed to compare efficacy and safety of
      metronidazole combination therapies and carbapenem and to provide clinical
      evidence regarding the optimal treatment of cIAI. Methods.  A systematic review
      and a meta-analysis of randomized clinical trials in the treatment of cIAI were
      conducted. The systematic review with PubMed, Embase, and the Cochrane Database
      of Systematic Reviews followed the Cochrane Handbook's recommended methodology,
      and the meta-analysis used a Mantel-Haenszel random-effects model with RevMan,
      version 5.3. Primary endpoints were clinical success and bacteriological
      eradication, and secondary endpoints were all-cause mortality and drug-related
      adverse events. Results.  Eight studies comparing metronidazole combination
      therapies and carbapenem were included in the meta-analysis. No difference was
      found between combined therapy with metronidazole and carbapenem regarding
      clinical success (odds ratio [OR] = 1.31; 95% confidence interval [CI], .75
      2.31), bacteriological eradication (OR = 1.27; 95% CI, .84-1.91), all-cause
      mortality (OR = 0.61; 95% CI, .37-1.00), or drug-related adverse events (OR =
      0.58; 95% CI, .18-1.88). Sensitivity analyses found similar results. Conclusions.
      Combined therapy with metronidazole is as effective and safe as carbapenem in
      treatment of cIAI. Therefore, combined therapy with metronidazole offers an
      effective alternative to carbapenem with low risk of drug resistance.

PMID- 27704003
TI  - Diagnosis of Capnocytophaga canimorsus Sepsis by Whole-Genome Next-Generation
      Sequencing.
AB  - We report the case of a 60-year-old man with septic shock due to Capnocytophaga
      canimorsus that was diagnosed in 24 hours by a novel whole-genome next-generation
      sequencing assay. This technology shows great promise in identifying fastidious
      pathogens, and, if validated, it has profound implications for infectious disease
      diagnosis.

PMID- 27704004
TI  - A Novel Rapidly Growing Mycobacterium Species Causing an Abdominal Cerebrospinal
      Fluid Pseudocyst Infection.
AB  - Nontuberculous mycobacteria (NTM) are a rare cause of ventriculoperitoneal shunt
      infections. We describe the isolation and identification of a novel, rapidly
      growing, nonpigmented NTM from an abdominal cerebrospinal fluid pseudocyst. The
      patient presented with fevers, nausea, and abdominal pain and clinically improved
      after shunt removal. NTM identification was performed by amplicon and whole
      genome sequencing.

PMID- 27704005
TI  - Preliminary Evaluation of a Sitafloxacin-Containing Regimen for Relapsed or
      Refractory Pulmonary Mycobacterium avium Complex Disease.
AB  - Although sitafloxacin (STFX) is known to have a favorable minimum inhibitory
      concentration for Mycobacterium avium, few studies have evaluated the clinical
      efficacy of an STFX-containing regimen for pulmonary M avium complex (MAC)
      disease. To evaluate the clinical efficacy of STFX-containing regimens for
      relapsed or refractory pulmonary MAC disease, we retrospectively reviewed 18
      patients with pulmonary MAC disease who received STFX for at least 4 weeks for
      pulmonary MAC disease between January 2008 and February 2016. Of 18 patients, 10
      (55.6%) showed improved radiological characteristics and 8 (44.4%) showed
      negative sputum cultures at 6 months. Regarding the clinical symptoms,
      improvements were observed in decreasing order in sputum production (77.8%),
      cough (72.2%), and malaise (55.6%). Common adverse events included nausea or
      vomiting (38.9%), followed by loose stool or diarrhea (27.8%) and sleepiness
      (11.1%). Although this study contained a small number of subjects, we describe a
      STFX-containing regimen that was effective in achieving sputum culture negative
      conversions and had an acceptable adverse events profile.

PMID- 27704006
TI  - Shewanella-Related Bacteremia and Fournier's Gangrene: A Case Report.
AB  - Shewanella algae and Shewanella putrefaciens have been implicated for causing
      serious infections in humans, including disseminated infection. We report the
      possible first case of Shewanella-related Fournier's gangrene and bacteremia
      caused in a 65-year-old Chinese male with nephrotic syndrome. He was successfully
      managed by surgical debridement and antibiotic therapy.

PMID- 27704007
TI  - Widespread Rift Valley Fever Emergence in Senegal in 2013-2014.
AB  - Rift Valley fever (RVF), which caused epizootics and epidemics among human and
      livestock populations, occurred in Senegal in 2013-2014. A multidisciplinary
      field investigation was carried out in 3 regions of Senegal. We found 11
      confirmed human cases of Rift Valley fever, including severe cases with
      encephalitis and retinitis, 1 pool of mosquito (Aedes ochraceus), and 52 animals
      tested positive for the disease. Symptoms such as encephalitis and macular
      retinitis were the most severe cases reported so far in Senegal. The outbreak was
      widespread due to animals' movements, leading to the largest RVF outbreak in
      Senegal in terms of geographic spreading and reaching areas that never reported
      RVF activity previously.

PMID- 27704008
TI  - Clinical Impact on Tuberculosis Treatment Outcomes of Discordance Between
      Molecular and Growth-Based Assays for Rifampin Resistance, California 2003-2013.
AB  - Background.  Data from international settings suggest that isolates of
      Mycobacterium tuberculosis with rpoB mutations testing phenotypically susceptible
      to rifampin (RIF) may have clinical significance. We analyzed treatment outcomes
      of California patients with discordant molecular-phenotypic RIF results. Methods.
      We included tuberculosis (TB) patients, during 2003-2013, whose specimens tested
      RIF susceptible phenotypically but had a rpoB mutation determined by
      pyrosequencing. Demographic data were abstracted from the California TB registry.
      Phenotypic drug-susceptibility testing, medical history, treatment, and outcomes
      were abstracted from medical records. Results.  Of 3330 isolates tested, 413
      specimens had a rpoB mutation (12.4%). Of these, 16 (3.9%) had molecular
      phenotypic discordant RIF results. Seven mutations were identified: 511Pro,
      516Phe, 526Asn, 526Ser (AGC and TCC), 526Cys, and 533Pro. Fourteen (88%) had
      isoniazid (INH) resistance, 6 of whom were also phenotypically resistant to
      ethambutol (EMB) and/or pyrazinamide (PZA). Five patients (25%), 1 with 511Pro
      and 4 with 526Asn, relapsed or failed treatment. The initial regimen for 3
      patients was RIF, PZA, and EMB; 1 patient received RIF, PZA, EMB, and a
      fluoroquinolone (FQN); and 1 patient received RIF, EMB, FQN, and some second-line
      medications. Upon retreatment with an expanded regimen, 3 (75%) patients
      completed treatment, 1 patient moved before treatment completion, and 1 patient
      continues on treatment. The remaining 11 patients had a successful outcome with 9
      having received a FQN and/or a rifamycin. Conclusions.  Rifampin molecular
      phenotypic discordance was rare, and most isolates had INH resistance. Patients
      who did not receive an expanded regimen had poor outcomes. These mutations may
      have clinical importance, and expanded treatment regimens should be considered.

PMID- 27704009
TI  - Penicillin Use in Meningococcal Disease Management: Active Bacterial Core
      Surveillance Sites, 2009.
AB  - In 2009, in the Active Bacterial Core surveillance sites, penicillin was not
      commonly used to treat meningococcal disease. This is likely because of
      inconsistent availability of antimicrobial susceptibility testing and ease of use
      of third-generation cephalosporins. Consideration of current practices may inform
      future meningococcal disease management guidelines.

PMID- 27704010
TI  - Human Immunodeficiency Virus-1 Sequence Changes and Drug Resistance Mutation
      Among Virologic Failures of Lopinavir/Ritonavir Monotherapy: AIDS Clinical Trials
      Group Protocol A5230.
AB  - Background.  The mechanism of virologic failure (VF) of lopinavir/ritonavir
      (LPV/r) monotherapy is not well understood. We assessed sequence changes in human
      immunodeficiency virus-1 reverse-transcriptase (RT) and protease (PR) regions.
      Methods.  Human immunodeficiency virus-1 pol sequences from 34 participants who
      failed second-line LPV/r monotherapy were obtained at study entry (SE) and VF.
      Sequence changes were evaluated using phylogenetic analysis and hamming distance.
      Results.  Human immunodeficiency virus-1 sequence change was higher over drug
      resistance mutation (DRM) sites (median genetic distance, 2.2%; Q1 to Q3, 2.1%
      2.5%) from SE to VF compared with non-DRM sites (median genetic distance, 1.3%;
      Q1 to Q3, 1.0%-1.4%; P < .0001). Evolution over DRM sites was mainly driven by
      changes in the RT (median genetic distance, 2.7%; Q1 to Q3, 2.2%-3.2%) compared
      with PR (median genetic distance, 1.1%; Q1 to Q3, 0.0%-1.1%; P < .0001). Most RT
      DRMs present at SE were lost at VF. At VF, 19 (56%) and 26 (76%) were susceptible
      to efavirenz/nevirapine and etravirine (ETV)/rilpivirine (RPV), respectively,
      compared with 1 (3%) and 12 (35%) at SE. Participants who retained nonnucleoside
      reverse-transcriptase inhibitor (NNRTI) DRMs and those without evolution of LPV/r
      DRMs had significantly shorter time to VF. Conclusions.  The selection of LPV/r
      DRMs in participants with longer time to VF suggests better adherence and more
      selective pressure. Fading NNRTI mutations and an increase in genotypic
      susceptibility to ETV and RPV could allow for the reuse of NNRTI. Further studies
      are warranted to understand mechanisms of PR failure.

PMID- 27704011
TI  - Implementation of an Infectious Disease Fellow-Managed Penicillin Allergy Skin
      Testing Service.
AB  - Background.  A large percentage of patients presenting to acute care facilities
      report penicillin allergies that are associated with suboptimal antibiotic
      therapy. Penicillin skin testing (PST) can clarify allergy histories but is often
      limited by access to testing. We aimed to implement an infectious diseases (ID)
      fellow-managed PST program and to assess the need for PST via national survey.
      Methods.  We conducted a prospective observational study of the implementation of
      an ID fellow-managed penicillin allergy skin testing service. The primary outcome
      of the study was to assess the feasibility and acceptability of an ID fellow
      managed PST service and its impact on the optimization of antibiotic selection.
      In addition, a survey of PST practices was sent out to all ID fellowship program
      directors in the United States. Results.  In the first 11 months of the program,
      90 patients were assessed for PST and 76 patients were tested. Of the valid
      tests, 96% were negative, and 84% with a negative test had antibiotic changes;
      63% received a narrower spectrum antibiotic, 80% received more effective therapy,
      and 61% received more cost-effective therapy. The majority of survey of
      respondents (n = 50) indicated that overreporting of penicillin allergy is a
      problem in their practice that affects antibiotic selection but listed inadequate
      personnel and time as the main barriers to PST. Conclusions.  Inpatient PST can
      be successfully managed by ID fellows, thereby promoting optimal antibiotic use
      in patients reporting penicillin allergies. This model can increase access to PST
      at institutions without adequate access to allergists while also providing an
      important educational experience to ID trainees.

PMID- 27704012
TI  - Serum Fibrosis Markers for the Diagnosis of Liver Disease Among People With
      Chronic Hepatitis C in Chennai, India.
AB  - Background.  Access to hepatitis C virus (HCV) treatment is limited in low- and
      middle-income countries (LMICs). Noninvasive biomarkers, such as fibrosis 4 (FIB
      4) and aminotransferase to platelet ratio index (APRI), are low-cost alternatives
      to staging liver disease and identifying treatment need in people with chronic
      HCV infection, but their accuracy has not been evaluated in LMICs. Methods.  We
      tested the accuracy of FIB-4 and APRI at validated cutoffs (FIB-4 <1.45, >3.25;
      APRI <0.5, >1.5) in predicting severe liver stiffness by elastography among 281
      persons chronically infected with HCV. Multivariable logistic and Cox regression
      were used to identify markers of improved prediction and mortality, respectively.
      Results.  Sensitivity and specificity of FIB-4 and APRI for predicting severe
      stiffness were 62% and 87% and 61% and 83%, respectively. Fibrosis 4 and APRI
      were less accurate in excluding significant stiffness; however, performance of
      models significantly improved with gamma-glutamyl transpeptidase (GGT) and body
      mass index (BMI) (area under receiver operating characteristic curve, 0.81; 95%
      confidence interval, .76-.87). Severe liver stiffness predicted via FIB-4 >3.25,
      APRI >1.5, and a modified FIB-4 that included GGT and BMI were significantly
      associated with increased mortality. Conclusions.  Fibrosis 4 and APRI may be
      useful in identifying individuals with severe stiffness who need treatment and
      continued monitoring in LMICs. Exclusion of significant stiffness may be improved
      by including GGT and BMI to FIB-4 models.

PMID- 27704013
TI  - Successful Treatment of Disseminated Anncaliia algerae Microsporidial Infection
      With Combination Fumagillin and Albendazole.
AB  - Anncaliia algerae myositis is a life-threatening, emerging microsporidiosis among
      immunocompromised hosts. We report a case of disseminated A algerae infection in
      a man previously treated with alemtuzumab. Due to failure of albendazole-based
      therapy, fumagillin was added as a novel approach to management, with a good
      clinical response and patient survival.

PMID- 27704014
TI  - Outpatient Antibiotic Prescribing Practices for Uncomplicated Urinary Tract
      Infection in Women in the United States, 2002-2011.
AB  - Background.  Urinary tract infection (UTI) is one of the most common diagnoses
      leading to an antibiotic prescription for women seeking ambulatory care.
      Understanding current national outpatient antibiotic prescribing practices will
      help ongoing stewardship efforts to optimize antibiotic use; however, information
      on recent national outpatient antibiotic prescribing trends for UTI is limited.
      Methods.  We analyzed the National Ambulatory Medical Care and National Hospital
      Ambulatory Medical Care Survey datasets from 2002 to 2011. Outpatient visits of
      women aged >=18 years with a diagnosis of uncomplicated UTI were included for
      analysis. We conducted weighted descriptive analyses, examined time trends in
      antibiotic prescribing, and used multivariable logistic regression to identify
      patient and provider factors associated with fluoroquinolone prescribing.
      Results.  A total of 7111 visits were identified. Eighty percent of visits
      resulted in an antibiotic prescription; fluoroquinolones were the most frequently
      prescribed antibiotics throughout the study period (49% overall). Older patients
      (adjusted odds ratio [AOR] for adults aged >=70 years = 2.5; 95% confidence
      interval [CI], 1.6-3.8) and patients treated by internists (AOR = 2.0; 95% CI,
      1.1-3.3) were more likely than younger patients and those treated by family
      practitioners to receive fluoroquinolones. Outpatient visits in the West US
      Census region were less likely to be associated with fluoroquinolone prescribing
      (AOR = 0.6; 95% CI, .4-1.0) compared with visits in the Northeast. Conclusions. 
      Fluoroquinolones were the most frequently selected antibiotic treatment for
      uncomplicated UTI in women during the study period. Outpatient antibiotic
      stewardship initiatives should include efforts to reduce overuse of
      fluoroquinolones for uncomplicated UTI.

PMID- 27704016
TI  - Point-of-Care Viral Load Testing for Sub-Saharan Africa: Informing a Target
      Product Profile.
AB  - Point-of-care viral load tests are being developed to monitor patients on
      antiretroviral therapy (ART) in sub-Saharan Africa. Test design involves trade
      offs between test attributes, including accuracy, complexity, robustness, and
      cost. We used a model of the human immunodeficiency virus epidemic and ART
      program in Zimbabwe and found that the attributes of a viral load testing
      approach that are most influential for cost effectiveness are avoidance of a high
      proportion of failed tests or results not received, use of an approach that best
      facilitates retention on ART, and the ability to facilitate greater use of
      differentiated care, including through expanding coverage of testing
      availability.

PMID- 27704015
TI  - Pediatric Kawasaki Disease and Adult Human Immunodeficiency Virus Kawasaki-Like
      Syndrome Are Likely the Same Malady.
AB  - Background.  Pediatric Kawasaki disease (KD) and human immunodeficiency virus
      (HIV)+ adult Kawasaki-like syndrome (KLS) are dramatic vasculitides with similar
      physical findings. Both syndromes include unusual arterial histopathology with
      immunoglobulin (Ig)A+ plasma cells, and both impressively respond to pooled Ig
      therapy. Their distinctive presentations, histopathology, and therapeutic
      response suggest a common etiology. Because blood is in immediate contact with
      inflamed arteries, we investigated whether KD and KLS share an inflammatory
      signature in serum. Methods.  A custom multiplex enzyme-linked immunosorbent
      assay (ELISA) defined the serum cytokine milieu in 2 adults with KLS during acute
      and convalescent phases, with asymptomatic HIV+ subjects not taking
      antiretroviral therapy serving as controls. We then prospectively collected serum
      and plasma samples from children hospitalized with KD, unrelated febrile
      illnesses, and noninfectious conditions, analyzing them with a custom multiplex
      ELISA based on the KLS data. Results.  Patients with KLS and KD subjects shared
      an inflammatory signature including acute-phase reactants reflecting tumor
      necrosis factor (TNF)-alpha biologic activity (soluble TNF receptor I/II) and
      endothelial/smooth muscle chemokines Ccl1 (Th2), Ccl2 (vascular inflammation),
      and Cxcl11 (plasma cell recruitment). Ccl1 was specifically elevated in KD versus
      febrile controls, suggesting a unique relationship between Ccl1 and KD/KLS
      pathogenesis. Conclusions.  This study defines a KD/KLS inflammatory signature
      mirroring a dysfunctional response likely to a common etiologic agent. The KD/KLS
      inflammatory signature based on elevated acute-phase reactants and specific
      endothelial/smooth muscle chemokines was able to identify KD subjects versus
      febrile controls, and it may serve as a practicable diagnostic test for KD.

PMID- 27704017
TI  - Prevalence and Outcomes of Hepatitis B Coinfection and Associated Liver Disease
      Among Antiretroviral Therapy-Naive Individuals in a Rural Tanzanian Human
      Immunodeficiency Virus Cohort.
AB  - Background.  We evaluated the prevalence of chronic hepatitis B virus (HBV)
      infection and liver fibrosis/cirrhosis in human immunodeficiency virus (HIV)
      infected individuals enrolled in a rural Tanzanian prospective cohort and
      assessed hepatic fibrosis progression 12-24 months after antiretroviral treatment
      (ART) initiation. Methods.  All ART-naive HIV-infected adults >=15-year-old
      enrolled in the Kilombero and Ulanga Antiretroviral Cohort who started ART
      between 2005 and 2015 were included. Pre-ART factors associated with significant
      liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] >1.5)
      and cirrhosis (APRI > 2.0) were identified using logistic regression. Results. 
      Of 3097 individuals screened, 227 (7.3%; 95% CI, 6.4-8.2) were hepatitis B
      surface antigen (HBsAg) positive. Before ART initiation, 9.1% individuals had
      significant liver fibrosis and 5.3% had cirrhosis. Human immunodeficiency
      virus/HBV-coinfected individuals were more likely to have an APRI score
      indicating significant fibrosis (14.2% vs 8.7%, P = .03) and cirrhosis (9.2% vs
      4.9%, P = .03) than HBV-uninfected patients. CD4 cell count <200 cell/MUL and
      alcohol consumption were independently associated with pre-ART APRI score,
      indicating significant fibrosis and cirrhosis in multivariable analyses. Among
      individuals with elevated APRI measurements pre- and 12-24 months post-ART
      initiation, 53 of 57 (93.0%) of HIV-monoinfected and 4 of 5 (80.0%) of HIV/HBV
      coinfected had a regression to APRI < 1.5. Conclusions.  Hepatic fibrosis and
      cirrhosis were common in our cohort, especially among HIV/HBV-coinfected
      individuals. The APRI improved in most patients. Pre-ART HBsAg screening and
      early onset of tenofovir-based ART for HIV/HBV-coinfection should be prioritized
      in sub-Saharan Africa.

PMID- 27704018
TI  - Insurance Status and the Risk of Severe Respiratory Syncytial Virus Disease in
      United States Preterm Infants Born at 32-35 Weeks Gestational Age.
AB  - Background.  Database studies have identified that public health insurance status
      is associated with an increased risk of severe respiratory syncytial virus (RSV)
      disease in US infants. However, these studies did not adjust for the presence of
      other risk factors and did not evaluate the risk in preterm infants. Methods.  In
      this study, we evaluate the independent association between public insurance and
      severe RSV disease outcomes adjusting for other risk factors. The prospective,
      observational RSV Respiratory Events among Preterm Infants Outcomes and Risk
      Tracking (REPORT) study was conducted over 2 consecutive RSV seasons at 188 US
      clinical sites that enrolled preterm infants born at 32-35 wGA who had not
      received RSV immunoprophylaxis with palivizumab. Adjusted incidence rates per 100
      infant-seasons of the RSV-associated endpoints of outpatient lower respiratory
      tract infection (LRI), emergency department (ED) visits, RSV hospitalizations
      (RSVHs), and intensive care unit admissions during peak RSV season (November
      March) were compared for infants with private and public insurance. Results.  Of
      1642 evaluable infants enrolled in the REPORT study, 50.1% had private insurance
      and 49.9% had public health insurance. Adjusted rates of RSV outpatient LRIs were
      similar; however, rates of ED visits (hazard ratio [HR], 2.04; 95% confidence
      interval [CI], 1.20-3.45) were higher for subjects with public insurance, with a
      similar but nonsignificant trend observed for hospitalization (HR, 1.61; 95% CI,
      .93-2.78). Conclusions.  Socioeconomic status, as evaluated by public versus
      private healthcare insurance, is a significant independent risk factor for ED use
      in US preterm infants and may contribute to increased RSVHs in this population.

PMID- 27704019
TI  - Increase in Middle East Respiratory Syndrome-Coronavirus Cases in Saudi Arabia
      Linked to Hospital Outbreak With Continued Circulation of Recombinant Virus, July
      1-August 31, 2015.
AB  - During July-August 2015, the number of cases of Middle East respiratory syndrome
      (MERS) reported from Saudi Arabia increased dramatically. We reviewed the 143
      confirmed cases from this period and classified each based upon likely
      transmission source. We found that the surge in cases resulted predominantly
      (90%) from secondary transmission largely attributable to an outbreak at a single
      healthcare facility in Riyadh. Genome sequencing of MERS coronavirus from 6 cases
      demonstrated continued circulation of the recently described recombinant virus. A
      single unique frameshift deletion in open reading frame 5 was detected in the
      viral sequence from 1 case.

PMID- 27704020
TI  - Serum Amyloid P Component and Systemic Fungal Infection: Does It Protect the Host
      or Is It a Trojan Horse?
AB  - It is a striking observation that tissue of patients invaded by the deep mycoses
      often lacks evidence of an inflammatory response. This lack of host response is
      often attributed to neutropenia secondary to chemotherapy. However, systematic
      studies do not support this simplistic explanation. However, invasive fungal
      lesions are characterized by abundant fungal functional amyloid, which in turn is
      bound by serum amyloid P component (SAP). We postulate that SAP is important in
      the local immune response in invasive fungal infections. The interaction between
      fungal functional amyloid, SAP, and the immune response in deep mycoses is
      discussed.

PMID- 27704021
TI  - Pulmonary Cryptococcosis in the Immunocompetent Patient-Many Questions, Some
      Answers.
AB  - Background.  There are no prospective data regarding the management of pulmonary
      cryptococcosis in the immunocompetent patient. Clinical guidelines recommend oral
      fluconazole for patients with mild to moderate symptoms and amphotericin B plus
      flucytosine followed by fluconazole for severe disease. It is unclear whether
      patients who have histological evidence of Cryptococcus neoformans but negative
      cultures will even respond to drug treatment. We evaluated and managed a patient
      whose presentation and course raised important questions regarding the
      significance of negative cultures, antifungal choices, duration of therapy, and
      resolution of clinical, serologic, and radiographic findings. Methods.  In
      addition to our experience, to answer these questions we reviewed available case
      reports and case series regarding immunocompetent patients with pulmonary
      cryptococcosis for the last 55 years using the following definitions: Definite -
      Clinical and/or radiographic findings of pulmonary infection and respiratory
      tract isolation of C. neoformans without other suspected etiologies; Probable -
      Clinical and radiographic findings of pulmonary infection, histopathologic
      evidence of C. neoformans, and negative fungal cultures with or without a
      positive cryptococcal polysaccharide antigen. Results.  Pulmonary cryptococcosis
      resolves in most patients with or without specific antifungal therapy. Clinical,
      radiographic, and serologic resolution is slow and may take years. Conclusions. 
      Persistently positive antigen titers are most common in untreated patients and
      may remain strongly positive despite complete or partial resolution of disease.
      Respiratory fungal cultures are often negative and may indicate nonviable
      organisms.

PMID- 27704022
TI  - Outpatient Antibiotic Prescribing Among United States Nurse Practitioners and
      Physician Assistants.
AB  - We examined US nurse practitioner (NP) and physician assistant (PA) outpatient
      antibiotic prescribing. Antibiotics were more frequently prescribed during visits
      involving NP/PA visits compared with physician-only visits, including overall
      visits (17% vs 12%, P < .0001) and acute respiratory infection visits (61% vs
      54%, P < .001). Antibiotic stewardship interventions should target NPs and PAs.

PMID- 27704023
TI  - Legionnaires' Disease Outbreak at a Resort in Cozumel, Mexico.
AB  - Background.  A Legionnaires' disease (LD) outbreak at a resort on Cozumel Island
      in Mexico was investigated by a joint Mexico-United States team in 2010. This is
      the first reported LD outbreak in Mexico, where LD is not a reportable disease.
      Methods.  Reports of LD among travelers were solicited from US health departments
      and the European Working Group for Legionella Infections. Records from the resort
      and Cozumel Island health facilities were searched for possible LD cases. In
      April 2010, the resort was searched for possible Legionella exposure sources. The
      temperature and total chlorine of the water at 38 sites in the resort were
      measured, and samples from those sites were tested for Legionella. Results.  Nine
      travelers became ill with laboratory-confirmed LD within 2 weeks of staying at
      the resort between May 2008 and April 2010. The resort and its potable water
      system were the only common exposures. No possible LD cases were identified among
      resort workers. Legionellae were found to have extensively colonized the resort's
      potable water system. Legionellae matching a case isolate were found in the
      resort's potable water system. Conclusions.  Medical providers should test for LD
      when treating community-acquired pneumonia that is severe or affecting patients
      who traveled in the 2 weeks before the onset of symptoms. When an LD outbreak is
      detected, the source should be identified and then aggressively remediated.
      Because LD can occur in tropical and temperate areas, all countries should
      consider making LD a reportable disease if they have not already done so.

PMID- 27704024
TI  - Invasive Aspergillosis Associated With Severe Influenza Infections.
AB  - Background.  Invasive aspergillosis may occur in the setting of severe influenza
      infections due to viral-induced respiratory epithelium disruption and impaired
      immune effects, but data are limited. Methods.  A retrospective study was
      conducted among severe influenza cases requiring medical intensive care unit
      (ICU) admission at an academic center during the 2015-2016 season. Data collected
      included respiratory cultures, medical conditions and immunosuppressants,
      laboratory and radiographic data, and outcomes. A systematic literature review of
      published cases in the English language of aspergillosis complicating influenza
      was conducted. Results.  Six (75%) of 8 ICU influenza cases had Aspergillus
      isolated; 5 were classified as invasive disease. No ICU patient testing negative
      for influenza infection developed aspergillosis during the study period. Among
      cases with invasive aspergillosis, influenza infection was type A (H1N1) (n = 2)
      and influenza B (n = 3). Published and current cases yielded n = 57 (European
      Organization for Research and Treatment of Cancer/Invasive Fungal Infections
      Cooperative Group and the National Institute of Allergy and Infectious Diseases
      Mycoses Study Group criteria: 37% proven, 25% probable, and 39% possible cases).
      An increasing number of cases were reported since 2010. Sixty-five percent of
      cases lacked classic underlying conditions at admission for aspergillosis, 86%
      had lymphopenia, and 46% died. Conclusions.  Aspergillosis may occur in the
      setting of severe influenza infections even among immunocompetent hosts. Risks
      may include influenza A (H1N1) or B infections and viral-induced lymphopenia,
      although further studies are needed. Prompt diagnosis and antifungal therapy are
      recommended given high mortality rates.

PMID- 27704025
TI  - Patterns of Healthcare Utilization Among Veterans Infected With Hepatitis C Virus
      (HCV) and Human Immunodeficiency Virus (HIV) and Coinfected With HIV/HCV: Unique
      Burdens of Disease.
AB  - Background.  Hepatitis C virus (HCV) infection is a leading cause of cirrhosis
      and the primary cause of liver transplantation in the United States, and
      coinfection with human immunodeficiency virus (HIV) increases the risk of
      comorbidities. However, healthcare utilization (HCU) patterns among HIV/HCV
      coinfected patients are poorly understood. This study compared the rates of HCU
      and reasons for hospital admission among HCV-infected, HIV-infected, and HIV/HCV
      coinfected veterans. Methods.  Hepatitis C virus- and HIV-infected and HIV/HCV
      coinfected veterans in care with the Department of Veterans Affairs (VA) from
      1998 to 2009 (n = 335 371, n = 28 179, n = 13 471, respectively) were identified
      by HIV- and HCV-associated International Classification of Diseases, Ninth
      Revision codes from the clinical case registry. We assessed rates of HCU using
      emergency department (ED) visits, outpatient visits, and hospitalization and
      primary diagnoses associated with hospitalization. Independent risk factors
      associated with hospitalization were also examined. Results.  Rates of outpatient
      and ED visits increased over the 11-year study period for all groups, with
      inpatient admission rates remaining stable. The HCU rates were consistently
      higher for the coinfected than other cohorts. The primary reason for hospital
      admission for all groups was psychiatric disease/substance use, accounting for
      44% of all admissions. Nadir CD4 <350 cells/mm3 was associated with higher rates
      of hospitalization versus nadir CD4 >500 cells/mm3. Conclusions.  As the current
      population of HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans age,
      they will continue to place a substantial and increasing demand on the US
      healthcare system, particularly in their utilization of ED and outpatient
      services. These data suggest the need for an ongoing investment in mental health
      and primary care within the VA healthcare system.

PMID- 27704026
TI  - Changes in Insulin Resistance After Initiation of Raltegravir or Protease
      Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s.
AB  - Background.  Antiretroviral therapy (ART) can alter glucose metabolism, but
      little data exist on the association of raltegravir (RAL) with insulin
      resistance. Methods.  A5260s was a substudy of A5257, a prospective open-label
      randomized trial in which human immunodeficiency virus (HIV)-infected treatment
      naive participants were randomized to tenofovir-emtricitabine (TDF/FTC) plus
      atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or RAL over 96 weeks.
      Baseline and changes in insulin resistance as estimated by the homeostatic model
      assessment of insulin resistance (HOMA-IR) were assessed. Wilcoxon rank-sum tests
      were used to assess shifts in the distribution of fold increase from baseline
      between treatment arms, and Spearman correlation was used to assess associations
      between HOMA-IR and measures of inflammation and body composition. Results. 
      Three hundred twenty-eight participants were randomized; 90% were male, baseline
      median age was 36, HIV ribonucleic acid copies were 4.55 log10 copies/mL, and CD4
      cell count was 349/mm3. Overall, HOMA-IR increased significantly after 4 weeks
      (1.9-fold change; 95% confidence interval, 1.73-2.05) then plateaued over the
      remainder of the study. Changes in HOMA-IR were not different between the arms (P
      >= .23). Changes in HOMA-IR were associated with changes in body mass index at
      weeks 48 and 96 (r = 0.12-0.22; P <= .04). There was a trend with increases in
      HOMA-IR and increases in visceral abdominal fat at week 96 (r = 0.12; P = .06).
      At 48 and 96 weeks, HOMA-IR correlated with interleukin-6, high-sensitivity C
      reactive protein, and soluble CD163 (r = 0.16-0.27; P <= .003). Conclusions. 
      Insulin resistance increased rapidly and then plateaued in treatment-naive
      participants initiating ART with TDF/FTC, and no differences were found with RAL
      when compared with ATV/r or DRV/r.

PMID- 27704027
TI  - Clinical Characteristics and Outcomes Among Individuals With Spinal Implant
      Infections: A Descriptive Study.
AB  - Little is known about the clinical presentation and outcomes associated with
      spinal implant infections. Here, we describe a single center's experience in a
      retrospective cohort of 109 individuals with spinal implant infections, including
      clinical, microbiological, therapeutic, and outcome data.

PMID- 27704028
TI  - CD4 Variability in Malawi: Implications for Use of a CD4 Threshold of 500
      Cells/mm3 Versus Universal Eligibility for Antiretroviral Therapy.
AB  - Background.  Given the uncertainty about the ability of a single CD4 count to
      accurately classify a patient as antiretroviral therapy (ART) eligible, we sought
      to understand the extent to which CD4 variability results in misclassification at
      a CD4 threshold of 500 cells/mm3. Methods.  We performed a prospective study of
      CD4 variability in Malawian human immunodeficiency virus-infected, ART-naive,
      World Health Organization (WHO) stage 1 or 2, nonpregnant adults. CD4 counts were
      performed daily for 8 days. We fit a Bayesian linear mixed-effects model of log
      transformed CD4 cell counts to the data. We used Monte Carlo approximations to
      estimate misclassification rates for different observed values of CD4. The
      misclassification rate was calculated based on the conditional probability of
      true CD4 given the geometric mean of observed CD4 measurements. Results.  Fifty
      patients were enrolled from 2 sites. The median age was 33.5 years (interquartile
      range, 27.5-40.0) and 34 (68%) were female. Misclassification rates were <1% when
      the observed CD4 counts were <=250 or >=750 cells/mm3. Rates of misclassification
      were high at observed CD4 counts between 350 and 650 cells/mm3, particularly when
      a single measurement was used (up to 46.7%). Conclusions.  Our data show that ART
      eligibility based on a single CD4 count results in highest risk of
      misclassification when observed CD4 counts are in the range of 350-650 cells/mm3.
      Given the benefits of early ART, countries should weigh the costs and complexity
      of CD4 testing using a 500 cell/mm3 threshold against the cost savings and public
      health benefits of universal eligibility.

PMID- 27704030
TI  - Continued Sensitivity of Plasmodium falciparum to Artemisinin in Guyana, With
      Absence of Kelch Propeller Domain Mutant Alleles.
AB  - Because of concerns about possible emergence of artemisinin resistance strains of
      Plasmodium falciparum in mining areas of the interior of Guyana, a 7-day
      artesunate trial was conducted from March to December 2014. The day-3 parasite
      clearance rate, the efficacy of artesunate at day 28, and polymorphism of Kelch
      13 (PfK13)-the marker of artemisinin resistance-were assessed. The study
      confirmed the continued sensitivity of P falciparum to artemisinin. A 7-day
      course of artesunate was 100% efficacious with only 2% (95% confidence interval,
      .1%-10.9%) of enrolled subjects positive at day 3. All day-0 parasite samples
      were wild type. Continued resistance monitoring is nevertheless recommended,
      given the widespread availability and uncontrolled use of artemisinin drugs in
      mining areas of Guyana.

PMID- 27704029
TI  - Risk Factors for Influenza A(H7N9) Disease in China, a Matched Case Control
      Study, October 2014 to April 2015.
AB  - Background.  Human infections with avian influenza A(H7N9) virus have been
      associated with exposure to poultry and live poultry markets (LPMs). We conducted
      a case-control study to identify additional and more specific risk factors.
      Methods.  Cases were laboratory-confirmed A(H7N9) infections in persons in China
      reported from October 1, 2014 to April 30, 2015. Poultry workers, those with
      insufficient data, and those refusing participation were excluded. We matched up
      to 4 controls per case by sex, age, and residential community. Using conditional
      logistic regression, we examined associations between A(H7N9) infection and
      potential risk factors. Results.  Eighty-five cases and 334 controls were
      enrolled with similar demographic characteristics. Increased risk of A(H7N9)
      infection was associated with the following: visiting LPMs (adjusted odds ratio
      [aOR], 6.3; 95% confidence interval [CI], 2.6-15.3), direct contact with live
      poultry in LPMs (aOR, 4.1; 95% CI, 1.1-15.6), stopping at a live poultry stall
      when visiting LPMs (aOR, 2.7; 95% CI, 1.1-6.9), raising backyard poultry at home
      (aOR, 7.7; 95% CI, 2.0-30.5), direct contact with backyard poultry (aOR, 4.9; 95%
      CI, 1.1-22.1), and having >=1 chronic disease (aOR, 3.1; 95% CI, 1.5-6.5).
      Conclusions.  Our study identified raising backyard poultry at home as a risk
      factor for illness with A(H7N9), suggesting the need for enhanced avian influenza
      surveillance in rural areas.

PMID- 27704031
TI  - Automatic selection of the active electrode set for image-guided cochlear implant
      programming.
AB  - Cochlear implants (CIs) are neural prostheses that restore hearing by stimulating
      auditory nerve pathways within the cochlea using an implanted electrode array.
      Research has shown when multiple electrodes stimulate the same nerve pathways,
      competing stimulation occurs and hearing outcomes decline. Recent clinical
      studies have indicated that hearing outcomes can be significantly improved by
      using an image-guided active electrode set selection technique we have designed,
      in which electrodes that cause competing stimulation are identified and
      deactivated. In tests done to date, an expert is needed to perform the electrode
      selection step with the assistance of a method to visualize the spatial
      relationship between electrodes and neural sites determined using image analysis
      techniques. We propose to automate the electrode selection step by optimizing a
      cost function that captures the heuristics used by the expert. Further, we
      propose an approach to estimate the values of parameters used in the cost
      function using an existing database of expert electrode selections. We test this
      method with different electrode array models from three manufacturers. Our
      automatic approach generates acceptable active electrode sets in 98.3% of the
      subjects tested. This approach represents a crucial step toward clinical
      translation of our image-guided CI programming system.

PMID- 27704032
TI  - Correlation between human detection accuracy and observer model-based image
      quality metrics in computed tomography.
AB  - The purpose of this study was to compare computed tomography (CT) low-contrast
      detectability from human readers with observer model-based surrogates of image
      quality. A phantom with a range of low-contrast signals (five contrasts, three
      sizes) was imaged on a state-of-the-art CT scanner (Siemens' force). Images were
      reconstructed using filtered back projection and advanced modeled iterative
      reconstruction and were assessed by 11 readers using a two alternative forced
      choice method. Concurrently, contrast-to-noise ratio (CNR), area-weighted CNR
      (CNRA), and observer model-based metrics were estimated, including
      nonprewhitening (NPW) matched filter, NPW with eye filter (NPWE), NPW with
      internal noise, NPW with an eye filter and internal noise (NPWEi), channelized
      Hotelling observer (CHO), and CHO with internal noise (CHOi). The correlation
      coefficients (Pearson and Spearman), linear discriminator error, [Formula: see
      text], and magnitude of confidence intervals, [Formula: see text], were used to
      determine correlation, proper characterization of the reconstruction algorithms,
      and model precision, respectively. Pearson (Spearman) correlation was 0.36
      (0.33), 0.83 (0.84), 0.84 (0.86), 0.86 (0.88), 0.86 (0.91), 0.88 (0.90), 0.85
      (0.89), and 0.87 (0.84), [Formula: see text] was 0.25, 0.15, 0.2, 0.25, 0.3,
      0.25, 0.4, and 0.45, and [Formula: see text] was [Formula: see text], [Formula:
      see text], [Formula: see text], [Formula: see text], [Formula: see text],
      [Formula: see text], [Formula: see text], and [Formula: see text] for CNR, CNRA,
      NPW, NPWE, NPWi, NPWEi, CHO, and CHOi, respectively.

PMID- 27704034
TI  - Communication: The formation of rarefaction waves in semiconductors after
      ultrashort excitation probed by grazing incidence ultrafast time-resolved x-ray
      diffraction.
AB  - We explore the InSb-semiconductor lattice dynamics after excitation of high
      density electron-hole plasma with an ultrashort and intense laser pulse. By using
      time resolved x-ray diffraction, a sub-mA and sub-ps resolution was achieved.
      Thus, a strain of 4% was measured in a 3 nm thin surface layer 2 ps after
      excitation. The lattice strain was observed for the first 5 ps as exponentially
      decaying, changing rapidly by time and by depth. The observed phenomena can only
      be understood assuming nonlinear time dependent laser absorption where the
      absorption depth decreases by a factor of twenty compared to linear absorption.

PMID- 27704033
TI  - Optical analysis of enamel and dentin caries in relation to mineral density using
      swept-source optical coherence tomography.
AB  - The aim of this study was to evaluate the signal intensity and signal attenuation
      of swept source optical coherence tomography (SS-OCT) for dental caries in
      relation to the variation of mineral density. SS-OCT observation was performed on
      the enamel and dentin artificial demineralization and on natural caries. The
      artificial caries model on enamel and dentin surfaces was created using
      Streptococcus mutans biofilms incubated in an oral biofilm reactor. The lesions
      were centrally cross sectioned and SS-OCT scans were obtained in two directions
      to construct a three-dimensional data set, from the lesion surface (sagittal
      scan) and parallel to the lesion surface (horizontal scan). The integrated signal
      up to [Formula: see text] in depth (IS200) and the attenuation coefficient
      ([Formula: see text]) of the enamel and dentin lesions were calculated from the
      SS-OCT signal in horizontal scans at five locations of lesion depth. The values
      were compared with the mineral density obtained from transverse microradiography.
      Both enamel and dentin demineralization showed significantly higher IS200 and
      [Formula: see text] than the sound tooth substrate from the sagittal scan. Enamel
      demineralization showed significantly higher IS200 than sound enamel, even with
      low levels of demineralization. In demineralized dentin, the [Formula: see text]
      from the horizontal scan consistently trended downward compared to the sound
      dentin.

PMID- 27704035
TI  - Time-of-flight electron energy loss spectroscopy using TM110 deflection cavities.
AB  - We demonstrate the use of two TM110 resonant cavities to generate ultrashort
      electron pulses and subsequently measure electron energy losses in a time-of
      flight type of setup. The method utilizes two synchronized microwave cavities
      separated by a drift space of 1.45 m. The setup has an energy resolution of 12 +/
      2 eV FWHM at 30 keV, with an upper limit for the temporal resolution of 2.7 +/-
      0.4 ps. Both the time and energy resolution are currently limited by the
      brightness of the tungsten filament electron gun used. Through simulations, it is
      shown that an energy resolution of 0.95 eV and a temporal resolution of 110 fs
      can be achieved using an electron gun with a higher brightness. With this, a new
      method is provided for time-resolved electron spectroscopy without the need for
      elaborate laser setups or expensive magnetic spectrometers.

PMID- 27704036
TI  - Treatment of spontaneous EAE by laquinimod reduces Tfh, B cell aggregates, and
      disease progression.
AB  - OBJECTIVE: To evaluate the influence of oral laquinimod, a candidate multiple
      sclerosis (MS) treatment, on induction of T follicular helper cells, development
      of meningeal B cell aggregates, and clinical disease in a spontaneous B cell
      dependent MS model. METHODS: Experimental autoimmune encephalomyelitis (EAE) was
      induced in C57BL/6 mice by immunization with recombinant myelin oligodendrocyte
      glycoprotein (rMOG) protein. Spontaneous EAE was evaluated in C57BL/6 MOG p35-55
      specific T cell receptor transgenic (2D2) * MOG-specific immunoglobulin (Ig)H
      chain knock-in (IgHMOG-ki [Th]) mice. Laquinimod was administered orally. T cell
      and B cell populations were examined by flow cytometry and immunohistochemistry.
      RESULTS: Oral laquinimod treatment (1) reduced CD11c+CD4+ dendritic cells, (2)
      inhibited expansion of PD-1+CXCR5+BCL6+ T follicular helper and interleukin (IL)
      21-producing activated CD4+CD44+ T cells, (3) suppressed B cell CD40 expression,
      (4) diminished formation of Fas+GL7+ germinal center B cells, and (5) inhibited
      development of MOG-specific IgG. Laquinimod treatment not only prevented rMOG
      induced EAE, but also inhibited development of spontaneous EAE and the formation
      of meningeal B cell aggregates. Disability progression was prevented when
      laquinimod treatment was initiated after mice developed paralysis. Treatment of
      spontaneous EAE with laquinimod was also associated with increases in
      CD4+CD25hiFoxp3+ and CD4+CD25+IL-10+ regulatory T cells. CONCLUSIONS: Our
      observations that laquinimod modulates myelin antigen-specific B cell immune
      responses and suppresses both development of meningeal B cell aggregates and
      disability progression in spontaneous EAE should provide insight regarding the
      potential application of laquinimod to MS treatment. Results of this
      investigation demonstrate how the 2D2 * Th spontaneous EAE model can be used
      successfully for preclinical evaluation of a candidate MS treatment.

PMID- 27704037
TI  - Targeting "bad" B cells in multiple sclerosis: Could laquinimod be part of the
      armamentarium?

PMID- 27704038
TI  - Corrigendum to "In Vivo Quantitative Ultrasound Image Analysis of Femoral
      Subchondral Bone in Knee Osteoarthritis".
AB  - [This corrects the article DOI: 10.1155/2013/182562.].

PMID- 27704039
TI  - A Prospective Observational Cohort Study on Orthopaedic and Anaesthetic
      Registrars Performing Femoral Nerve Block on Patients with an Acute Hip Fracture.
AB  - We investigated if a femoral nerve block (FNB) for patients with a proximal
      femoral fracture (PFF) and administered by an orthopaedic registrar (OR) instead
      of an anaesthesiology registrar (AR) lowers the lead time to block and reduces
      the total amount of rescue analgesics during the preoperative phase. 205 patients
      were included in a prospective observational cohort study. The main outcome
      variable was rescue analgesics as total intravenous morphine prior to surgery.
      All results were adjusted for confounding using age, sex, cognitive dysfunction,
      and ASA classification. The OR group (n = 135) was over 2 hours faster in
      performing the block compared to the AR group (n = 70) but was nonetheless
      correlated with an increased amount of rescue analgesics during the study, 2.4 mg
      morphine (95% CI 0.0-4.9) more compared to the AR group. We found no difference
      between the groups in the risk of adverse events. We conclude that, for patients
      with an acute PFF and with morphine consumption as end point, how soon from
      arrival to hospital the patients receive a FNB is of lesser importance than who
      is administering it. Based on our results we recommend that emergency hospitals
      should have routines for anaesthesiologists performing FNB on this frail patient
      group.

PMID- 27704040
TI  - Universal microbial diagnostics using random DNA probes.
AB  - Early identification of pathogens is essential for limiting development of
      therapy-resistant pathogens and mitigating infectious disease outbreaks. Most
      bacterial detection schemes use target-specific probes to differentiate pathogen
      species, creating time and cost inefficiencies in identifying newly discovered
      organisms. We present a novel universal microbial diagnostics (UMD) platform to
      screen for microbial organisms in an infectious sample, using a small number of
      random DNA probes that are agnostic to the target DNA sequences. Our platform
      leverages the theory of sparse signal recovery (compressive sensing) to identify
      the composition of a microbial sample that potentially contains novel or mutant
      species. We validated the UMD platform in vitro using five random probes to
      recover 11 pathogenic bacteria. We further demonstrated in silico that UMD can be
      generalized to screen for common human pathogens in different taxonomy levels.
      UMD's unorthodox sensing approach opens the door to more efficient and universal
      molecular diagnostics.

PMID- 27704042
TI  - Not spreading in reverse: The dewetting of a liquid film into a single drop.
AB  - Wetting and dewetting are both fundamental modes of motion of liquids on solid
      surfaces. They are critically important for processes in biology, chemistry, and
      engineering, such as drying, coating, and lubrication. However, recent progress
      in wetting, which has led to new fields such as superhydrophobicity and liquid
      marbles, has not been matched by dewetting. A significant problem has been the
      inability to study the model system of a uniform film dewetting from a nonwetting
      surface to a single macroscopic droplet-a barrier that does not exist for the
      reverse wetting process of a droplet spreading into a film. We report the
      dewetting of a dielectrophoresis-induced film into a single equilibrium droplet.
      The emergent picture of the full dewetting dynamics is of an initial regime,
      where a liquid rim recedes at constant speed and constant dynamic contact angle,
      followed by a relatively short exponential relaxation of a spherical cap shape.
      This sharply contrasts with the reverse wetting process, where a spreading
      droplet follows a smooth sequence of spherical cap shapes. Complementary
      numerical simulations and a hydrodynamic model reveal a local dewetting mechanism
      driven by the equilibrium contact angle, where contact line slip dominates the
      dewetting dynamics. Our conclusions can be used to understand a wide variety of
      processes involving liquid dewetting, such as drop rebound, condensation, and
      evaporation. In overcoming the barrier to studying single film-to-droplet
      dewetting, our results provide new approaches to fluid manipulation and uses of
      dewetting, such as inducing films of prescribed initial shapes and slip
      controlled liquid retraction.

PMID- 27704043
TI  - Depth-resolved mid-infrared photothermal imaging of living cells and organisms
      with submicrometer spatial resolution.
AB  - Chemical contrast has long been sought for label-free visualization of
      biomolecules and materials in complex living systems. Although infrared
      spectroscopic imaging has come a long way in this direction, it is thus far only
      applicable to dried tissues because of the strong infrared absorption by water.
      It also suffers from low spatial resolution due to long wavelengths and lacks
      optical sectioning capabilities. We overcome these limitations through sensing
      vibrational absorption-induced photothermal effect by a visible laser beam. Our
      mid-infrared photothermal (MIP) approach reached 10 MUM detection sensitivity and
      submicrometer lateral spatial resolution. This performance has exceeded the
      diffraction limit of infrared microscopy and allowed label-free three-dimensional
      chemical imaging of live cells and organisms. Distributions of endogenous lipid
      and exogenous drug inside single cells were visualized. We further demonstrated
      in vivo MIP imaging of lipids and proteins in Caenorhabditis elegans. The
      reported MIP imaging technology promises broad applications from monitoring
      metabolic activities to high-resolution mapping of drug molecules in living
      systems, which are beyond the reach of current infrared microscopy.

PMID- 27704041
TI  - Structure of myosin filaments from relaxed Lethocerus flight muscle by cryo-EM at
      6 A resolution.
AB  - We describe a cryo-electron microscopy three-dimensional image reconstruction of
      relaxed myosin II-containing thick filaments from the flight muscle of the giant
      water bug Lethocerus indicus. The relaxed thick filament structure is a key
      element of muscle physiology because it facilitates the reextension process
      following contraction. Conversely, the myosin heads must disrupt their relaxed
      arrangement to drive contraction. Previous models predicted that Lethocerus
      myosin was unique in having an intermolecular head-head interaction, as opposed
      to the intramolecular head-head interaction observed in all other species. In
      contrast to the predicted model, we find an intramolecular head-head interaction,
      which is similar to that of other thick filaments but oriented in a distinctly
      different way. The arrangement of myosin's long alpha-helical coiled-coil rod
      domain has been hypothesized as either curved layers or helical subfilaments. Our
      reconstruction is the first report having sufficient resolution to track the rod
      alpha helices in their native environment at resolutions ~5.5 A, and it shows
      that the layer arrangement is correct for Lethocerus. Threading separate paths
      through the forest of myosin coiled coils are four nonmyosin peptides. We suggest
      that the unusual position of the heads and the rod arrangement separated by
      nonmyosin peptides are adaptations for mechanical signal transduction whereby
      applied tension disrupts the myosin heads as a component of stretch activation.

PMID- 27704044
TI  - Giant facet-dependent spin-orbit torque and spin Hall conductivity in the
      triangular antiferromagnet IrMn3.
AB  - There has been considerable interest in spin-orbit torques for the purpose of
      manipulating the magnetization of ferromagnetic elements for spintronic
      technologies. Spin-orbit torques are derived from spin currents created from
      charge currents in materials with significant spin-orbit coupling that propagate
      into an adjacent ferromagnetic material. A key challenge is to identify materials
      that exhibit large spin Hall angles, that is, efficient charge-to-spin current
      conversion. Using spin torque ferromagnetic resonance, we report the observation
      of a giant spin Hall angle [Formula: see text] of up to ~0.35 in (001)-oriented
      single-crystalline antiferromagnetic IrMn3 thin films, coupled to ferromagnetic
      permalloy layers, and a [Formula: see text] that is about three times smaller in
      (111)-oriented films. For (001)-oriented samples, we show that the magnitude of
      [Formula: see text] can be significantly changed by manipulating the populations
      of various antiferromagnetic domains through perpendicular field annealing. We
      identify two distinct mechanisms that contribute to [Formula: see text]: the
      first mechanism, which is facet-independent, arises from conventional bulk spin
      dependent scattering within the IrMn3 layer, and the second intrinsic mechanism
      is derived from the unconventional antiferromagnetic structure of IrMn3. Using ab
      initio calculations, we show that the triangular magnetic structure of IrMn3
      gives rise to a substantial intrinsic spin Hall conductivity that is much larger
      for the (001) than for the (111) orientation, consistent with our experimental
      findings.

PMID- 27704045
TI  - Satellite tidal magnetic signals constrain oceanic lithosphere-asthenosphere
      boundary.
AB  - The tidal flow of electrically conductive oceans through the geomagnetic field
      results in the generation of secondary magnetic signals, which provide
      information on the subsurface structure. Data from the new generation of
      satellites were shown to contain magnetic signals due to tidal flow; however,
      there are no reports that these signals have been used to infer subsurface
      structure. We use satellite-detected tidal magnetic fields to image the global
      electrical structure of the oceanic lithosphere and upper mantle down to a depth
      of about 250 km. The model derived from more than 12 years of satellite data
      reveals a ~72-km-thick upper resistive layer followed by a sharp increase in
      electrical conductivity likely associated with the lithosphere-asthenosphere
      boundary, which separates colder rigid oceanic plates from the ductile and hotter
      asthenosphere.

PMID- 27704046
TI  - Energy gap evolution across the superconductivity dome in single crystals of (Ba1
      x K x )Fe2As2.
AB  - The mechanism of unconventional superconductivity in iron-based superconductors
      (IBSs) is one of the most intriguing questions in current materials research.
      Among non-oxide IBSs, (Ba1-x K x )Fe2As2 has been intensively studied because of
      its high superconducting transition temperature and fascinating evolution of the
      superconducting gap structure from being fully isotropic at optimal doping (x ~
      0.4) to becoming nodal at x > 0.8. Although this marked evolution was identified
      in several independent experiments, there are no details of the gap evolution to
      date because of the lack of high-quality single crystals covering the entire K
      doping range of the superconducting dome. We conducted a systematic study of the
      London penetration depth, lambda(T), across the full phase diagram for different
      concentrations of point-like defects introduced by 2.5-MeV electron irradiation.
      Fitting the low-temperature variation with the power law, Deltalambda ~ Tn , we
      find that the exponent n is the highest and the Tc suppression rate with disorder
      is the smallest at optimal doping, and they evolve with doping being away from
      optimal, which is consistent with increasing gap anisotropy, including an abrupt
      change around x ? 0.8, indicating the onset of nodal behavior. Our analysis using
      a self-consistent t-matrix approach suggests the ubiquitous and robust nature of
      s+/- pairing in IBSs and argues against a previously suggested transition to a d
      wave state near x = 1 in this system.

PMID- 27704047
TI  - Microbial synthesis of highly dispersed PdAu alloy for enhanced electrocatalysis.
AB  - Biosynthesis based on the reducing capacity of electrochemically active bacteria
      is frequently used in the reduction of metal ions into nanoparticles as an eco
      friendly way to recycle metal resources. However, those bionanoparticles cannot
      be used directly as electrocatalysts because of the poor conductivity of cell
      substrates. This problem was solved by a hydrothermal reaction, which also
      contributes to the heteroatom doping and alloying between Pd and Au. With the
      protection of graphene, the aggregation of nanoparticles was successfully
      avoided, and the porous structure was maintained, resulting in better
      electrocatalytic activity and durability than commercial Pd/C under both alkaline
      (CH3CH2OH, 6.15-fold of mass activity) and acidic (HCOOH, 6.58-fold of mass
      activity) conditions. The strategy developed in this work opens up a horizon into
      designing electrocatalysts through fully utilizing the abundant resources in
      nature.

PMID- 27704048
TI  - The local spiral structure of the Milky Way.
AB  - The nature of the spiral structure of the Milky Way has long been debated. Only
      in the last decade have astronomers been able to accurately measure distances to
      a substantial number of high-mass star-forming regions, the classic tracers of
      spiral structure in galaxies. We report distance measurements at radio
      wavelengths using the Very Long Baseline Array for eight regions of massive star
      formation near the Local spiral arm of the Milky Way. Combined with previous
      measurements, these observations reveal that the Local Arm is larger than
      previously thought, and both its pitch angle and star formation rate are
      comparable to those of the Galaxy's major spiral arms, such as Sagittarius and
      Perseus. Toward the constellation Cygnus, sources in the Local Arm extend for a
      great distance along our line of sight and roughly along the solar orbit. Because
      of this orientation, these sources cluster both on the sky and in velocity to
      form the complex and long enigmatic Cygnus X region. We also identify a spur that
      branches between the Local and Sagittarius spiral arms.

PMID- 27704049
TI  - Evolution of anatase surface active sites probed by in situ sum-frequency phonon
      spectroscopy.
AB  - Surface active sites of crystals often govern their relevant surface chemistry,
      yet to monitor them in situ in real atmosphere remains a challenge. Using surface
      specific sum-frequency spectroscopy, we identified the surface phonon mode
      associated with the active sites of undercoordinated titanium ions and conjoint
      oxygen vacancies, and used it to monitor them on anatase (TiO2) (101) under
      ambient conditions. In conjunction with theory, we determined related surface
      structure around the active sites and tracked the evolution of oxygen vacancies
      under ultraviolet irradiation. We further found that unlike in vacuum, the
      surface oxygen vacancies, which dominate the surface reactivity, are strongly
      regulated by ambient gas molecules, including methanol and water, as well as
      weakly associated species, such as nitrogen and hydrogen. The result revealed a
      rich interplay between prevailing ambient species and surface reactivity, which
      can be omnipresent in environmental and catalytic applications of titanium
      dioxides.

PMID- 27704051
TI  - Rescue of the 1947 Zika Virus Prototype Strain with a Cytomegalovirus Promoter
      Driven cDNA Clone.
AB  - The recent Zika virus (ZIKV) outbreak has been linked to severe pathogenesis.
      Here, we report the construction of a plasmid carrying a cytomegalovirus (CMV)
      promoter-expressed prototype 1947 Uganda MR766 ZIKV cDNA that can initiate
      infection following direct plasmid DNA transfection of mammalian cells.
      Incorporation of a synthetic intron in the nonstructural protein 1 (NS1) region
      of the ZIKV polyprotein reduced viral cDNA-associated toxicity in bacteria. High
      levels of infectious virus were produced following transfection of the plasmid
      bearing the wild-type MR766 ZIKV genome, but not one with a disruption to the
      viral nonstructural protein 5 (NS5) polymerase active site. Multicycle growth
      curve and plaque assay experiments indicated that the MR766 virus resulting from
      plasmid transfection exhibited growth characteristics that were more similar to
      its parental isolate than previously published 2010 Cambodia and 2015 Brazil cDNA
      rescued ZIKV. This ZIKV infectious clone will be useful for investigating the
      genetic determinants of ZIKV infection and pathogenesis and should be amenable to
      construction of diverse infectious clones expressing reporter proteins and
      representing a range of ZIKV isolates. IMPORTANCE The study of ZIKV, which has
      become increasingly important with the recent association of this virus with
      microcephaly and Guillain-Barre syndrome, would benefit from an efficient
      strategy to genetically manipulate the virus. This work describes a model system
      to produce infectious virus in cell culture. We created a plasmid carrying the
      prototype 1947 Uganda MR766 ZIKV genome that both was stable in bacteria and
      could produce high levels of infectious virus in mammalian cells through direct
      delivery of this DNA. Furthermore, growth properties of this rescued virus
      closely resembled those of the viral isolate from which it was derived. This
      model system will provide a simple and effective means to study how ZIKV genetics
      impact viral replication and pathogenesis.

PMID- 27704052
TI  - Different Regulations of ROM2 and LRG1 Expression by Ccr4, Pop2, and Dhh1 in the
      Saccharomyces cerevisiae Cell Wall Integrity Pathway.
AB  - Ccr4, a component of the Ccr4-Not cytoplasmic deadenylase complex, is known to be
      required for the cell wall integrity (CWI) pathway in the budding yeast
      Saccharomyces cerevisiae. However, it is not fully understood how Ccr4 and other
      components of the Ccr4-Not complex regulate the CWI pathway. Previously, we
      showed that Ccr4 functions in the CWI pathway together with Khd1 RNA binding
      protein. Ccr4 and Khd1 modulate a signal from Rho1 small GTPase in the CWI
      pathway by regulating the expression of ROM2 mRNA and LRG1 mRNA, encoding a
      guanine nucleotide exchange factor (GEF) and a GTPase-activating protein (GAP)
      for Rho1, respectively. Here we examined the possible involvement of the POP2
      gene encoding a subunit of the Ccr4-Not complex and the DHH1 gene encoding a DEAD
      box RNA helicase that associates with the Ccr4-Not complex in the regulation of
      ROM2 and LRG1 expression. Neither ROM2 mRNA level nor Rom2 function was impaired
      by pop2Delta or dhh1Delta mutation. The LRG1 mRNA level was increased in
      pop2Delta and dhh1Delta mutants, as well as the ccr4Delta mutant, and the growth
      defects caused by pop2Delta and dhh1Delta mutations were suppressed by lrg1Delta
      mutation. Our results suggest that LRG1 expression is regulated by Ccr4 together
      with Pop2 and Dhh1 and that ROM2 expression is regulated by Khd1 and Ccr4, but
      not by Pop2 and Dhh1. Thus, Rho1 activity in the CWI pathway is precisely
      controlled by modulation of the mRNA levels for Rho1-GEF Rom2 and Rho1-GAP Lrg1.
      IMPORTANCE We find here that Ccr4, Pop2, and Dhh1 modulate the levels of mRNAs
      for specific Rho1 regulators, Rom2 and Lrg1. In budding yeast, Rho1 activity is
      tightly regulated both temporally and spatially. It is anticipated that Ccr4,
      Pop2, and Dhh1 may contribute to the precise spatiotemporal control of Rho1
      activity by regulating expression of its regulators temporally and spatially. Our
      finding on the roles of the components of the Ccr4-Not complex in yeast would
      give important information for understanding the roles of the evolutionary
      conserved Ccr4-Not complex.

PMID- 27704050
TI  - Genome Diversity, Recombination, and Virulence across the Major Lineages of
      Paracoccidioides.
AB  - The Paracoccidioides genus includes two species of thermally dimorphic fungi that
      cause paracoccidioidomycosis, a neglected health-threatening human systemic
      mycosis endemic to Latin America. To examine the genome evolution and the
      diversity of Paracoccidioides spp., we conducted whole-genome sequencing of 31
      isolates representing the phylogenetic, geographic, and ecological breadth of the
      genus. These samples included clinical, environmental and laboratory reference
      strains of the S1, PS2, PS3, and PS4 lineages of P. brasiliensis and also
      isolates of Paracoccidioides lutzii species. We completed the first annotated
      genome assemblies for the PS3 and PS4 lineages and found that gene order was
      highly conserved across the major lineages, with only a few chromosomal
      rearrangements. Comparing whole-genome assemblies of the major lineages with
      single-nucleotide polymorphisms (SNPs) predicted from the remaining 26 isolates,
      we identified a deep split of the S1 lineage into two clades we named S1a and
      S1b. We found evidence for greater genetic exchange between the S1b lineage and
      all other lineages; this may reflect the broad geographic range of S1b, which is
      often sympatric with the remaining, largely geographically isolated lineages. In
      addition, we found evidence of positive selection for the GP43 and PGA1 antigen
      genes and genes coding for other secreted proteins and proteases and lineage
      specific loss-of-function mutations in cell wall and protease genes; these
      together may contribute to virulence and host immune response variation among
      natural isolates of Paracoccidioides spp. These insights into the recent
      evolutionary events highlight important differences between the lineages that
      could impact the distribution, pathogenicity, and ecology of Paracoccidioides.
      IMPORTANCE Characterization of genetic differences between lineages of the
      dimorphic human-pathogenic fungus Paracoccidioides can identify changes linked to
      important phenotypes and guide the development of new diagnostics and treatments.
      In this article, we compared genomes of 31 diverse isolates representing the
      major lineages of Paracoccidioides spp. and completed the first annotated genome
      sequences for the PS3 and PS4 lineages. We analyzed the population structure and
      characterized the genetic diversity among the lineages of Paracoccidioides,
      including a deep split of S1 into two lineages (S1a and S1b), and differentiated
      S1b, associated with most clinical cases, as the more highly recombining and
      diverse lineage. In addition, we found patterns of positive selection in surface
      proteins and secreted enzymes among the lineages, suggesting diversifying
      mechanisms of pathogenicity and adaptation across this species complex. These
      genetic differences suggest associations with the geographic range,
      pathogenicity, and ecological niches of Paracoccidioides lineages.

PMID- 27704053
TI  - Divergent Isoprenoid Biosynthesis Pathways in Staphylococcus Species Constitute a
      Drug Target for Treating Infections in Companion Animals.
AB  - Staphylococcus species are a leading cause of skin and soft tissue infections in
      humans and animals, and the antibiotics used to treat these infections are often
      the same. Methicillin- and multidrug-resistant staphylococcal infections are
      becoming more common in human and veterinary medicine. From a "One Health"
      perspective, this overlap in antibiotic use and resistance raises concerns over
      the potential spread of antibiotic resistance genes. Whole-genome sequencing and
      comparative genomics analysis revealed that Staphylococcus species use divergent
      pathways to synthesize isoprenoids. Species frequently associated with skin and
      soft tissue infections in companion animals, including S. schleiferi and S.
      pseudintermedius, use the nonmevalonate pathway. In contrast, S. aureus, S.
      epidermidis, and S. lugdunensis use the mevalonate pathway. The antibiotic
      fosmidomycin, an inhibitor of the nonmevalonate pathway, was effective in killing
      canine clinical staphylococcal isolates but had no effect on the growth or
      survival of S. aureus and S. epidermidis. These data identify an essential
      metabolic pathway in Staphylococcus that differs among members of this genus and
      suggest that drugs such as fosmidomycin, which targets enzymes in the
      nonmevalonate pathway, may be an effective treatment for certain staphylococcal
      infections. IMPORTANCE Drug-resistant Staphylococcus species are a major concern
      in human and veterinary medicine. There is a need for new antibiotics that
      exhibit a selective effect in treating infections in companion and livestock
      animals and that would not be used to treat human bacterial infections. We have
      identified fosmidomycin as an antibiotic that selectively targets certain
      Staphylococcus species that are often encountered in skin infections in cats and
      dogs. These findings expand our understanding of Staphylococcus evolution and may
      have direct implications for treating staphylococcal infections in veterinary
      medicine.

PMID- 27704054
TI  - Renal Vein Injury During Percutaneous Nephrolithotomy Procedure.
AB  - Background: Percutaneous nephrostolithotomy is an important approach for removing
      kidney stones. Puncturing and dilatation are two mandatory steps in percutaneous
      nephrolithotomy (PCNL). Uncommonly, during dilatation, the dilators can cause
      direct injury to the main renal vein or to their tributaries. Case Presentation:
      A 75-year-old female underwent PCNL for partial staghorn stone in the left
      kidney. During puncturing and dilatation, renal vein tributary was injured, and
      the nephroscope entered the renal vein and inferior vena cava, which was clearly
      recognized. Injection of contrast material through the nephroscope confirms the
      false pathway to the great veins (renal vein and inferior vena cava). Bleeding
      was controlled intraoperatively by applying Amplatz sheath over the abnormal
      tract, the procedure was continued and stones were removed. At the end of the
      procedure, a Foley catheter was used as a nephrostomy tube and its balloon was
      inflated inside the renal pelvis and pulled back with light pressure to the lower
      calix, which was the site of injury to the renal vein tributaries, then the
      nephrostomy tube was closed; by this we effectively controlled the bleeding. The
      patient remained hemodynamically stable; antegrade pyelography was done on the
      second postoperative day, there was distally patent ureter with no extravasation,
      neither contrast leak to renal vein, and was discharged home at third
      postoperative day. After 2 weeks, the nephrostomy tube was gradually removed in
      the operative room, without bleeding, on the next day, Double-J stent was
      removed. Conclusion: Direct injury and false tract to the renal vein tributaries
      during PCNL can result in massive hemorrhage, and can be treated conservatively
      in hemodynamically stable patients, using a nephrostomy catheter as a tamponade.

PMID- 27704055
TI  - Percutaneous Management of Systemic Fungal Infection Presenting As Bilateral
      Renal Fungal Ball.
AB  - Background: Zygomycoses are uncommon, frequently fatal diseases caused by fungi
      of the class Zygomycetes. The majority of human cases are caused by Mucorales
      (genus-rhizopus, mucor, and absidia) fungi. Renal involvement is uncommon and
      urine microscopy, pottasium hydroxide mount, and fungal cultures are frequently
      negative. Case Presentation: A twenty-one-year-old young unmarried lady presented
      to our emergency department with bilateral flank pain, fever, nausea, and
      decreased urine output of one-month duration. She was found to have azotemia with
      sepsis with bilateral hydronephrosis with a left renal pelvic obstructing stone.
      Even after nephrostomy drainage and broad spectrum antibiotics, her condition
      worsened. She developed disseminated fungal infection, and timely systemic
      antifungal followed by bilateral nephroscopic clearance saved the patient.
      Conclusion: Although renal fungal infections are uncommon, a high index of
      suspicion and early antifungal and surgical intervention can give favorable
      outcomes.

PMID- 27704056
TI  - Endoureteral Management of Renal Graft Ureteral Stenosis by the Use of Long-Term
      Metal Stent: An Appealing Treatment Option.
AB  - Background: Ureteral stenosis is part of the common complications of renal graft
      reported in 3% to 7% of cases. Multiple treatments have been introduced regarding
      length and position of the stenosis. Metal stents for urologic purpose were
      created in 1998. Double percutaneous antegrade and transurethral retrograde
      access to a ureteral stenosis to a long-term metal stent procedure has been
      rarely described. Case Presentation: Here, we present a case of a ureteral
      stricture in a double ipsilateral kidney graft with a common ureter. A 67-year
      old patient presented with obstructive nephritis associated with acute renal
      failure 6 years after a double renal graft with a uretero-ureteral end-to-side
      anastomosis. Abdominal CT scan showed double pelvic dilation. The patient
      underwent double percutaneous nephrostomies and antegrade pyelogram showed both
      renal pelvic and ureter dilations caused by a severe chronic ureteral stenosis at
      junction into the bladder. A Double-J ureteric stent was then inserted
      retrogradely over a guidewire as first-line treatment. Due to recurrent urinary
      tract infections (UTIs), removal and replacement of Double-J stents were carried
      out by placing a thermoexpandable metal stent Memokath(r) 051 (Bard, Pnn Medical)
      through the common ureter by a double antegrade and retrograde approach.
      Treatment was effective with a good renal function maintained after a 3-year
      follow-up without UTIs. Conclusion: Double antegrade and retrograde access to a
      long-term metal stent treatment can be seen as an alternative treatment to either
      endoscopy or open surgery. Further studies should be continued using larger
      series.

PMID- 27704057
TI  - Sulfadiazine-Induced Obstructive Nephropathy Presenting with Upper Urinary Tract
      Extravasation.
AB  - Background: Obstructive nephropathy is an uncommon side effect of sulfadiazine,
      which is used for the treatment of toxoplasmosis. We present a case of acute
      renal colic and urine extravasation of a patient shortly after she was started on
      this medication. Case Presentation: A 31-year-old female presented with acute
      renal colic 2 weeks after starting treatment with sulfadiazine and pyrimethamine
      for ocular toxoplasmosis. Results: A noncontrast computed tomography revealed
      left hydronephrosis and fluid located around the kidney and in the left gutter.
      There were no urinary stones. Administration of intravenous contrast revealed
      significant urine extravasation at the level of the ureteropelvic junction.
      Intravenous contrast injection confirmed that the extravasation consisted of
      urine leakage at the ureteropelvic junction. Her clinical condition improved with
      the insertion of an internal stent, which was left in place for 4 weeks. A
      retrograde pyelography performed at the time of the internal stent removal ruled
      out persistent extravasation and filling defects in the left upper urinary tract.
      Considering the clinical circumstances and the imaging results, it appears that
      this is a first reported case of sulfadiazine-induced obstructive uropathy
      associated with urine extravasation. Conclusion: Although rare, obstructive
      uropathy related to sulfadiazine medication should be promptly suspected,
      diagnosed, and treated. Patients should be instructed to substantially increase
      their liquid intake while on that medication.

PMID- 27704058
TI  - Arabidopsis thaliana microRNA162 level is posttranscriptionally regulated via
      splicing and polyadenylation site selection.
AB  - Arabidopsis microRNA162 (miRNA162) level regulation was studied under abiotic
      stresses, such as drought and salinity. The TaqMan(r) microRNA assay proved that
      A. thaliana miRNA162 level was elevated under these stresses, confirming its salt
      and drought responsiveness. The promoter region analyses of A. thaliana miRNA162a
      and b genes (MIR162a and MIR162b) identified numerous salinity and drought
      responsive elements. However, our results indicated that Arabidopsis MIR162a was
      presumably the main locus responsible for the mature ath-miRNA162 accumulation
      under the stresses tested, and the MIR162b was generally rather weakly expressed,
      both in control and under the stress conditions. The MIR162a structure was
      confirmed to be complex and the pri-miRNA162a hairpin structure was shown to span
      an alternative exon and an intron. The MIR162a transcription generated a few pri
      miRNA162a splicing isoforms that could be functional and non-functional. Upon
      drought and salinity stresses, the regulation of the pri-miRNA162a alternative
      splicing pattern revealed an increase of a functional pri-miR162a isoform and a
      preferential distal polyA site selection under the stress conditions. Apart from
      the potential transcriptional regulation of the miRNA genes (MIRs) expression,
      the data obtained point to an essential role of posttranscriptional regulation of
      Arabidopsis microRNA162 level.

PMID- 27704059
TI  - Inorganic perovskite photocatalysts for solar energy utilization.
AB  - The development and utilization of solar energy in environmental remediation and
      water splitting is being intensively studied worldwide. During the past few
      decades, tremendous efforts have been devoted to developing non-toxic, low-cost,
      efficient and stable photocatalysts for water splitting and environmental
      remediation. To date, several hundreds of photocatalysts mainly based on metal
      oxides, sulfides and (oxy)nitrides with different structures and compositions
      have been reported. Among them, perovskite oxides and their derivatives (layered
      perovskite oxides) comprise a large family of semiconductor photocatalysts
      because of their structural simplicity and flexibility. This review specifically
      focuses on the general background of perovskite and its related materials,
      summarizes the recent development of perovskite photocatalysts and their
      applications in water splitting and environmental remediation, discusses the
      theoretical modelling and calculation of perovskite photocatalysts and presents
      the key challenges and perspectives on the research of perovskite photocatalysts.

PMID- 27704060
TI  - Tuning two-dimensional nanomaterials by intercalation: materials, properties and
      applications.
AB  - 2D materials have attracted tremendous attention due to their unique physical and
      chemical properties since the discovery of graphene. Despite these intrinsic
      properties, various modification methods have been applied to 2D materials that
      yield even more exciting results in terms of tunable properties and device
      performance. Among all modification methods, intercalation of 2D materials has
      emerged as a particularly powerful tool: it provides the highest possible doping
      level and is capable of (ir)reversibly changing the phase of the material.
      Intercalated 2D materials exhibit extraordinary electrical transport as well as
      optical, thermal, magnetic, and catalytic properties, which are advantageous for
      optoelectronics, superconductors, thermoelectronics, catalysis and energy storage
      applications. The recent progress on host 2D materials, various intercalation
      species, and intercalation methods, as well as tunable properties and potential
      applications enabled by intercalation, are comprehensively reviewed.

PMID- 27704061
TI  - Theoretical prediction of coordination environments and stability constants of
      lanthanum lactate complexes in solution.
AB  - Using Density Functional Theory calculations in combination with explicit solvent
      and a continuum solvent model, this work sets out to understand the coordination
      environment and relevant thermodynamics of La(iii)-lactate complexes.
      Calculations focus on the coordination modes for the complexes and changes in
      Gibbs free energy for complexation in solution. These results confirm that the
      alpha-hydroxyl group should be protonated, or at least hydrogen bonded to a water
      molecule, upon successive addition of the lactate ligand to the La(iii) center
      using Bader's Atoms-in Molecules (AIM) approach. In addition, we present a
      straightforward method for predicting stability constants at the semi
      quantitative level for La(iii)-lactate complexes in solution. The proposed method
      could be particularly useful for prediction of lanthanide complex formation in
      various biochemical, environmental, and nuclear separations processes.

PMID- 27704066
TI  - The potential beneficial effects of phenolic compounds isolated from A. pilosa
      Ledeb on insulin-resistant hepatic HepG2 cells.
AB  - Agrimonia pilosa Ledeb (AP) has already been applied in practice for the
      treatment of different disorders and is available to access without the provision
      of a medical prescription. The present study aims at investigating the effect of
      bioactive compounds isolated from AP on the improvement of insulin resistance,
      figuring out the mechanism in insulin-responsive cell lines. Five compounds were
      isolated from AP using column chromatography, including agrimonolide (K1),
      desmethylagrimonolide (K2), tormentic acid (K3), ursolic acid (K4), and quercetin
      (K5). Glucose metabolism was evaluated in insulin-resistant HepG2 cells. Ursolic
      acid had the strongest activity among all isolated compounds with the lowering
      value of 71.5% (1.24 mM glucose in DMEM) and 71.7% (1.23 mM) when compared to the
      control. K1 consisting of K2 effectively increased the insulin-mediated glycogen
      level in hepatocytes. At a concentration level of 20 MUM, K2 significantly
      elevated the hepatic glucokinase (GK) activity (3.2 U min-1 mg-1 protein),
      followed by K1 (3.0 U min-1 mg-1 protein). Both of them significantly increased
      (p < 0.05) the GK activity as compared to the control. On the same lines, K2 and
      K1 caused a significant reduction of the glucose-6-phosphatase (G6Pase) activity
      and a significant change in the phosphoenolpyruvate carboxykinase (PEPCK)
      activity. In summary, bioactive compounds in AP may play an important role in
      regulating the glucose metabolism in insulin-resistant HepG2 cells and could be
      developed as a promising natural material for diabetes prevention and treatment.

PMID- 27704067
TI  - Mid-infrared fibre evanescent wave spectroscopy of serum allows fingerprinting of
      the hepatic metabolic status in mice.
AB  - Non-alcoholic fatty liver disease is associated with obesity, diabetes, and
      metabolic syndrome. The detection of systemic metabolic changes associated with
      alterations in the liver status during non-alcoholic fatty liver disease could
      improve patient follow-up. The aim of the present study was to evaluate the
      potential of mid-infrared fibre evanescent wave spectroscopy as a minimum
      invasive method for evaluating the liver status during non-alcoholic fatty liver
      disease. Seventy-five mice were subjected to a control, high-fat or high-fat-high
      carbohydrate diets. We analysed the serum biochemical parameters and mRNA levels
      of hepatic genes by quantitative RT-PCR. Steatosis was quantified by image
      analysis. The mid-infrared spectra were acquired from serum, and then analysed to
      develop a predictive model of the steatosis level. Animals subjected to enriched
      diets were obese. Hepatic steatosis was found in all animals. The relationship
      between the spectroscopy-predicted and observed levels of steatosis, expressed as
      percentages of the liver biopsy area, was not linear. A transition around 10%
      steatosis was observed, leading us to consider two distinct predictive models
      (<10% and >10%) based on two different sets of discriminative spectral variables.
      The model performance was evaluated using random cross-validation (10%). The
      hypothesis that additional metabolic changes occur beyond this transition was
      supported by the fact that it was associated with increased serum ALT levels, and
      Col1alpha1 chain mRNA levels. Our data suggest that mid-infrared spectroscopy
      combined with statistical analysis allows identifying serum mid-infrared
      signatures that reflect the liver status during non-alcoholic fatty liver
      disease.

PMID- 27704068
TI  - Recent developments in polydopamine: an emerging soft matter for surface
      modification and biomedical applications.
AB  - After more than four billion years of evolution, nature has created a large
      number of fascinating living organisms, which show numerous peculiar structures
      and wonderful properties. Nature can provide sources of plentiful inspiration for
      scientists to create various materials and devices with special functions and
      uses. Since Messersmith proposed the fabrication of multifunctional coatings
      through mussel-inspired chemistry, this field has attracted considerable
      attention for its promising and exiciting applications. Polydopamine (PDA), an
      emerging soft matter, has been demonstrated to be a crucial component in mussel
      inspired chemistry. In this review, the recent developments of PDA for mussel
      inspired surface modification are summarized and discussed. The biomedical
      applications of PDA-based materials are also highlighted. We believe that this
      review can provide important and timely information regarding mussel-inspired
      chemistry and will be of great interest for scientists in the chemistry,
      materials, biology, medicine and interdisciplinary fields.

PMID- 27704070
TI  - Sensitive fluorescence detection of mercury(ii) in aqueous solution by the
      fluorescence quenching effect of MoS2 with DNA functionalized carbon dots.
AB  - A rapid and sensitive fluorescent sensor based on the MoS2 nanosheet/DNA/carbon
      dot nanoassembly has been developed towards the detection of mercury(ii) present
      in environmental samples. Bio-carbon dots (CDs) having strong fluorescence maxima
      at 451 nm were synthesized via one-step treatment with honey under low
      temperature carbonization. These CDs were nearly spherical with good size
      distribution and excellent monodispersity, and the average sizes of CD were
      around 2-4 nm as evidenced from transmission electron microscopy. The conjugation
      of DNA strands on the surface of the carbon dots provided an efficient
      fluorescent probe. The fluorescence of the MoS2 nanosheet/DNA/carbon dot
      nanoassembly enhanced gradually with the increase in the concentration of Hg2+
      ions and the detection limit was found to be 1.02 nM. Furthermore, the
      fluorescence intensity was found to be linear with the concentration of Hg2+ ions
      in the range from 0 to 10 nM and their respective coefficient of determination
      was found to be 0.93676 and 0.98178. The present MoS2 nanosheet/DNA/carbon dot
      nanoassembly is highly selective toward Hg2+ ions over a wide range of metal ions
      tested.

PMID- 27704069
TI  - Orientational binding modes of reporters in a viral-nanoparticle lateral flow
      assay.
AB  - Using microscopy and image analysis, we characterize binding of filamentous viral
      nanoparticles to a fibrous affinity matrix as models for reporter capture in a
      lateral flow assay (LFA). M13 bacteriophage (M13) displaying an in vivo
      biotinylated peptide (AviTag) genetically fused to the M13 tail protein p3 are
      functionalized with fluorescent labels. We functionalize glass fiber LFA
      membranes with antibodies to M13, which primarily capture M13 on the major p8
      coat proteins, or with avidin, which captures M13 at the biotin-functionalized
      tail, and compare orientational modes of reporter capture for the side- versus
      tip-binding recognition interactions. The number of captured M13 is greater for
      side-binding than for tip-binding, as expected from the number of recognition
      groups. Whereas two-thirds of side-bound M13 captured by an anti-M13 antibody
      bind immediately after colliding with the membrane, tip-bound M13 prominently
      exhibit three additional orientational modes that require M13 to reorient to
      enable binding. These results are consistent with the idea that the elongated M13
      shape couples with the complex flow field in an open and disordered fibrous LFA
      membrane to enhance capture.

PMID- 27704071
TI  - Rapid acquisition of mean Raman spectra of eukaryotic cells for a robust single
      cell classification.
AB  - Raman spectroscopy has previously been used to identify eukaryotic and
      prokaryotic cells. While prokaryotic cells are small in size and can be assessed
      by a single Raman spectrum, the larger size of eukaryotic cells and their complex
      organization requires the acquisition of multiple Raman spectra to properly
      characterize them. A Raman spectrum from a diffraction-limited spot at an
      arbitrary location within a cell results in spectral variations that affect
      classification approaches. To probe whole cells with Raman imaging at high
      spatial resolution is time consuming, because a large number of Raman spectra
      need to be collected, resulting in low cell throughput and impairing statistical
      analysis due to low cell numbers. Here we propose a method to overcome the
      effects of cellular heterogeneity by acquiring integrated Raman spectra covering
      a large portion of a cell. The acquired spectrum represents the mean
      macromolecular composition of a cell with an exposure time that is comparable to
      acquisition of a single Raman spectrum. Data sets were collected from T
      lymphocyte Jurkat cells, and pancreatic cell lines Capan1 and MiaPaca2. Cell
      classification by support vector machines was compared for single spectra,
      spectra of images and integrated Raman spectra of cells. The integrated approach
      provides better and more stable prediction for individual cells, and in the
      current implementation, the mean macromolecular information of a cell can be
      acquired faster than with the acquisition of individual spectra from a comparable
      region. It is expected that this approach will have a major impact on the
      implementation of Raman based cell classification.

PMID- 27704072
TI  - Recent advances in the chemical imaging of human fingermarks (a review).
AB  - This review highlights the considerable advances in the chemical imaging of human
      fingermarks that provide more chemical information, including numerous endogenous
      and exogenous constituents. Despite remarkable development in DNA analysis and
      recognition, human fingermark analysis remains one of the priority approaches
      available for obtaining reliable forensic evidence. Additional information about
      the donor can be obtained from the chemical composition of latent fingermarks in
      addition to the ridge pattern, such as the age, gender, medical history, and
      possible drug habits. The analytical approaches reviewed here include
      spectroscopy, mass spectrometry, immuno-labelling and electrochemical methods.
      Each method has different capabilities with respect to sensitivity,
      reproducibility, selectivity, reliability and ultimately applicability, either
      for use in routine forensic practice or in academic research work. The advantages
      of spectroscopic techniques, including infrared, Raman and micro-X-ray
      fluorescence spectroscopy, are the capabilities of a rapid and non-destructive
      imaging of fingermarks by providing spectral information on chemical composition.
      In addition, mass spectrometry imaging can provide spatially specific information
      on fingermark chemical composition. Recently, the use of immuno-labelling in
      latent fingermark detection has attracted significant attention because it can
      overcome the sensitivity and selectivity problems experienced with other existing
      methods. The electrochemical method has also been employed to image latent
      fingermarks by measuring the electric current changes with the spatial chemical
      composition from the ridges and valleys at high resolution to provide a third
      level of detail, which is especially useful for multicoloured background surfaces
      or for surfaces contaminated with blood or other bodily fluids.

PMID- 27704073
TI  - Development of a protease-resistant reporter to quantify BCR-ABL activity in
      intact cells.
AB  - A peptidase-resistant ABL kinase substrate was developed by identifying protease
      susceptible bonds on an ABL substrate peptide and replacing flanking amino acids
      with non-native amino acids. After an iterative design process, the lead, or
      designed, peptide X-A possesses a six-fold longer life in a cytosolic lysate than
      that of the starting peptide. The catalytic efficiency (kcat/KM) of purified ABL
      kinase for the lead peptide (125 s-1 MUM-1) is similar to that of the starting
      peptide (103 s-1 MUM-1) demonstrating preservation of the peptide's ability to
      serve as a kinase substrate. When incubated in cytosolic lysates, the lead
      peptide is slowly degraded into 4 fragments over time. In contrast, when loaded
      into intact cells, the peptide is metabolized into 5 fragments, with only 2 of
      the fragments corresponding to those in the lysate. Thus the two environments
      possess differing peptidase activities, which must be accounted for when
      designing peptidase-resistant peptides. In both settings, the substrate is
      phosphorylated by BCR-ABL providing a readout of BCR-ABL activity. A small panel
      of tyrosine kinase inhibitors verified the substrate's specificity for BCR
      ABL/ABL kinase activity in both lysates and cells in spite of the multitude of
      other kinases present. The designed peptide X-A acts as a long-lived BCR-ABL
      kinase reporter in the leukemic cells possessing the BCR-ABL mutation.

PMID- 27704074
TI  - Signal amplification of microRNAs with modified strand displacement-based cycling
      probe technology.
AB  - Micro ribose nucleic acids (miRNAs) play an important role in biological
      processes such as cell differentiation, proliferation and apoptosis. Therefore,
      miRNAs are potentially a powerful marker for monitoring cancer and diagnosis.
      Here, we present sensitive signal amplification for miRNAs based on modified
      cycling probe technology with strand displacement amplification. miRNA was
      captured by the template coupled with beads, and then the first cycle based on
      SDA was repeatedly extended to the nicking end, which was produced by the
      extension reaction of miRNA. The products generated by SDA are captured by a
      molecular beacon (MB), which is designed to initiate the second amplification
      cycle, with a similar principle to the cycling probe technology (CPT), which is
      based on repeated digestion of the DNA-RNA hybrid by the RNase H. After one
      sample enrichment and two steps of signal amplification, 0.1 pM of let-7a can be
      detected. The miRNA assay exhibits a great dynamic range of over 100 orders of
      magnitude and high specificity to clearly discriminate a single base difference
      in miRNA sequences. This isothermal amplification does not require any special
      temperature control instrument. The assay is also about signal amplification
      rather than template amplification, therefore minimising contamination issues. In
      addition, there is no need for the reverse transcription (RT) process. Thus the
      amplification is suitable for miRNA detection.

PMID- 27704075
TI  - A DNA array based on clickable lesion-containing hairpin probes for multiplexed
      detection of base excision repair activities.
AB  - DNA is under continuous assault by environmental and endogenous reactive oxygen
      and alkylating species, inducing the formation of mutagenic, toxic and genome
      destabilizing nucleobase lesions. Due to the implications of such genetic
      alterations in cell death, aging, inflammation, neurodegenerative diseases and
      cancer, many efforts have been devoted to developing assays that aim at analyzing
      DNA repair activities from purified enzymes or cell extracts. The present work
      deals with the conception and application of a new, miniaturized and parallelized
      on surface-DNA biosensor to measure base excision repair (BER) activities. Such a
      bio-analytical tool was built by using the "click chemistry" approach to
      immobilize, on a glass slide, fluorescent stem-loop DNA probes, which contain a
      specific nucleobase lesion. The performance of this new high-throughput DNA
      repair analysis technology was determined by detecting uracil N-glycosylase and
      AP-endonuclease activities from purified enzymes or in cell extracts. The
      applications of this device were extended to analyze, in cell extracts, the
      ability of two inhibitors (Uracil glycosylase inhibitor (Ugi) and methoxyamine
      (MX)) to block the excision of uracil and the cleavage of AP sites, respectively.
      Altogether, our results show that this new fluorescent DNA microarray platform
      provides an easy, rapid and robust method for detecting DNA N-glycosylase and AP
      endonuclease activities and evaluating the effects of BER inhibitors in a
      multiplexed fashion.

PMID- 27704076
TI  - A rapid SERS method for label-free bacteria detection using polyethylenimine
      modified Au-coated magnetic microspheres and Au@Ag nanoparticles.
AB  - A rapid, sensitive, and label-free SERS detection method for bacteria pathogens
      is reported for the first time. The method, which is based on the combination of
      polyethylenimine (PEI)-modified Au-coated magnetic microspheres (Fe3O4@Au@PEI)
      and concentrated Au@Ag nanoparticles (NPs), was named the capture-enrichment
      enhancement (CEE) three-step method. A novel Fe3O4@Au microsphere with
      monodispersity and strong magnetic responsiveness was synthesized as a magnetic
      SERS substrate and amino functionalized by PEI self-assembly. The negatively
      charged bacteria were quickly captured and enriched by the positively charged
      Fe3O4@Au@PEI microspheres, and the bacteria SERS signal was synergistically
      enhanced by using Fe3O4@Au@PEI microspheres and Au@Ag NPs in conjunction. The CEE
      three-step method proved useful in tap water and milk samples, and the total
      assay time required was only 10 min. Results further demonstrated that the CEE
      three-step method could be a common approach for detecting a wide range of
      bacteria, as verified by its detection of the Gram-positive bacterium E. coli and
      Gram-positive bacterium S. aureus at a detection limit of as low as 103 cells per
      mL. Therefore, our CEE three-step method offered the significant advantages of
      short assay time, simple operating procedure, and higher sensitivity than
      previously reported methods of SERS-based bacteria detection.

PMID- 27704077
TI  - Comparing surface properties of melanoma cells using time of flight secondary
      ions mass spectrometry.
AB  - Various techniques have been already reported to differentiate between normal
      (non-malignant) and cancerous cells based on their physico-chemical properties.
      This is relatively simple when studied cancerous cells originate from distant
      stages of cancer progression. Here, studies on chemical properties of two closely
      related human melanoma cell lines are presented: WM115 melanoma cells were taken
      from the vertical growth phase while WM266-4 from the skin metastatic site of the
      same patient. Their chemical properties were studied by two techniques, namely
      time-of-flight secondary ion mass spectra (ToF SIMS) and photothermal
      microspectroscopy (PTMS), used to record mass and photothermal spectra of cells,
      respectively. In our approach, independently of the spectra type, its full range,
      i.e. masses and wavenumbers within the range 0-500 kDa and 500-4000 cm-1,
      underwent a similar methodology for principal component analysis (PCA). PCA
      outcome shows results groupped depending on the sample type (either WM115 or
      WM266-4 cells). The results are independent of the method applied to study
      chemical properties of melanoma cells, indicating that cancer-related changes are
      large enough to be identified with these techniques and to differentiate between
      cells originating from vertical growth phase and skin metastatis.

PMID- 27704078
TI  - Closed bipolar electrode-enabled dual-cell electrochromic detectors for chemical
      sensing.
AB  - Bipolar electrodes (BPE) are electrically floating metallic elements placed in
      electrified fluids that enable the coupling of anodic and cathodic redox
      reactions at the opposite ends by electron transfer through the electrode. One
      particularly compelling application allows electron transfer reactions at one end
      of a closed BPE to be read out optically by inducing a redox-initiated change in
      the optical response function of a reporter system at the other end. Here, a BPE
      enabled method for electrochemical sensing based on the electrochromic response
      of a methyl viologen (MV) reporter is developed, characterized, and rendered in a
      field-deployable format. BPE-enabled devices based on two thin-layer-cells of ITO
      and Pt were fabricated to couple an analytical reaction in one cell with an MV
      reporter reaction, producing a color change in the complementary cell. Using
      Fe(CN)63/4- as a model analyte, the electrochemically induced color change of MV
      was determined initially by measuring its absorbance via a CCD camera coupled to
      a microscope. Then, smartphone-based detection and RGB analysis were employed to
      further simplify the sensing scheme. Both methods produced a linear relationship
      between the analyte concentration, the quantity of MV generated, and the
      colorimetric response, yielding a limit of detection of 1.0 MUM. Similar
      responses were observed in the detection of dopamine and acetaminophen. Further
      evolution of the device replaced the potentiostat with batteries to control
      potential, demonstrating the simplicity and portability of the device. Finally,
      the physical separation of the reporter and analytical cells renders the device
      competent to detect analytes in different (e.g. non-aqueous) phases, as
      demonstrated by using the electrochromic behavior of aqueous MV to detect
      ferrocene in acetonitrile in the analytical cell.

PMID- 27704079
TI  - Evaluation of a nitrogen-incorporated tetrahedral amorphous carbon thin film for
      the detection of tryptophan and tyrosine using flow injection analysis with
      amperometric detection.
AB  - We report on the analytical performance of a tetrahedral amorphous carbon (ta
      C:N) thin-film electrode in flow injection analysis with amperometric detection.
      Two model redox analytes were used to evaluate the electrode response because of
      their positive detection potentials and propensity (i.e., reaction products) to
      adsorb and foul sp2 carbon electrodes: tyrosine and tryptophan. ta-C:N electrodes
      are attractive for electroanalytical applications because they possesses many of
      the excellent properties of boron-doped nanocrystalline diamond (BDD) and they
      can be deposited at or near room temperature. The results show that the ta-C:N
      electrode exhibits lower background current and noise than glassy carbon (GC).
      The electrode was stable microstructurally at the positive potentials used for
      detection, ~1.1 V, of these two amino acids and it exhibited superior analytical
      detection figures of merit as compared to GC and as good or superior to BDD. The
      linear dynamic range for both analytes at ta-C:N was from 0.1 to 100 MUmol L-1,
      the sensitivity was 8-12 mA L mol-1, the short-term response variability was 1
      2%, and the minimum detectable concentration was 89.7 +/- 0.9 nM (18.3 MUg L-1 or
      0.46 ng) for tryptophan and 120 +/- 11 nM (21.7 MUg L-1 or 0.54 ng) for tyrosine.
      The analytical detection figures of merit for these amino acids at GC and BDD are
      also presented for comparison as is characterization data for the chemical
      composition and microstructure of the ta-C:N film.

PMID- 27704080
TI  - A compact imaging spectroscopic system for biomolecular detections on plasmonic
      chips.
AB  - In this study, we demonstrate a compact imaging spectroscopic system for high
      throughput detection of biomolecular interactions on plasmonic chips, based on a
      curved grating as the key element of light diffraction and light focusing. Both
      the curved grating and the plasmonic chips are fabricated on flexible plastic
      substrates using a gas-assisted thermal-embossing method. A fiber-coupled
      broadband light source and a camera are included in the system. Spectral
      resolution within 1 nm is achieved in sensing environmental index solutions and
      protein bindings. The detected sensitivities of the plasmonic chip are comparable
      with a commercial spectrometer. An extra one-dimensional scanning stage enables
      high-throughput detection of protein binding on a designed plasmonic chip
      consisting of several nanoslit arrays with different periods. The detected
      resonance wavelengths match well with the grating equation under an air
      environment. Wavelength shifts between 1 and 9 nm are detected for antigens of
      various concentrations binding with antibodies. A simple, mass-productive and
      cost-effective method has been demonstrated on the imaging spectroscopic system
      for real-time, label-free, highly sensitive and high-throughput screening of
      biomolecular interactions.

PMID- 27704081
TI  - Selective recognition and imaging of bacterial model membranes over mammalian
      ones by using cationic conjugated polyelectrolytes.
AB  - The development of new tools for the detection and fluorescence imaging of
      bacteria is of great interest in clinical diagnosis and food and environmental
      safety. In this work, we have explored the ability of two cationic fluorene-based
      conjugated polyelectrolytes, HTMA-PFP and HTMA-PFNT, emitting in the blue and red
      spectral regions respectively, to selectively label bacterial over mammalian
      cells. With this end in view, vesicles with lipid compositions mimicking those of
      bacterial or mammalian membranes were used as model membranes to explore the
      interaction of the polyelectrolytes with both systems in samples containing
      either a single type of vesicle or a mixture of both. Changes in the intrinsic
      fluorescence of HTMA-PFP and HTMA-PFNT were used to quantify the affinity of
      these polyelectrolytes for the model lipid membranes, while quenching experiments
      were employed to evaluate their selectivity to each lipid system. In addition,
      fluorescence microscopy experiments were performed to check the ability of
      polyelectrolytes to label the vesicles without affecting their integrity. Results
      showed that both polyelectrolytes rapidly label the model vesicles but they
      preferentially bind to those mimicking bacterial membranes, HTMA-PFNT being much
      more selective to this type of membranes than HTMA-PFP. Preliminary experiments
      with living bacteria and mammalian cells support this conclusion, showing that in
      samples with both types of cells together, HTMA-PFNT only images the bacterial
      cells, thus evidencing its potential use for the selective recognition and
      imaging of bacterial presence.

PMID- 27704082
TI  - Evaluation of drug-mediated arrhythmic changes in spontaneous beating
      cardiomyocytes by AFM.
AB  - Arrhythmia caused by drug-induced cardiotoxicity is among the leading reasons for
      late-stage drug attrition and is therefore a core subject in safety testing of
      new compounds. Alternative methods such as surface and interface characterization
      approaches for assessing the drug-mediated cardiotoxicity should be promoted, in
      order to reduce, refine and replace the use of laboratory animals. Here, we
      investigate the possibility of using known human Ether-a-go-go-Related Gene
      (hERG) channel blockers to induce irregular beating patterns in the mouse and
      human induced pluripotent stem cell-derived (miPSC and hiPSC) cardiomyocyte (CM)
      model systems. An AFM-based approach was developed to precisely monitor the
      beating interval and rate of cardiomyocytes. Verification was implemented using
      three individual cardiovascular compounds to validate the potential application
      of this AFM approach as a complementary drug screening tool. Consistent with
      previous reports, isoproterenol increased the beating rate, with a more
      pronounced effect in the mouse CMs, nifedipine increased the beating rate in a
      dose-dependent manner, and sotalol induced arrhythmias with a significant
      variation in beating interval responses at increasing concentrations. The results
      of this initial study show that accurate analysis of individual drug-mediated
      effects can be achieved using our method, comparable to previous reports, and
      that a well-controlled AFM test of ion channel manipulation on human and murine
      derived cardiomyocytes can be performed for investigation on multi-compound
      effects. Preliminary results indicate that the hERG blocker E-4031 can stimulate
      irregular, arrhythmic beating patterns in the cardiomyocytes from both species,
      and that immediate subsequent treatment with the hERG enhancer nicorandil can
      rescue these back to regular beating patterns, similar to those observed when the
      cells were untreated. This approach has not been extensively reported, and the
      use of our AFM system provides a platform to further investigate compound-induced
      ion channel effects in cardiomyocytes for potential application in pre-screening
      drug development stages.

PMID- 27704083
TI  - Fiber enhanced Raman spectroscopic analysis as a novel method for diagnosis and
      monitoring of diseases related to hyperbilirubinemia and hyperbiliverdinemia.
AB  - Fiber enhanced resonance Raman spectroscopy (FERS) is introduced for chemically
      selective and ultrasensitive analysis of the biomolecules hematin, hemoglobin,
      biliverdin, and bilirubin. The abilities for analyzing whole intact, oxygenated
      erythrocytes are proven, demonstrating the potential for the diagnosis of red
      blood cell related diseases, such as different types of anemia and hemolytic
      disorders. The optical fiber enables an efficient light-guiding within a
      miniaturized sample volume of only a few micro-liters and provides a tremendously
      improved analytical sensitivity (LODs of 0.5 MUM for bilirubin and 0.13 MUM for
      biliverdin with proposed improvements down to the pico-molar range). FERS is a
      less invasive method than the standard ones and could be a new analytical method
      for monitoring neonatal jaundice, allowing a precise control of the unconjugated
      serum bilirubin levels, and therefore, providing a better prognosis for newborns.
      The potential for sensing very low concentrations of the bile pigments may also
      open up new opportunities for cancer research. The abilities of FERS as a
      diagnostic tool are explored for the elucidation of jaundice with different
      etiologies including the rare, not yet well understood diseases manifested in
      green jaundice. This is demonstrated by quantifying clinically relevant
      concentrations of bilirubin and biliverdin simultaneously in the micro-molar
      range: for the case of hyperbilirubinemia due to malignancy, infectious
      hepatitis, cirrhosis or stenosis of the common bile duct (1 MUM biliverdin
      together with 50 MUM bilirubin) and for hyperbiliverdinemia (25 MUM biliverdin
      and 75 MUM bilirubin). FERS has high potential as an ultrasensitive analytical
      technique for a wide range of biomolecules and in various life-science
      applications.

PMID- 27704085
TI  - Optical disc technology-enabled analytical devices: from hardware modification to
      digitized molecular detection.
AB  - Beyond their essential applications in portable data storage for the past 30
      years, optical discs and corresponding recording/reading technologies have been
      extensively explored with the ultimate goal of creating novel analytical tools
      for on-site chemical analysis and point-of-care (POC) medical diagnosis. In
      particular, the disc media (CD, DVD, and BD) are proven to be inexpensive and
      versatile substrate materials for the preparation of various biochips and
      microfluidic systems; conventional computer drives and disc players are widely
      adapted for biochip signal reading and microscopic imaging. Herein we provide an
      overview of such optical disc technology-enabled analytical devices, e.g.,
      integrated systems developed from specifically fabricated analog disks, modified
      optical drives, or adapted software algorithms.

PMID- 27704084
TI  - Forster resonance energy transfer to impart signal-on and -off capabilities in a
      single microRNA biosensor.
AB  - Many studies have found that over- or under-expression of biomolecules called
      microRNAs (miRNA) regulates several diseases. Biosensors are in need to visually
      identify the relative expression level of miRNA to determine the direction these
      miRNA change in cells and tissues. Our established reporter+probe miRNA biosensor
      design requires that miRNA outcompete and displace the reporter from the probe.
      Once displaced, the reporter folds into a hairpin structure to force together a
      pair of Forster Resonance Energy Transfer (FRET) dyes. The donor and acceptor
      signal changes can be used to indicate the over-/under-expression of miRNA. The
      bright signal from the donor will indicate miRNA under-expression; the bright
      acceptor signal will indicate miRNA over-expression. Since close proximity of the
      dyes to each other and nucleic acids often quench fluorescence, polyethylene
      glycol spacers were added in-between the dyes and nucleic acids. We compared
      reporter designs with and without spacers to investigate the effects on the
      following analytical metrics: (1) extent of signal change, (2) limits of
      detection and quantitation, and (3) sensitivity. Systematic errors and amount of
      reporter+probe biosensor formed were evaluated for one of the biosensors. Cy3|Cy5
      and 6-carboxyfluorescein (6-FAM)|ATTO 633 dye pairs on reporters containing
      spacers showed an increase in the acceptor signal change by ~190 and ~484%,
      respectively, compared to no spacers. Transduction mechanisms that enhance and
      quench the signal both showed LODs that ranged from 3-17 nanomolar (nM) with 100
      nM of the biosensor.

PMID- 27704086
TI  - Comparison of the specificity and affinity of surface immobilised Affimer binders
      using the quartz crystal microbalance.
AB  - To enable multiplexed protein analysis through the use of microarrays, reliable
      molecules capable of specifically binding to a protein of interest with high
      affinity are required. Further, this specificity and affinity must be retained
      upon immobilization to the microarray surface. This study investigates the
      performance of surface bound Affimer proteins, comparing the affinity and
      specificity of different binders for closely related immunoglobulin molecules
      using the quartz crystal microbalance with dissipation monitoring (QCM-D). It is
      demonstrated that the surface bound Affimer proteins are highly specific,
      differentiating between their target IgG and other closely related IgG
      subclasses. The binding affinities of the protein aptamers for their target IgG
      molecules are determined to be in the nanomolar range, comparable to typical
      antibody-antigen binding affinities. While measurements herein are done using QCM
      D, the high specificity and binding affinities of the surface bound Affimer
      proteins opens applications in a range of microarray biosensors.

PMID- 27704087
TI  - Effect of lithographically designed structures on the caffeine sensing properties
      of surface imprinted films.
AB  - In this study, molecularly imprinted films with concave and convex hemispherical
      patterns were fabricated using soft lithography and photopolymerization, and
      their dynamic sensing properties were compared using the gravimetric detection of
      caffeine.

PMID- 27704088
TI  - Fourier transform infrared spectroscopy on external perturbations inducing
      secondary structure changes of hemoglobin.
AB  - The secondary structure of proteins and their conformation are intimately related
      to their biological functions. In this study, heat-induced changes in the
      secondary structure and conformation of hemoglobin were investigated via infrared
      attenuated total reflection (IR-ATR) spectroscopy. The secondary structure
      changes of hemoglobin were derived from IR-ATR spectra using second derivatives
      and curve fitting. Thereby, the thermal denaturation temperature ranges and the
      secondary structure changes with temperature were revealed. More detailed
      information on the secondary structure and conformation was elucidated via two
      dimensional infrared correlation spectroscopy. This study deciphers the detailed
      conformational behavior of hemoglobin molecular changes along with temperature,
      and creates a general methodological framework for analyzing the heat-induced
      behavior of biomacromolecules.

PMID- 27704089
TI  - Microchip in situ electrosynthesis of silver metallic oxide clusters for ultra
      FAST detection of galactose in galactosemic newborns' urine samples.
AB  - This work describes for the first time the coupling of microfluidic chips (MC) to
      electrosynthetized silver metallic oxide clusters (AgMOCs). As an early
      demonstration of this novel approach, the ultrafast detection of galactose in
      galactosemic newborns' urine samples is proposed. AgMOCs were in situ
      electrosynthetized on integrated microchip platinum electrodes using a double
      pulse technique and characterized in full using scanning electronic microscopy
      (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron
      spectroscopy (XPS) and electrochemical techniques revealing the presence of
      silver oxides and electrocatalysis towards galactose as a galactosemia biomarker.
      Galactose detection in galactosemic newborns' urine samples proceeded in less
      than 30 s, differentiating between ill and healthy urine samples and requiring
      negligible urine sample consumption. The significance of the newborns' urine
      samples confirmed the analytical potency of the MC-AgMOCs approach for future
      implementation of screening for rare disease diagnosis such as galactosemia.

PMID- 27704090
TI  - Synthesis and characterization of DNA-quantum dot conjugates for the fluorescence
      ratiometric detection of unlabelled DNA.
AB  - A quantum dot-based ratiometrically responsive fluorescent sensor for unlabeled
      single-stranded DNA (ssDNA) is reported. Several technical issues concerning the
      development of high yield ssDNA-QD conjugation chemistry were addressed. The DNA
      sensor was synthesized by conjugating methacrylic phosphoramidite-functional
      oligonucleotides to water-soluble cadmium zinc sulfide core/zinc sulfide shell
      quantum dots (CdZnS/ZnS QDs). Duplex DNA was formed when the QD-bound ssDNA was
      incubated with its complement. Next, titration with PicoGreen resulted in FRET
      energy transfer from the dot to the dsDNA intercalating dye. The resulting ratio
      of the dye to QD integrated emissions is a calibratable metric for label-free DNA
      detection with a LOD of 3.8 nmol.

PMID- 27704091
TI  - Online coupling techniques in ambient mass spectrometry.
AB  - Since ambient mass spectrometry (AMS) has been proven to have low matrix effects
      and high salt tolerance, great efforts have been made for online coupling of
      several analytical techniques with AMS. These analytical techniques include gas
      chromatography (GC), liquid chromatography (LC), capillary electrophoresis (CE),
      surface plasmon resonance (SPR), and electrochemistry flow cells. Various ambient
      ionization sources, represented by desorption electrospray ionization (DESI) and
      direct analysis in real time (DART), have been utilized as interfaces for the
      online coupling techniques. Herein, we summarized the advances in these online
      coupling methods. Close attention has been paid to different interface setups for
      coupling, as well as limits of detection, tolerance to different matrices, and
      applications of these new coupling techniques.

PMID- 27704092
TI  - Towards DNA methylation detection using biosensors.
AB  - DNA methylation, a stable and heritable covalent modification which mostly occurs
      in the context of a CpG dinucleotide, has great potential as a biomarker to
      detect disease, provide prognoses and predict therapeutic responses. It can be
      detected in a quantitative manner by many different approaches both genome-wide
      and at specific gene loci, in various biological fluids such as urine, plasma,
      and serum, which can be obtained without invasive procedures. The current,
      classical methods are effective in studying DNA methylation patterns, however,
      for the most part; they have major drawbacks such as expensive instruments,
      complicated and time consuming protocols as well as relatively low sensitivity,
      and high false positive rates. To overcome these obstacles, great efforts have
      been made toward the development of reliable sensor devices to solve these
      limitations, providing sensitive, fast and cost-effective measurements. The use
      of biosensors for DNA methylation biomarkers has increased in recent years,
      because they are portable, simple, rapid, and inexpensive which offers a
      straightforward way to detect methylated biomarkers. In this review, we give an
      overview of the conventional techniques for the detection of DNA methylation and
      then will focus on recent advances in biosensor based methylation detection that
      eliminate bisulfite conversion and PCR amplification.

PMID- 27704093
TI  - Smart sensory materials for divalent cations: a dithizone immobilized membrane
      for optical analysis.
AB  - An optode for Cu(ii), Cd(ii), Zn(ii) and Hg(ii) sensing has been designed by
      immobilization of dithizone on a triacetylcellulose membrane (mem-DTZ). The
      sorption of the metal ions on the mem-DTZ has been thoroughly characterized, in
      particular sorption kinetics, sorption isotherms and profiles as a function of
      the pH have been studied. Methods to assess the concentrations of the cations,
      both individually and in a mixture, in unknown samples, have been developed. In
      particular, UV-vis spectra and digital information of pictures taken by using a
      common desktop scanner, of the mem-DTZ sensor after equilibration with different
      solutions, were acquired and they were correlated with the concentration of the
      metal ions in solutions. For the single analyte determination, the RGB parameters
      of the pictures were subjected to Principal Component Analysis (PCA); otherwise
      the UV-vis spectra of a mixture of two cations were elaborated by Partial Least
      Squares (PLS) Regression. The membrane responds to the divalent cations by
      changing colour reversibly. The response time of the mem-DTZ is about 1 h for
      Cd(ii), Hg(ii) and Zn(ii), but longer for Cu(ii): more than 10 h are required.
      The linear interval is in the range of about 10-7 to 10-5 M for all metal ions.
      The limit of detection (LOD) is around 10-6 M for Cu(ii), Cd(ii) and Hg(ii); for
      Zn(ii) a lower LOD of 10-7 M is obtained. The applicability of mem-DTZ to real
      samples has been proved by analysis of the four metal cations in a certificate
      material (Sewage Sludge CC136A), white wine, and drinking water samples.

PMID- 27704094
TI  - Correction: Measuring the effects of fractionated radiation therapy in a 3D
      prostate cancer model system using SERS nanosensors.
AB  - Correction for 'Measuring the effects of fractionated radiation therapy in a 3D
      prostate cancer model system using SERS nanosensors' by Victoria L. Camus, et
      al., Analyst, 2016, 141, 5056-5061.

PMID- 27704095
TI  - Correction: Resonance Raman spectroscopy as an in situ probe for monitoring
      catalytic events in a Ru-porphyrin mediated amination reaction.
AB  - Correction for 'Resonance Raman spectroscopy as an in situ probe for monitoring
      catalytic events in a Ru-porphyrin mediated amination reaction' by Paolo Zardi et
      al., Analyst, 2016, 141, 3050-3058.

PMID- 27704096
TI  - Infrared spectroscopy via substrate-integrated hollow waveguides: a powerful tool
      in catalysis research.
AB  - Substrate-integrated hollow waveguides (iHWG) represent an innovative generation
      of photon conduits, which can simultaneously serve as highly miniaturized gas
      cells with low sample volume. In this communication, we introduce a novel concept
      for analyzing the performance of catalysts via infrared gas phase analysis based
      on iHWGs. Due to rapid gas exchange and sample transient times within the iHWG,
      compositional changes of a continuous gas stream after interaction with a
      catalyst assembly can be monitored with high time resolution.

PMID- 27704097
TI  - Correction: Evaluation of a nitrogen-incorporated tetrahedral amorphous carbon
      thin film for the detection of tryptophan and tyrosine using flow injection
      analysis with amperometric detection.
AB  - Correction for 'Evaluation of a nitrogen-incorporated tetrahedral amorphous
      carbon thin film for the detection of tryptophan and tyrosine using flow
      injection analysis with amperometric detection' by Romana Jarosova, et al.,
      Analyst, 2016, DOI: .

PMID- 27704098
TI  - Sildenafil (Viagra) A breakthrough in the management of an old problem or a risky
      drug.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704099
TI  - Status of long term care in Saudi Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704100
TI  - The centrality of the patient role in the management of insulin dependent
      diabetes mellitus.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704101
TI  - Why treat dyslipidemia?
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704102
TI  - Surgery for spontaneous intracerebral hematoma.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704103
TI  - Cost estimation and physicians' awareness concerning hypertension management:
      Experience from primary care centres.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704104
TI  - Birthweight-specific neonatal mortalities.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704105
TI  - Does nonperforated appendicitis need antibiotic cover in children?
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704106
TI  - Laparoscopic appendicectomy.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704108
TI  - Comparison of inhaled nebulised adrenaline with salbutamol in acute asthma.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704107
TI  - Cholelithiasis in infancy and childhood.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704109
TI  - Incidence of salmonella infection among neonates in a pediatric hospital.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704110
TI  - Microbiology and antimicrobials sensitivity of supprative otitis media.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704111
TI  - Accidental poisoning in children.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704112
TI  - Air gun injuries in children.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704114
TI  - Breastfeeding: Knowledge and attitude of college girls.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704113
TI  - Pattern of childhood meningitis in Oman.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704115
TI  - Are health workers adequately trained to manage and promote breastfeeding?
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704116
TI  - Clinical biochemical and therapeutic aspects of diabetic ketoacidosis and its
      outcome.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704117
TI  - Lipid peroxidation in the erythrocytes of the obese diabetic subjects.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704118
TI  - Screening for gestational diabetes.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704119
TI  - Risk factors for coronary artery disease in newly diagnosed non insulin dependent
      diabetes mellitus: Prevalence in Bahraini compared with Asian Indian patients.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704120
TI  - Prevalence of diabetes mellitus and hypertension in relation to chemical
      composition of drinking water: Does magnesium protect against diabetes mellitus?
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704121
TI  - Influence of concomitant medical diseases on the course of bleeding duodenal
      ulcers.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704122
TI  - Chemoembolization in hepatocellular carcinoma.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704123
TI  - Evaluation of an immunoluminometric based assay as a novel method for the
      quantitative analysis of p53 protein in tumor tissues.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704125
TI  - Low back pain among Saudi school workers in Jeddah.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704124
TI  - Oral pathosis and trigeminal neuralgia: A clinical study.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704126
TI  - Cytophagic histiocytic panniculitis with T-Cell proliferation.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704127
TI  - Non puerperal inversion of the uterus in a teenager.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704128
TI  - Hydrocolpos: The spectrum.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704130
TI  - Ceftriaxone treatment failure of meningitis due to penicillin and ceftriaxone
      resistant streptococcus pneumonia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704129
TI  - Isolated Langerhans' cell histiocytosis of the spine: A diagnostic and
      therapeutic challenge.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704131
TI  - Uncommon metastases of bronchopulmonary neuroendocrine tumors.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704132
TI  - Vogt-Koyanagi-Harada Syndrome as a case of aseptic meningitis in Children.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704134
TI  - Bowel preparation for Barium Enema with Picosalax Sachets. (A simplified method).
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704133
TI  - Amoebama of the Caecum associated with Hepatic Amoebic Abscess.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704135
TI  - Methicillin resistant Catalase Negative Staphylococcus aureus.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704136
TI  - Sickle cell gene as a multifaceted problem in Saudi Arabia.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704137
TI  - Challenges and dilemmas facing medical education, practice and research in a
      world of changing paradigms and unequal resources.
AB  - Full text is available as a scanned copy of the original print version.

PMID- 27704138
TI  - Toward Designing Information Display to Support Critical Care. A Qualitative
      Contextual Evaluation and Visioning Effort.
AB  - OBJECTIVES: Electronic health information overload makes it difficult for
      providers to quickly find and interpret information to support care decisions.
      The purpose of this study was to better understand how clinicians use information
      in critical care to support the design of improved presentation of electronic
      health information. METHODS: We conducted a contextual analysis and visioning
      project. We used an eye-tracker to record 20 clinicians' information use
      activities in critical care settings. We played video recordings back to
      clinicians in retrospective cued interviews and queried: 1) context and goals of
      information use, 2) impacts of current display design on use, and 3) processes
      related to information use. We analyzed interview transcripts using grounded
      theory-based content analysis techniques and identified emerging themes. From
      these, we conducted a visioning activity with a team of subject matter experts
      and identified key areas for focus of design and research for future display
      designs. RESULTS: Analyses revealed four unique critical care information use
      activities including new patient assessment, known patient status review,
      specific directed information seeking, and review and prioritization of multiple
      patients. Emerging themes were primarily related to a need for better
      representation of dynamic data such as vital signs and laboratory results,
      usability issues associated with reducing cognitive load and supporting efficient
      interaction, and processes for managing information. Visions for the future
      included designs that: 1) provide rapid access to new information, 2) organize by
      systems or problems as well as by current versus historical patient data, and 3)
      apply intelligence toward detecting and representing change and urgency.
      CONCLUSIONS: The results from this study can be used to guide the design of
      future acute care electronic health information display. Additional research and
      collaboration is needed to refine and implement intelligent graphical user
      interfaces to improve clinical information organization and prioritization to
      support care decisions.

PMID- 27704140
TI  - RhoA/ROCK signaling regulates TGFbeta-induced epithelial-mesenchymal transition
      of lens epithelial cells through MRTF-A.
AB  - Transforming growth factor (TGF)-beta-induced epithelial-mesenchymal transition
      (EMT) leads to the formation of ocular fibrotic pathologies, such as anterior
      subcapsular cataract and posterior capsule opacification. Remodeling of the actin
      cytoskeleton, mediated by the Rho family of GTPases, plays a key role in EMT,
      however, how actin dynamics affect downstream markers of EMT has not been fully
      determined. Our previous work suggests that myocardin related transcription
      factor A (MRTF-A), an actin-binding protein, might be an important mediator of
      TGFbeta-induced EMT in lens epithelial cells. The aim of the current study was to
      determine the requirement of RhoA/ROCK signaling in mediating TGFbeta-induced
      nuclear accumulation of MRTF-A, and ultimate expression of alpha-smooth muscle
      actin (alphaSMA), a marker of a contractile, myofibroblast phenotype. Using rat
      lens epithelial explants, we demonstrate that ROCK inhibition using Y-27632
      prevents TGFbeta-induced nuclear accumulation of MRTF-A, E-cadherin/beta-catenin
      complex disassembly, and alphaSMA expression. Using a novel inhibitor
      specifically targeting MRTF-A signaling, CCG-203971, we further demonstrate the
      requirement of MRTF-A nuclear localization and activity in the induction of
      alphaSMA expression. Overall, our findings suggest that TGFbeta-induced
      cytoskeletal reorganization through RhoA/ROCK/MRTF-A signaling is critical to EMT
      of lens epithelial cells.

PMID- 27704142
TI  - HIV-1 infection, microenvironment and endothelial cell dysfunction.
AB  - HIV-1 promotes a generalized immune activation that involves the main targets of
      HIV-1 infection but also cells that are not sensitive to viral infection. ECs
      display major dysfunctions in HIV+ patients during long-standing viral infection
      that persist even in the current cART era, in which new-generation drugs have
      reduced dysmetabolic side effects and successfully impeded viral replication. In
      vivo studies have failed to demonstrate the presence of replicating virus in ECs
      suggesting that a direct role of the virus is unlikely, and implying that the
      mechanism accounting for vascular dysfunction may rely on the indirect action of
      molecules released in the microenvironment by HIV-1-infected cells. This article
      reviews the current understanding of how HIV-1 infection can contribute to
      vascular dysfunction. In particular, we discuss the emerging role played by
      different HIV-1 proteins in driving inflammation and EC dysregulation, and
      highlight the need to target them for therapeutic benefit.

PMID- 27704141
TI  - Toward laboratory blood test-comparable photometric assessments for anemia in
      veterinary hematology.
AB  - Anemia associated with intestinal parasites and malnutrition is the leading cause
      of morbidity and mortality in small ruminants worldwide. Qualitative scoring of
      conjunctival redness has been developed so that farmers can gauge anemia in sheep
      and goats to identify animals that require treatment. For clinically relevant
      anemia diagnosis, complete blood count-comparable quantitative methods often rely
      on complicated and expensive optical instruments, requiring detailed spectral
      information of hemoglobin. We report experimental and numerical results for
      simple, yet reliable, noninvasive hemoglobin detection that can be correlated
      with laboratory-based blood hemoglobin testing for anemia diagnosis. In our pilot
      animal study using calves, we exploit the third eyelid (i.e., palpebral
      conjunctiva) as an effective sensing site. To further test spectrometer-free (or
      spectrometerless) hemoglobin assessments, we implement full spectral
      reconstruction from RGB data and partial least square regression. The unique
      combination of RGB-based spectral reconstruction and partial least square
      regression could potentially offer uncomplicated instrumentation and avoid the
      use of a spectrometer, which is vital for realizing a compact and inexpensive
      hematology device for quantitative anemia detection in the farm field.

PMID- 27704139
TI  - Pigmy MicroRNA: surveillance cops in Therapies kingdom.
AB  - MicroRNAs (miRNAs) are well preserved in every animal. These pigmy sized non
      coding RNAs (21-23 nt), scattered in genome, are responsible for micromanaging
      the versatile gene regulations. Involvement of miRNAs was surveillance cops in
      all human diseases including cardiovascular defects, tumor formation,
      reproductive pathways, and neurological and autoimmune disorders. The effective
      functional role of miRNA can be reduced by chemical entities of antisense
      oligonucleotides and versatile small molecules that support the views of novel
      therapy of different human diseases. In this study, we have updated our current
      understanding for designing and synthesizing miRNA-controlling therapeutic
      chemicals. We have also proposed various in-vivo delivery strategies and their
      ongoing challenges to combat the incorporation hurdles in live cells and animals.
      Lastly, we have demonstrated the current progress of miRNA modulation in the
      treatment of different human diseases that provides an alternative approach of
      gene therapy.

PMID- 27704143
TI  - 48 week outcomes of maraviroc-containing regimens following the genotypic or
      Trofile assay in HIV-1 failing subjects: the OSCAR Study.
AB  - This study assessed the 48-week efficacy of an antiretroviral therapy including
      maraviroc following the assessment of co-receptor tropism by use of Geno2Pheno
      algorithm or the Trofile phenotypic assay in failing treatment-experienced HIV-1
      patients. This was a multicenter, randomized, open-label, non-inferiority trial.
      Treatment-experienced subjects with HIV-RNA >=500 copies/mL were randomized (1:1)
      to undergo co-receptor tropism testing by the Geno- 2Pheno algorithm (with a
      false positive rate >10%) or the Trofile assay before starting a new
      antiretroviral treatment which included maraviroc. The primary endpoint was the
      48 week proportion of patients with treatment success (TS). Intention-to-treat
      analyses are also reported. One hundred and fifty-five experienced patients were
      analysed: 77 patients in the Trofile arm and 78 in the Genotype arm. The 48-week
      proportion of TS was 87% in the Trofile arm and 89% in the Genotype arm
      (difference: 1.5%, 95%CI: -8.9% to 11.8%) suggesting non-inferiority. In the
      Trofile arm, 10 patients had treatment failure: 5 viral rebound, 5
      discontinuations. In the Genotype arm, 9 patients had treatment failure: 7 viral
      rebound, 2 lost to follow-up. CD4+ significantly increased from baseline to week
      48 in both arms. 48-week treatment success was similar for maraviroc-including
      therapy prescribed following the Trofile phenotypic assay or Geno2Pheno
      algorithm.

PMID- 27704144
TI  - Bacterial agents as a cause of infertility in humans.
AB  - Infertility is a problem affecting almost 15% of couples. There are many causes
      for this condition, among which urogenital bacterial infections seem to play an
      important role. Many studies have explained the mechanisms by which bacteria
      cause infertility both in men and women. Therefore we undertook this study to
      evaluate the presence of genito-urinary infections in infertile couples who
      sought counselling to investigate their condition. Microbiological analysis was
      performed on semen and vaginal/cervical samples of both partners of each couple.
      The percentage of individuals affected by a urogenital bacterial infection was
      between 14 and 20%. More significantly, most of the species isolated both in men
      and women have been described in the literature as potential causes of
      infertility.

PMID- 27704145
TI  - Transcriptional activity of human endogenous retrovirus in Albanian children with
      autism spectrum disorders.
AB  - Recent studies suggest that autism spectrum disorders (ASD) result from
      interactions between genetic and environmental factors, whose possible links
      could be represented by epigenetic mechanisms. Here, we investigated the
      transcriptional activity of three human endogenous retrovirus (HERV) families, in
      peripheral blood mononuclear cells (PBMCs) from Albanian ASD children, by
      quantitative real-time PCR. We aimed to confirm the different expression profile
      already found in Italian ASD children, and to highlight any social and family
      health condition emerging from information gathered through a questionnaire, to
      be included among environmental risk factors. The presence of increased HERV-H
      transcriptional activity in all autistic patients could be understood as a
      constant epigenetic imprinting of the disease, potentially useful for early
      diagnosis and for the development of effective novel therapeutic strategies.

PMID- 27704146
TI  - First evidence of HERV-H transcriptional activity reduction after methylphenidate
      treatment in a young boy with ADHD.
AB  - Human endogenous retroviruses (HERVs) have been associated with many complex
      diseases including neuropsychiatric diseases, such as attention deficit
      hyperactivity disorder (ADHD). In ADHD an over-expression of HERV-H family in
      peripheral blood mononuclear cells has been documented. It has been hypothesized
      that HERVs may represent the link between genetic and environmental risk factors,
      contributing to the clinical onset and/or to the progression of the
      neurodevelopmental disease. The effect of pharmacological treatment on HERV
      transcriptional activity in psychiatric disorders has been attracting attention.
      Using a real-time RT-PCR we investigated the influence of methylphenidate on HERV
      transcription in peripheral blood mononuclear cells of a young patient with ADHD.
      In this clinical case we describe for the first time the reduction of HERV-H
      expression and the significant improvement of ADHD symptoms after 6 months of
      methylphenidate treatment.

PMID- 27704147
TI  - Impact of hepatobiliary phase liver MRI versus Contrast-Enhanced Ultrasound after
      an inconclusive extracellular gadolinium-based contrast-enhanced MRI for the
      diagnosis of benign hepatocellular tumors.
AB  - PURPOSE: To compare the added values of hepatobiliary phase (HBP) MRI and
      contrast-enhanced ultrasound (CEUS) in addition to inconclusive extracellular
      gadolinium-based contrast-enhanced MRI (CE-MRI) to characterize benign
      hepatocellular tumors (BHT). METHODS: Eighty-three BHT-46 focal nodular
      hyperplasia (FNH) and 37 hepatocellular adenomas (HCA)-with inconclusive CE-MRI
      in 54 patients (43 women and 11 men, mean age 42 years old +/- 14.8) were
      retrospectively analyzed. All patients underwent both HBP-MRI and CEUS. Two
      radiologists independently reviewed 2 sets of images, SET-1: CE-MRI and HBP-MRI;
      SET-2: CE-MRI and CEUS, and classified lesions as "definite FNH," "possible FNH,"
      or "definitely not FNH." Sensitivity (Se) and specificity (Spe) were compared
      between the two sets; subgroup analyses according to the lesion's size were
      performed. RESULTS: Regardless of lesion size, the respective Se and Spe of both
      datasets were not statistically different (95.7 and 100% vs. 76.1 and 94.6% for
      set-1 and -2 respectively; p = 0.18). For lesions larger than 35 mm, although
      both sets had similar specificity (100%), sensitivity was higher for SET-1 (100%
      vs. 40%); p = 0.04. Tumor classifications using SET-1 and SET-2 could have
      changed patient management in 35/54 (64.8%) and 33/54 (61.1%) of all patients,
      respectively. CONCLUSIONS: HBP-MRI or CEUS should be performed after an
      inconclusive CE-MRI. Both can change patient management by avoiding unnecessary
      biopsy or surveillance. The use of HBP-MRI should be advocated over CEUS in
      larger (>35 mm) lesions.

PMID- 27704148
TI  - Fluoroscopy versus sonography for image guidance in peripheral MSK intervention.

PMID- 27704150
TI  - Intensive care medicine in 2050: the future of ICU treatments.

PMID- 27704149
TI  - Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma : New study
      concepts of the German Hodgkin Study Group.
AB  - BACKGROUND: Patients with classical Hodgkin's lymphoma (cHL) have a good
      prognosis even in advanced stages. However, combined chemo- and radiotherapy, as
      the standard of care, is also associated with treatment-related toxicities such
      as organ damage, secondary neoplasias, infertility, or fatigue and long-term
      fatigue. Many patients suffer from this burden although their cHL was cured.
      Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1
      antibodies in the treatment of solid cancers and also in HL offers new options. A
      remarkable and durable response rate with a favorable toxicity profile was
      observed in heavily pretreated cHL patients. METHODS: Planning to perform
      prospective randomized clinical trials in the content of radio-immune treatment
      in patients with Hodgkin's lymphoma (HL), we transferred the results of
      preliminary clinical studies and basic research in clinical relevant study
      concepts. RESULTS: Based on these promising early phase trial data, the German
      Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in
      upcoming phase II trials. CONCLUSION: The therapeutic efficacy and potential
      synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will
      be investigated in various settings of HL.

PMID- 27704151
TI  - What patient data should be collected in this randomized controlled trial in
      sepsis?

PMID- 27704152
TI  - Treatment of severe MRSA infections: current practice and further development.

PMID- 27704153
TI  - In the footsteps of Bonney and Nichols: hysterectomy during surgical repair of
      pelvic organ prolapse.
AB  - Based on the available urogynecological literature, the role of hysterectomy in
      the surgical strategy of pelvic organ prolapse (POP) repair remains
      controversial. Currently, there are no data to favor either the removal or
      preservation of the uterus in women with POP. The findings that hysterectomy may
      contribute to a higher success rate and to the development of urinary
      incontinence and/or female sexual dysfunction are not supported by evidence. It
      is not clear why both hysteropexy was sometimes performed in the presence of
      overt uterine prolapse and/or concomitant vaginal hysterectomy was often included
      in vaginal prolapse repair in the absence of uterine prolapse. In our opinion, it
      makes both anatomical and clinical sense to remove the uterus only (and always)
      when the uterus is one of the pelvic organs directly involved in the prolapse,
      but to preserve and suspend the uterus otherwise.

PMID- 27704154
TI  - Age-related alterations in female obturator internus muscle.
AB  - INTRODUCTION AND HYPOTHESIS: Pelvic floor muscle rehabilitation is a widely
      utilized, but often challenging therapy for pelvic floor disorders, which are
      prevalent in older women. Regimens involving the use of appendicular muscles,
      such as the obturator internus (OI), have been developed for strengthening of the
      levator ani muscle (LAM). However, changes that lead to potential dysfunction of
      these alternative targets in older women are not well known. We hypothesized that
      aging negatively impacts OI architecture, the main determinant of muscle
      function, and intramuscular extracellular matrix (ECM), paralleling age-related
      alterations in LAM. METHODS: OI and LAM were procured from three groups of female
      cadaveric donors (five per group): younger (20 - 40 years), middle-aged (41 - 60
      years), and older (>=60 years). Architectural predictors of the excursional
      (fiber length, L f), force-generating (physiological cross-sectional area, PCSA)
      and sarcomere length (L s) capacity of the muscles, and ECM collagen content
      (measure of fibrosis) were determined using validated methods. The data were
      analyzed using one-way ANOVA and Tukey's post-hoc test with a significance level
      of 0.05, and linear regression. RESULTS: The mean ages of the donors in the three
      groups were 31.2 +/- 2.3 years, 47.6 +/- 1.2 years, and 74.6 +/- 4.2 years (P <
      0.005). The groups did not differ with respect to parity or body mass index (P >
      0.5). OI L f and L s were not affected by aging. Age >60 years was associated
      with a substantial decrease in OI PCSA and increased collagen content (P < 0.05).
      Reductions in OI and LAM force-generating capacities with age were highly
      correlated (r 2 = 0.9). CONCLUSIONS: Our findings of age-related decreases in
      predicted OI force production and fibrosis suggest that these alterations should
      be taken into consideration, when designing pelvic floor fitness programs for
      older women.

PMID- 27704155
TI  - Visuo-oculomotor skills related to the visual demands of sporting environments.
AB  - The aim of this study was to assess the visuo-oculomotor skills of gaze
      orientation in selected sport activities relative to visual demands of the
      sporting environment. Both temporal and spatial demands of the sporting
      environment were investigated: The latency and accuracy of horizontal saccades
      and the gain of the horizontal smooth pursuit of the sporting environment were
      investigated in 16 fencers, 19 tennis players, 12 gymnasts, 9 swimmers and 18
      sedentary participants. For the saccade test, two sequences were tested: In the
      fixed sequence, participants knew in advance the time interval between each
      target, as well as the direction and the amplitude of its reappearance; in the
      Freyss sequence however, the spatial changes of the target (direction and
      amplitude) were known in advance by participants but the time interval between
      each target was unknown. For the smooth-pursuit test, participants were
      instructed to smoothly track a target moving in a predictable sinusoidal,
      horizontal way without corrective ocular saccades, nor via anticipation or head
      movements. The results showed no significant differences between specificities of
      selected sporting activities via the saccade latency (although shorter than in
      non-athletes), contrary to saccade accuracy and the gain of smooth pursuit.
      Higher saccade accuracy was observed overall in fencers compared to non-athletes
      and all other sportsmen with the exception of tennis players. In the smooth
      pursuit task, only tennis players presented a significantly higher gain compared
      to non-athletes and gymnasts. These sport-specific characteristics of the visuo
      oculomotor skills are discussed with regard to the different cognitive skills
      such as attentional allocation and cue utilization ability as well as with regard
      to the difference in motor preparation.

PMID- 27704156
TI  - Oxidative stress and gene expression profiling of cell death pathways in alpha
      cypermethrin-treated SH-SY5Y cells.
AB  - In this study, we investigated the induction of oxidative stress and apoptosis in
      human neuroblastoma cell line SH-SY5Y in response to alpha-cypermethrin (alpha
      CYPER) exposure. MTT and LDH assays were carried out to assess the alpha-CYPER
      cytotoxicity. The IC50 value for alpha-CYPER was calculated to be 78.3 +/- 2.98
      uM for the MTT assay and 71.5 +/- 3.94 uM for LDH assay. The pyrethroid alpha
      CYPER (1-100 uM), in a dose-dependent manner, induced a significant increase in
      lipid peroxides measured as malondialdehyde (MDA) and in the levels of nitric
      oxide (NO). The neuroprotective role of three antioxidants, melatonin (MEL),
      Trolox and N-acetylcysteine (NAC) against alpha-CYPER-induced oxidative stress
      was examined. Compared to other antioxidants, MEL (1 uM) treatment showed the
      most effective protection against alpha-CYPER-induced lipid peroxidation and NO
      production. The effects of alpha-CYPER on gene expression profiling of cell death
      pathway in human neuroblastoma SH-SY5Y cells were also investigated. Of the 84
      genes examined (P < 0.001; fold change >1.5), changes in mRNA levels were
      detected in 39 genes: 36 were up-regulated and 3 were down-regulated. A greater
      fold change reversion than 3.5-fold was observed on the up-regulated ATP6V1G2,
      BCL2, CASP9, FAS, GADD45A, SPATA2, SYCP2, ATG7, NFKB1, SNCA, ULK1 and JPH3 genes.
      The results demonstrated that alpha-CYPER alters the expression of apoptosis-,
      autophagy- and necrosis genes as well as induces oxidative stress which may lead
      to DNA damage. The detailed knowledge of the changes in gene expression obtained
      will provide a basis for further elucidating the molecular mechanisms of the
      alpha-CYPER-induced toxicity.

PMID- 27704157
TI  - Different synovial vasculogenic profiles of primary, rapidly destructive and
      osteonecrosis-induced hip osteoarthritis. An immunohistochemistry study.
AB  - PURPOSE: To present a hypothesis regarding the pathways of angiogenesis in
      primary versus secondary hip osteoarthritis (OA). METHODS: In synovial tissue
      samples provided by 57 consecutive patients who underwent hip arthroplasty,
      immunohistochemical examinations were performed using the following angiogenesis
      related antibodies: VEGF-A, COX-2, maspin and the endothelial cells markers CD31
      and CD105. The cases were divided into three categories: classic primary hip OA
      (group A; n = 16), rapidly destructive hip OA (group B; n = 24) and hip OA
      secondary to avascular osteonecrosis of the femoral head (group C; n = 17). The
      endothelial area (EA) was digitally quantified for both CD31 and CD105. RESULTS:
      The large mature vessels with CD105-positive activated endothelium predominated
      in group C, which also showed the highest CD105 median EA value (7.31 +/- 4.01,
      compared to 4.76 +/- 3.73 for group A and 6.69 +/- 3.53 for group B). In groups A
      and B, synovial cell hyperplasia and the predominance of small immature vessels
      were characteristic. CD105, VEGF-A and COX-2 were focally seen in the synovial
      membrane, without maspin positivity. CONCLUSIONS: The severity of hip OA can be
      related to angiogenesis pathways that are not maspin-mediated. In primary hip OA,
      angiogenesis may be induced by a combined mechanism: hypoxia-related VEGF
      dependent vasculogenesis and endothelial differentiation of the activated
      pluripotent cells, which are released from the hyperplastic synovial cells layer.
      An endothelial mesenchymal transition is assumed to be involved in the fibrotic
      process.

PMID- 27704158
TI  - Influence of pre-operative tear size and tendon retraction on repair outcomes for
      isolated subscapularis tears.
AB  - PURPOSE: The purpose of this study was to investigate the influence of tendon
      tear size, in terms of length and retraction, on clinical and anatomic outcomes
      following repair for isolated subscapularis tears. METHODS: The records of 47
      consecutive repairs of isolated subscapularis lesions were studied to correlate
      pre-operative tear characteristics with clinical and radiographic outcomes.
      RESULTS: Forty patients had complete radiographic outcomes at 3.2 +/- 1.1 years,
      of which 36 had complete clinical outcomes at 3.5 +/- 0.9 years. Re-tears were
      observed in five shoulders (12.5 %). Fatty infiltration increased by one grade in
      20 shoulders (50 %), and by two grades in four shoulders (10 %). Pre-operative
      tear size was associated with the post-operative belly-press test (BPT) (p =
      0.042) and fatty infiltration (p = 0.051). Pre-operative tendon retraction was
      associated with post-operative BPT (p < 0.001) and fatty infiltration (p =
      0.023). CONCLUSIONS: Our results do not entirely prove that prognostic factors
      used for superior and posterior tendon tears apply for the subscapularis. Pre
      operative tendon retraction is a better predictor of outcomes than tear size.
      When tear size and tendon retraction are simultaneously severe, re-tears and poor
      outcomes are more likely.

PMID- 27704159
TI  - Current state of the art in total knee arthroplasty computer navigation.
AB  - PURPOSE: Computer-assisted surgery in orthopaedics is passing through the initial
      adapter phase of technology adoption. It started more than 20 years ago, but the
      uptake of technology is still not widespread. The purpose of this article is to
      introduce the reader to the basic technology and familiarize with the terminology
      used in the computer navigation. METHODS: During this time, the technology has
      matured and we have the evidence to prove its benefits for patients. Not only
      does it help placing the prosthetic components in correct orientation, it also
      helps with other parameters like blood loss and fat embolism reduction. In
      addition to being a teaching and training tool, it has also opened new areas of
      research which now question the traditional practices. Since it is not in
      commonly used, the basic aspects of computer navigation are not very well known.
      RESULTS: This paper outlines some important definitions and restates the
      classification of navigation within the spectrum of computer-assisted
      technologies; it then elaborates on the key principles behind navigation in knee
      arthroplasty and goes through some of the differences between navigation systems.
      Finally, it describes in some detail the surgical steps with an image-free knee
      navigation system. CONCLUSIONS: Computer-assisted navigation is not mainstream
      yet, but this article should help readers unfamiliar with the technology to
      understand the basic terms and how it actually works. LEVEL OF EVIDENCE: III.

PMID- 27704160
TI  - Are stunted young Indonesian children more likely to be overweight, thin, or have
      high blood pressure in adolescence?
AB  - OBJECTIVES: To determine whether stunted young children are at greater risk of
      (1) overweight/obesity or thinness, and (2) high blood pressure (HBP) in
      adolescence. METHODS: A secondary data analysis using the Indonesian Family Life
      Survey waves 1 (1993) to 4 (2007). We generated a 14-year follow-up cohort (1993
      2007) and two 7-year cohorts (1993-2000 and 2000-2007) of children aged 2.0-4.9
      years. Stunting (HAZ < -2), thinness (BMIZ < -2), and overweight/obesity (BMIZ >
      +1) were determined based upon the WHO Child Growth Standards. HBP (>90th
      percentile) was interpreted using the 4th Report on the Diagnosis of HBP in
      Children and Adolescents. RESULTS: 765, 1083, and 1589 children were included in
      the 14-year cohort, and the two 7-year cohort analyses, respectively. In the 7
      year cohorts, early life stunting was inversely associated with
      overweight/obesity (prevalence ratio 0.32 and 0.38, respectively; P < 0.05), but
      no significant association was found with the 14-year cohort. There was no
      significant association between childhood stunting and thinness at adolescence or
      in the odds/likelihood of having high systolic or diastolic blood pressure.
      CONCLUSIONS: We found no association between early life stunting and
      overweight/obesity, thinness and HBP in adolescence.

PMID- 27704162
TI  - TNF-alpha and annexin A2: inflammation in thrombotic primary antiphospholipid
      syndrome.
AB  - Antiphospholipid syndrome (APS) is characterized by thromboses and/or pregnancy
      losses. Laboratory criterion for the diagnosis of APS is the presence of
      antiphospholipid antibodies (anticardiolipin, anti-beta2-glycoprotein I
      (abeta2gpI) and lupus anticoagulant). On the one hand, the latest classification
      criteria for the diagnosis of APS emphasized that thrombotic manifestations of
      the syndrome should be without any signs of an inflammatory process, while on the
      other hand, some recent reports have suggested that APS is a "pro-inflammatory
      state." This article is focused on the importance of TNF-alpha and annexin A2
      (anxA2) for patients with vascular (thrombotic) manifestations of the primary
      APS. The classic antithrombotic and antiplatelet therapy does not protect APS
      patients from the development of recurrent thrombosis. Therefore, an urgent need
      for the introduction of new therapeutic approaches in the treatment of APS
      patients is obvious. This review provides a rationale for the necessity for the
      use of immunomodulatory medications that could interfere with beta2gpI binding to
      its receptor(s), such as anxA2, and/or inhibit TNF-alpha activity.

PMID- 27704161
TI  - Relationship between cigarette smoking and hyperuricemia in middle-aged and
      elderly population: a cross-sectional study.
AB  - The aim of the study was to estimate the cross-sectional association between
      cigarette smoking and the prevalence of hyperuricemia (HU) in the middle-aged and
      elderly males and females. A total of 3415 males and 2932 females were included
      in this study. HU was defined as SUA>= 416 mmol/L for males and >=360 mmol/L for
      females. The smoking status was classified into four categories based on daily
      smoking habit: (1) 0/day; (2) 1-10/day; (3) 11-20/day; and (4) >20/day.
      Multivariable logistic regressions were conducted to examine the aforementioned
      association. The prevalence of HU in the male and female sample was 25.0 and 10.0
      %, respectively. In male subjects, the prevalence of HU in smokers (22.8 %) was
      significantly lower than that in non-smokers (26.5 %) (p = 0.016). Meanwhile,
      with adjustment for potential confounding factors, the prevalence of HU in
      smokers was still lower (OR = 0.83, 95 % CI 0.70-0.98, P = 0.033). Furthermore, a
      significantly inverse association between smoking status and HU was observed in
      the multivariable model. The multivariable-adjusted OR (95 % CI) for HU in the
      second, third and fourth category of smoking status was 0.84 (95 % CI 0.66-1.06),
      0.90 (95 % CI 0.69-1.18) and 0.76 (95 % CI 0.58-0.99), respectively, compared
      with that in the first category. A clear trend (P for trend was 0.036) was
      observed. However, there was no significant association between cigarette smoking
      and HU in female subjects (P for trend was 0.739). This study indicated an
      inverse association between cigarette smoking and the prevalence of HU in the
      middle-aged and elderly male population, independent of some major confounding
      factors. The findings of this study expect further prospective studies to confirm
      the causal relationship.

PMID- 27704163
TI  - Incidental ferumoxytol artifacts in clinical brain MR imaging.
AB  - INTRODUCTION: Ferumoxytol (Feraheme) is a parenteral therapy approved for
      treatment of iron deficiency anemia. The product insert for ferumoxytol states
      that it may affect the diagnostic ability of MRI for up to 3 months. However, the
      expected effects may not be commonly recognized among clinical neuroradiologists.
      Our purpose is to describe the artifacts we have seen at our institution during
      routine clinical practice. METHODS: We reviewed the patients at our institution
      that had brain MRI performed within 90 days of receiving intravenous ferumoxytol.
      The imaging was reviewed for specific findings, including diffusion-weighted
      imaging vascular susceptibility artifact, gradient-echo echo-planar T2*-weighted
      vascular susceptibility artifact, SWI/SWAN vascular susceptibility artifact,
      hypointense vascular signal on T2-weighted images, pre-gadolinium contrast
      vascular enhancement on magnetization-prepared rapid acquisition gradient echo
      (MPRAGE) imaging, and effects on post-gadolinium contrast T1 imaging. RESULTS:
      Multiple artifacts were observed in patients having a brain MRI within 3 days of
      receiving intravenous ferumoxytol. These included susceptibility artifact on DWI,
      GRE, and SWAN/SWI imaging, pre-gadolinium contrast increased vascular signal on
      MPRAGE imaging, and decreased expected enhancement on post-gadolinium contrast T1
      weighted imaging. CONCLUSION: Ferumoxytol can create imaging artifacts which
      complicate clinical interpretation when brain MRI is performed within 3 days of
      administration. Recognition of the constellation of artifacts produced by
      ferumoxytol is important in order to obviate additional unnecessary examinations
      and mitigate errors in interpretation.

PMID- 27704164
TI  - Human multipotent adult progenitor cells enhance islet function and
      revascularisation when co-transplanted as a composite pellet in a mouse model of
      diabetes.
AB  - AIMS/HYPOTHESIS: Hypoxia in the initial days after islet transplantation leads to
      considerable loss of islet mass and contributes to disappointing outcomes in the
      clinical setting. The aim of the present study was to investigate whether co
      transplantation of human non-endothelial bone marrow-derived multipotent adult
      progenitor cells (MAPCs), which are non-immunogenic and can secrete angiogenic
      growth factors during the initial days after implantation, could improve islet
      engraftment and survival. METHODS: Islets (150) were co-transplanted, with or
      without human MAPCs (2.5 * 105) as separate or composite pellets, under the
      kidney capsule of syngeneic alloxan-induced diabetic C57BL/6 mice. Blood glucose
      levels were frequently monitored and IPGTTs were carried out. Grafts and serum
      were harvested at 2 and 5 weeks after transplantation to assess outcome. RESULTS:
      Human MAPCs produced high amounts of angiogenic growth factors, including
      vascular endothelial growth factor, in vitro and in vivo, as demonstrated by the
      induction of neo-angiogenesis in the chorioallantoic membrane assay. Islet-human
      MAPC co-transplantation as a composite pellet significantly improved the outcome
      of islet transplantation as measured by the initial glycaemic control, diabetes
      reversal rate, glucose tolerance and serum C-peptide concentration compared with
      the outcome following transplantation of islets alone. Histologically, a higher
      blood vessel area and density in addition to a higher vessel/islet ratio were
      detected in recipients of islet-human MAPC composites.
      CONCLUSIONS/INTERPRETATION: The present data suggest that co-transplantation of
      mouse pancreatic islets with human MAPCs, which secrete high amounts of
      angiogenic growth factors, enhance islet graft revascularisation and subsequently
      improve islet graft function.

PMID- 27704165
TI  - The TetO rat as a new translational model for type 2 diabetic retinopathy by
      inducible insulin receptor knockdown.
AB  - AIMS/HYPOTHESIS: Although the renin-angiotensin system plays an important role in
      the progression of diabetic retinopathy, its influence therein has not been
      systematically evaluated. Here we test the suitability of a new translational
      model of diabetic retinopathy, the TetO rat, for addressing the role of
      angiotensin-II receptor 1 (AT1) blockade in experimental diabetic retinopathy.
      METHODS: Diabetes was induced by tetracycline-inducible small hairpin RNA (shRNA)
      knockdown of the insulin receptor in rats, generating TetO rats. Systemic
      treatment consisted of an AT1 blocker (ARB) at the onset of diabetes, following
      which, 4-5 weeks later the retina was analysed in vivo and ex vivo. Retinal
      function was assessed by Ganzfeld electroretinography (ERG). RESULTS: Retinal
      vessels in TetO rats showed differences in vessel calibre, together with gliosis.
      The total number and the proportion of activated mononuclear phagocytes was
      increased. TetO rats presented with loss of retinal ganglion cells (RGC) and ERG
      indicated photoreceptor malfunction. Both the inner and outer blood-retina
      barriers were affected. The ARB treated group showed reduced gliosis and an
      overall amelioration of retinal function, alongside RGC recovery, whilst no
      statistically significant differences in vascular and inflammatory features were
      detected. CONCLUSIONS/INTERPRETATION: The TetO rat represents a promising
      translational model for the early neurovascular changes associated with type 2
      diabetic retinopathy. ARB treatment had an effect on the neuronal component of
      the retina but not on the vasculature.

PMID- 27704166
TI  - GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings
      from a Bayesian meta-analysis.
AB  - AIMS/HYPOTHESIS: GAD is a major target of the autoimmune response that occurs in
      type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum
      vaccine in human participants have so far given conflicting results. METHODS: In
      this study, we sought to see whether a clearer answer to the question of whether
      GAD65 has an effect on C-peptide could be reached by combining individual-level
      data from the randomised controlled trials using Bayesian meta-analysis to
      estimate the probability of a positive biological effect (a reduction in C
      peptide loss compared with placebo approximately 1 year after the GAD vaccine).
      RESULTS: We estimate that there is a 98% probability that 20 MUg GAD with alum
      administered twice yields a positive biological effect. The effect is probably a
      15-20% reduction in the loss of C-peptide at approximately 1 year after
      treatment. This translates to an annual expected loss of between -0.250 and 
      0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of 
      0.294 pmol/ml at 1 year for untreated newly diagnosed patients.
      CONCLUSIONS/INTERPRETATION: The biological effect of this vaccination should be
      developed further in order to reach clinically desirable reductions in insulin
      loss in patients recently diagnosed with type 1 diabetes.

PMID- 27704167
TI  - Efficacy of single-hormone and dual-hormone artificial pancreas during continuous
      and interval exercise in adult patients with type 1 diabetes: randomised
      controlled crossover trial.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess whether the dual-hormone
      (insulin and glucagon) artificial pancreas reduces hypoglycaemia compared with
      the single-hormone (insulin alone) artificial pancreas during two types of
      exercise. METHODS: An open-label randomised crossover study comparing both
      systems in 17 adults with type 1 diabetes (age, 37.2 +/- 13.6 years; HbA1c, 8.0
      +/- 1.0% [63.9 +/- 10.2 mmol/mol]) during two exercise types on an ergocycle and
      matched for energy expenditure: continuous (60% [Formula: see text] for 60 min)
      and interval (2 min alternating periods at 85% and 50% [Formula: see text] for 40
      min, with two 10 min periods at 45% [Formula: see text] at the start and end of
      the session). Blocked randomisation (size of four) with a 1:1:1:1 allocation
      ratio was computer generated. The artificial pancreas was applied from 15:30
      hours until 19:30 hours; exercise was started at 18:00 hours and announced 20 min
      earlier to the systems. The study was conducted at the Institut de recherches
      cliniques de Montreal. RESULTS: During single-hormone control compared with dual
      hormone control, exercise-induced hypoglycaemia (plasma glucose <3.3 mmol/l with
      symptoms or <3.0 mmol/l regardless of symptoms) was observed in four (23.5%) vs
      two (11.8%) interventions (p = 0.5) for continuous exercise and in six (40%) vs
      one (6.25%) intervention (p = 0.07) for interval exercise. For the pooled
      analysis (single vs dual hormone), the median (interquartile range) percentage
      time spent at glucose levels below 4.0 mmol/l was 11% (0.0-46.7%) vs 0% (0-0%; p
      = 0.0001) and at glucose levels between 4.0 and 10.0 mmol/l was 71.4% (53.2-100%)
      vs 100% (100-100%; p = 0.003). Higher doses of glucagon were needed during
      continuous (0.126 +/- 0.057 mg) than during interval exercise (0.093 +/- 0.068
      mg) (p = 0.03), with no reported side-effects in all interventions.
      CONCLUSIONS/INTERPRETATION: The dual-hormone artificial pancreas outperformed the
      single-hormone artificial pancreas in regulating glucose levels during announced
      exercise in adults with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01930110 FUNDING: : Societe Francophone du Diabete and Diabete Quebec.

PMID- 27704168
TI  - Adverse drug events in patients with advanced chronic conditions who have a
      prognosis of limited life expectancy at hospital admission.
AB  - PURPOSE: Adverse drug events (ADEs) lead to adverse clinical outcomes such as
      hospitalization. There is little information about the characteristics of ADEs in
      patients with advanced chronic conditions and have a prognosis of limited life
      expectancy. This study aimed to evaluate (i) the prevalence of ADEs at the time
      of admission to hospital, (ii) the causality, severity, and preventability of the
      ADEs, and (iii) the clinical and pharmacological characteristics associated with
      the ADEs. METHODS: This is a prospective cross-sectional study (county of Osona,
      Catalonia, Spain). We included patients who required palliative care as
      identified by the NECPAL CCOMS-ICO tool who were hospitalized in an acute
      geriatric unit (AGU). A system of alerts (trigger tool) was used together with a
      multidisciplinary review for the detection of the ADEs. RESULTS: Over the course
      of 10 months, 235 patients were recruited. Seventy-six ADEs affecting 24.68 % of
      the sample were identified, and of these, 23 (30.26 % of the ADEs; 8.51 % of the
      sample) were directly related to hospitalization. The multivariate logistic
      regression analysis identified the following risk factors: presence of extreme
      polypharmacy (>=10 medications) (OR = 3.02; 95 % CI = 1.48-6.19), anticholinergic
      burden according to the Anticholinergic Drug Scale (ADS) (OR = 2.32; 95 % CI =
      1.13-4.78), and treatment complexity according to the Medication Regimen
      Complexity Index (MRCI) scale (OR = 2.90; 95 % CI = 1.44-5.83). The vast majority
      (94.45 %) of the ADEs were considered to be preventable. There were no
      differences in the survival of the patients. CONCLUSIONS: ADEs are common,
      largely preventable, and implicated in the hospitalization of patients who
      require palliative care.

PMID- 27704169
TI  - Hepatic expression of transcription factors affecting developmental regulation of
      UGT1A1 in the Han Chinese population.
AB  - PURPOSE: Complete or partial inactivity of UGT1A1, the unique enzyme responsible
      for bilirubin glucuronidation, is commonly associated with hyperbilirubinemia. We
      investigated the dynamic expression of UGT1A1, and that of the transcription
      factors (TFs) involved in its developmental regulation, during human hepatic
      growth in Han Chinese individuals. METHODS: Eighty-eight prenatal, pediatric, and
      adult liver samples were obtained from Han Chinese individuals. Quantitative real
      time polymerase chain reaction was used to evaluate mRNA expression of UGT1A1 and
      TFs including PXR, CAR, HNF1A, HNF4A, PPARA, etc. UGT1A1 protein levels and
      metabolic activity were determined by western blotting and high-performance
      liquid chromatography. Direct sequencing was employed to genotype UGT1A1*6
      (211G?A) and UGT1A1*28 (TA6?TA7) polymorphisms. RESULTS: UGT1A1 expression was
      minimal in prenatal samples, but significantly elevated during pediatric and
      adult stages. mRNA and protein levels and metabolic activity were prominently
      increased (120-, 20-, and 10-fold, respectively) in pediatric and adult livers
      compared to prenatal samples. Furthermore, expression did not differ appreciably
      between pediatric and adult periods. Dynamic expression of TFs, including PXR,
      CAR, HNF1A, HNF4A, and PPARA, was consistent with UGT1A1 levels at each
      developmental stage. A pronounced correlation between expression of these TFs and
      that of UGT1A1 (P < 0.001) was observed. Moreover, UGT1A1*6 and UGT1A1*28
      polymorphisms reduced levels of UGT1A1 by up to 40-60 %. CONCLUSIONS: Hepatic
      expression of transcription factors is associated with developmental regulation
      of UGT1A1 in the Han Chinese population. Moreover, UGT1A1 polymorphisms are
      associated with reduced expression of UGT1A1 mRNA and protein, as well as enzyme
      activity.

PMID- 27704171
TI  - Adaptive Capacity in Community Forest Management: A Systematic Review of Studies
      in East Asia.
AB  - This study investigated the indicators of adaptive capacity along with
      disturbances in community forest management systems in the East Asian countries,
      China, Japan and South Korea. Although these countries have centuries-old
      traditions of community-based forest management, they have been less researched
      in light of adaptive capacity for resilient social-ecological systems. Recent
      social and ecological disturbances bring about new challenges and/or
      opportunities to the capacity of forest related communities to adapt to rapidly
      changing conditions. Through a systematic review of the community forestry and
      related adaptive capacity literature in three East Asian countries, this study
      addressed the role of diverse knowledge systems, such as traditional and Western
      scientific knowledge, and civic traditions of self-organization in local
      communities that characterized adaptive capacity of this region. This study
      extends our understanding of community-based conservation efforts and traditions
      of this region, and adds to the understandings gleaned from studies of community
      forestry in the West and sacred forests in other parts of Asia and Africa.
      Further research on ways to increase adaptive capacity is needed in a site
      specific context.

PMID- 27704170
TI  - Memory and adaptive behavior in population dynamics: anti-predator behavior as a
      case study.
AB  - Memory allows organisms to forecast the future on the basis of experience, and
      thus, in some form, is important for the development of flexible adaptive
      behavior by animal communities. To model memory, we use the concept of
      hysteresis, which mathematically is described by the Preisach operator. As a case
      study, we consider anti-predator adaptation in the classic Lotka-Volterra
      predator-prey model. Despite its simplicity, the model allows us to naturally
      incorporate essential features of an adaptive system and memory. Our analysis and
      simulations show that a system with memory can have a continuum of equilibrium
      states with non-trivial stability properties. The main factor that determines the
      actual equilibrium state to which a trajectory converges is the maximal number
      achieved by the population of predator along this trajectory.

PMID- 27704172
TI  - Improvement of Postoperative Pain Control Processes and Outcomes in Veterans of a
      Surgical Intensive Care Unit.
AB  - BACKGROUND: Postoperative pain remains undertreated in critically ill patients.
      We hypothesized that the adequacy of pain control in our Surgical Intensive Care
      Unit (SICU) was above the reported average of 71 % in the literature and that the
      introduction of the critical care pain observation tool (CPOT) could improve it.
      We used a Lean Six Sigma methodology to improve our processes and quantify our
      improvement. PATIENTS AND METHODS: We retrospectively review 713 consecutive
      veterans admitted to our SICU. Between December 2014 and February 2015,
      postoperative pain was assessed every 2 h and rated "acceptable," "unacceptable,"
      or "unable to assess". Between March 2015 and October 2015, postoperative pain
      was assessed with CPOT. Concurrently, we implemented a postoperative pain
      education program and documented this activity in the electronic medical record.
      RESULTS: The baseline adequacy of pain control was 78 %, which improved to 99 %
      after the introduction of CPOT. We concurrently achieved a 100 % median
      documentation of postoperative pain education in the electronic medical record.
      The introduction of CPOT improved the process sigma from 2.3 to 3.8. The process
      of documenting pain education achieved a process sigma of 3.1. CONCLUSIONS: The
      proportion of veterans with acceptable pain control in our SICU is higher than
      that reported in the literature and the application of a Six Sigma methodology
      that involved the introduction of the CPOT has allowed us to improve the
      perception of pain control and comply with the newest regulatory directives.

PMID- 27704173
TI  - The biophysics, biochemistry and physiology of CFTR.

PMID- 27704175
TI  - Cadmium(II)-based metal-organic nanotubes as solid-phase microextraction coating
      for ultratrace-level analysis of polychlorinated biphenyls in seawater samples.
AB  - In this study, stable cadmium(II)-based metal-organic nanotubes (Cd-MONTs) were
      prepared and used as a coating material for solid-phase microextraction (SPME) of
      polychlorinated biphenyls (PCBs) from environmental water samples. The as
      prepared Cd-MONT SPME coating material was characterized by thermal gravimetric
      analysis, scanning electron microscopy, and X-ray diffraction. The synthesized Cd
      MONTs exhibited high thermal stability (385  degrees C) and excellent extraction
      performance toward PCBs. The important conditions were optimized systematically
      by the response surface method. Under the optimal conditions, the new fiber
      achieved high enrichment factors (938-3417), low limits of detection (1.80-8.73
      pg L-1), and wide linearity (10-5000 pg L-1). The method developed was used in
      ultratrace-level analysis of PCBs in seawater samples, with satisfactory results
      for each sample.

PMID- 27704174
TI  - CFTR pharmacology.
AB  - CFTR protein is an ion channel regulated by cAMP-dependent phosphorylation and
      expressed in many types of epithelial cells. CFTR-mediated chloride and
      bicarbonate secretion play an important role in the respiratory and
      gastrointestinal systems. Pharmacological modulators of CFTR represent promising
      drugs for a variety of diseases. In particular, correctors and potentiators may
      restore the activity of CFTR in cystic fibrosis patients. Potentiators are also
      potentially useful to improve mucociliary clearance in patients with chronic
      obstructive pulmonary disease. On the other hand, CFTR inhibitors may be useful
      to block fluid and electrolyte loss in secretory diarrhea and slow down the
      progression of polycystic kidney disease.

PMID- 27704176
TI  - Real-time monitoring of oxidative injury of vascular endothelial cells and
      protective effect of quercetin using quartz crystal microbalance.
AB  - The adhesion, spreading, and proliferation of human umbilical vein endothelial
      cell line (HUVEC-C) cells, on a gold electrode were monitored using quartz
      crystal microbalance (QCM) measurements. The viscodensity effect caused by the
      normal action of the cells led to a decrease of the resonant frequency and
      increase of the motional resistance. The oxidative injury of HUVEC-C cells
      appeared immediately with the addition of H2O2, exhibiting the decline of
      cellular spreading area and cell coverage on the electrode surface and resulting
      in inverted QCM responses. The injured extent of the cells was found to be
      related to the content of H2O2. It is found that 0.05 mM quercetin added
      beforehand in the growth medium could remove completely the oxidative action of
      1.0 mM H2O2. Quercetin with increased dosage still exerted a partial protective
      effect on HUVEC-C cells against oxidative injury induced by 2.5 mM H2O2. The
      microscope observations, electrochemical measurements, and MTT analysis validate
      the QCM assay results, indicating that quercetin is a valuable flavonoid anti
      oxidant in the precaution and treatment for the oxidative injury of vascular
      endothelium. Graphical Abstract Upper part: Microscope images (*400) of 7.5*104
      HUVEC-C cells adhered to the substrate at 48 h in the presence of H2O2. Middle
      part: Real-time Deltaf 0 and DeltaR 1 responses to the addition of 7.5*104 HUVEC
      C cells onto QCM gold electrode in the presence of H2O2 added at 24 h after the
      introduction of the cells. Lower part: Microscope images (*400) of 7.5*104 HUVEC
      C cells adhered to the substrate at 48 h in the presence of quercetin added at 18
      h and H2O2 added at 24 h after the introduction of the cells.

PMID- 27704178
TI  - Study of in-vitro metabolism of selected antibiotic drugs in human liver
      microsomes by liquid chromatography coupled with tandem mass spectrometry.
AB  - High performance liquid chromatography coupled with triple-quadrupole mass
      spectrometry was applied in the determination of in vitro metabolism products of
      selected antibiotic drugs (cefotaxime, ciprofloxacin, fluconazole, gentamicin,
      clindamycin, linezolid, and metronidazole). The analytes were separated on a
      reversed phase C18 column, with acetonitrile and 0.1 % aqueous formic acid as the
      mobile phase. Tandem mass spectrometry with positive electrospray ionization was
      used to facilitate the structural characterization of the potential metabolites.
      Metabolism studies on human liver microsomes were performed via cytochromes P450
      (phase I) and via NADPH/UDP-glucuronosyltransferase (phase II) mediated
      reactions. LC-MS/MS experiments allowed potential metabolite peaks, including sum
      formulae suggestions, to be identified; high resolution MS/MS experiments led to
      the identification of various oxidative and reductive modifications of target
      compounds in phase I biotransformation, and conjugation products with glucuronic
      acid in phase II reactions. A total of 11 potential metabolites and their
      proposed structures were characterized during the incubation of human liver
      microsomes by comparing their retention times and spectral patterns with those of
      the parent drug. Dehydrogenation and reactions of side chains such as
      hydroxylation and hydrolysis of ester bonds constituted the major metabolic
      pathways. Finally, LC-MS/MS spectrometry was revealed to be a suitable analytical
      tool to procure a feasible analytical base for the envisioned in vivo
      experiments. Graphical Abstract Workflow overview of in vitro drug metabolism
      studies.

PMID- 27704179
TI  - Map-based cloning of the dominant genic male sterile Ms-cd1 gene in cabbage
      (Brassica oleracea).
AB  - KEY MESSAGE: Using map-based cloning, we delimited the Ms - cd1 gene responsible
      for the male sterile phenotype in B. oleracea to an approximately 39-kb fragment.
      Expression analysis suggests that a new predicted gene, a homolog of the
      Arabidopsis SIED1 gene, is a potential candidate gene. A dominant genic male
      sterile (DGMS) mutant 79-399-3 in Brassica oleracea (B. oleracea) is controlled
      by a single gene named Ms-cd1, which was genetically mapped on chromosome C09.
      The derived DGMS lines of 79-399-3 have been successfully applied in hybrid
      cabbage breeding and commercial hybrid seed production of several B. oleracea
      cultivars in China. However, the Ms-cd1 gene responsible for the DGMS has not
      been identified, and the molecular basis of the DGMS is unclear, which then
      limits its widespread application in hybrid cabbage seed production. In the
      present study, a large BC9 population with 12,269 individuals was developed for
      map-based cloning of the Ms-cd1 gene, and Ms-cd1 was mapped to a 39.4-kb DNA
      fragment between two InDel markers, InDel14 and InDel24. Four genes were
      identified in this region, including two annotated genes based on the available
      B. oleracea annotation database and two new predicted open reading frames (ORFs).
      Finally, a newly predicted ORF designated Bol357N3 was identified as the
      candidate of the Ms-cd1 gene. These results will be useful to reveal the
      molecular mechanism of the DGMS and develop more practical DGMS lines with stable
      male sterility for hybrid seed production in cabbage.

PMID- 27704180
TI  - A simple method for isolation and construction of markerless cyanobacterial
      mutants defective in acyl-acyl carrier protein synthetase.
AB  - Cyanobacterial mutants defective in acyl-acyl carrier protein synthetase (Aas)
      secrete free fatty acids (FFAs) into the external medium and hence have been used
      for the studies aimed at photosynthetic production of biofuels. While the wild
      type strain of Synechocystis sp. PCC 6803 is highly sensitive to exogenously
      added linolenic acid, mutants defective in the aas gene are known to be resistant
      to the externally provided fatty acid. In this study, the wild-type Synechocystis
      cells were shown to be sensitive to lauric, oleic, and linoleic acids as well,
      and the resistance to these fatty acids was shown to be enhanced by inactivation
      of the aas gene. On the basis of these observations, we developed an efficient
      method to isolate aas-deficient mutants from cultures of Synechocystis cells by
      counter selection using linoleic acid or linolenic acid as the selective agent. A
      variety of aas mutations were found in about 70 % of the FFA-resistant mutants
      thus selected. Various aas mutants were isolated also from Synechococcus sp. PCC
      7002, using lauric acid as a selective agent. Selection using FFAs was useful
      also for construction of markerless aas knockout mutants from Synechocystis sp.
      PCC 6803 and Synechococcus sp. PCC 7002. Thus, genetic engineering of FFA
      producing cyanobacterial strains would be greatly facilitated by the use of the
      FFAs for counter selection.

PMID- 27704181
TI  - Reduction of ammonia and lactate through the coupling of glutamine synthetase
      selection and downregulation of lactate dehydrogenase-A in CHO cells.
AB  - Chinese hamster ovary (CHO) cell cultivation for production of therapeutic
      proteins is accompanied by production of metabolic wastes, mostly ammonia and
      lactate. To reduce ammonia production, the glutamine synthetase (GS) system was
      used to develop therapeutic monoclonal antibody (mAb)-producing CHO cells (SM
      0.025). Additionally, the lactate dehydrogenase-A (LDH-A) was downregulated with
      shRNA to reduce lactate production in SM-0.025. The resulting mAb-producing cell
      lines (#2, #46, and #52) produced less ammonia than the host cell line during the
      exponential phase due to GS protein overexpression. LDH-A downregulation in SM
      0.025 not only reduced lactate production but also further reduced ammonia
      production. Among the three LDH-A-downregulated clones, clone #2 had the highest
      mAb production along with significantly reduced specific lactate and ammonia
      production rates compared to those in SM-0.025. Waste reduction increased the
      galactosylation level of N-glycosylation, which improved mAb quality. LDH-A
      downregulation was also successfully applied to the host cell lines (CHO K1 and
      GS knockout CHO-K1). However, LDH-A downregulated host cells could not survive
      the pool-selection process wherein glutamine was excluded and methionine
      sulfoximine was added to the media. Taken together, LDH-A downregulation in the
      mAb-producing cell line generated with the GS system successfully reduced both
      ammonia and lactate levels, improving mAb galactosylation. However, LDH-A
      downregulation could not be applied to host cell lines because it hampered the
      selection process of the GS system.

PMID- 27704182
TI  - Characterization of LnmO as a pathway-specific Crp/Fnr-type positive regulator
      for leinamycin biosynthesis in Streptomyces atroolivaceus and its application for
      titer improvement.
AB  - The cyclic adenosine monophosphate (cAMP) receptor protein/fumarate and nitrate
      reductase regulatory protein (Crp/Fnr) family of transcriptional regulators are
      pleiotropic transcriptional regulators that control a broad range of cellular
      functions. Leinamycin (LNM) is a potent antitumor antibiotic produced by
      Streptomyces atroolivaceus S-140. We previously cloned and characterized the lnm
      biosynthetic gene cluster from S. atroolivaceus S-140. We here report
      inactivation of lnmO in S. atroolivaceus S-140 and overexpression of lnmO in the
      S. atroolivaceus S-140 wild-type and ?lnmE mutant SB3033 to investigate its role
      in LNM biosynthesis. Bioinformatics analysis revealed LnmO as the only regulator
      within the lnm gene cluster, exhibiting high sequence similarity to known Crp/Fnr
      family regulators. The inactivation of lnmO in S. atroolivaceus S-140 completely
      abolished LNM production but caused no apparent morphological changes, supporting
      that LnmO is indispensable and specific to LNM biosynthesis. Overexpression of
      lnmO in S. atroolivaceus S-140 and SB3033 resulted in three- and fourfold
      increase in LNM and LNM E1 production, respectively, supporting that LnmO acts as
      a positive regulator. While all of the Crp/Fnr family regulators studied to date
      appeared to be pleiotropic, our results support LnmO as the first Crp/Fnr family
      regulator that is pathway-specific. LnmO joins the growing list of regulators
      that could be exploited to improve secondary metabolite production in
      Streptomyces. Engineered strains overproducing LNM and LNM E1 will facilitate
      further mechanistic studies and clinical evaluation of LNM and LNM E1 as novel
      anticancer drugs.

PMID- 27704183
TI  - Autoimmune arthritis deteriorates bone quantity and quality of periarticular bone
      in a mouse model of rheumatoid arthritis.
AB  - : This study showed that autoimmune arthritis induces especially severe
      osteoporosis in the periarticular region adjacent to inflamed joints, suggesting
      that arthritis increases the fragility fracture risk near inflamed joints, which
      is frequently observed in patients with RA. INTRODUCTION: Periarticular
      osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis
      (RA). Here we show that rheumatic inflammation deteriorates the bone quality and
      bone quantity of periarticular bone, thereby decreasing bone strength and
      toughness in a mouse model of RA. METHODS: Female BALB/c mice and SKG mice, a
      mutant mouse model of autoimmune arthritis on the BALB/c background, were used.
      At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral
      ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to
      induce arthritis. Eight weeks later, the mice were killed and the femurs and
      tibias were subjected to micro-computed tomography, Fourier transform infrared
      (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical
      testing. RESULTS: SKG mice developed significant trabecular bone loss in both the
      distal metaphysis of the femur and the lumbar vertebral body, but the extent of
      the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice
      exhibited changes in the geometry and matrix properties of the diaphysis of the
      femur, whereas SKG mice, but not OVX mice, did exhibit changes in these
      properties in the distal metaphysis of the femur. Bone strength and fracture
      toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle
      joint were significantly decreased in SKG mice. CONCLUSIONS: Autoimmune arthritis
      induces periarticular osteoporosis, characterized by deterioration of cortical
      bone geometry and quality as well as by trabecular bone loss, leading to severe
      bone fragility in periarticular bone adjacent to inflamed joints.

PMID- 27704184
TI  - Mini-percutaneous nephrolithotomy for stones in anomalous-kidneys: a prospective
      study.
AB  - To evaluate safety and efficacy of minipercutaneous nephrolithotomy (Mini-PNL) in
      management of stones in different types of renal anomalies. Patients with stones
      >=2 cm or SWL-resistant stones in anomalous-kidneys treated by Mini-PNL between
      March 2010 and September 2012 were included prospectively. Mini-PNL was done
      under regional anesthesia in prone position with fluoroscopic guidance through 18
      Fr sheath using semirigid ureteroscope (8.5/11.5 Fr) and pneumatic lithotripter.
      All patients were followed-up for 2-3 years. Stone-free rate was defined as
      absence of residual fragments >=2 mm. Student-T, Mann-Whitney, Chi square (chi
      2), Fisher-exact, one way ANOVA or Kruskal-Wallis test were used for analysis.
      Mini-PNL was performed for 59 patients (20 horseshoe, 15 malrotated, 7
      polycystic, 13 duplex and 4 ectopic pelvic-kidneys). Mean age was 40.18 +/- 12.75
      (14-78) years. Mean stone burden was 31.72 +/- 21.43 (7.85-141.3) mm2. Two tracts
      were required in 7 (11.9 %) patients. Tubeless Mini-PNL with double-J insertion
      was performed in all patients except two. Operative time was 50.17 +/- 18.73 (15
      105) min. Hemoglobin loss was 0.44 +/- 0.30 (0-1.4) g/dL. Complications were
      reported in 15 (25.4 %) patients. No pleural injury, sepsis, perinephric
      collection or renal-pelvis perforation were reported. Stone-free rate was 89.8 %
      (converted to open-surgery in one patient, second-look PNL in two patients,
      auxiliary SWL in three patients). Stone-free rate improved to 98.3 % after
      retreatment and auxiliary SWL. Site of puncture was mostly upper calyceal in
      horseshoe-kidney (80 %), mid calyceal in polycystic-kidney (85.7 %) and lower
      calyceal in duplex-kidney (46.2 %). Punctures were also significantly infracostal
      in horseshoe-kidney (100 %) and supracostal in both duplex (53.8 %) and
      malrotated-kidneys (66.7 %). Mini-PNL is safe for management of stones in
      anomalous-kidney with SFR comparable to standard-PNL but with less complications.

PMID- 27704185
TI  - Emerging Concern from Short-Term Textile Leaching: A Preliminary Ecotoxicological
      Survey.
AB  - Textile dyes and their residues gained growing attention worldwide. Textile
      industry is a strong water consumer potentially releasing xenobiotics from
      washing and rinsing procedures during finishing processes. On a decentralised
      basis, also final consumers generate textile waste streams. Thus, a procedure
      simulating home washing with tap water screened cotton textiles leachates (n =
      28) considering physico-chemical (COD, BOD5, and UV absorbance) and
      ecotoxicological data (Daphnia magna, Pseudokirchneriella subcapitata and
      Lepidium sativum). Results evidenced that: (i) leachates presented low
      biodegradability levels; (ii) toxicity in more than half leachates presented
      slight acute or acute effects; (iii) the remaining leachates presented "no
      effect" suggesting the use of green dyes/additives, and/or well established
      finishing processes; (iv) no specific correlations were found between traditional
      physico-chemical and ecotoxicological data. Further investigations will be
      necessary to identify textile residues, and their potential interactions with
      simulated human sweat in order to evidence potential adverse effects on human
      health.

PMID- 27704186
TI  - Effect of Pretilachlor on Soil Enzyme Activities in Tropical Rice Soil.
AB  - Pretilachlor treatments, namely, recommended dose at 600 g a.i. ha-1 (RD), double
      the recommended dose at 1200 g a.i. ha-1 (2RD), ten times of the recommended dose
      at 6000 g a.i. ha-1 (10RD) along with control, were used to study the effects of
      pretilachlor on soil enzymes in tropical rice soil. Pretilachlor, at recommended
      dose completely dissipated 30 days after herbicide application. Twenty days after
      herbicide application, the dehydrogenase activity was inhibited up to 27 %, 28 %
      and 40 % of initial values of RD, 2RD and 10RD treatments, respectively. Increase
      in fluorescein diacetate hydrolase activity was observed during the first 25 days
      post herbicide application up to 29 %, 36 % and 10 % of initial values of RD, 2RD
      and 10RD treatments, respectively. beta-Glucosidase activity in the experiment
      did not provide a specific trend. In general, urease and acid phosphatase
      activities were not influenced by pretilachlor application. There were
      significant differences in alkaline phosphatase activities among the treatments
      until 25 days after herbicide application. Hence, pretilachlor may cause short
      term transitory changes in soil enzyme parameters. However, it has negative
      impact on soil enzymes at very high dose.

PMID- 27704187
TI  - Long-Term Survey of Cadmium and Lead Contamination in Japanese Black Bears
      Captured in Iwate Prefecture, Japan.
AB  - Cadmium and lead were measured in liver and kidney samples of 242 Japanese black
      bears (Ursus thibetanus japonicus) captured from 1999 to 2014 from two local
      populations in Japan. The median concentration of cadmium was 0.54 (mean: 0.80)
      mg/kg-w.w. in liver and 7.7 (mean: 11.8) mg/kg-w.w. in kidney. The median
      concentration of lead was 0.24 (mean: 0.40) and 0.21 (mean: 0.32) mg/kg-w.w. in
      liver and kidney, respectively. Bears in the Kita-ou local population had higher
      concentrations of cadmium and lead than those in the Kitakami Highlands local
      population. No chronological change was observed in cadmium levels in tissues,
      but the percentage of bears whose lead levels exceeded 0.5 mg/kg-w.w. has been
      decreasing in recent years. Countermeasures against lead poisoning in wildlife,
      which were instituted in 2002, may have contributed to the decrease in lead
      contamination of the Japanese black bear.

PMID- 27704188
TI  - Toxicity of CuO Nanoparticles to Structure and Metabolic Activity of Allium cepa
      Root Tips.
AB  - Roots of Allium cepa were exposed to six CuO NPs suspensions (0, 5, 10, 20, 40,
      80 mg L-1) in this study. Results revealed that with the increase of CuO NPs
      concentration, the Cu content in roots increased significantly. Compared to
      control, onion roots treated with CuO NPs (except 5 mg L-1 suspension) grew
      slowly after 24 h. The surface of the root cap and meristematic zone were
      obviously damaged. The apical meristem of roots treated by 10 mg L-1 and above
      concentrations stopped division. The nucleus of meristematic cells deformed, and
      nucleoli number increased. The plasmolysis occurred, and the cell membrane and
      nuclear membrane fractured. With the increase of CuO NPs concentration, the MDA
      content increased, and the root activity decreased. When dealt with 80 mg L-1 CuO
      NPs for 72 h, onion roots appeared to be corroded.

PMID- 27704189
TI  - Sublethal Effects of Chlorine-Free Kraft Mill Effluents on Daphnia magna.
AB  - The implementation of elemental chlorine-free (ECF) bleaching methods has
      drastically reduced the aquatic toxicity of Kraft mill effluents during the last
      decade. However, the residual toxicity of Kraft mill effluents is still a
      potential concern for the environment, even when subjected to secondary
      wastewater treatment. The aim of this study is characterize potential sublethal
      effects of ECF Kraft mill effluents using Daphnia magna as model species. D.
      magna exposed towards increasing concentration of ECF Kraft mill effluent showed
      a significant, dose-dependent reduction in feeding. Conversely, post-feeding
      assay, life history, and allometric growth analyses showed stimulatory, rather
      than inhibitory effects in exposed animals at low concentrations, while high
      concentrations of ECF Kraft mill effluents reduced their reproductive output.
      These results suggest a hormetic effect in which moderate concentrations of the
      effluent had a stimulatory effect with higher concentrations causing inhibition
      in some variables.

PMID- 27704190
TI  - Chromium Displacement in Subtropical Soils Fertilized with Hydrolysed Leather: A
      Laboratory Study.
AB  - Prolonged use of biosolids with high metal content may result in diffuse
      pollution across large regions, especially if such ions can move freely through
      the soil profile and reach underground water sources. The objective of this study
      was to verify whether Cr added to the soil surface in the form of hydrolysed
      leather or a soluble salt would migrate over significant distances in four
      subtropical soils differing in physical, chemical and mineralogical properties.
      Horizontal and vertical mobility were assessed in Petri dishes and small pots,
      respectively, using low (12 mg kg-1 soil) and high Cr levels (150 mg kg-1 soil)
      added to the soil surface. Irrespective of concentration, soluble Cr salts were
      found to move more easily in soils with low organic matter and clay content.
      Contrarily, Cr added as hydrolysed leather exhibited negligible mobility and
      tended to accumulate in the vicinity of application.

PMID- 27704191
TI  - Periarticular joint infection: Survey of the European Knee Associates (EKA) of
      ESSKA.

PMID- 27704192
TI  - A rare case of rectal carcinoma and prostate carcinoma with coexistent Paget's
      disease mimicking bone metastases in both 18F-FDG and 68Ga PSMA PET/CT.

PMID- 27704193
TI  - Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine
      patients treated with 177Lu-D OTATATE.
AB  - PURPOSE: Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated
      pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important
      prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of
      FDG PET in 60 patients with advanced P-NETs. METHODS: From March 2008 to June
      2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up
      lasted until March 2016. Eligible patients were treated with two different total
      cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6-8 weeks), according
      to kidney and bone marrow parameters. RESULTS: Twenty-eight patients received a
      mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5
      GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in
      the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS)
      was 53.4 months in the FA group and 21.7 months in the RA group (P = 0.353).
      Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8
      months in the RA group (P = 0.007). Fifty-five patients underwent an FDG PET scan
      before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS
      was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET
      negative group (P < 0.0002), regardless of the total activity administered.
      CONCLUSION: Both FA and RA are active in patients undergoing Lu-PRRT. However, an
      FA of 27.8 GBq of Lu-PRRT prolongs PFS and OS compared to an RA of 18.5 GBq. Our
      results indicate that FDG PET is an independent prognostic factor in this patient
      setting.

PMID- 27704194
TI  - [18F]FDG PET accurately differentiates infected and non-infected non-unions after
      fracture fixation.
AB  - PURPOSE: Complete fracture healing is crucial for good patient outcomes. A major
      complication in the treatment of fractures is non-union. The pathogenesis of non
      unions is not always clear, although implant-associated infections play a
      significant role, especially after surgical treatment of open fractures. We aimed
      to evaluate the value of [18F]FDG PET in suspected infections of non-union
      fractures. METHODS: We retrospectively evaluated 35 consecutive patients seen
      between 2000 and 2015 with suspected infection of non-union fractures, treated at
      a level I trauma center. The patients underwent either [18F]FDG PET/CT (N = 24),
      [18F]FDG PET (N = 11) plus additional CT (N = 8), or conventional X-ray (N = 3).
      Imaging findings were correlated with final diagnosis based on intraoperative
      culture or follow-up. RESULTS: In 13 of 35 patients (37 %), infection was proven
      by either positive intraoperative tissue culture (N = 12) or positive follow-up
      (N = 1). [18F]FDG PET revealed 11 true-positive, 19 true-negative, three false
      positive, and two false-negative results, indicating sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV), and accuracy of
      85 %, 86 %, 79 %, 90 %, and 86 %, respectively. The SUVmax was 6.4 +/- 2.7 in the
      clinically infected group and 3.0 +/- 1.7 in the clinically non-infected group (p
      <0.01). The SUVratio was 5.3 +/- 3.3 in the clinically infected group and 2.6 +/-
      1.5 in the clinically non-infected group (p <0.01). CONCLUSION: [18F]FDG PET
      differentiates infected from non-infected non-unions with high accuracy in
      patients with suspected infections of non-union fractures, for whom other
      clinical findings were inconclusive for a local infection. [18F]FDG PET should be
      considered for therapeutic management of non-unions.

PMID- 27704195
TI  - Tracheocutaneous Fistula Closure: Comparison of Rhomboid Flap Repair with Z
      Plasty Repair in a Case Series of 40 Patients.
AB  - INTRODUCTION: Tracheocutaneous fistula (TCF) is one of the recognized sequelae of
      a long-term tracheostomy resulting from mucocutaneous overgrowth which prevents
      closure of the artificial lumen at the site of tracheostomy. Primary closure of
      TCF has disappointing results and may lead to complications like pneumothorax,
      pneumomediastinum, cervicofacial subcutaneous emphysema, and depressed scar.
      OBJECTIVE: To compare TCF repair using fistulectomy followed by rhomboid flap
      versus fistulectomy followed by Z plasty repair. METHODS: In this prospective
      study, 40 patients of either sex with persistent TCF were included. All patients
      were randomly divided into two groups. Group I had 20 patients who underwent TCF
      repair using a technique in which fistulectomy was done followed by its closure
      in layers, and finally closing the defect using a rhomboid flap. The remaining 20
      were included in group II who underwent TCF repair using a technique in which
      fistulectomy was done followed by layered closing, and final closure of the
      defect was done using Z plasty. The follow-up period was 3 months. RESULTS: Out
      of 40 patients, all but 8 experienced a successful outcome without any
      complications, and complete aesthetic satisfaction, with improvement in
      phonation, and no soiling of clothes with mucus or sputum. The 8 unsuccessful
      patients belonged to group II (Z plasty group). CONCLUSION: Both techniques have
      been described in the literature and are proven to give good results. Our study
      emphasizes the fact that in our experience, the rhomboid flap was a better
      alternative for TCF repair than Z plasty. 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- 27704196
TI  - Scarless Epicanthoplasty and Concomitant Double Eyelidplasty in Chinese Eyelids.
AB  - BACKGROUND: The presence of mild or moderate medial epicanthus is typical in
      Asian patients. Numerous epicanthoplasty techniques have been described
      previously. However, these methods usually leave obvious scars in the medial
      canthal area. The aim of this report is to introduce a novel epicanthoplasty
      technique and a concomitant double eyelidplasty which avoid leaving scars in the
      medial canthal region. METHODS: From July 2013 to July 2015, 252 patients
      received epicanthoplasty and concomitant double eyelidplasty with this new
      technique. The medial epicanthus was corrected through the medial end of the
      eyelid crease incision. One hundred eighteen of these patients were followed up
      for 3-24 months (8 months in average). The preoperative and postoperative
      interepicanthal distances were measured at pre, 3 and 6 months post-operation.
      The aesthetic results were evaluated with patient visual analog scale (VAS)
      scores. RESULTS: The average intercanthal distance significantly decreased 3
      months after the operation (32.7 +/- 2.3 mm vs 36.5 +/- 2.6 mm, p < 0.05, paired
      t test). Little retraction was noticed at 6 months after the operation (33.0 +/-
      2.4 vs 32.7 +/- 2.3 mm, p < 0.05, paired t test). The mean patient VAS score
      associated with satisfaction of overall outcome was 4.2 at 6 months after
      operation (range 2.5-5.0). CONCLUSION: This new method provides an effective way
      to correct the medial epicanthus without leaving any scar in the medial canthal
      region. Patients with mild to moderate medial epicanthus are good candidates for
      this procedure. 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- 27704197
TI  - A Simple and Effective Technique of Breast Remodelling After Conserving Surgery
      for Lower Quadrants Breast Cancer.
AB  - BACKGROUND: Quadrantectomy is an oncologically safe procedure for the treatment
      of early-stage breast cancer, but it often results in poor aesthetic outcomes
      such as breast shape deformity, which is more visible if the tumour is located in
      the lower pole. We recommend the use of the transverse incision, which retains
      the oncological advantages of the quadrantectomy while leading to better
      aesthetical results. METHOD: We evaluated the clinical results of 24 patients
      with breast cancer who underwent quadrantectomy of the lower breast pole and
      volume replacement with remodelling through three posterior scorings from January
      2012 to January 2014, with cosmetic evaluations performed according to the
      criteria set by the Japanese Breast Cancer Society. RESULTS: Minimum follow-up
      after surgery was 2 years, with an average of 28.4 months. Among treated
      patients, the percentage of complications was extremely low and the degree of
      satisfaction fairly good. Moreover, the assessment of the medical team matched
      patient self-assessments. CONCLUSION: Immediate breast reconstruction of a defect
      performed after a quadrantectomy of the lower breast pole using the "posterior
      scoring technique" provided better cosmetic results compared to the transposition
      of residual breast tissue. This technique provides reliable and reproducible
      results, and it also appears to be rather successful on patients with small
      moderate breasts in the absence of a certain degree of ptosis, therefore
      increasing its already considerable appeal. LEVEL OF EVIDENCE V: This journal
      requires that the 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- 27704198
TI  - Diagnostic value of transmural perfusion ratio derived from dynamic CT-based
      myocardial perfusion imaging for the detection of haemodynamically relevant
      coronary artery stenosis.
AB  - OBJECTIVES: To investigate the additional value of transmural perfusion ratio
      (TPR) in dynamic CT myocardial perfusion imaging for detection of
      haemodynamically significant coronary artery disease compared with fractional
      flow reserve (FFR). METHODS: Subjects with suspected or known coronary artery
      disease were prospectively included and underwent a CT-MPI examination. From the
      CT-MPI time-point data absolute myocardial blood flow (MBF) values were
      temporally resolved using a hybrid deconvolution model. An absolute MBF value was
      measured in the suspected perfusion defect. TPR was defined as the ratio between
      the subendocardial and subepicardial MBF. TPR and MBF results were compared with
      invasive FFR using a threshold of 0.80. RESULTS: Forty-three patients and 94
      territories were analysed. The area under the receiver operator curve was larger
      for MBF (0.78) compared with TPR (0.65, P = 0.026). No significant differences
      were found in diagnostic classification between MBF and TPR with a territory
      based accuracy of 77 % (67-86 %) for MBF compared with 70 % (60-81 %) for TPR.
      Combined MBF and TPR classification did not improve the diagnostic
      classification. CONCLUSIONS: Dynamic CT-MPI-based transmural perfusion ratio
      predicts haemodynamically significant coronary artery disease. However,
      diagnostic performance of dynamic CT-MPI-derived TPR is inferior to quantified
      MBF and has limited incremental value. KEY POINTS: * The transmural perfusion
      ratio from dynamic CT-MPI predicts functional obstructive coronary artery disease
      * Performance of the transmural perfusion ratio is inferior to quantified
      myocardial blood flow * The incremental value of the transmural perfusion ratio
      is limited.

PMID- 27704199
TI  - Evaluation of Chondrocalcinosis and Associated Knee Joint Degeneration Using MR
      Imaging: Data from the Osteoarthritis Initiative.
AB  - OBJECTIVES: To evaluate the ability of different MRI sequences to detect
      chondrocalcinosis within knee cartilage and menisci, and to analyze the
      association with joint degeneration. METHODS: Subjects with radiographic knee
      chondrocalcinosis (n = 90, age 67.7 +/- 7.3 years, 50 women) were selected from
      the Osteoarthritis Initiative and matched to controls without radiographic
      chondrocalcinosis (n = 90). Visualization of calcium-containing crystals (CaC)
      was compared between 3D T1-weighted gradient-echo (T1GE), 3D dual echo steady
      state (DESS), 2D intermediate-weighted (IW), and proton density (PD)-weighted
      fast spin-echo (FSE) sequences obtained with 3T MRI and correlated with a
      semiquantitative CaC score obtained from radiographs. Structural abnormalities
      were assessed using Whole-Organ MRI Score (WORMS) and logistic regression models
      were used to compare cartilage compartments with and without CaC. RESULTS:
      Correlations between CaC counts of MRI sequences and degree of radiographic
      calcifications were highest for GE (rT1GE = 0.73, P < 0.001; rDESS = 0.68, P <
      0.001) compared to other sequences (P > 0.05). Meniscus WORMS was significantly
      higher in subjects with chondrocalcinosis compared to controls (P = 0.005).
      Cartilage defects were significantly more frequent in compartments with CaC than
      without (patella: P = 0.006; lateral tibia: P < 0.001; lateral femur condyle: P =
      0.017). CONCLUSIONS: Gradient-echo sequences were most useful for the detection
      of chondrocalcinosis and presence of CaC was associated with higher prevalence of
      cartilage and meniscal damage. KEY POINTS: * Magnetic resonance imaging is useful
      for assessing burden of calcium-containing crystals (CaC). * Gradient-echo
      sequences are superior to fast spin echo sequences for CaC imaging. * Presence of
      CaC is associated with meniscus and cartilage degradation.

PMID- 27704200
TI  - Prominent cerebral veins on susceptibility-weighted imaging (SWI) in pulmonary
      embolism.
AB  - OBJECTIVES: Clinical applications of susceptibility-weighted imaging (SWI) are
      increasing steadily. The aim of this study is to investigate the appearance of
      cerebral veins on SWI, which is very sensitive to the deoxyhaemoglobin level in
      vessels, in pulmonary embolism (PE). METHODS: The cranial SWI images of 19
      patients with PE and 22 controls from September 2013 through March 2016 were
      retrospectively examined for the presence of prominent cerebral veins. MRI
      findings were correlated with blood oxygen levels. RESULTS: 12 of 19 patients
      with PE had hypoxemia and SWI images of 11 of these hypoxemic patients depicted
      prominent cerebral veins in the form of increased number, diameter, and
      elongation. The mean PaO2 and SaO2 in these patients were 48.5 +/- 9.1 mmHg and
      75.2 +/- 8.0 %, respectively. There was a significant correlation between the
      presence of prominent veins on SWI and hypoxemia (p < 0.05). Of the 7 patients
      with normal blood oxygen pressure and saturation, 1 also showed an augmented
      appearance of cerebral veins on SWI. CONCLUSIONS: In the presence of neurological
      symptoms suggestive of an intracranial pathology in patients with PE, a SWI added
      to the conventional MRI sequences may predict hypoxemia and exclude other
      intracranial pathologies. KEY POINTS: * Patients with PE may exhibit nonspecific
      symptoms suggestive of an intracranial pathology. * A cerebral venous prominence
      on SWI should raise the suspicion of hypoxia. * SWI-mIP images intensify the
      appearance of veins and help distinguish other hypointensities.

PMID- 27704201
TI  - Technical feasibility and tissue reaction after silicone-covered biodegradable
      magnesium stent insertion in the oesophagus: a primary study in vitro and in
      vivo.
AB  - OBJECTIVES: Determine the feasibility of and tissue response to biodegradable
      magnesium-silicone stent insertion into the oesophagus of rabbits. METHODS:
      Mechanical compression-recovery and degradation behaviours of the stents were
      investigated in vitro. Thirty rabbits were randomly divided into a magnesium
      silicone stent group (n = 15) that received stent insertion into the lower 1/3 of
      the oesophagus under fluoroscopic guidance and a control group (n = 15).
      Oesophagography was performed at 1, 2 and 4 weeks. Five rabbits in each group
      were euthanized at each time point for histological examination. RESULTS:
      Magnesium-silicone stents showed good flexibility and elasticity, and degraded
      more slowly than bare stents at pH 4.0 and 7.4. All stent insertions were well
      tolerated. The oesophageal diameters at 1, 2 and 4 weeks were 9.7 +/- 0.7, 9.6 +/
      0.8 and 9.6 +/- 0.5 mm, respectively (vs. 9.2 +/- 0.8 mm before intervention; P
      > 0.05). Stent migration occurred in six rabbits (one at 1 week, one at 2 and
      four at 4). Microscopy demonstrated dilation of the oesophageal wall within 1
      week of insertion. Oesophageal injury and collagen deposition following stent
      insertion were similar to control (P > 0.05). CONCLUSIONS: Oesophageal magnesium
      silicone stent insertion was feasible and provided reliable support for 2 weeks
      without causing oesophageal injury or collagen deposition. KEY POINTS: * Mg stent
      provided apparently adequate radial force and silicone membrane reduced magnesium
      biodegradation * Stent insertion provided good support for at least 2 weeks
      before biodegradation * Stenting effectively resulted in oesophageal wall
      remodelling, without demonstrable injury.

PMID- 27704202
TI  - Female urethral stricture: a contemporary series.
AB  - PURPOSE: To report the etiology, presenting symptoms and outcomes of the
      different treatments performed in female patients with recurrent urethral
      stricture. MATERIALS AND METHODS: Twenty-six patients with refractory LUTS were
      diagnosed with a urethral stricture. The symptoms, the treatment performed and
      the outcomes were prospectively recorded. Sixteen patients were treated with a
      urethroplasty using a buccal mucosal graft (BMG) in 14 cases (54 %) and a vaginal
      flap in 2 (8 %). Urethral dilatation, optical urethrotomy and meatoplasty were
      performed in 8 (31 %), 1 (3.8 %) and 1 (3.8 %) patients, respectively. RESULTS:
      Strictures were idiopathic in 11 patients (42 %). Previous urethral
      instrumentation and traumatic vaginal delivery were the commonest causes of
      urethral stricture (42 and 15 %, respectively). The most frequent symptoms were
      reduced flow (93 %), detrusor overactivity (50 %) and UTIs (42 %). The stricture
      was cured in 93 % of patients treated with a BMG urethroplasty and in all the
      patients in which a vaginal flap urethroplasty was performed. In the same group,
      the improvement in urethral pain was observed in the 67 and the 88 % of patients
      were cured from recurrent UTIs. All the patients treated with urethral dilatation
      needed further dilatations; hence, the cure of the stricture was achieved in none
      of them. Improvement in urethral pain, UTIs and detrusor activity was not
      recorded in the latter group. CONCLUSION: Urethroplasty in its various forms has
      demonstrated in the present series the highest cure rate for the treatment of
      recurrent urethral stricture.

PMID- 27704203
TI  - Ileal pouch-anal anastomosis for ulcerative colitis: a Canadian institution's
      experience.
AB  - BACKGROUND: We aimed to summarize the outcomes of ulcerative colitis (UC)
      patients receiving an ileal pouch-anal anastamosis (IPAA) over an 11-year period
      at a high-volume Canadian inflammatory bowel disease (IBD) center. METHODS: A
      retrospective chart review was performed for subjects with UC who underwent IPAA
      between 2002 and 2013. Patient charts were reviewed for demographic data,
      clinical characteristics, preoperative medical treatment, and surgical outcomes.
      Univariate and multivariate logistic regression modeling were used to determine
      significant factors in postoperative outcomes. RESULTS: Seven hundred fifty-eight
      were included from the IBD database. The median age at the time of surgery was
      37.1 (+/-12.1). Mean preoperative disease duration was 8.1 years (+/-8.7). Three
      hundred sixty-nine patients (48.7 %) had systemic corticosteroids (>15 mg/day)
      within 30 days prior to surgery. Of these, 286 patients had high dose (>30
      mg/day) corticosteroids within 7 days of their first surgery. One hundred nine
      (14.0 %) IPAA procedures were performed laparoscopically. Pelvic pouches were
      created in traditional 2 (n = 460) and 3 (n = 285) stages; the remainder (n = 13)
      was performed in non-traditional staged operations. Early complications, defined
      as occurring within the same stay in hospital, consisted of pelvic abscess (n =
      135, 17.8 %), small bowel obstruction (n = 134, 17.7 %), wound infection (n =
      108, 14.3 %), and deep vein thrombosis (n = 33, 4.4 %). The overall pouch leak
      rate was 92 (12.1 %). There was one death in our study. The median length of stay
      was 10.3 days (SD6.0). Late complications, defined as occurring after discharge
      from hospital, consisted of anal stricture (n = 55, 7.3 %), pouch fistula (n =
      26, 3.4 %), and functional pouch failure (n = 7, 0.9 %). CONCLUSIONS: IPAA has
      been found to be a safe and effective method of surgical management of UC
      patients in a high-volume IBD center.

PMID- 27704204
TI  - Fixation techniques and stem dimensions in hinged total knee arthroplasty: a
      finite element study.
AB  - INTRODUCTION: No evidence-based guidelines are available to determine the
      appropriate stem length, and whether or not to cement stems in revision total
      knee arthroplasty (TKA). Therefore, the objective of this study was to compare
      stresses and relative movement of cemented and uncemented stems of different
      lengths using a finite element analysis. MATERIALS AND METHODS: A finite element
      model was created for a synthetic tibia. Two stem lengths (95 and 160 mm) and two
      types of fixation (cemented or press fit) of a hinged TKA were examined. The
      average compressive stress distribution in different regions of interest, as well
      as implant micromotions, was determined and compared during lunge and squat motor
      tasks. RESULTS: Both long and short stems in revision TKA lead to high stresses,
      primarily in the region around the stem tip. The presence of cement reduces the
      stresses in the bone in every region along the stem. Short stem configurations
      are less affected by the presence of cement than the long stem configuration.
      Press-fit stems showed higher micromotions compared to cemented stems.
      CONCLUSIONS: Lowest stresses and micromotion were found for long cemented stems.
      Cementless stems showed more micromotion and increased stress levels especially
      at the level of the stem tip, which may explain the clinical phenomenon of stem
      end pain following revision knee arthroplasty. These findings will help the
      surgeon with optimal individual implant choice.

PMID- 27704205
TI  - Complete prevention of radiation-induced dermatitis using topical adrenergic
      vasoconstrictors.
AB  - Radiation dermatitis is a commonly occurring, painful, side effect of cancer
      radiotherapy that causes some patients to withdraw from the radiotherapy course.
      Our goal was to test and optimize topical application of an adrenergic
      vasoconstrictor to rat skin in a preclinical test to prevent radiation-induced
      dermatitis. A radiation dermatitis assay was developed in which 17.2 Gy to a 1.5
      * 3.0 cm rectangle on the clipped dorsal back of rats yielded Grade 3 radiation
      dermatitis over the irradiated area 13 days later. Single, topical applications
      of each of three adrenergic vasoconstrictors, epinephrine, norepinephrine, or
      phenylephrine, in various vehicle formulations, doses, and application schedules,
      were tested to determine their efficacy in preventing radiation dermatitis. Each
      of the three adrenergic agonists conferred 100 % prevention of radiation
      dermatitis in linear, dose-dependent manners and their EC50 potencies in
      preventing radiation dermatitis correlated well with their individual K d
      association constants for binding to mammalian alpha-adrenergic receptors.
      Topical vasoconstrictor application as little as 3-12 min before irradiation gave
      80-100 % prevention, respectively, of radiation dermatitis. There was a strong
      correlation between the extent (0-100 %) of skin blanch present in skin
      immediately before irradiation and prevention of radiation dermatitis scored 13
      days after irradiation. The data presented here demonstrate that topical
      application of adrenergic vasoconstrictors to rat skin before a large, 17.2 Gy,
      radiation insult confers 100 % protection against radiation dermatitis and
      support ongoing clinical trials and commercial development of a vasoconstrictor
      based product to prevent radiotherapy-induced dermatitis.

PMID- 27704206
TI  - Effect of teriflunomide on QuantiFERON-TB Gold results.
AB  - Multiple sclerosis is a chronic inflammatory disease of the central nervous
      system characterized by damage to myelin and axons, over time leading to
      progressive neuronal degeneration and microglial activation. There is still no
      curative treatment, but during the last 20 years eight different therapies have
      become available including interferon beta, glatiramer acetate, teriflunomide,
      dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and
      teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an
      inhibitory effect on T cell activation in central nervous system of the patients
      with multiple sclerosis. We determined whether teriflunomide affect the
      production of interferon-gamma, interleukin-2 and tumor-necrosis-factor-alpha in
      the QuantiFERON-TB in-Tube-assay. Blood from 24 adults with latent tuberculosis
      infection was added to one standard set of QuantiFERON tubes and one further set
      containing teriflunomide. Teriflunomide resulted in a change in QuantiFERON
      results from positive to negative in four patients with a marked reduction in
      interferon-gamma. Our data indicated that results from QuantiFERON in patients on
      teriflunomide therapy should be interpreted with caution.

PMID- 27704207
TI  - Effects of prebiotics on immune system and cytokine expression.
AB  - Nowadays, use of prebiotics as feed and food additives has received increasing
      interest because of the beneficial effects of prebiotics on the health of animals
      and humans. One of the beneficial effects of prebiotics is stimulation of immune
      system, which can be direct or indirect through increasing population of
      beneficial microbes or probiotics, especially lactic acid bacteria and
      bifidobacteria, in the gut. An important mechanism of action of probiotics and
      prebiotics, by which they can affect the immune system, is changing the
      expression of cytokines. The present review tried to summarize the findings of
      studies that investigated the effects of prebiotics on immune system with
      focusing on their effects on cytokine expression. Generally, most of reviewed
      studies indicated beneficial effects for prebiotics in terms of improving immune
      system, by increasing the expression of anti-inflammatory cytokines, while
      reducing the expressions of proinflammatory cytokines. However, most of studies
      mainly considered the indirect effects of prebiotics on the immune system
      (through changing the composition and population of gut microbiota), and their
      direct effects still need to be further studied using prebiotics with different
      degree of polymerization in different hosts.

PMID- 27704209
TI  - ?

PMID- 27704208
TI  - Improvement in functional performance with high-speed power training in older
      adults is optimized in those with the highest training velocity.
AB  - PURPOSE: To identify whether variability in limb movement velocity during high
      speed power training (HSPT) may impact physical functioning in older adults.
      METHODS: 42 older men and women (71.3 +/- 6.6 years) were randomized to lower
      extremity HSPT (n = 28) or control (CON; n = 14) (Analysis 1) for 12 weeks. A
      second analysis (Analysis 2) allocated HSPT into high-velocity (n = 14) or low
      velocity (n = 14) based on a limb movement speed above or below the median
      average velocity during the 12-week HSPT intervention. Habitual gait speed,
      maximal gait speed, timed up-and-go, and the short physical performance battery
      were measured at baseline and 12 weeks. Change scores were compared between HSPT
      and CON (Analysis 1), and high-velocity, low-velocity, and CON (Analysis 2) using
      ANCOVA. Statistical significance was accepted at p < 0.05. RESULTS: Analysis 1
      There were no group differences in habitual gait speed, maximal gait speed, or
      timed up-and-go between HSPT and CON (all p > 0.05). Short physical performance
      battery was greater in HSPT (0.96 +/- 0.19) compared to CON (0.10 +/- 0.26; p =
      0.01). Analysis 2 There were no group differences in the change in habitual GS (p
      = 0.33) among high-velocity, low-velocity and CON. There were significant group
      differences in the change in maximal GS (p = 0.007), timed up-and-go (p = 0.03),
      and short physical performance battery (p = 0.03). CONCLUSIONS: There is
      considerable variation in self-selected maximal limb velocity during HSPT in
      older adults. In the present cohort, an average limb velocity of 0.88 m/s during
      HSPT was necessary to ensure optimal improvement in functional performance for
      older adults, but this threshold will need further investigation.

PMID- 27704210
TI  - Fat tissues, the brite and the dark sides.
AB  - Fat tissue is well known for its capacity to store energy and its detrimental
      role in obesity and metaflammation. However, humans possess different types of
      fat that have different functions in physiology and metabolic diseases. Apart
      from white adipose tissue (WAT), the body's main energy storage, there is also
      brown adipose tissue (BAT) that dissipates energy as a defense against cold and
      maintains energy balance for the whole body. BAT is present not only in newborns
      but also in adult humans and its mass correlates with leanness. Moreover, "brown
      like" adipocytes have been detected in human WAT. These "brown-in-white" (brite)
      or beige cells can be induced by cold and a broad spectrum of pharmacological
      substances and, therefore, they are also known as "inducible brown adipocytes."
      Activation of brown and/or brite adipocytes reduces metabolic diseases, at least
      in murine models of obesity. Thus, brown/brite adipocytes represent the "brite"
      side of fat and are potential targets for novel therapeutic approaches for
      treatment of obesity and obesity-associated diseases.

PMID- 27704211
TI  - Deep tissue imaging: a review from a preclinical cancer research perspective.
AB  - This review delves into the rapidly evolving field of deep tissue imaging at
      cellular resolution, reviewing popular tissue clearing and staining methods in
      combination with light-sheet fluorescence microscopy (LSFM) including
      quantification and three-dimensional visualization tools, the field of
      applications and perspective, particularly with the focus on preclinical cancer
      research and drug development. The LSFM technique presented here allows an
      extremely fast optical sectioning for three-dimensional reconstruction of
      centimeter-sized tissue samples at cellular resolution. However, optical clearing
      methods are required to receive optical transparent tissue. Application of either
      tissue autofluorescence, in vivo fluorescence labeling, endogenous fluorescence
      or ex vivo whole-mount immunolabeling enables three-dimensional in situ
      visualization of morphological and functional features of unsectioned whole-mount
      tissue samples. This powerful and innovative imaging technique opens up a new
      dimension of tissue analysis providing detailed and comprehensive insights into
      biology. It enables the investigation of normal and pathological tissue features
      and disease progression and allows precise monitoring of potential therapeutic
      interventions in intact biological tissue on a cellular level.

PMID- 27704212
TI  - High mobility group box 1 (HMGB1): dual functions in the cochlear auditory
      neurons in response to stress?
AB  - High mobility group box 1 (HMGB1) is a DNA-binding protein that facilitates gene
      transcription and may act extracellularly as a late mediator of inflammation. The
      roles of HMGB1 in the pathogenesis of the spiral ganglion neurons (SGNs) of the
      cochlea are currently unknown. In the present study, we tested the hypothesis
      that early phenotypical changes in the SGNs of the amikacin-poisoned rat cochlea
      are mediated by HMGB1. Our results showed that a marked downregulation of HMGB1
      had occurred by completion of amikacin treatment, coinciding with acute damage at
      the dendrite extremities of the SGNs. A few days later, during the recovery of
      the SGN dendrites, the protein was re-expressed and transiently accumulated
      within the nuclei of the SGNs. The phosphorylated form of the transcription
      factor c-Jun (p-c-Jun) was concomitantly detected in the nuclei of the SGNs where
      it often co-localized with HMGB1, while the anti-apoptotic protein BCL2 was over
      expressed in the cytoplasm. In animals co-treated with amikacin and the histone
      deacetylase inhibitor trichostatin A, both HMGB1 and p-c-Jun were exclusively
      found within the cytoplasm. The initial disappearance of HMGB1 from the affected
      SGNs may be due to its release into the external medium, where it may have a
      cytokine-like function. Once re-expressed and translocated into the nucleus,
      HMGB1 may facilitate the transcriptional activity of p-c-Jun, which in turn may
      promote repair mechanisms. Our study therefore suggests that HMGB1 can positively
      influence the survival of SGNs following ototoxic exposure via both its
      extracellular and intranuclear functions.

PMID- 27704214
TI  - Management of bone fragments in nonmissile compound depressed skull fractures.
AB  - BACKGROUND: There is no settled standard of care or even a consensus between
      neurosurgeons on the replacement of bone fragments in compound depressed skull
      fractures (CDSF). MATERIALS AND METHODS: This cohort study retrospectively
      reviewed the patients with nonmissile CDSF who were admitted to our university
      hospitals from January 2010 to January 2015. Patients who were managed
      nonoperatively, polytrauma, comatose patients, and CDSF over the air sinuses were
      excluded from this study. RESULTS: This study includes 87 consecutive patients
      with nonmissile CDSF who were surgically treated from January 2010 to January
      2015. Follow-up varied from 12 to 36 months. All of the 87 patients presented
      within 1 week after injury; 76 patients (87.35 %) had surgery within the first 72
      h of trauma, and these patients had primary bone fragment replacement (after
      decontamination) with or without miniplates and minimesh. The patients who
      presented after 72 h of trauma with no wound discharge had their bone fragments
      autoclaved then replaced. The patients who presented after 72 h of trauma and had
      pus or serous discharge from the wound had their bone fragments discarded and
      scheduled for delayed cranioplasty. The long-term infection rate in all patients
      who had a primary bone fragment replacement in this study is 0 %. CONCLUSIONS:
      Primary bone fragment replacement (after decontamination) is a safe option in the
      management of nonmissile CDSF within 72 h of trauma in selected patients.

PMID- 27704213
TI  - Network analysis of mitonuclear GWAS reveals functional networks and tissue
      expression profiles of disease-associated genes.
AB  - While mitochondria have been linked to many human diseases through genetic
      association and functional studies, the precise role of mitochondria in specific
      pathologies, such as cardiovascular, neurodegenerative, and metabolic diseases,
      is often unclear. Here, we take advantage of the catalog of human genome-wide
      associations, whole-genome tissue expression and expression quantitative trait
      loci datasets, and annotated mitochondrial proteome databases to examine the role
      of common genetic variation in mitonuclear genes in human disease. Through
      pathway-based analysis we identified distinct functional pathways and tissue
      expression profiles associated with each of the major human diseases. Among our
      most striking findings, we observe that mitonuclear genes associated with cancer
      are broadly expressed among human tissues and largely represent one functional
      process, intrinsic apoptosis, while mitonuclear genes associated with other
      diseases, such as neurodegenerative and metabolic diseases, show tissue-specific
      expression profiles and are associated with unique functional pathways. These
      results provide new insight into human diseases using unbiased genome-wide
      approaches.

PMID- 27704215
TI  - Natural occurrence of NS5B inhibitor resistance-associated variants in Brazilian
      patients infected with HCV or HCV and HIV.
AB  - Resistance-associated variants (RAVs) represent a challenge to the success of new
      HCV therapies. The aim of this study was to describe the prevalence of naturally
      occurring NS5B RAVs in Brazilian direct acting antivirals (DAA)-naive patients
      infected with HCV genotype 1, or co-infected with HIV. Patient enrollment and
      sample collection were performed between 2011 and 2013. Using Sanger-based
      sequencing, 244 sequences were obtained. RAVs detected in HCV-1a sequences were
      V321A (1.6 %), M414V (1.3 %), A421V (21.4-23.7 %), A421G (1.3 %) and Y448H (1.3
      %); and in HCV-1b sequences were L159F (16.1 %), C316N (7.1-16.3 %) and A421V
      (3.2-6.3 %). Understanding the real RAVs scenario in patients is fundamental to
      establishing the most effective therapeutic strategy and in minimizing the risks
      for their selection.

PMID- 27704216
TI  - Heat-stressed Metarhizium anisopliae: viability (in vitro) and virulence (in
      vivo) assessments against the tick Rhipicephalus sanguineus.
AB  - The current study investigated the thermotolerance of Metarhizium anisopliae s.l.
      conidia from the commercial products Metarril(r) SP Organic and Metarril(r) WP.
      The efficacy of these M. anisopliae formulations against the tick Rhipicephalus
      sanguineus s.l. was studied in laboratory under optimum or heat-stress
      conditions. The products were prepared in water [Tween(r) 80, 0.01 % (v/v)] or
      pure mineral oil. Conidia from Metarril(r) SP Organic suspended in water
      presented markedly delayed germination after heating to constant 40  degrees C
      (for 2, 4, or 6 h) compared to conidia suspended in mineral oil. Metarril(r) SP
      Organic suspended in oil and exposed to daily cycles of heat-stress (40  degrees
      C for 4 h and 25  degrees C for 19 h for 5 consecutive days) presented relative
      germination of conidia ranging from 92.8 to 87.2 % from day 1 to day 5,
      respectively. Conversely, germination of conidia prepared in water ranged from
      79.3 to 39.1 % from day 1 to day 5, respectively. Culturability of Metarril(r) WP
      decreased from 96 % when conidia were cultured for 30 min prior to heat exposure
      (40  degrees C for 4 h) to 9 % when conidia were cultured for 8 h. Tick percent
      control was distinctly higher when engorged females were treated with oil
      suspensions rather than water suspensions, even when treated ticks were exposed
      to heat-stress regimen. Oil-based applications protected fungal conidia against
      heat-stress. Although Metarril(r) is not registered for tick control, it may be
      useful for controlling R. sanguineus, especially if it is prepared in mineral
      oil.

PMID- 27704217
TI  - Henneguya laseeae n. sp. from flathead catfish (Pylodictis olivaris) in the upper
      Mississippi River.
AB  - A novel species of Henneguya was isolated from flathead catfish (Pylodictis
      olivaris) captured in the upper Mississippi River near Lansing (Allamakee
      County), IA, and La Crosse (La Crosse County), WI. Designated Henneguya laseeae
      n. sp., this novel species is described using critical morphological features,
      histology, and 18S ribosomal RNA gene sequence. Ovoid cysts, ranging from 1200 to
      1800 MUm in width, tended to be at filament tips or in the distal third, often
      directly on the filament midline, but occasionally paramedian. Lanceolate-shaped
      myxospores were consistent with those of the genus Henneguya. The spore body was
      16.2 +/- 0.5 MUm (mean +/- standard deviation; range = 15.1-17.0 MUm) in length,
      6.0 +/- 0.4 MUm (5.1-6.6 MUm) in width, and 4.7 +/- 0.2 MUm (4.4-4.9 MUm) thick.
      The two polar capsules at the anterior of the spore body were 5.9 +/- 0.3 MUm
      (5.3-6.3 MUm) in length and 1.8 +/- 0.1 MUm (1.6-2.1 MUm) in width and contained
      six to seven turns in the polar filament. The caudal processes tapered to fine
      points and were 54.3 +/- 2.9 MUm (49.1-61.7 MUm) in length. Total spore length
      was 70.4 +/- 3.3 MUm (64.5-79.4 MUm). The spores and plasmodium of this species
      are of similar size and morphology to other species of Henneguya from ictalurid
      fishes. Additionally, the 18S rRNA gene sequences placed this isolate within a
      clade populated by Henneguya spp. from North American ictalurids. This is the
      first reported species of Henneguya from flathead catfish.

PMID- 27704218
TI  - Direct and indirect parieto-medial temporal pathways for spatial navigation in
      humans: evidence from resting-state functional connectivity.
AB  - Anatomical and functional findings in primates suggest the existence of a
      dedicated parieto-medial temporal pathway for spatial navigation, consisting of
      both direct and indirect projections from the caudal inferior parietal lobe
      (cIPL) to the hippocampus and the parahippocampal cortex, with indirect
      projections relaying through the posterior cingulate and retrosplenial cortex.
      This neural network is largely unexplored in humans. This study aimed at testing
      the existence of a parieto-medial temporal pathway for spatial navigation in
      humans. We explored the cortical connectivity patterns of the parahippocampal
      place area (PPA), the retrosplenial cortex (RSC), and the hippocampus (HC) using
      resting-state functional connectivity MRI. Our results demonstrate the existence
      of connections between the medial temporal lobe structures, i.e., PPA and HC, and
      the angular gyrus (AG), the human homologue of cIPL, as well as between RSC and
      AG. These connectivity patterns seem to reflect the direct and the indirect
      projections found in primates from cIPL to the medial temporal lobe. Such a
      result deserves feasible considerations to better understand the brain networks
      underpinning human spatial navigation.

PMID- 27704220
TI  - A review of the safety of clozapine during pregnancy and lactation.
AB  - Clozapine is an antipsychotic used in the management of treatment-resistant
      schizophrenia. However, little is known about clozapine use during pregnancy and
      lactation, or its impact on the mother, foetus, and infant. This review aims to
      summarize the available literature on the safety of clozapine use during the
      perinatal period. EMBASE, PsycINFO, and MEDLINE were searched from their
      inceptions through June 2016. The review encompasses 21 studies that have
      examined clozapine use during pregnancy and lactation. The limited available data
      do not support an increased risk of congenital malformations in foetuses exposed
      to clozapine during pregnancy, though rates of gestational diabetes are twice as
      high in pregnant women using clozapine. Clozapine accumulation in foetal serum
      possibly contributes to increased rates of floppy infant syndrome at delivery,
      decreased foetal heart rate variability, and seizures in infancy. Clozapine
      crosses the placenta and also accumulates in breast milk, which may increase the
      risk of agranulocytosis in infants and may necessitate infant testing. The
      majority of these data come from case reports and case series, making it unclear
      if the published risks associated with clozapine are due to mental illness,
      lifestyle factors, or co-treatment with other psychotropic medications. While the
      available literature on clozapine use during the perinatal period is very
      limited, the risks of clozapine use during pregnancy and the postpartum period
      should be discussed with women and weighed against those associated with other
      treatments and partially or untreated schizophrenia.

PMID- 27704221
TI  - Insights into the spontaneity of hydrogen bond formation between formic acid and
      phthalimide derivatives.
AB  - We evaluated a group of phthalimide derivatives, which comprise a convenient test
      set for the study of the multiple factors involved in the energetics of hydrogen
      bond formation. Accordingly, we carried out quantum chemical calculations on the
      hydrogen bonded complexes formed between a sample of phthalimide derivatives with
      formic acid with the intent of identifying the most important electronic and
      structural factors related to how their strength and spontaneity vary across the
      series. The geometries of all species considered were fully optimized at DFT
      B3LYP/6-31++G(d,p), RM1, RM1-DH2, and RM1-D3H4 level, followed by frequency
      calculations to determine their Gibbs free energies of hydrogen bond formation
      using Gaussian 2009 and MOPAC 2012. Our results indicate that the phthalimide
      derivatives that form hydrogen bond complexes most favorably, have in their
      structures only one C=O group and at least one NH group. On the other hand, the
      phthalimide derivatives predicted to form hydrogen bonds least favorably, possess
      in their structures two carbonyl groups, C=O, and no NH group. The ability to
      donate electrons and simultaneously receive one acidic hydrogen is the most
      important property related to the spontaneity of hydrogen bond formation. We
      further chose two cyclic compounds, phthalimide and isoindolin-1-one, in which to
      study the main changes in molecular, structural and spectroscopic properties as
      related to the formation of hydrogen bonds. Thus, the greatest ability of the
      isoindolin-1-one compound in forming hydrogen bonds is evidenced by the larger
      effect on the structural, vibrational, and chemical shifts properties associated
      with the O-H group. In summary, the electron-donating ability of the hydrogen
      bond acceptor emerged as the most important property differentiating the
      spontaneity of hydrogen bond formation in this group of complexes.

PMID- 27704219
TI  - Abundant collateralization of temporal lobe projections to the accumbens, bed
      nucleus of stria terminalis, central amygdala and lateral septum.
AB  - Behavioral flexibility is subserved in part by outputs from the cerebral cortex
      to telencephalic subcortical structures. In our earlier evaluation of the
      organization of the cortical-subcortical output system (Reynolds and Zahm, J
      Neurosci 25:11757-11767, 2005), retrograde double-labeling was evaluated in the
      prefrontal cortex following tracer injections into pairs of the following
      subcortical telencephalic structures: caudate-putamen, core and shell of the
      accumbens (Acb), bed nucleus of stria terminalis (BST) and central nucleus of the
      amygdala (CeA). The present study was done to assess patterns of retrograde
      labeling in the temporal lobe after similar paired tracer injections into most of
      the same telencephalic structures plus the lateral septum (LS). In contrast to
      the modest double-labeling observed in the prefrontal cortex in the previous
      study, up to 60-80 % of neurons in the basal and accessory basal amygdaloid
      nuclei and amygdalopiriform transition area exhibited double-labeling in the
      present study. The most abundant double-labeling was generated by paired
      injections into structures affiliated with the extended amygdala, including the
      CeA, BST and Acb shell. Injections pairing the Acb core with the BST or CeA
      produced significantly fewer double-labeled neurons. The ventral subiculum
      exhibited modest amounts of double-labeling associated with paired injections
      into the Acb, BST, CeA and LS. The results raise the issue of how an
      extraordinarily collateralized output from the temporal lobe may contribute to
      behavioral flexibility.

PMID- 27704224
TI  - Genomic Selection Using Extreme Phenotypes and Pre-Selection of SNPs in Large
      Yellow Croaker (Larimichthys crocea).
AB  - Genomic selection (GS) is an effective method to improve predictive accuracies of
      genetic values. However, high cost in genotyping will limit the application of
      this technology in some species. Therefore, it is necessary to find some methods
      to reduce the genotyping costs in genomic selection. Large yellow croaker is one
      of the most commercially important marine fish species in southeast China and
      Eastern Asia. In this study, genotyping-by-sequencing was used to construct the
      libraries for the NGS sequencing and find 29,748 SNPs in the genome. Two traits,
      eviscerated weight (EW) and the ratio between eviscerated weight and whole body
      weight (REW), were chosen to study. Two strategies to reduce the costs were
      proposed as follows: selecting extreme phenotypes (EP) for genotyping in
      reference population or pre-selecting SNPs to construct low-density marker panels
      in candidates. Three methods of pre-selection of SNPs, i.e., pre-selecting SNPs
      by absolute effects (SE), by single marker analysis (SMA), and by fixed intervals
      of sequence number (EL), were studied. The results showed that using EP was a
      feasible method to save the genotyping costs in reference population.
      Heritability did not seem to have obvious influences on the predictive abilities
      estimated by EP. Using SMA was the most feasible method to save the genotyping
      costs in candidates. In addition, the combination of EP and SMA in genomic
      selection also showed good results, especially for trait of REW. We also
      described how to apply the new methods in genomic selection and compared the
      genotyping costs before and after using the new methods. Our study may not only
      offer a reference for aquatic genomic breeding but also offer a reference for
      genomic prediction in other species including livestock and plants, etc.

PMID- 27704223
TI  - Gene Co-Expression Network Analysis Reveals the Correlation Patterns Among Genes
      in Euryhaline Adaptation of Crassostrea gigas.
AB  - The Pacific oyster Crassostrea gigas is a dominant aquaculture species in many
      intertidal zones throughout the Pacific and Atlantic Oceans and can tolerate a
      wide range of salinity. Studying the gene expression profiles of oyster gills had
      found differentially expressed genes (DEGs) involved in salinity tolerance. A
      systematic study of cellular response to salinity stress may provide insights
      into the mechanism of acquired salinity tolerance. Here, weighted gene co
      expression network analysis (WGCNA) was carried out using RNA-seq data from gill
      transcriptome in response to different salinity. A total of 25,463 genes were
      parsed into 22 gene modules, of which 5 gene modules were identified as salinity
      related modules. Brown module was the only one significantly correlated with
      salinity and free amino acids (FAAs) contents, which was associated with cellular
      metabolism, biosynthesis of amino acids, oxidation reduction, electron transport,
      nitrogen compound metabolism, and others. The enriched pathways in brown module
      were mainly about FAAs metabolism. The other four modules were significantly
      correlated with certain FAAs, and were over-represented in certain salinity.
      These results indicated that C. gigas triggered different FAAs in different
      salinity stress. This study represents the first RNA-seq gene network analysis in
      oysters responding to different salinity stresses. These results provide a
      systems-level framework to help understand the complexity of cellular process in
      response to osmotic stress and show the function and regulated genes of different
      FAAs at the molecular level.

PMID- 27704222
TI  - Distinct differences in metal ion specificity of RNA and DNA G-quadruplexes.
AB  - RNA G-quadruplexes, as their well-studied DNA analogs, require the presence of
      cations to fold and remain stable. This is the first comprehensive study on the
      interaction of RNA quadruplexes with metal ions. We investigated the formation
      and stability of two highly conserved and biologically relevant RNA quadruplex
      forming sequences (24nt-TERRA and 18nt-NRAS) in the presence of several
      monovalent and divalent metal ions, namely Li+, Na+, K+, Rb+, Cs+, NH4+, Mg2+,
      Ca2+, Sr2+, and Ba2+. Circular dichroism was used to probe the influence of these
      metal ions on the folded fraction of the parallel G-quadruplexes, and UV thermal
      melting experiments allowed to assess the relative stability of the structures in
      each cationic condition. Our results show that the RNA quadruplexes are more
      stable than their DNA counterparts under the same buffer conditions. We have
      observed that the addition of mainly Na+, K+, Rb+, NH4+, as well as Sr2+ and Ba2+
      in water, shifts the equilibrium to the folded quadruplex form, whereby the NRAS
      sequence responds stronger than TERRA. However, only K+ and Sr2+ lead to a
      significant increase in the stability of the folded structures, which is
      consistent with their coordination to the O6 atoms from the G-quartet guanosines.
      Compared to the respective DNA motives, dNRAS and htelo, the RNA sequences are
      not stabilized by Na+ ions. Finally, the difference in response between NRAS and
      TERRA, as well as to the corresponding DNA sequences with respect to different
      metal ions, could potentially be exploited for selective targeting purposes.

PMID- 27704225
TI  - Updated evidence on endoscopic resection of early gastric cancer from Japan.
AB  - BACKGROUND: Endoscopic resection for early gastric cancer (EGC) plays a central
      role in the treatment of EGC in Japan. However, there is still room for
      improvement, and it is necessary to summarize the recently obtained knowledge
      from Japan for further improvement. METHODS: We conducted a PubMed search to
      select relevant articles in the 5 years until September 18, 2016, using the
      keywords "gastric cancer" and "endoscopic treatment," "endoscopic submucosal
      dissection," "endoscopic mucosal resection," or "polypectomy" and filtering
      article types as "clinical study" or "clinical trial." RESULTS: Among the 329
      articles selected automatically from the keywords "polypectomy" (1 article),
      "endoscopic mucosal resection" (29 articles), "endoscopic submucosal dissection"
      (77 articles), and "endoscopic treatment" (222 articles) in combination with
      "gastric cancer," 32 relevant articles from Japanese investigators were chosen.
      Seven articles were categorized into "equipment," 4 into "preparation and
      sedation," 17 into "complications and their prevention," and 4 into "therapeutic
      outcomes." Among them, CO2 insufflation, propofol sedation, and how to prevent
      post-endoscopic submucosal dissection (ESD) ulcer bleeding and achieve post-ESD
      ulcer healing were intensively investigated. Long-term outcomes of endoscopic
      mucosal resection and ESD were also reported as favorable outcomes. CONCLUSIONS:
      Endoscopic resection for EGC is still developing toward an ideal form, pursuing a
      more reliable, safer, and faster minimally invasive treatment.

PMID- 27704227
TI  - Erratum to: Soft Tissue Phantoms for Realistic Needle Insertion: A Comparative
      Study.

PMID- 27704226
TI  - Impact of neoadjuvant therapy on eligibility for and frequency of breast
      conservation in stage II-III HER2-positive breast cancer: surgical results of
      CALGB 40601 (Alliance).
AB  - OBJECTIVE: It had been previously shown that patients who receive neoadjuvant
      systemic therapy (NST) are more likely to undergo breast-conserving therapy (BCT)
      than those who have primary surgery. However, the frequency with which patients
      who are not BCT-eligible prior to NST convert to BCT-eligible with treatment is
      unknown. To document this conversion rate in a subset of patients expected to
      have a high clinical response rate to NST, we studied surgical assessment and
      management of patients enrolled on a randomized neoadjuvant trial for stage II
      III HER2-positive breast cancer (HER2 + BC)(CALGB 40601). METHODS: The treating
      surgeon assessed BCT candidacy based on clinico-radiographic criteria both before
      and after NST. Definitive breast surgical management was at surgeon and patient
      discretion. We sought to determine (1) the conversion rate from BCT-ineligible to
      BCT-eligible (2) the percentage of BCT-eligible patients who chose breast
      conservation, and (3) the rate of successful BCT. We also evaluated surgeon
      determined factors for BCT-ineligibility and the correlation between BCT
      eligibility and pathologic complete response (pCR). RESULTS: Of 292 patients with
      pre- and post-NST surgical assessments, 59 % were non-BCT candidates at baseline.
      Of the 43 % of these patients who converted with NST, 67 % opted for BCT, with an
      80 % success rate. NST increased the BCT-eligible rate from 41 to 64 %. Common
      factors cited for BCT-ineligibility prior to NST including tumor size (56 %) and
      probable poor cosmetic outcome (26 %) were reduced by 67 and 75 %, respectively,
      with treatment, while multicentricity, the second most common factor (33 %), fell
      by only 16 %. Since 23 % of the BCT-eligible patients chose mastectomy, BCT was
      the final surgical procedure in just 40 % of the patients. Patients considered
      BCT-eligible both at baseline and after NST had a pCR rate of 55 %, while
      patients who were BCT-ineligible prior to NST had the same pCR rate (44 %)
      whether they converted to BCT-eligible or not. CONCLUSIONS: Many patients with
      HER2 + BC deemed ineligible for BCT at baseline can be converted to BCT-eligible
      with NST; excluding patients with multicentric disease substantially increases
      that percentage. In converted patients who opt for BCT, the success rate is
      similar to that of patients considered BCT-eligible at baseline. Whether a BCT
      ineligible patient converts to BCT eligibility or not does not appear to affect
      the likelihood of achieving a pCR. Despite the efficacy of NST in this patient
      cohort, only 40 % of patients had successful BCT; further research into why BCT
      eligible patients often opt for mastectomy is needed.

PMID- 27704228
TI  - Cecal wedge resection appendectomy for the management of appendiceal polyps.

PMID- 27704229
TI  - Automatic construction of subject-specific human airway geometry including
      trifurcations based on a CT-segmented airway skeleton and surface.
AB  - We propose a method to construct three-dimensional airway geometric models based
      on airway skeletons, or centerlines (CLs). Given a CT-segmented airway skeleton
      and surface, the proposed CL-based method automatically constructs subject
      specific models that contain anatomical information regarding branches, include
      bifurcations and trifurcations, and extend from the trachea to terminal
      bronchioles. The resulting model can be anatomically realistic with the
      assistance of an image-based surface; alternatively a model with an idealized
      skeleton and/or branch diameters is also possible. This method systematically
      identifies and classifies trifurcations to successfully construct the models,
      which also provides the number and type of trifurcations for the analysis of the
      airways from an anatomical point of view. We applied this method to 16 normal and
      16 severe asthmatic subjects using their computed tomography images. The average
      distance between the surface of the model and the image-based surface was 11 % of
      the average voxel size of the image. The four most frequent locations of
      trifurcations were the left upper division bronchus, left lower lobar bronchus,
      right upper lobar bronchus, and right intermediate bronchus. The proposed method
      automatically constructed accurate subject-specific three-dimensional airway
      geometric models that contain anatomical information regarding branches using
      airway skeleton, diameters, and image-based surface geometry. The proposed method
      can construct (i) geometry automatically for population-based studies, (ii)
      trifurcations to retain the original airway topology, (iii) geometry that can be
      used for automatic generation of computational fluid dynamics meshes, and (iv)
      geometry based only on a skeleton and diameters for idealized branches.

PMID- 27704231
TI  - Mosaicism: throwing the baby out with the bath water?

PMID- 27704230
TI  - Smoking cessation and long-term weight gain in the Framingham Heart Study: an
      application of the parametric g-formula for a continuous outcome.
AB  - Weight gain after smoking cessation can lessen the health benefits of, and reduce
      the incentives for, quitting smoking. Randomized clinical trials of smoking
      cessation have estimated this weight gain only over short periods of follow-up.
      We provide an estimate of long-term post-cessation weight gain in the Framingham
      Heart Study, a prospective observational study. We identified 2001 smokers free
      of diabetes, cancer, and cardiovascular disease in 1952. Using the parametric g
      formula we estimated mean weight in 1972 if all smokers had quit at baseline
      versus if all had continued smoking. Our estimates were adjusted for demographic,
      socio-economic, and clinical factors at baseline and during follow-up. The
      estimated mean weight (95 % CI) at 20 years if all smokers had quit smoking was
      75.2 kg (73.5, 76.6), compared with 70.2 kg (68.7, 71.8) if they had smoked 20
      cigarettes/day and 73.4 kg (71.9, 74.6) if they had smoked 5 cigarettes/day
      (i.e., an estimated mean weight gain of 5.1 kg (3.1, 6.6) and 1.8 kg (0.8, 2.8),
      respectively). Smokers who were overweight or obese at baseline had a greater
      post-cessation weight gain on average. Our estimates suggest that smoking
      cessation can result in increases in body weight over 20 years. While the
      benefits of smoking cessation outweigh the risks due to post-cessation weight
      gain, our results highlight the need for long-term weight management
      interventions in combination with smoking cessation.

PMID- 27704234
TI  - Estimation of Ground-State and Singlet Excited-State Dipole Moments of
      Substituted Schiff Bases Containing Oxazolidin-2-one Moiety through
      Solvatochromic Methods.
AB  - Absorption and fluorescence studies on novel Schiff bases (E)-4-(4-(4-nitro
      benzylideneamino)benzyl)oxazolidin-2-one (NBOA) and (E)-4-(4-(4-chlorobenzylidene
      amino)benzyl)oxazolidin-2-one (CBOA) were recorded in a series of twelve solvents
      upon increasing polarity at room temperature. Large Stokes shift indicates
      bathochromic fluorescence band for both the molecules. The photoluminescence
      properties of Schiff bases containing electron withdrawing and donating
      substituents were analyzed. Intramolecular charge transfer behavior can be
      studied based on the influence of different substituents in Schiff bases. Changes
      in position and intensity of absorption and fluorescence spectra are responsible
      for the stabilization of singlet excited-states of Schiff base molecules with
      different substituents, in polar solvents. This is attributed to the
      Intramolecular charge transfer (ICT) mechanism. In case of electron donating (
      Cl) substituent, ICT contributes largely to positive solvatochromism when
      compared to electron withdrawing (-NO2) substituent. Ground-state and singlet
      excited-state dipole moments of NBOA and CBOA were calculated experimentally
      using solvent polarity function approaches given by Lippert-Mataga, Bakhshiev,
      Kawskii-Chamma-Viallet and Reichardt. Due to considerable pi- electron density
      redistribution, singlet excited-state dipole moment was found to be greater than
      ground-state dipole moment. Ground-state dipole moment value which was determined
      by quantum chemical method was used to estimate excited-state dipole moment using
      solvatochromic correlations. Kamlet-Abboud-Taft and Catalan multiple linear
      regression approaches were used to study non-specific solute-solvent interaction
      and hydrogen bonding interactions in detail. Optimized geometry and HOMO-LUMO
      energies of NBOA and CBOA have been determined by DFT and TD-DFT/PCM (B3LYP/6
      311G (d, p)). Mulliken charges and molecular electrostatic potential have also
      been evaluated from DFT calculations.

PMID- 27704232
TI  - Activating glutamate decarboxylase activity by removing the autoinhibitory domain
      leads to hyper gamma-aminobutyric acid (GABA) accumulation in tomato fruit.
AB  - KEY MESSAGE: The C-terminal extension region of SlGAD3 is likely involved in
      autoinhibition, and removing this domain increases GABA levels in tomato fruits.
      gamma-Aminobutyric acid (GABA) is a ubiquitous non-protein amino acid with
      several health-promoting benefits. In many plants including tomato, GABA is
      synthesized via decarboxylation of glutamate in a reaction catalyzed by glutamate
      decarboxylase (GAD), which generally contains a C-terminal autoinhibitory domain.
      We previously generated transgenic tomato plants in which tomato GAD3 (SlGAD3)
      was expressed using the 35S promoter/NOS terminator expression cassette (35S
      SlGAD3-NOS), yielding a four- to fivefold increase in GABA levels in red-ripe
      fruits compared to the control. In this study, to further increase GABA
      accumulation in tomato fruits, we expressed SlGAD3 with (SlGAD3 OX ) or without
      (SlGAD3DeltaC OX ) a putative autoinhibitory domain in tomato using the fruit
      ripening-specific E8 promoter and the Arabidopsis heat shock protein 18.2 (HSP)
      terminator. Although the GABA levels in SlGAD3 OX fruits were equivalent to those
      in 35S-SlGAD3-NOS fruits, GABA levels in SlGAD3DeltaC OX fruits increased by 11-
      to 18-fold compared to control plants, indicating that removing the
      autoinhibitory domain increases GABA biosynthesis activity. Furthermore, the
      increased GABA levels were accompanied by a drastic reduction in glutamate and
      aspartate levels, indicating that enhanced GABA biosynthesis affects amino acid
      metabolism in ripe-fruits. Moreover, SlGAD3DeltaC OX fruits exhibited an orange
      ripe phenotype, which was associated with reduced levels of both carotenoid and
      mRNA transcripts of ethylene-responsive carotenogenic genes, suggesting that over
      activation of GAD influences ethylene sensitivity. Our strategy utilizing the E8
      promoter and HSP terminator expression cassette, together with SlGAD3 C-terminal
      deletion, would facilitate the production of tomato fruits with increased GABA
      levels.

PMID- 27704235
TI  - Photoluminescence and Coordination Behaviour of Lanthanide Complexes of Tris
      (Aminomethyl)Ethane-5-Oxine in Aqueous Solution.
AB  - Photophysical properties of a multidentate tripodal ligand, 5,5'-(2-(((8
      hydroxyquinolin-5-yl) methylamino)methyl)-2-methylpropane-1,3-diyl) bis
      (azanediyl)bis (methylene)diquinolin-8-ol, (TAME5OX), with La3+ and Er3+ ions
      have been examined for photonics applications. The change in behavior in
      electronic spectra of these complexes reveals the use of TAME5OX as a sensitive
      optical pH based sensor to detect Ln3+ ions whereas indication of strong green
      fluorescence allows simultaneous sensing within the visible region in competitive
      medium. The intense fluorescence intermittently gets quenched under acidic and
      basic conditions due to photoinduced intramolecular electron transfer from the
      excited 8-hydroxyquinoline (8-HQ) moiety to the metal ion. This renders these
      compounds the OFF-ON-OFF type of pH-dependent fluorescent sensor. The
      thermodynamic stability and coordination behaviour of the chelator with the said
      lanthanide ions have also been probed by potentiometric, UV - visible and
      fluorescence spectrophotometric method. TAME5OX forms protonated complex [Ln
      (H4L)]4+ below pH ~4.0 which sequentially deprotonates through one proton process
      with increase of pH. The stability constants of neutral complexes have been
      determined to be in the range log beta110 = 32-34 and pLn in the range of 14-20,
      indicating TAME5OX is a good synthetic lanthanide chelator. Theoretical spectra
      were also calculated by ZINDO/s methodology at single excitations (CIS) level on
      PM7 as sparkle energy-minimized geometries.

PMID- 27704236
TI  - Neurologic Complications of Common Variable Immunodeficiency.
AB  - Common variable immunodeficiency is a rare disorder of immunity associated with a
      myriad of clinical manifestations including recurrent infections, autoimmunity,
      and malignancy. Though rare, neurologic complications have been described in a
      small number of case reports and case series of CVID patients. In this article,
      we present a patient with CVID who suffered significant neurologic morbidity and
      categorize the reported range of neurologic complications associated with CVID.
      Our case highlights the complex nature of neurologic manifestations in CVID
      patients, and our review of the current database suggests that infection and
      inflammatory neurologic disorders are the cause of most neurologic presentations.

PMID- 27704237
TI  - Rise of the Machines: A Critical Review on the Behavioural Effects of Automating
      Traditional Gambling Games.
AB  - Automated gambling products are now a common feature on many casino floors.
      Despite their increasing prevalence, little research has considered the impact of
      converting games traditionally free from technological enhancements to automated
      versions. This review seeks to illustrate how automation is likely to change the
      way people engage and experience traditional games based around five prominent
      modifications: visual and auditory enhancements; illusions of control; cognitive
      complexity; expedited play; and social customisation. Otherwise known as the
      "VICES" framework. The inclusion of rich graphics, event-dependent sound and game
      play information such as statistics, history, betting options and strategic
      betting are likely to prolong and entice gambling while encouraging more intense
      betting. Changes to the social environment due to the asocial nature of automated
      products is also likely to significantly change the gambling experience. Given
      the increasing prevalence of these products in the marketplace, it is important
      to consider the implications of converting traditional products to automated form
      as technological enhancements have the potential to allow for faster, more
      intense betting. More research is needed to determine the full impact of
      automation on player behaviours in order to understand the potential risks
      associated with technological enhancements to traditional games.

PMID- 27704238
TI  - MY MOTHER, MY STORY.
AB  - This piece returns to the writer's memoir essays about her mother's chronic lung
      disease to examine the relationship between the act of caregiving and the act of
      writing. In arguing for important differences between the clinical, healing
      imperatives of narrative medicine and the primacy for the writer of self
      reflection, personal need and career, the essay demonstrates how writing remains
      in many ways at odds with the obligations and the hopes of caregiving. At the
      same time, the essay argues that writing her mother's stories of illness holds
      the potential for both honor and mutuality-and can, in fact, constitute a form of
      caregiving.

PMID- 27704239
TI  - Objective Bayesian Comparison of Constrained Analysis of Variance Models.
AB  - In the social sciences we are often interested in comparing models specified by
      parametric equality or inequality constraints. For instance, when examining three
      group means [Formula: see text] through an analysis of variance (ANOVA), a model
      may specify that [Formula: see text], while another one may state that [Formula:
      see text], and finally a third model may instead suggest that all means are
      unrestricted. This is a challenging problem, because it involves a combination of
      nonnested models, as well as nested models having the same dimension. We adopt an
      objective Bayesian approach, requiring no prior specification from the user, and
      derive the posterior probability of each model under consideration. Our method is
      based on the intrinsic prior methodology, suitably modified to accommodate
      equality and inequality constraints. Focussing on normal ANOVA models, a
      comparative assessment is carried out through simulation studies. We also present
      an application to real data collected in a psychological experiment.

PMID- 27704241
TI  - Consistent individual differences in seed disperser quality in a seed-eating
      fish.
AB  - Animal-mediated seed dispersal (zoochory) is considered to be an important
      mechanism regulating biological processes at larger spatial scales. To date,
      intra-specific variation in seed disperser quality within seed-dispersing animals
      has not been studied. Here, I employed seed feeding trials to quantify individual
      differences in disperser quality within the common carp (Cyprinus carpio) using
      seeds of two aquatic plants: unbranched bur-reed (Sparganium emersum,
      Sparganiaceae) and arrowhead (Sagittaria sagittifolia, Alismataceae). I found
      substantial variation among carp individuals in their propensity to ingest seeds
      and their ability to digest them, resulting in up to 31-fold differences in the
      probability of seed dispersal. In addition, there were significant differences in
      the time that seeds are retained in their digestive systems, generating a twofold
      difference in the maximum distance over which they can potentially disperse
      seeds. I propose that seed-eating animal species consist of individuals that
      display continuous variation in disperser quality, with at one end of the
      continuum individuals that are likely to eat seeds, pass them unharmed through
      their digestive tract and transport them over large distances to new locations
      (i.e. high-quality seed dispersers) and at the other end individuals that rarely
      eat seeds, destroy most of the ones they ingest and transport the few surviving
      seeds over relatively short distances (low-quality seed dispersers). Although
      individual differences in seed dispersal quality could be the result of a variety
      of factors, these results underline the ecological and evolutionary potential of
      such variation for both plants and animals.

PMID- 27704242
TI  - Training residents in laparoscopic colorectal surgery: is supervised surgery
      safe?
AB  - BACKGROUND: Colorectal resections are increasingly performed laparoscopically,
      and training in laparoscopic resections in the Netherlands has shifted from a
      post-residency fellowship to training in residency. The question remains if this
      supervised surgery affects short-term patient outcome. METHODS: Between January
      2010 and July 2014, 523 consecutive patients, who underwent laparoscopic
      colorectal resection, were selected from a prospective single-center database.
      All data were obtained from the maintained database and retrospectively analyzed.
      We compared the short-term outcome of patients who underwent laparoscopic
      colorectal surgery by a supervised fifth- or sixth-year resident compared to
      patients who underwent laparoscopic colorectal surgery performed by a dedicated
      colorectal surgeon. Statistical analysis was performed using the Chi-square test
      for categorical variables and the t test for continuous variables. RESULTS:
      Almost 40 % of operations were performed by a resident with an even distribution
      in type of resection, except for the abdominal-perineal resection (residents vs.
      surgeon 3.57 vs. 8.26 %, p = 0.04) and the total number of patients who underwent
      preoperative chemoradiation (resident vs. surgeon 6.66 vs. 20.65 %, p = 0.04). No
      difference was found in operative time or per-operative blood loss. A higher
      conversion rate was found when surgery was performed by a supervised resident
      (residents vs. surgeon 17.34 vs. 9.17 %, p = 0.01), which could be attributed to
      case selection and one single year. No differences in major complications,
      oncological outcome and construction of a stoma were found. In the case of minor
      complications, a significantly increased percentage of bladder retention was
      found in the surgeon group (residents vs. surgeon 1 vs. 4.6 %, p = 0.03).
      CONCLUSIONS: In this study, we found that patient safety and short-term outcome
      are not adversely affected when laparoscopic colorectal surgery is performed by a
      supervised fifth- or sixth-year resident.

PMID- 27704243
TI  - Optimizing a living kidney donation program: transition to hand-assisted
      retroperitoneoscopic living donor nephrectomy and introduction of a passive
      polarizing three-dimensional display system.
AB  - BACKGROUND: Optimizing a living kidney donation program is important to guarantee
      a high grade of acceptance among potential donors. Hand-assisted
      retroperitoneoscopic donor nephrectomy (HARP) is an alternative to the open
      anterior approach (AA) technique. Problems associated to the learning curve could
      hinder a transition. 3D display technique seems to ease minimally invasive
      surgery. Aim of this study was to evaluate the learning curve during the
      transition from AA to HARP and the influence of the 3D display system on the
      established technique. METHODS: Observational study (n = 207) during transition
      to HARP and introduction of 3D display technique. RESULTS: Operation time (OT),
      warm ischemia time (WIT) and blood loss (BL) of HARP decreased during transition.
      Pairwise group comparison for OT showed a significant learning effect for the
      first 30 out of 50 HARPs without influence on graft function. Between AA and HARP
      no significant difference in OT (133 +/- 24 vs. 127 +/- 19 min, p = 0.25) but for
      WIT (23 +/- 28 vs. 126 +/- 40 s, p < 0.005) and BL (328 +/- 207 vs. 54 +/- 35 ml,
      p < 0.005) was seen. There was neither a significant difference in donors' nor
      recipients' eGFR. OT (98 +/- 16 vs. 106 +/- 19 min, p = 0.036) and WIT (97 +/- 37
      vs. 120 +/- 57 s, p = 0.023) were significantly shorter for the 3D technique
      compared to 2D. CONCLUSION: A transition to HARP is possible without additional
      risk for the donor or loss of quality for the recipient. The learning curve for
      HARP is steep and short. The introduction of 3D display technique after
      transition facilitates the surgical preparation and could further help to
      optimize HARP.

PMID- 27704244
TI  - Laparoscopic surgery in patients with colon cancer: a population-based analysis.
AB  - BACKGROUND: The long-term outcomes after laparoscopic surgery for colon cancer
      remain debatable, as randomized trials have reported similar outcomes for open
      and laparoscopic surgery but population-based data are scarce. Thus, it is
      unclear whether, outside of clinical trials, laparoscopic surgery that is
      performed as a standard clinical treatment has detrimental effects on patients'
      long-term survival. METHODS: This study examined a unified database of 30 German
      regional cancer registries for patients with colorectal cancer who were diagnosed
      between 2003 and 2011. Among 216,682 patients with colorectal carcinoma, we
      identified 37,068 patients with Union for International Cancer Control stage I
      III colon carcinoma (>12 cm from the anal verge), including 3825 patients (10.38
      %) who underwent laparoscopic surgery. Multivariate Cox regression analyses were
      also used to evaluate factors that influenced the likelihood of a patient
      undergoing laparoscopic surgery. Kaplan-Meier analysis with the log-rank test was
      used to analyse differences in short- and long-term survival outcomes after open
      or laparoscopic surgery. RESULTS: Younger age, lower T-stage, and left-sided
      surgery were independent predictors of the patient undergoing laparoscopic
      surgery (all, p < 0001). The 30-day mortality rate was significantly lower for
      patients who underwent laparoscopic surgery for left-sided tumours (odds ratio
      [OR] 0.49; 95 % confidence interval [CI] 0.33-0.77). Compared to open surgery,
      laparoscopic surgery was a significant and independent predictor of prolonged
      long-term survival for right- and left-sided surgeries (right-side, OR 0.67; 95 %
      CI 0.56-0.82; left-sided, OR 0.70; 95 % CI 0.62-0.78). CONCLUSION: Our results
      indicate that laparoscopic surgery provides favourable outcomes even when used
      outside controlled trials and should be considered as a standard treatment for
      patients with colon cancer.

PMID- 27704245
TI  - Pediatric neurofibromatosis type 2: clinical and molecular presentation,
      management of vestibular schwannomas, and hearing rehabilitation.
AB  - OBJECTIVE: This study aims to describe the clinical and molecular presentation of
      pediatric neurofibromatosis type 2 (NF2) and the subsequent management of
      vestibular schwannomas (VS) and hearing rehabilitation. METHODS: This is a single
      center retrospective study of neurofibromatosis type 2 diagnosed before the age
      of 18 years old from 1997. Natural history of vestibular schwannomas and surgical
      outcomes were evaluated using volumetric MRI, hearing, and facial nerve
      assessment. Patients included in chemotherapy protocols were excluded. RESULTS:
      From a database of 80 patients followed up for NF2 on a regular basis, 25
      patients were eligible (11 sporadic cases, 14 inherited in five families). The
      mean age at diagnosis was 11.6 years old. The average clinical follow-up was 6.5
      years. NF2 mutation was identified in 81 % of the probands. The average growth
      rate based on the maximum linear diameter (DGR) was 1.68 mm/year (n = 33, average
      follow-up 4.22 years) and 545 mm3/year in volumetric assessment (VGR) for VS
      larger than 1 cm (n = 21, average follow-up 3.4 years). In unoperated ears,
      hearing was stable in about 50 % of ears. The mean change in dB HL was 9.5
      dB/year for pure-tone average and 3.5 for speech-recognition threshold (n = 34,
      5.5 years 1-12). Eight children required removal through a translabyrinthine
      approach (mean follow-up was 4.5 years), six patients were operated on for
      hearing preservation (mean postoperative follow-up 4.3 years). Six patients were
      eligible for hearing rehabilitation with cochlear implantation (I), and five
      received placement of an auditory brainstem implant. CONCLUSION: Early diagnosis
      and treatment of small growing VS should be carefully discussed considering
      familial history and possible rehabilitation with a CI.

PMID- 27704246
TI  - Tadpole-shaped lateralized parietal atretic cephalocele associated with an
      ipsilateral lacrimal gland fistula and schizencephalic clefts.
AB  - BACKGROUND: Parietal atretic cephalocele (AC) and its associated intracranial
      venous anomalies, such as vertical embryonic positioning of the straight sinus
      (VEP of SS), have, in previous reports, been exclusively restricted to the
      midline. CLINICAL PRESENTATION: We report a patient with lateralized parietal AC
      on the right side. The AC was in the shape of a tadpole, with a large head and a
      long tail, extending to the proximity of the right external canthus, where a
      lacrimal gland fistula was observed. The superior sagittal sinus and VEP of SS
      were also displaced to the right side, although the sagittal suture was located
      at the midline. Schizencephalic clefts in the right posterior cortex were also
      observed. CONCLUSION: The parietal AC, which was initially located in the
      midline, could conceivably have been displaced to the right side by other
      developmental processes. However, the relationship between lateralized AC and
      associated multiple anomalies on the ipsilateral side is difficult to explain
      monogenetically. Our case study indicates that AC might have a broader spectrum
      of clinical symptoms than was once thought to be the case.

PMID- 27704247
TI  - Childhood acute basilar artery thrombosis successfully treated with mechanical
      thrombectomy using stent retrievers: case report and review of the literature.
AB  - INTRODUCTION: Acute basilar artery occlusion (ABAO) is an infrequent but
      potentially fatal cause of strokes in both adults and children, and it is usually
      due to vertebral artery dissection (VAD). VAD has been found to be usually a
      consequence of traumatic vertebral artery injury. ABAO usually presents with
      symptoms of acute ischemic stroke (AIS) of the posterior circulation or transient
      ischemic attack (TIA). It may lead to death or long-term disability if not
      promptly recanalized. Basilar artery recanalization in children can be achieved
      safely and with excellent clinical outcome using endovascular thrombectomy with
      the new generation self-expanding and retrievable stents. CLINICAL PRESENTATION:
      We report the case of a 23-month old baby that came to the emergency room of our
      hospital for progressive impairment of consciousness associated with widespread
      stiffness and plaintive cry, appeared after accidental fall from stroller. An
      emergency brain CT scan was obtained showing multiple infarction lesions in the
      brainstem and left cerebellum suggestive of acute stroke in posterior circulation
      territories. An MR scan with angiography and diffusion-weighted sequences
      confirmed the multiple infarction lesions and demonstrated poor representation of
      the flow signal at the V3 segment of the left vertebral artery and absent
      representation of the flow signal at the distal segment of the basilar artery
      suggestive of acute thrombotic occlusion. The patient was immediately referred to
      interventional neuroradiology unit, and digital subtraction angiography showed
      complete basilar artery occlusion and left vertebral artery dissection at
      extracranial V2-V3 segment. The patient underwent intra-arterial thrombectomy
      using stent retrievers and occlusion of the V2-V3 segment of the left vertebral
      artery. The patient survived and long-term outcome was excellent. CONCLUSIONS: To
      our knowledge, only nine cases of ABAO in children treated with intra-arterial
      thrombectomy have been previously reported in the literature. In only three
      cases, the Solitaire stent was applied. Our case is the first case of basilar
      artery occlusion treated with Solitaire stent, in a child under 24 months. The
      reports that are available so far indicate that basilar artery recanalization in
      children can be achieved safely and with excellent clinical outcome using
      endovascular thrombectomy with the new generation self-expanding and retrievable
      stents.

PMID- 27704248
TI  - Effect of postoperative major complications on prognosis after pancreatectomy for
      pancreatic cancer: a retrospective review.
AB  - PURPOSE: To investigate the impact of postoperative complications on survival
      after curative resection for pancreatic cancer. METHODS: We reviewed
      retrospectively the medical records of 122 patients who underwent curative R0
      resection for pancreatic cancer. Major complications included pancreatic fistula
      and hemorrhage of grade B or C according to the International Study Group of
      Pancreatic Fistula or Surgery criteria, and other complications of grade >=III
      according to the Clavien-Dindo classification. RESULTS: Thirty-eight patients (31
      %) suffered major postoperative complications and 40 patients (33 %) suffered
      minor complications only. Univariate survival analysis showed that patients with
      major complications had a significantly worse prognosis than those without major
      complications, with regard to recurrence-free survival (RFS) (P < 0.01) and
      overall survival (OS) (P < 0.01), whereas minor complications did not affect
      survival. Major complications significantly inhibited or delayed adjuvant
      chemotherapy. Multivariate survival analysis showed that the absence of
      postoperative major complications was an independent favorable factor for RFS
      (hazard ratio 0.48; 95 % confidence interval: 0.28-0.85) and OS (hazard ratio
      0.47; 95 % confidence interval 0.27-0.81). CONCLUSIONS: Postoperative major
      complications after pancreatectomy for pancreatic cancer affect the prognosis.

PMID- 27704249
TI  - LRP5/canonical Wnt signalling and healing of ischemic myocardium.
AB  - LRP5 (low-density lipoprotein receptor-related protein 5) activates canonical Wnt
      signalling. LRP5 plays multiple roles including regulation of lipoprotein and
      cholesterol homeostasis as well as innate immunity cell function. However, it is
      not known whether LRP5 has a role in the myocardium. The aim of this study was to
      investigate LRP5 and Wnt signalling in myocardial remodelling after acute
      myocardial infarction (MI). Wnt protein levels were determined in a
      hypercholesterolemic porcine model of MI, in Lrp5 -/- C57Bl6 mice, in cultured
      cardiomyocytes and in human explanted hearts with previous MI episodes. 21 days
      post-MI, there was upregulation of LRP5 in the ischemic myocardium of
      hypercholesterolemic pigs as well as an upregulated expression of proteins of the
      Wnt pathway. We demonstrate via overexpression and silencing experiments that
      LRP5 induces Wnt pathway activation in isolated cardiomyocytes. Hypoxia and lipid
      loading induced the expression of Wnt proteins, whereas this effect is blocked in
      LRP5-silenced cardiomyocytes. To characterize the function of the LRP5-Wnt axis
      upregulation in the heart, we induced MI in wild-type and Lrp5 -/- mice. Lrp5 -/-
      mice had significantly larger infarcts than Wt mice, indicating a protective role
      of LRP5 in injured myocardium. The LRP5 upregulation in post-MI hearts seen in
      pigs and mice was also evident in human hearts as dyslipidemic patients with
      previous episodes of ischemia have higher expression of LRP5 and Wnt-signalling
      genes than non-ischemic dilated hearts. We demonstrate an upregulation of LRP5
      and the Wnt signalling pathway that it is a prosurvival healing response of
      cardiomyocytes upon injury.

PMID- 27704250
TI  - Regulatory T Cells in SLE: Biology and Use in Treatment.
AB  - T regulatory cells (Tregs) represent a phenotypically and functionally
      heterogeneous group of lymphocytes that exert immunosuppressive activities on
      effector immune responses. Tregs play a key role in maintaining immune tolerance
      and homeostasis through diverse mechanisms which involve interactions with
      components of both the innate and adaptive immune systems. As in many autoimmune
      diseases, Tregs have been proposed to play a relevant role in the pathogenesis of
      systemic lupus erythematosus (SLE), an autoimmune disease characterized by a
      progressive breakdown of tolerance to self-antigens and the presence of
      concomitant hyperactive immune responses. Here, we review how Tregs dysfunction
      in SLE has been manipulated experimentally and preclinically in the attempt to
      restore, at last in part, the immune disturbances in the disease.

PMID- 27704251
TI  - Trauma-Informed HIV Prevention and Treatment.
AB  - The high prevalence of trauma and its negative impact on health and health
      promoting behaviors underscore the need for multi-level interventions to address
      trauma and its associated sequelae to improve physical and mental well-being in
      both HIV-infected and HIV-uninfected populations. Growing global awareness of the
      intersection of trauma and HIV has resulted in development and testing of
      interventions to address trauma in the context of HIV treatment and HIV
      prevention in the USA and globally. Despite increasing recognition of the
      widespread nature of trauma and the importance of trauma to HIV transmission
      around the globe, several gaps remain. Through a survey of the literature, we
      identified eight studies (published in the past 5 years) describing interventions
      to address the effects of trauma on HIV-related outcomes. In particular, this
      study focused on the levels of intervention, populations the interventions were
      designed to benefit, and types of trauma addressed in the interventions in the
      context of both HIV prevention and treatment. Remarkably absent from the HIV
      prevention, interventions reviewed were interventions designed to address
      violence experienced by men or transgender individuals, in the USA or globally.
      Given the pervasive nature of trauma experienced generally, but especially among
      individuals at heightened risk for HIV, future HIV prevention interventions
      universally should consider becoming trauma-informed. Widespread acknowledgement
      of the pervasive impact of gender-based violence on HIV outcomes among women has
      led to multiple calls for trauma-informed care (TIC) approaches to improve the
      effectiveness of HIV services for HIV-infected women. TIC approaches may be
      relevant for and should also be tested among men and all groups with high co
      occurring epidemics of HIV and trauma (e.g., men who have sex with men (MSM),
      transgendered populations, injection drug users, sex workers), regardless of type
      of trauma experience.

PMID- 27704254
TI  - An atypical case of a 2-year-old boy with acute kidney injury: a race against
      time. Questions.

PMID- 27704252
TI  - Extrarenal effects of FGF23.
AB  - Chronic kidney disease (CKD) is associated with an increased risk of
      cardiovascular mortality, infections, and impaired cognitive function. It is
      characterized by excessively increased levels of the phosphaturic hormone
      fibroblast growth factor 23 (FGF23) and a deficiency of its co-receptor Klotho.
      Despite the important physiological effect of FGF23 in maintaining phosphate
      homeostasis, there is increasing evidence that higher FGF23 levels are a risk
      factor for mortality and cardiovascular disease. FGF23 directly induces left
      ventricular hypertrophy via activation of the FGF receptor 4/calcineurin/nuclear
      factor of activated T cells signaling pathway. By contrast, the impact of FGF23
      on endothelial function and the development of atherosclerosis are poorly
      understood. The results of recent experimental studies indicate that FGF23
      directly impacts on hippocampal neurons and may thereby impair learning and
      memory function in CKD patients. Finally, it has been shown that FGF23 interferes
      with the immune system by directly acting on polymorphonuclear leukocytes and
      macrophages. In this review, we discuss recent data from clinical and
      experimental studies on the extrarenal effects of FGF23 with respect to the
      cardiovascular, central nervous, and immune systems.

PMID- 27704255
TI  - An atypical case of a 2-year-old boy with acute kidney injury: a race against
      time. Answers.

PMID- 27704253
TI  - Erratum to: Risk factors for progression in children and young adults with IgA
      nephropathy: an analysis of 261 cases from the VALIGA European cohort.

PMID- 27704256
TI  - Achieving remission of proteinuria in childhood CKD.
AB  - BACKGROUND: A multidrug treatment strategy that targets urinary proteins with an
      angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker
      (ARB) up-titrated to the respective maximum tolerated dose combined with
      intensified blood pressure (BP) control has been found to prevent renal function
      loss in adults with proteinuric nephropathies. Herein, we investigated the
      effects of this treatment protocol in the pediatric patient population. METHODS:
      From May 2002 to September 2014 we included in this observational, longitudinal,
      cohort study 20 consecutive children with chronic nephropathies and 24-h
      proteinuria of >200 mg who had received ramipril and losartan up-titrated to the
      respective maximum approved and tolerated doses [mean ( standard deviation)
      dose:2.48 (1.37) mg/m2 and 0.61 (0.46) mg/kg daily, respectively]. The primary
      efficacy endpoint was a >50 % reduction in 24-h proteinuria to <200 mg
      (remission). Secondary outcomes included changes in proteinuria, serum albumin,
      BP, and glomerular filtration rate (GFR). RESULTS: Mean (+/- standard deviation)
      patient age at inclusion was 13.8 +/- 2.8 years, and the median [interquartile
      range (IQR)] serum creatinine level and proteinuria were 0.7 (0.6-1.0) mg/dl and
      690 (379-1270) mg/24 h or 435 (252-711) mg/m2/24 h, respectively. Proteinuria
      significantly decreased by month 6 of follow-up, and serum albumin levels
      increased over a median follow-up period of 78 (IQR 39-105) months. In the nine
      children who achieved remission, proteinuria reduction persisted throughout the
      whole follow-up without rebounds. The GFR improved in those children who achieved
      remission and worsened in those who did not. The mean GFR slopes differed
      significantly between these two groups (p < 0.05), being positive in those
      children with remission and negative in those without remission (+0.023 +/- 0.15
      vs.-0.014 +/- 0.23 ml/min/1.73 m2/month, respectively), whereas BP control was
      similar between the two groups. Hyperkalemia was observed in two children.
      CONCLUSIONS: Combination therapy with maximum approved doses of ACE inhibitors
      and ARBs is a safe strategy which may achieve proteinuria remission with kidney
      function stabilization or even improvement in a substantial proportion of
      children with proteinuric nephropathies.

PMID- 27704258
TI  - Radial Ultrasound-Assisted Transbronchial Biopsy: A New Diagnostic Approach for
      Non-Resolving Pulmonary Infiltrates in Neutropenic Hemato-Oncological Patients.
AB  - The role of radial-endobronchial ultrasound (R-EBUS) assisted transbronchial
      biopsy (TBB) for the diagnosis of peripheral pulmonary lesions is well
      established. However, no study has addressed its safety and value in hemato
      oncological patients presenting with non-resolving infiltrates during persistent
      febrile neutropenia. To assess safety and feasibility of R-EBUS assisted TBB in
      severe thrombocytopenic and neutropenic patients. Over a period of 18 months,
      eight patients were assessed with R-EBUS assisted TBB after adequate platelet
      transfusion. This technique allowed precise localisation and sampling of the
      pulmonary lesions in seven of eight patients. In the seven patients, R-EBUS
      assisted TBB enabled treatment optimization. Invasive fungal infection was
      diagnosed in four patients, idiopathic acute fibrinous and organising pneumonia
      in three patients, and a granulomatous inflammation of undetermined origin in one
      patient. Importantly, no complications, such as bleeding, were observed. R-EBUS
      assisted TBB is a promising and safe procedure for the evaluation of nonresolving
      pulmonary infiltrates in febrile neutropenic hemato-oncological patients.

PMID- 27704257
TI  - Diagnosis and Treatment of Childhood Migraine.
AB  - OPINION STATEMENT: While the diagnosis of migraine in children is generally
      straightforward, treatment can seem complex with a number of medication choices,
      many of which are used "off label." Patients with intermittent migraines can
      often be managed with ibuprofen or naproxen taken as needed. Unfortunately, by
      the time that children present to our practice, they have often tried these
      medications without improvement. Triptans are frequently prescribed to these
      patients with good success. It is important to make the patient aware of the
      possible associated serotonergic reactions. If the patient is having more than
      one headache per week or the headaches are prolonged, prophylactic treatment is
      indicated. In our practice, the overwhelming majority of these patients will be
      treated with amitriptyline or topiramate. We generally allow side effect
      tolerability to guide our choice of medication. Cyproheptadine is often used in
      younger patients as it comes in a liquid form. There is evidence supporting the
      use of propranolol, though the potential worsening of underlying asthma symptoms
      may limit its use, and sodium valproate, which must be used with caution in
      female patients of childbearing age due to significant teratogenicity risks.
      Other prophylactic treatments with less robust evidence include the antiepileptic
      drugs gabapentin, zonisamide, and levetiracetam; calcium channel blockers such as
      verapamil and amlodipine; and the angiotensin receptor blocking agent candasartin
      (not available in the USA). Almost all patients in our practice are advised to
      take magnesium supplementation. Magnesium is a supplement with relatively few
      adverse effects and good evidence for improvement of migraine symptoms. We
      evaluate lifestyle issues and comorbidities in all our patients. Ignoring these
      will make successful treatment near impossible. Good sleep, adequate hydration,
      appropriate diet, and exercise are vitally important. Finally, most of our
      patients benefit from a psychology evaluation with cognitive behavioral therapy.
      Stress management and biofeedback are tremendously helpful in improving quality
      of life in migraineurs.

PMID- 27704259
TI  - The Emulsified PFC Oxycyte(r) Improved Oxygen Content and Lung Injury Score in a
      Swine Model of Oleic Acid Lung Injury (OALI).
AB  - PURPOSE: Perfluorocarbons (PFCs) can transport 50 times more oxygen than human
      plasma. Their properties may be advantageous in preservation of tissue viability
      in oxygen-deprived states, such as in acute lung injury. We hypothesized that an
      intravenous dose of the PFC emulsion Oxycyte(r) would improve tissue oxygenation
      and thereby mitigate the effects of acute lung injury. METHODS: Intravenous oleic
      acid (OA) was used to induce lung injury in anesthetized and instrumented
      Yorkshire swine assigned to three experimental groups: (1) PFC post-OA received
      Oxycyte(r) (5 ml/kg) 45 min after oleic acid-induced lung injury (OALI); (2) PFC
      pre-OA received Oxycyte(r) 45 min before OALI; and (3) Controls which received
      equivalent dose of normal saline. Animals were observed for 3 h after OALI began,
      and then euthanized. RESULTS: The median survival times for PFC post-OA, PFC pre
      OA, and control were 240, 87.5, and 240 min, respectively (p = 0.001). Mean
      arterial pressure and mean pulmonary arterial pressure were both higher in the
      PFC post-OA (p < 0.001 for both parameters). Oxygen content was significantly
      different between PFC post-OA and the control (p = 0.001). Histopathological
      grading of lung injury indicated that edema and congestion was significantly less
      severe in the PFC post-OA compared to control (p = 0.001). CONCLUSION: The
      intravenous PFC Oxycyte(r) improves blood oxygen content and lung histology when
      used as a treatment after OALI, while Oxycyte(r) used prior to OALI was
      associated with increased mortality. Further exploration in other injury models
      is indicated.

PMID- 27704260
TI  - Axillary web syndrome is not a risk factor for lymphoedema after 10 years of
      follow-up.
AB  - OBJECTIVE: The objective of this study was to evaluate the association between
      axillary web syndrome and the development of lymphoedema after 10 years of follow
      up. METHODOLOGY: A prospective observational study in a hospital cohort of women
      diagnosed with breast cancer and treated at a referral centre for cancer.
      Patients were followed according to the routine of the hospital's physical
      therapy service. In addition, a review of medical records was conducted for the
      period between 5 and 10 years of follow-up. Data on patient characteristics,
      treatment, tumour and postoperative complications were collected. RESULTS: In
      all, 964 patients were included, mostly <65 years old (75 %) and classified as
      being overweight (68 %). Disease was diagnosed as being up to stage IIA in 54.9 %
      of the cases; 65.1% underwent mastectomy and 83.8% had total axillary dissection.
      As adjuvant treatment, 61 % underwent chemotherapy, 63.5 % radiotherapy and 68 %
      hormone therapy. Among surgical complications, 62.6 % of patients had seroma,
      40.7 % had necrosis, 35.9 % axillary web syndrome and 31.4 % lymphoedema. There
      was no association between axillary web syndrome and the development of
      lymphoedema (OR = 0.87, 95 % CI 0.65 to 1.15, p = 0.329). CONCLUSION: The
      occurrence of axillary web syndrome was not a risk factor for lymphoedema after
      10 years of follow-up.

PMID- 27704261
TI  - Do-not-resuscitate consent signed by patients indicates a more favorable quality
      of end-of-life care for patients with advanced cancer.
AB  - PURPOSE: Do-not-resuscitate (DNR) consent is crucial in end-of-life (EOL) care
      for patients with advanced cancer. However, DNR consents signed by patients (DNR
      P) and surrogates (DNR-S) reflect differently on patient autonomy and awareness.
      METHODS: This retrospective study enrolled advanced cancer patients treated at
      National Taiwan University Hospital, Hsin-Chu Branch between 2012 and 2014.
      Patients who signed DNR consent at other hospitals were excluded; the remaining
      patients were subsequently classified into DNR-S and DNR-P groups. RESULTS: We
      enrolled 1495 patients. The most prevalent primary cancers were hepato-biliary
      pancreatic (26.9 %), lung (16.3 %), and colorectal (14.0 %) cancers. We
      classified 965 (64.5 %) and 530 (35.5 %) patients into the DNR-S and DNR-P
      groups, respectively. Significant differences were observed between both groups
      regarding gender (p = 0.002), age (p < 0.001), and the Eastern Cooperative
      Oncology Group performance (p < 0.001) and educational (p < 0.001) status levels.
      The median survival times after DNR consent signature were 5.0 days (95 %
      confidence interval [CI] 4.4-5.6 days) and 14.0 days (95 % CI 12.1-15.9 days) in
      the DNR-S and DNR-P groups, respectively (p < 0.001). The median good death
      evaluation (GDE) scores were 5.4 (95 % CI 4.9-6.0) and 13.7 (95 % CI 12.7-14.6)
      in the DNR-S and DNR-P groups, respectively (p < 0.001). Univariate and
      multivariate analyses revealed that DNR-S was an independent factor for
      significantly low GDE scores (i.e., poor EOL care quality). CONCLUSION: The DNR
      concept is emerging; however, the DNR-P percentage remains low (35.6 %) in
      patients with advanced cancer. DNR-P significantly improves the EOL care quality.

PMID- 27704262
TI  - Risk factors for same-admission mortality after pathologic fracture secondary to
      metastatic cancer.
AB  - PURPOSE: The skeleton is the third most common site of cancer metastases.
      Approximately 10 % of patients with bone metastases will develop a pathologic
      fracture, with significant associated morbidity and mortality. The purpose of
      this study was to identify risk factors for same-admission mortality after
      pathologic fractures secondary to metastatic cancer. METHODS: The Nationwide
      Inpatient Sample database was queried from 2002 to 2013 for hospitalized patients
      with diagnoses of pathologic fracture and a primary cancer at high risk for
      skeletal metastasis. Univariate and multivariate analyses were performed to
      determine risk factors associated with same-admission mortality after fracture.
      RESULTS: A total of 371,163 patients were identified. The spine was the most
      common site of pathologic fracture (68.0 %) followed by lower extremity (25.0 %)
      and upper extremity (8.7 %). The following factors were independently associated
      with increased mortality (p < 0.001): cancer of lung or unspecified location;
      fracture of upper or lower extremity; male gender; age >=65; non-Medicare
      insurance; coexisting congestive heart failure, chronic pulmonary disease, renal
      failure, or liver disease; and postoperative surgical site infection, acute
      myocardial infarction, pulmonary embolism, or pneumonia. Closed reductions were
      associated (p < 0.001) with increased mortality while open or percutaneous
      surgical treatments were protective (p < 0.001) against mortality. CONCLUSIONS:
      Pathologic fractures are a devastating consequence of metastatic bone disease,
      contributing significantly to morbidity and mortality. Numerous demographic and
      medical factors are associated with increased same-admission mortality. This data
      is useful for counseling patients with skeletal metastatic disease and should be
      taken into consideration when conducting routine skeletal surveillance in
      patients with metastatic cancer.

PMID- 27704263
TI  - Mathematical Model of the Dynamics of Fish, Waterbirds and Tourists in the Djoudj
      National Park, Senegal.
AB  - In the present paper, we propose and analyze a harvested predator-prey model that
      incorporates the dynamics of tourists in the Djoudj National Park of Birds,
      Senegal. The model describes the impact of migration of waterbirds and seasonal
      fishing on the global coexistence of species in the site of the Djoudj. By the
      Mahwin continuation theorem of coincidence degree theory, we investigate the
      existence of a positive periodic solution. The global asymptotic stability is
      discussed by constructing a suitable Lyapunov functional. Some computational
      results are also addressed.

PMID- 27704264
TI  - Analysis of molecular alterations in laterally spreading tumors of the
      colorectum.
AB  - BACKGROUND: Colorectal laterally spreading tumors (LSTs) are classified into LST
      Gs and LST-NGs, according to macroscopic findings. In the present study, we
      determined the genetic and epigenetic alterations within colorectal LSTs and
      protruding adenomas. METHODS: A crypt isolation method was used to isolate DNA
      from tumors and normal glands of 73 macroscopically verified colorectal LSTs
      (histologically defined adenomas; 38 LST-Gs and 35 LST-NGs) and 36 protruding
      adenomas. The DNA was processed using polymerase chain reaction (PCR)
      microsatellite assays, single-strand conformation polymorphism (SSCP) assays, and
      pyrosequencing to detect chromosomal allelic imbalance (AI), mutations in APC,
      KRAS, and TP53, and the methylation of MLH1, MGMT, CDKN2A, HPP1, RASSF2A, SFRP1,
      DKK1, ZFP64, and SALL4 genes. In addition, methylation status was examined using
      the following set of markers: MIN1, MINT2, MINT31, MLH1, and CDKN2A (with
      classification of negative/low and high). Microsatellite instability (MSI) was
      also examined. RESULTS: 5q AI and methylation of the SFRP1 and SALL4 genes were
      common molecular events in both LST-Gs and LST-NGs. Neither MSI nor mutations in
      BRAF ware observed in the LSTs. TP53 mutations were rarely found in LSTs. The
      frequencies of KRAS and APC mutations and the methylation levels of ZFP64,
      RASSF2A, and HPP1 genes were significantly higher in LST-Gs than in LST-NGs.
      Protruding adenomas showed alterations common to LST-Gs. Negative/low methylation
      status was common among the three types of tumors. CONCLUSION: Combined genetic
      and epigenetic data suggested that the molecular mechanisms of tumorigenesis were
      different between LST-Gs and LST-NGs.

PMID- 27704265
TI  - Biliary carcinogenesis in pancreaticobiliary maljunction.
AB  - Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the
      pancreatic and bile ducts join anatomically outside the duodenal wall. Because of
      the excessive length of the common channel in PBM, sphincter action does not
      directly affect the pancreaticobiliary junction, which allows pancreatic juice to
      reflux into the biliary tract. According to the results of a nationwide survey,
      bile duct and gallbladder cancers were found in 6.9 and 13.4 % of adult patients
      with congenital biliary dilatation, respectively, and in 3.1 and 37.4 % of those
      with PBM without biliary dilatation, respectively. Biliary tract cancers develop
      about 15-20 years earlier in patients with PBM than in individuals without PBM;
      they sometimes develop as double cancers. Carcinogenesis is strongly associated
      with stasis of bile intermingled with refluxed pancreatic juice. Epithelial cells
      in the biliary tract of PBM patients are under constant attack from activated
      pancreatic enzymes, increased secondary bile acids, or other mutagens. This can
      result in hyperplastic change with increased cell proliferation activity, and in
      turn, oncogene and/or tumor suppressor gene mutations in the epithelia, leading
      to the biliary tract carcinogenesis. The carcinogenesis of biliary tract cancer
      accompanying PBM is considered to involve a hyperplasia-dysplasia-carcinoma
      sequence induced by chronic inflammation caused by the reflux of pancreatic juice
      into the biliary tract, which differs from the adenoma-carcinoma sequence or the
      de novo carcinogenesis associated with biliary tract cancers in the population
      without PBM. Patients with a relatively long common channel have a similar,
      albeit slightly lower, risk for gallbladder cancer compared with PBM patients.

PMID- 27704266
TI  - Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma.
AB  - BACKGROUND: Lenvatinib is an oral inhibitor of vascular endothelial growth factor
      receptor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth
      factor receptor alpha, RET, and KIT. This phase 2, single-arm, open-label
      multicenter study evaluated lenvatinib in advanced hepatocellular carcinoma
      (HCC). METHODS: Patients with histologically/clinically confirmed advanced HCC
      who did not qualify for surgical resection or local therapies received lenvatinib
      at a dosage of 12 mg once daily (QD) in 28-day cycles. The primary efficacy
      endpoint was time to progression (TTP) per modified Response Evaluation Criteria
      in Solid Tumors v1.1; secondary efficacy endpoints included objective response
      rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS:
      Between July 2010 and June 2011, 46 patients received lenvatinib at sites across
      Japan and Korea. The median TTP, as determined by independent radiological
      review, was 7.4 months [95 % confidence interval (CI): 5.5-9.4]. Seventeen
      patients (37 %) had partial response and 19 patients (41 %) had stable disease
      (ORR: 37 %; DCR: 78 %). Median OS was 18.7 months (95 % CI: 12.7-25.1). The most
      common any-grade adverse events (AEs) were hypertension (76 %), palmar-plantar
      erythrodysesthesia syndrome (65 %), decreased appetite (61 %), and proteinuria
      (61 %). Dose reductions and discontinuations due to AEs occurred in 34 (74 %) and
      10 patients (22 %), respectively. Median body weight was lower in patients with
      an early (<30 days) dose withdrawal or reduction than in those without.
      CONCLUSIONS: Lenvatinib 12-mg QD showed clinical activity and acceptable toxicity
      profiles in patients with advanced HCC, but early dose modification was necessary
      in patients with lower body weight. Further development of lenvatinib in HCC
      should consider dose modification by body weight. TRIAL REGISTRATION ID:
      www.ClinicalTrials.gov NCT00946153.

PMID- 27704267
TI  - MicroRNA-34c-3p promotes cell proliferation and invasion in hepatocellular
      carcinoma by regulation of NCKAP1 expression.
AB  - PURPOSE: Our previous miRNA profiling study indicated that microRNA-34c-3p (miR
      34c-3p) was overexpressed and associated with survival in HCC. This study is
      aimed to confirm its clinical significance and explore the function and
      underlying mechanism of miR-34c-3p in HCC. METHODS: We first evaluated miR-34c-3p
      expression and its relationship with prognosis in HCC patients. We then
      established stable HCC cell lines with miR-34c-3p overexpression and knockdown by
      the lentiviral packaging systems and performed the functional assays in vitro and
      in vivo, respectively. We next identified the target of miR-34c-3p by using
      microRNA target databases and dual-luciferase assay. Finally, the correlation
      between the expression of miR-34c-3p and the target gene was analyzed by
      immunohistochemistry and qRT-PCR in HCC tissues and hepatoma xenografts. RESULTS:
      Overexpressed miR-34c-3p was confirmed in HCC tissues and significantly
      associated with poor survival of HCC patients. miR-34c-3p expression was also
      recognized as an independent risk factor for DFS and OS in multivariate analysis.
      Ectopic expression of miR-34c-3p significantly promotes the proliferation, colony
      formation, invasion and cell cycle regression of HCC cell lines. Knockdown of miR
      34c-3p remarkably blocked hepatoma growth in the xenograft model. miRNA target
      databases and luciferase reporter assay showed that NCKAP1 was a direct target of
      miR-34c-3p in HCC cells and the high expression of NCKAP1 in HCC tissues is
      significantly correlated with low expression of miR-34c-3p and associated with a
      favorable prognosis of HCC patients. CONCLUSION: The current study demonstrates
      that miR-34c-3p functions as a tumor promoter by targeting NCKAP1 that is
      associated with prognosis in HCC. miR-34c-3p and NCKAP1 may be new potential
      molecular targets for HCC therapy.

PMID- 27704269
TI  - Linked CD4 T Cell Help: Broadening Immune Attack Against Cancer by Vaccination.
AB  - In the last decade, immunotherapy with monoclonal antibodies targeting
      immunological check points has become a breakthrough therapeutic modality for
      solid cancers. However, only up to 50 % of patients benefit from this powerful
      approach. For others vaccination might provide a plausible addition or
      alternative. For induction of effective anticancer immunity CD4+ T cell help is
      required, which is often difficult to induce to self cancer targets because of
      tolerogenic mechanisms. Our approach for cancer vaccines has been to incorporate
      into the vaccine design sequences able to activate foreign T cell help, through
      genetically linking cancer targets to microbial sequences (King et al. in Nat Med
      4(11):1281-1286, 1998; Savelyeva et al. in Nat Biotechnol 19(8):760-764, 2001).
      This harnesses the non-tolerized CD4 T cell repertoire available in patients to
      help induction of effective immunity against fused cancer antigens. Multiple
      immune effector mechanisms including antibody, CD8+ T cells as well as CD4
      effector T cells can be activated using this strategy. Delivery via DNA vaccines
      has already indicated clinical efficacy. The same principle of linked T cell help
      has now been transferred to other novel vaccine modalities to further potentiate
      immunity against cancer targets.

PMID- 27704268
TI  - Chemotherapy response and survival of inflammatory breast cancer by hormone
      receptor- and HER2-defined molecular subtypes approximation: an analysis from the
      National Cancer Database.
AB  - PURPOSE: To study the impact of hormone receptor (HR)- and human epidermal growth
      factor receptor 2 (HER2)-defined subtypes on survival of inflammatory breast
      cancer (IBC), and to determine whether sensitivity to neoadjuvant chemotherapy
      (NAC) varies with subtypes in a large IBC population. METHODS: We analyzed 593
      IBCs with known HR/HER2 statuses between 2010 and 2011 from National Cancer
      Database. We compared pathologic complete response (pCR) rates among four
      molecular subtypes by Chi-square test. Overall survival (OS) was compared among
      four subtypes and patients with or without pCR using log-rank test. Multivariate
      Cox model was performed to identify the impact of molecular subtype and other
      prognostic factors on OS. RESULTS: Of the 593 patients included, 231 (39.0 %)
      patients had HR+/HER2- tumors, 98 (16.5 %) had HR+/HER2+ disease, 112 (18.9 %)
      were HR-/HER2 + patients, and 152 (25.6 %) had triple-negative subtype. The pCR
      rates differed significantly by subtype (P < 0.001): HR-/HER2+ showed the
      highest, and HR+/HER2- exhibited the lowest. Multivariate analysis showed that
      triple-negative and HR+/HER2- IBCs had significantly worse survival compared with
      HR+/HER2+ or HR-/HER2+ subtype (P < 0.01 for all comparisons). Additional factors
      associated with worse OS included more comorbidities, lack or incomplete surgical
      resection, absence of radiotherapy, lack of hormone therapy, and more advanced
      stage. CONCLUSIONS: IBC is an aggressive heterogeneous disease with distinct
      molecular subtypes associated with differential outcomes and sensitivities to
      NAC. Unlike in noninflammatory breast cancer, in IBC HR + disease was not
      associated with favorable prognosis. Triple-negative and HR+/HER2- subtypes are
      independent predictors for suboptimal OS in IBC.

PMID- 27704270
TI  - New Structural Templates for Clinically Validated and Novel Targets in
      Antimicrobial Drug Research and Development.
AB  - The development of bacterial resistance against current antibiotic drugs
      necessitates a continuous renewal of the arsenal of efficacious drugs. This
      imperative has not been met by the output of antibiotic research and development
      of the past decades for various reasons, including the declining efforts of large
      pharma companies in this area. Moreover, the majority of novel antibiotics are
      chemical derivatives of existing structures that represent mostly step
      innovations, implying that the available chemical space may be exhausted. This
      review negates this impression by showcasing recent achievements in lead finding
      and optimization of antibiotics that have novel or unexplored chemical
      structures. Not surprisingly, many of the novel structural templates like
      teixobactins, lysocin, griselimycin, or the albicidin/cystobactamid pair were
      discovered from natural sources. Additional compounds were obtained from the
      screening of synthetic libraries and chemical synthesis, including the gyrase
      inhibiting NTBI's and spiropyrimidinetrione, the tarocin and targocil inhibitors
      of wall teichoic acid synthesis, or the boronates and diazabicyclo[3.2.1]octane
      as novel beta-lactamase inhibitors. A motif that is common to most clinically
      validated antibiotics is that they address hotspots in complex biosynthetic
      machineries, whose functioning is essential for the bacterial cell. Therefore, an
      introduction to the biological targets-cell wall synthesis, topoisomerases, the
      DNA sliding clamp, and membrane-bound electron transport-is given for each of the
      leads presented here.

PMID- 27704271
TI  - Synthesis of Antibiotics.
AB  - The synthesis of beta-lactams, tetracyclines, and erythromycins as three of the
      major families of antibiotics will be described herein. We will describe why
      these antibiotics were the ultimate synthetic targets in the past and how modern
      synthetic organic chemistry has evolved to address these challenges with new,
      improved strategies and methods. An additional aspect we would like to highlight
      here is the fact that these first syntheses had to be particularly creative as
      most of the modern synthetic methods were not available at that time, or were
      developed in the course of these syntheses.

PMID- 27704273
TI  - Joint Meeting of the German Association of Endocrine Surgeons (CAEK) and the
      British Association of Endocrine and Thyroid Surgeons (BAETS).

PMID- 27704272
TI  - Actinobacteria and Myxobacteria-Two of the Most Important Bacterial Resources for
      Novel Antibiotics.
AB  - Bacteria have been by far the most promising resource for antibiotics in the past
      decades and will in all undoubtedly remain an important resource of innovative
      bioactive natural products in the future. Actinobacteria have been screened for
      many years, whereas the Myxobacteria have been underestimated in the past. Even
      though Actinobacteria belong to the Gram-positive and Myxobacteria to the Gram
      negative bacteria both groups have a number of similar characters, as they both
      have huge genomes with in some cases more than 10kB and a high GC content and
      they both can differentiate and have often cell cycles including the formation of
      spores. Actinobacteria have been used for the antibiotic research for many years,
      hence it is often discussed whether this resource has now been exhaustively
      exploited but most of the screening programs from pharmaceutical companies were
      basing on the cultivation mainly of members of the genus Streptomyces or
      Streptomyces like strains (e.g., some Saccharopolyspora, Amycolatopsis or
      Actinomadura species) by use of standard methods so that many of the so called
      "neglected" Actinobacteria were overlooked the whole time. The present review
      gives an overview on the state of the art regarding new bioactive compounds with
      a focus on the marine habitats. Furthermore, the evaluation of Myxobacteria in
      our ongoing search for novel anti-infectives is highlighted.

PMID- 27704274
TI  - Risk-adjusted treatment selection and outcome of patients with acute
      cholecystitis.
AB  - PURPOSE: Age and comorbidities increase the surgical risk for patients with acute
      cholecystitis and impact on the initial treatment selection. The aim of this
      article is the implementation of objective risk criteria that may be used to
      select the most appropriate treatment. METHODS: We carried out a prospective
      cohort study of all patients who were admitted to the hospital with a diagnosis
      of acute cholecystitis during 2014. They were initially allocated to three
      different treatment groups according to cholecystitis grade, number of days from
      clinical onset, and surgical risk scores as follows: immediate surgery by sepsis
      (EmergS), early surgery (EarlyS), or medical treatment group (MedT). Differences
      in the outcomes between the treatment groups were evaluated using bivariate and
      logistic regression analyses. RESULTS: A total of 149 patients were admitted; 44
      % were >80 years old and 40 % were American Society of Anesthesiologists (ASA) >
      II. The mortality rate of the series was 0 % in EarlyS, 17 % in MedT, and 19 % in
      EmergS. The mortality rate was significantly associated with a higher degree of
      cholecystitis, age, and worse score values in risk scales and Charlson index.
      Logistic regression identified that the only independent predictors of death at
      the time of admission were the degree of cholecystitis (OR 2.87, p = 0.018) and
      the Portsmouth Physiological and Operative Severity Score for the enumeration of
      Mortality and Morbidity (P-POSSUM) score (OR 1.14, p = 0.001). CONCLUSION: The
      evaluation for the initial treatment in acute cholecystitis should include a
      systematic determination of the degree of cholecystitis and a surgical risk
      assessment. Tokyo guideline recommendations should be reviewed.

PMID- 27704275
TI  - Dynamic quantitative proteomics characterization of TNF-alpha-induced
      necroptosis.
AB  - Emerging evidence suggested that necroptosis has essential functions in many
      human inflammatory diseases, but the molecular mechanisms of necroptosis remain
      unclear. Here, we employed SILAC quantitatively dynamic proteomics to compare the
      protein changes during TNF-alpha-induced necroptosis at different time points in
      murine fibrosarcoma L929 cells with caspase-8 deficiency, and then performed the
      systematical analysis on the signaling networks involved in the progress using
      bioinformatics methods. Our results showed that a total of 329, 421 and 378
      differentially expressed proteins were detected at three stages of necroptosis,
      respectively. Gene ontology and ingenuity pathway analysis (IPA) revealed that
      the proteins regulated at early stages of necroptosis (2, 6 h) were mainly
      involved in mitochondria dysfunction, oxidative phosphorylation and Nrf-2
      signaling, while the expression levels of the proteins related to ubiquitin, Nrf
      2, and NF-kappaB pathways were found to have changes at last stages of
      necroptosis (6, 18 h). Taken together, we demonstrated for the first time that
      dysfunction of mitochondria and ubiquitin-proteasome signaling contributed to the
      initiation and execution of necroptosis. These findings may provide clues for the
      identification of important regulators in necroptosis and the development of
      novel therapeutic strategies for the related diseases.

PMID- 27704276
TI  - Identification of cytotoxic mediators and their putative role in the signaling
      pathways during docosahexaenoic acid (DHA)-induced apoptosis of cancer cells.
AB  - Docosahexaenoic acid (DHA), an important w-3 fatty acid exhibits differential
      behavior in cancer cells of neural origin when compared to that in normal healthy
      astrocytes. Treatment of C6 glioma and SH-SY5Y cell lines and primary astrocytes,
      representing the neoplastic cells and normal healthy cells respectively, with 100
      uM DHA for 24 h showed significant loss of cell viability in the both the cancer
      cells as determined by MTT assay, whereas the primary astrocytes cultures were
      unaffected. Such loss of cell viability was due to apoptosis as confirmed by
      TUNEL staining and caspase-3 activation in cancer cells. Proteomic approach,
      employing 2-dimensional gel electrophoresis (2DE), difference gel electrophoresis
      (DIGE), and MALDI-TOF-TOF analysis identified six proteins which unlike in the
      astrocytes, were differently altered in the cancer cells upon exposure to DHA,
      suggesting their putative contribution in causing apoptosis in these cells. Of
      these, annexin A2, calumenin, pyruvate kinase M2 isoform, 14-3-3zeta were
      downregulated while aldo keto reductase-1B8 (AKR1B8) and glutathione-S
      transferase P1 subunit (GSTP1) showed upregulation by DHA in the cancer cells.
      siRNA-mediated knockdown of AKR1B8 and GSTP1 inhibit DHA-induced apoptosis
      confirming their role in apoptotic process. Furthermore, western blot analysis
      identified upregulation of PPARalpha and the MAP kinases, JNK and p38 as well as
      increased ROS production selectively in the cell lines. Results suggest that DHA
      selectively induces apoptosis in the neural cell lines by regulating the
      expression of the above proteins to activate multiple apoptotic pathways which in
      association with excess ROS and activated MAPKs promote cell death.

PMID- 27704277
TI  - Branch regeneration induced by sever damage in the brown alga Dictyota dichotoma
      (dictyotales, phaeophyceae).
AB  - Tissue wounds are mainly caused by herbivory, which is a serious threat for macro
      algae, and brown algae are known to regenerate branches or buds in response to
      wounding. In the present paper, we describe a branch regeneration system, induced
      by sever damage, in the brown alga Dictyota dichotoma. Segmentations of juvenile
      thalli induced branch regenerations unless explants possessed apical cells.
      Apical excisions in distinct positions elucidated that disruption of an apical
      cell or disconnection of tissue with an apical cell triggered the branch
      regeneration. Furthermore, spatial positions of regenerated branches seemed to be
      regulated by the apical region, which was assumed to generate inhibitory effects
      for lateral branch regeneration. Mechanical incision, which disrupted tissue
      continuity with the apical region, induced branch regeneration preferentially
      below the incision. Although we were unable to identify the candidate inhibitory
      substance, our results suggested that the apical region may have an inhibitory
      effect on lateral branch regeneration. Additionally, observations of branch
      regeneration showed that all epidermal cells in D. dichotoma possess the ability
      to differentiate into apical cells, directly. This may be the first report of
      algal transdifferentiation during the wound-stress response.

PMID- 27704278
TI  - Comparison of headspace-oxylipin-volatilomes of some Eastern Himalayan mosses
      extracted by sample enrichment probe and analysed by gas chromatography-mass
      spectrometry.
AB  - Mosses have an inherent adaptability against different biotic and abiotic
      stresses. Oxylipins, the volatile metabolites derived from polyunsaturated fatty
      acids (PUFAs), play a key role in the chemical defence strategy of mosses. In the
      present study, a comparative survey of these compounds, including an
      investigation into their precursor fatty acids (FAs), was carried out for the
      first time on the mosses Brachymenium capitulatum (Mitt.) Paris, Hydrogonium
      consanguineum (Thwaites & Mitt.) Hilp., Barbula hastata Mitt., and Octoblepharum
      albidum Hedw. collected from the Eastern Himalayan Biodiversity hotspot. Their
      headspace volatiles were sampled using a high-efficiency sample enrichment probe
      (SEP) and were characterized by gas chromatography-mass spectrometric analysis.
      FAs from neutral lipid (NL) and phospholipid (PL) fractions were also evaluated.
      Analysis of the oxylipin volatilome revealed the generation of diverse
      metabolites from C5 to C18, dominated by alkanes, alkenes, saturated and
      unsaturated alcohols, aldehydes, ketones and cyclic compounds, with pronounced
      structural variations. The C6 and C8 compounds dominated the total volatilome of
      all the samples. Analyses of FAs from membrane PL and storage NL highlighted the
      involvement of C18 and C20 PUFAs in oxylipin generation. The volatilome of each
      moss is characterized by a 'signature oxylipin mixture'. Quantitative differences
      in the C6 and C8 metabolites indicate their phylogenetic significance.

PMID- 27704279
TI  - Improvement of the insertion axis for cochlear implantation with a robot-based
      system.
AB  - It has previously reported that alignment of the insertion axis along the basal
      turn of the cochlea was depending on surgeon' experience. In this experimental
      study, we assessed technological assistances, such as navigation or a robot-based
      system, to improve the insertion axis during cochlear implantation. A
      preoperative cone beam CT and a mastoidectomy with a posterior tympanotomy were
      performed on four temporal bones. The optimal insertion axis was defined as the
      closest axis to the scala tympani centerline avoiding the facial nerve. A
      neuronavigation system, a robot assistance prototype, and software allowing a
      semi-automated alignment of the robot were used to align an insertion tool with
      an optimal insertion axis. Four procedures were performed and repeated three
      times in each temporal bone: manual, manual navigation-assisted, robot-based
      navigation-assisted, and robot-based semi-automated. The angle between the
      optimal and the insertion tool axis was measured in the four procedures. The
      error was 8.3 degrees  +/- 2.82 degrees  for the manual procedure (n = 24), 8.6
      degrees  +/- 2.83 degrees  for the manual navigation-assisted procedure (n = 24),
      5.4 degrees  +/- 3.91 degrees  for the robot-based navigation-assisted procedure
      (n = 24), and 3.4 degrees  +/- 1.56 degrees  for the robot-based semi-automated
      procedure (n = 12). A higher accuracy was observed with the semi-automated robot
      based technique than manual and manual navigation-assisted (p < 0.01).
      Combination of a navigation system and a manual insertion does not improve the
      alignment accuracy due to the lack of friendly user interface. On the contrary, a
      semi-automated robot-based system reduces both the error and the variability of
      the alignment with a defined optimal axis.

PMID- 27704280
TI  - Distinct conformers of transmissible misfolded SOD1 distinguish human SOD1-FALS
      from other forms of familial and sporadic ALS.
AB  - Evidence of misfolded wild-type superoxide dismutase 1 (SOD1) has been detected
      in spinal cords of sporadic ALS (sALS) patients, suggesting an etiological
      relationship to SOD1-associated familial ALS (fALS). Given that there are
      currently a number of promising therapies under development that target SOD1, it
      is of critical importance to better understand the role of misfolded SOD1 in
      sALS. We previously demonstrated the permissiveness of the G85R-SOD1:YFP mouse
      model for MND induction following injection with tissue homogenates from
      paralyzed transgenic mice expressing SOD1 mutations. This prompted us to examine
      whether WT SOD1 can self-propagate misfolding of the G85R-SOD1:YFP protein akin
      to what has been observed with mutant SOD1. Using the G85R-SOD1:YFP mice, we
      demonstrate that misfolded conformers of recombinant WT SOD1, produced in vitro,
      induce MND with a distinct inclusion pathology. Furthermore, the distinct
      pathology remains upon successive passages in the G85R-SOD1:YFP mice, strongly
      supporting the notion for conformation-dependent templated propagation and SOD1
      strains. To determine the presence of a similar misfolded WT SOD1 conformer in
      sALS tissue, we screened homogenates from patients diagnosed with sALS, fALS, and
      non-ALS disease in an organotypic spinal cord slice culture assay. Slice cultures
      from G85R-SOD1:YFP mice exposed to spinal homogenates from patients diagnosed
      with ALS caused by the A4V mutation in SOD1 developed robust inclusion pathology,
      whereas spinal homogenates from more than 30 sALS cases and various controls
      failed. These findings suggest that mutant SOD1 has prion-like attributes that do
      not extend to SOD1 in sALS tissues.

PMID- 27704283
TI  - Rewiring host activities for synthetic circuit production: a translation view.
AB  - The expression of synthetic circuits in host organisms, or chassis, is a key
      aspect of synthetic biology. Design adjustments made for maximal production may
      negatively affect the central metabolism and biosynthetic activities of the
      chassis host. Here, we review recent attempts to modulate synthetic circuit
      design for optimal production and present models that precisely capture the trade
      off between circuit production and chassis growth. We also present emerging
      concepts for full orthogonalization of synthetic productivity and its decoupling
      from the endogenous biosynthetic activities of the cell, opening new routes
      towards robust synthetic circuit expression.

PMID- 27704281
TI  - Mir-223 regulates the number and function of myeloid-derived suppressor cells in
      multiple sclerosis and experimental autoimmune encephalomyelitis.
AB  - Myeloid-derived cells play important modulatory and effector roles in multiple
      sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis
      (EAE). Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells,
      composed of monocytic (MO) and polymorphonuclear (PMN) fractions, which can
      suppress T cell activities in EAE. Their role in MS remains poorly characterized.
      We found decreased numbers of circulating MDSCs, driven by lower frequencies of
      the MO-MDSCs, and higher MDSC expression of microRNA miR-223 in MS versus healthy
      subjects. To gain mechanistic insights, we interrogated the EAE model. MiR-223
      knock out (miR-223-/-) mice developed less severe EAE with increased MDSC numbers
      in the spleen and spinal cord compared to littermate controls. MiR-223-/- MO
      MDSCs suppressed T cell proliferation and cytokine production in vitro and EAE in
      vivo more than wild-type MO-MDSCs. They also displayed an increased expression of
      critical mediators of MDSC suppressive function, Arginase-1(Arg1), and the signal
      transducer and activator of transcription 3 (Stat3), which herein, we demonstrate
      being an miR-223 target gene. Consistently, MDSCs from MS patients displayed
      decreased STAT3 and ARG1 expression compared with healthy controls, suggesting
      that circulating MDSCs in MS are not only reduced in numbers but also less
      suppressive. These results support a critical role for miR-223 in modulating MDSC
      biology in EAE and in MS and suggest potential novel therapeutic applications.

PMID- 27704284
TI  - Thoracic spine morphology of a pseudo-biped animal model (kangaroo) and
      comparisons with human and quadruped animals.
AB  - PURPOSE: Based on the structural anatomy, loading condition and range of motion
      (ROM), no quadruped animal has been shown to accurately mimic the structure and
      biomechanical function of the human spine. The objective of this study is to
      quantify the thoracic vertebrae geometry of the kangaroo, and compare with adult
      human, pig, sheep, and deer. METHODS: The thoracic vertebrae (T1-T12) from whole
      body CT scans of ten juvenile kangaroos (ages 11-14 months) were digitally
      reconstructed and geometric dimensions of the vertebral bodies, endplates,
      pedicles, spinal canal, processes, facets and intervertebral discs were recorded.
      Similar data available in the literature on the adult human, pig, sheep, and deer
      were compared to the kangaroo. A non-parametric trend analysis was performed.
      RESULTS: Thoracic vertebral dimensions of the juvenile kangaroo were found to be
      generally smaller than those of the adult human and quadruped animals. The most
      significant (p < 0.001) correlations (Rho) found between the human and kangaroo
      were in vertebrae and endplate dimensions (0.951 <= Rho <= 0.963), pedicles
      (0.851 <= Rho <= 0.951), and inter-facet heights (0.891 <= Rho <= 0.967). The
      deer displayed the least similar trends across vertebral levels. CONCLUSIONS:
      Similarities in thoracic spine vertebral geometry, particularly of the vertebrae,
      pedicles and facets may render the kangaroo a more clinically relevant human
      surrogate for testing spinal implants. The pseudo-biped kangaroo may also be a
      more suitable model for the human thoracic spine for simulating spine
      deformities, based on previously published similarities in biomechanical loading,
      posture and ROM.

PMID- 27704282
TI  - Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar
      degenerative diseases.
AB  - Changes in climbing fiber-Purkinje cell (CF-PC) synaptic connections have been
      found in the essential tremor (ET) cerebellum, and these changes are correlated
      with tremor severity. Whether these postmortem changes are specific to ET remains
      to be investigated. We assessed CF-PC synaptic pathology in the postmortem
      cerebellum across a range of degenerative movement disorders [10 Parkinson's
      disease (PD) cases, 10 multiple system atrophy (MSA) cases, 10 spinocerebellar
      ataxia type 1 (SCA1) cases, and 20 ET cases] and 25 controls. We observed
      differences in terms of CF pathological features across these disorders.
      Specifically, PD cases and ET cases both had more CFs extending into the parallel
      fiber (PF) territory, but ET cases had more complex branching and increased
      length of CFs in the PF territory along with decreased CF synaptic density
      compared to PD cases. MSA cases and SCA1 cases had the most severely reduced CF
      synaptic density and a marked paucity of CFs extending into the PF territory.
      Furthermore, CFs in a subset of MSA cases formed collateral branches parallel to
      the PC layer, a feature not seen in other diagnostic groups. Using unsupervised
      cluster analysis, the cases and controls could all be categorized into four
      clusters based on the CF pathology and features of PC pathology, including counts
      of PCs and their axonal torpedoes. ET cases and PD cases co-segregated into two
      clusters, whereas SCA1 cases and MSA cases formed another cluster, separate from
      the control cluster. Interestingly, the presence of resting tremor seemed to be
      the clinical feature that separated the cases into the two ET-PD clusters. In
      conclusion, our study demonstrates that these degenerative movement disorders
      seem to differ with respect to the pattern of CF synaptic pathology they exhibit.
      It remains to be determined how these differences contribute to the clinical
      presentations of these diseases.

PMID- 27704285
TI  - Cobb-1 versus cobb-to-cobb anterior fusion for adolescent idiopathic scoliosis
      Lenke 5C curves: a radiological comparative study.
AB  - PURPOSE: Anterior fusion is a well-established procedure for the treatment of
      Lenke 5C adolescent idiopathic scoliosis (AIS). This retrospective study aimed to
      assess preoperative and postoperative radiographic differences between the
      conventional anterior fusion and anterior short fusions (ASF) in Lenke 5C AIS.
      METHODS: Radiographic data of 42 consecutive cases of Lenke 5C AIS, which were
      surgically treated through anterior segmental fusion, were analyzed
      retrospectively. Patients have been divided into two groups: C group (n = 19)
      treated by the conventional fusion from the proximal end vertebra to the distal
      end vertebra of the main curve and C-1 group (n = 23) treated by ASF, sparing the
      lowest end vertebra of the main curve. Cobb angles of main curve, apical vertebra
      tilt, C7 coronal tilt, lowest instrumented vertebra angle (LIV angle), LIV
      adjacent level disc angulation (LIVDA), and the first uninstrumented vertebra
      angle (FUV angle) were measured on anteroposterior radiographs of the entire
      spine. LIVDA, FUV wedging, and rotation were measured on stretch films. C7
      sagittal tilt, lumbar lordosis, thoracic kyphosis, and proximal kyphosis junction
      were measured on lateral radiographs of the entire spine. Repeated-measures
      analysis of variance and fisher test were used for the statistical analysis.
      RESULTS: The preoperative main curve was 39.9 +/- 9.1 degrees  in the C group vs.
      (versus) 42.8 +/- 11.8 degrees  in the C-1 group. At a mean follow-up of 26.2
      months (range 10.5-66.3 months), postoperative main curve improved of 75.8 +/-
      21.2 % (10.4 +/- 9.2 degrees , p < 0.001) in the C group and of 52.7 +/- 18.7 %
      (20.1 +/- 8.1 degrees , p < 0.001) in the C-1 group. All parameters improved
      except the LIVDA, which was slightly impaired, especially in the C-1 group with
      5.6 +/- 4.2 degrees  vs. 4.4 +/- 2.2 degrees  in the C group. On stretch films,
      FUV rotation was the only parameter to differ; it was graded at 1 +/- 0.7 in the
      C-1 group vs. 0.6 +/- 0.5 in the C group (p = 0.04). No disk obliquity just under
      the future instrumentation and equivalent FUV wedging were found in any of the
      two groups. CONCLUSIONS: The conventional anterior fusion and ASF give equivalent
      correction in Lenke 5C AIS, but ASF seems to induce adding-on of the disk below
      the LIV. FUV rotation on stretch films does not seem to be a predictive factor of
      postoperative radiological outcome.

PMID- 27704287
TI  - In Response to: "Single Versus Multiple Hyperbaric Sessions for Carbon Monoxide
      Poisoning in a Murine Model".

PMID- 27704288
TI  - Letter to the Editor Regarding: Patterns and Impact of Hypoglycemia,
      Hyperglycemia, and Glucose Variability on Inpatients with Insulin-Treated Cystic
      Fibrosis-Related Diabetes.

PMID- 27704286
TI  - Herniectomy versus herniectomy with the DIAM spinal stabilization system in
      patients with sciatica and concomitant low back pain: results of a prospective
      randomized controlled multicenter trial.
AB  - PURPOSE: To investigate the short and medium term efficacy and patient outcomes
      of DIAM spinal stabilization system on back pain, disability, leg pain and
      quality of life. METHODS: 165 patients were enrolled; 146 patients with a single
      level disc herniation (L2 to L5) were randomized: 75 investigational (herniectomy
      and DIAM) and 71 control (herniectomy alone) treated and followed up for 24
      months. RESULTS: Significant improvements overtime (P < 0.001) in both groups but
      not significantly different between groups for visual analog scale (VAS) back
      pain at 6 months (investigational -3.97 +/- 2.55 vs control-3.37 +/- 3.15, P =
      0.228) and Oswestry Disability Index (ODI) at 12 months (-38.55 +/- 20.10 vs 
      37.19 +/- 22.61, P = 0.719). For both outcomes, there was no statistically
      significant difference between the groups, at all postoperative time points.
      Although the enrolment ended before the intended sample size (308 patients) was
      reached, the number of patients reaching the VAS back pain minimally clinically
      important difference (MCID) of >=2.2 at 6 months was higher in the
      investigational (79.4 % vs control 57.1 %, P = 0.008). These results were
      sustained throughout 24 months (82.8 vs 64.4 %, P < 0.05). In average, surgical
      duration (P < 0.001), blood loss (P = 0.029) and skin incision (P < 0.001) in the
      investigational were 10 min longer, 22.5 ml greater and 2.0 cm wider than control
      group (median values). Improved tertiary outcomes from BL to 24 mo in both groups
      (investigational vs control): VAS leg pain (mean decrease -6.41 +/- 2.57 to -6.41
      vs -5.61 +/- to -3.30); improved quality of life (SF-36: 20.68 +/- 9.44 vs 16.90
      +/- 10.74); pain medication reduction: 56.7 vs 47.9 %; return to work: 45.7 vs
      38.0 %. Adverse event rates: 68.5 % investigational and 66.2 % control.
      CONCLUSIONS: This is the first randomized controlled trial to report equivalent
      efficacy and safety of herniectomy with or without DIAM spinal stabilizing
      device. Leg pain, back pain and the level of disability were not significantly
      different between groups; however, number of patients reaching the MCID for back
      pain was significantly higher in the investigational group at 6 through 24
      months.

PMID- 27704289
TI  - Preadmission schooling context helps to predict examination performance
      throughout medical school.
AB  - This study investigates the effects of socioeconomic status and schooling on the
      academic attainment of a cohort of students at a single medical school (N = 240).
      Partial least squares structural equation modelling was used to explore how
      students' summative assessment scores over 4 years of medical school were
      affected by: attainment in secondary school examinations (GCSEs and A-levels);
      the Income Deprivation Affecting Children Index (IDACI) rank associated with
      students' home postcodes; the performance of students' A-level institutions,
      measured as the percentage of A-level students achieving 3 A-levels at AAB or
      higher in two or more facilitating subjects. The effects were consistent across
      time; the final linear regression model used students' cumulative scores (the
      basis of the medical school's UK Foundation Programme submission) as the
      dependent variable. The final model fit was quite poor (R2 = .184, n = 178).
      IDACI Rank was non-significant and excluded from the final model. Both GCSE
      (.340, p < .001) and A-level (.204, p < .005) scores were associated with
      increasing Cumulative Score; School Performance was associated with decreasing
      Cumulative Score (-.159, p < .05). This study confirmed the predictive validity
      of prior academic attainment and found the same inverse relationship between
      schooling and medical course performance as previous studies. The study found no
      evidence that socioeconomic background affects course performance; however,
      students admitted to medicine from poorly performing schools achieve higher
      academic attainment throughout the course than students admitted from better
      performing schools with the same grades. Schooling could be taken into account
      for admissions purposes.

PMID- 27704290
TI  - Do personality traits assessed on medical school admission predict exit
      performance? A UK-wide longitudinal cohort study.
AB  - Traditional methods of assessing personality traits in medical school selection
      have been heavily criticised. To address this at the point of selection, "non
      cognitive" tests were included in the UK Clinical Aptitude Test, the most widely
      used aptitude test in UK medical education (UKCAT: http://www.ukcat.ac.uk/ ). We
      examined the predictive validity of these non-cognitive traits with performance
      during and on exit from medical school. We sampled all students graduating in
      2013 from the 30 UKCAT consortium medical schools. Analysis included: candidate
      demographics, UKCAT non-cognitive scores, medical school performance data-the
      Educational Performance Measure (EPM) and national exit situational judgement
      test (SJT) outcomes. We examined the relationships between these variables and
      SJT and EPM scores. Multilevel modelling was used to assess the relationships
      adjusting for confounders. The 3343 students who had taken the UKCAT non
      cognitive tests and had both EPM and SJT data were entered into the analysis.
      There were four types of non-cognitive test: (1) libertariancommunitarian, (2)
      NACE-narcissism, aloofness, confidence and empathy, (3) MEARS-self-esteem,
      optimism, control, self-discipline, emotional-nondefensiveness (END) and faking,
      (4) an abridged version of 1 and 2 combined. Multilevel regression showed that,
      after correcting for demographic factors, END predicted SJT and EPM decile.
      Aloofness and empathy in NACE were predictive of SJT score. This is the first
      large-scale study examining the relationship between performance on non-cognitive
      selection tests and medical school exit assessments. The predictive validity of
      these tests was limited, and the relationships revealed do not fit neatly with
      theoretical expectations. This study does not support their use in selection.

PMID- 27704291
TI  - Dynamic measures of skeletal muscle dialysate and plasma amino acid concentration
      in response to exercise and nutrient ingestion in healthy adult males.
AB  - Nutrient stimulation of muscle protein synthesis (MPS) is regulated by the change
      in extracellular essential amino acid (EAA) concentration. In vivo microdialysis
      (MD) is a minimally invasive sampling technique, capable of sampling solute in
      the interstitial space of a target tissue. In a contralateral limb design (REST
      vs. EX), this study utilised in vivo MD to examine the change in skeletal muscle
      dialysate amino acid concentration following ingestion of whey protein isolate
      (WPI) and flavoured water (CON). Four male subjects undertook unilateral,
      concentric lower limb knee extensor resistance exercise (RE) on two occasions.
      After RE, an MD catheter (CMA 63) was inserted into m. vastus lateralis of the
      exercise and resting leg and sampled serially over 7 h. Following a 2.5 h
      equilibration period subjects consumed either 0.55 g/kg WPI or CON. Peak plasma
      EAA (2656 +/- 152 uM) preceded the peak in dialysate EAA (2345 +/- 164 uM) by 30
      min in response to WPI ingestion; however, the post-prandial elevation in
      dialysate EAA extended beyond that of the plasma. This resulted in no difference
      in the dialysate EAA area under the curve (DeltaAUC270) relative to plasma in
      response to WPI ingestion [220 +/- 29 vs. 206 +/- 7.9 mmol min/L (p = 0.700)]. A
      bout of unilateral lower limb RE had no effect of the subsequent dialysate amino
      acid concentration in response to either WPI or CON ingestion. These data
      represent a novel report describing the time course and magnitude of change in
      skeletal muscle dialysate concentration of key nutrient regulators of MPS sampled
      by in vivo MD, in response to nutrient ingestion with and without RE.

PMID- 27704292
TI  - A population-specific correlation between ADIPOQ rs2241766 and rs 1501299 and
      colorectal cancer risk: a meta-analysis for debate.
AB  - AIMS: Many epidemiological studies have investigated the correlation between
      adiponectin, C1Q and collagen domain containing (ADIPOQ) single nucleotide
      polymorphisms (SNPs) and risk of colorectal cancer (CRC). Although conflicting
      results have been reported, there was dispute regarding two SNPs (rs2241766 T/G
      and rs1501299 G/T). Therefore, we conducted a meta-analysis to systematically
      assess the associations and try to find the reasons for the dispute. METHODS: We
      searched PubMed, the Cochrane Library, Elsevier, Wiley Online Library, China
      National Knowledge Infrastructure, WanFang data and Chongqing VIP to search for
      all eligible case-control studies published up to January 2015. Effect sizes of
      odds ratios (OR) and 95 % confidence intervals (95 % CI) were calculated using a
      fixed- or random-effect model. RESULTS: Ten case-control studies including 4377
      cases and 5584 controls were selected. A significant difference was observed in
      Chinese (OR 0.76; 95 % CI 0.68, 0.85; P < 0.001) and Ashkenazi Jewish populations
      (OR 0.79; 95 % CI 0.63, 0.99; P = 0.04) for rs2241766 with dominant model (TT vs
      TG + GG). A significant difference was observed in the Chinese population (OR
      1.23; 95 % CI 1.11, 1.37; P < 0.001) for rs1501299 with dominant model (TT vs TG
      + GG). In addition, intake of red meat showed a synergistic effect between ADIPOQ
      gene and risk of colorectal cancer (CRC). CONCLUSIONS: ADIPOQ SNPs rs2241766 T/G
      and rs 1501299 G/T have a population-specific correlation with risk of CRC.
      However, small sample studies may increase reporting bias, particularly if the
      total number of studies included in the analysis is small.

PMID- 27704293
TI  - Sensory Responsiveness in Siblings of Children with Autism Spectrum Disorders.
AB  - This study examined sensory responsiveness in unaffected siblings of children
      with autism spectrum disorder (ASD) and associations between sensory
      responsiveness and social severity. Sensory Profile Caregiver Questionnaires and
      Social Responsiveness Scales were completed by parents of 185 children between
      age 4 and 10.95 years. Significant differences were found between participants
      with ASD and controls, and between participants with ASD and unaffected siblings
      for all sensory quadrants and domains, but not between controls and unaffected
      siblings. Social responsiveness scores were significantly correlated with scores
      from most sensory profile categories. Sensory responsiveness as an endophenotype
      of ASD is not indicated from these findings; however, studies with larger numbers
      of unaffected siblings and controls are needed to confirm the null hypothesis.

PMID- 27704294
TI  - Brief Report: Which Came First? Exploring Crossmodal Temporal Order Judgements
      and Their Relationship with Sensory Reactivity in Autism and Neurotypicals.
AB  - Previous studies have indicated that visual-auditory temporal acuity is reduced
      in children with autism spectrum conditions (ASC) in comparison to neurotypicals.
      In the present study we investigated temporal acuity for all possible bimodal
      pairings of visual, tactile and auditory information in adults with ASC (n = 18)
      and a matched control group (n = 18). No group differences in temporal acuity for
      crossmodal stimuli were observed, suggesting that this may be typical in adults
      with ASC. However, visual-tactile temporal acuity and bias towards vision when
      presented with visual-auditory information were both predictors of self-reported
      sensory reactivity. This suggests that reduced multisensory temporal acuity
      and/or attention towards vision may contribute to atypical sensory reactivity.

PMID- 27704295
TI  - Do CAD/CAM dentures really release less monomer than conventional dentures?
AB  - OBJECTIVES: Computer-aided design (CAD)/computer-aided manufacturing (CAM)
      dentures are assumed to have more favourable material properties than
      conventionally fabricated dentures, among them a lower methacrylate monomer
      release. The aim of this study was to test this hypothesis. MATERIALS AND
      METHODS: CAD/CAM dentures were generated from ten different master casts by using
      four different CAD/CAM systems. Conventional, heat-polymerised dentures served as
      control group. Denture weight and volume were measured; the density was
      calculated, and the denture surface area was assessed digitally. The monomer
      release after 7 days of water storage was measured by high-performance liquid
      chromatography. RESULTS: Whole You Nexteeth and Wieland Digital Dentures had
      significantly lower mean volume and weight than conventional dentures. Baltic
      Denture System and Whole You Nexteeth had a significantly increased density.
      Baltic Denture System had a significantly smaller surface area. None of the
      CAD/CAM dentures released significantly less monomer than the control group.
      CONCLUSIONS: All tested dentures released very low amounts of methacrylate
      monomer, but not significantly less than conventional dentures. A statistically
      significant difference might nevertheless exist in comparison to other, less
      recommendable denture base materials, such as the frequently used
      autopolymerising resins. CLINICAL RELEVANCE: CAD/CAM denture fabrication has
      numerous advantages. It enables the fabrication of dentures with lower resin
      volume and lower denture weight. Both could increase the patient comfort.
      Dentures with higher density might exhibit more favourable mechanical properties.
      The hypothesis that CAD/CAM dentures release less monomer than conventional
      dentures could, however, not be verified.

PMID- 27704296
TI  - Photodynamic therapy decrease immune-inflammatory mediators levels during
      periodontal maintenance.
AB  - Antimicrobial photodynamic therapy (aPDT) was introduced as a promising adjuvant
      therapy on the periodontal treatment. The aim of this study was to evaluate the
      effect of aPDT on inflammatory mediator levels in residual periodontal pockets of
      patients with severe chronic periodontitis under periodontal maintenance, during
      12 months follow-up. A randomized controlled trial study was conducted in 28
      patients with severe chronic periodontitis. After non-surgical periodontal
      treatment, patients with at least four teeth with residual pocket probing depth
      (PPD) >=4 mm were randomly assigned to either aPDT or control group. The aPDT
      (low power laser: 660 nm, 40 mW, 90 J/cm2, methylene blue 0.01 %) was performed
      at baseline and 3, 6, and 9 months. Clinical parameters were collected before and
      3 and 12 months after the intervention, and gingival crevicular fluid was
      collected in the same times, including 1 week after the intervention.
      Immunological evaluation was carried out using the Luminex assay which quantified
      the expression of ten cytokines: interleukin (IL)-1alpha, IL-1beta, IL-8, IL-1ra,
      fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF),
      interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-4, and IL-10. All
      clinical variables showed significant improvement for both groups, but there was
      no statistical difference between groups with no clinical benefits. IL-1alpha, IL
      1beta, IL-8, and VEGF showed significant differences (p < 0.05) between groups,
      whereas IL-1ra mediators, IFN-gamma, and IL-10 demonstrated a statistical
      difference (p < 0.01) over time in the same group. At any time, FGF, IL-4, and
      TNF-alpha showed no statistical difference between groups (p > 0.05). aPDT
      therapy can improve the benefits on inflammation control during the periodontal
      maintenance.

PMID- 27704297
TI  - A large survey among European trainees in clinical microbiology and infectious
      disease on training systems and training adequacy: identifying the gaps and
      suggesting improvements.
AB  - The purpose of this investigation was to perform a survey among European clinical
      microbiology (CM) and infectious disease (ID) trainees on training satisfaction,
      training tools, and competency assessment. An online, anonymous survey in the
      English language was carried out between April and July 2015. There were 25
      questions: seven in a 5-point Likert scale (1: worst scenario, 5: best scenario)
      and the remainder as closed multiple-choice questions in five areas
      (satisfaction, adequacy, system, mentorship, and evaluation of training).
      Included were 419 respondents (215 CM, 159 ID, and 45 combined CM/ID) from 31
      European countries [mean age (standard deviation) 32.4 (5.3) years, 65.9 %
      women]. Regarding satisfaction on the training scheme, CM and ID scored 3.6 (0.9)
      and 3.2 (1.0), respectively. These scores varied between countries, ranging from
      2.5 (1.0) for Italian ID to 4.3 (0.8) for Danish CM trainees. The majority of
      respondents considered training in management and health economics inadequate and
      e-learning and continuing medical education programs insufficient. Many trainees
      (65.3 % of CM and 62.9 % of ID) would like to have more opportunities to spend a
      part of their training abroad and expected their mentor to be more involved in
      helping with future career plans (63.5 % of CM and 53.4 % of ID) and practical
      skills (53.0 % of CM and 61.2 % of ID). Two-thirds of the respondents across the
      specialties agreed that a European exam should be developed, but half of them
      thought it should not be made mandatory. This survey shows high heterogeneity in
      training conditions in European countries, identifies perceived gaps in training,
      and suggests areas for improvements.

PMID- 27704298
TI  - Sequential formation of two branched intermediates during protein splicing of
      class three inteins.
AB  - Inteins are the protein equivalent of introns. They are seamlessly removed during
      post-translational maturation of their host protein (extein). Inteins from
      extremophiles played a key role in understanding intein-mediated protein
      splicing. There are currently three classes of inteins defined by catalytic
      mechanism and sequence signatures. This study demonstrates splicing of three
      class 3 mini-inteins: Burkholderia vietnamiensis G4 Bvi IcmO intein,
      Mycobacterium smegmatis MC2 155 Msm DnaB-1 intein and Mycobacterium leprae strain
      TN Mle DnaB intein. B. vietnamiensis has a broad ecological range and remediates
      trichloroethene. M. smegmatis is a biofilm forming soil bacteria. Although other
      intein classes have only a single branched intermediate at the C-terminal splice
      junction, the class 3 intein reaction pathway includes two branched
      intermediates. The class 3 specific branched intermediate is formed by an
      internal cysteine, while the C-terminal branch intermediate is at a serine or
      threonine in all class 3 inteins except the Bvi IcmO intein, where it is a
      cysteine. This latter cysteine was unable to compensate for mutation of the class
      3-specific internal catalytic cysteine despite the Bvi IcmO intein having an N
      terminal splice junction naturally tuned for a cysteine nucleophile,
      demonstrating the mandatory order of branch intermediates in class 3 inteins.

PMID- 27704299
TI  - Child Abuse and Psychiatric Co-morbidity Among Chinese Adolescents: Emotional
      Processing as Mediator and PTSD from Past Trauma as Moderator.
AB  - This study investigated whether child abuse was associated with psychiatric co
      morbidity in a group of Chinese adolescents, and whether this association would
      be mediated by emotional processing difficulties and moderated by the severity of
      PTSD from other traumas in the past. Four hundred seventy-four adolescents
      participated in the study. They completed the Childhood Trauma Questionnaire
      Short Form, General Health Questionnaire-28, the Posttraumatic Stress Diagnostic
      Scale, and Emotional processing scale-25. The results showed that after adjusting
      for the total number of traumatic events and how long ago the most traumatic
      event occurred, child abuse was associated with psychiatric co-morbidity. This
      association was not moderated by the severity of PTSD from past traumas but
      mediated by emotion processing difficulties. To conclude, adolescents who
      experience child abuse can develop emotional processing difficulties which in
      turn impact on psychiatric symptoms. Experience of past trauma does not influence
      these psychological processes.

PMID- 27704300
TI  - Forward Genetic Screening Using Behavioral Tests in Zebrafish: A Proof of Concept
      Analysis of Mutants.
AB  - The zebrafish enjoys several advantages over other model organisms. It is small,
      easy to maintain, prolific, and numerous genetic tools are available for it. For
      example, forward genetic screens have allowed investigators to identify important
      genes potentially involved in a variety of functions from embryogenesis to
      cancer. However, despite its sophisticated behavioral repertoire, behavioral
      methods have rarely been utilized in forward genetic screens. Here, we employ a
      two-tiered strategy, a proof of concept study, to explore the feasibility of
      behavioral screens. We generated mutant lines using transposon-based insertional
      mutagenesis, allowing us to bias mutant selection with target genes expressed
      within the brain. Furthermore, we employed an efficient and fast behavioral pre
      selection in which we investigated the locomotory response of 5-day post
      fertilization old larval fish to hyperosmotic shock. Based on this assay, we
      selected five lines for our lower throughput secondary adult behavioral screen.
      The latter screen utilized tests in which computer animated image presentation
      and video-tracking-based automated quantification of behavior allowed us to
      compare heterozygous zebrafish with their wild-type siblings on their responses
      to a variety of stimuli. We found significant mutation induced adult behavioral
      alterations in 4 out of the 5 lines analyzed, including changes in response to
      social or fear inducing stimuli, to handling and novelty, or in habituation to
      novelty. We discuss the pros and cons of behavioral phenotyping and of the use of
      different forward genetic methods in biomedical research with zebrafish.

PMID- 27704302
TI  - Longitudinal Relationships between Bullying and Moral Disengagement among
      Adolescents.
AB  - Moral disengagement is a series of cognitive processes used to disengage moral
      standards to achieve absolved guilt and permit immoral conduct and has been found
      to be an important connection to bullying and aggressive behaviors among
      adolescents. This study examined the longitudinal relationship between moral
      disengagement and bullying behavior among a group of adolescents from fifth grade
      to ninth grade (n = 1180, mean age = 12.2, SD = 1.29, 46.5 % female, 80.2 %
      Caucasian/White, 7.1 % Black/African American, 5.4 % Latino/Hispanic, 2.4 % Asian
      American, and 1.7 % other) over three semesters. The objectives were to
      investigate (a) whether moral disengagement was a precursor to bullying behavior,
      vice versa, or whether the relationship was reciprocal and (b) whether gender and
      grade predicted moral disengagement and bullying behavior. The results showed
      that moral disengagement predicted bullying perpetration 6 months later. Also,
      older students and males utilized more moral disengagement than younger students
      and females and younger students and males engaged in greater bullying
      perpetration. Indirect paths linking gender and grade to bullying via moral
      disengagement at previous time points were identified and implications for
      bullying prevention are discussed. The findings underscore the importance of
      examining moral disengagement when studying bullying and across gender and
      development.

PMID- 27704304
TI  - Adherence to ACIP Recommendation for Human Papillomavirus Vaccine Among US
      Adolescent Girls.
AB  - The objective of this study was to examine correlates of human papillomavirus
      (HPV) vaccine use according to Advisory Committee on Immunization Practices
      (ACIP)'s recommendations among US adolescent girls. We used National Immunization
      Survey of Teens 2013 data. Based on provider-verified (n = 9403) information,
      57.3, 39.1 and 19.0 % of adolescent girls, initiated, completed and completed the
      HPV vaccine according to ACIP's recommendation (by age 12), respectively.
      Hispanic race/ethnicity, a physician recommendation for HPV vaccine and >=1
      influenza vaccine in the past 3 years were all associated with a higher
      likelihood of compliance with ACIP's recommendation. Girls from a larger family
      and those whose immunization provider was a STD/school/teen clinic were less
      likely to receive the vaccine at the recommended age compared to a girl raised in
      a smaller sized family and received immunization from a hospital facility,
      respectively. Only one-fifth of 13-17 yo girls receive the HPV vaccine by age 12
      as recommended by ACIP. Physician visits and influenza vaccination settings are
      opportunities to improve vaccine series completion at the recommended age.

PMID- 27704301
TI  - Genetic and Genomic Response to Selection for Food Consumption in Drosophila
      melanogaster.
AB  - Food consumption is an essential component of animal fitness; however, excessive
      food intake in humans increases risk for many diseases. The roles of
      neuroendocrine feedback loops, food sensing modalities, and physiological state
      in regulating food intake are well understood, but not the genetic basis
      underlying variation in food consumption. Here, we applied ten generations of
      artificial selection for high and low food consumption in replicate populations
      of Drosophila melanogaster. The phenotypic response to selection was highly
      asymmetric, with significant responses only for increased food consumption and
      minimal correlated responses in body mass and composition. We assessed the
      molecular correlates of selection responses by DNA and RNA sequencing of the
      selection lines. The high and low selection lines had variants with significantly
      divergent allele frequencies within or near 2081 genes and 3526 differentially
      expressed genes in one or both sexes. A total of 519 genes were both genetically
      divergent and differentially expressed between the divergent selection lines. We
      performed functional analyses of the effects of RNAi suppression of gene
      expression and induced mutations for 27 of these candidate genes that have human
      orthologs and the strongest statistical support, and confirmed that 25 (93 %)
      affected the mean and/or variance of food consumption.

PMID- 27704306
TI  - RETRACTED ARTICLE: Peroxidase Gene-Based Estimation of Genetic Relationships and
      Population Structure Among Wild Pistacia Species Populations.

PMID- 27704305
TI  - Health-related quality of life in patients with serious non-specific symptoms
      undergoing evaluation for possible cancer and their experience during the
      process: a mixed methods study.
AB  - PURPOSE: The purpose of this research was to measure changes in HRQoL during the
      diagnostic evaluation of patients presenting with non-specific symptoms possibly
      attributable to cancer, to describe their experiences of HRQoL and to merge these
      findings with intent to obtain a more comprehensive understanding of their HRQoL
      experience during this stressful life event. METHODS: A convergent mixed methods
      (MM) design was used and involved quantitative data about HRQoL measured by the
      EORTC-QLQ-C30 instrument and qualitative interview data about patients' HRQoL
      experiences. Participants completed the EORTC-QLQ-C30 questionnaire prior to and
      after evaluation. The baseline questionnaire informed the purposive sampling for
      the qualitative interview study, and open-end questions matched to the EORTC-QLQ
      C30 constructs were used in the semi-structured interviews. RESULTS: A total of
      838 patients were enrolled in the quantitative study; 680 (81 %) also completed
      follow-up. Twenty-one patients participated in interviews. The MM findings are
      the meta-inferences drawn by looking across the matched quantitative and
      qualitative findings: physical function, social function, role function,
      emotional function, cognitive function, social function, symptoms and quality of
      life. CONCLUSION: The survey results illustrate that HRQoL improved over time and
      the qualitative findings confirmed and further expanded the survey results. The
      MM analysis underlines that the HRQoL experience cannot be observed independently
      from context. Participants adapted to their situation over time, and this may
      change their perceptions of HRQoL. These findings can be used to enhance evidence
      based care as clinicians need to be aware of how the context influences the HRQoL
      experience.

PMID- 27704307
TI  - Association of the Common Catalase Gene Polymorphism rs1001179 With Glycated
      Hemoglobin and Plasma Lipids in Hyperlipidemic Patients.
AB  - Catalase represents perhaps the most effective antioxidant defense in the body
      under conditions of increased oxidative stress, and rs1001179 (CAT-262C >T) is
      its most extensively studied gene polymorphism. Using an established PCR-RFLP
      method for genotyping, we examined the association of rs1001179 with glycated
      hemoglobin (HbA1c) and plasma lipids using univariate analyses with age, sex,
      body mass index (BMI), smoking, and alcohol abuse as covariates, in a group of
      dyslipidemic patients from northern Greece. Our results suggest that the TT
      genotype is a risk factor for increased HbA1c and plasma triglycerides, and that
      this association is modulated by the BMI and/or age of the patients.

PMID- 27704310
TI  - Role of Leptin and SOCS3 in Inhibiting the Type I Interferon Response During
      Obesity.
AB  - Obesity provokes an imbalance in the immune system, including an aberrant type I
      interferon response during some viral infections and after TLR stimulation. SOCS3
      overexpression and altered systemic leptin levels could be responsible for the
      reduced type I interferon production in people with obesity and, eventually,
      significantly increase the risk of viral infection. The aim of this study was to
      determine whether SOCS3- and leptin-induced tolerance are responsible for the
      reduced type I interferon production in people with obesity. SOCS3 overexpression
      in PBMCs from people with obesity was inhibited with the small interfering RNA
      (siRNA) assay, and leptin-induced tolerance was evaluated in PBMCs from non-obese
      volunte?ers and U937 cells treated with TLR ligands. SOCS3, but not SOCS1, gene
      silencing via siRNA increased the type I interferon response in PBMCs obtained
      from people with obesity. On the other hand, leptin induced SOCS3 expression and
      inhibited type I interferons in PBMCs from healthy donors and in U937 monocytes
      stimulated with TLR ligands. Taken together, these results demonstrate that
      reduced type I interferon production in obesity is caused by SOCS3 overexpression
      as well as tolerance induced by leptin. Here, we demonstrate a key role of leptin
      and SOCS3 in inhibiting the type I interferon response during obesity.

PMID- 27704308
TI  - Toxicants in folk remedies: implications of elevated blood lead in an American
      born infant due to imported diaper powder.
AB  - Though most childhood lead exposure in the USA results from ingestion of lead
      based paint dust, non-paint sources are increasingly implicated. We present
      interdisciplinary findings from and policy implications of a case of elevated
      blood lead (13-18 mcg/dL, reference level <5 mcg/dL) in a 9-month-old infant,
      linked to a non-commercial Malaysian folk diaper powder. Analyses showed the
      powder contains 62 % lead by weight (primarily lead oxide) and elevated antimony
      [1000 parts per million (ppm)], arsenic (55 ppm), bismuth (110 ppm), and thallium
      (31 ppm). These metals are highly bioaccessible in simulated gastric fluids, but
      only slightly bioaccessible in simulated lung fluids and simulated urine,
      suggesting that the primary lead exposure routes were ingestion via hand-mouth
      transmission and ingestion of inhaled dusts cleared from the respiratory tract.
      Four weeks after discontinuing use of the powder, the infant's venous blood lead
      level was 8 mcg/dL. Unregulated, imported folk remedies can be a source of
      toxicant exposure. Additional research on import policy, product regulation,
      public health surveillance, and culturally sensitive risk communication is needed
      to develop efficacious risk reduction strategies in the USA. The more widespread
      use of contaminated folk remedies in the countries from which they originate is a
      substantial concern.

PMID- 27704311
TI  - Transcriptome analysis of the gonads of olive flounder (Paralichthys olivaceus).
AB  - Olive flounder (Paralichthys olivaceus) is an economically important cultured
      marine fish in China, Korea, and Japan. Controlling and managing the breeding of
      olive flounder in captivity is an imperative step toward obtaining a sustainable
      supply of this fish in aquaculture production systems. Therefore, investigation
      on the molecular regulatory mechanism of gonadal development and gametogenesis in
      this species is of great significance in aquaculture. Furthermore, identification
      of the expression profile of numerous sex-related genes is the first step to
      primarily understand such molecular regulatory mechanism. Six female and six male
      gonads obtained from 2-year-old olive flounders were sequenced using Illumina,
      which produced 6.68 and 6.24 GB data for ovary and testis, respectively. The
      reads were mapped to the draft genome of olive flounder, and then the reads per
      kilobase per million (FPKM) for each gene were calculated. The female-/male
      biased expressed genes were investigated based on the FPKM values. Overall, 3086
      female-biased and 5048 male-biased genes were screened out. GO enrichment
      analysis showed that the GO terms "male meiosis," "gamete generation,"
      "fertilization," "spermatogenesis," and "germ plasma" were enriched in male
      biased genes. In addition, the GO terms "cell morphogenesis involved in
      differentiation," "embryonic morphogenesis," "plasma membrane," "steroid hormone
      receptor activity," and "aromatase activity" were enriched in female-biased
      genes. Moreover, 373,369 single nucleotide polymorphisms and 32,993 indels were
      identified in the transcriptome. This work is the largest collection of gonad
      transcriptome data for olive flounder and provides an extensive resource for
      future gonadal development and gametogenesis molecular biology studies in this
      species.

PMID- 27704312
TI  - Prediction of Antiphospholipid syndrome using Annexin A5 competition assay in
      patients with SLE.
AB  - A significantly high correlation between reduced activity of Annexin A5 by the
      flow cytometric assay (FCA) and the diagnosis of antiphospholipid syndrome (APS)
      has been reported. The aim of this study was to assess the clinical and
      laboratory significance of the Annexin A5 competition assay among patients with
      systemic lupus erythematosus (SLE). The FCA competition assay was performed on
      blood samples from 57 consecutive SLE patients. The FCA was performed according
      to a previously validated method. Forty-seven patients (82.5 %) had SLE without
      APS and ten (17.5 %) had SLE with APS. Twenty-four (42 %) of the patients had
      mean levels of AnxA5 fluorescence below the mean and standard deviation of the
      controls and were considered positive. SLE patients with a positive FCA were
      found to have an increased risk for a hypercoagulable or vascular state (86 % of
      the patients had cerebrovascular disease, 89 % had Raynaud's phenomenon, and 80 %
      had deep vein thrombosis). The risk for any hypercoagulable or vascular state was
      significantly increased (P = 0.012, RR-2.3, 95 % CI 1.4-3.8). A positive FCA
      assay was found in 90 % of the patients with APS (P < 0.001), with a sensitivity
      of 90 % and a specificity of 68 % for this diagnosis. The positive and negative
      predictive values were 0.4 and 0.97, respectively. Correlations were found
      between positive FCA and positive Anti-Cardiolipin antibody (P < 0.001), and Anti
      beta2 glycoprotein I levels (P = 0.013). Our findings suggest that the FCA is a
      practical assay for the detection of clinically relevant APS among patients with
      SLE.

PMID- 27704313
TI  - The effect of etanercept on traditional metabolic risk factors for cardiovascular
      disease in patients with rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis (RA) are at an increased risk of
      cardiovascular disease (CVD). Treatment with tumor necrosis factor inhibitors
      improves both joint symptoms associated with RA and also CVD risk. This
      exploratory analysis of a phase 4 study evaluated changes in metabolic risk
      factors in patients with RA treated with etanercept. Metabolic analytes were
      measured at baseline, week 12, and week 24 in patients enrolled in a randomized,
      double-blind, placebo-controlled study to evaluate the efficacy and safety of
      etanercept in moderately active RA. Patients received either placebo or
      etanercept 50 mg every week (QW) for 12 weeks, after which all patients received
      etanercept 50 mg QW through week 24. Levels of metabolic analytes were assessed
      in all patients, including patients with diabetes and hyperlipidemia, and
      described descriptively. A total of 210 patients were randomized, 104 to placebo
      and 106 to etanercept. There were no significant changes in metabolic risk
      factors from baseline to week 12 or 24 in all patients. Levels of metabolic
      analytes were similar in patients with diabetes and hyperlipidemia, with some
      exceptions; fasting glucose and fasting insulin decreased through week 12, and
      hemoglobin A1C decreased slightly through week 24 in patients with diabetes.
      Treatment with etanercept did not adversely affect levels of metabolic risk
      factors for CVD in patients with RA.

PMID- 27704314
TI  - Ontogenetic Changes in Azoxyglycoside Levels in the Leaves of Dioon edule Lindl.
AB  - Plants have multiple strategies, including phytochemicals that protect their
      vulnerable tissues against pathogens and herbivores. Dioon edule, like all
      cycads, possess unique azoxy-type compounds, azoxyglycosides (AZGs) as a chemical
      defense; however, the ontogenetic variability of these compounds in this long
      lived cycad is unknown. Here, we investigated the effects of plant age, sex,
      genotype and individual heterozygosity on AZG levels in mature leaves of wild D.
      edule populations from eastern Mexico. Individuals were divided into three
      ontogenetic stages: seedlings, juveniles and adults. We established overall leaf
      quality by quantifying pigments associated with photosynthesis; chlorophylla,
      chlorophyllb and lutein. Leaf chlorophylla levels were higher in seedlings
      compared to adult cycads. Plants were genotyped using 11 microsatellite markers
      and foliar AZG levels were quantified by HPLC. AZG levels do not correlate with
      plant genotype or the individual's heterozygosity. Genetic analysis identified a
      distinction between lowland and highland individuals; foliar AZG levels were
      higher in lowland adult cycads compared to highland individuals. In both
      populations, the highest AZG levels were found in seedlings compared to adult
      cycads. These young cycads are highly reliant on their few leaves since seedlings
      bear one or two leaves for the first years of their life and, thus, are unlikely
      to recover from defoliation. The results suggest that cycad leaves with a greater
      nutritive content and a higher value for long-term survival are better protected
      with higher AZG levels. Female adult cycads have higher AZG levels compared to
      males, suggesting that the benefits of defense could also be linked to
      reproductive costs.

PMID- 27704315
TI  - Lessons from the Far End: Caterpillar FRASS-Induced Defenses in Maize, Rice,
      Cabbage, and Tomato.
AB  - Plant defenses to insect herbivores have been studied in response to several
      insect behaviors on plants such as feeding, crawling, and oviposition. However,
      we have only scratched the surface about how insect feces induce plant defenses.
      In this study, we measured frass-induced plant defenses in maize, rice, cabbage,
      and tomato by chewing herbivores such as European corn borer (ECB), fall armyworm
      (FAW), cabbage looper (CL), and tomato fruit worm (TFW). We observed that
      caterpillar frass induced plant defenses are specific to each host-herbivore
      system, and they may induce herbivore or pathogen defense responses in the host
      plant depending on the composition of the frass deposited on the plant, the plant
      organ where it is deposited, and the species of insect. This study adds another
      layer of complexity in plant-insect interactions where analysis of frass-induced
      defenses has been neglected even in host-herbivore systems where naturally frass
      accumulates in enclosed feeding sites over extended periods of time.

PMID- 27704316
TI  - The Involvment of Hematopoietic-Specific PLC -beta2 in Homing and Engraftment of
      Hematopoietic Stem/Progenitor Cells.
AB  - Migration and bone marrow (BM) homing of hematopoietic stem progenitor cells
      (HSPCs) is regulated by several signaling pathways, and here we provide evidence
      for the involvement in this process of hematopoietic-specific phospholipase C
      beta2 (PLC-beta2). This enzyme is involved in release of intracellular calcium
      and activation of protein kinase C (PKC). Recently we reported that PLC-beta2
      promotes mobilization of HSPCs from BM into peripheral blood (PB), and this
      effect is mediated by the involvement of PLC-beta2 in the release of proteolytic
      enzymes from granulocytes and its role in disintegration of membrane lipid rafts.
      Here we report that, besides the role of PLC-beta2 in the release of HSPCs from
      BM niches, PLC-beta2 regulates the migration of HSPCs in response to chemotactic
      gradients of BM homing factors, including SDF-1, S1P, C1P, and ATP. Specifically,
      HSPCs from PLC-beta2-KO mice show impaired homing and engraftment in vivo after
      transplantation into lethally irradiated mice. This decrease in migration of
      HSPCs can be explained by impaired calcium release in PLC-beta2-KO mice and a
      high baseline level of heme oxygenase 1 (HO-1), an enzyme that negatively
      regulates cell migration.

PMID- 27704317
TI  - The addition of renal sympathetic denervation to pulmonary vein isolation reduces
      recurrence of paroxysmal atrial fibrillation in chronic kidney disease patients.
AB  - BACKGROUND: Atrial fibrillation (AF) frequently complicates chronic kidney
      disease (CKD). AF treatment is challenging and requires complete pulmonary vein
      isolation (PVI). Recently, renal sympathetic denervation (RSD) has been reported
      to reduce AF recurrence when performed alongside PVI. METHODS: A prospective
      therapeutic study of patients with controlled hypertension and paroxysmal AF was
      undertaken. Renal function was evaluated using estimated glomerular filtration
      rate. Outcomes for patients with normal renal function who underwent PVI (n =
      101) were compared with those for CKD patients who underwent either PVI alone (n
      = 96) or PVI + RSD (n = 39). The primary endpoint was recurrence of AF recorded
      by 24-h Holter monitoring. RESULTS: During the 22.4 +/- 12.1 months following
      intervention, the incidence of AF recurrence was higher in CKD patients treated
      with PVI alone (61.5 %) than in CKD patients treated with PVI + RSD (38.5 %; HR
      1.86, 95 % CI 1.14-3.03, P = 0.0251) or patients without CKD subjected to PVI
      (35.6 %; hazard ratio (HR) 2.27, 95 % confidence interval (CI) 1.51-3.42, P <
      0.0001). In particular, the addition of RSD to PVI significantly reduced AF
      recurrence in CKD stage 4, but not stage 2 or 3, patients. Ambulatory blood
      pressure and mean heart rate were not different between groups or time points. No
      complications of either procedure were observed. CONCLUSIONS: PVI + RSD is a safe
      treatment that is superior to PVI alone for treatment of paroxysmal AF in CKD
      patients.

PMID- 27704318
TI  - What Differences in Morphologic Features of the Knee Exist Among Patients of
      Various Races? A Systematic Review.
AB  - BACKGROUND: Most TKA prostheses are designed based on the anatomy of white
      patients. Individual studies have identified key anthropometric differences
      between the knees of the white population and other major ethnic groups, yet
      there is limited understanding of what these findings may indicate if analyzed
      collectively. QUESTION/PURPOSE: What are the differences in morphologic features
      of the distal femur and proximal tibia among and within various ethnicities?
      METHODS: A systematic review of the PubMed database and a hand-search of article
      bibliographies identified 235 potentially eligible English-language studies.
      Studies were excluded if they did not include morphology results or had
      insufficient data for analysis, were unrelated to the distal femur or proximal
      tibia, were conducted in pediatric patients or those undergoing unicondylar knee
      arthroplasty, or bone surface measurements were obtained for trauma products.
      This left 30 eligible studies (9050 knees). Study quality was assessed and
      reported as good, fair, or poor according to the NIH Quality Assessment Tool for
      Observational Cohort and Cross-Sectional Studies. Morphometric data for the
      distal femur and proximal tibia were available for four ethnic groups: East Asian
      (23 studies; 5543 knees), white (11 studies; 3111 knees), Indian (three studies;
      283 knees), and black (three studies; 113 knees). Although relatively
      underrepresented, the knees from the Indian and black studies were maintained for
      hypothesis-generating purposes and to highlight crucial gaps in the data. The two
      key dimensions for selecting a suitable implant based on a patient's unique
      anatomy-AP length and mediolateral (ML) width-were assessed for the femur and
      tibia, in addition to aspect ratio, calculated by dividing the ML width by the AP
      length. Study measurement techniques were compared visually when possible to
      ensure that each pooled study conducted a similar measurement process. Any
      significant measurement outliers were reviewed for eligibility to determine if
      the measurement techniques and landmarks used were comparable to the other
      studies included. RESULTS: White patients had larger femoral AP measurements than
      East Asians (62 mm, [95% CI, 57-66 mm] vs 59 mm, [95% CI, 54-63 mm]; mean
      difference, 3 mm; p < 0.001), a smaller femoral aspect ratio than East Asians
      (1.20, [95% CI, 1.11-1.29] vs 1.25, [95% CI, 1.16-1.34]; mean difference, 0.05; p
      = 0.001), and a larger tibial aspect ratio than black patients (1.55, [95% CI,
      1.40-1.71] vs 1.49, [95% CI, 1.33-1.64]; mean difference, 0.06; p = 0.005).
      CONCLUSIONS: This analysis uncovered differences of size (AP height and ML width
      of the femur and tibia) and shape (tibial and femoral aspect ratios) among knees
      from white, East Asian, and black populations. Future research is needed to
      understand the clinical implications of these discrepancies and to provide
      additional data with underrepresented groups.

PMID- 27704319
TI  - Clinical outcomes of acute kidney injury developing outside the hospital in
      elderly.
AB  - PURPOSE: Although various studies have improved our knowledge about the clinical
      features and outcomes of acute kidney injury developing in the hospital (AKI-DI)
      in elderly subjects, data about acute kidney injury developing outside the
      hospital (AKI-DO) in elderly patients (age >= 65 years) are still extremely
      limited. This study was performed to investigate prevalence, clinical outcomes,
      hospital cost and related factors of AKI-DO in elderly and very elderly patients.
      METHODS: We conducted a prospective, observational study in patients (aged >= 65
      years) who were admitted to our center between May 01, 2012, and May 01, 2013.
      Subjects with AKI-DO were divided into two groups as "elderly" (group 1, 65-75
      years old) and "very elderly" (group 2, >75 years old). Control group (group 3)
      consisted of the hospitalized patients aged 65 years and older with normal serum
      creatinine level. In-hospital outcomes and 6-month outcomes were recorded.
      Rehospitalization rate within 6 months of discharge was noted. Hospital costs and
      mortality rates of each group were investigated. Risk factors for AKI-DO were
      determined. RESULTS: The incidence of AKI-DO that required hospitalization in
      elderly and very elderly patients was 5.8 % (136/2324) and 11 % (100/905),
      respectively (p < 0.001), with an overall incidence of 7.3 % (236/3229). Chronic
      kidney disease (CKD) was developed in 43.4 % of group 1 and 67 % of group 2
      within the 6 months of discharge (p < 0.001). Progression to CKD was
      significantly lower in the control group than in groups 1 and 2 (p < 0.001).
      Mortality rates for groups 1, 2 and 3 were 23.5 % (n = 32), 31 % (n = 31) and 4.2
      % (n = 8), respectively (p < 0.05). Rehospitalization rate within the 6 months of
      discharge for the groups with AKI-DO was higher than for the control group (p <
      0.001). Hospital cost of groups 1 and 2 was significantly higher than that of the
      control group (p < 0.001). Nonsteroidal anti-inflammatory drugs (NSAIDs) (OR:
      6.839, 95 % CI = 4.392-10.648), angiotensin-converting enzyme inhibitors (ACEI)
      (OR: 7.846, 95 % CI = 5.161-11.928), angiotensin receptor blockers (ARB) (OR:
      6.466, 95 % CI = 4.813-8.917), radiocontrast agents (OR: 8.850, 95 % CI = 5.857
      13.372), hypertension (OR: 4.244, 95 % CI = 2.729-6.600), diabetes mellitus (OR:
      2.303, 95 % CI = 1.411-3.761), heart failure (OR: 3.647, 95 % CI = 2.276-5.844)
      and presence of infection (OR: 3.149, 95 % CI = 1.696-5.845) were found as the
      risk factors for AKI-DO in elderly patients (p < 0.001 for all). Patients with
      AKI-DO had higher 6-month mortality rate (HR 1.721, 95 % CI: 1.451-2.043, p <
      0.001). Mortality risk increased 0.519 times at 20th day. CONCLUSIONS: The
      incidence of AKI-DO requiring hospitalization is higher in very elderly patients
      than elderly ones, especially in male gender. Use of ACEI, ARB, NSAID and
      radiocontrast agents is the main risk factors for the development of AKI-DO in
      the elderly.

PMID- 27704320
TI  - Association between serum gamma-glutamyltransferase and chronic kidney disease in
      urban Han Chinese: a prospective cohort study.
AB  - PURPOSE: Limited numbers of literatures have focused on the association between
      gamma-glutamyltransferase (GGT) and chronic kidney disease (CKD), and their
      results were controversial. Therefore, in this study, we set up a large-scale
      cohort of Chinese population to discover and verify the association between serum
      GGT and CKD. METHODS: Our cohort study was based on 21,818 patients who visited
      Health Management Center of Shandong Provincial Hospital, China, to receive
      routine health check-up during the period of 2005-2010, and we used multivariate
      Cox regression model to clarify whether elevated serum GGT increased the risk of
      CKD or not. RESULTS: During the follow-up of 57,891 person-years, 1456 patients
      developed CKD, giving rise to an incidence density of 25.15 per 1000 person-years
      (1456/57,891 person-years). After adjusting gender, age, baseline serum
      creatinine (SCr), body mass index (BMI), serum albumin (ALB), alanine
      aminotransferase (ALT), hemoglobin, white blood cell count (WBC), triglyceride
      (TG), total cholesterol (TC), hypertension, cardiovascular disease (CVD),
      diabetes, smoking and drinking status, the risk for CKD increased with the
      elevated serum GGT quartiles. The hazard ratio (HR) for CKD was 1.326 (95 %
      confidence interval (CI), 1.073-1.639) when the top quartile of serum GGT was
      compared with the bottom one, and the HR of log-transformed serum GGT for CKD was
      1.658 (95 % CI, 1.294-2.125). The results were consistent in males but different
      in females when gender was stratified. CONCLUSION: The result reveals that there
      is a positive relationship between increasing serum GGT levels and the incidence
      of CKD which suggests that elevated GGT level could be a potential indicator for
      risk of CKD.

PMID- 27704321
TI  - Preoperative [99mTc]MIBI SPECT/CT Interpretation Criteria for Localization of
      Parathyroid Adenomas-Correlation with Surgical Findings.
AB  - PURPOSE: Minimally invasive surgery for parathyroid adenomas (PTA) requires
      precise identification and localization of the diseased gland prior to
      exploration for optimal surgical planning. The Perrier classification allows for
      accurate, reproducible, and reliable description of PTA location and
      communication of clinically significant information to surgeons. The current
      study compares the Perrier localization of PTA on
      [99mTc]methoxyisobutylisonitrile ([99mTc]MIBI) single-photon emission computed
      tomography (SPECT)/X-ray computed tomography (CT) with the results of surgery.
      PROCEDURES: Eighty-eight patients (60 females), age 13-82 years, with primary
      hyperparathyroidism underwent [99mTc]MIBI SPECT/CT prior to surgery. Eight
      patients had parathyroid hyperplasia and underwent excision of 3.5 parathyroid
      glands, including five patients with a negative [99mTc]MIBI study and three
      patients with multiple foci of uptake, and were excluded from further analysis.
      Each PTA was localized to Perrier levels A-G. The surgeon located each PTA found
      on surgery using the same classification. PTA localization on SPECT/CT and at
      surgery was compared. RESULTS: Eighty patients with surgically confirmed PTA were
      analyzed. On [99mTc]MIBI SPECT/CT, 63 patients had a single and one patient had
      two PTAs for a total of 65 PTAs. At surgery, 85 PTAs were resected in 80
      patients, including 75 patients with single and 5 with two PTAs. Twenty PTAs
      found on surgery were not detected on [99mTc]MIBI. The relatively lower weight of
      these 20 PTAs is probably the main reason for the false-negative results group.
      The same Perrier localization was determined on SPECT/CT and surgery in 52/65
      PTAs (80 %). In the 13 incongruent cases, the PTAs were localized at different
      locations but on the same side of the thyroid gland. CONCLUSIONS: [99mTc]MIBI
      SPECT/CT accurately localized a PTA according to the Perrier classification in 80
      % of cases. Reporting SPECT/CT results using anatomy-based PTA localization
      criteria accepted by surgeons can contribute significantly towards better
      interspecialty communication and will improve performance of minimally invasive
      surgical removal of PTAs.

PMID- 27704322
TI  - An agent-based simulation model of patient choice of health care providers in
      accountable care organizations.
AB  - Accountable care organizations (ACO) in the United States show promise in
      controlling health care costs while preserving patients' choice of providers.
      Understanding the effects of patient choice is critical in novel payment and
      delivery models like ACO that depend on continuity of care and accountability.
      The financial, utilization, and behavioral implications associated with a
      patient's decision to forego local health care providers for more distant ones to
      access higher quality care remain unknown. To study this question, we used an
      agent-based simulation model of a health care market composed of providers able
      to form ACO serving patients and embedded it in a conditional logit decision
      model to examine patients capable of choosing their care providers. This
      simulation focuses on Medicare beneficiaries and their congestive heart failure
      (CHF) outcomes. We place the patient agents in an ACO delivery system model in
      which provider agents decide if they remain in an ACO and perform a quality
      improving CHF disease management intervention. Illustrative results show that
      allowing patients to choose their providers reduces the yearly payment per CHF
      patient by $320, reduces mortality rates by 0.12 percentage points and
      hospitalization rates by 0.44 percentage points, and marginally increases
      provider participation in ACO. This study demonstrates a model capable of
      quantifying the effects of patient choice in a theoretical ACO system and
      provides a potential tool for policymakers to understand implications of patient
      choice and assess potential policy controls.

PMID- 27704323
TI  - Comparison of emergency department crowding scores: a discrete-event simulation
      approach.
AB  - According to American College of Emergency Physicians, emergency department (ED)
      crowding occurs when the identified need for emergency services exceeds available
      resources for patient care in the ED, hospital, or both. ED crowding is a widely
      reported problem and several crowding scores are proposed to quantify crowding
      using hospital and patient data as inputs for assisting healthcare professionals
      in anticipating imminent crowding problems. Using data from a large academic
      hospital in North Carolina, we evaluate three crowding scores, namely, EDWIN,
      NEDOCS, and READI by assessing strengths and weaknesses of each score,
      particularly their predictive power. We perform these evaluations by first
      building a discrete-event simulation model of the ED, validating the results of
      the simulation model against observations at the ED under consideration, and
      utilizing the model results to investigate each of the three ED crowding scores
      under normal operating conditions and under two simulated outbreak scenarios in
      the ED. We conclude that, for this hospital, both EDWIN and NEDOCS prove to be
      helpful measures of current ED crowdedness, and both scores demonstrate the
      ability to anticipate impending crowdedness. Utilizing both EDWIN and NEDOCS
      scores in combination with the threshold values proposed in this work could
      provide a real-time alert for clinicians to anticipate impending crowding, which
      could lead to better preparation and eventually better patient care outcomes.

PMID- 27704324
TI  - Editorial: Advancements in Pediatric Hepatology - Approach Based Diagnosis and
      Management.

PMID- 27704325
TI  - Intestinal Failure in Children.
AB  - Children with intestinal failure have had improved survival, particularly those
      with extreme short bowel syndrome, over the last 10-15 y. This has been
      attributed to better understanding of the pathophysiology of intestinal failure,
      improvement in line care, recognition of the importance of a team approach as
      well as the progress of intestinal transplant as a viable option. Parenteral
      nutrition remains the cornerstone for the continual survival of these patients.
      This review will cover contemporary approaches to intestinal failure including
      post surgical approaches, non-transplant surgery, dietetic and medication
      approaches during the adaptation process, considerations for home parenteral
      nutrition and latest in intestinal transplantation.

PMID- 27704326
TI  - Predictors of Participation in an eHealth, Family-Based Preventive Intervention
      for Hispanic Youth.
AB  - The Familias Unidas intervention is an efficacious family-based preventive
      intervention for reducing substance use and other health risks among Hispanic
      youth. A current randomized controlled trial (RCT) is examining this
      intervention's efficacy when delivered via the Internet (eHealth). eHealth
      interventions can overcome logistical barriers to participation, yet there is
      limited information about the feasibility of these interventions, especially
      among ethnic minorities. This paper examines participation and predictors of
      participation in the eHealth Familias Unidas intervention in a sample of 113
      Hispanic families whose adolescent had behavioral problems. Analyses examined
      multidimensional ways of characterizing participation, including the following:
      (1) total intervention participation, (2) initial engagement (participating in at
      least one of the first three intervention sessions), (3) completing the pre
      recorded, eHealth parent group sessions, and (4) participating in the live,
      facilitator-led, eHealth family sessions. Participation in this eHealth
      intervention was comparable to, and in most cases higher than, previous, face-to
      face Familias Unidas interventions. High levels of baseline family stress were
      associated with lower initial engagement and lower family session participation.
      Greater parental Hispanicism was associated with more participation in eHealth
      parent group sessions and across the total intervention. Higher levels of
      baseline effective parenting, in other words less intervention need, were
      significantly associated with lower levels of total intervention participation
      and lower levels of family session participation. Implications for preventive
      interventions delivered via Internet are discussed.

PMID- 27704327
TI  - Obstructive sleep apnea (OSA) and clinical depression-prevalence in a sleep
      center.
AB  - BACKGROUND: This study aimed to determine the prevalence of clinical depression
      as defined by ICD-10 criteria in all patients with obstructive sleep apnea (OSA)
      referred to a sleep center. METHODS: Prospective general and sleep evaluations
      were conducted in 447 consecutive patients referred to our sleep center during
      the first quarter of 2008. Inclusion criteria were Apnea Hypopnea Index (AHI) >
      9, completion of the Beck Depression Inventory (BDI-II) with a score >=14 and
      World Health Organization WHO-5 Well-Being Index (WHO-5) <= 13. The subsequent
      psychiatric examination according to ICD-10 criteria was performed by in-house
      clinical sleep specialists. RESULTS: A total of 447 patients were surveyed, of
      whom 322 had an AHI > 9. Out of these, 85 met the combined screening criterion
      BDI II >= 14 and WHO-5 <= 13. Eighty-one patients underwent a psychiatric
      examination by psychiatric sleep specialists. In 21.5 % of the sample, clinical
      depression was diagnosed. Other complaints existed in 12 % (n = 10); 7 % (n = 6)
      of patients had a different psychiatric diagnosis. CONCLUSIONS: The prevalence of
      clinical depression according to ICD-10 criteria in a selected clinical sample
      (referred to the sleep center) was 21.5 %. Mood scales tend to overestimate
      complaints as compared to psychiatric consultation. Interdisciplinary cooperation
      is recommended for both OSA patients with symptoms of depression and depressed
      patients with treatment resistance.

PMID- 27704328
TI  - Impact of gender and sleep position on relationships between anthropometric
      parameters and obstructive sleep apnea syndrome.
AB  - OBJECTIVE: Considering the mechanisms by which obesity affects obstructive sleep
      apnea syndrome (OSAS) and the differences of fat distribution depending on
      gender, associations between anthropometric parameters, and OSAS may differ
      depending on gender or sleep position. We analyzed the impact of gender and sleep
      position on the relationship between fat distribution and development of OSAS.
      METHODS: One thousand thirty-two consecutive subjects were analyzed. Recorded
      anthropometric measurements and overnight polysomnographic data of the subjects
      were reviewed retrospectively. The presence of OSAS was defined by the
      respiratory disturbance index (RDI) >=5 with documented symptoms of excessive
      daytime sleepiness. RESULTS: Eight hundred fifty-eight males and 174 females were
      included. Male subjects had significantly higher body mass index (BMI), larger
      waist circumference (WC), and lower percent of overall body fat (P < 0.0001, P <
      0.0001, and P < 0.0001, respectively). The severity of OSAS was significantly
      higher in male subjects (RDI 26.9 +/- 22.4 in males vs. 10.2 +/- 13.8 in females,
      P < 0.0001). In male subjects, BMI, WC, and overall body fat were significantly
      associated with severity of OSAS and had larger impacts on supine RDI than
      lateral RDI. Overall body fat was not associated with severity of OSAS in female
      subjects, and there were no significant differences of the associations between
      all anthropometric parameters and RDIs depending on sleep position. CONCLUSIONS:
      Evaluation of the correlation of anthropometric data with severity of OSAS should
      consider sleep position as well as gender.

PMID- 27704329
TI  - Impact of Population Recruitment on the HIV Epidemics and the Effectiveness of
      HIV Prevention Interventions.
AB  - Mechanistic mathematical models are increasingly used to evaluate the
      effectiveness of different interventions for HIV prevention and to inform public
      health decisions. By focusing exclusively on the impact of the interventions, the
      importance of the demographic processes in these studies is often underestimated.
      In this paper, we use simple deterministic models to assess the effectiveness of
      pre-exposure prophylaxis in reducing the HIV transmission and to explore the
      influence of the recruitment mechanisms on the epidemic and effectiveness
      projections. We employ three commonly used formulas that correspond to constant,
      proportional and logistic recruitment and compare the dynamical properties of the
      resulting models. Our analysis exposes substantial differences in the transient
      and asymptotic behavior of the models which result in 47 % variation in
      population size and more than 6 percentage points variation in HIV prevalence
      over 40 years between models using different recruitment mechanisms. We outline
      the strong influence of recruitment assumptions on the impact of HIV prevention
      interventions and conclude that detailed demographic data should be used to
      inform the integration of recruitment processes in the models before HIV
      prevention is considered.

PMID- 27704330
TI  - Day-to-Day Population Movement and the Management of Dengue Epidemics.
AB  - Dengue is a growing public health problem in tropical and subtropical cities. It
      is transmitted by mosquitoes, and the main strategy for epidemic prevention and
      control is insecticide fumigation. Effective management is, however, proving
      elusive. People's day-to-day movement about the city is believed to be an
      important factor in the epidemiological dynamics. We use a simple model to
      examine the fundamental roles of broad demographic and spatial structures in
      epidemic initiation, growth and control. We show that the key factors are local
      dilution, characterised by the vector-host ratio, and spatial connectivity,
      characterised by the extent of habitually variable movement patterns. Epidemic
      risk in the population is driven by the demographic groups that frequent the
      areas with the highest vector-host ratio, even if they only spend some of their
      time there. Synchronisation of epidemic trajectories in different demographic
      groups is governed by the vector-host ratios to which they are exposed and the
      strength of connectivity. Strategies for epidemic prevention and management may
      be made more effective if they take into account the fluctuating landscape of
      transmission intensity associated with spatial heterogeneity in the vector-host
      ratio and people's day-to-day movement patterns.

PMID- 27704332
TI  - A cost-utility analysis of dabigatran, enoxaparin, and usual care for venous
      thromboprophylaxis after hip or knee replacement surgery in Thailand.
AB  - To analyze the cost-utility of oral dabigatran etexilate, enoxaparin sodium
      injection, and no intervention for venous thromboembolism (VTE) prophylaxis after
      total hip or knee replacement (THR/TKR) surgery among Thai patients. A cost
      utility analysis using a decision tree model was conducted using societal and
      healthcare payers' perspectives to simulate relevant costs and health outcomes
      covering a 3-month time horizon. Costs were adjusted to year 2014. The
      willingness-to-pay threshold of THB 160,000 (USD 4926) was used. One-way
      sensitivity and probabilistic sensitivity analyses using a Monte Carlo simulation
      were performed. Compared with no VTE prophylaxis, dabigatran and enoxaparin after
      THR and TKR surgery incurred higher costs and increased quality adjusted life
      years (QALYs). However, their incremental cost-effectiveness ratios were high
      above the willingness to pay. Compared with enoxaparin, dabigatran for THR/TKR
      lowered VTE complications but increased bleeding cases; dabigatran was cost
      saving by reducing the costs [by THB 3809.96 (USD 117.30) for THR] and producing
      more QALYs gained (by 0.00013 for THR). Dabigatran (vs. enoxaparin) had a 98 %
      likelihood of being cost effective. Dabigatran is cost-saving compared to
      enoxaparin for VTE prophylaxis after THR or TKR under the Thai context. However,
      both medications are not cost-effective compared to no thromboprophylaxis.

PMID- 27704331
TI  - Admixing of MPTP-Resistant and Susceptible Mice Strains Augments Nigrostriatal
      Neuronal Correlates to Resist MPTP-Induced Neurodegeneration.
AB  - Disease genetics in admixed populations like Hispanic-Americans, African
      Americans, etc. are gaining importance due to high disease burden in them.
      Furthermore, epidemiological studies conclusively prove ethnicity-based
      differential prevalence of Parkinson's disease (PD), since the American
      Caucasians are more susceptible than Asian-Indians and Africans. Contradictorily,
      Anglo-Indians, an admixture of Europeans and Asian-Indians are five-times less
      susceptible than Indians. We evaluated the neural basis of this phenomenon using
      the cytomorphological features of susceptibility to nigrostriatal neurotoxin 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The nigral dopaminergic
      neuronal numbers, their size and tyrosine hydroxylase (TH), PitX3 and Nurr1
      expression were compared in MPTP-susceptible C57BL/6J mice, MPTP-resistant CD-1
      mice and their crossbreds using stereology, morphometry and densitometry.
      Apoptotic index was evaluated by TUNEL-assay and caspase-3 expression. Striatal
      volume, TH and glial derived neurotrophic factor (GDNF) expression were studied.
      The normal CD-1 and crossbreds had significantly more, although smaller, nigral
      dopaminergic neurons than C57BL/6J, and a larger striatum. The crossbreds had
      higher TH, Nurr1 and PitX3 levels. MPTP administration caused loss of ~50-60 %
      nigral dopaminergic neurons in C57BL/6J and ~15 % in CD-1, but none in
      crossbreds. MPTP-induced cellular shrinkage in C57BL/6J was contrasted by nuclear
      enlargement without somal alterations in resistant strains. MPTP lowered the
      striatal TH and GDNF in C57BL/6J. Elevated striatal GDNF in CD-1 and crossbreds
      could be of compensatory nature and complemented the reduced nigral caspase-3
      expression to attenuate and/or block apoptosis. Similar neural correlates of
      resilience are envisaged in the Anglo-Indian population. Thus, we present the
      core neuroanatomical features of resilience against PD and evidence for ethnicity
      based differential prevalence.

PMID- 27704333
TI  - Risk of intracranial hemorrhage associated with therapeutic anticoagulation for
      venous thromboembolism in cancer patients: a systematic review and meta-analysis.
AB  - Intracranial hemorrhage (ICH) in cancer patients can result from tumor bleeding
      and from antitumor and anticoagulation therapy. The effect of anticoagulation on
      the incidence of ICH in cancer patients has not been quantified. Our objective
      was to determine the risk of intracranial hemorrhage associated with
      anticoagulation therapy for cancer-associated venous thromboembolism (VTE).
      Systematic review and meta-analysis of studies assessing the safety of
      anticoagulation therapy in patients with cancer-associated VTE. The primary
      endpoint of interest was the incidence of ICH and secondary outcomes included all
      major bleeding, and the time to ICH and major bleeding. After identifying 595
      studies, five studies and 2089 patients were included in the analyses. We found
      that the relative risk (RR) for ICH was 0.494, 95 % CI (0.105-2.331) when low
      molecular weight heparin (LMWH) with vitamin K antagonist (VKA) anticoagulants
      were compared. No statistically significant differences in risk were measured.
      The risk of major bleeding using any type of anticoagulation therapy in patients
      with cancer-associated VTE was RR 0.853, 95 % CI (0.549, 1.327). After meta
      analytic review of data published through August 2015, we conclude that
      therapeutic anticoagulation with LMWH given <=6 months does not increase the risk
      of ICH in cancer patients compared to VKA. The risk of ICH in cancer patients is
      also similar to that of non-cancer patients. Available data were insufficient to
      determine if the ICH risk increase changes when the duration of anticoagulation
      is >6 months.

PMID- 27704334
TI  - Diacylglycerol acyltransferase 1 (DGAT1) inhibition by furofuran lignans from
      stems of Acanthopanax senticosus.
AB  - Two new furofuran lignans were isolated from the stems of Acanthopanax
      senticosus, along with seven known compounds. Their structures were all
      determined by spectroscopic analyses and chemical methods. All the isolates were
      evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Compounds 1
      and 2 were found to exhibit selective inhibitory activity on DGAT1 with IC50
      values 89.5 +/- 1.5 and 57.5 +/- 1.3 uM, respectively.

PMID- 27704335
TI  - Aristoyunnolin H attenuates extracellular matrix secretion in cardiac fibroblasts
      by inhibiting calcium influx.
AB  - Aristoyunnolin H is a novel aristophyllene sesquiterpenoid isolated from the
      traditional Chinese medicine Aristolochia yunnanensis Franch. The present
      research was designed to explore the anti-fibrotic effects of aristoyunnolin H in
      adult rat cardiac fibroblasts (CFs) stimulated with angiotensin II (Ang II).
      Western blot analysis data showed that aristoyunnolin H reduced the upregulation
      of fibronectin (FN), connective tissue growth factor and collagen I(Col I)
      production induced by Ang II in CFs. By studying the dynamic intracellular
      changes of Ca2+, we further found that while aristoyunnolin H relieved the
      calcium influx, it has no effect on intracellular calcium store release.
      Meanwhile, aristoyunnolin H also inhibited the Ang II-stimulated phosphorylation
      of Ca2+/calmodulin-dependent protein kinase II. In conclusion, aristoyunnolin H
      may attenuate extracellular matrix secretion in vitro by inhibiting Ang II
      induced calcium signaling.

PMID- 27704336
TI  - Cytotoxicity of lipid-soluble ginseng extracts is attenuated by plasma membrane
      redox enzyme NQO1 through maintaining redox homeostasis and delaying apoptosis in
      human neuroblastoma cells.
AB  - Lipid-soluble ginseng extracts (LSGE) is known to inhibit many types of cancer
      cells through arresting cell cycle and inducing apoptosis. Usually, normal cells
      are can also be damaged by anti-tumor reagents. The plasma membrane redox system
      (PMRS) is enhanced to compensate mitochondrial dysfunction and impaired energy
      metabolism. NADH-quinone oxidoreductase 1 (NQO1), a plasma membrane redox enzyme,
      is known to be induced by panaxytriol, one of components of lipid-soluble ginseng
      extracts (LSGE). The objective of this study was determine the mechanisms of NQO1
      involved in neuroprotection in response to cytotoxicity induced by LSGE. Exposure
      of control SH-SY5Y cells to LSGE resulted in dramatic loss of cell viability in a
      dose-dependent manner. The loss of cell viability was significantly recovered in
      cells transfected with NQO1. LSGE-induced cell death occurred through apoptosis
      such as cell shrinkage, chromatin condensation and cleavage of poly (ADP-ribose)
      polymerase. These apoptotic features were significantly attenuated by
      overexpression of NQO1. Levels of oxidative/nitrative damage were highly elevated
      by LSGE in a dose-dependent manner. However, these elevated levels were greatly
      reduced by overexpression of NQO1. In addition, overexpression of NQO1 attenuated
      the decrease in mitochondrial complex I activity caused by LSGE. Taken together,
      these findings suggest that overexpressed NQO1 can protect cells against LSGE
      induced cytotoxicity through lowering oxidative/nitrative damage and delaying
      apoptosis, supporting that stimulation of NQO1 activity could be a therapeutic
      targets in neurodegeration.

PMID- 27704337
TI  - Modeling the differentiation of A- and C-type baroreceptor firing patterns.
AB  - The baroreceptor neurons serve as the primary transducers of blood pressure for
      the autonomic nervous system and are thus critical in enabling the body to
      respond effectively to changes in blood pressure. These neurons can be separated
      into two types (A and C) based on the myelination of their axons and their
      distinct firing patterns elicited in response to specific pressure stimuli. This
      study has developed a comprehensive model of the afferent baroreceptor discharge
      built on physiological knowledge of arterial wall mechanics, firing rate
      responses to controlled pressure stimuli, and ion channel dynamics within the
      baroreceptor neurons. With this model, we were able to predict firing rates
      observed in previously published experiments in both A- and C-type neurons. These
      results were obtained by adjusting model parameters determining the maximal ion
      channel conductances. The observed variation in the model parameters are
      hypothesized to correspond to physiological differences between A- and C-type
      neurons. In agreement with published experimental observations, our simulations
      suggest that a twofold lower potassium conductance in C-type neurons is
      responsible for the observed sustained basal firing, where as a tenfold higher
      mechanosensitive conductance is responsible for the greater firing rate observed
      in A-type neurons. A better understanding of the difference between the two
      neuron types can potentially be used to gain more insight about pathophysiology
      and treatment of diseases related to baroreflex function, e.g. in patients with
      autonomic failure, a syndrome that is difficult to diagnose in terms of its
      pathophysiology.

PMID- 27704338
TI  - Staple Line Bleeding in Sleeve Gastrectomy: a Simple and Cost-Effective Solution.

PMID- 27704339
TI  - Conversion of Vertical Sleeve Gastrectomy to a Functional Single-Anastomosis
      Gastric Bypass: Technique and Preliminary Results Using a Non-Adjustable Ring
      Instead of Stapled Division.
AB  - BACKGROUND: Recent data show that some patients will have insufficient weight
      loss or experience weight regain after sleeve gastrectomy. Dilation of the sleeve
      over time or use of an inadequate technique may contribute to relapse of morbid
      obesity. Repeat sleeve gastrectomy is the most obvious option but requires
      stapling of scarred tissue, has a higher risk of leakage, and is prone to re
      enlargement with time. We herein describe a simple and innovative technique with
      which to revise vertical sleeve gastrectomy (VSG) into functional single
      anastomosis gastric bypass (f-SAGB). MATERIALS AND METHODS: Twelve VSGs were
      converted to f-SAGB by placing a GaBP Ring (Bariatec Corp., Palos Verdes
      Peninsula, CA, USA) at the base of the "sleeve" and performing the anastomosis
      above the ring. The length of the biliopancreatic loop was chosen according to
      the volume of the pouch and the patient's residual eating capability. RESULTS:
      All procedures were completed by laparoscopy and were uneventful. The average
      decrease in the body mass index was from 41.0 to 29.5 kg/m2 at the 12-month
      follow-up. No ring-related complications were reported. CONCLUSION: f-SAGB is a
      low-risk and effective option with which to revise VSG in patients with
      inadequate weight loss. Avoiding detachment of the pouch from the antrum assures
      full reversibility of the procedure and preserves the chance to explore the
      remnant stomach and biliary tree.

PMID- 27704340
TI  - Evaluation of individual cognitive remediation therapy (CRT) for the treatment of
      young people with anorexia nervosa.
AB  - PURPOSE: Research suggests that there are cognitive inefficiencies underlying
      Anorexia Nervosa (AN), with CRT showing promise in improving these inefficiencies
      in adults. This area has yet to be explored in a younger population. The aim of
      this study was to evaluate the use of CRT for young people. METHODS: A within
      subjects design was used to compare the performance of children and adolescents
      with AN on several neuropsychological measures administered before and after a
      course of CRT. RESULTS: Ninety-two female participants diagnosed with AN aged
      between 11 and 17 (M = 14.8, SD = 1.6), all receiving treatment at a specialist
      inpatient unit. The assessment consisted of the Rey-Osterrieth Complex Figure
      test (ROCFT), the Behaviour Rating Inventory of Executive Function-Self-Report
      (BRIEF-SR), and the D-KEFS Colour-Word Interference Test (CWT). Repeated-measures
      t tests were used to analyse the ROCFT and BRIEF-SR data. There was a significant
      improvement in Central Coherence Index (p < .001), Immediate Recall (p < .001),
      Shift (p < .001) Cognitive Shift (p = 002), Behavioural shift (p < .001),
      Emotional Control (p < .001), Working Memory (p = .001), Plan/Organize (p <
      .001), Monitor (p = .001) BRI (p < .001), MI (p = .001), and GEC (p < .001). On
      the D-KEFS CWT, a repeated-measure Wilcoxon signed-rank test revealed a
      significant improvement in Error Rate (p = .019) and a repeated-measures t test
      revealed a significant improvement in time taken (p < .001). CONCLUSIONS: Results
      suggest that CRT for children and adolescents with AN could strengthen specific
      cognitive domains.

PMID- 27704341
TI  - Shame proneness and eating disorders: a comparison between clinical and non
      clinical samples.
AB  - PURPOSE: To explore the relationship between shame proneness, eating disorders
      outcomes and psychological aspects of patients with eating disorders (ED).
      METHODS: Sixty-six girls applying for inpatient treatment for ED and 110 female
      undergraduate students were assessed using the Eating Disorder Inventory-3 and
      the Shame Proneness Scale of the Test of Self-Conscious Affect. RESULTS: Shame
      proneness showed significant correlations with several ED components and
      psychological scales of EDI-3, with some variations across the subgroups. Shame
      proneness levels were significantly higher in the clinical group than in
      controls. CONCLUSIONS: Shame proneness can be an important component for the
      development and the maintenance of ED due to a strong correlation not only with
      ED symptoms but also with psychological aspects of this disease, in both clinical
      and non-clinical samples.

PMID- 27704344
TI  - Morphofunctional Characteristics of Human Lymphocytes after In Vitro Activation.
AB  - We describe a method of activation of lymphocytes isolated from the peripheral
      blood of patients with cutaneous melanoma and cultured in serum-free medium in
      the presence of IL-2 and IL-15. Viability, proliferative, cytotoxic, and
      functional activities of lymphocytes are evaluated. The lymphocytes actively
      proliferated in this nutrient medium and can be activated in vitro. The method
      for obtaining sufficient amount of activated lymphocytes can be recommended for
      adoptive cell immunotherapy of cancer patients.

PMID- 27704342
TI  - Sustaining Work Participation Across the Life Course.
AB  - Introduction Many disability prevention strategies are focused on acute injuries
      and brief illness episodes, but there will be growing challenges for employers to
      manage circumstances of recurrent, chronic, or fluctuating symptoms in an aging
      workforce. The goal of this article is to summarize existing peer-review research
      in this area, compare this with employer discourse in the grey literature, and
      recommend future research priorities. Methods The authors participated in a year
      long sponsored collaboration that ultimately led to an invited 3-day conference,
      "Improving Research of Employer Practices to Prevent Disability", held October 14
      16, 2015, in Hopkinton, Massachusetts, USA. The collaboration included a topical
      review of the scientific and industry literature, group discussion to identify
      key areas and challenges, drafting of initial documents, and feedback from peer
      researchers and a special panel of experts with employer experience. Results
      Cancer and mental illness were chosen as examples of chronic or recurring
      conditions that might challenge conventional workplace return-to-work practices.
      Workplace problems identified in the literature included fatigue, emotional
      exhaustion, poor supervisor and co-worker support, stigma, discrimination, and
      difficulties finding appropriate accommodations. Workplace intervention research
      is generally lacking, but there is preliminary support for improving workplace
      self-management strategies, collaborative problem-solving, and providing
      checklists and other tools for job accommodation, ideas echoed in the literature
      directed toward employers. Research might be improved by following workers from
      an earlier stage of developing workplace concerns. Conclusions Future research of
      work disability should focus on earlier identification of at-risk workers with
      chronic conditions, the use of more innovative and flexible accommodation
      strategies matched to specific functional losses, stronger integration of the
      workplace into on-going rehabilitation efforts, and a better understanding of
      stigma and other social factors at work.

PMID- 27704343
TI  - New Business Structures Creating Organizational Opportunities and Challenges for
      Work Disability Prevention.
AB  - Purpose Flexible work arrangements are growing in order to develop resource
      efficient production and because of advanced technologies, new societal values,
      changing demographics, and globalization. The article aims to illustrate the
      emerging challenges and opportunities for work disability prevention efforts
      among workers in alternate work arrangements. Methods The authors participated in
      a year-long collaboration that ultimately led to an invited 3-day conference,
      "Improving Research of Employer Practices to Prevent Disability," held October 14
      16, 2015, in Hopkinton, Massachusetts, USA. The collaboration included a topical
      review of the literature, group conference calls to identify key areas and
      challenges, drafting of initial documents, review of industry publications, and a
      conference presentation that included feedback from peer researchers and a
      roundtable discussion with experts having direct employer experience. Results
      Both worker and employer perspectives were considered, and four common alternate
      work arrangements were identified: (a) temporary and contingent employment; (b)
      small workplaces; (c) virtual work/telework; and (d) lone workers. There was
      sparse available research of return-to-work (RTW) and workplace disability
      management strategies with regard to alternate work patterns. Limited research
      findings and a review of the grey literature suggested that regulations and
      guidelines concerning disabled workers are often ambiguous, leading to
      unsatisfactory protection. At the workplace level, there was a lack of research
      evidence on how flexible work arrangements could be handled or leveraged to
      support RTW and prevent disability. Potential negative consequences of this lack
      of organizational guidance and information are higher costs for employers and
      insurers and feelings of job insecurity, lack of social support and integration,
      or work intensification for disabled workers. Conclusions Future studies of RTW
      and workplace disability prevention strategies should be designed to reflect the
      multiple work patterns that currently exist across many working populations, and
      in particular, flexible work arrangements should be explored in more detail as a
      possible mechanism for preventing disability. Labor laws and policies need to be
      developed to fit flexible work arrangements.

PMID- 27704345
TI  - Methodological Approaches to In Vitro Evaluation of Transcription Activity of
      Nuclear Factor Kappa B (NF-kappaB) in Sensory Neurons.
AB  - Transcription activity of NF-kappaB in sensory neurons was analyzed in vitro
      using classical immunocytochemical methods and transgenic technologies.
      Activation of NF-kappaB in NIH3T3 cells and in murine sensory neurons after in
      vitro stimulation with TNF-alpha was demonstrated by the immunocytochemical
      method; however, the expression of the reporter NF-kappaB/LacZ transgene was
      detected only after addition of histon deacetylase inhibitor. Hence, formally
      contradictory conclusions from the results of immunocytochemical analysis and
      reporter transgene expression were in line with the hypothesis on epigenetic
      repression of NF-kappaB activity in sensory neurons mediated by histon
      deacetylases.

PMID- 27704346
TI  - Morphological Studies of Hepatocellular Carcinomas in Male CBA Mice with High
      Liability to Cancer under the Effect of Phytoadaptogen.
AB  - Treatment of CBA mice predisposed to cancer with a complex phytoadaptogen in the
      therapeutic and preventive modes led to the appearance of moderate and low
      differentiation hepato-cellular carcinomas infiltrated by leukocytes. Destructive
      signs were detected in tumor tissue.

PMID- 27704347
TI  - Sources of Reactive Oxygen and Nitrogen Species in Tissue Microenvironment of
      Hernioplasty Materials.
AB  - Titanium and polypropylene mesh endoprostheses were implanted into the rat
      abdominal cavity and the populations of cells migrating to their surface were
      analyzed. On both materials, the cells were presented mainly by macrophages that
      proliferated, activated, and fused to form multinuclear cells. Contact with the
      foreign surface triggered superoxide anion generation and myeloperoxidase
      synthesis by macrophages (these processes were more intense on polypropylene
      implants than on titanium ones) and stimulated production of nitric oxide by
      macrophage. It was hypothesized that the effects of free nitrogen and oxygen
      radicals lead to oxidation and destruction of the polypropylene endoprosthesis
      surface.

PMID- 27704348
TI  - Effect of Hyperlipidemia and Plasma Cytokine Levels in Rats after Anterior
      Abdominal Wall Reconstruction with the Use of Synthetic Endoprostheses.
AB  - The effect of hyperlipidemia on the systemic production of cytokines was
      evaluated in the plasma of rats after anterior abdominal wall reconstruction with
      polypropylene (Esfil) and polytetrafluorethylene (Ecoflon) endoprostheses. The
      reference group was formed from animals without hyperlipidemia, in which anterior
      abdominal wall plasty was carried out with the use of the same endoprostheses.
      Intact rats without hyperlipidemia and intervention served as the control.
      Hypercytokinemia was detected on days 1-10 after reconstructive surgery on the
      anterior abdominal wall. Polytetrafluoroethylene alloplasty was associated with
      higher plasma production of pro- and anti-inflammatory cytokines, which
      characterized mainly the implant reactogenicity. Hyperlipidemia modified the
      reactivity of immunocompetent cells to the endoprosthesis. A progressive decrease
      in the content of proinflammatory cytokines (IL-1beta and TNF-alpha) was observed
      by day 10 after endoprosthesis implantation, this decrease being more manifest in
      response to polytetrafluoroethylene. High plasma levels of pro- and
      antiinflammatory cytokines (IL-1beta, INF-alpha, IFN-gamma, and IL-10) were
      detected in hyperlipidemic rats on day 1 after polypropylene plasty; by day 10,
      the plasma level of IFN-gamma increased, which reflected positive activation of
      Th1 lymphocytes.

PMID- 27704349
TI  - Effect of Preliminary Injection of Bone Marrow Cell Total RNA on Erythropoiesis
      Recovery Dynamics in Rats Exposed to an Acute gamma-Irradiation.
AB  - Total RNA from the bone marrow of healthy donor rats was injected to experimental
      rats 6 h, 2 h, or 30 min prior to a single gamma-irradiation in the sublethal
      dose of 6 Gy. Injection total RNA 30 min prior to the exposure most effectively
      restored erythropoiesis in experimental animals. In 5 days, reticulocyte count in
      these animals 30-fold surpassed the control (injection of 0.9% NaCl). In 12 days,
      the content of new erythroblastic islands in the bone marrow in rats injected
      with the total RNA 2 h or 30 min prior to irradiation increased significantly and
      erythropoiesis recovery activation was observed.

PMID- 27704350
TI  - Magnetic Resonance Imaging of Brain Involvement in Dogs Using Paramagnetic
      Contrast Enhancement with Mn(II)-DCTA P.
AB  - Experimental study of a new paramagnetic complex Mn-DCTA is carried out. The
      complex (0.5 M manganese(II) solution with trans-1,2-diamine cyclohexane
      N,N,N',N'-tetraacetic acid; Cyclomang) was used for contrast magnetic resonance
      imaging visualization of CNS involvement in dogs with severe forms of Babesia
      canis infection. CNS injuries were visualized in all cases, with highly intense
      contrasting at the expense of Mn-DCTA accumulation at the periphery of the
      damaged zone. Quantitative evaluation of the paramagnetic accumulation in the
      focus showed that the amplification index wa s 1.19+/-0.11 for the central areas
      and 1.47+/-0.17 for the peripheral ones. The pituitary (1.18+/-0.05) and vascular
      plexuses of the lateral ventricles (1.12+/-0.09) were also contrasted. Injection
      of the paramagnetic to dogs was not associated with any kinds of pathological or
      physiological reactions. Mn-DCTA complex allowed contrast visualization of the
      focal injuries to the CNS and could be regarded as a paramagnetic contrast agent
      for magnetic resonance imaging of brain injuries in dogs.

PMID- 27704351
TI  - Polymorphic Variants rs13155212 (T/C) and rs7704267 (G/C) in the AGGF1 Gene and
      Risk of Varicose Veins of the Lower Extremities in the Population of Ethnic
      Russians.
AB  - We analyzed associations between single nucleotide polymorphisms (SNP) rs13155212
      and rs7704267 in the AGGF1 gene (angiogenic factor with G patch and FHA domains
      1) and the risk of risk of varicose veins of the legs in ethnic Russians.
      Frequencies of alleles, genotypes, and haplotypes were estimated in the sample of
      patients with this disease (474 patients) and in the control group of
      participants (478 volunteers) without a history of chronic venous disease. None
      of the studied polymorphisms was associated with the risk of this pathology. The
      whole AGGF1 gene sequence lies in a single block of high linkage disequilibrium,
      and both studied polymorphic variants are representative of all other SNP within
      this region. From these results, a conclusion was made that AGGF1 gene
      polymorphism does not affect the risk of varicose veins of the legs in ethnic
      Russians, or its contribution is low and can be revealed only after analysis of
      larger cohorts.

PMID- 27704352
TI  - Nanohybride Materials Based on Magnetite-Gold Nanoparticles for Diagnostics of
      Prostate Cancer: Synthesis and In Vitro Testing.
AB  - We synthesized a fluorescence conjugate and modified magnetite-gold nanoparticles
      carrying prostate specific membrane antigen (PSMA) as the ligand. Analysis of
      their binding to human prostate cancer cell lines PC-3 (PSMA-) and LNCaP (PSMA+)
      showed selective interaction of the synthesized conjugate and modified
      nanoparticles with LNCaP cells. These findings suggest that these nanoparticles
      can be used in tissue-specific magnetic-resonance imaging.

PMID- 27704353
TI  - Effect of Potassium Comenate on CNS Functional Status in Rodents Exposed to
      Combined Hypoxia and Hypercapnia in Comparison with Normally Ventilated Animals.
AB  - The effects of potassium comenate on functional state of CNS in mice and rats
      were studied in the open-field and hole-board tests under control conditions and
      after acute exposure to hypoxia-hypercapnia. The effects of potassium comenate on
      CNS were also studied in rodents subjected to propofol-induced sleep. Preliminary
      administration of 4 mg/kg potassium comenate for 3 days attenuated the
      posthypoxic changes in behavioral reactions (emotional anxiety/reactivity). The
      pronounced stress-protective effect of potassium comenate was observed both on
      days 1 and 14 after exposure to hypoxia-hypercapnia. Under normal conditions,
      potassium comenate moderated behavioral reactions and augmented somniferous
      effect of propofol. We hypothesized that the antihypoxic effect of potassium
      comenate is determined by its stress-protective and sedative potencies.

PMID- 27704354
TI  - Differential Diagnostics of Neoplastic and Inflammatory Processes in the Brain by
      Modifications NMDA Receptor Activity in Blood Cells with Verapamil and Ketamine.
AB  - For the development of methods of additional differential diagnostics of gliomas
      of various grades of malignancy and gliomas and local inflammatory processes in
      the CNS we studied the intensity of aggregation of peripheral blood cells under
      the influence of channel blockers ketamine and verapamil. In in vitro
      experiments, verapamil and ketamine in various dilutions (from 10 to 100,000
      times) were added to blood samples and the effects of these dilutions on the
      intensity of blood aggregation in patients with gliomas of different degree of
      malignancy, traumatic brain injuries, and other types of neurosurgical
      pathologies were studied. A correlation was revealed between the decrease in
      surface charge of blood cells and the type of neurosurgical pathology. The use of
      functional properties of potential-dependent inotropic NMDA receptors and calcium
      channels allowed indirect estimation of their activity via parameters of blood
      cell aggregation induced by channel blockers ketamine and verapamil.

PMID- 27704355
TI  - Serum Heat Shock Protein 70, as a Potential Biomarker for Small Cell Lung Cancer.
AB  - The 70 kDa heat shock protein (Hsp70) is a highly conservative molecular
      chaperone, that has important role in cell integrity. Recently considerable
      amount of data are accumulating on the potential role of Hsp70 in carcinogenesis
      and tumor progression. Most papers are focusing on intracellular or membrane
      bound protein, however very limited data exist on serum Hsp70, that can also
      induce innate and adaptive immune response. Previously we have published data on
      the correlation between coloretal cancer progression and serum Hsp70
      concentration. The objective of this study was to compare the serum Hsp70 level
      in patients with small cell lung cancer (SCLC n = 70) and age matched healthy
      controlls (n = 121) and correlate Hsp70 level with other known serum biomarkers
      (LDH and NSE) of the disease. We found that the serum level of Hsp70 was
      significantly higher in SCLC patients compared to control subjects (mean value
      6.91 vs 2.47 ng/ml, p = 0.001). The highest Hsp70 concentration was measured in
      stage IV advanced SCLC (Stage IV versus Stage I-III disease: 9.91 vs 4.38 ng/ml,
      p = 0.003). The serum Hsp70 level correlated with serum LDH (r = 0.426, p <
      0,001) and NSE level (r = 0.455, p < 0,001). We found that high serum Hsp70 level
      predicted unfavorable survival, risk of death within 1 year was more than 3 times
      higher in patients with high baseline Hsp70 level (HR:3.509, CI: 1.066-11.562; p
      = 0.039). Our observations indicate that serum Hsp70 could be a valuable
      diagnostic and prognostic marker in small cell lung cancer.

PMID- 27704356
TI  - MicroRNA-27b exerts an oncogenic function by targeting Fbxw7 in human
      hepatocellular carcinoma.
AB  - Aberrant expression of microRNAs (miRNAs) plays fundamental effect on the
      pathogenesis of hepatocellular carcinoma (HCC). MiR-27b was previously found to
      play important roles in human cancers. However, its expression status, clinical
      significance, and biological functions in HCC remain largely unclear. The
      expression status of miR-27b in HCC specimens and cells were determined with qRT
      PCR. MTT, 5-bromodeoxyuridine (BrdU) proliferation assays, and flow cytometry
      analysis were carried out to assay proliferation, cell cycle, and apoptosis. A
      subcutaneous model was used to evaluated the HCC tumor growth in vivo. The
      putative target gene of miR-27b was disclosed by TargetScan and a luciferase
      reporter assay. The levels of miR-27b were overexpressed in HCC. Overexpression
      of miR-27b was correlated with adverse prognostic features and reduced survival
      rate. Inhibition of miR-27b in SMMC-7721 cells remarkably suppressed
      proliferative ability and cell-cycle progression while enhanced apoptosis. In
      contrast, miR-27b overexpression resulted in prominent increased proliferation
      and process of cell cycle and reduced apoptosis of Hep3B cells. In vivo studies
      showed that knockdown of miR-27b inhibited the in vivo growth of SMMC-7721 cells
      in mouse xenograft model. Furthermore, we confirmed that Fbxw7 was directly
      regulated by miR-27b and mediated the roles of miR-27b in HCC. We suggest that
      miR-27b serves as an oncogenic miRNA in HCC by modulating proliferation, cell
      cycle progression, and apoptosis, and its oncogenic effect is mediated by its
      downstream target gene, Fbxw7.

PMID- 27704357
TI  - Analysis of expression and prognostic significance of vimentin and the response
      to temozolomide in glioma patients.
AB  - Gliomas are the most common primary intracranial malignant tumors in adults.
      Surgical resection followed by optional radiotherapy and chemotherapy is the
      current standard therapy for glioma patients. Vimentin, a protein of intermediate
      filament family, could maintain the cellular integrity and participate in several
      cell signal pathways to modulate the motility and invasion of cancer cells. The
      purpose of the present research was to identify the relationship between vimentin
      expression and clinical characteristics and detect the prognostic and predictive
      ability of vimentin in patients with glioma. To determine the expression of
      vimentin in glioma tissues, paraffin-embedded blocks from glioma patients by
      surgical resection were obtained and evaluated by immunohistochemistry. To
      further investigate the association of vimentin expression with survival, we
      employed mRNA expression of vimentin genes from the Chinese Glioma Genome Atlas
      (CGGA) and the GSE 16011 dataset. Kaplan-Meier analysis and Cox regression model
      were used to statistical analysis. We detected positive vimentin straining in 84
      % of high-grade compared to 47 % in low-grade glioma patients. Additionally,
      vimentin mRNA expression was correlated with glioma grade in both CGGA and
      GSE16011 dataset. Patients with low vimentin expression have longer survival than
      high expression. In multivariate analysis, vimentin was an independent
      significant prognostic factor for high-grade glioma patients. We also identified
      that glioblastoma patients with low vimentin expression had a better response to
      temozolomide therapy. Vimentin expression has a significant association with
      tumor grade and overall survival of high-grade glioma patients. Low vimentin
      expression may benefit from temozolomide therapy.

PMID- 27704358
TI  - A humanized chimeric antibody Hai178 targeted to the beta subunit of F1F0 ATP
      synthase.
AB  - Inhibition of tumor vasculature is an effective strategy for cancer therapy.
      Angiostatin could suppress tumor growth and metastasis by binding and inhibiting
      F1F0 ATP synthase on the endothelial cell surface. We previously screened a
      monoclonal antibody (McAb, McAb178-5G10), which specifically bound to ATPase on
      the surface of cells and showed an angiostatin-like activity. Here, we further
      generated a panel of CHO-mAb subclone stable expressing a humanized chimeric
      antibody from hybridoma cell McAb178-5G10 by gene engineer. And then, we
      successfully expressed the humanized antibody Hai178 at high level in a 5-L wave
      bioreactor. The vitro results showed that Hai178 retained the specific binding
      and antitumor activity of murine antibody. Furthermore, Hai178 also had a tumor
      therapeutic effect in tumor xenografts. These results paved the way for Hai178 as
      a therapeutic antibody in clinic.

PMID- 27704360
TI  - E2F-1 promotes DAPK2-induced anti-tumor immunity of gastric cancer cells by
      targeting miR-34a.
AB  - Activation of the transcription factor E2F-1 gene is a negative event in
      dendritic cell (DC) maturation process. Down-regulation of E2F1 causes immaturity
      of DC thereby stopping antigen production which in turn leads to inhibition of
      immune responses. E2F-1-free stimulates the NF-kB signaling pathway, leading to
      activation of monocytes and several other transcription factor genes. In the
      study, we report that down-regulation of E2F-1 in DCs promote anti-tumor immune
      response in gastric cancer (GC) cells through a novel mechanism. DCs were
      isolated from peripheral blood mononuclear cells. E2F-1 small interfering RNA
      (E2F-1-shRNA) induced down-regulation of E2F-1 mRNA and protein expression in
      DCs. Furthermore, we identified the E2F-1-shRNA targeted the CD80, CD83, CD86,
      and MHC II molecules, promoted their expression, and induced T lymphocytes
      proliferation activity and up-regulation of IFN-I3 production and GC cell killing
      effect, which significantly correlated with the cytotoxic T lymphocytes activated
      by E2F-1-shRNA DCs. The higher expression of miR-34a was found which was
      significantly correlated with the DC enhancing anti-tumor immunity against
      gastric cancer cell, and miR-34a potently targeted DAPK2 and Sp1, both of which
      were involved in the deactivation of E2F-1. Moreover, in E2F-1-DC-down-regulation
      in mice, GC transplantation tumors displayed down-regulation of Sp1, DAPK2,
      Caspase3, and Caspase7 and progressed to anti-tumor immunity. Collectively, our
      data uncover an E2F-1-mediated mechanism for the control of DC anti-tumor
      immunity via miR-34a-dependent down-regulation of E2F-1 expression and suggest
      its contribution to GC immunotherapy.

PMID- 27704359
TI  - Transcriptomic characterization of differential gene expression in oral squamous
      cell carcinoma: a meta-analysis of publicly available microarray data sets.
AB  - Oral squamous cell carcinoma (OSCC) is a highly prevalent cancer worldwide, and
      OSCC often goes undiagnosed until advanced disease is present, which contributes
      to a low survival rate for OSCC patients. The identification of biomarkers for
      the early detection OSCC and novel therapeutic targets for OSCC treatment is an
      important research objective. We performed bioinformatics analyses of the gene
      expression profile of OSCC using microarray data to identify genes that
      contribute to the development of OSCC. We also predicted the transcription
      factors involved in the regulation of differential gene expression in OSCC. Our
      results showed that PI3K, EGFR, STAT1, and CPBP are important contributors to the
      changes in cellular physiology that occur during the development of OSCC.
      Therefore, these genes represent potential diagnostic biomarkers and therapeutic
      targets for OSCC.

PMID- 27704362
TI  - Isolation and Culture of Adult Intestinal, Gastric, and Liver Organoids for Cre
      recombinase-Mediated Gene Deletion.
AB  - The discovery of Lgr5 as a marker of adult stem cells meant that stem cell
      populations could be purified and studied in isolation. Importantly, when
      cultured under the appropriate conditions these stem cells form organoids in
      tissue culture that retain many features of the tissue of origin. The organoid
      cultures are accessible to genetic and biochemical manipulation, bridging the gap
      between in vivo mouse models and conventional tissue culture. Here we describe
      robust protocols to establish organoids from gastrointestinal tissues (stomach,
      intestine, liver) and Cre-recombinase mediated gene manipulation in vitro.

PMID- 27704361
TI  - Association of single-nucleotide polymorphisms of high-mobility group box 1 with
      susceptibility and clinicopathological characteristics of uterine cervical
      neoplasia in Taiwanese women.
AB  - To date, no study associated the genetic polymorphisms of high-mobility group box
      1 protein (HMGB1) with the development of uterine cervical cancer. We therefore
      conducted this study to investigate the associations of HMGB1 single-nucleotide
      polymorphisms (SNPs) with cervical carcinogenesis and clinicopathological
      characteristics of cancer patients. Five hundred two women, including 112 with
      invasive cancer, 85 with precancerous lesions of the uterine cervix, and 305
      normal controls, were consecutively enrolled into this study. Analysis of HMGB1
      SNPs was done by real-time polymerase chain reaction and genotyping. Our results
      found that the risk of susceptibility to cervical invasive cancer was 1.85 (95 %
      CI 1.12-3.04; p = 0.016) in women with TC and 1.99 (95 % CI 1.24-3.23; p = 0.005)
      in women with TC/CC after adjusting for age, using TT as a comparison reference
      in HMGB1 SNP rs1412125. In rs2249825, the increased risk was also seen for the
      development of cervical invasive cancer in women with CG [adjusted odds ratio
      (AOR) 2.04, 95 % CI 1.22-3.40; p = 0.006] or CG/GG (AOR 2.02, 95 % CI 1.22-3.32;
      p = 0.006) using CC as a comparison reference. An additional integrated in silico
      analysis confirmed that rs2249825 creates a binding site for v-Myb, which may
      affect HMGB1 expression. In conclusion, Taiwanese women with TC or TC/CC in HMGB1
      SNP rs1412125 as well as CG or CG/GG in rs2249825 were susceptible to the
      development of cervical invasive cancer.

PMID- 27704363
TI  - Backbone 1H, 15N, and 13C resonance assignments of the Tom1 VHS domain.
AB  - Efficient trafficking of ubiquitinated receptors (cargo) to endosomes requires
      the recruitment of adaptor proteins that exhibit ubiquitin-binding domains for
      recognition and transport. Tom1 is an adaptor protein that not only associates
      with ubiquitinated cargo but also represents a phosphoinositide effector during
      specific bacterial infections. This phosphoinositide-binding property is
      associated with its N-terminal Vps27, Hrs, STAM (VHS) domain. Despite its
      biological relevance, there are no resonance assignments of Tom1 VHS available
      that can fully characterize its molecular interactions. Here, we report the
      nearly complete 1H, 15N, and 13C backbone resonance assignments of the VHS domain
      of human Tom1.

PMID- 27704364
TI  - Peer Review at JGIM.

PMID- 27704365
TI  - Providing Patient-Centered Care to Veterans of All Races: Challenges and Evidence
      of Success.

PMID- 27704366
TI  - Trade-Offs: Pros and Cons of Being a Doctor and Patient in Canada.

PMID- 27704367
TI  - SGIM-AMDA-AGS Consensus Best Practice Recommendations for Transitioning Patients'
      Healthcare from Skilled Nursing Facilities to the Community.
AB  - We assembled a cross-cutting team of experts representing primary care physicians
      (PCPs), home care physicians, physicians who see patients in skilled nursing
      facilities (SNF physicians), skilled nursing facility medical directors, human
      factors engineers, transitional care researchers, geriatricians, internists,
      family practitioners, and three major organizations: AMDA, SGIM, and AGS. This
      work was sponsored through a grant from the Association of Subspecialty
      Physicians (ASP). Members of the team mapped the process of discharging patients
      from a skilled nursing facility into the community and subsequent care of their
      outpatient PCP. Four areas of process improvement were identified, building on
      the prior work of the AMDA Transitions of Care Committee and the experiences of
      the team members. The team identified issues and developed best practices
      perceived as feasible for SNF physician and PCP practices to accomplish. The goal
      of these consensus-based recommended best practices is to provide a safe and high
      quality transition for patients moving between the care of their SNF physician
      and PCP.

PMID- 27704368
TI  - Development and Implementation of a Novel HIV Primary Care Track for Internal
      Medicine Residents.
AB  - BACKGROUND: Declining mortality has led to a rising number of persons living with
      HIV (PLWH) and concerns about a future shortage of HIV practitioners. AIM: To
      develop an HIV Primary Care Track for internal medicine residents. SETTING:
      Academic hospital and community health center with a history of caring for PLWH
      and lesbian, gay, bisexual, and transgender (LGBT) patients. PARTICIPANTS:
      Internal medicine residents. PROGRAM DESCRIPTION: We enrolled four residents
      annually in a 3-year track with the goal of having each provide continuity care
      to at least 20 PLWH. The curriculum included small group learning sessions,
      outpatient electives, a global health opportunity, and the development of a
      scholarly project. PROGRAM EVALUATION: All residents successfully accrued 20 or
      more PLWH as continuity patients. Senior residents passed the American Academy of
      HIV Medicine certification exam, and 75 % of graduates took positions in primary
      care involving PLWH. Clinical performance of residents in HIV care quality
      measures was comparable to those reported in published cohorts. DISCUSSION: We
      developed and implemented a novel track to train medical residents in the care of
      PLWH and LGBT patients. Our results suggest that a designated residency track can
      serve as a model for training the next generation of HIV practitioners.

PMID- 27704369
TI  - Development of Metabolic Syndrome Associated to Cancer Therapy: Review.
AB  - Long-term childhood cancer survivors are at great risk of developing late adverse
      effects after treatment, such as, reduced growth, obesity, decreased fertility,
      high blood pressure, cardiovascular diseases, impaired glucose, another form of
      cancer, among others organ dysfunctions, some of them are part of the metabolic
      syndrome. Metabolic syndrome and cancer connection is still not entirely
      understood, but there are some notions about it. Metabolic alterations produced
      during childhood cancer are more likely determined by treatments like
      radiotherapy, chemotherapy, glucocorticoids therapy, and surgery. Cancer
      treatment is associated to vascular alterations, hormone deficiencies, changes in
      insulin sensitivity, lipid metabolism, and inflammatory mediators. Obesity has
      been considered a crucial component in metabolic syndrome; obesity risk factors
      during childhood cancer include cranial radiation, female gender, and exposure to
      glucocorticoids such as dexamethasone. In addition, local radiotherapy or surgery
      may cause endocrine deficiencies, depends on the directly damage of endocrine
      organs. Patients who received some types of cancer treatment should be evaluated
      periodically to early diagnostic metabolic disorders associated to antineoplastic
      therapy.

PMID- 27704371
TI  - Esophageal Cancer Surgery for Patients with Concomitant Liver Cirrhosis: A Single
      Center Matched-Cohort Study.
AB  - BACKGROUND: Cirrhosis is a risk factor with nonhepatic surgery, but only three
      series regarding esophagectomy are reported. The Model for End-Stage Liver
      Disease (MELD) score has shown benefit in risk evaluation, but there is no
      experience regarding esophagectomy. This study aimed to compare the outcomes of
      surgery for esophageal cancer between cirrhotic and noncirrhotic patients and to
      evaluate whether the MELD score has a prognostic value for risk stratification.
      METHODS: From the authors' esophageal cancer database, they selected all the
      patients with concomitant cirrhosis who underwent surgery with curative intent
      and a matched cohort of patients without cirrhosis. The preoperative data
      included demographics, medical history, blood work, American Society of
      Anesthesiologists (ASA) score, Child-Turcotte-Pugh (CTP) score, and MELD score.
      The operative data included type of surgery, radicality, operative time, and
      blood loss. The postoperative data included hemoderivatives, 90-day morbidity and
      mortality rates, lab works, and hospital length of stay. The cirrhotic patients
      were further divided and analyzed according to a MELD score cutoff of 9. RESULTS:
      Of 3445 esophageal cancer patients, 73 cirrhotic patients underwent surgery.
      Their 90-day morbidity and mortality rates were higher than those for 146
      noncirrhotic patients. The cirrhotic patients also had more respiratory events (p
      = 0.013) and infections (p = 0.005). The anastomotic complications among the
      cirrhotic patients were significantly more severe (p = 0.046). No difference in 5
      year survival rates was registered. Stratification according to the MELD score
      showed that patients with a MELD score higher than 9 had a significantly worse
      postoperative course (5-year survival: p = 0.004). The patients with a MELD score
      of 9 or lower showed an outcome similar to that of the noncirrhotic patients.
      CONCLUSIONS: Liver cirrhosis is not an absolute contraindication to
      esophagectomy. The MELD score can be applicable for esophagectomy risk assessment
      for cirrhotic patients.

PMID- 27704372
TI  - Active Surveillance for DCIS: The Importance of Selection Criteria and
      Monitoring.

PMID- 27704370
TI  - Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy
      Recommendations for Patients with Ductal Carcinoma In Situ.
AB  - OBJECTIVE: The aim of this study was to determine the impact of the results of
      the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients
      with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery
      (BCS), and (ii) patient decisional conflict and state anxiety. METHODS: Thirteen
      sites across the US enrolled patients (March 2014-August 2015) with pure DCIS
      undergoing BCS. Prospectively collected data included clinicopathologic factors,
      physician estimates of local recurrence risk, DCIS Score results, and pre-/post
      assay radiotherapy recommendations for each patient made by a surgeon and a
      radiation oncologist. Patients completed pre-/post-assay decisional conflict
      scale and state-trait anxiety inventory instruments. RESULTS: The analysis cohort
      included 127 patients: median age 60 years, 80 % postmenopausal, median size 8 mm
      (39 % <=5 mm), 70 % grade 1/2, 88 % estrogen receptor-positive, 75 % progesterone
      receptor-positive, 54 % with comedo necrosis, and 18 % multifocal. Sixty-six
      percent of patients had low DCIS Score results, 20 % had intermediate DCIS Score
      results, and 14 % had high DCIS Score results; the median result was 21 (range 0
      84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for
      70.9 and 72.4 % of patients, respectively. Post-assay, 26.4 % of overall
      recommendations changed, including 30.7 and 22.0 % of recommendations by surgeons
      and radiation oncologists, respectively. Among patients with confirmed completed
      questionnaires (n = 32), decision conflict (p = 0.004) and state anxiety (p =
      0.042) decreased significantly from pre- to post-assay. CONCLUSIONS:
      Individualized risk estimates from the DCIS Score assay provide valuable
      information to physicians and patients. Post-assay, in response to DCIS Score
      results, surgeons changed treatment recommendations more often than radiation
      oncologists. Further investigation is needed to better understand how such
      treatment changes may affect clinical outcomes.

PMID- 27704373
TI  - Simulation of Deformation and Aggregation of Two Red Blood Cells in a Stenosed
      Microvessel by Dissipative Particle Dynamics.
AB  - The motion of two red blood cells in a stenosed microvessel was simulated using
      dissipative particle dynamics. The effects of intercellular interaction, red
      blood cell deformability and the initial cell orientation on the deformation and
      aggregation of the RBCs and on the flow resistance were investigated. The red
      blood cell membrane was treated as a three-dimensional coarse-grained network
      model and the intercellular interaction was modeled by the Morse potential based
      on a depletion-mediated assumption. It is shown that the flow resistance
      increases dramatically when the red blood cells enter into the stenosis and
      decreases rapidly as RBCs move away from the stenosis. Particularly, for a pair
      of stiffer red blood cells with the initial inclination angle of 90 degrees , the
      maximum value of the flow resistance is larger; while a higher flow resistance
      can also come from a stronger aggregation. For a pair of stiffer red blood cells
      moving parallel to the main flow, when their positions are closer to the vessel
      wall at the upstream of the stenosis, the flow resistance increases due to the
      migration to the vessel center at the stenosis. In addition, for a pair of red
      blood cells with the initial inclination angle of 0 degrees , the flow resistance
      from the aggregate formed by a pair of red blood cells with a larger deformation
      is higher.

PMID- 27704374
TI  - Biocompatible nano-gallium/hydroxyapatite nanocomposite with antimicrobial
      activity.
AB  - Intensive research in the area of medical nanotechnology, especially to cope with
      the bacterial resistance against conventional antibiotics, has shown strong
      antimicrobial action of metallic and metal-oxide nanomaterials towards a wide
      variety of bacteria. However, the important remaining problem is that
      nanomaterials with highest antibacterial activity generally express also a high
      level of cytotoxicity for mammalian cells. Here we present gallium nanoparticles
      as a new solution to this problem. We developed a nanocomposite from bioactive
      hydroxyapatite nanorods (84 wt %) and antibacterial nanospheres of elemental
      gallium (16 wt %) with mode diameter of 22 +/- 11 nm. In direct comparison, such
      nanocomposite with gallium nanoparticles exhibited better antibacterial
      properties against Pseudomonas aeruginosa and lower in-vitro cytotoxicity for
      human lung fibroblasts IMR-90 and mouse fibroblasts L929 (efficient antibacterial
      action and low toxicity from 0.1 to 1 g/L) than the nanocomposite of
      hydroxyapatite and silver nanoparticles (efficient antibacterial action and low
      toxicity from 0.2 to 0.25 g/L). This is the first report of a biomaterial
      composite with gallium nanoparticles. The observed strong antibacterial
      properties and low cytotoxicity make the investigated material promising for the
      prevention of implantation-induced infections that are frequently caused by P.
      aeruginosa.

PMID- 27704375
TI  - Enhancement of mechanical properties of 3D printed hydroxyapatite by combined low
      and high molecular weight polycaprolactone sequential infiltration.
AB  - A new infiltration technique using a combination of low and high molecular weight
      polycaprolactone (PCL) in sequence was developed as a mean to improve the
      mechanical properties of three dimensional printed hydroxyapatite (HA). It was
      observed that using either high (M n~80,000) or low (M n~10,000) molecular weight
      infiltration could only increase the flexural modulus compared to non-infiltrated
      HA, but did not affect strength, strain at break and energy at break. In
      contrast, a combination of low and high molecular infiltration in sequence
      increased the flexural modulus, strength and energy at break compared to those of
      non-infiltrated HA or infiltrated by high or low molecular weight PCL alone. This
      overall enhancement was found to be attributed to the densification of low
      molecular weight PCL and the reinforcement of high molecular PCL concurrently.
      The combined low and high molecular weight infiltration in sequence also
      maintained high osteoblast proliferation and differentiation of the composites at
      the similar level of the HA. Densification was a dominant mechanism for the
      change in modulus with porosity and density of the infiltrated HA/PCL composites.
      However, both densification and the reinforcing performance of the infiltration
      phase were crucial for strength and toughening enhancement of the composites
      possibly by the defect healing and stress shielding mechanisms. The sequence of
      using low molecular weight infiltration and followed by high molecular
      infiltration was seen to provide the greatest flexural properties and highest
      cells proliferation and differentiation capabilities.

PMID- 27704376
TI  - Synthesis of Ag doped calcium phosphate particles and their antibacterial effect
      as additives in dental glass ionomer cements.
AB  - Developing dental restorations with enhanced antibacterial properties has been a
      constant quest for materials scientists. The aim of this study was to synthesize
      silver doped calcium phosphate particles and use them to improve antibacterial
      properties of conventional glass ionomer cement. The Ag doped monetite (Ag-DCPA)
      and hydroxyapatite (Ag-HA) were synthesized by precipitation method and
      characterized using X-ray diffraction, scanning electron microscope and X-ray
      fluorescence spectroscopy. The antibacterial properties of the cements aged for 1
      day and 7 days were evaluated by direct contact measurement using staphylococcus
      epidermis Xen 43. Ion concentrations (F- and Ag+) and pH were measured to
      correlate to the results of the antibacterial study. The compressive strength of
      the cements was evaluated with a crosshead speed of 1 mm/min. The glass ionomer
      cements containing silver doped hydroxyapatite or monetite showed improved
      antibacterial properties. Addition of silver doped hydroxyapatite or monetite did
      not change the pH and ion release of F-. Concentration of Ag+ was under the
      detection limit (0.001 mg/L) for all samples. Silver doped hydroxyapatite or
      monetite had no effect on the compressive strength of glass ionomer cement.

PMID- 27704377
TI  - Development of a protocol to optimize electric power consumption and life cycle
      environmental impacts for operation of wastewater treatment plant.
AB  - In wastewater treatment plants (WWTPs), the portion of operating costs related to
      electric power consumption is increasing. If the electric power consumption
      decreased, however, it would be difficult to comply with the effluent water
      quality requirements. A protocol was proposed to minimize the environmental
      impacts as well as to optimize the electric power consumption under the
      conditions needed to meet the effluent water quality standards in this study.
      This protocol was comprised of six phases of procedure and was tested using
      operating data from S-WWTP to prove its applicability. The 11 major operating
      variables were categorized into three groups using principal component analysis
      and K-mean cluster analysis. Life cycle assessment (LCA) was conducted for each
      group to deduce the optimal operating conditions for each operating state. Then,
      employing mathematical modeling, six improvement plans to reduce electric power
      consumption were deduced. The electric power consumptions for suggested plans
      were estimated using an artificial neural network. This was followed by a second
      round of LCA conducted on the plans. As a result, a set of optimized improvement
      plans were derived for each group that were able to optimize the electric power
      consumption and life cycle environmental impact, at the same time. Based on these
      test results, the WWTP operating management protocol presented in this study is
      deemed able to suggest optimal operating conditions under which power consumption
      can be optimized with minimal life cycle environmental impact, while allowing the
      plant to meet water quality requirements.

PMID- 27704378
TI  - Columnar aerosol characteristics and radiative forcing over the Doon Valley in
      the Shivalik range of northwestern Himalayas.
AB  - Spectral aerosol optical depth (AOD) measurements obtained from multi-wavelength
      radiometer under cloudless conditions over Doon Valley, in the foothills of the
      western Himalayas, are analysed during the period January 2007 to December 2012.
      High AOD values of 0.46 +/- 0.08 and 0.52 +/- 0.1 at 500 nm, along with low
      values of Angstrom exponent (0.49 +/- 0.01 and 0.44 +/- 0.03) during spring
      (March-May) and summer (June-August), respectively, suggest a flat AOD spectrum
      indicative of coarse-mode aerosol abundance compared with winter (December
      February) and autumn (September-November), which are mostly dominated by fine
      aerosols from urban/industrial emissions and biomass burning. The columnar size
      distributions (CSD) retrieved from the King's inversion of spectral AOD exhibit
      bimodal size patterns during spring and autumn, while combinations of the power
      law and unimodal distributions better simulate the retrieved CSDs during winter
      and summer. High values of extinction coefficient near the surface (~0.8-1.0 km-1
      at 532 nm) and a steep decreasing gradient above are observed via CALIPSO
      profiles in autumn and winter, while spring and summer exhibit elevated aerosol
      layers between ~1.5 and 3.5 km due to the presence of dust. The particle
      depolarisation ratio shows a slight increasing trend with altitude, with higher
      values in spring and summer indicative of non-spherical particles of dust origin.
      The aerosol-climate implications are evaluated via the aerosol radiative forcing
      (ARF), which is estimated via the synergy of OPAC and SBDART models. On the
      monthly basis, the ARF values range from ~ -30 to -90 W m-2 at the surface, while
      aerosols cause an overall cooling effect at the top of atmosphere (approx. -5 to 
      15 W m-2). The atmospheric heating via aerosol absorption results in heating
      rates of 1.2-1.6 K day-1 during March-June, which may contribute to changes in
      monsoon circulation over northern India and the Himalayas.

PMID- 27704379
TI  - Photocatalytic degradation of methylene blue dye by zinc oxide nanoparticles
      obtained from precipitation and sol-gel methods.
AB  - Zinc oxide (ZnO) nanoparticles were synthesized by precipitation and sol-gel
      methods. The aim of this study was to understand how different synthetic methods
      can affect the photocatalytic activity of ZnO nanoparticles. As-synthesized ZnO
      nanoparticles were characterized by X-ray diffraction (XRD) and UV-Visible
      spectroscopic techniques. XRD patterns of ZnO powders synthesized by
      precipitation and sol-gel methods revealed their hexagonal wurtzite structure
      with crystallite sizes of 30 and 28 nm, respectively. Their photocatalytic
      activities were evaluated by photocatalytic degradation of methylene blue, a
      common water pollutant, under UV radiation. The effects of operational parameters
      such as photocatalyst load and initial concentration of the dye on photocatalytic
      degradation of methylene blue were investigated. While the degradation of dye
      decreased over the studied dye concentration range of 20 to 100 mg/L, an optimum
      photocatalyst load of 250 mg/L was needed to achieve dye degradation as high as
      81 and 92.5 % for ZnO prepared by precipitation and sol-gel methods,
      respectively. Assuming pseudo first-order reaction kinetics, this corresponded to
      rate constants of 8.4 * 10-3 and 12.4 * 10-3 min-1, respectively. Hence, sol-gel
      method is preferred over precipitation method in order to achieve higher
      photocatalytic activity of ZnO nanostructures. Photocatalytic activity is further
      augmented by better choice of capping ligand for colloidal stabilization, starch
      being more effective than polyethylene glycol (PEG).

PMID- 27704380
TI  - Novel insights into the metabolic pathway of iprodione by soil bacteria.
AB  - Microbial degradation constitutes the key soil dissipation process for iprodione.
      We recently isolated a consortium, composed of an Arthrobacter sp. strain C1 and
      an Achromobacter sp. strain C2, that was able to convert iprodione to 3,5
      dichloroaniline (3,5-DCA). However, the formation of metabolic intermediates and
      the role of the strains on iprodione metabolism remain unknown. We examined the
      degradation of iprodione and its suspected metabolic intermediates, 3,5
      dichlorophenyl-carboxamide (metabolite I) and 3,5-dichlorophenylurea-acetate
      (metabolite II), by strains C1 and C2 and their combination under selective (MSM)
      and nutrient-rich conditions (LB). Bacterial growth during degradation of the
      tested compounds was determined by qPCR. Strain C1 rapidly degraded iprodione
      (DT50 = 2.3 h) and metabolite II (DT50 = 2.9 h) in MSM suggesting utilization of
      isopropylamine, transiently formed by hydrolysis of iprodione, and glycine
      liberated during hydrolysis of metabolite II, as C and N sources. In contrast,
      strain C1 degraded metabolite I only in LB and growth kinetics suggested the
      involvement of a detoxification process. Strain C2 was able to transform
      iprodione and its metabolites only in LB. Strain C1 degraded vinclozolin, a
      structural analog of iprodione, and partially propanil, but not procymidone and
      phenylureas indicating a structure-dependent specificity related to the
      substituents of the carboxamide moiety.

PMID- 27704381
TI  - Trend and variability of atmospheric ozone over middle Indo-Gangetic Plain:
      impacts of seasonality and precursor gases.
AB  - Ozone dynamics in two urban background atmospheres over middle Indo-Gangetic
      Plain (IGP) were studied in two contexts: total columnar and ground-level ozone.
      In terms of total columnar ozone (TCO), emphases were made to compare satellite
      based retrieval with ground-based observation and existing trend in decadal and
      seasonal variation was also identified. Both satellite-retrieved (Aura Ozone
      Monitoring Instrument-Differential Optical Absorption Spectroscopy (OMI-DOAS))
      and ground-based observations (IMD-O3) revealed satisfying agreement with OMI
      DOAS observation over predicting TCO with a positive bias of 7.24 % under all-sky
      conditions. Minor variation between daily daytime (r = 0.54; R 2 = 29 %; n = 275)
      and satellite overpass time-averaged TCO (r = 0.58; R 2 = 34 %; n = 208) was also
      recognized. A consistent and clear seasonal trend in columnar ozone (2005-2015)
      was noted with summertime (March-June) maxima (Varanasi, 290.9 +/- 8.8; Lucknow,
      295.6 +/- 9.5 DU) and wintertime (December-February) minima (Varanasi, 257.4 +/-
      10.1; Lucknow, 258.8 +/- 8.8 DU). Seasonal trend decomposition based on locally
      weighted regression smoothing technique identified marginally decreasing trend
      (Varanasi, 0.0084; Lucknow, 0.0096 DU year-1) especially due to reduction in
      monsoon time minima and summertime maxima. In continuation to TCO, variation in
      ground-level ozone in terms of seasonality and precursor gases were also analysed
      from September 2014 to August 2015. Both stations registered similar pattern of
      variation with Lucknow representing slightly higher annual mean (44.3 +/- 30.6;
      range, 1.5-309.1 MUg/m3) over Varanasi (38.5 +/- 17.7; range, 4.9-104.2 MUg/m3).
      Variation in ground-level ozone was further explained in terms water vapour,
      atmospheric boundary layer height and solar radiation. Ambient water vapour
      content was found to associate negatively (r = -0.28, n = 284) with ground-level
      ozone with considerable seasonal variation in Varanasi. Implication of solar
      radiation on formation of ground-level ozone was overall positive (Varanasi,
      0.60; Lucknow, 0.26), while season-specific association was recorded in case of
      atmospheric boundary layer.

PMID- 27704382
TI  - Cleaner processing: a sulphide-free approach for depilation of skins.
AB  - The conventional unhairing process in leather making utilises large amount of
      lime and sodium sulphide which is hazardous and poses serious waste disposal
      concerns. Under acidic conditions, sodium sulphide liberates significant
      quantities of hydrogen sulphide which causes frequent fatal accidents. Further,
      the conventional unhairing process involves destruction of the hair leading to
      increased levels of biological oxygen demand (BOD), chemical oxygen demand (COD),
      total dissolved solids (TDS) and total suspended solids (TSS) in the effluent. A
      safe approach is needed to overcome such environmental and health problems
      through an eco-benign process. The present study deals with a clean technology in
      which the keratinous body is detached from the dermis using enzymes produced from
      Bacillus crolab MTCC 5468 by solid state fermentation (SSF) as an alternative to
      noxious chemicals. Complete unhairing of skin could be achieved with an enzyme
      concentration of 1.2 % (w/w). The bio-chemical parameters of the spent liquor of
      the enzymatic process were environmentally favourable when compared with
      conventional method. The study indicates that the enzymatic unhairing is a safe
      process which could be used effectively in leather processing to alleviate
      pollution and health problems.

PMID- 27704383
TI  - Dissipation and residue of clothianidin in granules and pesticide fertilizers
      used in cabbage and soil under field conditions.
AB  - The single application of 0.5 % clothianidin granules, a novel formulation, was
      used to control pests in vegetables under a high dose. In this article, residues
      of clothianidin in cabbage and soil samples under field conditions from
      Guangzhou, Nanning, and Qianjiang were determined by HPLC. The terminal residues
      of clothianidin in cabbage were less than the limit of detection (<LOD) at pre
      harvest intervals of 30 days, and these values were lower than the maximum
      residue limit of 0.2 mg kg-1 in cabbage set by the Codex Alimentarius Commission.
      To test on the influence of the pesticide fertilizers' effect on clothianidin
      residual, clothianidin granules and fertilizers of chicken manure, urea, and
      organic fertilizer were mixed into different pesticide fertilizers through their
      normal field using dosage and evaluate residual influence of clothianidin in
      different formula. After analysis of variance of the effect factors, the effect
      of different pesticide types on half-life was not significant, but the effect of
      sample types was significant. Clothianidin granules and pesticide fertilizers
      could be safely applied in cabbage under a single high-dose administration.

PMID- 27704384
TI  - Neighborhood Context and Preterm Delivery among African American Women: the
      Mediating Role of Psychosocial Factors.
AB  - Preterm delivery (PTD), or birth before 37 completed weeks of gestation, is a
      serious public health issue, and racial disparities persist. In a recently
      published study, perceptions of the residential environment (or neighborhood
      context) were associated with PTD rates among urban African American women with
      low educational attainment (<=12 years); however, the mechanisms of these
      associations are unknown. Given this gap in the literature, we used data from the
      Life Influences on Fetal Environments Study of postpartum African American women
      from Metropolitan Detroit, Michigan (2009-2011; n = 399), to examine whether
      psychosocial factors (depressive symptomology, psychological distress, and
      perceived stress) mediate associations between perceptions of the neighborhood
      context and PTD. Validated scales were used to measure women's perceptions of
      their neighborhood safety, walkability, healthy food availability
      (higher=better), and social disorder (higher=more disorder). The psychosocial
      indicators were measured with the Center for Epidemiologic Studies-Depression
      Scale, Kessler's Psychological Distress Scale (K6), and Cohen's Perceived Stress
      Scale. Statistical mediation was assessed using an unadjusted logistic regression
      based path analysis for estimating direct and indirect effects. The associations
      between perceived walkability, food availability, and social disorder were not
      mediated by psychosocial factors. However, perceptions of neighborhood safety
      were inversely associated with depressive symptoms which were positively
      associated with PTD rates. Also, higher perceived neighborhood social disorder
      was associated with higher PTD rates, net of the indirect paths through
      psychosocial factors. Future research should identify other mechanisms of the
      perceived neighborhood context-PTD associations, which would inform PTD
      prevention efforts among high-risk groups.

PMID- 27704385
TI  - Thyroglossal Duct Cyst Carcinomas: A Clinicopathologic Series of 22 Cases with
      Staging Recommendations.
AB  - Carcinomas arising from thyroglossal duct remnant cysts (TGDCs) are rare, without
      well-defined management and staging criteria. All TGDCs (n = 685) diagnosed
      between 2005 and 2015 were retrospectively reviewed, with 22 carcinomas
      identified (3.2 % incidence). Twenty-two patients (17 females, 5 males), aged 12
      64 years (mean 39.9 years; median 39 years) were identified. An anterior,
      superior midline neck mass was the presenting symptom in all patients. A cancer
      diagnosis [all papillary thyroid carcinoma (PTC)] was made after the Sistrunk
      procedure (SP), with a Bethesda Category V or VI classification preoperatively by
      fine needle aspiration in 5 of 12 cases tested. A SP was performed in all
      patients, with total thyroidectomy concurrently (n = 4) or subsequently (n = 12).
      A selected neck dissection was performed in 5 patients, with metastases found in
      3. Of the patients who had a thyroidectomy, synchronous PTC was identified in 6
      (thus, 6 of 22 patients had synchronous thyroid gland primaries). This supports
      an origin from extra-thyroidal remnants (cyst origin) rather than metastatic
      tumor from a thyroid gland primary. Follow-up radioactive iodine therapy was
      performed in 13 patients. Metastatic disease to local lymph nodes 57 months after
      presentation was seen in 1 patient, with all others alive and disease free (mean
      3.8 years; range 0.4-10.8 years). The TGDCs ranged from 0.8 to 5 cm (mean 2.3
      cm), while the PTCs ranged from 0.1 to 3.8 cm (mean 1.4 cm). All of the tumors
      were classical PTC, showing a sclerotic and infiltrative pattern, with a capsule
      present in 11. Lymphovascular invasion was detected in 11; margins were positive
      in 6. Using currently defined criteria, the patients were separated into AJCC
      stage group I (n = 21) or II (n = 1). However, if extension into the adipose
      tissue (n = 11), skeletal muscle (n = 10), or perineural/perivascular tissues (n
      = 10) were used to stage the patients, interpreted to represent the equivalent of
      "extrathyroidal extension" (n = 13) as defined for thyroid gland primaries, there
      would be 15 group I and 7 group III cases. All seven group III patients were >=45
      years. Three of four patients with lymph node metastasis also showed soft tissue
      extension. In conclusion, TGDC carcinomas (TGDCCa) are uncommon, with all
      classical PTC. For "microcarcinomas" (<=1 cm), conservative management can be
      used for patients <45 years (i.e., Sistrunk procedure only); for >1 cm tumors,
      and due to the high incidence of concurrent papillary carcinoma and higher stage
      at presentation in older patients, completion thyroidectomy is recommended for
      patients >=45 years. Thus, even though a good prognosis can be expected for PTC
      developing in TGDCs, staging is advocated to more appropriately match therapeutic
      interventions.

PMID- 27704387
TI  - Differences in Patterns of Mortality Between Foreign-Born and Native-Born Workers
      Due to Fatal Occupational Injury in the USA from 2003 to 2010.
AB  - This study assesses differences mortality patterns and relative hazard due to
      fatal occupational injuries between native and immigrant workers in the US. Fatal
      occupational injury data from 2003 to 2010 were examined using survival analysis
      based on proportional hazards models controlling for categorical variables of
      race, gender, occupation, and industry. Workers are stratified based on whether
      they are native to the US (n = 31952) or born abroad (n = 7096). Foreign-born
      workers are further stratified into region of birth. Foreign-born workers had an
      adjusted hazard ratio of 1.148 (95 % CI 1.109:1.189) relative to native workers.
      Stratifying foreign-born workers into region of origin revealed significantly
      higher adjusted risk of work fatality relative to native workers for most foreign
      regions. Of fatally injured workers, foreign-born workers have shorter survival
      before succumbing to traumatic injury during their time of occupational
      'exposure' in the workforce. Native-born workers tend to incur fatal injuries at
      older ages after longer 'exposure'.

PMID- 27704386
TI  - Molecular and histologic characteristics of pseudoprogression in diffuse gliomas.
AB  - During the 6 month period following chemoradiotherapy, gliomas frequently develop
      new areas of contrast enhancement, which are due to treatment effect rather than
      tumor progression. We sought to characterize this phenomenon in
      oligodendrogliomas (OG) and mixed oligoastrocytomas (MOA). We reviewed the
      imaging findings from 143 patients with a WHO grade II or III OG or MOA for
      evidence of pseudoprogression (PsP) or early tumor progression. We characterized
      these cases for 1p/19q codeletions by FISH, IDH1 R132H mutation by
      immunohistochemistry, and TP53, ATRX, and EGFR mutations by next generation
      sequencing. We then reviewed the pathologic specimens of the patient cases in
      which a re-resection was performed. We found that OG and MOA that are 1p/19q
      intact developed PsP at a higher rate than tumors that are 1p/19q codeleted (27
      vs. 8 %). Moreover, IDH1 wild-type (WT) tumors developed PsP at a higher rate
      than IDH1 R132H cases (27 vs. 11 %). Patients with ATRX or TP53 mutations
      developed PsP at an intermediate rate of 21 %. Ten patients in our cohort
      underwent a re-resection for early contrast enhancement; these tumors were
      predominantly 1p/19q intact (90 %) and had a low rate of IDH1 R132H mutation (50
      %). 8 of 10 tumors demonstrated primarily treatment effects, while the remaining
      2 of 10 demonstrated recurrent/residual tumor of the same grade. Early contrast
      enhancement that develops during the first 6 months after chemoradiotherapy is
      typically due to PsP and occurs primarily in OG and MOA that are 1p/19q intact
      and IDH WT.

PMID- 27704388
TI  - Primary Care Screening Methods and Outcomes for Asylum Seekers in New York City.
AB  - Effective screening in primary care among asylum-seekers in the US is critical as
      this population grows. This study aimed to evaluate disease prevalence and
      screening methods in this high-risk group. Two hundred ten new clients from 51
      countries, plus Tibet, who were accepted into a program for asylum seekers from
      2012 to 2014 were included. Screening rates and outcomes for infectious, non
      communicable, and mental illnesses were evaluated. Screening rates were highest
      for PTSD, depression, hepatitis B, and latent tuberculosis. Seventy-one percent
      of clients screened positive for depression and 55 % for PTSD, followed by latent
      tuberculosis (41 %), hypertension (10 %), hepatitis B (9.4 %), and HIV (0.8 %).
      Overall screening rates were high. Point of care testing was more effective than
      testing that required a repeat visit. A large psychiatric and infectious disease
      burden was identified. These findings can inform future primary care screening
      efforts for asylum seekers in the US.

PMID- 27704390
TI  - Utility Estimates of Disease-Specific Health States in Prostate Cancer from Three
      Different Perspectives.
AB  - OBJECTIVE: To develop a statistical model generating utility estimates for
      prostate cancer specific health states, using preference weights derived from the
      perspectives of prostate cancer patients, men at risk for prostate cancer, and
      society. METHODS: Utility estimate values were calculated using standard gamble
      (SG) methodology. Study participants valued 18 prostate-specific health states
      with the five attributes: sexual function, urinary function, bowel function,
      pain, and emotional well-being. Appropriateness of model (linear regression,
      mixed effects, or generalized estimating equation) to generate prostate cancer
      utility estimates was determined by paired t-tests to compare observed and
      predicted values. Mixed-corrected standard SG utility estimates to account for
      loss aversion were calculated based on prospect theory. RESULTS: 132 study
      participants assigned values to the health states (n = 40 men at risk for
      prostate cancer; n = 43 men with prostate cancer; n = 49 general population). In
      total, 792 valuations were elicited (six health states for each 132
      participants). The most appropriate model for the classification system was a
      mixed effects model; correlations between the mean observed and predicted utility
      estimates were greater than 0.80 for each perspective. CONCLUSIONS: Developing a
      health-state classification system with preference weights for three different
      perspectives demonstrates the relative importance of main effects between
      populations. The predicted values for men with prostate cancer support the
      hypothesis that patients experiencing the disease state assign higher utility
      estimates to health states and there is a difference in valuations made by
      patients and the general population.

PMID- 27704389
TI  - The duration of acute kidney injury after cardiac surgery increases the risk of
      long-term chronic kidney disease.
AB  - BACKGROUND: Acute kidney injury (Dasta et al., Nephrol Dial Transplant 23(6):1970
      1974, 2008) following cardiac surgery is associated with higher perioperative
      morbidity and mortality, but its impact on long term development of chronic
      kidney disease (CKD) is uncertain. METHODS: A total of 350 patients submitted to
      elective cardiac surgery were evaluated for AKI, defined as an increase in serum
      creatinine (SCr) >= 0.3 mg/dL over baseline value. Univariate and multivariate
      analysis were used to study pre, intra and postoperative parameters associated
      with occurrence CKD after 12 months of follow-up. RESULTS: AKI incidence was 41 %
      (n = 88). The 12-month prevelence of CKD was 9 % (n = 19) in non-AKI patients
      versus 25 % (n = 54, p < 0.0001) in the AKI group. The factors identified as
      independent risk factors for long-term CKD development in the multivariate
      logistic regression model were age >60 years, hospitalization serum creatinine
      >0.8 mg/dL, peripheral artery disease, hemorrhage and AKI duration > 3 days.
      CONCLUSION: Patients developing AKI after cardiac surgery presented high
      prevalence of long-term incident CKD. The duration of AKI was a strong
      independent risk factor for this late CKD development. Recognition of predictive
      factors for CKD development following cardiac surgery-associated AKI may help to
      develop strategies to prevent or halt CKD progression in this population.

PMID- 27704391
TI  - The Conundrum of Modern Art : Prestige-Driven Coevolutionary Aesthetics Trumps
      Evolutionary Aesthetics among Art Experts.
AB  - Two major mechanisms of aesthetic evolution have been suggested. One focuses on
      naturally selected preferences (Evolutionary Aesthetics), while the other
      describes a process of evaluative coevolution whereby preferences coevolve with
      signals. Signaling theory suggests that expertise moderates these mechanisms. In
      this article we set out to verify this hypothesis in the domain of art and use it
      to elucidate Western modern art's deviation from naturally selected preferences.
      We argue that this deviation is consistent with a Coevolutionary Aesthetics
      mechanism driven by prestige-biased social learning among art experts. In order
      to test this hypothesis, we conducted two studies in which we assessed the
      effects on lay and expert appreciation of both the biological relevance of the
      given artwork's depicted content, viz., facial beauty, and the prestige specific
      to the artwork's associated context (MoMA). We found that laypeople appreciate
      artworks based on their depictions of facial beauty, mediated by aesthetic
      pleasure, which is consistent with previous studies. In contrast, experts
      appreciate the artworks based on the prestige of the associated context, mediated
      by admiration for the artist. Moreover, experts appreciate artworks depicting
      neutral faces to a greater degree than artworks depicting attractive faces. These
      findings thus corroborate our contention that expertise moderates the
      Evolutionary and Coevolutionary Aesthetics mechanisms in the art domain.
      Furthermore, our findings provide initial support for our proposal that prestige
      driven coevolution with expert evaluations plays a decisive role in modern art's
      deviation from naturally selected preferences. After discussing the limitations
      of our research as well as the relation that our results bear on cultural
      evolution theory, we provide a number of suggestions for further research into
      the potential functions of expert appreciation that deviates from naturally
      selected preferences, on the one hand, and expertise as a moderator of these
      mechanisms in other cultural domains, on the other.

PMID- 27704392
TI  - Ancestry Testing and the Practice of Genetic Counseling.
AB  - Ancestry testing is a home DNA test with many dimensions; in some cases, the
      implications and outcomes of testing cross over into the health sphere. Common
      reasons for seeking ancestry testing include determining an estimate of
      customer's ethnic background, identifying genetic relatives, and securing a raw
      DNA data file that can be used for other purposes. As the ancestry test
      marketplace continues to grow, and third-party vendors empower the general public
      to analyze their own genetic material, the role of the genetic counselor is
      likely to evolve dramatically. Roles of the genetic counselor may include
      assisting clients with the interpretation of and adaptation to these results, as
      well as advising the companies involved in this sector on the ethical, legal, and
      social issues associated with testing. This paper reviews the history,
      fundamentals, intended uses, and unintended consequences of ancestry genetic
      testing. It also discusses the types of information in an ancestry testing
      result, situations that might involve a clinical genetic counselor, and the
      benefits, limitations, and functions that ancestry genetic testing can play in a
      clinical genetics setting.

PMID- 27704393
TI  - Effects of Type 1 Diabetes on Osteoblasts, Osteocytes, and Osteoclasts.
AB  - PURPOSE OF REVIEW: To describe the effects of type 1 diabetes on bone cells.
      RECENT FINDINGS: Type 1 diabetes (T1D) is associated with low bone mineral
      density, increased risk of fractures, and poor fracture healing. Its effects on
      the skeleton were primarily attributed to impaired bone formation, but recent
      data suggests that bone remodeling and resorption are also compromised. The
      hyperglycemic and inflammatory environment associated with T1D impacts
      osteoblasts, osteocytes, and osteoclasts. The mechanisms involved are complex;
      insulinopenia, pro-inflammatory cytokine production, and alterations in gene
      expression are a few of the contributing factors leading to poor osteoblast
      activity and survival and, therefore, poor bone formation. In addition, the
      observed sclerostin level increase accompanied by decreased osteocyte number and
      enhanced osteoclast activity in T1D results in uncoupling of bone remodeling. T1D
      negatively impacts osteoblasts and osteocytes, whereas its effects on osteoclasts
      are not well characterized, although the limited studies available indicate
      increased osteoclast activity, favoring bone resorption.

PMID- 27704394
TI  - Bone Microarchitecture in Type 1 Diabetes: It Is Complicated.
AB  - Patients with type 1 diabetes (T1DM) experience a disproportionate number of
      fractures for their bone mineral density (BMD). Differences in bone
      microarchitecture from those without the disease are thought to be responsible.
      However, the literature is inconclusive. New studies of the microarchitecture
      using three-dimensional imaging have the advantage of providing in vivo estimates
      of "bone quality," rather than examining areal BMD alone. There are drawbacks in
      that most studies have been done on those with less than a 30-year duration of
      T1DM, and the techniques used to measure vary as do the sites assessed. In
      addition to the rise in these imaging techniques, very recent literature presents
      evidence of an intimate relationship between skeletal health and vascular
      complications in T1DM. The following review provides an overview of the available
      studies of the bone microarchitecture in T1DM with a discussion of the burgeoning
      field of complications and skeletal health.

PMID- 27704397
TI  - ?

PMID- 27704395
TI  - Recent Tissue Engineering Advances for the Treatment of Temporomandibular Joint
      Disorders.
AB  - Temporomandibular disorders (TMDs) are among the most common maxillofacial
      complaints and a major cause of orofacial pain. Although current treatments
      provide short- and long-term relief, alternative tissue engineering solutions are
      in great demand. Particularly, the development of strategies, providing long-term
      resolution of TMD to help patients regain normal function, is a high priority. An
      absolute prerequisite of tissue engineering is to understand normal structure and
      function. The current knowledge of anatomical, mechanical, and biochemical
      characteristics of the temporomandibular joint (TMJ) and associated tissues will
      be discussed, followed by a brief description of current TMD treatments. The main
      focus is on recent tissue engineering developments for regenerating TMJ tissue
      components, with or without a scaffold. The expectation for effectively managing
      TMD is that tissue engineering will produce biomimetic TMJ tissues that
      recapitulate the normal structure and function of the TMJ.

PMID- 27704396
TI  - Advanced Glycation End Products, Diabetes, and Bone Strength.
AB  - Diabetic patients have a higher fracture risk than expected by their bone mineral
      density (BMD). Poor bone quality is the most suitable and explainable cause for
      the elevated fracture risk in this population. Advanced glycation end products
      (AGEs), which are diverse compounds generated via a non-enzymatic reaction
      between reducing sugars and amine residues, physically affect the properties of
      the bone material, one of a component of bone quality, through their accumulation
      in the bone collagen fibers. On the other hand, these compounds biologically act
      as agonists for these receptors for AGEs (RAGE) and suppress bone metabolism. The
      concentrations of AGEs and endogenous secretory RAGE, which acts as a "decoy
      receptor" that inhibits the AGEs-RAGE signaling axis, are associated with
      fracture risk in a BMD-independent manner. AGEs are closely associated with the
      pathogenesis of this unique clinical manifestation through physical and
      biological mechanisms in patients with diabetes mellitus.

PMID- 27704398
TI  - The RET E616Q Variant is a Gain of Function Mutation Present in a Family with
      Features of Multiple Endocrine Neoplasia 2A.
AB  - The REarranged during Transfection (RET) proto-oncogene is a receptor tyrosine
      kinase involved in growth and differentiation during embryogenesis and
      maintenance of the urogenital and nervous systems in mammals. Distinct mutations
      across hotspot RET exons can cause Multiple Endocrine Neoplasia Type 2A (MEN2A)
      characterised by development of medullary thyroid cancer (MTC), phaeochromocytoma
      (PCC) and primary hyperparathyroidism (PHPT), with a strong correlation between
      genotype and phenotype. Here, we report a 42-year-old man presented in the clinic
      with a unilateral PCC, with subsequent investigations revealing a nodular and
      cystic thyroid gland. He proceeded to thyroidectomy, which showed bilateral C
      cell hyperplasia (CCH) without evidence of MTC. His brother had neonatal
      Hirschsprung disease (HSCR). Genetic testing revealed the presence of a
      heterozygous variant of unknown significance (VUS) in the cysteine-rich region of
      exon 10 in the RET gene (c.1846G>C, p.E616Q), in both affected siblings and their
      unaffected mother. Exon 10 RET mutations are known to be associated with HSCR and
      MEN2. Variants in the cysteine-rich region of the RET gene, outside of the key
      cysteine residues, may contribute to the development of MEN2 in a less aggressive
      manner, with a lower penetrance of MTC. Currently, a VUS in RET cannot be used to
      inform clinical management and direct future care. Analysis of RETE616Q reveals a
      gain of function mutant phenotype for this variant, which has not previously been
      reported, indicating that this VUS should be considered at risk for future
      clinical management.

PMID- 27704400
TI  - Certolizumab Pegol: A Review in Inflammatory Autoimmune Diseases.
AB  - Certolizumab pegol (Cimzia(r)) is a subcutaneously administered polyethylene
      glycolylated (PEGylated) antigen-binding fragment of a recombinant human
      monoclonal antibody that selectively neutralizes TNFalpha. The drug is indicated
      for a variety of inflammatory autoimmune diseases, including Crohn's disease
      (CD), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial
      spondyloarthritis (axSpA), based on its benefit in these settings in well
      designed clinical trials. In these studies, certolizumab pegol (as first- or
      subsequent-line therapy) reduced the severity of CD when used as an induction or
      maintenance therapy, and improved the signs/symptoms and slowed the radiographic
      progression of RA (with or without concomitant methotrexate), PsA and axSpA.
      Certolizumab pegol is generally well tolerated, with upper respiratory tract
      infections, rash and urinary tract infections being among the most frequent
      adverse reactions. Thus, certolizumab pegol is an effective option for the
      management of these autoimmune diseases.

PMID- 27704399
TI  - Consensus on the management of advanced radioactive iodine-refractory
      differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology
      Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group
      (GETHI).
AB  - Thyroid cancer is the single most prevalent endocrine malignancy; differentiated
      thyroid cancer (DTC) accounts for more than 90 % of all malignancies and its
      incidence has been rising steadily. For more patients, surgical treatment,
      radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH)
      suppressive therapy achieve an overall survival (OS) rate of 97.7 % at 5 years.
      Nevertheless, locoregional recurrence occurs in up to 20 % and distant metastases
      in approximately 10 % at 10 years. Two-thirds of these patients will never be
      cured with radioactive iodine therapy and will become RAI-refractory, with a 3
      year OS rate of less than 50 %. Over the last decade, substantial progress has
      been made in the management of RAI-refractory DTC. Given the controversy in some
      areas, the Spanish Task Force for Thyroid Cancer on behalf of Spanish Society of
      Endocrinology Thyroid Cancer Working Group (GTSEEN) and the Spanish Rare Cancer
      Working Group (GETHI) have created a national joint task force to reach a
      consensus addressing the most challenging aspects of management in these
      patients. In this way, multidisciplinary management should be mandatory and
      nuclear medicine targeted therapy, novel molecular targeted agents, and
      combinations are currently changing the natural history of RAI-refractory DTC.

PMID- 27704402
TI  - The effect of losartan therapy on ventricular function in Marfan patients with
      haploinsufficient or dominant negative FBN1 mutations.
AB  - BACKGROUND: Mild biventricular dysfunction is often present in patients with
      Marfan syndrome. Losartan has been shown to reduce aortic dilatation in patients
      with Marfan syndrome. This study assesses the effect of losartan on ventricular
      volume and function in genetically classified subgroups of asymptomatic Marfan
      patients without significant valvular regurgitation. METHODS: In this predefined
      substudy of the COMPARE study, Marfan patients were classified based on the
      effect of their FBN1 mutation on fibrillin-1 protein, categorised as
      haploinsufficient or dominant negative. Patients were randomised to a daily dose
      of losartan 100 mg or no additional treatment. Ventricular volumes and function
      were measured by magnetic resonance imaging at baseline and after 3 years of
      follow-up. RESULTS: Changes in biventricular dimensions were assessed in 163
      Marfan patients (48 % female; mean age 38 +/- 13 years). In patients with a
      haploinsufficient FBN1 mutation (n = 43), losartan therapy (n = 19) increased
      both biventricular end diastolic volume (EDV) and stroke volume (SV) when
      compared with no additional losartan (n = 24): left ventricular EDV: 9 +/- 26 ml
      vs. -8 +/- 24 ml, p = 0.035 and right ventricular EDV 12 +/- 23 ml vs. -18 +/- 24
      ml; p < 0.001 and for left ventricle SV: 6 +/- 16 ml vs. -8 +/- 17 ml; p = 0.009
      and right ventricle SV: 8 +/- 16 ml vs. -7 +/- 19 ml; p = 0.009, respectively. No
      effect was observed in patients with a dominant negative FBN1 mutation (n = 92),
      or without an FBN1 mutation (n = 28). CONCLUSION: Losartan therapy in
      haploinsufficient Marfan patients increases biventricular end diastolic volume
      and stroke volume, furthermore, losartan also appears to ameliorate biventricular
      filling properties.

PMID- 27704403
TI  - Grazing and abandonment determine different tree dynamics in wood-pastures.
AB  - Wood-pastures are threatened biotopes in which trees and livestock grazing
      maintain high conservation values. However, browsing may threaten tree
      regeneration, whereas abandonment leads to tree encroachment. We studied the
      regeneration of trees in a grazed and abandoned boreal wood-pastures. In grazed
      sites, the density of young spruces (Picea abies) was high, while the density of
      young birches (Betula spp.) was very low. Sprucification can be prevented only by
      removing spruces. The number of young birches and pines (Pinus sylvestris) was
      correlated with the number of junipers (Juniperus communis), probably because
      thorny junipers protect palatable seedlings from browsing. In abandoned sites,
      deciduous trees and spruces regenerated abundantly. In the long term, both
      grazing and abandonment lead to changes in tree species compositions and low
      diversity wood-pastures. Landscape scale planning and disturbance dynamics are
      needed for the creation of new wood-pastures and the maintenance of all pasture
      types within the landscape.

PMID- 27704404
TI  - Tablet Splitting of Antiepileptic Drugs in Pediatric Epilepsy: Potential Effect
      on Plasma Drug Concentrations.
AB  - INTRODUCTION: Tablet splitting is the process of dividing a tablet into portions
      to obtain a prescribed dose of medication. Very few studies have investigated
      whether split parts of a tablet deliver the expected amount of drug to patients.
      OBJECTIVE: Our objectives were to evaluate the split parts of adult-dose tablet
      formulations for percentage of weight deviation, weight uniformity, weight loss,
      drug content, and the content uniformity of four antiepileptic drugs (AEDs)
      prescribed to pediatric patients. We also measured AED plasma concentrations in
      the children. METHODS: We chose to study first-line AEDs (phenytoin sodium [PHE],
      sodium valproate [SVA], carbamazepine, and phenobarbitone) as they are routinely
      prescribed in India. We asked caregivers to perform the same splitting process
      they follow in their homes on three whole tablets during their routine visit to
      the outpatient department. After caregivers split the tablets, we studied the
      weight and content of the split parts. We also used high-performance liquid
      chromatography to study plasma drug concentrations in children who had received
      split AEDs for at least 4 months. RESULTS: A total of 168 caregivers participated
      in the study, and we analyzed 1098 split tablet parts. In total, 539 (49.0 %)
      split parts were above the specified limit of the 2010 Indian Pharmacopeia (IP)
      acceptable percentage weight deviation (PHE 169 [48.8 %], SVA 187 [51.9 %],
      carbamazepine 56 [41.1 %], phenobarbitone 127 [49.6 %]); 456 (41.5 %) split parts
      were outside the proxy IP specification for drug content (PHE 135 [39.0 %], SVA
      140 [38.8 %], carbamazepine 51 [37.5 %], phenobarbitone 130 [50.7 %]), and 253
      split parts were outside the acceptable content uniformity range of <85 % and
      >115 % (PHE 85 [24.5 %], SVA 98 [27.2 %], carbamazepine 14 [10.2 %],
      phenobarbitone 56 [21.8 %]). In total, 130 (72.2 %) patients had plasma drug
      concentrations outside the therapeutic range (PHE 36 [72.0 %], SVA 39 [78.0 %],
      carbamazepine 34 [68.0 %], phenobarbitone 21 [70.0 %]). CONCLUSIONS: Splitting
      adult-dosage formulations of AEDs results in patients not receiving the optimal
      dose. Plasma drug concentrations are also not optimal. Pediatric dosage
      formulations should be preferred to splitting adult-dosage formulations in
      pediatric epilepsy.

PMID- 27704405
TI  - The influence of interoceptive awareness on functional connectivity in patients
      with irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity
      likely related to altered processing of sensory stimuli along the brain-gut axis.
      Previous neuroimaging studies demonstrated structural and functional alteration
      of several brain areas involved in bodily representation, e.g. the insula, in
      patients with IBS. By means of resting-state functional magnetic resonance
      imaging (rs-fMRI) we searched for alteration of functional connectivity within
      the network involved in self-bodily consciousness. We found significant inverse
      correlation between hypochondriasis assessed through a clinical questionnaire and
      connectivity between posterior cingulate cortex and left supramarginal gyrus,
      extending into the adjacent superior temporal gyrus. Moreover, we observed a
      significant and positive correlation between a clinical questionnaire assessing
      interoception and connectivity between left anterior ventral insula and two
      clusters located in supramarginal gyrus bilaterally.Our findings highlight an
      "abnormal network synchrony" reflecting functional alteration, in the absence of
      structural and micro-structural changes, which might represent a possible
      therapeutic target for Irritable Bowel Syndrome.

PMID- 27704407
TI  - Subthalamic nucleus stimulation effects on single and combined task performance
      in Parkinson's disease patients: a PET study.
AB  - Subthalamic nucleus deep brain stimulation (STN-DBS) represents one of the most
      efficacious treatments for Parkinson's disease, along with L-dopa therapy. The
      objective of the present work was to identify the cerebral networks associated
      with hand movement and speech production tasks performed alone and
      simultaneously, as well as the effects of STN-DBS on these profiles. Clinical,
      behavioral, and neuroimaging (oxygen 15-labeled water and Positron Emission
      Tomography) investigations were used to study single and combined performances of
      unilateral hand movements and speech production in 11 unmedicated individuals
      with PD, both off and on STN-DBS. Specifically, a flexible factorial design with
      the tasks (hand movement, speech production, combined task) and the STN-DBS
      conditions (off, on) as main factors was chosen for brain activation statistical
      analysis, using a Family-Wise Error corrected p-value at the cluster level of at
      least 10 contiguous voxels. Increased activation of fronto-parietal and cingulate
      areas was observed under STN-DBS for hand movement in single and combined tasks,
      respectively, reflecting a partial restoration of cortico-sub-cortical
      connections. The lack of results for speech production for both off and on STN
      DBS could illustrate its relatively poor response to the treatment. STN-DBS
      tended to restore the additive function capacity that can be achieved when
      performing the combined task. We confirmed with original neuroimaging data that
      speech is much less responsive to STN-DBS than any other motor function and we
      concluded that speech outcomes following STN-DBS can be different from those
      observed pre-operatively following L-dopa administration.

PMID- 27704406
TI  - White matter abnormalities are associated with overall cognitive status in blast
      related mTBI.
AB  - Blast-related mild traumatic brain injury (mTBI) is a common injury of the Iraq
      and Afghanistan Wars. Research has suggested that blast-related mTBI is
      associated with chronic white matter abnormalities, which in turn are associated
      with impairment in neurocognitive function. However, findings are inconsistent as
      to which domains of cognition are affected by TBI-related white matter
      disruption. Recent evidence that white matter abnormalities associated with blast
      related mTBI are spatially variable raises the possibility that the associated
      cognitive impairment is also heterogeneous. Thus, the goals of this study were to
      examine (1) whether mTBI-related white matter abnormalities are associated with
      overall cognitive status and (2) whether white matter abnormalities provide a
      mechanism by which mTBI influences cognition. Ninety-six Operation Enduring
      Freedom/Operation Iraqi Freedom (OEF/OEF) veterans were assigned to one of three
      groups: no-TBI, mTBI without loss of consciousness (LOC) (mTBI-LOC), and mTBI
      with LOC (mTBI + LOC). Participants were given a battery of neuropsychological
      tests that were selected for their sensitivity to mTBI. Results showed that
      number of white matter abnormalities was associated with the odds of having
      clinically significant cognitive impairment. A mediation analysis revealed that
      mTBI + LOC was indirectly associated with cognitive impairment through its effect
      on white matter integrity. These results suggest that cognitive difficulties in
      blast-related mTBI can be linked to injury-induced neural changes when taking
      into account the variability of injury as well as the heterogeneity in cognitive
      deficits across individuals.

PMID- 27704409
TI  - Neural mapping of guilt: a quantitative meta-analysis of functional imaging
      studies.
AB  - Guilt is a self-conscious emotion associated with the negative appraisal of one's
      behavior. In recent years, several neuroimaging studies have investigated the
      neural correlates of guilt, but no meta-analyses have yet identified the most
      robust activation patterns. A systematic review of literature found 16 functional
      magnetic resonance imaging studies with whole-brain analyses meeting the
      inclusion criteria, for a total of 325 participants and 135 foci of activation. A
      meta-analysis was then conducted using activation likelihood estimation.
      Additionally, Meta-Analytic Connectivity Modeling (MACM) analysis was conducted
      to investigate the functional connectivity of significant clusters. The analysis
      revealed 12 significant clusters of brain activation (voxel-based FDR-corrected p
      < 0.05) located in the prefrontal, temporal and parietal regions, mainly in the
      left hemisphere. Only the left dorsal cingulate cluster survived stringent FWE
      correction (voxel-based p < 0.05). Secondary analyses (voxel-based FDR-corrected
      p < 0.05) on the 7 studies contrasting guilt with another emotional condition
      showed an association with clusters in the left precuneus, the anterior
      cingulate, the left medial frontal gyrus, the right superior frontal gyrus and
      the left superior temporal gyrus. MACM demonstrated that regions associated with
      guilt are highly interconnected. Our analysis identified a distributed neural
      network of left-lateralized regions associated with guilt. While voxel-based FDR
      corrected results should be considered exploratory, the dorsal cingulate was
      robustly associated with guilt. We speculate that this network integrates
      cognitive and emotional processes involved in the experience of guilt, including
      self-representation, theory of mind, conflict monitoring and moral values.
      Limitations of our meta-analyses comprise the small sample size and the
      heterogeneity of included studies, and concerns about naturalistic validity.

PMID- 27704408
TI  - Altered functional connectivity within and between the default model network and
      the visual network in primary open-angle glaucoma: a resting-state fMRI study.
AB  - To explore the alterations of functional connectivity (FC) and connections within
      and between the subnetworks of the visual network and the default mode network in
      glaucoma. We applied the independent component analysis to obtain two resting
      state networks (RSNs), which were the visual network and the default mode network
      (DMN), from the resting-state fMRI data of 25 primary open-angle glaucoma (POAG)
      patients and 25 well-matched normal controls. Then FC analysis was performed to
      obtain the altered FC within the RSNs, whereas the functional network
      connectivity (FNC) analysis was performed within and between these two RSNs. The
      abnormalities were correlated with clinical measures in glaucoma to investigate
      the abnormality-clinical relationship. FC analysis showed that the FC in the
      occipital pole of the visual network was decreased in POAG patients while no
      alterations were found in the FC of the DMN in patients. FNC analysis of
      connections within the RSNs found that two of the three connections within the
      visual network were decreased while no connection alterations were found within
      the DMN. FNC analysis of connections between these two RSNs found two increased
      connections and one decreased connection. The decreased connection between these
      two RSNs was positively correlated with the visual field mean deviation. These
      findings shed light on the importance of the reorganization of resting state
      networks in glaucoma mechanism, which may facilitate the understanding of
      glaucoma.

PMID- 27704411
TI  - ?

PMID- 27704412
TI  - ?

PMID- 27704410
TI  - Assessing the effects of cocaine dependence and pathological gambling using group
      wise sparse representation of natural stimulus FMRI data.
AB  - Assessing functional brain activation patterns in neuropsychiatric disorders such
      as cocaine dependence (CD) or pathological gambling (PG) under naturalistic
      stimuli has received rising interest in recent years. In this paper, we propose
      and apply a novel group-wise sparse representation framework to assess
      differences in neural responses to naturalistic stimuli across multiple groups of
      participants (healthy control, cocaine dependence, pathological gambling).
      Specifically, natural stimulus fMRI (N-fMRI) signals from all three groups of
      subjects are aggregated into a big data matrix, which is then decomposed into a
      common signal basis dictionary and associated weight coefficient matrices via an
      effective online dictionary learning and sparse coding method. The coefficient
      matrices associated with each common dictionary atom are statistically assessed
      for each group separately. With the inter-group comparisons based on the group
      wise correspondence established by the common dictionary, our experimental
      results demonstrated that the group-wise sparse coding and representation
      strategy can effectively and specifically detect brain networks/regions affected
      by different pathological conditions of the brain under naturalistic stimuli.

PMID- 27704414
TI  - ?

PMID- 27704413
TI  - ?

PMID- 27704415
TI  - ?

PMID- 27704416
TI  - ?

PMID- 27704417
TI  - ?

PMID- 27704418
TI  - ?

PMID- 27704419
TI  - [Epidemiology of hypertension: Prevalence, Awareness and Treatment].

PMID- 27704420
TI  - [Complications of minor operations in general practice].

PMID- 27704421
TI  - [The acute scrotum - primary diagnostic approach and treatment].

PMID- 27704422
TI  - [Emergency checklist - acute urinary retention].

PMID- 27704424
TI  - [Management of acute renal colic in the ambulatory care setting].

PMID- 27704423
TI  - [Acute pyelonephritis].

PMID- 27704425
TI  - ?

PMID- 27704426
TI  - ?

PMID- 27704427
TI  - ?

PMID- 27704428
TI  - ?

PMID- 27704430
TI  - ?

PMID- 27704429
TI  - ?

PMID- 27704431
TI  - ?

PMID- 27704432
TI  - ?

PMID- 27704433
TI  - ?

PMID- 27704434
TI  - ?

PMID- 27704435
TI  - ?

PMID- 27704436
TI  - ?

PMID- 27704437
TI  - ?

PMID- 27704438
TI  - ?

PMID- 27704440
TI  - ?

PMID- 27704439
TI  - ?

PMID- 27704441
TI  - ?

PMID- 27704442
TI  - ?

PMID- 27704443
TI  - ?

PMID- 27704444
TI  - ?

PMID- 27704445
TI  - ?

PMID- 27704446
TI  - ?

PMID- 27704447
TI  - ?

PMID- 27704448
TI  - ?

PMID- 27704449
TI  - ?

PMID- 27704450
TI  - ?

PMID- 27704451
TI  - ?

PMID- 27704452
TI  - ?

PMID- 27704454
TI  - ?

PMID- 27704455
TI  - [Visual diagnoses - what you can read in the face of your patients].

PMID- 27704456
TI  - A Provably-Secure Transmission Scheme for Wireless Body Area Networks.
AB  - Wireless body area network (WBANs) is composed of sensors that collect and
      transmit a person's physiological data to health-care providers in real-time. In
      order to guarantee security of this data over open networks, a secure data
      transmission mechanism between WBAN and application provider's servers is of
      necessity. Modified medical data does not provide a true reflection of an
      individuals state of health and its subsequent use for diagnosis could lead to an
      irreversible medical condition. In this paper, we propose a lightweight
      certificateless signcryption scheme for secure transmission of data between WBAN
      and servers. Our proposed scheme not only provides confidentiality of data and
      authentication in a single logical step, it is lightweight and resistant to key
      escrow attacks. We further provide security proof that our scheme provides
      indistinguishability against adaptive chosen ciphertext attack and unforgeability
      against adaptive chosen message attack in random oracle model. Compared with two
      other Diffie-Hellman based signcryption schemes proposed by Barbosa and Farshim
      (BF) and another by Yin and Liang (YL), our scheme consumes 46 % and 8 % less
      energy during signcryption than BF and YL scheme respectively.

PMID- 27704457
TI  - Opportunities and Accountable Care Organizations.

PMID- 27704458
TI  - IFCM Based Segmentation Method for Liver Ultrasound Images.
AB  - In this paper we have proposed an iterative Fuzzy C-Mean (IFCM) method which
      divides the pixels present in the image into a set of clusters. This set of
      clusters is then used to segment a focal liver lesion from a liver ultrasound
      image. Advantage of IFCM methods is that n-clusters FCM method may lead to non
      uniform distribution of centroids, whereas in IFCM method centroids will always
      be uniformly distributed. Proposed method is compared with the edge based Active
      contour Chan-Vese (CV) method, and MAP-MRF method by implementing the methods on
      MATLAB. Proposed method is also compared with region based active contour region
      scalable fitting energy (RSFE) method whose MATLAB code is available in author's
      website. Since no comparison is available on a common database, the performance
      of three methods and the proposed method have been compared on liver ultrasound
      (US) images available with us. Proposed method gives the best accuracy of 99.8 %
      as compared to accuracy of 99.46 %, 95.81 % and 90.08 % given by CV, MAP-MRF and
      RSFE methods respectively. Computation time taken by the proposed segmentation
      method for segmentation is 14.25 s as compared to 44.71, 41.27 and 49.02 s taken
      by CV, MAP-MRF and RSFE methods respectively.

PMID- 27704459
TI  - Enhancement of Structured Reporting - an Integration Reporting Module with
      Radiation Dose Collection Supporting.
AB  - Collection of radiation dose derived from radiological examination is necessary
      not only for radiation protection, but also for fulfillment of structured
      reports. However, the material regarding of radiation dose cannot be directly
      utilized by the Radiological Information System (RIS) since it is generated and
      only stored in the Picture Archiving and Communication System (PACS). In this
      paper, an integration reporting module is proposed to facilitate handling of dose
      information and structured reporting by providing two functionalities. First, a
      gateway is established to automatically collect the related information from PACS
      for further analyzing and monitoring the accumulated radiation. Second, the
      designated structured reporting patterns with corresponding radiation dose
      measurements can be acquired by radiologists as necessary. In the design, the
      radiation dose collection gateway and the well-established pattern are collocated
      to achieve that there is no need to do manual entry for structured reporting,
      thus increasing productivity and medical quality.

PMID- 27704460
TI  - Advances in Green Organic Sonochemistry.
AB  - Over the past 15 years, sustainable chemistry has emerged as a new paradigm in
      the development of chemistry. In the field of organic synthesis, green chemistry
      rhymes with relevant choice of starting materials, atom economy, methodologies
      that minimize the number of chemical steps, appropriate use of benign solvents
      and reagents, efficient strategies for product isolation and purification and
      energy minimization. In that context, unconventional methods, and especially
      ultrasound, can be a fine addition towards achieving these green requirements.
      Undoubtedly, sonochemistry is considered as being one of the most promising green
      chemical methods (Cravotto et al. Catal Commun 63: 2-9, 2015). This review is
      devoted to the most striking results obtained in green organic sonochemistry
      between 2006 and 2016. Furthermore, among catalytic transformations, oxidation
      reactions are the most polluting reactions in the chemical industry; thus, we
      have focused a part of our review on the very promising catalytic activity of
      ultrasound for oxidative purposes.

PMID- 27704462
TI  - Genome-wide scan in two groups of HIV-infected patients treated with dendritic
      cell-based immunotherapy.
AB  - We performed a retrospective genome-wide association study in HIV-infected
      individuals who were treated with dendritic cell-based immunotherapy in clinical
      trials performed by two research groups (Spain and Brazil). We aimed to identify
      host genetic variants influencing treatment response. The Illumina Human Core
      Exome 12 v 1.0 Bead Chip with over 250,000 markers was used to analyze genetic
      factors affecting treatment response. Additionally, we performed a meta-analysis
      of the results obtained from Spanish and Brazilian patients. We identified a
      genetic variation (rs7935564 G allele) in TRIM22 gene, which encodes TRIM22
      protein acting like a HIV restriction factor, as being associated with good
      response to dendritic cell-based immunotherapy. We then verified the impact of
      TRIM22 rs7935564 SNP in susceptibility to HIV infection and disease progression
      by assessing the influence of biogeographic ancestry in the distribution of
      allelic and genotype frequencies in three populations from Italy, Brazil and
      Zambia. TRIM22 rs7935564 genotyping indicated association of G rs7935564 allele
      with long-term non-progression of HIV disease in Italian patients, thus
      corroborating our hypothesis that it is involved as a restriction factor in
      dendritic cell-based immunotherapy response. TRIM22 rs7935564 polymorphism was
      associated with good response to dendritic cell-based immunotherapy. We
      hypothesize that in selecting patients for treatment, there is a possible bias
      related to the natural presence of restriction factors that are genetically
      determined and could influence final outcome of therapy.

PMID- 27704463
TI  - 2-Deoxy glucose regulate MMP-9 in a SIRT-1 dependent and NFkB independent
      mechanism.
AB  - MMP9 is a member of the family of zinc-containing endopeptidases which degrade
      various components of the extracellular matrix, thereby regulating matrix
      remodeling. Since matrix remodeling plays an important role during growth and
      progression of cancer and considering the fact that, tumor cells switch to
      aerobic glycolysis as its major energy source, this study was designed to analyze
      if partial inhibition of glycolysis (the major energy pathway during hypoxia) can
      be used as a means to control matrix remodeling in terms of MMP9 activity and
      expression. For this, human epithelial carcinoma cells were treated with
      glycolytic inhibitor, 2-deoxy glucose (2DG) at sub-lethal concentrations followed
      by analysis of the expression and activity of MMP2 and MMP9. The experimental
      findings demonstrate that exposure of cancer cells to glycolytic inhibitor at
      concentration that does not induce ER stress, downregulates the activity and
      expression of MMP9 without affecting the expression levels and activity of MMP2.
      Further mechanistic analysis revealed that the regulation of MMP9 was mediated in
      a SIRT-1 dependent mechanism and did not alter the NFkB signaling pathway. The
      overall results presented here, therefore suggest that the use of glycolytic
      inhibitor, 2DG at concentration that do not affect cell viability or induce ER
      stress can be an effective strategy to control matrix remodeling.

PMID- 27704464
TI  - GL-9 peptide regulates gene expression of CD44 cancer marker and pro-inflammatory
      cytokine TNF-alpha in human lung epithelial adenocarcinoma cell line (A549).
AB  - In this study, we examined cytotoxic effect of GL-9 peptide on A459 cell line
      through studying the changes in TNF-alpha and CD44 gene expression and ROS
      production. Real-time PCR analysis showed that the treated A549 cells highly over
      expressed TNF-alpha, which was associated with a significant reduction of CD44
      gene expression levels (p  <  0.05). ROS production rate was measured through the
      usage of DCFH-DA primer. Results demonstrated that GL-9 peptide could also induce
      cell death via ROS production. The effect of GL-9 peptide on human erythrocytes
      and leukocytes was analyzed. GL-9 peptide showed no significant toxic effect on
      human blood cells. Our results suggested that the GL-9 peptide as a potent
      natural agent could modulate gene expression of cancer cell markers.

PMID- 27704465
TI  - Lymphocyte genotoxicity and protective effect of Calyptranthes tricona
      (Myrtaceae) against H2O2-induced cell death in MCF-7 cells.
AB  - Calyptranthes tricona is a species (Myrtaceae) native to South Brazil. Plants
      belonging to this family are folkloric used for analgesia, inflammation, and
      infectious diseases. However, little is known about the toxic potential of C.
      tricona. The present study aimed to evaluate the antioxidant activity of C.
      tricona ethanol and hexane leaf extracts, as well as verify their effect on human
      lymphocytes and MCF-7 cells. The extracts were subjected to preliminary
      phytochemical screening, antioxidant activity using DPPH and ORAC methods.
      Genotoxic and mutagenic effects in cultured human lymphocytes were assessed using
      the comet assay and the micronucleus assay, respectively. In addition, cell
      viability by MTT assay and fluorometric analysis of mitochondrial potential and
      caspases-9 activity were performed in order to verify the possible effects of
      both extracts on H2O2-induced cell death of MCF-7 cells. Our findings revealed
      that the phenol content and the antioxidant activity were only present in the
      ethanol extract. Also, the phytochemical screening presented steroids,
      triterpenoids, condensed tannins, and flavones as the main compounds. However,
      both extracts were capable of inducing concentration-dependent DNA damage in
      human lymphocytes. When treating MCF-7 cells with the extracts, both of them
      inhibited MCF-7 cell death in response to oxidative stress through a decrease of
      mitochondrial depolarization and caspases-9 activity. Thus, our results need to
      be considered in future in vitro and in vivo studies of C. tricona effects. In
      the meanwhile, we recommend caution in the acute/chronic use of this homemade
      preparation for medicinal purpose.

PMID- 27704466
TI  - Anti-arthritogenic and cardioprotective action of hesperidin and daidzein in
      collagen-induced rheumatoid arthritis.
AB  - Atherosclerosis has been linked to chronic inflammatory processes. Changes in the
      levels of lipoproteins, especially low-density lipoprotein or its variants, as
      well as inflammatory markers are risk factors for the atherosclerosis. In the
      present study, an experimental model of rheumatoid arthritis was developed by
      administrating collagen suspension intradermally in the tail region of Wistar
      albino rats. At the same time, a suspension of hesperidin (50 mg/kg body weight)
      and daidzein (20 mg/kg body weight) was orally administrated. The compounds were
      given in the morning and evening for 21 days. Levels of inflammatory markers in
      the homogenate of knee joints of experimental rats as well as plasma lipoproteins
      were investigated. The administration of hesperidin and daidzein caused
      significant (p < 0.001) decrease in articular elastase activity, TNF-alpha, and
      malondialdehyde levels. Further, arthritis scoring and histological findings
      supported the anti-inflammatory actions of the test compounds. Interestingly, the
      test compounds also lowered the plasma low-density lipoprotein cholesterol, very
      low-density lipoprotein cholesterol, and triglyceride but increased the level of
      high-density lipoprotein cholesterol. The test compounds thus ameliorated the
      risk factors of atherosclerosis. Furthermore, antioxidant roles of hesperidin as
      well as daidzein were evident from decrease in free radical load demonstrated as
      increase in total antioxidant level in plasma of arthritic animals treated with
      hesperidin and daidzein. In a separate in vitro experiment, enhanced free radical
      scavenging activity of hesperidin was demonstrated against 2,2-diphenyl-1
      picrylhydrazyl and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid. The anti
      inflammatory, hypolipidemic, and antioxidant actions of the naturally occurring
      test compounds, particularly hesperidin, seem to be quite effective against
      rheumatoid arthritis and atherosclerosis. Thus, their consumption may be helpful
      in prevention or at least delaying the onset of these diseases in susceptible
      individuals.

PMID- 27704467
TI  - Palliative and End-of-Life Care in Myelodysplastic Syndromes.
AB  - A growing literature demonstrates that MDS is associated with significant
      impairments in overall quality of life. Given the poor prognosis for many
      patients with MDS, and the considerable morbidities associated with this disease,
      there is a critical need to address palliative and end-of-life care needs in this
      population. However, palliative and end-of-life care issues are under-represented
      in the MDS literature. In this article, we highlight a growing body of literature
      that demonstrates unmet palliative and end-of-life care needs in hematologic
      malignancies, including MDS, and highlight opportunities for further research and
      quality improvement initiatives to address unmet needs in MDS care.

PMID- 27704469
TI  - Growth and yield performance of Pleurotus ostreatus (Jacq. Fr.) Kumm (oyster
      mushroom) on different substrates.
AB  - Mushroom cultivation is reported as an economically viable bio-technology process
      for conversion of various lignocellulosic wastes. Given the lack of technology
      know-how on the cultivation of mushroom, this study was conducted in Wondo Genet
      College of Forestry and Natural Resource, with the aim to assess the suitability
      of selected substrates (agricultural and/or forest wastes) for oyster mushroom
      cultivation. Accordingly, four substrates (cotton seed, paper waste, wheat straw,
      and sawdust) were tested for their efficacy in oyster mushroom production. Pure
      culture of oyster mushroom was obtained from Mycology laboratory, Department of
      Plant Biology and Biodiversity Management, Addis Ababa University. The pure
      culture was inoculated on potato dextrose agar for spawn preparation. Then, the
      spawn containing sorghum was inoculated with the fungal culture for the formation
      of fruiting bodies on the agricultural wastes. The oyster mushroom cultivation
      was undertaken under aseptic conditions, and the growth and development of
      mushroom were monitored daily. Results of the study revealed that oyster mushroom
      can grow on cotton seed, paper waste, sawdust and wheat straw, with varying
      growth performances. The highest biological and economic yield, as well as the
      highest percentage of biological efficiency of oyster mushroom was obtained from
      cotton seed, while the least was from sawdust. The study recommends cotton seed,
      followed by paper waste as suitable substrates for the cultivation of oyster
      mushroom. It also suggests that there is a need for further investigation on
      various aspects of oyster mushroom cultivation in Ethiopia to promote the
      industry.

PMID- 27704470
TI  - Recovery of platinum(0) through the reduction of platinum ions by hydrogenase
      displaying yeast.
AB  - Biological technologies for recycling rare metals, which are essential for high
      tech products, have attracted much attention because they could prove to be more
      environmentally friendly and energy-saving than other methods. We have developed
      biological recycling technologies by cell surface engineering for the selective
      recovery of toxic heavy metal ions and rare metal ions from aqueous wastes. In
      this study, we aimed to construct a unique biological technique to recover rare
      metals 'in solid' form by reducing rare metal ions, leading to a practical next
      generation recovery system. Sulfate-reducing bacteria (SRB) can reduce Pt(II) to
      Pt(0), and hydrogenases of SRB contribute to the reduction. Therefore, we
      constructed yeasts displaying their hydrogenases on the 'cell membrane', and
      reduction experiments were performed under anaerobic conditions without any
      electron donors. As a result, hydrogenase-displaying yeasts produced black
      precipitates in PtCl42- solution. Based on X-ray photoelectron spectroscopy (XPS)
      and transmission electron microscopy (TEM) observations, the constructed yeasts
      were found to successfully produce the precipitates of Pt(0) through the
      reduction of Pt(II). Interestingly, the precipitates of Pt(0) were formed as
      nanoparticles, suitable for industrial usage.

PMID- 27704471
TI  - Expression, purification and immobilization of tannase from Staphylococcus
      lugdunensis MTCC 3614.
AB  - Enzymes find their applications in various industries, due to their error free
      conversion of substrate into product. Tannase is an enzyme used by various
      industries for degradation of tannin. Biochemical characterization of a specific
      enzyme from one organism to other is one of the ways to search for enzymes with
      better traits for industrial applications. Here, tannase encoding gene from
      Staphylococcus lugdunensis was cloned and suitability of the enzyme in various
      conditions was analysed to find its application in various industry. The
      recombinant protein was expressed with 6* His tag and purified using nickel
      affinity beads. The enzyme was purified up to homogeneity, with approximate
      molecular weight of 66 kDa. Purified tannase exhibited specific activity of about
      716 U/mg. Optimum enzyme activity was found to be 40  degrees C at pH 7.0.
      Biochemical characterization revealed; metal ions such as Zn2+, Fe2+, Fe3+ and
      Mn2+ inhibited tannase activity, and SDS at lower concentration, increased
      tannase activity. Non polar organic solvents increased the tannase activity and
      polar solvents inhibited the tannase activity. Tannase immobilization studies
      show protection of the enzyme under wide range of pH and temperature. Also in
      this study we report a method for recovery and repeated use of the tannase.

PMID- 27704468
TI  - Sezary Syndrome: Clinical and Biological Aspects.
AB  - Sezary syndrome (SS) is a rare and aggressive type of cutaneous T cell lymphoma
      (CTCL) characterized by an intensely pruritic, exfoliative rash, known as
      erythroderma, with cutaneous and systemic dissemination of clonal CD4+ T cells
      into the blood and lymph nodes. This review aims to present recent advancements
      in the biological and clinical aspects of SS. We begin by providing an overview
      of the diagnostic criteria for SS and reviewing some of its epidemiological and
      clinical aspects. We then discuss updates in the etiology of this elusive disease
      and the genetic and molecular landscapes that define it. Finally, we provide a
      short overview of the current therapeutic strategies for SS as well as recent
      advances in the prognosis of this disease. A brief set of recommendations is
      provided regarding future directions in research and therapy.

PMID- 27704472
TI  - [Revival after Ebola: multidisciplinary assessment at 1 year, prospect and follow
      up study of surviving patients from Ebola in Guinea (PostEboGui cohort)].
AB  - Ebola virus disease (EVD) epidemic that spread in West Africa from the end of
      2013 to early 2016 has reached more people than all past epidemics. Beyond care
      management of acute phase ill patients and measures for the control of the
      epidemic, the outcome of Ebola survivors became an important question as their
      number increased and raised new issues. A multidisciplinary prospective cohort of
      survivors in Guinea has been launched by IRD UMI 233 and Donka National Hospital,
      Conakry, Guinea, to assess the long-term clinical, psychological, sociological,
      immunological, and viral outcomes potentially related to EVD. This paper
      describes PostEboGui Programme, constraints and changes to the initial proposal,
      participants, first results, and new issues, 1 year after its start, in a
      descriptive and critical view. We started also to work on ethical aspects in the
      context of epidemics and of mass interventions with a risk of overinvestigation
      of patients.

PMID- 27704473
TI  - Direct Visualization of Neurotransmitters in Rat Brain Slices by Desorption
      Electrospray Ionization Mass Spectrometry Imaging (DESI - MS).
AB  - Mass spectrometry imaging (MSI) of neurotransmitters has so far been mainly
      performed by matrix-assisted laser desorption/ionization (MALDI) where
      derivatization reagents, deuterated matrix and/or high resolution, or tandem MS
      have been applied to circumvent problems with interfering ion peaks from matrix
      and from isobaric species. We herein describe the application of desorption
      electrospray ionization mass spectrometry imaging (DESI)-MSI in rat brain coronal
      and sagittal slices for direct spatial monitoring of neurotransmitters and
      choline with no need of derivatization reagents and/or deuterated materials. The
      amino acids gamma-aminobutyric (GABA), glutamate, aspartate, serine, as well as
      acetylcholine, dopamine, and choline were successfully imaged using a commercial
      DESI source coupled to a hybrid quadrupole-Orbitrap mass spectrometer. The
      spatial distribution of the analyzed compounds in different brain regions was
      determined. We conclude that the ambient matrix-free DESI-MSI is suitable for
      neurotransmitter imaging and could be applied in studies that involve evaluation
      of imbalances in neurotransmitters levels. Graphical Abstract ?.

PMID- 27704474
TI  - Separation of cis and trans Isomers of Polyproline by FAIMS Mass Spectrometry.
AB  - High field asymmetric waveform ion mobility spectrometry (FAIMS) is well
      established as a tool for separating peptide isomers (sequence inversions and
      post-translationally modified localization variants). Here, we demonstrate the
      FAIMS is able to differentiate cis and trans isomers of polyproline. Polyproline
      assumes an all-cis conformation-the PPI helix-in 1-propanol, and an all-trans
      conformation-the PPII helix-in aqueous solutions. Differentiation of these
      conformers may be achieved both through use of a cylindrical FAIMS device and a
      miniaturized ultrahigh field planar FAIMS device. Graphical Abstract ?.

PMID- 27704475
TI  - Expression and Enzyme Activity Detection of a Sepiapterin Reductase Gene from
      Musca domestica Larva.
AB  - Tetrahydrobiopterin (BH4) is an essential cofactor for aromatic acid hydroxylases
      and nitric oxide synthase. Sepiapterin reductase (SPR) catalyzes the final steps
      of BH4 biosynthesis. Studies on SPR from several insects and other organisms have
      been reported. However, thus far, enzyme activity of SPR in Musca domestica is
      kept unknown. In this study, 186 differentially expressed genes including SPR
      gene from Musca domestica (MDSPR) were screened in subtractive cDNA library. The
      MDSPR gene was cloned, and the recombinant MDSPI16 protein was expressed as a 51
      kDa protein in soluble form. The MDSPR exhibited strong activity to the substrate
      sepiapterin (SP). The values of Vmax and Km of the MDSPR for SP were 6.83 MUM/min
      and 23.48 MUM, and the optimum temperature and pH of MDSPR were 50  degrees C and
      4.0, respectively. This study provides new hypotheses and methods for the
      production of BH4 using insect-derived SPR.

PMID- 27704476
TI  - Simultaneous Production of Amyloglucosidase and Exo-Polygalacturonase by
      Aspergillus niger in a Rotating Drum Reactor.
AB  - Simultaneous production of amyloglucosidase (AMG) and exo-polygalacturonase (exo
      PG) was carried out by Aspergillus niger in substrate of defatted rice bran in a
      rotating drum bioreactor (RDB) and studied by a 31 * 22 factorial experimental
      design. Variables under study were A. niger strains (A. niger NRRL 3122 and A.
      niger t0005/007-2), types of inoculum (spore suspension and fermented bran), and
      types of inducer (starch, pectin, and a mix of both). Solid-state fermentation
      process (SSF) was conducted at 30  degrees C under 60-vvm aeration for 96 h in a
      pilot scale. Production of AMG and exo-PG was significantly affected by the
      fungal strain and the type of inoculum, but inducers did not trigger any
      significant effect, an evidence of the fact that these enzymes are constitutive.
      The maximum activity of exo-PG was 84 U gdm-1 whereas the maximum yield of AMG
      was 886.25 U gdm-1.

PMID- 27704477
TI  - Physical and Covalent Immobilization of Lipase onto Amine Groups Bearing Thiol
      Ene Photocured Coatings.
AB  - In this study, amine groups containing thiol-ene photocurable coating material
      for lipase immobilization were prepared. Lipase (EC 3.1.1.3) from Candida rugosa
      was immobilized onto the photocured coatings by physical adsorption and
      glutaraldehyde-activated covalent bonding methods, respectively. The catalytic
      efficiency of the immobilized and free enzymes was determined for the hydrolysis
      of p-nitrophenyl palmitate and also for the synthesis of p-nitrophenyl linoleate.
      The storage stability and the reusability of the immobilized enzyme and the
      effect of temperature and pH on the catalytic activities were also investigated.
      The optimum pH for free lipase and physically immobilized lipase was determined
      as 7.0, while it was found as 7.5 for the covalent immobilization. After
      immobilization, the optimum temperature increased from 37  degrees C (free
      lipase) to 50-55  degrees C. In the end of 15 repeated cycles, covalently bounded
      enzyme retained 60 and 70 % of its initial activities for hydrolytic and
      synthetic assays, respectively. While the physically bounded enzyme retained only
      56 % of its hydrolytic activity and 67 % of its synthetic activity in the same
      cycle period. In the case of hydrolysis V max values slightly decreased after
      immobilization. For synthetic assay, the V max value for the covalently
      immobilized lipase was found as same as free lipase while it decreased
      dramatically for the physically immobilized lipase. Physically immobilized enzyme
      was found to be superior over covalent bonding in terms of enzyme loading
      capacity and optimum temperature and exhibited comparable re-use values and
      storage stability. Thus, a fast, easy, and less laborious method for lipase
      immobilization was developed.

PMID- 27704478
TI  - Cushing's syndrome and pregnancy outcomes: a systematic review of published
      cases.
AB  - Pregnancy in Cushing's syndrome (CS) is extremely rare due to the influence of
      hypercortisolism on the reproductive axis. Purpose of this study is to
      investigate whether the etiology of CS in pregnancy determines a different impact
      on the fetal/newborn and maternal outcomes. We performed a systematic review of
      cases published in the literature from January 1952 to April 2015 including the
      words "Cushing AND pregnancy". We included 168 manuscripts containing 220
      patients and 263 pregnancies with active CS during pregnancy and with a history
      of CS but treated and cured hypercortisolism at the time of gestation. Adrenal
      adenoma was the main cause of active CS during pregnancy (44.1 %). Women with
      active CS had more gestational diabetes mellitus (36.9 vs. 2.3 %, p = 0.003),
      gestational hypertension (40.5 vs. 2.3 %, p < 0.001) and preeclampsia (26.3 vs.
      2.3 %, p = 0.001) than those with cured disease. The proportion of fetal loss in
      active CS was higher than in cured CS (23.6 vs. 8.5 %, p = 0.021), as well as
      global fetal morbidity (33.3 vs. 4.9 %, p < 0.001). The predictors of fetal loss
      in active CS were etiology of hypercortisolism [Odds Ratio -OR-for pregnancy
      induced CS 4.7 (95 % Confidence Interval-CI 1.16-18.96), p = 0.03], publication
      period [OR for "1975-1994" 0.10 (95 % CI 0.03-0.40), p = 0.001] and treatment
      during gestation (p = 0.037, [OR medical treatment 0.25 (95 % CI 0.06-1.02), p =
      0.052], [OR surgical treatment 0.34 (95 % CI 0.11-1.06), p = 0.063]). The period
      of diagnosis of CS (before, during or after pregnancy) was the only predictor of
      overall fetal morbimortality [OR for diagnosis during pregnancy 4.66 (95 % CI
      1.37-15.83), p = 0.014]. Patients with active CS, especially in pregnancy-induced
      CS, experienced more problems in pregnancy and had the worst fetal prognosis in
      comparison to other causes. Diagnosis of CS during pregnancy was also associated
      with worse overall fetal morbimortality. Both medical treatment and surgery
      during pregnancy appeared to be protective in avoiding fetal loss.

PMID- 27704479
TI  - Estrogens and selective estrogen receptor modulators in acromegaly.
AB  - Despite recent advances in acromegaly treatment by surgery, drugs, and
      radiotherapy, hormonal control is still not achieved by some patients. The
      impairment of IGF-1 generation by estrogens in growth hormone deficient patients
      is well known. Patients on oral estrogens need higher growth hormone doses in
      order to achieve normal IGF-1 values. In the past, estrogens were one of the
      first drugs used to treat acromegaly. Nevertheless, due to the high doses used
      and the obvious side effects in male patients, this strategy was sidelined with
      the development of more specific drugs, as somatostatin receptor ligands and
      dopamine agonists. In the last 15 years, the antagonist of growth hormone
      receptor became available, making possible IGF-1 control of the majority of
      patients on this particular drug. However, due to its high cost, pegvisomant is
      still not available in many centers around the world. In this setting, the effect
      of estrogens and also of selective estrogen receptor modulators on IGF-1 control
      was reviewed, and proved to be an ancillary tool in the management of acromegaly.
      This review describes data concerning their efficacy and place in the treatment
      algorithm of acromegaly.

PMID- 27704480
TI  - Long-term outcome of multimodal therapy for giant prolactinomas.
AB  - Giant prolactinomas are rare tumors characterized by their large size,
      compressive symptoms, and extremely high prolactin secretion. The aim of this
      study is to describe our experience with a series of 16 giant prolactinomas cases
      in terms of clinical presentation, therapeutic decisions, and final outcomes.
      Retrospective analysis of adult patients diagnosed with giant prolactinomas at
      the endocrine departments of three university tertiary hospitals. We included 16
      patients (43.7 % women); mean age at diagnosis: 42.1 +/- 21 years. The most
      frequent presentation was compressive symptoms. The delay in diagnosis was higher
      in women (median of 150 months vs. 12 in men; p = 0.09). The mean maximum tumor
      diameter at diagnosis was 56.9 +/- 15.5 mm, and mean prolactin levels were
      10,995.9 +/- 12,157.8 ng/mL. Dopamine agonists were the first-line treatment in
      11 patients (mean maximum dose: 3.9 +/- 3.2 mg/week). Surgery was the initial
      treatment in five patients and the second-line treatment in six. Radiotherapy was
      used in four cases. All patients but one, are still with dopamine agonists. After
      a mean follow-up of 9 years, prolactin normalized in 7/16 patients (43.7 %) and
      13 patients (81 %) reached prolactin levels lower than twice the upper limit of
      normal. Mean prolactin level at last visit: 79.5 +/- 143 ng/mL. Tumor volume was
      decreased by 93.8 +/- 11.3 %, and final maximum tumor diameter was 18.4 +/- 18.8
      mm. Three patients are actually tumor free. Giant prolactinomas are characterized
      by a large tumor volume and extreme prolactin hypersecretion. Multimodal
      treatment is frequently required to obtain biochemical and tumor control.

PMID- 27704481
TI  - Heparin-binding protein is important for vascular leak in sepsis.
AB  - BACKGROUND: Elevated plasma levels of heparin-binding protein (HBP) are
      associated with risk of organ dysfunction and mortality in sepsis, but little is
      known about causality and mechanisms of action of HBP. The objective of the
      present study was to test the hypothesis that HBP is a key mediator of the
      increased endothelial permeability observed in sepsis and to test potential
      treatments that inhibit HBP-induced increases in permeability. METHODS:
      Association between HBP at admission with clinical signs of increased
      permeability was investigated in 341 patients with septic shock. Mechanisms of
      action and potential treatment strategies were investigated in cultured human
      endothelial cells and in mice. RESULTS: Following adjustment for comorbidities
      and Acute Physiology and Chronic Health Evaluation (APACHE) II, plasma HBP
      concentrations were weakly associated with fluid overload during the first 4 days
      of septic shock and the degree of hypoxemia (PaO2/FiO2) as measures of increased
      systemic and lung permeability, respectively. In mice, intravenous injection of
      recombinant human HBP induced a lung injury similar to that observed after
      lipopolysaccharide injection. HBP increased permeability of vascular endothelial
      cell monolayers in vitro, and enzymatic removal of luminal cell surface
      glycosaminoglycans (GAGs) using heparinase III and chondroitinase ABC abolished
      this effect. Similarly, unfractionated heparins and low molecular weight heparins
      counteracted permeability increased by HBP in vitro. Intracellular, selective
      inhibition of protein kinase C (PKC) and Rho-kinase pathways reversed HBP
      mediated permeability effects. CONCLUSIONS: HBP is a potential mediator of sepsis
      induced acute lung injury through enhanced endothelial permeability. HBP
      increases permeability through an interaction with luminal GAGs and activation of
      the PKC and Rho-kinase pathways. Heparins are potential inhibitors of HBP-induced
      increases in permeability.

PMID- 27704482
TI  - Molecular Breeding of Rice Restorer Lines and Hybrids for Brown Planthopper (BPH)
      Resistance Using the Bph14 and Bph15 Genes.
AB  - BACKGROUND: The development of hybrid rice is a practical approach for increasing
      rice production. However, the brown planthopper (BPH), Nilaparvata lugens Stal,
      causes severe yield loss of rice (Oryza sativa L.) and can threaten food
      security. Therefore, breeding hybrid rice resistant to BPH is the most effective
      and economical strategy to maintain high and stable production. Fortunately,
      numerous BPH resistance genes have been identified, and abundant linkage markers
      are available for molecular marker-assisted selection (MAS) in breeding programs.
      Hence, we pyramided two BPH resistance genes, Bph14 and Bph15, into a susceptive
      CMS restorer line Huahui938 and its derived hybrids using MAS to improve the BPH
      resistance of hybrid rice. RESULTS: Three near-isogenic lines (NILs) with
      pyramided Bph14 and Bph15 were obtained by molecular marker-assisted backcross
      (MAB) and phenotypic selection. The genomic components of these NILs were
      detected using the whole-genome SNP (Single nucleotide polymorphism) array,
      RICE6K, suggesting that the recurrent parent genome (RPG) recovery of the NILs
      was 87.88, 87.70 and 86.62 %, respectively. BPH bioassays showed that the
      improved NILs and their derived hybrids carrying homozygous Bph14 and Bph15 were
      resistant to BPH. However, the hybrids with heterozygous Bph14 and Bph15 remained
      susceptible to BPH. The developed NILs showed no significant differences in major
      agronomic traits and rice qualities compared with the recurrent parent. Moreover,
      the improved hybrids derived from the NILs exhibited better agronomic performance
      and rice quality compared with the controls under natural field conditions.
      CONCLUSIONS: This study demonstrates that it is essential to stack Bph14 and
      Bph15 into both the maternal and paternal parents for developing BPH-resistant
      hybrid rice varieties. The SNP array with abundant DNA markers is an efficient
      tool for analyzing the RPG recovery of progenies and can be used to monitor the
      donor segments in NILs, thus being extremely important for rice molecular
      breeding.

PMID- 27704483
TI  - Slackline Training (Balancing Over Narrow Nylon Ribbons) and Balance Performance:
      A Meta-Analytical Review.
AB  - BACKGROUND: Adequate static and dynamic balance performance is an important
      prerequisite during daily and sporting life. Various traditional and innovative
      balance training concepts have been suggested to improve postural control or
      neuromuscular fall risk profiles over recent years. Whether slackline training
      (balancing over narrow nylon ribbons) serves as an appropriate training strategy
      to improve static and dynamic balance performance is as yet unclear. OBJECTIVE:
      The aim was to examine the occurrence and magnitude of effects of slackline
      training compared with an inactive control condition on static and dynamic
      balance performance parameters in children, adults and seniors. DATA SOURCES:
      Five biomedical and psychological databases (CINAHL, EMBASE, ISI Web of
      Knowledge, PubMed, SPORTDiscus) were screened using the following search terms
      with Boolean conjunctions: (slacklin* OR slack-lin* OR tight rop* OR tightrop* OR
      Slackline-based OR line-based OR slackrop* OR slack-rop* OR floppy wir* OR rop*
      balanc* OR ropedanc* OR rope-danc*) STUDY SELECTION: Randomized and non
      randomized controlled trials that applied slackline training as an exercise
      intervention compared with an inactive control condition focusing on static and
      dynamic balance performance (perturbed and non-perturbed single leg stance) in
      healthy children, adults and seniors were screened for eligibility. DATA
      EXTRACTION: Eligibility and study quality [Physiotherapy Evidence Database
      (PEDro) scale] were independently assessed by two researchers. Standardized mean
      differences (SMDs) calculated as weighted Hedges' g served as main outcomes in
      order to compare slackline training versus inactive control on slackline standing
      as well as dynamic and static balance performance parameters. Statistical
      analyses were conducted using a random-effects, inverse-variance model. RESULTS:
      Eight trials (mean PEDro score 6.5 +/- 0.9) with 204 healthy participants were
      included. Of the included subjects, 35 % were children or adolescents, 39 % were
      adults and 26 % were seniors. Slackline training varied from 4 to 6 weeks with 16
      +/- 7 training sessions on average, ranging from 8 to 28 sessions. Mean overall
      slackline training covered 380 +/- 128 min. Very large task-specific effects in
      favor of slackline training compared with the inactive control condition were
      found for slackline standing time {SMD 4.63 [95 % confidence interval (CI) 3.67
      5.59], p < 0.001}. Small and moderate pooled transfer effects were observed for
      dynamic [SMD 0.52 (95 % CI 0.08-0.96), p = 0.02] and static [SMD 0.30 (95 % CI 
      0.03 to 0.64), p = 0.07] standing balance performance, respectively. CONCLUSIONS:
      Slackline training mainly revealed meaningful task-specific training effects in
      balance performance tasks that are closely related to the training content, such
      as slackline standing time and dynamic standing balance. Transfer effects to
      static and dynamic standing balance performance tasks are limited. As a
      consequence, slackline devices should be embedded into a challenging and
      multimodal balance training program and not used as the sole form of training.

PMID- 27704484
TI  - Effect of Plyometric Training on Vertical Jump Performance in Female Athletes: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Plyometric training is an effective method to prevent knee injuries
      in female athletes; however, the effects of plyometric training on jump
      performance in female athletes is unclear. OBJECTIVE: The aim of this systematic
      review and meta-analysis was to determine the effectiveness of plyometric
      training on vertical jump (VJ) performance of amateur, collegiate and elite
      female athletes. METHODS: Six electronic databases were searched (PubMed,
      MEDLINE, ERIC, Google Scholar, SCIndex and ScienceDirect). The included studies
      were coded for the following criteria: training status, training modality and
      type of outcome measures. The methodological quality of each study was assessed
      using the physiotherapy evidence database (PEDro) scale. The effects of
      plyometric training on VJ performance were based on the following standardised
      pre-post testing effect size (ES) thresholds: trivial (<0.20), small (0.21-0.60),
      moderate (0.61-1.20), large (1.21-2.00), very large (2.01-4.00) and extremely
      large (>4.00). RESULTS: A total of 16 studies met the inclusion criteria. The
      meta-analysis revealed that plyometric training had a most likely moderate effect
      on countermovement jump (CMJ) height performance (ES = 1.09; 95 % confidence
      interval [CI] 0.57-1.61; I 2 = 75.60 %). Plyometric training interventions of
      less than 10 weeks in duration had a most likely small effect on CMJ height
      performance (ES = 0.58; 95 % CI 0.25-0.91). In contrast, plyometric training
      durations greater than 10 weeks had a most likely large effect on CMJ height (ES
      = 1.87; 95 % CI 0.73-3.01). The effect of plyometric training on concentric-only
      squat jump (SJ) height was likely small (ES = 0.44; 95 % CI -0.09 to 0.97).
      Similar effects were observed on SJ height after 6 weeks of plyometric training
      in amateur (ES = 0.35) and young (ES = 0.49) athletes, respectively. The effect
      of plyometric training on CMJ height with the arm swing was likely large (ES =
      1.31; 95 % CI -0.04 to 2.65). The largest plyometric training effects were
      observed in drop jump (DJ) height performance (ES = 3.59; 95 % CI -3.04 to
      10.23). Most likely extremely large plyometric training effects on DJ height
      performance (ES = 7.07; 95 % CI 4.71-9.43) were observed following 12 weeks of
      plyometric training. In contrast, a possibly small positive training effect (ES =
      0.30; 95 % CI -0.63 to 1.23) was observed following 6 weeks of plyometric
      training. CONCLUSION: Plyometric training is an effective form of training to
      improve VJ performance (e.g. CMJ, SJ and DJ) in female athletes. The benefits of
      plyometric training on VJ performance are greater for interventions of longer
      duration (>=10 weeks).

PMID- 27704485
TI  - Health Care Utilization and Costs Associated with Nausea and Vomiting in Patients
      Receiving Oral Immediate-Release Opioids for Outpatient Acute Pain Management.
AB  - INTRODUCTION: Nausea and vomiting (NV) are common side effects of opioid use and
      limiting factors in pain management. This study sought to quantify the frequency
      of antiemetic prescribing and the impact of NV on health care resource
      utilization and costs in outpatients prescribed opioids for acute pain. The
      perspective was that of a commercial health plan. METHODS: Medical and pharmacy
      claims from IMS PharMetrics Plus were used to identify patients initiating opioid
      therapy with a prescription for an oxycodone-, hydrocodone- or codeine-containing
      immediate-release product for acute use (<=15-day supply) between October 1, 2013
      and September 30, 2014. Patients with a medical claim for NV (International
      Classification of Diseases, Ninth Revision, Clinical Modification codes 787.0x),
      with or without an antiemetic prescription fill, were compared with patients with
      no NV claim or antiemetic prescription fill to assess differences in all-cause
      health care utilization and costs over 1 month. Propensity score matching (PSM)
      was used to adjust for between-group differences in baseline patient
      characteristics. RESULTS: The co-prescribing of opioids with antiemetic agents
      was 10.2%. After PSM (n = 45,790 per group), patients with NV claims had
      significantly more hospitalizations (11.5% vs 4.2%), emergency department visits
      (65.0% vs 12.1%), and physician office visits (85.2% vs 64.5%) compared with
      patients with no NV claims (all P < 0.0001). Mean total health care costs were
      higher among patients with a NV claim versus those without evidence of the side
      effect ($6290 vs $2309; P < 0.0001). Among patients with a recent
      hospitalization, patients with NV claims had higher rates of 30-day
      rehospitalization than those with no NV claims (24.4% vs 3.0%; P < 0.0001).
      CONCLUSIONS: Among outpatients prescribed opioids for management of acute pain,
      co-prescribing with antiemetics was low, and the economic burden associated with
      NV was high. Efforts to prevent NV in patients receiving opioid therapy may
      improve patient outcomes and provide cost savings to the health care system.
      FUNDING: Daiichi Sankyo, Inc.

PMID- 27704487
TI  - Chemical Composition of Nanoporous Layer Formed by Electrochemical Etching of p
      Type GaAs.
AB  - We have performed a detailed characterization study of electrochemically etched p
      type GaAs in a hydrofluoric acid-based electrolyte. The samples were investigated
      and characterized through cathodoluminescence (CL), X-ray diffraction (XRD),
      energy-dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy
      (XPS). It was found that after electrochemical etching, the porous layer showed a
      major decrease in the CL intensity and a change in chemical composition and in
      the crystalline phase. Contrary to previous reports on p-GaAs porosification,
      which stated that the formed layer is composed of porous GaAs, we report evidence
      that the porous layer is in fact mainly constituted of porous As2O3. Finally, a
      qualitative model is proposed to explain the porous As2O3 layer formation on p
      GaAs substrate.

PMID- 27704486
TI  - Successful Stepwise Development of Patient Research Partnership: 14 Years'
      Experience of Actions and Consequences in Outcome Measures in Rheumatology
      (OMERACT).
AB  - There is increasing interest in making patient participation an integral
      component of medical research. However, practical guidance on optimizing this
      engagement in healthcare is scarce. Since 2002, patient involvement has been one
      of the key features of the Outcome Measures in Rheumatology (OMERACT)
      international consensus effort. Based on a review of cumulative data from
      qualitative studies and internal surveys among OMERACT participants, we explored
      the potential benefits and challenges of involving patient research partners in
      conferences and working group activities. We supplemented our review with
      personal experiences and reflections regarding patient participation in the
      OMERACT process. We found that between 2002 and 2016, 67 patients have attended
      OMERACT conferences, of whom 28 had sustained involvement; many other patients
      contributed to OMERACT working groups. Their participation provided face validity
      to the OMERACT process and expanded the research agenda. Essential facilitators
      have been the financial commitment to guarantee sustainable involvement of
      patients at these conferences, procedures for recruitment, selection and support,
      and dedicated time allocated in the program for patient issues. Current
      challenges include the representativeness of the patient panel, risk of pseudo
      professionalization, and disparity in patients' and researchers' perception of
      involvement. In conclusion, OMERACT has embedded long-term patient involvement in
      the consensus-building process on the measurement of core health outcomes. This
      integrative process continues to evolve iteratively. We believe that the
      practical points raised here can improve participatory research implementation.

PMID- 27704488
TI  - Efficiency of an electronic device in controlling tracheal cuff pressure in
      critically ill patients: a randomized controlled crossover study.
AB  - BACKGROUND: Despite intermittent control of tracheal cuff pressure (P cuff) using
      a manual manometer, cuff underinflation (<20 cmH2O) and overinflation (>30 cmH2O)
      frequently occur in intubated critically ill patients, resulting in increased
      risk of microaspiration and tracheal ischemic lesions. The primary objective of
      our study was to determine the efficiency of an electronic device in continuously
      controlling P cuff. The secondary objective was to determine the impact of this
      device on the occurrence of microaspiration of gastric or oropharyngeal
      secretions. METHODS: Eighteen patients requiring mechanical ventilation were
      included in this prospective randomized controlled crossover study. They randomly
      received either continuous control of P cuff with Mallinckrodt(r) device for 24
      h, followed by discontinuous control with a manual manometer for 24 h, or the
      reverse sequence. During the 48 h after randomization, P cuff was continuously
      recorded, and pepsin and alpha amylase were quantitatively measured in tracheal
      aspirates. P cuff target was 25 cmH2O. RESULTS: Clinical characteristics were
      similar during the two study periods, as well as mean airway pressure. Percentage
      of time spent with cuff overinflation or underinflation was significantly lower
      during continuous control compared with routine care period [median (IQR) 0.8
      (0.1, 2) vs 20.9 (3.1, 40.1), p = 0.0009]. No significant difference was found in
      pepsin [median (IQR) 230 (151, 300) vs 259 (134, 368), p = 0.95] or in alpha
      amylase level [median (IQR) 1475 (528, 10,333) vs 2400 (1342, 15,391), p = 0.19]
      between continuous control and routine care periods, respectively. CONCLUSIONS:
      The electronic device is efficient in controlling P cuff, compared with routine
      care using a manometer. Further studies are needed to evaluate the impact of this
      device on intubation-related complications. Trial registration ClinicalTrials.gov
      Identifier: NCT01965821.

PMID- 27704489
TI  - Influence of Depression and Hostility on Exercise Tolerance and Improvement in
      Patients with Coronary Heart Disease.
AB  - PURPOSE: Although hostility and depression have been linked to higher cardiac
      risk and poor prognosis of patients with coronary heart disease (CHD), there is a
      lack of research that studies how they may influence the short-term outcomes
      among patients participating in cardiac rehabilitation (CR). This study aimed to
      investigate the influence of hostility and depression on patients' exercise
      tolerance and improvement trajectory in a CR program over 6 weeks. METHOD:
      Participants were 142 patients with CHD, with a mean age of 62 years. Latent
      growth curve modeling was conducted to determine whether hostility and depression
      predicted patients' baseline exercise tolerance and rates of improvement on
      treadmill, while controlling for age and severity of illness. In addition,
      analysis was conducted to examine whether depression mediated the influence of
      hostility on exercise outcomes. RESULTS: Patients with CHD with higher hostility
      scores had a lower baseline exercise tolerance and slower rates of improvement
      over 6 weeks. Depressive symptom severity mediated the influence of hostility on
      exercise baseline and improvement. Patients with higher hostility were more
      likely to have more severe depressive symptoms, which in turn were associated
      with lower baseline exercise tolerance and slower improvement. CONCLUSION: While
      both hostility and depression predicted the exercise outcomes in CR, depression
      explained the influence of hostility. The findings underscore the importance of
      addressing psychosocial issues in treatment of CHD patients and provide support
      for psychosocial interventions in CR to facilitate patients' recovery.

PMID- 27704491
TI  - Preventing Maternal Morbidity from Obstetric Hemorrhage: Implications of a
      Provider Training Initiative (Podcast).

PMID- 27704490
TI  - Enlightening the Cerebellopontine Angle: Intraoperative Indocyanine Green
      Angiography in Microvascular Decompression for Trigeminal Neuralgia.
AB  - Background and Study Aims In microvascular decompression of the trigeminal nerve
      for trigeminal neuralgia (TN), the site of conflict is occasionally difficult to
      identify. Endoscopy has been described to better evaluate the anatomical conflict
      in such situations. We hypothesized that indocyanine green (ICG) angiography
      could allow for better visualization of the compressing artery and its anatomical
      relation to the nerve. Material and Methods ICG angiography was performed in 17
      TN patients undergoing microvascular decompression. We focused on whether ICG
      angiography is helpful in determining the site of conflict, particularly when not
      directly visible via the microscope, and whether fluorescence is strong enough to
      shine through the nerve obliterating the direct view of the compressing vessel.
      Results In four patients, the site of conflict was immediately apparent after
      opening the cerebellopontine cistern, and ICG angiography did not provide the
      neurosurgeon with additional information. In another two patients, imaging
      quality and fluorescence were too poor. Of the remaining 11 patients with a
      hidden site of nerve-vessel conflict, ICG angiography was found to be helpful in
      anticipating the site of compression and the course of the artery in 7 patients,
      particularly in regard to the so-called shining-through effect through fiber
      bundles of the thinned nerve. Of all the patients, 88% reported at least
      improvement or cessation of their symptoms, including all of the patients with a
      shine-through effect. Conclusion ICG angiography could be a helpful adjunct in
      decompressing the trigeminal nerve and can guide the surgeon to the nerve-vessel
      conflict. Intensity of the fluorescence is powerful enough to shine through
      thinned and splayed trigeminal nerve fiber bundles.

PMID- 27704492
TI  - Association among Maternal Obesity, Cervical Length, and Preterm Birth.
AB  - Objective The objective of this study was to determine if mid-trimester cervical
      length is associated with the inverse relationship between maternal body mass
      index (BMI) at delivery and spontaneous preterm birth (SPTB). Materials and
      Methods This was a retrospective cohort of women with a singleton pregnancy
      without prior SPTB who underwent routine transvaginal cervical length assessment
      between 18 and 24 weeks. Women were categorized into four BMI groups: (1) 18.5 to
      24.9, (2) 25 to 29.9, (3) 30 to 34.9, and (4) >= 35 kg/m2. Univariable and
      multivariable analyses were conducted to determine whether BMI group was
      associated with SPTB at < 37, 34, or 32 weeks independent of the cervical length.
      Results Of the 18,100 women in this analysis, 43.5% had a BMI >= 30. In
      univariable analysis, increasing BMI group was associated with longer cervical
      length but not with cervical length < 10th percentile. SPTB at < 37, 35, and 32
      weeks was less common among women with higher BMI. In multivariable regression, a
      higher BMI group was associated with a lower frequency of SPTB at 37 weeks
      (adjusted odds ratios [aORs] of 0.64, 0.68, and 0.51), at 34 weeks (aORs of 0.53,
      0.54, and 0.31) and at 32 weeks (aORs of 0.47, 0.60, and 0.27) for BMI groups 2
      to 4, respectively. This association persisted even when cervical length was
      entered into the model as a covariate. Conclusion Women with a higher BMI group
      had longer mid-trimester cervical length, and correspondingly reduced SPTB.
      However, the decreased risk of SPTB was not associated with cervical length. The
      reason for the potential protective effect from prematurity is unknown and its
      mechanisms require further investigation.

PMID- 27704493
TI  - Justin C. McArthur, MBBS, MPH, FAAN, FANA, and Nicoline Schiess, MD, MPH.

PMID- 27704494
TI  - Pearls and Pitfalls, Part 2.

PMID- 27704495
TI  - Neuromuscular Diseases.
AB  - Neuromuscular diseases are a broadly defined group of disorders that all involve
      injury or dysfunction of peripheral nerves or muscle. The site of injury can be
      in the cell bodies (i.e., amyotrophic lateral sclerosis [ALS] or sensory
      ganglionopathies), axons (i.e., axonal peripheral neuropathies or brachial
      plexopathies), Schwann cells (i.e., chronic inflammatory demyelinating
      polyradiculoneuropathy), neuromuscular junction (i.e., myasthenia gravis or
      Lambert-Eaton myasthenic syndrome), muscle (i.e., inflammatory myopathy or
      muscular dystrophy), or any combination of these sites. Some neuromuscular
      diseases are also associated with central nervous system disease, such as ALS,
      but most are restricted to the peripheral nervous system. The multitude of
      possible sites of injury can make neuromuscular diseases difficult to diagnose.
      Here the author reviews key features of the clinical presentation that help
      localize the site of injury and some basic tenets of electromyography. He then
      shares several pearls in diagnosing and treating patients with specific
      neuromuscular diseases.

PMID- 27704496
TI  - Myasthenia Gravis.
AB  - The basic abnormality in myasthenia gravis (MG) is a reduction in acetylcholine
      receptors (AChRs) at neuromuscular junctions due to the effects of autoantibodies
      that are directed against the AChRs in most patients, or against neighboring
      proteins involved in the clustering of AChRs (MuSK, LRP-4, or agrin). Clinically,
      MG is characterized by muscle weakness and fatigue, often in typical patterns.
      The diagnosis may be missed early, and depends on the recognition of clinical
      manifestations, the measurement of autoantibodies, and/or electrophysiological
      features. The treatment of MG involves the enhancement of neuromuscular
      transmission by anticholinesterase drugs (pyridostigmine), and by immunotherapy.
      Therapy should be designed to improve the clinical features quickly, and keep the
      symptoms in abeyance over the long term. Rapid improvement can be achieved when
      necessary by the administration of intravenous immunoglobulin or plasma exchange.
      Intermediate rates of improvement over months involve the use of adrenal
      corticosteroids, the calcineurin inhibitors cyclosporine or tacrolimus, and in
      some patients, the B-cell inhibitor rituximab. For long-term treatment,
      mycophenolate and azathioprine are the most effective agents. A thymectomy may
      also have long-term beneficial effects. The majority of MG patients can live
      normal lives, but most patients require lifelong treatment. The physician's skill
      in managing the immunotherapeutic agents and avoiding adverse side effects is of
      paramount importance in the treatment of MG.

PMID- 27704497
TI  - Acute Visual Loss.
AB  - Acute visual loss is a frightening experience, a common ophthalmic emergency, and
      a diagnostic challenge. In this review, the author focusses on the diagnosis of
      transient monocular blindness and visual loss due to infarction of the retina
      and/or the optic nerve-the ocular parallel of cerebral stroke.

PMID- 27704498
TI  - Dizziness.
AB  - Dizziness and vertigo are among the most common symptoms to bring a patient to a
      neurologist. Because symptoms are often vague and imprecise, a systematic
      approach is essential. By categorizing vestibular disorders based on timing,
      triggers, and duration, as well as through focused oculomotor and vestibular
      examinations, the vast majority of neuro-otologic diagnoses can be made at the
      bedside. Here the authors discuss historical and examination pearls for the most
      common neuro-otologic disorders.

PMID- 27704499
TI  - Headache.
AB  - Headache disorders are primarily managed in an outpatient setting; therefore, the
      authors focus on the primary headache disorders that comprise the bulk of
      clinical practice. Red flags for secondary headaches that may be more commonly
      encountered in clinic are briefly discussed.

PMID- 27704500
TI  - Sleepiness.
AB  - Sleep medicine can be a particularly rewarding clinical area for neurologists.
      After all, the driving organ of sleep is the brain. Many of the sleep disorders
      are primary brain disorders, whereas other sleep disorders (and their
      medications) influence brain function. But without an organized approach, even
      the engaged and motivated neurologist can easily become frustrated when dealing
      with patients whose concerns center on an undesirable degree of sleepiness. Lost
      in the thicket of information provided during the patient-doctor encounter, many
      physicians are unable to direct the history toward particular diagnostic
      hypotheses. So, rather than provide an exhaustive and disorganized set of details
      about sleep medicine, the author instead shares pearls of sleep medicine in the
      context of an overall framework, with the goal to foster targeted history-taking
      for the successful diagnosis of a patient struggling with maintaining
      wakefulness. The topic of excessive sleepiness will be covered because it is so
      common and because its mastery is fundamental to approaching most patients with
      sleep disorders. Common and important pitfalls regarding the topic of sleepiness
      and how to avoid them-will be discussed. Misdiagnoses and mismanagement are easy
      to avoid if this entire framework is kept in mind.

PMID- 27704501
TI  - Low Back Pain and Spondylosis.
AB  - Low back pain is highly prevalent, affecting a vast majority of the adult
      population at some point in their lifetime. Thorough history and physical
      examination is critically important in evaluating these patients and screening
      for potentially serious conditions. Imaging should be guided by the history and
      physical examination, particularly when there is concern for serious conditions
      and/or a focal neurological deficit present. Adequate treatment of patients with
      low back pain often requires a multidisciplinary approach, involving several
      medical specialties. Patients with acute axial low back pain typically have a
      favorable prognosis with resolution over 4 weeks, regardless of treatment.
      However, patients with chronic low back pain should be transitioned to pain
      management strategies with multidisciplinary care, in order to maximize function
      and limit disability. Referral to a spine surgeon is indicated urgently for a
      severe, progressive neurological deficit, particularly new motor weakness or
      cauda equina syndrome, and can be done electively for patients with degenerative
      disorders without a focal deficit.

PMID- 27704502
TI  - Neuropathic Pain.
AB  - Diagnosing neuropathic pain and distinguishing it from nociceptive pain can be
      challenging, but is essential because both forms of pain require different
      treatment strategies. The diagnosis of neuropathic pain is primarily based on
      clinical findings. Therefore, a careful, focused history and an examination of
      the signs characteristic of neuropathic pain are crucial. Imaging techniques and
      electrophysiological examinations, as well as punch skin biopsy can support the
      clinical diagnosis. Ideally, treatment should be individualized using a mechanism
      based approach. However, current treatments are usually dispensed without
      precision, and calcium-channel-acting modulators (pregabalin, gabapentin),
      tricyclic antidepressants, and serotonin-noradrenalin reuptake inhibitors
      (duloxetine, venlafaxine) represent first-line treatment options for neuropathic
      pain. Although neurostimulation techniques for the treatment of refractory
      chronic pain have become more important, most evidence of long-term effectiveness
      and safety is still limited, which strengthens the need for larger randomized
      controlled trials before final recommendations can be made.

PMID- 27704503
TI  - Myofascial Trigger Point Pain Syndromes.
AB  - Myofascial pain syndromes caused by trigger points (TrPs) in muscle are a common
      cause of local and generalized pain. Trigger points are hyperirritable zones in
      contracted bands of muscle, thought to be caused by muscle overload or stress.
      Stress TrPs have characteristic electromyographic features, and can be visualized
      with ultrasound and magnetic resonance elastography. Trigger point needling or
      injection can be effective in inactivating TrP, but correcting triggers is also
      critical.

PMID- 27704504
TI  - Gait and Balance Assessment.
AB  - Gait and balance deficits are commonly experienced by individuals with a variety
      of neurologic disorders. These deficits can be particularly frustrating because
      they often profoundly impact a person's quality of life. The author applies
      information about gait and balance based on the neurologic examination and
      summarizes important relationships among common impairment measures of gait and
      balance deficits. She also provides an interpretation of these relationships to
      assist the clinician in how to identify and manage gait and balance deficits.

PMID- 27704505
TI  - Prof. Daniel H. Teitelbaum, MD (1957-2016).

PMID- 27704506
TI  - Item analysis of examinations in the Faculty of Medicine of Tunis.
AB  - Introduction Item analysis is the process of collecting, summarizing and using
      information from students' responses to assess test items' quality. This study
      used this approach to evaluate the quality of items and examinations given in the
      Faculty of Medicine of Tunis (FMT).    Methods This study concerned the
      examinations of 2012-2013 (principal session). It analyzed 3138 items from 66
      examinations, of which, 46 were multidisciplinary (187 disciplines). A total of
      2515 students took the examinations. "AnItem.xls" file was used for the analysis
      that focused on difficulty, discrimination and internal consistency.  Results
      Mean difficulty for all examinations was optimum (mean difficulty index: 0.59).
      Majority of items (89.17%) were either easy or of acceptable difficulty. Mean
      discrimination for all examinations was moderate (mean item discrimination
      coefficient: 0.28) with poor discrimination in 23.62% of items. Maximal
      discrimination occurred with disciplines of difficulty index between 0.4-0.6. "
      Ideal " items represented 27.02%. Mean internal consistency for all examinations
      was acceptable (Cronbach's alpha: 0.79). Disciplines with nonacceptable internal
      consistency (68.45%) contained a maximum of 33 items (each one) and a positive
      correlation between their alpha and the number of their questions. Distributions
      were mostly (72.73%) platykurtic and negatively asymmetric (89.39%). First year
      of studies had the best parameters. Conclusion Our examinations had an acceptable
      internal consistency, and a good level of difficulty and discrimination. They
      tended to facility and discriminated basically students of medium level. Item
      analysis is useful as a guide to item writers to improve the overall quality of
      questions in the future.

PMID- 27704507
TI  - Comparison of two oxytocin administration protocols in elective cesarean section:
      5 iu versus 10 iu.
AB  - Background Although Oxytocin is used systematically during caesarean section, no
      recommendation precise optimal dose for this indication. The bolus administration
      of 10 IU intravenously after extraction of the newborn, is accompanied by side
      effects mainly hemodynamic. Objectives To compare two Oxytocin protocols:  05 IU
      bolus Vs. 10 IU bolus during Cesarean section by studying their respective
      effectiveness (effects on uterine tone) and adverse effects. Methods A
      prospective randomized double-blind study including 87 term parturients for
      undergoing a C-section under loco regional anesthesia. Parturients were
      randomized into two groups depending on the injected Oxytocine dose : - Group 1
      (n = 43): 10 IU + 25 IU IVD in 500 ml of serum / 3h - Group 2 (n = 44): 5 IU IVD
      + 25 IU in 500 ml serum / 3h. Results The variation of the heart rate and the
      incidence of low blood pressure were significantly greater for Group 1. No
      significant differences between the two groups regarding blood loss was noticed
      per or postoperatively. The type of digestive side effects were more common in
      the first group. Conclusion Administration of 5 units of Oxytocin during the
      scheduled C-sections is effective for uterine tone without superimposed bleeding
      risk, guarantees better hemodynamic stability and less side effects than the 10
      units dose.

PMID- 27704508
TI  - Childhood tuberculosis: A descriptive study in a pneumo-pediatrics department in
      Tunisia.
AB  - Objective to assess the different localizations of tuberculosis (TB) in children
      in a pneumopediatric department in Tunisia and to describe its diagnosis tools
      since clinical investigations of childhood TB are challenged by the
      paucibacillary nature of the disease and the difficulties in obtaining specimens.
      Methods Forty-six cases of TB in children were studied between 2008 and 2013.
      Clinical history, examination and chest radiography were reported. Several
      investigations have been conducted to confirm the diagnosis of TB such as:
      tuberculin skin test (TST), bacteriological and histological investigations. Anti
      tuberculosis treatment was prescribed according to the national guidelines.
      Results Cough and deterioration in general condition were the most frequent
      symptoms (47.8% and 43.7%). The other children presented cervical swelling
      (19.5%), chest pain (17.4%) and hemoptysis (4.3%). Abnormalities have been found
      in chest radiography in 35 cases (76%). TST was positive in 73% of cases.
      Diagnosis of TB was confirmed in 56.6% of cases by Mycobacterium tuberculosis
      (MT) isolation and/or biopsy. The diagnosis was made on presumptive arguments in
      20 cases (43.4%) based on a history of TB contact, suggestive symptoms and a
      positive TST. A surgical biopsy was necessary for diagnosis in 17 cases
      (nasopharynx, bone, cervical, mediastinal and mesenteric lymph nodes). Pulmonary
      TB was diagnosed in 52% of cases. Two children were diagnosed with disseminated
      TB. A diagnosis delay was noted with an average of 20 days and a contact history
      was found in 52% of the children. All children were treated according to the
      national guidelines without major side effects. Healing without sequelae was
      achieved in 91% of cases. Conclusion Children represent a population at high risk
      for TB especially after a household contact with a higher frequency of multifocal
      forms compared to adults. The difficulty of the diagnosis in children may explain
      partially the diagnosis delay, but efforts must be done to improve prevention and
      diagnosis in our country.

PMID- 27704509
TI  - Spectral Domain optical coherence tomography findings in patients with retinitis
      pigmentosa.
AB  - Background Maculopathy is a common complication of retinitis pigmentosa (RP), and
      compromise the visual acuity of RP patients even in the less advanced stages. Aim
      To report the morphological macular findings detected by spectral domain optical
      coherence tomography (SD-OCT) and to determine their prevalence in patients with
      retinitis pigmentosa (RP). Methods  SD-OCT scans from 100 patients (196 eyes)
      affected by RP were reviewed. Results We noted a normal macula appearance in
      48.5%, macular edema in 14.5% and macular atrophy in 37%. Mean central macular
      thickness was 167.79 microns and we did not note any statistically significant
      correlation between visual acuity and foveal thickness. Visual acuity was
      statistically better in eyes with a larger number of hyper-reflective layers
      (p<0.001) and in eyes with photoreceptor inner/outer (IS/OS) segment junction
      distinct (p<0.001). We have identified three types of tomographic macular edema:
      a cystoids macular edema in 6.8%, a tractional edema in 8.2% and mixed edema in
      1%. We identified two tomographic types of macular atrophy: a central- foveal
      atrophy in 34 eyes (11.6%) and diffuse atrophy in 38 eyes (12.9%). Epiretinal
      membrane was present in 24 eyes (8.2%). Conclusions The OCT contributes to the
      analysis of epidemiological and morphological of different macular involvement in
      RP. OCT has a prognostic value, which essentially depends on the morphology of
      the IS/OS line and number of hyper-reflective layers.

PMID- 27704510
TI  - Nephrocalcinosis in Tunisian children.
AB  - Background Nephrocalcinosis is rare in children. Its etiologies are multiple. The
      aim of this study was to analyze the etiology of nephrocalcinosis in Tunisian
      children. Methods This retrospective study was conducted in the department of
      pediatrics in Charles Nicolle Hospital during a period of 10 years (2001-2010).
      Results There were 40 children. The mean age was 3.5 years. The most common signs
      and symptoms at presentation were growth retardation (42.5%) and hematuria
      (53.8%). At presentation, renal failure was detected in 70% of patients. The
      diagnosis of nephrocalcinosis was performed by ultrasonography. The etiology of
      nephrocalcinosis included primary hyperoxaluria type 1 (65%) and distal renal
      tubular acidosis (20%). A progression to renal insufficiency was observed in 18
      cases. Conclusion Primary oxaluria is the principal cause of nephrocalcinosis;
      early diagnosis and treatment are mandatory as they help limiting renal function
      deterioration.

PMID- 27704512
TI  - What prognosis for Ebstein's anomaly without surgery? Hassan II teaching hospital
      experience.
AB  - Background From the first description in 1886, significant progress was made on
      the treatment of Ebstein disease by mono and bi-ventricular surgery. Aim To
      highlight the prognosis of Ebstein's anomaly in the pediatric department of
      Hassan II hospital in Fez. Methods This is a descriptive and retrospective study
      of 4 years. Results We collected nine patients (seven boys and two girls) with a
      mean age of 5.3 years. Cyanosis was the main mode of revelation of the disease.
      In three patients Ebstein's anomaly was part of a malformative syndrome. All
      patients had only symptomatic medical treatment. Five patients are still alive at
      a follow up of one to six years. Conclusion Symptomatic medical treatment of
      Ebstein malformation may improve the prognosis of the disease.

PMID- 27704511
TI  - Protective effect of Ulva lactuca extract during hepatic cold preservation in
      rats.
AB  - Introduction In recent years, many marine resources have drew attention in the
      research for bio-active compounds to develop new drugs and health foods. (1)
      Marine algae are now considered as a rich source of antioxidants (2). It is known
      that seaweeds contain numerous bioactive substances that have the ability to
      lower cholesterol, reduce blood pressure, promote healthy digestion; and
      antioxidant activity (3). Natural antioxidants are interesting compounds due to
      their properties which help prevent oxidative stress (4), among other potentially
      beneficial actions. For instance, several biological effects have been attributed
      to flavonoids, such as anti-tumoral, anti-inflammatory, anti-ischemic and anti
      aggregate plaquetary activities. These activities are believed to be in part
      related to the antioxidant properties of the compounds, namely in scavenging
      radical oxygen species (ROS). (5, 6) The cold ischemia constitute a situation of
      oxidative stress in touch with liberation of oxygenated radicals, these
      situations incited the researchers to find means for the improvement of the
      conservation of organs allowing to prolong the durations of the cold ischemia of
      certain organs (in particular the liver) with conservation of the maximum
      functional value. However, the constant efforts led by the teams of
      transplantation to develop transplants, the conservation of organs remains a
      problem to be resolved. (7) Conservation solution of organ appears as being a
      stemming to remedy the fatal effects of the ischemia-reperfusion. For our part,
      we think that seaweeds have not delivered their secrets and yet especially that
      the marine environment of the Tunisian coast still remains little exploited in
      spite of the big variety of the fauna and the flora of the coast. We envisage in
      this work, to study a sort of seaweed collected on the Tunisian quotation in the
      region of "Chott Meriem" (North West of Tunisia). The purpose of our work is to
      estimate the capacity of extracts stemming from the green seaweed Ulva lactuca to
      improve the conservation solution of organs against the hepatic effects of
      ischemia.

PMID- 27704513
TI  - Community-acquired pleuropneumonia in children: Bacteriological and therapeutic
      challenges.
AB  - Background Community-acquired pleuropneumonia (CPP) is a common complication of
      pneumonia in children. It is serious given its high morbidity and significant
      mortality. Aim To study clinical and paraclinical features of CPP in children and
      to establish a common therapeutic strategy. Methods Our retrospective study
      included patients who were hospitalized for CPP between 2004 and 2012. All data
      were collected from patients' medical files. Statistical analysis was made by Epi
      Info 6. Results One hundred and sixty four patients were registered. The mean age
      was 32 months (15 days - 14.5 years). The hospital incidence of CPP doubled
      between 2004 and 2012. The symptomatology was dominated by fever (93.9%), cough
      (56.7%) and dyspnea (48.1%). The pleural effusion was frequently moderately
      abundant and loculated. Pleural sample, performed in 53.6% of cases, was the most
      beneficial bacteriological examination (p=10-6 ). The bacteriological
      confirmation was attained in 44.5% of cases with the predominance of
      Staphylococcus aureus (59%) followed by Streptococcus pneumoniae (26%). The S.
      aureus occurred basically in most young infants (p=0.04) and was responsible for
      the most severe cases (p=0.01). The CPP management included heterogeneous
      intravenous antibiotics associated with a pleural drainage in 40% of cases. The
      quarter of our patients were transferred to an intensive care unit. Six patients
      died. Conclusion The bacteriological confirmation is difficult. Pleural
      aspiration is the key tool. S. aureus is the first microorganism followed by S.
      pneumoniae. A therapeutic strategy is proposed based on large spectrum
      intravenous antibiotics. The pleural drainage indication is limited.

PMID- 27704514
TI  - Prevalence of overweight in schools in the rural region of Hazoua (Tozeur).
AB  - Background Overweight in schools is a worrisome public health problem because
      they increase medium and long term risks of morbidity and mortality especially
      with an increased risk of persistence of obesity in adulthood. Aim To estimate
      the prevalence of overweight among school children and to identify its associated
      risk factors. Methods this is a descriptive cross-sectional study conducted among
      school students aged less than 18 years in the area of "Hazoua" (Tozeur). The
      references of BMI used for overweight and obesity are those of IOTF. The French
      BMI references are used to establish the prevalence of underweight. Data entry
      and analysis was performed using SPSS 20. Results Our sample included 445
      students. The average BMI was 18.73+/-3.4 kg/m2. The prevalence of Underweight
      was 9.7%, while overweight and obesity have been reported among 6.7% of students.
      Overweight was significantly associated to gender and the practice of sport
      outside school. Conclusion Obesity in schools in the community of Hazoua is now
      lower than that reported in other studies. In contrast, we detected a problem of
      underweight, which deserves as much attention. Intervention programs should be
      established and whose objectives are to improve students' skills in terms of
      eating behavior and physical activity, these actions require collaboration at all
      levels.

PMID- 27704515
TI  - Prevalence and outcomes of thrombocytopenia in a neonatal intensive care unit.
AB  - Background Thrombocytopenia is a common clinical problem in neonatal intensive
      care units, affecting about 20 to 35% of all admitted neonates. Even most
      episodes are mild or moderate, severe episodes could be life-threatening or
      responsible for sequelae. Objectives The aims of this study were to describe the
      prevalence, clinical diagnoses, and to determine risk factors for poor prognosis
      of thrombocytopenia in a neonatal intensive care unit. Methods We carried out a
      retrospective study in the neonatal intensive care unit of Charles Nicolle
      Hospital of Tunis, a tertiary neonatal care center, over a four years period
      (January 2010 to December 2013). All Neonates with at least one episode of
      confirmed thrombocytopenia were included. Poor prognosis was defined as death or
      intraventricular hemorrhage >= grade 2 in survivors. Results Of 808 admitted
      neonates, one hundred (12.4%) had presented at least one episode of confirmed
      thrombocytopenia, and 12 had presented two episodes of thrombocytopenia. A total
      of 112 episodes of thrombocytopenia were collected. Thrombocytopenia occurred in
      the first 3 days of life in 74.1% of cases. Thrombocytopenia was mild in 22.3%,
      moderate in 36.7% and severe in 41%. Intrauterine growth restriction was the most
      common cause of early thrombocytopenia. Nosocomial sepsis was the most common
      cause of late thrombocytopenia. We found that the outcomes of thrombocytopenic
      neonates depend on, birth weight, gestational age, platelet count, and the
      underlying cause. Conclusions Thrombocytopenia in neonates can be life
      threatening, appropriate diagnosis, preventive and therapeutic approach is
      necessary to prevent death or neurological impairment.

PMID- 27704516
TI  - Prognostic factors in children with extracranial malignant germ cell tumors: a
      monocentric pediatric Tunisian study.
AB  - Background Extracranial Germ cell tumors (GCT) are a rare and a heterogeneous
      group of pediatric cancers but highly curable. Aim We aimed to review management,
      outcome and prognostic factors that influence overall survival (OS) in a
      pediatric Tunisian oncologic unit. Methods We retrospectively evaluated between
      January 1998 and December 2012, 33 patients affected by extracranial germ cell
      tumors and treated according to TGM95 protocol established by the SFOPin a
      pediatric Tunisian oncologic unit. Results Patients had a mean age of 57 months
      (ranges: 1 day-13 years). There were 19 girls and 14 boys. Primary sites included
      12 sacrococcygeal, 11 ovarian, 6 testicular, 3retro peritoneal and 1 mediastinal
      site. After a mean follow up of 26.1 months (ranges: 0-96 months), OSat 2 years
      and 5 years were respectively 82% and 75%. Event-free survival were respectively
      79% at 2 years and 74% at 5 years. Various prognostic factors have been studied
      according to Kaplan-Meier. Univariate analyses identified significant factors
      which influence strongly OS: the stage (p=0.04), the completeness of surgery
      (p<0.001) and the relapse (p = 0, 0001). A multivariate study showed that only
      the quality of resection and the clinical stage remained strong significant
      prognostic factors (p=0,021) for 5-year OS. Conclusion Disease stage,
      completeness of surgery and relapse have been established as the most powerful
      prognostic parameter in our analysis. The improvement of survival of patients
      affected by extracranial germ cell tumors in Tunisia is a real achievement mainly
      due to the success of salvage treatments.

PMID- 27704517
TI  - Contribution of verbal autopsy in the study of cancer mortality among
      reproductive-age women in Tunisia.
AB  - Background In Tunisia, the information system on medical causes of death  is
      based on the use of standard death certificate model based on international model
      recommended by the World Organization started in January 2001. However, this
      system is still burdened with a major death causes of under-registration. Only
      specific surveys on mortality have FAR generate reliable mortality indicators.
      Objectives to study the use of verbal autopsy in order to assess cancer mortality
      among Tunisian women in reproductive age (WRA) . Methods A retrospective  
      national RAMOS survey (Reproductive Age Mortality Study). This survey was
      conducted in 2010 and included all deaths of women aged 15-49 years which
      occurred in 2008 and were due to cancer. Data were collected from civil status
      records and information gathered from families and from health institution's
      registers. For all deaths of women aged 15-49 years, the detailed circumstances
      and the sequence of events leading to death were grouped on a folder called
      "clinical record of verbal autopsy" .Then; all folders were submitted to the
      independent expert. Results During the study period, 1729 deaths among women of
      reproductive age (WRA) were the subject of a verbal autopsy against only 708
      recorded by the National death information system (NDIS). Cancer is the leading
      cause of death among WRA .The specific rate of cancer mortality is 17.83 per 100
      000 WRA against only 7.91 per 100 000 WRA estimated by the NDIS. Breast cancer is
      the leading cause with 35% of all cancers and specific death rate of 6.3 per
      100,000 WRA against 2.48 per 100,000 WRA recorded by the NDIS. Conclusion Verbal
      autopsies Verbal autopsy remains an interesting method for measuring cancer
      mortality in women of a reproductive age especially in countries with a defective
      national death information system.

PMID- 27704518
TI  - Primary immunodeficiencies : Report of 33 Pediatric Tunisian cases.
AB  - Background Primary immunodeficiencies (PID) are a group of heterogeneous and
      relatively rare diseases. Aim to determine the clinical characteristics, outcome
      and genetic data of primary immunodeficiencies in pediatrics patients. Methods A
      retrospective, descriptive and multicentered study, enrolling 33 children
      presenting a PID in Tunis, during a period of 22 years (1991-2012). Resultats a
      masculine predominance has been noticed with a sex ratio at 2,3. Consanguinity
      was found in 71% of family cases. History of early infant deaths was found in 42%
      of cases. The media age of diagnosis was of 1 year 2 months. The median diagnosis
      delay was of 11 months and 1/2. Most frenquently observed PID were combined
      immunodeficiency (36%), mostly severe combined immunodeficiency (SCID) (21%),
      followed by congenial defects of phagocyte function (33%), mostly chronic
      granulomatosis disease (21%). Antibody defects were found in 21% of cases. Most
      frequently observed out comes were lung infections (66%) recurrent oral thrush
      (57%) and diarrhea (42%). Most important complications were severe infections and
      bronchiectasis. 30% of patients were dead by the end of the study. A molecular
      characterization was performed in 33% of patients, and an antenatal diagnosis was
      performed in 10% of cases. Conclusion The PID are a group of disease with
      variable expressions and etiologies. Their frequency remains understimated in
      Tunisia, and their management, difficult and insufficient. We suggest the
      establishment of systematic genetic consulting visit, the creation of a national
      registry and developing bone marrow transplantation in children in Tunisia.

PMID- 27704519
TI  - Exertional heat stroke: about 4 cases.
AB  - Exertional heat stroke is defined as hyperthermia associated with neurological
      signs related to intense physical activity performed in a hot environment. This
      is a medical emergency and life-threatening. In this study, we investigated four
      cases of exertional heat stroke hospitalized at the military hospital in Tunis
      (Tunisia) to describe the clinical, therapeutic and preventive characteristics
      and factors favoring this disease. Four young soldiers, 23 to 44 years older,
      have developed Exertional heat stroke after Intense and prolonged exercise.
      Exercises were performed in May and June, in high ambient temperature, high
      humidity and lack of wind. Three soldiers were in battle dress, a backpack and
      their weapon. Our four subjects had overweight, were not sufficiently trained and
      were highly motivated. Insufficient hydration and a diet rich in carbohydrates
      were noted. Upon hospitalization, patients were febrile and had neurological
      disorders, neuromuscular disorders, rhabdomyolysis and hemoconcentration. The
      medical care consisted of a rehydration and oxygen.

PMID- 27704521
TI  - Myofibroblastoma of the breast: Report of an exceptional case occurring in a
      young girl.

PMID- 27704520
TI  - The emergent use of Cardiopulmonary bypass and extracorporeal membrane oxygenator
      in a child with sickle cell disease.
AB  - The use of Cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenator
      (ECMO) in patients suffering from Sickle cell disease (SCD) needs specific
      precautions. Whereas, no consensual protocols have been established to clarify
      therapeutic management. CASE REPORT A 7-year-old boy was admitted to the hospital
      for surgery of advanced endocarditis.  Major dyspnea, hemodynamic distress and
      fever were noted on physical examination. Biological tests exploring anaemia
      revealed Haemoglobin (Hb) S levels of 39.1%. Echocardiography showed important
      right heart cavities dilation with multiple aortic vegetations. The child was
      accepted for emergent surgery. Ten minutes after anesthetic induction, serious
      hemodynamic distress was established. The patient was put on normothermic CPB
      when he received four packed red-blood-cell. After surgery, he was placed on ECMO
      support for 2 days than he succumbed. CONCLUSION Urgent cardiac surgery in
      patients suffering from SCD poses a major therapeutic dilemma. Multiplying case
      reports and encouraging prospective studies are necessary to define the right
      place of cardio-pulmonary assistance in treatment protocols for better
      management.

PMID- 27704522
TI  - Gliosarcoma with smooth muscle cell differentiation: a case report.

PMID- 27704523
TI  - The effect of bilberries on diabetes-related alterations of interstitial cells of
      Cajal in the lower oesophageal sphincter in rats.
AB  - Diabetic gastroenteropathy involves not only the parasympathetic and sympathetic
      autonomic nerves, but also enteric neurons, smooth muscle cells and interstitial
      cells of Cajal (ICC). ICC are the cells of mesenchymal origin that occur within
      and around the muscle layers in the gastrointestinal tract. The objective of the
      present study was to investigate the alterations of ICC in the lower oesophageal
      sphincter (LOS) of streptozotocin-nicotinamide non-insulin-dependent diabetes
      rats. Moreover, we investigated possible ICC in rats with the same type of
      diabetes, treated with bilberry fruit extract, bearing in mind that its
      hypoglycemic effect had been already proven. Male Wistar rats (10 weeks old) were
      used, and diabetes was induced by an intraperitoneal injection of streptozotocin,
      immediately after intraperitoneal application of nicotinamide. The specimens were
      exposed to anti-c-kit antibodies to investigate the distribution of ICC, and the
      smooth muscle cells were immunohistochemically labelled using anti-desmin
      antibodies. Intramuscular ICC were very abundant in the LOS of rats. They were
      spindle-shaped, with two long processes connecting them into long linear
      sequences. In the LOS of diabetic rats, intramuscular ICC were rarely present and
      linear cell-cell connections between these cells were completely missing. In
      groups treated with bilberry, the number and distribution of ICC were exactly the
      same as in the above described rats with induced diabetes. In summary, a decrease
      of intramuscular ICC, discontinuities and breakdown of contacts between ICC were
      observed in streptozotocin-nicotinamide induced diabetes rats and in groups
      treated with bilberry. Bilberry fruit extract was shown to have hypoglycemic
      activity, but without any protective effects on ICC in the LOS of diabetic rats.

PMID- 27704524
TI  - Do leprosy and tuberculosis generate a systemic inflammatory shift? Setting the
      ground for a new dialogue between experimental immunology and bioarchaeology.
AB  - : It is possible that during long lasting chronic infections such as tuberculosis
      (TB) and leprosy individuals who generate a stronger immune response will produce
      a chronic shift in the systemic levels of inflammatory proteins. Consequently,
      the systemic immunological shift could affect inflammatory responses against
      other persistent pathogens such as Porphyromonas gingivalis associated with
      periodontal disease (PD). OBJECTIVE: To determine if in vitro exposure to
      Mycobacterium tuberculosis or M. leprae lysates impacts subsequent immune
      responses to P. gingivalis; and to propose a new dialogue between experimental
      immunology and paleopathology. MATERIAL AND METHODS: We sequentially (2 days
      protocol) exposed peripheral blood mononuclear cells (PBMCs) from healthy donors
      to bacterial lysates either from M. tuberculosis, or M. leprae, or P. gingivalis.
      After collecting all supernatants, we measured the expression of immune proteins
      TNFalpha and IFNgamma using an enzyme-linked immunosorbent assay. RESULTS: Early
      exposure (day 1) of PBMCs to M. leprae or M. tuberculosis lysates induces an
      inflammatory shift detected by the increase of TNFalpha and IFNgamma when the
      same cells are subsequently (day 2) exposed to oral pathogen P. gingivalis.
      DISCUSSION: By extrapolating these results, we suggest that chronic infections,
      such as TB and leprosy, could generate a systemic immunological shift that can
      affect other inflammatory processes such the one present in PD. We propose that
      the presence and severity of PD should be explored as a proxy for inflammatory
      status or competence when reconstructing the health profile in past populations.

PMID- 27704525
TI  - Declining Amenable Mortality: Time Trend (2000-2013) and Geographic Area
      Analysis.
AB  - OBJECTIVE: To update amenable mortality in 32 OECD countries at 2013 (or last
      available year), to describe the time trends during 2000-2013, and to evaluate
      the association of these trends with various geographic areas. DATA SOURCES:
      Secondary data from 32 countries during 2000-2013, gathered from the World Health
      Organization Mortality Database. STUDY DESIGN: Time trend analysis. DATA
      COLLECTION: Using Nolte and McKee's list, age-standardized amenable mortality
      rates (SDRs) were calculated as the annual number of deaths over the population
      aged 0-74 years per 100,000 inhabitants. We performed a mixed-effects polynomial
      regression analysis on the annual SDRs to determine whether specific geographic
      areas were associated with different SDR trajectories over time. PRINCIPAL
      FINDINGS: The OECD average annual decrease was 3.6/100,000 (p < .001), but slowed
      over time (coefficient for the quadratic term = 0.11, p < .001). Eastern and
      Atlantic European countries had the steepest decline (-6.1 and -4.7,
      respectively), while Latin American countries had the lowest slope (-1.7). The
      OECD average annual decline during the 14-year period was -0.5 (p < .001) for
      cancers and -2.5 (p < .001) for cardiovascular diseases, with significant
      differences among countries. CONCLUSION: Declining trend of amenable SDRs was
      continuing to 2013 but with steepness change compared with previous periods and
      with a slowdown.

PMID- 27704526
TI  - Integrating feeding behavior, ecological data, and DNA barcoding to identify
      developmental differences in invertebrate foraging strategies in wild white-faced
      capuchins (Cebus capucinus).
AB  - OBJECTIVES: Invertebrate foraging strategies in nonhuman primates often require
      complex extractive foraging or prey detection techniques. As these skills take
      time to master, juveniles may have reduced foraging efficiency or concentrate
      their foraging efforts on easier to acquire prey than adults. MATERIALS AND
      METHODS: We use DNA barcoding, behavioral observations, and ecological data to
      assess age-based differences in invertebrate prey foraging strategies in a group
      of white-faced capuchins (Cebus capucinus) in northeastern Costa Rica.
      Invertebrate availability was monitored using canopy traps and sweep netting.
      Fecal samples were collected from adult female, adult male, and juvenile white
      faced capuchins (n = 225). COI mtDNA sequences were compared with known sequences
      in GenBank and the Barcode of Life Database. RESULTS: Frequencies of Lepidoptera
      and Hymenoptera consumption were higher in juveniles than in adults. A
      significantly smaller proportion of juvenile fecal samples contained Gryllidae
      and Cercopidae sequences, compared with adults (0% and 4.2% vs. 4.6% and 12.5%),
      and a significantly larger proportion contained Tenthredinidae, Culicidae, and
      Crambidae (5.6%, 9.7%, and 5.6% vs. 1.3%, 0.7%, and 1.3%). Juveniles spent
      significantly more time feeding and foraging than adults, and focused their
      foraging efforts on prey that require different skills to capture or extract.
      Arthropod availability was not correlated with foraging efficiency, and the rate
      of consumption of specific orders of invertebrates was not correlated with the
      availability of those same taxa. DISCUSSION: Our data support the hypothesis that
      juveniles are concentrating their foraging efforts on different prey than adults,
      potentially focusing their foraging efforts on more easily acquired types of
      prey.

PMID- 27704527
TI  - Cardiovascular risk prevention and all-cause mortality in primary care patients
      with an abdominal aortic aneurysm.
AB  - BACKGROUND: Perioperative mortality is low for patients undergoing abdominal
      aortic aneurysm (AAA) repair, but long-term survival remains poor. Although
      patients diagnosed with AAA have a significant burden of cardiovascular disease
      and associated risk factors, there is limited understanding of the contribution
      of cardiovascular risk management to long-term survival. METHODS: General
      practice records within The Health Improvement Network (THIN) were examined.
      Patients with a diagnosis of AAA and at least 1 year of registered medical
      history were identified from 2000 to 2012. Medical therapies for cardiovascular
      risk were classified as antiplatelet, statin or antihypertensive agents.
      Progression to death was investigated using the G-computation formula with time
      dependent co-variables to account for differences in exposure to cardiovascular
      risk-modifying treatments and the confounding between exposure, co-morbidities
      and death. RESULTS: Some 12 485 patients had a recorded diagnosis of AAA. From
      2000 to 2012, prescription of medications that modify cardiovascular risk
      increased: from 26.6 to 76.7 per cent for statins, from 56.5 to 73.9 per cent for
      antiplatelet agents and from 75.3 to 84.0 per cent for antihypertensive drugs.
      Adjusted Kaplan-Meier curves demonstrated a better 5-year survival rate in
      patients receiving statins (68.4 versus 42.2 per cent), antiplatelet agents (63.6
      versus 39.7 per cent) or antihypertensive agents (61.5 versus 39.1 per cent),
      compared with rates in patients not receiving each therapy. CONCLUSION:
      Appropriate risk factor modification could significantly reduce long-term
      mortality in patients with AAA. In the UK, up to 30 per cent of patients are not
      currently receiving these medications.

PMID- 27704529
TI  - An adaptive Mantel-Haenszel test for sensitivity analysis in observational
      studies.
AB  - In a sensitivity analysis in an observational study with a binary outcome, is it
      better to use all of the data or to focus on subgroups that are expected to
      experience the largest treatment effects? The answer depends on features of the
      data that may be difficult to anticipate, a trade-off between unknown effect
      sizes and known sample sizes. We propose a sensitivity analysis for an adaptive
      test similar to the Mantel-Haenszel test. The adaptive test performs two highly
      correlated analyses, one focused analysis using a subgroup, one combined analysis
      using all of the data, correcting for multiple testing using the joint
      distribution of the two test statistics. Because the two component tests are
      highly correlated, this correction for multiple testing is small compared with,
      for instance, the Bonferroni inequality. The test has the maximum design
      sensitivity of two component tests. A simulation evaluates the power of a
      sensitivity analysis using the adaptive test. Two examples are presented. An R
      package, sensitivity2x2xk, implements the procedure.

PMID- 27704528
TI  - A joint modeling approach for multivariate survival data with random length.
AB  - In many biomedical studies that involve correlated data, an outcome is often
      repeatedly measured for each individual subject along with the number of these
      measurements, which is also treated as an observed outcome. This type of data has
      been referred as multivariate random length data by Barnhart and Sampson (1995).
      A common approach to handling such type of data is to jointly model the multiple
      measurements and the random length. In previous literature, a key assumption is
      the multivariate normality for the multiple measurements. Motivated by a
      reproductive study, we propose a new copula-based joint model which relaxes the
      normality assumption. Specifically, we adopt the Clayton-Oakes model for multiple
      measurements with flexible marginal distributions specified as semi-parametric
      transformation models. The random length is modeled via a generalized linear
      model. We develop an approximate EM algorithm to derive parameter estimators and
      standard errors of the estimators are obtained through bootstrapping procedures
      and the finite-sample performance of the proposed method is investigated using
      simulation studies. We apply our method to the Mount Sinai Study of Women Office
      Workers (MSSWOW), where women were prospectively followed for 1 year for studying
      fertility.

PMID- 27704530
TI  - Early outcomes from the Dutch Upper Gastrointestinal Cancer Audit.
AB  - BACKGROUND: In 2011, the Dutch Upper Gastrointestinal Cancer Audit (DUCA) group
      began nationwide registration of all patients undergoing surgery with the
      intention of resection for oesophageal or gastric cancer. The aim of this study
      was to describe the initiation and implementation of this process along with an
      overview of the results. METHODS: The DUCA is part of the Dutch Institute for
      Clinical Auditing. The audit provides (surgical) teams with reliable, weekly
      updated, benchmarked information on process and (case mix-adjusted) outcome
      measures. To accomplish this, a web-based registration was designed, based on a
      set of predefined quality measures. RESULTS: Between 2011 and 2014, a total of
      2786 patients with oesophageal cancer and 1887 with gastric cancer were
      registered. Case ascertainment approached 100 per cent for patients registered in
      2013. The percentage of patients with oesophageal cancer starting treatment
      within 5 weeks of diagnosis increased significantly over time from 32.5 per cent
      in 2011 to 41.0 per cent in 2014 (P < 0.001). The percentage of patients with a
      minimum of 15 examined lymph nodes in the resected specimen also increased
      significantly for both oesophageal cancer (from 50.3 per cent in 2011 to 73.0 per
      cent in 2014; P < 0.001) and gastric cancer (from 47.5 per cent in 2011 to 73.6
      per cent in 2014; P < 0.001). Postoperative mortality remained stable (around 4.0
      per cent) for patients with oesophageal cancer, and decreased for patients with
      gastric cancer (from 8.0 per cent in 2011 to 4.0 per cent in 2014; P = 0.031).
      CONCLUSION: Nationwide implementation of the DUCA has been successful. The
      results indicate a positive trend for various process and outcome measures.

PMID- 27704532
TI  - Physical activity and depression: a large cross-sectional, population-based study
      across 36 low- and middle-income countries.
AB  - OBJECTIVE: Physical activity (PA) is good for health, yet several small-scale
      studies have suggested that depression is associated with low PA. A paucity of
      nationally representative studies investigating this relationship exists,
      particularly in low- and middle-income countries (LMICs). This study explored the
      global association of PA with depression and its mediating factors. METHOD:
      Participants from 36 LMICs from the World Health Survey were included.
      Multivariable logistic regression analyses were undertaken exploring the
      relationship between PA and depression. RESULTS: Across 178 867 people (mean +/-
      SD age = 36.2 +/- 13.5 years; 49.9% male), the prevalence of depression and the
      prevalence of low PA were 6.6% and 16.8% respectively. The prevalence of low PA
      was significantly higher among those with depression vs. no depression (26.0% vs.
      15.8%, P < 0.0001). In the adjusted model, depression was associated with higher
      odds for low PA (OR = 1.42; 95% CI = 1.24-1.63). Mediation analyses demonstrated
      that low PA among people with depression was explained by mobility limitations
      (40.3%), pain and discomfort (35.8%), disruptions in sleep and energy (25.2%),
      cognition (19.4%) and vision (10.9%). CONCLUSION: Individuals with depression
      engage in lower levels of PA in LMICs. Future longitudinal research is warranted
      to better understand the relationships observed.

PMID- 27704531
TI  - Greedy outcome weighted tree learning of optimal personalized treatment rules.
AB  - We propose a subgroup identification approach for inferring optimal and
      interpretable personalized treatment rules with high-dimensional covariates. Our
      approach is based on a two-step greedy tree algorithm to pursue signals in a high
      dimensional space. In the first step, we transform the treatment selection
      problem into a weighted classification problem that can utilize tree-based
      methods. In the second step, we adopt a newly proposed tree-based method, known
      as reinforcement learning trees, to detect features involved in the optimal
      treatment rules and to construct binary splitting rules. The method is further
      extended to right censored survival data by using the accelerated failure time
      model and introducing double weighting to the classification trees. The
      performance of the proposed method is demonstrated via simulation studies, as
      well as analyses of the Cancer Cell Line Encyclopedia (CCLE) data and the
      Tamoxifen breast cancer data.

PMID- 27704533
TI  - Perimortem caesarean section: Two cases performed in New Zealand hospitals.
AB  - Perimortem caesarean section is a term many obstetricians are familiar with
      despite few encountering it first-hand. It is estimated the intervention will be
      needed every 53 000 maternities. Despite this rarity it is vital clinicians are
      trained in detecting and intervening where perimortem caesarean is required. In
      New Zealand eight perimortem caesareans were performed from 2006 to 2013. Here we
      discuss two perimortem caesarean sections performed in two New Zealand hospitals
      alongside current guidance and recommendations.

PMID- 27704534
TI  - The Longitudinal Course of Pain and Analgesic Therapy Following Aneurysmal
      Subarachnoid Hemorrhage: A Cohort Study.
AB  - OBJECTIVE: The purpose of this study was to determine the duration, intensity,
      location, and usual treatment of pain throughout hospitalization following
      subarachnoid hemorrhage. BACKGROUND: Headache following subarachnoid hemorrhage
      can be sudden and severe. Little is known about the longitudinal course of
      headache or its analgesic therapy following the initial diagnosis of subarachnoid
      hemorrhage. METHODS: A prospectively maintained database of 564 patients
      diagnosed with cerebral aneurysms collected from 10/2009 to 2/2013 was searched
      for conscious patients with subarachnoid hemorrhage. Available electronic records
      were queried for pain scores (0-10/10), location, and analgesic consumption.
      RESULTS: Forty-six adults with subarachnoid hemorrhage met eligibility criteria
      for inclusion. Mean [CI 95] daily pain was 3.8 [3.2, 4.4] and maximal daily pain
      was 5.8 [5.1, 6.6]. Eighty-nine percent of patients reported severe pain of 7
      10/10, and 63% of patients reported 10/10 pain at some point during
      hospitalization. While mean [CI 95] pain declined over the course of hospital
      stay at a rate of 0.06 [0.04, 0.07] units/day (P < .001), mean [CI 95] maximal
      daily pain changed at a rate of -0.03 [-0.06, 0.01] units/day, which is not
      significantly different than zero (P = .15). Pain was located primarily in the
      head in 76% of subjects but pain in the back, neck, limbs, and eyes was also
      reported. All patients received oral acetaminophen with increasing daily doses.
      All but three patients, received opioids, most commonly intravenous fentanyl and
      oral oxycodone. The mean [95 CI] intravenous morphine equivalent dose of opioids
      consumed was 15.7 [10.3, 21.1] mg/day and changed at a rate of -0.11 [-0.37,
      0.15] mg/day which is not significantly different than zero (P = .40).
      CONCLUSION: Despite steady consumption of analgesics, the pain reported by
      conscious patients while recovering from subarachnoid hemorrhage in the hospital
      is often severe and persists throughout hospitalization.

PMID- 27704535
TI  - The association between pre-operative variables, including blood pressure, and
      postoperative kidney function.
AB  - We used multivariate analyses to assess the association of pre-operative
      variables with kidney function in 41,523 adults after scheduled surgery in a
      single large academic hospital. Eight variables were independently associated
      with a reduction in postoperative estimated glomerular filtration rate: pre
      operative renal function; age; ASA physical status; cardiac failure; anaemia;
      cancer; type of surgery; and the lowest quartile of pre-operative mean arterial
      blood pressure (< 71 mmHg). The estimated glomerular filtration rate fell by a
      mean (95% CI) of 2.7 (0.04-5.40) ml.min-1 .1.73 m-2 for patients with a pre
      operative mean arterial pressure < 71 mmHg, p = 0.047. The same variables and
      male sex were associated with postoperative acute kidney injury. The odds ratio
      (95% CI) for acute postoperative kidney injury was 1.9 (1.2-2.9) for patients
      with a pre-operative mean arterial blood pressure < 71 mmHg, p = 0.005.

PMID- 27704536
TI  - A Neanderthal deciduous human molar with incipient carious infection from the
      Middle Palaeolithic De Nadale cave, Italy.
AB  - OBJECTIVES: The aim of the study is the assessment of Nadale 1, a Neanderthal
      deciduous tooth recently discovered in Northeastern Italy in the De Nadale cave
      (Middle Palaeolithic). Together with the clear archaeological context of the
      site, this study brings new insight on Neanderthal behavior and dental
      morphological variability. MATERIALS AND METHODS: We used microCT data to provide
      a morphological description and morphometric analysis (diameter measurements and
      dental tissue volumes) of the Nadale 1 human tooth. Microwear analysis,
      taphonomical investigation and caries identification were performed using a
      stereomicroscope and Scanning Electron Microscope. RESULTS: In terms of
      morphology (i.e., incipient tuberculum molare, marked mesial marginal ridge and
      well-developed mid-trigonid crest connecting the protoconid and the metaconid,
      deep anterior fovea) and size, Nadale 1 presents features frequently observed in
      Neanderthal lower first deciduous molars. Microscope investigations reveal the
      presence of a small pit which could be correlated to an incipient caries.
      CONCLUSION: Nadale 1 expands the Italian Middle Palaeolithic fossil record and
      provides further information on Neanderthal dm1s in terms of dimensional and
      morphological variability. Furthermore, the presence of an incipient caries
      brings further data on Neanderthal diet.

PMID- 27704537
TI  - Systematic review of the prevalence of faecal incontinence.
AB  - BACKGROUND: Faecal incontinence (FI) is widely recognized as a significant
      problem in the community. Conjecture exists around the proportion of the
      population affected. This systematic review evaluated studies reporting the
      community prevalence of FI in terms of methodology, design and definitions.
      METHODS: MEDLINE, Embase, CINAHL, the Cochrane Collaboration and National
      Guideline databases were searched for studies investigating the prevalence of FI
      in community-based adults published from January 1966 to February 2015. Study
      data, including methodology, sample size, response rate, definition of FI and
      prevalence rates, were extracted on to a pro forma and appraised critically.
      Where possible, FI prevalence estimates were pooled. RESULTS: Thirty studies were
      analysed from 4840 screened articles. FI prevalence estimates varied from 1.4 to
      19.5 per cent. This variation was explained by differences in data collection
      method and two factors within definitions of FI: type of stool and frequency of
      FI episodes. When these factors were accounted for, the FI prevalence at a
      threshold of at least once per month for liquid or solid stool was 8.3-8.4 per
      cent for face-to-face or telephone interviews, and 11.2-12.4 per cent for postal
      surveys. The pooled prevalence rate from studies for functional FI (defined by
      ROME II criteria) was 5.9 (95 per cent c.i. 5.6 to 6.3) per cent. CONCLUSION:
      When comparable methodologies and definitions are used, studies produce
      remarkably similar prevalence rates in different community populations. FI
      remains an unspoken symptom, with lower rates reported in personal interviews
      compared with anonymous postal questionnaires.

PMID- 27704538
TI  - Presenting a New, Non-Hormonally Mediated Cyclic Headache in Women: End-Menstrual
      Migraine.
AB  - BACKGROUND: This retrospective observational study describes what appears to be a
      not-uncommon yet not previously typified headache disorder, "end-menstrual
      migraine" (EMM) named for its proximate occurrence with the terminal days of
      menstrual bleeding each month. METHODS: Our menstrual migraine (MM) clinic's
      database was queried for patients with migraine, regular menses, and the locally
      used diagnostic code of EMM, signifying the patient's assertion that she had
      migraine at the end of menses as well as calendar data confirming that
      association. Serum ferritin levels were available for all subjects with EMM.
      RESULTS: Among the most recently seen 119 women in the clinic, 85 had both
      regular menses and a diagnosis of migraine, and were thus appropriate for
      evaluation. In this selected population, 30 women (35.3%) were confirmed to have
      EMM. Twenty-eight of those 30 patients (93.3%) had ferritin levels that fell
      below the generally accepted lower desirable limit of 50 ng/mL (mean = 21.9
      ng/mL) - half of whom fell below 18 ng/mL, the established minimum levels for
      women. CONCLUSIONS: EMM is a common complaint in women evaluated for menstrual
      related migraine (MRM), yet these migraines occur many days after the estrogen
      withdrawal that precipitates MRM. The authors do not believe that EMM is
      hormonally mediated, but rather that it is causally related to menstrual blood
      loss, resulting in a brief relative anemia with consequent migraine. Further
      study is needed to substantiate this association, search for confounders, and
      evaluate response to iron therapy.

PMID- 27704540
TI  - Antenatal pertussis vaccination: Are we implementing best evidence into practice?
AB  - Maternal immunisation is the most effective strategy to reduce infant morbidity
      and mortality from pertussis infection, and is now standard of care in many
      countries, including Australia. However, uptake cannot be guaranteed unless the
      barriers to implementing programs locally are understood. Education and resources
      for antenatal care providers, embedding vaccination within antenatal care, and
      provision of culturally appropriate information for pregnant women are integral
      to a successful antenatal vaccination program.

PMID- 27704539
TI  - Poison frog color morphs express assortative mate preferences in allopatry but
      not sympatry.
AB  - The concurrent divergence of mating traits and preferences is necessary for the
      evolution of reproductive isolation via sexual selection, and such coevolution
      has been demonstrated in diverse lineages. However, the extent to which
      assortative mate preferences are sufficient to drive reproductive isolation in
      nature is less clear. Natural contact zones between lineages divergent in traits
      and preferences provide exceptional opportunities for testing the predicted
      evolutionary consequences of such divergence. The strawberry poison frog (Oophaga
      pumilio) displays extreme color polymorphism in and around the young Bocas del
      Toro archipelago. In a transition zone between red and blue allopatric lineages,
      we asked whether female preferences diverged along with coloration, and whether
      any divergent preferences persist in a zone of sympatry. When choosing among red,
      blue and phenotypically intermediate males, females from monomorphic red and
      monomorphic blue populations both expressed assortative preferences. However,
      red, blue, and intermediate females from the contact zone all preferred red
      males, suggesting that divergent preferences may be insufficient to effect
      behavioral isolation. Our results highlight the complexity of behavioral
      isolation, and the need for studies that can reveal the circumstances under which
      divergent preferences do and do not contribute to speciation.

PMID- 27704541
TI  - User characteristics, experiences and continuation rates of copper intrauterine
      device use in a cohort of Australian women.
AB  - BACKGROUND: Copper intrauterine device (Cu-IUD) use in Australia is low despite
      being a highly effective, cost effective non-hormonal contraceptive with reported
      12-month continuation rates of 85% compared to 59% for oral contraception. AIMS:
      To describe the characteristics of Cu-IUD users in the Australian context, their
      experiences of side effects, continuation rates and reasons for discontinuation.
      METHODS: Between August 2009 and January 2012 we undertook a prospective cohort
      study of consecutive women presenting for Cu-IUD insertion to three family
      planning clinics in Queensland and New South Wales. We used survival analysis for
      continuation rates and univariate and multivariable analyses to characterise
      users, their experiences up to three years and reasons for discontinuation.
      RESULTS: Of the 211 enrolled women, a third (36.0%) were aged under 30 and a
      third were nulliparous (36.5%). Efficacy and lack of hormones were the most
      frequently cited reasons to choose the method. Four women were lost to follow-up.
      Overall continuation rates were 79.1% at one year and 61.3% at three years. Early
      discontinuation was reduced in those with two or more children (adjusted hazards
      ratio 0.22, 95% CI 0.09-0.50). Heavy menstrual bleeding was the commonest reason
      for removal in 28 of 59 (47.5%) discontinuations due to complications or side
      effects. One uterine perforation and one method failure resulting in an ectopic
      pregnancy occurred. CONCLUSIONS: Cu-IUDs were chosen for their efficacy and lack
      of hormones by a range of Australian women, including young and nulliparous
      women. While bleeding-related side effects were relatively common, overall
      continuation rates were high. Serious complications and failures were rare.

PMID- 27704543
TI  - Rehabilitative and therapeutic neuroarchitecture.

PMID- 27704542
TI  - Contextual organismality: Beyond pattern to process in the emergence of
      organisms.
AB  - Biologists have taken the concept of organism largely for granted. However,
      advances in the study of chimerism, symbiosis, bacterial-eukaryote associations,
      and microbial behavior have prompted a redefinition of organisms as biological
      entities exhibiting low conflict and high cooperation among their parts. This
      expanded view identifies organisms in evolutionary time. However, the ecological
      processes, mechanisms, and traits that drive the formation of organisms remain
      poorly understood. Recognizing that organismality can be context dependent, we
      advocate elucidating the ecological contexts under which entities do or do not
      act as organisms. Here we develop a "contextual organismality" framework and
      provide examples of entities, such as honey bee colonies, tumors, and bacterial
      swarms, that can act as organisms under specific life history, resource, or other
      ecological circumstances. We suggest that context dependence may be a stepping
      stone to the development of increased organismal unification, as the most
      integrated biological entities generally show little context dependence.
      Recognizing that organismality is contextual can identify common patterns and
      testable hypotheses across different entities. The contextual organismality
      framework can illuminate timeless as well as pressing issues in biology,
      including topics as disparate as cancer emergence, genomic conflict, evolution of
      symbiosis, and the role of the microbiota in impacting host phenotype.

PMID- 27704544
TI  - Mindfulness training for loneliness among Chinese college students: A pilot
      randomized controlled trial.
AB  - Loneliness has been found to predict a wide range of physical and mental health
      problems. It is suggested that China's One-Child Policy places young Chinese
      people at a particularly high risk for loneliness. Although loneliness is most
      prevalent in late adolescence and early adulthood, interventions have primarily
      targeted children or older adults with limited success. The current study
      examines a pilot randomized controlled trial of a mindfulness training program
      among Chinese college students. Participants with elevated loneliness (N = 50,
      ages 17-25) were randomized into either an 8-week mindfulness training or a
      control group. Self-reported measures of loneliness and mindfulness were
      administered at baseline and posttest. The training group also completed a
      program evaluation form and a 3-month follow-up assessment. Results provided
      preliminary evidence indicating that the intervention was feasible and effective
      at reducing loneliness among Chinese college students. Limitations and future
      directions were discussed.

PMID- 27704545
TI  - Effect of two doses of urea foliar application on leaves and grape nitrogen
      composition during two vintages.
AB  - BACKGROUND: Nitrogen affects grapevine growth and also yeast metabolism, which
      have a direct influence on fermentation kinetics and the formation of different
      volatile compounds. Throughout the grapevine cycle, soil nitrogen availability
      and grape nitrogen composition can vary because of different factors. Nitrogen
      foliar applications can contribute toward enhancing grapevine nitrogen status and
      minimize the problem of leaching that traditional nitrogen-soil applications can
      provoke. The present study aimed to evaluate the influence of urea foliar
      applications on grapevine nitrogen status and grape amino acid content.
      Accordingly, two different doses of urea were applied over the leaves of a
      'Tempranillo' vineyard. RESULTS: The highest urea doses affected nitrogen content
      on blade leaf tissues after veraison. Must amino acid profiles were modified by
      urea application and some of the compounds increased their concentrations. The
      effect of year on the increase of must total amino acid concentrations was more
      important than the effect of the doses applied. CONCLUSION: Urea foliar
      applications can be an interesting tool for decreasing grapevine nitrogen
      deficiencies. This method of nitrogen implementation in the vineyard could avoid
      sluggish fermentation problems during winemaking, enhance must nitrogen
      composition, and contribute to improving wine quality. (c) 2016 Society of
      Chemical Industry.

PMID- 27704546
TI  - Programming a randomized dependent group contingency and common stimuli to
      promote durable behavior change.
AB  - Low levels of academic engagement may impede students' acquisition of skills.
      Intervening on student behavior using group contingencies may be a feasible way
      to increase academic engagement during group instruction. The current study
      examined the effect of a randomized dependent group contingency on levels of
      academic engagement for second-grade participants receiving small-group reading
      and writing instruction. The results showed that a randomized dependent group
      contingency increased the academic engagement of primary participants and several
      of the other participants during small-group instruction. The findings also
      showed that high levels of academic engagement were maintained when common
      stimuli were present and the dependent group contingency was withdrawn.

PMID- 27704547
TI  - Cognitive Orientation to daily Occupational Performance (CO-OP) as group therapy
      for children living with motor coordination difficulties: An integrated
      literature review.
AB  - BACKGROUND/AIM: Children with Developmental Coordination Disorder (DCD)
      demonstrate limited participation in daily occupations which negatively impacts
      their physical and psycho-social wellbeing. The CO-OP approach is strongly
      supported within the literature as an effective treatment for DCD when delivered
      as a one-on-one therapy. Group interventions have proven to be effective in
      increasing self-esteem, decreasing feelings of isolation and are a cost effective
      way of delivering therapy. The purpose of this review was to explore the evidence
      for the use of the CO-OP approach in a group format for children with motor
      coordination difficulties. METHODS: Searches of CINAHL, MEDLINE, Scopus,
      Proquest, PsycINFO, ERIC and OTDBase, were conducted from 2000 through until
      September 30, 2015. Articles included were in English, peer reviewed articles,
      followed principals of CO-OP and were delivered through a group therapy approach.
      All articles were critically reviewed and thematically analysed. RESULTS: 192
      studies were retrieved with a final number of six articles included in the
      review. Six themes were highlighted: achieving a new level of perceived
      competence; feeling a sense of belonging; children learning how the condition
      affected them and strategies to overcome these challenges; careful formation of
      intervention groups; the value of following the CO-OP protocols; and the
      significance of parental involvement. CONCLUSION: The findings of this review
      suggest that the CO-OP approach, when administered in a group format, has the
      potential to benefit children living with motor coordination difficulties in both
      physical and psycho-social domains. More research is required to confirm these
      findings and contribute to evidence-based practice.

PMID- 27704548
TI  - Is job performance independent from career success? A conceptual distinction
      between competence and agency.
AB  - Adopting a social approach to social judgment, we conducted five studies to
      validate a conceptual distinction between agency and competence traits. Studies 1
      3 revealed that competence traits (e.g., skillful) are associated with job
      performance, whereas agentic traits (e.g., ambitious) are associated with career
      success. Study 4 showed that only agency predicted the amount of money people are
      likely to earn: the more a given trait was considered as agentic, the more it was
      associated with high monetary values. Study 5 highlighted the predominance of
      agency traits over competence traits in the evaluation of an employee applying
      for a promotion. Nevertheless, participants asserted that competence was the main
      criterion they used to judge the applicant. Implications of the conceptual
      distinction between agency and competence for social cognition are discussed.

PMID- 27704549
TI  - Acute gastroenteritis outbreak associated to norovirus GI.9 in a Portuguese army
      base.
AB  - Gastroenteritis is considered a major illness within the military settings being
      caused by foodborne enteric pathogens that are particularly easily spread in the
      crowded conditions of military camps. Gastroenteritis outbreaks caused by
      norovirus usually affect a great number of soldiers due to the low infectious
      dose, copious viral shedding, and environmental stability. The present study
      describes the investigation of an outbreak of acute gastroenteritis that occurred
      in April 2015 in a Portuguese army base, focusing on the study of the
      epidemiological curve, symptoms experienced by the affected soldiers, and results
      of food, water, and stool microbiological analysis. From a total of 938 military
      personnel stationed on the base 46 soldiers developed acute gastroenteritis.
      Stool analysis of seven cases showed to be positive for norovirus GI.9 that was
      the probable cause of the outbreak. This report shows that genogroup I norovirus
      can also cause considerable morbidity in healthy young soldiers, affecting the
      operational effectiveness on the military forces. J. Med. Virol. 89:922-925,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27704550
TI  - Recommended strategies for the oral administration of paediatric medicines with
      food and drinks in the context of their biopharmaceutical properties: a review.
AB  - OBJECTIVES: This review focuses on the recommended strategies for the oral
      administration of paediatric medicines with food in the context of their
      biopharmaceutical properties. KEY FINDINGS: Acceptability of oral medicines in
      young patients is more challenging than in adult patients. Mixing oral dosage
      forms with foods and drinks is sometimes suggested to administer a specific dose
      and enhance compliance in the paediatric population. In this review, the
      strategies for the co-administration of paediatric medicines with food and drinks
      are discussed. Current administration practices as reported by healthcare
      professionals and parents/carers are compared with the relevant guidelines.
      Differences in the type of vehicles recommended to be used and actually used in
      current practice were identified. Correlations of the type of food recommended,
      the type of formulation and the drug's biopharmaceutical classification system
      (BCS) class were performed and revealed that recommendations should be made on a
      case-by-case basis. SUMMARY: The propensity for physiochemical or bioavailability
      changes that may occur from the co-administration of medicines with food and
      drinks in the paediatric population should be considered, and harmonisation of
      the recommended administration strategies is needed.

PMID- 27704551
TI  - Challenge of paediatric compounding to solid dosage forms sachets and hard
      capsules - Finnish perspective.
AB  - OBJECTIVES: The study evaluated the quality of compounded sachets and hard
      gelatine capsules and their feasibility in paediatric drug administration.
      METHODS: Commercial tablets were compounded to sachets and capsules in hospital
      environment, and the uniformity of content and simulated drug dose were
      determined. KEY FINDINGS: Compounded formulations were successfully obtained for
      a range of drug substances; dipyridamole, spironolactone, warfarin and sotalol
      formulations were within acceptable limits for uniformity of content, in most
      cases. However, some loss of drug was seen. The type and amount of excipients
      were found to affect uniformity of content; good conformity of capsules was
      obtained using lactose monohydrate as filler, whereas microcrystalline cellulose
      was a better choice in sachets. In capsules, content uniformity was obtained for
      a range of drug doses. If the drug is aimed to be administered through a
      nasogastric tube, solubility of the drug and excipients should be considered, as
      they were found to affect the simulated drug dose in administration. CONCLUSIONS:
      Compounded sachets and capsules fulfilled the quality requirements in most cases.
      In compounding, the choice of excipients should be considered as they can affect
      conformity of the dosage form or its usability in practice. Quality assurance of
      compounded formulations should be taken into consideration in hospital
      pharmacies.

PMID- 27704552
TI  - I am Cait, and I am a transgender blood donor.

PMID- 27704553
TI  - Kelp transcriptomes provide robust support for interfamilial relationships and
      revision of the little known Arthrothamnaceae (Laminariales).
AB  - If ever there were "charismatic megaflora" of the sea, the Laminariales (kelp)
      would undoubtedly meet that designation. From the Northeast Pacific kelp forests
      to the less diverse, but nonetheless dense, kelp beds ranging from the Arctic to
      the cold temperate waters of the Southern Hemisphere, kelp provide habitat
      structure and food for a variety of productive marine systems. Consequently, kelp
      are well represented in the literature, however, understanding their evolution
      has proven challenging. We used a 152-gene phylogenomics approach to better
      resolve the phylogeny of the "derived" kelp families (viz., Agaraceae,
      Alariaceae, Laminariaceae, and Lessoniaceae). The formerly unresolved Egregia
      menziesii firmly joined a significantly expanded Arthrothamnaceae including
      Arthrothamnus, Cymathaere, Ecklonia, Macrocystis, Nereocystis, Pelagophycus,
      Postelsia, Pseudolessonia, Saccharina, and Streptophyllopsis, which rendered both
      the Laminariaceae and Lessoniaceae monogeneric. A published eight-gene alignment,
      the most marker-rich prior to this study, was expanded and analyzed to facilitate
      inclusion of Aureophycus. Although the topology was unchanged at the family level
      between the transcriptome data set relative to eight-gene analyses, the superior
      resolving power of the former was clearly established.

PMID- 27704554
TI  - Prediction of Clearance in Neonates and Infants (<= 3 Months of Age) for Drugs
      That Are Glucuronidated: A Comparative Study Between Allometric Scaling and
      Physiologically Based Pharmacokinetic Modeling.
AB  - The objective of this study was to evaluate the predictive performances of
      allometric models and a physiologically based pharmacokinetic model (PBPK) to
      predict clearance of glucuronidated drugs in neonates (<= 3 months of age). From
      the literature, clearance values for 9 drugs (glucuronidated) for neonates and
      adults were obtained. Three allometric models were used to predict clearances of
      these glucuronidated drugs. A PBPK model was developed using the physicochemical,
      biopharmaceutical, and metabolic properties together with known pediatric
      physiology and enzymatic ontogeny. The model was first developed for adult
      subjects and then verified using external data and then applied to simulations in
      neonates. The predictive performances of allometric and PBPK models were
      evaluated by comparing the predicted values of clearance with the observed
      clearance values in the neonates. For 9 drugs, there were 13 age groups (preterm
      and term neonates) for which prediction error in mean clearance values within 0.5
      to 1.5-fold was observed in 10 and 11 age groups by 2 allometric models and a
      PBPK model, respectively. The proposed allometric methods can predict mean
      clearances of glucuronidated drugs in preterm and term neonates (<= 3 months of
      age) with reasonable accuracy (within 0.5- to 1.5-fold or 50% error) and are of
      practical value during neonatal drug development. The predicted mean clearance
      values of glucuronidated drugs in neonates <= 3 months of age by 2 allometric
      methods were comparable with the PBPK model.

PMID- 27704556
TI  - Chemistry to conservation: using otoliths to advance recreational and commercial
      fisheries management.
AB  - Otolith chemistry is an effective technique for evaluating fish environmental
      history, but its utility in fisheries management has not been comprehensively
      examined. Thus, a review of otolith chemistry with emphasis on management
      applicability is presented. More than 1500 otolith chemistry manuscripts
      published from 1967 to 2015 are reviewed and descriptive case studies are used to
      illustrate the utility of otolith chemistry as a fisheries management tool.
      Otolith chemistry publications span a wide variety of topics (e.g. natal origins,
      habitat use, movement, stock discrimination and statistical theory) and species
      in freshwater and marine systems. Despite the broad distribution of manuscripts
      in a variety of fisheries, environmental and ecological journals, the majority of
      publications (83%, n = 1264) do not describe implications or applications of
      otolith chemistry for fisheries management. This information gap is addressed
      through case studies that illustrate management applications of otolith
      chemistry. Case studies cover numerous topics (e.g. natal origins, population
      connectivity, stock enhancement, transgenerational marking, pollution exposure
      history and invasive species management) in freshwater and marine systems using
      sport fishes, invasive fishes, endangered fishes and species of commercial and
      aquaculture importance. Otolith chemistry has diverse implications and
      applications for fisheries management worldwide. Collaboration among fisheries
      professionals from academia, government agencies and non-governmental
      organizations will help bridge the research-management divide and establish
      otolith chemistry as a fisheries management tool.

PMID- 27704557
TI  - Storage characteristics of multiple-donor pooled red blood cells compared to
      single-donor red blood cell units.
AB  - BACKGROUND: Each unit of blood donated is processed and stored individually
      resulting in variability in the amount of red blood cells (RBCs) collected, RBC
      properties, and the 24-hour posttransfusion RBC survivability. As a result, each
      unit differs in its ability to deliver oxygen and potentially its effects on the
      recipient. The goal of this study was to investigate the storage of pooled RBCs
      from multiple donors in comparison to control standard RBC units. STUDY DESIGN
      AND METHODS: Two units of irradiated, leukoreduced RBCs of same ABO, D, E, C, and
      K antigen phenotype were collected from each of five donors using apheresis. One
      unit from each donor was pooled in a 2-L bag and remaining units were used as
      controls. After being pooled, RBCs were separated in five bags and stored at 4
      degrees C along with the controls. Quality indexes were measured on Days 2, 14,
      and 28 for all the units. RESULTS: Adenosine triphosphate assays for both pooled
      and controls showed a slight decrease from Day 2 to Day 28 (pooled/control from
      5.22/5.24 to 4.35/4.33 umol/g hemoglobin [Hb]). 2,3-Diphosphoglycerate was
      successfully rejuvenated for all RBC units on Day 28 (pooled 11.46 umol/g Hb;
      control 11.86 umol/g Hb). The results showed a nonsignificant difference between
      pooled and control units, with a general trend of lower standard deviation for
      pooled units when compared to controls. CONCLUSION: Pooled units have reduced
      unit-to-unit variability. Future exploration of their immunogenicity is required
      before using pooled units for transfusion.

PMID- 27704555
TI  - The effects of cold water immersion and active recovery on inflammation and cell
      stress responses in human skeletal muscle after resistance exercise.
AB  - KEY POINTS: Cold water immersion and active recovery are common post-exercise
      recovery treatments. A key assumption about the benefits of cold water immersion
      is that it reduces inflammation in skeletal muscle. However, no data are
      available from humans to support this notion. We compared the effects of cold
      water immersion and active recovery on inflammatory and cellular stress responses
      in skeletal muscle from exercise-trained men 2, 24 and 48 h during recovery after
      acute resistance exercise. Exercise led to the infiltration of inflammatory
      cells, with increased mRNA expression of pro-inflammatory cytokines and
      neurotrophins, and the subcellular translocation of heat shock proteins in
      muscle. These responses did not differ significantly between cold water immersion
      and active recovery. Our results suggest that cold water immersion is no more
      effective than active recovery for minimizing the inflammatory and stress
      responses in muscle after resistance exercise. ABSTRACT: Cold water immersion and
      active recovery are common post-exercise recovery treatments. However, little is
      known about whether these treatments influence inflammation and cellular stress
      in human skeletal muscle after exercise. We compared the effects of cold water
      immersion versus active recovery on inflammatory cells, pro-inflammatory
      cytokines, neurotrophins and heat shock proteins (HSPs) in skeletal muscle after
      intense resistance exercise. Nine active men performed unilateral lower-body
      resistance exercise on separate days, at least 1 week apart. On one day, they
      immersed their lower body in cold water (10 degrees C) for 10 min after exercise.
      On the other day, they cycled at a low intensity for 10 min after exercise.
      Muscle biopsies were collected from the exercised leg before, 2, 24 and 48 h
      after exercise in both trials. Exercise increased intramuscular neutrophil and
      macrophage counts, MAC1 and CD163 mRNA expression (P < 0.05). Exercise also
      increased IL1beta, TNF, IL6, CCL2, CCL4, CXCL2, IL8 and LIF mRNA expression (P <
      0.05). As evidence of hyperalgesia, the expression of NGF and GDNF mRNA increased
      after exercise (P < 0.05). The cytosolic protein content of alphaB-crystallin and
      HSP70 decreased after exercise (P < 0.05). This response was accompanied by
      increases in the cytoskeletal protein content of alphaB-crystallin and the
      percentage of type II fibres stained for alphaB-crystallin. Changes in
      inflammatory cells, cytokines, neurotrophins and HSPs did not differ
      significantly between the recovery treatments. These findings indicate that cold
      water immersion is no more effective than active recovery for reducing
      inflammation or cellular stress in muscle after a bout of resistance exercise.

PMID- 27704558
TI  - Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in
      BSP-/- Mice, Along With Faster Hematopoietic Recolonization.
AB  - The bone organ integrates the activity of bone tissue, bone marrow, and blood
      vessels and the factors ensuring this coordination remain ill defined. Bone
      sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin
      binding ligand N-linked glycoprotein (SIBLING) family, involved in bone
      formation, hematopoiesis and angiogenesis. In rodents, bone marrow ablation
      induces a rapid formation of medullary bone which peaks by ~8 days (d8) and is
      blunted in BSP-/- mice. We investigated the coordinate hematopoietic and vascular
      recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and
      BSP-/- mice. At d3, the ablated area in BSP-/- femurs showed higher vessel
      density (*4) and vascular volume (*7) than BSP+/+. Vessel numbers in the shaft of
      ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume
      which was twice the value in BSP-/-, reflecting smaller vessel size in ablated
      mutants. At d6, a much higher number of Lin- (*3) as well as LSK (Lin- IL-7Ralpha
      Sca-1hi c-Kithi , *2) and hematopoietic stem cells (HSC: Flt3- LSK, *2) were
      counted in BSP-/- marrow, indicating a faster recolonization. However, the
      proportion of LSK and HSC within the Lin- was lower in BSP-/- and more
      differentiated stages were more abundant, as also observed in unablated bone,
      suggesting that hematopoietic differentiation is favored in the absence of BSP.
      Interestingly, unablated BSP-/- femur marrow also contains more blood vessels
      than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are
      higher, and DMP1 lower in the mutants. In conclusion, bone marrow ablation in BSP
      /- mice is followed by a faster vascular and hematopoietic recolonization, along
      with lower medullary bone formation. Thus, lack of BSP affects the interplay
      between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through
      higher expression of VEGF and the angiogenic SIBLING, OPN. J. Cell. Physiol. 232:
      2528-2537, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27704559
TI  - A randomized crossover study comparing membrane and centrifugal therapeutic
      plasma exchange procedures.
AB  - BACKGROUND: Therapeutic plasma exchange (TPE) can be performed either on a
      membrane-based system (mTPE) or on a device that separates blood components by
      centrifugation (cTPE). The number of studies in this field is limited. This
      randomized study is the first that offers data on the membrane-based Diapact
      device (B. Braun Medical, Inc.) for TPE procedures and compares it to the
      centrifuge-based Spectra Optia (Terumo BCT, Inc.). STUDY DESIGN AND METHODS:
      Twenty-seven patients were enrolled in this randomized prospective head-to-head
      study comparing the mTPE and cTPE systems. Procedures on both devices were
      standardized and the plasma removal efficiency (PRE); total procedure time
      (including setup and priming time); and removal efficiencies of blood cells,
      immunoglobulin (Ig)G, and fibrinogen for all procedures were analyzed. RESULTS:
      While both systems removed similar amounts of plasma, it took the cTPE device a
      mean of 101.5 +/- 24.6 minutes to finalize a procedure that was one-third less
      than procedures on the mTPE device (157 +/- 26.2 min; p < 0.0001), due to a
      difference in PRE between the Spectra Optia (83.0% +/- 4.9%) and the Diapact
      (53.2% +/- 6.6%; p < 0.0001). The difference in removal efficiencies of IgG and
      blood cells were not significantly different but the Spectra Optia was more
      efficient in removing the larger fibrinogen protein than the Diapact (72.3% +/-
      8.5% vs. 62.9% +/- 16.1%, respectively; p < 0.02). CONCLUSION: This study shows
      that, although both systems perform adequate and safe TPE procedures, those on
      the Spectra Optia in comparison to the Diapact are more efficient in terms of
      plasma removal and significantly shorter.

PMID- 27704560
TI  - Using complementary approaches to identify trans-domain nuclear gene transfers in
      the extremophile Galdieria sulphuraria (Rhodophyta).
AB  - Identification of horizontal gene transfers (HGTs) has primarily relied on
      phylogenetic tree based methods, which require a rich sampling of sequenced
      genomes to ensure a reliable inference. Because the success of phylogenetic
      approaches depends on the breadth and depth of the database, researchers usually
      apply stringent filters to detect only the most likely gene transfers in the
      genomes of interest. One such study focused on a highly conservative estimate of
      trans-domain gene transfers in the extremophile eukaryote, Galdieria sulphuraria
      (Galdieri) Merola (Rhodophyta), by applying multiple filters in their
      phylogenetic pipeline. This led to the identification of 75 inter-domain
      acquisitions from Bacteria or Archaea. Because of the evolutionary, ecological,
      and potential biotechnological significance of foreign genes in algae,
      alternative approaches and pipelines complementing phylogenetics are needed for a
      more comprehensive assessment of HGT. We present here a novel pipeline that
      uncovered 17 novel foreign genes of prokaryotic origin in G. sulphuraria, results
      that are supported by multiple lines of evidence including composition-based,
      comparative data, and phylogenetics. These genes encode a variety of potentially
      adaptive functions, from metabolite transport to DNA repair.

PMID- 27704561
TI  - Why Does Disaster Recovery Work Influence Mental Health?: Pathways through
      Physical Health and Household Income.
AB  - Disaster recovery work increases risk for mental health problems, yet the
      mechanisms underlying this association are unclear. We explored links from
      recovery work to post-traumatic stress (PTS), major depression (MD), and
      generalized anxiety disorder (GAD) symptoms through physical health symptoms and
      household income in the aftermath of the Deepwater Horizon oil spill. As part of
      the NIEHS GuLF STUDY, participants (N = 10,141) reported on cleanup work
      activities, spill-related physical health symptoms, and household income at
      baseline, and mental health symptoms an average of 14.69 weeks (SD = 16.79)
      thereafter. Cleanup work participation was associated with higher physical health
      symptoms, which in turn were associated with higher PTS, MD, and GAD symptoms.
      Similar pattern of results were found in models including workers only and
      investigating the influence of longer work duration and higher work-related oil
      exposure on mental health symptoms. In addition, longer worker duration and
      higher work-related oil exposure were associated with higher household income,
      which in turn was associated with lower MD and GAD symptoms. These findings
      suggest that physical health symptoms contribute to workers' risk for mental
      health symptoms, while higher household income, potentially from more extensive
      work, might mitigate risk.

PMID- 27704562
TI  - Efavirenz does not meaningfully affect the single dose pharmacokinetics of 1200
      mg raltegravir.
AB  - Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer
      inhibitor currently marketed at a dose of 400 mg twice daily (BID). Raltegravir
      for once daily regimen (QD) at a dose of 1200 mg (2 x 600 mg) is under
      development and offers a new treatment option for HIV-1 infected treatment-naive
      subjects. Since raltegravir is eliminated mainly by metabolism via an UDP
      glucuronosyltransferase (UGT) 1 A1-mediated glucuronidation pathway, co
      administration of UGT1A1 inducers may alter plasma levels of raltegravir.
      Efavirenz, an UGT1A1 inducer, was used to assess the impact of altered UGT
      activity on a 1200 mg QD dose of raltegravir. An open label, randomized, 2-period
      fixed-sequence Phase 1 study was performed in adult healthy male and female
      subjects (non-childbearing potential) >= 19 and <=55 years of age, with a body
      mass index (BMI) >= 18.5 and <=32.0 kg/m2 . Subjects (n = 21) received a single
      oral dose of 1200 mg raltegravir at bedtime on an empty stomach on Day 1 in
      Period 1. After a washout period of at least 7 days, subjects received oral doses
      of 600 mg efavirenz QD at bedtime for 14 consecutive days in Period 2. Subjects
      received a single oral dose of 1200 mg raltegravir co-administered with 600 mg
      efavirenz on Day 12 of Period 2. Pharmacokinetic (PK) samples were collected for
      72 hours following raltegravir dosing and analyzed using a validated
      bioanalytical method to quantify raltegravir plasma concentrations. PK parameters
      were estimated using non-compartmental analysis. Administration of single 1200 mg
      oral doses of raltegravir alone and co-administered with multiple oral doses of
      efavirenz were generally well tolerated in healthy subjects. Co-administration
      with efavirenz yielded geometric mean ratios (GMRs) and their associated 90%
      confidence intervals (90% CIs) for raltegravir AUC0-infinity, Cmax , and C24 of
      0.86 (0.73, 1.01), 0.91 (0.70, 1.17), and 0.94 (0.76, 1.17), respectively. The
      results show that efavirenz modestly reduced the exposure of raltegravir. The
      reduction in raltegravir exposure is not considered clinically meaningful.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27704564
TI  - Indispensable Role of Ion Channels and Transporters in the Auditory System.
AB  - Ear is a complex system where appropriate ionic composition is essential for
      maintaining the tissue homeostasis and hearing function. Ion transporters and
      channels present in the auditory system plays a crucial role in maintaining
      proper ionic composition in the ear. The extracellular fluid, called endolymph,
      found in the cochlea of the mammalian inner ear is particularly unique due to its
      electrochemical properties. At an endocochlear potential of about +80 mV,
      signaling initiated by acoustic stimuli at the level of the hair cells is
      dependent on the unusually high potassium (K+ ) concentration of endolymph. There
      are ion channels and transporters that exists in the ear to ensure that K+ is
      continually being cycled into the stria media endolymph. This review is focused
      on the discussion of the molecular and genetic basis of previously and newly
      recognized ion channels and transporters that support sensory hair cell
      excitation based on recent knock-in and knock-out studies of these channels. This
      article also addresses the molecular and genetic defects and the pathophysiology
      behind Meniere's disease as well as how the dysregulation of these ion
      transporters can result in severe defects in hearing or even deafness.
      Understanding the role of ion channels and transporters in the auditory system
      will facilitate in designing effective treatment modalities against ear disorders
      including Meniere's disease and hearing loss. J. Cell. Physiol. 232: 743-758,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27704563
TI  - Induction of peptidylarginine deiminase 2 and 3 by dibutyryl cAMP via cAMP-PKA
      signaling in human astrocytoma U-251MG cells.
AB  - Peptidylarginine deiminases (PADs) are posttranslational modification enzymes
      that citrullinate (deiminate) protein arginine residues in a calcium-dependent
      manner, yielding citrulline residues. Enzymatic citrullination abolishes positive
      charges of native protein molecules, inevitably causing significant alterations
      in their structure and function. Previously, we reported the abnormal
      accumulation of citrullinated proteins and an increase of PAD2 content in
      hippocampi of patients with Alzheimer disease. In this study, we investigated PAD
      expression by using dibutyryl cAMP (dbcAMP) in human astrocytoma U-251MG cells.
      Under normal culture conditions, PAD2 and PAD3 mRNA expression is detectable with
      quantitative PCR in U-251MG cells. The addition of dbcAMP in a dose-dependent
      manner significantly increased this mRNA expression and protein levels. Moreover,
      PAD enzyme activity also increased significantly and dose-dependently.
      Furthermore, the expression of PAD2 and PAD3 mRNA was inhibited by the cAMP
      dependent PKA inhibitor KT5720, suggesting that such expression of dbcAMP-induced
      PAD2 and PAD3 mRNA is mediated by the cAMP-PKA signaling pathway in U-251MG
      cells. This is the first report to document the PAD2 and PAD3 mRNA expression
      induced by dbcAMP and to attribute the induction of these genes to mediation by
      the cAMP-PKA signaling pathway in U-251MG cells. (c) 2016 Wiley Periodicals, Inc.

PMID- 27704565
TI  - Communities of practice: A means to support occupational therapists' continuing
      professional development. A literature review.
AB  - BACKGROUND: This literature review investigates what research reports about the
      contribution that communities of practice (CoPs) can make in the continuing
      professional development (CPD) of qualified occupational therapists. METHODS:
      Academic databases (CINAHL, MEDLINE and ERIC) were searched and articles were
      included based on pre-determined criteria. Five articles were included in the
      review. RESULTS: The CoPs in the reviewed articles provided opportunities for
      knowledge sharing, knowledge translation, reflection on action and learning
      through boundary crossing. The presence of professionals with diverse
      perspectives was an important ingredient that facilitated CPD. CONCLUSION:
      Research into the use of CoPs in occupational therapy is sparse. CoPs could
      provide a CPD forum for occupational therapists whether online or face to face.
      Practitioners are encouraged to participate in CoPs. Further research into the
      use of CoPs is recommended.

PMID- 27704566
TI  - W. R. D. FAIRBAIRN AND THE PROBLEM OF HOMOSEXUALITY: A STUDY IN PSYCHOANALYTIC
      PREJUDICE.
AB  - W. R. D. Fairbairn believed that the psychoanalyst's motivations and theories
      must ultimately be rooted in a need to resolve personal conflicts. His self
      analytic and other records, now publicly available, indicate how his struggles
      with unacceptable sexual feelings and their symptomatic manifestations affected
      not only his theorizing, especially about sexuality, but also his clinical
      practice, as well as his personal and family life. Fairbairn's case affords a
      unique opportunity to document the effects of homophobia in a major
      psychoanalyst.

PMID- 27704567
TI  - PSYCHOANALYSIS IN CHINA: AN ESSAY ON THE RECENT LITERATURE IN ENGLISH.
AB  - Using extensive quotation, the author reviews the introduction and current state
      of psychoanalysis and psychoanalytic psychotherapy in China from the vantage
      point of recent publications in English. Psychoanalysis was briefly introduced to
      China before the Communist era, then forbidden, and has experienced an
      accelerated reintroduction since the late 1980s. The author briefly summarizes
      the cultural and historical background of China relevant to the introduction of
      psychoanalysis, the traumatic history of China, and the deep structure of thought
      and philosophical differences from Western culture that challenge a simple
      imposition of psychoanalytic ideas and practice, and some psychological effects
      of rapid cultural change throughout China. Training programs in China, the
      general enthusiasm for analysis among the Chinese, and a number of notable
      contributions by Western and Chinese authors are discussed. Also surveyed are the
      use of distance technology for training and treatment, the personal experience of
      Chinese senior and junior colleagues, and ongoing challenges to the continuing
      growth of psychoanalysis and analytic psychotherapy in China.

PMID- 27704568
TI  - THE LAST ASYLUM: A MEMOIR OF MADNESS IN OUR TIMES. By Barbara Taylor.

PMID- 27704569
TI  - THE DESIRE FOR THERAPEUTIC GAIN: COMMENTARY ON CHUSED'S "AN ANALYST'S UNCERTAINTY
      AND FEAR".

PMID- 27704570
TI  - KARL ABRAHAM: THE BIRTH OF OBJECT RELATIONS THEORY. By Isabel Sanfeliu;
      translated by Kate Walters.

PMID- 27704571
TI  - THE GIRL WHO COMMITTED HARA-KIRI AND OTHER CLINICAL AND HISTORICAL ESSAYS. By
      Franco Borgogno; translated by Alice Spence.

PMID- 27704572
TI  - FREUD AND THE SPOKEN WORD: SPEECH AS A KEY TO THE UNCONSCIOUS. By Ana-Maria
      Rizzuto.

PMID- 27704573
TI  - COMMENTS ON JUDITH FINGERT CHUSED'S "AN ANALYST'S UNCERTAINTY AND FEAR".

PMID- 27704574
TI  - CONTEMPORARY PSYCHOANALYSIS AND THE LEGACY OF THE THIRD REICH: HISTORY, MEMORY,
      AND TRADITION. By Emily A.

PMID- 27704575
TI  - A TRICK IN A DREAM: ON THE DREAM WORK'S IMPRESSIVE CREATIVITY.

PMID- 27704576
TI  - AN ANALYST'S UNCERTAINTY AND FEAR.
AB  - The motivations for choosing psychoanalysis as a profession are many and differ
      depending on the psychology of the analyst. However, common to most
      psychoanalysts is the desire to forge a helpful relationship with the individuals
      with whom they work therapeutically. This article presents an example of what
      happens when an analyst is confronted by a patient for whom being in a
      relationship and being helped are intolerable.

PMID- 27704577
TI  - SELF PSYCHOLOGY AND PSYCHOSIS: THE DEVELOPMENT OF THE SELF DURING INTENSIVE
      PSYCHOTHERAPY OF SCHIZOPHRENIA AND OTHER PSYCHOSES. By David Garfield and Ira
      Steinman.

PMID- 27704578
TI  - RESPONSE TO COMMENTARIES ON MY PAPER, "AN ANALYST'S UNCERTAINTY AND FEAR".

PMID- 27704579
TI  - THE DIALOGICAL SELF IN PSYCHOANALYSIS.
AB  - This paper describes the shift that appears to be taking place in contemporary
      psychoanalysis, as reflected among intersubjective approaches, from a monological
      conception of the self to a dialogical one. The monological self emphasizes the
      separation between mind, body, and external world, focusing on the
      representational and descriptive/referential function of language. In contrast,
      the dialogical self emphasizes practices, the permeable nature of relationships
      between subjects, and the constitutive function of language. This paper attempts
      to explain the growing emphasis on the dialogical self, understood from a
      theoretical, metatheoretical, and technical point of view, using contemporary
      intersubjective approaches to illustrate this shift.

PMID- 27704580
TI  - EDITOR'S INTRODUCTION.

PMID- 27704581
TI  - WHEN THE SUN BURSTS: THE ENIGMA OF SCHIZOPHRENIA. By Christopher Bollas.

PMID- 27704582
TI  - COMMENTARY ON JUDITH FINGERT CHUSED'S "AN ANALYST'S UNCERTAINTY AND FEAR".

PMID- 27704583
TI  - THE PROMISE: WHO IS IN CHARGE OF TIME AND SPACE? By Leonard Shengold.

PMID- 27704584
TI  - A comparative study of the hypolipidaemic effects of a new polysaccharide, mannan
      Candida albicans serotype A, and atorvastatin in mice with poloxamer 407-induced
      hyperlipidaemia.
AB  - OBJECTIVES: We evaluated the hypolipidaemic effect of mannan Candida albicans
      serotype A, relative to atorvastatin, in a mouse model of hyperlipidaemia.
      METHODS: Mannan serotype A was investigated in vitro and in vivo to determine its
      effects on macrophage proliferation, nitric oxide (NO) production by cultured
      macrophages, serum and liver lipids, changes in liver morphology and serum
      chitotriosidase activity and its expression in the liver. KEY FINDINGS: Mannan
      serotype A stimulates the macrophage proliferation and NO production in murine
      peritoneal macrophages in vitro. The activity of serum chitotriosidase (an enzyme
      released from the activated macrophages) was found to be significantly increased
      in P-407-induced hyperlipidaemic mice pretreated with low-dose mannan compared
      with mice administered P-407 only. Mannan treatment in mice was shown to
      significantly increase the chitotriosidase expression in the liver of both non
      hyperlipidaemic and P-407-induced hyperlipidaemic mice. Lastly, mice pretreated
      with mannan before the induction of hyperlipidaemia with P-407 showed a
      significant reduction in the serum concentration of atherogenic LDL cholesterol,
      total cholesterol, triglycerides and liver triglycerides. CONCLUSIONS: It is
      suggested that mannan serotype A, like beta-glucan, may represent another
      hypolipidaemic agent, which could potentially be used as an adjunctive therapy
      with conventional antihyperlipidaemic drugs (statins and fibrates) in humans.

PMID- 27704585
TI  - Complete genome sequence of a KI polyomavirus isolated from an otherwise healthy
      child with severe lower respiratory tract infection.
AB  - Unbiased, deep sequencing of a nasal specimen from an otherwise healthy 13-month
      old boy hospitalized in intensive care revealed high gene expression and the
      complete genome of a novel isolate of KI polyomavirus (KIPyV). Further
      investigation detected minimal gene expression of additional viruses, suggesting
      that KIPyV was potentially the causal agent. Analysis of the complete genome of
      isolate NMKI001 revealed it is different from all previously reported genomes and
      contains two amino acid differences as compared to the closest virus isolate,
      Stockholm 380 (EF127908). J. Med. Virol. 89:926-930, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27704586
TI  - Hypermethylation of PRDM1/Blimp-1 promoter in extranodal NK/T-cell lymphoma,
      nasal type: an evidence of predominant role in its downregulation.
AB  - The loss of PRDM1 expression is common in extranodal NK/T-cell lymphoma, nasal
      type (EN-NK/T-NT), but the role of promoter methylation in silencing PRDM1
      expression remains unclear. Hence, we performed pyrosequencing analysis to
      evaluate the promoter methylation of PRDM1 gene in vivo and in vitro, to analyze
      the association between methylation and its expression, and to assess cellular
      effects of PRDM1 reexpression. The promoter hypermethylation of PRDM1 gene was
      detected in 11 of 25 EN-NK/T-NT cases (44.0%) and NK92 and NKL cells. The
      promoter hypermethylation of PRDM1 was significantly correlated with PRDM1
      expression in vivo and in vitro, predominantly contributing to the loss of PRDM1
      expression compared with genetic deletion and aberrant expression of miR-223 in
      EN-NK/T-NT. PRDM1 expression was significantly restored by demethylation
      treatment, which induced cell proliferation suppression, cell cycle arrest, and
      apoptosis increase. We also found that PRDM1 reexpression could downregulate the
      expression of Ets-1, T-bet, granzyme B, and c-myc. Our findings demonstrated that
      the promoter hypermethylation of PRDM1 harbored a predominant role in the
      downregulation of PRDM1 expression, significantly affecting the biological
      behavior of tumor cells in EN-NK/T-NT.

PMID- 27704587
TI  - Postdeployment Suicide Risk Increases Over a 6-month Period: Predictors of
      Increased Risk among Midwestern Army National Guard Soldiers.
AB  - National Guard (NG) soldiers returning from deployments in Iraq and Afghanistan
      were surveyed at 6 and 12 months following their return (N = 970). The overall
      prevalence of suicide risk at 6 and 12 months following their return was
      assessed, as were changes in suicide risk among soldiers initially at high or low
      risk. Factors associated with changes in risk were assessed. The percentage of NG
      soldiers with high suicide risk increased from 6.8% at 6 months to 9.2% at 12
      months (odds ratio = 1.7, p = .02). In the 882 soldiers initially at low risk,
      5.9% (52/882) became high risk at 12 months; in the 64 soldiers initially at high
      risk, 46.9% (30/64) became low risk at 12 months. Initial levels of depressive
      symptoms were predictive of changing to high risk; this association appeared to
      be partially explained by soldier reports of increased search in the meaning in
      life and higher levels of perceived stress. Because suicide risk increases over
      the first 12 months, continued risk assessments during this time period should be
      considered. Supporting soldiers to find meaning in their life after deployment
      and enhancing their capacity to cope with perceived stress may help prevent
      increases in suicide risk over time.

PMID- 27704588
TI  - Assessment of Web-based education resources informing patients about stroke
      prevention in atrial fibrillation.
AB  - WHAT IS KNOWN AND OBJECTIVE: The importance of 'shared decision-making' is much
      emphasized in recent clinical guidelines regarding stroke management in atrial
      fibrillation (AF), more so following the inclusion of non-vitamin K oral
      anticoagulants (NOACs) among the treatment options. It is important that patients
      are navigated through balanced and unbiased information about the available
      treatment options, so as to understand the risk and benefits associated with the
      therapies, and to enable them to accordingly communicate their concerns and views
      with their clinicians prior to therapy selection. Given the increasing popularity
      of the Internet as a source of health information, the specific objectives of
      this study were to identify what aspects of thromboprophylaxis (antithrombotic
      treatment options) were most commonly described in these resources, both in terms
      of content, that is to report the information provided (quantitative) and the
      underlying themes underpinning this content, and in terms of how this information
      might guide patient preferences (qualitative). METHOD: Resources for patients
      were identified via online search engines (Google, Yahoo, Ask, Bing), using the
      terms 'atrial fibrillation' and 'stroke' combined with patient/consumer
      information, patient/consumer resources and patient/consumer education. The
      researchers employed pragmatic (mix-method) approach to analyse the information
      presented within the resources using manual inductive coding, at two levels of
      analysis: manifest (reported surface theme or codes that are obvious and are
      countable) and latent (thematic, interpretative presentation of the content in
      the data set). RESULTS AND DISCUSSION: In total, 33 resources were reviewed. The
      'manifest-level' analysis found that warfarin was the most frequently mentioned
      thromboprophylactic option among the anticoagulants, being cited in all
      resources, followed by the NOACs - dabigatran (82.3% of resources), rivaroxaban
      (73.5%) and apixaban (67.6%). Only one-third of resources discussed the role of
      stroke risk and/or bleeding risk within the decision-making. At the 'latent
      level' analysis, three overarching themes emerged: (i) The practical ease of
      managing NOACs over warfarin; (ii) Unbalanced explanation about stroke risk
      versus bleeding risk; and (iii) Individualized antithrombotic therapy selection.
      In general, the benefit of stroke prevention with anticoagulant use was
      emphasized less compared to the risk of bleeding. Overall, one in four resources
      had an implied preference for either warfarin or the NOACs. WHAT IS NEW AND
      CONCLUSION: The implied inclination of some resources towards particular
      anticoagulant therapies and imbalanced information about the importance of
      anticoagulation in AF might misinform and confuse patients. Patients' engagement
      in shared decision-making and adherence to medicines may be undermined by the
      suboptimal quality of information provided in the resources. Health professionals
      have an important role to play in referring patients to appropriate resources to
      enable patient engagement in shared decision-making when selecting treatment.

PMID- 27704589
TI  - Identifying research priorities with nurses at a tertiary children's hospital in
      the United Kingdom.
AB  - AIM: The objective of this study was to undertake a research priority setting
      exercise with the aim of maximizing efficiency and impact in research activity
      undertaken by nurses at one children's tertiary healthcare institution by
      ensuring the clinical staff directly shaped a coherent, transparent and consensus
      driven nurse-led research agenda. BACKGROUND: In Round 1, the research topics of
      147 nurses were elicited using a modified nominal group technique as the
      consensus method. The number of participants in the 24 separate discussions
      ranged from 3 to 21, generating lists of between 6 and 23 topics. In Round 2,
      nurses from the clinical areas ranked topics of importance resulting in a set of
      four to five priorities. In Round 3, the divisional heads of nursing consulted
      with staff in all of their clinical areas to each finalize their five divisional
      priorities. The Nursing Research Working Group discussed and refined the
      divisions' priorities and voted on the final list to agree the top five research
      priorities for the organization. RESULTS: A total of 269 research topics were
      initially generated. Following three rounds of ranking and prioritizing, five
      priorities were agreed at Divisional level, and from these, the five top
      organizational priorities were selected. These were (i) understanding and
      improving all aspects of the patient journey through the hospital system; (ii)
      play; (iii) staff wellbeing, patient care and productivity; (iv) team work -
      linking to a more efficient service; and (v) supporting parents/parent pathway.
      CONCLUSIONS: Divisional priorities have been disseminated widely to clinical
      teams to inform a patient-specific nurse-led research agenda. Organizational
      priorities agreed upon have been disseminated through management structures and
      processes to ensure engagement at all levels. A subgroup of the Nursing Research
      Working Group has been delegated to take this work forward so that the agreed
      priorities continue to contribute towards shaping nurse-led research activity,
      thereby going some way to inform and embed an evidence-based culture of inquiry.

PMID- 27704590
TI  - Evaluating the Incredible Years Toddler Parenting Programme with parents of
      toddlers in disadvantaged (Flying Start) areas of Wales.
AB  - BACKGROUND: Early risk factors for poor child outcomes are well established, and
      some group parenting programmes have demonstrated good outcomes for children
      under 3 years of age. This randomized controlled trial evaluated the
      effectiveness of the Incredible Years(r) Toddler Parenting Programme with parents
      of 1-year-old and 2-year-old children recruited by staff in disadvantaged Flying
      Start areas across Wales. METHODS: Eighty-nine families with a child aged between
      12 and 36 months at baseline participated in a pragmatic community-based trial of
      the programme in eight Flying Start areas. Outcomes were measured at baseline, 6
      months and 12 months using measures of parental mental health, competence, child
      behaviour, child development, home environment and blinded-observation of parent
      child interactions. RESULTS: Significant intervention group improvements were
      found in parental mental well-being and observed praise at 6 months. Significant
      improvements for the intervention group at 12 months included child development,
      home environment and parental depression. CONCLUSION: The study provides
      preliminary evidence for programme attendance.

PMID- 27704591
TI  - A cell-based high-throughput protocol to screen entry inhibitors of highly
      pathogenic viruses with Traditional Chinese Medicines.
AB  - Emerging viruses such as Ebola virus (EBOV), Lassa virus (LASV), and avian
      influenza virus H5N1 (AIV) are global health concerns. Since there is very
      limited options (either vaccine or specific therapy) approved for humans against
      these viruses, there is an urgent need to develop prophylactic and therapeutic
      treatments. Previously we reported a high-throughput screening (HTS) protocol to
      identify entry inhibitors for three highly pathogenic viruses (EBOV, LASV, and
      AIV) using a human immunodeficiency virus-based pseudotyping platform which
      allows us to perform the screening in a BSL-2 facility. In this report, we have
      adopted this screening protocol to evaluate traditional Chinese Medicines (TCMs)
      in an effort to discover entry inhibitors against these viruses. Here we show
      that extracts of the following Chinese medicinal herbs exhibit potent anti-Ebola
      viral activities: Gardenia jasminoides Ellis, Citrus aurantium L., Viola
      yedoensis Makino, Prunella vulgaris L., Coix lacryma-jobi L. var. mayuen (Roman.)
      Stapf, Pinellia ternata (Thunb.) Breit., and Morus alba L. This study represents
      a proof-of-principle investigation supporting the suitability of this assay for
      rapid screening TCMs and identifying putative entry inhibitors for these viruses.
      J. Med. Virol. 89:908-916, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27704592
TI  - Guidelines for Use of the Approximate Beta-Poisson Dose-Response Model.
AB  - For dose-response analysis in quantitative microbial risk assessment (QMRA), the
      exact beta-Poisson model is a two-parameter mechanistic dose-response model with
      parameters alpha>0 and beta>0, which involves the Kummer confluent hypergeometric
      function. Evaluation of a hypergeometric function is a computational challenge.
      Denoting PI(d) as the probability of infection at a given mean dose d, the widely
      used dose-response model PI(d)=1-(1+dbeta)-alpha is an approximate formula for
      the exact beta-Poisson model. Notwithstanding the required conditions alpha<<beta
      and beta>>1, issues related to the validity and approximation accuracy of this
      approximate formula have remained largely ignored in practice, partly because
      these conditions are too general to provide clear guidance. Consequently, this
      study proposes a probability measure Pr(0 < r < 1 | alpha, beta) as a validity
      measure (r is a random variable that follows a gamma distribution; alpha and beta
      are the maximum likelihood estimates of alpha and beta in the approximate model);
      and the constraint conditions beta>(22alpha)0.50 for 0.02<alpha<2 as a rule of
      thumb to ensure an accurate approximation (e.g., Pr(0 < r < 1 | alpha, beta)
      >0.99) . This validity measure and rule of thumb were validated by application to
      all the completed beta-Poisson models (related to 85 data sets) from the QMRA
      community portal (QMRA Wiki). The results showed that the higher the probability
      Pr(0 < r < 1 | alpha, beta), the better the approximation. The results further
      showed that, among the total 85 models examined, 68 models were identified as
      valid approximate model applications, which all had a near perfect match to the
      corresponding exact beta-Poisson model dose-response curve.

PMID- 27704593
TI  - Design of clinical trials involving multiple hypothesis tests with a common
      control.
AB  - Randomized clinical trials comparing several treatments to a common control are
      often reported in the medical literature. For example, multiple experimental
      treatments may be compared with placebo, or in combination therapy trials, a
      combination therapy may be compared with each of its constituent monotherapies.
      Such trials are typically designed using a balanced approach in which equal
      numbers of individuals are randomized to each arm, however, this can result in an
      inefficient use of resources. We provide a unified framework and new theoretical
      results for optimal design of such single-control multiple-comparator studies. We
      consider variance optimal designs based on D-, A-, and E-optimality criteria,
      using a general model that allows for heteroscedasticity and a range of effect
      measures that include both continuous and binary outcomes. We demonstrate the
      sensitivity of these designs to the type of optimality criterion by showing that
      the optimal allocation ratios are systematically ordered according to the
      optimality criterion. Given this sensitivity to the optimality criterion, we
      argue that power optimality is a more suitable approach when designing clinical
      trials where testing is the objective. Weighted variance optimal designs are also
      discussed, which, like power optimal designs, allow the treatment difference to
      play a major role in determining allocation ratios. We illustrate our methods
      using two real clinical trial examples taken from the medical literature. Some
      recommendations on the use of optimal designs in single-control multiple
      comparator trials are also provided.

PMID- 27704594
TI  - l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic
      cerebrovascular disease: A systematic review.
AB  - Endothelial dysfunction (ED), in particular cerebral ED, may be an essential
      biomarker for ischaemic cerebrovascular disease. However, there is no consensus
      on methods to best estimate cerebral ED. In this systematic review, we evaluate
      the use of l-arginine and NG -monomethyl-l-arginine (l-NMMA) for assessment of
      cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was
      done. We included studies investigating cerebrovascular response to l-arginine or
      l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular
      disease. Seven studies (315 subjects) were eligible according to inclusion and
      exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes
      mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior
      ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most
      studies applied transcranial Doppler to quantify cerebral ED. Endothelium
      dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and
      subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including
      subjects with prior ischaemic stroke or TIA reported both enhanced and impaired
      EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM
      and the elderly. We found only few studies investigating cerebral endothelial
      responses to l-arginine and l-NMMA in subjects with vascular risk factors or
      ischaemic cerebrovascular disease. Inconsistencies in results were most likely
      due to variations in methods and included subject populations. In order to use
      cerebral ED as a prognostic marker, further studies are required to evaluate the
      association to cerebrovascular disease.

PMID- 27704596
TI  - A vocational rehabilitation intervention for young adults with physical
      disabilities: participants' perception of beneficial attributes.
AB  - BACKGROUND: Finding and maintaining employment is a major challenge for young
      adults with physical disabilities and their work participation rate is lower than
      that of healthy peers. This paper is about a program that supports work
      participation amongst young adults with chronic physical disabilities. The study
      aims to explore their experienced barriers and facilitators for finding and
      maintaining employment after starting this program, the participant-perceived
      beneficial attributes of the program and participants' recommendations for
      additional intervention components. METHODS: Semi-structured interviews (n = 19)
      were held with former intervention participations. Interviews were recorded and
      transcribed ad verbatim. Themes were derived using the phenomenological approach.
      RESULTS: Physical functions and capacities, supervisor's attitude, self-esteem
      and self-efficacy and openness and assertiveness were experienced barriers and
      facilitators for finding and maintaining employment. Improvement of self
      promoting skills and disclosure skills through job interview-training, increased
      self-esteem or self-efficacy through peer-support, a suitable job through job
      placement, improvement of work ability through arrangement of adjusted work
      conditions and change of supervisor's attitude through education provided to the
      supervisor were perceived as beneficial attributes of the intervention.
      Respondents recommended to incorporate assertiveness and openness skills training
      into future intervention programs. CONCLUSIONS: The findings suggest that
      programs supporting work participation should be designed to provide challenging,
      real-world experiential opportunities that provide young adults with physical
      disabilities with new insights, self-efficacy and life skills. Also, such
      programs should facilitate context centered learning. Former intervention
      participants, therefore, evaluated job-interview training, sharing learning and
      social experiences with peers, job placement, arrangement of adjusted work
      conditions and education as beneficial attributes of the 'At Work' program. In
      addition, they recommended, to incorporate more training on assertiveness and
      disclosure. We advise professionals to include these beneficial attributes in
      similar interventions in other contexts.

PMID- 27704595
TI  - Cholinergic regulation of fear learning and extinction.
AB  - Cholinergic activation regulates cognitive function, particularly long-term
      memory consolidation. This Review presents an overview of the anatomical,
      neurochemical, and pharmacological evidence supporting the cholinergic regulation
      of Pavlovian contextual and cue-conditioned fear learning and extinction. Basal
      forebrain cholinergic neurons provide inputs to neocortical regions and
      subcortical limbic structures such as the hippocampus and amygdala.
      Pharmacological manipulations of muscarinic and nicotinic receptors support the
      role of cholinergic processes in the amygdala, hippocampus, and prefrontal cortex
      in modulating the learning and extinction of contexts or cues associated with
      threat. Additional evidence from lesion studies and analysis of in vivo
      acetylcholine release with microdialysis similarly support a critical role of
      cholinergic neurotransmission in corticoamygdalar or corticohippocampal circuits
      during acquisition of fear extinction. Although a few studies have suggested a
      complex role of cholinergic neurotransmission in the cellular plasticity
      essential for extinction learning, more work is required to elucidate the exact
      cholinergic mechanisms and physiological role of muscarinic and nicotinic
      receptors in these fear circuits. Such studies are important for elucidating the
      role of cholinergic neurotransmission in disorders such as posttraumatic stress
      disorder that involve deficits in extinction learning as well as for developing
      novel therapeutic approaches for such disorders. (c) 2016 Wiley Periodicals, Inc.

PMID- 27704597
TI  - Willingness of Mentally Ill Individuals to Sign Up for a Novel Proposal to
      Prevent Firearm Suicide.
AB  - The study goal was to determine whether a significant number of high suicide risk
      individuals would confidentially put their own names onto a list to prevent
      future gun purchases. An anonymous written survey was administered in an
      inpatient psychiatric unit and two outpatient psychiatric clinics at an academic
      medical center. Two hundred forty individuals were approached to fill out the
      survey, of whom 200 (83.3%) did so. Forty-six percent of participants stated that
      they would put their own name onto the list. This novel suicide prevention
      proposal, a Do-Not-Sell List, would appeal to many people at high risk for
      suicide.

PMID- 27704598
TI  - Identification of sequence polymorphisms in the displacement loop region of
      mitochondrial DNA as a risk factor for gastroenteropancreatic neuroendocrine
      neoplasm.
AB  - BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are
      relatively rare tumors that arise from the diffuse neuroendocrine system, and the
      biggest advances in molecular biology have helped in understanding these
      biological diversity of tumors over the past decades. It is important to
      determine the carcinogenesis of GEP-NEN from the perspective of genetic
      backgrounds. METHODS: Mitochondrial DNA (mtDNA) of peripheral blood from 66 GEP
      NEN patients and from 75 healthy controls without history of any cancer were
      examined for single nucleotide polymorphisms (SNPs) and mutations in the
      displacement loop (D-loop) region. RESULTS: Single nucleotide polymorphisms were
      detected in 148 sites within the 982 bp mitochondria D-loop region from blood
      samples of healthy controls and GEP-NEN patients. SNPs with a rare allele
      frequency >5% in either controls or GEP-NEN patients were used for cancer risk
      analysis; a total of 23 SNPs were selected. When individual SNPs of GEP-NEN
      patients compared with healthy controls were analyzed, a statistically
      significant increase in the SNP frequency was observed for 73G, 150T, 151T, 492C,
      16257A, 16261T, and 16399G in GEP-NEN patients (P<.05). It was also observed that
      the SNP frequency for 489C and 16519C significantly decreased in GEP-NEN patients
      compared with controls (P<.05). CONCLUSION: In summary, SNPs in the mutations of
      the mitochondrial D-loop may be valuable markers for GEP-NEN risk evaluation.
      Analysis of the genetic polymorphisms in the D-loop may be useful for diagnosis
      of high-risk individuals.

PMID- 27704599
TI  - A zero-augmented generalized gamma regression calibration to adjust for covariate
      measurement error: A case of an episodically consumed dietary intake.
AB  - Measurement error in exposure variables is a serious impediment in
      epidemiological studies that relate exposures to health outcomes. In nutritional
      studies, interest could be in the association between long-term dietary intake
      and disease occurrence. Long-term intake is usually assessed with food frequency
      questionnaire (FFQ), which is prone to recall bias. Measurement error in FFQ
      reported intakes leads to bias in parameter estimate that quantifies the
      association. To adjust for bias in the association, a calibration study is
      required to obtain unbiased intake measurements using a short-term instrument
      such as 24-hour recall (24HR). The 24HR intakes are used as response in
      regression calibration to adjust for bias in the association. For foods not
      consumed daily, 24HR-reported intakes are usually characterized by excess zeroes,
      right skewness, and heteroscedasticity posing serious challenge in regression
      calibration modeling. We proposed a zero-augmented calibration model to adjust
      for measurement error in reported intake, while handling excess zeroes, skewness,
      and heteroscedasticity simultaneously without transforming 24HR intake values. We
      compared the proposed calibration method with the standard method and with
      methods that ignore measurement error by estimating long-term intake with 24HR
      and FFQ-reported intakes. The comparison was done in real and simulated datasets.
      With the 24HR, the mean increase in mercury level per ounce fish intake was about
      0.4; with the FFQ intake, the increase was about 1.2. With both calibration
      methods, the mean increase was about 2.0. Similar trend was observed in the
      simulation study. In conclusion, the proposed calibration method performs at
      least as good as the standard method.

PMID- 27704600
TI  - Reply to 'Endpoints in strategies to reduce polypharmacy'.

PMID- 27704602
TI  - Evaluation of the fundus in poorly dilating diabetic pupils using ultrawide field
      imaging.

PMID- 27704601
TI  - Comparing single-feeding and multi-feeding approaches for experimentally
      assessing trophic transfer of metals in fish.
AB  - Diet is an important pathway for metal uptake in marine organisms, and
      assimilation efficiency is one of the most relevant parameters to quantify
      trophic transfer of metals along aquatic food webs. The most commonly used method
      to estimate this parameter is pulse-chase feeding using radiolabeled food. This
      approach is, however, based on several assumptions that are not always tested in
      an experimental context. The present study aimed to validate the approach by
      assessing single-feeding and multiple-feeding approaches, using a model species
      (the turbot Scophthalmus maximus). Using the kinetic data obtained from the
      single-feeding experiment, the reconstruction of a multi-feeding experiment was
      tested for consistency with data provided by an actual multi-feeding performed
      under the same experimental conditions. The results validated the single-feeding
      approach. Environ Toxicol Chem 2017;36:1227-1234. (c) 2016 SETAC.

PMID- 27704603
TI  - Novel potential marker for native anteversion of the proximal femur.
AB  - Identifying native femoral version from proximal femoral landmarks would be of
      benefit both for preoperative assessment as well as intraoperatively. To identify
      potential markers for femoral anteversion, an empirical framework was developed
      for orientation-independent analysis of the proximal femur from pelvic CT to
      allow for segmentation of the proximal femur into five constituent regions:
      Femoral head, femoral neck, greater trochanter, lesser trochanter and femoral
      shaft. The framework is based on the identification of differences in the radius
      of curvature at anatomic zones of transition between regions of the proximal
      femur, followed by non-linear geometric shape fitting. The framework is applied
      to 86 proximal femurs segmented from pelvic CTs, with at least 2 cm of proximal
      femur remaining below the lesser trochanter, obtained for non-musculoskeletal
      pathology to investigate potential proximal femoral markers for native femoral
      version. The analysis of the proximal femur suggests a fixed relationship between
      the maximal femoral canal diameter 1 cm proximal to the base of the lesser
      trochanter from the center of the greater trochanter and the femoral neck axis of
      4.13 degrees  +/- 4.99 degrees . Further full-length femoral studies are needed
      to confirm the relationship of the maximal canal diameter as a proxy for native
      femoral anteversion. Published by Wiley Periodicals, Inc. J Orthop Res 35:1724
      1731, 2017.

PMID- 27704604
TI  - Early implant-associated osteomyelitis results in a peri-implanted bacterial
      reservoir.
AB  - Implant-associated osteomyelitis (IAO) is a common complication in orthopedic
      surgery. The aim of this study was to elucidate how deep IAO can go into the peri
      implanted bone tissue within a week. The study was performed in a porcine model
      of IAO. A small steel implant and either 104 CFU/kg body weight of Staphylococcus
      aureus or saline was inserted into the right tibial bone of 12 pigs. The animals
      were consecutively killed on day 2, 4 and 6 following implantation. Bone tissue
      around the implant was histologically evaluated. Identification of S. aureus was
      performed immunohistochemically on tissue section and with scanning electron
      microscopy and peptide nucleic acid in situ hybridization on implants. The
      distance of the peri-implanted pathological bone area (PIBA), measured
      perpendicular to the implant, was significantly larger in infected animals
      compared to controls (p = 0.0014). The largest differences were seen after 4 and
      6 days of inoculation, where PIBA measurements of up to 6 mm were observed.
      Positive S. aureus bacteria were identified on implants and from 25 MUm to 6 mm
      into PIBA. This is important knowledge for optimizing outcomes of surgical
      debridement in osteomyelitis.

PMID- 27704605
TI  - Granulomatous and lymphocytic hypophysitis - are they immunologically distinct?
AB  - Hypophysitis includes three histopathologically distinct entities -
      granulomatous, lymphocytic and xanthomatous forms. Etiopathogenesis and the
      immunological differences among these is not well characterized. This study aims
      to explore the immunopathogenesis of granulomatous and lymphocytic forms of
      hypophysitis. Demographic, clinical, endocrine function and radiological features
      of 33 histologically confirmed cases of hypophysitis were reviewed.
      Immunophenotyping of inflammatory component was performed in 13/33 cases. Visual
      disturbances (46%), headache (36%), polyuria/polydipsia (6%), menstrual
      disturbance (6%) and galactorrhoea (6%) were the frequent presenting symptoms.
      Endocrine abnormalities were noted in 11/18 cases evaluated (61%). Hypothyroidism
      was the most common endocrine abnormality (33.33%) followed by
      hyperprolactinaemia (22%) and hypocortisolism (16.66%). On neuroimaging, sellar
      mass with variable contrast enhancement was observed. On histology, granulomatous
      hypophysitis (GH) was more common (84.84%) than lymphocytic hypophysitis (LH)
      (15.15%). In GH, the infiltrate had almost equal proportions of CD3+ T cells and
      CD68+ histiocytes. Cytotoxic T cells (CD8+) predominated [CD4:CD8 < 1]. CD20+ B
      cell component ranged from <5% to 50%. Fibrosis, necrosis and giant cells
      accompanied GH. LH in contrast, had CD4+ T-helper cell predominance [CD4: CD8 >
      1]. CD68+ histiocytes constituted <20% and CD20+ B cells, 5-40% of the
      infiltrates. In conclusion, GH revealed cytotoxic T cell and histiocyte rich
      infiltrate in contrast to CD4+ T-cell predominance in LH suggesting that the two
      forms have distinct immunological mechanisms in evolution, an autoimmune process
      in LH and type IV hypersensitivity response in GH.

PMID- 27704606
TI  - Donor nerve sources in free functional gracilis muscle transfer for elbow flexion
      in adult brachial plexus injury.
AB  - BACKGROUND: With complete plexus injuries or late presentation, free functional
      muscle transfer (FFMT) becomes the primary option of functional restoration. Our
      purpose is to review cases over a 10-year period of free functioning gracilis
      muscle transfer after brachial plexus injury to evaluate the effect of different
      donor nerves used to reinnervate the FFMT on functional outcome. METHODS: A
      retrospective study from April 2001 to January 2011 of a single surgeon's
      practice was undertaken. During this time period 22 patients underwent FFMT at
      Washington University in St Louis, Missouri for elbow flexion. RESULTS: Thirteen
      patients for whom FFMT was performed for elbow flexion met all of the
      requirements for inclusion in this study. Average time from injury to first
      operation was 12.8 months (range 4-60), and average time from injury to FFMT was
      29 months (range 8-68). Average follow-up was 31.8 months (range 11-84). The
      nerve donors utilized included the distal accessory nerve, intercostal with or
      without rectus abdominis nerves, medial pectoral nerves, thoracodorsal nerve, and
      flexor carpi ulnaris fascicle of ulnar nerve. Functional recovery of elbow
      flexion was measured using the MRC grading system which showed 1 M5/5, 5 M4, 4
      M3, and 3 M2 outcomes. CONCLUSION: Intraplexal donor motor nerves if available
      will provide better transferred muscle function because they are higher quality
      donors closer to the muscle and can be done in one stage without a nerve graft.
      Otherwise, intercostal, rectus abdominis, or the distal accessory nerve should be
      used in a staged fashion. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:377
      382, 2017.

PMID- 27704608
TI  - Direct thrombectomy as a salvage technique in free flap breast reconstruction.
AB  - BACKGROUND: Breast reconstruction with microvascular free tissue transfer has
      become a widely used method. Despite a high rate of success, a compromised flap
      necessitating re-exploration can occur. Here, we introduce direct thrombectomy as
      a flap salvage technique, and compared the results with conventional
      thrombectomy. METHODS: A total of 488 patients who underwent breast
      reconstruction using a free transverse rectus abdominis myocutaneous flap between
      March 2009 and February 2014 were retrospectively analyzed. Flap salvage was
      conducted by either conventional thrombectomy using a Fogarty catheter, or direct
      thrombectomy via either a side branch or additional incisions at the stump of the
      main pedicle at the distal end of the thrombus. RESULTS: Flap compromise
      necessitating re-exploration due to extensive pedicle thrombosis was identified
      in 30 patients (6.1%). Direct thrombectomy was used in 9 patients, and
      conventional thrombectomy in 21 patients. Direct thrombectomy had a significantly
      higher success rate of flap salvage than conventional thrombectomy (88.9% vs.
      47.6%; P = .049). CONCLUSIONS: In the event of vascular thrombosis after free
      flap breast reconstruction, direct thrombectomy at the proximal pedicle stump
      beside the anastomosis opening appears to be an effective and reliable option
      that minimizes vessel trauma related to conventional catheter use. (c) 2016 Wiley
      Periodicals, Inc. Microsurgery 37:402-405, 2017.

PMID- 27704607
TI  - Deltamethrin toxicity and impaired swimming behavior of two backswimmer species.
AB  - Backswimmers (Hemiptera: Heteroptera: Notonectidae) are insect predators in a
      wide variety of freshwater habitats. These insects are well known through their
      role as mosquito biocontrol agents, their ability to prey on immature fishes and
      frogs, and because they are often the first to colonize aquatic habitats. As a
      consequence, these predators may face intended or unintended insecticide
      exposures that may lead to death or to impairment of essential behaviors (e.g.,
      swimming and position in the water column). The toxicity of deltamethrin (a type
      II pyrethroid insecticide stressor) and the swimming activity of the backswimmers
      Buenoa tarsalis and Martarega bentoi were evaluated. Concentration-mortality and
      survival bioassays were conducted with the insecticide, which were compared with
      controls without deltamethrin. Deltamethrin was 26-fold more toxic to B. tarsalis
      (median lethal concentration [LC50] = 4.0 ng a.i./L) than to M. bentoi (LC50 =
      102.5 ng a.i./L). The pattern of occupation of B. tarsalis, but not of M. bentoi,
      in the water column was also disrupted, and B. tarsalis was forced to stay near
      the water surface longer with exposure to deltamethrin. Thus, based on the
      findings, B. tarsalis was less resilient to deltamethrin exposure compared with
      M. bentoi, and the efficacy of swimming-dependent processes might be negatively
      affected (e.g., prey catching, partner encounter, and antipredator behaviors) for
      B. tarsalis under deltamethrin exposure. Environ Toxicol Chem 2017;36:1235-1242.
      (c) 2016 SETAC.

PMID- 27704609
TI  - The free medial sural artery perforator flap: Versatile option for soft tissue
      reconstruction in small-to-moderate size defects of the foot and ankle.
AB  - BACKGROUND: The medial sural artery perforator (MSAP) flap shows advantages for
      reconstruction in the foot and ankle, where bulk is a liability. We evaluated the
      versatility of this flap and provide further evidence on its use for covering
      small-to-moderate size defects by comparing the outcome depending on the region
      of reconstruction. METHODS: Twenty-two patients with variable defects of 4 * 4 to
      18 * 7 cm underwent MSAP flap reconstruction. Final outcomes of all patients were
      evaluated 12-months postoperatively using the AOFAS ankle-hindfoot, midfoot and
      hallux scale for clinical-functional evaluation, and the SF-36 health survey for
      quality-of-life measurement. The scores were compared in three groups according
      to the anatomic region of MSAP flap reconstruction. RESULTS: The flap size ranged
      between 6 * 4 and 21 * 9 cm. One venous congestion was salvaged by venous
      thrombectomy and reanastomosis, and one marginal flap necrosis healed by
      secondary intention. All flaps survived, and all patients returned to ambulation.
      Patients with reconstruction of the ankle-hindfoot or hallux showed significantly
      lower AOFAS ankle-hindfoot (P = 0.021) or hallux scores (P = 0.034), whereas
      reconstruction of the midfoot led to equal AOFAS midfoot scores (P = 0.265) as
      compared with patients without reconstruction in the respective region.
      Comparison of SF-36 physical (P = 0.936) and mental (P = 0.855) scores of all
      three regions remained insignificant. CONCLUSION: The MSAP flap provides thin
      soft tissue coverage, enabling good functional recovery after defect
      reconstruction all around the foot and ankle, with evident advantages in the
      midfoot. However, the functional outcomes after reconstruction of the ankle
      hindfoot or hallux region depend on the preexistent functional impairment.

PMID- 27704611
TI  - Variation in taper surface roughness for a single design effects the wear rate in
      total hip arthroplasty.
AB  - Material loss from the head-stem taper junction of total hip arthroplasty (THA)
      is implicated in adverse reactions to metal debris (ARMD); the mechanisms for
      this are multi-factorial. We investigated the relationship between the roughness
      of the "as manufactured" taper surface and the wear rate from this junction.
      Fifty retrieved Pinnacle metal-on-metal (MOM) bearings paired with a Corail stem
      were included in the study. Multivariable statistical analysis was performed to
      determine the influence of taper roughness on material loss rate after
      controlling for other confounding surgical, implant, and patient factors. The
      surface roughness of the "as manufactured" head taper surface was associated with
      the rate of material loss from this surface. Four of eighteen roughness variables
      taken from ISO 4,287 and ISO 13,565-2 were significant: The Reduced Peak Height
      (Rpk, the protruding peaks above the core) (p = 0.004), Material Ratio 1 (Mr1,
      the ratio of the protruding peaks above the core) (p = 0.002), Area of the Peak
      Region (A1, the area of the Abbott-Curve that contains the peaks from the
      profile) (p = 0.003) and the Skewness (Rsk, the asymmetry of the height
      distribution corresponding to the height or depth of surface features) (p =
      0.03). We found a large variability in the measured values with a median (range)
      of 0.50 (0.05-2.98), 11.98 (0.46-39.98), 30.89 (0.15-581.00), and 0.04 (-0.73
      0.84), respectively. A 1-unit increase in Rpk was associated with a 73% increase
      in the taper wear rate. The variability of "as manufactured" surface roughness
      has a significant effect on taper material loss. (c) 2016 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1784-1792, 2017.

PMID- 27704610
TI  - Phlyctenulosis: a systemic diagnosis made or missed in the blink of an eye.

PMID- 27704612
TI  - An alternative approach to combined autologous breast reconstruction with
      vascularized lymph node transfer.

PMID- 27704613
TI  - Percutaneous valve implantation in "tricuspid" position after a Fontan-Bjork
      operation.
AB  - BACKGROUND: A 30-year-old female with tricuspid valve atresia, ventricular septal
      defect, and atrial septal defect had a neonatal modified Blalock Taussig shunt
      and a Fontan-Bjork operation performed at five years of age. She did well
      initially but progressively developed signs of systemic congestion due to severe
      homograft stenosis and underwent successful percutaneous implantation of a
      Melody(r) pulmonary valve (Medtronic, Minneapolis, MN, USA) in the "tricuspid"
      position.

PMID- 27704614
TI  - Variation in food availability mediate the impact of density on cannibalism,
      growth, and survival in larval yellow spotted mountain newts (Neurergus
      microspilotus): Implications for captive breeding programs.
AB  - In this study, we examined cannibalistic behavior, growth, metamorphosis, and
      survival in larval and post-metamorph endangered yellow spotted mountain newts
      Neurergus microspilotus hatched and reared in a captive breeding facility. We
      designed a 2 * 2 factorial experiment, crossing two levels of food with two
      levels of density including high food/high density, high food/low density, low
      food/high density, and low food/low density. The level of cannibalistic behavior
      (including the loss of fore and hind limbs, missing toes, tail, gills, body
      damage, and whole body consumption) changed as the larvae grew, from a low level
      during the first 4 weeks, peaking from weeks 7 to 12, and then dropped during
      weeks 14-52. Both food level and density had a significant effect on cannibalism.
      The highest frequency of cannibalism was recorded for larvae reared in the low
      food/high density and lowest in high food/low density treatments. Growth, percent
      of larval metamorphosed, and survival were all highest in the high food/low
      density and lowest in low food/high density treatment. Food level had a
      significant effect on growth, metamorphosis, and survival. However, the two
      levels of density did not influence growth and metamorphosis but showed a
      significant effect on survival. Similarly, combined effects of food level and
      density showed significant effects on growth, metamorphosis, and survival over
      time. Information obtained from current experiment could improve productivity of
      captive breeding facilities to ensure the release of adequate numbers of
      individuals for reintroduction programs. Zoo Biol. 35:513-521, 2016. (c) 2016 The
      Authors. Zoo Biology published by Wiley Periodicals, Inc.

PMID- 27704615
TI  - Role of Runx2 polymorphisms in risk and prognosis of ossification of posterior
      longitudinal ligament.
AB  - BACKGROUND: Our study was aimed at finding out if Runx2 SNPs (single-nucleotide
      polymorphisms) are related to susceptibility to and prognosis of ossification of
      posterior longitudinal ligament (OPLL). METHODS: We selected 80 OPLL patients and
      another 80 independent patients without OPLL from September 2013 to November
      2014. Serum was collected to detect the genotypes of rs1321075, rs12333172, and
      rs1406846 on Runx2 with direct sequencing analysis. RESULTS: Differences in
      clinical characteristics, including age, weight, height, sex ratio, as well as
      smoking and drinking history, between OPLL and control groups appeared to be
      insignificant (all P-value >.05). The allele of rs1406846 (A) emerged as a key
      element in raising OPLL risk with the biggest statistical significance (P<.001).
      Conversely, alleles of rs967588 (T) and rs16873379 (C) were associated with
      reduced predisposition to OPLL less remarkably (both P=.033). Regarding
      rs16873379, the case group exhibited a smaller frequency of homozygote CC in
      comparison with TT genotype than the control group (P=.016). Furthermore, the
      improvement rate based on calculation of JOA score suggested that genotype AA of
      rs6908650 was beneficial for OPLL patients' recovery from posterior laminoplasty
      surgery (P<.05), while genotypes of rs16873379 (CC), rs1406846 (AA), and
      rs2677108 (CC) significantly restrained this process (P<.05). Besides,
      rs16873379, rs1406846, and rs2677108 were significantly associated with number of
      ossification segments (P<.05). CONCLUSIONS: Runx2 SNPs (e.g., rs16873379,
      rs1406846, and rs2677108) were strongly correlated with onset and treatment
      efficacy of OPLL, and they might regulate severity of OPLL.

PMID- 27704616
TI  - Anatomical and functional correlates of persistent pain in Parkinson's disease.
AB  - BACKGROUND: The pathophysiology of pain in Parkinson's disease (PD) is still
      poorly understood, although it is conceivable that supraspinal mechanisms may be
      responsible for pain generation and maintenance. METHODS: We examined brain
      functional and anatomical changes associated with persistent pain in 40 PD
      patients, 20 with persistent pain and 20 without pain. We also examined 15 pain
      free healthy participants of similar age, gender, and cognitive state as a
      control group. We assessed pain by the King's Parkinson's Pain Scale, the Visual
      Analogue Scale for pain, and the Leeds Assessment for Neuropathic Symptoms and
      Sign. All patients underwent structural, diffusion tensor imaging, and resting
      state functional MRI. We compared clinical characteristics, whole-brain cortical
      thickness, subcortical volumes, diffusion tensor imaging scalar measures, and
      functional connectivity by network based statistics. RESULTS: The group with PD
      and persistent pain showed significant thinning in the bilateral temporal pole,
      left-medial orbitofrontal cortex, bilateral superior and left-inferior parietal
      areas, pars orbicularis, and right superior frontal, posterior cingulated, and
      precentral cortex. There were no significant subcortical volume and white matter
      differences between PD subgroups. Functional MRI showed a decrease of brain
      activity in the left frontal inferior orbital in PD patients with persistent
      pain, with greater activity bilaterally in the cerebellum and in the right
      inferior temporal areas. Only PD patients with persistent pain showed an
      accumbens-hippocampus disconnection without white matter and subcortical
      alterations. CONCLUSIONS: We showed that persistent pain in PD is associated with
      supraspinal structural and functional changes. We also highlighted the
      contribution of frontal, prefrontal, and insular areas in nociceptive modulation
      and accumbens-hippocampus disconnection. (c) 2016 International Parkinson and
      Movement Disorder Society.

PMID- 27704618
TI  - Care to share?

PMID- 27704617
TI  - Netazepide, a gastrin/cholecystokinin-2 receptor antagonist, can eradicate
      gastric neuroendocrine tumours in patients with autoimmune chronic atrophic
      gastritis.
AB  - AIMS: Netazepide, a gastrin/cholecystokinin 2 receptor antagonist, once daily for
      12 weeks reduced the number of tumours and size of the largest one in 16 patients
      with autoimmune chronic atrophic gastritis (CAG), achlorhydria, hypergastrinaemia
      and multiple gastric neuroendocrine tumours (type 1 gastric NETs), and normalized
      circulating chromogranin A (CgA) produced by enterochromaffin-like cells, the
      source of the tumours. The aim was to assess whether longer-term netazepide
      treatment can eradicate type 1 gastric NETs. METHODS: After a mean 14 months off
      netazepide, 13 of the 16 patients took it for another 52 weeks. Assessments were:
      gastroscopy; gene-transcript expression in corpus biopsies using quantitative
      polymerase chain reaction; blood CgA and gastrin concentrations; and safety
      assessments. RESULTS: While off-treatment, the number of tumours, the size of the
      largest one, and CgA all increased again. Netazepide for 52 weeks: cleared all
      tumours in 5 patients; cleared all but one tumour in one patient; reduced the
      number of tumours and size of the largest one in the other patients; normalized
      CgA in all patients; and reduced mRNA abundances of CgA and histidine
      decarboxylase in biopsies. Gastrin did not increase further, confirming that the
      patients had achlorhydria. Netazepide was safe and well tolerated. CONCLUSIONS: A
      gastrin/cholecystokinin 2 receptor antagonist is a potential medical and targeted
      treatment for type 1 gastric NETs, and an alternative to regular gastroscopy or
      surgery. Treatment should be continuous because the tumours will regrow if it is
      stopped. Progress can be monitored by CgA in blood or biomarkers in mucosal
      biopsies.

PMID- 27704619
TI  - The contribution of policy, law, management, research, and advocacy failings to
      the recent extinctions of three Australian vertebrate species.
AB  - Extinctions typically have ecological drivers, such as habitat loss. However,
      extinction events are also influenced by policy and management settings that may
      be antithetical to biodiversity conservation, inadequate to prevent extinction,
      insufficiently resourced, or poorly implemented. Three endemic Australian
      vertebrate species-the Christmas Island pipistrelle (Pipistrellus murrayi),
      Bramble Cay melomys (Melomys rubicola), and Christmas Island forest skink (Emoia
      nativitatis)-became extinct from 2009 to 2014. All 3 extinctions were predictable
      and probably preventable. We sought to identify the policy, management, research,
      and other shortcomings that contributed to their extinctions or failed to prevent
      them. These included a lack within national environmental legislation and policy
      of explicit commitment to the prevention of avoidable extinctions, lack of
      explicit accountability, inadequate resources for conservation (particularly for
      species not considered charismatic or not of high taxonomic distinctiveness),
      inadequate biosecurity, a slow and inadequate process for listing species as
      threatened, recovery planning that failed to consider the need for emergency
      response, inability of researchers to identify major threatening factors, lack of
      public engagement and involvement in conservation decisions, and limited
      advocacy. From these 3 cases, we recommend: environmental policy explicitly seeks
      to prevent extinction of any species and provides a clear chain of accountability
      and an explicit requirement for public inquiry following any extinction;
      implementation of a timely and comprehensive process for listing species as
      threatened and for recovery planning; reservation alone not be assumed sufficient
      to maintain species; enhancement of biosecurity measures; allocation of
      sufficient resources to undertake actions necessary to prevent extinction;
      monitoring be considered a pivotal component of the conservation response;
      research provides timely identification of factors responsible for decline and of
      the risk of extinction; effective dissemination of research results; advocacy by
      an informed public for the recovery of threatened species; and public involvement
      in governance of the recovery process. These recommendations should be applicable
      broadly to reduce the likelihood and incidence of extinctions.

PMID- 27704620
TI  - The impact of vascular endothelial growth factor +405 C/G polymorphism on long
      term outcome and severity of coronary artery disease.
AB  - BACKGROUND: The association between genetic variations of vascular endothelial
      growth factor (VEGF) gene and the risk for atherosclerosis has been hypothesized.
      We aimed to assess the relationship between rs2010963 (+405 C/G) polymorphism and
      presence, severity, and outcome of coronary artery disease (CAD) in an Iranian
      cohort. METHODS: Genotyping of VEGF rs2010963 polymorphism was performed on 520
      individuals, comprising 347 patients with documented coronary artery disease
      based on angiography report and 173 individuals with normal coronary arteries,
      using the TaqMan real-time PCR method. In final, 484 subjects were followed up
      over a 5-year period for cardiovascular-related outcomes. RESULTS: C allele of
      VEGF rs2010963 polymorphism was related to increase risk for CAD and also
      slightly to 5-year cardiovascular mortality. The 5-year survival in C and G
      allele subgroups were 92.3% and 94.3% in CAD group and 95.7% and 98.0% in non-CAD
      group, respectively. CONCLUSIONS: Vascular endothelial growth factor rs2010963
      polymorphism may be associated with the presence of CAD and its long-term
      survival, but not with its severity. To the best of our knowledge, this is the
      first report of genetic association between rs2010963 SNP and CAD-related death.
      It can be thus suggested that rs2010963 VEGF gene can be considered as a genetic
      risk predictor for CAD and its outcomes.

PMID- 27704621
TI  - High School CPR/AED Training in Washington State.
AB  - OBJECTIVE: Describe the rates of CPR/AED training in high schools in the state of
      Washington after passage of legislation mandating CPR/AED training. DESIGN AND
      SAMPLE: A web-based survey was sent to administrators at 660 public and private
      high schools in the state of Washington. RESULTS AND CONCLUSIONS: The survey was
      completed by 148 schools (22%); 64% reported providing CPR training and 54%
      provided AED training. Reported barriers to implementation included instructor
      availability, cost, and a lack of equipment. Descriptive statistics were used to
      describe the sample characteristics and implementation rates. Mandates without
      resources and support do not ensure implementation of CPR/AED training in high
      schools. Full public health benefits of a CPR mandate will not be realized until
      barriers to implementation are identified and eliminated through use of
      available, accessible public health resources.

PMID- 27704622
TI  - The human gastrointestinal tract and oral microbiota in inflammatory bowel
      disease: a state of the science review.
AB  - Inflammatory bowel disease (IBD) includes a spectrum of diseases from ulcerative
      colitis (UC) to Crohn's disease (CD). Many studies have addressed the changes in
      the microbiota of individuals affected by UC and CD. A decrease in biodiversity
      and depletion of the phyla Bacteroidetes and Firmicutes has been reported, among
      others. Changes in microbial composition also result in changes in the
      metabolites generated in the gut from microbial activity that may involve the
      amount of butyrate and other metabolites such as H2 S being produced. Other
      factors such as diet, age, or medication need to be taken into consideration when
      studying dysbiosis associated with IBD. Diverse bacterial species have been
      associated specifically or non-specifically to IBD, but none of them have been
      demonstrated to be its ethiological agent. Recent studies also suggest that micro
      eukaryotic populations may also be altered in IBD patients. Last, but not least,
      viruses, and specially bacteriophages, can play a role in controlling microbial
      populations in the gastrointestinal tract. This may affect both bacterial
      diversity and metabolism, but possible implications for IBD still remain to be
      solved. Dysbiosis in the oral microbiome associated with IBD remains an emerging
      field for future research.

PMID- 27704623
TI  - Reply to: Challenges in the Acquisition and Analysis of Bone Microstructure
      During Growth.

PMID- 27704625
TI  - Single molecule mass measurements and mass spectrometry.

PMID- 27704624
TI  - Extended locoregional use of intercostal artery perforator propeller flaps.
AB  - Besides conventional flaps, intercostal artery perforator flaps have been
      reported to cover trunk defects. In this report the use of anterior intercostal
      artery perforator (AICAP) flap, lateral intercostal artery perforator (LICAP)
      flap and dorsal intercostal artery perforator (DICAP) flap for thoracic,
      abdominal, cervical, lumbar and sacral defects with larger dimensions and
      extended indications beyond the reported literature were reevaluated. Thirty-nine
      patients underwent surgery between August 2012 and August 2014. The age of the
      patients ranged between 16 and 79 with a mean of 49 years. The distribution of
      defects were as follows; 12 thoracic, 8 parascapular, 3 cervical, 8 abdominal, 4
      sacral and 4 lumbar. AICAP, LICAP and DICAP flaps were used for reconstruction.
      Fifty-two ICAP flaps were performed on 39 patients. Flap dimensions ranged
      between 6 * 9 cm and 14 * 35 cm. Twenty-six patients had single flap coverage and
      13 patients had double flap coverage. Forty-six flaps have been transferred as
      propeller flaps and 6 flaps have been transferred as perforator plus flap. Forty
      flaps (75%) went through transient venous congestion. In one DICAP flap, 30% of
      flap was lost. No infection, hematoma or seroma were observed in any patient.
      Follow-up period ranged between 3 and 32 months with a mean of 9 months. The ICAP
      flaps provide reliable and versatile options in reconstructive surgery and can be
      used for challenging defects in trunk.

PMID- 27704626
TI  - The Me3 NB12 Cl11. Radical: A Strong One-Electron Oxidizing Agent.
AB  - Strong oxidizing agents often contain fluorine and are not compatible with
      substrates forming strong element-fluorine bonds. Therefore, there is need for
      new strong oxidizers. Cyclic voltammetric measurements on the weakly coordinating
      anion [Me3 NB12 Cl11 ]- in liquid SO2 revealed an oxidation wave at +2.59 V
      versus Fc0/+ . The oxidation of Na[Me3 NB12 Cl11 ] with AsF5 in liquid sulfur
      dioxide gives the boron-cluster-based radical Me3 NB12 Cl11. as a dark blue solid
      in quantitative yield. The radical was characterized by vibrational, NMR, and EPR
      spectroscopy and by its crystal structure. To explore the potential of the
      radical Me3 NB12 Cl11. to act as a strong oxidizing agent, it was reacted with
      different compounds having high ionization energies. Thianthrene (ionization
      energy 7.8 eV) and hexabromobenzene (8.8 eV) were oxidized to the corresponding
      cations. The reaction with elemental iodine (9.3 eV) gave the [I5 ]+ cation.
      These reactive cations are stabilized in the solid state by the weakly
      coordinating anion [Me3 NB12 Cl11 ]- , which was formed as a reduced product in
      the oxidation reactions.

PMID- 27704627
TI  - Up-regulation of microRNA-491-5p suppresses cell proliferation and promotes
      apoptosis by targeting FOXP4 in human osteosarcoma.
AB  - BACKGROUND AND OBJECTIVES: MicroRNAs are small non-coding RNAs involved in
      pathogenesis and progression of human malignancies. MicroRNA-491-5p (miR-491-5p)
      is down-regulated in many human cancers where it would serve as a tumour
      suppressor. However, the role played by miR-491-5p in pathogenesis of human
      osteosarcoma has remained largely unknown. This study has been conducted to
      examine effects of miR-491-5p on migration and proliferation of cells of the SAOS
      2 and MG63 osteosarcoma lines, and mechanisms of those effects. MATERIALS AND
      METHODS: Levels of miR-491-5p expression in osteosarcoma tissues and in human
      osteosarcoma cell lines were studied using qualitative real-time polymerase chain
      reaction (qRT-PCR) methods. Cell viability was detected using the CCK-8 and EdU
      assays, while the transwell assay was used to evaluate migration and invasion.
      Apoptosis was analysed uing flow cytometry and the Hoechst 33342 nuclear staining
      method. A dual-luciferase reporter system was used to confirm the target gene of
      miR-491-5p. The electrophoretic mobility shift assay (EMSA) with DIG-labelled
      double-stranded FOXP4 oligonucleotides was used to confirm whether or not miR-491
      5p suppressed FOXP4 activation. RESULTS: Cells of osteosarcoma tissues and cell
      lines had low levels of miR-491-5p expression, but high levels of forkhead-box P4
      (FOXP4) expression. Transfection of SAOS-2 and MG63 cells with miR-491-5p mimics
      inhibited expression of FOXP4 protein, which suppressed cell growth and
      migration, but induced apoptosis. Dual-luciferase reporter assays confirmed FOXP4
      as the target gene for miR-491-5p. Overexpression of miR-491-5p suppressed FOXP4
      activity in SAOS-2 and MG63 cells. Knockdown of FOXP4 in SAOS-2 and MG63 cells
      using an RNAi strategy resulted in reduced levels of cell proliferation and
      migration, but increased levels of apoptosis. CONCLUSION: Our in vitro studies
      showed that up-regulation of miR-491-5p suppressed proliferation of the human
      osteosarcoma cells and induced apoptosis by targeting FOXP4. These findings
      suggest that miR-491-5p could be further studied as a potential clinical
      diagnostic or predictive biomarker for human osteosarcoma.

PMID- 27704628
TI  - Effects of 12-week resistance training during radiotherapy in breast cancer
      patients.
AB  - Exercise is considered to be an effective supportive treatment approach in breast
      cancer (BC) patients. We conducted a randomized controlled trial to assess the
      efficacy of a 12-week PRT during radiotherapy. Strength performance was assessed
      by maximal isokinetic peak torque (MIPT) in two different angular velocities (60
      degrees /s and 180 degrees /s) and maximal voluntary isometric contraction for
      shoulder external and internal rotation, as well as for knee extension and
      flexion were assessed pre- and post-intervention in 146 patients randomized to
      PRT or a control group. Statistical analyses were based on analysis of covariance
      models for the individual changes from baseline to week 13. Intention-to-treat
      analyses showed significant between-group differences favoring the exercise group
      (EX) for MIPT in knee flexion and shoulder internal and external rotation (P <
      0.05). Subgroup analyses showed borderline significant differences with regard to
      pretreatment history, revealing that pretreated chemotherapy patients tend to
      benefit more from PRT than patients without chemotherapy (P = 0.06). Strength
      gain at the operated arm was significantly higher than at the non-operated arm in
      EX. PRT was efficacious in increasing upper and lower limb strength in BC
      patients undergoing adjuvant radiotherapy. Patients with restrictions due to
      breast cancer-related surgery and pretreated with chemotherapy might benefit the
      most.

PMID- 27704629
TI  - Fusobacterium necrophorum findings in Denmark from 2010 to 2014 using data from
      the Danish microbiology database.
AB  - Fusobacterium necrophorum findings in Denmark and estimation of the incidence of
      F. necrophorum bacteraemia was described using data from the nationwide Danish
      microbiology database (MiBa). All microbiological reports on any Fusobacterium
      species in Denmark were extracted for a period of 5 years from 2010 to 2014 from
      MiBa and from the local department of clinical microbiology. The overall
      incidence of F. necrophorum bacteraemia from 2010 to 2014 was 2.8 cases per
      million/year vs 9.4 in the age group 15-24 years. F. necrophorum was rare in
      blood cultures from children and middle-aged patients and then raised again.
      However, 48 of 232 cases of Fusobacterium bacteraemia were not identified to
      species level, so the incidences of F. necrophorum bacteraemia may be
      underestimated in our study. F. necrophorum was found in throat swabs in the age
      group between 13 and 40 years and in otitis media in children below 2 years in
      those departments which performed anaerobic culture. The incidence of F.
      necrophorum bacteraemia found was comparable to earlier reported figures for
      Lemierre's syndrome. Fusobacterium bacteraemia should always be identified to
      species level.

PMID- 27704632
TI  - Current and emerging therapies in premature ejaculation: Where we are coming
      from, where we are going.
AB  - Premature ejaculation is the most common form of sexual dysfunction among men.
      The pathophysiology of premature ejaculation appears to be multifactorial,
      implicating the need for multimodal therapeutic regimens to successfully treat
      premature ejaculation. Multiple treatment regimens have been shown to be
      effective in extending the time between penetration and ejaculation. These
      treatment modalities include everything from behavioral modifications and
      medications to diet alterations and major surgery. The goal of the present
      article was to review the commonly used treatment regimens used in the treatment
      of premature ejaculation, as well as to introduce and discuss the newest
      treatment routines under study for the treatment of premature ejaculation.

PMID- 27704630
TI  - Genetic architecture of motives for leisure-time physical activity: a twin study.
AB  - The aim of this study was to estimate the contribution of genetic and
      environmental influences on motives for engaging in leisure-time physical
      activity. The participants were obtained from the FinnTwin16 study. A modified
      version of the Recreational Exercise Motivation Measure was used to assess the
      motives for leisure-time physical activity in 2542 twin individuals (mean age of
      34.1 years). Linear structural equation modeling was used to investigate the
      genetic and environmental influences on motive dimensions. The highest
      heritability estimates were found for the motive dimensions of "enjoyment" [men
      33% (95% CI 23-43%), women 53% (95% CI 45-60%)] and "affiliation" [men 39% (95%
      CI 0.28-0.49%), women 35% (95% CI 0.25-0.43%)]. The lowest heritability estimates
      were found for others' expectations [men 13% (95% CI 0.04-0.25%), women 15% (95%
      CI 0.07-0.24%)]. Unique environmental influences explained the remaining
      variances, which ranged from 47% to 87%. The heritability estimates for summary
      variables of intrinsic and extrinsic motives were 36% and 32% for men and 40% and
      24% for women, respectively. In conclusion, genetic factors contribute to motives
      for leisure-time physical activity. However, the genetic effects are, at most,
      moderate, implying the greater relative role of environmental factors.

PMID- 27704631
TI  - Oral spray wintertime vitamin D3 supplementation has no impact on inflammation in
      Gaelic footballers.
AB  - Vitamin D inadequacy [total 25(OH)D <50 nmol/L] is widespread in athletes. The
      biologically active metabolite, 1,25-dihydroxyvitamin D, may be involved in
      regulating inflammation although in vitro findings have not been consistently
      replicated in human intervention trials. This study, conducted at a latitude of
      55 degrees N, aimed to assess inflammatory biomarkers in Gaelic footballers
      before and after a wintertime vitamin D3 intervention. Samples from a 12-week
      double-blind, randomized, placebo-controlled trial, in which 42 Gaelic
      footballers received 3000 IU (75 MUg) vitamin D3 daily or placebo via oral spray
      solutions, were analysed for a range of inflammatory biomarkers. Cytokines
      (interleukin-8 and tumor necrosis factor-alpha), cathelicidin and high
      sensitivity C-reactive protein were quantified by multiplex assay, enzyme-linked
      immunosorbent assay and clinical biochemistry, respectively. White blood cell,
      lymphocyte, and neutrophil concentrations were determined by full blood profile.
      Data on total 25-hydroxyvitamin D, measured by LC-MS/MS, were available from the
      previous study. Vitamin D3 supplementation significantly increased mean total 25
      hydroxyvitamin D concentrations from 47 to 84 nmol/L (P = 0.006); yet this had no
      effect on white blood cell count (P = 0.699), lymphocyte (P = 0.694), neutrophil
      (P = 0.594), interleukin-8 (P = 0.334), tumor necrosis factor-alpha (P = 0.587),
      cathelicidin (P = 0.745) or high sensitivity C-reactive protein concentration (P
      = 0.621) compared to placebo. 12-weeks vitamin D3 supplementation did not impact
      the immune profile of Gaelic footballers. This is likely because biomarkers were
      within their respective normal range or at a concentration similar to that of the
      general population at baseline. Future studies are encouraged to use inflammation
      as their primary outcome measure and recruit athletes at risk of compromised
      immunity.

PMID- 27704633
TI  - Plants as Antileishmanial Agents: Current Scenario.
AB  - Leishmaniasis is a clinical manifestation caused by the parasites of the genus
      Leishmania. Plants are reservoirs of bioactive compounds, which are known to be
      chemically balanced, effective and least injurious as compared with synthetic
      medicines. The current resistance and the toxic effects of the available drugs
      have brought the trend to assess the antileishmanial effect of various plant
      extracts and their purified compound/s, which are summarized in this review.
      Moreover, it also highlights various traditional remedies used by local healers
      against leishmaniasis. A systematic cross-sectional study for antileishmanial
      activity of natural products was carried out using multiple literature databases.
      The records retrieved since 2000 till year 2016 were analysed and summarized in
      the form of comprehensive tables and graphs. Natural products are potential
      source of new and selective agents that can significantly contribute to primary
      healthcare and probably are promising substitutes of chemicals for the treatment
      of protozoan diseases like leishmaniasis. Where the researchers prefer to use
      alcoholic solvents for the extraction of antileishmanial agents from plants, most
      of the studies are limited to in vitro conditions majorly on using promastigote
      forms of Leishmania. Thus, there is a need to carry out such activities in vivo
      and in host macrophages. Further, there is a need of mechanistic studies that can
      help taking few of the promising pure compounds to clinical level. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27704634
TI  - Advancement of the Subjective Vitality Scale: examination of alternative
      measurement models for Japanese and Singaporeans.
AB  - The Subjective Vitality Scale (SVS: Ryan & Frederick, 1997) is a 7-item self
      report instrument to measure one's level of vitality and has been widely used in
      psychological studies. However, there have been discrepancies in which version of
      the SVS (7- or 6-item version) employed between as well as within researchers.
      Moreover, Item 5 seems not be a good indicator of vitality from a content
      validity perspective. Therefore, the present study aimed to evaluate the validity
      and reliability of the SVS for Japanese and Singaporeans rigorously by comparing
      3 measurement models (5-, 6-, and 7-item models). To this end, the scale was
      first translated from English to Japanese and then the Japanese and English
      versions of the scale were administered to Japanese (n = 268) and Singaporean
      undergraduate students (n = 289), respectively. The factorial and concurrent
      validity of the three models were examined independently on each of the samples.
      Furthermore, the covariance stability of the vitality responses was assessed over
      a 4-week time period for another independent Japanese sample (n = 140). The
      findings from this study indicated that from methodological and content validity
      perspectives, the 5-item model is considered most preferable for both language
      versions of the SVS.

PMID- 27704635
TI  - Spontaneous cryptococcal peritoneal effusion: an unusual cytological diagnosis
      with a poor prognosis.

PMID- 27704636
TI  - Expression of Epstein-Barr virus among oral potentially malignant disorders and
      oral squamous cell carcinomas in the South Indian tobacco-chewing population.
AB  - BACKGROUND: Oral cancer is the sixth most common malignancy in the world. Viruses
      are the causative agents of approximately 10-15% of all cancers worldwide
      (Cancers, 6, 2014 and 2155). The tumorigenic roles of Epstein-Barr virus in oral
      cancer are unclear. Literature search results are conflicting and dependent on
      various factors such as geographical/regional variations, sociocultural
      lifestyles, dietary habits, chewing/smoking tobacco habit. This study is the
      first original observation about frequency of Epstein-Barr virus among South
      Indian tobacco-chewing patients to elucidate its involvement in oral
      carcinogenesis and to know whether this can be a valuable diagnostic and
      prognostic indicator. MATERIALS AND METHODS: A total number of 75 tobacco chewer
      subjects aged between 23 and 76 years with histopathologically confirmed oral
      potentially malignant disorders (25), oral squamous cell carcinoma (25), and age
      matched healthy controls (25) formed the study group. Immunohistochemical
      expression of Epstein-Barr virus latent membrane protein 1 was assessed among
      cases and healthy controls. RESULTS: Out of the total 75 subjects, six subjects
      (8%) were positive for Epstein-Barr virus antigen and 69 subjects (92%) negative.
      The antigen positivity was observed among two cases of moderately differentiated
      oral squamous cell carcinoma, two cases of leukoplakia, and two healthy controls.
      CONCLUSION: No significant association between Epstein-Barr virus positivity was
      observed among oral potentially malignant disorders and oral squamous cell
      carcinoma among South Indian tobacco-chewing patients. This can be partially
      explained by the methodology employed, by the patient population analyzed and
      different habits in various geographical regions.

PMID- 27704637
TI  - Retrospective analysis of in vivo recovery and clearance during continuous
      infusion of recombinant factor VIII products: a single-institution study.
AB  - BACKGROUND: Continuous infusion (CI) of recombinant FVIII (rFVIII) concentrates
      has been reported as an effective and safe method to achieve haemostasis during
      major surgeries or severe bleeding events. For more effective and safer CI,
      better understanding of in vivo recovery (IVR) and clearance (CL) issues is
      imperative. OBJECTIVE: We investigated the following factors affecting IVR and CL
      using univariate and multivariate regression analyses during 47 CIs in 34
      patients: rFVIII concentrate type, haemophilia severity, blood type, the presence
      of hepatitis C virus (HCV) or human immunodeficiency virus (HIV), age and body
      mass index (BMI). RESULTS: The mean IVR was 1.64 +/- 0.49 IU dL-1 per IU kg-1 ,
      and the mean CL during CI was 3.56 +/- 1.57 mL h-1 kg-1 . The univariate and
      multivariate regression analyses showed that the CL of octocog alfa was
      significantly lower than that of rurioctocog alfa (P = 0.043 and 0.0034,
      respectively). There was a significant difference in BMI in the univariate and
      multivariate regression analyses (P = 0.0403 and 0.0376, respectively).
      CONCLUSIONS: This study indicated that CL during CI was potentially affected by
      the type of rFVIII concentrate used and BMI.

PMID- 27704638
TI  - Control of Bone Anabolism in Response to Mechanical Loading and PTH by Distinct
      Mechanisms Downstream of the PTH Receptor.
AB  - Osteocytes integrate the responses of bone to mechanical and hormonal stimuli by
      poorly understood mechanisms. We report here that mice with conditional deletion
      of the parathyroid hormone (PTH) receptor 1 (Pth1r) in dentin matrix protein 1
      (DMP1)-8kb-expressing cells (cKO) exhibit a modest decrease in bone resorption
      leading to a mild increase in cancellous bone without changes in cortical bone.
      However, bone resorption in response to endogenous chronic elevation of PTH in
      growing or adult cKO mice induced by a low calcium diet remained intact, because
      the increased bone remodeling and bone loss was indistinguishable from that
      exhibited by control littermates. In contrast, the bone gain and increased bone
      formation in cancellous and cortical bone induced by daily injections of PTH and
      the periosteal bone apposition induced by axial ulna loading were markedly
      reduced in cKO mice compared to controls. Remarkably, however, wild-type (WT)
      control littermates and transgenic mice overexpressing SOST injected daily with
      PTH exhibit similar activation of Wnt/beta-catenin signaling, increased bone
      formation, and cancellous and cortical bone gain. Taken together, these findings
      demonstrate that Pth1r in DMP1-8kb-expressing cells is required to maintain basal
      levels of bone resorption but is dispensable for the catabolic action of chronic
      PTH elevation; and it is essential for the anabolic actions of daily PTH
      injections and mechanical loading. However, downregulation of Sost/sclerostin,
      previously shown to be required for bone anabolism induced by mechanical loading,
      is not required for PTH-induced bone gain, showing that other mechanisms
      downstream of the Pth1r in DMP1-8kb-expressing cells are responsible for the
      hormonal effect. (c) 2016 American Society for Bone and Mineral Research.

PMID- 27704639
TI  - Modelling hospital length of stay using convolutive mixtures distributions.
AB  - Length of hospital stay (LOS) is an important indicator of the hospital activity
      and management of health care. The skewness in the distribution of LOS poses
      problems in statistical modelling because it fails to adequately follow the usual
      traditional distribution of positive variables such as the log-normal
      distribution. We present in this paper a model using the convolution of two
      distributions, a technique well known in the signal processing community. The
      specificity of that model is that the variable of interest is considered to be
      the resulting sum of two random variables with different distributions. One of
      the variables features the patient-related factors in terms of their need to
      recover from their admission condition, while the other models the hospital
      management process such as the discharging process. Two estimation procedures are
      proposed. One is the classical maximum likelihood, while the other relates to the
      expectation-maximization algorithm. We present some results obtained by applying
      this model to a set of real data from a group of hospitals in Victoria
      (Australia). Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27704640
TI  - Vertical augmentation of the posterior atrophic mandible by interpositional
      grafts in a split-mouth design: a human tomography evaluation pilot study.
AB  - OBJECTIVE: Using computed tomography, to compare vertical and volumetric bone
      augmentation after interposition grafting with bovine bone mineral matrix
      (GEISTLICH BIO-OSS(r) ) or hydroxyapatite/tricalcium phosphate (STRAUMANN(r)
      BONECERAMIC) for atrophic posterior mandible reconstruction through segmental
      osteotomy. MATERIAL AND METHODS: Seven patients received interposition grafts in
      the posterior mandible for implant rehabilitation. The computed tomography cone
      beam images were analysed with OsiriX Imaging Software 6.5 (Pixmeo Geneva,
      Switzerland) in the pre-surgical period (T0), at 15 days post-surgery (T1) and at
      180 days post-surgery (T2). The tomographic analysis was performed by a single
      trained and calibrated radiologist. Descriptive statistics and nonparametric
      methods were used to analyse the data. RESULTS: There was a significant
      difference in vertical and volume augmentation with both biomaterials using the
      technique (P < 0.05). There were no significant differences (P > 0.05) in volume
      change of the graft, bone volume augmentation, or augmentation of the maximum
      linear vertical distance between the two analysed biomaterials. CONCLUSIONS: The
      GEISTLICH BIO-OSS(r) and STRAUMANN(r) BONECERAMIC interposition grafts exhibited
      similar and sufficient dimensional stability and volume gain for short implants
      in the atrophic posterior mandible.

PMID- 27704642
TI  - Enhanced Stability of Perovskite Solar Cells through Corrosion-Free Pyridine
      Derivatives in Hole-Transporting Materials.
AB  - The molecular structure of pyridine derivatives is critical to perovskite solar
      cell performance, especially stability. Most of the pyridine additives easily
      form complexes with perovskite. A new pyridine additive with a long alkyl chain
      substituted at its o-position does not corrode perovskite. The stability of
      devices containing this additive is the highest among the investigated cells.

PMID- 27704641
TI  - Parametrial involvement in women with low-risk, early-stage cervical cancer.
AB  - This study identified the incidence of parametrial involvement in low risk, early
      stage cervical cancer patients and evaluated the factors associated with
      parametrial involvement. All stage IA2-IB1 cervical cancer patients who underwent
      radical hysterectomy with pelvic lymphadenectomy were retrospectively reviewed.
      Patients with squamous cell carcinoma or adenocarcinoma grade 1-2, tumour size
      less than 2 cm, no lymphovascular space invasion (LVSI), negative pelvic nodes
      and depth of stromal invasion (DSI) less than 10 mm were identified as the low
      risk group. A total of 243 patients were eligible. Squamous cell carcinomas were
      the most frequent histological cell type (65%). Most patients (81.5%) had tumour
      size less than 2 cm. Thirteen patients (5.3%) had parametrial involvement, 77
      (31.7%) had DSI more than 10 mm, 121 (49.8%) had more than 50% invasion, 119
      (49%) had LVSI and 19 (7.5%) had node metastasis. Ninety-five patients (39.1%)
      were defined as low risk. None of low-risk group had parametrial involvement. DSI
      more than 10 mm or more than 50% stromal invasion, presence of LVSI and pelvic
      node metastasis were significant factors associated with parametrial involvement.
      Parametrial involvement in low-risk, early-stage cervical cancer is extremely
      low. Less radical surgery may be an alternative treatment option.

PMID- 27704643
TI  - Fragmentation pathways and structural characterization of organophosphorus
      compounds related to the Chemical Weapons Convention by electron ionization and
      electrospray ionization tandem mass spectrometry.
AB  - RATIONALE: For unambiguous identification of Chemical Weapons Convention (CWC)
      related chemicals in environmental samples, the availability of mass spectra,
      interpretation skills and rapid microsynthesis of suspected chemicals are
      essential requirements. For the first time, the electron ionization single
      quadrupole and electrospray ionization tandem mass spectra of a series of O-alkyl
      N-[bis(dimethylamino)methylidene]-P-methylphosphonamidates (Scheme 1, cpd 4) were
      studied for CWC verification purposes. METHODS: O-Alkyl N
      [bis(dimethylamino)methylidene]-P-methylphosphonamidates were prepared through a
      microsynthetic method and were analyzed using electron ionization and
      electrospray ionization mass spectrometry with gas and liquid chromatography,
      respectively, as MS-inlet systems. General EI and ESI fragmentation pathways were
      proposed and discussed, and collision-induced dissociation studies of the
      protonated derivatives of these compounds were performed to confirm proposed
      fragment ion structures by analyzing mass spectra of deuterated analogs. RESULTS:
      Mass spectrometric studies revealed some interesting fragmentation pathways
      during the ionization process, such as McLafferty rearrangement, hydrogen
      rearrangement and a previously unknown intramolecular electrophilic aromatic
      substitution reaction. CONCLUSIONS: The EI and ESI fragmentation routes of the
      synthesized compounds 4 were investigated with the aim of detecting and
      identifying CWC-related chemicals during on-site inspection and/or off-site
      analysis and toxic chemical destruction monitoring. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27704644
TI  - Mobility and muscle strength in male former elite endurance and power athletes
      aged 66-91 years.
AB  - The aim of this cross-sectional study was to compare mobility and muscle strength
      in male former elite endurance and power athletes aged 66-91 years (n = 150; 50
      men in both former elite athlete groups and in their control group). Agility,
      dynamic balance, walking speed, chair stand, self-rated balance confidence (ABC
      scale), jumping height, and handgrip strength were assessed. Former elite power
      athletes had better agility performance time than the controls (age- and body
      mass index, BMI-adjusted mean difference -3.6 s; 95% CI -6.3, -0.8). Adjustment
      for current leisure time physical activity (LTPA) and prevalence of diseases made
      this difference non-significant (P = 0.214). The subjects in the power sports
      group jumped higher than the men in the control group (age- and BMI-adjusted mean
      differences for vertical squat jump, VSJ 4.4 cm; 95% CI 2.0, 6.8; for
      countermovement jump, CMJ 4.0 cm; 95% CI 1.7, 6.4). Taking current LTPA and
      chronic diseases for adjusting process did not improve explorative power of the
      model. No significant differences between the groups were found in the
      performances evaluating dynamic balance, walking speed, chair stand, ABC-scale,
      or handgrip strength. In conclusion, power athletes among the aged former elite
      sportsmen had greater explosive force production in their lower extremities than
      the men in the control group.

PMID- 27704645
TI  - Investigation of the anticoagulant and antithrombotic effects of chlorogenic
      acid.
AB  - Thrombosis is a leading cause of morbidity and mortality throughout the world.
      Thrombolytic agents are important for both the prevention and treatment of
      thrombosis. Fibrin clot and turbidity assays revealed that it was able to inhibit
      the formation of fibrin clot. Chlorogenic acid degraded blood clot and inhibited
      the enzymatic activity of procoagulant proteases, thrombin, activated factor X
      (FXa), and activated factor XIII (FXIIIa). Chlorogenic acid was found to delay
      activated partial thromboplastin time, prothrombin time, and thrombin time. PFA
      100 assays showed that it prolonged the closure time of citrated whole human
      blood. It demonstrated the antithrombotic effect in collagen and epinephrine
      induced acute thromboembolism mice model. These antithrombotic profiles together
      with its anticoagulant and platelet disaggregation properties, and lack of
      toxicity to NIH-3T3 and 3T3-L1 cells, make it a potential agent for thrombotic
      treatment and prevention.

PMID- 27704646
TI  - Acquired autoimmune thrombotic thrombocytopenic purpura in a case of severe
      haemophilia A.

PMID- 27704647
TI  - An investigation of the emotion of disgust as an affective barrier to intention
      to screen for colorectal cancer.
AB  - Colorectal cancer (CRC) screening participation remains unacceptably low. This
      study investigated the emotion of disgust as a potential deterrent to intention
      to screen for CRC. The study utilised a convenience sample of individuals' 40-70
      years of age to complete an online survey. Participants included 30 men and 118
      women recruited between December 1, 2013 and March 31, 2014. Data on socio
      demographics, health status, screening intentions and emotional barriers to bowel
      screening were collected via an on-line survey. Logistic regression analysis was
      utilised to investigate predictors of screening intention. Individuals were more
      likely to report intention to screen if they had prior screening experience, and
      reported fewer emotional concerns to screening for CRC. Results implicate disgust
      as a predictor of screening avoidance among participants. Specifically, higher
      reported faecal disgust was predictive of a 3% decrease in screening intention.
      This study was the first to empirically position disgust alongside other negative
      emotional states as an affective barrier to screening for CRC. Trait disgust
      sensitivity was not a reliable predictor of screening intention. This research
      suggests that anticipated faecal disgust may contribute to avoidance of screening
      for CRC.

PMID- 27704648
TI  - A prospective study of von Willebrand factor levels and bleeding in pregnant
      women with type 1 von Willebrand disease.

PMID- 27704649
TI  - Predicting lymph node metastasis in patients with papillary thyroid carcinoma by
      vascular index on power Doppler ultrasound.
AB  - BACKGROUND: For patients with papillary thyroid carcinoma (PTC), lymph node
      metastasis is associated with an increased recurrence rate. The purpose of this
      study was to investigate whether the vascular endothelial growth factor (VEGF),
      microvessel density (MVD), and vascular index (VI) can predict lymph node
      metastasis in patients with PTC. METHODS: From January 2011 to October 2011, 202
      patients with PTCs underwent preoperative staging ultrasound evaluation. To
      evaluate vascularity, we measured the VI, VEGF expression, and MVD. RESULTS: The
      VI was significantly correlated with MVD (p = .009). On multivariate analysis,
      young age showed a significant correlation with lymph node metastasis (p < .001;
      p < .001; p < .001). However, the other clinicopathologic features, VEGF, MVD,
      and VI failed to show any significant correlations with lymph node metastasis.
      CONCLUSION: Although the VI showed significant correlation with MVD, it was not
      significantly correlated to lymph node metastasis. (c) 2016 Wiley Periodicals,
      Inc. Head Neck 39: 334-340, 2017.

PMID- 27704650
TI  - Core-needle biopsy versus repeat fine-needle aspiration for thyroid nodules
      initially read as atypia/follicular lesion of undetermined significance.
AB  - BACKGROUND: The purpose of this study was to evaluate the role of core-needle
      biopsy (CNB) by comparing the results of CNB and repeat fine-needle aspiration
      (FNA) for thyroid nodules that are initially read as atypia/follicular lesion of
      undetermined significance (AUS/FLUS) on FNA. METHODS: Among 2631 initial AUS/FLUS
      FNA results, 505 consecutive nodules (295 repeat FNAs and 210 CNBs) were
      retrospectively analyzed. The primary outcome was inconclusive (ie, nondiagnostic
      or AUS/FLUS). The secondary outcomes included inconclusive results of the
      subcategory, risk factors for inconclusive results, and diagnostic performance.
      RESULTS: CNB demonstrated significantly fewer inconclusive results than repeat
      FNA for the overall nodules (40.9% vs 63%; p < .001). Repeat FNA and group FLUS
      were significant risk factors for inconclusive results (odds ratio = 1.92; p
      =.001 and odds ratio = 2.08; p <.001, respectively). All diagnostic performances
      using CNB were higher than repeat FNAs. CONCLUSION: CNB is more useful than
      repeat FNAs for reducing inconclusive results and improving the diagnostic
      performance of thyroid nodules with initial AUS/FLUS FNA results. (c) 2016 Wiley
      Periodicals, Inc. Head Neck 39: 361-369, 2017.

PMID- 27704651
TI  - Supratracheal partial laryngectomy with tracheohyoidoepiglottopexy (open partial
      horizontal laryngectomy type IIIa + cricoarytenoid unit): Surgical technique
      illustrated in the anatomy laboratory.
AB  - The first supratracheal partial laryngectomy (STPL) with
      tracheohyoidoepiglottopexy was performed in 1972. This procedure entailed
      preservation of the suprahyoid epiglottis as well as a pexy of the hyoid bone and
      residual epiglottis to the first tracheal ring; however, this technique was
      abandoned by the same author in the early 1980s because of poor functional
      outcomes. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 392-398, 2017.

PMID- 27704652
TI  - Epidemiology, clinical characteristics, laboratory findings and severity of
      respiratory syncytial virus acute lower respiratory infection in Malaysian
      children, 2008-2013.
AB  - AIM: The aim of this study is to describe epidemiology, clinical features,
      laboratory data and severity of respiratory syncytial virus (RSV) acute lower
      respiratory infection (ALRI) in Malaysian children and to determine risk factors
      associated with prolonged hospital stay, paediatric intensive care unit (PICU)
      admission and mortality. METHODS: Retrospective data on demographics, clinical
      presentation, outcomes and laboratory findings of 450 children admitted into
      Tuanku Jaafar Hospital in Seremban, Malaysia from 2008 to 2013 with documented
      diagnosis of RSV ALRI were collected and analysed. RESULTS: Most admissions were
      children below 2 years old (85.8%; 386/450). Commonest symptoms were fever
      (84.2%; 379/450), cough (97.8%; 440/450) and rhinorrhea (83.6%; 376/450). The
      median age among febrile patients (n = 379) was 9.0 months with interquartile
      range (IQR) of 4.0-19.0 months whereas the median age among those who were
      apyrexial (n = 71) was 2 months with IQR of 1-6 months (P-value <0.001). 15.3%
      (69/450) needed intensive care and 1.6% (7/450) died. Young age, history of
      prematurity, chronic comorbidity and thrombocytosis were significantly associated
      with prolonged hospital stay, PICU admission and mortality. CONCLUSIONS: Infants
      less than 6 months old with RSV ALRI tend to be afebrile at presentation. Younger
      age, history of prematurity, chronic comorbidity and thrombocytosis are
      predictors of severe RSV ALRI among Malaysian children. Case fatality rate for
      Malaysian children below 5 years of age with RSV ALRI in our centre is higher
      than what is seen in developed countries, suggesting that there is room for
      improvement.

PMID- 27704653
TI  - High-dose intravenous steroid regimen for radiation-induced hypoglossal nerve
      palsy.
AB  - BACKGROUND: Hypoglossal nerve palsies are infrequent complications of head and
      neck radiotherapy. Treatments focus on maintaining function and prevention of
      abnormal airway-related swallowing events. METHODS: A patient with longstanding
      cranial neuropathies, including bilateral hypoglossal involvement, secondary to
      chemoradiotherapy for nasopharyngeal carcinoma, experienced repeated episodes of
      life-threatening complications. Initially, 2 courses of 2 weekly 24-hour
      intravenous methylprednisolone (IVMP) infusions were administered 2 years apart.
      We report the results of a third course comprising 5 weekly cycles. RESULTS:
      Patient-reported outcomes revealed significant improvement in swallowing
      function, speech, and psychosocial status. Airway invasion during swallowing and
      pharyngeal retention were assessed videofluoroscopically and evaluated using the
      Penetration-Aspiration Scale (PAS) and a residue rating scale, respectively. PAS
      ratings after infusions 2 and 5, improved dramatically from baseline and were
      maintained at 1-year follow-up. CONCLUSION: High doses of IVMP may improve
      radiation-induced neuropathies. Further testing in similar patients is needed to
      prove reproducibility. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: E23-E28,
      2017.

PMID- 27704655
TI  - Lower doses of recombinant porcine factor VIII maintain excellent haemostatic
      efficacy.

PMID- 27704654
TI  - The Influence of Skin Redness on Blinding in Transcranial Direct Current
      Stimulation Studies: A Crossover Trial.
AB  - OBJECTIVE: To evaluate whether and to which extent skin redness (erythema)
      affects investigator blinding in transcranial direct current stimulation (tDCS)
      trials. MATERIAL AND METHODS: Twenty-six volunteers received sham and active
      tDCS, which was applied with saline-soaked sponges of different thicknesses. High
      resolution skin images, taken before and 5, 15, and 30 min after stimulation,
      were randomized and presented to experienced raters who evaluated erythema
      intensity and judged on the likelihood of stimulation condition (sham vs.
      active). In addition, semi-automated image processing generated probability
      heatmaps and surface area coverage of erythema. Adverse events were also
      collected. RESULTS: Erythema was present, but less intense in sham compared to
      active groups. Erythema intensity was inversely and directly associated to
      correct sham and active stimulation group allocation, respectively. Our image
      analyses found that erythema also occurs after sham and its distribution is
      homogenous below electrodes. Tingling frequency was higher using thin compared to
      thick sponges, whereas erythema was more intense under thick sponges.
      CONCLUSIONS: Optimal investigator blinding is achieved when erythema after tDCS
      is mild. Erythema distribution under the electrode is patchy, occurs after sham
      tDCS and varies according to sponge thickness. We discuss methods to address skin
      erythema-related tDCS unblinding.

PMID- 27704656
TI  - Long-term liver-related morbidity and mortality related to chronic hepatitis C
      virus infection in Swedish patients with inherited bleeding disorders.
AB  - INTRODUCTION: Hepatitis C virus (HCV) infection is common in patients with
      inherited bleeding disorders treated with clotting factor concentrates prior to
      the introduction of viral inactivation of these products. The long-term
      consequences of hepatitis C infection in Swedish patients are not fully
      understood. AIM: To examine the impact of HCV infection on liver-related
      morbidity and mortality in Swedish patients with inherited bleeding disorders.
      METHODS: We retrospectively collected data on 183 patients with inherited
      bleeding disorders infected with HCV who attended the Coagulation Unit at
      Karolinska University Hospital, Sweden. Data regarding end-stage liver disease
      (ESLD), defined as presence of ascites, encephalopathy, variceal bleeding,
      hepatocellular carcinoma or liver-related death, were collected from the patient
      records and the national registers. RESULTS: The median follow-up time was 35.9
      years (IQR 29.0-41.2). A total of 41% had achieved sustained virological response
      (SVR) after treatment. In total, 14.2% developed ESLD at the median age of 52.6
      years (IQR 46.5-64.7). Nineteen (35.8%) of all deaths were due to liver-related
      causes. Co-infection with human immunodeficiency virus (HIV), older age at time
      of infection and severe form of bleeding disorder was associated with higher risk
      of developing ESLD, while SVR was a strong protective factor. CONCLUSIONS: This
      study demonstrated that liver-related morbidity and mortality was significant in
      patients with bleeding disorders and HCV infection in Sweden. Patients with HCV
      infection should be candidates for treatment with the new highly effective
      antiviral drugs, since SVR proved to be a strong protective factor.

PMID- 27704658
TI  - Moderate X-chromosome inactivation skewing underlies factor VIII activity in
      symptomatic carriers from a family with mild haemophilia A.

PMID- 27704657
TI  - Spontaneous haemoperitoneum in pregnancy and endometriosis: a case series.
AB  - OBJECTIVE: To report pregnancy outcomes of SHiP (spontaneous haemoperitoneum in
      pregnancy) and the association with endometriosis. DESIGN: Retrospective case
      note review. SETTING: Dutch referral hospitals for endometriosis. SAMPLE: Eleven
      women presenting with 15 events of SHiP. METHODS: In collaboration with the Dutch
      Working Group on Endometriosis, unpublished cases of SHiP that occurred in the
      Netherlands between 2010 and 2015 were retrieved. MAIN OUTCOME MEASURES: Maternal
      and perinatal mortality and morbidity. RESULTS: SHiP occurred predominantly in
      the second and third trimester of pregnancy. The earliest and major presenting
      symptom was an acute onset of abdominal pain, often combined with low haemoglobin
      levels or signs of fetal distress. Imaging was a diagnostic tool when free
      peritoneal fluid could be observed. For surgical treatment of the bleeding site,
      a midline laparotomy was mostly needed, the median estimated amount of blood loss
      was 2000 mL. No fetomaternal or perinatal mortality was reported, despite a high
      rate of preterm births (54.5%). In all women, endometriosis was diagnosed at a
      certain moment in time and therefore was probably involved in the pathogenesis of
      SHiP. Four women showed recurrence of SHiP. In one of these cases the second
      event of SHiP occurred in a subsequent pregnancy. CONCLUSION: Pregnancy outcomes
      of SHiP are improving when compared with previous reports, with absent
      fetomaternal and perinatal mortality in this recent series. Growing knowledge and
      adequate multidisciplinary intervention may have contributed to these favourable
      results. Increasing awareness of this serious complication of pregnancy is
      advocated, especially in women diagnosed with endometriosis. TWEETABLE ABSTRACT:
      Growing awareness of SHiP is advocated, especially in women diagnosed with
      endometriosis.

PMID- 27704659
TI  - An assessment of the relationship between the World Health Organization HIV drug
      resistance early warning indicators and HIV drug resistance acquisition.
AB  - OBJECTIVES: The World Health Organization (WHO)'s HIV drug resistance (HIVDR)
      early warning indicators (EWIs) measure antiretroviral therapy (ART)-site factors
      associated with HIVDR prevention, without HIVDR laboratory testing. We assessed
      the relationship between EWIs and HIVDR acquisition using data from British
      Columbia, Canada. METHODS: Eligible patients were ART-naive, were >= 19 years
      old, had initiated ART between 1 January 2000 and 31 December 2012, had >= 15
      months of follow-up, and were without transmitted HIVDR. Patients were followed
      for acquired HIVDR until 31 March 2014, the last contact date, or death. We built
      logistic regression models to assess the associations and predictive ability of
      individual indicators and of the EWI Score (the number of indicators for which a
      patient did not meet the criteria) on HIVDR acquisition (to any class of HIVDR,
      lamivudine (3TC)/emtricitabine (FTC), nonnucleoside reverse transcriptase
      inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) or
      protease inhibitors (PIs)]). RESULTS: All explored EWIs were associated with at
      least one class of HIVDR, with the exception of 'ART prescribing practices'. We
      observed a dose-response relationship between acquiring HIVDR to any
      antiretroviral class and an increasing EWI score in our predictive logistic
      regression model. The area under the curve was 0.848 (excellent discrimination).
      The adjusted odds ratios for acquiring any class of HIVDR for an EWI score of 1,
      2 and >= 3 versus 0 were 2.30 [95% confidence Interval (CI) 1.21-4.38], 3.35 (95%
      CI: 1.86-6.03) and 7.26 (95% CI: 4.18-12.61), respectively. CONCLUSIONS: Several
      EWIs were associated with and predictive of HIVDR, supporting the WHO EWIs as a
      component of the HIVDR prevention method in settings where HIVDR testing is not
      routinely or widely available.

PMID- 27704660
TI  - Efficacy of ultrasound-guided fine-needle aspiration performed by surgeons newly
      trained in thyroid ultrasound.
AB  - BACKGROUND: There are a growing number of thyroid ultrasound courses to train
      endocrinologists, pathologists, and surgeons to perform ultrasound-guided fine
      needle aspiration (FNA). However, there are limited data to support the efficacy
      of ultrasound-guided FNA performed by nonradiologists. METHODS: We compared the
      efficacy of ultrasound-guided FNA performed by surgeons newly trained in thyroid
      ultrasound with that of the same technique performed by 1 experienced
      radiologist. The ratio of nondiagnostic examinations was used to compare the 2
      groups. RESULTS: A total of 197 ultrasound-guided FNAs were performed on 172
      women (95.53%) and 8 men (4.47%) over a 12-month period. The efficacy of
      ultrasound-guided FNA did not differ between groups. A nondiagnostic report was
      found in 23% and 25.7% of the examinations performed by the radiologist and
      surgeons, respectively. CONCLUSION: The efficacy of ultrasound-guided FNAs
      performed by our 2 surgeons was similar to that of our radiologist. (c) 2016
      Wiley Periodicals, Inc. Head Neck 39: 439-442, 2017.

PMID- 27704662
TI  - Cigarette smoking alters sialylation in the Fallopian tube of women, with
      implications for the pathogenesis of ectopic pregnancy.
AB  - Sialylation creates a negative charge on the cell surface that can interfere with
      blastocyst implantation. For example, alpha2,6-sialylation on terminal galactose,
      catalyzed by the sialyltransferase ST6GAL1, inhibits the binding of galectin-1, a
      beta-galactoside-binding lectin. We recently reported the potential involvement
      of galectin-1 and -3 in the pathogenesis of tubal ectopic pregnancy; however, the
      precise role of galectins and their ligand glycoconjugates remain unclear. Here,
      we investigated the expression of the genes encoding alpha2,3- and alpha2,6
      galactoside sialyltransferases (ST3GAL1-6 and ST6GAL1-2) and the localization of
      sialic acids in the Fallopian tube of women with or without ectopic implantation.
      ST6GAL1 expression was higher in the mid-secretory phase than the proliferative
      phase of non-pregnant women (P < 0.0001), whereas ST6GAL1 (P < 0.0001), ST3GAL3
      (P = 0.0029), ST3GAL5 (P = 0.0089), and ST3GAL6 (P = 0.0018) were all lower in
      Fallopian tubes with ectopic implantations. alpha2,3- and alpha2,6-sialic acids,
      however, both remained enriched on the surface of Fallopian tube epithelium.
      Cigarette smoking, a major risk factor for tubal ectopic pregnancy, was
      associated with reduced mid-secretory-phase expression of ST6GAL1 (P = 0.0298),
      but elevated expression of ST3GAL5 (P = 0.0006), an enzyme known to be involved
      in ciliogenesis. Indeed, sialic acid-containing ciliated inclusion cysts, which
      are associated with abnormal ciliogenesis, were observed within the epithelium at
      a higher frequency in women who smoked (P = 0.0177), suggesting that abnormal
      ciliogenesis is associated with smoking. Thus, cigarette smoking alters
      sialylation in the Fallopian tube epithelium, and is potentially a source of
      decreased tubal transport and increased receptivity for blastocyst in the human
      Fallopian tube. Mol. Reprod. Dev. 83: 1083-1091, 2016. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27704661
TI  - Isolated local recurrence or solitary solid organ metastasis after esophagectomy
      for cancer is not the end of the road.
AB  - Recurrent disease after esophagectomy bears an infaust prognosis, especially when
      multiple recurrences are present. But little is known about survival in patients
      with limited recurrence (solitary locoregional recurrence or solid organ
      metastasis). Herein, we report our experience with these subgroups. We analyzed
      1754 consecutive patients surgically treated with curative resection for
      esophageal cancer and cancer of the gastroesophageal junction between 1990 and
      2012. Seven subgroups were defined according to the recurrence type (locoregional
      vs. organ metastasis), the site of recurrence (abdominal, thoracic, cervical for
      lymph nodes and lung, liver, adrenals and others for organ metastasis) and also
      the number of lesions (one vs. multiple lymph node stations or organ metastasis)
      Of these groups; clinical isolated locoregional recurrence (ciLR) was defined as
      solitary lymph-node recurrence confined to one compartment (cervical, thoracic or
      abdominal, within or outside surgical dissection-field) at clinical staging.
      Clinical solitary solid organ metastasis (csSOM) was defined as metastasis in a
      resectable solid organ, i.e. liver, lung, brain or adrenal. Salvage therapies
      were grouped in five categories. Kaplan-Meier curves were used to calculate
      survival. Recurrent disease was observed in 766 patients (43.7%) with overall 5
      year survival of 4.5% after diagnosis of recurrence. Fifty-seven patients (7.4%)
      showed ciLR and 110 (14.4%) csSOM. Median time-to-recurrence was 16.8 months in
      ciLR and 9.9 months in csSOM (P = 0.0074). Survival is significantly improved
      compared to supportive therapy when local therapy is possible (P < 0.0001). In 25
      (15%) of ciLR or csSOM patients, surgical therapy with or without systemic
      therapy, yielded a 5-year survival of 49.9% (median 54.8 months) after diagnosis
      of recurrence. When surgery was impossible or contraindicated, the combination of
      chemoradiotherapy appeared to be superior to chemotherapy alone (respectively
      27.0% vs. 4.6% 5-year survival) or radiotherapy alone (no 5-year survival).
      Recurrent disease after esophagectomy is a common problem with poor overall
      survival. However prolonged survival could be obtained in selected patients if
      the recurrent disease is limited to ciLR or csSOM, if surgery (+/- systemic
      therapy) can be performed. If not a combination of chemoradiotherapy seems to
      offer the second best option. Patients presenting with a ciLR or csSOM should be
      discussed in a dedicated multidisciplinary team meeting as to evaluate and define
      the place of salvage treatment which in well selected cases could offer a
      perspective of prolonged survival.

PMID- 27704663
TI  - Parent-Related Stress of Male and Female Carers of Adolescents with Intellectual
      Disabilities and Carers of Children within the General Population: A Cross
      Sectional Comparison.
AB  - BACKGROUND: Carers of children with intellectual disability show high rates of
      parent-related stress and are at an increased risk for deleterious physical and
      mental health. MATERIALS AND METHODS: This study investigated the relationship
      between demographic and social characteristics and parenting stress, within two
      different cross-sectional samples of carers: those who care for an adolescent
      with an intellectual disability and carers from a population based sample.
      Participants were 1152 carers from the Household Income and Labour Dynamic in
      Australia study and 284 carers of adolescents with intellectual disabilities from
      the Ask study. RESULTS AND CONCLUSIONS: The results supported previous research
      suggesting carers of children with intellectual disabilities experience high
      parent-related stress. The results also support the buffer model of social
      support, as high social support was related to lower parent-related stress. Self
      rated prosperity, financial pressure and relationship status were also related to
      lower levels of parent-related stress.

PMID- 27704664
TI  - Content analysis of public opinion on sexual expression and dementia:
      Implications for nursing home policy development.
AB  - PURPOSE: We examined public opinion of sexual expression and dementia to inform
      nursing home policy and practice. DESIGN AND METHODS: A content analysis was
      conducted on public comments (N=1194) posted in response to a New York Times
      article about a highly publicized legal case involving a husband engaging in
      sexual acts with his wife who had dementia, living in a nursing home. Researchers
      utilized constant comparative analysis to code the comments; reliability analysis
      showed moderately strong agreement at the subcategory level. Data were also coded
      to indicate whether the commenter thought the couple should or should not have
      been allowed to be sexual. RESULTS: One primary theme was identified: conditions
      necessary for someone to be sexual. Six categories were identified within this
      theme, with the public commentary considering factors such as marital
      relationships, intimacy needs and several sexual consent-related issues as key
      conditions necessary to be sexual in a nursing home setting. Overall, the
      majority of commenters were in support of sexual expression for an individual
      with dementia in the described situation. DISCUSSION: This study revealed sexual
      expression among individuals with dementia is a contentious issue with strong
      public opinions about how this should be managed in a nursing home setting. These
      opinions should be considered as policy related to sexual expression in nursing
      homes is developed.

PMID- 27704665
TI  - Predictive parameter of tolvaptan effectiveness in cirrhotic ascites.
AB  - AIMS: The efficacy of the vasopressin V2 receptor antagonist tolvaptan for
      difficult-to-treat cirrhotic ascites has recently been reported. However, its
      effect is variable among patients. This study aimed to clarify the predictive
      factors for obtaining a good response to tolvaptan in patients with difficult-to
      treat ascites. METHODS: Data were collected from 50 patients with liver cirrhosis
      having ascites (hepatitis B, n = 1; hepatitis C, n = 22; alcoholism, n = 11; and
      others, n = 16) after treatment with tolvaptan (3.75-7.5 mg/day) in addition to
      conventional diuretics. A follow-up assessment was carried out after 7-day
      tolvaptan treatment for all patients. RESULTS: After an uneventful 7-day
      tolvaptan treatment, 18 patients (36.0%) lost more than 2 kg of their body weight
      (responders). Twenty-six patients (52.0%) showed an increase in urine volume
      (>300 mL) on day 2. Tolvaptan was also effective for patients with pleural
      effusion, portal vein thrombosis, and hepatocellular carcinoma. Basal blood urea
      nitrogen (BUN) levels, plasma renin activity, and aldosterone levels were
      significantly higher in the poor responders (<2 kg weight loss), who were
      considered to be in the relative vascular underfilling state, than in the
      responders. Basal BUN was extracted as a predictive factor of responsiveness by
      multivariate logistic regression analysis. CONCLUSIONS: Tolvaptan is useful and
      safe for the treatment of cirrhotic ascites. This report showed that BUN will
      predict the response of tolvaptan even when measured before tolvaptan treatment.

PMID- 27704666
TI  - Versatility of the facial artery myomucosal island flap in neopharyngeal
      reconstruction.
AB  - BACKGROUND: The facial artery myomucosal (FAMM) island flap is a cheek flap,
      pedicled on the facial artery and suitable for small to medium-sized
      reconstructions of the oral cavity and neighboring areas. A novel transposition
      of the flap to the hypopharynx after laryngectomy is presented in this report.
      METHODS: A 58-year-old man, previously irradiated, was laryngopharyngectomized
      because of a new supraglottic carcinoma. An unexpected need for a flap was solved
      by tunneling a FAMM island flap lateral to the mandible. The reach and size of
      the flap were sufficient to close the defect. RESULTS: Vitality of the flap was
      ascertained by fiber endoscopy. No donor-site morbidity was seen.
      Postoperatively, the patient had a minor stomal fistula with spontaneous healing.
      CONCLUSION: The pedicled FAMM island flap may be considered for smaller
      reconstructions of the upper hypopharynx. Accessibility, low donor-site
      morbidity, and recipient tissue similarity count among the advantages. (c) 2016
      Wiley Periodicals, Inc. Head Neck 39: E29-E33, 2017.

PMID- 27704667
TI  - Quality of life following fistulotomy - short term follow-up.
AB  - AIM: Anal fistula causes pain and discharge of pus and blood. Treatment by
      fistulotomy has the highest success, but can risk continence; treatment needs to
      balance cure with continence. This study assessed the impact of fistulotomy on
      quality of life (QOL) and continence. METHOD: Patients selected for fistulotomy
      prospectively completed the St Mark's Continence Score (full incontinence = 24)
      and Short Form-36 questionnaires preoperatively at two institutions with an
      interest in anal fistula. Patients were reassessed 3 months' postoperatively.
      RESULTS: There were 52 patients with a median age of 44 (range 19-82) years; 10
      were women. Preoperative continence scores were median 0 (range 0-23) and there
      was no significant difference compared with postoperative scores (median 1, range
      0-24). Following fistulotomy QOL was significantly improved in four of eight
      domains - Bodily Pain (P < 0.001), Vitality (P < 0.01), Social Functioning (P <
      0.05) and Mental Health (P < 0.001) - and returned to that of the general
      population. QOL for patients with intersphincteric fistula improved
      postfistulotomy, and for those with trans-sphincteric fistula it remained the
      same. Data were further examined in two groups, with and without deterioration in
      continence score. Where continence improved postoperatively, QOL improved in
      three domains; where continence deteriorated QOL improved in two domains (P <
      0.05). Patients with postoperative continence scores of < 5 had worse QOL than
      those scoring 4 or less. CONCLUSION: QOL significantly improved at 3 months'
      follow-up after fistulotomy where continence was maintained or a small reduction
      occurred.

PMID- 27704668
TI  - Re: Prevalence of prenatal brain abnormalities in fetuses with congenital heart
      disease: a systematic review.

PMID- 27704669
TI  - Re: Perinatal outcomes and intrauterine complications following fetal
      intervention for congenital heart disease: systematic review and meta-analysis of
      observational studies. E. Araujo Junior, G. Tonni, M. Chung, R. Ruano and W. P.
      Martins. Ultrasound Obstet Gynecol 2016; 48: 426-433.

PMID- 27704670
TI  - Erratum.

PMID- 27704671
TI  - Reply.

PMID- 27704672
TI  - Can third-trimester assessment of uterine scar in women with prior Cesarean
      section predict uterine rupture?

PMID- 27704673
TI  - Re: Narrow subpubic arch angle is associated with higher risk of persistent
      occiput posterior position at delivery. T. Ghi, A. Youssef, F. Martelli, F.
      Bellussi, E. Aiello, G. Pilu, N. Rizzo, T. Frusca, D. Arduini and G. Rizzo.
      Ultrasound Obstet Gynecol 2016; 48: 511-515.

PMID- 27704674
TI  - Heteroatom-Doped Porous Carbon Nanosheets: General Preparation and Enhanced
      Capacitive Properties.
AB  - High-performance electrical double-layer capacitors (EDLCs) require carbon
      electrode materials with high specific surface area, short ion-diffusion
      pathways, and outstanding electrical conductivity. Herein, a general approach
      combing the molten-salt method and chemical activation to prepare N-doped carbon
      nanosheets with high surface area (654 m2  g-1 ) and adjustable porous structure
      is presented. Owing to their structural features, the N-doped carbon nanosheets
      exhibited superior capacitive performance, demonstrated by a maximum capacitance
      of 243 F g-1 (area-normalized capacitance up to 37 MUF cm-2 ) at a current
      density of 0.5 A g-1 in aqueous electrolyte, high rate capability (179 F g-1 at
      20 A g-1 ), and excellent cycle stability. This method provides a new route to
      prepare porous and heteroatom-doped carbon nanosheets for high-performance EDLCs,
      which could also be extended to other polymer precursors and even waste biomass.

PMID- 27704676
TI  - The Editor recommends this issue's article to the reader: Hypophosphatasia:
      diagnosis and clinical signs - a dental surgeon perspective.

PMID- 27704675
TI  - Factors associated with psychotic relapse in patients with schizophrenia in a
      Pakistani cohort.
AB  - Despite a large body of research evaluating factors associated with the relapse
      of psychosis in schizophrenia, no studies in Pakistan have been undertaken to
      date to identify any such factors, including specific cultural factors pertinent
      to Pakistan. Semistructured interviews and psychometric measures were undertaken
      with 60 patients diagnosed with schizophrenia (49 male and 11 female) and their
      caregivers at four psychiatric hospitals in the Peshawar region in Pakistan.
      Factors significantly associated with psychotic relapse included treatment non
      adherence, comorbid active psychiatric illnesses, poor social support, and high
      expressed emotion in living environments (P < 0.05). The attribution of symptoms
      to social and cultural values (97%) and a poor knowledge of psychosis by family
      members (88%) was also prevalent. In addition to many well-documented factors
      associated with psychotic relapse, beliefs in social and cultural myths and
      values were found to be an important, and perhaps treatable, factor associated
      with relapse of psychosis in Pakistan. The provision of evidence-based
      psychotherapeutic interventions, such as behaviour and family therapy and
      cognitive behaviour therapy for psychosis, could potentially ameliorate the
      relapse rate of psychosis in Pakistan.

PMID- 27704677
TI  - Clinical interventions to reduce stillbirths in sub-Saharan Africa: a
      mathematical model to estimate the potential reduction of stillbirths associated
      with specific obstetric conditions.
AB  - OBJECTIVE: Stillbirths are among the most common adverse pregnancy outcomes, with
      98% occurring in low-income countries. More than one-third occur in sub-Saharan
      Africa (SSA). However, the medical conditions causing stillbirths and
      interventions to reduce stillbirths from these conditions are not well
      documented. We estimated the reductions in stillbirths possible with combinations
      of interventions. DESIGN: We developed a computerised model to estimate the
      impact of various interventions on stillbirths caused by the most common
      conditions. The model considered the location of obstetric care (home, clinic or
      hospital) and each intervention's efficacy, penetration and utilisation. Maternal
      transfers were also considered. SETTING AND POPULATION: Pregnancies in SSA in
      2012. METHODS: For each condition, we created a series of scenarios involving
      different combinations of interventions and modelled their impact on stillbirth
      rates. MAIN OUTCOME MEASURES: Stillbirths associated with various maternal and
      fetal conditions and the percentage reduction with various interventions.
      RESULTS: Eight to ten maternal and fetal conditions were responsible for most
      stillbirths, but none for more than 15%. The most common conditions causing
      stillbirths in SSA include obstructed labour and uterine rupture, fetal distress
      and umbilical cord complications, fetal growth restriction, pre
      eclampsia/eclampsia, and placental abruption/placenta praevia. Syphilis and
      malaria contribute smaller numbers. Reducing stillbirths requires appropriate
      diagnosis and management of each condition, usually including hospital care for
      monitoring and delivery, often by caesarean section. Maternal syphilis and
      malaria were the only conditions for which outpatient management alone reduced
      stillbirth. CONCLUSIONS: Most stillbirths in low-income countries occur at term
      and during labour and therefore are preventable by appropriate obstetric care.
      Management focused on the maternal and fetal conditions that cause stillbirths is
      necessary to achieve stillbirth rates approaching those found in high-income
      countries. TWEETABLE ABSTRACT: Reducing stillbirth incidence requires appropriate
      management of each causative condition and often caesarean delivery.

PMID- 27704678
TI  - The Accuracy of Anthropometric Equations to Assess Body Fat in Adults with Down
      Syndrome.
AB  - BACKGROUND: The aim of this study was to verify the accuracy of anthropometric
      equations to estimate the body density (BD) of adults with Down syndrome (DS),
      and propose new regression equations. MATERIALS AND METHODS: Twenty-one males
      (30.5 +/- 9.4 years) and 17 females (27.3 +/- 7.7 years) with DS participated in
      this study. The reference method for BD was air displacement plethysmography
      (ADP). Also, the BD was estimated by anthropometric equations. The body fat
      percentage (BF %) was estimated by the Siri equation. RESULTS: For females, the
      Durnin and Womersley equation showed no difference from the ADP, but a trend of
      underestimation was observed. For males, all equations were significantly
      different for the BF % from ADP. The equations developed in this study showed a
      high correlation and acceptable agreement with BF % from ADP in both genders.
      CONCLUSION: All equations are not valid for DS adults. The new equations
      developed here were accurate in estimating the BF %.

PMID- 27704679
TI  - Vitamin D, pre-eclampsia, and preterm birth among pregnancies at high risk for
      pre-eclampsia: an analysis of data from a low-dose aspirin trial.
AB  - OBJECTIVE: To examine the relation between maternal vitamin D status and risk of
      pre-eclampsia and preterm birth in women at high risk for pre-eclampsia. DESIGN:
      Analysis of prospectively collected data and blood samples from a trial of
      prenatal low-dose aspirin. SETTING: Thirteen sites across the USA. POPULATION:
      Women at high risk for pre-eclampsia. METHODS: We measured 25-hydroxyvitamin D
      [25(OH)D] concentrations in stored maternal serum samples drawn at 12-26 weeks'
      gestation (n = 822). We used mixed effects models to examine the association
      between 25(OH)D and risk of pre-eclampsia and preterm birth, controlling for
      confounders including prepregnancy BMI and race. MAIN OUTCOME MEASURES: Pre
      eclampsia and preterm birth. RESULTS: Twelve percent of women were vitamin D
      deficient [25(OH)D <30 nmol/l]. Women with 25(OH)D <30 versus >=75 nmol/l had a
      2.4-fold (95% CI 1.0-5.6) higher risk of early-onset pre-eclampsia (<35 weeks'
      gestation) after confounder adjustment. Women with 25(OH)D <50 nmol/l had a 1.8
      fold (95% CI 1.0-3.2) increased risk of preterm birth at <35 weeks compared with
      women who had 25(OH)D >=75 nmol/l, which was driven by indicated preterm births
      at <35 weeks' gestation [25(OH)D <50 versus >=75 nmol/l adjusted RR 2.5 (95% CI
      1.1-5.8)]. There was no association between vitamin D status and pre-eclampsia or
      preterm birth at <37 weeks. CONCLUSION: Maternal vitamin D status in the second
      trimester was inversely associated with risk of early-onset pre-eclampsia and
      preterm birth at <35 weeks in women at high risk for pre-eclampsia. TWEETABLE
      ABSTRACT: Vitamin D is inversely related to risk of pre-eclampsia and preterm
      birth at <35 weeks in high-risk pregnancies.

PMID- 27704680
TI  - Risk stratification using Bmi-1 and Snail expression is a useful prognostic tool
      for patients with upper tract urothelial carcinoma.
AB  - OBJECTIVES: To investigate the expression levels of E-cadherin, Snail, Twist and
      Bmi-1 in the human upper tract urothelial carcinoma, and to assess whether these
      factors could be prognostic markers. METHODS: Immunohistochemistry was carried
      out to determine the expression of E-cadherin, Snail, Twist and Bmi-1 in upper
      tract urothelial carcinoma samples from 144 patients that underwent total
      nephroureterectomy between January 1995 and December 2010. The patient population
      had a median age of 71 years, and comprised 104 men and 40 women, with a median
      follow-up period of 40 months. The prognostic value of these markers was assessed
      by univariate and multivariate analysis. A risk stratification analysis was
      carried out. RESULTS: Snail and Bmi-1 expression predicted worse overall survival
      (P = 0.0075 and 0.0035), cancer-specific survival (P = 0.0919 and 0.0085) and
      recurrence-free survival (P = 0.0360 and 0.0817, respectively) compared with
      tumors that lacked Snail and Bmi-1 expression. Additionally, clinical parameters,
      grade, stage and lymphovascular invasion correlated with overall survival, cancer
      specific survival and recurrence-free survival. Multivariate analysis showed that
      Bmi-1 expression was among the most significant factors in predicting cancer
      specific survival (P = 0.0333). The combination of Snail, Bmi-1 and pathological
      stage was the most useful prognostic biomarker for upper tract urothelial
      carcinoma. CONCLUSION: Risk stratification by epithelial-mesenchymal transition
      and cancer stem cell-regulated genes, such as Snail and Bmi-1, might be useful
      prognostic markers for upper tract urothelial carcinoma.

PMID- 27704681
TI  - Tyrosine peptides provide a color palette upon tyrosinase oxidation: nanosize
      does matter.

PMID- 27704682
TI  - The clinical value of the controlled attenuation parameter in the follow-up of
      HIV-infected patients.

PMID- 27704683
TI  - The Comparison of Porous Titanium Granule and Xenograft in the Surgical Treatment
      of Peri-Implantitis: A Prospective Clinical Study.
AB  - BACKGROUND: Regarding the current approach, there is no evidence to show which
      treatment technique is the most accurate and useful in peri-implant defects.
      PURPOSE: The aim of this study is comparing the effect of porous titanium granule
      (PTG) with rotary titanium brush and the use of xenograft and collagen membrane
      in the treatment of intra-bony peri-implant defects. MATERIALS AND METHODS:
      Twenty-two patients, suffering peri-implantitis defects were included this study.
      Patients were divided into two groups: The PTG group used rotary titanium brush,
      PTG, and platelet rich fibrin (PRF) membrane. The XGF group used xenograft bone
      substitute, collagen membrane, and PRF membrane. Clinical measurements and cone
      beam computed tomography per region were recorded as baseline and sixth month
      after surgery. RESULTS: The mean CAL values were improved from 5.29 +/- 1.06 to
      3.59 +/- 0.88 mm in PTG group, while in XGF group; these values were improved
      from 4.77 +/- 1.05 to 3.30 +/- 0.58 mm. Radiographic bone filling values
      displayed a statistically significant difference between of groups. In PTG
      groups, these radiological values increased more than the XGF group. CONCLUSIONS:
      PTG may be more appropriate for peri-implantitis surgery than xenograft due to
      inert structure and comfortable use of PTG to provide mechanical support for
      enlarging the surface area of the implant.

PMID- 27704685
TI  - Singular Novel Technology With Varied Techniques For Implementation.

PMID- 27704686
TI  - Tackling inequalities in cancer care and outcomes: psychosocial mechanisms and
      targets for change.

PMID- 27704684
TI  - CJCheck Stage 1: development and testing of a checklist for reporting community
      juries - Delphi process and analysis of studies published in 1996-2015.
AB  - BACKGROUND: Opportunities for community members to actively participate in policy
      development are increasing. Community/citizen's juries (CJs) are a deliberative
      democratic process aimed to illicit informed community perspectives on difficult
      topics. But how comprehensive these processes are reported in peer-reviewed
      literature is unknown. Adequate reporting of methodology enables others to judge
      process quality, compare outcomes, facilitate critical reflection and potentially
      repeat a process. We aimed to identify important elements for reporting CJs, to
      develop an initial checklist and to review published health and health policy CJs
      to examine reporting standards. DESIGN: Using the literature and expertise from
      CJ researchers and policy advisors, a list of important CJ reporting items was
      suggested and further refined. We then reviewed published CJs within the health
      literature and used the checklist to assess the comprehensiveness of reporting.
      RESULTS: CJCheck was developed and examined reporting of CJ planning, juror
      information, procedures and scheduling. We screened 1711 studies and extracted
      data from 38. No studies fully reported the checklist items. The item most
      consistently reported was juror numbers (92%, 35/38), while least reported was
      the availability of expert presentations (5%, 2/38). Recruitment strategies were
      described in 66% of studies (25/38); however, the frequency and timing of
      deliberations was inadequately described (29%, 11/38). CONCLUSIONS: Currently CJ
      publications in health and health policy literature are inadequately reported,
      hampering their use in policy making. We propose broadening the CJCheck by
      creating a reporting standards template in collaboration with international CJ
      researchers, policy advisors and consumer representatives to ensure standardized,
      systematic and transparent reporting.

PMID- 27704687
TI  - Diprosopus: Systematic review and report of two cases.
AB  - BACKGROUND: Diprosopus is a subtype of symmetric conjoined twins with one head,
      facial duplication and a single trunk. Diprosopus is a very rare congenital
      anomaly. METHODS: This is a systematic review of published cases and the
      presentation of two new cases born in Argentina. We estimated the prevalence of
      conjoined twins and diprosopus using data from the National Network of Congenital
      Anomalies of Argentina (RENAC). RESULTS: The prevalence of conjoined twins in
      RENAC was 19 per 1,000,000 births (95% confidence interval, 12-29). Diprosopus
      prevalence was 2 per 1,000,000 births (95% confidence interval, 0.2-6.8). In the
      systematic review, we identified 31 diprosopus cases. The facial structures more
      frequently duplicated were nose and eyes. Most frequent associated anomalies
      were: anencephaly, duplication of cerebral hemispheres, craniorachischisis, oral
      clefts, spinal abnormalities, congenital heart defects, diaphragmatic hernia,
      thoracic and/or abdominal visceral laterality anomalies. One of the RENAC cases
      and three cases from the literature had another discordant nonmalformed twin.
      CONCLUSION: The conjoined twins prevalence was similar to other studies. The
      prevalence of diprosopus was higher. The etiology is still unknown. The presence
      of visceral laterality anomalies may indicate the link between diprosopus and the
      alteration or duplication of the primitive node in the perigastrulation period
      (12-15 days postfertilization). Pregnancies of more than two embryos may be a
      risk factor for diprosopus. Given the low prevalence of this defect, it would be
      useful to perform studies involving several surveillance systems and
      international consortiums. Birth Defects Research (Part A), 2016. (c) 2016 Wiley
      Periodicals, Inc. Birth Defects Research (Part A) 106:993-1007, 2016. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27704692
TI  - Response: High Frequency (10 kHz) or Burst Spinal Cord Stimulation in Failed Back
      Surgery Syndrome Patients With Predominant Back Pain: Preliminary Data From a
      Prospective Observational Study.

PMID- 27704690
TI  - Response: A Systematic Evaluation of Burst Spinal Cord Stimulation for Chronic
      Back and Limb Pain.

PMID- 27704689
TI  - Connective tissue growth factor (CTGF/CCN2) in haemophilic arthropathy and
      arthrofibrosis: a histological analysis.
AB  - INTRODUCTION: Joint haemorrhage is the principal clinical manifestation of
      haemophilia frequently leading to advanced arthropathy and arthrofibrosis,
      resulting in severe disability. The degree and prevalence of arthrofibrosis in
      hemophilic arthropathy is more severe than in other forms of arthropathy.
      Expression of connective tissue growth factor (CTGF) has been linked to many
      fibrotic diseases, but has not been studied in the context of haemophilic
      arthropathy. AIM: We aim to compare synovial tissues histologically from
      haemophilia and osteoarthritis patients with advanced arthropathy in order to
      compare expression of proteins that are possibly aetiologic in the development of
      arthrofibrosis. METHODS: Human synovial tissues were obtained from 10 haemophilia
      and 10 osteoarthritis patients undergoing joint surgery and processed for
      histology and immunohistochemistry. RESULTS: All samples from haemophilia
      patients had synovitis with hypertrophy and hyperplasia of synovial villi.
      Histologically, synovial tissues contained hyperplastic villi with increased
      cellularity and abundant haemosiderin- and ferritin-pigmented macrophage-like
      cells (HMCs), with a perivascular localization in the sub-surface layer. CTGF
      staining was observed in the surface layer and sub-surface layer in all
      haemophilia patients, exclusively co-localizing with HMCs. Quantification showed
      that the extent of CTGF-positive areas was correlated with the degree of
      detection of HMCs. CTGF was not observed in any of the samples from
      osteoarthritis patients. CONCLUSION: Using histological analysis, we showed that
      CTGF expression is elevated in haemophilia patients with arthrofibrosis and
      absent in patients with osteoarthritis. Additionally, we found that CTGF is
      always associated with haemosiderin-pigmented macrophage-like cells, which
      suggests that CTGF is produced by synovial A cells following the uptake of blood
      breakdown products.

PMID- 27704688
TI  - FAK contributes to proteinuria in hypercholesterolaemic rats and modulates
      podocyte F-actin re-organization via activating p38 in response to ox-LDL.
AB  - Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that
      regulates cell adhesion, proliferation and differentiation. In the present study,
      a rat model of high fat diet-induced hypercholesterolaemia was established to
      investigate the involvement of FAK in lipid disorder-related kidney diseases. We
      showed focal fusion of podocyte foot process that occurred at as early as 4 weeks
      in rats consuming high fat diet, preceding the onset of proteinuria when aberrant
      phosphorylation of FAK was found. These abnormalities were ameliorated by dietary
      intervention of TAE226, a reported inhibitor of FAK. FAK is also an adaptor
      protein initiating cascades of intracellular signals including c-Src, Rho GTPase
      and mitogen-activated protein kinase (MAPK). P38 MAPK belongs to the latter and
      is centrally involved in kidney diseases. Our cell culture data revealed oxidized
      low-density lipoprotein (ox-LDL) triggered hyper-phosphorylation of FAK and p38,
      ectopic expression of cellular markers (manifested as decreased WT1, podocin and
      NEPH1, and increased vimentin and mmp9), and re-arrangement of F-actin filaments
      with enhanced cell motility; these mutations were significantly rectified by FAK
      shRNA. Notably, pre-treatment of p38 inhibitor did not alter FAK activation,
      albeit its deletion of p38 hyper-activity and attenuation of cellular
      abnormalities, demonstrating that p38 acted as a downstream effector of FAK
      signalling and ox-LDL damaged podocytes in a FAK/p38-dependent manner. This was
      further identified by animal data that p38 activation was also abrogated by
      TAE226 treatment in hypercholesterolaemic rats, suggesting that FAK/p38 axis
      might also be involved in in vivo events. These findings provided a potential
      early mechanism of hypercholesterolaemia-related podocyte damage and proteinuria.

PMID- 27704693
TI  - Structural Analysis and Application of n-Alkyl Cyanoacrylate Surgical Adhesives
      to the Fixation of Meshes for Hernia Repair.
AB  - The article deals with a comparative analysis of the parameters of the
      polymerization in physiological conditions of three commercially available alkyl
      cyanoacrylates, n-butyl cyanoacrylate (GLUBRAN 2), n-hexyl cyanoacrylate
      (IFABOND), and n-octyl cyanoacrylate (EVOBOND), the cell behavior of the
      corresponding polymers and the application of these adhesives in the fixation of
      surgical polypropylene meshes for hernia repair in an animal model of rabbits.
      The results obtained demonstrate that the curing process depends on the nature of
      the alkyl residue of the ester group of cyanoacrylate molecules, being the heat
      of polymerization lower for the octyl derivative in comparison with the hexyl and
      butyl, and reaching a maximum temperature of 35  degrees C after a time of mixing
      with physiological fluids of 60-70 s. The cell behavior demonstrates that the
      three systems do not present toxicity for fibroblasts and low adhesion of cells,
      which is a positive result for application as tissue adhesives, especially for
      the fixation of abdominal polypropylene meshes for hernia repair. The animal
      experimentation indicates the excellent tolerance of the meshes fixed with the
      cyanoacrylic adhesives, during at least a period of 90 d, and guarantees a good
      adhesion for the application of hernia repair meshes.

PMID- 27704694
TI  - Analysis of proteins and peptides by electromigration methods in microchips.
AB  - This review presents the developments and applications of microchip
      electromigration methods in the separation and analysis of peptides and proteins
      in the period 2011-mid-2016. The developments in sample preparation and
      preconcentration, microchannel material, and surface treatment are described.
      Separations by various microchip electromigration methods (zone electrophoresis
      in free and sieving media, affinity electrophoresis, isotachophoresis,
      isoelectric focusing, electrokinetic chromatography, and electrochromatography)
      are demonstrated. Advances in detection methods are reported and novel
      applications in the areas of proteomics and peptidomics, quality control of
      peptide and protein pharmaceuticals, analysis of proteins and peptides in
      biomatrices, and determination of physicochemical parameters are shown.

PMID- 27704696
TI  - EBUS may arise as an initial time saving procedure in patients who are suspected
      to have small cell lung cancer.
AB  - BACKGROUND: Small cell lung cancer (SCLC) commonly presents as hilar/mediastinal
      masses. In some occasions, conventional flexible bronchoscopy fails and a
      substantial amount of time is lost until establishing the diagnosis. OBJECTIVE:
      The aim of the study was to demonstrate the superiority of endobronchial
      ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) compared to
      conventional methods in establishing the diagnosis as an initial modality as well
      as to point out the saved time until the diagnosis. METHODS: We retrospectively
      reviewed the patients who were diagnosed as SCLC by EBUS-TBNA between April 2010
      and January 2016. The demographics of the patients, smoking history were all
      recorded. We also compared the time between the first computed tomography (1stCT)
      and first diagnostic procedure (1stDP), 1stDP and final diagnosis (FDx), 1stCT
      and FDx, and 1stDP and EBUS procedure were also compared. RESULTS: One hundred
      and thirty-three patients were included in the study. The diagnostic yield of
      EBUS-TBNA was 98.5%. The mean time between the 1stCT and 1stDP; 1stDP and FDx;
      1stCT and FDx; 1stDP and EBUS procedure were 7.0 +/- 9.0; 11.8 +/- 16.1; 18.8 +/-
      17.9; and 10.8 +/- 16.0 days, respectively. The time between 1stCT to 1stDP was
      not significantly different in patients with or without previous diagnostic
      procedures. However, the time between 1stDP to FDx and 1stCT to FDx were
      significantly higher in the patients with previous procedures (P < .001). The
      difference in time between 1stDP to FDx and 1stCT to FDx was also similar in
      patients with only hilar and/or mediastinal lesions (P = .001, P = .006,
      respectively). CONCLUSION: EBUS-TBNA may be an initial diagnostic procedure in
      SCLC. Patients with only hilar/mediastinal masses without any endobronchial
      lesion could be directed to centers with the capability for performing EBUS-TBNA
      to have a rapid diagnosis without any time loss.

PMID- 27704697
TI  - Carboxymethylinulin-Chitosan Nanoparticles for the Delivery of Antineoplastic
      Mitoxantrone.
AB  - Mitoxantrone (MTX) is an antineoplastic agent whose use is limited by serious
      side effects on non-neoplastic cells. The aim of this study was the development
      of a new drug release system using an ionotropic gelation technique for
      microencapsulation of MTX in chitosan-carboxymethylinulin nanoparticles (CCInp),
      followed by evaluation of their cytotoxic effects on neoplastic MDA-MB-231 and
      non-neoplastic NIH3T3 cell lines. The CCInp were prepared through a new reliable
      method for easy functionalization of both inulin and chitosan. Both unloaded and
      drug-loaded nanoparticles were characterized by transmission electron microscopy
      (TEM) and dynamic light scattering (DLS) and showed a spherical morphology with
      an average hydrodynamic diameter between 40 and 80 nm. Both nanoparticles were
      stable and easily degraded by lysozyme. MTX-loaded nanoparticles led to a greater
      mortality of MDA-MB-231 relative to free drug due to the ability of the
      nanoparticles to accumulate preferentially in neoplastic cells. The developed
      drug release system retains the ability to kill MDA-MB-231 cells in vitro,
      improving the survival of NIH3T3 cells.

PMID- 27704695
TI  - Weight loss after head and neck cancer: A dynamic relationship with depressive
      symptoms.
AB  - BACKGROUND: Weight loss and depressive symptoms are critical head and neck cancer
      outcomes, yet their relation over the illness course is unclear. METHODS:
      Associations between self-reported depressive symptoms and objective weight loss
      across the year after head and neck cancer diagnosis were examined using growth
      curve modeling techniques (n = 564). RESULTS: A reciprocal covariation pattern
      emerged-changes in depressive symptoms over time were associated with same-month
      changes in weight loss (t [1148] = 2.05; p = .041), and changes in weight loss
      were associated with same-month changes in depressive symptoms (t [556] = 2.43; p
      = .015). To the extent that depressive symptoms increased, patients lost
      incrementally more weight than was lost due to the passage of time and vice
      versa. Results also suggested that pain and eating-related quality of life might
      explain the reciprocal association between depressive symptoms and weight loss.
      CONCLUSION: In head and neck cancer, a transactional interplay between depressive
      symptoms and weight loss unfolds over time. (c) 2016 Wiley Periodicals, Inc. Head
      Neck 39: 370-379, 2017.

PMID- 27704698
TI  - Advances in RNA molecular dynamics: a simulator's guide to RNA force fields.
AB  - Molecular simulations have become an essential tool for biochemical research.
      When they work properly, they are able to provide invaluable interpretations of
      experimental results and ultimately provide novel, experimentally testable
      predictions. Unfortunately, not all simulation models are created equal, and with
      inaccurate models it becomes unclear what is a bona fide prediction versus a
      simulation artifact. RNA models are still in their infancy compared to the many
      robust protein models that are widely in use, and for that reason the number of
      RNA force field revisions in recent years has been rapidly increasing. As there
      is no universally accepted 'best' RNA force field at the current time, RNA
      simulators must decide which one is most suited to their purposes, cognizant of
      its essential assumptions and their inherent strengths and weaknesses. Hopefully,
      armed with a better understanding of what goes inside the simulation 'black box,'
      RNA biochemists can devise novel experiments and provide crucial thermodynamic
      and structural data that will guide the development and testing of improved RNA
      models. WIREs RNA 2017, 8:e1396. doi: 10.1002/wrna.1396 For further resources
      related to this article, please visit the WIREs website.

PMID- 27704699
TI  - A Surfactant-Encapsulating Polyoxometalate Nanowire Assembly as a New Carrier for
      Nanoscale Noble-Metal Catalysts.
AB  - The loading of noble-metal nanoparticles (NMNPs) onto various carriers to obtain
      stable and highly efficient catalysts is currently an important strategy in the
      development of noble metal (NM)-based catalytic reactions and their applications.
      We herein report a nanowire supramolecular assembly constructed from the
      surfactant-encapsulating polyoxometalates (SEPs) CTAB-PW12 , which can act as new
      carriers for NMNPs. In this case, the Ag NPs are loaded onto the SEP nanowire
      assembly with a narrow size distribution from 5 to 20 nm in diameter; the average
      size is approximately 10 nm. The Ag NPs on the nanowire assemblies are well
      stabilized and the over agglomeration of Ag NPs is avoided owing to the existence
      of well-arranged polyoxometalate (POM) units in the SEP assembly and the
      hydrophobic surfactant on the surface of the nanowire assembly. Furthermore, the
      loading amount of the Ag NPs can be adjusted by controlling the concentration of
      the AgNO3 aqueous solution. The resultant Ag/CTAB-PW12 composite materials
      exhibit high activity and good stability for the catalytic reduction of 4
      nitrophenol (4-NP) with NaBH4 in isopropanol/H2 O solution. The NMNPs-loaded SEP
      nanoassembly may represent a new composite catalyst system for application in NM
      based catalysis.

PMID- 27704700
TI  - Study of intra-racial exclusion within Australian Indigenous communities using
      eco-maps.
AB  - In Australia, 'indigeneity' is not determined by skin colour, but rather by a
      person's heritage, acceptance by an indigenous community, and active
      participation in the affairs of that indigenous community. Some people who
      identify as indigenous, however, have experienced 'colourism' - that is,
      experiences of social exclusion because of the colour of their skin - from non
      Indigenous and also Indigenous Australians. This paper describes research that
      explored the effect of intra-racial exclusion on the mental health and wellbeing
      of Indigenous Australians, with a particular focus on skin colour or 'manifest
      indigeneity'. Framed within a qualitative design, an eco-map was used to guide in
      depth interviews with 32 participants that gave rise to personal stories that
      described the distress of experiencing intra-racial colourism. Findings were
      derived from a thematic analysis that identified four major themes: 'Growing up
      black', 'Living on black country', 'Looking black', and 'Fitting in black'. These
      findings are important because they suggest a way forward for mental health
      nurses to better understand and support the mental health and wellbeing of
      Indigenous Australians who have experienced social exclusion as a result of
      colourism.

PMID- 27704701
TI  - 3D Cathodes of Cupric Oxide Nanosheets Coated onto Macroporous Antimony-Doped Tin
      Oxide for Photoelectrochemical Water Splitting.
AB  - Cupric oxide (CuO), a narrow-bandgap semiconductor, has a band alignment that
      makes it an ideal photocathode for the renewable production of solar fuels.
      However, the photoelectrochemical performance of CuO is limited by its poor
      conductivity and short electron diffusion lengths. Herein, a three-dimensional
      (3D) architecture consisting of CuO nanosheets supported onto transparent
      conducting macroporous antimony-doped tin oxide (mpATO@CuONSs) is designed as an
      excellent photocathode for promoting the hydrogen evolution reaction (HER). Owing
      to the 3D structure affording superior light-harvesting characteristics, large
      contact areas with the electrolyte, and highly conductive pathways for separation
      and transport of charge carriers, the mpATO@CuONSs photocathode produces an
      impressively high photocurrent density of -4.6 mA cm-2 at 0 V versus the
      reversible hydrogen electrode (RHE), which is much higher than that of the CuONSs
      array onto planar FTO glass (-1.9 mA cm-2 ).

PMID- 27704702
TI  - Final year Australian nursing students' experiences with bioscience: A cross
      sectional survey.
AB  - Nursing students have reported bioscience to be challenging and difficult to
      understand. This might have a negative impact upon their ability to understand
      patients' clinical conditions and nursing practice. We sought information about
      students' experiences with bioscience. A total of 126 final year nursing students
      completed a questionnaire. The findings showed that the majority of participants
      considered bioscience subjects to require more work compared to nursing subjects
      (65.9%), and that they would like a better understanding of bioscience (73.8%),
      but understood that bioscience forms the foundation of nursing practice (76.2%).
      Younger participants without secondary school science rated bioscience harder
      than nursing subjects and spent more time studying bioscience compared to older
      participants. Participants without any secondary school science lacked an ability
      to apply bioscience concepts to patient conditions. These results showed that
      nursing students, especially those without secondary school science, would
      benefit from improved bioscience integration with nursing practice. Nursing and
      bioscience educators should consider greater alignment of bioscience with nursing
      practice subjects, especially earlier in the curriculum.

PMID- 27704703
TI  - Umbilical lactate as a measure of acidosis and predictor of neonatal risk: a
      systematic review.
AB  - BACKGROUND: Umbilical cord lactate is one approach to measuring acidosis and
      intrapartum hypoxia, knowledge of which may be helpful for clinicians involved in
      the care of women and newborns. OBJECTIVE: To synthesise the evidence on accuracy
      of umbilical cord lactate in measuring acidosis and predicting poor neonatal
      outcome. SEARCH STRATEGY: Studies published and unpublished between 1990 and 2014
      from PubMed/Medline, EMBASE, Cochrane Central Register of Controlled Trials, and
      clinicaltrials.gov were assessed. SELECTION CRITERIA: Cross-sectional and
      randomised studies that assessed fetal acidosis (using lactate as the index test)
      with or without an assessment of neonatal outcome. DATA COLLECTION AND ANALYSIS:
      Correlations between index and reference test(s) were recorded, as were the raw
      data to classify the predictive ability of umbilical lactate for neonatal
      outcomes. Meta-analysis of correlation was performed. We plotted estimates of the
      studies' observed sensitivities and specificities on Forest plots with 95%
      confidence intervals (CI). Where possible, we combined data using meta-analysis,
      applying the hierarchical summary receiver operating characteristics model and a
      bivariate model. MAIN RESULTS: Twelve studies were included. Umbilical lactate
      correlated with pH [pooled effect size (ES) -0.650; 95% CI -0.663 to -0.637, P <
      0.001], base excess (ES -0.710; 95% CI -0.721 to -0.699, P < 0.001), and Apgar
      scores at 5 minutes (ES 0.300; 95% 0.193-0.407, P < 0.001). Umbilical lactate had
      pooled sensitivity and specificity for predicting neonatal neurological outcome
      including hypoxic ischaemic encephalopathy of 69.7% (95% CI 23.8-94.4%) and 93%
      (95% CI 86.8-96.3%). AUTHORS' CONCLUSION: Umbilical cord lactate is a clinically
      applicable, inexpensive and effective way to measure acidosis and is a tool that
      may be used in the assessment of neonatal outcome. TWEETABLE ABSTRACT: Umbilical
      cord lactate: a clinically applicable, inexpensive, effective way to measure
      intrapartum acidosis.

PMID- 27704704
TI  - Composite paraganglioma-ganglioneuroma concomitant with adrenal metastasis of
      medullary thyroid carcinoma in a patient with multiple endocrine neoplasia type
      2B: A case report.
AB  - Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer
      syndrome with major components of medullary thyroid carcinoma, pheochromocytoma,
      and hyperparathyroidism. MEN2B is the most aggressive and rarest of the MEN2
      variants. Pheochromocytoma in MEN2 is virtually always located in the adrenal
      medulla, but MEN2-associated extra-adrenal pheochromocytomas (paraganglioma) are
      rare. A 59-year-old man who has been diagnosed with MEN2B consulted our hospital
      for surgical treatment of a 10-mm left adrenal mass and a 30-mm retroperitoneal
      mass. He had paroxysmal elevations in blood pressure and in urinary metanephrine
      and vanillylmandelic acid values. Laparoscopic excision of the left adrenal gland
      and retroperitoneal mass was performed. We experienced an extremely rare case of
      composite paraganglioma-ganglioneuroma concomitant with adrenal metastasis of
      medullary thyroid carcinoma in a patient with MEN2B.

PMID- 27704705
TI  - The iron-sulfur cluster sensor IscR is a negative regulator of Spi1 type III
      secretion system in Salmonella enterica.
AB  - Iron-sulfur (Fe-S)-containing proteins contribute to various biological
      processes, including redox reactions or regulation of gene expression. Living
      organisms have evolved by developing distinct biosynthetic pathways to assemble
      these clusters, including iron sulfur cluster (ISC) and sulfur mobilization
      (SUF). Salmonella enterica serovar Typhimurium is an intracellular pathogen
      responsible for a wide range of infections, from gastroenteritis to severe
      systemic diseases. Salmonella possesses all known prokaryotic systems to assemble
      Fe-S clusters, including ISC and SUF. Because iron starvation and oxidative
      stress are detrimental for Fe-S enzyme biogenesis and because such environments
      are often met by Salmonella during its intracellular life, we investigated the
      role of the ISC and SUF machineries during the course of the infection. The iscU
      mutant, which is predicted to have no ISC system functioning, was found to be
      defective for epithelial cell invasion and for mice infection, whereas the sufBC
      mutant, which is predicted to have no SUF system functioning, did not present any
      defect. Moreover, the iscU mutant was highly impaired in the expression of
      Salmonella pathogenicity island 1 (Spi1) type III secretion system that is
      essential for the first stage of Salmonella infection. The Fe-S cluster sensor
      IscR, a transcriptional regulator matured by the ISC machinery, was shown to bind
      the promoter of hilD, which encodes the master regulator of Spi1. IscR was also
      demonstrated to repress hilD and subsequently Spi1 gene expression, consistent
      with the observation that an IscR mutant is hyper-invasive in epithelial cells.
      Collectively, our findings indicate that the ISC machinery plays a central role
      in Salmonella virulence through the ability of IscR to down-regulate Spi1 gene
      expression. At a broader level, this model illustrates an adaptive mechanism used
      by bacterial pathogens to modulate their infectivity according to iron and oxygen
      availability.

PMID- 27704706
TI  - Computational design and engineering of polymeric orthodontic aligners.
AB  - Transparent and removable aligners represent an effective solution to correct
      various orthodontic malocclusions through minimally invasive procedures. An
      aligner-based treatment requires patients to sequentially wear dentition-mating
      shells obtained by thermoforming polymeric disks on reference dental models. An
      aligner is shaped introducing a geometrical mismatch with respect to the actual
      tooth positions to induce a loading system, which moves the target teeth toward
      the correct positions. The common practice is based on selecting the aligner
      features (material, thickness, and auxiliary elements) by only considering
      clinician's subjective assessments. In this article, a computational design and
      engineering methodology has been developed to reconstruct anatomical tissues, to
      model parametric aligner shapes, to simulate orthodontic movements, and to
      enhance the aligner design. The proposed approach integrates computer-aided
      technologies, from tomographic imaging to optical scanning, from parametric
      modeling to finite element analyses, within a 3-dimensional digital framework.
      The anatomical modeling provides anatomies, including teeth (roots and crowns),
      jaw bones, and periodontal ligaments, which are the references for the down
      streaming parametric aligner shaping. The biomechanical interactions between
      anatomical models and aligner geometries are virtually reproduced using a finite
      element analysis software. The methodology allows numerical simulations of
      patient-specific conditions and the comparative analyses of different aligner
      configurations. In this article, the digital framework has been used to study the
      influence of various auxiliary elements on the loading system delivered to a
      maxillary and a mandibular central incisor during an orthodontic tipping
      movement. Numerical simulations have shown a high dependency of the orthodontic
      tooth movement on the auxiliary element configuration, which should then be
      accurately selected to maximize the aligner's effectiveness.

PMID- 27704707
TI  - Evaluation of a new carbon/zirconia-based sorbent for the cleanup of food
      extracts in multiclass analysis of pesticides and environmental contaminants.
AB  - A novel carbon/zirconia-based material, SupelTM QuE Verde, was evaluated in a
      filter-vial dispersive solid-phase extraction cleanup of pork, salmon, kale, and
      avocado extracts for the residual analysis of 65 pesticides and 52 environmental
      contaminants (flame retardants, polychlorinated biphenyls, polybrominated
      diphenyl ethers, and polycyclic aromatic hydrocarbons) using low-pressure gas
      chromatography with tandem mass spectrometry. An amount of 180 mg sorbent per 0.6
      mL extract in filter-vial dispersive solid-phase extraction cleanup was found the
      optimum in terms of achieving satisfactory removal of co-extractives and
      recoveries of analytes, especially for structurally planar compounds. For
      analytes partially retained by Verde, normalization to an internal standard
      resulted in 62-107% recoveries. Addition of Verde to primary secondary amine and
      C18 in cleanup resulted in 38% more removal of gas-chromatography-amenable co
      extractives in avocado, 30% in kale, 39% in salmon, and 50% in pork. The removal
      efficiency of co-extracted chlorophyll was 93% for kale and 64% for avocado based
      on ultraviolet-visible absorbance. The developed method was validated at three
      spiking levels (10, 25, and 100 ng/g), and 70-120% recoveries with <=20% relative
      standard deviation were achieved for 96 (83%) out of 117 analytes in pork, 79
      (69%) in salmon, 71 (62%) in kale, and 75 (65%) in avocado.

PMID- 27704708
TI  - Method development for separating organic carbonates by ion-moderated high
      performance liquid chromatography.
AB  - An ion-moderated partition high-performance liquid chromatography method was
      developed for the separation and identification of common organic carbonates. The
      separation of organic carbonates was achieved on an ion exclusion column with an
      exchangeable hydrogen ion. An isocratic, aqueous mobile phase was used for
      elution and detection was performed with a refractive index detector. The
      developed method was validated for specificity, linearity, limits of detection
      and quantification, precision and accuracy. All calibration curves showed
      excellent linear regression (R2 > 0.9990) within the testing range. The limits of
      detection were 3.8-30.8 ppm for the analyzed carbonates. Improvements in the peak
      resolution of the chromatograms were achieved by decreasing the column
      temperature. Addition of the organic modifier, acetonitrile, to the eluent was
      found to have insignificant effects on the peak resolution. The developed method
      was demonstrated for analyzing organic carbonate components in the electrolyte
      system of a commercial lithium ion battery.

PMID- 27704709
TI  - Comparative evaluation of the impact of minimally invasive preparation vs.
      conventional straight-line preparation on tooth biomechanics: a finite element
      analysis.
AB  - Minimally invasive endodontics emphasizes preservation of a maximal amount of
      healthy tooth tissue. However, whether the tooth structure preserved by minimally
      invasive endodontics can maintain higher fracture resistance is unclear. This
      study aimed to compare the biomechanics on teeth after minimally invasive (MI)
      preparation and straight-line (SL) preparation using finite element analysis. Six
      finite element analysis models of a mandibular first molar were constructed and
      divided into two groups (MI and SL). Two loads of 250 N, one vertically
      stimulating the vertical masticatory force and the other given 45 degrees  to the
      longitudinal axis of the tooth, were applied. Stresses in the teeth were
      calculated and analyzed. Under both vertical and 45 degrees  loads, the greatest
      stresses were located at the margin of the cavities on the occlusal surfaces. The
      stress concentration areas of teeth with minimally invasive access cavities were
      smaller than those of teeth prepared with straight-line opening in coronal and
      cervical areas. The stress concentration points in the cervical areas increased
      with the increase of canal taper in the coronal third. Minimally invasive access
      preparation reduced the stress distribution in crown and cervical regions. A
      smaller taper cervical enlargement caused lower stress in the cervical region.

PMID- 27704710
TI  - PARADIGM-HF: does dose matter?

PMID- 27704711
TI  - Heterogeneity across one disease, two drugs, three trials, and four guidelines:
      are we further ahead?

PMID- 27704712
TI  - Stroke prevention in heart failure and sinus rhythm: where do we go from here?

PMID- 27704713
TI  - October 2016 at a glance: treatment of heart failure.

PMID- 27704714
TI  - Obstetric bleeding among women with inherited bleeding disorders: a retrospective
      study.
AB  - INTRODUCTION: Women with inherited bleeding disorders are at increased risk for
      bleeding complications during pregnancy and the postpartum period, particularly
      postpartum haemorrhage (PPH). AIM: This retrospective study evaluates pregnancy
      management through the Inherited Bleeding Disorders Clinic of Southeastern
      Ontario, the clinical factors associated with pregnancy-related abnormal bleeding
      and assesses tranexamic acid use in the postpartum treatment of bleeding disorder
      patients. METHODS: A chart review of 62 pregnancies, from 33 women, evaluated
      patient characteristics (age, haemostatic factor levels) and delivery conditions
      (mode of delivery, postpartum treatment) in relation to abnormal postpartum
      bleeding. RESULTS: This cohort revealed increased risk of immediate PPH with
      increased age at delivery (mean age: 30.1 years with PPH, 26.5 years without PPH,
      P < 0.013), and birth by vaginal delivery (P < 0.042). Low von Willebrand factor
      (VWF) antigen or factor VIII (FVIII) in the third trimester was not associated
      with an increased risk of PPH; however, low VWF:RCo was associated with increased
      immediate PPH despite treatment with continuous factor infusion (P < 0.042).
      Women treated with tranexamic acid postpartum had less severe bleeding in the 6
      week postpartum (P < 0.049) with no thrombotic complications. CONCLUSIONS: This
      study contributes to the growing body of work aimed at optimizing management of
      bleeding disorder patients through pregnancy and the postpartum period, showing
      patients are at a higher risk of PPH as they age. Risk factors such as low third
      trimester VWF:RCo have been identified. Treatment with tranexamic acid in the
      postpartum period is associated with a reduced incidence of abnormal postpartum
      bleeding.

PMID- 27704715
TI  - Higher-order structure of the 30-nm chromatin fiber revealed by cryo-EM.
AB  - Genomic DNA is hierarchically packaged into chromatin in eukaryotes. As a central
      level chromatin structure between nucleosomal arrays and higher order
      organizations, 30 nm chromatin fiber, and its dynamics play a crucial role in
      regulating DNA accessibility for gene transcription. However, despite extensive
      efforts over three decades, the higher-order structure of the 30 nm chromatin
      fiber remains unresolved and controversial. We have recently reconstituted the 30
      nm chromatin fibers from 12 nucleosomal arrays in vitro in the presence of linker
      histone H1, and determined their cryo-EM structures at resolution of 11 A (Song
      et al., Science 344, 376-380). Here, we briefly reviewed the higher-order
      structure studies of chromatin fibers, mainly focusing on the insights from the
      cryo-EM structures we recently solved. (c) 2016 IUBMB Life, 68(11):873-878, 2016.

PMID- 27704716
TI  - A quasi-3D wire approach to model pulmonary airflow in human airways.
AB  - The models used for modeling the airflow in the human airways are either 0
      dimensional compartmental or full 3-dimensional (3D) computational fluid dynamics
      (CFD) models. In the former, airways are treated as compartments, and the
      computations are performed with several assumptions, thereby generating a low
      fidelity solution. The CFD method displays extremely high fidelity since the
      solution is obtained by solving the conservation equations in a physiologically
      consistent geometry. However, CFD models (1) require millions of degrees of
      freedom to accurately describe the geometry and to reduce the discretization
      errors, (2) have convergence problems, and (3) require several days to simulate a
      few breathing cycles. In this paper, we present a novel, fast-running, and robust
      quasi-3D wire model for modeling the airflow in the human lung airway. The wire
      mesh is obtained by contracting the high-fidelity lung airway surface mesh to a
      system of connected wires, with well-defined radii. The conservation equations
      are then solved in each wire. These wire meshes have around O(1000) degrees of
      freedom and hence are 3000 to 25 000 times faster than their CFD counterparts.
      The 3D spatial nature is also preserved since these wires are contracted out of
      the actual lung STL surface. The pressure readings between the 2 approaches
      showed minor difference (maximum error = 15%). In general, this formulation is
      fast and robust, allows geometric changes, and delivers high-fidelity solutions.
      Hence, this approach has great potential for more complicated problems including
      modeling of constricted/diseased lung sections and for calibrating the lung flow
      resistances through parameter inversion.

PMID- 27704717
TI  - Extracapsular dissection versus superficial parotidectomy in benign parotid gland
      tumors: The Vienna Medical School experience.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical outcome in
      patients with benign parotid gland tumors after extracapsular dissection or
      superficial parotidectomy (SP). METHODS: Eight hundred ninety-four patients with
      primary pleomorphic adenoma or Warthin's tumor were included from this study.
      Type and length of surgery, tumor size, resection margins, and complication rates
      were assessed. RESULTS: Three hundred ninety-five (44.2%) extracapsular
      dissections and 499 SPs (55.8%) were performed. The rate of positive margins was
      significantly higher in the extracapsular dissection compared to the SP group
      (29.4% vs 10.2%; p < .0001). Recurrent disease (extracapsular dissection = 7.2%
      vs SP = 2.2%; p = .0003) and permanent facial palsy were significantly more
      frequent after extracapsular dissection than SP (2.2% vs 0.6%; p = .0396).
      Significant prolonged surgery time was observed after SP (146 vs 94 minutes; p <
      .0001). CONCLUSION: Because extracapsular dissection led to a significantly
      higher percentage of permanent facial palsy, recurrent disease, and positive
      resection margins compared to SP, we recommend SP for treating benign parotid
      gland tumors. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 356-360, 2017.

PMID- 27704719
TI  - The Science of Salt: A Regularly Updated Systematic Review of the Implementation
      of Salt Reduction Interventions (November 2015 to February 2016).
AB  - The objective of this periodic review was to identify, summarize, and appraise
      studies relating to the implementation of salt reduction strategies that were
      retrieved between November 2015 and February 2016. From the established MEDLINE
      search, 56 studies were identified as relevant to the implementation of salt
      reduction initiatives. Detailed appraisal was performed on seven studies that
      evaluated the impact of salt reduction interventions. While study quality varied,
      all had one or more risks related to bias. There was consistent evidence, from
      three studies, demonstrating that setting-based structural interventions to
      improve the nutritional composition of foods were effective in reducing salt but
      mixed evidence in relation to the effectiveness of behavioral interventions. The
      development of an evaluation guidance framework that supports scientific rigor
      and external validity would aid future design and interpretation of studies
      evaluating salt reduction interventions, particularly for low-resource countries.

PMID- 27704718
TI  - HYDAMTIQ, a selective PARP-1 inhibitor, improves bleomycin-induced lung fibrosis
      by dampening the TGF-beta/SMAD signalling pathway.
AB  - Idiopathic pulmonary fibrosis is a severe disease characterized by excessive
      myofibroblast proliferation, extracellular matrix and fibrils deposition,
      remodelling of lung parenchyma and pulmonary insufficiency. Drugs able to reduce
      disease progression are available, but therapeutic results are unsatisfactory;
      new and safe treatments are urgently needed. Poly(ADP-ribose) polymerases-1 (PARP
      1) is an abundant nuclear enzyme involved in key biological processes: DNA
      repair, gene expression control, and cell survival or death. In liver and heart,
      PARP-1 activity facilitates oxidative damage, collagen deposition and fibrosis
      development. In this study, we investigated the effects of HYDAMTIQ, a potent
      PARP-1 inhibitor, in a murine model of lung fibrosis. We evaluated the role of
      PARP on transforming growth factor-beta (TGF-beta) expression and TGF-beta/SMAD
      signalling pathway in lungs. Mice were intratracheally injected with bleomycin
      and then treated with either vehicle or different doses of HYDAMTIQ for 21 days.
      Airway resistance to inflation and lung static compliance, markers of lung
      stiffness, were assayed. Histochemical and biochemical parameters to evaluate TGF
      beta/SMAD signalling pathway with alpha-smooth muscle actin (alphaSMA) deposition
      and the levels of a number of inflammatory markers (tumour necrosis factor-alpha,
      interleukin-1beta, iNOS and COX-2) were performed. Bleomycin administration
      increased lung stiffness. It also increased lung PARP activity, TGF-beta levels,
      pSMAD3 expression, alphaSMA deposition and content of inflammatory markers.
      HYDAMTIQ attenuated all the above-mentioned physiological, biochemical and
      histopathological markers. Our findings support the proposal that PARP inhibitors
      could have a therapeutic potential in reducing the progression of signs and
      symptoms of the disease by decreasing TGF-beta expression and the TGF-beta/SMAD
      transduction pathway.

PMID- 27704721
TI  - Response to 'Letter to "Application effect of sterile normal saline ice for post
      partum hemorrhage at the time of cesarean delivery: A retrospective review": Is
      it safe?'

PMID- 27704720
TI  - Quercetin suppresses lung cancer growth by targeting Aurora B kinase.
AB  - aurora B kinase is highly expressed in several cancer cells and promotes
      tumorigenesis and progression, and therefore, it is an important target for drug
      to treat tumors. Quercetin was identified to be an antitumor agent. Herein, we
      report for the first time that quercetin inhibited aurora B activities by
      directly binding with aurora B in vitro and in vivo. Ex vivo studies showed that
      quercetin inhibited aurora B activities in JB6 Cl41 cells and A549 lung cancer
      cells. Moreover, knockdown of aurora B in A549 cells decreased their
      sensitivities to quercetin. In vivo study demonstrated that injection of
      quercetin in A549 tumor-bearing mice effectively suppressed cancer growth. The
      phosphorylation of histone 3 in tumor tissues was also decreased after quercetin
      treatment. In short, quercetin can suppress growth of lung cancer cells as an
      aurora B inhibitor both in vitro and in vivo.

PMID- 27704724
TI  - Abstracts of the XXIX Congress of the Spanish Society for Clinical Pharmacology,
      19-21 October 2016, Barcelona, Spain.

PMID- 27704722
TI  - Posttranscriptional regulation of intestinal epithelial integrity by noncoding
      RNAs.
AB  - Maintenance of the gut epithelial integrity under stressful environments requires
      epithelial cells to rapidly elicit changes in gene expression patterns to
      regulate their survival, adapt to stress, and keep epithelial homeostasis.
      Disruption of the intestinal epithelial integrity occurs commonly in patients
      with various critical illnesses, leading to the translocation of luminal toxic
      substances and bacteria to the blood stream. Recently, noncoding RNAs (ncRNAs)
      have emerged as a novel class of master regulators of gene expression and are
      fundamentally involved in many aspects of gut mucosal regeneration, protection,
      and epithelial barrier function. Here, we highlight the roles of several
      intestinal epithelial tissue-specific microRNAs, including miR-222, miR-29b, miR
      503, and miR-195, and long ncRNAs such as H19 and SPRY4-IT1 in the regulation of
      cell proliferation, apoptosis, migration, and cell-to-cell interactions and also
      further analyze the mechanisms through which ncRNAs and their interactions with
      RNA-binding proteins modulate the stability and translation of target mRNAs.
      WIREs RNA 2017, 8:e1399. doi: 10.1002/wrna.1399 For further resources related to
      this article, please visit the WIREs website.

PMID- 27704723
TI  - Drospirenone-containing combined oral contraceptives and the risk of arterial
      thrombosis: a population-based nested case-control study.
AB  - OBJECTIVE: To compare the rate of arterial thromboembolism (ATE) of drospirenone
      containing COCs to that of levonorgestrel-containing COCs. DESIGN: Population
      based cohort study. SETTING: United Kingdom's Clinical Practice Research Datalink
      (CPRD), which contains clinical records for >11 million patients. POPULATION:
      Women aged 16-45 years prescribed a drospirenone- or levonorgestrel-containing
      COC between May 2002 and June 2012. METHODS: We conducted nested case-control
      analyses using risk set sampling to randomly select up to 10 controls for each
      ATE case, matched on age, cohort entry year, CPRD registration year, COC user
      type (first-time ever, new, switcher, or prevalent users), duration of COC use,
      duration of progestin-only or implantable contraceptive use, pre-cohort entry
      duration of drospirenone and levonorgestrel use, and duration of follow up. MAIN
      OUTCOME MEASURES: We used conditional logistic regression to estimate hazard
      ratios and 95% confidence intervals (CIs), adjusted for high-dimensional
      propensity scores. RESULTS: Our cohort included 339 743 women followed over a
      mean 4.4 years, during which 228 ATE cases occurred: 37 myocardial infarctions,
      170 strokes, and 21 other ATEs; overall rate: 1.5 events per 10 000 person-years
      (PYs). After adjusting for potential confounders, the hazard ratio for ATE with
      current use of drospirenone-containing COCs versus current use of levonorgestrel
      containing COCs was 0.89 (95% CI 0.35, 2.28), corresponding to a rate difference
      of -0.16 events per 10 000 PYs. CONCLUSIONS: The overall rate of ATE in this
      population is low regardless of which COC was taken. We found little evidence of
      a difference in the rate of ATE with drospirenone- versus levonorgestrel
      containing COCs. TWEETABLE ABSTRACT: Little evidence was found of a greater
      incidence of arterial thrombosis with drospirenone versus levonorgestrel
      contraceptives.

PMID- 27704725
TI  - The efficacy of valganciclovir for prevention of infections with cytomegalovirus
      and Epstein-Barr virus after kidney transplant in children.
AB  - This study evaluated the efficacy of prophylactic ValGCV in preventing CMV and
      EBV infections in a single-center pediatric kidney transplant population (2008
      2014). Therapy duration was determined according to donor/recipient serostatus.
      EBV monitoring was performed using monthly plasma PCR for 18 months post
      transplant and for CMV, monthly for 6 months after prophylaxis cessation. Data
      were collected on 35 children, median age 10.6 years. There were 15 (42.9%) and
      11 (31.4%) recipients seronegative for CMV or EBV, respectively, who received a
      kidney from a seropositive donor. Prophylaxis was ceased by 6 months in 24 (69%),
      between seven and 13 months in 10 (29%) children. Fourteen (40%) and eight (23%)
      children experienced CMV and EBV DNAemia, respectively. Ten of the 14 (71%)
      episodes of CMV DNAemia occurred in the first 6 months following cessation of
      prophylaxis. Shorter prophylaxis was associated with increased CMV DNAemia (P =
      0.044). There was an inverse correlation between adjusted ValGCV dose and EBV
      incidence/timing. Neutropenia was more common if ValGCV dosage was >=10% of the
      dose predicted (by BSA and creatinine clearance). ValGCV prevents CMV and may
      modify EBV infection risk. Frequent dosing adjustment for BSA and creatinine
      clearance is required to optimize safety and efficacy.

PMID- 27704729
TI  - Antibiotic Control Policies in South Korea, 2000-2013.
AB  - Antibiotic stewardship is a key strategy for limiting antibiotic resistance. Over
      the last decade the South Korean government has implemented a series of
      healthcare policies directed to this end, consisting of legislative separation of
      drug prescribing and dispensing, antibiotic utilization reviews, healthcare
      quality assessment, and public reporting. As a result, the proportion of
      antibiotic prescriptions for acute upper respiratory tract infections in primary
      healthcare facilities decreased from 72.9% in 2002 to 42.7% in 2013. However, no
      significant decrease in antibiotic resistance occurred over the same period in
      clinically important bacteria such as Streptococcus pneumoniae. These government
      driven policies played a pivotal role in improving antibiotic use for outpatients
      and surgical patients in South Korea. However, to achieve long-lasting successful
      outcomes, coordinated efforts and communications among the stakeholders,
      including physicians and medical societies, are needed.

PMID- 27704726
TI  - Sera of patients with spontaneous tumour regression and elevated anti-CA I
      autoantibodies change the gene expression of ECM proteins.
AB  - Spontaneous tumour regression after high-dose therapy and autologous stem cell
      transplantation is associated with the aplastic anaemia-like syndrome and the
      presence of polyclonal autoantibodies against carbonic anhydrase I (CA I). When
      tumour cells were grown in vitro in the presence of patients' sera positive for
      anti-CA I autoantibodies, their morphological pattern was altered. These changes
      were accompanied by modifications in the gene expression profile. We observed
      downregulation of genes of the basal lamina assembly (collagen type IV alpha 4,
      the laminin subunit gamma 2), the extracellular matrix (collagen type I alpha 1),
      the cytoskeleton (keratin 14 type I), the collagen triple helix repeat containing
      1 and the proto-oncogene WNT7B. On the other hand, the expression of the CA 1
      gene was increased in the tumour cells. It was also noticed that the presence of
      anti-CA I autoantibodies did not impair tumour cell proliferation and cell
      viability in vitro. These findings were observed only in the presence of
      patients' sera positive for anti-CA I autoantibodies.

PMID- 27704730
TI  - Extended-spectrum beta-Lactamase-producing Enterobacteriaceae as a Common Cause
      of Urinary Tract Infections in Sri Lanka.
AB  - BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL
      PE) are increasingly reported as pathogens in urinary tract infections (UTIs).
      However, in Sri Lanka, the clinical and molecular epidemiology of ESBL-PE
      implicated in UTIs has not been well described. MATERIALS AND METHODS: We
      conducted prospective, laboratory-based surveillance from October to December
      2013 at a tertiary care hospital in southern Sri Lanka and enrolled patients >=1
      year of age with clinically relevant UTIs due to ESBL-PE. Isolate identity,
      antimicrobial drug susceptibility, and ESBL production were determined. Presence
      of beta-lactamase genes, bla(SHV), bla(TEM), and bla(CTX-M), was identified by
      polymerase chain reaction. RESULTS: During the study period, Enterobacteriaceae
      were detected in 184 urine samples, with 74 (40.2%) being ESBL producers. Among
      47 patients with ESBL-PE who had medical records available, 38 (80.9%) had
      clinically significant UTIs. Most UTIs (63.2%) were community acquired and 34.2%
      were in patients with diabetes. Among 36 cultured ESBL-PE isolates, significant
      susceptibility (>80%) was only retained to amikacin and the carbapenems. The
      group 1 bla(CTX-M) gene was present in 90.0% of Escherichia coli isolates and all
      Klebsiella pneumoniae and Enterobacter cloacae isolates. The bla(SHV) and
      bla(TEM) genes were more common in K. pneumoniae (75% and 50%) and E. cloacae
      (50% and 50%) isolates than in E. coli (10% and 20%) isolates, respectively.
      CONCLUSION: The majority of UTIs caused by ESBL-PE were acquired in the community
      and due to organisms carrying the group 1 CTX-M beta-lactamase. Further
      epidemiologic studies of infections due to ESBL-PE are urgently needed to better
      prevent and treat these infections in South Asia.

PMID- 27704731
TI  - Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil
      Fumarate in Asian Subjects with Human Immunodeficiency Virus 1 Infection: A Sub
      Analysis of Phase 3 Clinical Trials.
AB  - The efficacy and safety of a single tablet regimen (STR) of
      elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)
      were analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naive
      and ART-experienced Asian subjects infected with human immunodeficiency virus
      (HIV)-1. Studies GS-US-236-102 and GS-US-236-103 were randomized, double-blind,
      placebo-controlled, 144-week studies conducted in ART-naive subjects, comparing
      E/C/F/TDF versus efavirenz (EFV)/F/TDF or ritonavir-boosted atazanavir (ATV+RTV)
      plus emtricitabine/tenofovir DF (F/TDF), respectively. Studies GS-US-236-115 and
      GS-US-236-121 were randomized, open-label, 96-week long conducted in ART
      experienced subjects, who switched to E/C/F/TDF from ritonavir-boosted protease
      inhibitors (PI+RTV)+F/TDF, or non-nucleoside reverse transcriptase inhibitors
      (NNRTI)+F/TDF regimens. The E/C/F/TDF appeared to have sustained efficacy and
      safety and was well tolerated in the small number of ART-naive and ART
      experienced Asian subjects.

PMID- 27704732
TI  - Multiresistant Tuberculosis and Its Paradoxical Manifestations.

PMID- 27704733
TI  - Reply: Multiresistant Tuberculosis and Its Paradoxical Manifestations.

PMID- 27704734
TI  - Are Community-Based Hospitals Safe from Carbapenem-Resistant Enterobacteriaceae
      in Korea?

PMID- 27704735
TI  - Antibiotic-Resistant Gram-Negative Bacteremia in Febrile Neutropenic Children.

PMID- 27704736
TI  - Lactate as a Biomarker for Sepsis Prognosis?

PMID- 27704737
TI  - Collaborative Pharmacokinetic-Pharmacodynamic Research for Optimization of
      Antimicrobial Therapy.

PMID- 27704738
TI  - The Revised 2016 Korean Thyroid Association Guidelines for Thyroid Nodules and
      Cancers: Differences from the 2015 American Thyroid Association Guidelines.
AB  - Increased detection of thyroid nodules using high-resolution ultrasonography has
      resulted in a world-wide increase in the incidence of differentiated thyroid
      cancer (DTC). Despite the steep increase in its incidence, the age-standardized
      mortality rate of thyroid cancer has remained stable, which leads toward a trend
      of more conservative treatment. The latest American Thyroid Association (ATA)
      guidelines for thyroid nodules and thyroid cancer revised in 2015 suggested that
      fine needle aspiration biopsy should be performed for thyroid nodules larger than
      1 cm and lobectomy might be sufficient for 1 to 4 cm intrathyroidal DTC. In
      addition, active surveillance instead of immediate surgical treatment was also
      recommended as a treatment option for papillary thyroid microcarcinoma based on
      the results of a few observational studies from Japan. The Korean Thyroid
      Association (KTA) has organized a task force team to develop revised guidelines
      for thyroid nodules and DTC after an extensive review of articles and intense
      discussion on whether we should accept the changes in the 2015 ATA guidelines.
      This paper introduces and discusses the updated major issues and differences in
      the ATA and the KTA guidelines.

PMID- 27704739
TI  - New Biological Markers of Bone Metabolism in Osteoporosis Treatment.

PMID- 27704740
TI  - Correlation of Glypican-4 Level with Basal Active Glucagon-Like Peptide 1 Level
      in Patients with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Previous studies have reported that glypican-4 (GPC4) regulates
      insulin signaling by interacting with insulin receptor and through adipocyte
      differentiation. However, GPC4 has not been studied with regard to its effects on
      clinical factors in patients with type 2 diabetes mellitus (T2DM). We aimed to
      identify factors associated with GPC4 level in T2DM. METHODS: Between January
      2010 and December 2013, we selected 152 subjects with T2DM and collected serum
      and plasma into tubes pretreated with aprotinin and dipeptidyl peptidase-4
      inhibitor to preserve active gastric inhibitory polypeptide (GIP) and glucagon
      like peptide 1 (GLP-1). GPC4, active GLP-1, active GIP, and other factors were
      measured in these plasma samples. We performed a linear regression analysis to
      identify factors associated with GPC4 level. RESULTS: The subjects had a mean age
      of 58.1 years, were mildly obese (mean body mass index [BMI], 26.1 kg/m2), had
      T2DM of long-duration (mean, 101.3 months), glycated hemoglobin 7.5%, low insulin
      secretion, and low insulin resistance (mean homeostatic model assessment of
      insulin resistance [HOMA-IR], 1.2). Their mean GPC4 was 2.0+/-0.2 ng/mL. In
      multivariate analysis, GPC4 was independently associated with age (beta=0.224,
      P=0.009), and levels of active GLP-1 (beta=0.171, P=0.049) and aspartate
      aminotransferase (AST; beta=-0.176, P=0.043) after being adjusted for other
      clinical factors. CONCLUSION: GPC4 was independently associated with age, active
      GLP-1, and AST in T2DM patients, but was not associated with HOMA-IR and BMI,
      which are well known factors related to GPC4. Further study is needed to identify
      the mechanisms of the association between GPC4 and basal active GLP-1 levels.

PMID- 27704741
TI  - Letter: The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of
      Brown Adipocytes (Endocrinol Metab 2016;31:328-35, Cheol Ryong Ku et al.).

PMID- 27704742
TI  - Response: The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity
      of Brown Adipocytes (Endocrinol Metab 2016;31:328-35, Cheol Ryong Ku et al.).

PMID- 27704744
TI  - Influence of low protein diets on gene expression of digestive enzymes and
      hormone secretion in the gastrointestinal tract of young weaned piglets.
AB  - To investigate dietary protein level effects on digestive mechanisms, weaned
      piglets were fed for 45 d with diets containing 20%, 17%, or 14% crude protein
      (CP) supplemented to meet requirements for essential amino acids. This article
      describes the influence of dietary protein on gastrointestinal hormones and
      expression of an array of digestive enzymes in the gastrointestinal tract and
      pancreas. Results indicated that there were no significant differences in
      expression of enzymes involved in carbohydrate digestion, except for maltase in
      the duodenum. In the jejunum, amylase expression in pigs fed 20% CP was much
      higher than that in pigs fed other diets (P<0.05) and maltase expression in those
      fed 17% CP was higher than that in other treatments (P<0.05). Although there were
      no remarkable differences in expression of aminopeptidase in the small intestine
      or carboxypeptidase in the pancreas (P>0.05), there was a trend towards higher
      expression of various proteases in pigs fed 17% CP. The duodenal expression of
      enteropeptidase in diets with 14% and 17% CP was significantly higher than that
      with 20% CP (P<0.05), but treatment differences did not existed in jejunum
      (P>0.05). The expression of GPR93 as a nutrient-responsive G protein-coupled
      receptor in 14% and 17% CP diets was significantly higher than that in 20% CP
      diet in the small intestine (P<0.05). The expressions of genes for pancreatic
      enzymes, lipase and elastase, were significantly higher in pigs fed diets with
      low CP, while similar trends occurred for carboxypeptidase, chymotrypsin and
      amylase. Conversely, the gastric expressions of pepsinogen A and progastricsin
      were lower with the 17% CP diet. Differences between treatments were found in the
      gastric antral contents of cholecystokinin and somatostatin: both increased in
      pigs fed 17% CP, accompanied by decreased content of motilin, which was also seen
      in plasma concentrations. These patterns were not reflected in duodenal contents.
      In general, 17% dietary CP was beneficial to the digestion of nutrient substance
      in the gastrointestinal tract.

PMID- 27704743
TI  - Research progress of the role and mechanism of extracellular signal-regulated
      protein kinase 5 (ERK5) pathway in pathological pain.
AB  - Extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen
      activated protein kinase 1 (MAPK1), is an important member of ERK family, which
      is a subfamily of the large MAPK family. ERK5 is expressed in many tissues,
      including the dorsal root ganglion (DRG) neurons and the spinal cord. In this
      review, we focus on elaborating ERK5-associated pathway in pathological pain, in
      which the ERK5/CREB (cyclic adenosine monophosphate (cAMP)-response element
      binding protein) pathway plays a crucial role in the transduction of pain signal
      and contributes to pain hypersensitivity. ERK5 activation in the spinal dorsal
      horn occurs mainly in microglia. The activation of ERK5 can be mediated by N
      methyl-D-aspartate (NMDA) receptors. We also elaborate the relationship between
      ERK5 activation and nerve growth factor-tyrosine kinase A (NGF-TrkA), and the
      connection between ERK5 activation and brain-derived neurotrophic factor (BDNF)
      in pathological pain in detail.

PMID- 27704745
TI  - Effects of yeast products on the intestinal morphology, barrier function,
      cytokine expression, and antioxidant system of weaned piglets.
AB  - The goal of this study was to evaluate the effects of a mixture of yeast culture,
      cell wall hydrolysates, and yeast extracts (collectively "yeast products," YP) on
      the performance, intestinal physiology, and health of weaned piglets. A total of
      90 piglets weaned at 21 d of age were blocked by body weight, sex, and litter and
      randomly assigned to one of three treatments for a 14-d feeding experiment,
      including (1) a basal diet (control), (2) 1.2 g/kg of YP, and (3) 20 mg/kg of
      colistin sulfate (CSE). No statistically significant differences were observed in
      average daily feed intake, average daily weight gain, or gain-to-feed ratio among
      CSE, YP, and control piglets. Increased prevalence of diarrhea was observed among
      piglets fed the YP diet, whereas diarrhea was less prevalent among those fed CSE.
      Duodenal and jejunal villus height and duodenal crypt depth were greater in the
      control group than they were in the YP or CSE groups. Intraepithelial lymphocytes
      (IEL) in the duodenal and jejunal villi were enhanced by YP, whereas IEL in the
      ileal villi were reduced in weaned piglets fed YP. Secretion of jejunal and ileal
      interleukin-10 (IL-10) was higher and intestinal and serum antioxidant indexes
      were affected by YP and CSE. In YP- and CSE-supplemented animals, serum D-lactate
      concentration and diamine oxidase (DAO) activity were both increased, and
      intestinal mRNA expressions of occludin and ZO-1 were reduced as compared to the
      control animals. In conclusion, YP supplementation in the diets of weaned piglets
      appears to increase the incidence of diarrhea and has adverse effects on
      intestinal morphology and barrier function.

PMID- 27704746
TI  - A genome-wide analysis of the ASYMMETRIC LEAVES2/LATERAL ORGAN BOUNDARIES
      (AS2/LOB) gene family in barley (Hordeum vulgare L.).
AB  - ASYMMETRIC LEAVES2/LATERAL ORGAN BOUNDARIES (AS2/LOB) genes are a family of plant
      specific transcription factors, which play an important role in the regulation of
      plant lateral organ development and metabolism. However, a genome-wide analysis
      of the AS2/LOB gene family is still not available for barley. In the present
      study, 24 AS2-like (ASL)/LOB domain (LBD) genes were identified based on the
      barley (Hordeum vulgare L.) genome sequence. A phylogenetic tree of ASL/LBD
      proteins from barley, Arabidopsis, maize, and rice was constructed. The ASL/LBD
      genes were classified into two classes, class I and class II, which were divided
      into five and two subgroups, respectively. Genes homologous in barley and
      Arabidopsis were analyzed. In addition, the structure and chromosomal locations
      of the genes were analyzed. Expression profiles indicated that barley HvASL/LBD
      genes exhibit a variety of expression patterns, suggesting that they are involved
      in various aspects of physiological and developmental processes. This genome-wide
      analysis of the barley AS2/LOB gene family contributes to our understanding of
      the functions of the AS2/LOB gene family.

PMID- 27704747
TI  - Effects of a controlled-release fertilizer on yield, nutrient uptake, and
      fertilizer usage efficiency in early ripening rapeseed (Brassica napus L.).
AB  - BACKGROUND: Nitrogen (N), phosphorous (P), and potassium (K) are critical
      nutrient elements necessary for crop plant growth and development. However,
      excessive inputs will lead to inefficient usage and cause excessive nutrient
      losses in the field environment, and also adversely affect the soil, water and
      air quality, human health, and biodiversity. METHODS: Field experiments were
      conducted to study the effects of controlled-release fertilizer (CRF) on seed
      yield, plant growth, nutrient uptake, and fertilizer usage efficiency for early
      ripening rapeseed (Xiangzayou 1613) in the red-yellow soil of southern China
      during 2011-2013. It was grown using a soluble fertilizer (SF) and the same
      amounts of CRF, such as SF1/CRF1 (3750 kg/hm2), SF2/CRF2 (3000 kg/hm2), SF3/CRF3
      (2250 kg/hm2), SF4/CRF4 (1500 kg/hm2), SF5/CRF5 (750 kg/hm2), and also using no
      fertilizer (CK). RESULTS: CRF gave higher seed yields than SF in both seasons by
      14.51%. CRF4 and SF3 in each group achieved maximum seed yield (2066.97 and
      1844.50 kg/hm2, respectively), followed by CRF3 (1929.97 kg/hm2) and SF4 (1839.40
      kg/hm2). There were no significant differences in seed yield among CK, SF1, and
      CRF1 (P>0.05). CRF4 had the highest profit (7126.4 CNY/hm2) and showed an
      increase of 12.37% in seed yield, and it decreased by 11.01% in unit fertilizer
      rate compared with SF4. The branch number, pod number, and dry matter weight
      compared with SF increased significantly under the fertilization of CRF (P<0.05).
      The pod number per plant was the major contributor to seed yield. On the other
      hand, the N, P, and K uptakes increased at first and then decreased with
      increasing the fertilizer rate at maturity, and the N, P, and K usage efficiency
      decreased with increasing the fertilizer rate. The N, P, and K uptakes and usage
      efficiencies of the CRF were significantly higher than those of SF (P<0.05). The
      N accumulation and N usage efficiency of CRF increased by an average of 13.66%
      and 9.74 percentage points, respectively, compared to SF. In conclusion, CRF
      significantly promoted the growth of rapeseed with using total N as the base
      fertilizer, by providing sufficient N in the later growth stages, and last by
      reducing the residual N in the soil and increasing the N accumulation and N usage
      efficiency.

PMID- 27704748
TI  - A study revealing the key aroma compounds of steamed bread made by Chinese
      traditional sourdough.
AB  - Aroma of Chinese steamed bread (CSB) is one of the important parameters that
      determines the overall quality attributes and consumer acceptance. However, the
      aroma profile of CSB still remains poorly understood, mainly because of relying
      on only a single method for aroma extraction in previous studies. Therefore, the
      objective of this study was to determine the volatile aroma compounds of five
      different samples of CSB using three different aroma extraction methods, namely
      solid-phase microextraction (SPME), simultaneous distillation-extraction (SDE),
      and purge and trap (P&T). All samples showed a unique aroma profile, which could
      be attributed to their unique microbial consortia. (E)-2-Nonenal and (E,E)-2,4
      decadienal were the most prevalent aromatic compounds revealed by SDE, which have
      not been reported previously, while ethanol and acetic acid proved to be the most
      dominant compounds by both SPME and P&T. Our approach of combining three
      different aroma extraction methods provided better insights into the aroma
      profile of CSB, which had remained largely unknown in previous studies.

PMID- 27704749
TI  - Visualization analysis of CRISPR/Cas9 gene editing technology studies.
AB  - The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR
      associated protein 9 (Cas9) system is an adaptive immune defense system that
      resists the invasion of viruses and plasmids heterologous genetic material in
      bacteria and archaea. Taking the literature related to gene editing technology of
      CRISPR/Cas9 from the Web of Science database from 2002 to 2015, we use the
      software CiteSpaceV to analyze co-cited literature in order to establish the
      research hotspots and fronts recently in this field by knowledge mapping.

PMID- 27704750
TI  - Detection of biological thiols based on a colorimetric method.
AB  - Biological thiols (biothiols), an important kind of functional biomolecules, such
      as cysteine (Cys) and glutathione (GSH), play vital roles in maintaining the
      stability of the intracellular environment. In past decades, studies have
      demonstrated that metabolic disorder of biothiols is related to many serious
      disease processes and will lead to extreme damage in human and numerous animals.
      We carried out a series of experiments to detect biothiols in biosamples,
      including bovine plasma and cell lysates of seven different cell lines based on a
      simple colorimetric method. In a typical test, the color of the test solution
      could gradually change from blue to colorless after the addition of biothiols.
      Based on the color change displayed, experimental results reveal that the
      percentage of biothiols in the embryonic fibroblast cell line is significantly
      higher than those in the other six cell lines, which provides the basis for the
      following biothiols-related study.

PMID- 27704752
TI  - Direct Observation of Conducting Filaments in Tungsten Oxide Based Transparent
      Resistive Switching Memory.
AB  - Transparent nonvolatile memory has great potential in integrated transparent
      electronics. Here, we present highly transparent resistive switching memory using
      stoichiometric WO3 film produced by cathodic electrodeposition with indium tin
      oxide electrodes. The memory device demonstrates good optical transmittance,
      excellent operative uniformity, low operating voltages (+0.25 V/-0.42 V), and
      long retention time (>104 s). Conductive atomic force microscopy, ex situ
      transmission electron microscopy, and X-ray photoelectron spectroscopy
      experiments directly confirm that the resistive switching effects occur due to
      the electric field-induced formation and annihilation of the tungsten-rich
      conductive channel between two electrodes. Information on the physical and
      chemical nature of conductive filaments offers insightful design strategies for
      resistive switching memories with excellent performances. Moreover, we
      demonstrate the promising applicability of the cathodic electrodeposition method
      for future resistive memory devices.

PMID- 27704751
TI  - Identification of FECH gene multiple variations in two Chinese patients with
      erythropoietic protoporphyria and a review.
AB  - Erythropoietic protoporphyria (EPP), an autosomal dominant disease, is caused by
      partial deficiency of ferrochelatase (FECH), which catalyzes the terminal step of
      heme biosynthesis because of loss-of-function mutations in the FECH gene. To
      date, only a few cases have been described in Asia. In this study, we describe
      the clinical features of two Chinese patients with EPP, with diagnosis confirmed
      by the increase of free protoporphyrin in erythrocytes, detection of plasma
      fluorescence peak at 630-634 nm, and analysis of FECH gene mutations. Using gene
      scanning, we identified a small deletion in the FECH gene (c.973 delA) in one
      proband (patient A) and a pathogenic FECH mutation (c.1232 G>T) in the other
      (patient B) and also observed some nucleotide variations (c.798 C>G, c.921 A>G,
      IVS1-23 C>T, IVS3+23 A>G, IVS9+35 C>T, and IVS3-48 T>C) in these patients. The
      family pedigree of patient A was then established by characterization of the
      genotype of the patient's relatives. We also analyzed the potential
      perniciousness of the missense mutation with bioinformatic software, Polyphen and
      Sift. In summary, Chinese EPP patients have similar manifestations to those of
      Caucasians, and identification of the Chinese FECH gene mutations expands the
      FECH genotypic spectrum and may contribute to genetic counseling.

PMID- 27704753
TI  - Screen-Printed Photochromic Textiles through New Inks Based on SiO2@naphthopyran
      Nanoparticles.
AB  - Photochromic silica nanoparticles (SiO2@NPT), fabricated through the covalent
      immobilization of silylated naphthopyrans (NPTs) based on 2H-naphtho[1,2-b]pyran
      (S1, S2) and 3H-naphtho[2,1-b]pyran (S3, S4) or through the direct adsorption of
      the parent naphthopyrans (1, 3) onto silica nanoparticles (SiO2 NPs), were
      successfully incorporated onto cotton fabrics by a screen-printing process. Two
      aqueous acrylic- (AC-) and polyurethane- (PU-) based inks were used as dispersing
      media. All textiles exhibited reversible photochromism under UV and solar
      irradiation, developing fast responses and intense coloration. The fabrics coated
      with SiO2@S1 and SiO2@S2 showed rapid color changes and high contrasts (DeltaE*ab
      = 39-52), despite presenting slower bleaching kinetics (2-3 h to fade to the
      original color), whereas the textiles coated with SiO2@S3 and SiO2@S4 exhibited
      excellent engagement between coloration and decoloration rates (coloration and
      fading times of 1 and 2 min, respectively; DeltaE*ab = 27-53). The PU-based
      fabrics showed excellent results during the washing fastness tests, whereas the
      AC-based textiles evidenced good results only when a protective transfer film was
      applied over the printed design.

PMID- 27704754
TI  - Visible and Near-Infrared Dual-Emission Carbogenic Small Molecular Complex with
      High RNA Selectivity and Renal Clearance for Nucleolus and Tumor Imaging.
AB  - Fluorescence imaging requires bioselective, sensitive, nontoxic molecular probes
      to detect the precise location of lesions for fundamental research and clinical
      applications. Typical inorganic semiconductor nanomaterials with large sizes (>10
      nm) can offer high-quality fluorescence imaging due to their fascinating optical
      properties but are limited to low selectivity as well as slow clearance pathway.
      We here report an N- and O-rich carbogenic small molecular complex (SMC, MW <
      1000 Da) that exhibits high quantum yield (up to 80%), nucleic acid-binding
      enhanced excitation-dependent fluorescence (EDF), and a near-infrared (NIR)
      emission peaked at 850 nm with an ultralarge Stokes shift (~500 nm). SMCs show
      strong rRNA affinity, and the resulting EDF enhancement allows multicolor
      visualization of nucleoli in cells for clear statistics. Furthermore, SMCs can be
      efficiently accumulated in tumor in vivo after injection into tumor-bearing mice.
      The NIR emission affords high signal/noise ratio imaging for delineating the true
      extent of tumor. Importantly, about 80% of injected SMCs can be rapidly excreted
      from the body in 24 h. No appreciable toxicological responses were observed up to
      30 days by hematological, biochemical, and pathological examinations. SMCs have
      great potential as a promising nucleolus- and tumor-specific agent for medical
      diagnoses and biomedical research.

PMID- 27704755
TI  - Novel Composite PEM with Long-Range Ionic Nanochannels Induced by Carbon
      Nanotube/Graphene Oxide Nanoribbon Composites.
AB  - In the current study, carbon nanotube/graphene oxide nanoribbon (CNT/GONR)
      composites were obtained via a chemical "unzipping" method. Then novel CNT/GONR
      Nafion composite proton exchange membranes (PEMs) were prepared via a blending
      method. The CNT/GONR nanocomposites induce the adjustment of (-SO3-)n ionic
      clusters in Nafion matrix to construct long-range ionic nanochannels and keep the
      activity of ionic clusters at the same time. This dramatically promotes the
      proton transport of the CNT/GONR Nafion composite PEMs at low humidity and high
      temperature. The proton conductivity of the composite PEM with 0.5 wt % CNT/GONR
      is as high as 0.18 S.cm-1 at 120  degrees C and 40%RH, nine times of recast
      Nafion (0.02 S.cm-1) at the same conditions. The 1D/2D nanostructure of CNT/GONR
      nanocomposite also contributes to restrain the methanol permeability of CNT/GONR
      Nafion. The composite PEM shows a one-order-of-magnitude decrease (2.84 * 10-09
      cm2.s-1) in methanol permeability at 40  degrees C. Therefore, incorporation of
      this 1D/2D nanocomposite into Nafion PEM is a feasible pathway to conquer the
      trade-off effect between proton conductivity and methanol resistance.

PMID- 27704756
TI  - Highly Modified Cellulose Nanocrystals and Formation of Epoxy-CNC Nanocomposites.
AB  - This work presents an environmentally friendly, iodine-catalysed chemical
      modification method to generate highly hydrophobic, optically active cellulose
      nanocrystals (CNC). The high degree of ester substitution (DS=2.18),
      hydrophobicity, crystalline behaviour and optical activity of the generated
      acetylated CNC (Ac-CNC) were quantified by TEM, FTIR, solid 13C NMR, contact
      angle, XRD and POM analyses. Ac-CNC possessing substantial enhancement in thermal
      stability (16.8%) and forms thin films with interlayer distance of 50-150 nm,
      presenting cavities suitable for entrapping nano and micro particles. Generated
      Ac-CNC proved as an effective reinforcing agent in hydrophobic polymer matrices
      for fabricating high performance nanocomposites. When integrated at a very low
      weight percentage (0.5%) in an epoxy matrix, Ac-CNC provided for a 73% increase
      in tensile strength and a 98% increase in modulus, demonstrating its remarkable
      reinforcing potential and effective stress transfer behaviour. The method of
      modification and the unique properties of the modified CNC (hydrophobicity,
      crystallinity, reinforcing ability and optical activity) render them a novel
      bionanomaterial for a range of multipurpose applications.

PMID- 27704757
TI  - Antibacterial and Anti-Inflammatory pH-Responsive Tannic Acid-Carboxylated
      Agarose Composite Hydrogels for Wound Healing.
AB  - pH-sensitive hydrogels play an important role in controlled drug release
      applications and have the potential to impact the management of wounds. In this
      study, we report the fabrication of novel carboxylated agarose/tannic acid
      hydrogel scaffolds cross-linked with zinc ions for the pH-controlled release of
      tannic acid. The resulting hydrogels exhibited negligible release of tannic acid
      at neutral and alkaline pH and sustained release at acidic pH, where they also
      displayed maximum swelling. The hydrogels also displayed favorable antibacterial
      and anti-inflammatory properties, and a lack of cytotoxicity toward 3T3
      fibroblast cell lines. In simulated wound assays, significantly greater cell
      migration and proliferation was observed for cells exposed to tannic acid
      hydrogel extracts. In addition, the tannic acid hydrogels were able to suppress
      NO production in stimulated human macrophages in a concentration-dependent
      manner, indicating effective anti-inflammatory activity. Taken together, the
      cytocompatibility, antibacterial, and anti-inflammatory characteristics of these
      novel pH-sensitive hydrogels make them promising candidates for wound dressings.

PMID- 27704758
TI  - Additively Manufactured Macroporous Titanium with Silver-Releasing Micro
      /Nanoporous Surface for Multipurpose Infection Control and Bone Repair - A Proof
      of Concept.
AB  - Restoring large-scale bone defects, where osteogenesis is slow while infections
      lurk, with biomaterials represents a formidable challenge in orthopedic clinics.
      Here, we propose a scaffold-based multipurpose anti-infection and bone repairing
      strategy to meet such restorative needs. To do this, personalized multifunctional
      titanium meshes were produced through an advanced additive manufacturing process
      and dual "TiO2-poly(dopamine)/Ag (nano)" post modifications, yielding macroporous
      constructs with micro-/nanoporous walls and nanosilver bullets
      immobilized/embedded therein. Ultrahigh loading capacity and durable release of
      Ag+ were accomplished. The scaffolds were active against planktonic/adherent
      bacteria (Gram-negative and positive) for up to 12 weeks. Additionally, they not
      only defended themselves from biofilm colonization but also helped destroy
      existing biofilms, especially in combination with antibiotics. Further, the
      osteoblasts/bacteria coculture study displayed that the engineered surfaces aided
      MG-63 cells to combat bacterial invasion. Meanwhile, the scaffolds elicited
      generally acceptable biocompatibility (cell adhesion, proliferation, and
      viability) and hastened osteoblast differentiation and maturation (alkaline
      phosphatase production, matrix secretion, and calcification), by synergy of micro
      /nanoscale topological cues and bioactive catecholamine chemistry. Although done
      ex vivo, these studies reveal that our three-in-one strategy (infection
      prophylaxis, infection fighting, and bone repair) has great potential to
      simultaneously prevent/combat infections and bridge defected bone. This work
      provides new thoughts to the use of enabling technologies to design biomaterials
      that resolve unmet clinical needs.

PMID- 27704759
TI  - Thermally Conductive, Electrical Insulating, Optically Transparent Bi-Layer
      Nanopaper.
AB  - Cellulose nanofiber (CNF) from abundant and renewable wood is an emerging
      material with excellent mechanical, chemical, and optical properties. Transparent
      nanopaper made of CNF (CNF-nanopaper) could potentially replace plastics in
      electronics due to its excellent optical transparency, mechanical strength, and
      biodegradability. However, CNF-nanopaper normally has a low thermal conductivity
      and poor stability in increasing temperatures, which is not suitable for long
      term stability and reliability in devices. Herein, for the first time, we report
      a thermally conductive, electrically insulating, and optically transparent
      nanopaper using a bilayer design where a thin layer of boron nitride (BN)
      nanosheets were coated on the CNF-nanopaper. An optical transparency (70%) and a
      thermal conductivity (0.76 W/m/K) were successfully achieved through a solution
      based process at room temperature. Such an optically transparent, electrically
      insulating, and thermally conductive bilayer nanopaper can find applications in a
      range of electronic devices.

PMID- 27704760
TI  - Crack/Fold Hybrid Structure-Based Fluidic Networks Inspired by the Epidermis of
      Desert Lizards.
AB  - A bioinspired fluidic system with cracks and folds was introduced to emulate the
      structures and functions of desert lizards' integuments, which show marked
      ability of water management. Because there was a structural analogy between
      scales and interscalar channels of lizard's skin and cracks and folds of a
      bilayer elastic material, we can mimic lizard's skin by controlling the stress
      distribution on patterned elastomers. Our system showed not only capillary-driven
      water retention within confined fluidic network, but also stretching-driven
      biaxial water transport. Observed features of our system may enhance
      understanding of water management in relation to morphogenetic aspects of
      lizards.

PMID- 27704761
TI  - Analysis of Zinc Nitride Resistive Indicators under Different Relative Humidity
      Conditions.
AB  - Zinc nitride (Zn3N2) is a metastable material in ambient conditions because of
      its high reactivity with water molecules. In this work we perform a systematic
      analysis of the oxidation of Zn3N2 layers grown by RF magnetron sputtering at
      room temperature. The aging and transformation of the layers toward a ZnO film is
      explored by means of spectroscopic ellipsometry and scanning electron microscopy
      for conditions with different relative humidity (RH). Accurate depth profiling by
      means of elastic recoil detection analysis with a time-of-flight telescope
      demonstrated the substitutional reaction between O and N and the important effect
      of the RH in this process. Because of this metastability the resistivity of the
      layers changes several orders of magnitude. Taking advantage of this principle,
      we develop electronic indicators and characterize the transformation of their
      electrical properties as a function of the ambient RH, finding a good correlation
      between the transformation time and the RH level.

PMID- 27704762
TI  - Applications of Novel Carbon/AlPO4 Hybrid-Coated H2Ti12O25 as a High-Performance
      Anode for Cylindrical Hybrid Supercapacitors.
AB  - The hybrid supercapacitor using carbon/AlPO4 hybrid-coated H2Ti12O25/activated
      carbon is fabricated as a cylindrical cell and investigated against
      electrochemical performances. The hybrid coating shows that the conductivity for
      the electron and Li ion is superior and it prevented active material from HF
      attack. Consequently, carbon/AlPO4 hybrid-coated H2Ti12O25 shows enhanced rate
      capability and long-term cycle life. Also, the hybrid coating inhibits swelling
      phenomenon caused by gas generated as decomposition reaction of electrolyte.
      Therefore, the hybrid supercapacitor using carbon/AlPO4 hybrid-coated
      H2Ti12O25/activated carbon can be applied to an energy storage system that
      requires a long-term life.

PMID- 27704764
TI  - Synthesis and Adsorption Properties of Hierarchically Ordered Nanostructures
      Derived from Porous CaO Network.
AB  - Using the porous framework of CaO as templates and reagents, we explored a
      surfactant-free and economical method for preparing calcium silicate hydrate
      (CSH) hierarchically ordered nanostructures. Incorporation of SiO2 nanoparticles
      into the CaO framework, followed by a reaction assisted by hydrothermal
      treatment, resulted in the formation of CSH with well-defined morphologies. The
      structural features of CSH were characterized by 3-D hierarchical networks,
      wherein nanofibers assembled to form nanosheets, and nanosheets assembled to form
      hierarchically ordered structures. Investigation of the crystal growth mechanism
      indicated that the key to forming the CSH ordered assembly structure was
      confining the Ca/Si ratio within a small range. Nonclassic oriented aggregation
      mechanism was used to describe the crystal growth of nanosheets, while the porous
      CaO framework served as template/reagents responsible for the formation of
      hierarchical structures. The resulting CSH adsorbent exhibited better performance
      in removing Pb(II) compared with other types of random CSH adsorbents.
      Additionally, the hierarchical structure of CSH provided more pores and active
      sites as support for other active functional materials such as zerovalent iron
      (Fe0). As-produced CSH@Fe nanocomposite with self-supported structures displayed
      high capacities for removal of Pb(II) after five adsorption-desorption cycles,
      and high capacities for other heavy metal ions (Cu2+, Cd2+, and Cr2O72-) and
      organic contaminants.

PMID- 27704763
TI  - Impact of Fullerene Mixing Behavior on the Microstructure, Photophysics, and
      Device Performance of Polymer/Fullerene Solar Cells.
AB  - Here, a comprehensive study of the influence of polymer:fullerene mixing behavior
      on the performance, thin-film microstructure, photophysics, and device physics of
      polymer solar cells is presented. In particular, blends of the donor polymer
      PBDTTT-EFT with the acceptor PC71BM that exhibit power conversion efficiencies
      over 9% are investigated. Through tuning of the fullerene concentration in PBDTTT
      EFT:PC71BM blends, the impact of fullerene mixing behavior is systematically
      investigated via a combination of synchrotron-based X-ray scattering and
      spectroscopy techniques. The impact of fullerene loading on photophysics and
      device physics is further explored with steady-state photoluminescence
      measurements, ultrafast transient absorption spectroscopy, and transient
      photovoltage measurements. In the low fullerene concentration regime (<50 wt %),
      most fullerene molecules are dispersed in the polymer matrix, resulting in severe
      geminate and nongeminate recombination due to a lack of pure fullerene aggregates
      and percolating pathways for charge separation and transport. In the high
      fullerene concentration regime (>70 wt %), large fullerene domains result in
      incomplete PC71BM exciton harvesting with the presence of fullerene molecules
      also disrupting the molecular packing of polymer crystallites. The optimum
      fullerene concentration of ~60-67 wt % balances the requirements of charge
      generation and charge collection. These findings demonstrate that controlling the
      fullerene concentration in the mixed phase and optimizing the balance between
      pure and mixed phases are critical for maximizing the efficiency of highly mixed
      polymer/fullerene solar cells.

PMID- 27704765
TI  - Impact of Covalent Functionalization on the Aqueous Processability, Catalytic
      Activity, and Biocompatibility of Chemically Exfoliated MoS2 Nanosheets.
AB  - Chemically exfoliated MoS2 (ce-MoS2) has emerged in recent years as an attractive
      two-dimensional material for use in relevant technological applications, but
      fully exploiting its potential and versatility will most probably require the
      deployment of appropriate chemical modification strategies. Here, we demonstrate
      that extensive covalent functionalization of ce-MoS2 nanosheets with acetic acid
      groups (~0.4 groups grafted per MoS2 unit) based on the organoiodide chemistry
      brings a number of benefits in terms of their processability and functionality.
      Specifically, the acetic acid-functionalized nanosheets were furnished with long
      term (>6 months) colloidal stability in aqueous medium at relatively high
      concentrations, exhibited a markedly improved temporal retention of catalytic
      activity toward the reduction of nitroarenes, and could be more effectively
      coupled with silver nanoparticles to form hybrid nanostructures. Furthermore, in
      vitro cell proliferation tests carried out with murine fibroblasts suggested that
      the chemical derivatization had a positive effect on the biocompatibility of ce
      MoS2. A hydrothermal annealing procedure was also implemented to promote the
      structural conversion of the functionalized nanosheets from the 1T phase that was
      induced during the chemical exfoliation step to the original 2H phase of the
      starting bulk material, while retaining at the same time the aqueous colloidal
      stability afforded by the presence of the acetic acid groups. Overall, by
      highlighting the benefits of this type of chemical derivatization, the present
      work should contribute to strengthen the position of ce-MoS2 as a two-dimensional
      material of significant practical utility.

PMID- 27704766
TI  - Experimental Studies on A New Fluorescent Ensemble of Calix[4]pyrrole and Its
      Sensing Performance in the Film State.
AB  - The supramolecular approach plays a pivotal role in the construction of smart and
      functional materials due to the reversible nature of noncovalent interactions. In
      the present work, two compounds, cholesterol-functionalized calix[4]pyrrole (CCP)
      and perylene bisimide diacid (PDA), were synthesized. Little fluorescence is
      observed in the ethanol solution of the mixture of CCP and PDA, while the
      solution turns fluorescent upon introduction of ammonia, which is attributed to
      the formation of a supramolecular ensemble, PDA/(CCP)2/NH3. The fluorescence
      emission of the as-formed ensemble is sensitive to the presence of phenol, an
      electron-rich analyte. Interestingly, the sensing can also be observed in the
      film state, and the relevant detection limit (DL) is lower than 1 ppb. Moreover,
      the sensing could also be performed in a visualized manner. Upon the basis of the
      findings, a sensor device with instant response and good reversibility was
      developed. Further studies revealed that the as-developed fluorescent ensemble is
      also sensitive to the presence of TNT, an electron-poor compound. The DL for this
      sensing is ~80 nM. To our knowledge, this is the first report that a fluorescent
      sensor could be used for phenol sensing in the vapor state, and for sensing of
      both electron-rich and electron-poor analytes in solution state. It is believed
      that the present study presents a distinctive example that demonstrates how smart
      sensing is realized via combination of the host-guest chemistry of
      calix[4]pyrrole and the aggregation and disaggregation property of PBI
      derivatives.

PMID- 27704768
TI  - The Optimization of Bioorthogonal Epitope Ligation within MHC-I Complexes.
AB  - Antigen recognition followed by the activation of cytotoxic T-cells (CTLs) is a
      key step in adaptive immunity, resulting in clearance of viruses and cancers. The
      repertoire of peptides that have the ability to bind to the major
      histocompatibility type-I (MHC-I) is enormous, but the approaches available for
      studying the diversity of the peptide repertoire on a cell are limited. Here, we
      explore the use of bioorthogonal chemistry to quantify specific peptide-MHC-I
      complexes (pMHC-I) on cells. We show that modifying epitope peptides with
      bioorthogonal groups in surface accessible positions allows wild-type-like MHC-I
      binding and bioorthogonal ligation using fluorogenic chromophores in combination
      with a Cu(I)-catalyzed Huisgen cycloaddition reaction. We expect that this
      approach will make a powerful addition to the antigen presentation toolkit as for
      the first time it allows quantification of antigenic peptides for which no
      detection tools exist.

PMID- 27704769
TI  - Mechanically Tunable, Readily Processable Ion Gels by Self-Assembly of Block
      Copolymers in Ionic Liquids.
AB  - Room temperature ionic liquids are of great interest for many advanced
      applications, due to the combination of attractive physical properties with
      essentially unlimited tunability of chemical structure. High chemical and thermal
      stability, favorable ionic conductivity, and complete nonvolatility are just some
      of the most important physical characteristics that make ionic liquids promising
      candidates for emerging technologies. Examples include separation membranes,
      actuators, polymer gel electrolytes, supercapacitors, ion batteries, fuel cell
      membranes, sensors, printable plastic electronics, and flexible displays.
      However, in these and other applications, it is essential to solidify the ionic
      liquid, while retaining the liquid state properties of interest. A broadly
      applicable solidification strategy relies on gelation by addition of suitable
      triblock copolymers with the ABA architecture, producing ion gels or ionogels. In
      this paradigm, the A end blocks are immiscible with the ionic liquid, and
      consequently self-assemble into micellar cores, while some fraction of the well
      solvated B midblocks bridge between micelles, forming a percolating network. The
      chemical structures of the A and B repeat units, the molar mass of the blocks,
      and the concentration of the copolymer in the ionic liquid are all independently
      tunable to attain desired property combinations. In particular, the modulus of
      the resulting ion gel can be readily varied between 100 Pa and 1 MPa, with little
      sacrifice of the transport properties of the ionic liquid, such as ionic
      conductivity or gas diffusivity. Suitable A blocks can impart thermoreversible
      gelation (with solidification either on heating or cooling) or even
      photoreversible gelation. By virtue of the nonvolatility of ionic liquids, a wide
      range of processing strategies can be employed directly to prepare ion gels in
      thin or thick film forms, including solvent casting, spin coating, aerosol jet
      printing, photopatterning, and transfer printing. For higher modulus ion gels it
      is even possible to employ a manual "cut and stick" strategy for easy device
      fabrication. Ion gels prepared from common triblock copolymers, for example, with
      A = polystyrene and B = poly(ethylene oxide) or poly(methyl methacrylate), in
      imidazolium based ionic liquids provide exceptional performance in membranes for
      separating CO2 from N2 or CH4. The same materials also are the best available
      gate dielectrics for printed plastic electronics, because their high capacitance
      endows organic transistors with milliamp output currents for sub-1 V applied
      bias, with switching speeds that can go well beyond 100 kHz, while being amenable
      to large area roll-to-roll printing. Incorporation of well-designed
      electroluminescent (e.g., Ru(bpy)3-based) or electrochromic (e.g., viologen
      based) moieties into ion gels held between transparent electrodes yields flexible
      color displays operating with sub-1 V dc inputs.

PMID- 27704767
TI  - Boc3Arg-Linked Ligands Induce Degradation by Localizing Target Proteins to the
      20S Proteasome.
AB  - Targeted protein degradation is a promising strategy for drug design and
      functional assessment. Several small molecule approaches have been developed that
      localize target proteins to ubiquitin ligases, inducing ubiquitination and
      subsequent degradation by the 26S proteasome. We discovered that the degradation
      of a target protein can also be induced by a recognition ligand linked to tert
      butyl carbamate (Boc3)-protected arginine (B3A). Here, we show that this process
      requires the proteasome but does not involve ubiquitination of the target
      protein. B3A does not perturb the structure of the target protein; instead, a B3A
      ligand stabilizes its target protein. B3A ligands stimulate activity of purified
      20S proteasome, demonstrating that the tag binds directly to the 20S proteasome.
      Moreover, purified 20S proteasome is sufficient to degrade target proteins in the
      presence of their respective B3A-linked recognition ligands. These observations
      suggest a simple model for B3A-mediated degradation wherein the B3A tag localizes
      target proteins directly to the 20S proteasome. Thus, B3A ligands are the first
      example of a ubiquitin-free strategy for targeted protein degradation.

PMID- 27704770
TI  - Spontaneous Uphill Movement and Self-Removal of Condensates on Hierarchical Tower
      Like Arrays.
AB  - Fast removal of condensates from surfaces is of great significance due to the
      enhancing thermal transfer coefficient and continuous condensation. But the
      losing super-hydrophobicity of lotus leaves questions us what kind of surface
      morphologies meets the self-removal of condensates? The uphill movement of
      condensates in textured surfaces is vital to avoiding flood and facilitating self
      removal. Here, super-hydrophobic micro-tower arrays were designed to explore the
      spontaneous uphill movement and Wenzel to Cassie transition as well as the self
      removal of condensates. The tower-like arrays enable spontaneous uphill movement
      of tiny condensates entrapped in microstructures due to the large upward Laplace
      pressure which is ~30 times larger than that on cone-like arrays. The sharp tips
      decrease the adhesion to suspending droplets and promote their fast self-removal.
      These results are important for designing desirable textured surfaces by
      enlarging upward Laplace pressure to facilitate condensates self-removal, which
      are widely applied in self-cleaning, anti-fogging, anti-icing, water harvesting
      and thermal management systems.

PMID- 27704771
TI  - Distinguishing between Leucine and Isoleucine by Integrated LC-MS Analysis Using
      an Orbitrap Fusion Mass Spectrometer.
AB  - Despite the great success of mass spectrometry (MS) for de novo protein
      sequencing, Leu and Ile have been generally considered to be indistinguishable by
      MS because their molecular masses are exactly the same. Positioning of incorrect
      Leu/Ile residues in variable domains, especially in CDRs (complementarity
      determining regions) of an antibody, may result in substantial loss of antigen
      binding affinity and specificity of the antibody. Here, we describe an integrated
      LC-MS based strategy, encompassing a combination of HCD (high-energy collisional
      dissociation) multistage mass spectrometric analysis (HCD-MSn) and ETD (electron
      transfer dissociation)-HCD MS3 analysis using an Orbitrap Fusion mass
      spectrometer, to reliably identify Leu and Ile residues in proteins and peptides.
      The merits and limitations of this Leu/Ile discrimination approach are evaluated.
      Using the new approach, along with proposed decision-making guidelines we
      unambiguously identified every Leu/Ile residue in peptides containing up to five
      Leu/Ile residues and molecular masses up to 3000 Da. In addition, we have
      demonstrated, for the first time, that every Leu/Ile residue in the variable
      regions of a monoclonal antibody that could not be assigned by antibody germline
      sequence alignment could be correctly determined using this approach. Our results
      suggest that, by incorporating this approach into existing de novo antibody
      sequencing protocols, 100% of antibody amino acid sequences, including identity
      of Leu and Ile residues, can be accurately obtained solely by means of mass
      spectrometry. In principle, this integrated, online LC-MS approach for Leu/Ile
      assignment can be applied to de novo sequencing of any protein or peptide.

PMID- 27704773
TI  - Controlling the Polarization State of Light with Plasmonic Metal Oxide
      Metasurface.
AB  - Conventional plasmonic materials, namely noble metals, hamper the realization of
      practical plasmonic devices due to their intrinsic limitations, such as lack of
      capabilities to tune in real-time their optical properties, failure to assimilate
      with CMOS-standards, and severe degradation at elevated temperatures. Transparent
      conducting oxides (TCOs) is a promising alternative as plasmonic material
      throughout the near- and mid-infrared wavelengths. In addition to compatibility
      with established silicon-based fabrication procedures, TCOs provide great
      flexibility in the design and optimization of plasmonic devices since their
      intrinsic optical properties can be tailored and dynamically tuned. In this work,
      we experimentally demonstrate metal-oxide metasurfaces operating as quarter-wave
      plates (QWP) over a broad near infrared (NIR) range from 1.75 to 2.50 um. We
      employ zinc oxide highly doped with gallium (Ga:ZnO) as the plasmonic constituent
      material of the metasurfaces, and fabricate arrays of orthogonal nanorod pairs.
      Our Ga:ZnO metasurfaces provide a high degree of circular polarization across a
      broad range of two distinct optical bands in the NIR. Flexible broadband
      tunability of the QWP metasurfaces is achieved by the significant shifts of their
      optical bands, and without any degradation in their performance, after a post
      annealing process up to 450  degrees C.

PMID- 27704772
TI  - Zika Virus: Emergence, Phylogenetics, Challenges, and Opportunities.
AB  - Zika virus (ZIKV) is an emerging arthropod-borne pathogen that has recently
      gained notoriety due to its rapid and ongoing geographic expansion and its novel
      association with neurological complications. Reports of ZIKV-associated Guillain
      Barre syndrome as well as fetal microcephaly place emphasis on the need to
      develop preventative measures and therapeutics to combat ZIKV infection. Thus, it
      is imperative that models to study ZIKV replication and pathogenesis and the
      immune response are developed in conjunction with integrated vector control
      strategies to mount an efficient response to the pandemic. This paper summarizes
      the current state of knowledge on ZIKV, including the clinical features,
      phylogenetic analyses, pathogenesis, and the immune response to infection.
      Potential challenges in developing diagnostic tools, treatment, and prevention
      strategies are also discussed.

PMID- 27704774
TI  - Characterization of Few-Layer 1T' MoTe2 by Polarization-Resolved Second Harmonic
      Generation and Raman Scattering.
AB  - We study the crystal symmetry of few-layer 1T' MoTe2 using the polarization
      dependence of the second harmonic generation (SHG) and Raman scattering. Bulk 1T'
      MoTe2 is known to be inversion symmetric; however, we find that the inversion
      symmetry is broken for finite crystals with even numbers of layers, resulting in
      strong SHG comparable to other transition metal dichalcogenides. Group theory
      analysis of the polarization dependence of the Raman signals allows for the
      definitive assignment of all the Raman modes in 1T' MoTe2 and clears up a
      discrepancy in the literature. The Raman results were also compared with density
      functional theory simulations and are in excellent agreement in the layer
      depenent variations of the Raman modes. The experimental measurements also
      determine the relationship between the crystal axes and the polarization
      dependence of the SHG and Raman scattering, which now allows the anisotropy of
      polarized SHG or Raman signal to independently determine the crystal orientation.

PMID- 27704776
TI  - Controllable Laser Reduction of Graphene Oxide Films for Photoelectronic
      Applications.
AB  - This article presents a new simple method of creating light-absorbing carbon
      material for optical devices such as bolometers. A simple method of laser
      microstructuring of graphene oxide is used in order to create such material. The
      absorption values of more than 98% in the visible and more than 90% in the
      infrared range are achieved. Moreover thermal properties of the films, such as
      temperature dependence and the thermal response of the samples, are studied. The
      change in resistance with temperature is 13 Ohm K-1, temperature coefficient of
      resistance (TCR) is 0.3% K-1, and the sensitivity is 0.17 V W-1 at 300 K. Thermal
      conductivity is rather high at ~104 W m-1 K-1 at 300 K. The designed bolometer
      operates at room temperature using incandescent lamp as a light source. This
      technique suggests a new inexpensive way to create a selective absorption coating
      and/or active layer for optical devices. Developed GO and rGO films have a large
      surface area and high conductivity. These properties make carbon coatings a
      perfect candidate for creating a new type of optoelectronic devices (gas sensors,
      detectors of biological objects, etc.).

PMID- 27704775
TI  - Rational Design of Dual Agonist-Antibody Fusions as Long-acting Therapeutic
      Hormones.
AB  - Recent studies have suggested that modulation of two or more signaling pathways
      can achieve substantial weight loss and glycemic stability. We have developed an
      approach to the generation of bifunctional antibody agonists that activate leptin
      receptor and GLP-1 receptor. Leptin was fused into the complementarity
      determining region 3 loop of the light chain alone, or in combination with
      exendin-4 (EX4) fused at the N-terminus of the heavy chain of Herceptin. The
      antibody fusions exhibit similar or increased in vitro activities on their
      cognate receptors, but 50-100-fold longer circulating half-lives in rodents
      compared to the corresponding native peptides/proteins. The efficacy of the
      leptin/EX4 dual antibody fusion on weight loss, especially fat mass loss, was
      enhanced in ob/ob mice and DIO mice compared to the antibody fusion of either EX4
      or leptin alone. This work demonstrates the versatility of this combinatorial
      fusion strategy for generating dual antibody agonists with long half-lives.

PMID- 27704777
TI  - Nanoscale-Barrier Formation Induced by Low-Dose Electron-Beam Exposure in
      Ultrathin MoS2 Transistors.
AB  - Utilizing an innovative combination of scanning-probe and spectroscopic
      techniques, supported by first-principles calculations, we demonstrate how
      electron-beam exposure of field-effect transistors, implemented from ultrathin
      molybdenum disulfide (MoS2), may cause nanoscale structural modifications that in
      turn significantly modify the electrical operation of these devices. Quite
      surprisingly, these modifications are induced by even the relatively low electron
      doses used in conventional electron-beam lithography, which are found to induce
      compressive strain in the atomically thin MoS2. Likely arising from sulfur
      vacancy formation in the exposed regions, the strain gives rise to a local
      widening of the MoS2 bandgap, an idea that is supported both by our experiment
      and by the results of first-principles calculations. A nanoscale potential
      barrier develops at the boundary between exposed and unexposed regions and may
      cause extrinsic variations in the resulting electrical characteristics exhibited
      by the transistor. The widespread use of electron-beam lithography in
      nanofabrication implies that the presence of such strain must be carefully
      considered when seeking to harness the potential of atomically thin transistors.
      At the same time, this work also promises the possibility of exploiting the
      strain as a means to achieve "bandstructure engineering" in such devices.

PMID- 27704778
TI  - Functional Packaging of Lateral Flow Strip Allows Simple Delivery of Multiple
      Reagents for Multistep Assays.
AB  - This paper presents a rotary device designed for facile delivery of multiple
      reagents to a paper strip for multistep assays. Its purpose is to allow users to
      easily perform multistep assays and achieve sensitive detection. While the test
      strip remains stationary, rotating the top piece of the device aligns the reagent
      and absorbent pads to each end of the paper strip and initiates fluid flow.
      Further incremental rotation makes an adjacent pair of pads to align
      simultaneously, causing fluid flow of subsequent reagent that was preloaded in
      the reagent pad. In this work, various porous substrates were tested to observe
      their effect on overall flow rate of the system and multistep assays were
      performed to demonstrate its simple use. As a proof of concept, enzyme-linked
      immunosorbent assay was carried out to detect Escherichia coli O157:H7.

PMID- 27704779
TI  - Long-Term Stability and Reliability of Black Phosphorus Field-Effect Transistors.
AB  - Black phosphorus has been recently suggested as a very promising material for the
      use in 2D field-effect transistors. However, due to its poor stability under
      ambient conditions, this material has not yet received as much attention as for
      instance MoS2. We show that the recently demonstrated Al2O3 encapsulation leads
      to highly stable devices. In particular, we report our long-term study on highly
      stable black phosphorus field-effect transistors which show stable device
      characteristics for at least eight months. This high stability allows us to
      perform a detailed analysis of their reliability with respect to hysteresis as
      well as the arguably most important reliability issue in Silicon technologies,
      the bias-temperature instability. We find that the hysteresis in these
      transistors depends strongly on the sweep rate and temperature. Moreover, the
      hysteresis dynamics in our devices are reproducible over a long time, which
      underlines their high reliability. Also, by using detailed physical models for
      oxide traps developed for Si technologies, we are able to capture the channel
      electrostatics of the black phosphorus FETs and determine the position of the
      defect energy band. Finally, we demonstrate that both hysteresis and bias
      temperature instabilities are due to thermally activated charge
      trapping/detrapping by oxide traps and can be reduced if the device is covered by
      Teflon-AF.

PMID- 27704780
TI  - Nanoparticle-Based Magnetoelectric BaTiO3-CoFe2O4 Thin Film Heterostructures for
      Voltage Control of Magnetism.
AB  - Multiferroic composite materials combining ferroelectric and ferromagnetic order
      at room temperature have great potential for emerging applications such as four
      state memories, magnetoelectric sensors, and microwave devices. In this paper, we
      report an effective and facile liquid phase deposition route to create
      multiferroic composite thin films involving the spin-coating of nanoparticle
      dispersions of BaTiO3, a well-known ferroelectric, and CoFe2O4, a highly
      magnetostrictive material. This approach offers great flexibility in terms of
      accessible film configurations (co-dispersed as well as layered films),
      thicknesses (from 100 nm to several MUm) and composition (5-50 wt % CoFe2O4 with
      respect to BaTiO3) to address various potential applications. A detailed
      structural characterization proves that BaTiO3 and CoFe2O4 remain phase-separated
      with clear interfaces on the nanoscale after heat treatment, while electrical and
      magnetic studies indicate the simultaneous presence of both ferroelectric and
      ferromagnetic order. Furthermore, coupling between these orders within the films
      is demonstrated with voltage control of the magnetism at ambient temperatures.

PMID- 27704781
TI  - Microscale Measurement and Visualization of Sulfide delta34S Using Photographic
      Film Sulfide Capture Coupled with Laser Ablation Multicollector Inductively
      Coupled Plasma Mass Spectrometry.
AB  - Measurements of the isotopic composition of sulfate and sulfide have been
      essential to uncovering the microbial and geochemical processes that drive
      Earth's sulfur cycle. These processes routinely operate over submillimeter
      spatial scales in anaerobic environments, necessitating sulfur isotopic
      measurement techniques that can identify isotopic variability over equivalently
      small scales. Here we present a new method for small-scale (102 MUm) measurements
      of delta34S using black and white photographic film sulfide capture coupled with
      delta34S determination using laser ablation multicollector inductively coupled
      plasma mass spectrometry. We find that the method enables measurement of delta34S
      for aqueous sulfide in natural waters at high spatial resolution (<1 mm2) with
      reasonable accuracy (<0.90/00, 2sigma) and external precision (<0.80/00, 2sigma),
      and across an environmentally relevant concentration range (0.01-20 mmol L-1). A
      concentration-dependent correction is required during data analysis to achieve
      these specifications, which corrects delta34S measurements for mixing with sulfur
      native to the film material and fractionation due to Ag2S precipitation from
      aqueous sulfide. We demonstrate the applicability of our technique using an
      anaerobic incubation of seawater and sediment, mapping two-dimensional
      delta34Ssulfide at a 535 MUm * 535 MUm spatial scale, with internal precisions of
      1.40/00 to 1.50/00. Our method offers the benefits of minimal sample preparation
      and common availability of sampling material (black and white photographic film),
      while retaining the necessary precision to identify sulfide delta34S variability
      and isotopic fractionations at high ambient sulfate and with high spatial
      resolutions in sulfidic environments.

PMID- 27704783
TI  - Single-Atom Switches and Single-Atom Gaps Using Stretched Metal Nanowires.
AB  - Utilizing individual atoms or molecules as functional units in electronic
      circuits meets the increasing technical demands for the miniaturization of
      traditional semiconductor devices. To be of technological interest, these
      functional devices should be high-yield, consume low amounts of energy, and
      operate at room temperature. In this study, we developed nanodevice called
      quantized conductance atomic switches (QCAS) that satisfies these requirements.
      The QCAS operates by applying a feedback-controlled voltage to a nano
      constriction within a stretched nanowire. We demonstrated that individual metal
      atoms could be removed from the nano-constriction and that the removed metal
      atoms could be refilled into the nano-constriction, thus yielding a reversible
      quantized conductance switch. We determined the key parameters for the QCAS
      between the 'on' and 'off' states at room temperature under a small operating
      voltage. By controlling the applied bias voltage, the atoms can be further
      completely removed from the constriction to break the nanowire, generating single
      atom nanogaps. These atomic nanogaps are quite stable under a sweeping voltage
      and can be re-adjusted with sub-angstrom accuracy, thus fulfilling the
      requirement of both reliability and flexibility for the high-yield fabrication of
      molecular devices.

PMID- 27704784
TI  - Novel Catalyst System for Suzuki-Miyaura Coupling of Challenging DNA-Linked Aryl
      Chlorides.
AB  - A novel Pd catalyst system, [(t-Bu)2P(OH)]2PdCl2 (POPd) with the ligand sodium 2'
      (dicyclohexylphosphino)-2,6-dimethoxy-[1,1'-biphenyl]-3-sulfonate, is reported.
      It effectively catalyzes the Suzuki-Miyaura coupling of challenging phenyl
      chlorides and pyrimidinyl chlorides that are covalently linked to a double
      stranded DNA-template with various boronic acids/esters.

PMID- 27704785
TI  - No d Orbitals but Walsh Diagrams and Maybe Banana Bonds: Chemical Bonding in
      Phosphines, Phosphine Oxides, and Phosphonium Ylides.

PMID- 27704786
TI  - New Insights into the Au(I)...Pb(II) Closed-Shell Interaction: Tuning of the
      Emissive Properties with the Intermetallic Distance.
AB  - Reaction of [Au2Ag2R4(Et2O)2] (R = C6Cl2F3- or C6F5-) with [Pb{HB(pz)3}]Cl in a
      1:2 molar ratio led to complexes [AuPb{HB(pz)3}R2] (R = C6Cl2F3- (2) or C6F5-
      (3)) through transmetalation reactions. The crystal structures of these complexes
      display unsupported Au(I)...Pb(II) interactions of 3.0954(4) (2) and 3.2778(4)
      (3) A, together with one (2) or two (3) F...Pb weak contacts. These intermetallic
      distances are compared to the shortest one found for the previously reported
      complex [Pb{HB(pz)3}Au(C6Cl5)2] (1) of 3.0494(4) (1) A, showing a clear
      dependence with the donating properties of the different aurate units. The
      complexes are emissive in the solid state due to charge transfer transitions
      associated with the presence of Au(I)...Pb(II) interactions, in which the
      intermetallic distance plays a crucial role. Density functional theory and time
      dependent density functional theory calculations support the assignment of the
      luminescent properties of the complexes. Ab initio Hartree-Fock and MP2
      calculations on model systems of complexes 2 and 3 show the presence of strong
      Au(I)...Pb(II) closed-shell interactions of an ionic plus dispersive nature
      together with weak F...Pb contacts of a dispersive origin in the case of
      complexes 2 and 3.

PMID- 27704782
TI  - Essential but Not Vulnerable: Indazole Sulfonamides Targeting Inosine
      Monophosphate Dehydrogenase as Potential Leads against Mycobacterium
      tuberculosis.
AB  - A potent, noncytotoxic indazole sulfonamide was identified by high-throughput
      screening of >100,000 synthetic compounds for activity against Mycobacterium
      tuberculosis (Mtb). This noncytotoxic compound did not directly inhibit cell wall
      biogenesis but triggered a slow lysis of Mtb cells as measured by release of
      intracellular green fluorescent protein (GFP). Isolation of resistant mutants
      followed by whole-genome sequencing showed an unusual gene amplification of a 40
      gene region spanning from Rv3371 to Rv3411c and in one case a potential promoter
      mutation upstream of guaB2 (Rv3411c) encoding inosine monophosphate dehydrogenase
      (IMPDH). Subsequent biochemical validation confirmed direct inhibition of IMPDH
      by an uncompetitive mode of inhibition, and growth inhibition could be rescued by
      supplementation with guanine, a bypass mechanism for the IMPDH pathway. Beads
      containing immobilized indazole sulfonamides specifically interacted with IMPDH
      in cell lysates. X-ray crystallography of the IMPDH-IMP-inhibitor complex
      revealed that the primary interactions of these compounds with IMPDH were direct
      pi-pi interactions with the IMP substrate. Advanced lead compounds in this series
      with acceptable pharmacokinetic properties failed to show efficacy in acute or
      chronic murine models of tuberculosis (TB). Time-kill experiments in vitro
      suggest that sustained exposure to drug concentrations above the minimum
      inhibitory concentration (MIC) for 24 h were required for a cidal effect, levels
      that have been difficult to achieve in vivo. Direct measurement of guanine levels
      in resected lung tissue from tuberculosis-infected animals and patients revealed
      0.5-2 mM concentrations in caseum and normal lung tissue. The high lesional
      levels of guanine and the slow lytic, growth-rate-dependent effect of IMPDH
      inhibition pose challenges to developing drugs against this target for use in
      treating TB.

PMID- 27704787
TI  - Recent Development of Carbon Nanotube Transparent Conductive Films.
AB  - Transparent conducting films (TCFs) are a critical component in many personal
      electronic devices. Transparent and conductive doped metal oxides are widely used
      in industry due to their excellent optoelectronic properties as well as the
      mature understanding of their production and handling. However, they are not
      compatible with future flexible electronics developments where large-scale
      production will likely involve roll-to-roll manufacturing. Recent studies have
      shown that carbon nanotubes provide unique chemical, physical, and optoelectronic
      properties, making them an important alternative to doped metal oxides. This
      Review provides a comprehensive analysis of carbon nanotube transparent
      conductive films covering detailed fabrication methods including patterning of
      the films, chemical doping effects, and hybridization with other materials. There
      is a focus on optoelectronic properties of the films and potential in
      applications such as photovoltaics, touch panels, liquid crystal displays, and
      organic light-emitting diodes in conjunction with a critical analysis of both the
      merits and shortcomings of carbon nanotube transparent conductive films.

PMID- 27704788
TI  - Sticky Situation: An Investigation of Robust Aqueous-Based Recombinant Spider
      Silk Protein Coatings and Adhesives.
AB  - The mechanical properties and biocompatibility of spider silks have made them one
      of the most sought after and studied natural biomaterials. A biomimetic process
      has been developed that uses water to solvate purified recombinant spider silk
      proteins (rSSps) prior to material formation. The absence of harsh organic
      solvents increases cost effectiveness, safety, and decreases the environmental
      impact of these materials. This development allows for the investigation of
      aqueous-based rSSps as coatings and adhesives and their potential applications.
      In these studies it was determined that fiber-based rSSps in nonfiber formations
      have the capability to coat and adhere numerous substrates, whether rough,
      smooth, hydrophobic, or hydrophilic. Further, these materials can be
      functionalized for a variety of processes. Drug-eluting coatings have been made
      with the capacity to release a variety of compounds in addition to their inherent
      ability to prevent blood clotting and biofouling. Additionally, spider silk
      protein adhesives are strong enough to outperform some conventional glues and
      still display favorable tissue implantation properties. The physical properties,
      corresponding capabilities, and potential applications of these nonfibrous
      materials were characterized in this study. Mechanical properties, ease of
      manufacturing, biodegradability, biocompatibility, and functionality are the
      hallmarks of these revolutionary spider silk protein materials.

PMID- 27704789
TI  - Graphene Coatings as Barrier Layers to Prevent the Water-Induced Corrosion of
      Silicate Glass.
AB  - Corrosion-protective coatings for silicate glass based on the transfer of one or
      two layers of graphene grown on copper by chemical vapor deposition have been
      demonstrated. The effectiveness of graphene to act as a glass corrosion inhibitor
      was evaluated by water immersion testing. After 120 days of immersion in water,
      bare glass samples had a significant increase in surface roughness and defects,
      which resulted in a marked reduction in fracture strength. In contrast, the
      single- and double-layer graphene-coated glasses experienced negligible changes
      in both fracture strength and surface roughness. The anticorrosion mechanism was
      also studied.

PMID- 27704790
TI  - Chlorination of 1-Carba-closo-dodecaborate and 1-Ammonio-closo-dodecaborate
      Anions.
AB  - Fully chlorinated carborate and dodecaborate cages such as [CHB11Cl11]- and
      [Me3NB12Cl11]- are prominent examples of valuable and chemically rather inert
      weakly coordinating anions. While both anions can be obtained by chlorination of
      the precursors [CH12B11]- and [H3NB12H11]- with SO2Cl2 followed by methylation
      for the synthesis of [Me3NB12Cl11]-, best results were found using photochemical
      chlorination with SO2Cl2 for [CH12B11]- and thermal chlorination with SO2Cl2 for
      [H3NB12H11]-. The hexachlorinated anion [n-Pr3NB12H5Cl6]- was formed readily
      within 30 min by chlorination of [n-Pr3NB12H11]-, but attempts to synthesize
      isopropyl-substituted ammonio-dodecaborates with a higher chlorination number
      resulted in the formation of mixtures and partial decomposition. The silver and
      trityl salts of the anions [CHB11Cl11]-, [Me3NB12Cl11]-, and [n-Pr3NB12H5Cl6]- as
      well as the contact ion-pair [Et2Al][Me3NB12Cl11] were also prepared, and the
      compounds [Ag(NCMe)][Me3NB12Cl11], [Et2Al][Me3NB12Cl11], and [Et4N][i
      Pr3NB12H5Cl6] were also characterized by X-ray crystallography.

PMID- 27704792
TI  - An Ultrastable Europium(III)-Organic Framework with the Capacity of
      Discriminating Fe2+/Fe3+ Ions in Various Solutions.
AB  - An ultrastable luminescent europium-organic framework, {[Eu(L)(H2O)2].NMP.H2O}n
      (CTGU-2; NMP = N-methyl-2-pyrrolidone), can first detect Fe2+/Fe3+ cations in
      different medium systems with high selectivity and sensitivity, and it also
      exhibits high sensitivity for Cr2O72- anion and acetone with a wide linear range
      and a low detection limit.

PMID- 27704791
TI  - Herbivory by an Outbreaking Moth Increases Emissions of Biogenic Volatiles and
      Leads to Enhanced Secondary Organic Aerosol Formation Capacity.
AB  - In addition to climate warming, greater herbivore pressure is anticipated to
      enhance the emissions of climate-relevant biogenic volatile organic compounds
      (VOCs) from boreal and subarctic forests and promote the formation of secondary
      aerosols (SOA) in the atmosphere. We evaluated the effects of Epirrita autumnata,
      an outbreaking geometrid moth, feeding and larval density on herbivore-induced
      VOC emissions from mountain birch in laboratory experiments and assessed the
      impact of these emissions on SOA formation via ozonolysis in chamber experiments.
      The results show that herbivore-induced VOC emissions were strongly dependent on
      larval density. Compared to controls without larval feeding, clear new particle
      formation by nucleation in the reaction chamber was observed, and the SOA mass
      loadings in the insect-infested samples were significantly higher (up to 150
      fold). To our knowledge, this study provides the first controlled documentation
      of SOA formation from direct VOC emission of deciduous trees damaged by known
      defoliating herbivores and suggests that chewing damage on mountain birch foliage
      could significantly increase reactive VOC emissions that can importantly
      contribute to SOA formation in subarctic forests. Additional feeding experiments
      on related silver birch confirmed the SOA results. Thus, herbivory-driven
      volatiles are likely to play a major role in future biosphere-vegetation
      feedbacks such as sun-screening under daily 24 h sunshine in the subarctic.

PMID- 27704793
TI  - Influence of Dissolved Silicate on Rates of Fe(II) Oxidation.
AB  - Increasing concentrations of dissolved silicate progressively retard Fe(II)
      oxidation kinetics in the circum-neutral pH range 6.0-7.0. As Si:Fe molar ratios
      increase from 0 to 2, the primary Fe(III) oxidation product transitions from
      lepidocrocite to a ferrihydrite/silica-ferrihydrite composite. Empirical results,
      supported by chemical kinetic modeling, indicated that the decreased
      heterogeneous oxidation rate was not due to differences in absolute Fe(II)
      sorption between the two solids types or competition for adsorption sites in the
      presence of silicate. Rather, competitive desorption experiments suggest Fe(II)
      was associated with more weakly bound, outer-sphere complexes on silica
      ferrihydrite compared to lepidocrocite. A reduction in extent of inner-sphere
      Fe(II) complexation on silica-ferrihydrite confers a decreased ability for Fe(II)
      to undergo surface-induced hydrolysis via electronic configuration alterations,
      thereby inhibiting the heterogeneous Fe(II) oxidation mechanism. Water samples
      from a legacy radioactive waste site (Little Forest, Australia) were shown to
      exhibit a similar pattern of Fe(II) oxidation retardation derived from elevated
      silicate concentrations. These findings have important implications for
      contaminant migration at this site as well as a variety of other groundwater/high
      silicate containing natural and engineered sites that might undergo iron redox
      fluctuations.

PMID- 27704794
TI  - Influence of Ligand Architecture in Tuning Reaction Bifurcation Pathways for
      Chlorite Oxidation by Non-Heme Iron Complexes.
AB  - Reaction bifurcation processes are often encountered in the oxidation of
      substrates by enzymes and generally lead to a mixture of products. One particular
      bifurcation process that is common in biology relates to electron transfer versus
      oxygen atom transfer by high-valent iron(IV)-oxo complexes, which nature uses for
      the oxidation of metabolites and drugs. In biomimicry and bioremediation, an
      important reaction relates to the detoxification of ClOx- in water, which can
      lead to a mixture of products through bifurcated reactions. Herein we report the
      first three water-soluble non-heme iron(II) complexes that can generate chlorine
      dioxide from chlorite at ambient temperature and physiological pH. These
      complexes are highly active oxygenation oxidants and convert ClO2- into either
      ClO2 or ClO3- via high-valent iron(IV)-oxo intermediates. We characterize the
      short-lived iron(IV)-oxo species and establish rate constants for the bifurcation
      mechanism leading to ClO2 and ClO3- products. We show that the ligand
      architecture of the metal center plays a dominant role by lowering the reduction
      potential of the metal center. Our experiments are supported by computational
      modeling, and a predictive valence bond model highlights the various factors
      relating to the substrate and oxidant that determine the bifurcation pathway and
      explains the origins of the product distributions. Our combined kinetic,
      spectroscopic, and computational studies reveal the key components necessary for
      the future development of efficient chlorite oxidation catalysts.

PMID- 27704795
TI  - The Nature of the Bridging Anion Controls the Single-Molecule Magnetic Properties
      of DyX4M 12-Metallacrown-4 Complexes.
AB  - A family of DyX4M(12-MCMnIII(N)shi-4) compounds were synthesized and magnetically
      characterized (X = salicylate, acetate, benzoate, trimethylacetate, M = NaI or
      KI). The bridging ligands were systematically varied while keeping the remainder
      of the MC-geometry constant. The type of monovalent cation, necessary for charge
      balance, was also altered. The dc magnetization and susceptibility of all
      compounds were similar across the series. Regardless of the identity of the
      countercation, the Dy(Hsal)4M 12-MC-4 compounds were the only compounds to show
      frequency-dependent ac magnetic susceptibility, a hallmark of single-molecule
      magnetism. This indicates that the nature of the bridging ligand in the 12
      MCMnIII(N)shi-4 compounds strongly affects the out-of-phase magnetic properties.
      The SMM behavior appears to correlate with the pKa of the bridging ligand.

PMID- 27704796
TI  - Whole-Organism Transcriptomic Analysis Provides Mechanistic Insight into the
      Acute Toxicity of Emamectin Benzoate in Daphnia magna.
AB  - Emamectin benzoate (EMB) is an antisea lice chemical widely used in the
      aquaculture that may also unintentionally affect nontarget crustaceans in the
      environment. Although the adverse effects of this compound are well documented in
      various species, the full modes of action (MoAs) are still not well
      characterized. The current study was therefore conducted to characterize the MoAs
      of EMB and link perturbations of key toxicological pathways to adverse effects in
      the model freshwater crustacean Daphnia magna. Effects on molting and survival
      were determined after 48 h exposure to EMB, whereas global transcriptional
      changes and the ecdysone receptor (EcR) binding potency was determined to
      characterize the MoA. The results showed that the molting frequency and survival
      of D. magna decreased in a concentration-dependent manner, and the observed
      changes could not be attributed to direct interactions with the EcR. Major MoAs
      such as activation of glutamate-gated chloride channels and gamma-aminobutyric
      acid signaling, disruption of neuroendocrine regulation of molting, perturbation
      of energy homeostasis, suppression of DNA repair and induction of programmed cell
      death were observed by transcriptional analysis and successfully linked to the
      adverse effects. This study has demonstrated that acute exposure to intermediate
      and high pM levels of EMB may pose hazards to nontarget crustaceans in the
      aquatic environment.

PMID- 27704797
TI  - Phosphorus(V) Porphyrin-Based Molecular Turnstiles.
AB  - A new cationic molecular turnstile based on a P(V) porphyrin backbone bearing two
      pyridyl interaction sites, one at the meso position of the porphyrin and the
      other on the handle connected to the porphyrin through P-O bonds, was designed
      and synthesized. The dynamic behavior of the turnstile 2, investigated by 1D and
      2D 1H NMR techniques, showed that in the absence of an effector, the turnstile is
      in its open state and undergoes a free rotation of the rotor (the handle) around
      the stator (the porphyrin backbone). In the presence of an external effector such
      as Ag+ cation or H+, the turnstile is switched to its closed states 2-Ag+ and 2
      H+, respectively. The locking/unlocking process is reversible and may be achieved
      by precipitation of AgBr upon addition of Et4NBr in the case of the silver-locked
      turnstile or by addition of Et3N in the case of the proton-locked turnstile.

PMID- 27704798
TI  - The Mn4Ca-cluster of the photosynthetic oxygen evolving centre: its structure,
      function and evolution.
AB  - Photosystem II is the chlorophyll containing enzyme in which the very first
      chemical energy storing reaction of photosynthesis occurs. It does so by
      splitting water into molecular oxygen and hydrogen equivalents at a catalytic
      centre composed of four Mn ions and one Ca2+. All the oxygen in the atmosphere is
      derived from this reaction and without it the biosphere, as we know it, would not
      exist. Indeed its appearance about 3 billion years ago gave rise to the "big bang
      of evolution". Thus understanding the structure and functioning of this metal
      cluster is a major topic in science and here I discuss it in terms of research
      over of the last twelve years dating back to when it was first proposed to be a
      Mn3CaO4 cubane with the fourth Mn attached to cubane by one of its oxo bridging
      bonds. In so doing a number of novel properties emerge for this metallo-protein
      with implications for its mechanism and evolutionary origin.

PMID- 27704800
TI  - Synthesis, Structure, and Antibacterial Activity of a Thallium(III)-Containing
      Polyoxometalate, [Tl2{B-beta-SiW8O30(OH)}2]12.
AB  - We have synthesized and structurally characterized the first discrete thallium
      containing polyoxometalate, [Tl2{B-beta-SiW8O30(OH)}2]12- (1). Polyanion 1 was
      characterized in the solid-state and shown to be solution-stable by 203/205Tl
      NMR, electrospray ionization mass spectrometry, and electrochemical studies. The
      antibacterial activity of 1 was also investigated.

PMID- 27704799
TI  - Post Gold King Mine Spill Investigation of Metal Stability in Water and Sediments
      of the Animas River Watershed.
AB  - We applied spectroscopy, microscopy, diffraction, and aqueous chemistry methods
      to investigate the persistence of metals in water and sediments from the Animas
      River 13 days after the Gold King Mine spill (August 5, 2015). The Upper Animas
      River watershed, located in San Juan Colorado, is heavily mineralized and
      impacted by acid mine drainage, with low pH water and elevated metal
      concentrations in sediments (108.4 +/- 1.8 mg kg-1 Pb, 32.4 +/- 0.5 mg kg-1 Cu,
      729.6 +/- 5.7 mg kg-1 Zn, and 51 314.6 +/- 295.4 mg kg-1 Fe). Phosphate and
      nitrogen species were detected in water and sediment samples from Farmington, New
      Mexico, an intensive agricultural area downstream from the Animas River, while
      metal concentrations were low compared to those observed upstream. Solid-phase
      analyses of sediments suggest that Pb, Cu, and Zn are associated with metal
      bearing jarosite and other minerals (e.g., clays, Fe-(oxy)hydroxides). The
      solubility of jarosite at near-neutral pH and biogeochemical processes occurring
      downstream could affect the stability of metal-bearing minerals in river
      sediments. This study contributes relevant information about the association of
      metal mixtures in a heavy mineralized semiarid region, providing a foundation to
      better understand long-term metal release in a public and agricultural water
      supply.

PMID- 27704801
TI  - Complex Microstructure and Magnetism in Polymorphic CaFeSeO.
AB  - The structural complexity of the antiferromagnetic oxide selenide CaFeSeO is
      described. The compound contains puckered FeSeO layers composed of FeSe2O2
      tetrahedra sharing all their vertexes. Two polymorphs coexist that can be derived
      from an archetype BaZnSO structure by cooperative tilting of the FeSe2O2
      tetrahedra. The polymorphs differ in the relative arrangement of the puckered
      layers of vertex-linked FeSe2O2 tetrahedra. In a noncentrosymmetric Cmc21
      polymorph (a = 3.89684(2) A, b = 13.22054(8) A, c = 5.93625(2) A) the layers are
      related by the C-centering translation, while in a centrosymmetric Pmcn
      polymorph, with a similar cell metric (a = 3.89557(6) A, b = 13.2237(6) A, c =
      5.9363(3) A), the layers are related by inversion. The compound shows long-range
      antiferromagnetic order below a Neel temperature of 159(1) K with both polymorphs
      showing antiferromagnetic coupling via Fe-O-Fe linkages and ferromagnetic
      coupling via Fe-Se-Fe linkages within the FeSeO layers. The magnetic
      susceptibility also shows evidence for weak ferromagnetism which is modeled in
      the refinements of the magnetic structure as arising from an uncompensated spin
      canting in the noncentrosymmetric polymorph. There is also a spin glass component
      to the magnetism which likely arises from the disordered regions of the structure
      evident in the transmission electron microscopy.

PMID- 27704802
TI  - Molecular Characterization of Brown Carbon in Biomass Burning Aerosol Particles.
AB  - Emissions from biomass burning are a significant source of brown carbon (BrC) in
      the atmosphere. In this study, we investigate the molecular composition of
      freshly emitted biomass burning organic aerosol (BBOA) samples collected during
      test burns of sawgrass, peat, ponderosa pine, and black spruce. We demonstrate
      that both the BrC absorption and the chemical composition of light-absorbing
      compounds depend significantly on the type of biomass fuels. Common BrC
      chromophores in the selected BBOA samples include nitro-aromatics, polycyclic
      aromatic hydrocarbon derivatives, and polyphenols spanning a wide range of
      molecular weights, structures, and light absorption properties. A number of
      biofuel-specific BrC chromophores are observed, indicating that some of them may
      be used as source-specific markers of BrC. On average, ~50% of the light
      absorption in the solvent-extractable fraction of BBOA can be attributed to a
      limited number of strong BrC chromophores. The absorption coefficients of BBOA
      are affected by solar photolysis. Specifically, under typical atmospheric
      conditions, the 300 nm absorbance decays with a half-life of ~16 h. A "molecular
      corridor" analysis of the BBOA volatility distribution suggests that many BrC
      compounds in the fresh BBOA have low saturation mass concentration (<1 MUg m-3)
      and will be retained in the particle phase under atmospherically relevant
      conditions.

PMID- 27704803
TI  - Thermodynamic, Kinetic, Structural, and Computational Studies of the Ph3Sn-H,
      Ph3Sn-SnPh3, and Ph3Sn-Cr(CO)3C5Me5 Bond Dissociation Enthalpies.
AB  - The kinetics of the reaction of Ph3SnH with excess *Cr(CO)3C5Me5 = *Cr, producing
      HCr and Ph3Sn-Cr, was studied in toluene solution under 2-3 atm CO pressure in
      the temperature range of 17-43.5  degrees C. It was found to obey the rate
      equation d[Ph3Sn-Cr]/dt = k[Ph3SnH][*Cr] and exhibit a normal kinetic isotope
      effect (kH/kD = 1.12 +/- 0.04). Variable-temperature studies yielded DeltaH? =
      15.7 +/- 1.5 kcal/mol and DeltaS? = -11 +/- 5 cal/(mol.K) for the reaction. These
      data are interpreted in terms of a two-step mechanism involving a
      thermodynamically uphill hydrogen atom transfer (HAT) producing Ph3Sn* and HCr,
      followed by rapid trapping of Ph3Sn* by excess *Cr to produce Ph3Sn-Cr. Assuming
      an overbarrier of 2 +/- 1 kcal/mol in the HAT step leads to a derived value of
      76.0 +/- 3.0 kcal/mol for the Ph3Sn-H bond dissociation enthalpy (BDE) in toluene
      solution. The reaction enthalpy of Ph3SnH with excess *Cr was measured by
      reaction calorimetry in toluene solution, and a value of the Sn-Cr BDE in Ph3Sn
      Cr of 50.4 +/- 3.5 kcal/mol was derived. Qualitative studies of the reactions of
      other R3SnH compounds with *Cr are described for R = nBu, tBu, and Cy. The
      dehydrogenation reaction of 2Ph3SnH -> H2 + Ph3SnSnPh3 was found to be rapid and
      quantitative in the presence of catalytic amounts of the complex Pd(IPr)(P(p
      tolyl)3). The thermochemistry of this process was also studied in toluene
      solution using varying amounts of the Pd(0) catalyst. The value of DeltaH = -15.8
      +/- 2.2 kcal/mol yields a value of the Sn-Sn BDE in Ph3SnSnPh3 of 63.8 +/- 3.7
      kcal/mol. Computational studies of the Sn-H, Sn-Sn, and Sn-Cr BDEs are in good
      agreement with experimental data and provide additional insight into factors
      controlling reactivity in these systems. The structures of Ph3Sn-Cr and Cy3Sn-Cr
      were determined by X-ray crystallography and are reported. Mechanistic aspects of
      oxidative addition reactions in this system are discussed.

PMID- 27704804
TI  - Synthesis of 13(R)-Hydroxy-7Z,10Z,13R,14E,16Z,19Z Docosapentaenoic Acid (13R
      HDPA) and Its Biosynthetic Conversion to the 13-Series Resolvins.
AB  - Specialized pro-resolving lipid mediators are biosynthesized during the
      resolution phase of acute inflammation from n-3 polyunsaturated fatty acids.
      Recently, the isolation and identification of the four novel mediators denoted 13
      series resolvins, namely, RvT1 (1), RvT2 (2), RvT3 (3) and RvT4 (4), were
      reported, which showed potent bioactions characteristic for specialized pro
      resolving lipid mediators. Herein, based on results from LC/MS-MS
      metabololipidomics and the stereoselective synthesis of 13(R)-hydroxy
      7Z,10Z,13R,14E,16Z,19Z docosapentaenoic acid (13R-HDPA, 5), we provide direct
      evidence that the four novel mediators 1-4 are all biosynthesized from the
      pivotal intermediate 5. The UV and LC/MS-MS results from synthetic 13R-HDPA (5)
      matched those from endogenously and biosynthetically produced material obtained
      from in vivo infectious exudates, endothelial cells, and human recombinant COX-2
      enzyme. Stereochemically pure 5 was obtained with the use of a chiral pool
      starting material that installed the configuration at the C-13 atom as R. Two
      stereoselective Z-Wittig reactions and two Z-selective reductions of internal
      alkynes afforded the geometrically pure alkene moieties in 5. Incubation of 5
      with isolated human neutrophils gave all four RvTs. The results presented herein
      provide new knowledge on the biosynthetic pathways and the enzymatic origin of
      RvTs 1-4.

PMID- 27704805
TI  - Highly Efficient Cascade Reaction for Selective Formation of Spirocyclobutenes
      from Dienallenes via Palladium-Catalyzed Oxidative Double Carbocyclization
      Carbonylation-Alkynylation.
AB  - A highly selective cascade reaction that allows the direct transformation of
      dienallenes to spirocyclobutenes (spiro[3.4]octenes) as single isomers has been
      developed. The reaction involves formation of overall four C-C bonds and proceeds
      via a palladium-catalyzed oxidative transformation with insertion of olefin,
      olefin, and carbon monoxide. Under slightly different reaction conditions an
      additional CO insertion takes place to give spiro[4.4]nonenes with formation of
      overall five C-C bonds.

PMID- 27704806
TI  - Eutrophication Increases Phytoplankton Methylmercury Concentrations in a Coastal
      Sea-A Baltic Sea Case Study.
AB  - Eutrophication is expanding worldwide, but its implication for production and
      bioaccumulation of neurotoxic monomethylmercury (MeHg) is unknown. We developed a
      mercury (Hg) biogeochemical model for the Baltic Sea and used it to investigate
      the impact of eutrophication on phytoplankton MeHg concentrations. For model
      evaluation, we measured total methylated Hg (MeHgT) in the Baltic Sea and found
      low concentrations (39 +/- 16 fM) above the halocline and high concentrations in
      anoxic waters (1249 +/- 369 fM). To close the Baltic Sea MeHgT budget, we
      inferred an average normoxic water column HgII methylation rate constant of 2 *
      10-4 d-1. We used the model to compare Baltic Sea's present-day (2005-2014)
      eutrophic state to an oligo/mesotrophic scenario. Eutrophication increases
      primary production and export of organic matter and associated Hg to the sediment
      effectively removing Hg from the active biogeochemical cycle; this results in a
      27% lower present-day water column Hg reservoir. However, increase in organic
      matter production and remineralization stimulates microbial Hg methylation
      resulting in a seasonal increase in both water and phytoplankton MeHg reservoirs
      above the halocline. Previous studies of systems dominated by external MeHg
      sources or benthic production found eutrophication to decrease MeHg levels in
      plankton. This Baltic Sea study shows that in systems with MeHg production in the
      normoxic water column eutrophication can increase phytoplankton MeHg content.

PMID- 27704809
TI  - Regulation of DNA Strand Displacement Using Allosteric DNA Toehold.
AB  - Toehold-mediated DNA strand displacement is the fundamental basis for the
      construction and operation of diverse DNA devices, including circuits, machines,
      sensors, and reconfigurable structures. Controllable activation and regulation of
      toeholds are critical to construct devices with multistep, autonomous, and
      complex behaviors. A handful of unique toehold activation mechanisms, including
      toehold-exchange, associative toehold, and remote toehold, have been developed
      and are often combined to achieve desired strand displacement behaviors and
      functions. Here we report an allosteric DNA toehold (A-toehold) design that
      allows the flexible regulation of DNA strand displacement by splitting an input
      strand into an A-toehold and branch migration domain. Because of its simplicity,
      the A-toehold mechanism can be a useful addition to the current toolbox of DNA
      strand displacement techniques. We demonstrated that A-toehold enabled a number
      of interesting functions that were previously shown using more sophisticated DNA
      strand displacement systems, including 1) continuously tuning the rate of strand
      displacement, 2) dynamic control of strand displacement reactions, and 3)
      selective activation of multiple strand displacement reactions. Moreover, by
      combining A-toehold and toehold-exchange mechanisms, we have successfully
      constructed a non-covalent DNA catalysis network that resembles an allosteric
      enzyme.

PMID- 27704807
TI  - Rearranged 6/6/5/6-Fused Triterpenoid Acids from the Stems of Kadsura coccinea.
AB  - Fourteen new rearranged 6/6/5/6-fused triterpenoid acids, namely, kadcoccine
      acids A-N (1-14), were isolated from an EtOAc-soluble extract of the stems of
      Kadsura coccinea. Their structures were characterized mainly by analyzing 1D and
      2D NMR and HRESIMS data and were shown to feature a rare 14(13->12)-abeo
      lanostane skeleton. Compounds 7 and 8 represented the first examples of a 5
      substituted 2(5H)-furanone motif on the C-17 side chain of this skeleton. The
      absolute configurations of C-23 for compounds 1, 7, and 8 were determined by
      comparison of their experimental electronic circular dichroism spectra. All the
      isolates were screened for their in vitro cytotoxicity against six human tumor
      cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW-480, and HeLa), and compounds 2
      and 8 exhibited weak inhibitory effects with IC50 values ranging from 3.11 to
      7.77 MUM.

PMID- 27704808
TI  - Bissubvilides A and B, Cembrane-Capnosane Heterodimers from the Soft Coral
      Sarcophyton subviride.
AB  - Two new biscembranoid-like compounds, bissubvilides A (1) and B (2), were
      isolated together with sarsolilide B (3), the proposed biogenetic precursor to 1,
      from the soft coral Sarcophyton subviride. The structures and absolute
      configurations were solved by spectroscopic analysis and TDDFT/ECD and DFT/NMR
      calculations. The bissubvilides represent a novel biscembranoid-like skeleton
      presumed to derive from a cembrane-type diene and a capnosane-type dienophile via
      a Diels-Alder reaction. These two molecules exerted no cytotoxicity against MG-63
      or A549 tumor cells or HuH7 tumor stem cells.

PMID- 27704810
TI  - Mechanism-Guided Development of a Highly Active Bis-Thiourea Catalyst for Anion
      Abstraction Catalysis.
AB  - We describe the rational design of a linked, bis-thiourea catalyst with enhanced
      activity relative to monomeric analogs in a representative enantioselective anion
      abstraction reaction. Mechanistic insights guide develop-ment of this linking
      strategy to favor substrate activation though the intramolecular cooperation of
      two thiourea sub-units while avoiding nonproductive aggregation. The resulting
      catalyst platform overcomes many of the practical limitations that have plagued
      hydrogen-bond donor catalysis and enables use of catalyst loadings as low as 0.05
      mol %. Computational analyses of possible anion-binding modes provide detailed
      insight into the precise mechanism of anion-abstraction catalysis with this
      pseudo-dimeric thiourea.

PMID- 27704812
TI  - Effective Fully Polarizable QM/MM Approach To Model Vibrational Circular
      Dichroism Spectra of Systems in Aqueous Solution.
AB  - We propose a methodology, based on the combination of classical Molecular
      Dynamics (MD) simulations with a fully polarizable Quantum Mechanical
      (QM)/Molecular Mechanics (MM)/Polarizable Continuum Model (PCM) Hamiltonian, to
      calculate Vibrational Circular Dichroism (VCD) spectra of chiral systems in
      aqueous solution. Polarization effects are included in the MM force field by
      exploiting an approach based on Fluctuating Charges (FQ). By performing the MD,
      the description of the solvating environment is enriched by taking into account
      the dynamical aspects of the solute-solvent interactions. On the other hand, the
      QM/FQ/PCM calculation of the VCD spectrum ensures an accurate description of the
      electronic density of the solute and a proper account for the specific
      interactions in solution. The application of our approach to (R)-methyloxirane
      and (l)-alanine in aqueous solution gives calculated spectra in remarkable
      agreement with their experimental counterparts and a substantial improvement with
      respect to the same spectra calculated with the PCM.

PMID- 27704811
TI  - Vobasinyl-Iboga Alkaloids from Tabernaemontana elegans: Cell Cycle Arrest and
      Apoptosis-Inducing Activity in HCT116 Colon Cancer Cells.
AB  - Phytochemical investigation of the roots of the African medicinal plant
      Tabernaemontana elegans led to the isolation of three new (1-3) and two known (4
      and 5) bisindole alkaloids of the vobasinyl-iboga type. The structures of 1-3
      were assigned by spectroscopic methods, mainly using 1D and 2D NMR experiments.
      All of the isolated compounds were evaluated for their cytotoxicity against
      HCT116 colon and HepG2 liver carcinoma cells by the MTS metabolism assay.
      Compounds 1-3 and 5 were found to be cytotoxic to HCT116 colon cancer cells,
      displaying IC50 values in the range 8.4 to >10 MUM. However, the compounds did
      not display significant cytotoxicity against HepG2 cancer cells. The cytotoxicity
      of compounds 1-3 and 5 was corroborated using a lactate dehydrogenase assay.
      Hoechst staining and nuclear morphology assessment and caspase-3/7 activity
      assays were also performed for investigating the activity of compounds 1-3 and 5
      as apoptosis inducers. The induced inhibition of proliferation of HCT116 cells by
      compounds 1 and 2 was associated with G1 phase arrest, while compounds 3 and 5
      induced G2/M cell cycle arrest. These results showed that the new vobasinyl-iboga
      alkaloids 1-3 and compound 5 are strong inducers of apoptosis and cell cycle
      arrest in HCT116 colon cancer cells.

PMID- 27704813
TI  - Arborinane Triterpenoids from Rubia philippinensis Inhibit Proliferation and
      Migration of Vascular Smooth Muscle Cells Induced by the Platelet-Derived Growth
      Factor.
AB  - The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs)
      are associated with cardiovascular diseases and related complications. Such
      deleterious proliferation and migration events are triggered by cytokines and
      growth factors, and among them, platelet-derived growth factor (PDGF) is
      recognized as the most potent inducer. Despite the genus Rubia being researched
      to identify valuable commercial and medicinal virtues, Rubia philippinensis has
      rarely been investigated. Nine arborinane-type triterpenoids (1-9) were
      identified from this underutilized plant species. In particular, 4 was identified
      as the first arborinane derivative carrying a ketocarbonyl motif at C-19. The
      presence of the cyclopentanone moiety and the associated configurational
      assignment were determined by utilizing NOE and coupling constant analysis. These
      compounds were assessed for their inhibitory potential on PDGF-induced
      proliferation and the migration of VSMCs. Treatment with 5 MUM compound 5 (62.6
      +/- 10.7%) and compound 9 (41.1 +/- 4.7%) impeded PDGF-stimulated proliferation
      without exerting cytotoxicity. Compound 7 exhibited antimigration activity in a
      dose-dependent manner (38.5 +/- 3.0% at 10 MUM, 57.6 +/- 3.2% at 30 MUM). These
      results suggest that the arborinane-type triterpenoids may be a pertinent
      starting point for the development of cardiovascular drugs capable of preventing
      the intimal accumulation of VSMCs.

PMID- 27704814
TI  - Epimeric Face-Selective Oxidations and Diastereodivergent Transannular Oxonium
      Ion Formation Fragmentations: Computational Modeling and Total Syntheses of 12
      Epoxyobtusallene IV, 12-Epoxyobtusallene II, Obtusallene X, Marilzabicycloallene
      C, and Marilzabicycloallene D.
AB  - The total syntheses of 12-epoxyobtusallene IV, 12-epoxyobtusallene II,
      obtusallene X, marilzabicycloallene C, and marilzabicycloallene D as halogenated
      C15-acetogenin 12-membered bicyclic and tricyclic ether bromoallene-containing
      marine metabolites from Laurencia species are described. Two enantiomerically
      pure C4-epimeric dioxabicyclo[8.2.1]tridecenes were synthesized by E-selective
      ring-closing metathesis where their absolute stereochemistry was previously set
      via catalytic asymmetric homoallylic epoxidation and elaborated via
      regioselective epoxide-ring opening and diastereoselective bromoetherification.
      Epimeric face-selective oxidation of their Delta12,13 olefins followed by
      bromoallene installation allowed access to the oppositely configured 12,13
      epoxides of 12-epoxyobtusallene II and 12-epoxyobtusallene IV. Subsequent
      exploration of their putative biomimetic oxonium ion formation-fragmentations
      reactions revealed diastereodivergent pathways giving marilzabicycloallene C and
      obtusallene X, respectively. The original configurations of the substrates
      evidently control oxonium ion formation and their subsequent preferred mode of
      fragmentation by nucleophilic attack at C9 or C12. Quantum modeling of this
      stereoselectivity at the omegaB97X-D/Def2-TZVPPD/SCRF = methanol level revealed
      that in addition to direction resulting from hydrogen bonding, the dipole moment
      of the ion-pair transition state is an important factor. Marilzabicycloallene D
      as a pentahalogenated 12-membered bicyclic ether bromoallene was synthesized by a
      face-selective chloronium ion initiated oxonium ion formation-fragmentation
      process followed by subsequent bromoallene installation.

PMID- 27704816
TI  - Rapid, Large-Area Synthesis of Hierarchical Nanoporous Silica Hybrid Films on
      Flexible Substrates.
AB  - We report a simple strategy for the creation of large-area nanoporous hybrid
      films of silica, carbon, and gold on polyethylene terephthalate via photothermal
      processing. This method enables the selective heating of light-absorbing thin
      films on low-temperature substrates using submillisecond light pulses generated
      by a xenon flash lamp. The film contains gold nanoparticles as the nano-heaters
      to convert light energy into heat, a sacrificial block copolymer surfactant to
      generate mesopores, and cross-linked polyhedral oligomeric silsesquioxane (POSS)
      as the silica source to form the skeleton of the porous structure. Hierarchical
      porous structures are achieved in the films after photothermal treatment with
      uniform mesopores (44~48 nm) on the surface and interconnected macropores (>50
      nm) underneath resulting from a foaming effect during release gaseous
      decomposition products. The loading of gold nanoparticles is up to 43 wt % in the
      product with less than 2 wt % organic residue. This rapid and large-area
      synthetic process of porous structures is compatible with roll-to-roll
      manufacturing for the fabrication of flexible devices.

PMID- 27704815
TI  - Drug Affinity Responsive Target Stability (DARTS) Identifies Laurifolioside as a
      New Clathrin Heavy Chain Modulator.
AB  - Five new diterpenes (1-5) and a megastigmane derivative (6) were isolated from
      the aerial parts of Euphorbia laurifolia, along with several known compounds.
      Their structures were elucidated by NMR, MS, and ECD and by chemical methods. A
      chemical proteomics drug affinity responsive target stability (DARTS) approach to
      investigate the lathyrane diterpene 1, laurifolioside, on its putative cellular
      target(s) was performed. Clathrin heavy chain 1, a protein mainly involved in
      selective uptake of proteins, viruses, and other macromolecules at the plasma
      membrane of cells, was identified as the major interaction partner of compound 1.
      The modulation of clathrin activity by 1 was studied through microscopy,
      molecular docking, and molecular dynamics studies, suggesting a new activity of
      lathyrane diterpenes in the modulation of trafficking pathways.

PMID- 27704817
TI  - Oxytetracycline Toxicity and its Effect on Phytoremediation by Sedum
      Plumbizincicola and Medicago Sativa in Metal Contaminated Soil.
AB  - Excessive use of antibiotics potentially threatens human health, agricultural
      production and soil phytoremediation. This arouses concern over the potential
      adverse effects of a commonly used antibiotic, oxytetracycline (OTC), on plants
      used for soil remediation and possible stimulation of antibiotic resistance genes
      in soils. A greenhouse experiment was conducted to investigate different rates
      (0, 1, 5, and 25 mg kg-1) and frequencies (one single high and daily low
      application) of OTC addition to soil on phytoremediation of a heavy metal
      contaminated soil by Sedum plumbizincicola and/or Medicago sativa (alfalfa).
      After 90 days both Cd and Zn were substantially removed by phytoextraction into
      S. plumbizincicola shoots especially at the high OTC (25 mg kg-1) treatment which
      also led to inhibition of anti-oxidative enzyme activities in both plant species.
      Soil microbial activity decreased significantly with the addition of OTC and this
      was ameliorated by planting alfalfa and S. plumbizincicola together. OTC at < 5
      mg kg-1 increased the biomass of both plant species but the frequency of OTC
      addition had no effect on the rate of metal removal. Alfalfa exhibited greater
      detoxification ability and effectiveness in soil microbial activity promotion
      than S. plumbizincicola with intercropping. Phytoremediation by alfalfa and S.
      plumbizincicola in association can both promote the removal of heavy metals and
      also alleviate the toxic effects of pollutants to plants and soil microbes even
      at relatively high soil OTC concentrations.

PMID- 27704818
TI  - Palladium-Catalyzed Intramolecular Fujiwara-Hydroarylation: Synthesis of
      Benzo[a]phenazines Derivatives.
AB  - An atom-economical Pd-catalyzed approach for the synthesis of benzophenazine
      derivatives using substituted 2-aryl-3-(aryl/alkylethynyl) quinoxaline in the
      presence of trifluoroacetic acid at 65  degrees C has been described. The
      chemistry involves in situ generation of cationic Pd(II) species, which
      functionalized the aromatic C-H bonds via electrophilic metalation followed by
      concomitant intramolecular trans-insertion of C-C triple bond to aryl-Pd complex.
      The results were supported by various control experiments including with electron
      deficient arenes and deuterium labeling studies. The deuterium labeling studies
      supports electrophilic palladation of aromatic C-H over activation of C-C triple
      bond of alkyne. The structure of synthesized compounds was further confirmed by X
      ray crystallography studies. This catalytic protocol has been efficiently applied
      for novel synthesis of highly functionalized benzo fused phenazines.

PMID- 27704819
TI  - Photocatalytic Reduction of Low Concentration of CO2.
AB  - A novel molecular photocatalytic system with not only high reduction ability of
      CO2 but also high capture ability of CO2 has been developed using a Ru(II)-Re(I)
      dinuclear complex as a photocatalyst. By using this photocatalytic system, CO2 of
      10% concentration could be selectively converted to CO with almost same
      photocatalysis to that under a pure CO2 atmosphere (TONCO > 1000, PhiCO > 0.4).
      Even 0.5% concentration of CO2 was reduced with 60% initial efficiency of CO
      formation by using the same system compared to that using pure CO2 (TONCO > 200).
      The Re(I) catalyst unit in the photocatalyst can efficiently capture CO2, which
      proceeds CO2 insertion to the Re-O bond, and then reduce the captured CO2 by
      using an electron supplied from the photochemically reduced Ru photosensitizer
      unit.

PMID- 27704820
TI  - The Synthesis and Characterization of Highly Fluorescent Polycyclic Azaborine
      Chromophores.
AB  - Six new heteroaromatic polycyclic azaborine chromophores were designed,
      synthesized, and investigated as easily tunable high-luminescent organic
      materials. The impact of the nitrogen-boron-hydroxy (N-BOH) unit in the
      azaborines was investigated by comparison with their N-carbonyl analogs.
      Insertion of the N-B(OH)-C unit into heteroaromatic polycyclic compounds resulted
      in strong visible absorption and sharp fluorescence with efficient quantum
      yields. The solid-state fluorescence of the heteroaromatic polycyclic compounds
      displayed a large Stokes shift compared to being in solution. The large Stokes
      shifts observed offset the self-quench effect in the solid state.

PMID- 27704821
TI  - Discovery and Development of the Anti-Human Immunodeficiency Virus Drug,
      Emtricitabine (Emtriva, FTC).
AB  - The HIV/AIDS epidemic, which was first reported on in 1981, progressed in just 10
      years to a disease afflicting 10 million people worldwide including 1 million in
      the US. In 1987, AZT was approved for treating HIV/AIDS. Unfortunately, its
      clinical usefullness was severly limited by associated toxicities and the
      emergence of resistance. Three other drugs that were approved in the early 1990s
      suffered from similar liabilities. In 1990, the Liotta group at Emory University
      developed a highly diastereoselective synthesis of racemic 3'-thia-2',3'
      dideoxycytidine and 3'-thia-2',3'-5-fluorodideoxycytidine and demonstrated that
      these compounds exhibited excellent anti-HIV activity with no apparent
      cytotoxicity. Subsequently, the enantiomers of these compounds were separated
      using enzyme-mediated kinetic resolutions and their (-)-enantiomers (3TC and FTC,
      respectively) were found to have exceptionally attractive preclinical profiles.
      In addition to their anti-HIV activity, 3TC and FTC potently inhibit the
      replication of hepatitis B virus. The development of FTC, which was being carried
      out by Burroughs Wellcome, had many remarkable starts and stops. For example,
      passage studies indicated that the compound rapidly selected for a single
      resistant mutant, M184V, and that this strain was 500-1000-fold less sensitive to
      FTC than was wild-type virus. Fortunately, it was found that combinations of AZT
      with either 3TC or FTC were synergistic. The effectiveness of AZT-3TC combination
      therapy was subsequently demonstrated in four independent clinical trials, and in
      1997, the FDA approved Combivir, a fixed dose combination of AZT and 3TC. In
      phase 1 clinical trials, FTC was well tolerated by all subjects with no adverse
      events observed. However, the development of FTC was halted by the aquistition of
      Wellcome PLC by Glaxo PLC in January 1995. In 1996, Triangle Pharmaceuticals
      licensed FTC from Emory and initiated a series of phase I/II clinical studies
      that demonstrated the safety and efficacy of the drug. In August 1998, FTC was
      granted "Fast Track" status, based primarily on its potential for once daily
      dosing. While the outcomes of two subsequent phase III trials were positive, a
      third phase III clinical trial involving combinations of 3TC or FTC with
      stavudine and neviripine had to be terminated due to serious liver-related
      adverse events. Although analysis of the data suggested that the liver toxicity
      was due to neviripine, the FDA decided that the study could not be used for drug
      registration. Ultimately, in January 2003, Gilead Sciences acquired Triangle
      Pharmaceuticals and completed the development of FTC (emtricitabine), which was
      approved for once a day, oral administration in July 2003. A year later, Truvada,
      a once a day, oral, fixed dose combination of emtricitabine and tenofovir
      disoproxyl fumarate received FDA approval and quickly became the accepted first
      line therapy when used with a third antiretroviral agent. In July 2006, the FDA
      approved Atripla, a once a day, oral, fixed dose combination of emtricitabine,
      tenofovir disoproxyl fumarate, and efavirenz, which represented the culmination
      of two decades of research that had transformed AIDS from a death sentence to a
      manageable chronic disease.

PMID- 27704822
TI  - Structural Characterization and Assessment of the Cytotoxicity of 2,3-Dihydro-1H
      indene Derivatives and Coumarin Glucosides from the Bark of Streblus indicus.
AB  - A pair of enantiomers and a pair of 2,3-dihydro-1H-indene epimers, rac-indidene A
      (rac-1), indidenes B and C (2, 3); four new coumarin glucosides (4-7); and four
      known coumarin glucosides (8-11) were isolated from the bark of Streblus indicus
      (Bur.) Corner. The structures of 1-11 were defined by physical data analyses,
      including MS, NMR, and single-crystal X-ray diffraction. The absolute
      configurations of the 2,3-dihydro-1H-indene derivatives were defined via
      experimental and calculated ECD data. rac-Indidene A and indidenes B and C showed
      inhibitory activity against A549 and MCF-7 tumor cells with IC50 values in the
      range of 2.2 +/- 0.1 to 7.2 +/- 0.9 MUM.

PMID- 27704823
TI  - Ab initio Molecular Dynamics Study of H2 Formation inside POSS Compounds. 2. The
      Effect of an Encapsulated Hydrogen Molecule.
AB  - The mechanism and dynamics for the formation of a hydrogen molecule in the cavity
      of POSS (polyhedral oligomeric silsesquioxane) compounds have been investigated
      by ab initio molecular orbital and ab initio molecular dynamics (AIMD) methods.
      The host molecules are two POSS compounds, T8 ([HSiO1.5]8) (Oh) and T12
      ([HSiO1.5]12) (D2d). To investigate the H2 formation reaction, two approaches
      were considered: trajectories were initiated by inserting a second hydrogen atom
      into (I) a hydrogen molecule encapsulated-POSS (H + H2@Tn -> (H + H2)@Tn; n = 8,
      12), and (II) the hydrogen atom and hydrogen molecule-encapsulated-POSS (H + (H +
      H2)@Tn -> 2 H2@Tn; n = 8 and 12). A wide variety of reactions were observed
      depending on the system and the initial conditions, especially in process II.
      Therefore, for reaction II, an energy decomposition analysis was employed to
      examine the variation of the distribution of the translational, rotational and
      vibrational kinetic energies of the guest species along the reaction processes,
      and to determine the role of each energy component for the H2 formation. This
      analysis provides important insights into the expected kinetic energy
      distributions among the products of encapsulation reactions.

PMID- 27704824
TI  - Long-Range Reactivity Modulations in Geranyl Chloride Derivatives.
AB  - Derivatives of geraniol are versatile synthetic intermediates that are useful for
      synthesizing a variety of terpenoid natural products; however, the results
      presented herein show that subtle differences in the structures of functionalized
      geranyl chlorides can significantly impact their abilities to function as
      effective electrophiles in synthetic reactions. A series of focused kinetics
      experiments identify specific structure-activity relationships that illustrate
      the importance not only of steric bulk, but also of electronic effects from
      distant regions of the molecules that contribute to their overall levels of
      reactivity. Computational modeling suggests that destabilization of the reactant
      by filled-filled orbital mixing events in some, but not all, conformations may be
      a critical contributor to these important electronic effects.

PMID- 27704825
TI  - Ejection of Metal Particles into Superfluid 4He by Laser Ablation.
AB  - The dynamics following laser ablation of a metal target immersed in superfluid
      $^4$He is studied by time-resolved shadowgraph photography. The delayed ejection
      of hot micrometer-sized particles from the target surface into the liquid was
      indirectly observed by monitoring the formation and growth of gaseous bubbles
      around the particles. The experimentally determined particle average velocity
      distribution appears similar as previously measured in vacuum but exhibits a
      sharp cutoff at the speed of sound of the liquid. The propagation of the subsonic
      particles terminates in slightly elongated non-spherical gas bubbles residing
      near the target whereas faster particles reveal an unusual hydrodynamic response
      of the liquid. Based on the previously established semi-empirical model developed
      for macroscopic objects, the ejected transonic particles exhibit supercavitating
      flow to reduce their hydrodynamic drag. Supersonic particles appear to follow a
      completely different propagation mechanism as they leave discrete and semi
      continuous bubble trails in the liquid. The relatively low number density of the
      observed non-spherical gas bubbles indicates that only large micron-sized
      particles are visualized in the experiments. Although the unique properties of
      superfluid helium allow a detailed characterization of these processes, the
      developed technique can be used to study the hydrodynamic response of any liquid
      to fast propagating objects on the micrometer-scale.

PMID- 27704826
TI  - Controllable Self-Assembly of Amphiphilic Dendrimers at Silica Surface: Effect of
      Molecular Topological Structure and Salinity.
AB  - The adsorption kinetics and equilibrium of amphiphilic dendrimers based on
      poly(amidoamine) PAMAM modified with dodecyl chain GnQPAMC12(n represents the
      generation number) with different generation at silica-water interface have been
      investigated. The effect of molecular shape with different charge characteristics
      on the adsorption kinetics, adsorption isotherms and the conformation of self
      assembled layer has been elucidated. For the adsorption kinetics, two steps were
      observed including the adsorption of individual molecules at the concentrations
      below cmc and the predominant adsorption of aggregates above cmc. However, the
      adsorption isotherm, with the generation number as a function, presented
      exceptional characteristic, in which, a decrease of adsorption mass with
      different levels occurred in high generation of amphiphilicdendrimers, depending
      on the balance of hydrophobic interaction and electrostatic repulsion. Atomic
      force microscopy imaging showed that flatten films with pores (spacing) of
      various shapes and roughness of 3 ~ 4 nm were formed, of which the pores
      (spacing) decreased obviously as the generation increases. The addition of
      electrolyte (NaBr) has great effect on the film morphology formed by G3QPAMC12
      dendrimer adsorbed at silica-water interface, showing that the film became closer
      with smaller pores with increased NaBr concentration.

PMID- 27704828
TI  - Anion Binding of One-, Two-, and Three-Armed Thiourea Receptors Examined via
      Photoelectron Spectroscopy and Quantum Computations.
AB  - A benzene ring substituted with 1-3 thiourea containing arms (1-3) were examined
      by photoelectron spectroscopy and density functional theory computations. Their
      conjugate bases and chloride, acetate and dihydrogen phosphate anion clusters are
      reported. The resulting vertical and adiabatic detachment energies span from 3.93
      - 5.82 eV (VDE) and 3.65 - 5.10 (ADE) for the deprotonated species and 4.88 -
      5.97 eV (VDE) and 4.45 - 5.60 eV (ADE) for the anion complexes. These results
      reveal the stabilizing effects of multiple hydrogen bonds and anionic host-guest
      interactions in the gas phase. Previously measured equilibrium binding constants
      in aqueous dimethyl sulfoxide for all three thioureas are compared to the present
      results and cooperative binding is uniformly observed in the gas phase but only
      for one case (i.e., 3 * H2PO4-) in solution.

PMID- 27704829
TI  - A Stereoselective Route to Tetrahydrobenzoxazepines and Tetrahydrobenzodiazepines
      via Ring-Opening and Aza-Michael Addition of Activated Aziridines with 2
      Hydroxyphenyl and 2-Aminophenyl Acrylates.
AB  - A simple and efficient synthetic route to 2,3,4,5-tetrahydrobenzoxazepines and 
      benzodiazepines bearing easily functionalizable appendages has been developed by
      ring-opening of activated aziridines with 2-hydroxyphenyl acrylates and 2
      aminophenyl acrylate, respectively, and subsequent intramolecular C-N bond
      formation through palladium-catalyzed aza-Michael reaction. The straightforward
      synthetic approach delivers the desired molecular scaffolds in high yields (up to
      82%) with excellent stereoselectivity (ee up to 94%).

PMID- 27704827
TI  - How Large Should the QM Region Be in QM/MM Calculations? The Case of Catechol O
      Methyltransferase.
AB  - Hybrid quantum mechanical-molecular mechanical (QM/MM) simulations are widely
      used in studies of enzymatic catalysis. Until recently, it has been cost
      prohibitive to determine the asymptotic limit of key energetic and structural
      properties with respect to increasingly large QM regions. Leveraging recent
      advances in electronic structure efficiency and accuracy, we investigate
      catalytic properties in catechol O-methyltransferase, a prototypical
      methyltransferase critical to human health. Using QM regions ranging in size from
      reactants-only (64 atoms) to nearly one-third of the entire protein (940 atoms),
      we show that properties such as the activation energy approach within chemical
      accuracy of the large-QM asymptotic limits rather slowly, requiring approximately
      500-600 atoms if the QM residues are chosen simply by distance from the
      substrate. This slow approach to asymptotic limit is due to charge transfer from
      protein residues to the reacting substrates. Our large QM/MM calculations enable
      identification of charge separation for fragments in the transition state as a
      key component of enzymatic methyl transfer rate enhancement. We introduce charge
      shift analysis that reveals the minimum number of protein residues (approximately
      11-16 residues or 200-300 atoms for COMT) needed for quantitative agreement with
      large-QM simulations. The identified residues are not those that would be
      typically selected using criteria such as chemical intuition or proximity. These
      results provide a recipe for a more careful determination of QM region sizes in
      future QM/MM studies of enzymes.

PMID- 27704830
TI  - Diastereoselective Mannich Reactions Using Fluorinated Ketones: Synthesis of
      Stereogenic Carbon-Fluorine Units.
AB  - A diastereoselective Mannich reaction of simple alpha-fluoro ketones with N-tert
      butylsulfinylimines was developed. This method provides a concise route to a
      variety of structurally diverse alpha-fluoro-beta-amino ketones containing
      fluorinated stereogenic carbon centers; good yields and high
      diastereoselectivities were achieved. This method uses readily accessible
      starting materials and has a broad substrate scope: cyclic and linear alpha
      fluoro ketones and fluoromethyl ketones are all suitable substrates.

PMID- 27704831
TI  - Pd-Catalyzed Aminocarbonylation of the Blaise Reaction Intermediate: One-Pot
      Synthesis of (Z)-3-Methyleneisoindolin-1-ones from Nitriles.
AB  - A highly efficient method for the one-pot synthesis of stereocontrolled (Z)-3
      methyleneisoindolin-1-ones was developed starting from 2-bromoarylnitriles via
      tandem sequential reaction with a Reformatsky reagent (Blaise reaction), followed
      by Pd-catalyzed intramolecular aminocarbonylation with carbon monoxide at 1 atm
      pressure. It has been found that the conformational flexibility of the
      bisphophine ligand is of great importance to the success of this tandem
      aminocarbonylation reaction.

PMID- 27704832
TI  - Reaction of N2O and CO Catalyzed with Small Copper Clusters: Mechanism and
      Design.
AB  - Highly active catalytic clusters are observed during the reaction mechanism study
      of the copper cluster Cux (x = 4-15) catalyzed N2O + CO -> N2 + CO2 reaction. It
      was shown that N2O adsorbs on the copper cluster without an activation barrier
      and the nitrogen-oxygen bond is broken during the next step. The analysis of the
      chemical bonding showed that the oxide ion formation is an important driving
      force of the reaction. Among the different clusters Cu12 was the most active as
      the nitrogen-oxygen bond is cleaved without an energy barrier, while the nitrogen
      molecule is eliminated. It was shown that the resulting copper oxide cluster is
      reduced easily with carbon-monoxide. The elimination of the thus formed carbon
      dioxide is thermodynamically a highly favored process, even at low temperature.
      Thus, Cu12 cluster is a potentially highly active catalyst at ambient condition
      for the N2O + CO -> N2 + CO2 reaction.

PMID- 27704833
TI  - Vibronic Coupling in the X2Pig-A2Piu Band System of Diacetylene Radical Cation.
AB  - Vibronic interactions in the two energetically lowest electronic states (X2Pig
      A2Piu) of the diacetylene radical cation (C4H2*+) are theoretically examined
      here. The spectroscopy of these two electronic states of C4H2*+ has been a
      subject of considerable interest and measured in the laboratory by various
      groups. Inspired by numerous experimental data, we attempt here a detailed
      investigation of vibronic interactions within and between the doubly degenerate
      Pi electronic states and their impact on the vibronic structure of each state. A
      vibronic coupling model is constructed in a diabatic electronic basis and with
      the aid of ab initio quantum chemistry calculations. The vibronic structures of
      the electronic states are calculated by time-independent and time-dependent
      quantum mechanical methods. The progression of vibrational modes in the vibronic
      band is identified, assigned, and compared with the literature data. The
      nonradiative internal conversion dynamics is also examined and discussed.

PMID- 27704834
TI  - Theoretical Study of the Catalytic Hydrogenation of Alkenes by a
      Disilaferracyclic Complex: Can the Fe-Si sigma-Bond-Assisted Activation of H-H
      Bonds Allow Development of a Catalysis of Iron?
AB  - The mechanisms associated with the hydrogenation of alkenes catalyzed by the iron
      complex Fe(cis-CO)2{o-(SiMe2)2C6H4}2(H)2 (1) were investigated by DFT
      calculations. The complex 1 has a structure in which the iron center is bonded to
      four silicon atoms and two hydrides. Secondary Si...H...Si interactions were also
      observed. The exchange of a 1,2-bis(dimethylsilyl)benzene ligand with ethylene
      and hydrogen gives a disilaferracycle bearing eta2-(CH2?CH2) and eta2-H2 ligands.
      The catalytic cycle initiated from the disilaferracycle involves cleavage of a H
      H linkage assisted by an Fe-Si bond to form Fe-H and eta1-(H-Si) moieties (step
      1), hydrogen migration from the Fe-H group to the eta2-(CH2?CH2) ligand which
      accomplishes the insertion of ethylene into the Fe-H bond (step 2), and reaction
      of the resulting beta-agostic ethyl moiety with the eta2-(H-Si) group to form
      ethane on the iron atom (step 3). The octahedral geometry of 1 as well as the
      presence of pi-acidic CO ligands and Fe-Si sigma-bonds contributes to all of the
      catalytic intermediates and the transition states being in the low-spin state.
      Steps 1 and 3 correspond to the sigma-complex-assisted metathesis (sigma-CAM)
      mechanisms proposed by Perutz and Sabo-Etienne, suggesting that these mechanisms
      can assist in the design of iron-based hydrogenation catalysts operating under
      mild conditions.

PMID- 27704835
TI  - Electroreductive Intermolecular Coupling of Coumarins with Benzophenones:
      Synthesis of 4-(2-Hydroxyphenyl)-5,5-diaryl-gamma-butyrolactones, 2-(2,2-Diaryl
      2,3-dihydrobenzofuran-3-yl)acetic Acids, and 4-(Diarylmethyl)coumarins.
AB  - The electroreductive coupling of coumarins with benzophenones in the presence of
      TMSCl gave adducts reacted at the 4-position of coumarins as trimethylsilyl
      ethers. From 3-methylcoumarin, 3,4-cis-adducts were formed stereoselectively. The
      de-trimethylsilylation of the adducts with 1 M HCl aq or TBAF in THF at 25 
      degrees C produced 4-(2-hydroxyphenyl)-5,5-diaryl-gamma-butyrolactones. The gamma
      butyrolactones were further transformed to 2-(2,2-diaryl-2,3-dihydrobenzofuran-3
      yl)acetic acids by treatment with 1 M HCl aq at reflux temperature. The de
      trimethylsilylation of the adducts with 1 M HCl in MeOH afforded 2-(2,2-diaryl
      2,3-dihydrobenzofuran-3-yl)acetic acid methyl esters. The de
      trimethylsiloxylation of the adducts or dehydration of the gamma-butyrolactones
      brought about 4-(diarylmethyl)coumarins.

PMID- 27704836
TI  - Near-Edge X-ray Absorption Fine Structure Investigation of the Quasi-One
      Dimensional Organic Conductor (TMTSF)2PF6.
AB  - We present high-resolution near-edge X-ray absorption fine structure (NEXAFS)
      measurements at the P L2/3 edges, F K edge, C K edge, and Se M2/3 edges of the
      quasi-one-dimensional (1D) conductor and superconductor (TMTSF)2PF6. NEXAFS
      allows probing the donor and acceptor moieties separately; spectra were recorded
      between room temperature (RT) and 30 K at normal incidence. Spectra taken around
      RT were also studied as a function of the angle (theta) between the electric
      field of the X-ray beam and the 1D conducting direction. In contrast with a
      previous study of the S L2/3-edges spectra in (TMTTF)2AsF6, the Se M2/3 edges of
      (TMTSF)2PF6 do not exhibit a well-resolved spectrum. Surprisingly, the C K-edge
      spectra contain three well-defined peaks exhibiting strong and nontrivial theta
      and temperature dependence. The nature of these peaks as well as those of the F K
      edge spectra could be rationalized on the basis of first-principles DFT
      calculations. Despite the structural similarity, the NEXAFS spectra of
      (TMTSF)2PF6 and (TMTTF)2AsF6 exhibit important differences. In contrast with the
      case of (TMTTF)2AsF6, the F K-edge spectra of (TMTSF)2PF6 do not change with
      temperature despite stronger donor-anion interactions. All these features reveal
      subtle differences in the electronic structure of the TMTSF and TMTTF families of
      salts.

PMID- 27704837
TI  - AGEs/RAGE-Related Neurodegeneration: daf-16 as a Mediator, Insulin as an
      Ameliorant, and C. elegans as an Expedient Research Model.
AB  - Advanced glycation end-products (AGEs) are nonenzymatically glycated proteins,
      lipids, and nucleic acids. These compounds both originate exogenously and are
      formed endogenously, and they are associated, along with one of their receptors
      (RAGE), with a variety of pathologies and neurodegeneration. Some of their
      deleterious effects include affecting insulin signaling and FOXO-related pathways
      in both receptor-dependent and -independent manners. A potential ameliorating
      agent for these effects is insulin, which is being studied in several in vivo and
      in vitro models; one of these models is C. elegans, whose maintenance, genetic
      malleability, and well-described longevity-related pathways make it an optimal
      complementary model for assessing these objectives. In the realm of neuroscience,
      this model is currently being used only for general assessment of
      neurodegeneration and shortened lifespan. We suggest that characterization of (a)
      the effects of AGEs/RAGE on specific neurotransmitter systems, (b) the role of
      the daf-2/daf-16 pathway in these neurodegenerative processes, and

PMID- 27704839
TI  - That Little Extra Kick: Non-adiabatic Effects in Acetaldehyde Photodissociation.
AB  - The effect of non-adiabatic transitions on branching ratios, kinetic and internal
      energy distribution of fragments, and reaction mechanisms observed in acetadehyde
      photodissociation is investigated by non-adiabatic molecular dynamics (NAMD)
      simulations using time-dependent hybrid density functional theory and Tully
      surface hopping. Homolytic bond breaking is approximately captured by allowing
      spin symmetry to break. The NAMD simulations reveal that non-adiabatic
      transitions selectively enhance the kinetic energy of certain internal degrees of
      freedom within approximately 50 fs. Branching ratios from NAMD and conventional
      ''hot'' Born-Oppenheimer molecular dynamics (BOMD) are similar and qualitatively
      agree with experiment. However, as opposed to the BOMD simulations, NAMD captures
      the high-energy tail of the experimental kinetic energy distribution. The extra
      "kick'' of the nuclei in the direction of the non-adiabatic coupling vector
      results from non-adiabatic transitions close to conical intersections. From a
      mechanistic perspective, the non-adiabatic effects favor asynchronous over
      synchronous fragmentation and tend to suppress roaming.

PMID- 27704838
TI  - Analysis of Differential Efficacy and Affinity of GABAA (alpha1/alpha2) Selective
      Modulators.
AB  - Selective modulators of the gamma-amino butyric acid (GABAA) family of receptors
      have the potential to treat a range of disease states related to cognition, pain,
      and anxiety. While the development of various alpha subunit-selective modulators
      is currently underway for the treatment of anxiety disorders, a mechanistic
      understanding of the correlation between their bioactivity and efficacy, based on
      ligand-target interactions, is currently still lacking. In order to alleviate
      this situation, in the current study we have analyzed, using ligand- and
      structure-based methods, a data set of 5440 GABAA modulators. The Spearman
      correlation (rho) between binding activity and efficacy of compounds was
      calculated to be 0.008 and 0.31 against the alpha1 and alpha2 subunits of GABA
      receptor, respectively; in other words, the compounds had little diversity in
      structure and bioactivity, but they differed significantly in efficacy. Two
      compounds were selected as a case study for detailed interaction analysis due to
      the small difference in their structures and affinities (DeltapKi(comp1_alpha1 -
      comp2_alpha1) = 0.45 log units, DeltapKi(comp1_alpha2 - comp2_alpha2) = 0 log
      units) as compared to larger relative efficacies (DeltaRE(comp1_alpha1 -
      comp2_alpha1) = 1.03, DeltaRE(comp1_alpha2 - comp2_alpha2) = 0.21). Docking
      analysis suggested that His-101 is involved in a characteristic interaction of
      the alpha1 receptor with both compounds 1 and 2. Residues such as Phe-77, Thr
      142, Asn-60, and Arg-144 of the gamma chain of the alpha1gamma2 complex also
      showed interactions with heterocyclic rings of both compounds 1 and 2, but these
      interactions were disturbed in the case of alpha2gamma2 complex docking results.
      Binding pocket stability analysis based on molecular dynamics identified three
      substitutions in the loop C region of the alpha2 subunit, namely, G200E, I201T,
      and V202I, causing a reduction in the flexibility of alpha2 compared to alpha1.
      These amino acids in alpha2, as compared to alpha1, were also observed to
      decrease the vibrational and dihedral entropy and to increase the hydrogen bond
      content in alpha2 in the apo state. However, freezing of both alpha1 and alpha2
      was observed in the ligand-bound state, with an increased number of internal
      hydrogen bonds and increased entropy. Therefore, we hypothesize that the amino
      acid differences in the loop C region of alpha2 are responsible for
      conformational changes in the protein structure compared to alpha1, as well as
      for the binding modes of compounds and hence their functional signaling.

PMID- 27704842
TI  - Dense Hydrocarbon Structures at Megabar Pressures.
AB  - The structure, bonding, and other properties of phases in the carbon-hydrogen
      system over a range of conditions is of considerable importance to a broad range
      of scientific problems. However, the phase diagram of the C-H system at high
      pressures and temperatures is still not known. To search for new low energy
      hydrocarbon structures, we carried out a systematic structure prediction search
      for the C-H system from 100-300 GPa. We confirmed several previously predicted
      structures but found additional stoichiometries that adopt more stable
      structures. In particular, a C2H4 structure is found that has an indirect band
      gap and phonon calculations confirm it is dynamically stable over a broad
      pressure range. We also identify more carbon-rich structures that are
      energetically favorable. The results are important for understanding carbon
      hydrogen interactions in high-pressure astrophysical environments, the deep
      carbon cycle in planetary interiors, as well as resolving controversies for
      recent experiments on hydrogen-containing samples at megabar pressures using
      diamond anvil cells.

PMID- 27704841
TI  - Quest for Inexpensive Hydrogen Isotopic Fractionation: Do We Need 2D Quantum
      Confining in Porous Materials or Are Rough Surfaces Enough? The Case of Ammonia
      Nanoclusters.
AB  - We study the adsorption energetics and quantum properties of the molecular
      hydrogen isotopes H2, D2, and T2 onto the surface of rigid ammonia nanoclusters
      with quantum simulations and accurate model potential energy surfaces (PES). A
      highly efficient diffusion Monte Carlo (DMC) algorithm for rigid rotors allowed
      us to accurately define zero-point adsorption energies for the three isotopes, as
      well as the degree of translational and rotational delocalization that each
      affords on the surface. From the data emerges that the quantum adsorption energy
      (Eads) of T2 can be up to twice the one of H2 at 0 K, suggesting the possibility
      of exploiting some form of solid ammonia to selectivity separate hydrogen
      isotopes at low temperatures (?20 K). This is discussed by focusing on the
      structural motif that may be more effective for the task. The analysis of the
      contributions to Eads, however, surprisingly indicates that the average kinetic
      energy (Ekin) and rotation energy (Erotkin) of T2 can also be, respectively, 2
      times and 20 times higher than those of H2; this finding markedly deviates from
      what is predicted for hydrogen molecules inside carbon nanotubes (CNT) or
      metallic-organic frameworks (MOF), where Ekin and Erotkin is higher for H2 due to
      the unavoidable effects of confinement and hindrance to its rotational motion.
      The rationale for these differences is provided by the geometrical distributions
      for the rigid rotors, which reveal an increasingly stronger coupling between
      rotational and translational degrees of freedom upon increasing the isotopic
      mass. This effect has never been observed before on adsorbing surfaces (e.g.,
      graphite) and is induced by a strongly anisotropic and anharmonic bowl-like
      potential experienced by the rotors.

PMID- 27704840
TI  - Targeted Metabolic Profiling of the Tg197 Mouse Model Reveals Itaconic Acid as a
      Marker of Rheumatoid Arthritis.
AB  - Rheumatoid arthritis is a progressive, highly debilitating disease where early
      diagnosis, enabling rapid clinical intervention, would provide obvious benefits
      to patients, healthcare systems, and society. Novel biomarkers that enable
      noninvasive early diagnosis of the onset and progression of the disease provide
      one route to achieving this goal. Here a metabolic profiling method has been
      applied to investigate disease development in the Tg197 arthritis mouse model.
      Hind limb extract profiling demonstrated clear differences in metabolic
      phenotypes between control (wild type) and Tg197 transgenic mice and highlighted
      raised concentrations of itaconic acid as a potential marker of the disease.
      These changes in itaconic acid concentrations were moderated or indeed reversed
      when the Tg197 mice were treated with the anti-hTNF biologic infliximab (10 mg/kg
      twice weekly for 6 weeks). Further in vitro studies on synovial fibroblasts
      obtained from healthy wild-type, arthritic Tg197, and infliximab-treated Tg197
      transgenic mice confirmed the association of itaconic acid with rheumatoid
      arthritis and disease-moderating drug effects. Preliminary indications of the
      potential value of itaconic acid as a translational biomarker were obtained when
      studies on K4IM human fibroblasts treated with hTNF showed an increase in the
      concentrations of this metabolite.

PMID- 27704843
TI  - Observation of Electronic Excitation Transfer through Light Harvesting Complex II
      Using Two-dimensional Electronic-vibrational Spectroscopy.
AB  - Light Harvesting Complex II (LHCII) serves a central role in light harvesting for
      oxygenic photosynthesis, and is arguably the most important photosynthetic
      antenna complex. In this work, we present two-dimensional electronic-vibrational
      (2DEV) spectra of LHCII isolated from spinach, demonstrating the possibility of
      using this technique to track the transfer of electronic excitation energy
      between specific pigments within the complex. We assign the spectral bands via
      comparison with the 2DEV spectra of the isolated chromophores, chlorophyll a and
      b, and present evidence that excitation energy between the pigments of the
      complex are observed in these spectra. Finally, we analyze the essential
      components of the 2DEV spectra using singular value decomposition, which makes it
      possible to reveal the relaxation pathways within this complex.

PMID- 27704844
TI  - Predicting Band Gaps with Hybrid Density Functionals.
AB  - We compare the ability of four popular hybrid density functionals (B3LYP, B3PW91,
      HSE, and PBE0) for predicting band gaps of semiconductors and insulators over a
      large benchmark set using a consistent methodology. We observe no significant
      statistical difference in their overall performance although the screened hybrid
      HSE is more accurate for typical semiconductors. HSE can improve its accuracy for
      large large band gap materials --without affecting that of semiconductors-- by
      including a larger portion of Hartree--Fock exchange in its short range. Given
      that screened hybrids are computationally much less expensive than their global
      counterparts, we conclude that they are a better option for the black box
      prediction of band gaps.

PMID- 27704845
TI  - Reversible Shape and Plasmon Tuning in Hollow AgAu Nanorods.
AB  - The internal structure of hollow AgAu nanorods created by partial galvanic
      replacement was manipulated reversibly, and its effect on optical properties was
      mapped with nanometer resolution. Using the electron beam in a scanning
      transmission electron microscope to create solvated electrons and reactive
      radicals in an encapsulated solution-filled cavity in the nanorods, Ag ions were
      reduced nearby the electron beam, reshaping the core of the nanoparticles without
      affecting the external shape. The changes in plasmon-induced near-field
      properties were then mapped with electron energy-loss spectroscopy without
      disturbing the internal structure, and the results are supported by finite
      difference time-domain calculations. This reversible shape and near-field control
      in a hollow nanoparticle actuated by an external stimulus introduces
      possibilities for applications in reprogrammable sensors, responsive materials,
      and optical memory units. Moreover, the liquid-filled nanorod cavity offers new
      opportunities for in situ microscopy of chemical reactions.

PMID- 27704846
TI  - Pore Environment Effects on Catalytic Cyclohexane Oxidation in Expanded
      Fe2(dobdc) Analogues.
AB  - Metal-organic frameworks are a new class of heterogeneous catalysts in which
      molecular-level control over both the immediate and long-range chemical
      environment surrounding a catalytic center can be readily achieved. Here, the
      oxidation of cyclohexane to cyclohexanol and cyclohexanone is used as a model
      reaction to investigate the effect of a hydrophobic pore environment on product
      selectivity and catalyst stability in a series of iron-based frameworks.
      Specifically, expanded analogues of Fe2(dobdc) (dobdc4- = 2,5-dioxido-1,4
      benzenedicarboxylate) were synthesized and evaluated, including the biphenyl
      derivative Fe2(dobpdc) (H4dobpdc = 4,4'-dihydroxy-[1,1'-biphenyl]-3,3'
      dicarboxylic acid), the terphenyl derivative Fe2(dotpdc) (H4dotpdc = 4,4"
      dihydroxy-[1,1':4',1"-terphenyl]-3,3"-dicarboxylic acid), and three modified
      terphenyl derivatives in which the central ring is replaced with tetrafluoro-,
      tetramethyl-, or di-tert-butylaryl groups. Within these five materials, a
      remarkable 3-fold enhancement of the alcohol:ketone (A:K) ratio and an order of
      magnitude increase in turnover number are achieved by simply altering the
      framework pore diameter and installing nonpolar functional groups near the iron
      site. Mossbauer spectroscopy, kinetic isotope effect, and gas adsorption
      measurements reveal that variations in the A:K selectivities arise from
      differences in the cyclohexane adsorption enthalpies of these frameworks, which
      become more favorable as the number of hydrophobic residues and thus van der
      Waals interactions increase.

PMID- 27704847
TI  - Reconfigurable van der Waals Heterostructured Devices with Metal-Insulator
      Transition.
AB  - Atomically thin two-dimensional (2D) materials range from semimetallic graphene
      to insulating hexagonal boron nitride to semiconducting transition-metal
      dichalcogenides. Recently, metal-insulator-semiconductor field effect transistors
      built from these 2D elements were studied for flexible and transparent
      electronics. However, to induce ambipolar characteristics for alternative power
      efficient circuitry, ion-gel gating is often employed for high capacitive
      coupling, limiting stable operation at ambient conditions. Here, we report
      reconfigurable MoTe2 optoelectronic transistors with all 2D components, where the
      device can be reconfigured by both drain and gate voltages. Eight different
      configurations for each fixed voltage are spatially resolved by scanning
      photocurrent microscopy. In addition, metal-insulator transitions are observed in
      both electron and hole carriers under 2 V due to strong Coulomb interaction in
      the system. Furthermore, the vertical tunneling photocurrent through multiple van
      der Waals layers between the gate and source contacts is measured. Our
      reconfigurable devices offer potential building blocks for system-on-a-chip
      optoelectronics.

PMID- 27704848
TI  - Nontargeted LC-MS Metabolomics Approach for Metabolic Profiling of Plasma and
      Urine from Pigs Fed Branched Chain Amino Acids for Maximum Growth Performance.
AB  - The metabolic response in plasma and urine of pigs when feeding an optimum level
      of branched chain amino acids (BCAAs) for best growth performance is unknown. The
      objective of the current study was to identify the metabolic phenotype associated
      with the BCAAs intake level that could be linked to the animal growth
      performance. Three dose-response studies were carried out to collect blood and
      urine samples from pigs fed increasing levels of Ile, Val, or Leu followed by a
      nontargeted LC-MS approach to characterize the metabolic profile of biofluids
      when dietary BCAAs are optimum for animal growth. Results showed that
      concentrations of plasma hypoxanthine and tyrosine (Tyr) were higher while
      concentrations of glycocholic acid, tauroursodeoxycholic acid, and taurocholic
      acid were lower when the dietary Ile was optimum. Plasma 3-methyl-2-oxovaleric
      acid and creatine were lower when dietary Leu was optimum. The optimum dietary
      Leu resulted in increased urinary excretion of ascorbic acid and choline and
      relatively decreased excretion of 2-aminoadipic acid, acetyl-dl-valine, Ile, 2
      methylbutyrylglycine, and Tyr. In conclusion, plasma glycocholic acid and
      taurocholic acid were discriminating metabolites to the optimum dietary Ile. The
      optimum dietary Leu was associated with reduced plasma creatine and urinary 2
      aminoadipic acid and elevated urinary excretion of ascorbic acid and choline. The
      optimum dietary Val had a less pronounced metabolic response reflected in plasma
      or urine than other BCAA.

PMID- 27704849
TI  - Copper Coordination Features of Human Islet Amyloid Polypeptide: The Type 2
      Diabetes Peptide.
AB  - Human islet amyloid polypeptide (hIAPP) is the major component of amyloid
      deposits found in pancreatic beta-cells of patients with type 2 diabetes (T2D).
      Copper ions have an inhibitory effect on the amyloid aggregation of hIAPP, and
      they may play a role in the etiology of T2D. However, deeper knowledge of the
      structural details of the copper-hIAPP interaction is required to understand the
      molecular mechanisms involved. Here, we performed a spectroscopic study of Cu(II)
      binding to hIAPP and several variants, using electron paramagnetic resonance
      (EPR), nuclear magnetic resonance (NMR), electronic absorption, and circular
      dichroism (CD) in the UV-vis region in combination with Born-Oppenheimer
      molecular dynamics (BOMD) and density functional theory geometry optimizations.
      We find that Cu(II) binds to the imidazole N1 of His18, the deprotonated amides
      of Ser19 and Ser20, and an oxygen-based ligand provided by Ser20, either via its
      hydroxyl group or its backbone carbonyl, while Asn22 might also play a role as an
      axial ligand. Ser20 plays a crucial role in stabilizing Cu(II) coordination
      toward the C-terminal, providing a potential link between the S20G mutation
      associated with early onset of T2D, its impact in Cu binding properties, and
      hIAPP amyloid aggregation. Our study defines the nature of the coordination
      environment in the Cu(II)-hIAPP complex, revealing that the amino acid residues
      involved in metal ion binding are also key residues for the formation of beta
      sheet structures and amyloid fibrils. Cu(II) binding to hIAPP may lead to the
      coexistence of more than one coordination mode, which in turn could favor
      different sets of Cu-induced conformational ensembles. Cu-induced hIAPP
      conformers would display a higher energetic barrier to form amyloid fibrils,
      hence explaining the inhibitory effect of Cu ions in hIAPP aggregation. Overall,
      this study provides further structural insights into the bioinorganic chemistry
      of T2D.

PMID- 27704851
TI  - Amine-Mediated Transimination and Aromatization-Triggered Domino Reaction in the
      Synthesis of Polyfunctionalized 4-Aminoquinolines.
AB  - Dearomatization provides numerous possibilities for the development of new
      transformative modes of aromatic compounds. A conceptually novel metal-free
      multicomponent domino reaction of the dearomatized products of 2-alkynylanilines
      is developed. The reaction involves the secondary amine-mediated transimination
      with alpha-amino nitriles and subsequent aromatization-triggered cascade
      rearrangement, nucleophilic cyclization, and retro-Strecker reaction. This
      process provided a new practical method for the rapid synthesis of
      polyfunctionalized 4-aminoquinolines from readily available starting materials.

PMID- 27704850
TI  - Electromechanical Properties and Spontaneous Response of the Current in InAsP
      Nanowires.
AB  - The electromechanical properties of ternary InAsP nanowires (NWs) were
      investigated by applying a uniaxial tensile strain in a transmission electron
      microscope (TEM). The electromechanical properties in our examined InAsP NWs were
      governed by the piezoresistive effect. We found that the electronic transport of
      the InAsP NWs is dominated by space-charge-limited transport, with a I infinity
      V2 relation. Upon increasing the tensile strain, the electrical current in the
      NWs increases linearly, and the piezoresistance gradually decreases nonlinearly.
      By analyzing the space-charge-limited I-V curves, we show that the
      electromechanical response is due to a mobility that increases with strain.
      Finally, we use dynamical measurements to establish an upper limit on the time
      scale for the electromechanical response.

PMID- 27704852
TI  - Oxadiazolone-Enabled Synthesis of Primary Azaaromatic Amines.
AB  - Despite their tremendous synthetic and pharmaceutical utility, primary
      azaaromatic amines remain elusive for access based on a generally applicable C-H
      functionalization strategy. An oxadiazolone-enabled approach is reported for
      convenient entry into N-unsubstituted 1-aminoisoquinolines through Co(III)
      catalyzed redox-neutral, step-, atom-, and purification-economic C-H
      functionalization with alkynes. A 15N labeling experiment reveals the
      effectiveness of both oxadiazolone N atoms as directing sites. The installed
      primary amine can be harnessed as a synthetically useful handle for attachment of
      divergent appendages.

PMID- 27704853
TI  - Building Block Approach for the Synthesis of Sulfoximines.
AB  - A cross-coupling strategy for the preparation of novel sulfoximines via preformed
      sulfoximidoyl-containing building blocks has been developed. It allows obtaining
      a wide range of products in good yields under mild reaction conditions, and it
      can be applied in late-stage functionalizations, as demonstrated by the synthesis
      of a sulfoximine-based analogue of a recently reported potent valosine-containing
      protein inhibitor.

PMID- 27704854
TI  - Synthesis of the Azepinobisindole Alkaloid Iheyamine A Enabled by a Cross-Mannich
      Reaction.
AB  - The total synthesis of the azepinobisindole alkaloid iheyamine A is described.
      The successful strategy hinged on an intermolecular cross-Mannich reaction
      between 5-methoxy-3-acetoxyindole and a protected tryptamine to access an
      unsymmetrical 2,2'-bisindole, which was subsequently converted into iheyamine A
      via a deep-blue 3-indolone intermediate. VT 1H NMR infers that iheyamine A exists
      as a mixture of tautomers that undergo intermediate chemical exchange on the NMR
      time scale. The intermolecular cross-Mannich reaction described herein is a
      viable alternative to metal-catalyzed cross-coupling strategies commonly employed
      to access 2,2'-bisindoles.

PMID- 27704855
TI  - Electrostatically Driven Nanoballoon Actuator.
AB  - We demonstrate an inflatable nanoballoon actuator based on geometrical
      transitions between the inflated (cylindrical) and collapsed (flattened) forms of
      a carbon nanotube. In situ transmission electron microscopy experiments employing
      a nanoelectromechanical manipulator show that a collapsed carbon nanotube can be
      reinflated by electrically charging the nanotube, thus realizing an
      electrostatically driven nanoballoon actuator. We find that the tube actuator can
      be reliably cycled with only modest control voltages (few volts) with no apparent
      wear or fatigue. A complementary theoretical analysis identifies critical
      parameters for nanotube nanoballoon actuation.

PMID- 27704856
TI  - Aerobic Acetoxyhydroxylation of Alkenes Co-catalyzed by Organic Nitrite and
      Palladium.
AB  - An aerobic acetoxyhydroxylation of alkenes cooperatively catalyzed by organic
      nitrite and palladium at room temperature using clean and cheap air as the sole
      oxidant has been developed. Various vicinal diols, diacetoxyalkanes, and
      dihalogenoalkanes have been synthesized. The gram-scale synthesis has also been
      approached. Vicinal difluorination and dichlorolation products have also been
      achieved via this reaction.

PMID- 27704857
TI  - Precise Perforation and Scalable Production of Si Particles from Low-Grade
      Sources for High-Performance Lithium Ion Battery Anodes.
AB  - Alloy anodes, particularly silicon, have been intensively pursued as one of the
      most promising anode materials for the next generation lithium-ion battery
      primarily because of high specific capacity (>4000 mAh/g) and elemental
      abundance. In the past decade, various nanostructures with porosity or void space
      designs have been demonstrated to be effective to accommodate large volume
      expansion (~300%) and to provide stable solid electrolyte interphase (SEI) during
      electrochemical cycling. However, how to produce these building blocks with
      precise morphology control at large scale and low cost remains a challenge. In
      addition, most of nanostructured silicon suffers from poor Coulombic efficiency
      due to a large surface area and Li ion trapping at the surface coating. Here we
      demonstrate a unique nanoperforation process, combining modified ball milling,
      annealing, and acid treating, to produce porous Si with precise and continuous
      porosity control (from 17% to 70%), directly from low cost metallurgical silicon
      source (99% purity, ~ $1/kg). The produced porous Si coated with graphene by
      simple ball milling can deliver a reversible specific capacity of 1250 mAh/g over
      1000 cycles at the rate of 1C, with Coulombic efficiency of first cycle over
      89.5%. The porous networks also provide efficient ion and electron pathways and
      therefore enable excellent rate performance of 880 mAh/g at the rate of 5C. Being
      able to produce particles with precise porosity control through scalable
      processes from low-grade materials, it is expected that this nanoperforation may
      play a role in the next generation lithium ion battery anodes, as well as many
      other potential applications such as optoelectronics and thermoelectrics.

PMID- 27704858
TI  - Synthesis of 3-Sulfenylated Coumarins: BF3.Et2O-Mediated Electrophilic
      Cyclization of Aryl Alkynoates Using N-Sulfanylsuccinimides.
AB  - A simple and efficient metal-free sulfenylation/cyclization of aryl alkynoates
      has been developed, obtaining various 3-sulfenylated coumarins in moderate to
      excellent yields. In the presence of BF3.Et2O, the stable and readily accessible
      N-sulfanylsuccinimides were employed as electrophiles to induce the 6-endo-dig
      electrophilic cyclization of alkynoates. The reaction using substrates bearing a
      methoxy group on the phenoxy ring proceeded in an exclusively distinct pathway
      via either ipso sulfenylcyclization or sulfenylation of the phenoxy ring
      depending on the different locations of the methoxy substituent. The resulting 3
      sulfenylated coumarins can be readily transformed to 3-sulfinylated or 3
      sulfonylated coumarins under different oxidation conditions.

PMID- 27704859
TI  - Synthesis of Coumestrol and Aureol.
AB  - A total synthesis of coumestrol (1) and aureol (2) is described. The Perkin
      condensation of 2-bromo-4-hydroxylphenylacetic acid (6) and o
      hydroxybenzaldehydes (7) gave the corresponding 2'-bromo-3-arylcoumarins (9). A
      copper-catalyzed consecutive hydroxylation and aerobic oxidative coupling of 9
      under microwave conditions facilitated the total synthesis of 1 and 2,
      respectively, with spectroscopic data highly similar to those of natural
      products.

PMID- 27704860
TI  - Rh(III)-Catalyzed Cascade Annulation/C-H Activation of o-Ethynylanilines with
      Diazo Compounds: One-Pot Synthesis of Benzo[a]carbazoles via 1,4-Rhodium
      Migration.
AB  - A Rh(III)-catalyzed cascade annulation/C-H activation of o-ethynylanilines with
      diazo compounds has been developed. This concise method allows for the rapid
      formation of a number of benzo[a]carbazoles in high yields, exhibiting good
      functional group tolerance and scalability. The key to the success of this
      approach involves one C-N bond and two C-C bond formation, and an aryl-to-aryl
      1,4-rhodium migration.

PMID- 27704861
TI  - Probing Residue-Specific Water-Protein Interactions in Oriented Lipid Membranes
      via Solid-State NMR Spectroscopy.
AB  - Water plays a central role in membrane protein folding and function. It not only
      catalyzes lipid membrane self-assembly, but it is also affects the structural
      integrity and conformational dynamics of membrane proteins. Magic angle spinning
      (MAS) solid-state NMR is the technique of choice for measuring water
      accessibility of membrane proteins in a site-specific manner, providing a ruler
      for membrane protein topology and insertion within lipid bilayers. However,
      sensitivity and resolution of membrane protein samples for MAS experiments is
      often dictated by hydration levels, which affect membrane proteins structural
      dynamics. Oriented sample solid-state NMR (OS-ssNMR) is a complementary technique
      to determine both structure and topology of membrane proteins in liquid
      crystalline bilayers. Recent advancements in OS-ssNMR involve the use of oriented
      bicellar phases that have improved both sensitivity and resolution. Importantly,
      for bicelles formation and orientation, lipid bilayers must be well organized and
      hydrated, resulting in the protein's topology being similar to that found in
      native membranes. Under these conditions, the NMR resonances become relatively
      narrow, enabling a better separation of 1H-15N dipolar couplings and anisotropic
      15N chemical shifts with separated local field (SLF) experiments. Here we report
      a residue-specific water accessibility experiment for a small membrane protein,
      sarcolipin, embedded in oriented lipid bicelles as probed by new water-edited SLF
      experiments (WE-SLF). We show that sarcolipin's residues belonging to the
      juxtamembrane region are more exposed to the water-lipid interface than the
      corresponding membrane-embedded residues. The information that can be obtained
      from the WE-SLF experiments can be interpreted using a simple model based on spin
      diffusion theory and offers a complete characterization of membrane proteins in
      realistic membrane bilayer systems.

PMID- 27704862
TI  - Chloride Selective Macrocyclic Bisurea Derivatives with 2,2'-Binaphthalene
      Moieties as Spacers.
AB  - A cyclic bisurea derivative 2a has been successfully prepared from the
      corresponding diamine and diisocyanate in the presence of tetrabutylammonium
      chloride as a template. A more soluble cyclic bisurea 2b has also been prepared
      by introduction of sterically bulky tert-butyl groups. X-ray crystal analyses of
      [2a.Cl]- and [2b.Cl]- revealed that overall structure was saddle like and the
      chloride anion was located in the center of the cavity. The bound chloride anion
      was hydrogen bonded by four N-H of urea groups and weakly hydrogen bonded by four
      1-C-H of naphthyl groups, respectively. After removal of the bound chloride
      anions of [2b.Cl]- with silver nitrate, two different X-ray crystals of free 2b
      were obtained; one was intermolecular hydrogen bonded shrunken structure and the
      other was extended structure. Receptor 2b showed large binding ability for Cl-,
      however, the selectivity for Cl- against basic anions, such as AcO- and F-, has
      been insufficient. In aqueous MeCN, the association constant of 2b for Cl- was
      reduced but still large, and the selectivity for hydrophobic Cl- was greatly
      improved. In this solvent, 2b also selectively recognized alkaline metal chloride
      salts. Therefore, cyclic bisurea 2b is highly selective and effective Cl-
      selective receptor.

PMID- 27704863
TI  - Microwave Photodetection in an Ultraclean Suspended Bilayer Graphene p-n
      Junction.
AB  - We explore the potential of bilayer graphene as a cryogenic microwave
      photodetector by studying the microwave absorption in fully suspended clean
      bilayer graphene p-n junctions in the frequency range of 1-5 GHz at a temperature
      of 8 K. We observe a distinct photocurrent signal if the device is gated into the
      p-n regime, while there is almost no signal for unipolar doping in either the n-n
      or p-p regimes. Most surprisingly, the photocurrent strongly peaks when one side
      of the junction is gated to the Dirac point (charge-neutrality point CNP), while
      the other remains in a highly doped state. This is different to previous results
      where optical radiation was used. We propose a new mechanism based on the
      phototermal effect explaining the large signal. It requires contact doping and a
      distinctly different transport mechanism on both sides: one side of graphene is
      ballistic and the other diffusive. By engineering partially diffusive and
      partially ballistic devices, the photocurrent can drastically be enhanced.

PMID- 27704864
TI  - Scalable Regioselective Synthesis of Rhodamine Dyes.
AB  - A one-step, operationally simple protocol for the synthesis of isomerically pure
      rhodamine dyes from phthalaldehydic acids is reported. Using a mixture of 2,2,2
      trifluoroethanol and water as reaction media allows for clean and efficient
      formation of various rhodamines as a single isomer. This method was successfully
      applied to the synthesis of several isomerically pure rhodamines, including 6
      carboxytetramethylrhodamine and 6-carboxy-X-rhodamine (6-CXR) on gram scale. A
      simple, one-step, Pd-catalyzed hydroxycarbonylation approach to phthalaldehydic
      acids from appropriately substituted dihalobenzadehydes is also described.

PMID- 27704865
TI  - Effectiveness of Ayurvedic Massage (Sahacharadi Taila) in Patients with Chronic
      Low Back Pain: A Randomized Controlled Trial.
AB  - OBJECTIVES: Ayurveda is one of the oldest comprehensive healthcare systems
      worldwide. Ayurvedic massage and physical therapy are frequently used to treat
      patients with chronic pain syndromes and disorders of the musculoskeletal system.
      This study aimed to evaluate the effectiveness of Ayurvedic massage in
      nonspecific chronic low back pain by means of a randomized clinical trial.
      DESIGN: Sixty-four patients (mean age, 54.8 years; 49 women and 15 men) with
      chronic low back pain who scored >40 mm on a 100-mm visual analogue scale (VAS)
      were randomly assigned to a 2-week massage group with 6 hours of Ayurvedic
      massage and external treatment (n = 32) or to a 2-week local thermal therapy
      group (n = 32). The study observation period was 4 weeks, consisting of a 2-week
      intervention phase followed by a 2-week follow-up phase. OUTCOME MEASURES:
      Primary outcome measure was the change of mean pain (VAS) from baseline to week
      4. Secondary outcomes included pain-related bothersomeness, the Roland Disability
      Questionnaire, quality of life (Medical Outcomes Study 36-Item Short Form), the
      Hanover Functional Ability Questionnaire for measuring back pain-related
      disability, and psychological outcomes. Outcomes were assessed at baseline and
      after 2 and 4 weeks. RESULTS: Mean back pain (primary outcome) at week 2 was
      significantly reduced from 53.4 +/- 18.5 to 21.6 +/- 18.2 in the massage group
      and from 55.3 +/- 12.9 to 41.8 +/- 19.8 in the standard thermal therapy group
      (mean group difference, -18.7; 95% confidence interval, -28.7 to -8.7; p <
      0.001). While beneficial effects on pain-related bothersomeness and psychological
      well-being were also apparent, the Ayurvedic intervention did not improve
      function or disability in the short-term observation period. Both programs were
      safe and well tolerated. CONCLUSIONS: Ayurvedic external treatment is effective
      for pain-relief in chronic low back pain in the short term. Further studies with
      longer observation periods are needed to evaluate the long-term effects of the
      Ayurvedic external treatment approach on function and disability.

PMID- 27704866
TI  - Sorting by Cuts, Joins, and Whole Chromosome Duplications.
AB  - Genome rearrangement problems have been extensively studied due to their
      importance in biology. Most studied models assumed a single copy per gene.
      However, in reality, duplicated genes are common, most notably in cancer. In this
      study, we make a step toward handling duplicated genes by considering a model
      that allows the atomic operations of cut, join, and whole chromosome duplication.
      Given two linear genomes, [Formula: see text] with one copy per gene and
      [Formula: see text] with two copies per gene, we give a linear time algorithm for
      computing a shortest sequence of operations transforming [Formula: see text] into
      [Formula: see text] such that all intermediate genomes are linear. We also show
      that computing an optimal sequence with fewest duplications is NP-hard.

PMID- 27704868
TI  - Biomarkers and the sample matrix: challenges and opportunities.

PMID- 27704867
TI  - Biomarkers: more of a challenge for bioanalysis than expected.

PMID- 27704869
TI  - Caffeine effects on velocity selection and physiological responses during RPE
      production.
AB  - Caffeine (CAF) blunts estimated ratings of perceived exertion (RPE) but the
      effects on RPE production are unclear. This study examined effects of acute
      caffeine ingestion during treadmill exercise where participants exercised at
      prescribed RPE 4 and 7. Recreational runners (maximal oxygen consumption = 51.4
      +/- 9.8 mL.kg-1.min-1) (n = 16) completed a maximal treadmill test followed by
      trials where they selected treadmill velocity (VEL) (1% grade) to produce RPE 4
      and RPE 7 (10 min each). RPE production trials followed CAF (6 mg.kg-1) or
      placebo (PLA) (counterbalanced) ingestion. Participants were blinded to treadmill
      VEL but the Omni RPE scale was in full view. Repeated-measures ANOVA showed a
      main effect (trial) for VEL (CAF ~5 m.min-1 faster) for RPE 4 (p = 0.07) and RPE
      7 (p = 0.03). Mean heart rate and oxygen consumption responses were consistently
      higher for CAF but failed to reach statistical significance. Individual responses
      to CAF were labeled positive using a criterion of 13.4 m.min-1 faster for CAF
      (vs. PLA). Ten of 32 trials (31%) were positive responses. In these, systematic
      increases were observed for heart rate (~12 beats.min-1) and oxygen consumption
      (~5.7 mL.kg-1.min-1). Blunted/stable respiratory exchange ratio values at higher
      VEL for positive responders suggest increased free fatty acid reliance during
      CAF. In conlusion, mean results show a mild effect of CAF during RPE production.
      However, individual responses more clearly indicate whether a true effect is
      possible. Trainers and individuals should consider individual responses to ensure
      effectively intensity regulation.

PMID- 27704870
TI  - Commercial biomarker assays: friend and foe.
AB  - AIM: Commercial kits can provide a convenient solution for measuring circulating
      biomarkers to support drug development. However, their suitability should be
      assessed in the disease matrix of interest. METHODOLOGY: Twelve biomarkers were
      evaluated in samples from patients with rheumatoid arthritis. We used immunoassay
      kits from five vendors on three multiplexed platforms. Kit suitability was
      evaluated on the basis of detectability and prespecified performance acceptance
      criteria. RESULTS: Assays had varying levels of sensitivity and susceptibility to
      interference by matrix components. Only a few assays in the multiplexed kits were
      found to be suitable. In general, kits for analytes that passed our assay
      criteria showed good correlation between vendors. CONCLUSION: The data from this
      study demonstrate that the majority of assays on multiplexed kits evaluated
      either lacked sensitivity and/or had poor performance, which diminishes the
      utility of the multiplexing approach.

PMID- 27704871
TI  - The Association of Prenatal Tocolysis and Breastfeeding Duration.
AB  - BACKGROUND: To date there are no clinical studies analyzing potential effects of
      tocolytics on breastfeeding duration in humans. OBJECTIVES: The purpose of this
      study was to evaluate the association between beta 2 agonists prescribed for
      tocolysis during pregnancy and breastfeeding duration. METHODS: We conducted a
      cross-sectional questionnaire study of 114 mothers and filled in the
      questionnaire developed to directly address the goals of the study. RESULTS:
      There was a statistically significant difference between breastfeeding duration
      of mothers who were on tocolytics during pregnancy versus those who were not
      prescribed tocolytics (9.5 +/- 5.7 months versus 4.5 +/- 2.1 months) p < 0.001.
      In addition, hypogalactia was statistically significantly more prevalent in
      mothers with positive history versus mothers with negative history of tocolytic
      usage p < 0.001. CONCLUSION: The results of our study indicate that tocolytic
      treatment in pregnancy is associated with shorter breastfeeding duration and
      hypogalactia.

PMID- 27704872
TI  - MR imaging of the temporomandibular joint: comparison between acquisitions at 7.0
      T using dielectric pads and 3.0 T.
AB  - OBJECTIVES: To qualitatively and quantitatively compare MRI of the
      temporomandibular joint (TMJ) at 7.0 T using high-permittivity dielectric pads
      and 3.0 T using a clinical high-resolution protocol. METHODS: Institutional
      review board-approved study with written informed consent. 12 asymptomatic
      volunteers were imaged at 7.0 and 3.0 T using 32-channel head coils. High
      permittivity dielectric pads consisting of barium titanate in deuterated
      suspension were used for imaging at 7.0 T. Imaging protocol consisted of oblique
      sagittal proton density weighted turbo spin echo sequences. For quantitative
      analysis, pixelwise signal-to-noise ratio maps of the TMJ were calculated. For
      qualitative analysis, images were evaluated by two independent readers using 5
      point Likert scales. Quantitative and qualitative results were compared using t
      tests and Wilcoxon signed-rank tests, respectively. RESULTS: TMJ imaging at 7.0 T
      using high-permittivity dielectric pads was feasible in all volunteers.
      Quantitative analysis showed similar signal-to-noise ratio for both field
      strengths (mean +/- SD; 7.0 T, 13.02 +/- 3.92; 3.0 T, 14.02 +/- 3.41; two-sample
      t-tests, p = 0.188). At 7.0 T, qualitative analysis yielded better visibility of
      all anatomical subregions of the temporomandibular disc (anterior band,
      intermediate zone and posterior band) than 3.0 T (Wilcoxon signed-rank tests, p <
      0.05, corrected for multiple comparisons). CONCLUSIONS: MRI of the TMJ at 7.0 T
      using high-permittivity dielectric pads yields superior visibility of the
      temporomandibular disc compared with 3.0 T.

PMID- 27704873
TI  - Hyperoside ameliorates glomerulosclerosis in diabetic nephropathy by
      downregulating miR-21.
AB  - The purpose of this study was to investigate the therapeutic effects of
      hyperoside (Hyp) on glomerulosclerosis in diabetic nephropathy and its underlying
      mechanisms. Blood glucose, kidney mass, and renal function of mice were measured.
      Renal morphology was observed using hematoxylin and eosin, periodic acid -
      Schiff's, and Masson's trichrome stain. Fibronectin (FN) and collagen IV (COL IV)
      in kidney were determined by Western blot and immunohistochemical studies. Matrix
      metalloproteinases (MMP)-2 and -9 and tissue inhibitors of metalloproteinase
      (TIMP)-1 in renal tissues were detected on both the mRNA and protein levels.
      miRNA expression and artificial alterations by miRNA agomir transfection were
      evaluated to investigate the protective mechanism of Hyp in mesangial cells. Hyp
      effectively improved renal function and physiologic features of db/db mice. Hyp
      also ameliorated glomerulosclerosis by suppressing FN, COL IV, and TIMP-1
      expressions and promoting MMP-9 and MMP-2 expressions. The change in MMP-9 mRNA
      expression was inconsistent with that in protein levels in kidney, indicating
      that there was a post-transcriptional regulation. Further exploration in vitro
      showed that miR-21 was downregulated by Hyp, increasing expression of its target,
      MMP-9. These results suggest that Hyp can ameliorate glomerulosclerosis in
      diabetic nephropathy by downregulating miR-21 to increase expression of its
      target, MMP-9.

PMID- 27704875
TI  - Physiology-Invariant Meal Detection for Type 1 Diabetes.
AB  - BACKGROUND: Fully automated artificial pancreas systems require meal detectors to
      supplement blood glucose level regulation, where false meal detections can cause
      unnecessary insulin delivery with potentially fatal consequences, and missed
      detections may cause the patient to experience extreme hyperglycemia. Most
      existing meal detectors monitor various measures of glucose rate-of-change to
      detect meals where varying physiology and meal content complicate balancing
      detector sensitivity versus specificity. METHODS: We developed a novel meal
      detector based on a minimal glucose-insulin metabolism model and show that the
      detector is, by design, invariant to patient-specific physiological parameters in
      the minimal model. Our physiological parameter-invariant (PAIN) detector achieves
      a near-constant false alarm rate across all individuals and is evaluated against
      three other major existing meal detectors on a clinical type 1 diabetes data set.
      RESULTS: In the clinical evaluation, the PAIN-based detector achieves an 86.9%
      sensitivity for an average false alarm rate of two alarms per day. In addition,
      for all false alarm rates, the PAIN-based detector performance is significantly
      better than three other existing meal detectors. In addition, the evaluation
      results show that the PAIN-based detector uniquely (as compared with the other
      meal detectors) has low variance in detection and false alarm rates across all
      patients, without patient-specific personalization. CONCLUSIONS: The PAIN-based
      meal detector has demonstrated better detection performance than existing meal
      detectors, and it has the unique strength of achieving a consistent performance
      across a population with varying physiology without any individual-level
      parameter tuning or training.

PMID- 27704874
TI  - The Effect of Age on the Prevalence of Obesity among US Youth with Autism
      Spectrum Disorder.
AB  - BACKGROUND: We sought to assess the association between age and the prevalence of
      obesity among children with and without autism spectrum disorder (ASD) in the
      2011-2012 National Survey of Children's Health. METHODS: Analyses were restricted
      to 43,777 children, ages 10-17, with valid measures of parent-reported weight,
      height, and ASD status. Exploratory analyses describe the impact of sex,
      race/ethnicity, and household income on the relationship between age and obesity
      in ASD. RESULTS: Although the overall prevalence of obesity among children with
      ASD was significantly (p < 0.001) higher than among children without ASD (23.1%
      vs. 14.1%, 95% confidence interval for difference 3.6 to 14.4), child age
      significantly (p = 0.035) modified this difference. In a multivariable logistic
      regression analysis, adjusted for sex, race/ethnicity, and household income, the
      odds of obesity among children with ASD compared with children without ASD
      increased monotonically from ages 10 to 17 years. This pattern arose due to a
      consistently high prevalence of obesity among children with ASD and a decline in
      prevalence with advancing age among children without ASD. These findings were
      replicated using a propensity score analysis. Exploratory analyses suggested that
      the age-related change in obesity disparity between children with and without ASD
      may be further modified by sex, race/ethnicity, and household income.
      CONCLUSIONS: The patterns of prevalence observed with increasing age among
      children with and without ASD were unexpected. A better understanding of the
      etiological and maintenance factors for obesity in youth with ASD is needed to
      develop interventions tailored to the specific needs of these children.

PMID- 27704877
TI  - Waiting times.
AB  - In recent years, waiting times have been a major concern for most emergency
      departments.

PMID- 27704881
TI  - Neck care training can speed discharge.
AB  - Almost three out of five patients with suspected neck injury can be discharged at
      scene if emergency care staff have the right training, research findings suggest.

PMID- 27704876
TI  - CD4+Foxp3-IL-10+ Tr1 Cells Promote Relapse of Diffuse Large B Cell Lymphoma by
      Enhancing the Survival of Malignant B Cells and Suppressing Antitumor T Cell
      Immunity.
AB  - Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy. Complete
      remission can be achieved in most patients by conventional treatment with
      rituximab and chemotherapy. However, a subset of remission individuals will
      develop a relapsed disease for obscure reasons. CD4+Foxp3-IL-10+ cell (Tr1) is a
      novel cell subtype with the capacity to suppress pro-inflammatory responses, but
      has not been extensively studied in most tumors. In this study, we investigated
      the potential role of Tr1 cells in DLBCL. We found that compared to that in
      healthy controls, the frequency of Tr1 cells was significantly increased in DLBCL
      patients, even during complete remission. Further study showed that these Tr1
      cells were enriched in the CD25low/-Foxp3-CD49b+LAG-3+ fraction and could be
      developed in vitro from naive CD45RA+ CD4+ T cells. To examine the effect of Tr1
      upregulation, we cocultured the enriched in vitro-induced Tr1 cells (iTr1) with
      autologous primary DLBCL cells and CD3+ T cells and found that iTr1 cells both
      enhanced the survival of CD20+ DLBCL tumor cells and suppressed the antitumor
      response of CD3+ T cells through the production of IL-10. Furthermore, the
      frequency of CD4+Foxp3-IL-10+ Tr1 cells in DLBCL patients during complete
      remission is directly associated with the risk of relapse. Together, these
      results suggested that Tr1 cells contributed to tumor cell maintenance and may
      serve as a prognostic marker and therapeutic target.

PMID- 27704880
TI  - Message in a bottle.
AB  - K is a hard working staff nurse who likes to party. On an A&E festive do, she
      arrives at a restaurant in a group of staff who have already been drinking. After
      the meal, there are lots of empty wine bottles on K's table. She is bantering
      loudly with people, calling them 'bitches' or 'bastards'. She is also slapping
      people on their backs or punching them on their arms as she talks.

PMID- 27704883
TI  - Paediatric triage tape.
AB  - The 'paediatric triage tape' (PTT) is an easy-to-use major incident primary
      triage tool that is based on a modified triage sieve. The purpose of this study
      was to validate prospectively the PTT for use in paediatric major incidents.

PMID- 27704882
TI  - The tympanic thermometer.
AB  - This study aimed to evaluate the accuracy of a tympanic thermometer and its use
      on children in emergency departments.

PMID- 27704884
TI  - Conference Call.
AB  - The RCN emergency care forum of Wales is holding its national conference,
      entitled Reshaping Emergency Care, on May 19 at the University of Glamorgan,
      Pontypridd. Closing date for submissions is March 24. For more details, contact
      forum chair Wendy Hopkins by email: wendykhopkins@fsmail.net.

PMID- 27704886
TI  - Winning ways.
AB  - There are eight winners of December's Emergency Nurse reader offer, concerning
      the latest guidelines by the European Resuscitation Council (ERC).

PMID- 27704887
TI  - 'Cutbacks' prompt ens to quit training.
AB  - Cutbacks in NHS spending are forcing emergency care staff to drop out of a
      leadership training programme aimed at modernising the provision of urgent care.

PMID- 27704888
TI  - ?
AB  - Lines of communication: an inquiry into the July 7 London bombings heard that, in
      its immediate aftermath, staff had no idea what colleagues at other trusts were
      doing. Nurses told the Greater London Assembly's July 7 review committee last
      month how colleagues had been forced to run up and down the street to keep
      themselves up to date with events and find out how many casualties there were.
      Chief nurse at Great Ormond Street Hospital for Children Judith Ellis said that
      staff in her trust had treated casualties without knowing if other hospitals had
      been bombed.

PMID- 27704890
TI  - White paper.
AB  - The publication last month of the Department of Health's white paper on improving
      community health is set to spur on changes in emergency care provision, delegates
      heard.

PMID- 27704889
TI  - ?
AB  - Minor problems: the country's first walk-in centre for children with minor
      illnesses and injuries opened last month in Liverpool. One of three nurses
      working there, Karen Murch, pictured right with a young patient, predicted more
      choice for patients: 'Families will now have better access to paediatric
      expertise. It is also a chance for nurses to progress and develop fully their
      clinical skills.' All the nurses who run the Smithdown Children's NHS Walk-in
      Centre have just completed a 12-month advanced paediatric nurse practitioner
      programme at Liverpool John Moores University.

PMID- 27704896
TI  - Board's eye view.
AB  - During a trip last month to the Emergency Nurses Association (ENA) annual
      conference in Texas, I reflected on the benefits and autonomy we enjoy as nurses
      working in the UK healthcare system.

PMID- 27704897
TI  - ?
AB  - Breathe easy: as part of its Deadly Serious campaign, the charity, Asthma UK, is
      warning that people with the condition should carry an 'asthma attack card' at
      all times this winter. Survey results from Asthma UK show that, although 93 per
      cent of people in Britain know thatasthma attacks can be fatal, only half know
      what to do if they encounter them. The card provides basic information on what
      steps they can take. For details on how to obtain the cards, call 020 7786 5000.

PMID- 27704894
TI  - Associations of IGFBP3 Gene Polymorphism and Gene Expression with the Risk of
      Osteonecrosis of the Femoral Head in a Han Population in Northern China.
AB  - The critical roles of IGFBP3 in regulating the osteogenic and adipogenic
      differentiation of bone marrow mesenchymal stem cells strongly indicate its
      potential effects on the pathogenesis of osteonecrosis of the femoral head
      (ONFH). In this study, we investigated the association of IGFBP3 gene
      polymorphism and its protein expression with the development of ONFH to further
      explore its molecular pathogenesis. Ligase detection reactions and enzyme-linked
      immunosorbent assay were used to detect the polymorphisms of rs2453839[C/T] and
      rs3110697[A/G] and the serum protein expression of IGFBP3 gene in 182 cases and
      179 controls, respectively. The serum lipids level was also measured by automatic
      biochemistry analyzer. The results revealed that the recessive model of rs3110697
      and the dominant model of rs2453839 were significantly associated with the
      increased risk of ONFH (p = 0.048, p = 0.047, respectively). The genotypes of
      rs2453839 were also significantly related to the clinical stages of ONFH (p =
      0.017). More importantly, the serum protein expression of IGFBP3 and insulin-like
      growth factor 1 (IGF1) in the ONFH group were statistically increased compared
      with the control group (p = 0.044, p = 0.007). The serum triglyceride and low
      density lipoprotein cholesterol level in the ONFH group were significantly higher
      than the control group (p = 0.01, p = 0.005, respectively), but the serum high
      density lipoprotein cholesterol level of the ONFH group was dramatically lower
      than the control group (p = 0.0001). Our results showed that both the gene
      polymorphisms of IGFBP3 and the abnormal protein expression of serum IGFBP3 and
      IGF1 closely associated with the development of ONFH.

PMID- 27704898
TI  - Experience counts.
AB  - I am concerned about James Bird's article on the need for student nurses to
      receive specialised training in emergency care, published in the June issue of
      Emergency Nurse.

PMID- 27704899
TI  - Ministers warned over emergency care.
AB  - RCN Wales has warned ministers that they will make emergency care provision an
      'election issue' unless more government attention is paid to nurses' opinions.

PMID- 27704900
TI  - Skill mix tool for emergency care.
AB  - The RCN Emergency Care Association and the Faculty of Emergency Nursing have
      resumed development of a computer based skill mix calculation tool designed for
      emergency care settings.

PMID- 27704902
TI  - A sweet idea.
AB  - The charity, Diabetes UK, has recently launched its Measure Up campaign, which
      focuses on the relationship between waist size, obesity and the likelihood of
      developing diabetes mellitus.

PMID- 27704901
TI  - Children's care.
AB  - Deputy health minister Lewis Macdonald this month launched an emergency care
      framework for children and young people in Scotland.

PMID- 27704904
TI  - 'Up to 60' EDs to close as part of national reform.
AB  - Reform of emergency care services in England must be with the intention of
      improving services, not saving money, according to RCN Emergency Care Association
      chair Grant Williams.

PMID- 27704906
TI  - ECA steering committee elections.
AB  - Emergency nurses are voting this month to choose who will join the RCN Emergency
      Care Association (ECA) steering committee.

PMID- 27704905
TI  - Paediatric nurses.
AB  - It has been well documented recently that children require specially trained
      nurses to care for them, and that they should be treated in specially des-ignated
      areas in hospital.

PMID- 27704907
TI  - ED attendance increasing after GP change.
AB  - Increasing demands have been imposed on emergency care departments since GPs
      stopped being responsible for providing care out of hours, according to research
      published last month.

PMID- 27704908
TI  - Effect of exercise intensity and mode on acute appetite control in men and women.
AB  - The aim of this study was to compare the effects of exercise intensity on
      appetite control: relative energy intake (energy intake minus the energy
      expenditure of exercise; REI), hunger scores, and appetite-regulating hormones in
      men and women. Eleven men and 9 women were submitted to 4 experimental sessions:
      high-intensity intermittent all-out exercise (HIIE-A) for 60 * 8 s interspersed
      by 12 s of passive recovery; high-intensity intermittent exercise (HIIE) at 100%
      of maximal load attained in incremental test; steady-state exercise at 60% of
      maximal load, matched by work done; and a control session. Exercise was performed
      1.5 h after a standardized breakfast, and an ad libitum lunch was offered 4 h
      after breakfast. Blood concentration of insulin, cortisol, acylated ghrelin,
      peptideYY3-36, glucose, and hunger scores were measured when fasting, and at 1.5,
      2, 3.25, and 4 h of experiment. REI was lower in all exercises than in the
      control, without differences between exercises and sex showing no compensation in
      energy intake because of any exercise; the hunger scores were lower only in the
      exercises performed at higher intensity (HIIE and HIIE-A) compared with the
      control. The area under the curve of acylated ghrelin was lower in the HIIE-A
      when compared with the control. PeptideYY3-36 was higher in men than women and
      cortisol higher in women than men independently of the condition. Although high
      intensity exercises promoted a little more pronounced effects in the direction of
      suppressing the appetite, no differences were observed in REI, demonstrating that
      these modifications were not sufficient to affect energy intake.

PMID- 27704909
TI  - Zika Virus: Pathology From the Pandemic.
AB  - CONTEXT: -As the number of Zika virus (ZIKV) infections continues to grow, so,
      too, does the spectrum of recognized clinical disease, in both adult and
      congenital infections. Defining the tissue pathology associated with the various
      disease manifestations provides insight into pathogenesis and diagnosis, and
      potentially future prevention and treatment, of ZIKV infections. OBJECTIVE: -To
      summarize the syndromes and pathology associated with ZIKV infection, the
      implications of pathologic findings in the pathogenesis of ZIKV disease, and the
      use of pathology specimens for diagnosis of ZIKV infection. DATA SOURCES: -The
      major sources of information for this review were published articles obtained
      from PubMed and pathologic findings from cases submitted to the Infectious
      Diseases Pathology Branch at the Centers for Disease Control and Prevention.
      CONCLUSIONS: -Pathologic findings associated with ZIKV infection are
      characteristic but not specific. In congenital Zika syndrome, tissue pathology is
      due to direct viral infection of neural structures, whereas in Guillain-Barre
      syndrome, pathology is likely due to a postviral, aberrant host-directed immune
      response. Both fetal and placental pathology specimens are useful for ZIKV
      diagnosis by molecular and immunohistochemical assays; however, the implications
      of ZIKV detection in placentas from second- and third-trimester normal live
      births are unclear, as the potential postnatal effects of late gestational
      exposure remain to be seen.

PMID- 27704910
TI  - How Angiosarcoma and Facebook Changed My Life.

PMID- 27704911
TI  - ?
AB  - Fear of flying: the government has published updated guidance for category 1
      emergency care workers about a possible flu pandemic. The new guidance, designed
      to assist contingency planning, comes amid continuing concern that the 'bird flu'
      virus, H5N1, will develop an ability to pass easily between humans. Speaking this
      month, chief medical officer for England Sir Liam Donaldson said: 'Wherever in
      the world a flu pandemic starts, we must assume we will be unable to prevent it
      reaching the UK. When it does, its impact will be severe in the number of
      illnesses and the disruption to everyday life.' For details of the updated
      guidance, access www.preparingforemergencies.gov.uk/emergency/health.shtm.

PMID- 27704913
TI  - Doubts over future of ECA and FEN.
AB  - The future of the RCN Emergency Care Association (ECA) has been thrown into doubt
      amid plans to reform the college's membership structure.

PMID- 27704912
TI  - Emergency care strategy for wales.
AB  - The Welsh Assembly Government is expected this month to publish a draft of its
      long awaited Developing Emergency Care Strategy (DECS).

PMID- 27704914
TI  - Award winner.
AB  - Unit manager for the emergency assessment unit at Essex Rivers Health- care NHS
      Trust Rebecca Pulford (pictured) is among the latest nurses selected by The
      Health Foundation to join its leadership fellows award scheme.

PMID- 27704917
TI  - Celebrating success.
AB  - Emergency care staff who have achieved success through training have been invited
      to enter the Department for Education and Skills (DfES) 2006 national training
      awards.

PMID- 27704915
TI  - ?
AB  - Scrubbing up well: Peterborough and Stamford Hospitals NHS Foundation Trust has
      been praised for preparing its staff to deal with contamination incidents. The
      trust runs a one-day course, eight times a year, on which staff are taught how to
      treat patients who have been exposed to radiation or chemical contamination. RCN
      professional nurse adviser Mike Hayward praised the progress that the trust had
      made. 'Other trusts should take a lead from this,' he said. See also page 39.

PMID- 27704918
TI  - NMC election.
AB  - RCN Emergency Care Association (ECA) chair Grant Williams has been elected onto
      the Nursing and Midwifery Council (NMC).

PMID- 27704921
TI  - Wales: emergency care still in crisis.
AB  - Twelve months ago concern was expressed for the welfare of emergency nurses in
      Wales due to the unrelenting pressures in A&E.

PMID- 27704922
TI  - Patient choice.
AB  - It seems that, despite ministerial rhetoric about patient choice, the government
      is trying to persuade more patients to be treated in the community.

PMID- 27704924
TI  - Conference call.
AB  - Emergency nurses attending RCN congress in Bournemouth next month can attend an
      Emergency Nurse sponsored fringe event on surviving sepsis and reducing deaths
      through a care bundle approach. Congress lasts April 23-27.

PMID- 27704925
TI  - Nurse prescriber.
AB  - Nurse Prescriber, at www.nurse-prescriber.co.uk , is a peer reviewed, online
      educational service andinformation resource designed primarily for nurse
      prescribers and healthcare professionals in related fields.

PMID- 27704926
TI  - National formulary.
AB  - The tional British Na- Formulary has been available for some time in electronic
      form, at www.bnf.org/bnf/ , and is widely regarded as an up-to-date and
      authoritative resource on UK medicines.

PMID- 27704927
TI  - Skin problems.
AB  - If you ever need to find out more about skin rashes then try clicking on
      dermatlas.med.jhmiedu/derm/.

PMID- 27704929
TI  - Limb X-ray Interpretation Dorothe Larsen Limb X-ray Interpretation Peter Morris
      Whurr L29.99 230 1861564996 1861564996 [Formula: see text].
AB  - It has been a pleasure to review this incredibly useful and informative book.
      Larsen and Morris have put together a comprehensive text in an easy-to-read
      style, and their enthusiasm and passion for their subject is clear throughout.

PMID- 27704930
TI  - Drug calculations.
AB  - If you need to go back to basics and revise drug calculations, you could access
      www.geocities.com/Hot-Springs/8517/Quiz/quiz.htm.

PMID- 27704931
TI  - Selective extraction of proteins and other macromolecules from biological samples
      using molecular imprinted polymers.
AB  - The accurate determination of intact macromolecules in biological samples, such
      as blood, plasma, serum, urine, tissue and feces is a challenging problem. The
      increased interest in macromolecules both as candidate drugs and as biomarkers
      for diagnostic purposes means that new method development approaches are needed.
      This review charts developments in the use of molecularly imprinted polymers
      first for small-molecular-mass compounds then for proteins and other
      macromolecules. Examples of the development of molecularly imprinted polymers for
      macromolecules are highlighted. The two main application areas to date are
      sensors and separation science, particularly SPE. Examples include peptides and
      polypeptides, lysozyme, hemoglobin, ovalbumin, bovine serum albumin and viruses.

PMID- 27704933
TI  - Risk stratification scores.
AB  - Risk stratifi cation scores have been developed for various groups of patients,
      including those who have had major trauma or who need critical care. These tools
      have helped to improve patient care yet there have been few attempts to pro- duce
      a generic risk adjustment score for emergency medical admissions.

PMID- 27704935
TI  - Time to nurse.
AB  - It would be lovely but naive to believe that all children can live in safety,
      with all the love and support they need to nurture growth and imagination.

PMID- 27704936
TI  - A lifetime's service.
AB  - Clinical nurse specialist Sheila McGrane has retired after working for 33 years
      at Craigavon Area Hospital emergency department, Portadown.

PMID- 27704937
TI  - ?
AB  - Fine fellow: Tom Quinn has been made a fellow of the RCN for his contribution to
      research and practice of cardiac nursing, particularly in relation to nurses, and
      the treatment and care of patients with heart attack. Professor Quinn, who works
      with Coventry University and Staffordshire Ambulance Service NHS Trust, received
      the fellowship last month at RCN congress in Bournemouth.

PMID- 27704938
TI  - Rise in attendance put down to drink.
AB  - Most emergency care departments are experiencing an increase in the number of
      patients presenting with alcohol related conditions, survey results suggest.

PMID- 27704939
TI  - ?
AB  - Giving all they can: emergency care staff from Queen Mary's Sidcup NHS Trust,
      Kent, raised more than L1,800 for London Youth by taking part last month in City
      Challenge The event includes mountain biking, running and climbing, as well as
      team building exercises such as cracking codes and engineering tasks. Pictured
      left to right are staff nurses Claire Eastwood and Maddie Lovell, charge nurse
      Andrew Linney and senior house officer Shahid Sohail as they approach the
      finishing line.

PMID- 27704942
TI  - No more government ED support teams.
AB  - Emergency departments in England will no longer be offered expert advice by the
      government if they are struggling to meet or maintain performance targets.

PMID- 27704941
TI  - Poor awareness blamed for A&E overuse.
AB  - Confusion about out-of-hours care provision is continuing to fuel increased use
      of A&E, according to research published this month.

PMID- 27704943
TI  - Conference call.
AB  - The Ambulance Service Association is holding its Ambex 2006 conference and
      exhibition next month. The three-day conference, described as 'the annual event
      for professionals working in emergency care', starts in Harrogate on June 29. For
      details, call 020 7928 9620 or email rebecca.darby@asa.uk.net.

PMID- 27704946
TI  - Wrist fracture in children.
AB  - Wrist injuries are common among children presenting to emergency departments but,
      according to the authors of this study, there are no validated decision rules to
      help clinicians evaluate paediatric wrist trauma.

PMID- 27704944
TI  - Home truths for Reid.
AB  - Home secretary John Reid (pictured above right) joined hundreds of protesters
      last month to oppose plans that could mean the closure of Monklands Hospital A&E
      department, Lanarkshire.

PMID- 27704949
TI  - Visualizing the Architectures and Interactions of Nuclear Receptors.
AB  - Nuclear receptors (NRs) are master regulators of broad genetic programs in
      metazoans. These programs are regulated in part by the small-molecule ligands
      that bind NRs and modulate their interactions with transcriptional coregulatory
      factors. X-ray crystallography is now delivering more complete pictures of how
      the multidomain architectures of NR homo- and heterodimers are physically
      arranged on their DNA elements and how ligands and coactivator peptides act
      through these complexes. Complementary studies are also pointing to a variety of
      novel mechanisms by which NRs access their DNA-response elements within
      chromatin. Here, we review the new structural advances together with proteomic
      discoveries that shape our understanding of how NRs form a variety of functional
      interactions with collaborating factors in chromatin.

PMID- 27704948
TI  - Bmal1 Is Required for Normal Reproductive Behaviors in Male Mice.
AB  - Circadian rhythms synchronize physiological processes with the light-dark cycle
      and are regulated by a hierarchical system initiated in the suprachiasmatic
      nucleus, a hypothalamic region that receives direct photic input. The
      suprachiasmatic nucleus then entrains additional oscillators in the periphery.
      Circadian rhythms are maintained by a molecular transcriptional feedback loop, of
      which brain and muscle aryl hydrocarbon receptor nuclear translocator-like
      protein 1 (BMAL1) is a key member. Disruption of circadian rhythms by deletion of
      the BMAL1 gene (Bmal1 knockout [KO]) induces a variety of disease states,
      including infertility in males, due to unidentified mechanisms. We find that,
      despite normal sperm function, Bmal1 KO males fail to mate with receptive
      females, indicating a behavioral defect. Mating is dependent on pheromone
      detection, as are several other behaviors. We determined that Bmal1 KO males also
      fail to display aggression and avoidance of predator scent, despite intact main
      olfactory function. Moreover, the vomeronasal organ, a specialized pheromone
      responsive organ, was also functionally intact, as determined by calcium imaging
      in response to urine pheromone stimulus. However, neural circuit tracing using c
      FOS activation revealed that, although Bmal1 KO males displayed appropriate
      activation in the olfactory bulb and accessory olfactory bulb, the bed nucleus of
      the stria terminalis and the medial preoptic area (areas responsible for
      integration of copulatory behaviors) failed to activate highly in response to the
      female scent. This indicates that neural signaling in select behavioral centers
      is impaired in the absence of BMAL1, likely underlying Bmal1 KO male copulatory
      defects, demonstrating the importance of the BMAL1 protein in the maintenance of
      neural circuits that drive pheromone-mediated mating behaviors.

PMID- 27704951
TI  - RCN drawing up.
AB  - The RCN last month set up a series of focus groups charged with drawing up
      guidance on how nurses can best manage major incidents.

PMID- 27704952
TI  - Action needed for senior staff, delegates told.
AB  - Service managers have been urged to consider new ways of using the skills of
      senior emergency nurses.

PMID- 27704953
TI  - ?
AB  - Back to school: incoming president of the Emergency Nurses Association in the
      United States Nancy Bonalumi urged emergency nurses to consider taking up
      teaching roles in a bid to build healthcare capacity. She warned that, in the US,
      demographic trends suggest that the number of nurses will be '29 per cent below
      requirements by 2020' and that healthcare systems should no longer rely on nurses
      trained overseas: 'We need to be growing our own. My plea is, if you are thinking
      about becoming a professor, we need you'.

PMID- 27704954
TI  - Rapid assessment in 'majors'.
AB  - Introducing rapid assessment into 'majors' streams can reduce average waiting
      times for all patients by almost 60 per cent, delegates heard.

PMID- 27704955
TI  - 'Practical' guidance on managing major incidents.
AB  - College adviser Mike Hayward, who is leading the initiative with college council
      member Rob Sowney, said: 'We are not trying to recreate official government
      guidance. We have to make sure that the guidance is practical, easy to read and
      user friendly for staff on the shop floor.'

PMID- 27704950
TI  - Do Substance P and Neurokinin A Play Important Roles in the Control of LH
      Secretion in Ewes?
AB  - There is now general agreement that neurokinin B (NKB) acts via neurokinin-3
      receptor (NK3R) to stimulate secretion of GnRH and LH in several species,
      including rats, mice, sheep, and humans. However, the roles of two other
      tachykinins, substance P (SP) and neurokinin A, which act primarily via NK1R and
      NK2R, respectively, are less clear. In rodents, these signaling pathways can
      stimulate LH release and substitute for NKB signaling; in humans, SP is
      colocalized with kisspeptin and NKB in the mediobasal hypothalamus. In this
      study, we examined the possible role of these tachykinins in control of the
      reproductive axis in sheep. Immunohistochemistry was used to describe the
      expression of SP and NK1R in the ovine diencephalon and determine whether these
      proteins are colocalized in kisspeptin or GnRH neurons. SP-containing cell bodies
      were largely confined to the arcuate nucleus, but NK1R-immunoreactivity was more
      widespread. However, there was very low coexpression of SP or NK1R in kisspeptin
      cells and none in GnRH neurons. We next determined the minimal effective dose of
      these three tachykinins that would stimulate LH secretion when administered into
      the third ventricle of ovary-intact anestrous sheep. A much lower dose of NKB
      (0.2 nmol) than of neurokinin A (2 nmol) or SP (10 nmol) consistently stimulated
      LH secretion. Moreover, the relative potency of these three neuropeptides
      parallels the relative selectivity of NK3R. Based on these anatomical and
      pharmacological data, we conclude that NKB-NK3R signaling is the primary pathway
      for the control of GnRH secretion by tachykinins in ewes.

PMID- 27704956
TI  - Tributes paid.
AB  - Delegates paid tribute at the conference to several emergency nurses who have
      retired in recent months.

PMID- 27704958
TI  - ?
AB  - Shock value: the European Resuscitation Council has published new guidelines for
      the resuscitation of adults and children. These recommend giving 30 chest
      compressions for every two breaths, instead of 15 as recommend in the 2000
      guidelines. They also note that advances in defibrillator technology enable
      healthcare workers and trained laypeople to give electric shocks earlier and more
      effectively to people in cardiac arrest. The guidelines appear in the December
      issue of Resuscitation but are also published separately, both in full and pocket
      book form. See readers' offer on page 7.

PMID- 27704957
TI  - Call for tougher police action after attack on EN.
AB  - Emergency nurse Katie Detheridge has spoken out about the long lasting effects of
      an unprovoked attack by a man she was treating in A&E.

PMID- 27704959
TI  - Prize winners.
AB  - Three Emergency Nurse readers are celebrating after winning the reader offer in
      the November issue of the journal.

PMID- 27704960
TI  - A broader perspective.
AB  - It is always a delight to attend the annual conference of the RCN Emergency Care
      Association (ECA), especially as it involves meeting new people and catching up
      with acquaintances and friends.

PMID- 27704962
TI  - ?
AB  - HEAD INJURIES This study reviewed the frequency and quality of observations of
      100 patients with head trauma to see how staff adhered to guidelines from the
      National Institute for Clinical Excellence (NICE).

PMID- 27704961
TI  - Jehovah's witnesses.
AB  - Jehovah's Witnesses are known widely for believing in the absolute prohibition of
      accepting blood transfusions because they consider blood to be a nutrient. In
      emergency care settings, this can create ethical and legal dilemmas.

PMID- 27704963
TI  - Your letters.
AB  - Success or failure I write with reference to the role of nurse practitioners in
      UK A&E.

PMID- 27704964
TI  - Parental choice.
AB  - The authors of this study wanted to identify the factors that determine whether
      parents use paediatric nurse practitioner services in emergency departments.

PMID- 27704965
TI  - ECA to lobby government on controlled drugs.
AB  - The RCN Emergency Care Association (ECA) is calling for a re-write of patient
      group directions (PGDs) to allow nurses to administer controlled drugs in any
      care settings.

PMID- 27704966
TI  - Conference call.
AB  - The RCN paediatric emergency care group is holding a conference on May 24 in
      Leeds. Topics include international disaster response, fever management, sports
      injury management and mental health assessment. For details, contact
      janet.youd@cht.nhs.uk.

PMID- 27704967
TI  - NMC candidate.
AB  - Brian Boag, steering committee member of the RCN Emergency Care Association, is
      standing as a candidate in the Nursing and Midwifery Council (NMC) elections.

PMID- 27704968
TI  - Trolley waits up.
AB  - The number of patients waiting on trolleys in hospitals across Northern Ireland
      has increased almost ten-fold over the past six years.

PMID- 27704969
TI  - ?
AB  - Crash course: the Royal Berkshire Ambulance NHS Trust and The Vodafone UK
      Foundation are among the partners in a new initiative to raise awareness among
      young people about dangerous driving due to unsafe passenger behaviour. As part
      of the project, called Crash Impact, A level students visited a repair research
      centre to see the skills needed to cut open crashed cars and talk to emergency
      care workers about their experiences when attending such incidents.

PMID- 27704970
TI  - Opposition raised to walk-in centres.
AB  - The prospect of rolling out NHS walk-in centres across Wales met opposition from
      emergency nurses last month despite it receiving a unanimous vote in favour at
      the National Assembly.

PMID- 27704971
TI  - Sports injuries.
AB  - Another US site with detailed explanations of common sports injuries can be found
      at www.sportsmedofindiana.com/.

PMID- 27704972
TI  - Funding rethink urged Opposition raised to walk-in centres.
AB  - The Department of Health has been urged to rethink how the new Payment by Results
      funding arrangements affect emergency care. The Department of Health has been.

PMID- 27704973
TI  - Conference call.
AB  - The Resuscitation Council (UK) is expected to launch new cardiopulmonary
      resuscitation guidelines in January at its 16th annual scientific symposium. The
      conference is on January 19 and is being held at Hammersmith Hospital, London. >
      For further details, access www.resus.org.uk.

PMID- 27704974
TI  - Respect for refugees.
AB  - At the end of a busy day, most of us can return home to our 'refuge', where we
      can unwind and relax in a safe environment. This is a place that feels secure to
      us, where we can surround ourselves with familiar people and belongings. For many
      of us, our refuge holds part of our identity.

PMID- 27704975
TI  - Web scan.
AB  - This selection of sites focuses on musculoskeletal and sports related
      information.

PMID- 27704976
TI  - Tips for mountain bikers.
AB  - More useful tips, this time aimed at mountain bikers, can be found at
      www.utahmountainbiking.com/firstaid/index.htm This site has recommendations on
      first aid including what equipment, including dressings, are useful in a first
      aid pack.

PMID- 27704977
TI  - Injury prevention.
AB  - For a start, why not suggest to patients that they access
      www.brianmac.demon.co.uk/index.htm , whose website contains training tips and
      advice about injury prevention?

PMID- 27704978
TI  - Updated Manchester triage system published this month.
AB  - The Manchester Triage Group this month publishes an updated version of its
      internationally renowned system for prioritising emergency care patients.

PMID- 27704979
TI  - Evaluating the introduction of a paediatric emergency nurse practitioner service.
AB  - By January 2005, the Department of Health expected emergency departments (EDs) in
      England to see 98 per cent of their patients within four hours ( DH 2001 ).

PMID- 27704980
TI  - Musculoskeletal evaluation.
AB  - Another useful resource comes from the Arthritis Research Council (ARC), which
      has several publications designed to improve musculoskeletal evaluation.

PMID- 27704981
TI  - Joint tests.
AB  - Another UK site is at www.jointzone.org.uk/ This is good for updating
      musculoskeletal assessment skills and contains video clips of special joint
      tests.

PMID- 27704982
TI  - Rehab regimes.
AB  - A comprehensive site aimed at sports therapists can be found at
      www.sportsinjuryclinic.net/index.htm.

PMID- 27704983
TI  - Revision and support.
AB  - For more experienced practitioners, there are several sites that can be used for
      revision and support. These include www.exrx.net/Lists/Directory.html , part of
      an American sports site aimed to teach exercise regimes.

PMID- 27704985
TI  - Choices in Treatment Integrity:Considering the Protocol and Consultant
      Recommendations in Child and Adolescent Therapy.
AB  - Codifying a complex treatment intervention into a manual necessarily involves
      simplifying procedures, possibly resulting in developer and expert adaptations
      that align with but are not fully consistent with the manualized content. This
      study evaluated the integrity of an evidence-based treatment to two information
      sources (i.e., an expert consultant and the treatment manual) within youth
      community mental health settings. Consultant recommendations were compared with
      manual-prescribed therapy procedures, which identified instances of agreement
      between the sources as well as consultant adaptations. To determine clinicians'
      integrity to each source, clinician-reported therapy procedures were compared
      with consultant recommendations and manual prescriptions. Participants consisted
      of 30 clinicians, five consultants, and 78 youths (53% male; M age = 9.73 years,
      SD = 2.84; 81% Latino). Findings indicated that consultants generally recommended
      content from the manual but also made frequent adaptations that involved changing
      the sequence or problem focus of practices and adding additional content.
      Clinicians followed both information sources in a majority of their sessions when
      these sources agreed but were more likely to follow only one or neither source
      when they disagreed. Findings suggest that consultants often make adaptations to
      the manual and that clinicians are more likely to employ recommendations from the
      manual and/or consultant when the information sources are in agreement. Although
      it is as yet unclear whether consultant recommendations are effective when they
      differ from the prescriptions of the manual, results from this study indicate
      that information sources that supplement treatment manuals may benefit clinical
      decision making.

PMID- 27704986
TI  - Structure-based discovery and binding site analysis of histamine receptor
      ligands.
AB  - INTRODUCTION: The application of structure-based drug discovery in histamine
      receptor projects was previously hampered by the lack of experimental structures.
      The publication of the first X-ray structure of the histamine H1 receptor has
      been followed by several successful virtual screens and binding site analysis
      studies of H1-antihistamines. This structure together with several other recently
      solved aminergic G-protein coupled receptors (GPCRs) enabled the development of
      more realistic homology models for H2, H3 and H4 receptors. Areas covered: In
      this paper, the authors review the development of histamine receptor models and
      their application in drug discovery. Expert opinion: In the authors' opinion, the
      application of atomistic histamine receptor models has played a significant role
      in understanding key ligand-receptor interactions as well as in the discovery of
      novel chemical starting points. The recently solved H1 receptor structure is a
      major milestone in structure-based drug discovery; however, our analysis also
      demonstrates that for building H3 and H4 receptor homology models, other GPCRs
      may be more suitable as templates. For these receptors, the authors envisage that
      the development of higher quality homology models will significantly contribute
      to the discovery and optimization of novel H3 and H4 ligands.

PMID- 27704989
TI  - Trying your patience.
AB  - A sign the world has gone mad? What was happening to my patients today? They
      seemed to be getting lost when I sent them for X-ray. I'd given the same
      directions as normal, there had been no secret muggers hiding in the hospital
      corridors and, as far as I know, no problems with space-time dimensions in our
      particular corner of the universe.

PMID- 27704988
TI  - Patient transfers.
AB  - This study was under-taken to explore the communication process between ED and
      intensive care unit (ICU) staff during transfers of critically ill patients.

PMID- 27704990
TI  - Your letters.
AB  - Addressing unnecessary attendances Last month at the RCN Emergency Care
      Association annual conference, I presented a paper entitled Dispelling the myths:
      a direct challenge for NHS Direct.

PMID- 27704992
TI  - Medication errors.
AB  - The authors of this study wanted to test their idea that, because medication
      errors are common in EDs and because there can be large variations in child ren's
      weight, such errors are more likely to occur among paediatric patients.

PMID- 27704994
TI  - Good communication.
AB  - Good communication is essential to providing high quality patient care especially
      in the often chaotic environment of emergency departments (EDs).

PMID- 27704995
TI  - Poor care for the severely injured.
AB  - Nearly half of severely injured patients receive poor quality care, according to
      a report by the National Confidential Enquiry into Patient Outcome and Death.

PMID- 27704996
TI  - ?
AB  - Driving the message home: black cabs half painted as ambulances have hit the
      streets in Birmingham, Liverpool, London and Manchester as part of the
      government's latest Know Your Limits safer drinking publicity campaign. The taxis
      form part of a wider advertising effort that also includes a fleet of 1,000 buses
      emblazoned with a bus route style map. Using the same 'Don't let a good night
      turn into a bad one' strapline, the journey depicted on the side of the buses
      terminates at an A&E department. Home Office minister Vernon Coaker (pictured)
      said: 'At this time of year when people will be out having a good time, these
      vehicles will, I hope, make people think twice about having one drink too many'.

PMID- 27704997
TI  - Research launched into staff awareness of bioterrorism threat.
AB  - Emergency nurse practitioner Andrew Linney is calling on emergency nurses to help
      him with research into bioterrorism knowledge and confidence among A&E staff.

PMID- 27704998
TI  - Emergency care's global village.
AB  - In attending the RCN Emergency Care Association (ECA) annual conference this
      year, it was clear that emergency nurses and other healthcare professionals are
      well positioned to lead the way in making change.

PMID- 27704999
TI  - Proposal for ED 'patient charters'.
AB  - Emergency departments throughout the UK may soon be issued a 'patient charter' to
      help ensure that staff meet public expectations.

PMID- 27705000
TI  - Nick Lipley reports from this year's RCN emergency care association.
AB  - Emergency nurses have been called on to 'involve and empower' patients so they
      can help develop new services.

PMID- 27705001
TI  - Feedback needed on managing people who self harm.
AB  - Most emergency department staff think they know too little about people who self
      harm to be able to help them, according to research presented at the conference.

PMID- 27705003
TI  - Steroid glycosides from the starfish Pentaceraster gracilis.
AB  - Using combined chromatographic separations, two new steroid glycosides namely
      pentacerosides A (1) and B (2), and four known compounds were isolated from the
      methanol extract of the starfish Pentaceraster gracilis. Their structures were
      determined on the basis of spectroscopic data (1H and 13C NMR, HSQC, HMBC, 1H-1H
      COSY, ROESY, and FT-ICR-MS) and by comparing obtained results to the literature
      values. Among the isolated compounds, only maculatoside (5) showed significant
      cytotoxic effect against Hep-G2 (IC50 = 16.75 +/- 0.69 MUM) and SK-Mel2 (IC50 =
      19.44 +/- 1.45 MUM) cell lines and moderate effect on KB (IC50 = 36.53 +/- 0.78
      MUM), LNCaP (IC50 = 39.75 +/- 3.34 MUM), and MCF7 (IC50 = 47.34 +/- 7.01 MUM)
      cell lines.

PMID- 27705002
TI  - Temperament Distinguishes Persistent/Recurrent from Remitting Anxiety Disorders
      Across Early Childhood.
AB  - Up to 20% of preschool-age children meet criteria for anxiety disorders and, for
      a large subset, anxiety appears to persist throughout early childhood. However,
      little is known about which factors predict persistence/recurrence of anxiety in
      young children. Temperament, including behavioral inhibition (BI), negative
      emotionality (NE), and positive emotionality (PE), predict the onset of anxiety
      disorders, but to our knowledge no study has examined whether temperament
      predicts the course of anxiety in young children. From a community sample of 3
      year-olds, we identified 89 children (79.8% White, non-Hispanic; 41.6% female)
      who met criteria for an anxiety disorder and examined whether observed and parent
      reported BI, NE, and PE at age 3 distinguished children who continued to meet
      criteria for an anxiety disorder from those who remitted by age 6. Higher levels
      of BI and lower levels of PE assessed in the laboratory and higher parent
      reported BI and shyness and lower surgency at age 3 significantly predicted
      persistence/recurrence of anxiety disorders from age 3 to 6. These data are the
      first to demonstrate the influence of temperament on the course of anxiety
      disorders in young children. These findings can enhance assessment and treatment
      of anxiety by focusing intervention efforts on children who are at risk for
      persistent or recurring anxiety rather than children who are displaying
      transient, and possibly developmentally normative, anxiety.

PMID- 27705004
TI  - CRP/IL-6/IL-10 Single-Nucleotide Polymorphisms Correlate with the Susceptibility
      and Severity of Community-Acquired Pneumonia.
AB  - OBJECTIVE: To explore the associations of single-nucleotide polymorphisms (SNPs)
      of the C-reactive protein (CRP), interleukin 6 (IL-6) and IL-10 genes with
      susceptibility and severity of community-acquired pneumonia (CAP). MATERIALS AND
      METHODS: Two hundred seventy-nine CAP patients were selected for the case group
      and 156 healthy individuals for the control group. Polymerase chain reaction
      restriction fragment length polymorphism was performed for genotyping of CRP
      +1059G/C (rs1800947) and +1846C/T (rs1205), IL-6 -597G/A (rs1800797) and -572C/G
      (rs1800796), and IL-10 -592C/A (rs1800872) and -1082G/A (rs1800896). According to
      CURB-65 score, the patients were assigned into the severe community-acquired
      pneumonia (SCAP) and non-SCAP groups. RESULTS: The frequencies of the CRP
      +1846C/T (rs1205) (CT+TT) genotypes and T allele, the IL-6 -597G/A (rs1800797)
      (AA+AG) genotypes and A allele, and the IL-10 -592C/A (rs1800872) (CA+AA)
      genotypes and A allele were higher in the case group than the control group.
      Furthermore, the frequencies of the CRP +1846C/T (rs1205) (CT+TT) genotypes and T
      allele, the IL-6 -597G/A (rs1800797) A allele, and the IL-10 -592C/A (rs1800872)
      (CA+AA) genotypes and A allele were higher in the SCAP group than in the non-SCAP
      group. CONCLUSION: The CRP +1846C/T (rs1205), IL-6 -597G/A (rs1800797), and IL-10
      -592C/A (rs1800872) may be associated with the susceptibility and severity of
      CAP.

PMID- 27705006
TI  - Effects of Nintendo WiiTM Training on Occupational Performance, Balance, and
      Daily Living Activities in Children with Spastic Hemiplegic Cerebral Palsy: A
      Single-Blind and Randomized Trial.
AB  - OBJECTIVE: This study aimed at assessing how the addition of Nintendo WiiTM (NW)
      system to the traditional therapy influences occupational performance, balance,
      and daily living activities in children with spastic hemiplegic Cerebral Palsy
      (CP). MATERIALS AND METHODS: The present study is a single-blind and randomized
      trial involving 24 children aged 6-14 years, classified as level I or II on the
      Gross Motor Function Classification System. The children were allocated into two
      groups: an intervention and a control group, and their families participated in
      the study. The activity performance analysis of the children was undertaken by
      using the Canadian Occupational Performance Measure (COPM), functional balance
      was measured with the Pediatric Balance Scale (PBS), and activities of daily
      living were assessed with Pediatric Evaluation of Disability Inventory (PEDI).
      Twenty-four children with CP were randomly divided into two groups: intervention
      (n = 12) and control group (n = 12). All children in both groups continued their
      traditional physiotherapy program twice a week, 45 minutes per session, whereas
      the participants in the intervention group, additionally, were trained with NW,
      two other days of the week for 12 weeks, with each session lasting for 30
      minutes. RESULTS: Self-care, mobility, PEDI total, PBS, and performance of COPM
      scores increased in the NW group after intervention. Self-care, mobility, and
      total PEDI increased in the control group as well. However, there was no
      statistically significant difference found between the groups, except for PBS (P
      < 0.05). CONCLUSIONS: NW contributed to the implementation of occupational
      performance, daily living activities, and functional balance. We recommend that
      NW could be used in the rehabilitation program to engage play-based activities
      with fun.

PMID- 27705005
TI  - Future therapeutic potential of SAP-1 in inflammatory bowel diseases.

PMID- 27705007
TI  - The variation in high sensitive cardiac troponin concentration during
      haemodialysis treatment is not similar to the biological variation observed in
      stable end stage renal disease patients.
AB  - BACKGROUND: Cardiovascular mortality is high in end stage renal disease (ESRD).
      This study aimed to: (1) calculate within-week within- and between-subject
      biological variation (CVI and CVG) for hs-cTn in ESRD; (2) determine the
      magnitude of hs-cTn concentration changes during haemodialysis (HD) treatment;
      and (3) compare the CVI and CVG to the within and between-subject variation of
      cTn concentration changes during HD treatments (CVDIFF-I and CVDIFF-G). METHODS:
      Serum samples were collected from 20 patients before and after 10 consecutive HD
      treatments. cTn were measured using the hs-cTnT (Roche Diagnostics) and the hs
      cTnI (Abbott Diagnostics). The CVA, CVI, CVG, CVDIFF-I and CVDIFF-G, were
      estimated using nested ANOVA. RESULTS: The within-week data showed hs-cTnT CVA,
      CVI and CVG of 1.6, 7.3 and 94.4%. Reference change values (RCV) were estimated
      to -18.7-23.0%. The Index of individuality (II) was 0.08. Corresponding values
      for hs-cTnI were 5.3, 13.2 and 142.4%, whilst the RCV was -32.5-48.2% and the II
      was 0.10. The mean concentration of cTn decreased by -6.4% (hs-cTnT) and -7.6%
      (hs-cTnI) during HD treatment. The CVDIFF-I and CVDIFF-G was 4.2 and 6.3% for hs
      cTnT, and 10.7 and 9.4% for hs-cTnI. The RCVDIFF was -18.2-5.4% (hs-cTnT) and 
      39.0-23.8% (hs-cTnI), respectively, and the IIDIFF-values were 0.7 and 1.3.
      CONCLUSIONS: The CVI and CVG are similar to earlier findings. Mean hs-cTn
      concentrations decreased during HD. The within-subject hs-cTn variation during HD
      is similar to the between-subject variation, i.e. determining a cut-off value for
      hs-cTn changes during HD may be useful.

PMID- 27705008
TI  - A systematic review of resonant voice therapy.
AB  - PURPOSE: The purpose of this study is to systematically review the literature on
      resonant voice therapy and to evaluate the level of evidence on the effectiveness
      of using resonant voice therapy in treating dysphonia. METHOD: Refereed journal
      papers from 1974 to 2014 were retrieved and reviewed by two independent reviewers
      using the keywords "Humming, Resonance, Resonant Voice, Semi-occluded or closed
      tube phonation" using available database systems. Quality of evidence was
      evaluated by using the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE). RESULT: Thirteen papers met the search criteria. Nine papers
      were selected by the two reviewers. Two of the papers were randomised-controlled
      studies and the other seven were observational studies. At least four types of
      resonant voice therapies were described. They included the Lessac-Madsen Resonant
      Voice Therapy, Y-Buzz, Resonance Therapy and Humming. The overall level of
      quality of evidence was graded as "moderate". CONCLUSION: There were limited
      studies that investigated the effectiveness of resonant voice therapy. Most
      studies were small-scale uncontrolled observational studies with the inclusion of
      only small samples or specific populations. There is clearly a need for more
      large-scale randomised controlled studies with a wider range of populations to
      provide further evidence on the effectiveness of resonant voice training for
      different populations.

PMID- 27705009
TI  - Treatment Precedes Positive Symptoms in North American Adolescent and Young Adult
      Clinical High Risk Cohort.
AB  - Early intervention for psychotic disorders, a growing international priority,
      typically targets help-seeking populations with emerging psychotic ("positive")
      symptoms. We assessed the nature of and degree to which treatment of individuals
      at high risk for psychosis preceded or followed the onset of positive symptoms.
      The North American Prodrome Longitudinal Study-2 collected psychosocial treatment
      histories for 745 (98%) of 764 high-risk participants (M age = 18.9, 57% male,
      57.5% Caucasian, 19.1% Hispanic) recruited from 8 North American communities.
      Similar to prior findings, 82% of participants reported psychosocial treatment
      prior to baseline assessment, albeit with significant variability across sites
      (71%-96%). Participants first received treatment a median of 1.7 years prior to
      the onset of a recognizable psychosis-risk syndrome. Only one fourth sought
      initial treatment in the year following syndrome onset. Although mean sample age
      differed significantly by site, age at initial treatment (M = 14.1, SD = 5.0) did
      not. High rates of early treatment prior to syndrome onset make sense in light of
      known developmental precursors to psychotic disorders but are inconsistent with
      the low rates of treatment retrospectively reported by first-episode psychosis
      samples. Findings suggest that psychosis risk studies and clinics may need to
      more actively recruit and engage symptomatic but non-help-seeking individuals and
      that community clinicians be better trained to recognize both positive and
      nonspecific indicators of emerging psychosis. Improved treatments for nonspecific
      symptoms, as well as the characteristic attenuated positive symptoms, are needed.

PMID- 27705010
TI  - Therapeutic effects of intensive voice treatment (LSVT LOUD(r)) for children with
      spastic cerebral palsy and dysarthria: A phase I treatment validation study.
AB  - PURPOSE: The aim of the present study was to validate and extend the evaluation
      of treatment outcomes following LSVT LOUD(r) in children with dysarthria
      secondary to cerebral palsy (CP). METHOD: Seven children (5 females, 6-10 years)
      with spastic quadriplegia and dysarthria received LSVT LOUD. Outcomes included:
      (a) quantitative and qualitative indices of communication and social functioning
      representing therapeutic effects and (b) features of the acoustic signal
      representing physiological effects on the speech mechanism. A matched group of
      typically developing children served as controls. Testing occurred just prior to
      (PRE), immediately following (POST), and at 12 weeks post-treatment (FUP).
      RESULT: Expert listeners preferred voice quality and articulatory precision of
      children with CP at FUP as compared to PRE. Acoustic data indicated improvements
      on select measures of vocal functioning at POST with some maintenance at FUP.
      Single word intelligibility improved immediately POST, but was not maintained at
      FUP. Parents rated positive changes in characteristics of voice and speech and
      qualitative changes in communication at both POST and FUP. CONCLUSION: The
      present study validated some of the previous LSVT LOUD outcomes in children with
      dysarthria and CP and extended our understanding of therapeutic effects through
      qualitative data obtained from extensive parent interviews.

PMID- 27705011
TI  - Interprofessional education in maternity services: Is there evidence to support
      policy?
AB  - Against a backdrop of poor maternity and obstetric care, identified in the
      Morecambe Bay Inquiry, the UK government has recently called for improvements and
      heralded investment in training. Given the complex mix of professionals working
      closely together in maternity services addressing the lack of joined up
      continuing professional development (CPD) is necessary. This led us to ask
      whether there is evidence of IPE in maternity services. As part of a wider
      systematic review of IPE, we searched for studies related to CPD in maternity
      services between May 2005 and June 2014. A total of 206 articles were identified
      with 24 articles included after initial screening. Further review revealed only
      eight articles related to maternity care, none of which met the inclusion
      criteria for the main systematic review. The main reasons for non-inclusion
      included weak evaluation, a focus on undergraduate IPE, and articles referring to
      paediatric/neonatal care only. Fewer articles were found than anticipated given
      the number of different professions working together in maternity services. This
      gap suggests further investigation is warranted.

PMID- 27705012
TI  - How patient-controlled sedation is adopted in clinical practice of sedation for
      endoscopic retrograde cholangiopancreatography? A prospective study of 1196
      cases.
AB  - OBJECTIVE: Patient-controlled sedation (PCS) has been shown to be a valid choice
      for sedation during endoscopic retrograde cholangiopancreatography (ERCP) in
      randomized studies. However, large-scale studies are lacking. MATERIAL AND
      METHODS: A single center, prospective observational study to determine how
      sedation for ERCP is administered in clinical setting. All 956 patients
      undergoing 1196 ERCPs in the endoscopy unit of Helsinki University Central
      Hospital 2012-2013, methods of sedation and adverse events associated with
      different sedations were recorded. RESULTS: PCS was attempted a total of 685
      times (57%), successful use of PCS was achieved with 526 patients (77% of
      attempts). PCS device was operated by the anesthesiologist or anesthesia nurse
      268 times (22%). PCS was more likely chosen for younger (80.6% for < =60 years
      vs. 63.8% for >60 years, p<.001) patients and by trainee anesthetists.
      Anesthesiologist administered propofol sedation was used 240 times (20%). The
      risk of failure of PCS was increased, if systolic arterial pressure was <90 mmHg,
      dosage of PCS >17 ml, duration of procedure exceeded 23 min. The risk of failure
      was lower in patients with primary sclerosing cholangitis (PSC) and if sedation
      was deeper RASS < =-2. Uneventful PCS was associated with less respiratory and
      cardiovascular depression than other methods. There were no statistically
      significant differences in safety profiles with all the methods of sedation.
      CONCLUSIONS: PCS is readily implemented in clinical practice, is suitable for
      younger and low-risk patients and is associated with less cardiorespiratory
      adverse effects.

PMID- 27705014
TI  - Managing Spinal Cord Injury: The first 48 hoursEditor: Managing Spinal Cord
      Injury: The first 48 hours Paul Harrison Spinal Injuries Association 2007 106
      :L15.00 978 0 954713 21 8 [Formula: see text].
AB  - This is an excellent and concise book that is not only ideal for use while
      working but also sufficiently detailed to be used for reference.

PMID- 27705015
TI  - Conference call.
AB  - The RCN paediatric emergency care conference is to be held on December 12 at the
      college headquarters in London. Topics include managing children with asthma and
      caring for young people with mental health problems.

PMID- 27705013
TI  - Colorectal Adenomatous Polyposis: Heterogeneity of Susceptibility Gene Mutations
      and Phenotypes in a Cohort of Italian Patients.
AB  - AIMS: Colorectal adenomatous polyposis entailing cancer predisposition is caused
      by constitutional mutations in different genes. APC is associated with the
      familial adenomatous polyposis (FAP/AFAP) and MUTYH with the MUTYH-associated
      polyposis (MAP), while POLE and POLD1 mutations cause the polymerase proofreading
      associated polyposis (PPAP). METHODS: We screened for mutations in patients with
      multiple adenomas/FAP: 121 patients were analyzed for APC and MUTYH mutations,
      and 36 patients were also evaluated for POLE and POLD1 gene mutations. RESULTS:
      We found 20 FAP/AFAP, 15 MAP, and no PPAP subjects: pathogenic mutations proved
      to be heterogeneous, and included 5 APC and 1 MUTYH novel mutations. The mutation
      detection rate was significantly different between patients with 5-100 polyps and
      those with >100 polyps (p = 8.154 * 10-7), with APC mutations being associated
      with an aggressive phenotype (p = 1.279 * 10-9). Mean age at diagnosis was lower
      in FAP/AFAP compared to MAP (p = 3.055 * 10-4). Mutation-negative probands showed
      a mean age at diagnosis that was significantly higher than FAP/AFAP (p = 3.46986
      * 10-7) and included 45.3% of patients with <30 polyps and 70.9% of patients with
      no family history. CONCLUSIONS: This study enlarges the APC and MUTYH mutational
      spectra, and also evaluated variants of uncertain significance, including the
      MUTYH p.Gln338His mutation. Moreover this study underscores the phenotypic
      heterogeneity and genotype-phenotype correlations in a cohort of Italian
      patients.

PMID- 27705016
TI  - A&E waits online.
AB  - Lincoln County Hospital's emergency department has installed a webcam so that
      people with minor injuries can check from home how long they may have to wait for
      treatment.

PMID- 27705018
TI  - Emergency staff in flu pandemic training DVD.
AB  - Healthcare professionals across the UK could learn how to manage a flu pandemic
      better thanks to A&E staff at North Manchester General Hospital and Leicester
      Royal Infirmary.

PMID- 27705017
TI  - NICE issues guidance on urinary tract infection.
AB  - The National Institute for Health and Clinical Excellence last month issued
      guidance on diagnosing and managing urinary tract infection (UTI) in children.

PMID- 27705020
TI  - Obese patient.
AB  - With the ongoing increase in the incidence of obesity, there is some evidence to
      suggest that inadequacy of equipment impairs the care of obese patients.

PMID- 27705019
TI  - ?
AB  - Bite size: nurses at NHS Direct say they have been swamped with calls from
      patients who have been bitten by mosquitoes this summer. There were 1,491 calls
      to the service in the first 12 days of August, 28 per cent higher than in the
      same period last year. The increase is attributed to the large amounts of still
      water that resulted from the heavy rain.

PMID- 27705021
TI  - College 'virtual entity' plan for ECA shelved.
AB  - Controversial plans to replace the RCN Emergency Care Association (ECA) and other
      college forums with 'virtual entities' and local networks have been shelved
      following widespread criticism.

PMID- 27705022
TI  - Screening for 'hazardous drinkers'.
AB  - A survey of all emergency departments (EDs) in England has found that only four
      out of 191 formally assess the 'hazardous drinking' of patients.

PMID- 27705023
TI  - Collaborative practice.
AB  - This study aims to identify a model of collborative practice, as well as
      incidences of collaboration or hindrances, for out-of-hospital unscheduled care
      and other relevant fields. The authors involved a range of emergency care
      practitioners (ECPs), including paramedics and nurses, employed by an ambulance
      service.

PMID- 27705024
TI  - Cruise control.
AB  - 'I 'd rather have three hours on a beach in Barbados than a week in
      Wolverhampton,' says nurse Andrea Brown, comparing her previous life in the
      English midlands to the dream she lives today. Ms Brown has found a way to mix
      her wanderlust with her love of emergency care by getting a job as a nurse on a
      luxury cruise ship. Her current tour of duty is on the opulent Cunard liner,
      Queen Mary 2 (QM2), which she has been aboard for several months.

PMID- 27705025
TI  - Paediatric care: then and now.
AB  - It's been more than ten years since we became emergency nurses and, in this time,
      emergency care provision for children has changed considerably.

PMID- 27705026
TI  - Hydrogels with smart systems for delivery of hydrophobic drugs.
AB  - INTRODUCTION: Smart hydrogel systems present opportunities to not only provide
      hydrophobic molecule encapsulation capability but to also respond to specific
      delivery routes. Areas covered: An overview of the design principles, preparation
      methods and applications of hydrogel systems for delivery of hydrophobic drugs is
      given. It begins with a summary of the advantages of hydrogels as delivery
      vehicles over other approaches, particularly macromolecular nanocarriers, before
      proceeding to address the design and preparation strategies and chemistry
      involved, with a particular focus on the introduction of hydrophobic domains into
      (naturally) hydrophilic hydrogels. Finally, the applications in different
      delivery routes are discussed. Expert opinion: Modifications to conventional
      hydrogels can endow them with the capability to carry hydrophobic drugs but other
      functions as well, such as the improved mechanical stability, which is important
      for long-term in vivo residence and/or self-healing properties useful for
      injectable delivery pathways. These modifications harness hydrophobic-hydrophobic
      forces, physical interactions and inclusion complexes. The lack of in-depth
      understanding of these interactions, currently limits more delicate and
      application-oriented designs. Increased efforts are needed in (i) understanding
      the interplay of gel formation and simultaneous drug loading; (ii) improving
      hydrogel systems with respect to their biosafety; and (iii) control over release
      mechanism and profile.

PMID- 27705027
TI  - Lessons to be learned from serum biomarkers in psoriasis and IBD - the potential
      role in SpA.
AB  - INTRODUCTION: Early diagnosis, monitoring of disease activity, prediction of
      treatment response, and structural outcome remain major challenges in
      spondyloarthritis (SpA). Biomarkers could play a role in addressing these
      challenges, but in SpA there is a lack of suitable biomarkers. Areas covered: As
      SpA is clinically and pathophysiologically closely related to psoriasis and
      inflammatory bowel disease (IBD), we reviewed in literature, the value of serum
      biomarkers in these conditions with the aim to find potential candidates for
      assessing SpA. Expert commentary: Candidates of interest were antimicrobial
      peptides, including serum human beta defensin-2 (hBD-2) and lipocalin-2 (LCN-2),
      and class-1 MHC molecule beta2-microglobulin. Since these biomarkers are relevant
      in psoriasis and/or IBD from a pathophysiological point of view, and may play a
      role in the pathogenesis of SpA, we recommend further exploration of their value
      as biomarker in the diagnosis and prognosis of SpA.

PMID- 27705028
TI  - Type 2 diabetes and metabolic syndrome - adipokine levels and effect of drugs.
AB  - Type 2 diabetes mellitus (T2DM) is a consequence of complex interactions among
      multiple genetic variants and environmental risk factors. This complex disorder
      is also characterized by changes in various adipokines. In this study, our
      objective was to estimate the levels of adiponectin, leptin, and resistin (ALR)
      in T2DM patients, besides studying the effect of various drugs on their levels.
      Study participants included 400 diabetic and 300 normal patients from the
      Department of Endocrinology and Department of Biochemistry, Govt Medical College
      Srinagar. Subjects were categorized under various groups, i.e., Group 1
      (metformin treated) and Group 2 (glimepiride treated), and cases were also
      categorized as obese with T2DM (Group A), obese without T2DM (Group B), and T2DM
      only (Group C). The serum ALR levels were estimated by ELISA (Alere), and
      biochemical parameters were also evaluated before and after treatment.
      Adiponectin levels were found to be significantly lower in T2DM cases as compared
      to controls (12 +/- 5.5 versus 22.5 +/- 7.9 MUg/ml), while leptin and resistin
      levels were found to be significantly higher than controls (14.3 +/- 7.4 versus
      7.36 +/- 3.73 ng/ml) (13.4 +/- 1.56 versus 7.236 +/- 2.129 pg/ml). Taking the
      effect of drugs into consideration, the effect on adiponectin and resistin levels
      was found to be highly significant in Group 2 before and after treatment (11 +/-
      5 versus 19.2 +/- 4.5 MUg/ml) (13.6 +/- 2.5 versus 7.3 +/- 2.9 pg/ml), while more
      effect was observed in leptin among Group 1 (metformin)-treated cases (27 +/- 15
      ng/ml versus 15 +/- 15 ng/ml). Further the adiponectin levels were found to be
      significantly lower in Group B, while leptin and resistin levels were found to be
      significantly higher among obese cases when compared to T2DM cases only.
      Glimepiride also shows more effect on FBG, HbA1c% levels, while metformin shows
      more effect on Lipid profile levels. From the study, it can be concluded that ALR
      levels are affected by use of antidiabetic drugs among which glimepiride shows
      more effect on adiponectin and resistin levels, while leptin gets affected more
      by metformin. It can also be proposed that ALR levels are not affected by
      diabetes only, suggesting that their alterations in T2DM may be due to obesity as
      we observed more ALR changes in obese cases when compared to T2DM cases, and so
      there might be an important link between adiposity and insulin resistance.

PMID- 27705029
TI  - Patient safety competence for final-year health professional students:
      Perceptions of effectiveness of an interprofessional education course.
AB  - As final-year medical and nursing students will soon play key roles in frontline
      patient care, their preparedness for safe, reliable care provision is of special
      importance. We assessed patient safety competencies of final-year health
      profession students, and the effect of a 1-day patient safety education programme
      on these competencies. A cross-sectional survey was conducted with 233 students
      in three colleges of medicine, nursing, and traditional medicine in Seoul. A
      before-and-after study followed to evaluate the effectiveness of the curriculum.
      Patient safety competency was measured using the Health-Professional Education
      for Patients Safety Survey (H-PEPSS) and an objective patient safety knowledge
      test. The mean scores were 3.4 and 1.7 out of 5.0, respectively. The
      communication domain was rated the highest and the teamwork domain was rated the
      lowest. H-PEPSS scores significantly differed between the students from three
      colleges. The 1-day patient safety education curriculum significantly improved H
      PEPSS and knowledge test scores. These results indicated that strengthening
      patient safety competencies, especially teamwork, of students is required in
      undergraduate healthcare curricula. A 1-day interprofessional patient safety
      education programme may be a promising strategy. The findings suggest that
      interprofessional patient safety education needs to be implemented as a core
      undergraduate course to improve students' safety competence.

PMID- 27705030
TI  - Staff perceptions of collaboration on a new interprofessional unit using the
      Assessment of Interprofessional Team Collaboration Scale (AITCS).
AB  - The aim of this study was to obtain baseline information on staff attitudes and
      perceptions of interprofessional collaboration on a newly formed
      interprofessional education unit. The Assessment of Interprofessional Team
      Collaboration Scale (AITCS) was administered to 54 interprofessional team members
      on a 30-bed medical interprofessional education (IPE) unit. We found that the
      team members respected each other but felt they needed more organisational
      support to further develop team skills. Additionally, team members noted that
      they did not have enough time for team reflection or to make changes to the team
      processes. The results obtained from this study will help to develop and refine
      educational strategies to assist the staff working on the IPE unit.

PMID- 27705031
TI  - A short-term cost-utility analysis of insulin degludec versus insulin glargine
      U100 in patients with type 1 or type 2 diabetes in Denmark.
AB  - BACKGROUND AND AIMS: Insulin degludec is an insulin analog with an ultra-long
      duration of action that exhibits less intra-patient variability in its glucose
      lowering activity, and reduces nocturnal, overall, and severe hypoglycemia
      relative to insulin glargine. The aim of the present study was to evaluate the
      cost-effectiveness of insulin degludec relative to insulin glargine in patients
      with: type 1 diabetes (T1D), type 2 diabetes receiving basal-only therapy
      (T2DBOT), and type 2 diabetes receiving basal-bolus therapy (T2DBB) in Denmark.
      METHODS: A short-term (1 year) cost-utility model was developed to model insulin
      use, non-severe and severe hypoglycemia, and self-monitoring of blood glucose in
      patients using insulin degludec and insulin glargine from the perspective of a
      Danish healthcare payer. Where possible, data were derived from Danish patients
      with diabetes and meta-analyses of clinical trials comparing insulin degludec
      with insulin glargine. Using these characteristics, the model estimated costs and
      quality-adjusted life years (QALYs) gained for the two insulin regimens in each
      of the three diabetes populations. RESULTS: Insulin degludec dominated insulin
      glargine (i.e. reduced costs while improving quality-adjusted life expectancy) in
      patients with T1D and patients with type 2 diabetes using a basal-only insulin
      regimen. In the T2DBB cohort, insulin degludec was associated with an incremental
      cost-effectiveness ratio of DKK 221,063 per QALY gained, which would be
      considered cost-effective at a willingness-to-pay threshold of EUR 30,000 (~DKK
      224,000) per QALY gained. Sensitivity analysis showed that results were most
      affected by changes in hypoglycemia rate ratio assumptions, but were broadly
      insensitive to changes in individual input parameters. CONCLUSIONS: Insulin
      degludec reduces incidence of hypoglycemia and improves quality-of-life in
      patients with diabetes. Over a 1-year time horizon, insulin degludec resulted in
      cost savings relative to insulin glargine in T1D and T2DBOT cohorts, while being
      cost-effective in T2DBB.

PMID- 27705032
TI  - Intonation patterns in older children with cerebral palsy before and after speech
      intervention.
AB  - PURPOSE: This paper examined the production of intonation patterns in children
      with developmental dysarthria associated with cerebral palsy (CP) prior to and
      after speech intervention focussing on respiration and phonation. The study
      further sought to establish whether intonation performance might be related to
      changes in speech intelligibility. METHOD: Intonation patterns were examined
      using connected speech samples of 15 older children with moderate to severe
      developmental dysarthria due to CP (9 females; age range: 11-18). Recordings were
      made prior to and after speech intervention based on a systems approach. Analyses
      are focussed on the use of intonation patterns, pitch accentuation and phrasing.
      RESULT: Group analyses showed a significant increase in the use of rising
      intonation patterns after intervention. There were also some indications that
      this increase might have been related to gains in speech intelligibility for some
      of the children. No changes were observed regarding pitch accentuation and
      phrasing following intervention. CONCLUSION: The findings highlight that changes
      can occur in the use of intonation patterns in children with dysarthria and CP
      following speech systems intervention. It is hypothesised that the emergence of
      the rising pattern in some of the children's intonational inventories possibly
      reflected improved breath support and control of laryngeal muscles.

PMID- 27705033
TI  - Interprofessional education in the Arabic-speaking Middle East: Perspectives of
      pharmacy academics.
AB  - The current status of interprofessional education (IPE) in Arabic Middle Eastern
      countries is largely unexamined and there is a need to assess IPE and
      collaborative practice in these countries. As faculty attitudes towards IPE are
      believed to be one of the main factors that affect the successful integration of
      IPE into the different healthcare curricula, this article aims to explore the
      attitudes and views of pharmacy academics in Arabic-speaking Middle Eastern
      countries towards IPE and collaborative practice. The findings from this article
      are part of a larger study investigating pharmacy's perspectives of IPE and
      collaborative practice in Qatar and the Middle East. An online survey which
      included three validated scales was used to gather information from pharmacy
      academics at 89 pharmacy schools in 14 countries. The response rate was 107 out
      of 334 (32%) and the majority of the respondents were from Jordan, Qatar,
      Lebanon, and Saudi Arabia. Statistical analysis was completed descriptively as
      well as inferentially using a series of independent t-tests. Overall pharmacy
      academics had positive attitudes towards IPE. The majority of the respondents,
      90.8% (n = 99), perceived IPE to be important. Age, likelihood to engage in IPE,
      and years of IPE experience were the factors that were related to faculty
      members' attitudes towards IPE. Highly perceived barriers for implementing IPE
      included cultural challenges for each profession, scheduling common courses, and
      activities in addition to limited resources. The study findings indicated that
      pharmacy academics in the Middle East are ready to pursue IPE. These results can
      serve as impetus for implementing IPE in Middle Eastern countries.

PMID- 27705034
TI  - The High-Pull Exercise: A Comparison Between a VersaPulley Flywheel Device and
      the Free Weight.
AB  - The aim of this study was to examine the kinematics and kinetics (force,
      velocity, and acceleration) and blood lactate concentration with the VersaPulley
      (VP) device in comparison with free-weight (FW) exercise at a similar external
      load. Fifteen rugby players randomly performed 2 training sessions of 6 sets of 6
      repetitions with 20 s of recovery between sets of the high-pull exercise with the
      VP and the FW. The training sessions were separated by 72 h. Barbell displacement
      (cm), peak velocity (m/s), peak acceleration (m/s2), mean propulsive velocity
      (m/s), mean propulsive acceleration (m/s2), propulsive phase (%), and mean and
      maximal force (N) were continuously recorded during each repetition. Blood
      lactate concentration was measured after each training session (end) and 3 min
      and 5 min later. Barbell displacement (+4.8%, small ES), peak velocity (+4.5%
      small ES), mean propulsive acceleration (+8.8%, small ES), and eccentric force
      (+26.7, large ES) were substantially higher with VP than with FW. Blood lactate
      concentration was also greater after the VP exercise (end +32.9%, 3 min later
      +36%, 5 min later +33.8%; large ES). Maximal concentric force was substantially
      higher with FW than VP during the 6th set (+6.4%, small ES). In the cohort and
      exercise investigated in the current study, VP training can be considered an
      efficient training device to induce an accentuated eccentric overload and
      augmented metabolic demands (ie, blood lactate concentration).

PMID- 27705035
TI  - Nurses asked to tackle domestic violence.
AB  - Emergency nurses across the UK are being called on to help draw up government
      guidelines on detecting and managing patients who are affected by domestic
      violence.

PMID- 27705036
TI  - ?
AB  - Birds of a feather: emergency nurse Michelle Young and Claudine Roche are
      entering the Flora London Marathon this month dressed in costumes inspired by the
      cartoon character, Road Runner. They will be running for the charity, Sense,
      which supports people with deafblindness, a combination of both sight and hearing
      difficulties. Ms Roche, who works with Ms Young in the A&E department at St
      Thomas' Hospital, London, says: 'I want to run for Sense because I was lucky
      enough to be born with my five senses and take it for granted. I want to raise
      cash for people who don't have that privilege.' To find out more about sponsoring
      Ms Roche and Ms Young, log on to www.justgiving.com/roadrunner-claude.

PMID- 27705037
TI  - Ambulatory care guidance a 'missed opportunity'.
AB  - Official guidance to help transform the delivery of emergency care for adults has
      been described a 'missed opportunity'.

PMID- 27705038
TI  - Drug errors.
AB  - Registered nurses are expected to know about the drugs they administer, their
      indications, contraindications and adverse effects, and their correct doses. In
      addition to this, most registered nurses can rattle off the correct procedures
      for safe drug administration.

PMID- 27705039
TI  - Forensic nurse group launched.
AB  - An association has been set up to bring together forensic nurses from across the
      UK and improve conviction rates for sexual offenders.

PMID- 27705040
TI  - 'Off the mark'.
AB  - I write to express my concern at the views expressed by Claire Picton in her
      editorial of the March issue of Emergency Nurse. Frankly, I believe that her
      comments are way off the mark.

PMID- 27705041
TI  - Direct to the top.
AB  - NHS Direct has announced the appointment of Matt Tee as i ts new chief executive.
      Mr Tee is currently director general of communications at the Department of
      Health and takes up post next month.

PMID- 27705042
TI  - A unique role?
AB  - I am pleased to see that the seeds I sowed at the RCN Emergency Care Association
      conference last year are now beginning to develop and that Clare Picton's
      editorial in the March issue of Emergency Nurse has brought my questions to a
      wider audience.

PMID- 27705044
TI  - X-rays re-examined.
AB  - Revised guidance on requesting X-ray and other images is to be published this
      summer following advice from the RCN Emergency Care Association.

PMID- 27705043
TI  - A common sense approach to IT.
AB  - As many of us know, information technology (IT) can be both a wonder and a
      disaster. The challenge for the NHS is to avoid the disasters while harnessing
      the wonders to benefit patient care.

PMID- 27705045
TI  - ?
AB  - Breathe easy: to mark World Asthma Day on May 1, Asthma UK is launching an
      emergency asthma care resource for healthcare professionals. The materials show
      the process of care from when someone with asthma first presents, through to
      their follow-up arrangements and return home. The resource contains guidance on
      evidence based standards of emergency asthma care, no matter where care is
      provided, templates to adapt to individual settings, training slides and patient
      information booklets. It will be sent to around 20,000 key healthcare
      professionals, including A&E and ambulance staff, across the UK, but it will also
      be available to download from www.asthma.org.uk.

PMID- 27705046
TI  - Oxygen delivery.
AB  - The authors of this short study set out to determine the baseline knowledge of
      oxygen prescription and delivery in senior house officers (SHOs) about to start
      work in emergency departments (EDs).

PMID- 27705047
TI  - Board's eye view.
AB  - The NHS is seldom out of the news headlines these days, but rarely to report
      excellence in care. Instead, the news is usually of ward closures, or of threats
      to close emergency departments and other essential services.

PMID- 27705048
TI  - Venepuncture.
AB  - Venepuncture is one of the most commonly performed invasive clinical procedures,
      and is performed on millions of people worldwide. Complications, which can
      include neurovascular injuries, are extremely rare.

PMID- 27705049
TI  - New poly(ester-amide) copolymers modified with polyether (PEAE) for anticancer
      drug encapsulation.
AB  - New poly(ester-amide) copolymers modified with polyethers were developed for
      carboplatin encapsulation. These new copolymers contain hydrophobic blocks made
      of tyrosine derivative and dimer fatty acid, and poly(ethylene glycol) (PEG) as
      hydrophilic blocks. Short-term hydrolytic degradation revealed high water
      absorption, slight increase of pH of simulated body fluid and change of sample
      shape, which indicated the erosive mechanism of polymers degradation. Poly(ester
      amide)-PEG copolymers were used for microspheres preparation and carboplatin
      encapsulation. A double emulsification process was used to produce microspheres
      with an average diameter of 20-30 MUm. It was found that the amount of drug
      released was controlled by the molecular mass of PEG used for microspheres
      preparation. Mathematical models were used to elucidate the release mechanism of
      the carboplatin from the microspheres. The results demonstrate that poly(ester
      amide)-PEG copolymers may be used for targeted carboplatin encapsulation and
      release.

PMID- 27705050
TI  - The Effect of Backpack Carriage on the Biomechanics of Walking: A Systematic
      Review and Preliminary Meta-Analysis.
AB  - The aim of this systematic review was to evaluate the impact of bilaterally
      symmetrical backpack systems borne on the posterior trunk on walking
      biomechanics, as backpacks represent the most prevalent method of load carriage
      in the military and civilian population. A search of electronic databases was
      performed for studies that only investigated posteriorly-borne backpack carriage
      during level-grade walking (treadmill and over ground). Methodology of studies
      was assessed, and both meta-analysis and qualitative synthesis were completed.
      Fifty-four studies were included in this review. In summary, the available
      literature showed that backpack carriage in walking was associated with an
      increased trunk flexion angle, increased hip and ankle range of motion, increased
      vertical and horizontal ground reaction force, increased cadence, and reduced
      stride length. Several variations in backpack carriage protocols could explain
      between-study variations in results, including: walking speed, backpack carriage
      skill level, the use of a hip belt, and posterior displacement of the load away
      from the trunk. The findings of this systematic review will inform backpack
      carriage practices in the area of injury risk assessment and physical performance
      enhancement.

PMID- 27705051
TI  - RNA-binding proteins are a major target of silica nanoparticles in cell extracts.
AB  - Upon contact with biological fluids, nanoparticles (NPs) are readily coated by
      cellular compounds, particularly proteins, which are determining factors for the
      localization and toxicity of NPs in the organism. Here, we improved a
      methodological approach to identify proteins that adsorb on silica NPs with high
      affinity. Using large-scale proteomics and mixtures of soluble proteins prepared
      either from yeast cells or from alveolar human cells, we observed that proteins
      with large unstructured region(s) are more prone to bind on silica NPs. These
      disordered regions provide flexibility to proteins, a property that promotes
      their adsorption. The statistical analyses also pointed to a marked
      overrepresentation of RNA-binding proteins (RBPs) and of translation initiation
      factors among the adsorbed proteins. We propose that silica surfaces, which are
      mainly composed of Si-O- and Si-OH groups, mimic ribose-phosphate molecules (rich
      in -O- and -OH) and trap the proteins able to interact with ribose-phosphate
      containing molecules. Finally, using an in vitro assay, we showed that the
      sequestration of translation initiation factors by silica NPs results in an
      inhibition of the in vitro translational activity. This result demonstrates that
      characterizing the protein corona of various NPs would be a relevant approach to
      predict their potential toxicological effects.

PMID- 27705053
TI  - Electrochemotherapy of mucosal head and neck tumors: a systematic review.
AB  - BACKGROUND: Electrochemotherapy, the combination of electroporation and
      chemotherapy, is mainly used in the palliative setting for treatment of cutaneous
      and subcutaneous metastases; however, new applications are continuously being
      explored. Patients with head and neck cancer are primarily treated with surgery
      and/or radio-chemotherapy. In the setting of local recurrence with no further
      curative treatment options available, electrochemotherapy could be of value. We
      therefore performed a systematic search of the present literature. MATERIALS AND
      METHODS: Eligible studies presented data from patients with head and neck cancer
      treated across the mucosal surface with electrochemotherapy. The search resulted
      in 11 studies with a total of 72 patients. RESULTS: Overall complete response was
      reported as good, especially in primary small tumors. Side effects were minor in
      primary tumors whereas large, recurrent tumors displayed more frequent side
      effects and some serious adverse events. Design and structure of the studies
      differed considerably, making general comparisons difficult. CONCLUSION: Few
      studies concerning electrochemotherapy on mucosal head and neck tumors are
      available and they are not easily comparable. Overall response to treatment is
      good; nonetheless, further systematic studies are warranted.

PMID- 27705052
TI  - RENEB biodosimetry intercomparison analyzing translocations by FISH.
AB  - PURPOSE: In the framework of RENEB, several biodosimetry exercises were conducted
      analyzing different endpoints. Among them, the analysis of translocations is
      considered the most useful method for retrospective biodosimetry due to the
      relative stability of their frequency with post irradiation time. The aim of this
      study was to harmonize the accuracy of translocation-based biodosimetry within
      the RENEB consortium. MATERIALS AND METHODS: An initial telescoring exercise
      analyzing FISH metaphase images was done to harmonize chromosome aberration
      descriptions. Then two blind intercomparison exercises (IE) were performed, by
      sending irradiated blood samples to each partner. Samples were cultured and
      stained by each partner using their standard protocol and translocation frequency
      was used to produce dose estimates. RESULTS: The coefficient of variation in the
      1st IE (CV = 0.34) was higher than in the 2nd IE (CV = 0.16 and 0.23 in the two
      samples analyzed), for the genomic frequency of total translocations. Z-score
      analysis revealed that eight out of 10 and 17 out of 20 dose estimates were
      satisfactory in the 1st and 2nd IE, respectively. CONCLUSIONS: The results
      obtained indicate that, despite the problems identified in few partners, which
      can be corrected, the RENEB consortium is able to carry out retrospective
      biodosimetry analyzing the frequency of translocations by FISH.

PMID- 27705054
TI  - Enhancement of radiosensitivity of melanoma cells by pegylated gold nanoparticles
      under irradiation of megavoltage electrons.
AB  - PURPOSE: Gold nanoparticles (GNP) have significant potential as radiosensitizer
      agents due to their distinctive properties. Several studies have shown that the
      surface modification of nanoparticles with methyl polyethylene glycol (mPEG) can
      increase their biocompatibility. However, the present study investigated the
      radiosensitization effects of mPEG-coated GNP (mPEG-GNP) in B16F10 murine
      melanoma cells under irradiation of 6 MeV Electron beam. MATERIALS AND METHODS:
      The synthesized GNP were characterized by UV-Visible spectroscopy, dynamic light
      scattering, transmission electron microscopy, and zeta potential. Enhancement of
      radiosensitization was evaluated by the clonogenic assay at different radiation
      doses of megavoltage electron beams. RESULTS: It was observed that mPEG-GNP with
      a hydrodynamic size of approximately 50 nm are almost spherical and cellular
      uptake occurred at all concentrations. Both proliferation efficiency and survival
      fraction decreased with increasing mPEG-GNP concentration. Furthermore,
      significant GNP sensitization occurred with a maximum dose enhancement factor of
      1.22 at a concentration of 30 MUM. CONCLUSIONS: Pegylated-GNP are taken up by
      B16F10 cancer cells and cause radiosensitization in the presence of 6 MeV
      electrons. The radiosensitization effects of GNP may probably be due to
      biological processes. Therefore, the underlying biological mechanisms beyond the
      physical dose enhancement need to be further clarified.

PMID- 27705055
TI  - A Comparison of Vertical Stiffness Values Calculated from Different Measures of
      Center of Mass Displacement in Single-Leg Hopping.
AB  - This study assessed the agreement between Kvert calculated from 4 different
      methods of estimating vertical displacement of the center of mass (COM) during
      single-leg hopping. Healthy participants (N = 38) completed a 10-s single-leg
      hopping effort on a force plate, with 3D motion of the lower limb, pelvis, and
      trunk captured. Derived variables were calculated for a total of 753 hop cycles
      using 4 methods, including: double integration of the vertical ground reaction
      force, law of falling bodies, a marker cluster on the sacrum, and a segmental
      analysis method. Bland-Altman plots demonstrated that Kvert calculated using
      segmental analysis and double integration methods have a relatively small bias
      (0.93 kN?m-1) and 95% limits of agreement (-1.89 to 3.75 kN?m-1). In contrast, a
      greater bias was revealed between sacral marker cluster and segmental analysis (
      2.32 kN?m-1), sacral marker cluster and double integration (-3.25 kN?m-1), and
      the law of falling bodies compared with all methods (17.26-20.52 kN?m-1). These
      findings suggest the segmental analysis and double integration methods can be
      used interchangeably for the calculation of Kvert during single-leg hopping. The
      authors propose the segmental analysis method to be considered the gold standard
      for the calculation of Kvert during single-leg, on-the-spot hopping.

PMID- 27705057
TI  - Reliability and Validity of Quantitative Video Analysis of Baseball Pitching
      Motion.
AB  - Video recordings are used to quantitatively analyze pitchers' techniques.
      However, reliability and validity of such analysis is unknown. The purpose of the
      study was to investigate the reliability and validity of joint and segment angles
      identified during a pitching motion using video analysis. Thirty high school
      baseball pitchers participated. The pitching motion was captured using 2 high
      speed video cameras and a motion capture system. Two raters reviewed the videos
      to digitize the body segments to calculate 2-dimensional angles. The
      corresponding 3-dimensional angles were calculated from the motion capture data.
      Intrarater reliability, interrater reliability, and validity of the 2-dimensional
      angles were determined. The intrarater and interrater reliability of the 2
      dimensional angles were high for most variables. The trunk contralateral flexion
      at maximum external rotation was the only variable with high validity. Trunk
      contralateral flexion at ball release, trunk forward flexion at foot contact and
      ball release, shoulder elevation angle at foot contact, and maximum shoulder
      external rotation had moderate validity. Two-dimensional angles at the shoulder,
      elbow, and trunk could be measured with high reliability. However, the angles are
      not necessarily anatomically correct, and thus use of quantitative video analysis
      should be limited to angles that can be measured with good validity.

PMID- 27705056
TI  - In Vivo Kinematics of Healthy and Osteoarthritic Knees During Stepping Using
      Density-Based Image-Matching Techniques.
AB  - The purpose of this study was to investigate in vivo kinematics in healthy and
      osteoarthritic (OA) knees during stepping using image-matching techniques. Six
      healthy volunteers and 14 patients with a medial OA knee before undergoing total
      knee arthroplasty performed stepping under periodic anteroposterior radiograph
      images. We analyzed the three-dimensional kinematic parameters of knee joints
      using radiograph images and CT-derived digitally reconstructed radiographs. The
      average extension/flexion angle ranged 6 degrees /53 degrees  and 16 degrees /44
      degrees  in healthy and OA knees, with significant difference in extension (P =
      .02). The average varus angle was -2 degrees  and 6 degrees  in healthy and OA
      knees, with a significant difference (P = .03). OA knees showed 1.7 degrees  of
      significantly larger varus thrust (P = .04) and 4.2 mm of significantly smaller
      posterior femoral rollback (P = .04) compared with healthy knees. Coronal limb
      alignment in OA knees significantly correlated with varus thrust (R2 = .36, P =
      .02) and medial shift of the femur (R2 = .34, P = .03). Both normal and OA knees
      showed no transverse plane instability, including anteroposterior, mediolateral
      directions, or axial rotation. In conclusion, OA knees demonstrated different
      kinematics during stepping from normal knees: less knee extension, larger varus
      thrust, less posterior translation, and larger medial shift.

PMID- 27705058
TI  - Estimates of Running Ground Reaction Force Parameters from Motion Analysis.
AB  - We compared running mechanics parameters determined from ground reaction force
      (GRF) measurements with estimated forces obtained from double differentiation of
      kinematic (K) data from motion analysis in a broad spectrum of running speeds
      (1.94-5.56 m?s-1). Data were collected through a force-instrumented treadmill and
      compared at different sampling frequencies (900 and 300 Hz for GRF, 300 and 100
      Hz for K). Vertical force peak, shape, and impulse were similar between K methods
      and GRF. Contact time, flight time, and vertical stiffness (kvert) obtained from
      K showed the same trend as GRF with differences < 5%, whereas leg stiffness
      (kleg) was not correctly computed by kinematics. The results revealed that the
      main vertical GRF parameters can be computed by the double differentiation of the
      body center of mass properly calculated by motion analysis. The present model
      provides an alternative accessible method for determining temporal and kinetic
      parameters of running without an instrumented treadmill.

PMID- 27705059
TI  - Accuracy of a Wearable Sensor for Measures of Head Kinematics and Calculation of
      Brain Tissue Strain.
AB  - Wearable kinematic sensors can be used to study head injury biomechanics based on
      kinematics and, more recently, based on tissue strain metrics using kinematics
      driven brain models. These sensors require in-situ calibration and there is
      currently no data conveying wearable ability to estimate tissue strain. We
      simulated head impact (n = 871) to a 50th percentile Hybrid III (H-III) head
      wearing a hockey helmet instrumented with wearable GForceTracker (GFT) sensors
      measuring linear acceleration and angular velocity. A GFT was also fixed within
      the H-III head to establish a lower boundary on systematic errors. We quantified
      GFT errors relative to H-III measures based on peak kinematics and cumulative
      strain damage measure (CSDM). The smallest mean errors were 12% (peak resultant
      linear acceleration) and 15% (peak resultant angular velocity) for the GFT within
      the H-III. Errors for GFTs on the helmet were on average 54% (peak resultant
      linear acceleration) and 21% (peak resultant angular velocity). On average, the
      GFT inside the helmet overestimated CSDM by 0.15.

PMID- 27705060
TI  - Effective Propulsion in Swimming: Grasping the Hydrodynamics of Hand and Arm
      Movements.
AB  - In this paper, a literature review is presented regarding the hydrodynamic
      effects of different hand and arm movements during swimming with the aim to
      identify lacunae in current methods and knowledge, and to distil practical
      guidelines for coaches and swimmers seeking to increase swimming speed.
      Experimental and numerical studies are discussed, examining the effects of hand
      orientation, thumb position, finger spread, sculling movements, and hand
      accelerations during swimming, as well as unsteady properties of vortices due to
      changes in hand orientation. Collectively, the findings indicate that swimming
      speed may be increased by avoiding excessive sculling movements and by spreading
      the fingers slightly. In addition, it appears that accelerating the hands rather
      than moving them at constant speed may be beneficial, and that (in front crawl
      swimming) the thumb should be abducted during entry, catch, and upsweep, and
      adducted during the pull phase. Further experimental and numerical research is
      required to confirm these suggestions and to elucidate their hydrodynamic
      underpinnings and identify optimal propulsion techniques. To this end, it is
      necessary that the dynamical motion and resulting unsteady effects are accounted
      for, and that flow visualization techniques, force measurements, and simulations
      are combined in studying those effects.

PMID- 27705061
TI  - Errors in Shoulder Joint Position Sense Mainly Come from the Glenohumeral Joint.
AB  - While synchronous movement of the glenohumeral and scapulothoracic joints has
      been emphasized in previous kinematics studies, most investigations of shoulder
      joint position sense have treated the shoulder complex as a single joint. The
      purposes of this study were to investigate the joint position sense errors of the
      humerothoracic, glenohumeral, and scapulothoracic joints at different elevation
      angles and to examine whether the errors of the glenohumeral and scapulothoracic
      joints contribute to the errors of the humerothoracic joint. Fifty-one subjects
      with healthy shoulders were recruited. Active joint position sense of the
      humerothoracic, glenohumeral, and scapulothoracic joints was measured at 50
      degrees , 70 degrees , and 90 degrees  of humerothoracic elevation in the
      scapular plane. The results showed that while scapulothoracic joint position
      sense errors were not affected by target angles, there was an angle effect on
      humerothoracic and glenohumeral errors, with errors decreasing as the target
      angles approached 90 degrees  of elevation. The results of a multiple regression
      analysis revealed that glenohumeral errors explained most of the variance of the
      humerothoracic errors and that scapulothoracic errors had a weaker predictive
      relationship with humerothoracic errors. Therefore, it may be necessary to test
      scapular joint position sense separately in addition to the assessment of the
      overall shoulder joint position sense.

PMID- 27705062
TI  - Decoupling the Wrist: A Cadaveric Experiment Examining Wrist Kinematics Following
      Midcarpal Fusion and Scaphoid Excision.
AB  - At the wrist, kinematic coupling (the relationship between flexion-extension and
      radial-ulnar deviation) facilitates function. Although the midcarpal joint is
      critical for kinematic coupling, many surgeries, such as 4-corner fusion (4CF)
      and scaphoidexcision 4-corner fusion (SE4CF), modify the midcarpal joint. This
      study examines how 4CF and SE4CF influence kinematic coupling by quantifying
      wrist axes of rotation. Wrist axes of rotation were quantified in 8 cadaveric
      specimens using an optimization algorithm, which fit a 2-revolute joint model to
      experimental data. In each specimen, data measuring the motion of the third
      metacarpal relative to the radius was collected for 3 conditions (nonimpaired,
      4CF, SE4CF). The calculated axes of rotation were compared using spherical
      statistics. The angle between the axes of rotation was used to assess coupling,
      as the nonimpaired wrist has skew axes (ie, angle between axes approximately 60
      degrees ). Following 4CF and SE4CF, the axes are closer to orthogonal than those
      of the nonimpaired wrist. The mean angle (+/-95% confidence interval) between the
      axes was 92.6 degrees  +/- 25.2 degrees  and 99.8 degrees  +/- 22.0 degrees  for
      4CF and SE4CF, respectively. The axes of rotation defined in this study can be
      used to define joint models, which will facilitate more accurate computational
      and experimental studies of these procedures.

PMID- 27705063
TI  - A Comparison of Body Segment Inertial Parameter Estimation Methods and Joint
      Moment and Power Calculations During a Drop Vertical Jump in Collegiate Female
      Soccer Players.
AB  - Athletic individuals may differ in body segment inertial parameter (BSIP)
      estimates due to differences in body composition, and this may influence
      calculation of joint kinetics. The purposes of this study were to (1) compare
      BSIPs predicted by the method introduced by de Leva1 with DXA-derived BSIPs in
      collegiate female soccer players, and (2) examine the effects of these BSIP
      estimation methods on joint moment and power calculations during a drop vertical
      jump (DVJ). Twenty female NCAA Division I soccer players were recruited. BSIPs of
      the shank and thigh (mass, COM location, and radius of gyration) were determined
      using de Leva's method and analysis of whole-body DXA scans. These estimates were
      used to determine peak knee joint moments and power during the DVJ. Compared with
      DXA, de Leva's method located the COM more distally in the shank (P = .008) and
      more proximally in the thigh (P < .001), and the radius of gyration of the thigh
      to be further from the thigh COM (P < .001). All knee joint moment and power
      measures were similar between methods. These findings suggest that BSIP
      estimation may vary between methods, but the impact on joint moment calculations
      during a dynamic task is negligible.

PMID- 27705064
TI  - Age-Related Locomotion Characteristics in Association with Balance Function in
      Young, Middle-Aged, and Older Adults.
AB  - The purpose of this study was to examine age-related gait characteristics and
      their associations with balance function in older adults. A total of 51 adult
      volunteers participated. All subjects underwent locomotion analysis using a 3D
      motion analysis and 12-channel dynamic electromyography system. Dynamic balance
      function was assessed by the Berg Balance Scale. Older adults showed a higher
      level of muscle activation than young adults, and there were significant positive
      correlations between increased age and activation of the trunk and thigh muscles
      in the stance and swing phase of the gait cycle. In particular, back extensor
      muscle activity was mostly correlated with the dynamic balance in older adults.
      Thus, back extensor muscle activity in walking may provide a clue for higher
      falling risk in older adults. This study demonstrates that the back extensor
      muscles play very important roles with potential for rehabilitation training to
      improve balance and gait in older adults.

PMID- 27705065
TI  - The Use of Recovery Strategies Among Participants of the BUPA Great North Run: A
      Cross-Sectional Survey.
AB  - OBJECTIVE: To investigate half-marathon runners' frequency of use of recovery
      strategies, perceptions regarding the most beneficial recovery strategy, and
      reasons for using recovery strategies. DESIGN: Cross-sectional survey.
      PARTICIPANTS: 186 participants of the 13.1 mile BUPA Great North Run 2013.
      METHODS: A questionnaire was developed which required participants to indicate
      how frequently they used 12 different recovery strategies, identify which
      recovery strategy they believed to be most beneficial, and rank 6 reasons for
      using recovery strategies in order of importance. Data were analyzed using a
      Friedman nonparametric ANOVA and additional nonparametric tests. RESULTS: All
      participants used recovery strategies. Stretching was the most commonly used
      recovery strategy (P < .001), whereas the use of nutritional supplements was the
      most commonly selected most beneficial recovery strategy. More than 50% of
      respondents indicated that they never used strategies such as kinesio tape (80%),
      hydrotherapy (78%), or ice baths (71%). A significant difference was observed
      between reasons for using recovery strategy (chi2 (5) = 292.29, P < .001).
      Reducing muscle tightness (rank 4.87) and reducing injury (rank 4.35) were the
      most frequently chosen most important reasons for using recovery strategies.
      Minor sex and age differences in the responses were identified. CONCLUSION:
      Recovery strategy usage appears to be widespread among half-marathon runners;
      however, disparities exist between the frequency of use and perceived
      effectiveness of different recovery strategies. Further research in this area is
      needed to facilitate the development of recovery strategy guidelines which are
      both evidence-based and practically relevant.

PMID- 27705066
TI  - Home Exercises Versus On-Site Rehabilitation in the Management of Lateral Elbow
      Tendinopathy: A Critically Appraised Topic.
AB  - Clinical Scenario: Lateral elbow tendinopathy (LE) is a common musculoskeletal
      condition that often results in pain and disability. An array of conservative
      interventions have been shown to improve patient outcomes in outpatient
      rehabilitation clinics. However, with the rise in health care costs, patients and
      rehabilitation specialists have opted to reduce the number of in-house visits and
      focus on home exercise programs (HEPs). As a result, many rehabilitation
      specialists and patients now depend on HEPs as the primary intervention to treat
      LE. Focused Clinical Question: For individuals with LE, is there evidence to
      suggest that HEPs are as effective as traditional on-site rehabilitation for
      reducing pain and disability? Summary of Search, Best Evidence Appraised, and Key
      Findings: The literature was searched for studies comparing HEP to on-site
      rehabilitation in the management of LE. Two clinical controlled trials (CCTs)
      were included. No studies suggested that HEPs demonstrated equal or improved
      outcomes in pain or disability. Both studies concluded that on-site
      rehabilitation services were more effective at reducing pain and disability in
      the short term. More research is needed to compare the cost effectiveness of both
      HEP and on-site rehabilitation. Clinical Bottom Line: Based on 2 CCTs, it can be
      concluded that there is moderate evidence to suggest that patients with LE
      experience decreased pain and disability scores with on-site rehabilitation
      compared to a guided HEP in the short term. The authors could not draw a
      conclusion regarding long-term effects of treatments or cost effectiveness of the
      2 approaches. Strength of Recommendation: Based on the Centre for Evidence Based
      Medicine, there is level B evidence that a HEP only was not as effective as on
      site rehabilitation services in patients with LE.

PMID- 27705067
TI  - Walking Up to One Hour Per Week Maintains Mobility as Older Women Age: Findings
      from an Australian Longitudinal Study.
AB  - The aim of this study was to identify determinants of walking and whether walking
      maintained mobility among women as they transition from their mid-70s to their
      late 80s. We used 12 years of follow-up data (baseline 1999) from the Australian
      Longitudinal Study on Women's Health (n = 10,322). Fifteen determinants of
      walking were included in the analysis and three indicators of mobility.
      Longitudinal data analyses techniques were employed. Thirteen of the 15
      determinants were significant predictors of walking. Women in their mid-70s who
      walked up to 1 hr per week were less likely to experience loss of mobility in
      very old age, including reduced likelihood of using a mobility aid. Hence, older
      women who do no walking should be encouraged to walk to maintain their mobility
      and their independence as they age, particularly women in their 70s and 80s who
      smoke, are overweight, have arthritis, or who have had a recent fall.

PMID- 27705068
TI  - Antiobesity Effects of Salvia plebeia R. Br. Extract in High-Fat Diet-Induced
      Obese Mice.
AB  - This study was designed to investigate the antiobesity effects of Salvia plebeia
      R. Br. ethanolic extracts (SPE) in mice fed high-fat diets (HFD). Male C57BL/6J
      mice were randomly assigned to four groups: normal diet (Chow), high-fat diet
      (HFD, 45% fat), HFD+SPE 200 (200 mg/kg b.w.), and HFD+SPE 400 (400 mg/kg b.w.).
      Extracts were administered orally every day for 8 weeks. Increases in body/fat
      weight and feed efficiency ratio were monitored in all mice. In addition, obesity
      resulting from feeding HFD to the mice was confirmed by the increase of glucose
      level, aspartate transaminase, alanine transaminase, triglyceride (TG), high
      density lipoprotein cholesterol, very low-density lipoprotein-c, leptin, and
      adiponectin in blood. The SPE-treated mice gained less body and
      mesenteric/subcutaneous adipose tissues weights and had lower TG, very low
      density lipoprotein cholesterol, leptin, and glucose level in serum, compared to
      the HFD group. Moreover, histopathological examinations revealed that the size of
      adipocytes in liver and adipose tissue was significantly decreased by SPE,
      compared to the HFD group. The expression of adipogenesis transcription factors
      (e.g., peroxisome proliferator activated receptor gamma and CCAAT/enhancer
      binding protein alpha) and lipogenesis-related target genes (adipocyte fatty acid
      binding protein 2, lipoprotein lipase, fatty acid synthase, and sterol regulatory
      element-binding transcription factor 1c) in HFD-induced obese mice was decreased
      by SPE treatment. These results suggest that SPE attenuates the fat accumulation
      in HFD-induced obese mice by suppressing the expressions of genes related to
      adipogenesis and lipogenesis activity. Therefore, SPE could be developed as a
      potential therapy for reduction of body weight and antiobesity intervention.

PMID- 27705069
TI  - Exercise Test Performance Reveals Evidence of the Cardiorespiratory Fitness
      Hypothesis.
AB  - Positive physiologic and cognitive responses to aerobic exercise have resulted in
      a proposed cardiorespiratory (CR) fitness hypothesis in which fitness gains drive
      changes leading to cognitive benefit. The purpose of this study was to directly
      assess the CR fitness hypothesis. Using data from an aerobic exercise trial, we
      examined individuals who completed cardiopulmonary and cognitive testing at
      baseline and 26 weeks. Change in cognitive test performance was not related to CR
      fitness change (r2 = .06, p = .06). However, in the subset of individuals who
      gave excellent effort during exercise testing, change in cognitive test
      performance was related to CR fitness change (r2 = .33, p < .01). This was
      largely due to change in the cognitive domain of attention (r2 = .36, p < .01).
      The magnitude of change was not explained by duration of exercise. Our findings
      support further investigation of the CR fitness hypothesis and mechanisms by
      which physiologic adaptation may drive cognitive change.

PMID- 27705070
TI  - The Effectiveness of Low-Dye Taping in Reducing Pain Associated With Plantar
      Fasciitis.
AB  - Plantar fasciitis is one of the most common musculoskeletal disorders of the
      foot. Initial treatment of plantar fasciitis is typically conservative and may
      include heel padding, steroid injections, night splinting, calf stretching,
      ultrasound, foot orthoses, and taping. However, while custom foot orthoses are a
      common treatment method for plantar fasciitis, there is often a waiting period of
      a few weeks for them to be manufactured and delivered. Therefore, taping of the
      foot is often used as a temporary treatment to alleviate pain during the initial
      waiting period. Furthermore, taping may also be used as an alternative to foot
      orthoses for patients who may not tolerate the plantar pressures of an orthotic
      or for tight-fitting footwear that may not accommodate insoles. Specifically, the
      low-Dye taping (LDT) technique is one of the most frequently used methods, and
      recent literature has suggested that it may improve pain outcomes. Therefore,
      this critically appraised topic was conducted to determine the extent to which
      current evidence supports the use of LDT to reduce pain in patients with plantar
      fasciitis.

PMID- 27705072
TI  - Acute Effects of Posture Shirts on Rounded-Shoulder and Forward-Head Posture in
      College Students.
AB  - CONTEXT: Rounded-shoulder and forward-head posture can be contributing factors to
      shoulder pain. Corrective techniques such as manual therapy and exercise have
      been shown to improve these altered postures, but there is little evidence that
      corrective garments such as posture shirts can alter posture. OBJECTIVES: To
      determine the acute effects of corrective postureshirt use on rounded-shoulder
      and forward-head posture in asymptomatic college students. DESIGN: Repeated
      measures intervention study with counterbalanced conditions. SETTING: Research
      laboratory. PARTICIPANTS: 24 members of the general student body of a university,
      18-25 y old, with a forward shoulder angle (FSA) >52 degrees  and no history of
      upper-extremity surgery, scoliosis, active shoulder pain, or shoulder pain in the
      previous 3 mo that restricted participation for 3 consecutive days.
      INTERVENTIONS: Photographic posture assessment under a control condition, under a
      sham or treatment condition (counterbalanced), under another control condition,
      and treatment or sham. MAIN OUTCOME MEASURES: FSA and forward head angle (FHA)
      calculated from a lateral photograph. RESULTS: FSA decreased relative to the
      control condition while participants wore the sham shirt (P = .029) but not the
      corrective posture shirt (P = 1.00). FHA was unchanged between groups (P = .371).
      CONCLUSIONS: Application of a corrective posture shirt did not acutely alter FSA
      or FHA, while application of a sham shirt may decrease FSA at rest.

PMID- 27705073
TI  - Big Data and End-of-Life Care: Promise and Peril.

PMID- 27705074
TI  - Effects of the Addition of a Dual Task to a Supervised Physical Exercise Program
      on Older Adults' Cognitive Performance.
AB  - The purpose of this study was to investigate the effects of the addition of a
      dual task to multicomponent training on cognition of active older adults. Eighty
      physically active older adults were divided into an intervention group (IG) and a
      control group (CG). Both groups performed multicomponent training over 12 weeks.
      The IG simultaneously performed exercises and cognitive tasks. The Mini-Mental
      State Examination, the Montreal Cognitive Assessment, and the Clock Drawing Test
      were used for cognitive assessments. The Timed Up and Go Test associated with a
      cognitive task was used for dual-task assessment. Significant interactions were
      not observed between groups in terms of the cognitive variables or the dual-task
      performance. An interaction was observed only for Timed Up and Go Test
      performance, which was better in the CG than in the IG. Active older adults
      showed no improvement in cognition following the addition of the dual task to the
      multicomponent training.

PMID- 27705075
TI  - Electromyography Activation of the Lower-Limb Muscles Adopting a Physioball and
      Elastic Band to Stabilize the Knee Joint During Multiple Sets With Submaximal
      Loads.
AB  - STUDY DESIGN: Crossover design. CONTEXT: Excessive valgus and varus force which
      affected the knee joint during dynamic tasks has been often associated to lower
      extremity injuries. Strategies to increase the resistance against these
      asymmetries (eg, the use of a physioball between the knees or elastic bands
      around the knees) are often applied in rehabilitation and conditioning programs.
      OBJECTIVE: The purpose of this study was to investigate the effect of performing
      leg press (LP) 45 degrees  using a physioball and elastic band over multiple sets
      with submaximal loads on electromyographic (EMG) amplitude and fatigue indices.
      METHODS: 18 trained females volunteered (age: 24.4 +/- 2.1 y; height: 168.1 +/- 4
      cm; body mass: 65.1 +/- 4.4 kg) participated in this study. The 10 repetition
      maximum (RM) loads were determined for the LP. Then, 3 experimental protocols
      were followed in a randomized crossover design over 3 nonconsecutive days:
      control protocol-the participants performed 4 LP sets; physioball between knees-4
      LP sets were performed with the physioball between the knees; elastic band-4 LP
      sets were performed with the elastic band involving the knees. Ten repetitions
      were performed during each set with 70% of 10-RM loads; EMG spectral indices
      (CRMS and Cf5) was collected from the biceps femoris (BF), vastus lateralis (VL),
      vastus medialis obliquus (VMO), and rectus femoris (RF) muscles. RESULTS: Higher
      levels of CRMS and Cf5 were noted for RF, VL, and VM muscles using the physioball
      and elastic band when compared with control protocol, respectively. CRMS index of
      BF muscle was significantly higher using physioball and elastic band protocol
      versus control condition, respectively. CONCLUSION: Therefore, both physioball
      and elastic band can be adopted during LP with the goal to reduce excessive varus
      and valgus forces, respectively, even performing consecutive sets with submaximal
      loads. Furthermore, this may be an interesting alternative to increasing
      quadriceps activation and improving the knee joint stabilization.

PMID- 27705076
TI  - Single-Task and Dual-Task Gait Among Collegiate Athletes of Different Sport
      Classifications: Implications for Concussion Management.
AB  - Gait impairments have been documented following sport-related concussion. Whether
      preexisting gait pattern differences exist among athletes who participate in
      different sport classifications, however, remains unclear. Dual-task gait
      examinations probe the simultaneous performance of everyday tasks (ie, walking
      and thinking), and can quantify gait performance using inertial sensors. The
      purpose of this study was to compare the single-task and dual-task gait
      performance of collision/contact and noncontact athletes. A group of collegiate
      athletes (n = 265) were tested before their season at 3 institutions (mean age=
      19.1 +/- 1.1 years). All participants stood still (single-task standing) and
      walked while simultaneously completing a cognitive test (dual-task gait), and
      completed walking trials without the cognitive test (single-task gait). Spatial
      temporal gait parameters were compared between collision/contact and noncontact
      athletes using MANCOVAs; cognitive task performance was compared using ANCOVAs.
      No significant single-task or dual-task gait differences were found between
      collision/contact and noncontact athletes. Noncontact athletes demonstrated
      higher cognitive task accuracy during single-task standing (P = .001) and dual
      task gait conditions (P = .02) than collision/contact athletes. These data
      demonstrate the utility of a dual-task gait assessment outside of a laboratory
      and suggest that preinjury cognitive task performance during dual-tasks may
      differ between athletes of different sport classifications.

PMID- 27705071
TI  - Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review.
AB  - Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus
      (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The
      subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS)
      provokes seizures and, at sufficient doses, centrally-mediated respiratory
      arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral
      signs of intoxication and overstimulation of the muscarinic and nicotinic
      receptors, which is described as "cholinergic crisis" (i.e. diarrhea, sweating,
      salivation, miosis, bronchoconstriction). Exposure to high doses of sarin can
      result in tremors, seizures, and hypothermia. More seriously, build-up of ACh at
      neuromuscular junctions also can cause paralysis and ultimately peripherally
      mediated respiratory arrest which can lead to death via respiratory failure. In
      addition to its primary action on the cholinergic system, sarin possesses other
      indirect effects. These involve the activation of several neurotransmitters
      including gamma-amino-butyric acid (GABA) and the alteration of other signaling
      systems such as ion channels, cell adhesion molecules, and inflammatory
      regulators. Sarin exposure is associated with symptoms of organophosphate-induced
      delayed neurotoxicity (OPIDN) and organophosphate-induced chronic neurotoxicity
      (OPICN). Moreover, sarin has been involved in toxic and immunotoxic effects as
      well as organophosphate-induced endocrine disruption (OPIED). The standard
      treatment for sarin-like nerve agent exposure is post-exposure injection of
      atropine, a muscarinic receptor antagonist, accompanied by an oxime, an AChE
      reactivator, and diazepam.

PMID- 27705077
TI  - Zika Getting on Your Nerves? The Association with the Guillain-Barre Syndrome.

PMID- 27705078
TI  - Changes in Thiol-Disulfide Homeostasis of the Body to Surgical Trauma in
      Laparoscopic Cholecystectomy Patients.
AB  - OBJECTIVE: We aimed to investigate the short-term effect of laparoscopic surgery
      on serum thiol-disulfide homeostasis levels as a marker of oxidant stress of
      surgical trauma in elective laparoscopic cholecystectomy patients. MATERIALS AND
      METHODS: Venous blood samples were collected, and levels of native thiols, total
      thiols, and disulfides were determined with a novel automated assay. Total
      antioxidant capacity (measured as the ferric-reducing ability of plasma) and
      serum ischemia modified albumin, expressed as absorbance units assayed by the
      albumin cobalt binding test, were determined. RESULTS: The major findings of the
      present study were that native thiol (283 +/- 45 versus 241 +/- 61 MUmol/L),
      total thiol (313 +/- 49 versus 263 +/- 67 MUmol/L), and disulfide (14.9 +/- 4.6
      versus 11.0 +/- 6.1 MUmol/L) levels were decreased significantly during operation
      and although they increased, they did not return to preoperation levels 24 hours
      after laparoscopic surgery compared to the levels at baseline. Disulfide/native
      thiol and disulfide/total thiol levels did not change during laparoscopic
      surgery. CONCLUSIONS: The decrease in plasma level of native and total thiol
      groups suggests impairment of the antioxidant capacity of plasma; however, the
      delicate balance between the different redox forms of thiols was maintained
      during surgery.

PMID- 27705079
TI  - Gender Differences in Outpatient Utilization: A Pooled Analysis of Data from the
      Korea Health Panel.
AB  - BACKGROUND: This study aims to set itself apart from prior research by
      elucidating gender differences in outpatient service utilization among adults
      aged 20 years or older, using nationally representative survey data. METHODS:
      Data from the Korea Health Panel (KHP) collected between 2010 and 2011 were used.
      In this study, all KHP participants who accessed outpatient service between 2010
      and 2011 were included; 13,525 participants used outpatient services in 2010 and
      12,991 in 2011. To analyze factors related to outpatient utilization, regression
      analysis was performed using generalized estimating equations. RESULTS: The use
      frequency of outpatient service was significantly associated with age, education
      level, marital status, economic activity, health insurance status, drinking,
      presence of chronic disease, and self-rated health status in both sexes (p <
      0.05). Annual household income significantly affected outpatient utilization only
      among women. CONCLUSIONS: Unlike males, females with higher household incomes
      used outpatient services more. This suggests that females are at greater risk of
      medical inequality based on economic circumstances.

PMID- 27705080
TI  - Generation of Pax1/PAX1-Specific Monoclonal Antibodies.
AB  - Pax genes encode an evolutionary conserved group of transcription factors with
      multiple roles during embryonic development and for cell type specification in
      normal and malignant tissues of the adult organism. In mice, Pax1 is required for
      the formation of specific skeletal structures as well as for the development of a
      fully functional thymus. In humans, the PAX1 locus has been linked to
      otofaciocervical syndrome, idiopathic scoliosis, and to a higher susceptibility
      for androgenic alopecia. In addition, the methylation status of PAX1 has recently
      emerged as a sensitive marker for predictive screening of cervical cancer. To
      provide a reagent for reproducible detection of Pax1 expression, we have
      generated rat monoclonal antibodies (MAbs) against the murine Pax1 protein. MAbs
      of one clone (clone 5A2) specifically detect mouse Pax1 protein in Western blot
      analyses. Moreover, the anti-Pax1 MAbs cross-react with human PAX1 protein and
      are applicable in immunohistochemical detection procedures using
      paraformaldehyde/formalin-fixed tissues embedded in paraffin. The anti-Pax1 MAbs
      provide a reliable reagent for reproducible Pax1/PAX1 protein expression analyses
      and, therefore, may help to improve diagnostic protocols in clinical settings
      involving deregulated expression of Pax1/PAX1.

PMID- 27705081
TI  - Approach to Recurrent Congenital Diaphragmatic Hernia: Results of an
      International Survey.
AB  - PURPOSE: Although recurrence remains one of the most feared complications
      following congenital diaphragmatic hernia (CDH) repair, there are minimal data on
      the optimal surgical approach to these complex situations. The purpose of this
      study was to survey the international pediatric surgery community to ascertain
      practice patterns for both minimally invasive (MIS) and open approaches for
      recurrent CDH. MATERIALS AND METHODS: A survey was e-mailed to members of an
      online community of pediatric surgeons. The questionnaire elicited surgeons'
      clinical experience, the continent in which they practice, and their surgical
      approach (laparotomy, thoracotomy, laparoscopy, or thoracoscopy) to five clinical
      cases, including initial and recurrent Bochdalek hernias. Fisher's exact test and
      chi-square test were used for statistical analysis. RESULTS: Two-hundred eighty
      pediatric surgeons responded to the survey. In total, 52.1% of surgeons chose an
      MIS approach for an initial repair of left CDH with the younger surgeons more
      likely to use an MIS approach. For the recurrence scenarios, 42.5%-55.5% of these
      surgeons would attempt an MIS repair after a recurrence. Specifically,
      thoracoscopy was favored over laparoscopy following both prior laparotomy (30.0%
      versus 7.5%) and prior right thoracoscopy (26.4% versus 10.0%), less favored
      following thoracotomy (9.3% versus 18.9%), and relatively similar proportions
      following prior left thoracoscopy (17.5% versus 16.4%). Laparotomy was the
      preferred open approach both for initial presentation and all recurrence
      scenarios. Among surgeons who would treat initial CDH with an open procedure,
      between 10.4% and 17.9% would switch to an MIS approach, most commonly after
      prior failed laparotomy. CONCLUSIONS: Approximately half surgeons who approach
      initial left CDH in an MIS manner would attempt an MIS approach for recurrence.
      The tendency to approach CDH recurrence from the opposite body cavity as the
      initial repair clearly impacted the surgical approach. This was particularly
      pronounced for MIS repairs, whereas for open approach, laparotomy remained, by
      far, the most popular in all scenarios.

PMID- 27705082
TI  - Is Single-Port Laparoscopy More Precise and Faster with the Robot?
AB  - BACKGROUND: Single-port laparoscopy is a step forward toward nearly scar less
      surgery. Concern has been raised that single-incision laparoscopic surgery (SILS)
      is technically more challenging because of the lack of triangulation and the
      clashing of instruments. Robotic single-incision laparoscopic surgery (RSILS) in
      chopstick setting might overcome these problems. This study evaluated the outcome
      in time and errors of two tasks of the Fundamentals of Laparoscopic Surgery on a
      dry platform, in two settings: SILS versus RSILS. METHODS: Nine experienced
      laparoscopic surgeons performed two tasks: peg transfer and a suturing task, on a
      standard box trainer. All participants practiced each task three times in both
      settings: SILS and a RSILS setting. The assessment scores (time and errors) were
      recorded. RESULTS: For the first task of peg transfer, RSILS was significantly
      better in time (124 versus 230 seconds, P = .0004) and errors (0.80 errors versus
      2.60 errors, P = .024) at the first run, compared to the SILS setting. At the
      third and final run, RSILS still proved to be significantly better in errors
      (0.10 errors versus 0.80 errors, P = .025) compared to the SILS group. RSILS was
      faster in the third run, but not significant (116 versus 157 seconds, P = .08).
      For the second task, a suturing task, only 3 participants of the SILS group were
      able to perform this task within the set time frame of 600 seconds. There was no
      significant difference in time in the three runs between SILS and RSILS for the 3
      participants that fulfilled both tasks within the 600 seconds. CONCLUSIONS: This
      study shows that robotic single-port surgery seems easier, faster, and more
      precise to perform basis tasks of the Fundamentals of laparoscopic surgery. For
      the more complex task of suturing, only the single-port robotic setting enabled
      all participants to fulfill this task, within the set time frame.

PMID- 27705083
TI  - Comparing High Definition Live Interactive and Store-and-Forward Consultations to
      In-Person Examinations.
AB  - BACKGROUND: There is little teledermatology research directly comparing remote
      methods, even less research with two in-person dermatologist agreement providing
      a baseline for comparing remote methods, and no research using high definition
      video as a live interactive method. OBJECTIVE: To compare in-person consultations
      with store-and-forward and live interactive methods, the latter having two levels
      of image quality. METHODS: A controlled study was conducted where patients were
      examined in-person, by high definition video, and by store-and-forward methods.
      The order patients experienced methods and residents assigned methods rotated,
      although an attending always saw patients in-person. The type of high definition
      video employed, lower resolution compressed or higher resolution uncompressed,
      was alternated between clinics. Primary and differential diagnoses, biopsy
      recommendations, and diagnostic and biopsy confidence ratings were recorded.
      RESULTS: Concordance and confidence were significantly better for in-person
      versus remote methods and biopsy recommendations were lower. Store-and-forward
      and higher resolution uncompressed video results were similar and better than
      those for lower resolution compressed video. LIMITATIONS: Dermatology residents
      took store-and-forward photos and their quality was likely superior to those
      normally taken in practice. There were variations in expertise between the
      attending and second and third year residents. CONCLUSION: The superiority of in
      person consultations suggests the tendencies to order more biopsies or still see
      patients in-person are often justified in teledermatology and that high
      resolution uncompressed video can close the resolution gap between store-and
      forward and live interactive methods.

PMID- 27705084
TI  - Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis.
AB  - BACKGROUND: Levosimendan is a calcium-sensitizing drug with inotropic and other
      properties that may improve outcomes in patients with sepsis. METHODS: We
      conducted a double-blind, randomized clinical trial to investigate whether
      levosimendan reduces the severity of organ dysfunction in adults with sepsis.
      Patients were randomly assigned to receive a blinded infusion of levosimendan (at
      a dose of 0.05 to 0.2 MUg per kilogram of body weight per minute) for 24 hours or
      placebo in addition to standard care. The primary outcome was the mean daily
      Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to
      day 28 (scores for each of five systems range from 0 to 4, with higher scores
      indicating more severe dysfunction; maximum score, 20). Secondary outcomes
      included 28-day mortality, time to weaning from mechanical ventilation, and
      adverse events. RESULTS: The trial recruited 516 patients; 259 were assigned to
      receive levosimendan and 257 to receive placebo. There was no significant
      difference in the mean (+/-SD) SOFA score between the levosimendan group and the
      placebo group (6.68+/-3.96 vs. 6.06+/-3.89; mean difference, 0.61; 95% confidence
      interval [CI], -0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the
      levosimendan group and 30.9% in the placebo group (absolute difference, 3.6
      percentage points; 95% CI, -4.5 to 11.7; P=0.43). Among patients requiring
      ventilation at baseline, those in the levosimendan group were less likely than
      those in the placebo group to be successfully weaned from mechanical ventilation
      over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03).
      More patients in the levosimendan group than in the placebo group had
      supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7
      percentage points; 95% CI, 0.1 to 5.3; P=0.04). CONCLUSIONS: The addition of
      levosimendan to standard treatment in adults with sepsis was not associated with
      less severe organ dysfunction or lower mortality. Levosimendan was associated
      with a lower likelihood of successful weaning from mechanical ventilation and a
      higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and
      Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials
      number, ISRCTN12776039 .).

PMID- 27705085
TI  - The Onset of Intra-Abdominal Adhesions During Closed-Abdomen Hyperthermic
      Intraperitoneal Chemotherapy.
AB  - INTRODUCTION: Hyperthermic intraperitoneal chemotherapy (HIPEC) is delivered
      after cytoreductive surgery (CRS) in selected patients with peritoneal
      carcinomatosis. The closed-abdomen technique, preferred by many centers, prevents
      heat loss and drug spillage, but does not warrant homogeneous distribution of the
      perfusion fluid (PF). The hypothesized formation of intra-abdominal adhesions
      during the closed-abdomen perfusion period has never been described. MATERIALS
      AND METHODS: From March 2014 to April 2016, 10 consecutive patients with
      peritoneal carcinomatosis, selected for CRS, underwent the Laparoscopy-Enhanced
      HIPEC technique to explore the abdominal cavity during the perfusion. The aim of
      the study was to investigate the incidence and the extent of intra-abdominal
      adhesions that are formed after CRS during the perfusion period of closed-abdomen
      HIPEC. RESULTS: During the perfusion, adhesions developed in 70% of the patients.
      Adhesions developed mainly in the period between the closure of the abdomen and
      the subsequent filling of the abdomen with the PF. After their first division,
      during the following perfusion period, adhesions between the bowel and the
      abdominal wall reformed in 3 patients (30%). CONCLUSIONS: Intra-abdominal
      adhesions are frequently formed during closed-abdomen HIPEC and can hamper the
      adequate circulation of the PF. The Laparoscopy-Enhanced technique enables the
      early detection and the division of any intra-abdominal adhesions.

PMID- 27705086
TI  - Transdiagnostic group CBT for anxiety disorders: the unified protocol in mental
      health services.
AB  - Comorbidity among the anxiety disorders is common and may negatively impact
      treatment outcome. Potentially, transdiagnostic cognitive-behavioral treatments
      (CBT) deal more effectively with comorbidity than standard CBT. The present study
      tested the effectiveness of The Unified Protocol (UP) applied to Mental Health
      Services. Pre-post-treatment effects were examined for psychiatric outpatients
      with anxiety disorders receiving UP treatment in groups. Forty-seven patients
      (mean-age = 34.1 (SD = 9.92), 77% females) with a principal diagnosis of anxiety
      were included. We found significant and clinically meaningful changes in the
      primary outcomes Clinical Global Impression Severity Scale (CGI-S; d = 1.36),
      Hamilton Anxiety Scale (HARS; d = .71), and WHO-5 Well-being Index (WHO-5; d =
      .54). Also, comorbid depressive symptoms and levels of positive and negative
      affect changed significantly after treatment. Patients with high levels of
      comorbidity profited as much as patients with less comorbidity; however, these
      patients had higher scores after treatment due to higher symptom burden at onset.
      Patients with comorbid depression profited more from treatment than patients
      without comorbid depression. The treatment effects found in the present study
      correspond to treatment effects of other TCBT studies, other UP group studies,
      and effectiveness studies on standard CBT for outpatients. The results indicate
      that the UP can be successfully applied to a MHS group setting, demonstrating
      positive effects on anxiety and depressive symptoms for even highly comorbid
      cases.

PMID- 27705087
TI  - Measurement of neurodevelopmental changes in children treated with radiation for
      brain tumors: what is a true 'baseline?'
AB  - OBJECTIVE: To review the various ways in which baseline neuropsychological
      functioning is measured in the extant literature on pediatric brain tumors,
      describe the pros and cons of each approach, and increase the awareness of
      researchers as to the implications of each. METHOD: We reviewed the literature
      from 1993 to 2013, and classified studies by baseline approach and explicitness
      of selection of approach. RESULTS: There are multiple approaches to
      operationalizing baseline levels of ability and to assess change from baseline.
      Each approach has strengths and weaknesses, and selection may depend on the
      question under investigation. Approaches to baseline estimation varied widely
      with a trend over time toward reliance on statistical modeling. Researchers were
      often insufficiently explicit about the reasons for adopting a particular
      approach. The common use of standardized scores requires caution as they obscure
      critical inferential limitations about change and magnitude of change. Some
      viable approaches were infrequently used, such as actuarial prediction formulas.
      Multiple simultaneous methods akin to theory testing and formal methods of
      construct validation could enhance scientific yield since all approaches are
      fallible. CONCLUSIONS: Estimating baseline neuropsychological functioning is very
      challenging, particularly when it concerns children in the preschool years.
      Nevertheless, it is a crucial methodological decision with important implications
      for the interpretation of research findings that needs to be dealt with
      explicitly.

PMID- 27705088
TI  - Thoracoscopic Lobectomy in Infants and Children Utilizing a 5 mm Stapling Device.
AB  - PURPOSE: Thoracoscopic lobectomy for congenital cystic lung disease has become an
      accepted and in many institutions the preferred technique. However, the technical
      challenges are many. Previous endoscopic staplers (12 mm) used commonly in adults
      are too large for use in infants This study evaluates the safety and efficacy of
      using a 5 mm stapling device to seal and divide major pulmonary structures.
      METHODS: From July 2014 to March 2016, 26 patients of age 6 weeks to 13 months
      underwent thoracoscopic lobectomy for CPAM or sequestration. Weights ranged from
      3.2 to 11.4 kg. There were 7 upper lobectomies, 2 middle, and 17 lower
      lobectomies. In each case, the 5 mm stapler (Justright Surgical; Louisville,
      Colorado) was the primary device for vessel and bronchial sealing and division.
      It is 4.8 mm in diameter with an anvil length of 25 mm and lays down four rows of
      staples and divides between them. A 3 mm sealing device was used for dissection
      and to take smaller segmental vessels as necessary. Stump lines were evaluated
      for bleeding or air leak in all cases. RESULTS: All procedures were accomplished
      successfully thoracoscopically. The stapler was used on the main lobar artery
      cases and vein in 24 cases, a large systemic sequestration vessel in 5 cases, and
      the bronchus in all 26. The stapler was also used to complete the minor fissure
      in 1 case and the major fissure in 1 case. A total of 96 staple loads were fired.
      Operative times ranged from 35 to 135 minutes. There was no significant bleeding
      of any vascular stump. In 1 case, the edge of the bronchial stump had to be
      reinforced, this was thought to be secondary to too much tissue being enclosed in
      the jaws. There were no postoperative complications. CONCLUSION: The use of a 5
      mm stapling device appears to be safe and effective in thoracoscopic lobectomy in
      infants. It allows for safe management of major pulmonary vessels and bronchi in
      the confined chest of an infant through a single 5 mm port.

PMID- 27705089
TI  - Drug Initiation of Female Detainees in a Compulsory Drug Treatment Institution in
      China.
AB  - This study explored drug initiation among 46 Chinese women in a compulsory drug
      treatment institution. The study adopted a mixed method with a strong emphasis on
      qualitative techniques to capture the perspectives of women in long-term
      treatment regarding their drug initiation experiences. A complementary analysis
      of quantitative data was used to help interpret, refine, deepen, and extend
      qualitative findings. Participants were divided into two groups according to
      their main drug of choice: 27 used methamphetamines and 19 used heroin (11 of
      them used methamphetamines occasionally). Four main themes were identified in the
      analysis of participants' drug initiation narratives: (1) involvement in high
      risk social networks; (2) lack of family love and support; (3) relationship
      problems; and (4) male partner influence. Findings indicate that the younger
      generation preferred starting their drug career with methamphetamines rather than
      heroin, due to the changes in the drug market and broader changes related to
      globalization. A lack of family love and support had a strong effect on the
      initiation of methamphetamine but not heroin users; however, male intimate
      partners and relationship issues showed strong influence on heroin initiation.
      Having high-risk social networks was a common narrative in the drug use
      initiation of Chinese women across methamphetamine and heroin groups.

PMID- 27705090
TI  - Spontaneous confabulations in amnestic-mild cognitive impairment due to
      Alzheimer's disease: a new (yet old) atypical variant?
AB  - Confabulation may be present in Alzheimer's disease (AD), but usually it is not a
      primary feature of either its typical or atypical variants. In this report, we
      describe the case of an AD patient who showed an unusual and enduring
      neuropsychiatric phenotype characterized by early and prominent spontaneous
      confabulation. Surprisingly, such atypical AD presentation bears a striking
      resemblance to presbyophrenia, a subtype of dementia which was described at the
      beginning of the twentieth century and then sank into oblivion. In discussion, we
      speculate on the "return" of presbyophrenia as an unrecognized neuropsychiatric
      variant of AD and its possible neuroanatomical substrates.

PMID- 27705091
TI  - Guillain-Barre Syndrome Associated with Zika Virus Infection in Colombia.
AB  - BACKGROUND: Zika virus (ZIKV) infection has been linked to the Guillain-Barre
      syndrome. From November 2015 through March 2016, clusters of cases of the
      Guillain-Barre syndrome were observed during the outbreak of ZIKV infection in
      Colombia. We characterized the clinical features of cases of Guillain-Barre
      syndrome in the context of this ZIKV infection outbreak and investigated their
      relationship with ZIKV infection. METHODS: A total of 68 patients with the
      Guillain-Barre syndrome at six Colombian hospitals were evaluated clinically, and
      virologic studies were completed for 42 of the patients. We performed reverse
      transcriptase-polymerase-chain-reaction (RT-PCR) assays for ZIKV in blood,
      cerebrospinal fluid, and urine, as well as antiflavivirus antibody assays.
      RESULTS: A total of 66 patients (97%) had symptoms compatible with ZIKV infection
      before the onset of the Guillain-Barre syndrome. The median period between the
      onset of symptoms of ZIKV infection and symptoms of the Guillain-Barre syndrome
      was 7 days (interquartile range, 3 to 10). Among the 68 patients with the
      Guillain-Barre syndrome, 50% were found to have bilateral facial paralysis on
      examination. Among 46 patients in whom nerve-conduction studies and
      electromyography were performed, the results in 36 patients (78%) were consistent
      with the acute inflammatory demyelinating polyneuropathy subtype of the Guillain
      Barre syndrome. Among the 42 patients who had samples tested for ZIKV by RT-PCR,
      the results were positive in 17 patients (40%). Most of the positive RT-PCR
      results were in urine samples (in 16 of the 17 patients with positive RT-PCR
      results), although 3 samples of cerebrospinal fluid were also positive. In 18 of
      42 patients (43%) with the Guillain-Barre syndrome who underwent laboratory
      testing, the presence of ZIKV infection was supported by clinical and immunologic
      findings. In 20 of these 42 patients (48%), the Guillain-Barre syndrome had a
      parainfectious onset. All patients tested were negative for dengue virus
      infection as assessed by RT-PCR. CONCLUSIONS: The evidence of ZIKV infection
      documented by RT-PCR among patients with the Guillain-Barre syndrome during the
      outbreak of ZIKV infection in Colombia lends support to the role of the infection
      in the development of the Guillain-Barre syndrome. (Funded by the Bart McLean
      Fund for Neuroimmunology Research and others.).

PMID- 27705093
TI  - Physical Activity and Adiposity Among Older Adults of the EVIDENT Study.
AB  - This study determined the relationship between self-reported and objective
      measurements of physical activity with adiposity markers in a random sample of
      community-dwelling older adults. The sample included 439 individuals over 65
      years (age 71.1 +/- 7.8; 54.2% women). Regular physical activity information was
      collected using self-reported (questionnaire, 7-day-PAR) and objective
      measurements (accelerometer ActiGraph GT3X) over 7 days. Anthropometric
      parameters included body mass index, body fat percentage, and waist
      circumference. The number of patients considered active was 28% according to the
      results of 7-day PAR, and 69% according to objective measures of accelerometry.
      With every daily increase of 10 min of sedentary activity, the BMI, body fat
      percentage, and waist circumference values increased by 0.04 units, 0.14%, and
      0.14 cm, respectively. According to the accelerometry data, being active was a
      protective factor for presenting obesity criteria (OR = 0.34, CI 95% 0.19-0.59).
      Objective but non self-reported physical activity was associated with adiposity
      markers in older adults.

PMID- 27705092
TI  - An fMRI study on the comparison of different types of false belief reasoning:
      False belief-based emotion and behavior attribution.
AB  - False belief (FB) reasoning is a key Theory of Mind (ToM) competence. By 4 years
      of age, children understand that a person's behavior can be based on a FB about
      reality. Children cannot understand that a person's emotion can also be based on
      a FB before the age of six. In order to generate hypothesis on basic processes
      distinguishing these two types of belief reasoning, the present functional
      magnetic resonance imaging study in adults directly compares functional activity
      associated with these two FB tasks. Both tasks were associated with activity in
      the ToM network including the medial prefrontal cortex and the left temporo
      parietal junction. Differential activity was observed in the anterior
      dorsolateral prefrontal cortex for FB-based emotion relative to behavior
      attribution. Contrary to FB behavior attribution, FB-based emotion attribution
      requires the processing of two different mental states: a belief and an emotion
      and their relation to each other. The activity pattern may reflect the
      differential demands on cognitive processes associated with the two different
      belief-based attribution processes. These results shed new light on the still
      ongoing debate about the nature of the developmental lag between the two FB
      tasks.

PMID- 27705094
TI  - Population Health Measurement at Centers for Medicare & Medicaid Services:
      Bridging the Gap Between Public Health and Clinical Quality.
AB  - As Medicare and Medicaid increasingly shift to alternative payment models focused
      on population-based payments, there is an urgent need to develop measures of
      population health that can drive health improvement. In response, an assessment
      and design project established a framework for developing population health
      measures from a payer perspective, conducted environmental scans of existing
      measures and available data infrastructure, and conducted a gap analysis
      informing measure development and infrastructure needs. The work, summarized
      here, makes recommendations for creating a set of core measures, demonstrates
      some of the key challenges in applying a traditional quality measure development
      framework to population health, and complements recent efforts by the National
      Academy of Medicine and others with a focus on a payer perspective.

PMID- 27705095
TI  - Telerehabilitation in Stroke Recovery: A Survey on Access and Willingness to Use
      Low-Cost Consumer Technologies.
AB  - : Background/Introduction: Early telerehabilitation trials with stroke survivors
      have shown promising results, but there remains a lack of knowledge of what areas
      of rehabilitation people with stroke are interested and willing to receive using
      technology. The purpose of this study was to describe the access to low-cost
      consumer technologies and willingness to use them to receive rehabilitation
      services among stroke survivors. MATERIALS AND METHODS: Participants were
      included in this survey study if they had a stroke, lived in the community, were
      19 years of age or older, and able to understand English. Participants completed
      a study-specific telerehabilitation survey via phone call, mail, in-person, or
      online. Descriptive statistics were used to characterize the sample and survey
      responses. RESULTS: One hundred two survey responses were returned, representing
      a 79.1% response rate. The mean age of this urban (67.3%) and rural (32.7%)
      sample was 67.6 years. The technologies most commonly owned were as follows:
      televisions (91%), landline telephones (88.0%), and computers (79.0%). A large
      proportion of the sample reported an interest to receive assessments (58.4%),
      training and exercise programs (64.0%), and education (61.4%) via
      telerehabilitation, however, many were not interested to receive
      telerehabilitation (~39%) and believed that the quality of care would be less
      than in-person rehabilitation (71.0%). CONCLUSIONS: The use of consumer
      technologies for the delivery of rehabilitation services is both feasible and
      desirable by stroke survivors. Telerehabilitation services at present should
      augment and not replace in-person rehabilitation. However, in cases where in
      person rehabilitation is neither accessible nor possible, telerehabilitation
      could serve as an acceptable alternative and is a key area for future research.

PMID- 27705096
TI  - The Occurrence of Trichinella spp. in Red Foxes (Vulpes vulpes) in Different
      Regions of Poland: Current Data.
AB  - Trichinellosis is one of the most widespread parasitic zoonoses. Trichinella
      Owen, 1835 nematodes are found in pigs, horses, and humans in the domestic cycle,
      and in many carnivores and omnivores in the sylvatic cycle, such as wild boars,
      red foxes, raccoon dogs, and wolves. Carnivores are known to be involved in the
      circulation of Trichinella nematodes and they act as a reservoir in the sylvatic
      environment. The aim of this study was to determine the occurrence of Trichinella
      spp. infection in red foxes in Poland. Samples were collected from 2010 to 2015
      in different regions of the country and then tested for Trichinella nematodes
      using HCl-pepsin digestion. Trichinella larvae were found in 10.02% of examined
      samples (145/1447). The larvae were identified as T. spiralis (11.03%), T.
      britovi (71.72%), and T. pseudospiralis (0.69%). No mixed infection was observed.
      The prevalence of infection varied between years and different voivodeships of
      the country. Our findings confirm that red foxes are involved in the maintenance
      of Trichinella spp. in the sylvatic cycle in Poland.

PMID- 27705097
TI  - A Comparative Study on the Transareola Single-Site Versus Three-Port Endoscopic
      Thyroidectomy.
AB  - OBJECTIVE: To explore the feasibility, safety, and advantages of transareola
      single-site endoscopic thyroidectomy. METHODS: From January 2014 to December
      2015, 40 patients were randomly divided into an observation group who received
      single-site endoscopic thyroidectomy by the areola approach and a control group
      who underwent three-port endoscopic thyroidectomy by the areola approach with 20
      patients in each group. The feasibility and safety of the operation and
      postoperative clinical outcomes were compared between these two groups. RESULTS:
      There was no significant difference in operation time, intraoperative blood loss,
      and hospitalization time (P > .05) between the two groups. The subcutaneous
      dissection area in the observation group (130 [120-130] cm2) was significantly
      smaller than that in the control group (180 [170-190] cm2) (P < .01). In
      addition, there is much less postoperative drainage in the observation group (70
      [50-80] mL) than in the control group (80 [60-100] mL) (P = .036). Furthermore,
      24-hour postoperative pain score in the observation group (4.0 [3.0-5.5]) was
      significantly lower compared with that in the control group (5.0 [4.0-7.0]) (P =
      .047). Moreover, patients in the observation group present with significantly
      higher 7-day postoperative cosmetic satisfaction scores (9.0 [8.0-9.0]) than
      those in the control group (7.0 [7.0-8.0]) (P < .001). CONCLUSION: Transareola
      single-site endoscopic thyroidectomy exhibits superior advantages in clinical
      outcomes such as causing less pain and achieving better cosmetic satisfaction,
      compared with three-port endoscopic thyroidectomy.

PMID- 27705099
TI  - Traffic safety research - the unfinished research agenda.

PMID- 27705100
TI  - Chi-squared statistics of association and homogeneity.

PMID- 27705102
TI  - Toxoplasmatinae Parasites in Bats from Bahia State, Brazil.
AB  - Toxoplasma gondii and Neospora caninum are widespread cyst-forming coccidian
      parasites of the subfamily Toxoplasmatinae that infect a wide range of wild and
      domestic animals. Whereas T. gondii is a zoonotic disease, N. caninum is
      restricted to nonhuman animals. Some chiropteran species can be infected by T.
      gondii and present fatal toxoplasmosis. In most cases, T. gondii -infected bats
      are believed to remain asymptomatic and to act as an infection source to other
      animals. It is not known whether N. caninum can infect bats. We determined
      infection rates of T. gondii and N. caninum in free-living bats in the state of
      Bahia, Brazil. Brain samples from 97 bats of seven species, captured in 2008-15,
      were analyzed by PCRs for T. gondii and N. caninum . Two of the 97 samples were
      positive for T. gondii DNA. None of the samples were positive for N. caninum DNA,
      suggesting that the bats were not susceptible to N. caninum infection or that its
      prevalence was very low.

PMID- 27705101
TI  - Chemical Restraint of Free-ranging South American Coatis ( Nasua nasua ) with a
      Combination of Tiletamine and Zolazepam.
AB  - We describe the use of a combination of tiletamine and zolazepam (Zoletil(r)) for
      chemical restraint of South American coatis ( Nasua nasua ) under field
      conditions. We immobilized 53 coatis from a free-ranging population at Iguacu
      National Park, Brazil, with Zoletil. Males and females (1.0-8.7 kg) of different
      age groups participated in the study. Four dosage (milligram per kilogram body
      weight) groups were created based on quartiles as follows: 1) 4.76-6.68 mg/kg
      (n=13), 2) 6.83-7.71 mg/kg (n=13), 3) 7.72-8.68 mg/kg (n=18), and 4) 8.98-11.57
      mg/kg (n=9). Variables analyzed were sex, age, body weight, dosage, induction
      time, handling time (HT: time elapsed between the onset of immobilization and
      first signs of recovery), time from injection to first stand-up posture after
      anesthesia, heart and respiratory rates, and body temperature. Mean (+/-SD)
      induction time was 2.9 (+/-1.4) min and was positively correlated with age. In
      dosage groups 1-4, mean HTs were 40.3 (+/-24.0), 64.5 (+/-19.1), 54.8 (+/-15.0),
      and 60.3 (+/-12.0), respectively. Handling time had a positive linear
      relationship with age and body weight, but the relationship between HT and dosage
      was nonlinear. Group 1 had a shorter HT compared to the other groups combined.
      Time from injection to first stand-up was 105.0 (+/-33.5) min. Zoletil was quick
      acting and safe for immobilization of coatis in the wild.

PMID- 27705103
TI  - RETROSPECTIVE ANALYSIS OF THE EPIDEMIOLOGIC LITERATURE, 1990-2015, ON WILDLIFE
      ASSOCIATED DISEASES FROM THE REPUBLIC OF KOREA.
AB  - To assess the status of research on wildlife diseases in the Republic of Korea
      (ROK) and to identify trends, knowledge gaps, and directions for future research,
      we reviewed epidemiologic publications on wildlife-associated diseases in the
      ROK. We identified a relatively small but rapidly increasing body of literature.
      The majority of publications were focused on public or livestock health and
      relatively few addressed wildlife health. Most studies that focused on human and
      livestock health were cross-sectional whereas wildlife health studies were mostly
      case reports. Fifteen diseases notifiable to the World Organisation for Animal
      Health were identified and 21 diseases were identified as notifiable to either
      the Korea Ministry of Health and Welfare or the Korea Ministry of Agriculture,
      Food and Rural Affairs. Two diseases were reported as occurring as epidemics;
      highly pathogenic avian influenza (HPAI) and virulent Newcastle disease. Six
      diseases or disease agents were described in the literature as emerging including
      HPAI, rabies, Babesia microti , avian coronaviruses, scrub typhus, and severe
      fever thrombocytopenia syndrome virus. The diseases for which there were the
      largest number of publications were HPAI and rabies. The majority of wildlife
      associated zoonotic disease publications focused on food-borne parasitic
      infections or rodent-associated diseases. Several publications focused on the
      potential of wildlife as reservoirs of livestock diseases; in particular, Korean
      water deer ( Hydropotes inermis argyropus ) and wild boar ( Sus scrofa ). In
      contrast, there were few publications on diseases of concern for wildlife
      populations or research to understand the impacts of these diseases for wildlife
      management. Increased focus on prospective studies would enhance understanding of
      disease dynamics in wildlife populations. For the high-consequence diseases that
      impact multiple sectors, a One Health approach, with coordination among the
      public health, agricultural, and environmental sectors, would be important. This
      type of review can provide useful information for countries or regions planning
      or implementing national wildlife health programs.

PMID- 27705104
TI  - A Serosurvey of Greater Sage-Grouse ( Centrocercus urophasianus ) in Nevada, USA.
AB  - To better understand the potential avian diseases in Greater Sage-grouse (
      Centrocercus urophasianus ) in the Great Basin in Nevada, US, we collected 31
      blood samples March-April 2014 and tested for antibodies to eight viruses and two
      bacteria. Specifically, sera were tested for antibodies to avian leukosis virus
      type A, B, and J (ALV-A, ALV-B, and ALV-J, respectively), infectious bursal
      disease virus, infectious bronchitis virus, reticuloendothelial virus, avian
      influenza virus (AIV), West Nile virus, Pasteurella multocida (PM), and
      Salmonella enterica serovar Pullorum. Serum antibodies against ALV-A and -B
      (1/31, 3%), ALV-J (5/31, 16%), PM (1/31, 3%), and AIV (2/31, 6%) were detected by
      enzyme-linked immunosorbent assay (ELISA). While ELISA tests used have only been
      validated in domestic poultry, the serologic data should be used as a potential
      indicator of the range of bacterial and viral infectious agents that can infect
      the Greater Sage-grouse.

PMID- 27705181
TI  - Birth at 22 gestational weeks: case report of cognitive resilience.
AB  - OBJECTIVE: Children delivered at the edge of viability are at greatest risk of
      medical and neuropsychological disability, their adverse outcomes overshadowing
      extremely preterm survivors with more optimal outcomes. We aimed to describe an
      exceptionally early-born extremely preterm (EEEP) preschooler whose
      neurobiological, familial, and socioeconomic factors likely influenced her
      unexpected cognitive resilience. METHOD: Baby G was a 3-years 10-months-old,
      English-speaking, Caucasian, singleton girl born weighing 435 g at 225/7 weeks'
      gestation to well-educated married parents. Neonatal complications of extremely
      premature birth included sepsis, severe respiratory distress syndrome, patent
      ductus arteriosus requiring ligation, necrotizing enterocolitis not requiring
      surgical intervention, and retinopathy of prematurity. Intellectual and
      neuropsychological testing was administered. RESULTS: Baby G performed age
      appropriately in nearly all domains and did not exhibit intellectual deficits.
      Her general conceptual ability was above average for both her chronological and
      adjusted ages. She had below average performance on tests of motor function,
      working memory, and delayed recall of spatial locations. Standardized parental
      behavioral questionnaires indicated no concern in emotional or attentional
      functioning except in relation to mental shifting capacity and signs of anxiety.
      CONCLUSION: Report of persistent adverse neurodevelopmental/neuropsychological
      disabilities following EEEP birth is a counterpoint to the more optimal outcomes
      in some vulnerable EEEP survivors. This case emphasizes that decisions about
      aggressive resuscitation and prognostication for infants born EEEP may be
      enhanced by consideration of individual variability, and of pertinent medical,
      socioeconomic, and sociodemographic variables that may be more predictive of
      neuropsychological outcomes than birth weight and gestational age.

PMID- 27705182
TI  - ?

PMID- 27705183
TI  - ?

PMID- 27705180
TI  - Preschool predictors of school-age academic achievement in autism spectrum
      disorder.
AB  - OBJECTIVE: Characterization of academic functioning in children with autism
      spectrum disorder (ASD), particularly predictors of achievement, may have
      important implications for intervention. The current study aimed to characterize
      achievement profiles, confirm associations between academic ability and
      concurrent intellectual and social skills, and explore preschool predictors of
      school-age academic achievement in a sample of children with ASD. METHOD:
      Children with ASD (n = 26) were evaluated at the approximate ages of two, four,
      and ten. Multiple regression was used to predict school-age academic achievement
      in reading and mathematics from both concurrent (i.e. school-age) and preschool
      variables. RESULTS: Children with ASD demonstrated a weakness in reading
      comprehension relative to word reading. There was a smaller difference between
      mathematics skills; math reasoning was lower than numerical operations, but this
      did not quite reach trend level significance. Concurrent IQ and social skills
      were associated with school-age academic achievement across domains. Preschool
      verbal abilities significantly predicted school-age reading comprehension, above
      and beyond concurrent IQ, and early motor functioning predicted later math
      skills. CONCLUSIONS: Specific developmental features of early ASD predict
      specific aspects of school-age achievement. Early intervention targeting language
      and motor skills may improve later achievement in this population.

PMID- 27705184
TI  - ?

PMID- 27705186
TI  - ?

PMID- 27705185
TI  - ?

PMID- 27705187
TI  - ?

PMID- 27705188
TI  - ?

PMID- 27705189
TI  - ?

PMID- 27705190
TI  - ?

PMID- 27705191
TI  - ?

PMID- 27705193
TI  - ?

PMID- 27705192
TI  - ?

PMID- 27705194
TI  - ?

PMID- 27705195
TI  - ?

PMID- 27705247
TI  - State Regulations and Opioid Use among Disabled Adults.

PMID- 27705248
TI  - State Regulations and Opioid Use among Disabled Adults.

PMID- 27705249
TI  - Life Expectancy after Myocardial Infarction, According to Hospital Performance.
AB  - BACKGROUND: Thirty-day risk-standardized mortality rates after acute myocardial
      infarction are commonly used to evaluate and compare hospital performance.
      However, it is not known whether differences among hospitals in the early
      survival of patients with acute myocardial infarction are associated with
      differences in long-term survival. METHODS: We analyzed data from the Cooperative
      Cardiovascular Project, a study of Medicare beneficiaries who were hospitalized
      for acute myocardial infarction between 1994 and 1996 and who had 17 years of
      follow-up. We grouped hospitals into five strata that were based on case-mix
      severity. Within each case-mix stratum, we compared life expectancy among
      patients admitted to high-performing hospitals with life expectancy among
      patients admitted to low-performing hospitals. Hospital performance was defined
      by quintiles of 30-day risk-standardized mortality rates. Cox proportional
      hazards models were used to calculate life expectancy. RESULTS: The study sample
      included 119,735 patients with acute myocardial infarction who were admitted to
      1824 hospitals. Within each case-mix stratum, survival curves of the patients
      admitted to hospitals in each risk-standardized mortality rate quintile separated
      within the first 30 days and then remained parallel over 17 years of follow-up.
      Estimated life expectancy declined as hospital risk-standardized mortality rate
      quintile increased. On average, patients treated at high-performing hospitals
      lived between 0.74 and 1.14 years longer, depending on hospital case mix, than
      patients treated at low-performing hospitals. When 30-day survivors were examined
      separately, there was no significant difference in unadjusted or adjusted life
      expectancy across hospital risk-standardized mortality rate quintiles.
      CONCLUSIONS: In this study, patients admitted to high-performing hospitals after
      acute myocardial infarction had longer life expectancies than patients treated in
      low-performing hospitals. This survival benefit occurred in the first 30 days and
      persisted over the long term. (Funded by the National Heart, Lung, and Blood
      Institute and the National Institute of General Medical Sciences Medical
      Scientist Training Program.).

PMID- 27705250
TI  - Placenta Increta.

PMID- 27705251
TI  - Progress in Myeloma - A Monoclonal Breakthrough.

PMID- 27705252
TI  - Vaccine Refusal Revisited - The Limits of Public Health Persuasion and Coercion.

PMID- 27705253
TI  - Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.

PMID- 27705254
TI  - Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.

PMID- 27705255
TI  - Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.

PMID- 27705256
TI  - Data Monitoring Committees - Expect the Unexpected.

PMID- 27705257
TI  - State of Telehealth.

PMID- 27705258
TI  - State of Telehealth.

PMID- 27705259
TI  - Measles Elimination - Using Outbreaks to Identify and Close Immunity Gaps.

PMID- 27705261
TI  - Diabetic Sensory and Motor Neuropathy.

PMID- 27705260
TI  - Testing Limits.

PMID- 27705262
TI  - Olanzapine for Chemotherapy-Induced Nausea and Vomiting.

PMID- 27705265
TI  - Polycystic Ovary Syndrome.

PMID- 27705263
TI  - Olanzapine for Chemotherapy-Induced Nausea and Vomiting.

PMID- 27705264
TI  - Polycystic Ovary Syndrome.

PMID- 27705266
TI  - Polycystic Ovary Syndrome.

PMID- 27705268
TI  - Worms in the Eye.

PMID- 27705269
TI  - The Health Effects of Electronic Cigarettes.

PMID- 27705271
TI  - Explosion Injuries from E-Cigarettes.

PMID- 27705270
TI  - A Measles Outbreak in an Underimmunized Amish Community in Ohio.
AB  - BACKGROUND: Although measles was eliminated in the United States in 2000,
      importations of the virus continue to cause outbreaks. We describe the
      epidemiologic features of an outbreak of measles that originated from two
      unvaccinated Amish men in whom measles was incubating at the time of their return
      to the United States from the Philippines and explore the effect of public health
      responses on limiting the spread of measles. METHODS: We performed descriptive
      analyses of data on demographic characteristics, clinical and laboratory
      evaluations, and vaccination coverage. RESULTS: From March 24, 2014, through July
      23, 2014, a total of 383 outbreak-related cases of measles were reported in nine
      counties in Ohio. The median age of case patients was 15 years (range, <1 to 53);
      a total of 178 of the case patients (46%) were female, and 340 (89%) were
      unvaccinated. Transmission took place primarily within households (68% of cases).
      The virus strain was genotype D9, which was circulating in the Philippines at the
      time of the reporting period. Measles-mumps-rubella (MMR) vaccination coverage
      with at least a single dose was estimated to be 14% in affected Amish households
      and more than 88% in the general (non-Amish) Ohio community. Containment efforts
      included isolation of case patients, quarantine of susceptible persons, and
      administration of the MMR vaccine to more than 10,000 persons. The spread of
      measles was limited almost exclusively to the Amish community (accounting for 99%
      of case patients) and affected only approximately 1% of the estimated 32,630
      Amish persons in the settlement. CONCLUSIONS: The key epidemiologic features of a
      measles outbreak in the Amish community in Ohio were transmission primarily
      within households, the small proportion of Amish people affected, and the large
      number of people in the Amish community who sought vaccination. As a result of
      targeted containment efforts, and high baseline coverage in the general
      community, there was limited spread beyond the Amish community. (Funded by the
      Ohio Department of Health and the Centers for Disease Control and Prevention.).

PMID- 27705272
TI  - Past as Prologue - Presidential Politics and Health Policy.

PMID- 27705385
TI  - Mapping Discrimination Experienced by Indonesian Trans* FtM Persons.
AB  - This work sought to document how Indonesian trans* FtM persons experienced
      discrimination across the interlinked domains of social networks, religious and
      educational institutions, employment and the workplace, and health care
      institutions. Objectives were (1) to map the discrimination experienced by trans*
      FtM individuals in Indonesia, and (2) to establish the specific priorities of the
      Indonesian trans* FtM community. In-depth interviews, focus groups, and
      participant observation was used involving 14 respondents. Findings revealed that
      respondents experienced othering through rejection, misidentification,
      harassment, "correction," and bureaucratic discrimination across the five
      preestablished domains. Health care and a lack of information emerged as areas of
      particular concern for respondents. This work calls for health care that is
      sensitive to the needs of trans* FtM people coupled with high-quality information
      to alleviate the cycles through which discrimination is sustained.

PMID- 27705534
TI  - Can Motor Proficiency in Preschool Age Affect Physical Activity in Adolescence?
AB  - BACKGROUND: This study investigated if motor proficiency (MP) in preschool age
      associate with physical activity (PA) in adolescence. METHODS: In 2004, the
      Bruininks-Oseretsky Test of Motor Proficiency-Short Form (BOTMP-SF) (7) was
      administered to 413 children, aged 4-6 years, who were classified to MP groups
      according to their BOTMP-SF total score (TS). In 2014, the PA of 106 former
      participants (47 boys, 59 girls) was measured with Omron pedometers. MP [three
      (high; above average; average)] * gender (two) ANOVA and Bonferroni tests were
      computed on average of steps/week. RESULTS: A significant interaction between the
      two factors was revealed (F = 15.27, p < .001, eta2=.153), indicating that MP
      influenced male and female PA differently. Only in average MP group, males
      presented higher PA than females, whereas there were no differences between the
      two genders in the higher MP groups. Moreover, the only significant difference in
      PA among male groups was that between high and above average MP groups, while in
      females there were significant differences among all groups. CONCLUSION: High MP
      at preschool age positively associated with the PA in adolescence, especially in
      females. Emphasis on the development of proficient young movers might be
      beneficial for lifelong PA.

PMID- 27705533
TI  - Personality and Defense Styles: Clinical Specificities and Predictive Factors of
      Alcohol Use Disorder in Women.
AB  - This study investigated personality traits and defense styles in order to
      determine clinical specificities and predictive factors of alcohol use disorders
      (AUDs) in women. A female sample, composed of AUD outpatients (n = 48) and a
      control group (n = 50), completed a sociodemographic self-report and
      questionnaires assessing personality traits (BFI), defense mechanisms and defense
      styles (DSQ-40). Comparative and correlational analyses, as well as univariate
      and multivariate logistic regressions, were performed. AUD women presented with
      higher neuroticism and lower extraversion and conscientiousness. They used less
      mature and more neurotic and immature defense styles than the control group.
      Concerning personality traits, high neuroticism and lower conscientiousness were
      predictive of AUD, as well as low mature, high neurotic, and immature defense
      styles. Including personality traits and defense styles in a logistic model, high
      neuroticism was the only AUD predictive factor. AUD women presented clinical
      specificities and predictive factors in personality traits and defense styles
      that must be taken into account in AUD studies. Implications for specific
      treatment for women are discussed.

PMID- 27705535
TI  - Validity of Skinfold Equations, Against Dual-Energy X-Ray Absorptiometry, in
      Predicting Body Composition in Adolescent Pentathletes.
AB  - PURPOSE: Body composition of adolescent athletes is often evaluated
      scientifically and in sports by using reference equations developed from
      nonathlete adolescent populations. The aim of this study was to analyze the
      validity of predictive equations based on skinfold measurements, as compared with
      dual-energy X-ray absorptiometry (DXA), to estimate body fat in adolescent modern
      pentathlon athletes. METHODS: 51 athletes, 27 male (mean age = 15.1 years;
      standard deviation, SD = 1.5 years) and 24 female (mean age = 14.2 years; SD =
      2.5 years), were assessed using DXA, anthropometric parameters, sports practice
      anamnesis, and pubertal stages. Agreement between methods was tested with
      boxplots of mean comparisons using Student's t test (p < .05), and Bland-Altman
      plots. RESULTS: The body density equations of Durnin & Rahaman (1967) and Durnin
      & Womersley (1974) showed better agreement with DXA than the other predictive
      equations, for both females (difference between means=-2.03; 2SD = 8.44) and
      males (difference between means = 0.98; 2SD = 7.30). There were no mean
      differences between these equations and the reference method (DXA; p > .05), but
      they did display high variability (2SD). CONCLUSION: The high variability among
      results indicated imprecision. Predictive skinfold equations developed for
      nonathlete adolescents do not offer good validity for modern adolescent
      pentathlon athletes, and should be avoided.

PMID- 27705267
TI  - Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.
AB  - BACKGROUND: Daratumumab showed promising efficacy alone and with lenalidomide and
      dexamethasone in a phase 1-2 study involving patients with relapsed or refractory
      multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 569
      patients with multiple myeloma who had received one or more previous lines of
      therapy to receive lenalidomide and dexamethasone either alone (control group) or
      in combination with daratumumab (daratumumab group). The primary end point was
      progression-free survival. RESULTS: At a median follow-up of 13.5 months in a
      protocol-specified interim analysis, 169 events of disease progression or death
      were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of
      283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval
      [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate
      of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the
      daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control
      group. A significantly higher rate of overall response was observed in the
      daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a
      higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the
      daratumumab group, 22.4% of the patients had results below the threshold for
      minimal residual disease (1 tumor cell per 105 white cells), as compared with
      4.6% of those in the control group (P<0.001); results below the threshold for
      minimal residual disease were associated with improved outcomes. The most common
      adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the
      patients in the daratumumab group vs. 37.0% of those in the control group),
      thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%).
      Daratumumab-associated infusion-related reactions occurred in 47.7% of the
      patients and were mostly of grade 1 or 2. CONCLUSIONS: The addition of
      daratumumab to lenalidomide and dexamethasone significantly lengthened
      progression-free survival among patients with relapsed or refractory multiple
      myeloma. Daratumumab was associated with infusion-related reactions and a higher
      rate of neutropenia than the control therapy. (Funded by Janssen Research and
      Development; POLLUX ClinicalTrials.gov number, NCT02076009 .).

PMID- 27705537
TI  - A Longitudinal Study of Physical Fitness in Elite Junior Tennis Players.
AB  - PURPOSE: To analyze how physical fitness (PF) improves in elite junior tennis
      players related to age, maturity, and performance level. METHODS: Elite junior
      tennis players (n = 113 boys, n = 83 girls) divided by performance level were
      monitored longitudinally from U14 to U16. Maturity, upper and lower-body power,
      speed, and agility were measured during subsequent competitive seasons.
      Improvement was analyzed per sex using multilevel analysis. RESULTS: PF
      components for boys and girls improved over age (U14-U16) (ES .53-.97). In boys,
      the more mature boys outscored the less mature boys in upper and lower-body power
      from U14-U16. In girls, high-ranked girls outscored lower-ranked girls on lower
      body power, speed, and agility (U14-U16) (p < .05). CONCLUSION: Boys and girls
      improved on all PF components during U14-U16. In boys, power was related to
      maturity. In girls, lower-body power, speed, and agility were related to tennis
      performance. This has important implications for talent development.

PMID- 27705538
TI  - The Adolescent Athlete: A Developmental Approach to Injury Risk.
AB  - With the advent of long-term athlete development programs and early sport
      specialization, the training of elite athletes now spans the period of
      adolescence. Adolescence represents a period of physical, psychosocial and
      cognitive development, but also a time of physical and psychological
      vulnerability. Changes in skeletal and physiological attributes coincide with an
      increased risk of sport related injury. A window of vulnerability is shaped by
      the properties of the musculoskeletal system, the influence of pubertal hormones
      and the lag time between physical and cognitive development. This article aims to
      challenge the assumption of adolescence as a time of increased vigor alone, by
      highlighting the presence of specific vulnerabilities, and proposing that the
      hormonal, musculoskeletal, and neurocognitive changes of adolescence may
      represent intrinsic risk factors for sport related injury.

PMID- 27705539
TI  - Distribution and Diversity of Bartonella washoensis Strains in Ground Squirrels
      from California and Their Potential Link to Human Cases.
AB  - We investigated the prevalence of Bartonella washoensis in California ground
      squirrels (Otospermophilus beecheyi) and their fleas from parks and campgrounds
      located in seven counties of California. Ninety-seven of 140 (69.3%) ground
      squirrels were culture positive and the infection prevalence by location ranged
      from 25% to 100%. In fleas, 60 of 194 (30.9%) Oropsylla montana were found to
      harbor Bartonella spp. when screened using citrate synthase (gltA) specific
      primers, whereas Bartonella DNA was not found in two other flea species,
      Hoplopsyllus anomalus (n = 86) and Echidnophaga gallinacea (n = 6). The
      prevalence of B. washoensis in O. montana by location ranged from 0% to 58.8%. A
      majority of the gltA sequences (92.0%) recovered from ground squirrels and fleas
      were closely related (similarity 99.4-100%) to one of two previously described
      strains isolated from human patients, B. washoensis NVH1 (myocarditis case in
      Nevada) and B. washoensis 08S-0475 (meningitis case in California). The results
      from this study support the supposition that O. beecheyi and the flea, O.
      montana, serve as a vertebrate reservoir and a vector, respectively, of zoonotic
      B. washoensis in California.

PMID- 27705536
TI  - Physiological Adaptations following Resistance Training in Youth Athletes-A
      Narrative Review.
AB  - PURPOSE: To understand the mechanisms for the effects of resistance training on
      functional parameters, and to assess the injury risk of the involved tissues, it
      is necessary to examine the underlying morphological and structural changes of
      the respective tissues. METHODS: The presented information on physiological
      adaptations have been deduced from cross-sectional studies comparing youth
      athletes with controls and children with adults as well as from longitudinal
      studies examining the effects of resistance training in untrained children and
      adolescents and in youth athletes. RESULTS: The evidence indicates, that training
      induced changes in motor performance rely partly on enhanced neuromuscular
      control, and partly on morphological adaptation of muscles and tendons, such as
      changes in muscle, muscle fiber and tendon cross-sectional area, muscle
      composition, and tendon material properties, with the bone also adapting by
      increasing bone mineral content and cortical area. CONCLUSION: Although the
      training induced adaptations of the investigated tissues follows similar
      principles in children as in adults, the magnitude of the adaptive response
      appears to be more subtle. As studies investigating physiological adaptation in
      youth athletes are sparse, more research in this area is warranted to elucidate
      the specific physiological stimulus-response relationship necessary for effective
      training programs and injury prevention.

PMID- 27705540
TI  - Periparturient characteristics of mares and their foals on a New Zealand
      Thoroughbred stud farm.
AB  - AIMS: To describe selected periparturient variables in a sample of Thoroughbred
      mares and their foals on a commercial stud farm in New Zealand. METHODS: Data
      were collected for 969 foaling records, from 592 mares, by foaling attendants
      from one Thoroughbred stud farm in the Waikato region of New Zealand for the
      breeding seasons 2008-2013, inclusive, and collated retrospectively. The
      associations between mare- and foal-level variables and gestation length, time of
      birth (expressed as the number of hours after midday), fetal membrane retention
      time, time for the foal to stand and suckle after birth, and foal mortality were
      quantified using linear and logistic regression models. RESULTS: Mean gestation
      length for mares in this study was 350 (min 296, max 429) days, and was shorter
      for filly foals (348 (min 296, max 429) days) compared with colt foals (350 (min
      310, max 404) days) (p=0.001). Overall, 517/968 (53%) foalings occurred between
      19:00 and 01:00 and 212/968 (22%) foalings occurred during daylight. Overall,
      815/855 (95%) expelled their fetal membranes within 4 hours of parturition. The
      mean interval from birth to standing and to suckling was shorter (p<0.001) for
      filly foals than colts by 13 (95% CI=9-17) and 17 (95% CI=8-26) minutes,
      respectively. Dystocia was reported for 81/968 (8.4%) foalings with relative
      fetal oversize being the most common cause (36/81 (44%) cases). Perinatal foal
      death was recorded for 26/966 (2.7%) foalings. The odds of foal mortality
      decreased with increasing length of gestation (p=0.027), and were greater for
      colt than filly foals (p=0.042) and when dystocia was reported (p<0.001).
      CONCLUSIONS: Gestation length was influenced by the sex of the foal, as was the
      time taken for the foal to stand and suckle after birth. One fifth of mares
      foaled during daylight hours. The majority of mares in this study population
      expelled their fetal membranes within 4 hours of foaling. CLINICAL RELEVANCE:
      Accurate measures for periparturient behaviour can be important in the management
      of mares and newborn foals. Clinically relevant differences appear to exist
      between mares and foals in New Zealand and those in the Northern Hemisphere for
      some key parameters, likely as a result of differences in management and
      environment. The results of this study suggest that mares should be considered to
      have retained their membranes if not passed within 4 hours of parturition.

PMID- 27705541
TI  - Perceived Cross-Orientation Infidelity: Heterosexual Perceptions of Same-Sex
      Cheating in Exclusive Relationships.
AB  - For individuals in exclusive romantic relationships, the dynamics of sexual
      experimentation are nuanced. Extradyadic behavior outside of a relationship may
      be perceived as cheating or infidelity, with much of those perceptions driven by
      the biological sex of the perceiver. This study significantly reframes seminal
      research on perceptions of cheating with third-party friends by Kruger et al.
      (2013), to further nuance an evolutionary threat-based model. In doing so, this
      furthers our understanding of the associated perceptions of individuals in
      heterosexual relationships when confronted by partners' cheating with their same
      sex cross-orientation friends. Results indicate that perceptions of same-sex
      infidelity vary widely depending on the nature of the behaviors, with decreasing
      attribution given to sexual and erotic behaviors, close relational behaviors, and
      casual social interaction behaviors, respectively. Implications are discussed for
      a variety of sexual communities, as well as the impact of gender and relational
      status on perceptions of infidelity.

PMID- 27705542
TI  - Shifting Away from a Deficit Model of Health Literacy.

PMID- 27705543
TI  - Environmental risk of mesothelioma in the United States: An emerging concern
      epidemiological issues.
AB  - Despite predictions of decline in mesothelioma following the ban of asbestos in
      most industrial countries, the incidence is still increasing globally,
      particularly in women. Because occupational exposure to asbestos is the main
      cause of mesothelioma, it occurs four- to eightfold more frequently in men than
      women, at a median age of 74 years. When mesothelioma is due to an environmental
      exposure, the M:F sex ratio is 1:1 and the median age at diagnosis is ~60 years.
      Studying environmental risk of mesothelioma is challenging because of the long
      latency period and small numbers, and because this type of exposure is
      involuntary and unknown. Individual-based methods cannot be used, and new
      approaches need to be found. To better understand the most recent trends of
      mesothelioma in the United States, all mesothelioma deaths reported to the
      Centers for Disease Control and Prevention (CDC) during 1999-2010 were analyzed.
      Among all mesothelioma deaths in the United States, the 1920s birth cohort
      significantly predominated, and the proportion of younger cohorts constantly
      decreased with time, suggesting a decline in occupational exposure in these
      cohorts. The M:F mesothelioma sex ratio fell with time, suggesting an increased
      proportion of environmental cases. Environmental exposures occur in specific
      geographic areas. At the large scale of a state, mesotheliomas related to
      environmental exposure are diluted among occupational cases. The spatial analysis
      at a smaller scale, such as county, enables detection of areas with higher
      proportions of female and young mesothelioma cases, thus indicating possible
      environmental exposure, where geological and environmental investigations need to
      be carried out.

PMID- 27705544
TI  - Malignant mesothelioma in Australia 2015: Current incidence and asbestos exposure
      trends.
AB  - Australia is known to have had the highest per-capita asbestos consumption level
      of any nation, reaching a peak in the 1970s. Although crocidolite was effectively
      banned in the late 1960s, and amosite use ceased in the mid 1980s, a complete
      asbestos ban was not implemented until 2003. This resulted in an epidemic of
      asbestos-related disease, which has only now reached its peak. Between 1982 and
      2011, 13,036 individuals were newly diagnosed with malignant mesothelioma, with
      690 diagnosed in 2011. A further 778 cases were identified between 1945 and 1981
      from retrospective searches and the first 2 years of the Australian Mesothelioma
      Program. The age-standardized malignant mesothelioma incidence rate has leveled
      off in the last 10 years (2.8 per 100,000 in 2011). There has been a marked
      increase over time in the age-specific incidence rates for individuals aged 75
      years or older. Data from the current Australian Mesothelioma Registry on
      asbestos exposure history in Australia is available for 449 subjects diagnosed
      between July 1, 2010, and April 1, 2015. This asbestos exposure history data show
      that 60% (n = 268) of cases had probable or possible occupational asbestos
      exposure, with trade-based jobs being the most frequent sources of occupational
      asbestos exposure. In addition, out of the 449 cases, 377 were recorded as having
      probable or possible nonoccupational asbestos exposure. Continuous vigilance
      toward changes over time in the settings in which people are exposed to asbestos
      and in the descriptive epidemiology of malignant mesothelioma is recommended to
      enable a comprehensive understanding of the current and future impact of asbestos
      related diseases in Australia.

PMID- 27705546
TI  - Five years update on relationships between malignant pleural mesothelioma and
      exposure to asbestos and other elongated mineral particles.
AB  - Despite the reduction of global asbestos consumption and production due to the
      ban or restriction of asbestos uses in more than 50 countries since the 1970s,
      malignant mesothelioma remains a disease of concern. Asbestos is still used,
      imported, and exported in several countries, and the number of mesothelioma
      deaths may be expected to increase in the next decades in these countries.
      Asbestos exposure is the main risk factor for malignant pleural mesothelioma, but
      other types of exposures are linked to the occurrence of this type of cancer.
      Although recent treatments improve the quality of life of patients with
      mesothelioma, malignant pleural mesothelioma remains an aggressive disease.
      Recent treatments have not resulted in appreciable improvement in survival, and
      thus development of more efficient therapies is urgently needed. The development
      of novel therapeutic strategies is dependent on our level of knowledge of the
      physiopathological and molecular changes that mesothelial cells acquired during
      the neoplastic process. During the past 5 years, new findings have been published
      on the etiology, epidemiology, molecular changes, and innovative treatments of
      malignant pleural mesothelioma. This review aims to update the findings of recent
      investigations on etiology, epidemiology, and molecular changes with a focus on
      (1) attributable risk of asbestos exposure in men and women and (2) coexposure to
      other minerals and other elongated mineral particles or high aspect ratio
      nanoparticles. Recent data obtained on genomic and gene alterations, pathways
      deregulations, and predisposing factors are summarized.

PMID- 27705547
TI  - Pathology analysis for mesothelioma study in the United Kingdom: Current practice
      and historical development.
AB  - Following up on the largest case-control study of malignant mesothelioma yet
      performed, investigators at the London School of Hygiene and Tropical Medicine
      assessed 1732 male and 670 female cases as of May 2013. Epidemiological findings
      of a subset of these were published previously, excluding patients who died or
      who refused to be interviewed. Pathology reports were collected for subjects,
      including those both eligible and ineligible for epidemiology study based on
      vital status. The current investigation examined 860 cases having pathology
      reports available. Sixty-one cases were diagnosed using cytology only, often with
      equivocal diagnoses, while 799 reported at least a biopsy of the tumor. Of these,
      748 had pathology sufficiently detailed for evaluation. These reports were
      examined for basis of diagnosis, differences between study cases and ineligible
      cases, pathology characteristics, and immunohistochemical and other tests used.
      The most prominent subtype was epithelioid (64% of study cases but only 49% of
      ineligible cases). Biphasic subtype was present in 10% of study cases and 16% of
      those ineligible. Sarcomatoid subtype was present in 7% of study cases and 19% of
      ineligible cases, most of whom died. Twelve percent of study cases displayed no
      specified subtype, versus 7% of ineligible cases. Of recorded immunohistochemical
      stains specific for mesothelial cell origin, calretinin (95%) and CK 5/6 or CK5
      alone (84%) were by far the most common. Calretinin and CK 5/6 or CK 5 alone were
      also most sensitive and positive in 92% of cases presenting with surgical
      pathology report. Ninety percent of cases had at least one immunohistochemical
      marker for possible lung carcinoma applied, with BER-Ep4 and TTF-1 the most
      frequent at 68% and CEA at 58%. TTF-1 and CEA were positive in 1% or less of
      cases. Patterns of use and positive and negative results for each of these as
      well as other immunohistochemical stains are presented and discussed, along with
      a brief historical description of their development and use. Possible effects of
      the pathologic analysis on the results of previously published and future
      epidemiological studies are discussed.

PMID- 27705549
TI  - Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the
      United States.
AB  - Mesothelioma, a rare tumor, is highly correlated with asbestos exposure.
      Mesothelioma, similar to all asbestos-related diseases, is dose/intensity
      dependent to some degree, and studies showed the risk of mesothelioma rises with
      cumulative exposures. Multiple processes occur in an individual before
      mesothelioma occurs. The impact of mesothelioma in the United States has been
      continuous over the last half century, claiming between 2,000 and 3,000 lives
      each year. Mesothelioma is a preventable tumor that is more frequently reported
      as associated with asbestos exposure among men than women. However, the rate of
      asbestos-associated mesothelioma is on the rise among women due to better
      investigation into their histories of asbestos exposure. It is of interest that
      investigators detected asbestos-associated cases of mesothelioma in women from
      nonoccupational sources-that is, bystander, incidental, or take-home exposures.
      It is postulated that asbestos-associated mesotheliomas, in both men and women,
      are likely underreported. However, with the implementation of the most recent ICD
      10 coding system, the correlation of mesothelioma with asbestos exposure is
      expected to rise to approximately 80% in the United States. This study examined
      the demographic and etiological nature of asbestos-related mesothelioma.

PMID- 27705548
TI  - Quantitative structure-mesothelioma potency model optimization for complex
      mixtures of elongated particles in rat pleura: A retrospective study.
AB  - Cancer potencies of mineral and synthetic elongated particle mixtures, including
      asbestos fibers, are influenced by changes in fiber dose composition,
      bioavailability, and biodurability in combination with relevant cytotoxic dose
      response relationships. An extensive rat intrapleural dose characterization data
      set with a wide variety of elongated particles physicochemical properties
      facilitated statistical analyses of pleural mesothelioma response data combined
      from several studies for evaluation of alternative dose-response models.
      Utilizing logistic regression of individual elongated particle dimensional
      variations within each test sample, four major findings emerged: (1) Mild acid
      leaching provides superior prediction of tumor incidence compared to samples that
      were not leached; (2) sum of the elongated particle surface areas from mildly
      acid-leached samples provides the optimum holistic dose-response model; (3)
      progressive removal of dose associated with very short and/or thin elongated
      particles significantly degrades the resultant particle count and surface area
      dose-based predictive model fits; and (4) alternative biologically plausible
      model adjustments provide evidence for reduced potency of elongated particles
      with aspect ratios less than 8 and lengths greater than 80 um. Regardless of
      these adjustments, the optimum predictive models strongly incorporate potency
      attributable to abundant short elongated particles in proportion to their surface
      area. Transmission electron microscopy analyses of low-temperature-ashed pleural
      membrane and lung tissues 5.5 mo post intrapleural exposures do not support
      hypotheses that short elongated particles that reach the pleural space are
      rapidly eliminated. Low-aspect-ratio elongated particles were still abundant in
      pleural membrane tissues but may have reduced potencies due to aggregation
      tendencies and therefore lower potential for intracellular presence.

PMID- 27705550
TI  - Tyler asbestos workers: A mortality update in a cohort exposed to amosite.
AB  - The Tyler asbestos plant produced pipe insulation from 1954 to 1972 and
      exclusively used amosite asbestos. There were 1130 former workers of this plant
      during the period of operation. A death certificate mortality analysis was
      published regarding this plant in 1998 for the period through 1993. This study
      represents an update of the mortality analysis with additional certificates
      collected for deaths occurring through 2011.Searches of the National Death Index
      database were conducted in 2004 and again in 2013. At the time of the latter
      search, only deaths occurring through 2011 were available. In total, 265 distinct
      additional death certificates were secured and added to 304 available from the
      original study. After the new certificates were coded (ICD-9), data were analyzed
      using the Centers for Disease Control and Prevention Life Table Analysis System
      (LTAS) and standard mortality ratios (SMR) generated with 95% confidence limits
      (CL). LTAS constructs cause-specific mortality rates by age, gender, race, and
      person-time at risk, and compares observed rates with a referent population in
      order to derive SMR. A significant excess number of deaths due to nonmalignant
      respiratory disease (asbestosis) and from select malignant neoplasms were
      identified. There were in total 23 mesothelioma deaths (4% of deaths), with 16
      pleural and 7 peritoneal. The SMR for malignant neoplasms of the trachea,
      bronchus, and lung was 244 (with 95% CL 196, 300), suggesting that exposed
      workers from this cohort were nearly 2.5-fold (244 %) more likely to die from
      this cause as the general referent population. The analysis also showed that
      exposures of short duration (<6 mo) produced significantly elevated SMR for all
      respiratory cancers, lung cancer, and pleural mesothelioma. There was a
      significant difference in median duration of exposure for mesothelioma types,
      confirming association of peritoneal mesothelioma with longer duration of
      exposure. Deaths due to intestinal cancer (predominantly colon; not including
      rectum) were also found in excess. The mortality experience of the Tyler cohort
      continues to be followed with great interest, given the exclusivity of exposure
      to amosite. Data confirm the inherent pathogenicity of this fiber type for
      nonmalignant disease as well as select cancers, particularly relevant given the
      importance of this amphibole's use in the United States.

PMID- 27705551
TI  - Preface: Respirable elongated mineral particles and human health-Revisited.

PMID- 27705608
TI  - Simple Technique of Circular Stapled Anastomosis in Ivor Lewis Esophagectomy.
AB  - BACKGROUND: Advent of minimally-invasive esophagectomy necessitated the
      incorporation of stapled anastomotic techniques especially for intrathoracic
      anastomosis. We present our approach to the Ivor Lewis esophagectomy highlighting
      a simple modification in the anastomotic technique and review our experience with
      anastomotic outcomes. METHODS: With IRB approval, patients who underwent Ivor
      Lewis esophagectomy with circular-stapled end-to-end anastomosis (EEA) were
      identified, divided into three equal sequential cohorts (A, B, and C), and
      compared for perioperative outcome. Cohorts were divided in a chronological order
      to have equal number of patients in each group. RESULTS: Seventy-five patients
      underwent Ivor Lewis esophagectomy with circular stapled (EEA-25/28) anastomosis.
      Group A had longer median postoperative hospital stay and median postoperative
      ICU stay compared to Groups B and C. Ten patients (13%) had anastomotic leak-one
      patient required redo-anastomosis and other patients were managed with endoscopic
      interventions. There was significant decrease in rate of anastomotic leak with
      experience (8 versus 1 versus 1, P = .004). There were two perioperative deaths,
      one each in Groups A and C, including one death due to anastomotic leak (Group
      A). CONCLUSION: Use of simple modifications to stapled EEA, as described here,
      has led to decrease in anastomotic leaks following Ivor Lewis esophagectomy.

PMID- 27705545
TI  - Investigating palygorskite's role in the development of mesothelioma in southern
      Nevada: Insights into fiber-induced carcinogenicity.
AB  - Similar to asbestos fibers, nonregulated mineral fibers can cause malignant
      mesothelioma (MM). Recently, increased proportions of women and young individuals
      with MM were identified in southern Nevada, suggesting that environmental
      exposure to carcinogenic fibers was causing the development of MM. Palygorskite,
      a fibrous silicate mineral with a history of possible carcinogenicity, is
      abundant in southern Nevada. In this study, our aim was to determine whether
      palygorskite was contributing to the development of MM in southern Nevada. While
      palygorskite, in vitro, displayed some cytotoxicity toward primary human
      mesothelial (HM) cells and reduced their viability, the effects were roughly half
      of those observed when using similar amounts of crocidolite asbestos. No Balb/c
      (0/19) or MexTAg (0/18) mice injected with palygorskite developed MM, while 3/16
      Balb/c and 13/14 MexTAg mice injected with crocidolite did. Lack of MM
      development was associated with a decreased acute inflammatory response, as
      injection of palygorskite resulted in lower percentages of macrophages (p = .006)
      and neutrophils (p = .02) in the peritoneal cavity 3 d after exposure compared to
      injection of crocidolite. Additionally, compared to mice injected with
      crocidolite, palygorskite-injected mice had lower percentages of M2 (tumor
      promoting) macrophages (p = .008) in their peritoneal cavities when exposed to
      fiber for several weeks. Our study indicates that palygorskite found in the
      environment in southern Nevada does not cause MM in mice, seemingly because
      palygorskite, in vivo, fails to elicit inflammation that is associated with MM
      development. Therefore, palygorskite is not a likely contributor to the MM cases
      observed in southern Nevada.

PMID- 27705725
TI  - Prostate, Breast and Ovarian Cancer Genetic Risk Assessment: Connecting the Dots.

PMID- 27705726
TI  - Legends in Urology.

PMID- 27705609
TI  - Emergence of Oxacillinases in Environmental Carbapenem-Resistant Acinetobacter
      baumannii Associated with Clinical Isolates.
AB  - Six carbapenem-resistant isolates of Acinetobacter baumannii were recovered from
      untreated and treated municipal wastewater of the capital city of Zagreb,
      Croatia. Molecular identification of environmental isolates of A. baumannii was
      performed by amplification, sequencing, and phylogenetic analyses of rpoB gene.
      The presence of blaOXA genes encoding OXA-type carbapenemases (OXA-51-like, OXA
      23, and OXA-40-like) was confirmed by multiplex PCR and sequencing. Phylogenetic
      analyses corroborated the affiliation of detected blaOXA genes to three different
      clusters and showed association of environmental OXAs with those described from
      clinical isolates. This result suggests that isolates recovered from municipal
      wastewater are most probably of clinical origin. Furthermore, the presence of OXA
      40-like (OXA-72) in an environmental A. baumannii isolate is reported for the
      first time. Persistence of A. baumannii harboring the clinically important OXAs
      in the wastewater treatment process poses a potentially significant source for
      horizontal gene transfer and implications for wider spread of antibiotic
      resistance genes.

PMID- 27705664
TI  - Genetic Mapping of Stem Rust Resistance to Puccinia graminis f. sp. tritici Race
      TRTTF in the Canadian Wheat Cultivar Harvest.
AB  - Stem rust, caused by Puccinia graminis f. sp. tritici, is a destructive disease
      of wheat that can be controlled by deploying effective stem rust resistance (Sr)
      genes. Highly virulent races of P. graminis f. sp. tritici in Africa have been
      detected and characterized. These include race TRTTF and the Ug99 group of races
      such as TTKSK. Several Canadian and U.S. spring wheat cultivars, including the
      widely grown Canadian cultivar 'Harvest', are resistant to TRTTF. However, the
      genetic basis of resistance to TRTTF in Canadian and U.S. spring wheat cultivars
      is unknown. The objectives of this study were to determine the number of Sr genes
      involved in TRTTF resistance in Harvest, genetically map the resistance with DNA
      markers, and use markers to assess the distribution of that resistance in a panel
      of Canadian cultivars. A doubled haploid (DH) population was produced from the
      cross LMPG-6S/Harvest. The DH population was tested with race TRTTF at the
      seedling stage. Of 92 DH progeny evaluated, 46 were resistant and 46 were
      susceptible which perfectly fit a 1:1 ratio indicating a single Sr gene was
      responsible for conferring resistance to TRTTF in Harvest. Mapping with single
      nucleotide polymorphism (SNP) and simple sequence repeat (SSR) markers placed the
      resistance gene distally on the chromosome 6AS genetic map, which corresponded to
      the location reported for Sr8. SSR marker gwm459 and 30 cosegregating SNP markers
      showed the closest linkage, mapping 2.2 cM proximal to the Sr gene. Gene Sr8a
      confers resistance to TRTTF and may account for the resistance in Harvest.
      Testing a panel of Canadian wheat cultivars with four SNP markers closely linked
      to resistance to TRTTF suggested that the resistance present in Harvest is
      present in many Canadian cultivars. Two of these SNP markers were also predictive
      of TRTTF resistance in a panel of 241 spring wheat lines from the United States,
      Canada, and Mexico.

PMID- 27705727
TI  - Robotic versus laparoscopic radical nephrectomy: comparative analysis and cost
      considerations.
AB  - INTRODUCTION: Robotic-assisted laparoscopic radical nephrectomy (RRN) is an
      increasing utilized alternative to laparoscopic radical nephrectomy (LRN);
      however, there is a little data on comparative effectiveness and cost of these
      procedures. We analyzed perioperative outcomes and hospital charge difference
      among patients undergoing laparoscopic radical nephrectomy (LRN) and robotic
      radical nephrectomy (RRN). MATERIALS AND METHODS: Our institutional renal mass
      registry was queried for patients who underwent either LRN or RRN from 2010 to
      2014. Demographic, perioperative outcomes and hospital charge data were compared
      between surgical approaches. RESULTS: Overall, 319 minimally invasive radical
      nephrectomies were performed during the study period. Of these, 243 were LRN and
      76 were RRN. Patient demographic and tumor characteristics were similar between
      groups. Among operative characteristics, operative time (136 min versus 139 min,
      p = 0.531), intraoperative complications (2.8% versus 2.0%, p = 0.650), and
      length of stay (2 days versus 2 days, p = 0.745) were similar for LRN and RRN,
      respectively. Estimated blood loss (50 mL versus 100 mL, p = 0.041) and rate of
      conversion to an alternative surgical approach (1.0% versus 11.1%, p < 0.001)
      were higher in RRN. RRN cases were also more likely to include lymph node
      dissection (12.6% versus 24.2%, p = 0.031). Total charges trended higher for RRN
      but did not meet traditional levels of significance ($14,913 versus $16,265, p =
      0.171). CONCLUSIONS: RRN appears to be a clinically equivalent alternative to LRN
      with similar perioperative outcomes, albeit at greater hospital charges.

PMID- 27705728
TI  - Clinical variables and stone detection in patients with flank pain.
AB  - INTRODUCTION: Non-contrast CT (NCT) is commonly used to evaluate flank pain (FP).
      We sought to evaluate incidence of ureteral calculi on NCT in patients with FP,
      and to determine if clinical variables are associated with higher detection
      rates. MATERIALS AND METHODS: Retrospective review identified 613 patients
      undergoing NCT for FP. Patient clinical data, NCT findings, and intervention were
      analyzed. Focus was placed on variables commonly associated with urolithiasis
      (Vstone), comprising hematuria, nausea/vomiting, and prior stone history.
      Statistical analysis was performed to identify risk of ureteral stones based on
      number and type of Vstone. RESULTS: No stone disease was identified on NCT in 175
      patients (28.5%). NCT demonstrated 214 (35%), 72 (12%), and 152 (25%) patients
      with stones located in the kidney, ureter, or both, respectively. Only 33 (5%)
      patients had FP as their sole Vstone, with ureteral calculi identified in 6% of
      this cohort. The rate of ureteral calculi increased with more Vstone. Patients
      having all four Vstone were found to have the highest rate of ureteral stones
      (59%). Statistical analysis demonstrated a statistically significantly increased
      relative risk of stone formation given three or four Vstone when compared with FP
      alone. CONCLUSIONS: Whereas isolated FP is associated with a lower rate of
      ureteral calculus detection, a significant increased relative risk of ureteral
      calculus is seen in patients with additional clinical variables associated with
      stone disease. Accordingly, it may be possible to improve detection rates of
      ureteral stones through the use of additional clinical variables to guide NCT
      selection.

PMID- 27705730
TI  - Erectile function recovery after robotic-assisted radical prostatectomy (RARP):
      long term exhaustive analysis across all preoperative potency categories.
AB  - INTRODUCTION: To evaluate erectile function recovery following robotic-assisted
      radical prostatectomy (RARP) according to preoperative sexual health inventory
      for men (SHIM) score stratification. MATERIALS AND METHODS: We prospectively
      collected data on 250 consecutive patients who underwent RARP by a single surgeon
      between October 2006 and October 2012. Thirty-six patients were excluded because
      of lack of preoperative SHIM score. All patients had a minimum follow up of 2
      years. Patients were divided into four groups according to their preoperative
      SHIM score: group 1 with normal potency (SHIM 22-25), group 2 with mild ED (SHIM
      17-21), group 3 with mild-moderate ED (SHIM 12-16) and group 4 with moderate
      severe ED (SHIM 1-11). Patients were followed at 3, 6, 9, 12, 18, 24 months
      intervals and twice yearly thereafter. SHIM questionnaire and erection hardness
      scale (EHS) score were collected at each visit. Potency was defined as successful
      penetration during intercourse (EHS score 3-4) with or without phosphodiesterase
      type 5-inhibitor (PDE5-I). RESULTS: After exclusion, 214 patients were evaluated.
      The number of patients in group 1, 2, 3 and 4 were 95, 59, 26 and 34,
      respectively. At 3, 6, 9, 12, 18, 24 months, SHIM scores and potency rates were
      statistically different between groups 1 versus 2 versus 3 versus 4 (p < 0.01, at
      each time point). Patients in each group 1, 2 and 3 showed a statistically
      significant improvement in potency rates and SHIM scores at consecutive follow up
      visits up to 24 months (p < 0.01, for each potency group). Potency rates at 24
      months for groups 1 to 4 were 83.3%, 54.5%, 50.0%, and 20.7%, respectively (p <
      0.001). CONCLUSION: For proper patient counseling and better prediction of
      erectile function recovery after RARP, it is important to stratify patients
      according to preoperative SHIM scores. Setting realistic expectations may
      increase patient satisfaction.

PMID- 27705729
TI  - Urinalysis findings are not predictive of positive urine culture in patients with
      indwelling stents.
AB  - INTRODUCTION: Indwelling stents produce symptoms and urinalysis findings
      mimicking urinary tract infection (UTI). In this study, we investigated the
      correlation of urinalysis findings with urine culture in patients with indwelling
      ureteral stents. MATERIALS AND METHODS: All patients with ureteral stents who
      underwent stent removal in urology clinic from July 2013 to January 2015 and had
      urine culture available immediately prior to stent removal were included in this
      study. Urine culture results as well as age, gender, duration of indwelling
      stent, and reason for stent placement were collected. RESULTS: A total of 122
      patients were included in this study. The two most common reasons for ureteral
      stent placement included urolithiasis (65.6%) and renal transplant (22.1%). Red
      blood cell (RBC), leukocytes and nitrite were positive in 92.9%, 70.2% and 17.9%
      of urine samples respectively. Only 17 patients (13.9%) had positive urine
      culture. Although renal transplant patients had significantly longer duration of
      stent retention, no statistically significant difference was noted in rate of
      positive urine culture compared to urolithiasis patients (p = 1.0). Among
      patients with positive urine culture, 62.5% had resistant bacteria to common
      antibiotic treatments and two patients had yeast in urine culture (12.5%). The
      duration of stent retention did not correlate with bacterial resistance.
      Multivariate analysis failed to show significant correlation of gender, reason
      for stent, stent duration, RBC and nitrite with positive urine culture.
      CONCLUSIONS: Positive findings on urinalysis in patients with indwelling ureteral
      stent have poor correlation to positive urine culture and therefore the use of
      urine culture to diagnose UTI is warranted.

PMID- 27705731
TI  - Poor split renal function and age in adult patients with ureteropelvic junction
      obstruction do not impact functional outcomes of pyeloplasty.
AB  - INTRODUCTION: To examine if poor preoperative split renal function (SRF) and age
      influence pyeloplasty outcomes in adults with ureteropelvic junction obstruction
      (UPJO). MATERIALS AND METHODS: We retrospectively reviewed our pyeloplasty
      experience in adults with UPJO from 2004 to 2014. Patients with solitary kidneys
      or missing renal scans were excluded. Renal scans were performed at 6 weeks, 8
      months, and 20-24 months postoperatively. Demographics, operative approaches, and
      pre and postoperative SRF and diuretic half-times (T1/2) were obtained. Patients
      were stratified by preoperative SRF (<= or > 25%) and age. Cox regression
      analyses were performed to explore predictors for stability or improvement of
      SRF. RESULTS: A total of 139 patients met the study criteria: 15 and 124 with
      preoperative SRF <= 25% and > 25%, respectively. Median follow up was 11 months,
      12.9% of patients experienced worsening, 67.6% stability, and 19.4% improvement
      in SRF at last follow up. Median change in SRF was similar between groups;
      however, patients with lower preoperative SRF more frequently experienced
      improvement or worsening of SRF (p = 0.045). Failure rates (need for additional
      surgery) were comparable (p = 1.000). No significant differences were observed in
      SRF dynamicity when stratified by age (p = 0.120). On univariate Cox analysis,
      older age was predictive of stability or improvement in SRF across the entire
      cohort (HR 1.013, p = 0.016), while preoperative SRF was not (HR 1.007, p =
      0.429). CONCLUSIONS: Poor SRF (<= 25%) and age were not associated with worse
      outcomes after pyeloplasty for UPJO. Our results suggest that older adults with
      UPJO and patients with poor ipsilateral SRF should not be excluded from
      pyeloplasty.

PMID- 27705732
TI  - Infectious complications associated with the use of temporary prostatic urethral
      stents in patients with benign prostatic hyperplasia.
AB  - INTRODUCTION: To examine the infectious outcomes after the insertion of the
      temporary prostatic urethral stent (TPUS) in benign prostatic hyperplasia (BPH)
      patients. MATERIAL AND METHODS: Between November 2007 and September 2012, ninety
      TPUS were used in 33 patients with BPH at our institution. All patients had
      negative urine cultures prior to the first stent insertion. TPUS were sent for
      cultures at time of removal or exchange. Stents were removed at the time of
      definite surgical intervention, at 4-6 weeks, or when patients elected another
      course of treatment. Colonization was defined as asymptomatic positive stent
      culture. Infection was defined as symptomatic positive stent culture requiring
      treatment. Infection and colonization rates are reported. Logistic regression was
      used to examine the predictors of infection at any point. Predictors examined
      were age, body mass index, history of prostate cancer, diabetes mellitus,
      hyperlipidemia, coronary artery disease, neurologic disorder, erectile
      dysfunction and the sequence of stent placement. RESULTS: The majority of the
      subjects, 72% (24/33) had 1-2 stents, 9.0% (3/33) had 3-4 stents, 6.0% (2/33) had
      5-6 stents, and 12% (4/33) of patients had more than 6 stents. From the 69
      available culture results, the symptomatic infection rate was 16% (11/69) (95%
      CI: 8.2%-26.7%). The colonization rate was 58% (40/69) (95% CI: 45.5%-69.7%).
      None of the predictors examined were identified as a predictor of infection.
      There was no colonization detected when stents were removed in the first 20 days.
      CONCLUSION: Infection rates with TPUS in BPH patients are acceptable and early
      removal may prevent colonization.

PMID- 27705610
TI  - Supplements, nutrition, and alternative therapies for the treatment of traumatic
      brain injury.
AB  - Studies using traditional treatment strategies for mild traumatic brain injury
      (TBI) have produced limited clinical success. Interest in treatment for mild TBI
      is at an all time high due to its association with the development of chronic
      traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic
      options remain limited. Traditional pharmaceutical interventions have failed to
      transition to the clinic for the treatment of mild TBI. As such, many pre
      clinical studies are now implementing non-pharmaceutical therapies for TBI. These
      studies have demonstrated promise, particularly those that modulate secondary
      injury cascades activated after injury. Because no TBI therapy has been
      discovered for mild injury, researchers now look to pharmaceutical
      supplementation in an attempt to foster success in human clinical trials. Non
      traditional therapies, such as acupuncture and even music therapy are being
      considered to combat the neuropsychiatric symptoms of TBI. In this review, we
      highlight alternative approaches that have been studied in clinical and pre
      clinical studies of TBI, and other related forms of neural injury. The purpose of
      this review is to stimulate further investigation into novel and innovative
      approaches that can be used to treat the mechanisms and symptoms of mild TBI.

PMID- 27705733
TI  - A standardized surgical technique for removal of the Interstim tined lead.
AB  - INTRODUCTION: Explantation of the Interstim sacral neuromodulation (SNM) device
      is occasionally necessary. Removing the tined lead can put strain on the lead,
      resulting in a possible break and retained fragments. The Food and Drug
      Administration (FDA) released a notification regarding health consequences
      related to retained lead fragments. We describe a novel and safe surgical
      technique for removing the Interstim device and permanent lead. MATERIALS AND
      METHODS: We searched the Manufacturer and User Facility Device Experience (MAUDE)
      database for complications related to tined lead removal and searched the
      database of a single surgeon at our institution. Our standardized technique for
      tined lead removal is as follows. An incision is made over the previous lead
      insertion site and the lead is isolated and externalized. The fibrous
      encapsulation is dissected off the lead to expose the tines and ensure the lead
      is free from adhesions. The lead is removed by wrapping it around a curved
      hemostat and turning it under tension. If the lead breaks, the incision is
      extended and dissection is carried down to the sacral body to remove all
      fragments. RESULTS: Twenty-eight patients had their tined lead removed between
      2009 and 2015 after being in place a median of 2.00 years (IQR 1.32-3.32 years).
      One lead broke (3.6%) during removal over the 6 years using our standardized
      approach. CONCLUSION: Permanent tined leads can break on removal and retained
      fragments can pose significant health consequences. Our technique standardizes
      the approach for removal and is safe and effective in our series.

PMID- 27705734
TI  - Wire in the hole: a case series of eroded intrapubic wire sutures causing
      genitourinary complications in the bladder exstrophy complex.
AB  - Bladder exstrophy and cloacal exstrophy are rare congenital defects of the
      genitourinary tract that require complex surgical reconstruction. Malrotation of
      the bony pelvis causes a characteristic diastasis of the pubic symphysis, which
      is surgically reduced at the time of initial bladder closure. For a successful
      primary closure without tension such that the bladder can be placed deep within
      the pelvis, pelvic osteotomy is often used. However, alternative techniques have
      been utilized to bring the pubic rami into apposition. The authors present four
      bladder/cloacal exstrophy patients in which an intrapubic wire was used for pubic
      apposition, resulting in significant genitourinary complications.

PMID- 27705740
TI  - To cut or not to cut... that remains the question.

PMID- 27705737
TI  - Early pregnancy likely caused by an intravesical intrauterine device.
AB  - A 42-year-old female with remote history of intrauterine device (IUD) placement
      presented with gross hematuria, urinary urgency, and dyspareunia. Cystoscopy
      showed an encrusted, free-floating intravesical foreign body consistent with a
      heavily calcified IUD. It was removed endoscopically using holmium laser
      cystolitholapaxy. The patient remained symptom free postoperatively. While most
      intravesical IUDs are thought to be the result of migration after several months,
      this patient became pregnant within 4 weeks after initial insertion. Therefore
      this may represent a case either of early intravesical migration or of accidental
      IUD placement into the bladder at the time of initial insertion.

PMID- 27705736
TI  - MLL translocation in two castration-resistant prostate cancer patients.
AB  - The mixed-lineage leukemia (MLL) protein acts as a histone methyltransferase
      regulating multiple genetic elements. Rearrangements of the MLL gene result in
      expression of MLL-fusion proteins that occur in some acute leukemias and are
      associated with poor prognosis. The MLL protein complex has been shown to
      interact with the androgen receptor via the MLL-menin subunit, thus promoting
      gene activation. The presence of MLL translocation has not been previously
      reported in patients with castrate resistant prostate cancer (CRPC). We describe
      two cases of metastatic CRPC with a translocation in the MLL gene detected by a
      specific fluorescent in situ hybridization (FISH) assay. Both patients had an
      aggressive course and succumbed to the illness.

PMID- 27705735
TI  - Pyelocystostomy for treatment of recurrent nephrolithiasis and ureteropelvic
      junction obstruction in a pelvic kidney.
AB  - Patients with pelvic kidneys are at an increased risk of developing ureteropelvic
      junction obstruction (UPJO) and nephrolithiasis with limited endourologic
      options. A 54-year-old man with a left pelvic kidney, recurrent nephrolithiasis,
      and 12 previous ureteroscopies presented with left UPJO and lower pole calyceal
      stones. After two failed ureteroscopic attempts, an open pyelolithotomy and
      pyelocystostomy were performed. After 30 months, he continues to be asymptomatic
      without recurrence of nephrolithiasis. This constitutes the fifth such reported
      case. Therefore, pyelocystotomy is a good option for patients with pelvic
      kidneys, UPJO and recurrent nephrolithiasis refractory to endourologic
      procedures.

PMID- 27705738
TI  - How I do it: Same day discharge for transurethral resection of prostate using
      Olympus PlasmaButton and PlasmaLoop.
AB  - Benign prostatic hyperplasia (BPH) is one of the most common conditions affecting
      older men. Transurethral resection of the prostate (TURP) has widely been
      considered the gold standard in surgical treatment for BPH. However, this
      procedure remains largely an inpatient procedure. Inpatient admission ultimately
      adds to healthcare cost and patient morbidity. In this article, we present an
      alternative methodology to treat BPH using combination Olympus PlasmaButton and
      Olympus PlasmaLoop therapy. Preliminary results from our experience suggest
      improved hemostasis with adequate resection, allowing a majority of our patients
      to be discharged the same day of the procedure. We describe our novel technique
      as a safe and effective way to possibly treat BPH in an outpatient setting.

PMID- 27705739
TI  - Canadian Pediatrics Society position statement on newborn circumcision: a risk
      benefit analysis revisited.
AB  - INTRODUCTION: The Canadian Pediatrics Society (CPS) recently released a position
      statement on early infant (newborn) male circumcision (EIMC). It concluded that
      since benefits do not exceed risks, circumcision should only be performed on boys
      in high-risk populations or circumstances. This contradicts recommendations by
      the American Academy of Pediatrics and the Centers for Disease Control and
      Prevention (CDC) whose policies each support more widespread implementation of
      EIMC. Here we review the CPS statement, particularly its risk-benefit analysis,
      to determine the basis for this disparity. MATERIALS AND METHODS: We performed a
      risk-benefit analysis based on relevant literature retrieved from PubMed
      reporting frequency of each condition, giving emphasis to data from meta-analyses
      and randomized controlled trials. RESULTS: Although the CPS recognized some of
      the benefits of EIMC, its inclusion of weak studies of adverse events led to
      these being over-estimated, greatly exceeding the figure of < 0.5% found in a
      recent large, technically robust, CDC study. The CPS under-estimated benefits by
      omitting balanitis, balanoposthitis, prostate cancer, some sexually transmitted
      infections and candidiasis, and failing to consider lifetime prevalence of
      urinary tract infections in uncircumcised males. In contrast, our more inclusive
      risk-benefit analysis found benefits exceed risks by approximately 100 to 1 and
      that lack of EIMC contributes to adverse medical conditions, some potentially
      fatal, in approximately half of uncircumcised males. CONCLUSIONS: The 2015 CPS
      position statement on EIMC is at odds with the evidence. The CPS conclusions stem
      from errors in its risk-benefit analysis. In light of our findings we recommend
      the CPS issue a revised statement.

PMID- 27705741
TI  - Abstracts of the Mid-Atlantic Section of the American Urological Association
      Annual Meeting. October 6 - 9, 2016 Hot Springs, VA.

PMID- 27705742
TI  - Autocorrelation structure at rest predicts value correlates of single neurons
      during reward-guided choice.
AB  - Correlates of value are routinely observed in the prefrontal cortex (PFC) during
      reward-guided decision making. In previous work (Hunt et al., 2015), we argued
      that PFC correlates of chosen value are a consequence of varying rates of a
      dynamical evidence accumulation process. Yet within PFC, there is substantial
      variability in chosen value correlates across individual neurons. Here we show
      that this variability is explained by neurons having different temporal receptive
      fields of integration, indexed by examining neuronal spike rate autocorrelation
      structure whilst at rest. We find that neurons with protracted resting temporal
      receptive fields exhibit stronger chosen value correlates during choice. Within
      orbitofrontal cortex, these neurons also sustain coding of chosen value from
      choice through the delivery of reward, providing a potential neural mechanism for
      maintaining predictions and updating stored values during learning. These
      findings reveal that within PFC, variability in temporal specialisation across
      neurons predicts involvement in specific decision-making computations.

PMID- 27705743
TI  - C. elegans GLP-1/Notch activates transcription in a probability gradient across
      the germline stem cell pool.
AB  - C. elegans Notch signaling maintains a pool of germline stem cells within their
      single-celled mesenchymal niche. Here we investigate the Notch transcriptional
      response in germline stem cells using single-molecule fluorescence in situ
      hybridization coupled with automated, high-throughput quantitation. This approach
      allows us to distinguish Notch-dependent nascent transcripts in the nucleus from
      mature mRNAs in the cytoplasm. We find that Notch-dependent active transcription
      sites occur in a probabilistic fashion and, unexpectedly, do so in a steep
      gradient across the stem cell pool. Yet these graded nuclear sites create a
      nearly uniform field of mRNAs that extends beyond the region of transcriptional
      activation. Therefore, active transcription sites provide a precise view of where
      the Notch-dependent transcriptional complex is productively engaged. Our findings
      offer a new window into the Notch transcriptional response and demonstrate the
      importance of assaying nascent transcripts at active transcription sites as a
      readout for canonical signaling.

PMID- 27705748
TI  - Cornus mas L. (cornelian cherry), an important European and Asian traditional
      food and medicine: Ethnomedicine, phytochemistry and pharmacology for its
      commercial utilization in drug industry.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cornus mas L. (cornelian cherry) fruits have been
      used for centuries as traditional cuisine and folk medicine in various countries
      of Europe and Asia. In folk medicines, the fruits and other parts of the plant
      have been used for prevention and treatment of a wide range of diseases such as
      diabetes, diarrhea, gastrointestinal disorders, fevers, rheumatic pain, skin and
      urinary tract infections, kidney and liver diseases, sunstroke, among others.
      This review provides a systematic and constructive overview of ethnomedicinal
      uses, chemical constituents and pharmacological activities of this plant as well
      as future research need for its commercial utilization as nutraceutical food
      supplement and medicine. MATERIALS AND METHODS: This review is based on available
      literature on ethnomedicinal uses, phytochemical, pharmacological, toxicity and
      clinical studies on Cornus mas L. (cornelian cherry) fruits and other organs that
      was collected from electronic (SciFinder, PubMed, Science Direct and ACS among
      others) and library searches of books and journals. RESULTS: Versatile
      ethnomedicinal uses of the plant in different European and Asian countries have
      been reported. Phytochemical investigations on different parts of this plant have
      resulted in the identification of 101 compounds, among which anthocyanins,
      flavonoids and iridoids are the predominant groups. The crude extracts of fruits
      and other parts of the plant and their pure isolates exhibit a broad spectrum of
      pharmacological activities such as anti-microbial, anti-diabetic, anti
      atherosclerotic, cyto-, hepato-, neuro- and renalprotective, antiplatelet and
      antiglaucomic activities. Anthocyanins, flavonoids, iridoids and vitamin C are
      the major bioactive constituents of the fruits. Fruits are non-toxic and safe
      food on acute toxicity studies in rat and human models. Clinical trials in
      diabetic type2 and hyperlipidemic patients showed significant trends of
      amelioration in sugar level, insulin secretion in diabetic patients and
      amelioration of lipid profile, apolipoprotein status and vascular inflammation in
      hyperlipidemic patients. CONCLUSION: Based on our review, Cornus mas L.
      (cornelian cherry) fruits and leaves can be used mainly in the treatment of
      diabetes, obesity, atherosclerosis, skin diseases, gastrointestinal and rheumatic
      problems. Some indications from ethnomedicines have been validated by
      pharmacological activities of the fruits and its extracts/pure isolates. The
      reported data reveal that the fruits are a potential source for treatment of
      diabetes, obesity, hyperlipidemia and gastrointestinal disorders. Unfortunately,
      the pharmacological studies in these areas are still insufficient to substantiate
      these preventive effects in confirmatory trials on the mass-scale clinical
      settings. Future studies on mechanisms of action, bioavailability,
      pharmacokinetics and adverse effects of the extracts and their bioactive
      constituents as well as their effective doses and long term toxic effects in
      humans are needed for commercial applications of these extracts/isolates in
      modern medicines. The available literature showed that most of the activities of
      the extracts are due to their constituents, anthocyanins, flavonoids and other
      phenolics, iridoids and vitamins for their antioxidant and other properties.

PMID- 27705747
TI  - Vascular action of bisphosphonates: In vitro effect of alendronate on the
      regulation of cellular events involved in vessel pathogenesis.
AB  - In this work we investigate whether, despite the procalcific action of
      alendronate on bone, the drug would be able to regulate in vitro the main
      cellular events that take part in atherosclerotic lesion generation. Using
      endothelial cell cultures we showed that Alendronate (1-50MUM) acutely enhances
      nitric oxide production (10-30min). This stimulatory action of the bisphosphonate
      involves the participation of MAPK signaling transduction pathway. Under
      inflammatory stress, the drug reduces monocytes and platelets interactions with
      endothelial cells induced by lipopolysaccharide. Indeed the bisphophonate
      exhibits a significant inhibition of endothelial dependent platelet aggregation.
      The molecular mechanism of alendronate (ALN) on leukocyte adhesion depends on the
      regulation of the expression of cell adhesion related genes (VCAM-1; ICAM-1);
      meanwhile the antiplatelet activity is associated with the effect of the drug on
      nitric oxide production. On vascular smooth muscle cells, the drug exhibits
      ability to decrease osteogenic transdifferentiation and extracellular matrix
      mineralization. When vascular smooth muscle cells were cultured in osteogenic
      medium for 21days, they exhibited an upregulation of calcification markers (RUNX2
      and TNAP), high alkaline phosphatase activity and a great amount of
      mineralization nodules. ALN treatment significantly down-regulates mRNA levels of
      osteoblasts markers; diminishes alkaline phosphatase activity and reduces the
      extracellular calcium deposition. The effect of ALN on vascular cells differs
      from its own bone action. On calvarial osteoblasts ALN induces cell
      proliferation, enhances alkaline phosphatase activity, and increases
      mineralization, but does not affect nitric oxide synthesis. Our results support
      the hypothesis that ALN is an active drug at vascular level that regulates key
      processes involved in vascular pathogenesis through a direct action on vessel
      cells.

PMID- 27705749
TI  - High GDF-15 Serum Levels Independently Correlate with Poorer Overall Survival of
      Patients with Tumor-Free Stage III and Unresectable Stage IV Melanoma.
AB  - Biomarkers are strongly needed for diagnostic surveillance of patients with
      metastatic melanoma. On the basis of its known association with tumor metastasis
      and its ability to induce cancer cachexia, we investigated serum levels of growth
      and differentiation factor 15 (sGDF-15) as a marker for overall survival (OS).
      sGDF-15 was retrospectively measured by ELISA in 761 samples obtained at distinct
      time points during routine clinical care of patients with stage III/IV melanoma.
      In the entire cohort, sGDF-15 >= 1.5 ng/ml was strongly associated with reduced
      OS after assessment. Subsequent analyses were performed separately for tumor-free
      stage III, tumor-free stage IV, and unresectable stage IV patients. For patients
      with unresectable distant metastasis (n = 206), sGDF-15 was independently
      associated with OS when considered together with the M-category and superior to
      serum level of lactate dehydrogenase. Analysis in tumor-free stage III patients
      during routine surveillance (n = 468) revealed sGDF-15 to be associated with OS
      and an independent factor when considered together with S100B and the pattern of
      locoregional metastasis. Only in tumor-free stage IV patients (n = 87) sGDF-15
      was not associated with OS. sGDF-15 should thus be further validated as a marker
      for early detection of recurrence in stage III patients and as a prognostic or
      predictive marker particularly in the context newly available treatments in
      unresectable stage IV patients.

PMID- 27705750
TI  - A physiological characterization of the Cafeteria diet model of metabolic
      syndrome in the rat.
AB  - Many promising findings from pre-clinical research have failed to translate to
      the clinic due to their inability to incorporate human disease co-morbidity. A
      variety of rodent diets and feeding durations are currently used in models of
      human metabolic syndrome, obesity and diabetes. One model, the Cafeteria (CAF)
      diet, makes use of grocery store-purchased food items that more closely
      approximate the human ultra-processed diet than commercial high-fat or high-sugar
      rodent diets. The present study describes the development of metabolic syndrome
      in rats fed a CAF diet as well as the recovery of metabolic syndrome following a
      healthy "lifestyle" change. In addition, we explored the effects of CAF diet on
      spatial learning and memory and on neuroinflammation. Three-week old male Sprague
      Dawley rats were fed a CAF diet for three months that consisted of 16 highly
      palatable human food items along with standard chow and a 12% sucrose solution to
      mimic soda consumption. Thereafter, a sub-group of CAF diet rats was switched to
      a chow diet (SWT) for one month. Both CAF and SWT groups were compared to control
      rats maintained on a standard chow diet (SD). Prior to the diet switch, CAF and
      SWT animals developed features akin to metabolic syndrome. Both groups of rats
      displayed significant abdominal obesity with increased visceral adiposity,
      hyperinsulinemia, glucose intolerance and dyslipidemia with elevated serum
      triglyceride levels and reduced HDL cholesterol. Switching to a chow diet for one
      month completely reversed these features in SWT animals. Although acquisition of
      the Barnes maze was not affected by the CAF diet, these animals exhibited greater
      hippocampal neuroinflammation compared to both SD and SWT rats as assessed by
      Iba1 staining. These results demonstrate that the CAF diet is very effective in
      creating metabolic syndrome with hippocampal inflammation in rats over a
      relatively short time span. This model may be of great heuristic importance in
      determining potential reversibility of metabolic and cerebrovascular pathologies
      across the lifespan and as a co-morbid factor in other disease models such as
      stroke.

PMID- 27705745
TI  - RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb
      repressive complexes.
AB  - Polycomb group (PcG) proteins function as chromatin-based transcriptional
      repressors that are essential for normal gene regulation during development.
      However, how these systems function to achieve transcriptional regulation remains
      very poorly understood. Here, we discover that the histone H2AK119 E3 ubiquitin
      ligase activity of Polycomb repressive complex 1 (PRC1) is defined by the
      composition of its catalytic subunits and is highly regulated by RYBP/YAF2
      dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role
      in shaping H2AK119 mono-ubiquitylation at PcG targets and underpins an activity
      based communication between PRC1 and Polycomb repressive complex 2 (PRC2) which
      is required for normal histone H3 lysine 27 trimethylation (H3K27me3). Without
      normal histone modification-dependent communication between PRC1 and PRC2,
      repressive Polycomb chromatin domains can erode, rendering target genes
      susceptible to inappropriate gene expression signals. This suggests that activity
      based communication and histone modification-dependent thresholds create a
      localized form of epigenetic memory required for normal PcG chromatin domain
      function in gene regulation.

PMID- 27705746
TI  - A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance
      choices in C. elegans.
AB  - Ligand receptor interactions instruct axon guidance during development. How
      dendrites are guided to specific targets is less understood. The C. elegans PVD
      sensory neuron innervates muscle-skin interface with its elaborate dendritic
      branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived
      chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle
      innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the
      growth of terminal branches. Ectopic expression of LECT-2 from seam cells is
      sufficient to redirect the PVD dendrites onto seam cells. LECT-2 functions in a
      multi-protein receptor-ligand complex that also contains two transmembrane
      ligands on the skin, SAX-7/L1CAM and MNR-1, and the neuronal transmembrane
      receptor DMA-1. LECT-2 greatly enhances the binding between SAX-7, MNR-1 and DMA
      1. The activation of DMA-1 strictly requires all three ligands, which establishes
      a combinatorial code to precisely target and pattern dendritic arbors.

PMID- 27705744
TI  - Cholesterol activates the G-protein coupled receptor Smoothened to promote
      Hedgehog signaling.
AB  - Cholesterol is necessary for the function of many G-protein coupled receptors
      (GPCRs). We find that cholesterol is not just necessary but also sufficient to
      activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell
      communication system in development. Cholesterol influences Hh signaling by
      directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal
      across the membrane in all animals. Unlike many GPCRs, which are regulated by
      cholesterol through their heptahelical transmembrane domains, SMO is activated by
      cholesterol through its extracellular cysteine-rich domain (CRD). Residues shown
      to mediate cholesterol binding to the CRD in a recent structural analysis also
      dictate SMO activation, both in response to cholesterol and to native Hh ligands.
      Our results show that cholesterol can initiate signaling from the cell surface by
      engaging the extracellular domain of a GPCR and suggest that SMO activity may be
      regulated by local changes in cholesterol abundance or accessibility.

PMID- 27705751
TI  - Before and after - Nutritional transformation of dysmorphism in a case of
      Costello syndrome.
AB  - Costello syndrome is a type of RASopathy mapped to HRAS gene in chromosome 11,
      characterized by prenatal overgrowth, postnatal failure to thrive, classic facial
      gestalt and multisystem involvement including cardiomyopathy and intellectual
      disability. We present a 7 months old child with severe failure to thrive whose
      "subtle" facial dysmorphism at the time eluded clinical recognition of the
      syndrome. It was only with optimization of his nutritional status that dysmorphic
      features became more apparent, which affirmed the molecular diagnosis of Costello
      syndrome from exome sequencing. The case illustrated how drastic failure to
      thrive can be in Costello syndrome, and how nutritional status can transform
      dysmorphic features in a child. It also highlights the importance of serial
      dysmorphic evaluation in difficult cases.

PMID- 27705753
TI  - Leptin levels, seasonality and thermal acclimation in the Microbiotherid
      marsupial Dromiciops gliroides: Does photoperiod play a role?
AB  - Mammals of the Neotropics are characterized by a marked annual cycle of activity,
      which is accompanied by several physiological changes at the levels of the whole
      organism, organs and tissues. The physiological characterization of these cycles
      is important, as it gives insight on the mechanisms by which animals adjust
      adaptively to seasonality. Here we studied the seasonal changes in blood
      biochemical parameters in the relict South American marsupial Dromiciops
      gliroides ("monito del monte" or "little mountain monkey"), under semi-natural
      conditions. We manipulated thermal conditions in order to characterize the
      effects of temperature and season on a battery of biochemical parameters, body
      mass and adiposity. Our results indicate that monitos experience an annual cycle
      in body mass and adiposity (measured as leptin levels), reaching a maximum in
      winter and a minimum in summer. Blood biochemistry confirms that the nutritional
      condition of animals is reduced in summer instead of winter (as generally
      reported). This was coincident with a reduction of several biochemical parameters
      in summer, such as betahydroxybutyrate, cholesterol, total protein concentration
      and globulins. Monitos seem to initiate winter preparation during autumn and
      reach maximum body reserves in winter. Hibernation lasts until spring, at which
      time they use fat reserves and become reproductively active. Sexual maturation
      during summer would be the strongest energetic bottleneck, which explains the
      reductions in body mass and other parameters in this season. Overall, this study
      suggests that monitos anticipate the cold season by a complex interaction of
      photoperiodic and thermal cues.

PMID- 27705757
TI  - Twist and Probe-Fluorescent Molecular Rotors Image Escherichia coli Cell Membrane
      Viscosity.

PMID- 27705755
TI  - Lindenane sesquiterpenoid dimers from Chloranthus japonicus inhibit HIV-1 and HCV
      replication.
AB  - Phytochemical investigation on the whole plant of Chloranthus japonicus
      (Chloranthaceae) led to the isolation and identification of three new lindenane
      type sesquiterpenoid dimers, chlorajaponilides F-H (1-3), along with seven known
      ones (4-10). Their chemical structures were established by extensive spectral
      evidence. Compounds 1 and 2 are both dimeric sesquiterpenoids featuring a rare
      hydroperoxy group at C-5. All compounds were tested for their activities on wild
      type HIV-1 replication and compounds 1, 2, 5, and 9 were effective with EC50
      values from 3.08 to 17.16MUM. All these four compounds showed the same inhibitory
      effects on the two NNRTI-resistant HIV strains as on wild-type HIV-1 with EC50
      change folds from 0.61 to 1.6MUM. Furthermore, compounds 1, 5, and 9 exhibited
      inhibitory activities on HCV replication with the similar potency as their
      activities on HIV-1. Our finding may provide a clue to address the problem of HIV
      1 and HCV co-infection.

PMID- 27705756
TI  - Epicardial fat is associated with severity of subclinical coronary
      atherosclerosis in familial hypercholesterolemia.
AB  - BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common genetic
      disorder characterized by elevated blood cholesterol, increased prevalence of
      subclinical atherosclerosis and high risk of premature coronary heart disease.
      However, this risk is not explained solely by elevated LDL-cholesterol
      concentrations, and other factors may influence atherosclerosis development.
      There is evidence that increased adiposity may predispose to atherosclerosis in
      FH. Epicardial fat has been associated with subclinical coronary atherosclerosis
      in the general population. This study evaluated the association of epicardial fat
      (EFV) volume with the presence and extent of subclinical coronary atherosclerosis
      detected by computed tomography angiography in FH patients. METHODS: Ninety-seven
      FH subjects (35% male, mean age 45 +/- 13 years, LDL-C 281 +/- 56 mg/dL, 67% with
      proven molecular defects) underwent computed tomography angiography and coronary
      artery calcium (CAC) scoring. EFV was measured in non-contrast images using a
      semi-automated method. Segment-stenosis score (SSS) and segment-involvement score
      (SIS) were calculated. Multivariate Poisson regression was utilized to assess an
      independent association of EFV with coronary atherosclerotic burden. RESULTS: EFV
      was positively associated with age, body mass index, waist circumference, blood
      glucose, the presence of the metabolic syndrome components, but not with LDL-C.
      After adjusting for confounders and abdominal circumference, an independent
      association (shown as beta coefficients and 95% confidence intervals) of EVF with
      CAC scores [beta = 0.263 (0.234; 0.292), p=0.000], SIS [beta = 0.304 (0.141;
      0.465) p=0.000] and SSS [beta = 0.296 (0.121; 0.471), p=0.001] was found.
      CONCLUSIONS: In FH, EFV was independently associated with coronary
      atherosclerotic presence and severity.

PMID- 27705754
TI  - The effect of l-thymidine, acyclic thymine and 8-bromoguanine on the stability of
      model G-quadruplex structures.
AB  - BACKGROUND: Guanine-rich oligonucleotides are capable of forming tetrahelical
      structures known as G-quadruplexes with interesting biological properties. We
      have investigated the effects of site-specific substitution in the loops and in
      the tetrads model G-quadruplexes using thymine glycol nucleic acid (GNA) units, l
      thymidine and 8-Br-2'-deoxyguanosine. METHODS: Modified oligonucleotides were
      chemically synthesized and spectroscopic techniques were used to determine the
      relative stability of the modified G-quadruplex. The double 8-BrdG-modified
      quadruplexes were further characterized by Nuclear Magnetic Resonance. Binding to
      thrombin of selected quadruplex was analyzed by gel electrophoresis retention
      assay. RESULTS: The most interesting results were found with a 8-bromoG
      substitution that had the larger stabilization of the quadruplex. NMR studies
      indicate a tight relationship between the loops and the tetrads to accommodate 8
      bromoG modifications within the TBA. CONCLUSIONS: The substitutions of loop
      positions with GNA T affect the TBA stability except for single modification in
      T7 position. Single l-thymidine substitutions produced destabilization of TBA.
      Larger changes on quadruplex stability are observed with the use of 8-bromoG
      finding a single substitution with the highest thermal stabilization found in
      thrombin binding aptamers modified at the guanine residues and having good
      affinity for thrombin. Double 8-BrdG modification in anti positions of different
      tetrads produce a conformational flip from syn to anti conformation of 8-Br-dG to
      favor loop-tetrad interaction and preserve the overall TBA stability. GENERAL
      SIGNIFICANCE: Modified guanine-rich oligonucleotides are valuable tools for the
      search for G-quadruplex structures with higher thermal stability and may provide
      compounds with interesting protein-nucleic acid binding properties. This article
      is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta
      Giancola and Dr. Daniela Montesarchio.

PMID- 27705758
TI  - Large-Scale Conformational Transitions in Supercoiled DNA Revealed by Coarse
      Grained Simulation.
AB  - Topological constraints, such as those associated with DNA supercoiling, play an
      integral role in genomic regulation and organization in living systems. However,
      physical understanding of the principles that underlie DNA organization at
      biologically relevant length scales remains a formidable challenge. We develop a
      coarse-grained simulation approach for predicting equilibrium conformations of
      supercoiled DNA. Our methodology enables the study of supercoiled DNA molecules
      at greater length scales and supercoiling densities than previously explored by
      simulation. With this approach, we study the conformational transitions that
      arise due to supercoiling across the full range of supercoiling densities that
      are commonly explored by living systems. Simulations of ring DNA molecules with
      lengths at the scale of topological domains in the Escherichia coli chromosome
      (~10 kilobases) reveal large-scale conformational transitions elicited by
      supercoiling. The conformational transitions result in three supercoiling
      conformational regimes that are governed by a competition among chiral coils,
      extended plectonemes, and branched hyper-supercoils. These results capture the
      nonmonotonic relationship of size versus degree of supercoiling observed in
      experimental sedimentation studies of supercoiled DNA, and our results provide a
      physical explanation of the conformational transitions underlying this behavior.
      The length scales and supercoiling regimes investigated here coincide with those
      relevant to transcription-coupled remodeling of supercoiled topological domains,
      and we discuss possible implications of these findings in terms of the interplay
      between transcription and topology in bacterial chromosome organization.

PMID- 27705759
TI  - Thermal Stability of RNA Structures with Bulky Cations in Mixed Aqueous
      Solutions.
AB  - Bulky cations are used to develop nucleic-acid-based technologies for medical and
      technological applications in which nucleic acids function under nonaqueous
      conditions. In this study, the thermal stability of RNA structures was measured
      in the presence of various bulky cations in aqueous mixtures with organic
      solvents or polymer additives. The stability of oligonucleotide, transfer RNA,
      and polynucleotide structures was decreased in the presence of salts of
      tetrabutylammonium and tetrapentylammonium ions, and the stability and salt
      concentration dependences were dependent on cation sizes. The degree to which
      stability was dependent on salt concentration was correlated with reciprocals of
      the dielectric constants of mixed solutions, regardless of interactions between
      the cosolutes and RNA. Our results show that organic solvents affect the strength
      of electrostatic interactions between RNA and cations. Analysis of ion binding to
      RNA indicated greater enhancement of cation binding to RNA single strands than to
      duplexes in media with low dielectric constants. Furthermore, background bulky
      ions changed the dependence of RNA duplex stability on the concentration of metal
      ion salts. These unique properties of large tetraalkylammonium ions are useful
      for controlling the stability of RNA structures and its sensitivity to metal ion
      salts.

PMID- 27705752
TI  - SOX2, OCT3/4 and NANOG expression and cellular plasticity in rare human somatic
      cells requires CD73.
AB  - Endogenous Plastic Somatic (ePS) cells isolated from adult human tissues exhibit
      extensive lineage plasticity in vitro and in vivo. Here we visualize these rare
      ePS cells in a latent state, i.e. lacking SOX2, OCT3/4 and NANOG (SON)
      expression, in non-diseased breast specimens through immunohistochemical analysis
      of previously identified ePS-specific biomarkers (CD73+, EpCAM+ and CD90-). We
      also report a novel mechanism by which these latent ePS cells acquire SON
      expression and plasticity in vitro. Four extracellular factors are necessary for
      the acquisition of SON expression and lineage plasticity in ePS cells: adenosine
      (which is produced by the 5' ecto-nucleotidase CD73 and activates in turn the PKA
      dependent IL6/STAT3 pathway through the adenosine receptor ADORA2b), IL6, FGF2
      and ACTIVIN A. Blocking any pathway component renders ePS cells incapable of SON
      expression and lineage plasticity. Notably, hESCs do not use adenosine or IL6 nor
      they express CD73 or ADORA2b and inhibition of adenosine signaling does not
      ablate their plasticity. Therefore, the data presented here delineate novel
      circuitry and physiological signals for accessing SON expression in rare,
      undifferentiated human cells.

PMID- 27705761
TI  - Single-Molecule Analysis beyond Dwell Times: Demonstration and Assessment in and
      out of Equilibrium.
AB  - We present a simple and robust technique for extracting kinetic rate models and
      thermodynamic quantities from single-molecule time traces. Single-molecule
      analysis of complex kinetic sequences (SMACKS) is a maximum-likelihood approach
      that resolves all statistically relevant rates and also their uncertainties. This
      is achieved by optimizing one global kinetic model based on the complete data set
      while allowing for experimental variations between individual trajectories. In
      contrast to dwell-time analysis, which is the current standard method, SMACKS
      includes every experimental data point, not only dwell times. As a result, it
      works as well for long trajectories as for an equivalent set of short ones. In
      addition, the previous systematic overestimation of fast over slow rates is
      solved. We demonstrate the power of SMACKS on the kinetics of the multidomain
      protein Hsp90 measured by single-molecule Forster resonance energy transfer.
      Experiments in and out of equilibrium are analyzed and compared to simulations,
      shedding new light on the role of Hsp90's ATPase function. SMACKS resolves
      accurate rate models even if states cause indistinguishable signals. Thereby, it
      pushes the boundaries of single-molecule kinetics beyond those of current
      methods.

PMID- 27705760
TI  - Imaging the Nonlinear Susceptibility Tensor of Collagen by Nonlinear Optical
      Stokes Ellipsometry.
AB  - Nonlinear optical Stokes ellipsometric (NOSE) microscopy was demonstrated for the
      analysis of collagen-rich biological tissues. NOSE is based on polarization
      dependent second harmonic generation imaging. NOSE was used to access the
      molecular-level distribution of collagen fibril orientation relative to the local
      fiber axis at every position within the field of view. Fibril tilt-angle
      distribution was investigated by combining the NOSE measurements with ab initio
      calculations of the predicted molecular nonlinear optical response of a single
      collagen triple helix. The results were compared with results obtained previously
      by scanning electron microscopy, nuclear magnetic resonance imaging, and electron
      tomography. These results were enabled by first measuring the laboratory-frame
      Jones nonlinear susceptibility tensor, then extending to the local-frame tensor
      through pixel-by-pixel corrections based on local orientation.

PMID- 27705762
TI  - Urea-Dependent Adenylate Kinase Activation following Redistribution of Structural
      States.
AB  - Proteins are often functionally dependent on conformational changes that allow
      them to sample structural states that are sparsely populated in the absence of a
      substrate or binding partner. The distribution of such structural microstates is
      governed by their relative stability, and the kinetics of their interconversion
      is governed by the magnitude of associated activation barriers. Here, we have
      explored the interplay among structure, stability, and function of a selected
      enzyme, adenylate kinase (Adk), by monitoring changes in its enzymatic activity
      in response to additions of urea. For this purpose we used a 31P NMR assay that
      was found useful for heterogeneous sample compositions such as presence of urea.
      It was found that Adk is activated at low urea concentrations whereas higher urea
      concentrations unfolds and thereby deactivates the enzyme. From a quantitative
      analysis of chemical shifts, it was found that urea redistributes preexisting
      structural microstates, stabilizing a substrate-bound open state at the expense
      of a substrate-bound closed state. Adk is rate-limited by slow opening of
      substrate binding domains and the urea-dependent redistribution of structural
      states is consistent with a model where the increased activity results from an
      increased rate-constant for domain opening. In addition, we also detected a
      strong correlation between the catalytic free energy and free energy of substrate
      (ATP) binding, which is also consistent with the catalytic model for Adk. From a
      general perspective, it appears that urea can be used to modulate conformational
      equilibria of folded proteins toward more expanded states for cases where a
      sizeable difference in solvent-accessible surface area exists between the states
      involved. This effect complements the action of osmolytes, such as trimethylamine
      N-oxide, that favor more compact protein states.

PMID- 27705763
TI  - A Novel Voltage Sensor in the Orthosteric Binding Site of the M2 Muscarinic
      Receptor.
AB  - G protein-coupled receptors (GPCRs) mediate many signal transduction processes in
      the body. The discovery that these receptors are voltage-sensitive has changed
      our understanding of their behavior. The M2 muscarinic acetylcholine receptor
      (M2R) was found to exhibit depolarization-induced charge movement-associated
      currents, implying that this prototypical GPCR possesses a voltage sensor.
      However, the typical domain that serves as a voltage sensor in voltage-gated
      channels is not present in GPCRs, making the search for the voltage sensor in the
      latter challenging. Here, we examine the M2R and describe a voltage sensor that
      is comprised of tyrosine residues. This voltage sensor is crucial for the voltage
      dependence of agonist binding to the receptor. The tyrosine-based voltage sensor
      discovered here constitutes a noncanonical by which membrane proteins may sense
      voltage.

PMID- 27705765
TI  - Semiclosed Conformations of the Ligand-Binding Domains of NMDA Receptors during
      Stationary Gating.
AB  - NMDA receptors are tetrameric ligand-gated ion channels. In the continuous
      presence of saturating agonists, NMDA receptors undergo stationary gating, in
      which the channel stochastically switches between an open state that permits ion
      conductance and a closed state that prevents permeation. The ligand-binding
      domains (LBDs) of the four subunits are expected to have closed clefts in the
      channel-open state. On the other hand, there is little knowledge about the
      conformational status of the LBDs in the channel-closed state during stationary
      gating. To probe the latter conformational status, Kussius and Popescu engineered
      interlobe disulfide cross-links in NMDA receptors and found that the cross
      linking produced stationary gating kinetics that differed only subtly from that
      produced by agonist binding. These authors assumed that the cross-linking
      immobilized the LBDs in cleft-closed conformations, and consequently concluded
      that throughout stationary gating, agonist-bound LBDs also stayed predominantly
      in cleft-closed conformations and made only infrequent excursions to cleft-open
      conformations. Here, by calculating the conformational free energies of cross
      linked and agonist-bound LBDs, we assess whether cross-linking actually traps the
      LBDs in cleft-closed conformations and delineate semiclosed conformations of
      agonist-bound LBDs that may potentially be thermodynamically and kinetically
      important during stationary gating. Our free-energy results show that the cross
      linked LBDs are not locked in the fully closed form; rather, they sample
      semiclosed conformations almost as readily as the agonist-bound LBDs. Several
      lines of reasoning suggest that LBDs are semiclosed in the channel-closed state
      during stationary gating. Our free-energy simulations suggest possible structural
      details of such semiclosed LBD conformations, including intra- and intermolecular
      interactions that serve as alternatives to those in the cleft-closed
      conformations.

PMID- 27705764
TI  - Role of the Native Outer-Membrane Environment on the Transporter BtuB.
AB  - BtuB is a TonB-dependent transporter that permits the high-affinity binding and
      transport of cobalamin (CBL), or vitamin B12, across the asymmetric outer
      membrane (OM) of Gram-negative bacteria. It has been shown that Ca2+ binding is
      necessary for high-affinity binding of CBL to BtuB, and earlier simulations
      suggested that calcium ions serve to stabilize key substrate-binding
      extracellular loops. However, those simulations did not account for the
      lipopolysaccharides in the OM. To illuminate the roles of both Ca2+ and
      lipopolysaccharides in protein functionality, we performed simulations of apo and
      Ca2+-loaded BtuB in symmetric and asymmetric bilayers. The simulations reveal
      that the oligosaccharides of LPS stabilize the extracellular loops to some
      degree, apparently obviating the need for Ca2+. However, it is shown that Ca2+
      ions stabilize a key substrate-binding loop to an even greater degree, as well as
      reposition specific CBL-binding residues, bringing them closer to the
      organization found in the CBL-bound structure. These results indicate the
      importance of including realistic membrane models when simulating outer-membrane
      proteins.

PMID- 27705766
TI  - Investigation of LRRC8-Mediated Volume-Regulated Anion Currents in Xenopus
      Oocytes.
AB  - Volume-regulated anion channels (VRACs) play an important role in controlling
      cell volume by opening upon cell swelling. Recent work has shown that heteromers
      of LRRC8A with other LRRC8 members (B, C, D, and E) form the VRAC. Here, we used
      Xenopus oocytes as a simple system to study LRRC8 proteins. We discovered that
      adding fluorescent proteins to the C-terminus resulted in constitutive anion
      channel activity. Using these constructs, we reproduced previous findings
      indicating that LRRC8 heteromers mediate anion and osmolyte flux with subunit
      dependent kinetics and selectivity. Additionally, we found that LRRC8 heteromers
      mediate glutamate and ATP flux and that the inhibitor carbenoxolone acts from the
      extracellular side, binding to probably more than one site. Our results also
      suggest that the stoichiometry of LRRC8 heteromers is variable, with a number of
      subunits >=6, and that the heteromer composition depends on the relative
      expression of different subunits. The system described here enables easy
      structure-function analysis of LRRC8 proteins.

PMID- 27705767
TI  - Binding of Vinculin to Lipid Membranes in Its Inhibited and Activated States.
AB  - Phosphoinositols are an important class of phospholipids that are involved in a
      myriad of cellular processes, from cell signaling to motility and adhesion.
      Vinculin (Vn) is a major adaptor protein that regulates focal adhesions in
      conjunction with PIP2 in lipid membranes and other cytoskeletal components. The
      binding and unbinding transitions of Vn at the membrane interface are an
      important link to understanding the coordination of cell signaling and motility.
      Using different biophysical tools, including atomic force microscopy combined
      with confocal fluorescence microscopy and Fourier transform infrared
      spectroscopy, we studied the nanoscopic interactions of activated and
      autoinhibited states of Vn with lipid membranes. We hypothesize that a weak
      interaction occurs between Vn and lipid membranes, which leads to binding of
      autoinhibited Vn to supported lipid bilayers, and to unbinding in freestanding
      lipid vesicles. Likely driving forces may include tethering of the C-terminus to
      the lipid membrane, as well as hydrophobic helix-membrane interactions.
      Conversely, activated Vn binds strongly to membranes through specific
      interactions with clusters of PIP2 embedded in lipid membranes. Activated Vn
      harbored on PIP2 clusters may form small oligomeric interaction platforms for
      further interaction partners, which is necessary for the proper function of focal
      adhesion points.

PMID- 27705768
TI  - Modulating Vesicle Adhesion by Electric Fields.
AB  - We introduce an experimental setup for modulating adhesion of giant unilamellar
      vesicles to a planar substrate. Adhesion is induced by the application of an
      external potential to a transparent indium tin oxide-coated electrode (the
      substrate), which enables single-vesicle studies. We demonstrate tunable and
      reversible adhesion of negatively charged vesicles. The adhesion energy at
      different potentials is calculated from the vesicle shape assessed with confocal
      microscopy. Two approaches for these estimates are employed: one based on the
      whole contour of the vesicle and a second based on the contact curvature of the
      membrane in the vicinity of the substrate. Both approaches agree well with each
      other and show that the adhering vesicles are in the weak adhesion regime for the
      range of explored external potentials. Using fluorescence quenching assays, we
      detect that, in the adhering membrane segment, only the outer bilayer leaflet of
      the vesicle is depleted of negatively charged fluorescent lipids, while the inner
      leaflet remains unaffected. We show that depletion of negatively charged lipids
      is consistent Poisson-Boltzmann theory, taking into account charge regulation
      from lipid mobility. Finally, we also show that lipid diffusion is not
      significantly affected in the adhering membrane segment. We believe that the
      approaches introduced here for modulating and assessing vesicle adhesion have
      many potential applications in the field of single-vesicle studies and research
      on membrane adhesion.

PMID- 27705770
TI  - A Tensegrity Model of Cell Reorientation on Cyclically Stretched Substrates.
AB  - Deciphering the mechanisms underlying the high sensitivity of cells to mechanical
      microenvironments is crucial for understanding many physiological and
      pathological processes, e.g., stem cell differentiation and cancer cell
      metastasis. Here, a cytoskeletal tensegrity model is proposed to study the
      reorientation of polarized cells on a substrate under biaxial cyclic deformation.
      The model consists of four bars, representing the longitudinal stress fibers and
      lateral actin network, and eight strings, denoting the microfilaments. It is
      found that the lateral bars in the tensegrity, which have been neglected in most
      of the existing models, can play a vital role in regulating the cellular
      orientation. The steady orientation of cells can be quantitatively determined by
      the geometric dimensions and elastic properties of the tensegrity elements, as
      well as the frequency and biaxial ratio of the cyclic stretches. It is shown that
      this tensegrity model can reproduce all available experimental observations. For
      example, the dynamics of cell reorientation is captured by an exponential scaling
      law with a characteristic time that is independent of the loading frequency at
      high frequencies and scales inversely with the square of the strain amplitude.
      This study suggests that tensegrity type models may be further developed to
      understand cellular responses to mechanical microenvironments and provide
      guidance for engineering delicate cellular mechanosensing systems.

PMID- 27705771
TI  - Direct Tracking of Particles and Quantification of Margination in Blood Flow.
AB  - Margination refers to the migration of particles toward blood vessel walls during
      blood flow. Understanding the mechanisms that lead to margination will aid in
      tailoring the attributes of drug-carrying particles for effective drug delivery.
      Most previous studies evaluated the margination propensity of these particles via
      an adhesion mechanism, i.e., by measuring the number of particles that adhered to
      the channel wall. Although particle adhesion and margination are related,
      adhesion also depends on other factors. In this study, we quantified the
      margination propensity of particles of varying diameters (0.53, 0.84, and 2.11
      MUm) and apparent wall shear rates (30, 61, and 121 s-1) by directly tracking
      fluorescent particles flowing through a microfluidic channel. The margination
      parameter, M, is defined as the total number of particles found within the cell
      free layers normalized by the total number of particles that passed through the
      channel. In this study, an M-value of 0.2 indicated no margination, which was
      observed for all particle sizes in water. In the case of blood, larger particles
      were found to have higher M-values and thus marginated more effectively than
      smaller particles. The corresponding M-values at the device outlet were 0.203,
      0.223, and 0.285 for 0.53-, 0.84-, and 2.11-MUm particles, respectively. At the
      inlet, the M-values for all particle sizes in blood were <0.2, suggesting that
      non-fully-developed flow and constriction may lead to demargination. For particle
      velocities transverse to the flow direction (vy), all particle sizes showed a
      larger standard deviation of vy as well as a higher effective diffusivity when
      the particles were suspended in blood relative to water. These higher values are
      attributed to collisions between the blood cells and particles, further
      supporting recent simulation results. In terms of flow rates, for a given
      particle size, the higher the flow rate, the higher the M-value.

PMID- 27705772
TI  - Scattering of Cell Clusters in Confinement.
AB  - Epithelial-to-mesenchymal transition (EMT) enables scattering of cell clusters
      and disseminates motile cells to distant locations in vivo during embryonic
      development and cancer metastasis. Both stiffness and topography of the
      extracellular matrix (ECM) have been shown to influence EMT. In this work, we
      examine how the integrity of epithelial cell clusters is regulated by subcellular
      forces, protrusions, and adhesions for varying ECM inputs, such as stiffness,
      topography, and dimensionality. Our model simulates multicell networks of defined
      sizes and shapes in ECMs of varied stiffness and geometry. The integrity of cell
      clusters is dictated by cell-cell junctions, which depend on subcellular forces
      and adhesion dynamics within each cell of the cluster. Our simulations
      demonstrate an enhanced dissociation of cell-cell junctions in stiffer and more
      confined three-dimensional (3D) environments, consistent with experimental
      findings. In narrow channels, the cell edges parallel to the axis of channels
      lose their cell-cell junctions more readily than those oriented in the
      perpendicular direction. The inhibition of protrusive activity and cell polarity
      disables confinement-dependent cell scattering. Here, cell adhesion and spreading
      along channel walls is found to be essential for scattering. The model also
      predicts that two-dimensional (2D) confinement of clusters restricts cell
      spreading and simultaneously blunts the confinement-sensitive cell scattering.
      This new, to our knowledge, multiscale model integrates molecular adhesion
      dynamics, subcellular forces, cellular deformation, and macroscale mechanical
      properties of the ECM to predict the state of cell clusters of defined shapes and
      sizes. The predictions made by our model not only match experimental findings
      from a number of experimental setups, but also provide a new conceptual framework
      for understanding mechanosensitive cell scattering and EMT.

PMID- 27705769
TI  - Myosin-Induced Gliding Patterns at Varied [MgATP] Unveil a Dynamic Actin
      Filament.
AB  - Actin filaments have key roles in cell motility but are generally claimed to be
      passive interaction partners in actin-myosin-based motion generation. Here, we
      present evidence against this static view based on an altered myosin-induced
      actin filament gliding pattern in an in vitro motility assay at varied [MgATP].
      The statistics that characterize the degree of meandering of the actin filament
      paths suggest that for [MgATP] >= 0.25 mM, the flexural rigidity of heavy
      meromyosin (HMM)-propelled actin filaments is similar (without phalloidin) or
      slightly lower (with phalloidin) than that of HMM-free filaments observed in
      solution without surface tethering. When [MgATP] was reduced to <=0.1 mM, the
      actin filament paths in the in vitro motility assay became appreciably more
      winding in both the presence and absence of phalloidin. This effect of lowered
      [MgATP] was qualitatively different from that seen when HMM was mixed with ATP
      insensitive, N-ethylmaleimide-treated HMM (NEM-HMM; 25-30%). In particular, the
      addition of NEM-HMM increased a non-Gaussian tail in the path curvature
      distribution as well as the number of events in which different parts of an actin
      filament followed different paths. These effects were the opposite of those
      observed with reduced [MgATP]. Theoretical modeling suggests a 30-40% lowered
      flexural rigidity of the actin filaments at [MgATP] <= 0.1 mM and local bending
      of the filament front upon each myosin head attachment. Overall, the results fit
      with appreciable structural changes in the actin filament during actomyosin-based
      motion generation, and modulation of the actin filament mechanical properties by
      the dominating chemomechanical actomyosin state.

PMID- 27705775
TI  - Measuring the Viscosity of the Escherichia coli Plasma Membrane Using Molecular
      Rotors.
AB  - The viscosity is a highly important parameter within the cell membrane, affecting
      the diffusion of small molecules and, hence, controlling the rates of
      intracellular reactions. There is significant interest in the direct,
      quantitative assessment of membrane viscosity. Here we report the use of
      fluorescence lifetime imaging microscopy of the molecular rotor BODIPY C10 in the
      membranes of live Escherichia coli bacteria to permit direct quantification of
      the viscosity. Using this approach, we investigated the viscosity in live E. coli
      cells, spheroplasts, and liposomes made from E. coli membrane extracts. For live
      cells and spheroplasts, the viscosity was measured at both room temperature (23
      degrees C) and the E. coli growth temperature (37 degrees C), while the membrane
      extract liposomes were studied over a range of measurement temperatures (5-40
      degrees C). At 37 degrees C, we recorded a membrane viscosity in live E. coli
      cells of 950 cP, which is considerably higher than that previously observed in
      other live cell membranes (e.g., eukaryotic cells, membranes of Bacillus
      vegetative cells). Interestingly, this indicates that E. coli cells exhibit a
      high degree of lipid ordering within their liquid-phase plasma membranes.

PMID- 27705777
TI  - Unified Theory for Polarization Analysis in Second Harmonic and Sum Frequency
      Microscopy.
AB  - A unified theoretical framework for the recovery of second-order nonlinear
      susceptibility tensors and sample orientations from polarization-dependent second
      harmonic generation and sum frequency generation microscopy was developed. Jones
      formalism was extended to nonlinear optics and was used to bridge the
      experimental observables and the local-frame tensor elements. Four commonly used
      experimental architectures were explicitly explored, including polarization
      rotation with no postsample optics, polarization-in polarization-out measurement,
      and polarization modulation with and without postsample optics. Polarization
      dependent second harmonic generation measurement was performed on Z-cut quartz
      and the local-frame tensor elements were calculated. The recovered tensor
      elements agree with the expected values dictated by symmetry.

PMID- 27705778
TI  - Positive Quantitative Relationship between EMT and Contact-Initiated Sliding on
      Fiber-like Tracks.
AB  - Epithelial-mesenchymal transition (EMT) is a complex process by which cells
      acquire invasive properties that enable escape from the primary tumor. Complete
      EMT, however, is not required for metastasis: circulating tumor cells exhibit
      hybrid epithelial-mesenchymal states, and genetic perturbations promoting partial
      EMT induce metastasis in vivo. An open question is whether and to what extent
      intermediate stages of EMT promote invasiveness. Here, we investigate this
      question, building on recent observation of a new invasive property. Migrating
      cancer cell lines and cells transduced with prometastatic genes slide around
      other cells on spatially confined, fiberlike micropatterns. We show here that low
      dosage/short-duration exposure to transforming growth factor beta (TGFbeta)
      induces partial EMT and enables sliding on narrower (26 MUm) micropatterns than
      untreated counterparts (41 MUm). High-dosage/long-duration exposure induces more
      complete EMT, including disrupted cell-cell contacts and reduced E-cadherin
      expression, and promotes sliding on the narrowest (15 MUm) micropatterns. These
      results identify a direct and quantitative relationship between EMT and cell
      sliding and show that EMT-associated invasive sliding is progressive, with cells
      that undergo partial EMT exhibiting intermediate sliding behavior and cells that
      transition more completely through EMT displaying maximal sliding. Our findings
      suggest a model in which fiber maturation and EMT work synergistically to promote
      invasiveness during cancer progression.

PMID- 27705774
TI  - Mechanism of Axonal Contractility in Embryonic Drosophila Motor Neurons In Vivo.
AB  - Several in vitro and limited in vivo experiments have shown that neurons maintain
      a rest tension along their axons intrinsically. They grow in response to stretch
      but contract in response to loss of tension. This contraction eventually leads to
      the restoration of the rest tension in axons. However, the mechanism by which
      axons maintain tension in vivo remains elusive. The objective of this work is to
      elucidate the key cytoskeletal components responsible for generating tension in
      axons. Toward this goal, in vivo experiments were conducted on single axons of
      embryonic Drosophila motor neurons in the presence of various drugs. Each axon
      was slackened mechanically by bringing the neuromuscular junction toward the
      central nervous system multiple times. In the absence of any drug, axons
      shortened and restored the straight configuration within 2-4 min of slackening.
      The total shortening was ~40% of the original length. The recovery rate in each
      cycle, but not the recovery magnitude, was dependent on the axon's prior
      contraction history. For example, the contraction time of a previously slackened
      axon may be twice its first-time contraction. This recovery was significantly
      hampered with the depletion of ATP, inhibition of myosin motors, and disruption
      of actin filaments. The disruption of microtubules did not affect the recovery
      magnitude, but, on the contrary, led to an enhanced recovery rate compared to
      control cases. These results suggest that the actomyosin machinery is the major
      active element in axonal contraction, whereas microtubules contribute as
      resistive/dissipative elements.

PMID- 27705779
TI  - Shape Selection of Surface-Bound Helical Filaments: Biopolymers on Curved
      Membranes.
AB  - Motivated to understand the behavior of biological filaments interacting with
      membranes of various types, we employ a theoretical model for the shape and
      thermodynamics of intrinsically helical filaments bound to curved membranes. We
      show that filament-surface interactions lead to a host of nonuniform shape
      equilibria, in which filaments progressively unwind from their native twist with
      increasing surface interaction and surface curvature, ultimately adopting uniform
      contact curved shapes. The latter effect is due to nonlinear coupling between
      elastic twist and bending of filaments on anisotropically curved surfaces such as
      the cylindrical surfaces considered here. Via a combination of numerical
      solutions and asymptotic analysis of shape equilibria, we show that filament
      conformations are critically sensitive to the surface curvature in both the
      strong- and weak-binding limits. These results suggest that local structure of
      membrane-bound chiral filaments is generically sensitive to the curvature radius
      of the surface to which it is bound, even when that radius is much larger than
      the filament's intrinsic pitch. Typical values of elastic parameters and
      interaction energies for several prokaryotic and eukaryotic filaments indicate
      that biopolymers are inherently very sensitive to the coupling between twist,
      interactions, and geometry and that this could be exploited for regulation of a
      variety of processes such as the targeted exertion of forces, signaling, and self
      assembly in response to geometric cues including the local mean and Gaussian
      curvatures.

PMID- 27705773
TI  - A Computational Model for Kinetic Studies of Cadherin Binding and Clustering.
AB  - Cadherin is a cell-surface transmembrane receptor that mediates calcium-dependent
      cell-cell adhesion and is a major component of adhesive junctions. The formation
      of intercellular adhesive junctions is initiated by trans binding between
      cadherins on adjacent cells, which is followed by the clustering of cadherins via
      the formation of cis interactions between cadherins on the same cell membranes.
      Moreover, classical cadherins have multiple glycosylation sites along their
      extracellular regions. It was found that aberrant glycosylation affects the
      adhesive function of cadherins and correlates with metastatic phenotypes of
      several cancers. However, a mechanistic understanding of cadherin clustering
      during cell adhesion and the role of glycosylation in this process is still
      lacking. Here, we designed a kinetic model that includes multistep reaction
      pathways for cadherin clustering. We further applied a diffusion-reaction
      algorithm to numerically simulate the clustering process using a recently
      developed coarse-grained model. Using experimentally measured rates of trans
      binding between soluble E-cadherin extracellular domains, we conducted
      simulations of cadherin-mediated cell-cell binding kinetics, and the results are
      quantitatively comparable to experimental data from micropipette experiments. In
      addition, we show that incorporating cadherin clustering via cis interactions
      further increases intercellular binding. Interestingly, a two-phase kinetic
      profile was derived under the assumption that glycosylation regulates the kinetic
      rates of cis interactions. This two-phase profile is qualitatively consistent
      with experimental results from micropipette measurements. Therefore, our
      computational studies provide new, to our knowledge, insights into the molecular
      mechanism of cadherin-based cell adhesion.

PMID- 27705780
TI  - Anisotropic Membrane Curvature Sensing by Amphipathic Peptides.

PMID- 27705776
TI  - A Chemomechanical Model for Nuclear Morphology and Stresses during Cell
      Transendothelial Migration.
AB  - It is now evident that the cell nucleus undergoes dramatic shape changes during
      important cellular processes such as cell transmigration through extracellular
      matrix and endothelium. Recent experimental data suggest that during cell
      transmigration the deformability of the nucleus could be a limiting factor, and
      the morphological and structural alterations that the nucleus encounters can
      perturb genomic organization that in turn influences cellular behavior. Despite
      its importance, a biophysical model that connects the experimentally observed
      nuclear morphological changes to the underlying biophysical factors during
      transmigration through small constrictions is still lacking. Here, we developed a
      universal chemomechanical model that describes nuclear strains and shapes and
      predicts thresholds for the rupture of the nuclear envelope and for nuclear
      plastic deformation during transmigration through small constrictions. The model
      includes actin contraction and cytosolic back pressure that squeeze the nucleus
      through constrictions and overcome the mechanical resistance from deformation of
      the nucleus and the constrictions. The nucleus is treated as an elastic shell
      encompassing a poroelastic material representing the nuclear envelope and inner
      nucleoplasm, respectively. Tuning the chemomechanical parameters of different
      components such as cell contractility and nuclear and matrix stiffnesses, our
      model predicts the lower bounds of constriction size for successful
      transmigration. Furthermore, treating the chromatin as a plastic material, our
      model faithfully reproduced the experimentally observed irreversible nuclear
      deformations after transmigration in lamin-A/C-deficient cells, whereas the wild
      type cells show much less plastic deformation. Along with making testable
      predictions, which are in accord with our experiments and existing literature,
      our work provides a realistic framework to assess the biophysical modulators of
      nuclear deformation during cell transmigration.

PMID- 27705782
TI  - Stargazin Modulation of AMPA Receptors.
AB  - Fast excitatory synaptic signaling in the mammalian brain is mediated by AMPA
      type ionotropic glutamate receptors. In neurons, AMPA receptors co-assemble with
      auxiliary proteins, such as stargazin, which can markedly alter receptor
      trafficking and gating. Here, we used luminescence resonance energy transfer
      measurements to map distances between the full-length, functional AMPA receptor
      and stargazin expressed in HEK293 cells and to determine the ensemble structural
      changes in the receptor due to stargazin. In addition, we used single-molecule
      fluorescence resonance energy transfer to study the structural and conformational
      distribution of the receptor and how this distribution is affected by stargazin.
      Our nanopositioning data place stargazin below the AMPA receptor ligand-binding
      domain, where it is well poised to act as a scaffold to facilitate the long-range
      conformational selection observations seen in single-molecule experiments. These
      data support a model of stargazin acting to stabilize or select conformational
      states that favor activation.

PMID- 27705783
TI  - A Switch in Thermal Preference in Drosophila Larvae Depends on Multiple
      Rhodopsins.
AB  - Drosophila third-instar larvae exhibit changes in their behavioral responses to
      gravity and food as they transition from feeding to wandering stages. Using a
      thermal gradient encompassing the comfortable range (18 degrees C to 28 degrees
      C), we found that third-instar larvae exhibit a dramatic shift in thermal
      preference. Early third-instar larvae prefer 24 degrees C, which switches to
      increasingly stronger biases for 18 degrees C-19 degrees C in mid- and late-third
      instar larvae. Mutations eliminating either of two rhodopsins, Rh5 and Rh6, wiped
      out these age-dependent changes in thermal preference. In larvae, Rh5 and Rh6 are
      thought to function exclusively in the light-sensing Bolwig organ. However, the
      Bolwig organ was dispensable for the thermal preference. Rather, Rh5 and Rh6 were
      required in trpA1-expressing neurons in the brain, ventral nerve cord, and body
      wall. Because Rh1 contributes to thermal selection in the comfortable range
      during the early to mid-third-instar stage, fine thermal discrimination depends
      on multiple rhodopsins.

PMID- 27705784
TI  - Hierarchical Size Scaling during Multicellular Growth and Development.
AB  - Multicellular organisms must regulate their growth across the diverse length
      scales of biological organization, but how this growth is controlled from
      organelle to body, while coordinating interdependent functions at each scale,
      remains poorly understood. We utilized the C. elegans worm intestine as a model
      system to identify distinct allometric scaling laws, revealing that the growth of
      individual structures is differentially regulated during development. We show
      that the volume of the nucleolus, a subcellular organelle, is directly
      proportional (isometric) to cell size during larval development. In contrast to
      findings in a variety of other systems, the size of the nucleus grows more slowly
      and is hypoallometric to the cell. We further demonstrate that the relative size
      of the nucleolus, the site of ribosome biogenesis, is predictive of the growth
      rate of the entire worm. These results highlight the importance of subcellular
      size for organism-level function in multicellular organisms.

PMID- 27705781
TI  - Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with
      Disrupted Mitochondrial Distribution in Mature Dendrites.
AB  - Correct mitochondrial distribution is critical for satisfying local energy
      demands and calcium buffering requirements and supporting key cellular processes.
      The mitochondrially targeted proteins Miro1 and Miro2 are important components of
      the mitochondrial transport machinery, but their specific roles in neuronal
      development, maintenance, and survival remain poorly understood. Using mouse
      knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the
      primary regulator of mitochondrial transport in both axons and dendrites. Miro1
      deletion leads to depletion of mitochondria from distal dendrites but not axons,
      accompanied by a marked reduction in dendritic complexity. Disrupting postnatal
      mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a
      progressive loss of distal dendrites and compromises neuronal survival. Thus, the
      local availability of mitochondrial mass is critical for generating and
      sustaining dendritic arbors, and disruption of mitochondrial distribution in
      mature neurons is associated with neurodegeneration.

PMID- 27705786
TI  - Acetylation Is Crucial for p53-Mediated Ferroptosis and Tumor Suppression.
AB  - Although previous studies indicate that loss of p53-mediated cell cycle arrest,
      apoptosis, and senescence does not completely abrogate its tumor suppression
      function, it is unclear how the remaining activities of p53 are regulated. Here,
      we have identified an acetylation site at lysine K98 in mouse p53 (or K101 for
      human p53). Whereas the loss of K98 acetylation (p53K98R) alone has very modest
      effects on p53-mediated transactivation, simultaneous mutations at all four
      acetylation sites (p534KR: K98R+ 3KR[K117R+K161R+K162R]) completely abolish its
      ability to regulate metabolic targets, such as TIGAR and SLC7A11. Notably, in
      contrast to p533KR, p534KR is severely defective in suppressing tumor growth in
      mouse xenograft models. Moreover, p534KR is still capable of inducing the p53
      Mdm2 feedback loop, but p53-dependent ferroptotic responses are markedly
      abrogated. Together, these data indicate the critical role of p53 acetylation in
      ferroptotic responses and its remaining tumor suppression activity.

PMID- 27705792
TI  - Deciphering the Innate Lymphoid Cell Transcriptional Program.
AB  - Innate lymphoid cells (ILCs) are enriched at mucosal surfaces, where they provide
      immune surveillance. All ILC subsets develop from a common progenitor that gives
      rise to pre-committed progenitors for each of the ILC lineages. Currently, the
      temporal control of gene expression that guides the emergence of these
      progenitors is poorly understood. We used global transcriptional mapping to
      analyze gene expression in different ILC progenitors. We identified PD-1 to be
      specifically expressed in PLZF+ ILCp and revealed that the timing and order of
      expression of the transcription factors NFIL3, ID2, and TCF-1 was critical.
      Importantly, induction of ILC lineage commitment required only transient
      expression of NFIL3 prior to ID2 and TCF-1 expression. These findings highlight
      the importance of the temporal program that permits commitment of progenitors to
      the ILC lineage, and they expand our understanding of the core transcriptional
      program by identifying potential regulators of ILC development.

PMID- 27705787
TI  - Non-canonical PI3K-Cdc42-Pak-Mek-Erk Signaling Promotes Immune-Complex-Induced
      Apoptosis in Human Neutrophils.
AB  - Neutrophils are peripheral blood leukocytes that represent the first line of
      immune cell defense against bacterial and fungal infections but are also crucial
      players in the generation of the inflammatory response. Many neutrophil cell
      surface receptors regulate important cellular processes via activation of agonist
      activated PI3Ks. We show here that activation of human neutrophils with insoluble
      immune complexes drives a previously uncharacterized, PI3K-dependent, non
      canonical, pro-apoptotic signaling pathway, FcgammaR-PI3Kbeta/delta-Cdc42-Pak-Mek
      Erk. This is a rare demonstration of Ras/Raf-independent activation of Erk and of
      PI3K-mediated activation of Cdc42. In addition, comparative analysis of immune
      complex- and fMLF-induced signaling uncovers key differences in pathways used by
      human and murine neutrophils. The non-canonical pathway we identify in this study
      may be important for the resolution of inflammation in chronic inflammatory
      diseases that rely on immune-complex-driven neutrophil activation.

PMID- 27705793
TI  - A Thymic Epithelial Stem Cell Pool Persists throughout Ontogeny and Is Modulated
      by TGF-beta.
AB  - Adult tissue-specific stem cells (SCs) mediate tissue homeostasis and
      regeneration and can give rise to all lineages in the corresponding tissue,
      similar to the early progenitors that generate organs in the first place.
      However, the developmental origins of adult SCs are largely unknown. We recently
      identified thymosphere-forming stem cells (TSFCs) in the adult mouse thymus,
      which display genuine stemness features and can generate the two major thymic
      epithelial cell lineages. Here, we show that embryonic TSFCs possess stemness
      features but differ from adult TSFCs in surface marker profile. Our findings
      support the model of a continuous thymic SC lineage that is maintained throughout
      ontogeny. TGF-beta signaling differentially affects embryonic versus adult
      thymosphere formation, suggesting that thymic epithelial SC potency depends on
      both developmental stage and environmental signals. Collectively, our findings
      suggest that embryonic TSFCs contribute to an adult SC pool and that TSFC
      plasticity is controlled by TGF-beta signaling.

PMID- 27705791
TI  - Association of a Network of Interferon-Stimulated Genes with a Locus Encoding a
      Negative Regulator of Non-conventional IKK Kinases and IFNB1.
AB  - Functional genomic analysis of gene expression in mice allowed us to identify a
      quantitative trait locus (QTL) linked in trans to the expression of 190 gene
      transcripts and in cis to the expression of only two genes, one of which was
      Ypel5. Most of the trans-expression QTL genes were interferon-stimulated genes
      (ISGs), and their expression in mouse macrophage cell lines was stimulated in an
      IFNB1-dependent manner by Ypel5 silencing. In human HEK293T cells, YPEL5
      silencing enhanced the induction of IFNB1 by pattern recognition receptors and
      phosphorylation of TBK1/IKBKE kinases, whereas co-immunoprecipitation experiments
      revealed that YPEL5 interacted physically with IKBKE. We thus found that the
      Ypel5 gene (contained in a locus linked to a network of ISGs in mice) is a
      negative regulator of IFNB1 production and innate immune responses that interacts
      functionally and physically with TBK1/IKBKE kinases.

PMID- 27705788
TI  - Self-Antigen-Driven Thymic B Cell Class Switching Promotes T Cell Central
      Tolerance.
AB  - B cells are unique antigen-presenting cells because their antigen presentation
      machinery is closely tied to the B cell receptor. Autoreactive thymic B cells can
      efficiently present cognate self-antigens to mediate CD4+ T cell-negative
      selection. However, the nature of thymocyte-thymic B cell interaction and how
      this interaction affects the selection of thymic B cell repertoire and, in turn,
      the T cell repertoire are not well understood. Here we demonstrate that a large
      percentage of thymic B cells have undergone class switching intrathymically.
      Thymic B cell class switching requires cognate interaction with specific T cells.
      Class-switched thymic B cells have a distinct repertoire compared with unswitched
      thymic B cells or splenic B cells. Particularly, autoreactive B cell
      specificities preferentially expand in the thymus by undergoing class switching,
      and these enriched, class-switched autoreactive thymic B cells play an important
      role in CD4 T cell tolerance.

PMID- 27705785
TI  - DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control
      Definitive Endoderm Differentiation of Embryonic Stem Cells.
AB  - Long noncoding RNAs (lncRNAs) exhibit diverse functions, including regulation of
      development. Here, we combine genome-wide mapping of SMAD3 occupancy with
      expression analysis to identify lncRNAs induced by activin signaling during
      endoderm differentiation of human embryonic stem cells (hESCs). We find that
      DIGIT is divergent to Goosecoid (GSC) and expressed during endoderm
      differentiation. Deletion of the SMAD3-occupied enhancer proximal to DIGIT
      inhibits DIGIT and GSC expression and definitive endoderm differentiation.
      Disruption of the gene encoding DIGIT and depletion of the DIGIT transcript
      reveal that DIGIT is required for definitive endoderm differentiation. In
      addition, we identify the mouse ortholog of DIGIT and show that it is expressed
      during development and promotes definitive endoderm differentiation of mouse
      ESCs. DIGIT regulates GSC in trans, and activation of endogenous GSC expression
      is sufficient to rescue definitive endoderm differentiation in DIGIT-deficient
      hESCs. Our study defines DIGIT as a conserved noncoding developmental regulator
      of definitive endoderm.

PMID- 27705798
TI  - MyoD Regulates Skeletal Muscle Oxidative Metabolism Cooperatively with
      Alternative NF-kappaB.
AB  - MyoD is a key regulator of skeletal myogenesis that directs contractile protein
      synthesis, but whether this transcription factor also regulates skeletal muscle
      metabolism has not been explored. In a genome-wide ChIP-seq analysis of skeletal
      muscle cells, we unexpectedly observed that MyoD directly binds to numerous
      metabolic genes, including those associated with mitochondrial biogenesis, fatty
      acid oxidation, and the electron transport chain. Results in cultured cells and
      adult skeletal muscle confirmed that MyoD regulates oxidative metabolism through
      multiple transcriptional targets, including PGC-1beta, a master regulator of
      mitochondrial biogenesis. We find that PGC-1beta expression is cooperatively
      regulated by MyoD and the alternative NF-kappaB signaling pathway. Bioinformatics
      evidence suggests that this cooperativity between MyoD and NF-kappaB extends to
      other metabolic genes as well. Together, these data identify MyoD as a regulator
      of the metabolic capacity of mature skeletal muscle to ensure that sufficient
      energy is available to support muscle contraction.

PMID- 27705795
TI  - MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate
      Neurogenesis.
AB  - The generation of neurons from neural stem cells requires large-scale changes in
      gene expression that are controlled to a large extent by proneural transcription
      factors, such as Ascl1. While recent studies have characterized the
      differentiation genes activated by proneural factors, less is known on the
      mechanisms that suppress progenitor cell identity. Here, we show that Ascl1
      induces the transcription factor MyT1 while promoting neuronal differentiation.
      We combined functional studies of MyT1 during neurogenesis with the
      characterization of its transcriptional program. MyT1 binding is associated with
      repression of gene transcription in neural progenitor cells. It promotes neuronal
      differentiation by counteracting the inhibitory activity of Notch signaling at
      multiple levels, targeting the Notch1 receptor and many of its downstream
      targets. These include regulators of the neural progenitor program, such as Hes1,
      Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously
      via MyT1, coupling neuronal differentiation with repression of the progenitor
      fate.

PMID- 27705789
TI  - Type I Interferons Regulate Immune Responses in Humans with Blood-Stage
      Plasmodium falciparum Infection.
AB  - The development of immunoregulatory networks is important to prevent disease.
      However, these same networks allow pathogens to persist and reduce vaccine
      efficacy. Here, we identify type I interferons (IFNs) as important regulators in
      developing anti-parasitic immunity in healthy volunteers infected for the first
      time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell
      function and parasitic-specific CD4+ T cell IFNgamma production, and they
      promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells.
      Type I IFN-dependent, parasite-specific IL-10 production was also observed in P.
      falciparum malaria patients in the field following chemoprophylaxis. Parasite
      induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after
      drug treatment were positively associated with parasite burdens before anti
      parasitic drug administration. These findings have important implications for
      understanding the development of host immune responses following blood-stage P.
      falciparum infection, and they identify type I IFNs and related signaling
      pathways as potential targets for therapies or vaccine efficacy improvement.

PMID- 27705794
TI  - Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production.
AB  - Vitamin D insufficiency is a worldwide epidemic affecting billions of
      individuals, including pregnant women and children. Despite its high incidence,
      the impact of active vitamin D3 (1,25(OH)D3) on embryonic development beyond
      osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OH)D3
      availability modulates zebrafish hematopoietic stem and progenitor cell (HSPC)
      production. Loss of Cyp27b1-mediated biosynthesis or vitamin D receptor (VDR)
      function by gene knockdown resulted in significantly reduced runx1 expression and
      Flk1+cMyb+ HSPC numbers. Selective modulation in vivo and in vitro in zebrafish
      indicated that vitamin D3 acts directly on HSPCs, independent of calcium
      regulation, to increase proliferation. Notably, ex vivo treatment of human HSPCs
      with 1,25(OH)D3 also enhanced hematopoietic colony numbers, illustrating
      conservation across species. Finally, gene expression and epistasis analysis
      indicated that CXCL8(IL-8) was a functional target of vitamin D3-mediated HSPC
      regulation. Together, these findings highlight the relevance of developmental
      1,25(OH)D3 availability for definitive hematopoiesis and suggest potential
      therapeutic utility in HSPC expansion.

PMID- 27705797
TI  - S6K1 Is Required for Increasing Skeletal Muscle Force during Hypertrophy.
AB  - Loss of skeletal muscle mass and force aggravates age-related sarcopenia and
      numerous pathologies, such as cancer and diabetes. The AKT-mTORC1 pathway plays a
      major role in stimulating adult muscle growth; however, the functional role of
      its downstream mediators in vivo is unknown. Here, we show that simultaneous
      inhibition of mTOR signaling to both S6K1 and 4E-BP1 is sufficient to reduce AKT
      induced muscle growth and render it insensitive to the mTORC1-inhibitor
      rapamycin. Surprisingly, lack of mTOR signaling to 4E-BP1 only, or deletion of
      S6K1 alone, is not sufficient to reduce muscle hypertrophy or alter its
      sensitivity to rapamycin. However, we report that, while not required for muscle
      growth, S6K1 is essential for maintaining muscle structure and force production.
      Hypertrophy in the absence of S6K1 is characterized by compromised ribosome
      biogenesis and the formation of p62-positive protein aggregates. These findings
      identify S6K1 as a crucial player for maintaining muscle function during
      hypertrophy.

PMID- 27705796
TI  - VEGF-A/Notch-Induced Podosomes Proteolyse Basement Membrane Collagen-IV during
      Retinal Sprouting Angiogenesis.
AB  - During angiogenic sprouting, endothelial tip cells emerge from existing vessels
      in a process that requires vascular basement membrane degradation. Here, we show
      that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes
      contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation
      of functional podosomes in endothelial cells. Using a retinal neovascularization
      model, we demonstrate that tip cells assemble podosomes during physiological
      angiogenesis in vivo. In the retina, podosomes are also part of an interconnected
      network that surrounds large microvessels and impinges on the underlying basement
      membrane. Consistently, collagen-IV is scarce in podosome areas. Moreover, Notch
      inhibition exacerbates podosome formation and collagen-IV loss. We propose that
      the localized proteolytic action of podosomes on basement membrane collagen-IV
      facilitates endothelial cell sprouting and anastomosis within the developing
      vasculature. The identification of podosomes as key components of the sprouting
      machinery provides another opportunity to target angiogenesis therapeutically.

PMID- 27705800
TI  - PAXX Is an Accessory c-NHEJ Factor that Associates with Ku70 and Has Overlapping
      Functions with XLF.
AB  - In mammalian cells, classical non-homologous end joining (c-NHEJ) is critical for
      DNA double-strand break repair induced by ionizing radiation and during V(D)J
      recombination in developing B and T lymphocytes. Recently, PAXX was identified as
      a c-NHEJ core component. We report here that PAXX-deficient cells exhibit a
      cellular phenotype uncharacteristic of a deficiency in c-NHEJ core components.
      PAXX-deficient cells display normal sensitivity to radiomimetic drugs, are
      proficient in transient V(D)J recombination assays, and do not shift toward
      higher micro-homology usage in plasmid repair assays. Although PAXX-deficient
      cells lack c-NHEJ phenotypes, PAXX forms a stable ternary complex with Ku bound
      to DNA. Formation of this complex involves an interaction with Ku70 and requires
      a bare DNA extension for stability. Moreover, the relatively weak Ku-dependent
      stimulation of LIG4/XRCC4 activity by PAXX is unmasked by XLF ablation. Thus,
      PAXX plays an accessory role during c-NHEJ that is largely overlapped by XLF's
      function.

PMID- 27705799
TI  - Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise
      Intolerance in Mice.
AB  - We recently identified human N-acetyltransferase 2 (NAT2) as an insulin
      resistance (IR) gene. Here, we examine the cellular mechanism linking NAT2 to IR
      and find that Nat1 (mouse ortholog of NAT2) is co-regulated with key
      mitochondrial genes. RNAi-mediated silencing of Nat1 led to mitochondrial
      dysfunction characterized by increased intracellular reactive oxygen species and
      mitochondrial fragmentation as well as decreased mitochondrial membrane
      potential, biogenesis, mass, cellular respiration, and ATP generation. These
      effects were consistent in 3T3-L1 adipocytes, C2C12 myoblasts, and in tissues
      from Nat1-deficient mice, including white adipose tissue, heart, and skeletal
      muscle. Nat1-deficient mice had changes in plasma metabolites and lipids
      consistent with a decreased ability to utilize fats for energy and a decrease in
      basal metabolic rate and exercise capacity without altered thermogenesis.
      Collectively, our results suggest that Nat1 deficiency results in mitochondrial
      dysfunction, which may constitute a mechanistic link between this gene and IR.

PMID- 27705790
TI  - HIV Triggers a cGAS-Dependent, Vpu- and Vpr-Regulated Type I Interferon Response
      in CD4+ T Cells.
AB  - Several pattern-recognition receptors sense HIV-1 replication products and induce
      type I interferon (IFN-I) production under specific experimental conditions.
      However, it is thought that viral sensing and IFN induction are virtually absent
      in the main target cells of HIV-1 in vivo. Here, we show that activated CD4+ T
      cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a
      bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection
      requires proviral integration and is regulated by newly expressed viral accessory
      proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction.
      Furthermore, Vpr also amplifies innate sensing of HIV-1 infection in Vpx-treated
      dendritic cells. Our results identify cGAS as mediator of an IFN-I response to
      HIV-1 infection in CD4+ T cells and demonstrate that this response is modulated
      by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is
      incomplete in the main target cells of HIV-1.

PMID- 27705801
TI  - Robust Replication Control Is Generated by Temporal Gaps between Licensing and
      Firing Phases and Depends on Degradation of Firing Factor Sld2.
AB  - Temporal separation of DNA replication initiation into licensing and firing
      phases ensures the precise duplication of the genome during each cell cycle.
      Cyclin-dependent kinase (CDK) is known to generate this separation by activating
      firing factors and at the same time inhibiting licensing factors but may not be
      sufficient to ensure robust separation at transitions between both phases. Here,
      we show that a temporal gap separates the inactivation of firing factors from the
      re-activation of licensing factors during mitosis in budding yeast. We find that
      gap size critically depends on phosphorylation-dependent degradation of the
      firing factor Sld2 mediated by CDK, DDK, Mck1, and Cdc5 kinases and the ubiquitin
      ligases Dma1/2. Stable mutants of Sld2 minimize the gap and cause increased
      genome instability in an origin-dependent manner when combined with deregulation
      of other replication regulators or checkpoint mechanisms. Robust separation of
      licensing and firing phases therefore appears indispensable to safeguard genome
      stability.

PMID- 27705806
TI  - Condensin and Hmo1 Mediate a Starvation-Induced Transcriptional Position Effect
      within the Ribosomal DNA Array.

PMID- 27705809
TI  - The effect of lead contamination on bioturbation by Lumbriculus variegatus in a
      freshwater microcosm.
AB  - The present study investigated the effect of lead (Pb) on bioturbation by the
      oligochaete worm Lumbriculus variegatus, using freshwater microcosms. The
      experiment used lead at "0", 140, 700, and 3500 MUg/g in sediment, and used two
      different laboratory populations of L. variegatus. A molecular genetic analysis
      and bioassays were conducted to determine if the two populations differed
      genetically and whether they differed in Pb-sensitivity. The bioturbation of L.
      variegatus was estimated using luminophores placed at the sediment-water
      interface at the beginning of the experiment. After the 14 d experiment the
      luminophore profiles in sediment were used to estimate the biodiffusion and
      bioadvection coefficients, using the diffusion-advection model. The results
      showed that the biodiffusion and bioadvection coefficients were generally
      negatively related to the Pb concentrations in the sediment. Lead at 700 and 3500
      MUg/g reduced both coefficients, while Pb at 140 MUg/g did not. Luminophore
      profiles in the "0" and 140 MUg/g treatments were indicative of a non-local
      transport, while a diffusive transport was observed at the higher Pb levels. The
      two laboratory populations of L. variegatus used in the experiment differed in
      their sensitivity to Pb when mortality was used as the endpoint, but they did not
      differ in sediment bioturbation or the Pb-sensitivity of this process. Moreover,
      the genetic analysis did not detect any genetic differences between the
      populations. This study demonstrated that elevated levels of Pb can impact
      ecosystem functioning by decreasing the bioturbation activity of benthic
      organisms such as L. variegatus.

PMID- 27705803
TI  - A High-Density Map for Navigating the Human Polycomb Complexome.
AB  - Polycomb group (PcG) proteins are major determinants of gene silencing and
      epigenetic memory in higher eukaryotes. Here, we systematically mapped the human
      PcG complexome using a robust affinity purification mass spectrometry approach.
      Our high-density protein interaction network uncovered a diverse range of PcG
      complexes. Moreover, our analysis identified PcG interactors linking them to the
      PcG system, thus providing insight into the molecular function of PcG complexes
      and mechanisms of recruitment to target genes. We identified two human PRC2
      complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N
      acetylglucosamine transferase OGT1 and several transcription factors. Finally,
      genome-wide profiling of PR-DUB components indicated that the human PR-DUB and
      PRC1 complexes bind distinct sets of target genes, suggesting differential impact
      on cellular processes in mammals.

PMID- 27705808
TI  - Oxidative stress intensity-related effects of cadmium (Cd) and paraquat (PQ) on
      UV-damaged-DNA binding and excision repair activities in zebrafish (Danio rerio)
      embryos.
AB  - Our earlier studies showed the inhibitory effects of cadmium (Cd) and paraquat
      (PQ) on the gene expression of DNA mismatch recognition proteins in zebrafish
      (Danio rerio) embryos. This study explored the effects of Cd and PQ on nucleotide
      excision repair (NER) capacity in zebrafish embryos. Exposure of embryos at 1 h
      post fertilization (hpf) to 3-5 MUM Cd or 30-100 MUM PQ for 9 h induced a 2-3
      fold increase of oxidative stress, while a 6.5-fold increase of oxidative stress
      was induced by 200 MUM PQ. Real-time RT-PCR detected a down-regulated xeroderma
      pigmentosum C (XPC) and an up-regulated UV-DDB2 gene expression in mildly
      stressed embryos, whereas 8-oxoguanine DNA glycosylase (OGG1) gene expression
      increased with PQ exposure levels. NER of UV-damaged DNA was enhanced in weakly
      oxidant-stressed embryos as shown by a transcription-based DNA repair assay, yet
      repair activities of both UV and cisplatin-damaged DNA were inhibited in embryos
      exposed to 200 MUM PQ. Band shift assay showed a suppression of cyclobutane
      pyrimidine dimer (CPD) binding activity in all stressed embryos. In contrast, (6
      4) photoproduct (6-4PP) recognition activity was weakly stimulated except in
      embryos exposed to 200 MUM PQ, revealing a link of NER capacity to 6-4PP binding.
      Our results showed that Cd and PQ imposed similar inducing effects on UV-DDB2
      gene expression, NER of UV-damaged DNA and 6-4PP binding activity in zebrafish
      embryo under low levels of oxidative stress and NER capacity could be inhibited
      if the intensity of oxidative stress increased to a critical level.

PMID- 27705807
TI  - A passive sampling method for assessing the occurrence and risk of
      organophosphate flame retardants in aquatic environments.
AB  - A modified polar organic chemical integrative sampler (m-POCIS) was used to
      determine the occurrence of and risk posed by organophosphate flame retardants
      (OPFRs) in the Yangtze River in Nanjing. Laboratory calibrations were performed
      to determine sampling rates (Rs) in different situations. Rs values increased
      with the flow rate, but the effect of dissolved organic matter (DOM) on Rs was
      relatively small. The validation of Rs in the m-POCIS for 15 days at the Yangtze
      River in 2015 showed that the Rs values for most of the test compounds are
      considerably larger than those obtained in the laboratory. The aqueous
      concentrations of OPFRs were estimated by using Rs values obtained in the field.
      OPFRs were widely distributed in the Yangtze River, with total concentrations as
      determined by the m-POCIS ranging from 44.95 ng/L to 118.38 ng/L. These suggest
      their widespread use and persistence in the river. This study also provided a
      protocol for the assessment of risk posed by OPFRs. It showed that tripentyl
      phosphate (TPeP) could pose medium risk to daphnia in the Yangtze River.

PMID- 27705810
TI  - Organic complexation of copper in throughfall and open field bulk deposition:
      Influence of the tree canopy of Mediterranean forest ecosystems.
AB  - The complexing capacity for Cu ions (LT) and the apparent stability constant
      values (logKapp) were measured in throughfall (TF) and open field bulk deposition
      (BD), at two Mediterranean forest ecosystems of western Greece. LT was measured
      for the first time in the TF of natural forests. Concentrations of LT were three
      to-four-fold higher in TF (mean +/- st.dev: 2014 +/- 769 nM for Varetada and 1565
      +/- 595 nM for Karpenissi) compared to those in BD (531 +/- 517 nM and 468 +/-
      321 nM, respectively). In all TF and BD samples, LT concentrations were
      significantly higher than the corresponding total Cu concentrations, indicating
      that Cu was fully complexed. The LT/TOC ratios in TF were found comparable
      between the two study sites (235 +/- 149 nM mg-1 C for Varetada and 256 +/- 233
      nM mg-1 C for Karpenissi) and with those of BD (226 +/- 257 and 163 +/- 163 nM mg
      1 C, respectively). The determined mean logKapp values were almost identical in
      TF (6.8 +/- 0.7 at Varetada; 6.8 +/- 0.6 at Karpenissi) and BD (6.5 +/- 0.6 at
      Varetada; 6.8 +/- 0.3 at Karpenissi), pointing to the fact that regardless of the
      enrichment of TF in ligands (LT(TF) > LT(BD)) the type of binding sites remain
      the same. The logKapp values which were obtained herewith are similar to those
      obtained for humic-like substances (HULIS), indicating them as the most
      widespread type of ligands in BD and TF.

PMID- 27705812
TI  - Ligand-Driven T Cell Receptor Selection in Celiac Disease.
AB  - Recognition of antigens by T cell receptors (TCRs) underlies cellular immunity.
      By comparing how different TCRs recognize the key antigens associated with celiac
      disease, Petersen et al. (2016), in this issue of Structure, show how celiac
      antigen properties select immunologically distinct yet structurally and
      physically compatible TCRs, ultimately driving autoimmunity.

PMID- 27705814
TI  - Distinct Signaling Roles of cIMP, cCMP, and cUMP.
AB  - The cyclic purine nucleotide cIMP and the cyclic pyrimidine nucleotides cCMP and
      cUMP are emerging second messengers. These cNMPs show different biological
      effects, but the molecular mechanisms remain elusive. In this issue of Structure,
      Ng et al. (2016) provide structural evidence for distinct interactions of cIMP,
      cCMP, and cUMP with ion channels.

PMID- 27705815
TI  - Structure of the Pseudomonas aeruginosa Type IVa Pilus Secretin at 7.4 A.
AB  - Type IVa pili (T4aP) function as bacterial virulence factors. T4aP pass through
      the outer membranes of Gram-negative bacteria via homo-oligomeric secretins. We
      present a 7.4 A cryoelectron microscopy structure of the Pseudomonas aeruginosa
      PilQ secretin. Peripheral and internal features show that the secretin is
      composed of 14 subunits with C7 symmetry. The channel is a ribbed cylinder with
      central peripheral spokes and a central gate closed on the periplasmic side. The
      structure suggests that during pilus extrusion, the central gate is displaced to
      the interior walls and that no additional conformational changes are required, as
      the internal diameter can accommodate the pilus. The N1 domain was resolved,
      while the N0 and the N-terminal beta-domains proposed to bind peptidoglycan were
      absent in class average images and the final 3D map, indicating a high
      flexibility. These data provide the highest-resolution structure to date of a
      T4aP secretin.

PMID- 27705804
TI  - Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome
      wide DNA Methylation Profiling.
AB  - Aberrant DNA methylation patterns in malignant cells allow insight into tumor
      evolution and development and can be used for disease classification. Here, we
      describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+)
      and NPM-ALK-negative (ALK-) anaplastic large-cell lymphoma (ALCL). We find that
      ALK+ and ALK- ALCL share common DNA methylation changes for genes involved in T
      cell differentiation and immune response, including TCR and CTLA-4, without an
      ALK-specific impact on tumor DNA methylation in gene promoters. Furthermore, we
      uncover a close relationship between global ALCL DNA methylation patterns and
      those in distinct thymic developmental stages and observe tumor-specific DNA
      hypomethylation in regulatory regions that are enriched for conserved
      transcription factor binding motifs such as AP1. Our results indicate similarity
      between ALCL tumor cells and thymic T cell subsets and a direct relationship
      between ALCL oncogenic signaling and DNA methylation through transcription factor
      induction and occupancy.

PMID- 27705805
TI  - Transcriptional Profiling Reveals a Common Metabolic Program in High-Risk Human
      Neuroblastoma and Mouse Neuroblastoma Sphere-Forming Cells.
AB  - High-risk neuroblastoma remains one of the deadliest childhood cancers.
      Identification of metabolic pathways that drive or maintain high-risk
      neuroblastoma may open new avenues of therapeutic interventions. Here, we report
      the isolation and propagation of neuroblastoma sphere-forming cells with self
      renewal and differentiation potential from tumors of the TH-MYCN mouse, an animal
      model of high-risk neuroblastoma with MYCN amplification. Transcriptional
      profiling reveals that mouse neuroblastoma sphere-forming cells acquire a
      metabolic program characterized by transcriptional activation of the cholesterol
      and serine-glycine synthesis pathways, primarily as a result of increased
      expression of sterol regulatory element binding factors and Atf4, respectively.
      This metabolic reprogramming is recapitulated in high-risk human neuroblastomas
      and is prognostic for poor clinical outcome. Genetic and pharmacological
      inhibition of the metabolic program markedly decreases the growth and
      tumorigenicity of both mouse neuroblastoma sphere-forming cells and human
      neuroblastoma cell lines. These findings suggest a therapeutic strategy for
      targeting the metabolic program of high-risk neuroblastoma.

PMID- 27705816
TI  - Beyond the survival and death of the deltamethrin-threatened pollen beetle
      Meligethes aeneus: An in-depth proteomic study employing a transcriptome
      database.
AB  - : Insecticide resistance is an increasingly global problem that hampers pest
      control. We sought the mechanism responsible for survival following pyrethroid
      treatment and the factors connected to paralysis/death of the pollen beetle
      Meligethes aeneus through a proteome-level analysis using nanoLC coupled with
      Orbitrap FusionTM TribridTM mass spectrometry. A tolerant field population of
      beetles was treated with deltamethrin, and the ensuing proteome changes were
      observed in the survivors (resistant), dead (paralyzed) and control-treated
      beetles. The protein database consisted of the translated transcriptome, and the
      resulting changes were manually annotated via BLASTP. We identified a number of
      high-abundance changes in which there were several dominant proteins, e.g., the
      electron carrier cytochrome b5, ribosomal proteins 60S RPL28, 40S RPS23 and
      RPS26, eIF4E-transporter, anoxia up-regulated protein, 2 isoforms of vitellogenin
      and pathogenesis-related protein 5. Deltamethrin detoxification was influenced by
      different cytochromes P450, which were likely boosted by increased cytochrome b5,
      but glutathione-S-transferase epsilon and UDP-glucuronosyltransferases also
      contributed. Moreover, we observed changes in proteins related to RNA
      interference, RNA binding and epigenetic modifications. The high changes in
      ribosomal proteins and associated factors suggest specific control of
      translation. Overall, we showed modulation of expression processes by epigenetic
      markers, alternative splicing and translation. Future functional studies will
      benefit. BIOLOGICAL SIGNIFICANCE: Insects develop pesticide resistance, which has
      become one of the key issues in plant protection. This growing resistance
      increases the demand for pesticide applications and the development of new
      substances. Knowledge in the field regarding the resistance mechanism and its
      responses to pesticide treatment provides us the opportunity to propose a
      solution for this issue. Although the pollen beetle Meligethes aeneus was
      effectively controlled with pyrethroids for many years, there have been reports
      of increasing resistance. We show protein changes including production of
      isoforms in response to deltamethrin at the protein level. These results
      illustrate the insect's survival state as a resistant beetle and in its paralyzed
      state (evaluated as dead) relative to resistant individuals.

PMID- 27705818
TI  - Treatment of groundwater containing Mn(II), Fe(II), As(III) and Sb(III) by
      bioaugmented quartz-sand filters.
AB  - High concentrations of iron (Fe(II)) and manganese (Mn(II)) often occur
      simultaneously in groundwater. Previously, we demonstrated that Fe(II) and Mn(II)
      could be oxidized to biogenic Fe-Mn oxides (BFMO) via aeration and microbial
      oxidation, and the formed BFMO could further oxidize and adsorb other pollutants
      (e.g., arsenic (As(III)) and antimony (Sb(III))). To apply this finding to
      groundwater remediation, we established four quartz-sand columns for treating
      groundwater containing Fe(II), Mn(II), As(III), and Sb(III). A Mn-oxidizing
      bacterium (Pseudomonas sp. QJX-1) was inoculated into two parallel bioaugmented
      columns. Long-term treatment (120 d) showed that bioaugmentation accelerated the
      formation of Fe-Mn oxides, resulting in an increase in As and Sb removal. The
      bioaugmented columns also exhibited higher overall treatment effect and anti
      shock load capacity than that of the non-bioaugmented columns. To clarify the
      causal relationship between the microbial community and treatment effect, we
      compared the biomass of active bacteria (reverse-transcribed real-time PCR),
      bacterial community composition (Miseq 16S rRNA sequencing) and community
      function (metagenomic sequencing) between the bioaugmented and non-bioaugmented
      columns. Results indicated that the QJX1 strain grew steadily and attached onto
      the filter material surface in the bioaugmented columns. In general, the
      inoculated strain did not significantly alter the composition of the indigenous
      bacterial community, but did improve the relative abundances of xenobiotic
      metabolism genes and Mn oxidation gene. Thus, bioaugmentation intensified
      microbial degradation/utilization for the direct removal of pollutants and
      increased the formation of Fe-Mn oxides for the indirect removal of pollutants.
      Our study provides an alternative method for the treatment of groundwater
      containing high Fe(II), Mn(II) and As/Sb.

PMID- 27705802
TI  - Cytosolic Accumulation of L-Proline Disrupts GABA-Ergic Transmission through GAD
      Blockade.
AB  - Proline dehydrogenase (PRODH), which degrades L-proline, resides within the
      schizophrenia-linked 22q11.2 deletion suggesting a role in disease. Supporting
      this, elevated L-proline levels have been shown to increase risk for psychotic
      disorders. Despite the strength of data linking PRODH and L-proline to
      neuropsychiatric diseases, targets of disease-relevant concentrations of L
      proline have not been convincingly described. Here, we show that Prodh-deficient
      mice with elevated CNS L-proline display specific deficits in high-frequency GABA
      ergic transmission and gamma-band oscillations. We find that L-proline is a GABA
      mimetic and can act at multiple GABA-ergic targets. However, at disease-relevant
      concentrations, GABA-mimesis is limited to competitive blockade of glutamate
      decarboxylase leading to reduced GABA production. Significantly, deficits in GABA
      ergic transmission are reversed by enhancing net GABA production with the
      clinically relevant compound vigabatrin. These findings indicate that
      accumulation of a neuroactive metabolite can lead to molecular and synaptic
      dysfunction and help to understand mechanisms underlying neuropsychiatric
      disease.

PMID- 27705813
TI  - AXIN Shapes Tankyrase ARChitecture.
AB  - The poly(ADP-ribose)polymerase (PARP) Tankyrase uses ankyrin repeat modules to
      capture substrates via Tankyrase-binding peptide motifs. In this issue of
      Structure, Eisemann et al. (2016) describe how the signaling protein AXIN can
      access and conformationally adapt the multivalent ankyrin repeat region of
      Tankyrase and discuss potential implications for enzymatic substrate
      modification.

PMID- 27705817
TI  - Peptidomics of the zebrafish Danio rerio: In search for neuropeptides.
AB  - : (Neuro)peptides are small messenger molecules that are derived from larger,
      inactive precursor proteins by the highly controlled action of processing
      enzymes. These biologically active peptides can be found in all metazoan species
      where they orchestrate a wide variety of physiological processes. Obviously,
      detailed knowledge on the actual peptide sequences, including the potential
      existence of truncated versions or presence of post-translation modifications, is
      of high importance when studying their function. A peptidomics approach therefore
      aims to identify and characterize the endogenously present peptide complement of
      a defined tissue or organism using liquid chromatography and mass spectrometry.
      While the zebrafish Danio rerio is considered as an important aquatic model for
      medical research, neuroscience, development and ecotoxicology, very little is
      known about their peptidergic signaling cascades. We therefore set out to
      biochemically characterize endogenously present (neuro)peptides from the
      zebrafish brain. This peptidomics setup yielded >60 different peptides in
      addition to various truncated versions. SIGNIFICANCE: Though the zebrafish is a
      well-established model organism to study vertebrate biology and gene functions in
      either a medical or (eco)toxicological context, very little knowledge about
      neuropeptidergic signaling cascades is available. We therefore set out to
      characterize endogenously present peptides from the zebrafish brain using a
      peptidomics setup yielding a total number of 105 peptide identifications. To our
      knowledge, it is the first attempt to biochemically isolate and characterize
      neuropeptides from a fish species in a high-throughput manner. This archive of
      identified endogenous peptides is likely to aid further functional elucidation of
      defined neuropeptidergic signaling systems (e.g. characterization of cognate G
      protein coupled receptors). Furthermore, our methodology allows studying the
      changes in peptide expression in response to changes in the organism or the
      environment using differential peptidomics.

PMID- 27705819
TI  - Revisiting the association between childhood trauma and psychosis in bipolar
      disorder: A quasi-dimensional path-analysis.
AB  - BACKGROUND: Childhood trauma has been associated with a more severe clinical
      expression of bipolar disorder (BD). However, the results that specifically
      associated traumatic events and psychotic features in BD have been inconsistent,
      possibly due to the low resolution of the phenotypes being used. METHODS: 270
      normothymic patients with BD completed the Childhood Trauma Questionnaire (CTQ)
      and the Peters Delusion Inventory (PDI) that assessed 21 delusional beliefs.
      Patients were characterized for the lifetime presence of psychotic features
      during episodes and cannabis misuse in accordance with DSM-IV. We performed a
      series of path analyses to investigate the links from three types of childhood
      abuse (physical, sexual and emotional) directly to delusional beliefs and
      psychotic features, and indirectly through cannabis misuse. RESULTS: A first path
      analysis showed no link between any of the childhood abuse types and psychotic
      features when only a categorical definition of psychosis was used. When
      incorporating the quasi-dimensional measure of delusional beliefs in a second
      path analysis, we found that emotional and physical abuse and cannabis misuse
      were each directly associated with PDI score. PDI score and psychotic features
      were strongly correlated. Childhood abuse did not operate through cannabis misuse
      to increase delusional beliefs. Including type of BD in the model did not alter
      the results. CONCLUSION: Emotional and physical abuse, but also cannabis misuse,
      increased delusional beliefs in patients with BD. Using a quasi-dimensional
      measure of psychotic symptoms in BD provided higher resolution of the psychosis
      phenotype and helped reconcile ambiguous findings from previous studies.

PMID- 27705820
TI  - Corrigendum to "Formation of a cytoplasmic salt bridge network in the matrix
      state is a fundamental step in the transport mechanism of the mitochondrial
      ADP/ATP carrier" [Biochim. Biophys. Acta 1857 (2016) 14-22].

PMID- 27705811
TI  - Mutagenic potential assessment associated with human exposure to natural
      radioactivity.
AB  - Lucrecia city, known to harbor a high cancer rate, is located in a semiarid
      region characterized by the presence of mineral reservoirs, facing a high
      exposure to metal and natural radioactivity. The present study aimed to assess
      the environmental scenario at a semiarid region located in Northeastern Brazil.
      Metal concentration, alpha and beta radiation, and cyanobacteria content in tap
      water along with indoor radon and gamma emitters (U, K and Th) concentrations
      were measured. In addition, mutagenic and nuclear instability effects were
      assessed using buccal micronucleus cytome assay. The study included five
      samplings corresponding to a period between 2007 and 2009. Drinking water from
      Lucrecia city presented levels of Mn, Ni and Cr along with cyanobacteria in
      concentrations one to four times higher than regulatory guidelines considered.
      Furthermore, high levels of all the tested radionuclides were found. A high
      percentage of the houses included in this study presented indoor radon
      concentrations over 100 Bq m-3. The mean annual effective dose from Lucrecia
      houses was six times higher than observed in a control region. The levels of
      exposure in most of the Lucrecia houses were classified as middle to high. A
      significant mutagenic effect, represented as an increase of micronuclei (MN)
      frequency and nuclear abnormalities as nuclear buds (NB), binucleated cells (BN),
      and pyknotic cells (PYC) were found. The results obtained highlight the role of
      high background radioactivity on the observed mutagenic effect and could help to
      explain the exacerbated cancer rate reported in this locality.

PMID- 27705821
TI  - Corrigendum to "Influence of Histidine-198 of the D1 subunit on the properties of
      the primary electron donor, P680, of photosystem II in Thermosynechococcus
      elongatus".
AB  - Two mutants, D1-H198Q and D1-H198A, have been previously constructed in
      Thermosynechococcus elongatus with the aim at modifying the redox potential of
      the P680*+/P680 couple by changing the axial ligand of PD1, one the two
      chlorophylls of the Photosystem II primary electron donor [Sugiura et al.,
      Biochim. Biophys. Acta 1777 (2008) 331-342]. However, after the publication of
      this work it was pointed out to us by Dr. Eberhard Schlodder (Technische
      Universitat Berlin) that in both mutants the pheophytin band shift which is
      observed upon the reduction of QA was centered at 544nm instead of 547nm, clearly
      showing that the D1 protein corresponded to PsbA1 whereas the mutants were
      supposedly constructed in the psbA3 gene so that the conclusions in our previous
      paper were wrong. O2 evolving mutants have been therefore reconstructed and their
      analyze shows that they are now correct mutants which are suitable for further
      studies. Indeed, the D1-H198Q mutation downshifted by ~3nm the P680*+/P680
      difference absorption spectrum in the Soret region and increased the redox
      potential of the P680*+/P680 couple and the D1-H198A mutation decreased the redox
      potential of the P680*+/P680 couple all these effects being comparable to those
      which were observed in Synechocystis sp. PCC 6803 [Diner et al., Biochemistry 40
      (2001) 9265-9281 and Merry et al. Biochemistry 37 (1998) 17,439-17,447]. We
      apologize for having presented wrong data and wrong conclusions in our earlier
      publication.

PMID- 27705822
TI  - Geochemical investigation of the galvanic effects during oxidation of pyrite and
      base-metals sulfides.
AB  - Predicting the water quality at mine sites is of significant importance for
      developing mines with respect for the environment. Acid mine drainage (AMD)
      occurs when sulfides are in contact with oxygen and water, and several parameters
      and mechanisms influence final drainage quality. Galvanic interactions influence
      the reactivity of sulfide minerals, which act as semi-conductors. These galvanic
      interactions have been insufficiently studied in the context of AMD generation.
      In this study, the influence of pyrite on the reactivity of sphalerite and
      chalcopyrite was investigated. Five blends, comprised of free grains of
      quartz/pyrite, quartz/chalcopyrite, quartz/sphalerite,
      quartz/pyrite/chalcopyrite, and quartz/pyrite/sphalerite, were subjected to
      geochemical testing. Five weathering cells were monitored over a 200-day period
      during which they were leached twice weekly. Leachates were analyzed for pH, Eh,
      electrical conductivity, and sulfate and metal concentrations. The results of
      these analyses showed that galvanic interactions occurred between free sulfide
      grains. Pyrite was galvanically protected over the full testing period in the
      quartz/pyrite/chalcopyrite blend, and partially protected in the
      quartz/pyrite/sphalerite blend. Moreover, the release of Cu from chalcopyrite and
      Zn, Mn, and Cd from sphalerite was accelerated in the presence of pyrite. This
      work provides a better understanding of the influence of pyrite on chalcopyrite
      and sphalerite reactivity by highlighting the galvanic effects. In the future, to
      improve the reliability of AMD prediction tests, galvanic interactions should be
      considered in both the prediction of the acid generation potential and the
      estimation of metal and metalloid release rates.

PMID- 27705823
TI  - Nontargeted detection and identification of (aromatic) amines in environmental
      samples based on diagnostic derivatization and LC-high resolution mass
      spectrometry.
AB  - The presence of aromatic amines in the environment has been in the focus of
      research, as many of these compounds are known or suspected mutagens and
      carcinogens. To facilitate the detection of aromatic amines in complex
      environmental samples by LC-high resolution mass spectrometry, an on-line-post
      column and a pre-column derivatization method to label (in an ideal case) all
      aromatic amines was evaluated by applying different derivatization reagents. 4
      Fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) was found to be the most promising
      labeling reagent due to its high reactivity with both primary and secondary
      amines and its low signal in positive mode electrospray ionization (ESI+). Post
      column on-line derivatization did not result in sufficient signal intensities of
      derivatives. With pre-column derivatization most of the selected aromatic amines
      resulted in a derivative that shows common fragments of diagnostic value. The
      selectivity of NBD-F was studied in depth with a data set of 220 compounds with
      different functional groups showing that also aliphatic amines and some thiols
      yield a derivative. The developed method was successfully applied to wastewater
      effluent samples and several derivatives were confirmed by diagnostic neutral
      losses.

PMID- 27705824
TI  - Use of a chemometric tool to establish the regional background and assess trace
      metal enrichment at Baixada Santista - southeastern Brazil.
AB  - The trace metals in sediments consist of two components, anthropogenic and
      lithogenic or natural, which can cause misinterpretations for what actually
      exists in sediments. Normally, to investigate trace metal background levels,
      indices are applied in order to normalize the values and reduce natural
      variability, but it is well known that using the average shale or crust content
      is not the best choice and vertical sediment profiles are not always available.
      The purpose of this study is to use a prediction interval to assess metal
      enrichment without a reference level and to assess a regional background level
      using the same tool. The levels of eight elements were submitted to a partial
      digestion technique and analyzed by ICP-OES. The enrichment factor results
      suggested that using background values from the prediction interval and using
      values from vertical sediment profiles yield statistically similar results.
      Furthermore, the background equations present more realistic data than other
      methods because they consider the mud content of the samples. Thus, a prediction
      interval can be a useful tool to establish a regional background and assess trace
      metal enrichment.

PMID- 27705825
TI  - Application of mixed effects models for characterizing contaminated sites.
AB  - In a typical data collection process for the purpose of characterizing
      contaminated sites, boreholes are usually drilled in different locations based on
      a sampling plan; and consequently, multiple samples are collected from each
      borehole. As a result, it is quite plausible that a certain degree of dependency
      or similarity exists among observations nested within a borehole. However, when
      classical regression models are employed, such dependencies are often ignored,
      resulting in biased estimates. In site characterization studies, further
      complication arises due to the presence of left-censored observations, those
      falling below the detection limit of measuring instruments. To overcome the above
      issues, this paper employs a mixed effects model that allows accounting for the
      within-borehole data dependency while accommodating left-censored concentrations.
      The benefits of the adopted methodology are explored by analyzing concentration
      data obtained from characterization study of a brownfield site located in
      Montreal, Canada. This paper illustrates that the estimated within-borehole
      correlation can be used to determine the optimal number of boreholes as well as
      the sample size to be collected from each borehole. Such correlation is
      underestimated when censored values are not accommodated in the model but
      substituted with a constant prior to data analysis. In addition, the adopted
      methodology provides an accurate insight into the vertical extent of
      contamination that can result in different compliance decisions when compared
      with classical approach.

PMID- 27705826
TI  - Micro-distribution of arsenic species in tissues of hyperaccumulator Pteris
      vittata L.
AB  - Arsenic (As) contamination and its harmful consequences have gained increasing
      attention in research. Phytoextraction, which uses the As hyperaccumulator Pteris
      vittata L., is a well-established technology adopted in many countries. However,
      the hyperaccumulation mechanisms of this plant remain controversial. This study
      investigated the species and the micro-distribution of As species in three P.
      vittata L. ecotypes after exposure to arsenite (AsIII) and arsenate (AsV) for 7d.
      Arsenic-accumulating abilities and preferences to As species varied among
      different ecotypes. The reduction of AsV into AsIII, oxidation of AsIII into AsV,
      and chelation of AsIII with thiols were all observed in P. vittata. The reduction
      of As mainly occurred in the rhizoid, whereas oxidation and chelation mainly
      occurred in the aboveground parts. Correlation analyses showed that the As
      concentration in pinna was significantly correlated with the AsV percentage in
      paraxial and abaxial epidermis (positive), AsIII-GSH percentage in paraxial
      epidermis (positive), and AsIII percentage in paraxial and abaxial epidermis
      (negative). Results indicated that oxidation and chelation reactions contributed
      to the accumulation of As in P. vittata.

PMID- 27705827
TI  - Analysis of emerging contaminants in water and solid samples using high
      resolution mass spectrometry with a Q Exactive orbital ion trap and estrogenic
      activity with YES-assay.
AB  - Trace emerging contaminants (ECs) occur in both waste and surface waters that are
      rich in particulates that have been found to sorb several organic contaminants.
      An analytical method based on off-line solid-phase extraction (SPE) followed by
      liquid chromatography-mass spectrometry (LC-MS) analysis was developed for the
      detection and quantification of 31 ECs from surface water, wastewater, suspended
      particulate matter (SPM) as well as sediments. Lyophilized sediments and air
      dried SPM were subjected to ultrasonic extraction. Water samples and extracts
      were then concentrated and cleaned-up by off-line SPE. Quantification was
      realized using a Q Exactive mass spectrometer in both full scan (FS) and MS2
      modes. These two modes were optimized and compared to determine which one was the
      most suitable for each matrix studied. Yeast estrogen screen assay (YES-assay)
      adapted from the direct measurement of estrogenic activity without sample
      extraction was tested on filtered wastewater samples. An endocrine disrupting
      effect was detected in all effluent samples analyzed with estradiol equivalent
      concentrations ranging from 4.4 to 720 ng eq E2 L-1 for the WWTP-1 and 6.5-42 ng
      eq E2 L-1 for the WWTP-2. The analytical methods were also applied on six samples
      of surface water, the corresponding SPM, the sediments and thirty-nine effluent
      samples from two wastewater treatment plants (WWTPs) sampled over a period of
      five months (February to June 2014).

PMID- 27705829
TI  - Effects of organic acids of different molecular size on phosphate removal by HZO
      201 nanocomposite.
AB  - Various organic acids in wastewater effluent could significantly influence the
      performance of phosphate adsorbent. This study focused on the effects of organic
      acids of different-molecular-size on phosphate adsorption by a novel
      nanocomposite HZO-201. Three organic acids (gallic acid (GA), tannic acid (TA)
      and humic acid (HA)) with distinct molecular size (HA > TA > GA) were chosen for
      this purpose. Both isotherm and kinetic tests of phosphate adsorption were
      conducted in the single-phosphate and binary system, and a series of microscopic
      techniques (i.e., XPS, FT-IR and SEM-EDX) and N2 adsorption-desorption test were
      employed to explore the underlying mechanism. It was found that GA could greatly
      weaken phosphate adsorption capability of HZO-201 by directly competing for
      ammonium group on the nanocomposite, TA exhibited significant inhibition on
      phosphate adsorption rate mainly through pore constriction/blockage, while HA
      posed negligible impact on phosphate adsorption because of the size exclusion
      effect. It was also observed that although GA, TA and HA showed substantial
      influence on bulky HZO due to complexation, their impact on the nano-HZO loaded
      inside HZO-201 was little. The covalently bounded ammonium group and the
      networking pore structure of HZO-201 may play important roles in it.

PMID- 27705828
TI  - Occupational exposure to PCDDs, PCDFs, and DL-PCBs in metallurgical plants of the
      Brescia (Lombardy Region, northern Italy) area.
AB  - The concentration values of polychlorodibenzodioxins (PCDDs),
      polychlorodibenzofurans (PCDFs), and dioxin-like polychlorobiphenyls (DL-PCBs) in
      blood serum samples (pools) of metallurgical workers in the area of the city of
      Brescia (northern Italy) were statistically processed. As to workers' exposure
      characteristics, pools were divided into 34 professionally exposed (PE) and 11
      non-professionally exposed (NPE). A further subdivision of PE pools was according
      to workplaces in which ferrous (N = 24) and non-ferrous (N = 10) materials were
      handled. To evaluate the aforesaid differences we applied the age-adjusted
      Generalized Linear Models. We identified significant (P <= 0.05) exposure models
      of the classification groups. The first subdivision was confirmed by the
      concentrations of 1,2,3,4,6,7,8-H7CDF, DL-PCB 105, and DL-PCB 189; the second was
      confirmed by the concentrations of PCDF TEQ97, PCDD + PCDF + DL-PCB (TEQTOT)
      TEQ97, 2,3,4,7,8-P5CDF, 1,2,3,6,7,8-H6CDD, 1,2,3,4,6,7,8-H7CDD, and PCB 189.
      Based on the literature, all mentioned congeners have been found in stack gas and
      fly ash samples of metallurgical plants: therefore, these indicators indicate the
      exposure to such work environments. Specifically, the concentrations measured in
      the workers' blood serum appear to depend on the type of material processed
      during work.

PMID- 27705831
TI  - Predicting acute contact toxicity of pesticides in honeybees (Apis mellifera)
      through a k-nearest neighbor model.
AB  - Ecological risk assessment of plant protection products (PPPs) requires an
      understanding of both the toxicity and the extent of exposure to assess risks for
      a range of taxa of ecological importance including target and non-target species.
      Non-target species such as honey bees (Apis mellifera), solitary bees and bumble
      bees are of utmost importance because of their vital ecological services as
      pollinators of wild plants and crops. To improve risk assessment of PPPs in bee
      species, computational models predicting the acute and chronic toxicity of a
      range of PPPs and contaminants can play a major role in providing structural and
      physico-chemical properties for the prioritisation of compounds of concern and
      future risk assessments. Over the last three decades, scientific advisory bodies
      and the research community have developed toxicological databases and
      quantitative structure-activity relationship (QSAR) models that are proving
      invaluable to predict toxicity using historical data and reduce animal testing.
      This paper describes the development and validation of a k-Nearest Neighbor (k
      NN) model using in-house software for the prediction of acute contact toxicity of
      pesticides on honey bees. Acute contact toxicity data were collected from
      different sources for 256 pesticides, which were divided into training and test
      sets. The k-NN models were validated with good prediction, with an accuracy of
      70% for all compounds and of 65% for highly toxic compounds, suggesting that they
      might reliably predict the toxicity of structurally diverse pesticides and could
      be used to screen and prioritise new pesticides.

PMID- 27705830
TI  - Non-target analysis of household dust and laundry dryer lint using comprehensive
      two-dimensional liquid chromatography coupled with time-of-flight mass
      spectrometry.
AB  - Household dust and laundry dryer lint are important indoor environmental matrices
      that may have notable health effects on humans due to chronic exposure. However,
      due to the sample complexity the studies conducted on these sample matrices until
      now were almost exclusively on the basis of target analysis. In this study,
      comprehensive two-dimensional liquid chromatography coupled with time-of-flight
      mass spectrometry (LC * LC-ToF MS) was applied, to enable non-target analysis of
      household dust as well as laundry dryer lint for the first time. The higher peak
      capacity and good orthogonality of LC * LC, together with reduced ion suppression
      in the MS enabled rapid identification of environmental contaminants in these
      complex sample matrices. A number of environmental contaminants were tentatively
      identified based on their accurate masses and isotopic patterns, including
      plasticizers, flame retardants, pesticides, drug metabolites, etc. The identity
      of seven compounds: tris(2-butoxyethyl) phosphate, tris(2-chloropropyl)
      phosphate, n-benzyl butyl phthalate, dibutyl phthalate, tributyl phosphate,
      triethyl phosphate and N, N-diethyl-meta-toluamide was confirmed using two
      dimensional retention alignment and their concentrations in the samples were semi
      quantitatively determined.

PMID- 27705832
TI  - Physiological and biochemical effects of nickel on rainbow trout (Oncorhynchus
      mykiss) tissues: Assessment of nuclear factor kappa B activation, oxidative
      stress and histopathological changes.
AB  - We investigated changes in nuclear factor kappa B (NFkB) activity, antioxidant
      responses and histopathological effects in the liver, gill and kidney tissues of
      rainbow trout exposed to nickel chloride (Ni). Two different concentrations (1
      mg/L and 2 mg/L) were administrated to fish for 21 days. Tissues were taken from
      all fish for NFkB activity, histopathological examination and determination of
      superoxide dismutase (SOD), catalase (CAT) enzyme activity and of lipid
      peroxidation (LPO), and glutathione (GSH) levels. The findings of this study
      indicated that Ni exposure led to a significant increase in LPO indicating
      peroxidative damage and antioxidant enzymes SOD and CAT activity in tissues (p <
      0.05), but 2 mg/Ni concentration caused a significant decrease in CAT activity in
      kidney tissues (p < 0.05). One of mechanism in the antioxidant defense system
      seems to be GSH, which increased in gill and kidney tissues of fish exposed to Ni
      (p < 0.05). NFkB immunopositivity was detected in all tissues. Ni exposure caused
      lamellar thickening, cellular infiltration in gill tissues, hydropic degeneration
      of hepatocytes in liver tissues, hyalinous accumulation within the glomeruli and
      tubular degeneration in kidney tissues. Our results suggested that Ni toxicity
      may disturb the biochemical and physiological functions of fish by causing
      changes in NFkB activity and oxidative and histopathological damage in the
      tissues of rainbow trout. This study can provide useful information for
      understanding of Ni-induced toxicity.

PMID- 27705833
TI  - Chronic diclofenac exposure affects gill integrity and pituitary gene expression
      and displays estrogenic activity in nile tilapia (Oreochromis niloticus).
AB  - Oreochromis niloticus has been exposed to diclofenac (DCF), a nonsteroidal anti
      inflammatory drug prevalent in the aquatic environment, for 80 days post-hatch
      (dph). Concentrations ranged from environmentally relevant (0.1 MUg L-1 and 1 MUg
      L-1 DCF) up to 100-fold thereof. Population relevant endpoints (hatching,
      survival, growth) as well as gill histopathology were analyzed. On this level of
      examination only gills exhibited mild to moderate alterations. On the contrary,
      biomarkers associated with reproduction were affected due to DCF exposure,
      indicating the potential to affect sexual differentiation and gametogenesis by
      acting as an estrogenic endocrine disrupting compound (EDC) in tilapia.
      Vitellogenin (VTG) gene expression was significantly induced at 1 MUg L-1 DCF. In
      order to find an explanation, gene expression patterns of key enzymes of the
      biotransformation phases I, II, and III have been analyzed. It seems very likely
      that the detoxification metabolism is induced in a dose dependent manner at
      higher concentrations of DCF leading to the expression pattern of VTG mRNA. Our
      results suggest that DCF at environmentally relevant concentrations adversely
      affects O. niloticus gill histopathology and pituitary gene expression, and has
      the potential to act as an estrogenic EDC. The sensitivity of various endpoints,
      however, differs and therefore these endpoints should be linked.

PMID- 27705834
TI  - 1,3-Dinitrobenzene reductive degradation by alkaline ascorbic acid - Reaction
      mechanisms, degradation pathways and reagent optimization.
AB  - Nitro-aromatic compounds (NACs) such as 1,3-dinitrobenzene (1,3-DNB) contain the
      nitrogroup (-NO2), in which the N with a +III oxidation state accepts electrons.
      Water soluble ascorbic acid (AsA) at elevated pH produces electron transfer and
      governs the electron-donating pathway. The influence of the NaOH/AsA molar ratio
      on the degradation of 1,3-DNB was investigated. Using 0.21-2 M NaOH and 20-100 mM
      AsA, nearly complete 1,3-DNB removals (90-100%) were achieved within 0.5 h. On
      the basis of intermediates identified using GC/MS, the reduction pathways of 1,3
      DNB can be categorized into step-by-step electron transfer, and condensation
      routes. A higher NaOH/AsA molar ratio would result in relatively higher AsA
      decomposition, promote the condensation route into the formation of azo- and
      azoxy-compounds, and ultimately reduce 1,3-DNB to 1,3-phenylenediamine.
      Contaminated soil flushing using 500 mM NaOH/100 mM AsA revealed that 1,3-DNB was
      completely degraded within 2 h. Based on these test results, the alkaline AsA
      treatment method is a potential remediation process for NACs contaminated soils.

PMID- 27705835
TI  - Structural features of N-glycans linked to glycoproteins expressed in three kinds
      of water plants: Predominant occurrence of the plant complex type N-glycans
      bearing Lewis a epitope.
AB  - The Japanese cedar pollen allergen (Cry j1) and the mountain cedar pollen
      allergen (Jun a1) are glycosylated with plant complex type N-glycans bearing
      Lewis a epitope(s) (Galbeta1-3[Fucalpha1-4]GlcNAc-). The biological significance
      of Lewis a type plant N-glycans and their effects on the human immune system
      remain to be elucidated. Since a substantial amount of such plant specific N
      glycans are required to evaluate immunological activity, we have searched for
      good plant-glycan sources to characterize Lewis a epitope-containing plant N
      glycans. In this study, we have found that three water plants, Elodea nuttallii,
      Egeria densa, and Ceratophyllum demersum, produce glycoproteins bearing Lewis a
      units. Structural analysis of the N-glycans revealed that almost all
      glycoproteins expressed in these three water plants predominantly carry plant
      complex type N-glycans including the Lewis a type, suggesting that these water
      plants are good sources for preparation of Lewis a type plant N-glycans in
      substantial amounts.

PMID- 27705836
TI  - The risk factors for gestational diabetes mellitus: A retrospective study.
AB  - OBJECTIVE: To investigate the risk factors for developing GDM among Taiwanese
      pregnant women. DESIGN: A retrospective cohort and case-control study. SETTING:
      At a medical centre in Southern Taiwan. PARTICIPANTS: The hospitalised pregnant
      women who were diagnosed with either GDM or normal glucose tolerance (NGT)
      between 1997 and 2011. The glucose tolerance test results were interpreted
      according to criteria established by the National Diabetes Data Group for GDM.
      Participants were divided into either a GDM group (case group) or a normal
      glucose tolerance (NGT) group (control group) in order to determine the risk
      factors for GDM. MEASUREMENTS: With a retrospective chart review, data regarding
      demographics, a family history of diabetes, history of gestation, and
      physiological index for pre- and postpregnancy periods were collected. chi2 tests
      and independent t tests were used to examine the correlations between demographic
      characteristics and GDM. Stepwise multivariate logistic regression was used to
      determine the factors associated with GDM. FINDINGS: The results of the
      comparison between the GDM group (n=106) and the NGT group (n=406) showed that
      the risk factors for GDM were maternal age, education, a family history of
      diabetes, and prepregnancy body mass index (BMI). KEY CONCLUSION AND IMPLICATION
      FOR PRACTICE: Older age, lower levels of education, a family history of diabetes,
      and higher prepregnancy BMI were significant risk factors for GDM. In addition to
      performing risk factor assessment, health care providers should proactively
      promote the importance of GDM screening to pregnant women at their first
      antenatal visit.

PMID- 27705837
TI  - Perspectives on enhancing international practical training of students in health
      and social care study programs - A qualitative descriptive case study.
AB  - BACKGROUND: Internationalization of practical training in health and social care
      study programs is an important aspect of higher education. However, field
      mentors' and classroom teachers' competence in guiding culturally diverse
      students varies widely in European countries, and the majority does not have
      enough training in guiding foreign students. OBJECTIVES: This study aimed to
      examine which factors enhance the efficacy of international practical placement
      experiences in health and social care study programs. DESIGN: A qualitative
      descriptive case study design was used. SETTINGS: The study was conducted at six
      higher education institutions-two in Finland and one in Croatia, Estonia, the
      Netherlands and Slovenia. PARTICIPANTS: A convenience sample of 14 mentors, 15
      teachers and 14 students with international experiences from six higher education
      institutions which are part of the Bologna Process was recruited. METHODS: The
      data were collected from six focus groups using a semi-structured questionnaire
      based on a literature review. Each higher education institution conducted one
      group interview that was tape-recorded, transcribed and analysed for themes.
      RESULTS: Participants made several recommendations for enhancing the practical
      placement experience of students, teachers, and mentors. Most recommendations
      dealt with practical supervision of students. Three major themes noted were:
      'Attitudes towards internationalization of practical placements', 'Factors
      impacting the international placement experience', and 'Pedagogical methods used
      and structural support available for internationalization.' CONCLUSIONS: The
      study highlights the need for strengthening the multicultural knowledge and
      skills of mentors and teachers. The findings provide practical guidelines for
      improving the international placement experience across health and social care
      fields.

PMID- 27705838
TI  - Luteinizing hormone-follicle stimulating hormone ratio as biological predictor of
      post-partum depression.
AB  - BACKGROUND: Post-partum depression (PPD) is the common adverse outcome of child
      bearing which affects the wellbeing of both mother and newborn and has long-term
      effects. Hence, reliable potential biological tests for early detection of PPD
      are essential. Follicle stimulating hormone (FSH) and luteinizing hormone (LH)
      were associated with depressive disorders and the present study estimated the
      levels of serum FSH, LH in postpartum depression and explored them as predictive
      biomarkers in the development of PPD. METHODS: In this nested case control study
      done at a tertiary care hospital in South India, 450 postpartum women were
      screened at 6th week post-delivery for PPD. Socio-demographic and clinical data
      were recorded and depressive symptoms were assessed using Edinburgh Postnatal
      Depression Scale (EPDS). Out of 450 subjects screened, 100 women with depressive
      symptoms were categorized as cases and 100 controls were selected from the
      remaining subjects matching for age and BMI with cases. Serum levels of FSH and
      LH were measured using direct competitive immunoassay by chemiluminescene
      technology. RESULTS: Serum LH/FSH ratio was found to be significantly (p=0.02)
      low in PPD women when compared to normal postpartum subjects. We also found a
      significant negative correlation between LH/FSH ratio and EPDS scores. Based on
      the receiver operating characteristic curve, the optimal cut-off value for serum
      of LH/FSH levels in predicting postpartum depression was estimated to be
      0.22mlU/mL with an AUC of 0.598 (95%CI, 0.291-0.859). CONCLUSION: Our study
      demonstrated that low LH/FSH ratio after delivery was associated with increased
      risk for the development of PPD. Low LH/FSH ratio at six-week post delivery can
      be used as a robust biochemical predictor of post-partum depression.

PMID- 27705839
TI  - 30-year nationwide trends in incidence of atrial fibrillation in Denmark and
      associated 5-year risk of heart failure, stroke, and death.
AB  - BACKGROUND: Long-term nationwide trends in atrial fibrillation (AF) incidence and
      5-year outcomes are rare. METHODS: We conducted a population-based cohort study
      using the Danish National Patient Registry covering all Danish hospitals. We
      computed standardized incidence rates during 1983-2012. We used Cox regression to
      estimate hazard ratios (HRs) of heart failure, stroke, and death within 5years,
      comparing 5-year calendar periods with the earliest period (1983-1987) as
      reference. RESULTS: We identified 312,420 patients with first-time hospital
      diagnosed AF. The incidence rate per 100,000person-years increased from 98 in
      1983 to 307 in 2012. The mean annual increase during the 30-year study period was
      4%, with a 6% increase annually until 2000 and a 1.4% increase annually
      thereafter. The incidence trends were most pronounced among men and persons above
      70years. Among high-risk subgroups, AF incidence was consistently highest in
      patients with valvular heart disease or heart failure. The rate of heart failure
      following AF declined by 50% over the entire study period (HR: 0.49, 95%
      confidence interval (CI): 0.48-0.51) and the mortality rate declined by 40% (HR:
      0.62, 95% CI: 0.61-0.63). Within the last two decades, the rate for ischemic
      stroke declined by 20% (HR 0.81, 95% CI: 0.78-0.84), but increased almost as much
      for haemorrhagic stroke (HR: 1.14, 95% CI: 1.01-1.29). CONCLUSIONS: The long-term
      risk of heart failure, ischemic stroke, and death following onset of AF has
      decreased remarkably over the last three decades. Still, the threefold increased
      incidence of hospital-diagnosed AF during the same period is a major public
      health concern.

PMID- 27705840
TI  - What do patients value about spinal manipulation and home exercise for back
      related leg pain? A qualitative study within a controlled clinical trial.
AB  - BACKGROUND: Patient perceptions may influence the effectiveness and utilization
      of healthcare interventions, particularly for complex health conditions such as
      sciatica or back-related leg pain (BRLP). OBJECTIVES: To explore BRLP patients'
      perceptions of spinal manipulative therapy (SMT) and home exercise with advice
      (HEA). DESIGN: Qualitative study in a controlled clinical trial. METHOD: Semi
      structured interviews conducted after 12 weeks of treatment asked participants
      about satisfaction with care and whether treatment was worthwhile. An
      interdisciplinary research team conducted content analysis using qualitative data
      analysis software to identify and summarize themes. RESULTS: Of 192 trial
      participants, 174 (91%) completed interviews (66% female, age 57.0 +/- 11.5
      years). Participants identified interactions with providers and staff, perceived
      treatment effects, and information as key contributors to both their satisfaction
      and the worthwhile nature of treatment. HEA was liked for its convenience and
      ability to foster an exercise habit. SMT was liked for specific aspects of the
      modality (e.g. manipulation, stretching) and provider competency. Most
      participants reported no dislikes for SMT or HEA, but some noted the dose/time
      commitment for SMT and discipline of HEA as least liked aspects of the
      interventions. CONCLUSIONS: The quality of patient-provider interactions,
      perceived treatment effects, and information sharing influenced BRLP patients'
      satisfaction with care. Qualitative research describing patients' preferences can
      facilitate translation of study findings into practice and allow clinicians to
      tailor treatments to facilitate compliance and satisfaction with care.

PMID- 27705841
TI  - Human dihydrofolate reductase influences the sensitivity of the malaria parasite
      Plasmodium falciparum to ketotifen - A cautionary tale in screening transgenic
      parasites.
AB  - Ketotifen has recently been reported to inhibit the growth of both asexual and
      sexual malaria parasites. A parasite transporter, PfgABCG2, has been implicated
      in its mechanism of action. Human dihydrofolate reductase (hDHFR) is the most
      commonly used selectable marker to create transgenic Plasmodium falciparum cell
      lines. Growth assays using transgenic P. falciparum parasites with different
      selectable markers revealed that the presence of hDHFR rather than the absence of
      PfgABCG2 is responsible for a shift in the parasite's sensitivity to ketotifen.
      Employing a range of in vitro assays and liquid chromatography-mass spectrometry
      we show that ketotifen influences hDHFR activity, but it is not metabolised by
      the enzyme. Our data also highlights potential pitfalls when functionally
      characterising transgenic parasites.

PMID- 27705842
TI  - Beverage-specific patterns of 5+ alcoholic drink consumption by young adults in
      the U.S.
AB  - Young adult binge drinking prevalence has been widely researched. However,
      beverage-specific binge drinking rates for beer, liquor, wine, and wine coolers
      have not yet been documented for this age group. This study examines consumption
      of specific beverages (i.e., 5+ drinks in a row in the past two weeks) by young
      adults aged 19/20. Data from the national Monitoring the Future study were
      collected one or two years after high school from 2004 to 2014 (n=2004). Logistic
      regression was used to examine associations between beverage-specific 5+ drinking
      and gender, race/ethnicity, parent education, college status, and cohort year.
      Overall 5+ drinking in the past two weeks was reported by 31.4% of young adults.
      Beverage-specific 5+ drinking was most common with liquor (22.6%) and beer
      (22.4%), followed by wine (4.5%) and wine coolers (3.0%). Men were more likely
      than women to engage in 5+ drinking with beer and liquor; women were more likely
      than men to do so with wine and wine coolers. Beverage-specific patterns differed
      by college attendance. Compared to four-year college students, two-year
      college/votech students were less likely to have 5+ drinks of liquor or wine, and
      more likely to have 5+ wine coolers; those not in college were less likely to
      have 5+ drinks of liquor and more likely to have 5+ wine coolers. Differences in
      beverage-specific 5+ drinking by gender and college enrollment suggest that
      intervention efforts should focus on the beverages that are most commonly
      consumed at high levels within specific early young adult populations.

PMID- 27705843
TI  - Alcohol detoxification completion, acceptance of referral to substance abuse
      treatment, and entry into substance abuse treatment among Alaska Native people.
AB  - BACKGROUND: Little is known about factors associated with detoxification
      treatment completion and the transition to substance abuse treatment following
      detoxification among Alaska Native people. This study examined 3 critical points
      on the substance abuse continuum of care (alcohol detoxification completion,
      acceptance of referral to substance abuse treatment, entry into substance abuse
      treatment following detoxification). METHODS: The retrospective cohort included
      383 adult Alaska Native patients admitted to a tribally owned and managed
      inpatient detoxification unit. Three multiple logistic regression models
      estimated the adjusted associations of each outcome separately with
      demographic/psychosocial characteristics, clinical characteristics, use related
      behaviors, and health care utilization. RESULTS: Seventy-five percent completed
      detoxification treatment. Higher global assessment functioning scores, longer
      lengths of stay, and older ages of first alcohol use were associated with
      completing detoxification. A secondary drug diagnosis was associated with not
      completing detoxification. Thirty-six percent accepted a referral to substance
      abuse treatment following detoxification. Men, those with legal problems, and
      those with a longer length of stay were more likely to accept a referral to
      substance abuse treatment. Fifty-eight percent had a confirmed entry into a
      substance abuse treatment program at discharge. Length of stay was the only
      variable associated with substance abuse treatment entry. CONCLUSIONS: Services
      like motivational interviewing, counseling, development of therapeutic alliance,
      monetary incentives, and contingency management are effective in linking patients
      to services after detoxification. These should be considered, along with the
      factors associated with each point on the continuum of care when linking patients
      to follow-up services.

PMID- 27705844
TI  - Abdominal and pelvic manifestations of Rosai-Dorfman disease: a review of four
      cases.
AB  - Rosai-Dorfman disease is a rare disorder of unknown etiology caused by the
      proliferation of histiocytes within lymph nodes, predominantly in the cervical
      chain. Extranodal sites may be involved as well, with involvement of nearly every
      organ system described in the literature. Abdominal and pelvic manifestations of
      Rosai-Dorfman disease are extremely rare. We present four cases of abdominal and
      pelvic involvement by Rosai-Dorfman disease, specifically within the biliary
      tract, pancreas, spleen, and presacral space. Of note, a presacral mass was
      present in three of the four patients, and although not previously reported in
      Rosai-Dorfman disease, may suggest the diagnosis in the proper clinical scenario.

PMID- 27705845
TI  - Inactivation efficiency and mechanism of UV-TiO2 photocatalysis against murine
      norovirus using a solidified agar matrix.
AB  - Human norovirus (HuNoV) is the primary cause of viral gastroenteritis worldwide.
      Fresh blueberries are among high risk foods associated with norovirus related
      outbreaks. Therefore, it is important to assess intervention strategies to reduce
      the risk of foodborne illness. The disinfection efficiency of decontamination
      methods is difficult to evaluate for fruits and vegetables due to an inconsistent
      degree of contamination and irregular surface characteristics. The inactivation
      efficiency and mechanism of murine norovirus 1 (MNV-1, a surrogate for HuNoV) was
      studied on an experimentally prepared solidified agar matrix (SAM) to simulate
      blueberries using different wavelengths (A, B, C) of UV light both with and
      without TiO2 photocatalysis (TP). MNV-1 was inoculated on exterior and interior
      of SAM and inactivation efficiencies of different treatments were investigated
      using a number of assays. Initial inoculum levels of MNV-1 on the SAM surface and
      interior were 5.2logPFU/mL. UVC with TiO2 (UVC-TP) achieved the highest level of
      viral reduction for both externally inoculated and internalized MNV-1. Externally
      inoculated MNV-1 was reduced to non-detectable levels after UVC-TP treatment for
      5min while there was still a 0.9 log viral titer after UVC alone. For
      internalized MNV-1, 3.2 log and 2.7 log reductions were obtained with UVC-TP and
      UVC alone treatments for 10min, respectively. The Weibull model was applied to
      describe the inactivation behavior of MNV-1, and the model showed a good fit to
      the data. An excellent correlation between the steady-state concentration of OH
      radicals ([OH]ss) and viral inactivation was quantified using a para
      chlorobenzoic acid (pCBA) probe compound, suggesting that OH radicals produced in
      the UV-TP reaction were the major species for MNV-1 inactivation. Transmission
      electron microscopy images showed that the structure of viral particles was
      completely disrupted with UVC-TP and UVC alone. SDS-PAGE analysis showed that the
      major capsid protein VP1 was degraded after UVC-TP and UVC alone. Real-time RT
      qPCR analysis showed that UVC-TP and UVC alone caused a reduction in the level of
      viral genomic RNA. Propidium monoazide (PMA) pretreatment RT-qPCR analysis showed
      that UVC-TP caused damage to the viral capsid protein in addition to viral
      genomic RNA. UVC both with and without TiO2 was more effective for MNV-1
      inactivation than UVB and UVA. Thus, UVC-TP disinfection aimed to reduce levels
      of food-borne viruses can inactivate viruses present on the surface and
      internalized in the interior of blueberries.

PMID- 27705846
TI  - Investigation of the interaction between berberine and nucleosomes in solution:
      Spectroscopic and equilibrium dialysis approach.
AB  - Berberine is a natural plant alkaloid with high pharmacological potential.
      Although its interaction with free DNA has been the subject of several reports,
      to date there is no work concerning the effect of berberine on nucleoprotein
      structure of DNA, the nucleosomes. The present study focuses on the binding
      affinity of berberine to nucleosomes and histone H1 employing various
      spectroscopic techniques, fluorescence, circular dichroism, thermal denaturation
      as well as equilibrium dialysis. The results showed that the binding of berberine
      to nucleosomes is positive cooperative with Ka=5.57*103M-1. Berberine quenched
      with the chromophores of protein moiety of nucleosomes and reduced fluorescence
      emission intensity at 335nm with Ksv value of 0.135. Binding of berberine to
      nucleosomes decreased the absorbance at 210 and 260nm, produced hypochromicity in
      thermal denaturation profiles and its affinity to nucleoprotein structure of
      nucleosomes was much higher than to free DNA. Berberine also exhibited high
      affinity to histone H1 in solution and the binding was positive cooperative with.
      Ka=3.61*103M-1. Moreover berberine decreased fluorescence emission intensity of
      H1 by quenching with tyrosine residue in its globular core domain. The circular
      dichroism profiles demonstrated that the binding of drug induced secondary
      structural changes in both DNA stacking and histone H1. It is concluded that
      berberine is genotoxic drug, interacts with nucleosomes and in this process
      histone H1 is involved to exert its anticancer activity.

PMID- 27705847
TI  - Tuning the physical properties of organic sensitizers by replacing triphenylamine
      with new donors for dye sensitized solar cells - a theoretical approach.
AB  - New donor molecules with low ionization potential have been theoretically
      designed by replacing the benzene moieties in triphenylamine (TPA) with thiophene
      as well as furan. The designed new donors also exhibited planar structure, making
      an angle of 120 degrees  around the nitrogen atom that results in resonance
      effects through pi-bonds of aryl rings. New sensitizers have been theoretically
      studied using DFT and TD-DFT by adopting these designed donors. UV-Vis absorption
      spectra, light harvesting ability (LHE) and electron injection ability
      (DeltaGinject) of the designed sensitizers have been calculated by taking L0 as
      reference. Orbital overlapping between donor and acceptor facilitates intra
      molecular charge transfer, thereby increasing the interfacial electron injection
      from the sensitizer to the semiconductor nanoparticles. Our theoretical results
      demonstrate that sensitizers DTPA-AA and DFPA-AA have broader absorption and
      lower DeltaGinject respectively compare to L0, this opens a new way for designing
      sensitizers for dye sensitized solar cells (DSSCs). All the dyes designed were
      found to be good light harvesters.

PMID- 27705848
TI  - Slow-electron velocity-map imaging study of aniline via resonance-enhanced two
      photon ionization method.
AB  - Slow electron velocity-map imaging (SEVI) of aniline has been investigated via
      two-color resonant-enhanced two-photo (1+1') ionization (2C-R2PI) method. A
      number of vibrational frequencies in the first excited state of neutral (S1) and
      2B1 ground electronic state of cation (D0) have been accurately determined. In
      addition, photoelectron angular distributions (PADs) in the two-step transitions
      are presented and reveal a near threshold shape resonance in the ionization of
      aniline. The SEVI spectra taken via various S1 intermediate states provide the
      detailed vibrational structures of D0 state and directly deduce the accurate
      adiabatic ionization potential (IP) of 62,271+/-6cm-1. Ab initio calculations
      excellently reproduce the experimental IP value (Theo. 62,242cm-1). For most
      vibrational modes, good agreement between theoretical and experimental
      frequencies in the S0 and D0 states of aniline is obtained to aid us to clearly
      assign vibrational modes. Especially, the vibrational frequencies calculated at
      the CASSCF level are much better consistent with experimental data than that
      obtained using the TDDFT and CIS methods.

PMID- 27705849
TI  - Molecular and structural characterization of some violet phosphate pigments for
      their non-invasive identification in modern paintings.

PMID- 27705851
TI  - More Than Just Monkey Business: What the Primate Microbiome Might Say About the
      Human One.
AB  - The science of the microbiome is arguably one of the hottest topics in medicine,
      and rightfully so. A deeper understanding of the ecology of the flora in our
      bodies is providing revolutionary insight beyond the simple form and function of
      our major parts. This new frontier is dauntingly complex, and most studies focus
      on details, failing to place these microbial ecosystems within the larger context
      of evolutionary time and environment.

PMID- 27705850
TI  - Fate and mass balance of contaminants of emerging concern during wastewater
      treatment determined using the fractionated approach.
AB  - Contaminants of emerging concern (CECs) are often poorly removed from wastewater
      using conventional treatment technologies and there is limited understanding of
      their fate during treatment. Inappropriate sampling strategies lead to
      inaccuracies in estimating removals of CECs. In this study, we used the
      "fractionated approach" that accounts for the residence time distribution (RTD)
      in treatment units to investigate the fate of 26 target CECs in a municipal
      wastewater treatment plant (WWTP) that includes primary, secondary and tertiary
      treatment steps. Prior hydraulic calibration of each treatment unit was
      performed. Wastewater and sludge samples were collected at different locations
      along the treatment train and the concentrations of target CECs were measured by
      liquid chromatography mass spectrometry. The most substantial aqueous removal
      occurred during activated sludge treatment (up to 99%). Removals were <50% in the
      primary clarifier and tertiary rotating biological contactors (RBCs) and up to
      70% by sand filtration. Mass balance calculations demonstrated that
      (bio)degradation accounted for up to 50% of the removal in the primary clarifier
      and 100% in activated sludge. Removal by sorption to primary and secondary sludge
      was minimal for most CECs. Analysis of the selected metabolites demonstrated that
      negative removals obtained could be explained by transformations between the
      parent compound and their metabolites. This study contributes to the growing
      literature by applying the fractionated approach to calculate removal of
      different types of CECs across each wastewater treatment step. An additional
      level of understanding of the fate of CECs was provided by mass balance
      calculations in primary and secondary treatments.

PMID- 27705854
TI  - Accurate Lungs Segmentation on CT Chest Images by Adaptive Appearance-Guided
      Shape Modeling.
AB  - To accurately segment pathological and healthy lungs for reliable computer-aided
      disease diagnostics, a stack of chest CT scans is modeled as a sample of a
      spatially inhomogeneous joint 3D Markov-Gibbs random field (MGRF) of voxel-wise
      lung and chest CT image signals (intensities). The proposed learnable MGRF
      integrates two visual appearance sub-models with an adaptive lung shape submodel.
      The first-order appearance submodel accounts for both the original CT image and
      its Gaussian scale space (GSS) filtered version to specify local and global
      signal properties, respectively. Each empirical marginal probability distribution
      of signals is closely approximated with a linear combination of discrete
      Gaussians (LCDG), containing two positive dominant and multiple sign-alternate
      subordinate DGs. The approximation is separated into two LCDGs to describe
      individually the lungs and their background, i.e., all other chest tissues. The
      second-order appearance submodel quantifies conditional pairwise intensity
      dependencies in the nearest voxel 26-neighborhood in both the original and GSS
      filtered images. The shape submodel is built for a set of training data and is
      adapted during segmentation using both the lung and chest appearances. The
      accuracy of the proposed segmentation framework is quantitatively assessed using
      two public databases (ISBI VESSEL12 challenge and MICCAI LOLA11 challenge) and
      our own database with, respectively, 20, 55, and 30 CT images of various lung
      pathologies acquired with different scanners and protocols. Quantitative
      assessment of our framework in terms of Dice similarity coefficients, 95
      percentile bidirectional Hausdorff distances, and percentage volume differences
      confirms the high accuracy of our model on both our database (98.4+/-1.0%, 2.2+/
      1.0 mm, 0.42+/-0.10%) and the VESSEL12 database (99.0+/-0.5%, 2.1+/-1.6 mm,
      0.39+/-0.20%), respectively. Similarly, the accuracy of our approach is further
      verified via a blind evaluation by the organizers of the LOLA11 competition,
      where an average overlap of 98.0% with the expert's segmentation is yielded on
      all 55 subjects with our framework being ranked first among all the state-of-the
      art techniques compared.

PMID- 27705856
TI  - Combining Simulated and Experimental Data to Simulate Ultrasonic Array Data From
      Defects in Materials With High Structural Noise.
AB  - Ultrasonic nondestructive testing inspections using phased arrays are performed
      on a wide range of components and materials. All real inspections suffer, to
      varying extents, from coherent noise, including image artifacts and speckle
      caused by complex geometries and grain scatter, respectively. By its nature, this
      noise is not reduced by averaging; however, it degrades the signal-to-noise ratio
      of defects and ultimately limits their detectability. When evaluating the
      effectiveness of an inspection, a large pool of data from samples containing a
      range of different defects are important to estimate the probability of detection
      of defects and to help characterize them. For a given inspection, coherent noise
      is easy to measure experimentally but hard to model realistically. Conversely,
      the ultrasonic response of defects can be simulated relatively easily. This paper
      proposes a novel method of simulating realistic array data by combining noise
      free simulations of defect responses with coherent noise taken from experimental
      data. This removes the need for costly physical samples with known defects to be
      made and allows for large data sets to be created easily.

PMID- 27705855
TI  - Nonlinear Imaging of Microbubble Contrast Agent Using the Volterra Filter: In
      Vivo Results.
AB  - A nonlinear filtering approach to imaging the dynamics of microbubble ultrasound
      contrast agents (UCAs) in microvessels is presented. The approach is based on the
      adaptive third-order Volterra filter (TVF), which separates the linear,
      quadratic, and cubic components from beamformed pulse-echo ultrasound data. The
      TVF captures polynomial nonlinearities utilizing the full spectral components of
      the echo data and not from prespecified bands, e.g., second or third harmonics.
      This allows for imaging using broadband pulse transmission to preserve the axial
      resolution and the SNR. In this paper, we present the results from imaging the
      UCA activity in a 200- [Formula: see text] cellulose tube embedded in a tissue
      mimicking phantom using a linear array diagnostic probe. The contrast enhancement
      was quantified by computing the contrast-to-tissue ratio (CTR) for the different
      imaging components, i.e., B-mode, pulse inversion (PI), and the TVF components.
      The temporal mean and standard deviation of the CTR values were computed for all
      frames in a given data set. Quadratic and cubic images, referred to as QB-mode
      and CB-mode, produced higher mean CTR values than B-mode, which showed improved
      sensitivity. Compared with PI, they produced similar or higher mean CTR values
      with greater spatial specificity. We also report in vivo results from imaging UCA
      activity in an implanted LNCaP tumor with heterogeneous perfusion. The temporal
      means and standard deviations of the echogenicity were evaluated in small regions
      with different perfusion levels in the presence and absence of UCA. The in vivo
      measurements behaved consistently with the corresponding calculations obtained
      under microflow conditions in vitro. Specifically, the nonlinear VF components
      produced larger increases in the temporal mean and standard deviation values
      compared with B-mode in regions with low to relatively high perfusion. These
      results showed that polynomial filters such as the TVF can provide an important
      tool for imaging UCA activity in regions with heterogeneous perfusion as is the
      case in some tumors and ischemic tissues.

PMID- 27705857
TI  - A Comparison of the Performance of Different Multiline Transmit Setups for Fast
      Volumetric Cardiac Ultrasound.
AB  - It was previously demonstrated in 2-D echocardiography that a proper multiline
      transmit (MLT) implementation can be used to increase frame rate while preserving
      image quality. Initial findings for extending MLT to 3-D showed that it might
      address the low spatiotemporal resolution of current volumetric ultrasound
      systems. However, to date, it remains unclear how much transmit/receive
      parallelization would be possible using a 3-D MLT system. Therefore, the aim of
      this paper was to contrast different MLT setups for 3-D imaging by computer
      simulation in order to determine an optimal tradeoff between the amount of
      parallelization of an MLT system and the corresponding signal-to-noise ratio of
      the resulting images. Hereto, the image quality of several MLT setups was
      estimated by quantifying their crosstalk energy level. The results showed that
      for the tested setups, 4MLT broad beams and 9MLT narrow beams with Tukey ( alpha
      = 0.5 ) apodization in transmit and receive give the highest frame rate gain
      while maintaining an acceptable interbeam interference level. Moreover, although
      16MLT narrow beams with Tukey/Tukey ( alpha = 0.5 ) apodization did show more
      pronounced interbeam interference, its gain in frame rate might outweigh its
      predicted loss in image quality. As such both 9MLT and 16MLT narrow beams were
      tested experimentally. For both systems, four receive lines were reconstructed
      from each transmit beam. The contrast-to-noise ratio of these imaging strategies
      was quantified and compared with the image quality obtained with line-by-line
      scanning. Despite some expected loss in image quality, the resulting images of
      the parallelized systems were very competitive to the benchmark, while speeding
      up the acquisition process by a factor of 36 and 64, respectively.

PMID- 27705859
TI  - Web Video Event Recognition by Semantic Analysis From Ubiquitous Documents.
AB  - In recent years, the task of event recognition from videos has attracted
      increasing interest in multimedia area. While most of the existing research was
      mainly focused on exploring visual cues to handle relatively small-granular
      events, it is difficult to directly analyze video content without any prior
      knowledge. Therefore, synthesizing both the visual and semantic analysis is a
      natural way for video event understanding. In this paper, we study the problem of
      Web video event recognition, where Web videos often describe large-granular
      events and carry limited textual information. Key challenges include how to
      accurately represent event semantics from incomplete textual information and how
      to effectively explore the correlation between visual and textual cues for video
      event understanding. We propose a novel framework to perform complex event
      recognition from Web videos. In order to compensate the insufficient expressive
      power of visual cues, we construct an event knowledge base by deeply mining
      semantic information from ubiquitous Web documents. This event knowledge base is
      capable of describing each event with comprehensive semantics. By utilizing this
      base, the textual cues for a video can be significantly enriched. Furthermore, we
      introduce a two-view adaptive regression model, which explores the intrinsic
      correlation between the visual and textual cues of the videos to learn reliable
      classifiers. Extensive experiments on two real-world video data sets show the
      effectiveness of our proposed framework and prove that the event knowledge base
      indeed helps improve the performance of Web video event recognition.

PMID- 27705860
TI  - Queuing Network Modeling of Driver EEG Signals-Based Steering Control.
AB  - Directly using brain signals rather than limbs to steer a vehicle may not only
      help disabled people to control an assistive vehicle, but also provide a
      complementary means of control for a wider driving community. In this paper, to
      simulate and predict driver performance in steering a vehicle with brain signals,
      we propose a driver brain-controlled steering model by combining an extended
      queuing network-based driver model with a brain-computer interface (BCI)
      performance model. Experimental results suggest that the proposed driver brain
      controlled steering model has performance close to that of real drivers with good
      performance in brain-controlled driving. The brain-controlled steering model has
      potential values in helping develop a brain-controlled assistive vehicle.
      Furthermore, this study provides some insights into the simulation and prediction
      of the performance of using BCI systems to control other external devices (e.g.,
      mobile robots).

PMID- 27705861
TI  - Conjugation of Bovine Serum Albumin With ZnO Nanosphere-A Novel Approach for
      Ultra-Low Level Mercury Ion Detection.
AB  - Solution-processed bovine serum albumin conjugated with ZnO nanosphere (BCZ) have
      been synthesized for ultra-low level mercury ion detection. Simple drop casting
      technique was adopted to fabricate such a mercury ion (Hg2+) detection scheme.
      Morphological and optical characterization of the BCZ was performed by
      Transmission Electron Microscopy (TEM), UV-Vis and Fluorescence spectroscopic
      technique prior to device fabrication. The working principle of the BCZ device
      for Hg2+ detection depends upon the variation of conductance with various
      concentration of Hg2+. An extensive study was carried out to investigate the
      effect of Hg2+ upon transport properties of BCZ. The ultra-low level of Hg2+
      sensing was performed using this electrical detection technique. More
      importantly, this proposed BCZ based detection technique is found to be simple,
      inexpensive and very fast in responding (response time  ~ 2.5 s) to heavy metal
      ion with a limit of detection (LOD) 0.03 fg/ml (S/ [Formula: see text]3).

PMID- 27705864
TI  - Delay-Dependent Global Exponential Stability for Delayed Recurrent Neural
      Networks.
AB  - This paper deals with the global exponential stability for delayed recurrent
      neural networks (DRNNs). By constructing an augmented Lyapunov-Krasovskii
      functional and adopting the reciprocally convex combination approach and
      Wirtinger-based integral inequality, delay-dependent global exponential stability
      criteria are derived in terms of linear matrix inequalities. Meanwhile, a general
      and effective method on global exponential stability analysis for DRNNs is given
      through a lemma, where the exponential convergence rate can be estimated. With
      this lemma, some global asymptotic stability criteria of DRNNs acquired in
      previous studies can be generalized to global exponential stability ones.
      Finally, a frequently utilized numerical example is carried out to illustrate the
      effectiveness and merits of the proposed theoretical results.

PMID- 27705863
TI  - An Integrated Approach to Characterize the Behavior of a Human Fingertip in
      Contact with a Silica Window.
AB  - Understanding the mechanisms of human tactual perception represents a challenging
      task in haptics and humanoid robotics. A classic approach to tackle this issue is
      to accurately and exhaustively characterize the mechanical behavior of human
      fingertip. The output of this characterization can then be exploited to drive the
      design of numerical models, which can be used to investigate in depth the
      mechanisms of human sensing. In this work, we present a novel integrated
      measurement technique and experimental set up for in vivo characterization of the
      deformation of the human fingertip at contact, in terms of contact area, force,
      deformation, and pressure distribution. The device presented here compresses the
      participant's fingertip against a flat surface, while the aforementioned
      measurements are acquired and experimental parameters such as velocity, finger
      orientation, and displacement (indentation) controlled. Experimental outcomes are
      then compared and integrated with the output of a 3D finite element (FE) model of
      the human fingertip, built upon existing validated models. The agreement between
      numerical and experimental data represents a validation for our approach.

PMID- 27705868
TI  - The Twist Tensor Nuclear Norm for Video Completion.
AB  - In this paper, we propose a new low-rank tensor model based on the circulant
      algebra, namely, twist tensor nuclear norm (t-TNN). The twist tensor denotes a
      three-way tensor representation to laterally store 2-D data slices in order. On
      one hand, t-TNN convexly relaxes the tensor multirank of the twist tensor in the
      Fourier domain, which allows an efficient computation using fast Fourier
      transform. On the other, t-TNN is equal to the nuclear norm of block circulant
      matricization of the twist tensor in the original domain, which extends the
      traditional matrix nuclear norm in a block circulant way. We test the t-TNN model
      on a video completion application that aims to fill missing values and the
      experiment results validate its effectiveness, especially when dealing with video
      recorded by a nonstationary panning camera. The block circulant matricization of
      the twist tensor can be transformed into a circulant block representation with
      nuclear norm invariance. This representation, after transformation, exploits the
      horizontal translation relationship between the frames in a video, and endows the
      t-TNN model with a more powerful ability to reconstruct panning videos than the
      existing state-of-the-art low-rank models.

PMID- 27705872
TI  - Multisensor-Based Periodic Estimation in Sensor Networks With Transmission
      Constraint and Periodic Mixed Storage.
AB  - In this paper, we consider a periodic estimation problem in sensor networks with
      a shared communication channel. The transmission constraint is inevitable in a
      single-channel-based sensor network if the sensors are heterogeneous or deployed
      far away from each other. A novel stochastic competitive transmission strategy is
      presented to deal with the transmission constraint, such that the sensors
      communicate with the fusion center (FC) in a strict asynchronous manner. A
      periodic mixed storage strategy combing the zero-input and the hold-input
      mechanisms is presented to describe periodic updating of the stored information
      in the sensors' buffers. A recursive Kalman filtering algorithm is derived for
      the FC to periodically generate estimates of state variables describing an object
      by using a linear continuous-time stochastic model. Two simulation examples are
      presented to show the effectiveness of the proposed results.

PMID- 27705873
TI  - Spectral Contextual Classification of Hyperspectral Imagery With Probabilistic
      Relaxation Labeling.
AB  - In this paper, a spectral-spatial classification framework based on probabilistic
      relaxation labeling using compatibility coefficients is proposed for
      hyperspectral images. It is a two-stage classifier that uses maximum a posteriori
      (MAP) estimation to maximize posterior probabilities of classification map
      obtained in first stage to incorporate spatial information for better
      classification accuracy. Two different forms of compatibility coefficients based
      on correlation and mutual information are used for MAP estimation. The initial
      probability estimates are obtained from probabilistic support vector machine
      (SVM) classifier. The combination of SVM with MAP estimation is investigated and
      compared with benchmark Markov random field and extended morphological profile
      based approaches and some other recent methods. The experimental results are
      presented for three airborne hyperspectral images. The results reveal that
      incorporation of contextual information with both forms of compatibility
      coefficients statistically significantly improved SVM results. The compatibility
      coefficients based on correlation produced the best results among the relaxation
      methods outperforming many existing methods.

PMID- 27705875
TI  - Robust Learning Control Design for Quantum Unitary Transformations.
AB  - Robust control design for quantum unitary transformations has been recognized as
      a fundamental and challenging task in the development of quantum information
      processing due to unavoidable decoherence or operational errors in the
      experimental implementation of quantum operations. In this paper, we extend the
      systematic methodology of sampling-based learning control (SLC) approach with a
      gradient flow algorithm for the design of robust quantum unitary transformations.
      The SLC approach first uses a "training" process to find an optimal control
      strategy robust against certain ranges of uncertainties. Then a number of
      randomly selected samples are tested and the performance is evaluated according
      to their average fidelity. The approach is applied to three typical examples of
      robust quantum transformation problems including robust quantum transformations
      in a three-level quantum system, in a superconducting quantum circuit, and in a
      spin chain system. Numerical results demonstrate the effectiveness of the SLC
      approach and show its potential applications in various implementation of quantum
      unitary transformations.

PMID- 27705876
TI  - A Neurodynamic Model to Solve Nonlinear Pseudo-Monotone Projection Equation and
      Its Applications.
AB  - In this paper, a neurodynamic model is given to solve nonlinear pseudo-monotone
      projection equation. Under pseudo-monotonicity condition and Lipschitz continuous
      condition, the projection neurodynamic model is proved to be stable in the sense
      of Lyapunov, globally convergent, globally asymptotically stable, and globally
      exponentially stable. Also, we show that, our new neurodynamic model is effective
      to solve the nonconvex optimization problems. Moreover, since monotonicity is a
      special case of pseudo-monotonicity and also since a co-coercive mapping is
      Lipschitz continuous and monotone, and a strongly pseudo-monotone mapping is
      pseudo-monotone, the neurodynamic model can be applied to solve a broader classes
      of constrained optimization problems related to variational inequalities, pseudo
      convex optimization problem, linear and nonlinear complementarity problems, and
      linear and convex quadratic programming problems. Finally, several illustrative
      examples are stated to demonstrate the effectiveness and efficiency of our new
      neurodynamic model.

PMID- 27705877
TI  - Single-Image Distance Measurement by a Smart Mobile Device.
AB  - Existing distance measurement methods either require multiple images and special
      photographing poses or only measure the height with a special view configuration.
      We propose a novel image-based method that can measure various types of distance
      from single image captured by a smart mobile device. The embedded accelerometer
      is used to determine the view orientation of the device. Consequently, pixels can
      be back-projected to the ground, thanks to the efficient calibration method using
      two known distances. Then the distance in pixel is transformed to a real distance
      in centimeter with a linear model parameterized by the magnification ratio.
      Various types of distance specified in the image can be computed accordingly.
      Experimental results demonstrate the effectiveness of the proposed method.

PMID- 27705878
TI  - Cardiac calcified amorphous tumors: CT and MRI findings.
AB  - PURPOSE: We aimed to evaluate computed tomography (CT) and magnetic resonance
      imaging (MRI) findings of cardiac calcified amorphous tumors (CATs). METHODS: CT
      and MRI findings of cardiac CATs in 12 patients were included. We retrospectively
      examined patient demographics, location, size, shape configuration, imaging
      features, calcification distribution of tumors, and accompanying medical
      problems. RESULTS: There was a female predominance (75%), with a mean age at
      presentation of 65 years. Patients were mostly asymptomatic on presentation
      (58.3%). The left ventricle of the heart was mostly involved (91%). CT findings
      of CATs were classified as partial calcification with a hypodense mass in four
      patients or a diffuse calcified form in eight. Calcification was predominant with
      large foci appearance as in partially calcified masses. On T1- and T2-weighted
      magnetic resonance images, CATs appeared hypointense and showed no contrast
      enhancement. CONCLUSION: The shape and configuration of cardiac CATs are variable
      with a narrow spectrum of CT and MRI findings, but large foci in a partially
      calcified mass or diffuse calcification of a mass on CT is very important in the
      diagnosis of cardiac CATs. Masses show a low signal intensity on T1- and T2
      weighted images with no contrast enhancement on MRI.

PMID- 27705879
TI  - Local tumor progression patterns after radiofrequency ablation of colorectal
      cancer liver metastases.
AB  - PURPOSE: We aimed to evaluate patterns of local tumor progression (LTP) after
      radiofrequency ablation (RF ablation) of colorectal cancer liver metastases
      (CRCLM) and to highlight the percentage of LTP not attributable to lesion size or
      RF ablation procedure-related factors (heat sink or insufficient ablation
      margin). METHODS: CRCLM treated by RF ablation at a single tertiary care center
      from 2004-2012, with a minimum of six months of postprocedure follow-up, were
      included in this retrospective study. LTP morphology was classified as focal
      nodular (<90 degrees  of ablation margin), circumferential (>270 degrees ), or
      crescentic (90 degrees -270 degrees ). Initial metastasis size, minimum ablation
      margin size, morphology of LTP, presence of a heat sink, and time to progression
      were recorded independently by two radiologists. RESULTS: Thirty-two of 127 RF
      ablation treated metastases (25%) with a mean size of 23 mm (standard deviation
      12 mm) exhibited LTP. Fifteen of 32 LTPs (47%) were classified as focal nodular,
      with seven having no procedure-related factor to explain recurrence. Ten of 32
      LTPs (31%) were circumferential, with four having no procedure-related factor to
      explain recurrence. Seven of 32 LTPs (22%) were crescentic, with two having no
      procedure-related factor to explain recurrence. Of the 13 lesions without any
      obvious procedure-related reason for LTP, six (46%) were <3 cm in size.
      CONCLUSION: Although LTP in RF ablation treated CRCLM can often be explained by
      procedure-related factors or size of the lesion, in this study up to six (5%) of
      the CRCLM we treated showed LTP without any reasonable cause.

PMID- 27705881
TI  - Decomposition analysis of the waste generation and management in 30 European
      countries.
AB  - An often suggested method for waste prevention is substitution of currently-used
      materials with materials which are less bulky, contain less hazardous components
      or are easier to recycle. For policy makers it is important to have tools
      available that provide information on the impact of this substitution on the
      changes in total amounts of waste generated and managed. The purpose of this
      paper is to see how much changes in the mix of 15 waste streams generated in
      eight economic sectors from 30 European countries have influenced the amounts of
      waste generated and managed in the period 2004-2012. In order to determine these
      impacts, two variations of the logarithmic mean Divisia index (LMDI) analysis
      model were developed and applied. The results show that the changes in the mix of
      waste streams in most cases did not have a considerable influence on the changes
      in the amounts of generated waste. In the analyses of waste sent for landfill,
      incineration without energy recovery, incineration with energy recovery and
      recovery other than energy recovery, the results also show that the changes in
      the mix of waste streams in most cases did not have the expected/desired
      influence on the changes in the amounts of managed waste. This paper provides an
      example on the possibilities of applying the LMDI analysis as a tool for
      quantifying the potential of effects which implemented or planned measures could
      have on the changes in waste management systems.

PMID- 27705880
TI  - Radiologic findings of screen-detected cancers in an organized population-based
      screening mammography program in Turkey.
AB  - PURPOSE: Bahcesehir Breast Cancer Screening Program is a population based
      organized screening program in Turkey, where asymptomatic women aged 40-69 years
      are screened biannually. In this prospective study, we aimed to determine the
      mammographic findings of screen-detected cancers and discuss the efficacy of
      breast cancer screening in a developing country. METHODS: A total of 6912 women
      were screened in three rounds. The radiologic findings were grouped as mass,
      focal asymmetry, calcification, and architectural distortion. Masses were
      classified according to shape, border, and density. Calcifications were grouped
      according to morphology and distribution. Cancers were grouped according to the
      clinical stage. RESULTS: Seventy cancers were detected with an incidence of
      4.8/1000. Two cancers were detected in other centers and three were not
      visualized mammographically. Mammographic presentations of the remaining 65
      cancers were mass (47.7%, n=31), calcification (30.8%, n=20), focal asymmetry
      (16.9%, n=11), architectural distortion (3.1%, n=2), and skin thickening (1.5%,
      n=1). The numbers of stage 0, 1, 2, 3, and 4 cancers were 13 (20.0%), 34 (52.3%),
      14 (21.5%), 3 (4.6%), and 1 (1.5%), respectively. The numbers of interval and
      missed cancers were 5 (7.4%) and 7 (10.3%), respectively. CONCLUSION: A high
      incidence of early breast cancer has been detected. The incidence of missed and
      interval cancers did not show major differences from western screening trials. We
      believe that this study will pioneer implementation of efficient population-based
      mammographic screenings in developing countries.

PMID- 27705882
TI  - The influence of residents' behaviour on waste electrical and electronic
      equipment collection effectiveness.
AB  - Government agencies have implemented regulations to reduce the volume of waste
      electrical and electronic equipment to protect the environment and encourage
      recycling. The effectiveness of systems through which waste electrical and
      electronic equipment is collected and recycled depends on (a) the development and
      operation of new programmes to process this material and (b) on information
      dissemination programmes aimed at manufacturers, retail sellers, and the
      consuming public. This study analyses these two elements. The main focus is to
      better understand household residents' behaviour in regards to the proper methods
      of handling waste electrical and electronic equipment and possible storage of the
      obsolete equipment that brings disturbances with collection of the waste
      equipment. The study explores these issues depending on size of municipality and
      the household residents' knowledge about legal methods of post-consumer
      management of waste electrical and electronic equipment in Poland, where the
      collection rate of that type of waste is about 40% of the total mass of waste
      electrical and electronic equipment appearing in the market.The research was
      informed by various sources of information, including non-government
      organisations, Inspectorate of Environmental Protection and Central Statistics
      Office in Poland, questionnaires, and interviews with the household residents.
      The questionnaires were distributed to daytime and vocational students from
      different universities and the customers of an electronic equipment superstore.
      The results show that a resident's behaviour in regards to the handling of
      obsolete waste electrical and electronic equipment can significantly reduce the
      collection rate, especially when the waste is discarded improperly - mixed with
      municipal waste or sold in scrapyards. It is possible to identify points that are
      necessary to be improved to achieve a higher collection rate.

PMID- 27705883
TI  - Effective plots to assess bias and precision in method comparison studies.
AB  - Bland and Altman's limits of agreement have traditionally been used in clinical
      research to assess the agreement between different methods of measurement for
      quantitative variables. However, when the variances of the measurement errors of
      the two methods are different, Bland and Altman's plot may be misleading; there
      are settings where the regression line shows an upward or a downward trend but
      there is no bias or a zero slope and there is a bias. Therefore, the goal of this
      paper is to clearly illustrate why and when does a bias arise, particularly when
      heteroscedastic measurement errors are expected, and propose two new plots, the
      "bias plot" and the "precision plot," to help the investigator visually and
      clinically appraise the performance of the new method. These plots do not have
      the above-mentioned defect and still are easy to interpret, in the spirit of
      Bland and Altman's limits of agreement. To achieve this goal, we rely on the
      modeling framework recently developed by Nawarathna and Choudhary, which allows
      the measurement errors to be heteroscedastic and depend on the underlying latent
      trait. Their estimation procedure, however, is complex and rather daunting to
      implement. We have, therefore, developed a new estimation procedure, which is
      much simpler to implement and, yet, performs very well, as illustrated by our
      simulations. The methodology requires several measurements with the reference
      standard and possibly only one with the new method for each individual.

PMID- 27705885
TI  - The preanalytical stability of glucagon as measured by liquid chromatography
      tandem mass spectrometry and two commercially available immunoassays.
AB  - Background One of the main challenges in the measurement of glucagon is the
      premise that it is unstable in human plasma. Traditionally, protease inhibitors
      have been used to prevent its degradation; however, their use is controversial.
      Here, we investigated the optimal method of sample collection for glucagon, with
      measurement by liquid chromatography tandem mass spectrometry (LC-MS/MS) and two
      commercially available immunoassays. Methods Blood from healthy fasting
      volunteers (n = 10) was processed under a variety of preanalytical conditions
      including collection in EDTA vs. lithium heparin tubes and the addition of
      aprotinin and/or a dipeptidyl-peptidase IV (DPPIV) inhibitor. Additionally, the
      effect of freeze thaw was assessed. Plasma glucagon concentrations were measured
      by LC-MS/MS and two commercially available immunoassays (HTRF(r) sandwich
      immunoassay, Cisbio and Milliplex MAP Human Metabolic Hormone Panel, Merck
      Millipore). Results A systematic bias of Milliplex > LC-MS/MS > HTRF was noted
      and plasma glucagon concentrations were significantly different between methods
      (Milliplex vs. LC-MS/MS P < 0.01; Milliplex vs. HTRF P < 0.0001; LC-MS/MS vs.
      HTRF P < 0.001). The addition of aprotinin, DPPIV inhibitor or a combination of
      aprotinin and DPPIV inhibitor had no effect on plasma glucagon concentrations
      when compared to 'non-stabilized' samples or each other. Whether samples were
      taken in EDTA tubes or lithium heparin tubes made no difference to plasma
      glucagon concentrations. These findings were consistent for all three methods.
      Plasma glucagon concentrations were not significantly different after two freeze
      thaw cycles (performed on samples in EDTA tubes containing aprotinin and DPPIV
      inhibitor). Conclusions This study demonstrates that glucagon is stable in both
      EDTA and lithium heparin tubes when stored at -80C. Furthermore, the addition of
      aprotinin and DPPIV inhibitors is unnecessary.

PMID- 27705884
TI  - Unified approach for extrapolation and bridging of adult information in early
      phase dose-finding paediatric studies.
AB  - The number of trials conducted and the number of patients per trial are typically
      small in paediatric clinical studies. This is due to ethical constraints and the
      complexity of the medical process for treating children. While incorporating
      prior knowledge from adults may be extremely valuable, this must be done
      carefully. In this paper, we propose a unified method for designing and analysing
      dose-finding trials in paediatrics, while bridging information from adults. The
      dose-range is calculated under three extrapolation options, linear, allometry and
      maturation adjustment, using adult pharmacokinetic data. To do this, it is
      assumed that target exposures are the same in both populations. The working model
      and prior distribution parameters of the dose-toxicity and dose-efficacy
      relationships are obtained using early-phase adult toxicity and efficacy data at
      several dose levels. Priors are integrated into the dose-finding process through
      Bayesian model selection or adaptive priors. This calibrates the model to adjust
      for misspecification, if the adult and pediatric data are very different. We
      performed a simulation study which indicates that incorporating prior adult
      information in this way may improve dose selection in children.

PMID- 27705886
TI  - Alcohol consumption reduces HbA1c and glycated albumin concentrations but not 1,5
      anhydroglucitol.
AB  - Background The effect of alcohol consumption on glycaemic control indicators is
      not well known. In this study, we studied the effect of alcohol consumption on
      the plasma glucose and glycaemic control indicators in non-diabetic men. Methods
      The study enrolled 300 non-diabetic men who received a complete medical checkup
      (age: 52.8 +/- 6.5 years, body mass index: 24.4 +/- 2.8 kg/m2). The subjects were
      divided into four groups by the amount of alcohol consumed, and the plasma
      glucose, HbA1c, glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG)
      concentrations of the groups were compared. Results As the level of alcohol
      consumption increased, significantly high concentrations of fasting plasma
      glucose (FPG) were observed, and the oral glucose tolerance test 2-h plasma
      glucose concentrations tended to rise. While no significant effect of alcohol
      consumption on HbA1c, 1,5-AG, and the 1,5-AG/FPG ratio was observed, the
      HbA1c/FPG ratio, GA and the GA/FPG ratio exhibited significantly low values as
      the level of alcohol consumption increased. In stepwise multivariate regression
      analysis, alcohol consumption was a significant negative independent variable for
      HbA1c and GA, but not for 1,5-AG. Conclusions As the level of alcohol consumption
      increased, the plasma glucose concentrations rose, but the HbA1c and GA
      concentrations were lower compared with the plasma glucose concentrations. These
      findings suggest that alcohol consumption may reduce HbA1c and GA concentrations,
      but not 1,5-AG.

PMID- 27705887
TI  - Chitotriosidase enzyme activity: is this a possible chronic inflammation marker
      in children with common variable immunodeficiency and early atherosclerosis?
AB  - Background Common variable immunodeficiency is a rare clinically symptomatic
      primary immunodeficiency disorder which manifests a wide variability of symptoms,
      complications. Atherosclerosis in common variable immunodeficiency patients has
      not been investigated yet contrary to other severe clinical complications. We
      aimed to investigate the chitotriosidase enzyme's role as an inflammation and
      atherosclerosis marker in paediatric common variable immunodeficiency patients.
      Methods Common variable immunodeficiency patients (n = 24) and healthy controls
      (n = 23) evaluated for chitotriosidase activity with other inflammation markers
      (hsCRP, myeloperoxidase, serum amyloid A, ferritin), lipid profile and
      echocardiographic findings (carotid artery intima media thickness - cIMT,
      brachial artery flow-mediated vazodilatation - FMD%). Results In patients, the
      mean chitotriosidase activity (8.98 +/- 6.28) was significantly higher than the
      controls (5.17 +/- 3.42) ( P = 0.014). Chitotriosidase showed positive relation
      with hs-CRP ( P = 0.011) and SAA ( P = 0.011) but had no relation with ferritin (
      P = 0.155), HDL ( P = 0.152) or LDL-cholesterol ( P = 0.380). Mean cIMT increased
      in patients compared with the controls ( P < 0.001) but did not show any relation
      with chitotriosidase ( P = 0.546). FMD% decreased in patients ( P < 0.001) also
      showing no relation with chitotriosidase ( P = 0.298). Ventricular myocardial
      performance indexes had no significant difference, but RVEF% decreased in
      patients ( P = 0.043). Conclusions High chitotriosidase activity in common
      variable immunodeficiency patients demonstrated in vivo the presence of activated
      macrophages indicating ongoing inflammation. Echocardiographic diastolic
      functional deficiency, increased cIMT and decreased FMD% may be accepted as early
      atherosclerotic findings, but none of them showed relationship with
      chitotriosidase activities.

PMID- 27705889
TI  - Impact of Proximal Cap Ambiguity on Outcomes of Chronic Total Occlusion
      Percutaneous Coronary Intervention: Insights From a Multicenter US Registry.
AB  - OBJECTIVES: We sought to determine the impact of proximal cap ambiguity on
      procedural techniques and outcomes for coronary chronic total occlusion (CTO)
      percutaneous coronary intervention (PCI). METHODS: We examined the clinical and
      angiographic characteristics and outcomes of 1021 CTO-PCIs performed between 2012
      and 2015 at 11 United States centers. RESULTS: Proximal cap ambiguity was present
      in 31% of target lesions and was associated with increased clinical and
      angiographic complexity (prior coronary artery bypass graft surgery: 43% vs 33%;
      P=.01; moderate/severe calcification 66% vs 51%; P<.001) and lower technical
      success (85% vs 93%; P<.001) and procedural success (84% vs 91%; P=.01), but
      similar incidence of major adverse cardiac events (3.2% vs 2.9%; P=.77). A
      retrograde approach was more commonly utilized among cases with proximal cap
      ambiguity (68% vs 33%; P<.001), and was more likely to be the initial (39% vs
      13%; P<.001) and successful approach (42% vs 20%; P<.001). Proximal cap ambiguity
      was associated with increased use of intravascular ultrasound (49% vs 36%; P=.01)
      and contrast (281 mL vs 250 mL; P<.001), higher air kerma radiation dose (4.0 Gy
      vs 3.0 Gy; P<.001), and longer procedure time (161 min vs 119 min; P<.001).
      CONCLUSIONS: Proximal cap ambiguity is present in one-third of CTO-PCI target
      lesions and is associated with lower success rates, higher utilization of the
      retrograde approach, and lower procedural efficiency, but no significant
      difference in the incidence of major adverse cardiac events.

PMID- 27705890
TI  - Influence of Human Immunodeficiency Virus Seropositive Status on the In-Hospital
      Management and Outcomes of Patients Presenting With Acute Myocardial Infarction.
AB  - OBJECTIVES: Human immunodeficiency virus (HIV) seropositive individuals are
      predisposed to acute myocardial infarction (AMI). We sought to evaluate
      management strategies and outcomes of AMI in patients with HIV in the
      contemporary era. METHODS: We analyzed data from the National Inpatient Sample
      from 2002 to 2011 for patients admitted with AMI with or without HIV. Propensity
      score matching was used to identify HIV seropositive AMI patients with similar
      characteristics who were managed invasively (cardiac catheterization,
      percutaneous coronary intervention [PCI], or coronary artery bypass graft surgery
      [CABG]) or conservatively. The primary outcome was in-hospital all-cause
      mortality. RESULTS: Among 1,363,570 patients admitted with AMI, 3788 (0.28%) were
      HIV seropositive. The frequency of HIV diagnosis among AMI patients increased
      over time (0.20% in 2002 to 0.35% in 2011; P for trend <.001). Patients with HIV
      had lower odds of invasive management (adjusted odds ratio [OR], 0.59; 95%
      confidence interval [CI], 0.55-0.65) and were less likely to undergo CABG (OR,
      0.66; 95% CI, 0.57-0.76) or receive drug-eluting stents (OR, 0.83; 95% CI, 0.76
      0.92) than HIV-seronegative patients. Patients with HIV had higher in-hospital
      mortality (adjusted OR, 1.36; 95% CI, 1.13-1.64) than those without HIV. In a
      propensity-matched cohort of 1608 patients with HIV treated for AMI with invasive
      vs conservative management, invasive management was associated with lower in
      hospital mortality (3.0% vs 8.2%; P<.001; OR, 0.34; 95% CI, 0.21-0.56).
      CONCLUSIONS: Disparities exist in management of AMI by HIV status. HIV
      seropositive patients were less likely to receive invasive management, CABG, and
      drug-eluting stents, and had higher in-hospital mortality vs patients without
      HIV.

PMID- 27705888
TI  - Randomized trial of switching from prescribed non-selective non-steroidal anti
      inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib
      Outcome Trial (SCOT).
AB  - Background: Selective cyclooxygenase-2 inhibitors and conventional non-selective
      non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with
      adverse cardiovascular (CV) effects. We compared the CV safety of switching to
      celecoxib vs. continuing nsNSAID therapy in a European setting. Method: Patients
      aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from
      established CV disease and taking chronic prescribed nsNSAIDs, were randomized to
      switch to celecoxib or to continue their previous nsNSAID. The primary endpoint
      was hospitalization for non-fatal myocardial infarction or other biomarker
      positive acute coronary syndrome, non-fatal stroke or CV death analysed using a
      Cox model with a pre-specified non-inferiority limit of 1.4 for the hazard ratio
      (HR). Results: In total, 7297 participants were randomized. During a median 3
      year follow-up, fewer subjects than expected developed an on-treatment (OT)
      primary CV event and the rate was similar for celecoxib, 0.95 per 100 patient
      years, and nsNSAIDs, 0.86 per 100 patient-years (HR = 1.12, 95% confidence
      interval, 0.81-1.55; P = 0.50). Comparable intention-to-treat (ITT) rates were
      1.14 per 100 patient-years with celecoxib and 1.10 per 100 patient-years with
      nsNSAIDs (HR = 1.04; 95% confidence interval, 0.81-1.33; P = 0.75). Pre-specified
      non-inferiority was achieved in the ITT analysis. The upper bound of the 95%
      confidence limit for the absolute increase in OT risk associated with celecoxib
      treatment was two primary events per 1000 patient-years exposure. There were only
      15 adjudicated secondary upper gastrointestinal complication endpoints (0.078/100
      patient-years on celecoxib vs. 0.053 on nsNSAIDs OT, 0.078 vs. 0.053 ITT). More
      gastrointestinal serious adverse reactions and haematological adverse reactions
      were reported on nsNSAIDs than celecoxib, but more patients withdrew from
      celecoxib than nsNSAIDs (50.9% patients vs. 30.2%; P < 0.0001). Interpretation:
      In subjects 60 years and over, free from CV disease and taking prescribed chronic
      nsNSAIDs, CV events were infrequent and similar on celecoxib and nsNSAIDs. There
      was no advantage of a strategy of switching prescribed nsNSAIDs to prescribed
      celecoxib. This study excluded an increased risk of the primary endpoint of more
      than two events per 1000 patient-years associated with switching to prescribed
      celecoxib. Clinical Trial Registration:
      https://clinicaltrials.gov/show/NCT00447759; Unique identifier: NCT00447759.

PMID- 27705891
TI  - Comparison of Percutaneous Closure Versus Surgical Femoral Cutdown for
      Decannulation of Large-Sized Arterial and Venous Access Sites in Adults After
      Successful Weaning of Veno-Arterial Extracorporeal Membrane Oxygenation.
AB  - OBJECTIVE: Surgical femoral cutdown for decannulation after veno-arterial
      extracorporeal membrane oxygenation (VA-ECMO) is considered standard practice.
      However, access-site complications with this technique are not rare. The
      objective of this study is to evaluate feasibility, safety, and efficacy of a
      complete percutaneous decannulation procedure after VA-ECMO compared with the
      conventional surgical cutdown approach. METHODS: In 35 patients who were
      successfully weaned from VA-ECMO support, femoral artery and vein access sites
      were closed using a completely percutaneous approach in 15 patients, whereas 20
      patients had conventional surgical cutdown for access-site closure. Data
      concerning all 35 patients were collected retrospectively and analyzed regarding
      immediate vascular closure success, associated complications, and clinical
      outcomes. RESULTS: Technical deployment success of the percutaneous vascular
      closure devices was achieved in all patients. Immediate success of closure was
      achieved more frequently in the surgical group (29% vs 100%; P<.05). Severe wound
      complications requiring surgery occurred only in the surgical group (0% vs 35%;
      P=NS). Surgical cutdown was associated with a significantly greater need for
      transfusion of packed red blood cells (1.6 +/- 1.4 vs 2.2 +/- 1.2; P<.05). Mean
      hospital stay was shorter in the percutaneous group (32 +/- 18 days vs 36 +/- 12
      days; P=NS). One patient in the surgical group complained about sustained
      paresthesia after discharge. CONCLUSIONS: Complete percutaneous closure of the
      femoral access site after VA-ECMO is feasible, effective, and safe when compared
      with conventional surgical closure and performed by experienced operators.

PMID- 27705892
TI  - Sapien 3 Transcatheter Aortic Valve Implantation With Moderate or Without
      Predilation.
AB  - OBJECTIVES: Aortic valve preparation with balloon aortic valvuloplasty (BAV) has
      been previously considered mandatory during transcatheter aortic valve
      implantation (TAVI) procedures. BAV-inherent risks including stroke, conduction
      abnormalities, and reduced device profile size established the rationale for safe
      valve deployment without the need for aggressive valve preparation. We
      investigate the feasibility and safety of performing Sapien 3 (S3; Edwards
      Lifesciences) balloon-expandable TAVI with moderate or without predilation (PD).
      METHODS: We examined consecutive patients with severe aortic stenosis who
      underwent S3-TAVI at our institution. Overall, 119 patients underwent TAVI
      without PD and 126 with moderate PD (mean valvuloplasty balloon diameter, 15.3 +/
      2.1 mm). TAVI endpoints and adverse events were considered according to the
      Valve Academic Research Consortium (VARC)-2 definitions. RESULTS: Device success
      for the entire cohort was 98.8%. PD rates were similar between groups. Total
      fluoroscopy time and amount of contrast used were lower in the no PD group (13
      min vs 16.2 min [P<.001] and 71.3 mL vs 81 mL [P=.03], respectively). All-cause
      mortality up to 30 days was 0% (0/119) in the no PD group vs 1.6% (2/126) in the
      moderate PD group (P=.49). VARC-2 defined complication rates at 30 days including
      cerebrovascular accident were similar between groups. Overall, there was no
      significant difference in survival rate between both groups (hazard ratio, 3.6;
      95% confidence interval, 0.80-16.2; P=.09). CONCLUSIONS: Balloon-expandable TAVI
      using the S3 device with moderate or without balloon PD is feasible and safe.
      Omission of PD in appropriate cases was associated with reduced fluoroscopy time
      and total contrast used without affecting procedural success.

PMID- 27705893
TI  - Balloon Predilation for TAVR: Over-Inflated or Under-Rated?

PMID- 27705894
TI  - Cocaine-Induced Microvascular Dysfunction and its Reversal by Administration of
      Intracoronary Calcium-Channel Blocker.
AB  - A 47-year-old male smoker with recent cocaine use presented with 6 hours of chest
      pain unrelieved by sublingual and intravenous nitroglycerin. To our knowledge,
      this is the first reported case demonstrating the efficacy of an intracoronary
      calcium-channel blocker to ameliorate cocaine-induced microvascular spasm.

PMID- 27705895
TI  - The Absorb Limits.
AB  - A patient presented with an inferior non-ST segment elevation myocardial
      infarction and a tight lesion on the distal right coronary artery. After stent
      implantation, a large scaffold malapposition was observed by optical coherence
      tomography. This case emphasizes the importance of not expanding a bioresorbable
      vascular scaffold more than 0.5 mm over its nominal size.

PMID- 27705896
TI  - Arterial Discordance in Cardiac Tamponade.
AB  - Ventricular interdependence is a salient hemodynamic feature of cardiac tamponade
      that manifests as discordance between the left and right ventricles in filling
      and ejection on hemodynamic assessment. Ventricular interdependence can manifest
      as arterial discordance at the level of the great arteries.

PMID- 27705897
TI  - Contrast Dose, Estimated GFR, and Techniques to Reduce Contrast Dose in PCI -
      Time to Consider Some Basic Principles!

PMID- 27705898
TI  - DNA Vaccines: Regulatory Considerations and Safety Aspects.
AB  - DNA vaccines have great potential as preventive or therapeutic vaccines against
      viral, bacterial, or parasitic diseases as well as cancer, and may also be used
      as gene therapy products. Although many human and veterinary DNA vaccines have
      been investigated in laboratory trials, only four of these have been approved for
      commercial use. In this paper an overview of the regulatory requirements for the
      development of DNA vaccines is given. The regulatory process in EU and USA is
      described. A discussion concerning the relevance of national regulations on gene
      technology is included. In addition the main safety concerns associated with DNA
      vaccines, relating to unwanted side effects in the vaccinated mammal or fish, are
      presented. Finally, the need for greater openness regarding the assessment
      information is discussed.

PMID- 27705899
TI  - Health Advocacy Project: Evaluating the Benefits of Service Learning to Nursing
      Students and Low Income Individuals Involved in a Community-Based Mental Health
      Promotion Project.
AB  - Poverty, along with other factors such as unemployment, work and life stressors,
      interpersonal violence, and lack of access to high quality health and/or social
      services all play a role in determining who develops a mental illness and for
      whom those symptoms persist or worsen. Senior nursing student preparing to enter
      the field and working in a service learning capacity may be able to influence
      early recovery and symptom abatement among those most vulnerable to mental
      illness. A consortium of community stakeholders and researchers collaboratively
      designed a 10-week mental health promotion project called the Health Advocacy
      Project (HAP). The project combines case management and system navigation support
      delivered by trained and highly supervised nursing students to individuals
      experiencing major depressive disorder (MDD) and/or post-traumatic stress
      disorder (PTSD). In this article, we present the findings of a qualitative
      fidelity evaluation that examines the effectiveness of nursing students in
      delivering the health advocacy intervention at the level and with the intensity
      originally intended. The findings demonstrate how the services of senior nursing
      students may be optimized to benefit our healthcare system and populations most
      at risk for developing MDD and PTSD.

PMID- 27705900
TI  - Structural diversity in echinocandin biosynthesis: the impact of oxidation steps
      and approaches toward an evolutionary explanation.
AB  - Echinocandins are an important group of cyclic non-ribosomal peptides with strong
      antifungal activity produced by filamentous fungi from Aspergillaceae and
      Leotiomycetes. Their structure is characterized by numerous hydroxylated non
      proteinogenic amino acids. Biosynthetic clusters discovered in the last years
      contain up to six oxygenases, all of which are involved in amino acid
      modifications. Especially, variations in the oxidation pattern induced by these
      enzymes account for a remarkable structural diversity among the echinocandins.
      This review provides an overview of the current knowledge of echinocandin
      biosynthesis with a special focus on diversity-inducing oxidation steps. The
      emergence of metabolic diversity is further discussed on the basis of a
      comprehensive overview of the structurally characterized echinocandins, their
      producer strains and biosynthetic clusters. For the pneumocandins, echinocandins
      produced by Glarea lozoyensis, the formation of metabolic diversity in a single
      organism is analyzed. It is compared to two common models for the evolution of
      secondary metabolism: the 'target-based' approach and the 'diversity-based'
      model. Whereas the early phase of pneumocandin biosynthesis supports the target
      based model, the diversity-inducing late steps and most oxidation reactions best
      fit the diversity-based approach. Moreover, two types of diversity-inducing steps
      can be distinguished. Although incomplete hydroxylation is a common phenomenon in
      echinocandin production and secondary metabolite biosynthesis in general, the
      incorporation of diverse hydroxyprolines at position 6 is apparently a unique
      feature of pneumocandin biosynthesis, which stands in stark contrast to the
      strict selectivity found in echinocandin biosynthesis by Aspergillaceae. The
      example of echinocandin biosynthesis shows that the existing models for the
      evolution of secondary metabolism can be well applied to parts of the pathway;
      however, thus far, there is no comprehensive theory that could explain the entire
      biosynthesis.

PMID- 27705901
TI  - Training in management of arrhythmias for medical residents: a case-based
      learning strategy.

PMID- 27705902
TI  - Height indicates hematopoietic capacity in elderly Japanese men.
AB  - Previously, we reported that height is an indicator of the capacity of vascular
      repair in elderly men, especially hypertensive men. On the other hand, hemoglobin
      could act as a possible biochemical index of hypertension-induced vascular
      damage. However, no studies have clarified the correlation between height and
      hematopoietic activity. We conducted a cross-sectional study of 249 men aged 65
      69 undergoing a general health check-up. Reticulocyte was used to evaluate
      hematopoietic activity. Because hemoglobin concentration should influence
      hematopoietic activity, analyses stratified by hemoglobin level were performed.
      Independent of known cardiovascular risk factors and other hematological
      parameters (white blood cell count), a significant positive correlation was seen
      between height and reticulocytes for total subjects and subjects with a high
      hemoglobin concentration (>=14.5 g/dL), but not in subjects with a low hemoglobin
      concentration (<14.5 g/dL). The standardized parameter estimates (beta) were
      beta=0.18, p=0.003 for total subjects, beta=0.28, p=0.001 for subjects with a
      high hemoglobin concentration, and beta=0.03, p=0.717 for subjects with low
      hemoglobin. Independently, height is significantly positively correlated with
      reticulocyte in elderly Japanese men, particularly in men with a high hemoglobin
      concentration. These results indicate that subjects with a short stature might
      have lower hematopoietic capacity than those with a high stature.

PMID- 27705903
TI  - Lower mortality rates in those living at moderate altitude.

PMID- 27705904
TI  - A cross-sectional study of male and female C57BL/6Nia mice suggests lifespan and
      healthspan are not necessarily correlated.
AB  - Lifespan provides a discrete metric that is intuitively appealing and the
      assumption has been that healthspan is extended concomitant with lifespan.
      Medicine has been more successful at extending life than preserving health during
      aging. Interventions that extend lifespan in model organisms do not always result
      in a corresponding increase in healthspan, suggesting that lifespan and
      healthspan may be uncoupled. To understand how interventions that extend life
      affect healthspan, we need measures that distinguish between young and old
      animals. Here we measured age-related changes in healthspan in male and female
      C57BL/6JNia mice assessed at 4 distinct ages (4 months, 20 months, 28 months and
      32 months). Correlations between health parameters and age varied. Some
      parameters show consistent patterns with age across studies and in both sexes,
      others changed in one sex only and others showed no significant differences in
      mice of different ages. Few correlations existed among health assays, suggesting
      that physiological function in domains we assessed change independently in aging
      mice. With one exception, health parameters were not significantly associated
      with an increased probability of premature death. Our results show the need for
      more robust measures of murine health and suggest a potential disconnect between
      health and lifespan in mice.

PMID- 27705905
TI  - Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress
      response.
AB  - Adipocytes promote cancer progression and impair treatment, and have been shown
      to protect acute lymphoblastic leukemia (ALL) cells from chemotherapies. Here we
      investigate whether this protection is mediated by changes in oxidative stress.
      Co-culture experiments showed that adipocytes protect ALL cells from oxidative
      stress induced by drugs or irradiation. We demonstrated that ALL cells induce
      intracellular ROS and an oxidative stress response in adipocytes. This adipocyte
      oxidative stress response leads to the secretion of soluble factors which protect
      ALL cells from daunorubicin (DNR). Collectively, our investigation shows that ALL
      cells elicit an oxidative stress response in adipocytes, leading to adipocyte
      protection of ALL cells against DNR.

PMID- 27705907
TI  - The precision relationships between eight GWAS-identified genetic variants and
      breast cancer in a Chinese population.
AB  - Some of the new breast cancer susceptibility loci discovered in recent Genome
      wide association studies (GWASs) have not been confirmed in Chinese populations.
      To determine whether eight novel Single-Nucleotide Polymorphisms (SNPs) have
      associations with breast cancer risk in women from southeast China, we conducted
      a case-control study of 1,156 breast cancer patients and 1,256 healthy controls.
      We first validated that the SNPs rs12922061, rs2290203, and rs2981578 were
      associated with overall breast cancer risk in southeast Chinese women, with the
      per-allele OR of 1.209 (95%CI: 1.064-1.372), 1.176 (95%CI: 1.048-1.320), and
      0.852 (95%CI: 0.759-0.956), respectively. Rs12922061 and rs2290203 even passed
      the threshold for Bonferroni correction (P value: 0.00625). In stratified
      analysis, we found another three SNPs were significantly associated within
      different subgroups. However, after Bonferroni correction (P value: 0.000446),
      there were no statistically significant was observed. In gene-environment
      interaction analysis, we observed gene-environment interactions played a
      potential role of in the risk of breast cancer. These findings provide new
      insight into the associations between the genetic susceptibility and fine
      classifications of breast cancer. Based on these results, we encourage further
      large series studies and functional research to confirm these finding.

PMID- 27705906
TI  - Cyr61-positive cancer stem-like cells enhances distal metastases of pancreatic
      cancer.
AB  - Efficient inhibition of tumor metastasis after resection of primary tumors is
      critical for cancer therapy. We have recently shown that Cyr61 promotes growth of
      pancreatic ductal adenocarcinoma (PDAC) through PI3k/Akt signaling-enhanced
      nuclear exclusion of p27. Here, we report that administration of adeno-associated
      viral vectors carrying a short-hairpin interfering RNA (shRNA) for Cyr61 via
      pancreatic duct significantly decreased the distal tumor metastases after
      resection of primary pancreatic tumor in mice. Moreover, Cyr61 depletion in PDAC
      cells significantly inhibited the tumor sphere formation in vitro, significantly
      decreased the growth of the subcutaneously transplanted tumor, and significantly
      decreased the incidence of tumor formation after serial adoptive transplantation
      into NOD/SCID mice. Finally, higher Cyr61 levels were detected in the PDAC
      specimens from the patients with distal tumor metastasis, compared to PDAC
      without metastasis at diagnosis. Together, our study suggests that suppression of
      Cyr61 in cancer stem cell-like cells in PDAC may inhibit tumor cell metastasis
      after resection of the primary tumor.

PMID- 27705908
TI  - An inhibitor of cholesterol absorption displays anti-myeloma activity by
      targeting the JAK2-STAT3 signaling pathway.
AB  - The activated JAK2-STAT3 signaling pathway is a high risk factor for multiple
      myeloma (MM), a fatal malignancy of plasma cells. In the present study, SC09, a
      potential inhibitor of cholesterol absorption, was identified in a STAT3-targeted
      drug screen. SC09 suppressed the activation of STAT3 in a time-course and
      concentration-dependent manner but did not affect its family members STAT1 and
      STAT5. SC09 inhibited STAT3 transcriptional activity and downregulated the
      expression of STAT3-regulated genes. Further studies showed that SC09 selectively
      inhibited JAK2 activation but not other kinases including c-Src, ERK, p38 and
      mTOR that are all associated with STAT3 activation. Moreover, SC09 obviously
      induced MM cell death in vitro and delayed MM tumor growth in vivo. SC09-induced
      MM cell death was dependent on the endogenous STAT3 status, and this effect could
      be attenuated by enforced expression of STAT3. All the results collectively
      indicated that SC09 blocks the JAK2-STAT3 signaling thus displaying anti-MM
      activity. Given its well tolerance and anti-MM potency, SC09 is credited for
      further investigation as a promising drug for MM treatment.

PMID- 27705909
TI  - PARP1 inhibitor olaparib (Lynparza) exerts synthetic lethal effect against ligase
      4-deficient melanomas.
AB  - Cancer including melanoma may be ''addicted" to double strand break (DSB) repair
      and targeting this process could sensitize them to the lethal effect of DNA
      damage. PARP1 exerts an important impact on DSB repair as it binds to both single
      and double- strand breaks. PARP1 inhibitors might be highly effective drugs
      triggering synthetic lethality in patients whose tumors have germline or somatic
      defects in DNA repair genes. We hypothesized that PARP1-dependent synthetic
      lethality could be induced in melanoma cells displaying downregulation of DSB
      repair genes. We observed that PARP1 inhibitor olaparib sensitized melanomas with
      reduced expression of DNA ligase 4 (LIG4) to an alkylatimg agent dacarbazine
      (DTIC) treatment in vitro, while normal melanocytes remained intact. PARP1
      inhibition caused accumulation of DSBs, which was associated with apoptosis in
      LIG4 deficient melanoma cells. Our hypothesis that olaparib is synthetic lethal
      with LIG4 deficiency in melanoma cells was supported by selective anti-tumor
      effects of olaparib used either alone or in combination with dacarbazine (DTIC)
      in LIG4 deficient, but not LIG4 proficient cells. In addition, olaparib combined
      with DTIC inhibited the growth of LIG4 deficient human melanoma xenografts. This
      work for the first time demonstrates the effectiveness of a combination of PARP1
      inhibitor olaparib and alkylating agent DTIC for treating LIG4 deficient
      melanomas. In addition, analysis of the TCGA and transcriptome microarray
      databases revealed numerous individual melanoma samples potentially displaying
      specific defects in DSB repair pathways, which may predispose them to synthetic
      lethality triggered by PARP1 inhibitor combined with a cytotoxic drug.

PMID- 27705910
TI  - Indoleamine 2,3-dioxygenase regulates anti-tumor immunity in lung cancer by
      metabolic reprogramming of immune cells in the tumor microenvironment.
AB  - Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by
      tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells
      and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment
      (TME), leads to Trp depletion that impairs cytotoxic T cell responses and
      survival; however, exact mechanisms remain incompletely understood. We previously
      reported that a combination therapy of gemcitabine and a superoxide dismutase
      mimetic promotes anti-tumor immunity in a mouse model of lung cancer by
      inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and
      extending survival. Here, we show that combination therapy targets IDO signaling,
      specifically in MDSCs, tumor cells, and CD8+ T cells infiltrating the TME.
      Deficiency of IDO caused significant reduction in tumor burden, tumor
      infiltrating MDSCs, GM-CSF, MDSC survival and infiltration of programmed death
      receptor-1 (PD-1)-expressing CD8+ T cells compared to controls. IDO-/- MDSCs
      downregulated nutrient-sensing AMP-activated protein kinase (AMPK) activity, but
      IDO-/- CD8+ T cells showed AMPK activation associated with enhanced effector
      function. Our studies provide proof-of-concept for the efficacy of this
      combination therapy in inhibiting IDO and T cell exhaustion in a syngeneic model
      of lung cancer and provide mechanistic insights for IDO-dependent metabolic
      reprogramming of MDSCs that reduces T cell exhaustion and regulates anti-tumor
      immunity.

PMID- 27705911
TI  - Targeting SALL4 by entinostat in lung cancer.
AB  - The overall survival of lung cancer patients remains dismal despite the
      availability of targeted therapies. Oncofetal protein SALL4 is a novel cancer
      target. We herein report that SALL4 was aberrantly expressed in a subset of lung
      cancer patients with poor survival. SALL4 silencing by RNA interference or SALL4
      peptide inhibitor treatment led to impaired lung cancer cell growth. Expression
      profiling of SALL4-knockdown cells demonstrated that both the EGFR and IGF1R
      signaling pathways were affected. Connectivity Map analysis revealed the HDAC
      inhibitor entinostat as a potential drug in treating SALL4-expressing cancers,
      and this was confirmed in 17 lung cancer cell lines. In summary, we report for
      the first time that entinostat can target SALL4-positive lung cancer. This lays
      the foundation for future clinical studies evaluating the therapeutic efficacy of
      entinostat in SALL4-positive lung cancer patients.

PMID- 27705912
TI  - TACC3 overexpression in cholangiocarcinoma correlates with poor prognosis and is
      a potential anti-cancer molecular drug target for HDAC inhibitors.
AB  - Histone deacetylases (HDACs) have been implicated in multiple malignant tumors,
      and HDAC inhibitors (HDACIs) exert anti-cancer effects. However, the expression
      of HDACs and the anti-tumor mechanism of HDACIs in cholangiocarcinoma (CCA) have
      not yet been elucidated. In this study, we found that expression of HDACs 2, 3,
      and 8 were up-regulated in CCA tissues and those patients with high expression of
      HDAC2 and/or HDAC3 had a worse prognosis. In CCA cells, two HDACIs, trichostatin
      (TSA) and vorinostat (SAHA), suppressed proliferation and induced apoptosis and
      G2/M cycle arrest. Microarray analysis revealed that TACC3 mRNA was down
      regulated in CCA cells treated with TSA. TACC3 was highly expressed in CCA
      tissues and predicted a poor prognosis in CCA patients. TACC3 knockdown induced
      G2/M cycle arrest and suppressed the invasion, metastasis, and proliferation of
      CCA cells, both in vitro and in vivo. TACC3 overexpression reversed the effects
      of its knockdown. These findings suggest TACC3 may be a useful prognostic
      biomarker for CCA and is a potential therapeutic target for HDACIs.

PMID- 27705913
TI  - Epithelioid peritoneal mesothelioma: a hybrid phenotype within a mesenchymal
      epithelial/epithelial-mesenchymal transition framework.
AB  - The aim of this study was to reconsider the biological characteristics of
      epithelioid malignant peritoneal mesothelioma (E-MpM) in the light of new
      concepts about epithelial mesenchymal transition and mesenchymal epithelial
      reverse transition (EMT/MErT) and the role of epigenetic reprogramming in this
      context. To this end we profiled surgical specimens and derived cells cultures by
      a number of complementary approaches i.e. immunohistochemistry,
      immunofluorescence, in situ hybridization, biochemistry, pluripotent stem cell
      arrays, treatments with cytokines, growth factors and specific inhibitors.The
      analyses of the surgical specimens showed that i) EZH2 is expressed throughout
      the spectrum of MpM, ii) that E-MpM (including the high-grade undifferentiated
      form) are characterised by c-MYC and miRNA 17-5p expression, and iii) that
      progression to sarcomatoid MpM is dictated by EMT regulators. They also showed
      that E-MpM expressed c-MET and are enriched in E- and P-cadherins- and VEGFR2
      expressing CSCs, thus strongly supporting a role for MErT reprogramming in
      endowing E-MpM tumour cells with stemness and plasticity, and hence with a drug
      resistant phenotype. The cell culture-based experiments confirmed the stemness
      traits and plasticity of E-MpM, and support the view that EZH2 is a druggable
      target in this tumor.

PMID- 27705914
TI  - Extrachromosomal HPV-16 LCR transcriptional activation by HDACi opposed by
      cellular differentiation and DNA integration.
AB  - Histone deacetylase inhibitors (HDACi) have been shown to render HPV-carrying
      cells susceptible to intrinsic and extrinsic apoptotic signals. As such, these
      epigenetic drugs have entered clinical trials in the effort to treat cervical
      cancer. Here, we studied the effect of common HDACi, with an emphasis on
      Trichostatin A (TSA), on the transcriptional activity of the HPV-16 Long Control
      Region (LCR) in order to better understand the impact of these agents in the
      context of the HPV life cycle and infection. HDACi strongly induced transcription
      of the firefly luciferase reporter gene under the control of the HPV-16 LCR in a
      variety of cell lines. In the HaCaT keratinocyte cell line undergoing
      differentiation induced by TSA, we observed a reduction in LCR-controlled
      transcription. Three major AP-1 binding sites in the HPV-16 LCR are involved in
      the regulation by TSA. However, whatever the status of differentiation of the
      HaCaT cells, TSA induced integration of extra-chromosomal transfected DNA into
      the cellular genome. Although these data suggest caution using HDACi in the
      treatment of HR HPV infection, further in vivo studies are necessary to better
      assess the risk.

PMID- 27705915
TI  - LKB1 is a DNA damage response protein that regulates cellular sensitivity to PARP
      inhibitors.
AB  - Liver kinase B1 (LKB1) functions as a tumor suppressor encoded by STK11, a gene
      that mutated in Peutz-Jeghers syndrome and in sporadic cancers. Previous studies
      showed that LKB1 participates in IR- and ROS-induced DNA damage response (DDR).
      However, the impact of LKB1 mutations on targeted cancer therapy remains unknown.
      Herein, we demonstrated that LKB1 formed DNA damage-induced nuclear foci and co
      localized with ataxia telangiectasia mutated kinase (ATM), gamma-H2AX, and breast
      cancer susceptibility 1 (BRCA1). ATM mediated LKB1 phosphorylation at Thr 363
      following the exposure of cells to ionizing radiation (IR). LKB1 interacted with
      BRCA1, a downstream effector in DDR that is recruited to sites of DNA damage and
      functions directly in homologous recombination (HR) DNA repair. LKB1 deficient
      cells exhibited delayed DNA repair due to insufficient HR. Notably, LKB1
      deficiency sensitized cells to poly (ADP-ribose) polymerase (PARP) inhibitors.
      Thus, we have demonstrated a novel function of LKB1 in DNA damage response.
      Cancer cells lacking LKB1 are more susceptible to DNA damage-based therapy and,
      in particular, to drugs that further impair DNA repair, such as PARP inhibitors.

PMID- 27705916
TI  - Asporin enhances colorectal cancer metastasis through activating the
      EGFR/src/cortactin signaling pathway.
AB  - Asporin has been implicated as an oncogene in various types of human cancers;
      however, the roles of asporin in the development and progression of colorectal
      cancer (CRC) have not yet been determined. With clinical samples, we found that
      asporin was highly expressed in CRC tissues compared to adjacent normal tissues
      and the asporin expression levels were significantly associated with lymph node
      metastasis status and TNM stage of the patients. Through knockdown of asporin in
      CRC cell lines RKO and SW620 or overexpression of asporin in cell lines HT-29 and
      LoVo, we found that asporin could enhance wound healing, migration and invasion
      abilities of the CRC cells. Further more, with the human umbilical vein
      endothelial cells (HUVECs) tube formation assays and the xenograft model, we
      found that asporin promoted the tumor growth through stimulating the VEGF
      signaling pathway. The portal vein injection models suggested that asporin
      overexpression stimulated the liver metastasis of HT29 cell line, while asporin
      knockdown inhibited the liver metastasis of RKO cell line. In addition, asporin
      was found to augment the phosphorylation of EGFR/src/cortactin signaling pathway,
      which might be contributed to the biological functions of asporin in CRC
      metastasis. These results suggested that asporin promoted the tumor growth and
      metastasis of CRC, and it could be a potential therapeutic target for CRC
      patients in future.

PMID- 27705917
TI  - Reciprocal regulation of the cholinic phenotype and epithelial-mesenchymal
      transition in glioblastoma cells.
AB  - Glioblastoma (GBM) is the most malignant brain tumor with very limited
      therapeutic options. Standard multimodal treatments, including surgical resection
      and combined radio-chemotherapy do not target the most aggressive subtype of
      glioma cells, brain tumor stem cells (BTSCs). BTSCs are thought to be responsible
      for tumor initiation, progression, and relapse. Furthermore, they have been
      associated with the expression of mesenchymal features as a result of epithelial
      mesenchymal transition (EMT) thereby inducing tumor dissemination and chemo
      resistance. Using high resolution proton nuclear magnetic resonance spectroscopy
      (1H NMR) on GBM cell cultures we provide evidence that the expression of well
      known EMT activators of the ZEB, TWIST and SNAI families and EMT target genes N
      cadherin and VIMENTIN is associated with aberrant choline metabolism. The
      cholinic phenotype is characterized by high intracellular levels of
      phosphocholine and total choline derivatives and was associated with malignancy
      in various cancers. Both genetic and pharmacological inhibition of the cardinal
      choline metabolism regulator choline kinase alpha (CHKalpha) significantly
      reduces the cell viability, invasiveness, clonogenicity, and expression of EMT
      associated genes in GBM cells. Moreover, in some cell lines synergetic cytotoxic
      effects were observed when combining the standard of care chemotherapeutic
      temozolomide with the CHKalpha inhibitor V-11-0711. Taken together, specific
      inhibition of the enzymatic activity of CHKalpha is a powerful strategy to
      suppress EMT which opens the possibility to target chemo-resistant BTSCs through
      impairing their mesenchymal transdifferentiation. Moreover, the newly identified
      EMT-oncometabolic network may be helpful to monitor the invasive properties of
      glioblastomas and the success of anti-EMT therapy.

PMID- 27705919
TI  - Exploring timing activation of functional pathway based on differential co
      expression analysis in preimplantation embryogenesis.
AB  - Recent genome-wide omics studies have confirmed the early embryogenesis strictly
      dependent on the rigorous spatiotemporal activation and multilevel regulation.
      However, the full effect of functional pathway was not considered. To obtain
      complete understanding of the gene activation during early development, we
      performed systematic comparisons based on differential co-expression analysis for
      bovine preimplantation embryo development (PED). The results confirmed that the
      functional pathways actively transcribes as early as the 2-cell and 4-cell waves,
      which Basal transcription factor, Endocytosis and Spliceosome pathway can
      represent first signs of embryonic activity. Endocytosis act as one of master
      activators for uncovering a series of successive waves of maternal pioneer signal
      regulator with the help of Spliceosome complex. Furthermore, the results showed
      that pattern recognition receptors began to perform its essential function at 4
      cell stage, which might be needed to coordinate the later major activation. And
      finally, our work presented a probable dynamic landscape of key functional
      pathways for embryogenesis. A clearer understanding of early embryo development
      will be helpful for Assisted Reproductive Technology (ART) and Regenerative
      Medicine (RM).

PMID- 27705918
TI  - MicroRNA-382-5p aggravates breast cancer progression by regulating the
      RERG/Ras/ERK signaling axis.
AB  - Aberrant activation of the Ras/ERK pathway mediates breast cancer initiation and
      aggressiveness. Therefore, it is important to identify miRNAs that modulate the
      Ras/ERK pathway during breast carcinogenesis and progression. The Ras GTPase
      superfamily member RERG (Ras-related and estrogen-regulated growth inhibitor)
      acts as a tumor suppressor to reduce breast cancer cell proliferation and tumor
      formation and has been suggested to have a regulatory role in the Ras/ERK
      pathway. In this study, we found that RERG exerted its tumor suppressor role by
      attenuating the activation of Ras/ERK signaling effectors. Furthermore, we found
      that miR-382-5p directly targets and represses RERG to attenuate the inhibitory
      effects of RERG on the oncogenic Ras/ERK pathway. Thereby, miR-382-5p promoted
      breast cancer cell viability, clonogenicity, survival, migration, invasion and in
      vivo tumorigenesis/metastasis. In clinical interpretation, miR-382-5p expression
      was negatively correlated with RERG expression, and it also significantly
      functioned as an independent oncomiR for the higher incidence and poorer
      prognosis of breast cancer. This novel connection highlights new diagnostic and
      prognostic roles for miR-382-5p and RERG in breast cancer.

PMID- 27705920
TI  - Integrative analysis of protein-coding and non-coding RNAs identifies clinically
      relevant subtypes of clear cell renal cell carcinoma.
AB  - Protein-coding genes and non-coding RNAs cooperate mutually in cells. Integrative
      analysis of protein-coding and non-coding RNAs may facilitate characterizing
      tumor heterogeneity. We introduced integrated consensus clustering (ICC) method
      to integrate mRNA, miRNA and lncRNA expression profiles of 431 primary clear cell
      renal cell carcinomas (ccRCCs). We identified one RCC subgroup easily
      misdiagnosed as ccRCC in clinic and four robust ccRCC subtypes associated with
      distinct clinicopathologic and molecular features. In subtype R1, AMPK signaling
      pathway is significantly upregulated, which may improve the oncologic-metabolic
      shift and partially account for its best prognosis. Subtype R2 has more
      chromosomal abnormities, higher expression of cell cycle genes and less
      expression of genes in various metabolism pathways, which may explain its more
      aggressive characteristic and the worst prognosis. Moreover, much more miRNAs and
      lncRNAs are significantly upregulated in R2 and R4 respectively, suggesting more
      important roles of miRNAs in R2 and lncRNAs in R4. Triple-color co-expression
      network analysis identified 28 differentially expressed modules, indicating the
      importance of cooperative regulation of mRNAs, miRNAs and lncRNAs in ccRCC. This
      study establishes an integrated transcriptomic classification which may
      contribute to understanding the heterogeneity and implicating the treatment of
      ccRCC.

PMID- 27705921
TI  - miRNAs in acute myeloid leukemia.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs found throughout the eukaryotes
      that control the expression of a number of genes involved in commitment and
      differentiation of hematopoietic stem cells and tumorigenesis. Widespread
      dysregulation of miRNAs have been found in hematological malignancies, including
      human acute myeloid leukemia (AML). A comprehensive understanding of the role of
      miRNAs within the complex regulatory networks that are disrupted in malignant AML
      cells is a prerequisite for the development of therapeutic strategies employing
      miRNA modulators. Herein, we review the roles of emerging miRNAs and the miRNAs
      regulatory networks in AML pathogenesis, prognosis, and miRNA-directed therapies.

PMID- 27705922
TI  - Umbilical cord-derived mesenchymal stem cells reversed the suppressive deficiency
      of T regulatory cells from peripheral blood of patients with multiple sclerosis
      in a co-culture - a preliminary study.
AB  - The immunoregulatory function of T regulatory cells (Tregs) is impaired in
      multiple sclerosis (MS). Recent studies have shown that umbilical cord-derived
      mesenchymal stem cells (UC-MSCs) exert regulatory effect on the functions of
      immune cells. Thus, we investigated whether UC-MSCs could improve the impaired
      function of Tregs from MS patients. Co-cultures of UC-MSCs with PBMCs of MS
      patients were performed for 3 days. Flow cytometry was used to determine the
      frequency of Tregs. A cell proliferation assay was used to evaluate the
      suppressive capacity of Tregs. ELISA was conducted for cytokine analysis in the
      co-cultures. Our results showed that UC-MSCs significantly increased the
      frequency of CD4+CD25+CD127low/- Tregs in resting CD4+ T cells (p<0.01) from MS,
      accompanied by the significantly augmented production of cytokine prostaglandin
      E2, transforming growth factor (-beta1, and interleukin-10, along with a reduced
      interferon-gamma production in these co-cultures (p<0.05 - 0.01). More
      importantly, UC-MSC-primed Tregs of MS patients significantly inhibited the
      proliferation of PHA-stimulated autologous and allogeneic CD4+CD25- T effector
      cells (Teffs) from MS patients and healthy individuals compared to non-UC-MSC
      primed (naive) Tregs from the same MS patients (p<0.01). Furthermore, no
      remarkable differences in suppressing the proliferation of PHA-stimulated
      CD4+CD25- Teffs was observed in UC-MSC-primed Tregs from MS patients and naive
      Tregs from healthy subjects. The impaired suppressive function of Tregs from MS
      can be completely reversed in a co-culture by UC-MSC modulation. This report is
      the first to demonstrate that functional defects of Tregs in MS can be repaired
      in vitro using a simple UC-MSC priming approach.

PMID- 27705924
TI  - A mixed analysis comparing nine minimally invasive surgeries for unresectable
      hepatocellular carcinoma patients.
AB  - Hepatocellular carcinoma (HCC) is usually managed by the transcatheter arterial
      chemoembolization (TACE). However, this technique has been challenged since
      severe complications have been observed in clinical practices. As a result,
      clinicians have started to seek other minimally invasive surgeries with
      equivalent efficacy. The corresponding surgeries were assessed by the five
      outcomes: complete response (CR), partial response (PR), stable disease (SD),
      progression disease (PD) and objective response rate (ORR). Direct meta-analysis
      and network meta-analysis were performed and the results were represented by odds
      ratios (OR), 95% confidence and credential intervals. Furthermore, the value of
      surface under the cumulative ranking curve (SUCRA)was calculated to provide
      corresponding rankings.Seventeen studies were incorporated into the network meta
      analysis which indicated that TACE + external-beam radiation therapy (EBRT) and
      drug-eluting beads (DEB) were better than TACE at controllingPD. TACE + EBRT
      demonstrated their advantages compared to TARE-90Y.However, network meta-analysis
      comparison showed no significant difference between the corresponding eight
      treatments with respect to CR, PR, SD and ORR. Moreover, the SUCRA suggested that
      TACE+EBRT were better than other treatments at treating unresectableHCC.Based on
      the present results of this network meta-analysis, TACE + EBRT was more effective
      than the other seven minimally invasive surgeries and therefore it is considered
      as the optimal treatment for HCC.

PMID- 27705923
TI  - Mucins and associated O-glycans based immunoprofile for stratification of
      colorectal polyps: clinical implication for improved colon surveillance.
AB  - Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal
      cancer that are difficult to distinguish histologically from hyperplastic polyps
      (HP) of minimal to no malignant potential. Specific markers for differentiating
      SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The
      present study investigates the potential of mucins and associated O-glycans to
      distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2,
      and MUC5AC) and O-glycans [Sialyl LewisA (CA19-9) and Tn/Sialyl-Tn on MUC1] were
      analyzed in HP (n=33), SSA/P (n=39), and tubular adenoma (TA) (n=36) samples by
      immunohistochemistry. A significantly reduced expression of MUC4 (p=0.0066),
      elevated expression of MUC17 (p=0.0002), and MUC5AC (p<0.0001) was observed in
      SSA/P cases in comparison to HP cases. Interestingly, significantly higher number
      of SSA/P cases (p<0.0001) exhibited MUC5AC expression in the goblet cells as well
      as filled the crypt lumen compared to only goblet cells in majority of the HP
      cases. Improved diagnostic potential was revealed by multivariate logistic
      regression analysis where combinatorial panel of MUC5AC/MUC17 discriminated SSA/P
      from HP (SN/SP=85/82%). Finally, the decision tree model based marker panel (CA19
      9/MUC17/MUC5AC) predicted HP, SSA/P and TA with SN/SP of 58%/95%, 79%/90% and
      97%/83%, respectively. Overall, the mucin and associated O-glycan based panel
      defined in the present study could aid in discriminating SSA/P from HP to devise
      better colon surveillance strategies.

PMID- 27705925
TI  - Mutational load of the mitochondrial genome predicts pathological features and
      biochemical recurrence in prostate cancer.
AB  - Prostate cancer management is complicated by extreme disease heterogeneity, which
      is further limited by availability of prognostic biomarkers. Recognition of
      prostate cancer as a genetic disease has prompted a focus on the nuclear genome
      for biomarker discovery, with little attention given to the mitochondrial genome.
      While it is evident that mitochondrial DNA (mtDNA) mutations are acquired during
      prostate tumorigenesis, no study has evaluated the prognostic value of mtDNA
      variation. Here we used next-generation sequencing to interrogate the
      mitochondrial genomes from prostate tissue biopsies and matched blood of 115 men
      having undergone a radical prostatectomy for which there was a mean of 107 months
      clinical follow-up. We identified 74 unique prostate cancer specific somatic
      mtDNA variants in 50 patients, providing significant expansion to the growing
      catalog of prostate cancer mtDNA mutations. While no single variant or variant
      cluster showed recurrence across multiple patients, we observe a significant
      positive correlation between the total burden of acquired mtDNA variation and
      elevated Gleason Score at diagnosis and biochemical relapse. We add to
      accumulating evidence that total acquired genomic burden, rather than specific
      mtDNA mutations, has diagnostic value. This is the first study to demonstrate the
      prognostic potential of mtDNA mutational burden in prostate cancer.

PMID- 27705926
TI  - Caveolin-1 controls mitochondrial function through regulation of m-AAA
      mitochondrial protease.
AB  - Mitochondrial proteases ensure mitochondrial integrity and function after
      oxidative stress by providing mitochondrial protein quality control. However, the
      molecular mechanisms that regulate this basic biological function in eukaryotic
      cells remain largely unknown. Caveolin-1 is a scaffolding protein involved in
      signal transduction. We find that AFG3L2, a m-AAA type of mitochondrial protease,
      is a novel caveolin-1-interacting protein in vitro. We show that oxidative stress
      promotes the translocation of both caveolin-1 and AFG3L2 to mitochondria,
      enhances the interaction of caveolin-1 with AFG3L2 in mitochondria and stimulates
      mitochondrial protease activity in wild-type fibroblasts. Localization of AFG3L2
      to mitochondria after oxidative stress is inhibited in fibroblasts lacking
      caveolin-1, which results in impaired mitochondrial protein quality control, an
      oxidative phosphorylation to aerobic glycolysis switch and reduced ATP
      production. Mechanistically, we demonstrate that a lack of caveolin-1 does not
      alter either mitochondrial number or morphology but leads to the cytoplasmic and
      proteasome-dependent degradation of complexes I, III, IV and V upon oxidant
      stimulation. Restoration of mitochondrial respiratory chain complexes in caveolin
      1 null fibroblasts reverts the enhanced glycolysis observed in these cells.
      Expression of a mutant form of AFG3L2, which has reduced affinity for caveolin-1,
      fails to localize to mitochondria and promotes degradation of complex IV after
      oxidative stress. Thus, caveolin-1 maintains mitochondrial integrity and function
      when cells are challenged with free radicals by promoting the mitochondrial
      localization of m-AAA protease and its quality control functions.

PMID- 27705927
TI  - Heparan sulfate hexasaccharide selectively inhibits cancer stem cells self
      renewal by activating p38 MAP kinase.
AB  - Heparan sulfate (HS) plays a role in the majority of essential hallmarks of
      cancer, yet its ability to modulate self-renewal, especially of cancer stem cells
      (CSCs), remains unknown. We have discovered that a non-anticoagulant HS
      hexasaccharide (HS06) sequence, but not other shorter or longer sequences,
      selectively inhibited CSC self-renewal and induced apoptosis in colorectal,
      pancreatic, and breast CSCs suggesting a very general phenomenon. HS06 inhibition
      of CSCs relied upon early and sustained activation of p38alpha/beta mitogen
      activated protein kinase (MAPK) but not other MAPKs family members i.e. ERK and
      JNK. In contrast, polymeric HS induced exactly opposite changes in MAPK
      activation and failed to inhibit CSCs. In fact, TCF4 signaling, a critical
      regulator of CSC self-renewal, was inhibited by HS06 in a p38 activation
      dependent fashion. In conclusion, HS06 selectively inhibits CSCs self-renewal by
      causing isoform specific activation of p38MAPK to inhibit TCF4 signaling. These
      observations on chain length-induced specificity carry major mechanistic
      implications with regard to HS in cancer biology, while also presenting a novel
      paradigm for developing novel anti-CSC hexasaccharides that prevent cancer
      relapse.Heparan sulfate (HS) of specific length, i.e., hexasaccharide (HS06), but
      not longer or shorter sequences, selectively inhibit cancer stem cells (CSCs)
      through isoform specific activation of p38 mitogen-activated protein kinase.
      These findings will have major implication for developing chemical probes to
      decipher complex signaling events that govern cancer stem cells. Additionally,
      there are direct implications for designing glycosaminoglycan based cancer
      therapies to selectively target CSCs that escape killing by traditional
      chemotherapy threatening cancer relapse.

PMID- 27705928
TI  - Unraveling the expression of the oncogene YAP1, a Wnt/beta-catenin target, in
      adrenocortical tumors and its association with poor outcome in pediatric
      patients.
AB  - BACKGROUND: Overexpression of the oncogene yes-associated-protein-1 (YAP1) is
      associated with increased cell proliferation in human cancers. YAP1 is a
      potential target of the Wnt/beta-catenin pathway, which plays an important role
      in adrenocortical tumors (ACT). The role of YAP1 in adrenocortical tumorigenesis
      has not been assessed. AIMS: To evaluate YAP1 expression in normal adrenals and
      pediatric ACT and its association with disease outcome. To investigate the
      interaction between YAP1 and the Wnt/beta-catenin pathway in adrenocortical
      cells. RESULTS: Strong YAP1 staining was present in fetal adrenals and pediatric
      ACT but weak in postnatal adrenals. In pediatric ACT, YAP1 mRNA overexpression
      was associated with death, recurrent/metastatic disease and lower overall
      survival. The inhibition of the Wnt/beta-catenin pathway increased YAP1 mRNA
      expression. siYAP1 increased CTNNB1/beta-catenin expression and nuclear staining
      regardless of DLV2, moreover, it decreased cell growth and impaired cell
      migration. MATERIALS AND METHODS: We assessed in 42 pediatric ACT samples the
      YAP1 protein expression by immunohistochemistry and mRNA expression by RT-qPCR
      and analyzed their association with outcome. As controls, we resort 32 fetal and
      postnatal normal adrenals for IHC and 10 normal adrenal cortices for RT-qPCR. The
      interaction between YAP1 and the Wnt/beta-catenin pathway was assessed in NCI
      H295 adrenocortical cells by inhibiting the TCF/beta-catenin complex and by
      knocking down YAP1. CONCLUSION: YAP1 overexpression is a marker of poor prognosis
      for pediatric patients with ACT. In adrenocortical cells, there is a close
      crosstalk between YAP1 and Wnt/beta-catenin. These data open the possibility of
      future molecular therapies targeting Hippo/YAP1 signaling to treat advanced ACT.

PMID- 27705930
TI  - Pyroptosis is involved in the pathogenesis of human hepatocellular carcinoma.
AB  - Pyroptosis is a caspase-1 dependent programmed cell death, which is involved in
      the pathologic process of several kinds of cancers. Loss of caspase-1 gene
      expression has been observed in prostate and gastric cancers. However, the role
      of pyroptosis in human hepatocellular carcinoma (HCC) remains largely unknown.
      The aim of this study was to investigate the involvement of pyroptosis in the
      pathogenesis of HCC. Our study showed that pyroptosis was inhibited in HCC
      tissues and cells. Administration of berberine inhibited the viability, migration
      and invasion capacity of HepG2 cells through the induction of pyroptosis both in
      vitro and in vivo, which was attenuated by caspase-1 inhibitor Ac-YVAD-CMK.
      Conclusively, pyroptosis is involved in the pathogenesis of HCC, and may be a new
      neoplastic target for the treatment of HCC.

PMID- 27705929
TI  - A 5-day cytoreductive chemotherapy followed by haplo-identical hsct (FA5-BUCY) as
      a tumor-ablative regimen improved the survival of patients with advanced
      hematological malignancies.
AB  - Haplo-HSCT has been used when HLA-matched siblings are not available.
      Conditioning regimens aim to reduce tumor burden prior to HSCT and provide
      sufficient immunoablation. We report the outcome of haplo-HSCT in 63 consecutive
      patients from 2/2013 to 12/2015 (19 females/44 males) with high-risk or
      relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5
      advanced-MDS; 2-CML-BC). Median age was 20 years (range: 1.1-49). Twenty-one
      patients achieved remission prior to transplant, while 42 did not. Patients
      received FA5-BUCY, i.e., 5-day salvage chemotherapy (Fludarabine/Ara-C) and
      conditioning (Busulfan/Cyclophosphamide). GvHD prophylaxis included ATG, CsA, MMF
      and short-term MTX. All patients received stem cells from bone marrow and
      peripheral blood, and achieved successful engraftment, except two who died
      before. With a median follow-up of 269 days (120-1081), 42/63 patients are still
      alive and disease-free. Two-year OS and RFS were similar in patients not in
      remission and in those in complete remission (61.3% vs 56.3%, p=0.88; 58.3% vs
      56.3%, p=0.991). Non-relapse mortality and relapse incidence were 22.2% and
      11.1%, respectively. Severe acute-GvHD occurred in 4/63 patients. Transplant
      related mortality was low at day+100 (17.5%) and for the entire study period
      (20.6%). Unexpectedly, few patients experienced mild-to-moderate toxicity, and
      main causes of death were infection and GvHD. BM blast counts, age, and donor
      recipient gender-pairs did not affect the outcome. Less chemotherapy cycles prior
      to HSCT might result in more favorable outcome. Thus, haplo-HSCT with FA5-BUCY
      appears promising for advanced disease, especially when TBI and amsacrine, used
      for FLAMSA, are not available and in pediatric patients for whom TBI is not
      recommended.

PMID- 27705931
TI  - miR128-1 inhibits the growth of glioblastoma multiforme and glioma stem-like
      cells via targeting BMI1 and E2F3.
AB  - MicroRNA128-1 (miR128-1), as a brain-specific miRNA, is downregulated in
      glioblastoma multiforme (GBM) and closely associated with the progression of GBM.
      However, the underlying molecular mechanism of the downregulation and its role in
      the regulation of tumorigenesis and anticancer drug resistance in GBM remains
      largely unknown. In the current study,we found that miR128-1 was downregulated in
      GBM and glioma stem-like cells (GSCs). Intriguingly, treatment with the DNA
      methylation inhibitors 5-Aza-CdR (Aza) and 4-phenylbutyric acid (PBA) resulted in
      miR128-1 upregulation in both GBM cells and GSCs. Either forced expression of
      miR128-1 or Aza/PBA treatment inhibited tumor cell proliferation, migration and
      invasion in vitro. Moreover, overexpression of miR128-1 inhibited the growth of
      transplant tumor in vivo. BMI1 and E2F3 were found to be direct targets of miR128
      1 and downregulated by miR128-1 in vitro and in vivo. Our results revealed a
      mechanism of methylation that controls miR128-1 expression in GBM cells and GSCs
      and indicate miR128-1 could function as a tumor suppressor in GBM by negatively
      regulating tumor cell proliferation, invasion and self-renewal through direct
      targeting BMI1 and E2F3. Our findings suggest that DNA methylation inhibitors are
      potential agents for GBM treatment by upregulating miR-128-1.

PMID- 27705932
TI  - KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case
      control.
AB  - The utility of KRAS mutations in plasma circulating cell-free DNA (cfDNA) samples
      as non-invasive biomarkers for the detection of pancreatic cancer has never been
      evaluated in a large case-control series. We applied a KRAS amplicon-based deep
      sequencing strategy combined with analytical pipeline specifically designed for
      the detection of low-abundance mutations to screen plasma samples of 437
      pancreatic cancer cases, 141 chronic pancreatitis subjects, and 394 healthy
      controls. We detected mutations in 21.1% (N=92) of cases, of whom 82 (89.1%)
      carried at least one mutation at hotspot codons 12, 13 or 61, with mutant allelic
      fractions from 0.08% to 79%. Advanced stages were associated with an increased
      proportion of detection, with KRAS cfDNA mutations detected in 10.3%, 17,5% and
      33.3% of cases with local, regional and systemic stages, respectively. We also
      detected KRAS cfDNA mutations in 3.7% (N=14) of healthy controls and in 4.3%
      (N=6) of subjects with chronic pancreatitis, but at significantly lower allelic
      fractions than in cases. Combining cfDNA KRAS mutations and CA19-9 plasma levels
      on a limited set of case-control samples did not improve the overall performance
      of the biomarkers as compared to CA19-9 alone. Whether the limited sensitivity
      and specificity observed in our series of KRAS mutations in plasma cfDNA as
      biomarkers for pancreatic cancer detection are attributable to methodological
      limitations or to the biology of cfDNA should be further assessed in large case
      control series.

PMID- 27705933
TI  - Definition and characterization of novel HLA-*A02-restricted CD8+ T cell epitopes
      derived from JCV polyomavirus with clinical relevance.
AB  - Human JC and BK polyomaviruses (JCV/BKV) can establish a latent infection without
      any clinical symptoms in healthy individuals. In immunocompromised hosts
      infection or reactivation of JCV and BKV can cause lethal progressive multifocal
      leukoencephalopathy (PML) and hemorrhagic cystitis, respectively. Vaccination
      with JCV/BKV derived antigen epitope peptides or adoptive transfer of virus
      specific T cells would constitute an elegant approach to clear virus-infected
      cells. Furthermore, donor leukocyte infusion (DLI) is another therapeutic
      approach which could be helpful for patients with JCV/BKV infections.So far, only
      few immunodominant T cell epitopes of JCV and BKV have been described and
      therefore is a fervent need for the definition of novel epitopes. In this study,
      we identified novel T cell epitopes by screening libraries of overlapping
      peptides derived from the major capsid protein VP1 of JCV. Virus like particles
      (VLPs) were used to confirm naturally processing. Two human leucocyte antigen
      (HLA)-A*02-restricted epitopes were characterized by fine mapping with
      overlapping peptides and nonamer peptide sequences were identified. Cytokine
      release profile of the epitope-specific T cells was analyzed by enzyme-linked
      immunospot (ELISPOT) assays and by flow cytometry. We demonstrated that T cell
      responses were of polyfunctional nature with the potential of epitope-specific
      killing and cross-reactivity between JCV and BKV. These novel epitopes might
      constitute a new potential tool to design effective diagnostic and therapeutic
      approaches against both polyomaviruses.

PMID- 27705934
TI  - Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT
      signaling.
AB  - Hypervascularity is one of the main characteristics of hepatocellular carcinoma
      (HCC). However, the mechanisms of angiogenesis in HCC remain controversial. In
      this study, we investigate the role of Notch1 in angiogenesis of HCC. We found
      that Notch1 expression was correlated with formation of vasculogenic mimicry (VM)
      and expression of biomarkers of epithelial-to-mesenchymal transition (EMT) in the
      tumor specimens. Two HCC cell lines, HepG2 and MHCC97-H, with low and high Notch1
      expression, respectively, were used to study the mechanism of VM formation both
      in vitro and in vivo. It was found that MHCC97-H cells, but not HepG2 cells form
      VM when they grow on matrigel in vitro. HepG2 cells gained the power of forming
      VM when they were overexpressed with Notch1, while knockdown Notch1 expression in
      MHCC97-H cells led to the loss of VM forming ability of the cells. Similar
      results were found in in vivo study. High expression of Notch1 in HepG2 promoted
      xenograft growth in nude mice, with abundant VM formation in the tumor samples.
      Moreover, we observed Notch1 was associated with the EMT and malignant behavior
      of hepatocellular carcinoma by analyzing clinical specimens, models for in vitro
      and in vivo experiments. HepG2 presented EMT phenomenon when induced by TGF
      beta1, accompanied by Notch1 activation while MHCC97-H with knockdown of Notch1
      lost the responsiveness to TGF-beta1 induction. Our results suggest that Notch1
      promotes HCC progression through activating EMT pathway and forming VM. Our
      results will guide targeting Notch1 in new drug development.

PMID- 27705935
TI  - Circulating microRNA124-3p, microRNA9-3p and microRNA196b-5p may be potential
      signatures for differential diagnosis of thyroid nodules.
AB  - It is important to develop an effective auxiliary approach to distinguish
      papillary thyroid carcinoma (PTC) from benign nodules because a considerable
      proportion cannot be identified by fine-needle aspiration cytology at present,
      resulting in unnecessary thyroidectomy. Circulating miRNAs are potential
      biomarkers for differential diagnosis of tumors. We aimed to investigate the
      dysregulation of circulating miRNAs in PTC and evaluate the diagnostic value for
      differentiation of PTC from benign nodules. We first assessed the expression of
      miRNAs in patients with PTC, patients with benign nodules and healthy controls
      using a miRCURY LNA Array (n = 3 for each group). Expression of circulating miR
      124-3p, miR-9-3p and miR-5691 was significantly up-regulated, while miR-4701 and
      miR-196b-5p were down-regulated in PTC patients. The dysregulation of miR-124-3p,
      miR-9-3p, miR-4701 and miR-196b-5p was further validated by qRT-PCR in fifty
      participants from each group. The expression of circulating miR-124-3p and miR-9
      3p was significantly up-regulated in PTC patients. Both miR-124-3p and miR-9-3p
      could distinguish PTC from benign nodules with high sensitivity and specificity.
      There were no significant differences in the expression of circulating miR-4701
      and miR-196b-5p between PTC patients and healthy controls. Nevertheless, patients
      with benign nodules showed a higher level of miR-196b-5p compared with that of
      PTC patients and healthy controls. ROC analysis indicated that miR-196b-5p had a
      good diagnostic value for differentiation of benign nodules from PTC. Our study
      suggested that miR-124-3p, miR-9-3p and miR-196b-5p may be potential signatures
      for differential diagnosis of thyroid nodules in eastern coastal areas of China.

PMID- 27705936
TI  - Meta-analysis of gene expression and integrin-associated signaling pathways in
      papillary renal cell carcinoma subtypes.
AB  - Papillary renal cell carcinoma (PRCC) is the second most common renal cell
      carcinoma (RCC) that can be further subdivided into type 1 (PRCC1) and type 2
      (PRCC2) RCCs based on histological and genetic features. PRCC2 is often more
      aggressive than PRCC1. While integrin-associated protein complexes mediate
      tumorigenesis and metastases in many types of cancers it is not known whether
      integrin-mediated signaling impacts PRCC and differs between PRCC1 and PRCC2. In
      this study, we combined the analysis of five PRCC gene expression datasets
      derived from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) by
      using integrative bioinformatics pipelines. We found 1475 differentially
      expressed genes among which 37 genes were associated with integrin pathways. In
      comparison with PRCC1, PRCC2 cases showed upregulated expression of alpha5
      integrin (ITGA5) whereas the expression of alpha6- (ITGA6) and beta8-integrins
      (ITGB8) was downregulated. Because PRCC2 occurs more frequently in men, the meta
      analysis was extended to explore the gender effects. This analysis revealed 8
      genes but none of them was related to integrin pathways suggesting that other
      mechanisms than integrin-mediated signaling underlie the observed gender
      differences in the pathogenicity of PRCC2.

PMID- 27705937
TI  - Metformin potentiates anti-tumor effect of resveratrol on pancreatic cancer by
      down-regulation of VEGF-B signaling pathway.
AB  - Our previous study showed that resveratrol (RSV) exhibited not only anti-tumor
      effect, but also had potential tumor promotion effect on pancreatic cancer (Paca)
      cells through up-regulation of VEGF-B. We determined whether metformin (MET)
      could potentiate the anti-tumor effect of RSV on PaCa in this study. Combination
      of RSV (100 MUmol/l) and MET (20 mmol/l) significantly inhibited tumor growth and
      increased apoptosis of human PaCa in comparison with RSV or MET alone treatment
      in PaCa cell lines (Miapaca-2, Panc-1 and Capan-2). Combination of RSV (60 mg/kg,
      gavage) and MET (250 mg/kg, i.p.) significantly inhibited tumor growth in PaCa
      bearing nude mice (subcutaneous injection of 5 * 106 Miapaca-2 cells) in
      comparison with RSV or MET alone treatment on day 40. Combination treatment
      significantly decreased VEGF-B expression and inhibited activity of GSK-3beta
      when compared to the RSV alone treatment. Up-regulated expressions of Bax,
      cleaved caspase-3 and down-regulated expression of Bcl-2 were observed in RSV+
      MET group in comparison with RSV group either in vitro or in vivo. Inhibition of
      VEGF-B by VEGF-B small interfering RNA (siRNA) mimicked the effects of MET on
      PaCa cells. These results suggested that MET, a potential pharmacological
      inhibitor of VEGF-B signaling pathway, potentiated the anti-tumor effect of RSV
      on PaCa, and combination of MET and RSV would be a promising modality for
      clinical PaCa therapy.

PMID- 27705938
TI  - Inhibition of autophagy inhibits the conversion of cardiac fibroblasts to cardiac
      myofibroblasts.
AB  - The incidence of heart failure with concomitant cardiac fibrosis is very high in
      developed countries. Fibroblast activation in heart is causal to cardiac fibrosis
      as they convert to hypersynthetic cardiac myofibroblasts. There is no known
      treatment for cardiac fibrosis. Myofibroblasts contribute to the inappropriate
      remodeling of the myocardial interstitium, which leads to reduced cardiac
      function and ultimately heart failure. Elevated levels of autophagy have been
      linked to stress-induced ventricular remodeling and other cardiac diseases.
      Previously, we had shown that TGF-beta1 treatment of human atrial fibroblasts
      both induced autophagy and enhanced the fibrogenic response supporting a linkage
      between the myofibroblast phenotype and autophagy. We now demonstrate that with
      in vitro culture of primary rat cardiac fibroblasts, inhibition of autophagy
      represses fibroblast to myofibroblast phenoconversion. Culturing unpassaged
      cardiac fibroblasts for 72 hours on plastic tissue culture plates is associated
      with elevated alpha-smooth muscle actin (alpha-SMA) expression. This activation
      parallels increased microtubule-associated protein 1A/1B-light chain 3 (LC-3beta
      II) protein expression. Inhibition of autophagy with bafilomycin-A1 (Baf-A1) and
      chloroquine (CQ) in cardiac fibroblasts significantly reduces alpha-SMA and
      extracellular domain A fibronectin (ED-A FN) protein vs untreated controls.
      Myofibroblast cell migration and contractility were significantly reduced
      following inhibition of autophagy. These data support the possibility of a causal
      link between cardiac fibroblast-to-myofibroblast phenoconversion and autophagy.

PMID- 27705939
TI  - The andean anticancer herbal product BIRM causes destabilization of androgen
      receptor and induces caspase-8 mediated-apoptosis in prostate cancer.
AB  - BIRM is an anticancer herbal formulation from Ecuador. Previous study established
      its antitumor and antimetastatic activity against prostate cancer models. The
      activity of BIRM against human prostate cancer (PCa) cells was investigated to
      uncover its mechanism of antitumor activity. In androgen receptor (AR)-expressing
      PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT)
      compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and
      LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased
      apoptosis. Exposing cells to BIRM did not affect the synthesis of AR and AR
      promoter activity but increased degradation of AR via proteasome-pathway. BIRM
      caused destabilization of HSP90-AR association in LAPC-4 cells. It induced
      apoptosis in PCa cells by activation of caspase-8 via death receptor and FADD
      mediated pathways. A synthetic inhibitor of Caspase-8 cleavage (IETD-CHO) aborted
      BIRM-induced apoptosis. The effect of BIRM on AKT-mediated survival pathway in
      both AR+ and AR- negative (PC-3 and DU145) showed decreased levels of p-AKTser
      473 in all PCa cell lines. BIRM dosed by oral gavage in mice bearing PC-3ML
      tumors showed selective efficacy on tumor growth; before tumors are established
      but limited efficacy when treated on existing tumors. Moreover, BIRM inhibited
      the LNCaP tumor generated by orthotropic implantation into dorsal prostate of
      nude mice. Partial purification of BIRM by liquid-liquid extraction and further
      fractionation by HPLC showed 4-fold increased specific activity on PCa cells.
      These results demonstrate a mechanistic basis of anti-tumor activity of the
      herbal extract BIRM.

PMID- 27705940
TI  - Combined targeting of SET and tyrosine kinases provides an effective therapeutic
      approach in human T-cell acute lymphoblastic leukemia.
AB  - Recent evidence suggests that inhibition of protein phosphatase 2A (PP2A) tumor
      suppressor activity via the SET oncoprotein contributes to the pathogenesis of
      various cancers. Here we demonstrate that both SET and c-MYC expression are
      frequently elevated in T-ALL cell lines and primary samples compared to healthy T
      cells. Treatment of T-ALL cells with the SET antagonist OP449 restored the
      activity of PP2A and reduced SET interaction with the PP2A catalytic subunit,
      resulting in a decrease in cell viability and c-MYC expression in a dose
      dependent manner. Since a tight balance between phosphatases and kinases is
      required for the growth of both normal and malignant cells, we sought to identify
      a kinase inhibitor that would synergize with SET antagonism. We tested various T
      ALL cell lines against a small-molecule inhibitor screen of 66 compounds
      targeting two-thirds of the tyrosine kinome and found that combined treatment of
      T-ALL cells with dovitinib, an orally active multi-targeted small-molecule
      receptor tyrosine kinase inhibitor, and OP449 synergistically reduced the
      viability of all tested T-ALL cell lines. Mechanistically, combined treatment
      with OP449 and dovitinib decreased total and phospho c-MYC levels and reduced
      ERK1/2, AKT, and p70S6 kinase activity in both NOTCH-dependent and independent T
      ALL cell lines. Overall, these results suggest that combined targeting of
      tyrosine kinases and activation of serine/threonine phosphatases may offer novel
      therapeutic strategies for the treatment of T-ALL.

PMID- 27705941
TI  - MicroRNA-22 negatively regulates poly(I:C)-triggered type I interferon and
      inflammatory cytokine production via targeting mitochondrial antiviral signaling
      protein (MAVS).
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in
      regulating the host immune response. Here we found that miR-22 is induced in
      glial cells upon stimulation with poly(I:C). Overexpression of miR-22 in the
      cultured cells resulted in decreased activity of interferon regulatory factor-3
      and nuclear factor-kappa B, which in turn led to reduced expression of interferon
      beta and inflammatory cytokines, including tumor necrosis factor-alpha,
      interleukin-1beta, interleukin-6, and chemokine (C-C motif) ligand 5, upon
      stimulation with poly(I:C), whereas knockdown of miR-22 had the opposite effect.
      We used a combination of bioinformatics and experimental techniques to
      demonstrate that mitochondrial antiviral signaling protein (MAVS), which
      positively regulates type I interferon production, is a novel target of miR-22.
      Overexpression of miR-22 decreased the activity of a luciferase reporter
      containing the MAVS 3'-untranslated region and led to decreased MAVS mRNA and
      protein levels. In contrast, ectopic expression of miR-22 inhibitor led to
      elevated MAVS expression. Collectively, our results demonstrate that miR-22
      negatively regulates poly(I:C)-induced production of type I interferon and
      inflammatory cytokines via targeting MAVS.

PMID- 27705942
TI  - RND3 promotes Snail 1 protein degradation and inhibits glioblastoma cell
      migration and invasion.
AB  - Activation of Snail1 signaling promotes the migration and invasion of multiple
      tumors, including glioblastoma multiforme (GBM). However, the molecular mechanism
      that augments Snail1 signaling during GBM cell migration and invasion remains
      largely unknown. Identification of the factors that regulate Snail1 signaling is
      critical to block tumor cell migration and invasion. By screening human GBM
      specimens, we found that the expression levels of small GTPase RND3 positively
      correlated with the expression levels of E-cadherin and claudin, the glioblastoma
      migration biomarkers negatively regulated by Snail1. Downregulation of E-cadherin
      and claudin has been associated with the migration and invasion of GBM cells. We
      demonstrated that RND3 functioned as an endogenous inhibitor of the Snail
      directed transcriptional regulation. RND3 physically interacted with Snail1
      protein, enhanced Snail1 ubiquitination, and facilitated the protein degradation.
      Forced expression of RND3 inhibited Snail1 activity, which in turn blocked
      glioblastoma cell migration and invasion in vitro in cell culture and in vivo in
      GBM xenograft mice. In contrast, downregulation of RND3 augmented Snail1
      activity, and subsequently decreased E-cadherin expression, eventually promoted
      glioblastoma cell migration and invasion. The pro-migration induced by RND3
      downregulation was attenuated by Snail1 knockdown. The findings partially explain
      why Snail1 activity is augmented in GBM, and defines a new function of RND3 in
      GBM cell migration and invasion.

PMID- 27705943
TI  - Copy number gain of VCX, X-linked multi-copy gene, leads to cell proliferation
      and apoptosis during spermatogenesis.
AB  - Male factor infertility affects one-sixth of couples worldwide, and non
      obstructive azoospermia (NOA) is one of the most severe forms. In recent years
      there has been increasing evidence to implicate the participation of X chromosome
      in the process of spermatogenesis. To uncover the roles of X-linked multi-copy
      genes in spermatogenesis, we performed systematic analysis of X-linked gene copy
      number variations (CNVs) and Y chromosome haplogrouping in 447 idiopathic NOA
      patients and 485 healthy controls. Interestingly, the frequency of individuals
      with abnormal level copy of Variable charge, X-linked (VCX) was significantly
      different between cases and controls after multiple test correction (p = 5.10 *
      10-5). To discriminate the effect of gain/loss copies in these genes, we analyzed
      the frequency of X-linked multi-copy genes in subjects among subdivided groups.
      Our results demonstrated that individuals with increased copy numbers of Nuclear
      RNA export factor 2 (NXF2) (p = 9.21 * 10-8) and VCX (p = 1.97 * 10-4) conferred
      the risk of NOA. In vitro analysis demonstrated that increasing copy number of
      VCX could upregulate the gene expression and regulate cell proliferation and
      apoptosis. Our study establishes a robust association between the VCX CNVs and
      NOA risk.

PMID- 27705944
TI  - Analysis of angiogenesis related factors in glioblastoma, peritumoral tissue and
      their derived cancer stem cells.
AB  - The formation of new blood vessels represents a crucial event under both
      physiological and pathological circumstances. In this study, we evaluated by
      immunohistochemistry, and/or Western blotting and/or quantitative real time-PCR
      the expression of HIF1alpha, HIF2alpha, VEGF, VEGFR1 and VEGFR2 in surgical
      glioblastoma multiforme (GBM) and peritumoral tissue samples obtained from 50
      patients as well as in cancer stem cells (CSCs) isolated from GBM (GCSCs) and
      peritumoral tissue (PCSCs) of 5 patients. We also investigated the contribution
      of both GCSCs and PCSCs on the behavior of endothelial cells (ECs) in vitro.
      Immunohistochemistry demonstrated the expression of angiogenesis markers in both
      GBM and peritumoral tissue. In addition, in vitro tube formation assay indicated
      that both GCSCs and PCSCs stimulate EC proliferation as well as tube-like vessel
      formation. An increased migration aptitude was mainly observed when ECs were
      cultured in the presence of GCSCs rather than in the presence of PCSCs. These
      findings suggest that relevant neoangiogenetic events may occur in GBM. In
      particular, VEGF/VEGFR co-expression in PCSCs leads to hypothesize the
      involvement of an autocrine signaling. Moreover, our results suggest that both
      GCSCs and PCSCs own the skill of activating the "angiogenic switch" and the
      capability of modulating EC behavior, indicating that both cell types are either
      responsive to angiogenic stimuli or able to trigger angiogenic response. Together
      with our previous findings, this study adds a further piece to the challenging
      puzzle of the characterization of peritumoral tissue and of the definition of its
      real role in GBM pathophysiology.

PMID- 27705945
TI  - Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV
      infection on the risk of cervical precancerous lesions in Chinese population.
AB  - Human papillomavirus (HPV) infection is a definite risk factor for cervical
      cancer. Nevertheless, only some infected individuals actually develop cervical
      cancer. The cGAS-STING pathway in innate immunity plays an important role in
      protecting against HPV infection. Chen et al. described that the rs2516448 SNP in
      the MHC locus may affect susceptibility to cervical cancer, a finding that we
      attempted to replicate in a Chinese population. To investigate the effects of
      cGAS, STING and MHC polymorphisms on susceptibility to cervical precancerous
      lesions, 9 SNPs were analyzed in 164 cervical precancerous lesion cases and 428
      controls. Gene-gene and gene-environment interactions were also evaluated. We
      found a significantly decreased risk of cervical precancerous lesions for the GG
      genotype of rs311678 in the cGAS gene (ORadjusted = 0.40, 95% CI: 0.16-0.98).
      Moreover, MDR analysis identified a significant three-locus interaction model,
      involving HPV infection, age at menarche and rs311678 in cGAS. Additionally, a
      significant antagonistic interaction between HPV infection and rs311678 was found
      on an additive scale. In conclusion, our results indicate that the rs311678
      polymorphism in the cGAS gene confers genetic susceptibility to cervical
      precancerous lesions. Moreover, the three-way gene-environment interactions
      further demonstrate that the rs311678 polymorphism in cGAS can significantly
      decrease the risk of HPV infection and the elder at menarche.

PMID- 27705946
TI  - Necessity of organized low-dose computed tomography screening for lung cancer:
      From epidemiologic comparisons between China and the Western nations.
AB  - OBJECTIVES: To compare the proportion of stage I lung cancer and population
      mortality in China to those in U.S. and Europe where lung cancer screening by low
      dose computed tomography (LDCT) has been already well practiced. METHODS: The
      proportions of stage I lung cancer in LDCT screening population in U.S. and
      Europe were retrieved from NLST and NELSON trials. The general proportion of
      stage I lung cancer in China was retrieved from a rapid meta-analysis, based on a
      literature search in the China National Knowledge Infrastructure database. The
      lung cancer mortality and prevalence of China, U.S. and Europe was retrieved from
      Globocan 2012 fact sheet. Mortality-to-prevalence ratio (MPR) was applied to
      compare the population survival outcome of lung cancer. RESULTS: The estimated
      proportion of stage I lung cancer in China is merely 20.8% among hospital-based
      cross-sectional population, with relative ratios (RRs) being 2.40 (95% CI 2.18
      2.65) and 2.98 (95% CI 2.62-3.38) compared by LDCT-screening population in U.S.
      and Europe trials, respectively. MPR of lung cancer is as high as 58.9% in China,
      with RRs being 0.46 (95% CI 0.31-0.67) and 0.58 (95% CI 0.39-0.85) compared by
      U.S. and Europe, respectively. CONCLUSIONS: By the epidemiological inference, the
      LDCT mass screening might be associated with increasing stage I lung cancer and
      therefore improving population survival outcome. How to translate the experiences
      of lung cancer screening by LDCT from developed counties to China in a cost
      effective manner needs to be further investigated.

PMID- 27705947
TI  - MiRNA203 suppresses the expression of protumorigenic STAT1 in glioblastoma to
      inhibit tumorigenesis.
AB  - MicroRNAs (miRNAs) play critical roles in regulating cancer cell proliferation,
      migration, survival and sensitivity to chemotherapy. The potential application of
      using miRNAs for cancer prognosis holds great promise but miRNAs with predictive
      value remain to be identified and underlying mechanisms of how they promote or
      suppress tumorigenesis are not completely understood. Here, we show a strong
      correlation between miR203 expression and brain cancer patient survival. Low
      miR203 expression is found in subsets of brain cancer patients, especially
      glioblastoma. Ectopic miR203 expression in glioblastoma cell lines inhibited cell
      proliferation and migration, increased sensitivity to apoptosis induced by
      interferon or temozolomide in vitro, and inhibited tumorigenesis in vivo. We
      further show that STAT1 is a direct functional target of miR203, and miR203 level
      is negatively correlated with STAT1 expression in brain cancer patients.
      Knockdown of STAT1 expression mimicked the effect of overexpression of miR203 in
      glioblastoma cell lines, and inhibited cell proliferation and migration,
      increased sensitivity to apoptosis induced by IFN or temozolomide in vitro, and
      inhibited glioblastoma tumorigenesis in vivo. High STAT1 expression significantly
      correlated with poor survival in brain cancer patients. Mechanistically, we found
      that enforced miR203 expression in glioblastoma suppressed STAT1 expression
      directly, as well as that of a number of STAT1 regulated genes. Taken together,
      our data suggest that miR203 acts as a tumor suppressor in glioblastoma by
      suppressing the pro-tumorigenic action of STAT1. MiR203 may serve as a predictive
      biomarker and potential therapeutic target in subsets of cancer patients with low
      miR203 expression.

PMID- 27705948
TI  - Survival prediction in patients undergoing radionuclide therapy based on
      intratumoral somatostatin-receptor heterogeneity.
AB  - The NETTER-1 trial demonstrated significantly improved progression-free survival
      (PFS) for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors
      (NET) emphasizing the high demand for response prediction in appropriate
      candidates. In this multicenter study, we aimed to elucidate the prognostic value
      of tumor heterogeneity as assessed by somatostatin receptor (SSTR)-PET/CT. 141
      patients with SSTR-expressing tumors were analyzed obtaining SSTR-PET/CT before
      PRRT (1-6 cycles, 177Lu somatostatin analog). Using the Interview Fusion
      Workstation (Mediso), a total of 872 metastases were manually segmented.
      Conventional PET parameters as well as textural features representing
      intratumoral heterogeneity were computed. The prognostic ability for PFS and
      overall survival (OS) were examined. After performing Cox regression, independent
      parameters were determined by ROC analysis to obtain cut-off values to be used
      for Kaplan-Meier analysis. Within follow-up (median, 43.1 months), 75 patients
      showed disease progression (median, 22.2 m) and 54 patients died (median, 27.6
      m). Cox analysis identified 8 statistically independent heterogeneity parameters
      for time-to-progression and time-to-death. Among them, the textural feature
      Entropy predicted both PFS and OS. Conventional PET parameters failed in response
      prediction. Imaging-based heterogeneity assessment provides prognostic
      information in PRRT candidates and outperformed conventional PET parameters. Its
      implementation in clinical practice can pave the way for individualized patient
      management.

PMID- 27705949
TI  - Age-related decline in cardiac autonomic function is not attenuated with
      increased physical activity.
AB  - Age and physical inactivity are important risk factors for cardiovascular
      mortality. Heart rate response to exercise (HRRE) and heart rate recovery (HRR),
      measures of cardiac autonomic function, are strong predictors of mortality. The
      present study defined the effect of age and physical activity on HRRE and HRR.
      Healthy women (N=72) grouped according to age (young, 20-30 years; middle, 40-50
      years; and older, 65-81 years) and daily physical activity (low active <7500,
      high active >12,500 steps/day) performed a maximal cardiopulmonary exercise test.
      The HRRE was defined as an increase in heart rate from rest to 1, 3 and 5 minutes
      of exercise and at 1/3 of total exercise time, and HRR as the difference in heart
      rate between peak exercise and 1, 2, and 3 minutes later. Age was associated with
      a significant decline in HRRE at 1 min and 1/3 of exercise time (r=-0.27, p=0.04,
      and r=-0.39, p=0.02) and HRR at 2 min and 3 min (r=-0.35, p=0.01, and r=-0.31,
      p=0.02). There was no significant difference in HRRE and HRR between high and low
      active middle-age and older women (p>0.05). Increased level of habitual physical
      activity level appears to have a limited effect on age-related decline in cardiac
      autonomic function in women.

PMID- 27705951
TI  - Electrical and thermal transport properties of the electron-doped cuprate Sm2-x
      Ce x CuO4-y system.
AB  - Electrical and thermal transport measurements were performed on thin films of the
      electron-doped superconductor Sm2-x Ce x CuO4-y (x  =  0.13  -  0.19) in order to
      study the evolving nature of the charge carriers from the under-doped to over
      doped regime. A temperature versus cerium content (T  -  x) phase diagram has
      been constructed from the electrical transport measurements, yielding a
      superconducting region similar to that found for other electron-doped
      superconductors. Thermopower measurements show a dramatic change from the
      underdoped region (x  <  0.15) to the overdoped region (x  >  0.15). Application
      of the Fisher-Fisher-Huse (FFH) vortex glass scaling model to the
      magnetoresistance data was found to be insufficient to describe the data in the
      region of the vortex-solid to vortex-liquid transition. It was found instead that
      the modified vortex glass scaling model of Rydh, Rapp, and Anderson provided a
      good description of the data, indicating the importance of the applied field on
      the pinning landscape. A magnetic field versus temperature (H  -  T) phase
      diagram has also been constructed for the films with [Formula: see text],
      displaying the evolution of the vortex glass melting lines H g (T) across the
      superconducting regime.

PMID- 27705950
TI  - Evolution of renal function in African patients initiating second-line
      antiretroviral treatment: findings from the ANRS 12169 2LADY trial.
AB  - BACKGROUND: To investigate change in renal function in African patients
      initiating second-line antiretroviral therapy (ART) including ritonavir-boosted
      protease inhibitor (PI/r) with or without tenofovir disoproxil fumarate (TDF).
      METHODS: HIV-1-positive adults, failing standard first-line ART were randomized
      to either TDF/emtricitabine (FTC)+LPV/r, abacavir + didanosine +LPV/r or TDF/FTC+
      darunavir (DRV)/r and followed for 18 months. Patients with an estimated
      glomerular filtration rate (eGFR) >=60 ml/min/1.73 m2 at baseline were included
      in this analysis. RESULTS: Data from 438 out of 454 randomized patients were
      analysed. Median age was 38 years and 72% were women. Initiation of PI/r-based
      second-line regimen induced a marked eGFR decline of -10.5 ml/min/1.73 m2 at week
      4 in all treatment groups with a greater decrease in TDF/FTC+LPV/r arm (-15.1
      ml/min/1.73 m2). At month 18, mean eGFR in the non-TDF containing regimen
      recovered its baseline level and was significantly greater than eGFR 18-month
      levels in the TDF-containing regimens that experienced only partial recovery
      (difference: -10.7; CI -16.8, -4.6; P=0.001 in TDF/FTC+LPV/r and -6.4; CI -12.5, 
      0.3; P=0.04 in TDF/FTC+DRV/r). At 18 months, prevalence of stage 3 chronic kidney
      disease was low (<3%) and not associated with treatment. One treatment
      discontinuation and five TDF dosage reductions for renal toxicities were reported
      in TDF-containing arms. CONCLUSIONS: Overall, these results suggest a reasonable
      renal tolerance of a regimen associating TDF/FTC+PI/r in African patients with
      eGFR>60 ml/ml/1.73 m2 at baseline. They also support the recommendation of
      reassessing renal function 1 month after initiation of treatment including
      ritonavir to account for the ritonavir-related artefactual decrease of eGFR and
      determine the new reference baseline value.

PMID- 27705953
TI  - The Coulomb-interaction-induced breaking of the Aufbau principle for the hole
      charging of InGaAs/GaAs quantum dots.
AB  - The so called 'incomplete hole shell filling' phenomenon, that is the breaking of
      the Aufbau principle was reported by Reuter et al (Phys. Rev. Lett. 94 026808) in
      the hole charging spectra of a quantum dot when the results were interpreted in
      the context of the s/p/d shell system-typical for electrons. We report an example
      of an inter-particle-interaction induced Aufbau principle violation even if it is
      applied to the one-particle Kohn-Luttinger eigenstates. We present a [Formula:
      see text]/configuration-interaction study that concerns multiple holes confined
      in an InGaAs/GaAs self-assembled cylindrical quantum dot. The eigenenergies and
      eigenvectors of up to six hole ground states were obtained-along with the
      corresponding one-hole orbital occupations-and discussed in the context of the
      Aufbau principle.

PMID- 27705952
TI  - Fast detection of covert visuospatial attention using hybrid N2pc and SSVEP
      features.
AB  - OBJECTIVE: Detecting the shift of covert visuospatial attention (CVSA) is vital
      for gaze-independent brain-computer interfaces (BCIs), which might be the only
      communication approach for severely disabled patients who cannot move their eyes.
      Although previous studies had demonstrated that it is feasible to use CVSA
      related electroencephalography (EEG) features to control a BCI system, the
      communication speed remains very low. This study aims to improve the speed and
      accuracy of CVSA detection by fusing EEG features of N2pc and steady-state visual
      evoked potential (SSVEP). APPROACH: A new paradigm was designed to code the left
      and right CVSA with the N2pc and SSVEP features, which were then decoded by a
      classification strategy based on canonical correlation analysis. Eleven subjects
      were recruited to perform an offline experiment in this study. Temporal waves,
      amplitudes, and topographies for brain responses related to N2pc and SSVEP were
      analyzed. The classification accuracy derived from the hybrid EEG features (SSVEP
      and N2pc) was compared with those using the single EEG features (SSVEP or N2pc).
      MAIN RESULTS: The N2pc could be significantly enhanced under certain conditions
      of SSVEP modulations. The hybrid EEG features achieved significantly higher
      accuracy than the single features. It obtained an average accuracy of 72.9% by
      using a data length of 400 ms after the attention shift. Moreover, the average
      accuracy reached ~80% (peak values above 90%) when using 2 s long data.
      SIGNIFICANCE: The results indicate that the combination of N2pc and SSVEP is
      effective for fast detection of CVSA. The proposed method could be a promising
      approach for implementing a gaze-independent BCI.

PMID- 27705954
TI  - Raman spectroscopy of K x Co2-y Se2 single crystals near the ferromagnet
      paramagnet transition.
AB  - Polarized Raman scattering spectra of the K x Co2-y Se2 single crystals reveal
      the presence of two phonon modes, assigned as of the A 1g and B 1g symmetry. The
      absence of additional modes excludes the possibility of vacancy ordering, unlike
      in K x Fe2-y Se2. The ferromagnetic (FM) phase transition at [Formula: see text]
      K leaves a clear fingerprint on the temperature dependence of the Raman mode
      energy and linewidth. For [Formula: see text] the temperature dependence looks
      conventional, driven by the thermal expansion and anharmonicity. The Raman modes
      are rather broad due to the electron-phonon coupling increased by the disorder
      and spin fluctuation effects. In the FM phase the phonon frequency of both modes
      increases, while an opposite trend is seen in their linewidth: the A 1g mode
      narrows in the FM phase, whereas the B 1g mode broadens. We argue that the large
      asymmetry and anomalous frequency shift of the B 1g mode is due to the coupling
      of spin fluctuations and vibration. Our density functional theory (DFT)
      calculations for the phonon frequencies agree rather well with the Raman
      measurements, with some discrepancy being expected since the DFT calculations
      neglect the spin fluctuations.

PMID- 27705955
TI  - Changing head model extent affects finite element predictions of transcranial
      direct current stimulation distributions.
AB  - OBJECTIVE: In this study, we determined efficient head model sizes relative to
      predicted current densities in transcranial direct current stimulation (tDCS).
      APPROACH: Efficiency measures were defined based on a finite element (FE)
      simulations performed using nine human head models derived from a single MRI data
      set, having extents varying from 60%-100% of the original axial range. Eleven
      tissue types, including anisotropic white matter, and three electrode montages
      (T7-T8, F3-right supraorbital, Cz-Oz) were used in the models. MAIN RESULTS:
      Reducing head volume extent from 100% to 60%, that is, varying the model's axial
      range from between the apex and C3 vertebra to one encompassing only apex to the
      superior cerebellum, was found to decrease the total modeling time by up to half.
      Differences between current density predictions in each model were quantified by
      using a relative difference measure (RDM). Our simulation results showed that
      [Formula: see text] was the least affected (a maximum of 10% error) for head
      volumes modeled from the apex to the base of the skull (60%-75% volume).
      SIGNIFICANCE: This finding suggested that the bone could act as a bioelectricity
      boundary and thus performing FE simulations of tDCS on the human head with models
      extending beyond the inferior skull may not be necessary in most cases to obtain
      reasonable precision in current density results.

PMID- 27705956
TI  - Using the detectability index to predict P300 speller performance.
AB  - OBJECTIVE: The P300 speller is a popular brain-computer interface (BCI) system
      that has been investigated as a potential communication alternative for
      individuals with severe neuromuscular limitations. To achieve acceptable accuracy
      levels for communication, the system requires repeated data measurements in a
      given signal condition to enhance the signal-to-noise ratio of elicited brain
      responses. These elicited brain responses, which are used as control signals, are
      embedded in noisy electroencephalography (EEG) data. The discriminability between
      target and non-target EEG responses defines a user's performance with the system.
      A previous P300 speller model has been proposed to estimate system accuracy given
      a certain amount of data collection. However, the approach was limited to a
      static stopping algorithm, i.e. averaging over a fixed number of measurements,
      and the row-column paradigm. A generalized method that is also applicable to
      dynamic stopping (DS) algorithms and other stimulus paradigms is desirable.
      APPROACH: We developed a new probabilistic model-based approach to predicting BCI
      performance, where performance functions can be derived analytically or via Monte
      Carlo methods. Within this framework, we introduce a new model for the P300
      speller with the Bayesian DS algorithm, by simplifying a multi-hypothesis to a
      binary hypothesis problem using the likelihood ratio test. Under a normality
      assumption, the performance functions for the Bayesian algorithm can be
      parameterized with the detectability index, a measure which quantifies the
      discriminability between target and non-target EEG responses. MAIN RESULTS:
      Simulations with synthetic and empirical data provided initial verification of
      the proposed method of estimating performance with Bayesian DS using the
      detectability index. Analysis of results from previous online studies validated
      the proposed method. SIGNIFICANCE: The proposed method could serve as a useful
      tool to initially assess BCI performance without extensive online testing, in
      order to estimate the amount of data required to achieve a desired accuracy
      level.

PMID- 27705957
TI  - Interface mixing and its impact on exchange coupling in exchange biased systems.
AB  - Exchange bias and interlayer exchange coupling are interface driven phenomena.
      Since an ideal interface is very challenging to achieve, a clear understanding of
      the chemical and magnetic natures of interfaces is pivotal to identify their
      influence on the magnetism. We have chosen Ni80Fe20/CoO(t CoO)/Co trilayers as a
      model system, and identified non-stoichiometric Ni-ferrite and Co-ferrite at the
      surface and interface, respectively. These ferrites, being ferrimagnets
      typically, should influence the exchange coupling. However, in our trilayers the
      interface ferrites were found not to be ferro- or ferri-magnetic; thus having no
      observable influence on the exchange coupling. Our analysis also revealed that
      (i) interlayer exchange coupling was present between Ni80Fe20 and Co even though
      the interlayer thickness was significantly larger than expected for this
      phenomenon to happen, and (ii) the majority of the CoO layer (except some portion
      near the interface) did not contribute to the observed exchange bias. We also
      identified that the interlayer exchange coupling and the exchange bias properties
      were not interdependent.

PMID- 27705959
TI  - Neural mechanisms underlying catastrophic failure in human-machine interaction
      during aerial navigation.
AB  - OBJECTIVE: We investigated the neural correlates of workload buildup in a fine
      visuomotor task called the boundary avoidance task (BAT). The BAT has been known
      to induce naturally occurring failures of human-machine coupling in high
      performance aircraft that can potentially lead to a crash-these failures are
      termed pilot induced oscillations (PIOs). APPROACH: We recorded EEG and
      pupillometry data from human subjects engaged in a flight BAT simulated within a
      virtual 3D environment. MAIN RESULTS: We find that workload buildup in a BAT can
      be successfully decoded from oscillatory features in the electroencephalogram
      (EEG). Information in delta, theta, alpha, beta, and gamma spectral bands of the
      EEG all contribute to successful decoding, however gamma band activity with a
      lateralized somatosensory topography has the highest contribution, while theta
      band activity with a fronto-central topography has the most robust contribution
      in terms of real-world usability. We show that the output of the spectral decoder
      can be used to predict PIO susceptibility. We also find that workload buildup in
      the task induces pupil dilation, the magnitude of which is significantly
      correlated with the magnitude of the decoded EEG signals. These results suggest
      that PIOs may result from the dysregulation of cortical networks such as the
      locus coeruleus (LC)-anterior cingulate cortex (ACC) circuit. SIGNIFICANCE: Our
      findings may generalize to similar control failures in other cases of tight man
      machine coupling where gains and latencies in the control system must be inferred
      and compensated for by the human operators. A closed-loop intervention using
      neurophysiological decoding of workload buildup that targets the LC-ACC circuit
      may positively impact operator performance in such situations.

PMID- 27705960
TI  - Biorthogonal projected energies of a Gutzwiller similarity transformed
      Hamiltonian.
AB  - We present a method incorporating biorthogonal orbital-optimization, symmetry
      projection, and double-occupancy screening with a non-unitary similarity
      transformation generated by the Gutzwiller factor [Formula: see text], and apply
      it to the Hubbard model. Energies are calculated with mean-field computational
      scaling with high-quality results comparable to coupled cluster singles and
      doubles. This builds on previous work performing similarity transformations with
      more general, two-body Jastrow-style correlators. The theory is tested on 2D
      lattices ranging from small systems into the thermodynamic limit and is compared
      to available reference data.

PMID- 27705958
TI  - Chronic in vivo stability assessment of carbon fiber microelectrode arrays.
AB  - OBJECTIVE: Individual carbon fiber microelectrodes can record unit activity in
      both acute and semi-chronic (~1 month) implants. Additionally, new methods have
      been developed to insert a 16 channel array of carbon fiber microelectrodes.
      Before assessing the in vivo long-term viability of these arrays, accelerated
      soak tests were carried out to determine the most stable site coating material.
      Next, a multi-animal, multi-month, chronic implantation study was carried out
      with carbon fiber microelectrode arrays and silicon electrodes. APPROACH: Carbon
      fibers were first functionalized with one of two different formulations of PEDOT
      and subjected to accelerated aging in a heated water bath. After determining the
      best PEDOT formula to use, carbon fiber arrays were chronically implanted in rat
      motor cortex. Some rodents were also implanted with a single silicon electrode,
      while others received both. At the end of the study a subset of animals were
      perfused and the brain tissue sliced. Tissue sections were stained for
      astrocytes, microglia, and neurons. The local reactive responses were assessed
      using qualitative and quantitative methods. MAIN RESULTS: Electrophysiology
      recordings showed the carbon fibers detecting unit activity for at least 3 months
      with average amplitudes of ~200 MUV. Histology analysis showed the carbon fiber
      arrays with a minimal to non-existent glial scarring response with no adverse
      effects on neuronal density. Silicon electrodes showed large glial scarring that
      impacted neuronal counts. SIGNIFICANCE: This study has validated the use of
      carbon fiber microelectrode arrays as a chronic neural recording technology.
      These electrodes have demonstrated the ability to detect single units with high
      amplitude over 3 months, and show the potential to record for even longer
      periods. In addition, the minimal reactive response should hold stable
      indefinitely, as any response by the immune system may reach a steady state after
      12 weeks.

PMID- 27705962
TI  - Asymptotic behavior of impurity-induced bound states in low-dimensional
      topological superconductors.
AB  - We study theoretically the asymptotic behavior of the Shiba bound states
      associated with magnetic impurities embedded in both 2D and 1D anomalous
      superconductors. We calculate analytically the spatial dependence of the local
      density of states together with the spin polarization associated with the Shiba
      bound states. We show that the latter quantity exhibits drastic differences
      between s-wave and different types of p-wave superconductors. Such properties,
      which could be measured using spin-polarized STM, offer therefore a way to
      discriminate between singlet and triplet pairing in low-dimensional
      superconductors, as well as a way to estimate the amplitude of the triplet
      pairing in these systems.

PMID- 27705961
TI  - Muscle-tendon units localization and activation level analysis based on high
      density surface EMG array and NMF algorithm.
AB  - OBJECTIVE: Some skeletal muscles can be subdivided into smaller segments called
      muscle-tendon units (MTUs). The purpose of this paper is to propose a framework
      to locate the active region of the corresponding MTUs within a single skeletal
      muscle and to analyze the activation level varieties of different MTUs during a
      dynamic motion task. APPROACH: Biceps brachii and gastrocnemius were selected as
      targeted muscles and three dynamic motion tasks were designed and studied. Eight
      healthy male subjects participated in the data collection experiments, and 128
      channel surface electromyographic (sEMG) signals were collected with a high
      density sEMG electrode grid (a grid consists of 8 rows and 16 columns). Then the
      sEMG envelopes matrix was factorized into a matrix of weighting vectors and a
      matrix of time-varying coefficients by nonnegative matrix factorization
      algorithm. MAIN RESULTS: The experimental results demonstrated that the
      weightings vectors, which represent invariant pattern of muscle activity across
      all channels, could be used to estimate the location of MTUs and the time-varying
      coefficients could be used to depict the variation of MTUs activation level
      during dynamic motion task. SIGNIFICANCE: The proposed method provides one way to
      analyze in-depth the functional state of MTUs during dynamic tasks and thus can
      be employed on multiple noteworthy sEMG-based applications such as muscle force
      estimation, muscle fatigue research and the control of myoelectric prostheses.

PMID- 27705963
TI  - Identifying auditory attention with ear-EEG: cEEGrid versus high-density cap-EEG
      comparison.
AB  - OBJECTIVE: This study presents a direct comparison of a classical EEG cap setup
      with a new around-the-ear electrode array (cEEGrid) to gain a better
      understanding of the potential of ear-centered EEG. APPROACH: Concurrent EEG was
      recorded from a classical scalp EEG cap and two cEEGrids that were placed around
      the left and the right ear. Twenty participants performed a spatial auditory
      attention task in which three sound streams were presented simultaneously. The
      sound streams were three seconds long and differed in the direction of origin
      (front, left, right) and the number of beats (3, 4, 5 respectively), as well as
      the timbre and pitch. The participants had to attend to either the left or the
      right sound stream. MAIN RESULTS: We found clear attention modulated ERP effects
      reflecting the attended sound stream for both electrode setups, which agreed in
      morphology and effect size. A single-trial template matching classification
      showed that the direction of attention could be decoded significantly above
      chance (50%) for at least 16 out of 20 participants for both systems. The
      comparably high classification results of the single trial analysis underline the
      quality of the signal recorded with the cEEGrids. SIGNIFICANCE: These findings
      are further evidence for the feasibility of around the-ear EEG recordings and
      demonstrate that well described ERPs can be measured. We conclude that concealed
      behind-the-ear EEG recordings can be an alternative to classical cap EEG
      acquisition for auditory attention monitoring.

PMID- 27705964
TI  - Interaction with the MAPT H1H1 Genotype Increases Dementia Risk in APOE epsilon4
      Carriers in a Population of Southern India.
AB  - BACKGROUND: This study delineates the role of the interaction of apolipoprotein E
      (APOE) and MAPT alleles in contributing to disease risks of dementia in a
      southern Indian population. METHODS: A sample of 419 patients comprising
      Alzheimer's disease (AD; n = 156), mild cognitive impairment (MCI; n = 87),
      frontotemporal dementia (FTD; n = 127), vascular dementia (VD; n = 37), and
      dementia with Lewy bodies (DLB; n = 12) was analysed in comparison with a control
      group (n = 138). APOE genotyping and MAPT haplotyping were performed on all study
      subjects. RESULTS: Multivariate logistic regression analysis showed that
      variability on the APOE locus influenced the relative risk of dementia in the
      study population. The APOE epsilon4 allele increased the disease risk most
      significantly for AD (OR = 3.468, p < 0.0001) and MCI (OR = 2.901, p < 0.0001).
      The APOE epsilon2 allele remained protective for AD (OR = 0.205, p < 0.05). For
      FTD, VD, and DLB, the APOE epsilon4 allele was ineffectual in modulating disease
      risk. The MAPT H1 haplotype was not an overrepresented marker of
      neurodegenerative diseases. The H1H1 genotype had an additive effect in
      contributing to either disease risk in combination with the APOE epsilon4 allele
      or protection in combination with the APOE epsilon2 or epsilon3 allele.
      CONCLUSIONS: This study is a reappraisal of the strong association of APOE
      variability with AD in southern India when compared to other dementia groups,
      while the transcriptional differences between MAPT haplotypes have a limited role
      in Indian dementia patients.

PMID- 27705965
TI  - High Prognostic Value of Mini-Laparoscopy for Advanced Liver Disease-Related
      Complications in Patients with HCV Infection.
AB  - BACKGROUND/AIM: The assessment of advanced chronic liver disease (ACLD) is a
      prerequisite for therapy and surveillance in patients with chronic hepatitis C
      infection. Mini-laparoscopy-assisted liver biopsies facilitate both histological
      and macroscopical evaluation of liver fibrosis. This study is aimed at
      investigating the prognostic significance of the laparoscopic assessment for the
      cumulative incidence of ACLD-related events. PATIENTS AND METHODS: We performed a
      single center, retrospective analysis of 94 patients with either macroscopically
      or/and microscopically assessed advanced fibrosis/cirrhosis caused by chronic
      hepatitis C infection. The patients' data, the respective laboratory results, and
      follow-up period were evaluated in the outpatient clinic. RESULTS: The group with
      both macro- and microscopic diagnosed ACLD showed a significantly higher number
      of decompensating events (n = 7) compared with the other 2 groups (n = 0 in the
      group with only histological and n = 1 in the group with only laparoscopic
      diagnosis of advanced liver disease). The results were not affected by the
      successful treatment of the hepatitis C virus. In the Cox-regression analysis,
      the spleen size (>120 mm) was significantly associated with the incidence of ACLD
      related events. CONCLUSIONS: Assessment of ACLD in chronic hepatitis C by mini
      laparoscopy-assisted liver biopsies may facilitate the selection of patients with
      a poor prognosis, irrespective of achieving a sustained virological response
      following treatment. Follow-up of these patients should be intensified to treat
      decompensation early.

PMID- 27705967
TI  - Evaluating the Utility of a 'N-of-1' Precision Cancer Medicine Strategy: The Case
      for 'Time-to-Subsequent-Disease Progression'.
AB  - It is increasingly recognized that cancer is a highly heterogeneous group of
      illnesses even within a particular organ site (e.g., breast, lung, colon, etc.).
      This observation presents a serious challenge to the traditional concept of phase
      3 randomized trials designed to define therapeutic efficacy of a novel treatment
      strategy. For while 10% of the patients with a common malignancy (e.g., non-small
      cell lung cancer) may be sufficient to consider such an effort, enrolling a
      sufficient number of patients into a clinical trial in a timely manner to define
      clinical utility would be extremely difficult if the population in question
      represented only 1% of this population, and essentially impossible if one wished
      to explore the benefits of treatment in a rarer neoplasm (e.g. ovarian cancer).
      Therefore, in the new era of precision cancer medicine, alternative research
      designs are imperative. One option would be to compare the time-to-disease
      progression of an individual cancer patient following treatment with a novel
      therapeutic to the time-to-disease progression for that specific patient on
      her/his immediately preceding treatment. The rationale for this strategy and
      early experience with this innovative approach to evaluating the efficacy of
      anticancer therapy is highlighted in this report.

PMID- 27705966
TI  - Prolonged Treatment of Peanut-Allergic Mice with Bortezomib Significantly Reduces
      Serum Anti-Peanut IgE but Does Not Affect Allergic Symptoms.
AB  - BACKGROUND: Anti-peanut immunoglobulin E (anti-Pn IgE) can persist throughout
      life, suggesting that this condition could be maintained by long-lived antibody
      secreting cells (ASCs). To determine the role of long-lived ASCs, peanut-allergic
      mice underwent prolonged treatment with the proteasome inhibitor, bortezomib
      (Bz). METHODS: Intravenous Bz was given twice weekly for 21 weeks to peanut
      allergic mice. During treatment, serum anti-Pn IgE was measured, and the mice
      were rechallenged at the end of treatment. Cell populations were measured, and Pn
      specific IgG, total IgG, and total IgE ASCs were enumerated in the bone marrow
      (BM) and spleen (SPL). RESULTS: Prolonged treatment with Bz significantly reduced
      serum anti-Pn IgE and IgG1 but did not affect symptoms following challenge with
      Pn, even in mice with undetectable serum anti-Pn IgE. Numbers of CD138+ cells
      were significantly reduced in the BM but were unaffected in the SPL.
      Unexpectedly, Bz did not affect numbers of Pn-specific IgG, total IgG, or total
      IgE ASCs in either the BM or SPL. CONCLUSIONS: Cells that maintain long-lived
      serum anti-Pn IgE are sensitive to Bz. However, prolonged depletion of serum Pn
      specific IgE does not result in a decrease of symptoms following challenge with
      Pn.

PMID- 27705968
TI  - Social Factors Associated with the Decline in Caries in Brazilian Children
      between 1996 and 2010.
AB  - Dental caries levels have declined in children since the 1970s in many countries.
      Most of the postulated main reasons for the decline are speculative and have not
      been rigorously evaluated. The objective of this study was to assess the
      relationship between some social factors and the decline in dental caries in
      Brazilian 12-year-old children from 1996 to 2010. Secondary analysis of national
      data was performed in 27 Brazilian state capitals. A panel data regression model
      with fixed effects and multiple linear regression were used to verify the
      relationship between the explanatory and the dependent variables and also the
      time-trend effect. The results showed that the DMFT (decayed, missing, and filled
      teeth) decreased by about 3% per year, and the percentage of caries-free children
      increased by 4.5% per year. For DMFT and percentage caries free, the results for
      the panel data regression showed a significant association for the Human
      Development Index (HDI) in the adjusted model (p = 0.010). When the overall
      changes over time were compared, the Gini index had a significant association
      with the overall change in DMFT in the final model of the multiple regression
      analysis (p = 0.033). Our results indicate that the maintenance of good levels of
      human development, which includes better education, income, and longevity, are
      important factors relating to improving levels of oral health in 12-year-old
      Brazilian children. However, to accelerate this process in cities with the worst
      caries situation, income inequality should be tackled.

PMID- 27705969
TI  - Non-Invasive Haemodynamic Monitoring in Pregnancy: A Comparative Study Using
      Ultrasound and Bioreactance.
AB  - BACKGROUND: Due to the importance of cardiovascular dysfunction and advances in
      the development and use of non-invasive cardiac output (CO) monitoring devices,
      there is a growing interest in their use in the obstetric population. The aim of
      this study was to compare two commercially available, non-invasive CO monitors in
      the assessment of heart rate (HR), stroke volume (SV), CO, cardiac index (CI) and
      total peripheral resistance (TPR) in an obstetric population. METHODS: This was a
      prospective, comparative study including two groups. A normotensive group, which
      consisted of uncomplicated healthy pregnancies, and a hypertensive group, which
      consisted of those complicated by hypertensive disorders of pregnancy. Non
      invasive cardiovascular assessments were performed using two methodologies.
      USCOM(r) is an operator-dependent Doppler ultrasound device which obtains
      velocity time integrals of transaortic blood flow at the left ventricular outflow
      tract, while NICOM(r) provides an operator-independent haemodynamic profile by
      assessing thoracic voltage changes (bioreactance) which reflect pulsatile blood
      flow in the thorax. Correlation coefficients were derived, and Bland-Altman
      analysis was performed to derive the mean percentage difference (MPD) between the
      devices. RESULTS: 598 women were recruited for this study. In the normotensive
      group, 524 paired results were analysed, while 74 paired results were analysed in
      the hypertensive group. In the normotensive group, we found excellent correlation
      between USCOM(r) and NICOM(r) for HR (r = 0.885, p < 0.05), and moderate
      correlations for SV (r = 0.445, p < 0.05), CO (r = 0.529, p < 0.05), CI (r =
      0.385, p < 0.05) and TPR (r = 0.524, p < 0.05). In the hypertensive group, we
      obtained similar correlations (HR: r = 0.877, p < 0.05; SV: r = 0.575, p < 0.05;
      CO: r = 0.601, p < 0.05; TPR: r = 0.589, p < 0.05). Bland-Altman analysis found
      that the agreement between both methodologies improved as gestation advances,
      with an MPD of 34% for CO estimation in the third trimester of uncomplicated
      pregnancies, and 39% in pregnancies complicated by hypertensive disorders.
      CONCLUSION: Our findings suggest that the two methodologies perform similarly in
      both uncomplicated pregnancies and in pregnancies complicated by hypertensive
      disorders. The study findings do not preclude the use of USCOM(r) and NICOM(r)
      devices in pregnancy, but indicate that these platforms cannot be used
      interchangeably. Our findings demonstrate an improvement in MPD as gestation
      advances and, therefore, questions the validity of previous longitudinal studies
      investigating maternal haemodynamics using these methodologies. Our work also
      highlights the need to construct reference ranges for each device and for
      validation of each methodology against a reference method before their use in
      research or clinical practice.

PMID- 27705970
TI  - Successful in utero Percutaneous Fetoscopic Release of a Wrapped Pleuro-Amniotic
      Shunt around the Fetal Arm: Case Report and Review of the Literature.
AB  - BACKGROUND AND OBJECTIVES: Fetal pleural effusions are either primary or
      secondary to chromosomal or structural fetal abnormalities. In both cases,
      thoraco-amniotic shunts may be indicated to prevent life-threatening
      consequences. In this report, we describe a rare complication of shunts and
      successful in utero management of this complication. We also summarize the prior
      reports of shunt wrapping around fetal limbs and successful prenatal release of
      the shunts. DATA SOURCE: Search including PubMed, MEDLINE and EMBASE databases
      from inception till November 2015 was conducted for cases with shunt entrapment
      around fetal limbs with or without prenatal management. RESULTS: Four cases
      including our case have been reported in the literature with wrapping of shunts
      around fetal limbs. Three of these cases were successfully managed prenatally
      using different interventional and anesthetic techniques. CONCLUSIONS: Prenatal
      shunts could be rarely complicated by wrapping of the shunt around fetal limbs
      with possible serious vascular and neurological consequences. Different
      techniques have been described for prenatal management of this condition. We
      describe a less invasive approach that could be done under local anesthesia in
      suitable cases.

PMID- 27705971
TI  - Low Density Lipoprotein Cholesterol and the Outcome of Acute Ischemic Stroke:
      Results of a Large Hospital-Based Study.
AB  - Studies show inconsistent associations between low-density lipoprotein
      cholesterol (LDL-C) and stroke outcome. We assessed these associations among
      patients with first-ever acute ischemic stroke (AIS) in China. Patients with
      first-ever AIS were categorized into 3 groups: normal LDL, marginally elevated
      LDL and high LDL - according to the LDL-C values on admission. The outcome
      measures that were investigated in each group included mortality, dependence and
      recurrence of vascular events. Patients with high LDL-C had higher mortality
      rates than did those with normal LDL-C at both 12 and 36 months, but this
      difference disappeared after adjustment for covariates. There was no difference
      between groups in mortality at 3 months and dependency or recurrence at 3, 12 or
      36 months. LDL-C level was associated with long-term mortality after stroke, but
      was not an independent prognostic factor.

PMID- 27705972
TI  - Third-Line Chemotherapy with Irinotecan plus 5-Fluorouracil in Caucasian
      Metastatic Gastric Cancer Patients.
AB  - PURPOSE: The aim of this study was to evaluate the activity of the combination of
      5-fluorouracil/folinic acid and irinotecan (FOLFIRI) as third-line chemotherapy
      (CT) in metastatic gastric cancer (mGC) patients pretreated with platinum
      derivatives, fluoropyrimidines, and taxanes. METHODS: We prospectively collected
      data of mGC patients treated with third-line FOLFIRI at our institution from 2009
      to 2014. Eligible patients should be treated with a fluoropyrimidine-platinum
      first-line CT and a subsequent taxane-based second-line CT. FOLFIRI consisted of
      irinotecan 180 mg/m2 and leucovorin 200 mg/m2, followed by 5-fluorouracil 2,800
      mg/m2 (administered as 48-hour i.v. continuous infusion from day 1 to 3), with
      cycles repeated every 2 weeks. Response rate (RR) was evaluated according to
      RECIST version 1.0, while progression-free (PFS) and overall survival (OS) were
      estimated using the Kaplan-Meier method. RESULTS: A total of 33 patients were
      included. The majority (97%) had good performance status (0-1 according to ECOG),
      while median PFS after first-line and second-line CT was 5.2 and 4.4 months,
      respectively. Two patients experienced an objective response (RR: 6%), while 14
      patients achieved disease stabilization (disease control rate: 42%). Median PFS
      and OS from the start of third-line CT were 3.3 and 7.5 months, respectively.
      Hematological and nonhematological grade 3-4 toxicities were uncommon and
      included neutropenia (6.1%), diarrhea (9.1%), vomiting (3%), and asthenia (3%).
      Febrile neutropenia was not reported. CONCLUSIONS: Third-line CT with FOLFIRI may
      be an option in heavily pretreated mGC patients with preserved performance status
      and organ function. This regimen has a favorable safety profile, and signs of
      activity have been observed after standard first- and second-line CT.

PMID- 27705973
TI  - Utility of Three-Dimensional Ultrasonography to Assess the Position of Essure
      Tubal Occlusion Device and Its Complications.
AB  - BACKGROUND: To determine the utility of three-dimensional (3D) sonography to
      control the position of hysteroscopic sterilizing device compared to
      hysterosalpingography (HSG). METHODS: A prospective observational study was
      carried out on 139 patients who underwent hysteroscopic tubal occlusion method
      between February 2012 and May 2013. Patients underwent 3D ultrasound scan to
      control device positioning, and they also underwent HSG as an additional control
      method. Comparison between both methods was carried out. RESULTS: In all, 17
      (12.2%) devices were inserted due to a hydrosalpinx and 122 (87.8%) due to
      sterilization purposes. In 124 (89.2%) cases, sonography correlated completely to
      HSG findings. Sonography-positive predictive value was 89.5% to detect correct
      device positioning. Just 4 (2.8%) patients did not present complete tubal
      occlusion 3 months after device insertion; one of them presented device
      expulsion, 2 of them presented previous hydrosalpinx (tubal occlusion was
      confirmed after 6 months), and the last case rejected to undergo further controls
      but device seem to be effective. CONCLUSIONS: 3D sonography seems to be effective
      for the control of sterilization device positioning, but it also detects
      insertion complications and device migration. Further studies would be required
      to assess our findings and the role of sonography in case of hydrosalpinx.

PMID- 27705974
TI  - Myeloperoxidase Anti-Neutrophil Cytoplasmic Antibody-Positive Interstitial
      Pneumonia Associated with Granulomatosis with Polyangiitis Diagnosed by Surgical
      Lung Biopsy.
AB  - Granulomatosis with polyangiitis (GPA) is a rare systemic vasculitis that often
      involves the lung. However, interstitial pneumonia (IP) is rarely seen in GPA
      patients. We herein report 3 cases of IP associated with GPA diagnosed by
      surgical lung biopsy. High-resolution CT showed uniform subpleural reticular
      opacity with traction bronchiectasis. Biopsies from all 3 patients revealed
      neutrophilic capillaritis, microabscesses with giant cells, and coexisting
      histological findings of usual IP pattern or fibrosing nonspecific IP pattern.
      All 3 patients had elevated levels of serum myeloperoxidase anti-neutrophil
      cytoplasmic antibody (MPO-ANCA), but not proteinase 3-ANCA. We diagnosed GPA and
      treated with corticosteroid and cyclophosphamide. Follow-up CT showed improvement
      of the lesions in all patients. Surgical lung biopsy specimens which revealed GPA
      enabled us to conduct the most suitable therapy. This report indicates the
      importance of surgical lung biopsy for differentiating idiopathic IPs from GPA
      associated IP and suggests a relationship between MPO-ANCA and IP in GPA.

PMID- 27705975
TI  - Frequency and Determinants of Adherence to Oral Anticoagulants in Stroke Patients
      with Atrial Fibrillation in Clinical Practice.
AB  - BACKGROUND: Vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs)
      are beneficial in patients with stroke and atrial fibrillation (AF). However,
      little is known about frequency and determinants of adherence to NOACs/VKAs in
      clinical practice. METHODS: This is a single-center explorative study from the
      Novel Oral Anticoagulants in Stroke Patients (NOACISP)-LONGTERM registry. We
      included consecutive AF-stroke patients treated with NOACs/VKAs and followed up
      for 3-24 months. Adherence was assessed at follow-up using structured interviews
      and quantified as the proportion of prescribed doses taken (PDT). Outcome
      measures were (i) full adherence, (ii) >=95% adherence and (iii) >=80% adherence
      (i.e., PDT 100/>=95/>=80%). To explore determinants of full adherence, we
      compared characteristics of fully and non-fully adherent patients. RESULTS: A
      total of 218 of 251 (86.9%) patients (48% female, mean age 77.9 +/- 9.1 years,
      78% NOACs; 22% VKAs) were eligible for analysis with a median follow-up of 12
      months: fully adherent were 78.4% patients (NOACs 77.1%, VKAs 83.3%, p = 0.35),
      >=95% adherent were 95.4% and >=80% adherent were 97.2%. Fully adherent patients
      took more pills daily (median (interquartile range) 7 (5-10) vs. 6 (4-8), p =
      0.039), had more often previous antithrombotic treatment (70.8 vs. 53.2%, p =
      0.023), caregiver-assisted medication administration (54.2 vs. 19.1%, p < 0.001)
      and functional dependency (32.8 vs. 15%, p = 0.011) than non-fully adherent
      patients. CONCLUSIONS: Full adherence was frequent. Patients naive to
      antithrombotics, taking few pills, which they self-administer, were at the
      highest risk of non-adherence and may benefit most from adherence-enhancing
      interventions.

PMID- 27705976
TI  - Contrast Enhanced CT Scans Should Be Permitted in Peritoneal Dialysis Patients
      When Indicated with Precautions.

PMID- 27705977
TI  - The Prognostic Value of Red Blood Cell Distribution Width in Patients on
      Maintenance Hemodialysis.
AB  - AIMS: To examine the association between red blood cell distribution width (RDW)
      and mortality in hemodialysis (HD) patients. METHODS: Three hundred fifty six
      patients on HD for >3 months were enrolled and followed for 2 years. Patients
      were divided into 2 groups according to the median RDW value. Patient survival
      and risk factors for mortality were investigated. RESULTS: The 2-year survival
      rate was significantly lower in the high-RDW group (>14.9%; log-rank = 10.00, p =
      0.0016). RDW (hazard ratio (HR) 1.34, 95% CI 1.04-1.71, p = 0.021), hemoglobin
      (HR 0.98, 95% CI 0.96-1.00, p = 0.023) and albumin (HR 0.90, 95% CI 0.82-0.99, p
      = 0.026) were independent predictors of mortality. Receiver operating
      characteristic curves of RDW to predict 2-year mortality had an area under the
      curve of 0.6487 (95% CI 0.5714-0.7260). CONCLUSIONS: Abnormal RDW was common in
      HD patients and significantly related with poor outcomes in these patients.

PMID- 27705978
TI  - Correlation or Limits of Agreement? Applying the Bland-Altman Approach to the
      Comparison of Cognitive Screening Instruments.
AB  - BACKGROUND/AIMS: Calculation of correlation coefficients is often undertaken as a
      way of comparing different cognitive screening instruments (CSIs). However, test
      scores may correlate but not agree, and high correlation may mask lack of
      agreement between scores. The aim of this study was to use the methodology of
      Bland and Altman to calculate limits of agreement between the scores of selected
      CSIs and contrast the findings with Pearson's product moment correlation
      coefficients between the test scores of the same instruments. METHODS: Datasets
      from three pragmatic diagnostic accuracy studies which examined the Mini-Mental
      State Examination (MMSE) vs. the Montreal Cognitive Assessment (MoCA), the MMSE
      vs. the Mini-Addenbrooke's Cognitive Examination (M-ACE), and the M-ACE vs. the
      MoCA were analysed to calculate correlation coefficients and limits of agreement
      between test scores. RESULTS: Although test scores were highly correlated (all
      >0.8), calculated limits of agreement were broad (all >10 points), and in one
      case, MMSE vs. M-ACE, was >15 points. CONCLUSION: Correlation is not agreement.
      Highly correlated test scores may conceal broad limits of agreement, consistent
      with the different emphases of different tests with respect to the cognitive
      domains examined. Routine incorporation of limits of agreement into diagnostic
      accuracy studies which compare different tests merits consideration, to enable
      clinicians to judge whether or not their agreement is close.

PMID- 27705980
TI  - ST-Segment Elevation Myocardial Infarction in Dialysis and Renal Transplant
      Patients. How Does It Compare to That in the General Population?

PMID- 27705979
TI  - Functional Expression of an Osmosensitive Cation Channel, Transient Receptor
      Potential Vanilloid 4, in Rat Vestibular Ganglia.
AB  - Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel
      expressed in sensory neurons such as those in the dorsal root and trigeminal
      ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat,
      low osmotic pressure, low pH, and phorbol derivatives such as 4alpha-phorbol
      12,13-didecanoate (4alpha-PDD). We investigated the expression of TRPV4 in rat
      vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from
      VG neuron mRNA using reverse-transcription polymerase chain reaction.
      Furthermore, immunoblotting showed positive expression of TRPV4 protein in VG
      neurons. Immunohistochemistry indicated that TRPV4 was localized predominantly on
      the plasma membrane of VG neurons. Calcium (Ca2+) imaging of VG neurons showed
      that 4alpha-PDD and/or hypotonic stimuli caused an increase in intracellular Ca2+
      concentration ([Ca2+]i) that was almost completely inhibited by ruthenium red, a
      selective antagonist of TRPV channels. Interestingly, a [Ca2+]i increase was
      evoked by both hypotonic stimuli and 4alpha-PDD in approximately 38% of VG
      neurons. These data indicate that TRPV4 is functionally expressed in VG neurons
      as an ion channel and that TRPV4 likely participates in VG neurons for vestibular
      neurotransmission as an osmoreceptor and/or mechanoreceptor.

PMID- 27705981
TI  - National Impact of Maintenance Dialysis or Renal Transplantation on Outcomes
      Following ST Elevation Myocardial Infarction.
AB  - BACKGROUND: Though cardiovascular disease is an important cause of mortality in
      patients with end-stage renal disease, epidemiology of ST-elevation myocardial
      infarction (STEMI) is less well described in this population. METHODS: This study
      included STEMI hospitalizations in patients aged >=20 using Nationwide Inpatient
      Sample Database from 2006 to 2010. Primary outcomes were incidence and trends of
      STEMI hospitalizations based on renal function status. We also looked at
      utilization of revascularization procedures, all-cause-hospital mortality and
      predictors of mortality. RESULTS: Of the estimated 882,447 STEMI
      hospitalizations, 11,383 were on maintenance dialysis and 1,076 had renal
      transplants. The incidence of STEMI was over 7 times in patients on maintenance
      dialysis and 1.73 times in renal transplant recipients compared to the general
      population. This incidence has however declined in those on maintenance dialysis
      (p for trend <0.001) to a greater extent than the general population and patients
      with renal transplant. Utilization of revascularization procedures was lowest in
      patients on maintenance dialysis (51.6 vs. 73.3% in renal transplant recipients
      and 77.0% in general population; p < 0.001) and mortality was highest (21.6 vs.
      10.9 vs. 6.8%; p < 0.001). Being on maintenance dialysis or having a renal
      transplant were both independent predictors of mortality in patients hospitalized
      with STEMI. There was a differential effect of cardiac catheterization on odds of
      mortality with lesser impact in patients on maintenance dialysis. CONCLUSIONS:
      STEMI hospitalizations are more common in patients on maintenance dialysis and
      with renal transplants. The utilization of revascularizations procedures remains
      low and mortality high in these patients.

PMID- 27705982
TI  - The Impact of Team-Based Learning (TBL) on Physician Assistant Students' Academic
      Performance in Gross Anatomy.
AB  - PURPOSE: Changes in medical education have prevented students from conducting
      full cadaveric dissections in gross anatomy. The efficacy of alternative
      educational methods is being explored to augment traditional dissection. METHODS:
      Team-based learning was integrated into the 2014 gross anatomy laboratory for
      physician assistants (PA) and nurse anesthetists. Deidentified data from the 2013
      and 2014 courses were used to assess with t-tests the effect of this addition on
      student academic performance. RESULTS: Students in the 2014 course who
      experienced team-based learning performed significantly better on 75% of written
      and laboratory practical examinations (P < .05). Those mean examination increases
      correlated with a positive shift in final grades. A greater benefit was noted for
      PA students than for nurse anesthetist students. CONCLUSIONS: Team-based learning
      is an effective supplement to cadaveric dissection. Student short-term knowledge
      outcomes improve with the combination of dissection and team-based learning in
      the gross anatomy laboratory.

PMID- 27705984
TI  - Pediatric Acute Respiratory Distress Syndrome: Has Assessing Risk of Mortality
      Become Simpler?

PMID- 27705983
TI  - Outcome Comparison in Children Undergoing Extracorporeal Life Support Initiated
      at a Local Hospital by a Mobile Cardiorespiratory Assistance Unit or at a
      Referral Center.
AB  - PURPOSE: To compare characteristics and outcome in children undergoing
      extracorporeal life support initiated in an extracorporeal life support center or
      at the patient's bedside in a local hospital, by means of a mobile
      cardiorespiratory assistance unit. METHODS: A retrospective study in a single
      PICU during 6 years. Extracorporeal life support was started either in our center
      (control group) or in the local hospital (mobile cardiorespiratory assistance
      unit group). The data collected were demographics, markers of patient's
      preextracorporeal life support condition, and outcome. RESULTS: One hundred
      twenty-six children underwent extracorporeal life support, 105 in the control
      group and 21 in the mobile cardiorespiratory assistance unit group. There was no
      difference between groups in terms of age, weight, or Pediatric Risk of Mortality
      II score. There was a significant difference in organ failure etiology between
      groups, with more respiratory cases in the mobile cardiorespiratory assistance
      unit group (76.2%) and more cardiac surgery cases in the control group (60%; p <
      0.001). The duration of extracorporeal life support was longer in the mobile
      cardiorespiratory assistance unit group than in the control group (10 [1-36] vs 5
      [0-33] d; p = 0.003). PICU length of stay and mortality (60% vs 47.6%; p = 0.294)
      were not significantly different between the two groups. To allow comparison of a
      more homogenous population, a subgroup analysis was performed including only
      respiratory failure patients from the two groups (R-control group [n = 22] and R
      mobile cardiorespiratory assistance unit group [n = 16]). PICU length of stay was
      17 (3-64) days in the R-control group and 23 (1-45) days in the R-mobile
      cardiorespiratory assistance unit group (p = 0.564), and PICU mortality rate was
      54.5% in the R-control group and 43.8% in the R-mobile cardiorespiratory
      assistance unit group (p = 0.511). There was no difference between the R-groups
      for age, weight, Pediatric Risk of Mortality II score, and markers of kidney or
      liver dysfunction, and lactate blood levels. CONCLUSION: Extracorporeal life
      support can be safely initiated at children's bedside in the local hospital and
      then transported to the specialized referral center. Our results support the
      validity of an interregional organization of mobile cardiorespiratory assistance
      unit teams.

PMID- 27705985
TI  - Mechanical Ventilation for Pediatric Acute Respiratory Distress Syndrome: Few
      Known Knowns, Many Unknown Unknowns.

PMID- 27705986
TI  - Another Piece to the Puzzle: "A Riddle Wrapped in a Mystery Inside an Enigma"
      Winston Churchill.

PMID- 27705987
TI  - Together We Are Strong. Collaborative Learning as a Strategy for Implementing a
      New Standard of Care.

PMID- 27705988
TI  - Missing Messages of Clinical Pharmacologic Survey on Inotropic Drug Use in
      Neonatal Critical Care.

PMID- 27705989
TI  - Treatment of Refractory Status Epilepticus in Children: Current Practice and
      Opportunities to Improve Care.

PMID- 27705990
TI  - Critical Care Transport: How Perilous the Trip.

PMID- 27705991
TI  - Going All Out: Regionalizing Extracorporeal Life Support.

PMID- 27705992
TI  - Pediatric Septic Shock in the Emergency Department: Can We Set the Alarm Clock a
      Little Forward?

PMID- 27705993
TI  - Confirming Successful Tracheal Intubation With Ultrasound: Is It In?

PMID- 27705994
TI  - How to Train and Maintain Pediatric Intensivists Updated in Focused Cardiac
      Ultrasound?

PMID- 27705995
TI  - The authors reply.

PMID- 27705996
TI  - Score for Neonatal Acute Physiology-II: Use in Neonates With Congenital
      Diaphragmatic Hernia.

PMID- 27705997
TI  - The authors reply.

PMID- 27705998
TI  - Early Use of Albumin in Children With Extensive Burns: Quantifying Fluid
      Requirement.

PMID- 27705999
TI  - The authors reply.

PMID- 27706000
TI  - Intracranial Pressure: Is It a Threshold or a Measure?

PMID- 27706001
TI  - The authors reply.

PMID- 27706002
TI  - The European curriculum for geriatric emergency medicine.

PMID- 27706003
TI  - The Potential Application of Virtual, Augmented, and Mixed Reality in
      Neurourology.

PMID- 27706004
TI  - Role of 5'-AMP-Activated Protein Kinase Activators in Regulating Nuclear Factor
      Kappa B Signaling.

PMID- 27706005
TI  - Stress Urinary Incontinence in Women With Multiple Sclerosis.
AB  - PURPOSE: To report the prevalence and risk factors of stress urinary incontinence
      (SUI) and the prevalence of intrinsic sphincter deficiency in women with multiple
      sclerosis (MS). METHODS: We conducted a retrospective study. Female patients with
      MS, followed for lower urinary tract symptoms (LUTS) during a 15-year period were
      included. Demographic data, MS history, expanded disability status scale (EDSS)
      score at the urodynamic visit, obstetrical past, birth weight, LUTS, and
      urodynamic findings were collected. SUI was defined as incontinence during cough,
      or any effort. A maximum urethral closure pressure less than 30 cm H2O defined
      intrinsic sphincter deficiency. RESULTS: We included 363 women with a mean age of
      46.7+/-10.8 years and a mean disease duration of 12.9+/-8.7 years. The incidence
      of relapsing remitting MS, a secondary progressive form, and a primary
      progressive form was 60.6%, 32.8%, and 6.6%, respectively. The prevalence of SUI
      was 31.4%. The prevalence of intrinsic sphincter deficiency was 1.4% and 0.8% of
      these patients had a SUI (P=0.300). In a multivariate analysis, women with a SUI
      had significantly higher birth weight (P=0.030), a pelvic organ prolapse
      (P=0.021), urgent urinary incontinence (P=0.006), a lower EDSS score (P=0.019),
      and a weaker containing effort (P<0.001). CONCLUSIONS: The prevalence of SUI in
      women with MS was 31.4%. This symptom could affect the quality of life of women
      with MS.

PMID- 27706006
TI  - Percutaneous Nerve Evaluation Test Versus Staged Test Trials for Sacral
      Neuromodulation: Sensitivity, Specificity, and Predictive Values of Each
      Technique.
AB  - PURPOSE: InterStim device is an U.S. Food and Drug Administration approved
      minimal invasive therapy for sacral neuromodulation for lower urinary tract
      dysfunction. Before InterStim implantation, a trial with the appropriate
      screening tests is required to determine patient therapy eligibility. There are
      two different techniques for patient screening: percutaneous nerve evaluation
      (PNE) test and staged test. Few studies have reported success and failure rates
      for each technique. However, test sensitivity and predictive values of either
      test have not been studied. The aim of our study was to determine the sensitivity
      and specificity of each test and to establish a decision algorithm for the most
      appropriate testing method to be used as a screening test. METHODS: This cross
      sectional study was conducted from August 2009 to February 2012 and included
      patients with lower urinary tract dysfunction who participated in the stimulation
      test trial. Patients underwent PNE as the first stimulation test, while those who
      encountered technical difficulty during PNE or electrode migration underwent
      staged testing. RESULTS: A total of 213 patients, including 172 female and 41
      male subjects, underwent PNE. The patients' diagnoses included refractory
      overactive bladder (47.9%), nonobstructive urinary retention (29.6%), and
      frequency urgency syndrome (22.1%). A total of 202 patients were screened with
      PNE and 10 patients with staged testing. Overall sensitivity of PNE was 87.3%,
      and it was 90% for staged test. PNE specificity was 98.5% as compared to 92.9%
      for staged test. Positive and negative predictive values for PNE were 99% and
      82.1% and for staged test were 90% and 92.9%, respectively. CONCLUSIONS: PNE test
      has high specificity and positive predictive value. We recommend PNE, a simple
      office-based, less expensive procedure as the first option for screening.

PMID- 27706007
TI  - Association Between Overactive Bladder and Polyneuropathy in Diabetic Patients.
AB  - PURPOSE: Diabetes mellitus (DM) is a chronic metabolic disorder that often leads
      to complications. We aimed to correlate two complications of DM, polyneuropathy
      and hyperactive bladder syndrome, using noninvasive measures, such as screening
      tests. METHODS: We included 80 female and 40 male type 2 diabetic patients in
      this prospective study. Diabetic polyneuropathy evaluations were conducted using
      the Douleur Neuropathique 4 Questions (DN4), and overactive bladder (OAB)
      evaluations were performed using the Overactive Bladder Questionnaire (OAB-V8).
      The patients were also evaluated for retinopathy and nephropathy. The diabetic
      male and female patients with or without OAB were chosen and compared for
      microvascular complications (polyneuropathy, retinopathy, and nephropathy).
      RESULTS: There were no significant correlations between OAB and retinopathy as
      well as between OAB and nephropathy among diabetic patients (female patients,
      P>0.05; male patients, P>0.05 ). However, the patients with OAB were
      significantly more likely to develop polyneuropathy (female patients, P<0.05;
      male patients, P<0.05). CONCLUSIONS: In diabetic patients, OAB and diabetic
      peripheral neuropathy are significantly correlated. These correlations were
      demonstrated using short, understandable, valid, and reliable disease-specific
      tests without invasive measures. Using these screening tests, both neurologists
      and urologists can easily diagnose these complications.

PMID- 27706008
TI  - Melatonin's Effect on the Efficacy of Desmopressin in the Treatment of Enuresis.
AB  - PURPOSE: This study aims to evaluate and compare the efficacy of exogenous
      melatonin associated with desmopressin (dDAVP) and dietary recommendations.
      METHODS: A total of 189 patients were enrolled from the Service of Pediatrics,
      Campus Bio-Medico University Hospital of Rome, from January 2013 to June 2015. Of
      the 189 original patients, 153 children, aged between 5 and 14 years (mean age,
      8.7 years) were included in the study. After clinical evaluation and a 3-month
      period of observation without treatment, children were assigned to receive
      treatment in one of 3 groups: group 1, dDAVP at a dose of 120 mcg a day
      (Minirin); group 2, dDAVP at a dose of 120 mcg and dietary recommendations; or
      group 3, dDAVP at a dose of 120 mcg, dietary recommendations, and melatonin at a
      dose of 1 mg a day (Melamil plus). Each patient was treated for 3 months.
      RESULTS: After the 3 months of therapy, a desiderable response was achieved in 30
      of 51 patients (58.82%) treated with dDAVP, 35 of 53 patients (66.04%) treated
      with dDAVP and dietary recommendations, and 35 of 49 patients (71.43%) treated
      with dDAVP, dietary recommendations, and melatonin. CONCLUSIONS: Although not
      statistically significant, the results show that the association between dDAVP
      treatment with dietary recommendations and melatonin could be considered a safe
      and effective treatment of NE. Considering that the statistically insignificant
      results might be due to the small sample size, the study will be continued to
      increase the number of subjects.

PMID- 27706009
TI  - Social, Economic, and Medical Factors Associated With Solifenacin Therapy
      Compliance Among Workers Who Suffer From Lower Urinary Tract Symptoms.
AB  - PURPOSE: The prevalence of hyperactive-type lower urinary tract symptoms is
      45.2%, with shares of overactive bladder (OAB) and urge incontinence (UI)
      symptoms of 10.7% and 8.2%, respectively. We investigated the possible impact of
      a wide range of social, economic, and medical factors on compliance with
      solifenacin treatment in the working population. METHODS: Social, economic, and
      medical factors as well as the Overactive Bladder questionnaire - the OAB-q Short
      Form (OAB-q SF), bladder diaries, and uroflowmetry of 1,038 people who were
      administered solifenacin for a year were gathered from employer documentation.
      RESULTS: Among the subjects, 32% maintained their compliance with solifenacin
      treatment throughout the year. Only 65% of the patients had compliance exceeding
      80%, and 17% of patients had compliance of >=50%, yet less than 80% were still
      taking solifenacin 12 months after the beginning of this experiment. Working
      people whose compliance level was, at least, 80% had reliably higher (P<=0.01)
      average age, annual salary, and treatment efficacy, and a greater treatment
      satisfaction level, as well as a lack of satisfaction with other antimuscarinic
      treatments and higher rate of urge UI diagnosis. The same cohort also featured a
      lower level (P<=0.01) of caffeine abuse and lower share of salary spent
      purchasing solifenacin. CONCLUSIONS: This study has shown that compliance with
      solifenacin treatment is associated with a number of significant medical, social,
      and economic factors. The medical factors included the type of urination
      disorder, severity of incontinence symptoms, presence of side effects, treatment
      efficacy and patients' satisfaction with it, and experience using other
      antimuscarinic treatments. Among the social and economic factors, those with the
      strongest correlation to compliance were patient age, employment in medicine and
      education, annual income level, percentage of solifenacin purchase expenditures,
      and caffeine abuse. Factors with a weaker, but still significant, association
      were gender, employment in the transportation industry, and monthly income level.

PMID- 27706011
TI  - Diagnostic Tool for Assessing Overactive Bladder Symptoms: Could the
      International Prostate Symptom Storage Subscore Replace the Overactive Bladder
      Symptom Score?
AB  - PURPOSE: The goal of this study was to compare the International Prostate Symptom
      Storage Subscore (IPSS-s) and the overactive bladder symptom score (OABSS) as
      tools for assessing the symptoms of overactive bladder (OAB). METHODS: A cross
      sectional study was conducted of a sample of 1,341 patients aged 50 years and
      older with lower urinary tract complaints who had undergone a medical examination
      at one of several centers. For each patient, we reviewed the International
      Prostate Symptom Score and the OABSS. The patients were divided into 2 groups
      according to their IPSS-s result (group 1, score >=6; group 2, score<6) and into
      another 2 groups according to their OABSS diagnosis (group 3, OAB patients; group
      4, non-OAB patients). We determined whether the OABSS varied to a statistically
      significant extent between groups 1 and 2. Furthermore, we evaluated the
      correlation of IPSS-s severity with the OABSS results in group 3, and the OAB
      diagnosis rate was compared between groups 1 and 2. RESULTS: In groups 1 and 2,
      the OABSS results were not found to vary to a statistically significant extent
      (P=0.326). In group 3, no significant correlation was found between IPSS-s
      severity and the OABSS results (P=0.385). In the prevalence analysis, no
      statistically significant difference was found among the groups, and the receiver
      operating characteristic curve showed an area under the curve of 0.474.
      CONCLUSIONS: The results of this cross-sectional analysis suggest that the IPSS-s
      and the OABSS are not significantly correlated. Although both scores are used to
      measure OAB symptoms, the simultaneous use of IPSS-s and OABSS is not warranted.

PMID- 27706010
TI  - Foreign Bodies in the Urinary Bladder and Their Management: A Single-Centre
      Experience From North India.
AB  - PURPOSE: This study was performed to characterise the nature, clinical
      presentation, mode of insertion, and management of intravesical foreign bodies in
      patients treated at our hospital. METHODS: Between January 2008 and December
      2014, 49 patients were treated for intravesical foreign bodies at King George
      Medical University, Lucknow. All records of these patients were retrospectively
      analysed to characterise the nature of the foreign body, each patient's clinical
      presentation, the mode of insertion, and how the case was managed. RESULTS: A
      total of 49 foreign bodies were retrieved from patients' urinary bladders during
      the study period. The patients ranged in age from 11 to 68 years. Thirty-three
      patients presented with complaints of haematuria (67.3%), 29 complained of
      frequency of urination and dysuria (59.1%), and 5 patients reported pelvic pain
      (10.2%). The circumstances of insertion were iatrogenic in 20 cases (40.8%), self
      insertion in 17 cases (34.6%), sexual abuse in 4 cases (8.1%), migration from
      another organ in 4 cases (8.1%), and assault in 4 cases (8.1%). Of the foreign
      bodies, 33 (67.3%) were retrieved by cystoscopy, while transurethral
      cystolitholapaxy was required in 10 patients (20.4%), percutaneous suprapubic
      cystolitholapaxy was performed in 4 patients (8.1%), and holmium laser
      lithotripsy was performed in 2 patients (4.08%). CONCLUSIONS: Foreign bodies
      should always be included in the differential diagnosis when evaluating a patient
      who presents with chronic lower urinary tract symptoms. A large percentage of
      foreign bodies can be retrieved using endoscopic techniques. Open surgical
      removal may be performed in cases where endoscopic techniques are unsuitable or
      have failed.

PMID- 27706012
TI  - Sacral Neuromodulation in Patients With a Cardiac Pacemaker.
AB  - The objective of this study was to describe our experience using sacral
      neuromodulation to treat urinary urgency, frequency, urge incontinence, and
      chronic urinary retention in patients with cardiac pacemakers. With the
      increasingly widespread use of InterStim for bladder function restoration, we are
      seeing more complex patients with multiple comorbidities, including cardiac
      conditions. Herein, we report 3 cases of individuals with cardiac pacemakers who
      underwent InterStim implantation to treat urinary conditions. This study is a
      case series of 3 patients with cardiac pacemakers who underwent sacral
      neuromodulation to treat refractory voiding dysfunction. The initial patient
      screening for InterStim therapy involved percutaneous nerve evaluation (PNE), in
      which a temporary untined lead wire was placed through the S3 foramen. Patients
      who did not respond to PNE proceeded to a staged implant. All patients in this
      study had a greater than 50% improvement of their urinary symptoms during the
      initial trial and underwent placement of the InterStim implantable pulse
      generator (IPG). Postoperative programming was done under electrocardiogram
      monitoring by a cardiologist. No interference was observed between the Inter-
      Stim IPG and the cardiac pacemaker. In this group of patients, sacral
      neuromodulation in the presence of a cardiac pacemaker appears to have been safe.

PMID- 27706014
TI  - Typical Value Ranges and Typical Signal Patterns in the Initial Cough in Patients
      With Neurogenic Bladder: Quality Control in Urodynamic Studies.
AB  - PURPOSE: The goal of this study was to establish typical value ranges (TVRs) and
      to analyze typical signal patterns (TSPs) of the initial cough (cough before
      bladder filling) for quality control in urodynamic studies. METHODS: A total of
      539 urodynamic traces from patients with neurogenic bladder obtained over the
      course of a year were retrospectively reviewed. The TVRs for cough amplitude in
      measurements of the intravesical pressure (Pves), abdominal pressure (Pabd), and
      detrusor pressure (Pdet) during the initial cough were established. We used the
      95% range as a reference range for all parameters. Cough spikes in Pdet were
      described and classified, and the reasons for different patterns of cough spikes
      were established. The quality of all the cystometry traces was checked, and we
      also present remedial actions for inappropriate cough spikes. RESULTS: The cough
      amplitudes in the measurements of Pves and Pabd were similar, with 95% of
      measurements falling within the following ranges: 4-62 cm H2O and 3-70 cm H2O,
      respectively, in supine position and 9-95 cm H2O and 8-98 cm H2O, respectively,
      in sitting position. For Pdet, the cough amplitude ranged from -38 to 25 cm H2O
      in supine position and from -44 to 41 cm H2O in sitting position. The cough
      spikes for Pdet were classified as follows: type I, Pdet pressure exhibited a
      minimal change (<5 cm H2O) during the cough; type II, a monophasic spike (>5 cm
      H2O) was observed for Pdet; and type III, biphasic spikes were observed for Pdet.
      Type I coughs were found to have more high-quality traces (P<0.01). CONCLUSIONS:
      TVRs for the initial cough test among neurogenic patients were established in
      order to provide guidelines for quantitative quality control. The TSPs for the
      initial cough signal were described, and the presence of a high-quality cough
      signal may be recommended as a component of quality control in urodynamic
      measurements.

PMID- 27706013
TI  - The Early Histological Effects of Intravesical Instillation of Platelet-Rich
      Plasma in Cystitis Models.
AB  - PURPOSE: To evaluate the early histological effects of the intravesical
      instillation of platelet-rich plasma (PRP) in rabbit models of interstitial and
      hemorrhagic cystitis. METHODS: Thirty-six rabbits were classified into 6 groups:
      saline (S), S+PRP, hydrochloric acid (HCl), HCl+PRP, cyclophosphamide (CyP), and
      CyP+PRP. At 48 hours after induction, PRP was prepared and intravesically
      administered to the S+PRP, HCl+PRP, and CyP+PRP groups. Bladder sections were
      stained with toluidine blue for mast cell counting and with hematoxylin and eosin
      for histopathology and mitotic index determination. The proliferation index was
      determined by proliferating cell nuclear antigen (PCNA) immunolabeling. The
      nonparametric Mann-Whitney U-test was used for statistical analysis. RESULTS: No
      abnormalities were observed in the S group, whereas increased interstitial edema
      and increased average mitotic and proliferation indices were observed in the
      S+PRP group (P=0.023, P=0.004, and P=0.009, respectively). Intense epithelial
      loss, hemorrhage, and leukocyte infiltration were detected in the HCl and HCl+PRP
      groups, whereas a significantly increased average mitotic index was observed in
      the HCl+PRP group (P=0.002). When compared with its CyP counterpart, a
      significant reduction in hemorrhage and an increase in leukocyte infiltration and
      mitotic index were observed in the CyP+PRP group (P=0.006, P=0.038, and P=0.002,
      respectively). In addition, PCNA staining revealed a significantly increased
      proliferation index in the HCl+PRP and CyP+PRP groups (P=0.032 and P=0.015,
      respectively). CONCLUSIONS: The intravesical instillation of PRP increased the
      mitotic index in the saline and cyclophosphamide groups while decreasing
      macroscopic bleeding.

PMID- 27706015
TI  - Translation and Linguistic Validation of the Korean Version of the "Benefit,
      Satisfaction, and Willingness to Continue" Questionnaire for Patients With
      Overactive Bladder.
AB  - PURPOSE: The goal of this study was to develop a Korean version of the Benefit,
      Satisfaction, and Willingness to Continue (BSW) questionnaire from the original
      version, with subsequent linguistic validation by Korean patients with overactive
      bladder who undergo active treatment by a physician. METHODS: Translation and
      linguistic validation were performed in January 2013. The validation process
      included permission for translation, forward translation, reconciliation,
      backward translation, cognitive debriefing, and proofreading. RESULTS: During the
      forward translation process, the terms or phrases of 'benefit,' 'willingness,'
      "have you had any benefit?," "taking all things into account" were adjusted to be
      more appropriate expressions in the Korean language than those used in the
      original version. During the backward translation process, no changes were made
      in terms of the sematic equivalence. In the cognitive debriefing session, 5
      patients were asked to fill in the answers within 5 minutes; most reported that
      the translated questions were clear and easy to understand. One patient felt the
      questions were a little bit difficult to understand; however, the panel decided
      not to change the expressions because the overall level of comprehension was high
      and the translated terms were accurate enough to convey the meaning of the
      original version of the BSW. CONCLUSIONS: The present study showed a successful
      linguistic validation of the BSW questionnaire. Further studies are needed to
      assess of the psychometric properties of the BSW.

PMID- 27706016
TI  - Abnormal Sensory Protein Expression and Urothelial Dysfunction in Ketamine
      Related Cystitis in Humans.
AB  - PURPOSE: The aim of this study was to analyze patterns of sensory protein
      expression and urothelial dysfunction in ketamine-related cystitis (KC) in
      humans. METHODS: Biopsies of bladder mucosa were performed in 29 KC patients
      during cystoscopy. Then specimens were analyzed for tryptase, zonula occludens-1
      (ZO-1), E-cadherin, and terminal deoxynucleotidyl transferase-mediated dUTP nick
      end-labeling (TUNEL) with immunofluorescence staining and quantification. In
      addition, 10 healthy control bladder specimens were analyzed and compared with
      the KC specimens. Another 16 whole bladder specimens obtained from partial
      cystectomy were also analyzed for the muscarinic receptors M2 and M3, endothelial
      nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), beta-3
      adrenergic receptors (beta3-ARs), and the P2X3 receptor by western blotting. In
      addition, 3 normal control bladder specimens were analyzed and compared with the
      KC specimens. RESULTS: The KC bladder mucosa revealed significantly less
      expression of ZO-1 and E-cadherin, and greater expression of TUNEL and tryptase
      activity than the control samples. The expression of M3 and beta3-AR in the KC
      specimens was significantly greater than in the controls. The expression of iNOS,
      eNOS, M2, and P2X3 was not significantly different between the KC and control
      specimens. CONCLUSIONS: The bladder tissue of KC patients revealed significant
      urothelial dysfunction, which was associated with mast-cell mediated
      inflammation, increased urothelial cell apoptosis, and increased expression of
      the M3 and beta3-AR.

PMID- 27706017
TI  - Application of Virtual, Augmented, and Mixed Reality to Urology.
AB  - Recent developments in virtual, augmented, and mixed reality have introduced a
      considerable number of new devices into the consumer market. This momentum is
      also affecting the medical and health care sector. Although many of the
      theoretical and practical foundations of virtual reality (VR) were already
      researched and experienced in the 1980s, the vastly improved features of
      displays, sensors, interactivity, and computing power currently available in
      devices offer a new field of applications to the medical sector and also to
      urology in particular. The purpose of this review article is to review the extent
      to which VR technology has already influenced certain aspects of medicine, the
      applications that are currently in use in urology, and the future development
      trends that could be expected.

PMID- 27706018
TI  - Controls of Nuclear Factor-Kappa B Signaling Activity by 5'-AMP-Activated Protein
      Kinase Activation With Examples in Human Bladder Cancer Cells.
AB  - Generally, both lipopolysaccharide (LPS)- and hypoxia-induced nuclear factor
      kappa B (NF-kappaB) effects are alleviated through differential posttranslational
      modification of NF-kappaB phosphorylation after pretreatment with 5'-AMP
      activated protein kinase (AMPK) activators such as 5'-aminoimidazole-4
      carboxamide ribonucleotide (AICAR) or the hypoglycemic agent metformin. We found
      that AICAR or metformin acts as a regulator of LPS/NF-kappaB-or hypoxia/NF-kappaB
      mediated cyclooxygenase induction by an AMPK-dependent mechanism with
      interactions between p65-NF-kappaB phosphorylation and acetylation, including in
      a human bladder cancer cell line (T24). In summary, we highlighted the regulatory
      interactions of AMPK activity on NF-kappaB induction, particularly in
      posttranslational phosphorylation and acetylation of NF-kappaB under inflammatory
      conditions or hypoxia environment.

PMID- 27706019
TI  - Antidermatophytic Action of Resorcinol Derivatives: Ultrastructural Evidence of
      the Activity of Phenylethyl Resorcinol against Microsporum gypseum.
AB  - In this work, we evaluated the antidermatophytic activities of three resorcinol
      derivatives that have a history of use in dermo-cosmetic applications to discover
      molecules with multiple dermatological activities (i.e., multi-target drugs),
      thereby reducing the cost and time necessary for new drug development. The
      antidermatophytic activities of the three skin lighteners were evaluated relative
      to the known antifungal drug fluconazole on nine dermatophytes responsible for
      the most common dermatomycoses: Microsporum gypseum, Microsporum canis,
      Trichophyton violaceum, Arthroderma cajetani, Trichophyton mentagrophytes,
      Epidermophyton floccosum, Nannizzia gypsea, Trichophyton rubrum and Trichophyton
      tonsurans. Among the three tested resorcinols, only two showed promising
      properties, with the ability to inhibit the growth of all tested dermatophytes;
      additionally, the IC50 values of these two resorcinols against the nine
      dermatophytes confirmed their good antifungal activity, particularly for
      phenylethyl resorcinol against M. gypseum. Ultrastructural alterations exhibited
      by the fungus were observed using scanning electron microscopy and transmission
      electron microscopy and reflected a dose-dependent response to treatment with the
      activation of defence and self-preservation strategies.

PMID- 27706020
TI  - Berry Fruit Consumption and Metabolic Syndrome.
AB  - Metabolic Syndrome is a cluster of risk factors which often includes central
      obesity, dyslipidemia, insulin resistance, glucose intolerance, hypertension,
      endothelial dysfunction, as well as a pro-inflammatory, pro-oxidant, and pro
      thrombotic environment. This leads to a dramatically increased risk of developing
      type II diabetes mellitus and cardiovascular disease, which is the leading cause
      of death both in the United States and worldwide. Increasing evidence suggests
      that berry fruit consumption has a significant potential in the prevention and
      treatment of most risk factors associated with Metabolic Syndrome and its
      cardiovascular complications in the human population. This is likely due to the
      presence of polyphenols with known antioxidant and anti-inflammatory effects,
      such as anthocyanins and/or phenolic acids. The present review summarizes the
      findings of recent dietary interventions with berry fruits on human subjects with
      or at risk of Metabolic Syndrome. It also discusses the potential role of berries
      as part of a dietary strategy which could greatly reduce the need for
      pharmacotherapy, associated with potentially deleterious side effects and
      constituting a considerable financial burden.

PMID- 27706021
TI  - Correction: Greffeuille, V.; et al. Persistent Inequalities in Child
      Undernutrition in Cambodia from 2000 Until Today. Nutrients 2016, 8, 297.
AB  - We would like to submit the following as a correction to our recently published
      paper [1] because of the use of the wrong cut-off for overweight.[...].

PMID- 27706023
TI  - How Doth the Little Crocodilian: Analyzing the Influence of Environmental
      Viscosity on Feeding Performance of Juvenile Alligator mississippiensis.
AB  - Wetland habitats are used as nursery sites for hatchling and juvenile alligators
      (Alligator mississippiensis), where they utilize prey from aquatic and
      terrestrial settings. However, little is known about how viscosity of the medium
      influences feeding performance. We hypothesized that timing and linear excursion
      feeding kinematic variables would be different for individuals feeding on prey
      above the water compared with the same individuals feeding underwater.
      Individuals were fed immobile fish prey and feeding events were recorded using a
      high speed video camera. Feeding performance was summarized by analyzing three
      feeding kinematic variables (maximum gape, maximum gape velocity, duration of
      feeding bout) and success of strike. Results of a series of paired t-tests
      indicated no significant difference in kinematic variables between feeding events
      above water compared with underwater. Similarity in feeding performance could
      indicate that prey-capture is not altered by environmental viscosity or that
      feeding behavior can mitigate its influence. Behavioral differences were observed
      during feeding events with alligators approaching underwater prey having their
      mouths partially opened versus fully closed when feeding above water. This
      behavior could be an indication of a strategy used to overcome water viscosity.

PMID- 27706022
TI  - The Cluster Variation Method: A Primer for Neuroscientists.
AB  - Effective Brain-Computer Interfaces (BCIs) require that the time-varying
      activation patterns of 2-D neural ensembles be modelled. The cluster variation
      method (CVM) offers a means for the characterization of 2-D local pattern
      distributions. This paper provides neuroscientists and BCI researchers with a CVM
      tutorial that will help them to understand how the CVM statistical thermodynamics
      formulation can model 2-D pattern distributions expressing structural and
      functional dynamics in the brain. The premise is that local-in-time free energy
      minimization works alongside neural connectivity adaptation, supporting the
      development and stabilization of consistent stimulus-specific responsive
      activation patterns. The equilibrium distribution of local patterns, or
      configuration variables, is defined in terms of a single interaction enthalpy
      parameter (h) for the case of an equiprobable distribution of bistate
      (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for
      the case of non-equiprobable distribution) yields equilibrium configuration
      variable values. Modeling 2-D neural activation distribution patterns with the
      representational layer of a computational engine, we can thus correlate
      variational free energy minimization with specific configuration variable
      distributions. The CVM triplet configuration variables also map well to the
      notion of a M = 3 functional motif. This paper addresses the special case of an
      equiprobable unit distribution, for which an analytic solution can be found.

PMID- 27706024
TI  - Modified Aloe Polysaccharide Restores Chronic Stress-Induced Immunosuppression in
      Mice.
AB  - Chronic stress generally experienced in our daily lives; is known to augment
      disease vulnerability by suppressing the host immune system. In the present
      study; the effect of modified Aloe polysaccharide (MAP) on chronic stress-induced
      immunosuppression was studied; this Aloe compound was characterized in our
      earlier study. Mice were orally administered with MAP for 24 days and exposed to
      electric foot shock (EFS; duration; 3 min; interval; 10 s; intensity; 2 mA) for
      17 days. The stress-related immunosuppression and restorative effect of MAP were
      then analyzed by measuring various immunological parameters. MAP treatment
      alleviated lymphoid atrophy and body weight loss. The numbers of lymphocyte
      subsets were significantly normalized in MAP-treated mice. Oral administration of
      MAP also restored the proliferative activities of lymphocytes; ovalbumin (OVA)
      specific T cell proliferation; antibody production; and the cell killing activity
      of cytotoxic T lymphocytes. In summary; oral administration of MAP ameliorated
      chronic EFS stress-induced immunosuppression.

PMID- 27706025
TI  - The Role of PET/CT Molecular Imaging in the Diagnosis of Recurrence and
      Surveillance of Patients Treated for Non-Small Cell Lung Cancer.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality
      worldwide and its prognosis remains poor. Molecular imaging with 18F-FDG PET/CT
      can metabolically characterize the nature of lesions as benign or malignant,
      allowing a better staging at the diagnosis of this kind of patient. This
      advantage can also be applied in the re-staging due to the suspicion of recurrent
      disease. Many patients have a recurrence of the disease, including surgically
      treated patients. In the current context, with new personalized oncological
      treatments, the surveillance for recurrence and its accurate diagnosis are
      crucial to improve their survival. In this paper, we revise the current knowledge
      about the clinical and molecular factors related to the recurrent disease. In the
      context of new, promising, available personalized treatments, the role of
      molecular imaging with PET/CT and 18F-FDG and non-18F-FDG radiotracers in the
      follow-up of NSCLC-treated patients is especially attractive and interesting.

PMID- 27706026
TI  - Dexmedetomidine-Induced Contraction Involves CPI-17 Phosphorylation in Isolated
      Rat Aortas.
AB  - Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist, produces
      vasoconstriction, which leads to transiently increased blood pressure. The goal
      of this study was to investigate specific protein kinases and the associated
      cellular signal pathways responsible for the increased calcium sensitization
      induced by dexmedetomidine in isolated rat aortas, with a particular focus on
      phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17). The
      effect of Y-27632 and chelerythrine on the dexmedetomidine-induced intracellular
      calcium concentration ([Ca2+]i) and tension were assessed using fura-2-loaded
      aortic strips. The effects of rauwolscine, Y-27632, chelerythrine, and ML-7
      hydrochloride on the dexmedetomidine-induced phosphorylation of CPI-17 or of the
      20-kDa regulatory light chain of myosin (MLC20) were investigated in rat aortic
      vascular smooth muscle cells. The effects of rauwolscine, Y-27632, and
      chelerythrine on the membrane translocation of Rho-kinase and protein kinase C
      (PKC) phosphorylation induced by dexmedetomidine were assessed. Y-27632 and
      chelerythrine each reduced the slopes of the [Ca2+]i-tension curves of
      dexmedetomidine-induced contraction, and Y-27632 more strongly reduced these
      slopes than did chelerythrine. Rauwolscine, Y-27632, chelerythrine, and ML-7
      hydrochloride attenuated the dexmedetomidine-induced phosphorylation of CPI-17
      and MLC20. Taken together, these results suggest that dexmedetomidine-induced
      contraction involves calcium sensitization, which appears to be mediated by CPI
      17 phosphorylation via Rho-kinase or PKC.

PMID- 27706027
TI  - The Role of Family in a Dietary Risk Reduction Intervention for Cardiovascular
      Disease.
AB  - Diet is an essential strategy for the prevention of primary and secondary
      cardiovascular disease (CVD) events. The objectives were to examine: how families
      at increased risk of CVD perceived personal risk, their motivations to make
      dietary changes, their understanding of diet, and the influence of other family
      members. Individuals (>18 years) who completed an Australian family-based CVD
      risk reduction program were invited to a semi-structured telephone interview.
      Responses were recorded, transcribed verbatim and analysed using a systematic
      deductive approach with coding derived from key concepts developed as part of the
      interview structure. Seventeen participants from eight families were interviewed
      (aged 18-70 years, 47% male, five with CVD diagnosis). Key themes indicated both
      intrinsic and extrinsic motivations to improve heart health, variations in risk
      perception, recognition of the role diet plays in heart health, and the extent of
      family influences on eating patterns. Discrepancies between perceived and actual
      CVD risk perception impacted on perceived "need" to modify current dietary
      patterns towards heart health recommendations. Therefore, strategies not reliant
      on risk perception are needed to engage those with low risk perception. This
      could involve identifying and accessing the family "ringleader" to influence
      involvement and capitalising on personal accountability to other family members.

PMID- 27706029
TI  - Analysis of Aggregation Delay for Multisource Sensor Data with On-Off Traffic
      Pattern in Wireless Body Area Networks.
AB  - Data aggregation plays an important role to improve the transmission efficiency
      in wireless body area networks (WBANs); however, it inherently induces additional
      aggregation delay. Therefore, the effect of packet aggregation on WBAN
      applications, which are vulnerable to delay, must be analyzed rigorously. In this
      paper, we analyze the packet aggregation delay for multisource sensor data with
      an on-off traffic pattern in WBANs. Considering two operational parameters of the
      aggregation threshold and aggregation timer, we calculate the probability that a
      packet aggregation occurs during a unit time and then derive the average
      aggregation delay in closed-form. The analysis results show that the aggregation
      delay increases as the aggregation timer or aggregation threshold increases, but
      is bounded below a certain level according to the number of active sensors and
      their on-off traffic attribute. This implies that the data aggregation technique
      can maximize the transmission efficiency while satisfying a given delay
      requirement in the WBAN system.

PMID- 27706028
TI  - Lycopene, Lutein and Zeaxanthin May Reduce Faecal Blood, Mucus and Pus but not
      Abdominal Pain in Individuals with Ulcerative Colitis.
AB  - BACKGROUND: The main symptom of ulcerative colitis is diarrhoea, which is often
      accompanied by painful tenesmus and faecal blood and mucus. It sometimes co
      occurs with abdominal pain, fever, feeling of fatigue, loss of appetite and
      weight loss. Some dietary factors have been indicated as important in the
      treatment of ulcerative colitis. The aim of the study was to analyse the
      association between retinoid intake (total vitamin A, retinol, beta-carotene,
      alpha-carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin) and
      ulcerative colitis symptoms (abdominal pain, faecal blood, faecal mucus, faecal
      pus) in individuals with ulcerative colitis in remission. METHODS: Assessment of
      diet was based on self-reported data from each patient's dietary records taken
      over a period of three typical, random days (2 weekdays and 1 day of the
      weekend). RESULTS: A total of 56 individuals with ulcerative colitis in remission
      (19 males and 37 females) were recruited for the study. One in every four
      individuals with ulcerative colitis in remission was characterised as having
      inadequate vitamin A intake. Higher lycopene, lutein and zeaxanthin intakes in
      individuals with ulcerative colitis in remission were associated with lower
      faecal blood, mucus and pus but not with lower incidence of abdominal pain.
      Higher carotene intake in individuals with ulcerative colitis in remission may
      contribute to higher incidence of faecal mucus. CONCLUSIONS: Optimising intake of
      specific retinoids may enhance disease control in individuals with ulcerative
      colitis. Prospective studies, including patient reported and objective outcomes,
      are required to confirm this.

PMID- 27706030
TI  - Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant
      Metabolites.
AB  - Fusarium head blight (FHB), primarily caused by Fusarium graminearum, is a
      devastating disease of wheat. Partial resistance to FHB of several wheat
      cultivars includes specific metabolic responses to inoculation. Previously
      published studies have determined major metabolic changes induced by pathogens in
      resistant and susceptible plants. Functionality of the majority of these
      metabolites in resistance remains unknown. In this work we have made a
      compilation of all metabolites determined as selectively accumulated following
      FHB inoculation in resistant plants. Characteristics, as well as possible
      functions and targets of these metabolites, are investigated using
      cheminformatics approaches with focus on the likelihood of these metabolites
      acting as drug-like molecules against fungal pathogens. Results of computational
      analyses of binding properties of several representative metabolites to homology
      models of fungal proteins are presented. Theoretical analysis highlights the
      possibility for strong inhibitory activity of several metabolites against some
      major proteins in Fusarium graminearum, such as carbonic anhydrases and
      cytochrome P450s. Activity of several of these compounds has been experimentally
      confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties
      of plant metabolites can lead to the development of more resistant wheat
      varieties while showing novel application of cheminformatics approaches in the
      analysis of plant/pathogen interactions.

PMID- 27706031
TI  - Advocating for both Environmental and Clinical Approaches to Control Human
      Strongyloidiasis.
AB  - Strongyloidiasis is an underestimated disease caused by the soil-transmitted
      parasite of the genus Strongyloides. It is prevalent in socioeconomically
      disadvantaged communities and it is estimated that global infection could be as
      high as 370 million people. This paper explores current methods of
      strongyloidiasis treatment, which rely on administration of anthelminthic drugs.
      However these drugs cannot prevent reinfection and drug resistance has already
      been observed in veterinary models. This highlights the need for a combined
      approach for controlling Strongyloides that includes both clinical treatment and
      environmental control methods. Currently, nematicides are widely used to control
      plant parasites. The review suggests that due to the species' similarity and
      similar modes of action, these nematicides could also be used to control animal
      and human parasitic nematodes in the environment.

PMID- 27706033
TI  - Growing and Etching MoS2 on Carbon Nanotube Film for Enhanced Electrochemical
      Performance.
AB  - In this work we directly synthesized molybdenum disulfide (MoS2) nanosheets on
      carbon nanotube film (MoS2@CNT) via a two-step chemical vapor deposition method
      (CVD). By etching the obtained MoS2@CNT into 10% wt HNO3, the morphology of MoS2
      decorated on CNT bundles was modulated, resulting in more catalytic active MoS2
      edges being exposed for significantly enhanced electrochemical performance. Our
      results revealed that an 8 h acid etching sample exhibited the best performance
      for the oxygen evolution reaction, i.e., the current density reached 10 mA/cm2
      under 375 mV over-potential, and the tafel slope was as low as 94 mV/dec. The
      enhanced behavior was mainly originated from the more catalytic sites in MoS2
      induced by the acid etching treatment and the higher conductivity from the
      supporting CNT films. Our study provides a new route to produce two-dimensional
      layers on CNT films with tunable morphology, and thus may open a window for
      exploring its promising applications in the fields of catalytic-, electronic-,
      and electrochemical-related fields.

PMID- 27706034
TI  - Neurodegenerative Diseases: Might Citrus Flavonoids Play a Protective Role?
AB  - Neurodegenerative diseases (ND) result from the gradual and progressive
      degeneration of the structure and function of the central nervous system or the
      peripheral nervous system or both. They are characterized by deterioration of
      neurons and/or myelin sheath, disruption of sensory information transmission and
      loss of movement control. There is no effective treatment for ND, and the drugs
      currently marketed are symptom-oriented, albeit with several side effects. Within
      the past decades, several natural remedies have gained attention as potential
      neuroprotective drugs. Moreover, an increasing number of studies have suggested
      that dietary intake of vegetables and fruits can prevent or delay the onset of
      ND. These properties are mainly due to the presence of polyphenols, an important
      group of phytochemicals that are abundantly present in fruits, vegetables,
      cereals and beverages. The main class of polyphenols is flavonoids, abundant in
      Citrus fruits. Our review is an overview on the scientific literature concerning
      the neuroprotective effects of the Citrus flavonoids in the prevention or
      treatment of ND. This review may be used as scientific basis for the development
      of nutraceuticals, food supplements or complementary and alternative drugs to
      maintain and improve the neurophysiological status.

PMID- 27706032
TI  - Plasma Carotenoids, Tocopherols, and Retinol in the Age-Stratified (35-74 Years)
      General Population: A Cross-Sectional Study in Six European Countries.
AB  - Blood micronutrient status may change with age. We analyzed plasma carotenoids,
      alpha-/gamma-tocopherol, and retinol and their associations with age, demographic
      characteristics, and dietary habits (assessed by a short food frequency
      questionnaire) in a cross-sectional study of 2118 women and men (age-stratified
      from 35 to 74 years) of the general population from six European countries.
      Higher age was associated with lower lycopene and alpha-/beta-carotene and higher
      beta-cryptoxanthin, lutein, zeaxanthin, alpha-/gamma-tocopherol, and retinol
      levels. Significant correlations with age were observed for lycopene (r = 
      0.248), alpha-tocopherol (r = 0.208), alpha-carotene (r = -0.112), and beta
      cryptoxanthin (r = 0.125; all p < 0.001). Age was inversely associated with
      lycopene (-6.5% per five-year age increase) and this association remained in the
      multiple regression model with the significant predictors (covariables) being
      country, season, cholesterol, gender, smoking status, body mass index (BMI
      (kg/m2)), and dietary habits. The positive association of alpha-tocopherol with
      age remained when all covariates including cholesterol and use of vitamin
      supplements were included (1.7% vs. 2.4% per five-year age increase). The
      association of higher beta-cryptoxanthin with higher age was no longer
      statistically significant after adjustment for fruit consumption, whereas the
      inverse association of alpha-carotene with age remained in the fully adjusted
      multivariable model (-4.8% vs. -3.8% per five-year age increase). We conclude
      from our study that age is an independent predictor of plasma lycopene, alpha
      tocopherol, and alpha-carotene.

PMID- 27706036
TI  - Synthesis of a 1-Aryl-2,2-chlorosilyl(phospha)silene Coordinated by an N
      Heterocyclic Carbene.
AB  - Phosphasilenes, P=Si doubly bonded compounds, have received considerable
      attention due to their unique physical and chemical properties. We report on the
      synthesis and structure of a chlorophosphasilene coordinated by an N-heterocyclic
      carbene (NHC), which has the potential of functionalization at the Si-Cl moiety.
      Treatment of a silylphosphine, ArPH-SiCl2RSi (Ar = bulky aryl group, RSi =
      Si(SiMe3)3) with two equivalents of Im-Me4 (1,3,4,5-tetramethylimidazol-2
      ylidene) afforded the corresponding NHC-coordinated phosphasilene, ArP=SiClRSi(Im
      Me4) as a stable compound. Bonding properties of the P=Si bond coordinated to an
      NHC will be discussed on the basis of theoretical calculations.

PMID- 27706035
TI  - Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung
      Cancer.
AB  - The malignant behaviors of solid tumors such as growth, infiltration and
      metastasis are mainly nourished by tumor neovascularization. Thus, anti
      angiogenic therapy is key to controlling tumor progression. Bevacizumab, a
      humanized anti-vascular endothelial growth factor (VEGF) antibody, plus
      chemotherapy or biological therapy can prolong survival for cancer patients, but
      treatment-related mortality is a concern. To improve inhibitory effect and
      decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188,
      which is a beta emitting radionuclide, directly labeled with bevacizumab for
      radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that,
      after 188ReO4- or 188Re-bevacizumab at different concentration for 4 and 24 h, a
      time- and radioactivity does-dependent reduction in cell viability occurred.
      Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group
      compared with controls and other treatment groups. In vivo, tumor volumes in the
      188Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed
      compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic
      effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC
      treatment.

PMID- 27706037
TI  - Quantitative and Qualitative Analysis of Flavonoids and Phenolic Acids in Snow
      Chrysanthemum (Coreopsis tinctoria Nutt.) by HPLC-DAD and UPLC-ESI-QTOF-MS.
AB  - A simple, accurate and reliable high performance liquid chromatography coupled
      with photodiode array detection (HPLC-DAD) method was developed and then
      successfully applied for simultaneous quantitative analysis of eight compounds,
      including chlorogenic acid (1), (R/S)-flavanomarein (2), butin-7-O-beta-d
      glucopyranoside (3), isookanin (4), taxifolin (5), 5,7,3',5'
      tetrahydroxyflavanone-7-O-beta-d-glucopyranoside (6), marein (7) and okanin (8),
      in 23 batches of snow chrysanthemum of different seed provenance and from various
      habitats. The results showed total contents of the eight compounds in the samples
      with seed provenance from Keliyang (Xinjiang, China), are higher than in samples
      from the other five provenances by 52.47%, 15.53%, 19.78%, 21.17% and 5.06%,
      respectively, which demonstrated that provenance has a great influence on the
      constituents in snow chrysanthemum. Meanwhile, an ultra performance liquid
      chromatography coupled with electrospray ionization and quadrupole time-of-flight
      mass spectrometry (UPLC-ESI-QTOF-MS) was also employed to rapidly separate and
      identify flavonoids and phenolic acids in snow chrysanthemum from Keliyang. As a
      result, a total of 30 constituents, including 26 flavonoids and four phenolic
      acids, were identified or tentatively identified based on the exact mass
      information, the fragmentation characteristics, and retention times of eight
      reference standards. This work may provide an efficient approach to
      comprehensively evaluate the quality of snow chrysanthemum.

PMID- 27706039
TI  - A Missile-Borne Angular Velocity Sensor Based on Triaxial Electromagnetic
      Induction Coils.
AB  - Aiming to solve the problem of the limited measuring range for angular motion
      parameters of high-speed rotating projectiles in the field of guidance and
      control, a self-adaptive measurement method for angular motion parameters based
      on the electromagnetic induction principle is proposed. First, a framework with
      type bent "I-shape" is used to design triaxial coils in a mutually orthogonal
      way. Under the condition of high rotational speed of a projectile, the induction
      signal of the projectile moving across a geomagnetic field is acquired by using
      coils. Second, the frequency of the pulse signal is adjusted self-adaptively.
      Angular velocity and angular displacement are calculated in the form of periodic
      pulse counting and pulse accumulation, respectively. Finally, on the basis of
      that principle prototype of the sensor is researched and developed, performance
      of measuring angular motion parameters are tested on the sensor by semi-physical
      and physical simulation experiments, respectively. Experimental results
      demonstrate that the sensor has a wide measuring range of angular velocity from 1
      rps to 100 rps with a measurement error of less than 0.3%, and the angular
      displacement measurement error is lower than 0.2 degrees . The proposed method
      satisfies measurement requirements for high-speed rotating projectiles with an
      extremely high dynamic range of rotational speed and high precision, and has
      definite value to engineering applications in the fields of attitude
      determination and geomagnetic navigation.

PMID- 27706038
TI  - Dimerization of the Vacuolar Receptors AtRMR1 and -2 from Arabidopsis thaliana
      Contributes to Their Localization in the trans-Golgi Network.
AB  - In Arabidopsis thaliana, different types of vacuolar receptors were discovered.
      The AtVSR (Vacuolar Sorting Receptor) receptors are well known to be involved in
      the traffic to lytic vacuole (LV), while few evidences demonstrate the
      involvement of the receptors from AtRMR family (Receptor Membrane RING-H2) in the
      traffic to the protein storage vacuole (PSV). In this study we focused on the
      localization of two members of AtRMR family, AtRMR1 and -2, and on the possible
      interaction between these two receptors in the plant secretory pathway. Our
      experiments with agroinfiltrated Nicotiana benthamiana leaves demonstrated that
      AtRMR1 was localized in the endoplasmic reticulum (ER), while AtRMR2 was targeted
      to the trans-Golgi network (TGN) due to the presence of a cytosolic 23-amino acid
      sequence linker. The fusion of this linker to an equivalent position in AtRMR1
      targeted this receptor to the TGN, instead of the ER. By using a Bimolecular
      Fluorescent Complementation (BiFC) technique and experiments of co-localization,
      we demonstrated that AtRMR2 can make homodimers, and can also interact with
      AtRMR1 forming heterodimers that locate to the TGN. Such interaction studies
      strongly suggest that the transmembrane domain and the few amino acids
      surrounding it, including the sequence linker, are essential for dimerization.
      These results suggest a new model of AtRMR trafficking and dimerization in the
      plant secretory pathway.

PMID- 27706040
TI  - Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Hypertensive Effect of
      Protein Hydrolysate from Actinopyga lecanora (Sea Cucumber) in Rats.
AB  - Food protein hydrolysates are known to exhibit angiotensin converting enzyme
      (ACE) inhibitory properties and can be used as a novel functional food for
      prevention of hypertension. This study evaluated the ACE inhibitory potentials of
      Actinopyga lecanora proteolysate (ALP) in vivo. The pre-fed rats with ALP at
      various doses (200, 400, 800 mg/kg body weight) exhibited a significant (p <=
      0.05) suppression effect after inducing hypertension. To determine the optimum
      effective dose that will produce maximal reduction in blood pressure, ALP at
      three doses was fed to the rats after inducing hypertension. The results showed
      that the 800 mg/kg body weight dose significantly reduced blood pressure without
      noticeable negative physiological effect. In addition, there were no observable
      changes in the rats' heart rate after oral administration of the ALP. It was
      concluded that Actinopyga lecanora proteolysate could potentially be used for the
      development of functional foods and nutraceuticals for prevention and treatment
      of hypertension.

PMID- 27706042
TI  - Data-Gathering Scheme Using AUVs in Large-Scale Underwater Sensor Networks: A
      Multihop Approach.
AB  - In this paper, we propose a data-gathering scheme for hierarchical underwater
      sensor networks, where multiple Autonomous Underwater Vehicles (AUVs) are
      deployed over large-scale coverage areas. The deployed AUVs constitute an
      intermittently connected multihop network through inter-AUV synchronization (in
      this paper, synchronization means an interconnection between nodes for
      communication) for forwarding data to the designated sink. In such a scenario,
      the performance of the multihop communication depends upon the synchronization
      among the vehicles. The mobility parameters of the vehicles vary continuously
      because of the constantly changing underwater currents. The variations in the AUV
      mobility parameters reduce the inter-AUV synchronization frequency contributing
      to delays in the multihop communication. The proposed scheme improves the AUV
      synchronization frequency by permitting neighboring AUVs to share their status
      information via a pre-selected node called an agent-node at the static layer of
      the network. We evaluate the proposed scheme in terms of the AUV synchronization
      frequency, vertical delay (node->AUV), horizontal delay (AUV->AUV), end-to-end
      delay, and the packet loss ratio. Simulation results show that the proposed
      scheme significantly reduces the aforementioned delays without the
      synchronization time-out process employed in conventional works.

PMID- 27706041
TI  - Controlling Properties and Cytotoxicity of Chitosan Nanocapsules by Chemical
      Grafting.
AB  - The tunability of the properties of chitosan-based carriers opens new ways for
      the application of drugs with low water-stability or high adverse effects. In
      this work, the combination of a nanoemulsion with a chitosan hydrogel coating and
      the following poly (ethylene glycol) (PEG) grafting is proven to be a promising
      strategy to obtain a flexible and versatile nanocarrier with an improved
      stability. Thanks to chitosan amino groups, a new easy and reproducible method to
      obtain nanocapsule grafting with PEG has been developed in this work, allowing a
      very good control and tunability of the properties of nanocapsule surface. Two
      different PEG densities of coverage are studied and the nanocapsule systems
      obtained are characterized at all steps of the optimization in terms of diameter,
      Z potential and surface charge (amino group analysis). Results obtained are
      compatible with a conformation of PEG molecules laying adsorbed on nanoparticle
      surface after covalent linking through their amino terminal moiety. An
      improvement in nanocapsule stability in physiological medium is observed with the
      highest PEG coverage density obtained. Cytotoxicity tests also demonstrate that
      grafting with PEG is an effective strategy to modulate the cytotoxicity of
      developed nanocapsules. Such results indicate the suitability of chitosan as
      protective coating for future studies oriented toward drug delivery.

PMID- 27706043
TI  - Compensation of Verdet Constant Temperature Dependence by Crystal Core
      Temperature Measurement.
AB  - Compensation of the temperature dependence of the Verdet constant in a
      polarimetric extrinsic Faraday sensor is of major importance for applying the
      magneto-optical effect to AC current measurements and magnetic field sensing.
      This paper presents a method for compensating the temperature effect on the
      Faraday rotation in a Bi12GeO20 crystal by sensing its optical activity effect on
      the polarization of a light beam. The method measures the temperature of the same
      volume of crystal that effects the beam polarization in a magnetic field or
      current sensing process. This eliminates the effect of temperature difference
      found in other indirect temperature compensation methods, thus allowing more
      accurate temperature compensation for the temperature dependence of the Verdet
      constant. The method does not require additional changes to an existing
      Delta/Sigma configuration and is thus applicable for improving the performance of
      existing sensing devices.

PMID- 27706044
TI  - Detection and Characterization of Circulating Tumor Associated Cells in
      Metastatic Breast Cancer.
AB  - The availability of blood-based diagnostic testing using a non-invasive technique
      holds promise for real-time monitoring of disease progression and treatment
      selection. Circulating tumor cells (CTCs) have been used as a prognostic
      biomarker for the metastatic breast cancer (MBC). The molecular characterization
      of CTCs is fundamental to the phenotypic identification of malignant cells and
      description of the relevant genetic alterations that may change according to
      disease progression and therapy resistance. However, the molecular
      characterization of CTCs remains a challenge because of the rarity and
      heterogeneity of CTCs and technological difficulties in the enrichment, isolation
      and molecular characterization of CTCs. In this pilot study, we evaluated
      circulating tumor associated cells in one blood draw by size exclusion technology
      and cytological analysis. Among 30 prospectively enrolled MBC patients, CTCs,
      circulating tumor cell clusters (CTC clusters), CTCs of epithelial-mesenchymal
      transition (EMT) and cancer associated macrophage-like cells (CAMLs) were
      detected and analyzed. For molecular characterization of CTCs, size-exclusion
      method for CTC enrichment was tested in combination with DEPArrayTM technology,
      which allows the recovery of single CTCs or pools of CTCs as a pure CTC sample
      for mutation analysis. Genomic mutations of TP53 and ESR1 were analyzed by
      targeted sequencing on isolated 7 CTCs from a patient with MBC. The results of
      genomic analysis showed heterozygous TP53 R248W mutation from one single CTC and
      pools of three CTCs, and homozygous TP53 R248W mutation from one single CTC and
      pools of two CTCs. Wild-type ESR1 was detected in the same isolated CTCs. The
      results of this study reveal that size-exclusion method can be used to enrich and
      identify circulating tumor associated cells, and enriched CTCs were characterized
      for genetic alterations in MBC patients, respectively.

PMID- 27706045
TI  - Disease Activity and Conversion into Multiple Sclerosis after Optic Neuritis Is
      Treated with Erythropoietin.
AB  - Changes in cerebral lesion load by magnetic resonance imaging (MRI) in patients
      from a double-blind, placebo-controlled, phase II study on erythropoietin in
      clinically isolated optic neuritis (ClinicalTrials.gov, NCT00355095) were
      analyzed. Therefore, patients with acute optic neuritis were assigned to receive
      either 33,000 IU of recombinant human erythropoietin (IV) daily for three days,
      or a placebo, as an add-on to methylprednisolone. Of 35 patients, we investigated
      changes in cerebral lesion load in MRIs obtained at baseline and at weeks 4, 8,
      and 16. In 5 of the 35 patients, we found conversion into multiple sclerosis (MS)
      based on MRI progression only. These five patients had received the placebo.
      Another five patients showed MRI progression together with relapses. Three of
      these patients had received erythropoietin, and two the placebo. Yet, analyzing
      the change in absolute numbers of periventricular, juxtacortical, and
      infratentorial lesions including gadolinium-enhancing lesions, there were no
      significant differences between the groups. Although effective in terms of
      retinal nerve fiber layer protection, erythropoietin treatment of acute isolated
      optic neuritis did not influence further evolution of MRI lesions in the brain
      when comparing absolute numbers. However, early conversion from clinically
      isolated syndrome to MS assessed by MRI activity seemed to occur more frequently
      in the placebo-treated group.

PMID- 27706046
TI  - Internet-Supported Physical Exercise Training for Persons with Multiple Sclerosis
      A Randomised, Controlled Study.
AB  - Physical exercise is effective in improving functional outcomes in persons with
      multiple sclerosis (pwMS). We evaluated the feasibility and effectiveness of
      internet-based exercise training (e-training) for pwMS on health-related quality
      of life (HrQoL). Secondary outcomes were muscle strength, aerobic capacity, lung
      function, physical activity, and fatigue. This is a randomised, controlled trial
      with a wait-list control group. Data were collected at baseline, after three and
      six months, and analysed using a hybrid linear model. One-hundred twenty-six pwMS
      participated in the home-based aerobic (1*/week) and strength training (2*/week)
      intervention that was supervised and documented via an internet-platform. The
      intervention group received e-training for six months, and the control group
      received e-training after a three months waiting period. Significant differences
      between the groups were only observed for muscle strength (knee flexion (effect
      size ES = 0.3, p = 0.003), knee extension (ES = 0.24, p = 0.015)), peak
      expiratory flow (ES = 0.2, p = 0.039), and sports activity (ES = 0.33, p = 0.001)
      after three months. E-training had no effect on HrQoL but did on muscle strength,
      lung function, and physical activity. It is a promising and feasible approach to
      facilitate large-scale, yet individual, training support.

PMID- 27706048
TI  - Assessment of Data Fusion Algorithms for Earth Observation Change Detection
      Processes.
AB  - In this work a parametric multi-sensor Bayesian data fusion approach and a
      Support Vector Machine (SVM) are used for a Change Detection problem. For this
      purpose two sets of SPOT5-PAN images have been used, which are in turn used for
      Change Detection Indices (CDIs) calculation. For minimizing radiometric
      differences, a methodology based on zonal "invariant features" is suggested. The
      choice of one or the other CDI for a change detection process is a subjective
      task as each CDI is probably more or less sensitive to certain types of changes.
      Likewise, this idea might be employed to create and improve a "change map", which
      can be accomplished by means of the CDI's informational content. For this
      purpose, information metrics such as the Shannon Entropy and "Specific
      Information" have been used to weight the changes and no-changes categories
      contained in a certain CDI and thus introduced in the Bayesian information fusion
      algorithm. Furthermore, the parameters of the probability density functions
      (pdf's) that best fit the involved categories have also been estimated.
      Conversely, these considerations are not necessary for mapping procedures based
      on the discriminant functions of a SVM. This work has confirmed the capabilities
      of probabilistic information fusion procedure under these circumstances.

PMID- 27706047
TI  - Implications of Hypoxia in Breast Cancer Metastasis to Bone.
AB  - Most solid tumors contain regions of hypoxia in which increased cell
      proliferation promotes increased oxygen consumption and the condition is further
      exacerbated as cancer cells become localized far from a functional blood vessel,
      further decreasing the oxygen supply. An important mechanism that promotes cell
      adaptation to hypoxic conditions is the expression of hypoxia-inducible factors
      (HIFs). Hypoxia-inducible factors transcriptionally regulate many genes involved
      in the invasion and metastasis of breast cancer cells. Patients, whose primary
      tumor biopsies show high HIF expression levels, have a greater risk of
      metastasis. The current review will highlight the potential role of hypoxia in
      breast cancer metastasis to the bone by considering the regulation of many steps
      in the metastatic process that include invasion, migration, margination and
      extravasation, as well as homing signals and regulation of the bone
      microenvironment.

PMID- 27706051
TI  - Optimization of Sample Points for Monitoring Arable Land Quality by Simulated
      Annealing while Considering Spatial Variations.
AB  - With China's rapid economic development, the reduction in arable land has emerged
      as one of the most prominent problems in the nation. The long-term dynamic
      monitoring of arable land quality is important for protecting arable land
      resources. An efficient practice is to select optimal sample points while
      obtaining accurate predictions. To this end, the selection of effective points
      from a dense set of soil sample points is an urgent problem. In this study, data
      were collected from Donghai County, Jiangsu Province, China. The number and
      layout of soil sample points are optimized by considering the spatial variations
      in soil properties and by using an improved simulated annealing (SA) algorithm.
      The conclusions are as follows: (1) Optimization results in the retention of more
      sample points in the moderate- and high-variation partitions of the study area;
      (2) The number of optimal sample points obtained with the improved SA algorithm
      is markedly reduced, while the accuracy of the predicted soil properties is
      improved by approximately 5% compared with the raw data; (3) With regard to the
      monitoring of arable land quality, a dense distribution of sample points is
      needed to monitor the granularity.

PMID- 27706050
TI  - Universal Stress Proteins as New Targets for Environmental and Therapeutic
      Interventions of Schistosomiasis.
AB  - In spite of various control measures and eradication methods that have been in
      progress, schistosomiasis still prevails as one of the most prevalent
      debilitating parasitic diseases, typically affecting the poor and the
      underprivileged that are predominantly concentrated in sub-Saharan Africa. The
      parasitic schistosome blood fluke responsible for causing the disease completes
      its complex developmental cycle in two hosts: humans and freshwater snails, where
      they physically undergo gross modifications to endure the different conditions
      associated with each host. Just like any other organism, the worm possesses
      mechanisms that help them respond to environmental insults. It has been
      hypothesized that a special class of proteins known as Universal Stress Proteins
      (USPs) are up-regulated during sudden environmental changes, thus assisting the
      worm to tolerate the unfavourable conditions associated with its developmental
      cycle. The position of praziquantel as the drug of choice against all schistosome
      infections has been deemed vulnerable due to mounting concerns over drug pressure
      and so the need for alternative treatment is now a matter of urgency. Therefore,
      this review seeks to explore the associations and possible roles of USPs in
      schistosomiasis as well as the functioning of these proteins in the
      schistosomulae stage in order to develop new therapeutic interventions against
      this disease.

PMID- 27706049
TI  - Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel
      Subfamily of Scorpion Venom Toxins.
AB  - To date, several families of peptide toxins specifically interacting with ion
      channels in scorpion venom have been described. One of these families comprise
      peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202
      KTxs have been reported, belonging to several subfamilies of KTxs (called alpha,
      beta, gamma, kappa, delta, and lambda-KTxs). Here we report on a previously
      described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out
      an in-depth structure-function analysis combining 3D structure elucidation of
      Ts11 and electrophysiological characterization of the toxin. The Ts11 structure
      is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely
      devoid of the classical secondary structure elements (alpha-helix and/or beta
      strand). This has, to the best of our knowledge, never been described before for
      scorpion toxins and therefore represents a novel, 6th type of structural fold for
      these scorpion peptides. On the basis of their preferred interaction with voltage
      gated K channels, as compared to all the other targets tested, it can be
      postulated that Ts11 is the first member of a new subfamily, designated as
      epsilon-KTx.

PMID- 27706053
TI  - Molecular Electron Density Theory: A Modern View of Reactivity in Organic
      Chemistry.
AB  - A new theory for the study of the reactivity in Organic Chemistry, named
      Molecular Electron Density Theory (MEDT), is proposed herein. MEDT is based on
      the idea that while the electron density distribution at the ground state is
      responsible for physical and chemical molecular properties, as proposed by the
      Density Functional Theory (DFT), the capability for changes in electron density
      is responsible for molecular reactivity. Within MEDT, the reactivity in Organic
      Chemistry is studied through a rigorous quantum chemical analysis of the changes
      of the electron density as well as the energies associated with these changes
      along the reaction path in order to understand experimental outcomes. Studies
      performed using MEDT allow establishing a modern rationalisation and to gain
      insight into molecular mechanisms and reactivity in Organic Chemistry.

PMID- 27706052
TI  - Investigation of Self-Assembly Processes for Chitosan-Based Coagulant-Flocculant
      Systems: A Mini-Review.
AB  - The presence of contaminants in wastewater poses significant challenges to water
      treatment processes and environmental remediation. The use of coagulation
      flocculation represents a facile and efficient way of removing charged particles
      from water. The formation of stable colloidal flocs is necessary for floc
      aggregation and, hence, their subsequent removal. Aggregation occurs when these
      flocs form extended networks through the self-assembly of polyelectrolytes, such
      as the amine-based polysaccharide (chitosan), which form polymer "bridges" in a
      floc network. The aim of this overview is to evaluate how the self-assembly
      process of chitosan and its derivatives is influenced by factors related to the
      morphology of chitosan (flocculant) and the role of the solution conditions in
      the flocculation properties of chitosan and its modified forms. Chitosan has been
      used alone or in conjunction with a salt, such as aluminum sulphate, as an aid
      for the removal of various waterborne contaminants. Modified chitosan relates to
      grafted anionic or cationic groups onto the C-6 hydroxyl group or the amine group
      at C-2 on the glucosamine monomer of chitosan. By varying the parameters, such as
      molecular weight and the degree of deacetylation of chitosan, pH, reaction and
      settling time, dosage and temperature, self-assembly can be further investigated.
      This mini-review places an emphasis on the molecular-level details of the
      flocculation and the self-assembly processes for the marine-based biopolymer,
      chitosan.

PMID- 27706054
TI  - Real-Time Estimation of Satellite-Derived PM2.5 Based on a Semi-Physical
      Geographically Weighted Regression Model.
AB  - The real-time estimation of ambient particulate matter with diameter no greater
      than 2.5 MUm (PM2.5) is currently quite limited in China. A semi-physical
      geographically weighted regression (GWR) model was adopted to estimate PM2.5 mass
      concentrations at national scale using the Aqua Moderate Resolution Imaging
      Spectroradiometer (MODIS) Aerosol Optical Depth product fused by the Dark Target
      (DT) and Deep Blue (DB) algorithms, combined with meteorological parameters. The
      fitting results could explain over 80% of the variability in the corresponding
      PM2.5 mass concentrations, and the estimation tends to overestimate when
      measurement is low and tends to underestimate when measurement is high. Based on
      World Health Organization standards, results indicate that most regions in China
      suffered severe PM2.5 pollution during winter. Seasonal average mass
      concentrations of PM2.5 predicted by the model indicate that residential regions,
      namely Jing-Jin-Ji Region and Central China, were faced with challenge from fine
      particles. Moreover, estimation deviation caused primarily by the spatially
      uneven distribution of monitoring sites and the changes of elevation in a
      relatively small region has been discussed. In summary, real-time PM2.5 was
      estimated effectively by the satellite-based semi-physical GWR model, and the
      results could provide reasonable references for assessing health impacts and
      offer guidance on air quality management in China.

PMID- 27706055
TI  - A Set of 20 New SSR Markers Developed and Evaluated in Mandevilla Lindl.
AB  - Mandevilla is an ornamental crop with a bright future worldwide because of its
      high commercial acceptance and added value. However, as with most ornamental
      species, there are few molecular tools to support cultivar breeding and
      innovation. In this work, we report the development and analysis of 20 new Simple
      Sequence Repeat (SSR) markers in Mandevilla. Microsatellites were isolated from
      two enriched small-insert genomic libraries of Mandevilla * amabilis. The
      diversity parameters estimated after their amplification in a group of 11
      commercial genotypes illustrate the effect of two opposite drifts: the high
      relatedness of cultivars belonging to the same commercial group and the high
      divergence of other cultivars, especially M. * amabilis. Based on their different
      band patterns, six genotypes were uniquely distinguished, and two groups of sport
      mutations remained undistinguishable. The amplification of the SSRs in three wild
      species suggested the existence of unexploited diversity available to be
      introgressed into the commercial pool. This is the first report of available
      microsatellites in Mandevilla. The development process has provided some clues
      concerning the genome structure of the species, and the SSRs obtained will help
      to create new products and to protect existing and upcoming plant innovations.

PMID- 27706056
TI  - Non-Obese Diabetes and Its Associated Factors in an Underdeveloped Area of South
      China, Guangxi.
AB  - BACKGROUND: Little research has been conducted on the prevalence of diabetes
      mellitus in underdeveloped areas in China, especially stratified into obesity and
      non-obese diabetes. The aim of the present study was to investigate the
      prevalence and associated factors of non-obese diabetes in an underdeveloped area
      in South China, Guangxi. METHODS: Data derived from the Chinese Health and
      Nutrition Survey 2010-2012 involved a sample of 3874 adults from Guangxi.
      Questionnaires and oral glucose-tolerance tests were conducted, and fasting and 2
      h glucose levels and serum lipids were measured. Logistic regression analysis was
      performed to assess associated factors for non-obese diabetes. RESULTS: 68.2% and
      62.2% of instances of newly detected diabetes were those of non-obese diabetes
      based on BMI (NODB) and based on WC (NODW), respectively. The male sex, an age
      older than 50 years, lower education, hypertension, and hypertriglyceridemia were
      significantly associated with a higher risk of both NODB and NODW, while some
      associated factors for NODB were found different from those associated with NODW,
      and an interaction effect was found to increase the risk of NODW. CONCLUSIONS:
      Our study indicated that non-obese diabetes was highly prevalent in an
      underdeveloped area of South China. Non-obese diabetes should be considered for
      increased public attention in these areas.

PMID- 27706057
TI  - Firefighters' Physical Activity across Multiple Shifts of Planned Burn Work.
AB  - Little is currently known about the physical activity patterns of workers in
      physically demanding populations. The aims of this study were to (a) quantify
      firefighters' physical activity and sedentary time within (2-h periods) and
      across planned burn shifts; and (b) examine whether firefighters' activity levels
      during one shift or 2-h period was associated with their activity levels in the
      following shift or 2-h period. Thirty-four salaried firefighters (26 men, 8
      women) wore an Actical accelerometer for 28 consecutive days. Time spent
      sedentary (SED) and in light- (LPA), moderate- (MPA) and vigorous-intensity
      physical activity (VPA) were derived using validated cut-points. Multilevel
      analyses (shift, participant) were conducted using generalised linear latent and
      mixed models. Firefighters spent the majority of a planned burn shift (average
      length 10.4 h) or 2-h period engaged in LPA (69% and 70%, respectively). No
      significant associations were observed between SED and physical activity levels
      between consecutive planned burned shifts or 2-h periods. The physical activity
      that a firefighter engaged in during one shift (or 2-h period) did not
      subsequently affect their physical activity levels in the subsequent shift (or 2
      h period). Further research is needed to establish how workers in physically
      demanding populations are able to sustain their activity levels over long periods
      of time.

PMID- 27706058
TI  - Nucleophilic Substitution on 2-Monosubstituted Quinoxalines Giving 2,3
      Disubstituted Quinoxalines: Investigating the Effect of the 2-Substituent.
AB  - An investigation on the effect of substituent at the 2-position of mono
      substituted quinoxalines in the synthesis of di-substituted quinoxaline
      derivatives via nucleophilic substitution reactions, is reported. Di-substituted
      quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and
      amino-alkyl substituents were prepared in moderate to good yields. 2
      Monosubstituted quinoxalines bearing a phenyl and butyl substituent reacted
      readily with alkyl-, aryl-, heteroaryl- and alkynyl- nucluephiles, giving di
      substituted quinoxalines. 2-Monosubstituted quinoxalines bearing an amine and
      alkynyl substituent only reacted with alkyl nucleophiles. Oxidative
      rearomatization to give 2,3-disubstituted quinoxaline products occurred in
      atmospheric O2.

PMID- 27706059
TI  - Real-Time Detection of a Self-Replicating RNA Enzyme.
AB  - A system was developed to detect the self-replication of an RNA enzyme in real
      time. The enzyme is an RNA ligase that undergoes exponential amplification at a
      constant temperature and can be made to operate in a ligand-dependent manner. The
      real-time system is based on a fluorimetric readout that directly couples the
      ligation event to an increase in florescence signal that can be monitored using
      standard instrumentation. The real-time system can also operate entirely with l
      RNA, which is not susceptible to degradation by ribonucleases that are present in
      biological samples. The system is analogous to real-time PCR, but with the
      potential to detect small molecules, proteins, and other targets that can be
      recognized by a suitable aptamer. The ligand-dependent self-replication of RNA
      has potential applications in molecular diagnostics and biosensing that benefit
      from the rapid, precise, and real-time detection of various target molecules.

PMID- 27706060
TI  - SimCP3-An Advanced Homologue of SimCP2 as a Solution-Processed Small Molecular
      Host Material for Blue Phosphorescence Organic Light-Emitting Diodes.
AB  - We have overcome the synthetic difficulty of 9,9',9'',9''',9'''',9'''''
      ((phenylsilanetriyl)tris(benzene-5,3,1-triyl))hexakis(9H-carbazole) (SimCP3) an
      advanced homologue of previously known SimCP2 as a solution-processed, high
      triplet gap energy host material for a blue phosphorescence dopant. A series of
      organic light-emitting diodes based on blue phosphorescence dopant iridium (III)
      bis(4,6-difluorophenylpyridinato)picolate, FIrpic, were fabricated and tested to
      demonstrate the validity of solution-processed SimCP3 in the device fabrication.

PMID- 27706061
TI  - Factors Influencing Health Knowledge and Behaviors among the Elderly in Rural
      China.
AB  - OBJECTIVES: Health knowledge and behaviors are the key elements that ensure high
      quality of health for the elderly. This study explored and determined the
      conditions and factors of health knowledge and behaviors that affect the elderly
      in rural China. METHODS: A cross-sectional research approach and random
      stratified sampling method were used in 12 towns and 48 villages in the Chongqing
      Municipality, Henan, and Zhejiang Provinces in China from June to September 2013.
      The collected data included: (1) socio-demographic characteristics of 1593
      elderly people; (2) accuracy rate on health knowledge of the elderly, which was
      analyzed and compared among the three sample areas by using Chi-square test; and
      (3) mean scores on the health behaviors of the elderly, which were analyzed and
      compared by using analysis of variance (ANOVA). The multiple-linear regression
      method was used to analyze the factors affecting the health knowledge and
      behaviors of the elderly. RESULTS: Significant differences were observed among
      the nine items in the health knowledge questionnaire (p = 0.000 < 0.001). The
      average accuracy rate of the nine items was 57.43%. Significant differences were
      observed among the eleven items on the health behaviors of the elderly in the
      sample rural areas (p = 0.000 < 0.001). Age, economic level, degree of education,
      distance from home to medical institutions and disposable personal income (DPI)
      can affect the scores of the health knowledge and behaviors of the elderly (p =
      0.000 < 0.001). CONCLUSIONS: Lack of health knowledge and poor health behaviors
      are common among the elderly in the sample areas of rural China. This deficiency
      poses a serious threat on the promotion of health conditions and the improvement
      of the level of health quality among the elderly. Different types of access to
      sources of health knowledge should be used to increase health knowledge scores of
      the elderly. Various potential intervening measures should also be adopted to
      improve their health behaviors of elderly people.

PMID- 27706062
TI  - Identifying the Gaps in Practice for Combating Lead in Drinking Water in Hong
      Kong.
AB  - Excessive lead has been found in drinking water in Hong Kong in tests carried out
      in 2015. Investigations have identified that the problem in public rental housing
      estates was caused by the problematic solders used in the plumbing, and
      recommendations on enhancing the quality control system and strengthening the
      relevant water quality standards have been proposed. The cause for the same
      problem happening in other premises where soldering has not been adopted for
      water pipe connections is left unidentified. Considering the unidentified cause
      and the recommendations made, this study aims to identify the gaps in practice
      followed in Hong Kong for safeguarding the water quality of new installations. A
      holistic review of governing ordinances and regulations, products and materials
      used and the testing and commissioning requirements adopted in Hong Kong and
      elsewhere in the world were conducted. Based on international practices and
      parametric analysis, it was found that there are gaps in practices followed in
      Hong Kong, which are directly and indirectly leading to the lead-in-water crisis.
      Recommendations for improvement in the quality control system, and the water
      quality standards including the allowable lead content and leaching limit for
      products and materials and the testing and commissioning requirements on plumbing
      installations have been made. The review and the identified gaps would become
      useful reference for countries in strengthening their relevant water quality
      standards.

PMID- 27706063
TI  - A Potential Mechanism for the Anti-Apoptotic Property of Koumine Involving
      Mitochondrial Pathway in LPS-Mediated RAW 264.7 Macrophages.
AB  - Koumine is a kind of alkaloid extracted from Gelsemium elegans (G. elegans).
      Benth, which has shown promise as an anti-tumor, anxiolytic, and analgesic agent.
      In our present study, the effect of koumine on lipopolysaccharide (LPS)-mediated
      RAW 264.7 cell apoptosis was evaluated. MTT assays showed that koumine obviously
      increased cell viability in LPS-mediated RAW 264.7 macrophages. Preincubation
      with koumine ameliorated LPS-medicated apoptosis by decreasing reactive oxygen
      species (ROS) production, which resulted in a significant decrease in the levels
      of nitric oxide (NO) and inducible nitric oxide synthase (iNOS). In addition,
      koumine-pretreated RAW 264.7 macrophages exhibited reduction of LPS-induced
      levels of TNF-alpha, IL-1beta, and IL-6 mRNA. Furthermore, pretreatment with
      koumine suppressed LPS-mediated p53 activation, loss of mitochondrial membrane
      potential, caspase-3 activation, decrease of Bcl-2 expression, and elevation of
      Bax and caspase-3 expressions, suggesting that koumine might act directly on RAW
      264.7 cells to inhibit LPS-induced apoptosis. It seems as though the mechanism
      that koumine possesses is the anti-apoptotic effect mediated by suppressing
      production of ROS, activation of p53, and mitochondrial apoptotic pathways in RAW
      264 cells. Koumine could potentially serve as a protective effect against LPS
      induced apoptosis.

PMID- 27706064
TI  - Assessment of Atmospheric Algorithms to Retrieve Vegetation in Natural Protected
      Areas Using Multispectral High Resolution Imagery.
AB  - The precise mapping of vegetation covers in semi-arid areas is a complex task as
      this type of environment consists of sparse vegetation mainly composed of small
      shrubs. The launch of high resolution satellites, with additional spectral bands
      and the ability to alter the viewing angle, offers a useful technology to focus
      on this objective. In this context, atmospheric correction is a fundamental step
      in the pre-processing of such remote sensing imagery and, consequently, different
      algorithms have been developed for this purpose over the years. They are commonly
      categorized as imaged-based methods as well as in more advanced physical models
      based on the radiative transfer theory. Despite the relevance of this topic, a
      few comparative studies covering several methods have been carried out using high
      resolution data or which are specifically applied to vegetation covers. In this
      work, the performance of five representative atmospheric correction algorithms
      (DOS, QUAC, FLAASH, ATCOR and 6S) has been assessed, using high resolution
      Worldview-2 imagery and field spectroradiometer data collected simultaneously,
      with the goal of identifying the most appropriate techniques. The study also
      included a detailed analysis of the parameterization influence on the final
      results of the correction, the aerosol model and its optical thickness being
      important parameters to be properly adjusted. The effects of corrections were
      studied in vegetation and soil sites belonging to different protected semi-arid
      ecosystems (high mountain and coastal areas). In summary, the superior
      performance of model-based algorithms, 6S in particular, has been demonstrated,
      achieving reflectance estimations very close to the in-situ measurements (RMSE of
      between 2% and 3%). Finally, an example of the importance of the atmospheric
      correction in the vegetation estimation in these natural areas is presented,
      allowing the robust mapping of species and the analysis of multitemporal
      variations related to the human activity and climate change.

PMID- 27706065
TI  - Construction and Characterization of a Cellulolytic Consortium Enriched from the
      Hindgut of Holotrichia parallela Larvae.
AB  - Degradation of rice straw by cooperative microbial activities is at present the
      most attractive alternative to fuels and provides a basis for biomass conversion.
      The use of microbial consortia in the biodegradation of lignocelluloses could
      reduce problems such as incomplete synergistic enzymes, end-product inhibition,
      and so on. In this study, a cellulolytic microbial consortium was enriched from
      the hindgut of Holotrichia parallela larvae via continuous subcultivation (20
      subcultures in total) under static conditions. The degradation ratio for rice
      straw was about 83.1% after three days of cultivation, indicating its strong
      cellulolytic activity. The diversity analysis results showed that the bacterial
      diversity and richness decreased during the consortium enrichment process, and
      the consortium enrichment process could lead to a significant enrichment of phyla
      Proteobacteria and Spirochaetes, classes Clostridia, Epsilonproteobacteria, and
      Betaproteobacteria, and genera Arcobacter, Treponema, Comamonas, and Clostridium.
      Some of these are well known as typical cellulolytic and hemicellulolytic
      microorganisms. Our results revealed that the microbial consortium identified
      herein is a potential candidate for use in the degradation of waste
      lignocellulosic biomass and further highlights the hindgut of the larvae as a
      reservoir of extensive and specific cellulolytic and hemicellulolytic microbes.

PMID- 27706067
TI  - Amplitude Dispersion Compensation for Damage Detection Using Ultrasonic Guided
      Waves.
AB  - Besides the phase and group velocities, the amplitude of guided wave mode is also
      frequency dependent. This amplitude dispersion also influences the performance of
      guided wave methods in nondestructive evaluation (NDE) and structural health
      monitoring (SHM). In this paper, the effects of amplitude dispersion to the
      spectrum and waveform of a propagating wave-packet are investigated. It is shown
      that the amplitude dispersion results in distortion in the spectrum of guided
      wave response, and thus influences the waveform of the wave-packet. To remove
      these effects, an amplitude dispersion compensation method is established on the
      basis of Vold-Kalman filter and Taylor series expansion. The performance of that
      method is then investigated by experimental examples. The results show that with
      the application of the amplitude dispersion compensation, the time reversibility
      could be preserved, which ensures the applicability of the time reversal method
      for damage detection. Besides, through amplitude dispersion compensation, the
      testing resolution of guided waves could be improved, so that the structural
      features located in the close proximity may be separately identified.

PMID- 27706068
TI  - Community Theories of Change: Linking Environmental Justice to Sustainability
      through Stakeholder Perceptions in Milwaukee, (WI, USA).
AB  - Environmental justice and sustainability are compatible lenses, yet action toward
      equity is often missing from urban sustainability initiatives. This study aims to
      assess the cohesion of these frameworks in practice. To do this, we parse
      individuals' theories of change, or how they identify and propose to resolve
      environmental injustices in the pursuit of sustainability. We posit that these
      theories of change are comprised of three main components: (1) perceived
      environmental benefits and burdens; (2) the causal pathways of environmental and
      social injustice; and (3) visions for positive change. Drawing from 35
      stakeholder interviews in Milwaukee (WI, USA) we examine individual and
      institutional perspectives on environmental and social change and their links to
      the production of injustice. Our findings reveal that participants do not
      distinguish between environmental and social injustices. Instead, both social and
      environmental factors are implicated in injustice. Furthermore, we identify two
      mental maps for how social and economic change reproduce injustice. These
      findings suggest the need to reorient how urban injustice is considered and make
      efforts to acknowledge how a diversity of operational theories of change could
      either be divisive or could bring environmental justice and sustainability
      initiatives together.

PMID- 27706069
TI  - Spatial Distribution Balance Analysis of Hospitals in Wuhan.
AB  - The spatial distribution pattern of hospitals in Wuhan indicates a core in the
      central urban areas and a sparse distribution in the suburbs, particularly at the
      center of suburbs. This study aims to improve the gravity and Huff models to
      analyze healthcare accessibility and resources. Results indicate that healthcare
      accessibility in central urban areas is better than in the suburbs, where it
      increasingly worsens for the suburbs. A shortage of healthcare resources is
      observed in large-scale and high-class hospitals in central urban areas, whereas
      the resources of some hospitals in the suburbs are redundant. This study proposes
      the multi-criteria evaluation (MCE) analysis model for the location assessment in
      constructing new hospitals, which can effectively ameliorate healthcare
      accessibility in suburban areas. This study presents implications for the
      planning of urban healthcare facilities.

PMID- 27706066
TI  - Effects of Short-Term Exposure to Particulate Air Pollutants on the Inflammatory
      Response and Respiratory Symptoms: A Panel Study in Schoolchildren from Rural
      Areas of Japan.
AB  - The relationship between particulate air pollutants and respiratory symptoms in
      children has not been consistent among studies, potentially owing to differences
      in the inflammatory response to different particulate air pollutants. This study
      aimed to investigate the effect of particulate air pollutants on respiratory
      symptoms and the inflammatory response in schoolchildren. Three hundred-and-sixty
      children were included in the study. The children recorded daily respiratory
      symptom scores for October 2015. In addition, the daily amount of interleukin
      (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha production was assessed in
      THP1 cells stimulated with suspended particulate matter (SPM), which was
      collected every day during the study period. Generalized estimating equation
      logistic regression analyses were used to estimate the associations among
      respiratory symptoms and the daily levels of SPM, IL-6, IL-8, and TNF-alpha.
      Daily SPM levels were not associated with respiratory symptoms or the daily IL-6,
      IL-8, and TNF-alpha levels. Conversely, there was a significant association
      between respiratory symptoms and the daily IL-6, IL-8, and TNF-alpha levels.
      These results suggested that the effects of particulate air pollutants on
      respiratory symptoms in schoolchildren might depend more on the pro-inflammatory
      response to them than on their mass concentration.

PMID- 27706070
TI  - RT-qPCR Analysis of 15 Genes Encoding Putative Surface Proteins Involved in
      Adherence of Listeria monocytogenes.
AB  - L. monocytogenes adherence to food-associated abiotic surfaces and the
      development of biofilms as one of the underlying reasons for the contamination of
      ready-to-eat products is well known. The over-expression of internalins that
      improves adherence has been noted in cells growing as attached cells or at
      elevated incubation temperatures. However, the role of other internalin
      independent surface proteins as adhesins has been uncharacterized to date. Using
      two strains each of weakly- and strongly-adherent L. monocytogenes as platforms
      for temperature-dependent adherence assays and targeted mRNA analyses, these
      observations (i.e., sessile- and/or temperature-dependent gene expression) were
      further investigated. Microplate fluorescence assays of both surface-adherent
      strains exhibited significant (P < 0.05) adherence at higher incubation
      temperature (42  degrees C). Of the 15 genes selected for RT-qPCR, at least ten
      gene transcripts recovered from cells (weakly-adherent strain CW35, strongly
      adherent strain 99-38) subject to various growth conditions were over expressed
      [planktonic/30  degrees C (10), sessile/30  degrees C (12), planktonic/42 
      degrees C (10)] compared to their internal control (16SrRNA transcripts). Of four
      genes overexpressed in all three conditions tested, three and one were implicated
      as virulence factors and unknown function, respectively. PCR analysis of six
      unexpressed genes revealed that CW35 possessed an altered genome. The results
      suggest the presence of other internalin-independent adhesins (induced by growth
      temperature and/or substratum) and that a group of suspect protein members are
      worthy of further analysis for their potential role as surface adhesins. Analysis
      of the molecular basis of adherence properties of isolates of L. monocytogenes
      from food-associated facilities may help identify sanitation regimens to prevent
      cell attachment and biofilm formation on abiotic surfaces that could play a role
      in reducing foodborne illness resulting from Listeria biofilms.

PMID- 27706071
TI  - QUEST: Eliminating Online Supervised Learning for Efficient Classification
      Algorithms.
AB  - In this work, we introduce QUEST (QUantile Estimation after Supervised Training),
      an adaptive classification algorithm for Wireless Sensor Networks (WSNs) that
      eliminates the necessity for online supervised learning. Online processing is
      important for many sensor network applications. Transmitting raw sensor data puts
      high demands on the battery, reducing network life time. By merely transmitting
      partial results or classifications based on the sampled data, the amount of
      traffic on the network can be significantly reduced. Such classifications can be
      made by learning based algorithms using sampled data. An important issue,
      however, is the training phase of these learning based algorithms. Training a
      deployed sensor network requires a lot of communication and an impractical amount
      of human involvement. QUEST is a hybrid algorithm that combines supervised
      learning in a controlled environment with unsupervised learning on the location
      of deployment. Using the SITEX02 dataset, we demonstrate that the presented
      solution works with a performance penalty of less than 10% in 90% of the tests.
      Under some circumstances, it even outperforms a network of classifiers completely
      trained with supervised learning. As a result, the need for on-site supervised
      learning and communication for training is completely eliminated by our solution.

PMID- 27706072
TI  - Local Geographic Variation of Public Services Inequality: Does the Neighborhood
      Scale Matter?
AB  - This study aims to explore the effect of the neighborhood scale when estimating
      public services inequality based on the aggregation of social, environmental, and
      health-related indicators. Inequality analyses were carried out at three
      neighborhood scales: the original census blocks and two aggregated neighborhood
      units generated by the spatial "k"luster analysis by the tree edge removal
      (SKATER) algorithm and the self-organizing map (SOM) algorithm. Then, we combined
      a set of health-related public services indicators with the geographically
      weighted principal components analyses (GWPCA) and the principal components
      analyses (PCA) to measure the public services inequality across all multi-scale
      neighborhood units. Finally, a statistical test was applied to evaluate the scale
      effects in inequality measurements by combining all available field survey data.
      We chose Quito as the case study area. All of the aggregated neighborhood units
      performed better than the original census blocks in terms of the social
      indicators extracted from a field survey. The SKATER and SOM algorithms can help
      to define the neighborhoods in inequality analyses. Moreover, GWPCA performs
      better than PCA in multivariate spatial inequality estimation. Understanding the
      scale effects is essential to sustain a social neighborhood organization, which,
      in turn, positively affects social determinants of public health and public
      quality of life.

PMID- 27706073
TI  - Prevalence of Metabolic Syndrome among Korean Adolescents According to the
      National Cholesterol Education Program, Adult Treatment Panel III and
      International Diabetes Federation.
AB  - In both adults and children, metabolic syndrome (MetS) has been attributed to
      risk factors for type 2 diabetes and cardiovascular disease such as insulin
      resistance, abdominal obesity, hypertension, and dyslipidemia. This descriptive
      study aimed to compare the prevalence of MetS and diagnostic components according
      to the National Cholesterol Education Program, Adult Treatment Panel III (NCEP
      ATP III) and International Diabetes Federation (IDF) in 2330 Korean adolescents
      (10-18 years), using data from the 2010-2012 Korea National Health and Nutrition
      Examination Survey-V. The NCEP-ATP III and IDF were used to diagnose MetS and
      yielded prevalence rates of 5.7% and 2.1%, respectively, with no sex-related
      differences. The most frequent MetS diagnostic components according to the NCEP
      ATP III and IDF criteria were high triglyceride levels (21.2%) and low high
      density lipoprotein cholesterol levels (13.6%), respectively; approximately 50.1%
      and 33.1% of adolescents had at least one MetS diagnostic component according to
      the respective criteria. Both overweight/obese male and female adolescents
      exhibited significantly increased prevalence rates of MetS and related diagnostic
      components, compared to normal-weight adolescents. In conclusion, the prevalence
      rates of MetS and diagnostic components differ according to the NCEP-ATP III and
      IDF criteria. Henceforth, efforts are needed to establish diagnostic criteria for
      Korean adolescents.

PMID- 27706075
TI  - Urinary Sodium and Potassium Excretion and Carotid Atherosclerosis in Chinese Men
      and Women.
AB  - Limited studies have examined the association between sodium (Na) and potassium
      (K) levels and the risk of atherosclerosis. This study examined whether higher Na
      and Na/K levels and low K levels were independent risk factors for
      atherosclerosis. This community-based cross-sectional study included 3290
      subjects (1067 men and 2223 women) 40 to 75 years of age in Guangzhou, China,
      between 2011 and 2013. Urinary excretion of Na and K were measured from the first
      morning void, and creatinine-adjusted values were used. The intima-media
      thickness (IMT) of the carotid common artery and the carotid bifurcation was
      measured with high-resolution B-mode ultrasonography. Dietary K and Na intake and
      other covariates were obtained by face-to-face interviews. A significant positive
      association was seen between urinary Na excretion and carotid atherosclerosis
      after adjustment for age, sex, and other lifestyle covariates. The odds ratios
      (OR) and 95% confidence interval (CI) of the highest (vs. lowest) quartile of
      urinary Na were 1.32 (1.04-1.66) for carotid plaques, 1.48 (1.18-1.87) for
      increased common carotid artery IMT, and 1.55 (1.23-1.96) for increased carotid
      bifurcation IMT (all p-trend < 0.01). A similar positive association was observed
      between urinary Na/K levels and carotid plaque and increased IMT, and between
      dietary Na intake and increased bifurcation IMT. Regarding potassium data, we
      only found a significantly lower presence of carotid plaque (OR 0.72, 95% CI 0.57
      0.91) for quartile 2 (vs. 1) of urinary K. Our findings suggest that higher
      levels of urinary excretion Na and Na/K are significantly associated with greater
      presence of carotid atherosclerosis in Chinese adults.

PMID- 27706074
TI  - Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in
      Multiple Myeloma (MM).
AB  - Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an
      accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone
      destruction and BM failure. Despite recent advances in pharmacological therapy,
      MM remains a largely incurable pathology. Therefore, novel effective and less
      toxic agents are urgently necessary. In the last few years, pomegranate has been
      studied for its potential therapeutic properties including treatment and
      prevention of cancer. Pomegranate juice (PGJ) contains a number of potential
      active compounds including organic acids, vitamins, sugars, and phenolic
      components that are all responsible of the pro-apoptotic effects observed in
      tumor cell line. The aim of present investigation is to assess the
      antiproliferative and antiangiogenic potential of the PGJ in human multiple
      myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ
      in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic
      effects. Interestingly, sequential combination of bortezomib/PGJ improved the
      cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ
      on angiogenesis and cell migration/invasion. Interestingly, we observed an
      inhibitory effect on the tube formation, microvessel outgrowth aorting ring and
      decreased cell migration and invasion as showed by wound-healing and transwell
      assays, respectively. Analysis of angiogenic genes expression in endothelial
      cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ
      administration could represent a good tool in order to identify novel therapeutic
      strategies for MM treatment, exploiting its anti-proliferative and anti
      angiogenic effects. Finally, the present research supports the evidence that PGJ
      could play a key role of a future therapeutic approach for treatment of MM in
      order to optimize the pharmacological effect of bortezomib, especially as
      adjuvant after treatment.

PMID- 27706076
TI  - Modeling and Control of the Redundant Parallel Adjustment Mechanism on a
      Deployable Antenna Panel.
AB  - With the aim of developing multiple input and multiple output (MIMO) coupling
      systems with a redundant parallel adjustment mechanism on the deployable antenna
      panel, a structural control integrated design methodology is proposed in this
      paper. Firstly, the modal information from the finite element model of the
      structure of the antenna panel is extracted, and then the mathematical model is
      established with the Hamilton principle; Secondly, the discrete Linear Quadratic
      Regulator (LQR) controller is added to the model in order to control the
      actuators and adjust the shape of the panel. Finally, the engineering
      practicality of the modeling and control method based on finite element analysis
      simulation is verified.

PMID- 27706077
TI  - Assessing Walking Strategies Using Insole Pressure Sensors for Stroke Survivors.
AB  - Insole pressure sensors capture the different forces exercised over the different
      parts of the sole when performing tasks standing up such as walking. Using data
      analysis and machine learning techniques, common patterns and strategies from
      different users to achieve different tasks can be automatically extracted. In
      this paper, we present the results obtained for the automatic detection of
      different strategies used by stroke survivors when walking as integrated into an
      Information Communication Technology (ICT) enhanced Personalised Self-Management
      Rehabilitation System (PSMrS) for stroke rehabilitation. Fourteen stroke
      survivors and 10 healthy controls have participated in the experiment by walking
      six times a distance from chair to chair of approximately 10 m long. The
      Rivermead Mobility Index was used to assess the functional ability of each
      individual in the stroke survivor group. Several walking strategies are studied
      based on data gathered from insole pressure sensors and patterns found in stroke
      survivor patients are compared with average patterns found in healthy control
      users. A mechanism to automatically estimate a mobility index based on the
      similarity of the pressure patterns to a stereotyped stride is also used. Both
      data gathered from stroke survivors and healthy controls are used to evaluate the
      proposed mechanisms. The output of trained algorithms is applied to the PSMrS
      system to provide feedback on gait quality enabling stroke survivors to self
      manage their rehabilitation.

PMID- 27706079
TI  - A Power-Optimized Cooperative MAC Protocol for Lifetime Extension in Wireless
      Sensor Networks.
AB  - In wireless sensor networks, in order to satisfy the requirement of long working
      time of energy-limited nodes, we need to design an energy-efficient and lifetime
      extended medium access control (MAC) protocol. In this paper, a node cooperation
      mechanism that one or multiple nodes with higher channel gain and sufficient
      residual energy help a sender relay its data packets to its recipient is employed
      to achieve this objective. We first propose a transmission power optimization
      algorithm to prolong network lifetime by optimizing the transmission powers of
      the sender and its cooperative nodes to maximize their minimum residual energy
      after their data packet transmissions. Based on it, we propose a corresponding
      power-optimized cooperative MAC protocol. A cooperative node contention mechanism
      is designed to ensure that the sender can effectively select a group of
      cooperative nodes with the lowest energy consumption and the best channel quality
      for cooperative transmissions, thus further improving the energy efficiency.
      Simulation results show that compared to typical MAC protocol with direct
      transmissions and energy-efficient cooperative MAC protocol, the proposed
      cooperative MAC protocol can efficiently improve the energy efficiency and extend
      the network lifetime.

PMID- 27706078
TI  - Strategies for Extending Metabolomics Studies with Stable Isotope Labelling and
      Fluxomics.
AB  - This is a perspective from the peer session on stable isotope labelling and
      fluxomics at the Australian & New Zealand Metabolomics Conference (ANZMET) held
      from 30 March to 1 April 2016 at La Trobe University, Melbourne, Australia. This
      report summarizes the key points raised in the peer session which focused on the
      advantages of using stable isotopes in modern metabolomics and the challenges in
      conducting flux analyses. The session highlighted the utility of stable isotope
      labelling in generating reference standards for metabolite identification,
      absolute quantification, and in the measurement of the dynamic activity of
      metabolic pathways. The advantages and disadvantages of different approaches of
      fluxomics analyses including flux balance analysis, metabolic flux analysis and
      kinetic flux profiling were also discussed along with the use of stable isotope
      labelling in in vivo dynamic metabolomics. A number of crucial technical
      considerations for designing experiments and analyzing data with stable isotope
      labelling were discussed which included replication, instrumentation, methods of
      labelling, tracer dilution and data analysis. This report reflects the current
      viewpoint on the use of stable isotope labelling in metabolomics experiments,
      identifying it as a great tool with the potential to improve biological
      interpretation of metabolomics data in a number of ways.

PMID- 27706080
TI  - Identification, Molecular Cloning of IL-1beta and Its Expression Profile during
      Nocardia seriolae Infection in Largemouth Bass, Micropterus salmoides.
AB  - In the present study, IL-1beta cDNA was identified and analyzed from largemouth
      bass (Micropterus salmoides). Full length IL-1beta mRNA was obtained using Rapid
      Amplification of cDNA Ends (RACE), which contains 78 bp 3'-UTR, a 455 bp 5'-UTR,
      and an open reading frame (ORF) of 702 bp coding for 233 amino acid residues. The
      molecular weight and theoretical isoelectric point of largemouth bass IL-1beta
      protein was predicted to be 26.7 kDa and 6.08 respectively. A largemouth bass IL
      1beta phylogenetic analysis showed a close relation to the IL-1betas of striped
      trumpeter (Latris lineata), Chinese perch (Siniperca chuatsi), and Japanese sea
      bass (Lateolabrax japonicus). Peptidoglycan upregulated IL-1beta in the spleen
      and head kidney, while lipopolysaccharide upregulated detectable levels of IL
      1beta in the spleen only. Largemouth bass, challenged with Nocardia seriolae (1.0
      * 106 cfu/mL), showed a significant increase in IL-1beta at 3 and 5 days post
      infection (dpi) in the spleen, while in the head kidney significant expression
      was found at 2 and 3 dpi, peaking at 3 dpi. Furthermore, tumor necrosis factor
      alpha (TNF-alpha) showed significantly higher expression in the spleen at 3 and 5
      dpi, and in the head kidney at 1 and 3 dpi, with expression decreasing at 5 dpi
      in both tissues.

PMID- 27706081
TI  - Golgi-Related Proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in Cutaneous
      Melanoma: Patterns of Expression and Prognostic Significance.
AB  - GOLPH2 and GOLPH3 are Golgi-related proteins associated with aggressiveness and
      progression of a number of cancers. Their prognostic significance in melanoma has
      not yet been analyzed. We performed immunohistochemical analysis for GOLPH2 and
      GOLPH3 in 20 normal skin, 30 benign nevi and 100 primary melanoma tissue samples
      and evaluated their expression in three compartments: cancer cells, tumor
      associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). High
      levels of both proteins in melanoma cells were associated with characteristics of
      aggressive disease, and shorter disease-free survival (DFS) and cancer-specific
      overall survival (CSOS). On the contrary, increased numbers of GOLPH2-positive
      and GOLPH3-positive TAMs were observed in thinner, non-ulcerated tumors, with
      brisk lymphocytic reaction and absent lymphangioinvasion. Distant metastases were
      not observed among patients with high numbers of GOLPH2-positive TAMs. Increased
      expression of either protein in TAMs was related to prolonged CSOS and DFS.
      Similarly, GOLPH3-expressing CAFs were more frequent in thin melanomas with low
      mitotic rate, without ulceration and lymphangioinvasion. Moreover, increased
      GOLPH3-positive CAFs correlated with the absence of regional or distant
      metastases, and with longer CSOS and DFS. GOLPH2 expression was not observed in
      CAFs. Our results suggest that GOLPH2 and GOLPH3 play a role in melanoma
      progression and are potential targets for molecular-based therapies.

PMID- 27706082
TI  - Extraction of Natural Antioxidants from the Thelephora ganbajun Mushroom by an
      Ultrasound-Assisted Extraction Technique and Evaluation of Antiproliferative
      Activity of the Extract against Human Cancer Cells.
AB  - The Thelephora ganbajun mushroom has been found to be a potential rich source of
      natural antioxidants. In this study, an ultrasound-assisted extraction (UAE)
      technique together with GRAS (generally recognized as safe) solvents (ethanol and
      water) was used to maximize the extraction of antioxidants from Thelephora
      ganbajun. Five extraction parameters (ethanol concentration, solvent to solid
      ratio, extraction time, temperature and ultrasound power) were investigated by
      single-factor experiments, and then a central composite rotatable design was
      employed to study interaction of three key extraction parameters. The optimum
      conditions were as follows: 57.38% ethanol, 70.15 mL/g solvent to solid ratio,
      10.58 min extraction time, 40  degrees C extraction temperature and 500 W
      ultrasound power. Under the optimum conditions, the antioxidant activity obtained
      was 346.98 +/- 12.19 umol Trolox/g DW, in accordance with the predicted value of
      344.67 umol Trolox/g DW. Comparison of UAE with conventional maceration and
      Soxhlet extraction, the UAE method showed stronger extract efficiency in a
      shorter extraction time. These results showed that UAE was an effective technique
      to extract antioxidants from Thelephora ganbajun. Furthermore, the extracts
      obtained under the optimized conditions exhibited antiproliferative activities
      toward human lung (A549), breast (MCF-7), liver (HepG2) and colon (HT-29) cancer
      cells, especially for liver and lung cancer cells. In addition, rutin, 2
      hydrocinnamic acid and epicatechin were identified in the extract, which might
      contribute to antioxidant and antiproliferative activities.

PMID- 27706083
TI  - Fermentation Results and Chemical Composition of Agricultural Distillates
      Obtained from Rye and Barley Grains and the Corresponding Malts as a Source of
      Amylolytic Enzymes and Starch.
AB  - The objective of this study was to determine the efficiency of rye and barley
      starch hydrolysis in mashing processes using cereal malts as a source of
      amylolytic enzymes and starch, and to establish the volatile profile of the
      obtained agricultural distillates. In addition, the effects of the pretreatment
      method of unmalted cereal grains on the physicochemical composition of the
      prepared mashes, fermentation results, and the composition of the obtained
      distillates were investigated. The raw materials used were unmalted rye and
      barley grains, as well as the corresponding malts. All experiments were first
      performed on a semi-technical scale, and then verified under industrial
      conditions in a Polish distillery. The fermentable sugars present in sweet mashes
      mostly consisted of maltose, followed by glucose and maltotriose. Pressure
      thermal treatment of unmalted cereals, and especially rye grains, resulted in
      higher ethanol content in mashes in comparison with samples subjected to
      pressureless liberation of starch. All agricultural distillates originating from
      mashes containing rye and barley grains and the corresponding malts were
      characterized by low concentrations of undesirable compounds, such as
      acetaldehyde and methanol. The distillates obtained under industrial conditions
      contained lower concentrations of higher alcohols (apart from 1-propanol) than
      those obtained on a semi-technical scale.

PMID- 27706084
TI  - Anti-Inflammatory Activity of Natural Products.
AB  - This article presents highlights of the published literature regarding the anti
      inflammatory activities of natural products. Many review articles were published
      in this regard, however, most of them have presented this important issue from a
      regional, limited perspective. This paper summarizes the vast range of review and
      research articles that have reported on the anti-inflammatory effects of extracts
      and/or pure compounds derived from natural products. Moreover, this review
      pinpoints some interesting traditionally used medicinal plants that were not
      investigated yet.

PMID- 27706085
TI  - Design and Construction of a Bilateral Haptic System for the Remote Assessment of
      the Stiffness and Range of Motion of the Hand.
AB  - The use of haptic devices in the rehabilitation of impaired limbs has become
      rather popular, given the proven effectiveness in promoting recovery. In a
      standard framework, such devices are used in rehabilitation centers, where
      patients interact with virtual tasks, presented on a screen. To track their
      sessions, kinematic/dynamic parameters or performance scores are recorded.
      However, as Internet access is now available at almost every home and in order to
      reduce the hospitalization time of the patient, the idea of doing rehabilitation
      at home is gaining wide consent. Medical care programs can be synchronized with
      the home rehabilitation device; patient data can be sent to the central server
      that could redirect to the therapist laptop (tele-healthcare). The controversial
      issue is that the recorded data do not actually represent the clinical conditions
      of the patients according to the medical assessment scales, forcing them to
      frequently undergo clinical tests at the hospital. To respond to this demand, we
      propose the use of a bilateral master/slave haptic system that could allow the
      clinician, who interacts with the master, to assess remotely and in real time the
      clinical conditions of the patient that uses the home rehabilitation device as
      the slave. In this paper, we describe a proof of concept to highlight the main
      issues of such an application, limited to one degree of freedom, and to the
      measure of the stiffness and range of motion of the hand.

PMID- 27706086
TI  - Towards Real-Time Detection of Gait Events on Different Terrains Using Time
      Frequency Analysis and Peak Heuristics Algorithm.
AB  - Real-time detection of gait events can be applied as a reliable input to control
      drop foot correction devices and lower-limb prostheses. Among the different
      sensors used to acquire the signals associated with walking for gait event
      detection, the accelerometer is considered as a preferable sensor due to its
      convenience of use, small size, low cost, reliability, and low power consumption.
      Based on the acceleration signals, different algorithms have been proposed to
      detect toe off (TO) and heel strike (HS) gait events in previous studies. While
      these algorithms could achieve a relatively reasonable performance in gait event
      detection, they suffer from limitations such as poor real-time performance and
      are less reliable in the cases of up stair and down stair terrains. In this
      study, a new algorithm is proposed to detect the gait events on three walking
      terrains in real-time based on the analysis of acceleration jerk signals with a
      time-frequency method to obtain gait parameters, and then the determination of
      the peaks of jerk signals using peak heuristics. The performance of the newly
      proposed algorithm was evaluated with eight healthy subjects when they were
      walking on level ground, up stairs, and down stairs. Our experimental results
      showed that the mean F1 scores of the proposed algorithm were above 0.98 for HS
      event detection and 0.95 for TO event detection on the three terrains. This
      indicates that the current algorithm would be robust and accurate for gait event
      detection on different terrains. Findings from the current study suggest that the
      proposed method may be a preferable option in some applications such as drop foot
      correction devices and leg prostheses.

PMID- 27706088
TI  - Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic
      Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?
AB  - In the congestive heart failure (CHF) setting, chronic hyponatremia is very
      common. The present review aims at addressing topics relevant to the
      pathophysiology of hyponatremia in the course of CHF as well as its optimal
      treatment, including the main advantages and the limitations resulting from the
      use of the available dietary and pharmacological measures approved for the
      treatment of this electrolytic trouble. A narrative review is carried out in
      order to represent the main modalities of therapy for chronic hyponatremia that
      frequently complicates CHF. The limits of usual therapies implemented for CHF
      related chronic hyponatremia are outlined, while an original analysis of the main
      advancements achieved with the use of vasopressin receptor antagonists (VRAs) is
      also executed. The European regulatory restrictions that currently limit the use
      of VRAs in the management of CHF are substantially caused by financial concerns,
      i.e., the high costs of VRA therapy. A thoughtful reworking of current
      restrictions would be warranted in order to enable VRAs to be usefully associated
      to loop diuretics for decongestive treatment of CHF patients with hyponatremia.

PMID- 27706087
TI  - Characterization of Airborne Particles Collected from Car Engine Air Filters
      Using SEM and EDX Techniques.
AB  - Particulate matter accumulated on car engine air-filters (CAFs) was examined in
      order to investigate the potential use of these devices as efficient samplers for
      collecting street level air that people are exposed to. The morphology,
      microstructure, and chemical composition of a variety of particles were studied
      using scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX). The
      particulate matter accumulated by the CAFs was studied in two categories; the
      first was of removed particles by friction, and the second consisted of particles
      retained on the filters. Larger particles with a diameter of 74-10 um were
      observed in the first category. In the second one, the detected particles had a
      diameter between 16 and 0.7 um. These particles exhibited different morphologies
      and composition, indicating mostly a soil origin. The elemental composition
      revealed the presence of three groups: mineral (clay and asphalt), metallic
      (mainly Fe), and biological particles (vegetal and animal debris). The
      palynological analysis showed the presence of pollen grains associated with urban
      plants. These results suggest that CAFs capture a mixture of atmospheric
      particles, which can be analyzed in order to monitor urban air. Thus, the
      continuous availability of large numbers of filters and the retroactivity
      associated to the car routes suggest that these CAFs are very useful for studying
      the high traffic zones within a city.

PMID- 27706089
TI  - Susceptibility to Heat-Related Fluid and Electrolyte Imbalance Emergency
      Department Visits in Atlanta, Georgia, USA.
AB  - Identification of populations susceptible to heat effects is critical for
      targeted prevention and more accurate risk assessment. Fluid and electrolyte
      imbalance (FEI) may provide an objective indicator of heat morbidity. Data on
      daily ambient temperature and FEI emergency department (ED) visits were collected
      in Atlanta, Georgia, USA during 1993-2012. Associations of warm-season same-day
      temperatures and FEI ED visits were estimated using Poisson generalized linear
      models. Analyses explored associations between FEI ED visits and various
      temperature metrics (maximum, minimum, average, and diurnal change in ambient
      temperature, apparent temperature, and heat index) modeled using linear,
      quadratic, and cubic terms to allow for non-linear associations. Effect
      modification by potential determinants of heat susceptibility (sex; race;
      comorbid congestive heart failure, kidney disease, and diabetes; and neighborhood
      poverty and education levels) was assessed via stratification. Higher warm-season
      ambient temperature was significantly associated with FEI ED visits, regardless
      of temperature metric used. Stratified analyses suggested heat-related risks for
      all populations, but particularly for males. This work highlights the utility of
      FEI as an indicator of heat morbidity, the health threat posed by warm-season
      temperatures, and the importance of considering susceptible populations in heat
      health research.

PMID- 27706090
TI  - Interactions of beta-Conglycinin (7S) with Different Phenolic Acids-Impact on
      Structural Characteristics and Proteolytic Degradation of Proteins.
AB  - p-Coumalic acid (PCA), caffeic acid (CA), gallic acid (GA) and chlorogenic acid
      (CGA) are the major phenolic acids that co-exist with soy protein components in
      foodstuffs. Surprisingly, there are only a handful of reports that describe their
      interaction with beta-Conglycinin (7S), a major soy protein. In this report, we
      investigated the interaction between phenolic acids and soy protein 7S and
      observed an interaction between each of these phenolic acids and soy protein 7S,
      which was carried out by binding. Further analysis revealed that the binding
      activity of the phenolic acids was structure dependent. Here, the binding
      affinity of CA and GA towards 7S was found to be stronger than that of PCA,
      because CA and GA have one more hydroxyl group. Interestingly, the binding of
      phenolic acids with soy protein 7S did not affect protein digestion by pepsin and
      trypsin. These findings aid our understanding of the relationship between
      different phenolic acids and proteins in complex food systems.

PMID- 27706092
TI  - Black-White Disparities in Criminal Justice Referrals to Drug Treatment:
      Addressing Treatment Need or Expanding the Diagnostic Net?
AB  - Slightly more than half of admissions to U.S. publicly-funded treatment for
      marijuana use are referred by the criminal justice system; this pattern has
      remained for at least 20 years. Nationally, Blacks comprise nearly a third of
      treatment admissions for marijuana use. This article explores the interplay
      between race and criminal justice referrals to treatment for marijuana use. Using
      data from the (U.S.) 2011 Treatment Episode Data Set, we examine the relationship
      between race and diagnosis of cannabis use disorder (dependence versus abuse)
      among referrals to community-based treatment in North Carolina. We compare
      Black/White differences in cannabis diagnoses across four referral sources: the
      criminal justice system, healthcare providers, self, and other sources. Race was
      significantly related to type of diagnosis across all four referral sources,
      however, the nature of the relationship was distinctly different among criminal
      justice referrals with Whites being more likely than Blacks to be diagnosed with
      cannabis dependence. Moreover, the marijuana use profiles of criminal justice
      referrals differed substantially from individuals referred by other sources. The
      findings suggest that diagnoses of cannabis abuse (rather than dependence) may
      have worked to widen the diagnostic net by "capturing" individuals under control
      of the criminal justice system who manifested few problems with marijuana use,
      other than their involvement in the criminal justice system. The potential for a
      net-widening effect appeared to be most pronounced for Blacks.

PMID- 27706091
TI  - Modulation of Compartmentalised Cyclic Nucleotide Signalling via Local Inhibition
      of Phosphodiesterase Activity.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) are the only enzymes that degrade the
      cyclic nucleotides cAMP and cGMP, and play a key role in modulating the amplitude
      and duration of the signal delivered by these two key intracellular second
      messengers. Defects in cyclic nucleotide signalling are known to be involved in
      several pathologies. As a consequence, PDEs have long been recognized as
      potential drug targets, and they have been the focus of intense research for the
      development of therapeutic agents. A number of PDE inhibitors are currently
      available for the treatment of disease, including obstructive pulmonary disease,
      erectile dysfunction, and heart failure. However, the performance of these drugs
      is not always satisfactory, due to a lack of PDE-isoform specificity and their
      consequent adverse side effects. Recent advances in our understanding of
      compartmentalised cyclic nucleotide signalling and the role of PDEs in local
      regulation of cAMP and cGMP signals offers the opportunity for the development of
      novel strategies for therapeutic intervention that may overcome the current
      limitation of conventional PDE inhibitors.

PMID- 27706093
TI  - Natural and Synthetic Coumarins with Effects on Inflammation.
AB  - In this review, we will present the different aspects of coumarins and
      derivatives, from natural origins or synthetically prepared, and their action on
      inflammation. Coumarins and also furo- and pyranocoumarins are found in many
      different plants. These compounds are very often investigated for antioxidant
      properties. Other biological properties are also possible and anti-inflammation
      activity is one of these. As coumarins are also available quite easily via
      synthesis, natural ones can be prepared this way but derivatives with special
      substituents are also feasible. A review on the same topic appeared in 2004 and
      our contribution will take into account everything published since then.

PMID- 27706094
TI  - 3D Printed Dry EEG Electrodes.
AB  - Electroencephalography (EEG) is a procedure that records brain activity in a non
      invasive manner. The cost and size of EEG devices has decreased in recent years,
      facilitating a growing interest in wearable EEG that can be used out-of-the-lab
      for a wide range of applications, from epilepsy diagnosis, to stroke
      rehabilitation, to Brain-Computer Interfaces (BCI). A major obstacle for these
      emerging applications is the wet electrodes, which are used as part of the EEG
      setup. These electrodes are attached to the human scalp using a conductive gel,
      which can be uncomfortable to the subject, causes skin irritation, and some gels
      have poor long-term stability. A solution to this problem is to use dry
      electrodes, which do not require conductive gel, but tend to have a higher noise
      floor. This paper presents a novel methodology for the design and manufacture of
      such dry electrodes. We manufacture the electrodes using low cost desktop 3D
      printers and off-the-shelf components for the first time. This allows quick and
      inexpensive electrode manufacturing and opens the possibility of creating
      electrodes that are customized for each individual user. Our 3D printed
      electrodes are compared against standard wet electrodes, and the performance of
      the proposed electrodes is suitable for BCI applications, despite the presence of
      additional noise.

PMID- 27706096
TI  - Transformation of Tertiary Benzyl Alcohols into the Vicinal Halo-Substituted
      Derivatives Using N-Halosuccinimides.
AB  - The efficiency of direct conversion of tertiary alcohols bearing a beta-hydrogen
      atom to vicinal halohydrins-chlorohydrins and bromohydrins-under green reaction
      conditions was tested preliminarily on model tertiary benzyl alcohols. Tertiary
      alcohols were successfully directly halogenated to vicinal halohydrins with N
      halosuccinimide in aqueous media. The efficiency of the reaction in water was
      significantly improved in the presence of sodium dodecyl sulphate as the
      surfactant.

PMID- 27706095
TI  - Soluble Fiber with High Water-Binding Capacity, Swelling Capacity, and
      Fermentability Reduces Food Intake by Promoting Satiety Rather Than Satiation in
      Rats.
AB  - To understand whether soluble fiber (SF) with high water-binding capacity (WBC),
      swelling capacity (SC) and fermentability reduces food intake and whether it does
      so by promoting satiety or satiation or both, we investigated the effects of
      different SFs with these properties on the food intake in rats. Thirty-two male
      Sprague-Dawley rats were randomized to four equal groups and fed the control diet
      or diet containing 2% konjac flour (KF), pregelatinized waxy maize starch (PWMS)
      plus guar gum (PG), and PWMS starch plus xanthan gum (PX) for three weeks, with
      the measured values of SF, WBC, and SC in the four diets following the order of
      PG > KF > PX > control. Food intake, body weight, meal pattern, behavioral
      satiety sequence, and short-chain fatty acids (SCFAs) in cecal content were
      evaluated. KF and PG groups reduced the food intake, mainly due to the decreased
      feeding behavior and increased satiety, as indicated by decreased meal numbers
      and increased inter-meal intervals. Additionally, KF and PG groups increased
      concentrations of acetate acid, propionate acid, and SCFAs in the cecal contents.
      Our results indicate that SF with high WBC, SC, and fermentability reduces food
      intake-probably by promoting a feeling of satiety in rats to decrease their
      feeding behavior.

PMID- 27706097
TI  - Anti-Inflammatory Effects of Aspalathus linearis and Cyclopia spp. Extracts in a
      UVB/Keratinocyte (HaCaT) Model Utilising Interleukin-1alpha Accumulation as
      Biomarker.
AB  - Ultraviolet B (UVB) radiation is one of the major predisposing risk factors of
      skin cancer. The anticancer and photoprotective effects of unoxidized rooibos
      (Aspalathus linearis) and honeybush (Cyclopia) herbal teas, containing high
      levels of dihydrochalones and xanthones, respectively, have been demonstrated in
      skin cancer models in vivo. In the current study, the anti-inflammatory effects
      of methanol and aqueous extracts of these herbal teas were investigated in a
      UVB/HaCaT keratinocyte model with intracellular interleukin-1alpha (icIL-1alpha)
      accumulation as a biomarker. Extracts of green tea (Camellia sinensis) served as
      benchmark. Both extracts of green tea and rooibos, as well as the aqueous extract
      of C. intermedia, enhanced UVB-induced inhibition of cell viability,
      proliferation and induction of apoptosis, facilitating the removal of icIL
      1alpha. The underlying mechanisms may involve mitochondrial dysfunction
      exhibiting pro-oxidant responses via polyphenol-iron interactions. The methanol
      extracts of honeybush, however, protected against UVB-induced reduction of cell
      growth parameters, presumably via antioxidant mechanisms that prevented the
      removal of highly inflamed icIL-1alpha-containing keratinocytes via apoptosis.
      The dual antioxidant and/or pro-oxidant role of the polyphenolic herbal tea
      constituents should be considered in developing preventive strategies against UVB
      induced skin carcinogenesis. The indirect removal of UVB damaged keratinocytes by
      herbal tea extracts via apoptosis may find application in the prevention of photo
      induced inflammation.

PMID- 27706098
TI  - Effect of Raw Material, Pressing and Glycosidase on the Volatile Compound
      Composition of Wine Made From Goji Berries.
AB  - This study investigated the effect of raw material, pressing, and glycosidase on
      the aromatic profile of goji berry wine. The free-run and the pressed juice of
      dried and fresh goji berries were used for wine production, whereas glycosidase
      was applied to wine after fermentation. Dried goji berry fermented wine exhibited
      much stronger fruity, floral, caramel, and herbaceous odors due to higher levels
      of esters, beta-ionone and methionol. However, fresh berry fermented wine
      possessed stronger chemical notes due to higher levels of 4-ethylphenol. Pressing
      treatment reduced the fruity and caramel odors in these fermented wines, and
      fresh berry free-run juice fermented wine exhibited the least floral aroma.
      Glycosidase addition did not alter the aromatic composition of wines. The
      principal component analysis indicated that goji raw material played a primary
      role in differentiating the aromatic profiles of the wines due to the difference
      on the content of 20 esters, nine benzenes, eight aldehydes/ketones, three acids,
      two alcohols and six other volatiles. The content differences on isopentyl
      alcohol, styrene, benzyl alcohol, 1-octanol, (E)-5-decen-1-ol, 1-hexanol, and
      beta-cyclocitral resulted in the segregation of the wines with and without the
      pressing treatment, especially for fresh berry fermented wine.

PMID- 27706099
TI  - Conditional Entropy and Location Error in Indoor Localization Using Probabilistic
      Wi-Fi Fingerprinting.
AB  - Localization systems are increasingly valuable, but their location estimates are
      only useful when the uncertainty of the estimate is known. This uncertainty is
      currently calculated as the location error given a ground truth, which is then
      used as a static measure in sometimes very different environments. In contrast,
      we propose the use of the conditional entropy of a posterior probability
      distribution as a complementary measure of uncertainty. This measure has the
      advantage of being dynamic, i.e., it can be calculated during localization based
      on individual sensor measurements, does not require a ground truth, and can be
      applied to discrete localization algorithms. Furthermore, for every consistent
      location estimation algorithm, both the location error and the conditional
      entropy measures must be related, i.e., a low entropy should always correspond
      with a small location error, while a high entropy can correspond with either a
      small or large location error. We validate this relationship experimentally by
      calculating both measures of uncertainty in three publicly available datasets
      using probabilistic Wi-Fi fingerprinting with eight different implementations of
      the sensor model. We show that the discrepancy between these measures, i.e., many
      location estimates having a high location error while simultaneously having a low
      conditional entropy, is largest for the least realistic implementations of the
      probabilistic sensor model. Based on the results presented in this paper, we
      conclude that conditional entropy, being dynamic, complementary to location
      error, and applicable to both continuous and discrete localization, provides an
      important extra means of characterizing a localization method.

PMID- 27706101
TI  - Methodological Comparison between a Novel Automatic Sampling System for Gas
      Chromatography versus Photoacoustic Spectroscopy for Measuring Greenhouse Gas
      Emissions under Field Conditions.
AB  - Trace gases such as nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2)
      are climate-related gases, and their emissions from agricultural livestock barns
      are not negligible. Conventional measurement systems in the field (Fourier
      transform infrared spectroscopy (FTIR); photoacoustic system (PAS)) are not
      sufficiently sensitive to N2O. Laser-based measurement systems are highly
      accurate, but they are very expensive to purchase and maintain. One cost
      effective alternative is gas chromatography (GC) with electron capture detection
      (ECD), but this is not suitable for field applications due to radiation.
      Measuring samples collected automatically under field conditions in the
      laboratory at a subsequent time presents many challenges. This study presents a
      sampling designed to promote laboratory analysis of N2O concentrations sampled
      under field conditions. Analyses were carried out using PAS in the field (online
      system) and GC in the laboratory (offline system). Both measurement systems
      showed a good correlation for CH4 and CO2 concentrations. Measured N2O
      concentrations were near the detection limit for PAS. GC achieved more reliable
      results for N2O in very low concentration ranges.

PMID- 27706100
TI  - Plant Resistance Inducers against Pathogens in Solanaceae Species-From Molecular
      Mechanisms to Field Application.
AB  - This review provides a current summary of plant resistance inducers (PRIs) that
      have been successfully used in the Solanaceae plant family to protect against
      pathogens by activating the plant's own defence. Solanaceous species include many
      important crops such as potato and tomato. We also present findings regarding the
      molecular processes after application of PRIs, even if the number of such studies
      still remains limited in this plant family. In general, there is a lack of
      patterns regarding the efficiency of induced resistance (IR) both between and
      within solanaceous species. In many cases, a hypersensitivity-like reaction needs
      to form in order for the PRI to be efficient. "-Omics" studies have already given
      insight in the complexity of responses, and can explain some of the differences
      seen in efficacy of PRIs between and within species as well as towards different
      pathogens. Finally, examples of field applications of PRIs for solanaceous crops
      are presented and discussed. We predict that PRIs will play a role in future
      plant protection strategies in Solanaceae crops if they are combined with other
      means of disease control in different spatial and temporal combinations.

PMID- 27706102
TI  - The Redox Status of Cancer Cells Supports Mechanisms behind the Warburg Effect.
AB  - To better understand the energetic status of proliferating cells, we have
      measured the intracellular pH (pHi) and concentrations of key metabolites, such
      as adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), and
      nicotinamide adenine dinucleotide phosphate (NADP) in normal and cancer cells,
      extracted from fresh human colon tissues. Cells were sorted by elutriation and
      segregated in different phases of the cell cycle (G0/G1/S/G2/M) in order to study
      their redox (NAD, NADP) and bioenergetic (ATP, pHi) status. Our results show that
      the average ATP concentration over the cell cycle is higher and the pHi is
      globally more acidic in normal proliferating cells. The NAD+/NADH and NADP+/NADPH
      redox ratios are, respectively, five times and ten times higher in cancer cells
      compared to the normal cell population. These energetic differences in normal and
      cancer cells may explain the well-described mechanisms behind the Warburg effect.
      Oscillations in ATP concentration, pHi, NAD+/NADH, and NADP+/NADPH ratios over
      one cell cycle are reported and the hypothesis addressed. We also investigated
      the mitochondrial membrane potential (MMP) of human and mice normal and cancer
      cell lines. A drastic decrease of the MMP is reported in cancer cell lines
      compared to their normal counterparts. Altogether, these results strongly support
      the high throughput aerobic glycolysis, or Warburg effect, observed in cancer
      cells.

PMID- 27706103
TI  - In Vitro Metabolic Studies of REV-ERB Agonists SR9009 and SR9011.
AB  - SR9009 and SR9011 are attractive as performance-enhancing substances due to their
      REV-ERB agonist effects and thus circadian rhythm modulation activity. Although
      no pharmaceutical preparations are available yet, illicit use of SR9009 and
      SR9011 for doping purposes can be anticipated, especially since SR9009 is
      marketed in illicit products. Therefore, the aim was to identify potential
      diagnostic metabolites via in vitro metabolic studies to ensure effective
      (doping) control. The presence of SR9009 could be demonstrated in a black market
      product purchased over the Internet. Via human liver microsomal metabolic assays,
      eight metabolites were detected for SR9009 and fourteen metabolites for SR9011 by
      liquid chromatography-high resolution mass spectrometry (LC-HRMS). Structure
      elucidation was performed for all metabolites by LC-HRMS product ion scans in
      both positive and negative ionization mode. Retrospective data analysis was
      applied to 1511 doping control samples previously analyzed by a full-scan LC-HRMS
      screening method to verify the presence of SR9009, SR9011 and their metabolites.
      So far, the presence of neither the parent compound nor the metabolites could be
      detected in routine urine samples. However, to further discourage use of these
      potentially harmful compounds, incorporation of SR9009 and SR9011 into screening
      methods is highly recommended.

PMID- 27706104
TI  - Quasi-3D Modeling and Efficient Simulation of Laminar Flows in Microfluidic
      Devices.
AB  - A quasi-3D model has been developed to simulate the flow in planar microfluidic
      systems with low Reynolds numbers. The model was developed by decomposing the
      flow profile along the height of a microfluidic system into a Fourier series. It
      was validated against the analytical solution for flow in a straight rectangular
      channel and the full 3D numerical COMSOL Navier-Stokes solver for flow in a T
      channel. Comparable accuracy to the full 3D numerical solution was achieved by
      using only three Fourier terms with a significant decrease in computation time.
      The quasi-3D model was used to model flows in a micro-flow cytometer chip on a
      desktop computer and good agreement between the simulation and the experimental
      results was found.

PMID- 27706105
TI  - Biological Control of Mosquito Vectors: Past, Present, and Future.
AB  - Mosquitoes represent the major arthropod vectors of human disease worldwide
      transmitting malaria, lymphatic filariasis, and arboviruses such as dengue virus
      and Zika virus. Unfortunately, no treatment (in the form of vaccines or drugs) is
      available for most of these diseases
      andvectorcontrolisstillthemainformofprevention.
      Thelimitationsoftraditionalinsecticide-based strategies, particularly the
      development of insecticide resistance, have resulted in significant efforts to
      develop alternative eco-friendly methods. Biocontrol strategies aim to be
      sustainable and target a range of different mosquito species to reduce the
      current reliance on insecticide-based mosquito control. In thisreview, weoutline
      non-insecticide basedstrategiesthat havebeenimplemented orare currently being
      tested. We also highlight the use of mosquito behavioural knowledge that can be
      exploited for control strategies.

PMID- 27706106
TI  - Genome-Wide Identification, Characterization and Expression Analysis of the
      Solute Carrier 6 Gene Family in Silkworm (Bombyx mori).
AB  - The solute carrier 6 (SLC6) gene family, initially known as the neurotransmitter
      transporters, plays vital roles in the regulation of neurotransmitter signaling,
      nutrient absorption and motor behavior. In this study, a total of 16 candidate
      genes were identified as SLC6 family gene homologs in the silkworm (Bombyx mori)
      genome. Spatio-temporal expression patterns of silkworm SLC6 gene transcripts
      indicated that these genes were highly and specifically expressed in midgut,
      brain and gonads; moreover, these genes were expressed primarily at the feeding
      stage or adult stage. Levels of expression for most midgut-specific and midgut
      enriched gene transcripts were down-regulated after starvation but up-regulated
      after re-feeding. In addition, we observed that expression levels of these genes
      except for BmSLC6-15 and BmGT1 were markedly up-regulated by a juvenile hormone
      analog. Moreover, brain-enriched genes showed differential expression patterns
      during wandering and mating processes, suggesting that these genes may be
      involved in modulating wandering and mating behaviors. Our results improve our
      understanding of the expression patterns and potential physiological functions of
      the SLC6 gene family, and provide valuable information for the comprehensive
      functional analysis of the SLC6 gene family.

PMID- 27706108
TI  - OprD Repression upon Metal Treatment Requires the RNA Chaperone Hfq in
      Pseudomonas aeruginosa.
AB  - The metal-specific CzcRS two-component system in Pseudomonas aeruginosa is
      involved in the repression of the OprD porin, causing in turn carbapenem
      antibiotic resistance in the presence of high zinc concentration. It has also
      been shown that CzcR is able to directly regulate the expression of multiple
      genes including virulence factors. CzcR is therefore an important regulator
      connecting (i) metal response, (ii) pathogenicity and (iii) antibiotic resistance
      in P. aeruginosa. Recent data have suggested that other regulators could
      negatively control oprD expression in the presence of zinc. Here we show that the
      RNA chaperone Hfq is a key factor acting independently of CzcR for the repression
      of oprD upon Zn treatment. Additionally, we found that an Hfq-dependent mechanism
      is necessary for the localization of CzcR to the oprD promoter, mediating oprD
      transcriptional repression. Furthermore, in the presence of Cu, CopR, the
      transcriptional regulator of the CopRS two-component system also requires Hfq for
      oprD repression. Altogether, these results suggest important roles for this RNA
      chaperone in the context of environment-sensing and antibiotic resistance in P.
      aeruginosa.

PMID- 27706107
TI  - The SaeRS Two-Component System of  Staphylococcus aureus.
AB  - In the Gram-positive pathogenic bacterium Staphylococcus aureus, the SaeRS
      twocomponent system (TCS) plays a major role in controlling the production of
      over 20 virulence factors including hemolysins, leukocidins, superantigens,
      surface proteins, and proteases. The SaeRS TCS is composed of the sensor
      histidine kinase SaeS, response regulator SaeR, and two auxiliary proteins SaeP
      and SaeQ. Since its discovery in 1994, the sae locus has been studied
      extensively, and its contributions to staphylococcal virulence and pathogenesis
      have been well documented and understood; however, the molecular mechanism by
      which the SaeRS TCS receives and processes cognate signals is not. In this
      article, therefore, we review the literature focusing on the signaling mechanism
      and its interaction with other global regulators.

PMID- 27706109
TI  - 2-(2-Phenylethyl)chromone Derivatives of Agarwood Originating from Gyrinops
      salicifolia.
AB  - Three new2-(2-phenylethyl)chromone derivatives (1-3) and a new2-(2
      phenylethenyl)chromone derivative (4), together with two known 2-(2
      phenylethyl)chromone derivatives (5-6), were isolated from agarwood originating
      from Gyrinops salicifolia Ridl. The structures of compounds 1-4 were elucidated
      by comprehensive spectroscopic techniques (UV, IR, 1D and 2D-NMR) and MS
      analysis, as well as by comparison with the literature. Compounds 1, 2, and 5
      showed moderate cytotoxicity against human tumor K562, BEL-7402, and SGC-7901
      cell lines with IC50 values of 5.76 to 20.1 uM.

PMID- 27706112
TI  - Oxygenized low density lipoprotein down-regulates the TRPV4 protein expression of
      macrophage through activation of peroxisome proliferator-activated receptor
      gamma.
AB  - BACKGROUND: TRPV4, a non-selective cation channel, is involved in lipometabolism
      and atherosclerosis. However, whether TRPV4 participates in oxygenized low
      density lipoprotein (oxLDL)-induced foam cell formation remains unknown. The
      present study investigates the effect of oxLDL on the expression of TRPV4 in
      macrophages and its underlying mechanisms. METHODS: The expression of TRPV4 in
      RAW264.7 and phorbol-12-myristate-13-acetate (PMA) induced U937, THP-1 cells was
      detected by immunofluorescence, and western blot was used to detect the TRPV4
      expression before and after PMA induction. Each cell line was divided into three
      groups, including control group, native low-density lipoprotein (nLDL) (100
      MUg/mL) group and oxLDL (100MUg/mL) group; the expression of TRPV4 in each group
      was measured using immunohistochemistry and western blot. TRPV4 protein
      expression was detected by western blot after RAW 264.7 cells were treated with
      0, 0.01 MUM, 0.1 MUM and 1 MUM T0070907 or preincubated with 0.1 MUM T0070709 for
      1 h before incubation with oxLDL for 24 h. RESULTS: In all macrophage cell lines,
      TRPV4 was widely expressed. PMA increased TRPV4 expression in U937 and THP-1
      cells. There was no significant difference in TRPV4 expression in the nLDL group
      compared to that in the control group; however a significant reduction in TRPV4
      expression was detected in the oxLDL group compared to that in the control and
      nLDL groups using measurements obtained from both immunohistochemistry and
      western blot. The PPARgamma inhibitor T0070907 enhanced the basal expression of
      TRPV4 and protected RAW264.7 cells from oxLDL-induced TRPV4 down-regulation.
      CONCLUSIONS: This study revealed that TRPV4 was widely expressed in macrophages
      and that oxLDL could induce the down-regulation of TRPV4 expression through its
      actions on PPARgamma. This study may serve as an important first step for further
      investigation into the roles of TRPV4 in macrophage-derived foam cell formation
      in atherosclerosis.

PMID- 27706113
TI  - Multinucleate cell angiohistiocytoma of the lower vermilion lip: an unusual site.
AB  - Multinucleate cell angiohistiocytoma (MCA) represent an uncommon benign
      fibrohistiocytic vascular lesion that sometimes may go undiagnosed because of its
      clinical and hystopathological similarities with benign fibrous histiocytoma and
      other soft-tissue neoplasms especially when localized on oral cavity or semi
      mucosa. We report the case of a solitary multinucleate cell angiohistiocytoma on
      the lower lip of a 46-year old woman suggesting that this rare lesion should be
      considered in the differential diagnosis of the oral soft-tissue neoplasms.

PMID- 27706111
TI  - Downregulation of Enhancer of Zeste Homolog 2 (EZH2) is essential for the
      Induction of Autophagy and Apoptosis in Colorectal Cancer Cells.
AB  - Increasing evidence indicates that elevated expression of enhancer of zeste
      homolog 2 gene (EZH2) in many human malignant tumors acts a significant role in
      the oncogenic process. However, the underlying molecular mechanism is still
      unclarified. It is evident that apoptosis and autophagy of tumor cells is crucial
      for the tumorigenesis and progression of cancer, however, the exact role of EZH2
      plays in apoptosis and autophagy has not been fully elucidated in colorectal
      cancer (CRC). Our previous study found that the expression level of EZH2 was
      higher in CRC tumor tissues than in the paired normal tissues using
      immunohistochemical analysis. We also recently found that the autophagy-related
      gene-related protein Ambra1 plays an important role in the autophagy pathway in
      CRC cells. In this study, mRNA and protein expression of EZH2 in four CRC cell
      lines were tested at first and RKO and HCT116 cells showed the highest levels
      among them. Here we transfected with EZH2-shRNA, or added DZNep (an EZH2
      inhibitor) to RKO and HCT116 cells in order to detect the effect of EZH2 on
      autophagy via determining the change of the protein expression of LC3 and Ambra1.
      The outcome indicated an obvious decrease of autophagy level in cells transfected
      with EZH2-shRNA or DZNep. We also found the apoptotic rate of cells was elevated
      significantly after downregulation of EZH2. In addition, compared to control
      group, CRC cells transfected with EZH2-shRNA or added DZNep revealed a
      significantly increased G1 cell cycle rate and an obvious decrease in the G2 cell
      cycle rate. Further analysis showed that knockdown of EZH2 induced cell-cycle
      arrest in CRC cells. Meanwhile, downregulation of EZH2 in CRC cells induces
      autophagy and apoptosis. Taken together, our results suggest that EZH2 plays a
      critical role in autophagy and apoptosis in the progression of CRC, which
      potentially facilitates the development of an ideal strategy for combating
      colorectal cancer.

PMID- 27706114
TI  - Antibodies against antigens related to scleroderma in a cohort of patients with
      morphea.
AB  - BACKGROUND: Morphea is a rare fibrosing skin disorder. Antinuclear antibodies
      (ANA), anti-histone and rheumatoid factor are detected in high rate of morphea
      cases. Scleroderma-related antibodies are usually absent. METHODS: Twenty-one
      adult patients affected by morphea were examined at the time of enrollment and
      after 6 months with the assessment of clinical outcome measures of disease
      severity and damage. Healthy subjects were considered as normal controls while
      patients affected by systemic sclerosis and other connective tissue diseases
      (CTD) were considered as pathological controls. Serum samples from all the
      patients and controls were analyzed for the detection of ANA, anti-nucleosome
      antibodies, anti-dsDNA and anti-extractable nuclear antigen. Scleroderma-related
      autoantibodies were searched using a line-blot test. RESULTS: We enrolled 21
      patients affected by morphea. ANA were found in 12 patients (57%). Anti-DNA and
      anti-nucleosome antibodies were negative in all cases. Systemic sclerosis
      specific antibodies were found in 11 morphea patients (52.4%) and one healthy
      control (6.25%). In patients affected by systemic sclerosis (100%) and different
      CTD (%), scleroderma-related autoantibodies were more frequently detected than in
      morphea (52.4%). In morphea, anti-TRIM21/Ro52 antibodies were found in 4 patients
      (36.4%) and resulted to be the most frequently detected antibodies also in two
      groups of SSC and CTD. CONCLUSIONS: The high prevalence of ANA and the
      identification of some antagonists of systemic sclerosis-related autoantibodies,
      confirm the idea of a significant activation of autoimmune system in morphea.

PMID- 27706110
TI  - Zoonotic Hepatitis E Virus: Classification, Animal Reservoirs and Transmission
      Routes.
AB  - During the past ten years, several new hepatitis E viruses (HEVs) have been
      identified in various animal species. In parallel, the number of reports of
      autochthonous hepatitis E in Western countries has increased as well, raising the
      question of what role these possible animal reservoirs play in human infections.
      The aim of this review is to present the recent discoveries of animal HEVs and
      their classification within the Hepeviridae family, their zoonotic and species
      barrier crossing potential, and possible use as models to study hepatitis E
      pathogenesis. Lastly, this review describes the transmission pathways identified
      from animal sources.

PMID- 27706115
TI  - Childhood psoriasis: a survey among pediatricians in Italy.
AB  - BACKGROUND: Psoriasis is one of the most common inflammatory skin diseases. There
      seem to be an increasing interest in childhood psoriasis in recent years.
      METHODS: We conducted a survey among pediatricians in Italy. 50 pediatricians
      from different areas in Italy (north, center and south) were invited to
      participate, 37 were responding and active in data collection. Doctors were asked
      to review their databases and to fill a form providing a series of information
      about all patients diagnosed with psoriasis attending their ambulatory. RESULTS:
      The total number of patients referring to the responding doctors was 28086. Of
      these, 66 were diagnosed with psoriasis. Mean age was 5.7, (6.3 in males and 5.1
      in females). The majority of patients presented plaque psoriasis (N.=44; 66.7%),
      followed by inverse (N.=9; 13.6%), and guttate psoriasis (N.=7; 10.6%). The main
      site of presentation was the trunk (51.5%), followed by scalp (15.2%) and napkin
      area (12.1%). Fifteen patients presented nail psoriasis (22.7%). In the majority
      of cases no family history was reported (83.3%), first degree relatives presented
      psoriatic lesions in only 7 cases (10.6%). The comorbidity most frequently
      reported was overweight (N.=16, 25.4%), followed by atopic dermatitis (N.=12;
      18.2%). Differences in the main pattern of presentation were found between male
      and female patients, in particular, a plaque type psoriasis was more frequent in
      males (79.4% vs. 53.1%; P=0.048). Female patients presented psoriasis of the
      napkin area more frequently than males (21.9% vs. 2.9%, P=0.025). CONCLUSIONS:
      Peculiar pattern of presentation can be detected in childhood psoriasis. Further
      studies are needed to validate these findings.

PMID- 27706116
TI  - Efficacy of the prophylactic administration of tramadol against postoperative
      shivering: a meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: Postoperative shivering (POS) is a common complication that occurs
      after regional and general anesthesia. Thus far, numerous studies have reported
      on the effectiveness of tramadol in preventing or treating POS. Here, we
      performed a meta-analysis to assess the efficacy of tramadol in the prevention of
      POS. EVIDENCE ACQUISTION: We systematically searched PubMed, Embase and the
      Cochrane Library to identify studies of the efficacy of tramadol in the
      prevention of POS. The results are expressed as relative ratios (RRs) and the
      corresponding 95% confidence intervals (CIs). EVIDENCE SYNTHESIS: Seventeen
      studies with a total of 1438 patients were included. Seven hundred seventy-seven
      of these patients received tramadol, and 661 received placebo. Compared with
      placebo, the patients who received tramadol exhibited a significant reduction in
      the incidence of POS based on subgroup analyses according to anesthesia (RR:
      0.27; 95% CI: 0.19-0.37; P<0.00001), different doses of tramadol (RR: 0.26; 95%
      CI: 0.19-0.35; P<0.00001), the rescue drug used (RR: 0.19; 95% CI: 0.10-0.35;
      P<0.00001) and the number of patients who experienced severe POS (RR: 0.17; 95%
      CI: 0.12-0.23; P<0.00001). Moreover, the administration of tramadol did not
      increase the risks of postoperative nausea and vomiting (PONV), hemodynamic
      turbulence, respiratory depression or deep sedation. CONCLUSIONS: This meta
      analysis revealed that prophylactic tramadol effectively prevents POS and reduces
      rescue medication use without significant adverse effects.

PMID- 27706117
TI  - The effect of routine availability of sugammadex on postoperative respiratory
      complications: a historical cohort study.
AB  - BACKGROUND: Postoperative residual curarisationf is a preventable cause of
      postoperative morbidity. Although sugammadex has been shown to reduce the risk of
      residual curarisation, it has not yet been shown if this directly translates to a
      reduction in morbidity. We aimed to demonstrate whether the introduction of
      unrestricted sugammadex for routine reversal changed the incidence of post
      operative respiratory diagnoses and the rate of airway and respiratory
      complications in the post-operative care unit. METHODS: A historical cohort study
      of 1257 patients who underwent general surgical or ear, nose and throat (ENT)
      procedures before and after the introduction of unrestricted availability of
      sugammadex. Patient records were used to identify the incidence of postoperative
      in-hospital respiratory diagnoses and of airway complications in PACU, the
      pattern of muscle relaxant use and the relative costs associated with the routine
      availability of sugammadex. RESULTS: Unrestricted sugammadex availability was
      associated with a significant reduction in the rate of a postoperative in
      hospital respiratory diagnosis; Odds Ratio (OR) = 0.20 (95%CI 0.05-0.72, p=0.01).
      Furthermore, the use of sugammadex itself was also associated with a reduction in
      inhospital respiratory diagnoses; OR = 0.26 (95%CI 0.08-0.94, p=0.04).
      Unrestricted sugammadex was also associated with a decrease in the need for
      manual airway support in the recovery room (3.2% vs 1.1%, p=0.02) and a decrease
      in patients being transferred intubated to ICU (5.5% vs 1.3%, p<0.001).
      CONCLUSION: Unrestricted sugammadex availability is associated with a reduction
      in post-operative respiratory complications. A well-designed, prospective
      randomised trial is needed to provide further validation of the data.

PMID- 27706118
TI  - Cervical facet joint syndrome: a possible cause of chronic cervicobrachial pain.

PMID- 27706119
TI  - Serum motilin levels and motilin gene polymorphisms in children with functional
      constipation.
AB  - BACKGROUND: Functional constipation is an important clinical problem among
      chidden all over the world. Its main cause is not completely understood. Motilin
      is a gastrointestinal hormone that increases intestinal motility. In this study,
      we aimed to investigate the serum motilin levels and its relationship with stool
      consistency and motilin gene polymorphisms in constipated children. METHODS: In
      this study we investigated 91 constipated patients (mean age 6.84 +/- 3.55 years)
      and 100 healthy controls (mean age 7.78 +/- 4.25 years). Serum motilin levels
      were assessed by sandwich enzyme-linked immunosorbent assay. rs2281820 (c.44 C>T)
      and rs2281818 (c.66 C>T) mutations were evaluated for motilin gene polymorphisms.
      RESULTS: Serum motilin levels were significantly lower in constipated children
      than healthy controls (6.20 +/- 7.86 pg/mL vs. 11.54 +/- 17.89 pg/mL,
      respectively, p=0.008). Serum motilin levels were significantly correlated with
      Bristol stool scale rate (r = 0.193, p= 0.011) in whole study group, but in the
      constipation group there was no significant correlation (r= - 0.072, p= 0.528).
      There were no differences in terms of presence or distribution of the
      polymorphisms of rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) in both groups.
      There was not a significant difference between different polymorphism groups
      regarding serum motilin concentrations in whole study group and also in both of
      the study groups. CONCLUSION: This study indicated for the first time that serum
      motilin levels decreased in constipated children. Further studies are needed to
      clarify whether motilin or motilin gene polymorphisms has a role in pathogenesis
      of functional constipation.

PMID- 27706121
TI  - Reaction to the sensory integration therapy in children with postural stability
      deficits.
AB  - BACKGROUND: The goal was to examine the influence of sensory integration therapy
      (SIT) on one leg standing in children with deficits of the postural stability.
      METHODS: 28 children 4 - 6 year old that could not stand on one leg for more than
      20 seconds were randomly divided into control "C" and experimental "E" groups.
      Group "C" participated in standard classes in the kindergarten. Group "E"
      participated in sensory integration therapy (SIT) for 2 weeks, 5 times a week
      (additionally to the standard classes). RESULTS: Results of the experiment show
      that the skill of standing on one leg has significantly improved (p<0.01) in the
      group that underwent additional therapy. The change in time of standing on the
      right leg with eyes open in the E group was statistically and significantly
      higher than the changes observed in the same time in group C (F = 22.5, p =
      0.001' eta2 = 0.44). Similarly, significant changes in time of standing on the
      right leg with eyes closed were observed in group E. The foregoing changes were
      bigger in group E than in group C (F = 16. 1 , p = 0.004, eta2 = 0.36). The
      analysis post hoc revealed that while there were no significant differences
      between the two groups on the pretest (p>0.05), there were significant
      differences between groups in right leg standing test with eyes open or closed on
      posttest. (p<0.05). Similar results were observed during on the one, left leg
      standing. The time of one leg standing with both eyes open and closed improved
      more significantly in group E than in group C (F = 20.4, p = 0.001, eta2 = 0.42
      respectively for the test with eyes open and F = 7.4, p = 0.010, eta2 = 0.21 for
      the test with eyes closed). The analysis post hoc revealed that while there were
      no significant differences between the two groups on the pretest (p>0.05), there
      were significant differences between groups in left leg standing test with eyes
      open or closed on posttest. (p<0.05). CONCLUSIONS: Research conducted show that
      there is a positive influence of SIT on children with low level of postural
      stability. Its significant improvement in children with low levels of postural
      stability is important not only for the current functioning of those children but
      for their future - by protecting them from falling down and from injuries.

PMID- 27706120
TI  - Effect of liposomes, vitamins A and E nasal spray in reducing the healing time
      after septoplasty with concurrent turbinate surgery in adolescents.
AB  - BACKGROUND: This study evaluates endoscopic and quality of life (QoL) outcomes in
      two groups, composed by both allergic (A) and non-allergic (N-A) adolescents
      undergoing septoplasty with concurrent turbinate surgery by radiofrequency
      treated after surgery with nasal spray containing liposomes and vitamins A and E.
      METHODS: This double-blind randomized study was carried out on 40 patients (22
      males, 18 females, mean age 15.5+/-1.0 years) undergoing septoplasty and
      volumetric tissue reduction of inferior turbinates by radiofrequency for post
      traumatic deformities and severe nasal obstruction. We enrolled 20 subjects with
      positive skin prick tests and 20 with negative skin prick tests (SPT) to
      aeroallergens. All subjects underwent the Visual Analogue Scale (VAS)
      questionnaire and the nasal endoscopy score by Lund and Kennedy (LK) at baseline
      before surgery (T0) and 15 days (T15) and 21 days (T21) after treatment. After
      surgery, the nose was not packed and the day after surgery all subjects were
      randomized into two groups, experimental arm group I (GI) and control arm group
      II (GII) and given the treatment, nasal spray containing liposomes composed of
      phospholipids, fatty acids, and vitamin A and E for group I and saline solution
      (sodium chloride 0.9%) for group II. RESULTS: After therapy, the VAS and LK
      scores were better (P<0.05) in the investigational than in the control arm in
      both sub-groups (A and N-A). CONCLUSIONS: Our findings suggested that liposomal,
      vitamins A and E nasal spray improves the QoL in the early postoperative period,
      both in A and N-A sub-groups.

PMID- 27706122
TI  - A systematic review of the association between allergic asthma and autism.
AB  - INTRODUCTION: Autism Spectrum Disorder represents a burdensome condition in early
      childhood, with a number of risk factors proposed to explain its pathogenesis,
      most of which without a reliable scientific basis. Allergic asthma is likely to
      be one of the possible comorbilities of autism. EVIDENCE ACQUISITION: In this
      paper, the relationship between autism and allergic asthma was analyzed through a
      systematic literature review, conducted according to the PRISMA Guidelines. The
      review was performed on PubMed and Science Direct database and covered the period
      January 1, 2004-July 9, 2016. The search was limited to articles published in
      peer-reviewed journals. The obtained results were sorted by relevance and the
      most significant case-control, epidemiological and nationwide-based works
      associating autism and allergic asthma in humans were selected. EVIDENCE
      SYNTHESIS: A slight correlation between these conditions has been found in more
      than a half studies selected, suggesting a possible association between the two
      diseases. Small sample sizes of some works and some methodological limitations
      rise uncertainty about this link. CONCLUSIONS: Autism Spectrum Disorder and
      asthma could be associated conditions, as evidenced by the higher prevalence of
      asthma in autistic children with respect to typically developed controls, with
      also a verisimilar biological basis. Despite that, future studies are required to
      provide more reliable data, also by employing animal models, to better clarify
      this, still unsure, relationship. Methods for study selection and inclusion
      criteria were specified in advance and documented in PROSPERO protocol
      #CRD42014012851.

PMID- 27706123
TI  - Non-invasive ultrasound measurements in male patients with LUTS and benign
      prostatic obstruction: implication for diagnosis and treatment.
AB  - BACKGROUND: To evaluate the role of the ultrasound assessments of the
      bladder/detrusor wall thickness (BWT/DWT) and the ultrasound estimated bladder
      weight (UEBW) in lower urinary tract symptoms diagnosis and treatment. EVIDENCE
      ACQUISITION: A systematic literature search from January 1995 until February 2016
      was performed on PubMed using the following terms: "bladder weight", "bladder
      wall thickness", "detrusor wall thickness", "LUTS", "bladder outlet obstruction"
      (BOO), "benign prostatic obstruction". Additional references were obtained from
      the reference list of full-text manuscripts. Abstracts presented at the annual
      congresses of the European Association of Urology, American Urology Association
      and the International Continence Society were also included. EVIDENCE SYNTHESIS:
      BWT and DWT are accurate predictors of BOO. Despite several differences in the
      technique assessment, population characteristics and study design, the BWT/DWT
      accuracy for BOO was close to 90%. Furthermore, the ultrasound evaluation of
      bladder/detrusor thickness correlates positively with symptoms score and the main
      clinical parameters in BPH patients. Lastly, BWT and DWT have proved to be
      optimal predictor of response to medical/surgical treatment of lower urinary
      tract symptoms/benign prostatic obstruction (LUTS/BPO). However, the lack of
      standardization among the available studies marks these methods promising but
      still experimental and further studies are needed to clarify the standard
      methodology. CONCLUSIONS: The ultrasound evaluation of bladder/detrusor thickness
      appears to be simple, highly accurate and non-invasive technique to predict BOO
      and to evaluate the clinical outcomes after medical/surgical treatments for
      LUTS/BPH. The implementation of these techniques and their standardization will
      probably better define their role in the diagnostic algorithms of patients with
      LUTS and possibly reduce the number of unnecessary pressure flow-studies.

PMID- 27706124
TI  - Comparison of GreenLight laser and transurethral resection of the prostate
      baseline characteristics and outcomes: lessons learned from the Clinical Research
      Office of the Endourological Society GreenLight Laser Study.
AB  - BACKGROUND: To compare baseline characteristics and outcomes of patients
      undergoing GreenLight laser vaporization (GL) or transurethral resection of the
      prostate (TURP) in a real life setting. METHODS: In this prospective
      observational cohort, the Clinical Research Office of the Endourological Society
      (CROES) collected data of consecutive GL or TURP treated patients. Treatment
      involved one of three GL laser powers (80 W, 120 W or 180 W) based on
      availability in each participating centre, or TURP. Data on baseline
      characteristics as well as functional measures were collected at three time
      points: 6-12 weeks, 6, and 12months after surgery. Functional measures included
      urinary flow parameters, perceived prostate function (IPSS), perceived erectile
      function (IIEF-5) and complications. RESULTS: Seven hundred thirteen patients
      underwent GL, and 234 patients underwent TURP. Overall, patients treated with GL
      show higher BMI, IIEF and medication use, together with lower urinary function
      (voided volume, incontinence, urinary retention) at baseline. After the
      procedure, despite higher antibiotic and antimuscarinic use and shorter hospital
      stay, readmission rates, PVR, PSA were higher, but Qmax, and IIEF were lower in
      the GL group. The rate of post-operative complications was 10.3% and 5.2% for the
      TURP and GL group, respectively (P=0.006). CONCLUSIONS: We were unable to
      categorically state which procedure is superior. This observational study
      confirms that treatment decision for either TURP or GL is not based on patient
      characteristics.

PMID- 27706125
TI  - The impact of nocturnal polyuria in older people with nocturnal LUTS.
AB  - BACKGROUND: Bladder dysfunctions often express the presence of lower urinary
      tract symptoms (LUTS) and are common in older people. The aim of this study was
      to analyze the micturition, incontinence and residual in older subjects,
      evaluating the role of nocturnal polyuria. METHODS: Eighty-six patients aged 65
      or older with invalidating LUTS were hospitalized for 24 hours. The maximum
      bladder capacity, mean micturition volume, post voiding residual and incontinence
      volume were recorded and analyzed day-time and night-time. Three groups were
      defined, i.e. nocturia, nocturnal incontinence and nocturnal polyuria (NP), and
      patients with or without NP were analyzed. RESULTS: With a majority of female
      patients 85% and a mean age of 74.3+/-5.96 years, a high incidence of nocturia
      (76%) was observed. NP was associated with nocturia in 56 patients (86%). In the
      three groups, the maximum bladder capacity and mean micturition volume were
      statistically higher during the night. Patients with nocturia or nocturnal
      incontinence associated to NP presented with a higher nocturnal maximum bladder
      capacity and mean micturition volume. A higher nocturnal post-void residual (PVR)
      was observed in patients with Nocturnal Incontinence associated with NP (P=0.03).
      Patients without NP presented significantly higher diurnal results. CONCLUSIONS:
      Nocturnal LUTS in older people is the result of a high nocturnal urine production
      related to NP with a higher nocturnal bladder capacity. The analyses of
      micturition, incontinence and PVR, and the accurate evaluation of the presence or
      absence of NP seems to be the key point for a better therapeutic choice in
      patients suffering by Nocturnal LUTS.

PMID- 27706127
TI  - Regulatory T cells decrease invariant natural killer T cell-mediated pregnancy
      loss in mice.
AB  - Pregnancy loss is the commonest complication of pregnancy. The causes of
      pregnancy loss are poorly understood. It has been reported that stimulation of
      invariant natural killer T (iNKT) cells using alpha-galactosylceramide (alphaGC)
      induces pregnancy loss in mice. Here we investigated the mechanisms, especially
      the role of regulatory T (Treg) cells, in iNKT cell-mediated pregnancy loss. We
      found that injection of alphaGC rapidly induced fetal resorption, activated
      decidual iNKT cells, decreased the percentage of decidual Treg cells and their
      interleukin (IL)-10 and transforming growth factor (TGF)-beta production, and
      upregulated the levels of interferon (IFN)-gamma, tumor necrosis factor-alpha, IL
      4, and IL-10 in serum. Adoptive transfer of iNKT cells from wild-type (WT) and IL
      4-/- mice but not IFN-gamma-/- mice into alphaGC-treated iNKT cell-deficient
      Jalpha18-/- mice restored alphaGC-induced pregnancy loss. Adoptive transfer of
      Treg cells downregulated alpha-GC-induced pregnancy loss in WT mice. Finally, co
      culture with alphaGC-stimulated decidual iNKT cells decreased the production of
      IL-10 and TGF-beta in decidual Treg cells and inhibited their suppressive
      activity. These findings suggest that activation of iNKT cells induces pregnancy
      loss in mice in an IFN-gamma-dependent manner. In addition, inhibition of the
      function of decidual Treg cells has an important role in iNKT cell-mediated
      pregnancy loss.

PMID- 27706126
TI  - RORgammat, a multitask nuclear receptor at mucosal surfaces.
AB  - RORgammat is a nuclear hormone receptor that has followed an exponential success
      carrier. Its modest origins as an orphan receptor cloned from human pancreas
      blossomed within 15 years into a critical regulator of anti-microbial immunity
      and a major target in the fight against inflammatory pathologies. Here, I review
      its role as a transcription factor required for the generation of type 3 lymphoid
      cells, which induce the development of lymphoid tissues, provide resistance of
      epithelial stem cells to injury, maintain homeostasis with the symbiotic
      microbiota, orchestrate defense against extracellular microbes, and regulate
      allergic responses. RORgammat is also an intriguing molecule that is regulated by
      the circadian rhythm and includes cholesterol metabolites as ligands. RORgammat
      therefore links anti-microbial immunity with circadian rhythms and steroids, the
      logic of which remains to be understood.

PMID- 27706128
TI  - Age-related spontaneous lacrimal keratoconjunctivitis is accompanied by
      dysfunctional T regulatory cells.
AB  - In both humans and animal models, the development of Sjogren syndrome (SS) and
      non-SS keratoconjunctivitis sicca (KCS) increases with age. Here, we investigated
      the ocular surface and lacrimal gland (LG) phenotype of NOD.B10.H2b mice at 7-14,
      45-50, and 96-100 weeks. Aged mice develop increased corneal permeability, CD4+ T
      cell infiltration, and conjunctival goblet cell loss. Aged mice have LG atrophy
      with increased lymphocyte infiltration and inflammatory cytokine levels. An
      increase in the frequency of CD4+Foxp3+ T regulatory cells (Tregs) was observed
      with age in the cervical lymph node (CLN), spleen, and LG. These CD4+CD25+ cells
      lose suppressive ability, while maintaining expression of Foxp3 (forkhead box P3)
      and producing interleukin-17 (IL-17) and interferon-gamma (IFN-gamma). An
      increase of Foxp3+IL-17+ or Foxp3+IFN-gamma+ cells was observed in the LG and LG
      draining CLN. In adoptive transfer experiments, recipients of either purified
      Tregs or purified T effector cells from aged donors developed lacrimal
      keratoconjunctivitis, whereas recipients of young Tregs or young T effector cells
      failed to develop disease. Overall, these results suggest inflammatory cytokine
      producing CD4+Foxp3+ cells participate in the pathogenesis of age-related ocular
      surface disease.

PMID- 27706131
TI  - Where are the data?

PMID- 27706130
TI  - Evolution of surfactant therapy for respiratory distress syndrome: past, present,
      and future.
AB  - Respiratory distress syndrome (RDS) due to surfactant deficiency is the most
      common cause of respiratory failure in preterm infants. Tremendous progress has
      been made since the original description that surfactant deficiency is the major
      cause of RDS. Surfactant therapy has been extensively studied in preterm infants
      and has been shown to significantly decrease air leaks and neonatal and infant
      mortality. Synthetic and animal-derived surfactants from bovine as well as
      porcine origin have been evaluated in randomized controlled trials. Animal
      derived surfactants generally result in faster weaning of respiratory support,
      shorter duration of invasive ventilation, and decreased mortality when compared
      to first- or second-generation of synthetic surfactants, but some of the second
      generation synthetic surfactants are at least not inferior to the animal-derived
      surfactants. Using a higher initial dose of porcine derived surfactant may
      provide better outcomes when compared with using lower doses of bovine
      surfactants, likely, due to compositional difference and/or the dose. Third
      generation synthetic surfactant containing peptide analogs of surfactant protein
      B and C are currently being studied. Less invasive intra-tracheal surfactant
      administration techniques in spontaneously breathing neonate receiving
      noninvasive ventilator support are also being evaluated. In the present era,
      prophylactic surfactant is not recommended as it may increase the risk of lung
      injury or death. In the future, surfactants may be used as vector to deliver
      steroids, or used in combination with molecules, such as, recombinant Club Cell
      Protein-10 (rhCC-10) to improve pulmonary outcomes. Also, noninvasive surfactant
      administration techniques, such as aerosolization or atomization of surfactant
      may play a greater role in the future.

PMID- 27706129
TI  - Pediatric sickle cell disease: past successes and future challenges.
AB  - Once a fatal disease of childhood, more than 95% of patients born today with
      sickle cell disease (SCD) in developed countries are expected to survive into
      adulthood, largely because of improvements in supportive and preventive care
      (newborn screening, penicillin prophylaxis, transcranial Doppler (TCD)
      screening). Hydroxyurea (HU) therapy, the only oral medication currently
      available to prevent SCD complications, has become more widespread over the past
      20 y. The NHLBI recommends that HU be offered to all patients with HbSS beginning
      at 9 mo of age, and the recently published Abnormal TCD with Transfusions
      Changing to HU (TWiTCH) trial has shown HU as an acceptable alternative to
      transfusion therapy for patients at high risk of stroke. While hematopoietic stem
      cell transplant (HSCT) is a curative option for SCD, less than 25% of patients
      have a suitable donor. Alternative stem cell sources from unrelated donors and
      haplo-identical donors are currently under investigation as are gene therapy
      trials. This review will focus on early efforts to elucidate SCD pathophysiology
      as well as supportive and preventive care improvements. Findings from recent
      multi-center studies (Silent Infarct Transfusion (SIT) Trial and TWiTCH) will be
      summarized. Finally, HSCT trials and gene therapy will be reviewed.

PMID- 27706132
TI  - Structural basis for the poisonous activity of a predator's venom insulin.

PMID- 27706133
TI  - Replicating methicillin resistance?

PMID- 27706134
TI  - De novo assembly and phasing of a Korean human genome.
AB  - Advances in genome assembly and phasing provide an opportunity to investigate the
      diploid architecture of the human genome and reveal the full range of structural
      variation across population groups. Here we report the de novo assembly and
      haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule
      real-time sequencing, next-generation mapping, microfluidics-based linked reads,
      and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule
      sequencing coupled with next-generation mapping generated a highly contiguous
      assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb,
      resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along
      with local assemblies and spanning long reads, closes 105 and extends into 72 out
      of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously
      intractable sequence. High concordance between the assembly and paired-end
      sequences from 62,758 BAC clones provides strong support for the robustness of
      the assembly. We identify 18,210 structural variants by direct comparison of the
      assembly with the human reference, identifying thousands of breakpoints that, to
      our knowledge, have not been reported before. Many of the insertions are
      reflected in the transcriptome and are shared across the Asian population. We
      performed haplotype phasing of the assembly with short reads, long reads and
      linked reads from whole-genome sequencing and with short reads from 31,719 BAC
      clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs
      assembled from single-molecule real-time reads assigned to haplotypes on phased
      blocks covered 89% of genes. The haplotigs accurately characterized the
      hypervariable major histocompatability complex region as well as demonstrating
      allele configuration in clinically relevant genes such as CYP2D6. This work
      presents the most contiguous diploid human genome assembly so far, with extensive
      investigation of unreported and Asian-specific structural variants, and high
      quality haplotyping of clinically relevant alleles for precision medicine.

PMID- 27706136
TI  - Evidence for a limit to human lifespan.
AB  - Driven by technological progress, human life expectancy has increased greatly
      since the nineteenth century. Demographic evidence has revealed an ongoing
      reduction in old-age mortality and a rise of the maximum age at death, which may
      gradually extend human longevity. Together with observations that lifespan in
      various animal species is flexible and can be increased by genetic or
      pharmaceutical intervention, these results have led to suggestions that longevity
      may not be subject to strict, species-specific genetic constraints. Here, by
      analysing global demographic data, we show that improvements in survival with age
      tend to decline after age 100, and that the age at death of the world's oldest
      person has not increased since the 1990s. Our results strongly suggest that the
      maximum lifespan of humans is fixed and subject to natural constraints.

PMID- 27706137
TI  - Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state.
AB  - The fin-to-limb transition represents one of the major vertebrate morphological
      innovations associated with the transition from aquatic to terrestrial life and
      is an attractive model for gaining insights into the mechanisms of morphological
      diversity between species. One of the characteristic features of limbs is the
      presence of digits at their extremities. Although most tetrapods have limbs with
      five digits (pentadactyl limbs), palaeontological data indicate that digits
      emerged in lobed fins of early tetrapods, which were polydactylous. How the
      transition to pentadactyl limbs occurred remains unclear. Here we show that the
      mutually exclusive expression of the mouse genes Hoxa11 and Hoxa13, which were
      previously proposed to be involved in the origin of the tetrapod limb, is
      required for the pentadactyl state. We further demonstrate that the exclusion of
      Hoxa11 from the Hoxa13 domain relies on an enhancer that drives antisense
      transcription at the Hoxa11 locus after activation by HOXA13 and HOXD13. Finally,
      we show that the enhancer that drives antisense transcription of the mouse Hoxa11
      gene is absent in zebrafish, which, together with the largely overlapping
      expression of hoxa11 and hoxa13 genes reported in fish, suggests that this
      enhancer emerged in the course of the fin-to-limb transition. On the basis of the
      polydactyly that we observed after expression of Hoxa11 in distal limbs, we
      propose that the evolution of Hoxa11 regulation contributed to the transition
      from polydactyl limbs in stem-group tetrapods to pentadactyl limbs in extant
      tetrapods.

PMID- 27706135
TI  - The epichaperome is an integrated chaperome network that facilitates tumour
      survival.
AB  - Transient, multi-protein complexes are important facilitators of cellular
      functions. This includes the chaperome, an abundant protein family comprising
      chaperones, co-chaperones, adaptors, and folding enzymes-dynamic complexes of
      which regulate cellular homeostasis together with the protein degradation
      machinery. Numerous studies have addressed the role of chaperome members in
      isolation, yet little is known about their relationships regarding how they
      interact and function together in malignancy. As function is probably highly
      dependent on endogenous conditions found in native tumours, chaperomes have
      resisted investigation, mainly due to the limitations of methods needed to
      disrupt or engineer the cellular environment to facilitate analysis. Such
      limitations have led to a bottleneck in our understanding of chaperome-related
      disease biology and in the development of chaperome-targeted cancer treatment.
      Here we examined the chaperome complexes in a large set of tumour specimens. The
      methods used maintained the endogenous native state of tumours and we exploited
      this to investigate the molecular characteristics and composition of the
      chaperome in cancer, the molecular factors that drive chaperome networks to
      crosstalk in tumours, the distinguishing factors of the chaperome in tumours
      sensitive to pharmacologic inhibition, and the characteristics of tumours that
      may benefit from chaperome therapy. We find that under conditions of stress, such
      as malignant transformation fuelled by MYC, the chaperome becomes biochemically
      'rewired' to form a network of stable, survival-facilitating, high-molecular
      weight complexes. The chaperones heat shock protein 90 (HSP90) and heat shock
      cognate protein 70 (HSC70) are nucleating sites for these physically and
      functionally integrated complexes. The results indicate that these tightly
      integrated chaperome units, here termed the epichaperome, can function as a
      network to enhance cellular survival, irrespective of tissue of origin or genetic
      background. The epichaperome, present in over half of all cancers tested, has
      implications for diagnostics and also provides potential vulnerability as a
      target for drug intervention.

PMID- 27706138
TI  - Ageing: Measuring our narrow strip of life.

PMID- 27706139
TI  - Cancer: A shocking protein complex.

PMID- 27706141
TI  - Erratum: Pore-forming activity and structural autoinhibition of the gasdermin
      family.

PMID- 27706140
TI  - Formation of new chromatin domains determines pathogenicity of genomic
      duplications.
AB  - Chromosome conformation capture methods have identified subchromosomal structures
      of higher-order chromatin interactions called topologically associated domains
      (TADs) that are separated from each other by boundary regions. By subdividing the
      genome into discrete regulatory units, TADs restrict the contacts that enhancers
      establish with their target genes. However, the mechanisms that underlie
      partitioning of the genome into TADs remain poorly understood. Here we show by
      chromosome conformation capture (capture Hi-C and 4C-seq methods) that genomic
      duplications in patient cells and genetically modified mice can result in the
      formation of new chromatin domains (neo-TADs) and that this process determines
      their molecular pathology. Duplications of non-coding DNA within the mouse Sox9
      TAD (intra-TAD) that cause female to male sex reversal in humans, showed
      increased contact of the duplicated regions within the TAD, but no change in the
      overall TAD structure. In contrast, overlapping duplications that extended over
      the next boundary into the neighbouring TAD (inter-TAD), resulted in the
      formation of a new chromatin domain (neo-TAD) that was isolated from the rest of
      the genome. As a consequence of this insulation, inter-TAD duplications had no
      phenotypic effect. However, incorporation of the next flanking gene, Kcnj2, in
      the neo-TAD resulted in ectopic contacts of Kcnj2 with the duplicated part of the
      Sox9 regulatory region, consecutive misexpression of Kcnj2, and a limb
      malformation phenotype. Our findings provide evidence that TADs are genomic
      regulatory units with a high degree of internal stability that can be sculptured
      by structural genomic variations. This process is important for the
      interpretation of copy number variations, as these variations are routinely
      detected in diagnostic tests for genetic disease and cancer. This finding also
      has relevance in an evolutionary setting because copy-number differences are
      thought to have a crucial role in the evolution of genome complexity.

PMID- 27706142
TI  - Metal-organic frameworks as selectivity regulators for hydrogenation reactions.
AB  - Owing to the limited availability of natural sources, the widespread demand of
      the flavouring, perfume and pharmaceutical industries for unsaturated alcohols is
      met by producing them from alpha,beta-unsaturated aldehydes, through the
      selective hydrogenation of the carbon-oxygen group (in preference to the carbon
      carbon group). However, developing effective catalysts for this transformation is
      challenging, because hydrogenation of the carbon-carbon group is
      thermodynamically favoured. This difficulty is particularly relevant for one
      major category of heterogeneous catalyst: metal nanoparticles supported on metal
      oxides. These systems are generally incapable of significantly enhancing the
      selectivity towards thermodynamically unfavoured reactions, because only the
      edges of nanoparticles that are in direct contact with the metal-oxide support
      possess selective catalytic properties; most of the exposed nanoparticle surfaces
      do not. This has inspired the use of metal-organic frameworks (MOFs) to
      encapsulate metal nanoparticles within their layers or inside their channels, to
      influence the activity of the entire nanoparticle surface while maintaining
      efficient reactant and product transport owing to the porous nature of the
      material. Here we show that MOFs can also serve as effective selectivity
      regulators for the hydrogenation of alpha,beta-unsaturated aldehydes. Sandwiching
      platinum nanoparticles between an inner core and an outer shell composed of an
      MOF with metal nodes of Fe3+, Cr3+ or both (known as MIL-101; refs 19, 20, 21)
      results in stable catalysts that convert a range of alpha,beta-unsaturated
      aldehydes with high efficiency and with significantly enhanced selectivity
      towards unsaturated alcohols. Calculations reveal that preferential interaction
      of MOF metal sites with the carbon-oxygen rather than the carbon-carbon group
      renders hydrogenation of the former by the embedded platinum nanoparticles a
      thermodynamically favoured reaction. We anticipate that our basic design strategy
      will allow the development of other selective heterogeneous catalysts for
      important yet challenging transformations.

PMID- 27706143
TI  - Corrigendum: Slowly fading super-luminous supernovae that are not pair
      instability explosions.

PMID- 27706144
TI  - Erratum: Pancreatic stellate cells support tumour metabolism through autophagic
      alanine secretion.

PMID- 27706145
TI  - Quantum dynamics of simultaneously measured non-commuting observables.
AB  - In quantum mechanics, measurements cause wavefunction collapse that yields
      precise outcomes, whereas for non-commuting observables such as position and
      momentum Heisenberg's uncertainty principle limits the intrinsic precision of a
      state. Although theoretical work has demonstrated that it should be possible to
      perform simultaneous non-commuting measurements and has revealed the limits on
      measurement outcomes, only recently has the dynamics of the quantum state been
      discussed. To realize this unexplored regime, we simultaneously apply two
      continuous quantum non-demolition probes of non-commuting observables to a
      superconducting qubit. We implement multiple readout channels by coupling the
      qubit to multiple modes of a cavity. To control the measurement observables, we
      implement a 'single quadrature' measurement by driving the qubit and applying
      cavity sidebands with a relative phase that sets the observable. Here, we use
      this approach to show that the uncertainty principle governs the dynamics of the
      wavefunction by enforcing a lower bound on the measurement-induced disturbance.
      Consequently, as we transition from measuring identical to measuring non
      commuting observables, the dynamics make a smooth transition from standard
      wavefunction collapse to localized persistent diffusion and then to isotropic
      persistent diffusion. Although the evolution of the state differs markedly from
      that of a conventional measurement, information about both non-commuting
      observables is extracted by keeping track of the time ordering of the measurement
      record, enabling quantum state tomography without alternating measurements. Our
      work creates novel capabilities for quantum control, including rapid state
      purification, adaptive measurement, measurement-based state steering and
      continuous quantum error correction. As physical systems often interact
      continuously with their environment via non-commuting degrees of freedom, our
      work offers a way to study how notions of contemporary quantum foundations arise
      in such settings.

PMID- 27706146
TI  - Characterisation of Reproduction-Associated Genes and Peptides in the Pest Land
      Snail, Theba pisana.
AB  - Increased understanding of the molecular components involved in reproduction may
      assist in understanding the evolutionary adaptations used by animals, including
      hermaphrodites, to produce offspring and retain a continuation of their lineage.
      In this study, we focus on the Mediterranean snail, Theba pisana, a
      hermaphroditic land snail that has become a highly invasive pest species within
      agricultural areas throughout the world. Our analysis of T. pisana CNS tissue has
      revealed gene transcripts encoding molluscan reproduction-associated proteins
      including APGWamide, gonadotropin-releasing hormone (GnRH) and an egg-laying
      hormone (ELH). ELH isoform 1 (ELH1) is known to be a potent reproductive peptide
      hormone involved in ovulation and egg-laying in some aquatic molluscs. Two other
      non-CNS ELH isoforms were also present in T. pisana (Tpi-ELH2 and Tpi-ELH3)
      within the snail dart sac and mucous glands. Bioactivity of a synthetic ELH1 on
      sexually mature T. pisana was confirmed through bioassay, with snails showing
      ELH1-induced egg-laying behaviours, including soil burrowing and oviposition. In
      summary, this study presents a detailed molecular analysis of reproductive
      neuropeptide genes in a land snail and provides a foundation for understanding
      ELH function.

PMID- 27706147
TI  - Spatiotemporal Dynamics and Fitness Analysis of Global Oil Market: Based on
      Complex Network.
AB  - We study the overall topological structure properties of global oil trade
      network, such as degree, strength, cumulative distribution, information entropy
      and weight clustering. The structural evolution of the network is investigated as
      well. We find the global oil import and export networks do not show typical scale
      free distribution, but display disassortative property. Furthermore, based on the
      monthly data of oil import values during 2005.01-2014.12, by applying random
      matrix theory, we investigate the complex spatiotemporal dynamic from the country
      level and fitness evolution of the global oil market from a demand-side analysis.
      Abundant information about global oil market can be obtained from deviating
      eigenvalues. The result shows that the oil market has experienced five different
      periods, which is consistent with the evolution of country clusters. Moreover, we
      find the changing trend of fitness function agrees with that of gross domestic
      product (GDP), and suggest that the fitness evolution of oil market can be
      predicted by forecasting GDP values. To conclude, some suggestions are provided
      according to the results.

PMID- 27706148
TI  - Calcium Stimulates Self-Assembly of Protein Kinase C alpha In Vitro.
AB  - Protein kinase C alpha (PKCalpha) is a nodal regulator in several intracellular
      signaling networks. PKCalpha is composed of modular domains that interact with
      each other to dynamically regulate spatial-temporal function. We find that
      PKCalpha specifically, rapidly and reversibly self-assembles in the presence of
      calcium in vitro. This phenomenon is dependent on, and can be modulated by an
      intramolecular interaction between the C1a and C2 protein domains of PKCalpha.
      Next, we monitor self-assembly of PKC-mCitrine fusion proteins using time
      resolved and steady-state homoFRET. HomoFRET between full-length PKCalpha
      molecules is observed when in solution with both calcium and liposomes containing
      either diacylglycerol (DAG) or phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2).
      Surprisingly, the C2 domain is sufficient to cluster on liposomes containing
      PI(4,5)P2, indicating the C1a domain is not required for self-assembly in this
      context. We conclude that three distinct clustered states of PKCalpha can be
      formed depending on what combination of cofactors are bound, but Ca2+ is
      minimally required and sufficient for clustering.

PMID- 27706149
TI  - Influenza Pandemics and Tuberculosis Mortality in 1889 and 1918: Analysis of
      Historical Data from Switzerland.
AB  - BACKGROUND: Tuberculosis (TB) mortality declined in the northern hemisphere over
      the last 200 years, but peaked during the Russian (1889) and the Spanish (1918)
      influenza pandemics. We studied the impact of these two pandemics on TB
      mortality. METHODS: We retrieved historic data from mortality registers for the
      city of Bern and countrywide for Switzerland. We used Poisson regression models
      to quantify the excess pulmonary TB (PTB) mortality attributable to influenza.
      RESULTS: Yearly PTB mortality rates increased during both influenza pandemics.
      Monthly influenza and PTB mortality rates peaked during winter and early spring.
      In Bern, for an increase of 100 influenza deaths (per 100,000 population) monthly
      PTB mortality rates increased by a factor of 1.5 (95%Cl 1.4-1.6, p<0.001) during
      the Russian, and 3.6 (95%Cl 0.7-18.0, p = 0.13) during the Spanish pandemic.
      Nationally, the factor was 2.0 (95%Cl 1.8-2.2, p<0.001) and 1.5 (95%Cl 1.1-1.9, p
      = 0.004), respectively. We did not observe any excess cancer or extrapulmonary TB
      mortality (as a negative control) during the influenza pandemics. CONCLUSIONS: We
      demonstrate excess PTB mortality during historic influenza pandemics in
      Switzerland, which supports a role for influenza vaccination in PTB patients in
      high TB incidence countries.

PMID- 27706150
TI  - Immediate Blood Draw for CD4+ Cell Count Is Associated with Linkage to Care in
      Durban, South Africa: Findings from Pathways to Engagement in HIV Care.
AB  - BACKGROUND: Timely linkage to care by newly-diagnosed HIV+ individuals remains a
      significant challenge to achieving UNAIDS 90-90-90 goals. Current World Health
      Organization (WHO) guidelines recommend initiating anti-retroviral treatment
      (ART) regardless of CD4+ count, with priority given to those with CD4+ <350
      cells/MUl. We evaluated the impact of not having a day-of-diagnosis CD4+ count
      blood draw, as recommended by South African guidelines, on time to linkage, using
      data from a prospective cohort study. METHODS: Individuals (N = 2773) were
      interviewed prior to HIV counseling and testing at three public sector primary
      care clinics in the greater Durban area; 785 were newly-diagnosed and eligible
      for the cohort study; 459 (58.5%) joined and were followed for eight months with
      three structured assessments. Linkage to care, defined as returning to clinic for
      CD4+ count results, and day-of-diagnosis blood draw were self-reported. RESULTS:
      Overall, 72.5% did not have a day-of-diagnosis CD4+ count blood draw, and 19.2%
      of these never returned. Compared with a day-of-diagnosis blood draw, the
      adjusted hazard ratio of linkage (AHRlinkage) associated with not having day-of
      diagnosis blood draw was 0.66 (95%CI: 0.51, 0.85). By 4 months, 54.8% of those
      without day-of-diagnosis blood draw vs. 75.2% with one were linked to care (chi
      squared p = 0.004). Of those who deferred blood draw, 48.3% cited clinic-related
      and 51.7% cited personal reasons. AHRlinkage was 0.60 (95%CI: 0.44, 0.82) for
      clinic-related and 0.53 (95%CI: 0.38, 0.75) for personal reasons relative to
      having day-of-diagnosis blood draw. CONCLUSIONS: Newly-diagnosed HIV+ individuals
      who did not undergo CD4+ count blood draw on the day they were diagnosed
      regardless of the reason for deferring-had delayed linkage to care relative to
      those with same-day blood draw. To enhance prompt linkage to care even when test
      and treat protocols are implemented, all diagnostic testing required before ART
      initiation should be performed on the same day as HIV testing/diagnosis. This may
      require modifying clinic procedures to enable overnight blood storage if same-day
      draws cannot be performed, and providing additional counseling to encourage newly
      diagnosed individuals to complete day-of-diagnosis testing. Tracking HIV+
      individuals via clinic registries should commence immediately from diagnosis to
      reduce these early losses to care.

PMID- 27706151
TI  - Mechanism of Rifampicin Inactivation in Nocardia farcinica.
AB  - A novel mechanism of rifampicin (Rif) resistance has recently been reported in
      Nocardia farcinica. This new mechanism involves the activity of rifampicin
      monooxygenase (RifMO), a flavin-dependent monooxygenase that catalyzes the
      hydroxylation of Rif, which is the first step in the degradation pathway.
      Recombinant RifMO was overexpressed and purified for biochemical analysis.
      Kinetic characterization revealed that Rif binding is necessary for effective FAD
      reduction. RifMO exhibits only a 3-fold coenzyme preference for NADPH over NADH.
      RifMO catalyzes the incorporation of a single oxygen atom forming an unstable
      intermediate that eventually is converted to 2'-N-hydroxy-4-oxo-Rif. Stable C4a
      hydroperoxyflavin was not detected by rapid kinetics methods, which is consistent
      with only 30% of the activated oxygen leading to product formation. These
      findings represent the first reported detailed biochemical characterization of a
      flavin-monooxygenase involved in antibiotic resistance.

PMID- 27706153
TI  - Critical Decline of the Eastern Caribbean Sperm Whale Population.
AB  - Sperm whale (Physeter macrocephalus) populations were expected to rebuild
      following the end of commercial whaling. We document the decline of the
      population in the eastern Caribbean by tracing demographic changes of well
      studied social units. We address hypotheses that, over a ten-year period of
      dedicated effort (2005-2015), unit size, numbers of calves and/or calving rates
      have each declined. Across 16 units, the number of adults decreased in 12 units,
      increased in two, and showed no change in two. The number of adults per unit
      decreased at -0.195 individuals/yr (95% CI: -0.080 to -0.310; P = 0.001). The
      number of calves also declined, but the decline was not significant. This
      negative trend of -4.5% per year in unit size started in about 2010, with numbers
      being fairly stable until then. There are several natural and anthropogenic
      threats, but no well-substantiated cause for the decline.

PMID- 27706152
TI  - The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in
      Extra-Pulmonary and Pulmonary Tuberculosis.
AB  - BACKGROUND: Mycobacterium tuberculosis infection is a leading cause of infectious
      death worldwide. Gene-expression microarray studies profiling the blood
      transcriptional response of tuberculosis (TB) patients have been undertaken in
      order to better understand the host immune response as well as to identify
      potential biomarkers of disease. To date most of these studies have focused on
      pulmonary TB patients with gene-expression profiles of extra-pulmonary TB
      patients yet to be compared to those of patients with pulmonary TB or
      sarcoidosis. METHODS: A novel cohort of patients with extra-pulmonary TB and
      sarcoidosis was recruited and the transcriptional response of these patients
      compared to those with pulmonary TB using a variety of transcriptomic approaches
      including testing a previously defined 380 gene meta-signature of active TB.
      RESULTS: The 380 meta-signature broadly differentiated active TB from healthy
      controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The
      top 15 genes from this meta-signature had a lower sensitivity for differentiating
      extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found
      the blood transcriptional responses in pulmonary and extra-pulmonary TB to be
      heterogeneous and to reflect the extent of symptoms of disease. CONCLUSIONS: The
      transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of
      gene expression reflective of symptom status, while the signature of pulmonary TB
      was distinct, based on a higher proportion of symptomatic individuals. These
      findings are of importance for the rational design and implementation of mRNA
      based TB diagnostics.

PMID- 27706154
TI  - Volunteer Conservation Action Data Reveals Large-Scale and Long-Term Negative
      Population Trends of a Widespread Amphibian, the Common Toad (Bufo bufo).
AB  - Rare and threatened species are the most frequent focus of conservation science
      and action. With the ongoing shift from single-species conservation towards the
      preservation of ecosystem services, there is a greater need to understand
      abundance trends of common species because declines in common species can
      disproportionately impact ecosystems function. We used volunteer-collected data
      in two European countries, the United Kingdom (UK) and Switzerland, since the
      1970s to assess national and regional trends for one of Europe's most abundant
      amphibian species, the common toad (Bufo bufo). Millions of toads were moved by
      volunteers across roads during this period in an effort to protect them from road
      traffic. For Switzerland, we additionally estimated trends for the common frog
      (Rana temporaria), a similarly widespread and common amphibian species. We used
      state-space models to account for variability in detection and effort and
      included only populations with at least 5 years of data; 153 populations for the
      UK and 141 for Switzerland. Common toads declined continuously in each decade in
      both countries since the 1980s. Given the declines, this common species almost
      qualifies for International Union for the Conservation of Nature (IUCN) red
      listing over this period despite volunteer conservation efforts. Reasons for the
      declines and wider impacts remain unknown. By contrast, common frog populations
      were stable or increasing in Switzerland, although there was evidence of declines
      after 2003. "Toads on Roads" schemes are vital citizen conservation action
      projects, and the data from such projects can be used for large scale trend
      estimations of widespread amphibians. We highlight the need for increased
      research into the status of common amphibian species in addition to conservation
      efforts focusing on rare and threatened species.

PMID- 27706155
TI  - AlignerBoost: A Generalized Software Toolkit for Boosting Next-Gen Sequencing
      Mapping Accuracy Using a Bayesian-Based Mapping Quality Framework.
AB  - Accurate mapping of next-generation sequencing (NGS) reads to reference genomes
      is crucial for almost all NGS applications and downstream analyses. Various
      repetitive elements in human and other higher eukaryotic genomes contribute in
      large part to ambiguously (non-uniquely) mapped reads. Most available NGS
      aligners attempt to address this by either removing all non-uniquely mapping
      reads, or reporting one random or "best" hit based on simple heuristics. Accurate
      estimation of the mapping quality of NGS reads is therefore critical albeit
      completely lacking at present. Here we developed a generalized software toolkit
      "AlignerBoost", which utilizes a Bayesian-based framework to accurately estimate
      mapping quality of ambiguously mapped NGS reads. We tested AlignerBoost with both
      simulated and real DNA-seq and RNA-seq datasets at various thresholds. In most
      cases, but especially for reads falling within repetitive regions, AlignerBoost
      dramatically increases the mapping precision of modern NGS aligners without
      significantly compromising the sensitivity even without mapping quality filters.
      When using higher mapping quality cutoffs, AlignerBoost achieves a much lower
      false mapping rate while exhibiting comparable or higher sensitivity compared to
      the aligner default modes, therefore significantly boosting the detection power
      of NGS aligners even using extreme thresholds. AlignerBoost is also SNP-aware,
      and higher quality alignments can be achieved if provided with known SNPs.
      AlignerBoost's algorithm is computationally efficient, and can process one
      million alignments within 30 seconds on a typical desktop computer. AlignerBoost
      is implemented as a uniform Java application and is freely available at
      https://github.com/Grice-Lab/AlignerBoost.

PMID- 27706156
TI  - Validation of a Rapid Rabies Diagnostic Tool for Field Surveillance in Developing
      Countries.
AB  - BACKGROUND: One root cause of the neglect of rabies is the lack of adequate
      diagnostic tests in the context of low income countries. A rapid, performance
      friendly and low cost method to detect rabies virus (RABV) in brain samples will
      contribute positively to surveillance and consequently to accurate data
      reporting, which is presently missing in the majority of rabies endemic
      countries. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated a rapid immunodiagnostic
      test (RIDT) in comparison with the standard fluorescent antibody test (FAT) and
      confirmed the detection of the viral RNA by real time reverse transcription
      polymerase chain reaction (RT-qPCR). Our analysis is a multicentre approach to
      validate the performance of the RIDT in both a field laboratory (N'Djamena, Chad)
      and an international reference laboratory (Institut Pasteur, Paris, France). In
      the field laboratory, 48 samples from dogs were tested and in the reference
      laboratory setting, a total of 73 samples was tested, representing a wide
      diversity of RABV in terms of animal species tested (13 different species),
      geographical origin of isolates with special emphasis on Africa, and different
      phylogenetic clades. Under reference laboratory conditions, specificity was 93.3%
      and sensitivity was 95.3% compared to the gold standard FAT test. Under field
      laboratory conditions, the RIDT yielded a higher reliability than the FAT test
      particularly on fresh and decomposed samples. Viral RNA was later extracted
      directly from the test filter paper and further used successfully for sequencing
      and genotyping. CONCLUSION/SIGNIFICANCE: The RIDT shows excellent performance
      qualities both in regard to user friendliness and reliability of the result. In
      addition, the test cassettes can be used as a vehicle to ship viral RNA to
      reference laboratories for further laboratory confirmation of the diagnosis and
      for epidemiological investigations using nucleotide sequencing. The potential for
      satisfactory use in remote locations is therefore very high to improve the global
      knowledge of rabies epidemiology. However, we suggest some changes to the
      protocol, as well as careful further validation, before promotion and wider use.

PMID- 27706157
TI  - Differential Infectivities among Different Japanese Encephalitis Virus Genotypes
      in Culex quinquefasciatus Mosquitoes.
AB  - During the last 20 years, the epidemiology of Japanese encephalitis virus (JEV)
      has changed significantly in its endemic regions due to the gradual displacement
      of the previously dominant genotype III (GIII) with clade b of GI (GI-b). Whilst
      there is only limited genetic difference distinguishing the two GI clades (GI-a
      and GI-b), GI-b has shown a significantly wider and more rapid dispersal pattern
      in several regions in Asia than the GI-a clade, which remains restricted in its
      geographic distribution since its emergence. Although previously published
      molecular epidemiological evidence has shown distinct phylodynamic patterns,
      characterization of the two GI clades has only been limited to in vitro studies.
      In this study, Culex quinquefasciatus, a known competent JEV mosquito vector
      species, was orally challenged with three JEV strains each representing GI-a, GI
      b, and GIII, respectively. Infection and dissemination were determined based on
      the detection of infectious viruses in homogenized mosquitoes. Detection of JEV
      RNA in mosquito saliva at 14 days post infection indicated that Cx.
      quinquefasciatus can be a competent vector species for both GI and GIII strains.
      Significantly higher infection rates in mosquitoes exposed to the GI-b and GIII
      strains than the GI-a strain suggest infectivity in arthropod vectors may lead to
      the selective advantage of previously and currently dominant genotypes. It could
      thus play a role in enzootic transmission cycles for the maintenance of JEV if
      this virus were ever to be introduced into North America.

PMID- 27706158
TI  - Colorimetric Detection of Plasmodium vivax in Urine Using MSP10 Oligonucleotides
      and Gold Nanoparticles.
AB  - Plasmodium vivax is the most prevalent cause of human malaria in the world and
      can lead to severe disease with high potential for relapse. Its genetic and
      geographic diversities make it challenging to control. P. vivax is understudied
      and to achieve control of malaria in endemic areas, a rapid, accurate, and simple
      diagnostic tool is necessary. In this pilot study, we found that a colorimetric
      system using AuNPs and MSP10 DNA detection in urine can provide fast, easy, and
      inexpensive identification of P. vivax. The test exhibited promising sensitivity
      (84%), high specificity (97%), and only mild cross-reactivity with P. falciparum
      (21%). It is simple to use, with a visible color change that negates the need for
      a spectrometer, making it suitable for use in austere conditions. Using urine
      eliminates the need for finger-prick, increasing both the safety profile and
      patient acceptance of this model.

PMID- 27706160
TI  - Sexual Dysfunction in Type 2 Diabetes at Diagnosis: Progression over Time and
      Drug and Non-Drug Correlated Factors.
AB  - AIMS: To present the longitudinal data of the SUBITO-DE study, a prospective
      survey involving male patients with new or recently diagnosed type 2 diabetes
      mellitus (T2DM) (<24 months). MATERIALS AND METHODS: Sexual function was assessed
      in male patients with T2DM at baseline (phase 1) and after a mean follow-up of 18
      months (phase 2). Standard metabolic parameters and sexual and depressive
      symptoms were evaluated. RESULTS: Six of the 499 enrolled patients died of
      different causes during phase 1. Of the 493 surviving men invited to participate
      in phase 2, 450 (mean age 59.0+/-9.0 years) (90.2%) accepted and 43 (8.2%) were
      lost to follow-up. As compared to baseline, the proportion of the men who
      reported improvement in erectile dysfunction (ED) at follow-up was nearly double
      that of the men who reported worsening of ED (22.6% vs. 12.8%). The increase in
      frequency of sexual activity the men reported at follow-up assessment indicates
      that many never treated before baseline were taking an ED drug during the study
      period (106 subjects). Phosphodiesterase type 5 inhibitors (PDE5i) were the ED
      drugs most commonly taken at both baseline and follow-up. An overall improvement
      over baseline values was observed in metabolic targets for T2DM and depressive
      symptoms. Conversely, no change in lifestyle behaviors was recorded during the
      study. CONCLUSIONS: Sexual dysfunction is a major concern in men with T2DM. The
      SUBITO-DE study demonstrates that, when combined with adequate counseling and
      tailored PDE5i therapy, an integrated approach to achieving metabolic targets in
      men with T2DM can improve sexual function as well as depressive symptoms.

PMID- 27706159
TI  - Molecular Detection of Tick-Borne Pathogens in Humans with Tick Bites and
      Erythema Migrans, in the Netherlands.
AB  - BACKGROUND: Tick-borne diseases are the most prevalent vector-borne diseases in
      Europe. Knowledge on the incidence and clinical presentation of other tick-borne
      diseases than Lyme borreliosis and tick-borne encephalitis is minimal, despite
      the high human exposure to these pathogens through tick bites. Using molecular
      detection techniques, the frequency of tick-borne infections after exposure
      through tick bites was estimated. METHODS: Ticks, blood samples and
      questionnaires on health status were collected from patients that visited their
      general practitioner with a tick bite or erythema migrans in 2007 and 2008. The
      presence of several tick-borne pathogens in 314 ticks and 626 blood samples of
      this cohort were analyzed using PCR-based methods. Using multivariate logistic
      regression, associations were explored between pathogens detected in blood and
      self-reported symptoms at enrolment and during a three-month follow-up period.
      RESULTS: Half of the ticks removed from humans tested positive for Borrelia
      burgdorferi sensu lato, Anaplasma phagocytophilum, Candidatus Neoehrlichia
      mikurensis, Rickettsia helvetica, Rickettsia monacensis, Borrelia miyamotoi and
      several Babesia species. Among 92 Borrelia burgdorferi s. l. positive ticks, 33%
      carried another pathogen from a different genus. In blood of sixteen out of 626
      persons with tick bites or erythema migrans, DNA was detected from Candidatus
      Neoehrlichia mikurensis (n = 7), Anaplasma phagocytophilum (n = 5), Babesia
      divergens (n = 3), Borrelia miyamotoi (n = 1) and Borrelia burgdorferi s. l. (n =
      1). None of these sixteen individuals reported any overt symptoms that would
      indicate a corresponding illness during the three-month follow-up period. No
      associations were found between the presence of pathogen DNA in blood and; self
      reported symptoms, with pathogen DNA in the corresponding ticks (n = 8), reported
      tick attachment duration, tick engorgement, or antibiotic treatment at enrolment.
      CONCLUSIONS: Based on molecular detection techniques, the probability of
      infection with a tick-borne pathogen other than Lyme spirochetes after a tick
      bite is roughly 2.4%, in the Netherlands. Similarly, among patients with erythema
      migrans, the probability of a co-infection with another tick-borne pathogen is
      approximately 2.7%. How often these infections cause disease symptoms or to what
      extend co-infections affect the course of Lyme borreliosis needs further
      investigations.

PMID- 27706161
TI  - Full Genome Sequence and sfRNA Interferon Antagonist Activity of Zika Virus from
      Recife, Brazil.
AB  - BACKGROUND: The outbreak of Zika virus (ZIKV) in the Americas has transformed a
      previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into
      a major public health concern. Little is currently known about the evolution and
      biology of ZIKV and the factors that contribute to the associated pathogenesis.
      Determining genomic sequences of clinical viral isolates and characterization of
      elements within these are an important prerequisite to advance our understanding
      of viral replicative processes and virus-host interactions. METHODOLOGY/PRINCIPAL
      FINDINGS: We obtained a ZIKV isolate from a patient who presented with classical
      ZIKV-associated symptoms, and used high throughput sequencing and other molecular
      biology approaches to determine its full genome sequence, including non-coding
      regions. Genome regions were characterized and compared to the sequences of other
      isolates where available. Furthermore, we identified a subgenomic flavivirus RNA
      (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced
      type I interferon induction, with a lesser effect on MDA-5 mediated action.
      CONCLUSIONS/SIGNIFICANCE: The full-length genome sequence including non-coding
      regions of a South American ZIKV isolate from a patient with classical symptoms
      will support efforts to develop genetic tools for this virus. Detection of sfRNA
      that counteracts interferon responses is likely to be important for further
      understanding of pathogenesis and virus-host interactions.

PMID- 27706162
TI  - Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation
      Strategies and Evidence of Their Success.
AB  - Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted
      since 2000 in Haiti, with a strong mass drug administration (MDA) program led by
      the Ministry of Public Health and Population and its collaborating international
      partners. By 2012, Haiti's neglected tropical disease (NTD) program had reached
      full national scale, and with such consistently good epidemiological coverage
      that it is now able to stop treatment for LF throughout almost all of the
      country. Essential to this success have been in the detail of how MDAs were
      implemented. These key programmatic elements included ensuring strong community
      awareness through an evidence-based, multi-channel communication and education
      campaign facilitated by voluntary drug distributors; strengthening community
      trust of the drug distributors by ensuring that respected community members were
      recruited and received appropriate training, supervision, identification, and
      motivation; enforcing a "directly observed treatment" strategy; providing easy
      access to treatment though numerous distribution posts and a strong drug supply
      chain; and ensuring quality data collection that was used to guide and inform MDA
      strategies. The evidence that these strategies were effective lies in both the
      high treatment coverage obtained- 100% geographical coverage reached in 2012,
      with almost all districts consistently achieving well above the epidemiological
      coverage targets of 65% for LF and 75% for STH-and the significant reduction in
      burden of infection- 45 communes having reached the target threshold for stopping
      treatment for LF. By taking advantage of sustained international financial and
      technical support, especially during the past eight years, Haiti's very
      successful MDA campaign resulted in steady progress toward LF elimination and
      development of a strong foundation for ongoing STH control. These efforts, as
      described, have not only helped establish the global portfolio of "best
      practices" for NTD control but also are poised to help solve two of the most
      important future NTD challenges-how to maintain control of STH infections after
      the community-based LF "treatment platform" ceases and how to ensure appropriate
      morbidity management for patients currently suffering from lymphatic filarial
      disease.

PMID- 27706163
TI  - A Motor-Gradient and Clustering Model of the Centripetal Motility of MTOCs in
      Meiosis I of Mouse Oocytes.
AB  - Asters nucleated by Microtubule (MT) organizing centers (MTOCs) converge on
      chromosomes during spindle assembly in mouse oocytes undergoing meiosis I. Time
      lapse imaging suggests that this centripetal motion is driven by a biased 'search
      and-capture' mechanism. Here, we develop a model of a random walk in a drift
      field to test the nature of the bias and the spatio-temporal dynamics of the
      search process. The model is used to optimize the spatial field of drift in
      simulations, by comparison to experimental motility statistics. In a second step,
      this optimized gradient is used to determine the location of immobilized dynein
      motors and MT polymerization parameters, since these are hypothesized to generate
      the gradient of forces needed to move MTOCs. We compare these scenarios to self
      organized mechanisms by which asters have been hypothesized to find the cell
      center- MT pushing at the cell-boundary and clustering motor complexes. By
      minimizing the error between simulation outputs and experiments, we find a model
      of "pulling" by a gradient of dynein motors alone can drive the centripetal
      motility. Interestingly, models of passive MT based "pushing" at the cortex,
      clustering by cross-linking motors and MT-dynamic instability gradients alone, by
      themselves do not result in the observed motility. The model predicts the
      sensitivity of the results to motor density and stall force, but not MTs per
      aster. A hybrid model combining a chromatin-centered immobilized dynein gradient,
      diffusible minus-end directed clustering motors and pushing at the cell cortex,
      is required to comprehensively explain the available data. The model makes
      experimentally testable predictions of a spatial bias and self-organized
      mechanisms by which MT asters can find the center of a large cell.

PMID- 27706164
TI  - Large Variations in HIV-1 Viral Load Explained by Shifting-Mosaic Metapopulation
      Dynamics.
AB  - The viral population of HIV-1, like many pathogens that cause systemic infection,
      is structured and differentiated within the body. The dynamics of cellular immune
      trafficking through the blood and within compartments of the body has also
      received wide attention. Despite these advances, mathematical models, which are
      widely used to interpret and predict viral and immune dynamics in infection,
      typically treat the infected host as a well-mixed homogeneous environment. Here,
      we present mathematical, analytical, and computational results that demonstrate
      that consideration of the spatial structure of the viral population within the
      host radically alters predictions of previous models. We study the dynamics of
      virus replication and cytotoxic T lymphocytes (CTLs) within a metapopulation of
      spatially segregated patches, representing T cell areas connected by circulating
      blood and lymph. The dynamics of the system depend critically on the interaction
      between CTLs and infected cells at the within-patch level. We show that for a
      wide range of parameters, the system admits an unexpected outcome called the
      shifting-mosaic steady state. In this state, the whole body's viral population is
      stable over time, but the equilibrium results from an underlying, highly dynamic
      process of local infection and clearance within T-cell centers. Notably, and in
      contrast to previous models, this new model can explain the large differences in
      set-point viral load (SPVL) observed between patients and their distribution, as
      well as the relatively low proportion of cells infected at any one time, and
      alters the predicted determinants of viral load variation.

PMID- 27706165
TI  - Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel
      Country.
AB  - An active search for Mycobacterium leprae drug resistance was carried out, 243
      multibacillary patients from endemic regions of Colombia were included from 2004
      to 2013 in a surveillance program. This program was a World Health Organization
      initiative for drug resistance surveillance in leprosy, where Colombia is a
      sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples
      was amplified and sequenced to identify mutations in the drug resistance
      determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible
      for rifampicin, dapsone and ofloxacin drug-resistance, respectively. Three
      isolates exhibited mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu,
      Ser458Met), two in the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate
      exhibited mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu),
      suggesting multidrug resistance. One isolate had a double mutation in folP1
      (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR that
      required in vivo evaluation of their association or not with drug resistance:
      rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and gyrA Ala107Leu.
      Seventy percent of M. leprae mutations were related to drug resistance and were
      isolated from relapsed patients; the likelihood of relapse was significantly
      associated with the presence of confirmed resistance mutations (OR range 20.1
      88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as
      a primary treatment. In summary, the current study calls attention to M. leprae
      resistance in Colombia, especially the significant association between confirmed
      resistance mutations and relapse in leprosy patients. A high frequency of DRDR
      mutations for rifampicin was seen in a region where dapsone monotherapy was used
      extensively.

PMID- 27706166
TI  - Metastable Features of Economic Networks and Responses to Exogenous Shocks.
AB  - It is well known that a network structure plays an important role in addressing a
      collective behavior. In this paper we study a network of firms and corporations
      for addressing metastable features in an Ising based model. In our model we
      observe that if in a recession the government imposes a demand shock to stimulate
      the network, metastable features shape its response. Actually we find that there
      exists a minimum bound where any demand shock with a size below it is unable to
      trigger the market out of recession. We then investigate the impact of network
      characteristics on this minimum bound. We surprisingly observe that in a Watts
      Strogatz network, although the minimum bound depends on the average of the
      degrees, when translated into the language of economics, such a bound is
      independent of the average degrees. This bound is about 0.44DeltaGDP, where
      DeltaGDP is the gap of GDP between recession and expansion. We examine our
      suggestions for the cases of the United States and the European Union in the
      recent recession, and compare them with the imposed stimulations. While the
      stimulation in the US has been above our threshold, in the EU it has been far
      below our threshold. Beside providing a minimum bound for a successful
      stimulation, our study on the metastable features suggests that in the time of
      crisis there is a "golden time passage" in which the minimum bound for successful
      stimulation can be much lower. Hence, our study strongly suggests stimulations to
      arise within this time passage.

PMID- 27706167
TI  - Quantifying Heterogeneity in Host-Vector Contact: Tsetse (Glossina swynnertoni
      and G. pallidipes) Host Choice in Serengeti National Park, Tanzania.
AB  - BACKGROUND: Identifying hosts of blood-feeding insect vectors is crucial in
      understanding their role in disease transmission. Rhodesian human African
      trypanosomiasis (rHAT), also known as acute sleeping sickness is caused by
      Trypanosoma brucei rhodesiense and transmitted by tsetse flies. The disease is
      commonly associated with wilderness areas of east and southern Africa. Such areas
      hold a diverse range of species which form communities of hosts for disease
      maintenance. The relative importance of different wildlife hosts remains unclear.
      This study quantified tsetse feeding preferences in a wilderness area of great
      host species richness, Serengeti National Park, Tanzania, assessing tsetse
      feeding and host density contemporaneously. METHODS: Glossina swynnertoni and G.
      pallidipes were collected from six study sites. Bloodmeal sources were identified
      through matching Cytochrome B sequences amplified from bloodmeals from recently
      fed flies to published sequences. Densities of large mammal species in each site
      were quantified, and feeding indices calculated to assess the relative selection
      or avoidance of each host species by tsetse. RESULTS: The host species most
      commonly identified in G. swynnertoni bloodmeals, warthog (94/220), buffalo
      (48/220) and giraffe (46/220), were found at relatively low densities (3-11/km2)
      and fed on up to 15 times more frequently than expected by their relative
      density. Wildebeest, zebra, impala and Thomson's gazelle, found at the highest
      densities, were never identified in bloodmeals. Commonly identified hosts for G.
      pallidipes were buffalo (26/46), giraffe (9/46) and elephant (5/46). CONCLUSIONS:
      This study is the first to quantify tsetse host range by molecular analysis of
      tsetse diet with simultaneous assessment of host density in a wilderness area.
      Although G. swynnertoni and G. pallidipes can feed on a range of species, they
      are highly selective. Many host species are rarely fed on, despite being present
      in areas where tsetse are abundant. These feeding patterns, along with the
      ability of key host species to maintain and transmit T. b. rhodesiense, drive the
      epidemiology of rHAT in wilderness areas.

PMID- 27706168
TI  - Unveiling the Hidden Bat Diversity of a Neotropical Montane Forest.
AB  - Mountain environments, characterized by high levels of endemism, are at risk of
      experiencing significant biodiversity loss due to current trends in global
      warming. While many acknowledge their importance and vulnerability, these
      ecosystems still remain poorly studied, particularly for taxa that are difficult
      to sample such as bats. Aiming to estimate the amount of cryptic diversity among
      bats of a Neotropical montane cloud forest in Talamanca Range-south-east Central
      America-, we performed a 15-night sampling campaign, which resulted in 90
      captured bats belonging to 8 species. We sequenced their mitochondrial cytochrome
      c oxidase subunit I (COI) and screened their inter- and intraspecific genetic
      variation. Phylogenetic relations with conspecifics and closely related species
      from other geographic regions were established using Maximum Likelihood and
      Bayesian inference methods, as well as median-joining haplotype networks.
      Mitochondrial lineages highly divergent from hitherto characterized populations
      (> 9% COI dissimilarity) were found in Myotis oxyotus and Hylonycteris
      underwoodi. Sturnira burtonlimi and M. keaysi also showed distinct mitochondrial
      structure with sibling species and/or populations. These results suggest that
      mountains in the region hold a high degree of endemicity potential that has
      previously been ignored in bats. They also warn of the high extinction risk
      montane bats may be facing due to climatic change, particularly in isolated
      mountain systems like Talamanca Range.

PMID- 27706169
TI  - Magnitude of Birth Defects in Central and Northwest Ethiopia from 2010-2014: A
      Descriptive Retrospective Study.
AB  - BACKGROUND: Birth defects are defined as structural and functional defects that
      develop during the organogenesis period and present at birth or detected later in
      life. They are one of the leading causes of infant and child mortality,
      morbidity, and long term disability. The magnitude of birth defects varies from
      country to country and from race/ethnicity to race/ethnicity, and about 40-60% of
      their causes are unknown. The known causes of birth defects are genetic and
      environmental factors which may be prevented. For various reasons, there is lack
      of data and research on birth defects in Ethiopia. OBJECTIVE: The major objective
      of this study is to estimate the magnitude of birth defects in Ethiopia. SUBJECT
      AND METHODS: A hospital based, retrospective, cross sectional, descriptive study
      was conducted. The subjects were babies/children aged 0-17years who visited
      selected hospitals between 2010 and 2014. Fourteen hospitals (8 in Addis Ababa, 6
      in Amhara Region) were selected purposively based on case load. A data retrieving
      form was developed to extract relevant information from record books. RESULTS: In
      the hospitals mentioned, 319,776 various medical records of children aged 0
      17years were found. Of these, 6,076 (1.9% with 95% CI: 1.85%-1.95%) children were
      diagnosed as having birth defects. The majority (58.5%) of the children were male
      and 41.5% female. A slightly more than half (51.1%) of the children were urban
      dwellers, while 48.9% were from rural areas. Among the participants of the study
      the proportion of birth defects ranged as follows: orofacial (34.2%), neural tube
      (30.8%), upper and lower limb (12.8%), cardiovascular system (10.3%), digestive
      system and abdominal wall (4.8%), unspecified congenital malformations (2.5%),
      Down syndrome (2%), genitourinary system (2%), head, face, and neck defects
      (0.4%), and others (0.3%). The trend of birth defects increased linearly over
      time [Extended Mantel-Haenszel chi square for linear trend = 356.7 (P<0.0001)].
      About 275 (4.5%) of the cases had multiple (associated) birth defects and 5,801
      (95.5%) isolated (single) birth defects. Out of the total birth defects, 6,018
      (99%) were major and 58 (1%) minor. CONCLUSION: The magnitude of birth defects
      increased from 2010-2014. Orofacial and neural tube defects contributed about two
      thirds of the birth defects. There is an urgent need for registry and
      surveillance system strategies for intervention and control of birth defects in
      Ethiopia.

PMID- 27706170
TI  - Retrospective Analysis of Serotype Switching of Vibrio cholerae O1 in a Cholera
      Endemic Region Shows It Is a Non-random Process.
AB  - Genomic data generated from clinical Vibrio cholerae O1 isolates collected over a
      five year period in an area of Kolkata, India with seasonal cholera outbreaks
      allowed a detailed genetic analysis of serotype switching that occurred from
      Ogawa to Inaba and back to Ogawa. The change from Ogawa to Inaba resulted from
      mutational disruption of the methyltransferase encoded by the wbeT gene. Re
      emergence of the Ogawa serotype was found to result either from expansion of an
      already existing Ogawa clade or reversion of the mutation in an Inaba clade. Our
      data suggests that such transitions are not random events but rather driven by as
      yet unidentified selection mechanisms based on differences in the structure of
      the O1 antigen or in the serotype-determining wbeT gene.

PMID- 27706171
TI  - The Eco-epidemiology of Pacific Coast Tick Fever in California.
AB  - Rickettsia philipii (type strain "Rickettsia 364D"), the etiologic agent of
      Pacific Coast tick fever (PCTF), is transmitted to people by the Pacific Coast
      tick, Dermacentor occidentalis. Following the first confirmed human case of PCTF
      in 2008, 13 additional human cases have been reported in California, more than
      half of which were pediatric cases. The most common features of PCTF are the
      presence of at least one necrotic lesion known as an eschar (100%), fever (85%),
      and headache (79%); four case-patients required hospitalization and four had
      multiple eschars. Findings presented here implicate the nymphal or larval stages
      of D. occidentalis as the primary vectors of R. philipii to people. Peak
      transmission risk from ticks to people occurs in late summer. Rickettsia philipii
      DNA was detected in D. occidentalis ticks from 15 of 37 California counties.
      Similarly, non-pathogenic Rickettsia rhipicephali DNA was detected in D.
      occidentalis in 29 of 38 counties with an average prevalence of 12.0% in adult
      ticks. In total, 5,601 ticks tested from 2009 through 2015 yielded an overall R.
      philipii infection prevalence of 2.1% in adults, 0.9% in nymphs and a minimum
      infection prevalence of 0.4% in larval pools. Although most human cases of PCTF
      have been reported from northern California, acarological surveillance suggests
      that R. philipii may occur throughout the distribution range of D. occidentalis.

PMID- 27706172
TI  - An Easy Phylogenetically Informative Method to Trace the Globally Invasive
      Potamopyrgus Mud Snail from River's eDNA.
AB  - Potamopyrgus antipodarum (New Zealand mud snail) is a prosobranch mollusk native
      to New Zealand with a wide invasive distribution range. Its non-indigenous
      populations are reported from Australia, Asia, Europe and North America. Being an
      extremely tolerant species, Potamopyrgus is capable to survive in a great range
      of salinity and temperature conditions, which explains its high invasiveness and
      successful spread outside the native range. Here we report the first finding of
      Potamopyrgus antipodarum in a basin of the Cantabrian corridor in North Iberia
      (Bay of Biscay, Spain). Two haplotypes already described in Europe were found in
      different sectors of River Nora (Nalon basin), suggesting the secondary
      introductions from earlier established invasive populations. To enhance the
      surveillance of the species and tracking its further spread in the region, we
      developed a specific set of primers for the genus Potamopyrgus that amplify a
      fragment of 16S rDNA. The sequences obtained from PCR on DNA extracted from
      tissue and water samples (environmental DNA, eDNA) were identical in each
      location, suggesting clonal reproduction of the introduced individuals. Multiple
      introduction events from different source populations were inferred from our
      sequence data. The eDNA tool developed here can serve for tracing New Zealand mud
      snail populations outside its native range, and for inventorying mud snail
      population assemblages in the native settings if high throughput sequencing
      methodologies are employed.

PMID- 27706173
TI  - A Complete Fossil-Calibrated Phylogeny of Seed Plant Families as a Tool for
      Comparative Analyses: Testing the 'Time for Speciation' Hypothesis.
AB  - Explaining the uneven distribution of species richness across the branches of the
      tree of life has been a major challenge for evolutionary biologists. Advances in
      phylogenetic reconstruction, allowing the generation of large, well-sampled,
      phylogenetic trees have provided an opportunity to contrast competing hypotheses.
      Here, we present a new time-calibrated phylogeny of seed plant families using
      Bayesian methods and 26 fossil calibrations. While there are various published
      phylogenetic trees for plants which have a greater density of species sampling,
      we are still a long way from generating a complete phylogeny for all ~300,000+
      plants. Our phylogeny samples all seed plant families and is a useful tool for
      comparative analyses. We use this new phylogenetic hypothesis to contrast two
      alternative explanations for differences in species richness among higher taxa:
      time for speciation versus ecological limits. We calculated net diversification
      rate for each clade in the phylogeny and assessed the relationship between clade
      age and species richness. We then fit models of speciation and extinction to
      individual branches in the tree to identify major rate-shifts. Our data suggest
      that the majority of lineages are diversifying very slowly while a few lineages,
      distributed throughout the tree, are diversifying rapidly. Diversification is
      unrelated to clade age, no matter the age range of the clades being examined,
      contrary to both the assumption of an unbounded lineage increase through time,
      and the paradigm of fixed ecological limits. These findings are consistent with
      the idea that ecology plays a role in diversification, but rather than imposing a
      fixed limit, it may have variable effects on per lineage diversification rates
      through time.

PMID- 27706174
TI  - The Performance of the Vaginal Discharge Syndromic Management in Treating Vaginal
      and Cervical Infection: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: This review aimed to synthesize and analyze the diagnostic accuracy
      and the likelihood of providing correct treatment of the syndromic approach
      Vaginal Discharge Flowchart in managing cervical infections caused by Neisseria
      gonorrhoeae (NG) and Chlamydia trachomatis (CT), and vaginal infections caused by
      Trichomonas vaginalis (TV) and Bacterial vaginosis (BV) and Candida albicans.
      This review will inform updating the WHO 2003 guidelines on Vaginal Discharge
      syndromic case management. METHODS: A systematic review was conducted on
      published studies from 01-01-2000 to 30-03-2015 in multiple databases. Studies
      evaluating the diagnostic accuracy and validation of the WHO Vaginal Discharge
      Flowchart were included. Validation parameters including sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      and the 95% confidence intervals for the different types of the flowchart were
      taken as outcomes, re-calculated, and analysed using a fixed model meta-analysis
      for data pooling. The level of agreement between the index and reference test
      were determined by the Cohen's Kappa co-efficiency test. Each individual study
      was assessed on quality using the QUADAS-2 tool. FINDINGS: The search yielded
      2,845 studies of which 16 met the eligibility criteria for final analysis. The
      diagnostic performance to identify cervical infections was low and resulted in a
      high proportion of over and missed treatment. The four flowcharts had a
      sensitivity between 27.37% in history and risk assessment and 90.13% with
      microscopy, with the inverse in specificity rates. The treatment performances
      between the flowcharts were inconsistent. The same applies to the use of vaginal
      discharge flowchart for treating vaginal infections. For vaginal infections the
      vaginal discharge flowchart had a good performance in flowchart 3 with 91.68% of
      sensitivity; 99.97% specificity; 99.93% PPV and 0.02% who missed their treatment
      and 8.32% of women who were over treated by the vaginal discharge flowchart.
      CONCLUSION: The vaginal discharge flowchart should focus on management of vaginal
      infection. It could be used as an intermediate approach for cervical infections
      for sex workers until a point of care test is available in resource poor
      settings.

PMID- 27706175
TI  - The Production of a Stable Infliximab Powder: The Evaluation of Spray and Freeze
      Drying for Production.
AB  - In prospect of developing an oral dosage form of Infliximab, for treatment of
      Crohn's disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays)
      and spray-drying were investigated as production method for stable powders.
      Dextran and inulin were used in combination with sucrose as stabilizing
      excipients. The drying processes did not affect Infliximab in these formulations,
      i.e. both the physical integrity and biological activity (TNF binding) were
      retained. Accelerated stability studies (1 month at 60 degrees C) showed that the
      TNF binding ability of Infliximab was conserved in the freeze-dried formulations,
      whereas the liquid counterpart lost all TNF binding. After thermal treatment, the
      dried formulations showed some chemical modification of the IgG in the dextran
      sucrose formulation, probably due to Maillard reaction products. This study
      indicates that, with the appropriate formulation, both spray-drying and freeze
      drying may be useful for (bulk) powder production of Infliximab.

PMID- 27706176
TI  - Sensitivity of Seven Diverse Species to Blue and Green Light: Interactions with
      Photon Flux.
AB  - Despite decades of research, the effects of spectral quality on plant growth, and
      development are not well understood. Much of our current understanding comes from
      studies with daily integrated light levels that are less than 10% of summer
      sunlight thus making it difficult to characterize interactions between light
      quality and quantity. Several studies have reported that growth is increased
      under fluorescent lamps compared to mixtures of wavelengths from LEDs.
      Conclusions regarding the effect of green light fraction range from detrimental
      to beneficial. Here we report the effects of eight blue and green light fractions
      at two photosynthetic photon fluxes (PPF; 200 and 500 MUmol m-2 s-1; with a daily
      light integral of 11.5 and 29 mol m-2 d-1) on growth (dry mass), leaf expansion,
      stem and petiole elongation, and whole-plant net assimilation of seven diverse
      plant species. The treatments included cool, neutral, and warm white LEDs, and
      combinations of blue, green and/or red LEDs. At the higher PPF (500), increasing
      blue light in increments from 11 to 28% reduced growth in tomato, cucumber, and
      pepper by 22, 26, and 14% respectively, but there was no statistically
      significant effect on radish, soybean, lettuce or wheat. At the lower PPF (200),
      increasing blue light reduced growth only in tomato (41%). The effects of blue
      light on growth were mediated by changes in leaf area and radiation capture, with
      minimal effects on whole-plant net-assimilation. In contrast to the significant
      effects of blue light, increasing green light in increments from 0 to 30% had a
      relatively small effect on growth, leaf area and net assimilation at either low
      or high PPF. Surprisingly, growth of three of the seven species was not reduced
      by a treatment with 93% green light compared to the broad spectrum treatments.
      Collectively, these results are consistent with a shade avoidance response
      associated with either low blue or high green light fractions.

PMID- 27706177
TI  - Real-Time Shear Wave versus Transient Elastography for Predicting Fibrosis:
      Applicability, and Impact of Inflammation and Steatosis. A Non-Invasive
      Comparison.
AB  - BACKGROUND AND AIMS: Real-time shear wave elastography (2D-SWE) is a two
      dimensional transient elastography and a competitor as a biomarker of liver
      fibrosis in comparison with the standard reference transient elastography by M
      probe (TE-M). The aims were to compare several criteria of applicability, and to
      assess inflammation and steatosis impact on elasticity values, two unmet needs.
      METHODS: We took FibroTest as the fibrosis reference and ActiTest and SteatoTest
      as quantitative estimates of inflammation and steatosis. After standardization of
      estimates, analyses used curve fitting, quantitative Lin concordance coefficient
      [LCC], and multivariate logistic regression. RESULTS: A total of 2,251
      consecutive patients were included. We validated the predetermined 0.2 kPa cut
      off as a too low minimal elasticity value identifying not-reliable 2D-SWE results
      (LCC with FibroTest = 0.0281[-0.119;0.175]. Other criteria, elasticity CV, body
      mass index and depth of measures were not sufficiently discriminant. The
      applicability of 2D-SWE (95%CI) 89.6%(88.2-90.8), was significantly higher than
      that of TE, 85.6%(84.0-87.0; P<0.0001). In patients with non-advanced fibrosis
      (METAVIR F0F1F2), elasticity values estimated by 2D-SWE was less impacted by
      inflammation and steatosis than elasticity value estimated by TE-M: LCC (95%CI)
      0.039 (0.021;0.058) vs 0.090 (0.068;0.112;P<0.01) and 0.105 (0.068;0.141) vs
      0.192 (0.153;0.230; P<0.01) respectively. The three analyses methods gave similar
      results. CONCLUSIONS: Elasticity results including very low minimal signal in the
      region of interest should be considered not reliable. 2D-SWE had a higher
      applicability than TE, the reference elastography, with less impact of
      inflammation and steatosis especially in patients with non-advanced fibrosis, as
      presumed by blood tests. TRIAL REGISTRATION: ClinicalTrials.gov NCT01927133.

PMID- 27706178
TI  - Habitat Discontinuities Separate Genetically Divergent Populations of a Rocky
      Shore Marine Fish.
AB  - Habitat fragmentation has been suggested to be responsible for major genetic
      differentiations in a range of marine organisms. In this study, we combined
      genetic data and environmental information to unravel the relative role of
      geography and habitat heterogeneity on patterns of genetic population structure
      of corkwing wrasse (Symphodus melops), a rocky shore species at the northern
      limit of its distribution range in Scandinavia. Our results revealed a major
      genetic break separating populations inhabiting the western and southern coasts
      of Norway. This genetic break coincides with the longest stretch of sand in the
      whole study area, suggesting habitat fragmentation as a major driver of genetic
      differentiation of this obligate rocky shore benthic fish in Scandinavia. The
      complex fjords systems extending along the western coast of Norway appeared
      responsible for further regional genetic structuring. Our findings indicate that
      habitat discontinuities may lead to significant genetic fragmentation over short
      geographical distances, even for marine species with a pelagic larval phase, as
      for this rocky shore fish.

PMID- 27706179
TI  - Noninvasive Imaging of Human Atrial Activation during Atrial Flutter and Normal
      Rhythm from Body Surface Potential Maps.
AB  - BACKGROUND: Knowledge of atrial electrophysiological properties is crucial for
      clinical intervention of atrial arrhythmias and the investigation of the
      underlying mechanism. This study aims to evaluate the feasibility of a novel
      noninvasive cardiac electrical imaging technique in imaging bi-atrial activation
      sequences from body surface potential maps (BSPMs). METHODS: The study includes 7
      subjects, with 3 atrial flutter patients, and 4 healthy subjects with normal
      atrial activations. The subject-specific heart-torso geometries were obtained
      from MRI/CT images. The equivalent current densities were reconstructed from 208
      channel BSPMs by solving the inverse problem using individual heart-torso
      geometry models. The activation times were estimated from the time instant
      corresponding to the highest peak in the time course of the equivalent current
      densities. To evaluate the performance, a total of 32 cycles of atrial flutter
      were analyzed. The imaged activation maps obtained from single beats were
      compared with the average maps and the activation maps measured from CARTO, by
      using correlation coefficient (CC) and relative error (RE). RESULTS: The cardiac
      electrical imaging technique is capable of imaging both focal and reentrant
      activations. The imaged activation maps for normal atrial activations are
      consistent with findings from isolated human hearts. Activation maps for isthmus
      dependent counterclockwise reentry were reconstructed on three patients with
      typical atrial flutter. The method was capable of imaging macro counterclockwise
      reentrant loop in the right atrium and showed inter-atria electrical conduction
      through coronary sinus. The imaged activation sequences obtained from single
      beats showed good correlation with both the average activation maps (CC = 0.91+/
      0.03, RE = 0.29+/-0.05) and the clinical endocardial findings using CARTO (CC =
      0.70+/-0.04, RE = 0.42+/-0.05). CONCLUSIONS: The noninvasive cardiac electrical
      imaging technique is able to reconstruct complex atrial reentrant activations and
      focal activation patterns in good consistency with clinical electrophysiological
      mapping. It offers the potential to assist in radio-frequency ablation of atrial
      arrhythmia and help defining the underlying arrhythmic mechanism.

PMID- 27706180
TI  - Commercial Plant Production and Consumption Still Follow the Latitudinal Gradient
      in Species Diversity despite Economic Globalization.
AB  - Increasing trade between countries and gains in income have given consumers
      around the world access to a richer and more diverse set of commercial plant
      products (i.e., foods and fibers produced by farmers). According to the economic
      theory of comparative advantage, countries open to trade will be able to consume
      more-in terms of volume and diversity-if they concentrate production on
      commodities that they can most cost-effectively produce, while importing goods
      that are expensive to produce, relative to other countries. Here, we perform a
      global analysis of traded commercial plant products and find little evidence that
      increasing globalization has incentivized agricultural specialization. Instead, a
      country's plant production and consumption patterns are still largely determined
      by local evolutionary legacies of plant diversification. Because tropical
      countries harbor a greater diversity of lineages across the tree of life than
      temperate countries, tropical countries produce and consume a greater diversity
      of plant products than do temperate countries. In contrast, the richer and more
      economically advanced temperate countries have the capacity to produce and
      consume more plant species than the generally poorer tropical countries, yet this
      collection of plant species is drawn from fewer branches on the tree of life. Why
      have countries not increasingly specialized in plant production despite the
      theoretical financial incentive to do so? Potential explanations include the
      persistence of domestic agricultural subsidies that distort production decisions,
      cultural preferences for diverse local food production, and that diverse food
      production protects rural households in developing countries from food price
      shocks. Less specialized production patterns will make crop systems more
      resilient to zonal climatic and social perturbations, but this may come at the
      expense of global crop production efficiency, an important step in making the
      transition to a hotter and more crowded world.

PMID- 27706181
TI  - The Relationship between the Bcl-2/Bax Proteins and the Mitochondria-Mediated
      Apoptosis Pathway in the Differentiation of Adipose-Derived Stromal Cells into
      Neurons.
AB  - Our objective is to study the relationship between the regulatory proteins Bcl
      2/Bax and mitochondria-mediated apoptosis during the differentiation of adipose
      derived stromal cells (ADSCs) into neurons. Immunocytochemistry and western
      blotting showed that the cells weakly expressed neuron-specific enolase (NSE) in
      the non-induced group and expressed NSE more strongly in the groups induced for 1
      h, 3 h, 5 h and 8 h. NSE expression peaked at 5 h (P < 0.05), although there was
      no significant difference between 5 and 8 h (P > 0.05). Bcl-2 expression
      gradually decreased over time in the non-induced group (P < 0.05). However, Bax,
      caspase-9, Cyt-c and caspase-3 expression gradually increased and peaked at 8 h
      (P < 0.05). Transmission electron microscopy revealed karyopyknosis, chromatin
      edge setting, mitochondria swelling and cavitation in cells at 5 h, and the
      mitochondrial membrane potential decreased over time, as demonstrated by laser
      scanning confocal microscopy. After a 5 h induction, cells differentiated into
      typical neurons and expressed Bcl-2, which inhibited apoptosis. Bax showed a
      strong apoptosis-promoting capacity, leading to changes in the mitochondrial
      membrane potential and structure, and then triggered the caspase-independent
      apoptotic response through the mitochondrial pathway. At the same time, Cyt-c was
      directly or indirectly released from the mitochondria to the cytoplasm to trigger
      the caspase-dependent apoptotic response through the mitochondrial pathway.
      Therefore, Bcl-2/Bax play an important role in regulating caspase-dependent and
      caspase-independent apoptosis mediated by the mitochondrial pathway during the
      differentiation of ADSCs into neurons.

PMID- 27706182
TI  - A Citizen Science Approach: A Detailed Ecological Assessment of Subtropical Reefs
      at Point Lookout, Australia.
AB  - Subtropical reefs provide an important habitat for flora and fauna, and proper
      monitoring is required for conservation. Monitoring these exposed and submerged
      reefs is challenging and available resources are limited. Citizen science is
      increasing in momentum, as an applied research tool and in the variety of
      monitoring approaches adopted. This paper aims to demonstrate an ecological
      assessment and mapping approach that incorporates both top-down (volunteer marine
      scientists) and bottom-up (divers/community) engagement aspects of citizen
      science, applied at a subtropical reef at Point Lookout, Southeast Queensland,
      Australia. Marine scientists trained fifty citizen scientists in survey
      techniques that included mapping of habitat features, recording of substrate,
      fish and invertebrate composition, and quantifying impacts (e.g., occurrence of
      substrate damage, presence of litter). In 2014 these volunteers conducted four
      seasonal surveys along semi-permanent transects, at five sites, across three
      reefs. The project presented is a model on how citizen science can be conducted
      in a marine environment through collaboration of volunteer researchers, non
      researchers and local marine authorities. Significant differences in coral and
      algal cover were observed among the three sites, while fluctuations in algal
      cover were also observed seasonally. Differences in fish assemblages were
      apparent among sites and seasons, with subtropical fish groups observed more
      commonly in colder seasons. The least physical damage occurred in the most
      exposed sites (Flat Rock) within the highly protected marine park zones. The
      broad range of data collected through this top-down/bottom-up approach to citizen
      science exemplifies the projects' value and application for identifying ecosystem
      trends or patterns. The results of the project support natural resource and
      marine park management, providing a valuable contribution to existing scientific
      knowledge and the conservation of local reefs.

PMID- 27706184
TI  - A Novel Self-Assembling DNA Nano Chip for Rapid Detection of Human Papillomavirus
      Genes.
AB  - Rapid detection of tumor-associated DNA such as Human Papillomavirus (HPV) has
      important clinical value for the early screening of tumors. By attaching
      oligonucleotides or cDNA onto the chip surface, DNA chip technology provides a
      rapid method to analyze gene expression. However, challenges remain regarding
      increasing probe density and improving detection time. To address these
      challenges, we proposed a DNA chip that was self-assembled from single stranded
      DNA in combination with high probe density and a rapid detection method. Over 200
      probes could be attached to the surface of this 100-nm diameter DNA chip. For
      detection, the chips were adsorbed onto a mica surface and then incubated for ten
      minutes with HPV-DNA; the results were directly observable using atomic force
      microscopy (AFM). This bottom-up fabricated DNA nano chip combined with high
      probe density and direct AFM detection at the single molecule level will likely
      have numerous potential clinical applications for gene screening and the early
      diagnosis of cancer.

PMID- 27706183
TI  - The Impact of Hospital/Surgeon Volume on Acute Renal Failure and Mortality in
      Liver Transplantation: A Nationwide Cohort Study.
AB  - The aim of this study was to assess whether the case volume of surgeons and
      hospitals affects the rates of postoperative complications and survival after
      liver transplantation. This population-based retrospective cohort study included
      2938 recipients of liver transplantation performed between 1998 and 2012,
      enrolled from the Taiwan National Health Insurance Research Database. They were
      divided into two groups, according to the cumulative case volume of their
      operating surgeons and the case volume of their hospitals. The duration of
      intensive care unit stay and post-transplantation hospitalization, postoperative
      complications, and mortality were analyzed. The results showed that, in the low
      and high case volume surgeons groups, respectively, acute renal failure occurred
      at the rate of 14.11% and 5.86% (p<0.0001), and the overall mortality rates were
      19.61% and 12.44% (p<0.0001). In the low and high case volume hospital groups,
      respectively, acute renal failure occurred in 11% and 7.11% of the recipients (p
      = 0.0004), and the overall mortality was 18.44% and 12.86% (p<0.0001). These
      findings suggest that liver transplantation recipients operated on higher case
      volume surgeons or in higher case volume hospitals have a lower rate of acute
      renal failure and mortality.

PMID- 27706185
TI  - Modelling Creativity: Identifying Key Components through a Corpus-Based Approach.
AB  - Creativity is a complex, multi-faceted concept encompassing a variety of related
      aspects, abilities, properties and behaviours. If we wish to study creativity
      scientifically, then a tractable and well-articulated model of creativity is
      required. Such a model would be of great value to researchers investigating the
      nature of creativity and in particular, those concerned with the evaluation of
      creative practice. This paper describes a unique approach to developing a
      suitable model of how creative behaviour emerges that is based on the words
      people use to describe the concept. Using techniques from the field of
      statistical natural language processing, we identify a collection of fourteen key
      components of creativity through an analysis of a corpus of academic papers on
      the topic. Words are identified which appear significantly often in connection
      with discussions of the concept. Using a measure of lexical similarity to help
      cluster these words, a number of distinct themes emerge, which collectively
      contribute to a comprehensive and multi-perspective model of creativity. The
      components provide an ontology of creativity: a set of building blocks which can
      be used to model creative practice in a variety of domains. The components have
      been employed in two case studies to evaluate the creativity of computational
      systems and have proven useful in articulating achievements of this work and
      directions for further research.

PMID- 27706186
TI  - Drivers of Bird Species Richness within Moist High-Altitude Grasslands in Eastern
      South Africa.
AB  - Moist high-altitude grasslands in South Africa are renowned for high avifaunal
      diversity and are priority areas for conservation. Conservation management of
      these areas conflicts with management for other uses, such as intensive livestock
      agriculture, which requires annual burning and leads to heavy grazing. Recently
      the area has become target for water storage schemes and renewable electricity
      energy projects. There is therefore an urgent need to investigate environmental
      factors and habitat factors that affect bird species richness in order to
      optimise management of those areas set aside for conservation. A particularly
      good opportunity to study these issues arose at Ingula in the eastern South
      African high-altitude grasslands. An area that had been subject to intense
      grazing was bought by the national power utility that constructed a pumped
      storage scheme on part of the land and set aside the rest for bird conservation.
      Since the new management took over in 2005 the area has been mostly annually
      burned with relatively little grazing. The new management seeks scientific advice
      on how to maintain avian species richness of the study area. We collected bird
      occurrence and vegetation data along random transects between 2006 and 2010 to
      monitor the impact of the new management, and to study the effect of the habitat
      changes on bird species richness. To achieve these, we convert bird transect data
      to presence only data to investigate how bird species richness were related to
      key transect vegetation attributes under this new grassland management. First we
      used generalised linear mixed models, to examine changes in vegetation grass
      height and cover and between burned and unburned habitats. Secondly, we examined
      how total bird species richness varied across seasons and years. And finally we
      investigated which habitat vegetation attributes were correlated with species
      richness of a group of grassland depended bird species only. Transects that were
      burned showed a larger decrease in vegetation cover compared to transects that
      were not burned. Grass height increased over time. Bird species richness was
      highest in summer compared to other seasons and increased over time. Overall bird
      species richness increased over the three summer surveys but species richness of
      birds that prefer heavily grazed habitat showed little change over the three
      years. Changes in bird species richness were best explained by the model with
      grass height for combined species richness of grassland depended birds but also
      for birds that prefer heavy grazing when treated alone. On one hand birds that
      prefer moderate grazing were best explained by a null model. However, overall
      bird species richness was better positively correlated to grass height than grass
      cover or dead grass. We conclude that frequent burning alone with relatively
      reduced grazing led to higher but less dense grass, which benefited some species
      and disadvantaged others. We suggest that management of this grassland use
      combination of fire and grazing and leave some areas unburned to accommodates
      birds of various habitat needs.

PMID- 27706187
TI  - A Molecular Approach to the Sexing of the Triple Burial at the Upper Paleolithic
      Site of Dolni Vestonice.
AB  - In the past decades ancient DNA research has brought numerous insights to
      archaeological research where traditional approaches were limited. The
      determination of sex in human skeletal remains is often challenging for physical
      anthropologists when dealing with incomplete, juvenile or pathological specimens.
      Molecular approaches allow sexing on the basis of sex-specific markers or by
      calculating the ratio of DNA derived from different chromosomes. Here we propose
      a novel approach that relies on the ratio of X chromosome-derived shotgun
      sequencing data to the autosomal coverage, thus establishing the probability of
      an XX or XY karyotype. Applying this approach to the individuals of the Upper
      Paleolithic triple burial of Dolni Vestonice reveals that all three skeletons,
      including the individual DV 15, whose sex has long been debated due to a
      pathological condition, were male.

PMID- 27706189
TI  - LudusScope: Accessible Interactive Smartphone Microscopy for Life-Science
      Education.
AB  - For centuries, observational microscopy has greatly facilitated biology
      education, but we still cannot easily and playfully interact with the microscopic
      world we see. We therefore developed the LudusScope, an accessible, interactive
      do-it-yourself smartphone microscopy platform that promotes exploratory
      stimulation and observation of microscopic organisms, in a design that combines
      the educational modalities of build, play, and inquire. The LudusScope's
      touchscreen and joystick allow the selection and stimulation of phototactic
      microorganisms such as Euglena gracilis with light. Organismal behavior is
      tracked and displayed in real time, enabling open and structured game play as
      well as scientific inquiry via quantitative experimentation. Furthermore, we used
      the Scratch programming language to incorporate biophysical modeling. This
      platform is designed as an accessible, low-cost educational kit for easy
      construction and expansion. User testing with both teachers and students
      demonstrates the educational potential of the LudusScope, and we anticipate
      additional synergy with the maker movement. Transforming observational microscopy
      into an interactive experience will make microbiology more tangible to society,
      and effectively support the interdisciplinary learning required by the Next
      Generation Science Standards.

PMID- 27706188
TI  - Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley
      Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.
AB  - In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C
      was carried out by: (1) studying horizontal gene transfer (HGT) in Sprague Dawley
      rats fed transgenic rice for 90 d; (2) examining the effect of Cry1C protein in
      vitro on digestibility and allergenicity; and (3) studying the changes of
      intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and
      subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either
      60% GM Bacillus thuringiensis (Bt) rice T1C-1 expressing Cry1C protein, the
      parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed
      no evidence of HGT between rats and transgenic rice. Sequence searching of the
      Cry1C protein showed no homology with known allergens or toxins. Cry1C protein
      was rapidly degraded in vitro with simulated gastric and intestinal fluids. The
      expressed Cry1C protein did not induce high levels of specific IgG and IgE
      antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed
      in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles
      revealed significant individual differences in the rats' intestinal microbiota.

PMID- 27706191
TI  - Two New Cynodonts (Therapsida) from the Middle-Early Late Triassic of Brazil and
      Comments on South American Probainognathians.
AB  - We describe two new cynodonts from the early Late Triassic of southern Brazil.
      One taxon, Bonacynodon schultzi gen. et sp. nov., comes from the lower Carnian
      Dinodontosaurus AZ, being correlated with the faunal association at the upper
      half of the lower member of the Chanares Formation (Ischigualasto-Villa Union
      Basin, Argentina). Phylogenetically, Bonacynodon is a closer relative to
      Probainognathus jenseni than to any other probainognathian, bearing conspicuous
      canines with a denticulate distal margin. The other new taxon is Santacruzgnathus
      abdalai gen. et sp. nov. from the Carnian Santacruzodon AZ. Although based
      exclusively on a partial lower jaw, it represents a probainognathian close to
      Prozostrodon from the Hyperodapedon AZ and to Brasilodon, Brasilitherium and
      Botucaraitherium from the Riograndia AZ. The two new cynodonts and the
      phylogenetic hypothesis presented herein indicate the degree to which our
      knowledge on probainognathian cynodonts is incomplete and also the relevance of
      the South American fossil record for understanding their evolutionary
      significance. The taxonomic diversity and abundance of probainognathians from
      Brazil and Argentina will form the basis of deep and complex studies to address
      the evolutionary transformations of cynodonts leading to mammals.

PMID- 27706190
TI  - Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic
      Nephropathy.
AB  - Oxidative stress is implicated in the pathogenesis of diabetic nephropathy (DN)
      but outcomes of many clinical trials are controversial. To define the role of
      antioxidants in kidney protection during the development of diabetic nephropathy,
      we have generated a novel genetic antioxidant mouse model with over- or under
      expression of lipoic acid synthase gene (Lias). These models have been mated with
      Ins2Akita/+ mice, a type I diabetic mouse model. We compare the major pathologic
      changes and oxidative stress status in two new strains of the mice with controls.
      Our results show that Ins2Akita/+ mice with under-expressed Lias gene, exhibit
      higher oxidative stress and more severe DN features (albuminuria, glomerular
      basement membrane thickening and mesangial matrix expansion). In contrast,
      Ins2Akita/+ mice with highly-expressed Lias gene display lower oxidative stress
      and less DN pathologic changes. Our study demonstrates that strengthening
      endogenous antioxidant capacity could be an effective strategy for prevention and
      treatment of DN.

PMID- 27706192
TI  - Population-Area Relationship for Medieval European Cities.
AB  - Medieval European urbanization presents a line of continuity between earlier
      cities and modern European urban systems. Yet, many of the spatial, political and
      economic features of medieval European cities were particular to the Middle Ages,
      and subsequently changed over the Early Modern Period and Industrial Revolution.
      There is a long tradition of demographic studies estimating the population sizes
      of medieval European cities, and comparative analyses of these data have shed
      much light on the long-term evolution of urban systems. However, the next step-to
      systematically relate the population size of these cities to their spatial and
      socioeconomic characteristics-has seldom been taken. This raises a series of
      interesting questions, as both modern and ancient cities have been observed to
      obey area-population relationships predicted by settlement scaling theory. To
      address these questions, we analyze a new dataset for the settled area and
      population of 173 European cities from the early fourteenth century to determine
      the relationship between population and settled area. To interpret this data, we
      develop two related models that lead to differing predictions regarding the
      quantitative form of the population-area relationship, depending on the level of
      social mixing present in these cities. Our empirical estimates of model
      parameters show a strong densification of cities with city population size,
      consistent with patterns in contemporary cities. Although social life in medieval
      Europe was orchestrated by hierarchical institutions (e.g., guilds, church,
      municipal organizations), our results show no statistically significant influence
      of these institutions on agglomeration effects. The similarities between the
      empirical patterns of settlement relating area to population observed here
      support the hypothesis that cities throughout history share common principles of
      organization that self-consistently relate their socioeconomic networks to
      structured urban spaces.

PMID- 27706193
TI  - Outstanding Symptoms of Poststroke Depression during the Acute Phase of Stroke.
AB  - Poststroke depression (PSD) is a critical complication which might lead to
      unfavorable outcomes. However, most cases of PSD in the acute phase, during the 2
      or 3 weeks following a stroke, are neglected because of the variable comorbid
      conditions. In this study, aimed at revealing the outstanding symptoms of PSD
      during the acute phase, consecutive patients with intracranial hemorrhage (ICH)
      or brain infarction (BI) were asked to fill out a depression questionnaire (Quick
      Inventory of Depressive Symptomatology Self-Report: QIDS-SR) at 1 week and 1
      month following stroke onset. Patients with disturbed consciousness or aphasia
      were excluded from this study. Forty-nine ICH patients and 222 BI patients
      completed the QIDS-SR at 1 week and 27 of ICH and 62 of BI at 1 month. The PSD
      rate was 67% and 46% at 1 week in ICH and BI, respectively. Although sleep
      disturbance was the most frequent symptom of PSD, psychomotor agitation and
      appetite disturbance were the most distinguishing symptoms in ICH at 1 week and
      fatigue at 1 month. On the other hand, most of the depressive symptoms addressed
      in QIDS-SR were observed in PSD of BI patients both at 1 week and 1 month. In
      conclusion, while sleep disturbance was a frequent but non-specific symptom,
      appetite disturbance and fatigue might be critical symptoms to suggest PSD during
      the acute phase of stroke.

PMID- 27706194
TI  - Work-Related Factors Considered by Sickness-Absent Employees When Estimating
      Timeframes for Returning to Work.
AB  - INTRODUCTION: Work-related factors have been found to be influential in shaping a
      number of return-to-work outcomes including return-to-work expectations. Based on
      the idea that work-related factors have the potential for modification through
      workplace-based initiatives, this study involved a detailed examination of work
      related factors referenced by workers as being taken into consideration when
      estimating timeframes for returning to work. METHODS: Focus groups were conducted
      with 30 employees, currently off work (<= 3 months) due to a musculoskeletal
      condition. During the focus groups, participants wrote and spoke about the
      factors that they considered when forming their expectations for returning to
      work. Data were subjected to thematic content analysis. RESULTS: Discussions
      revealed that participants' considerations tended to differ depending on whether
      or not they had a job to return to. Those with jobs (n = 23) referenced specific
      influences such as working relationships, accommodations, physical and practical
      limitations, as well as concerns about their ability to do their job. Those
      without a job to return to (n = 7) talked about the ways they would go about
      finding work, and how long they thought this would take. Both groups mentioned
      the influence of wanting to find the "right" job, retraining and being limited
      due to the need for income. CONCLUSION: Findings indicate that employees
      reference numerous work-related factors when estimating their timeframes for
      returning to work, and that many of these have been previously identified as
      relating to other return-to-work outcomes. Findings suggest the potential to
      improve return-to-work expectation through addressing work-related influences,
      and helping people work through the tasks they need to complete in order to move
      forward in the return-to-work process.

PMID- 27706195
TI  - A Possible Link between Gastric Mucosal Atrophy and Gastric Cancer after
      Helicobacter pylori Eradication.
AB  - BACKGROUND: The effect of H. pylori eradication in gastric cancer prevention can
      be attributed to the improvement of atrophic gastritis, which is a known risk of
      gastric cancer. However, gastric cancer has also been diagnosed after long-term
      H. pylori eradication. This study aimed to clarify the association between
      gastric atrophy and gastric cancer after H. pylori eradication, including its
      clinicopathological features. METHODS: A total of 55 consecutive patients with 64
      early gastric cancers (EGCs) diagnosed after H. pylori eradication were enrolled.
      The degree of endoscopic atrophy and the histological degrees of mononuclear cell
      infiltration, atrophy, and metaplasia in the corpus and adjacent mucosa of the
      EGCs were determined and scored. RESULTS: The majority of EGCs (63/64) were
      located within the endoscopically assessed atrophic mucosa or along the atrophic
      border. The adjacent mucosa of the EGCs presented significantly higher degrees of
      all histological parameters than in the corpus (mononuclear cell infiltration,
      0.86+/-0.09 vs. 0.51+/-0.11, P = 0.016; atrophy, 1.77+/-0.13 vs. 0.65+/-0.14,
      P<0.0001; metaplasia, 1.68+/-0.13 vs. 0.48+/-0.1, P<0.0001). The degree of
      endoscopic atrophy improved in the patients with longer post-H. pylori
      eradication periods; however, this trend was not observed for the histological
      parameters, and high degrees of atrophy and metaplasia were observed in the
      adjacent mucosa of the EGCs compared with the corpus during all periods (all
      P<0.05). The histological degrees of atrophy and metaplasia in the adjacent
      mucosa were particularly higher in the patients who underwent eradication due to
      gastric ulcers. CONCLUSIONS: Severe gastric atrophy remained in the adjacent
      mucosa of the EGCs after H. pylori eradication, which may be linked to gastric
      carcinogenesis.

PMID- 27706197
TI  - Communally Nesting Migratory Birds Create Ecological Hot-Spots in Tropical
      Australia.
AB  - Large numbers of metallic starlings (Aplonis metallica) migrate annually from New
      Guinea to the rainforests of tropical Australia, where they nest communally in
      single emergent trees (up to 1,000 birds). These aggregations create dense and
      species-rich faunal "hot-spots", attracting a diverse assemblage of local
      consumers that utilise this seasonal resource. The starlings nested primarily in
      poison-dart trees (Antiaris toxicaria) near the rainforest-woodland boundary.
      Surveys underneath these colonies revealed that bird-derived nutrients massively
      increased densities of soil invertebrates and mammals (primarily wild pigs)
      beneath trees, year-round. Flying invertebrates, nocturnal birds, reptiles, and
      amphibians congregated beneath the trees when starlings were nesting (the wet
      season). Diurnal birds (primarily cockatoos and bush turkeys) aggregated beneath
      the trees during the dry-season to utilise residual nutrients when the starlings
      were not nesting. The abundance of several taxa was considerably higher (to >
      1000-fold) under colony trees than under nearby trees. The system strikingly
      resembles utilisation of bird nesting colonies by predators in other parts of the
      world but this spectacular system has never been described, emphasizing the
      continuing need for detailed natural-history studies in tropical Australia.

PMID- 27706196
TI  - Reliability of a Novel High Intensity One Leg Dynamic Exercise Protocol to
      Measure Muscle Endurance.
AB  - We recently developed a high intensity one leg dynamic exercise (OLDE) protocol
      to measure muscle endurance and investigate the central and peripheral mechanisms
      of muscle fatigue. The aims of the present study were to establish the
      reliability of this novel protocol and describe the isokinetic muscle fatigue
      induced by high intensity OLDE and its recovery. Eight subjects performed the
      OLDE protocol (time to exhaustion test of the right leg at 85% of peak power
      output) three times over a week period. Isokinetic maximal voluntary contraction
      torque at 60 (MVC60), 100 (MVC100) and 140 (MVC140) deg/s was measured pre
      exercise, shortly after exhaustion (13 +/- 4 s), 20 s (P20) and 40 s (P40) post
      exercise. Electromyographic (EMG) signal was analyzed via the root mean square
      (RMS) for all three superficial knee extensors. Mean time to exhaustion was 5.96
      +/- 1.40 min, coefficient of variation was 8.42 +/- 6.24%, typical error of
      measurement was 0.30 min and intraclass correlation was 0.795. MVC torque
      decreased shortly after exhaustion for all angular velocities (all P < 0.001).
      MVC60 and MVC100 recovered between P20 (P < 0.05) and exhaustion and then
      plateaued. MVC140 recovered only at P40 (P < 0.05). High intensity OLDE did not
      alter maximal EMG RMS of the three superficial knee extensors during MVC. The
      results of this study demonstrate that this novel high intensity OLDE protocol
      could be reliably used to measure muscle endurance, and that muscle fatigue
      induced by high intensity OLDE should be examined within ~ 30 s following
      exhaustion.

PMID- 27706198
TI  - The Asian Correction Can Be Quantitatively Forecasted Using a Statistical Model
      of Fusion-Fission Processes.
AB  - The Global Financial Crisis of 2007-2008 wiped out US$37 trillions across global
      financial markets, this value is equivalent to the combined GDPs of the United
      States and the European Union in 2014. The defining moment of this crisis was the
      failure of Lehman Brothers, which precipitated the October 2008 crash and the
      Asian Correction (March 2009). Had the Federal Reserve seen these crashes coming,
      they might have bailed out Lehman Brothers, and prevented the crashes altogether.
      In this paper, we show that some of these market crashes (like the Asian
      Correction) can be predicted, if we assume that a large number of adaptive
      traders employing competing trading strategies. As the number of adherents for
      some strategies grow, others decline in the constantly changing strategy space.
      When a strategy group grows into a giant component, trader actions become
      increasingly correlated and this is reflected in the stock price. The
      fragmentation of this giant component will leads to a market crash. In this
      paper, we also derived the mean-field market crash forecast equation based on a
      model of fusions and fissions in the trading strategy space. By fitting the
      continuous returns of 20 stocks traded in Singapore Exchange to the market crash
      forecast equation, we obtain crash predictions ranging from end October 2008 to
      mid-February 2009, with early warning four to six months prior to the crashes.

PMID- 27706199
TI  - An Outcome-Weighted Network Model for Characterizing Collaboration.
AB  - Shared patient encounters form the basis of collaborative relationships, which
      are crucial to the success of complex and interdisciplinary teamwork in
      healthcare. Quantifying the strength of these relationships using shared risk
      adjusted patient outcomes provides insight into interactions that occur between
      healthcare providers. We developed the Shared Positive Outcome Ratio (SPOR), a
      novel parameter that quantifies the concentration of positive outcomes between a
      pair of healthcare providers over a set of shared patient encounters. We
      constructed a collaboration network using hospital emergency department patient
      data from electronic health records (EHRs) over a three-year period. Based on an
      outcome indicating patient satisfaction, we used this network to assess pairwise
      collaboration and evaluate the SPOR. By comparing this network of 574 providers
      and 5,615 relationships to a set of networks based on randomized outcomes, we
      identified 295 (5.2%) pairwise collaborations having significantly higher patient
      satisfaction rates. Our results show extreme high- and low-scoring relationships
      over a set of shared patient encounters and quantify high variability in
      collaboration between providers. We identified 29 top performers in terms of
      patient satisfaction. Providers in the high-scoring group had both a greater
      average number of associated encounters and a higher percentage of total
      encounters with positive outcomes than those in the low-scoring group, implying
      that more experienced individuals may be able to collaborate more successfully.
      Our study shows that a healthcare collaboration network can be structurally
      evaluated to characterize the collaborative interactions that occur between
      healthcare providers in a hospital setting.

PMID- 27706200
TI  - Early Warning Signals of Social Transformation: A Case Study from the US
      Southwest.
AB  - Recent research in ecology suggests that generic indicators, referred to as early
      warning signals (EWS), may occur before significant transformations, both
      critical and non-critical, in complex systems. Up to this point, research on EWS
      has largely focused on simple models and controlled experiments in ecology and
      climate science. When humans are considered in these arenas they are invariably
      seen as external sources of disturbance or management. In this article we explore
      ways to include societal components of socio-ecological systems directly in EWS
      analysis. Given the growing archaeological literature on 'collapses,' or
      transformations, in social systems, we investigate whether any early warning
      signals are apparent in the archaeological records of the build-up to two
      contemporaneous cases of social transformation in the prehistoric US Southwest,
      Mesa Verde and Zuni. The social transformations in these two cases differ in
      scope and severity, thus allowing us to explore the contexts under which warning
      signals may (or may not) emerge. In both cases our results show increasing
      variance in settlement size before the transformation, but increasing variance in
      social institutions only before the critical transformation in Mesa Verde. In the
      Zuni case, social institutions appear to have managed the process of significant
      social change. We conclude that variance is of broad relevance in anticipating
      social change, and the capacity of social institutions to mitigate transformation
      is critical to consider in EWS research on socio-ecological systems.

PMID- 27706201
TI  - Cell Blebbing in Confined Microfluidic Environments.
AB  - Migrating cells can extend their leading edge by forming myosin-driven blebs and
      F-actin-driven pseudopods. When coerced to migrate in resistive environments,
      Dictyostelium cells switch from using predominately pseudopods to blebs. Bleb
      formation has been shown to be chemotactic and can be influenced by the direction
      of the chemotactic gradient. In this study, we determine the blebbing responses
      of developed cells of Dictyostelium discoideum to cAMP gradients of varying
      steepness produced in microfluidic channels with different confining heights,
      ranging between 1.7 MUm and 3.8 MUm. We show that microfluidic confinement
      height, gradient steepness, buffer osmolarity and Myosin II activity are
      important factors in determining whether cells migrate with blebs or with
      pseudopods. Dictyostelium cells were observed migrating within the confines of
      microfluidic gradient channels. When the cAMP gradient steepness is increased
      from 0.7 nM/MUm to 20 nM/MUm, cells switch from moving with a mixture of blebs
      and pseudopods to moving only using blebs when chemotaxing in channels with
      confinement heights less than 2.4 MUm. Furthermore, the size of the blebs
      increases with gradient steepness and correlates with increases in myosin-II
      localization at the cell cortex. Reduction of intracellular pressure by high
      osmolarity buffer or inhibition of myosin-II by blebbistatin leads to a decrease
      in bleb formation and bleb size. Together, our data reveal that the protrusion
      type formed by migrating cells can be influenced by the channel height and the
      steepness of the cAMP gradient, and suggests that a combination of confinement
      induced myosin-II localization and cAMP-regulated cortical contraction leads to
      increased intracellular fluid pressure and bleb formation.

PMID- 27706202
TI  - PubMedPortable: A Framework for Supporting the Development of Text Mining
      Applications.
AB  - Information extraction from biomedical literature is continuously growing in
      scope and importance. Many tools exist that perform named entity recognition,
      e.g. of proteins, chemical compounds, and diseases. Furthermore, several
      approaches deal with the extraction of relations between identified entities. The
      BioCreative community supports these developments with yearly open challenges,
      which led to a standardised XML text annotation format called BioC. PubMed
      provides access to the largest open biomedical literature repository, but there
      is no unified way of connecting its data to natural language processing tools.
      Therefore, an appropriate data environment is needed as a basis to combine
      different software solutions and to develop customised text mining applications.
      PubMedPortable builds a relational database and a full text index on PubMed
      citations. It can be applied either to the complete PubMed data set or an
      arbitrary subset of downloaded PubMed XML files. The software provides the
      infrastructure to combine stand-alone applications by exporting different data
      formats, e.g. BioC. The presented workflows show how to use PubMedPortable to
      retrieve, store, and analyse a disease-specific data set. The provided use cases
      are well documented in the PubMedPortable wiki. The open-source software library
      is small, easy to use, and scalable to the user's system requirements. It is
      freely available for Linux on the web at
      https://github.com/KerstenDoering/PubMedPortable and for other operating systems
      as a virtual container. The approach was tested extensively and applied
      successfully in several projects.

PMID- 27706203
TI  - Longitudinal Lung Function Decrease in Subjects with Spontaneous Healed Pulmonary
      Tuberculosis.
AB  - OBJECTIVE: We compared the longitudinal course of post-bronchodilator Forced
      Expiratory Volume in 1 second (pFEV1) over a 10-year period in subjects with
      spontaneous healed pulmonary tuberculosis (SHPTB) with that in normal subjects.
      METHODS: We prospectively investigated 339 subjects with SHPTB and 3211 normal
      subjects. pFEV1 values measured biannually over 10 years were analyzed using
      mixed effects model. RESULTS: At baseline, there were no differences in gender,
      smoking amount, and mean height, except mean age (50.0 +/- 8.1 VS. 48.1 +/- 7.3,
      P< 0.001) between the SHPTB and normal group. 52% of the 339 participants with
      SHPTB and 56% of the 3211 normal participants participated till the end of study.
      According to the final model, the SHPTB group showed significantly larger
      decrease in the average pFEV1 over the time than the normal group (P< 0.001)
      adjusted for gender, age, height, smoking pack years, and time effects.
      Especially, the interaction effect between time and group was statistically
      significant (P = 0.036). CONCLUSION: The average lung function in terms of pFEV1
      decreases faster in subjects with SHPTB than in normal individuals over time.

PMID- 27706204
TI  - Neuronal NTPDase3 Mediates Extracellular ATP Degradation in Trigeminal
      Nociceptive Pathway.
AB  - ATP induces pain via activation of purinergic receptors in nociceptive sensory
      nerves. ATP signaling is terminated by ATP hydrolysis mediated by cell surface
      localized ecto-nucleotidases. Using enzymatic histochemical staining, we show
      that ecto-ATPase activity is present in mouse trigeminal nerves. Using
      immunofluorescence staining, we found that ecto-NTPDase3 is expressed in
      trigeminal nociceptive neurons and their projections to the brainstem. In
      addition, ecto-ATPase activity and ecto-NTPDase3 are also detected in the
      nociceptive outermost layer of the trigeminal subnucleus caudalis. Furthermore,
      we demonstrate that incubation with anti-NTPDase3 serum reduces extracellular ATP
      degradation in the nociceptive lamina of both the trigeminal subnucleus caudalis
      and the spinal cord dorsal horn. These results are consistent with neuronal
      NTPDase3 activity modulating pain signal transduction and transmission by
      affecting extracellular ATP hydrolysis within the trigeminal nociceptive pathway.
      Thus, disruption of trigeminal neuronal NTPDase3 expression and localization to
      presynaptic terminals during chronic inflammation, local constriction and injury
      may contribute to the pathogenesis of orofacial neuropathic pain.

PMID- 27706205
TI  - Action of SNAIL1 in Cardiac Myofibroblasts Is Important for Cardiac Fibrosis
      following Hypoxic Injury.
AB  - Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac
      dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor
      implicated in fibrosis following organ injury and cancer. To determine if the
      action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we
      used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout
      mouse models. Here we report that SNAIL1 expression is upregulated in the
      infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac
      fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I
      increase SNAIL1 protein level. SNAIL1 is required in cardiac fibroblasts for the
      adoption of myofibroblast fate, collagen I expression and expression of fibrosis
      related genes. Taken together this data suggests that SNAIL1 expression is
      induced in the cardiac fibroblasts after hypoxic injury and contributes to
      myofibroblast phenotype and a fibrotic scar formation. Resultant collagen
      deposition in the scar can maintain elevated SNAIL1 expression in the
      myofibroblasts and help propagate fibrosis.

PMID- 27706206
TI  - Incidences and Risk Factors of Organ Manifestations in the Early Course of
      Systemic Sclerosis: A Longitudinal EUSTAR Study.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is a rare and clinically heterogeneous
      autoimmune disorder characterised by fibrosis and microvascular obliteration of
      the skin and internal organs. Organ involvement mostly manifests after a variable
      period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence
      and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement
      in the early course of SSc. METHODS: In the EUSTAR cohort, patients with early
      SSc were identified as those who had a visit within the first year after RP
      onset. Incident SSc organ manifestations and their risk factors were assessed
      using Kaplan-Meier methods and Cox regression analysis. RESULTS: Of the 695 SSc
      patients who had a baseline visit within 1 year after RP onset, the incident non
      RP manifestations (in order of frequency) were: skin sclerosis (75%) GI symptoms
      (71%), impaired diffusing capacity for monoxide<80% predicted (65%), DU (34%),
      cardiac involvement (32%), FVC<80% predicted (31%), increased PAPsys>40mmHg
      (14%), and renal crisis (3%). In the heart, incidence rates were highest for
      diastolic dysfunction, followed by conduction blocks and pericardial effusion.
      While the main baseline risk factor for a short timespan to develop FVC
      impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient
      age. The main risk factors for incident cardiac manifestations were anti
      topoisomerase autoantibody positivity and older age. Male sex, anti-RNA
      polymerase-III positivity, and older age were risk factors associated with
      incident renal crisis. CONCLUSION: In SSc patients presenting early after RP
      onset, approximately half of all incident organ manifestations occur within 2
      years and have a simultaneous rather than a sequential onset. These findings have
      implications for the design of new diagnostic and therapeutic strategies aimed to
      'widen' the still very narrow 'window of opportunity'. They may also enable
      physicians to counsel and manage patients presenting early in the course of SSc
      more accurately.

PMID- 27706207
TI  - Adiponectin Fractions Influence the Development of Posttransplant Diabetes
      Mellitus and Cardiovascular Disease in Japanese Renal Transplant Recipients.
AB  - BACKGROUND: A few studies have investigated the role of adiponectin fraction for
      cardiovascular disease (CVD) in RTx recipients. SUBJECTS AND METHODS: We studied
      57 adult subjects (39 males, 18 females; 10 cadaveric donors) with at least three
      years of allograft survival (median 251 months). We examined clinical backgrounds
      such as treated drugs, blood pressure (BP, mmHg), body mass index (BMI), and
      blood chemistry including cholesterol (total, LDL-C, HDL-C), glucose, glycated
      hemoglobin (HbA1c), and serum high and low-molecular-weight (HMW/LMW) ADPN
      fractions with regard to the associations of the visceral and subcutaneous fat
      areas on CT scan. We also analyzed the associations of CVD and post-transplant
      diabetes (PTDM) with ADPN fractions and the fat areas. RESULTS: The visceral fat
      area was inversely correlated with serum HMW and LMW ADPN levels and HMW ADPN
      ratio (r = -0.400, p = 0.002 and r = -0.296, p = 0.025 and r = -0.444, p<0.001,
      respectively). Furthermore, the visceral fat area was positively with the LMW
      ADPN ratio (r = 0.467, p<0.001), but no significant correlation was noted between
      the subcutaneous fat area and the ADPN ratio. On multiple regression analysis,
      eGFR and the visceral fat area were significant reducing factors of HMW ADPN
      levels, and the alteration of eGFR was identified as an increasing factor of HMW
      ADPN levels. Patients with CVD had larger visceral fat area (p = 0.004), lower
      HMW ADPN ratio (p = 0.022) and higher LMW ADPN ratio (p = 0.049). In addition,
      the higher HMW ADPN ratio and statin treatment were identified as reducing
      factors of the development of CVD, but the LDL-C level was an aggravating factor.
      Moreover, the higher LMW ADPN ratio and the visceral fat area were aggravating
      factors of PTDM. CONCLUSION: Even in Japanese renal transplant recipients,
      visceral fat area and ADPN fractions were significant factors for the development
      of both CVD and PTDM.

PMID- 27706208
TI  - Influence of the Infrapatellar Fat Pad Resection during Total Knee Arthroplasty:
      A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: To enhance surgical exposure, resection of the infrapatellar fat pad
      (IPFP) is usually a routine procedure in total knee arthroplasty (TKA). However,
      there is conflicting evidence regarding whether IPFP resection during TKA impairs
      clinical outcome. We performed a systematic review and meta-analysis to clarify
      the influence of IPFP resection on primary TKA. METHODS: Embase, PubMed, and the
      Cochrane Library were systematically searched up to August 2016 to identify
      relevant studies. All clinical studies comparing IPFP resection (IPFP-R) and IPFP
      preservation (IPFP-P) in patients undergoing primary TKA were obtained. The meta
      analysis was performed with Revman 5.3 and STATA 12.0 software. The weighted mean
      was estimated by using random effects (RE) models with 95% CIs, heterogeneity was
      assessed using the H statistic and the inconsistency index (I2). RESULTS: Seven
      studies involving 2,734 patients (3,258 knees) were included. IPFP resection
      trended to increase the incidence of postoperative anterior knee pain within 2
      months postoperatively, compared with patients in whom the IPFP was preserved
      (odds ratio [OR]s 2.12[0.95, 4.73], p = 0.07). An increased incidence of anterior
      knee pain was observed in the IPFP resection group > 12 months postoperatively,
      but the difference was not significant (OR, 3.69 [0.81, 16.82], p = 0.07). In
      addition, a trend towards more shortening of the patellar tendon was also
      observed in the IPFP-R group. No significant results were found regarding
      postoperative knee function. CONCLUSION: These results suggest that preserving
      the IPFP may be superior to IPFP resection in patients undergoing primary TKA,
      due to the relatively lower rate of anterior knee pain after short-term follow
      up.

PMID- 27706209
TI  - Adipose-Derived Stem Cells Respond to Increased Osmolarities.
AB  - Cell therapies present a feasible option for the treatment of degenerated
      cartilaginous and intervertebral disc (IVD) tissues. Microenvironments of these
      tissues are specific and often differ from the microenvironment of cells that,
      could be potentially used for therapy, e.g. human adipose-derived stem cells
      (hASC). To ensure safe and efficient implantation of hASC, it is important to
      evaluate how microenvironmental conditions at the site of implantation affect the
      implanted cells. This study has demonstrated that cartilaginous tissue-specific
      osmolarities ranging from 400-600 mOsm/L affected hASC in a dose- and time
      dependent fashion in comparison to 300 mOsm/L. Increased osmolarities resulted in
      transient (nuclear DNA and actin reorganisation) and non-transient, long-term
      morphological changes (vesicle formation, increase in cell area, and culture
      morphology), as well as reduced proliferation in monolayer cultures. Increased
      osmolarities diminished acid proteoglycan production and compactness of
      chondrogenically induced pellet cultures, indicating decreased chondrogenic
      potential. Viability of hASC was strongly dependent on the type of culture, with
      hASC in monolayer culture being more tolerant to increased osmolarity compared to
      hASC in suspension, alginate-agarose hydrogel, and pellet cultures, thus
      emphasizing the importance of choosing relevant in vitro conditions according to
      the specifics of clinical application.

PMID- 27706210
TI  - Molecular Typing of Legionella pneumophila Isolates in the Province of Quebec
      from 2005 to 2015.
AB  - Legionella is found in natural and man-made aquatic environments, such as cooling
      towers and hot water plumbing infrastructures. Legionella pneumophila serogroup 1
      (Lp1) is the most common etiological agent causing waterborne disease in the
      United States and Canada. This study reports the molecular characterization of Lp
      strains during a 10 year period. We conducted sequence-based typing (SBT)
      analysis on a large set of Lp isolates (n = 284) to investigate the province of
      Quebec sequence types (STs) distribution in order to identify dominant clusters.
      From 2005 to 2015, 181 clinical Lp isolates were typed by SBT (141 sporadic cases
      and 40 outbreak related cases). From the same period of time, 103 environmental
      isolates were also typed. Amongst the 108 sporadic cases of Lp1 typed, ST-62 was
      the most frequent (16.6%), followed by ST-213 (10.2%), ST-1 (8.3%) and ST-37
      (8.3%). Amongst other serogroups (SG), ST-1327 (SG5) (27.3%) and ST-378 (SG10)
      (12.2%) were the most frequent. From the environmental isolates, ST-1 represent
      the more frequent SBT type (26.5%). Unweighted pair group method with arithmetic
      mean (UPGMA) dendrogram from the 108 sporadic cases of SG1 contains 4 major
      clusters (A to D) of related STs. Cluster B contains the majority of the strains
      (n = 61) and the three most frequent STs in our database (ST-62, ST-213 and ST
      1). During the study period, we observed an important increase in the incidence
      rate in Quebec. All the community associated outbreaks, potentially or confirmed
      to be associated with a cooling tower were caused by Lp1 strains, by opposition
      to hospital associated outbreaks that were caused by serogroups of Lp other than
      SG1. The recent major Quebec City outbreak caused by ST-62, and the fact that
      this genotype is the most common in the province supports whole genome sequencing
      characterization of this particular sequence type in order to understand its
      evolution and associated virulence factors.

PMID- 27706211
TI  - Altered Immune Cytokine Expression Associated with KoRV B Infection and Season in
      Captive Koalas.
AB  - Koala (Phascolarctos cinereus) populations are increasingly vulnerable and one of
      the main threats is chlamydial infection. Koala retrovirus (KoRV) has been
      proposed as an underlying cause of the koala's susceptibility to infection with
      Chlamydia and high rates of lymphoid neoplasia; however, the regionally
      ubiquitous, endogenous nature of this virus suggests that KoRV A infection is not
      sufficient for immune suppression to occur. A recently discovered exogenous
      variant of KoRV, KoRV B, has several structural elements that cause increased
      pathogenicity in related retroviruses and was associated with lymphoid neoplasia
      in one study. The present study assesses whether KoRV B infection is associated
      with alterations in immune function. Cytokine gene expression by mitogen
      stimulated lymphocytes of KoRV B positive (n = 5-6) and negative (n = 6-7)
      captive koalas was evaluated by qPCR four times (April 2014-February 2015) to
      control for seasonal variation. Key immune genes in the Th1 pathway (IFNgamma,
      TNFalpha), Th2 pathway (IL 10, IL4, IL6) and Th17 pathway (IL17A), along with
      CD4:CD8 ratio, were assessed. KoRV B positive koalas showed significantly
      increased up-regulation of IL17A and IL10 in three out of four sampling periods
      and IFNgamma, IL6, IL4 and TNFalpha in two out of four. IL17A is an immune marker
      for chlamydial pathogenesis in the koala; increased expression of IL17A in KoRV B
      positive koalas, and concurrent immune dysregulation, may explain the differences
      in susceptibility to chlamydial infection and severity of disease seen between
      individuals and populations. There was also marked seasonal variation in up
      regulation for most of the cytokines and the CD4:CD8 ratio. The up-regulation in
      both Th1 and Th2 cytokines mirrors changes associated with immune dysregulation
      in humans and felids as a result of retroviral infections. This is the first
      report of altered immune expression in koalas infected by an exogenous variant of
      KoRV and also the first report of seasonal variation in cytokine up-regulation
      and CD4:CD8 ratio in marsupials.

PMID- 27706213
TI  - SeqKit: A Cross-Platform and Ultrafast Toolkit for FASTA/Q File Manipulation.
AB  - FASTA and FASTQ are basic and ubiquitous formats for storing nucleotide and
      protein sequences. Common manipulations of FASTA/Q file include converting,
      searching, filtering, deduplication, splitting, shuffling, and sampling. Existing
      tools only implement some of these manipulations, and not particularly
      efficiently, and some are only available for certain operating systems.
      Furthermore, the complicated installation process of required packages and
      running environments can render these programs less user friendly. This paper
      describes a cross-platform ultrafast comprehensive toolkit for FASTA/Q
      processing. SeqKit provides executable binary files for all major operating
      systems, including Windows, Linux, and Mac OSX, and can be directly used without
      any dependencies or pre-configurations. SeqKit demonstrates competitive
      performance in execution time and memory usage compared to similar tools. The
      efficiency and usability of SeqKit enable researchers to rapidly accomplish
      common FASTA/Q file manipulations. SeqKit is open source and available on Github
      at https://github.com/shenwei356/seqkit.

PMID- 27706212
TI  - The yapA Encodes bZIP Transcription Factor Involved in Stress Tolerance in
      Pathogenic Fungus Talaromyces marneffei.
AB  - Talaromyces marneffei, formerly Penicillium marneffei, is a thermally dimorphic
      fungus. It causes a fatal disseminated disease in patients infected with the
      human immunodeficiency virus (HIV). Studies on the stress defense mechanism of T.
      marneffei can lead to a better understanding of the pathogenicity and the
      progression of the disease due to this fungus. The basic leucine-zipper (bZip)
      transcription factor gene in Saccharomyces cerevisiae, named yap1 (yeast
      activating protein-1), is known as a crucial central regulator of stress
      responses including those caused by oxidative agents, cadmium, and drugs. An
      ortholog of yap1, designated yapA, was identified in T. marneffei. We found that
      the yapA gene was involved in growth and fungal cell development. The yapA
      deletion mutant exhibited delays in the rate of growth, germination, and
      conidiation. Surprisingly, the yapA gene was also involved in the pigmentation of
      T. marneffei. Moreover, the mutant was sensitive to oxidative stressors such as
      H2O2 and menadione, similar to S. cerevisiae yap1 mutant, as well as the
      nitrosative stressor NaNO2. In addition, the yapA mutant demonstrated
      significantly decreased survival in human macrophage THP-1 compared to wild-type
      and complemented strains. This study reveals the role of yapA in fungal growth,
      cell development, stress response, and potential virulence in T. marneffei.

PMID- 27706214
TI  - Regulation of the Flavonoid Biosynthesis Pathway Genes in Purple and Black Grains
      of Hordeum vulgare.
AB  - Barley grain at maturity can have yellow, purple, blue, and black pigmentations
      which are suggested to play a protective role under stress conditions. The first
      three types of the colors are caused by phenolic compounds flavonoids; the last
      one is caused by phytomelanins, oxidized and polymerized phenolic compounds.
      Although the genetic basis of the flavonoid biosynthesis pathway in barley has
      been thoroughly studied, there is no data yet on its regulation in purple and
      black barley grains. In the current study, genetic model of Hordeum vulgare
      'Bowman' near-isogenic lines (NILs) was used to investigate the regulation of the
      flavonoid biosynthesis in white, purple, and black barley grains. Microsatellite
      genotyping revealed donor segments in the purple- and black-grained lines on
      chromosomes 2H (in region of the Ant2 gene determining purple color of grains)
      and 1H (in region of the Blp gene determining black lemma and pericarp),
      respectively. The isolated dominant Ant2 allele of the purple-grained line has
      high level of sequence similarity with the recessive Bowman's ant2 in coding
      region, whereas an insertion of 179 bp was detected in promoter region of ant2.
      This structural divergence between Ant2 and ant2 alleles may underlie their
      different expression in grain pericarp: Bowman's Ant2 is not transcribed, whereas
      it was up-regulated in the purple-grained line with coordinately co-expressed
      flavonoid biosynthesis structural genes (Chs, Chi, F3h, F3'h, Dfr, Ans). This led
      to total anthocyain content increase in purple-grained line identified by ultra
      performance liquid chromatography (HPLC). Collectively, these results proved the
      regulatory function of the Ant2 gene in anthocyanin biosynthesis in barley grain
      pericarp. In the black-grained line, the specific transcriptional regulation of
      the flavonoid biosynthesis pathway genes was not detected, suggesting that
      flavonoid pigments are not involved in development of black lemma and pericarp
      trait.

PMID- 27706215
TI  - Alterations of Myelin Content in Parkinson's Disease: A Cross-Sectional
      Neuroimaging Study.
AB  - Alterations to myelin may be a core pathological feature of neurodegenerative
      diseases. Although white matter microstructural differences have been described
      in Parkinson's disease (PD), it is unknown whether such differences include
      alterations of the brain's myelin content. Thus, the objective of the current
      study is to measure and compare brain myelin content between PD patients and age
      matched controls. In this cross-sectional study, 63 participants from the
      Longitudinal MRI in Parkinson's Disease study underwent brain MRI, Unified
      Parkinson's Disease Rating Scale (UPDRS) scoring, and cognitive asessments.
      Subjects were imaged with the mcDEPSOT (multi-component driven equilibrium single
      pulse observation of T1 and T2), a multicomponent relaxometry technique that
      quantifies longitudinal and transverse relaxation rates (R1 and R2, respectively)
      and the myelin water fraction (VFM), a surrogate for myelin content. A voxel-wise
      approach was used to compare R1, R2, and VFM measures between PD and control
      groups, and to evaluate relationships with age as well as disease duration, UPDRS
      scores, and daily levodopa equivalent dose. PD subjects had higher VFM than
      controls in frontal and temporal white matter and bilateral thalamus. Greater age
      was strongly associated with lower VFM in both groups, while an age-by-group
      interaction suggested a slower rate of VFM decline in the left putamen with aging
      in PD. Within the PD group, measures of disease severity, including UPDRS, daily
      levodopa equivalent dose, and disease duration, were observed to be related with
      myelin content in diffuse brain regions. The age-by-group interaction suggests
      that either PD or dopaminergic therapies allay observed age-related myelin
      changes. The relationships between VFM and disease severity measures suggests
      that VFM may provide a surrogate marker for microstructural changes related to
      Parkinson's disease.

PMID- 27706217
TI  - Application of 2,4-Dinitrophenylhydrazine (DNPH) in High-Throughput Screening for
      Microorganism Mutants Accumulating 9alpha-Hydroxyandrost-4-ene-3,17-dione (9alpha
      OH-AD).
AB  - To develop a quick method for the preliminarily screening of mutant strains that
      can accumulate 9alpha-hydroxyandrost-4-ene-3,17-dione (9alpha-OH-AD), a high
      throughput screening method was presented by applying the principle that 2,4
      dinitrophenylhydrazine (DNPH) can react with ketones to produce precipitation.
      The optimal color assay conditions were the substrate androst-4-ene-3,17-dione
      (AD) concentration at 2.0 g/L, the ratio of AD to DNPH solution at 1:4, and the
      sulfuric acid and ethanol solution percentages in DNPH solution at 2% and 35%,
      respectively. This method was used to preliminarily screen the mutants of
      Rhodococcus rhodochrous DSM43269, from which the three ones obtained could
      produce more 9alpha-OH-AD. This DNPH color assay method not only broadens
      screening methods and increases screening efficiency in microbial mutation
      breeding but also establishes a good foundation for obtaining strains for
      industrial application.

PMID- 27706216
TI  - Clinical and Economic Impact of a Digital, Remotely-Delivered Intensive
      Behavioral Counseling Program on Medicare Beneficiaries at Risk for Diabetes and
      Cardiovascular Disease.
AB  - BACKGROUND: Type 2 diabetes and cardiovascular disease impose substantial
      clinical and economic burdens for seniors (age 65 and above) and the Medicare
      program. Intensive Behavioral Counseling (IBC) interventions like the National
      Diabetes Prevention Program (NDPP), have demonstrated effectiveness in reducing
      excess body weight and lowering or delaying morbidity onset. This paper estimated
      the potential health implications and medical savings of a digital version of IBC
      modeled after the NDPP. METHODS AND FINDINGS: Participants in this digital IBC
      intervention, the Omada program, include 1,121 overweight or obese seniors with
      additional risk factors for diabetes or heart disease. Weight changes were
      objectively measured via participant use of a networked weight scale.
      Participants averaged 6.8% reduction in body weight within 26 weeks, and 89% of
      participants completed 9 or more of the 16 core phase lessons. We used a Markov
      based microsimulation model to simulate the impact of weight loss on future
      health states and medical expenditures over 10 years. Cumulative per capita
      medical expenditure savings over 3, 5 and 10 years ranged from $1,720 to 1,770 (3
      years), $3,840 to $4,240 (5 years) and $11,550 to $14,200 (10 years). The range
      reflects assumptions of weight re-gain similar to that seen in the DPP clinical
      trial (lower bound) or minimal weight re-gain aligned with age-adjusted national
      averages (upper bound). The estimated net economic benefit after IBC costs is
      $10,250 to $12,840 cumulative over 10 years. Simulation outcomes suggest reduced
      incidence of diabetes by 27-41% for participants with prediabetes, and stroke by
      approximately 15% over 5 years. CONCLUSIONS: A digital, remotely-delivered IBC
      program can help seniors at risk for diabetes and cardiovascular disease achieve
      significant weight loss, reduces risk for diabetes and cardiovascular disease,
      and achieve meaningful medical cost savings. These findings affirm
      recommendations for IBC coverage by the U.S. Preventive Services Task Force.

PMID- 27706218
TI  - Mapping Long-Term Functional Changes in Cerebral Blood Flow by Arterial Spin
      Labeling.
AB  - Although arterial spin labeling (ASL) is appealing for mapping long-term changes
      in functional activity, inter-sessional variations in basal blood flow, arterial
      transit times (ATTs), and alignment errors, can result in significant false
      activation when comparing images from separate sessions. By taking steps to
      reduce these sources of noise, this study assessed the ability of ASL to detect
      functional CBF changes between sessions. ASL data were collected in three
      sessions to image ATT, resting CBF and CBF changes associated with motor
      activation (7 participants). Activation maps were generated using rest and task
      images acquired in the same session and from sessions separated by up to a month.
      Good agreement was found when comparing between-session activation maps to within
      session activation maps with only a 16% decrease in precision (within-session: 90
      +/- 7%) and a 13% decrease in the Dice similarity (within-session: 0.75 +/- 0.07)
      coefficient after a month. In addition, voxel-wise reproducibility (within
      session: 4.7 +/- 4.5%) and reliability (within-session: 0.89 +/- 0.20) of resting
      grey-matter CBF decreased by less than 18% for the between-session analysis
      relative to within-session values. ATT variability between sessions (5.0 +/-
      2.7%) was roughly half the between-subject variability, indicating that its
      effects on longitudinal CBF were minimal. These results demonstrate that
      conducting voxel-wise analysis on CBF images acquired on different days is
      feasible with only modest loss in precision, highlighting the potential of ASL
      for longitudinal studies.

PMID- 27706219
TI  - Identification of Unanticipated and Novel N-Acyl L-Homoserine Lactones (AHLs)
      Using a Sensitive Non-Targeted LC-MS/MS Method.
AB  - N-acyl L-homoserine lactones (AHLs) constitute a predominant class of quorum
      sensing signaling molecules used by Gram-negative bacteria. Here, we report a
      sensitive and non-targeted HPLC-MS/MS method based on parallel reaction
      monitoring (PRM) to identify and quantitate known, unanticipated, and novel AHLs
      in microbial samples. Using a hybrid quadrupole-high resolution mass analyzer,
      this method integrates MS scans and all-ion fragmentation MS/MS scans to allow
      simultaneous detection of AHL parent-ion masses and generation of full mass
      spectra at high resolution and high mass accuracy in a single chromatographic
      run. We applied this method to screen for AHL production in a variety of Gram
      negative bacteria (i.e. B. cepacia, E. tarda, E. carotovora, E. herbicola, P.
      stewartii, P. aeruginosa, P. aureofaciens, and R. sphaeroides) and discovered
      that nearly all of them produce a larger set of AHLs than previously reported.
      Furthermore, we identified production of an uncommon AHL (i.e. 3-oxo-C7-HL) in E.
      carotovora and P. stewartii, whose production has only been previously observed
      within the genera Serratia and Yersinia. Finally, we used our method to
      quantitate AHL degradation in B. cepacia, E. carotovora, E. herbicola, P.
      stewartii, P. aeruginosa, P. aureofaciens, the non-AHL producer E. coli, and the
      Gram-positive bacterium B. subtilis. We found that AHL degradation ability varies
      widely across these microbes, of which B. subtilis and E. carotovora are the best
      degraders, and observed that there is a general trend for AHLs containing long
      acyl chains (>=10 carbons) to be degraded at faster rates than AHLs with short
      acyl chains (<=6 carbons).

PMID- 27706220
TI  - Anthropometric Study of Three-Dimensional Facial Morphology in Malay Adults.
AB  - OBJECTIVES: To establish the three-dimensional (3D) facial soft tissue morphology
      of adult Malaysian subjects of the Malay ethnic group; and to determine the
      morphological differences between the genders, using a non-invasive stereo
      photogrammetry 3D camera. MATERIAL AND METHODS: One hundred and nine subjects
      participated in this research, 54 Malay men and 55 Malay women, aged 20-30 years
      old with healthy BMI and with no adverse skeletal deviation. Twenty-three facial
      landmarks were identified on 3D facial images captured using a VECTRA M5-360 Head
      System (Canfield Scientific Inc, USA). Two angular, 3 ratio and 17 linear
      measurements were identified using Canfield Mirror imaging software. Intra- and
      inter-examiner reliability tests were carried out using 10 randomly selected
      images, analyzed using the intra-class correlation coefficient (ICC).
      Multivariate analysis of variance (MANOVA) was carried out to investigate
      morphologic differences between genders. RESULTS: ICC scores were generally good
      for both intra-examiner (range 0.827-0.987) and inter-examiner reliability (range
      0.700-0.983) tests. Generally, all facial measurements were larger in men than
      women, except the facial profile angle which was larger in women. Clinically
      significant gender dimorphisms existed in biocular width, nose height, nasal
      bridge length, face height and lower face height values (mean difference > 3mm).
      Clinical significance was set at 3mm. CONCLUSION: Facial soft tissue
      morphological values can be gathered efficiently and measured effectively from
      images captured by a non-invasive stereo-photogrammetry 3D camera. Adult men in
      Malaysia when compared to women had a wider distance between the eyes, a longer
      and more prominent nose and a longer face.

PMID- 27706221
TI  - Modeled Dietary Impact of Pizza Reformulations in US Children and Adolescents.
AB  - BACKGROUND AND OBJECTIVE: Approximately 20% of US children and adolescents
      consume pizza on any given day; and pizza intake is associated with higher
      intakes of energy, sodium, and saturated fat. The reformulation of pizza products
      has yet to be evaluated as a viable option to improve diets of the US youth. This
      study modeled the effect on nutrient intakes of two potential pizza reformulation
      strategies based on the standards established by the Nestle Nutritional Profiling
      System (NNPS). METHODS: Dietary intakes were retrieved from the first 24hr-recall
      of the National Health and Nutrition Examination Survey (NHANES) 2011-12, for
      2655 participants aged 4-19 years. The composition of pizzas in the NHANES food
      database (n = 69) were compared against the NNPS standards for energy, total fat,
      saturated fat, sodium, added sugars, and protein. In a reformulation scenario,
      the nutrient content of pizzas was adjusted to the NNPS standards if these were
      not met. In a substitution scenario, pizzas that did not meet the standards were
      replaced by the closest pizza, based on nutrient content, that met all of the
      NNPS standards. RESULTS: Pizzas consistent with all the NNPS standards (29% of
      all pizzas) were significantly lower in energy, saturated fat and sodium than
      pizzas that were not. Among pizza consumers, modeled intakes in the reformulation
      and substitution scenarios were lower in energy (-14 and -45kcal, respectively),
      saturated fat (-1.2 and -2.7g), and sodium (-143 and -153mg) compared to
      baseline. CONCLUSIONS: Potential industry wide reformulation of a single food
      category or intra-category food substitutions may positively impact dietary
      intakes of US children and adolescents. Further promotion and support of these
      complimentary strategies may facilitate the adoption and implementation of
      reformulation standards.

PMID- 27706222
TI  - Association of Overweight with Food Portion Size among Adults of Sao Paulo -
      Brazil.
AB  - BACKGROUND: Although studies show that portion size affects energy intake, few
      have demonstrated a link between portion size and weight status, especially in
      free-living populations. The objective of the present study was to assess the
      relationship between food portion sizes and overweight in a representative
      population of adults of Sao Paulo, Brazil. METHODS: Cross-sectional population
      based study with 1005 adults from Sao Paulo, Brazil. Dietary data were obtained
      from two 24-hour recalls. Reported foods were classified into groups and energy
      contribution, prevalence of consumers and portion sizes were calculated.
      Individuals were classified according to BMI in with and without overweight.
      Logistic regression models were used to evaluate the association between food
      portion sizes and being overweight. RESULTS: The most consumed food groups were:
      beans, breads/rolls, coffee/tea, milk, rice, and sugar. Rice, red meat,
      breads/rolls, and white meat were the groups with the highest percentage of
      contribution to total energy intake. Butter/margarine, toasts/biscuits, sugar,
      and cakes were the groups with the highest energy density. After adjustment for
      confounding variables, overweight was associated with larger portions of pizza
      (OR = 1.052; p = 0.048), red meat (OR = 1.025; p = 0.043), rice (OR = 1.033;
      p<0.001), salted snacks (OR = 1.078; p = 0.022), and soft drinks (OR = 1.016; p =
      0.007). CONCLUSIONS: Larger portions of few food groups with different energy
      densities were associated with being overweight, suggesting that overweight may
      be related to the consumption of larger portion sizes of a series of food groups,
      not a food group alone. Additionally, we highlight the importance of considering
      underreporting as a confounding factor in these associations.

PMID- 27706223
TI  - Comparative Proteomics Reveals Strain-Specific beta-TrCP Degradation via
      Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex.
AB  - Rotaviruses (RVs) are the leading cause of severe gastroenteritis in young
      children, accounting for half a million deaths annually worldwide. RV encodes non
      structural protein 1 (NSP1), a well-characterized interferon (IFN) antagonist,
      which facilitates virus replication by mediating the degradation of host
      antiviral factors including IRF3 and beta-TrCP. Here, we utilized six human and
      animal RV NSP1s as baits and performed tandem-affinity purification coupled with
      high-resolution mass spectrometry to comprehensively characterize NSP1-host
      protein interaction network. Multiple Cullin-RING ubiquitin ligase (CRL)
      complexes were identified. Importantly, inhibition of cullin-3 (Cul3) or RING-box
      protein 1 (Rbx1), by siRNA silencing or chemical perturbation, significantly
      impairs strain-specific NSP1-mediated beta-TrCP degradation. Mechanistically, we
      demonstrate that NSP1 localizes to the Golgi with the host Cul3-Rbx1 CRL complex,
      which targets beta-TrCP and NSP1 for co-destruction at the proteasome. Our study
      uncovers a novel mechanism that RV employs to promote beta-TrCP turnover and
      provides molecular insights into virus-mediated innate immunity inhibition.

PMID- 27706224
TI  - Comparison of Approaches for Stroke Prophylaxis in Patients with Non-Valvular
      Atrial Fibrillation: Network Meta-Analyses of Randomized Controlled Trials.
AB  - BACKGROUND: Multiple novel oral anticoagulants and left atrial appendage closure
      devices (WATCHMAN) have been tested against dose-adjusted vitamin K antagonists
      in randomized controlled trials for stroke prophylaxis in non-valvular atrial
      fibrillation. No direct comparisons of these strategies are available from
      randomized controlled trials. We conducted the current analyses by combining
      efficacy and safety characteristics of all FDA approved stroke prophylaxis
      treatment strategies for patients with non-valvular atrial fibrillation.
      MATERIALS AND METHODS: We searched SCOPUS from 1945 till October 2015 for
      randomized controlled trials comparing these strategies and reporting efficacy
      and safety outcomes. Six randomized controlled trials were identified and
      included in the final analyses and review. We followed PRISMA guidelines for
      network meta-analyses while reporting the current analyses. We collected data on
      ischemic stroke, major bleeding, and the composite primary safety endpoint as
      defined by various randomized controlled trials. Network meta-analyses were
      conducted using consistency and inconsistency models for efficacy and safety
      outcomes. Surface under the cumulative ranking curve were then utilized to
      cluster rank these treatments for safety and efficacy. RESULTS: Six randomized
      controlled trials with 59,627 patients comparing six treatment strategies were
      eligible for the analyses. All prophylaxis strategies had comparable rates of
      ischemic stroke. Apixaban was associated with the least number of primary safety
      endpoint events as compared with all other treatments. In the cluster analyses
      assessing safety and efficacy, apixaban, edoxaban and dabigatran ranked best
      followed by vitamin K antagonists and rivaroxaban, whereas the WATCHMAN left
      atrial appendage closure device ranked last. CONCLUSIONS: Dose-adjusted vitamin K
      antagonists, novel oral anticoagulants, and the WATCHMAN left atrial appendage
      closure devices are equally efficacious for ischemic stroke prevention but these
      treatments have different safety profiles. More randomized controlled trials are
      needed to directly compare these strategies.

PMID- 27706225
TI  - Examination of the Position Accuracy of Implant Abutments Reproduced by Intra
      Oral Optical Impression.
AB  - An impression technique called optical impression using intraoral scanner has
      attracted attention in digital dentistry. This study aimed to evaluate the
      accuracy of the optical impression, comparing a virtual model reproduced by an
      intraoral scanner to a working cast made by conventional silicone impression
      technique. Two implants were placed on a master model. Working casts made of
      plaster were fabricated from the master model by silicone impression. The
      distance between the ball abutments and the angulation between the healing
      abutments of 5 mm and 7 mm height at master model were measured using Computer
      Numerical Control Coordinate Measuring Machine (CNCCMM) as control. Working casts
      were then measured using CNCCMM, and virtual models via stereo lithography data
      of master model were measured by a three-dimensional analyzing software. The
      distance between ball abutments of the master model was 9634.9 +/- 1.2 MUm. The
      mean values of trueness of the Lava COS and working casts were 64.5 MUm and 22.5
      MUm, respectively, greater than that of control. The mean of precision values of
      the Lava COS and working casts were 15.6 MUm and 13.5 MUm, respectively. In the
      case of a 5-mm-height healing abutment, mean angulation error of the Lava COS was
      greater than that of the working cast, resulting in significant differences in
      trueness and precision. However, in the case of a 7-mm-height abutment, mean
      angulation errors of the Lava COS and the working cast were not significantly
      different in trueness and precision. Therefore, distance errors of the optical
      impression were slightly greater than those of conventional impression. Moreover,
      the trueness and precision of angulation error could be improved in the optical
      impression using longer healing abutments. In the near future, the development of
      information technology could enable improvement in the accuracy of the optical
      impression with intraoral scanners.

PMID- 27706228
TI  - Examination of Surface Deposits on Oldbury Reactor Core Graphite to Determine the
      Concentration and Distribution of 14C.
AB  - Pile Grade A graphite was used as a moderator and reflector material in the first
      generation of UK Magnox nuclear power reactors. As all of these reactors are now
      shut down there is a need to examine the concentration and distribution of long
      lived radioisotopes, such as 14C, to aid in understanding their behaviour in a
      geological disposal facility. A selection of irradiated graphite samples from
      Oldbury reactor one were examined where it was observed that Raman spectroscopy
      can distinguish between underlying graphite and a surface deposit found on
      exposed channel wall surfaces. The concentration of 14C in this deposit was
      examined by sequentially oxidising the graphite samples in air at low
      temperatures (450 degrees C and 600 degrees C) to remove the deposit and then the
      underlying graphite. The gases produced were captured in a series of bubbler
      solutions that were analysed using liquid scintillation counting. It was observed
      that the surface deposit was relatively enriched with 14C, with samples
      originating lower in the reactor exhibiting a higher concentration of 14C.
      Oxidation at 600 degrees C showed that the remaining graphite material consisted
      of two fractions of 14C, a surface associated fraction and a graphite lattice
      associated fraction. The results presented correlate well with previous studies
      on irradiated graphite that suggest there are up to three fractions of 14C; a
      readily releasable fraction (corresponding to that removed by oxidation at 450
      degrees C in this study), a slowly releasable fraction (removed early at 600
      degrees C in this study), and an unreleasable fraction (removed later at 600
      degrees C in this study).

PMID- 27706226
TI  - Fourth-Generation Progestins Inhibit 3beta-Hydroxysteroid Dehydrogenase Type 2
      and Modulate the Biosynthesis of Endogenous Steroids.
AB  - Progestins used in contraception and hormone replacement therapy are synthetic
      compounds designed to mimic the actions of the natural hormone progesterone and
      are classed into four consecutive generations. The biological actions of
      progestins are primarily determined by their interactions with steroid receptors,
      and factors such as metabolism, pharmacokinetics, bioavailability and the
      regulation of endogenous steroid hormone biosynthesis are often overlooked.
      Although some studies have investigated the effects of select progestins on a few
      steroidogenic enzymes, studies comparing the effects of progestins from different
      generations are lacking. This study therefore explored the putative modulatory
      effects of progestins on de novo steroid synthesis in the adrenal by comparing
      the effects of select progestins from the respective generations, on endogenous
      steroid hormone production by the H295R human adrenocortical carcinoma cell line.
      Ultra-performance liquid chromatography/tandem mass spectrometry analysis showed
      that the fourth-generation progestins, nestorone (NES), nomegestrol acetate
      (NoMAC) and drospirenone (DRSP), unlike the progestins selected from the first
      three generations, modulate the biosynthesis of several endogenous steroids.
      Subsequent assays performed in COS-1 cells expressing human 3betaHSD2, suggest
      that these progestins modulate the biosynthesis of steroid hormones by inhibiting
      the activity of 3betaHSD2. The Ki values determined for the inhibition of human
      3betaHSD2 by NES (9.5 +/- 0.96 nM), NoMAC (29 +/- 7.1 nM) and DRSP (232 +/- 38
      nM) were within the reported concentration ranges for the contraceptive use of
      these progestins in vivo. Taken together, our results suggest that newer, fourth
      generation progestins may exert both positive and negative physiological effects
      via the modulation of endogenous steroid hormone biosynthesis.

PMID- 27706227
TI  - Thermal Preference Ranges Correlate with Stable Signals of Universal Stress
      Markers in Lake Baikal Endemic and Holarctic Amphipods.
AB  - Temperature is the most pervasive abiotic environmental factor for aquatic
      organisms. Fluctuations in temperature range lead to changes in metabolic
      performance. Here, we aimed to identify whether surpassing the thermal preference
      zones is correlated with shifts in universal cellular stress markers of protein
      integrity, responses to oxidative stress and lactate content, as indicators of
      anaerobic metabolism. Exposure of the Lake Baikal endemic amphipod species
      Eulimnogammarus verrucosus (Gerstfeldt, 1858), Ommatogammarus flavus (Dybowski,
      1874) and of the Holarctic amphipod Gammarus lacustris Sars 1863 (Amphipoda,
      Crustacea) to increasing temperatures resulted in elevated heat shock protein 70
      (Hsp70) and lactate content, elevated antioxidant enzyme activities (i.e.,
      catalase and peroxidase), and reduced lactate dehydrogenase and glutathione S
      transferase activities. Thus, the zone of stability (absence of any significant
      changes) of the studied molecular and biochemical markers correlated with the
      behaviorally preferred temperatures. We conclude that the thermal behavioral
      responses of the studied amphipods are directly related to metabolic processes at
      the cellular level. Thus, the determined thermal ranges may possibly correspond
      to the thermal optima. This relationship between species-specific behavioral
      reactions and stress response metabolism may have significant ecological
      consequences that result in a thermal zone-specific distribution (i.e., depths,
      feed spectrum, etc.) of species. As a consequence, by separating species with
      different temperature preferences, interspecific competition is reduced, which,
      in turn, increases a species' Darwinian fitness in its environment.

PMID- 27706229
TI  - Management-Related Traffic as a Stressor Eliciting Parental Care in a Roadside
      Nesting Bird: The European Bee-Eater Merops apiaster.
AB  - Traffic is often acknowledged as a threat to biodiversity, but its effects have
      been mostly studied on roads subjected to high traffic intensity. The impact of
      lower traffic intensity such as those affecting protected areas is generally
      neglected, but conservation-oriented activities entailing motorized traffic could
      paradoxically transform suitable habitats into ecological traps. Here we
      questioned whether roadside-nesting bee-eaters Merops apiaster perceived low
      traffic intensity as a stressor eliciting risk-avoidance behaviors (alarm calls
      and flock flushes) and reducing parental care. Comparisons were established
      within Donana National Park (Spain), between birds exposed to either negligible
      traffic (ca. 0-10 vehicles per day) or low traffic intensity (ca. 10-90 vehicles
      per day) associated to management and research activities. The frequencies of
      alarm calls and flock flushes were greater in areas of higher traffic intensity,
      which resulted in direct mortality at moderate vehicle speeds (<= 40 km/h).
      Parental feeding rates paralleled changes in traffic intensity, but contrary to
      our predictions. Indeed, feeding rates were highest in traffic-exposed nests,
      during working days and traffic rush-hours. Traffic-avoidance responses were
      systematic and likely involved costs (energy expenditure and mortality), but
      vehicle transit positively influenced the reproductive performance of bee-eaters
      through an increase of nestling feeding rates. Because the expected outcome of
      traffic on individual performance can be opposed when responses are monitored
      during mating (i.e. negative effect by increase of alarm calls and flock flushes)
      or nestling-feeding period (i.e. at least short-term positive effect by increase
      of nestling feeding rates), caution should be taken before inferring fitness
      consequences only from isolated behaviors or specific life history stages.

PMID- 27706230
TI  - Using Survival Analysis to Identify Risk Factors for Treatment Interruption among
      New and Retreatment Tuberculosis Patients in Kenya.
AB  - Despite high tuberculosis (TB) treatment success rate, treatment adherence is one
      of the major obstacles to tuberculosis control in Kenya. Our objective was to
      identify patient-related factors that were associated with time to TB treatment
      interruption and the geographic distribution of the risk of treatment
      interruption by county. Data of new and retreatment patients registered in TIBU,
      a Kenyan national case-based electronic data recording system, between 2013 and
      2014 was obtained. Kaplan-Meier curves and log rank tests were used to assess the
      adherence patterns. Mixed-effects Cox proportional hazards modeling was used for
      multivariate analysis. Records from 90,170 patients were included in the study.
      The cumulative incidence of treatment interruption was 4.5% for new patients, and
      8.5% for retreatment patients. The risk of treatment interruption was highest
      during the intensive phase of treatment. Having previously been lost to follow-up
      was the greatest independent risk factor for treatment interruption (HR: 4.79
      [3.99, 5.75]), followed by being HIV-positive not on ART (HR: 1.96 [1.70, 2.26])
      and TB relapse (HR: 1.70 [1.44, 2.00]). Male and underweight patients had high
      risks of treatment interruption (HR: 1.46 [1.35, 1.58]; 1.11 [1.03, 1.20],
      respectively). High rates of treatment interruption were observed in counties in
      the central part of Kenya while counties in the northeast had the lowest risk of
      treatment interruption. A better understanding of treatment interruption risk
      factors is necessary to improve adherence to treatment. Interventions should
      focus on patients during the intensive phase, patients who have previously been
      lost to follow-up, and promotion of integrated TB and HIV services among public
      and private facilities.

PMID- 27706231
TI  - Protective Effects of Acetylation on the Pathological Reactions of the Lens
      Crystallins with Homocysteine Thiolactone.
AB  - Various post-translational lens crystallins modifications result in structural
      and functional insults, contributing to the development of lens opacity and
      cataract disorders. Lens crystallins are potential targets of homocysteinylation,
      particularly under hyperhomocysteinemia which has been indicated in various eye
      diseases. Since both homocysteinylation and acetylation primarily occur on
      protein free amino groups, we applied different spectroscopic methods and gel
      mobility shift analysis to examine the possible preventive role of acetylation
      against homocysteinylation. Lens crystallins were extensively acetylated in the
      presence of acetic anhydride and then subjected to homocysteinylation in the
      presence of homocysteine thiolactone (HCTL). Extensive acetylation of the lens
      crystallins results in partial structural alteration and enhancement of their
      stability, as well as improvement of alpha-crystallin chaperone-like activity. In
      addition, acetylation partially prevents HCTL-induced structural alteration and
      aggregation of lens crystallins. Also, acetylation protects against HCTL-induced
      loss of alpha-crystallin chaperone activity. Additionally, subsequent acetylation
      and homocysteinylation cause significant proteolytic degradation of crystallins.
      Therefore, further experimentation is required in order to judge effectively the
      preventative role of acetylation on the structural and functional insults induced
      by homocysteinylation of lens crystallins.

PMID- 27706232
TI  - Cadmium-109 Radioisotope Adsorption onto Polypyrrole Coated Sawdust of
      Dryobalanops aromatic: Kinetics and Adsorption Isotherms Modelling.
AB  - A radiotracer study was conducted to investigate the removal characteristics of
      cadmium (109Cd) from aqueous solution by polypyrrole/ sawdust composite. Several
      factors such as solution pH, sorbent dosage, initial concentration, contact time,
      temperature and interfering metal ions were found to have influence on the
      adsorption process. The kinetics of adsorption was relatively fast, reaching
      equilibrium within 3 hours. A lowering of the solution pH reduced the removal
      efficiency from 99.3 to ~ 46.7% and an ambient temperature of 25 degrees C was
      found to be optimum for maximum adsorption. The presence of sodium and potassium
      ions inhibited 109Cd removal from its aqueous solution. The experimental data for
      109Cd adsorption showed a very good agreement with the Langmuir isotherm and a
      pseudo-first order kinetic model. The surface condition of the adsorbent before
      and after cadmium loading was investigated using BET, FESEM and FTIR. Considering
      the low cost of the precursor's materials and the toxicity of 109Cd radioactive
      metal, polypyrrole synthesized on the sawdust of Dryobalanops aromatic could be
      used as an efficient adsorbent for the removal of 109Cd radioisotope from
      radionuclide-containing effluents.

PMID- 27706233
TI  - Dysregulation of Autophagy Contributes to Anal Carcinogenesis.
AB  - INTRODUCTION: Autophagy is an intracellular catabolic process that removes and
      recycles unnecessary/dysfunctional cellular components, contributing to cellular
      health and survival. Autophagy is a highly regulated cellular process that
      responds to several intracellular signals, many of which are deregulated by human
      papillomavirus (HPV) infection through the expression of HPV-encoded
      oncoproteins. This adaptive inhibitory response helps prevent viral clearance. A
      strong correlation remains between HPV infection and the development of squamous
      cell carcinoma (SCC) of the anus, particularly in HIV positive and other
      immunosuppressed patients. We hypothesize that autophagy is inhibited by HPV
      encoded oncoproteins thereby promoting anal carcinogenesis (Fig 1). MATERIALS AND
      METHODS: HPV16 transgenic mice (K14E6/E7) and non-transgenic mice (FVB/N), both
      of which do not spontaneously develop anal tumors, were treated topically with
      the chemical carcinogen, 7,12-Dimethylbenz[a]anthracene (DMBA), to induce anal
      cancer. The anuses at different time points of treatment (5, 10, 15 and 20 weeks)
      were analyzed using immunofluorescence (IF) for two key autophagy marker proteins
      (LC3beta and p62) in addition to histological grading. The anuses from the
      K14E6/E7 mice were also analyzed for visual evidence of autophagic activity by
      electron microscopy (EM). To see if there was a correlation to humans, archival
      anal specimens were assessed histologically for grade of dysplasia and then
      analyzed for LC3beta and p62 protein content. To more directly examine the effect
      of autophagic inhibition on anal carcinogenesis, nontransgenic mice that do not
      develop anal cancer with DMBA treatment were treated with a known pharmacologic
      inhibitor of autophagy, chloroquine, and examined for tumor development and
      analyzed by IF for autophagic proteins. RESULTS: Histologically, we observed the
      progression of normal anoderm to invasive SCC with DMBA treatment in K14E6/E7
      mice but not in nontransgenic, syngeneic FVB/N background control mice. With the
      development of low-grade dysplasia in the K14E6/E7 mice, there was an increase in
      both punctate LC3beta and p62 expression while EM revealed increased
      autophagosomes without evidence of autophagolysosomes. These observations are
      consistent with autophagy being inhibited at a later stage in the autophagic
      process. In contrast, in high-grade dysplasia and SCC in the DMBA-treated
      K14E6/E7 mice, there were decreased levels of p62 with a continued increase in
      punctate LC3beta expression by IF, while autophagolysosomes were seen on EM,
      consistent with the process of autophagy proceeded to completion. Similar
      findings, including histological grade dependent changes in LC3beta and p62
      expression, were noted with human samples upon analysis of IF. Finally, with
      pharmacologic inhibition of autophagy in DMBA-treated, nontrangenic FVB/N mice,
      there was a significant increase in anal cancer development similar to that
      observed in DMBA- treated K14E6/E7 mice. CONCLUSION: Autophagic dysregulation is
      noted early on in HPV-associated anal carcinogenesis (low-grade dysplasia), with
      normalization of the autophagic process arising in late stages of HPV-associated
      anal carcinogenesis (high-grade dysplasia and invasive carcinoma).

PMID- 27706234
TI  - Optimizing the Learning Order of Chinese Characters Using a Novel Topological
      Sort Algorithm.
AB  - We present a novel algorithm for optimizing the order in which Chinese characters
      are learned, one that incorporates the benefits of learning them in order of
      usage frequency and in order of their hierarchal structural relationships. We
      show that our work outperforms previously published orders and algorithms. Our
      algorithm is applicable to any scheduling task where nodes have intrinsic
      differences in importance and must be visited in topological order.

PMID- 27706237
TI  - Inducible Expression of the De-Novo Designed Antimicrobial Peptide SP1-1 in
      Tomato Confers Resistance to Xanthomonas campestris pv. vesicatoria.
AB  - Antimicrobial peptides (AMPs) are small peptides with less than 50 amino acids
      and are part of the innate immune response in almost all organisms, including
      bacteria, vertebrates, invertebrates and plants. AMPs are active against a broad
      spectrum of pathogens. The inducible expression of AMPs in plants is a promising
      approach to combat plant pathogens with minimal negative side effects, such as
      phytotoxicity or infertility. In this study, inducible expression of the de-novo
      designed AMP SP1-1 in Micro Tom tomato protected tomato fruits against bacterial
      spot disease caused by Xanthomonas campestris pv. vesicatoria. The peptide SP1-1
      was targeted to the apoplast which is the primary infection site for plant
      pathogens, by fusing SP1-1 peptide to the signal peptide RsAFP1 of radish
      (Raphanus sativus). The pathogen inducibility of the expression was enabled by
      using an optimized inducible 4XW2/4XS promoter. As a result, the tomato fruits of
      independently generated SP1-1 transgenic lines were significantly more resistant
      to X. campestris pv. vesicatoria than WT tomato fruits. In transgenic lines,
      bacterial infection was reduced up to 65% in comparison to the infection of WT
      plants. Our study demonstrates that the combination of the 4XW2/4XS cis-element
      from parsley with the synthetic antimicrobial peptide SP1-1 is a good alternative
      to protect tomato fruits against infections with X. campestris pv. vesicatoria.

PMID- 27706236
TI  - RNA-Seq of Borrelia burgdorferi in Multiple Phases of Growth Reveals Insights
      into the Dynamics of Gene Expression, Transcriptome Architecture, and Noncoding
      RNAs.
AB  - Borrelia burgdorferi, the agent of Lyme disease, differentially expresses
      numerous genes and proteins as it cycles between mammalian hosts and tick
      vectors. Insights on regulatory mechanisms have been provided by earlier studies
      that examined B. burgdorferi gene expression patterns during cultivation.
      However, prior studies examined bacteria at only a single time point of
      cultivation, providing only a snapshot of what is likely a dynamic
      transcriptional program driving B. burgdorferi adaptations to changes during
      culture growth phases. To address that concern, we performed RNA sequencing (RNA
      Seq) analysis of B. burgdorferi cultures at early-exponential, mid-exponential,
      and early-stationary phases of growth. We found that expression of nearly 18% of
      annotated B. burgdorferi genes changed significantly during culture maturation.
      Moreover, genome-wide mapping of the B. burgdorferi transcriptome in different
      growth phases enabled insight on transcript boundaries, operon structures, and
      identified numerous putative non-coding RNAs. These RNA-Seq data are discussed
      and presented as a resource for the community of researchers seeking to better
      understand B. burgdorferi biology and pathogenesis.

PMID- 27706235
TI  - Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of
      Alzheimer's Disease Patients.
AB  - OBJECTIVES: Older familial caregivers of Alzheimer's disease patients are
      subjected to stress-related cognitive and psychophysiological dysfunctions that
      may affect their quality of life and ability to provide care. Younger caregivers
      have never been properly evaluated. We hypothesized that they would show
      qualitatively similar cognitive and psychophysiological alterations to those of
      older caregivers. METHOD: The cognitive measures of 17 young (31-58 years) and 18
      old (63-84 years) caregivers and of 17 young (37-57 years) and 18 old (62-84
      years) non-caregiver controls were evaluated together with their salivary
      cortisol and dehydroepiandrosterone (DHEA) levels, as measured by
      radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in
      serum. RESULTS: Although younger caregivers had milder impairments in memory and
      executive functions than older caregivers, their performances fell to the same or
      lower levels as those of the healthy older controls. Decreases in DHEA and BDNF
      levels were correlated with the cognitive dysfunctions observed in the older and
      younger caregivers, respectively. Cortisol at 10PM increased in both caregiver
      groups. DISCUSSION: Younger caregivers were prone to cognitive impairments
      similar to older caregivers, although the degree and the neuropsychological
      correlates of the cognitive dysfunctions were somewhat different between the two
      groups. This work has implications for caregiver and care-recipient health and
      for research on the neurobiology of stress-related cognitive dysfunctions.

PMID- 27706238
TI  - Involvement of the NLRC4-Inflammasome in Diabetic Nephropathy.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease
      worldwide but current treatments remain suboptimal. The role of inflammation in
      DN has only recently been recognized. It has been shown that the NLRP3
      inflammasome contributes to DN development by inducing interleukin (IL)-1beta
      processing and secretion. In an effort to understand other IL-1beta activating
      mechanism during DN development, we examined the role of the NLRC4-inflammasome
      in DN and found that NLRC4 is a parallel mechanism, in addition to the NLRP3
      inflammasome, to induce pro-IL-1beta processing and activation. We found that the
      expression of NLRC4 is elevated in DN kidneys. NLRC4-deficiency results in
      diminished DN disease progression, as manifested by a decrease in blood glucose
      and albumin excretion, as well as preserved renal histology. We further found
      that DN kidneys have increased F4/80+ macrophages, increased IL-1beta production,
      and other signaling pathways related to kidney pathology such as activation of NF
      kappaB and MAP kinase pathways, all of which were rescued by NLRC4-deficiency.
      This study demonstrates NLRC4-driven IL-1beta production as critical for the
      progression of DN, which underscores the importance to target this pathway to
      alleviate this devastating disease.

PMID- 27706239
TI  - Spatial and Temporal Resolution of Global Protein Synthesis during HSV Infection
      Using Bioorthogonal Precursors and Click Chemistry.
AB  - We used pulse-labeling with the methionine analogue homopropargylglycine (HPG) to
      investigate spatiotemporal aspects of protein synthesis during herpes simplex
      virus (HSV) infection. In vivo incorporation of HPG enables subsequent selective
      coupling of fluorochrome-capture reagents to newly synthesised proteins. We
      demonstrate that HPG labeling had no effect on cell viability, on accumulation of
      test early or late viral proteins, or on overall virus yields. HPG pulse-labeling
      followed by SDS-PAGE analysis confirmed incorporation into newly synthesised
      proteins, while parallel processing by in situ cycloaddition revealed new insight
      into spatiotemporal aspects of protein localisation during infection. A striking
      feature was the rapid accumulation of newly synthesised proteins not only in a
      general nuclear pattern but additionally in newly forming sub-compartments
      represented by small discrete foci. These newly synthesised protein domains
      (NPDs) were similar in size and morphology to PML domains but were more numerous,
      and whereas PML domains were progressively disrupted, NPDs were progressively
      induced and persisted. Immediate-early proteins ICP4 and ICP0 were excluded from
      NPDs, but using an ICP0 mutant defective in PML disruption, we show a clear
      spatial relationship between NPDs and PML domains with NPDs frequently forming
      immediately adjacent and co-joining persisting PML domains. Further analysis of
      location of the chaperone Hsc70 demonstrated that while NPDs formed early in
      infection without overt Hsc70 recruitment, later in infection Hsc70 showed
      pronounced recruitment frequently in a coat-like fashion around NPDs. Moreover,
      while ICP4 and ICP0 were excluded from NPDs, ICP22 showed selective recruitment.
      Our data indicate that NPDs represent early recruitment of host and viral de novo
      translated protein to distinct structural entities which are precursors to the
      previously described VICE domains involved in protein quality control in the
      nucleus, and reveal new features from which we propose spatially linked platforms
      of newly synthesised protein processing after nuclear import.

PMID- 27706240
TI  - Retrospective Attention Interacts with Stimulus Strength to Shape Working Memory
      Performance.
AB  - Orienting attention retrospectively to selective contents in working memory (WM)
      influences performance. A separate line of research has shown that stimulus
      strength shapes perceptual representations. There is little research on how
      stimulus strength during encoding shapes WM performance, and how effects of
      retrospective orienting might vary with changes in stimulus strength. We explore
      these questions in three experiments using a continuous-recall WM task. In
      Experiment 1 we show that benefits of cueing spatial attention retrospectively
      during WM maintenance (retrocueing) varies according to stimulus contrast during
      encoding. Retrocueing effects emerge for supraliminal but not sub-threshold
      stimuli. However, once stimuli are supraliminal, performance is no longer
      influenced by stimulus contrast. In Experiments 2 and 3 we used a mixture-model
      approach to examine how different sources of error in WM are affected by contrast
      and retrocueing. For high-contrast stimuli (Experiment 2), retrocues increased
      the precision of successfully remembered items. For low-contrast stimuli
      (Experiment 3), retrocues decreased the probability of mistaking a target with
      distracters. These results suggest that the processes by which retrospective
      attentional orienting shape WM performance are dependent on the quality of WM
      representations, which in turn depends on stimulus strength during encoding.

PMID- 27706241
TI  - Intensity Thresholds on Raw Acceleration Data: Euclidean Norm Minus One (ENMO)
      and Mean Amplitude Deviation (MAD) Approaches.
AB  - OBJECTIVES: (1) To develop and internally-validate Euclidean Norm Minus One
      (ENMO) and Mean Amplitude Deviation (MAD) thresholds for separating sedentary
      behaviours from common light-intensity physical activities using raw acceleration
      data collected from both hip- and wrist-worn tri-axial accelerometers; and (2) to
      compare and evaluate the performances between the ENMO and MAD metrics. METHODS:
      Thirty-three adults [mean age (standard deviation (SD)) = 27.4 (5.9) years; mean
      BMI (SD) = 23.9 (3.7) kg/m2; 20 females (60.6%)] wore four accelerometers; an
      ActiGraph GT3X+ and a GENEActiv on the right hip; and an ActiGraph GT3X+ and a
      GENEActiv on the non-dominant wrist. Under laboratory-conditions, participants
      performed 16 different activities (11 sedentary behaviours and 5 light-intensity
      physical activities) for 5 minutes each. ENMO and MAD were computed from the raw
      acceleration data, and logistic regression and receiver-operating-characteristic
      (ROC) analyses were implemented to derive thresholds for activity discrimination.
      Areas under ROC curves (AUROC) were calculated to summarise performances and
      thresholds were assessed via executing leave-one-out-cross-validations. RESULTS:
      For both hip and wrist monitor placements, in comparison to the ActiGraph GT3X+
      monitors, the ENMO and MAD values derived from the GENEActiv devices were
      observed to be slightly higher, particularly for the lower-intensity activities.
      Monitor-specific hip and wrist ENMO and MAD thresholds showed excellent ability
      for separating sedentary behaviours from motion-based light-intensity physical
      activities (in general, AUROCs >0.95), with validation indicating robustness.
      However, poor classification was experienced when attempting to isolate standing
      still from sedentary behaviours (in general, AUROCs <0.65). The ENMO and MAD
      metrics tended to perform similarly across activities and accelerometer brands.
      CONCLUSIONS: Researchers can utilise these robust monitor-specific hip and wrist
      ENMO and MAD thresholds, in order to accurately separate sedentary behaviours
      from common motion-based light-intensity physical activities. However, caution
      should be taken if isolating sedentary behaviours from standing is of particular
      interest.

PMID- 27706242
TI  - The Significance of Serum HER2 Levels at Diagnosis on Intrinsic Subtype-Specific
      Outcome of Operable Breast Cancer Patients.
AB  - PURPOSE: This study evaluated the association of serum HER2 (sHER2) levels at
      diagnosis with clinicopathologic parameters and disease free survival (DFS) in
      operable breast cancer patients according to intrinsic subtype. METHODS: The
      sHER2 levels were measured using a chemiluminescence immunoassay. The HER2 status
      in all tumor tissues was determined by immunohistochemistry, and confirmed in
      equivocal cases by fluorescence in situ. RESULTS: There were 436 consecutive
      stage I-III breast cancer patients with sHER2 result at diagnosis between Nov
      2004 and Dec 2011. High sHER2 levels (>= 15 ng/ml) were reported in 52 patients
      (11.9%) and HER2 overexpression in tumor tissue was observed in 111 patients
      (25.5%). High sHER2 levels were associated significantly with advanced stage (P <
      0.001), mastectomy (P = 0.012), neoadjuvant chemotherapy (P < 0.001), anti-HER2
      therapy (P < 0.001) and hormone therapy (P = 0.022). The patients with high sHER2
      levels had a worse DFS (P < 0.001). In multivariate analysis, high sHER2 levels
      were associated significantly with worse DFS (HR = 2.25, 95% CI 1.27-3.99, P =
      0.005). High sHER2 levels were associated with worse DFS in the HR+/HER2-,
      HR+/HER2+ and HR-/HER2+ subtypes (P = 0.043, 0.003 and 0.041, respectively).
      CONCLUSIONS: These results show that the sHER2 level at diagnosis is a useful
      prognostic factor in patients with operable breast cancer, especially in the
      HR+/HER2-, HR+/HER2+ and HR-/HER2+ subtypes.

PMID- 27706243
TI  - Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI)
      in Patients with Small Cell Lung Cancer_ Comparison with Original ALI.
AB  - BACKGROUND: Advanced lung cancer inflammation index (ALI, body mass index [BMI] x
      serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict
      overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal
      muscle to be quantified, whereas BMI cannot accurately reflect body composition.
      The purpose was to evaluate prognostic value of modified ALI (mALI) using CT
      determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI.
      METHODS: L3MIs were calculated using the CT images of 186 consecutive patients
      with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR.
      Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the
      prognostic values of low ALI and low mALI were tested using Kaplan-Meier method
      and Cox proportional hazards analysis. Finally, deviance statistics was used to
      test whether the goodness of fit of the prognostic model is improved by adding
      mALI as an extra variable. RESULTS: Patients with low ALI (cut-off, 31.1, n = 94)
      had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p
      < 0.001), and patients with low mALI (cut-off 67.7, n = 94) had shorter OS than
      patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001). There
      was no significant difference in estimates of median survival time between low
      ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z =
      0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent
      prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age
      (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p < 0.001), supportive care
      only (HR, 7.86, p < 0.001), and elevated LDH (HR, 1.45, p = 0.037). Furthermore,
      goodness of fit of this prognostic model was not significantly increased by
      adding mALI as an extra variable (LR difference = 2.220, p = 0.136). CONCLUSION:
      The present study confirms mALI using CT-determined L3MI has no additional
      prognostic value beyond original ALI using BMI. ALI is a simple and useful
      prognostic indicator in SCLC.

PMID- 27706244
TI  - A Specially Designed Multi-Gene Panel Facilitates Genetic Diagnosis in Children
      with Intrahepatic Cholestasis: Simultaneous Test of Known Large
      Insertions/Deletions.
AB  - BACKGROUND AND AIMS: Large indels are commonly identified in patients but are not
      detectable by routine Sanger sequencing and panel sequencing. We specially
      designed a multi-gene panel that could simultaneously test known large indels in
      addition to ordinary variants, and reported the diagnostic yield in patients with
      intrahepatic cholestasis. METHODS: The panel contains 61 genes associated with
      cholestasis and 25 known recurrent large indels. The amplicon library was
      sequenced on Ion PGM system. Sequencing data were analyzed using a routine data
      analysis protocol and an internal program encoded for large indels test
      simultaneously. The validation phase was performed using 54 patients with known
      genetic diagnosis, including 5 with large insertions. At implement phase, 141
      patients with intrahepatic cholestasis were evaluated. RESULTS: At validation
      phase, 99.6% of the variations identified by Sanger sequencing could be detected
      by panel sequencing. Following the routine protocol, 99.8% of false positives
      could be filtered and 98.8% of retained variations were true positives. Large
      insertions in the 5 patients with known genetic diagnosis could be correctly
      detected using the internal program. At implementation phase, 96.9% of the
      retained variations, following the routine protocol, were confirmed to be true.
      Twenty-nine patients received a potential genetic diagnosis when panel sequencing
      data were analyzed using the routine protocol. Two additional patients, who were
      found to harbor large insertions in SLC25A13, obtained a potential genetic
      diagnosis when sequencing data were further analyzed using the internal program.
      A total of 31 (22.0%) patients obtained a potential genetic diagnosis. Nine
      different genetic disorders were diagnosed, and citrin deficiency was the
      commonest. CONCLUSION: Specially designed multi-gene panel can correctly detect
      large indels simultaneously. By using it, we assigned a potential genetic
      diagnosis to 22.0% of patients with intrahepatic cholestasis.

PMID- 27706245
TI  - Characteristics of Retractions from Korean Medical Journals in the KoreaMed
      Database: A Bibliometric Analysis.
AB  - BACKGROUND: Flawed or misleading articles may be retracted because of either
      honest scientific errors or scientific misconduct. This study explored the
      characteristics of retractions in medical journals published in Korea through the
      KoreaMed database. METHODS: We retrieved retraction articles indexed in the
      KoreaMed database from January 1990 to January 2016. Three authors each reviewed
      the details of the retractions including the reason for retraction, adherence to
      retraction guidelines, and appropriateness of retraction. Points of disagreement
      were reconciled by discussion among the three. RESULTS: Out of 217,839 articles
      in KoreaMed published from 1990 to January 2016, the publication type of 111
      articles was retraction (0.051%). Of the 111 articles (addressing the retraction
      of 114 papers), 58.8% were issued by the authors, 17.5% were jointly issued
      (author, editor, and publisher), 15.8% came from editors, and 4.4% were
      dispatched by institutions; in 5.3% of the instances, the issuer was unstated.
      The reasons for retraction included duplicate publication (57.0%), plagiarism
      (8.8%), scientific error (4.4%), author dispute (3.5%), and other (5.3%); the
      reasons were unstated or unclear in 20.2%. The degree of adherence to COPE's
      retraction guidelines varied (79.8%-100%), and some retractions were
      inappropriate by COPE standards. These were categorized as follows: retraction of
      the first published article in the case of duplicate publication (69.2%),
      authorship dispute (15.4%), errata (7.7%), and other (7.7%). CONCLUSION: The
      major reason for retraction in Korean medical journals is duplicate publication.
      Some retractions resulted from overreaction by the editors. Therefore, editors of
      Korean medical journals should take careful note of the COPE retraction
      guidelines and should undergo training on appropriate retraction practices.

PMID- 27706246
TI  - Extracellular Histone Released from Leukemic Cells Increases Their Adhesion to
      Endothelium and Protects them from Spontaneous and Chemotherapy-Induced Leukemic
      Cell Death.
AB  - INTRODUCTION: When leukocytes are stimulated by reactive oxygen species (ROS),
      they release nuclear contents into the extracellular milieu, called by
      extracellular traps (ET). The nuclear contents are mainly composed of the histone
      DNA complex and neutrophil elastase. This study investigated whether leukemic
      cells could release ET and the released histone could induce endothelial
      activation, eventually resulting in leukemic progression. METHODS: The
      circulating ET were measured in 80 patients with hematologic diseases and 40
      healthy controls. ET formation and ROS levels were investigated during leukemic
      cell proliferation in vitro. Histone-induced endothelial adhesion molecules
      expression and cell survival were measured by flow cytometry. RESULTS: Acute
      leukemia patients had high levels of ET, which correlated with peripheral blast
      count. Leukemic cells produced high ROS levels and released extracellular
      histone, which was significantly blocked by antioxidants. Histone significantly
      induced 3 endothelial adhesion molecules expression, and promoted leukemic cell
      adhesion to endothelial cells, which was inhibited by histone inhibitors
      (heparin, polysialic acid, and activated protein C), neutralizing antibodies
      against these adhesion molecules, and a Toll like receptor(TLR)9 antagonist. When
      leukemic cells were co-cultured with endothelial cells, adherent leukemic cells
      showed better survival than the non-adherent ones, demonstrating that histone
      treated endothelial cells protected leukemic cells from both spontaneous and
      chemotherapy-induced death. CONCLUSION: Our data demonstrate for the first time
      that extracellular histone can be released from leukemic cells through a ROS
      dependent mechanism. The released histone promotes leukemic cell adhesion by
      inducting the surface expression of endothelial adhesion molecules and eventually
      protects leukemic cells from cell death.

PMID- 27706248
TI  - Democratizing Neurorehabilitation: How Accessible are Low-Cost Mobile-Gaming
      Technologies for Self-Rehabilitation of Arm Disability in Stroke?
AB  - Motor-training software on tablets or smartphones (Apps) offer a low-cost, widely
      available solution to supplement arm physiotherapy after stroke. We assessed the
      proportions of hemiplegic stroke patients who, with their plegic hand, could
      meaningfully engage with mobile-gaming devices using a range of standard control
      methods, as well as by using a novel wireless grip-controller, adapted for
      neurodisability. We screened all newly-diagnosed hemiplegic stroke patients
      presenting to a stroke centre over 6 months. Subjects were compared on their
      ability to control a tablet or smartphone cursor using: finger-swipe, tap,
      joystick, screen-tilt, and an adapted handgrip. Cursor control was graded as: no
      movement (0); less than full-range movement (1); full-range movement (2);
      directed movement (3). In total, we screened 345 patients, of which 87 satisfied
      recruitment criteria and completed testing. The commonest reason for exclusion
      was cognitive impairment. Using conventional controls, the proportion of patients
      able to direct cursor movement was 38-48%; and to move it full-range was 55-67%
      (controller comparison: p>0.1). By comparison, handgrip enabled directed control
      in 75%, and full-range movement in 93% (controller comparison: p<0.001). This
      difference between controllers was most apparent amongst severely-disabled
      subjects, with 0% achieving directed or full-range control with conventional
      controls, compared to 58% and 83% achieving these two levels of movement,
      respectively, with handgrip. In conclusion, hand, or arm, training Apps played on
      conventional mobile devices are likely to be accessible only to mildly-disabled
      stroke patients. Technological adaptations such as grip-control can enable more
      severely affected subjects to engage with self-training software.

PMID- 27706247
TI  - Nasopharyngeal Pneumococcal Carriage among Healthy Children in Cyprus Post
      Widespread Simultaneous Implementation of PCV10 and PCV13 Vaccines.
AB  - The objective of the study was to describe the incidence of pneumococcal
      nasopharyngeal carriage, serotype distribution and antibiotic resistance profile
      of pneumococcal nasopharyngeal isolates in healthy children aged 6 to 36 months
      following the implementation of conjugate vaccines. A nasopharyngeal swab was
      collected from 1105 healthy children following a stratified random sampling
      between September 2013 and April 2014. Demographics, vaccination status and data
      on possible risk factors were recorded. Isolates were serotyped and tested for
      antibiotic susceptibility. The nasopharyngeal carriage rate was 25.3%. Among 1105
      children enrolled, 393 had received PCV13 and 685 PCV10. The prevailing isolated
      serotypes were: 23A (14.3%), 15A (8.9%), 6C (8.6%), 23B (7.5%), 19A (5.4%) and
      15B (5%). The proportion of non-vaccine serotypes, PCV10 serotypes, PCV13
      additional serotypes (3, 6A, 19A) was 76.8%, 2.1% and 10.4% respectively.
      Although children, who were fully or partially vaccinated with PCV13, were 63%
      less likely to be colonized with additional PCV13 serotypes compared to those
      vaccinated with PCV10, the difference is not significant (95%Cl = 0.14-1.02, p =
      0.053). The highest antibiotic non-susceptible rates were found for erythromycin
      (28.2%) and penicillin (27.9%). The overall multidrug resistance rate was 13.2%,
      with serotypes 24F (4/6), 15A (14/25) and 19A (6/15) being the main contributors.
      Carriage rate was similar between children vaccinated with PCV10 or PCV13. The
      high incidence of 15A serotype which is also multidrug resistant should be
      underlined. Ongoing surveillance is needed to monitor the dynamics on
      nasopharyngeal carriage.

PMID- 27706249
TI  - Carbon Costs of Constitutive and Expressed Resistance to a Non-Native Pathogen in
      Limber Pine.
AB  - Increasing the frequency of resistance to the non-native fungus Cronartium
      ribicola (causative agent of white pine blister rust, WPBR) in limber pine
      populations is a primary management objective to sustain high-elevation forest
      communities. However, it is not known to what extent genetic disease resistance
      is costly to plant growth or carbon economy. In this study, we measured growth
      and leaf-level physiology in (1) seedling families from seed trees that have
      previously been inferred to carry or not carry Cr4, the dominant R gene allele
      conferring complete, gene-for-gene resistance to WPBR in limber pine, and (2)
      populations that were and were not infected with C. ribicola. We found that, in
      the absence of C. ribicola exposure, there was no significant difference in
      carbon relations between families born from seed trees that harbor the resistance
      allele compared to those that lack it, either to plant growth and phenology or
      leaf-level photosynthetic traits. However, post-infection with C. ribicola,
      growth was significantly reduced in inoculation survivors expressing complete
      resistance compared to uninoculated seedlings. Furthermore, inoculation survivors
      exhibited significant increases in a suite of traits including photosynthetic
      rate, respiration rate, leaf N, and stomatal conductance and a decrease in
      photosynthetic water-use efficiency. The lack of constitutive carbon costs
      associated with Cr4 resistance in non-stressed limber pine is consistent with a
      previous report that the R gene allele is not under selection in the absence of
      C. ribicola and suggests that host resistance may not bear a constitutive cost in
      pathosystems that have not coevolved. However, under challenge by C. ribicola,
      complete resistance to WPBR in limber pine has a significant cost to plant
      growth, though enhanced carbon acquisition post-infection may offset this
      somewhat. These costs and effects on performance further complicate predictions
      of this species' response in warmer future climates in the presence of WPBR.

PMID- 27706250
TI  - A New Giant Titanosauria (Dinosauria: Sauropoda) from the Late Cretaceous Bauru
      Group, Brazil.
AB  - Titanosaurian dinosaurs include some of the largest land-living animals that ever
      existed, and most were discovered in Cretaceous deposits of Argentina. Here we
      describe the first Brazilian gigantic titanosaur, Austroposeidon magnificus gen.
      et sp. nov., from the Late Cretaceous Presidente Prudente Formation (Bauru Group,
      Parana Basin), Sao Paulo State, southeast Brazil. The size of this animal is
      estimated around 25 meters. It consists of a partial vertebral column composed by
      the last two cervical and the first dorsal vertebrae, all fairly complete and
      incomplete portions of at least one sacral and seven dorsal elements. The new
      species displays four autapomorphies: robust and tall centropostzygapophyseal
      laminae (cpol) in the last cervical vertebrae; last cervical vertebra bearing the
      posterior centrodiapophyseal lamina (pcdl) bifurcated; first dorsal vertebra with
      the anterior and posterior centrodiapophyseal laminae (acdl/pcdl) curved
      ventrolaterally, and the diapophysis reaching the dorsal margin of the centrum;
      posterior dorsal vertebra bearing forked spinoprezygapophyseal laminae (sprl).
      The phylogenetic analysis presented here reveals that Austroposeidon magnificus
      is the sister group of the Lognkosauria. CT scans reveal some new osteological
      internal features in the cervical vertebrae such as the intercalation of dense
      growth rings with camellae, reported for the first time in sauropods. The new
      taxon further shows that giant titanosaurs were also present in Brazil during the
      Late Cretaceous and provides new information about the evolution and internal
      osteological structures in the vertebrae of the Titanosauria clade.

PMID- 27706251
TI  - Risk Factors for Non-Adherence to cART in Immigrants with HIV Living in the
      Netherlands: Results from the ROtterdam ADherence (ROAD) Project.
AB  - In the Netherlands, immigrant people living with HIV (PLWH) have poorer
      psychological and treatment outcomes than Dutch PLWH. This cross-sectional field
      study examined risk factors for non-adherence to combination Antiretroviral
      Therapy (cART) among immigrant PLWH. First and second generation immigrant PLWH
      attending outpatient clinics at two HIV-treatment centers in Rotterdam were
      selected for this study. Socio-demographic and clinical characteristics for all
      eligible participants were collected from an existing database. Trained
      interviewers subsequently completed questionnaires together with consenting
      participants (n = 352) to gather additional data on socio-demographic
      characteristics, psychosocial variables, and self-reported adherence to cART.
      Univariable and multivariable logistic regression analyses were conducted among
      301 participants who had used cART >=6 months prior to inclusion. Independent
      risk factors for self-reported non-adherence were (I) not having attended formal
      education or only primary school (OR = 3.25; 95% CI: 1.28-8.26, versus
      University), (II) experiencing low levels of social support (OR = 2.56; 95% CI:
      1.37-4.82), and (III) reporting low treatment adherence self-efficacy (OR = 2.99;
      95% CI: 1.59-5.64). Additionally, HIV-RNA >50 copies/ml and internalized HIV
      related stigma were marginally associated (P<0.10) with non-adherence (OR = 2.53;
      95% CI: 0.91-7.06 and OR = 1.82; 95% CI: 0.97-3.43). The findings that low
      educational attainment, lack of social support, and low treatment adherence self
      efficacy are associated with non-adherence point to the need for tailored
      supportive interventions. Establishing contact with peer immigrant PLWH who serve
      as role models might be a successful intervention for this specific population.

PMID- 27706252
TI  - Predictors of HIV Testing among Youth in Sub-Saharan Africa: A Cross-Sectional
      Study.
AB  - INTRODUCTION: In spite of a high prevalence of HIV infection among adolescents
      and young adults in sub-Saharan Africa, uptake of HIV testing and counseling
      among youth in the region remains sub-optimal. The objective of this study was to
      assess factors that influence uptake of HIV testing and counseling among youth
      aged 15-24 years in sub-Saharan Africa. METHODS: This study used the Demographic
      and Health Survey (DHS) data from countries that represent four geographic
      regions of sub-Saharan Africa: Congo (Brazzaville), representing central Africa
      (DHS 2011-2012); Mozambique, representing southern Africa (DHS 2011); Nigeria,
      representing western Africa (DHS 2013); and Uganda, representing eastern Africa
      (DHS 2011). Analyses were restricted to 23,367 male and female respondents aged
      15-24 years with complete data on the variables of interest. Chi-square tests and
      logistic regression models were used to assess predictors of HIV testing.
      Statistical significance was set at p< 0.01. RESULTS: The analysis revealed that
      a majority of the respondents were female (78.1%) and aged 20-24-years (60.7%).
      Only a limited proportion of respondents (36.5%) had ever tested for HIV and even
      fewer (25.7%) demonstrated comprehensive knowledge of HIV/AIDS. There was a
      significant association between HIV testing and respondents' gender, age, age at
      sexual debut, and comprehensive knowledge of HIV in the pooled sample. Older
      youth (adjusted OR (aOR) = 2.19; 99% CI = 1.99-2.40) and those with comprehensive
      knowledge of HIV (aOR = 1.98; 1.76-2.22) had significantly higher odds of ever
      being tested for HIV than younger respondents and those with limited HIV/AIDS
      knowledge respectively. Furthermore, men had lower odds of HIV testing than women
      (aOR = 0.32; 0.28-0.37). CONCLUSIONS: Reaching youth in sub-Saharan Africa for
      HIV testing continues to be a challenge. Public health programs that seek to
      increase HIV counseling and testing among youth should pay particular attention
      to efforts that target high-risk subpopulations of youth. The results further
      suggest that these initiatives would be strengthened by including strategies to
      increase HIV comprehensive knowledge.

PMID- 27706253
TI  - Morphological Characteristics of Electrophysiologically Characterized Layer Vb
      Pyramidal Cells in Rat Barrel Cortex.
AB  - Layer Vb pyramidal cells are the major output neurons of the neocortex and
      transmit the outcome of cortical columnar signal processing to distant target
      areas. At the same time they contribute to local tactile information processing
      by emitting recurrent axonal collaterals into the columnar microcircuitry. It is,
      however, not known how exactly the two types of pyramidal cells, called slender
      tufted and thick-tufted, contribute to the local circuitry. Here, we investigated
      in the rat barrel cortex the detailed quantitative morphology of biocytin-filled
      layer Vb pyramidal cells in vitro, which were characterized for their intrinsic
      electrophysiology with special emphasis on their action potential firing pattern.
      Since we stained the same slices for cytochrome oxidase, we could also perform
      layer- and column-related analyses. Our results suggest that in layer Vb the
      unambiguous action potential firing patterns "regular spiking (RS)" and
      "repetitive burst spiking (RB)" (previously called intrinsically burst spiking)
      correlate well with a distinct morphology. RS pyramidal cells are
      somatodendritically of the slender-tufted type and possess numerous local
      intralaminar and intracolumnar axonal collaterals, mostly reaching layer I. By
      contrast, their transcolumnar projections are less well developed. The RB
      pyramidal cells are somatodendritically of the thick-tufted type and show only
      relatively sparse local axonal collaterals, which are preferentially emitted as
      long horizontal or oblique infragranular collaterals. However, contrary to many
      previous slice studies, a substantial number of these neurons also showed axonal
      collaterals reaching layer I. Thus, electrophysiologically defined pyramidal
      cells of layer Vb show an input and output pattern which suggests RS cells to be
      more "locally segregating" signal processors whereas RB cells seem to act more on
      a "global integrative" scale.

PMID- 27706254
TI  - Novel Hydrophobin Fusion Tags for Plant-Produced Fusion Proteins.
AB  - Hydrophobin fusion technology has been applied in the expression of several
      recombinant proteins in plants. Until now, the technology has relied exclusively
      on the Trichoderma reesei hydrophobin HFBI. We screened eight novel hydrophobin
      tags, T. reesei HFBII, HFBIII, HFBIV, HFBV, HFBVI and Fusarium verticillioides
      derived HYD3, HYD4 and HYD5, for production of fusion proteins in plants and
      purification by two-phase separation. To study the properties of the
      hydrophobins, we used N-terminal and C-terminal GFP as a fusion partner.
      Transient expression of the hydrophobin fusions in Nicotiana benthamiana revealed
      large variability in accumulation levels, which was also reflected in formation
      of protein bodies. In two-phase separations, only HFBII and HFBIV were able to
      concentrate GFP into the surfactant phase from a plant extract. The separation
      efficiency of both tags was comparable to HFBI. When the accumulation was tested
      side by side, HFBII-GFP gave a better yield than HFBI-GFP, while the yield of
      HFBIV-GFP remained lower. Thus we present here two alternatives for HFBI as
      functional fusion tags for plant-based protein production and first step
      purification.

PMID- 27706255
TI  - The Effect of Albumin on MRP2 and BCRP in the Vesicular Transport Assay.
AB  - The ABC transporters multidrug resistance associated protein 2 (MRP2) and breast
      cancer resistance protein (BCRP) are of interest in drug development, since they
      affect the pharmacokinetics of several drugs. Membrane vesicle transport assays
      are widely used to study interactions with these proteins. Since albumin has been
      found to affect the kinetics of metabolic enzymes in similar membrane
      preparations, we investigated whether albumin affects the kinetic parameters of
      efflux transport. We found that albumin increased the Vmax of 5(6)-carboxy-2',7'
      dichlorofluorescein (CDCF) and estradiol-17-beta-D-glucuronide uptake into MRP2
      vesicles in the presence of 0.1% bovine serum albumin (BSA) by 2 and 1.5-fold,
      respectively, while BSA increased Lucifer yellow uptake by 30% in BCRP vesicles.
      Km values increased slightly, but the change was not statistically significant.
      The effect of BSA on substrate uptake was dependent on the vesicle amount, while
      increasing BSA concentration did not significantly improve substrate uptake.
      These results indicate a minor effect of albumin on MRP2 and BCRP, but it should
      be considered if albumin is added to transporter assays for example as a
      solubilizer, since the effect may be substrate or transporter specific.

PMID- 27706256
TI  - Time Series Analysis of Hemorrhagic Fever with Renal Syndrome: A Case Study in
      Jiaonan County, China.
AB  - Exact prediction of Hemorrhagic fever with renal syndrome (HFRS) epidemics must
      improve to establish effective preventive measures in China. A Seasonal
      Autoregressive Integrated Moving Average (SARIMA) model was applied to establish
      a highly predictive model of HFRS. Meteorological factors were considered
      external variables through a cross correlation analysis. Then, these factors were
      included in the SARIMA model to determine if they could improve the predictive
      ability of HFRS epidemics in the region. The optimal univariate SARIMA model was
      identified as (0,0,2)(1,1,1)12. The R2 of the prediction of HFRS cases from
      January 2014 to December 2014 was 0.857, and the Root mean square error (RMSE)
      was 2.708. However, the inclusion of meteorological variables as external
      regressors did not significantly improve the SARIMA model. This result is likely
      because seasonal variations in meteorological variables were included in the
      seasonal characteristics of the HFRS itself.

PMID- 27706257
TI  - The Relationship between Mating System and Genetic Diversity in Diploid Sexual
      Populations of Cyrtomium falcatum in Japan.
AB  - The impact of variation in mating system on genetic diversity is a well-debated
      topic in evolutionary biology. The diploid sexual race of Cyrtomium falcatum
      (Japanese holly fern) shows mating system variation, i.e., it displays two
      different types of sexual expression (gametangia formation) in gametophytes:
      mixed (M) type and separate (S) type. We examined whether there is variation in
      the selfing rate among populations of this species, and evaluated the
      relationship between mating system, genetic diversity and effective population
      size using microsatellites. In this study, we developed eight new microsatellite
      markers and evaluated genetic diversity and structure of seven populations (four
      M-type and three S-type). Past effective population sizes (Ne) were inferred
      using Approximate Bayesian computation (ABC). The values of fixation index (FIS),
      allelic richness (AR) and gene diversity (h) differed significantly between the M
      type (FIS: 0.626, AR: 1.999, h: 0.152) and the S-type (FIS: 0.208, AR: 2.718, h:
      0.367) populations (when admixed individuals were removed from two populations).
      Although evidence of past bottleneck events was detected in all populations by
      ABC, the current Ne of the M-type populations was about a third of that of the S
      type populations. These results suggest that the M-type populations have
      experienced more frequent bottlenecks, which could be related to their higher
      colonization ability via gametophytic selfing. Although high population
      differentiation among populations was detected (FST = 0.581, F'ST = 0.739), there
      was no clear genetic differentiation between the M- and S-types. Instead,
      significant isolation by distance was detected among all populations. These
      results suggest that mating system variation in this species is generated by the
      selection for single spore colonization during local extinction and
      recolonization events and there is no genetic structure due to mating system.

PMID- 27706258
TI  - HAG (Homoharringtonine, Cytarabine, G-CSF) Regimen for the Treatment of Acute
      Myeloid Leukemia and Myelodysplastic Syndrome: A Meta-Analysis with 2,314
      Participants.
AB  - BACKGROUND: In China, the combination of homoharringtonine, cytarabine, and G-CSF
      (HAG) has been extensively applied for treatment of acute myeloid leukemia (AML)
      and myelodysplastic syndrome (MDS). METHODS: We performed a meta-analysis of
      2,314 patients (AML, n = 1754; MDS, n = 560) to determine the overall safety and
      efficacy of this regimen. RESULTS: The complete response (CR) rate of AML
      patients (53%) was significantly higher than that of MDS/transformed-AML patients
      (45%; P = 0.007). The CR rate of patients with newly diagnosed AML (62%) was
      significantly higher than in patients with relapsed/refractory AML (50%; P =
      0.001). There were no significant difference in CR rates between elderly AML
      patients (54%) and all AML patients (P = 0.721). When compared with non-HAG
      regimens for AML/MDS induction therapy, the CR rate of patients treated with HAG
      was significantly higher than in treated with intensive chemotherapy (P = 0.000).
      No significant differences in CR rates were observed between patients treated
      with HAG and those treated with CAG (cytarabine, aclarubicin, G-CSF) regimens (P
      = 0.073). HAG regimen was well tolerated, with early death (ED) in 2%, grade IV
      myelosurrpression in 52% and infection in 50%. Reports of ED and rates of
      myelosuppression were reduced as compared with intensive chemotherapy (P = 0.000
      and P = 0.000, respectively). CONCLUSION: The HAG regimen is an effective and
      safe regimen for the treatment of AML and MDS, and appears to be more effective
      and better tolerated than intensive chemotherapy. Future randomized controlled
      trials and further meta-analyses are strongly needed to confirm its efficacy and
      safety, especially in comparison with intensive chemotherapy.

PMID- 27706259
TI  - Augmented Growth Hormone Secretion and Stat3 Phosphorylation in an Aryl
      Hydrocarbon Receptor Interacting Protein (AIP)-Disrupted Somatotroph Cell Line.
AB  - Aryl hydrocarbon receptor interacting protein (AIP) is thought to be a tumor
      suppressor gene, as indicated by a mutational analysis of pituitary somatotroph
      adenomas. However, the physiological significance of AIP inactivation in
      somatotroph cells remains unclear. Using CRISPR/Cas9, we identified a GH3 cell
      clone (termed GH3-FTY) in which Aip was genetically disrupted, and subsequently
      investigated its character with respect to growth hormone (Gh) synthesis and
      proliferation. Compared with GH3, GH3-FTY cells showed remarkably increased Gh
      production and a slight increase in cell proliferation. Gh-induced Stat3
      phosphorylation is known to be a mechanism of Gh oversecretion in GH3.
      Interestingly, phosphorylated-Stat3 expression in GH3-FTY cells was increased
      more compared with GH3 cells, suggesting a stronger drive for this mechanism in
      GH3-FTY. The phenotypes of GH3-FTY concerning Gh overproduction, cell
      proliferation, and increased Stat3 phosphorylation were significantly reversed by
      the exogenous expression of Aip. GH3-FTY cells were less sensitive to
      somatostatin than GH3 cells in the suppression of cell proliferation, which might
      be associated with the reduced expression of somatostatin receptor type 2. GH3
      FTY xenografts in BALB/c nude mice (GH3-FTY mice) formed more mitotic somatotroph
      tumors than GH3 xenografts (GH3 mice), as also evidenced by increased Ki67
      scores. GH3-FTY mice were also much larger and had significantly higher plasma Gh
      levels than GH3 mice. Furthermore, GH3-FTY mice showed relative insulin
      resistance compared with GH3 mice. In conclusion, we established a somatotroph
      cell line, GH3-FTY, which possessed prominent Gh secretion and mitotic features
      associated with the disruption of Aip.

PMID- 27706260
TI  - Comparison of Two Different Modes of Active Recovery on Muscles Performance after
      Fatiguing Exercise in Mountain Canoeist and Football Players.
AB  - BACKGROUND: The aim of this study is to assess if the application of different
      methods of active recovery (working the same or different muscle groups from
      those which were active during fatiguing exercise) results in significant
      differences in muscle performance and if the efficiency of the active recovery
      method is dependent upon the specific sport activity (training loads). DESIGN: A
      parallel group non-blinded trial with repeated measurements. METHODS: Thirteen
      mountain canoeists and twelve football players participated in this study.
      Measurements of the bioelectrical activity, torque, work and power of the vastus
      lateralis oblique, vastus medialis oblique, and rectus femoris muscles were
      performed during isokinetic tests at a velocity of 90 degrees /s. RESULTS: Active
      legs recovery in both groups was effective in reducing fatigue from evaluated
      muscles, where a significant decrease in fatigue index was observed. The muscles
      peak torque, work and power parameters did not change significantly after both
      modes of active recovery, but in both groups significant decrease was seen after
      passive recovery. CONCLUSIONS: We suggest that 20 minutes of post-exercise active
      recovery involving the same muscles that were active during the fatiguing
      exercise is more effective in fatigue recovery than active exercise using the
      muscles that were not involved in the exercise. Active arm exercises were less
      effective in both groups which indicates a lack of a relationship between the
      different training regimens and the part of the body which is principally used
      during training.

PMID- 27706262
TI  - The 300 Most-Cited Articles in Implant Dentistry.
AB  - PURPOSE: The purpose of this study was to review and evaluate the characteristics
      of the 300 most-cited articles that have been published in the most important
      implant dentistry journals. MATERIALS AND METHODS: A search and selection of the
      most-cited articles up to October 2014 was conducted for implant journals with
      the highest impact factors, according to the ISI Web of Science. The 300-most
      cited articles were evaluated according to the most commonly studied topics and
      methodological designs used. The most-cited journals and the number of articles
      cited by year were calculated. Descriptive statistics were used to summarize the
      results. RESULTS: The most-cited topics consisted of implant success/survival and
      guided bone regeneration, and the most-cited methodological designs were case
      series and cohort studies. The most frequently referenced journal was The
      International Journal of Oral and Maxillofacial Implants, with 47% of the
      citations, and the period with the most citations was 1996 to 2000. CONCLUSION:
      Longitudinal studies of success and survival have had great scientific impact on
      the practice of implant dentistry. Awareness of the most-cited articles in
      implant dentistry will contribute to scientific advances, as it serves to
      identify the most researched areas, the most frequently used study designs, and
      areas that require further research.

PMID- 27706261
TI  - Homogeneous Inflammatory Gene Profiles Induced in Human Dermal Fibroblasts in
      Response to the Three Main Species of Borrelia burgdorferi sensu lato.
AB  - In Lyme borreliosis, the skin is the key site for bacterial inoculation by the
      infected tick and for cutaneous manifestations. We previously showed that
      different strains of Borrelia burgdorferi sensu stricto isolated from tick and
      from different clinical stages of the Lyme borreliosis (erythema migrans, and
      acrodermatitis chronica atrophicans) elicited a very similar transcriptional
      response in normal human dermal fibroblasts. In this study, using whole
      transcriptome microarray chips, we aimed to compare the transcriptional response
      of normal human dermal fibroblasts stimulated by 3 Borrelia burgdorferi sensu
      lato strains belonging to 3 main pathogenic species (B. afzelii, B. garinii and
      B. burgdorferi sensu stricto) in order to determine whether "species-related"
      inflammatory pathways could be identified. The three Borrelia strains tested
      exhibited similar transcriptional profiles, and no species-specific fingerprint
      of transcriptional changes in fibroblasts was observed. Conversely, a common core
      of chemokines/cytokines (CCL2, CXCL1, CXCL2, CXCL6, CXCL10, IL-6, IL-8) and
      interferon-related genes was stimulated by all the 3 strains. Dermal fibroblasts
      appear to play a key role in the cutaneous infection with Borrelia, inducing a
      homogeneous inflammatory response, whichever Borrelia species was involved.

PMID- 27706264
TI  - Three-Dimensional Accuracy of Digital Implant Impressions: Effects of Different
      Scanners and Implant Level.
AB  - PURPOSE: To compare the three-dimensional (3D) accuracy of conventional direct
      implant impressions with digital implant impressions from three intraoral
      scanners, as well as different implant levels-bone level (BL) and tissue level
      (TL). MATERIALS AND METHODS: Two-implant master models were used to simulate a
      threeunit implant-supported fixed dental prosthesis. Conventional test models
      were made with direct impression copings and polyether impressions. Scan bodies
      were hand-tightened onto master models and scanned with the three scanners. This
      was done for the TL and BL test groups, for a total of eight test groups (n = 5
      each). A coordinate measuring machine measured linear distortions (dx, dy, dz),
      global linear distortion (dR), angular distortions (dthetay, dthetax), and
      absolute angular distortions (Absdthetay, Absdthetax) between the master models,
      test models, and .stl files of the digital scans. RESULTS: The mean dR ranged
      from 35 to 66 MUm; mean dthetay angular distortions ranged from -0.186 to 0.315
      degrees; and mean dthetax angular distortions ranged from -0.206 to 0.164
      degrees. Two-way analysis of variance showed that the impression type had a
      significant effect on dx, dz, and Absdthetay, and the implant level had a
      significant effect on dx and Absdthetax (P < .05). Among the BL groups, the mean
      dR of the conventional group was lower than and significantly different from the
      digital test groups (P = .010), while among the TL groups, there was no
      statistically significant difference (P = .572). CONCLUSION: The 3D accuracy of
      implant impressions varied according to the impression technique and implant
      level. For BL test groups, the conventional impression group had significantly
      lower distortion than the digital impression groups. Among the digital test
      groups, the TR system had comparable mean linear and absolute angular distortions
      to the other two systems but exhibited the smallest standard deviations.

PMID- 27706263
TI  - Gene-Activated Titanium Surfaces Promote In Vitro Osteogenesis.
AB  - PURPOSE: Commercially pure titanium (CpTi) and its alloys possess favorable
      mechanical and biologic properties for use as implants in orthopedics and
      dentistry. However, failures in osseointegration still exist and are common in
      select individuals with risk factors such as smoking. Therefore, in this study, a
      proposal was made to enhance the potential for osseointegration of CpTi discs by
      coating their surfaces with nanoplexes comprising polyethylenimine (PEI) and
      plasmid DNA (pDNA) encoding bone morphogenetic protein-2 (pBMP-2). MATERIALS AND
      METHODS: The nanoplexes were characterized for size and surface charge with a
      range of N/P ratios (the molar ratio of amine groups of PEI to phosphate groups
      in pDNA backbone). CpTi discs were surface characterized for morphology and
      composition before and after nanoplex coating using scanning electron microscopy
      (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and
      X-ray powder diffraction (XRD). The cytotoxicity and transfection ability of CpTi
      discs coated with nanoplexes of varying N/P ratios in human bone marrow-derived
      mesenchymal stem cells (BMSCs) was measured via MTS assays and flow cytometry,
      respectively. RESULTS: The CpTi discs coated with nanoplexes prepared at an N/P
      ratio of 10 (N/P-10) were considered optimal, resulting in 75% cell viability and
      14% transfection efficiency. Enzyme-linked immunosorbent assay results
      demonstrated a significant enhancement in BMP-2 protein secretion by BMSCs 7 days
      posttreatment with PEI/pBMP-2 nanoplexes (N/P-10) compared to the controls, and
      real-time PCR data demonstrated that the BMSCs treated with PEI/pBMP-2 nanoplex
      coated CpTi discs resulted in an enhancement of Runx-2, alkaline phosphatase, and
      osteocalcin gene expressions on day 7 posttreatment. In addition, these BMSCs
      demonstrated enhanced calcium deposition on day 30 posttreatment as determined by
      qualitative (alizarin red staining) and quantitative (atomic absorption
      spectroscopy) assays. CONCLUSION: It can be concluded that PEI/pBMP-2 nanoplex
      (N/P-10)-coated CpTi discs have the potential to induce osteogenesis and enhance
      osseointegration.

PMID- 27706265
TI  - Precision Fit of Screw-Retained Implant-Supported Fixed Dental Prostheses
      Fabricated by CAD/CAM, Copy-Milling, and Conventional Methods.
AB  - PURPOSE: The aim of this study was to evaluate the effectiveness of fabrication
      methods (computer-aided design/computer-aided manufacture [CAD/CAM], copy
      milling, and conventional casting) in the fit accuracy of three-unit, screw
      retained fixed dental prostheses. MATERIALS AND METHODS: Sixteen three-unit
      implant-supported screw-retained frameworks were fabricated to fit an in vitro
      model. Eight frameworks were fabricated using the CAD/CAM system, four in
      zirconia and four in cobalt-chromium. Four zirconia frameworks were fabricated
      using the copy-milled system, and four were cast in cobalt-chromium using
      conventional casting with premachined abutments. The vertical and horizontal
      misfit at the implant-framework interface was measured using scanning electron
      microscopy at *250. The results for vertical misfit were analyzed using Kruskal
      Wallis and Mann-Whitney tests. The horizontal misfits were categorized as
      underextended, equally extended, or overextended. Statistical analysis
      established differences between groups according to the chi-square test (alpha =
      .05). RESULTS: The mean vertical misfit was 5.9 +/- 3.6 MUm for CAD/CAM
      fabricated zirconia, 1.2 +/- 2.2 MUm for CAD/CAM-fabricated cobalt-chromium
      frameworks, 7.6 +/- 9.2 MUm for copy-milling-fabricated zirconia frameworks, and
      11.8 (9.8) MUm for conventionally fabricated frameworks. The Mann-Whitney test
      revealed significant differences between all but the zirconia-fabricated
      frameworks. A significant association was observed between the horizontal misfits
      and the fabrication method. The percentage of horizontal misfits that were
      underextended and overextended was higher in milled zirconia (83.3%), CAD/CAM
      cobaltchromium (66.7%), cast cobalt-chromium (58.3%), and CAD/CAM zirconia
      (33.3%) frameworks. CONCLUSION: CAD/CAM-fabricated frameworks exhibit better
      vertical misfit and low variability compared with copy-milled and conventionally
      fabricated frameworks. The percentage of interfaces equally extended was higher
      when CAD/CAM and zirconia were used.

PMID- 27706266
TI  - Intermittent Parathyroid Hormone Improves Bone Formation Around Titanium Implants
      in Osteoporotic Rat Maxillae.
AB  - PURPOSE: Parathyroid hormone (PTH) plays an important role in the treatment of
      osteoporosis due to its anabolic effect. In this study, PTH was administered
      intermittently to rats with ovariectomy-induced osteoporosis, titanium implants
      were placed into the rat maxillae, and the response of surrounding bone was
      evaluated. MATERIALS AND METHODS: A total of 30 female 8-week-old Sprague-Dawley
      rats were either ovariectomized to induce osteoporosis or sham operated. After 8
      weeks, the upper right first molar was extracted and after a 4-week healing
      period an implant was placed. The animals were then divided into three groups:
      the PTH group (n = 10), which had been ovariectomized and received postimplant
      PTH; the OVX group (n = 10), which had been ovariectomized but did not receive
      postimplant PTH; and the control group (n = 10), which had been sham operated
      only (n = 10). Following implant placement, the rats in the PTH group received
      intermittent doses (three times a week) of PTH (30 MUg/kg) subcutaneously in the
      dorsum. All the rats were sacrificed 4 weeks after implantation and specimens of
      the peri-implant maxillary bone were harvested, including the implant. Samples
      were evaluated by histomorphometric analysis and three-dimensional microcomputed
      tomography. RESULTS: Histomorphometric results showed that the mean bone area per
      tissue area (BA/TA) was 54.16% +/- 2.2% in the PTH group and 45.24% +/- 6.3% in
      the OVX group. The percentage of bone-to-implant contact (BIC) was 45.58% +/-
      9.4% in the PTH group and 32.00% +/- 10.9% in the OVX group. Mean BA/TA and mean
      BIC values in the PTH group were higher than those in the OVX group; however, the
      differences were not statistically significant (P > .05). Microstructural data
      also showed differences between the groups. Bone volume was greater and
      trabecular bone was thicker in the PTH group than in the OVX group and more
      trabeculae were found in the PTH group. Bone mineral density was also higher in
      the PTH group. However, statistical analysis failed to show a significant
      difference between these two groups in any parameters other than trabecular
      thickness (P = .023). CONCLUSION: Despite the limitations of this study,
      intermittent PTH administration in humans may be helpful in accelerating new bone
      formation around implants. PTH treatment could improve clinical outcomes when
      dental implants are placed in jaws with low-quality bone.

PMID- 27706267
TI  - Changes in Lip Profile of Edentulous Patients After Placement of Maxillary
      Implant-Supported Fixed Prosthesis: Is a Wax Try-in a Reliable Diagnostic Tool?
AB  - PURPOSE: A diagnostic wax try-in has been recommended to correctly design the
      future prosthesis for edentulous maxillae and to predict its effect on the
      supporting oral tissues. The objectives of this study were to analyze (1) the
      reliability of this diagnostic tool in planning fixed implant-supported
      prostheses and (2) the amount of prosthetic compensation required. MATERIALS AND
      METHODS: Nine female patients participated in this prospective study (mean age,
      53.6 years). After anamnesis, clinical examination, and preoperative analysis,
      the patients underwent preoperative prosthetic preparation, and the wax try-in
      was fabricated. To evaluate the efficiency of the diagnostic wax try-in, three
      profile cephalograms were taken of each patient: (1) with the initial
      conventional prosthesis, (2) with the wax try-in, and (3) with the implant
      supported prosthesis. Two analyses were carried out for the assessment of lip
      support: the nasolabial angle and Steiner's S-line. To analyze the amount of
      prosthetic compensation, two measurements-vertical and horizontal distances- were
      obtained for each wax try-in and final prosthesis. RESULTS: For the Steiner's S
      line, the results of the statistical tests indicated no significant difference
      between the initial and final prosthesis for the upper (P = .237) and lower lips
      (P = .237), and between the wax try-in and final prosthesis for the upper (P =
      .463) and lower lips (P = .463). Regarding the nasolabial angle, the results of
      the statistical tests indicated no significant difference between the initial and
      final prosthesis (P = .594), and between the wax try-in and final prosthesis (P =
      .800). Regarding prosthetic compensation, the results of the statistical test
      indicated no significant difference between the vertical (P = .753) and
      horizontal evaluations (P = .855) carried out for the wax try-in and those for
      the final prosthesis. CONCLUSION: On the basis of the data collected, it was
      concluded that the methods of replacing muco-supported prostheses with implant
      supported fixed prostheses were efficient at maintaining the original lip design.
      The wax try-in was capable of predicting the future lip design and the prosthetic
      compensation of the final prosthesis. More studies are required to consolidate
      these data.

PMID- 27706268
TI  - The Not-So-Near Death of Autopsies in the U.S.

PMID- 27706269
TI  - Changes in the Maintenance of Certification (MOC) process have not gone far
      enough.

PMID- 27706270
TI  - Medical Decision-Making for Unrepresented Patients.

PMID- 27706271
TI  - The Rio 2016 Polyclinic - An Athlete-Centered Experience in the Olympic Village.

PMID- 27706272
TI  - Collaboration and Collegiality: The Fuel For Growth in Sports Medicine.

PMID- 27706273
TI  - Preparticipation Physical Exams: The Rhode Island Perspective, A Call for
      Standardization.
AB  - As of 2015, 98% of U.S. states require preparticipation exams (PPE) before
      participating in scholastic sports. Despite widespread availability of a PPE
      monograph endorsed by six medical societies, a lack of uniformity exists
      regarding implementation of the PPE among Rhode Island health care providers
      (HCPs). Consequently, significant variability exists regarding how comprehensive
      a history and physical exam screening is conducted for adolescent athletes
      looking for sports participation clearance. The purpose of this document is to:
      1) establish a uniform screening process in Rhode Island for the PPE utilizing a
      peer-reviewed history and physical exam; 2) familiarize HCPs with the 2010 PPE
      monograph, with emphasis on the cardiovascular and musculoskeletal (MSK) systems;
      3) encourage HCPs to treat the PPE as a separate entity from the annual wellness
      visit; 4) engage HCPs and sports medicine providers in Rhode Island to improve
      the quality and process of evaluating adolescent athletes for sports
      participation. [Full article available at http://rimed.org/rimedicaljournal-2016
      10.asp].

PMID- 27706274
TI  - Current Concepts in Sports-related Concussion.
AB  - Increasing concern over the acute and long-term consequences of sports-related
      concussion has generated widespread interest and attention. This article provides
      an overview of concussion in athletes, including diagnostic and management
      considerations, and highlights the clinical challenges associated with repeated
      minor head trauma in sports. [Full article available at
      http://rimed.org/rimedicaljournal-2016-10.asp].

PMID- 27706275
TI  - Diagnosis and Management of Meniscal Injury.
AB  - Meniscal injury is a common cause for presentation to the emergency department or
      primary care physician's office. Meniscal injuries can be the result of a
      forceful, twisting event in a young athlete's knee or it can insidiously present
      in the older patient. Many patients with meniscal pathology appropriately undergo
      conservative management with a primary care physician while some may need
      referral to an orthopedist for operative intervention. Arthroscopic surgery to
      address the menisci is the most frequently performed procedure on the knee and
      one of the most regularly performed surgeries in orthopedic surgery.1 The purpose
      of this paper is to help elucidate the diagnosis and management of meniscal
      pathology resulting in knee pain. [Full article available at
      http://rimed.org/rimedicaljournal-2016-10.asp].

PMID- 27706276
TI  - Understanding Athletic Pubalgia: A Review.
AB  - Athletic Pubalgia, more commonly known as sports hernia, is defined as chronic
      lower abdominal and groin pain without the presence of a true hernia. It is
      increasingly recognized in athletes as a source of groin pain and is often
      associated with other pathology. A comprehensive approach to the physical exam
      and a strong understanding of hip and pelvic anatomy are critical in making the
      appropriate diagnosis. Various management options are available. We review the
      basic anatomy, patholophysiology, diagnostic approach and treatment of athletic
      pubalgia as well as discuss associated conditions such as femoroacetabular
      impingement. [Full article available at http://rimed.org/rimedicaljournal-2016
      10.asp].

PMID- 27706277
TI  - The Decline of the Autopsy in Rhode Island and Nationwide: Past Trends and Future
      Directions.
AB  - The autopsy has long been a fundamental aspect of medical practice and research.
      However, in the last 50 years, the proportion of deaths for which an autopsy is
      performed has decreased dramatically. Here we examine some of the reasons for the
      decline of the autopsy, as well as several interventions that have been proposed
      to revive it. We also present autopsy utilization data from the Lifespan system,
      which mirrors nationwide trends. [Full article available at
      http://rimed.org/rimedicaljournal-2016-10.asp].

PMID- 27706278
TI  - Fluid Choice Matters in Critically-ill Patients with Acute Pancreatitis: Lactated
      Ringer's vs. Isotonic Saline.
AB  - OBJECTIVES: To investigate the effect of different crystal- loid solutions on
      clinical outcomes in critically-ill patients with acute pancreatitis (AP).
      METHODS: We conducted a retrospective study of patients with AP admitted to the
      ICU using the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC
      III) database. We investigated the effect of fluid type; lactated ringer's (LR)
      vs. isotonic saline (IS) on hospital mortality rates, and ICU length of stay
      (LOS). RESULTS: Hospital mortality of the 198 included patients was 12%. For
      fluid type, 32.9% were resuscitated with LR vs. 67.1% with IS. Hospital mortality
      was lower in the LR group (5.8%) vs. 14.9% for IS group, odds ratio of 3.10
      [P=0.041]. This effect was still observed after adjusting for confounders.
      However, ICU LOS was longer in LR compared to IS group; 6.2+/-6.9 vs. 4.2+/-4.49
      days respectively [P= 0.020]. CONCLUSION: The type of fluid used for
      resuscitation in AP may affect the outcome. LR may have survival benefit over IS
      in critically-ill patients with AP. [Full article available at
      http://rimed.org/rimedicaljournal-2016-10.asp].

PMID- 27706279
TI  - A Five-Year Evolution of a Student-led Elective on Health Disparities at The
      Alpert Medical School.
AB  - BACKGROUND AND OBJECTIVE: Medical students are often unprepared for social
      challenges in caring for safety net patients. We aim to evaluate and chronicle
      the evolution of a pre-clinical elective alongside medical disparities
      curriculum. DESIGN AND METHODS: Medical students designed the course to
      supplement clinical training on care of vulnerable patients. From 2011-2015,
      there have been 80 first-year medical student participants, five cohorts of
      second-year course leaders, and two supporting faculty advisors for this 10-12
      session evening elective. RESULTS: Students (n=67) rated the course extremely
      highly (ranging from 4.4-4.6 on a five-point Likert scale). Medical students
      reported having significantly more knowledge of underserved populations after
      taking the course (difference=0.72, SE=0.16, P <0.001). Career interests and
      attitudes toward health disparities remained strong after taking the course.
      CONCLUSIONS: This student-created elective equipped participants with improved
      knowledge in caring for underserved patients and contributed to the incorporation
      of health disparities in medical curriculum. [Full article available at
      http://rimed.org/rimedicaljournal-2016-10.asp].

PMID- 27706280
TI  - Medical School Ranking and Student Research Opportunities.
AB  - OBJECTIVE: This study aimed to characterize the current state of student research
      opportunities in a sample of US medical schools ranked in three different tiers.
      METHODS: The authors examined the websites for five US medical schools in each of
      the first, second, and third tiers per National Institutes of Health funding and
      U.S. News & World Report rankings. Available research opportunities were
      identified and categorized. RESULTS: There were 26 schools in the first (n=6),
      second (n=10), and third (n=10) tiers. From the first, second, and third tiers,
      4/6 (67%), 1/10 (10%) and none, respectively, required a research experience
      (p=0.003); 6/6 (100%), 4/10 (40%) and 1/10 (10%), respectively, offered
      internally funded one-year research (p=0.002); and 5/6 (83%), 4/10 (40%) and 2/10
      (20%), respectively, offered student research days (p=0.045). CONCLUSIONS: Higher
      ranked schools provided more opportunities for student research by providing
      internally funded one-year research, requiring research, and offering student
      research days. [Full article available at http://rimed.org/rimedicaljournal-2016
      10.asp].

PMID- 27706281
TI  - Systemic Amyloidosis Masquerading as Intractable Cardiomyopathy.

PMID- 27706294
TI  - Medical Signal Processing and Biomedical Imaging.

PMID- 27706295
TI  - The Health Record - why is it so hard?

PMID- 27706282
TI  - Community Health Teams: A Healthcare Provider's System Transformation
      Opportunity.
AB  - "The goal of community health teams is to develop and implement care models that
      integrate clinical and community health promotion and preventive services for
      patients." -Association of State and Territorial Health Officials (ASTHO)1 Eleven
      community health teams (CHTs) operate in various geographies within Rhode Island.
      Physicians and payers refer their highest-risk patients to CHTs that serve as
      community extenders. Community health workers and others work to link referred
      individuals to primary care and work to address the other determinants affecting
      their health, such as safe housing. Since much of health is driven by factors
      outside of the healthcare setting, CHTs compliment the work of physicians within
      the office environment. Transforming practices and addressing both the physical
      and behavioral needs of patients simultaneously is key to CHT success. This
      article attempts to quantify the expanding need for CHTs within Rhode Island and
      describes ways in which CHTs as a practice transformation resource may be
      leveraged by providers. [Full article available at
      http://rimed.org/rimedicaljournal-2016-10.asp].

PMID- 27706296
TI  - Ubiquitous Health Care Systems: A New Paradigm for Medical Informatics?

PMID- 27706297
TI  - Education and Consumer Informatics - patient involvement and health outcomes.

PMID- 27706299
TI  - The Full Spectrum of Biomedical Informatics Research and Education at OHSU.

PMID- 27706298
TI  - Health Information Systems.

PMID- 27706300
TI  - Decision Support, Knowledge Representation and Management.

PMID- 27706301
TI  - Achievements after Six Years of The International Partnership for Health
      Informatics Education.

PMID- 27706302
TI  - E-Health Strategies Worldwide.

PMID- 27706303
TI  - Health and Clinical Management.

PMID- 27706305
TI  - New e-Health Tracks in Engineering Education of the Politecnico di Milano.

PMID- 27706304
TI  - Health and Medical Informatics Education in Japan.

PMID- 27706306
TI  - A review of Primary Care Informatics: past progress, present reality, future
      prospects.

PMID- 27706307
TI  - The Agenda of Wearable Healthcare.

PMID- 27706308
TI  - Health Informatics Masters Education, Online Learning and Student Support.

PMID- 27706309
TI  - Bioinformatics and Systems Biology - towards Integrative Biology.

PMID- 27706310
TI  - Biomedical Informatics Training Program at Vanderbilt University.

PMID- 27706311
TI  - Towards Clinical Bioinformatics.

PMID- 27706312
TI  - Trends in Health Care Education: Research Opportunities in Teaching and Learning.

PMID- 27706313
TI  - Teaching probabilistic medical reasoning with the Elvira software.

PMID- 27706314
TI  - Advances in Medical Signal Processing.

PMID- 27706315
TI  - Curated databases and their role in clinical bioinformatics.

PMID- 27706316
TI  - Decision Support, Knowledge Representation and Management.

PMID- 27706317
TI  - New Challenges for Health Informatics.

PMID- 27706318
TI  - Public Health Implications of Bioinformatics.

PMID- 27706319
TI  - Training in Health Informatics in Brazil.

PMID- 27706320
TI  - Medical Informatics Education in Bosnia and Herzegovina.

PMID- 27706322
TI  - Biomedical Imaging.

PMID- 27706321
TI  - Health and Clinical Management.

PMID- 27706323
TI  - The Quest for Identity of Health Informatics and for Guidance to Education in it 
      The German Reisensburg Conference of 1973 Revisited.

PMID- 27706324
TI  - Structuring the Medical Narrative in Patient Records - A Further Step Towards a
      Multi- Accessible EHR.

PMID- 27706325
TI  - Knowledge Management In Health Care Organizations.

PMID- 27706326
TI  - Towards Clinical Bioinformatics.

PMID- 27706327
TI  - Towards Clinical Bioinformatics.

PMID- 27706328
TI  - Health Information Management Education at the Institute of Health Policy and
      Management of the Erasmus University Medical Center.

PMID- 27706329
TI  - Health Information Systems.

PMID- 27706331
TI  - Quality of Healthcare: The Role of Informatics.

PMID- 27706330
TI  - Leveraging IT to Improve Patient Safety.

PMID- 27706332
TI  - Virtual Rehabilitation - Benefits and Challenges.

PMID- 27706333
TI  - Computer-Supported Education.

PMID- 27706334
TI  - A 2'200-bed laboratory: research and education in medical informatics at Geneva
      University Hospitals.

PMID- 27706335
TI  - Medical Image Processing: New Perspectives in Computer Supported Diagnostics,
      Computer Aided Surgery and Medical Education and Training.

PMID- 27706336
TI  - Quality of health care: informatics foundations.

PMID- 27706337
TI  - Research and education directions in Medical Informatics at the Aristotle
      University of Thessaloniki.

PMID- 27706338
TI  - Informatics Research, Development, and Training at the Lister Hill National
      Center for Biomedical Communications.

PMID- 27706339
TI  - Challenges in Medical Informatics. A Discipline Coming of Age.

PMID- 27706340
TI  - Medical Applications of Virtual Environments.

PMID- 27706341
TI  - Knowledge-Based Systems: Enhancing the Quality of Care.

PMID- 27706342
TI  - Introduction to the Department of Medical Information Science of Osaka University
      Hospital.

PMID- 27706343
TI  - Computational approach towards challenges in the post-genomic era.

PMID- 27706344
TI  - Biomedical Signal Processing.

PMID- 27706345
TI  - The changing scenery of patient records.

PMID- 27706346
TI  - Health and Clinical Management.

PMID- 27706347
TI  - Quality health care requires quality patient data.

PMID- 27706348
TI  - Quality of Health Care: The Role of Informatics.

PMID- 27706350
TI  - Imaging Informatics and the Human Brain Project: the Role of Structure.

PMID- 27706349
TI  - Visible Human Project: From Data to Knowledge.

PMID- 27706351
TI  - Information Retrieval and Health/Clinical Management.

PMID- 27706352
TI  - Knowledge Processing and Decision Support Systems.

PMID- 27706353
TI  - Educational technology as a scientific discipline.

PMID- 27706355
TI  - Bioinformatics.

PMID- 27706354
TI  - Education and Research in Health Informatics at the Faculty of Medicine of
      Marseille, Laboratory for Education and Research in Medical Information
      Processing (LERTIM).

PMID- 27706356
TI  - Some Evaluations of Informatics Applications in Health Care.

PMID- 27706357
TI  - People, Organizational, and Social Issues: Evaluation as an exemplar.

PMID- 27706358
TI  - What can we currently expect from patient records?

PMID- 27706360
TI  - Education in medical informatics on the basis of the information technology
      curriculum at the Veszprem University.

PMID- 27706359
TI  - Standardization of health informatics - results and challenges.

PMID- 27706361
TI  - Signal Processing.

PMID- 27706362
TI  - The Evolving Biomedical Informatics Programs in Taipei Medical University.

PMID- 27706363
TI  - Inaugural Address.

PMID- 27706364
TI  - Education Downunder (Centre of Medical Informatics, Monash University).

PMID- 27706365
TI  - Challenges for Medical Informatics as an Academic Discipline: Workshop Report.

PMID- 27706366
TI  - Model-enhanced neuroimaging: clinical, research, and educational applications.

PMID- 27706367
TI  - Medical Informatics Training and Research at Columbia University.

PMID- 27706368
TI  - From Digital Anatomy to Virtual Scalpels and Image Guided Therapy.

PMID- 27706369
TI  - Medical Imaging Informatics.

PMID- 27706370
TI  - Diversity and evolution of plant diacylglycerol acyltransferase (DGATs) unveiled
      by phylogenetic, gene structure and expression analyses.
AB  - Since the first diacylglycerol acyltransferase (DGAT) gene was characterized in
      plants, a number of studies have focused on understanding the role of DGAT
      activity in plant triacylglycerol (TAG) biosynthesis. DGAT enzyme is essential in
      controlling TAGs synthesis and is encoded by different genes. DGAT1 and DGAT2 are
      the two major types of DGATs and have been well characterized in many plants. On
      the other hand, the DGAT3 and WS/DGAT have received less attention. In this
      study, we present the first general view of the presence of putative DGAT3 and
      WS/DGAT in several plant species and report on the diversity and evolution of
      these genes and its relationships with the two main DGAT genes (DGAT1 and DGAT2).
      According to our analyses DGAT1, DGAT2, DGAT3 and WS/DGAT are very divergent
      genes and may have distinct origin in plants. They also present divergent
      expression patterns in different organs and tissues. The maintenance of several
      types of genes encoding DGAT enzymes in plants demonstrates the importance of
      DGAT activity for TAG biosynthesis. Evolutionary history studies of DGATs coupled
      with their expression patterns help us to decipher their functional role in
      plants, helping to drive future biotechnological studies.

PMID- 27706371
TI  - The effects of old and recent migration waves in the distribution of HBB*S globin
      gene haplotypes.
AB  - Sickle cell hemoglobin is the result of a mutation at the sixth amino acid
      position of the beta (beta) globin chain. The HBB*S gene is in linkage
      disequilibrium with five main haplotypes in the beta-globin-like gene cluster
      named according to their ethnic and geographic origins: Bantu (CAR), Benin (BEN),
      Senegal (SEN), Cameroon (CAM) and Arabian-Indian (ARAB). These haplotypes
      demonstrated that the sickle cell mutation arose independently at least five
      times in human history. The distribution of betaS haplotypes among Brazilian
      populations showed a predominance of the CAR haplotype. American populations were
      clustered in two groups defined by CAR or BEN haplotype frequencies. This
      scenario is compatible with historical records about the slave trade in the
      Americas. When all world populations where the sickle cell gene occurs were
      analyzed, three clusters were disclosed based on CAR, BEN or ARAB haplotype
      predominance. These patterns may change in the next decades due to recent
      migrations waves. Since these haplotypes show different clinical characteristics,
      these recent migrations events raise the necessity to develop optimized public
      health programs for sickle cell disease screening and management.

PMID- 27706372
TI  - Cessation of dangerousness status: an analysis of 224 reports from the Instituto
      de Pericias Heitor Carrilho, Rio de Janeiro, Brazil.
AB  - Objectives:: To evaluate factors related to dangerousness cessation at the end of
      involuntary commitment based on an analysis of expert reports. In light of the
      current legal requirement of dangerousness cessation as a pre-requisite for
      prison or internment release of individuals subjected to the safety measure, we
      sought elements to reflect on the practice of expert examiners in charge of
      making this decision. Methods:: The authors revised 224 expert psychiatric
      dangerousness cessation reports released 2011 through 2014 and collected data for
      a statistical analysis. Results:: The following variables were associated with
      positive risk cessation assessments: no inadequate behavior (according to the
      assistant professionals), no productive psychotic symptoms, no negative symptoms,
      presence of insight, presence of a support network, and no psychoactive substance
      abuse. The following variables were associated with negative dangerousness
      cessation decisions: early onset of malfunction, lack of insight, negative
      attitudes, active signs of major mental illness, presence of impulsiveness, poor
      response to treatment, presence of plans lacking feasibility, exposure to
      destabilizing factors, lack of personal support, and presence of stress.
      Conclusions:: In this study we were able to identify factors associated with
      dangerousness in a sample of expert reports. The knowledge of factors linked to a
      higher risk of recidivism in illegal activities or violent behavior is crucial
      for decision-making regarding the release of offenders after their legally
      established period of involuntary commitment.

PMID- 27706373
TI  - Victimization, perception of insecurity, and changes in daily routines in Mexico.
AB  - OBJECTIVE: To analyze the relationships between victimization, perception of
      insecurity, and changes in routines. METHODS: The 8,170 subjects of both sexes
      (49.9% women and 50.1% men) aged between 12 and 60 years, selected from a
      proportional stratified sampling, participated in this study. The measuring
      instrument was an adaptation of the National Survey on Victimization and
      Perception of Public Security. Chi-square tests were performed. RESULTS: The
      results show significant differences on victimization and sex regarding
      perception of insecurity, restrictions on everyday activities, and protection
      measures. 13.1% of those interviewed claimed to have been victims of a crime in
      the past 12 months. 52.7% of women considered their municipality as unsafe or
      very unsafe. In the case of men, this percentage was 58.2%. Female victims
      reported significant restrictions in everyday activities when compared to non
      victims. In relation to men, the percentage of victims with a high restriction of
      activities was higher in male victims than non-victims. In the group of
      victimized women, the segment of women who opted for increased measures of
      protection against crime was larger than expected, while those of non-victims who
      took less protective measures was lower than expected. These same results were
      observed in the group of men. CONCLUSIONS: The experience of victimization
      implies a greater perception of insecurity. However, the climate of insecurity is
      widespread in a large number of citizens. Gender differences in a high-crime
      environment show the importance of investigating in depth the roles of both
      genders in the perception of insecurity and changes in routines. OBJETIVO:
      Analizar las relaciones existentes entre victimizacion, percepcion de inseguridad
      y cambios en las rutinas. METODOS: Participaron en este estudio 8,170 sujetos de
      ambos sexos (49.9% mujeres y 50.1% hombres) de entre 12 y 60 anos, seleccionados
      a partir de un muestro estratificado proporcional. El instrumento de medida fue
      una adaptacion de la Encuesta Nacional de Victimizacion y Seguridad Publica. Se
      realizaron pruebas Chi-cuadrado. RESULTADOS: Los resultados evidencian
      diferencias significativas en cuanto a victimizacion y sexo con respecto a
      percepcion de inseguridad, restricciones de actividades cotidianas y medidas de
      proteccion. Un 13.1% de las personas entrevistadas afirmaron haber sido victimas
      de un delito en los ultimos doce meses. El 52.7% de las mujeres consideraron su
      municipio como inseguro o muy inseguro. En el caso de los hombres, este
      porcentaje fue de 58.2%. Las mujeres victimas senalaron restricciones en la vida
      cotidiana significativas en comparacion con las no victimas. Con relacion a los
      hombres, el porcentaje de victimas con un alta restriccion de actividades fue
      mayor en los hombres victimas que en los hombres no victimas. En el grupo de
      mujeres victimizadas, el segmento de mujeres que optaron por mayores medidas de
      proteccion frente a la delincuencia fue mayor de lo esperado, mientras que las
      mujeres no victimas que asumieron menores medidas de proteccion fue menor de lo
      esperado. Estos mismos resultados se observaron en el grupo de los hombres.
      CONCLUSIONES: La experiencia de victimizacion lleva implicita una mayor
      percepcion de inseguridad. Sin embargo, el clima de inseguridad se encuentra
      diseminado en gran cantidad de la ciudadanos. Las diferencias de genero en un
      clima de alta criminalidad muestran la importancia de investigar a profundidad
      los roles de ambos sexos en la percepcion de inseguridad y los cambios en las
      rutinas.

PMID- 27706374
TI  - Portuguese version of the EUROPEP questionnaire: contributions to the
      psychometric validation.
AB  - OBJECTIVE: To assess the construct validity and reliability of the Portuguese
      version of the European Task Force on Patient Evaluation of General Practice Care
      questionnaire. METHODS: We applied the Portuguese version of the European Task
      Force on Patient Evaluation of General Practice Care to 392 users of 20 Family
      Health Units from the North of Portugal. The validity of the construct was
      evaluated by exploratory factor analysis, with the Principal Axis Factoring
      method, by orthogonal rotation (varimax procedure), by the Kaiser normalization
      criteria (eigenvalue >= 1). The factorability of the data matrix was verified by
      the Kaiser-Meyer-Olkin and Bartlett's sphericity test. We estimated the
      reliability by the indicator of internal consistency Cronbach's alpha. To analyze
      the correlations between satisfaction and loyalty, we used the Pearson
      correlations. The predictor effect of satisfaction on loyalty was analyzed by
      simple linear regression. RESULTS: Satisfaction presented five robust and well
      individualized dimensions - medical care, nursing care, clinical secretariat
      services, accessibility, and organization of services - with alpha values between
      0.86 and 0.97, good levels of internal consistency. The loyalty showed alpha
      value of 0.72, considered a reasonable internal consistency. The satisfaction was
      predictive of loyalty. CONCLUSIONS: The Portuguese European Task Force on Patient
      Evaluation of General Practice Care questionnaire is a robust and reliable
      instrument to measure the satisfaction and loyalty of users of the Family Health
      Units. OBJETIVO: Avaliar a validade de construto e fiabilidade da versao
      portuguesa do questionario European Task Force on Patient Evaluation of General
      Practice Care. METODOS: Foi aplicada a versao portuguesa do European Task Force
      on Patient Evaluation of General Practice Care a 392 utentes de 20 Unidades de
      Saude Familiar do norte de Portugal. A validade do construto foi avaliada por
      analise fatorial exploratoria, metodo Factoracao de Eixo Principal, por meio da
      rotacao ortogonal (procedimento varimax), pelo criterio de normalizacao de Kaiser
      (valor proprio >= 1). A fatoriabilidade da matriz dos dados foi verificada por
      meio do Kaiser-Meyer-Olkin e do teste de esfericidade de Bartlett. A fiabilidade
      foi estimada pelo indicador de consistencia interna alfa de Cronbach. Para
      analisar as correlacoes entre a satisfacao e a lealdade, utilizou-se as
      correlacoes de Pearson. O efeito preditor da satisfacao na lealdade foi analisado
      por meio de regressao linear simples. RESULTADOS: A satisfacao apresentou cinco
      dimensoes robustas e bem individualizadas - cuidados medicos, cuidados de
      enfermagem, servicos de secretariado clinico, acessibilidade e organizacao dos
      servicos - com valores de alfa entre 0,86 e 0,97, bons niveis de consistencia
      interna. A lealdade apresentou valor de alfa de 0,72, considerada consistencia
      interna razoavel. A satisfacao foi preditora da lealdade. CONCLUSOES: O
      questionario European Task Force on Patient Evaluation of General Practice Care
      portugues e um instrumento robusto e fiavel para medir a satisfacao e lealdade
      dos utentes das Unidades de Saude Familiar.

PMID- 27706375
TI  - Mortality and potential years of life lost by road traffic injuries in Brazil,
      2013.
AB  - OBJECTIVE: To estimate the potential years of life lost by road traffic injuries
      three years after the beginning of the Decade of Action for Traffic Safety.
      METHODS: We analyzed the data of the Sistema de Informacoes sobre Mortalidade
      (SIM - Mortality Information System) related to road traffic injuries, in 2013.
      We estimated the crude and standardized mortality rates for Brazil and geographic
      regions. We calculated, for the Country, the proportional mortality according to
      age groups, education level, race/skin color, and type or quality of the victim
      while user of the public highway. We estimated the potential years of life lost
      according to sex. RESULTS: The mortality rate in 2013 was of 21.0 deaths per
      100,000 inhabitants for the Country. The Midwest region presented the highest
      rate (29.9 deaths per 100,000 inhabitants). Most of the deaths by road traffic
      injuries took place with males (34.9 deaths per 100,000 males). More than half of
      the people who have died because of road traffic injuries were of black race/skin
      color, young adults (24.2%), individuals with low schooling (24.0%), and
      motorcyclists (28.5%). The mortality rate in the triennium 2011-2013 decreased
      4.1%, but increased among motorcyclists. Across the Country, more than a million
      of potential years of life were lost, in 2013, because of road traffic injuries,
      especially in the age group of 20 to 29 years. CONCLUSIONS: The impact of the
      high mortality rate is of over a million of potential years of life lost by road
      traffic injuries, especially among adults in productive age (early mortality), in
      only one year, representing extreme social cost arising from a cause of death
      that could be prevented. Despite the reduction of mortality by road traffic
      injuries from 2011 to 2013, the mortality rates increased among motorcyclists.
      OBJETIVO: Estimar os anos potenciais de vida perdidos por acidente de transporte
      terrestre apos tres anos do inicio da Decada de Acao pela Seguranca no Transito.
      METODOS: Foram analisados os dados do Sistema de Informacoes sobre Mortalidade
      correspondentes aos acidentes de transporte terrestre, em 2013. Foram calculadas
      as taxas de mortalidade bruta e padronizada para o Brasil e regioes geograficas.
      Foi calculada, para o Pais, a mortalidade proporcional segundo faixas etarias,
      escolaridade, raca/cor da pele e tipo ou qualidade da vitima enquanto usuaria da
      via publica. Foram estimados os anos potenciais de vida perdidos segundo sexo.
      RESULTADOS: A taxa de mortalidade, em 2013, foi de 21,0 obitos por 100 mil
      habitantes para o Pais. A regiao Centro-Oeste apresentou a taxa mais elevada
      (29,9 obitos por 100 mil habitantes). A maioria dos obitos por acidentes de
      transporte terrestre foi observada no sexo masculino (34,9 obitos por 100 mil
      homens). Mais da metade das pessoas que faleceram em decorrencia de acidentes de
      transporte terrestre eram da raca/cor da pele negra, adultos jovens (24,2%),
      individuos com baixa escolaridade (24,0%) e motociclistas (28,5%). A taxa de
      mortalidade, no trienio 2011 a 2013, apresentou reducao de 4,1%, mas aumentou
      entre os motociclistas. Em todo o Pais, mais de um milhao de anos potenciais de
      vida foram perdidos, em 2013, devido aos acidentes de transporte terrestre,
      especialmente na faixa etaria de 20 a 29 anos. CONCLUSOES: O impacto da alta taxa
      de mortalidade e de mais de um milhao de anos potenciais de vida perdidos por
      acidentes de transporte terrestre, principalmente entre adultos em idade
      produtiva (mortalidade precoce), em apenas um ano, representando extremo custo
      social decorrente de uma causa de obito que poderia ser prevenida. Apesar da
      reducao da mortalidade por acidentes de transporte terrestre de 2011 a 2013, as
      taxas de mortalidade aumentaram entre os motociclistas.

PMID- 27706376
TI  - On triatomines, cockroaches and haemolymphagy under laboratory conditions: new
      discoveries.
AB  - For a long time, haematophagy was considered an obligate condition for
      triatomines (Hemiptera: Reduviidae) to complete their life cycle. Today, the
      ability to use haemolymphagy is suggested to represent an important survival
      strategy for some species, especially those in genus Belminus. As Eratyrus
      mucronatus and Triatoma boliviana are found with cockroaches in the Blaberinae
      subfamily in Bolivia, their developmental cycle from egg to adult under a
      "cockroach diet" was studied. The results suggested that having only cockroach
      haemolymph as a food source compromised development cycle completion in both
      species. Compared to a "mouse diet", the cockroach diet increased: (i) the
      mortality at each nymphal instar; (ii) the number of feedings needed to molt;
      (iii) the volume of the maximum food intake; and (iv) the time needed to molt. In
      conclusion, haemolymph could effectively support survival in the field in both
      species. Nevertheless, under laboratory conditions, the use of haemolymphagy as a
      survival strategy in the first developmental stages of these species was not
      supported, as their mortality was very high. Finally, when Triatoma infestans,
      Rhodnius stali and Panstrongylus rufotuberculatus species were reared on a
      cockroach diet under similar conditions, all died rather than feeding on
      cockroaches. These results are discussed in the context of the ecology of each
      species.

PMID- 27706377
TI  - Molecular detection of flaviviruses and alphaviruses in mosquitoes (Diptera:
      Culicidae) from coastal ecosystems in the Colombian Caribbean.
AB  - Arboviruses belonging to the genera Flavivirus and Alphavirus were detected in
      mosquitoes in a rural area of San Bernardo del Viento (Cordoba, Colombia). A
      total of 22,180 mosquitoes were collected, sorted into 2,102 pools, and tested by
      generic/nested reverse transcription-polymerase chain reaction. Venezuelan equine
      encephalitis virus, dengue virus, West Nile virus, St. Louis encephalitis virus,
      yellow fever virus, and Culex flavivirus were detected and identified by
      sequencing. The detection of arboviral pathogens in this zone represents possible
      circulation and indicates a human health risk, demonstrating the importance of
      virological surveillance activities.

PMID- 27706378
TI  - The involvement of endothelial mediators in leprosy.
AB  - Leprosy is a chronic infectious disease that requires better understanding since
      it continues to be a significant health problem in many parts of the world.
      Leprosy reactions are acute inflammatory episodes regarded as the central
      etiology of nerve damage in the disease. The activation of endothelium is a
      relevant phenomenon to be investigated in leprosy reactions. The present study
      evaluated the expression of endothelial factors in skin lesions and serum samples
      of leprosy patients. Immunohistochemical analysis of skin samples and serum
      measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in
      77 leprosy patients and 12 controls. We observed significant increase of VCAM-1
      circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of
      VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p =
      0.02 for both) than healthy controls. Patients with type 1 reaction presented
      increased thrombomodulin serum levels, compared with non-reactional leprosy (p =
      0.02). In type 2 reaction, no significant modifications were observed for the
      endothelial factors investigated. The anti-inflammatory and antimicrobial
      activities of the endotfhelial factors may play key-roles in the pathogenesis of
      leprosy and should be enrolled in studies focusing on alternative targets to
      improve the management of leprosy and its reactions.

PMID- 27706379
TI  - Distribution and association between environmental and clinical isolates of
      Cryptococcus neoformans in Bogota-Colombia, 2012-2015.
AB  - The propagules of the fungal species Cryptococcus neoformans and C. gattii, whose
      varieties are distributed world wide, are the primary cause of cryptococcosis, a
      life threatening disease. The study of environmental and clinical isolates of
      Cryptococcosis is an important contribution to the epidemiology and ecology of
      the fungus. The aim of this work was to determine the presence of C. neoformans
      and C. gattii in the environment in Bogota, Colombia's capital city and to
      establish the relation between clinical and environmental isolates in the period
      2012-2015. From a total of 4.116 environmental samples collected between October
      2012 - March 2014, 35 were positive for C. neoformans var. grubii. From 55
      cryptococcosis cases reported in Bogota during 2012-2015, 49 isolates were
      recovered. From those, 94% were identified as C. neoformans var. grubii molecular
      type VNI; 4% as VNII and 1,2% as C. neoformans var neoformans VNIV. The 84
      detected clinical and environmental isolates studied had a similarity between 49
      100% according with molecular typing. The correlation between environmental and
      clinical samples confirms the hypothesis that patients acquire the disease from
      environmental exposure to the fungal propagules.

PMID- 27706380
TI  - Symbiont modulates expression of specific gene categories in Angomonas deanei.
AB  - Trypanosomatids are parasites that cause disease in humans, animals, and plants.
      Most are non-pathogenic and some harbor a symbiotic bacterium. Endosymbiosis is
      part of the evolutionary process of vital cell functions such as respiration and
      photosynthesis. Angomonas deanei is an example of a symbiont-containing
      trypanosomatid. In this paper, we sought to investigate how symbionts influence
      host cells by characterising and comparing the transcriptomes of the symbiont
      containing A. deanei (wild type) and the symbiont-free aposymbiotic strains. The
      comparison revealed that the presence of the symbiont modulates several
      differentially expressed genes. Empirical analysis of differential gene
      expression showed that 216 of the 7625 modulated genes were significantly
      changed. Finally, gene set enrichment analysis revealed that the largest
      categories of genes that downregulated in the absence of the symbiont were those
      involved in oxidation-reduction process, ATP hydrolysis coupled proton transport
      and glycolysis. In contrast, among the upregulated gene categories were those
      involved in proteolysis, microtubule-based movement, and cellular metabolic
      process. Our results provide valuable information for dissecting the mechanism of
      endosymbiosis in A. deanei.

PMID- 27706381
TI  - Culture media profoundly affect Candida albicans and Candida tropicalis growth,
      adhesion and biofilm development.
AB  - As there are sparse data on the impact of growth media on the phenomenon of
      biofilm development for Candida we evaluated the efficacy of three culture media
      on growth, adhesion and biofilm formation of two pathogenic yeasts, Candida
      albicans and Candida tropicalis. The planktonic phase yeast growth, either as
      monocultures or mixed cultures, in sabouraud dextrose broth (SDB), yeast nitrogen
      base (YNB), and RPMI 1640 was compared, and adhesion as well as biofilm formation
      were monitored using MTT and crystal violet (CV) assays and scanning electron
      microscopy. Planktonic cells of C. albicans, C. tropicalis and their 1:1 co
      culture showed maximal growth in SDB. C. albicans/C. tropicalis adhesion was
      significantly facilitated in RPMI 1640 although the YNB elicited the maximum
      growth for C. tropicalis. Similarly, the biofilm growth was uniformly higher for
      both species in RPMI 1640, and C. tropicalis was the slower biofilm former in all
      three media. Scanning electron microscopy images tended to confirm the results of
      MTT and CV assay. Taken together, our data indicate that researchers should pay
      heed to the choice of laboratory culture media when comparing relative
      planktonic/biofilm growth of Candida. There is also a need for standardisation of
      biofilm development media so as to facilitate cross comparisons between
      laboratories.

PMID- 27706382
TI  - First detection of natural infection of Aedes aegypti with Zika virus in Brazil
      and throughout South America.
AB  - Zika virus (ZIKV) has caused a major epidemic in Brazil and several other
      American countries. ZIKV is an arbovirus whose natural vectors during epidemics
      have been poorly determined. In this study, 1,683 mosquitoes collected in the
      vicinity of ZIKV suspected cases in Rio de Janeiro, Brazil, from June 2015 to May
      2016 were screened for natural infection by using molecular methods. Three pools
      of Aedes aegypti were found with the ZIKV genome, one of which had only one male.
      This finding supports the occurrence of vertical and/or venereal transmission of
      ZIKV in Ae. aegypti in nature. None of the examined Ae. albopictus and Culex
      quinquefasciatus was positive. This is the first report of natural infection by
      ZIKV in mosquitoes in Brazil and other South American countries. So far, Ae.
      aegypti is the only confirmed vector of ZIKV during the ongoing Pan-American
      epidemics.

PMID- 27706383
TI  - Impact of functional determinants on 5.5-year mortality in Amazon riparian
      elderly.
AB  - Objective To ascertain whether modifiable physical performance-based measurements
      predicted 5.5-year mortality in a riparian elderly cohort in the Amazon
      rainforest region. Methods A longitudinal study evaluating the impact of
      functional determinants on 5.5-year mortality in a riparian elderly cohort from
      Maues City in the state of Amazonas, Brazil, was performed. The study was a
      follow-up of a previous observational investigation that evaluated various
      fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged
      72.3 +/- 8.0 (60-99) years old. The cohort was selected for its adverse
      environmental conditions, which increased the risk of falls yet required
      maintenance of good physical condition for carrying out relatively rigorous daily
      activities, and restricted access to specialized health services. Official death
      records were obtained from the Maues Municipal Health Department. Results A total
      of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan
      Meier regression analysis showed significant association between Timed Up and Go
      (TUG) test scores >= 14 seconds and mortality risk, independent of sex, age, and
      other health variables. Conclusions The study results suggest that the TUG test
      can be used as an indicator for initiating therapeutic and preventive actions,
      including conducting exercises or physical activities adapted to the health and
      functional conditions of the elderly, by identifying elderly people with a higher
      relative risk of mortality.

PMID- 27706384
TI  - [The debate on regulating biotechnology drugs: Colombia in the international
      context].
AB  - In September 2014, Colombia issued standards for the evaluation of biological
      drugs within the framework of the marketing authorization process. The Colombian
      approach explicitly includes a fast track for evaluating competing biologicals,
      which caused great national and international controversy. This article explains
      the context that justifies the need for this fast-track approach, critically
      analyzes comparability as a paradigm for the evaluation of biogenerics, and shows
      that Colombia's position is not isolated and is based on global regulatory
      trends.

PMID- 27706385
TI  - Innovative in vitro methodologies for establishing therapeutic equivalence.
AB  - To improve the quality of pharmaceutical products in their markets, several Latin
      American countries have begun to require that new generic products demonstrate
      bioequivalence against innovator or reference products. However, given the number
      of products involved, it is not feasible to rely on clinical studies to comply
      with this requirement. Instead, it makes sense to adopt or develop strategies
      that are appropriate to the characteristics of the region. To streamline drug
      development and accelerate patients' access to quality drug products, 15 years
      ago the United States Food and Drug Administration (FDA) decided to grant
      exemptions from clinical bioequivalence studies (i.e., biowaivers) for certain
      types of drug products based on the Biopharmaceutics Classification System (BCS).
      Biowaivers can significantly reduce development time and cost and can also
      prevent unnecessary human exposure to potentially dangerous drugs while providing
      a robust, consistent standard for therapeutic equivalence of generic drug
      products. In addition, the limited success of translating in vitro dissolution
      data into in vivo performance can be enhanced using innovative tools such as the
      in vitro dissolution and absorption systems (IDAS). By integrating in vitro
      dissolution and permeability tests, these systems can provide useful insights for
      formulation development. A thorough assessment of the potential of in vitro
      techniques, along with formalization of their use through regulatory science
      initiatives when appropriate, may lead to cost-effective tools to help address
      some of the quality and regulatory challenges faced in the Latin American and
      Caribbean region.

PMID- 27706386
TI  - [Retrospective eco-epidemiology as a tool for the surveillance of leishmaniasis
      in Misiones, Argentina, 1920-2014].
AB  - A retrospective analytical method is presented, based on theoretical eco
      epidemiology, applied on a subnational spatial scale. This method was used here
      to describe scenarios for the transmission of leishmaniasis in the Argentine
      province of Misiones- bordering Brazil and Paraguay-and formed the basis for
      recommendations for surveillance and control appropriate to the subnational
      scale. An exhaustive search of the literature on leishmaniasis in the province
      was carried out. Three scenarios for the transmission of cutaneous leishmaniasis
      (CL) and visceral leishmaniasis (VL) were found, corresponding to three periods:
      from 1920 to 1997, during which the transmission of CL distributed over time and
      space was confirmed; 1998 to 2005, during which there were focal outbreaks of CL;
      and 2006 to 2014, during which outbreaks were also reported and the geographical
      dispersion of VL was documented. To describe the risk scenarios and the anthropic
      processes that produce them, the results were summarized and integrated into the
      social, historical, and bio-ecological context of each period. Surveillance and
      control recommendations are based on the territory studied. They include
      establishing active surveillance to monitor possible rising trends in parasitic
      and vector circulation, conducting studies of any focal outbreak in order to
      confirm indigenous transmission and severity. Also, it should be a legal
      requirement for persons responsible for projects that alter the environment to
      adopt additional control measures, such as studies assessing transmission risk,
      risk mitigation, early detection, and timely case management.

PMID- 27706387
TI  - Oxacillin disk diffusion testing for the prediction of penicillin resistance in
      Streptococcus pneumoniae.
AB  - Objective To 1) describe the correlation between the zones of inhibition in 1-ug
      oxacillin disk diffusion (ODD) tests and penicillin and ceftriaxone minimum
      inhibitory concentrations (MICs) of meningeal and non-meningeal strains of
      Streptococcus pneumoniae and 2) evaluate the usefulness of the ODD test as a
      predictor of susceptibility to penicillin in S. pneumoniae and as a quick and
      cost-effective method easily implemented in a routine clinical laboratory
      setting. Methods S. pneumoniae isolates from healthy nasopharyngeal carriers less
      than 2 years old, obtained in a multicentric cross-sectional study conducted in
      various Peruvian hospitals and health centers from 2007 to 2009, were analyzed.
      Using Clinical and Laboratory Standards Institute (CLSI) breakpoints, the
      correlation between the zones of inhibition of the ODD test and the MICs of
      penicillin and ceftriaxone was determined. Results Of the 571 S. pneumoniae
      isolates, 314 (55%) showed resistance to penicillin (MIC >= 0.12 ug/mL) and 124
      (21.7%) showed resistance to ceftriaxone (MIC >= 1 ug/mL). Comparison of the ODD
      test zones of inhibition and the penicillin MICs, using the CLSI meningeal
      breakpoints, showed good correlation (Cohen's kappa coefficient = 0.8239).
      Conclusions There was good correlation between ODD zones of inhibition and
      penicillin meningeal breakpoints but weak correlation between the ODD results and
      non-meningeal breakpoints for both penicillin and ceftriaxone. Therefore, the ODD
      test appears to be a useful tool for predicting penicillin resistance in cases of
      meningeal strains of S. pneumoniae, particularly in low- and middle- income
      countries, where MIC determination is not routinely available.

PMID- 27706388
TI  - [Emergence of CMY-2-type plasmid-mediated AmpC beta-lactamase in Shigella sonnei
      and Salmonella spp. in Costa Rica, 2003-2015].
AB  - Plasmid-mediated AmpC are enzymes belonging to the group of beta-lactamases and
      encoded by bla AmpC genes. Of these enzymes, those known as type CMY-2 are the
      most frequently reported worldwide. Detection of enterobacteria that produce CMY
      2-type plasmid-mediated AmpC is clinically important since the use of beta-lactam
      antibiotics can result in treatment failure. It is also important from a public
      health standpoint owing to the capacity for conjugative plasmid transfer to other
      enterobacteria, both within the community and in nosocomial environments. Thus,
      bacteria of this kind are considered to have clear epidemic potential. To
      investigate the circulation of this resistance mechanism among Salmonella and
      Shigella isolates in Costa Rica, from January 2003 to May 2015 we carried out a
      retrospective review of the data contained in the laboratory surveillance
      databases of the National Reference Bacteriology Center (CNRB) of the Costa Rican
      Nutrition and Health Research Institute (Inciensa). Over this period, 4363
      Shigella isolates and 1785 Salmonella isolates were examined. Among them, 15
      Shigella sonnei isolates and nine Salmonella isolates (four from human clinical
      specimens and five of avian origin) displayed a phenotype suspected of carrying
      plasmid-mediated AmpC. Polymerase chain reaction confirmed that all these
      isolates belong to type CMY-2. In light of these results, we recommend that the
      microbiology laboratories in the national network continue to conduct
      surveillance and confirm any suspicious isolates using phenotypic and molecular
      methods. This is particularly relevant when dealing with bacterial isolates from
      extraintestinal infections so as to prevent treatment failure.

PMID- 27706389
TI  - Agriculture, food, and nutrition interventions that facilitate sustainable food
      production and impact health: an overview of systematic reviews.
AB  - Objectives To identify the agriculture, food, and nutrition security
      interventions that facilitate sustainable food production and have a positive
      impact on health. Methods Systematic review methods were used to synthesize
      evidence from multiple systematic reviews and economic evaluations through a
      comprehensive search of 17 databases and 10 websites. The search employed a pre
      defined protocol with clear inclusion criteria. Both grey and peer-reviewed
      literature published in English, Spanish, and Portuguese between 1 January 1997
      and November 2013 were included. To classify as "sustainable," interventions
      needed to aim to positively impact at least two dimensions of the integrated
      framework for sustainable development and include measures of health impact.
      Results Fifteen systematic reviews and seven economic evaluations met the
      inclusion criteria. All interventions had some impact on health or on risk
      factors for health outcomes, except those related to genetically modified foods.
      Impact on health inequalities was rarely measured. All interventions with
      economic evaluations were very cost-effective, had cost savings, or net benefits.
      In addition to impacting health (inclusive social development), all interventions
      had the potential to impact on inclusive economic development, and some, on
      environmental sustainability, though these effects were rarely assessed.
      Conclusions What is needed now is careful implementation of interventions with
      expected positive health impacts but with concurrent, rigorous evaluation.
      Possible impact on health inequalities needs to be considered and measured by
      future primary studies and systematic reviews, as does impact of interventions on
      all dimensions of sustainable development.

PMID- 27706390
TI  - [An assessment of fiscal space for public health in Peru].
AB  - Objective To assess the fiscal space for public health in Peru so as to attain
      the goal of raising health spending to 6% of gross domestic product, as agreed
      upon by member countries of the Pan American Health Organization in 2014. Methods
      The main sources of fiscal space were identified by means of a thorough
      literature review. Technical feasibility was determined from statistics and
      national and international surveys and by reviewing various documents and
      official reports. Political feasibility was ascertained by studying policy
      guidelines. Results The sources showing the greatest technical and political
      feasibility are economic growth, a broadening of the personal income tax base,
      and an increase in tobacco-specific taxes. Decreasing informality in the job
      market and increasing contributory coverage are considered to be less politically
      feasible, but there is ample technical space for these measures. Conclusions
      There is enough fiscal space to allow for an increase in public health spending.
      Nevertheless, the 6% target will be reached only if the timeline is extended, tax
      revenues are increased, and informality in the job market is reduced.

PMID- 27706391
TI  - [Kidney disease in Colombia: Priority for risk management].
AB  - Objective To describe the demographic and clinical manifestations of patients
      with chronic kidney disease (CKD), arterial hypertension, and/or diabetes
      mellitus, and to determine the association between the presence of these
      pathologies and the development of CKD. Methods Analytic and cross-sectional
      study. The information, with a cutoff date of 30 June 2013, comes from the
      integrated database of CKD and patients with hypertension and diabetes, which the
      Colombian payer entities provided to the national fund for high-cost diseases
      (Cuenta de Alto Costo). A descriptive analysis was conducted and the prevalence
      of CKD and stage 5 CKD was determined. Crude odds ratios (OR) were used to
      determine the association between CKD and age, sex, and diabetes. Results
      2,599,419 records were analyzed, of which 40% corresponded to people with CKD.
      Overall, 74.9% of the population had hypertension and 6.4% had diabetes. The
      prevalence of CKD was 2.81%, with 94.3% of patients in stages 1 to 3. In patients
      with diabetes, the risk of presenting CKD is 1.03 (confidence interval of 95%
      [CI95%] 1.016-1.043). Among persons over 60 years of age, the risk of CKD is 2.15
      (CI95% 2.140-2.167). Conclusions 33.4% of patients with hypertension or diabetes
      have not been studied to determine the presence or absence of CKD. It is a
      priority to implement strategies for secondary and primary prevention in order to
      prevent the progression of CKD and reduce the prevalence of risk factors such as
      hypertension and diabetes.

PMID- 27706392
TI  - [Control of potential risk in blood establishments in Brazil: a strategy for
      regulating authorities].
AB  - Objective To describe the sanitary status of Brazilian blood establishments (BE)
      assessed by the national health surveillance system in 2013. Method In the
      present descriptive study, the sanitary profile of BE was assessed using the
      Blood Establishment Potential Risk Assessment Method (Metodo de Avaliacao de
      Risco Potencial de Servicos de Hemoterapia, MARPSH), developed by the National
      Sanitary Surveillance Agency (Anvisa). The MARPSH involves the evaluation of 471
      structure and process items to produce an assessment of potential risk associated
      with critical control points in the blood cycle (vein-to-vein). Based on this
      assessment, BE are classified into five risk categories: low, medium-low, medium,
      medium-high, and high. The results were analyzed regarding the type of service
      (considering all levels, from coordinating centers to collection units), type of
      financing (public/private) and geographic region. Results Of the existing BE, 1
      212 (60%) were assessed in 2013. Of these, 81% met >= 70% of the sanitary
      requirements (satisfactory status, corresponding to medium, medium-low, and low
      risk categories). Transfusion agencies (hospital units with the role of storing,
      running compatibility tests between donors and recipients, and transfusing blood
      components) and public establishments had the highest number of non-conformity
      structure and process items. Conclusion The use of the MARPSH facilitated the
      assessment of BE in Brazil and revealed objective opportunities for improvement.
      These gaps should be addressed by regulating authorities, especially in public
      services.

PMID- 27706393
TI  - Aquatic life protection index of an urban river Bacanga basin in northern Brazil,
      Sao Luis - MA.
AB  - Bacanga River Basin faces environmental problems related to urbanization and
      discharge of untreated domestic sewage, which compromise its ecosystem health.
      Due to the small number of studies that assessed its water quality, the present
      study aimed to assess the current status of this ecosystem based on the aquatic
      life protection index. Samples were carried out every two months, in a total of
      six events, in six sites along the basin, where the water samples were collected
      to assess physicochemical parameters and calculate the trophic state index and
      the index of minimum parameters for the protection of aquatic communities. The
      data were also compared with values determined by the resolution National
      Environment Council - CONAMA 357/05. Our results reveal significant changes in
      the water quality of Bacanga River Basin. An increase in nutrients and
      chlorophyll-a concentration led it to eutrophication. The surfactant values were
      high and put in danger the aquatic biota. Dissolved oxygen rates were below the
      values allowed by the resolution in most sites sampled. The current water quality
      is terrible for the protection of aquatic life in 61.92% of the sites sampled.

PMID- 27706394
TI  - Variation of age and total length in Sotalia guianensis (Van Beneden, 1864)
      (Cetacea, Delphinidae), on the coast of Espirito Santo state, Brazil.
AB  - Variations of age and total length of Sotalia guianensis from the state of
      Espirito Santo, Brazil, were evaluated. Specimens were found stranded. Age and
      total length of 44 Guiana dolphins were assessed based on tooth analysis. Age
      varied between 0.5 year and 33 years (mean = 8.23 years). Most specimens were
      between zero and 6 years old (47%). Total length varied from 119 cm to 198 cm,
      with mean of 172.52 cm. Asymptotic length was reached at 185 cm and approximately
      5-6 years of age. Mean total length and age were higher than in other regions of
      the distribution range of the species. Nevertheless, more studies have to be
      carried out to evaluate the morphological variations in S. guianensis populations
      in the study area and Brazil.

PMID- 27706395
TI  - In vitro susceptibility of nematophagous fungi to antiparasitic drugs:
      interactions and implications for biological control.
AB  - The fast anthelmintic resistance development has shown a limited efficiency in
      the control of animal's endoparasitosis and has promoted research using
      alternative control methods. The use of chemicals in animal anthelmintic
      treatment, in association with nematophagous fungi used for biological control,
      is a strategy that has proven to be effective in reducing the nematode population
      density in farm animals. This study aims to verify the in vitro susceptibility of
      the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and
      Paecilomyces lilacinus against the antiparasitic drugs albendazole,
      thiabendazole, ivermectin, levamisole and closantel by using the Minimum
      Inhibitory Concentration (MIC). MICs ranged between 4.0 and 0.031 ug/mL for
      albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 ug/mL for
      levamisole, and between 0.625 and 0.034 ug/mL for closantel. The results showed
      that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous
      fungi, which could compromise their action as agents of biological control. D.
      flagrans was the most susceptible species to all drugs.

PMID- 27706396
TI  - Wound-Healing potential of Sebastiania hispida (Mart.) Pax (Euphorbiaceae)
      ointment compared to low power laser in rats.
AB  - Impaired wound healing represents a serious complication in some pathologies and
      the use of plant extracts has proved to improve tissue repair. The objectives of
      this study were to evaluate the healing potential of the ointment of Sebastiana
      hispida compared with Aluminum-Gallium Indium-Phosphide Laser (InGaAlP) in
      surgically induced wounds in rats and to perform the phytochemical analysis. The
      phytochemical analysis was performed in the classic way and also by HPLC. A
      controlled study was developed with 80 rats (200-250 g) in which a linear
      excision was performed in the dorsal region after shaving, measuring 2 cm * 1 cm
      (epidermis and dermis) exposing the muscle fascia. The rats were randomly divided
      into four groups of twenty animals each. The experimental groups (n = 5) were G1
      (Saline); G2 (crude methanol plant extract 2% + Carbopol Gel 98%); G3 (crude
      methanol plant extract 2% + lanolin/vaseline) and G4 (laser). The incision
      healing processes were monitored during 3, 7, 14 and until 21 days after
      excision. The histologic parameters evaluated were Collagen fiber types,
      microscopic examination and neovascularization. There was a significant increase
      in the deposition of collagen fibers, as evidenced by a better organized
      epithelial tissue, keratinized and showing greater proliferation of new blood
      vessels in the inflammatory phase in the group treated with both the extract and
      laser. The results were correlated to the phenolic derivatives found after
      qualitative and quantitative analysis. These compounds were considered
      responsible for the healing process. The topical treatment with S. hispida
      leaves, in the two different formulations, was more effective than the
      application of the laser (Ingan ALP) 660 nm in the model used.

PMID- 27706397
TI  - Vegetative propagation of Plukenetia polyadenia by cuttings: effects of leaf area
      and indole-3-butyric acid concentration.
AB  - The seeds of Plukenetia polyadenia have high levels of unsaturated fatty acids
      and are used as medicine and food for native people in the Peruvian and Brazilian
      Amazon. The objective of this study was to develop a method for vegetative
      propagation of Plukenetia polyadenia by rooting of cuttings. The experiment was
      laid out in a randomized complete block design with 12 treatments and 3
      replications of 8 cuttings, in a 3 * 4 factorial arrangement. The factors were: 3
      levels of leaf area (25, 50 and 75%) and 3 indole-3-butyric acid - IBA
      concentrations (9.84, 19.68 and 29.52mM) and a control without IBA. Data were
      submitted to analysis of variance and means were compared by Tukey test at 5%
      probability. Our results show that the use of cuttings with 50% of leaf area and
      treatment with 29.52mM of IBA induced high percentages of rooting (93%) and the
      best root formation. Vegetative propagation of Plukenetia polyadenia by cuttings
      will be used as a tool to conserve and propagate germplasm in breeding programs.

PMID- 27706398
TI  - Sharing regulatory data as tools for strengthening health systems in the Region
      of the Americas.
AB  - Regulatory transparency is an imperative characteristic of a reliable National
      Regulatory Authority. In the region of the Americas, the process of building an
      open government is still fragile and fragmented across various Health Regulatory
      Agencies (HRAs) and Regional Reference Authorities (RRAs). This study assessed
      the transparency status of RRAs, focusing on various medicine life-cycle
      documents (the Medicine Dossier, Clinical Trial Report, and Inspection Report) as
      tools for strengthening health systems. Based on a narrative (nonsystematic)
      review of RRA regulatory transparency, transparency status was classified as one
      of two types: public disclosure of information (intra-agency data) and data- and
      work-sharing (inter-agency data). The risks/benefits of public disclosure of
      medicine-related information were assessed, taking into account 1) the
      involvement and roles of multiple stakeholders (health care professionals,
      regulators, industry, community, and academics) and 2) the protection of
      commercial and personal confidential data. Inter-agency data- and work-sharing
      was evaluated in the context of harmonization and cooperation projects that focus
      on regulatory convergence. Technical and practical steps for establishing an
      openness directive for the pharmaceutical regulatory environment are proposed to
      improve and strengthen health systems in the Americas. Addressing these
      challenges requires leadership from entities such as the Pan American Health
      Organization to steer and support collaborative regional alliances that advance
      the development and establishment of a trustworthy regulatory environment and a
      sustainable public health system in the Americas, using international successful
      initiatives as reference and taking into account the domestic characteristics and
      experiences of each individual country.

PMID- 27706399
TI  - [Proposed model for managing drugs used for unregistered indications in
      Colombia].
AB  - The use of drugs for unregistered indications, known as "off-label" use, is a
      practice that creates problems of rational use and access when other options are
      not available. Health systems should address this situation, particularly in
      connection with decisions concerning coverage, while trying to minimize health
      risks and clearly define the roles and responsibilities of the parties involved.
      Colombia's Ministry of Health and Social Protection (MinSalud), together with the
      National University of Colombia and national experts, developed a proposal for a
      model for managing drugs being used for unregistered indications (off-label) and
      their potential reimbursement with public resources, taking into account
      international practices and country characteristics. The management model is non
      punitive and is geared toward promoting the rational use of these drugs so that
      barriers to access are reduced whenever their use is supported by solid
      scientific evidence. The model addresses patient safeguards in the bioethical
      domain and the roles and responsibilities of the prescriber and government
      entities.

PMID- 27706400
TI  - [Regulation of medical devices in the Region of the Americas].
AB  - Objective To describe and analyze the current status of and the challenges
      involved in the regulation of medical devices in the Region of the Americas and
      to present the results of the regional mapping exercise, progress toward the
      development of advanced assessment indicators, and the achievements of the
      Regional Working Group. Methods Creating a regional profile on the regulation of
      medical devices in the Americas is a priority for the Working Group. To this end
      a tool composed of 45 questions organized into six sections was developed and
      distributed among 15 countries for self-assessment (the participation rate was
      100%). Based on the data received, nine basic indicators were established and an
      agreement was reached to develop advanced indicators for measuring the extent to
      which regulatory programs for medical devices were being implemented. Results Of
      the 15 countries, 93% have an agency in charge of regulating medical devices. An
      analysis of individual country performance shows wide variability, with some
      countries meeting all indicators and others meeting as few as 11%. The mapping
      also made it possible to generate information on collaborative partnerships,
      training, and regulation. Conclusions The results show significant heterogeneity
      at the regional level. Implementation of advanced indicators will help to
      identify areas of opportunity and strengths for the development of the regulatory
      profile. Although progress has been made toward strengthening regulatory programs
      for medical devices, remaining gaps need to be bridged through strategies and
      initiatives to be led by the Working Group.

PMID- 27706401
TI  - [Regulatory Center for Medicines of the Bolivarian Alliance for the Peoples of
      the Americas (ALBAMED): a new initiative for regulatory integration].
AB  - Objective To review, organize, and share the experience of the regulatory
      authorities of countries involved in a project headed by the Bolivarian Alliance
      for the Peoples of Americas (ALBA) for the establishment of a regulatory center
      (ALBAMED) and a single registry to facilitate access to essential medicines while
      ensuring quality, safety, and effectiveness, as well as to demonstrate how the
      construction of this forum for regional cooperation has benefited these
      authorities and their respective regulatory systems. Methods A descriptive,
      longitudinal, and retrospective study of ALBAMED's activities between 2009 and
      2014 using published and archived materials. The level of agreement was
      determined by means of surveys; and joint development of standards, knowledge
      transfer, and the identification of best practices were assessed. Results The
      regulatory authorities of Bolivia, Cuba, Ecuador, Nicaragua, and Venezuela
      participated in the project. Twenty-five comparative assessments of the status of
      regulation in nine key areas were carried out. Six coordination meetings and four
      specialized workshops were held. More than 130 provisions and procedures were
      approved, having been developed specifically for the ALBAMED Regulatory Center or
      adopted from guidelines issued by the World Health Organization and the Pan
      American Health Organization. Conclusions The mapping exercise for a regulatory
      center and supranational registry for ALBA countries has enhanced the performance
      of participating authorities and strengthened drug regulatory systems through the
      development and selection of the standards to be applied, knowledge transfer, and
      the promotion of best practices.

PMID- 27706402
TI  - [Sanitary regulation as part of health policy in Brazil: gaps and challenges].
AB  - Objective To outline and discuss the main challenges for sanitary regulation
      contained in the federal-level Brazilian health policy. Methods For the present
      qualitative study, based on the analysis of public policies, information was
      collected from documents and interviews. Document analysis provided a historical
      overview of the insertion of sanitary regulation into the Brazilian health policy
      between 1999 and 2009 (first decade of existence of the national health
      surveillance agency, Anvisa). In addition, 13 interviews were carried out with
      actors selected for their historical, technical, or academic role in the field.
      Content analysis was used to define themes emerging from the materials analyzed
      with a focus on the "content" category, which refers to strategic and operational
      guidelines of policy programs, projects, initiatives, and normative framework.
      Results Content analysis revealed five themes that reflect the challenges to
      sanitary regulation in Brazil: 1) objects under regulation treated as isolated
      cases; 2) a Brazilian-specific model of sanitary regulation that is different
      from other international models; 3) ignorance regarding the role of sanitary
      surveillance in health care; 4) absence of an information system; and 5) absence
      of performance indicators and assessment tools. Conclusions Sanitary surveillance
      must have a mission that is disentangled from inspection tasks to become an
      effective instrument of health protection. For that, an information system that
      brings the National Sanitary Surveillance System together toward major objectives
      is essential. The adoption of tools for assessment of action is also required,
      with the establishment of adequate indicators.

PMID- 27706403
TI  - Establishing a regulatory value chain model: An innovative approach to
      strengthening medicines regulatory systems in resource-constrained settings.
AB  - Medicines Regulatory Authorities (MRAs) are an essential part of national health
      systems and are charged with protecting and promoting public health through
      regulation of medicines. However, MRAs in resource-constrained settings often
      struggle to provide effective oversight of market entry and use of health
      commodities. This paper proposes a regulatory value chain model (RVCM) that
      policymakers and regulators can use as a conceptual framework to guide
      investments aimed at strengthening regulatory systems. The RVCM incorporates nine
      core functions of MRAs into five modules: (i) clear guidelines and requirements;
      (ii) control of clinical trials; (iii) market authorization of medical products;
      (iv) pre-market quality control; and (v) post-market activities. Application of
      the RVCM allows national stakeholders to identify and prioritize investments
      according to where they can add the most value to the regulatory process.
      Depending on the economy, capacity, and needs of a country, some functions can be
      elevated to a regional or supranational level, while others can be maintained at
      the national level. In contrast to a "one size fits all" approach to regulation
      in which each country manages the full regulatory process at the national level,
      the RVCM encourages leveraging the expertise and capabilities of other MRAs where
      shared processes strengthen regulation. This value chain approach provides a
      framework for policymakers to maximize investment impact while striving to reach
      the goal of safe, affordable, and rapidly accessible medicines for all.

PMID- 27706404
TI  - Regionalization as an approach to regulatory systems strengthening: a case study
      in CARICOM member states.
AB  - Improving basic capacities for regulation of medicines and health technologies
      through regulatory systems strengthening is particularly challenging in resource
      constrained settings. "Regionalization"-an approach in which countries with
      common histories, cultural values, languages, and economic conditions work
      together to establish more efficient systems-may be one answer. This report
      describes the Caribbean Regulatory System (CRS), a regionalization initiative
      being implemented in the mostly small countries of the Caribbean Community and
      Common Market (CARICOM). This initiative is an innovative effort to strengthen
      regulatory systems in the Caribbean, where capacity is limited compared to other
      subregions of the Americas. The initiative's concept and design includes a number
      of features and steps intended to enhance sustainability in resource-constrained
      contexts. The latter include 1) leveraging existing platforms for centralized
      cooperation, governance, and infrastructure; 2) strengthening regulatory
      capacities with the largest potential public health impact; 3) incorporating
      policies that promote reliance on reference authorities; 4) changing the system
      to encourage industry to market their products in CARICOM (e.g., using a
      centralized portal of entry to reduce regulatory burdens); and 5) building human
      resource capacity. If implemented properly, the CRS will be self-sustaining
      through user fees. The experience and lessons learned thus far in implementing
      this initiative, described in this report, can serve as a case study for the
      development of similar regulatory strengthening initiatives in resource
      constrained environments.

PMID- 27706405
TI  - Strengthening of regulatory systems for medicines in the Americas.

PMID- 27706406
TI  - [Strengthening health regulation in the Americas: regulatory authorities of
      regional reference].
AB  - Health technology regulation and quality assurance are critical to the
      development of national pharmaceutical policies, and implementing these actions
      is the responsibility of national regulatory authorities, whose level of
      development and maturity affect the quality, safety, and effectiveness of the
      products made available to the public. On the initiative of the regulatory
      authorities themselves, together with the Pan American Health Organization, the
      Region of the Americas promotes the strengthening of health regulation through an
      evaluation and certification process that allows for the designation of
      regulatory authorities of regional reference for drugs and biological products.
      Over the period from its implementation to the present, six authorities have been
      certified and one is in the process of obtaining certification. These authorities
      work jointly and promote dialogue and regulatory convergence, information-sharing
      to facilitate regulatory decision making, and regional cooperation to support the
      establishment of other authorities in the Region--actions having direct impact on
      access to effective and quality-assured health technologies. Their combined
      efforts have led to the recognition of this process of evaluation and
      certification by the World Health Organization (WHO). Among the actions resulting
      from the International Consultation on Regulatory Systems Strengthening, WHO
      recommended taking a close look at this model to assess its potential scale-up at
      the global level.

PMID- 27706407
TI  - [South-South cooperation to strengthen the medicines control laboratories of the
      Caribbean community (CARICOM)].
AB  - Objective To describe the benefits obtained through South-South and triangular
      cooperation as a potential tool for strengthening medicine quality control in
      official medicines control laboratories (OMCLs) of the Region of the Americas.
      Methods Descriptive study of the project for strengthening drug quality control
      in OMCLs of the Caribbean community (CARICOM). Results Staff members of
      Argentina's National Administration for Drugs, Food, and Medical Technology
      (ANMAT) provided training to professionals from Guyana, Jamaica, Suriname, and
      Trinidad and Tobago. The project was funded by the Argentine Fund for South-South
      and Triangular Cooperation (FO.AR) and coordinated by the Pan American Health
      Organization (PAHO). Documents on good laboratory practice (GLP) developed by the
      World Health Organization (WHO) and the Pan American Network for Drug Regulatory
      Harmonization (PANDRH) were reviewed, and the area of physical and chemical
      controls was strengthened, primarily for drugs to treat tuberculosis, malaria,
      and HIV/AIDS, all of which are strategically important to those countries.
      Conclusion This type of collaboration makes it possible to share experiences,
      optimize resources, harmonize procedures and regulations, and strengthen human
      resource capacities. In addition, it is a valuable tool for reducing asymmetries
      in various areas among the different countries of our Region.

PMID- 27706408
TI  - Improving safety, quality and efficacy of medicines in the Americas.

PMID- 27706409
TI  - Regulatory convergence and harmonization: barriers to effective use and adoption
      of common standards.
AB  - Objective To evaluate 1) the level of use and adoption of eight Technical
      Documents (TDs) published by the Pan American Network for Drug Regulatory
      Harmonization (PANDRH) member states and 2) identify the hurdles that can prevent
      countries from successfully adopting a common standard. Methods An in-depth
      analysis of the incorporation of PANDRH Technical Document No. 1 ("TDNo1")
      recommendations in member states' national requirements was carried out. Results
      The results illustrate the role of PANDRH in promoting convergence/harmonization
      among its members. Conclusions The study results show that the rate of use of TDs
      varied greatly by product/area and country. Timing, TD content, and product/area,
      and, more importantly, national capacities, are critical determinants of the
      level of TD guideline adoption. While PANDRH TDs have proven instrumental for the
      harmonization/convergence of member states' national requirements, as shown by
      the level of convergence across a majority of the national requirements issued
      for vaccine licensing, several countries had yet to incorporate common standards
      due, in large part, to weak national regulatory capacities. Therefore,
      harmonization/convergence initiatives should include the strengthening of
      national regulatory capacities as part of their core strategy, which will, in
      turn, allow for the incorporation and deployment of common standards in all
      participating countries.

PMID- 27706410
TI  - [Strengthening the Pan American Network of Official Medicines Control
      Laboratories].
AB  - Objective Official Medicines Control Laboratories (OMCLs) play a critical role in
      quality assurance. The objective of this work is to describe the actions taken by
      the Pan American Health Organization (PAHO) to strengthen OMCLs in the Region of
      the Americas. Methods A descriptive study was conducted by the External Quality
      Control Program (EQCP) to assess the diagnostic and overall performance of OMCLs;
      human resource training; measures adopted by the Pan American Network for Drug
      Regulatory Harmonization (PANDRH) to facilitate prequalification of OMCLs by the
      World Health Organization (WHO) as reference laboratories for United Nations
      agencies; and the technical documents developed by the Working Group on Good
      Laboratory Practice (WGGLP) and their level of implementation. Results The Pan
      American Network of OMCLs, established in 2005, is currently composed of 28 OMCLs
      in 23 countries. The EQCP assessed the performance of OMCLs in ten stages; 784
      professionals, 313 of them from OMCLs, received training in good laboratory
      practice (GLP). Guidelines for external evaluation and self-evaluation were
      developed. Six OMCLs attained WHO prequalification and nine became regional
      reference laboratories. Conclusions The initiatives undertaken made it possible
      to strengthen the activity of the OMCLs and to train human resources.
      Furthermore, they provided tools for continuous improvement through external
      evaluation and self-evaluation.

PMID- 27706411
TI  - Fifty years of the European medicines regulatory network: reflections for
      strengthening intra-regional cooperation in the Region of the Americas.
AB  - This report considers how the experience of the European regulatory system might
      be applied to help strengthen the regulatory systems for medicines in the Region
      of the Americas. The work of the European Medicines Agencies (EMA) is carried out
      through its scientific committees, composed of members from European Economic
      Area countries. A robust legal framework allows EMA to coordinate resources from
      Member States' competent authorities, including, for example, assisting candidate
      countries as they prepare to join the European Union (EU). Capacity-building
      programs help countries adjust their regulatory systems ahead of full
      participation in the European medicines regulatory network. These programs
      facilitate adoption of common technical requirements, identify areas where action
      might be needed to ensure the smooth transposition of EU pharmaceutical law into
      national legislation, and prepare candidate countries for participation in EMA
      committees and the European regulatory network. The methodology of these programs
      could be of potential interest to the Pan American Health Organization (PAHO),
      the Regional Office of the World Health Organization for the Americas. Given
      resolutions adopted by the World Health Assembly and the PAHO Directing Council,
      there is a strong indication that the countries of the Region of the Americas
      wish to assemble a system that uses the existing regulatory capacity of some
      countries to strengthen local regulatory capacities in others.

PMID- 27706412
TI  - [Regulatory Program for Medical Devices in Cuba: experiences and current
      challenges].
AB  - Regulatory control of medical devices in Cuba is conducted through a system based
      on the Regulatory Program for Medical Devices as a way to ensure the safety,
      efficacy, and effectiveness of these technologies, which are in use by the
      National Health System. This program was launched in 1992, when the Regulations
      for State Evaluation and Registration of Medical Devices were approved. Its
      successive stages and the merging of regulatory activities for drugs and medical
      equipment have meant progress toward stronger, more transparent strategies and
      greater control of industry and the National Health System. Throughout its course
      the Cuban program has met with challenges and difficulties that it has addressed
      by drawing on its own experiences. During the new period, the greatest challenges
      revolve around ensuring that regulatory systems incorporate scientific
      evaluation, risk levels, maximum rigor through the use of technical standards,
      and the implementation of international recommendations, together with the
      application of the ISO 13485 certification scheme, enhanced market monitoring,
      and classification of medical devices in accordance with their relevance to the
      country's national health policies. From the regional standpoint, the greatest
      challenge lies in working toward regulatory convergence. The Collaborating Centre
      for the Regulation of Health Technologies will support the proposed regulatory
      strategy and established regional priorities, in particular in connection with
      the implementation of actions involving medical devices.

PMID- 27706413
TI  - [Convergence of healthcare regulation in the Americas: history, development, and
      new challenges].
AB  - The present article describes the changing relationship among healthcare
      regulatory authorities in various international settings, with special emphasis
      on the Americas. As other sectors, healthcare also faces the need to regulate
      international practices, while at the same time taking into consideration the
      specific realities of each country. Regulatory convergence - a movement towards
      technical alignment to enable the adoption of local regulatory mechanisms that
      take into account internationally recognized standards and principles to promote
      a single sanitary goal - has emerged as a means to address this challenge.
      Organizations that already use this tool, such as the International Conference of
      Drug Regulatory Authorities (ICDRA), Pan American Network for Drug Regulatory
      Harmonization (PANDRH), International Generic Drug Regulators Programme (IGDRP),
      and the International Medical Device Regulators Forum (IMDRF), among others, are
      currently working to gather knowledge, data, and specialists from different
      countries to build an international technical and scientific standard that can be
      used for decision-making by local regulators. This would ensure convergence of
      national regulations despite the need to adapt international standards to local
      needs, structure, and capacities. The most recent resolutions issued by the World
      Health Organization recognize the need to bring regulatory systems closer to the
      reality of national healthcare systems, and underscore the advantages of using
      existing local guidelines as input for cooperation with regulatory authorities.

PMID- 27706414
TI  - Olfactory dysfunction as a marker of multiple sclerosis progression.

PMID- 27706415
TI  - Congenital myasthenic syndromes and myasthenia gravis are challenging diagnoses
      in neurological practice.

PMID- 27706416
TI  - Olfactory alterations in patients with multiple sclerosis.
AB  - Objective: To assess olfactory function using the Connecticut test and verify
      correlations between olfactory alteration, disease duration and the Expanded
      Disability Status Scale (EDSS). Methods: One hundred MS patients and 100 healthy
      control patients responded to a questionnaire. Those with olfactory alteration
      underwent a facial CT to exclude other causes. Results: Thirty-two percent of
      patients showed alterations, compared with 3% in the healthy control group.
      Patients having EDSS above 4, showed a 5.2-times increased risk of dysfunction.
      Patients over 38 years of age have a 2.2-times increased risk over younger
      patients. Conclusions: Because MS patients are likely to experience olfactory
      alterations, this study is a useful tool in follow-up care, although more studies
      are necessary to evaluate the correlations in MS evolution.

PMID- 27706417
TI  - Sleep disorder investigation might be considered to be mandatory in attention
      deficit/hyperactivity disorder guideline.
AB  - Objective: To determine the prevalence of obstructive sleep apnea (OSA) in
      children with attention deficit/hyperactive disorder (ADHD) and compare amplitude
      and latency of the P300 potential among children with and without OSA. Method:
      Sixty-one children with ADHD underwent oddball auditory attention tests for
      detection of P300 (ERPs) followed by an all-night polysomnography. The children
      were divided in two groups, those with and without OSA. Results: Significant
      decreased amplitude of the P300 potential was observed in children with OSA when
      compared with children without OSA. Conclusion: The study showed that sleep
      fragmentation as a result of OSA can exacerbate the attention disorder that
      characterizes ADHD, and highlights the importance of assessing the presence of
      OSA in the differential diagnosis of children with attention deficits.

PMID- 27706419
TI  - Elastomers three-dimensional biomodels proven to be a trustworthy representation
      of the angiotomographic images.
AB  - Methods: 3D biomodels were printed with flexible material (elastomer) using
      angiotomographic DICOM acquired images and compared to 3D digital subtraction
      angiography (DSA) images. Results: 3D biomodels represented the aneurysm
      angioarchitecture exactly, especially the neck and domus features. Conclusion:
      Elastomers 3D biomodels proved to be a trustworthy representation of the
      angiotomographic images and could be used to help surgical planning in IA
      treatment.

PMID- 27706418
TI  - Association between clinical condition and F-waves changes in the acute phase of
      stroke.
AB  - Objective: To relate F-waves with clinical and laboratory exams in the acute
      phase of stroke. Methods: Inclusion criteria for this cross-sectional study were:
      hemiplegia, absence of previous cranial trauma, myopathy, diabetes, alcoholism or
      other known causes of peripheral neuropathy, and normal sensory and motor
      conduction. The National Institutes of Health Stroke Scale (NIHSS) score,
      glycemia, glucosilate hemoglobin, and CPK were obtained at admission by routine
      blood exams. After hospital admission, the F-wave latencies and persistence were
      obtained from the deep peroneal nerve using symmetrical techniques. Results:
      Evaluation of 20 individuals - mean age 66 years, 50% male and 85% Caucasian -
      showed association of F-wave persistence with glycemia (r = 0.71; p < 0.001) and
      NIHSS categorized (NIHSS 1-7 = 65.0 x NIHSS 9-23 = 100; p = 0.004). Multivariate
      analysis found only association of F-wave persistence with glycemia beta = 0.59
      (0.44-0.74); p < 0.001. Conclusion: The increase in the persistence of F-waves
      are associated with hyperglycemia in the acute phase of stroke.

PMID- 27706420
TI  - Analysis of the albumin level, neutrophil-lymphocyte ratio, and platelet
      lymphocyte ratio in Guillain-Barre syndrome.
AB  - The purpose of this study was to investigate the prognostic value of the
      pretreatment and post-treatment albumin level, neutrophil-lymphocyte ratio (NLR),
      and platelet-lymphocyte ratio (PLR) in subtypes of Guillain-Barre syndrome (GBS).
      A retrospective analysis of 62 patients with GBS treated between 2011 and 2015 in
      Dicle University Hospital, Turkey, was carried out. The pretreatment and post
      treatment albumin, NLR, and PLR were documented, together with acute inflammatory
      demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, motor
      sensory axonal neuropathy, and Hughes' scores. Post-treatment albumin levels in
      GBS were significantly reduced, and albumin level was negatively correlated with
      the Hughes scores. Elevated pretreatment NLRs and PLRs were significantly
      associated with AIDP. There were no correlations between the Hughes scores, NLR,
      and PLR. The results point to a negative correlation between albumin levels and
      GBS disability and suggest that the NLR and PLR may be promising blood biomarkers
      of AIDP.

PMID- 27706421
TI  - Effects of crocin on brain oxidative damage and aversive memory in a 6-OHDA model
      of Parkinson's disease.
AB  - The purpose of the present study was to investigate the effect of crocin on brain
      oxidative damage and memory deficits in a 6-hydroxydopamine (6-OHDA) model of
      Parkinson's disease. Male Wistar rats were subjected to unilateral injection of 6
      OHDA (16 ug) into the medial forebrain bundle and treated with crocin (30 and 60
      mg/kg) for six weeks. The rats were tested for memory performance at six weeks
      after 6-OHDA infusion, and then were killed for the estimation of biochemical
      parameters. The increase in thiobarbituric acid reactive substances (TBARS) and
      nitrite levels in the hippocampus were observed in the 6-OHDA lesioned rats,
      which was accompanied by memory deficits in a passive avoidance test at the end
      of week 6. Moreover, treatment with crocin decreased TBARS and nitrite levels in
      the hippocampus, and improved aversive memory. The present study conclusively
      demonstrated that crocin acts as an antioxidant and anti-inflammatory agent in
      the hippocampus of parkinsonian rats and could improve aversive memory through
      its properties.

PMID- 27706422
TI  - Propentofylline reduces glial scar development following gliotoxic damage in the
      rat brainstem.
AB  - Objective: This study aimed to evaluate the effect of propentofylline
      administration on astrocytic response following gliotoxic injury. Method: Wistar
      rats were injected with ethidium bromide into the cisterna pontis and treated or
      not with propentofylline (12.5mg/kg/day, intraperitoneal) during the experimental
      period. Brainstem sections were collected from 15 to 31 days after gliotoxic
      injection and processed for GFAP immunohistochemistry. Results and Conclusion:
      Results demonstrate that propentofylline decreased astrocytic activation until
      the 21st day, suggesting that this drug may have a role in reducing glial scar
      development following injury.

PMID- 27706424
TI  - Surgical treatment of traumatic cervical facet dislocation: anterior, posterior
      or combined approaches?
AB  - Surgical treatment is well accepted for patients with traumatic cervical facet
      joint dislocations (CFD), but there is uncertainty over which approach is better:
      anterior, posterior or combined. We performed a systematic literature review to
      evaluate the indications for anterior and posterior approaches in the management
      of CFD. Anterior approaches can restore cervical lordosis, and cause less
      postoperative pain and less wound problems. Posterior approaches are useful for
      direct reduction of locked facet joints and provide stronger fixation from a
      biomechanical point of view. Combined approaches can be used in more complex
      cases. Although both anterior and posterior approaches can be used
      interchangeably, there are some patients who may benefit from one of them over
      the other, as discussed in this review. Surgeons who treat cervical spine trauma
      should be able to perform both procedures as well as combined approaches to
      adequately manage CFD and improve patients' final outcomes.

PMID- 27706423
TI  - Aged Lewis rats exposed to low and moderate doses of rotenone are a good model
      for studying the process of protein aggregation and its effects upon central
      nervous system cell physiology.
AB  - Cell physiology is impaired before protein aggregation and this may be more
      relevant than inclusions themselves for neurodegeneration. The present study
      aimed to characterize an animal model to enable the analysis of the cell biology
      before and after protein aggregation. Ten-month-old Lewis rats were exposed
      either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini
      pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta
      peptide and protein carbonylation (indicative of oxidative stress) were evaluated
      in the hippocampus, substantia nigra and locus coeruleus through
      immunohistochemistry or western blot. It was found that 2 mg/kg/day rotenone
      increased amyloid-beta peptide, hyperphosphorylation of TAU and alpha-synuclein.
      Rotenone at 1mg/kg/day did not alter protein levels. Protein carbonylation
      remained unchanged. This study demonstrated that aged Lewis rats exposed to a low
      dose of rotenone is a useful model to study cellular processes before protein
      aggregation, while the higher dose makes a good model to study the effects of
      protein inclusions.

PMID- 27706425
TI  - Clinical and genetic basis of congenital myasthenic syndromes.
AB  - Neuromuscular junction disorders represent a wide group of neurological diseases
      characterized by weakness, fatigability and variable degrees of appendicular,
      ocular and bulbar musculature involvement. Its main group of disorders includes
      autoimmune conditions, such as autoimmune acquired myasthenia gravis and Lambert
      Eaton syndrome. However, an important group of diseases include congenital
      myasthenic syndromes with a genetic and sometimes hereditary basis that resemble
      and mimick many of the classic myasthenia neurological manifestations, but also
      have different presentations, which makes them a complex clinical, therapeutic
      and diagnostic challenge for most clinicians. We conducted a wide review of
      congenital myasthenic syndromes in their clinical, genetic and therapeutic
      aspects.

PMID- 27706426
TI  - Abnormal eye movements in three types of chorea.
AB  - Chorea is an abnormal movement characterized by a continuous flow of random
      muscle contractions. This phenomenon has several causes, such as infectious and
      degenerative processes. Chorea results from basal ganglia dysfunction. As the
      control of the eye movements is related to the basal ganglia, it is expected,
      therefore, that is altered in diseases related to chorea. Sydenham's chorea,
      Huntington's disease and neuroacanthocytosis are described in this review as
      basal ganglia illnesses that can present with abnormal eye movements. Ocular
      changes resulting from dysfunction of the basal ganglia are apparent in saccade
      tasks, slow pursuit, setting a target and anti-saccade tasks. The purpose of this
      article is to review the main characteristics of eye motion in these three forms
      of chorea.

PMID- 27706427
TI  - Pain characterization in Duchenne muscular dystrophy.
AB  - Objective: To investigate the relationship between DMD and pain. Methods: We
      conducted a systematic review in Medline/PubMed and BVS (virtual library in
      health) databases. We searched for articles that showed the terms "Muscular
      Dystrophy, Duchenne" and "Pain" in all fields. All studies included boys
      diagnosed with DMD and the occurrence/amount of pain on this population. Results:
      Initially, there were 175 studies. 167 articles were excluded for not meeting the
      inclusion criteria. The remaining eight eligible studies, involving pain
      assessment in DMD, were analyzed. Conclusion: Pain is a frequent problem in this
      population and this symptom is potentially tractable. Studies conclude that pain
      can directly influence the quality of life of this population.

PMID- 27706428
TI  - Kraepelin's description of chronic mania: a clinical picture that meets the
      behavioral variant frontotemporal dementia phenotype.
AB  - Chronic mania is an under-investigated condition and few reports have associated
      this disorder with an organic background. The present work examines Kraepelin's
      reliable description of chronic mania from a current behavioral neurology
      viewpoint. Kraepelin had described a cluster of symptoms that are now recognized
      as core manifestations of the behavioral variant frontotemporal dementia (bvFTD)
      clinical phenotype. We also carried out additional reviews of original
      manuscripts from Kraepelin's peers, in order to find any case reports that might
      fulfill the current diagnostic proposal for bvFTD. Even though we failed to find
      an ideal case, we found some scholars who seemed to agree that chronic mania
      should be considered a special form of dementia. The present work highlights,
      through historical data, the possible overlapping features between primary
      psychiatric disorders and neuropsychiatric symptoms secondary to
      neurodegenerative conditions.

PMID- 27706429
TI  - A multi-country, cross-sectional observational study of retinopathy of
      prematurity in Latin America and the Caribbean.
AB  - Objective To consolidate available information from the Latin American and
      Caribbean (LAC) region on 1) national incidence of retinopathy of prematurity
      (ROP) and 2) national-level government inputs on ROP (existing national policies,
      guidelines, programs, and financing for ROP prevention, detection, and treatment,
      including ROP screening) in 2014. Methods In March and April 2015, a multi
      country online survey was distributed to 56 medical and public health experts
      working on ROP in LAC countries. Respondents were instructed to provide
      quantitative and qualitative information representative of the national situation
      in 2014 for ROP incidence and national-level government inputs (existing national
      policies, guidelines, programs, and financing for ROP prevention, detection, and
      treatment, including ROP screening) in their country. Results The survey was
      completed in full by a total of 11 experts from 10 LAC countries (Argentina,
      Brazil, Colombia, Costa Rica, Cuba, Dominican Republic, El Salvador, Mexico,
      Nicaragua, and Panama). According to the survey results, six countries had a
      national policy that includes ROP prevention, detection, and treatment, with
      screening and treatment covered by national/federal funding. Eight countries had
      national guidelines for ROP. Four countries had legislation mandating eye
      examination of preterm infants. Most countries had Level 3 and 4 neonatal
      intensive care units with ROP programs in public sector health care facilities.
      Five countries had a data collection or monitoring system to track the number of
      newborn babies screened for ROP within hospital settings. On average, countries
      with three or four of the above-mentioned ROP elements screened 95% of eligible
      newborns in 2014, while those with only one or two of the ROP elements screened
      35% of eligible newborns. Conclusions National government buy-in and involvement
      in ROP screening and treatment legislation is related to a higher proportion of
      eligible premature newborns being screened and treated for ROP. Further research
      should include more countries and assess national-level engagement with ROP,
      including ROP screening and treatment.

PMID- 27706430
TI  - ?

PMID- 27706431
TI  - Interventions that facilitate sustainable development by preventing toxic
      exposure to chemicals: an overview of systematic reviews.
AB  - Objective To identify interventions that 1) facilitate sustainable development by
      preventing toxic exposure to chemicals, including pesticides, and 2) have a
      positive impact on health. Methods This overview utilized systematic review
      methods to synthesize evidence from multiple systematic reviews and economic
      evaluations. A comprehensive search was conducted based on a predefined protocol,
      including clear inclusion criteria. To be classified as "sustainable"
      interventions needed to aim (explicitly or implicitly) to 1) have a positive
      impact on at least two key dimensions of the United Nations integrated framework
      for sustainable development and 2) include measures of health impact. Results
      Thirteen systematic reviews and two economic evaluations met the inclusion
      criteria. The interventions that were most likely to have a positive impact on
      health included 1) legislation to ban Endosulfan pesticide to prevent fatal
      poisonings; 2) testing of drinking water for contamination with arsenic, and
      dissemination of the results to households; and 3) implementation of organic
      farming / diet to reduce exposure to pesticides. However, the cost-effectiveness
      of these three interventions and their impact(s) on health inequalities is not
      known. Strict enforcement of interventions to reduce lead in houses with children
      was cost-beneficial. Education and dust control interventions performed by
      cleaning professionals to reduce blood lead levels in children were ineffective.
      Conclusions What is needed now is careful implementation of the interventions
      whose impacts are likely to be positive. Ineffective interventions need to be
      replaced with more effective and cost-effective interventions. Finally, more and
      better-quality research on the prevention of toxic exposure to chemicals is
      needed to better support policy development.

PMID- 27706432
TI  - [A fine line between legal and illegal oral drug repackaging].
AB  - In 2009, with the implementation of the National Hospital Pharmacy Model, Mexico
      began regulating single-dose drugs. The repackaging of oral drugs is fundamental
      and critical and should be standardized by Mexican health legislation to enable
      quality drugs to be dispensed. Data is required on stability, compatibility, drug
      interactions, containers, and repackaging methods, in order to establish a new
      expiration date. The literature on health regulations applicable to repackaging
      was analyzed, revealing major conceptual imprecisions since there is no
      legislation in Mexico that regulates repackaging; rather, everything is carried
      out according to pharmacists' recommendations and criteria. The conclusion is
      that the regulations need to be rewritten to establish minimum single-dose oral
      drug criteria for dispensing hospitals-regulations that cover infrastructure,
      equipment, and professionals complying with good practices in oral drug
      repackaging. A proposal is offered to implement an official Mexican standard that
      regulates single-dose repackaging and unifies concepts, criteria, and means of
      verification, while the pharmaceutical industry would be responsible for the
      technology and resources for single-dose drug packaging designed for the health
      sector.

PMID- 27706433
TI  - [Overview of regulatory aspects guiding tablet scoring].
AB  - Tablet scoring is a controversial but common practice used to adjust doses,
      facilitate drug intake, or lower the cost of drug treatment, especially in
      children and the elderly. The risks of tablet scoring are mainly related to
      inaccuracies in the resulting dose and stability problems. The aim of this
      article is to provide an overview of worldwide guidelines regarding tablet
      scoring. We found that regulatory health agencies in Mercosur countries as well
      as other South American countries do not have published standards addressing
      tablet splitting. Among the surveyed health agencies, the Food and Drug
      Administration (FDA) in the United States is the only one to present standards,
      ranging from splitting instructions to regulation of the manufacturing process.
      The concept of functional scoring implemented by the FDA has introduced some
      level of guarantee as to the ability of tablets to be split. In conclusion,
      technical and scientific bases are still insufficient to guide health rules on
      this subject, making the decision on scoring, in certain situations, random and
      highly risky to public health. The need for more detailed regulation is vital to
      ensure the safety of tablet medications.

PMID- 27706434
TI  - [Strategy for determining a baseline in areas of vector interruption for Chagas
      disease].
AB  - Objectives Present a strategy to determine the baseline in endemic areas in the
      process of vector interruption for Chagas disease (CHD). Methods A social and
      environmental questionnaire and an entomological survey evaluated the physical
      conditions of dwellings, the inhabitants' knowledge of CHD, the entomological
      triatomine indicators and the statistical relationship among these variables.
      Results Colonization and natural infection with Trypanosoma cruzi exist in
      Rhodnius prolixus, the principal vector of CHD in Colombia. Colonization was
      related to palm-thatched houses constructed with adobe or wattle and daub. The
      Panstrongylus geniculatus vector was found to be colonizing. Almost 50% of the
      surveyed population associated the term CHD with human disease and 37%, with
      triatomines. Conclusions R. prolixus can be considered to be the principal vector
      of T. cruzi in domestic environments and the process of interruption is feasible
      within the prioritized municipality. New studies are needed to verify the
      existence of wild populations of R. prolixus that could affect future stages of
      the process and demonstrate whether P. geniculatus is a factor in the
      transmission of T. cruzi. These scenarios can be made viable by including the
      inhabitants throughout the process, since they have been highly sensitive in
      vector detection inside their houses. The study design presented here can be
      adapted to other endemic areas of the Region of the Americas.

PMID- 27706435
TI  - [Validation of a questionnaire to evaluate administrative causes of low reporting
      of adverse drug reactions].
AB  - Objective Design and validate a survey to determine the administrative causes
      that can influence low reporting of adverse drug reactions. Methods The
      questionnaire design was based on a review of the literature and on
      brainstorming. The variables considered to influence reporting were professional
      workload and the professional perception of drug surveillance control activities.
      To validate the hypothesis, 60 professionals were surveyed in a convenience
      sample. Reliability was calculated using Cronbach's alfa and the Kuder-Richardson
      coefficient. Content validity was measured using the Kendall coefficient, and
      criterion validity, through concordance with the established criterion. Results
      The survey-type questionnaire was composed of 15 questions divided into two
      parts: general information and administrative causes of low adverse drug
      reactions reporting. Cronbach's alfa was 0.87, the Kuder-Richardson coefficient
      was 0.9033, and overall validity was 1.51, resulting from 70% concordance and a
      rank correlation coefficient of 0.81. Conclusions The reliability of the
      validated survey was acceptable to high and validity was acceptable.

PMID- 27706436
TI  - Health care factors associated with survival among women with breast cancer on
      hormone therapy in Rio de Janeiro, Brazil, 2004 - 2010.
AB  - Objectives To better understand the role that health care plays in breast cancer
      survival by investigating the effects that hormone therapy adherence and other
      select health care variables, adjusted for clinical and sociodemographic factors,
      had among a population of women in Rio de Janeiro, Brazil. Methods This was a
      longitudinal study based on secondary data of 5 861 women treated with hormone
      therapy (tamoxifen or aromatase inhibitors) at the National Cancer Institute of
      Brazil (INCA), from 1 January 2004 - 29 October 2010. Four different sources of
      data were integrated for analysis: INCA Pharmacy Sector Dispensation System;
      Hospital-based Cancer Registry; Integrated Hospital System and INCA Absolute
      System; and Mortality Information System. Analyses explored the effects of
      adherence to hormone therapy, disease care aspects, and sociodemographic,
      behavioral, and clinical variables, on the time of survival, using Kaplan-Meier
      and Cox proportional hazards models. Results The general survival rate was 94% in
      the first year after initiation of hormone therapy, and 71% in the fifth year.
      The Cox model indicated a higher hazard of death among women smokers, with more
      hospitalizations, more exams, and, among those who used, who used only aromatase
      inhibitors, as hormone therapy modality. The hazard was lower among women with a
      partner (stable relationship), a high school or college education a family
      history of cancer, and those who were treated by a mastologist, oncologist,
      and/or psychotherapist, who underwent surgery, and who adhered to hormone
      therapy. Conclusions The study indicated more vulnerable sub-groups and the
      aspects of care that provide best results, bringing new knowledge to improve
      assistance to this group of women.

PMID- 27706437
TI  - [Availability of indicators for monitoring the achievement of "Universal Health"
      in Latin America and the Caribbean].
AB  - Objective The objective of this study was to identify the availability of health
      indicators for validly measuring advances in the attainment of "universal health"
      in Latin America and the Caribbean (LAC). Methods A systematic search was
      undertaken for scientific evidence and available technical and scientific
      documents on assessing health system performance and advances in universal health
      in the following phases: phase 1, mapping of indicators; phase 2, classification
      of indicators; and phase 3, mapping the availability of selected indicators in
      LAC. Results Sixty-three (63) national sources of information and eight
      international sources were identified. A total of 749 indicators were selected
      from the different databases and studies evaluated, 619 of which were related to
      the attainment of universal health and 130 to the burden of disease. The
      following indicators were identified: financial protection, 42 (6%); coverage of
      service delivery, 415 (55.4%); population coverage, 6 (0.8%); health
      determinants, 101 (14%); assessment of inequalities in health, 55 (7.3%); and
      estimation of burden of disease, 130 (17.3%). Finally, the availability of 141
      indicators was mapped for each LAC country. Conclusions The results of this study
      will help establish a framework for measuring the achievements, obstacles, and
      rate of progress toward universal health in LAC.

PMID- 27706438
TI  - [Social impact of literacy in the household: analysis of the association with
      smoking in illiterate co-residents in Brazil].
AB  - Objective To investigate the social impact of literacy on the smoking behavior of
      illiterate individuals who share the household with literate individuals. Method
      This cross-sectional study employed data from the 2008 Brazilian National
      Household Survey (Pesquisa Nacional por Amostra de Domicilios, PNAD). Smokers
      were defined as individuals reporting use of any tobacco product daily or less
      than daily. The literacy profiles of residents were identified. Poisson
      regressions adjusted for skin color, age, and maximum level of literacy in the
      household were performed. Four groups were analyzed: men living in rural areas,
      men living in urban areas, women living in rural areas, and women living in urban
      areas. Results For urban men, the presence of literate women only in the
      household was a protection factor against smoking (prevalence ratio, PR: 0.77;
      95%CI: 0.71-0.82) vs. households in which all the males were illiterate. The same
      protective effect was found for rural men (PR: 0.79; 95%CI: 0.73-0.85). In turn,
      the presence of literate men only living in the same household with illiterate
      men did not provide protection against smoking in any case (PR: 0.93; 95%CI: 0.83
      1.03 for the urban subsample; and PR: 0.99; 95%CI: 0.88-1.11 for the rural
      subsample). Illiterate women benefited from the presence of both literate men
      (PR: 0.77; 95%CI: 0.71-0.84 for the urban sample; and PR: 0.78; 95%CI: 0.69-0.89
      for the rural subsample) and literate women (PR: 0.81; 95%CI: 0.72-0.92 for the
      urban subsample; and PR: 0.75; IC95%: 0.60-0.93 for the rural subsample).
      Conclusions Literate women seem to have positively affected illiterate co
      residents of both sexes. This result is in agreement with reports showing broad
      advantages of female schooling.

PMID- 27706440
TI  - Epistemological world awareness of healthcare faculty.
AB  - Objective: To understand how epistemological world awareness is expressed in the
      educational practices of healthcare professors. Methods: A qualitative,
      descriptive, exploratory, and analytical study. Data were collected through open
      end interviews and non-participant observation from May to December 2013, with 10
      professors from a public university in southern Brazil. The adopted theoretical
      framework was the composition of Paulo Freire and Lee Shulman. Data were analysed
      according to the operative proposal of Minayo. Results: The emerging category was
      Epistemological world awareness of healthcare professors. Conclusions: For
      professors to understand and reflect on the core knowledge categories required
      for their practice, they must have an epistemological world awareness that allows
      them to perceive themselves as unfinished in relation to the world and able to
      transform their practice.

PMID- 27706439
TI  - Swimming training attenuates oxidative damage and increases enzymatic but not non
      enzymatic antioxidant defenses in the rat brain.
AB  - Although it is well known that physical training ameliorates brain oxidative
      function after injuries by enhancing the levels of neurotrophic factors and
      oxidative status, there is little evidence addressing the influence of exercise
      training itself on brain oxidative damage and data is conflicting. This study
      investigated the effect of well-established swimming training protocol on lipid
      peroxidation and components of antioxidant system in the rat brain. Male Wistar
      rats were randomized into trained (5 days/week, 8 weeks, 30 min; n=8) and non
      trained (n=7) groups. Forty-eight hours after the last session of exercise,
      animals were euthanized and the brain was collected for oxidative stress
      analysis. Swimming training decreased thiobarbituric acid reactive substances
      (TBARS) levels (P<0.05) and increased the activity of the antioxidant enzyme
      superoxide dismutase (SOD) (P<0.05) with no effect on brain non-enzymatic total
      antioxidant capacity, estimated by FRAP (ferric-reducing antioxidant power) assay
      (P>0.05). Moreover, the swimming training promoted metabolic adaptations, such as
      increased maximal workload capacity (P<0.05) and maintenance of body weight. In
      this context, the reduced TBARS content and increased SOD antioxidant activity
      induced by 8 weeks of swimming training are key factors in promoting brain
      resistance. In conclusion, swimming training attenuated oxidative damage and
      increased enzymatic antioxidant but not non-enzymatic status in the rat brain.

PMID- 27706441
TI  - Assessing nursing diagnoses and interventions in labour and high-risk
      pregnancies.
AB  - Objective: To evaluate the use of nursing diagnoses and interventions proposed
      for women in labour and high-risk pregnancies. Method: This is a descriptive,
      retrospective study with documentary analysis of 1000 medical records and a
      checklist conducted from July to September 2014, at a maternity hospital in
      Paraiba, Brazil. It consisted of analysing descriptive measures and comparing the
      relationship between nursing diagnoses and interventions using NANDA -
      International and the Nursing Interventions Classification. Results: The most
      common diagnoses in labour were acute pain (62%), fatigue (24.7%), and anxiety
      (22%). For high-risk pregnant women they were impaired sleep and rest (100%),
      risk of infection (81.8%), and anxiety (77.2%). The interventions were hand
      washing (80.8%) and identify and accommodate patient in the bed (78%).
      Conclusion: The diagnoses express needs during parturition and the
      psychobiological changes in high-risk pregnancy. The interventions are
      disconnected from the diagnoses and should therefore be reviewed and altered.

PMID- 27706442
TI  - Women waste pickers: living conditions, work, and health.
AB  - Objective: To know the elements of work, health, and living conditions of women
      who pick recyclable waste and are members of a waste cooperative in a town of the
      state of Rio Grande do Sul, Brazil. Method: This is a qualitative, exploratory
      and descriptive study with seven subjects. Data were collected through
      participative observation, semi structured interview, and a focus group from July
      to August of 2013. The data were subjected to content analysis. Results: The
      following thematic categories emerged: Women's work, informality and
      precariousness; Experiences of job satisfaction; and Working conditions and
      health: experiences with accidents, illness and health services. Conclusion: It
      was concluded that the women who collect recyclable material are exposed to
      precarious work conditions and potential health risks, such as work overload,
      accidents, illness, and social insecurity, and that nurses are responsible for
      promoting actions that ensure the health and inclusion of these workers.

PMID- 27706443
TI  - Social determinants of health and quality of life of caregivers of children with
      cancer.
AB  - Objective: to associate the social determinants of health and quality of life of
      caregivers of children with cancer. Methods: a cross-sectional study conducted in
      a paediatric cancer centre in Fortaleza, Brazil, with 176 participants in
      November and December 2013. Data were collected using a questionnaire with social
      determinants of health, and quality of life was assessed using the World Health
      Organization Quality of Life-Bref. The determinants were correlated with the
      averages of the quality of life domains using analysis of variance (ANOVA).
      Results: there was a statistically significant association between the domains of
      social relations and education (p = 0.01792) and between the psychosocial domain
      and the gender of the caregiver (p = 0.01901). The male caregivers that were
      highly educated, younger, married, stay-at-home dads from the interior had a
      better quality of life. Conclusion: the study sheds light on the influence of
      social determinants of health in the quality of life of caregivers of children
      with cancer.

PMID- 27706444
TI  - Model of transpersonal caring in nursing home care according to Favero and
      Lacerda: case report.
AB  - Objective: The aim of this paper is to report the experiences of applying a model
      of transpersonal caring in nursing home care according to Favero and Lacerda to
      adult patients after hematopoietic stem cell transplantation. Method: This is a
      case report on the application of this model to an outpatient monitored by a bone
      marrow transplant service. In addition to the initial outpatient contact, the
      patient received home care visits in October 2014. Data were recorded in the
      field diary and analysed according to the Care Model and Clinical Caritas
      Process. Results: The provided care served as support to meet basic human needs,
      and strengthen the belief system. It also promoted the necessary emotional care
      to cope with the treatment and professional maturity in the caring relationship.
      Conclusion: The experience description revealed that the model can support the
      application of the Theory of Human Caring in home care and the use of care models
      in practice, professional training, and research development.

PMID- 27706445
TI  - Defense strategies in the nursing work environment of long-stay institutions for
      the elderly.
AB  - Objective: To describe the defense strategies used by nurses working in long-stay
      institutions for the elderly when faced with work environment distress.
      Methodology: Descriptive, exploratory and qualitative research performed through
      interviews held with 27 nurses at long-stay institutions for the elderly between
      April and September 2013. Data analysis was performed through content analysis
      and the theory known as work psychodynamics. Results: The strategies used were:
      considering death as something natural, understanding death of those in critical
      condition as the end to a sufferable condition, understanding the patient's
      resistance as a symptom of disease and senility, limit the reach of work problems
      in their personal life, and restrict the affective involvement with patients.
      Conclusion: The nursing professionals indicated the development of individual
      defense strategies - grouped as protection, adaptation and exploitation measures 
      in order to deal with situations that generate distress in their work
      environment.

PMID- 27706446
TI  - Infantile autism: impact of diagnosis and repercussions in family relationships.
AB  - Objective: To analyse the context in which the diagnosis of autism is revealed
      and the impact of this revelation on family relationships. Methods: This is a
      qualitative study with 10 families of autistic children assisted at the
      Psychosocial Care Centre for Children and Youths in a municipality of Paraiba.
      Data were collected between July and August 2013 through semi-structured
      interviews and interpreted using thematic content analysis. Results: The
      identified Main Unit of Analysis and the respective categories were: the impact
      of disclosing the diagnosis of autism to the family; characteristics of diagnosis
      disclosure: the place, time, and the dialogic relationship between the
      professional and the family; changes in family relationships and the mother's
      burden when caring for the autistic child. Conclusions: The health professionals
      who report autism should better prepare the family to cope with the difficulties
      of this syndrome and autonomously care for the autistic child.

PMID- 27706447
TI  - Application of software in qualitative research.

PMID- 27706448
TI  - DRUG RESISTANCE IN HELICOBACTER PYLORI.

PMID- 27706449
TI  - DRUG RESISTANCE IN HELICOBACTER PYLORI.
AB  - Background: Helicobacter pylori has a worldwide distribution and is associated
      with the pathogenesis of various diseases of the digestive system. Treatment to
      eradicate this microorganism involves the use of a combination of antimicrobials,
      such as amoxicillin, metronidazole, clarithromycin, and levofloxacin, combined
      with proton pump inhibitors. Although the current therapy is effective, a high
      rate of treatment failure has been observed, mainly because of the acquisition of
      point mutations, one of the major resistance mechanisms developed by H. pylori.
      This phenomenon is related to frequent and/or inappropriate use of antibiotics.
      Conclusion: This review reported an overview of the resistance to the main drugs
      used in the treatment of H. pylori, confirming the hypothesis that antibacterial
      resistance is a highly local phenomenon and genetic characteristics of a given
      population can influence which therapy is the most appropriate.

PMID- 27706450
TI  - IS THE IMMUNOCROMATOGRAPHIC FECAL ANTIGEN TEST EFFECTIVE FOR PRIMARY DIAGNOSIS OF
      HELICOBACTER PYLORI INFECTION IN DYSPEPTIC PATIENTS?
AB  - Background: The diagnosis of H. pylori infection can be performed by non-invasive
      and invasive methods.The identification through a fecal antigen test is a non
      invasive, simple, and relatively inexpensive test. Objective: To determine the
      diagnostic performance of fecal antigen test in the identification of H. pylori
      infection. Methods: H. pylori antigens were identified in the stools of dyspeptic
      patients undergoing upper gastrointestinal endoscopy. For the identification of
      H. pylori antigen, we use ImmunoCard STAT! HpSA with immunochromatography
      technique. Histopathology plus urease test were the gold standard. Results: We
      studied 163 patients, 51% male, mean age of 56.7+/- 8.5years. H. pylori infection
      was present in 49%. Fecal test presented: sensitivity 67.5% (CI95% 60.6-72.9);
      specificity 85.5% (CI95% 78.9-90.7); positive predictive value 81.8% (CI95% 73.4
      88.4) and negative predictive value 73,2% (CI95% 67.5-77.6); Positive likelihood
      ratio was 4.7 (CI95% 2.9-7.9) and Negative Likelihood Ratio 0.4 (CI95% 0.3-0.5).
      The prevalence odds ratio for a positive test was 12.3 (CI95% 5.7-26.3).The index
      kappa between FAT and histology/urease test was 0.53 (CI95% 0.39-0.64).
      Conclusion: Immunochromatographic FAT is less expensive than the other methods
      and readily accepted by the patients but its diagnostic performance does not
      recommend its use in the primary diagnosis, when the patient may have an active
      infection.

PMID- 27706452
TI  - EARLY AND LATE ASSESSMENT OF ESOPHAGOCARDIOPLASTY IN THE SURGICAL TREATMENT OF
      ADVANCED RECURRENT MEGAESOPHAGUS.
AB  - Background: Since Chagas disease has esophageal manifestations with different
      degrees of involvement, the best surgical option is controversial, especially for
      patients with advanced chagasic megaesophagus and recurrent symptoms after
      previous treatment. Objective: To assess the early and late outcomes of
      esophagocardioplasty in a series of patients with advanced recurrent chagasic
      megaesophagus. Methods: This descriptive study included 19 older patients with
      recurrent megaesophagus grade III/IV and positive immunofluorescence for Chagas
      disease. They had undergone cardiomyotomy with anterior fundoplication a mean of
      16.5 years ago. Serra-Doria esophagocardioplasty was selected to treat the
      recurrence. The patients were followed to assess postoperative and late
      complications and the incidence of symptom recurrence. Results: In early
      assessment, five (26.3%) patients presented clinical complications. One (5.2%)
      patient had a gastrointestinal fistula secondary to esophagogastric anastomotic
      leak, which responded well to conservative treatment. In the one-year follow-up,
      18 (94.7%) patients could swallow normally and had no vomiting. Three years after
      surgery, 10 (62.5%) of 16 patients could swallow normally, and 3 (19.3%) patients
      complained of vomiting. Five years after surgery, only 5 (38.4%) of 13 patients
      could swallow normally and 7 (53.8%) had vomiting. Conclusion: Serra-Doria
      esophagocardioplasty for the treatment of advanced recurrent megaesophagus had
      mild postoperative complications and good success rate in the short-term follow
      up. In the long-term follow-up, it proved to be a poor surgery choice because of
      the high incidence of symptom recurrence, compromising quality of life. This
      procedure should be indicated only for patients with advanced recurrent
      megaesophagus without clinical conditions to undergo esophageal resection.

PMID- 27706451
TI  - ORAL ADMINISTRATION OF EXOGENOUS LACTASE IN TABLETS FOR PATIENTS DIAGNOSED WITH
      LACTOSE INTOLERANCE DUE TO PRIMARY HYPOLACTASIA.
AB  - Background: Primary hypolactasia is a common condition where a reduced lactase
      activity in the intestinal mucosa is present. The presence of abdominal symptoms
      due to poor absorption of lactose, which are present in some cases, is a
      characteristic of lactose intolerance. Objective: Evaluate the efficacy of a
      product containing exogenous lactase in tablet form compared to a reference
      product with proven effectiveness in patients with lactose intolerance. Methods:
      Multicentre, randomized, parallel group, single-blind, comparative non
      inferiority study. One hundred twenty-nine (129) adult lactose intolerance
      patients with hydrogen breath test results consistent with a diagnosis of
      hypolactasia were randomly assigned to receive the experimental product
      (Perlatte(r) - Eurofarma Laboratorios S.A.) or the reference product (Lactaid(r) 
      McNeilNutritionals, USA) orally (one tablet, three times per day) for 42
      consecutive days. Results: Data from 128 patients who actually received the
      studied treatments were analysed (66 were treated with the experimental product
      and 62 with the reference product). The two groups presented with similar
      baseline clinical and demographic data. Mean exhaled hydrogen concentration
      tested at 90 minutes after the last treatment (Day 42) was significantly lower in
      the experimental product treated group (17+/-18 ppm versus 34+/-47 ppm) in the
      per protocol population. The difference between the means of the two groups was 
      17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the
      95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary
      efficacy analyses confirmed that the treatments were similar (per protocol and
      intention to treat population). The tolerability was excellent in both groups,
      and there were no reports of serious adverse events related to the study
      treatment. Conclusion: The experimental product was non-inferior to the reference
      product, indicating that it was an effective replacement therapy for endogenous
      lactase in lactose intolerance patients.

PMID- 27706453
TI  - IS DIGITAL RECTAL EXAM RELIABLE IN GRADING ANAL SPHINCTER DEFECTS?
AB  - Background: Anal sphincter tone is routinely assessed by digital rectal
      examination in patients with fecal incontinence, although its accuracy in
      detecting sphincter defects or separating competent from incompetent muscles has
      not been established. Objective: In this setting, we aimed to evaluate the
      accuracy of digital rectal examination in grading anal defects in order to
      separate small from extensive cases as depicted on 3D endoanal ultrasound, using
      a scoring sphincter defect and correlate anal tone to anal pressures. Methods:
      Women with fecal incontinence were divided into two groups: small or extensive
      defects according to the ultrasound scoring system. Sensitivity, specificity,
      positive and negative predictive values of digital rectal examination in grading
      global and external sphincter defects were calculated. Anal tone at digital
      rectal examination was compared to resting and incremental pressures. Results: A
      cohort of 76 consecutive incontinent women were enrolled. The median Wexner score
      was 9. Sixty-eight showed sphincter defects on 3D endoanal ultrasound. Anal tone
      at digital rectal examination was considered abnormal in 62 cases. Abnormal
      digital rectal examination showed a sensitivity of 90%, specificity of 27.78% in
      distinguishing small from extensive defects of both sphincters. Five out of eight
      women with no sphincter defects had only abnormal squeeze tone at digital rectal
      examination. Abnormal squeeze tone at digital rectal examination had a
      sensitivity of 65.31% in distinguishing small from extensive external anal
      sphincter defects. Digital rectal examination sensitivity increased linearly from
      small to extensive external anal sphincter defects (P=0.001). Women with abnormal
      resting tone had lower resting pressures than women with normal tone at digital
      rectal examination (P=0.0001). Women with abnormal squeeze tone had lower
      incremental pressures than women with normal tone at digital rectal examination
      (P=0.017). Conclusion: Digital rectal examination had good sensitivity and poor
      specificity in discerning small from severe global anal sphincter defects.
      Moreover, digital rectal examination had fair sensitivity and poor specificity in
      grading external anal sphincter defects, and its best accuracy was on complete
      external anal sphincter lesions. Anal resting and squeeze tone were correlated to
      anal pressures.

PMID- 27706454
TI  - FREQUENCY OF THE MDR1 GENE POLYMORPHISM RS1045642 (C3435T) IN HCV-HIV CO-INFECTED
      PATIENTS.
AB  - Background: Due to the high prevalence of co-infection by hepatitis C virus (HCV)
      and human immunodeficiency virus (HIV) and the severity of these infections, the
      understanding of the biological mechanisms involved in these processes, including
      viral behavior and host genetic profile, is of great importance for patient
      treatment and for public health policies.Some single nucleotide polymorphisms
      (SNPs) in the human genome, such as the SNP rs1045642 (C3435T) in the MDR1 gene,
      have been reported to be associated to the sustained virological response (SVR)
      to HCV treatment in HCV-HIV co-infected patients. Objective: The present study
      analyzes the MDR1 gene C3435T polymorphism in HCV-HIV co-infected patients.
      Methods: A total of 99 HCV-HIV patients were included in the study. The DNA was
      extracted from blood samples, and the SNP rs1045642 was assessed by Real Time PCR
      (qPCR). Risk factors for acquiring the virus and the SVR after HCV treatment with
      pegylated interferon-alpha and ribavirin were also analyzed. Results: Among the
      patients, 54 (54.5%) were male and 45 (45.5%) were female. The average age was
      46.1+/-9.8 years. The SVR after HCV treatment was 40%. The frequencies of MDR1
      genotypes CC, CT and TT were 28.3%, 47.5% and 24.2%, respectively. Allele
      frequencies were 52% for the C allele and 48% for the T allele. No association
      was found for SNP rs1045642 (C3435T) regarding response to treatment (P=0.308).
      Conclusion: - In this study, the C3435T polymorphism in the MDR1 gene appears not
      to be associated with SVR in HCV-HIV co-infected individuals.

PMID- 27706455
TI  - FOOD CONSUMPTION OF CIRRHOTIC PATIENTS, COMPARISON WITH THE NUTRITIONAL STATUS
      AND DISEASE STAGING.
AB  - Background: Patients with liver disease often present protein-energy
      malnutrition. The assessment of food intake is very important in the
      investigation regarding the "health-disease" process. Objective: To assess
      dietary intake of cirrhotic patients through food record during 3 days,
      correlating it with the nutritional status of the patient and the stage of the
      disease. Methods: Cirrhotic outpatients from the Santa Casa de Misericordia
      Hospital, RS, Brazil, were assessed. Nutritional assessment was performed by
      anthropometry; non-dominating handgrip strength; adductor pollicis muscle
      thickness; phase angle by bioelectrical impedance analysis; and Subjective Global
      Assessment. For analysis of food consumption we used the food records of 3 days
      using scales for weighing of all foods. Results: We evaluated 25 (68%) patients,
      in which there was a prevalence of cirrhosis by hepatitis C virus. The upper arm
      circumference, handgrip strength and phase angle by bioelectrical impedance
      analysis diagnosed 56% of malnourished. Phase angle by bioelectrical impedance
      analysis and upper arm circumference were associated with Child-Pugh score
      (P<0.05). The average consumption of calories, carbohydrates, proteins and lipids
      were within the recommended. However, sodium was above the recommendations, 106+/
      57.2 mEq, and was inversely associated with Child-Pugh score (rs=-0.410;
      P=0.042). Conclusion: Food intake did not have a significant difference between
      the Child-Pugh scores and nutritional status. In addition, food intake did not
      vary neither according to the stage of the disease, nor to the nutritional
      assessment, by the phase angle by bioelectrical impedance analysis.

PMID- 27706456
TI  - EVALUATION OF PRIMARY PROPHYLAXIS WITH PROPRANOLOL AND ELASTIC BAND LIGATION IN
      VARICEAL BLEEDING IN CIRRHOTIC CHILDREN AND ADOLESCENTS.
AB  - Background: The efficacy of nonselective beta-blocker and endoscopic procedures,
      such as endoscopic variceal ligation, as primary prophylaxis of variceal
      hemorrhage in cirrhotic adults was demonstrated by numerous controlled trials,
      but in pediatric population, few are the number of studies. Objective: The
      objective of this study is to evaluate the primary prophylaxis with beta-blocker
      in cirrhotic children and adolescents with portal hypertension. Methods: This is
      a cohort study encompassing 26 cirrhotic patients. beta-blocker prophylaxis was
      performed with propranolol. When contraindicated the use of beta-blocker, or if
      side effects presents, the patients were referred to endoscopic therapy with band
      ligation. Patients were evaluated by endoscopy, and those who had varicose veins
      of medium and large caliber or reddish spots, regardless of the caliber of
      varices, received primary prophylaxis. Results: Of the 26 patients evaluated, 9
      (34.6%) had contraindications to the use of propranolol and were referred for
      endoscopic prophylaxis. Six (35.3%) of the 17 patients who received beta-blocker
      (propranolol), had bled after a median follow-up time of 1.9 years. beta-blockage
      dosage varied from 1 mg/kg/day to 3.1 mg/kg/day and seven (41.2%) patients had
      the propranolol suspended due to fail of the beta-blockage or adverse effects,
      such as drowsiness, bronchospasm and hypotension. Patients who received
      endoscopic prophylaxis (elastic bandage) had no bleeding during the follow-up
      period. Conclusion: All of the patients that had upper gastroinstestinal bleeding
      in this study were under propranolol prophylaxis. The use of propranolol showed a
      high number of contraindications and side effects, requiring referral to
      endoscopic prophylaxis. The endoscopic prophylaxis was effective in reducing
      episodes of bleeding.

PMID- 27706457
TI  - ALLERGIC PROCTOCOLITIS IN INFANTS: analysis of the evolution of the nutritional
      status.
AB  - Background: Allergic proctocolitis is a disease that affects infants in the first
      months. The change in feed is the primary factor for clinical improvement and
      maintenance of the nutritional status of the infant. Objective: Study the
      anthropometric evolution of infants with allergic proctocolitis at diagnosis and
      1 to 6 months after nutritional intervention. Methods: A retrospective cohort of
      infants with allergic proctocolitis diagnosis followed at the Pediatric
      Gastroenterology Institute of Sao Paulo (IGASTROPED), Brazil. The database with
      clinical, therapeutic and anthropometric data was obtained from medical records
      of outpatient infants. The therapeutic intervention was characterized by 1)
      exclusive breastfeeding with maternal exclusion diet of the six allergens (EBF
      MED) or 2) no breastfeeding and use of hypoallergenic formulas. Results: Of the
      44 infants diagnosed with allergic proctocolitis, 23 were female. The median age
      of the infants was 3.5 months at the time of admission and 6 months after the
      intervention. The main clinical complaint was hematochezia with or without other
      symptoms of allergic proctocolitis. No difference was shown in the infants
      anthropometric evaluation between the two diets. Conclusion: The duration of the
      allergic proctocolitis did not induce worsening of the infants nutritional
      status. Importantly, both nutritional interventions were able to keep the infants
      within the growth channel and resulted in the total clinical symptoms remission.
      Considering the fundamental mother-child link promoted by breastfeeding, the
      present data highlights the beneficial role of EBF-MED on the nutritional status
      of infants diagnosed with allergic proctocolitis in addition to the lower cost
      that breastfeeding brings compared the use of hypoallergenic formulas.

PMID- 27706458
TI  - PREVALENCE OF GENETIC SUSCEPTIBILITY FOR CELIAC DISEASE IN BLOOD DONORS IN SAO
      PAULO, BRAZIL.
AB  - Background: Celiac disease is a permanent intolerance induced by gluten, which is
      expressed by T-cell mediated enteropathy, and has a high prevalence in the
      general population. There is evidence of a strong genetic predisposition to
      celiac disease. Objective: To determine the prevalence of genetic markers HLA-DQ2
      and HLA-DQ8 in blood donors from Sao Paulo and measure human recombinant tissue
      transglutaminase antibody IgA class in HLA-DQ2 and HLA-DQ8 positive donors.
      Methods: A total of 404 blood donors from Sao Paulo city and Jundiai were
      included in the study and signed the informed consent form. Information regarding
      diarrhea, constipation and abdominal pain in the last 3 months was collected.
      Determination of HLADQ2 and HLADQ8 alleles was performed in all participants and
      human recombinant tissue transglutaminase antibody class IgA was measured only in
      blood donors who presentedDQ2 and/or DQ8. Results: HLADQ2 and/or HLADQ8 were
      positive in 49% (198/404) of subjects. Positive samples were associated with
      alleles DR3, DR4, DR7, DR11 and DR12. The most frequent genotype was DR4-DQ8,
      which was present in 13.6% of samples, followed by genotypes DR3-DQ2 and DR7-DQ2
      with DQB1*02 in heterozygous, which were present in 10.4% and 8.7%, respectively.
      Eleven out of 198 positive donors (5%) were positive to human tissue
      transglutaminase test. Conclusion: We observed a high prevalence of genetic
      markers for celiac disease, HLA-DQ2 and HLA-DQ8, in blood donors from Sao Paulo,
      similar to prevalence described in Europe. These findings show that the
      prevalence of celiac disease should not be rare in our country, but
      underdiagnosed.

PMID- 27706459
TI  - LONG-TERM POSTOPERATIVE ENDOSCOPIC FINDINGS AFTER GASTRIC BYPASS PROCEDURE: a co
      occurrence analysis.
AB  - Background: A multitude of endoscopic findings post-gastric bypass procedures
      have been previously reported in the literature, but to our knowledge, no present
      rules exist that could guide clinicians regarding which findings should be
      actively sought, once an initial finding is identified. Objective: To identify co
      occurrence patterns among endoscopic findings of patients having undergone past
      gastric bypass procedure. Methods: Our registry involves all consecutive patients
      undergoing an upper endoscopic evaluation after a gastric bypass procedure. We
      collected information on the presence of the endoscopic findings in post-gastric
      bypass surgery patients. Co-occurrence evaluation involved the use of
      intersection, cluster and item factor analyses. Results: A total of 396
      endoscopic evaluations were made on 339 patients. Most patients were female
      (81.1%), with an average BMI of 31.88+/-6.7 at the time of endoscopy. Esophagitis
      was the most common isolated finding (35.3%). Endoscopic findings clustered
      around two groups, (1) the ring-related complications involving ring
      displacement, ring slips and gastric pouch, while (2) stenosis-related findings
      involved dilation and stenosis (P<0.01). Conclusion: While most endoscopic
      findings after gastric bypass endoscopic procedures are isolated, ring and
      stenosis-related clusters should be used as a set of rules by clinicians, as it
      might enhance their probability of finding co-occurring conditions.

PMID- 27706461
TI  - Erratum.
AB  - [This corrects the article doi: 10.1590/S0004-28032016000300001].

PMID- 27706460
TI  - ALTERATION OF TASTE BUDS IN EXPERIMENTAL CIRRHOSIS. Is there correlation with
      human hypogeusia?
AB  - Background: The inherent complications of cirrhosis include protein-calorie
      malnutrition and micronutrient deficiencies.Changes in taste are detrimental to
      the nutritional status, and the mechanism to explain these changes is not well
      documented in the cirrhotic patients. Objective: To evaluate the taste buds of
      cirrhotic rats. Methods: Fourteen male Wistar rats were evaluated. After 16
      weeks, the liver was removed to histologically diagnose cirrhosis, and blood was
      collected to perform liver integrity tests. The tongue was removed for
      histological examination and immunohistochemistry using antibodies against
      protein gene product PGP 9.5 and the sweet taste receptors T1R2 and T1R3.
      Morphological changes were determined by scanning electron microscopy. Serum zinc
      levels were measured. Results: The cirrhotic animals, but not the control
      animals, exhibited zinc deficiency. In both groups, there was positive
      immunoreactivity for type II and III cells and T1R2 receptors. The cirrhotic
      animals had no immunoreactivity for T1R3 receptors. Scanning electron microscopy
      analysis of the cirrhotic group revealed a uniform tapering of the gustatory
      papillae. Conclusion: In conclusion the experimental cirrhosis model mimicked the
      biochemical and histological parameters of human cirrhosis, therefore enabling a
      study of the gustatory papillae and taste buds.

PMID- 27706462
TI  - Effectiveness of prophylactic non-invasive ventilation on respiratory function in
      the postoperative phase of pediatric cardiac surgery: a randomized controlled
      trial.
AB  - Objective: To evaluate the effectiveness of prophylactic, non-invasive
      ventilation (NIV) on respiratory function in seven- to 16-year-old children in
      the post-operative phase of cardiac surgery. Method: A randomized, controlled
      trial with 50 children who had undergone cardiac surgery with median sternotomy.
      After extubation, patients were randomly assigned to one of two groups: control
      group (n=26), which received instructions regarding posture, early ambulation,
      and cough stimulation, and CPAP group (continuous positive airway pressure;
      n=24), which received the same instructions as the control group and CPAP=10
      cmH20 twice daily for 30 minutes from the 1st to the 5th post-operative day
      (POD). As a primary outcome, lung function was evaluated before and on the 1st,
      3rd, and 5th PODs with measures of respiratory rate (RR), tidal volume (TV), slow
      vital capacity (SVC), inspiratory capacity (IC), minute volume (MV), peak
      expiratory flow (PEF), and maximal inspiratory pressure (MIP). As secondary
      outcomes, the time of hospitalization and intensive care were recorded. A mixed,
      linear regression model and z-test were used to analyze respiratory function,
      considering p<0.05. Results: All variables, except RR and MV, showed a
      significant drop on the 1st POD, with gradual recovery; however, only MIP had
      returned to pre-operative values on the 5th POD in both groups. The RR showed a
      significant increase on the 1st POD, with a gradual reduction but without
      returning to baseline. In the intergroup analysis, significant improvement
      (p=0.04) was observed only in PEF in the CPAP group on the 1st DPO. The length of
      hospitalization and intensive care showed no significant differences. Conclusion:
      NIV was safe and well accepted in this group of patients, and the protocol used
      was effective in improving PEF on the 1st DPO in the CPAP group.

PMID- 27706463
TI  - Empirical Antifungal Therapy in Critically Ill Patients With Sepsis: Another Case
      of Less Is More in the ICU.

PMID- 27706464
TI  - Effect of Postextubation High-Flow Nasal Cannula vs Noninvasive Ventilation on
      Reintubation and Postextubation Respiratory Failure in High-Risk Patients: A
      Randomized Clinical Trial.
AB  - Importance: High-flow conditioned oxygen therapy delivered through nasal cannulae
      and noninvasive mechanical ventilation (NIV) may reduce the need for
      reintubation. Among the advantages of high-flow oxygen therapy are comfort,
      availability, lower costs, and additional physiopathological mechanisms.
      Objective: To test if high-flow conditioned oxygen therapy is noninferior to NIV
      for preventing postextubation respiratory failure and reintubation in patients at
      high risk of reintubation. Design, Setting, and Participants: Multicenter
      randomized clinical trial in 3 intensive care units in Spain (September 2012
      October 2014) including critically ill patients ready for planned extubation with
      at least 1 of the following high-risk factors for reintubation: older than 65
      years; Acute Physiology and Chronic Health Evaluation II score higher than 12
      points on extubation day; body mass index higher than 30; inadequate secretions
      management; difficult or prolonged weaning; more than 1 comorbidity; heart
      failure as primary indication for mechanical ventilation; moderate to severe
      chronic obstructive pulmonary disease; airway patency problems; or prolonged
      mechanical ventilation. Interventions: Patients were randomized to undergo either
      high-flow conditioned oxygen therapy or NIV for 24 hours after extubation. Main
      Outcomes and Measures: Primary outcomes were reintubation and postextubation
      respiratory failure within 72 hours. Noninferiority margin was 10 percentage
      points. Secondary outcomes included respiratory infection, sepsis, and multiple
      organ failure, length of stay and mortality; adverse events; and time to
      reintubation. Results: Of 604 patients (mean age, 65 [SD, 16] years; 388 [64%]
      men), 314 received NIV and 290 high-flow oxygen. Sixty-six patients (22.8%) in
      the high-flow group vs 60 (19.1%) in the NIV group were reintubation (absolute
      difference, -3.7%; 95% CI, -9.1% to infinity); 78 patients (26.9%) in the high
      flow group vs 125 (39.8%) in the NIV group experienced postextubation respiratory
      failure (risk difference, 12.9%; 95% CI, 6.6% to infinity) [corrected]. Median
      time to reintubation did not significantly differ: 26.5 hours (IQR, 14-39 hours)
      in the high-flow group vs 21.5 hours (IQR, 10-47 hours) in the NIV group
      (absolute difference, -5 hours; 95% CI, -34 to 24 hours). Median
      postrandomization ICU length of stay was lower in the high-flow group, 3 days
      (IQR, 2-7) vs 4 days (IQR, 2-9; P=.048). Other secondary outcomes were similar in
      the 2 groups. Adverse effects requiring withdrawal of the therapy were observed
      in none of patients in the high-flow group vs 42.9% patients in the NIV group (P
      < .001). Conclusions and Relevance: Among high-risk adults who have undergone
      extubation, high-flow conditioned oxygen therapy was not inferior to NIV for
      preventing reintubation and postextubation respiratory failure. High-flow
      conditioned oxygen therapy may offer advantages for these patients. Trial
      Registration: clinicaltrials.gov Identifier: NCT01191489.

PMID- 27706465
TI  - Same-Day Discharge After Percutaneous Coronary Intervention-Reply.

PMID- 27706466
TI  - Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients
      in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial.
AB  - Importance: Despite suggestions of potential harm from unnecessary oxygen
      therapy, critically ill patients spend substantial periods in a hyperoxemic
      state. A strategy of controlled arterial oxygenation is thus rational but has not
      been validated in clinical practice. Objective: To assess whether a conservative
      protocol for oxygen supplementation could improve outcomes in patients admitted
      to intensive care units (ICUs). Design, Setting, and Patients: Oxygen-ICU was a
      single-center, open-label, randomized clinical trial conducted from March 2010 to
      October 2012 that included all adults admitted with an expected length of stay of
      72 hours or longer to the medical-surgical ICU of Modena University Hospital,
      Italy. The originally planned sample size was 660 patients, but the study was
      stopped early due to difficulties in enrollment after inclusion of 480 patients.
      Interventions: Patients were randomly assigned to receive oxygen therapy to
      maintain Pao2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation
      (Spo2) between 94% and 98% (conservative group) or, according to standard ICU
      practice, to allow Pao2 values up to 150 mm Hg or Spo2 values between 97% and
      100% (conventional control group). Main Outcomes and Measures: The primary
      outcome was ICU mortality. Secondary outcomes included occurrence of new organ
      failure and infection 48 hours or more after ICU admission. Results: A total of
      434 patients (median age, 64 years; 188 [43.3%] women) received conventional (n =
      218) or conservative (n = 216) oxygen therapy and were included in the modified
      intent-to-treat analysis. Daily time-weighted Pao2 averages during the ICU stay
      were significantly higher (P < .001) in the conventional group (median Pao2, 102
      mm Hg [interquartile range, 88-116]) vs the conservative group (median Pao2, 87
      mm Hg [interquartile range, 79-97]). Twenty-five patients in the conservative
      oxygen therapy group (11.6%) and 44 in the conventional oxygen therapy group
      (20.2%) died during their ICU stay (absolute risk reduction [ARR], 0.086 [95% CI,
      0.017-0.150]; relative risk [RR], 0.57 [95% CI, 0.37-0.90]; P = .01). Occurrences
      were lower in the conservative oxygen therapy group for new shock episode (ARR,
      0.068 [95% CI, 0.020-0.120]; RR, 0.35 [95% CI, 0.16-0.75]; P = .006) or liver
      failure (ARR, 0.046 [95% CI, 0.008-0.088]; RR, 0.29 [95% CI, 0.10-0.82]; P = .02)
      and new bloodstream infection (ARR, 0.05 [95% CI, 0.00-0.09]; RR, 0.50 [95% CI,
      0.25-0.998; P = .049). Conclusions and Relevance: Among critically ill patients
      with an ICU length of stay of 72 hours or longer, a conservative protocol for
      oxygen therapy vs conventional therapy resulted in lower ICU mortality. These
      preliminary findings were based on unplanned early termination of the trial, and
      a larger multicenter trial is needed to evaluate the potential benefit of this
      approach. Trial Registration: clinicaltrials.gov Identifier: NCT01319643.

PMID- 27706467
TI  - Cardiovascular Biomarker Score and Clinical Outcomes in Patients With Atrial
      Fibrillation: A Subanalysis of the ENGAGE AF-TIMI 48 Randomized Clinical Trial.
AB  - Importance: Treatment decisions in atrial fibrillation (AF) are based on clinical
      assessment of risk. The CHA2DS2-VASc (cardiac failure or dysfunction,
      hypertension, age 65-74 [1 point] or >=75 years [2 points], diabetes mellitus,
      and stroke, transient ischemic attack or thromboembolism [2 points]-vascular
      disease, and sex category [female]) risk score is pragmatic and widely used but
      has only moderate discrimination. Objective: To develop and test a cardiovascular
      biomarker score for indication of risk in patients with AF. Design, Setting, and
      Participants: The ENGAGE AF-TIMI 48 trial was a randomized, double-blind, double
      dummy clinical trial comparing 2 once-daily edoxaban dose regimens with warfarin
      in 21 105 patients with AF at moderate to high risk of stroke. This prespecified
      subanalysis was performed in 4880 patients enrolled at randomization in the
      biomarker substudy. Cardiac troponin I, N-terminal pro-B-type natriuretic
      peptide, and d-dimer levels were measured at baseline. A multimarker risk score
      was developed to determine the probability of stroke, systemic embolic events, or
      death by assigning tiered points for higher concentrations of the biomarkers.
      Main Outcomes and Measures: Risk score and clinical outcomes based on cardiac
      troponin I, N-terminal pro-B-type natriuretic peptide, and d-dimer levels at
      baseline. Results: Of the 5002 patients enrolled in the biomarker substudy of the
      ENGAGE AF-TIMI 48 trial, 4880 patients (97.6%) had all 3 biomarkers available at
      randomization (1820 [37.3%] were women; median [interquartile range] age, 71 [64
      77] years). After adjustment for the CHA2DS2-VASc score, each biomarker was
      associated with a 2.8-fold to 4.2-fold gradient of risk comparing the highest vs
      lowest concentrations across groups of increasing concentrations (P < .001 for
      trend for each). The multimarker risk score identified a more than 15-fold
      gradient of risk after adjustment for CHA2DS2-VASc score. When added to the
      CHA2DS2-VASc score, the biomarker score significantly enhanced prognostic
      accuracy by improving the C statistic from 0.586 (95% CI, 0.565-0.607) to 0.708
      (95% CI, 0.688-0.728) (P < .001) and reclassification with a net reclassification
      improvement of 59.4% (P < .001). Conclusions and Relevance: A prototype
      multimarker risk score significantly enhanced risk assessment for stroke,
      systemic embolic events, or death compared with traditional clinical risk
      stratification. Incorporation of biomarkers into clinical decision making to
      define therapeutic management in AF warrants consideration. Trial Registration:
      clinicaltrials.gov Identifier: NCT00781391.

PMID- 27706468
TI  - Same-Day Discharge After Percutaneous Coronary Intervention: Additional Data on
      High-Risk Patients With Acute Coronary Syndrome.

PMID- 27706469
TI  - Oxygen in the ICU: Too Much of a Good Thing?

PMID- 27706470
TI  - Comparison of Approaches for Heart Failure Case Identification From Electronic
      Health Record Data.
AB  - Importance: Accurate, real-time case identification is needed to target
      interventions to improve quality and outcomes for hospitalized patients with
      heart failure. Problem lists may be useful for case identification but are often
      inaccurate or incomplete. Machine-learning approaches may improve accuracy of
      identification but can be limited by complexity of implementation. Objective: To
      develop algorithms that use readily available clinical data to identify patients
      with heart failure while in the hospital. Design, Setting, and Participants: We
      performed a retrospective study of hospitalizations at an academic medical
      center. Hospitalizations for patients 18 years or older who were admitted after
      January 1, 2013, and discharged before February 28, 2015, were included. From a
      random 75% sample of hospitalizations, we developed 5 algorithms for heart
      failure identification using electronic health record data: (1) heart failure on
      problem list; (2) presence of at least 1 of 3 characteristics: heart failure on
      problem list, inpatient loop diuretic, or brain natriuretic peptide level of 500
      pg/mL or higher; (3) logistic regression of 30 clinically relevant structured
      data elements; (4) machine-learning approach using unstructured notes; and (5)
      machine-learning approach using structured and unstructured data. Main Outcomes
      and Measures: Heart failure diagnosis based on discharge diagnosis and physician
      review of sampled medical records. Results: A total of 47 119 hospitalizations
      were included in this study (mean [SD] age, 60.9 [18.15] years; 23 952 female
      [50.8%], 5258 black/African American [11.2%], and 3667 Hispanic/Latino [7.8%]
      patients). Of these hospitalizations, 6549 (13.9%) had a discharge diagnosis of
      heart failure. Inclusion of heart failure on the problem list (algorithm 1) had a
      sensitivity of 0.40 and a positive predictive value (PPV) of 0.96 for heart
      failure identification. Algorithm 2 improved sensitivity to 0.77 at the expense
      of a PPV of 0.64. Algorithms 3, 4, and 5 had areas under the receiver operating
      characteristic curves of 0.953, 0.969, and 0.974, respectively. With a PPV of
      0.9, these algorithms had associated sensitivities of 0.68, 0.77, and 0.83,
      respectively. Conclusions and Relevance: The problem list is insufficient for
      real-time identification of hospitalized patients with heart failure. The high
      predictive accuracy of machine learning using free text demonstrates that support
      of such analytics in future electronic health record systems can improve cohort
      identification.

PMID- 27706471
TI  - Prenatal and Perinatal Risk Factors and the Promise of Birth Cohort Studies:
      Origins of Obsessive-Compulsive Disorder.

PMID- 27706472
TI  - Painful Ulcerative Lesions on Bilateral Lower Extremities.

PMID- 27706473
TI  - Variation in Medicare Expenditures for Treating Perioperative Complications: The
      Cost of Rescue.
AB  - Importance: Treating surgical complications presents a major challenge for
      hospitals striving to deliver high-quality care while reducing costs. Costs
      associated with rescuing patients from perioperative complications are poorly
      characterized. Objective: To evaluate differences across hospitals in the costs
      of care for patients surviving perioperative complications after major inpatient
      surgery. Design, Setting, and Participants: Retrospective cohort study using
      claims data from the Medicare Provider Analysis and Review files. We compared
      payments for patients who died vs patients who survived after perioperative
      complications occurred. Hospitals were stratified using average payments for
      patients who survived following complications, and payment components were
      analyzed across hospitals. Administrative claims database of surgical patients
      was analyzed at hospitals treating Medicare patients nationwide. This study
      included Medicare patients aged 65 to 100 years who underwent abdominal aortic
      aneurysm repair (n = 69 207), colectomy for cancer (n = 107 647), pulmonary
      resection (n = 91 758), and total hip replacement (n = 307 399) between 2009 and
      2012. Data analysis took place between November 2015 and March 2016. Exposures:
      Clinical outcome of surgery (eg, no complication, complication and death, or
      complication and survival) and the individual hospital where a patient received
      an operation. Main Outcomes and Measures: Risk-adjusted, price-standardized
      Medicare payments for an episode of surgery. Risk-adjusted perioperative outcomes
      were also assessed. Results: The mean age for Medicare beneficiaries in this
      study ranged from 74.1 years (pulmonary resection) to 78.2 years (colectomy). The
      proportion of male patients ranged from 37% (total hip replacement) to 77%
      (abdominal aortic aneurysm repair), and most patients were white. Among patients
      who experienced complications, those who were rescued had higher price
      standardized Medicare payments than did those who died for all 4 operations.
      Assessing variation across hospitals, payments for patients who were rescued at
      the highest cost-of-rescue hospitals were 2- to 3-fold higher than at the lowest
      cost-of-rescue hospitals for abdominal aortic aneurysm repair ($60 456 vs $23
      261; P < .001), colectomy ($56 787 vs $22 853; P < .001), pulmonary resection
      ($63 117 vs $21 325; P < .001), and total hip replacement ($41 354 vs $19 028; P
      < .001). Compared with lowest cost-of-rescue hospitals, highest cost-of-rescue
      hospitals had higher risk-adjusted rates of serious complications with similar
      rates of failure to rescue and overall 30-day mortality. Conclusions and
      Relevance: After 4 selected inpatient operations, substantial variation was
      observed across hospitals regarding Medicare episode payments for patients
      rescued from perioperative complications. Notably, higher Medicare payments were
      not associated with improved clinical performance. These findings highlight the
      potential for hospitals to target efficient treatment of perioperative
      complications in cost-reduction efforts.

PMID- 27706474
TI  - Omitted Reference.

PMID- 27706475
TI  - Association of Perinatal Risk Factors With Obsessive-Compulsive Disorder: A
      Population-Based Birth Cohort, Sibling Control Study.
AB  - Importance: Perinatal complications may increase the risk of obsessive-compulsive
      disorder (OCD). Previous reports were based on small, retrospective, specialist
      clinic-based studies that were unable to rigorously control for unmeasured
      environmental and genetic confounding. Objective: To prospectively investigate a
      wide range of potential perinatal risk factors for OCD, controlling for
      unmeasured factors shared between siblings in the analyses. Design, Setting, and
      Participants: This population-based birth cohort study included all 2 421 284
      children from singleton births in Sweden from January 1, 1973, to December 31,
      1996, who were followed up through December 31, 2013. From the 1 403 651 families
      in the cohort, differentially exposed siblings from the 743 885 families with
      siblings were evaluated; of these, 11 592 families included clusters of full
      siblings that were discordant for OCD. Analysis of the data was conducted from
      January, 26, 2015, to September, 5, 2016. Exposures: Perinatal data were
      collected from the Swedish Medical Birth Register and included maternal smoking
      during pregnancy, labor presentation, obstetric delivery, gestational age (for
      preterm birth), birth weight, birth weight in relation to gestational age, 5
      minute Apgar score, and head circumference. Main Outcomes and Measures:
      Previously validated OCD codes (International Statistical Classification of
      Diseases and Health Related Problems, Tenth Revision, code F42) in the Swedish
      National Patient Register. Results: Of 2 421 284 individuals included in the
      cohort, 17 305 persons were diagnosed with OCD. Of these, 7111 were men (41.1%).
      The mean (SD) age of individuals at first diagnosis of OCD was 23.4 (6.5) years.
      An increased risk for OCD remained after controlling for shared familial
      confounders and measured covariates (including sex, year of birth, maternal and
      paternal age at birth, and parity), for smoking 10 or more cigarettes per day
      during pregnancy (hazard ratio [HR], 1.27; 95% CI, 1.02-1.58), breech
      presentation (HR, 1.35; 95% CI, 1.06-1.71), delivery by cesarean section (HR,
      1.17; 95% CI, 1.01-1.34), preterm birth (HR, 1.24; 95% CI, 1.07-1.43), birth
      weight 1501 to 2500 g (HR, 1.30; 95% CI, 1.05-1.62) and 2501 to 3500 g (HR, 1.08;
      95% CI, 1.01-1.16), being large for gestational age (HR, 1.23; 95% CI, 1.05
      1.45), and Apgar distress scores at 5 minutes (HR, 1.50; 95% CI, 1.07-2.09).
      Gestational age and birth weight followed inverse dose-response associations,
      whereby an increasingly higher risk for OCD was noted in children with a shorter
      gestational age and lower birth weight. We also observed a dose-response
      association between the number of perinatal events and increased OCD risk, with
      HRs ranging from 1.11 (95% CI, 1.07-1.15) for 1 event to 1.51 (95% CI, 1.18-1.94)
      for 5 or more events. Conclusions and Relevance: A range of perinatal risk
      factors is associated with a higher risk for OCD independent of shared familial
      confounders, suggesting that perinatal risk factors may be in the causal pathway
      to OCD.

PMID- 27706476
TI  - Successful Treatment of Refractory Pityriasis Rubra Pilaris With Secukinumab.

PMID- 27706477
TI  - Black and Hispanic Caregivers' Behaviors, Motivations, and Barriers to Sun
      Protection in Children Aged 4 to 12 Years in Miami, Florida.

PMID- 27706478
TI  - Exploring the Industry-Dermatologist Financial Relationship: Insight From the
      Open Payment Data.
AB  - Importance: Significant ties exist between clinicians and industry. Little is
      known about the characteristics of industry payments to dermatologists.
      Objective: To analyze the nature and extent of industry payments to
      dermatologists. Design, Setting, and Participants: This was a retrospective
      review using the publicly available Centers for Medicare and Medicaid Services
      (CMS) Sunshine Act Open Payment database. Data were downloaded from the
      publically available CMS website under General Payment and Research Payment data
      sets. All payments to dermatologists from companies making products reimbursed by
      a government-run health program were reviewed. Main Outcomes and Measures: Mean,
      median, and range of payments made, including quantity and total sum of payments,
      per clinician. Total payments and number of transactions per category of payment,
      geographic region, and payment source were also assessed. Results: A total of
      8333 dermatologists received 208 613 payments totaling more than $34 million. The
      median total payment per dermatologist was $298 with an interquartile range of
      $99 to $844. The top 10% of dermatologists (n = 833) received more than $31.2
      million, 90% of the total payments. The top 1% each (n = 83) received at least
      $93 622 and accounted for 44% of total payments. While 83% of payment entries
      were for food and beverage, they accounted for only 13% of total amount of
      payments. Speaker fees (31.7%), consulting fees (21.6%), and research payments
      (16.5%) comprised 69.8% of total payment amount. The top 15 companies were all
      pharmaceutical manufacturers and paid dermatologists $28.7 million, representing
      81% of total disbursement. Conclusions and Relevance: Dermatologists received
      substantial payments from the pharmaceutical industry. The nature and amount of
      payments varied widely. The impact of the data on patient care, physicians
      practice patterns, and patient perception of physicians is unclear.

PMID- 27706480
TI  - Transparency Associated With Interactions Between Industry and Physicians:
      Deficits in Accuracy and Consistency of Public Data Releases.

PMID- 27706479
TI  - Evaluation of Patients With Hepatocellular Carcinomas That Do Not Produce alpha
      Fetoprotein.
AB  - Importance: Serum alpha-fetoprotein (AFP) is a biomarker for hepatocellular
      carcinomas (HCCs) associated with a more aggressive tumor phenotype and inferior
      outcomes after a liver transplant (LT). Data on the outcomes for patients with
      HCCs that do not produce AFP are limited. Objective: To compare characteristics
      and outcomes among LT recipients with radiographically apparent HCC lesions with
      AFP-producing tumors or with tumors that do not produce AFP (hereafter referred
      to as non-AFP-producing tumors), and to identify factors influencing recurrence
      in LT recipients with non-AFP-producing tumors. Design, Setting, and
      Participants: Retrospective analysis at a university transplant center of 665
      adults with HCC who underwent an LT during the period from 1989 to 2013. Of the
      665 LT recipients, 457 (68.7%) had AFP-producing tumors, and 208 (31.3%) had non
      AFP-producing tumors (the maximum AFP level before an LT was <=10 ng/mL). Dates
      of study analysis were from August 2015 to June 2016. Intervention: Liver
      transplant. Main Outcomes and Measures: Recurrence-free survival and recurrence
      rates. Results: Patients with non-AFP-producing tumors had radiographic tumor
      characteristics similar to those of patients with AFP-producing tumors, but,
      pathologically, they had fewer lesions (25% vs 35% with >2 lesions; P = .03),
      smaller cumulative tumor diameters (4.2 vs 5.0 cm; P = .02), fewer microvascular
      (17% vs 22%) and macrovascular (2% vs 9%) invasions (P < .001), and fewer poorly
      differentiated tumors (15% vs 28%; P < .001). Patients with non-AFP-producing
      tumors also had significantly superior recurrence-free survival at 1, 3, and 5
      years (88%, 74%, and 67% vs 76%, 59%, and 51%, respectively; P = .002) and lower
      5-year recurrence rates (8.8% vs 22%; P < .001) than patients with AFP-producing
      tumors. When stratified by radiologic Milan criteria, 5-year survival was better,
      and recurrence lowest, among patients with non-AFP-producing tumors within the
      Milan criteria (71% survival and 6% recurrence), and survival was worse, and
      recurrence highest, for patients with AFP-producing tumors outside the Milan
      criteria (40% survival and 42% recurrence; P < .001). Significant predictors of
      recurrence among patients with non-AFP-producing tumors include radiologic (>2
      tumors [HR, 4.98; 95% CI, 1.72-14.4; P = .003]; cumulative diameter [1.70 per log
      SD; 1.12-2.59; P < .001]; outside the Milan criteria [10.0; 3.7-33.3; P < .001)
      and pathologic factors (>2 tumors [4.39; 1.32-14.6; P = .02]; cumulative diameter
      [2.32 per log SD; 1.43-3.77; P = .001]; microvascular [3.07; 1.02-9.24; P = .05]
      and macrovascular invasion [8.75; 2.15-35.6; P = .002]). Conclusions and
      Relevance: Nearly one-third of patients with radiographically apparent HCC have
      non-AFP-producing tumors that have more favorable pathologic characteristics,
      lower posttransplant recurrence, and superior survival compared with patients
      with AFP-producing tumors. Posttransplant HCC recurrence for patients with non
      AFP-producing tumors is predicted by important radiologic and pathologic factors,
      and is negligible for patients within the Milan criteria. Stratifying patients by
      AFP status in addition to radiological criteria may improve the selection process
      for and the prioritization of transplant candidates.

PMID- 27706481
TI  - A Massive Retroperitoneal Mass With Leukocytosis.

PMID- 27706482
TI  - Global Outreach Using a Systematic, Competency-Based Training Paradigm for
      Inguinal Hernioplasty.
AB  - Importance: Sustainable, capacity-building educational collaborations are
      essential to address the global burden of surgical disease. Objective: To assess
      an international, competency-based training paradigm for hernia surgery in
      underserved countries. Design, Setting, and Participants: In this prospective,
      observational study performed from November 1, 2013, through October 31, 2015, at
      16 hospitals in Brazil, Ecuador, Haiti, Paraguay, and the Dominican Republic,
      surgeons completed initial training programs in hernia repair, underwent interval
      proficiency assessments, and were appointed regional trainers. Competency-based
      evaluations of technical proficiency were performed using the Operative
      Performance Rating Scale (OPRS). Maintenance of proficiency was evaluated by
      video assessments 6 months after training. Certified trainees received incentives
      to document independent surgical outcomes after training. Main Outcomes and
      Measures: An OPRS score of 3.0 (scale of 1 [poor] to 5 [excellent]) indicated
      proficiency. Secondary outcomes included initial vs final scores by country,
      scores among surgeons trained by the regional trainers (second-order trainees),
      interval scores 6 months after training, and postoperative complications.
      Results: A total of 20 surgeon trainers, 81 local surgeons, and 364 patients (343
      adult, 21 pediatric) participated in the study (mean [SD] age, 47.5 [16.3] years;
      age range, 16-83 years). All 81 surgeons successfully completed the program, and
      all 364 patients received successful operations. Mean (SD) OPRS scores improved
      from 4.06 (0.87) before the initial training program to 4.52 (0.57) after
      training (P < .001). No significant variation was found by country in final
      scores. On trainee certification, 20 became regional trainers. The mean (SD) OPRS
      score among 53 second-order trainees was 4.34 (0.68). After 6-month intervals,
      the mean (SD) OPRS score among participating surgeons was 4.34 (0.55). The
      overall operative complication rate during training series was 1.1%. Conclusions
      and Relevance: Competency-based training helps address the global burden of
      surgical disease. The OPRS establishes an international standard of technical
      assessment. Additional studies of long-term surgeon trainer proficiency,
      community-specific quality initiatives, and expansion to other operations are
      warranted.

PMID- 27706483
TI  - Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in
      Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ
      Failure: The EMPIRICUS Randomized Clinical Trial.
AB  - Importance: Although frequently used in treating intensive care unit (ICU)
      patients with sepsis, empirical antifungal therapy, initiated for suspected
      fungal infection, has not been shown to improve outcome. Objective: To determine
      whether empirical micafungin reduces invasive fungal infection (IFI)-free
      survival at day 28. Design, Setting, and Participants: Multicenter double-blind
      placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill
      patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ
      failure, exposed to broad-spectrum antibacterial agents, and enrolled between
      July 2012 and February 2015 in 19 French ICUs. Interventions: Empirical treatment
      with micafungin (100 mg, once daily, for 14 days) (n = 131) vs placebo (n = 129).
      Main Outcomes and Measures: The primary end point was survival without proven IFI
      28 days after randomization. Key secondary end points included new proven fungal
      infections, survival at day 28 and day 90, organ failure, serum (1-3)-beta-D
      glucan level evolution, and incidence of ventilator-associated bacterial
      pneumonia. Results: Among 260 patients (mean age 63 years; 91 [35%] women), 251
      (128, micafungin group; 123, placebo group) were included in the modified intent
      to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment
      (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of
      (1-3)-beta-D-glucan. On day 28, there were 82 (68%) patients in the micafungin
      group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard
      ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a
      (1-3)-beta-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI,
      0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (>8) was
      not significantly different when compared between the micafungin vs placebo
      groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the
      rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin
      group vs placebo (15/123 patients [12%]) (P = .008). Conclusions and Relevance:
      Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida
      species colonization at multiple sites, and multiple organ failure, empirical
      treatment with micafungin, compared with placebo, did not increase fungal
      infection-free survival at day 28. Trial Registration: clinicaltrials.gov
      Idenitfier: NCT01773876.

PMID- 27706484
TI  - Enhancing Local Resources in Low- and Middle-Income Countries Through Education.

PMID- 27706485
TI  - Better Suicide Screening and Prevention Are Possible.

PMID- 27706486
TI  - Are There Still Too Few Suicides to Generate Public Outrage?

PMID- 27706489
TI  - Computer-Assisted Process Modeling to Enhance Intraoperative Safety in Cardiac
      Surgery.

PMID- 27706490
TI  - Association of Uneven MitraClip Application and Leaflet Stress in a Finite
      Element Model.

PMID- 27706491
TI  - Promise and Pitfalls of Using alpha-Fetoprotein in Liver Transplantation
      Allocation for Hepatocellular Carcinoma.

PMID- 27706492
TI  - Work ability index and perceived work ability as predictors of disability
      pension: a prospective study among Finnish municipal employees.
AB  - OBJECTIVES: We analyzed the work ability index (WAI) and its first item (work
      ability score, WAS) - and subsequent four-year changes thereof - as predictors of
      disability pension (DP). METHODS: We linked survey responses of 5251 Finnish
      municipal employees, aged 44-58 years, to pension and death register data until
      2009. Job content (physical, mental, or mixed) was based on observation. Baseline
      (1981) WAI was divided into poor (<27), moderate (28-36), and good/excellent
      (>37) and WAS into poor (0-5), moderate (6-7), and good/excellent (8-10). Four
      year changes in these scores were classified as strong decline (<lowest 15th
      percentile), slight decline, and no change/improved. Cox regression and receiver
      operating characteristic (ROC) analysis were used. RESULTS: During follow-up,
      2057 subjects were granted DP. Compared to those with good/excellent WAI, the
      hazard ratio (HR) for DP related to moderate and poor WAI, respectively, was 2.0
      (95% CI 1.8-2.2) and 5.0 (95% CI 4.4-5.6), adjusted for sociodemographic
      variables and job content. For WAS, the HR were 1.8 (95% CI 1.6-2.0) and 3.4 (95%
      3.0-3.8). Four-year decline in WAI/WAS further increased the risk. During the
      first four years of follow-up, the area under the curve (AUC) for WAI at cut-off
      point 27 was 0.66 (sensitivity 49.2% and specificity 82.9%) and 0.64 for cut-off
      point 36 (sensitivity 84.2% and specificity 44.3%). For WAS at cut-off point 5,
      the figures were AUC 0.63 (sensitivity 41.9% and specificity 85.0%) and AUC 0.65
      for cut-off point 7 (sensitivity 78.2% and specificity 52.7%). CONCLUSION: The
      single-item WAS can be considered a reasonable alternative to the seven-item WAI
      in describing the risk of DP and as a prognostic tool.

PMID- 27706493
TI  - Evaluating Sustainable Development Goal Targets: A Physician's Perspective.

PMID- 27706494
TI  - Healthcare Industry Injuries by Patient Contact Status in Kentucky, 2012-2014.
AB  - OBJECTIVES: The healthcare industry continues to have a high number of reported
      injuries. The purpose of this study was to characterize healthcare industry
      injuries by patient contact status, identify the occupations associated with
      healthcare injuries by patient contact status, and determine healthcare injury
      rates by occupation to gain a better understanding of healthcare industry
      compensated injuries and better target safety practices and programs in the
      healthcare industry. METHODS: Kentucky healthcare industry workers' compensation
      first reports of injuries from calendar years 2012-2014 were categorized into
      injuries involved in direct patient contact versus injuries without direct
      patient contact using narrative text analysis. Injury numbers and rates were
      calculated for a number of data variables. RESULTS: Healthcare injuries without
      direct patient contact (55% of all first reports of injuries) occurred more
      frequently among older workers (45 years old and older [51%]), in "other"
      occupations such as housekeeping and maintenance (28%), and as a result of
      falls/slips/trips (39%) and sprains/tears (38%). In contrast, a higher percentage
      of healthcare injuries involving direct patient contact occurred among workers
      younger than 35 years (48%), in healthcare support occupations (50%), and
      resulting from sprains/tears (66%) and lifting/handling (52%), compared with
      those without direct patient contact. CONCLUSIONS: Findings from this study can
      better target the need for new and/or additional specific workplace safety
      training, especially in the healthcare support and nursing occupations with and
      without patient contact.

PMID- 27706495
TI  - Relations Between Residential Proximity to EPA-Designated Toxic Release Sites and
      Diffuse Large B-Cell Lymphoma Incidence.
AB  - OBJECTIVES: Examining the spatial patterns of diffuse large B-cell lymphoma
      (DLBCL) incidence and residential proximity to toxic release locations may
      provide insight regarding environmental and sociodemographic risk factors.
      METHODS: We linked and geocoded cancer incidence data for the period 1999-2008
      from the Georgia Comprehensive Cancer Registry with population data from the US
      Census and the Environmental Protection Agency's Toxics Release Inventory. We
      conducted cluster analyses and constructed Poisson regression models to assess
      DLBCL incidence as a function of mean distance to the toxic release sites.
      RESULTS: In total, 3851 incident DLBCL cases occurred among adults residing in
      Georgia between 1999 and 2008. Significant focal clustering was observed around
      57% of ethylene oxide sites, 5% of benzene sites, 9% of tetrachloroethylene
      sites, 7% of styrene sites, 10% of formaldehyde sites, 5% of trichloroethylene
      sites, and 10% of all release sites. Mean distance to sites was significantly
      associated with DLBCL risk for all chemicals. CONCLUSIONS: Proximity to Toxics
      Release Inventory sites can be linked to increased DLBCL risk as assessed through
      focal clustering and Poisson regression, and confirmatory studies using
      geospatial mapping can aid in further specifying risk factors for DLBCL.

PMID- 27706496
TI  - Body Mass Index and Physical Inactivity: 2013 BRFSS.
AB  - OBJECTIVES: Examine the odds of adults reporting physical inactivity (PI) across
      six body mass index (BMI) categories. METHODS: We used data from the 2013
      Behavioral Risk Factor Surveillance System. Six BMI categories were used.
      RESULTS: The odds of reporting PI in underweight men and men in the class I, II,
      and III obesity categories were 1.65 (95% confidence interval [CI] 1.35-2.02),
      1.30 (95% CI 1.21-1.39), 1.73 (95% CI 1.58-1.90), and 2.44 (95% CI 2.17-2.75),
      respectively, compared with men of desirable weight (odds ratio [OR] 1.00, 18.5
      24.9 kg/m2; referent, OR 1.00). The odds of reporting PI in underweight men were
      similar to class II and class III obese men. The odds of reporting PI in
      underweight women, overweight women, and women in the class I, II, and III
      obesity categories were 1.57 (95% CI 1.36-1.81), 1.20 (95% CI 1.14-1.27), 1.65
      (95% CI 1.56-1.75), 2.23 (95% CI 2.07-2.40), and 2.89 (95% CI 2.66-3.15),
      respectively, compared with women of desirable weight (>=18.5-24.9 kg/m2;
      referent, OR 1.00). The odds of reporting PI were similar in underweight and
      class I obese women. Women were found to have greater odds than men of reporting
      PI in four of the five nondesirable BMI categories (P < 0.05). CONCLUSIONS: The
      within- and between-sex differences in the odds of reporting PI vary
      significantly by BMI category. Future research needs to include the underweight
      BMI category when investigating PI and sedentary time because of the potential
      clinical relevance.

PMID- 27706497
TI  - On "I'm Dying, but I'm Not Dead Yet: Patient Decisions About Dying and Death".

PMID- 27706498
TI  - Editor's Response.

PMID- 27706499
TI  - Hormonal Contraceptives for Endometrial Cancer Prevention in Obese and High-Risk
      Women in Virginia.
AB  - OBJECTIVES: Endometrial cancer remains the fourth most common malignancy among US
      women, and hormonal contraceptives drastically reduce this risk. The study
      objectives were to assess the prescribing patterns, counseling practices, and
      knowledge of family physicians and obstetrician/gynecologists (OB/GYNs) regarding
      hormonal contraceptives, obesity, and cancer prevention. METHODS: A 25-question
      survey was mailed to 4600 OB/GYNs and family practitioners licensed in Virginia
      to assess self-reported hormonal contraceptive prescription practices, patient
      evaluation and counseling, and gynecologic oncology knowledge. chi2 and t tests
      were used to assess for differences across groups. P < 0.05 was deemed
      significant. RESULTS: In total, 392 (9%) surveys were returned, with 256 (6%)
      being complete for analysis. The mean physician age was 53.6 years, 50.2% were
      men, and 92.6% of physicians prescribed hormonal contraception. Most physicians
      recognized decreased endometrial cancer risk associated with oral contraceptive
      pills (73.0%) and increased risk with obesity (95.3%), but only 36.7%
      consistently counseled patients on obesity-associated cancer risk. Compared with
      family physicians, OB/GYNs were more likely to cite endometrial cancer prevention
      as an indication for hormonal contraceptives (53.3% vs 10.9%, P < 0.0001); more
      often counseled patients on obesity-related cancer risk (P = 0.003); and were
      more likely to correctly identify Lynch syndrome (69.4% vs 22.5%, P < 0.0001),
      diabetes mellitus (85.2% vs 38.8%, P < 0.0001), and hypertension (41.7% vs 10.1%,
      P < 0.0001) as risk factors for endometrial cancer. Endometrial or ovarian cancer
      prevention factored into <2% of total hormonal contraception prescriptions;
      however, OB/GYN physicians were more likely to prescribe for those indications
      than family physicians (P = 0.005 and P < 0.001, respectively). CONCLUSIONS:
      Family physicians and OB/GYNs could improve their knowledge of endometrial cancer
      risk factors and the use of hormonal contraception for chemoprevention. This
      represents a significant opportunity for both specialties to optimize primary
      endometrial cancer prevention in their increasingly obese and at-risk female
      patients.

PMID- 27706500
TI  - Pharmacogenomics Can Enhance Prescribing of Psychiatric Medications.
AB  - Many psychiatric patients experience pharmaceutical intolerances, and some of
      them do not derive optimal efficacy from their pharmacotherapies. Clinical
      problems such as these may result in prolonged dysfunction, adverse consequences,
      and repeated changes in medication treatment regimens. Pharmacogenomics is a
      laboratory method that aids individualized medication selection by predicting
      drug efficacy and adverse effect profiles. It is a technique that involves the
      testing of patients' genetic makeup to improve medicinal response and tolerance.
      Pharmacogenomics aims to clarify pharmacokinetics and pharmacodynamics in
      addition to focusing on hepatic cytochrome enzyme metabolism. Ultimately, it
      facilitates optimal selection and adjustment of medications to enhance clinical
      outcomes. Pharmacogenomics is most useful in cases in which routinely prescribed
      pharmacotherapies are either suboptimally effective or have unacceptable adverse
      effects. Once there has been a failure of a therapeutic drug treatment, rather
      than "blindly" selecting an alternative medicine, pharmacogenomic test results
      can provide guidance for the selection of the most appropriate drug and its dose.
      The intent is to yield a greater likelihood of patient success in following a
      therapeutic intervention.

PMID- 27706502
TI  - Diabetes Mellitus and the Skin: Recognition and Management of Cutaneous
      Manifestations.
AB  - Diabetes mellitus (DM) is a heterogeneous condition characterized by
      hyperglycemia as a consequence of defects in insulin secretion and variable
      degrees of insulin resistance. DM is the most common endocrine disorder in the
      United States, affecting 9.3% of the population (29.1 million people) in 2014.
      Skin disorders are present in 79.2% of patients with DM, and cutaneous disease
      may appear as the first sign of DM or develop at any time in the course of the
      disease. Given the increasing incidence and prevalence of DM in the United
      States, primary care physicians should be aware of the associated cutaneous
      manifestations. This clinical review provides a brief guide to primary care
      physicians for recognizing and managing skin conditions that they may encounter
      when caring for patients with DM.

PMID- 27706501
TI  - Frequency of Adverse Events Before, During, and After Hospital Admission.
AB  - OBJECTIVES: Adverse events (AEs) are unintended physical injuries resulting from
      or contributed to by medical or surgical care. We determined the frequency and
      type of AEs before, during, and after hospital admission. METHODS: We conducted a
      cohort study of 296 adult hospital patients. We used the standardized Institute
      for Healthcare Improvement Global Trigger Tool for Measuring Adverse Events to
      review the medical records of the hospital patients for occurrence, timing
      relative to hospital admission, severity, and preventability of AEs. We also
      identified the primary physiologic system affected by the AE. RESULTS: Among 296
      patients, we identified 338 AEs. AEs occurred with similar frequency before (n =
      148; 43.8%) and during hospital admission (n = 162; 47.9%). Fewer AEs occurred
      after discharge (n = 28; 8.3%). Half of all AEs (n = 169; 50.0%) were severe,
      whereas 47.9% (n = 162) were preventable. CONCLUSIONS: AEs occur with similar
      frequency before and during hospitalization and may contribute more to hospital
      admissions than previously recognized. These findings suggest that efforts to
      improve patient safety should include outpatient settings in addition to the more
      commonly targeted acute care settings.

PMID- 27706503
TI  - Commentary on "Diabetes Mellitus and the Skin: Recognition and Management of
      Cutaneous Manifestations".

PMID- 27706504
TI  - Should Antibiotic Allergy Alerts Be Alarming?
AB  - Allergies to various antibiotics are reported by a substantial proportion of
      patients. As a result, clinical decision support programming generates frequent
      warnings when prescribing within electronic medical records. For a variety of
      reasons, the majority of these warnings may be inappropriate. Our improved
      understanding of the underlying physiology of allergic processes reveals that the
      majority of cross-reacting antibiotic allergies are implausible. Appropriate
      history taking and workup can invalidate many more warnings. Electronic medical
      records ideally should permit documentation that would facilitate more accurate
      entry and eliminate similar future warnings.

PMID- 27706505
TI  - Commentary on "Should Antibiotic Allergy Alerts Be Alarming?"

PMID- 27706506
TI  - Hemophagocytic Lymphohistiocytosis and Bone Marrow Hemophagocytosis: A 5-Year
      Institutional Experience at a Tertiary Care Hospital.
AB  - OBJECTIVE: The purpose of this study was to correlate the significance of bone
      marrow hemophagocytosis and analyze outcome data in patients with suspected
      hemophagocytic lymphohistiocytosis (HLH) at a tertiary care hospital during the
      course of 5 years. METHODS: The pathology database of State University of New
      York Upstate Medical University, Syracuse, was searched for the terms
      "hemophagocytosis," "hemophagocytic syndrome," and "hemophagocytic
      lymphohistiocytosis" encompassing the period January 2009-December 2014. Bone
      marrow aspirate and biopsy specimens, along with ancillary laboratory studies,
      clinical course, and outcome data, were reviewed for each case. RESULTS: Of the
      23 patients included in our study, HLH was diagnosed in 14 (60.8%). Bone marrow
      hemophagocytosis (HPC) was seen in a higher proportion of patients (78.5%) who
      were diagnosed as having HLH; however, 55.5% of the patients who were not
      diagnosed as having HLH also showed evidence of bone marrow HPC. Patients with
      malignancy-associated HLH had a markedly worse outcome compared with patients
      with nonmalignancy-associated HLH. CONCLUSIONS: Although bone marrow HPC is
      fairly sensitive, it is not specific to establish a diagnosis of HLH. A high
      index of clinical suspicion together with early diagnosis and treatment is
      imperative to improve outcomes in patients suspected of having HLH.

PMID- 27706508
TI  - Commentary on "Intravenous Thrombolysis Attenuates Neurologic Deterioration After
      Ischemic Stroke".

PMID- 27706507
TI  - Intravenous Thrombolysis Attenuates Neurologic Deterioration After Ischemic
      Stroke.
AB  - INTRODUCTION: Although intravenous tissue plasminogen activator (IV tPA) is
      associated with neurologic deterioration (ND) caused by hemorrhage, whether it
      attenuates deterioration as a result of other etiologies including progressive
      stroke remains unexplored. The objective of this study was to determine whether
      IV tPA is associated with a reduced risk of ND caused by progressive stroke.
      METHODS: A retrospective investigation of consecutively admitted patients with
      acute ischemic stroke (July 2008-June 2014) within 4.5 hours of symptom onset was
      conducted at a tertiary care center. Patients treated with IV tPA were compared
      with those who were not. The primary outcome was ND resulting from progressive
      infarction (a two-point increase in the National Institutes of Health Stroke
      Scale score during a 24-hour period). RESULTS: A total of 699 registry patients
      (median age 65 years, interquartile range 55-76, 48.4% women, 70.4% nonwhite)
      were included in the study, and 58.1% received IV tPA. In crude regression, IV
      tPA did not reduce the odds of ND caused by progressive infarction; however, IV
      tPA-treated patients were at a 55% lower odds of ND from any cause (odds ratio
      0.45, 95% confidence interval 0.32-0.61, P < 0.001). After adjusting for
      covariates, IV tPA use remained strongly associated with a 39% lower odds of ND
      from any cause (odds ratio 0.61, 95% confidence interval 0.48-0.79, P < 0.001).
      CONCLUSIONS: Although IV tPA did not correlate with a reduced odds of progressive
      infarction, it was significantly associated with a lower odds of ND by any
      mechanism.

PMID- 27706509
TI  - Atrioventricular Accessory Pathways: Mechanisms, Electrocardiograms, and
      Associated Arrhythmias.
AB  - An atrioventricular accessory pathway (AP) may be manifest or concealed. When
      manifest, it leads to preexcitation on the baseline electrocardiogram, which is
      called the Wolff-Parkinson-White pattern. The degree of preexcitation varies
      according to the relative conduction speed of the atrioventricular node versus
      the AP, the AP location, and the AP refractory period. This explains that even a
      manifest AP may lead to only intermittent preexcitation. The AP conducts faster
      than the atrioventricular node but has a longer refractory period, which allows
      the initiation of a reentrant arrhythmia called atrioventricular reciprocating
      tachycardia. In addition to re-entry, a manifest AP may allow the fast antegrade
      conduction of an atrial tachyarrhythmia, leading to a small risk of sudden death;
      the latter depends on the AP refractory period (ie, the number of atrial waves it
      can conduct back to back) rather than the AP conduction speed. This can be
      assessed invasively and noninvasively and allows risk stratification of
      asymptomatic individuals.

PMID- 27706510
TI  - Unattended Sleep Studies in a VA Population: Initial Evaluation by Chart Review
      Versus Clinic Visit by a Midlevel Provider.
AB  - OBJECTIVES: Obstructive sleep apnea (OSA) is a prevalent disorder that is
      associated with multiple medical consequences. Although in-laboratory
      polysomnography is the gold standard for the diagnosis of OSA, portable monitors
      have been developed and studied to help increase efficiency and ease of
      diagnosis. We aimed to assess the adequacy of a midlevel provider specializing in
      sleep medicine to risk-stratify patients for OSA based on a chart review versus a
      comprehensive clinic evaluation before scheduling an unattended sleep study.
      METHODS: This study was an observational, nonrandomized, retrospective data
      collection by chart review of patients accrued prospectively who underwent an
      unattended sleep study at the Sleep Health Center at the Memphis Veterans Affairs
      Medical Center during the first 13 months of the program (May 1, 2011-May 31,
      2012). A total of 205 patients were included in the data analysis. RESULTS:
      Analysis showed no statistically significant differences between chart review and
      clinic visit groups (P = 0.54) in terms of OSA diagnosis. Although not
      statistically significant, the analysis shows a trend toward higher mean age
      (50.3 vs 47.4 years; P = 0.10) and lower mean body mass index (34.4 vs 36.0; P =
      0.08) in individuals who were evaluated during a comprehensive clinic visit. A
      statistically significant difference is seen in terms of the pretest clinical
      probability of OSA being moderate or high in 62.2% of patients in the clinic
      visit group and 95.7% in the chart review group, with a chi2P <= 0.0001.
      CONCLUSIONS: In the Veterans Health Administration's system, the assessment of
      pretest probability may be determined by a midlevel provider using chart review
      with equal efficacy to a comprehensive face-to-face evaluation in terms of OSA
      diagnosis via unattended sleep studies.

PMID- 27706511
TI  - ?

PMID- 27706512
TI  - ?

PMID- 27706513
TI  - ?

PMID- 27706515
TI  - ?

PMID- 27706514
TI  - ?

PMID- 27706516
TI  - ?

PMID- 27706517
TI  - ?

PMID- 27706518
TI  - ?

PMID- 27706519
TI  - ?

PMID- 27706520
TI  - ?

PMID- 27706521
TI  - ?

PMID- 27706522
TI  - ?

PMID- 27706523
TI  - Rapid Response Team Activations in Pediatric Surgical Patients.
AB  - Introduction The rapid response team (RRT) is a multidisciplinary team who
      evaluates hospitalized patients for concerns of nonemergent clinical
      deterioration. RRT evaluations are mandatory for children whose Pediatric Early
      Warning System (PEWS) score (assessment of child's behavior, cardiovascular and
      respiratory status) is >=4. We aimed to determine if there were differences in
      characteristics of RRT calls between children who were admitted primarily to
      either medical or surgical services. We hypothesized that RRT activations would
      be called for less severely ill children with lower PEWS score on surgical
      services compared with children admitted to a medical service. Materials and
      Methods We performed a retrospective review of all children with RRT activations
      between January 2008 and April 2015 at a tertiary care pediatric hospital. We
      evaluated the characteristics of RRT calls and made comparisons between RRT calls
      made for children admitted primarily to medical or surgical services. Results A
      total of 2,991 RRT activations were called, and 324 (11%) involved surgical
      patients. Surgical patients were older than medical patients (median: 7 vs. 4
      years; p < 0.001). RRT evaluations were called for lower PEWS score in surgical
      patients compared with medical (median: 3 vs. 4, p < 0.001). Surgical patients
      were more likely to remain on the inpatient ward following the RRT (51 vs. 39%, p
      < 0.001) and were less likely to require an advanced airway than medical patients
      (0.9 vs. 2.1%; p = 0.412). RRT evaluations did not differ between day and night
      shifts (52% day vs. 48% night; p = 0.17). All surgical patients and all but one
      medical patient survived the event; surgical patients were more likely to survive
      to hospital discharge (97 vs. 91%, p < 0.001) Conclusions RRT activations are
      rare events among pediatric surgical patients. When compared with medical
      patients, RRT evaluation is requested for surgical patients with a lower PEWS
      score and these children are less likely to require transfer to a higher level of
      care, suggesting that pediatric surgery team, families, and nursing staff may not
      be as comfortable with clinical deterioration.

PMID- 27706524
TI  - Are Scores Reliable in Predicting the Need for Surgery and Mortality in
      Necrotizing Enterocolitis?
AB  - Background Management of children with necrotizing enterocolitis (NEC) remains
      challenging. Various scores try to facilitate therapeutic decision-making. We aim
      to assess the agreement of three scores intending to predict the need for surgery
      and/or mortality in our patient cohort, and analyze agreement between the
      different scores. Methods This study is a retrospective analysis of patients with
      NEC Bell's stage II and III, managed in a single institution (1991-2011). Three
      existing scores (Metabolic Derangement Acuity score, NEC score, Detroit score)
      were calculated individually for each patient. The agreement between predicted
      outcome by scores and real outcome was evaluated with kappa statistic. Results Of
      57 children, 46% presented with NEC stage II, 54% with stage III, 46% were
      treated with surgery, 54% conservatively, and survival was 58%. The kappa indexes
      for "need for surgery" were 0.41, 0.13, and 0.12 and kappa indexes for
      "mortality" were 0.27, 0.04, and 0.1 for the Metabolic Derangement Acuity score,
      the NEC score, and the Detroit score, respectively. Conclusion In our cohort, the
      agreement between the predicted outcomes by scores and the real need for surgery
      and/or mortality was poor. There was a lack of clinical usefulness of the tested
      scores. We must continue to better identify parameters to help guide the
      management of these patients.

PMID- 27706525
TI  - Endoscopic treatment of post-laparoscopic sleeve gastrectomy leaks using a
      specifically designed metal stent.
AB  - Background and study aim Leakage of the surgical suture is the main complication
      of laparoscopic sleeve gastrectomy (LSG) and is amenable to endoscopic therapy.
      The aim of this study was to evaluate the efficacy of a specifically designed
      self-expandable metal stent (SEMS) to seal the leakage. Patients and methods Over
      a 2-year period, patients referred for the treatment of post-LSG fistulas
      underwent placement of a fully covered esophagogastric SEMS with a specific
      design. Results A total of 10 patients were treated after a mean time of 50.9
      days from the diagnosis of post-LSG leakage. A total of 11 SEMSs were placed.
      After stent removal, the leakage was seen to have healed in eight patients. Two
      patients who were treated with an SEMS with different mesh design, experienced
      stent migration, which required alternative endoscopic treatment such as the
      insertion of double-pigtail stents. After a mean follow-up period of 13.4 months,
      all patients were asymptomatic. Conclusions: Placement of a specifically designed
      SEMS for the treatment of post-LSG fistulas seems a promising first-line therapy
      according to this small series.

PMID- 27706526
TI  - Randomized comparative evaluation of endoscopic submucosal dissection self
      learning software in France and Japan.
AB  - Background and study aim: Endoscopic submucosal dissection (ESD) is currently the
      reference method to achieve an en bloc resection for large lesions; however, the
      technique is difficult and risky, with a long learning curve. In order to reduce
      the morbidity, training courses that use animal models are recommended. Recently,
      self-learning software has been developed to assist students in their training.
      The aim of this study was to evaluate the impact of this tool on the ESD learning
      curve. Methods: A prospective, randomized, comparative study enrolled 39 students
      who were experienced in interventional endoscopy. Each student was randomized to
      one of two groups and performed 30 ESDs of 30 mm standardized lesions in a bovine
      colon model. The software group used the self-learning software whereas the
      control group only observed an ESD procedure video. The primary outcome was the
      rate of successful ESD procedures, defined as complete en bloc resection without
      any perforation and performed in less than 75 minutes. Results: A total of 39
      students performed 1170 ESDs. Success was achieved in 404 (70.9 %) in the
      software group and 367 (61.2 %) in the control group (P = 0.03). Among the
      successful procedures, there were no significant differences between the software
      and control groups in terms of perforation rate (22 [4.0 %] vs. 29 [5.1 %],
      respectively; P = 0.27) and mean (SD) procedure duration (34.1 [13.4] vs. 32.3
      [14.0] minutes, respectively; P = 0.52). For the 30th procedure, the rate of
      complete resection was superior in the software group (84.2 %) compared with the
      control group (50.0 %; P = 0.01). Conclusion: ESD self-learning software was
      effective in improving the quality of resection compared with a standard teaching
      method using procedure videos. This result suggests the benefit of incorporating
      such software into teaching programs.

PMID- 27706527
TI  - Two-Stage Indicators to Assess Learning Curves for Minimally Invasive Ivor Lewis
      Esophagectomy.
AB  - BACKGROUND: Minimally invasive esophagectomy (MIE) Ivor Lewis has been
      increasingly performed over the last two decades. To guide the implementation of
      this technically demanding procedure, a comprehensive assessment of MIE-Ivor
      Lewis learning curves should include both the general competence to accomplish
      the procedure and the ability to generate oncological benefits. These objectives
      are believed to be associated with different phases of the learning curve.
      METHODS: A retrospective review of the first 109 patients who underwent MIE-Ivor
      Lewis by a single qualified surgeon was conducted. Relevant variables were
      collected and assessed by regression analysis to identify suitable indicators for
      patient stratification and learning curve assessment. Thereafter, the
      differential analysis was performed among groups to validate the learning curve
      model. RESULTS: Two variables, intrathoracic gastroesophageal anastomosis time
      and bilateral recurrent laryngeal nerve (RLN) lymphadenectomy number, which
      plateaued, respectively, after the 26th and 88th cases, were selected as
      meaningful indicators to identify different competence levels. Therefore, 109
      patients were chronologically subcategorized into three groups (the first 26 MIEs
      as the early group, the next 62 cases as the middle group, and 21 most recent
      cases as the late group). Perioperative data were compared between groups with
      positive results to indicate a three-phase model for a learning curve for MIE
      Ivor Lewis. CONCLUSIONS: An MIE-Ivor Lewis learning curve should include three
      discrete phases that indicate, successively, unskilled operation (general
      competence to accomplish, less proficiency), surgical proficiency, and
      oncological efficacy. Intrathoracic anastomosis time and bilateral RLN
      lymphadenectomy were identified as suitable indicators delineate the different
      stages of an MIE-Ivor Lewis learning curve.

PMID- 27706528
TI  - ["Breast Reconstruction Fellowship" at the University of British Columbia,
      Vancouver, Canada].

PMID- 27706529
TI  - Antifungal Long-Chain Alkenyl Sulphates Isolated from Culture Broths of the
      Fungus Chaetopsina sp.
AB  - During a high-throughput screening program focused on the discovery and
      characterization of new antifungal compounds, a total of 8320 extracts from
      Fundacion MEDINA's collection were screened against a panel of 6 fungal parasitic
      strains, namely Candida glabrata, Candida krusei, Candida parapsilosis, Candida
      tropicalis, Candida albicans, and Aspergillus fumigatus. A total of 127 extracts
      displayed antifungal properties and, after LC/MS dereplication, 10 were selected
      for further fractionation. Bioassay-guided fractionation from a 1-L fermentation
      of one of these extracts, belonging to the fungus Chaetopsina sp., led to the
      isolation of linoleyl sulphate (1), linolenyl sulphate (2), and oleyl sulphate
      (3) as the compounds responsible for the antifungal activity. These molecules
      were previously described as synthetic products with the ability to produce the
      allosteric inhibition of soybean lipoxygenase and human lipoxygenase.

PMID- 27706530
TI  - Antiviral Activity of Crude Hydroethanolic Extract from Schinus terebinthifolia
      against Herpes simplex Virus Type 1.
AB  - Herpes simplex virus infections persist throughout the lifetime of the host and
      affect more than 80 % of the humans worldwide. The intensive use of available
      therapeutic drugs has led to undesirable effects, such as drug-resistant strains,
      prompting the search for new antiherpetic agents. Although diverse bioactivities
      have been identified in Schinus terebinthifolia, its antiviral activity has not
      attracted much attention. The present study evaluated the antiherpetic effects of
      a crude hydroethanolic extract from the stem bark of S. terebinthifolia against
      Herpes simplex virus type 1 in vitro and in vivo as well as its genotoxicity in
      bone marrow in mammals and established the chemical composition of the crude
      hydroethanolic extract based on liquid chromatography-diode array detector-mass
      spectrometry and MS/MS. The crude hydroethanolic extract inhibited all of the
      tested Herpes simplex virus type 1 strains in vitro and was effective in the
      attachment and penetration stages, and showed virucidal activity, which was
      confirmed by transmission electron microscopy. The micronucleus test showed that
      the crude hydroethanolic extract had no genotoxic effect at the concentrations
      tested. The crude hydroethanolic extract afforded protection against lesions that
      were caused by Herpes simplex virus type 1 in vivo. Liquid chromatography-diode
      array detector-mass spectrometry and MS/MS identified 25 substances, which are
      condensed tannins mainly produced by a B-type linkage and prodelphinidin and
      procyanidin units.

PMID- 27706531
TI  - Direct Oral Anticoagulants and Women.
AB  - Direct oral anticoagulants (DOACs) provide an effective, safe, and convenient
      therapeutic alternative to warfarin and other vitamin K antagonists (VKAs), and
      are now established for a wide range of indications. The use of DOACs in women
      merits special consideration due to two main situations: first, in relation to
      fertility, pregnancy, and lactation in women of reproductive age; second, because
      of their bleeding risk, leading to abnormal uterine and/or other genital tract
      bleeding. This review focuses on these two clinical situations, including
      approaches to management in the context of available information.

PMID- 27706532
TI  - Optimal Anticoagulation for Pregnant Women with Mechanical Heart Valves.
AB  - The prothrombotic state of pregnancy increases the risk of thromboembolic
      complications and death in women with mechanical heart valves (MHVs). Although it
      is accepted that these women must be on therapeutic anticoagulation throughout
      pregnancy, competing maternal and fetal risks, as well as the lack of high
      quality data from prospective studies, make the choice of the optimal method of
      anticoagulation challenging. Vitamin K antagonists (VKAs) are associated with
      fewer maternal complications, but conversely also the lowest live birth rates as
      well as warfarin-related embryopathy and fetopathy. Low-molecular-weight heparin
      (LMWH) does not cross the placenta and is associated with fewer fetal risks but
      more maternal complications. Sequential treatment involving VKAs in the second
      and third trimesters and either low-molecular-weight or unfractionated heparin in
      the first trimester, although appealing is still associated with maternal
      complications, especially around the time of bridging. As absolute equipoise of
      maternal versus fetal wellbeing is unlikely, patient preferences should be
      considered in decision making. A multidisciplinary team including hematologists,
      cardiologists, obstetric physicians, and high-risk obstetricians with expertise
      in the management of pregnant women with cardiac disease is required to optimize
      outcomes. Prospective studies are needed to determine the anticoagulant regimen
      for women with MHVs that provides optimal and acceptable maternal and fetal
      outcomes.

PMID- 27706533
TI  - Neonatal Hemostatic Disorders: Issues and Challenges.
AB  - Neonates form a unique cohort with distinct features associated with the
      hemostatic system compared with older children and adults. The development of the
      human hemostatic system begins around 10 weeks in utero and continues to evolve
      during childhood. This dynamic period termed developmental hemostasis should be
      taken into consideration when diagnosing a neonate with disorders of bleeding or
      thrombosis.

PMID- 27706534
TI  - Topical Tranexamic Acid in Total Knee Arthroplasty Patients with Increased
      Thromboembolic Risk.
AB  - The purpose of this study was to evaluate the efficacy and safety profiles of
      topical tranexamic acid (TXA) in patients undergoing elective total knee
      arthroplasty (TKA) with comorbid conditions precluding them from intravenous (IV)
      TXA use. A total of 104 patients were divided into two groups: 47 in the normal
      risk group and 57 in the high-risk group, with the latter representing those with
      one or more risk factors for venous thromboembolism (VTE). Demographics were
      similar between groups, and there were no differences with regard to
      postoperative changes in hemoglobin (- 3.42 g/dL +/- 1.07 and - 3.68 g/dL +/-
      1.07, p = 0.214), total drain output (630.2 mL +/- 331.6 and 566.9 mL +/- 343.9,
      p = 0.344), postoperative transfusion rate (2.1 and 3.5%, p = 0.675), or total
      number of complications 3 (6.5%) and 5 (8.8%) for the normal- and high-risk
      groups, respectively (p = 0.671). Topical TXA exhibited a similar safety and
      efficacy profile in reducing postoperative blood loss in a group of patients at
      increased thromboembolic risk, without a significant increase in complications or
      thromboembolic events. Topical TXA appears to represent a safe and efficacious
      alternative to IV TXA in patients at high risk for VTE undergoing TKA.

PMID- 27706536
TI  - [Historical Development of the Wool and Colour Plate Tests for Screening for
      Colour Vision Deficiencies in German Speaking Countries].
AB  - Colour vision is a complex visual function that can be affected by congenital
      and/or acquired disorders. The frequency of congenital colour vision deficiencies
      has been investigated in rail and navy staff since the 1870s. Various test
      methods have been developed. Wool tests, flor contrast tests and colour plate
      tests have been used. A published colour plate test, based on Stilling's pseudo
      isochromatic plates in combination with a flor contrast test, has been a common
      screening method for colour vision testing in German-speaking countries. This
      test is intended to detect congenital and acquired colour vision deficiencies in
      a simple and safe manner. More modern options, such as Internet and tablet PC
      have technical limitations, but will increasingly be used for screening for
      colour vision deficiencies.

PMID- 27706535
TI  - [Finite Element Modelling of the Eye for the Investigation of Accommodation].
AB  - Background: Accommodation research increasingly uses engineering methods. This
      article presents the use of the finite element method in accommodation research.
      Material and Methods: Geometry, material data and boundary conditions are
      prerequisites for the application of the finite element method. Published data on
      geometry and materials are reviewed. It is shown how boundary conditions are
      important and how they influence the results. Results: Two dimensional and three
      dimensional models of the anterior chamber of the eye are presented. With simple
      two dimensional models, it is shown that realistic results for the accommodation
      amplitude can always be achieved. More complex three dimensional models of the
      accommodation mechanism - including the ciliary muscle - require further
      investigations of the material data and of the morphology of the ciliary muscle,
      if they are to achieve realistic results for accommodation. Discussion and
      Conclusion: The efficiency and the limitations of the finite element method are
      especially clear for accommodation. Application of the method requires extensive
      preparation, including acquisition of geometric and material data and
      experimental validation. However, a validated model can be used as a basis for
      parametric studies, by systematically varying material data and geometric
      dimensions. This allows systematic investigation of how essential input
      parameters influence the results.

PMID- 27706537
TI  - Colorectal anastomotic dehiscence: an endoscopic modified-stent solution.

PMID- 27706538
TI  - Closure of pancreatic intraductal papillary mucinous carcinoma-colonic fistula
      using an over-the-scope clip.

PMID- 27706539
TI  - Percutaneous transhepatic biliary drainage-assisted, endoscopic ultrasound-guided
      hepaticoduodenostomy for isolated complete right intrahepatic duct obstruction.

PMID- 27706541
TI  - Single-session double-stent placement in concomitant malignant biliary and
      duodenal obstruction with a cautery-tipped lumen apposing metal stent.

PMID- 27706540
TI  - Polyglycolic acid sheet application to prevent esophageal stricture after
      endoscopic submucosal dissection for recurrent esophageal cancer.

PMID- 27706542
TI  - Multi-modality endoscopic management of a submucosal pancreas-perforating gastric
      foreign body.

PMID- 27706543
TI  - Mucosal bridge formation in a patient with esophageal epidermoid metaplasia.

PMID- 27706544
TI  - [Culture-Sensitive Aspects in Diagnostics of Mental Distress in Refugees - Two
      Commented Case Reports].
AB  - High levels of mental disorders, especially PTSD, are commonly known among groups
      of people forced to leave their homeland as a consequence of war-related
      experiences (e. g. armed conflict, torture or persecution). Depending on the
      cultural background the perceptions of illnesses vary, different symptom
      presentation and thereupon different coping strategies respectively expectations
      towards health care services exist. To minimize the danger of misdiagnosis by
      different experts working with refugees in the host countries, a culture
      sensitive diagnostic approach is needed from the beginning. This article
      describes important aspects of culture-sensitive diagnostics by means of 2
      commented case reports. Special focus is set on the aspect of linguistic and in a
      broader sense cultural comprehension between therapist, client and if necessary
      language mediator.

PMID- 27706545
TI  - Rescue therapy of a refractory rectal variceal bleeding in a cirrhotic patient by
      Linton-Nachlas tube and TIPS implantation in combination with variceal
      embolization.
AB  - Background Transjugular intrahepatic portosystemic shunt (TIPS) is considered the
      gold standard for treatment of gastrointestinal variceal bleeding refractory to
      endoscopic therapy in patients with portal hypertension. Clinically relevant
      hemorrhage from rectal varices is less frequent than from other sources, and the
      therapeutic role of TIPS is still ambiguous. Case report A 57-year-old female
      patient was referred to us in December 2015 with severe signs of decompensated
      alcohol-induced liver cirrhosis. During hospitalization, she presented with
      recurrent hematochezia from rectal varices following electrosurgical snare
      removal of a rectal adenoma. Endoscopic treatment with hemoclips, epinephrine and
      fibrin glue injections, and thermocoagulation failed to permanently stop the
      bleeding. Recurrent hemorrhage led to a further deterioration of liver function
      and clinical status of the patient. After a total of 3 endoscopic treatment
      attempts, hemostasis was achieved by transanal placement of a Linton-Nachlas
      balloon tube. Additionally, TIPS implantation with embolization of the rectal
      varices was performed successfully 24 hours after tube insertion, resulting in
      reduction of the portosystemic pressure gradient from 24 to 12 mmHg.
      Subsequently, the patient recovered clinically, hemopressin and catecholamine
      treatment was discontinued, and liver function test as well as serum hemoglobin
      levels improved. No further blood transfusions were required. Conclusion In this
      patient, rescue therapy with balloon compression and TIPS implantation in
      combination with variceal embolization in a cirrhotic patient with refractory
      rectal variceal bleeding was effective. To our knowledge, it is the first
      description of this specific therapeutic approach.

PMID- 27706546
TI  - A liver nodule in a patient transplanted for primary sclerosing cholangitis: an
      interdisciplinary diagnostic approach.
AB  - We report the case of a 53-year-old female patient who was transplanted with the
      liver of a 71-year-old male donor for advanced primary sclerosing cholangitis
      (PSC) and who additionally was diagnosed with a histologically non-classifiable
      colitis shortly before transplantation. Upon follow-up abdominal ultrasound 4
      months after transplantation, a liver lesion measuring 16 * 23 mm was detected in
      the transplanted liver. This lesion had not been noticed immediately after
      transplantation and showed a pattern suspicious for malignancy in contrast
      enhanced ultrasound. In line, a biopsy revealed the presence of a metastasis of
      an adenocarcinoma of colorectal origin, suggesting that a colitis- and PSC
      associated colorectal cancer of the recipient might have been overseen upon the
      initial diagnostic workup. Despite two negative follow-up colonoscopies, this
      hypothesis was further supported by a strong positive signal in projection to the
      cecum in a subsequently performed PET/CT-scan. However, surgical resection of the
      right colon that was performed simultaneously with the atypical resection of the
      liver metastasis only revealed an inflamed diverticulum but no malignancy in the
      resected colon segment. Moreover, cytogenetic and molecular genetic testing on
      the resected specimens clearly attributed the metastasis to the male donor. On
      the one hand, this case underlines the necessity of endoscopic surveillance of
      patients with PSC and/or inflammatory bowel disease as well as the challenges in
      diagnosis of colitis-associated cancer. On the other hand, it shows that the
      acceptance of organs from elderly donors in times of organ shortage might be
      linked to an increased risk of donor transmitted malignancies.

PMID- 27706547
TI  - [Percutaneous paraumbilical embolization of bleeding rectal varices due to portal
      hypertension].
AB  - Introduction Portal hypertension may lead to severe esophageal or rectal variceal
      bleeding. Case report We present a case of a 67-year-old patient presenting with
      recurrent rectal variceal bleeding who was non-responsive to endoscopic
      treatment. We are reporting on an interventional therapeutic approach found in
      interdisciplinary consensus. Discussion Endoscopy, surgery or TIPS (transjugular
      intrahepatic portosystemic shunt) can be performed in patients with
      gastrointestinal bleeding due to portal hypertension in liver cirrhosis. In cases
      not suitable for these treatment options, or in cases where these failed to stop
      the bleeding, radiological percutaneous paraumbilical coil embolization of the
      portal vein collateral feeding the bleeding could be performed. In our case, as
      well as in published cases with embolization of jejunal or esophageal hemorrhage,
      complete stopping of the bleeding could be achieved without further treatment or
      re-bleeding.

PMID- 27706548
TI  - Continued Sex-Differences in the Rate and Severity of Knee Injuries among
      Collegiate Soccer Players: The NCAA Injury Surveillance System, 2004-2009.
AB  - We extend previous analyses and examined sex-differences in the rate and severity
      of knee injuries among collegiate soccer players between 2004 and 2009. Data from
      the National Collegiate Athletic Association Injury Surveillance System (NCAA
      ISS) were used to calculate injury incidence density (ID) per 1 000 athletic
      exposures (AE). Multivariable regression modeling then tested the relation
      between sex and knee injury incidence and severity among all injured soccer
      players, while controlling for contact, setting, and division level, as well as
      for the interactions among these variables. The rate of knee injuries was 1.19
      per 1 000 AEs in women and 0.91 per 1 000 AEs in men (RR=1.31, 95% Wald CI=[1.16,
      1.47]). In the multivariable modeling, women continued to experience
      significantly higher odds of knee injury compared with men (aOR=1.44, 95%
      CI=[1.27,1.63]). Also, the adjusted odds of a knee injury that resulted in
      surgery remained higher in women compared with men (aOR=1.61 (1.00, 2.58), as
      well as the amount of time lost from participation (beta=0.129; p=0.05). Given
      the prominence of soccer play in the United States, continued efforts to evaluate
      and improve knee injury prevention practices and policies may be especially
      important for female players.

PMID- 27706549
TI  - A Multivariate Assessment of Clinical Contributions to the Severity of Perceived
      Dysfunction Measured by the Cumberland Ankle Instability Tool.
AB  - Chronic ankle instability is a common pathological consequence of ankle sprains.
      However, screening tools which assess self-reported dysfunction offer little
      insight into clinical factors which may be useful to improve deficits. The
      purpose of this study was to identify factors that contribute most to self
      reported dysfunction. 93 individuals completed the Cumberland Ankle Instability
      Tool (CAIT), active range of motion, dynamic postural stability assessments, and
      an arthrometer inversion stress test to assess lateral ankle laxity and
      stiffness. Backwards selection linear-regression was used to identify the most
      parsimonious multifactorial model of the predictor variables' ability to predict
      questionnaire score. Ankle sprain history, dorsiflexion in knee flexion, medial
      lateral dynamic postural stability, and inversion laxity talar tilt had the
      highest relationships with the CAIT. When combined in the backwards-regression
      model index, these predictors explained approximately 57% of the variability
      (r=0.76, R2=0.57, F=27.49, p<0.001) of the CAIT. Previous history, laxity, range
      of motion restrictions and balance together contributed to account for almost 60%
      of the variability in the CAIT. Clinical measures may have prognostic value
      assessing the severity of chronic ankle instability and allow clinicians to focus
      on specific deficiencies during rehabilitation programs.

PMID- 27706550
TI  - Precooling does not Enhance the Effect on Performance of Midcooling with Ice
      Slush/Menthol.
AB  - This study investigated whether the combination of internal precooling (PC) and
      internal midcooling (MC cooling during exercise) would enhance performance more
      than MC alone. 9 trained males completed two 30-km cycling trials in a hot and
      humid environment (WBGT: 29+/-0.7 degrees C, 80+/-0.02% relative humidity). For
      30 min before exercise, the subjects sat quietly and drank water at 23 degrees C
      (MC) or 3 degrees C (PC+MC). During the MC and PC+MC time trials, they drank an
      ice-slush/menthol beverage (i. e., 0.025% menthol). Trial time, gastrointestinal
      temperature (Tco ), heart rate (HR), rating of perceived exertion (RPE), thermal
      sensation (TS), and thermal comfort (TC) were assessed. Trial time was not
      significantly different (P>0.05) between MC and PC+MC (3 737+/-552 s and 3 815+/
      455 s). Before exercise, Tco was lower with precooling (37.0+/-0.3 degrees C;
      P<0.02). During exercise, no between-trial differences were noted for Tco, HR,
      RPE, TC or TS, but RPE was significantly lower with PC+MC in the latter stages
      (P<0.05). (1) Cold beverage intake before exercise did not improve the subsequent
      exercise performance with ice-slush/menthol beverage intake, and (2) despite no
      improvement in performance, RPE declined in the latter stages of exercise in the
      condition of PC+MC, suggesting that this combination might be beneficial for
      longer exercise.

PMID- 27706551
TI  - Traditional Periodization versus Optimum Training Load Applied to Soccer Players:
      Effects on Neuromuscular Abilities.
AB  - It is unknown whether traditional periodization of strength-power training
      involving accumulation, transformation and realization blocks is superior to
      other simpler and more practical training schemes. The purpose of this study was
      thus to investigate changes in strength/power/speed characteristics of elite
      soccer players in response to either classic strength-power periodization (TSP)
      or optimum power load (OPL). 23 professional soccer players were randomly
      assigned to TSP or OPL for 6 weeks in-season regular training (3 times per week).
      TSP involved half squats or jump squats, depending on the respective training
      block, while OPL involved only jump squats at the optimum power load. Results
      revealed that both groups presented similar significant (P<0.05) improvements in
      squat one repetition maximum, squat and countermovement jump heights and change
      of direction speed. In addition, although both groups reported significant
      increases in sprinting speed (P<0.05); delta change scores demonstrated a
      superior effect of OPL to improve 10- and 20-m speed. Similarly, OPL presented
      greater delta change in mean propulsive power in the jump squat. Therefore,
      training continuously at the optimum power zone resulted in superior performance
      improvements compared to training under classic strength-power periodization.

PMID- 27706552
TI  - You Can't Always Get What You Want.

PMID- 27706553
TI  - Association between aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism and
      susceptibility to colorectal cancer: a meta-analysis.
AB  - Numerous studies have evaluated the association between Glu504Lys polymorphism in
      the aldehyde dehydrogenase 2 (ALDH2) gene and colorectal cancer (CRC) risk.
      However, the specific association remains controversial. To assess the
      relationship between the ALDH2 Glu504Lys polymorphism and CRC, we conducted a
      comprehensive meta-analysis of five case-control studies comprising 1664 patients
      with CRC and 2777 controls. The results of this meta-analysis showed that the
      ALDH2 Glu504Lys polymorphism was associated with a significantly reduced risk of
      CRC [Lys/Lys vs Glu/Glu: odds ratio (OR) = 0.95, 95% confidence interval (CI) =
      0.58-1.54; Glu/Lys vs Glu/Glu: OR = 0.85, 95%CI = 0.75-0.97; dominant model: OR =
      0.86, 95%CI = 0.76-0.98; recessive model: OR = 1.00, 95%CI = 0.62-1.61]. No
      significant heterogeneity or publication bias was observed in our meta-analysis.
      Based on the statistical data, our meta-analysis indicates that the ALDH2
      Glu504Lys polymorphism is associated with reduced risk of developing CRC.

PMID- 27706554
TI  - Upregulation of ICAM-1 and IL-1beta protein expression promotes lung injury in
      chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a devastating lung disorder
      characterized by sustained airway flow restriction that is not fully reversible.
      The precise pathogenic mechanisms are unknown, but it is clear that cigarette
      smoking and chronic inflammatory stimulation are the major causes of COPD. Lung
      inflammation associated with COPD involves multiple cytokines, aggregation, and
      activation of neutrophils in the airway and lung tissue, and release of proteases
      and oxygen free radicals. In this study, a rat model of COPD was established by
      daily cigarette smoke exposure plus endotoxin treatment (the experimental group).
      Respiratory curves were recorded by the BL-420 biological signal collecting and
      processing system. Furthermore, the contents of inflammatory mediators,
      intercellular adhesion molecular (ICAM)-1 and interleukin (IL)-1beta, in
      bronchoalveolar lavage fluid (BALF) were determined by enzyme linked
      immunosorbent assay for experimental, smoke-exposed only (control), and untreated
      (blank) rat groups. Protein expression levels of ICAM-1 and IL-1beta in the lung
      tissue were also compared among groups by the immunohistochemical streptavidin
      peroxidase method. The COPD model rats exhibited severe dyspnea and lung
      inflammation as evidenced by significantly prolonged expiratory duration, higher
      respiratory rate, elevated ICAM-1 and IL-1beta in BALF, and higher ICAM-1 and IL
      1beta protein expression in lung tissue compared to control and blank group rats.
      Chronic cigarette smoke exposure plus endotoxin is a feasible and reliable model
      of COPD that recapitulates many clinical signs and pathogenic responses. ICAM-1
      and IL-1beta upregulation are possible early contributors to COPD-associated
      inflammatory lung injury.

PMID- 27706555
TI  - Expression and clinical significance of the obesity-related gene TNFAIP9 in obese
      children.
AB  - To investigate the expression of tumor necrosis factor-alpha inducible protein 9
      (TNFAIP9) gene in obese children and its clinical significance, 36 simple obese
      children and 17 non-obese children were recruited as research subjects. The
      adipose tissue was obtained by abdominal operation. The expression of TNFAIP9 was
      detected using real-time fluorescence quantitative polymerase chain reaction and
      western blot. The relationship between the expression of TNFAIP9 and blood lipid,
      blood glucose, and obesity indexes was analyzed. The levels of TNFAIP9 mRNA and
      protein in obese children were significantly lower than those in the control
      group (P < 0.05). The waist circumference (wc), body mass, body mass index (BMI),
      fat, total cholesterol (TC), triglyceride (TG), low-density lipoprotein
      cholesterol (LDL-C), insulin resistance index (HOMA-IR), and endothelin (ET) in
      obese children were significantly higher than those in the control group. The
      level of high-density lipoprotein cholesterol (HDL-C) was significantly lower
      than that in the control group (P < 0.05). The level of TNFAIP9 protein was
      negatively correlated with the wc, body mass, BMI, fat, TC, TG, LDL-C, HOMA-IR,
      and ET (P < 0.05) and was positively correlated with the level of HDL-C (P <
      0.05). In conclusion, the expression of TNFAIP9 significantly decreased in the
      adipose tissue of obese children, and its levels are closely related to blood
      lipid level, insulin resistance, and obesity.

PMID- 27706556
TI  - Developmental expression of LTbetaR and differential expression in Escherichia
      coli F18 resistant/sensitive piglets.
AB  - We analyzed LTbetaR mRNA expression in piglets from birth to weaning and compared
      the differential expression between Escherichia coli F18-resistant and sensitive
      populations to determine whether this gene could be used as a genetic marker for
      E. coli F18 resistance. Sutai piglets of different age groups (8, 18, 30, and 35
      days; N = 4 each) and piglets demonstrating resistance/sensitivity to E. coli F18
      were used. LTbetaR expression levels were determined by real-time PCR. The
      LTbetaR expression levels in the lymph node, duodenum, and jejunum were
      significantly higher in 8-day-old piglets than in the other age groups (P <
      0.01), and the expression levels were significantly higher in the lungs of 8-day
      old piglets than in 35-day-old piglets (P < 0.01) and 30 day-old piglets (P <
      0.05). In liver tissue, the expression level was significantly higher in the 35
      day-old piglets than in other age groups (P < 0.01). In the stomach tissue, the
      expression level was significantly higher in 35-day-old piglets than in 18-day
      old piglets (P < 0.05). LTbetaR expression in the lymph nodes was significantly
      higher in the resistant group than in the sensitive group (P < 0.01), but there
      was no significant difference in the other tissues (P > 0.05). These results
      indicate that 8 days after birth is a crucial stage in the formation of mesentery
      lymph nodes and immune barriers in pigs, and increased expression of LTbetaR may
      be beneficial for developing resistance to E. coli F18.

PMID- 27706557
TI  - Investigating genetic diversity in sapucaia using inter simple sequence repeat
      markers.
AB  - Sapucaia is a tree species originating from the Brazilian Amazon and is widely
      distributed in Brazil, especially in the mid-north region (Piaui and Maranhao
      states). Its seeds are rich in calories and proteins, and possess great potential
      for commercialization. Little is known about the genetic variability in the
      germplasm of most Lecythis species. Here, 11 inter-simple sequence repeat primers
      were used to estimate the genetic variability among 17 accessions, and to
      determine the levels of genetic variation and the standards of population
      structure in sapucaia. The accessions were obtained from the active germplasm
      bank (AGB) of Embrapa Meio-Norte, Teresina, PI, Brazil, and corresponded to four
      occurrence areas. Ninety-six loci were analyzed among the studied individuals.
      High variation was found at the species level, where the percentage of
      polymorphic bands was 94.79%, Nei's genetic diversity (h) was 0.3110, and
      Shannon's index (I) was 0.4732. In the analyzed populations, the percentage
      polymorphism ranged from 20.83 to 94.79%, Nei's genetic diversity ranged from
      0.0863 to 0.2969, and Shannon's index ranged from 0.1260 to 0.4457. Significant
      genetic differentiation was detected among the populations (PhiST = 10.66%);
      however, the greatest genetic differentiation was found within the populations
      (89.34%), between which there was an intermediate level of gene flow (Nm = 1.10).
      Accessions BGS 2 and BGS 4 were the most divergent, whereas accessions BGS 14 and
      BGS 15 were the most similar. Therefore, sapucaia analyzed from the AGB present
      an elevated level of genetic diversity and may have potential use in genetic
      breeding programs.

PMID- 27706558
TI  - De novo transcriptome analysis of tobacco seedlings and identification of the
      early response gene network under low-potassium stress.
AB  - Tobacco is an economically important crop, and its potassium content can greatly
      affect the quality of tobacco leaves. However, the molecular mechanism involved
      in potassium starvation in tobacco has not been elucidated to date. In this
      study, Illumina (Solexa) sequencing technology was used to analyze the
      transcriptome of tobacco seedlings under low-potassium stress for 6, 12, and 24
      h. After analysis, 107,824 assembled unigenes were categorized into 57 GO
      functional groups, and 31,379 unigenes (29.08%) were clustered into 25 COG
      categories. A total of 9945 genes were classified into 233 KEGG pathways, and
      15,209 SSRs were found among the 107,824 unigenes. Between the two samples, 1034
      genes were differentially expressed. Twelve randomly selected gene expression
      levels were analyzed by quantitative RT-PCR, and the results were highly
      consistent with those obtained by Solexa sequencing. Our results provide a
      comprehensive analysis of the gene-regulatory network of tobacco seedlings under
      low-potassium stress.

PMID- 27706559
TI  - Characterization and molecular epidemiology of extensively prevalent nosocomial
      isolates of drug-resistant Acinetobacter spp.
AB  - Acinetobacter sp isolates deserve special attention once they have emerged
      globally in healthcare institutions because they display numerous intrinsic and
      acquired drug-resistance mechanisms. This study assessed the antibiotic
      susceptibility profile, the presence of the genetic marker blaOXA-23, and the
      clonal relationship among 34 nosocomial isolates of Acinetobacter spp obtained at
      a hospital in southeastern Brazil. Antibiotic sensitivity analysis was performed
      by the standard disc-diffusion method. All isolates were found to be extensively
      resistant to several drugs, but sensitive to polymyxin B. A polymerase chain
      reaction (PCR) assay was used to detect the blaOXA-23 gene, which is associated
      with carbapenem resistance. The genetic profile and the clonal relationship among
      isolates were analyzed via enterobacterial repetitive intergenic consensus (ERIC)
      PCR. The Acinetobacter spp were divided into four groups with 22 distinct genetic
      subgroups. ERIC-PCR analysis revealed the genetic diversity among isolates,
      which, despite having a heterogeneous profile, displayed 100% clonality among 56%
      (19/34) of them.

PMID- 27706560
TI  - Canine hepatozoonosis in southeastern Bahia, Brazil.
AB  - In Brazil, canine hepatozoonosis is a tick-borne subclinical hemoparasitosis
      caused by a protozoa Hepatozoon canis and is highly prevalent in dogs in rural
      areas. An epizootiological study was conducted to investigate the prevalence of
      H. canis in the canine population of Itubera, Bahia, and to analyze any
      associated risk factors. Blood samples were collected from 380 dogs and
      determined the presence of the protozoan by performing capillary blood smear and
      polymerase chain reaction (PCR). Epizootiological data were collected by asking
      dog owners to answer a structured questionnaire. H. canis gamonts were not
      detected in the blood smears. However, PCR detected H. canis in 163/380 (42.9%)
      dogs examined. Physical examination and anamnesis indicated 105 (64.4%) positive
      asymptomatic dogs. Hematological alterations were observed in 115 (70.5%)
      infected dogs. No clinical, hematological, or epizootiological variable was found
      to be significantly associated to the infection. In conclusion, the high
      prevalence of H. canis infection in local dogs may be because of the peri-urban
      features of this municipality. Moreover, to the best of our knowledge, this study
      the first study to report H. canis infection in the State of Bahia.

PMID- 27706561
TI  - Genetic association of sequence variation in exon 3 of the swine leukocyte
      antigen-DQA gene with piglet diarrhea in Large White, Landrace, and Duroc
      piglets.
AB  - Piglet diarrhea is one of the primary factors that affects the benefits of the
      swine industry. Recent studies have shown that exon 2 of the swine leukocyte
      antigen-DQA gene is associated with piglet resistance to diarrhea; however, the
      contributions of additional exon coding regions of this gene remain unclear.
      Here, we detected and sequenced variants in the exon 3 region and examined their
      associations with diarrhea infection in 425 suckling piglets using the polymerase
      chain reaction-single-strand conformational polymorphism and sequencing analysis.
      The results revealed that exon 3 of the swine leukocyte antigen-DQA gene is
      highly polymorphic and pivotal to both diarrhea susceptibility and resistance in
      piglets. We identified 14 genotypes (AA, AB, BB, BC, CC, EE, EF, BE, BF, CF, DD,
      DH, GG, and GF) and eight alleles (A-H) that were generated by 14 nucleotide
      variants, eight of which were novel, and three nucleotide deletions. Statistical
      analyses revealed that the genotypes AB and EF were associated with resistance to
      diarrheal disease (P < 0.05), and the genotype DD may contribute to diarrhea
      susceptibility but was unique to Large White pigs (P > 0.05). These results
      elucidate the genetic and immunological background to piglet diarrhea, and
      provide useful information for resistance breeding programs.

PMID- 27706562
TI  - Prevalence of mutations in LEP, LEPR, and MC4R genes in individuals with severe
      obesity.
AB  - Obesity is a major public health concern; despite evidence of high heritability,
      the genetic causes of obesity remain unclear. In this study, we assessed the
      presence of mutations in three genes involved in the hypothalamic leptin
      melanocortin regulation pathway (leptin, LEP; leptin receptor, LEPR; and
      melanocortin-4 receptor, MC4R), which is important for energy homeostasis in the
      body, in a group of patients with severe obesity. For this study, we selected 77
      patients who had undergone bariatric surgery and had a pre-operative body mass
      index (BMI) >35 kg/m2, early onset and a family history of being overweight.
      Candidate genes were screened by direct sequence analysis to search for rare
      genetic variations. The common LEP -2548 G/A polymorphism was also evaluated for
      its influence on the BMI (in obesity patients) and for obesity risk, using a case
      control study involving 117 healthy individuals. Two different non-synonymous
      alterations in MC4R were found in two patients: the p.(Thr112Met), previously
      described in the literature as a probable gene involved in the obesity phenotype,
      and the novel p.(Tyr302Asp) variant, predicted to be pathogenic by in silico
      evaluations and family segregation studies. The LEP -2548 G/A polymorphism was
      not associated with the BMI or obesity risk. In conclusion, we have reported a
      novel mutation in MC4R in a family of Italian patients with severe obesity.
      Screening for MC4R could be important for directing the carriers of mutations
      towards therapy including partial agonists of the MC4R that could normalize their
      appetite and inhibit compulsive eating. Next-generation sequencing could be used
      to clarify the genetic basis of obesity in the future.

PMID- 27706563
TI  - Characterization of the complete mitochondrial genome of Portunus pelagicus with
      implications for phylogenomics.
AB  - This study determined the mitochondrial genome structure of the blue swimming
      crab (Portunus pelagicus), and elucidated its phylogenetic relationships among
      the species within the order Decapoda. The complete mitochondrial genome was
      16,155 bp long, and contained 13 protein-coding genes, 22 transfer RNA genes, 2
      ribosomal RNA genes, and 1 DNA control region. The gene order of the genome was
      the same as that found within the family Portunidae. Twenty-three genes were on
      the heavy strand and 14 were on the light strand. Almost all of the protein
      coding genes were initiated by an ATG codon, except for three genes (ATP6, ND1,
      and ND3) that started with a rare ATT codon. Of the 13 protein-coding genes, 10
      ended with complete TAA or TAG stop codons and three ended with an incomplete T
      codon. Thirteen non-coding regions were identified that ranged from 1 to 30 bp in
      length. Nine overlaps were found, which ranged 1 to 7 bp in length. Phylogenetic
      analyses based on 12 concatenated protein-coding genes revealed that P. pelagicus
      formed a monophyletic group with Portunus trituberculatus, which were in a larger
      group with Callinectes sapidus, while the genera Charybdis and Thalamita formed
      another group. These two groups clustered together and grouped with the genus
      Scylla. The phylogenetic analysis supported the inclusion of Charybdis in
      subfamily Portuninae of the family Portunidae, and revealed a close relationship
      between Charybdis and Thalamita. We suggest that Thalamita should also be
      classified into the subfamily Portuninae. The results can be used in the study of
      phylogenetic, population genetic and conservation genetics of P. pelagicus.

PMID- 27706564
TI  - Inclusion of cytoplasmic lineage effect and direct-maternal genetic covariance
      for genetic evaluation of growth traits in Nellore cattle.
AB  - We evaluated the impact of cytoplasmic lineage effects (Lc) for growth traits on
      genetic evaluation, including the genetic covariance between direct and maternal
      effects (sigmaam). Pedigree data from 496,190 Nellore animals and observations on
      birth weight (BW, N = 243,391), weaning weight (WW, N = 431,681), and post
      weaning weight gain adjusted to 345 days (PWG, N = 172,131) were analyzed. Four
      univariate models were used to obtain estimates of (co)variance components using
      the restricted maximum likelihood method in the BLUPF90 program. Model 1 included
      Lc and sigmaam. Model 2 included Lc and sigmaam was set to zero. Model 3 did not
      include Lc. Model 4 did not include Lc and sigmaam was set to zero. These models
      considered the effects of the Lc as random. Phenotypic variance obtained through
      cytoplasmic lineage effects was determined for all traits, ranging from 0.07 to
      0.15, 0.15 to 0.03, and 0.05 to 0.03% for BW, WW, and PWG, respectively, for
      models 1 and 2. Correlations between direct and maternal genetic components were
      positive for WW and negative for BW and PWG. No differences were observed for
      genetic parameter estimates or animal ranking with the inclusion of sigmaam. For
      BW, the likelihood ratio suggested that model 1 best fits the data, while model 4
      was the most appropriate for WW and PWG. Thus, these models are recommended for
      genetic evaluations. Despite the low magnitude of cytoplasmic lineages, this
      effect could predict breeding value and improve the selection of animals for BW
      in this Nellore population.

PMID- 27706565
TI  - Mixed models for selection of Jatropha progenies with high adaptability and yield
      stability in Brazilian regions.
AB  - The aim of this study was to estimate genetic parameters via mixed models and
      simultaneously to select Jatropha progenies grown in three regions of Brazil that
      meet high adaptability and stability. From a previous phenotypic selection, three
      progeny tests were installed in 2008 in the municipalities of Planaltina-DF
      (Midwest), Nova Porteirinha-MG (Southeast), and Pelotas-RS (South). We evaluated
      18 families of half-sib in a randomized block design with three replications.
      Genetic parameters were estimated using restricted maximum likelihood/best linear
      unbiased prediction. Selection was based on the harmonic mean of the relative
      performance of genetic values method in three strategies considering: 1)
      performance in each environment (with interaction effect); 2) performance in each
      environment (with interaction effect); and 3) simultaneous selection for grain
      yield, stability and adaptability. Accuracy obtained (91%) reveals excellent
      experimental quality and consequently safety and credibility in the selection of
      superior progenies for grain yield. The gain with the selection of the best five
      progenies was more than 20%, regardless of the selection strategy. Thus, based on
      the three selection strategies used in this study, the progenies 4, 11, and 3
      (selected in all environments and the mean environment and by adaptability and
      phenotypic stability methods) are the most suitable for growing in the three
      regions evaluated.

PMID- 27706566
TI  - Estimation of genetic parameters and genetic changes for growth characteristics
      of Santa Ines sheep.
AB  - Studying genetic parameters and genetic changes in Santa Ines sheep is important,
      because it is the commonest breed in Brazil. This study obtained genetic data
      from 37,735 pedigree records of lambs over 12 years (2003-2014) from 33 flocks in
      10 Brazilian States; 11,851 records of performance were available. (Co)variance
      components, genetic parameters and breeding values estimates were obtained by
      derivative-free restricted maximum likelihood in a univariate analysis that
      included maternal additive genetic and maternal permanent environmental effects.
      Birth weight, weaning weight, weight at 180 days of age, weight at 270 days of
      age, average daily weight gain in the following states: from birth to weaning,
      from weaning to 6 months, from 6 months to 9 months, and from weaning to 9
      months; presence of hair in fur and leg muscularity were assessed. (Co)variance
      component values increased in the weight traits with age. A significant maternal
      effect was found in the pre-weaned stage that decreased in the post-weaned stage.
      High values were estimated for the maternal permanent environmental effect,
      possibly because of the extensive grassland that was available. High total
      heritability values were estimated for all of the traits evaluated. Significant,
      positive correlations were found between direct and maternal additive genetic
      traits with a gradual decrease as the lambs gained independence from their
      mothers. The genetic trends observed were irregular and incremental. Significant
      genetic variance suggests that direct selection for pre-weaning traits results in
      indirect selection of maternal abilities, and individual selection of any post
      weaning trait results in rapid genetic improvement.

PMID- 27706567
TI  - Cinnamon effectively inhibits the activity of leukemia stem cells.
AB  - Cinnamon is the main component of Sanyangxuedai, which is one of the effective
      traditional Chinese medicines for treating malignancies. Leukemia is a prevalent
      malignant disease that Sanyangxuedai has been used to treat. Although successful
      in several studies, there is a lack of solid evidence as to why Sanyangxuedai has
      an effect on leukemia, and little is known about the underlying mechanisms. In
      this study, the active ingredients of cinnamon were isolated, purified, and
      identified. The transwell transport pool formed with the Caco-2 cell model was
      used to filter the active ingredients of cinnamon by simulating the
      gastrointestinal barrier in vitro. Moreover, the cell morphology, cell cycle
      status, apoptosis status, and antigenic variation of the cell surface antigens
      were observed and measured in K562 cells after treatment with the active
      ingredients of cinnamon. Our results showed that 50-75 MUM was a safe
      concentration of cinnamon extract for treatment of K562 cells for 72 h. The
      cinnamon extract caused growth inhibition of K562 cells. Cinnamon extract seemed
      to arrest the cells at the G1 stage and increased the apoptosis rate
      significantly. Interestingly, cinnamon extract treatment upregulated the
      expression of erythroid and myeloid differentiation antigens and downregulated
      that of the megakaryocytic differentiation antigens in a dose-dependent manner.
      Our findings indicate that cinnamon extract from Sanyangxuedai may be effective
      for treating leukemia.

PMID- 27706568
TI  - Comparison of methods to preserve Rheum palmatum (Polygonaceae) for efficient DNA
      extraction and PCR amplification.
AB  - In this study, we compared the quality of DNA extracted using the modified CTAB
      method, from Rheum palmatum leaves preserved using fourteen different methods,
      including ones used commonly in other species: under ultra-cold (-80 degrees C)
      temperatures, after drying with an absorbent paper, desiccating using a silica
      gel, drying at 60 degrees C, in 70% ethanol, absolute ethanol, 70% ethanol
      supplemented with 50 mM EDTA, SDS-DNA extracting solution, nuclear separation
      buffer, improved NaCl-CTAB solution, TE-buffer, I-solution, or II-solution. DNA
      extracted from fresh leaves was used as the control. The quality of extracted DNA
      was evaluated based on the success of PCR amplification of the ITS2 region and a
      microsatellite marker. DNA was not extracted from samples preserved in the
      nuclear separation buffer and II-solution. The purities of DNA extracted from
      leaves preserved in ultra-cold temperatures, 70% ethanol, and 70% ethanol with 50
      mM EDTA, and after desiccating using a silica gel and drying were higher, and
      comparable to the purity of DNA extracted from fresh leaves, than those of leaves
      preserved using other methods. In the present study, combined with the PCR
      amplifications, the preservation using ultra-cold temperatures, silica gel
      desiccation, or drying, and PCR amplification of the extracted DNA can be used
      for further molecular studies in R. palmatum.

PMID- 27706569
TI  - Development and characterization of microsatellite loci in Excentrodendron
      hsienmu (Chun & How) H.T. Chang& R.H. Miau.
AB  - Microsatellite markers were isolated using dual-suppression-PCR for the
      endangered species Excentrodendron hsienmu (Tiliaceae) to evaluate the genetic
      diversity and population structure of this species. A total of 11 polymorphic
      microsatellite loci were characterized in E. hsienmu. The number of alleles per
      locus ranged from 2 to 9, with an average of 5.27. The expected heterozygosity
      value ranged from 0.053 to 0.780, with an average of 0.568 and the observed
      heterozygosity value ranged from 0 to 0.595, with an average of 0.268. The
      polymorphic information content value ranged from 0.051 to 0.740, with an average
      of 0.521. These newly designed markers will be of great potential significance
      and profound influence in future research related to the genetic diversity,
      population structure, and patterns of gene flow of this species, which will
      contribute to the implementation of conservation and management strategies for
      this species.

PMID- 27706570
TI  - Role of IL-8 gene polymorphisms in glioma development in a Chinese population.
AB  - This case-control study aimed to investigate the role of -251 T>A (rs4073) and 
      781 C>T (rs2227306) polymorphisms in the interleukin-8 (IL-8) gene in the
      development of glioma in a Chinese population. One hundred and twenty-seven
      glioma patients and 284 healthy control subjects were recruited to this study
      between February 2013 and December 2014. The IL-8 -251 T>A (rs4073) and -781 C>T
      (rs2227306) polymorphisms were genotyped by polymerase chain reaction coupled
      with restriction fragment length polymorphism. The patients and control subjects
      were comparable by gender (X2 = 1.24, P = 0.27), tobacco smoking status (X2 =
      0.80, P = 0.37), alcohol consumption status (X2 = 0.97, P = 0.32), and family
      history of cancer (X2 = 1.54, P = 0.22). The age of glioma patients was
      statistically lower than that of control subjects (t = 2.87, P = 0.002). The chi
      square test revealed the lack of any statistically significant differences in the
      genotype distributions of IL-8 rs4073 (X2 = 0.89, P = 0.64) and rs2227306 (X2 =
      2.58, P = 0.28) between the glioma patients and control subjects. Unconditional
      logistic regression analysis revealed that the IL-8 rs4073 and rs2227306 gene
      polymorphisms did not contribute to the development of glioma. In conclusion, we
      determined that there is a lack of evidence suggesting a significant association
      between the IL-8 rs4073 and rs2227306 gene polymorphisms and the development of
      glioma in a Chinese population.

PMID- 27706571
TI  - Effects of Shenkangling intervention on the MAPK pathway in rats with doxorubicin
      induced nephropathy.
AB  - Shenkangling plays a role of Yishenhuoxue effect for the treatment of children
      with nephrotic syndrome. The aim of this study was to investigate the effects of
      Shenkangling intervention on the mitogen-activated protein kinase (MAPK) pathway
      in rats with Adriamycin-induced nephropathy (AN) and its underlying mechanism of
      action. Nephrosis was induced in healthy Sprague-Dawley rats by doxorubicin and
      the rats were untreated or treated with prednisone, simvastatin, Shenkangling, or
      a combination thereof. Using real-time PCR, the mRNA expression levels of
      Chemokine (C-X-C motif) ligand 16 (CXCL16), A Disintegrin and metalloproteinase
      domain-containing protein 10 (ADAM10), and ADAM17 in the renal tissues of these
      rats were found to be decreased by the various treatments compared to those in
      the untreated doxorubicin-induced nephrosis rats. To quantify the activation of
      the MAPK pathway, western blotting was used to detect the phosphorylation levels
      of MAPK pathway-associated proteins (p38, ERK1/2, SAPK/JNK) and nuclear factor
      (NF)-kappaB p65, which were reduced by the various treatments compared to those
      in the untreated doxorubicin-induced rats. Serum levels of transforming growth
      factor (TGF)-beta1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta,
      and IL-6, quantified by ELISA, were decreased by the various treatments compared
      to the levels in the untreated doxorubicin-induced nephrosis rats. The rats
      treated with prednisone, simvastatin, and Shenkangling showed the best outcome.
      The Chinese medicine Shenkangling that is known for nourishing the kidney and
      promoting blood circulation reduced urinary protein levels, increased serum
      albumin levels, and reduced cholesterol levels by reducing the release of CXCL16,
      ADAM10, ADAM17, TGF-beta1, TNF-alpha, IL-1beta, IL- 6, and other inflammatory
      mediators and inhibiting the activation of the MAPK signaling pathway, thereby
      effectively improving the state of nephropathy in AN rats. These results indicate
      that Shenkangling can be used clinically to treat nephropathy.

PMID- 27706572
TI  - Detection of QTLs controlling fast kernel dehydration in maize (Zea mays L.).
AB  - In order to understand the effect of grain moisture of inbred lines at the
      silking and physiological maturity stages on kernel dehydration rate, 59 maize
      inbred lines from six subgroups were selected. Grain moisture was measured and
      QTLs associated with kernel dehydration were mapped. A rapid dehydration
      evaluation and association analysis revealed eight inbred lines with faster
      dehydration rate, including Yuanwu 02, K36, Zhonger/O2, Lo1125, Han 49, Qi 319,
      Hua 160, and PH4CV. A single sequence repeat analysis using 85 pairs detected
      five QTLs with phenotypic variation contribution >=10% in the permanent F2
      generation populations Zheng 58 x S1776 and Chang 7-2 x K1131, which had LOD
      threshold values >= 3 in both 2013 and 2014. The chromosome region of qFkdr7b had
      not previously been reported and is preliminarily identified as a new major QTL.
      A false positive field verification of grain dehydration rate of 53 inbred lines
      indicated that the screening result of the rapid dehydration inbred lines by
      specific amplification with marker Phi114 was most similar to the field
      assessment result, followed by markers Phi127 and Phi029. The rapid dehydration
      lines selected based on primer Phi114 amplification were also similar to the
      field dehydration rate and can thus be used for molecular marker-assisted
      selection. A significant effort is needed to improve stress resistance and
      shorten the growth period via fast kernel dehydration in intermediate materials
      of the inbred lines K36, Zhonger/ O2, Lo1125, Han 49, Hua 160, and PH4CV, and
      further using the selected lines for new combinations.

PMID- 27706573
TI  - Isolation and characterization of polymorphic microsatellite markers in the
      endangered species Bretschneidera sinensis Hemsl.
AB  - Bretschneidera sinensis is an endangered species that is mainly distributed in
      South China. As a tertiary relict and the single species in the
      Bretschneideraceae family, it has a high conservation value. To investigate the
      influence of human disturbance on its mating system, 63 new microsatellites were
      developed using restriction-site-associated DNA sequencing and their
      polymorphisms were tested on 30 samples from one population. Among the 63
      microsatellites, the number of alleles per locus ranged from 2 to 16. The
      observed and expected heterozygosities ranged from 0.133 to 0.967 and from 0.127
      to 0.912, respectively. These microsatellites may be used for studying the mating
      system of B. sinensis as well as the within-population hereditary structure.

PMID- 27706574
TI  - Polymorphisms in ADAMTS4 and ADAMTS5 are not linked to susceptibility to knee
      osteoarthritis in the Turkish population.
AB  - Considering the functions of aggrecanase-1 (ADAMTS4) and -2 (ADAMTS5), which are
      thought to be the two major enzymes responsible for the destruction of aggrecans
      in arthritic diseases, we investigated whether important polymorphisms in the
      ADAMTS4 and ADAMTS5 genes affect osteoarthritis (OA) susceptibility. Our study
      took place in Mugla, Turkey. Ninety-five cases were recruited following OA
      diagnosis (72 women and 23 men), and 80 individuals without any symptoms or
      radiographic signs of OA (56 women and 24 men) were chosen as healthy controls.
      After obtaining DNA from patients and control subjects, ADAMTS4 and ADAMTS5
      genotypes were determined using the ABI Prism StepOnePlus Real-Time system. In
      addition, we categorized patients based on OA grade. There were no significant
      differences in the genotype distributions of the four polymorphisms between the
      groups (P > 0.05). Moreover, ADAMTS4 and ADAMTS5 allele frequencies did not
      differ between OA and control participants (P > 0.05). These findings suggest
      that the ADAMTS4 (rs4233367 and rs11807350) and ADAMTS5 (rs226794 and rs2830585)
      variants examined may not contribute to susceptibility to knee OA in the Turkish
      population. Other gene polymorphisms should be assessed in order to explain
      variations in OA susceptibility.

PMID- 27706576
TI  - DNA barcoding and phylogenetic relationships of Ardeidae (Aves: Ciconiiformes).
AB  - The avian family Ardeidae comprises long-legged freshwater and coastal birds.
      There has been considerable disagreement concerning the intrafamilial
      relationships of Ardeidae. Mitochondrial cytochrome c oxidase subunit I (COI) was
      used as a marker for the identification and phylogenetic analysis of avian
      species. In the present study, we analyzed the COI barcodes of 32 species from 17
      genera belonging to the family Ardeidae. Each bird species possessed a barcode
      distinct from that of other bird species except for Egretta thula and E.
      garzetta, which shared one barcoding sequence. Kimura two-parameter distances
      were calculated between barcodes. The average genetic distance between species
      was 34-fold higher than the average genetic distance within species. Neighbor
      joining and maximum likelihood methods were used to construct phylogenetic trees.
      Most species could be discriminated by their distinct clades in the phylogenetic
      tree. Both methods of phylogenetic reconstruction suggested that Zebrilus,
      Tigrisoma, and Cochlearius were an offshoot of the primitive herons. COI gene
      analysis suggested that the other herons could be divided into two clades:
      Botaurinae and Ardeinae. Our results support the Great Egret and Intermediate
      Egret being in separate genera, Casmerodius and Mesophoyx, respectively.

PMID- 27706575
TI  - Expression and validation of PvPGIP genes for resistance to white mold
      (Sclerotinia sclerotiorum) in common beans (Phaseolus vulgaris L.).
AB  - The interaction between polygalacturonase-inhibiting proteins (PGIPs), produced
      by plants, and endopolygalacturonases (PGs), produced by fungi, limits the
      destructive potential of PGs and can trigger plant defense responses. This study
      aimed to i) investigate variation in the expression of different common bean
      (Phaseolus vulgaris L.) genotypes and its relationship with resistance to white
      mold (Sclerotinia sclerotiorum); ii) determine the expression levels of PvPGIP
      genes at different time points after inoculation with white mold; and iii)
      investigate differences in PvPGIP gene expression between two white mold isolates
      with different levels of aggressiveness. Four bean lines were analyzed, including
      two lines from a recurrent selection for white mold (50/5 and 84/6), one
      resistant line that was not adapted to Brazilian conditions (Cornell 605), and
      one susceptible line (Corujinha). Gene expression was investigated at 0, 1, 2, 3,
      and 5 days after inoculation. The isolate UFLA 03 caused no significant
      difference in the relative expression of any gene examined, and was inefficient
      in discriminating among the genotypes. For the isolate UFLA 116, all of the genes
      were differentially expressed, as they were associated with resistance to white
      mold, and the expressions increased until the third day after inoculation. The
      50/5 line was not significantly different from the Corujinha line for all of the
      genes analyzed. However, this line had a resistance level that was similar to
      that of Cornell 605, according to the straw test. Therefore, the incorporation of
      PvPGIP genes can increase the resistance of lines derived from recurrent
      selection.

PMID- 27706577
TI  - Characterization and identification of ISSR markers associated with oil content
      in sea buckthorn berries.
AB  - Bioactive oils extracted from sea buckthorn (Hippophae rhamnoides) berries
      contain highly nutritional and medicinal compounds; however, the oil contents of
      sea buckthorn berries are very low. Thirteen inter-simple sequence repeat (ISSR)
      primers were used to identify markers associated with oil content of dry pulp in
      51 cultivars and lines, which clustered into three major groups based on 137
      polymorphic markers. Dry pulp oil contents in 45 cultivars and lines in Group I
      ranged from 6.6 to 33.1%; these accessions belonged to H. rhamnoides ssp
      mongolica and its hybrids with H. rhamnoides ssp sinensis. Three lines (H.
      rhamnoides ssp mongolica) in Group II had high dry pulp oil contents (33.7 to
      37.5%), whereas three lines of hybrids in Group III had low dry pulp oil contents
      (10.9 to 17.5%). The dry pulp oil content of H. rhamnoides ssp mongolica (27.2 +/
      0.9%) was higher than that of hybrids (12.0 +/- 1.2%) (P < 0.01). Four ISSR
      markers (881340, 8251000, 817380, and 8071100) had positive association with high
      dry pulp oil content (P < 0.01) using stepwise multiple regression analysis. The
      use of these ISSR markers is a potential strategy to select genotypes with high
      dry pulp oil content and suitable parental combinations for improvement of sea
      buckthorn berries.

PMID- 27706579
TI  - Spermatogenesis in Nesotriatoma bruneri (Usinger 1944) (Hemiptera, Triatominae).
AB  - The Nesotriatoma genus consists of the species N. flavida N. bruneri and N.
      obscura, forming the Flavida complex. Variation in the size and morphological
      differences intraspecific of N. flavida led to the description of N. bruneri. Two
      years later, the same author proposed the synonymization of N. bruneri with N.
      flavida. Only in 1981 the specific status N. bruneri was recovered by means of
      morphological analysis of the genitalia. However, recently by genetic analysis,
      it was suggested that N. bruneri and N. flavida should be again synonymized. As
      Chagas disease has no cure, the main way to minimize the incidence of this
      disease is by vector control. Thus, grouping biological data from these
      hematophagous insects can assist in the development of vector control programs
      and mainly assist in taxonomic issues of synonymization. Thus, this paper
      describes spermatogenesis of N. bruneri. Three adult N. bruneri males were
      cytogenetically analyzed. The meiotic behavior observed for N. bruneri was very
      similar to that observed for the triatomine species with 23 chromosomes: during
      prophase, chromatin compaction was observed, the chromocenter composition was
      characterized (X1, X2 and Y), and the species karyotype was confirmed as 2n = 23
      (20A + X1X2Y), as it was observed for N. flavida. Moreover, it was possible to
      observe anaphase and telophase. Thus, this study describes reproductive aspects
      of N. bruneri in order to contribute to the biological knowledge of these insects
      of epidemiological importance. Furthermore, this corroborates the synonymization
      of N. bruneri with N. flavida.

PMID- 27706578
TI  - Optimization of selective breeding through analysis of morphological traits in
      Chinese sea bass (Lateolabrax maculatus).
AB  - Determining correlations between certain traits of economic importance
      constitutes an essential component of selective activities. In this study, our
      aim was to provide effective indicators for breeding programs of Lateolabrax
      maculatus, an important aquaculture species in China. We analyzed correlations
      between 20 morphometric traits and body weight, using correlation and path
      analyses. The results indicated that the correlations among all 21 traits were
      highly significant, with the highest correlation coefficient identified between
      total length and body weight. The path analysis indicated that total length (X1),
      body width (X5), distance from first dorsal fin origin to anal fin origin (X10),
      snout length (X16), eye diameter (X17), eye cross (X18), and slanting distance
      from snout tip to first dorsal fin origin (X19) significantly affected body
      weight (Y) directly. The following multiple-regression equation was obtained
      using stepwise multiple-regression analysis: Y = -472.108 + 1.065X1 + 7.728X5 +
      1.973X10 - 7.024X16 - 4.400X17 - 3.338X18 + 2.138X19, with an adjusted multiple
      correlation coefficient of 0.947. Body width had the largest determinant
      coefficient, as well as the highest positive direct correlation with body weight.
      At the same time, high indirect effects with six other morphometric traits on L.
      maculatus body weight, through body width, were identified. Hence, body width
      could be a key factor that efficiently indicates significant effects on body
      weight in L. maculatus.

PMID- 27706580
TI  - Mitogenome of Fejervarya multistriata: a novel gene arrangement and its
      evolutionary implications.
AB  - In this study, we determined the complete nucleotide sequence of the
      mitochondrial (mt) DNA of the paddy frog Fejervarya multistriata. mtDNA is 17,750
      bp long and contains 13 protein-coding regions, 2 ribosomal RNA, non-coding
      genes, and 23 tRNA because of the presence of an extra copy of tRNA-Met. The gene
      arrangements among two related species of Fejervarya were compared, and the
      combined mtDNA data were subjected to a phylogenetic analysis. Interestingly, we
      observed a unique translocation of the tRNA-Leu gene, similar to that reported in
      previous studies on two Fejervarya species. Phylogenetic analyses supported the
      classification into two evolutionary clades, Ranidae and Dicroglossidae, as well
      as placement of Hylarana guentheri in the genus Babina. Our results suggested
      that Fejervarya limnocharis and Fejervarya multistriata may be conspecific,
      because of its low pairwise genetic distance. However, these results must be
      further validated with additional analyses.

PMID- 27706581
TI  - The common CARD14 gene missense polymorphism rs11652075 (c.C2458T/p.Arg820Trp) is
      associated with psoriasis: a meta-analysis.
AB  - Recent genetic evidence suggests a robust association of the CARD14 single
      nucleotide polymorphism rs11652075 (c.C2458T/p.Arg820Trp) and other rare
      mutations in this gene with psoriasis. To assess whether combined data support
      the relationship between CARD14 rs11652075 and susceptibility to this disease, we
      conducted a meta-analysis. PubMed (MEDLINE), EMBASE, Web of Science, and the
      Cochrane Library were searched for relevant papers published in English. Pooled
      odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random
      effect models. Heterogeneity between studies was assessed using the Cochran's Q
      and I2 statistics. A total of five published studies, including 32,807 psoriasis
      patients and 45,458 controls, met our inclusion criteria and were included in the
      meta-analysis. The pooled OR of the association between the minor allele of this
      polymorphism and psoriasis was 0.877 (95%CI = 0.834-0.922; P < 0.001). In a
      stratified analysis, pooled ORs relating to European and Asian ancestry were
      0.883 (95%CI = 0.822-0.948) and 0.872 (95%CI = 0.812-0.936), respectively. Those
      calculated for studies with case sample sizes above and below 1000 were 0.912
      (95%CI = 0.870- 0.956) and 0.824 (95%CI = 0.734-0.924), respectively. No
      publication bias was present, and the exclusion of any single dataset did not
      substantially alter the corresponding pooled ORs. Due to the limited data
      available regarding clinical classification of cases and genotypes, subgroup
      stratification by clinical type was not performed. Our results demonstrate a
      significant association between the CARD14 rs11652075 polymorphism and psoriasis.

PMID- 27706582
TI  - Association between the -174 G/C polymorphism of the interleukin-6 gene and
      myocardial infarction risk: a meta-analysis.
AB  - Numerous studies have evaluated the association between the -174 G/C polymorphism
      in the interleukin-6 gene (IL6) and myocardial infarction (MI) risk. However, the
      results from the published studies are inconclusive. The aim of this meta
      analysis was to determine whether the IL6 -174 G/C polymorphism is associated
      with MI risk. A meta-analysis based on nine case-control studies was performed to
      address this issue. No significant associations between IL6 -174 G/C polymorphism
      and MI risk were observed in any of the genetic models (CC vs GG: OR = 1.18,
      95%CI = 0.92-1.52; CG vs GG: OR = 1.09, 95%CI = 0.93-1.27; dominant model: OR =
      1.11, 95%CI = 0.94-1.31; recessive model: OR = 1.10, 95%CI = 0.91-1.33).
      Furthermore, the subgroup analysis by ethnicity did not reveal a significant
      association between the IL6 -174 G/C polymorphism and susceptibility to MI in
      Caucasians. In conclusion, the results indicate that the IL6 -174 G/C
      polymorphism does not contribute to MI risk.

PMID- 27706583
TI  - Association between expression of DNA mismatch repair genes and clinical features
      and prognosis of patients with radical resection of colon cancer.
AB  - The aim of this study was to investigate the clinical significance of the
      expression of DNA mismatch repair (MMR) genes in patients subjected to radical
      surgical removal of colon cancer, as well as their correlation with disease
      prognosis. Ninety stage II and III colon cancer patients who received
      laparoscopic radical resection of colon cancer at our hospital were recruited in
      this study. The expression of hMLH1, hMSH2, hMSH6, and hPMS2 in the resected
      tumor tissues was examined by SP immunohistochemistry, in order to analyze the
      relationship between defective DNA MMR (dMMR) and the clinico-pathological
      features and prognosis of colon cancer. Patients were followed up over a period
      of 5-35 months, and the Kaplan-Meier survival curve was plotted. dMMR was
      confirmed in 27 subjects (30.0%), among whom recurrence with metastasis and death
      was reported in 5 (18.5%) and 2 (7.4%) patients, respectively. The remaining 63
      subjects displayed proficient DNA MMR (pMMR); among these, 19 (30.2%) and 7
      (11.1%) recurrences with metastasis and death were reported, respectively. dMMR
      showed no significant correlation with gender, age, or therapeutic modality (P >
      0.05), but was significantly correlated with the degree of differentiation, tumor
      location, number of resected lymph nodes, presence of ileus, and TNM stage (P <
      0.05). The prognosis of patients with dMMR was better than that of patients with
      pMMR. dMMR serves as a biomarker for the prognosis of stage II/III colon cancers.

PMID- 27706584
TI  - In silico comparative analysis of tylenchid nematode pectate lyases.
AB  - Phytoparasitic nematodes can infect a wide range of crop plants, and cause
      billions of dollars of agricultural losses each year. These parasites represent
      the largest source of biotic stress experienced by plants. The order Tylenchida
      comprises the most important parasitic nematodes, particularly the root-knot and
      cyst nematodes. These parasitic organisms obtain nutrients to support their
      development through complex interactions with their hosts. Plant-parasitic
      nematodes secrete a mixture of cell-wall degrading enzymes to facilitate
      migration through the plant root. Enzymes are secreted that degrade the principal
      cell-wall components, cellulose, hemi-cellulose, or pectin. Pectate lyases are
      important parasitism factors in plant-parasitic nematodes. These enzymes degrade
      polygalacturonic acid, which is a fundamental constituent of pectin of host cell
      walls. Thus, pectate lyases permit the penetration and colonization of plant host
      cells by parasites. Here, we analyzed 22 pectate lyase protein sequences from
      tylenchid nematode species. Our results revealed great variation in the
      isoelectric points of pectate lyases, and groups of acidic and alkaline proteins
      that may have distinct enzymatic activities were identified. Phylogenetic
      analysis also revealed the presence of two main groups of pectate lyases with
      distinct chemical properties. Seven conserved motifs were identified, but only
      five were present in all sequences. Results of the molecular docking analysis
      revealed differences in the predicted interaction sites in the pectate lyases
      from the two groups. These results may provide a theoretical basis for future
      studies of host plant resistance to nematode infection.

PMID- 27706585
TI  - Effect of domestication on microorganism diversity and anaerobic digestion of
      food waste.
AB  - To accomplish the rapid start-up and stable operation of biogas digesters, an
      efficient inoculum is required. To obtain such an inoculum for food waste
      anaerobic digestion, we domesticated dairy manure anaerobic digestion residue by
      adding food waste every day. After 36 days, the pH and biogas yield stabilized
      signifying the completion of domestication. During domestication, the microbial
      communities in the inocula were investigated by constructing 16S rDNA clone
      libraries. We evaluated the effect of the domesticated inoculum by testing batch
      food waste anaerobic digestion with a non-domesticated inoculum as a control. The
      pH and methane yield of the digestion systems were determined as measurement
      indices. Domestication changed the composition and proportion of bacteria and
      archaea in the inocula. Of the bacteria, Clostridia (49.3%), Bacteroidales
      (19.5%), and Anaerolinaceae (8.1%) species were dominant in the seed sludge;
      Anaerolinaceae (49.0%), Clostridia (28.4%), and Bacteroidales (9.1%), in
      domestication sludge. Methanosaeta was the dominant genus in both of the seed
      (94.3%) and domestication (74.3%) sludge. However, the diversity of methanogenic
      archaea was higher in the domestication than in seed sludge. Methanoculleus,
      which was absent from the seed sludge, appeared in the domestication sludge
      (21.7%). When the domesticated inoculum was used, the digestion system worked
      stably (organic loading rate: 20 gVS/L; methane yield: 292.2 +/- 9.8 mL/gVS; VS =
      volatile solids), whereas the digestion system inoculated with seed sludge failed
      to generate biogas. The results indicate that inoculum domestication ensures
      efficient and stable anaerobic digestion by enriching the methanogenic strains.

PMID- 27706586
TI  - Mixed models identify physic nut genotypes adapted to environments with different
      phosphorus availability.
AB  - The aim of this study was to screen physic nut (Jatropha curcas) genotypes that
      differ in their phosphorous (P) use, using mixed models. The experiment was
      conducted in a greenhouse located in the experimental area of the Centro de
      Ciencias Agrarias of the Universidade Federal do Espirito Santo, in Alegre, ES,
      Brazil. The experiment was arranged in a randomized block design, using a 10 x 3
      factorial scheme, including ten physic nut genotypes and two environments that
      differed in their levels of soil P availability (10 and 60 mg/dm3), each with
      four replications. After 100 days of cultivation, we evaluated the plant height,
      stem diameter, root volume, root dry matter, aerial part dry matter, total dry
      matter, as well as the efficiency of absorption, and use. The parameters were
      estimated for combined selection while considering the studied parameters:
      stability and adaptability for both environments were obtained using the harmonic
      mean of the relative performance of the predicted genotypic values. High genotype
      by environment interactions were observed for most physic nut traits, indicating
      considerable influences of P availability on the phenotypic value. The genotype
      Paraiso simultaneously presented high adaptability and stability for aerial part
      dry matter, total dry matter, and P translocation efficiency. The genotype CNPAE
      C2 showed a positive response to P fertilization by increasing both the total and
      aerial part dry matter.

PMID- 27706587
TI  - Usefulness of the HMRPGV method for simultaneous selection of upland cotton
      genotypes with greater fiber length and high yield stability.
AB  - The harmonic mean of the relative performance of genotypic predicted value
      (HMRPGV) method has been used to measure the genotypic stability and adaptability
      of various crops. However, its use in cotton is still restricted. This study
      aimed to use mixed models to select cotton genotypes that simultaneously result
      in longer fiber length, higher fiber yield, and phenotypic stability in both of
      these traits. Eight trials with 16 cotton genotypes were conducted in the
      2008/2009 harvest in Mato Grosso State. The experimental design was randomized
      complete blocks with four replicates of each of the 16 genotypes. In each trial,
      we evaluated fiber yield and fiber length. The genetic parameters were estimated
      using the restricted maximum likelihood/best linear unbiased predictor method.
      Joint selection considering, simultaneously, fiber length, fiber yield,
      stability, and adaptability is possible with the HMRPGV method. Our results
      suggested that genotypes CNPA MT 04 2080 and BRS CEDRO may be grown in
      environments similar to those tested here and may be predicted to result in
      greater fiber length, fiber yield, adaptability, and phenotypic stability. These
      genotypes may constitute a promising population base in breeding programs aimed
      at increasing these trait values.

PMID- 27706588
TI  - Assessment of genetic relationship among Rhododendron cultivars using amplified
      fragment length polymorphism and inter-simple sequence repeat markers.
AB  - Genetic relationships of 17 Rhododendron cultivars, China, were assessed using
      inter-simple sequence repeat (ISSR) and amplified fragment length polymorphism
      (AFLP) markers. A total of 133 bands were obtained using nine selected ISSR
      primers, 129 (96.99%) of which were polymorphic; 267 bands were amplified by four
      AFLP primer pairs, 251 (94.01%) of which exhibited polymorphism. Based on these
      polymorphic products, a cluster analysis revealed similarities between the
      results of the ISSR and AFLP. All of the cultivars were clustered into two major
      branches; one branch contained the same four cultivars, and the other cultivars
      were separated into different groups in the other branch. The cluster results
      showed that the genetic relationships of the 17 cultivars were partly related to
      their morphological characteristics, particularly the flowering phase. Therefore,
      the results of this study support the classification of Rhododendron cultivars
      according to flowering phase. In addition, the cluster results can be used to
      select suitable parents for breeding.

PMID- 27706589
TI  - Heterogeneous evolution of Ty3-gypsy retroelements among bamboo species.
AB  - Ty3-gypsy long-terminal repeat retroelements are ubiquitously found in many plant
      genomes. This study reports the occurrence of heterogeneous Ty3-gypsy
      retroelements in four representative bamboo species: Phyllostachys heterocycla
      (Carr.) Mitford cv. pubescens, P. heterocycla (Carr.) Mitford cv. heterocycla,
      Dendrocalamopsis oldhami, and Pleioblastus fortunei. Using degenerate
      oligonucleotide primers corresponding to the conserved domains of reverse
      transcriptase (rt) genes of Ty3-gypsy retroelements, 165 distinct sequences were
      amplified from genomic DNA. The length of the nucleotide sequences varied from
      366 to 438 bp. The sequences demonstrated a high heterogeneity, with homology
      ranging from 52.2 to 99.8%. A phylogenetic tree was constructed, including
      Arabidopsis thaliana and Oryza sativa. Bamboo Ty3-gypsy sequences formed three
      distinct retroelement clusters (gypsy I-III). Further analysis indicated that
      there were not only nearly identical Ty3-gypsy retroelements found in distantly
      related species, but also highly diverse Ty3-gypsy retroelements observed in
      closely related species. The results of this study provide genetic and
      evolutionary information about the bamboo genome that could contribute to further
      studies of repetitive elements in bamboo as well as in other species.

PMID- 27706590
TI  - Development of two novel specific SCAR markers by cloning improved RAPD fragments
      from the medicinal mushroom Ganoderma lucidium (Leysser: Fr) Karst.
AB  - Development of sequence-characterized amplified region (SCAR) markers from random
      amplified polymorphic DNA (RAPD) fragments is a valuable molecular approach for
      the genetic identification of different species. By using SCAR markers, molecular
      analysis is reduced to a simple polymerase chain reaction (PCR) analysis using
      primers designed from the amplicon sequence of RAPD. In this study, the DNA
      fragments from an improved RAPD amplification of Ganoderma species were cloned
      into a pGM-T vector; positive clones were identified by PCR amplification and
      enzymatic digestion, and finally, DNA fragments were sequenced using the Sanger
      sequencing method for developing the SCAR markers. Two SCAR markers, named LZ4-1
      with 534 nucleotides, and LZ5-2 with 337 nucleotides were identified, which are
      specific to Ganoderma lucidium (Leysser: Fr) Karst species. BLAST of these two
      nucleotide sequences in the GenBank database showed no identity to other species.
      We deposited these sequences into the GenBank database (LZ4-1 accession No.
      KM391933, LZ5-2 accession No. KM391934). PCR assays confirmed them as novel
      molecular markers for G. lucidium (Leysser: Fr) Karst, which might be used for
      genetic authentication of adulterant samples. Thus, our study developed two
      specific SCAR markers for identifying and distinguishing the medicinal mushroom
      G. lucidium (Leysser: Fr) Karst from other Ganoderma species.

PMID- 27706591
TI  - Polymorphisms of eNOS, catalase, and myeloperoxidase genes in prostate cancer in
      Turkish men: preliminary results.
AB  - Prostate cancer (PCa) is the most common type of neoplasm in European males.
      Genetic and epigenetic factors contribute to PCa development and progression. In
      this study, we aimed to assess the relationship between PCa and polymorphisms in
      the genes encoding endothelial nitric oxide synthase (eNOS), catalase (CAT), and
      myeloperoxidase (MPO). In total, 193 patients were included in the study.
      Patients were divided into three groups: PCa (78), benign prostate hyperplasia
      (40), and control males (75). The parameters assessed included body mass index
      (BMI), smoking habits, presence of prostatism, prostate-specific antigen (PSA)
      levels, Gleason scores of prostate specimens, as well as polymorphisms in eNOS
      G894T, CAT- 262T, and MPO G-463T genes. BMI and smoking status of controls and
      patient groups showed no significant difference. CAT-262T gene polymorphism was
      found to be homozygous in 35.4% of PCa patients, which was 4.02-fold that in the
      controls (P = 0.006). There was no statistically significant difference in eNOS
      G894T and MPO G-463T gene polymorphisms between any of the groups. In conclusion,
      we found catalase levels to be associated with PCa diagnosis and PSA value. We
      did not find any significant differences between groups for other polymorphisms,
      but we believe that further studies with a large sample size may be needed before
      drawing definite conclusions.

PMID- 27706592
TI  - Balanced reciprocal translocation at amniocentesis: cytogenetic detection and
      implications for genetic counseling.
AB  - Balanced translocation is a common structural chromosomal rearrangement in
      humans. Carriers can be phenotypically normal but have an increased risk of
      pregnancy loss, fetal death, and the transmission of chromosomal abnormalities to
      their offspring. Existing prenatal screening technologies and diagnostic
      procedures fail to detect balanced translocation, so genetic counseling for
      carriers remains a challenge. Here, we report the characteristics of chromosomal
      reciprocal translocation in 3807 amniocentesis cases. Of the 16 detected cases of
      fetal reciprocal translocation, 8 cases (50%) showed positive biochemical marker
      screening; 3 cases (18.75%) were the parental carriers of a chromosomal
      abnormality; 2 (12.5%) were of advanced maternal age, 2 (12.5%) had a previous
      history of children with genetic disorders, and 1 case (6.25%) was associated
      with positive soft markers in obstetric ultrasound. Chromosomes 5 and 19 were the
      most commonly involved chromosomes in balanced translocations. Of the 13 cases
      with fetal balanced translocations, 8 (61.5%) were inherited from a paternal
      chromosome, 3 (23.1%) from a maternal chromosome, and 2 (15.4%) cases were de
      novo. The incidence of balanced translocation at amniocentesis was 0.42%. Male
      carriers of reciprocal chromosome translocation appear to have a higher chance of
      becoming a parent of a child born by normal childbirth than female carriers.

PMID- 27706593
TI  - Number of repetitions for evaluating technological traits in cotton genotypes.
AB  - With the changes in spinning technology, technological cotton traits, such as
      fiber length, fiber uniformity, fiber strength, fineness, fiber maturity,
      percentage of fibers, and short fiber index, are of great importance for
      selecting cotton genotypes. However, for accurate discrimination of genotypes, it
      is important that these traits are evaluated with the best possible accuracy. The
      aim of this study was to determine the number of measurements (repetitions)
      needed to accurately assess technological traits of cotton genotypes. Seven
      experiments were conducted in four Brazilian States (Ceara, Rio Grande do Norte,
      Goias, and Mato Grosso do Sul). We used nine brown and two white colored fiber
      lines in a randomized block design with four replications. After verifying the
      assumptions of residual normality and homogeneity of variances, analysis of
      variance was performed to estimate the repeatability coefficient and calculating
      the number of repetitions. Trials with four replications were found to be
      sufficient to identify superior cotton genotypes for all measured traits except
      short fiber index with a selective accuracy >90% and at least 81% accuracy in
      predicting their actual value. These results allow more accurate and reliable
      results in future researches with evaluating technological traits in cotton
      genotypes.

PMID- 27706594
TI  - Genetic and epigenetic diversity and structure of Phragmites australis from local
      habitats of the Songnen Prairie using amplified fragment length polymorphism
      markers.
AB  - The genetic and epigenetic diversity and structure of naturally occurring
      Phragmites australis populations occupying two different habitats on a small
      spatial scale in the Songnen Prairie in northeastern China were investigated by
      assessing amplified fragment length polymorphisms (AFLPs) and methylation
      sensitive amplified polymorphisms (MSAPs) through fluorescent capillary
      detection. The two groups of P. australis were located in a seasonal waterlogged
      low-lying and alkalized meadow with a pH of 8-8.5 and in an alkaline patch
      without accumulated rainwater and with a pH greater than 10. These groups showed
      high levels of genetic diversity at the habitat level based on the percentage of
      polymorphic bands (90.32, 82.56%), Nei's gene diversity index (0.262, 0.248), and
      the Shannon diversity index (0.407, 0.383). Although little is known about the
      between-habitat genetic differentiation of P. australis on a small spatial scale,
      our results implied significant genetic differentiation between habitats.
      Extensive epigenetic diversity within habitats, along with clear differentiation,
      was found. Specifically, the former habitat (Habitat 1, designated H1) harbored
      higher levels of genetic and epigenetic diversity than the latter (Habitat 2,
      designated H2), and population-level diversity was also high. This study
      represents one of few attempts to predict habitat-based genetic differentiation
      of reeds on a small scale. These assessments of genetic and epigenetic variation
      are integral aspects of molecular ecological studies on P. australis. Possible
      causes for within- and between-habitat genetic and epigenetic variations are
      discussed.

PMID- 27706595
TI  - Genetic diversity in natural populations of mangaba in Sergipe, the largest
      producer State in Brazil.
AB  - Mangaba (Hancornia speciosa Gomes) is found in areas of coastal tablelands in the
      Brazilian Northeast and Cerrado regions. This species has been subjected to
      habitat fragmentation that is mainly due to human activity, and requires
      conservation strategies. The aim of this study was to analyze the structure and
      inter- and intrapopulation genetic diversity of natural populations of H.
      speciosa Gomes using inter-simple sequence repeat (ISSR) molecular markers. A
      total of 155 individuals were sampled in 10 natural populations (ITA, PAC, IND,
      EST, BC, PIR, JAP, BG, NEO, and SANT) in the State of Sergipe, Brazil. Fifteen
      primers were used to generate 162 fragments with 100% polymorphism. Genetic
      analysis showed that the variability between populations (77%) was higher than
      within populations (23%). It was possible to identify five different groups by
      the unweighted pair group method with arithmetic mean and principal coordinate
      analysis, and only one individual (E10) remained isolated. Using ISSR markers it
      was possible to obtain a molecular profile of the populations evaluated, showing
      that these markers were effective and exhibited sufficient polymorphism to
      estimate the genetic variability of natural populations of H. speciosa Gomes.

PMID- 27706596
TI  - Detecting the potential cancer association or metastasis by multi-omics data
      analysis.
AB  - Comprehensive multi-omics data analyses have become an important means for
      understanding cancer incidence and progression largely driven by the availability
      of high-throughput sequencing technologies for genomes, proteomes, and
      transcriptomes. However, how tumor cells from the site of origin of the cancer
      begin to grow in other sites of the body is very poorly understood. In order to
      examine potential connections between different cancers and to gain an insight
      into the metastatic process, we conducted a multi-omics data analysis using data
      deposited in The Cancer Genome Atlas database. By combining somatic mutation data
      along with DNA methylation level and gene expression level data, we applied a
      Bayesian network analysis to detect the potential association among four distinct
      cancer types namely, Head and neck squamous cell carcinoma (Hnsc), Lung
      adenocarcinoma (Luad), Lung squamous cell carcinoma (Lusc), and Skin cutaneous
      melanoma (Skcm). Further validation based on the 'identification of somatic
      signatures' and the 'association rules analysis' confirmed these associations.
      Previous investigations have suggested that common risk factors and molecular
      abnormalities in cell-cycle regulation and signal transduction predominate among
      these cancers. This evidence indicates that our study provides a rational
      analysis and hopefully will help shed light on the links between different
      cancers and metastasis as a whole.

PMID- 27706597
TI  - Epigenetic mechanism of maternal post-traumatic stress disorder in delayed rat
      offspring development: dysregulation of methylation and gene expression.
AB  - Maternal post-traumatic stress disorder (PTSD) increases the risk of adverse
      neurodevelopmental outcomes in the child. Epigenetic alternations may play an
      essential role in the negative effects of PTSD. This study was aimed to
      investigate the possible epigenetic alterations of maternal PTSD, which underpins
      the developmental and behavioral impact. 24 pregnant Sprague-Dawley (SD) rats
      were randomly grouped into PTSD and control groups. Open-field tests (OFTs),
      elevated pull maze (EPM) assays, gene expression profile chip tests, and
      methylated DNA immunoprecipitation sequencing (MeDIP-Seq) were performed on the
      offsprings 30 days after birth. The results showed that PTSD offsprings had lower
      body weights and OFT scores than control offsprings. Enzyme-linked immunosorbent
      assays showed that serotonin receptor (5-HT) and dopamine levels were
      significantly lower in PTSD offsprings than in control offsprings. In contrast,
      corticosterone levels were higher in the PTSD group than in the control group. In
      a comparison of the PTSD group versus the control group, 4,160 significantly
      differentially methylated loci containing 30,657 CpGs were identified; 2,487
      genes, including 13 dysmethylated genes, were validated by gene expression
      profiling, showing a negative correlation between methylation and gene expression
      (R = -0.617, P = 0.043). In conclusion, maternal PTSD could delay the physical
      and behavioral development of offsprings, and the underlying mechanism could
      contribute to changes in neurotransmitters and gene expression, owing to
      dysregulation of whole-genome methylation. These findings could support further
      clinical research on appropriate interventions for maternal PTSD to prevent
      methylation dysregulation and developmental retardation.

PMID- 27706598
TI  - Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with
      an "eye open at birth" phenotype.
AB  - Development of the eyelid requires coordination of the cellular processes
      involved in proliferation, cell size alteration, migration, and cell death.
      C57BL/6J-corneal opacity (B6-Co) mice are mutant mice generated by the
      administration of N-ethyl-N-nitrosourea (100 mg/kg). They exhibit the eyelids
      open at birth phenotype, abnormal round cell shape from tightened F-actin bundles
      in leading edge keratinocytes at E16.5, and gradual corneal opacity with
      neovessels. The tip of the leading edge in B6-Co mice did not move forward, and
      demonstrated a sharp peak shape without obvious directionality. Analysis of the
      biological characteristics of B6-Co mice demonstrated that abnormal migration of
      keratinocytes could affect eyelid development, but proliferation and apoptosis in
      B6-Co mice had no effect. Mutant gene mapping and sequence analysis demonstrated
      that in B6-Co mice, adenosine was inserted into the untranslated regions, between
      3030 and 3031, in the mRNA 3'-terminal of Fgf10. In addition, guanine 7112 was
      substituted by adenine in the Mtap1B mRNA, and an A2333T mutation was identified
      in Mtap1B. Quantitative real-time polymerase chain reaction analysis showed that
      expression of the Hbegf gene was significantly down-regulated in the eyelids of
      B6- Co mice at E16.5, compared to B6 mice. However, the expression of Rock1,
      Map3k1, and Jnk1 genes did not show any significant changes. Abnormal
      keratinocyte migration and down-regulated expression of the Hbegf gene might be
      associated with impaired eyelid development in B6-Co mice.

PMID- 27706599
TI  - MicroRNA-338-3p inhibits glucocorticoid-induced osteoclast formation through
      RANKL targeting.
AB  - The differentiation deficiencies of osteoclast precursors (pre-OCs) may
      contribute to osteoporosis. Research on osteoporosis has recently focused on
      microRNAs (miRNAs) that play crucial roles in pre-OC differentiation. In the
      current study, we aimed to analyze the expression and function of the
      glucocorticoid (GC)-associated miRNA-338-3p (miR-338-3p) in osteoclast formation.
      We found that dexamethasone induced osteoclast differentiation and inhibited miR
      338-3p expression. Overexpression of an miR-338-3p mimic in osteoclast precursor
      cells attenuated GC-induced osteoclast formation and bone resorption, whereas
      inhibition of miR-338-3p reversed these effects. The expression of the nuclear
      factor kappaB ligand RANKL, a potential target gene of miR-338-3p, was inversely
      correlated with miR-338-3p expression in pre-OCs. Furthermore, we demonstrated
      that RANKL was directly regulated by miR-338-3p and re-introduction of RANKL
      reversed the inhibitory effects of miR-338-3p on osteoclast formation and bone
      resorption. Taken together, these findings demonstrate that miR-338-3p may play a
      significant role in GC-induced osteoclast differentiation and function by
      targeting RANKL in osteoclasts.

PMID- 27706601
TI  - Pheno-morphological variation, genetic diversity and population structure of
      Tunisian Echinus Medic (Medicago ciliaris L.).
AB  - Medicago ciliaris L., considered as a valuable genetic resource, is a good
      candidate for the improvement of marginal or degraded lands with low fertility or
      high salinity. In this study, the pheno-morphological and genetic diversity were
      investigated in 14 Tunisian populations of M. ciliaris for the first time.
      Fourteen morphological traits showed significant differentiation between
      populations and high levels of diversity. Two amplified fragment length
      polymorphism primer combinations (E-AGC/M-CAA; E-AAG/M-CTG) were analyzed using
      an automated capillary electrophoresis system. A total of 528 loci were
      generated, of which 54% were polymorphic. Allelic polymorphism ranged from 0.02
      to 0.5. Significant variation between populations was found for gene diversity,
      mean number of alleles per locus and Shannon index for which mean values were
      0.17, 0.26, and 1.57, respectively. Analysis of molecular variance revealed a
      high rate of genetic variation within populations. Principal component analysis
      and genotypic clustering discriminated M. ciliaris populations according to their
      geographical origin. M. ciliaris clustered into three main groups. The first
      group was associated with high inland and cold areas, the second was defined by
      low areas with mild winters while the third described low coastal areas.
      Similarity of morphological and molecular results indicated that either markers
      could be used for the study of genetic diversity in this species.

PMID- 27706600
TI  - Analysis of the prevalence of polymorphisms in the glutathione S transferase gene
      (GST) in cataract patients from Goiania.
AB  - The aim of this study was to determine the prevalence of polymorphisms in the
      glutathione S-transferase genes GSTM1 and GSTT1 in patients with lens opacity
      (cataract). Peripheral blood samples were obtained from male and female patients
      (N = 23) with cataract. The GSTM1 and GSTT1 polymorphic regions were amplified by
      polymerase chain reaction, and the amplification products were electrophoresed on
      a 2% agarose gel. The obtained bands were by staining with ethidium bromide. The
      results were compared by a chi-square test using the BioEstat software (v.5.0).
      The frequencies of the GSTM1- and GSTT1-null genotypes were higher than those of
      the GSTM1- and GSTT1-present genotypes. The frequency of GSTT1-null genotypes was
      approximately 1.7 times higher than that of GSTM1, which was a statistically
      significant difference (P = 0.0019). Although a consensus remains to be reached
      on the correlation between genetic polymorphisms in GSTs and cataract
      susceptibility, the observations from most scientific studies are similar to
      those reported in this study. Thus, we conclude that the absence of these genes,
      particularly GSTT1, is correlated with the development of lens opacity.

PMID- 27706602
TI  - Characterization and comparison of transgenic Artemisia annua GYR and wild-type
      NON-GYR plants in an environmental release trial.
AB  - The anti-malarial drug, artemisinin, is quite expensive as a result of its slow
      content in Artemisia annua. Recent investigations have suggested that genetic
      engineering of A. annua is a promising approach to improve the yield of
      artemisinin. In this study, the transgenic A. annua strain GYR, which has high
      artemisinin content, was evaluated in an environmental release trial. First, GYR
      plants were compared with the wild-type variety NON-GYR, with regard to
      phenotypic characters (plant height, crown width, stem diameter, germination
      rate, leaf dry weight, 1000-seed weight, leave shape). Second, stress resistance
      in the two varieties (salt, drought, herbicide, and cold resistance) was
      evaluated under different experimental conditions. Finally, gene flow was
      estimated. The results indicated that there were significant differences in
      several agronomic traits (plant height, stem diameter, and leave dry weight)
      between the transgenic GYR and NON-GYR plants. Salt stress in transgenic and
      control plants was similar, except under high NaCl concentrations (1.6%, w/w).
      Leaf water, proline, and MDA content (increased significantly) were significantly
      different. Transgenic A. annua GYR plants did not grow better than NON-GYR plants
      with respect to drought and herbicide resistance. The two varieties maintained
      vitality through the winter. Third, gene flow was studied in an environmental
      risk trial for transgenic GYR. The maximum gene flow frequency was 2.5%, while
      the maximum gene flow distance was 24.4 m; gene flow was not detected at 29.2 m
      at any direction. Our findings may provide an opportunity for risk assessment in
      future commercialization of transgenic A. annua varieties.

PMID- 27706603
TI  - White mold resistance-associated quantitative trait loci in the Jalo x Small
      White common bean population.
AB  - We aimed to identify simple sequence repeat (SSR) markers linked to quantitative
      trait loci (QTLs) associated with white mold resistance in a segregating
      population derived from a cross between common bean cultivars Jalo and Small
      White, in the Southern State of Minas Gerais. Parents were crossed to obtain the
      F2 generation of 190 plants. From these, F2:3 and F2:4 progenies were obtained
      for phenotypic evaluation. DNA was extracted from F2 plants and parents for
      genotyping with SSR primers. For phenotypic assessment by the straw test, we used
      190 F2:3 progenies and six lines in a triple-lattice design of 14 x 14 m. Nine
      trials were conducted for phenotyping by the oxalic acid method to evaluate 177
      F2:4 progenies, in addition to the two parents and two common treatments
      represented by the Jalo and Corujinha lines. The experimental design for the
      oxalic acid method was completely randomized with three replicates. Adjusted
      means of evaluations related to F2:3 and F2:4 were used to identify QTLs by using
      the moving away method from the marker under Bayesian analysis. The markers
      GATS91, BM197, and X60000 stood out with high heritability and with effects on
      disease reduction by the straw test; therefore, these markers are promising for
      selection. The markers BM183, BM189, and SSR-IAC143 were associated with the QTLs
      identified by oxalic acid, providing greater effects in white mold resistance
      with high heritability. Based on the oxalic acid and straw test methods, the most
      prominent marker was PVBR189.

PMID- 27706604
TI  - Biplot analysis of strawberry genotypes recommended for the State of Espirito
      Santo.
AB  - Most strawberry genotypes grown commercially in Brazil originate from breeding
      programs in the United States, and are therefore not adapted to the various soil
      and climatic conditions found in Brazil. Thus, quantifying the magnitude of
      genotype x environment (GE) interactions serves as a primary means for increasing
      average Brazilian strawberry yields, and helps provide specific recommendations
      for farmers on which genotypes meet high yield and phenotypic stability
      thresholds. The aim of this study was to use AMMI (additive main effects and
      multiplicative interaction) and GGE biplot (genotype main effects + genotype x
      environment interaction) analyses to identify high-yield, stable strawberry
      genotypes grown at three locations in Espirito Santo for two agricultural years.
      We evaluated seven strawberry genotypes (Dover, Camino Real, Ventana, Camarosa,
      Seascape, Diamante, and Aromas) at three locations (Domingos Martins, Iuna, and
      Muniz Freire) in agricultural years 2006 and 2007, totaling six study
      environments. Joint analysis of variance was calculated using yield data (t/ha),
      and AMMI and GGE biplot analysis was conducted following the detection of a
      significant genotypes x agricultural years x locations (G x A x L) interaction.
      During the two agricultural years, evaluated locations were allocated to
      different regions on biplot graphics using both methods, indicating distinctions
      among them. Based on the results obtained from the two methods used in this study
      to investigate the G x A x L interaction, we recommend growing the Camarosa
      genotype for production at the three locations assessed due to the high frequency
      of favorable alleles, which were expressed in all localities evaluated regardless
      of the agricultural year.

PMID- 27706605
TI  - In silico characterization of 1,2-diacylglycerol cholinephosphotransferase and
      lysophospha-tidylcholine acyltransferase genes in Glycine max L. Merrill.
AB  - The enzymes 1,2-diacylglycerol cholinephosphotrans-ferase (CPT) and
      lysophosphatidylcholine acyltransferase (LPCAT) are important in lipid metabolism
      in soybean seeds. Thus, understand-ing the genes that encode these enzymes may
      enable their modification and aid the improvement of soybean oil quality. In
      soybean, the genes encoding these enzymes have not been completely described;
      there-fore, this study aimed to identify, characterize, and analyze the in silico
      expression of these genes in soybean. We identified two gene models encoding CPT
      and two gene models encoding LPCAT, one of which presented an alternative
      transcript. The sequences were positioned on the physical map of soybean and the
      promoter regions were analyzed. Cis-elements responsible for seed-specific
      expression and responses to biotic and abiotic stresses were identified. Virtual
      expression analysis of the gene models for CPT and LPCAT indicated that these
      genes are expressed under different stress conditions, in somatic embryos during
      differentiation, in immature seeds, root tissues, and calli. Putative ami-no acid
      sequences revealed the presence of transmembrane domains, and analysis of the
      cellular localization of these enzymes revealed they are located in the
      endoplasmic reticulum.

PMID- 27706606
TI  - Detecting multiple DNA human profile from a mosquito blood meal.
AB  - Criminal traces commonly found at crime scenes may present mixtures from two or
      more individuals. The scene of the crime is important for the collection of
      various types of traces in order to find the perpetrator of the crime. Thus, we
      propose that hematophagous mosquitoes found at crime scenes can be used to
      perform genetic testing of human blood and aid in suspect investigation. The aim
      of the study was to obtain a single Aedes aegypti mosquito profile from a human
      DNA mixture containing genetic materials of four individuals. We also determined
      the effect of blood acquisition time by setting time intervals of 24, 48, and 72
      h after the blood meal. STR loci and amelogenin were analyzed, and the results
      showed that human DNA profiles could be obtained from hematophagous mosquitos at
      24 h following the blood meal. It is possible that hematophagous mosquitoes can
      be used as biological remains at the scene of the crime, and can be used to
      detect human DNA profiles of up to four individuals.

PMID- 27706607
TI  - Effects of sodium lactate Ringer's injection on transfection of human protein
      kinase C-alpha antisense oligonucleotide in A549 lung cancer cells.
AB  - In the present study, we evaluated the effects of four solutions [Dulbecco's
      modified Eagle's medium (DMEM), sodium lactate Ringer's injection (SLRI),
      phosphate-buffered saline (PBS), and NaCl] on the transfection of the human
      protein kinase C-a antisense oligonucleotide (PKC-a ASO) aprinocarsen in human
      lung carcinoma A549 cells. Specifically, SLRI, DMEM, PBS, or NaCl were used as
      the growth solutions for A549 cells, and OPTI-MEM was used as the PKC-a ASO
      diluent for transfection. Additionally, SLRI, DMEM, PBS, or NaCl were used as
      both the growth solutions and diluents for transfection. The cell viability and
      transfection efficiency were determined. The results demonstrated that when SLRI
      was used as either the growth solution or both the growth solution and diluent
      for aprinocarsen transfection in A549 cells, the effects were close to the best
      effects observed with DMEM as the growth solution and OPTI-MEM as the diluent,
      which supported the transfection of aprinocarsen into the cells. Moreover, SLRI
      resulted in higher transfection efficiency than those of PBS and NaCl. In in
      vitro experiments, aprinocarsen effectively induced apoptosis in A549 cells. In
      conclusion, SLRI may replace PBS or NaCl in clinical trials as a transfection
      solution readily accepted by the human body. To our knowledge, this is the first
      report demonstrating the use of SLRI as a transfection solution in lung-cancer
      cell lines.

PMID- 27706608
TI  - Temporal and spatial expression of Smads and their correlation with YAP1
      expression in sheep.
AB  - The temporal and spatial patterns of Smad and Yes-associated protein 1 (YAP1)
      expression were investigated in skeletal muscle (gastrocnemius muscle and
      extensor digitorum longus) at different growth stages (2 days old, 2 and 6 months
      old) in Hu sheep. Smads were differentially expressed in sheep skeletal muscle,
      with high expression in the gastrocnemius muscle and lower expression in the
      extensor digitorum longus. Expression of Smad2, Smad3, and Smad4 at the 2-day-old
      stage was significantly higher than at other stages (P < 0.05). The expression of
      Smad7 in 2-day-old sheep was lower than in 6-month-old sheep, with the lowest
      levels at 2 months. Smad expression was higher in males than in females at the 2
      day-old stage, and expression in 2- and 6-month-old males was lower than that in
      2-day-old females. Smad3 expression was higher in the 2-day- and 2-month-old
      males than in the females. There was a positive correlation (P < 0.01) between
      YAP1 and Smad2 expression in gastrocnemius muscle at the 2-month-old stage. YAP1
      and Smad4/7 expression were positively correlated (P < 0.01) in extensor
      digitorum longus at the 2-day-old stage. YAP1 expression was negatively
      correlated with Smad7 in the extensor digitorum longus at 6 months. A significant
      difference between Smad2 and Smad3 (P < 0.01) expression in muscle was observed,
      consistent with Smad3 and Smad4 expression, indicating that these inhibit
      transforming growth factor-beta signaling in the same way. There was a positive
      correlation (P < 0.01) between YAP1 and MSTN expression, suggesting that YAP1
      participates in muscle growth in sheep.

PMID- 27706609
TI  - Correlation of the TCF7L2 (rs7903146) polymorphism with an enhanced risk of type
      2 diabetes mellitus: a meta-analysis.
AB  - Increasing evidence has demonstrated that a transcription factor 7-like 2
      (TCF7L2) polymorphism (rs7903146) is significantly associated with type 2
      diabetes mellitus (T2DM); however, limited sample size and variance of ethnicity
      in the studies investigating this association have led to conflicting reports
      regarding its role. Therefore, a comprehensive meta-analysis was conducted to
      quantitatively assess the association between the TCF7L2 polymorphism (rs7903146)
      and T2DM including published case-control studies in global populations. We
      searched the PubMed, EMbase, CNKI, and Wanfang databases for publications that
      studied correlation between TCF7L2 polymorphism (rs7903146) and risk of T2DM.
      Thirty-six studies from 30 eligible papers were identified. After data extraction
      and reference quality assessment, summary odds ratio and 95% confidence intervals
      (95%CI) of the TCF7L2 (rs7903146) polymorphism were calculated and combined using
      the fixed-effect model. Hardy-Weinberg equilibrium was evaluated to determine
      selection bias of the control subjects. Heterogeneity among studies was examined
      using the Q-test and the I2 test. Publication bias in studies was assessed using
      Begg's plots and the Egger test. The results showed that the rs7903146 T allele
      of the TCF7L2 gene was positively correlated with an enhanced risk of T2DM in the
      allelic, heterozygote, homozygote, dominant, and recessive models, with odds
      ratios of 1.35 (T vs C, 95%CI = 1.31-1.39), 1.32 (CT vs CC, 95%CI = 1.27-1.38),
      1.74 (TT vs CC, 95%CI = 1.63-1.87), 1.40 (TT+CT vs CC, 95%CI = 1.35-1.46), and
      1.59 (TT vs CT+CC, 95%CI = 1.49-1.69), respectively. No obvious publication bias
      was observed using the Egger linear test.

PMID- 27706610
TI  - Improved protocol for extracting genomic DNA from frozen formalin-fixed tissue
      resulting in high-quality whole mtDNA.
AB  - Formalin fixation and paraffin embedding is widely used for convenient and long
      term storage of tumor tissue and precious sources to perform genetic studies.
      However, DNA fragmentation is one of the major flaws of genomic DNA isolation
      from formalin fixation tissues, which limits its further usage. Here, we present
      an improved method for isolating high-quality genomic DNA from formalin fixation
      tissue. We obtained high-quality genomic DNA of more than 20 kb from samples
      frozen for more than 2 years. Furthermore, to verify DNA quality, the whole
      mitochondrial DNA (mtDNA) genomes from the normal and tumor tissue of the same
      patient were successfully amplified with two overlapping PCR fragments comprising
      more than 8379 bp in length for each fragment. In addition, the whole genomes
      were sequenced with a 48-well based primer panel in order to avoid potential
      sequencing errors from artificial recombination, which was further confirmed with
      an mtDNA phylogenetic strategy. Our improved DNA extraction method from formalin
      fixation tissue and sequencing strategy for entire mtDNA genomes will generate
      unambiguous sequence analysis results for clinical samples.

PMID- 27706611
TI  - Association of IL-1alpha gene polymorphism with susceptibility to type 1 diabetes
      in Chinese children.
AB  - The interleukin-1alpha (IL-1alpha) gene appears to play a role in the
      pathogenesis of type 1 diabetes (T1D). Therefore, the aim of this study was to
      investigate the contribution of the IL-1 rs1800587 gene polymorphism to
      susceptibility to T1D in Chinese children. This case-control study included 332
      Chinese children with T1D and 332 healthy controls. Identification of genetic
      variants of rs1800587 in the IL-1alpha gene was performed by polymerase chain
      reaction amplification. The IL-1alpha rs1800587 polymorphism demonstrated a
      significant association with T1D risk. The allelic frequency significantly
      differed between the T1D and control groups [odds ratio (OR) = 0.7; 95%
      confidence interval (CI) = 0.52-0.86; P = 0.002]. Furthermore, significant
      differences were observed in the dominant model (CC/CT + TT; OR = 0.6; 95%CI =
      0.46-0.85; P = 0.003). In T1D patients, the prevalence of hypertension in T
      allele carriers was 4.2-fold higher than that in C allele carriers, (95%CI = 2.67
      6.58; P < 0.001). In conclusion, the present study found evidence of a
      significant association between the rs1800587 polymorphism in the IL-1alpha gene
      and T1D.

PMID- 27706612
TI  - Activation of Src tyrosine kinase in esophageal carcinoma cells in different
      regulatory environments and corresponding occurrence mechanism.
AB  - This study aims at observing the expression of activated Src tyrosine kinase in
      esophageal squamous cell carcinoma (ESCC), and exploring the relationship of Src
      tyrosine kinase with the occurrence and progression of ESCC.
      Immunohistochemistry, immunofluorescence, and immunoblotting are employed to
      investigate the expression of Src tyrosine kinase in the ESCC tissue. Cellular
      immunofluorescence is used to measure the expression of activated Src tyrosine
      kinase in TE1 and TE9 cell lines of human ESCC tissues and EPC1-htert and EPC2
      htert cell lines of esophageal epithelial cells. Src tyrosine kinase is
      overexpressed in ESCC tissue and underexpressed in normal esophageal mucosa.
      Furthermore, it is overexpressed in the TE1 and TE9 cell lines of human ESCC
      tissue and underexpressed in the EPC1-htert and EPC2-htert cell lines of
      esophageal epithelial cells. Src tyrosine kinase shows a higher expression in
      human ESCC tissue than in normal esophageal mucosa. The difference is
      statistically significant (P < 0.05). The activation of Src tyrosine kinase plays
      an important role in the occurrence and development of ESCC.

PMID- 27706613
TI  - Dynamic QTL analysis of seed reserve utilization in sh2 sweet corn germination
      stages.
AB  - In this study, dynamic quantitative trait loci (QTL) were mapped in a recombinant
      inbred line (F2:4) population derived from a BF3109 x Q267 cross. This was done
      during the unconditional (4, 7, and 10 days) and conditional (0 to 4, 4 to 7, and
      7 to 10 days) germination stages in sh2 sweet corn. The values of seedling dry
      weight, weight of mobilized seed reserve (WMSR), seed reserve depletion
      percentage (SRDP), seed reserve utilization efficiency (SRUE), and their
      heritability differed across the investigated stages. The heritabilities of these
      traits were lower at 7D/4D and 10D/7D compared with those at the 4- (4D/0D), 7-
      and 10-day (D) developmental stages. WMSR and SRDP were significantly negatively
      correlated with SRUE at the early stage. The unconditional QTL mapping can
      explain the accumulation of genetic effects of seed reserve utilization from the
      starting time, whereas the conditional QTL mapping can reveal genetic expression
      in the time intervals. Fifteen and fourteen additive QTLs were identified by the
      unconditional and conditional mapping, respectively. The number of additive QTLs
      and their effect values varied among the different stages. More additive QTLs
      were found at the later stage (7 to 10 days), based on the conditional mapping
      results. The identification of QTL mapping based on a combination of time
      dependent measurements is important for a better understanding of the genetic
      bases of seed reserve utilization. It is also important for the improvement of
      relevant variety traits for subsequent sweet corn-breeding studies using marker
      assisted selection.

PMID- 27706614
TI  - Characterization of gene methylation in human papillomavirus associated-head and
      neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) has become one of the most common
      forms of cancer worldwide. Hypermethylation-induced silencing of tumor-associated
      gene has been proposed as an important cofactor in cancer pathology. This paper
      aimed to characterize the gene methylation patterns in human papillomavirus (HPV)
      associated-HNSCC. TIMP3 and APC methylation status in neoplastic (N = 92) and non
      neoplastic tissues (N = 92) of HNSCC as well as their association with HPV
      infection were investigated via methylation-specific PCR assays. Results
      indicated that methylation level of TIMP3 was markedly higher in HPV-positive
      tumors as compared with HPV-negative tumors. Both TIMP3 and APC methylation were
      associated with lymph node metastasis and higher clinical stage of tumors.
      Patients with methylation at TIMP3 or APC had worse prognoses as compared to
      those without these alterations. This is the first study that shows a possible
      linkage between HPV infection and APC methylation. Methylation patterns of tumor
      related genes may contribute to different disease prognosis in HNSCC according to
      the HPV infection status.

PMID- 27706615
TI  - HLA-G genetic variants and hepatocellular carcinoma: a meta-analysis.
AB  - Human leukocyte antigen (HLA)-G is a key tolerogenic molecule mainly expressed in
      the placenta and is crucial for implantation of the embryo and immunological
      tolerance of the fetus during pregnancy. However, under pathological conditions,
      such as cancer or viral infections, HLA-G can be expressed in other tissues. The
      gene coding for HLA-G (HLA-G, chromosome 6p21.3) presents numerous polymorphisms,
      some of them influencing its expression. One of the most studied, is the 14 bp
      ins/del (rs371194629) situated at the 3'-UTR of the gene. The insertion is
      thought to stabilize HLA-G mRNA. Different studies have analyzed the role of
      rs371194629 in hepatic injury, with either hepatotropic virus infection (i.e.,
      HBV or HCV) or hepatocellular carcinoma (also induced by viral infection).
      Results from these studies are heterogeneous, differing with ethnicity and
      population age, and the role of rs371194629 is unclear. For these reasons, we
      decided to perform a meta-analysis of these results, concluding that the 14-bp
      ins/del polymorphism does not significantly contribute to hepatic injury.

PMID- 27706616
TI  - Investigation of the role of XRCC1 genetic polymorphisms in the development of
      gliomas in a Chinese population.
AB  - We conducted a study in a Chinese Han population to investigate the role of XRCC1
      gene polymorphisms (Arg399Gln and Arg194Trp) with a risk of susceptibility to
      gliomas. Samples from 115 patients with gliomas and 228 control subjects were
      consecutively collected between March 2012 and December 2014. Genotype analysis
      of XRCC1 Arg399Gln and Arg194Trp was performed using polymerase chain reaction
      restriction fragment length polymorphism assay. All the analyses were performed
      using the SPSS 17.0 software package. We observed that the XRCC1 Arg399Gln and
      Arg194Trp genotype frequencies conformed to the Hardy-Weinberg equilibrium. We
      observed that the Trp/Trp genotype of XRCC1 Arg194Trp was associated with an
      increased risk of glioma when compared to the wild-type genotype (odds ratio (OR)
      = 2.14, 95% confidence interval (CI) = 1.14-3.86, P = 0.03). In the dominant
      model, we found that the Arg/Trp + Trp/Trp genotype of XRCC1 Arg194Trp could
      significantly elevate the susceptibility of developing glioma (OR = 1.79, 95%CI =
      1.07-0.94). However, we observed that the XRCC1 Arg399Gln genetic polymorphism
      did not influence the risk of glioma. In summary, we suggest that the XRCC1
      Arg194Trp genetic polymorphism could be a predictive biomarker for the
      susceptibility to glioma in a Chinese population.

PMID- 27706618
TI  - Identification of key biomarkers involved in osteosarcoma using altered modules.
AB  - The aim of this study was to screen for key biomarkers of osteosarcoma (OS) by
      tracking altered modules. Protein-protein interaction (PPI) networks of OS and
      normal groups were constructed and re-weighted using the Pearson correlation
      coefficient (PCC), respectively. The condition-specific modules were explored
      from OS and normal PPI networks using a clique-merging algorithm. Altered modules
      were identified by a maximum weight bipartite-matching method. The important
      biological pathways in OS were identified by a pathway-enrichment analysis using
      genes from disrupted modules. The most important genes in these pathways were
      selected as key biomarkers. Finally, the mRNA and protein expressions of hub
      genes in OS bone tissues were analyzed using reverse transcription-polymerase
      chain reaction and western blotting, respectively. We identified 703 and 2270
      modules in normal and disease networks, respectively; 150 altered modules were
      identified from among these and explored. We identified 10 important pathways
      based on gene pairs with altered PCC > 1 in the disrupted modules (P < 0.01), and
      PCNA, ATP6V1C2, ATP6V1G3, FEN1, CDC7, and RPA3 (expressed in these pathways) were
      selected as key genes of OS. We observed that these genes (and the proteins they
      encoded) were differentially expressed between normal and OS samples (P < 0.01)
      (excluding ATP6V1C2, whose protein expression did not differ significantly).
      Therefore, we identified 5 gene signatures that may be potential biomarkers for
      the detection and effective therapy of OS.

PMID- 27706617
TI  - Correlation of VCAM-1 expression in serum, cord blood, and placental tissue with
      gestational hypertension associated with fetal growth restriction in women from
      Xingtai Hebei, China.
AB  - The aim of this study was to investigate the expression of vascular adhesion
      molecule (VCAM)-1 in the maternal serum, cord blood, and placental tissue of
      pregnant women from Xingtai, Hebei, with gestational hypertension (GH) combined
      with fetal growth restriction (FGR). A total of 108 patients with GH combined
      with FGR (GH-FGR), 60 patients with GH alone (GH), and 50 healthy pregnant women
      (control) were recruited to this study. VCAM- 1 expression was detected in the
      maternal serum and cord blood by enzyme-linked immunosorbent assay, and in the
      placental tissue by immunohistochemistry. VCAM-1 expression was significantly
      higher in the maternal serum of patients with GH-FGR (164.38 +/- 60.35) and GH
      alone (103.85 +/- 54.47) than in the serum of the control population (46.70 +/-
      21.79; P < 0.05). On the other hand, VCAM-1 expression in the cord blood of GH
      FGR (163.19 +/- 69.46), GH (149.82 +/- 58.20), and control (128.89 +/- 43.59)
      subjects was not significantly different (P > 0.05). Moreover, the VCAM-1
      expression rates were significantly higher and lower in the vascular endothelial
      and trophoblastic cells of the placenta of patients with GH-FGR (74.71 and 56.1%)
      and GH (72.98 and 55.36%), respectively, compared to those in the control
      subjects (46.48 and 95.11%). Therefore, we concluded that VCAM- 1 plays an
      important role in the development and generation of GH. Additionally, the low
      VCAM-1 expression in the trophoblastic cell could be correlated to the
      pathogenesis and progression of GH.

PMID- 27706619
TI  - Assessing the association between EFEMP1 rs3791679 polymorphism and risk of
      glioma in a Chinese Han population.
AB  - In this study, we assessed the association between the EFEMP1 rs3791679
      polymorphism and glioma risk in a Chinese Han population. A total of 94 glioma
      patients and 206 healthy controls who conformed to the inclusion and exclusion
      criteria were recruited from Baogang Hospital between March 2012 and October
      2014. The EFEMP1 rs3791679 gene polymorphism was assessed using a polymerase
      chain reaction-restriction fragment length polymorphism assay and the results
      were statistically analyzed using SPSS Statistics 17.0. The results of
      unconditional logistic regression analysis revealed that the GG genotype of
      EFEMP1 rs3791679 was positively correlated with increased susceptibility to
      glioma (adjusted OR = 2.09, 95%CI = 1.21-7.81). Moreover, the GG genotype of
      EFEMP1 rs3791679 was correlated with higher risk of glioma compared to the AA+GA
      genotype (OR = 2.60, 95%CI = 1.08-6.28) in the regressive model. In conclusion,
      we report that the EFEMP1 rs3791679 polymorphism influences glioma susceptibility
      in the Chinese Han population.

PMID- 27706620
TI  - New chromosomal evidence for the origin of Triatoma infestans populations from
      Brazil.
AB  - In this study, the karyometry of different Triatoma infestans populations from
      different states of Brazil was analyzed and compared with those of a population
      from Cochabamba. No significant differences were found between the population
      from Cochabamba and those from Brazil. These results are consistent with the
      origin of the T. infestans populations of Brazil by a founder effect from
      Cochabamba. Moreover, these findings also confirm that a founder effect occurred
      during the dispersal of T. infestans populations in different Brazilian states.

PMID- 27706622
TI  - Investigation on ERCC5 genetic polymorphisms and the development of gastric
      cancer in a Chinese population.
AB  - Our study aimed to investigate the role of 2 ERCC5 promoter SNPs (rs2094258 and
      rs751402) in the development of gastric cancer in the Chinese population. The
      present hospital-based case-control study consisted of 155 patients with gastric
      cancer and 246 healthy controls recruited between March 2012 and December 2014.
      Genotyping for the rs2094258 and rs751402 polymorphic sites was carried out using
      polymerase chain reaction-restriction fragment length polymorphism. Statistical
      analyses were conducted using the SPASS version 16.0 software (SPSS, Inc.,
      Chicago, IL, USA). As determined by the chi-square test, there was a significant
      difference in the genotype distributions of rs751402 between patients and
      controls (X2 = 6.74, P = 0.03). By unconditional logistic regression analysis, we
      observed that the TT genotype in rs751402 was significantly associated with
      increased risk to gastric cancer as compared with the CC genotype, and the
      adjusted OR (95%CI) was 2.17 (1.15-4.09). Moreover, subjects carrying the T
      allele in rs751402 had elevated risk of developing gastric cancer when compared
      with those carrying the C allele, with an adjusted OR value (95%CI) of 1.47 (1.09
      1.99). In conclusion, we suggest that the ERCC5 rs751402 gene polymorphism may
      influence the susceptibility to gastric cancer in the Chinese population.

PMID- 27706621
TI  - Low levels of serum miR-99a is a predictor of poor prognosis in breast cancer.
AB  - MicroRNA (miRNA) deregulation has been previously linked to the initiation and
      development of breast cancer. Although miR-99a is aberrantly expressed in many
      types of cancers, including breast cancer, the serum miR-99a expression level in
      breast cancer and its clinical significance remains unknown. Blood samples were
      obtained from 72 patients with breast cancer and 40 healthy volunteers, and
      subjected to real-time polymerase chain reaction to evaluate the level of
      expression of serum miR-99a in the study participants. Furthermore, we
      investigated the association between serum miR-99a and the clinical outcome of
      breast cancer. Serum miR-99a expression was significantly downregulated in
      patients with breast cancer, compared to that in healthy controls (P < 0.01).
      Moreover, the serum miR-99a was correlated with various clinical parameters of
      breast cancer, including lymph node metastasis (P = 0.0194), distant metastasis
      (P = 0.0037), Ki67 intensity (P = 0.0164), TNM stage (P = 0.0096), and
      histological grade (P = 0.0051) of cancer. Additionally, breast cancer patients
      displaying lower miR-99a levels showed poorer overall survival rates (P =
      0.0411). The serum miR-99a level was also found to be an independent risk factor
      for breast cancer (hazard ratio = 3.176, 95% confidence interval = 1.543-7.360, P
      = 0.023). Our data indicated that serum miR-99a expression was downregulated in
      breast cancer patients; moreover, this downregulation was associated with poor
      prognosis, suggesting that serum miR-99a could function as a tumor suppressor in
      breast cancer.

PMID- 27706623
TI  - Development and significance of SCAR marker QG12-5 for Canarium album (Lour.)
      Raeusch by molecular cloning from improved RAPD amplification.
AB  - Sequence-characterized amplified region (SCAR) is a valuable molecular marker for
      the genetic identification of any species. This marker is mainly derived from
      molecular cloning of random amplified polymorphic DNA (RAPD). We have previously
      reported the use of an improved RAPD technique for the genetic characterization
      of different samples of Canarium album (Lour.) Raeusch (C. album). In this study,
      DNA fragments were amplified using improved RAPD amplified from different samples
      of C. album. The amplified DNA fragment was excised, purified from an agarose gel
      and cloned into a pGM-T vector; subsequently, a positive clone, called QG12-5 was
      identified by PCR amplification and enzymatic digestion and sequenced by Sanger
      di-deoxy sequencing method. This clone was revealed consisting of 510 nucleotides
      of C. album. The SCAR marker QG12-5 was developed using specifically designed PCR
      primers and optimized PCR conditions. This SCAR marker expressed seven continuous
      "TATG" [(TATG)n] tandem repeats, which was found to characterize C. album.
      Subsequently, this novel SCAR marker was deposited in GenBank with accession No.
      KT359568. Therefore, we successfully developed a C. album-specific SCAR marker
      for the identification and authentication of different C. album species in this
      study.

PMID- 27706624
TI  - Association of CYP1A1 (cytochrome P450) MspI polymorphism in women with
      endometriosis.
AB  - Endometriosis is a disease that affects 10 to 15% of the women of reproductive
      age. It is characterized by the presence of endometrial-like tissues outside of
      the uterus. Some definitions claim that the functional ectopic tissue is
      sensitive to the action of hormones. Severity of endometriosis is defined
      according to a system proposed by the American Society for Reproductive Medicine,
      which is based on laparoscopic findings. A large number of genetic polymorphisms
      has been reported for CYP1A1, the gene that is responsible for enzymes involved
      in stage I detoxification of xenobiotics; this gene is located at 15q22-24, and
      encodes an isoenzyme that catalyzes the oxidation of polycyclic aromatic
      hydrocarbons present in phenolic compounds and epoxides. The aim of this study
      was to analyze the frequency of the MspI polymorphism and its relation to
      endometriosis. We obtained peripheral blood samples from 52 women with
      endometriosis (confirmed by laparoscopy) as well as 42 women without
      endometriosis (control group). In the case group, the women were between 25 and
      35 years of age; the age range was between 25 and 57 years old in the control
      group. Molecular analysis was performed by polymerase chain reaction. We found a
      significant association (P = 0.039) between the polymorphic allele m1 and
      endometriosis (32.70%). In conclusion, this study showed that the m1 polymorphism
      is associated with endometriosis, and that W1/m1 and m1/m1 polymorphisms are more
      frequently observed in patients with infertility and severe endometriosis.

PMID- 27706625
TI  - Influence of interleukin-18 gene polymorphisms on acute pancreatitis
      susceptibility in a Chinese population.
AB  - We investigate the relationship between IL-18 -607C/A and -137G/C genetic
      polymorphisms and development of acute pancreatitis in a Chinese population. A
      total of 153 patients were consecutively recruited from the First Affiliated
      Hospital of Chongqing Medical University between January 2013 and November 2014.
      Genotyping of IL-18 -607C/A and -137G/C variants was performed using the
      polymerase chain reaction-restriction fragment length polymorphism method. We
      observed a significant difference between acute pancreatitis patients and control
      subjects with respect to age (t = 2.15, P = 0.02), gender (chi-square = 3.95, P =
      0.04), body mass index (t = 5.85, P < 0.001), and alcohol consumption (chi-square
      = 9.74, P = 0.002). Using chi-square tests, we found that the genotype
      distributions of IL-18 -607C/A (chi-square = 0.81, P = 0.67) and -137G/C (chi
      square = 1.16, P = 0.56) polymorphisms did not differ between the acute
      pancreatitis and control groups. Genotype frequencies of these variants were
      consistent with Hardy-Weinberg equilibrium in both patient and control groups. In
      addition, logistic regression analysis failed to identify a significant
      association between these polymorphisms and acute pancreatitis risk. Our study
      firstly examined their association in a Chinese population, and we suggest that
      the IL-18 -607C/A and -137G/ C polymorphisms do not influence susceptibility to
      acute pancreatitis in the Chinese population studied in the present study.

PMID- 27706626
TI  - Growth hormone polymorphisms and growth traits in Chinese Tibetan sheep Ovis
      aries.
AB  - Growth hormone (GH) plays an important role in promoting growth, protein and
      muscle accretion, and fat catabolism, suggesting that GH is a potential candidate
      gene affecting growth traits in vertebrates. In this paper, polymorphisms in GH
      were investigated in 632 Chinese Tibetan sheep, by using DNA sequencing. Three
      single nucleotide polymorphisms were identified, including two mutations
      (g.616G>A and g.624G>A) in intron 2 and one synonymous mutation (g.498G>C) in
      exon 2. Association analyses showed that both g.498G>C and g.616G>A were
      significantly associated with several growth traits (at P < 0.01 or P < 0.05) in
      three investigated breeds. Our results demonstrate that GH variation may be used
      as a molecular marker for growth traits in Chinese Tibetan sheep.

PMID- 27706627
TI  - Development of polymorphic microsatellite loci in Odontobutis obscura using
      Illumina paired-end sequencing and the test of cross-species amplification.
AB  - Odontobutis obscura is a bottom-dwelling freshwater fish native to East Asia. Its
      range encompasses southwest China, western Japan, and Geoje Island in South
      Korea. Despite its widespread range in China and Japan, only a small and
      spatially isolated population is found in South Korea. We developed a total of 23
      novel and polymorphic microsatellite loci of O. obscura using Illumina paired-end
      shotgun sequencing and characterized them using 80 Japanese and Korean samples.
      An extensive genetic polymorphism was detected at these 23 loci, with the
      observed number of alleles at a locus ranging from 2 to 15 and expected and
      observed heterozygosities ranging from 0 to 0.656 and 0 to 0.547, respectively.
      Korean O. obscura exhibited a much lower level of genetic variability than the
      Japanese population did, probably as a result of long-term isolation combined
      with historical bottlenecks. The Japanese and Korean populations showed a high
      level of genetic differentiation with FST = 0.700 and RST = 0.913. Many of our
      primer sets were successfully transferable to congeneric O. interrupta and O.
      platycephala, which exhibited even greater polymorphism than Korean O. obscura.
      In conclusion, our study showed that these 23 microsatellite markers are useful
      for understanding the conservation biology and population genetic structure of O.
      obscura and other congeneric species.

PMID- 27706628
TI  - Association between TNF-alpha rs1800629 polymorphism and the risk of myocardial
      infarction: A meta-analysis.
AB  - The tumor necrosis factor-alpha (TNF-alpha) G-308A polymorphism has been
      suggested to be a susceptibility factor for myocardial infarction (MI). However,
      differing results from various studies have led to controversial conclusions.
      Hence, we performed a meta-analysis to evaluate the association between TNF-alpha
      G-308A polymorphism and MI. Reported studies published before March 30, 2015 were
      included and analyzed from the PubMed and Embase databases. Study selection and
      data extraction were carried out independently by two authors. The odds ratios
      (ORs) and 95% confidence intervals (CIs) were used to evaluate the association
      between the selected variables using the Comprehensive Meta-Analysis v2.2
      software. In total, 12 publications with 13 case-control studies consisting of
      6037 cases and 7262 controls were included in our meta-analysis. The overall
      results showed that there was no significant association between TNF-alpha G-308A
      polymorphism and MI risk [A vs G: OR = 1.18, 95%CI = 0.94-1.48; AA vs GG: OR =
      1.23, 95%CI = 0.74-2.05; GA vs GG: OR = 1.22, 95%CI = 0.98-1.51; (GA+AA) vs G: OR
      = 1.21, 95%CI = 0.96-1.54; AA vs (GG+GA): OR = 1.16, 95%CI = 0.72-1.88]. However,
      when subgroup analysis was performed according to the stages of MI, results
      indicated that there was a significant association between TNF-alpha G-308A
      polymorphism and the risk of acute MI. Other subgroup analyses revealed no
      significant associations. Current evidence suggests that TNF-alpha G-308A
      polymorphism may be associated with increased risk for acute MI.

PMID- 27706629
TI  - Trans-translation ensures timely initiation of DNA replication and DnaA synthesis
      in Escherichia coli.
AB  - The trans-translation pathway, mediated by the transfer messenger RNA (tmRNA;
      encoded by the ssrA gene) and the SmpB protein (tmRNA-binding protein expressed
      in Salmonella enterica), which is conserved in bacteria, is required for various
      cellular processes. A previous study has shown that trans-translation is required
      to ensure timely (non-delayed) dnaA transcription and consequent initiation of
      DNA replication in Caulobacter crescentus. In this study, we observed that
      initiation of chromosome replication was delayed in Escherichia coli lacking the
      smpB and/or ssrA genes (DssrA, DsmpB, or DsmpBDssrA mutants). We observed that
      the growth rate of the mutant cells was much slower than that of its wild-type
      counterpart. However, the delayed initiation of replication and slower growth in
      the DssrA or DsmpB mutants were reversed by ectopic expression of tmRNA or SmpB.
      A synchronized DsmpBDssrA cell culture containing the dnaC2 mutant allele showed
      delayed protein (total and DnaA) accumulation per cell; DnaA accumulation was
      also delayed in the DsmpB. These results indicated that absence of trans
      translation leads to a delay in initiation of DNA replication, synthesis of total
      protein (including DnaA), and a decrease in E. coli growth rate. In summary, we
      propose that the trans-translation pathway is required to ensure timely
      initiation of replication, protein synthesis, and subsequent cell cycle
      progression.

PMID- 27706630
TI  - Simulating the selfing and migration of Luehea divaricata populations in the
      Pampa biome to investigate the conservation potential of their genetic resources.
AB  - Computer simulations are an important tool for developing conservation strategies
      for forest species. This study used simulations to investigate the genetic,
      ecological, and reproductive patterns that contribute to the genetic structure of
      the tree Luehea divaricata Mart. & Zucc. in five forest fragments in the
      Brazilian Pampa biome. Using the EASYPOP model, we determined the selfing and
      migration rates that would match the corresponding genetic structure of
      microsatellite marker data (based on observed and expected heterozygosity
      parameters). The simulated reproductive mode was mixed, with a high rate of
      outcrossing (rate = 0.7). This was consistent with a selfing-incompatible system
      in this species, which reduced, but did not prevent, selfing. The simulated
      migration rate was 0.02, which implied that the forest fragments were isolated by
      distance, and that the inbreeding coefficients were high. Based on Nei's gene
      diversity analysis, 94% of the genetic variability was distributed within the
      forest fragments, and only 6% of the genetic diversity was caused by differences
      between them. Furthermore, the minimum viable population and minimum viable area
      genetic conservation parameters (which determine conservation potential in the
      short and long term) suggested that only the Inhatinhum forest fragment had the
      short-term potential to maintain its genetic diversity. However, in the long
      term, none of the forest fragments proved to be sustainable, indicating that the
      populations will require intervention to prevent a decline in genetic
      variability. The creation of ecological corridors could be a useful solution to
      connect forest fragments and enhance gene flow between them.

PMID- 27706631
TI  - Effect of UBE3C polymorphisms on intramuscular fat content and fatty acid
      composition in Duroc pigs.
AB  - Ubiquitin protein ligase E3C (UBE3C) is involved in the ubiquitin-proteasome
      pathway, and several ubiquitin protein ligases are important for fat deposition
      and lipid metabolism. The objective of this study was to analyze the association
      between a single nucleotide polymorphism (SNP) of the UBE3C gene with
      intramuscular fat (IMF) content and fatty acid (FA) composition in Duroc pigs.
      Four SNP markers (g.1586399A>G, g.1591358G>A, g.1600132G>C, and g.1600166G>A) of
      porcine UBE3C were genotyped using the polymerase chain reaction-restriction
      fragment length polymorphism method, and their associations with IMF content and
      FA composition were investigated in a commercial Duroc pig population. Two SNP
      markers (g.1586399A>G and g.1591358G>A) were segregated among the pigs. No UBE3C
      polymorphisms at g.1600132G>C or g.1600166G>A were observed. The UBE3C
      g.1586399A>G SNP was significantly associated with IMF content, while the UBE3C
      g.1591358G>A SNP was associated with palmitic, stearic, eicosenoic, and
      eicosadienoic acid levels, and saturated FA levels. These results suggest that
      polymorphisms in porcine UBE3C are correlated with IMF content and FA
      composition, and confirm the importance of porcine UBE3C as a candidate gene for
      fat deposition in pigs.

PMID- 27706632
TI  - High levels of glucose promote the activation of hepatic stellate cells via the
      p38-mitogen-activated protein kinase signal pathway.
AB  - The relationship between the p38-mitogen-activated protein kinase (p38-MAPK)
      signal pathway and high glucose-induced hepatic stellate cell (HSC) activation
      was investigated in this study. Sixty human HSC samples were randomly selected
      and used in the control (cultured normally), high-glucose (cultured in the
      presence of high glucose), and blocking (cultured under high-glucose conditions
      in the presence of the p38-MAPK inhibitor, SB203580) groups. The cells were
      incubated for 120 h and subsequently analyzed for morphological changes by
      inverted microscopy and for a-smooth muscle actin (a-SMA) expression (to
      determine the degree of HSC activation) by the method of streptavidin-biotin
      complex and western blot. Phospho-p38-MAPK protein expression was analyzed by
      western blotting. a-SMA and phospho-p38-MAPK expression was significantly
      upregulated in HSCs cultured under high-glucose conditions, compared to the HSCs
      cultured normally (P < 0.01). On the other hand, phospho-p38-MAPK and a-SMA
      protein levels were significantly lower in the blocking group compared to the
      high-glucose group (P < 0.01). Based on these results, we concluded that high
      glucose levels induce HSC activation mediated by phospho-p38-MAPK. Therefore,
      blocking the p38-MAPK signal pathway could inhibit this effect.

PMID- 27706633
TI  - Correlative study between the JAK2V617F mutation and thrombosis in patients with
      myeloproliferative neoplasm.
AB  - In this study, we investigated the correlation between the JAK2V617F mutation and
      thrombosis in patients with myeloproliferative neoplasm (MPN) using real-time
      fluorescence quantitative PCR. The incidence of thrombus was monitored and blood
      and coagulation were routinely assayed in patients with MPN. The JAK2V617F
      mutation was found in 8/68 individuals in the control group (11.8%); it was
      expressed in 44/68 patients with MPN (64.7%), suggesting that the rate of this
      mutation was significantly higher in patients with MPN than that in the control
      group. Twenty-six MPN patients (38.2%) showed symptoms of thrombosis; MPN
      patients with thrombosis showed a significantly higher rate of the JAK2V617F
      mutation, were of a greater age, and had higher blood pressure than MPN patients
      without thrombosis. In addition, the white blood cells (WBC) (21.98 +/- 1.95) and
      platelets (364.68 +/- 97.72) were significantly higher in patients, expressing
      the mutated gene, with polycythemia vera than in the patients without the
      mutation. The WBC (32.89 +/- 4.25) and hemoglobin (161.92 +/- 16.19) were
      significantly increased in the essential thrombocythemia patients with gene
      mutation compared with the patients without mutation. MPN patients showed higher
      blood clotting ability than the control subjects; moreover, MPN patients with the
      JAK2V617F mutation showed higher blood clotting ability than those without the
      mutation. The findings of this study indicate that the JAK2V617F mutation is
      correlated with the incidence of thrombosis, and analysis of this mutation has
      important clinical significance in the diagnosis and treatment of MPN.

PMID- 27706634
TI  - Kallikrein 12 downregulation reduces AGS gastric cancer cell proliferation and
      migration.
AB  - Abnormal expression of the kallikrein (KLK) family of serine proteases closely
      correlates with onset, progression, and prognosis of endocrine gland-related
      malignant tumors. The aim of this study was to evaluate how downregulation of
      KLK12 influenced cell cycle and proliferation of the AGS gastric cancer cell
      line. KLK12 was detected by western blot in GES-1 normal gastric epithelial and
      AGS cells. AGS cells were transfected with KLK12 siRNA, a negative control siRNA,
      or subjected to a mock transfection, following which, we assessed mRNA and
      protein levels, cell proliferation, cell migration, and cell cycle progression.
      We found that KLK12 levels were significantly higher in AGS cells than in GES-1
      cells. Transfection of AGS cells with KLK12 siRNA led to downregulation of KLK12
      mRNA and protein expression, reduced cell proliferation (0.47 +/- 0.03 vs 0.92 +/
      0.04, P < 0.01), and lower cell counts (3.92 +/- 0.25 x 105 vs 5.47 +/- 0.50 x
      105, P < 0.01) with respect to the negative control. We observed that KLK12 siRNA
      increased the number of AGS cells in G0/G1 and reduced those in S phase.
      Furthermore, downregulation of KLK12 in AGS cells decreased their ability to
      penetrate the membrane in a migration assay (P < 0.05). In conclusion, KLK12
      siRNA inhibited the proliferation and migration of AGS gastric cancer cells and
      caused their arrest in the G0/G1 phase of the cell cycle.

PMID- 27706635
TI  - miR-146a and miR-196a2 polymorphisms in ovarian cancer risk.
AB  - We investigated the relationship between miR-146a and miR-196a2 genetic
      polymorphisms and development of ovarian cancer in a Chinese population. A total
      of 134 patients and 227 control subjects were involved in our study between
      January 2012 and October 2014 from China-Japan Union Hospital of Jilin
      University. Genotyping of miR-146a and miR-196a2 was accomplished by polymerase
      chain reaction coupled with restriction fragment length polymorphism analysis.
      Unconditional multiple-logistic regression analysis indicated that the GG
      genotype of miR-146a was associated with an increased risk of ovarian cancer when
      compared to the CC genotype, and the adjusted OR (95%CI) was 3.73 (1.79-7.80).
      Moreover, the CG+GG genotype of miR-146a was associated with an increased risk of
      ovarian cancer compared with the CC genotype (OR = 1.68, 95%CI = 1.06-2.66), and
      the GG genotype had a higher risk of ovarian cancer than the CC+CG genotype (OR =
      3.02, 95%CI = 1.55-5.98). In conclusion, our study suggests that the miR-146a
      polymorphism is associated with increased risk of ovarian cancer and could be
      used as a biomarker for ovarian cancer susceptibility.

PMID- 27706636
TI  - DNA barcoding reveals high levels of genetic diversity in the fishes of the
      Itapecuru Basin in Maranhao, Brazil.
AB  - DNA barcoding is a useful complementary tool for use in traditional taxonomic
      studies due to its ability to detect cryptic species, and may be particularly
      efficient in the identification of fish species. The fish fauna of the Itapecuru
      River represents an important fishery resource in the Brazilian State of
      Maranhao, although it is currently suffering increasing degradation as a result
      of anthropogenic impacts. Therefore, DNA barcoding was used in the present study
      to identify fish species and establish a database of the rich freshwater fish
      fauna of Maranhao. A total of 440 specimens were analyzed, corresponding to 64
      species belonging to 59 genera, 31 families, and 10 orders. Overall, 92.19% of
      these species could be identified by DNA barcoding, and were characterized by low
      levels (average 0.80%) of intra-specific divergence. However, five species
      (Anableps anableps, Gymnotus carapo, Sciades couma, Pseudauchenipterus nodosus,
      and Leporinus piau) presented values of mean genetic divergence above 3%,
      indicating the existence of cryptic diversity in these fishes. The DNA barcoding
      approach permitted the analysis of a large number of specimens and facilitated
      the discrimination and identification of closely related fish species in the
      Itapecuru Basin.

PMID- 27706637
TI  - MicroRNA variants and colorectal cancer risk: a meta-analysis.
AB  - Colorectal cancer (CRC) is a multi-factorial disease, and genetic background may
      contribute to its etiology. Single nucleotide polymorphisms (SNPs) in microRNAs
      (miRNAs) may be used as specific markers of predisposition for CRC diagnosis and
      prevention. In this review, we summarize and discuss recent publications
      evaluating the roles of miRNA SNPs in CRC. A meta-analysis was also carried out
      to assess the association between the five most frequently studied miRNA SNPs and
      CRC risk. No relationship was established between this disease and the three SNPs
      rs11614913, rs2910164, and rs3746444 in miR-196a-2, miR-146a, and miR-499,
      respectively. However, polymorphisms of miR-149 (rs2292832; CT vs TT: odds ratio
      [OR] = 0.816, 95% confidence interval [CI] = 0.691-0.963; CC+CT vs TT: OR =
      0.834, 95%CI = 0.715-0.972) and pre-miR-27a (rs895819; GG vs AA: OR = 1.534,
      95%CI = 1.148-2.049; GG+AG vs AA: OR = 1.324, 95%CI = 1.066-1.645) were found to
      be associated with CRC in our analysis. In conclusion, the SNPs rs2292832 in miR
      149 and rs895819 in pre-miR-27a were associated with CRC susceptibility, whereas
      rs11614913, rs2910164, and rs3746444 in miR-196a-2, miR-146a, and miR-499,
      respectively, were not. Further studies should be carried out to validate these
      findings.

PMID- 27706638
TI  - Population genetic structure and its implication in the conservation of
      Schizopygopsis pylzovi in Yellow River as inferred from mitochondrial DNA
      sequence analysis.
AB  - To assess the genetic diversity, structure, and population dynamics of
      Schizopygopsis pylzovi, we examined the changes in mitochondrial DNA sequences
      (the mtDNA control region and the Cyt b gene; 1835 bp) in 304 individuals from
      nine populations. The samples were segregated into 112 haplotypes, with high
      haplotype diversity and low nucleotide diversity. The haplotype diversity was
      highest in the Minhe (HS) range of Huangshui River and lowest in the Weiyuan (WY)
      range of Weihe River. Analysis of molecular variance showed that 69.64% of the
      total genetic variance was contributed by within-the-group variation and 30.36%
      was contributed by among-the-group variation. Pairwise FST revealed significant
      divergence between the populations. The FST between the MT and WY was highest,
      and that between the YZ and YJ was lowest. The neighbor-joining phylogenetic tree
      demonstrated that all geographic populations were not monophyletic, but
      overlapped each other, indicating that the duration of geographical isolation was
      not long enough or the populations had not yet reached significant genetic
      isolation or differentiation at the monophyletic level. Tajima's D and Fu's Fs
      were negative and statistically significant, indicating that S. pylzovi had
      experienced certain population expansion events, which is consistent with the
      hypothesis that the headwater area of the Yellow River was dramatically affected
      by the geological and climatic upheaval during the Quaternary ice age. Our
      analysis indicated that the management units corresponding to the WY population
      should be managed and conserved first. In situ conservation is first recommended
      to protect the original habitat from further destruction.

PMID- 27706639
TI  - Molecular characterization and upregulation of cytosolic manganese superoxide
      dismutase by imidazole derivative KK-42 in Macrobrachium nipponense.
AB  - Imidazole derivative KK-42 is a well-known regulator of insect growth. KK-42
      pretreatment has been shown to promote the survival of Macrobrachium nipponense
      infected with Aeromonas hydrophila, possibly via activation of superoxide
      dismutase (SOD). In this study, the cytMnSOD gene was cloned from the
      hepatopancreas of M. nipponense using the rapid amplification of cDNA ends
      technique. The full-length cDNA of cytMnSOD was 1233 bp long, and the open
      reading frame was 858 bp long, encoding a 286-aa protein with a 60-aa leader
      sequence. The calculated molecular mass of the translated cytMnSOD protein was
      31.33 kDa, with an estimated isoelectric point of 5.62. cytMnSOD contained two N
      glycosylation sites, four conserved amino acids responsible for binding
      manganese, and a manganese SOD domain (DVWEHAYY). Real-time RT-PCR analysis
      showed that cytMnSOD was expressed in all tissues examined with the highest
      expression observed in the hepatopancreas. Levels of the cytMnSOD transcript in
      the hepatopancreas were highest in stage C of the molting cycle. Real-time PCR
      analysis revealed that cytMnSOD expression increased significantly 3, 6, and 12 h
      after KK-42 treatment, with simultaneous increases in SOD activity from 6 to 12
      h. Our results demonstrate that cytMnSOD expression and SOD activity may be
      induced by KK-42, which may represent one of the molecular mechanisms through
      which KK-42 promotes increased survival of prawns infected with A. hydrophila.

PMID- 27706640
TI  - Characterization and evolution of the mitochondrial DNA control region in Ranidae
      and their phylogenetic relationship.
AB  - The control region is considered to be one of the most variable parts of animal
      mitochondrial DNA (mtDNA). We compared the mtDNA control region from 37 species
      representing 14 genera and 4 subfamilies of Ranidae, to analyze the evolution of
      the control region and to determine their phylogenetic relationship. All the
      Ranidae species had a single control region, except four species that had two
      repeat regions. The control region spanned the region between the Cyt b and
      tRNAleu genes in most of the Ranidae species. The length of the control region
      sequences ranged from 1186 bp (Limnonectes bannaensis) to 6746 bp (Rana
      kunyuensis). The average genetic distances among the species varied from 1.94%
      (between R. chosenica and R. plancyi) to 113.25% (between Amolops ricketti and
      Euphlyctis hexadactylus). The alignment of three conserved sequence blocks was
      identified. However, conserved sequence boxes F to A were not found in Ranidae. A
      maximum likelihood method was used to reconstruct the phylogenetic relationship
      based on a general time reversible + gamma distribution model. The amount of A+T
      was higher than G+C across the whole control region. The phylogenetic tree
      grouped members of the respective subfamilies into separate clades, with the
      exception of Raninae. Our analysis supported that some genera, including Rana and
      Amolops, may be polyphyletic. Control region sequence is an effective molecular
      mark for Ranidae phylogenetic inference.

PMID- 27706641
TI  - Genetic diversity and population structure of Fenneropenaeus penicillatus
      determined by mitochondrial DNA analyses.
AB  - Fenneropenaeus penicillatus is a widely distributed economically and ecologically
      important shrimp species, which is endangered in China. Sequence analysis of 16s
      rRNA and control region (CR) fragments from mitochondrial DNA was conducted to
      obtain information on genetic diversity and population structure. Individuals
      from 12 wild F. penicillatus populations located along the southeast coast of
      China were used. Polymerase chain reaction (PCR) fragments of the CR gene
      revealed high genetic diversity among the 12 populations; however, PCR fragments
      of the 16s rRNA gene revealed very low genetic diversity in the Hainan (HN) and
      Ningde (ND) populations and high genetic diversity in the DS, BH, PT, XM, and SZ
      populations. Data obtained from the CR and 16s rRNA genes suggested that high
      genetic differentiation exists among the 12 populations, which is mainly due to
      the high genetic differentiation between HN and all other 11 populations. These
      results may be useful for further sustainable management and utilization of this
      species.

PMID- 27706642
TI  - Snail-induced epithelial-mesenchymal transition in gastric carcinoma cells and
      generation of cancer stem cell characteristics.
AB  - Biological changes in Snail-overexpressed SGC7901 cells were studied by
      establishing a pEGFP-C1-Snail carrier. The significance of Snail in epithelial
      mesenchymal transition (EMT) as well as the invasion and metastatic capacity of
      gastric cancer cells was also discussed; moreover, we attempted to verify the
      probable cancer stem cell characteristics of Snail-overexpressed cells. A pEGFP
      C1-Snail eukaryotic expression plasmid was constructed and pEGFP-C1(-) and pEGFP
      C1-Snail plasmids were extracted and transfected into SGC7901 cells using
      Lipofectamine 2000. Stably expressed SGC7901-N [control group containing pEGFP
      C1(-)] and SGC7901-S (test group containing pEGFP-C1-Snail) cells were screened
      using a G418 resistance medium. Snail, E-cadherin, b-catenin, vimentin, and
      fibronectin gene and protein expressions were detected by real-time quantitative
      PCR, western blot, and immunofluorescence. Cell invasion and metastasis were
      tested by scratch test, invasion assay, and an adhesion experiment. The positive
      rate of aldehyde dehydrogenase-1 (ALDH-1) expression was analyzed by flow
      cytometry. The results indicated the occurrence of EMT, accompanied by
      morphological changes in the cells and a weakening of the cell adhesion capacity.
      We also observed a decrease in the expression of epithelial markers E-cadherin
      and b-catenin and an increase in mesenchymal (Snail and vimentin) marker
      expression. Moreover, the cells showed increased invasiveness and metastatic
      capacity, and decreased proliferative ability. Moreover, the Snail-treated
      SGC7901 cells moved towards the scratch and produced fewer clones compared to the
      control cells. Owing to its capacity for self-renewal, SGC7901-S cells produced
      new clones and expressed ALDH-1. Therefore, we concluded that Snail
      overexpression induced EMT and endowed cells with tumor stem cell
      characteristics.

PMID- 27706643
TI  - Development of SNP-based dCAPS markers for identifying male sterile gene tms5 in
      two-line hybrid rice.
AB  - Molecular markers can increase both the efficiency and speed of breeding
      programs. Functional markers that detect the functional mutations causing
      phenotypic changes offer a precise method for genetic identification. In this
      study, we used newly derived cleaved amplified polymorphic sequence markers to
      detect the functional mutations of tms5, which is a male sterile gene that is
      widely used in rice production in China. In addition, restriction cutting sites
      were designed to specifically digest amplicons of tms5 but not wild type (TMS5),
      in order to avoid the risk of false positive results. By optimizing the condition
      of the polymerase chain reaction amplifications and restriction enzyme
      digestions, the newly designed markers could accurately distinguish between tms5
      and TMS5. These markers can be applied in marker-assisted selection for breeding
      novel thermo-sensitive genic male sterile (TGMS) lines, as well as to rapidly
      identify the TGMS hybrid seed purity.

PMID- 27706644
TI  - Detection of Jaagsiekte sheep retrovirus in the peripheral blood during the pre
      clinical period of ovine pulmonary adenomatosis.
AB  - The envelope protein (Env) of the Jaagsiekte sheep retrovirus (JSRV) is known to
      be a unique oncoprotein responsible for inducing ovine pulmonary adenocarcinoma
      (OPA). The objective of this study was to prepare a specific monoclonal antibody
      (mAb) against the JSRV Env protein using bioinformatic analysis. According to the
      structure and epitope prediction results of JSRV Env, the JSRV-Env572-615 antigen
      was prepared via peptide synthesis (amino acid sequence 572-615, denoted as JSRV
      Env572-615). BALB/c mice were immunized to prepare the anti-JSRV-Env572-615 mAb.
      Spleen cells were fused with SP2/0 myeloma cells after being screened by indirect
      ELISA and cloned by limiting dilution. The specificity of mAb was evaluated by
      western blot analysis and immunohistochemistry assays. Western blot results
      showed that the JSRV Env protein was able to bind to mAb with high specificity.
      Immunohistochemistry assays demonstrated that the mAb was able to recognize JSRV
      Env in adenomatous hyperplasia of the lung. Furthermore, JSRV was detected in
      peripheral blood leukocytes during the pre-clinical period of OPA in 2 of the 25
      sheep using this newly synthesized mAb. Therefore, this mAb may be a useful tool
      for the detection of JSRV in sheep.

PMID- 27706645
TI  - Twisting of the spermatic cord: ischemia and reperfusion, toxicogenetic
      evaluation, and the effects of phosphatidylcholine in pre-clinical trials.
AB  - Phosphatidylcholine is the main phospholipid present in cell membranes and in
      lipoproteins, and can interfere with various biological processes. This lipid
      also has antioxidant activity, and protects against damage caused by free
      radicals under conditions of ischemia/reperfusion. Therefore, the present study
      was designed to evaluate toxicogenetic damage caused by twisting of the spermatic
      cord in ischemia/reperfusion, and whether phosphatidylcholine plays a role in
      conditions of ischemia/reperfusion in preclinical trials. The results indicate
      that spermatic cord torsion does not cause genotoxic damage or mutagenesis. A
      dose of 300 mg/kg of phosphatidylcholine is toxic and is thus not recommended.
      However, a dose of 150 mg/kg does not promote toxicogenetic damage, and though it
      does not statistically prevent tissue damage occurring from lack of oxygenation
      and nutrition of testicular cells, it has a tendency to reduce this damage.
      Therefore, this research suggests that further studies should be conducted to
      clarify this tendency and to provide a better explanation of the possible
      therapeutic effects of phosphatidylcholine in cytoprotection of germ cells
      affected by ischemia/reperfusion.

PMID- 27706646
TI  - Immunological function and antibacterial activity of two ferritin proteins from
      the freshwater pearl mussel Hyriopsis schlegelii.
AB  - Ferritin is a conserved iron-binding protein involved in host defense and
      cellular iron metabolism in most organisms. We investigated the expression
      profiles of two ferritin genes (designated HsFer-1 and HsFer-2) in the hemocytes,
      gonad, and hepatopancreas of Hyriopsis schlegelii, when challenged with bacteria
      and metal ions. HsFer gene transcription increased 1.8-7.7- and 1.9-6.1-fold in
      these tissues after stimulation with Staphylococcus aureus and Vibrio
      anguillarum, respectively. In addition, following exposure to Fe3+, expression of
      HsFer-1 and HsFer-2 was elevated by 1.5-6.1- and 3.6-10.1-fold, respectively.
      Levels of HsFer-1 and -2 mRNA also increased significantly after treatment with
      Cu2+ and Pb2+ at certain concentrations. Moreover, recombinant HsFer-1 and -2
      were able to inhibit the growth of two strains of bacteria, and the former
      efficiently chelated Fe3+. From these results, we conclude that HsFer-1 and -2
      may be involved in iron metabolism and immune defense by inhibiting the growth of
      bacteria.

PMID- 27706647
TI  - Molecular cloning and expression pattern of oriental river prawn (Macrobrachium
      nipponense) nitric oxide synthase.
AB  - Nitric oxide synthase (NOS) produces nitric oxide (NO) by catalyzing the
      conversion of l-arginine to l-citrulline, with the concomitant oxidation of
      nicotinamide adenine dinucleotide phosphate. Recently, various studies have
      verified the importance of NOS invertebrates and invertebrates. However, the NOS
      gene family in the oriental river prawn Macrobrachium nipponense is poorly
      understood. In this study, we cloned the full-length NOS complementary DNA from
      M. nipponense (MnNOS) and characterized its expression pattern in different
      tissues and at different developmental stages. Real-time quantitative polymerase
      chain reaction (RT-qPCR) showed the MnNOS gene to be expressed in all
      investigated tissues, with the highest levels observed in the androgenic gland (P
      < 0.05). Our results revealed that the MnNOS gene may play a key role in M.
      nipponense male sexual differentiation. Moreover, RT-qPCR revealed that MnNOS
      mRNA expression was significantly increased in post-larvae 10 days after
      metamorphosis (P < 0.05). The expression of this gene in various tissues
      indicates that it may perform versatile biological functions in M. nipponense.

PMID- 27706648
TI  - Allele- and parent-of-origin-specific effects on expression of the KCNJ11 gene: A
      candidate for meat tenderness in cattle.
AB  - In contrast to the Mendelian inheritance model, parental alleles can contribute
      unequally to gene expression, which may result in phenotypic variance among
      individuals and bias in the predicted additive effect of molecular markers
      associated with production traits. Given the need to understand the effects of
      allelic variation and parent-of-origin effects on the expression of genes with a
      commercial interest in cattle, we analyzed the expression of KCNJ11 (potassium
      inwardly rectifying channel, subfamily J, member 11), which was previously
      described as a functional candidate gene for meat tenderness. Allele-specific and
      parent-of-origin-dependent expression of this gene were assessed in bovine muscle
      using the rs379610823 single nucleotide polymorphism as a reference. Biallelic
      expression was observed; however, the T allele was expressed at significantly
      higher levels than the C allele. Furthermore, increased expression of KCNJ11 was
      found in animals harboring the maternal T allele. This study is the first to
      describe the differential allelic expression of bovine KCNJ11. Our findings are
      important for understanding the mechanisms that underlie the pattern of KCNJ11
      expression and its potential impact on the phenotypic variation of meat
      tenderness in Nelore beef cattle. This reinforces the need for further
      investigation of allelic- and parent-of-origin expression deviation in genetic
      markers eligible for the selection of target traits.

PMID- 27706649
TI  - Effect of 1,25-(OH)2D3 and lipopolysaccharide on mononuclear cell inflammation in
      type 2 diabetes mellitus and diabetic nephropathy uremia.
AB  - The prevention and treatment of type-2 diabetes mellitus (T2DM) and diabetic
      nephropathy (DN), which are disorders with high incidence rates, is of primary
      importance. In this study, we analyzed the effect of 1,25-(OH)2D3 and
      lipopolysaccharide (LPS) in combination with interleukin (IL)-15 on the
      inflammatory immune response and expression of vitamin D receptor (VDR) in
      mononuclear cells of T2DM and DN uremia (DNU) patients. The human acute monocytic
      leukemia cell line THP-1 was treated with peripheral blood serum isolated from 30
      healthy controls and T2DM and DNU patients each, cultured in the presence or
      absence of 1,25-(OH)2D3, and subsequently treated with LPS and IL-15. The VDR
      mRNA and protein expression in THP-1 cells was detected by real-time polymerase
      chain reaction and western blot (and immunofluorescence assay), respectively, and
      IL-6 and IL-10 concentrations in the culture supernatant were detected by enzyme
      linked immunosorbent assay. LPS treatment induced a significant decrease in VDR
      mRNA expression in T2DM and DNU serum-treated THP-1 cells compared to the control
      cells (P < 0.05). The VDR protein expression in DNU serum-treated THP-1 cells was
      also significantly down-regulated (P < 0.05). LPS treatment induced IL-6
      secretion in serum-treated THP-1 cells (P < 0.05), while 1,25-(OH)2D3 treatment
      inhibited IL-6 secretion to some extent. These findings suggested that LPS down
      regulates the expression of VDR in mononuclear cells of T2DM and DNU patients and
      induces an imbalance in the pro-inflammatory and anti-inflammatory cytokine
      response, while 1,25-(OH)2D3 partially reversed the effect of LPS and protected
      patients with T2DM and DNU.

PMID- 27706650
TI  - Association between -1082G/A, -819C/T, and -592C/A genetic polymorphisms in IL-10
      and risk of type 2 diabetes mellitus in a Chinese population.
AB  - Type 2 diabetes mellitus is the most common form of endocrine disease in humans;
      genetic factors are known to contribute to the development of this disease. In
      this case-control study, we investigated the relationship between the -1082G/A, 
      819C/T, and -592C/A polymorphisms in interleukin 10 (IL-10) and the pathogenesis
      of type 2 diabetes mellitus in a Chinese population. Patients with type 2
      diabetes mellitus (N = 228) and control subjects (N = 240) were recruited from
      the Department of Endocrinology at the People's Hospital of Linyi City, between
      September 2013 and April 2015. The IL-10 -1082G/A, -819C/T, and -592C/A
      polymorphisms were genotyped by polymerase chain reaction-restriction fragment
      length polymorphism. Multivariate logistic regression analyses revealed that
      patients carrying the AA genotype of IL-10 -592C/A were at a higher risk of
      developing type 2 diabetes mellitus compared to those carrying the CC genotype
      [adjusted odds ratio (OR) = 1.74; 95% confidence interval (CI) = 1.03-2.95]. In
      addition, individuals carrying the A allele of IL-10 -592C/A showed a 1.34-fold
      higher risk of developing type 2 diabetes mellitus compared to those carrying the
      C allele (adjusted OR = 1.34; 95%CI = 1.03- 1.75). There was no significant
      correlation between the IL-10 -1082G/ A and -819C/T polymorphisms and risk of
      type 2 diabetes mellitus. In conclusion, this study shows that the -1082G/A
      polymorphism of IL-10 contributes to the onset of type 2 diabetes mellitus, and
      may be considered a biomarker for early screening of type 2 diabetes mellitus in
      the Chinese population studied here.

PMID- 27706651
TI  - Promoter methylation and histone modifications affect the expression of the
      exogenous DsRed gene in transgenic goats.
AB  - Transgene silencing, which is common in transgenic plants and animals, limits the
      generation and application of genetically modified organisms, and is associated
      with the exogenous gene copy number, the methylation status of its promoters, and
      histone modification abnormalities. Here, we analyzed the expression of the
      exogenous gene DsRed and the methylation status of its cytomegalovirus (CMV)
      promoter in six healthy transgenic cashmere goats and transgenic nuclear donor
      cells. The CMV promoter exhibited high methylation levels (74.4-88.2%) in four of
      the goats, a moderate methylation level (58.7%) in one, and a low methylation
      level (21.2%) in one, while the methylation level of the transgenic nuclear donor
      cells was comparatively low (14.3%). DsRed expression was negatively correlated
      with promoter methylation status. Transgenic cashmere goats carried one to three
      copies of the CMV promoter fragment and one to six copies of the DsRed fragment,
      but copy number showed no obvious correlation with DsRed expression. After
      treatment with the methylation inhibitor 5-azacytidine, DsRed expression in
      transgenic goat cells significantly increased and CMV promoter methylation
      significantly decreased; this indicated an inverse correlation between promoter
      methylation status and DsRed expression. After treatment with the histone
      deacetylase inhibitor trichostatin A, DsRed expression increased, indicating that
      an abnormal histone modification in transgenic goats is also involved in
      exogenous gene silencing. These findings indicate the potential of trichostatin A
      and 5-azacytidine to rescue the biological activity of silenced exogenous
      transgenes in adult-derived transgenic cells under culture conditions.

PMID- 27706652
TI  - Identification of low potassium stress-responsive proteins in tobacco (Nicotiana
      tabacum) seedling roots using an iTRAQ-based analysis.
AB  - Potassium is one of the three main mineral nutrients, and is vital for leaf
      growth and the quality of tobacco (Nicotiana tabacum) plants. In recent years,
      the isobaric tags for relative and absolute quantitation (iTRAQ) method has been
      one of the most popular techniques for quantitative proteomic analysis. In this
      study, we used iTRAQ to compare protein abundances in the roots of control and
      low potassium-treated tobacco seedlings, and found that 108 proteins were
      differentially expressed between the two treatments. Of these, 34 were
      upregulated and 74 were downregulated, and 39 (36%) were in the chloroplasts.
      Kyoto Encyclopedia of Genes and Genomes pathway enrichment results suggested that
      metabolic pathways were the dominant pathways (10 upregulated and 14
      downregulated proteins). Ten proteins involved in the pyruvate metabolism pathway
      increased their expression levels, and 17 upregulated proteins were enriched in
      the ribosomes category. To evaluate correlations between protein and gene
      transcript abundances, the expression patterns of 12 randomly chosen genes were
      examined. A quantitative real-time polymerase chain reaction revealed that the 12
      genes were induced after low potassium treatment for 3, 6, 12, and 24 h. Our
      results demonstrate that low potassium levels affect protein profiles in tobacco
      roots.

PMID- 27706653
TI  - Diallel analysis to choose parents for black bean (Phaseolus vulgaris L.)
      breeding.
AB  - In this study, conducted in two different seasons, we aimed to choose parents to
      obtain promising segregating populations for the extraction of black bean
      (Phaseolus vulgaris L.) lines that are superior in terms of disease resistance,
      plant architecture, and grain yield. Twelve parents were arranged in two groups
      to compose a partial diallel in a 5 x 7 scheme. Group 1 was composed of parents
      with black grains and erect plant architecture, while group 2 was composed of
      parents that had carioca grains and were resistant to the main fungal diseases
      that occur in the common bean. The following traits were evaluated: severity of
      angular leaf spot (ALS), plant architecture (PAG), and grain yield (YIELD). The
      data were analyzed according to a partial diallel model using parents and F1
      hybrids. In the genetic control of ALS and PAG, additive effects were
      predominant, while for YIELD, additive effects were predominant in one season and
      dominance effects were in another season, because it is a more complex trait than
      ALS and PAG. For YIELD, we observed an interaction between general combining
      ability and specific combining ability between seasons. The genes that control
      ALS, PAG, and YIELD were in eight of the 12 parents evaluated in the diallel. The
      cultivar 'BRS Estilo' is suitable to use as a parent in common bean breeding in
      terms of ALS, PAG and YIELD. Recurrent selection is the most recommended option
      for simultaneously breeding for PAG, YIELD, and resistance to angular leaf spot
      in bean culture.

PMID- 27706655
TI  - Transcriptome analysis of potential simple sequence repeat markers in
      Ammopiptanthus mongolicus.
AB  - Ammopiptanthus mongolicus, an evergreen broadleaf legume shrub, can survive under
      conditions of high and low temperature, extreme salinity, and drought. This
      attribute makes it an ideal model for studying mechanisms of stress tolerance in
      plants. However, simple sequence repeat (SSR) resources for this species are
      insufficient in public databases. In this study, a total of 44,959 unigenes
      identified from the A. mongolicus transcriptome were used for SSR analysis by
      MIcroSAtellite (MISA). A total of 13,859 SSRs were found to be distributed within
      10,409 unigenes, with an average length of 15 bp and an average density of one
      SSR per 4.4 kb. There were 222 different motif types in the A. mongolicus
      transcriptome, and mononucleotide repeats represented the main type, accounting
      for 44.2% of all SSRs. The (A/T)n repeat was the most frequent motif, accounting
      for 42.37% of all SSRs. We also performed Gene Ontology functional analysis,
      Kyoto Encyclopedia of Genes and Genomes database pathway analysis, and eggNOG
      analysis, and identified 6157, 2301, and 9845 unigenes containing SSRs in these
      three databases, respectively. The functional categorization of A. mongolicus
      unigenes containing SSRs revealed that these unigenes represent many transcribed
      genes with different functions. These data provide sequence information that may
      be used to improve molecular-assisted markers for the study A. mongolicus genetic
      diversity.

PMID- 27706654
TI  - Characterization of the complete mitochondrial genome and phylogenetic
      relationships of the three-spot swimming crab (Portunus sanguinolentus).
AB  - In this study, we determined the whole mitochondrial genome profile of the three
      spot swimming crab (Portunus sanguinolentus) and elucidated phylogenetic
      relationships between representative species in the order Decapoda. The
      mitochondrial genome was 16,024 bp in length and consisted of 13 protein-coding
      genes, 22 transfer RNA genes, two ribosomal RNA genes, and a putative control
      region. Of the 37 genes, 23 were encoded by the heavy strand while 14 were
      encoded by the light strand. Four types of start codons were identified; ATG
      initiated nine genes, ATT initiated two genes, and ATC and GTG each started one
      gene. Nine protein-coding genes ended with a complete TAA or TAG stop codon, and
      four genes ended with an incomplete T or TA codon. Fourteen non-coding regions
      were found, which ranged from 1 to 34 bp in length. Nine overlaps were observed,
      with lengths between 1 and 7 bp. Phylogenetic analysis suggested that P.
      sanguinolentus is genetically closest to P. trituberculatus and P. pelagicus.
      Charybdis feriata, C. japonica, and Thalamita crenata formed a single cluster,
      and were close to the genera Callinectes and Portunus. Therefore, the genera
      Charybdis and Thalamita should be classified into the subfamily Portuninae.

PMID- 27706656
TI  - Evaluation of serum HGF and CK18 levels in patients with esophageal cancer.
AB  - Cytokeratins are thought to play a role in apoptosis. Cytokeratin 18 (CK18) is
      involved in the formation of intracellular cytoskeleton, and has been considered
      a promising apoptosis marker in gastrointestinal carcinomas. Growth factors,
      including hepatocyte growth factor (HGF), may provide a microenvironment for
      malignant cells. In this study, we aimed to compare serum HGF and CK18 levels
      between esophageal squamous cell carcinoma patients and healthy controls. The
      study included 41 adult patients (20 male, 21 female) diagnosed with esophageal
      squamous cell carcinoma, with a mean age of 63.54 +/- 10.88 years (range, 41-82
      years). We also recruited 39 age and gender-matched healthy control subjects.
      Venous blood samples were taken; serum HGF and CK18 concentrations were
      determined via ELISA. Results indicated that serum HGF levels were higher in
      patients (1.37 +/- 0.63 ng/mL) as compared to the healthy subjects (0.41 +/- 0.29
      ng/mL). Similarly, serum CK18 levels were higher in the patient group (2.53 +/-
      1.33 ng/mL) than in the control group (0.34 +/- 0.23 ng/mL) (P < 0.001). In
      addition, serum HGF and CK18 levels were positively correlated with metastasis
      stage, tumor stage, and disease stage of esophageal squamous cell carcinoma. To
      our knowledge, this is the first study to evaluate serum HGF and CK18 levels in
      patients with esophageal squamous cell carcinoma. The results suggest that serum
      CK18 and HGF levels may be used as prognostic and disease monitoring biomarkers
      of esophageal squamous cell carcinoma.

PMID- 27706657
TI  - Genetic and correlation analysis of oleoresin chemical components in slash pine.
AB  - This is the first comprehensive study of the genetic analysis of the majority of
      oleoresin components of slash pine (Pinus elliottii). Pine oleoresin, the resin
      secreted from the pine tree, is a raw material widely used in industrial
      products. The objective of this study was to explore the genetic variation and
      correlation between the major oleoresin components of 50 open pollinated families
      of slash pine. The individual narrow-sense heritability of the 23 oleoresin
      components and genetic correlations between them were estimated using the
      residual maximum likelihood in the flexible mixed modeling program, ASReml-R. A
      high heritability of 0.424 was observed for beta-pinene. Moderate levels of
      heritability were estimated for beta-phellandrene, methyl abietate, estragole, 15
      hydroxy-dehydroabietic acid, and isopimaric acid methyl ester at 0.303, 0.294,
      0.27, 0.258, and 0.2, respectively. The heritabilities for pimaric acid methyl
      ester, abieta-8, 13-diene-18-oic acid methyl ester, sandaracopimaric acid, methyl
      ester, and camphene were relatively low and ranged from 0.11 to 0.17. Many
      negative genetic correlations were observed as unfavorable while the
      corresponding phenotypic correlations presented no significant relationships or
      positive phenotypic correlations. However, the heritabilities and genetic
      correlations showed that single or multiple component selections and improvement,
      directly or indirectly, were effective. We postulate that genetic parameters
      estimated in this study will work as a reference in breeding programs of
      oleoresin components, especially in slash pine.

PMID- 27706659
TI  - Molecular cloning, overexpression, purification, and sequence analysis of the
      giant panda (Ailuropoda melanoleuca) ferritin light polypeptide.
AB  - The complementary DNA (cDNA) of the giant panda (Ailuropoda melanoleuca) ferritin
      light polypeptide (FTL) gene was successfully cloned using reverse transcription
      polymerase chain reaction technology. We constructed a recombinant expression
      vector containing FTL cDNA and overexpressed it in Escherichia coli using pET28a
      plasmids. The expressed protein was then purified by nickel chelate affinity
      chromatography. The cloned cDNA fragment was 580 bp long and contained an open
      reading frame of 525 bp. The deduced protein sequence was composed of 175 amino
      acids and had an estimated molecular weight of 19.90 kDa, with an isoelectric
      point of 5.53. Topology prediction revealed one N-glycosylation site, two casein
      kinase II phosphorylation sites, one N-myristoylation site, two protein kinase C
      phosphorylation sites, and one cell attachment sequence. Alignment indicated that
      the nucleotide and deduced amino acid sequences are highly conserved across
      several mammals, including Homo sapiens, Cavia porcellus, Equus caballus, and
      Felis catus, among others. The FTL gene was readily expressed in E. coli, which
      gave rise to the accumulation of a polypeptide of the expected size (25.50 kDa,
      including an N-terminal polyhistidine tag).

PMID- 27706658
TI  - Study on quality standards for Chimonanthus nitens.
AB  - Chimonanthus nitens Oliv. is a commonly used traditional Chinese medicine.
      Terpenoids, flavonoids, and coumarins are usually considered its main bioactive
      ingredients. Thus, qualitative and quantitative analyses of these compounds are
      crucial in quality control studies of Chimonanthus nitens. In this study, five
      compounds were identified by double-development thin layer chromatography (TLC)
      and the content of four compounds was determined by high performance liquid
      chromatography; the detection wavelength was set to 344 nm and the column
      temperature was 40 degrees C. All calibration curves showed good linear
      regression (R2 > 0.9995). The average recoveries ranged from 97.06 to 104.44%.
      The RSD was below 4.2%. Four compounds remained stable over 24 h and the relative
      standard deviation (RSD) of the precision of their measurement was less than
      1.5%. The developed method was reproducible, sensitive, and simple, and could be
      used for quality control of Chimonanthus nitens.

PMID- 27706660
TI  - Preliminary study on total protein extraction methods from Enterococcus faecalis
      biofilm.
AB  - Enterococcus faecalis is the major pathogen of post-endodontic disease and
      refractory periapical periodontitis, and recent research on this species has
      focused on its pathogenicity. E. faecalis most often causes disease in the form
      of a biofilm, and total protein expression shows a strong association with its
      virulence. Therefore, the purpose of our study was to explore different methods
      of extracting the total proteins of the E. faecalis (ATCC 33186 standard strain)
      biofilm. The total proteins in the biofilm were extracted using an
      ultrasonication method with varied parameters, including duration, amplitude
      setting, period, and duty cycle. After the optimal conditions of ultrasonication
      were determined based on the protein profile from sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis, the total protein content in the
      biofilm was detected using the bicinchoninic acid assay, Bradford Coomassie
      brilliant blue assay, and Lowry assay, and the results were compared and
      analyzed. The parameters for the optimal conditions of ultrasonication were as
      follows: a processing duration of 2 min, amplitude setting of 20%, and
      ultrasonication period of 4 s at a 50% duty cycle. The total protein content was
      2299.1 mg/dish when measured by the bicinchoninic assay, 3793.8 mg/dish when
      measured by the Bradford Coomassie brilliant blue assay, and 1858.0 mg/dish when
      measured by the Lowry assay. These results demonstrate that the Bradford
      Coomassie brilliant blue assay is a simple and feasible method for use in
      detecting the total protein content in a bacterial biofilm.

PMID- 27706661
TI  - Locally linear embedding and neighborhood rough set-based gene selection for gene
      expression data classification.
AB  - Cancer subtype recognition and feature selection are important problems in the
      diagnosis and treatment of tumors. Here, we propose a novel gene selection
      approach applied to gene expression data classification. First, two classical
      feature reduction methods including locally linear embedding (LLE) and rough set
      (RS) are summarized. The advantages and disadvantages of these algorithms were
      analyzed and an optimized model for tumor gene selection was developed based on
      LLE and neighborhood RS (NRS). Bhattacharyya distance was introduced to delete
      irrelevant genes, pair-wise redundant analysis was performed to remove strongly
      correlated genes, and the wavelet soft threshold was determined to eliminate
      noise in the gene datasets. Next, prior optimized search processing was carried
      out. A new approach combining dimension reduction of LLE and feature reduction of
      NRS (LLE-NRS) was developed for selecting gene subsets, and then an open source
      software Weka was applied to distinguish different tumor types and verify the
      cross-validation classification accuracy of our proposed method. The experimental
      results demonstrated that the classification performance of the proposed LLE-NRS
      for selecting gene subset outperforms those of other related models in terms of
      accuracy, and our proposed approach is feasible and effective in the field of
      high-dimensional tumor classification.

PMID- 27706662
TI  - Dynamics of morphological evolution in experimental Escherichia coli populations.
AB  - Here, we applied a two-stage clonal expansion model of morphological (cell-size)
      evolution to a long-term evolution experiment with Escherichia coli. Using this
      model, we derived the incidence function of the appearance of cell-size
      stability, the waiting time until this morphological stability, and the
      conditional and unconditional probabilities of morphological stability. After
      assessing the parameter values, we verified that the calculated waiting time was
      consistent with the experimental results, demonstrating the effectiveness of the
      two-stage model. According to the relative contributions of parameters to the
      incidence function and the waiting time, cell-size evolution is largely
      determined by the promotion rate, i.e., the clonal expansion rate of selectively
      advantageous organisms. This rate plays a prominent role in the evolution of cell
      size in experimental populations, whereas all other evolutionary forces were
      found to be less influential.

PMID- 27706663
TI  - Building the SeqChromMM Markov property atlas of the human genome by analyzing
      the 200-bp units of the 15 different chromatin regions of ENCODE.
AB  - We analyzed the publicly available ChromHMM BED files of the ENCODE project and
      tested the Markov properties of the different chromatin states in the human
      genome. Nucleotide frequency profiles of regional chromatin segmentations were
      analyzed, and Markov chains were built to detect Markov properties in the
      chromatin states of different ChromHMM regions. By estimating the transition
      probabilities of 200-base pair nucleotide sequences of the human genome, we
      constructed a nucleotide-sequence-based Markovian chromatin map called
      SeqChromMM.

PMID- 27706664
TI  - Nanofibers promote HepG2 aggregate formation and cellular function.
AB  - Formation of hepatocyte spheroids is a necessary strategy for increasing liver
      specific function in vitro. In this study, HepG2 cells showed good viability when
      grown on a polylactic acid-chitosan (PLA-CS) nanofiber and aggregated to form
      multicellular spheroids on the PLA-CS nanofibers with a diameter of approximately
      100-200 mm in 5 days of culture, whereas no such aggregation was observed in
      cells cultured on 24-well plates. Hepatocyte spheroids formed on the PLA-CS
      nanofibers displayed excellent hepatic-related protein expression, such as
      albumin and urea, compared to HepG2 cells cultured on the 24-well plates. These
      results indicated that formation of the hepatocyte spheroids in nanofibers can
      increase and maintain hepatocyte functions for a longer time, supporting a new
      strategy for bioartificial liver development.

PMID- 27706665
TI  - Roles of ERalpha and ERbeta in estrogen-induced DDP chemoresistance in non-small
      cell lung cancer.
AB  - The role of estrogen in inducing chemoresistance is not yet fully understood. The
      objective of this study was to observe the relationship between estrogen levels
      and cellular response to chemotherapeutic drugs in non-small cell lung cancer
      (NSCLC) and to reveal the potential mechanisms involved. Cell viability was
      analyzed after pre-treating NSCLC cells with different levels of estrogen (E2),
      followed by treatment with an anti-tumor drug for 48 h. The roles of various
      estrogen receptors (ERs) were examined in vitro by blocking the activity of each
      ER individually. The ER pathway was further confirmed in NSCLC tissues. It was
      found that 10-1000 nM E2 resulted in a decreased cellular response to DDP in
      H1650 cells compared to the use of cisplatin alone (P < 0.05). However, this
      result was not demonstrated in H1299 cells, which lack p53. Both ERa and ERb were
      associated with E2-induced cisplatin chemoresistance, though they had opposite
      functions. p53 expression did not correlate with the expression of ERa or ERb
      individually. However, a statistically significant correlation between p53
      expression and ERa to ERb mRNA ratio was observed (P < 0.001, R = -0.676). These
      findings suggest that E2-induced DDP chemoresistance depends on the balance
      between ERa and ERb expression and the p53 pathway.

PMID- 27706666
TI  - Anti-nociceptive effects of Paecilomyces hepiali via multiple pathways in mouse
      models.
AB  - Paecilomyces hepiali (PH), a well-known medicinal fungus, has various
      pharmacological efficacies. In our study, the antinociceptive effects of PH and
      underlying mechanisms were evaluated using various mouse models. An acetic acid
      induced writhing test, hot plate test, and formalin test were employed to
      evaluate the antinociceptive activities of PH. The levels of neuronal nitric
      oxide synthase (nNOS) in the hypothalamus and monoamine neurotransmitters in the
      serum and hypothalamus of experimental mice were examined. Additionally, hot
      plate tests using mice pretreated with various antagonists were used to determine
      the mechanisms of PH-mediated antinociception. The PH-enhanced latency period of
      mice in the hot plate test was significantly blocked by pretreatment with
      atropine and glibenclamide. PH shortened the phase I and phase II reaction times
      of formalin-treated mice. Strongly reduced writhing and stretching induced by
      acetic acid were observed in PH-treated mice, indicating that PH mainly exerts
      antinociceptive activity on neurogenic pain. After thermal pain stimulation for
      30 s, compared to control mice, 7-day PH-treated mice had lower nNOS and dopamine
      levels, and increased levels of serotonin in both the serum and hypothalamus.
      Collectively, our data showed that PH mediated antinociceptive activities via
      multiple pathways, including monoamines, nNOS/ATP-sensitive K+ channels, and M
      type acetylcholine receptors.

PMID- 27706667
TI  - Expression and distribution of SP and its NK1 receptor in the brain-gut axis in
      neonatal maternally separated rat model with visceral hypersensitivity.
AB  - Neurokinin-1 receptor (NK1R) is a high affinity Substance P (SP) receptor and
      plays a key role in visceral hypersensitivity in irritable bowel syndrome (IBS).
      Early life stress is a significant risk factor in IBS. The aim of the present
      study was to investigate the influence of neonatal maternal separation on the
      expression and distribution of SP and its receptor along the brain-gut axis in a
      neonatal maternally separated rat model with visceral hypersensitivity. Male
      neonatal Sprague-Dawley rats, 2-21-day old, were randomly distributed into
      maternal separation groups of 3 h daily maternal separation (MS) or non-handling
      (NH). These rats underwent colorectal balloon distention (CRD) upon reaching
      adulthood. Immunofluorescence was used to examine the distal colon, lumbosacral
      spinal cord, and the brainstem to semi-quantitatively determine SP and NK1R
      expression before and after CRD. The following features were assessed: percentage
      SP-positive area in colonic muscle layer, the number of NK1R-positive myenteric
      plexus, SP-positive area and NK1-positivity score in the dorsal horn and the
      brainstem. Neither of these was altered in the MS and NH groups before or after
      CRD. These results suggest that the SP system might play little role in the
      development of visceral hyperalgesia in the neonatal maternal separation rat
      model.

PMID- 27706669
TI  - Gene regulatory network identification from the yeast cell cycle based on a neuro
      fuzzy system.
AB  - Many studies exist for reconstructing gene regulatory networks (GRNs). In this
      paper, we propose a method based on an advanced neuro-fuzzy system, for gene
      regulatory network reconstruction from microarray time-series data. This approach
      uses a neural network with a weighted fuzzy function to model the relationships
      between genes. Fuzzy rules, which determine the regulators of genes, are very
      simplified through this method. Additionally, a regulator selection procedure is
      proposed, which extracts the exact dynamic relationship between genes, using the
      information obtained from the weighted fuzzy function. Time-series related
      features are extracted from the original data to employ the characteristics of
      temporal data that are useful for accurate GRN reconstruction. The microarray
      dataset of the yeast cell cycle was used for our study. We measured the mean
      squared prediction error for the efficiency of the proposed approach and
      evaluated the accuracy in terms of precision, sensitivity, and F-score. The
      proposed method outperformed the other existing approaches.

PMID- 27706668
TI  - Enhancement of dendritic cells with melanoma-associated antigen 3 for inducing
      cytotoxicity by cytotoxic T lymphocytes on bladder cancer BIU-87 cells.
AB  - To determine the cytotoxic effect of lymphocytes activated by melanoma-associated
      antigen 3 (MAGE-3)-sensitized dendritic cells (DCs) on BIU-87 tumor cells, and to
      evaluate the possibility of MAGE-3-peptide-pulsed DCs as a vaccine in bladder
      cancer immunotherapy, the proliferation of T cells and the activity of cytotoxic
      T lymphocytes (CTLs) were examined by the MTT method. CTLs were induced by MAGE-3
      sensitized DCs, or by ovalbumin (OVA) peptide and non-sensitized DCs as controls,
      respectively. The results indicated that MAGE-3-sensitized DCs have the ability
      to promote the proliferation of T cells as well as the cytotoxic activity of CTLs
      on bladder cancer cells in comparison with OVA peptide and non-sensitized DCs. In
      other words, DCs sensitized by the MAGE-3 antigen peptide could obviously
      upregulate the proliferation of T cells, which resulted in the growth inhibition
      of bladder cancer BIU-87 cells. In addition, MAGE-3-sensitized DCs played an
      important role in inhibiting the growth of human BIU-87 tumor xenografts in nude
      mice.

PMID- 27706670
TI  - Using Markov chains of nucleotide sequences as a possible precursor to predict
      functional roles of human genome: a case study on inactive chromatin regions.
AB  - Recent advances in computational epigenetics have provided new opportunities to
      evaluate n-gram probabilistic language models. In this paper, we describe a
      systematic genome-wide approach for predicting functional roles in inactive
      chromatin regions by using a sequence-based Markovian chromatin map of the human
      genome. We demonstrate that Markov chains of sequences can be used as a precursor
      to predict functional roles in heterochromatin regions and provide an example
      comparing two publicly available chromatin annotations of large-scale epigenomics
      projects: ENCODE project consortium and Roadmap Epigenomics consortium.

PMID- 27706671
TI  - Cytotoxicity and DNA damage in mouse macrophages exposed to silica nanoparticles.
AB  - Silica (SiO2) nanoparticles are being progressively applied in various
      applications, including cosmetics, food technology, and medical diagnostics.
      Although crystalline SiO2 is a known carcinogen, the carcinogenicity of SiO2
      nanoparticles remains unclear. Here, we assessed the cytotoxic effects and DNA
      injury induced by exposure to various dosages of SiO2 nanoparticles at 0-2400
      mg/mL (0-3200 mg/mL microscale SiO2 as positive control) for 24 h using RAW264.7
      cells, followed by methyl tetrazolium (MTT) assay. Cells were also treated by
      31.25, 125, and 500 mg/mL SiO2 nanoparticles (500 mg/mL microscale SiO2 as
      positive control) for 24 h and examined by single cell gel electrophoresis assay
      (SCEG) and flow cytometry. Outstanding dose-related decline in cell viability was
      observed with enhancing dosages of SiO2 nanoparticles by MTT assay. The
      inhibitory concentration 50% of SiO2 nanoparticles and microscale SiO2 was 16690
      and 5080 mg/mL, respectively. The comet rate (comet%), length of tail, the
      percentage in DNA tail (TDNA%) and olive tail moment (OTM) induced by SiO2
      nanoparticles were significantly increased in comparison with control and
      microscale SiO2 at 500 mg/mL. 500 mg/mL SiO2 nanoparticles and microscale SiO2
      caused a significant increase in apoptosis rate, decreased proliferation index
      and increased cell proportions in G0/G1 phases by contrast to the negative
      control (P < 0.05). This indicates that SiO2 nanoparticles are more cytotoxic
      than microscale SiO2 particles; they induce DNA injury, increase apoptosis, and
      decrease the proliferation index in RAW264.7 cells. DNA injury and apoptosis may
      be involved in reducing cell proliferation.

PMID- 27706672
TI  - Evaluation of four protein extraction methods for proteomic analysis of mango
      peel.
AB  - The peel of mango (Mangifera indica L.) is a special plant tissue that contains
      many compounds that interfere with protein extraction. A successful separation
      with Two-dimensional electrophoresis (2-DE) is the key step for proteomic
      analysis. To evaluate the efficiencies of mango peel protein extraction for 2-DE,
      four extraction methods were tested: 1) 2-D clean-up kit, 2) trichloroacetic
      acid/acetone precipitation, 3) phenol extraction, 4) phenol with
      methanol/ammonium acetate precipitation. The results showed that the phenol with
      methanol/ammonium acetate precipitation produced the best quality protein
      extraction and separation. Proteins were separated in 30-70 and >70 kDa ranges
      better than with the other methods. Acidic proteins had better resolution with
      fewer horizontal and vertical streaks. Sixteen proteins were identified by
      maxtrix-assisted laser desorption/ ionisation time-of-flight tandem mass
      spectrometry (MALDI-TOF/ TOF-MS/MS). The result demonstrated that each of these
      four methods can be used to prepare mango peel proteins. The phenol with
      methanol/ ammonium acetate precipitation was the best choice for proteomic
      analysis of mango peel.

PMID- 27706673
TI  - Novel single nucleotide polymorphisms in the 5' regulatory region of the duck
      SCD1 gene and their associations with serum biochemical levels and fatty acid
      composition.
AB  - Stearoyl-coenzyme A desaturase 1 (SCD1) is the key limiting enzyme in the
      synthesis of monounsaturated fatty acids, and plays a crucial role in the
      regulation of oleic acid. In this study, 165 ten-week-old Cherry Valley ducks
      were used to investigate single nucleotide polymorphisms (SNPs) in the 5'
      regulatory region of the SCD1 gene, and their associations with duck serum
      biochemical levels and fatty acid composition. Two novel SNPs, g.936516 C > G and
      g.936551 T > C, were found by polymerase chain reaction-single-strand
      conformation polymorphism analysis and DNA sequencing methods, exhibiting six
      genotypes (AA, BB, CC, AB, AC, and BC). The frequency of the dominant genotype BB
      and allele B was 0.321 and 0.403, respectively. The polymorphism information
      content value was 0.617, indicating high polymorphism. The chi-square test
      indicated that the genotype distribution deviated markedly from Hardy-Weinberg
      equilibrium (P < 0.01). The linkage of the two mutant sites in the duck SCD1 gene
      had significant effects on the serum albumin, total protein, globulin,
      triglyceride, total cholesterol, and cholinesterase levels, as well as on 16
      kinds of fatty acids except for C14:1 and C20:0 (P < 0.05). These results
      indicated that the C allele might have a positive effect on polyunsaturated fatty
      acids with potential health benefits. Therefore, the SCD1-gene-specific SNPs in
      the 5' regulatory region may be a useful marker for serum lipid, serum protein,
      and fatty acid composition in future marker-assisted selection for duck breeding.

PMID- 27706674
TI  - Immunological impression cytology of the conjunctival epithelium in patients with
      thyroid orbitopathy-related dry eye.
AB  - Thyroid orbitopathy (TO) is an autoimmune disease that is complicated by ocular
      surface disorders, leading to discomfort. Dry eye is very prevalent in patients
      with TO. Recent studies on the pathogenesis of dry eye have focused on the
      inflammatory process, and some supporting evidence has been discovered. Because
      TO is a disorder of autoimmune origin, we assumed that the association between TO
      and dry eye is related to inflammation. Inflammation of the ocular surface in TO
      related dry eye has not been well studied. In this study, we assessed cellular
      inflammation of the ocular surface and the cytokine profiles in patients with TO
      related dry eye. Conjunctival impression cytology (CIC) was assessed with an
      immunofluorescent assay. TO-related dry eye was diagnosed by using the Schirmer
      test, tear break-up time, thyroid function, and clinical signs. CIC was combined
      with immunological staining of interleukin-1a (IL-1a), IL-1b, and IL- 6. The
      immunological impression cytology (IC) grade was compared to the clinical
      activity score of TO. All TO patients with dry eye were positive for IL-1a, IL
      1b, and IL-6. However, the normal controls were also positive for IL-1a. A trend
      was observed between the clinical inflammatory score and immunological IC grade.
      This study was the first to delineate the immunological IC of TO-related dry eye.
      Our study aimed to investigate the pathogenesis of dry eye in TO. Our findings
      suggest that the conjunctival cytokines IL-1a, IL-1b, and IL-6 may play a role.
      The results of this study will be useful for future studies of additional
      inflammatory cytokines, and the levels of these cytokines could be used as an
      outcome to assess the efficacy of treatment, such as anti-cytokine or
      immunosuppression therapy, in patients with TO-related dry eye or other ocular
      surface inflammatory disorders.

PMID- 27706675
TI  - Letter to the Editor "Drosha, DGCR8, and Dicer mRNAs are downregulated in human
      cells infected with dengue virus 4" - Genet. Mol. Res. 15 (2): gmr.15027891 -
      Drosha, Dicer, and TRBP mRNA are downregulated in Vero cells with the 3'UTR of
      Dengue virus.
AB  - Dear Editor, A recent paper (Casseb et al., 2016) published in the journal
      Genetics and Molecular Research described the interesting concept that dengue
      virus (DENV)-4 infection, in the human cell line A-549, leads to the
      downregulation of expression of key components of microRNA (miRNA) biogenesis,
      such as Drosha, Dicer, and DGCR8. For this, the authors performed a time course
      infection of A-549 cells for 5 days. The highest viral load was observed at 3
      days post-infection, which corresponded with the maximum downregulation of
      expression of Drosha, Dicer, and DGCR8, assayed by quantitative PCR (RT-qPCR).
      These results supported the recent notion of a complex interaction between DENV
      and the host miRNA machinery and of the host miRNA response to this particular
      infection. Extensive evidence has shown that DENV can take advantage of host
      miRNAs for its own replication (Zhu et al., 2014) and that host miRNAs can
      inhibit DENV replication (Wu et al., 2013).

PMID- 27706676
TI  - Effect of compound Maqin decoction on TGF-beta1/Smad proteins and IL-10 and IL-17
      content in lung tissue of asthmatic rats.
AB  - In this research, compound Maqin decoction (CMD) has been shown to positively
      affect in airway inflammation of asthma models. We evaluated the effects of CMD
      on the expression of transforming growth factor (TGF)-beta1/Smad proteins,
      interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was
      induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats
      were killed to evaluate the expression of TGF-beta1 and Smad proteins in lung
      tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by
      ELISA. The expression of TGF-beta1 and Smad3 protein increased, whereas
      expression of Smad7 protein decreased upon high-dose or low-dose treatment with
      CMD or by intervention with dexamethasone, compared to the control. There was a
      significant difference between treatment with a high dose CMD and the control
      treatment, but no significant difference was found between high-dose CMD
      treatment and dexamethasone intervention. The expression of TGF-beta1 and Smad7
      protein increased, whereas the expression of Smad3 protein decreased in the model
      group compared to other groups. In the CMD high-dose group, low-dose group, and
      dexamethasone intervention group, the IL-17 concentrations in lung tissue
      homogenates were decreased, while IL-10 levels were increased. Again, there was a
      significant difference between CMD high-dose and control treatment, but not
      between CMD high-dose treatment and dexamethasone intervention. Thus, positive
      effects of CMD against asthmatic airway remodeling may be due to its regulatory
      effect on TGF-beta1, Smad3, and Smad7 protein levels and on cytokines such as IL
      10 and IL-17.

PMID- 27706677
TI  - Effect of miR-29c and miR-129-5p on epithelial-mesenchymal transition in
      experimental biliary atresia mouse models.
AB  - Biliary atresia (BA) is a destructive bile duct disease occurring in newborn
      children within a few weeks after birth. In this study, the effect of miR-29c and
      miR-129-5p on epithelial-mesenchymal transition (EMT) in experimental BA was
      explored by constructing BA mouse models via Rhesus rotavirus vaccine infection.
      miR-29c and miR-129-5p expression was analyzed by real-time quantitative
      polymerase chain reaction. EMT was established by induction with transforming
      growth factor (TGF)-beta1. miR-29c and miR-129-5p were overexpressed and
      inhibited, respectively, by Lipofectamine transfection. EMT-related protein
      (formin-like 2, FMNL2; E-cadherin; vimentin; and cytokeratin-19, CK-19)
      expression was analyzed by western blot and immunofluorescent assay. The results
      indicated that miR-29c and miR-129-5p were downregulated and upregulated in BA
      mice. TGF-beta1 induction caused a time-dependent decrease and increase in miR
      29c and miR-129-5p, respectively. Additionally, TGF-beta1 induced an increase in
      FMNL2 and vimentin expression and a decrease in E-cadherin and CK-19 expression
      (P < 0.05). Overexpression or suppression of miRNA-29c or miR-129-5p,
      respectively, induced the inhibition of FMNL2 and vimentin, and promotion of E
      cadherin and CK-19 expression, in the test groups compared to the non
      intervention group (P < 0.05). However, the FMNL2, vimentin, E-cadherin, and CK-
      19 expression did not differ between the control and non-intervention groups (P >
      0.05). Thus, miR-29c upregulation or miR-129-5p downregulation effectively
      prevented EMT in BA by regulating the expression of EMT pathway-related proteins.
      Therefore, miR-29c and miR-129-5p could be utilized as therapeutic targets for BA
      in the future.

PMID- 27706678
TI  - Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-kappaB
      pathway and epithelial-mesenchymal transition.
AB  - The aim of this study was to investigate the expression of T-cell immunoglobulin
      mucin domain molecule-3 (Tim-3) in osteosarcoma tissues, and analyze its effect
      on cell proliferation and metastasis in an osteosarcoma cell line. Tim-3 mRNA and
      protein expression in osteosarcoma tissue was detected by reverse transcriptase
      polymerase chain reaction and immunohistochemistry, respectively. Additionally,
      the cell viability, apoptosis rate, and invasive ability of the osteosarcoma cell
      line MG-63 were tested using the methyl thiazolyl tetrazolium assay, Annexin V
      propidium iodide flow cytometry, and a Transwell assay, respectively, following
      Tim-3 interference using small interfering RNA (siRNA). We also analyzed the
      expression of Snail, E-cadherin, vimentin, and nuclear factor (NF)-kB in the
      cells by western blot. We observed that Tim-3 mRNA and protein was significantly
      overexpressed in osteosarcoma tissues, compared to the adjacent normal tissue (P
      < 0.01). Moreover, MG-63 cells transfected with the Tim-3 siRNA presented lower
      cell viability, a greater number of apoptotic cells, and decreased invasive
      ability (P < 0.01), compared to control cells. Additionally, we observed a
      decrease in Snail and vimentin expression, an increase in the E-cadherin level,
      and an increase in NF-kB p65 phosphorylation (P < 0.01) in Tim-3 siRNA
      transfected MG-63 cells. Based on these results, we concluded that Tim-3 is
      highly expressed in osteosarcoma tissue. Moreover, we speculated that interfering
      in Tim-3 expression could significantly suppress osteosarcoma cell (MG-63)
      proliferation and metastasis via the NF-kB/Snail signaling pathway and epithelial
      mesenchymal transition.

PMID- 27706679
TI  - Association of single-nucleotide polymorphisms, rs2235371 and rs2013162, in the
      IRF6 gene with non-syndromic cleft palate in northeast China.
AB  - The aim of this study was to determine the association between two SNPs
      (rs2235371 and rs2013162) in the interferon regulatory factor 6 (IRF6) gene and
      non-syndromic cleft palate (NSCP) in northeast China. We genotyped these two SNPs
      in 104 NSCP cases, as well as in 178 parents and 300 controls. Case-control and
      case-parent analyses were performed using chi2 tests and family-based association
      tests (FBAT). Results indicated that there were significant differences in both
      genotypic and allelic distributions between patients and controls at rs2235371
      and rs2013162 in the IRF6 gene. Case-parent analysis revealed over-transmission
      of the C allele in rs2235371 and the A allele in rs2013162. Lastly, FBAT showed
      over-transmission of the CA haplotype. This study demonstrated that the two SNPs,
      rs2235371 and rs2013162, are strongly associated with NSCP in the northeast
      Chinese population.

PMID- 27706680
TI  - Association between TXNRD1 polymorphisms and anti-tuberculosis drug-induced
      hepatotoxicity in a prospective study.
AB  - Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse
      reaction to anti-tuberculosis (TB) treatment. Thioredoxin reductase 1 (TXNRD1),
      encoded by the TXNRD1 gene, is an important enzyme involved in oxidant challenge.
      TXNRD1 plays a key role in regulating cell growth and transformation, and
      protects cells against oxidative damage. We investigated the association between
      TXNRD1 polymorphisms and ATDH susceptibility. In this prospective study, 280
      newly diagnosed TB patients were followed-up for 3 months after beginning anti-TB
      therapy. Tag single-nucleotide polymorphisms (tag-SNPs) of TXNRD1 were selected
      using Haploview 4.2 based on the HapMap database of the Chinese Han in Beijing
      (CHB) panel. Genotyping was performed using the MassARRAY platform. Of the 280
      patients enrolled in this study, 33 were lost to follow-up, 24 had ATDH, and 223
      were free from ATDH. After adjusting for sex, age, smoking status, and body mass
      index, there were no significant differences in the allele and genotype frequency
      distributions of TXNRD1 SNPs between the ATDH and non-ATDH groups (all P > 0.05).
      The haplotype analysis showed that haplotype TCAGCC was associated with an
      increased risk of ATDH susceptibility [P = 0.024, OR (95%CI) = 6.273 (1.023
      38.485)]. Further stratified analyses showed that the haplotype TCAGCC was
      associated with ATDH susceptibility in female subjects [P = 0.036, OR (95%CI) =
      5.711 (0.917-35.560)] and non-smokers [P = 0.029, OR (95%CI) = 6.008 (0.971
      37.158)]. Our results suggest that TXNRD1 variants may favor ATDH susceptibility
      in females and non-smokers. Further studies are required to verify this
      association.

PMID- 27706681
TI  - Reversal of cisplatin resistance in non-small cell lung cancer stem cells by
      Taxus chinensis var.
AB  - Drug resistance in cells is a major impedance to successful treatment of lung
      cancer. Taxus chinensis var. inhibits the growth of tumor cells and promotes the
      synthesis of interleukins 1 and 2 and tumor necrosis factor, enhancing immune
      function. In this study, T. chinensis var.-induced cell death was analyzed in
      lung cancer cells (H460) enriched for stem cell growth in a defined serum-free
      medium. Taxus-treated stem cells were also analyzed for Rhodamine 123 (Rh-123)
      expression by flow cytometry, and used as a standard functional indicator of MDR.
      The molecular basis of T. chinensis var.-mediated drug resistance was established
      by real-time PCR analysis of ABCC1, ABCB1, and lung resistance-related protein
      (LRP) mRNA, and western blot analysis of MRP1, MDR1, and LRP. Our results
      revealed that stem cells treated with higher doses of T. chinensis var. showed
      significantly lower growth inhibition rates than did H460 cells (P < 0.05). The
      growth of stem and H460 cells treated with a combination of T. chinensis var. and
      cisplatin was also significantly inhibited (P < 0.05). Rh-123 was significantly
      accumulated in the intracellular region and showed delayed efflux in stem cells
      treated with T. chinensis var. (P < 0.05), compared to those treated with
      verapamil. T. chinensis var.-treated stem cells showed significant downregulation
      of the ABCC1, ABCB1, and LRP mRNA and MRP1, MDR1, and LRP (P < 0.05) compared to
      H460 cells. Thus, T. chinensis var.-mediated downregulation of MRP1, MDR1, and
      LRP might contribute to the reversal of drug resistance in non-small cell lung
      cancer stem cells.

PMID- 27706682
TI  - Effects of ginsenoside Rg1 on the senescence of vascular smooth muscle cells.
AB  - The development of age-related cardiovascular disease is associated with the
      senescence of vascular cells. This study aimed to investigate the effect of
      ginsenoside Rg1 on vascular smooth muscle cell (VSMC) senescence. Primary VSMCs
      were cultured and divided into control, D-galactose (D-gal), Rg1-L, and Rg1-H
      groups, which were cultured without and with D-gal, and with low- and high
      concentrations of Rg1, respectively. D-gal-induced cellular senescence was
      identified by b-galactosidase staining, and ultrastructural changes within the
      cells were observed. The expression of p16, p21, and p53 in the four groups of
      VSMCs was determined by western blotting, and the cell cycle was investigated by
      flow cytometry. Compared with the control group, there was an obvious change in
      the ultrastructure of VSMCs in the D-gal group, and the proportion of b
      galactosidase-positive cells was significantly increased (P < 0.05). In addition,
      p16, p21, and p53 expression was significantly increased (P < 0.05) and the cell
      cycle was arrested in the G0/G1 phase. Compared with the D-gal group, the
      percentage of positive cells was significantly reduced (P < 0.05) in the Rg1
      groups, the expression of p16, p21, and p53 was significantly reduced (P < 0.05),
      and the number of cells in the G0/G1 phase decreased (P < 0.05). Ginsenoside Rg1
      can inhibit VSMC senescence, and the mechanisms may be related to its partial
      inhibition of the p16INK4a/Rb and p53-p21Cip1/Waf1 signaling pathways during the
      cell cycle.

PMID- 27706683
TI  - Association of polymorphisms in growth hormone and leptin candidate genes with
      live weight traits of Brahman cattle.
AB  - Polymorphisms in candidate genes can produce significant and favorable changes in
      the phenotype, and therefore are useful for the identification of the best
      combination of favorable variants for marker-assisted selection. In the present
      study, an assessment to evaluate the effect of 11 single nucleotide polymorphisms
      (SNPs) in candidate genes on live weight traits of registered Brahman cattle was
      performed. Data from purebred bulls were used in this assessment. The dataset
      included birth (BW), weaning (WW), and yearling (YW) weights. A panel of 11 SNP
      markers, selected by their formerly reported or apparent direct and indirect
      association with live weight traits, was included in an assessment previously
      confirming their minimum allele frequency (<0.05). Live weights were adjusted BW
      (aBW), WW (aWW), and YW (aYW) using a generalized linear model, which included
      the fixed effects of herd and season of birth and the random effect of the sire
      and year of birth. An SNP in a growth hormone gene (GH4.1) was significantly
      related to aWW (P = 0.035) with an estimate substitution effect of 3.97 kg (P =
      0.0210). In addition, a leptin SNP (LEPg.978) was significantly associated with
      aYW (P = 0.003) with an estimate substitution effect of 9.57 kg (P = 0.0007). The
      results suggest that markers GH4.1 and LEPg.978 can be considered as candidate
      loci for assisted genetic improvement programs in Mexican Brahman cattle.

PMID- 27706685
TI  - Polymorphic microsatellite markers for the endangered fish, the slender shiner
      Pseudopungtungia tenuicorpa and cross-species amplification across five related
      species.
AB  - The slender shiner Pseudopungtungia tenuicorpa (Cypriniformes; Cyprinidae;
      Gobioninae) is an endangered freshwater fish species endemic to Korea. The
      current strategies for its conservation involve the study of population genetic
      characters and identification of management units. These strategies require
      suitable molecular markers to study genetic diversity and genetic structure.
      Here, we developed nine polymorphic microsatellite markers for P. tenuicorpa for
      the first time by applying an enrichment method from a size-selected genomic
      library. The developed microsatellite markers produced a total of 101 alleles
      (average 11.2). The observed and expected heterozygosities averaged 0.805 and
      0.835, respectively. Among the nine identified markers, five markers showed
      successful amplification across five related Korean Gobioninae species. Thus, the
      microsatellite markers developed in this study will be useful to establish
      conservation strategies for both P. tenuicorpa and other related species.

PMID- 27706684
TI  - Effects of DNA methyltransferase inhibitor RG108 on methylation in buffalo adult
      fibroblasts and subsequent embryonic development following somatic cell nuclear
      transfer.
AB  - Buffalo are characteristic livestock of the Guangxi Zhuang Autonomous Region of
      China, but their low reproductive capacity necessitates the use of somatic cell
      nuclear transfer (SCNT). We investigated the effects of RG108 on DNA methylation
      in buffalo adult fibroblasts, and on subsequent SCNT embryo development. RG108
      treatment (0, 5, 10, 20, and 100 mM) had no effect on cell morphology, viability,
      or karyotype (2n = 48), and cell growth followed a typical "S" curve.
      Immunohistochemistry showed that relative DNA methylation gradually decreased as
      RG108 concentration increased, and was significantly lower in the 20 and 100 mM
      groups compared to the 0, 5, and 10 mM treatments (0.94 +/- 0.03 and 0.92 +/-
      0.05 vs 1.0 +/- 0.02, 0.98 +/- 0.05, and 0.98 +/- 0.09, respectively; P < 0.05).
      Quantitative polymerase chain reaction revealed that DNMT1 gene expression of
      fibroblasts administered 10, 20, and 100 mM RG108 was significantly lower than
      those in the 0 and 5 mM groups (0.2 +/- 0.05, 0.18 +/- 0.07, and 0.3 +/- 0.09 vs
      1.0 +/- 0.12 and 1.4 +/- 0.12, respectively; P < 0.05). Treatment with 20 mM
      RG108 resulted in the lowest expression levels. Fibroblasts incubated with 20 mM
      RG108 for 72 h were used as donor cells to generate SCNT embryos. A greater
      number of such embryos developed into blastocysts compared to the non-treated
      group (28.9 +/- 3.9 vs 15.3 +/- 3.4%; P < 0.05). RG108 treatment can modify DNA
      methylation in buffalo adult fibroblasts and promote development of subsequent
      SCNT embryos.

PMID- 27706686
TI  - Identification and characterization of SREBF2 expression and its association with
      chicken carcass traits.
AB  - The sterol regulatory element-binding transcription factor 2 gene (SREBF2) plays
      an important role in regulating lipid homeostasis. To reveal the genetic factors
      that underlie carcass fat deposition in chickens, we cloned the coding DNA
      sequence of chicken SREBF2, investigated SREBF2 mRNA expression levels in various
      tissues, detected single nucleotide polymorphisms (SNPs) in the exon regions of
      the gene, and conducted association analyses between single markers/haplotypes
      and carcass traits. The entire 2859-bp cDNA sequence of chicken SREBF2 that
      encoded 952 amino acids was obtained and characterized. SREBF2 mRNA was highly
      expressed in the uropygial gland, followed by the liver, breast muscle, and leg
      muscle. Ten SNPs were detected, and four (g.49363077T>A, g.49357503C>T,
      g.49355533G>A, and g.49354641G>A) were novel. When analyzing the associations
      between the single mutations and carcass traits, significant differences were
      found in three SNPs and g.49357915G>A was highly significantly associated with
      most carcass traits, except for abdominal fat weight and sebum thickness. In
      addition, haplotype combinations that were constructed using the SREBF2 SNPs were
      associated with breast muscle weight. Chickens with the combined genotype H21H21
      had the highest live weight, carcass weight, eviscerated weight, and semi
      eviscerated weight values. To the best of our knowledge, this is the first study
      conducted on chicken SREBF2 polymorphisms, which are predictive of the genetics
      that underlie the economic performance of chickens.

PMID- 27706687
TI  - Antimutagenicity and antigenotoxicity of Aloe arborescens Miller and Aloe
      barbadensis Miller in Aspergillus nidulans and Wistar rats.
AB  - Medicinal plants such as Aloe arborescens Miller and Aloe barbadensis Miller are
      used by the general population to treat various diseases. Therefore, the aim of
      this study was to evaluate the antimutagenicity of these two species using a
      methG1 system in Aspergillus nidulans and the comet assay in rats. The animals
      were treated with the plants at concentrations of 360 and 720 mg/kg body weight
      (1 and 2, respectively) by gavage for 14 days, followed by the administration of
      etoposide on treatment day 8. Blood samples were prepared for analysis of DNA
      damage. For the test in A. nidulans, the biA1methG1 lineage conidia were treated
      for 4 h with both plant species at concentrations of 4 and 8% (w/v). Then, they
      were washed and plated on a selective medium for frequency analysis of survival
      and mutation. The results of the comet assay showed that both plants were
      antigenotoxic compared to etoposide, which was not a typical response of methG1
      systems, where only the highest concentration of plant extracts usually exhibit
      beneficial effects. This study demonstrates the potential antigenotoxicity and
      antimutagenicity of the Aloe plants tested and, therefore, supports their use as
      a form of preventive therapy and for health maintenance by the population.

PMID- 27706688
TI  - Role of ABCB1 C1236T, G2677T, and C3435T genetic polymorphisms in the development
      of acute leukemia in a Chinese population.
AB  - We carried out a case-control study to examine the relationship between the ATP
      binding cassette subfamily B member 1 (ABCB1) gene polymorphisms C1236T, G2677T,
      and C3435T and risk of acute leukemia in a Chinese population. Between May 2013
      and April 2015, we recruited 164 acute leukemia patients and 285 healthy
      controls, and determined polymorphism genotypes by polymerase chain reaction
      restriction fragment length polymorphism. Using unconditional logistic regression
      analysis, we observed that in comparison to the wild-type sequence, the TT
      genotype [odds ratio (OR) = 2.15, 95% confidence interval (CI) = 1.12-4.10; P =
      0.01] and the T allele (OR = 1.39, 95%CI = 1.05-1.86; P = 0.02) of ABCB1 G2677T
      were associated with acute leukemia susceptibility. The TT genotype (OR = 2.03,
      95%CI = 1.11- 3.69; P = 0.01) and the T allele (OR = 1.39, 95%CI = 1.05-1.85; P =
      0.02) of the C3435T polymorphism also increased acute leukemia risk compared to
      the wild-type form. However, no significant relationship was established between
      the ABCB1 C1236T variant and this disease. Our results suggest that the ABCB1
      G2677T and C3435T sequence variations may affect susceptibility to acute
      leukemia.

PMID- 27706689
TI  - Comparative analysis of soybean genotype resistance to Heterodera glycines and
      Meloidogyne species via resistance gene analogs.
AB  - Nematodes are important pests of soybean throughout the world and cause high
      yield losses. As a control strategy, the identification of resistance genes is an
      important aim of breeding studies. Plants possess resistance genes (R), which are
      responsible for the recognition of pathogens and activation of the defense
      system. R genes and resistance gene analogs (RGAs) possess conserved domains,
      from which nucleotide-binding site is the most common. Using degenerate primers
      originating from these domains, it is possible to identify and isolate sequences
      of R and RGA genes. In this study, soybean genotypes resistant to the nematodes
      Heterodera glycines, Meloidogyne incognita, M. javanica, and M. enterolobii were
      compared by the use of RGAs and simple sequence repeat (SSR) markers. Forty-six
      soybean genotypes were studied, including plant introductions (PIs), commercial
      crops, and source of resistance genotypes. Thirteen combinations of RGA primers
      and different SSRs linked to QTLs were used to confirm resistance to soybean cyst
      nematodes (SCN). Fragments associated with resistance to the studied nematodes
      were amplified in the source of resistance and PI genotypes. RGA markers were
      efficient at distinguishing groups of genotypes that were resistant and
      susceptible to Meloidogyne spp and SCN. Combinations of specific primers were
      identified through their ability to amplify nucleotide sequences from possible
      resistance candidate genes. SSR markers contributed to the analysis of SCN race
      specificity, showing that the QTLs identified by these markers are distinct from
      those identified by RGA markers.

PMID- 27706690
TI  - Effects of intra-articular injection of mesenchymal stem cells associated with
      platelet-rich plasma in a rabbit model of osteoarthritis.
AB  - The current study aims to evaluate the macroscopic and histological effects of
      autologous mesenchymal stem cells (MSC) and platelet-rich plasma on knee
      articular cartilage regeneration in an experimental model of osteoarthritis.
      Twenty-four rabbits were randomly divided into four groups: control group,
      platelet-rich plasma group, autologous MSC undifferentiated group, and autologous
      MSC differentiated into chondrocyte group. Collagenase solution was used to
      induce osteoarthritis, and treatments were applied to each group at 6 weeks
      following osteoarthritis induction. After 60 days of therapy, the animals were
      euthanized and the articular surfaces were subjected to macroscopic and
      histological evaluations. The adipogenic, chondrogenic, and osteogenic
      differentiation potentials of MSCs were evaluated. Macroscopic and histological
      examinations revealed improved tissue repair in the MSC-treated groups. However,
      no difference was found between MSC-differentiated and undifferentiated
      chondrocytes. We found that MSCs derived from adipose tissue and platelet-rich
      plasma were associated with beneficial effects in articular cartilage
      regeneration during experimental osteoarthritis.

PMID- 27706692
TI  - Association of ectomycorrhizal fungi with Picea crassifolia (Pinaceae, Piceoidae)
      from high-altitude stands in Mount Helan Nature Reserve, China.
AB  - We investigated the diversity of ectomycorrhiza associated with the endemic Picea
      crassifolia in Mount Helan National Nature Reserve in Inner Mongolia, China.
      Toward this objective, we conducted morphological and molecular identification of
      ectomycorrhizae in soil cubes taken from pure P. crassifolia stands. Eleven types
      of ectomycorrhizal (ECM) organisms were separated, briefly described, and
      identified. Nine morphotypes belonged to the phylum Basidiomycotina [Amphinema
      byssoides, Cortinarius sp (cf. limonius), Cortinarius vernus, Inocybe cf.
      nitidiscula, Inocybe sp 1, Sebacina incrustans, Sebacina sp, Suillus luteus, and
      Piceirhiza tuberculata x Picea crassifolia (comb. Nov.)], and two morphotypes to
      the phylum Ascomycotina (Cenococcum geophilum and Helvella sp). The diversity of
      ECM organisms in P. crassifolia was lower than that reported by other studies on
      spruce or pine forests, or on sporocarp diversity in the high-mountain forests of
      China. Most of the fungi in the rhizosphere did not correspond to species
      previously recorded as sporocarps above ground. Here, several new ectomycorrhiza
      morphotypes are proposed and described. We also confirmed the ectomycorrhizal
      status of the genus Sebacina (order Sebacinales).

PMID- 27706691
TI  - Discovery of differentially expressed genes in cashmere goat (Capra hircus) hair
      follicles by RNA sequencing.
AB  - The mammalian hair follicle (HF) is a unique, highly regenerative organ with a
      distinct developmental cycle. Cashmere goat (Capra hircus) HFs can be divided
      into two categories based on structure and development time: primary and
      secondary follicles. To identify differentially expressed genes (DEGs) in the
      primary and secondary HFs of cashmere goats, the RNA sequencing of six
      individuals from Arbas, Inner Mongolia, was performed. A total of 617 DEGs were
      identified; 297 were upregulated while 320 were downregulated. Gene ontology
      analysis revealed that the main functions of the upregulated genes were electron
      transport, respiratory electron transport, mitochondrial electron transport, and
      gene expression. The downregulated genes were mainly involved in cell autophagy,
      protein complexes, neutrophil aggregation, and bacterial fungal defense
      reactions. According to the Kyoto Encyclopedia of Genes and Genomes database,
      these genes are mainly involved in the metabolism of cysteine and methionine, RNA
      polymerization, and the MAPK signaling pathway, and were enriched in primary
      follicles. A microRNA-target network revealed that secondary follicles are
      involved in several important biological processes, such as the synthesis of
      keratin-associated proteins and enzymes involved in amino acid biosynthesis. In
      summary, these findings will increase our understanding of the complex molecular
      mechanisms of HF development and cycling, and provide a basis for the further
      study of the genes and functions of HF development.

PMID- 27706693
TI  - Role of ADH2 and ALDH2 gene polymorphisms in the development of Parkinson's
      disease in a Chinese population.
AB  - In this study, we investigated the role of ADH2 Arg47His and ALDH2 Glu487Lys
      genetic polymorphisms in the development of Parkinson's disease in a Chinese
      population. Between January 2013 and May 2014, 115 patients with Parkinson's
      disease and 214 healthy controls were recruited in our study. Genotyping of ADH2
      Arg47His and ALDH2 Glu487Lys polymorphisms was performed by the polymerase chain
      reaction-restriction fragment length polymorphism method. In the dominant model,
      the GA + AA genotype of ALDH2 Glu487Lys was found to be significantly associated
      with elevated risk of Parkinson's disease when compared with the GG genotype
      [odds ratio = 1.71, 95% confidence interval (CI) = 1.02-2.84]. In the recessive
      model, the AA genotype of ALDH2 Glu487Lys showed a 4.87-fold increase (95%CI =
      1.54-18.03) in the risk of Parkinson's disease when compared to the GG and GA
      genotypes. However, no significant association was found between the ADH2
      Arg47His polymorphism and risk of Parkinson's disease in the co-dominant,
      dominant, or recessive models. In conclusion, our study suggests that the ALDH2
      polymorphism could influence the development of Parkinson's disease in the
      Chinese population studied here.

PMID- 27706694
TI  - Effect of organic matter enrichment on the fungal community in limestone cave
      sediments.
AB  - Caves are considered major touristic attractions. The management plans of many
      such caves include limiting the number of visitors; however, the human impact on
      microbial communities within caves is rarely considered. Therefore, the aim of
      this study was to evaluate the impact of human-transferred organic matter on the
      fungal microcosms growing on cave sediments. Samples were collected from a
      Brazilian limestone cave and cultured with 0.25 or 0.5% 1:1 (w/w) beef and yeast
      extract (simulating organic matter) under laboratory conditions. The contaminated
      fungal community was then evaluated at days 0, 30, 180, and 365 after inoculation
      by polymerase chain reaction denaturing gradient gel electrophoresis. We observed
      changes in the fungal communities with time, as well as the concentration of
      added organic matter, compared to the control fungal communities. Additionally,
      the contaminated microcosms showed a greater number of operational taxonomic
      units compared to the controls. These findings suggest that tourist activity
      could cause fungal outbreaks of possible human pathogens, demonstrating the
      importance of fungal monitoring in these caves.

PMID- 27706695
TI  - Effect of polychlorinated biphenyls on oxidation stress in the liver of juvenile
      GIFT, Oreochromis niloticus.
AB  - The present study clearly showed that chronic exposure to polychlorinated
      biphenyls (PCBs) at environmentally relevant concentrations can damage juvenile
      tilapia livers by modulating antioxidant enzyme activities and gene
      transcription, which affects toxic bioaccumulation and histological congestion.
      The results suggest that PCBs caused a decrease in the activity of some hepatic
      antioxidative and biotransformation enzymes (SOD, CAT, GST, T-GSH, and MDA) in
      tilapia at 7 days, as well as transcriptional changes (sod, cat, and gst). Except
      for some antioxidant parameters (T-GSH, GSH/GSSG, T-AOC, and MDA), significant
      declines and increases occurred at 14 and 21 days, respectively. Most of the
      antioxidant enzymatic signatures and genotoxicity significantly increased at 14
      and 21 days. This study presented evidence that PCBs could result in hepatic
      toxicity through oxidative stress in the early growth stages of tilapia, and we
      speculated that oxidative stress plays an important role in embryonic
      developmental toxicity induced by PCBs.

PMID- 27706696
TI  - Genetic diversity in cassava landraces grown on farms in Alta Floresta-MT,
      Brazil.
AB  - Brazil is considered one of the domestication centers of cassava (Manihot
      esculenta), containing a large part of the biological diversity and traditional
      knowledge of the species. The aim of the present study was to evaluate the
      genetic diversity of cassava landraces grown by farmers in the north of Mato
      Grosso State, Brazil, using inter simple sequence repeat (ISSR) molecular
      markers. The study was carried out in the municipality of Alta Floresta, MT, on
      farms located in two rural areas. Seventeen cassava landraces were selected. The
      DNA was extracted and polymerase chain reaction amplifications were performed
      using 15 ISSR primers. Genetic similarity estimates were calculated using
      Jaccard's index and the generated matrix was used for clustering the genotypes by
      using UPGMA and Tocher's methods. The 15 ISSR primers amplified 120 fragments,
      revealing 61.67% polymorphism. The polymorphism information content ranged from
      0.04 to 0.61, averaging 0.39. The most similar genotypes were AF5 and AF8,
      whereas the least similar were AF1 and AF16. The UPGMA clustering method formed
      five groups. Group I included twelve landraces, Group II contained two, and the
      other groups contained one landrace each. Tocher's method resulted in six groups:
      12 landraces clustered in one group, and the other groups each contained one
      landrace. The ISSR markers proved efficient in revealing genetic diversity among
      the cassava landraces. The landraces grown by farmers in the two rural areas of
      Alta Floresta have a great variability and, thus, can be exploited in programs
      for breeding and preservation of the species.

PMID- 27706697
TI  - Effect of polychlorinated biphenyls on osmoregulatory response and apoptosis in
      GIFT tilapia, Oreochromis niloticus.
AB  - In the present study, GIFT tilapia Oreochromis niloticus were exposed to
      polychlorinated biphenyls (PCBs) for 7, 14, and 21 days. Over the duration of the
      exposure, genotoxicity and the activity of Na+/K+-ATPase (NKA) and Ca+/Mg+-ATPase
      (CMA) were measured in the gill, kidney, and intestine, to evaluate changes in
      osmoregulatory response in O. niloticus. Our results showed significant decreases
      in organic NKA (except in gill tissues after 0.5 mg/L PCB-exposure) and CMA
      activity. The results of the genotoxicity assay showed significant increases in
      atp1a1a, nkcc2 (only in gill tissue), and fxyd7 (except after 21 days of 5 mg/L
      PCB exposure). We found significant increases in caspase proteins in the liver in
      the 5-mg/L PCB exposure group, and the transcripts showed dose-dependent
      increases between treatment groups over the exposure duration. This study
      presents evidence that chronic exposure to PCB could result in organic
      osmoregulatory response and hepatic apoptosis in GIFT tilapia.

PMID- 27706698
TI  - Genetic potential of common bean progenies obtained by different breeding methods
      evaluated in various environments.
AB  - Grain yield is strongly influenced by the environment, has polygenic and complex
      inheritance, and is a key trait in the selection and recommendation of cultivars.
      Breeding programs should efficiently explore the genetic variability resulting
      from crosses by selecting the most appropriate method for breeding in segregating
      populations. The goal of this study was to evaluate and compare the genetic
      potential of common bean progenies of carioca grain for grain yield, obtained by
      different breeding methods and evaluated in different environments. Progenies
      originating from crosses between lines and CNFC 7812 and CNFC 7829 were replanted
      up to the F7 generation using three breeding methods in segregating populations:
      population (bulk), bulk within F2 progenies, and single-seed descent (SSD).
      Fifteen F8 progenies per method, two controls (BRS Estilo and Perola), and the
      parents were evaluated in a 7 x 7 simple lattice design, with plots of two 4-m
      rows. The tests were conducted in 10 environments in four States of Brazil and in
      three growing seasons in 2009 and 2010. Genetic parameters including genetic
      variance, heritability, variance of interaction, and expected selection gain were
      estimated. Genetic variability among progenies and the effect of progeny
      environment interactions were determined for the three methods. The breeding
      methods differed significantly due to the effects of sampling procedures on the
      progenies and due to natural selection, which mainly affected the bulk method.
      The SSD and bulk methods provided populations with better estimates of genetic
      parameters and more stable progenies that were less affected by interaction with
      the environment.

PMID- 27706699
TI  - Increased miR-155-5p expression in dermal mesenchymal stem cells of psoriatic
      patients: comparing the microRNA expression profile by microarray.
AB  - Mesenchymal stem cells (MSCs) have pleiotropic immuno-modulatory effects and pro
      angiogenic ability, leading to the presumption that MSCs may be involved in the
      pathogenesis of many inflammatory or autoimmune disorders, including psoriasis.
      In a previous study, we reported the specific gene expression profile of dermal
      MSCs from psoriasis. Inflammation- and angiogenesis-related genes, such as
      lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor
      (LITAF), dual-specificity protein phosphatase 1 (DUSP1), vascular endothelial
      growth factor alpha (VEGFalpha), and insulin-like growth factor-binding protein-5
      (IGFBP5), are abnormally expressed in psoriatic dermal MSCs. As a key regulator
      of gene expression, miRNA are involved in a wide variety of biological processes;
      in fact, several miRNAs have been implicated in the development and progression
      of inflammatory or autoimmune disorders. In this study, we compared the miRNA
      expression profiles of dermal MSCs from patients with psoriasis to those in MSCs
      from normal individuals by microarray, and found that the pro-inflammatory miRNA
      miR-155 was significantly overexpressed in psoriatic MSCs (2.44 fold, P < 0.001).
      Additionally, the expression of miR-155 target gene TAB2 (8.47 +/- 1.55 vs 6.38
      +/- 2.10, P < 0.01,) and the downstream gene iNOS (5.26 +/- 2.58 vs 3.73 +/-
      1.89, P < 0.05) was found to be inhibited in psoriatic dermal MSCs by real-time
      PCR. Therefore, we speculated that the elevation in miR-155 levels may be an
      indicator of, or a key regulatory pathway in, the pathogenesis of psoriasis,
      resulting in functionally impaired dermal MSCs.

PMID- 27706700
TI  - Bioinformatic and expression analysis of the OMT gene family in Pyrus
      bretschneideri cv. Dangshan Su.
AB  - With high nutritional value in its fruits, Dangshan Su pear has been widely
      cultivated in China. The stone cell content in fruits is a key factor affecting
      fruit quality in pear, and the formation of stone cells has been associated with
      lignin biosynthesis. O-Methyltransferase (OMT) is a key enzyme involved in lignin
      metabolism within the phenylpropanoid pathway. Here, we screened 26 OMT genes
      from the Pyrus bretschneideri cv. Dangshan Su genome using the DNATOOLs software.
      To characterize the OMT gene family in pear, gene structure, chromosomal
      localization, and conserved motifs of PbOMTs were analyzed. PbOMTs were divided
      into two categories, type I (designated PbCCOMTs) and type II (designated
      PbCOMTs), indicating the differentiation of function during evolution. Based on
      the analysis of multiple sequence alignment, cis-element prediction, and
      phylogenetic relationships, two candidate genes, PbCCOMT1 and PbCCOMT3, were
      selected for the analysis of temporal and spatial gene expression in pear. The
      promoter regions of both PbCCOMT1 and PbCCOMT3 contain regulatory motifs for
      lignin synthesis. Moreover, the two genes show high similarity and close
      phylogenetic relationships with CCOMTs in other species. Expression analysis
      showed that transcript levels of two PbCCOMTs were positively associated with the
      contents of both stone cells and lignin during the development of pear fruit.
      These results suggest that PbCCOMT1 and PbCCOMT3 are closely associated with
      lignin biosynthesis. These findings will help clarify the function of PbOMTs in
      lignin metabolism and to elucidate the mechanisms underlying stone cell formation
      in pear.

PMID- 27706701
TI  - Analysis of FKBP10, SERPINH1, and SERPINF1 genes in patients with osteogenesis
      imperfecta.
AB  - Osteogenesis imperfecta (OI) is a heterogeneous disorder that causes fragility,
      deformity, and fractures in bones. A large number of genes that are associated
      with the disease have been identified in the last decade; this makes the genetic
      diagnosis of OI more difficult. To improve our knowledge of the genetic mutation
      profile in OI we used single-stranded conformation polymorphism screening and
      automated sequencing to investigate the SERPINH1, FKBP10, and SERPINF1 genes,
      which are related to recessive OI, in 23 unrelated Brazilian patients. Nine rare
      changes and four common polymorphisms were detected. Most changes were benign
      genetic variants. In general, changes in the SERPINH1 and SERPINF1 genes were
      synonymous polymorphisms or missense changes located in non-coding regions. A
      pathogenic change was found in the FKBP10 gene. The characterization of mutations
      related to OI in distinct populations can improve our knowledge of the genetic
      aspects of OI and help us develop molecular strategies for the diagnosis of the
      disease.

PMID- 27706702
TI  - Mixed inheritance in the genetic control of ramulosis (Colletotrichum gossypii
      var. cephalosporioides) resistance in cotton.
AB  - Ramulosis is one of the most aggressive diseases in cotton, and understanding the
      genetic control of its resistance is imperative for selecting superior cotton
      genotypes in breeding programs. This study analyzed the inheritance pattern of
      this resistance using chi-square goodness-of-fit tests to determine the
      phenotypic proportions of the F2 generation, and a mixed inheritance approach to
      jointly model major gene and polygenes effects. F1, F2, Rc1, and Rc2 generations
      were obtained by crossing resistant (BRS Facual, CNPA 2984, or CNPA 2043) and
      susceptible (Delta Opal, CNPA 999, or CNPA 2161) genotypes, and were assessed
      under field conditions with artificial inoculation of the pathogen
      (Colletotrichum gossypii var. cephalosporioides). Genetic control of the trait
      varied among the crossings. For Delta Opal x BRS Facual and CNPA 2161 x BRS
      Facual, phenotypic segregations in the F2 generation did not differ from the
      expected proportions for the hypothesis of duplicate genes (15:1). For Delta Opal
      x CNPA 2043, the segregation did not differ from the expected proportions for
      dominant recessive epistasis (13:3). The hypothesis of genetic control by one
      major gene was supported only for the Delta Opal x CNPA 2043 crossing. Three
      other crossings showed evidence of polygenes in the inheritance of the trait. In
      conclusion, major genes and polygenes are likely involved in the genetic control
      of ramulosis resistance in cotton.

PMID- 27706703
TI  - Analysis of allelic variants of rdxA associated with metronidazole resistance in
      Helicobacter pylori: detection of common genotypes in rdxA by multiplex allele
      specific polymerase chain reaction.
AB  - Resistance to metronidazole (Mtz) in Helicobacter pylori is a major problem
      worldwide, especially in developing countries. Alterations in Mtz nitroreductase
      enzymes, such as oxygen-insensitive NADPH nitroreductase (RdxA) and NADPH flavin
      oxidoreductase (FrxA), are the major contributing factors for this resistance. In
      this study, rdxA and frxA were amplified, sequenced, and analyzed in 34 Mtz
      resistant H. pylori isolates (MIC >= 8 MUg/mL) using multiple allele-specific
      polymerase chain reaction (MAS-PCR); this method was developed to target the most
      common genotypes of rdxA in H. pylori. In this study, the rdxA and frxA genes in
      Mtz-resistant H. pylori strains displayed a large number of point mutations. The
      rdxA and frxA genes of Mtz-resistant clinical isolates showed a higher percentage
      of missense mutations (97.1 and 78.6%, respectively) compared to 26695 reference
      strains; additionally, missense mutations were more common than frameshift (20.6
      and 32.1%) and nonsense mutations (8.8 and 10.7%, respectively) in these genes.
      The most common missense mutations in rdxA were D 59 N (94.1%), T 31 E (88.2%),
      and R 131 K (85.3%). The most common missense mutations in frxA were F 72 S
      (57.1%), G 73 S (57.1%), and C 193 S (53.6%). The developed MAS primers, specific
      to position 175 and 392 of rdxA, successfully amplified the common alleles and
      distinguished the variants. MAS-PCR could be a useful tool for epidemiological
      studies of H. pylori, associated with Mtz resistance. rdxA variants must be
      screened in order to ensure the effectiveness of Mtz-based H. pylori therapies in
      developing countries.

PMID- 27706704
TI  - Chemical and genetic diversity of high-seed-yield sorghum (Sorghum bicolor M.)
      germplasms.
AB  - This study evaluated the chemical and genetic diversity of high-seed-yield
      sorghum germplasms from Korea, the United States, and South Africa. We identified
      significant differences in the chemical contents of whole plants at the heading
      stage in all cultivars, including differences in crude protein, fat, fiber, ash,
      neutral detergent fiber, acid detergent fiber, mineral, and fatty acid contents.
      Our results suggest that Banwoldang is the most appropriate cultivar for roughage
      because of its high protein yield. We identified significant differences in the
      tannin, flavonoid, amylose, mineral, crude fat, fatty acid, and 3
      deoxyanthocyanin contents in the whole grain from all cultivars, but not in the
      mineral or crude fat contents. Tannin levels were generally low. IS645 contained
      the highest levels of flavonoids and linolenic acid compounds, and Moktak had the
      highest amylose and deoxyanthocyanidin content in the grain. To assess genetic
      diversity, we used 10 simple sequence repeat (SSR) primer sets to identify 38
      alleles with 3-8 alleles per locus. Based on phylogenetic analysis of the SSR
      markers, the sorghum cultivars were divided into three major groups. Comparison
      of clusters based on chemical compositions with those based on SSRs showed that
      the groups formed by the three native Korean cultivars clustered similarly in
      molecular dendrograms. Association analysis was conducted for the 10 SSR marker;
      48 chemical and growth traits were present for two marker traits (seed color and
      whole plant fatty acid content) with significant marker-trait associations. These
      markers could be used to select sorghum cultivars for breeding programs.

PMID- 27706705
TI  - Methylation differences and expression profiles of the caprine DIO3 gene.
AB  - DIO3 gene encoding type 3 iodothyronine deiodinase is an imprinted gene, located
      in the DLK1-DIO3 (delta-like 1 homolog-type 3 iodothyronine deiodinase) imprinted
      domain, and is potentially involved in degrading excessive amounts of thyroid
      hormone to protect embryogenesis. However, the underlying regulatory mechanism of
      the imprinted DIO3 gene expression during fetal and neonatal development in goats
      has not been elucidated. In this study, we explored the DNA methylation patterns
      of the caprine DIO3 intragenic CpG island and quantified gene expression level in
      six tissues from Chinese Nanjiang Yellow 3-day old kids. The expression of the
      DIO3 gene was determined using quantitative reverse transcription-polymerase
      chain reactions (qRT-PCRs), while the identification of methylation patterns was
      determined using bisulfite-sequencing PCRs. Modest, and non-significant (P >
      0.05), methylation patterns were noted for the DIO3 CpG island methylation in the
      brain, heart, liver, kidney, lung, and longissimus dorsi tissues (ranging from
      26.48 to 34.92%). The expression level of the DIO3 mRNA was significantly higher
      (P < 0.05) in the liver tissue than in the other five tissues. Pearson's
      correlation analysis revealed that there was no significant relationship between
      methylation and gene expression (P > 0.05), which indicated that the expression
      of the caprine DIO3 gene was likely modified by other regulatory elements. This
      study identified DNA methylation and expression patterns of the DIO3 gene in
      goats and provided insights into further regulatory mechanisms of expression and
      imprinting in the DLK1-DIO3 domain.

PMID- 27706706
TI  - Genetic diversity analysis of Varronia curassavica Jacq. accessions using ISSR
      markers.
AB  - Varronia curassavica Jacq. is a medicinal and aromatic plant from Brazil with
      significant economic importance. Studies on genetic diversity in active germplasm
      banks (AGB) are essential for conservation and breeding programs. The aim of this
      study was to analyze the genetic diversity of V. curassavica accessions of the
      AGB of Medicinal and Aromatic Plants of the Federal University of Sergipe (UFS),
      using inter-simple sequence repeat molecular markers. Twenty-four primers were
      tested, and 14 were polymorphic and informative, resulting in 149 bands with
      97.98% polymorphism. The UPGMA dendrogram divided the accessions into Clusters I
      and II. Jaccard similarity coefficients for pair-wise comparisons of accessions
      ranged between 0.24 and 0.78. The pairs of accessions VCUR-001/VCUR-503, VCUR
      001/VCUR-504, and VCUR-104/VCUR-501 showed relatively low similarity (0.24), and
      the pair of accessions VCUR-402/VCUR- 403 showed medium similarity (0.78). Twenty
      eight accessions were divided into three distinct clusters, according to the
      STRUCTURE analysis. The genetic diversity of V. curassavica in the AGB of UFS is
      low to medium, and it requires expansion. Accession VCUR-802 is the most suitable
      for selection in breeding program of this species, since it clearly represents
      all of the diversity present in the AGB.

PMID- 27706707
TI  - Diagnosis and epidemiology of canine leishmaniasis in southeastern Bahia, Brazil.
AB  - Leishmaniasis is a disease caused by protozoa of the genus Leishmania. Two
      distinct forms are recognized: visceral leishmaniasis (VL) and cutaneous
      leishmaniasis (CL). In the Americas, the causative agent of VL is L. infantum
      chagasi, whereas L. braziliensis is principally responsible for CL. Domestic dogs
      constitute the main source of VL in urban environments, and have also been
      implicated in CL epidemiology. We carried out molecular and serological surveys
      to detect Leishmania infection in dogs from the municipality of Itubera in Bahia,
      Brazil. Furthermore, we identified risk factors associated with illness in dogs
      from this locality. Blood samples were collected from 399 dogs and tested using
      an indirect immunofluorescence assay (IFA) and polymerase chain reaction (PCR) to
      detect Leishmania spp antibodies and L. infantum chagasi and L. braziliensis DNA,
      respectively. Dogs were clinically evaluated and tissue samples from those
      exhibiting skin lesions were examined for parasites. In addition, the dog owners
      completed an epidemiological questionnaire to identify factors associated with
      infection. Skin lesions consistent with CL were found on 37 (9.3%) of the
      evaluated animals, but parasitological examination was negative for all samples.
      The IFA returned positive results for 60 (15%) dogs. PCR identified DNA from L.
      braziliensis in 86 (21.6%) animals, where as all samples proved negative for L.
      infantum chagasi. The 134 dogs (33.6%) testing positive using IFA and/ or PCR
      were considered infected, and of these, only 13 demonstrated skin lesions.
      Animals from rural areas were 3.39-times more likely to be infected compared to
      those in urban environments.

PMID- 27706708
TI  - Characterization of a novel Cry8Ea3-binding V-ATPase Subunit A in Holotrichia
      parallela.
AB  - Several receptor proteins of Cry toxin have been previously identified, including
      cadherin-like, aminopeptidase N, and alkaline phosphatase. In the present work, a
      novel binding protein, V-ATPase subunit A (HpVAA), was identified in Holotricia
      parallela larvae and characterized. We performed reverse transcription-polymerase
      chain reaction and rapid amplification of cDNA ends technology to obtain the cDNA
      of the full-length hpvaa. Sequencing analysis showed that the open reading frame
      of hpvaa (GenBank accession No. KU497557) is 1845 bp long, encoding 614 amino
      acid residues. The predicted molecular weight and isoelectric point of HpVAA were
      67.85 kDa and 4.9, respectively. The HpVAA protein, which includes two putative
      conserved domains, ATP-synt_ab_N and ATP-synt_ab_C, and a Walker A (GAFGCGKT)
      motif and a Walker B (SMMAD) motif, possesses the same structural characteristics
      as V-ATPase subunit A from other insects. The protein was successfully expressed
      in Escherichia coli, and a ligand blot assay showed binding of the protein with
      Cry8Ea3 toxin. Transcriptional analysis of hpvaa in different tissues of H.
      parallela larvae was performed by qRT-PCR, which showed that the relative
      expression of hpvaa in the Malpighian tubules is higher than that in other
      tissues.

PMID- 27706709
TI  - Growth factor progranulin blocks tumor necrosis factor-alpha-mediated inhibition
      of osteoblast differentiation.
AB  - Tumor necrosis factor-alpha (TNF-alpha) stimulates osteoclast differentiation and
      suppresses osteoblast differentiation, leading to bone loss and decreased bone
      mass in local inflammation areas in patients with rheumatoid arthritis. The
      growth factor progranulin (PGRN) is expressed in various types of cells and play
      crucial roles in the pathogenesis of atherosclerosis and arthritis by blocking
      TNF-alpha. Here, we investigated the role of PGRN in blocking TNF-alpha-mediated
      inhibition of osteoblast differentiation and the regulatory mechanism. C2C12 stem
      cell was induced by bone morphogenetic protein-2 (BMP-2) for osteoblast
      differentiation. A significant increase in ALP activity (P < 0.001), as well as
      the expression of ColI, Ocn, and Bsp in the induced cells (P < 0.01 and P <
      0.001) were observed; the marker gene expression and ALP activity were inhibited
      by TNF-alpha (P < 0.01 and P < 0.001). PGRN significantly blocks the TNF-alpha
      mediated inhibition of osteoblast differentiation, evidenced by the ALP activity
      (P < 0.05 and P < 0.01), Alizarin red staining, the expression of ColI, Ocn, and
      Bsp (P < 0.05 and P < 0.01) and the osteoblast key transcription factor gene
      Runx2 (P < 0.01), Osx (P < 0.05), and ATF4 (P < 0.05). Mechanical study indicated
      that PGRN significantly blocks the TNF-alpha-mediated stimulation of NF-kB
      signaling (P < 0.01 and P < 0.001). PGRN exerts a protective effect on osteoblast
      differentiation in an inflammatory environment. Thus, we concluded that the
      treatment of osteoblasts with PGRN could be used in the future to prevent or
      treat rheumatoid arthritis-associated bone loss.

PMID- 27706710
TI  - Investigating the association between XRCC1 gene polymorphisms and susceptibility
      to gastric cancer.
AB  - We carried out a hospital-based case-control study to investigate the role of
      XRCC1 gene Arg399Gln, Arg280His, and Arg194Trp polymorphisms in susceptibility to
      gastric cancer. A total of 214 gastric cancer patients and 247 control subjects
      were recruited between March 2013 and March 2015, and polymorphism genotype
      frequencies were determined by polymerase chain reaction-restriction fragment
      length polymorphism. Using the chi-square test, we detected statistically
      significant differences in age (chi-square = 22.25, P < 0.001), gender (chi
      square = 6.74, P = 0.01), and family history of cancer (chi-square = 4.73, P =
      0.03) between the case and control groups. Logistic regression analysis revealed
      that the XRCC1 Arg194Trp TT genotype conferred increased susceptibility to
      gastric cancer compared to the CC genotype [odds ratio (OR) = 2.38, 95%
      confidence interval (CI) = 1.28-4.49]. Moreover, individuals carrying the T
      allele of this variant were found to be at moderately increased risk of this
      disease (OR = 1.56, 95%CI = 1.16-2.09). However, the XRCC1 Arg399Gln and
      Arg280His polymorphisms were shown to have no influence on the development of
      gastric cancer. In conclusion, we suggest that the XRCC1 gene Arg194Trp
      polymorphism is associated with gastric cancer susceptibility in the Chinese
      population.

PMID- 27706711
TI  - Comparative analysis of short tandem repeat data obtained by automated and gel
      electrophoresis techniques.
AB  - Short tandem repeats (STRs) are commonly used as genetic markers. The detection
      and analysis of STRs can be used to gather information on polymorphisms of
      interest to forensic geneticists. Denaturing polyacrylamide gel electrophoresis
      (PAGE) is an affordable method for the detection of minor sequence changes in
      DNA, while capillary electrophoresis (CE) is the gold standard for genotyping
      analysis. This appears to be the first study to directly compare data obtained
      using the two electrophoretic techniques. We analyzed genomic DNA from 209
      individuals to compare genotyping results from seven Combined DNA Index System
      (CODIS) STR markers obtained by both techniques. The automated electrophoresis
      was carried out using a MegaBACETM 1000 DNA analysis system. Full concordance was
      found in 1297 of 1308 STR allele calls. Kappa and McNemar-Bowker tests indicated
      that there were no statistically significant differences between the results from
      the two methods. There was no statistically significant difference in precision
      between denaturing PAGE followed by silver nitrate staining, despite a longer
      protocol, compared with CE when applied to population studies. STR allele
      frequency data from non-automated genotyping techniques seem to be just as
      reliable as from automated genotyping methods.

PMID- 27706712
TI  - Contributions of polymorphisms in miR146a, miR196a, and miR499 to the development
      of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is one of the most common malignant tumors worldwide; it
      is estimated that there were 782,000 new cases in 2012. MicroRNAs (miRNAs) play
      an important role in carcinogenesis by regulating oncogenes and tumor
      suppressors. We investigated the role of miR-146a, miR-196a2, and miR-499
      polymorphisms in the risk of hepatocellular carcinoma in a Chinese population.
      Hepatocellular carcinoma patients (175) and healthy controls (302) were recruited
      between April 2013 and March 2015. Genotype analysis of miR-146a, miR-196a2, and
      miR-499 polymorphisms was carried out by polymerase chain reaction-restriction
      fragment length polymorphism. There was a significant difference between the
      genotype distribution of miR-196a2 in hepatocellular carcinoma patients and
      controls (X2 = 17.23, P < 0.001). CG and GG miR-146a genotypes significantly
      elevated the risk of hepatocellular carcinoma compared with the CC genotype, with
      adjusted ORs (95%CI) of 3.05 (1.07-8.70) and 4.96 (1.64-14.97), respectively. In
      the recessive model, the CG + GG genotype had a 3.75-fold risk of hepatocellular
      carcinoma compared with the CC genotype, with an adjusted OR (95%CI) of 3.75
      (1.39-10.11). However, no significant association was observed between miR-196a2
      and miR-499 variants and risk of hepatocellular carcinoma in the co-dominant,
      dominant, and recessive models. The miR-146a polymorphism is a G to C
      substitution that causes a mismatch in the stem-loop of miRNA, which influences
      how the expression and transcriptional regulation of miRNA affects its target
      genes. Our study revealed that the GG and CG genotypes of miR-146a increased the
      risk of hepatocellular carcinoma in the Chinese population.

PMID- 27706713
TI  - Genetic diversity of the forage peanut in the Jequitinhonha, Sao Francisco, and
      Parana River valleys of Brazil.
AB  - Arachis pintoi and A. repens are legumes with a high forage value that are used
      to feed ruminants in consortium systems. Not only do they increase the
      persistence and quality of pastures, they are also used for ornamental and green
      cover. The objective of this study was to analyze microsatellite markers in order
      to access the genetic diversity of 65 forage peanut germplasm accessions in the
      section Caulorrhizae of the genus Arachis in the Jequitinhonha, Sao Francisco and
      Parana River valleys of Brazil. Fifty-seven accessions of A. pintoi and eight of
      A. repens were analyzed using 17 microsatellites, and the observed heterozygosity
      (HO), expected heterozygosity (HE), number of alleles per locus, discriminatory
      power, and polymorphism information content were all estimated. Ten loci (58.8%)
      were polymorphic, and 125 alleles were found in total. The HE ranged from 0.30 to
      0.94, and HO values ranged from 0.03 to 0.88. By using Bayesian analysis, the
      accessions were genetically differentiated into three gene pools. Neither the
      unweighted pair group method with arithmetic mean nor a neighbor-joining analysis
      clustered samples into species, origin, or collection area. These results reveal
      a very weak genetic structure that does not form defined clusters, and that there
      is a high degree of similarity between the two species.

PMID- 27706714
TI  - Correlation between serum level of chemokine (C-C motif) ligand 18 and poor
      prognosis in breast cancer.
AB  - In this study, we investigated the correlation between serum chemokine (C-C
      motif) ligand 18 (CCL-18) and the prognosis as well as clinical characteristics
      of breast cancer. Blood samples from 207 breast cancer patients, 126 individuals
      with benign breast tumors, and 93 healthy women were collected. Serum CCL-18
      expression was detected by enzyme-linked immunosorbent assay. Mann-Whitney's U
      tests were carried out to analyze the relationship between serum CCL-18 and
      clinicopathological variables. The Kaplan-Meier method was used to evaluate the
      overall survival (OS), whereas differences between groups were analyzed by log
      rank tests. The COX proportional hazard regression model was used to determine
      the association between clinicopathological characteristics and survival. We
      found that serum CCL-18 was significantly higher in breast cancer patients
      (290.06 +/- 89.52 pg/mL) as compared to that in individuals with benign tumors
      (170.14 +/- 26.57 pg/mL) or healthy women (119.36 +/- 38.77 pg/mL) (P < 0.05).
      Serum CCL-18 was correlated with clinical cancer stages (P = 0.007), and was
      associated with advanced cancer stage (P < 0.05). The 5-year OS rate of breast
      cancer patients with high serum CCL- 18 was 35.9% (HR = 3.908, 95%CI = 2.546
      12.090, P < 0.05), which was significantly lower as compared to that for patients
      with low serum CCL-18 (85.5%). Based on our results, we conclude that CCL-18 is a
      prognostic biomarker in patients with advanced breast cancer in Chinese patients.

PMID- 27706715
TI  - Effects of MMP-1 and MMP-3 gene polymorphisms on gene expression and protein
      level in lumbar disc herniation.
AB  - The aim of this study was to identify the possible correlation between
      polymorphisms in matrix metalloproteinase (MMP)-1 and MMP-3 and their
      corresponding protein levels in disc tissues obtained from patients with lumbar
      disc herniation (LDH) using biochemical and immunohistochemical analyses. Blood
      and disc samples were obtained from 100 patients with LDH who underwent a lumbar
      microdiscectomy. Based on the radiological degeneration, the patients were
      diagnosed with grade 2, 3, or 4 LDH. MMP-1 -1607 1G/2G and MMP-3 -1171 5A/6A were
      analyzed by real-time polymerase chain reaction. The expressions of MMP-1 and MMP
      3 were detected by biochemical and immunohistochemical analyses. We found no
      association between the MMP-1 polymorphism and disc degeneration and MMP-1
      expression. However, patients expressing the 6A/6A and 5A/6A alleles of MMP-3 
      11715A/6A showed higher MMP-3 expression, compared to those expressing the 5A/5A
      genotype. Additionally, the radiological degeneration grades were correlated with
      the histological degeneration scoring. Protein levels and immunopositive cell
      rates of MMP-1 and MMP-3 were associated with disc degeneration grades. Moreover,
      the MMP-1 and MMP-3 expression and the histological and radiological scores were
      positively correlated and the MMP-3 -11715A/6A polymorphism was associated with
      MMP-3 expression in herniated disc tissues. This study is the first to
      investigate polymorphisms in MMP-1 and MMP-3, as well as their corresponding
      protein expressions. We also quantified an association between the radiological
      degeneration grades and MMP-1 and MMP- 3 expression. Further genomic studies on
      MMPs could focus on the utilization of MMP-1 and MMP-3 as markers for the
      prevention and treatment of this disease.

PMID- 27706716
TI  - Expression patterns of two heat-shock cognate 70 genes during immune responses
      and larval development of the Chinese mitten crab Eriocheir sinensis.
AB  - Two heat-shock protein (HSP) 70 family transcripts, heat-shock protein 70 cognate
      5 and heat-shock protein 70 cognate 3 (designated as EsHSC70-5 and EsHSC70-3,
      respectively), were isolated from the Chinese mitten crab Eriocheir sinensis and
      their expression profiles were evaluated for their responsiveness to larval
      development and immune challenge in adult crabs. The HSPs exhibited 45-89%
      identity with other heat-shock proteins, and they shared similar structural
      features. EsHSC70 mRNA expression was detected not only during infection but also
      during the developmental larval stages. The EsHSC70s were enriched, and their
      expression fluctuated during early development. EsHSC70 mRNA expression was
      significantly induced by Vibrio parahaemolyticus challenge in all of the tissues
      studied (P < 0.05). Expression of EsHSC70 mRNA in the hepatopancreas and at the
      early zoeal stages was particularly pronounced, and the two EsHSC70s exhibited
      differential expression patterns both chronologically and spatially. The EsHSC70
      5 mRNA level was significantly downregulated in the intestine and gills compared
      to that in controls at nearly all time points, and was expressed at a lower level
      after the bacterial challenge, indicating that EsHSC70-5 and EsHSC70-3 respond to
      immune challenges. The stage-specific enrichment of EsHSC70 transcripts in crabs
      suggests that these stress proteins play an essential role during brachyurization
      events.

PMID- 27706717
TI  - HPV genotyping and p16 expression in Xingu Indigenous Park, Brazil.
AB  - The association between high-risk human papillomavirus (HPV) genotypes and p16
      expression in indigenous women from the Xingu Indigenous Park, Brazil, was
      unknown. This study evaluated p16 expression in women with a histological
      diagnosis of cervical intraepithelial neoplasia (CIN) 3 or higher and correlated
      this expression with HPV genotypes to determine possible discrepancies in the
      expression of this marker. We evaluated 37 previously collected samples with
      different HPV genotypes and high-grade lesions diagnosed based on cytology,
      histology, and colposcopy. Immunohistochemical analysis was performed using
      paraffin-embedded tissue sections and the CINtec(r) Histology Kit. p16 protein
      expression was investigated by immunostaining with an anti-p16 antibody. HPV
      genotyping was performed by reverse hybridization. The age of the study
      population ranged from 22-75 years (43.81 +/- 15.89 years) and parity ranged from
      1-11 (5.92 +/- 2.58). Thirteen different HPV genotypes were found using the INNO
      LiPA kit. Single and multiple infections by HPV were found with prevalence of
      single infections (P = 0.029). Comparison between HPV genotype and simple or
      multiple infections was highly significant; it was observed more HPV 52 followed
      by HPV 16 in single infections (P < 0.001). p16 expression was predominantly
      diffuse, which was observed in 91.7% of lesions, whereas 8.3% were focal (P <
      0.001). HPV 52, HPV 16 and 31 were the most prevalent HPV types in high-grade CIN
      in these indigenous women. Diffuse p16 expression in high-grade CIN was not
      influenced by the viral genotype; however, more studies are necessary to further
      our understanding of this restricted group.

PMID- 27706718
TI  - Changes in methylation of genomic DNA from chicken immune organs in response to
      H5N1 influenza virus infection.
AB  - DNA methylation is an important epigenetic modification in eukaryotes, which
      plays a significant role in regulating gene expression. When the host is invaded
      by the influenza virus, gene expression is regulated via changes in DNA
      methylation levels or patterns, leading to the activation or suppression of
      relevant signaling pathways or networks, triggering a series of immune responses
      against viral invasion. Here, we investigated the changes in genomic DNA
      methylation in the immune organs of chicken infected with H5N1 influenza virus.
      Genome-wide DNA methylation levels in the spleen, thymus, and bursa of Fabricius
      of specific pathogen-free (SPF) chicken infected with the Guangdong (G-H5N1) and
      Anhui (A-H5N1) H5N1 strains, and water (control) were analyzed by fluorescence
      labeled methylation-sensitive amplified polymorphism (F-MSAP). The results
      indicated that total DNA methylation levels did not differ between spleen genomic
      DNA in chicken treated with different viral strains and the control (P > 0.05).
      However, the total DNA methylation levels were significantly upregulated in the
      thymus (P < 0.01) and bursa (P < 0.05) of chicken in the A-H5N1 group compared to
      those in the G-H5N1 and control groups. These results provide a basis for the
      screening of avian influenza-resistance genes or methylation markers, analyzing
      the epigenetic regulation mechanisms of avian influenza, and performing selective
      breeding for disease resistance.

PMID- 27706719
TI  - Interleukin-6 -572G/C polymorphism and prostate cancer susceptibility.
AB  - Strong evidence suggests that cancer-associated inflammation promotes tumor
      growth and progression, and interleukin-6 (IL6) is an important modulator of
      inflammation. However, the roles of IL6 and mutations of its corresponding gene
      in prostate cancer have not been clearly documented. We retrieved data from the
      Oncomine database concerning IL6 expression in prostate cancer and its role in
      prostate-specific antigen (PSA) recurrence. We also performed a case-control
      study of the IL6 -572G/C polymorphism (rs1800796) in 236 sporadic prostate cancer
      patients and 256 healthy controls from a southern Han Chinese population. Odds
      ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the
      association between rs1800796 and prostate cancer susceptibility. A dual
      luciferase reporter assay was used to test the transcriptional activity of the
      IL6 promoter G and C alleles. IL6 was overexpressed in prostate cancer tissues
      compared to normal tissues, especially in those with higher Gleason scores.
      Moreover, elevated IL6 expression was associated with high PSA recurrence rate in
      Oncomine data. Our case-control study demonstrated that compared with the -572C
      allele, the -572G allele conferred a borderline increased risk of prostate cancer
      (OR = 1.31, 95%CI = 0.99-1.74, P = 0.061). This was more pronounced in the
      subgroup of individuals having never smoked (OR = 1.85, 95%CI = 1.07-3.22).
      Moreover, the G allele showed increased activity relative to the C allele in the
      dual-luciferase reporter assay. Our results suggest that the -572G/C polymorphism
      may be associated with IL6 expression, which in turn plays a role in prostate
      cancer development.

PMID- 27706720
TI  - Phylogenetic analysis of the Mongolian gerbil (Meriones unguiculatus) from China
      based on mitochondrial genome.
AB  - Meriones unguiculatus (Gerbillinae, Rodentia) is widely used as an animal model
      of human disease. Here, we provide the first report of the complete mitochondrial
      genome sequence of M. unguiculatus (GenBank accession Nos. KF425526 and
      NC_023263). The sequence contained the conserved vertebrate pattern of 13 protein
      coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and 1 major noncoding region.
      We identified one extended termination-associated sequence and one conserved
      sequence block in the non-coding region. The putative origin of replication for
      the light strand (OL) was 35 bp long. The OL stem and adjacent sequences were
      highly conserved, but the loop region differed from those of other rodent
      species. Base composition and codon usage of the 13 protein-coding genes in M.
      unguiculatus were compared with those of 23 rodent species with previously
      sequenced mitochondrial genomes. An A+T content of 63.0% was present in M.
      unguiculatus; this is similar to the Murinae average (62.4 +/- 0.8%) and falls
      between the average for Mus musculus (63.1 +/- 0.1%) and Rattus sp (61.7 +/-
      0.4%). The AT and GC skew values of M. unguiculatus were 0.035 and -0.28,
      respectively, similar to those of Cricetinae species (0.057 +/- 0.05 and -0.31 +/
      0.05). The codon families exhibited similar abundance in all 24 species.
      Analysis of phylogenetic relationships with 23 other rodent species using
      neighbor-joining and maximum likelihood protocols and the 12 protein-coding
      regions on the H strand showed that M. unguiculatus should be classified as genus
      Meriones, sub-family Gerbillinae, family Muridae.

PMID- 27706721
TI  - Correlation between polymorphisms in the estrogen receptor alpha gene and
      coronary heart disease: A meta-analysis.
AB  - The aim of this study was to conduct a systematic evaluation the correlation
      between polymorphisms in the estrogen receptor alpha gene (ESRalpha) and coronary
      heart disease susceptibility. Case-control studies until August 2015 analyzing
      the correlation between the ESRalpha PvuII T/C polymorphism and coronary heart
      disease were obtained from various electronic databases (CBM, CNKI, Wanfang Data,
      VIP, and MEDLINE, Cochrane Library, Embase, Springer, and Ovid. The data obtained
      from these studies were evaluated and valid data was extracted. A meta-analysis
      was performed using RevMan 5.0. Eleven cases, comprising 1742 patients with
      coronary heart disease and 2012 controls, that conformed to the inclusion
      criteria set in this study were extracted. The results of our meta-analysis
      indicated that the C and T alleles, the TC+CC and TT genotypes, and the CC and
      TT+TC genotypes did not differ significantly. The results of this meta-analysis
      confirmed that there was no correlation between polymorphisms in ESRalpha and
      coronary heart disease susceptibility in the Chinese population.

PMID- 27706722
TI  - Bone morphogenetic protein 9 facilitates osteocarcinoma cell apoptosis and
      inhibits in vivo tumor growth.
AB  - Osteosarcoma (OS) causes millions of death worldwide and, since there is no
      effective therapy, it is necessary to identify the molecular mechanism of OS,
      which can direct the development of new therapies. This study investigated the
      role of bone morphogenetic protein 9 (BMP9), a member of the transforming growth
      factor (TGF)-beta family, in OS development. This study first examined BMP9
      expression in tissue from OS patients and normal subjects. The OS cell line
      (MG63) and tumor cells from OS patients were then transfected with BMP9 and cell
      proliferation and apoptosis were assessed. Western blot and reverse transcription
      polymerase chain reaction were used to study the expression of cancer-related
      genes [B cell lymphoma (Bcl)-2, cleaved Caspase-3, Caspase-9, and poly ADP-ribose
      polymerase]. To confirm the in vivo impact of BMP9, mice were transplanted with
      OS tumor cells and then treated with BMP9 carried in attenuated Salmonella
      enterica serovar Typhimurium. Our study found that the OS tumor tissue had a
      lower expression of BMP9 compared to normal tissue. Transfection of BMP9 in OS
      and MG63 cells inhibited cell growth and promoted apoptosis. In vitro studies
      showed a decrease in Bcl-2 gene expression and an increase in Cyto-c, Caspase-3,
      and Caspase-9 expression. In vivo studies indicated that consistent treatment
      with BMP9 in OS mice results in inhibition of tumor growth. This study shows that
      BMP9 inhibition is associated with OS development and that enhanced expression of
      BMP9 may be a potential treatment method for OS.

PMID- 27706723
TI  - Association between functional polymorphisms in the nitric oxide synthase 3 gene
      and pediatric acute respiratory distress syndrome.
AB  - Nitric oxide mediates multiple physiological functions, including
      neurotransmission, immune regulation, angiogenesis, antiplatelet activity, and
      surfactant maturation or secretion. Mice deficient in the nitric oxide synthase 3
      (NOS3) gene displayed defective lung vascular development and fatal respiratory
      distress. Polymorphisms in NOS3 have been reported to be associated with
      respiratory distress syndrome (RDS). The role of NOS3 polymorphisms as a risk
      factor for pediatric acute respiratory distress syndrome (PARDS) was evaluated by
      analyzing the possible functional single nucleotide polymorphisms (SNPs) in the
      regulatory and coding regions of NOS3. Samples from 216 PARDS patients and 225
      healthy control subjects were genotyped at 4 SNP loci (rs11771443 and rs3918188
      in the promoter region, rs1799983 in exon 7, and rs7830 at the intron24-exon23
      boundary). Statistically significant differences were observed in the allelic or
      genotypic frequencies of the rs1799983 and rs11771443 polymorphisms in NOS3. The
      T and G alleles of rs1799983 and rs11771443 were associated with a significantly
      higher risk of PARDS compared to the C allele (P = 0.030) and the T allele (P =
      0.004), respectively. Strong linkage disequilibrium was observed in one block (D'
      > 0.9). Subjects with PARDS displayed significantly fewer T-C haplotypes (P =
      0.013) in block 1 (rs1799983-rs11771443). These findings indicate that NOS3
      polymorphisms play a definitive role in PARDS, and therefore may be useful for
      future genetic or neurobiological studies on RDS.

PMID- 27706725
TI  - Effect of pregnane X receptor polymorphisms on tacrolimus blood concentrations
      and the resulting adverse reactions in kidney transplantation recipients.
AB  - We investigated the effect of pregnane X receptor (PXR) polymorphisms on
      tacrolimus (FK506) blood trough concentrations and the associated adverse
      reactions in kidney transplantation recipients (KTRs). Polymerase chain reaction
      (PCR)-restriction fragment length polymorphism was used to detect the genotypes
      of single nucleotide polymorphism loci in 336 KTRs. The PXR six-base deletion
      mutation was classified using specific allele PCR, and the FK506 blood trough
      concentration in the KTRs was measured by chemiluminescent microparticle
      immunoassay. There were significant differences in adverse reactions resulting
      from FK506 in age, weight, body mass index (BMI) and treatment course (P < 0.05).
      Logistical regression revealed that the FK506 treatment course and BMI were risk
      factors for hyperlipidemia, and the risk of hyperlipidemia increased 27.534 times
      when the BMI was less than 18.5. Moreover, age was also a risk factor leading to
      hyperglycemia. FK506 blood trough concentration and C0/D value had an impact on
      adverse reactions induced by hyperglycemia. The KTRs' PXR rs3842689, rs6785049,
      and rs1523127 mutation frequencies were 26.07, 11.79, and 16.07%, respectively.
      There was no statistically significant difference in the mutation frequency of
      each locus between the control group and the adverse reaction groups. Therefore,
      rs3842689, 7635G>A (rs6785049), and 24381C>A (rs1523127) PXR polymorphisms have
      no obvious impact on FK506; furthermore, the PXR rs3842689 wild-type homozygous
      WW genotype is a risk factor of FK506 and results in gastrointestinal reactions.

PMID- 27706724
TI  - Clinical study of the correlation between complement factor H polymorphism and
      age-related macular degeneration.
AB  - This study aimed to investigate the correlation between age-related macular
      degeneration (AMD) of the liver-kidney yin-deficiency type and complement factor
      H (CFH) polymorphism, and to determine whether the C allele of the T1277C (Y402H)
      variant is a risk factor for this condition. We performed a case-control
      investigation of 60 patients with liver-kidney yin-deficiency AMD and 60 normal
      control subjects. Peripheral blood was collected from each participant for DNA
      extraction. Following amplification by polymerase chain reaction, the DNA samples
      were sequenced, and polymorphism of the CFH gene was examined. Data were analyzed
      with the chi-square test, with P < 0.05 signifying statistical significance. The
      frequency of the C allele was significantly higher in the wet than in the dry AMD
      group (P = 0.044). In addition, the TC and CC genotypes were markedly more common
      in the former than in the control group (P = 0.013), and there was a significant
      difference in the distribution of the T and C alleles between wet AMD patients
      and control subjects (P < 0.05). Based on this, we conclude that liver-kidney yin
      deficiency AMD is associated with the C allele and TC and CC genotypes of the CFH
      Y402H polymorphism. Among patients with this condition, CFH genotypes were
      normally distributed. The principal CFH genotypes that induce liver-kidney yin
      deficiency AMD are the mutant homozygote CC and heterozygote TC forms. Moreover,
      C allele carriers are at higher risk of developing this disease.

PMID- 27706726
TI  - Isolation and characterization of microsatellite loci in Sisyrinchium (Iridaceae)
      and cross amplification in other genera.
AB  - Recent phylogenetic studies on Sisyrinchium strongly suggest that species
      classified in section Hydastylus and section Viperella belong to a single group
      of plants in recent adaptive radiation (Clade IV). These species neither present
      clear morphological differentiation among them nor show clear identification
      using DNA barcode markers. Thus, the main goal of this study was to develop a set
      of polymorphic microsatellite markers compatible for representative species of
      both sections to ensure variability that could be revealed by SSR markers.
      Therefore, microsatellite primers were isolated and characterized for
      Sisyrinchium palmifolium and S. marchioides. In addition, transferability of the
      developed primers was tested in Iridoideae, primarily in closely related species
      of Sisyrinchium. Sixteen microsatellite loci were developed from enriched genomic
      libraries, of which ten were polymorphic. GST values indicated higher
      differentiation among subpopulations of S. palmifolium than those from S.
      marchioides. Major transferability was obtained using primers isolated from S.
      marchioides. All primers exhibited higher rates of cross-amplification for
      species belonging to Clade IV of Sisyrinchium, as well as to the genera Calydorea
      and Herbertia. These developed microsatellite markers can be used as an efficient
      tool for characterization of genetic variability in species belonging to
      Iridoideae, as well as for studies on population dynamics, genetic structure, and
      mating system in other Sisyrinchium species.

PMID- 27706727
TI  - A glimpse of the endophytic bacterial diversity in roots of blackberry plants
      (Rubus fruticosus).
AB  - The aim of this study was to explore the diversity of culturable bacterial
      communities residing in blackberry plants (Rubus fruticosus). Bacterial
      endophytes were isolated from plant roots, and their 16S rDNA sequences were
      amplified and sequenced. Our results show that the roots of R. fruticosus exhibit
      low colony forming units of bacterial endophytes per gram of fresh tissue (6 x
      102 +/- 0.5 x 102). We identified 41 endophytic bacterial species in R.
      fruticosus by BLAST homology search and a subsequent phylogenetic analysis,
      belonging to the classes Actinobacteria, Bacilli, Alfaproteobacteria,
      Betaproteobacteria, and Gammaproteobacteria. Predominantly, genera belonging the
      Proteobacteria (Burkholderia, 29.4%; Herbaspirillum, 10.7%; Pseudomonas, 4.9%;
      and Dyella, 3.9%), Firmicutes (Bacillus, 42.1%), and Actinobacteria (two isolates
      showing high identity with the Streptomyces genus, 1.9%) divisions were
      identified. Fifty percent of the bacterial endophytes produced the phytohormone
      indole-acetic acid (IAA), eleven of which exhibited higher IAA production (>5.8
      mg/mL) compared to the plant growth-promoting strain, Pseudomonas fluorescens
      UM270. Additionally, the endophytic isolates exhibited protease activity (22%),
      produced siderophores (26.4%), and demonstrated antagonistic action (>50%
      inhibition of mycelial growth) against the grey mold phytopathogen Botrytis
      cinerea (3.9%). These results suggested that field-grown R. fruticosus plants
      contain bacterial endophytes within their tissues with the potential to promote
      plant growth and display antagonism towards plant pathogens.

PMID- 27706728
TI  - Associations of serotonin receptor gene HTR3A, HTR3B, and HTR3A haplotypes with
      bipolar disorder in Chinese patients.
AB  - Single nucleotide polymorphisms (SNPs) in HTR3A and HTR3B have been reported to
      be associated with bipolar disorder in European and Japanese populations. We
      explored the roles of 21 tag SNPs in HTR3A and HTR3B in susceptibility to bipolar
      disorder in a Chinese cohort. Twenty-one Tag SNPs were genotyped in a study
      consisting of 130 patients with bipolar disorder, who visited Shandong Mental
      Health Center between June 2013 and May 2014, and 109 healthy individuals as
      controls. All of the tag SNPs were genotyped using Sequenom MassArray matrix
      assisted laser desorption/ionization time of flight spectrometry. Plink 1.07,
      Haploview 4.2, and SPSS 20.0 were used for the analysis of the genotypes and the
      associations of the haplotypes with bipolar disorder. Association analyses of tag
      SNPs detected significant associations with the A allele in HTR3A rs1176719 (P =
      0.030) and the C allele in HTR3A rs1176713 (P = 0.048). Haplotype-based
      association analyses indicated a statistically significant (P = 0.035) five-SNP
      haplotype (rs1062613:C, rs11604247:C, rs1176722:G, rs2276302:A, rs1176719:G) of
      linkage disequilibrium in block 3. Analysis of our small Chinese sample revealed
      a significant association of HTR3A with bipolar disorder, but yielded no evidence
      of an association between HTR3B and bipolar disorder. Furthermore, evidence for
      an association was found for a haplotype of HTR3A. Studies with larger Chinese
      samples are needed to verify our findings.

PMID- 27706729
TI  - Combining abilities for agronomic traits and marker-assisted selection for Potato
      virus X and Potato virus Y resistance.
AB  - Disease-resistant potato cultivars with good tuber appearance and desirable
      agronomic traits are essential for meeting the demands of producers and the
      market. Attaining these cultivars is the focus of potato breeding programs whose
      aim is to benefit the productive chain. The purpose of this study was to estimate
      combining abilities and evaluate potato clones based on tuber appearance, yield,
      and resistance to the PVY and PVX viruses. Crosses between four commercial
      cultivars of potato with good tuber appearance were performed, using eight clones
      with proven resistance to PVY and PVX from the breeding program of UFLA. The
      clones obtained were evaluated for agronomic traits, tuber appearance, and the
      presence of both Ryadg and Rx1 alleles, which confer extreme resistance to the
      PVY and PVX viruses, respectively. The independent culling level method was used
      to select genotypes of commercial interest, as well as to estimate the combining
      abilities of the parents. We identified clones carrying the Ryadg and Rx1 alleles
      with agronomic traits suitable for the fresh market and for processing. The BRS
      Ana cultivar and CMA-399 and CMA-385 clones showed positive effects on general
      combining ability (GCA) for tuber yield, while the Monalisa cultivar showed
      positive effects on GCA for general tuber appearance.

PMID- 27706730
TI  - Cytogenetic evaluation of cataract patients occupationally exposed to ionizing
      radiation in northeast China.
AB  - Long-term radiation exposure is hazardous to health; late-onset effects of
      exposure to ionizing radiation (IR) pose risks to the lens, and are associated
      with other non-cancerous diseases. Individuals occupationally exposed to low-dose
      IR are prone to developing eye cataracts. Cytogenetic evaluations suggest that IR
      is associated with chromosomal aberrations in occupationally exposed individuals.
      However, data regarding the association between chromosomal aberrations in
      cataract patients and occupational exposure to IR is scarce. Therefore, we aimed
      to report the characteristics of chromosomal aberrations in cataract patients
      from a Chinese population, occupationally exposed to IR. We found that the
      average age and frequency of numerical chromosomal aberrations were significantly
      lower in the exposed patients as compared with that in the non-exposed patients.
      In addition, the frequencies of dicentric and acentric chromosomes were
      significantly higher in the exposed patients as compared with those in the non
      exposed patients. Therefore, chronic occupational exposure to IR affects cataract
      development in the Chinese population. The age of cataract patients exposed to IR
      was significantly lower than the age of cataract onset in normal individuals.
      Based on this study, we suggest that there is an urgent need for improved
      radiation safety and eye protection in individuals exposed to IR in the work
      place.

PMID- 27706731
TI  - Association of CD4 SNPs with fat percentage of Holstein cattle.
AB  - Cluster of differentiation 4 gene (CD4) is well known for its role in immunity,
      but its effects on production traits remain to be elucidated. The present study
      was designed to explore single nucleotide polymorphisms (SNPs) in the exons,
      flanking introns, and promoter of CD4, as well as to analyze their effects on
      milk production traits (percentage of protein, fat, and lactose; mastitis
      indicator traits somatic cell count; and somatic cell score). A total of 10 SNPs,
      including eight in the exon and two in the intron regions, were identified using
      pooled DNA sequencing. These SNPs were screened in a population of 258 Chinese
      Holstein using the SNaPshot technique. We analyzed the effects of SNPs, parity,
      herd, year, and season of calving on the production and mastitis indicator
      traits. Our analysis revealed two haplotypes and strong linkage disequilibrium
      (D' > 0.97) among all SNPs. All 10 SNPs were significantly associated with fat
      percentage (P < 0.01). Cows homozygous for the wild-type genotypes had higher fat
      percentages than those with the other genotypes. The dominant and additive
      effects were also significant for fat percentage (P < 0.05). These results
      suggest that CD4 plays a role in production traits as well as in immune function.
      The identified SNPs could be used as genetic markers for selection of dairy cows
      with improved fat percentage. We propose further studies of these SNPs in a
      larger population as well as further investigations of the function of this gene.

PMID- 27706732
TI  - Changes in expression of specific miRNAs and their target genes in repair of
      exercise-induced muscle injury in rats.
AB  - The effects of muscle-specific miRNAs in the repair of exercise-induced muscle
      injury were investigated by examining the changes in their expression and that of
      the target genes in rat skeletal muscle. Two-month-old agile male rats were
      randomly divided into exercise and static control groups, the former subdivided
      into 0-h, 6-h, 12-h, 1-day, 2-day, 3-day, 1-week, and 2-week groups based on time
      after exercise. Left gastrocnemii of rats were hematoxylin-eosin stained whereas
      the right gastrocnemii were used for expression analysis of muscle-specific
      miRNAs (miR-1 and miR-206) and their target genes, Cx43 and HDAC. Cellular
      swelling and increased cell volume and intercellular spaces were observed
      histologically in the 0-h group. Unlike the control group, cells continued to
      swell whereas intercellular spaces decreased slightly, in the 6-h, 12-h, 1-day,
      and 2-day groups. Cell swelling was most serious in the 3-day group. In the 1
      week group, inflammatory cell infiltration decreased and in the 2-week group,
      repair was almost complete. The differences in miR-1 expression between the
      groups were neither obvious nor significant. miR-206 expression increased;
      however, it differed significantly from that in group C only in the 1-week group.
      Cx43 and HDAC4 mRNA expression first decreased and then increased compared to
      that in the control group; differences in HDAC4 mRNA expression were significant
      in the 1-week group. Compared to the control group, the differences in Cx43
      protein levels were significant in the 0-h and 3-day groups. Thus, miR-206 and
      Cx43 are involved in the repair of exercise-induced muscle injury.

PMID- 27706733
TI  - Selection index using the graphical area applied to sugarcane breeding.
AB  - This study aimed to develop a multivariate selection index based on the graphical
      area of a polygon formed by standardized values, also known as radar chart. This
      methodology may be used to assist selection of superior genotypes in sugarcane
      breeding programs. Seven technological traits in 37 sugarcane genotypes were
      evaluated. An area index (AI) was constructed and the resulting polygon areas
      were used to rank genotypes under selection. In this study, we propose the use of
      restricted maximum likelihood to estimate genetic parameters and mixed model
      equations to predict genotypic and breeding values. The area of each polygon was
      calculated for phenotypic, genotypic, and estimated breeding values. Thereby, the
      genotypes with larger area can be selected based on a detailed a posteriori
      evaluation of the radar charts. The proposed AI can be adjusted based on the
      breeders' specific interests, it is perfectly useful in other crops, and may also
      be applied to studies on genotype-environment interactions. Moreover, AI is a
      powerful tool that can evaluate trait stability of genotypes based on slight
      differences in the area formed by each genotype. Hence, this method is easy to
      apply and shows great potential for use in sugarcane breeding programs as well as
      in other breeding programs.

PMID- 27706734
TI  - Association between miR-137 polymorphism and risk of schizophrenia: a meta
      analysis.
AB  - miR-137, a brain-enriched microRNA, is involved in the control of neuronal
      proliferation, differentiation, and dendritic arborization, all of which are
      important for proper neurogenesis and relevant to schizophrenia. miR-137 is also
      known to regulate many genes implicated in schizophrenia risk. Although reports
      have associated the miR-137 polymorphism rs1625579 with this disease, their
      results have been inconsistent. The aim of this meta-analysis was to evaluate the
      relationship between rs1625579 and schizophrenia. Data were obtained from an
      electronic database, and pooled odds ratios (ORs) with 95% confidence intervals
      (95%CI) were used to test the association using the RevMan 5.3 software. Twelve
      case-control studies comprising 11,583 cases and 14,315 controls were included.
      An estimated lambda value of 0.46 was recorded, suggesting that a codominant
      model of inheritance was most likely. A statistically significant association was
      established under allelic (T vs G: OR = 1.15, 95%CI = 1.10-1.21, P < 0.001) and
      homogeneous codominant models (TT vs GG: OR = 1.32, 95%CI = 1.13-1.54, P <
      0.001), but no such relationship was detected using the heterogeneous codominant
      model (GT vs GG: OR = 1.14, 95%CI = 0.97-1.34, P = 0.11). This meta-analysis
      demonstrates that the rs1625579 miR-137 genetic variant significantly increases
      schizophrenia risk.

PMID- 27706735
TI  - Development of a transposon-based marker system for mutation breeding in sorghum
      (Sorghum bicolor L.).
AB  - Under certain circumstances, transposable elements (TE) can create or reverse
      mutations and alter the genome size of a cell. Sorghum (Sorghum bicolor L.) is
      promising for plant transposon tagging due to its small genome size and its low
      content of repetitive DNA. We developed a marker system based on targeted region
      amplification polymorphisms (TE-TRAP) that uses the terminal inverted repeats
      (TIRs) of transposons. A total of 3816 class 2 transposons belonging to the
      PIF/Harbinger family were identified from the whole sorghum genome that produced
      five primers, including eight types of TIRs. To define the applicability and
      utilization of TE-TRAP, we used 21 individuals that had been bred after ?-ray
      irradiation. In total, 31 TE-TRAP, 16 TD, and 21 AFLP primer combinations
      generated 1133, 223, and 555 amplicons, respectively. The percent polymorphic
      marker was 62.8, 51.1, and 59.3% for the TE-TRAP, TD, and AFLP markers,
      respectively. Phylogenetic and principal component analyses revealed that TE-TRAP
      divided the 21 individuals into three groups. Analysis of molecular variance
      suggested that TE-TRAP had a higher level of genetic diversity than the other two
      marker systems. After verifying the efficiency of TE-TRAP, 189 sorghum
      individuals were used to investigate the associations between the markers and the
      ?-ray doses. Two significant associations were found among the polymorphic
      markers. This TE-based method provides a useful marker resource for mutation
      breeding research.

PMID- 27706736
TI  - Morphological and molecular characterization of Cladosporium cladosporioides
      species complex causing pecan tree leaf spot.
AB  - The objective of this study was to characterize species of the Cladosporium
      cladosporioides complex isolated from pecan trees (Carya illinoinensis) with
      symptoms of leaf spot, based on morphological and molecular approaches.
      Morphological attributes were assessed using monosporic cultures on potato
      dextrose agar medium, which were examined for mycelial growth, sporulation,
      color, and conidia and ramoconidia size. Molecular characterization comprised
      isolation of DNA and subsequent amplification of the translation elongation
      factor 1alpha (TEF-1alpha) region. Three species of the C. cladosporioides
      complex were identified: C. cladosporioides, Cladosporium pseudocladosporioides,
      and Cladosporium subuliforme. Sporulation was the most important characteristic
      differentiating species of this genus. However, morphological features must be
      considered together with molecular analysis, as certain characters are
      indistinguishable between species. TEF-1alphacan be effectively used to identify
      and group isolates belonging to the C. cladosporioides complex. The present study
      provides an important example of a methodology to ascertain similarity between
      isolates of this complex causing leaf spot in pecan trees, which should
      facilitate future pathogenicity studies.

PMID- 27706737
TI  - Association between the CDH1-472delA and -160C>A polymorphisms and diffuse and
      intestinal gastric cancer in a Mexican population.
AB  - Gastric cancer (GC), the third leading cause of cancer-related deaths in Mexico
      and worldwide, can be classified into diffuse (DGC) or intestinal (IGC) types
      based on its histological characteristics. DGC is characterized by reduced
      expression of the cell adhesion protein E-cadherin, which is encoded by CDH1. The
      -472delA (rs5030625) and -160C>A (rs16260) polymorphisms in CDH1 induce a
      decrease in gene transcription; in fact, these mutated alleles have been
      associated with GC in some populations, with conflicting results. The aim of this
      study was to determine the association between the CDH1 -472delA and -160C>A
      polymorphisms and DGC and IGC in Mexican patients. The study was conducted in 24,
      23, 48, and 93 individuals with DGC and IGC, without GC (control), and belonging
      to the general Mexican population (GMP), respectively. The genotypes were
      obtained by polymerase chain reaction - restriction fragment length polymorphism
      and the obtained data analyzed using Arlequin 3.1. The frequencies of the mutated
      allele (A) of -472delA were 0.326, 0.318, 0.284, and 0.296 in the DGC, IGC,
      control, and GMP groups, respectively, and those of the -160C>A polymorphism were
      0.174, 0.318, 0.313, and 0.280, respectively. The genotype and allele frequencies
      of the two polymorphisms did not differ significantly (P > 0.05) among DGC, IGC,
      and control subjects. Therefore, we concluded that the CDH1 -472delA and -160C>A
      polymorphisms are not associated with DGC or IGC in patients from western Mexico.

PMID- 27706738
TI  - Molecular cloning and functional characterization of cyclin E and CDK2 from
      Penaeus monodon.
AB  - Reduced reproductive performance of the black tiger shrimp (Penaeus monodon) has
      caused economic losses and hampered the fishing industry. Detailed investigation
      of the molecular mechanism by which the cell cycle is regulated in this organism
      is needed to understand the development and maturation of ovaries and oocytes,
      with a view to improving reproductive capacity. Cell cycle progression is mainly
      determined by cyclin-dependent kinase (CDK) and cyclin complexes, the cyclin
      E/CDK2 complex playing a key role in G1/S transition. However, knowledge of the
      interplay between cyclin E and CDK2 in invertebrates remains limited. In this
      study, full-length P. monodon cyclin E (Pmcyclin E) and CDK2 (PmCDK2) sequences
      were cloned. The open reading frame of Pmcyclin E was 1263 bp in length and
      encoded a 47.9-kDa protein, while that of PmCDK2 was 921 bp, encoding a protein
      of 34.9 kDa. Recombinant cyclin E and CDK2 proteins were expressed in Escherichia
      coli and purified by Ni-chelating affinity chromatography. In addition, a pull
      down assay was performed to identify any interaction between Pmcyclin E and
      PmCDK2. This research provides a basis for the study of the functional mechanisms
      of the cyclin E/CDK2 complex in shrimp, further enriching our knowledge of
      invertebrate cell cycle regulation.

PMID- 27706739
TI  - Polymorphisms in the DGAT1 gene in buffaloes (Bubalus bubalis) in the Amazon.
AB  - Water buffaloes (Bubalus bubalis) are quite well adapted to climatic conditions
      in the Amazon, and in this biome, they are noted for the considerable amount of
      meat and milk they produce and how hard they are able to work. Because of a lack
      of research dedicated to improving the rearing of buffaloes in the Amazon, the
      objective of this study was to genetically characterize the Murrah and
      Mediterranean breeds, as well as a mixed-breed population, based on polymorphisms
      in the diacylglycerol O-acyltransferase 1 gene (DGAT1), and associate the
      genotypes with milk production. By using the polymerase chain reaction-single
      strand conformation polymorphism technique, the alleles A (0.79), B (0.20), and D
      (0.01) were found in the Murrah breed. In the Mediterranean and mixed-breed
      buffaloes, we found alleles A (0.69) and (0.77) and B (0.31) and (0.23),
      respectively. The Murrah breed had the genotypes AA (0.63), AB (0.29), BB (0.05),
      and AD (0.03), and the Mediterranean and mixed-breed buffaloes had the genotypes
      AA (0.44) and (0.61), AB (0.50) and (0.31), and BB (0.06) and (0.08),
      respectively. For the Murrah, Mediterranean, and mixed-breed buffaloes,
      respectively, the expected heterozygosity values were 0.34, 0.43, and 0.35, the
      inbreeding coefficients were 0.78, -0.15, and 0.17, and the Hardy-Weinberg
      probabilities were 0.70, 0.67, and 0.52. The genotypes evaluated did not have an
      effect on milk production; however, the single nucleotide polymorphisms can be
      used in studies on genetic variability.

PMID- 27706740
TI  - An improved DNA marker technique for genetic characterization using RAMP-PCR with
      high-GC primers.
AB  - Random amplified polymorphic DNA (RAPD) is a widely used molecular marker
      technique. As traditional RAPD has poor reproducibility and productivity, we
      previously developed an improved RAPD method (termed RAMP-PCR), which increased
      the reproducibility, number of bands, and efficiency of studies on polymorphism.
      To further develop the efficiency of this method, we used high-GC content primers
      for improved RAMP-PCR with DNA samples from Lonicera japonica. Comparison of
      amplification profiles obtained by standard RAPD primers with those obtained by
      regular PCR and RAMP-PCR, and high-GC primers with regular PCR and RAMP-PCR
      showed that the average number of bands and polymorphisms per primer gradually
      and significantly increased (from 6.4 to 15.0 and from 4.6 to 10.2,
      respectively). Cluster dendrograms showed similar results, indicating that this
      new method is consistent and reproducible. A total of 22 samples from different
      species, including plants, animals, and humans, were used for RAMP-PCR with high
      GC primers. Multiple bands were successfully amplified from all samples,
      demonstrating that this method is a reliable technique with consistent results
      and may be of general interest in studies on different genera and species. We
      developed highly effective DNA markers, which can provide a more effective and
      potentially valuable approach than traditional RAPD for the genetic
      identification of various organisms, particularly of medicinal plants.

PMID- 27706741
TI  - Identification and characterization of genes related to cellulolytic activity in
      basidiomycetes.
AB  - Enzymes produced by basidiomycetes that are involved in the cellulose degradation
      process, and their respective codifying genes, must be identified to facilitate
      the development of novel biotechnological strategies and applications in the agro
      industry. The objective of this study was to identify prospective cellulase
      producing genes and characterize their cellulolytic activity, in order to
      elucidate the potential biotechnological applications (with respect to vegetal
      residues) of basidiomycetes. The basidiomycete strains Lentinula edodes U8-1,
      Lentinus crinitus U9-1, and Schizophyllum commune U6-7 were analyzed in this
      study. The cellulolytic activities of these fungi were evaluated based on the
      halo formation in carboxymethyl cellulose culture medium after dyeing with Congo
      red. The presence of cellulase-codifying genes (cel7A, cel6B, cel3A, and egl) in
      these fungal strains was also evaluated. L. edodes and S. commune presented the
      highest cellulolytic halo to mycelial growth radius ratio, followed by L.
      crinitus. Four genes were amplified in the L. edodes strain, whereas three and
      one genes were isolated from L. crinitus and S. commune, respectively. The cel6B
      gene (L. edodes) presented the conserved domain glyco_hydro_6 and characterized
      as cellobiohydrolase gene. The results of this study contribute to the existing
      knowledge on cellulases in basidiomycetes, and serve as a basis for future
      studies on the expression of these genes and the characterization of the
      catalytic activity of these enzymes. This allows for better utilization of these
      fungi in degrading vegetal fibers from agro-industrial residues and in other
      biotechnological applications.

PMID- 27706742
TI  - Characterization and gene cloning of the rice (Oryza sativa L.) dwarf and narrow
      leaf mutant dnl3.
AB  - The dwarf and narrow-leaf rice (Oryza sativa L.) mutant dnl3 was isolated from
      the Japonica cultivar Zhonghua 11 (wild-type). dnl3 exhibited pleiotropic
      developmental defects. The narrow-leaf phenotype resulted from a marked reduction
      in the number of vascular bundles, while the dwarf stature was caused by the
      formation of foreshortened internodes and a reduced number of parenchyma cells.
      The suggestion that cell division is impaired in the mutant was consistent with
      the transcriptional behavior of various genes associated with cell division. The
      mutant was less responsive to exogenously supplied gibberellic acid than the wild
      type, and profiling the transcription of genes involved in gibberellin synthesis
      and response revealed that a lesion in the mutant affected gibberellin signal
      transduction. The dnl3 phenotype was inherited as a single-dominant gene, mapping
      within a 19.1-kb region of chromosome 12, which was found to harbor three open
      reading frames. Resequencing the open reading frames revealed that the mutant
      carried an allele at one of the three genes that differed from the wild-type
      sequence by 2-bp deletions; this gene encoded a cellulose synthase-like D4
      (CSLD4) protein. Therefore, OsCSLD4 is a candidate gene for DNL3. DNL3 was
      expressed in all of the rice organs tested at the heading stage, particularly in
      the leaves, roots, and culms. These results suggest that DNL3 plays important
      roles in rice leaf morphogenesis and vegetative development.

PMID- 27706743
TI  - Analysis of pecan cultivars Mahan and Western in East China.
AB  - Pecan (Carya illinoensis) has been introduced to East China for over one hundred
      years, but its planting is still only occurring at a small scale. The key
      limiting factor is its low yield. To enhance the yield pecan in East China, two
      pecan cultivars, Mahan and Western, were examined. Twenty traits describing
      phasic development, yield, nut quality, and cultural practice were investigated.
      We found that pecan cultivar Mahan gives a higher yield and nut quality than
      cultivar Western. We recommend interplanting of cultivar Pawnee to act as a
      pollinator tree. Appropriate cultivation practices that can be implemented to
      enhance fruit yield of cultivars Mahan and Western include soil-applied
      paclobutrazol (PBZ) at certain concentrations, pinching, and supplementary
      pollination. For example, the addition of 1.25 g/m2 of PBZ inhibits pecan branch
      growth and stimulates short bearing branches, which promotes fruit yield. We
      found that soil-applied PBZ reached optimal performance 82 days after
      application. A pinching length of 40 cm resulted in a fruit yield increase. In
      addition, grafting and transplantation may promote male flowering, but delays
      female flowering. These cultural practices may provide insights that can be used
      to improve pecan cultivation in East China.

PMID- 27706744
TI  - Novel mutations in the FUCA1 gene that cause fucosidosis.
AB  - Fucosidosis is a rare lysosomal storage disorder inherited in an autosomal
      recessive manner. Its estimated frequency is below 1 in 200,000 live births. Its
      clinical phenotypes include progressive neurological and mental deterioration,
      coarse facial features, growth retardation, visceromegaly, angiokeratomas, and
      seizures. The disease is caused by mutations in the FUCA1 gene that lead to
      deficiency of a-L-fucosidase. Here, we describe the clinical and molecular
      features of a Thai boy with fucosidosis. Whole exome sequencing and array-based
      comparative genomic hybridization analysis revealed that the patient was compound
      heterozygous for a single base-pair deletion (c.670delC; p.P224LfsX2) inherited
      from his father, and a 3281-base-pair deletion covering exon 3 inherited from his
      mother. Neither mutation has been reported before so the FUCA1 mutational
      spectrum is herein expanded.

PMID- 27706745
TI  - Influence of CYP2C19 on Helicobacter pylori eradication in Brazilian patients
      with functional dyspepsia.
AB  - The aim of this study was to examine the effect of polymorphisms in the
      cytochrome P450 (CYP) 2C19 gene (CYP2C19) on the Helicobacter pylori eradication
      rate in Brazilian patients with functional dyspepsia. Adults diagnosed with
      functional dyspepsia based on the ROME III criteria and infected with H. pylori
      were recruited to this study. The patients were subjected to gastrointestinal
      endoscopy and the H. pylori status was defined when both urease test and
      histopathology results were negative or positive. The patients were treated with
      proton pump inhibitor-based triple therapy (omeprazole, amoxicillin, and
      clarithromycin). CYP2C19*2 and CYP2C19*3 were genotyped by polymerase chain
      reaction-restriction fragment length polymorphism. One hundred and forty-eight
      patients (81.8% women) with a mean (+/- SD) age of 46.1 (12.2) years were
      included in this study. Based on the CYP2C19 genotypes, the patients were
      classified as homozygous extensive metabolizer (HomEM; 67.6%), heterozygous
      extensive metabolizer (HetEM; 26.3%), or poor metabolizer (PM; 6.1%). The H.
      pylori eradication rates in patients with HomEM, HetEM, and PM were 85.0, 89.7,
      and 100.0% (P = 0.376), respectively. The included study population comprised a
      high frequency of patients carrying the HomEM genotype. Although the genotypes of
      CYP2C19 variants were not statistically significant, the results of this study
      suggest a possible effect of the PM genotype on the efficacy of H. pylori
      eradication.

PMID- 27706746
TI  - Microsporogenesis analysis validates the use of artificially tetraploidized
      Brachiaria ruziziensis in breeding programs.
AB  - The genus Brachiaria contains species that have great economic importance in the
      Brazilian agricultural sector, as they enable cattle ranching on acid and poor
      soils with species that are resistant to spittlebugs and form crop-livestock
      forest integration systems. The genus mainly consists of tetraploid (2n = 4x =
      36) and apomictic species such as B. decumbens and B. brizantha. Sexuality is
      found in diploid species (2n = 2x = 18) such as B. ruziziensis. Interspecific
      hybridization between species of interest is possible by the artificial
      tetraploidization of B. ruziziensis and the subsequent hybridization with
      genotypes of B. brizantha and B. decumbens. Therefore, tetraploidized plants have
      to have normal meiosis or low rates of irregularities, as well as produce viable
      pollen grains. The objective of this study was to compare meiosis and pollen
      grain viability and morphology in artificially tetraploidized B. ruziziensis with
      that of descendants generated from crossing and selfing. The frequency of meiotic
      abnormalities ranged from 4.43 to 11%, and pollen viability ranged from 61 to
      85%. Abnormalities were detected from prophase I to the tetrad stage with a
      variable frequency between the genotypes. The meiotic behavior of the
      artificially tetraploidized plants was little affected, and the pollen viability
      of the genotypes was high. Regarding pollen grain ultrastructure, there were no
      variations or morphological changes in the different genotypes. The genotypes
      have meiotic stability and high pollen viability, and can be incorporated into
      Brachiaria breeding programs.

PMID- 27706747
TI  - Physiological analysis and transcriptome comparison of two muskmelon (Cucumis
      melo L.) cultivars in response to salt stress.
AB  - Melon (Cucumis melo L.) is an important vegetable crop that ranks second in salt
      tolerance among the Cucurbitaceae. Previous studies on the two muskmelon
      cultivars 'Bing XueCui' (BXC) and 'Yu Lu' (YL) revealed that they had different
      characteristics under salt stress, but the molecular basis underlying their
      different physiological responses is unclear. Here, we combined a physiological
      study with a genome-wide transcriptome analysis to understand the molecular basis
      of genetic variation that responds to salt stress in the melon. BXC performed
      better under salt stress than YL in terms of biomass and photosynthetic
      characteristics, because it exhibited less reduction in transpiration rate, net
      photosynthesis rate, and stomatal conductance under 150-mM NaCl stress than YL. A
      transcriptome comparison of the leaves of the cultivars revealed that 1171 genes
      responded to salt stress in BXC while 1487 genes were identified as salt-stress
      responsive in YL. A real-time polymerase chain reaction analysis of 12 of the
      responsive genes revealed that there was a strong, positive correlation with RNA
      sequencing data. The genes were involved in several pathways, including
      photosynthesis, the biosynthesis of secondary metabolites, metabolism, and plant
      hormone signal transduction, and their expression levels differed between the two
      cultivars in response to salt stress. This study provides a molecular perspective
      of two melon cultivars in response to salt stress, and its results could be used
      to investigate the complex molecular mechanisms underlying salt tolerance in the
      melon.

PMID- 27706748
TI  - Classification and phylogenetic analysis of Chinese hawthorn assessed by plant
      and pollen morphology.
AB  - The Chinese hawthorn (Crataegus pinnatifida Bge. var. major N.E.Br.) is uniquely
      originated in northern China. The ecological and horticultural importance of
      Chinese hawthorn is considerable and some varieties are valued for their fruit or
      medicine extracts. Its taxonomy and phylogeny remain poorly understood. Apart
      from general plant morphological traits, pollen is an important trait for the
      classification of plants and their evolutionary origin. However, few studies have
      investigated the pollen of Chinese hawthorn. Here, an analysis of plant and
      pollen morphological characteristics was conducted in 57 cultivars from the
      Shenyang region. Thirty plant morphological characters and nine pollen grain
      characters were investigated. The plant morphological analysis revealed that the
      coefficient of variation for 13 traits was >20%, which indicates a high degree of
      variability. We also found that the pollen grains varied greatly in size, shape
      (from prolate to perprolate), and exine pattern (striate-perforate
      predominantly). The number of apertures was typically three. Based on these
      findings, we suggest that pollen morphology associated with plant morphological
      traits can be used for classification and phylogenetic analysis of Chinese
      hawthorn cultivars. In sum, our results provide new insights and constitute a
      scientific basis for future studies on the classification and evolution of
      Chinese hawthorn.

PMID- 27706750
TI  - Single base substitution causing the fragrant phenotype and development of a type
      specific marker in aromatic coconut (Cocos nucifera).
AB  - The fragrance gene, betaine aldehyde dehydrogenase 2 (Badh2), has been well
      studied in many plant species. The objectives of this study were to clone Badh2
      and compare the sequences between aromatic and non-aromatic coconuts. The
      complete coding region was cloned from cDNA of both aromatic and non-aromatic
      coconuts. The nucleotide sequences were highly homologous to Badh2 genes of other
      plants. Badh2 consisted of a 1512-bp open reading frame encoding 503 amino acids.
      A single nucleotide difference between aromatic and non-aromatic coconuts
      resulted in the conversion of alanine (non-aromatic) to proline (aromatic) at
      position 442, which was the substrate binding site of BADH2. The ring side chain
      of proline could destabilize the structure leading to a non-functional enzyme.
      Badh2 genomic DNA was cloned from exon 1 to 4, and from exon 5 to 15 from the two
      coconut types, except for intron 4 that was very long. The intron sequences of
      the two coconut groups were highly homologous. No differences in Badh2 expression
      were found among the tissues of aromatic coconut or between aromatic and non
      aromatic coconuts. The amino acid sequences of BADH2 from coconut and other
      plants were compared and the genetic relationship was analyzed using MEGA 7.0.
      The phylogenetic tree reconstructed by the Bayesian information criterion
      consisted of two distinct groups of monocots and dicots. Among the monocots,
      coconut (Cocos nucifera) and oil palm (Elaeis guineensis) were the most closely
      related species. A marker for coconut differentiation was developed from one-base
      substitution site and could be successfully used.

PMID- 27706749
TI  - Case Report Identification of a novel SLC45A2 mutation in albinism by targeted
      next-generation sequencing.
AB  - Albinism is a diverse group of hypopigmentary disorders caused by multiple
      genetic defects. The genetic diagnosis of patients affected with albinism by
      Sanger sequencing is often complex, expensive, and time-consuming. In this study,
      we performed targeted next-generation sequencing to screen for 16 genes in a
      patient with albinism, and identified 21 genetic variants, including 19 known
      single nucleotide polymorphisms, one novel missense mutation (c.1456 G>A), and
      one disease-causing mutation (c.478 G>C). The novel mutation was not observed in
      100 controls, and was predicted to be a damaging mutation by SIFT and Polyphen.
      Thus, we identified a novel mutation in SLC45A2 in a Chinese family, expanding
      the mutational spectrum of albinism. Our results also demonstrate that targeted
      next-generation sequencing is an effective genetic test for albinism.

PMID- 27706751
TI  - Association between peptidyl arginine deiminase 4 (PADI4)-104C/T polymorphism and
      rheumatoid arthritis: a meta-analysis in the Chinese population.
AB  - The correlation between the -104C/T polymorphism in the peptidyl arginine
      deiminase 4 (PADI4) gene and rheumatoid arthritis (RA) risk has been analyzed in
      several studies. However, the results are inconclusive and remain to be confirmed
      in several ethnic groups. The effect of the PADI4-104C/T polymorphism on RA risk
      in the Chinese population was evaluated in a meta-analysis. Studies with dates of
      publication up to July 2015 conforming to the inclusion criteria were retrieved
      from PubMed and Chinese databases. The associations were assessed with pooled
      odds ratios (ORs) and 95% confidence intervals (CIs). Ten studies, including 2119
      RA cases and 1962 controls, that conformed to the study criteria were included in
      this analysis. The overall analysis indicated a significant association between
      the PADI4-104C/T polymorphism and RA risk in the Chinese population (T vs C: OR =
      1.45, 95%CI = 1.18-1.78; TT vs CC: OR = 1.49, 95%CI = 1.24-1.80; TT vs CC+CT: OR
      = 1.28, 95%CI = 1.08-1.51; TT+CT vs CC: OR = 1.75, 95%CI = 1.30-2.37). Analysis
      of data stratified by the geographic area and source of controls revealed that
      the PADI4-104C/T polymorphism was significantly associated with RA risk in a
      North Chinese population. In conclusion, the results of this meta-analysis
      indicated that the PADI4-104C/T variants could influence the risk of RA in the
      Chinese population; further studies in other ethnic groups are required to draw
      definite conclusions.

PMID- 27706753
TI  - Identification of SNPs in growth-related genes in Colombian creole cattle.
AB  - Colombian creole cattle have important adaptation traits related to heat
      tolerance and reproductive and productive efficiency. Romosinuano (ROMO) and
      Blanco Orejinegro (BON) are the most common breeds used by Colombian cattle
      breeders. Growth traits are of prime importance in these animals, which are
      mainly raised for beef production. Genes encoding growth hormone, growth hormone
      receptor, homeobox protein, insulin growth factor binding protein 3, leptin, and
      myostatin have been associated with physiological growth pathways in cattle and
      other species. We therefore aimed to identify single nucleotide polymorphisms
      (SNPs) within these genes in ROMO, BON, and Zebu cattle. DNA regions of these
      genes were sequenced in 386 animals; 47 new SNPs were found, of which 14 were
      located in the exonic regions, thereby changing the protein sequence. An
      association of SNPs with weaning weight (WW), daily weight gain at weaning (DWG),
      and weight at 16 months (W16M) traits was deduced. The genetic analysis revealed
      several SNPs related to these traits. The SNP GhRE06.2 had a significant
      association with WW and the SNP Lep03.4 was highly associated with DWG and W16M.
      Other polymorphisms were significantly associated with WW and DWG, although they
      did not surpass the Bonferroni significance threshold. The new mutations
      identified may indicate important points of genetic control in the DNA that could
      be responsible for changes in the expression of the analyzed traits. These SNPs
      might be used in future breeding programs to improve the productive performance
      of cattle in beef farms.

PMID- 27706752
TI  - Biometric analysis of arabica coffee grown in low potassium nutrient solution
      under greenhouse conditions.
AB  - Genetic parameters and associations between morpho-agronomic traits and
      nutritional efficiencies of arabica coffee cultivars were estimated to identify
      promising traits to assist in the selection of coffee genotypes efficient in
      potassium use, under limiting conditions of this nutrient. The experiment was
      conducted in a greenhouse with 20 arabica coffee cultivars grown in nutrient
      solution with a low potassium level (1.5 mM), using a randomized block design
      with three replicates. The traits evaluated were plant height, number of leaves,
      number of nodes, internode length, stem diameter, leaf area, rooting efficiency,
      potassium absorption efficiency, potassium translocation efficiency, biomass
      production efficiency, and potassium use efficiency. Genetic variability among
      coffee cultivars for all the evaluated traits was found. The phenotypic variance
      for all traits showed a higher contribution of genetic variance compared to
      environmental variance. Plant height, internode length, stem diameter, leaf area,
      biomass production efficiency, and potassium use efficiency had a genotypic
      determination coefficient (H2) above 80% and variation index greater than one.
      Leaf area and stem diameter had significant and positive genetic correlations
      with rooting, biomass production, and potassium use efficiencies. Stem diameter
      has great potential for use in breeding programs with a goal of indirect
      selection of cultivars that have greater potassium use efficiency in environments
      with restrictions of this nutrient.

PMID- 27706754
TI  - Development of the first polymorphic microsatellite markers for the Roman snail
      Helix pomatia L., 1758 (Helicidae) and cross-species amplification within the
      genus Helix.
AB  - The terrestrial snail Helix pomatia (Gastropoda: Stylommatophora: Helicidae) is
      one of the largest gastropod species in Europe. This species is strictly
      protected in some European Union countries; however, at the same time, it is also
      farmed and commercialized for human consumption. Here, we describe 11
      microsatellite markers that are very useful in population genetic studies for
      assessing the status of both wild and farmed populations of this species of
      community interest. The microsatellites were isolated using 454 pyrosequencing
      technologies and 11 primer pairs were selected and used for genotyping an H.
      pomatia population and also checked for cross-species amplification on H. lucorum
      and H. lutescens specimens. The number of alleles per locus ranged from 3 to 13
      and observed heterozygosity was between 0.458 and 0.917. Seven of these loci were
      polymorphic in H. lucorum, and four in H. lutescens. This set of nuclear markers
      provides a powerful tool for population genetic studies of this species of
      community interest, and also for closely related species. The described
      microsatellite markers should also facilitate the identification of populations
      of conservation concern.

PMID- 27706755
TI  - RNA applications for endophytic research.
AB  - Endophytic microorganisms, mainly bacteria and fungi, have intrinsic
      relationships with the host plants, involving complex chemical and genetic
      communication networks. The relationship among these organisms involves the
      development of regulatory mechanisms of gene expression that control their
      development and response to different interactions. Although RNA molecules are
      already being used in studies of microorganism diversity and taxonomy, for
      example, using comparisons of rRNA regions, they may also be useful tools in the
      exploration of gene regulation and modeling of other molecules, such as the
      analysis of microRNA and small interfering RNAs. Transcriptional profile analyses
      are capable of providing robust information on biosynthetic pathways, genes
      involved in the interaction and differential production of metabolites by
      endophytes, using RNA-seq approaches. In-depth studies of RNA types and their
      functions in endophytes may provide valuable information that can be used for
      biotechnological manipulation of microorganisms to produce metabolites,
      bioremediation, biological control of pathogens, and decrease plant diseases,
      among other economically important applications. Our study highlights the present
      state of knowledge of studies involving endophytes, RNA molecules, and future
      perspectives.

PMID- 27706756
TI  - Molecular phylogeny of the Bactrian camel based on mitochondrial Cytochrome b
      gene sequences.
AB  - The Bactrian camel is an important domesticated animal providing milk, meat, and
      other products in desert countries. In this study, 111 individuals representing
      11 domestic Bactrian camel breeds from China, Mongolia, Russia, and one wild
      Bactrian camel group from Mongolia were selected for the preparation of
      mitochondrial DNA. The 1140-bp fragments of the cytochrome b gene (Cytb) were
      amplified by polymerase chain reaction and sequenced directly. Sequences of the
      92 domestic and 19 wild Bactrian camel samples were analyzed with DNASTAR, and a
      phylogenic tree was constructed using MEGA. The analysis revealed sixteen
      haplotypes among the samples that were divided into two haplogroups: a domestic
      haplogroup (H1-H13, H15, and H16) and a wild haplogroup (H14). Haplotype
      diversity values were from 0.356 in the HosZogdort, to 0.889 in the Sunit
      Bactrian camel breed. The Sunit breed displayed the highest nucleotide diversity
      value (0.00115), and the HosZogdort breed had the lowest value (0.00031). All
      domestic Bactrian camels formed a single monophyletic lineage that is the sister
      group to wild Bactrian camels, a finding consistent with a single domestication
      event and independent maternal inheritance since domestication. In addition, the
      most common mitochondrial haplotypes (H1, H3, and H4) were shared between
      Chinese, Mongolian, and Russian domestic Bactrian camels, which indicated that
      there was no distinguishing geographic structure among the domestic breeds from
      these three regions. These findings provide important insights into patterns of
      relatedness among Bactrian camels from the Chinese, Mongolian, and Russian
      regions.

PMID- 27706758
TI  - JNK pathway and relative transcriptional factor were involved in ginsenoside Rh2
      mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells.
AB  - Ginsenoside Rh2 has been shown to have an anti-tumor effect on a wide range of
      cancers. A previous study has shown that ginsenoside Rh2 can inhibit the
      proliferation of the human lung adenocarcinoma A549 cell line in a dose-dependent
      manner by activating caspase-8/3 activity to promote apoptosis. However, the
      association of the JNK signaling pathways and transcription factors with
      ginsenoside Rh2 in the suppression of non-small cell lung cancer has not yet been
      reported. In this study, we found that ginsenoside Rh2 can activate the JNK/MAPKs
      signaling pathway and increase the phosphorylation and transcriptional activity
      of the transcription factors AP-1 and ATF2. Ginsenoside Rh2 also reduced the
      expression of transcription factors E2F1 and c-Myc. Furthermore, ginsenoside Rh2
      affected the expression levels of cyclin D1 and the CDK4 protein, which are key
      regulatory factors of the G1/S cyclin-dependent kinase. The anti-proliferative
      and induced apoptotic effects of ginsenoside Rh2 on A549 cell provide evidence to
      support the application of traditional Chinese medicine to lung cancer treatment.

PMID- 27706757
TI  - Cardiac damage and dysfunction in diabetic cardiomyopathy are ameliorated by
      Grx1.
AB  - Glutaredoxin 1 (Grx1) has been found to be an important endogenous antioxidant
      enzyme closely related to the pathogenesis of diabetes and cardiovascular
      diseases caused by oxidative stress. In this study, the functional changes of the
      Grx1 redox system in blood of hyperglycemic patients were examined. Furthermore,
      using a rat model of streptozotocin (STZ)- and high-fat-diet-induced type 2
      diabetes, we explored the correlation between functional changes of the Grx1
      redox system in the left ventricular tissue and blood of the diabetic rats.
      Moreover, we studied the protective effect of Grx1 against cardiac toxicity
      caused by the high-glucose-induced expression of cardiac matrix
      metalloproteinases (MMPs) in primary cultured cardiac fibroblasts. Finally, we
      investigated the protective effects and signaling regulatory mechanism of Grx1
      against diabetic cardiomyopathy (DCM) in terms of oxidative stress and NF-kB
      mediated fibrosis-associated signaling pathways. In the serum of hyperglycemic
      patients, Grx1 levels were elevated, total/protein thiol or sulfhydryl (Total
      SH/P-SH) levels were decreased, glutathione was downregulated, and oxidized
      glutathione was upregulated. In addition, in the left ventricular myocardium and
      blood of the diabetic rats, Grx1 levels were significantly increased and
      glutathione reductase and P-SH levels were decreased. Moreover, endogenous Grx1
      was highly expressed in cardiac fibroblasts during high-glucose treatment, and
      exogenous Grx1 can prevent DCM by controlling oxidative damage and MMP
      expression. These findings are suggestive of changes in the Grx1 redox system,
      and Grx1-regulated protein oxidative modifications may serve as molecular markers
      for diabetes caused by high-glucose-induced oxidative stress.

PMID- 27706759
TI  - In vitro inhibition of invasion and metastasis in colon cancer cells by TanIIA.
AB  - The purpose of this study was to investigate the effect of the traditional
      Chinese medicine TanIIA on the viability, invasion, and metastasis of SW480
      cells. SW480 cells were treated with TanIIA for 24 h, and MTT assays were
      performed to determine the effect of TanIIA on cell viability. Transwell
      transmembrane experiments were applied to test the effect of 1.0 mg/mL TanIIA on
      SW480 cell invasion and metastasis abilities. Western blotting was performed to
      determine the expression of the tumor cell metastasis proteins E-cadherin,
      vimentin, and MMP-9. The cell growth inhibition rates were 0%, 26 +/- 4.3%, 43.47
      +/- 4.0%, 63.0 +/- 5.5%, and 76.8 +/- 7.8% for treatment with 0, 0.5, 1.0, 2.0,
      and 5.0 mg/L TanIIA, respectively. The differences in the cell viability
      inhibitory rates among all groups were statistically significant (P < 0.05). The
      Transwell assay results indicated that SW620 cell invasion and metastasis
      abilities were strongly inhibited by 1.0 mg/mL TanII. The western blotting
      results showed that the expression of E-cadherin was significantly increased and
      that the expression levels of vimentin and MMP-9 were significantly decreased
      after treatment with 1.0 mg/mL TanII for 24 h (P < 0.05). Tan II can effectively
      inhibit the biological activity of colon cancer in vitro and prevent the invasion
      of colon cancer cells.

PMID- 27706760
TI  - Inbreeding depression in single, three way and double-cross hybrids of maize.
AB  - Currently, one of the acclaimed alternatives for increasing maize yield is
      accomplished through utilization of heterosis in hybrid cultivars. However, upon
      performing crosses between related pairs, there are losses due to inbreeding
      depression. Thus, the aim of this study was to estimate inbreeding depression and
      the contribution of loci in heterozygosity in different types of maize hybrids.
      Eight treatments were evaluated, considering the F1 and S0 generations of four
      commercial hybrids. A randomized block experimental design was used, with three
      replications, and plots consisting of two three-meter long rows at a spacing of
      0.50 m. The traits evaluated were plant height, first ear height and husked ear
      weight. For ear weight trait, there was a significant difference, where the
      treatments could be classified into three distinct groups. In this case, the
      single-cross hybrids AG7088 and 30F90Y exhibited greater depression through
      inbreeding due to the greater contribution of loci in heterozygosity and
      consequent predominance of deviations due to dominance.

PMID- 27706762
TI  - Genomic characterization and phylogenetic analysis of Chinese sacbrood virus
      isolated from Loess Plateau, China.
AB  - The complete genomic RNA of the Chinese sacbrood virus (CSBV) strain, which
      infects the honeybees in the Loess plateau, was sequenced and analyzed. The CSBV
      SX strain contains 8705 nucleotides, which includes a single large open reading
      frame (99-8681 nucleotides) encoding 2860 amino acids. A novel efficient
      identification method was used to investigate the samples infected by CSBV. The
      putative amino acid sequence alignment analysis showed that, except for some
      normal well characterized domains such as RNA helicase, RNA protease, and RNA
      dependent RNA polymerase domains, a calicivirus coat protein domain was
      identified at amino acids 493-564. Phylogenetic analysis indicated that CSBV-SX
      was closely related to CSBV-BJ, and this result was supported by nucleotide
      multiple sequence alignment and protein multiple sequence alignment analysis
      results. These differences in the CSBV-SX strain may be related to virus
      adaptation to the xerothermic, low relative humidity, and strong ultraviolet
      radiation conditions in the Loess Plateau.

PMID- 27706761
TI  - Correlation of acetabular chondrocyte apoptosis with caspase-3 and Bcl-2
      expression in developmental dislocations of the hip.
AB  - This study aimed to determine whether abnormal apoptosis is present in acetabular
      cartilage in early developmental dislocations of the hip (DDH), and if so,
      whether it is correlated with the expression of caspase-3 and Bcl-2. DDH was
      induced in 24 4-week-old New Zealand white rabbits. Acetabular cartilage
      specimens from the experimental and control groups were stained with hematoxylin
      and eosin (H&E). Animals from the experimental group developed acetabular
      dysplasia. Apoptotic chondrocytes were observed by ultrastructural electron
      microscopy and H&E. TUNEL assays revealed significantly greater acetabular
      chondrocyte apoptosis in the treated samples as compared to the control.
      Significantly higher caspase-3 expression and lower Bcl-2 expression were also
      measured in the DDH group compared with the control. We conclude that excessive
      apoptosis does occur in acetabular cartilage with DDH, and is positively
      correlated with high caspase-3 expression as well as low Bcl-2 expression.

PMID- 27706763
TI  - Role of GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms in the response to
      chemotherapy and overall survival of advanced non-small cell lung cancer.
AB  - We evaluated the association between GSTM1, GSTT1, and GSTP1 IIe105Val gene
      polymorphisms and treatment outcomes of advanced non-small cell lung carcinoma.
      Between January 2010 and December 2012, a total of 244 patients with non-small
      cell lung carcinoma were recruited from Yiwu Central Hospital. The GSTM1, GSTT1,
      and GSTP1 IIe105Val gene polymorphisms were analyzed by polymerase chain reaction
      restriction fragment length polymorphism and the results were statistically
      analyzed. Conditional regression analysis, showed that individuals carrying the
      null GSTM1 were associated with an increased risk of response to chemotherapy
      when compared to the present GSTM1 (odds ratio = 1.88, 95% confidence interval
      (CI) = 1.01-3.47). Moreover, the GG genotype of GSTP1 IIe105Val was associated
      with a better response to chemotherapy compared to the AA genotype (odds ratio =
      2.77, 95%CI = 1.14-6.64). The null GSTM1 genotype was associated with a lower
      risk of death from all causes when compared with the present GSTM1 genotype
      (hazard ratio = 2.16, 95%CI = 1.10-4.38). Moreover, the GG genotype of GSTP1
      IIe105Val was correlated with a reduced risk of death from all causes compared
      with the AA genotype (hazard ratio = 2.94, 95%CI = 1.11-8.68). In conclusion, we
      found that the null GSTM1 and the GG genotype of GSTP1 IIe105Val were correlated
      with a good response to chemotherapy and improved overall survival of advanced
      non-small cell lung carcinoma patients.

PMID- 27706764
TI  - Genetic diversity of Lippia sidoides Cham. and L. gracilis Schauer germplasm.
AB  - The conservation of plants in germplasm banks ensures the characterization and
      availability of these resources for future generations. The present study used
      DNA markers to obtain genetic information about germplasm collections of Lippia
      sidoides and L. gracilis, which are maintained in an Active Germplasm Bank (AGB).
      Genetic variability of samples in the AGB was assessed using 12 combinations of
      amplified fragment length polymorphism (AFLP) primers (EcoRI/MseI). Twenty simple
      sequence repeat primers designed for L. alba were tested to determine their
      transferability in L. sidoides and L. gracilis. The AFLP markers generated 789
      markers. The assessed loci exhibited a moderate Shannon diversity index (I =
      0.42) in both species, suggesting that the conserved accessions possess an
      intermediate level of genetic diversity. Twelve microsatellite loci amplified
      satisfactorily, and nine loci were polymorphic in each species. A total of 23,
      22, and 36 alleles, with an average of 2.5, 2.4, and 3.27 alleles per locus were
      identified for L. sidoides and L. gracilis accessions in the AGB, and Lippia sp
      sampled plants, respectively. Analyses of genetic structure permitted the
      identification of three different groups using both sets of markers, of which two
      were representative of L. sidoides. The information generated in this study may
      help to create, expand, and maintain collections of these species and may assist
      in genetic-breeding programs.

PMID- 27706766
TI  - Transformation of the CmACS-7 gene into melon (Cucumis melo L.) using the pollen
      tube pathway.
AB  - The aim of the present study was to develop a transformation system that may be
      useful for introducing agronomically and biotechnologically relevant traits into
      melon. The production of transplanted melon with maternal inheritance of the
      transgene could solve problems related to outcrossing between genetically
      modified crops and conventional crops or their wild relatives. By analyzing the
      main influencing factors systematically, the pollination time was ascertained and
      the pollen-tube pathway genetic transformation system was optimized. A screening
      system for resistant seeds from the T1 generation was established. The
      transformed seedlings were grown under standard field conditions and selected
      using a polymerase chain reaction-based analysis. The resistant plants were
      detected at a rate of 5%. These results indicate that enhanced production hastens
      the initiation of bisexual flowers, development of mature bisexual flowers, and
      fruit set in melon. We have established a melon transformation system based on
      the pollen-tube method.

PMID- 27706765
TI  - Role of IL-10 and TNF-alpha during Mycobacterium tuberculosis infection in murine
      alveolar macrophages.
AB  - Mycobacterium tuberculosis (Mtb) is known to be responsible for tuberculosis
      (TB), but the pathogenesis of this disease and the host defense mechanisms
      involved are, for the most part, poorly understood. In this study, we divided 30
      male C57BL/6 mice into control and infection groups, and following injection with
      physiological saline or Mtb, respectively, euthanized five mice from each group
      on days 1, 3, and 7. TNF-alpha and IL-10 levels were measured by enzyme-linked
      immunosorbent assay and flow cytometry, with the latter also being performed to
      assess apoptosis rates. Protein expression of STAT3 and its phosphorylated form
      (p-STAT3) was analyzed by western blotting. After Mtb infection, TNF-alpha and IL
      10 levels, alveolar macrophage apoptosis, and STAT3 and p-STAT3 expression
      increased significantly on days 1, 3, and 7 (P < 0.05), with maximum values on
      day 3. Furthermore, the Pearson correlation test showed that production of the
      cytokines TNF-alpha and IL-10 correlated strongly with expression of STAT3 and p
      STAT3 proteins (P < 0.05). Taken together, our results suggest that the STAT3
      signaling pathway might play a key role in the regulation of cell proliferation
      and alveolar macrophage apoptosis in response to Mtb. This provides a theoretical
      mechanism behind TB pathogenesis and host defense against Mtb, and contributes
      towards development of an effective treatment.

PMID- 27706767
TI  - Bioinformatic analyses of GRAS genes in Betula kirghisorum based on transcriptome
      data.
AB  - The transcriptomes of salt-stressed and unstressed Betula kirghisorum plants were
      analyzed using high throughput sequencing technology. A total of 52,239,804 and
      51,772,998 clean reads were obtained from the two libraries, respectively, and de
      novo assembled into 60,545 all-unigenes. A total of 39,997 unigenes were
      annotated using public databases. Overall, 7206 genes were differentially
      expressed in unigenes and were involved in 127 pathways. Thirteen transcription
      factor families were identified in B. kirghisorum, including GRAS proteins, which
      are plant-specific transcription factors. By using bioinformatic methods to
      predict and analyze physicochemical properties, structural data were obtained on
      the 19 potential GRAS proteins. The results revealed that these proteins are
      hydrophilic, with significant differences in their length and molecular weight.
      The main secondary structures were alpha helices and random coils. BkGRAS
      proteins possess typical GRAS domains: LHR I; VHIID motif; LHR II; PFYRE motif;
      and SAW motif. In the majority of BkGRAS proteins, AGG, AGA, UCU, GCU, GGG, CCA,
      GUU, GUG, AUU, GAU, and AAG codons were used preferentially. Aside from the
      BkGRAS17 gene (relative synonymous codon usage (RSCU) = 1.20), usage of the UUA
      codon by other BkGRAS genes was low (RSCU < 1.0). The effective number of codons
      showed that BkGRAS genes have low codon bias. Subcellular localization analysis
      that predicted these proteins are found in the nucleus, cytoplasm, or
      chloroplast. BkGRAS proteins were divided into six subfamilies: SCR, LISCL, SCL3,
      DELLA, HAM, and PAT1. These results provide important information for the further
      functional study of GRAS genes in B. kirghisorum.

PMID- 27706768
TI  - Effects of sacral nerve stimulation with acupuncture on gut transit time and c
      kit expression in colon of rats with slow transit constipation.
AB  - Sacral nerve stimulation (SNS) is an alternative surgical approach to alleviate
      fecal incontinence and constipation. This study aimed to explore the effects and
      underlying mechanisms of SNS with acupuncture on gut transit time and colon c-kit
      protein expression in rats with slow transit constipation (STC). Fifty Sprague
      Dawley rats were randomly divided into five groups: blank control, SNS,
      Mosapride, sham SNS, and STC model control group. The STC model was established
      by subcutaneous injection of morphine. Each group was treated over a 15-day
      period. Gut transit time was measured 1 day before the treatment started and
      after 5, 10, and 15 days of treatment. After the 15-day treatment, animals were
      sacrificed and colonic tissues were collected for analysis of c-kit protein
      expression, using western blot analysis. We found significant differences in gut
      transit time in the SNS group compared with the Mosapride group after 5 (P =
      0.001) and 10 (P = 0.004) days of treatment. After 15 days of treatment, there
      were no differences in gut transit time among the SNS, Mosapride, and blank
      control groups. However, significant differences were observed when comparing the
      SNS and Mosapride groups with the STC model and sham SNS groups. A decreased c
      kit protein expression was observed in the STC model control, sham SNS, and
      Mosapride groups, compared with the SNS group (P = 0.001). Our data indicate that
      SNS can decrease gut transit time and increase the expression of c-kit protein in
      rats with STC to improve colon transit function.

PMID- 27706769
TI  - Characterization of RsMYB28 and RsMYB29 transcription factor genes in radish
      (Raphanus sativus L.).
AB  - Glucosinolates (GSLs) are important secondary metabolites in Brassicaceae plants.
      Previous studies have mainly focused on GSL contents, types, and biosynthesis
      related genes, but the molecular characterization patterns of GSL biosynthesis
      related transcription factors remain largely unexplored in radish (Raphanus
      sativus L.). To isolate transcription factor genes regulating the GSL
      biosynthesis, genomic DNA and cDNA sequences of RsMYB28 and RsMYB29 genes were
      isolated in radish. Two R2R3-MYB domains were identified in the deduced amino
      acid sequences. Subcellular localization and yeast-one hybrid assays indicated
      that both the RsMYB28 and RsMYB29 genes were located in the nucleus and possessed
      transactivation activity. Reverse transcription quantitative analysis showed that
      the RsMYB28 and RsMYB29 genes were expressed in seeds, leaves, stems, and roots
      at the seedling, taproot thickening, and mature stages. Both genes were highly
      expressed during the seedling and taproot thickening stages. The expression level
      of RsMYB28 was found to be up-regulated following wounding, glucose, and abscisic
      acid treatments, whereas RsMYB29 was up-regulated following wounding and methyl
      jasmonate treatments. These results provide insights into the biological function
      and characterization of the RsMYB28 and RsMYB29 genes, and facilitate further
      dissection of the molecular regulatory mechanism underlying the GSL biosynthesis
      in radish.

PMID- 27706770
TI  - Activation of p38-mitogen-activated protein kinase contributes to ischemia
      reperfusion in rat brain.
AB  - Inflammation plays an important role in cerebral ischemia reperfusion, which can
      cause severe damage to the brain and may lead to cerebral hemorrhage
      transformation. p38-mitogen-activated protein kinase (p38mapk) has been
      implicated in the etiology of a number of diseases because it is a cause of
      inflammation, but comparatively little research has been carried out into its
      role in the etiology of ischemia reperfusion. We investigated the expression of
      p38mapk in cerebral ischemia reperfusion to gain a better understanding of its
      potential role in hemorrhagic transformation (HT). One hundred rats were randomly
      divided into three groups: an ischemia reperfusion group, an ischemia group, and
      a sham-operated group. We carried out neurological deficit assessments, infarct
      volume measurements, histopathological examinations, and immunohistochemistry
      analyses. p38mapk was overexpressed in the ischemia reperfusion group, which
      exhibited severe tissue damage and greater edema than the other two groups. These
      results suggest that p38mapk plays an important role in cerebral ischemia
      reperfusion, and may be one of the causes of HT.

PMID- 27706771
TI  - Detection of aneuploidies in spontaneous abortions by quantitative fluorescent
      PCR with short tandem repeat markers: a retrospective study.
AB  - Approximately 10-15% of all pregnancies end in spontaneous abortions. Many
      factors can lead to embryonic loss; however, it has been well established that
      over 50% of all miscarriages result from chromosomal abnormalities, primarily
      aneuploidies (>96%). Identifying the cause of miscarriage can significantly
      reduce the psychological stress in women, and enable better genetic counseling
      for a future pregnancy. Quantitative fluorescent polymerase chain reaction (QF
      PCR) has been previously used in the study of chromosomal abnormalities. In this
      retrospective study, the frequency of aneuploidy in samples of 130 miscarriages
      undergone by patients (age average: 34.1 +/- 4.6 years) at our institution was
      determined by QF-PCR using short tandem repeat markers. The gender of the
      miscarriage cases was determined by amplifying the amelogenin locus (70 males and
      60 females). Seventy-one of these cases (54.6%) presented aneuploidies such as
      trisomy, monosomy, triploidy, and double trisomy. Trisomy 22 was the most common
      aneuploidy (present in 14 cases), followed by trisomy 15, trisomy 16, and
      monosomy X. We also observed monosomy at chromosomes X and 21 and a case with
      multiple aneuploidies at chromosomes 16 and 22. The most common aneuploidies
      associated with miscarriages were detected by QF-PCR; therefore, we concluded
      that QF-PCR is a rapid and reliable method for the detection of aneuploidy, and
      can be used as an accessory to the widely used karyotype analysis.

PMID- 27706772
TI  - In silico identification and characterization of the WRKY gene superfamily in
      pepper (Capsicum annuum L.).
AB  - The WRKY family is one of the most important transcription factor families in
      plants, involved in the regulation of a broad range of biological roles. The
      recent releases of whole-genome sequences of pepper (Capsicum annuum L.) allow us
      to perform a genome-wide identification and characterization of the WRKY family.
      In this study, 61 CaWRKY proteins were identified in the pepper genome. Based on
      protein structural and phylogenetic analyses, these proteins were classified into
      four main groups (I, II, III, and NG), and Group II was further divided into five
      subgroups (IIa to IIe). Chromosome mapping analysis indicated that CaWRKY genes
      are distributed across all 12 chromosomes, although the location of four CaWRKYs
      (CaWRKY58-CaWRKY61) could not be identified. Two pairs of CaWRKYs located on
      chromosome 01 appear to be tandem duplications. Furthermore, the phylogenetic
      tree showed a close evolutionary relationship of WRKYs in three species from
      Solanaceae. In conclusion, this comprehensive analysis of CaWRKYs will provide
      rich resources for further functional studies in pepper.

PMID- 27706773
TI  - Relationship between genetic polymorphisms of methylenetetrahydrofolate reductase
      and breast cancer chemotherapy response.
AB  - Activity of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in
      folate metabolism, is influenced by mutations in the corresponding gene,
      contributing to a decrease in 5,10-MTHF. Due to such polymorphisms, individuals
      differ in MTHFR enzyme activity and plasma folate levels. We investigated the
      relationship between two common MTHFR polymorphisms (C677T and A1298C) and breast
      cancer (BC) chemotherapy response. From February 2013 to January 2016, 148
      advanced BC patients at the Center Hospital of Cangzhou were enrolled and treated
      with six different chemotherapy regimens. Subjects were genotyped using
      polymerase chain reaction-restriction fragment length polymorphism. Forty-one
      (27.7%), 70 (47.3%), and 37 (25.0%) patients carried the C/C, C/T, and T/T C677T
      genotypes, respectively; 101 (68.2%), 42 (28.4%), and 5 (3.4%) had the A/A, A/C,
      and C/C genotypes of A1298C, respectively. Total chemotherapy efficacy was 66.9%
      (99/148), with 7 (4.7%), 92 (62.2%), 36 (24.3%), and 13 (8.8%) cases showing
      complete response, partial response, no change, and progressive disease,
      respectively. Chemotherapy regimens did not differ in effectiveness (P > 0.05).
      Efficacy rates associated with C677T C/C, C/T, and T/T genotypes were 58.5, 58.6,
      and 91.9%, respectively, with T/T carriers exhibiting significantly better
      responses than the C/C (P < 0.05) and C/T groups (P < 0.05). Effectiveness among
      A1298C A/A, A/C, and C/C carriers was 70.6, 64.3, and 0.0%, respectively, but no
      difference was established between these genotypes in this regard (P > 0.05). The
      MTHFR C677T genotype may be associated with BC chemotherapy response, and could
      be of great value in guiding individualized treatment for this disease.

PMID- 27706774
TI  - Effect of miRNA-203 on cervical cancer cells and its underlying mechanism.
AB  - miRNA-203 is involved in the development and progression of various types of
      cancer. However, its role in cervical cancer remains unclear. The aim of this
      study was to investigate the effect of miRNA-203 on the proliferation and
      migration of HeLa cervical cancer cells, as well as survivin expression in these
      cells. A miRNA-203 primer probe was designed according to a sequence obtained
      from NCBI. The expression of miRNA-203 in cervical epithelial cells and cervical
      cancer cells was detected by quantitative reverse transcriptase-polymerase chain
      reaction. The miRNA-203 expression pattern was compared between these two cell
      lines. The cervical cancer cells were transfected with miRNA-203 mimic or
      inhibitor to determine their effects on proliferation and migration. The
      expression of the miRNA-203 target protein (survivin) was analyzed by western
      blot. Cervical cancer cells showed reduced miRNA-203 expression compared to
      cervical epithelial cells. Transfection of miRNA-203 mimic upregulated the
      expression of miRNA-203, suppressed cell proliferation and migration, and
      downregulated survivin expression (P < 0.05). However, downregulation of miRNA
      203 expression did not affect proliferation, migration, and survivin expression
      in cervical cancer cells (P > 0.05). In conclusion, upregulation of miRNA-203 in
      cervical cancer cells inhibits the proliferative and migratory capacities of
      these cells by downregulating the expression of survivin.

PMID- 27706775
TI  - Association of ADH1B Arg47His and ALDH2 Glu487Lys polymorphisms with risk of
      colorectal cancer and their interaction with environmental factors in a Chinese
      population.
AB  - Human colorectal cancer (CRC) is a major worldwide health concern, and its
      development has been shown to be associated with alcohol intake. We carried out a
      study to investigate the effect of the ADH1B Arg47His and ALDH2 Glu487Lys genetic
      polymorphisms and their interaction with alcohol consumption on development of
      CRC. Between March 2013 and May 2015, a total of 274 CRC patients and 358 healthy
      controls were recruited. Genotyping of sequence variations was performed using
      the polymerase chain reaction-restriction fragment length polymorphism method.
      Under a co-dominant model, individuals with the ADH1B Arg47His AA genotype showed
      increased CRC risk compared to those carrying the GG genotype, with an adjusted
      odds ratio (and 95% confidence interval) of 3.37 (2.00-5.70). Moreover, under
      dominant and recessive models, ADH1B Arg47His variant genotypes were associated
      with greater susceptibility to CRC when compared with the wild-type sequence.
      Both polymorphisms examined were positively associated with alcohol consumption
      in a Spearman correlation analysis of CRC risk. In conclusion, our study suggests
      that the ADH1B Arg47His polymorphism, but not the ALDH2 Glu487Lys variation, may
      influence development of CRC in the Chinese population.

PMID- 27706776
TI  - Development, characterization, and annotation of potential simple sequence
      repeats by transcriptome sequencing in pears (Pyrus pyrifolia Nakai).
AB  - Simple sequence repeats (SSRs), one of the most powerful molecular markers, can
      be used for DNA fingerprinting, variety identification, genetic mapping, and
      marker-assisted selection. Using the pear's (Pyrus pyrifolia Nakai) 75,764
      unigenes (55,676,271 bp) obtained by deep transcriptome sequencing, a total of
      10,622 novel SSRs were identified in 9154 unigenes, accounting for 14.02% of all
      unigenes. The average length and distribution of these SSRs was about 16 bp and
      5.24 kb, respectively. Dinucleotide repeat motifs were the main type, with a
      frequency of 55.87%, followed by trinucleotides (24.45%). There were 159 kinds of
      repeat motifs existing in the pear transcriptome. AG/CT was the most frequent
      motif, accounting for 49.64%. All 9154 SSR-containing unigenes were functionally
      annotated using Nr (NCBI non-redundant protein database), Nt (NCBI non-redundant
      nucleotide database), and the Swiss-Prot database, and were classified further by
      Gene Ontology and Clusters of Orthologous Groups. In addition, a total of 4300
      primer pairs were designed from all SSR loci obtained. Of these, 40 primers were
      randomly selected for PCR amplification and polyacrylamide gel (PAGE) analysis.
      Among the 40 primer pairs, 31 were successfully separated via PAGE. These
      findings also confirm that mining SSRs using next-generating sequencing
      technologies is a fast, effective, and reliable approach.

PMID- 27706777
TI  - Novel and highly informative Capsicum SSR markers and their cross-species
      transferability.
AB  - This study was undertaken primarily to develop new simple sequence repeat (SSR)
      markers for Capsicum. As part of this project aimed at broadening the use of
      molecular tools in Capsicum breeding, two genomic libraries enriched for AG/TC
      repeat sequences were constructed for Capsicum annuum. A total of 475 DNA clones
      were sequenced from both libraries and 144 SSR markers were tested on cultivated
      and wild species of Capsicum. Forty-five SSR markers were randomly selected to
      genotype a panel of 48 accessions of the Capsicum germplasm bank. The number of
      alleles per locus ranged from 2 to 11, with an average of 6 alleles. The
      polymorphism information content was on average 0.60, ranging from 0.20 to 0.83.
      The cross-species transferability to seven cultivated and wild Capsicum species
      was tested with a set of 91 SSR markers. We found that a high proportion of the
      loci produced amplicons in all species tested. C. frutescens had the highest
      number of transferable markers, whereas the wild species had the lowest. Our
      results indicate that the new markers can be readily used in genetic analyses of
      Capsicum.

PMID- 27706778
TI  - Prevalence of beta-lactamase classes A, C, and D among clinical isolates of
      Pseudomonas aeruginosa from a tertiary-level hospital in Bangkok, Thailand.
AB  - Pseudomonas aeruginosa is one of the most important causes of nosocomial
      infection and it has increasing resistance to many antimicrobial agents. beta
      lactamase production is the most frequent mechanism for beta-lactam resistance in
      P. aeruginosa. We evaluated the prevalence of beta-lactamase genes in P.
      aeruginosa for classes A, C, and D by polymerase chain reaction, and investigated
      clonal diversity by pulsed-field gel electrophoresis (PFGE). We used the disk
      diffusion method to test 118 non-duplicate clinical isolates of P. aeruginosa for
      antimicrobial susceptibility. We identified 51 isolates (43.22%) as multidrug
      resistant P. aeruginosa, approximately 44.91% of which were resistant to
      ceftazidime. beta-lactamase genes were found in 80 isolates of P. aeruginosa
      (67.80%). The genes that encode VEB-1, AmpC, and OXA-10 were detected in 9
      (7.62%), 75 (63.56%), and 18 (15.25%) of these isolates, respectively. The genes
      that encode PER-1, CTX-M, TEM-1 and derivatives, and SHV-1 were not found in any
      of the P. aeruginosa isolates. We identified 29 different pulsotypes by PFGE. Two
      predominant pulsotypes were found. In pulsotype 1, OXA- 10, which was co-produced
      with the AmpC gene, was predominant. Moreover, VEB-1-producing strains were found
      to be scattered in many pulsotypes, and AmpC-producing strains showed high
      pulsotype diversity. The prevalence of beta-lactamase genes in P. aeruginosa was
      represented by the genetic heterogeneity of OXA-10, AmpC, and VEB-1. The
      predominant clone of P. aeruginosa clinical isolates was OXA-10. This raises
      concern about oxacillinases among P. aeruginosa clinical isolates.

PMID- 27706779
TI  - Clinical significance of combined liver function and high-sensitivity C-reactive
      protein measurement in children with hand-foot-mouth disease.
AB  - Hand-foot-mouth disease (HFMD) is a common pediatric disease responsible for the
      development of rashes or herpes on the hand, foot, and mouth. Severe
      complications of HFMD include myocarditis, pulmonary edema, aseptic
      meningoencephalitis, and even death. Therefore, early diagnosis of HFMD is of
      particular importance. In this study, we determined the clinical value of the
      combined detection of liver function and high-sensitivity C-reactive protein (hs
      CRP) expression in children with HFMD. Three hundred children with HFMD were
      recruited to this study between July 2013 and July 2015 and divided into the mild
      and severe HFMD groups (N = 150 per group). The liver function [aspartate
      aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase
      (ALP) levels] and hs-CRP expression were evaluated using standardized tests, and
      the clinical value of combined detection of these indices (in parallel and
      serially) was determined. Patients in the severe HFMD group showed significantly
      higher levels of ALT, AST, ALP, and hs-CRP compared to those in the mild HFMD
      group (P < 0.05). The hs-CRP and liver function tests had low specificity and
      sensitivity, respectively. However, parallel combined detection improved the
      sensitivity and negative predicted value of these indices, whereas serial
      combined detection improved the specificity and positive predicted value. In
      conclusion, hs-CRP and liver function play a major role in the diagnosis of HFMD
      (and identifying its severity), and serial combined detection of these indices
      enhances the positive predicted value, and could be employed to diagnose severe
      HFMD at an earlier stage.

PMID- 27706781
TI  - Direct sequencing of mutations in the copper-transporting P-type adenosine
      triphosphate (ATP7B) gene for diagnosis and pathogenesis of Wilson's disease.
AB  - Copper-transporting P-type adenosine triphosphatase (ATP7B) has been identified
      as the pathogenic gene in hepatolenticular degeneration, or Wilson's disease
      (WD). The aim of this study was to explore the correlation between genetic
      mutations and the clinical profile of WD, and to discuss the value of mutation
      examination in its diagnosis for providing a scientific basis for the development
      of a method to examine genetic mutations. Sixty-eight Chinese Han patients with
      WD and 20 controls were included in this study. The ATP7B gene in DNA extracted
      from patient blood samples was amplified by PCR and sequenced. These sequences
      were compared against corresponding gene sequences obtained from healthy controls
      to statistically analyze the genetic mutations. Five of the nineteen mutations in
      ATP7B were newly detected mutations; moreover, 8 of these mutations were
      polymorphic (2 were newly identified). The Arg778Leu and Pro992Leu mutations in
      exons 8 and 13 were detected at the highest mutation frequencies of 25.74 and
      16.91%, respectively. The frequencies of all other mutations were below 5%.
      However, the clinical manifestations of WD did not differ significantly in
      patients with the Arg778Leu and Pro992Leu mutations. Therefore, these mutations
      were considered as hotspot mutations in Chinese WD patients. However, we observed
      no significant correlation between these genetic types and the clinical symptoms
      of WD. The correlation between the mutation genotype and disease phenotype
      remains to be elucidated. In conclusion, the highly sensitive and specific direct
      DNA sequencing method can be used to screen for the causative genes of WD.

PMID- 27706780
TI  - Clinical value of detection of immune index and inflammatory reaction changes in
      patients with autoimmune disease.
AB  - Previous studies have shown a close correlation between the generation of B cell
      autoantibodies and imbalances in T lymphocyte subpopulations and the occurrence
      of disease. In this study, we have analyzed the effects of abnormal expression of
      CD4+CD25+-regulatory T cells, T lymphocyte subpopulations, immunoglobulins,
      complement factors, inflammatory factors, and adhesion molecules in the
      peripheral blood on the occurrence and development of autoimmune disease. Eighty
      patients with autoimmune disease were randomly (equally) divided into active
      stage and stable-stage disease groups (according to pre-defined criteria). Fifty
      healthy people were recruited to the control group. The above-mentioned indices
      were detected by flow cytometry, immunity transmission turbidity, and enzyme
      linked immunosorbent assay. We observed an obvious decrease in the CD4+CD25+-
      regulatory T cell, CD4+ cell, CD4+/CD8+ cell, NK cell, C3, and C4 expression in
      all three groups; however, this decrease was statistically significant in the
      active-stage group (P < 0.05). Alternately, we observed a significant increase in
      the expression of CD8+ cells, immunoglobulin (Ig) A, IgG, IgM, tumor necrosis
      factor-alpha, interleukin (IL)-10, IL-17, interferon-g, intercellular adhesion
      molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in the
      active-stage group (P < 0.05). Therefore, inflammatory reactions and immune
      dysfunction occurs during the active-stage of autoimmune disease, and detection
      of the immune indices and inflammatory and adhesion factors could help evaluate
      the immune stage in these patients, providing an experimental basis for the
      determination of disease progression and clinical treatment.

PMID- 27706782
TI  - Selection of inbred maize (Zea mays L.) progenies by topcrosses conducted in
      contrasting environments.
AB  - The aim of this study was to identify inbred progenies of S0:1 maize (Zea mays
      L.) plants that were efficient at a low level of technology and responsive at a
      high level of technology through the use of topcrosses. Two contrasting
      environments were created using two levels of base fertilization and topdressing,
      so that the levels of nitrogen, phosphorus, and potassium were applied four times
      higher in one environment than in the other. We used S0:1 progenies derived from
      commercial hybrids in topcrosses with two testers (an elite line from the flint
      heterotic group and an elite line from the dent heterotic group). The progenies
      and three controls were evaluated in an augmented block design in Nossa Senhora
      das Dores, SE, Brazil in the 2010 crop season. The average grain yield in the
      high-technological level was 21.44% greater than that in the low-technological
      level. There were no changes in progeny behavior in the two technological levels
      for grain yield. The testers did not differ in the average grain yield of the
      progenies at the two technological levels. Therefore, it is possible to select
      progenies derived from commercial hybrids that have an efficient response to
      fertilization.

PMID- 27706783
TI  - Short Communication Quick method for identifying horse (Equus caballus) and
      donkey (Equus asinus) hybrids.
AB  - The domestication of the Equus genus 5000-6000 years ago has influenced the
      history of human civilization. As soon as horse and donkey species had been
      domesticated, they were crossbred, producing humanity's first documented attempt
      at animal genome manipulation. Since then, the mule (male donkey x female horse)
      and the reciprocal cross (the hinny, male horse x female donkey) have been the
      most common equine hybrids in the world. Due to their hybrid vigor, mules and
      hinnies have been intensively used for carrying loads and people and for tilling
      the land. Despite their importance, visual distinction of mules and hinnies is
      difficult due to high phenotypic resemblance. However, the distinction between
      these two hybrids is of pivotal importance for equid breeders and ranchers. In
      this study, an easy, low-cost, effective, and fast multiplex-polymerase chain
      reaction method was developed to distinguish the maternal origin of mules and
      hinnies, targeting the hyper-variable mitochondrial DNA D-loop region. This
      methodology can help breeders, ranchers, animal science professionals, and
      researchers manage their equine herds with more confidence and precision.

PMID- 27706784
TI  - Cloning and characterization of ChiMYB in Chrysanthemum indicum with an emphasis
      on salinity stress tolerance.
AB  - v-myb avianmyeloblastosis viral oncogene homolog (MYB) transcription factors are
      key regulators of stress responsive gene expression in plants. In this study, the
      MYB gene, ChiMYB (GenBank accession No. KT948997), was isolated from
      Chrysanthemum indicum, and was functionally characterized with an emphasis on
      salinity stress tolerance. The full ChiMYB cDNA sequence (948 bp) encoded a
      typical R2R3 MYB transcription factor that contained 315 amino acid residues and
      two MYB domains. The temporal expression pattern of ChiMYB was noted in C.
      indicum, and the highest level was detected in the roots, followed by leaves and
      stems. ChiMYB expression was induced by NaCl treatments, and transient expression
      of the fusion of ChiMYB and green fluorescent protein (GFP) indicated that the
      protein was targeted to the nuclei of onion epidermal cells. Arabidopsis plants
      overexpressing ChiMYB displayed improved tolerance to drought and salt stress.
      When under salt stress conditions, transgenic Arabidopsis plants had higher
      survival rates than non-transgenic wild-type plants. Chlorophyll content,
      intercellular CO2 concentration, photosynthetic rate, and stomatal conductance
      were higher in the transgenic Arabidopsis plants than in non-transgenic control
      plants. Further investigation revealed that ChiMYB was able to regulate the
      expression of RD29A, RAB18, COR15, ABI1, and ABA genes, which are involved in
      salt stress signaling pathways. Our findings demonstrated that ChiMYB is
      essential for plant responses to salt stress, and it may have great potential for
      the improvement of salt tolerance in crops.

PMID- 27706785
TI  - Enhancement of pectinase production by ultraviolet irradiation and diethyl
      sulfate mutagenesis of a Fusarium oxysporum isolate.
AB  - Fusarium oxysporum strain BM-201 was treated with ultraviolet (UV) radiation to
      obtain a high pectinase-producing strain. Mutant UV-10-41 was obtained and then
      treated by diethyl sulfate. Next, the mutant UV-diethyl sulfate-43 derived from
      UV-10-41 was selected as high pectinase-producing strain. Mutant UV-diethyl
      sulfate-43 was incubated on slant for 10 generations, demonstrating that the
      pectinase-producing genes were stable. Pectinase activity reached 391.2 U/mL,
      which is 73.6% higher than that of the original strain.

PMID- 27706786
TI  - Prominent contribution of Th1, Th17, and Tregs to the host response during M.
      neoaurum infection.
AB  - Nontuberculous mycobacteria are ubiquitous in outside environment and animals. As
      for nontuberculous mycobacteria infection, there is only limited information in
      humans regarding infection and the subsequent immune response, especially for
      Mycobacterium neoaurum. Here, haematoxylin-eosin and Ziehl-Neelsen staining were
      used to observe pathological changes and detect acid-fast bacilli in organ
      samples in mouse model. Flow cytometry and quantitative real-time polymerase
      chain reaction were performed to analyze the contribution of Th1, Th17 and Tregs
      to the host immune response. M. neoaurum caused chronic infection in mice,
      resulting in infiltrates with large aggregates of inflammatory cells, especially
      macrophages, in lung tissues. Our results indicated that 72% of CD4+ T cells
      appeared in the early days of infection, which was followed by a decrease to 47%
      by day 32, and then a rise to 76% by day 56. Moreover, we found higher frequency
      of IFN-g-producing CD4+ T cells and elevated mRNA expression of the transcription
      factor T-bet in the lungs; however, we observed lower mRNA expression of the
      transcription factor RORgt and lower frequency of IL-17-producing CD4+ T cells. A
      transient relative decrease in the number of Treg cells was observed in the
      lungs; however, the number of Tregs did not change significantly between the
      first and last day following infection. Thus, M. neoaurum causes chronic
      infection in C57BL/6 mice, with Th1, Th17, and Tregs playing a prominent role in
      the host response. The present study may lay the basis for further studies on the
      mechanisms underlying infection with nontuberculous mycobacteria.

PMID- 27706787
TI  - Effects of Varroa destructor on temperature and humidity conditions and
      expression of energy metabolism genes in infested honeybee colonies.
AB  - Varroa destructor mites pose an increasing global threat to the apicultural
      industry and agricultural ecology; however, the issue of whether certain
      environmental factors reflect the level of mite infection is far from resolved.
      Here, a wireless sensor network (WSN) system was used to examine how V.
      destructor, which has vital impacts on honeybee (Apis mellifera) health and
      survival, affects the temperature and humidity of honeybee hives in a field
      experiment. This approach may facilitate early identification of V. destructor in
      hives, and thus enable timely remedial action. Using quantitative PCR, we also
      evaluated the expression of two genes, adipokinetic hormone (AKH) and
      adipokinetic hormone receptor (AKHR).The results showed that temperature in
      highly infested broods was higher than that in broods with low infestation.
      Moreover, mite infection in honeybee colonies was positively correlated with
      temperature but negatively correlated with humidity (P < 0.05). Similar to
      previous observations, quantitative analysis suggested that the expression levels
      of AKH and AKHR from honeybees with low infection were significantly higher than
      those from bees with high infection (P < 0.01). These results showed that the
      expression levels of these genes in colonies with high mite infestation were
      closely associated with changes in hive temperature and humidity. This study
      demonstrates that Varroa infection not only causes changes in temperature inside
      honeybee colonies, but also affects the expression of honeybee energy metabolism
      genes.

PMID- 27706788
TI  - Synthesis and structure-activity relationship of oleanolic mono- or di-glycosides
      against Magnaporthe oryzae.
AB  - Saponins are naturally-occurring units with broad diversity and are usually
      recognized as phytoanticipins. In order to develop new saponin chemical entities
      with high activity against Magnaporthe oryzae, we selected oleanolic acid (OA),
      which has wide natural distribution and rich content in plants. We used the
      ability of OA to act as an aglycone for glycosylation to obtain information on
      the structure-activity relationship (SAR) for rational molecular pesticide
      design. Oleanolic mono- or di-glycosides were synthesized at either the C3
      hydroxy and/or C28-carboxyl position, using trichloroacetimidate or glycosyl
      bromide donors, respectively. Structures were confirmed by [1H]-,[13C]-NMR.
      Furthermore, the activity of the synthesized glycosides against M. oryzae was
      assessed in vitro, based on the mycelium growth rate. The twenty five oleanolic
      mono- or di-glycosides comprised fourteen saponins with 3-monosaccharide residue
      1a-1n, six saponins with 28-monosaccharide residue 2a-2f, and five saponins with
      3, 28-monosaccharide residue 3a-3e; all showed different activities against M.
      oryzae according to their different structures. We concluded that the optimal
      oleanolic mono- and di-glycoside structure for activity against M. oryzae is a C3
      connection of a hexose such as mannose, galactose, or glucose, in combination
      with a C28 connection to a small group such as allyl or a C3 connection to a
      pentose accompanied by a larger group such as another pentose or heptenyl at C28.

PMID- 27706789
TI  - Aquaporin 4 inhibition decreased synthesis of cytokines by acetazolamide in the
      hippocampus of rats with pentrazol-induced chronic epilepsy.
AB  - Epilepsy refers to a clinical syndrome generated by spontaneous seizures in the
      central nervous system. Epilepsy triggers a complex pathological process
      including inflammatory response and aquaporin 4 (AQP4) increase. It has been
      reported that AQP4 helps to enhance the immunological function of the central
      nervous system in pathological conditions, but the relationship between AQP4 and
      inflammatory cytokines is poorly understood in chronic epilepsy processes. As an
      inhibitor of sulfonamide carbonic anhydrase (CA), acetazolamide (AZA) may inhibit
      water infiltration through AQP4. In this context, pentylenetetrazole (PTZ) is
      used to induce the chronic epilepsy model in rats to study the chronic epilepsy
      effects of AQP4 inhibition on proinflammatory cytokine expression in the
      hippocampus and proinflammatory cytokine quantification analysis of the plasma.
      Based on the assumption that AQP4 regulates proinflammatory cytokine expression,
      this article aims to demonstrate this effect in chronic epilepsy of rats. Rats
      were divided into four groups and were treated with different drugs: saline
      (Control), acetazolamide (AZA), pentylenetetrazole (PTZ), and pentylenetetrazole
      plus acetazolamide (PTZ+AZA). The data showed that seizures increased
      proinflammatory cytokine expression and that AZA significantly inhibited AQP4
      expression. Overall, the results suggested that AQP4 inhibition could weaken
      excitotoxicity in epileptogenesis by reducing proinflammatory cytokines in the
      hippocampus. The findings provide a new insight into the involvement of cerebral
      edema insult and proinflammatory cytokines in the process of chronic epilepsy.

PMID- 27706790
TI  - Prediction of protein subcellular multisite localization using a new feature
      extraction method.
AB  - A basic problem of proteomics is identifying the subcellular locations of a
      protein. One factor making the problem more complicated is that some proteins may
      simultaneously exist in two or more than two subcellular locations. To improve
      multisite prediction quality, it is necessary to use effective feature extraction
      methods. Here, we developed a new feature extraction method based on the pK value
      and frequencies of amino acids to represent a protein as a real values vector.
      Using this novel feature extraction method, the multi-label k-nearest neighbors
      (ML-KNN) algorithm and setting different weights into different attributes' ML
      KNN, known as wML-KNN, were employed to predict multiplex protein subcellular
      locations. The best overall accuracy rate on dataset S1 from the predictor of
      Virus-mPLoc was 59.92 and 86.04% on dataset S2 from Gpos-mPLoc, respectively.

PMID- 27706791
TI  - Short Communication Microsatellite loci in the tetraploid spined loach, Cobitis
      biwae, and cross-species amplification in four related species.
AB  - Fifteen microsatellite loci were identified in the tetraploid spined loach,
      Cobitis biwae (Teleostei: Cobitidae). Among these, 14 were polymorphic (5-31
      alleles) and showed moderate to high cross-species amplification transferability
      in four related species, Cobitis matsubarai, Cobitis taenia, Misgurnus
      anguillicaudatus, and Misgurnus fossilis. The loci, described herein, will be
      useful for population genetics, phylogeny, parentage analysis, and detection of
      hybridization among Cobitis species.

PMID- 27706792
TI  - RETRACTION of articles with plagiarism in common with other publications.
AB  - The GMR editorial staff was alerted about some manuscripts that were found to be
      substantially equal. The Publisher and Editor decided to retract these articles
      in accordance with the recommendations of the Committee on Publication Ethics
      (COPE). After a thorough investigation, we have strong reason to believe that the
      peer review process was failure and, after review and contacting the authors, the
      editors of Genetics and Molecular Research decided to retract these articles. The
      authors and their institutions were advised of this serious breach of ethics. The
      articles containing plagiarism in common with other publications are: Peng ZA, Lu
      RB, Xiao DM and Xiao ZM (2016). Increased expression of the lncRNA BANCR and its
      prognostic significance in human osteosarcoma. Genet. Mol. Res. 15 (1):
      gmr15017480 - DOI: 10.4238/gmr.15017480. Man HB, Bi WP and Man HH (2016).
      Decreased microRNA-198 expression and its prognostic significance in human
      glioma. Genet. Mol. Res. 15 (2): gmr.15027656 - DOI: 10.4238/gmr.15027656. Tang
      T, Zhang GC, Li CF, Liu YF, et al. (2016). Decreased miR-452 expression in human
      colorectal cancer and its tumor suppressive function. Genet. Mol. Res. 15 (2):
      gmr.15027730 - DOI: 10.4238/gmr.15027730. Ma YB, Song DW, Nie RH and Mu GY
      (2016). MicroRNA-32 functions as a tumor suppressor and directly targets EZH2 in
      uveal melanoma. Genet. Mol. Res. 15 (2): gmr.15027935 - DOI:
      10.4238/gmr.15027935. Wang XJ, Xia M and Bi WP (2016). Decreased expression of
      miR-874 and its tumor suppressive function in human colorectal cancer. Genet.
      Mol. Res. 15 (2): gmr.15028077 - DOI: 10.4238/gmr.15028077. Zhuo HC, Song YF, Ye
      J, Lai GX, et al. (2016). MicroRNA-154 functions as a tumor suppressor and
      directly targets HMGA2 in human non-small cell lung cancer. Genet. Mol. Res. 15
      (2): gmr.15028173 - DOI: 10.4238/gmr.15028173.

PMID- 27706793
TI  - Detection of quantitative trait loci for kernel oil and protein concentration in
      a B73 and Zheng58 maize cross.
AB  - Maize (Zea mays L.) is one of the most important food crops throughout the world,
      and provides oil and proteins to humans and livestock. Kernel oil and protein
      content in maize are two complex quantitative traits. In order to identify
      quantitative trait loci (QTL) controlling oil and protein concentration in maize
      kernels, and to evaluate their genetic effects, QTL analysis was conducted on an
      F3:4 population derived from a cross between an inbred line with a low oil and
      protein concentration (Zheng58) and an inbred line with a higher oil and protein
      concentration (B73). A total of 189 polymorphic simple sequence repeat markers
      were used to construct a linkage map. Eleven QTLs for kernel oil concentration
      were detected on nine chromosomes, except for chromosome 9. A single QTL
      explained 4.6 to 11.1% of the phenotypic variance. Ten QTLs for kernel protein
      concentration were also detected on nine chromosomes, except for chromosome 9. A
      single QTL explained 4.2 to 11.4% of the phenotypic variance. Interestingly,
      novel QTLs for oil concentration (qOIL08-01 and qOIL10-01) and QTLs for protein
      concentration (qPRO01-01 and qPRO05-01) were specific to the population studied,
      which could explain 7.1 to 11.1% of the phenotypic variance. These results will
      provide better understanding of the genetic basis of oil and protein
      concentrations in maize. The markers closely linked with the QTLs will facilitate
      breeding of maize varieties with high oil and protein concentrations through
      molecular marker-assisted selection.

PMID- 27706794
TI  - Population genetic diversity and genetic structure of Spodoptera exigua around
      the Bohai Gulf area of China based on mitochondrial DNA signatures.
AB  - The beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae), is an economically
      important pest that causes major losses in some main crop-producing areas of
      China. To control this pest effectively, it is necessary to investigate its
      population genetic diversity and genetic structure around the Bohai Gulf area of
      China. In this study, we used two mitochondrial genes, COI (578 bp) and Cytb (724
      bp), to investigate its genetic diversity. We obtained 622 COI sequences and 462
      Cytb sequences from 23 populations, and 28 and 73 haplotypes, respectively, were
      identified. Low to moderate levels of genetic diversity (COI: Hd = 0.267 +/-
      0.023, Pi = 0.00082 +/- 0.00010; Cytb: Hd = 0.689 +/- 0.018, Pi = 0.00255 +/-
      0.00029) for the total populations were observed. Phylogenetic and median-joining
      network analyses indicated no distinct geographical distribution pattern among
      the haplotypes. Overall, this study revealed that there was significant
      differentiation among the populations (COI: FST = 0.158, P < 0.001; Cytb: FST =
      0.148, P < 0.001). FST values for Shenyang, Baoding, and Funing were
      significantly different to those for most of the other populations. Finally,
      unimodal mismatch distribution analysis, combined with negative neutrality test
      results, showed a recent population expansion of the beet armyworm around the
      Bohai Gulf area of China.

PMID- 27706795
TI  - Understanding cutaneous tuberculosis in children.

PMID- 27706796
TI  - Sirolimus is highly effective for lymph leakage in microcystic lymphatic
      malformations with skin involvement.

PMID- 27706797
TI  - Repurposing Drugs for Cognition in Schizophrenia.
AB  - Currently approved treatments for schizophrenia only minimally affect the
      cognitive features of the illness that are the most closely related to
      disability. Hence, there is now considerable effort to repurpose drugs for
      schizophrenia, and to seek agents that can improve cognition by targeting
      receptor systems other than the dopaminergic system. The results of these studies
      have been mixed thus far; however, this continues to be a high-priority area of
      schizophrenia research and an important unmet need.

PMID- 27706798
TI  - Evidence of NI-0101 pharmacological activity, an anti-TLR4 antibody, in a
      randomized phase I dose escalation study in healthy volunteers receiving LPS.
AB  - Toll-like receptor-4 (TLR4) pathways are major contributors to pathological
      inflammatory responses induced by tissue damage. NI-0101 is the first monoclonal
      antibody (mAb) blocking TLR4 signaling. This activity is independent of the
      ligand type and concentration, therefore, potentially blocking any TLR4 ligands.
      A phase I single ascending dose study was conducted in 73 healthy volunteers to
      evaluate NI-0101 tolerability, preliminary safety, pharmacokinetics (PKs), and
      pharmacodynamics (PDs), in absence and in presence of a systemic challenge with
      lipopolysaccharide (LPS), a TLR4 ligand. NI-0101 was well tolerated without
      safety concern. The PK profile was characterized by a half-life of ~10 days at
      high concentrations and by a rapid elimination at low concentrations due to
      expected target-mediated drug disposition. NI-0101 prevented cytokine release
      following ex vivo and in vivo LPS administration and prevented the C-reactive
      protein (CRP) increase and the occurrence of flu-like symptoms expected following
      the in vivo administration of LPS.

PMID- 27706799
TI  - Survival model construction guided by fit and predictive strength.
AB  - Survival model construction can be guided by goodness-of-fit techniques as well
      as measures of predictive strength. Here, we aim to bring together these distinct
      techniques within the context of a single framework. The goal is how to best
      characterize and code the effects of the variables, in particular time
      dependencies, when taken either singly or in combination with other related
      covariates. Simple graphical techniques can provide an immediate visual
      indication as to the goodness-of-fit but, in cases of departure from model
      assumptions, will point in the direction of a more involved and richer
      alternative model. These techniques appear to be intuitive. This intuition is
      backed up by formal theorems that underlie the process of building richer models
      from simpler ones. Measures of predictive strength are used in conjunction with
      these goodness-of-fit techniques and, again, formal theorems show that these
      measures can be used to help identify models closest to the unknown non
      proportional hazards mechanism that we can suppose generates the observations.
      Illustrations from studies in breast cancer show how these tools can be of help
      in guiding the practical problem of efficient model construction for survival
      data.

PMID- 27706800
TI  - Development and validation of algorithms for the detection of statin myopathy
      signals from electronic medical records.
AB  - The purpose of this study was to develop and validate sensitive algorithms to
      detect hospitalized statin-induced myopathy (SIM) cases from electronic medical
      records (EMRs). We developed four algorithms on a training set of 31,211 patient
      records from a large tertiary hospital. We determined the performance of these
      algorithms against manually curated records. The best algorithm used a
      combination of elevated creatine kinase (>4* the upper limit of normal (ULN)),
      discharge summary, diagnosis, and absence of statin in discharge medications.
      This algorithm achieved a positive predictive value of 52-71% and a sensitivity
      of 72-78% on two validation sets of >30,000 records each. Using this algorithm,
      the incidence of SIM was estimated at 0.18%. This algorithm captured three times
      more rhabdomyolysis cases than spontaneous reports (95% vs. 30% of manually
      curated gold standard cases). Our results show the potential power of utilizing
      data and text mining of EMRs to enhance pharmacovigilance activities.

PMID- 27706801
TI  - Collision-induced thermochemistry of reactions of dissociation of glycyl
      homopeptides-An experimental and theoretical analysis.
AB  - The research draws on experimental and theoretical data about energetics and
      kinetics of mass spectrometric (MS) reactions of glycyl homopenta- (G5) and
      glycyl homohexapeptides (G6). It shows the great applicability of the methods of
      quantum chemistry to predict MS profile of peptides using energetics of collision
      induced dissociation (CID) fragment species. Mass spectrometry is among
      irreplaceable methods, providing unambiguous qualitative, quantitative and
      structural information about analytes, applicable to many scientific areas like
      environmental chemistry; food chemistry; medicinal chemistry; and more. Our study
      could be considered of substantial interdisciplinary significance, where MS
      proteomics is widely used. The experimental design involves electrospray
      ionization (ESI) and CID MS/MS. Theoretical design is based on ab initio and
      density functional theory (DFT) methods. Experimental MS and theoretical free
      Gibbs energies as well as rate constants of fragment reactions are compared. The
      thermodynamic encompasses gas-phase and polar continuum analysis, including polar
      protic and aprotic solvents within temperature T = 10-500 K; dielectric constant
      epsilon = 0-78, pH, and ionic strengths MU = 0.001-1.0 mol dm-1 . There are
      computed and discussed 39 protonated forms of peptides at amide N- and -(NHC)=O
      centers; corresponding fragment ions studying their thermodynamic stability
      depending on experimental conditions. A correlation analysis between molecular
      conformations of parent ions and fragment species; their proton accepting ability
      and internal energy distribution is carried out. Data about ionization potentials
      (IPs) and electron affinities (EAs) are discussed, as well.

PMID- 27706802
TI  - Invasive Management for Elderly Adults with Acute Coronary Syndrome: Where Are We
      Now?

PMID- 27706803
TI  - Systematic review of active surveillance versus surgical management of
      asymptomatic small non-functioning pancreatic neuroendocrine neoplasms.
AB  - BACKGROUND: The incidence of asymptomatic, sporadic, small non-functioning
      pancreatic neuroendocrine neoplasms (NF-PNENs) has increased in recent decades.
      Conservative treatment has been advocated for these tumours. The aim of this
      study was systematically to evaluate the literature on active surveillance and to
      compare this with surgical management for asymptomatic sporadic small NF-PNENs.
      METHODS: PubMed, Embase and the Cochrane Library were searched systematically for
      studies that compared the active surveillance of asymptomatic, sporadic, small NF
      PNENs with surgical management. PRISMA guidelines for systematic reviews were
      followed. RESULTS: After screening 3915 records, five retrospective studies with
      a total of 540 patients were included. Of these, 327 patients (60.6 per cent)
      underwent active surveillance and 213 (39.4 per cent) had surgery. There was wide
      variation in the tumour diameter threshold considered as inclusion criterion (2
      cm to any size). The median length of follow-up ranged from 28 to 45 months.
      Measurable tumour growth was observed in 0-51.0 per cent of patients. Overall, 46
      patients (14.1 per cent) underwent pancreatic resection after initial
      conservative treatment. In most patients the reason was an increase in tumour
      size (19 of 46). There were no disease-related deaths in the active surveillance
      group in any of the studies. CONCLUSION: This systematic review suggests that
      active surveillance of patients affected by sporadic, small, asymptomatic NF
      PNENs may be a good alternative to surgical treatment.

PMID- 27706804
TI  - Bisphosphonates for steroid-induced osteoporosis.
AB  - BACKGROUND: This is an update of a Cochrane Review first published in 1999.
      Corticosteroids are widely used in inflammatory conditions as an
      immunosuppressive agent. Bone loss is a serious side effect of this therapy.
      Several studies have examined the use of bisphosphonates in the prevention and
      treatment of glucocorticosteroid-induced osteoporosis (GIOP) and have reported
      varying magnitudes of effect. OBJECTIVES: To assess the benefits and harms of
      bisphosphonates for the prevention and treatment of GIOP in adults. SEARCH
      METHODS: We searched CENTRAL, MEDLINE and Embase up to April 2016 and
      International Pharmaceutical Abstracts (IPA) via OVID up to January 2012 for
      relevant articles and conference proceedings with no language restrictions. We
      searched two clinical trial registries for ongoing and recently completed studies
      (ClinicalTrials.gov and the World Health Organization (WHO) International
      Clinical Trials Registry Platform (ICTRP) search portal). We also reviewed
      reference lists of relevant review articles. SELECTION CRITERIA: We included
      randomised controlled trials (RCTs) satisfying the following criteria: 1)
      prevention or treatment of GIOP; 2) adults taking a mean steroid dose of 5.0
      mg/day or more; 3) active treatment including bisphosphonates of any type alone
      or in combination with calcium or vitamin D; 4) comparator treatment including a
      control of calcium or vitamin D, or both, alone or with placebo; and 4) reporting
      relevant outcomes. We excluded trials that included people with transplant
      associated steroid use. DATA COLLECTION AND ANALYSIS: At least two review authors
      independently selected trials for inclusion, extracted data, performed 'risk of
      bias' assessment and evaluated the certainty of evidence using the GRADE
      approach. Major outcomes of interest were the incidence of vertebral and
      nonvertebral fractures after 12 to 24 months; the change in bone mineral density
      (BMD) at the lumbar spine and femoral neck after 12 months; serious adverse
      events; withdrawals due to adverse events; and quality of life. We used standard
      Cochrane methodological procedures. MAIN RESULTS: We included a total of 27 RCTs
      with 3075 participants in the review. Pooled analysis for incident vertebral
      fractures included 12 trials (1343 participants) with high-certainty evidence and
      low risk of bias. In this analysis 46/597 (or 77 per 1000) people experienced new
      vertebral fractures in the control group compared with 31/746 (or 44 per 1000;
      range 27 to 70) in the bisphosphonate group; relative improvement of 43% (9% to
      65% better) with bisphosphonates; absolute increased benefit of 2% fewer people
      sustaining fractures with bisphosphonates (5% fewer to 1% more); number needed to
      treat for an additional beneficial outcome (NNTB) was 31 (20 to 145) meaning that
      approximately 31 people would need to be treated with bisphosphonates to prevent
      new vertebral fractures in one person.Pooled analysis for incident nonvertebral
      fractures included nine trials with 1245 participants with low-certainty evidence
      (downgraded for imprecision and serious risk of bias as a patient-reported
      outcome). In this analysis 30/546 (or 55 per 1000) people experienced new
      nonvertebral fracture in the control group compared with 29/699 (or 42 per 1000;
      range 25 to 69) in the bisphosphonate group; relative improvement of 21% with
      bisphosphonates (33% worse to 53% better); absolute increased benefit of 1% fewer
      people with fractures with bisphosphonates (4% fewer to 1% more).Pooled analysis
      on BMD change at the lumbar spine after 12 months included 23 trials with 2042
      patients. Eighteen trials with 1665 participants were included in the pooled
      analysis on BMD at the femoral neck after 12 months. Evidence for both outcomes
      was moderate-certainty (downgraded for indirectness as a surrogate marker for
      osteoporosis) with low risk of bias. Overall, the bisphosphonate groups reported
      stabilisation or increase in BMD, while the control groups showed decreased BMD
      over the study period. At the lumbar spine, there was an absolute increase in BMD
      of 3.5% with bisphosphonates (2.90% to 4.10% higher) with a relative improvement
      of 1.10% with bisphosphonates (0.91% to 1.29%); NNTB 3 (2 to 3). At the femoral
      neck, the absolute difference in BMD was 2.06% higher in the bisphosphonate group
      compared to the control group (1.45% to 2.68% higher) with a relative improvement
      of 1.29% (0.91% to 1.69%); NNTB 5 (4 to 7).Pooled analysis on serious adverse
      events included 15 trials (1703 participants) with low-certainty evidence
      (downgraded for imprecision and risk of bias). In this analysis 131/811 (or 162
      per 1000) people experienced serious adverse events in the control group compared
      to 136/892 (or 147 per 1000; range 120 to 181) in the bisphosphonate group;
      absolute increased harm of 0% more serious adverse events (2% fewer to 2% more);
      a relative per cent change with 9% improvement (12% worse to 26% better).Pooled
      analysis for withdrawals due to adverse events included 15 trials (1790 patients)
      with low-certainty evidence (downgraded for imprecision and risk of bias). In
      this analysis 63/866 (or 73 per 1000) people withdrew in the control group
      compared to 76/924 (or 77 per 1000; range 56 to 107) in the bisphosphonate group;
      an absolute increased harm of 1% more withdrawals with bisphosphonates (95% CI 1%
      fewer to 3% more); a relative per cent change 6% worse (95% CI 47% worse to 23%
      better).Quality of life was not assessed in any of the trials. AUTHORS'
      CONCLUSIONS: There was high-certainty evidence that bisphosphonates are
      beneficial in reducing the risk of vertebral fractures with data extending to 24
      months of use. There was low-certainty evidence that bisphosphonates may make
      little or no difference in preventing nonvertebral fractures. There was moderate
      certainty evidence that bisphosphonates are beneficial in preventing and treating
      corticosteroid-induced bone loss at both the lumbar spine and femoral neck.
      Regarding harm, there was low-certainty evidence that bisphosphonates may make
      little or no difference in the occurrence of serious adverse events or
      withdrawals due to adverse events. We are cautious in interpreting these data as
      markers for harm and tolerability due to the potential for bias.Overall, our
      review supports the use of bisphosphonates to reduce the risk of vertebral
      fractures and the prevention and treatment of steroid-induced bone loss.

PMID- 27706805
TI  - Bowel function and quality of life after local excision or total mesorectal
      excision following chemoradiotherapy for rectal cancer.
AB  - BACKGROUND: Local excision for rectal cancer is expected to offer a better
      functional outcome than conventional surgery. The aim of the present study was to
      compare quality of life and bowel function in patients with rectal cancer who
      underwent either local excision or conventional surgery after chemoradiotherapy.
      METHODS: This was a retrospective multicentre study. Patients who underwent local
      excision were compared with those who had mesorectal excision. Quality of life
      and bowel function were investigated using validated questionnaires (European
      Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29
      and Memorial Sloan-Kettering Cancer Center Bowel Function Instrument) at a median
      follow-up of 49 (range 13-95) months. Further analysis was undertaken of data
      from patients who underwent local excision alone compared with those requiring
      subsequent radical surgery. Statistical significance was set at P < 0.010.
      RESULTS: The mean constipation score was significantly better in the local
      excision group than in the mesorectal excision group (3.8 (95 per cent c.i. 0.3
      to 7.2) versus 19.8 (12.1 to 27.4); P < 0.001). Compared with patients who
      underwent mesorectal excision, those who had local excision had less sensation of
      incomplete emptying (mean score 3.7 (3.4 to 4.0) versus 2.8 (2.5 to 3.1); P <
      0.001) and second bowel movements within 15 min (mean score 3.6 (3.3 to 3.9)
      versus 3.0 (2.7 to 3.3); P = 0.006). Patients who underwent local excision alone
      scored better than those who had mesorectal excision, particularly for bowel
      function, who, in turn, scored better than patients requiring subsequent radical
      surgery following local excision. CONCLUSION: Patients who underwent local
      excision had a better quality of life and bowel function than those who underwent
      mesorectal excision.

PMID- 27706806
TI  - The Mind Bending Quest for Cognitive Enhancers.
AB  - Adequate cognitive functioning is essential for daily activities. When there is
      an insult to the brain, cognitive abilities can suffer, which, in turn, produce
      substantial medical and functional impairment. Advances in neurobiology, circuit
      neuroscience, and clinical assessment technology are converging in a manner that
      holds promise for the development of new pharmacological agents for cognitive
      enhancement in neuropsychiatric disease.

PMID- 27706807
TI  - Intermediate monocytes are increased in enthesitis-related arthritis, a category
      of juvenile idiopathic arthritis.
AB  - Microarray of peripheral blood (PB) and synovial fluid mononuclear cells (PBMC,
      SFMC) of patients with juvenile idiopathic arthritis-enthesitis-related arthritis
      (JIA-ERA) has shown the involvement of monocytes. On the basis of CD14 and CD16
      expression, monocytes are classified as classical, intermediate and non
      classical. In response to Toll-like receptor (TLR) stimulation, intermediate
      monocytes produce proinflammatory cytokines and play a role in inflammatory
      diseases. Therefore, we have studied the microarray profile of monocytes, the
      frequency of their subsets and cytokine production. Monocyte-specific microarray
      analysis was performed in six healthy controls' PBMC and six patients' PBMC and
      SFMC using Illumina chips WG12. Monocyte subsets were assessed in 46 patients
      with JIA-ERA and 17 healthy controls and 17 disease controls by flow cytometry.
      Interleukin (IL)-23 and tumour necrosis factor (TNF) levels were measured in
      culture supernatants of eight controls and seven patients' PBMC/SFMC with/without
      lipopolysaccharide (LPS) stimulation. Cytokine-producing intermediate monocytes
      were assessed by flow cytometry. Genes related to antigen presentation, cytokine
      signalling and TLR pathway were regulated differentially in PB and synovial
      monocytes of patients with JIA-ERA. Key genes of intermediate monocytes, such as
      CLEC10A and MARCO, were expressed three- to fourfold more in JIA-ERA. In PB, the
      frequency of intermediate monocytes was significantly higher in JIA-ERA (4.90% +/
      3.5) compared to controls (1.8% +/- 1.06; P < 0.001). Patients' synovial cells
      also had more intermediate monocytes compared to PB (11.25% +/- 11.32, 5.9% +/-
      4.8; P = 0.004). Intermediate monocytes are the major producers of IL-23. Thus,
      intermediate monocytes may play an important role in JIA-ERA, possibly by
      producing cytokines, and contribute to joint inflammation.

PMID- 27706809
TI  - Analytical Characterization of Polyphenols from Tara and Caesalpinia decapetala
      as Stabilizers of O/W Emulsions.
AB  - The extracts (0.5% [w/w]) from Caesalpinia spinosa or tara (CS) and Caesalpinia
      decapetala (CD) leaves were evaluated for their ability to inhibit lipid
      oxidation using oil-in-water (O/W) emulsions as the model system. Liquid
      chromatography (LC) combined with mass spectrometry (MS), using a hybrid
      quadrupole time-of-flight (QTOF) mass spectrometer, was employed for (1) the
      identification of potential antioxidant species in the extracts and (2) to follow
      their evolution through aging of the emulsions. CS extracts, containing esters
      and conjugated forms of gallic acid (GA), turned out to be more effective than
      CD, rich in flavonoid species, in stabilizing the O/W emulsions. After 3 wk at 33
      degrees C, peroxide values of emulsions stabilized with CS and CD extracts were
      6.7 and 18.2 meq hydroperoxides/kg, respectively. Responses measured for the
      oligomers and esterified forms of GA in CS containing emulsions decreased with
      time; however, the response for the free form of GA kept increasing.

PMID- 27706810
TI  - Antitumor effects of 4-methylumbelliferone, a hyaluronan synthesis inhibitor, on
      malignant peripheral nerve sheath tumor.
AB  - Hyaluronan (HA) has been shown to play important roles in the growth, invasion
      and metastasis of malignant tumors. Our previous study showing that high HA
      expression in malignant peripheral nerve sheath tumors (MPNST) is predictive of
      poor patient prognosis, prompted us to speculate that inhibition of HA synthesis
      in MPNST might suppress the tumorigenicity. The aim of our study was to
      investigate the antitumor effects of 4-methylumbelliferone (MU), an HA synthesis
      inhibitor, on human MPNST cells and tissues. The effects of MU on HA accumulation
      and tumorigenicity in MPNST cells were analyzed in the presence or absence of MU
      in an in vitro as well as in vivo xenograft model using human MPNST cell lines,
      sNF96.2 (primary recurrent) and sNF02.2 (metastatic). MU significantly inhibited
      cell proliferation, migration and invasion in both MPNST cell lines. HA binding
      protein (HABP) staining, particle exclusion assay and quantification of HA
      revealed that MU significantly decreased HA accumulation in the cytoplasms and
      pericellular matrices in both MPNST cell lines. The expression levels of HA
      synthase2 (HAS2) and HA synthase3 (HAS3) mRNA were downregulated after treatment
      with MU. MU induced apoptosis of sNF96.2 cells, but not sNF02.2 cells. MU
      administration significantly inhibited the tumor growth of sNF96.2 cells in the
      mouse xenograft model. To the best of our knowledge, our study demonstrates for
      the first time the antitumor effects of MU on human MPNST mediated by inhibition
      of HA synthesis. Our results suggest that MU may be a promising agent with novel
      antitumor mechanisms for MPNST.

PMID- 27706808
TI  - Understanding the regulation of pattern recognition receptors in inflammatory
      diseases - a 'Nod' in the right direction.
AB  - Nucleotide-binding oligomerization domain (NOD) -like receptors (NLRs) are a
      family of 23 receptors known as pattern recognition receptors; they are expressed
      in many cell types and play a key role in the innate immune response. The NLRs
      are activated by pathogen-associated molecular patterns, which include
      structurally conserved molecules present on the surfaces of bacteria. The
      activation of these NLRs by pathogens results in the downstream activation of
      signalling kinases and transcription factors, culminating in the transcription of
      genes coding for pro-inflammatory factors. Expression of NLR is altered in many
      cellular, physiological and disease states. There is a lack of understanding of
      the mechanisms by which NLR expression is regulated, particularly in chronic
      inflammatory states. Genetic polymorphisms and protein interactions are included
      in such mechanisms. This review seeks to examine the current knowledge regarding
      the regulation of this family of receptors and their signalling pathways as well
      as how their expression changes in disease states with particular focus on NOD1
      and NOD2 in inflammatory bowel diseases among others.

PMID- 27706812
TI  - Multimodel Validity Assessment of Groundwater Flow Simulation Models Using Area
      Metric Approach.
AB  - We demonstrate the application of the Area Metric developed by Ferson et al.
      (2008) for multimodel validity assessment. The Area Metric quantified the degree
      of models' replicative validity: the degree of agreement between the observed
      data and the corresponding simulated outputs represented as their empirical
      cumulative distribution functions (ECDFs). This approach was used to rank
      multiple representations of a case study groundwater flow model of a landfill by
      their Area Metric scores. A multimodel approach allows to account for
      uncertainties that may either be epistemic (from lack of knowledge) or aleatory
      (from variability inherent in the system). The Area Metric approach enables
      explicit incorporation of model uncertainties, epistemic as well as aleatory,
      into validation assessment. The proposed approach informs understanding of the
      collected data and that of the model domain. It avoids model overfitting to a
      particular system state, and in fact is a blind assessment of the models'
      validity: models are not adjusted, or updated, to achieve a better numerical fit.
      This approach assesses the degree of models' validity, in place of the typical
      binary model validation/invalidation process. Collectively, this increases
      confidence in the model's representativeness that, in turn, reduces risk to model
      users.

PMID- 27706811
TI  - Oncogenic targets Mmp7, S100a9, Nppb and Aldh1a3 from transcriptome profiling of
      FAP and Pirc adenomas are downregulated in response to tumor suppression by
      Clotam.
AB  - Intervention strategies in familial adenomatous polyposis (FAP) patients and
      other high-risk colorectal cancer (CRC) populations have highlighted a critical
      need for endoscopy combined with safe and effective preventive agents. We
      performed transcriptome profiling of colorectal adenomas from FAP patients and
      the polyposis in rat colon (Pirc) preclinical model, and prioritized molecular
      targets for prevention studies in vivo. At clinically relevant doses in the Pirc
      model, the drug Clotam (tolfenamic acid, TA) was highly effective at suppressing
      tumorigenesis both in the colon and in the small intestine, when administered
      alone or in combination with Sulindac. Cell proliferation in the colonic crypts
      was reduced significantly by TA, coincident with increased cleaved caspase-3 and
      decreased Survivin, beta-catenin, cyclin D1 and matrix metalloproteinase 7. From
      the list of differentially expressed genes prioritized by transcriptome
      profiling, Mmp7, S100a9, Nppb and Aldh1a3 were defined as key oncogene candidates
      downregulated in colon tumors after TA treatment. Monthly colonoscopies revealed
      the rapid onset of tumor suppression by TA in the Pirc model, and the temporal
      changes in Mmp7, S100a9, Nppb and Aldh1a3, highlighting their value as potential
      early biomarkers for prevention in the clinical setting. We conclude that TA, an
      "old drug" repurposed from migraine, offers an exciting new therapeutic avenue in
      FAP and other high-risk CRC patient populations.

PMID- 27706813
TI  - Optimization of Vacuum Impregnation with Calcium Lactate of Minimally Processed
      Melon and Shelf-Life Study in Real Storage Conditions.
AB  - Vacuum impregnation (VI) is a processing operation that permits the impregnation
      of fruit and vegetable porous tissues with a fast and more homogeneous
      penetration of active compounds compared to the classical diffusion processes.
      The objective of this research was to investigate the impact on VI treatment with
      the addition of calcium lactate on qualitative parameters of minimally processed
      melon during storage. For this aim, this work was divided in 2 parts. Initially,
      the optimization of process parameters was carried out in order to choose the
      optimal VI conditions for improving texture characteristics of minimally
      processed melon that were then used to impregnate melons for a shelf-life study
      in real storage conditions. On the basis of a 23 factorial design, the effect of
      Calcium lactate (CaLac) concentration between 0% and 5% and of minimum pressure
      (P) between 20 and 60 MPa were evaluated on color and texture. Processing
      parameters corresponding to 5% CaLac concentration and 60 MPa of minimum pressure
      were chosen for the storage study, during which the modifications of main
      qualitative parameters were evaluated. Despite of the high variability of the raw
      material, results showed that VI allowed a better maintenance of texture during
      storage. Nevertheless, other quality traits were negatively affected by the
      application of vacuum. Impregnated products showed a darker and more translucent
      appearance on the account of the alteration of the structural properties.
      Moreover microbial shelf-life was reduced to 4 d compared to the 7 obtained for
      control and dipped samples.

PMID- 27706814
TI  - Consumer Acceptance of a Polyphenolic Coffee Beverage.
AB  - The objective of this study was to determine if Chardonnay grape seed pomace
      (GSP), a waste stream of wine production, could be used as a functional
      ingredient in brewed coffee. Two consumer panels were conducted to assess the
      acceptance of coffee at coffee replacement (w/w) values of 0% (control), 6.25%,
      12.50%, 18.75%, or 25% GSP. The 1st consumer panel (n = 80) assessed the coffee
      samples served "black." The 2nd panel (n = 67) assessed the coffee samples with
      adjustment (that is, sweeteners, milk, and cream) options available. Consumer
      sensory evaluation involved evaluating the 5 treatments individually for
      acceptance of appearance, aroma, taste/flavor, and overall acceptance using a 9
      point hedonic scale. A check-all-that-apply questionnaire surveyed the sensory
      attributes describing aroma, appearance, and taste/flavor of the samples. Oxygen
      radical absorbance capacity was used to measure the effects of antioxidant levels
      in GSP coffee samples. Results showed that GSP could be added at 6.25%
      replacement without significantly affecting the overall consumer acceptance of
      coffee compared to the control (0% GSP). Above 6.25% GSP supplementation, the
      coffee beverage was described as more tan, milky, watery/dilute, and mild, and
      was generally less accepted by the consumers. GSP also increased the antioxidant
      capacity of the coffee compared to the control (0% GSP), with no significant
      differences among replacement values. Therefore, 6.25% GSP replacement is
      recommended for creating coffee beverages acceptable to consumers. Further in
      vivo investigation may substantiate the free-radical scavenging capacity of GSP
      coffee and its potential health benefits.

PMID- 27706815
TI  - Influence of the Isolation Method on the Technofunctional Properties of Protein
      Isolates from Lupinus angustifolius L.
AB  - The technofunctional properties of 2 protein isolates from Lupinus angustifolius
      L. Vitabor isolated by different procedures were investigated. The lupin protein
      isolate prepared by aqueous alkaline extraction with subsequent isoelectric
      precipitation (ILP) showed a significantly higher degree of protein denaturation
      and lower denaturation temperatures than the one obtained by aqueous salt-induced
      extraction followed by dilutive precipitation (MLP) as determined by differential
      scanning calorimetry. Rheological investigations revealed higher firmness and a
      viscoelastic solid-like behavior of ILP, in contrast to MLP that showed
      viscoelastic, liquid-like properties. Protein solubility of MLP was higher
      compared to ILP and solubility minima were slightly different for both lupin
      protein isolates. The protein isolates exhibited different technofunctional
      properties with ILP showing higher water binding capacity, lower oil binding
      capacity and lower emulsifying capacity than MLP. This reflects the different
      putative application of both lupin protein isolates as food ingredients, for
      example for ILP as a moisture enhancer and for MLP as a "natural" emulsifier in
      mixed food systems.

PMID- 27706816
TI  - Prediagnosis body mass index and waist-hip circumference ratio in association
      with colorectal cancer survival.
AB  - The association of obesity on survival among patients with colorectal cancer
      (CRC) has not been well characterized. We investigated the association of
      prediagnostic body mass index (BMI)/waist-hip ratio (WHR) and total/cause
      specific mortality in CRC patients. Our study included 1,452 patients who
      participated in two large cohort studies and were diagnosed with CRC during
      follow-up period. Participants were measured for anthropometrics and interviewed
      to collect relevant information at baseline, prior to any cancer diagnosis. Data
      on site-specific cancer incidence and cause-specific mortality were obtained via
      in-person surveys and annual record linkage with cancer and vital statistics
      registries. Cox proportional hazard models were used to evaluate the associations
      of BMI and WHR with survival. A total of 547 participants died during the follow
      up period, including 499 who died of CRC. Relative to normal BMI (18.5 to <25.0
      kg/m2 ), obesity (BMI >= 30 kg/m2 ) was associated with increased mortality
      resulting from all causes [hazard ratio (HR) = 1.5, 95% confidence interval (CI):
      1.1-2.1] and CRC (HR = 1.5, 95% CI: 1.1-2.1). Elevated risk of death was also
      found among underweight patients (BMI < 18.5 kg/m2 ), although not all risk
      estimates were statistically significant. Overweight BMI (25.0 to <30.0 kg/m2 )
      was not associated with risk of death among CRC patients, nor was WHR. In
      conclusion, prediagnostic BMI was associated with survival among CRC patients
      following a U-shape pattern; obesity was associated with high mortality after CRC
      diagnosis. These findings provide support for maintaining healthy weight to
      improve the survival of CRC patients.

PMID- 27706817
TI  - Fluorescence Imaging of Posterior Spiracles from Second and Third Instars of
      Forensically Important Chrysomya rufifacies (Diptera: Calliphoridae).
AB  - Entomological protocols for aging blowfly (Diptera: Calliphoridae) larvae to
      estimate the time of colonization (TOC) are commonly used to assist in death
      investigations. While the methodologies for analyzing fly larvae differ, most
      rely on light microscopy, genetic analysis, or, more rarely, electron microscopy.
      This pilot study sought to improve resolution of larval stage in the forensically
      important blowfly Chrysomya rufifacies using high-content fluorescence microscopy
      and biochemical measures of developmental marker proteins. We established
      fixation and mounting protocols, defined a set of measurable morphometric
      criteria and captured developmental transitions of 2nd instar to 3rd instar using
      both fluorescence microscopy and anti-ecdysone receptor Western blot analysis.
      The data show that these instars can be distinguished on the basis of robust,
      nonbleaching, autofluorescence of larval posterior spiracles. High-content
      imaging techniques using confocal microscopy, combined with morphometric and
      biochemical techniques, may therefore aid forensic entomologists in estimating
      TOC.

PMID- 27706819
TI  - Antibacterial Efficacy of Several Surgical Hand Preparation Products Used by
      Veterinary Students.

PMID- 27706818
TI  - Efficient pole-search algorithm for dynamic polarizability: Toward alternative
      excited-state calculation for large systems.
AB  - This study presents an efficient algorithm to search for the poles of dynamic
      polarizability to obtain excited states of large systems with nonlocal excitation
      nature. The present algorithm adopts a homogeneous search with a constant
      frequency interval and a bisection search to achieve high accuracy. Furthermore,
      the subtraction process of the information about the detected poles from the
      total dynamic polarizability is used to extract the undetected pole
      contributions. Numerical assessments confirmed the accuracy and efficiency of the
      present algorithm in obtaining the excitation energies and oscillator strengths
      of all dipole-allowed excited states. A combination of the present pole-search
      algorithm and divide-and-conquer-based dynamic polarizability calculations was
      found to be promising to treat nonlocal excitations of large systems. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27706820
TI  - The role of primary cilia in obesity and diabetes.
AB  - One in 12 people worldwide suffers from diabetes and more than 90% of affected
      adult individuals are diagnosed with type 2 diabetes mellitus (T2DM). Obesity
      adds to the personal risk to develop T2DM, and both metabolic diseases are
      rampantly increasing worldwide. Over recent years, primary cilia have moved into
      the focus of basic and clinical research, after several human diseases have been
      identified as ciliopathies (i.e., they are linked to ciliary dysfunction). A
      subset of ciliopathies presents with obesity and diabetes, either as core
      symptoms or major complications. Several studies have shown a role for ciliary
      signaling in the satiety signaling centers of the hypothalamus and in other
      metabolically active tissues, such as pancreatic islets. Here, we discuss recent
      advances and perspectives in ciliary metabolic research.

PMID- 27706821
TI  - Higher bioavailability of iron from whole wheat bread compared with iron
      fortified white breads in caco-2 cell model: an experimental study.
AB  - BACKGROUND: Bread, as the staple food of Iranians, with average per capita
      consumption of 300 g d-1 , could potentially be a good vehicle for many
      fortificants, including iron. In this study, iron bioavailability from flat
      breads (three fortified and one whole wheat unfortified) was investigated using
      in vitro simulation of gastrointestinal digestion and absorption in a caco-2 cell
      model. RESULTS: Despite having a lower ferritin/protein ratio in comparison with
      fortified breads, whole wheat bread showed higher iron bioavailability than the
      other three types of bread. Assuming iron bioavailability from the ferrous
      sulfate supplement used as standard was about 10%, the estimated bioavailability
      of iron from the test breads was calculated as 5.0-8.0%. Whole wheat bread (~8%),
      as compared with the fortified breads (~5-6.5%), had higher iron bioavailability.
      CONCLUSION: Iron from unfortified whole wheat bread is more bioavailable than
      from three types of iron-fortified breads. (c) 2016 Society of Chemical Industry.

PMID- 27706822
TI  - Efficiency and apical extrusion of debris: a comparative ex vivo study of four
      retreatment techniques in severely curved root canals.
AB  - AIM: To compare the amount of apically extruded debris and of remaining filling
      material during the removal of root canal filling material using three rotary
      NiTi retreatment instruments or Hedstrom files. METHODOLOGY: Ninety-six severely
      curved human molars of both jaws were selected. The root canals were prepared to
      size X2 (tip size 25, .06 taper) using the ProTaper Next system (Dentsply Sirona,
      Ballaigues, Switzerland), filled with gutta-percha and AH Plus sealer (Dentsply
      De Trey, Konstanz, Germany) and then randomly divided into four experimental
      groups (n = 24 each) with two subgroups of maxillary and mandibular teeth each.
      An experimental model was used as a phantom head to simulate the upper and lower
      jaws. The root filling materials were removed with one of the following files
      using a crown-down preparation technique: I. Hedstrom files (H-files) (VDW,
      Munich, Germany), II. R-Endo (Micro-Mega, Besancon, France), III. Reciproc (VDW)
      and IV. ProTaper Universal Retreatment system (PTU-R) (Dentsply Maillefer).
      Apically extruded material was collected in vials, which were weighed with a
      microbalance (10-5  g) before and after the retreatment. The area of residual
      filling material in the coronal, middle and apical root level was assessed using
      digital analysis. These data were analysed statistically using ANOVA and the
      Kruskal-Wallis test. RESULTS: Reciproc was associated with significantly less
      extruded debris than the H-files (P = 0.009). No significant differences were
      detected amongst the four retreatment techniques concerning residual filling
      material (P = 0.082). The amount of extruded debris and areas of remaining
      filling material were not correlated (P = 0.901). Location of teeth in the
      maxilla or mandible had no impact on the amount of extruded debris within each
      instrument group (P = 0.609). However, when teeth were evaluated in general
      irrespective of the instruments, significantly more debris was extruded in the
      mandibular location (P < 0.001). CONCLUSIONS: All retreatment systems were
      associated with apical extrusion of debris, but H-files extruded significantly
      more material than Reciproc. Remnants of filling material were observed in all
      samples with no significant differences between the four techniques.

PMID- 27706823
TI  - Paper-based 1-MCP treatment suppresses cell wall metabolism and delays softening
      of Huanghua pears during storage.
AB  - BACKGROUND: Huanghua pear will lose its firmness quickly during postharvest
      storage at ambient temperature, and hence has limited storage and marketing
      potential. In this study, Huanghua pears treated with paper containing 0
      (control) or 0.9 MUL L-1 1-methylcyclopropene (1-MCP) for 12 h, and then stored
      at (25 +/- 1)  degrees C for 30 days, were investigated for the effect on fruit
      firmness, cell wall composition and activities of cell wall-degrading enzymes.
      RESULTS: Huanghua pears without 1-MCP treatment softened rapidly during room
      temperature storage and cell wall composition analyses showed an increase in
      water-soluble pectin (WSP) and decreases in cell wall materials (CWM) and cell
      wall components such as Na2 CO3 -soluble pectin (NSP), cellulose and
      hemicellulose. In contrast, the 1-MCP-treated fruits maintained higher firmness
      than the control; also, the treatment prevented the formation of WSP and reduced
      the degradation of CWM and cell wall components including NSP, cellulose and
      hemicellulose. 1-MCP treatment also significantly lowered the activities of cell
      wall-degrading enzymes such as pectinesterase, polygalacturonase, beta
      galactosidase and cellulase during storage. CONCLUSION: 1-MCP treatment can slow
      down the softening of Huanghua pears through reducing cell wall-degrading enzyme
      activities and hence maintain the integrity of the cell wall structure. (c) 2016
      Society of Chemical Industry.

PMID- 27706824
TI  - Variographic analysis of public exposure to electromagnetic radiation due to
      cellular base stations.
AB  - The spatial structure of the vertical component of the electric field emitted by
      base stations in the Brussels region (Belgium) is measured, and studied using the
      variogram. A relationship between the variogram shape and base station antenna
      density in each measurement area is found; the variogram range and sill level are
      shown to depend on cellular base stations' antenna density, following exponential
      laws. Bioelectromagnetics. 37:557-562, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27706825
TI  - Mesenchymal stem cells in tendon repair and regeneration: basic understanding and
      translational challenges.
AB  - Tendon injuries are common and present a clinical challenge because they often
      respond poorly to treatment and require prolonged rehabilitation. Current
      treatments often do not completely repair or regenerate the injured or diseased
      tendon to its native composition, structure, and mechanical properties. Stem cell
      based therapies have brought new hope for tissue repair and regeneration,
      including that for tendon rupture and tendinopathy. Despite tremendous effort and
      progress, the success of stem cell-based studies on tendon repair and
      regeneration has mainly been limited to preclinical studies with few clinical
      applications. In this concise review, we discuss basic understanding and
      translational challenges of using mesenchymal stem cells (MSCs) for tendon repair
      and regeneration, with a focus on (1) tendon stem/progenitor cells (TSPCs) and
      therapeutic approaches using TSPCs and other MSCs, (2) regulation of fate
      determination in MSCs for tendon-lineage differentiation, (3) pretreatment and
      condition of stem/progenitor cells for transplantation, and (4) a treatment
      approach that involves stimulating endogenous stem cells to enhance tendon
      healing. The review concludes with discussion on future directions.

PMID- 27706826
TI  - Long-Term Outcome and Complications Following Prophylactic Laparoscopic-Assisted
      Gastropexy in Dogs.
AB  - OBJECTIVE: To characterize the short- and long-term outcome (>12 months),
      complications, and owner satisfaction following prophylactic laparoscopic
      assisted gastropexy (LAG) in dogs. STUDY DESIGN: Retrospective study. ANIMALS:
      Client-owned dogs (n = 49). METHODS: Dogs that underwent prophylactic LAG at 2
      veterinary academic hospitals were studied. Surgical time, anesthesia time,
      concurrent intra- and extra-abdominal procedures, and intraoperative and
      postoperative complications were recorded following review of medical records.
      Veterinarian and/or owner follow-up was obtained to determine outcome and
      satisfaction with LAG. RESULTS: Five of 49 dogs (10%) experienced complications
      related to abdominal access during LAG. Four percent (2/49) of dogs experienced
      an intraoperative complication. Follow-up information was available for 89% of
      dogs (44/49). Four dogs died of causes unrelated to LAG or gastric dilatation
      volvulus (GDV) in the follow-up period. Two dogs experienced major postoperative
      complications requiring additional veterinary intervention. Thirty percent (13
      dogs) experienced a minor postoperative self-limiting wound-related complication.
      Median follow-up time was 698 days (range, 411-1825). No dogs experienced GDV.
      One hundred percent of dog owners were satisfied with LAG, would repeat the
      procedure in a future pet, and would recommend the procedure to a friend or
      family member. CONCLUSION: LAG was an effective procedure for prevention of GDV
      and was associated with high client satisfaction in this cohort of dogs. A
      moderate rate of postoperative wound complications occurred that were minor and
      self-limiting in nature.

PMID- 27706828
TI  - Pupil old/new effects reflect stimulus encoding and decoding in short-term
      memory.
AB  - We conducted five pupil old/new experiments to examine whether pupil old/new
      effects can be linked to familiarity and/or recollection processes of recognition
      memory. In Experiments 1-3, we elicited robust pupil old/new effects for legal
      words and pseudowords (Experiment 1), positive and negative words (Experiment 2),
      and low-frequency and high-frequency words (Experiment 3). Importantly, unlike
      for old/new effects in ERPs, we failed to find any effects of long-term memory
      representations on pupil old/new effects. In Experiment 4, using the words and
      pseudowords from Experiment 1, participants made lexical decisions instead of
      old/new decisions. Pupil old/new effects were restricted to legal words.
      Additionally requiring participants to make speeded responses (Experiment 5) led
      to a complete absence of old/new effects. Taken together, these data suggest that
      pupil old/new effects do not map onto familiarity and recollection processes of
      recognition memory. They rather seem to reflect strength of memory traces in
      short-term memory, with little influence of long-term memory representations.
      Crucially, weakening the memory trace through manipulations in the experimental
      task significantly reduces pupil/old new effects.

PMID- 27706827
TI  - Early Adolescent Trajectories of Impulsiveness and Sensation Seeking in Children
      of Fathers with Histories of Alcohol and Other Substance Use Disorders.
AB  - BACKGROUND: Problem substance use often begins in adolescence. This vulnerability
      likely stems, at least partially, from relatively rapid increases in sensation
      seeking occurring in early to mid-adolescence and more gradual improvements in
      impulse control occurring through later adolescence. Better understanding how
      these processes develop in high-risk youth may lead to enhanced substance use
      disorder treatment and prevention strategies. METHODS: We characterized
      trajectories of self-reported impulsivity and sensation seeking in 305 FH+ youths
      who at minimum had a father with a history of alcohol or other drug use disorders
      and 81 youths with no family histories of substance use disorders (FH-).
      Assessments started at ages 10 to 12 and continued at 6-month intervals for up to
      42 months. In addition, a subset of 58 FH+ youths who began alcohol or other drug
      use before age 15 (FH+ Users) were compared to 58 FH+ propensity-matched
      adolescents who did not initiate substance use before age 15 (FH+ Non-Users).
      RESULTS: Compared to FH- youths at preadolescence, FH+ youths reported higher
      general impulsivity and higher impulsivity related to poor planning and
      attention. Over time, there were no differential effects of FH status on changes
      in impulsivity or sensation seeking across adolescence. FH+ Users had smaller
      decreases in general impulsivity and impulsivity related to restlessness and
      fidgeting across adolescence than FH+ Non-Users. FH+ Users also had greater
      increases in sensation seeking across adolescence than FH+ Non-Users.
      CONCLUSIONS: Increased impulsivity in FH+ youths may make them less able to
      regulate sensation seeking drives that peak in adolescence, which may contribute
      to their high risk for developing substance use disorders. Additionally, FH+
      adolescents who initiate early use may be at increased risk in part due to
      increased impulsivity coupled with greater increases in sensation seeking.

PMID- 27706829
TI  - Lateral gene transfer, bacterial genome evolution, and the Anthropocene.
AB  - Lateral gene transfer (LGT) has significantly influenced bacterial evolution
      since the origins of life. It helped bacteria generate flexible, mosaic genomes
      and enables individual cells to rapidly acquire adaptive phenotypes. In turn,
      this allowed bacteria to mount strong defenses against human attempts to control
      their growth. The widespread dissemination of genes conferring resistance to
      antimicrobial agents has precipitated a crisis for modern medicine. Our actions
      can promote increased rates of LGT and also provide selective forces to fix such
      events in bacterial populations. For instance, the use of selective agents
      induces the bacterial SOS response, which stimulates LGT. We create hotspots for
      lateral transfer, such as wastewater systems, hospitals, and animal production
      facilities. Conduits of gene transfer between humans and animals ensure rapid
      dissemination of recent transfer events, as does modern transport and
      globalization. As resistance to antibacterial compounds becomes universal, there
      is likely to be increasing selection pressure for phenotypes with adverse
      consequences for human welfare, such as enhanced virulence, pathogenicity, and
      transmission. Improved understanding of the ecology of LGT could help us devise
      strategies to control this fundamental evolutionary process.

PMID- 27706830
TI  - Innovative ways of studying the effect of migration on obesity and diabetes
      beyond the common designs: lessons from the RODAM study.
AB  - Type 2 diabetes and obesity are major global public health problems, with migrant
      populations in high-income countries being particularly affected. Type 2 diabetes
      and obesity are also major threats in low- and middle-income countries, from
      which most migrant populations originate. Transitioning of societies and the
      resulting changes in lifestyles are thought to be major driving forces, but the
      key specific factors within this broad category still need to be determined.
      Migrant studies provide a unique opportunity to understand the potential
      underlying causes of these conditions, but current research is mainly geared
      toward analyzing the differences between migrants and the host populations in the
      countries of settlement. For better understanding, there is a need to extend
      migrant health research across national boundaries. This review discusses
      innovative ways of studying the effect of migration on type 2 diabetes and
      obesity beyond the common designs and the relevance of extending migrant health
      studies across national boundaries in the current era of increasing global
      migration. Specifically, we describe the burden and different methods for
      conducting migrant studies. We use the Research on Obesity and Diabetes among
      African Migrants (RODAM) study as a case study, discussing the methods, some
      results, and lessons learned, including challenges and an essential recipe for
      success that may guide future migrant health research.

PMID- 27706831
TI  - Evaluation of browning ratio in an image analysis of apple slices at different
      stages of instant controlled pressure drop-assisted hot-air drying (AD-DIC).
AB  - BACKGROUND: Computer vision-based image analysis systems are widely used in food
      processing to evaluate quality changes. They are able to objectively measure the
      surface colour of various products since, providing some obvious advantages with
      their objectivity and quantitative capabilities. In this study, a computer vision
      based image analysis system was used to investigate the colour changes of apple
      slices dried by instant controlled pressure drop-assisted hot air drying (AD
      DIC). RESULTS: The CIE L* value and polyphenol oxidase activity in apple slices
      decreased during the entire drying process, whereas other colour indexes,
      including CIE a*, b*, DeltaE and C* values, increased. The browning ratio
      calculated by image analysis increased during the drying process, and a sharp
      increment was observed for the DIC process. The change in 5-hydroxymethylfurfural
      (5-HMF) and fluorescent compounds (FIC) showed the same trend with browning ratio
      due to Maillard reaction. Moreover, the concentrations of 5-HMF and FIC both had
      a good quadratic correlation (R2  > 0.998) with the browning ratio. CONCLUSION:
      Browning ratio was a reliable indicator of 5-HMF and FIC changes in apple slices
      during drying. The image analysis system could be used to monitor colour changes,
      5-HMF and FIC in dehydrated apple slices during the AD-DIC process. (c) 2016
      Society of Chemical Industry.

PMID- 27706832
TI  - Evolutionary potential of upper thermal tolerance: biogeographic patterns and
      expectations under climate change.
AB  - How will organisms respond to climate change? The rapid changes in global climate
      are expected to impose strong directional selection on fitness-related traits. A
      major open question then is the potential for adaptive evolutionary change under
      these shifting climates. At the most basic level, evolutionary change requires
      the presence of heritable variation and natural selection. Because organismal
      tolerances of high temperature place an upper bound on responding to temperature
      change, there has been a surge of research effort on the evolutionary potential
      of upper thermal tolerance traits. Here, I review the available evidence on
      heritable variation in upper thermal tolerance traits, adopting a biogeographic
      perspective to understand how heritability of tolerance varies across space.
      Specifically, I use meta-analytical models to explore the relationship between
      upper thermal tolerance heritability and environmental variability in
      temperature. I also explore how variation in the methods used to obtain these
      thermal tolerance heritabilities influences the estimation of heritable variation
      in tolerance. I conclude by discussing the implications of a positive
      relationship between thermal tolerance heritability and environmental variability
      in temperature and how this might influence responses to future changes in
      climate.

PMID- 27706833
TI  - Pancreatic adenocarcinoma up-regulated factor has oncogenic functions in oral
      squamous cell carcinoma.
AB  - AIMS: Pancreatic adenocarcinoma up-regulated factor (PAUF) is a novel secretory
      protein which promotes tumour progression, metastasis and poor prognosis in
      pancreatic, cervical and colorectal carcinoma. It is also associated with
      gemcitabine resistance in pancreatic cancer cells. However, the expression and
      function of PAUF in oral squamous cell carcinoma (OSCC) remain unknown. METHODS
      AND RESULTS: We performed an immunohistochemical analysis of PAUF in 222
      clinicopathologically characterized cases of OSCC. We also investigated the
      growth, invasion, apoptosis induction and cisplatin resistance of OSCC cells
      under PAUF knockdown treatment. PAUF was localized in normal salivary glands. In
      OSCC, immunostaining for PAUF was found in 52 of 222 patients (23.4%), and
      correlated with nodal metastasis (P < 0.0001) and poor prognosis (P < 0.0001).
      Multivariate analysis using the Cox proportional hazards model identified that
      PAUF expression was an independent predictor of disease-free survival in OSCC (P
      < 0.0001). The down-regulation of PAUF in OSCC cells suppressed cell growth and
      invasion and induced apoptosis and cisplatin sensitivity. CONCLUSIONS: Our
      results suggest that PAUF has tumour-promoting functions in OSCC. It may thus be
      a useful diagnostic and therapeutic marker for OSCC.

PMID- 27706834
TI  - Do contextual factors have a role in periodontal disease?
AB  - AIM: To explore the association between contextual factors and periodontal
      disease. METHODS: We pooled individual-level data from 20,204 35-44-year-olds and
      9,666 65-74-year- olds, who participated in the 3rd National Oral Health Survey
      in China (2005), with province-level data from different sources. The association
      of provincial macroeconomic factors [Gross Domestic Product (GDP) per capita and
      Gini coefficient], health resources (public health expenditure, dentist-to
      population ratio and dental-therapist-to-population ratio), demographic
      composition (proportion of rural population and minority ethnic groups) and
      tobacco industry (tobacco crops, cigarette production and proportion of smokers)
      with the numbers of teeth with periodontal pocket depth (PPD) >= 4 mm and loss of
      attachment (LOA) >= 4 mm were assessed in multilevel models, controlling for
      individual-level demographic, socioeconomic and behavioural factors. RESULTS:
      Only the proportion of smokers at province level was associated with the number
      of teeth with PPD >= 4 mm and only among senior adults. However, public health
      expenditure, dentist-to-population ratio and the proportion of minority ethnic
      groups were associated with the number of teeth with LOA >= 4 mm in both age
      groups. GDP per capita was also associated with the number of teeth with LOA >= 4
      mm only among 35-44-year-olds. CONCLUSION: Contextual factors may contribute to
      periodontal disease and help explain geographical inequalities among Chinese
      adults.

PMID- 27706835
TI  - Using pedagogical approaches to influence evidence-based practice integration -
      processes and recommendations: findings from a grounded theory study.
AB  - AIMS: The study aimed to explore the processes undertaken by nurse academics when
      integrating evidence-based practice (EBP) into their teaching and learning
      practices. This article focuses on pedagogical approaches employed by academics
      to influence evidence-based practice integration into undergraduate programs
      across Australian universities. BACKGROUND: Nursing academics are challenged to
      incorporate a variety of teaching and learning strategies to teach evidence-based
      practice and determine their effectiveness. However, literature suggests that
      there are limited studies available focusing on pedagogical approaches in
      evidence-based practice education. DESIGN: A constructivist grounded theory
      methodology, informed by Charmaz was used for this study. METHODS: Data were
      collected during 2014 from 23 nurse academics across Australian universities
      through semi-structured interviews. Additionally, nine were observed during
      teaching of undergraduate students. Twenty subject outlines were also analysed
      following Charmaz's approach of data analysis. FINDINGS: 'Influencing EBP
      integration' describes the pedagogical approaches employed by academics to
      incorporate EBP knowledge and skills into undergraduate curricula. With the use
      of various teaching and learning strategies, academics attempted to contextualize
      EBP by engaging students with activities aiming to link evidence to practice and
      with the EBP process. Although, some strategies appeared to be engaging, others
      were traditional and seemed to be disengaging for students due to the challenges
      experienced by participants that impeded the use of the most effective teaching
      methods. CONCLUSION: Study findings offer valuable insights into the teaching
      practices and identify some key challenges that require the adoption of
      appropriate strategies to ensure future nurses are well prepared in the paradigm
      of evidence-based practice.

PMID- 27706837
TI  - Propranolol enhances bone healing and implant osseointegration in rats tibiae.
AB  - BACKGROUND: Propranolol, a non-selective beta-blocker widely used to treat
      cardiovascular conditions, favours bone accrual. Accordingly, we hypothesized
      that propranolol could be useful for improving bone healing and osseointegration.
      This in vivo study was designed to investigate the effect of propranolol on bone
      healing and osseointegration in rats' tibiae. METHODS: On 24 Sprague-Dawley rats,
      a unicortical defect was created in the right tibial metaphysis of each rat and a
      custom-made titanium implant was placed in the left tibia. Animals were then
      assigned into two groups (n = 12, each group) and treated daily with either
      propranolol (5 mg/kg: subcutaneous) or saline, for 2 weeks. Then, after killing,
      the volume of the cortical defects (mm3) and the percentages of newly formed bone
      in the defects, were assessed with microcomputed tomography; bone-implant contact
      percentage and peri-implant bone volume/tissue volume were assessed by
      histomorphometry. RESULT: Propranolol-treated rats presented smaller cortical
      defects (1.56 +/- 0.28 mm3 versus 2.04 +/- 0.29 mm3 , p < 0.001) with more bone
      volume/tissue volume (60.6 +/- 7.9% versus 41.1 +/- 10.2%, p < 0.001) compared to
      saline-treated rats. Propranolol also enhanced osseointegration as propranolol
      treated rats presented higher bone-implant-contact (65.0 +/- 13.1% versus 42.5 +/
      8.8%, p < 0.001) and peri-implant bone volume/Tissue volume (73.8 +/- 10.1%
      versus 56.9 +/- 5.7%, p = 0.007) than saline-treated rats. CONCLUSION:
      Propranolol enhanced bone healing and implant osseointegration.

PMID- 27706836
TI  - Identifying nonalcoholic fatty liver disease patients with active fibrosis by
      measuring extracellular matrix remodeling rates in tissue and blood.
AB  - : Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in
      the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed
      to identify patients with more rapidly progressing disease and to demonstrate
      early response to treatment. We describe here a novel method to quantify hepatic
      fibrogenesis flux rates both directly in liver tissue and noninvasively in blood.
      Twenty-one patients with suspected NAFLD ingested heavy water (2 H2 O, 50-mL
      aliquots) two to three times daily for 3-5 weeks prior to a clinically indicated
      liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican
      FSR were measured based on 2 H labeling using tandem mass spectrometry. Patients
      were classified by histology for fibrosis stage (F0-F4) and as having
      nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). Magnetic
      resonance elastography measurements of liver stiffness were also performed.
      Hepatic collagen FSR in NAFLD increased with advancing disease stage (e.g.,
      higher in NASH than nonalcoholic fatty liver, positive correlation with fibrosis
      score and liver stiffness) and correlated with hemoglobin A1C. In addition,
      plasma lumican FSR demonstrated a significant correlation with hepatic collagen
      FSR. CONCLUSION: Using a well-characterized cohort of patients with biopsy-proven
      NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled
      even in advanced fibrosis, a disease that is generally regarded as static and
      slowly progressive. Moreover, hepatic collagen FSR correlates with established
      risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates
      with hepatic collagen FSR, suggesting applications as direct or surrogate
      markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78
      88).

PMID- 27706838
TI  - Alcohol Dependence and Its Relationship With Insomnia and Other Sleep Disorders.
AB  - Sleep-related complaints are widely prevalent in those with alcohol dependence
      (AD). AD is associated not only with insomnia, but also with multiple sleep
      related disorders as a growing body of literature has demonstrated. This article
      will review the various aspects of insomnia associated with AD. In addition, the
      association of AD with other sleep-related disorders will be briefly reviewed.
      The association of AD with insomnia is bidirectional in nature. The
      etiopathogenesis of insomnia has demonstrated multiple associations and is an
      active focus of research. Treatment with cognitive behavioral therapy for
      insomnia is showing promise as an optimal intervention. In addition, AD may be
      associated with circadian abnormalities, short sleep duration, obstructive sleep
      apnea, and sleep-related movement disorder. The burgeoning knowledge on insomnia
      associated with moderate-to-severe alcohol use disorder has expanded our
      understanding of its underlying neurobiology, clinical features, and treatment
      options.

PMID- 27706839
TI  - Influence of type D personality on job stress and job satisfaction in clinical
      nurses: the mediating effects of compassion fatigue, burnout, and compassion
      satisfaction.
AB  - AIMS: To test a hypothetical path model evaluating the influence of type D
      personality on job stress and job satisfaction and to identify the mediating
      effects of compassion fatigue, burnout, and compassion satisfaction among
      clinical nurses in South Korea. BACKGROUND: Personalities susceptible to stress,
      compassion fatigue, and burnout in clinical nurses have negative effects on the
      job stress and job satisfaction. DESIGN: A correlational, cross-sectional design
      was used. METHODS: A convenience sample of 875 clinical nurses was recruited
      between December 2014 - February 2015. The structured questionnaires included the
      Type D personality scale-14, Professional Quality of Life, job stress, job
      satisfaction, and general characteristics. To test the hypothetical path model,
      we performed a path analysis by using the AMOS 18.0 program. FINDINGS: Based on
      the path model, type D personality was significantly associated with compassion
      fatigue, burnout, and compassion satisfaction in our study subjects. Type D
      personality was significantly associated with job stress and job satisfaction via
      the effect of burnout, compassion satisfaction, and job stress. CONCLUSION: Since
      type D personality is associated with job stress and job satisfaction,
      identifying personalities vulnerable to stress would help to address job stress
      and to enhance job satisfaction when nurses have a high level of compassion
      fatigue and burnout and a low level of compassion satisfaction. The development
      of interventions that can reduce negative affect and social inhibition of nurses
      with type D personality and investigation of methods to decrease their compassion
      fatigue and burnout and to increase compassion satisfaction should be encouraged.

PMID- 27706840
TI  - Models of partnership within family-centred care in the acute paediatric setting:
      a discussion paper.
AB  - AIMS: A discussion of partnership in the context of family-centred care in the
      acute paediatric setting, through a critical analysis of partnership models.
      BACKGROUND: Paediatric healthcare practitioners understand the importance of
      family-centred care, but struggle with how to translate the core tenets into
      action and are confused by several rival terms. Partnering relationships are
      included in definitions of family-centred care, yet less is known about
      strategies to fully engage or support parents in these partnerships. A rigorous
      examination of concepts embedded in family-centred care such as partnership may
      provide a better understanding of how to implement the broader concept and
      support exemplary care in today's clinical practice environment. DESIGN:
      Discussion paper. DATA SOURCES: Electronic search (January 2000 - December 2014)
      performed on CINAHL, Medline, EMBASE, Sociological Abstracts and PsychINFO using
      keywords partnership, family-centred care and conceptual framework. Eligible
      references were drawn from the databases, reference lists and expert sources.
      Eight models met inclusion criteria and had currency and relevance to the acute
      paediatric setting. IMPLICATIONS FOR NURSING: Nurses should continue exploring
      partnership in various paediatric contexts given the wide-ranging definitions,
      lack of operational indicators and need for stronger relational statements in
      current models. An examination of key strategies, barriers and facilitators of
      partnership is recommended. CONCLUSION: One partnership model had both high
      overall maturity and best fit with family-centred care principles. All models
      originate from Western and developed countries, indicating that future
      partnership models should be more geographically, culturally and economically
      diverse.

PMID- 27706841
TI  - Periodontal pocketing and gingival bleeding in relation to Nordic diet - results
      from a population-based survey.
AB  - AIM: To examine whether a Nordic diet measured by the Baltic Sea Diet Score
      (BSDS) and the Recommended Finnish Diet Score (RFDS) is associated with
      periodontal condition. MATERIAL AND METHODS: The study population consisted of
      non-smoking, non-diabetic and non-rheumatoid individuals in the Health 2000
      Survey in Finland. Analyses were made in two age groups (30-49 years (n = 1210)
      and 50-79 years (n = 977)) and subsequently in two oral hygiene groups (good oral
      hygiene and poor oral hygiene). The number of sextants with gingival bleeding and
      the number of teeth with deepened periodontal pockets were used as outcome
      variables. Dietary data were collected by a validated food frequency
      questionnaire. RESULTS: Both the BSDS and the RFDS were weakly, although
      statistically significantly associated with less gingival bleeding in the younger
      age group (p = 0.019, p < 0.001). In the older age group, the RFDS or the BSDS
      associated inversely, although inconsistently, with gingival bleeding. RFDS and
      BSDS associated with both gingival bleeding and deepened periodontal pockets
      among those with poor oral hygiene. CONCLUSIONS: The results suggest that the
      Nordic diet in some cases has a favourable effect on periodontal health. These
      findings warrant further studies on the role of diet in periodontal diseases.

PMID- 27706842
TI  - Hierarchical Analysis of Self-Assembled PEGylated Hexaphenylalanine
      Photoluminescent Nanostructures.
AB  - Despite the growing literature about diphenylalanine-based peptide materials, it
      still remains a challenge to delineate the theoretical insight into peptide
      nanostructure formation and the structural features that could permit materials
      with enhanced properties to be engineered. Herein, we report the synthesis of a
      novel peptide building block composed of six phenylalanine residues and eight PEG
      units, PEG8 -F6. This aromatic peptide self-assembles in water in stable and well
      ordered nanostructures with optoelectronic properties. A variety of techniques,
      such as fluorescence, FTIR, CD, DLS, SEM, SAXS, and WAXS allowed us to correlate
      the photoluminescence properties of the self-assembled nanostructures with the
      structural organization of the peptide building block at the micro- and
      nanoscale. Finally, a model of hexaphenylalanine in aqueous solution by molecular
      dynamics simulations is presented to suggest structural and energetic factors
      controlling the formation of nanostructures.

PMID- 27706843
TI  - Organometallic Derivatization of the Nematocidal Drug Monepantel Leads to
      Promising Antiparasitic Drug Candidates.
AB  - The discovery of novel drugs against animal parasites is in high demand due to
      drug-resistance problems encountered around the world. Herein, the synthesis and
      characterization of 27 organic and organometallic derivatives of the recently
      launched nematocidal drug monepantel (Zolvix(r) ) are described. The compounds
      were isolated as racemates and were characterized by 1 H, 13 C, and 19 F NMR
      spectroscopy, mass spectrometry, and IR spectroscopy, and their purity was
      verified by microanalysis. The molecular structures of nine compounds were
      confirmed by X-ray crystallography. The anthelmintic activity of the newly
      designed analogues was evaluated in vitro against the economically important
      parasites Haemonchus contortus and Trichostrongylus colubriformis. Moderate
      nematocidal activity was observed for nine of the 27 compounds. Three compounds
      were confirmed as potentiators of a known monepantel target, the ACR-23 ion
      channel. Production of reactive oxygen species may confer secondary activity to
      the organometallic analogues. Two compounds, namely, an organic precursor (3 a)
      and a cymantrene analogue (9 a), showed activities against microfilariae of
      Dirofilaria immitis in the low microgram per milliliter range.

PMID- 27706844
TI  - Does Topology Dictate the Incidence of the Twist-Bend Phase? Insights Gained from
      Novel Unsymmetrical Bimesogens.
AB  - We prepared a significant number of unsymmetrical liquid-crystalline dimers that
      exhibit the twist-bend nematic phase; a state of matter that exhibits spontaneous
      breaking of mirror symmetry and, for some materials, a microsecond electrooptic
      response. A number of novel unsymmetrical bimesogens were synthesized and in
      comparing their thermal behaviour to previous literature examples, we have
      uncovered an unexpected relationship between the thermal stability of the nematic
      and NTB phases. This relationship demonstrates that molecular shape dictates the
      incidence of this fascinating phase of matter and leads us to speculate as to the
      existence of "twist-bend nematic phases" on length scales beyond those of the
      molecule.

PMID- 27706845
TI  - Versatile Graphene Oxide Putty-Like Material.
AB  - Versatile graphene oxide putty-like material (GOP) with excellent processability
      is developed by mediating a graphene oxide suspension with aniline. Arbitrarily
      predesigned architectures on both microscopic and macroscopic scales can be
      molded easily. GOP cannot only be used as starting material for direct 3D
      printing of particular configurations, but also can be tailored into the
      patterned structures on various substrates for large-scale production of device
      arrays.

PMID- 27706846
TI  - Predictive significance of the European LeukemiaNet classification of genetic
      aberrations in patients with acute myeloid leukaemia undergoing allogeneic stem
      cell transplantation.
AB  - OBJECTIVES: The purpose of this study was to evaluate the predictive capacity of
      the European LeukemiaNet (ELN) classification of genetic risk in patients with
      acute myeloid leukaemia (AML) undergoing allogeneic stem cell transplantation
      (alloSCT). METHODS: We retrospectively analysed 274 patients transplanted at our
      centre between 2004 and 2014. RESULTS: The ELN grouping is comparable to the
      Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG)
      stratification in predicting the outcome after alloSCT [overall P = 0.0064 for
      disease-free survival (DFS), overall P = 0.003 for relapse]. Patients with an
      intermediate-1 profile have a significantly elevated 5-yr relapse incidence as
      compared to favourable risk patients, that is 40% vs. 15%, [hazard ratio (HR)
      2.58, P = 0.048]. An intermediate-1 risk profile is an independent predictor for
      relapse as determined by multivariate Cox regression analysis (HR 3.05, P =
      0.023). In intermediate-1 patients, the presence of an FLT3 internal tandem
      duplication (FLT3-ITD) is associated with a significantly increased relapse
      incidence (P = 0.0323), and a lower DFS (P = 0.0465). FLT3-ITD is an independent
      predictor for overall survival, DFS and relapse incidence in the intermediate-1
      subgroup. CONCLUSIONS: The ELN stratification of genetic risk predicts the
      outcome of patients with AML undergoing alloSCT. Patients with an intermediate-1
      profile have a high risk for treatment failure due to relapse, which prompts the
      development of alternative treatment strategies.

PMID- 27706847
TI  - Structurally diverse dehydroshikimate dehydratase variants participate in
      microbial quinate catabolism.
AB  - Quinate and shikimate can be degraded by a number of microbes. Dehydroshikimate
      dehydratases (DSDs) play a central role in this process, catalyzing the
      conversion of 3-dehydroshikimate to protocatechuate, a common intermediate of
      aromatic degradation pathways. DSDs have applications in metabolic engineering
      for the production of valuable protocatechuate-derived molecules. Although a
      number of Gram-negative bacteria are known to catabolize quinate and shikimate,
      only limited information exists on the quinate/shikimate catabolic enzymes found
      in these organisms. Here, we have functionally and structurally characterized a
      putative DSD designated QuiC1, which is present in some pseudomonads. The QuiC1
      protein is not related by sequence with previously identified DSDs from the Gram
      negative genus, Acinetobacter, but instead shows limited sequence identity in its
      N-terminal half with fungal DSDs. Analysis of a Pseudomonas aeruginosa quiC1 gene
      knock-out demonstrates that it is important for growth on either quinate or
      shikimate. The structure of a QuiC1 enzyme from P. putida reveals that the
      protein is a fusion of two distinct modules: an N-terminal sugar phosphate
      isomerase-like domain associated with DSD activity and a novel C-terminal
      hydroxyphenylpyruvate dioxygenase-like domain. The results of this study
      highlight the considerable diversity of enzymes that participate in
      quinate/shikimate catabolism in different microbes.

PMID- 27706848
TI  - Melatonin attenuates postmyocardial infarction injury via increasing Tom70
      expression.
AB  - Mitochondrial dysfunction leads to reactive oxygen species (ROS) overload,
      exacerbating injury in myocardial infarction (MI). As a receptor for translocases
      in the outer mitochondrial membrane (Tom) complex, Tom70 has an unknown function
      in MI, including melatonin-induced protection against MI injury. We delivered
      specific small interfering RNAs against Tom70 or lentivirus vectors carrying
      Tom70a sequences into the left ventricles of mice or to cultured neonatal murine
      ventricular myocytes (NMVMs). At 48 h post-transfection, the left anterior
      descending coronary arteries of mice were permanently ligated, while the NMVMs
      underwent continuous hypoxia. At 24 h after ischemia/hypoxia, oxidative stress
      was assessed by dihydroethidium and lucigenin-enhanced luminescence,
      mitochondrial damage by transmission electron microscopy and ATP content, and
      cell apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling
      and caspase-3 assay. At 4 weeks after ischemia, cardiac function and fibrosis
      were evaluated in mice by echocardiography and Masson's trichrome staining,
      respectively. Ischemic/hypoxic insult reduced Tom70 expression in cardiomyocytes.
      Tom70 downregulation aggravated post-MI injury, with increased mitochondrial
      fragmentation and ROS overload. In contrast, Tom70 upregulation alleviated post
      MI injury, with improved mitochondrial integrity and decreased ROS production.
      PGC-1alpha/Tom70 expression in ischemic myocardium was increased with melatonin
      alone, but not when combined with luzindole. Melatonin attenuated post-MI injury
      in control but not in Tom70-deficient mice. N-acetylcysteine (NAC) reversed the
      adverse effects of Tom70 deficiency in mitochondria and cardiomyocytes, but at a
      much higher concentration than melatonin. Our findings showed that Tom70 is
      essential for melatonin-induced protection against post-MI injury, by breaking
      the cycle of mitochondrial impairment and ROS generation.

PMID- 27706849
TI  - Assignment of oxime and hydrazone configuration using 1 H-15 N and 13 C-15 N
      coupling measurements at natural abundance.
AB  - Measurement of 1 H-15 N and 13 C-15 N coupling constants at natural abundance is
      demonstrated to be a reliable and generic method to determine the configuration
      of oximes, hydrazines, and related systems. Data on 1 H-15 N and 13 C-15 N
      coupling constants on a variety of systems obtained at natural abundance confirm
      the geometric dependence of the measured 1 H-15 N and 13 C-15 N coupling
      constants. In addition, we summarize a simple "decision-tree" for determining
      configuration based on practical considerations of sample quantity, solubility,
      and complexity. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27706850
TI  - m-Methoxy Substituents in a Tetraphenylethylene-Based Hole-Transport Material for
      Efficient Perovskite Solar Cells.
AB  - Three tetrapheynlethylene derivatives (N,N-di(4-methoxyphenyl)aminophenyl
      substituted tetraphenylethylene; TPE-4DPA) with different methoxy positions (pp-,
      pm-, and po-) have been synthesized and characterized. The methoxy groups can
      control the oxidation potential of the materials, and the electronic properties
      of the derivatives were affected by the position of the methoxy substituents.
      These compounds were synthesized in a facile and cost-effective way, and were
      applied as hole-transport materials in perovskite solar cells. The corresponding
      cell performances were compared with respect to their structure modifications,
      and it was found that the derivative with m-OMe substituents showed the highest
      power conversion efficiency (PCE) of 15.4 %, with a Jsc value of 20.04 mA cm-2 ,
      a Voc value of 1.07 V, and a fill factor (FF) value of 0.72, which is higher than
      the p-OMe and o-OMe substituents. Moreover, the PCE of pm-TPE-4DPA is comparable
      with that of the state-of-the-art 2,2',7,7'-tetrakis(N,N'-di-p
      methoxyphenylamine)-9,9'-spirobifluorene under identical conditions.

PMID- 27706851
TI  - Stable All-Organic Radicals with Ambipolar Charge Transport.
AB  - A series of neutral long-lived purely organic radicals based on the stable [4-(N
      carbazolyl)-2,6-dichlorophenyl]bis(2,4,6-trichlorophenyl)methyl radical adduct
      (Cbz-TTM) is reported herein. All compounds exhibit ambipolar charge-transport
      properties under ambient conditions owing to their radical character. High
      electron and hole mobilities up to 10-2 and 10-3  cm2  V-1  s-1 , respectively,
      were achieved. Xerographic single-layered photoreceptors were fabricated from the
      radicals studied herein, exhibiting good xerographic photosensitivity across the
      visible spectrum.

PMID- 27706852
TI  - Cancer metastasis: Mechanisms of inhibition by melatonin.
AB  - Melatonin is a naturally occurring molecule secreted by the pineal gland and
      known as a gatekeeper of circadian clocks. Mounting evidence indicates that
      melatonin, employing multiple and interrelated mechanisms, exhibits a variety of
      oncostatic properties in a myriad of tumors during different stages of their
      progression. Tumor metastasis, which commonly occurs at the late stage, is
      responsible for the majority of cancer deaths; metastases lead to the development
      of secondary tumors distant from a primary site. In reference to melatonin, the
      vast majority of investigations have focused on tumor development and progression
      at the primary site. Recently, however, interest has shifted toward the role of
      melatonin on tumor metastases. In this review, we highlight current advances in
      understanding the molecular mechanisms by which melatonin counteracts tumor
      metastases, including experimental and clinical observations; emphasis is placed
      on the impact of both cancer and non-neoplastic cells within the tumor
      microenvironment. Due to the broad range of melatonin's actions, the mechanisms
      underlying its ability to interfere with metastases are numerous. These include
      modulation of cell-cell and cell-matrix interaction, extracellular matrix
      remodeling by matrix metalloproteinases, cytoskeleton reorganization, epithelial
      mesenchymal transition, and angiogenesis. The evidence discussed herein will
      serve as a solid foundation for urging basic and clinical studies on the use of
      melatonin to understand and control metastatic diseases.

PMID- 27706853
TI  - Cross-sectional study showed psychosocial variables, gender and family
      involvement played an important role in an adolescent weight management
      programme.
AB  - AIM: This study aimed to investigate the psychosocial gains perceived by
      overweight adolescents attending a 12-week weight management programme and to
      analyse gender-specific differences. METHODS: A quantitative cross-sectional
      study was conducted with a sample of 70 overweight adolescents aged between 12
      and 18 (52.9% girls), evaluated at baseline and at week 12 using anthropometric
      measurements and self-reported questionnaires. We analysed gender-specific
      differences related to body self-esteem, social life, relationships with their
      family, physical comfort, health responsibility, perceived benefits of the
      intervention, self-efficacy and adherence. We further investigated whether the
      variables at week 12 would predict changes in their body mass index. RESULTS:
      While weight had a greater impact on the body self-esteem of girls, both at
      baseline and week 12, boys reported higher self-efficacy and adherence as well as
      a greater perception of the benefits of the intervention at week 12. The body
      mass index change was positively associated with body self-esteem, relationships
      within the family and self-efficacy and adherence. CONCLUSION: Gender specifics
      and the role of psychosocial variables must be taken into account during weight
      management programmes for adolescents, and it is important to include the family
      throughout the entire process.

PMID- 27706854
TI  - Two different mechanosensitive calcium responses in Muller glial cells of the
      guinea pig retina: Differential dependence on purinergic receptor signaling.
AB  - Tractional forces or mechanical stimulation are known to induce calcium responses
      in retinal glial cells. The aim of the study was to determine the characteristics
      of calcium responses in Muller glial cells of the avascular guinea pig retina
      induced by focal mechanical stimulation. Freshly isolated retinal wholemounts
      were loaded with Mitotracker Deep Red (to fill Muller cells) and the calcium
      sensitive dye Fluo-4/AM. The inner retinal surface was mechanically stimulated
      with a micropipette tip for 10 ms. Stimulation induced two different cytosolic
      calcium responses in Muller cells with different kinetics in dependence on the
      distance from the stimulation site. Muller cells near the stimulation site
      displayed an immediate and long-lasting calcium response with high amplitude.
      This response was mediated by calcium influx from the extracellular space likely
      triggered by activation of ATP-insensitive P2 receptors. More distant Muller
      cells displayed, with a delay of 2.4 s, transient calcium responses which
      propagated laterally in a wave-like fashion. Propagating calcium waves were
      induced by a calcium-independent release of ATP from Muller cells near the
      stimulation site, and were mediated by a release of calcium from internal stores
      triggered by ATP, acting in part at P2Y1 receptors. The data suggest that
      mechanically stimulated Muller cells of the guinea pig retina release ATP which
      induces a propagating calcium wave in surrounding Muller cells. Propagating
      calcium waves may be implicated in the spatial regulation of the neuronal
      activity and homeostatic glial functions, and may transmit gliosis-inducing
      signals across the retina. Mechanical stimulation of guinea pig Muller cells
      induces two calcium responses: an immediate response around the stimulation site
      and propagating calcium waves. Both responses are differentially mediated by
      activation of purinergic receptors. GLIA 2016 GLIA 2017;65:62-74.

PMID- 27706855
TI  - Placebo and nocebo effects as major components of the treatment of itch.

PMID- 27706856
TI  - Performance of third-trimester combined screening model for prediction of adverse
      perinatal outcome.
AB  - OBJECTIVE: To explore the potential value of third-trimester combined screening
      for the prediction of adverse perinatal outcome (APO) in the general population
      and among small-for-gestational-age (SGA) fetuses. METHODS: This was a nested
      case-control study within a prospective cohort of 1590 singleton gestations
      undergoing third-trimester evaluation (32 + 0 to 36 + 6 weeks' gestation).
      Maternal baseline characteristics, mean arterial blood pressure, fetoplacental
      ultrasound and circulating biochemical markers (placental growth factor (PlGF),
      lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who
      subsequently had an APO (n = 148) and in a control group without perinatal
      complications (n = 902). APO was defined as the occurrence of stillbirth,
      umbilical artery cord blood pH < 7.15, 5-min Apgar score < 7 or emergency
      operative delivery for fetal distress. Logistic regression models were developed
      for the prediction of APO in the general population and among SGA cases (defined
      as customized birth weight < 10th centile). RESULTS: The prevalence of APO was
      9.3% in the general population and 27.4% among SGA cases. In the general
      population, a combined screening model including a-priori risk (maternal
      characteristics), estimated fetal weight (EFW) centile, umbilical artery
      pulsatility index (UA-PI), estriol and PlGF achieved a detection rate for APO of
      26% (area under receiver-operating characteristics curve (AUC), 0.59 (95% CI,
      0.54-0.65)), at a 10% false-positive rate (FPR). Among SGA cases, a model
      including a-priori risk, EFW centile, UA-PI, cerebroplacental ratio, estriol and
      PlGF predicted 62% of APO (AUC, 0.86 (95% CI, 0.80-0.92)) at a FPR of 10%.
      CONCLUSIONS: The use of fetal ultrasound and maternal biochemical markers at 32
      36 weeks provides a poor prediction of APO in the general population. Although it
      remains limited, the performance of the screening model is improved when applied
      to fetuses with suboptimal fetal growth. Copyright (c) 2016 ISUOG. Published by
      John Wiley & Sons Ltd.

PMID- 27706857
TI  - Blood cells serve as a source of factor-inducing rapid ischemic tolerance in
      brain.
AB  - Ischemic tolerance (IT) has gained attention as an attractive strategy for
      improving stroke outcome. Recently, it was shown that signal responsible for
      rapid IT induction (tolerance induction factor - TIF) is transmitted via
      circulating blood. In this study, we have hypothesized about the role of the
      blood cell compartment in TIF production. We used hind-limb ischemia to generate
      TIF as a rapid preconditioning against transient middle cerebral artery occlusion
      (MCAO). The essential properties of protein synthesis inhibitors actinomycin D
      and cycloheximide were utilized to obtain the following results: (i) TIF is
      proteinaceous. Hind-limb ischemia mediates gene expression followed by
      translation, resulting in the production of TIF. Blocking of each of these two
      steps in protein synthesis resulted in rapid infarct evolution (281.5 +/- 23.37
      and 330.4 +/- 71.8 mm3 , respectively). (ii) Tourniquet-treated muscle is not a
      source of TIF. Actinomicine D injected into rat prior to tolerance induction
      significantly suppressed RNA synthesis in blood cells and muscle tissue. Cross
      circulation of those rats (donors) with control animals (recipients) did not
      mediate significant infarct reduction (272.9 +/- 12.45 mm3 ), even when hind-limb
      ischemia was performed before MCAO in the recipient (223.2 +/- 37.51 mm3 ). (iii)
      Blood cells serve as a source of TIF. Preischemic transfusion of plasma-free,
      protein-synthesis-inactive blood cells, which were obtained from tolerant animals
      did not reduce infarct volume in recipients (131 +/- 16.1 mm3 ) in a range
      comparable with their protein-synthesis-active counterparts (17.2 +/- 12 mm3 ).
      We can conclude that blood cells are associated with the induction of rapid IT
      via production of a bioactive proteinaceous substance.

PMID- 27706858
TI  - Complications of intrauterine intravascular blood transfusion: lessons learned
      after 1678 procedures.
AB  - OBJECTIVE: Maternal alloimmunization to fetal red-blood-cell antigens is a major
      cause of fetal anemia, which can lead to hydrops and perinatal death if
      untreated. The cornerstone of management during pregnancy is intrauterine
      intravascular blood transfusion (IUT). Although this procedure is considered
      relatively safe, complications continue to occur. The aim of this study was to
      evaluate rates of procedure-related complications and perinatal loss following
      IUT, and their change over time, in order to identify factors leading to improved
      outcome. METHODS: This was a retrospective analysis of all IUTs for red-cell
      alloimmunization performed at the national referral center for fetal therapy in
      The Netherlands, from 1988 to 2015. Differences in complication rates and their
      associations with alterations in transfusion technique after 2001 were assessed.
      RESULTS: Between 1988 and 2015, 1678 IUTs were performed in 589 fetuses. For IUTs
      performed in 2001 and onwards, there was significant improvement in survival
      (88.6% vs 97.0%, P < 0.001) and a decline in procedure-related complications per
      fetus (9.8% vs 3.3%, P = 0.001) and per procedure (3.4% vs 1.2%, P = 0.003)
      compared with those performed before 2001. Procedure-related perinatal loss
      declined from 4.7% to 1.8% per fetus (P = 0.053). Beneficial changes in
      transfusion technique were routine use of fetal paralysis, increased use of
      intrahepatic transfusion and avoidance of arterial puncture. CONCLUSIONS: IUT has
      become an increasingly safe procedure in recent years when performed by
      experienced hands. The chosen technique should be fine-tuned according to the
      patient's individual situation. The declining complication rates are most likely
      related to center volume: this rare procedure is best performed in experienced
      fetal therapy centers. (c) 2016 Authors. Ultrasound in Obstetrics & Gynecology
      published by John Wiley & Sons Ltd on behalf of International Society of
      Ultrasound in Obstetrics and Gynecology.

PMID- 27706859
TI  - Diffusion-weighted magnetic resonance imaging of the fetal brain in intrauterine
      growth restriction.
AB  - OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DWI) is a sensitive
      method for assessing brain maturation and detecting brain lesions, providing
      apparent diffusion coefficient (ADC) values as a measure of water diffusion.
      Abnormal ADC values are seen in ischemic brain lesions, such as those associated
      with acute or chronic hypoxia. The aim of this study was to assess whether ADC
      values in the fetal brain were different in fetuses with severe intrauterine
      growth restriction (IUGR) compared with normal controls. METHODS: Brain magnetic
      resonance imaging (MRI) with single-shot axial DWI (b = 0 and b = 700 s/mm2 ) was
      performed in 30 fetuses with severe IUGR (estimated fetal weight < 3rd centile
      with absent or reversed umbilical artery Doppler flow) and in 24 normal controls
      of similar gestational age. Brain morphology and biometry were analyzed. ADC
      values were measured in frontal and occipital white matter, centrum semiovale,
      thalami, cerebellar hemisphere and pons. Frontal-occipital and frontal-cerebellar
      ADC ratios were calculated, and values were compared between IUGR fetuses and
      controls. RESULTS: There was no difference in gestational age at MRI between IUGR
      and control fetuses (IUGR, 30.2 +/- 1.6 weeks vs controls, 30.7 +/- 1.4 weeks).
      Fetal brain morphology and signals were normal in all fetuses. Brain dimensions
      (supratentorial +/- infratentorial) were decreased (Z-score, < -2) in 20 (66.7%)
      IUGR fetuses. Compared with controls, IUGR fetuses had significantly lower ADC
      values in frontal white matter (1.97 +/- 0.23 vs 2.17 +/- 0.22 * 10-3 mm2 /s; P <
      0.0001), thalami (1.04 +/- 0.15 vs 1.13 +/- 0.10 *10-3 mm2 /s; P = 0.0002),
      centrum semiovale (1.86 +/- 0.22 vs 1.97 +/- 0.23 *10-3 mm2 /s; P = 0.01) and
      pons (0.85 +/- 0.19 vs 0.94 +/- 0.12 *10-3 mm2 /s; P = 0.043). IUGR fetuses had a
      lower frontal-occipital ADC ratio than did normal fetuses (1.00 +/- 0.11 vs 1.08
      +/- 0.05; P = 0.003). CONCLUSIONS: ADC values in IUGR fetuses were significantly
      lower than in normal controls in the frontal white matter, thalami, centrum
      semiovale and pons, suggesting abnormal maturation in these regions. However, the
      prognostic value of these ADC changes is still unknown. Copyright (c) 2016 ISUOG.
      Published by John Wiley & Sons Ltd.

PMID- 27706860
TI  - Visuomotor signals for reaching movements in the rostro-dorsal sector of the
      monkey thalamic reticular nucleus.
AB  - The thalamic reticular nucleus (TRN) collects inputs from the cerebral cortex and
      thalamus and, in turn, sends inhibitory outputs to the thalamic relay nuclei.
      This unique connectivity suggests that the TRN plays a pivotal role in regulating
      information flow through the thalamus. Here, we analyzed the roles of TRN neurons
      in visually guided reaching movements. We first used retrograde transneuronal
      labeling with rabies virus, and showed that the rostro-dorsal sector of the TRN
      (TRNrd) projected disynaptically to the ventral premotor cortex (PMv). In other
      experiments, we recorded neurons from the TRNrd or PMv while monkeys performed a
      visuomotor task. We found that neurons in the TRNrd and PMv showed visual-, set-,
      and movement-related activity modulation. These results indicate that the TRNrd,
      as well as the PMv, is involved in the reception of visual signals and in the
      preparation and execution of reaching movements. The fraction of neurons that
      were non-selective for the location of visual signals or the direction of
      reaching movements was greater in the TRNrd than in the PMv. Furthermore, the
      fraction of neurons whose activity increased from the baseline was greater in the
      TRNrd than in the PMv. The timing of activity modulation of visual-related and
      movement-related neurons was similar in TRNrd and PMv neurons. Overall, our data
      suggest that TRNrd neurons provide motor thalamic nuclei with inhibitory inputs
      that are predominantly devoid of spatial selectivity, and that these signals
      modulate how these nuclei engage in both sensory processing and motor output
      during visually guided reaching behavior.

PMID- 27706861
TI  - Doubly N-Fused [24]Pentaphyrin Silicon Complex and Its Fluorosilicate: Enhanced
      Mobius Aromaticity in the Fluorosilicate.
AB  - Treatment of nonaromatic N-fused [24]pentaphyrin with trichloromethylsilane in
      the presence of a base afforded doubly N-fused [24]pentaphyrin and its silicon
      complex. Addition of fluoride ion to the silicon complex led to the formation of
      its fluorosilicate as an unprecedented monoanionic six-coordinated SiIV complex
      of porphyrinoid. Treatment of the fluorosilicate with acid led to the recovery of
      the silicon complex. The doubly N-fused pentaphyrin, the silicon complex, and the
      fluorosilicate were all characterized as distinct Mobius aromatic molecules by
      spectroscopic measurements and X-ray crystallographic analyses. Importantly, the
      second N-fusion reaction, Si-incorporation and fluoride addition to the Si-atom
      enhanced the aromaticity of doubly N-fused [24]pentaphyrins in this order. Tamao
      Fleming oxidation of the silicon complex gave beta-keto doubly N-fused
      pentaphyrin and triply fused [24]pentaphyrin, which were nonaromatic and Huckel
      anti-aromatic, respectively.

PMID- 27706862
TI  - Writing a constructive peer review: a young PI perspective.

PMID- 27706863
TI  - Mass spectrometric fragmentation and photocatalytic transformation of nicotine
      and cotinine.
AB  - RATIONALE: Nicotine and cotinine are, respectively, alkaloids produced mainly by
      the Solanaceae plant family, especially tobacco, and its most important human
      metabolite. These compounds are frequently found as contaminants in wastewater or
      landfill samples and they could be used to evaluate pollution by tobacco use. The
      aim of this study is to improve the knowledge about possible transformation
      pathways of nicotine and cotinine. This would help the identification of
      degradants by using HPLC coupled with a high resolving power mass analyzer (LTQ
      Orbitrap). In addition, we evaluated toxicity on bioluminescent photobacteria to
      indicate possible relationships between the formation of transformation products
      and their toxic effects. METHODS: The transformation of nicotine and cotinine and
      the formation of intermediate products were evaluated adopting titanium dioxide
      as photocatalyst. The structural identification of photocatalytic transformation
      products of these two alkaloids was based on LC/multistage MS experiments. High
      resolution MS allowed the elemental composition of these products to be
      hypothesized. The evolution of toxicity as a function of the irradiation time was
      also studied using a bioluminescent photobacterium (Vibrio fischeri) test.
      RESULTS: Several products were formed and characterized using HPLC/HRMSn . The
      main photocatalytic pathways involving nicotine and cotinine appear to be
      hydroxylation, demethylation and oxidation. Nine degradants were formed from
      nicotine, including cotinine. Seven degradants were generated from cotinine.
      There is no transformation product in common between the two studied molecules.
      CONCLUSIONS: The study of photocatalytic degradation allowed us to partially
      simulate human metabolism and the environmental transformation of the bioactive
      alkaloid nicotine. We searched for some of the identified transformation products
      in river water and landfill percolate by solid-phase extraction and HPLC/HRMS and
      eventually their presence was confirmed. These new findings could be of interest
      in further metabolism and environmental pollution studies. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27706864
TI  - Maternal cardiac function at 35-37 weeks' gestation: relationship with birth
      weight.
AB  - OBJECTIVE: To evaluate the relationship between maternal cardiovascular
      parameters and neonatal birth weight and examine the potential value of these
      parameters in improving the prediction of small-for-gestational-age (SGA) and
      large-for-gestational-age (LGA) neonates provided by maternal characteristics and
      medical history. METHODS: In 2835 singleton pregnancies maternal characteristics
      and medical history were recorded and maternal cardiovascular parameters were
      measured. The observed measurements of cardiovascular parameters were expressed
      as multiples of the normal median (MoM) values after adjustment for those
      characteristics found to provide a substantial contribution to their measurement.
      Regression analysis was used to determine the significance of association between
      the normalized values of the cardiovascular parameters with birth-weight Z-score.
      Multivariable logistic regression analysis was then used to determine if the
      maternal factors, fetal biometry and maternal cardiovascular parameters had a
      significant contribution to predicting SGA and LGA neonates. The performance of
      screening was determined by the area under receiver-operating characteristics
      curves (AUC). RESULTS: In the study population there were significant positive
      associations between maternal cardiac output and heart rate with neonatal birth
      weight Z-score, and significant negative associations between total peripheral
      resistance and mean arterial pressure (MAP) with neonatal birth-weight Z-score.
      In pregnancies delivering SGA neonates (n = 249 (8.8%)), cardiac output and heart
      rate were lower and total peripheral resistance and MAP were higher, whereas in
      pregnancies delivering LGA neonates (n = 292 (10.3%)) cardiac output and heart
      rate were higher and total peripheral resistance and MAP were lower. The
      performance of screening for delivery of SGA neonates achieved by maternal
      characteristics and fetal biometry was not improved by the measurement of
      maternal cardiovascular parameters. There was a small but significant improvement
      in the performance of screening for delivery of LGA neonates by maternal factors
      and fetal biometry with the addition of maternal heart rate (comparison of AUC, P
      = 0.0095). CONCLUSIONS: There are significant associations between maternal
      cardiac output, heart rate, total peripheral resistance and MAP and neonatal
      birth-weight Z-score; such findings reflect the close relationship between
      maternal cardiac function and fetal demands. However, assessment of these
      parameters at 35-37 weeks' gestation is unlikely to improve substantially the
      performance of screening for SGA or LGA neonates provided by a combination of
      maternal factors and fetal biometry. Copyright (c) 2016 ISUOG. Published by John
      Wiley & Sons Ltd.

PMID- 27706865
TI  - Occlusal Pressure Redistribution with Single Implant Restorations.
AB  - PURPOSE: To describe the occlusal pressure redistribution in dental arches
      following placement of single posterior implant-supported restorations in
      occlusion with natural dentitions. MATERIALS AND METHODS: Fifteen patients who
      presented for successfully osseointegrated single posterior implant restorations
      participated in the study. Cement-retained, all-ceramic implant crowns were
      fabricated and delivered after adjustment for interproximal contacts, fit, and
      uniform occlusal contacts. Occlusal pressure distribution was recorded with a
      digital sensor that reported contact point forces as a percentage of total
      pressure applied to the sensor. Measurements were taken before and after
      restoration for comparison. The distribution of relative occlusal stress was
      analyzed for statistical significance by location. RESULTS: The results indicated
      that placement of posterior implant-supported restorations increased the bite
      pressure in the sextants containing the restorations by an average of 4.18% (p =
      0.019) of the maximum value registered (maximum bite pressure). The contralateral
      occlusal load was found to decrease by 2.9% (p = 0.047) of the maximum value
      registered; however, there was no significant difference among or between the
      tooth positions. CONCLUSION: Single posterior implant-supported restorations
      significantly increased the percentage (%) of total occlusal pressure in the
      containing sextant and decreased percentage of total occlusal pressure in the
      contralateral sextant. When analyzing restorations by exact position, more
      posterior implant restorations decreased the occlusal pressure applied in
      anterior dentitions.

PMID- 27706866
TI  - Genetic basis for variation in salinity tolerance between stickleback ecotypes.
AB  - Adaptation to different salinities can drive and maintain divergence between
      populations of aquatic organisms. Anadromous and stream ecotypes of threespine
      stickleback (Gasterosteus aculeatus) are an excellent model to explore the
      genetic mechanisms underlying osmoregulation divergence. Using a parapatric pair
      of anadromous and stream stickleback ecotypes, we employed an integrated genomic
      approach to identify candidate genes important for adaptation to different
      salinity environments. Quantitative trait loci (QTL) mapping of plasma sodium
      concentrations under a seawater challenge experiment identified a significant QTL
      on chromosome 16. To identify candidate genes within this QTL, we first conducted
      RNA-seq and microarray analysis on gill tissue to find ecotypic differences in
      gene expression that were associated with plasma Na+ levels. This resulted in the
      identification of ten candidate genes. Quantitative PCR analysis on gill tissue
      of additional Japanese stickleback populations revealed that the majority of the
      candidate genes showed parallel divergence in expression levels. Second, we
      conducted whole-genome sequencing and found five genes that are predicted to have
      functionally important amino acid substitutions. Finally, we conducted genome
      scan analysis and found that eight of these candidate genes were located in
      genomic islands of high differentiation, suggesting that they may be under
      divergent selection. The candidate genes included those involved in ATP synthesis
      and hormonal signalling, whose expression or amino acid changes may underlie the
      variation in salinity tolerance. Further functional molecular analysis of these
      genes will reveal the causative genetic and genomic changes underlying divergent
      adaptation.

PMID- 27706867
TI  - Prevalence and risk factors associated with hardcore smoking among rural daily
      male smokers.
AB  - BACKGROUND AND OBJECTIVES: The existence of smokers who are resistant to smoking
      cessation interventions has attracted considerable interest in recent years.
      Given the paucity of data on that topic in rural China, we aimed to assess the
      prevalence and risk factors of hardcore smoking in rural China. METHODS: A cross
      sectional study was conducted in 14 villages in Shandong, China. A total of 1,287
      male daily smokers were face-to-face interviewed. A multiple logistic regression
      model was used to explore the associations of demographics, environment,
      knowledge and attitudes about smoking, and smoking behavior characteristics with
      hardcore smoking among daily male smokers. A general dominance analysis model was
      used to access the relative contribution of the determinants that were identified
      in the multiple logistic regression. RESULTS: Hardcore smokers constituted 32.9%
      (n = 423) of daily male smokers. Five determinants for hardcore smoking were
      identified in the multiple logistic regression. Dominance analysis showed higher
      level of smoking intensity was the most important determinant of hardcore
      smoking, followed by being a farmer, starting to smoke daily under the age of 20,
      younger age, having fewer smokers around. DISCUSSION AND CONCLUSIONS: This study
      suggests that hardcore smokers account for a substantial proportion of daily male
      smokers and are distinct from other groups of daily smokers. SCIENTIFIC
      SIGNIFICANCE: Specifically tailored tobacco-control efforts should be made to
      address the issues incurred by hardcore smokers. (Am J Addict 2016;25:628-633).

PMID- 27706868
TI  - Synaptic pathology in the cerebellar dentate nucleus in chronic multiple
      sclerosis.
AB  - In multiple sclerosis, cerebellar symptoms are associated with clinical
      impairment and an increased likelihood of progressive course. Cortical atrophy
      and synaptic dysfunction play a prominent role in cerebellar pathology and
      although the dentate nucleus is a predilection site for lesion development,
      structural synaptic changes in this region remain largely unexplored. Moreover,
      the mechanisms leading to synaptic dysfunction have not yet been investigated at
      an ultrastructural level in multiple sclerosis. Here, we report on synaptic
      changes of dentate nuclei in post-mortem cerebella of 16 multiple sclerosis
      patients and eight controls at the histological level as well as an electron
      microscopy evaluation of afferent synapses of the cerebellar dentate and pontine
      nuclei of one multiple sclerosis patient and one control. We found a significant
      reduction of afferent dentate synapses in multiple sclerosis, irrespective of the
      presence of demyelination, and a close relationship between glial processes and
      dentate synapses. Ultrastructurally, we show autophagosomes containing
      degradation products of synaptic vesicles within dendrites, residual bodies
      within intact-appearing axons and free postsynaptic densities opposed to
      astrocytic appendages. Our study demonstrates loss of dentate afferent synapses
      and provides, for the first time, ultrastructural evidence pointing towards
      neuron-autonomous and neuroglia-mediated mechanisms of synaptic degradation in
      chronic multiple sclerosis.

PMID- 27706869
TI  - Myocardial infarction, patient decision delay and help-seeking behaviour: a
      thematic analysis.
AB  - AIMS AND OBJECTIVES: To explore patient decision delay, the symptom experience
      and factors that motivated the patient experiencing myocardial infarction to go
      to the emergency department. BACKGROUND: Reperfusion for myocardial infarction is
      more effective if performed as soon as possible after the onset of symptoms.
      Multiple studies show that prehospital delay is long and can average several
      hours. DESIGN: A qualitative descriptive design using semi-structured interviews.
      METHODS: All consecutive myocardial infarction patients who between July 2013
      January 2014 at a single-centre metropolitan tertiary hospital in Western
      Australia were included. Patient responses to an open-ended question were
      recorded and transcribed verbatim. Data were analysed using Braun & Clarke (Qual
      Res Psychol, 3, 2006, 77-101) thematic analysis method. RESULTS: Of the 367
      eligible, 255 provided consent. Three themes emerged from the qualitative
      analyses: (1) onset and response to symptoms, and this included three subthemes:
      context of the event, diversity of symptom interpretation and response to
      symptoms; (2) help-seeking behaviour, and this included the patient seeking help
      from various lay and professional sources; and (3) help-seeking outcomes, which
      include calling the emergency ambulance, going to emergency department, seeing a
      general practitioner, seeing a general practitioner who advised them to go home.
      CONCLUSION: The context of the event, their symptomatology and the layperson who
      was the first point of contact influenced the decision for the patient to go to
      the emergency department. Many patients used private transport or contacted their
      general practitioner. New knowledge from this study emphasises the importance of
      the layperson understanding the appropriate response is to seek prompt care
      through immediate emergency transport by ambulance to emergency department.
      RELEVANCE TO CLINICAL PRACTICE: This study highlights the need to educate both
      the patient and the wider public, not only to seek prompt care but to also to
      call the emergency ambulance to arrange transport to the emergency department.

PMID- 27706870
TI  - Mass spectrometric monitoring of oxidation of aliphatic C6-C8 hydrocarbons and
      ethanol in low pressure oxygen and air plasmas.
AB  - Experimental and theoretical studies on the oxidation of saturated hydrocarbons
      (n-hexane, cyclohexane, n-heptane, n-octane and isooctane) and ethanol in 28 Torr
      O2 or air plasma generated by a hollow cathode discharge ion source were made.
      Ions corresponding to [M + 15]+ and [M + 13]+ in addition to [M - H]+ and [M -
      3H]+ were detected as major ions where M is the sample molecule. The ions [M +
      15]+ and [M + 13]+ were assigned as oxidation products, [M - H + O]+ and [M - 3H
      + O]+ , respectively. By the tandem mass spectrometry analysis of [M - H + O]+
      and [M - 3H + O]+ , H2 O, olefins (and/or cycloalkanes) and oxygen-containing
      compounds were eliminated from these ions. Ozone as one of the terminal products
      in the O2 plasma was postulated as the oxidizing reagent. As an example, the
      reactions of C6 H14+* with O2 and of C6 H13+ (CH3 CH2 CH+ CH2 CH2 CH3 ) with
      ozone were examined by density functional theory calculations. Nucleophilic
      interaction of ozone with C6 H13+ leads to the formation of protonated ketone,
      CH3 CH2 C(=OH+ )CH2 CH2 CH3 . In air plasma, [M - H + O]+ became predominant over
      carbocations, [M - H]+ and [M - 3H]+ . For ethanol, the protonated acetic acid
      CH3 C(OH)2+ (m/z 61.03) was formed as the oxidation product. The peaks at m/z
      75.04 and 75.08 are assigned as protonated ethyl formate and protonated diethyl
      ether, respectively, and that at m/z 89.06 as protonated ethyl acetate. Copyright
      (c) 2016 John Wiley & Sons, Ltd.

PMID- 27706871
TI  - What Cognitive Psychology Tells Us About Emergency Department Physician Decision
      making and How to Improve It.

PMID- 27706872
TI  - A qualitative study of patient and provider experiences during preoperative care
      transitions.
AB  - AIMS AND OBJECTIVES: To explore the issues and challenges of care transitions in
      the preoperative environment. BACKGROUND: Ineffective transitions play a role in
      a majority of serious medical errors. There is a paucity of research related to
      the preoperative arena and the multiple inherent transitions in care that occur
      there. DESIGN: Qualitative descriptive design was used. METHODS: Semistructured
      interviews were conducted in a 975-bed academic medical centre. RESULTS: A total
      of 30 providers and 10 preoperative patients participated. Themes that arose were
      as follows: (1) need for clarity of purpose of preoperative care, (2) care
      coordination, (3) interprofessional boundaries of care and (4) inadequate time
      and resources. CONCLUSION: Effective transitions in the preoperative environment
      require that providers bridge scope of practice barriers to promote good
      teamwork. Preoperative care that is a product of well-informed providers and
      patients can improve the entire perioperative care process and potentially
      influence postoperative patient outcomes. RELEVANCE TO CLINICAL PRACTICE: Nurses
      are well positioned to bridge the gaps within transitions of care and accordingly
      affect health outcomes.

PMID- 27706873
TI  - Hot Off the Press: The Use of Very Low Concentrations of High-sensitivity
      Troponin T to Rule Out Acute Myocardial Infarction Using a Single Blood Test.

PMID- 27706874
TI  - Confronting one's vulnerability - patients with chest pain participating in a
      high-intensity exercise programme.
AB  - AIMS AND OBJECTIVES: To explain the transitional process that individuals with
      unexplained chest pain undergo while participating in an exercise training
      programme over time. BACKGROUND: Angina-like chest pain in patients with no
      obstructive coronary artery disease is a growing problem. Functional limitations,
      restricted daily activities and reduced quality of life are reported. In
      addition, physical activity is avoided in this population. DESIGN: The study
      follows a qualitative classic grounded theory (Glaser ). METHODS: Three times a
      week for 12 weeks, twelve patients with no obstructive coronary artery disease
      participated in a high-intensity aerobic exercise training programme supervised
      by physiotherapists and nurses. The data collection was based on diaries and
      interviews about the experience and analysed according to the principles of
      classic grounded theory. RESULTS: The core category was identified as
      'confronting one's vulnerability' and included three subcategories: 'balancing
      existential uncertainty', 'transforming bodily perceptions' and 'becoming a more
      capable person'. CONCLUSION: The transition was described as a process of
      becoming more capable. Health professionals should be aware of the significance
      of high-intensity exercise training for people with unexplained chest pain and of
      the underlying dimension of vulnerability. RELEVANCE TO CLINICAL PRACTICE:
      Understanding the transition process that people with unexplained chest pain
      undergo while participating in a high-intensity exercise training programme
      promotes a person-centred approach. Taking this substantive theory into
      consideration will improve the prerequisites for establishing person-centred
      care.

PMID- 27706875
TI  - Patient perspectives on answering questions about sexual orientation and gender
      identity: an integrative review.
AB  - AIMS AND OBJECTIVES: To examine patients' perceptions of being asked about their
      sexual orientation and gender identity in the healthcare setting. BACKGROUND:
      Health disparities exist in the lesbian, gay, bisexual and transgender
      population, but further research is needed to better understand these
      disparities. To address this issue, experts recommend the routine collection of
      sexual orientation and gender identity data in health care. Nurses on the front
      line of patient care play a key role in the collection of these data. However, to
      enable nurses to conduct such assessments it is important to understand the
      perspective of the patients on being asked about their sexual orientation and
      gender identity in a healthcare setting. DESIGN: An integrative review was
      conducted using the methodology proposed by Whittemore and Knafl (Journal of
      Advanced Nursing, 2005, 52, 546). METHODS: Six electronic databases were
      searched, and two reviewers independently reviewed papers for inclusion. Papers
      were included if they were empirical studies, peer-reviewed papers or reports,
      assessing patient perspectives on discussing sexual orientation and gender
      identity in the healthcare setting. RESULTS: Twenty-one relevant studies that met
      the inclusion criteria were identified. A majority of the studies indicated
      patients' willingness to respond to, and a perceived importance of, questions
      about sexual orientation and gender identity. However, fears of homophobia and
      negative consequences hindered willingness to disclose this information.
      CONCLUSIONS: This review indicates that in most cases patients are willing to
      answer routine questions about their sexual orientation in the healthcare setting
      and perceive them as important questions to ask. RELEVANCE TO CLINICAL PRACTICE:
      The findings of this review have implications for nurses looking to incorporate
      questions about sexual orientation into their routine patient assessment. The
      findings indicate that care providers need to be mindful of heteronormative
      assumptions and take steps to ensure they are knowledgeable about lesbian, gay,
      bisexual and transgender health.

PMID- 27706876
TI  - What is the existing evidence supporting the efficacy of compression bandage
      systems containing both elastic and inelastic components (mixed-component
      systems)? A systematic review.
AB  - AIMS AND OBJECTIVES: To analyse current evidence on the efficacy of bandage
      systems containing both elastic and inelastic components (mixed-component
      systems). BACKGROUND: International consensus on the efficacy of types of
      compression systems is difficult to achieve; however, mixed-component systems are
      being promoted as combining the best properties of both elastic and inelastic
      bandage systems and increasingly being used to treat venous leg ulcers in
      practice. DESIGN: A systematic literature review. METHODS: Search terms such as
      venous leg ulcer, varicose ulcer, leg ulcer, compression, bandage, elastic,
      inelastic, short stretch, healing rate, interface pressure, mixed component, two
      layer, four-layer and multi-layer were used in database and hand searches in
      several combinations. Limits were set for years 2005-March 2015 and English
      language publications. RESULTS: A total of 475 studies were identified at initial
      search, and following elimination from abstract and title, this was reduced to 7.
      A further study was identified on Google Scholar, bringing the final number of
      studies fitting inclusion criteria to 8. The following subgroups relating to
      outcomes of efficacy were identified: ulcer healing, maintenance of interface
      pressure, slippage, ease of application and patient quality of life. CONCLUSIONS:
      Mixed-component systems were found to have comparable ulcer healing rates to
      alternative compression systems and be easy to apply; have similar abilities to
      maintain pressure as four-layer bandages and better abilities than short-stretch
      bandages; have less slippage than alternative systems; and to be significantly
      associated with several favourable quality of life outcomes. Clinician skill in
      bandage application was an uncontrolled variable in all eight papers included in
      the review, which may limit reliability of findings. RELEVANCE TO CLINICAL
      PRACTICE: This review synthesises existing evidence on the efficacy of mixed
      component systems and encourages clinicians to regard them as an effective
      alternative to purely elastic or inelastic compression systems. Additionally, it
      highlights the importance of clinician skill in bandage application as a crucial
      determinant of effective compression.

PMID- 27706877
TI  - Mechanism of auditory hypersensitivity in human autism using autism model rats.
AB  - BACKGROUND: Auditory hypersensitivity is one of the major complications in autism
      spectrum disorder. The aim of this study was to investigate whether the auditory
      brain center is affected in autism model rats. METHODS: Autism model rats were
      prepared by prenatal exposure to thalidomide on embryonic day 9 and 10 in
      pregnant rats. The superior olivary complex (SOC), a complex of auditory nuclei,
      was immunostained with anti-calbindin d28k antibody at postnatal day 50. RESULTS:
      In autism model rats, SOC immunoreactivity was markedly decreased. Strength of
      immunostaining of SOC auditory fibers was also weak in autism model rats.
      Surprisingly, the size of the medial nucleus of trapezoid body, a nucleus
      exerting inhibitory function in SOC, was significantly decreased in autism model
      rats. CONCLUSIONS: Auditory hypersensitivity may be, in part, due to impairment
      of inhibitory processing by the auditory brain center.

PMID- 27706878
TI  - Medication communication between nurses and doctors for paediatric acute care: An
      ethnographic study.
AB  - AIMS AND OBJECTIVES: To examine how communication between nurses and doctors
      occurred for managing medications in inpatient paediatric settings. BACKGROUND:
      Communication between health professionals influences medication incidents'
      occurrence and safe care. DESIGN: An ethnographic study was undertaken. METHODS:
      Semi-structured interviews, observations and focus groups were conducted in three
      clinical areas of an Australian tertiary paediatric hospital. Data were
      transcribed verbatim and thematically analysed using the Medication Communication
      Model. RESULTS: The actual communication act revealed health professionals'
      commitment to effective medication management and the influence of professional
      identities on medication communication. Nurses and doctors were dedicated to
      providing safe, effective medication therapy for children, within their scope of
      practice and perceived role responsibilities. Most nurses and junior doctors used
      tentative language in their communication while senior doctors tended to use
      direct language. Irrespective of language style, nurses actively engaged with
      doctors to promote patients' needs. Yet, the medical hierarchical structure,
      staffing and attendant expectations influenced communication for medication
      management, causing frustration among nurses and doctors. Doctors' lack of verbal
      communication of documented changes to medication orders particularly troubled
      nurses. Nurses persisted in their efforts to acquire appropriate orders for safe
      medication administration to paediatric patients. CONCLUSIONS: Collaborative
      practice between nurses and doctors involved complex, symbiotic relationships.
      Their dedication to providing safe medication therapy to paediatric patients
      facilitated effective medication management. At times, shortcomings in
      interdisciplinary communication impacted on potential and actual medication
      incidents. RELEVANCE TO CLINICAL PRACTICE: Understanding of the complexities
      affecting medication communication between nurses and doctors helps to ensure
      interprofessional respect for each other's roles and inherent demands.
      Interdisciplinary education delivered in healthcare organisations would
      facilitate greater clarity in communication related to medications. Encouraging
      the use of concise, clear words in communication would help to promote improved
      understanding between parties, and accuracy and efficacy of medication
      management.

PMID- 27706880
TI  - Genetic-Algorithm-Based Optimization of a Peptidic Scaffold for Sequestration and
      Hydration of CO2.
AB  - Biomimicry is a strategy that makes practical use of evolution to find efficient
      and sustainable ways to produce chemical compounds or engineer products.
      Exploring the natural machinery of enzymes for the production of desired
      compounds is a highly profitable investment, but the design of efficient
      biomimetic systems remains a considerable challenge. An ideal biomimetic system
      self-assembles in solution, binds a desired range of substrates and catalyzes
      reactions with turnover rates similar to the native system. To this end,
      tailoring catalytic functionality in engineered peptides generally requires site
      directed mutagenesis or the insertion of additional amino acids, which entails an
      intensive search across chemical and sequence space. Here we discuss a novel
      strategy for the computational design of biomimetic compounds and processes that
      consists of a) characterization of the wild-type and biomimetic systems; b)
      identification of key descriptors for optimization; c) an efficient search
      through sequence and chemical space to tailor the catalytic capabilities of the
      biomimetic system. Through this proof-of-principle study, we are able to
      decisively understand and identify whether a given scaffold is useful,
      appropriate and tailorable for a given, desired task.

PMID- 27706879
TI  - Acute kidney injury post-major orthopaedic surgery: A single-Centre case-control
      study.
AB  - AIM: To identify risk factors for acute kidney injury following major orthopaedic
      surgery. METHODS: We included all patients undergoing major orthopaedic surgery
      at University Hospital Geelong between 2008 and 2014 in the study. Out of 2188
      surgeries audited, we identified cases of acute kidney injury using the RIFLE
      criteria and matched those to controls 2:1 for age, sex, procedure and chronic
      kidney disease stage. We reviewed their records for risk factors of postoperative
      acute kidney injury, including medications such as gentamicin, diuretics, non
      steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or
      angiotensin receptor blocker use. We reviewed the patients' history of
      cardiovascular disease, chronic liver disease, hypertension and diabetes mellitus
      along with presence of sepsis and obesity. Associations of hypothetical risk
      factors were estimated using conditional logistic regression. RESULTS: We
      identified 164 cases of AKI in an elderly cohort (median age = 73 years).
      Controlling for baseline comorbidities, both diuretic and angiotensin-converting
      enzyme inhibitor or angiotensin receptor blocker use were found to be associated
      with a twofold risk of acute kidney injury (diuretic - OR 2.06 95% CI:1.30-3.26,
      P < 0.005, angiotensin-converting enzyme inhibitor or angiotensin receptor
      blocker use OR 2.09 95% CI:1.31-3.32, P < 0.005). A dose-effect model accounting
      for perioperative nonsteroidal anti-inflammatory drug administration demonstrated
      a linear relationship between the number of times these drugs were given and
      postoperative acute kidney injury risk (OR 1.35 95% CI:1.05-1.73, P = 0.02).
      CONCLUSIONS: We identified perioperative diuretics, non-steroidal anti
      inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin
      receptor blocker to be significantly associated with postoperative AKI. Further
      prospective studies are required to confirm this.

PMID- 27706881
TI  - Efficient and non-toxic gene delivery by anionic lipoplexes based on polyprenyl
      ammonium salts and their effects on cell physiology.
AB  - BACKGROUND: One of the major challenges limiting the development of gene therapy
      is an absence of efficient and safe gene carriers. Among the nonviral gene
      delivery methods, lipofection is considered as one of the most promising. In the
      present study, a set of cationic polyprenyl derivatives
      [trimethylpolyprenylammonium iodides (PTAI)] with different lengths of polyprenyl
      chains (from 7, 8 and 11 to 15 isoprene units) was suggested as a component of
      efficient DNA vehicles. METHODS: Optimization studies were conducted for PTAI in
      combination with co-lipid dioleoylphosphatidylethanolamine on DU145 human
      prostate cancer cells using: size and zeta potential measurements, confocal
      microscopy, the fluorescein diacetate/ethidium bromide test, cell counting, time
      lapse monitoring of cell movement, gap junctional intercellular coupling
      analysis, antimicrobial activity assay and a red blood cell hemolysis test.
      RESULTS: The results obtained show that the lipofecting activity of PTAI allows
      effective transfection of plasmid DNA complexed in negatively-charged lipoplexes
      of 200-500 nm size into cells without significant side effects on cell physiology
      (viability, proliferation, morphology, migration and gap junctional intercellular
      coupling). Moreover, PTAI-based vehicles exhibit a potent bactericidal activity
      against Staphylococcus aureus and Escherichia coli. The developed anionic
      lipoplexes are safe towards human red blood cell membranes, which are not
      disrupted in their presence. CONCLUSIONS: The developed carriers constitute a
      group of promising lipofecting agents of a new type that can be utilized as
      effective lipofecting agents in vitro and they are also an encouraging basis for
      in vivo applications.

PMID- 27706882
TI  - Fecal retention in childhood: Evaluation on ultrasonography.
AB  - BACKGROUND: To assess the usefulness of rectal diameter measurement on
      ultrasonography as a diagnostic tool for fecal retention in children. METHODS:
      One hundred children (median age, 5.0 years), consisting of 80 with functional
      constipation and 20 without constipation, participated in the study. All patients
      underwent physical examination that included digital rectal examination. Forty
      five children underwent ultrasonography in three differential planes: transection
      above the symphysis; under the ischial spine; and at the bladder neck. The
      measurement of the rectal diameter at the transection above the symphysis could
      most easily detect fecal retention and had the closest correlations with
      retention among the three planes. RESULTS: Rectal diameter was wider at all
      measuring points (35.2 vs 20.9 mm above the symphysis, P < 0.0001; 35.7 vs 24.0
      mm under the ischial spine, P < 0.0001; and 19.4 vs 8.7 mm at the bladder neck, P
      < 0.0001) in children with fecal retention than in those with no fecal retention.
      With regard to presence of constipation, children with fecal retention had a
      wider rectal diameter above the symphysis than those with no fecal retention
      (children with functional constipation, 35.3 vs 20.0 mm, P < 0.0001; children
      without constipation: 32.6 vs 14.6 mm, P = 0.0026). The cut-off for the rectal
      diameter measured above the symphysis to identify fecal retention was 27 mm, with
      high sensitivity and specificity (95.5% and 94.1%, respectively). CONCLUSION:
      Ultrasound rectal diameter measurement can be used to detect fecal retention in
      children.

PMID- 27706884
TI  - Optimisation of combi-lipases from Aspergillus niger for the synergistic and
      efficient hydrolysis of soybean oil.
AB  - The enzymatic properties of four lipases (A, B, C and D) from different strains
      of Aspergillus niger, were investigated, and a 3-factor mixture design and
      triangular surface analysis were performed to screen the optimal combi-lipase by
      observing synergistic effects. Lipases B and D differed in optimal pH,
      temperature and substrate specificity. A combi-lipase with 31.2% lipase B and
      68.8% lipase D (w/w, equal to units of 30.36% and 69.64%) exhibited optimal
      hydrolytic activity on soybean oil, which exceeded the sum of the combined
      activities of individual lipases (P < 0.05). Free fatty acid from the hydrolyzed
      soybean oil indicated that the synergistic effect of the combi-lipase resulted
      from the different fatty acid specificities of the two lipases. Overall, combi
      lipase afforded an effective route for the application of lipase enzymes to
      animal feeds.

PMID- 27706883
TI  - Genome-wide sequence data suggest the possibility of pollinator sharing by host
      shift in dioecious figs (Moraceae, Ficus).
AB  - The obligate mutualism of figs and fig-pollinating wasps has been one of the
      classic models used for testing theories of co-evolution and cospeciation due to
      the high species-specificity of these relationships. To investigate the species
      specificity between figs and fig pollinators and to further understand the
      speciation process in obligate mutualisms, we examined the genetic
      differentiation and phylogenetic relationships of four closely related fig
      pollinating wasp species (Blastophaga nipponica, Blastophaga taiwanensis,
      Blastophaga tannoensis and Blastophaga yeni) in Japan and Taiwan using genome
      wide sequence data, including mitochondrial DNA sequences. In addition,
      population structure was analysed for the fig wasps and their host species using
      microsatellite data. The results suggest that the three Taiwanese fig wasp
      species are a single panmictic population that pollinates three dioecious fig
      species, which are sympatrically distributed, have large differences in
      morphology and ecology and are also genetically differentiated. Our results
      illustrate the first case of pollinator sharing by host shift in the subgenus
      Ficus. On the other hand, there are strict genetic codivergences between
      allopatric populations of the two host-pollinator pairs. The possible processes
      that produce these pollinator-sharing events are discussed based on the level and
      pattern of genetic differentiation in these figs and fig wasps.

PMID- 27706885
TI  - Patterns of the co-use of alcohol, marijuana, and emerging tobacco products in a
      national sample of young adults.
AB  - BACKGROUND: Emerging tobacco product use is on the rise in young adults and has
      been linked to alcohol and marijuana use. Little is known about which patterns of
      alcohol, marijuana, and emerging tobacco product co-use are most popular in this
      age group. OBJECTIVES: This study examined the prevalence of a broad spectrum of
      marijuana, alcohol, and tobacco co-use patterns across a variety of tobacco
      products in a national sample of young adults. METHODS: Data were analyzed from a
      sub-set of 18-24 year olds (unweighted n = 3,940) from five waves of the Truth
      Initiative Young Adult Cohort, a national sample of 18-34 year olds. A user
      generated statistical program in R was used to assess all possible patterns of
      past 30-day use of alcohol, marijuana, cigarettes, cigars, e-cigarettes, little
      cigars/cigarillos, hookah, and other tobacco (pipe, chew, dip, snus,
      dissolvables). RESULTS: No past 30-day use of any substance emerged as the most
      popular pattern across all years (42%), followed by exclusive past 30-day alcohol
      use (31%), and past 30-day alcohol use with cigarettes (5%) or marijuana (4%).
      The popularity of exclusive marijuana use increased over time, but only 1%
      reported exclusive marijuana use without the combination of either alcohol or a
      tobacco product. E-cigarette use only emerged in combination with alcohol and was
      the least popular pattern of co-use relative to other patterns. CONCLUSIONS AND
      SCIENTIFIC SIGNIFICANCE: Patterns stress the importance of alcohol among young
      people. Successful substance use prevention should focus on alcohol's co-use with
      a variety of substances of abuse, rather than focus on a single behavior. (Am J
      Addict 2016;25:634-640).

PMID- 27706886
TI  - Study of Predatory Open Access Nursing Journals.
AB  - PURPOSE: The purpose of this study was to identify predatory journals in nursing,
      describe their characteristics and editorial standards, and document experiences
      of authors, peer reviewers, and editors affiliated with these journals. DESIGN:
      Using two sources that list predatory journals, the research team created a list
      of nursing journals. In Phase One, the team collected data on characteristics of
      predatory nursing journals such as types of articles published, article
      processing charge, and peer review process. In Phase Two, the team surveyed a
      sample of authors, reviewers, and editors to learn more about their experiences
      with their affiliated journals. METHODS: Data from the review of predatory
      nursing journals were analyzed using descriptive statistics. Written comments
      were summarized and categorized. FINDINGS: There were 140 predatory nursing
      journals from 75 publishers. Most journals were new, having been inaugurated in
      the past 1 to 2 years. One important finding was that many journals only
      published one or two volumes and then either ceased publishing or published fewer
      issues and articles after the first volume. Journal content varied widely, and
      some journals published content from dentistry and medicine, as well as nursing.
      Qualitative findings from the surveys confirmed previously published anecdotal
      evidence, including authors selecting journals based on spam emails and inability
      to halt publication of a manuscript, despite authors' requests to do so.
      CONCLUSIONS: Predatory journals exist in nursing and bring with them many of the
      "red flags" that have been noted in the literature, including lack of
      transparency about editorial processes and misleading information promoted on
      websites. The number of journals is high enough to warrant concern in the
      discipline about erosion of our scholarly literature. CLINICAL RELEVANCE: Nurses
      rely on the published literature to provide evidence for high-quality, safe care
      that promotes optimal patient outcomes. Research published in journals that do
      not adhere to the highest standards of publishing excellence have the potential
      to compromise nursing scholarship and is an area of concern.

PMID- 27706887
TI  - Increased mitochondrial fusion in a autosomal recessive CMT2A family with
      mitochondrial GTPase mitofusin 2 mutations.
AB  - Charcot-Marie-Tooth type 2A disease (CMT2A) is an inherited peripheral neuropathy
      mainly caused by mutations in the MFN2 gene coding for the mitochondrial fusion
      protein mitofusin 2. Although the disease is mainly inherited in a dominant
      fashion, few cases of early-onset autosomal recessive CMT2A (AR-CMT2A) have been
      reported in recent years. In this study, we characterized the structure of the
      mitochondrial network in cultured primary fibroblasts obtained from AR-CMT2A
      family members. The patient-derived cells showed an increase of the mitochondrial
      fusion with large connected networks and an increase of the mitochondrial volume.
      Interestingly, fibroblasts derived from the two asymptomatic parents showed
      similar changes to a lesser extent. These results support the hypothesis that AR
      CMT2A-related MFN2 mutations acts through a semi-dominant negative mechanism and
      suggest that other biological parameters might show mild alterations in
      asymptomatic heterozygote AR-CMT2A patients. Such alterations could be useful
      biomarkers helping to distinguish MFN2 mutations from variants, a growing
      challenge with the advent of next generation sequencing into routine clinical
      practice.

PMID- 27706889
TI  - Design, Synthesis, and Application of an Optimized Monofluorinated Aliphatic
      Label for Peptide Studies by Solid-State 19 F NMR Spectroscopy.
AB  - A conformationally restricted monofluorinated alpha-amino acid, (3
      fluorobicyclo[1.1.1]pentyl)glycine (F-Bpg), was designed as a label for the
      structural analysis of membrane-bound peptides by solid-state 19 F NMR
      spectroscopy. The compound was synthesized and validated as a 19 F label for
      replacing natural aliphatic alpha-amino acids. Calculations suggested that F-Bpg
      is similar to Leu/Ile in terms of size and lipophilicity. The 19 F NMR label was
      incorporated into the membrane-active antimicrobial peptide PGLa and provided
      information on the structure of the peptide in a lipid bilayer.

PMID- 27706888
TI  - On the interpretation of electron microscopic maps of biological macromolecules.
AB  - The images of flash-frozen biological macromolecules produced by cryo-electron
      microscopy (EM) can be used to generate accurate, three-dimensional, electric
      potential maps for these molecules that resemble X-ray-derived electron density
      maps. However, unlike electron density maps, electric potential maps can include
      negative features that might for example represent the negatively charged,
      backbone phosphate groups of nucleic acids or protein carboxylate side chains,
      which can complicate their interpretation. This study examines the images of
      groups that include charged atoms that appear in recently-published, high
      resolution EM potential maps of the ribosome and beta-galactosidase. Comparisons
      of simulated maps of these same groups with their experimental counterparts
      highlight the impact that charge has on the appearance of electric potential
      maps.

PMID- 27706890
TI  - Global lessons in graft type and pediatric liver allocation: A path toward
      improving outcomes and eliminating wait-list mortality.
AB  - Current literature and policy in pediatric liver allocation and organ procurement
      are reviewed here in narrative fashion, highlighting historical context, ethical
      framework, technical/procurement considerations, and support for a logical way
      forward to an equitable pediatric liver allocation system that will improve
      pediatric wait-list and posttransplant outcomes without adversely affecting
      adults. Where available, varying examples of successful international pediatric
      liver allocation and split-liver policy will be compared to current US policy to
      highlight potential strategies that can be considered globally. Liver
      Transplantation 23:86-95 2017 AASLD.

PMID- 27706891
TI  - Exploring power and influence in nutrition policy in Australia.
AB  - The food industry is often described as having more power and influence in
      nutrition policymaking than nutrition professionals, scientists and other
      practitioners working for the public interest; yet authors often allude to this
      point as an assumed truth, rather than an evidence-based fact. This paper applies
      social network analysis techniques to provide a concise evidence-based
      demonstration of the food industry's capacity to influence nutrition policymaking
      networks in Australia. Network analysis using four rounds of data collection was
      undertaken, and the capacity of individual actors and occupational categories to
      influence policy decision makers were analysed. Network graphs were developed
      using cluster analysis to identify the structure of clusters and the path
      distance of actors from decision makers. The assumed advantage for the 'food
      industry' was present both strategically in overall network position and with
      respect to the number of direct access points to 'decision makers', whereas
      'nutrition professionals' were densely clustered together with limited links to
      key 'decision makers'. The results demonstrate that the food industry holds the
      strategic high ground in advocating their interests to policymakers in the
      contexts studied. Nutrition professionals may be hampered by their reliance on
      strong ties with other nutrition professionals as well as limited direct links to
      'decision makers'.

PMID- 27706892
TI  - Oxygen delivery using neonatal self-inflating bags without reservoirs.
AB  - BACKGROUND: Guidelines recommend avoiding excessive oxygen during neonatal
      resuscitation. Recent studies have suggested that oxygen titration can be
      achieved using a self-inflating bag, but data on the effectiveness of
      resuscitators used in neonatal ventilation are scarce, The aim of this study was
      therefore to determine the amount of oxygen delivered using several brands of
      neonatal self-inflating resuscitation bags without reservoirs under different
      conditions with regard to oxygen flow rate, ventilation rate (VR), peak
      inspiratory pressure (PIP) range, and test lung compliance. METHODS: Oxygen
      concentration was measured under a variety of conditions. Combinations of oxygen
      flow rate (10, 5.0, 3.0 and 1.0 L/min), VR (40, 60 inflations/min), PIP range (20
      25 cmH2 O, 35-40 cmH2 O), and test lung compliance (0.6, 1.0, 3.0, and 5.0
      mL/cmH2 O) were examined using six kinds of self-inflating bag. RESULTS:
      Delivered oxygen concentration varied widely (30.1-96.7%) and had a significant
      positive correlation with gas flow rate in all of the bags. Delivered oxygen
      concentration was also negatively correlated with PIP in all of the bags and with
      VR in some of them. Test lung compliance did not affect delivered oxygen
      concentration. CONCLUSION: The use of neonatal resuscitation self-inflating bags
      without reservoirs resulted in different delivered oxygen concentrations
      depending on gas flow rate, VR, PIP, and manufacturer, but not on lung
      compliance. This suggests that targeted oxygen concentrations could be delivered,
      even in lungs with decreased compliance, during resuscitation.

PMID- 27706893
TI  - How Factor Analysis Results May Change Due to Country Context.
AB  - PURPOSE: To present how factor analysis results of a Practice Environment Scale
      of the Nursing Work Index (PES-NWI) translation changed due to country context.
      DESIGN: Validity and reliability analysis of a cross-culturally adapted, Polish
      translation of the PES-NWI came from a cross-sectional, national survey that
      included 2,605 registered nurses working in surgical (50.4%) and medical (49.6%)
      units of 30 Polish hospitals. METHODS: Exploratory factor analysis (EFA) using
      the principal component analysis (PCA) method with varimax rotation and
      confirmatory factor analysis (CFA) was used to examine factor structure of the
      instrument in the Polish context. Zero-order and partial Pearson correlation
      coefficients were used to establish the range of variance shared by the
      dimensions of the Polish version. The Cronbach's alpha coefficient determined
      internal consistency reliability. The internal consistency of the scale was also
      tested based on Kline's criterion. FINDINGS: The PCA conducted in the sample of
      Polish nurses extracted six factors, explaining together 56% of the total
      variance. The varimax rotation, however, restricted results to five factors,
      explaining 52.7% of the total variance and generating a factor structure closer
      to that based on previous studies. The CFA model, based on a PCA solution with
      five nonorthogonal factors, fitted data better than the theoretically driven
      model. CONCLUSIONS: Dimensions of the PES-NWI nurses' work environments remain
      conceptually consistent in Poland, but load differently. Health system or nursing
      profession factors related to the country context are potential explanations for
      these differences. CLINICAL RELEVANCE: When using a translation of the Practice
      Environment Scale of the Nursing Work Index-Revised to examine the influences of
      work environment quality on nursing and patient outcomes, it is important to
      consider contextual differences when using results to inform policy.

PMID- 27706894
TI  - cGAS-cGAMP-STING: The three musketeers of cytosolic DNA sensing and signaling.
AB  - Innate immunity is the first line of host defense against invading pathogens. The
      detection of aberrant nucleic acids which represent some conserved PAMPs triggers
      robust type I IFN-mediated innate immune responses. Host- or pathogen-derived
      cytosolic DNA binds and activates the DNA sensor cGAS, which synthesizes the
      second messenger 2'3'-cGAMP and triggers STING-dependent downstream signaling.
      Here, we highlight recent progress in cGAS-cGAMP-STING, the Three Musketeers of
      cytosolic DNA sensing and signaling, and their essential roles in infection,
      autoimmune diseases, and cancer. We also focus on the regulation of these
      critical signal components by variant host/pathogen proteins and update our
      understanding of this indispensable pathway to provide new insights for drug
      discovery. (c) 2016 IUBMB Life, 68(11):858-870, 2016.

PMID- 27706895
TI  - Benefits of temporary portocaval shunt during orthotopic liver transplantation
      with vena cava preservation: A propensity score analysis.
AB  - During orthotopic liver transplantation (OLT), clamping of the portal vein
      induces splanchnic venous congestion and accumulation of noxious compounds. These
      adverse effects could increase ischemia/reperfusion injury and subsequently the
      risk of graft dysfunction, especially for grafts harvested from extended criteria
      donors (ECDs). Temporary portocaval shunt (TPCS) could prevent these
      complications. Between 2002 and 2013, all OLTs performed in our center were
      retrospectively analyzed and a propensity score matching analysis was used to
      compare the effect of TPCS in 686 patients (343 in each group). Patients in the
      TPCS group required fewer intraoperative transfusions (median number of packed
      red blood cells-5 versus 6; P = 0.02; median number of fresh frozen plasma-5
      versus 6; P = 0.02); had improvement of postoperative biological parameters
      (prothrombin time, Factor V, international normalized ratio, alkaline
      phosphatase, and gamma-glutamyltransferase levels); and showed significant
      reduction of biliary complications (4.7% versus 10.2%; P = 0.006). Survival
      analysis revealed that TPCS improved 3-month graft survival (94.2% versus 88.6%;
      P = 0.01) as well as longterm survival of elderly (ie, age > 70 years) donor
      grafts (P = 0.02). In conclusion, the use of TPCS should be recommended
      especially when considering an ECD graft. Liver Transplantation 23 174-183 2017
      AASLD.

PMID- 27706897
TI  - Reply.

PMID- 27706896
TI  - The soluble mannose receptor is released from the liver in cirrhotic patients,
      but is not associated with bacterial translocation.
AB  - BACKGROUND & AIMS: Intestinal bacterial translocation is involved in activation
      of liver macrophages in cirrhotic patients. Macrophages play a key role in liver
      inflammation and are involved in the pathogenesis of cirrhosis and complications.
      Bacterial translocation may be determined by presence of bacterial DNA and
      macrophage activation, by the soluble mannose receptor. We hypothesize that the
      soluble mannose receptor is released from hepatic macrophages in cirrhosis and
      associated with bacterial DNA, portal pressure and complications. METHODS: We
      investigated 28 cirrhotic patients set for transjugular intrahepatic
      portosystemic shunt insertion as a result of refractory ascites (n=17), acute
      (n=3), or recurrent variceal bleeding (n=8). We analysed plasma from the portal
      and hepatic veins for bacterial DNA and soluble mannose receptor with qPCR and
      ELISA. RESULTS: The median soluble mannose receptor level was elevated in the
      hepatic vein compared with the portal vein (0.57(interquartile range 0.31) vs
      0.55(0.40) mg/L, P=.005). The soluble mannose receptor levels were similar in
      bacterial DNA-positive and -negative patients. The soluble mannose receptor level
      in the portal and hepatic veins correlated with the portal pressure prior to
      transjugular intrahepatic portosystemic shunt insertion (r=.52, P<.008, both) and
      the levels correlated with Child-Pugh score (r=.63 and r=.56, P<.004, both). We
      observed higher soluble mannose receptor levels in patients with acute variceal
      bleeding compared to other indications (P<.05). CONCLUSION: This study showed
      hepatic soluble mannose receptor excretion with a higher level in the hepatic
      than the portal vein, though with no associations to bacterial DNA. We observed
      associations between soluble mannose receptor levels and portal pressure and
      higher levels in patients with acute variceal bleeding indicating the soluble
      mannose receptor as a marker of complications of cirrhosis, but not bacterial
      translocation.

PMID- 27706898
TI  - Do environmental pollutants increase obesity risk in humans?
AB  - OBJECTIVES: Obesity has become a global epidemic and threat to public health. A
      good understanding of the causes can help attenuate the risk and spread.
      Environmental pollutants may have contributed to the rising global obesity rates.
      Some research reported associations between chemical pollutants and obesity, but
      findings are mixed. This study systematically examined associations between
      chemical pollutants and obesity in human subjects. METHODS: Systematic review of
      relevant studies published between 1 January 1995 and 1 June 2016 by searching
      PubMed and MEDLINE(r). RESULTS: Thirty-five cross-sectional (n = 17) and cohort
      studies (n = 18) were identified that reported on associations between pollutants
      and obesity measures. Of them, 16 studies (45.71%) reported a positive
      association; none reported a sole inverse association; three (8.57%) reported a
      null association only; six (17.14%) reported both a positive and null
      association; seven (20.00%) reported a positive and inverse association; and
      three studies (8.57%) reported all associations (positive, inverse and null).
      Most studies examined the association between multiple different pollutants,
      different levels of concentration and in subsamples, which results in mixed
      results. Thirty-three studies reported at least one positive association between
      obesity and chemicals, such as polychlorinated biphenyls, biphenyl A,
      dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene and more.
      Certain chemicals, such as biphenyl A, were more likely to have high ORs ranging
      from 1.0 to 3.0, whereas highly chlorinated polychlorinated biphenyls were more
      likely to have negative ORs. Effects of chemicals on the endocrine system and
      obesity might vary by substance, exposure level, measure of adiposity and subject
      characteristics (e.g. sex and age). CONCLUSIONS: Accumulated evidences show
      positive associations between pollutants and obesity in humans. Future large,
      long-term, follow-up studies are needed to assess impact of chemical pollutants
      on obesity risk and related mechanisms.

PMID- 27706899
TI  - Folate-decorated arginine-based poly(ester urea urethane) nanoparticles as
      carriers for gambogic acid and effect on cancer cells.
AB  - Gambogic acid (GA) exhibits a broad spectrum of anticancer activity and low
      chemotoxicity to normal tissues. However, poor aqueous solubility and sensitivity
      to hydrolysis make its pharmaceutical applications a challenge. Linear and
      branched Arg-based poly(ester urea urethane)s (Arg-PEUUs), folate (FA)-conjugated
      Arg PEUUs (FA-Arg-PEUUs), and their self-assembled nanoparticles (NPs) were
      designed, synthesized, and studied as the potential GA carriers for cancer
      treatment. The average diameters of linear or branched Arg-PEUU/FA-Arg-PEUU NPs
      were 98-267 nm. FA-Arg-PEUU NPs adhered onto and were internalized into HeLa and
      A549 cells, and showed no cytotoxicity. The GA loading efficiency in the NP
      carriers ranged from 40 to 98%, depending on the feed weight ratio of GA to Arg
      PEUU and the Arg-PEUU polymer structure (i.e., linear vs. branched). The GA at 2
      ug/mL concentration delivered by the FA-Arg-PEUU NP carriers had higher
      cytotoxicity and induced a higher apoptosis percentage against folate receptor
      (FR)-overexpressed HeLa or HCT116 than Arg-PEUU NPs. When compared to the free GA
      treatment, the GA loaded in the FA-Arg-PEUU NP carriers also led to significant
      loss of the mitochondrial membrane potential in a higher percentage of the cancer
      cell population and more DNA fragmentation. The GA loaded in FA-Arg-PEUU NP
      carriers at as low as 0.6 ug/mL GA concentration led to lower MMP-2 and MMP-9
      activity of cancer cells compared to free GA, suggesting that GA-loaded Arg-PEUU
      NPs may have greater potential to reduce cancer cell invasion and metastasis than
      free GA. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 475
      490, 2017.

PMID- 27706900
TI  - OMIP-037: 16-color panel to measure inhibitory receptor signatures from multiple
      human immune cell subsets.

PMID- 27706901
TI  - Targeting a Targeted Drug: An Approach Toward Hypoxia-Activatable Tyrosine Kinase
      Inhibitor Prodrugs.
AB  - Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over
      the past 15 years, are limited in their clinical application due to serious side
      effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into
      2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very
      different stabilities over 24 h; however, fast reductive activation via E. coli
      nitroreductase could be confirmed for both panels. The anticancer activity and
      signaling inhibition of the compounds against various human cancer cell lines
      were evaluated in cell culture. These data, together with molecular docking
      simulations, revealed distinct differences in the impact of structural
      modifications on drug binding to the enzymes: whereas the catalytic pocket of the
      epidermal growth factor receptor (EGFR) accepted all new erlotinib derivatives,
      the vascular endothelial growth factor receptor (VEGFR)-inhibitory potential in
      the case of the sunitinib prodrugs was dramatically diminished by derivatization.
      In line, hypoxia dependency of ERK signaling inhibition was observed with the
      sunitinib prodrugs, while oxygen levels had no impact on the activity of the
      erlotinib derivatives. Overall, proof of principle could be shown for this
      concept, and the results obtained are an important basis for the future
      development of tyrosine kinase inhibitor prodrugs.

PMID- 27706902
TI  - Artificial Spores: Cytocompatible Coating of Living Cells with Plant-Derived
      Pyrogallol.
AB  - Cell nanoencapsulation, generating cell-in-shell structures ("artificial
      spores"), provides a chemical toolbox for controlling the cellular behaviors and
      functional characteristics of individual cells. Among the shell materials studied
      so far, naturally occurring polyphenolic compounds, including polydopamine and
      tannic acid, have intensively been employed in cell-surface engineering, because
      their material-independent coating property eliminates an extra priming step for
      inducing subsequent shell formation. Albeit successful in generating cell-in
      shell structures, the coating of polyphenolic compounds generally requires
      alkaline conditions and/or high salt conditions, which are not compatible with
      certain cell types. In this work, we demonstrate that the nanocoating of
      individual cells with a plant-derived phenolic compound, pyrogallol (1,2,3
      trihydroxybenzene), occurs at mildly alkaline pH of 7.8 in an isotonic buffer.
      Three different cell types (anucleate, microbial, and mammalian cells) are coated
      with pyrogallol without noticeable decrease in cell viability. The protocol
      developed in this work could be applied to other polyphenolic compounds, and,
      considering the many polyphenols identified as a coating material, provides an
      advanced chemical tool in cell-surface engineering.

PMID- 27706904
TI  - Chloroacetate Promotes and Participates in the Oxidative Annulation of
      Pyridines/Isoquinoline by Using Oxygen as the Oxidant.
AB  - The aerobic oxidative annulation of chalcones, pyridines/isoquinoline and ethyl
      chloroacetate to indolizines was achieved by cascade reaction. Various functional
      groups on chalcones were tolerated. And different pyridines derivatives could
      also be suitable substrates. Ethyl chloroacetate is an essential component in
      participating of the oxidative annulation process. Overall, this protocol is very
      practical and efficient by using molecular oxygen as oxidant with high
      selectivity for the annulation product.

PMID- 27706905
TI  - Retracted: Umbelliferone reverses depression-like behavior in chronic
      unpredictable mild stress-induced mice via RIP140/NF-kappaB pathway.
AB  - : The above article from IUBMB Life, published online on October 5th, 2016 in
      Wiley Online Library (http://wileyonlinelibrary.com), has been retracted by
      agreement between the authors, the Journal Editors-in-Chief, Dr. Angelo Azzi and
      Dr. William Whelan, and Wiley Periodicals, Inc. The retraction has been agreed
      because the article was submitted and approved for publication by Chunhua Ma and
      Long Hongyan without consent in any form by the named Corresponding Author, Kong
      Lingdong. REFERENCE: Chunhua, M., Lingdong, K., Hongyan, L. and Zhangqiang, M.
      (2016), Umbelliferone reverses depression-like behavior in chronic unpredictable
      mild stress-induced mice via RIP140/NF-kappaB pathway. IUBMB Life.
      doi:10.1002/iub.1570 (c) 2017 IUBMB Life, 69(9):767-767, 2017.

PMID- 27706903
TI  - Combination of tauroursodeoxycholic acid and N-acetylcysteine exceeds standard
      treatment for acetaminophen intoxication.
AB  - BACKGROUND & AIMS: Acetaminophen overdose in mice is characterized by hepatocyte
      endoplasmic reticulum stress, which activates the unfolded protein response, and
      centrilobular hepatocyte death. We aimed at investigating the therapeutic
      potential of tauroursodeoxycholic acid, a hydrophilic bile acid known to have
      anti-apoptotic and endoplasmic reticulum stress-reducing capacities, in
      experimental acute liver injury induced by acetaminophen overdose. METHODS: Mice
      were injected with 300 mg/kg acetaminophen, 2 hours prior to receiving
      tauroursodeoxycholic acid, N-acetylcysteine or a combination therapy, and were
      euthanized 24 hours later. Liver damage was assessed by serum transaminases,
      liver histology, terminal deoxynucleotidyl transferase dUTP nick end labelling
      staining, expression profiling of inflammatory, oxidative stress, unfolded
      protein response, apoptotic and pyroptotic markers. RESULTS: Acetaminophen
      overdose resulted in a significant increase in serum transaminases, hepatocyte
      cell death, unfolded protein response activation, oxidative stress, NLRP3
      inflammasome activation, caspase 1 and pro-inflammatory cytokine expressions.
      Standard of care, N-acetylcysteine and, to a lesser extent, tauroursodeoxycholic
      treatment were associated with significantly lower transaminase levels,
      hepatocyte death, unfolded protein response activation, oxidative stress markers,
      caspase 1 expression and NLRP3 levels. Importantly, the combination of N
      acetylcysteine and tauroursodeoxycholic acid improved serum transaminase levels,
      reduced histopathological liver damage, UPR-activated CHOP, oxidative stress,
      caspase 1 expression, NLRP3 levels, IL-1beta levels and the expression of pro
      inflammatory cytokines and this to a greater extend than N-acetylcysteine alone.
      CONCLUSIONS: These findings indicate that a combination strategy of N
      acetylcysteine and tauroursodeoxycholic acid surpasses the standard of care in
      acetaminophen-induced liver injury in mice and might represent an attractive
      therapeutic opportunity for acetaminophen-intoxicated patients.

PMID- 27706906
TI  - Valproic acid selectively increases vascular endothelial tissue-type plasminogen
      activator production and reduces thrombus formation in the mouse.
AB  - : Essentials Stimulating endogenous fibrinolysis could be a novel antithrombotic
      strategy. The effect of valproic acid on endothelial tissue plasminogen activator
      in mice was investigated. Valproic acid increased tissue plasminogen activator
      expression in vascular endothelium. Valproic acid reduced fibrin deposition and
      thrombus formation after vascular injury. SUMMARY: Background The endogenous
      fibrinolytic system has rarely been considered as a target to prevent thrombotic
      disease. Tissue-type plasminogen activator (t-PA) production is potently
      increased by histone deacetylase (HDAC) inhibitors in endothelial cells in vitro,
      but whether this translates into increased vascular t-PA production and an
      enhanced fibrinolytic capacity in vivo is unknown. Objectives To determine
      whether the HDAC inhibitor valproic acid (VPA) stimulates production of t-PA in
      the vasculature of mice, and whether VPA pretreatment affects fibrin deposition
      and clot formation after mechanical vessel injury. Methods Mice were injected
      with VPA twice daily for up to 5 days. t-PA mRNA, and antigen expression in the
      mouse aorta and the circulating levels of t-PA were determined. Fibrin and
      thrombus dynamics after mechanical vessel injury were monitored with intravital
      confocal microscopy. Potential effects of VPA on platelets and coagulation were
      investigated. Results and Conclusions We found that VPA treatment increased
      vascular t-PA production in vivo and, importantly, that VPA administration was
      associated with reduced fibrin accumulation and smaller thrombi in response to
      vascular injury, but still was not associated with an increased risk of bleeding.
      Furthermore, we observed that higher concentrations of VPA were required to
      stimulate t-PA production in the brain than in the vasculature. Thus, this study
      shows that VPA can be dosed to selectively manipulate the fibrinolytic system in
      the vascular compartment and reduce thrombus formation in vivo.

PMID- 27706907
TI  - Staphylococcus aureus and Escherichia coli dual-species biofilms on
      nanohydroxyapatite loaded with CHX or ZnO nanoparticles.
AB  - Implant-associated infections are caused by surface-adhering microorganisms
      persisting as biofilms, resistant to host defense and antimicrobial agents. Given
      the limited efficacy of traditional antibiotics, novel strategies may rely on the
      prevention of such infections through the design of new biomaterials. In this
      work, two antimicrobial agents applied to nanohydroxyapatite materials-namely,
      chlorhexidine digluconate (CHX) and zinc oxide (ZnO) nanoparticles-were compared
      concerning their ability to avoid single- or dual-species biofilms of
      Staphylococcus aureus and Escherichia coli. The resulting biofilms were
      quantified by the enumeration of colony-forming units and examined by confocal
      microscopy using both Live/Dead staining and bacterial-specific fluorescent in
      situ hybridization. The sessile population arrangement was also observed by
      scanning electron microscopy. Both biomaterials showed to be effective in
      impairing bacterial adhesion and proliferation for either single- or dual-species
      biofilms. Furthermore, a competitive interaction was observed for dual-species
      biofilms wherein E. coli exhibited higher proliferative capacity than S. aureus,
      an inverse behavior from the one observed in single-species biofilms. Therefore,
      either nanoHA-CHX or nanoHA-ZnO surfaces appear as promising alternatives to
      antibiotics for the prevention of devices-related infections avoiding the
      critical risk of antibiotic-resistant strains emergence. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 105A: 491-497, 2017.

PMID- 27706908
TI  - Graft selection strategy in adult-to-adult living donor liver transplantation:
      When both hemiliver grafts meet volumetric criteria.

PMID- 27706909
TI  - Repair of caudal septal deviation: the fishing line technique.
AB  - BACKGROUND: Repair of caudal septal deviation using currently described methods
      is challenging technically. The aim of this work is to describe a novel and
      simple technique for the treatment of caudal septal deviations that protects the
      nasal tip, by fixating of cartilage to the columella. METHODS: All patients with
      caudal septal deviation operated on between June 2008 to November 2013 in 2 major
      medical centers were operated using the "fishing line technique." Patient
      satisfaction was recorded by a standard questionnaire (16-item Sino-Nasal Outcome
      Test [SNOT-16]), before and after surgery. The fishing line technique was
      performed in 63 patients with a severe caudal septal deviation of which 14 also
      had rhinoplasty. A mucoperichondrial flap was elevated on either side of the
      damaged septal cartilage. The cartilage was excised and remodeled into a straight
      sheet, and then repositioned between the mucoperichondrial flaps, and fixed to
      the septal columella. RESULTS: Mean age of the study group was 36 years. Follow
      up ranged from 24 to 70 months. At the last follow-up, the septum was straight in
      all cases, with no deviation from the nostrils to the choana. Good airway was
      found in 53 patients. Eight patients had partial turbinate hypertrophy with an
      impaired airway, and 2 had severe turbinate hypertrophy. SNOT-16 mean score
      improved from 27 to 10 (p < 0.001). All patients were satisfied with the
      aesthetic outcome. CONCLUSION: The fishing-line technique for severe caudal
      septum deviations is easy to perform and yields satisfactory anatomic and
      aesthetic results.

PMID- 27706911
TI  - Making extra teeth: Lessons from a TRPS1 mutation.
AB  - A Thai mother and her two daughters were affected with tricho-rhino-phalangeal
      syndrome type I. The daughters had 15 and 18 supernumerary teeth, respectively.
      The mother had normal dentition. Mutation analysis of TRPS1 showed a novel
      heterozygous c.3809_3811delACTinsCATGTTGTG mutation in all. This mutation is
      predicted to cause amino acid changes in the Ikaros-like zinc finger domain near
      the C-terminal end of TRPS1, which is important for repressive protein function.
      The results of our study and the comprehensive review of the literature show that
      pathways of forming supernumerary teeth appear to involve APC and RUNX2, the
      genes responsible for familial adenomatous polyposis syndrome and cleidocranial
      dysplasia, respectively. The final pathway resulting in supernumerary teeth seems
      to involve Wnt, a morphogen active during many stages of development. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27706910
TI  - Sweetened ethanol drinking during social isolation: enhanced intake, resistance
      to genetic heterogeneity and the emergence of a distinctive drinking pattern in
      adolescent mice.
AB  - With its ease of availability during adolescence, sweetened ethanol ('alcopops')
      is consumed within many contexts. We asked here whether genetically based
      differences in social motivation are associated with how the adolescent social
      environment impacts voluntary ethanol intake. Mice with previously described
      differences in sociability (BALB/cJ, C57BL/6J, FVB/NJ and MSM/MsJ strains) were
      weaned into isolation or same-sex pairs (postnatal day, PD, 21), and then given
      continuous access to two fluids on PDs 34-45: one containing water and the other
      containing an ascending series of saccharin-sweetened ethanol (3-6-10%). Prior to
      the introduction of ethanol (PDs 30-33), increased water and food intake was
      detected in some of the isolation-reared groups, and controls indicated that
      isolated mice also consumed more 'saccharin-only' solution. Voluntary drinking of
      'ethanol-only' was also higher in a subset of the isolated groups on PDs 46-49.
      However, sweetened ethanol intake was increased in all isolated strain * sex
      combinations irrespective of genotype. Surprisingly, blood ethanol concentration
      (BEC) was not different between these isolate and socially housed groups 4 h into
      the dark phase. Using lickometer-based measures of intake in FVB mice, we
      identified that a predominance of increased drinking during isolation transpired
      outside of the typical circadian consumption peak, occurring ~8.5 h into the dark
      phase, with an associated difference in BEC. These findings collectively indicate
      that isolate housing leads to increased consumption of rewarding substances in
      adolescent mice independent of their genotype, and that for ethanol this may be
      because of when individuals drink during the circadian cycle.

PMID- 27706913
TI  - Longitudinal retention of anatomical knowledge in second-year medical students.
AB  - The Radboud University Medical Center has a problem-based, learner-oriented,
      horizontally, and vertically integrated medical curriculum. Anatomists and
      clinicians have noticed students' decreasing anatomical knowledge and the
      disability to apply knowledge in diagnostic reasoning and problem solving. In a
      longitudinal cohort, the retention of anatomical knowledge gained during the
      first year of medical school among second-year medical students was assessed. In
      May 2011, 346 medical students applied for the second-year gastro-intestinal (GI)
      tract course. The students were asked to participate in a reexamination of a
      selection of anatomical questions of an examination from October 2009. The
      examination consisted of a clinical anatomy case scenario and two computed
      tomography (CT) images of thorax and abdomen in an extended matching format. A
      total of 165 students were included for analysis. In 2011, students scored
      significantly lower for the anatomy examination compared to 2009 with a decline
      in overall examination score of 14.7% (+/-11.7%). Decrease in knowledge was
      higher in the radiological questions, compared to the clinical anatomy cases
      17.5% (+/-13.6%) vs. 7.9% (+/-10.0%), respectively, d = 5.17. In both years, male
      students scored slightly better compared to female students, and decline of
      knowledge seems somewhat lower in male students (13.1% (+/-11.1%) vs. 15.5% (+/
      12.0%), respectively), d = -0.21. Anatomical knowledge in the problem-oriented
      horizontal and vertical integrated medical curriculum, declined by approximately
      15% 1.5 year after the initial anatomy course. The loss of knowledge in the
      present study is relative small compared to previous studies. Anat Sci Educ 10:
      242-248. (c) 2016 American Association of Anatomists.

PMID- 27706912
TI  - A mixed-methods systematic review of the effects of mindfulness on nurses.
AB  - AIM: To review the effects of mindfulness-based interventions on Registered
      Nurses and nursing students. BACKGROUND: Work-related stress among nurses is
      estimated to be the biggest occupational health problem after musculoskeletal
      disorders. DESIGN: A mixed-method systematic review incorporating quantitative
      and qualitative data was conducted. DATA SOURCES: Studies on the effects of
      mindfulness-based interventions for nurses and nursing students published between
      1980 and 2014 were identified through a systematic search in electronic
      databases: Medline, Embase, PsycINFO, Cochrane Library and Cinahl. REVIEW
      METHODS: Data analysis was conducted based on the framework of Thomas and Harden
      (2004). RESULTS: A total of 32 studies, including 17 controlled designs, 11 pre
      post designs and four qualitative designs were reviewed. Meta-analysis suggests
      that mindfulness-based interventions may be effective in significantly reducing
      state anxiety and depression at posttreatment and state anxiety and trait anxiety
      at follow-up. Qualitative studies and uncontrolled studies shed light on benefits
      overlooked in RCTs, including improvements in the well-being of individuals (e.g.
      inner state of calmness, awareness and enthusiasm) and improved performance at
      work (better communication with colleagues and patients, higher sensitivity to
      patients' experiences, clearer analysis of complex situations and emotional
      regulation in stressful contexts). CONCLUSIONS: Mindfulness appeared to improve
      nurses' mental health significantly. It could be used in worksite health
      promotion programmes. Only a few studies have explored the impact of mindfulness
      on nurses' professional behaviours and their relationships with patients and
      colleagues. Future research should further explore the long-term impacts of
      mindfulness on performance and well-being at work using sound methodological
      designs.

PMID- 27706914
TI  - Ferroelectric BiFeO3 as an Oxide Dye in Highly Tunable Mesoporous All-Oxide
      Photovoltaic Heterojunctions.
AB  - As potential photovoltaic materials, transition-metal oxides such as BiFeO3 (BFO)
      are capable of absorbing a substantial portion of solar light and incorporating
      ferroic orders into solar cells with enhanced performance. But the photovoltaic
      application of BFO has been hindered by low energy-conversion efficiency due to
      poor carrier transport and collection. In this work, a new approach of utilizing
      BFO as a light-absorbing sensitizer is developed to interface with charge
      transporting TiO2 nanoparticles. This mesoporous all-oxide architecture, similar
      to that of dye-sensitized solar cells, can effectively facilitate the extraction
      of photocarriers. Under the standard AM1.5 (100 mW cm-2 ) irradiation, the
      optimized cell shows an open-circuit voltage of 0.67 V, which can be enhanced to
      1.0 V by tailoring the bias history. A fill factor of 55% is achieved, which is
      much higher than those in previous reports on BFO-based photovoltaic devices. The
      results provide here a new viable approach toward developing highly tunable and
      stable photovoltaic devices based on ferroelectric transition-metal oxides.

PMID- 27706915
TI  - Genome-wide transcriptome analysis of Aspergillus fumigatus exposed to osmotic
      stress reveals regulators of osmotic and cell wall stresses that are SakAHOG1 and
      MpkC dependent.
AB  - Invasive aspergillosis is predominantly caused by Aspergillus fumigatus, and
      adaptations to stresses experienced within the human host are a prerequisite for
      the survival and virulence strategies of the pathogen. The central signal
      transduction pathway operating during hyperosmotic stress is the high osmolarity
      glycerol mitogen-activated protein kinase cascade. A. fumigatus MpkC and SakA,
      orthologues of the Saccharomyces cerevisiae Hog1p, constitute the primary
      regulator of the hyperosmotic stress response. We compared A. fumigatus wild-type
      transcriptional response to osmotic stress with the DeltampkC, DeltasakA, and
      DeltampkC DeltasakA strains. Our results strongly indicate that MpkC and SakA
      have independent and collaborative functions during the transcriptional response
      to transient osmotic stress. We have identified and characterized null mutants
      for four A. fumigatus basic leucine zipper proteins transcription factors. The
      atfA and atfB have comparable expression levels with the wild-type in DeltampkC
      but are repressed in DeltasakA and DeltampkC DeltasakA post-osmotic stress. The
      atfC and atfD have reduced expression levels in all mutants post-osmotic stress.
      The atfA-D null mutants displayed several phenotypes related to osmotic,
      oxidative, and cell wall stresses. The DeltaatfA and DeltaatfB were shown to be
      avirulent and to have attenuated virulence, respectively, in both Galleria
      mellonella and a neutropenic murine model of invasive pulmonary aspergillosis.

PMID- 27706917
TI  - Enhancing the osteoblastic differentiation through nanoscale surface
      modifications.
AB  - Human mesenchymal stem cells (MSCs) showed larger differentiation into
      osteoblasts on nanoscale amorphous titanium oxide (TiO2 ) coatings in comparison
      to polycrystalline TiO2 coatings or native oxide layers. In this article, we
      showed that the subtle alterations in the surface properties due to a different
      atomic ordering of titanium oxide layers could substantially modify the
      osteoblastic differentiation of MSCs. Amorphous (a) and polycrystalline (c) TiO2
      coatings were deposited on smooth (PT) and microstructured sandblasted/acid
      etched (SLA) Ti substrates using a magnetron sputtering system. The surface
      roughness, water contact angle, structure, and composition were measured using
      confocal microscopy, drop sessile drop, X-ray diffraction, and X-ray
      photoelectron spectroscopy, respectively. The ~70-nm-thick coatings presented a
      well-passivated and uniform TiO2 (Ti4+ ) surface composition, while the
      substrates (native oxide layer) showed the presence of Ti atoms in lower valence
      states. The polycrystalline TiO2 -coated surfaces (cPT and cSLA) showed the same
      cell attachment as the uncoated metallic surfaces (PT and SLA), and in both
      cases, it was lower on the rough than on the smooth surfaces. However, attachment
      and differentiation were significantly increased on the amorphous TiO2 -coated
      surfaces (aPT and aSLA). The amorphous coated Ti surfaces presented the highest
      expression of integrins and production of osteogenic proteins in comparison to
      the uncoated and crystalline-coated Ti surfaces. (c) 2016 Wiley Periodicals, Inc.
      J Biomed Mater Res Part A: 105A: 498-509, 2017.

PMID- 27706916
TI  - Anatomical and functional neuroimaging in awake, behaving marmosets.
AB  - The common marmoset (Callithrix jacchus) is a small New World monkey that has
      gained significant recent interest in neuroscience research, not only because of
      its compatibility with gene editing techniques, but also due to its tremendous
      versatility as an experimental animal model. Neuroimaging modalities, including
      anatomical (MRI) and functional magnetic resonance imaging (fMRI), complemented
      by two-photon laser scanning microscopy and electrophysiology, have been at the
      forefront of unraveling the anatomical and functional organization of the
      marmoset brain. High-resolution anatomical MRI of the marmoset brain can be
      obtained with remarkable cytoarchitectonic detail. Functional MRI of the marmoset
      brain has been used to study various sensory systems, including somatosensory,
      auditory, and visual pathways, while resting-state fMRI studies have unraveled
      functional brain networks that bear great correspondence to those previously
      described in humans. Two-photon laser scanning microscopy of the marmoset brain
      has enabled the simultaneous recording of neuronal activity from thousands of
      neurons with single cell spatial resolution. In this article, we aim to review
      the main results obtained by our group and by our colleagues in applying
      neuroimaging techniques to study the marmoset brain. (c) 2016 Wiley Periodicals,
      Inc. Develop Neurobiol 77: 373-389, 2017.

PMID- 27706919
TI  - The common marmoset: An overview of its natural history, ecology and behavior.
AB  - Callithrix jacchus are small-bodied Neotropical primates popularly known as
      common marmosets. They are endemic to Northeast Brazil and occur in contrasting
      environments such as the humid Atlantic Forest and the dry scrub forest of the
      Caatinga. Common marmosets live in social groups, usually containing only one
      breeding pair. These primates have a parental care system in which individuals
      help by providing assistance to the infants even when they are not related to
      them. Free-ranging groups use relatively small home ranges (0.5-5 hectares) and
      have an omnivorous diet. Because of the shape of their teeth, they actively gouge
      tree bark to extract and consume exudates. When foraging for live prey, they
      adjust their strategy according to the type of prey. The successful use of
      appropriate hunting strategies depends not only on age but also on prey type and
      seems to be mediated by learning and experience. Indeed, common marmosets have
      shown unexpected cognitive abilities, such as true imitation. All these aspects
      seem to have contributed to the ecological success of this species. Callithrix
      jacchus has been widely studied, especially in captivity; even so, a number of
      questions remain to be answered about its biology, ecology, and behavior, both in
      captivity and the wild. A richer understanding of marmosets' natural behavior and
      ecology can have a significant impact on shaping ongoing and future neuroscience
      research. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 244-262, 2017.

PMID- 27706918
TI  - Application of viral vectors to the study of neural connectivities and neural
      circuits in the marmoset brain.
AB  - It is important to study the neural connectivities and functions in primates. For
      this purpose, it is critical to be able to transfer genes to certain neurons in
      the primate brain so that we can image the neuronal signals and analyze the
      function of the transferred gene. Toward this end, our team has been developing
      gene transfer systems using viral vectors. In this review, we summarize our
      current achievements as follows. 1) We compared the features of gene transfer
      using five different AAV serotypes in combination with three different promoters,
      namely, CMV, mouse CaMKII (CaMKII), and human synapsin 1 (hSyn1), in the marmoset
      cortex with those in the mouse and macaque cortices. 2) We used target-specific
      double-infection techniques in combination with TET-ON and TET-OFF using
      lentiviral retrograde vectors for enhanced visualization of neural connections.
      3) We used an AAV-mediated gene transfer method to study the transcriptional
      control for amplifying fluorescent signals using the TET/TRE system in the
      primate neocortex. We also established systems for shRNA mediated gene targeting
      in a neocortical region where a gene is significantly expressed and for
      expressing the gene using the CMV promoter for an unexpressed neocortical area in
      the primate cortex using AAV vectors to understand the regulation of downstream
      genes. Our findings have demonstrated the feasibility of using viral vector
      mediated gene transfer systems for the study of primate cortical circuits using
      the marmoset as an animal model. (c) 2016 Wiley Periodicals, Inc. Develop
      Neurobiol 77: 354-372, 2017.

PMID- 27706920
TI  - Oncostatin m impairs brown adipose tissue thermogenic function and the browning
      of subcutaneous white adipose tissue.
AB  - OBJECTIVE: Since oncostatin m (OSM) is elevated in adipose tissue in conditions
      of obesity and type 2 diabetes in mice and humans, the aim of this study was to
      determine whether this cytokine plays a crucial role in the impairment of brown
      adipose tissue (BAT) activity and browning capacity that has been observed in
      people with obesity. METHODS: C57BL/6J mice rendered obese by high-fat diet,
      their lean controls, and C57BL/6J mice fed a standard diet and implanted
      subcutaneously with a mini pump through a surgical procedure to deliver OSM or
      placebo were used. Preadipocytes or fully differentiated brown adipocytes were
      treated with OSM or vehicle with or without norepinephrine before harvesting. RNA
      was extracted and processed for qPCR analysis. Media from mature adipocytes was
      also collected to measure glycerol levels. RESULTS: Studies demonstrated that OSM
      gene expression was increased in BAT of mice fed a high-fat diet. In addition,
      exogenous OSM impaired BAT activity and the browning capacity of white adipose
      tissue in vitro and in vivo. CONCLUSIONS: Overall, the results reveal a negative
      role for OSM on BAT and on the browning of white adipose tissue. Therefore,
      further studies are necessary to demonstrate whether OSM inhibition is a
      potential treatment for metabolic disorders.

PMID- 27706921
TI  - Mass spectrometric characterisation of darbepoetin alfa biosimilars with C
      terminal arginine residues.
AB  - Human erythropoietin (EPO) and recombinant human EPO (rEPO) are approximately 30
      kDa glycosylated proteins comprising 165 amino acids. Darbepoetin alfa (NESP) is
      a glycosylated protein encompassing five changes in the amino acid sequence of
      human EPO, which contains two extra sugar chains. NESP is under patent protection
      in the USA until May 2024 and in Europe until July 2016, which suggests that the
      number of NESP biosimilars might substantially increase. The detailed
      characterisation of biosimilar products are required to ensure the identity and
      purity of the biosimilar products in terms of safety and efficacy for patients.
      In this study, a mass spectrometric characterisation of NESP biosimilar products
      is demonstrated. The study comprises a time-of-flight mass spectrometry
      characterisation for the asialo-NESPs after sialidase digestion and primary
      structure characterisation using bottom-up analysis after endoproteinase Glu-C
      digestion of the core protein. The study revealed that there was a wide range of
      glycoforms spaced by 365 Da intervals, namely, HexHexNAc units, which indicated
      that NESP biosimilars likely contained more N-acetyllactosamine units in their
      molecules. The bottom-up analysis also showed that the NESP biosimilars, as well
      as a rEPO biosimilar, contain not only the des-arginine product but also the C
      terminal arginine product comprising 166 amino acids, whereas the innovator
      products contain des-arginine EPO comprising only 165 amino acids. The C-terminal
      arginine EPO would be used as a potential marker for doping with EPO bisimilaras.
      These findings also point to a need for the investigation of immunogenicity and
      comparability for the biosimilar products. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 27706922
TI  - Structural and functional analysis of de-N-acetylase PgaB from periodontopathogen
      Aggregatibacter actinomycetemcomitans.
AB  - The oral pathogen Aggregatibacter actinomycetemcomitans uses pga gene locus for
      the production of an exopolysaccharide made up of a linear homopolymer of beta
      1,6-N-acetyl-d-glucosamine (PGA). An enzyme encoded by the pgaB of the pga operon
      in A. actinomycetemcomitans is a de-N-acetylase, which is used to alter the PGA.
      The full length enzyme (AaPgaB) and the N-terminal catalytic domain (residues 25
      290, AaPgaBN) from A. actinomycetemcomitans were cloned, expressed and purified.
      The enzymatic activities of the AaPgaB enzymes were determined using 7
      acetoxycoumarin-3-carboxylic acid as the substrate. The AaPgaB enzymes displayed
      significantly lower de-N-acetylase activity compared with the activity of the
      deacetylase PdaA from Bacillus subtilis, a member of the CE4 family of enzymes.
      To delineate the differences in the activity and the active site architecture,
      the structure of AaPgaBN was determined. The AaPgaBN structure has two metal ions
      in the active site instead of one found in other CE4 enzymes. Based on the
      crystal structure comparisons among the various CE4 enzymes, two residues, Q51
      and R271, were identified in AaPgaB, which could potentially affect the enzyme
      activity. Of the two mutants generated, Q51E and R271K, the variant Q51E showed
      enhanced activity compared with AaPgaB, validating the requirement that an
      activating aspartate residue in the active site is essential for higher activity.
      In summary, our study provides the first structural evidence for a di-nuclear
      metal site at the active site of a member of the CE4 family of enzymes, evidence
      that AaPgaBN is catalytically active and that mutant Q51E exhibits higher de-N
      acetylase activity.

PMID- 27706923
TI  - 2-deoxyglucose inhibits induction of chemokine expression in 3T3-L1 adipocytes
      and adipose tissue explants.
AB  - OBJECTIVE: To determine the influence of glycolytic inhibition on the adipocyte
      inflammatory response. METHODS: To determine the effect of 2-deoxyglucose (2-DOG)
      on the inflammatory response, mature 3T3-L1 adipocytes were co-treated with 2-DOG
      and LPS or TNF. To determine the effect of endoplasmic reticulum stress on TNF
      induced induction of chemokines, adipocytes were pretreated with thapsigargin or
      salubrinal. Chemokine mRNA levels were determined using quantitative real-time
      PCR, and secretion of CCL2 was determined by Western blot. RESULTS: 2-DOG
      treatment reduced the ability of LPS and TNF to induce CCL2 mRNA levels and
      reduced secreted CCL2 protein levels in a dose-dependent manner. A similar
      pattern of mRNA regulation was observed for other chemokines. The attenuation of
      TNF-induced CCL2 mRNA levels occurred regardless of whether glucose or pyruvate
      was present in the media, suggesting that mechanisms other than glycolysis might
      mediate the observed effects. Treatment with the endoplasmic reticulum stressor
      thapsigargin and the endoplasmic reticulum signaling activator salubrinal reduced
      chemokine mRNA levels similarly to 2-DOG. CONCLUSIONS: Collectively, our data
      indicate that 2-DOG suppresses inflammatory chemokine induction in adipocytes.
      The effects of 2-DOG do not seem to be linked to glycolysis but correlate with
      endoplasmic reticulum stress activation.

PMID- 27706924
TI  - The corticospinal tract: Evolution, development, and human disorders.
AB  - The corticospinal tract (CST) plays a major role in cortical control of spinal
      cord activity. In particular, it is the principal motor pathway for voluntary
      movements. Here, we discuss: (i) the anatomic evolution and development of the
      CST across mammalian species, focusing on its role in motor functions; (ii) the
      molecular mechanisms regulating corticospinal tract formation and guidance during
      mouse development; and (iii) human disorders associated with abnormal CST
      development. A comparison of CST anatomy and development across mammalian species
      first highlights important similarities. In particular, most CST axons cross the
      anatomical midline at the junction between the brainstem and spinal cord, forming
      the pyramidal decussation. Reorganization of the pattern of CST projections to
      the spinal cord during evolution led to improved motor skills. Studies of the
      molecular mechanisms involved in CST formation and guidance in mice have
      identified several factors that act synergistically to ensure proper formation of
      the CST at each step of development. Human CST developmental disorders can result
      in a reduction of the CST, or in guidance defects associated with abnormal CST
      anatomy. These latter disorders result in altered midline crossing at the
      pyramidal decussation or in the spinal cord, but spare the rest of the CST.
      Careful appraisal of clinical manifestations associated with CST malformations
      highlights the critical role of the CST in the lateralization of motor control.
      (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 810-829, 2017.

PMID- 27706927
TI  - Different perspectives: Spatial ability influences where individuals look on a
      timed spatial test.
AB  - Learning in anatomy can be both spatially and visually complex. Pedagogical
      investigations have begun exploration as to how spatial ability may mitigate
      learning. Emerging hypotheses suggests individuals with higher spatial reasoning
      may attend to images differently than those who are lacking. To elucidate
      attentional patterns associated with different spatial ability, eye movements
      were measured in individuals completing a timed electronic mental rotation test
      (EMRT). The EMRT was based on the line drawings of Shepherd and Metzler.
      Individuals deduced whether image pairs were rotations (same) or mirror images
      (different). It was hypothesized that individuals with high spatial ability (HSA)
      would demonstrate shorter average fixation durations during problem solving and
      attend to different features of the EMRT than low spatial ability (LSA)
      counterparts. Moreover, question response accuracy would be associated with fewer
      fixations and shorter average response times, regardless of spatial reasoning
      ability. Average fixation duration in the HSA group was shorter than LSA (F(1,8)
      = 7.99; P = 0.022). Importantly, HSA and LSA individuals looked to different
      regions of the EMRT images (Fisher Exact Test: 12.47; P = 0.018); attending to
      the same locations only 34% of the time. Correctly answered questions were
      characterized by fewer fixations per question (F(1, 8) = 18.12; P = 0.003) and
      shorter average response times (F(1, 8) = 23.89; P = 0.001). The results indicate
      that spatial ability may influence visual attention to salient areas of images
      and this may be key to problem solving processes for low spatial individuals.
      Anat Sci Educ 10: 224-234. (c) 2016 American Association of Anatomists.

PMID- 27706926
TI  - Discordant genotyping results using DNA isolated from anti-doping control urine
      samples.
AB  - The UGT2B17 gene deletion polymorphism is known to correlate to urinary
      concentration of testosterone-glucuronide and hence this genotype exerts a large
      impact on the testosterone/epitestosterone (T/E) ratio, a biomarker for
      testosterone doping. The objective of this study was to assess if DNA isolated
      from athletes' urine samples (n = 713) obtained in routine doping controls could
      be targeted for genotyping analysis for future integration in the athlete's
      passport. A control population (n = 21) including both urine and blood DNA was
      used for genotyping concordance test. Another aim was to study a large group (n =
      596) of authentic elite athletes in respect of urinary steroid profile in
      relation to genetic variation. First we found that the genotype results when
      using urine-derived DNA did not correlate sufficiently with the genotype obtained
      from whole blood DNA. Secondly we found males with one or two UGT2B17 alleles had
      higher T/E (mean 1.63 +/- 0.93) than females (mean 1.28 +/- 1.08), p?0.001.
      Unexpectedly, we found that several male del/del athletes in power sports had a
      T/E ?1. If men in power sport exert a different urinary steroid profile needs to
      be further investigated. The other polymorphisms investigated in the CYP17A1,
      UGT2B7 and UGT2B15 genes did not show any associations with testosterone and
      epitestosterone concentrations. Our results show that genotyping using urine
      samples according to our method is not useful in an anti-doping setting. Instead,
      it is of importance for the anti-doping test programs to include baseline values
      in the ABP to minimize any putative impact of genotype. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27706928
TI  - Three-Arm, Biotin-Tagged Carbazole-Dicyanovinyl-Chlorambucil Conjugate:
      Simultaneous Tumor Targeting, Sensing, and Photoresponsive Anticancer Drug
      Delivery.
AB  - The design, synthesis, and in vitro biological studies of a biotin-carbazole
      dicyanovinyl-chlorambucil conjugate (Bio-CBZ-DCV-CBL; 6) are reported. This
      conjugate (6) is a multifunctional single-molecule appliance composed of a thiol
      sensor DCV functionality, a CBZ-derived phototrigger as well as fluorescent
      reporter, and CBL as the anticancer drug, and Bio as the cancer-targeting ligand.
      In conjugate 6, the DCV bond undergoes a thiol-ene click reaction at pH<7 with
      intracellular thiols, thereby shutting down internal charge transfer between the
      donor CBZ and acceptor DCV units, resulting in a change of the fluorescence color
      from green to blue, and thereby, sensing the tumor microenvironment. Subsequent
      photoirradiation results in release of the anticancer drug CBL in a controlled
      manner.

PMID- 27706925
TI  - Minocycline causes widespread cell death and increases microglial labeling in the
      neonatal mouse brain.
AB  - Minocycline, an antibiotic of the tetracycline family, inhibits microglia in many
      paradigms and is among the most commonly used tools for examining the role of
      microglia in physiological processes. Microglia may play an active role in
      triggering developmental neuronal cell death, although findings have been
      contradictory. To determine whether microglia influence developmental cell death,
      we treated perinatal mice with minocycline (45 mg/kg) and quantified effects on
      dying cells and microglial labeling using immunohistochemistry for activated
      caspase-3 (AC3) and ionized calcium-binding adapter molecule 1 (Iba1),
      respectively. Contrary to our expectations, minocycline treatment from embryonic
      day 18 to postnatal day (P)1 caused a > tenfold increase in cell death 8 h after
      the last injection in all brain regions examined, including the primary sensory
      cortex, septum, hippocampus and hypothalamus. Iba1 labeling was also increased in
      most regions. Similar effects, although of smaller magnitude, were seen when
      treatment was delayed to P3-P5. Minocycline treatment from P3 to P5 also
      decreased overall cell number in the septum at weaning, suggesting lasting
      effects of the neonatal exposure. When administered at lower doses (4.5 or 22.5
      mg/kg), or at the same dose 1 week later (P10-P12), minocycline no longer
      increased microglial markers or cell death. Taken together, the most commonly
      used microglial "inhibitor" increases cell death and Iba1 labeling in the
      neonatal mouse brain. Minocycline is used clinically in infant and pediatric
      populations; caution is warrented when using minocycline in developing animals,
      or extrapolating the effects of this drug across ages. (c) 2016 Wiley
      Periodicals, Inc. Develop Neurobiol 77: 753-766, 2017.

PMID- 27706929
TI  - Diagnostic accuracy and cost-effectiveness of different strategies to triage
      women with adnexal masses: a prospective study.
AB  - OBJECTIVE: Transvaginal sonography (TVS) and serum biomarkers are used widely in
      clinical practice to triage women with adnexal masses, but the effectiveness of
      current biomarkers is weak. The aim of this study was to determine the best
      method of diagnosing patients with adnexal masses, in terms of diagnostic
      accuracy and economic costs, among four triage strategies: (1) the International
      Ovarian Tumor Analysis group's simple rules (SR) for interpretation of TVS with
      subjective assessment (SA) by an experienced ultrasound operator when TVS results
      are inconclusive (referred to hereafter as SR +/- SA), (2) SR +/- SA and cancer
      antigen 125 (CA 125), (3) SR +/- SA and human epididymis protein 4 (HE4) and (4)
      SR +/- SA and the risk of malignancy algorithm (ROMA). Our main hypothesis was
      that the addition of the biomarkers to SR +/- SA could improve triaging of these
      patients in terms of diagnostic accuracy (i.e. malignant vs benign). As secondary
      analyses, we estimated the cost effectiveness of the four strategies and the
      diagnostic accuracy of SR +/- SA at the study hospitals. METHODS: Between
      February 2013 and January 2015, 447 consecutive patients who were scheduled for
      surgery for an adnexal mass at the S. Anna and Mauriziano Hospitals in Turin were
      enrolled in this multicenter prospective cohort study. Preoperative TVS was
      performed and preoperative CA 125 and HE4 levels were measured. Pathology reports
      were used to assess the diagnostic accuracy of the four triage strategies and the
      cost of each strategy was calculated. RESULTS: A total of 391 patients were
      included in the analysis: 57% (n = 221) were premenopausal and 43% (n = 170) were
      postmenopausal. The overall prevalence of malignancy was 21%. SR were conclusive
      in 89% of patients and thus did not require SA; the overall performance of SR +/-
      SA showed a sensitivity of 82%, specificity of 92% and positive and negative
      predictive values and positive and negative likelihood ratios of 74%, 95%, 10.5
      and 0.19, respectively. In premenopausal women, mean cost among the four triage
      strategies varied from ?36.41 for SR +/- SA to ?70.12 for SR +/- SA + ROMA. The
      addition of biomarkers to SR +/- SA showed no diagnostic advantage compared with
      SR +/- SA alone and was more costly. Among postmenopausal women, mean cost among
      the four triage strategies varied from ?39.52 for SR +/- SA to ?73.23 for SR +/-
      SA + ROMA. Among these women, SR +/- SA + CA 125 and SR +/- SA + ROMA had a
      higher sensitivity (both 92% (95% CI, 85-99%)) than SR +/- SA (81% (95% CI, 71
      91%)), but SR +/- SA had a higher specificity (84% (95% CI, 77-91%)). SR +/- SA +
      CA 125 and SR +/- SA + ROMA improved diagnostic accuracy, each diagnosing a third
      more malignant adnexal masses. In postmenopausal women, compared with SR +/- SA
      alone, SR +/- SA + CA 125 showed a net reclassification improvement (NRI) of
      28.8% at an extra cost of ?13.00, while the extra cost for SR +/- SA + ROMA was
      ?33.71, with a comparable gain, in terms of NRI, as that of SR +/- SA + CA 125.
      CONCLUSIONS: In our study sample, SR +/- SA seems to be the best strategy to
      triage women with adnexal masses for surgical management. Among postmenopausal
      women, SR +/- SA + CA 125 increased the NRI at a reasonable extra cost. Our data
      do not justify the use of HE4 and ROMA in the initial triage of women with
      adnexal masses. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 27706930
TI  - Bone-site-specific responses to zoledronic acid.
AB  - OBJECTIVES: Bisphosphonates are widely used to treat bone diseases such as
      osteoporosis. However, they may cause osteonecrosis of the jaw. Here, we
      investigated whether in vivo exposure to bisphosphonates has a different effect
      on long bone and jaw osteoclasts, and on the turnover of these different bones.
      MATERIALS AND METHODS: Zoledronic acid (0.5 mg kg-1 weekly) was administered
      intraperitoneally to 3-month-old female mice for up to 6 months. The effects on
      the number of osteoclasts, bone mineralization and bone formation were measured
      in the long bones and in the jaw. RESULTS: Long-term treatment with zoledronic
      acid reduced the number of jaw bone marrow cells, without affecting the number of
      long bone marrow cells. Zoledronic acid treatment did not affect the number of
      osteoclasts in vivo. Yet, the bisphosphonate increased bone volume and mineral
      density of both long bone and jaw. Interestingly, 6 months of treatment
      suppressed bone formation in the long bones without affecting the jaw.
      Unexpectedly, we showed that bisphosphonates can cause molar root resorption,
      mediated by active osteoclasts. CONCLUSIONS: Our findings provide more insight
      into bone-site-specific effects of bisphosphonates and into the aetiology of
      osteonecrosis of the jaw. We demonstrated that bisphosphonates can stimulate
      osteoclast activity at the molar roots.

PMID- 27706931
TI  - Synthetic, Optical and Theoretical Study of Alternating Ethylenedioxythiophene
      Pyridine Oligomers: Evolution from Planar Conjugated to Helicoidal Structure
      towards a Chiral Configuration.
AB  - A series of alternating 3,4-ethylenedioxythiophene-alkynylpyridine oligomers
      (DA)n with increased solubility are synthesized and their photophysical
      properties and nonlinear optical properties are investigated. Their quadratic
      polarizabilities are determined from hyper-Rayleigh scattering experiments to
      obtain information on their conformations in solution. These chromophores, based
      on the alternation of electron-rich (D) and electron-deficient (A) moieties,
      exhibit optical properties that arise from the combination of dipolar and
      helicoidal features in the (DA)n homologue series where n=1-4. The transition
      from dipolar conjugated planar structures (n=1, 2) to helicoidal structures (n=3,
      4) is clearly evidenced by results from symmetry-sensitive second-order nonlinear
      optical experiments. This suggests an approach towards highly efficient chiral
      chromophores for second-order nonlinear optics. Interestingly, this structural
      evolution also has significant impact on the photophysical properties: both
      absorption and fluorescence emission show bathochromic and hyperchromic shifts
      with increasing number of repeating units in the dipolar planar derivatives (n=1
      2) but show saturation effects in the helicoidal structures (n=2-4). In addition,
      the helicoidal structures show sizeable two-photon absorption at 700-750 nm (40
      100 GM) for compounds lacking either electron-donating or electron-withdrawing
      substituents.

PMID- 27706934
TI  - Autonomous Marine Robotic Technology Reveals an Expansive Benthic Bacterial
      Community Relevant to Regional Nitrogen Biogeochemistry.
AB  - Benthic accumulations of filamentous, mat-forming bacteria occur throughout the
      oceans where bisulfide mingles with oxygen or nitrate, providing key but poorly
      quantified linkages between elemental cycles of carbon, nitrogen and sulfur. Here
      we used the autonomous underwater vehicle Sentry to conduct a contiguous, 12.5 km
      photoimaging survey of sea-floor colonies of filamentous bacteria between 80 and
      579 m water depth, spanning the continental shelf to the deep suboxic waters of
      the Santa Barbara Basin (SBB). The survey provided >31 000 images and revealed
      contiguous, white-colored bacterial colonization coating > ~80% of the ocean
      floor and spanning over 1.6 km, between 487 and 523 m water depth. Based on their
      localization within the stratified waters of the SBB we hypothesize a dynamic and
      annular biogeochemical zonation by which the bacteria capitalize on periodic
      flushing events to accumulate and utilize nitrate. Oceanographic time series data
      bracket the imaging survey and indicate rapid and contemporaneous nitrate loss,
      while autonomous capture of microbial communities from the benthic boundary layer
      concurrent with imaging provides possible identities for the responsible
      bacteria. Based on these observations we explore the ecological context of such
      mats and their possible importance in the nitrogen cycle of the SBB.

PMID- 27706933
TI  - Azo-Polymer Janus Particles Assembled by Solvent-Induced Microphase Separation
      and Their Photoresponsive Behavior.
AB  - We report the successful fabrication of photoresponsive Janus particles (JPs)
      composed of an epoxy-based azo polymer and poly(methyl methacrylate) (PMMA). Two
      representative azo polymers, of which one polymer (BP-AZ-CN) has cyano groups as
      electron-withdrawing substituents on the azobenzene moieties and the other
      polymer (BP-AZ-CA) has carboxyl groups as the electron-withdrawing substituents,
      were adopted for the investigation. The nanoscaled JPs, with a narrow size
      distribution and different azo polymer/PMMA ratios, were fabricated through self
      assembly in solution and as dispersions. Upon irradiation with linearly polarized
      light (lambda=488 nm), two types of photoresponsive behavior were observed for
      JPs in the solid state. For JPs composed of BP-AZ-CN and PMMA, the light
      irradiation caused the azo-polymer component to be stretched along the light
      polarization direction. Conversely, for JPs composed of BP-AZ-CA and PMMA, the
      azo-polymer component became separated from PMMA component under the same
      irradiation conditions. These observations are valuable for a deeper
      understanding of the nature of self-assembly and photoinduced mass-transport at
      the nanometer scale.

PMID- 27706935
TI  - London Hybrid Exposure Model: Improving Human Exposure Estimates to NO2 and PM2.5
      in an Urban Setting.
AB  - Here we describe the development of the London Hybrid Exposure Model (LHEM),
      which calculates exposure of the Greater London population to outdoor air
      pollution sources, in-buildings, in-vehicles, and outdoors, using survey data of
      when and where people spend their time. For comparison and to estimate exposure
      misclassification we compared Londoners LHEM exposure with exposure at the
      residential address, a commonly used exposure metric in epidemiological research.
      In 2011, the mean annual LHEM exposure to outdoor sources was estimated to be 37%
      lower for PM2.5 and 63% lower for NO2 than at the residential address. These
      decreased estimates reflect the effects of reduced exposure indoors, the amount
      of time spent indoors (~95%), and the mode and duration of travel in London. We
      find that an individual's exposure to PM2.5 and NO2 outside their residential
      address is highly correlated (Pearson's R of 0.9). In contrast, LHEM exposure
      estimates for PM2.5 and NO2 suggest that the degree of correlation is influenced
      by their exposure in different transport modes. Further development of the LHEM
      has the potential to increase the understanding of exposure error and bias in
      time-series and cohort studies and thus better distinguish the independent
      effects of NO2 and PM2.5.

PMID- 27706936
TI  - Enhanced Mobility of Spin-Helical Dirac Fermions in Disordered 3D Topological
      Insulators.
AB  - The transport length ltr and the mean free path le are determined for bulk and
      surface states in a Bi2Se3 nanoribbon by quantum transport and transconductance
      measurements. We show that the anisotropic scattering of spin-helical Dirac
      fermions results in a strong enhancement of ltr (~ 200 nm) and of the related
      mobility MUtr (~ 4000 cm2 V-1 s-1), which confirms theoretical predictions.1
      Despite strong disorder, the long-range nature of the scattering potential gives
      a large ratio ltr/le ~ 8, likely limited by bulk/surface coupling. This suggests
      that the spin-flip length lsf ~ ltr could reach the micron size in materials with
      a reduced bulk doping and paves the way for building functionalized spintronic
      and ballistic electronic devices out of disordered 3D topological insulators.

PMID- 27706937
TI  - Managing Excitons and Charges for High-Performance Fluorescent White Organic
      Light-Emitting Diodes.
AB  - The simultaneous realization of high efficiency, stable spectra, high color
      rendering index (CRI), and low-efficiency roll-off in a fluorescent white organic
      light-emitting diode (WOLED) still remains a big challenge. Here, we demonstrate
      high-performance conventional fluorescent-dopant-based WOLEDs by strategic
      management of singlet and triplet excitons within an efficient emissive zone.
      This design consists of two separated red/green sub-EMLs with ultralow doping
      concentration and a sandwiched sub-EML doped with red and green fluorescent dyes
      at a relatively high concentration, which can harness all electrogenerated
      excitons and reduce the energy loss to the utmost extent. Accordingly, the
      resulting WOLED realizes an external quantum efficiency (EQE) of 18.2% with a
      maximum power efficiency of 44.6 lm W-1. At the practical luminance of 1000 cd m
      2 for the lighting source, the EQE still remains as high as 16.2% with a CRI of
      82 and stable color spectra. A comprehensive understanding of the device working
      mechanism is performed to guide design of efficient and stable fluorescent
      WOLEDs.

PMID- 27706938
TI  - Bispecific Monoclonal Antibody-based Multi-analyte ELISA for Furaltadone
      Metabolite, Malachite Green and Leucomalachite Green in Aquatic Products.
AB  - A new multi-analyte immunoassay was designed to screen furaltadone metabolite 5
      morpholinomethyl-3-amino-2-oxazolidone (AMOZ), malachite green (MG), and
      leucomalachite green (LMG) in aquatic products using a bispecific monoclonal
      antibody (BsMAb). Gradient drug mutagenesis methods were separately used to
      prepare an anti-3-nitrobenzaldehyde-derivatized AMOZ (3-NPAMOZ) hybridoma cell
      line that was hypoxanthine-guanine-phosphoribosyltransferase (HGRPT) deficient
      and an anti-LMG hybridoma cell line that was thymidine kinase (TK) deficient.
      BsMAb recognizing 3-NPAMOZ and LMG was generated using hybrid-hybridomas of HGRPT
      and TK deficient cell lines. For AMOZ and LMG, respectively, the BsMAb-based
      indirect competitive ELSIA (ic-ELISA) values of 1.7 ng/mL and 45.3 ng/mL and
      detection limits of 0.2 ng/mL and 4.8 ng/mL. To establish the ic-ELISA, 3-NPAMOZ
      derivatized from AMOZ with 3-nitrobenzaldehyde and LMG reduced from MG by
      potassium borohydride was recognized by BsMAb. Recoveries of AMOZ, MG, and LMG in
      aquatic products were satisfactory and correlated with HPLC analysis. Thus, the
      multi-analyte ic-ELISA is suitable for rapid quantification of AMOZ, MG and LMG
      in aquatic products.

PMID- 27706932
TI  - Do specific NMDA receptor subunits act as gateways for addictive behaviors?
AB  - Addiction to alcohol and drugs is a major social and economic problem, and there
      is considerable interest in understanding the molecular mechanisms that promote
      addictive drives. A number of proteins have been identified that contribute to
      expression of addictive behaviors. NMDA receptors (NMDARs), a subclass of
      ionotropic glutamate receptors, have been of particular interest because their
      physiological properties make them an attractive candidate for gating induction
      of synaptic plasticity, a molecular change thought to mediate learning and
      memory. NMDARs are generally inactive at the hyperpolarized resting potentials of
      many neurons. However, given sufficient depolarization, NMDARs are activated and
      exhibit long-lasting currents with significant calcium permeability. Also, in
      addition to stimulating neurons by direct depolarization, NMDARs and their
      calcium signaling can allow strong and/or synchronized inputs to produce long
      term changes in other molecules (such as AMPA-type glutamate receptors) which can
      last from days to years, binding internal and external stimuli in a long-term
      memory trace. Such memories could allow salient drug-related stimuli to exert
      strong control over future behaviors and thus promote addictive drives. Finally,
      NMDARs may themselves undergo plasticity, which can alter subsequent neuronal
      stimulation and/or the ability to induce plasticity. This review will address
      recent and past findings suggesting that NMDAR activity promotes drug- and
      alcohol-related behaviors, with a particular focus on GluN2B subunits as possible
      central regulators of many addictive behaviors, as well as newer studies
      examining the importance of non-canonical NMDAR subunits and endogenous NMDAR
      cofactors.

PMID- 27706940
TI  - Direct Observation of Electron-Phonon Coupling and Slow Vibrational Relaxation in
      Organic-Inorganic Hybrid Perovskites.
AB  - Quantum and dielectric confinement effects in 2D hybrid perovskites create
      excitons with a binding energy exceeding 150 meV. We exploit the large exciton
      binding energy to study exciton and carrier dynamics as well as electron-phonon
      coupling in hybrid perovskites using absorption and photoluminescence (PL)
      spectroscopies. At temperatures below 75 K, we resolve splitting of the excitonic
      absorption and PL into multiple regularly-spaced resonances every 40-46 meV,
      consistent with electron-phonon coupling to phonons located on the organic
      cation. We also resolve resonances with a 14 meV spacing, in accord with coupling
      to phonons with mixed organic and inorganic character, and these assignments are
      supported by density-functional theory calculations. Hot exciton PL and time
      resolved PL measurements show that vibrational relaxation occurs on a picosecond
      timescale competitive with that for PL. At temperatures above 75 K, excitonic
      absorption and PL exhibit homogeneous broadening. While absorption remains
      homogeneous, PL becomes inhomogeneous below 75K, which we speculate is caused by
      the formation and subsequent dynamics of a polaronic exciton.

PMID- 27706939
TI  - Nickel-Catalyzed Cross-Electrophile Coupling of Alkyl Fluorides: Stereospecific
      Synthesis of Vinylcyclopropanes.
AB  - The stereospecific reductive cross-electrophile coupling reaction of 2-vinyl-4
      halotetrahydropyrans for vinylcyclopropane synthesis is reported. The nickel
      catalyzed reaction occurs with both alkyl fluorides and alkyl chlorides. To the
      best of our knowledge, this is the first reported cross-electrophile coupling
      reaction of an alkyl fluoride. Ring contraction proceeds with high
      stereospecificity, providing selective synthesis of either diastereomer of di-
      and trisubstituted cyclopropanes. The utility of this methodology is demonstrated
      by several synthetic applications including the synthesis of the natural product
      dictyopterene A. 2-Vinyl-4-fluorotetrahydrofurans also undergo stereospecific
      ring contractions, providing access to synthetically useful hydroxymethyl
      cyclopropanes.

PMID- 27706941
TI  - Mild and Selective Mono-Iodination of Unprotected Peptides as Initial Step for
      the Synthesis of Bioimaging Probes.
AB  - Chemoselective functionalization of peptides and proteins to selectively
      introduce residues for detection, capture, or specific derivatization is of high
      interest to the synthetic community. Here we report a new method for the mild and
      effective mono-iodination of tyrosine residues in fully unprotected peptides.
      This method is highly chemoselective and compatible with a wide variety of
      functional groups. The introduced iodine can subsequently serve as a handle for
      further functionalization such as introduction of fluorescent dyes and thus be
      used for chemoselective labeling of isolated peptides.

PMID- 27706942
TI  - How to Increase the Signal-to-Noise Ratio of Graphene Oxide Membrane Research.

PMID- 27706943
TI  - Spotlights: Volume 7, Issue 19.

PMID- 27706945
TI  - The role of MIF, cyclinD1 and ERK in the development of pulmonary hypertension in
      broilers.
AB  - Pulmonary hypertension (PH) is a major disease in the broiler breeding industry.
      During PH, the pulmonary artery undergoes remodelling, which is caused by
      pulmonary vascular smooth muscle cell proliferation. CyclinD1 regulates cell
      proliferation. This study investigated the role of cyclinD1 in the development of
      PH in broilers, and which bioactivators and signalling pathway are involved in
      the pathological process. The PH group contained 3-4-week-old broilers with
      clinical PH, and the healthy group broilers from the same flock without PH.
      Histopathology indicated pulmonary arterial walls were thicker in the PH group
      compared with the healthy group. Target gene expressions of macrophage migration
      inhibitory factor (MIF), extracellular signal-regulated kinase (ERK), and
      cyclinD1 detected by quantitative real-time PCR were upregulated in the PH group
      compared with the healthy group. Immunohistochemistry showed MIF, phosphorylated
      ERK (p-ERK) and cyclinD1 were present on pulmonary vascular walls; MIF was
      present in the cytoplasm of arterial endothelial cells and smooth muscle cells; p
      ERK and cyclinD1 were present in smooth muscle cell cytoplasm. Western blotting
      demonstrated that MIF, p-ERKand cyclinD1 levels were significantly higher (P <
      0.01) in the PH group compared with the healthy group. In summary, increased MIF
      in PH broiler pulmonary arteries upregulated cyclinD1 via the ERK signalling
      pathway to induce pulmonary vascular smooth muscle cell proliferation, causing
      pulmonary artery remodelling and hypertension.

PMID- 27706944
TI  - Phytochemical Inhibition of Multidrug Resistance Protein-1 as a Therapeutic
      Strategy for Hemangioendothelioma.
AB  - AIMS: Hemangiomas are endothelial cell tumors and the most common soft tissue
      tumors in infants. They frequently cause deformity and can cause death. Current
      pharmacologic therapies have high-risk side-effect profiles, which limit the
      number of children who receive treatment. The objectives of this work were to
      identify the mechanisms through which standardized berry extracts can inhibit
      endothelial cell tumor growth and test these findings in vivo. RESULTS: EOMA
      cells are a validated model that generates endothelial cell tumors when injected
      subcutaneously into syngeneic (129P/3) mice. EOMA cells treated with a blend of
      powdered natural berry extracts (NBE) significantly inhibited activity of
      multidrug resistance protein-1 (MRP-1) compared to vehicle controls. This
      resulted in nuclear accumulation of oxidized glutathione (GSSG) and apoptotic
      EOMA cell death. When NBE-treated EOMA cells were injected into mice, they
      generated smaller tumors and had a higher incidence of apoptotic cell death
      compared to vehicle-treated EOMA cells as demonstrated by immunocytochemistry.
      Kaplan-Meier survival curves for tumor-bearing mice showed that NBE treatment
      significantly prolonged survival compared to vehicle-treated controls.
      INNOVATION: These are the first reported results to show that berry extracts can
      inhibit MRP-1 function that causes apoptotic tumor cell death by accumulation of
      GSSG in the nucleus of EOMA cells where NADPH oxidase is hyperactive and causes
      pathological angiogenesis. CONCLUSIONS: These findings indicate that berry
      extract inhibition of MRP-1 merits consideration and further investigation as a
      therapeutic intervention and may have application for other cancers with elevated
      MRP-1 activity. Antioxid. Redox Signal. 26, 1009-1019.

PMID- 27706946
TI  - Stereotactic ablative body radiotherapy for non-small-cell lung cancer: setup
      reproducibility with novel arms-down immobilization.
AB  - OBJECTIVE: A clinical evaluation of the intrafraction and interfraction setup
      accuracy of a novel thermoplastic mould immobilization device and patient
      position in early-stage lung cancer being treated with stereotactic radiotherapy
      at the Beatson West of Scotland Cancer Centre, Glasgow, UK. METHODS: 35 patients
      were immobilized in a novel, arms-down position, with a four-point KlarityTM
      (Klarity Medical Products, Ohio, US) clear thermoplastic mould fixed to a SinMed
      (CIVCO Medical solutions, lowa, US) head and neck board. A knee support was also
      used for patient comfort and support. Pre- and post-treatment kilovoltage cone
      beam CT (CBCT) images were fused with the planning CT scan to determine intra-
      and interfraction motion. A total of 175 CBCT scans were analysed in the
      longitudinal, vertical and lateral directions. RESULTS: The mean intrafraction
      errors were 0.05 +/- 0.77 mm (lateral), 0.44 +/- 1.2 mm (superior-inferior) and 
      1.44 +/- 1.35 mm (anteroposterior), respectively. Mean composite three
      dimensional displacement vector was 2.14 +/- 1.2 mm. Interfraction errors were 
      0.66 +/- 2.35 mm (lateral), -0.13 +/- 3.11 mm (superior-inferior) and 0.00 +/-
      2.94 mm (anteroposterior), with three-dimensional vector 4.08 +/- 2.73 mm.
      CONCLUSION: Setup accuracy for lung image-guided stereotactic ablative
      radiotherapy using a unique immobilization device, where patients have arms by
      their sides, has been shown to be safe and favourably comparable to other
      published setup data where more complex and cumbersome devices were utilised.
      There was no arm toxicity reported and low arm doses. Advances in knowledge: We
      report on the accuracy of a novel patient immobilization device.

PMID- 27706947
TI  - Simultaneous integrated boost (SIB) of the parametrium and cervix in radiotherapy
      for uterine cervical carcinoma: a dosimetric study using a new alternative
      approach.
AB  - OBJECTIVE: To compare the dose distributions of intensity-modulated radiotherapy
      (IMRT) and volumetric-modulated arc therapy (VMAT) using the simultaneous
      integrated boost (SIB) technique with that of the traditional midline block (MB)
      technique for boosting the parametrium in patients with cervical cancer. METHODS:
      Treatment plans using VMAT or IMRT with the SIB technique (VMAT-SIB and IMRT-SIB)
      and IMRT followed by the MB technique (IMRT-MB) were generated for each of the 10
      patients with cervical cancer. For the SIB plans, 45-Gy and 50-Gy dose levels in
      25 equal fractions were set for the pelvis planning target volume 45 (PTV45) and
      the parametrial boost volume (PTV50), respectively. For the IMRT-MB plans, the
      parametrium was sequentially boosted with the MB technique (5.4 Gy in three
      fractions) after pelvic IMRT (PTV45). RESULTS: Volume receiving 100% of the
      prescribed dose or more coverage of the PTV50 was significantly better for VMAT
      SIB and IMRT-SIB than that for IMRT-MB (99.08 and 99.31% compared with 91.79%,
      respectively; p < 0.05). VMAT-SIB and IMRT-SIB both generated significantly
      greater doses to the organs at risk (OARs) except for the volume receiving 50 Gy
      or more doses, which were significantly lower for the bladder and bowel.
      Comparable results were achieved with VMAT-SIB and IMRT-SIB. CONCLUSION: The VMAT
      SIB and IMRT-SIB techniques are promising in terms of dose distributions and
      tumour coverage, although these approaches might result in slightly higher doses
      of radiation to the OARs. Advances in knowledge: This is the first study to
      examine the feasibility of the SIB technique using IMRT or VMAT to boost the
      parametrium. The techniques dosimetrically produced better target coverage but
      resulted in slightly higher doses to the OARs.

PMID- 27706948
TI  - Which Should be Preferred for Moderate-Size Kidney Stones? Ultramini Percutaneous
      Nephrolithotomy or Retrograde Intrarenal Surgery?
AB  - PURPOSE: Comparison of effectiveness and safety of ultramini percutaneous
      nephrolithotomy (UMPNL) and retrograde intrarenal surgery (RIRS) in treatment of
      moderate-sized renal stones. MATERIAL AND METHODS: The patients scheduled for
      surgery attributable to renal stones with the greatest diameter of 10 to 25 mm
      were prospectively analyzed. Patients were randomized into groups with tossing a
      coin method. The patients who had UMPNL and RIRS were defined as Group I and
      Group II, respectively. The groups were compared for demograhic data, stone
      characteristics, operative and postoperative data, stone-free status, and the
      complications. Student's t-test and Pearson's Chi square tests were used for
      statistical analysis. p < 0.05 was considered as statistically significant.
      RESULTS: There were 30 patients in Group I, and 43 patients in Group II. The
      groups were similar for age, gender, side of the stone, and surface area
      characteristics of the stone (p = 0.194, p = 0.470, p = 0.990, and p = 0.487,
      respectively). Stone-free rate was 80% (n = 24) in UMPNL, and 74.4% (n = 32) in
      RIRS (p = 0.579). Modified Clavien Classification Grade 1 to 2 and 3A to 3B
      complications were similar in two groups (p = 0.959 and p = 0.192, respectively).
      Comparison of stone-free rates was 93.3% in UMPNL, and 42.9% in RIRS groups for
      lower pole stones (p = 0.009). Groups I and II were significantly different for
      visual analog scale scores for postoperative pain (4.73 +/- 1.25 vs 2.30 +/-
      1.12), hospital stay (2.46 +/- 3.02 vs 1.37 +/- 1.48 days), and time to return to
      normal daily life (11.26 +/- 5.55 vs 6.65 +/- 4.30 days) (p < 0.001, p < 0.001,
      and p < 0.001, respectively). CONCLUSION: Both UMPNL and RIRS procedures are
      effective and safe methods in treatment of middle-sized renal stones. However,
      UMPNL is more effective than RIRS in treatment of lower pole stones. RIRS is more
      advantageous when loss from work is taken into consideration.

PMID- 27706949
TI  - Age-related racial disparities in prostate cancer patients: A systematic review.
AB  - OBJECTIVE: Prostate cancer mortality rates have decreased over recent decades,
      but racial disparities in prostate cancer survival still present as a serious
      challenge. These disparities may be impacted by age; in fact, African-American
      men younger than age 65 have prostate cancer mortality rates nearly three times
      greater than that of White men. Therefore, a systematic literature review was
      conducted in Medline and EMBASE databases focusing on articles comparing survival
      and mortality rates for prostate cancer patients across age and race. DESIGN:
      Articles included were based on the following criteria: (1) included African
      American and White prostate cancer patients residing in the US; (2) measured
      racial disparities across distinct age categories with at least one category
      below and one above age 65; and (3) addressed racial disparities in terms of
      overall survival or mortality. RESULTS: Twenty eight articles compared survival
      and mortality disparities between African-American and White prostate cancer
      patients across different age categories. Of the 28 articles, 19 articles (68%)
      showed disparities decreased with age, 8 articles (29%) showed disparities
      constant with age, and 1 article (3%) showed disparities increased with age.
      CONCLUSIONS: More often the survival and mortality gap between African-American
      and White prostate cancer patients decreases with age. Additional studies are
      needed to elucidate other factors that may influence racial disparities in
      prostate cancer patients. These results provide insight into the racial
      disparities in prostate cancer and suggest more resources should be directed
      towards decreasing the disparity gap in younger prostate cancer patients.

PMID- 27706950
TI  - Deep inspiration breath-hold radiotherapy for lung cancer: impact on image
      quality and registration uncertainty in cone beam CT image guidance.
AB  - OBJECTIVE: We investigated the impact of deep inspiration breath-hold (DIBH) and
      tumour baseline shifts on image quality and registration uncertainty in image
      guided DIBH radiotherapy (RT) for locally advanced lung cancer. METHODS: Patients
      treated with daily cone beam CT (CBCT)-guided free-breathing (FB) RT had an
      additional CBCT in DIBH at three fractions. These CBCT scans were offline rigidly
      registered (on tumour) to FB and DIBH CT scans acquired at planning. All
      registrations were repeated to evaluate the intraobserver uncertainty. CBCT scans
      were scored on degree of streak artefacts and visualization of tumour and
      anatomical structures. We examined the impact of tumour baseline shift between
      consecutive DIBHs on CBCT image quality. RESULTS: CBCT scans from 15 patients
      were analysed. Intraobserver image registration uncertainty was approximately 2
      mm in both FB and DIBH, except for the craniocaudal direction in FB, where it was
      >3 mm. On the 31st fraction, the intraobserver uncertainty increased compared
      with the second fraction. This increase was more pronounced in FB. Image quality
      scores improved in DIBH compared with FB for all parameters in all patients.
      Simulated tumour baseline shifts <=2 mm did not affect the CBCT image quality
      considerably. CONCLUSION: DIBH CBCT improved image quality and reduced
      registration uncertainty in the craniocaudal direction in image-guided RT of
      locally advanced lung cancer. Baseline shifts <=2 mm in DIBH during CBCT
      acquisition did not affect image quality. Advances in knowledge: DIBH RT has
      dosimetric advantages over FB; this work demonstrates an additional benefit of
      DIBH in terms of registration accuracy because of improved image quality.

PMID- 27706951
TI  - Inhibition of pancreatic lipase and amylase by extracts of different spices and
      plants.
AB  - The aim of this study is to search new anti-obesity and anti-diabetic agents from
      plant and spices crude extracts as alternative to synthetic drugs. The inhibitory
      effect of 72 extracts was evaluated, in vitro, on lipase and amylase activities.
      Aqueous extracts of cinnamon and black tea exhibited an appreciable inhibitory
      effect on pancreatic amylase with IC50 values of 18 and 87 MUg, respectively.
      Aqueous extracts of cinnamon and mint showed strong inhibitory effects against
      pancreatic lipase with IC50 of 45 and 62 MUg, respectively. The presence of bile
      salts and colipase or an excess of interface failed to restore the lipase
      activity. Therefore, the inhibition of pancreatic lipase, by extracts of spices
      and plants, belongs to an irreversible inhibition. Crude extract of cinnamon
      showed the strongest anti-lipase and anti-amylase activities which offer a
      prospective therapeutic approach for the management of diabetes and obesity.

PMID- 27706952
TI  - Authors' response to Finkelstein's letter to the editor regarding our recent
      review of ambient airborne asbestos concentrations (Abelmann et al., 2015).

PMID- 27706953
TI  - Foam cell formation by particulate matter (PM) exposure: a review.
AB  - Increasing evidence suggests that exposure of particulate matter (PM) from
      traffic vehicles, e.g., diesel exhaust particles (DEP), was associated with
      adverse vascular effects, e.g., acceleration of atherosclerotic plaque
      progression. By analogy, engineered nanoparticles (NPs) could also induce similar
      effects. The formation of lipid laden foam cells, derived predominately from
      macrophages and vascular smooth muscle cells (VSMC), is closely associated with
      the development of atherosclerosis and adverse vascular effects. We reviewed
      current studies about particle exposure-induced lipid laden foam cell formation.
      In vivo studies using animal models have shown that exposure of air pollution by
      PM promoted lipid accumulation in alveolar macrophages or foam cells in plaques,
      which was likely associated with pulmonary inflammation or systemic oxidative
      stress, but not blood lipid profile. In support of these findings, in vitro
      studies showed that direct exposure of cultured macrophages to DEP or NP
      exposure, with or without further exposure to external lipids, promoted
      intracellular lipid accumulation. The mechanisms remained unknown. Although a
      number studies found increased reactive oxygen species (ROS) or an adaptive
      response to oxidative stress, the exact role of oxidative stress in mediating
      particle-induced foam cell formation requires future research. There is currently
      lack of reports concerning VSMC as a source for foam cells induced by particle
      exposure. In the future, it is necessary to explore the role of foam cell
      formation in particle exposure-induced atherosclerosis development. In addition,
      the formation of VSMC derived foam cells by particle exposure may also need
      extensive studies.

PMID- 27706954
TI  - Sexual functioning and quality of life of Hong Kong Chinese women with
      infertility problem.
AB  - Infertility is estimated to affect 10-15% of couples in industrialized countries
      and many of them are under tremendous stress. Stress can lead to poor quality of
      life and sexual dysfunction in general, but little is known about their
      prevalence in infertile women. We, therefore, conducted this cross-sectional
      survey in two primary care subfertility clinics between August 2012 and April
      2013. A total of 159 women completed two validated Chinese questionnaires: Female
      Sexual Function Index and core Fertility Quality of Life. The overall Female
      Sexual Function Index score (mean +/- SD) of the whole group was 24.99 +/- 4.22.
      Using the urban Chinese cut-off, the prevalence of female sexual dysfunction, low
      desire, arousal disorder, lubrication disorder, orgasmic disorder and sexual pain
      were 32.5%, 15.7%, 19.3%, 22.3%, 33.1% and 15.1%. The core Fertility Quality of
      Life score of the whole group was 59.76 +/- 13.59 and the subgroup of infertile
      women with sexual dysfunction (n = 50) had significantly lower mean core
      Fertility Quality of Life score than those without sexual dysfunction (n = 109)
      (55.03 versus 61.88) (p = 0.005). Among the subscales, the relational score had
      the strongest correlation with sexual dysfunction. Infertile women with sexual
      dysfunction had significantly worse quality of life especially in the relational
      aspect.

PMID- 27706957
TI  - ?
AB  - Tour deforce: Scotland's chief nursing office Anne Jarviefarleft) has spent a
      week touring hospitals and other healthcare facilitiesin Tayside to promote
      nursing and mid wifery as a casreer. The tour entitled From Primary Care rector
      of nursing Elizabeth Wilson (far right). Ms Wilson said the tour offered staff a
      chance to 'pay tribute' to Ms Jarvie before she retires next year.

PMID- 27706955
TI  - Salt and obesity: a systematic review and meta-analysis of observational studies.
AB  - BACKGROUND: Existing research has investigated the association between sodium
      intake and obesity. We aim to conduct a systematic review and meta-analysis of
      reported evidence regarding the association between sodium intake and obesity.
      METHODS: Multiple electronic databases (PubMed, Scopus, and Google Scholar) were
      searched for observational studies published until August 2016. A systematic
      literature review identified 11 cohort and 21 cross-sectional studies. RESULT:
      Among the 32 studies identified in the systematic literature search, only 18
      cross-sectional reports had sufficient data to be included in the meta-analysis.
      Higher sodium consumption was associated with greater BMI (weighed mean
      difference (WMD) = 1.24 kg/m2, 95%CI: 0.80, 1.67; I2 = 98.4%; p < .0001), and
      higher sodium intake was associated with 4.75 cm (95%CI: 3.25, 6.25; 90.8%; p
      <.0001) greater waist circumference (WC). CONCLUSION: The present meta-analysis
      suggests that sodium consumption was associated with greater BMI and WC.

PMID- 27706956
TI  - A comparative assessment of the acute inhalation toxicity of vanadium compounds.
AB  - Vanadium compounds have become important in industrial processes, resulting in
      workplace exposure potential and are present in ambient air as a result of fossil
      fuel combustion. A series of acute nose-only inhalation toxicity studies was
      conducted in both rats and mice in order to obtain comparative data on the acute
      toxicity potential of compounds used commercially. V2O3, V2O4, and V2O5, which
      have different oxidation states (+3, +4, +5, respectively), were delivered as
      micronized powders; the highly water-soluble and hygroscopic VOSO4 (+4) could not
      be micronized and was instead delivered as a liquid aerosol from an aqueous
      solution. V2O5 was the most acutely toxic micronized powder in both species.
      Despite its lower overall percentage vanadium content, a liquid aerosol of VOSO4
      was more toxic than the V2O5 particles in mice, but not in rats. These data
      suggest that an interaction of characteristics, i.e., bioavailability, solubility
      and oxidation state, as well as species sensitivity, likely affect the toxicity
      potential of vanadium compounds. Based on clinical observations and gross
      necropsy findings, the lung appeared to be the target organ for all compounds.
      The level of hazard posed will depend on the specific chemical form of the
      vanadium. Future work to define the inhalation toxicity potential of vanadium
      compounds of various oxidation states after repeated exposures will be important
      in understanding how the physico-chemical and biological characteristics of
      specific vanadium compounds interact to affect toxicity potential and the
      potential risks posed to human health.

PMID- 27706958
TI  - Vantage point.
AB  - 'DIVIDED BY our common language.' So said George Bernard Shaw about relationships
      between America and Britain.

PMID- 27706959
TI  - Senior staff pay system delayed RCN fellowship awards.
AB  - The government has delayed the introduction of a new pay system for health
      service managers after professional organisations raised concerns particularly
      over the tight timetable.

PMID- 27706960
TI  - Warning over EU recruitment 'challenges'.
AB  - Nursing managers have been warned that they will face recruitment 'challenges'
      next year when the latest 'accession countries' join the European Union.

PMID- 27706961
TI  - Nurses face change barriers.
AB  - The RCN clinical leadership programme is to look at the hurdles nurses must
      overcome when trying to implement leadership skills at work.

PMID- 27706963
TI  - RCN welcomes 'promise' onfoundation trust boards.
AB  - The RCN has welcomed a government announcement that it believes confirms that
      nurses 'will have places on the board of directors' in foundation trusts.

PMID- 27706962
TI  - Editorial.
AB  - Getting nurses to speak up about their work and profession has always been a
      challenge. Some argue it is to do with nursing being a female profession. Others
      believe it is due to nurses working in and adopting a culture that discourages
      'speaking up'. A third school of thought is that nursing is so simple that there
      is nothing special to say about it. It is no consolation to know that it is a
      global problem; nurses all over the world seem to have difficulty explaining why
      what they do is so important.

PMID- 27706964
TI  - Conferences.

PMID- 27706965
TI  - On the move round up.
AB  - Promotions / new appointments.

PMID- 27706966
TI  - Sky's the limit.
AB  - MEETING GROUP Captain Annie Reid, Matron-in-Chief for The Princess Mary's Royal
      Air Force Nursing Service (PMRAFNS), challenges many expectations about such a
      person. She is not 'posh' or stuffy, but down to earth and her Cornish accent
      gives her speech sincerity and homeliness. Walking with her across the base where
      she is stationed and where I am to interview her, she is saluted at regular
      intervals, reflecting her senior position, but each of her salutes is followed by
      a comment of concern about the individual she meets.

PMID- 27706967
TI  - Just another day in the office.
AB  - John is lying on the bed, earphones on and listening to Johnny Dankworth. He is
      immobilised because of a fractured femur, the result of a push down the stairs
      from someone he had thought was a friend.

PMID- 27706969
TI  - Nurse nurse.

PMID- 27706968
TI  - webscan.

PMID- 27706971
TI  - Breaking Through leadership initiative to benefit hundreds.
AB  - Hundreds of NHS staff from black and minority ethnic (BME) backgrounds are to
      undertake a dedicated leadership training programme over the next 18 months.

PMID- 27706970
TI  - RCN fellowship awards.
AB  - Nursing Management editorial adviser David Benton (pictured) was among four UK
      nurses who officially received RCN fellowships at the college annual general
      meeting last month. Mr Benton was awarded the honour for 'his outstanding
      contribution to nursing and health policy'.

PMID- 27706972
TI  - Investing in people.
AB  - PEOPLE ARE the greatest asset of any organisation - private, public, voluntary or
      academic. What does it take to attract, retain and grow people so they are
      successful members of the team? Health care is no different from any other
      enterprise - everyone from chief executives to first-level managers is under
      constant pressure to reduce costs and maximise performance.

PMID- 27706973
TI  - Leading the way.
AB  - LIKE MANY people who prove themselves in responsible roles, Maureen Naughton,
      chief nurse at Leeds Teaching Hospitals NHS Trust, has developed her position to
      reflect her personal qualities and the demands of an increasingly complex job.

PMID- 27706975
TI  - Conferences.
AB  - Venue: National Exhibition Centre, Birmingham Delegates can pick and mix from six
      programmes; recruitment, retention, performance management, training and
      education, people management and employment law. Workshops focus on topics such
      as management skills, interview skills and personal development.

PMID- 27706974
TI  - The challenge of governance in nursing.
AB  - I DON'T KNOW if it is a boy's thing but, growing up in the second half of the
      20th century, the great crime figures we learned about were Jack the Ripper, Haig
      the acid-bath murderer and Crippen. For any youngster in the first half of the
      21st century, probably the single name that will be on everyone's lips is Harold
      Shipman. His will be a substantial legacy.

PMID- 27706976
TI  - Editorial.
AB  - For more than two years, Nursing Management has been carrying reports from nurses
      in the field about the problems facing patients in the elderly care sector.
      Changes in funding arrangements and increased pressure on both the NHS and local
      authorities to facilitate speedier discharge represents a double bind that is
      sure to cause difficulties for older patients. Following reports in February from
      the National Audit Office (NAO) and the King's Fund we now have evidence of the
      extent of the problem.

PMID- 27706978
TI  - Questioning qualifications.
AB  - VIRGINIA, DEBBIE AND AGNES all have two years' nurse training. All of them
      trained abroad and recently came to the UK. Virginia is a deputy manager in a
      nursing home; because they cannot register, Debbie and Agnes are working as care
      assistants.

PMID- 27706977
TI  - Trusts urged to plan for earlier discharges.
AB  - The National Audit Office (NAO) has urged trusts to start discharge planning
      earlier and to do more to assess the care path-ways of elderly patients.

PMID- 27706979
TI  - Staff survey closes.
AB  - Healthcare professionals across England have until the end of this month to
      complete their NHS survey questionnaires about how well they are managed.

PMID- 27706981
TI  - Patient choice to refocus managers.
AB  - An expansion of the government scheme to give patients more choice is expected to
      force nursing managers to focus on patient, rather than organisational, needs.

PMID- 27706980
TI  - Nursing programme director steps down in NHS shake-up.
AB  - Jean Faugier steps down as director of the NHS national nursing leadership pro-
      gramme this month as part of an ongoing shake-up of the NHS leadership centre.

PMID- 27706982
TI  - Practice nurses may swap employers.
AB  - Community nurse managers can anticipate a potential increase in the number of
      practice nurses wanting to be employed by NHS primary care organisations.

PMID- 27706985
TI  - Support systems.
AB  - CLINICAL SUPERVISION is variously regarded as a lifeline, an intrusion or an
      irrelevance. When done well, it can enhance and improve your practice and develop
      your career. But it is also a much misunderstood and confused concept.

PMID- 27706984
TI  - Foundation status divides senior nurses.
AB  - Senior nurses at three-star trusts remain divided over the benefits of gaining
      foundation status despite government efforts to push ahead with the initiative
      this spring.

PMID- 27706986
TI  - PLAY YOUR CARDS RIGHT mental health care at home.
AB  - THE CRISIS Assessment and Rapid Domiciliary Support (CARDS) team in Southport was
      set up in response to the National Service Framework for Mental Health ( DoH 1999
      ). It was one of the first crisis resolution and home treatment teams to be
      developed.

PMID- 27706988
TI  - Webscan.

PMID- 27706987
TI  - ?
AB  - Opportunities for communication form an important part of the experience of
      living in a nursing home. This American study was based upon a detailed analysis
      of the telephone calls made by three female residents from two nursing homes over
      a period of seven days. The total conversation time recorded during this period
      was 56 minutes. The transcripts revealed a range of topics being discussed, such
      as domestic skills, the weather and travel. Humour was a prominent aspect of the
      conversations. The researchers concluded that the telephone appeared to be a
      vital communication link between residents and their family and friends. 15
      references.

PMID- 27706989
TI  - Under cover.
AB  - WHETHER YOU read this delightful book for advice, tips or simply pleasure, I am
      sure you will remember its key messages and apply them to your working
      environment.

PMID- 27706990
TI  - Violence and aggression in the workplace Paul Linsley Violence and aggression in
      the workplace Radcliffe First 160 L21.95 1 85775 784 185775784 [Formula: see
      text].
AB  - IN RECENT YEARS, the number of aggressive and violent acts perpetrated on
      healthcare workers has risen, despite the launch of various 'zero tolerance'
      campaigns.

PMID- 27706991
TI  - New year's honours.
AB  - Former RCN president Roswyn Hakesley-Brown (left) headed the list of nurses
      featured in the New Year's honours list this month. Ms Hakesley-Brown was made a
      CBE for services to health care.

PMID- 27706992
TI  - Conferences.

PMID- 27706994
TI  - Have your say.

PMID- 27706993
TI  - 'Shake up' for code of professional conduct.
AB  - The Nursing and Midwifery Council (NMC) this month officially launches proposals
      to 'shake up' the nursing and mid-wifery code of professional conduct.

PMID- 27706996
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27706995
TI  - Leadership fellow awards.
AB  - Three senior nurses are among the latest care professionals to have received The
      Health Foundation leadership fellows award.

PMID- 27706997
TI  - Get connected.
AB  - ONE OF THE latest announcements from NHS Connecting for Health (CfH) is that it
      is devolving the National Programme for Information Technology (NPfIT) to local
      trusts, as part of the so-called NPfIT Local Ownership Programme, which is
      described in The NHS in England: The operating framework for 2007/08.

PMID- 27706999
TI  - ?
AB  - I AM OFTEN struck by the ability of nurses to combined the delivery of good
      patient care with the management of change, especially when they succeed in this
      against the odds.

PMID- 27707000
TI  - Betraying the NHS: Health abandoned Michael Mandelstam Betraying the NHS: Health
      abandoned Jessica Kingsley First 317 L14.99 1 84310 482 2 1843104822 [Formula:
      see text].
AB  - THIS BOOK records what has been happening to the NHS during 2005/06 by focusing
      on events in the West Suffolk area, where closure of local rehabilitation
      services has affected above all those who are most vulnerable and have the most
      complex needs.

PMID- 27707001
TI  - Comparison of simultaneous and sequential administration of fentanyl-propofol for
      surgical abortion: a randomized single-blinded controlled trial.
AB  - Propofol lipid emulsion (PLE) is a nanosized sedative, and it is used with a
      combination of salted antalgic prodrug, fentanyl citrate (FC). To illustrate the
      synergistic effect of mixing, we compared the sedation/analgesia resulting from
      simultaneous and sequential administration in surgically induced abortion (No.
      ChiCTR-IPC-15006153). Simultaneous group showed lower bispectral index, blood
      pressure, and heart rate, when cannula was inserted into the uterus. It also
      showed less frequency of hypertension, sinus tachycardia, movement, pain at the
      injection site, and additional FC. Therefore, premixing of PLE and FC enhanced
      the sedation and analgesia; stabilized the hemodynamics; lessened the incidence
      of movement and injection pain; and reduced the requirement of drugs.

PMID- 27707002
TI  - A new formulation of slight compressibility for arterial tissue and its Finite
      Element implementation.
AB  - In order to avoid the numerical difficulties in locally enforcing the
      incompressibility constraint using the displacement formulation of the Finite
      Element Method, slight compressibility is typically assumed when simulating the
      mechanical response of arterial tissue. The current standard method of accounting
      for slight compressibility of hyperelastic soft tissue assumes an additive
      decomposition of the strain-energy function into a volumetric and a deviatoric
      part. This has been shown, however, to be inconsistent with the linear theory and
      results in cubes retaining their cuboid shape under hydrostatic tension and
      compression, which seems at variance with the reinforcement of arterial tissue
      with two families of collagen fibres. A remedy for these defects is proposed
      here, a solution which generalises the current standard model of slight
      compressibility to include two additional terms, one of which is quadratic in the
      [Formula: see text] invariants and the other quadratic in [Formula: see text].
      Experimental data are used to motivate typical values for the associated material
      constants of these additional terms. Some simulations are performed to allow
      contrasts and comparisons to be made between the current standard model of slight
      compressibility and its generalisation proposed here.

PMID- 27707003
TI  - Non-halogenated new sesquiterpenes from Bornean Laurencia snackeyi.
AB  - Two new non-halogenated sesquiterpenes, snakeol (1) and snakediol (2) were
      isolated together with 9 known sesquiterpenes such as (R,Z)-33-dimethyl-5
      methylene-4-(3-methylpenta-24-dien-1-yl)cyclohex-1-ene (3), palisol (4),
      pacifigorgiol (5), palisadin D (6), palisadin A (7), palisadin B (8), 5
      acetoxypalisadin B (9), debromolaurinterol (10) and alpha-bromocuparane (11) from
      the red algae Laurencia snackeyi. The structures of two new metabolites were
      determined from their spectroscopic data (IR, 1D and 2D NMR and MS). Compounds 1,
      2, 10 and 11 showed strong antibacterial activity against selected human clinical
      bacterial pathogens.

PMID- 27707004
TI  - N-tuple topological/geometric cutoffs for 3D N-linear algebraic molecular
      codifications: variability, linear independence and QSAR analysis.
AB  - Novel N-tuple topological/geometric cutoffs to consider specific inter-atomic
      relations in the QuBiLS-MIDAS framework are introduced in this manuscript. These
      molecular cutoffs permit the taking into account of relations between more than
      two atoms by using (dis-)similarity multi-metrics and the concepts related with
      topological and Euclidean-geometric distances. To this end, the kth two-, three-
      and four-tuple topological and geometric neighbourhood quotient (NQ) total (or
      local-fragment) spatial-(dis)similarity matrices are defined, to represent 3D
      information corresponding to the relations between two, three and four atoms of
      the molecular structures that satisfy certain cutoff criteria. First, an analysis
      of a diverse chemical space for the most common values of topological/Euclidean
      geometric distances, bond/dihedral angles, triangle/quadrilateral perimeters,
      triangle area and volume was performed in order to determine the intervals to
      take into account in the cutoff procedures. A variability analysis based on
      Shannon's entropy reveals that better distribution patterns are attained with the
      descriptors based on the cutoffs proposed (QuBiLS-MIDAS NQ-MDs) with regard to
      the results obtained when all inter-atomic relations are considered (QuBiLS-MIDAS
      KA-MDs - 'Keep All'). A principal component analysis shows that the novel
      molecular cutoffs codify chemical information captured by the respective QuBiLS
      MIDAS KA-MDs, as well as information not captured by the latter. Lastly, a QSAR
      study to obtain deeper knowledge of the contribution of the proposed methods was
      carried out, using four molecular datasets (steroids (STER), angiotensin
      converting enzyme (ACE), thermolysin inhibitors (THER) and thrombin inhibitors
      (THR)) widely used as benchmarks in the evaluation of several methodologies. One
      to four variable QSAR models based on multiple linear regression were developed
      for each compound dataset following the original division into training and test
      sets. The results obtained reveal that the novel cutoff procedures yield superior
      performances relative to those of the QuBiLS-MIDAS KA-MDs in the prediction of
      the biological activities considered. From the results achieved, it can be
      suggested that the proposed N-tuple topological/geometric cutoffs constitute a
      relevant criteria for generating MDs codifying particular atomic relations,
      ultimately useful in enhancing the modelling capacity of the QuBiLS-MIDAS 3D-MDs.

PMID- 27707005
TI  - Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an
      in vitro study.
AB  - CONTEXT: Obesity is a major global health problem associated with various adverse
      effects. Pharmacological interventions are often necessary for the management of
      obesity. Orlistat is an FDA-approved antiobesity drug which is a potent inhibitor
      of intestinal lipases. OBJECTIVE: In the current study, orlistat was evaluated
      for its genotoxic potential in human lymphocyte cells in vitro and was compared
      with that of another antiobesity drug sibutramine, presently withdrawn from
      market due its undesirable health effects. Caffeine intake may be an additional
      burden in people using anorectic drugs, therefore, further work is needed to be
      carried out to evaluate the possible effects of caffeine on orlistat-induced DNA
      damage. MATERIALS AND METHODS: Human lymphocytes were exposed to orlistat (250,
      500 and 1000 MUg/ml), sibutramine (250, 500 and 1000 MUg/ml) and caffeine (25,
      50, 75, 100, 125 and 150 MUg/ml) to assess their genotoxicity by comet assay in
      vitro. In addition, lymphocytes were co-incubated with caffeine (50, 75 and 100
      MUg/ml) and a single concentration of orlistat (250 MUg/ml). RESULTS: Orlistat
      and sibutramine were genotoxic at all concentrations tested, sibutramine being
      more genotoxic. Caffeine was found to be genotoxic at concentrations 125 MUg/ml
      and above. Co-treatment of orlistat with non-genotoxic concentrations (50, 75 and
      100 MUg/ml) of caffeine lead to a decrease in DNA damage. DISCUSSION AND
      CONCLUSION: Orlistat can induce DNA damage in human lymphocytes in vitro and
      caffeine was found to reduce orlistat-induced genotoxicity.

PMID- 27707006
TI  - Background and episodic breathlessness in advanced cancer patients followed at
      home.
AB  - BACKGROUND: The aim of this study was to assess the phenomenon of episodic
      breathlessness in advanced cancer patients followed by palliative care services
      at home. METHODS: A consecutive sample of patients with advanced cancer, admitted
      to home care for a period of six months, was surveyed. The presence of background
      breathlessness and episodic breathlessness, their intensity, and drugs used for
      their treatment were collected. Factors inducing episodic breathlessness, and its
      influence on daily activities were investigated. RESULTS: Three hundred forty
      seven advanced cancer patients admitted to home palliative care were surveyed.
      The prevalence of breathlessness was 35.3%. The mean intensity of breathlessness
      was 3.8 (SD 1.96), out of a maximum score of 10 for worst imaginable. Sixty
      patients (49.2%) were receiving drugs for background breathlessness. In the
      multivariate analysis the risk of breathlessness increased with cardiovascular
      disease, chronic obstructive pulmonary disease, and lung cancer while it
      decreased in patients with a better performance status. The prevalence of
      episodic breathlessness in patients with background breathlessness was 79.5% and
      its mean intensity was 7.1 (SD 1.5, range 2-10). The mean duration of episodic
      breathlessness was 28.6 minutes (SD 47.1, range 1-300 minutes). Forty-three
      patients (44.3%) were receiving one or more drugs as needed. The majority of
      episodic breathlessness events were triggered by activity. Episodic
      breathlessness was interfering with daily activities in 65 patients (67%).
      Episodic breathlessness wasn't associated with any variable taken into
      consideration. CONCLUSION: This study showed that episodic breathlessness
      frequently occurs in advanced cancer patients admitted to home care, is severe in
      intensity, is triggered in most cases by activity, and is characterized by a
      short duration which requires rapid measures.

PMID- 27707007
TI  - Evaluation of antioxidant activity, total phenolics, total flavonoids and LC
      MS/MS characterisation of phenolic constituents in Stachys lavandulifolia.
AB  - The aim of this study was to evaluate phenolics profile and antioxidant activity
      of Stachys lavandulifolia. Total phenolics (TP), total flavonoids (TF), DPPH*
      assay (IC50), ferric ion reducing antioxidant power (FRAP) and total antioxidant
      capacity (TAC) of the methanolic extract were measured. The content of TP, TF,
      IC50, FRAP and TAC, were obtained as 16.59 gallic acid equiv./g dry matter (DM),
      4.48 mg quercetin equiv./g DM, 2.07 (MUg/mL), 0.014 (absorbance/mg phenolic) and
      14.61 (mg BHT equiv./g DM), respectively. The results showed that S.
      lavandulifolia, compared to other species of Stachys, had moderate TP content
      with desirable antioxidant activity. Subsequently, 59 various phenolic compounds
      were identified and confirmed in the methanolic extract of S. lavandulifolia
      using high mass accuracy by MS2 experiments. The compounds consisted of 6
      hydroxybenzoic acids and hydroxybenzoic aldehydes, 9 hydroxycinnamic acids, 1
      coumarin, 32 flavonoids, 3 lignans, 2 stilbenes, 3 tannins and 3 other phenolics.

PMID- 27707008
TI  - Social neuroscience: undoing the schism between neurology and psychiatry.
AB  - Multiple disorders once jointly conceived as "nervous diseases" became segregated
      by the distinct institutional traditions forged in neurology and psychiatry. As a
      result, each field specialized in the study and treatment of a subset of such
      conditions. Here we propose new avenues for interdisciplinary interaction through
      a triangulation of both fields with social neuroscience. To this end, we review
      evidence from five relevant domains (facial emotion recognition, empathy, theory
      of mind, moral cognition, and social context assessment), highlighting their
      common disturbances across neurological and psychiatric conditions and discussing
      their multiple pathophysiological mechanisms. Our proposal is anchored in
      multidimensional evidence, including behavioral, neurocognitive, and genetic
      findings. From a clinical perspective, this work paves the way for dimensional
      and transdiagnostic approaches, new pharmacological treatments, and educational
      innovations rooted in a combined neuropsychiatric training. Research-wise, it
      fosters new models of the social brain and a novel platform to explore the
      interplay of cognitive and social functions. Finally, we identify new challenges
      for this synergistic framework.

PMID- 27707009
TI  - An inverse problem in estimating the laser irradiance and thermal damage in laser
      irradiated biological tissue with a dual-phase-lag model.
AB  - The aim of this study is to solve an inverse heat conduction problem to estimate
      the unknown time-dependent laser irradiance and thermal damage in laser
      irradiated biological tissue from the temperature measurements taken within the
      tissue. The dual-phase-lag model is considered in the formulation of heat
      conduction equation. The inverse algorithm used in the study is based on the
      conjugate gradient method and the discrepancy principle. The effect of
      measurement errors and measurement locations on the estimation accuracy is also
      investigated. Two different examples of laser irradiance are discussed. Results
      show that the unknown laser irradiance and thermal damage can be predicted
      precisely by using the present approach for the test cases considered in this
      study.

PMID- 27707010
TI  - Novel oral anticoagulants: beyond the myth.

PMID- 27707011
TI  - A Multi-locus Approach to Characterization of Major Quantitative Trait Loci
      Influencing Hb F Regulation in Chinese beta-thalassemia Carriers.
AB  - Genetic association studies showed that Hb F is under the influence of major
      quantitative trait loci (QTL) in beta-thalassemia (beta-thal) carriers. Single
      nucleotide polymorphisms (SNPs) at three major QTLs, BCL11A, HBS1L-MYB intergenic
      region and XmnI-HBG2 were individually validated in univariate models. However,
      their relative effect sizes on Hb F regulation are unknown. We genotyped 99
      Chinese beta-thal carriers for the three major QTLs and performed genetic
      association studies using three different statistical models, including mass
      univariate analysis, multivariate linear regression and partial least square
      regression structural equation modeling (PLS-SEM). Performances of the three
      models were compared and effect sizes of the three QTLs in a multivariate model
      were assessed. Traditional mass univariate analysis and multivariate linear
      regression showed limited statistical power in our small cohort and the latter
      was constrained by multicollinearity. Partial least structural equation modeling
      showed significant positive associations of each QTL (p <0.05) with Hb F
      regulation, together explained 34.4% of variance. The HBS1L-MYB intergenic region
      polymorphism (HMIP) demonstrated the highest effect on Hb F prediction with
      effect size f2 0.294. PLS-SEM offered a statistically powerful multivariate model
      for multi-locus genetic association studies. We reproduced findings of previous
      studies with a much smaller cohort and demonstrated HMIP as the strongest
      regulator of Hb F in Chinese beta-thal carriers.

PMID- 27707012
TI  - Working memory function is linked to trauma exposure, independently of post
      traumatic stress disorder symptoms.
AB  - INTRODUCTION: The purpose of the study was to examine how working memory (WM) may
      be related to exposure to potentially traumatic events and symptoms of post
      traumatic stress disorder (PTSD). METHOD: In four studies, we measured WM
      function using adaptations of the running span and the reading span tasks. We
      compared the performance of women reporting experiences of sexual abuse to
      control participants (total n = 144 controls and 84 victims). We measured
      severity of the sexual abuse experiences as well as exposure to general life
      stress. RESULTS: In all studies, trauma-exposed participants showed significantly
      lower WM function compared to control participants. In addition to traditional
      null hypothesis testing, we used a mini-meta analysis to estimate the combined
      estimated effect size of this difference, which was in the moderate range (d =
      0.43 with 0.15-0.70 95% confidence interval). Regression equations showed that
      PTSD symptoms did not mediate the relationship between trauma exposure and WM
      function. CONCLUSIONS: Our results show that trauma exposure per se can be
      associated with important cognitive correlates even in individuals who do not
      develop psychopathological reactions.

PMID- 27707014
TI  - Conferences.

PMID- 27707013
TI  - RCN Scotland seeks right stuff.
AB  - Ensuring that nurses receive the 'right leadership' is one of the five measures
      called for in a new RCN Scotland campaign, entitled Right for Nurses, Right for
      Patients.

PMID- 27707015
TI  - Vantage point.
AB  - OUR HEAD of nutrition recently presented a 'protected meal-times initiative' at a
      ward sisters' meeting. This is designed to ensure patients are undisturbed and
      that wards are quiet during mealtimes. The ensuing discussion revealed
      significant disagreement as to whether visitors were helpful, or a nuisance (
      Baker 2003 ).

PMID- 27707016
TI  - Uk nursing director joins Iraqi authority.
AB  - Former director of nursing Jane Wilshaw left the UK last month as part of a four
      strong team to advise on developing healthcare services in Iraq.

PMID- 27707018
TI  - British nursing at your convenience.
AB  - Convenience is at the heart of many of our activities nowadays, and if itis
      important to you, go to www.british-nursing.com/ and enter an Aladdin's cave of
      links to agencies and information on, for example, current charges for agency
      staff around the UK.

PMID- 27707019
TI  - Eureka!
AB  - Eureka! is the description of each of a series of web based solutions to clinical
      governance problems that appear on the NHS Modernisation Agency's clinical
      governance support team's website. According to the site's blurb: 'Developing a
      practical approach to clinical governance is a complex business. Experience has
      shown that determination can overcome these barriers to progress, and give teams
      a sense of Eureka!' - not strictly a noun of course but clearly being used as one
      here.

PMID- 27707020
TI  - ?
AB  - SPRING IS HERE, the primroses are out and expectations are high. Over the next
      year we will be implementing the biggest revolution in NHS pay with the
      introduction of the consultant and general medical services contracts, the
      European working time directive and Agenda for Change. As well as affecting pay,
      this revolution is expected to bring about service and career modernisation, role
      development and a new workforce profile.

PMID- 27707022
TI  - Ready for inspection.
AB  - This month sees the launch of the new Commission for Healthcare Audit and
      Inspection (CHAI) website. It offers new visitors an introduction to the work of
      the organisation but also carries news, details of CHAI vacancies and information
      about consultations. Its launch coincides with that of the new organisation
      itself. Access www.chai.org.uk/ for more information.

PMID- 27707021
TI  - Consultations for better standards.
AB  - The web is an excellent vehicle for carrying information relating to
      consultations. Last month saw the launch of the health department's block busting
      Standards for Better Health: Health care standards for services under the NHS.
      Access www.dh.gov.uk/consultations/liveconsultations/fs/en and you willfind
      everything you need to know tobecome involved in shaping thenext stage of NHS
      improvements.

PMID- 27707023
TI  - Independent sector urged to adopt agenda for change.
AB  - Independent sector employers are being encouraged by the RCN to adopt the Agenda
      for Change pay and grading system.

PMID- 27707024
TI  - Mother of all websites.
AB  - Arguably the 'mother of all websites', at least for those of us working in the
      NHS in England, has had a revamp, writes Steven Black. The Department of Health
      recently launched an updated site that is designed to be clearer and easier to
      navigate than before.

PMID- 27707025
TI  - ?
AB  - Nursing directors, modern matrons and ward managers are being targeted this month
      as part of a campaign to ensure that patients have 'protected mealtimes'. The UK
      wide campaign was launched last month with the support of the RCN and NHS Estates
      by the Hospital Caterers Association (HCA). Association patron Loyd Grossman is
      due to give an update on the government's 'better hospital food' programme at the
      51st HCA annual conference later this month. For details, access
      www.hospitalcaterers.org See also page 8.

PMID- 27707026
TI  - Nurse directors join BME advisory group.
AB  - Senior nurses have responded to calls by the English chief nursing officer (CNO)
      to join her advisory group on black and minority ethnic (BME) issues.

PMID- 27707028
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27707027
TI  - Fresh delay over release of senior nurse pay details.
AB  - The RCN has expressed concern over the government's further postponement of
      announcing details of how senior nurse pay will be calculated.

PMID- 27707029
TI  - Levelling the playing fieldAngela Watts and Simon Green discuss the harmonisation
      and standardisation of employment terms and conditions under Agenda for Change.
AB  - ONE OF the principal changes brought about by introducing Agenda for Change (AfC)
      is the harmonisation and standardisation of NHS staff employment terms and
      conditions, such as the amount of annual leave, contracted hours and unsocial
      hours payments.

PMID- 27707030
TI  - Need for change.
AB  - THE CASE of R v Bournewood ( 1998 ) highlights the flaws in current legislation
      and emphasises the need for change. In this case, a 43-year-old man with autism
      who clearly lacked capacity was detained as a voluntary patient under the Mental
      Health Act 1983.

PMID- 27707031
TI  - Nurse nurse.

PMID- 27707032
TI  - Promoting good practice.
AB  - Meanwhile, the Scottish Executive's Centre for Change and Innovation, which was
      set up to identify and promote good practice and increase the pace of change to
      benefit patients, has an informative website at www.cci.scot.nhs.uk which
      provides details of a range of innovative projects currently underway. The site
      has main sections focusing on, among other things, national and local programmes,
      best practice examples, feedback, advice on managing teams, and developing
      organisations. It also provides a link to the NHS Education for Scotland
      electronic library.

PMID- 27707034
TI  - Making a difference.
AB  - THE INQUIRY INTO children's heart surgery at Bristol Royal Infirmary between 1984
      1995 has already had a profound impact on the NHS. It was evidence given to the
      Inquiry which led to the uncovering of the extent of organ retention, without
      consent, which has involved many of you in additional activities in your own
      trust.

PMID- 27707035
TI  - Websites.

PMID- 27707033
TI  - Efficiency of radiation-induced base lesion excision and the order of enzymatic
      treatment.
AB  - PURPOSE: To clarify whether initial base excision repair processes at clustered
      DNA damage sites comprising multiple base lesions affect subsequent excision
      processes via the formation of additional strand breaks by glycosylase and
      apurinic/apyrimidinic (AP) endonuclease base excision enzymes. MATERIALS AND
      METHODS: Plasmid DNA (pUC18) as a model DNA molecule was exposed to high-linear
      energy-transfer (LET) ionizing radiation (He2+ or C6+ ions) or low-LET ionizing
      radiation (X-rays) under various conditions to produce varied radical-scavenging
      effects. pUC18 was then treated sequentially or simultaneously with two bacterial
      base excision enzymes (glycosylases), namely, endonuclease III and
      formamidopyrimidine-DNA glycosylase, which convert pyrimidine (or abasic [AP]
      site) and purine (or AP site) lesions to single-strand breaks (SSB),
      respectively. Yields of additional SSB or double-strand breaks (DSB) as digestion
      products were examined after changing the order of enzymatic treatment. RESULTS:
      There were few differences among the enzymatic treatments, indicating that
      treatment order did not affect the final yields of additional SSB or DSB formed
      by glycosylase activity. This suggests that of the total damage, the fraction of
      clustered damage sites with a persistent base lesion dependent on the order of
      glycosylase treatment was insignificant if present. CONCLUSION: Base lesion
      clusters induced by high- or low-LET radiation appear three or more base pairs
      apart, and are promptly converted to a DSB by glycosylase, regardless of the
      order of enzymatic treatment.

PMID- 27707037
TI  - Nurturing nursing leadership how does your garden grow? es your garden grow?
AB  - The 'quick fix' has become well established in popular culture, particularly on
      television, in the last few years. Take gardens for example. Nowadays, instead of
      taking time to plan and nurture a garden to renovate it, the trend is to get a
      team of experts in to transform the garden in a couple of days. The new garden
      may look impressive, but its overall sustainability and relevance to the
      environment may be questionable. Certainly, when the glare of the television
      lights and consultant horticulturist have long since gone, the impetus to
      cultivate often dissipates and year-round attention to growth lost.

PMID- 27707041
TI  - Stories abound that the budget will be handed out in one lump sum on April 1. In
      which case stand back and wait for the fireworks as the money (at least
      notionally) runs out around November 2002!
AB  - It is perhaps very timely that we are running a series on budgeting. Never has
      the basis for budgeting been more complex. It is to be hoped that at a clinical
      level, little difference will be felt. However, if you are concerned about
      strategic planning of budgets, the next two years are going to be challenging, in
      England at least.

PMID- 27707040
TI  - Code fails to protect nurses in independent sector.
AB  - A new code of practice for international recruitment of nurses and midwives has
      been criticised because it ignores exploitation in the independent sector. The
      Code of Practice for International Recruitment which was published last month,
      updates guidance from two years ago. But, according to the RCN and Unison, it
      targets only the NHS.

PMID- 27707042
TI  - UKCC guidelines aim to improve supervision of midwives.
AB  - New guidelines on supervising midwives have been published by the UKCC. The areas
      covered in the guidance include variations in practice not justified by women's
      needs or preferences, poor management of emergency care, promoting informed
      choice for women, the effectiveness of communication with women and other
      professional colleagues, and support for midwives to identify training needs and
      professional development. The midwifery committee had been concerned that despite
      the publication of other recommendations, there has been 'no apparent
      improvement' in practice.

PMID- 27707043
TI  - RCN call to 'value nurses' in Scotland.
AB  - Nurses and midwives in Scotland are pressing the Scottish Executive to fund in
      full return to practice courses. The calls have come in support of an RCN
      Scotland campaign 'Value Nurses'.

PMID- 27707044
TI  - Money follows the stars.
AB  - NHS trusts have been graded against new, hotel-style star ratings in another
      effort to improve standards. The ratings cover areas such as waiting lists and
      times, hospital cleanliness and financial performance. Chief executives of badly
      performing trusts may lose their jobs unless improvements are not made within set
      timescales. The best performing trusts will be given more control over spending,
      undergo fewer inspections and have the opportunity directly to advise the
      government on NHS policy.

PMID- 27707045
TI  - Promoting health working with young offenders.
AB  - IN 1996 the Audit Commission reported on its comprehensive survey of the youth
      justice system ( Ashford and Chard 2000 ). In the report the Commission
      identified a lack of co-ordination among the various agencies involved in the
      system, which results in inefficient working practices and enormous delays (
      Audit commission 1996 )Subsequently, the government published a White Paper (
      Home Office 1997 ) setting out the main aims of a programme of reform for the
      system, to.

PMID- 27707047
TI  - Nurse, nurse.

PMID- 27707046
TI  - Conferences.

PMID- 27707049
TI  - Understanding budgets in the NHS - part 2 putting together a budget.

PMID- 27707050
TI  - Managing copd Establishing aneffective link.
AB  - ACCORDING TO Egger et al ( 2000 ), chron-ic obstructive pulmonary disease (COPD)
      is on the increase in the UK. Associated with this increase are increases in
      mortality rates, especially in women ( Egger et al 2000 ). The condition is also
      probably grossly underdiag-nosed, and Lydick et al ( 2000 ) suggested a
      prevalence of three million people with COPD in the UK.

PMID- 27707052
TI  - Conferences.

PMID- 27707053
TI  - Reducing patient falls.
AB  - For anyone working with older people, falls and how to prevent them are major
      concerns. Two websites currently in operation offer a range of information on the
      topic. The Foundation of Nursing Studies (FoNS) has its Reducing Patient Falls
      website a www.fons.org/projects/falls/ , which allows nurses and other health
      professionals to share information about initiatives to prevent falls. The
      resources section offers downloadable tools for risk assessment, a protocol on
      using hip protectors and electronic versions of the FoNS Reducing Patient Fall
      report.

PMID- 27707051
TI  - Factors influencing the fabrication of albumin-bound drug nanoparticles (ABDns):
      part I. Albumin-bound betulinic acid nanoparticles (ABBns).
AB  - Though there are many albumin-based drug delivery systems (ABDDS) in the market,
      it is not known whether ABDDS can be applied across all chemical classes. In this
      study, we applied ABDDS to a poorly water-soluble drug betulinic acid (BA) to
      improve its aqueous solubility. Monomeric albumin-bound BA (ABBns) nanoparticles
      can be fabricated in the range of 10-20 nm. BA self-assembled with HSA at 0.1:1
      to 2:1 molar ratio within 0.5 h in phosphate buffer pH 7.4 and 8.4.
      Approximately, 85-90% BA could be loaded onto HSA in the presence of Tween 20
      (T20) and sodium cholate (NaC). The release of BA from ABBns was linear over 5
      days. In conclusion, for poorly water-soluble acidic drugs, a suitable
      solubiliser can release the drug from HSA binding site, depending on the
      aggregation number and affinity of the solubiliser for the HSA binding site.

PMID- 27707054
TI  - ?
AB  - AS ANY senior nurse manager in psychiatry will testify, our role has extended
      beyond the traditional job description. We must be able to think and plan around
      aspects of building design, service reconfiguration and new service
      commissioning.

PMID- 27707055
TI  - ?
AB  - Jean Faugier (pictured above) has resigned her position as co-directors of the
      Europian Nursing Leadership Foundation (ENLF). Professor Faugier, who was
      director of the NHS national nursing leadership project until earlier this year,
      will be pursuing other professional and personal with her grandchildren. Ali
      Handscomb and David Dawes will continue as ENLF co-directors interests, including
      working on psychodynamic aspects of leadership and spending more time with her
      grandchildren. Ali Handscomb and David Dawes will continue as ENLF co-directors.

PMID- 27707056
TI  - Exchange rates.
AB  - IN MAY this year, I was lucky enough to go to Larissa in northern Greece as part
      of Hope Exchange 2003, an annual study tour organised by the European Union's
      hospital committee and administered by the Institute of Healthcare Management
      (IHM).

PMID- 27707057
TI  - Dr Kelly's death and the subsequent political tailspin has blotted out almost
      every other conceivable element of public debate. What is happening to the summer
      discussion about health?
AB  - The dog days of August are usually given over to debates about global warming,
      the inadequacy of the UK transport system or water shortages. This year is
      different. Lord Hutton's inquiry into the death of weapons expert David Kelly has
      put a stop to all the silliness of that month and, one suspects, September and
      October as well.

PMID- 27707058
TI  - Standards aim to curb over-reliance on agency staff.
AB  - Nurse directors are being consulted over the introduction of staffing standards
      in Scotland in a move to cut agency costs.

PMID- 27707059
TI  - Nursing agencies.
AB  - The Nurses Agencies Association (NAA) was formed recently to represent all
      licensed nursing agencies in the UK. To bolster its profile, the association has
      launched its own website, www.the-naa.co.uk.

PMID- 27707060
TI  - Web links.
AB  - Websites offering links to other websites are proliferating. The US-based Emory
      University library, www.medweb.emory.edu/MedWeb/ , offers a well-established
      range of medical and health internet resources.

PMID- 27707062
TI  - On the move round up.
AB  - Promotions/new appointments.

PMID- 27707061
TI  - Vantage point.
AB  - IT SOUNDS a bit like Monty Python's 'dead parrot' sketch. From December,
      community health councils (CHCs) will be defunct, they will be ex-CHCs, they will
      be gone to meet their maker.

PMID- 27707063
TI  - On the front line.
AB  - STAFF ARE our most valuable asset. But do we have the information, skills,
      processes and culture to make the most of it? What is clear is that there is no
      single 'big bang' approach to the challenge of turning rhetoric into reality but
      rather a series of steps that lead to a coherent strategy with demonstrable
      results.

PMID- 27707064
TI  - Award-winning nurses announced.
AB  - Senior nurses representing the voluntary and independent sectors are joint
      winners of this year's Nursing Standard nursing leadership award.

PMID- 27707065
TI  - Clinical leadership programme given go-ahead.
AB  - The NHS has commissioned the RCN to run a new leadership programme for 100 multi
      professional clinical teams at English NHS trusts.

PMID- 27707066
TI  - Concern over lost foundation bids.
AB  - Senior nurses have voiced concern and disappointment after their trusts were
      excluded from the foundation trust initiative.

PMID- 27707067
TI  - Correspondence Nursing Management readers have their say.
AB  - Dear Editor, In reference to the article by Maureen Eby published in the June
      issue of NM(10,3,32-35), entitled 'Data Protection: Part One', given that
      healthcare professionals may reasonably be expected to rely on the content of the
      article, I feel that I must point out some inaccuracies.

PMID- 27707068
TI  - Senior pay proposals out for consultation.
AB  - Nurse managers have until the end of this month to give their views on Department
      of Health proposals for modernising their pay and contractual arrangements.

PMID- 27707069
TI  - Nurse to lead NHS franchise scheme.
AB  - Nurse manager Anne Heast takes over this month as chief executive of Good Hope
      Hospital NHS Trust as part of the first private sector franchise of an NHS
      hospital.

PMID- 27707070
TI  - International perspective.
AB  - An international perspective on healthcare news can be found at the newly
      launched website of US-based MedAbiliti. The site offers a collection of
      categorised medical news stories that are updated continually. Access is free and
      available either through the website, health.innovationdaily.com , or via a daily
      newsletter.

PMID- 27707072
TI  - Personal development.
AB  - A listing of courses offering personal development in leadership has been
      compiled and posted on the North East London Workforce Development Confederation
      website, writes Steven Black.

PMID- 27707071
TI  - Public and patient involvement.
AB  - Public and patient involvement in the NHS is one of the new Department of Health
      mantras, and one source of useful information you can pass on to service users is
      the Consumers in NHS Research website at www.conres.co.uk/dat.htm.

PMID- 27707074
TI  - Nurse.

PMID- 27707073
TI  - Government information.
AB  - If UK government information is what you are after, you could do worse than go to
      www.tagish.co.uk/tagish/Links/ , where you will find a comprehensive listing of
      local and national government links. The UK healthcare providers listing is as
      good a collection of links for health services as anyone needs as a starting
      point for gaining information on UK trusts or hospitals.

PMID- 27707075
TI  - Investing in the future a cross-organisational approach.
AB  - THE NHS CANCER PLAN ( Department of Health 2000a ) identifies the need to develop
      staff in order to deliver the highest quality cancer care and meet the complex
      needs of patients with cancer. Nurses make up the single largest professional
      group in this workforce.

PMID- 27707076
TI  - Data protection: part one.
AB  - DATA IN manual systems have to be changed under certain circumstances, and in
      certain ways, to retain documented records of who made what changes, why and
      when.

PMID- 27707077
TI  - Scotland's rainbow parliament.
AB  - THE PEOPLE HAVE SPOKEN and the result is not quite what the press and
      commentators were expecting. Both Scottish Labour and the Scottish National Party
      (SNP) lost out to the smaller parties and independents with the Green Party and
      the Scottish Socialist Party making major gains ( Table 1 ).

PMID- 27707078
TI  - Development and effect of storage on the stability of enriched flavonoid fraction
      of Cecropia glaziovii-loaded PLGA nanoparticles.
AB  - Studies employing Cecropia glaziovii Snethl leaves have shown great potential in
      regard to their antiviral activity, mainly related to the phenolic compounds
      present in this species. The main goal of this work is to combine the therapeutic
      potential of this species with new technological strategies targeted at the
      development of an herbal nanoparticulate system for the preparation of a
      phytotherapeutic formulation. Poly (lactic-co-glycolic acid) nanoparticles
      containing the enriched flavonoid fraction of Cecropia glaziovii Snethl were
      developed through a study for the choice of preparation technique, amount of drug
      and surfactants used. These nanostructured systems were characterized by particle
      size, polydispersity, zeta potential, encapsulation efficiency and drug-loading
      capacity. A stability study of the formulations was conducted at room temperature
      over a period of 60 days. The optimal formulation that best fit the
      characteristics of the encapsulated material was determined. Sorbitan monooleate
      and the poloxamer 188 resulted in better colloidal stability, added to the
      organic and aqueous phases, respectively. These findings suggest that in the
      field of nanoparticles stability, it is important to evaluate the composition of
      the nanoparticulate system. This work highlights the importance of the
      optimization process, searching for a good formulation with suitable structural
      stabilization.

PMID- 27707079
TI  - The protective effect of cilostazol on transverse rectus abdominis myocutaneous
      flap in rats.
AB  - OBJECTIVE: Transverse Rectus Abdominis Myocutaneous (TRAM) flap is commonly used
      in breast reconstruction. The aim of this study is to demonstrate the effects of
      cilostazol on TRAM flap viability in a rat TRAM model. METHODS: Twenty-four
      Wistar rats were used. They were divided into four groups. Rats in Group 1 were
      applied TRAM flap. In Group 2, cilostazol 30 mg/kg was administered to rats via
      oral gavage 3 hours before the flap surgery. After the flap surgery, cilostazol
      30 mg/kg was administered via oral gavage twice a day for 7 days. In Group 3
      before the flap surgery, cilostazol 30 mg/kg was administered via oral gavage
      twice a day for 7 days, and treatment continued for 7 more days after the flap
      surgery. In Group 4 before the flap surgery, cilostazol 30 mg/kg was administered
      via oral gavage twice a day for 7 days and treatment was discontinued after the
      flap surgery. RESULT: The mean necrosis rate in Group 1 was 41.69%, in Group 2 it
      was 27.0%, in Group 3 it was 6.66%, and in Group 4 it was 11.2%. The necrosis
      rate in Group 1 was found to be statistically significantly higher than other
      groups (p < .01), the necrosis rate in Group 2 was found to be statistically
      significant higher than Groups 3 and 4 (p < .01), and the necrosis rate in Group
      4 was found to be statistically significant higher than Group 3 (p < .01).
      CONCLUSION: Cilostazol treatment seemed to increase the viability of TRAM flap,
      especially when administered as adjuvant therapy.

PMID- 27707080
TI  - National service framework a GNP response.
AB  - The National Service Framework (NSF) for older people is a comprehensive strategy
      which seeks to ensure fair, high quality, integrated health and social care
      services for older people. It sets out a ten-year programme of action to address
      specific challenges, and the RCN Gerontological Nursing Programme has now planned
      what action the team intends to take towards achieving each of the standards,
      including the following.

PMID- 27707081
TI  - Nursing or personal care - who decides?
AB  - The consultation period for the government's draft guidance to implement NHS
      funded nursing in nursing homes in England has ended, but the controversy and
      problems surrounding it are likely to continue for some time.

PMID- 27707082
TI  - Activities of daily living and transition to community living for adults with
      intellectual disabilities.
AB  - BACKGROUND: As adults with intellectual disability (ID) in Ireland move to the
      community from residential settings, the changed environment is intended to
      increase opportunities for occupational engagement, autonomy and social
      relationships. It is important to consider how increased resources and
      opportunities available within the community can be optimized to promote
      engagement and quality of life. AIMS: This paper investigates if and how ADL and
      IADL performance of people ageing with ID is related to place of residence.
      METHODS: ADL and IADL performance of adults with ID in Ireland across different
      living situations was analyzed using descriptive and bivariate analysis of data
      collected from the Intellectual Disability Supplement to the Irish Longitudinal
      Study on Ageing (IDS TILDA). RESULTS: Greater ability to perform ADL and IADL was
      noted in those living in independent or community group home settings when
      compared to traditional residential settings. Place of residence was strongly
      related to ADL and IADL performance. CONCLUSION AND SIGNIFICANCE: Given that
      people with ID will likely require physical and social supports to complete ADL
      and IADL when transitioning to community living from residential settings, an
      occupational justice perspective can inform occupational therapists working with
      people with ID, facilitating successful transitions to community living.

PMID- 27707083
TI  - Potentiality of syringetin for preferential radiosensitization to cancer cells.
AB  - PURPOSE: To examine the enhancing effects of syringetin on the radiosensitivity
      of normal and cancer cells, and the related mechanism. MATERIALS AND METHODS: We
      used normal human lung and mouse fibroblasts as well as human lung and mouse
      cancer cells derived from the above normal fibroblasts. Cell radiosensitivity was
      measured using a colony formation assay. Apoptosis was analyzed with DAPI
      staining and Western blots. DNA lesions were analyzed with gammaH2AX
      immunofluorescent staining. RESULTS: The colony formation assay showed that
      syringetin enhanced radiosensitivity more effectively in cancer cells (H1299 and
      C3H/MCA clone 15) compared with normal cells (HFL-III and C3H/10T1/2). The
      radiosensitizing effect of syringetin was observed in mutated p53 and wild-type
      p53-transfected H1299 cells regardless of p53 status. Apoptosis was more
      frequently observed in X-ray-irradiated H1299 cells combined with syringetin
      compared with X-ray-only-treated cells. Enhanced apoptosis by syringetin was not
      observed in HFL-III cells. Western blot analysis showed that X-ray-induced
      Caspase-3 activation was enhanced by syringetin in H1299 cells. The number of X
      ray-induced DNA double-strand breaks (DSB) measured by quantitative analysis of
      gammaH2AX foci was the same for H1299 cells treated with X-rays with or without
      syringetin. CONCLUSIONS: This study supports the hypothesis that syringetin
      enhances radiosensitivity more effectively in cancer cells than in normal cells
      through enhancement of the Caspase-3-mediated apoptosis pathway. Syringetin could
      be useful in the development of novel efficacious radiosensitizers.

PMID- 27707086
TI  - A betrayal of trust?
AB  - Nearly five years after the report of the Royal Commission on Long Term Care (
      1999 ), a statement by nine members of the Commission ( 2003 ) has accused the
      government of 'betraying' older people.

PMID- 27707084
TI  - Generalized Seizures after Experimental Traumatic Brain Injury Occur at the
      Transition from Slow-Wave to Rapid Eye Movement Sleep.
AB  - Sleep disturbances commonly occur after traumatic brain injury (TBI) and may
      predispose patients to epileptic seizures. We hypothesized that unprovoked
      seizure occurrence post-TBI depends on the sleep-wake cycle, and that the
      electrographic characteristics of a given sleep stage provide biomarkers for post
      traumatic epilepsy (PTE). We show, in a rat lateral fluid percussion model, that
      92% of spontaneous generalized seizures occur during the transition from stage
      III to rapid eye movement sleep. Moreover, a reduction in spindle duration and
      dominant frequency during the transition stage present as specific and sensitive
      noninvasive biomarkers for experimentally induced PTE with generalized
      electrographic seizures.

PMID- 27707087
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27707089
TI  - ?
AB  - Garden birds are benefiting from a new Heritage Lottery-funded project that
      combines meals on wheels for older people with food for their feathered friends.
      Age Concern's meals on wheels team in Acomb, near Hexham, has teamed up with the
      Royal Society for the Protection of Birds to deliver feasts for both clients and
      birds. The memories that older people have about changes to bird populations and
      the countryside are to be recorded as part of the project, which, Age Concern
      says, has already had a positive impact - on both people and birds.

PMID- 27707090
TI  - Using SPSS syntax: a beginner's guide Jacqueline Collier Using SPSS syntax: a
      beginner's guide Sage Pages: 216 L24.99 9781412922180 1412922186 [Formula: see
      text].
AB  - As someone who is comfortable with analysing data in SAS using coding language,
      it is perplexing that I run from the use of syntax in SPSS. But, my apprehension
      has subsided with the Collier's guide. Syntax command can automate processes,
      increase reproducibility and give the user broader access to features otherwise
      unavailable in SPSS.

PMID- 27707091
TI  - Doing qualitative research David Silverman Doing qualitative research Sage Pages:
      472 L27.99 9781848600331 184860033X [Formula: see text].
AB  - Professor Silverman's reputation in the world of qualitative research precedes
      him and I am mindful of his status as I write this review. I am similarly mindful
      of Denzin's equally eminent standing and note his positive review on the cover of
      this book in which he describes the content as 'exceedingly thoughtful, practical
      and comprehensive ....'

PMID- 27707092
TI  - Key topics in surgical research and methodology Thanos Athanasiou Key topics in
      surgical research and methodology , Haile Debas and Ara Darzi Springer Pages:
      1090 L180 9783540719144 3540719148 [Formula: see text].
AB  - If the editors' intention was to produce a comprehensive text book that will be
      of value to healthcare professionals interested in surgical research and
      improvements in health care, they have succeeded.

PMID- 27707094
TI  - Have a nice day.
AB  - Today's NHS is dynamic, multifaceted and complex, and the task of delivering care
      is not easy. Receiving care is a profoundly personal experience and perceptions
      of the quality of care being offered are highly individual. As part of their
      endeavours to measure the quality of service being offered at Maesteg Community
      Hospital, South Wales, the staff of the day hospital wanted to obtain the views
      of the older people who attended. Twenty-one were selected to reflect 'typical'
      users of the day hospital services, including both past and present users and
      those who attended on different days. They ranged in age from 65 to 80-plus, with
      various abilities and care needs.

PMID- 27707095
TI  - An inspector calls.
AB  - In April this year the National Care Standards Commission (NCSC) became
      responsible for the registration and inspection of all care homes and private
      healthcare facilities in England. And I have just struggled through the
      Manchester traffic in the pouring rain after visiting the NCSC to have my
      passport, driving licence and address checked for the Criminal Records Bureau.
      This is so that I can register as a care home manager - a job I have done for the
      last 12 years, and I've been registered for seven of those years! I haven't yet
      been asked to sit an exam, as many other managers have apparently been asked to
      do, but nothing would surprise me.

PMID- 27707096
TI  - ?
AB  - This study focused on the nutrition-related care needs of 40 residents of nursing
      homes in the Stockholm area. Interviews conducted with the registered nurses
      responsible for their care were used to provide the required information.

PMID- 27707097
TI  - Assessing for delirium.
AB  - Delirium is a complex phenomenon that can develop at any time in life. It is most
      likely to occur in older age and in those people who already have cognitive
      impairment such as dementia ( Levkoff et al 1988 , American Psychiatric
      Association 1999 ).

PMID- 27707098
TI  - Acute concerns.
AB  - In July the House of Commons health committee published the findings of its
      investigation into delayed hospital discharges. In the second quarter of 2001
      2002, there were 7,065 delayed discharges of patients of all ages, which
      accounted for 6 percent of all acute beds. Although it is difficult to calculate
      precise figures, it seems that the cost of such delays may be in the region of
      L720 million per year. In response, the committee proposed a range of potential
      solutions, including.

PMID- 27707101
TI  - Hooked on linking research to real life.
AB  - PROFESSOR CHRISTINE Norton is best known for her research into faecal
      incontinence and her ability to combine clinical and academic roles successfully.

PMID- 27707099
TI  - Medication adherence as a learning process: insights from cognitive psychology.
AB  - Non-adherence to medications is one of the largest contributors to sub-optimal
      health outcomes. Many theories of adherence include a 'value-expectancy'
      component in which a patient decides to take a medication partly based on
      expectations about whether it is effective, necessary, and tolerable. We propose
      reconceptualising this common theme as a kind of 'causal learning' - the patient
      learns whether a medication is effective, necessary, and tolerable, from
      experience with the medication. We apply cognitive psychology theories of how
      people learn cause-effect relations to elaborate this causal-learning challenge.
      First, expectations and impressions about a medication and beliefs about how a
      medication works, such as delay of onset, can shape a patient's perceived
      experience with the medication. Second, beliefs about medications propagate both
      'top-down' and 'bottom-up', from experiences with specific medications to general
      beliefs about medications and vice versa. Third, non-adherence can interfere with
      learning about a medication, because beliefs, adherence, and experience with a
      medication are connected in a cyclic learning problem. We propose that by
      conceptualising non-adherence as a causal-learning process, clinicians can more
      effectively address a patient's misconceptions and biases, helping the patient
      develop more accurate impressions of the medication.

PMID- 27707102
TI  - Interpreting statistical findings: a guide for health professionals and students
      Jan Walker Interpreting statistical findings: a guide for health professionals
      and students and Palo Almond L21.99 232pp 9780335235971 80199206773 - 0199206775
      [Formula: see text].
AB  - THIS BOOK contains a lot of information in a slim volume. on the one hand this is
      a bonus because it allows readers to focus on the main issues quickly. The
      downside is a rather brisk style of writing which crams a lot of information into
      a small space.

PMID- 27707103
TI  - Introducing research and evidence-based practice for nurses Jeremy Jolley
      Introducing research and evidence-based practice for nurses Pearson Education
      L19.99 168 9780273719168 0273719165 [Formula: see text].
AB  - EVIDENCE BASED practice is an increasingly hot topic and this book is timely
      because of both the move towards an all-graduate profession and the increase in
      the use of evidence in nursing. Nurses need to understand the relationship
      between research, evidence and practice and then to be able to use that
      understanding to provide the best possible care for the patient.

PMID- 27707104
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27707106
TI  - Inspiring us to inspire others.
AB  - All nurses who genuinely care about older people will have encountered difficult
      situations that necessitate understanding, help and support. At times like this,
      good leaders can be crucial. They can make the difference between us mustering
      resources to overcome the challenges, and being overwhelmed by them.

PMID- 27707105
TI  - Interviews in qualitative research Nigel King Interviews in qualitative research
      and Christine Horrocks SAGE Publishing L21.99 248pp 9781412912570 1412912571
      [Formula: see text].
AB  - Planning a qualitative research project takes more than just the identification
      of a research question. it requires the researcher to explore and explain how
      they view the world, and to determine in what context their research question
      exists before they can even begin to design their project.

PMID- 27707107
TI  - ?
AB  - Attention is increasingly being paid to the issue of violence and aggression
      against clinical staff. This study carried out in England employed an anonymous
      semistructured questionnaire sent to all nursing, therapy and psychology staff in
      a unit providing services for older people and people who had suffered a head
      injury. The definition of violence was an open one, asking respondents about
      incidents 'in which violence or aggression was a feature and in which you were a
      victim'. The response rate to the questionnaire was 34 per cent. Fiftyone per
      cent of the staff had experienced an incident of violence or aggression in the
      previous year. Two respondents reported patient violence or aggression which they
      felt had been provoked by staff. Of those who reported consequences from the
      incident, psychological effects were the most common. Even though the trust in
      which the study was carried out had a staff support department, two thirds of the
      sample said they were unaware of its existence. The authors conclude by
      suggesting that a national survey of staff support initiatives may be worthwhile.

PMID- 27707108
TI  - Hip protectors and complianceFollowing our feature on hip protectors in the may
      issue of Nursing Older People, sue witchard considers compliance - from a project
      nurse's experience and perspective.
AB  - As a project nurse for hip protection on wards for older people at King's College
      Hospital, London, I gained unique insights into a number of issues surrounding
      compliance with hip protectors. I had two main questions regarding compliance.

PMID- 27707109
TI  - Efficacy of Particulate Amniotic Membrane and Umbilical Cord Tissues in
      Attenuating Cartilage Destruction in an Osteoarthritis Model.
AB  - Osteoarthritis (OA) is a progressive degenerative joint disease, and to date, no
      disease-modifying OA drug exists. Amniotic membrane and umbilical cord products
      have been used clinically in several diseases due to their anti-inflammatory and
      antiscarring properties. In the present study, we sought to evaluate whether a
      particulate amniotic membrane and umbilical cord (AM/UC) matrix could aid in
      attenuating disease progression. Lewis rats underwent medial meniscus transection
      (MMT) to induce OA. Two weeks after surgery, animals received intra-articular
      injections (50 MUL) of either 50 or 100 MUg/MUL particulate AM/UC or saline
      control and were subsequently euthanized 1 or 4 weeks later. Cartilage
      degeneration was assessed using both histological scoring methods and equilibrium
      partitioning of an ionic contrast agent-microcomputed tomography (EPIC-MUCT).
      EPIC-MUCT analysis demonstrated that overall cartilage destruction was
      attenuated, with a significant increase in both cartilage thickness and volume as
      well as a significant decrease in total lesion area in animals injected with
      either dose of particulate AM/UC at 1 week, but only a high dose at 4 weeks
      postinjection. Osteoarthritis Research Society International (OARSI) histology
      scores of tibial sections corroborated EPIC-MUCT results. Overall joint
      destruction was attenuated in animals injected with either dose of AM/UC tissue
      compared with saline-injected control animals at 1 week postinjection. Only high
      dose AM/UC-injected animals continued to show less overall joint destruction by 4
      weeks postinjection. Intra-articular injection of particulate AM/UC tissue
      attenuates cartilage degradation in a rat MMT model of OA, suggesting that it may
      be able to slow joint destruction in patients with OA.

PMID- 27707111
TI  - Commentary on Fallon and Horwath.

PMID- 27707110
TI  - Designing New Psychosocial Treatments for Schizophrenia.

PMID- 27707112
TI  - Commentary on Liberman and Corrigan.

PMID- 27707114
TI  - Commentary on Yeomans, Selzer, and Clarkin.

PMID- 27707113
TI  - Response to Soloff.

PMID- 27707115
TI  - Designing New Psychosocial Treatments for Serious Psychiatric Disorders.

PMID- 27707122
TI  - Commentary on Corin and Lauzon.

PMID- 27707123
TI  - Commentary on Garety.

PMID- 27707125
TI  - Intensive Clinical Studies.

PMID- 27707124
TI  - Relationships with Patients in Oncology: Can a Clinician Be a Friend?

PMID- 27707147
TI  - An evaluation of a frontline led quality improvement initiative.
AB  - Purpose The Edmonton Zone, one of five Zones in Alberta Health Services (the
      health system in the province of Alberta, Canada), established a quality
      management framework (QMF) as a means to improve the delivery of high quality
      health care in the spring of 2014. The purpose of this research study was to
      understand the factors that facilitated or hindered the implementation of a
      quality improvement (QI) initiative for hand hygiene led by a newly formed
      frontline unit quality council (UQC), a part of the QMF, based out of the
      pediatric intensive care unit (PICU) at the Stollery Children's Hospital in the
      Edmonton Zone. This research will provide an understanding of the newly
      established QMF in the Edmonton Zone and the factors needed to foster the ongoing
      development of frontline UQC that do improvement work as part of their daily
      routine. Design/methodology/approach Using a qualitative case study research
      design data were collected using semi-structured open-ended interviews with six
      key stakeholders (one registered nurse, one physician, one patient case manager,
      medical director for QI, clinical QI consultant and director of clinical QI)
      involved in UQC at the PICU. Findings Individual, unit and organizational level
      factors were identified as influencing the function of the UQC. Leadership and
      work culture were the key facilitating factors to success and lack of QI training
      and personnel/dedicated time were perceived barriers to completing the QI
      initiative. Originality/value The findings from this research illustrate that
      frontline UQC are able to impact positive sustained change early in their
      establishment as part of a larger QMF. It is important, however, for the system
      to foster ongoing development of capacity and capability of these frontline UQC
      to ensure sustained success of the larger systems change.

PMID- 27707148
TI  - A randomised study of leadership interventions for healthcare managers.
AB  - Purpose The purpose of this paper was to assess two different leader development
      interventions by comparing their effects on leadership behaviour and evaluating
      their combined impact after two years, from the viewpoints of both the
      participating managers and external raters. Design/methodology/approach The study
      was a longitudinal randomised controlled trial with a cross-over design. Health
      care managers ( n = 177) were first randomised to either of two 10-month
      interventions and a year later were switched to the other intervention.
      Leadership behaviour was rated at pre-test and 12 and 24 months by participating
      managers and their superiors, colleagues and subordinates using a 360-degree
      instrument. Analysis of variance and multilevel regression analysis was
      performed. Findings No difference in effect on leadership behaviour was found
      between the two interventions. The evaluation of the combined effect of the
      interventions on leadership behaviour showed inconsistent (i.e. both increased
      and decreased) ratings by the various rater sources. Practical implications This
      study provides some evidence that participation in leadership development
      programmes can improve managers' leadership behaviours, but the results also
      highlight the interpretive challenges connected with using a 360-degree
      instrument to evaluate such development. Originality/value The longitudinal
      randomised controlled design and the large sample comprising both managers and
      external raters make this study unusually rigorous in the field of leadership
      development evaluations.

PMID- 27707149
TI  - The implementation of problem-based learning in health service management
      training programs.
AB  - Purpose Strengthening management capacity within the health care sector could
      have a significant impact on population health. However, many training programs
      in this area are still delivered using a classic lecture-based approach. The
      purpose of this paper is to evaluate and better understand the feasibility of
      using a problem-based learning (PBL) approach in health services management
      training programs. Design/methodology/approach A PBL teaching approach (based on
      the Maastricht University model) was tested with second-year postgraduate
      students from the Master in Public Health Management program at the Lithuanian
      University of Health Sciences. Students' opinions about PBL were investigated
      using a questionnaire with eight open-ended questions. Thematic content analysis
      was chosen to reflect the search for patterns across the data. Findings
      Respondents stated that the main advantage of PBL was that it was a more
      interesting and effective way of learning: "It is easier to remember, when you
      study by yourself and discuss with all peers". In addition, it was mentioned that
      PBL initiated a rapid exchange of ideas and sharing of personal experience.
      Students stressed that PBL was a good tool for developing other skills as well,
      such as "public speaking, communication, logic thinking". All students
      recommended delivering all other courses in the health services management
      program using PBL methodologies. Originality/value Findings from our study
      suggest that PBL may be an effective approach to teaching health services
      management. Potential problems in implementation are noted.

PMID- 27707150
TI  - The need for leadership training in long-term care settings.
AB  - Purpose Globally, in 1980, approximately 5.8 per cent of the world population was
      65 years old and older. By 2050, this number will more than triple to 16 per
      cent. From a leadership perspective, there is at least one challenge (among many
      others challenges) to consider. This paper (viewpoint) aims to provide support
      for the growing need for academically prepared managers.
      Design/methodology/approach This paper is a viewpoint which presents several
      characteristics of the long-term care (LTC) field that support the need for
      academically trained leaders. Findings LTC leaders in all countries must be
      sufficiently versed in numerous management areas to provide leadership when
      called on by those assigned to their care. Given local area variations in
      population needs present across all countries, it may be unwise to advocate for
      national, countrywide standardization of requirements. Yet, older adults
      accessing LTC services should expect a minimum level of knowledge from all of
      their providers - not just those who provide direct, hands-on care. However,
      similar to those who provide direct care, leaders should receive competency-based
      education with specific attention to effective communication skills, team-based
      approaches to care delivery, information technologies and population health.
      Originality/value Although much of the extant literature focuses on the delivery
      of care to older persons, there is a dearth of literature addressing the role of
      LTC leaders in light of global aging. Establishing a minimum level of academic
      training and increasing transparency focused on the positive experiences of
      elders residing in LTC facilities should help dispel the notion that placement in
      an LTC facility reflects filial failure.

PMID- 27707151
TI  - Addressing current and future challenges for the NHS: the role of good
      leadership.
AB  - Purpose This paper aims to describe and analyse some of the ways in which good
      leadership can enable those working within the National Health Service (NHS) to
      weather the changes and difficulties likely to arise in the coming years, and
      takes the format of an essay written by the prize-winner of the Faculty of
      Medical Leadership and Management's Student Prize. The Faculty of Medical
      Leadership and Management ran its inaugural Student Prize in 2015-2016, which
      aimed at medical students with an interest in medical leadership. In running the
      Prize, the Faculty hoped to foster an enthusiasm for and understanding of the
      importance of leadership in medicine. Design/methodology/approach The Faculty
      asked entrants to discuss the role of good leadership in addressing the current
      and future challenges faced by the NHS, making reference to the Leadership and
      Management Standards for Medical Professionals published by the Faculty in 2015.
      These standards were intended to help guide current and future leaders and were
      grouped into three categories, namely, self, team and corporate responsibility.
      Findings This paper highlights the political nature of health care in the UK and
      the increasing impetus on medical professionals to navigate debates on austerity
      measures and health-care costs, particularly given the projected deficit in NHS
      funding. It stresses the importance of building organisational cultures prizing
      transparency to prevent future breaches in standards of care and the value of
      patient-centred approaches in improving satisfaction for both patients and staff.
      Identification of opportunities for collaboration and partnership is emphasised
      as crucial to assuage the burden that lack of appropriate social care places on
      clinical services. Originality/value This paper offers a novel perspective - that
      of a medical student - on the complex issues faced by the NHS over the coming
      years and utilises a well-regarded set of standards in conceptualising the role
      that health professionals have to play in leading the NHS.

PMID- 27707153
TI  - Conferences.

PMID- 27707154
TI  - Vantage point.
AB  - DO YOU REMEMBER what you thought about nursing managers when you were a junior
      staff nurse? 'Suits,' we all said. 'They spend all their time in their offices.
      God alone knows what they do all day.' This set me thinking. What do I do all
      day? How do I explain it to a junior staff nurse?

PMID- 27707152
TI  - TQM and lean strategy deployment in Italian hospitals.
AB  - Purpose This paper aims to contribute to the debate concerning total quality
      management (TQM)-Lean strategy in public healthcare by analyzing the deployment
      path for implementation, the possible benefits that can be achieved and the
      encountered pitfalls. Design/methodology/approach Three case studies are drawn
      from three large Italian hospitals with more than 500 beds each and structured
      with many departments. The hospitals are located in Tuscany, Italy. These three
      hospitals have embraced TQM and Lean, starting from strategic objectives and
      their deployment. At the same time, they have also implemented many TQM-Lean
      tools. The case studies are based on interviews held with four managers in each
      of these three public hospitals. Findings Results from the interviews show that
      there is a specific deployment path for TQM-Lean implementation. The hospitals
      have also achieved benefits linked to patient satisfaction and improved
      organizational performances. Problems related to organizational and cultural
      issues, such as senior managers' commitment, staff management, manufacturing
      culture and tools adaptation, could affect the benefits. Research
      limitations/implications The research has been carried out in just three Italian
      public hospitals. Hence, similar investigations could be managed in other
      countries. Researchers could also use a larger sample and investigate these
      issues by means of quantitative inquiry. Practical implications Practitioners
      could try to apply the deployment path revealed by these case studies in other
      public and private hospitals. Originality/value The results of this research show
      that there is a specific, new deployment path for implementing TQM-Lean strategy
      in some public hospitals.

PMID- 27707156
TI  - Nurse nurse.

PMID- 27707155
TI  - Planning ward nursing: legacy or design?
AB  - FOR WARD MANAGERS trying to balance the demands of financial and clinical
      governance, any report that offers potential benchmark information and a critique
      of both strengths and weaknesses across a range of specialties must be a good
      thing. Well, per- haps not.

PMID- 27707157
TI  - Nurses could 'lose out' on leadership training.
AB  - Research findings published in this month's Nursing Management suggest that
      nurses may 'lose out' on leadership training following the abolition of the NHS
      national nursing leadership programme.

PMID- 27707159
TI  - On the move round up- wales.
AB  - Last month marked the launch of 22 local health boards (LHBs) across Wales. Their
      nurse directors come from a variety of backgrounds, not just the former local
      health groups (LHGs).

PMID- 27707158
TI  - End of life issues.
AB  - A new website with information on the difficult subject of end of life issues has
      been launched; www.EndofLifeIssues.org.uk The site collates information on topics
      such as euthanasia, treatment and living wills. A range of clinical and legal
      sources brings together current research, legislation and opinion on the subject.
      Site visitors can also take part in a confidential survey that aims to reflect
      the views and experiences of health professionals involved in this area of
      patient care.

PMID- 27707160
TI  - Foundation trusts to offer 'greater opportunities'.
AB  - Foundation status for health service trusts are set to empower senior nurses,
      delegates at the NHS leadership centre's annual conference heard last month.

PMID- 27707162
TI  - Extended formulary nurse prescribing courses.
AB  - Courses for 'extended formulary' nurse prescribing have been running since
      January, and the formulary is due to be extended further. Nurse executive
      directors and primary care trust lead nurses are being encouraged to look
      carefully at their workforces and services. If they decide that supplementary
      prescribing partnerships can improve services or put team skills to better use,
      they should nominate nurses for the centrally funded training. Details are
      available at www.doh.gov.uk/supplementaryprescribing.

PMID- 27707161
TI  - Modern matron roll out wins RCN support.
AB  - RCN general secretary Beverly Malone last month voiced her support for the
      government's modern matron initiative as it was extended to emergency departments
      across England.

PMID- 27707163
TI  - Feedback cuts sick rates.
AB  - Nursing managers can reduce absentee rates by giving feedback to staff on how
      often and how long they claim sick leave.

PMID- 27707164
TI  - Improving working lives.
AB  - The Improving Working Lives strategy remains at the heart of the government's
      drive to recruit and retain staff in the NHS, writes Steven Black.

PMID- 27707165
TI  - Human resource policies failing older nurses.
AB  - Human resource policies are failing nurses aged more than 50 despite government
      initiatives to retain experienced staff and encourage others to return to
      practice.

PMID- 27707166
TI  - As targets become more difficult to meet, the processes employed to achieve them
      will become less and less 'liberal'.
AB  - The Budget is usually big news. It is a source of debate among managers, at least
      until the health secretary has given his version of what it means for health
      care. Not so this year. Despite chancellor Gordon Brown giving one of his longer
      speeches, the event was almost completely subsumed by the coverage of the war in
      Iraq. Not that Nursing Management is disinterested in the military; an interview
      published in this issue with the army's leading nurse testifies to the journal's
      interest in all aspects of nursing leadership.

PMID- 27707168
TI  - Single use devices.
AB  - Love it or loathe it, European regulation of the workplace cannot be ignored. The
      re-use of single use medical devices is back on the agenda following an
      announcement that the European Commission's medical devices directive is to be
      reviewed.

PMID- 27707167
TI  - Research shows benefits of nurse leadership training.
AB  - Research from the UK and north America has helped confirm the value of nurse
      leadership training on both staff and patients.

PMID- 27707169
TI  - NHS leadership project.
AB  - The NHS leadership project website has a collection of externally developed
      leadership resources that may be useful. Go to
      www.nursingleadership.co.uk/resourc/r_tools.htm for information on tools for
      building anddeveloping teams, involving team members, problem solving, developing
      team learning cultures, improving team performance, and working with the people
      we serve. The site also has a ward staffing budgets workbook, which can be
      downloaded in Adobe Acrobat format, to help ward sisters and charge nurses manage
      budgets better.

PMID- 27707170
TI  - Nursing service.
AB  - IF FLORENCE NIGHTINGALE has a true professional nursing descendant, it is surely
      Director of Army Nursing Services and Matron-in- Chief of Queen Alexandra's Royal
      Army Nursing Corps (QARANC), Colonel Kathy George.

PMID- 27707171
TI  - New maternity arrangements.
AB  - New babies can make for happy times but since April 6 parents can feel even
      happier with the new statutory maternity arrangements.

PMID- 27707172
TI  - CNO monthly bulletin.
AB  - If you are a nurse director and want to receive the English chief nursing
      officer's monthly bulletin direct to your desktop, you can subscribe by emailing
      a request to dh-test-emails@doh.gsi.gov.uk Other nurses, midwives and health
      visitors should send email requests to doh_cno_subscription@talkingnumbers.com
      You should include details of the email address you want to use, your name, job
      title, the full name of your organisation, full postal address with postcode,
      plus phone and fax numbers. These details will be stored on a DoH database for
      future bulletin mailings.

PMID- 27707174
TI  - Conferences.
AB  - The college's fifth international nursing research conference to encourage
      sharing, collaboration and learning. It aims to bring together nurses from
      diverse clinical, academic and national settings to develop research based
      nursing knowledge and improve clinical effectiveness at all levels.

PMID- 27707173
TI  - On the move round up.
AB  - Promotions / new appointments.

PMID- 27707175
TI  - Nurse nurse.

PMID- 27707176
TI  - ?
AB  - Drama lessons: consultant nurse in general surgery Brigid Reid is among the
      winners of The Health Foundation's leading practice through research award
      scheme. The award will allow Ms Reid, who works at East Lancashire Hospitals NHS
      Trust, to undertake research to evaluate 'the use of dramatised patient
      experiences to facilitate interpersonal skills development in nurses'. She will
      also be able to develop her Drama lessons: consultant nurse in general surgery
      Brigid Reid is among the winners of The Health leadership skills through personal
      development training. The leading practice through research scheme will be
      calling for new applications from March 15. For further details, access
      www.health.org.uk.

PMID- 27707177
TI  - 'Standards' not 'targets' to underpin trust ratings.
AB  - Nursing leaders have cautiously welcomed government proposals to overhaul how NHS
      trusts are awarded their star ratings.

PMID- 27707178
TI  - First steps of the journey:job evaluation for agenda for change.
AB  - (JE) is probably the first Agenda for Change (AfC) activity that trusts will
      undertake: the starting point of a long journey to modernise pay and grading
      locally.

PMID- 27707179
TI  - CNO joins debate on racism.
AB  - England's chief nursing officer has said local employers should decide whether to
      adopt RCN recommendations on eradicating racism.

PMID- 27707180
TI  - NHS confederation opens doors to voluntary and independent sectors.
AB  - The NHS Confederation is extending its affiliate membership to voluntary and
      independent sector providers of health and social services.

PMID- 27707181
TI  - Editorial.
AB  - When diacnostic related groups were emerging in the US healthcare reforms of the
      1970s, we in the UK took the moral high ground. They smacked of payment by
      results, we said.

PMID- 27707182
TI  - Nurse morale improved in UK magnet hospital.
AB  - Nurses' morale at the UK's only magnet hospital has improved markedly despite an
      increase in workload and working hours.

PMID- 27707183
TI  - Consent to clinical decisions when capacity is absent. part 1: Making decisions.
AB  - IN JUNE last year, the government announced its intention to publish a Mental
      Incapacity Bill. The bill is now published in draft form and aims to give people
      with impaired capacity in England and Wales the same legal protection already
      enjoyed by people in Scotland.

PMID- 27707184
TI  - National procedure tariffs fail to reflect patient dependency.
AB  - A new national tariff for clinical procedures fails to reflect patient
      dependency, senior nurses have been warned.

PMID- 27707185
TI  - Redesigning roles.
AB  - Are you facing problems with service and role redesign? Need a helping hand to
      change the way your organisation works? Then help is available from a database
      compiled by the NHS Modernisation Agency.

PMID- 27707187
TI  - Employment equality.
AB  - Two new sets of employment regulations that came into force at the end of last
      year are now available on the internet, writes Steven Black. The Employment
      Equality (Religion or Belief) Regulations 2003 are available at
      www.legislation.hmso.gov.uk/si/si2003/20031660.htm and The Employment Equality
      (Sexual Orientation) Regulations 2003 are at
      www.legislation.hmso.gov.uk/si/si2003/20031661.htm.

PMID- 27707186
TI  - Vantage point.
AB  - As a younger I used to visit families in France and Germany on exchange
      programmes, and my large family welcomed a steady stream of European young people
      in return. The exchanges broadened our horizons and showed us that we had much in
      common despite our cultural differences.

PMID- 27707188
TI  - On the move round up.
AB  - Promotions / new appointments.

PMID- 27707190
TI  - Health in the workplace.
AB  - The centre for occupational health and safety at Heriot-Watt University,
      Edinburgh, has put together an online course for those involved in health and
      safety, occupational health, workplace health promotion, human resources or trade
      union representation. It can be accessed at www.hw.ac.uk/cohs/wh.htm.

PMID- 27707189
TI  - Nurse prescribing education.
AB  - Meanwhile, NHS Education for Scotland has launched an interactive online learning
      resource to support nurse prescribing educational programmes. Developed by a team
      from The Robert Gordon University, Aberdeen, the site provides 24-hour access to
      online open learning materials and is available to all higher education
      institutions.

PMID- 27707191
TI  - Coast to coast media friendly.
AB  - SEVERAL WEEKS ago, in preparing to write this article, I decided to carry out a
      test. For a week, I scrutinised the four newspapers that arrive at our doorstep
      every day. I also scrutinised TV and radio news, and as many of the prime time
      dramatic series as I could. I was looking for nurses of course.

PMID- 27707192
TI  - International nurse recruitment.
AB  - The Department of Health has published a website intended to guide nurse managers
      around the ethical and logistical pitfalls of international nurse recruitment.

PMID- 27707193
TI  - Self paced, self based.
AB  - Leeds Metropolitan University and computer based learning specialists Scheidegger
      Training have established the Scheidegger Institute to boost continuing
      professional development for healthcare professionals. Its website address is
      www.scheideggerinstitute.com.

PMID- 27707194
TI  - Psychotic-Like Speech in Frontotemporal Dementia.
AB  - Behavioral variant frontotemporal dementia (bvFTD) may result in psychotic-like
      speech without other psychotic features. The authors identified a bvFTD subgroup
      with pressure of speech, tangentiality, derailment, clanging/rhyming, and punning
      associated with the right anterior temporal atrophy and sparing of the left
      frontal lobe.

PMID- 27707196
TI  - Depressive Symptoms Contribute to Executive Deficits in Temporal Lobe Epilepsy.
AB  - This study examined the contribution of depression to reduced executive
      functioning in temporal lobe epilepsy (TLE) using three groups: TLE only (TLE;
      N=29), TLE+depression (TLE+DEP) (N=22), and nonneurologic participants with
      depression (DEP; N=31). Participants completed the Delis-Kaplan Executive
      Function System. Individuals with TLE performed worse than the DEP group on many
      tests of executive functions. Among the TLE participants, those with depression
      demonstrated poorer executive functioning. These findings support the notion that
      depression may further contribute to executive difficulties in individuals with
      TLE. Depression treatment in this population could lead to improvements in
      cognition.

PMID- 27707195
TI  - Effect of High-Frequency Transcranial Magnetic Stimulation on Craving in
      Substance Use Disorder: A Meta-Analysis.
AB  - Repetitive transcranial magnetic stimulation (rTMS), a noninvasive,
      neuromodulatory tool, has been used to reduce craving in different substance use
      disorders. There are some studies that have reported conflicting and inconclusive
      results; therefore, this meta-analysis was conducted to evaluate the effect of
      high-frequency rTMS on craving in substance use disorder and to investigate the
      reasons behind the inconsistency across the studies. The authors searched
      clinical trials from MEDLINE, Cochrane databases, and International Clinical
      Trials Registry Platform. The PRISMA guidelines, as well as recommended meta
      analysis practices, were followed in the selection process, analysis, and
      reporting of the findings. The effect estimate used was the standardized mean
      difference (Hedge's g), and heterogeneity across the considered studies was
      explored using subgroup analyses. The quality assessment was done using the
      Cochrane risk of bias tool, and sensitivity analysis was performed to check the
      influences on effect size by statistical models. After screening and assessment
      of eligibility, finally 10 studies were included for meta-analysis, which
      includes six studies on alcohol and four studies on nicotine use disorder. The
      random-model analysis revealed a pooled effect size of 0.75 (95% CI=0.29 to 1.21,
      p=0.001), whereas the fixed-model analysis showed a large effect size of 0.87
      (95% CI=0.63 to 1.12, p<0.00001). Subgroup analysis for alcohol use disorder
      showed an effect size of -0.06 (95% CI=-0.89 to 0.77, p=0.88). In the case of
      nicotine use disorder, random-model analysis revealed an effect size of 1.00 (95%
      CI=0.48 to 1.55, p=0.0001), whereas fixed-model analysis also showed a large
      effect size of 0.96 (95% CI=0.71 to 1.22). The present meta-analysis identified a
      beneficial effect of high-frequency rTMS on craving associated with nicotine use
      disorder but not alcohol use disorder.

PMID- 27707218
TI  - Involving Older People in Research: 'An Amateur Doing the Work of a
      Professional?' Peace Sheila Involving Older People in Research: 'An Amateur Doing
      the Work of a Professional?' 48pp L8 1 90109 725 0 1901097250.
AB  - Researchers are increasingly required to address issues of user participation
      within their work. This volume describes ways in which older people can
      participate in research projects as originators of research questions, advisers
      on methodology, analysts of data, fieldworks and disseminators of findings.

PMID- 27707197
TI  - Location of Acute Infarcts and Agitation and Aggression in Stroke.
AB  - The role of the infarct location in the development of poststroke agitation (PSA)
      is largely unknown. This study examined the association between the locations of
      infarcts and PSA at 9 months following the index stroke in 213 patients with the
      Chinese version of the Neuropsychiatric Inventory. Compared with the non-PSA
      group, PSA patients had a higher number and volume of acute pontine infarcts.
      Ventral pontine and lateral cerebellar infarcts were independent predictors of
      PSA in the multivariate analysis.

PMID- 27707219
TI  - Biographical Interviews: The Link Between Research and Practice Biographical
      Interviews: The Link Between Research and Practice Joanna Bornat (Ed) 48pp L8 1
      90109 720 X 190109720X.
AB  - Biographical, life history and reminiscence-based approaches to health and social
      work with older people have demonstrated positive outcomes. Each of the authors
      in this study has developed biographical approaches to research and practice in
      original and creative ways. The aim of this book is to develop an awareness of
      the direct contribution that familiarity with a life history can make to good
      quality care practice.

PMID- 27707220
TI  - Joseph Rowntree Foundation publications.
AB  - In 2004 the Joseph Rowntree Foundation celebrates its centenary year. The JRF's
      older people's programme has been developed with, and mainly by, older people. It
      is about the lives of older people when they need 'that bit of help'. Some of
      this is about mainstream services, but mostly it is about older people's views of
      what helps them to live well in later life. JRF publications are available from
      York Publishing Services Ltd, 64 Hallfield Road, Layerthorpe, York YO31 7ZQ. Tel:
      01904 430033. Web: www.jrf.org.uk/bookshop.

PMID- 27707221
TI  - 'Let's move on.' black and minority ethnic older people's views on research
      findings Butt Jabeer and O'Neil Alex 'Let's Move On.' Black and Minority Ethnic
      Older People's Views on Research Findings L11.95 1 85935 175 1 1859351751.
AB  - This report is based on consultation and discussion with older people from black
      and minority ethnic communities in Leeds, Bristol and London. It shows how older
      people from different communities experience a shared sense of exclusion from
      mainstream communities and practical steps for researchers, policy makers and
      practitioners to involve older people in setting local or national agendas.

PMID- 27707222
TI  - A survival guide to later life: how to stay healthy, happy, mobile and in control
      Shoard Marion A survival guide to later life: how to stay healthy, happy, mobile
      and in control Robinson Publishers L9.99 1 84119 372 0 1841193720 [Formula: see
      text].
AB  - The author is a layperson, writing from the experience of caring for her mother
      as her health declined. Along the way she learned a great deal and this book sets
      out to share that knowledge. There is no question that this is an ambitious
      project and what it may lack in terms of detail in some respects, it makes up for
      in other ways.

PMID- 27707223
TI  - Moving and handling Moving and Handling Leslie Helen MacKenzie Rob Dementia
      Services Development Centre L10 [Formula: see text].
AB  - Produced by the Dementia Services Development Centre, this book is not intended
      as a comprehensive guide to moving and handling. Rather it aims to highlight a
      few issues that are particularly problematic for people with dementia.

PMID- 27707225
TI  - Grants for nursing projects.
AB  - The Burdett Trust for Nursing, an independent charitable trust named after Sir
      Henry Burdett KCB, founder of the Royal National Pension Fund for Nurses, offers
      grants for projects that are nurse-led. Applications must focus explicitly on
      improving care for patients through nursing and may include multi-professional or
      team-working interventions (clinical care, environment of care, leadership,
      education and research).

PMID- 27707226
TI  - Learning to speak Alzheimer's Joanne Koenig Coste Learning to Speak Alzheimer's
      Vermilion 256pp L9.99 0091886724 0091886724 [Formula: see text].
AB  - The strength of this book comes from the personal journey of discovery that the
      author has taken to arrive at her ideas and model of care. This personal style
      includes the reader in Joanne Koenig Coste's traumatic early acknowledgment that
      her husband had developed dementia and her later sense of isolation when there
      seemed so little help around. This seems to have fired her to work in the field,
      agitate for change and write of her experiences.

PMID- 27707227
TI  - Centre for policy on ageing publications Julia Johnson Centre for Policy on
      Ageing publications 112pp L10.00 1 90109 755 2 1901097552 Writing Old Age.
AB  - Four publications based on seminars hosted jointly by the CPA and the Centre for
      Applied Biological Studies are now available from: Central Books, 99 Wallis Road,
      London E9 5LN. Tel: 0845 458 9910. Email (mail order): mo@centralbooks.com Web:
      www.centralbooks.co.uk.

PMID- 27707228
TI  - Everyday Living in Later Life Bytheway Bill Everyday Living in Later Life 96pp
      L10.00 1 90109 770 6 1901097706.
AB  - How do older people get through their days? This book discusses how we should
      research the routines of everyday living and place this evidence in the broader
      context of the experience of ageing. The contributors explore themes regarding
      the mundane nature of everyday ageing life: discrepancies arising from surveys
      and interviews in detailing daily activities, eating habits, managing medication
      and more general events of daily living.

PMID- 27707229
TI  - Time to Remember: Introducing Reminiscence into Elderly Care Time to Remember:
      Introducing Reminiscence into Elderly Care McLean Valerie 112pp L19.95 0 95303
      291 4 0953032914.
AB  - Reminiscence activities have become a widely accepted feature of many settings
      where older people are nursed. Memories of the past represent a valuable resource
      which can be used to facilitate personcentred care, improve social interaction,
      or simply provide the theme for an hour's activity.

PMID- 27707230
TI  - Ignorance and fear inhibit older people's care, says 'tsar'.
AB  - Ian Philp, the older people's 'tsar', has hit back at those who say the specialty
      involves little more than 'basic care'.

PMID- 27707231
TI  - 'Getting Old is Not for Cowards.' Literature on Comfortable Healthy Ageing Reed
      Jan Cook Glenda Childs Susan and Hall Amanda 'Getting old is not for cowards.'
      literature on comfortable healthy ageing L8.95 1 85935 121 2 1859351212.
AB  - This literature review considers different ideas about ageing. It explores how
      growing older is conceptualised, including polarised views that see old age
      either as inevitable decline with efforts made to identify ways of coping, or as
      an enemy to be fought, with submission to its effects viewed as defeat and
      failure. Reviewing an extensive and diverse range of literature, it suggests that
      a new concept of older age may be needed and highlights areas for further
      research.

PMID- 27707233
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27707234
TI  - Competition watchdog will examine care homes sector.
AB  - The Office of Fair Trading (OFT) is to investigate the care homes sector and
      examine ways in which older people make choices about a care home and how these
      affect competition in the market. The move follows a 'super-complaint' by the
      Consumers' Association which highlighted concerns about the care home sector in
      England. But groups representing care homes have said the OFT inquiry will not go
      far enough because it will not investigate fees paid by local authorities.

PMID- 27707235
TI  - Use of physical restraints with cognitively impaired nursing home residents.
AB  - The issue of whether restraints should be used in nursing home settings in order
      to reduce the number of injuries resulting from falls remains controversial on a
      world-wide basis. In this Dutch study, the care of 265 residents was examined. It
      was found that restraints were used with 49 per cent of residents, the most
      frequently encountered being bed rails, belts, and 'geriatric' chairs with a
      table attached. The most common reason given by nursing staff for the use of
      restraints was the prevention of falls, followed by a need to control
      restlessness, and to allow the safe use of medical devices. A novel aspect of
      this study was that four members of staff volunteered to experience the use of
      restraints for themselves during a 24- hour period. They reported a complete
      absence of privacy and freedom of movement, together with physical discomfort.
      The authors conclude that there is a need to review the use of such restraints in
      all their aspects.

PMID- 27707236
TI  - Older patients with chronic heart failure within Swedish community health care: a
      record review of nursing assessments and interventions.
AB  - Nursing records can provide a valuable source of information for the researcher.
      In this study, community nursing records for two periods of two years were
      reviewed retrospectively in order to locate and analyse statements relating to
      the monitoring of patients with chronic heart failure. The older people being
      studied were drawn from nursing homes, specialist housing for older people, and
      those living in their own homes. The total number of records included in the
      sample was 161, and appropriate instruments were used to collect the data in a
      systematic manner. However, the records were found to be largely ordered in a
      chronological sequence, and written in a narrative form, but without a shared
      format or structure. Drug administration was the most commonly recorded nursing
      intervention, while only 12 per cent of records indicated that patients were
      being weighed, and 3 per cent recorded health promotion activities.

PMID- 27707237
TI  - Cognitive therapy integrated with life review techniques: an eclectic treatment
      approach for affective symptoms in older adults.
AB  - This paper describes an advanced practice mental health nurse's experience of
      combining the two distinct psychotherapeutic approaches into one treatment
      strategy for a group of older people in an American outpatient psychotherapy
      clinic. The main issue being experienced by the participants was unresolved grief
      following the death of a partner. By the end of the 12-week process, six of the
      seven group members were reporting an improvement which was sufficient to enable
      them to be discharged from treatment.

PMID- 27707238
TI  - Factors associated with variations in older people's use of community-based
      continence services.
AB  - The fact that a service is available provides no guarantee that those who would
      benefit from it will actually use it, and that is especially the case for those
      with stigmatising conditions such as urinary incontinence. This study involved a
      cross-sectional postal survey of patients aged over 65 who were registered with
      four general practices in a socially deprived urban area (n=1,376). The overall
      response rate was 66 per cent. The proportion of the sample reporting urinary
      leakage was 39 per cent, although only 15 per cent had accessed relevant
      services. The authors suggest that contacts with the primary care team should be
      used to explore the issue of urinary incontinence through the use of a validated
      assessment instrument.

PMID- 27707239
TI  - Website watch.
AB  - The Centre for Policy on Ageing (CPA) has launched a new training resources
      website for health and social care practitioners implementing the single
      assessment process (SAP) for older people from this month.

PMID- 27707240
TI  - Developing the gerontology practitioners network in wales.
AB  - This network aims to act as an all-Wales focus for nurses interested in or
      working with older people. It aims to promote a positive image of ageing, raise
      the profile of the contribution of nursing to care and support of older people in
      all care environments, improve understanding of the nursing contribution within
      the unified assessment, act as an expert resource for older people and influence
      policies affecting the health and care of older people in Wales.

PMID- 27707241
TI  - Milestones mark progress to better care.
AB  - It is said that history never feels like history when you are living through it,
      so this month, as we pass some milestones on the journey of older people's care,
      it seems timely to consider our past and our future.

PMID- 27707242
TI  - Falls-prevention initiative to go nationwide.
AB  - An initiative designed to reduce falls among older people is to be rolled out
      nationally after pilot projects showed that multi-agency teams could help cut
      their incidence by a third.

PMID- 27707243
TI  - ?
AB  - Older patients at Springfield Hospital in south London have been taking part in
      an interactive drama project with theatre company Ladder to the Moon.
      Professional actors play an American film director and aspiring Tooting actress
      'Betty O'Brien' in a production that involves searching the wards for extras,
      opinions and inspiration. Nurses and a reminiscence consultant helped patients
      create themes and scenarios.

PMID- 27707244
TI  - Reid calls for 'big debate' over public health.
AB  - Nurses working with older people have until the end of May to respond to the
      government's new consultation paper on improving public health.

PMID- 27707246
TI  - Commentary.
AB  - It is a pleasure and a privilege to be asked to write the first of these new
      style commentaries in Nurse Researcher. My reflections introduce four papers
      exploring post-colonial and minority ethnic issues in nursing and health-related
      research (pages 7-67).

PMID- 27707247
TI  - Editorial.
AB  - The long-awaited results of last year's research assessment exercise (RAE)
      received mixed reactions. However, we at Nurse Researcher feel there is much to
      be celebrated. More nursing departments were considered in the exercise than in
      the previous assessment, larger groups of staff were entered from individual
      establishments and overall scores improved substantially (for more information
      see the RAE website: www.rae.ac.uk ).

PMID- 27707248
TI  - Practical Psychiatry of Old Age 3rd edition John P Wattis Practical Psychiatry of
      Old Age 3rd edition Stephen Curran Radcliffe 268pp L24.95 1 85775 245 7
      1857752457 [Formula: see text].
AB  - This very accessible and well-written book is perfectly described as a 'primer'
      for those interested in the field of old age psychiatry, addressing as it does
      the key issues within the target subject. The main intended audience is that of
      the medical student in training or the aspiring medical practitioner early in his
      or her career.

PMID- 27707245
TI  - RENEB - Running the European Network of biological dosimetry and physical
      retrospective dosimetry.
AB  - PURPOSE: A European network was initiated in 2012 by 23 partners from 16 European
      countries with the aim to significantly increase individualized dose
      reconstruction in case of large-scale radiological emergency scenarios. RESULTS:
      The network was built on three complementary pillars: (1) an operational basis
      with seven biological and physical dosimetric assays in ready-to-use mode, (2) a
      basis for education, training and quality assurance, and (3) a basis for further
      network development regarding new techniques and members. Techniques for
      individual dose estimation based on biological samples and/or inert personalized
      devices as mobile phones or smart phones were optimized to support rapid
      categorization of many potential victims according to the received dose to the
      blood or personal devices. Communication and cross-border collaboration were also
      standardized. To assure long-term sustainability of the network, cooperation with
      national and international emergency preparedness organizations was initiated and
      links to radiation protection and research platforms have been developed. A legal
      framework, based on a Memorandum of Understanding, was established and signed by
      27 organizations by the end of 2015. CONCLUSIONS: RENEB is a European Network of
      biological and physical-retrospective dosimetry, with the capacity and capability
      to perform large-scale rapid individualized dose estimation. Specialized to
      handle large numbers of samples, RENEB is able to contribute to radiological
      emergency preparedness and wider large-scale research projects.

PMID- 27707250
TI  - Good ideas - poor experiences.
AB  - This month sees the publication of a range of new policies, guidance and
      standards aiming for better services for older people.

PMID- 27707251
TI  - Regulations laid out by new commission.
AB  - Proposed new registration regulations for independent health care services have
      been laid out by the Department of Health.

PMID- 27707253
TI  - Involving Relatives and Friends: A Good Practice Guide for Homes for Older People
      Julia Burton-Jones Involving Relatives and Friends: A Good Practice Guide for
      Homes for Older People The Relatives and Residents Association 5 Tavistock Place
      London WC1H 9SN 57pp L8 + L2 1-900216 02 7 1900216027.
AB  - This is a super book which is detailed, straightforward and well illustrated. The
      author's strong desire to see home environments which enable existing
      relationships between residents and their families to continue is apparent
      throughout the text.

PMID- 27707254
TI  - A shared experience.
AB  - Rey, Hilda and Agnes arrived from the Philippines to work in our nursing home in
      Carrickfergus last year. The senior staff at Tamlaght were keen to make sure the
      nurses were not too homesick and, although the bitterly cold Northern Irish
      winter was a long way from the warm climate of their home country, the natural
      warmth of the Irish hospitality helped, and they enjoyed the 'craic' with other
      young members of staff.

PMID- 27707256
TI  - Website watch.

PMID- 27707255
TI  - ?
AB  - Time has gone so fast and we have been at Tamlaght for nearly a year. These past
      months have been full of challenges, realisations and experiences - a variety of
      good and bad days but so worthwhile to learn from.

PMID- 27707257
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27707258
TI  - Physical functioning of elderly cancer patients prior to diagnosis and following
      initial treatment.
AB  - This American study used a well- known tool, the SF-36, to measure the physical
      functioning of older people before and after cancer was diagnosed. The sample
      included patients with cancers of the breast, colon, lung and prostate, who were
      receiving treatment in community oncology departments. The findings indicated
      that site and stage of cancer prior to diagnosis did not affect functioning, but
      once treatment began, symptoms such as pain, fatigue and insomnia had a
      significant impact. 37 references.

PMID- 27707259
TI  - ?
AB  - This American study used a wellknown tool, the SF-36, to measure the physical
      functioning of older people before and after cancer was diagnosed. The sample
      included patients with cancers of the breast, colon, lung and prostate, who were
      receiving treatment in community oncology departments. The findings indicated
      that site and stage of cancer prior to diagnosis did not affect functioning, but
      once treatment began, symptoms such as pain, fatigue and insomnia had a
      significant impact. 37 references.

PMID- 27707260
TI  - 'He will finish up caring for me': people with learning disabilities and mutual
      care.
AB  - At the time of the last census, almost 90 per cent of people with learning
      disabilities were living in the community, and most received support from family
      members.

PMID- 27707261
TI  - Gnp update.
AB  - Some of the recent activity of the Gerontological Nursing Programme(GNP) has
      centred on developing a new strategy to cover the next three years. The strategy
      will be organised around four themes.

PMID- 27707262
TI  - The principle of respect for autonomy in the care of nursing home residents.
AB  - In this study of attitudes to autonomy held by Dutch nursing home managers and
      physicians, vignettes were used to ascertain their views. As the concept of
      autonomy itself is much debated by ethicists, the authors constructed the
      vignettes so that they epitomised four approaches to this principle.

PMID- 27707263
TI  - Overseas recruitment.
AB  - Recruiting nurses from overseas can be a solution for the acute staffing
      shortages experienced by nursing homes. But before accepting nursing home
      contracts, it is really important that they have a clear understanding of the
      values and skills required to work with older people and of the unique and
      privileged role that nurses fulfil in these settings.

PMID- 27707264
TI  - Bunis scoops award.
AB  - The Nursing Standard Nurse 2001 Nursing Older People award was won by Bunis
      Packham, who developed a nurse-led anti-coagulation service for older people in
      primary and secondary care at Barnett and Chase Farm NHS Trust in Hertfordshire.

PMID- 27707265
TI  - Tell the truth about dementia, says MHF.
AB  - Health professionals should tell people who develop dementia the truth about
      their diagnosis, says a report from the Mental Health Foundation (MHF).

PMID- 27707266
TI  - Inspection of inspectors reveals poor standards.
AB  - Health authority registration and inspection of nursing homes is haphazard and
      fails to provide systems that protect patients adequately, according to a report
      by the Social Services' Inspectorate (SSI).

PMID- 27707267
TI  - New publications.

PMID- 27707268
TI  - Letters.
AB  - I read the article 'Closing time' (September 2001) and felt very saddened for all
      concerned. Living and working in Worthing, West Sussex, I am well aware of the
      number of nursing homes that are closing, it seems, through no fault of their
      own.

PMID- 27707269
TI  - Components of a proper hospital discharge for elders.
AB  - The interface between hospital and community services for older people remains a
      crucial one, so research findings on the discharge process can have an important
      role to play. This qualitative study undertaken in south London was based on the
      analysis of 24 semi-structured interviews conducted with members of the multi
      disciplinary team (MDT), carers and older people themselves. The findings were
      generally positive.

PMID- 27707293
TI  - Handling qualitative data Lyn Richards Handling qualitative data Sage 224 L21.99
      0761942599 0761942599 [Formula: see text].
AB  - While many texts focus on theoretical perspectives and the methodological
      approaches associated with qualitative research, few offer insights into the
      actual 'doing' of qualitative research. The focus of this text 'handling
      qualitative data' will, I believe, be of great interest to nurse researchers,
      offering sound advice in an innovative format, based on the author's extensive
      research career. Throughout the text, graphic representations in the form of
      icons are used to indicate four underpinning threads which run throughout the
      book. These are.

PMID- 27707294
TI  - Introduction to the Practice of Statistics David Moore Introduction to the
      Practice of Statistics and George McCabe WH. Freeman 850 L39.99 071676282X
      071676282X [Formula: see text].
AB  - This is a very well-written and beautifully presented book. It is north American
      in origin and, while it will be invaluable for teachers of statistics to nurses
      and other healthcare professionals, it is probably not suitable for many preor
      post-registration students in health in the UK. The material is quite advanced
      and, while well illustrated, exemplified and with numerous examples for students,
      it takes a fairly mathematical approach in places. Nevertheless, the book has
      much to commend it, including a CD-ROM package containing tutorials, a
      statistical package, solutions based on the exercises in the text and case
      studies.

PMID- 27707295
TI  - Social research Sotirios Sarantakos Social research Palgrave Macmillan 500 L19.99
      1403943206 1403943206 [Formula: see text].
AB  - I found Sarantakos's book to be a clear and straightforward guide to social
      research methods. The book is aimed at undergraduate level, and I am sure will
      appeal to students from a range of disciplines. The structure of the book
      reflects the different stages of the research process and as such it is easy to
      locate all the required sections. It introduces qualitative and quantitative
      approaches in a balanced way and includes sufficient detail of the philosophical
      roots of each of these research traditions. It was good to find simple and easy
      to follow accounts of the complex underpinning of a number of research approach
      that are popular in nursing research. Included are topics such as interpretivism,
      symbolic interactionism and phenomenology as well the more usually found
      hallmarks of positivistic-type research. While feminism and feministic research
      in nursing is an important subject area I did wonder if the amount of attention
      they received were perhaps a little unbalanced when related to the other subject
      areas covered. There are, however, useful sections on data collection and
      analysis. I found, for example, the section on grounded theory approaches to data
      analysis particularly good.

PMID- 27707296
TI  - Making the most of opportunities..
AB  - When asked to contribute to the Making My Mark series, my immediate response was
      to agree. Once I had done so, I began to wonder what sort of mark I have actually
      made. For inspiration, I looked back at previous papers in the series, to
      establish where, in the grand scheme of things, my contribution to nursing and
      healthcare research might lie. I found papers written by both highly experienced
      and internationally known researchers and by those just starting out on a
      research career. My position lies somewhere between these two, and if I can
      borrow a term coined by a research collaborator, Dr Jeremy Segrott, University of
      Wales Swansea School of Health Care, I would describe myself as a 'midiphyte'
      (someone with postgraduate training and hands-on research experience, but who has
      yet to become a totally independent and self-supporting researcher). To borrow a
      term from another colleague, I also see myself as something of a 'butterfly';
      someone who is still defining a clear research niche and who has engaged with a
      number of different projects as the need or opportunity has arisen.

PMID- 27707297
TI  - Qualitative methods for health research J Judith Green Qualitative methods for
      health research and Nicki Thorogood Sage 280 L19.99 076194771X [Formula: see
      text].
AB  - When I first looked at this book I wondered if there was room for yet another
      title on qualitative research in health. Indeed, the authors point out that there
      are already many excellent introductory textbooks available on this topic.
      However they have identified similar gaps in the literature as I have in working
      particularly with postgraduate students and neophyte researchers. In my view,
      their book has largely been successful in filling the gaps.

PMID- 27707298
TI  - Research can be challenging, but it is always rewarding.
AB  - Research can be a scary business. For new researchers it may appear as a
      minefield to be entered as a necessity and negotiated with caution. For those of
      us who have some experience of research, there is the knowledge that each project
      brings with it a different set of challenges to be completed in what appears to
      be an ever-changing landscape. So, irrespective of whether you are a highly
      experienced nurse researcher, a novice or (like many of us) somewhere in between,
      the process of conducting research brings new opportunities and challenges. This
      constantly evolving landscape governs and influences many aspects of the research
      process from formulation of initial ideas, through ethical considerations, data
      collection, analysis and completion. To a great extent, success is dependent on a
      mixture of luck, judgement and determination.

PMID- 27707299
TI  - Ethical footprints: finding a way through the research process.
AB  - In common with other facets of modern life in the 21st century, the nursing
      research context is dynamic and constantly changing. It is not only the neophyte
      researcher who is required to keep abreast of current legislative regulations and
      frameworks that guide the conduct of research. More experienced researchers also
      require knowledge and understanding of contemporary research ethics and
      governance frameworks in order to conduct research and guide students. In
      designing, operationalising, reporting and disseminating research we ought to
      aspire to leave 'ethical footprints'. By this I mean that those researchers who
      follow in our research journey may tread in our foot- prints with the knowledge
      that the conduct of our research has been ethical.

PMID- 27707300
TI  - Resources for nursing research: an annotated bibliography Cynthia Clamp Resources
      for nursing research: an annotated bibliography et al Fourth Sage L50 Pages : 432
      0761949917 0761949917 [Formula: see text].
AB  - When this book landed on my desk I wasn't sure of its value. However, within a
      few days I had already found it extremely useful. The book will be a valuable
      resource for researchers at all stages of their careers. It acts as a starting
      point for those seeking information about a vast array of research-related
      topics. For example, if you want to know something about triangulation, a section
      that provides a definition is followed by a list of references and a few lines
      describing the content and usefulness of each reference. Should you be looking
      for information about a specific approach, an extensive list of references is
      provided about a broad range of methodologies.

PMID- 27707301
TI  - Triangulation as a method for contemporary nursing research.
AB  - The complex nature of phenomena investigated by nurses demands the use of a
      multifaceted approach to develop nursing knowledge. Triangulation offers a
      rigorous methodological framework by which to achieve this aim. The authors
      describe the historical and philosophical underpinnings of triangulation and
      outline considerations in relation to applying it in contemporary nursing
      research.

PMID- 27707302
TI  - Statistics for Health Care Professionals Ian Scott Statistics for Health Care
      Professionals and Debbie Mazhindu Sage 248 :L19.99 0761974768 0761974768
      [Formula: see text].
AB  - As a recent recruit to a lecturerpractitioner post with little recent experience
      in the subject area covered by this book, I found it met my needs very well.
      After all, this topic can be quite daunting for some. The 18 chapters are
      relatively short and I was able to dip into them when time allowed. However, it
      can also be read for extended periods, as the text is broken up with numerous
      information boxes, diagrams and tables. All the examples are relevant and
      appropriate to practice settings.

PMID- 27707303
TI  - Patient confidentiality, clinical data and NHS research - a researcher's guide.
AB  - More stringent research governance in the NHS has led to an increased focus on
      the importance of patient confidentiality. But relatively low levels of knowledge
      of the Data Protection Act and common law duty of confidentiality among some
      researchers and research managers cause difficulties in getting research projects
      off the ground. The authors outline the main issues surrounding research, data
      protection and patient confidentiality, and provide guidance for researchers,
      clinicians and managers on how to conduct research appropriately.

PMID- 27707304
TI  - Training Manual for Working with Older People in Residential and Day Care
      Settings Jackie Pritchard Training Manual for Working with Older People in
      Residential and Day Care Settings Jessica Kingsley Publishers 399pp L39.95 1
      843101238 1843101238 [Formula: see text].
AB  - With the requirement for training in care homes now firmly set in legislation, a
      plethora of resources has started spilling onto the market. This manual is
      another example of an imaginative approach offering home managers and trainers
      resources to move staff through the hoops that the induction and foundation
      standards have rapidly become.

PMID- 27707307
TI  - ?
AB  - Educational provision in nursing was once confined within national boundaries,
      but the development of the internet has encouraged the formation of international
      links. In this paper, the experience of delivering a course in gerontology
      developed by a Canadian School of Nursing through a partnership arrangement with
      a private university in Chile is described.

PMID- 27707308
TI  - Older homeless discharged with nowhere to go, say charities.
AB  - Older homeless people are being discharged from hospital even though they have no
      home to go to, according to a report by Help the Aged and the Housing
      Associations Charitable Trust (HACT). As a result, say the charities, older
      people are being sent to unsuitable mixed-age hostels.

PMID- 27707309
TI  - Exciting times for an important specialty.
AB  - Gerontological nursing is such an exciting specialty. Not only do we work with
      diverse people from different generations but the older population is constantly
      evolving and therefore, in order to remain effective, our practice must
      constantly evolve.

PMID- 27707310
TI  - Nurses working with older people scoop major awards.
AB  - Two nurses who work with older people have been included among the category
      winners in the Nursing Standard Nurse 2003 awards. From a record number of
      entries, Sharon.

PMID- 27707311
TI  - Care homes urge rethink over staff security checks.
AB  - Care home organisations were calling for an urgent rethink by government of
      security clearance for care home staff as Nursing Older People went to press. The
      joint action follows the withdrawal of guidance by the National Care Standards
      Commission (NCSC), which had allowed new workers to be employed while security
      checks were being undertaken. But the NCSC has now ended the 28-day grace period.

PMID- 27707312
TI  - Postoperative cognitive changes among older Taiwanese patients.
AB  - Delirium, sometimes known as acute confusion, poses a major challenge in the post
      operative care of many older people. For this study, 106 patients ranging in age
      from 65 to 93 (mean 73.9), and undergoing orthopaedic or urological surgery, were
      selected. Around 40 per cent of the sample subsequently developed delirium.
      Detailed measurements using the Mini Mental State Examination are reported.

PMID- 27707313
TI  - Prisoners' health: key concerns.
AB  - The vast majority of older people in prison suffer from long-standing illness or
      disability and more should be done to meet their health and social needs,
      according to a recent study.

PMID- 27707316
TI  - Comparison of quality of life measures in heart failure.
AB  - It is noticeable that the attention of clinical researchers worldwide is
      increasingly being focused upon the effects of heart failure, which in the past
      may not have had the attention given to other conditions. Despite a range of
      innovative treatments, morbidity and mortality rates in heart failure remain
      high. In this American study, the psychometric properties of three quality of
      life scales were compared. These were the Chronic Heart Failure Questionnaire
      (CHFQ), the Minnesota Living with Heart Failure Questionnaire (LHFQ), and the
      General Health Survey Short-form12 (SF-12). A convenience sample of 211 patients
      with heart failure completed baseline questionnaires via telephone interviews.
      Follow-up interviews were conducted at four, eight and 26 weeks. A total of 165
      patients (78 per cent) completed the study, while 11 patients (5 per cent) died
      during the course of the research project. Overall, the results indicated that
      patients had a lowto-moderate health-related quality of life.

PMID- 27707317
TI  - An exploration of the contribution of the community nurse to rehabilitation.
AB  - In all the recent discussion of the need to improve the co-ordination and
      delivery of rehabilitation services for older people, community nurses often
      feel, with some justice, that their potential contribution has been overlooked.
      So this paper is timely in its focus on an area of nursing practice that is ripe
      for development. The researchers used a grounded theory approach to the analysis
      of data generated by focus group discussions and individual interviews with
      district nurses. The results indicated that community nurses described their
      practice as 'holistic' in combining both health and social aspects. They were
      involved in making assessments, referrals, teaching and educating, and providing
      technical care. Despite this major contribution, many of the nurses felt that
      their role in rehabilitation was not clearly defined or accorded sufficient
      recognition by other service providers.

PMID- 27707321
TI  - Explorations in Dementia Michael Bender Explorations in Dementia Jessica Kingsley
      Publishers 443pp L19.95 1 843100401 1843100401 [Formula: see text].
AB  - This is a dangerous and deeply flawed book in which the author 'roasts' an array
      of old chestnuts. The premise is that there is a 'standard paradigm' of dementia
      and that this standard paradigm is wrong. The standard paradigm attributes
      dementia to a series of underlying pathologies and says that dementia is
      progressive and debilitating.

PMID- 27707324
TI  - Ethical approaches to physical interventions: responding to challenging behaviour
      in people with intellectual disabilities David Allen Ethical approaches to
      physical interventions: responding to challenging behaviour in people with
      intellectual disabilities BILD Publications (The Foundation for People with
      Learning Disabilities) L18 + 10 per cent p&p 190408 2386 1904082386.
AB  - This book, based on contributions from leading academics and practitioners in the
      UK and USA, presents an overview of key developments and current best practice in
      this field. The text includes analysis of current policies and practices, an
      examination of physical interventions and abusive practice, and a discussion of
      objectives for the immediate future.

PMID- 27707325
TI  - Down's syndrome and dementia resource pack: for carers and support staff Karen
      Dodd Down's syndrome and dementia resource pack: for carers and support staff ,
      Vicky Turk and Michelle Christmas BILD Publications (The Foundation for People
      with Learning Disabilities) L25 + 10 per cent p&p 1904082378 1904082378.
AB  - A resource pack for family carers, staff and professionals on how to care more
      effectively for people with Down's syndrome and dementia. The pack focuses on
      practical day-to-day issues including: supporting a person in maintaining skills
      and independence for as long as possible; treating treatable conditions;
      understanding and responding to changes in behaviour in dementia; providing
      emotional reassurance for carers; improving carers' confidence; identifying local
      resources; and being open to problems, with tips on how to cope.

PMID- 27707326
TI  - Show me the way to go home of millstones and milestones.
AB  - In April 2003 the Community Care (Delayed Discharges etc) Bill received royal
      assent and became an official act of parliament. Under this piece of legislation,
      social services departments unable to provide appropriate community care services
      for someone about to come out of hospital within set timescales will be 'fined'
      by the hospital concerned (a system known as reimbursement).

PMID- 27707329
TI  - ?
AB  - A nurse has been inundated with orders from NHS suppliers after inventing a
      plastic basket that can be attached to walking frames. The basket is big enough
      for users to store essential items and comes with a dinner tray and hot drinks
      holder.

PMID- 27707328
TI  - Services for older people fall short, says government watchdog.
AB  - Services for older people are often lacking in privacy and dignity, according to
      a government watchdog's analysis of 250 reports on NHS organisations.

PMID- 27707330
TI  - National forum launched to improve lives of bme elders.
AB  - Leaders of the UK's black and minority ethnic (BME) communities have joined Age
      Concern England to launch a national forum aimed at improving the lives of BME
      elders all over the country. Minority ethnic groups are the fastest ageing groups
      within the population and by 2030 it is estimated that the minority ethnic elder
      population will have increased tenfold to 1.7 million. Gordon Lishman, director
      general of Age Concern England, said: 'The forum will play a crucial role in
      enabling real and lasting change to policy and existing services, making a
      difference to the lives of older people in our increasingly diverse ageing
      population.' Pictured with Mr Lishman (centre) at the forum's launch are pensions
      minister Maria Eagle, and forum chair Len Shillingford (see Older Voices, pages
      10-13 ).

PMID- 27707331
TI  - NHS 'turning the corner' on orthopaedic surgery.
AB  - Reforms have been announced by the Department of Health in England to cut the
      estimated quarter of a million patients, mainly older people, who are currently
      waiting for hip replacements and other orthopaedic surgery.

PMID- 27707332
TI  - ?
AB  - The issue of how to assess the degree of insight possessed by people suffering
      from dementia is a key one for clinicians, carers and researchers. In this
      thought-provoking paper, 32 subjects with mild to moderate dementia were
      recruited from attenders at two day hospitals. Subjects and their carers
      completed range of assessment tools, and then took part in semi-structured
      interviews. Themes identified in the interviews included frustration, distress
      and anger, discontent, unconcern, a normalizing response, worry and anxiety,
      defensiveness, explicit denial, and priority given to other problems. The
      researchers conclude that insight is a complex, multi-dimensional and value-laden
      concept.

PMID- 27707333
TI  - Home owners' fury over CRB checks.
AB  - The government is trying deliberately to make care-home owners pay more to
      complete vital paperwork, the National Care Homes Association (NCHA) has said.

PMID- 27707335
TI  - John Adams scans a range of journals and highlights their relevance for nurses
      who work with older people.
AB  - There is increasing recognition that for many older people, a fall causing a hip
      fracture can start a process of increasing dependency and reduced quality of
      life. However, this is not an inevitable outcome and researchers are keen to
      identify factors which may influence prognosis. In this American study, data were
      obtained from 23 women (age range 65 - 95 years) who had sustained a hip fracture
      within the previous four years. A range of instruments were completed by a
      research nurse, including measures of independence in activities of daily living,
      and osteoporosis risk. Eighteen of the women were able to obtain maximum scores
      for independence in living activities after the fracture was treated. The results
      provided the positive message that older women who were living independently
      before their fall can expect a high level of recovery from this traumatic event.

PMID- 27707337
TI  - The association between knee temperature and pain in elders with osteoarthritis
      of the knee: a pilot study.
AB  - This small-scale study set out to test the hypothesis that there was an
      association between skin surface temperature and perceived pain in
      osteoarthritis. If such an association could be demonstrated in cognitively
      intact older people, the authors argued that it could form a useful aid to
      assessment for those who were cognitively impaired. Unfortunately, no such
      significant relationship was found. The authors suggest that environmental
      influences may outweigh the effects of inflammation of the knee joint in
      influencing skin temperature. They conclude by suggesting that the study should
      be repeated with a larger sample who had radiographic evidence to establish the
      extent of their osteoarthritis.

PMID- 27707339
TI  - Website watch.
AB  - Age Exchange If you have read the Older Voices feature on black and minority
      ethnic groups in this issue of Nursing Older People, you may have noted a list
      provided by the King's Fund library detailing recent books, articles and websites
      categorised under 'ethnic elders'. One of the websites listed is this one.
      www.age-exchange.org.uk.

PMID- 27707338
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27707340
TI  - New health writers' award.
AB  - A new award to recognise the contribution journalists and writers make to older
      people's health issues is being launched by Research into Ageing, a special trust
      within Help the Aged.

PMID- 27707341
TI  - Breaking new ground.
AB  - Some hospitals are starting discharge planning on admission, identifying problems
      and potential obstacles to the patient's discharge. Nationally, many trusts have
      introduced strategies to address these issues, linking to modernisation projects
      and the National Service Framework for Older People (NSF).

PMID- 27707345
TI  - Army life.
AB  - Describe the job you do now and your previous work with the Salvation Army I am
      part of the new compliance and monitoring unit (CMU) set up by the Salvation Army
      (SA) to ensure that all their 96 social care centres meet the standard set by the
      care commissions, social care councils and supporting people legislation. I cover
      the whole of Scotland, northern England and Yorkshire, travelling from Inverness
      to Sheffield to inspect 27 centres.

PMID- 27707346
TI  - Letters.
AB  - I was delighted to read your editorial highlighting good care and would like to
      add my own example. My grandmother-in-law is 93, has lost visual and hearing
      functioning completely and lives in an old age care home where the nurses, social
      workers and other helpers are committed to providing quality of care in a 'family
      visible' way.

PMID- 27707347
TI  - Making the most of research funding opportunities.
AB  - All researchers want more resources for their chosen subject, both to satisfy
      their personal curiosity and to find or examine something new and potentially
      valuable for their profession. Given that certain restraints, such as the number
      of hours in a day, are outside their control, individuals seek to find more time
      in their working life for research, and/or enhance the research facilities and
      environment in which they work. Inevitably these rely on funding, often sought
      from organisations or agencies other than the researcher's employer.

PMID- 27707350
TI  - Understanding research for nursing students Peter Ellis Understanding research
      for nursing students Learning Matters 144 Second edition L15 9781844453689
      1844453685 [Formula: see text].
AB  - This book does exactly what it says it will in that it could be a useful tool for
      helping nursing students to gain a deeper understanding of the research.

PMID- 27707348
TI  - Ethical decision making in social research: a practical guide (2009) Ron Iphofen
      Ethical decision making in social research: a practical guide (2009) Palgrave
      Macmillan 240 L52 9780230210356 023021035X [Formula: see text].
AB  - The author of this book describes it as a guide to thinking through the problems
      of conducting ethical research in the social sciences. As such it is intended to
      be of practical help to social researchers in resolving ethical issues that arise
      from undertaking research involving human subjects. Although it is written with
      social scientists in mind, much of the content is relevant to nurses undertaking
      research within the health service.

PMID- 27707351
TI  - Research methods for clinical therapists: applied project design and analysis
      Carolyn M Hicks Research methods for clinical therapists: applied project design
      and analysis Churchill LIvingstone 352 Fifth edition L22.99 9780043074301
      [Formula: see text].
AB  - Many who attend critical appraisal courses are keen to get under the skin of a
      research project. Just as stripping down a car engine offers insights into their
      design, appraising a published study helps to discover the key features of a
      particular research design.

PMID- 27707352
TI  - Effective people: leadership and organisation development in health care (Second
      edition) Stephen Prosser Effective people: leadership and organisation
      development in health care (Second edition) Radcliffe 320 L29.99 9781846193910
      846193915 [Formula: see text].
AB  - This is the second edition of the text and you will be at no disadvantage if you
      have not read the first. The preface to the book sets the scene clearly for, and
      identifies, how the book will progress.

PMID- 27707353
TI  - Glutathione-dependent micelles based on carboxymethyl chitosan for delivery of
      doxorubicin.
AB  - Novel glutathione (GSH)-dependent micelles based on carboxymethyl chitosan (CMCS)
      were developed for triggered intracellular release of doxorubicin (DOX). DOX-33'
      Dithiobis (N-hydroxysuccinimidyl propionate)-CMCS (DOX-DSP-CMCS) prodrugs were
      synthesized. DOX was attached to the amino group on CMCS via disulfide bonds and
      drug-loaded micelles were formed by self-assembly. The micelles formed core-shell
      structure with CMCS and DOX as the shell and core, respectively, in aqueous
      media. The structure of the prodrugs was confirmed by IR and proton nuclear
      magnetic resonance (1H NMR) spectroscopy. The drug-loading capacity determined by
      UV spectrophotometry was 4.96% and the critical micelle concentration of polymer
      prodrugs determined by pyrene fluorescence was 0.089 mg/mL. Micelles were
      spherical and the mean size of the nanoparticles was 174 nm, with a narrow
      polydispersity index of 0.106. Moreover, in vitro drug release experiments showed
      that the micelles were highly GSH-sensitive owing to the reductively degradable
      disulfide bonds. Cell counting kit (CCK-8) assays revealed that DOX-DSP-CMCS
      micelles exhibited effective cytotoxicity against HeLa cells. Moreover, confocal
      laser scanning microscopy (CLSM) demonstrated that DOX-DSP-CMCS micelles could
      efficiently deliver and release DOX in the cancer cells. In conclusion, the DOX
      DSP-CMCS nanosystem is a promising drug delivery vehicle for cancer therapy.

PMID- 27707354
TI  - Cognitive screening in Multiple Sclerosis: the Five-Point Test as a substitute
      for the PASAT in measuring executive function.
AB  - OBJECTIVE: The Paced Auditory Serial Addition Test (PASAT) is frequently employed
      to measure executive functions in patients with Multiple Sclerosis (MS). In the
      past, the PASAT has often been criticized because of its stressful and demanding
      requirements. Continuous utilization might also reduce its validity. The Five
      Point Test (FPT) by Regard, Strauss, and Knapp ((1982) Children's production on
      verbal and non-verbal fluency tasks. Perceptual and Motor Skills, 55, 839-844.)
      is a short test of figural fluency which might serve as a substitute. METHOD: 116
      patients diagnosed with MS were tested with a short version of the Brief
      Repeatable Battery (BRB) by Rao and the Cognitive Function Study Group of the
      National Multiple Sclerosis Society including the PASAT, as well as the FPT. A
      factor analysis was computed and the frequency of cognitive impairment was
      calculated for both the original short version of the BRB and the alternative
      version (involving the FPT). RESULTS: In the factor analysis, PASAT and FPT
      loaded highest on the same factor (two factors were extracted). The estimation of
      the frequency of cognitive impairment showed that replacing the PASAT with the
      FPT did not considerably alter the proportion of patients identified as
      cognitively impaired. CONCLUSIONS: The FPT proved to be a viable alternative to
      the PASAT in this study. It may be recommended as a possible replacement in
      neuropsychological screening of MS-patients with the advantage of avoiding the
      indicated limitations of the PASAT.

PMID- 27707357
TI  - Intensive Clinical Studies.

PMID- 27707355
TI  - Validation and application of a liquid chromatography-tandem mass spectrometry
      based method for the assessment of the co-occurrence of mycotoxins in maize
      silages from dairy farms in NW Spain.
AB  - The first objective of this study was the validation of an efficient multi
      analyte method for the simultaneous detection and quantification of mycotoxins in
      maize silage, by reverse-phase liquid chromatography coupled with electrospray
      ionisation triple quadrupole mass spectrometry (LC-HESI-MS/MS). A simple
      liquid/solid extraction was performed either with clean-up on Mycospin 400
      columns or without any clean-up. Almost all the target mycotoxins showed highly
      suppressed signals in the presence of a matrix, emphasising the need to
      quantitate mycotoxins by means of matrix-matched calibrations. An alternative
      validation method based on ISO 11843 and on a single factor balanced design was
      implemented. The achieved average recoveries from spiked samples at three levels
      ranged from 60% to 122% with relative standard deviations (rsd) below 11%. Limits
      of Detection (LODs) and Limits of Quantification (LOQs) were between 0.02-17.1 ug
      kg-1 and 0.06-57 ug kg-1. The calculated repeatability and within-lab
      reproducibility ranged from 5.2 to 23.2% and from 7.2 to 23.9%, respectively.
      Finally, the decision limit and detection capacity, CCalpha and CCbeta, were
      calculated for all mycotoxins having regulated/recommended contents in feed. The
      validated method was applied to 148 samples collected over two years in 19 dairy
      farms from Galicia (NW Spain). Of the analysed samples, 62% contained at least
      one mycotoxin. Zearalenone (ZEA), deoxynivalenol (DON), fumonisins B1 and B2,
      roquefortine C, alpha-zearalenol, beta-zearalenol, enniatins B and B1, andrastin
      A, marcfortine A, verruculogen and mycophenolic acid were quantified, the highest
      average detection frequency being for enniatin B (51%). DON, mycophenolic acid
      and ZEA plus metabolites (alpha-zearalenol, beta-zearalenol) were the most
      abundant mycotoxins.

PMID- 27707362
TI  - Longitudinal Research on Risk and Prevention in Mental Health.

PMID- 27707363
TI  - Creatine Kinase and Enolase: Intracellular Enzymes Serving as Markers of Central
      Nervous System Damage in Neuropsychiatric Disorders.

PMID- 27707368
TI  - Analysing qualitative data using a software package.
AB  - Since the 1970s, interest in qualitative approaches to research among nurses and
      midwives has increased ( 1 ). As clinicians become more aware of the potential
      benefits of interpretive methodologies and as more of them engage in further and
      higher education, the need to be able to analyse qualitative research data
      efficiently increases.

PMID- 27707365
TI  - A survey on the potential relationships between TMD, possible sleep bruxism,
      unilateral chewing, and occlusal factors in Turkish university students.
AB  - OBJECTIVE: To evaluate whether there is a relationship between possible sleep
      bruxism (PSB), temporomandibular disorders (TMD), unilateral chewing (UC), and
      occlusal factors in university students recruited from Cumhuriyet University in
      Turkey. METHODS: For this cross-sectional survey, 519 (223 males, mean age 21.57
      +/- 2.3 years, 296 females, mean age 21.02 +/- 2 years) university students who
      admitted to the Department of Oral and Maxillofacial Radiology of the Faculty of
      Dentistry, Cumhuriyet University for dental care between 2012 and 2014 were
      selected randomly. Students were asked to complete a questionnaire form including
      questions about TMD, PSB and UC. Presence and direction of malocclusion were
      recorded during clinical examination. Chi-square test was used for statistical
      analysis. RESULTS: It was found that 96.6% of the students with PSB had TMD (p <
      0.05). The prevalence of severe TMD was high among students with PSB. There was a
      significant association between UC, PSB and TMD (p < 0.05). No statistically
      significant association was found between occlusal factors and PSB and TMD (p >
      0.05). CONCLUSION: Sleep bruxism, which heavily depends on self-report, is
      significantly associated with TMD. Unilateral chewing seems to be a common factor
      for development of SB and TMD. However, further studies are needed to corroborate
      this finding. Additionally, this study supports the hypothesis that occlusal
      factors are not related to self-reported sleep bruxism.

PMID- 27707369
TI  - A multi-stage approach to the coding of data from open-ended questions.
AB  - One of the criticisms of qualitative research is that the processes and
      procedures of data analysis tire often not made explicit ( 1 ). This criticism is
      particularly pertinent to the analysis of open-ended questions. This paper
      outlines an approach to analysing open-ended questions using content analysis,
      making explicit the processes and procedures involved. The paper will also
      describe how the challenge of ensuring rigour and maintaining the diversity and
      subtlety of responses, which can easily be lost when attempting to quantify
      qualitative data, can be overcome.

PMID- 27707370
TI  - Writing and submitting abstracts for conference presentation.
AB  - Over the last 25 years it has frequently been said or written that nursing must
      be a research-based profession and there is now considerable pressure on staff in
      the NHS to achieve research-based practice. But this means that nurses must first
      know about relevant research findings. Hunt's comment ( 1 ) that nurses do not
      know about research findings has been quoted frequently, much nursing research is
      not published ( 2 ), and at least one study indicated that in the 1990s only a
      minority of nurses read journals regularly ( 3 ). It is possible that even those
      who do read nursing journals may not read research articles, judging by the
      journals cited by respondents in the study and their negative comments about
      reading research.

PMID- 27707372
TI  - The process and importance of systematic reviews.
AB  - The current emphasis within the NHS on clinical effectiveness involves the need
      to ensure that practice is based on knowledge derived from research rather than
      on strongly held tradition or personal experience. However, busy practitioners
      find it increasingly difficult to keep abreast of all available research. This is
      hardly surprising when one considers that there are over 20,000 biomedical
      journals which contain over two million articles each year ( 1 ). These articles
      vary greatly in quality and often are not well indexed. Practitioners involved in
      patient care rarely have the time, resources and skills to gather together and
      critically appraise relevant research in an effort to inform their practice.
      However, one way of pulling together unmanageable amounts of research is through
      a systematic review ( 2 ): 'A systematic- review is the process of systematically
      locating, appraising and synthesising evidence from scientific studies in order
      to obtain a reliable overview.'

PMID- 27707373
TI  - Using meta-analysis to summarise evidence within systematic reviews.
AB  - Systematic review and meta-analysis are two methods, used to summarise scientific
      evidence in order to inform further research and policy, that are being used with
      increasing frequency. It is important, therefore, that nurses and other health
      professionals understand how a systematic review and meta-analysis are carried
      out, and something of the relationship between the two methods. Systematic
      review, also known as overview, and meta-analysis can provide concise information
      for providers, purchasers and patients. However, it is helpful to appreciate when
      it may, or may not, be appropriate to perform them, as they are often a
      justification for wide ranging claims made about effectiveness of healthcare
      interventions.

PMID- 27707374
TI  - Editorial.
AB  - Developing an evidence or research-based culture in nursing is a complex issue.
      Hicks, in her paper 'Nurse researcher: a study of a contradiction in terms? '( 1
      ), suggested: 'The qualities attributed to a good nurse are dissonant with those
      attributed to a good researcher and, in this way, the mutual incompatibility of
      each role's requirements may serve as an obstacle to the development of research
      with nursing.' In other words, good nurses do not make good researchers or vice
      versa.

PMID- 27707375
TI  - Dissemination and implementation: the wider picture.
AB  - The current trend towards the adoption of evidence or knowledge- based practice
      in nursing provides the opportunity to reassess what has historically been
      referred to as the 'theory-practice gap'. I believe that the current way in which
      research findings are disseminated is the most important contributing factor to
      this gap. This paper will examine some of the issues and, where available, the
      evidence related to the dissemination of research findings in nursing. This paper
      addresses three components of dissemination.

PMID- 27707376
TI  - Publishing original research: principles and practice.
AB  - Experience has taught me that there is definitely a knack to getting your written
      research published, although, in this the era of 'evidence- based practice',
      empirical research to substantiate this claim is sadly lacking. Just as there are
      good practitioners, good teachers and good researchers, there are good writers.
      However, it is not always the good writers, and definitely not always the good
      researchers, who manage to ensure their work is published. It is the experienced
      or canny writers whose work proliferates, those who can turn their hand to many
      subjects, or mould any set of information into something that is worthy of
      publication.

PMID- 27707377
TI  - Is nursing research detrimental to nursing education and practice?
AB  - This paper expresses some personal concerns regarding the relationship between
      nursing education and research, and between nursing practice and research. My aim
      is to challenge, and to encourage in-depth consideration of, the implications of
      terms such as 'research-based practice', and more particularly, the concept that
      'nursing should be a research-based profession'.

PMID- 27707378
TI  - The Etiology of Borderline Personality Disorder.

PMID- 27707380
TI  - Commentary on Clay and Weingarten.

PMID- 27707382
TI  - Introduction.

PMID- 27707381
TI  - Commentary on Clay and Weingarten.

PMID- 27707383
TI  - The case for interactive interviewing.
AB  - It is reported in the Penguin Book of Interviews ( 1 ) that Marlon Brando
      recalled an interview with Truman Capote as follows: 'The little bastard spent
      half the night telling me all his problems, I figured the least I could do was
      tell him a few of mine.' In sharing experiences with his interviewee, Capote had
      managed to extract information he would otherwise not have gained.

PMID- 27707384
TI  - Editorial.
AB  - Brink and Wood have recently defined the inescapable logic of interviewing in
      nursing research. 'When your objective is to find out what people believe or
      think', they write, 'the easiest and most effective method is to ask questions
      directly of the person' ( 1 ).

PMID- 27707385
TI  - Personal experience of conducting unstructured interviews.
AB  - I am at present conducting a PhD study into the effects supernumerary status and
      mentorship on student nurses. The purpose of this article is to share some of my
      experiences, and suggest some pointers for planning and conducting unstructured
      interviews.

PMID- 27707386
TI  - Analysing data using a wordprocessor.
AB  - The analysis of data obtained from semi-structured and unstructured interviews is
      an essential part of many qualitative research studies. While a number of
      research texts offer suggestions as to how such text may be content analysed, few
      are explicit on this issue ( 1 , 2 ). The aim of this article is to offer a
      detailed account of one way of content analysing interview transcripts using a
      wordprocessor.

PMID- 27707387
TI  - The Strategy for Research in Nursing in England: Initial impactIn May 1993, the
      Department of Health published The Report of the Taskforce on the Strategy for
      Research in Nursing, Midwifery and Health Visiting ( 1 ). The Taskforce had been
      appointed to consider the scope and objectives of research in England and the
      interfaces with other areas of health services research. Susan Read reports on
      its progress.
AB  - Researchers have often been criticised for their lack of responsibility for
      disseminating or implementing their findings ( 2 - 4 ). People speak of volumes
      of research gathering dust on forgotten shelves, and research reports being
      incomprehensible to the ordinary reader. Researchers too have sometimes
      criticised sponsoring bodies for taking no notice of their recommendations.

PMID- 27707389
TI  - The structured interview.
AB  - Structured interviewing is about uniformity, and is inextricably bound with the
      use of interview schedules. Some guidance on constructing schedules is therefore
      included in this article.

PMID- 27707390
TI  - Unstructured and semi-structured interviewing.
AB  - At first glance, the idea of collecting data through some kind of interviewing
      can seem an attractively easy one; it is just talking to people, asking questions
      and recording the answers. The would-be researcher quickly discovers, however,
      that interviewing can be a complex and daunting undertaking.

PMID- 27707388
TI  - Analysing data using grounded theory.
AB  - Grounded theory is a systematic research approach for the collection and analysis
      of qualitative data. The aim of the grounded theory approach is to generate an
      explanatory theory from the data being analysed, rather than trying to 'fit' the
      data into an existing theoretical framework ( 1 , 2 ).

PMID- 27707391
TI  - Nursing education and the Research Assessment Exercises.
AB  - Prior to 1989, the funding of British universities was the responsibility of the
      University Grants Committee (UGC). The UGC's traditional role was to represent
      the universities to government, and to act as a buffer between the two, the aim
      being to enable the universities to be independent of central (political) control
      ( 1 ).

PMID- 27707392
TI  - Analysing data: alternative methods.
AB  - It is widely appreciated that research is a practical as well as an intellectual
      activity. The essence of communicating the research process effectively to others
      depends largely upon the researcher's ability to convey clearly not only
      intellectual rigour, but also the stages through which information was collected
      and interpreted.

PMID- 27707394
TI  - Varieties of research interviews.
AB  - Interviewing can claim to be the most widely used method of research. It is
      therefore no surprise that interviewing takes many forms. The types of interview
      are usually differentiated by their degree of structure. Structured interviews In
      'structured' (or 'standardised') interviews, the wording of questions and their
      sequence is the same from one interview to another. The piece of paper the
      interviewer holds is called the 'interview schedule'.

PMID- 27707396
TI  - Neurological Trauma and Family Functioning.

PMID- 27707395
TI  - Transverse myelitis-like presentation of methanol intoxication: A case report and
      review of the literature.
AB  - CONTEXT: Methanol is the simplest member of alcohol family. However, it is an
      extremely toxic substance to humans upon exposure with severe and detrimental
      effects that range from visual loss to death. Spinal cord involvement in methanol
      intoxication is a rare occurrence. FINDINGS: In this article, we are reporting a
      case of methanol intoxication with extensive spinal cord involvement possibly due
      to necrosis. A literature review yielded only two cases of spinal cord
      involvement due to methanol intoxication. Our article is the first to discuss the
      spinal cord involvement specifically including interesting neuroimaging features.
      CONCLUSION/CLINICAL RELEVANCE: We recommend performing MRI of the cervicothoracic
      spine in every methanol intoxication case to exclude both asymptomatic and
      symptomatic cases of spinal cord involvement.

PMID- 27707397
TI  - Social Interaction and Symptom Sequences.

PMID- 27707398
TI  - Intensive Clinical and Subjective Studies.

PMID- 27707399
TI  - Family Images of Hospitalized Adolescents.

PMID- 27707400
TI  - Normal and Developmental Aspects of Masochism.

PMID- 27707401
TI  - Sudden Infant and Child Death as a Cultural Phenomenon.

PMID- 27707402
TI  - Age Differences in the Personality Characteristics of Suicide Completers.

PMID- 27707404
TI  - Writing your thesis Paul Oliver Writing your thesis Publisher: Sage No. of pages:
      208 L16.99 0761942998 0761942998 [Formula: see text].
AB  - So you need to write a thesis and want some succinct, practical guidance. You
      don't want to plough through hundreds of pages or follow up a list of references
      to other material. Both of these activities use up your precious study time and
      divert your attention from the subject material of the thesis.

PMID- 27707403
TI  - Leading and co-ordinating a multi-nurse researcher project.
AB  - Leading and co-ordinating a research project is a complex undertaking involving
      management of people, processes, budget and material resources. The task is even
      more complex when there are nine nurse researchers collecting and analysing data
      in the midst of their practice. In this paper, Theresa Mitchell and Steve Jones
      describe the experiences of the project lead and co-ordinator responsible for
      planning and managing such a project in the Oncology Centre in Gloucestershire,
      UK. Using examples from the project, the authors share some of the potential
      problems encountered during research activities, and propose strategies and
      remedies to address them.

PMID- 27707405
TI  - Using social theory Using social theory Michael Pryke et al Sage 196 L19.99
      0761943773 0761943773 [Formula: see text].
AB  - A book concerning social theory that is a core text for an Open University module
      about 'Human geography, philosophy and social theory' may not be a text to which
      nurse researchers are immediately drawn. However, this publication is worth a
      closer look.

PMID- 27707408
TI  - Making the most of time.
AB  - Undertaking an MPhil or PhD requires the student to develop many different
      skills, including the all important skill of time management ( Crofts 2002 ). At
      first glance, the prospect of spending three years (or the part-time equivalent)
      studying a single topic of interest might seem like an inordinate amount of time;
      you might even consider it as something of a luxury. However, you are probably
      familiar with the saying tempus fugit; 'time flies'. In other words, the time
      which has been set aside for your MPhil or PhD will soon pass. It is important
      from an early stage that you get to grips with the 'time issue'; that you learn
      to manage your time effectively.

PMID- 27707409
TI  - Discourse analysis and social constructionism.
AB  - Discourse analysis (DA) is underpinned by a social constructionist orientation to
      knowledge. Social constructionism rests on the philosophical assumptions that
      multiple versions of the world are legitimate; that texts are open to multiple
      readings; and that language is non-representational. As social constructionism is
      relativistic, the status of 'evidence' generated by DA is questionable from more
      traditional research perspectives. On a common-sense level, people obviously
      construct meaning in relation to their lives. Thus, DA can help us to examine
      constructions of meaning in relation to nursing care. Equally, the discourse
      analyst constructs one possible meaning in relation to a phenomenon that may
      compete with other versions. Multiplicity does not necessarily entail anarchy,
      and competing versions prevent authoritarianism and loss of freedom. However,
      judgements have to be made about competing versions, for example, by assessing
      the level of 'facticity', or referring to the ethics embedded in the cultural
      context. In this paper, Bob White discusses DA as a form of qualitative research
      that offers promise for nursing research. Subsequent papers will examine the
      methodology and methods of DA and its application to nursing research.

PMID- 27707411
TI  - Networking works.
AB  - The importance of networking in bridging the theory-practice gap cannot be
      underestimated. Developing links with colleagues within your field can offer many
      opportunities to disseminate good practice and share ideas for the improvement of
      health care. There are many potential networking opportunities, for example, the
      RCN is hosting its annual international nursing conference in Belfast, Northern
      Ireland, UK, from March 8-11 2005. For further information, see:
      www.man.ac.uk/rcn/research2005/.

PMID- 27707410
TI  - Application of discourse analysis to nursing inquiry.
AB  - Discourse analysis (DA) has frequently been misapplied within nursing research,
      demonstrating a lack of understanding among some nurse researchers of
      theoretical/ methodological approaches within DA. To date, there are few specific
      nursing examples illustrating the application of DA, which presents a further
      obstacle for the new researcher. In this paper, Jim Campbell and Sheila Arnold
      outline a specific nursing example of DA research and describe the process of
      applying DA to nursing research via the personal experiences of the authors. Two
      different ways of 'coming to' a DA approach, will be described, one using a
      structured framework and the other a personal narrative.

PMID- 27707412
TI  - Discourse analysis.
AB  - First, a suggested definition of discourse: at its most general, discourse can be
      understood as any system of signs, whether spoken, written, or otherwise. I say
      'otherwise', because it is possible to 'read' town planning or architecture, for
      example, as systems that reflect and enact political values and practices. Some
      use the term a little more specifically; so, for example a phrase such as
      'medical discourse' implies an organised and more or less self-conscious system
      of concepts and language practice which reflects and is supported by an
      institutional base. Some while ago, Ian Parker set out certain characteristics of
      discourse and, importantly, questioned any notion of a simple distinction between
      discourse and 'reality' - something that can be comprehended outside of
      discourse.

PMID- 27707413
TI  - Researching 'race' and ethnicity Researching 'race' and ethnicity Yasmin
      Gunaratnam Sage 224 L18.99 0761972870 0761972870 [Formula: see text].
AB  - This book emerges at a critical time in developing research to aid understanding
      of the health needs of minority ethnic groups. The development of key initiatives
      in the health of minority ethnic groups is hampered by the lack of information
      about the ways in which issues of 'race', ethnicity and experiences impact on
      individuals and communities. Researchers working in nursing and health care have
      begun to research ethnicity and 'race' within a more politicised context which
      seeks to expose the impact of inequality within a 'race' and ethnicities based
      framework.

PMID- 27707414
TI  - Theoretical and methodological approaches in discourse analysis.
AB  - Discourse analysis (DA) embodies two main approaches: Foucauldian DA and radical
      social constructionist DA. Both are underpinned by social constructionism to a
      lesser or greater extent. Social constructionism has contested areas in relation
      to power, embodiment, and materialism, although Foucauldian DA does focus on the
      issue of power. Embodiment and materialism may be especially relevant for
      researchers of nursing where the physical body is prominent. However, the
      contested nature of social constructionism allows a fusion of theoretical and
      methodological approaches tailored to a specific research interest. In this
      paper, Chris Stevenson suggests a frame- work for working out and declaring the
      DA approach to be taken in relation to a research area, as well as to aid
      anticipating methodological critique. Method, validity, reliability and
      scholarship are discussed from within a discourse analytic frame of reference.

PMID- 27707415
TI  - The evidence for nursing interventions in the Cochrane Database of Systematic
      Reviews.
AB  - In this paper, Patriek Mistiaen, Else Poot, Sophie Hickox, and Cordula Wagner
      describe how they conducted a search of the Cochrane Database of Systematic
      Reviews in order to explore the evidence for nursing interventions. They identify
      the number of studies, the number of participants, and the conclusions of
      systematic reviews concerning nursing interventions. They conclude that the
      Cochrane Database of Systematic Reviews is a valuable source of evidence about
      nursing interventions, and can be used as a means of developing a research agenda
      in the case of inconclusive reviews.

PMID- 27707416
TI  - Upper trapezius fatigue in carpet weaving: the impact of a repetitive task cycle.
AB  - INTRODUCTION: Shoulder disorders are one of the most prevalent musculoskeletal
      disorders among carpet weavers. The most important cause of these disorders is
      muscle fatigue. The aim of the present study is to investigate the effect of
      carpet weaving characteristics on upper trapezius (UTr) muscle fatigue during a
      task cycle. METHOD: In this cross-sectional study, 9 women and 3 men
      participated. During an 80-min cycle of carpet weaving, a times-series model was
      applied to assess electromyography amplitude and frequency changes. RESULT:
      According to the joint analysis of electromyogram spectrum and amplitude method,
      the participants experienced 0% force decrease, 0.9% recovery, 18% force increase
      and 72% fatigue in the left UTr. Furthermore, the rates of force decrease,
      recovery, force increase and fatigue in the right UTr were 18%, 18%, 18% and 45%,
      respectively. Fatigue in the right and the left UTr was reported to be the
      dominant state during one carpet weaving task cycle. CONCLUSION: Task cycle
      appears to have a significant impact on UTr fatigue in participants, and UTr
      fatigue can be considered a serious risk factor in shoulder musculoskeletal
      disorders. Hence, further studies should focus on better workstations and work
      rest periods during various subtasks.

PMID- 27707417
TI  - [Universal Dutch guideline on 'Venous disease'].
AB  - - The Dutch guideline on 'Venous disease' comprises four parts: two revised
      guidelines ('Varicose veins' and 'Venous leg ulcer') and two new guidelines
      ('Deep venous disease' and 'Compression therapy').- These guidelines were drawn
      up by a working party made up of representatives from the Dutch Association of
      Surgeons, the Dutch Society of Vascular Surgery and the Dutch Society of
      Dermatology and Venereology.- We will discuss the most important parts of the
      guideline here.

PMID- 27707418
TI  - The role of chemokines and their receptors during protist parasite infections.
AB  - Protists are a diverse collection of eukaryotic organisms that account for a
      significant global infection burden. Often, the immune responses mounted against
      these parasites cause excessive inflammation and therefore pathology in the host.
      Elucidating the mechanisms of both protective and harmful immune responses is
      complex, and often relies of the use of animal models. In any immune response,
      leucocyte trafficking to the site of infection, or inflammation, is paramount,
      and this involves the production of chemokines, small chemotactic cytokines of
      approximately 8-10 kDa in size, which bind to specific chemokine receptors to
      induce leucocyte movement. Herein, the scientific literature investigating the
      role of chemokines in the propagation of immune responses against key protist
      infections will be reviewed, focussing on Plasmodium species, Toxoplasma gondii,
      Leishmania species and Cryptosporidium species. Interestingly, many studies find
      that chemokines can in fact, promote parasite survival in the host, by drawing in
      leucocytes for spread and further replication. Recent developments in drug
      targeting against chemokine receptors highlights the need for further
      understanding of the role played by these proteins and their receptors in many
      different diseases.

PMID- 27707419
TI  - Molecular characterization and detection of variants of Taenia multiceps in sheep
      in Turkey.
AB  - Taenia multiceps is a cestode (family Taeniidae) that in its adult stage lives in
      the small intestine of dogs and other canids. The metacestode, known as Coenurus
      cerebralis, is usually found in the central nervous system including brain and
      spinal card in sheep and other ruminants. The presence of cysts typically leads
      to neurological symptoms that in the majority of cases result in the death of the
      animal. Coenurosis could cause high losses in sheep farms because the disease
      commonly affects young animals. A total of 20 C. cerebralis isolates collected
      from naturally infected sheep in Mardin province of Turkey were characterized
      through the polymerase chain reaction and sequencing of a fragment of cytochrome
      c oxidase subunit 1 (CO1) gene. The results showed that the CO1 gene sequences
      were highly conserved in C. cerebralis isolates. Phylogenetic analysis based on
      partial CO1 gene sequences revealed that C. cerebralis isolates were composed of
      three different variants.

PMID- 27707420
TI  - Molecular characterization of 5S ribosomal RNA genes and transcripts in the
      protozoan parasite Leishmania major.
AB  - Eukaryotic 5S rRNA, synthesized by RNA polymerase III (Pol III), is an essential
      component of the large ribosomal subunit. Most organisms contain hundreds of 5S
      rRNA genes organized into tandem arrays. However, the genome of the protozoan
      parasite Leishmania major contains only 11 copies of the 5S rRNA gene, which are
      interspersed and associated with other Pol III-transcribed genes. Here we report
      that, in general, the number and order of the 5S rRNA genes is conserved between
      different species of Leishmania. While in most organisms 5S rRNA genes are
      normally associated with the nucleolus, combined fluorescent in situ
      hybridization and indirect immunofluorescence experiments showed that 5S rRNA
      genes are mainly located at the nuclear periphery in L. major. Similarly, the
      tandemly repeated 5S rRNA genes in Trypanosoma cruzi are dispersed throughout the
      nucleus. In contrast, 5S rRNA transcripts in L. major were localized within the
      nucleolus, and scattered throughout the cytoplasm, where mature ribosomes are
      located. Unlike other rRNA species, stable antisense RNA complementary to 5S rRNA
      is not detected in L. major.

PMID- 27707421
TI  - Narrow band imaging versus autofluorescence imaging for head and neck squamous
      cell carcinoma detection: a prospective study.
AB  - OBJECTIVES: This study aimed to compare the diagnostic effectiveness of narrow
      band imaging and autofluorescence imaging for malignant laryngopharyngeal
      tumours. METHODS: Between May 2010 and October 2010, 50 consecutive patients with
      suspected laryngopharyngeal tumour underwent endoscopic laryngopharynx
      examination. The morphological characteristics of laryngopharyngeal lesions were
      analysed using high performance endoscopic systems equipped with narrow band
      imaging and autofluorescence imaging modes. The diagnostic effectiveness of white
      light image, narrow band imaging and autofluorescence imaging endoscopy for
      benign and malignant laryngopharyngeal lesions was evaluated. RESULTS: Under
      narrow band imaging endoscopy, the superficial microvessels of squamous cell
      carcinomas appeared as dark brown spots or twisted cords. Under autofluorescence
      imaging endoscopy, malignant lesions appeared as bright purple. The sensitivity
      of malignant lesion diagnosis was not significantly different between narrow band
      imaging and autofluorescence imaging modes, but was better than for white light
      image endoscopy (chi2 = 12.676, p = 0.002). The diagnostic specificity was
      significantly better in narrow band imaging mode than in both autofluorescence
      imaging and white light imaging mode (chi2 = 8.333, p = 0.016). CONCLUSION:
      Narrow band imaging endoscopy is the best option for the diagnosis and
      differential diagnosis of laryngopharyngeal tumours.

PMID- 27707422
TI  - Current demand of paediatric otolaryngology input for children with Down's
      syndrome in a tertiary referral centre.
AB  - OBJECTIVE: This study aimed to evaluate the activity of paediatric otolaryngology
      services required for children with Down's syndrome in a tertiary referral
      centre. METHODS: A review of the paediatric otolaryngology input for children
      with Down's syndrome was performed; data were obtained from the coding department
      for a two-year period and compared with other surgical specialties. RESULTS:
      Between June 2011 and May 2013, 106 otolaryngology procedures were performed on
      children with Down's syndrome. This compared to 87 cardiac and 81 general
      paediatrics cases. The most common pathologies in children with Down's syndrome
      were obstructive sleep apnoea, otitis media, hearing loss and cardiac disease.
      The most common otolaryngology procedures performed were adenoidectomy,
      tonsillectomy, grommet insertion and bone-anchored hearing aid implant surgery.
      CONCLUSION: ENT manifestations of Down's syndrome are common. Greater provisions
      need to be made to streamline the otolaryngology services for children and
      improve transition of care to adult services.

PMID- 27707423
TI  - Impact of Ultraviolet Germicidal Irradiation for No-Touch Terminal Room
      Disinfection on Clostridium difficile Infection Incidence Among Hematology
      Oncology Patients.
AB  - OBJECTIVE To evaluate the impact of no-touch terminal room no-touch disinfection
      using ultraviolet wavelength C germicidal irradiation (UVGI) on C. difficile
      infection (CDI) rates on inpatient units with persistently high rates of CDI
      despite infection control measures. DESIGN Interrupted time-series analysis with
      a comparison arm. SETTING 3 adult hematology-oncology units in a large, tertiary
      care hospital. METHODS We conducted a 12-month prospective valuation of UVGI.
      Rooms of patients with CDI or on contact precautions were targeted for UVGI upon
      discharge using an electronic patient flow system. Incidence rates of healthcare
      onset CDI were compared for the baseline period (January 2013-December 2013) and
      intervention period (February 2014-January 2015) on study units and non-study
      units using a mixed-effects Poisson regression model with random effects for unit
      and time in months. RESULTS During a 52-week intervention period, UVGI was
      deployed for 542 of 2,569 of all patient discharges (21.1%) on the 3 study units.
      The CDI rate declined 25% on study units and increased 16% on non-study units
      during the intervention compared to the baseline period. We detected a
      significant association between UVGI and decrease in CDI incidence (incidence
      rate ratio [IRR], 0.49; 95% confidence interval [CI], 0.26-0.94; P=.03) on the
      study units but not on the non-study units. The impact of UVGI use on average
      room-cleaning time and turnaround time was negligible compared to the baseline
      period. CONCLUSIONS Targeted deployment of UVGI to rooms of high-risk patients at
      discharge resulted in a substantial reduction of CDI incidence without adversely
      impacting room turnaround. Infect Control Hosp Epidemiol 2016;1-6.

PMID- 27707424
TI  - Adenoidectomy can improve obstructive sleep apnoea in young children: systematic
      review and meta-analysis.
AB  - OBJECTIVE: To systematically search for studies reporting outcomes for
      adenoidectomy alone as a treatment for paediatric obstructive sleep apnoea and
      use the data to perform a meta-analysis. METHODS: Nine databases, including
      PubMed and Medline, were systematically searched through to 1 April 2016. The
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was
      followed. RESULTS: A total of 1032 articles were screened and 126 full texts were
      reviewed. Three paediatric studies (47 patients) reported outcomes. Overall,
      apnoea-hypopnoea index values decreased from 18.1 +/- 16.8 to 3.1 +/- 5.5 events
      per hour (28 patients). Random-effects modelling demonstrated a mean difference
      of -14.43 events per hour (I2 = 23 per cent (low inconsistency)). The apnoea
      hypopnoea index standardised mean difference was -1.14 (large magnitude of
      effect). The largest reduction in apnoea-hypopnoea index was observed in children
      aged less than 12 months (reduction of 56.6-94.9 per cent). Lowest oxygen
      saturation values improved from 80.0 +/- 9.5 to 85.5 +/- 6.0 per cent (13
      children). CONCLUSION: Adenoidectomy alone has improved obstructive sleep apnoea
      in children, especially in those aged less than 12 months; however, given the low
      number of studies, isolated adenoidectomy remains an area for additional
      research.

PMID- 27707425
TI  - Can curcumin modulate allergic rhinitis in rats?
AB  - OBJECTIVES: This study aimed to explore the effects of curcumin on experimental
      allergic rhinitis in rats. METHODS: Twenty-eight male Wistar albino rats were
      randomly divided into four groups: a control group; a group in which allergic
      rhinitis was induced and no treatment given; a group in which allergic rhinitis
      was induced followed by treatment with azelastine hydrochloride on days 21-28;
      and a group in which allergic rhinitis was induced followed by treatment with
      curcumin on days 21-28. Allergy symptoms and histopathological features of the
      nasal mucosa were examined. RESULTS: The sneezing and nasal congestion scores
      were higher in the azelastine and curcumin treatment groups than in the control
      group. Histopathological examination showed focal goblet cell metaplasia on the
      epithelial surface in the azelastine group. In the curcumin group, there was a
      decrease in goblet cell metaplasia in the epithelium, decreased inflammatory cell
      infiltration and vascular proliferation in the lamina propria. CONCLUSION:
      Curcumin is an effective treatment for experimentally induced allergic rhinitis
      in rats.

PMID- 27707426
TI  - Summer time predation on the obligatory off-host stage of an invasive
      ectoparasite.
AB  - Predation can regulate populations and strongly affect invasion success of novel
      prey. The deer ked (Lipoptena cervi; Linnaeus 1758) is an invasive ectoparasite
      of cervids that spends a long period of its life cycle outside the host. Prior to
      this study, virtually nothing was known about natural summer time predation on
      the deer ked. We aimed to evaluate the magnitude of summer time predation on L.
      cervi pupae in different habitats and to identify potential predators. We
      conducted a set of field experiments, where we exposed L. cervi pupae to various
      ground-dwelling vertebrate and invertebrate predators. The loss of pupae was
      monitored for different predator guilds. Three habitats of the moose, the main
      host species, were studied: (1) moist heath forest; (2) dry, logged heath forest;
      and (3) moist meadow. The results indicate notable summer time predation on L.
      cervi pupae, and the pupal predation varied within and between habitats, being
      lowest in the meadow habitat. We found a positive correlation between pupal loss
      and abundance of the common lizard (Zootoca vivipara), harvestmen (Opiliones),
      ground spiders (Gnaphosidae) and Formicinae-ants. We conclude that summer time
      predation during the pupal phase can have a notable local importance for the L.
      cervi abundance.

PMID- 27707427
TI  - Verrucosispora sonchi sp. nov., a novel endophytic actinobacterium isolated from
      the leaves of common sowthistle (Sonchus oleraceus L.).
AB  - A novel actinobacterium, designated strain NEAU-QY3T, was isolated from the
      leaves of Sonchus oleraceus L. and examined using a polyphasic taxonomic
      approach. The organism formed single spores with smooth surface on substrate
      mycelia. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that
      the strain had a close association with the genus Verrucosispora and shared the
      highest sequence similarity with Verrucosispora qiuiae RtIII47T (99.17 %), an
      association that was supported by a bootstrap value of 94 % in the neighbour
      joining tree and also recovered with the maximum-likelihood algorithm. The strain
      also showed high 16S rRNA gene sequence similarities to Xiangella phaseoli NEAU
      J5T (98.78 %), Jishengella endophytica 202201T (98.51 %), Micromonospora eburnea
      LK2-10T (98.28 %), Verrucosispora lutea YIM 013T (98.23 %) and Salinispora
      pacifica CNR-114T (98.23 %). Furthermore, phylogenetic analysis based on the gyrB
      gene sequences supported the conclusion that strain NEAU-QY3T should be assigned
      to the genus Verrucosispora. However, the DNA-DNA hybridization relatedness
      values between strain NEAU-QY3T and V. qiuiae RtIII47T and V. lutea YIM 013T were
      below 70 %. With reference to phenotypic characteristics, phylogenetic data and
      DNA-DNA hybridization results, strain NEAU-QY3T was readily distinguished from
      its most closely related strains and classified as a new species, for which the
      name Verrucosispora sonchi sp. nov. is proposed. The type strain is NEAU-QY3T
      (=CGMCC 4.7312T=DSM 101530T).

PMID- 27707428
TI  - Metabolite profiling of Phycomyces blakesleeanus carotene mutants reveals global
      changes across intermediary metabolism.
AB  - The filamentous fungus Phycomyces blakesleeanus provides a renewable biosource of
      industrial high-value compounds such as carotenes, other isoprenoids (ubiquinone
      and sterols), organic acids and fatty acids. Several Phycomyces mutants involved
      in the formation of beta-carotene are available. For example, the carA mutants
      have a leaky mutation in the phytoene synthase and produce significantly lower
      amounts of carotenes, while the carB and carR mutants produce phytoene and
      lycopene, respectively, due to a null mutation in the genes encoding the phytoene
      dehydrogenase and lycopene cyclase, respectively. The carS mutants are mutated in
      the gene encoding the oxygenase responsible for the conversion of beta-carotene
      into apocarotenoids and, as a result, beta-carotene accumulates. In order to
      ascertain further the biochemical changes arising in these potential industrial
      strains, a metabolite profiling workflow was implemented for Phycomyces. GC-MS
      and ultra-performance liquid chromatography-photodiode array platforms enabled
      the identification of over 100 metabolites in 11 carA, carB, carR and carS mutant
      strains and their wild-type comparator. All mutant strains possessed decreased
      TCA cycle intermediates, galactose, alanine and ribitol, while dodecanol and
      valine showed a general increase. As predicted, other terpenoid levels were
      affected in the carB, carR and carS mutants but not in the carA mutants. The
      global changes across intermediary metabolism of the mutants suggest that complex
      metabolic networks exist between intermediary and secondary metabolism or that
      other mutations beyond the carotene pathway may exist in these mutants. These
      data show the utility of the methodology in metabolically phenotyping Phycomyces
      strains with potential industrial exploitation.

PMID- 27707429
TI  - Three novel species of coccoid green algae within the Watanabea clade
      (Trebouxiophyceae, Chlorophyta).
AB  - Coccoid green algae are extremely diverse despite their simple coccoid phenotype,
      a phenotype that may be the result of convergent evolution. In this study, we
      used a polyphasic approach combining molecular phylogenetic analyses, morphology
      and ultrastructure to investigate isolated coccoid strains from China, and our
      results reveal three new lineages of Trebouxiophyceae: the novel genus and
      species Mysteriochloris nanningensis gen. et sp. nov., and the two novel species
      Phyllosiphon coccidium sp. nov. and Desertella yichangensis sp. nov.
      (Trebouxiophyceae, Chlorophyta). We provide a detailed characterization of the
      novel microalgae which they are autosporic coccoid unicells and have parietal
      chloroplasts. In phylogenies based on 18S rDNA sequences and the chloroplast
      ribulose-bisphosphate carboxylase gene (rbcL), these three algae are nested
      within the Watanabea clade and are different from any known algae. M.
      nanningensis FACHB-1787 is not really close to any known algae within the
      Watanabea clade. Phyllosiphoncoccidium FACHB-2212 is within the Phyllosiphon
      lineages. D. yichangensis FACHB-1793 is closely related to Desertella californica
      and described as a representative of a novel species of the genus Desertella.

PMID- 27707430
TI  - Luteimonas padinae sp. nov., an epiphytic bacterium isolated from an intertidal
      macroalga.
AB  - A Gram-stain-negative, rod-shaped bacterium, forming yellow colonies and
      designated CDR SL 15T, was isolated from the surface of Padina sp., a brown
      macroalga, which grows in the Western coastal regions of the state of Goa, India.
      The 16S rRNA gene sequence phylogeny placed the strain in the genus Luteimonas
      and it showed closest sequence similarity to Luteimonas terricola BZ92rT (97.6 %)
      and <97.0 % to other species of the genus Luteimonas. Chemotaxonomic features,
      such as having iso-C15 : 0 and summed feature 9 (C16 : 0 10-methyl/iso-C17 :
      1omega9c) as the major fatty acids and Q-8 as the only ubiquinone further
      supported its placement within this genus. There were some critical differences
      in phenotypic properties between Luteimonas padinae sp. nov. CDR SL 15T and L.
      terricola DSM 22344T i.e. temperature range for growth and salinity range and
      optimum for growth (L. terricola is a psychrotolerant bacterium with a lower
      optimum temperature for growth), acid production and assimilation of substrates,
      enzyme activities and resistance to certain antibiotics. The DNA-DNA relatedness
      value of the novel strain with its closest phylogenetic relative was only 40 %,
      below the 70 % threshold value recommended for species delineation. All these
      characteristics are consistent with strain CDR SL 15T representing a novel
      species of the genus Luteimonas, for which the name Luteimonas padinae sp. nov.
      is proposed. The type strain is CDR SL 15T (=DSM 101536T=KCTC 52403T).

PMID- 27707431
TI  - Algoriphagus litorisediminis sp. nov., isolated from a tidal flat.
AB  - A Gram-stain-negative, non-flagellated, non-gliding, aerobic and rod-shaped
      bacterium, designated strain OITF-19T, was isolated from a tidal flat in Oido, an
      island of South Korea, and subjected to a polyphasic taxonomic study. Strain OITF
      19T grew optimally at 30  degrees C, at pH 7.0-8.0 and in the presence of 2.0 %
      (w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene
      sequences revealed that strain OITF-19T belonged to the genus Algoriphagus,
      clustering with the type strain of Algoriphagus namhaensis, with which it shared
      96.5 % sequence similarity. Strain OITF-19T exhibited the highest 16S rRNA gene
      sequence similarity to Algoriphagus chungangensis CAU 1002T (97.0 %) and of 92.0
      96.8 % to the type strains of other Algoriphagus species. Strain OITF-19T
      contained MK-7 as the predominant menaquinone and summed feature 3 (C16 :
      1omega7c and/or C16 : 1omega6c), iso-C15 : 0 and iso-C17 : 0 3-OH as the major
      fatty acids. The major polar lipids detected in strain OITF-19T were
      phosphatidylcholine, phosphatidylethanolamine and three unidentified lipids. The
      DNA G+C content of strain OITF-19T was 38.3 mol%. Mean DNA-DNA relatedness
      between strain OITF-19T and the type strain of A. chungangensis was 26 %.
      Differential phenotypic properties, together with its phylogenetic and genetic
      distinctiveness, revealed that strain OITF-19T is separated from recognized
      species of the genus Algoriphagus. On the basis of the data presented, strain
      OITF-19T is considered to represent a novel species of the genus Algoriphagus,
      for which the name Algoriphagus litorisediminis sp. nov. is proposed. The type
      strain is OITF-19T (=KCTC 52456T=NBRC 112418T).

PMID- 27707432
TI  - Redefining homonyms under Rule 51b (4) of the International Code of Nomenclature
      of Prokaryotes.
AB  - As currently formulated, Rule 51b (4) of the International Code of Nomenclature
      of Prokaryotes does not fully reflect the wording of Principle 2. It is therefore
      important that the wording of Rule 51b (4) is updated to reflect the intent of
      Principle 2.

PMID- 27707433
TI  - Nakamurella silvestris sp. nov., an actinobacterium isolated from alpine forest
      soil.
AB  - A Gram-stain-positive, non-motile, catalase-positive and cytochrome c oxidase
      negative bacterium, designated strain S20-107T, was isolated from alpine forest
      soil. Growth occurred at 0-30  degrees C, at pH 6-9 and in the presence of 0-3 %
      (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that
      strain S20-107T was related to the genus Nakamurella and had the highest 16S rRNA
      gene sequence similarity with Nakamurella flavida DS-52T (96.1 %). Strain S20
      107T showed <96.1% 16S rRNA gene sequence similarities to all other recognized
      members of the genus Nakamurella. The cell-wall peptidoglycan contained meso
      diaminopimelic acid. The major whole-cell sugars were glucose, galactose,
      mannose, arabinose, ribose and rhamnose. The strain contained MK-8(H4) as the
      predominant menaquinone and diphosphatidylglycerol, phosphatidylethanolamine and
      an unidentified aminophospholipid as the major polar lipids. The major cellular
      fatty acids were anteiso-C15 : 0, C16 : 0, summed feature 3 (C16 : 1omega6c
      and/or C16 : 1omega7c and/or iso-C15 : 0 2-OH) and iso-C16 : 0. The genomic DNA
      G+C content was 70.5 mol%. Combined data of phylogenetic, phenotypic and
      chemotaxonomic analyses demonstrated that strain S20-107T represents a novel
      species of the genus Nakamurella, for which the name Nakamurella silvestris sp.
      nov. is proposed. The type strain is S20-107T (=DSM 102309T=LMG 29427T).

PMID- 27707434
TI  - Identification and taxonomic characterization of Bordetella pseudohinzii sp. nov.
      isolated from laboratory-raised mice.
AB  - Bordetella hinzii is known to cause respiratory disease in poultry and has been
      associated with a variety of infections in immunocompromised humans. In addition,
      there are several reports of B. hinzii infections in laboratory-raised mice. Here
      we sequenced and analysed the complete genome sequences of multiple B. hinzii
      like isolates, obtained from vendor-supplied C57BL/6 mice in animal research
      facilities on different continents, and we determined their taxonomic
      relationship to other Bordetella species. The whole-genome based and 16S rRNA
      gene based phylogenies each identified two separate clades in B. hinzii, one was
      composed of strains isolated from poultry, humans and a rabbit whereas the other
      clade was restricted to isolates from mice. Distinctly different estimated DNA
      DNA hybridization values, average nucleotide identity scores, gene content,
      metabolic profiles and host specificity all provide compelling evidence for
      delineation of the two species, B. hinzii - from poultry, humans and rabbit - and
      Bordetella pseudohinzii sp. nov. type strain 8-296-03T (=NRRL B-59942T=NCTC
      13808T) that infect mice.

PMID- 27707435
TI  - Progression of Polysomnographic Abnormalities in Mucolipidosis II (I-Cell
      Disease).
AB  - ABSTRACT: Mucolipidosis II (Inclusion cell or I-cell disease) is an autosomal
      recessive lysosomal storage disorder clinically comparable to the
      mucopolysaccharidoses (MPS), characterized by progressive respiratory and
      neurologic deterioration. Sleep problems, especially obstructive sleep apnea
      (OSA) and disrupted sleep architecture, are observed in other lysosomal storage
      diseases but have not been described in mucolipidosis II. We report the
      progression of polysomnographic abnormalities in a child with mucolipidosis II,
      demonstrated by worsening sleep-related hypoventilation, OSA, and sleep state
      fragmentation despite advancing PAP therapy. Background slowing and reduction in
      spindle activity on limited EEG may reflect progressive CNS disease affecting
      thalamic neurons.

PMID- 27707436
TI  - Treatment of OSA with CPAP Is Associated with Improvement in PTSD Symptoms among
      Veterans.
AB  - STUDY OBJECTIVES: Posttraumatic stress disorder (PTSD) is common among veterans
      of the military, with sleep disturbance as a hallmark manifestation. A growing
      body of research has suggested a link between obstructive sleep apnea and PTSD,
      potentially due to obstructive sleep apnea (OSA) related sleep disruption, or via
      other mechanisms. We examined the hypothesis that treatment of OSA with positive
      airway pressure would reduce PTSD symptoms over 6 months. METHODS: A prospective
      study of Veterans with confirmed PTSD and new diagnosis of OSA not yet using PAP
      therapy were recruited from a Veteran's Affairs sleep medicine clinic. All
      subjects were instructed to use PAP each night. Assessments were performed at 3
      and 6 months. The primary outcome was a reduction in PTSD symptoms at 6 months.
      RESULTS: Fifty-nine subjects were enrolled; 32 remained in the study at 6 months.
      A significant reduction in PTSD symptoms, measured by PCL-S score was observed
      over the course of the study (60.6 +/- 2.7 versus 52.3 +/- 3.2 points; p <
      0.001). Improvement was also seen in measures of sleepiness, sleep quality, and
      daytime functioning, as well as depression and quality of life. Percentage of
      nights in which PAP was used, but not mean hours used per night, was predictive
      of improvement. CONCLUSIONS: Treatment of OSA with PAP therapy is associated with
      improvement in PTSD symptoms, although the mechanism is unclear. Nonetheless, PAP
      should be considered an important component of PTSD treatment for those with
      concurrent OSA. Improving PAP compliance is a challenge in this patient
      population warranting further investigation. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, ID: NCT02019914. COMMENTARY: A commentary on this article
      appears in this issue on page 5.

PMID- 27707437
TI  - Association between Sleep Duration and Self-Reported Health Status: Findings from
      the Bhutan's Gross National Happiness Study.
AB  - STUDY OBJECTIVES: Short and long sleep durations have been found to be associated
      with chronic conditions like diabetes mellitus, hypertension and cardiovascular
      disease. However, most studies were conducted in developed countries and the
      results were inconsistent. The aim of this study is to investigate the
      association between sleep duration and self-reported health status in a
      developing country setting. METHODS: We conducted secondary data analysis of the
      2010 Gross National Happiness study of Bhutan, which was a nationwide cross
      sectional study with representative samples from rural and urban areas. The study
      included 6476 participants aged 15-98 y. The main outcome variable of interest
      was self-reported health status. Sleep duration was categorized as <= 6 h, 7 h, 8
      h, 9 h, 10 h, and >= 11 h. Multiple logistic regressions were conducted to
      investigate the association between sleep duration and self-reported health
      status. RESULTS: The mean sleep duration was 8.5 (+/- 1.65) h. Only 9% of the
      respondents slept for 7 h; 6% were short sleepers (<= 6 h) and 84% were long
      sleepers (21%, 8 h; 28%, 9 h; 22%, 10 h; 13%, >= 11 h). We found that both short
      (<= 6 h) and long sleep duration (>= 11 h) were independently associated with
      poor self-reported health status. CONCLUSIONS: This study found that people with
      shorter and longer sleep durations were more likely to report poorer health
      status.

PMID- 27707438
TI  - Validation of a Wireless, Self-Application, Ambulatory Electroencephalographic
      Sleep Monitoring Device in Healthy Volunteers.
AB  - STUDY OBJECTIVES: To evaluate the validity of an ambulatory
      electroencephalographic (EEG) monitor for the estimation of sleep continuity and
      architecture in healthy adults. METHODS: Healthy, good sleeping participants (n =
      14) were fit with both an ambulatory EEG monitor (Sleep Profiler) and a full
      polysomnography (PSG) montage. EEG recordings were gathered from both devices on
      the same night, during which sleep was permitted uninterrupted for eight hours.
      The study was set in an inpatient clinical research suite. PSG and Sleep Profiler
      records were scored by a neurologist board certified in sleep medicine, blinded
      to record identification. Agreement between the scored PSG record, the physician
      scored Sleep Profiler record, and the Sleep Profiler record scored by an
      automatic algorithm was evaluated for each sleep stage, with the PSG record
      serving as the reference. RESULTS: Results indicated strong percent agreement
      across stages. Kappa was strongest for Stage N3 and REM. Specificity was high for
      all stages; sensitivity was low for Wake and Stage N1, and high for Stage N2,
      Stage N3, and REM. Agreement indices improved for the manually scored Sleep
      Profiler record relative to the autoscore record. CONCLUSIONS: Overall, the Sleep
      Profiler yields an EEG record with comparable sleep architecture estimates to
      PSG. Future studies should evaluate agreement between devices with a clinical
      sample that has greater periods of wake in order to better understand utility of
      this device for estimating sleep continuity indices, such as sleep onset latency
      and wake after sleep onset.

PMID- 27707439
TI  - Factors Associated with Changes in Invasive and Noninvasive Positive Airway
      Pressure Therapy Settings during Pediatric Polysomnograms.
AB  - STUDY OBJECTIVES: Our aim was to identify clinical predictors associated with
      changes in settings for pediatric invasive and noninvasive positive airway
      pressure therapy, which could help inform the allocation of limited polysomnogram
      (PSG) resources. METHODS: A retrospective review was conducted in children who
      underwent one or more PSGs for technology titration. Children were included if
      they were using continuous positive airway pressure (CPAP) therapy, bilevel
      positive airway pressure (BPAP) therapy, or invasive positive pressure
      ventilation (IPPV) the night of the PSG. The primary outcome measure for the
      study were predictors of change in settings during IPPV, CPAP, and BPAP titration
      studies. RESULTS: During the study period, 274 children using CPAP, BPAP, or IPPV
      underwent one or more titration PSGs. The mean (standard deviation [SD]) age of
      the children at the time of the first titration PSG was 10.52 (5.11) y. Fifty
      percent (n = 136) of the study participants were male. Most patients underwent
      BPAP titration studies (n = 166), followed by CPAP (n = 83) and then IPPV (n =
      25). A total of 623 technology titration PSGs were completed. Reason for
      respiratory technology, type of respiratory technology, and time between
      ventilation initiation and the PSG were significant predictors of a change in
      settings in the multivariable regression model. CONCLUSIONS: Children were more
      likely to have a change in their technology settings during a PSG if there was a
      shorter period of time from the original technology initiation, if they were
      using BPAP (as compared to CPAP or IPPV) and/or if they had a primary central
      nervous system or musculoskeletal diagnosis.

PMID- 27707440
TI  - Vitamin D Improves Selected Metabolic Parameters but Not Neuropsychological or
      Quality of Life Indices in OSA: A Pilot Study.
AB  - STUDY OBJECTIVES: Our group and others have reported a high rate of vitamin D
      deficiency in obstructive sleep apnea (OSA), where vitamin D levels (25(OH) D)
      correlate negatively with OSA severity and some of its associated metabolic
      alterations. Data regarding vitamin D supplementation in OSA are lacking. We
      wanted to evaluate the effect of vitamin D3 supplementation on OSA symptoms and
      metabolic parameters. METHODS: We conducted a pilot, double-blind, randomized,
      placebo-controlled trial of daily supplementation with 4,000 IU vitamin D3 (D3)
      or placebo (PL). We studied 19 Caucasian adults (14 male, mean age 55 y, mean
      body mass index [BMI] 30.4 kg/m2) with OSA. Fifteen patients were stable on
      continuous positive airways pressure (CPAP) therapy, whereas four were CPAP
      naive. Assessments were completed at baseline and after 15 weeks of
      supplementation. Outcomes included sleepiness (Epworth Sleepiness Scale), quality
      of life (Sleep Apnea Quality of Life Inventory), fatigue (fatigue severity scale)
      and neuropsychological function (trail making test and Connor's Continuous
      Performance Test II). In addition, we assessed biochemical indices of vitamin D
      status (25(OH)D, calcium), inflammation (high sensitivity C-reactive protein, and
      lipoprotein-associated phospholipase A2), lipids (total cholesterol [low-density
      and high-density lipoprotein]) and glycemic indices (fasting glucose, oral
      glucose tolerance test). RESULTS: There was no change in BMI, medication, or CPAP
      usage. Although there was no change in neuropsychological or quality of life
      indices, we observed a significant increase in 25(OH)D (p = 0.00001) and
      significant decreases in both low-density lipoprotein (p = 0.04) and lipoprotein
      associated phospholipase A2 (p = 0.037) as well as trends toward decreased
      fasting glucose (p = 0.09) and increased high-density lipoprotein (p = 0.07) in
      the D3 group compared to PL. CONCLUSIONS: Vitamin D3 supplementation increased
      vitamin D levels and decreased metabolic markers compared to placebo. Larger
      trials are required.

PMID- 27707441
TI  - Effect of Manual Editing of Total Recording Time: Implications for Home Sleep
      Apnea Testing.
AB  - STUDY OBJECTIVES: Type 3 home sleep apnea tests may underestimate the apnea
      hypopnea index (AHI) due to overestimation of total sleep time (TST). We aimed to
      evaluate the effect of manual editing of the total recording time (TRT) on the
      TST and AHI. METHODS: Thirty 15-channel in-home polysomnography studies (AHI 0 to
      30 events/h) scored using American Academy of Sleep Medicine criteria were
      rescored by two blinded polysomnologists after data from electroencephalogram,
      electrooculogram, and electromyogram were masked. In method 1, periods of
      probable wakefulness and artifact were manually edited and removed from analysis.
      Method 2 identified TST as the TRT without manual editing. Paired t-tests were
      used to compare the TST and AHI between these methods. Sensitivity and
      specificity of each method were calculated for gold standard AHI cutoffs of >= 5
      and >= 15 events/h. RESULTS: TST (mean [standard deviation, SD]) by
      polysomnography, method 1, and method 2 was 366.0 (70.1), 447.1 (59.0), and 542
      (61.9) min, respectively. The corresponding AHI was 12.5 (8.2), 10.8 (7.0), and
      9.1 (6.1) events/h, respectively. Compared to polysomnography, both alternative
      methods overestimated the TST (method 1: mean difference [SD] 81.1 [56.1] min,
      method 2: 176.0 [89.7] min; both p < 0.001) and underestimated the AHI (method 1:
      mean difference [SD] -1.6 [3.3], method 2: -3.3 [3.9]; both p < 0.001). The
      sensitivity was 100% and 70.0% for method 1, and 91.3% and 40.0% for method 2 for
      identifying sleep-disordered breathing using AHI cutoffs of >= 5 and >= 15
      events/h, respectively. CONCLUSIONS: Manual editing of TRT reduces the
      overestimation of TST and improves the sensitivity for identifying studies with
      sleep-disordered breathing. COMMENTARY: A commentary on this article appears in
      this issue on page 9.

PMID- 27707442
TI  - Nasal Dilator Strip is an Effective Placebo Intervention for Severe Obstructive
      Sleep Apnea.
AB  - STUDY OBJECTIVES: The aim of this study was to evaluate the effects of nasal
      dilator strip (NDS) as a placebo intervention compared with continuous positive
      airway pressure (CPAP) treatment in patients with severe obstructive sleep apnea
      (OSA). METHODS: Patients were treated with both NDS and nasal CPAP. The sequence
      was randomized and interposed by 15 days of washout. Polysomnography was
      performed at baseline and on the first night of intervention with NDS and CPAP
      (titration). The Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep
      Questionnaire (FOSQ), and Beck Depression Inventory (BDI) were completed at
      baseline and at the end of both interventions. A questionnaire on the comfort and
      satisfaction (0 = no to 10 = total) was completed at the end of each
      intervention. RESULTS: Twenty-six patients with OSA were evaluated (19 male; age
      46.3 +/- 9.3 y; body mass index 33.2 +/- 5.1 kg/m2; ESS 15.8 +/- 4.1; apnea
      hypopnea index 60.7 +/- 25.2). Adherence was high in both NDS (98%) and CPAP
      interventions (94%; 5.8 +/- 1.7 h/night). In contrast to the baseline values, NDS
      intervention had no significant effect on all polysomnographic parameters, but
      NDS improved somnolence (ESS 13.0 +/- 5.4, p = 0.001) and depressive symptoms
      (BDI 7.7 +/- 6.9, p = 0.005). Reported satisfaction was significantly higher for
      CPAP than for NDS (sleep quality 9.2 +/- 0.8 vs. 6.1 +/- 2.1; wake up at morning:
      8.6 +/- 1.2 vs. 6.0 +/- 2.2; daily activities: 8.9 +/- 1.4 vs. 5.8 +/- 1.5;
      quality of life: 8.3 +/- 2.1 vs. 3.8 +/- 3.5, p < 0.001), but similar low levels
      of difficulty for both interventions were observed (1.3 +/- 2.2 vs. 0.3 +/- 1.3,
      p = 0.098). CONCLUSIONS: Our data indicate that NDS is an attractive placebo
      intervention for randomized controlled trials evaluating the effects of CPAP in
      sleepy patients with OSA.

PMID- 27707444
TI  - An Unexpected Polysomnogram Finding.

PMID- 27707443
TI  - Growing Up with Type 1 Narcolepsy: Its Anthropometric and Endocrine Features.
AB  - STUDY OBJECTIVES: To evaluate the effect of type 1 narcolepsy (NT1) on
      anthropometric and endocrine features in childhood/adolescence, focusing on
      patterns and correlates of weight, pubertal development, and growth in treated
      and untreated patients. METHODS: We collected anthropometric (height, weight,
      body mass index (BMI) z-scores), pubertal, metabolic, and endocrine data from 72
      NT1 patients at diagnosis and all available premorbid anthropometric parameters
      of patients from their pediatric files (n = 30). New measurements at 1-y
      reassessment in patients undergoing different treatments were compared with
      baseline data. RESULTS: We detected a high prevalence of overweight (29.2%),
      obesity (25%), metabolic syndrome (18.8%), and precocious puberty (16.1%), but no
      signs of linear growth alterations at diagnosis. According to anthropometric
      records, weight gain started soon after NT1 onset. At 1-y follow-up reassessment,
      sodium oxybate treatment was associated with a significant BMI z-score reduction
      (-1.29 +/- 0.30, p < 0.0005) after adjusting for baseline age, sex, sleepiness,
      and BMI. CONCLUSIONS: NT1 onset in children/adolescents is associated with rapid
      weight gain up to overweight/obesity and precocious puberty without affecting
      growth. In our study, sodium oxybate treatment resulted in a significant weight
      reduction in NT1 overweight/obese patients at 1-y follow-up.

PMID- 27707445
TI  - An Anxious 17-Year-Old Girl Who Hears Voices Only at Sleep Onset.

PMID- 27707446
TI  - Impact of Sleep-Disordered Breathing on Postoperative Outcomes: Another Brick in
      the Wall.

PMID- 27707449
TI  - Ventilatory Cycle Measurements and Loop Gain in Central Apnea in Mining Drivers
      Exposed to Intermittent Altitude.
AB  - STUDY OBJECTIVES: By measuring the apnea length, ventilatory phase, respiratory
      cycle length, and loop gain, we can further characterize the central apneas of
      high altitude (CAHA). METHODS: Sixty-three drivers of all-terrain vehicles,
      working in a Peruvian mine located at 2,020 meters above sea level (MASL), were
      evaluated. A respiratory polygraph was performed in the first night they slept at
      high altitude. None of the subjects were exposed to oxygen during the test or
      acetazolamide in the preceding days of the test. RESULTS: Sixty-three respiratory
      polygraphs were performed, and 59 were considered for analysis. Forty-six (78%)
      were normal, 6 (10%) had OSA, and 7 (12%) had CAHA. Key data from subjects
      include: residing altitude: 341 +/- 828 MASL, Lake Louise scoring: 0.4 +/- 0.8,
      Epworth score: 3.4 +/- 2.7, apneahypopnea index: 35.7 +/- 19.3, CA index: 13.4 +/
      14.2, CA length: 14.4 +/- 3.6 sec, ventilatory length: 13.5 +/- 2.9 sec, cycle
      length: 26.5 +/- 4.0 sec, ventilatory length/CA length ratio 0.9 +/- 0.3 and
      circulatory delay 13.3 +/- 2.9 sec. Duty ratio media [ventilatory duration/cycle
      duration] was 0.522 +/- 0 0.128 [0.308-0.700] and loop gain was calculated from
      the duty ratio utilizing this formula: LG = 2pi / [(2piDR-sin(2piDR)]. All
      subjects have a high loop gain media 2.415 +/- 1.761 [1.175-6.260]. Multiple
      correlations were established with loop gain values, but the only significant
      correlation detected was between central apnea index and loop gain. CONCLUSIONS:
      Twelve percent of the studied population had CAHA. Measurements of respiratory
      cycle in workers with CAHA are more similar to idiopathic central apneas rather
      than Hunter-Cheyne-Stokes respiration. Also, there was a high degree of
      correlation between severity of central apnea and the degree of loop gain. The
      abnormal breathing patterns in those subjects could affect the sleep quality and
      potentially increase the risk for work accidents.

PMID- 27707448
TI  - Reliability of Actigraphy and Subjective Sleep Measurements in Adults: The Design
      of Sleep Assessments.
AB  - STUDY OBJECTIVES: The aim of the study was to investigate how many nights of
      measurement are needed for a reliable measure of sleep in a working population
      including adult women and men. METHODS: In all, 54 individuals participated in
      the study. Sleep was assessed for 7 consecutive nights using actigraphy as an
      objective measure, and the Karolinska sleep diary for a subjective measure of
      quality. Using intra-class correlation and the Spearman-Brown formula,
      calculations of how many nights of measurements were required for a reliable
      measure were performed. Differences in reliability according to whether or not
      weekend measurements were included were investigated. Further, the correlation
      between objectively (actigraphy) measured sleep and subjectively measured sleep
      quality was studied over the different days of the week. RESULTS/CONCLUSIONS: The
      results concerning actigraphy sleep measures suggest that data from at least 2
      nights are to be recommended when assessing sleep percent and at least 5 nights
      when assessing sleep efficiency. For actigraphy-measured total sleep time, more
      than 7 nights are needed. At least 6 nights of measurements are required for a
      reliable measure of self-reported sleep. Fewer nights (days) are required if
      measurements include only week nights. Overall, there was a low correlation
      between the investigated actigraphy sleep parameters and subjective sleep
      quality, suggesting that the two methods of measurement capture different
      dimensions of sleep.

PMID- 27707447
TI  - Consensus Statement of the American Academy of Sleep Medicine on the Recommended
      Amount of Sleep for Healthy Children: Methodology and Discussion.
AB  - ABSTRACT: Members of the American Academy of Sleep Medicine developed consensus
      recommendations for the amount of sleep needed to promote optimal health in
      children and adolescents using a modified RAND Appropriateness Method. After
      review of 864 published articles, the following sleep durations are recommended:
      Infants 4 months to 12 months should sleep 12 to 16 hours per 24 hours (including
      naps) on a regular basis to promote optimal health. Children 1 to 2 years of age
      should sleep 11 to 14 hours per 24 hours (including naps) on a regular basis to
      promote optimal health. Children 3 to 5 years of age should sleep 10 to 13 hours
      per 24 hours (including naps) on a regular basis to promote optimal health.
      Children 6 to 12 years of age should sleep 9 to 12 hours per 24 hours on a
      regular basis to promote optimal health. Teenagers 13 to 18 years of age should
      sleep 8 to 10 hours per 24 hours on a regular basis to promote optimal health.
      Sleeping the number of recommended hours on a regular basis is associated with
      better health outcomes including: improved attention, behavior, learning, memory,
      emotional regulation, quality of life, and mental and physical health. Regularly
      sleeping fewer than the number of recommended hours is associated with attention,
      behavior, and learning problems. Insufficient sleep also increases the risk of
      accidents, injuries, hypertension, obesity, diabetes, and depression.
      Insufficient sleep in teenagers is associated with increased risk of self-harm,
      suicidal thoughts, and suicide attempts. COMMENTARY: A commentary on this article
      apears in this issue on page 1439.

PMID- 27707451
TI  - They need to be recognized as a person in everyday life: Teachers' and helpers'
      experiences of teacher-student relationships in upper secondary school.
AB  - The aim of this study was to explore how teachers and helpers experience that
      teacher-student relationship (TSR) is developed and promoted in upper secondary
      school.We also explored their experiences of qualities of TSR with students with
      mental health problems or at risk of dropping out. The study used a qualitative
      and participative approach; key stakeholders were included as co-researchers.
      Focus group interviews were held with 27 teachers and helpers. A thematic
      analysis was conducted. The participants' descriptions of important experiential
      dimensions of TSR were clustered around four themes: (1) to be recognized as a
      person with strengths and challenges in everyday life, (2) collaborative
      relationships between students and teachers, (3) flexible boundaries in the
      relationship between teachers and students and (4) organization of classes and
      procedures set the stage for TSR. Collaborative, emotional and contextual
      qualities were found important to the development of TSR in upper secondary
      school. Experiences of negative qualities of TSR can contribute to push students
      out of school. Teachers and helpers experience that TSR may have the potential to
      play a role in promoting mental health in students' everyday life.

PMID- 27707450
TI  - Effects of Yoga and Aerobic Exercise on Actigraphic Sleep Parameters in
      Menopausal Women with Hot Flashes.
AB  - STUDY OBJECTIVES: To determine effects of yoga and aerobic exercise compared with
      usual activity on objective assessments of sleep in midlife women. METHODS:
      Secondary analyses of a randomized controlled trial in the Menopause Strategies:
      Finding Lasting Answers for Symptoms and Health (MsFLASH) network conducted among
      186 late transition and postmenopausal women aged 40-62 y with hot flashes. Women
      were randomized to 12 w of yoga, supervised aerobic exercise, or usual activity.
      The mean and coefficient of variation (CV) of change in actigraph sleep measures
      from each intervention group were compared to the usual activity group using
      linear regression models. RESULTS: Baseline values of the primary sleep measures
      for the entire sample were mean total sleep time (TST) = 407.5 +/- 56.7 min; mean
      wake after sleep onset (WASO) = 54.6 +/- 21.8 min; mean CV for WASO = 37.7 +/-
      18.7 and mean CV for number of long awakenings > 5 min = 81.5 +/- 46.9. Changes
      in the actigraphic sleep outcomes from baseline to weeks 11-12 were small, and
      none differed between groups. In an exploratory analysis, women with baseline
      Pittsburgh Sleep Quality Index higher than 8 had significantly reduced TST-CV
      following yoga compared with usual activity. CONCLUSIONS: This study adds to the
      currently scant literature on objective sleep outcomes from yoga and aerobic
      exercise interventions for this population. Although small effects on self
      reported sleep quality were previously reported, the interventions had no
      statistically significant effects on actigraph measures, except for potentially
      improved sleep stability with yoga in women with poor self-reported sleep
      quality.

PMID- 27707452
TI  - Female genital mutilation: a systematic review of research on its economic and
      social impacts across four decades.
AB  - BACKGROUND: Global efforts to end female genital mutilation (FGM) have
      intensified in recent decades because of the rising awareness that such a
      practice is an act of extreme violence against women and girls. Articles on FGM
      have been published highlighting the combined efforts of international and non
      governmental organizations, governments, as well as religious and civil society
      groups to end the practice. However, the consequences of this research are not
      well known, and it seems that the socioeconomic aspects of the practice are
      underreported. OBJECTIVE: This review aims to characterize over a 40-year period
      the scientific output on the consequences of FGM in African countries, the most
      affected region known for the high prevalence of FGM, and review data on the
      socioeconomic consequences of the practice. DESIGN: A systematic review of
      literature was done, looking at the following databases: PubMed, Embase, CINAHL,
      BDSP, Web of Science, PsycINFO, FRANCIS, Sociological Abstracts, WHOLIS, RERO,
      and SAPHIR. The analysis was limited to articles concerning the African
      continent, published in English and French, from January 1, 1972, to December 31,
      2011. RESULTS: One hundred ninety-eight articles were reviewed. More than half of
      the articles were published during the last decade of the study period. The
      majority of papers were published in biomedical journals (64.1%). Most studies
      looked at Africa as a region (33.3%). Nigeria was the single country most
      investigated (19.2%), followed by Egypt (10.6%). Most first authors were
      affiliated to non-African countries (60.6%): among them 21.2% were US-based, 4%
      were from African institutions, and 16.2% from Nigeria.The medical and
      psychological consequences (51.5%) and the prevalence and ethics of the practice
      (34.4%) were the most frequently investigated topics. The socioeconomic
      consequences were addressed in a minority of the papers (14.1%): they were
      classified into direct economic consequences (2.5%), school attendance (1%),
      marriageability (2%), sexual and marital consequences (3.5%), fertility (2.5%),
      domestic violence (1%), and discrimination (1.5%). CONCLUSIONS: The publication
      of articles on the consequences of FGM is increasing, but there is little
      research on the socioeconomic consequences of the practice. More scientific data
      focusing on this dimension is necessary to strengthen prevention, advocacy, and
      intervention campaigns.

PMID- 27707453
TI  - Proprietary tomato extract improves metabolic response to high-fat meal in
      healthy normal weight subjects.
AB  - BACKGROUND: Low-density lipoprotein (LDL) oxidation is a risk factor for
      atherosclerosis. Lycopene and tomato-based products have been described as potent
      inhibitors of LDL oxidation. OBJECTIVES: To evaluate the effect of a 2-week
      supplementation with a carotenoid-rich tomato extract (CRTE) standardized for a
      1:1 ratio of lycopene and phytosterols, on post-prandial LDL oxidation after a
      high-fat meal. DESIGN: In a randomized, double-blind, parallel-groups, placebo
      controlled study, 146 healthy normal weight individuals were randomly assigned to
      a daily dose of CRTE standardized for tomato phytonutrients or placebo during 2
      weeks. Oxidized LDL (OxLDL), glucose, insulin, and triglyceride (TG) responses
      were measured for 8 h after ingestion of a high-fat meal before and at the end of
      intervention. RESULTS: Plasma lycopene, phytofluene, and phytoene were increased
      throughout the study period in the CRTE group compared to placebo. CRTE ingestion
      significantly improved changes in OxLDL response to high-fat meal compared to
      placebo after 2 weeks (p<0.0001). Changes observed in glucose, insulin, and TG
      responses were not statistically significant after 2 weeks of supplementation,
      although together they may suggest a trend of favorable effect on metabolic
      outcomes after a high-fat meal. CONCLUSIONS: Two-week supplementation with CRTE
      increased carotenoids levels in plasma and improved oxidized LDL response to a
      high-fat meal in healthy normal weight individuals.

PMID- 27707454
TI  - Yellow fever vaccine-associated neurotropic disease (YEL-AND) - A case report.
AB  - Yellow fever (YF) is a mosquito-borne viral hemorrhagic fever, which is a serious
      and potentially fatal disease with no specific antiviral treatment that can be
      effectively prevented by an attenuated vaccine (YEL). Despite the long history of
      safe and efficacious YF vaccination, sporadic case reports of serious adverse
      events (SAEs) have been reported, including yellow fever vaccine-associated
      neurotropic disease (YEL-AND). YEL-AND usually appears within one month of YF
      vaccination, manifesting as meningoencephalitis, Guillain-Barre syndrome (GBS) or
      acute disseminated encephalomyelitis (ADEM). We report a case of YEL-AND with
      meningitis presentation in a 39-year-old Caucasian man without evidence of
      significant risk factors, which was confirmed by the presence of the YF virus and
      specific immunoglobulin G (IgG) antibodies in the cerebrospinal fluid (CSF). In
      conclusion, we should stress the importance of balancing the risk of SAEs
      associated with the vaccine and the benefits of YF vaccination for each patient
      individually.

PMID- 27707455
TI  - Focus on latent tuberculosis.

PMID- 27707456
TI  - Lessons from LAVOLTA.

PMID- 27707457
TI  - Usual interstitial pneumonia pattern in the diagnosis of idiopathic pulmonary
      fibrosis?

PMID- 27707458
TI  - 2016 annual congress of the European Respiratory Society.

PMID- 27707459
TI  - Rapid changes in the respiratory environment in Albania.

PMID- 27707461
TI  - Focusing on breath.

PMID- 27707460
TI  - Unconventional natural gas development and respiratory health.

PMID- 27707462
TI  - The challenge of reducing smoking in people with serious mental illness.
AB  - The high prevalence of smoking in people with serious mental illness contributes
      substantially to the disproportionately high morbidity and premature mortality in
      this population. There is an urgent need to help people with serious mental
      illness to quit smoking. We discuss competing explanations for the high
      prevalence of smoking in people with serious mental illness and the effectiveness
      of available smoking cessation interventions. We propose trials of harm reduction
      options, such as nicotine replacement therapy and electronic cigarettes (e
      cigarettes), as long-term substitutes for cigarettes in smokers with serious
      mental illness who are unable to quit smoking. We also propose that smoke-free
      psychiatric units provide smoking cessation support on patient admission to the
      hospital and after discharge.

PMID- 27707463
TI  - COPD case finding: effective, but also cost-effective?

PMID- 27707464
TI  - Corrections.

PMID- 27707465
TI  - Corrections.

PMID- 27707466
TI  - COPD case finding: effective, but also cost-effective? - Authors' reply.

PMID- 27707467
TI  - Prognostic role of hyponatremia in acute heart failure.

PMID- 27707469
TI  - Description of plastic remains found in the stomach contents of the jumbo squid
      Dosidicus gigas landed in Ecuador during 2014.
AB  - Squids are active and opportunistic predators that feed on a wide range of prey.
      Their active movements in the water column and their voracity promote a high
      consumption of food. In the pelagic environment off Ecuador, marine pollution is
      characterized by plastic debris with a mainland origin, including plastics trash
      of fishing gears. The objective of this work was to describe the presence of
      plastic remains in the stomach contents of Dosidicus gigas caught off the coast
      of Ecuador. Results demonstrated that 12% of the stomachs contained plastic
      remains. These plastics were identified as multifilament of polyethylene lines
      and polyvinyl chloride remains. Findings of this work could be related to an
      increase in the discharge of solid materials in the water column, increasing the
      probability to be ingested by the jumbo squid.

PMID- 27707468
TI  - Does Sudden Unexplained Nocturnal Death Syndrome Remain the Autopsy-Negative
      Disorder: A Gross, Microscopic, and Molecular Autopsy Investigation in Southern
      China.
AB  - OBJECTIVE: To look for previously unrecognized cardiac structural abnormalities
      and address the genetic cause for sudden unexplained nocturnal death syndrome
      (SUNDS). METHODS: Data for 148 SUNDS victims and 444 controls (matched 1:3 on
      sex, race, and age of death within 1 year) were collected from Sun Yat-sen
      University from January 1, 1998, to December 31, 2014, to search morphological
      changes. An additional 17 patients with Brugada syndrome (BrS) collected from
      January 1, 2006, to December 31, 2014, served as a comparative disease cohort.
      Target-captured next-generation sequencing for 80 genes associated with
      arrhythmia/cardiomyopathy was performed in 44 SUNDS victims and 17 patients with
      BrS to characterize the molecular spectrum. RESULTS: The SUNDS victims had slight
      but statistically significant increased heart weight and valve circumference
      compared with controls. Twelve of 44 SUNDS victims (SCN5A, SCN1B, CACNB2,
      CACNA1C, AKAP9, KCNQ1, KCNH2, KCNJ5, GATA4, NUP155, ABCC9) and 6 of 17 patients
      with BrS (SCN5A, CACNA1C; P>.05) carried rare variants in primary arrhythmia
      susceptibility genes. Only 2 of 44 SUNDS cases compared with 5 of 17 patients
      with BrS hosted a rare variant in the most common BrS-causing gene, SCN5A
      (P=.01). Using the strict American College of Medical Genetics guideline-based
      definition, it was found that only 2 of 44 (KCNQ1) SUNDS and 3 of 17 (SCN5A)
      patients with BrS hosted a "(likely) pathogenic" variant. Fourteen of 44 SUNDS
      cases with cardiomyopathy-related variants had a subtle but significantly
      decreased circumference of cardiac valves, and tended to die on average 5 to 6
      years younger compared with the remaining 30 cases (P=.02). CONCLUSION: We
      present the first comprehensive autopsy evidence that SUNDS victims may have
      concealed cardiac morphological changes. SUNDS and BrS may result from different
      molecular pathological underpinnings. The distinct association between
      cardiomyopathy-related rare variants and SUNDS warrants further investigation.

PMID- 27707470
TI  - Sustainability and the Spanish port system. Analysis of the relationship between
      economic and environmental indicators.
AB  - Research into the methodological development of alternative systems of
      sustainability measures is recent. In understanding sustainable development in a
      multi-dimensional sense, one of the most significant advances was the
      construction of Synthetic Indexes, applicable to different spatial spheres or to
      organisations, businesses, institutions, etc. The Spanish port system of general
      interest comprises 46 ports integrated in 28 Port Authorities, which in 2014
      moved 482,000,000t of goods and more than 28 million passengers. This gives an
      idea of its importance for the Spanish economy. Using a derivation of the
      procedure used to calculate the Port Sustainability Synthetic Index, in this
      research the analysis of the relationship that exists between the findings
      obtained for the economic and environmental dimensions is used. This enables the
      existence of links between ports and economic and environmental indicators for a
      sample of 16 Port Authorities of Spain to be verified.

PMID- 27707471
TI  - Concentration and congener pattern of polychlorinated biphenyls in blubber and
      liver of Hubbs' beaked whale (Mesoplodon carlhubbsi), using a sulfoxide and an Ag
      ION solid phase extraction cartridge as a simplified cleanup technique for
      biological samples.
AB  - We performed the first known study of polychlorinated biphenyls (PCBs)
      concentrations and patterns in the blubber and liver of a Hubbs' beaked whale.
      Samples were pretreated with SupelcleanTM sulfoxide and Discovery(r) Ag-ION solid
      phase extraction cartridges to remove whale oil. PCB concentrations in the
      blubber and liver were 13,000 and 7300ng/g lipid, respectively. Highly poisonous
      congeners such as dioxin-like (DL) PCBs tended to accumulate in the liver. The
      toxic equivalents (TEQ) of DL-PCBs in the liver (740pg-TEQ/g lipid) were higher
      than those in the blubber (74pg-TEQ/g lipid). The blubber and liver samples
      showed that hexachlorinated biphenyls were dominant among homologues, and PCB-153
      was dominant among congeners. Several congeners accumulated disproportionately in
      the blubber and the liver (PCB-28, 52, 74, 99, and 118), while others did not
      persist (PCB-31, 70, and 110). This indicates that PCBs are metabolized
      differently according to their specific composition.

PMID- 27707472
TI  - The impact of wastewater treatment effluent on microbial biomasses and
      diversities in coastal sediment microcosms of Hangzhou Bay.
AB  - Disposal of wastewater treatment plant (WWTP) effluent into sea, a typical
      anthropogenic disturbance, may influence many environmental factors and change
      the coastal microbial community structure. In this study, by setting up coastal
      sediment microcosms perturbed by WWTP effluent, the changes of microbial
      community structure under different degree of disturbances were investigated.
      Quantitative PCR (qPCR) and terminal restriction fragment length polymorphism (T
      RFLP) were used to analyzed the biomass and biodiversity. High throughput
      sequencing analysis was used to identify the classification of the
      microorganisms. Our study suggested that low ratio of WWTP effluent may stimulate
      dominant species, which increase the biomass but decrease the biodiversity; while
      high ratio of WWTP effluent may depress all species, which decrease the biomass
      but increase the biodiversity. In other words, the impact was dose-dependent. The
      changes of microbial community structure may provide a metric for water
      environmental assessment and pollution control.

PMID- 27707474
TI  - Sexual behaviour in young people: healthy or harmful?

PMID- 27707473
TI  - How can registries and innovation improve surgical care?

PMID- 27707475
TI  - Patient need versus evidence: a balancing act.

PMID- 27707476
TI  - Early mobilisation in ICU is far more than just exercise.

PMID- 27707477
TI  - Clear-lens extraction as a treatment for primary angle closure.

PMID- 27707478
TI  - Surgical registries for advancing quality and device surveillance.

PMID- 27707479
TI  - New hopes for accountability for women, children, and adolescent health.

PMID- 27707480
TI  - Offline: Global health-tipping into irrelevance.

PMID- 27707481
TI  - Six candidates compete in WHO Director-General election.

PMID- 27707482
TI  - Mixed results for refugees and migrants at UN meetings.

PMID- 27707483
TI  - UN declaration on antimicrobial resistance lacks targets.

PMID- 27707485
TI  - Jane Blazeby: passionate leader in evidence-based surgery.

PMID- 27707484
TI  - Pakistan takes small steps towards tackling burn injuries.

PMID- 27707486
TI  - The Lancet Technology: 3D printing for instruments, models, and organs?

PMID- 27707487
TI  - Deferred stenting in acute ST elevation myocardial infarction - Authors' reply.

PMID- 27707488
TI  - Deferred stenting in acute ST elevation myocardial infarction.

PMID- 27707489
TI  - The CORONIS trial on caesarean section.

PMID- 27707490
TI  - The CORONIS trial on caesarean section.

PMID- 27707491
TI  - The CORONIS trial on caesarean section - Authors' reply.

PMID- 27707492
TI  - Department of Error.

PMID- 27707494
TI  - Department of Error.

PMID- 27707493
TI  - Department of Error.

PMID- 27707495
TI  - The first Science Cafe in Laos.

PMID- 27707496
TI  - Early, goal-directed mobilisation in the surgical intensive care unit: a
      randomised controlled trial.
AB  - BACKGROUND: Immobilisation predicts adverse outcomes in patients in the surgical
      intensive care unit (SICU). Attempts to mobilise critically ill patients early
      after surgery are frequently restricted, but we tested whether early mobilisation
      leads to improved mobility, decreased SICU length of stay, and increased
      functional independence of patients at hospital discharge. METHODS: We did a
      multicentre, international, parallel-group, assessor-blinded, randomised
      controlled trial in SICUs of five university hospitals in Austria (n=1), Germany
      (n=1), and the USA (n=3). Eligible patients (aged 18 years or older, who had been
      mechanically ventilated for <48 h, and were expected to require mechanical
      ventilation for >=24 h) were randomly assigned (1:1) by use of a stratified block
      randomisation via restricted web platform to standard of care (control) or early,
      goal-directed mobilisation using an inter-professional approach of closed-loop
      communication and the SICU optimal mobilisation score (SOMS) algorithm
      (intervention), which describes patients' mobilisation capacity on a numerical
      rating scale ranging from 0 (no mobilisation) to 4 (ambulation). We had three
      main outcomes hierarchically tested in a prespecified order: the mean SOMS level
      patients achieved during their SICU stay (primary outcome), and patient's length
      of stay on SICU and the mini-modified functional independence measure score
      (mmFIM) at hospital discharge (both secondary outcomes). This trial is registered
      with ClinicalTrials.gov (NCT01363102). FINDINGS: Between July 1, 2011, and Nov 4,
      2015, we randomly assigned 200 patients to receive standard treatment (control;
      n=96) or intervention (n=104). Intention-to-treat analysis showed that the
      intervention improved the mobilisation level (mean achieved SOMS 2.2 [SD 1.0] in
      intervention group vs 1.5 [0.8] in control group, p<0.0001), decreased SICU
      length of stay (mean 7 days [SD 5-12] in intervention group vs 10 days [6-15] in
      control group, p=0.0054), and improved functional mobility at hospital discharge
      (mmFIM score 8 [4-8] in intervention group vs 5 [2-8] in control group,
      p=0.0002). More adverse events were reported in the intervention group (25 cases
      [2.8%]) than in the control group (ten cases [0.8%]); no serious adverse events
      were observed. Before hospital discharge 25 patients died (17 [16%] in the
      intervention group, eight [8%] in the control group). 3 months after hospital
      discharge 36 patients died (21 [22%] in the intervention group, 15 [17%] in the
      control group). INTERPRETATION: Early, goal-directed mobilisation improved
      patient mobilisation throughout SICU admission, shortened patient length of stay
      in the SICU, and improved patients' functional mobility at hospital discharge.
      FUNDING: Jeffrey and Judy Buzen.

PMID- 27707497
TI  - Effectiveness of early lens extraction for the treatment of primary angle-closure
      glaucoma (EAGLE): a randomised controlled trial.
AB  - BACKGROUND: Primary angle-closure glaucoma is a leading cause of irreversible
      blindness worldwide. In early-stage disease, intraocular pressure is raised
      without visual loss. Because the crystalline lens has a major mechanistic role,
      lens extraction might be a useful initial treatment. METHODS: From Jan 8, 2009,
      to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five
      countries. Randomisation was done by a web-based application. Patients were
      assigned to undergo clear-lens extraction or receive standard care with laser
      peripheral iridotomy and topical medical treatment. Eligible patients were aged
      50 years or older, did not have cataracts, and had newly diagnosed primary angle
      closure with intraocular pressure 30 mm Hg or greater or primary angle-closure
      glaucoma. The co-primary endpoints were patient-reported health status,
      intraocular pressure, and incremental cost-effectiveness ratio per quality
      adjusted life-year gained 36 months after treatment. Analysis was by intention to
      treat. This study is registered, number ISRCTN44464607. FINDINGS: Of 419
      participants enrolled, 155 had primary angle closure and 263 primary angle
      closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard
      care, of whom 351 (84%) had complete data on health status and 366 (87%) on
      intraocular pressure. The mean health status score (0.87 [SD 0.12]), assessed
      with the European Quality of Life-5 Dimensions questionnaire, was 0.052 higher
      (95% CI 0.015-0.088, p=0.005) and mean intraocular pressure (16.6 [SD 3.5] mm Hg)
      1.18 mm Hg lower (95% CI -1.99 to -0.38, p=0.004) after clear-lens extraction
      than after standard care. The incremental cost-effectiveness ratio was L14 284
      for initial lens extraction versus standard care. Irreversible loss of vision
      occurred in one participant who underwent clear-lens extraction and three who
      received standard care. No patients had serious adverse events. INTERPRETATION:
      Clear-lens extraction showed greater efficacy and was more cost-effective than
      laser peripheral iridotomy, and should be considered as an option for first-line
      treatment. FUNDING: Medical Research Council.

PMID- 27707498
TI  - The metabolic stress response to burn trauma: current understanding and
      therapies.
AB  - Major burns provoke a profound stress response, which is unrivalled in terms of
      its magnitude and duration. Evidence suggests that the pathophysiological stress
      response to severe burn trauma persists for several years after injury. Thus,
      there is a pressing need for novel strategies that mitigate this response and
      restore normal metabolic function in patients with burns. This is the first in a
      Series of three papers about the care of people with burns. In this paper, we
      review the current knowledge of the stress response to burn trauma, with a focus
      on hypermetabolism, muscle wasting, and stress-induced diabetes. We highlight
      recent developments and important knowledge gaps that need to be pursued to
      develop novel therapeutic strategies to improve outcomes in burn survivors.

PMID- 27707501
TI  - The race to become the next UN Secretary-General.

PMID- 27707499
TI  - Hypertrophic scarring: the greatest unmet challenge after burn injury.
AB  - Improvements in acute burn care have enabled patients to survive massive burns
      that would have once been fatal. Now up to 70% of patients develop hypertrophic
      scars after burns. The functional and psychosocial sequelae remain a major
      rehabilitative challenge, decreasing quality of life and delaying reintegration
      into society. Approaches to optimise healing potential of burn wounds use
      targeted wound care and surgery to minimise the development of hypertrophic
      scarring. Such approaches often fail, and modulation of the established scar is
      continued although the optimal indication, timing, and combination of therapies
      have yet to be established. The need for novel treatments is paramount, and
      future efforts to improve outcomes and quality of life should include
      optimisation of wound healing to attenuate or prevent hypertrophic scarring, well
      designed trials to confirm treatment efficacy, and further elucidation of
      molecular mechanisms to allow development of new preventive and therapeutic
      strategies.

PMID- 27707502
TI  - Leucite and cooling rate effect on porcelain-zirconia mechanical behavior.
AB  - OBJECTIVE: This study investigated the influence of the cooling protocol on the
      mechanical behavior of Y-TZP veneered with porcelain with different compositions.
      The tested hypotheses were: (1) Y-TZP infrastructures veneered with porcelain
      containing leucite in its composition presents higher flexural strength (sigma)
      and reliability (m), and (2) slow cooling protocol results in greater sigma and
      m. METHODS: A total of 120 bilayer porcelain-Y-TZP bar-shaped specimens were
      prepared with the dimensions of 1.8mm (0.8mm Y-TZP+/-1.0mm
      porcelain)*4.0mm*16.0mm. Specimens were divided into four groups (n=30) according
      to the porcelain composition (containing or not leucite) and cooling protocol.
      Fast cooling was performed by opening the furnace chamber at sintering
      temperature. For the slow cooling, the chamber was maintained closed until it
      reached the room temperature. Specimens were tested in three-point bending with
      the porcelain surface under tension using a universal testing machine, in 37
      degrees C water, at 0.5mm/min crosshead speed. Data were analyzed by two-way
      ANOVA, Tukey post-hoc test (alpha=0.05) and Weibull. RESULTS: Y-TZP veneered with
      porcelains with different microstructural composition presented similar sigma and
      m values (p=0.718). The cooling protocol had no influence on the sigma and m
      values of the experimental groups (p=0.718). Cracking represented 95% of
      failures, whereas the initial flaw propagated from the porcelain surface towards
      the interface. SIGNIFICANCE: Y-TZP veneered with porcelain containing or not
      leucite present similar mechanical behavior and, at 1-mm thickness, is not
      sensitive to the cooling protocol.

PMID- 27707503
TI  - Reducing the effect of polymerization shrinkage of temporary fixed dental
      prostheses by using different materials and fabrication techniques.
AB  - OBJECTIVE: The aim of this laboratory study was to evaluate the horizontal and
      vertical effects of the polymerization shrinkage of three-unit temporary fixed
      dental prostheses (FDPs) on the position of the prepared teeth. In addition, the
      reduction of these effects by using different fabrication techniques was
      evaluated. METHODS: A total of 192 temporary FDPs were fabricated using one
      methacrylate (MA) and two dimethacrylate (DMA) materials. Each material group
      (n=64) was divided into two groups according to the fabrication methods (M1:
      curing on the prepared teeth, M2: curing in a silicone mold). Each fabrication
      group was divided into four subgroups (n=8) according to the relining method used
      (B: no relining, S: spacer foil 300MUm, DG: grinding-out with 500MUm cutting
      depth, and FG: free grinding). The experimental apparatus consisted of two
      abutment teeth lowered at right angles into a silicone mold. One prepared tooth
      was embedded in silicone to simulate the periodontium and permit slight
      horizontal tooth movement. The dimensional changes were recorded with an optical
      microscope. The test images were superimposed and measured using image analysis
      software. RESULTS: The statistical analysis showed that there were significantly
      higher horizontal changes for the MA than the DMA resins in M1, while there was
      none in M2. Regarding the vertical changes, there were significant differences
      between the baseline group and all relining and fabrication groups in all
      materials. SIGNIFICANCE: Relining of directly fabricated temporary FDPs
      significantly reduces the effect of polymerization shrinkage and thus secures the
      position of the prepared teeth.

PMID- 27707500
TI  - Pathophysiology, research challenges, and clinical management of smoke inhalation
      injury.
AB  - Smoke inhalation injury is a serious medical problem that increases morbidity and
      mortality after severe burns. However, relatively little attention has been paid
      to this devastating condition, and the bulk of research is limited to preclinical
      basic science studies. Moreover, no worldwide consensus criteria exist for its
      diagnosis, severity grading, and prognosis. Therapeutic approaches are highly
      variable depending on the country and burn centre or hospital. In this Series
      paper, we discuss understanding of the pathophysiology of smoke inhalation
      injury, the best evidence-based treatments, and challenges and future directions
      in diagnostics and management.

PMID- 27707504
TI  - Right middle lobe torsion after right upper lobectomy in a patient with an
      undiagnosed middle lobe syndrome.

PMID- 27707505
TI  - Dose painting by numbers based on retrospectively determined recurrence
      probabilities.
AB  - BACKGROUND AND PURPOSE: The aim of this study is to derive "dose painting by
      numbers" prescriptions from retrospectively observed recurrence volumes in a
      patient group treated with conventional radiotherapy for head and neck squamous
      cell carcinoma. MATERIALS AND METHODS: The spatial relation between
      retrospectively observed recurrence volumes and pre-treatment standardized uptake
      values (SUV) from fluorodeoxyglucose positron emission tomography (FDG-PET)
      imaging was determined. Based on this information we derived SUV driven dose
      response functions and used these to optimize ideal dose redistributions under
      the constraint of equal average dose to the tumor volumes as for a conventional
      treatment. The response functions were also implemented into a treatment planning
      system for realistic dose optimization. RESULTS: The calculated tumor control
      probabilities (TCP) increased between 0.1-14.6% by the ideal dose redistributions
      for all included patients, where patients with larger and more heterogeneous
      tumors got greater increases than smaller and more homogeneous tumors.
      CONCLUSIONS: Dose painting prescriptions can be derived from retrospectively
      observed recurrence volumes spatial relation to pre-treatment FDG-PET image data.
      The ideal dose redistributions could significantly increase the TCP for patients
      with large tumor volumes and large spread in SUV from FDG-PET. The results yield
      a basis for prospective studies to determine the clinical value for dose painting
      of head and neck squamous cell carcinomas.

PMID- 27707506
TI  - Fast interaction between AMPA and NMDA receptors by intracellular calcium.
AB  - Suppression of NMDA receptor (NMDAR)-mediated currents by intracellular Ca2+ has
      been described as a negative feedback loop in NMDAR modulation. In the time scale
      of tenths of milliseconds the depth of the suppression does not depend on the
      Ca2+ source. It may be caused by Ca2+ influx through voltage-gated calcium
      channels, NMDAR channels or release from intracellular stores. However, NMDARs
      are often co-expressed in synapses with Ca2+-permeable AMPA receptors (AMPARs).
      Due to significant differences in activation kinetics between these two types of
      glutamate receptors (GluRs), Ca2+ entry through AMPARs precedes full activation
      of NMDARs, and therefore, might have an impact on the amplitude of NMDAR-mediated
      currents. The study of Ca2+-mediated crosstalk between AMPAR and NMDAR in native
      synapses is challenging due to high NMDAR Ca2+ permeability. Therefore,
      recombinant Ca2+-permeable AMPAR and Ca2+-impermeable NMDAR mutant channels were
      co-expressed in HEK 293 cells to examine their interaction. An AMPAR-mediated
      increase in intracellular Ca2+ concentration ([Ca2+]i) reversibly reduced the
      size of NMDAR-mediated whole-cell currents. The time course of the NMDAR channel
      inactivation and recovery from inactivation followed the time course of the
      [Ca2+]i transient. When brief (1ms) pulses of glutamate were applied to outside
      out patches, the degree of NMDAR inactivation increased with the increase in
      charge carried by the currents through co-activated AMPARs. However, AMPAR
      mediated NMDAR inactivation was abolished in the presence of intracellular fast
      Ca2+ buffer BAPTA or in Ca2+-free extracellular solution. We conclude that Ca2+
      entering through AMPARs inactivates co-localized NMDARs in the time range of
      excitatory postsynaptic currents.

PMID- 27707507
TI  - Rift Valley fever trasmission dynamics described by compartmental models.
AB  - Rift Valley fever (RVF) is one of the most important zoonotic Transboundary
      Animal Diseases able to cross international borders and cause devastating effect
      on animal health and food security. Climate changes and the presence of competent
      vectors in the most of the current RVF-free temperate countries strongly support
      the inclusion of RVF virus (RVFV) among the most significant emerging viral
      threats for public and animal health. The transmission of RVFV is driven by
      complex eco-climatic factors making the epidemiology of RVF infection difficult
      to study and to understand. Mathematical, statistical and spatial models are
      often used to explain the mechanisms underlying these biological processes,
      providing new and effective tools to plan measures for public health protection.
      In this paper we performed a systematic literature review on RVF published papers
      with the aim of identifying and describing the most recent papers developing
      compartmental models for the study of RVFV transmission dynamics.

PMID- 27707508
TI  - Tracing the use of evaluations in legislative processes in Swiss cantonal
      parliaments.
AB  - Several studies have challenged the notion that members of parliament use
      information from evaluations to make policies. However, it is also argued that
      the function of evaluations in an inherently political context such as parliament
      is to provide arguments and justifications rather than simply supply information
      for policymaking. This paper provides a fine-grained account of the use of
      evaluations by members of parliament in the context of political conflict.
      Previous research has highlighted the importance of this factor, but the findings
      are controversial. Here, four case studies of policy processes in two Swiss
      cantonal parliaments illustrate that political conflict is highly context
      specific. Documentary analysis and interviews show that the members of parliament
      used evaluations to inform themselves as well as to gain political support in the
      moderately contested case. This both supports and challenges previous research.
      Comparing the cases reveals that the administration's use of evaluations strongly
      influences their use in the non-professional cantonal parliaments. However,
      Switzerland's semi-direct democracy and its conflict-resolving mechanisms shape
      and limit this role, particularly if political conflict is high.

PMID- 27707509
TI  - Comparative Pharmacokinetic Analysis of Thiamine and Its Phosphorylated
      Metabolites Administered as Multivitamin Preparations.
AB  - PURPOSE: Fursultiamine and benfotiamine are lipophilic thiamine derivatives used
      as oral sources of thiamine. Although there are many publications on the
      pharmacokinetic (PK) properties of thiamine-containing products, no direct
      comparisons between these agents . We aimed to compare the PK profiles of these
      lipophilic thiamine derivatives and to compare the extent of the increase in
      bioavailability to that of naive thiamine. METHODS: Two randomized, single-dose,
      2-way crossover, full PK studies were conducted in healthy Korean male subjects
      (n = 24 per group). Among the test compounds, fursultiamine was compared with
      benfotiamine (reference A in study A) and thiamine nitrate (reference B in study
      B). All formulations were multivitamin preparations containing the test or
      reference formulation as the major thiamine source. In study A, the plasma and
      hemolysate concentrations of thiamine and its metabolites were measured, while
      only the plasma thiamine concentration was assayed in study B. FINDINGS: The
      systemic thiamine exposure of the test compound was slightly greater than that of
      reference A, based on the geometric mean ratio (%) of the AUClast value for
      plasma (116.6%) and hemolysate (137.5%). The thiamine diphosphate (TDP)
      distribution between plasma and hemolysate showed clear differences according to
      the formulations, in that more TDP was present in the hemolysate when thiamine
      was given as the test formulation. The AUClast value of plasma thiamine showed a
      >300% increase when thiamine was given as the test formulation in study B. The
      summed total exposure to thiamine (thiamine + TDP in both plasma and hemolysate)
      observed as a point estimate after the administration of fursultiamine was
      slightly greater than that with benfotiamine; however, the 90% CI was within the
      conventional bioequivalence range. IMPLICATIONS: These findings support clear
      benefits of lipophilic thiamine derivatives in the absorption of thiamine in
      healthy volunteers. Clinical Research Information Service identifiers: KCT0001419
      (study A), KCT0001628 (study B).

PMID- 27707510
TI  - Publicly Available Outcome Data for Individual Surgeons: Lessons from Cardiac
      Surgery.
AB  - Surgeon-specific outcome data for cardiac surgery have been published in the UK
      since 2005 and have been associated with improvement in risk-adjusted survival
      over time. This reassurance about the safety of cardiac surgery is unique in the
      world, but it remains controversial.

PMID- 27707511
TI  - Scientific Misconduct: The Elephant in the Lab. A Response to Parker et al.

PMID- 27707512
TI  - Pulmonary Artery Catheter Placement Using Transesophageal Echocardiography.
AB  - OBJECTIVE: To assess the feasibility of pulmonary artery catheter placement using
      transesophageal echocardiography inclusive of a description of the technique.
      DESIGN: A prospective, proof-of-concept study. SETTING: Single university
      hospital. PARTICIPANTS: Twenty patients with chronic thromboembolic pulmonary
      hypertension scheduled for pulmonary thromboendarterectomy. INTERVENTIONS:
      Pulmonary artery catheters were placed in 20 patients solely by transesophageal
      echocardiographic guidance. MEASUREMENTS AND MAIN RESULTS: Placement of the
      pulmonary artery catheter in the pulmonary artery with transesophageal
      echocardiography guidance in fewer than 10 minutes was considered successful
      placement. The time to placement was measured from advancement of the pulmonary
      artery catheter in the superior vena cava (20 cm) to a final location at the
      junction of the right pulmonary artery and main pulmonary artery. All 20
      pulmonary artery catheters were placed successfully using transesophageal
      echocardiography guidance and the median time to placement was 43 seconds. In 9
      of the 20 patients (45%), the catheter was placed successfully on the first
      attempt without any adjustments. However, in 9 others (45%), the catheter
      required manipulation under transesophageal echocardiography vision. In 3
      patients (15%), the pulmonary artery catheter was observed to be coiled in the
      right atrium and in 1 instance (5%) manipulation of the catheter in the right
      ventricle was required to enter the outflow tract. CONCLUSIONS: Transesophageal
      echocardiography is a viable adjunctive method to conventional pressure waveform
      placement of pulmonary artery catheters in potentially difficult patients.

PMID- 27707513
TI  - B-1 cell decreases susceptibility to encephalitozoonosis in mice.
AB  - Encephalitozoon cuniculi is an opportunist intracellular pathogen of mammals. The
      adaptive immune response is essential to eliminate E. cuniculi, but evidence is
      mounting that the response initiated by the innate immune response may ultimately
      define whether or not the parasite can survive. B-1 cells may act as antigen
      presenting cells or differentiate into phagocytes, playing different roles in
      many infection models. However, the role of these cells in the dynamics of
      Encephalitozoon sp. infections is still unknown. To investigate the role of B-1
      cells in E. cuniculi infection, BALB/c and BALB/c XID (B-1 cells deficient) mice
      were infected with E. cuniculi spores. Cytometric analyses of peritoneal cells
      showed that B-1 cells and macrophages increased significantly in infected BALB/c
      mice compared to uninfected controls. Despite the increase in the number of CD4+
      and CD8+ lymphocytes in XID mice, these animals were more susceptible to
      infection as evidenced histologically with more prominent inflammatory lesions
      and parasite burden. Pro-inflammatory cytokines increased in both infected BALB/c
      and BALB/c XID mice. To confirm B-1 cells role in encephalitozoonosis, we
      adoptively transferred B-1 cells to BALB/c XID mice and this group showed few
      symptoms and microscopic lesions, associated with an increased in cytokines.
      Together, these results suggest that B-1 cells may increase the resistance of
      BALB/c mice to encephalitozoonosis, evidencing for the first time the important
      role of B-1 lymphocytes in the control of microsporidia infection.

PMID- 27707514
TI  - Non-redundant role of the chemokine receptor CX3CR1 in the anti-inflammatory
      function of gut macrophages.
AB  - Mucosal immunity at the intestinal level is constantly challenged by the presence
      of external food and microbial antigens and must be kept under strict control to
      avoid the rise of aberrant inflammation. Among cells of the innate immunity,
      macrophages expressing the chemokine receptor CX3CR1 are strategically located
      near the gut epithelial barrier. These cells contribute to the maintenance of
      homeostasis by producing the anti-inflammatory cytokine IL-10; however, their
      role in the control of full blown inflammation and tissue injury is
      controversial. In this study we investigated mice proficient or deficient for the
      expression of the CX3CR1 receptor in a model of dextran sulphate sodium (DSS)
      induced acute colitis. We found that KO mice (CX3CR1GFP/GFP) had a more severe
      disease compared to WT mice (CX3CR1GFP/+), both in terms of histological
      examination of colonic tissues and leukocyte infiltration, with an expansion of
      macrophages and CD4-Th17 lymphocytes. The expression of several inflammatory
      mediators (IL-1beta, IL-6, IFNgamma, iNOS) was also significantly upregulated in
      KO mice, despite higher IL-10 production. Overall, our study demonstrates that
      macrophages expressing a functional CX3CR1 receptor have an important and non
      redundant role in controlling the abnormal intestinal inflammation that may lead
      to tissue damage.

PMID- 27707515
TI  - Families Matter: Social Support and Mental Health Trajectories Among Lesbian,
      Gay, Bisexual, and Transgender Youth.
AB  - PURPOSE: Lesbian, gay, bisexual, and transgender (LGBT) adolescents are at
      greater risk for mental health problems than their heterosexual peers, in part
      due to victimization. Social support, particularly from families, has been
      identified as an important promotive factor. However, little is known about how
      LGBT youth experience multiple forms of support or how early support predicts
      mental health across adolescence and into young adulthood. METHODS: In an
      analytic sample of 232 LGBT youth aged 16-20 years at baseline across 5.5 years,
      we compared developmental trajectories of psychological distress between three
      empirically derived social support cluster types at baseline: those who reported
      uniformly low support, those who reported uniformly high support, and those who
      reported nonfamily support (i.e., high peer and significant other but low family
      support). RESULTS: Longitudinal multilevel modeling, controlling for age,
      victimization, and social support at each wave, indicated key differences between
      cluster types. Youth in the low and nonfamily support clusters reported greater
      distress across all time points relative to youth in the high support cluster;
      however, they also showed a sharper decline in distress. Youth in the nonfamily
      cluster gained family support across adolescence, such that they resembled youth
      in the high support cluster by early adulthood. CONCLUSIONS: Findings underscore
      the importance of family support for LGBT youth. Youth who lack family support,
      but who have other forms of support, report a decrease in psychological distress
      and an increase in family support across adolescence. Youth who are low in all
      forms of support continue to exhibit high distress.

PMID- 27707517
TI  - [Elderly people with inappropriate prescriptions; should we de-prescribe?]

PMID- 27707516
TI  - Tobacco Marketing Receptivity and Other Tobacco Product Use Among Young Adult Bar
      Patrons.
AB  - PURPOSE: Use of other tobacco products (smokeless tobacco, hookah, cigarillo, and
      e-cigarettes) is increasing, particularly among young adults, and there are few
      regulations on marketing for these products. We examined the associations between
      tobacco marketing receptivity and other tobacco product (OTP) use among young
      adult bar patrons (aged 18-26 years). METHODS: Time-location sampling was used to
      collect cross-sectional surveys from 7,540 young adult bar patrons from January
      2012 through March of 2014. Multivariable logistic regression analyses in 2015
      examined if tobacco marketing receptivity was associated (1) with current (past
      30 day) OTP use controlling for demographic factors and (2) with dual/poly use
      among current cigarette smokers (n = 3,045), controlling for demographics and
      nicotine dependence. RESULTS: Among the entire sample of young adult bar patrons
      (Meanage = 23.7, standard deviation = 1.8; 48.1% female), marketing receptivity
      was consistently associated with current use of all OTP including smokeless
      tobacco (adjusted odds ratio [AOR]= 2.56, 95% confidence interval [CI] 2.08-3.16,
      p < .001), hookah (AOR = 1.97, 95% CI 1.58-2.43, p < .001), cigarillos (AOR =
      3.00, 95% CI 2.21-4.08, p < .001), electronic cigarettes (AOR = 2.43, 95% CI 1.93
      3.04, p < .001), and multiple tobacco products (AOR = 2.93, 95% CI 2.45-3.51, p <
      .001). Among current smokers, marketing receptivity was significantly associated
      with use of smokeless tobacco (AOR = 1.63, 95% CI 1.22-2.18, p < .01), cigarillos
      (AOR = 1.81, 95% CI 1.22-2.70, p < .01), and multiple tobacco products (AOR =
      1.58, 95% CI 1.27-1.97, p < .001). CONCLUSIONS: OTP use is common among young
      adult bar patrons, and it is associated with tobacco marketing receptivity.
      Efforts to limit tobacco marketing should address OTP in addition to cigarettes.

PMID- 27707519
TI  - Authors' response to comments on "Evaluation of one-step luminescent
      cyanoacrylate fuming".

PMID- 27707518
TI  - [Care costs and activity in the last three months of life of cancer patients who
      died in the Basque Country (Spain)].
AB  - OBJECTIVE: To analyse the use of health resources and its budget in the last
      months of life of the population who died from malignant neoplasm in the Basque
      Autonomous Country (Spain). METHOD: Retrospective observational study of a
      population with a diagnosis of malignancy deceased in the Basque Country (2010
      and 2011). DATA SOURCE: MDS and Mortality Register. VARIABLES: gender, age, place
      of death, tumour location, clinical activity data and costs in the last three
      months of life. We performed a descriptive analysis of clinical activity and
      costs, and lineal multivariate regressions to obtain the adjusted mean costs by
      gender, age and place of death. RESULTS: 9,333 deaths from malignancy were
      identified in 2010 and 2011. 65.4% were men, 61.5% aged 70 or over, mean age 72.9
      years, 71.1% died in hospital. People who died in the hospital had an average
      cost of about double that of the people who died at home (?14,794 and ?7,491,
      respectively; p <0.001) and 31.3% higher than in the nursing home (?11,269; p
      <0.001). CONCLUSIONS: Greater interventions at the end of life at the community
      level are necessary, strengthening the care capacity of primary health care, both
      from training and support from expert teams in order to change the current care
      profile to a more outpatient care that allows a lower consumption of resources
      and greater care at home.

PMID- 27707520
TI  - Molecular characterization of methoprene-tolerant gene (Met) in the swimming crab
      Portunus trituberculatus: Its putative role in methyl farnesoate-mediated
      vitellogenin transcriptional activation.
AB  - Methoprene-tolerant (Met) belongs to the basic helix-loop-helix (bHLH)-Per-Arnt
      Sim (PAS) family of nuclear transcriptional regulators, and is the leading
      candidate receptor for the insect Juvenile hormone (JH) and the crustacean methyl
      farnesoate (MF). In the present study, a full-length cDNA of Met was cloned from
      the swimming crab, Portunus trituberculatus (PtMet). The PtMet amino acid
      sequence was found to contain domains characteristic of the bHLH-PAS family
      proteins and to have several conserved amino acid residues specifically
      responsible for JH or MF binding. In addition to its extensive tissue expression,
      PtMet mRNA is highly expressed in the female hepatopancreas, the primary site of
      vitellogenin (Vg) synthesis in P. trituberculatus. PtMet expression was
      significantly increased in the early-vitellogenic stage of ovarian development,
      which indicated that likely involvement in vitellogenesis regulation. In vitro,
      MF induced up-regulation of PtMet and PtVg expression in the hepatopancreas, but
      not in the ovary. In vivo, MF induced PtMet and PtVg expression in the
      hepatopancreas,and only PtMet expression was induced in the ovary. Taken
      together, these results suggest that Met can potentially serve as a MF receptor
      in crustaceans. In addition, the binding of Met to MF might transcriptionally
      regulate Vg synthesis in the hepatopancreas.

PMID- 27707521
TI  - Use of heterospermic inseminations and paternity testing to evaluate the relative
      contributions of common sperm traits and seminal plasma proteins in boar
      fertility.
AB  - The objective of this study was to evaluate relationships between common semen
      quality estimates including sperm motility, sperm morphology, spontaneous
      capacitation status and seminal plasma proteins and boar fertility using
      heterospermic inseminations and subsequent paternity testing. All boars (n=12)
      used in the study had excellent semen quality (>=70% normal sperm) that resulted
      in average farrowing rates and litter sizes of 88.9+/-0.7% and 11.7+/-0.1 pigs,
      respectively. Their ejaculates were combined to make heterospermic insemination
      doses in such a way that each boar was tested against all of his contemporaries.
      The proportion of piglets sired by each individual was used to separate boars
      into three fertility groups: High (71.6+/-4.8%; n=3); Medium (51.6+/-3.8%; n=6);
      and Low (25.2%+/-5.3%; n=3). Ejaculates from High fertility boars had more motile
      sperm with normal acrosomes that moved faster in a straight-line and were more
      likely to undergo an acrosome reaction (p<=0.05) compared with their counterparts
      in the Low fertility group. Ejaculates from High fertility boars contained the
      greatest concentrations of three seminal plasma proteins (25.9kD/5.9pI;
      55.1kD/4.8pI; and 70.1kD/5.2pI; p<=0.05), whereas concentrations of a
      19.1kD/6.8pI were highest in semen from Low fertility boars (p<=0.05). Multiple
      regression analyses indicated that concentrations of the 25.9kD/5.9pI seminal
      plasma protein explained 66% of the variation observed in the proportion of pigs
      sired within a litter among boars (p<=0.00001). These results demonstrate that
      heterospermic inseminations and subsequent paternity testing is an effective
      technique for defining relationships between common semen quality tests and
      fertility, especially in situations where reproductive performance of all the
      boars is high. Motility, normal acrosome morphology, average linear velocity of
      motile sperm, and the proportion of sperm capable of an acrosome reaction were
      all positively associated with boar fertility. However, concentrations of a
      25.9kD/5.9pI seminal plasma protein were the best single semen characteristic for
      ranking boars in terms of their fertility.

PMID- 27707523
TI  - Influence of morphine treatment on in-hospital mortality among patients with
      acute heart failure.

PMID- 27707524
TI  - Secondary depression in transdiagnostic group cognitive behavioral therapy among
      individuals diagnosed with anxiety disorders.
AB  - Anxiety and depression co-occur at high rates, and their comorbidity typically
      creates a more severe clinical presentation then either alone. The effect of
      comorbid depression appears to vary across anxiety and related disorders.
      Transdiagnostic treatments present a promising option to improve comorbid
      conditions by targeting shared factors (e.g., information processing biases). The
      purpose of this study was to examine the reciprocal effects of secondary
      depression in transdiagnostic group cognitive behavioral therapy for anxiety
      (TGCBT). 120 individuals diagnosed with a primary anxiety disorder, 42 of whom
      had a depressive diagnosis, were enrolled in 12 weeks of TGCBT. Depressed
      individuals were compared to those without a depressive diagnosis on both
      clinician-rated and self-reported anxiety and depression following TGCBT.
      Although depressed individuals scored higher on most indices of anxiety at pre
      treatment, both groups improved similarly with some evidence of greater
      improvement among those with comorbid depression. All individuals improved in
      self-reported depressive symptoms and comorbid depression improved to subclinical
      levels. These results posit TGCBT as an effective, efficient option for treating
      patients with anxiety and comorbid depression.

PMID- 27707525
TI  - Association of Pre-hospital ECG Administration With Clinical Outcomes in ST
      Segment Myocardial Infarction: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Delays in reperfusion for patients with myocardial ischemia leads to
      increased morbidity and mortality. The objective of this review was to identify,
      evaluate, and critically appraise the evidence on whether pre-hospital
      electrocardiography (ECG) reduces patient mortality and improves post-ST-segment
      myocardial infarction patient-oriented outcomes. METHODS: We searched
      PubMed/MEDLINE, EMBASE, and Cochrane Library (1990-2015) for controlled clinical
      studies. We also searched conference proceedings, trial registries, and reference
      lists of narrative and systematic reviews. Two reviewers independently identified
      and extracted data from studies that compared pre-hospital ECG with standard of
      care in patients with suspected myocardial infarction who underwent primary
      percutaneous coronary intervention. Internal validity was assessed using the
      Newcastle-Ottawa scale. RESULTS: We screened 21,197 citations and included 63
      unique studies (plus 22 companion publications). Most studies were of moderate
      quality. Pre-hospital ECG was associated with significantly fewer deaths
      (relative risk, 0.68; 95% confidence interval [CI], 0.63-0.74; 45 studies; 71,315
      patients; I2, 0%), reduced time to reperfusion (mean difference, -35.32 minutes;
      95% CI, -44.02 to -26.61; 26 studies; 27,524 patients; I2, 97%), shorter hospital
      stays (mean difference, -0.63 days; 95% CI, -1.05 to -0.20; 10 studies; 39,275
      patients; I2, 39%), and more patients had first medical contact to device time <
      90 minutes than standard of care (relative risk, 1.77; 95% CI, 1.52-2.07; 11
      studies; 20,991patients; I2, 93%). CONCLUSIONS: Use of pre-hospital ECG is
      associated with decreased mortality and overall better patient outcomes.

PMID- 27707522
TI  - Erythrocytes as Carriers for Drug Delivery in Blood Transfusion and Beyond.
AB  - Red blood cells (RBCs) are innate carriers that can also be engineered to improve
      the pharmacokinetics and pharmacodynamics of many drugs, particularly
      biotherapeutics. Successful loading of drugs, both internally and on the external
      surface of RBCs, has been demonstrated for many drugs including anti
      inflammatory, antimicrobial, and antithrombotic agents. Methods for internal
      loading of drugs within RBCs are now entering clinical use. Although internal
      loading can result in membrane disruption that may compromise biocompatibility,
      surface loading using either affinity or chemical ligands offers a diverse set of
      approaches for the production of RBC drug carriers. A wide range of surface
      determinants is potentially available for this approach, although there remains a
      need to characterize the effects of coupling agents to these surface proteins.
      Somewhat surprisingly, recent data also suggest that red cell-mediated delivery
      may confer tolerogenic immune effects. Questions remaining before widespread
      application of these technologies include determining the optimal loading
      protocol, source of RBCs, and production logistics, as well as addressing
      regulatory hurdles. Red blood cell drug carriers, after many decades of progress,
      are now poised to enter the clinic and broaden the potential application of RBCs
      in blood transfusion.

PMID- 27707526
TI  - Identifying and Managing Premature Ventricular Contraction-Induced
      Cardiomyopathy: What, Why, and How?
AB  - Premature ventricular contraction (PVC)-induced cardiomyopathy is increasingly
      being recognized as a reversible cause of left ventricular (LV) systolic
      dysfunction (LVSD). The diagnosis of PVC-induced cardiomyopathy is considered in
      subjects with high PVC burdens (> 10,000 per 24 hours) after excluding other
      known causes of LVSD. PVC suppression is the mainstay of the management of PVC
      induced cardiomyopathy, in addition to proven evidence-based medical therapy
      recommended for subjects with LVSD. Management strategies for PVC-induced
      cardiomyopathy include medical therapy and/or catheter ablation, with an
      increasing role for catheter ablation as a first-line therapy in view of the
      potential for permanent suppression of PVCs. Recovery of LVSD is typically a
      gradual process over months after effective suppression of PVCs. Last,
      asymptomatic patients with high PVC burdens and preserved LV systolic function
      appear to be at low risk over the intermediate term for developing LVSD. However,
      it is prudent to monitor LV function periodically because of the potential for
      deterioration of LV function observed during long-term follow-up in some
      subjects.

PMID- 27707527
TI  - Chemical agents for the sedation of agitated patients in the ED: a systematic
      review.
AB  - OBJECTIVE: Chemical agents commonly used to sedate agitated patients in the
      emergency department include benzodiazepines, antipsychotics, or a combination of
      the 2 classes. Our objective was to determine if a class or combination therapy
      is (1) more effective, as measured by the proportion sedated at 15-20 minutes and
      the need for repeat sedation, and (2) safer, as measured by the proportion of
      reported adverse events. METHODS: Systematic literature review and meta-analysis
      of studies comparing 2 or more chemical agents for sedation of agitated patients
      in the emergency department were carried out in PubMed, PsycINFO, Embase, and the
      Cochrane database. Meta-analyses for pairwise comparisons of drug class
      (benzodiazepine, antipsychotic, or combination) were carried out for each
      outcome: proportion sedated, need for repeat sedation, and adverse events.
      RESULTS: Seven studies with 1135 patients were included. At 15-20 minutes, the
      proportion of patients sedated was greater with combination therapy than
      benzodiazepines alone (risk ratio [RR] = 1.31, P < .0001). Antipsychotics and
      combination agents required significantly less repeat sedations than
      benzodiazepines alone (RR = 0.49, P < .0001 and RR = 0.64, P = .002). There was
      significant heterogeneity in adverse event data, with respiratory system adverse
      events (desaturation, and need for airway and ventilatory support) being the most
      commonly reported. Benzodiazepines were associated with a higher incidence of
      adverse events than antipsychotics or combination therapy. CONCLUSION:
      Combination therapy sedated a greater proportion of patients at 15-20 minutes
      than benzodiazepines alone. Antipsychotics and combination therapy were more
      effective, requiring less repeat doses for sedation than benzodiazepines. The
      risk of any adverse event was higher with benzodiazepines.

PMID- 27707528
TI  - Idarucizumab, a specific reversal agent for dabigatran: mode of action,
      pharmacokinetics and pharmacodynamics, and safety and efficacy in phase 1
      subjects.
AB  - The direct oral anticoagulants (DOACs) provide a number of clinical advantages
      over vitamin K antagonists for the treatment of thromboembolism, including
      improved efficacy and safety, as well as no need for regular monitoring of
      anticoagulant effect. However, as with all anticoagulants, bleeding complications
      may occur, and anticoagulant reversal may be required in specific clinical
      situations, such as in patients experiencing spontaneous or traumatic bleeds, or
      in anticoagulated patients requiring emergency surgery or other invasive
      procedures. Therefore, several reversal agents for the DOACs are in development.
      This includes the specific reversal agent idarucizumab, which has been approved
      by the U.S. Food and Drug Administration and the European Medicines Agency for
      use in patients treated with dabigatran when urgent reversal of its anticoagulant
      effects is needed. Idarucizumab is a humanized monoclonal antibody fragment that
      binds with high affinity to free and thrombin-bound dabigatran, resulting in an
      almost irreversibly bound idarucizumab-dabigatran complex and thereby
      neutralizing dabigatran's anticoagulant activity. The reversal of the
      anticoagulant effects of dabigatran by idarucizumab has been demonstrated in
      animal bleeding models, in healthy volunteers with a range of ages and renal
      function, and in anticoagulated patients. In the phase 1 trials, at doses of 2 g
      or greater, idarucizumab resulted in immediate and complete reversal of the
      dabigatran anticoagulant effects and was well tolerated. In the absence of
      dabigatran, idarucizumab showed no effect on coagulation parameters or thrombin
      formation. These findings provide initial evidence that idarucizumab could
      provide a safe and effective means of reversing anticoagulant activity in
      patients treated with dabigatran in need of emergency surgery or in emergency
      bleeding situations.

PMID- 27707529
TI  - Antineuronal Nuclear Autoantibody Type 1/Anti-Hu-Associated Opsoclonus Myoclonus
      and Epilepsia Partialis Continua: Case Report and Literature Review.
AB  - BACKGROUND: Opsoclonus-myoclonus syndrome is a rare clinical condition that has
      been associated with neuroblastoma. There are few reported examples of ANNA
      1/anti-Hu antibodies in children with neuroblastoma and opsoclonus-myoclonus, all
      in children aged less than three years of age. METHODS: We describe the new onset
      of focal seizures without alteration of consciousness and opsoclonus-myoclonus in
      an 11-year-old girl with ANNA-1/anti-Hu positivity and a paraspinal
      ganglioneuroblastoma. A systematic review of the literature of children with ANNA
      1/anti-Hu positivity and malignancy was also performed. RESULTS: Fourteen
      patients were identified, eight of whom had opsoclonus-myoclonus. Although
      epilepsia partialis continua has been described in association with several
      neuronal autoantibodies, association with ANNA-1/anti-Hu has not been reported.
      CONCLUSIONS: We describe epilepsia partialis continua in a child with ANNA-1/anti
      Hu antibodies and neuroblastoma. Testing for antineuronal antibodies should be
      considered in children presenting with either opsoclonus-myoclonus or epilepsia
      partialis continua.

PMID- 27707530
TI  - Effect of patient age on treatment response in a study of the acute exacerbation
      of psychosis in schizophrenia.
AB  - Younger patients with schizophrenia have most likely experienced fewer adverse
      consequences of the illness than older patients who may have experienced a
      lifetime of treatment as well as socio-economic problems as a consequence of the
      illness. There is limited information regarding differential efficacy of long
      acting injectable (LAI) antipsychotic medications across the age span in patients
      with schizophrenia. We conducted a post hoc age and gender analysis of treatment
      response to aripiprazole lauroxil (AL; ARISTADA(r); Alkermes, Inc.), in a 12
      week, double-blind, placebo-controlled, multinational, Phase 3 study evaluating
      two doses of AL (441mg and 882mg) versus placebo in adult patients experiencing
      an acute exacerbation of schizophrenia within the previous 2months. We examined
      change in the total Positive and Negative Syndrome Scale (PANSS) scores from
      baseline using analysis of covariance and categorical treatment response (defined
      as >=30% total PANSS score improvement from baseline) in the following age
      groups: <30, 30-39, 40-49, and 50-69years old. Age and gender did not moderate
      the treatment response in this study. Both AL 441mg and AL 882mg showed an early
      and significant improvement of the mean total PANSS scores and categorical
      treatment responses compared to placebo in all four age groups, including younger
      patients regardless of gender that was sustained over the 85-day treatment
      period.

PMID- 27707531
TI  - Suicidal behaviors in children and adolescents with psychotic disorders.
AB  - Suicide is the leading cause of premature death in individuals with psychotic
      disorders. Risk for onset of suicidal behaviors tends to begin in adolescence,
      remaining high into young adulthood. The present study aims to evaluate the
      interplay of early onset psychosis and suicide risk by examining suicidal
      behaviors (ideation, planning, and attempts) in children and adolescents with
      psychotic disorders (PD) compared to typically developing peers (TD). Twenty five
      youths were recruited and were diagnostically evaluated for psychosis. We found
      that the PD children exhibited significantly higher levels of suicidal behaviors
      than TD children, even when parsed into individual at-risk behaviors.

PMID- 27707532
TI  - [Perspective of intensive care nursing staff on the limitation of life support
      treatment].
AB  - OBJECTIVE: To determine the perspective of intensive care nursing staff on the
      limitation of life support treatment (LLST) in the Intensive Care Units. METHOD:
      An exploratory qualitative study was carried out by applying the theory of
      Strauss and Corbin as the analysis tool. Constructivist paradigm. POPULATION:
      Nursing staff from three Intensive Care Units of Hospital Universitari de
      Bellvitge. Convenience sampling to reach theoretical saturation of data. Data
      collection through semi-structured interview recorded prior to informed consent.
      Rigor and quality criteria (reliability, credibility, transferability), and
      authenticity criteria: reflexivity. Demographic data was analysed using Excel.
      RESULTS: A total of 28 interviews were conducted. The mean age of the nurses was
      35.6 years, with a mean seniority of 11.46 years of working in ICU. A minority of
      nurses (21.46%) had received basic training in bioethics. The large majority
      (85.7%) believe that LLST is not a common practice due to therapeutic cruelty and
      poor management with it. There is a correlation with the technical concepts; but
      among the main ethical problems is the decision to apply LLST. Nurses recognise
      that the decision on applying LLST depends on medical consensus with relatives,
      and they believe that their opinion is not considered. Their objective is trying
      to avoid suffering, and assist in providing a dignified death and support to
      relatives. CONCLUSIONS: There is still a paternalistic pattern between the doctor
      and patient relationship, where the doctor makes the decision and then agrees
      with the relatives to apply LLST. Organ failure and poor prognosis are the most
      important criteria for applying LLST. It is necessary to develop a guide for
      applying LLST, emphasising the involvement of nurses, patients, and their
      relatives.

PMID- 27707534
TI  - Corrigendum to "Chronic hepatitis B: immune pathogenesis and emerging
      immunotherapeutics" [Curr. Opin. Pharmacol. 30 (2016) 93-105].

PMID- 27707533
TI  - Spike on T wave! What went wrong?
AB  - An 80-year-old male, who previously received a dual chamber pacemaker, was
      referred to our ambulatory for dizziness and fatigue. The ECG obtained showed
      sinus rhythm, highly variable atrioventricular (AV) interval and alternation
      between spontaneous and paced ventricular complexes. A spike on the ascending
      part of the T wave was observed, suggesting ventricular undersensing. However,
      telemetry-supported pacemaker control showed inconstant atrial undersensing.

PMID- 27707535
TI  - Network analysis of the Quick Inventory of Depressive Symptomatology: Reanalysis
      of the STAR*D clinical trial.
AB  - Network analysis is yet to be used to examine patient-reported symptom severity
      and change during citalopram treatment for major depressive disorder. We aimed to
      identify: (I) network systems; (II) central symptoms; and (III) network
      differences, in patient-reported depression for baseline, endpoint and change
      scores. STAR*D data during citalopram treatment were reanalyzed to examine
      depression based on the Quick Inventory of Depressive Symptomatology Self-Report
      (QIDS-SR). Network analyses were computed from the QIDS-SR item-level severity
      scores at baseline and endpoint, and from estimated change scores based on mixed
      models, adjusted for confounding by dose and baseline severity. Centrality
      indices for each symptom were computed. Networks were contrasted for connectivity
      with permutation tests. Network analyses grouped symptoms consistently as: Sleep
      disturbances, cognitive and physical avolition, Affect and Appetite. Symptom
      centrality was highest for Energy at baseline, Mood at endpoint, and Mood and
      Concentration on change scores. Generally, permutation tests showed that the
      networks all significantly (p<.05) differed. Results demonstrated: (I) a
      replicable network group of the symptoms of depression that modestly mapped onto
      well-known mechanisms for depression; (II) symptoms with high centrality that may
      be future treatment targets (e.g., mood); and (III) that the form of the networks
      differed across treatment time-points, thereby contributing centrality as a
      possible mechanism to the initial severity debate. These findings highlight the
      utility of focusing on symptoms rather than total scores to understand how
      treatment unfolds, and tentative mechanisms.

PMID- 27707536
TI  - Interpreting change on the SCAT3 in professional ice hockey players.
AB  - OBJECTIVES: To examine test-retest reliability of the SCAT3 for two consecutive
      seasons using a large sample of professional male ice hockey players, and to make
      recommendations for interpreting change on the test. DESIGN: A cross-sectional
      descriptive study. METHODS: Preseason baseline testing was administered in the
      beginning of the seasons 2013-2014 and 2014-2015 to 179 professional male hockey
      players in rink side settings. RESULTS: The test-retest reliabilities of the
      SCAT3 components were uniformly low. However, the majority of athletes remained
      grossly within their own individual performance range when two pre-season SCAT3
      baseline scores were compared to published normative reference values. Being
      tested by the same person or a different person did not influence the results. It
      was uncommon for the Symptom score to worsen by >=3 points, the Symptom Severity
      score to worsen by >=5 points, SAC total score to worsen by >=3 points, M-BESS
      total error points to increase by >=3, or the time to complete Tandem Gait to
      increase by >=4s; each occurred in less than 10% of the sample. CONCLUSIONS: The
      SCAT3 has low test-retest reliability. Change scores should be interpreted with
      caution, and more research is needed to determine the clinical usefulness of the
      SCAT3 for diagnosing concussion and monitoring recovery. Careful examination of
      the natural distributions of difference scores provides clinicians with useful
      information on how to interpret change on the test.

PMID- 27707537
TI  - Exercise in patients with hypertrophic cardiomyopathy: A review of current
      evidence, national guideline recommendations and a proposal for a new direction
      to fitness.
AB  - Hypertrophic cardiomyopathy is a common genetic disorder with a prevalence of
      1:500 in the general population. Amongst a varied spectrum of clinical
      presentations, the most feared complication of this cardiac disorder is sudden
      cardiac death. Although only a minority of patients with hypertrophic
      cardiomyopathy who suffer sudden cardiac death or resuscitated cardiac arrest do
      so during exercise, strenuous physical activity is regarded as an important
      trigger for these tragic outcomes. Furthermore, during exercise, patients with
      hypertrophic cardiomyopathy may develop augmentation of left ventricular outflow
      tract obstruction, myocardial ischemia, diastolic dysfunction and/or
      inappropriate vasodilation in non-exercising vascular beds. This in turn may lead
      to exertional dyspnea, chest pain or syncope. Accordingly, patients with
      hypertrophic cardiomyopathy are disqualified from competitive sports and in many
      cases are recommended to avoid strenuous physical activity of any kind.
      Nevertheless, avoidance of physical activity comes with a price. The positive
      effects of regular exercise have been extensively reported to convey a wide range
      of benefits including reduced cardiovascular events, weight reduction and
      improved wellbeing. Therefore, finding the right exercise level that will offer
      some of the benefits of physical activity without increasing the risk of sudden
      cardiac death is of utmost importance. In this review, we discuss the current
      evidence for and against exercise in this patient population and review national
      guideline recommendations. We also propose alternative fitness strategies
      including a novel fitness program implemented by our hypertrophic cardiomyopathy
      center which may be of particular usefulness for hypertrophic cardiomyopathy
      patients.

PMID- 27707538
TI  - Diffuse Hepatic Hemangiomatosis of rapid growth after Bariatric Surgery.

PMID- 27707539
TI  - Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF
      patient homozygous for the W1282X CFTR nonsense mutation.
AB  - Premature termination codons (PTCs) in cystic fibrosis transmembrane conductance
      regulator (CFTR) gene result in nonfunctional CFTR protein and are the proximate
      cause of ~11% of CF causing alleles. Aminoglycosides and other novel agents are
      known to induce translational readthrough of PTCs, a potential therapeutic
      approach. Among PTCs, W1282X CFTR is unique, as it is a C-terminal CFTR mutation
      that can exhibit partial activity, even in the truncated state. The potentiator
      ivacaftor (VX-770) is approved for treating CF patients with G551D and other
      gating mutations. Based on previous studies demonstrating the beneficial effect
      of ivacaftor for PTC mutations following readthrough in vitro, we hypothesized
      that ivacaftor may enhance CFTR activity in CF patients expressing W1282X CFTR,
      and could be further enhanced by readthrough. Ivacaftor significantly increased
      CFTR activity in W1282X-expressing cells compared to R1162X CFTR cells, and was
      further enhanced by readthrough with the aminoglycoside G418. Primary nasal
      epithelial cells from a W1282X homozygous patient showed improved CFTR function
      in the presence of ivacaftor. Upon ivacaftor administration to the same patient,
      there was significant improvement in pulmonary exacerbation frequency, BMI, and
      insulin requirement, whereas FEV1 remained stable over 3years. These studies
      suggest that ivacaftor may have moderate clinical benefit in patients with
      preserved expression of the W1282X CFTR mutation by stimulating residual activity
      of the truncated protein, suggesting the need for further studies including the
      addition of efficacious readthrough agents.

PMID- 27707540
TI  - Evidence to inform the future for maternal and newborn health.
AB  - Despite the impressive progress gains for maternal and child health during the
      Millennium Development Goals era, over 5.6 million women and babies died in 2015
      due to complications during pregnancy, birth and in the first month of life. In
      order to achieve the new mortality targets set out in the Sustainable Development
      Goals, there needs to be intentional efforts to maintain and accelerate action to
      end preventable maternal and newborn deaths and stillbirths. This paper outlines
      what progress is required to meet these new 2030 targets based on patterns of
      progress in the recent past; where the burden is the greatest; when to focus
      attention along the continuum of care; and what causes of death require concerted
      efforts. Priority actions include intentional and intensified political attention
      and investment in maternal-newborn health with particular focus on improving
      quality and experience of care around the time of birth with implementation at
      scale of integrated maternal-newborn health interventions across the continuum of
      care with commensurate investment targeted at the most vulnerable populations.
      Looking forward, improved data for decision making and accountability will be
      required. The health and survival of babies and their mothers are inextricably
      linked, and calls for coordinated efforts and innovation before and during
      pregnancy, in childbirth, and postnatally, in order to end preventable maternal,
      neonatal deaths and stillbirths.

PMID- 27707541
TI  - Association and multiple interaction analysis among five XRCC1 polymorphic
      variants in modulating lung cancer risk in North Indian population.
AB  - XRCC1 is a scaffold protein that provides for interaction of DNA polymerase, DNA
      ligase and damaged DNA. Genotyping was done for the five non-synonymous and
      synonymous variants of XRCC1 i.e. XRCC1, Arg194Trp, Pro206Pro, Arg280His,
      Arg399Gln, Gln632Gln. Logistic regression analysis was used to analyze the
      association of XRCC1 with lung cancer, followed by data mining analysis which
      included both Multi-dimensionality reduction (MDR) and Classification and
      Regression tree (CART) analysis so as to find possible interaction between SNPs
      on XRCC1 gene. Statistical analysis revealed XRCC1 Gln632Gln (OR=2.67, p=<0.001)
      depicted an overall high risk towards lung cancer. Histological subdivision
      revealed carriers of mutant genotype in case of XRCC1 Arg399Gln imposed a
      protective effect towards SQCC subtype. Likewise, mutant genotype in XRCC1
      Pro206Pro implied a protective effect for SCLC subtype (OR=0.29, p=0.0017) on the
      contrary XRCC1 Gln632Gln showed a high risk in SQCC diseased group (OR=4.16,
      p=<0.0001). Combination of XRCC1 Gln632Gln with other SNPs revealed XRCC1
      Gln632Gln with Arg194Trp (OR=2.10, p=0.03) and Pro206Pro (OR=5.6, p<0.0004)
      increased an overall risk towards lung cancer. Haplotype analysis illustrated
      haplotype block 11 (CGAGG) carrying minor allele for XRCC1 206 was associated
      with the highest risk towards lung cancer on the contrary block 4 (CAGAG)
      carrying mutant allele for XRCC1 399 significantly decreased the risk. Multi
      dimensionality reduction (MDR) results showed the three factor model comprising
      XRCC1 206, 632, 280 as the best model (CVC=10, prediction error=0.34). Further
      Classification and Regression tree (CART) analysis revealed terminal node 1
      carrying mutant of XRCC1 632 and wild type of XRCC1 280 represented the highest
      risk group. Our results demonstrated high order interaction between SNPs of XRCC1
      gene. This study depicted a positive association of XRCC1 Gln632Gln towards lung
      cancer, however XRCC1 Arg399Gln, Arg194Trp showed an overall no effect or
      protective effect.

PMID- 27707542
TI  - The Pol30-K196 residue plays a critical role in budding yeast DNA postreplication
      repair through interaction with Rad18.
AB  - PCNA plays critical roles in DNA replication and various DNA repair pathways
      including DNA damage tolerance (DDT). In budding yeast Saccharomyces cerevisiae,
      DDT (aka DNA postreplication repair, PRR) is achieved by sequential
      ubiquitination of PCNA encoded by POL30. Our previous studies revealed that two
      Arabidopsis PCNA genes were able to complement the essential function of POL30 in
      budding yeast, but failed to rescue the PRR activity. Here we hypothesize that a
      certain amino acid variation(s) is responsible for the difference, and identified
      K196 as a critical residue for the PRR activity. It was found that the pol30
      K196V mutation abolishes Rad18 interaction and PRR activity, whereas nearby amino
      acid substitutions can partially restore Rad18 interaction and PRR activity.
      Together with the Pol30-Ub fusion data, we believe that we have identified a
      putative Rad18-binding pocket in Pol30 that is required for PCNA
      monoubiquitination and PRR.

PMID- 27707543
TI  - Effect of pH on ethanol-type acidogenic fermentation of fruit and vegetable
      waste.
AB  - The aim of this study was to investigate the possibility and optimal controlling
      strategy for ethanol-type acidogenic fermentation of fruit and vegetable waste by
      mixed microbial cultures. Four continuous stirred tank reactors (CSTR) were
      operated at various pHs (4.0, 5.0, 5.5, and 6.0) with an organic loading rate of
      13gVS/(Ld) and hydraulic retention time of 3d. Butyrate-type fermentation was
      observed at pH 5.0, 5.5, and 6.0. Conversely, at pH 4.0, ethanol-type
      fermentation was observed with a high mass concentration and proportion (of total
      fermentative products) of ethanol, which were 6.7g/L and 88.8%, respectively.
      However, the total concentration of ethanol-type fermentative products
      substantially decreased from days 22-25. The optimal pH of ethanol-type
      fermentative microorganisms was investigated by using batch experiments with pH
      controlled at 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, and 7.0 and results showed that the
      maximum ethanol concentration and relatively highest acidogenic rate were found
      at pH of 5.5. The pH in the long term CSTR was changed from 4.0 to 5.5 to improve
      ethanol-type fermentation and results showed that ethanol-type fermentation was
      improved temporarily, however, was followed by the reappearance of butyrate-type
      fermentation. In addition, ethanol-type fermentation recovered once more when pH
      was reverted to 4.0. Therefore, the results of this study suggest that a process
      of dynamic, sequenced pH control with the order pH 4.0, 5.5 and 4.0 might be a
      feasible controlling strategy for continuous and stable ethanol-type
      fermentation.

PMID- 27707544
TI  - Mealtime Structure and Responsive Feeding Practices Are Associated With Less Food
      Fussiness and More Food Enjoyment in Children.
AB  - OBJECTIVE: To identify associations between structure-related and non-responsive
      feeding practices and children's eating behaviors. DESIGN: Cross-sectional online
      survey design. PARTICIPANTS: Parents (n = 413) of 1- to 10-year-old children.
      MAIN OUTCOME MEASURES: Parental feeding practices and child eating behaviors were
      measured via the validated Feeding Practices and Structure and Children's Eating
      Behaviour questionnaires. ANALYSIS: Associations between parental feeding
      practices and children's eating behaviors were tested using hierarchical
      multivariable linear regression models, adjusted for covariates. RESULTS: Feeding
      practices accounted for 28% and 21% of the variance in food fussiness and
      enjoyment of food, respectively (P < .001). For all other eating behaviors the
      amount of variance explained by feeding practices was < 10% (P < .001). Key
      findings were that more structure and less non-responsive practices were
      associated with lower food fussiness and higher enjoyment of food. CONCLUSIONS
      AND IMPLICATIONS: Overall, the findings suggested that mealtime structure and
      responsive feeding are associated with more desirable eating behaviors. Contrary
      to predictions, there was no evidence to indicate that these practices are
      associated with better self-regulation of energy intake. Longitudinal research
      and intervention studies are needed to confirm the importance of these feeding
      practices for children's eating behaviors and weight outcomes.

PMID- 27707545
TI  - Surgical embryo collection but not nonsurgical embryo transfer compromises
      postintervention prolificacy in sows.
AB  - Recent advances in nonsurgical deep uterine (NsDU) embryo transfer (ET)
      technology allow the noninvasive transfer of porcine embryos into recipients,
      overcoming the most important impediment for commercial ET in this species.
      Although many factors in the porcine ET-field have been recently evaluated, many
      others remain to be explored. We investigated here the future reproductive
      performance of donors and recipients after artificial insemination subsequent to
      the default surgical embryo recovery approach and to the NsDU-ET procedure,
      respectively. Although surgical embryo collection did not influence subsequent
      farrowing rates (90.5%), litter size decreased severely (8.9 +/- 0.8 piglets)
      compared to presurgery (10.8 +/- 0.3 piglets) and control group (10.7 +/- 0.3
      piglets). In contrast, NsDU-ETs did neither affect fertility nor prolificacy of
      recipients in the cycle subsequent to ET, regardless of whether they were
      pregnant after NsDU-ET or not. These results indicate that while the surgical
      embryo collection procedure compromises the reproductive future of donor sows,
      the NsDU-ET approach does not affect the reproductive potential of the recipients
      after reintroduction to the breeding stock of the farm. Further research is thus
      needed to improve surgical embryo collection.

PMID- 27707547
TI  - Continuous contact with females in estrus throughout the year enhances testicular
      activity and improves seminal traits of male goats.
AB  - The "female effect" consists in the stimulation of males' reproductive activity
      by different signals emitted by females. This stimulation leads to endocrine and
      behavioral changes that may modify the seasonal pattern of male ruminants. The
      aims of this experiment were (1) to describe the local reproductive seasonal
      pattern of Gabon bucks and (2) to determine if continuous chemical, auditory, and
      visual contact with does in estrus enhances bucks' testicular activity and
      improves seminal traits throughout the year and modify their seasonal pattern. We
      used 16 adult Gabon bucks assigned to two experimental groups: nine bucks
      remained continuously isolated from females (isolated bucks, group IB) and seven
      bucks were in continuous chemical, auditory, and visual contact through a fence
      line with does in estrus (stimulated bucks, group SB). During 13 months, scrotal
      circumference and testosterone concentration were measured weekly and testicular
      echogenicity was measured every 2 weeks. Also, sperm motility mass and percentage
      of abnormal spermatozoa were determined, and sperm concentration and total number
      of motile spermatozoa were calculated every 2 weeks. Testicular echogenicity was
      greater in IB than that in SB bucks (P < 0.0001), but there were no differences
      in scrotal circumference. Overall, testosterone concentration was greater in IB
      than that in SB bucks (P = 0.04), but from late winter to mid-summer, when
      testosterone concentration presented basal concentrations, SB bucks had greater
      values than IB bucks (P = 0.004). Sperm concentration (P = 0.05) and sperm mass
      motility (P = 0.01) were greater in SB than that in IB bucks, and the total
      number of progressive motile spermatozoa tended to be greater in SB than in that
      IB bucks (P = 0.1). The percentage of abnormal spermatozoa was lower in SB than
      in IB bucks in several time points (P < 0.0001). Testicular and seminal traits
      were better from the end of the spring until mid-autumn. We concluded that does
      in estrus stimulated bucks' testicular activity, including better seminal quality
      and a greater increase of testicular fluid content than bucks isolated from
      females. However, the general seasonal pattern was not modified by stimulation
      with does in estrus.

PMID- 27707546
TI  - Split-time artificial insemination in beef cattle: II. Comparing pregnancy rates
      among nonestrous heifers based on administration of GnRH at AI.
AB  - This experiment was designed to evaluate split-time artificial insemination (AI)
      in beef heifers following administration of the 14-day controlled internal drug
      release (CIDR)-prostaglandin F2alpha (PG) protocol and to compare pregnancy rates
      among nonestrous heifers based on administration of GnRH at AI. Estrus was
      synchronized for 1138 heifers across six locations. Heifers received a CIDR
      insert (1.38 g progesterone) on Day 0 with removal on Day 14. Estrus detection
      aids (Estrotect) were applied at PG (25 mg), 16 days after CIDR removal on Day
      30. Heifers were assigned to balanced treatments based on reproductive tract
      score and weight, and treatments were represented within each location. Split
      time AI was performed at 66 and 90 hours after PG, and estrus was recorded at
      these times. Heifers in both treatments that exhibited estrus by 66 hours were
      inseminated and did not receive GnRH, whereas AI was delayed 24 hours until 90
      hours after PG for heifers that failed to exhibit estrus by 66 hours. For heifers
      in treatment 1 that were inseminated at 90 hours, GnRH (100 MUg) was administered
      concurrent with AI at 90 hours. Heifers in treatment 2 that were inseminated at
      90 hours did not receive GnRH. Estrous response did not differ between treatments
      at 66 hours after PG (treatment 1 = 70%; treatment 2 = 71%; P = 0.58) or during
      the 24-hour delay period (treatment 1 = 59%; treatment 2 = 52%; P = 0.21). There
      was no effect of treatment on pregnancy rates resulting from AI for heifers
      inseminated at 66 hours (treatment 1 = 58%; treatment 2 = 62%; P = 0.86) or 90
      hours (treatment 1 = 44%; treatment 2 = 39%; P = 0.47) after PG; and there was no
      difference between treatments when considering total AI pregnancy rate (treatment
      1 = 54%; treatment 2 = 56%; P = 0.60). Ovulation was confirmed via
      ultrasonography for a subset of heifers that failed to exhibit estrus prior to 90
      hours after PG. For heifers that failed to exhibit estrus by 90 hours, success of
      ovulation did not differ between treatments (treatment 1 = 52%; treatment 2 =
      50%; P = 0.64) nor did AI pregnancy rate (treatment 1 = 24%; treatment 2 = 15%; P
      = 0.97). In summary, when split-time AI was used in conjunction with the 14-day
      CIDR-PG protocol in heifers, comparable pregnancy rates were achieved without
      administering GnRH.

PMID- 27707549
TI  - Twelve-Month Outcomes of Ranibizumab vs. Aflibercept for Neovascular Age-Related
      Macular Degeneration: Data from an Observational Study.
AB  - PURPOSE: To directly compare visual acuity (VA) outcomes with ranibizumab vs.
      aflibercept for eyes with neovascular age-related macular degeneration (nAMD)
      treated in routine clinical practice. DESIGN: Database observational study.
      PARTICIPANTS: Treatment-naive eyes with nAMD tracked by the Fight Retinal
      Blindness outcome registry that commenced anti-vascular endothelial growth factor
      therapy with ranibizumab or aflibercept between December 1, 2013, and January 31,
      2015. Eyes were matched at baseline for VA, age, and choroidal neovascular
      membrane (CNV) size. METHODS: Locally weighted scatterplot smoothing curves were
      used to display VA results. Eyes that switched or discontinued treatment were
      included with their last observation carried forward. MAIN OUTCOME MEASURES:
      Change in mean VA (number of letters read on a logarithm of the minimum angle of
      resolution chart); number of injections and visits; proportion of eyes with
      inactive CNV over 12 months. RESULTS: We identified 394 eyes (197 treated with
      ranibizumab and 197 with aflibercept) from 372 patients who received treatment
      from 34 practitioners. Baseline parameters were well matched. The mean (standard
      deviation [SD]) VA of ranibizumab-treated eyes increased from 58.6 (20.3) letters
      at baseline to 62.3 (23.9) (+3.7 [95% confidence interval {CI} 1.4-6.1]) letters
      (P = 0.001), compared with 58.9 (19.2) letters at baseline to 63.1 (21.5) (+4.26
      [95% CI 2.0-6.5]) letters (P < 0.001) for eyes receiving aflibercept. The
      difference in change in crude VA of 0.6 letters between the 2 groups was not
      statistically significant (P = 0.76), nor was the difference in adjusted mean VA
      of the 2 groups (P = 0.26). In completers, the mean (SD) numbers of injections
      (8.1 [2.1] vs. 8.0 [2.3]; P = 0.27) and visits (9.6 [3.0] vs. 9.5 [3.1]; P =
      0.15) did not differ between the 2 groups. The adjusted proportion of eyes in
      which the CNV lesion was graded as inactive during the study was similar between
      the eyes receiving ranibizumab and aflibercept (74% vs. 77%, respectively; P =
      0.63). CONCLUSIONS: Visual acuity outcomes at 12 months did not differ between
      ranibizumab and aflibercept used for nAMD in this large observational study, nor
      was a difference in treatment frequency found.

PMID- 27707548
TI  - Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study.
AB  - PURPOSE: Primary open-angle glaucoma (POAG) is a major cause of blindness and
      visual disability. Several genetic risk factors for POAG and optic nerve features
      have been identified. We measured the relative risk for glaucoma that these
      factors contribute to participants in the Ocular Hypertension Treatment Study
      (OHTS). DESIGN: Comparative series. PARTICIPANTS: One thousand fifty-seven of
      1636 participants (65%) of the OHTS were enrolled in this genetics ancillary
      study. METHODS: Samples of DNA were available from 1057 OHTS participants. Of
      these, 209 developed POAG (cases) and 848 did not develop glaucoma (controls)
      between 1994 and 2009. The frequencies of 13 risk alleles previously associated
      with POAG or with optic disc features in other cohorts were compared between POAG
      cases and controls in the OHTS cohort using analyses of variance. The 2 largest
      subgroups, non-Hispanic whites (n = 752; 70.7%) and blacks (n = 249, 23.7%), also
      were analyzed separately. The probability of glaucoma developing over the course
      of the OHTS was compared between participants stratified for transmembrane and
      coiled-coil domains 1 (TMCO1) risk alleles using Kaplan-Meier and Cox
      proportional hazards analyses. MAIN OUTCOME MEASURES: Association of POAG with
      known genetic factors. RESULTS: No association was detected between the known
      POAG risk alleles when the OHTS cohort was examined as a whole. However, in the
      subgroup of non-Hispanic whites, allele frequencies at the TMCO1 locus were
      statistically different between cases and controls (P = 0.00028). By 13 years,
      non-Hispanic white participants with TMCO1 risk alleles had a 12% higher
      cumulative frequency of glaucoma developing than participants with no TMCO1 risk
      alleles. Moreover, the Cox proportional hazard analysis demonstrated that TMCO1
      alleles increased relative risk comparable with that of some previously analyzed
      clinical measures (i.e., intraocular pressure). CONCLUSIONS: The size of the OHTS
      cohort and its composition of 2 large racial subgroups may limit its power to
      detect some glaucoma risk factors. However, TMCO1 genotype was found to increase
      the risk of glaucoma developing among non-Hispanic whites, the largest racial
      subgroup in the OHTS cohort, at a magnitude similar to clinical predictors of
      disease that long have been associated with glaucoma.

PMID- 27707550
TI  - Twenty-four-Month Outcomes of the Ranibizumab for Edema of the Macula in Diabetes
      - Protocol 3 with High Dose (READ-3) Study.
AB  - PURPOSE: To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes
      with center-involved diabetic macular edema (DME). DESIGN: Randomized,
      controlled, double-masked (to the dose), interventional, multicenter clinical
      trial. PARTICIPANTS: A total of 152 patients (152 eyes) with DME. METHODS:
      Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n = 77) or 2.0 mg (n =
      75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed
      injections until month 24. MAIN OUTCOME MEASURES: The primary efficacy end point
      of the study was mean change in best-corrected visual acuity (BCVA) and central
      foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in
      BCVA and CFT at month 24, and incidence and severity of systemic and ocular
      adverse events through month 24. RESULTS: A total of 152 eyes were randomized in
      the study. At month 24, the mean improvement from baseline BCVA was +11.06
      letters in the 0.5 mg RBZ group (n = 59) and +6.78 letters in the 2.0 mg RBZ
      group (n = 54) (P = 0.02). The mean numbers of RBZ injections through month 24
      were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively (P = 0.08).
      The mean change in CFT was -192.53 MUm in the 0.5 mg RBZ group and -170.64 MUm in
      the 2.0 mg RBZ group (P = 0.41). By month 24, 3 deaths had occurred in the 0.5 mg
      RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths
      occurred secondary to cardiovascular causes, and 1 death occurred as the result
      of severe pneumonia. All 5 patients with a cardiovascular cause of death had a
      history of coronary heart disease. CONCLUSIONS: At month 24, there were
      significant visual and anatomic improvements in both groups, with subjects in the
      0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month
      6 were largely maintained through month 24. No new safety events were identified.
      In this study population, 2.0 mg RBZ does not appear to provide additional
      benefit over 0.5 mg RBZ.

PMID- 27707551
TI  - The awareness to metabolic syndrome among hospital health providers.
AB  - BACKGROUND: Metabolic syndrome (MetS) was shown to be related to a variety of
      diseases. High level of vigilance for the diagnosis of MetS is expected among
      health providers. We evaluated the level of awareness to MetS among physician and
      nurses working in a central hospital. METHODS AND RESULTS: A specially designed
      anonymous questionnaire was used, including both open and multiple choice
      questions set to evaluate the participant's awareness to MetS. The study included
      126 participants, 71% physicians and 29% nurses. Mean age was 36.2+/-3.8 years.
      Among physicians, 68.5% were residents and 45.5% were internists. 98% of the
      participants stated that they were familiar with the term MetS and that they
      treat MetS patients regularly. Most participants knew the correct number of
      criteria included in MetS definition and the number of criteria needed for MetS
      diagnosis (84% and 90%, respectively). However, only 12% were able to
      discriminate correctly all MetS cases from non-MetS ones. Physicians performed
      better than nurses (15.6% and 3.1%, respectively, P=0.003). Neither, field of
      practice nor seniority was found to have a significant influence on the results.
      The frequency of recommendation for MetS risk factor modulation in the discharge
      files was also analyzed. Such recommendations were scarcely given, with
      cardiology department being the exception (80% of discharge files from cardiology
      department compared with less than 20% in other departments). CONCLUSION: Though
      hospital workers showed high level of awareness to the existence of MetS, they
      failed to differentiate correctly MetS cases from non-MetS ones.

PMID- 27707552
TI  - Comparative Effectiveness of 12 Treatment Strategies for Preventing Contrast
      Induced Acute Kidney Injury: A Systematic Review and Bayesian Network Meta
      analysis.
AB  - BACKGROUND: To simultaneously evaluate the relative efficacy of multiple
      pharmacologic strategies for preventing contrast-induced acute kidney injury
      (AKI). STUDY DESIGN: Systematic review containing a Bayesian network meta
      analysis of randomized controlled trials. SETTING & POPULATION: Participants
      undergoing diagnostic and/or interventional procedures with contrast media.
      SELECTION CRITERIA FOR STUDIES: Randomized controlled trials comparing the active
      drug treatments with each other or with hydration alone. INTERVENTION: Any of the
      following drugs in combination with hydration: N-acetylcysteine (NAC),
      theophylline (aminophylline), fenoldopam, iloprost, alprostadil, prostaglandin
      E1, statins, statins plus NAC, bicarbonate sodium, bicarbonate sodium plus NAC,
      ascorbic acid (vitamin C), tocopherol (vitamin E), alpha-lipoic acid, atrial
      natriuretic peptide, B-type natriuretic peptide, and carperitide. OUTCOMES: The
      occurrence of contrast-induced AKI. RESULTS: The trial network included 150
      trials with 31,631 participants and 4,182 contrast-induced AKI events assessing
      12 different interventions. Compared to hydration, ORs (95% credible intervals)
      for contrast-induced AKI were 0.31 (0.14-0.60) for high-dose statin plus NAC,
      0.37 (0.19-0.64) for high-dose statin alone, 0.37 (0.17-0.72) for prostaglandins,
      0.48 (0.26-0.82) for theophylline, 0.62 (0.40-0.88) for bicarbonate sodium plus
      NAC, 0.67 (0.54-0.81) for NAC alone, 0.64 (0.41-0.95) for vitamins and analogues,
      0.70 (0.29-1.37) for natriuretic peptides, 0.69 (0.31-1.37) for fenoldopam, 0.78
      (0.59-1.01) for bicarbonate sodium, and 0.98 (0.41-2.07) for low-dose statin.
      High-dose statin plus NAC or high-dose statin alone were likely to be ranked the
      best or the second best for preventing contrast-induced AKI. The overall results
      were not materially changed in metaregressions or subgroup and sensitivity
      analyses. LIMITATIONS: Patient-level data were unavailable; unable to include
      some treatment agents; low event rates; imbalanced distribution of participants
      among treatment strategies. CONCLUSIONS: High-dose statins plus hydration with or
      without NAC might be the preferred treatment strategy to prevent contrast-induced
      AKI in patients undergoing diagnostic and/or interventional procedures requiring
      contrast media.

PMID- 27707555
TI  - 'Had we but world enough, and time'.

PMID- 27707556
TI  - Adductor canal block and lateral approach of sciatic nerve block at the midthigh
      level.

PMID- 27707554
TI  - The construction and validity analysis of AQHI based on mortality risk: A case
      study in Guangzhou, China.
AB  - The current air quality indices have been criticized for not capturing combined
      health effects of multiple air pollutants. We proposed an Air Quality Health
      Index (AQHI) based on the air pollution-mortality associations for communicating
      health risks of air pollution. Time-series studies were conducted to estimate the
      associations between air pollutants including sulfur dioxide (SO2), nitrogen
      dioxide (NO2), ozone (O3), suspended particulate matter smaller than 2.5 MUm in
      aerodynamic diameter (PM2.5) and mortality in Guangzhou from 2012 to 2015. The
      sum of excess mortality risk was calculated to construct the AQHI, which was then
      adjusted to an arbitrary scale. We then assessed the validity of AQHI. An
      interquartile increase (IQR) of AQHI was associated with 3.61% [95% confidence
      interval (95% CI), 2.85%-4.37%], 3.73% (95%CI, 2.18%-5.27%) and 4.19% (95%CI,
      2.87%-5.52%) increase of mortality, respiratory and cardiovascular hospital
      admissions, respectively. Compared with the currently used Air Quality Index
      (AQI), AQHI had higher effects on mortality and morbidity. Our study suggests
      that AQHI might comprehensively capture the combined effects of air pollution,
      which make it be a more valid communication tool of air pollution-related health
      risk.

PMID- 27707553
TI  - Preeclampsia and ESRD: The Role of Shared Risk Factors.
AB  - BACKGROUND: Several registry-based studies, using diagnostic codes, have
      suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD).
      However, because the 2 diseases share risk factors, the true nature of their
      association remains uncertain. Our goals were to conduct a population-based study
      to determine the magnitude of the association between preeclampsia and ESRD and
      evaluate the role of shared risk factors. STUDY DESIGN: Population-based nested
      case-control study. SETTING & PARTICIPANTS: The US Renal Data System was used to
      identify women with ESRD from a cohort of 34,581 women who gave birth in 1976 to
      2010 in Olmsted County, MN. 44 cases of ESRD were identified and each one was
      matched to 2 controls based on year of birth (+/-1 year), age at first pregnancy
      (+/-2 years), and parity (+/-1 or >=4). PREDICTOR: Preeclamptic pregnancy,
      confirmed by medical record review. OUTCOME: ESRD. MEASUREMENTS: Prepregnancy
      serum creatinine and urine protein measurements were recorded. Comorbid
      conditions existing prior to pregnancy were abstracted from medical records and
      included kidney disease, obesity, diabetes, and hypertension. RESULTS: There was
      evidence of kidney disease prior to the first pregnancy in 9 of 44 (21%) cases
      and 1 of 88 (<1%) controls. Per chart review, 8 of 44 (18%) cases versus 4 of 88
      (5%) controls had preeclamptic pregnancies (unadjusted OR, 4.0; 95% CI, 1.21
      13.28). Results were similar after independent adjustment for race, education,
      diabetes, and hypertension prior to pregnancy. However, the association was
      attenuated and no longer significant after adjustment for obesity (OR, 3.25; 95%
      CI, 0.93-11.37). LIMITATIONS: The limited number of ESRD cases and missing data
      for prepregnancy kidney function. CONCLUSIONS: Our findings confirm that there is
      a sizable association between preeclampsia and ESRD; however, obesity is a
      previously unexplored confounder. Pre-existing kidney disease was common, but not
      consistently coded or diagnosed.

PMID- 27707557
TI  - Where the thread of home births never broke - An interview with Susanne Houd.
AB  - BACKGROUND: The option of a planned home birth defies medical and social
      normativity across countries. In Denmark, despite the dramatic decline in the
      home birth rates between 1960 and 1980, the right to choose the place of birth
      was preserved. Little has been produced documenting this process. AIM: To present
      and discuss Susanne Houd's reflection on the history and social dynamics of home
      birth in Denmark, based in an in-depth interview. METHODS: This paper is part of
      wider Short Term Scientific Mission (STSM), in which this interview was framed as
      oral history. The whole interview transcript is presented, keeping the highest
      level of detail. FINDINGS: In Susanne Houd's testimony, four factors were
      highlighted as contributing to the decline in the rate of home births from the
      1960s to the 1970s: new maternity hospitals; the development of obstetrics as a
      research-based discipline; the compliance of midwives; and a shift in women's
      preference, favouring hospital birth. The development of the Danish home birth
      models was described by Susanne Houd in regard to the processes associated with
      the medicalisation of childbirth, the role of consumers, and the changing
      professional dynamics of midwifery. CONCLUSION: An untold history of home birth
      in Denmark was documented in this testimony. The Danish childbirth
      hospitalisation process was presented as the result of a complex interaction of
      factors. Susanne Houd's reflections reveal how the concerted action of consumers
      and midwives, framed as a system-challenging praxis, was the cornerstone for the
      sustainability of home birth models in Denmark.

PMID- 27707558
TI  - A comparison of language use in pro- and anti-vaccination comments in response to
      a high profile Facebook post.
AB  - BACKGROUND: Vaccinations are important for controlling the spread of disease, yet
      an increasing number of people are distrustful of vaccines, and choose not to
      (fully) vaccinate themselves and their children. One proposed contributor to this
      distrust is anti-vaccination misinformation available on the internet, where
      people search for and discuss health information. The language people use in
      these discussions can provide insights into views about vaccination. METHODS:
      Following a prominent Facebook post about childhood vaccination, language used by
      participants in a comment thread was analysed using LIWC (Linguistic Inquiry and
      Word Count). Percentage of words used across a number of categories was compared
      between pro-vaccination, anti-vaccination, and unrelated (control) comments.
      RESULTS: Both pro- and anti-vaccination comments used more risk-related and
      causation words, as well as fewer positive emotion words compared to control
      comments. Anti-vaccine comments were typified by greater analytical thinking,
      lower authenticity, more body and health references, and a higher percentage of
      work-related word use in comparison to pro-vaccine comments, plus more money
      references than control comments. In contrast, pro-vaccination comments were more
      authentic, somewhat more tentative, and evidenced higher anxiety words, as well
      as more references to family and social processes when compared to anti
      vaccination comments. CONCLUSION: Although the anti-vaccination stance is not
      scientifically-based, comments showed evidence of greater analytical thinking,
      and more references to health and the body. In contrast, pro-vaccination comments
      demonstrated greater comparative anxiety, with a particular focus on family and
      social processes. These results may be indicative of the relative salience of
      these issues and emotions in differing understandings of the benefits and risks
      of vaccination. Text-based analysis is a potentially useful and ecologically
      valid tool for assessing perceptions of health issues, and may provide unique
      information about particular concerns or arguments expressed on social media that
      could inform future interventions.

PMID- 27707559
TI  - Treatment of Chlamydia-associated ocular disease via a recombinant protein based
      vaccine in the koala (Phascolarctos cinereus).
AB  - Koalas (Phascolarctos cinereus) are affected by debilitating chlamydial disease
      that can lead to blindness, infertility, and death. The causative agent is the
      intracellular bacterium Chlamydia pecorum. While antibiotics can be used to treat
      koala chlamydial infection, they are often ineffective or cause severe dysbiosis
      to the animal's unique gut flora. Recent work has progressed on the development
      of a protective vaccine for Chlamydia in the koala. This study demonstrates that
      the use of a vaccine can have a positive effect in koalas already with clinical
      signs of ocular disease, suggesting a possible therapeutic effect and an
      alternative to antibiotic therapy.

PMID- 27707560
TI  - Application of a real time Polymerase Chain Reaction (PCR) assay for the early
      diagnosis of human leptospirosis in Sri Lanka.
AB  - Leptospirosis has a major impact on health in Sri Lanka but is probably grossly
      under-recognized due to difficulties in clinical diagnosis and lack of diagnostic
      laboratory services. The objective of this study was to establish and evaluate a
      SYBR Green-based real-time Polymerase Chain Reaction (rt-PCR) assay for early,
      rapid and definitive laboratory diagnosis of leptospirosis in Sri Lanka. The rt
      PCR assay was established and analytical specificity and sensitivity were
      determined using reference DNA samples. Evaluation of the assay for diagnosis of
      clinical samples was performed using two panels of serum samples obtained from
      111 clinically suspected adult patients. Patients were confirmed as leptospirosis
      (n = 65) and non-leptospirosis (n = 30) by the Patoc - MAT. Other 16 samples gave
      ambiguous results. The analytical sensitivity of the rt-PCR was approximately 60
      genome copies and no cross-reactivity was observed with saprophytic Leptospira
      spp. and other pathogenic microorganisms. Based on confirmation with Patoc-MAT on
      paired samples this corresponds to a diagnostic sensitivity and specificity of
      67.7% (44/65) and 90.0% (27/30), respectively. This study showed that rt-PCR has
      the potential to facilitate rapid and definitive diagnosis of leptospirosis
      during early phase of infection in Sri Lanka.

PMID- 27707561
TI  - Awareness of Genetic Coronary Risk Score Improves Blood Pressure Control in
      Hypertensive Patients.

PMID- 27707562
TI  - Spanish Heart Transplantation Registry. 27th Official Report of the Spanish
      Society of Cardiology Working Group on Heart Failure and Heart Transplantation
      (1984-2015).
AB  - INTRODUCTION AND OBJECTIVES: The present article reports the characteristics and
      results of heart transplants in Spain since this therapeutic modality was first
      used in May 1984. METHODS: We describe the main features of recipients, donors,
      surgical procedures, and results of all heart transplants performed in Spain
      until December 31, 2015. RESULTS: A total of 299 cardiac transplants were
      performed in 2015, with the whole series comprising 7588 procedures. The main
      transplant features in 2015 were similar to those observed in recent years. A
      remarkably high percentage of transplants were performed under emergency
      conditions and there was widespread use of circulatory assist devices,
      particularly continuous-flow left ventricular assist devices prior to transplant
      (16% of all transplants). Survival has significantly improved in the last decade
      compared with previous time periods. CONCLUSIONS: During the last few years,
      between 250 and 300 heart transplants have consistently been performed each year
      in Spain. Despite a more complex clinical context, survival has increased in
      recent years.

PMID- 27707563
TI  - "Subclinical" Leaflet Thrombosis in Transcatheter Aortic Valve Implantation: A
      Latent Risk?

PMID- 27707564
TI  - A Systematic Review and Meta-Analysis Examining the Differences Between
      Nonsurgical Management and Percutaneous Fixation of Minimally and Nondisplaced
      Scaphoid Fractures.
AB  - PURPOSE: The optimal management of undisplaced scaphoid fractures remains
      controversial. A systematic review was conducted to assess the outcomes of acute,
      undisplaced scaphoid fractures managed with cast immobilization versus
      percutaneous or miniopen screw fixation in terms of time to return to work (RTW),
      time to union, and morbidity. METHODS: PubMed MEDLINE, Ovid MEDLINE, EMBASE,
      SCOPUS, and Cochrane electronic databases were searched over the period 1974 to
      2015. Key words included "scaphoid fracture," "navicular fracture," "hand,"
      "immobilization," "cast," "conservative," "percutaneous," "screw fixation," "mini
      open," and "minimally invasive." A 2-step review process was done by 2
      independent reviewers (H.A. and J.K.) using the following criteria: (1) acute
      undisplaced scaphoid fracture, (2) English language, (3) RTW duration objectively
      reported, (5) age older than 15 years, and (5) studies with more than 10
      patients. Patient demographics, duration of immobilization, time to RTW, time to
      union, and complications were extracted. The methodological quality of each study
      included was assessed independently. Meta-analysis was performed for comparative
      trials. RESULTS: Ten studies met the inclusion criteria: 6 comparative studies
      and 4 case series. Patients were divided into 2 groups: cast immobilization
      (group 1) and percutaneous fixation (group 2). Average time to RTW was 77 days
      for group 1 versus 46 days for group 2. Average time to radiographic union was 79
      days for group 1 versus 44 days for group 2. There was no significant difference
      in complication rate between the groups (7% in group 1 vs 14% in group 2).
      CONCLUSIONS: Percutaneous fixation of acute undisplaced scaphoid fractures has
      union rates comparable with those of nonsurgical cast immobilization but with
      faster RTW and time to union without a significant difference in complication
      rate. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

PMID- 27707565
TI  - Relationship Between Ulnar Variance, Cortical Bone Density, and Load to Failure
      in the Distal Radius at the Typical Site of Fracture Initiation.
AB  - PURPOSE: Increased ulnar variance has been shown to lead to diminished load borne
      by the distal radius. The purpose of this study was to determine the correlations
      among ulnar variance, bone mineral density, and load to failure at the distal
      radius. METHODS: Posteroanterior radiographs and computed tomographic scans were
      taken of 12 cadaveric forearms in neutral rotation. Ulnar variance was measured
      for each wrist by the method of perpendiculars. Measurements of cortical,
      trabecular, and combined bone density were made at the distal radius. We
      performed linear regression analysis and correlation analysis to determine the
      relationship between bone densities and ulnar variance measurements. Next, we
      loaded the 12 cadaveric radii to failure under axial compression. Linear
      regression analysis and correlation analysis were then performed to determine the
      relationship between load to failure and both ulnar variance and cortical
      density. RESULTS: Increased ulnar variance was significantly correlated with
      decreased cortical bone density at the distal radius and both were correlated
      with decreased load to failure. We found no correlation between ulnar variance
      and trabecular density or combined trabecular and cortical bone density at the
      distal radius. CONCLUSIONS: Our study found that increased ulnar variance and
      decreased cortical bone mineral density correlates with decreased load to failure
      under axial compression. CLINICAL RELEVANCE: Ulnar variance is linked to both
      bone quality and load to failure at the distal radius.

PMID- 27707566
TI  - Simultaneous control of glycemic, blood pressure, and lipid significantly reduce
      the risk of renal progression in diabetes patients.
AB  - BACKGROUND AND AIM: Hyperglycemic, hypertension, and lipid abnormalities are risk
      factors for diabetic kidney disease However, no study has discussed the
      association of the simultaneous control of glycemic, blood pressure, and lipids
      with renal function among diabetes patients. Thus, this study examined the
      interactive effects of the intensive control of all 3 conditions on the
      progression of renal function. MATERIALS AND METHODS: The study population was
      derived from eight hospitals in Taiwan from October 2008 to April 2015.
      Demographic characteristics were collected using structured questionnaires.
      Clinical variables were obtained from medical chart review. The renal progression
      was defined as a decline in the eGFR by more than 25% according to the baseline
      eGFR. RESULTS: Total of 1602 diabetes patients were included in the study
      analysis, the mean age was 63.03+/-10.98years, 55.56% were men. Compared to the
      simultaneous control of glycemic, blood pressure and lipid group, the poor
      control of all three diseases had the highest risk of renal progression, with an
      adjusted OR of 2.21 (95% CI, 1.26-3.86). Even if the patients with an intensive
      control of lipid, the result showed that the poor control of both glycemic and
      hypertension was associated with the increased risk of renal progression than the
      reference group. CONCLUSION: This study demonstrated that the simultaneous poor
      control of glycemic, blood pressure, and lipid had the highest risk of renal
      progression. Thus, patients with type 2 diabetes should not only control glycemic
      but also manage their blood pressure and lipid.

PMID- 27707567
TI  - The variability of statewide prehospital drug-facilitated intubation protocols in
      the United States.

PMID- 27707568
TI  - Ultrasound for retrograde intubation: old wine in a new bottle.

PMID- 27707570
TI  - Stream invertebrate community structure at Canadian oil sands development is
      linked to concentration of bitumen-derived contaminants.
AB  - In Canada, the Athabasca oil sands deposits are a source of bitumen-derived
      contaminants, reaching the aquatic environment via various natural and
      anthropogenic pathways. The ecological effects of these contaminants are under
      debate. To quantify the effects of bitumen-derived contaminants we monitored the
      aquatic exposure of polycyclic aromatic hydrocarbons (PAHs), metals, and
      naphthenic acids as well as the invertebrate community in the Athabasca River and
      its tributaries. PAH concentrations over 3 consecutive years were related to
      discharge and were highest in the year with high autumn rainfall. In the year
      with the highest PAH concentrations, these were linked with adverse effects on
      the aquatic invertebrate communities. We observed relative effects of the
      composition and concentration of contaminants on the invertebrate fauna. This is
      reflected by the composition and abundance of invertebrate species via the use of
      the species' traits "physiological sensitivity" and "generation time". Applying
      the SPEAR approach we observed alterations of community structure in terms of an
      increased physiological sensitivity and a decrease of generation time for the
      average species. These effects were apparent at concentrations 100 times below
      the acute sensitivity of the standard test organism Daphnia magna. To rapidly
      identify oil sands related effects in the field we designed a biological
      indicator system, SPEARoil, applicable for future routine monitoring.

PMID- 27707569
TI  - Dual cocaine and methamphetamine cardiovascular toxicity: rapid resolution with
      labetalol.

PMID- 27707571
TI  - Train-induced field vibration measurements of ground and over-track buildings.
AB  - Transit-oriented development, such as metro depot and over-track building
      complexes, has expanded rapidly over the last 5years in China. Over-track
      building construction has the advantage of comprehensive utilization of land
      resources, ease of commuting to work, and provide funds for subway construction.
      But the high frequency of subway operations into and out of the depots can
      generate excessive vibrations that transmit into the over track buildings,
      radiate noise within the buildings, hamper the operation of vibration sensitive
      equipment, and adversely affect the living quality of the building occupants.
      Field measurements of vibration during subway operations were conducted at
      Shenzhen, China, a city of 10.62 million people in southern China. Considering
      the metro depot train testing line and throat area train lines were the main
      vibration sources, vibration data were captured in five measurement setups. The
      train-induced vibrations were obtained and compared with limitation of FTA
      criteria. The structure-radiated noise was calculated using measured vibration
      levels. The vertical vibration energy directly passed through the columns on both
      sides of track into the platform, amplifying vibration on the platform by up to
      6dB greater than ground levels at testing line area. Vibration amplification
      around the natural frequency in the vertical direction of over-track building
      made the peak values of indoor floor vibration about 16dB greater than outdoor
      platform vibration. We recommend to carefully examining design of new over-track
      buildings within 40m on the platform over the throat area to avoid excessive
      vertical vibrations and noise. For both buildings, the measured vertical
      vibrations were less than the FTA limit. However, it is demonstrated that the
      traffic-induced high-frequency noise has the potential to annoy occupants on the
      upper floors.

PMID- 27707572
TI  - Accumulation of mineral oil saturated hydrocarbons (MOSH) in female Fischer 344
      rats: Comparison with human data and consequences for risk assessment.
AB  - Female Fischer 344 rats were orally exposed to a mixture of mineral oil saturated
      hydrocarbons (MOSH) of broad molecular mass range at doses of 40, 400 and
      4000mg/kg feed. Amounts and compositions of the MOSH were analyzed in liver,
      spleen, adipose tissue and the carcass after exposure during 30, 60, 90 and 120d
      as well as after 90d exposure followed by 30d depuration. At 40mg/kg in the feed,
      after 30d of exposure, 10.9% of the ingested MOSH were recovered from the animal
      body; after 90d plus 30d depuration it was 3.9%. In liver and spleen, the maximum
      retention in terms of molecular mass (simulated distillation) was at n-C29; in
      adipose tissue and carcass it was at n-C15/16. The differentiation between MOSH
      below and above n-C25 (Class I versus Class II and III oils), used for present
      regulation, is not supported by the present data on accumulation; structural
      characteristics seem more pertinent than molecular mass. Concentrations in the
      tissues increased far less than proportionally with the dose, rendering linear
      extrapolation to low doses questionable. No steady state was reached after 120d.
      In fact, comparing with the concentrations in human tissues at the estimated
      exposure, extrapolation from animal experiments seems to grossly underestimate
      human internal exposure. Comprehensive two-dimensional gas chromatography (GCxGC)
      was used to characterize the MOSH residues in the tissues with the aim of
      identifying the most strongly accumulated types. In the liver and spleen, the
      highly branched hydrocarbons dominated, whereas in the adipose tissue it was the
      n-alkanes and species with main n-alkyl moieties. Strong MOSH accumulation is not
      of concern per se, but the safety at the high concentrations in human tissues
      needs to be re-evaluated, possibly taking into account also end points other than
      granuloma formation.

PMID- 27707573
TI  - Reducing production of taste and odor by deep-living cyanobacteria in drinking
      water reservoirs by regulation of water level.
AB  - Abatement and control of algae, producing toxins and creating taste & odor (T&O)
      in drinking water sources, is a major challenge for water supply. In this study
      we proposed a strategy based on water level regulation for the control of odor
      producing cyanobacteria in source water. Miyun Reservoir, the main surface water
      source for Beijing, has been suffering from 2-methylisoborneol (2-MIB) induced
      T&O problems caused by deep-living Planktothrix sp. since 2002. The biomass of
      deep-living Planktothrix in Miyun Reservoir was found to be mainly governed by
      the water depth above its sediment habitat. An algorithm for water level
      regulation aiming to minimize the risk for T&O in different types of reservoirs
      is proposed. The study demonstrates that risk for T&O can be minimized by
      increasing the water level in Miyun Reservoir. The high-risk area can be reduced
      by about 2.91% (0.61% to 5.76%) of surface area for each meter increase in the
      water level, when the water level is lower than 145m. More specifically, the
      water level needs to be raised to higher than 147.7ma.s.l. from 131.0m in order
      to obtain an acceptable risk level (ARL) of 10%. This management strategy to
      abate T&O problems is simpler and cheaper to implement compared to traditional
      physical, chemical and biological techniques. Moreover, it has no apparent
      negative impact on water quality and aquatic organisms.

PMID- 27707574
TI  - Edge effects on N2O, NO and CH4 fluxes in two temperate forests.
AB  - Forest ecosystems may act as sinks or sources of nitrogen (N) and carbon (C)
      compounds, such as the climate relevant trace gases nitrous oxide (N2O), nitric
      oxide (NO) and methane (CH4). Forest edges, which catch more atmospheric
      deposition, have become important features in European landscapes and elsewhere.
      Here, we implemented a fully automated measuring system, comprising static and
      dynamic measuring chambers determining N2O, NO and CH4 fluxes along an edge-to
      interior transect in an oak (Q. robur) and a pine (P. nigra) forest in northern
      Belgium. Each forest was monitored during a 2-week measurement campaign with
      continuous measurements every 2h. NO emissions were 9-fold higher than N2O
      emissions. The fluxes of NO and CH4 differed between forest edge and interior,
      but not for N2O. This edge effect was more pronounced in the oak than in the pine
      forest. In the oak forest, edges emitted less NO (on average 60%) and took up
      more CH4 (on average 177%). This suggests that landscape structure can play a
      role in the atmospheric budgets of these climate relevant trace gases. Soil
      moisture variation between forest edge and interior was a key variable explaining
      the magnitude of NO and CH4 fluxes in our measurement campaign. To better
      understand the environmental impact of N and C trace gas fluxes from forest
      edges, additional and long-term measurements in other forest edges are required.

PMID- 27707575
TI  - First observations of saturopeaking: Characteristics and implications.
AB  - During the monitoring of total dissolved gas (TDG) saturation in the
      Vetlefjordelva River in western Norway in 2014-2015, characteristic waves of
      supersaturated water were discovered. These waves were significantly correlated
      with hydropower operation, which was run by hydropeaking (R2=0.82, p<0.001). The
      TDG saturation varied between 99% and 108%, with a median of 105%. The term
      "saturopeaking" is introduced for these waves, defined as the artificial, rapid,
      periodic and frequent fluctuation of gas saturation caused by hydropeaking.
      Hydropeaking is recognized as hydropower operation that rapidly fluctuates
      according to the electricity market demand. Though the observed TDG saturation
      levels were moderate and not likely to cause acute effects on biota, we expect
      that the observed saturopeaking may have significant ecological impacts in
      general, especially in cases with TDG saturation levels >110^% which is
      considered as potentially lethal for fish in rivers.

PMID- 27707576
TI  - Vulnerability of groundwater resources to nitrate pollution: A simple and
      effective procedure for delimiting Nitrate Vulnerable Zones.
AB  - This research was undertaken to further our understanding of the factors involved
      in nonpoint-source nitrate pollution of groundwater. The shortcomings of some of
      the most commonly used methods for assessing groundwater vulnerability have been
      analysed and a new procedure that incorporates key improvements has been
      proposed. The new approach (LU-IV procedure) allows us to assess and map
      groundwater vulnerability to nitrate pollution and to accurately delimit the
      Nitrate Vulnerable Zones. The LU-IV procedure proved more accurate than the most
      widely used methods to assess groundwater vulnerability (DRASTIC, GOD), when
      compared with nitrate distribution in the groundwater of 46 aquifers included in
      the study (using the drainage basin as the unit of analysis). The proposed
      procedure stands out by meeting the following requirements: (1) it uses readily
      available parameters that provide enough data to feed the model, (2) it excludes
      redundant parameters, (3) it avoids the need to assign insufficiently contrasted
      weights to parameters, (4) it assess the whole catchment area that potentially
      drains N-polluted waters into the receptor aquifer, (5) it can be implemented
      within a GIS, and (6) it provides a multi-scale representation. As the LU-IV
      procedure has been demonstrated to be a reliable tool for delimiting NVZ, it
      could be particularly interesting to use it in countries where certain types of
      environmental data are either not available or have only limited availability.
      Based on this study (and according to the LU-IV procedure), it was concluded that
      an area of at least 1728km2 should be considered as NVZ. This sharply contrasts
      with the current 328km2 officially designated in the study area by the Spain's
      regional administrations. These results highlight the need to redefine the
      current NVZ designation, which is essential for an appropriate implementation of
      action programmes designed to restore water quality in line with Directive
      91/676/EEC.

PMID- 27707577
TI  - Enterococcus gallinarum and Chilaiditi syndrome in peritoneal dialysis.

PMID- 27707578
TI  - Incremental hemodialysis schedule at the start of renal replacement therapy.

PMID- 27707579
TI  - Multiple gastrointestinal metastases of Merkel cell carcinoma.
AB  - Merkel cell carcinoma is an aggressive skin malignancy. Primary Merkel cell
      carcinomas are treated by wide radical excision with or without adjuvant
      radiotherapy, while benefits of adjuvant chemotherapy remain doubtful. There are
      only several cases of gastrointestinal metastases of Merkel cell carcinoma
      reported so far. We report a case of recurrent Merkel cell carcinoma with
      metastases to the stomach and the small intestines after wide excision of primary
      Merkel cell carcinoma.

PMID- 27707580
TI  - Gastric greater curvature plication combined with Nissen fundoplication in the
      treatment of gastroesophageal reflux disease and obesity.
AB  - BACKGROUND AND AIM: Established anti-reflux procedures such as fundoplications
      are less efficient in obese patients. The aim of this study was to investigate
      clinical effectiveness of the fundoplication combined with gastric greater
      curvature plication in the treatment of gastroesophageal reflux disease (GERD) in
      obese patients. MATERIALS AND METHODS: During the period from June 2010 to
      September 2014, patients operated for GERD with BMI from 30 to 39.9kg/m2 were
      included into the prospective study. Laparoscopic Nissen fundoplication (LNF,
      n=58) was performed until February 2013 and later laparoscopic Nissen
      fundoplication was combined with gastric greater curvature plication (LNFGP,
      n=56). The groups were compared according to the control of GERD and weight loss.
      RESULTS: In LNF group there were significantly more males, patients had lower BMI
      and longer duration of GERD symptoms. Duration of surgery was significantly
      longer in LNFGP group, 96.5 (17.3)min vs. 59.8 (16.1)min (P<0.0001).
      Postoperative morbidity was similar, 3.6% and 3.4% in LNFGP and LNF groups,
      respectively (P=0.9539). The average percentage of excess BMI loss after 12
      months was 45.3 (5.8) in LNFGP group as compared to 18.4 (4.6) in LNF group
      (P<0.0001). Significantly more patients experienced remission or improvement of
      type 2 diabetes mellitus (P=0.03) and hypercholesterolemia (P=0.0001) in LNFGP
      group. No significant differences between the groups in postoperative DeMeester
      score, GERD-HRQL mean score, overall satisfaction and healing of esophagitis were
      observed. CONCLUSIONS: LNFGP took significantly longer time to perform, but
      resulted in significantly higher weight reduction and remission/improvement of
      comorbidities. Both procedures produced similar anti-reflux effect.

PMID- 27707581
TI  - Comparative Outcome Analysis of Arthroscopic-Assisted Versus Open Reduction and
      Fixation of Trans-scaphoid Perilunate Fracture Dislocations.
AB  - PURPOSE: To compare union rates and clinical and radiological outcomes of
      arthroscopic-assisted reduction and fixation with those of open reduction and
      fixation in patients with trans-scaphoid perilunate fracture dislocations.
      METHODS: This retrospective study included consecutive patients with trans
      scaphoid PLFDs who underwent arthroscopic-assisted reduction and fixation (group
      A) or open reduction and fixation (group O), and who were followed up for a
      minimum of 2 years between May 2005 and March 2013. We excluded initially missed
      patients. Each different surgeon who was on call had performed each experienced
      operation. These clinical outcomes were assessed: range of motion, grip strength,
      Mayo wrist score, and Disabilities of Arm, Shoulder, and Hand (DASH) score. For
      radiologic outcomes, the scapholunate angle, radiolunate angle, and
      lunotriquetral distance were measured. RESULTS: The total number of included
      patient was 20 (11 in group A and 9 in group O). Scaphoid union occurred in all
      patients except 1 individual (11 of 11 in group A, and 8 of 9 in group O). At the
      last follow-up, the mean flexion-extension arc was significantly greater in group
      A (125.0 degrees ) than in group O (105.6 degrees ) (P = .028). The mean grip
      strength was 81.1% that of the contralateral side in group A and 80.9% in group O
      (P = .594). The mean Mayo wrist score was 85.5 in group A and 79.4 in group O (P
      = .026), and the mean DASH score was 10.6 in group A and 20.8 in group O (P =
      .001); however, only the DASH score showed a minimum clinically important
      difference. The mean scapholunate angle, radiolunate angle, and lunotriquetral
      distance were similar between the 2 groups: 47.2 degrees , 1.7 degrees , and 2.0
      mm in group A and 48.8 degrees , 5.6 degrees , and 2.1 mm in group O,
      respectively. CONCLUSIONS: Although both arthroscopic and open techniques
      achieved stability of the injured wrists in patients with trans-scaphoid PLFDs,
      it is shown that the arthroscopic-assisted technique showed a clinically
      meaningful better DASH score and greater flexion-extension arc with other
      parameters being similar. LEVEL OF EVIDENCE: Level III, retrospective comparative
      study.

PMID- 27707582
TI  - Time-Dependent Effects of Arthroscopic Conditions on Human Articular Cartilage:
      An In Vivo Study.
AB  - PURPOSE: To assess time-dependent effects of arthroscopic conditions on human
      articular cartilage in vivo. METHODS: From each of 10 patients undergoing
      multiligament reconstruction of the knee under our routine arthroscopic
      conditions (gravity irrigation of 0.9% normal saline solution at room temperature
      with 150 cm H2O [110 mm Hg] pressure and pneumatic tourniquet under 270 mm Hg
      pressure), cartilage specimens were harvested from the lateral edge of the
      femoral notch at the beginning of the operation (baseline) and at 15-, 30-, 45-,
      and 60-minute time points during the operation. H&E staining and safranin O
      staining were used to evaluate the tissue structure, chondrocytes, and
      extracellular matrix (ECM) of the articular cartilage. Chondrocyte viability was
      evaluated, and a biochemical examination of the ECM was performed to detect
      changes in glycosaminoglycan and collagen content. The expression levels of genes
      associated with proinflammatory cytokines, ECM metabolism, and chondrocyte
      apoptosis of the articular cartilage were evaluated. RESULTS: At the 45- and 60
      minute time points, an obvious impairment of tissue structure, a significant
      decrease in glycosaminoglycan content, and a significantly lower percentage
      chondrocyte viability were observed, as compared with baseline (P < .05).
      Regarding the tissue collagen content, no significant change was detected at any
      time point (P > .05). The gene expression examination at the 45- and 60-minute
      time points detected significant upregulation of interleukin 1beta and tumor
      necrosis factor alpha (P < .05), indicating an inflammatory response by the
      chondrocytes, and significant upregulation of aggrecanase 1 (P < .05), which
      indicates catabolism or the disturbance of aggrecan metabolism. CONCLUSIONS:
      Under current arthroscopic conditions, an operative duration of 45 minutes or
      longer can cause detrimental structural, biochemical, and metabolic effects on
      human articular cartilage. CLINICAL RELEVANCE: Arthroscopic skills should always
      be improved to reduce operation time and thus minimize the potential detrimental
      effects of arthroscopic conditions on articular cartilage.

PMID- 27707583
TI  - Intranasal administration of IL-35 inhibits allergic responses and symptoms in
      mice with allergic rhinitis.
AB  - BACKGROUND: IL-35 was recently identified as an anti-inflammatory cytokine. We
      previously reported that recombinant fusion protein of murine IL-35 and human
      IgG1 Fc fragment (rIL-35) reduced Th2 cytokines (IL-4 and IL-5) in vitro.
      However, it is unclear whether IL-35 can attenuate nasal allergic responses and
      symptoms of allergic rhinitis in vivo. METHODS: To investigate the in vivo effect
      of IL-35 on allergic rhinitis in mice, mice were sensitized with ovalbumin (OVA).
      Intranasal administration of rIL-35 and intranasal challenge of OVA were then
      performed. Nasal symptoms were estimated after the last nasal challenge. Nasal
      tissue and cervical lymph nodes (CLN) were collected. OVA-specific IgE in sera,
      OVA-specific T cell response, and the production of cytokines (IL-4, IL-5, and IL
      10) stimulated by the OVA antigen were measured. The transcription level of Foxp3
      and the frequency of CD4+CD25+ regulatory T cells were also measured. RESULTS:
      rIL-35 significantly inhibited the number of sneezes and nasal rubbing movements.
      It also reduced the number of eosinophils in the nasal mucosa and significantly
      decreased the level of OVA-specific IgE, the OVA-specific T cell proliferation,
      and the production of IL-4 and IL-5. Furthermore, rIL-35 significantly increased
      the production of IL-10, the transcription level of Foxp3, and the frequency of
      CD4+CD25+ regulatory T cells. CONCLUSIONS: This study showed for the first time
      that rIL-35 inhibits nasal allergic responses and symptoms in mice, and that rIL
      35 increases IL-10, Foxp3, and CD4+CD25+ regulatory T cells in CLN. This study
      also suggests that intranasal administration of IL-35 can attenuate allergic
      rhinitis.

PMID- 27707584
TI  - Epithelial-mesenchymal transition in pediatric nephropathies.
AB  - INTRODUCTION: Epithelial-mesenchymal transition (EMT) is a process in which
      epithelial cells may express mesenchymal cell markers with subsequent change in
      their functions, and it may be part of the etiopathogenesis of kidney disease.
      OBJECTIVE: The aim of this study was to evaluate the immunexpression of some EMT
      inducers and markers in frequent nephropathies in pediatric patients. METHODS: 59
      patients aged 2-18 years old were selected and divided into 6 groups of frequent
      nephropathies in children and adolescents, as well as one control group. Urea and
      creatinine data of the patients were recorded. TGF-beta3, fibronectin, alpha-SMA
      and vimentin were evaluated by immunohistochemistry. RESULTS: Glomerular TGF
      beta3 was higher in the Lupus Nephritis and Acute Diffuse Glomerulonephritis
      (ADGN) groups than in the control group. Glomerular fibronectin was higher in the
      Podocytopathy, Lupus Nephritis, ADGN and Membranous Glomerulopathy patients than
      in control subjects. The expression of alpha-SMA was higher in the
      tubulointerstitial compartment of ADGN and Membranous Glomerulopathy groups than
      in the control group. Glomerular alpha-SMA was higher in ADGN patients than in
      control and Berger's Disease groups. Glomerular vimentin was higher in
      individuals with ADGN than in those with Podocytopathy, Lupus Nephritis, Berger's
      Disease and Thin Basement Membrane Disease/Alport Syndrome. There was a positive
      correlation between fibronectin in the tubulointerstitial compartment and
      creatinine levels, between alpha-SMA and vimentin in both tubulointerstitial and
      glomerular compartments, and between urea and creatinine levels of patients,
      regardless of their nephropathy (p<0.05 for all results). CONCLUSION: These
      markers may possibly be used as indicators of renal functional impairment in
      various nephropathies in pediatric patients.

PMID- 27707586
TI  - Physiology for the pulmonary functional imager.
AB  - As pulmonary functional imaging moves beyond the realm of the radiologist and
      physicist, it is important that imagers have a common language and understanding
      of the relevant physiology of the lung. This review will focus on key
      physiological concepts and pitfalls relevant to functional lung imaging.

PMID- 27707588
TI  - Brain Networks and alpha-Oscillations: Structural and Functional Foundations of
      Cognitive Control.
AB  - The most salient electrical signal measured from the human brain is the alpha
      rhythm, neural activity oscillating at ~100ms intervals. Recent findings
      challenge the longstanding dogma of alpha-band oscillations as the signature of a
      passively idling brain state but diverge in terms of interpretation. Despite firm
      correlations with behavior, the mechanistic role of the alpha-rhythm in brain
      function remains debated. We suggest that three large-scale brain networks
      involved in different facets of top-down cognitive control differentially
      modulate alpha-oscillations, ranging from power within and synchrony between
      brain regions. Thereby, these networks selectively influence local signal
      processing, widespread information exchange, and ultimately perception and
      behavior.

PMID- 27707585
TI  - The role of hyperpolarized 129xenon in MR imaging of pulmonary function.
AB  - In the last two decades, functional imaging of the lungs using hyperpolarized
      noble gases has entered the clinical stage. Both helium (3He) and xenon (129Xe)
      gas have been thoroughly investigated for their ability to assess both the global
      and regional patterns of lung ventilation. With advances in polarizer technology
      and the current transition towards the widely available 129Xe gas, this method is
      ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas
      lung MRI is limited to selected academic institutions; yet, the promising results
      from initial clinical trials have drawn the attention of the pulmonary medicine
      community. HP 129Xe MRI provides not only 3-dimensional ventilation imaging, but
      also unique capabilities for probing regional lung physiology. In this review
      article, we aim to (1) provide a brief overview of current ventilation MR imaging
      techniques, (2) emphasize the role of HP 129Xe MRI within the array of different
      imaging strategies, (3) discuss the unique imaging possibilities with HP 129Xe
      MRI, and (4) propose clinical applications.

PMID- 27707587
TI  - Bacterial extract (OM-85) with human-equivalent doses does not inhibit the
      development of asthma in a murine model.
AB  - BACKGROUND: OM-85 is an immunostimulant bacterial lysate, which has been proven
      effective in reducing the number of lower airways infections. We investigated the
      efficacy of the bacterial lysate OM-85 in the primary prevention of a murine
      model of asthma. METHODS: In the first phase of our study the animals received
      doses of 0.5MUg, 5MUg and 50MUg of OM-85 through gavage for five days (days -10
      to -6 of the protocol), 10 days prior to starting the sensitisation with
      ovalbumin (OVA), in order to evaluate the results of dose-response protocols. A
      single dose (5MUg) was then chosen in order to verify in detail the effect of OM
      85 on the pulmonary allergic response. Total/differential cells count and
      cytokine levels (IL-4, IL-5, IL-13 and IFN-gamma) from bronchoalveolar lavage
      fluid (BALF), OVA-specific IgE levels from serum, lung function and lung
      histopathological analysis were evaluated. RESULTS: OM-85 did not reduce
      pulmonary eosinophilic response, regardless of the dose used. In the phase
      protocol using 5MUg/animal of OM-85, no difference was shown among the groups
      studied, including total cell and eosinophil counts in BALF, serum OVA-specific
      IgE, lung histopathologic findings and lung resistance. However, OM-85 decreased
      IL-5 and IL-13 levels in BALF. CONCLUSIONS: OM-85, administered in early life in
      mice in human-equivalent doses, does not inhibit the development of allergic
      pulmonary response in mice.

PMID- 27707589
TI  - Future considerations for clinical dermatology in the setting of 21st century
      American policy reform: Accountable Care Organizations.
AB  - An Accountable Care Organization (ACO) is a network of providers that
      collaborates to manage care and is financially incentivized to realize cost
      savings while also optimizing standards of care. Since its introduction as part
      of the 2010 Patient Protection and Affordable Care Act, ACOs have grown to
      include 16% of Medicare beneficiaries and currently represent Medicare's largest
      payment initiative. Although ACOs are still in the pilot phase with multiple
      structural models being assessed, incentives are being introduced to encourage
      specialist participation, and dermatologists will have the opportunity to
      influence both the cost savings and quality standard aspects of these
      organizations. In this article, part of a health care policy series targeted to
      dermatologists, we review what an ACO is, its relevance to dermatologists, and
      essential factors to consider when joining and negotiating with an ACO.

PMID- 27707591
TI  - Impact of skin cancer screening and secondary prevention campaigns on skin cancer
      incidence and mortality: A systematic review.
AB  - BACKGROUND: Benefits of skin cancer screening remain controversial. OBJECTIVE: We
      sought to update evidence on the impact of skin cancer screening and secondary
      prevention campaigns on skin cancer incidence, mortality, stage-specific
      incidence, and interval cancers after negative screening. METHODS: We searched
      MEDLINE and EMBASE for studies published in English or German between January 1,
      2005, and February 4, 2015. Two reviewers independently performed study
      selection, data extraction, and critical appraisal. Results were described in a
      narrative synthesis. RESULTS: Of 2066 records identified in databases and 10
      records found by manual search, we included 15 articles. Overall, evidence
      suggests that with implementation of skin cancer screening, incidence of in situ
      and invasive skin cancer increased; increasing rates of thin and decreasing rates
      of thick melanoma were observed. After cessation of screening, invasive melanoma
      incidence decreased. A significant melanoma mortality reduction was shown in a
      German study; 2 other studies observed fewer deaths than expected. No study on
      interval cancers was identified. LIMITATIONS: Publication bias cannot be ruled
      out. Most studies are limited because of their ecological design. CONCLUSION:
      Large ecological studies, a cohort study, a case-control study, and a survey
      indicate benefits of skin cancer screening, but the evidence level is very low.

PMID- 27707590
TI  - Development and validation of a noninvasive 2-gene molecular assay for cutaneous
      melanoma.
AB  - BACKGROUND: Clinical and histopathologic assessment of pigmented skin lesions
      remains challenging even for experts. Differentiated and accurate noninvasive
      diagnostic modalities are highly desirable. OBJECTIVE: We sought to provide
      clinicians with such a tool. METHODS: A 2-gene classification method based on
      LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene
      expression was evaluated and validated in 555 pigmented lesions (157 training and
      398 validation samples) obtained noninvasively via adhesive patch biopsy. Results
      were compared with standard histopathologic assessment in lesions with a
      consensus diagnosis among 3 experienced dermatopathologists. RESULTS: In 398
      validation samples (87 melanomas and 311 nonmelanomas), LINC00518 and/or PRAME
      detection appropriately differentiated melanoma from nonmelanoma samples with a
      sensitivity of 91% and a specificity of 69%. We established LINC00518 and PRAME
      in both adhesive patch melanoma samples and underlying formalin fixed paraffin
      embedded (FFPE) samples of surgically excised primary melanomas and in melanoma
      lymph node metastases. LIMITATIONS: This technology cannot be used on mucous
      membranes, palms of hands, and soles of feet. CONCLUSIONS: This noninvasive 2
      gene pigmented lesion assay classifies pigmented lesions into melanoma and
      nonmelanoma groups and may serve as a tool to help with diagnostic challenges
      that may be inherently linked to the visual image and pattern recognition
      approach.

PMID- 27707592
TI  - Introducing the Group for Research of Policy Dynamics in Dermatology: "Future
      considerations for clinical dermatology in the setting of 21st century American
      policy reform" manuscript series.

PMID- 27707593
TI  - Secukinumab shows significant efficacy in palmoplantar psoriasis: Results from
      GESTURE, a randomized controlled trial.
AB  - BACKGROUND: Plaque psoriasis affecting palms and soles is disabling and often
      resistant to treatment. OBJECTIVE: Evaluate the efficacy and safety of
      secukinumab, an anti-interleukin 17A antibody, in subjects with palmoplantar
      psoriasis. METHODS: In this double-blinded, randomized controlled trial, 205
      subjects were randomized 1:1:1 to secukinumab 300 mg, 150 mg, or placebo. The
      primary endpoint was Palmoplantar Investigator's Global Assessment (ppIGA) 0
      (clear) or 1 (almost clear/minimal) response at week 16. RESULTS: At week 16, the
      percentage of subjects who achieved clear or almost clear palms and soles (or
      ppIGA 0/1) with secukinumab 300 mg (33.3%) and 150 mg (22.1%) was superior to the
      percentage achieved with placebo (1.5%, P < .001). Palmoplantar Psoriasis Area
      and Severity Index (ppPASI) was significantly reduced with secukinumab 300 mg (
      54.5%) and 150 mg (-35.3%) compared with placebo (-4.0%, P < .001). Dermatology
      Life Quality Index (DLQI) 0/1 responses from subjects in the secukinumab groups
      were also significantly higher compared with placebo at week 16 (P < .01) and
      pain and function of palms and soles was markedly improved with secukinumab as
      measured by the palmoplantar Quality-of-Life Instrument. Secukinumab 300 mg
      consistently showed the best outcomes. The safety profile was favorable and
      similar to previous studies. LIMITATIONS: Lack of active comparator. CONCLUSION:
      In GESTURE, the largest randomized controlled trial in palmoplantar psoriasis,
      secukinumab demonstrated the greatest efficacy to date for treating difficult-to
      treat psoriasis.

PMID- 27707594
TI  - The positive impact of radiologic imaging on high-stage cutaneous squamous cell
      carcinoma management.
AB  - BACKGROUND: There is limited evidence on the utility of radiologic imaging for
      prognostic staging of cutaneous squamous cell carcinoma (CSCC). OBJECTIVE: Review
      utilization of radiologic imaging of high-stage CSCCs to evaluate whether imaging
      impacted management and outcomes. METHODS: Tumors classified as Brigham and
      Women's Hospital (BWH) tumor (T) stage T2B or T3 over a 13-year period were
      reviewed to identify whether imaging was performed and whether results affected
      treatment. Disease-related outcomes (DRO: local recurrence, nodal metastasis,
      death from disease) were compared between patients by type of imaging used.
      RESULTS: 108 high-stage CSCCs in 98 patients were included. Imaging (mostly
      computed tomography, 79%) was utilized in 45 (46%) patients and management was
      altered in 16 (33%) patients who underwent imaging. Patients that received no
      imaging were at higher risk of developing nodal metastases (nonimaging, 30%;
      imaging, 13%; P = .041) and any DRO (nonimaging, 42%; imaging, 20%; P = .028)
      compared to the imaging group. Imaging was associated with a lower risk for DRO
      (subhazard ratio, 0.5; 95% CI 0.2-0.9; P = .046) adjusted for BWH T stage, sex,
      and location. LIMITATIONS: Single institution retrospective design and changes in
      technology overtime. CONCLUSIONS: Radiologic imaging of high-stage CSCC may
      influence management and appears to positively impact outcomes. Further
      prospective studies are needed to establish which patients benefit from imaging.

PMID- 27707596
TI  - Modifications of exposure to ambient particulate matter: Tackling bias in using
      ambient concentration as surrogate with particle infiltration factor and ambient
      exposure factor.
AB  - Numerous epidemiological studies explored health risks attributed to outdoor
      particle pollution. However, a number of these studies routinely utilized ambient
      concentration as a surrogate for personal exposure to ambient particles. This
      simplification ignored the difference between indoor and outdoor concentrations
      of outdoor originated particles and may bias the estimate of particle-health
      associations. Intending to avoid the bias, particle infiltration factor (Finf),
      which describes the penetration of outdoor particles in indoor environment, and
      ambient exposure factor (alpha), which represents the fraction of outdoor
      particles people are truly exposed to, are utilized as modification factors to
      modify outdoor particle concentration. In this study, the probabilistic
      distributions of annually-averaged and seasonally-averaged Finf and alpha were
      assessed for residences and residents in Beijing. Finf of a single residence and
      alpha of an individual was estimated based on the mechanisms governing particle
      outdoor-to-indoor migration and human time-activity pattern. With this as the
      core deterministic model, probabilistic distributions of Finf and alpha were
      estimated via Monte Carlo Simulation. Annually-averaged Finf of PM2.5 and PM10
      for residences in Beijing tended to be log-normally distributed as lnN(
      0.74,0.14) and lnN(-0.94,0.15) with geometric mean value as 0.47 and 0.39,
      respectively. Annually-averaged alpha of PM2.5 and PM10 for Beijing residents
      also tended to be log-normally distributed as lnN(-0.59,0.12) and lnN(-0.73,0.13)
      with geometric mean value as 0.55 and 0.48, respectively. As for seasonally
      averaged results, Finf and alpha of PM2.5 and PM10 were largest in summer and
      smallest in winter. The obvious difference between these modification factors and
      unity suggested that modifications of ambient particle concentration need to be
      considered in epidemiological studies to avoid misclassifications of personal
      exposure to ambient particles. Moreover, considering the inter-individual
      difference of Finf and alpha may lead to a brand new perspective of particle
      health associations in further epidemiological study.

PMID- 27707595
TI  - 5-Fr sheathless transradial cardiac catheterization using conventional catheters
      and balloon assisted tracking; a new approach to downsizing.
AB  - BACKGROUND: While the uptake of transradial access site is growing, there are
      concerns about associated radial injury. We report a feasibility study of a
      technique that enables both 5Fr diagnostic and PCI cases to be undertaken without
      an arterial sheath using conventional diagnostic and guide catheters with a
      modified balloon assisted tracking (BAT) technique. METHODS: We performed a
      prospective single center pilot study to assess the feasibility and effectiveness
      of sheathless radial artery access and BAT to perform coronary angiography and
      angioplasty using conventional 5 Fr diagnostic and guide catheters. We assessed
      for successful acquisition of good quality angiogram, completion of the
      angioplasty and access site complications. RESULTS: 5 Fr sheathless cardiac
      catheterization was undertaken in diagnostic (55%) and PCI cases (45%, all
      indications) in 60 consecutive patients (mean age 62.8+/-11.4years) using
      conventional catheters. The procedure was successfully performed via the radial
      artery using a sheathless technique with BAT in 93.3% of patients. All patients
      had a patent radial artery following removal of the Helix device and there were
      no recorded access site complications. CONCLUSIONS: Trans-radial cardiac
      catheterisation for diagnostic and PCI cases using 5F Sheathless catheters (whose
      outer diameter is smaller than a 3Fr introducer sheath) with BAT appears feasible
      and allows both cardiac catheterization for diagnostic and PCI indications to be
      undertaken safely using conventional catheters through the radial route, with
      high success rates.

PMID- 27707597
TI  - Patterns of domestic exposure to carbon monoxide and particulate matter in
      households using biomass fuel in Janakpur, Nepal.
AB  - Household Air Pollution (HAP) from biomass cooking fuels is a major cause of
      morbidity and mortality in low-income settings worldwide. In Nepal the use of
      open stoves with solid biomass fuels is the primary method of domestic cooking.
      To assess patterns of domestic air pollution we performed continuous measurement
      of carbon monoxide (CO) and particulate Matter (PM2.5) in 12 biomass fuel
      households in Janakpur, Nepal. We measured kitchen PM2.5 and CO concentrations at
      one-minute intervals for an approximately 48-h period using the TSI DustTrak II
      8530/SidePak AM510 (TSI Inc, St. Paul MN, USA) or EL-USB-CO data logger (Lascar
      Electronics, Erie PA, USA) respectively. We also obtained information regarding
      fuel, stove and kitchen characteristics and cooking activity patterns. Household
      cooking was performed in two daily sessions (median total duration 4 h) with
      diurnal variability in pollutant concentrations reflecting morning and evening
      cooking sessions and peak concentrations associated with fire-lighting. We
      observed a strong linear relationship between PM2.5 measurements obtained by co
      located photometric and gravimetric monitoring devices, providing local
      calibration factors of 4.9 (DustTrak) and 2.7 (SidePak). Overall 48-h average CO
      and PM2.5 concentrations were 5.4 (SD 4.3) ppm (12 households) and 417.6 (SD
      686.4) MUg/m3 (8 households), respectively, with higher average concentrations
      associated with cooking and heating activities. Overall average PM2.5
      concentrations and peak 1-h CO concentrations exceeded WHO Indoor Air Quality
      Guidelines. Average hourly PM2.5 and CO concentrations were moderately correlated
      (r = 0.52), suggesting that CO has limited utility as a proxy measure for PM2.5
      exposure assessment in this setting. Domestic indoor air quality levels
      associated with biomass fuel combustion in this region exceed WHO Indoor Air
      Quality standards and are in the hazardous range for human health.

PMID- 27707598
TI  - Treatment effects and genotoxicity relevance of the toxic organic pollutants in
      semi-coking wastewater by combined treatment process.
AB  - The removal effects of main toxic organic pollutants in semi-coking wastewater by
      combined treatment process were investigated, while the genotoxicity relevance of
      wastewater from different treatment units were monitored by using Vicia faba
      bioassays. Results showed that 37 kinds of toxic organic pollutants were detected
      in the crude sewage, most of them were removed by physicochemical pretreatment,
      and the total concentration of organic pollutants decreased from 4826 mg L-1 to
      546 mg L-1. After pretreatment, benzenes, phenols, quinolines and indoles in the
      wastewater were mainly removed by anaerobic/aerobic biodegradation, but the
      polycyclic aromatic hydrocarbons (PAHs) were removed mainly by advanced
      treatment, total concentration of toxic organic pollutants was lower than 0.5 mg
      L-1 in the effluent. Genotoxicity evaluation results showed that the wastewater
      from coagulating sedimentation unit or foregoing had significant mutagenic
      properties. However, the micronuclei (MN) frequency (0/00, which was calculated
      by observing 1000 cells) induced by wastewater after adsorption with modified
      coke was only 8.060/00, it was no significant difference compared with negative
      control (7.430/00). It could be concluded that the adsorption treatment was
      required for the safety of effluent, and the physicochemical-biochemical combined
      process in this study was suitable for high concentration semi-coking wastewater
      treatment.

PMID- 27707599
TI  - Occurrence and trophic magnification of polybrominated diphenyl ethers (PBDEs)
      and their methoxylated derivatives in freshwater fish from Dianshan Lake,
      Shanghai, China.
AB  - In this study, polybrominated diphenyl ethers (PBDEs) and methoxylated
      polybrominated diphenyl ethers (MeO-PBDEs) were analyzed in eleven freshwater
      fish species from Dianshan Lake, Shanghai, China. The highest concentrations of
      PBDEs and MeO-PBDEs were found in snakehead, with mean values of 38 ng g-1 lw and
      4.2 ng g-1 lw, respectively. BDE-47 was the predominant congener of PBDEs,
      followed by BDE-154. Congener pattern variation of PBDEs was observed among
      different fish species, implying differences in biotransformation potential among
      fish. Yellow catfish showed highest concentrations of BDE-99, -153 and -183,
      suggesting that it is more resistant to debromination than any other fish
      analyzed in the present study. Trophic magnification factors were in the range of
      1.35-1.81 for all the PBDE congeners, but not for 2'-MeO-BDE-68. Negative
      relationship was observed between PBDEs concentration and sample size (length and
      weight), indicating fish size dilution effect.

PMID- 27707600
TI  - Transfer of hexabromocyclododecane flame retardant isomers from captive American
      kestrel eggs to feathers and their association with thyroid hormones and growth.
AB  - Feathers are useful for monitoring contaminants in wild birds and are
      increasingly used to determine persistent organic pollutants. However, few
      studies have been conducted on birds with known exposure levels. We aimed to
      determine how well nestling feather concentrations reflect in ovo exposure to
      hexabromocyclododecane (alpha-, beta- and gamma-HBCDD), and to determine if
      feather concentrations are related to physiological biomarkers. Captive kestrels
      (n = 11) were exposed in ovo to maternally transferred HBCDD-isomers at
      concentrations of 127, 12 and 2 ng/g wet weight of alpha-, beta- and gamma-HBCDD
      (measured in sibling eggs), respectively, and compared to controls (n = 6).
      Nestling growth was monitored at 5 d intervals and circulating thyroid hormone
      concentrations assessed at d 20. Tail feathers were collected prior to the first
      molt and analyzed for HBCDD isomers. The mean SigmaHBCDD concentration in
      feathers was 2405 pg/g dry weight (in exposed birds) and alpha-, beta- and gamma
      HBCDD made up 32%, 13%, and 55%, respectively of the SigmaHBCDD concentrations.
      This isomer distribution deviated from the typical dominance of alpha-HBCDD
      reported in vertebrate samples. Exposed chicks had significantly higher feather
      concentrations of beta- and gamma-HBCDD compared with controls (p = 0.007 and p =
      0.001 respectively), while alpha-HBCDD concentrations did not differ between the
      two groups. Feather concentrations of alpha-HBCDD were best explained by egg
      concentrations of beta- or gamma-HBCDD concentrations (wi = 0.50, 0.30
      respectively), while feather concentrations of beta- and gamma-HBCDD were
      influenced by growth parameters (rectrix length: wi = 0.61; tibiotarsus length:
      wi = 0.28). These results suggest that feather alpha-HBCDD concentrations may
      reflect internal body burdens, whereas beta- and gamma-HBCDD may be subject to
      selective uptake. The alpha-HBCDD concentrations in the feathers were negatively
      associated with the ratio of plasma free triiodothyronine to free thyroxine
      (T3:T4; p = 0.020), demonstrating for the first time that feather concentrations
      may be used to model the effect of body burdens on physiological endpoints.

PMID- 27707601
TI  - The level of mercury contamination in mariculture sites at the estuary of Pearl
      River and the potential health risk.
AB  - In the present study, the Hg contamination in mariculture sites located at the
      estuary of Pearl River was to investigate with an attempt to analyse associated
      health risks of dietary exposure to both total mercury (THg) and methyl mercury
      (MeHg) in cultured fish and shellfish. The highest total mercury concentration
      (7.037 +/- 0.556 ng L-1) of seawater was observed at Zhuhai Estuary. The Hg
      concentrations of sediment in Guishan Island were significantly higher (p < 0.05)
      than in Daya Bay (away from the Pearl River). Besides, the both THg and MeHg
      levels in sediment at mariculture sites were higher (p < 0.05) than corresponding
      reference sites. It was attributed to the fact that mariculture activities
      increased Hg loading and promoted MeHg production. The vertical distribution of
      Hg in sediment cores demonstrated that mercury methylation mostly occurred at the
      sediment-water interface. Results of health risk assessments showed that fish
      consumption would impose a higher risk to children but less to adults, while
      shellfish produced in the studied area was safe for consumption.

PMID- 27707603
TI  - Recent progress on the discovery of antiamoebic agents.
AB  - A large number of protozoans infect humans but Entamoeba histolytica is the only
      organism responsible for causing amoebiasis, a deadly disease after malaria.
      Numerous heterocycle-based antiamoebic agents have been previously synthesized as
      E. histolytica inhibitors and while some of these agents have shown moderate
      activity, the search for a novel and ideal antiamoebic compound is still ongoing.
      In this digest Letter, we present the latest data on antiamoebic agents from 2011
      to 2016 based on the different classes of heterocyclic agents.

PMID- 27707602
TI  - Effects of mineral amendments on trace elements leaching from pre-treated marine
      sediment after simulated rainfall events.
AB  - Bauxite extraction by-products (red mud) were used to evaluate their potential
      ability to stabilize trace elements from dredged and aerated/humidified marine
      sediment. The investigated by-products were: bauxaline(r)(BX) that is a press
      filtered red mud; bauxsolTM(BS) that is a press-filtered red mud previously
      washed with excess of seawater, and gypsum neutralized bauxaline(r) (GBX). These
      materials were separately mixed to dredged composted sediment sample considering
      5% and 20% sediment: stabilizer ratios. For pilot experiments, rainfall events
      were regularly simulated for 3 months. Concentrations of As, Mo, Cd, Cr, Zn, Cu,
      and Ni were analyzed in collected leachates as well as toxicity. Results showed
      that Cd, Mo, Zn, and Cu were efficiently stabilized in the solid matrix when 20%
      of BX, BS, and GBX was applied. Consequently, toxicity of leachates was lower
      than for the untreated sediment, meaning that contaminants mobility was reduced.
      A 5% GBX was also efficient for Mo, Zn and Cu stabilization. In all scenarios, As
      stabilization was not improved. Compared to all other monitored elements, Mo
      mobility seemed to depend upon temperature-humidity conditions during pilot
      experiments suggesting the need of further investigations.

PMID- 27707604
TI  - Synthesis and biological evaluation of ricinoleic acid-based lipoamino acid
      derivatives.
AB  - A series of novel ricinoleic acid based lipoamino acid derivatives were
      synthesized from (Z)-methyl-12-aminooctadec-9-enoate and different l-amino acids
      (glycine, alanine, phenyl alanine, valine, leucine, isoleucine, proline and
      tryptophan). The structures of all the prepared compounds were characterized by
      1H NMR, 13C NMR and mass spectral studies. The title compounds were evaluated for
      their antimicrobial and anti-biofilm activities. Among all the derivatives,
      compound 7a (Z)-methyl-12-(2-aminoacetamido)octadec-9-enoate exhibited promising
      antibacterial activity (MIC, 3.9-7.8MUg/mL) and compounds 7b (Z)-methyl 12-(2
      aminopropanamido)octadec-9-enoate and 7g (Z)-methyl-12-(pyrrolidine-2
      carboxamido)octadec-9-enoate exhibited moderate activity (MIC, 7.8-31.2MUg/mL)
      selectively against four different Gram-positive bacterial strains such as
      Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, S. aureus MLS-16 MTCC
      2940, Micrococcus luteus MTCC 2470. These compounds also exhibited excellent
      antifungal activity against studied fungal strains. Further, the compounds 7a, 7b
      and 7g were also screened for anti-biofilm activity. Among these lipoamino acid
      derivatives, compound 7a exhibited good anti-biofilm activity (IC50, 1.9
      4.1MUg/mL) against four Gram-positive bacterial strains.

PMID- 27707606
TI  - Role of bilateral mandibular distraction for asymmetry due to unilateral
      ankylosis.

PMID- 27707605
TI  - Cyclic peptide-based potent and selective SIRT1/2 dual inhibitors harboring
      Nepsilon-thioacetyl-lysine.
AB  - In the current study, we discovered that several N-terminus-to-side chain cyclic
      tripeptides harboring the catalytic mechanism-based SIRT1/2/3 inhibitory warhead
      Nepsilon-thioacetyl-lysine at their central positions exhibited a comparably
      strong inhibition (nM level) against the SIRT1/2-catalyzed Nepsilon-acetyl-lysine
      deacetylation reactions. Their dual SIRT1/2 inhibitory action was also found to
      be stronger than that against SIRT3/5/6. Considering the previous demonstration
      that a SIRT1/2 dual inhibition could be instrumental in achieving an anti-cancer
      effect on those cancers retaining the wild-type tumor suppresser p53 protein,
      these compounds could be employed as leads for developing novel anti-cancer
      agents.

PMID- 27707607
TI  - Association between acute kidney injury and risk of Parkinson disease.
AB  - BACKGROUNDS: Worldwide, the incidence of acute kidney injury (AKI) has been
      increasing. However, information on the long-term incidence of Parkinson disease
      (PD) in patients with AKI has not been reported. METHODS: A total of 9380
      patients with AKI and 37,484 age- and sex-matched patients who did not have AKI
      were identified during 2003-2011. All patients were tracked until a diagnosis of
      PD, death, or the end of 2011. Cumulative incidences and hazard ratios (HRs) were
      calculated. RESULTS: The mean follow-up time for PD was 6.89 (SD=3.30) years in
      the AKI cohort and 6.78 (SD=3.29) years in the non-AKI cohort. The overall
      incidence densities of PD were significantly higher in the AKI cohort than in the
      non-AKI cohort (6.04 vs. 3.99/1000 person-years), with an adjusted HR of 1.47
      (95% confidence interval [CI]=1.18-1.83). Compared with the patients in the non
      AKI cohort aged <=64years, the relative risk (95% CI) of PD was 2.17 (1.12-4.18),
      14.1 (9.16-21.8), and 14.1 (8.43-23.6) for the patients in the AKI cohort aged
      <=64, 65-79, and >=80years, respectively. CONCLUSION: Patients with AKI were
      associated with a higher long-term risk of PD.

PMID- 27707609
TI  - The Treatment of Plasmodium knowlesi Malaria.
AB  - Plasmodium knowlesi occurs across Southeast Asia and is the most common cause of
      malaria in Malaysia. High parasitaemias can develop rapidly, and the risk of
      severe disease in adults is at least as high as in falciparum malaria. Prompt
      initiation of effective treatment is therefore essential. Intravenous artesunate
      is highly effective in severe knowlesi malaria and in those with moderately high
      parasitaemia but otherwise uncomplicated disease. Both chloroquine and
      artemisinin-combination therapy (ACT) are highly effective for uncomplicated
      knowlesi malaria, with faster parasite clearance times and lower anaemia rates
      with ACT. Given the difficulties with microscope diagnosis of P. knowlesi, a
      unified treatment strategy of ACT for all Plasmodium species is recommended in
      coendemic regions.

PMID- 27707608
TI  - CHA2DS2-VASc score and clinical outcomes of patients with acute coronary
      syndrome.
AB  - BACKGROUND: The CHA2DS2-VASc score has been recommended for the assessment of
      thromboembolic risk in patients with atrial fibrillation. HYPOTHESIS: The CHA2DS2
      VASc score may be associated with adverse outcomes in patients with ACS. METHODS:
      Included were patients with ACS enrolled in the Acute Coronary Syndrome Israeli
      biennial Surveys (ACSIS) during 2000-2013. Patients were divided into 4 groups
      according to their CHA2DS2-VASc score (0 or 1, 2 or 3, 4 or 5, and >5). The
      primary endpoint was 1-year all-cause mortality. RESULTS: The 13,422 patients had
      a mean age of 63.5+/-13years and included 25.8% females. Higher CHA2DS2-VASc
      score was associated with a significant increase in 1-year mortality. Patients
      with a CHA2DS2-VASc score >5 had the highest 1-year mortality risk that was 6
      fold higher compared to patients with a score of 0 to 1 (hazard ratio=6, 95%
      CI=4.1-8.8, p<0.0001). However, even an intermediate CHA2DS2-VASc score of 2-3
      was associated with a significant 2.6-fold increase in 1-year mortality. Patients
      with a higher CHA2DS2-VASc score were less frequently selected for an invasive
      strategy with an early coronary angiogram and subsequent angioplasty and were
      less commonly treated with the guideline-based medications. However, differences
      in outcomes remained significant following a multivariate analysis suggesting
      that these variations in therapy can only partially explain the differences in
      outcomes. CONCLUSIONS: Higher CHA2DS2-VASc score identifies high-risk patients
      that may be overlooked by existing scores. Further studies are needed in order to
      evaluate whether the CHA2DS2-VASc score may be used together with the GRACE score
      for an improved risk assessment of ACS patients.

PMID- 27707610
TI  - Aberrant expressions of stem cell factor/c-KIT in rat testis with varicocele.
AB  - BACKGROUND/PURPOSE: Varicocele (VC) is considered by the World Health
      Organization as the main cause of male infertility. Studies have shown that VC
      can affect spermatogenesis and then result in male infertility. But the exact
      mechanism by which VC affects spermatogenesis is still unclear. Stem cell factor
      (SCF) and c-KIT receptor are crucial molecules during spermatogenesis in testis.
      This study aims to investigate whether SCF/c-KIT signaling is involved in the
      pathophysiology of VC on spermatogenesis. METHODS: Rat models of VC were built (n
      = 13), and sham-operated rats were used as controls (n = 8). The seminiferous
      tubules of the testis were observed with hematoxylin and eosin staining,
      expression of SCF was analyzed via enzyme-linked immunosorbent assay and Western
      blot, and expression of c-KIT was assessed with Western blot and
      immunofluorescence. RESULTS: Compared with controls, the seminiferous epithelium
      was disorganized and had significantly fewer cells in the testes of rats with VC.
      Expression of SCF increased in testes of VC rats, while expression of c-KIT was
      decreased. CONCLUSION: These results suggest that sperm counts in seminiferous
      epithelium are affected by VC, and the SCF/c-KIT system is aberrantly expressed
      in VC testis, which could be involved in male infertility caused by VC.

PMID- 27707611
TI  - Assessment of serum trace elements and electrolytes in children with childhood
      and atypical autism.
AB  - The existing data demonstrate a significant interrelation between ASD and
      essential and toxic trace elements status of the organism. However, data on trace
      element homeostasis in particular ASD forms are insufficient. Therefore, the
      objective of the present study was to assess the level of trace elements and
      electrolytes in serum of children with childhood and atypical autism. A total of
      48 children with ASD (24 with childhood and 24 with atypical autism) and age- and
      sex-adjusted controls were examined. Serum trace elements and electrolytes were
      assessed using inductively-coupled plasma mass spectrometry. The obtained data
      demonstrate that children with ASD unspecified are characterized by significantly
      lower Ni, Cr, and Se levels as compared to the age- and sex-matched controls. At
      the same time, significantly decreased serum Ni and Se concentrations were
      detected in patients with childhood autism. In turn, children with atypical
      autism were characterized by more variable serum trace element spectrum. In
      particular, atypical autism is associated with lower serum Al, As, Ni, Cr, Mn,
      and Se levels in comparison to the control values. Moreover, Al and Mn
      concentration in this group was also lower than that in childhood autism
      patients. Generally, the obtained data demonstrate lower levels of both essential
      and toxic trace elements in atypical autism group, being indicative of profound
      alteration of trace elements metabolism. However, further detailed metabolic
      studies are required to reveal critical differences in metabolic pathways being
      responsible for difference in trace element status and clinical course of the
      disease.

PMID- 27707612
TI  - Prevalence of treatment-resistant hypertension and important associated factors
      results from the Swedish Primary Care Cardiovascular Database.
AB  - We aimed to describe the prevalence, treatment, and associated comorbidity of
      treatment-resistant hypertension (TRH). This registry-based cohort study from The
      Swedish Primary Care Cardiovascular Database assessed 53,090 hypertensive
      patients attending primary care. Patients adherent to antihypertensive treatment
      measured by pharmacy fills and with proportion of days covered >=80% were
      included. The prevalence of TRH was 17% when considering all current TRH
      definitions. Adherence to mineralocorticoid receptor antagonists differed between
      TRH- and non-TRH patients (8 vs. 4%). Higher frequencies (prevalence ratio and
      95% confidence intervals) of diabetes mellitus (1.59, 1.53-1.66), heart failure
      (1.55, 1.48-1.64), atrial fibrillation (1.33, 1.27-1.40), ischemic heart disease
      (1.25, 1.20-1.30), and chronic kidney disease (1.38, 1.23-1.54) were seen in
      patients with TRH compared to patients without TRH. These findings, in a
      population with valid data on medication adherence, emphasize a broad preventive
      approach for these high-risk patients.

PMID- 27707613
TI  - Post-traumatic transient cortical blindness in a child with occipital bone
      fracture.
AB  - Cortical blindness as sequelae of trauma has been reported in literature but
      mostly in the setting of occipital cortex or visual tract damages. We present a
      case of transient cortical blindness in a child following a closed head injury
      with a non-displaced occipital bone fracture and underlying occipital lobe
      contusion. We discuss the pathophysiology behind Post-traumatic transient
      cortical blindness, relevant investigations, and current management.

PMID- 27707614
TI  - Extreme lateral interbody fusion relieves symptoms of spinal stenosis and low
      grade spondylolisthesis by indirect decompression in complex patients.
AB  - Spinal stenosis and low-grade spondylolisthesis produce symptoms of neural
      compression that can be treated with extreme lateral lumbar interbody fusion
      (XLIF) via indirect decompression. This study aimed to investigate whether the
      restoration of disc dimensions would relieve symptoms of radiculopathy,
      claudication and back pain. In this retrospective study, patients undergoing XLIF
      surgery for relief of radicular symptoms or degenerative disc disease were
      included. Radiologically proven changes were used to assess the modes of
      degeneration. Objective measures such as the Visual Analogue Scale (VAS) for back
      and legs and the Oswestry Disability Index (ODI) were used. Complications were
      collated post-operatively from clinical notes and outpatient appointments. Twenty
      three consecutive patients were included, of whom 91% had spinal stenosis. The
      cohort presented with multiple comorbidities and 35% of the cohort had undergone
      previous lumbar surgery. There was a 61% improvement of coronal Cobb angle and an
      11% correction of the lordosis sustained 1year after surgery. Clinical outcomes
      at 1year showed 39%, 50% and 60% improvements in the ODI, back and leg VAS scores
      respectively. 48% of patients had reduced sensation related to lumbosacral plexus
      manipulation and one retroperitoneal haematoma was conservatively managed.
      Minimally invasive spinal (MIS) XLIF resulted in effective restoration of disc
      dimensions via indirect decompression, providing good relief of clinical symptoms
      evidenced by significant improvement in clinical outcome scores. XLIF corrected
      scoliosis and improved lumbar lordosis significantly. Several plexopathies did
      not hinder long-term recovery. XLIF is highly suited to treating complex patients
      with multiple comorbidities and degenerative disease.

PMID- 27707615
TI  - Prospective controlled cohort study of Troponin I levels in patients undergoing
      elective spine surgery for degenerative conditions: Prone versus supine position.
AB  - : Prior studies have suggested that elevated serum Troponin-I (TnI) levels
      immediately after non-cardiac surgical procedures (8-40%) represent subclinical
      cardiac stress which independently predicts increased 30-day mortality. Routine
      post-operative TnI monitoring has therefore been suggested as a standard of care.
      However, no prior studies have focussed on elective degenerative spine surgery,
      whilst few have measured pre-op TnI. Further, prolonged prone positioning could
      represent an additional, independent, cardiac stress. We planned a prospective
      controlled cohort study of consecutive TnI levels in routine elective spine
      surgery for degenerative spine conditions, incorporating 3 groups: 'prone<2h',
      'prone>2h' and 'supine' positioning. TnI levels (>0.04MUg/L) were recorded
      immediately pre-/post-surgery, and by 24h of surgery. N=120 patients were
      recruited. Complete results were obtained in 92 (39 supine, 53 prone). No
      significant between-groups differences were observed in demographic or
      cardiovascular risk factors. Validated TnI-elevation by 24h was not observed in
      any group. Spurious elevations were recorded in one 'prone<2h' and one
      'prone>2h'. One non-ST segment myocardial infarction (STEMI) occurred on day 7
      without TnI elevation by 24h (prone>2h). There was no 30-day mortality.
      CONCLUSIONS: Despite a lower cut-off, no validated TnI elevation was observed in
      any group by 24h after surgery. One non-STEMI had not been associated with TnI
      elevation by 24h. Immediately peri-operative cardiac stress therefore appeared
      comparatively rare in patients undergoing routine elective spine surgery.
      Further, prone positioning did not represent an additional, independent, risk.
      Routine immediately post-operative TnI monitoring in elective spine surgery
      therefore appears unjustified. Our study highlighted several caveats regarding
      consecutive TnI testing.

PMID- 27707616
TI  - Potential action of extract of Acmella oleracea (L.) R.K. Jansen to control
      Amblyomma cajennense (Fabricius, 1787) (Acari: Ixodidae) ticks.
AB  - The use of synthetic acaricides is currently the main method to control ticks.
      However, the indiscriminate use of these chemicals can lead to the selection of
      resistant individuals and in the accumulation of chemical residues in the
      environment, contaminating the soil and water streams, consequently affecting the
      flora, fauna, and the human beings as well. In this sense, the objective of this
      study was to investigate the acaricidal effect of crude ethanolic extract of
      Acmella oleracea (L.) R.K. Jansen aerials parts at different concentrations on
      fed males and semi-engorged females of A. cajennense s.s. An in vitro bioassay
      (Adult Immersion Test) was carried out to determine the lethal concentration 50
      (LC50) of ethanolic extract, calculated by Probit analysis. The results showed
      that the fed males were sensitive to all the concentrations of A. oleracea
      ethanolic extract, and mortality rate progressively increased (15-65%) in higher
      ethanolic extract concentrations. However, semi-engorged females were not
      sensitive to all the concentrations used here. In the highest concentration
      (100mg/mL), a mortality rate of 100% was observed after 72h of exposure,
      indicating that the acaricidal effect would probably be dose-dependent. The LC50
      values obtained for the fed A. cajennense s.s males and semi-engorged females
      were 29.4534mg/mL (limits: 24.4467-41.3847mg/mL) and LC50=17.6335mg/mL (limits:
      5.2506-23.5335mg/mL), respectively.

PMID- 27707617
TI  - Stenting versus endarterectomy after prior ipsilateral carotid endarterectomy.
AB  - BACKGROUND: Restenosis after carotid endarterectomy (CEA) is associated with an
      increased risk of stroke, and the management of critical or symptomatic
      restenotic lesions poses a treatment challenge. The superiority of CEA vs carotid
      angioplasty and stenting (CAS) for restenosis remains debatable because existing
      studies are few and limited by small sample size or the inability to align
      interventions with ipsilateral events beyond the periprocedural period. We
      performed a population-based evaluation of CEA vs CAS in a large contemporary
      cohort of patients with carotid artery restenosis. METHODS: We studied all
      patients in the Vascular Quality Initiative (VQI) database who underwent CEA or
      CAS after prior ipsilateral CEA between January 2003 and April 2015. Univariate
      methods (chi2 and t-test) were used to compare patients' characteristics and
      outcomes <=30 days and up to 1 year. Multivariate logistic and Cox regression
      analyses, adjusting for patients' demographic and clinical characteristics, were
      used to compare the procedures with respect to ipsilateral stroke, death,
      myocardial infarction (MI), stroke/death, and stroke/death/MI. RESULTS: This
      cohort of patients with prior ipsilateral CEA underwent 2863 carotid
      interventions, 1047 (37%) CEA, and 1816 (63%) CAS. Characteristics were similar
      in both groups. The 30-day ipsilateral stroke rate comparing CEA vs CAS was 2.2%
      vs 1.3% (P = .09) for asymptomatic patients and 1.2% vs 1.6% (P = .604) for
      symptomatic patients. The 30-day mortality was 1.3% vs 0.6% (P = .04), and MI
      occurred in 1.4% of CEA vs 1.1% of CAS patients (P = .443). Cranial nerve injury
      occurred in 4.1% of the redo-CEA cases, and access site complications occurred in
      5.3% of the CAS cases. CEA was associated with higher mortality at 30 days
      (adjusted odds ratio [aOR], 2.83; 95% confidence interval [CI], 1.13-7.14; P =
      .027) and at 1 year (adjusted hazard ratio, 2.17; 95% CI, 1.03-4.58; P = .042).
      However, there were no differences in postoperative stroke (aOR, 0.54; 95% CI,
      0.20-1.45, P = .22), MI (aOR, 0.98; 95% CI, 0.31-3.10; P = .97), stroke/death
      (aOR, 1.38; 95% CI, 0.72-2.67; P = .22), and stroke/death/MI (aOR, 1.38; 95% CI,
      0.80-2.37; P = .25) between CEA and CAS after adjusting for patient
      characteristics, and freedom from stroke at 1 year was also similar (CEA: 96.7%
      vs CAS: 96.4%; P = .78). CONCLUSIONS: In this population-based study, we have
      shown higher mortality but similar stroke and MI associated with redo CEA
      compared with CAS after prior ipsilateral CEA. We recommend avoidance of redo CEA
      in very sick patients. Smoking cessation remains a potent target for improvement
      of outcomes of carotid revascularization in these patients.

PMID- 27707618
TI  - Insight into the cerebral hyperperfusion syndrome following carotid
      endarterectomy from the national Vascular Quality Initiative.
AB  - BACKGROUND: Cerebral hyperperfusion syndrome (CHS), characterized by severe
      ipsilateral headache, seizures, and intracranial hemorrhage, is a rare, poorly
      understood complication that can be fatal following carotid endarterectomy (CEA).
      The purpose of the study was to determine the factors associated with CHS as
      captured in the Vascular Quality Initiative. METHODS: Analysis was conducted on
      51,001 procedures captured from the CEA module of the Vascular Quality Initiative
      from 2003 to 2015. Preoperative, operative, and postoperative variables were
      considered for inclusion in logistic regression analyses to determine possible
      associations with CHS. The relative contribution of each variable to the overall
      model was determined using dominance analysis. RESULTS: The mean age was 70.2 +/-
      9.4 years; there were 39.6% female patients, 93.1% of white race, with 29.6% of
      CEAs being performed for symptomatic status. The overall rate of CHS was 0.18% (n
      = 94), with 55.1% occurring in asymptomatic and 44.9% occurring in symptomatic
      patients with an associated mortality rate of 38.2%. Multivariable analysis
      including preoperative variables showed that female gender (odds ratio [OR],
      1.65; 95% confidence interval [CI], 1.09-2.51; P = .019), <1 month major
      ipsilateral stroke (OR, 5.36; 95% CI, 2.35-12.22; P < .001), coronary artery
      disease (OR, 1.77; 95% CI, 1.15-2.71; P = .009), and contralateral stenosis >=70%
      (OR, 1.54; 95% CI, 1.00-2.36; P = .050) were independently associated with CHS
      and that <1 month major stroke was the most important contributor to the model.
      With the additional inclusion of operative and postoperative variables, female
      gender (OR, 1.75; 95% CI, 1.14-2.67; P = .010), <1 month ipsilateral major stroke
      (OR, 3.20; 95% CI, 1.32-7.74; P = .010), urgency (OR, 2.25; 95% CI, 1.38-3.67; P
      = .001), re-exploration (OR, 2.98; 95% CI, 1.27-6.97; P = .012), postoperative
      hypertension (OR, 4.09; 95% CI, 2.65-6.32; P < .001), postoperative hypotension
      (OR, 3.21; 95% CI, 1.97-5.24; P < .001), dysrhythmias (OR, 3.23; 95% CI, 1.64
      6.38; P = .001), and postoperative myocardial infarction (OR, 2.84; 95% CI, 1.21
      6.67; P = .017) were significantly associated with CHS, with postoperative blood
      pressure lability and cardiac complications having the strongest associations
      with CHS. CONCLUSIONS: The risk of CHS was highest in female patients and in
      those with a recent major stroke, coronary artery disease, and contralateral
      stenosis >=70%. In addition, in adjusting for operative and postoperative
      variables, CHS was most significantly associated with postoperative blood
      pressure lability and cardiac complications. These data lend insight into a high
      risk population for this devastating complication.

PMID- 27707619
TI  - Single-center results of a series of prosthetic axillary-axillary arteriovenous
      access grafts for hemodialysis.
AB  - OBJECTIVE: Prosthetic infraclavicular axillary-axillary arteriovenous access
      grafts are one of a number of complex dialysis access options in patients when
      all of the usual upper limb possibilities have been exhausted. We present a
      follow-up of 35 patients who received this access graft during a 9-year period.
      METHODS: Patients were identified from our own operation records. Follow-up data
      were gathered from their locally held electronic medical records. Primary and
      secondary patency were calculated using the Kaplan-Meier estimate. RESULTS:
      During the study period, 15 of the 35 patients in our cohort underwent one or
      more revision operations. Primary patency was estimated at 88% at 6 months, and
      the secondary patency rate estimate was 54% at 48 months. Twelve patients died
      during the study period; the grafts in 17 of the 23 remaining patients were in
      use at the conclusion of the study. CONCLUSIONS: Although this is a small cohort,
      our results suggest that prosthetic axillary-axillary arteriovenous access should
      be at least considered as a viable long-term option for hemodialysis patients.

PMID- 27707620
TI  - Management of patients with acute aortic syndrome through a regional rapid
      transport system.
AB  - OBJECTIVE: The objective of this study was to describe the outcomes of patients
      with acute aortic syndrome (AAS) during and after transfer to a regional aortic
      center by a rapid transport system. METHODS: Review of patients with AAS who were
      transferred by a rapid transport system to a regional aortic center was
      performed. Data regarding demographics, diagnosis, comorbidities, transportation,
      and hospital course were acquired. Severity of existing comorbidities was
      determined by the Society for Vascular Surgery Comorbidity Severity Score
      (SVSCSS). The Acute Physiology and Chronic Health Evaluation II (APACHE II) score
      assessed physiologic instability on admission. Risk factors associated with
      system-related (transfer and hospital) mortality were identified by univariate
      and multivariate linear regression analysis. RESULTS: During a recent 18-month
      period (December 2013-July 2015), 183 patients were transferred by a rapid
      transport system; 148 (81%) patients were transported by ground and 35 (19%) by
      air. Median distance traveled was 24 miles (range, 3.6-316 miles); median
      transport time was 42 minutes (range, 10-144 minutes). Two patients died during
      transport, one with a type A dissection, the other of a ruptured abdominal aortic
      aneurysm. There were 118 (66%) patients who received operative intervention.
      Median time to operation was 6 hours. Type B dissections had the longest median
      time to operation, 45 hours, with system-related mortality of 1.9%; type A
      dissections had the shortest median time, 3 hours, and a system-related mortality
      of 16%. Overall, system-related mortality was 15%. On univariate analysis,
      factors associated with system-related mortality were age >=65 years (P = .026),
      coronary artery disease (P = .030), prior myocardial infarction (P = .049), prior
      coronary revascularization (P = .002), SVSCSS of >8 (P < .001), abdominal pain (P
      = .002), systolic blood pressure <90 mm Hg at sending hospital (P = .001),
      diagnosis of aortic aneurysm (P = .013), systolic blood pressure <90 mm Hg in the
      intensive care unit (P < .001), and APACHE II score >10 (P = .004). Distance
      traveled and transport mode and duration were not associated with increased risk
      of system-related mortality. Only SVSCSS of >8 (odds ratio, 7.73; 95% confidence
      interval, 2.32-25.8; P = .001) was independently associated with an increase in
      system-related mortality on multivariate analysis. CONCLUSIONS: Implementation of
      a rapid transport system, regardless of mode or distance, can facilitate
      effective transfer of patients with AAS to a regional aortic center. An SVSCSS of
      >8 predicted an increased system-related mortality and may be a useful metric to
      assess the appropriateness of patient transfer.

PMID- 27707622
TI  - Discussion.

PMID- 27707621
TI  - Predictors of intervention and mortality in patients with uncomplicated acute
      type B aortic dissection.
AB  - OBJECTIVE: Patients with uncomplicated acute type B aortic dissection (uATBAD)
      have historically been managed with medical therapy. Recent studies suggest that
      high-risk patients with uATBAD may benefit from thoracic endovascular aortic
      repair. This study aims to determine the predictors of intervention and mortality
      in patients with uATBAD. METHODS: All patients admitted with uATBAD from 2000 to
      2014 were reviewed, and those with computed tomographic angiography imaging were
      included. Multiplanar reconstruction was used to obtain double orthogonal oblique
      measurements. All measurements were obtained by a specialized cardiovascular
      radiologist (D.O.). The maximum aortic diameter, proximal descending thoracic
      aorta false lumen (FL) diameter, and area were recorded. Outcomes, including the
      need for intervention and mortality, were tracked over time. Data were analyzed
      by stratified Kaplan-Meier and multiple Cox regression analysis using SAS v 9.4
      (SAS Institute, Cary, NC). RESULTS: During the study period, 294 patients with
      uATBAD were admitted with 156 having admission computed tomographic angiography
      imaging available for analysis. The cohort had an average age of 60.6 years (+/
      13.6 years); 60% were males. The average follow-up time was 3.7 years
      (interquartile range, 2.1-6.9). A stratified analysis demonstrated the most
      sensitive cutoff for mortality was aortic diameter >44 mm (P < .01), and it
      appeared to be a threshold effect with minimal additional information added by
      finer size stratification. FL diameter did not predict mortality in our series (P
      = .36). Intervention-free survival, alternatively, appeared to decrease over the
      range of diameters from 35 to 44 mm (P < .01). An FL diameter >22 mm was
      associated with decreased intervention-free survival (P < .04). Age >60 years on
      admission also demonstrated decreased survival compared with those <=60 years of
      age (P < .01). Diameter >44 mm persisted as a risk factor for mortality (hazard
      ratio, 8.6; P < .01) after adjustment for diabetes (6.7; P < .01), age (1.06/y; P
      < .01), history of stroke (5.4; P < .01), connective tissue disorder (2.3; P <
      .01), and syncope on admission (9.5; P < .04). The 1-, 5-, and 10-year
      intervention rate for patients with admission aortic diameter >44 mm was 18.8%,
      29.5%, and 50.3%, respectively, compared with 4.8%, 13.3%, and 13.3% in the <=44
      mm group (P < .01). CONCLUSIONS: Aortic diameter >44 mm is a predictor of
      mortality after adjustment for other significant risk factors. Age >60 years on
      admission is a predictor of mortality. An FL diameter >22 mm as well as those
      with maximum aortic diameter >44 mm on admission were associated with decreased
      intervention-free survival. Patients with these high-risk criteria may benefit
      from thoracic endovascular aortic repair. Further studies are needed to further
      define those patients at highest risk and, thus, most likely to benefit from
      early intervention.

PMID- 27707623
TI  - Triethylated chromones with substituted naphthalenes as tubulin inhibitors.
AB  - Previously synthesized 2-(benzo[b]thiophene-3'-yl)-6,8,8-triethyldesmosdumotin B
      (1, TEDB-TB) and 2-(naphth-1'-yl)-6,8,8-triethyldesmosdumotin B (2) showed potent
      activity against multiple human tumor cell lines, including a multidrug-resistant
      (MDR) subline, by targeting spindle formation and/or the microtubule network.
      Consequently, ester analogues of hydroxylated naphthyl substituted TEBDs (3-5)
      were prepared and evaluated for their effects on tumor cell proliferation and on
      tubulin assembly. Among all new compounds, compound 6, a 4'-acetoxynaphthalen-1'
      yl derivative, displayed the most potent antiproliferative activity (IC50 0.2
      5.7MUM). Selected analogues were confirmed to be tubulin assembly inhibitors in
      cell-free and cell-based assays using MDR tumor cells. The new analogues
      partially inhibited colchicine binding to tubulin, suggesting their binding mode
      would be different from that of colchicine. This observation was supported by
      computational docking model analyses. Thus, the newly synthesized triethylated
      chromones with esterified naphthalene groups have good potential for development
      as a new class of mitotic inhibitors that target tubulin.

PMID- 27707624
TI  - Methylene versus carbonyl bridge in the structure of new tubulin polymerization
      inhibitors with tricyclic A-rings.
AB  - The phenothiazine group has been identified as a suitable A ring in the structure
      of tubulin polymerization inhibitors. In our search to identify more potent
      inhibitors, a study of different isosteric tricyclic groups as new potential A
      rings was first realized and permitted to identify 1-azaphenothiazine and
      iminodibenzyl as favorable modulations providing compounds with improved activity
      against tubulin. An investigation of the methylene group as the connector between
      the A and B rings revealed that the "CH2" bridge was tolerated, improving the
      biological potency when the A unit was of phenothiazine, 1-azaphenothiazine or
      iminodibenzyl type. Molecules 6-8 and 12 showed increased biological activity in
      comparison to parent phenstatin 2 on COLO 205 colon cancer cell line. The most
      antineoplastic agent in the current study was phenothiazine 5 displaying a GI50
      of 25nM against the melanoma MDA-MB-435 cell line.

PMID- 27707625
TI  - Synthesis and topoisomerases inhibitory activity of heteroaromatic chalcones.
AB  - The critical role of nuclear topoisomerase enzymes during cell proliferation
      process guided topoisomerases to be one of the major targets for anticancer drug
      development. We have designed and synthesized 22 heteroaromatic ring incorporated
      chalcone derivatives substituted with epoxide or thioepoxide. Topoisomerase
      enzyme inhibitory activity and cytotoxic tests were also conducted to evaluate
      compounds' pharmacological efficacy. In the topoisomerase I inhibitory test,
      compound 1 was most active one, 24% of inhibition at 20MUM, among all the
      compounds but it was lower than camptothecin. Compounds 9, 11, and 13 inhibited
      the function of topoisomerase II more strongly than etoposide with almost same
      magnitude (around 90% and 30% inhibition at 100 and 20MUM, respectively) which
      were higher than those of etoposide (72% and 18% inhibition). In the cytotoxicity
      test, compound 9 inhibited T47D cancer cell growth with the IC50 value of 6.61+/
      0.21MUM. On the other hand, compound 13 (IC50: 4.32+/-0.18MUM) effectively
      suppressed MDA-MB468 cancer cell growth.

PMID- 27707626
TI  - Inhibition of the metastatic progression of breast and colorectal cancer in vitro
      and in vivo in murine model by the oxidovanadium(IV) complex with luteolin.
AB  - The anticancer and antimetastatic behavior of the flavonoid luteolin and its
      oxidovanadium(IV) complex [VO(lut)(H2O)2]Na.3H2O (VOlut) has been investigated.
      Considering that the complex displayed strong anticancer activity on MDAMB231
      human breast cancer cell line we herein determined through in vitro assays that
      the complex would probably reduce breast cancer cell metastasis in a higher
      extent than the natural antioxidant. In the CT26 colon cancer cell line a
      stronger anticancer effect has also been determined for the complex (IC50 0.9MUM)
      and in addition it did not exert toxic effects on normal colon epithelial cells
      at concentrations up to 10MUM. Working with a murine model of highly aggressive,
      orthotopic colon cancer model (CT26 cancer cell lines) it has been determined
      that the complex might prevent metastatic dissemination of the colon cancer cells
      to the liver. The flavonoid luteolin also exerted anticancer effects (at a low
      degree, IC50 5.9MUM) on CT26 cell line and produced a 24% reduction of colon
      cancer liver metastasis.

PMID- 27707627
TI  - Sobetirome prodrug esters with enhanced blood-brain barrier permeability.
AB  - There is currently great interest in developing drugs that stimulate myelin
      repair for use in demyelinating diseases such as multiple sclerosis. Thyroid
      hormone plays a key role in stimulating myelination during development and also
      controls the expression of important genes involved in myelin repair in adults.
      Because endogenous thyroid hormone in excess lacks a generally useful therapeutic
      index, it is not used clinically for indications other than hormone replacement;
      however, selective thyromimetics such as sobetirome offer a therapeutic
      alternative. Sobetirome is the only clinical-stage thyromimetic that is known to
      cross the blood-brain-barrier (BBB) and we endeavored to increase the BBB
      permeability of sobetirome using a prodrug strategy. Ester prodrugs of sobetirome
      were prepared based on literature reports of improved BBB permeability with other
      carboxylic acid containing drugs and BBB permeability was assessed in vivo. One
      sobetirome prodrug, ethanolamine ester 11, was found to distribute more
      sobetirome to the brain compared to an equimolar peripheral dose of unmodified
      sobetirome. In addition to enhanced brain levels, prodrug 11 displayed lower
      sobetirome blood levels and a brain/serum ratio that was larger than that of
      unmodified sobetirome. Thus, these data indicate that an ester prodrug strategy
      applied to sobetirome can deliver increased concentrations of the active drug to
      the central nervous system (CNS), which may prove useful in the treatment of CNS
      disorders.

PMID- 27707629
TI  - Richter's Transformation in the Era of Kinase Inhibitor Therapy: A Review.
AB  - Richter's transformation (RT) is the transformation of chronic lymphocytic
      leukemia (CLL) into rapidly progressive B-cell lymphoma. This disease has long
      been recognized as a difficult-to-treat illness with poor survival outcomes.
      Although the incidence of RT has been well documented in previous studies, less
      is understood in the era of novel therapeutics, such as kinase inhibitors (KIs).
      The present review discusses the current risk factors, incidence, and outcomes of
      patients with RT in the modern era of KI therapy. Although the outcomes remain
      poor for RT patients after KI therapy, the most up-to-date studies have shown no
      increased incidence of RT in this patient population. Additionally, the present
      review reports the outcomes from the most recent data on novel therapies under
      investigation for patients with RT.

PMID- 27707628
TI  - Design, synthesis and evaluation of small molecule CD4-mimics as entry inhibitors
      possessing broad spectrum anti-HIV-1 activity.
AB  - Since our first discovery of a CD4-mimic, NBD-556, which targets the Phe43 cavity
      of HIV-1 gp120, we and other groups made considerable progress in designing new
      CD4-mimics with viral entry-antagonist property. In our continued effort to make
      further progress we have synthesized twenty five new analogs based on our earlier
      reported viral entry antagonist, NBD-11021. These compounds were tested first in
      HIV-1 Env-pseudovirus based single-cycle infection assay as well as in a multi
      cycle infection assay. Four of these new compounds showed much improved antiviral
      potency as well as cytotoxicity. We selected two of the best compounds 45A (NBD
      14009) and 46A (NBD-14010) to test against a panel of 51 Env-pseudotyped HIV-1
      representing diverse subtypes of clinical isolates. These compounds showed
      noticeable breadth of antiviral potency with IC50 of as low as 150nM. These
      compounds also inhibited cell-to-cell fusion and cell-to-cell HIV-1 transmission.
      The study is expected to pave the way of designing more potent and selective HIV
      1 entry inhibitors targeted to the Phe43 cavity of HIV-1 gp120.

PMID- 27707630
TI  - Phospholipase Cgamma in Toll-like receptor-mediated inflammation and innate
      immunity.
AB  - Among the phospholipase C (PLC) isoforms, PLCgamma not only has unique structural
      characteristics in terms of harboring SH2 and SH3 domains but also mediates
      growth factor-induced signaling pathways. PLCgamma isoforms are expressed in
      several innate immune cell types, including macrophages, natural killer cells,
      mast cells, and neutrophils. Stimulation of Fc receptor or integrin in innate
      immune cells induces PLCgamma activation, which leads to phosphoinositide
      hydrolysis and calcium increase. The products of PLCgamma activity mediate the
      innate immune response by regulating respiratory burst, phagocytosis, cell
      adhesion, and cell migration. PLCgamma also regulates the inflammatory response
      by affecting Toll-like receptor-mediated signaling. Here, we briefly review the
      current understanding of the functional role of PLCgamma in inflammation and
      innate immunity in some innate immune cell types.

PMID- 27707631
TI  - Stabilization exercise compared to general exercises or manual therapy for the
      management of low back pain: A systematic review and meta-analysis.
AB  - AIM: We performed a systematic review with a meta-analysis to examine the
      efficacy of stabilization exercises versus general exercises or manual therapy in
      patients with low back pain. DESIGN: We searched MEDLINE, Cochrane Controlled
      Trials, Scielo, and CINAHL (from the earliest date available to November 2014)
      for randomized controlled trials that examined the efficacy of stabilization
      exercises compared to general exercises or manual therapy on pain, disability,
      and function in patients with low back pain. Weighted mean differences (WMD) and
      95% confidence intervals were calculated. RESULTS: Eleven studies met the
      inclusion criteria (413 stabilization exercises patients, 297 general exercises
      patients, and 185 manual therapy patients). Stabilization exercises may provide
      greater benefit than general exercise for pain reduction and improvement in
      disability. Stabilization exercise improved pain with a WMD of -1.03 (95% CI: 
      1.29 to -0.27) and improved disability with a WMD of -5.41 (95% CI: -8.34 to 
      2.49). There were no significant differences in pain and disability scores among
      participants in the stabilization exercise group compared to those in the manual
      therapy group. CONCLUSIONS: Stabilization exercises were as efficacious as manual
      therapy in decreasing pain and disability and should be encouraged as part of
      musculoskeletal rehabilitation for low back pain.

PMID- 27707632
TI  - Zika virus: Endemic and epidemic ranges of Aedes mosquito transmission.
AB  - As evidence linking Zika virus with serious health complications strengthens,
      public health officials and clinicians worldwide need to know which locations are
      likely to be at risk for autochthonous Zika infections. We created risk maps for
      epidemic and endemic Aedes-borne Zika virus infections globally using a
      predictive analysis method that draws on temperature, precipitation, elevation,
      land cover, and population density variables to identify locations suitable for
      mosquito activity seasonally or year-round. Aedes mosquitoes capable of
      transmitting Zika and other viruses are likely to live year-round across many
      tropical areas in the Americas, Africa, and Asia. Our map provides an enhanced
      global projection of where vector control initiatives may be most valuable for
      reducing the risk of Zika virus and other Aedes-borne infections.

PMID- 27707634
TI  - Descending Thoracic Aorta Bi-femoral Bypass for Aortoiliac Disease in Patients
      with a Hostile Abdomen.

PMID- 27707633
TI  - Long-term Results of Inframalleolar Bypass for Critical Limb Ischaemia.
AB  - INTRODUCTION: As the population ages and the incidence of diabetes increases, the
      expected number of patients with critical limb ischaemia (CLI) requiring distal
      revascularization will remain high or even increase. The aim of this study was to
      investigate the long-term results of inframalleolar bypass. MATERIAL AND METHODS:
      A total of 352 inframalleolar bypasses for CLI performed between 2002 and 2013
      were included. Risk factors were evaluated and patency (both clinical and imaging
      based), leg salvage, survival, and amputation free survival (AFS) assessed.
      RESULTS: The median follow up was 30 months (mean 42 months, range 1-186 months).
      The median age of the study population was 73 years, and 67% of the patients were
      male. The incidence of diabetes was 69%. In the majority of cases (82%), the
      indication for bypass was an ulcer or gangrene, and the remaining 18% of the
      patients had rest pain. Primary, assisted primary, and secondary clinical patency
      was 71.2%, 76.5%, 81.0%, and 59.7%, 69.3%, and 70.7%, and 49.0%, 58.6%, and 68.4%
      at 1, 5, and 10 years, respectively. The last imaging based secondary patency at
      1, 5, and 10 years was 79.3%, 68.1%, and 62.8%, respectively. The popliteal
      artery as the inflow artery (n = 194) was associated with superior primary (p =
      .013), assisted primary (p = .028), and secondary patency (p = .014) when
      compared with bypasses originating from the femoral artery (n = 158). The leg
      salvage rate at 1, 5, and 10 years was 78.6%, 72.0%, and 67.2%, respectively. Leg
      salvage was equal in patients with and without diabetes (p = .460). The
      respective survival and AFS rates at 1, 5, and 10 years were 70.3%, 37.4%, and
      15.9%, and 58.4%, 29.8%, and 12.8%. CONCLUSION: Bypass to the foot arteries
      yielded excellent long-term patency, and good limb salvage can be achieved in
      both non-diabetic and diabetic patients.

PMID- 27707635
TI  - Commentary on 'Spiral Laminar Flow: A Survey of a Three-dimensional Arterial Flow
      Pattern in a Group of Volunteers'.

PMID- 27707636
TI  - Ablative fractional CO2 laser for burn scar reconstruction: An extensive
      subjective and objective short-term outcome analysis of a prospective treatment
      cohort.
AB  - BACKGROUND: The introduction of ablative fractional CO2 lasers (CO2-AFL) for burn
      scar management shows promising results. Whilst recent studies have focused on
      objective scar outcomes following CO2-AFL treatment, to date no data on patient
      subjective factors such as quality of life are available. METHODS: A prospective
      study was initiated to analyze the safety and efficacy of the CO2-AFL. Various
      objective and subjective outcome parameters were prospectively collected from the
      date of first consultation and follow-up following treatment. Objective factors
      include the Vancouver Scar Scale (VSS), the Patient and Observer Scar Assessment
      Scale (POSAS), and ultrasound measurements of the thickness of the scar.
      Subjective parameters included the assessment of neuropathic pain and pruritus,
      as well as the evaluation of improvement of quality of life following CO2-AFL
      with the Burns Specific Health Scale (BSHS-B). For treatment effect analysis,
      patients were stratified according to scar maturation status (> or <2 years after
      injury). RESULTS: 47 patients with 118 burn scars completed at least one
      treatment cycle. At a median of 55 days (IQR 32-74) after CO2-AFL treatment all
      analyzed objective parameters decreased significantly: intra-patient normalized
      scar thickness decreased from a median of 2.4mm to 1.9mm (p<0.001) with a
      concomitant VSS-drop from a median of 7 to 6 (p<0.001). The overall POSAS patient
      scale decreased from a median of 9 to 5 (p<0.001) with similar effects documented
      in POSAS observer scales. Both pain and pruritus showed significant reduction.
      Quality of life increased significantly by 15 points (median 120 to 135;
      p<0.001). All of the identified changes following CO2-AFL were equally
      significant irrespective of scar maturation status. CONCLUSION: Our preliminary
      results confirm significant improvement in thickness, texture, colour, and
      symptoms following treatment with CO2-AFL. Foremost, quality of life of patients
      with both immature and mature scars (up to 23 years after injury) improved
      significantly after just one treatment session. To our knowledge, this is the
      first study to document such holistic treatment effects in burn patients treated
      by CO2-AFL.

PMID- 27707637
TI  - Healing time and incidence of hypertrophic scarring in paediatric scalds.
AB  - INTRODUCTION: Scald burns, which heal in less than 14 days, are seen to be at low
      risk of hypertrophic scar (HTS) formation. Consequently surgery is usually
      reserved for scalds likely to take more than 14 days to heal. With the use of
      silver based dressings over the past few years, anecdotally, we have observed a
      tendency to improved healing of scalds with conservative management and reduced
      need for surgical intervention. We aimed to investigate the effect of overall
      healing time of paediatric scalds on HTS formation over a five-year period (2011
      15). METHODS: We retrospectively identified all new patients attending the Royal
      Children's Hospital (RCH) burns clinic from 31st January 2011-31st July 2015.
      Medical histories were reviewed for burns caused by scalds. Scar quality was
      determined from written records or clinical photographs. Patients were compared
      in groups based on healing time of <10 days, 10-14 days, 15-21 days, 22-30 days
      or >30 days. RESULTS: We studied 322 children, of which 52 (16.1%) developed HTS.
      There was a significantly higher incidence of HTS with increased time to healing
      (mean 34.5 days compared to 12.1 days, p<0.01). There were 25 patients that
      underwent surgical treatment with excision or debridement and split thickness
      skin graft of which 21 (84%) developed HTS. Grafting offered no benefit in HTS
      rate in the 22-30 days to heal group. CONCLUSIONS: Our study confirms that there
      is a link between prolonged healing time of scald wounds and HTS. The danger of
      slow healing for scarring despite grafting, suggests this operation should be
      performed earlier than current practice to allow complete healing in less than 3
      weeks.

PMID- 27707638
TI  - Simulation training in burns.

PMID- 27707639
TI  - Comparing acute burn treatment in Japan and Nepal.

PMID- 27707640
TI  - Comparison of three cooling methods for burn patients: A randomized clinical
      trial.
AB  - Tap water may not be readily available in numerous places as a first aid for
      burns and, therefore, tea tree oil products are recommended alternatives. Our aim
      in this study was to compare the cooling effects of three burn-cooling
      methodologies, running tap water, Burnshield(r), and Burn Cool Spray(r), and
      suggest indications for each cooling method. This randomized, controlled, study
      enrolled patients with burns who used the emergency service of Seoul Bestian
      Hospital from June 2015 to October 2015. The allocation of the cooling methods
      was randomly generated using a computer. We cooled the burn wounds by applying
      one of the three methods and measured the skin surface temperature and pain level
      using a visual analog scale (VAS) scoring. Ninety-six patients were enrolled in
      this study. The variability in the median(IQR) skin temperatures of the three
      groups was from 33.5 degrees C (31.5-35.0) to 28.7 degrees C (25.9-30.9), 33.8
      degrees C (32.0-35.4) to 33.2 degrees C (30.5-35.0), and 34.0 degrees C (32.0
      35.1) to 34.4 degrees C (32.7-35.6) for the tap water, Burn Cool Spray(r), and
      Burnshield(r), respectively. The variability of the mean VAS pain scores was 6.9
      to 4.8 (tap water), 5.6 to 4.5 (Burn Cool Spray(r)), and 5.5 to 3.3
      (Burnshield(r)). The reduction of skin surface temperature by tap water was
      significantly greater than that by the other two methods. All three methods
      reduced the VAS pain score after 20min of treatment (p<0.001). The tap water had
      a similar effect to that of the Burn Cool Spray(r) but significantly better than
      that of Burnshield(r). There was a significant difference in the skin surface
      temperature and VAS pain score reduction (p=0.014 and p=0.007, respectively)
      between the groups cooled by tap water below and above 24 degrees C. The patients
      who visited the center within 30min showed a significantly higher skin
      temperature than those who came after 30min did (p=0.033). Tap water and Burn
      Cool Spray(r) reduced the skin surface temperature, but the Burnshield(r)
      slightly increased it. All three cooling methods were effective in relieving
      pain. The temperature of the tap water used was related to the reduction in skin
      surface temperature and VAS pain score. The patients who visited the hospital
      within 30min of their burn accident needed a longer cooling time to attain a
      comparable skin surface temperature to those who visited after 30min.

PMID- 27707641
TI  - Early assessment and identification of posttraumatic stress disorder,
      satisfaction with appearance and coping in patients with burns.
AB  - BACKGROUND: The first year after severe burn is a psychologically challenging
      period for the patient. Patients may still struggle with burn-related physical
      and psychological problems such as posttraumatic stress disorder (PTSD) and body
      image dissatisfaction (BID). AIM: This study investigates the presence of PTSD,
      BID and coping, at three, six and twelve months after discharge for early
      identification of patients in need of focused support during rehabilitation.
      METHODS: Fifty-two adult patients with different degrees of burns were followed
      at three, six and twelve months after discharge and 36 patients completed all
      assessment points. A standardized clinical protocol was used for systematic
      assessment of PTSD (IES-R), BID (SWAP-Swe) and Coping (CBQ). The follow-up
      included an intervention with a burn nurse as a complement to the existing
      program. RESULTS: Approximately half of the patients had a risk of developing
      PTSD three months after discharge from hospital, and body image dissatisfaction
      was found to potentially predict risk of PTSD during follow-up. CONCLUSIONS: The
      findings suggest that it is important to include patients with less extensive
      burns in follow-up as this group is at risk of development of PTSD. Using
      standardized questionnaires in early follow-up along with assessment of body
      image dissatisfaction may facilitate detection of psychological problems.

PMID- 27707642
TI  - The effect of smoking status on burn inhalation injury mortality.
AB  - INTRODUCTION: Three factors that effect burn mortality are age, total body
      surface of burn (TBSA), and inhalation injury. Of the three, inhalation injury is
      the strongest predictor of mortality thus its inclusion in the revised Baux score
      (age+TBSA+17* (inhalation injury, 1=yes, 0=no)). However, the weighted
      contribution of specific comorbidities such as smoker status on mortality has
      traditionally not been accounted for nor studied in this subset of burn patients.
      We therefore sought to examine the impact of current tobacco and/or marijuana
      smoking in patients with inhalation injury. METHODS: A retrospective analysis of
      patients admitted to a regional burn center from 2002 to 2012. Independent
      variables analyzed included basic demographics, burn mechanism, presence of
      inhalation injury, TBSA, pre-existing comorbidities, and smoker status. Bivariate
      analysis was performed and logistic regression modeling using significant
      variables was utilized to estimate odds of mortality. RESULTS: There were a total
      of 7640 patients over the study period. 7% (n=580) of the burn cohort with
      inhalation injury were included in this study. In-hospital burn mortality for
      inhalation injury patients was 23%. Current smokers (20%) included cigarette
      smokers and marijuana users, 19% and 3%, respectively. Preexisting respiratory
      disease (17%) was present in 36% of smokers compared to 13% of non-smokers
      (p<0.001). Smokers had significantly lower mortality rate (9%) compared to non
      smokers (26%, p<0.01). The logistic regression model for mortality outcomes
      identified statistically four significant variables: age, TBSA, ethnicity, and
      smoker status (OR=0.41, 95% CI=0.18-0.93). Presence of comorbidities, including
      preexisting respiratory disease, was not significant. CONCLUSION: In the sub
      group of burn patients with inhalation injury, the odds of mortality
      significantly decreased in pre-existing smokers after adjusting for significant
      covariates. We postulate that an immune tolerance mechanism that modulates and
      diminishes the pro-inflammatory response confers a survival advantage in smokers
      after exposure to acute smoke inhalation injury. Future prospective studies in
      human and/or animal models are needed to confirm these findings.

PMID- 27707643
TI  - Outpatient workload in the NHS: A new challenge for the burn services?
AB  - The aim of this study was to evaluate the impact of outpatient care on activities
      at the Adults' Regional Burns Centre and the Children's Regional Burns Unit, Mid
      Yorkshire Hospitals NHS Trust UK, where outpatient and inpatient responsibilities
      are shared between the nursing staff. Data for all inpatient and outpatient
      interactions (all care related activities with the presence of a Registered Nurse
      (RN)) was collected prospectively by the attending RN for two consecutive months
      (October and November 2014). We also retrospectively collected data related to
      daily RN staffing levels, and Centre/Unit admissions and discharges. We compared
      our results with the staffing standard recommended by the National Burn Care
      Review 2001 and the National Burn Care Standards 2013. In the two months analysed
      we recorded a total number of 1232 interactions: 240 for the adult inpatient
      service, 385 for the adult outpatient service, 155 for the paediatric inpatient
      service, 452 for the paediatric outpatient service. Considering this burden and
      collating it with daily RN staffing levels, we highlighted an understaffing in
      42.6% (26/61) of the days for the Adult Regional Burn Centre and in 100% (61/61)
      of the days and nights for the Children Regional Burn Unit. The impact of
      outpatients on the activities of a Burns Centre/Unit is a factor that should be
      taken into account when evaluating staffing needs and planning services. This is
      a variable not currently considered in any guideline for safe staffing.

PMID- 27707644
TI  - Effect of acoustic parameters on the cavitation behavior of SonoVue microbubbles
      induced by pulsed ultrasound.
AB  - SonoVue microbubbles could serve as artificial nuclei for ultrasound-triggered
      stable and inertial cavitation, resulting in beneficial biological effects for
      future therapeutic applications. To optimize and control the use of the
      cavitation of SonoVue bubbles in therapy while ensuring safety, it is important
      to comprehensively understand the relationship between the acoustic parameters
      and the cavitation behavior of the SonoVue bubbles. An agarose-gel tissue phantom
      was fabricated to hold the SonoVue bubble suspension. 1-MHz transmitting
      transducer calibrated by a hydrophone was used to trigger the cavitation of
      SonoVue bubbles under different ultrasonic parameters (i.e., peak rarefactional
      pressure (PRP), pulse repetition frequency (PRF), and pulse duration (PD)).
      Another 7.5-MHz focused transducer was employed to passively receive acoustic
      signals from the exposed bubbles. The ultraharmonics and broadband intensities in
      the acoustic emission spectra were measured to quantify the extent of stable and
      inertial cavitation of SonoVue bubbles, respectively. We found that the onset of
      both stable and inertial cavitation exhibited a strong dependence on the PRP and
      PD and a relatively weak dependence on the PRF. Approximate 0.25MPa PRP with more
      than 20MUs PD was considered to be necessary for ultraharmonics emission of
      SonoVue bubbles, and obvious broadband signals started to appear when the PRP
      exceeded 0.40MPa. Moreover, the doses of stable and inertial cavitation varied
      with the PRP. The stable cavitation dose initially increased with increasing PRP,
      and then decreased rapidly after 0.5MPa. By contrast, the inertial cavitation
      dose continuously increased with increasing PRP. Finally, the doses of both
      stable and inertial cavitation were positively correlated with PRF and PD. These
      results could provide instructive information for optimizing future therapeutic
      applications of SonoVue bubbles.

PMID- 27707645
TI  - Ultrasound assisted citric acid mediated pectin extraction from industrial waste
      of Musa balbisiana.
AB  - The objectives of the present work are to extract pectin from industrial waste of
      Musa balbisiana by ultrasound assisted citric acid mediated extraction method and
      optimization was done through central composite statistical experimental design
      under response surface methodology. The outcomes of this study exhibited that,
      process variables (ultrasound power, pH and extraction time) had considerable
      influence on the pectin extraction. Second order mathematical equation was
      constructed to predict the data through regression analysis. The optimal
      extraction process condition was ultrasound power of 323w, pH of 3.2, extraction
      time of 27min and SL (solid-liquid) ratio of 1:15g/ml. The mean experimental
      yield of pectin (8.99+/-0.018%) was fine accord among predicted yield of pectin
      (9.02%).

PMID- 27707646
TI  - Ultrasound-assisted Fenton process using siderite nanoparticles prepared via
      planetary ball milling for removal of reactive yellow 81 in aqueous phase.
AB  - Nano-sized siderite was used as catalyst for the heterogeneous Fenton process
      combined with ultrasonic irradiation to degrade reactive yellow 81 (RY-81) in the
      aqueous phase. As the most efficient process, nano-sized siderite prepared via
      ball milling was chosen to carry out the experiments. 6h milled siderite at
      initial pH of 3.0 led to the highest removal efficiency of 92.09% within the
      reaction time of 30min. At a short reaction time of 20min, increasing siderite
      nanoparticles dosage from 0.3 to 0.75g/L resulted in increasing removal
      efficiency from 49.82 to 79.86%, respectively, while further increase in the
      dosage caused a substantial decrease in the efficiency. In the case of the effect
      of solute concentration, increasing the dye up to 400mg/L led to a significant
      decrease in the removal efficiency (65.77%). The presence of 0.01M Na2CO3 and
      C2H5OH significantly diminished the decolorization efficiency of RY-81 (<10%)
      with initial concentration of 100mg/L. The intermediates produced during the
      treatment process were also identified using GC-MS analysis. This research
      suggested that ball milled siderite is a potential catalyst for the efficient
      decolorization of textile effluents via ultrasound-assisted Fenton process.

PMID- 27707647
TI  - Sonochemical preparation of stable porous MnO2 and its application as an
      efficient electrocatalyst for oxygen reduction reaction.
AB  - Porous MnO2 as a non-noble metal oxygen reduction reaction (ORR) electrocatalyst
      was prepared by a simple sonochemical route. The as-prepared porous MnO2
      exhibited higher electrocatalytic activity, superior stability and better
      methanol tolerance than commercial Pt/C catalyst in alkaline media. Furthermore,
      the ORR proceeded via a nearly four-electron pathway. Cyclic voltammetry (CV) and
      rotating-disk electrode (RDE) measurements verified that the ORR enhancement was
      attributed to the porous structure and good dispersity, which facilitated
      sufficient transport of ions, electrons, O2 and other reactants in the process of
      ORR. The results indicated that a facile and feasible sonochemical route could be
      used to prepare highly active porous MnO2 electrocatalyst for ORR, which might be
      promising for direct methanol fuel cells.

PMID- 27707648
TI  - Comparison of patency rates and clinical impact of different reconstruction
      methods following portal/superior mesenteric vein resection during
      pancreatectomy.
AB  - INTRODUCTION: Few studies have compared patency rates of the different methods of
      venous reconstruction (VR) during a pancreatectomy. This study aimed to evaluate
      the patency rates and the clinical impact of various reconstruction methods.
      METHODS: For the meta-analysis, databases were systematically searched to
      identify studies reporting the outcomes of patients who underwent PVR/SMVR. For
      the retrospective study, clinical data were retrospectively analyzed from
      patients who underwent a pancreatectomy and VR between Feb. 2009 and Oct. 2015.
      Patency was assessed by CT and/or ultrasound. RESULTS: For the meta-analysis, the
      long-term patency rates of the primary repair group and the autologous graft
      group were significantly higher than that of the synthetic graft group. For the
      retrospective study, the reconstruction consisted of primary repair in 62 cases
      (89.8%) and synthetic grafting in 7 cases (10.1%). Synthetic grafting was more
      likely to cause acute thrombosis compared with primary repair for PVR/SMVR (85.7%
      versus 16.7%). Acute thrombosis was associated with decreased median survival (12
      versus 6 months) and increased hazard of death. Late thrombosis and stenosis were
      not associated with survival or serious clinical impact. Median survival for the
      primary repair group and the synthetic grafting group was 12 and 7 months,
      respectively. CONCLUSION: Primary repair following PVR/SMVR is preferred and can
      be achieved in most situations. Stenosis should be noted when with risk factors
      (long segmental and tension), but it produced little clinical impact. Synthetic
      grafting was associated with a higher thrombosis rate. Acute thrombosis is
      associated with increased mortality and decreased survival.

PMID- 27707649
TI  - Rosmarinic acid inhibits inflammation and angiogenesis of hepatocellular
      carcinoma by suppression of NF-kappaB signaling in H22 tumor-bearing mice.
AB  - The aim of this study was to explore the anti-tumor effect and therapeutic
      potential of rosmarinic acid (RA) in the treatment of hepatocellular carcinoma
      (HCC). RA at 75, 150 and 300 mg/kg was given to H22 tumor-bearing mice by
      intragastric administration once daily for 10 consecutive days. Levels of
      inflammatory and angiogenic factors, including interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), vascular
      endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta)
      were measured by enzyme linked immunosorbent assays (ELISA). Protein levels of
      phosphorylated NF-kappaB p65 and p65 were detected by western blot. mRNA level of
      NF-kappaB p65 was analyzed by qRT-PCR. The results showed that RA could
      effectively suppress tumor growth with fewer toxic effects by regulating the
      secretion of cytokines associated with inflammation and angiogenesis, and
      suppressing the expression of NF-kappaB p65 in the xenograft microenvironment.
      Our findings unveil the possible anti-tumor mechanisms of RA and support RA as a
      potential drug for the treatment of HCC.

PMID- 27707650
TI  - Dendritic cells tip the balance towards induction of regulatory T cells upon
      priming in experimental autoimmune encephalomyelitis.
AB  - Counter-balancing regulatory mechanisms, such as the induction of regulatory T
      cells (Treg), limit the effects of autoimmune attack in neuroinflammation.
      However, the role of dendritic cells (DCs) as the most powerful antigen
      presenting cells, which are intriguing therapeutic targets in this context, is
      not fully understood. Here, we demonstrate that conditional ablation of DCs
      during the priming phase of myelin-specific T cells in experimental autoimmune
      encephalomyelitis (EAE) selectively aborts inducible Treg (iTreg) induction,
      whereas generation of T helper (Th)1/17 cells is unaltered. DCs facilitate iTreg
      induction by creating a milieu with high levels of interleukin (IL)-2 due to a
      strong proliferative response. In the absence of DCs, B220+ B cells take over
      priming of Th17 cells in the place of antigen-presenting cells (APCs), but not
      the induction of iTreg, thus leading to unregulated, severe autoimmunity.

PMID- 27707651
TI  - Response to " Dementia and death: Separate sides of the same Atrial Fibrillation
      coin?"

PMID- 27707652
TI  - Bladder continent catheterizable conduit (the Mitrofanoff procedure): Long-term
      issues that should not be underestimated.
AB  - BACKGROUND: Effective bladder emptying by clean intermittent catheterization for
      children with severe bladder dysfunction is critical for renal preservation and
      social integration. Use of a continent catheterizable conduit (CCC) as urethral
      alternative procedure provides effective bladder drainage. However, it brings a
      substantive maintenance. METHODS: Retrospective review of the indications and
      long-term outcomes of 54 patients with a Mitrofanoff procedure in a single center
      over a 20-year period (1995-2015). RESULTS: Indications of CCC include 21
      neurogenic bladders, 12 patients with epispadias/exstrophy, 13 bladder outlet
      obstruction, 6 malignancies and 2 cloaca. Median age at surgery was 8.3years
      (4months-20years). The appendix was used in 76% of cases. Most frequently
      encountered complication was stomal stenosis (n=17/34, 50%), occurring at median
      time of 9months (2months-13years). The other complications were: leakage in 9
      (26.5%); conduit stricture in 5 (14.7%), angulation of the conduit in 2 (5.8%)
      and prolapse in one (3%). Operative revision was encountered by 33 (61%)
      patients, the majority in the first 2years. Median follow-up was 4.3years
      (3months-16years). CONCLUSIONS: CCC has a high incidence of complication. It has
      to be used only when the native urethra is not suitable for catheterization.
      Carers, patients and families must be prepared to deal with both the complexity
      of index conditions and the complications of this procedure.

PMID- 27707653
TI  - The impact of morbid obesity on solid organ injury in children using the ATOMAC
      protocol at a pediatric level I trauma center.
AB  - INTRODUCTION: Obesity is an epidemic in the pediatric population. Childhood
      obesity in trauma has been associated with increased incidence of long-bone
      fractures, longer ICU stays, and decreased closed head injuries. We investigated
      for differences in the likelihood of failure of non-operative management (NOM),
      and injury grade using a subset of a multi-institutional, prospective database of
      pediatric patients with solid organ injury (SOI). METHODS: We prospectively
      collected data on all pediatric patients (<18years) admitted for liver or splenic
      injury from September 2013 to January 2016. SOI was managed based upon the ATOMAC
      protocol. Obesity status was derived using CDC definitions; patients were
      categorized as non-obese (BMI <95th percentile) or obese (BMI >=95th percentile).
      The ISS, injury grade, and NOM failure rate were calculated among other data
      points. RESULTS: Of 1012 patients enrolled, 117 were identified as having data
      regarding BMI. Eighty-four percent of patients were non-obese; 16% were obese.
      The groups did not differ by age, sex, mechanism of injury, or associated
      injuries. There was no significant difference in the rate of failure of non
      operative management (8.2% versus 5.3%). Obesity was associated with higher
      likelihood of severe (grade 4 or 5) hepatic injury (36.8% versus 15.3%, P=0.048)
      but not a significant difference in likelihood of severe (grade 4 or 5) splenic
      injury (15.3% versus 10.5%, P=0.736). Obese patients had a higher mean ISS (22.5
      versus 16.1, P=0.021) and mean abdominal AIS (3.5 versus 2.9, P=0.024).
      CONCLUSION: Obesity is a risk factor for more severe abdominal injury,
      specifically liver injury, but without an associated increase in failure of NOM.
      This may be explained by the presence of hepatic steatosis making the liver more
      vulnerable to injury. A protocol based upon physiologic parameters was associated
      with a low rate of failure regardless of the pediatric obesity status. LEVEL OF
      EVIDENCE: Level II prognosis.

PMID- 27707654
TI  - Can IQ predict parent-reported behavioral and emotional problems in children with
      neurological deficiencies?
AB  - OBJECTIVE: The aim of the current study was to investigate whether total
      intelligence scores (FSIQ) and/or a discrepancy in intelligence can predict
      behavioral or emotional problems in children with neurological deficiencies.
      METHOD: The population consists of children with neurological deficiencies (N =
      610, ranging from 6 to 17 years), referred due to concerns on the (educational)
      development of the child to a tertiary outpatient clinic. All children were
      tested with the Dutch Wechsler Intelligence Scale for Children - third edition
      (WISC-III-NL). A VIQ-PIQ discrepancy score was calculated by subtracting the
      performance capacities of the verbal capacities. The effects of demographic
      variables, FSIQ, and the VIQ-PIQ discrepancy on two parent-rated questionnaires
      measuring behavior and emotions in children were analyzed with linear and
      logistic regression models. RESULTS AND CONCLUSION: The VIQ-PIQ discrepancy was
      not predictive of behavioral or emotional problems recorded on the above
      mentioned parent-rated questionnaires. The FSIQ score, age, and sex were
      predictive to some extent: increases in age and FSIQ led to a decrease of
      reported problems, and boys showed more problems than girls. Children with
      neurological deficiencies had on average significantly higher verbal capacities
      than performance capacities, in line with the neuropsychological principle that
      language survives brain damage whereas performance capacities are more affected.

PMID- 27707655
TI  - The juvenile head trauma syndrome - Deterioration after mild TBI: Diagnosis and
      clinical presentation at the Emergency Department.
AB  - BACKGROUND: Annually 14.000 children with traumatic brain injury (TBI) are
      admitted to the Emergency Department (ED) in the Netherlands. Presentation varies
      and a specific entity comprises the juvenile head trauma syndrome (JHTS) with
      secondary deterioration after a mild trauma. As outcome of JHTS can be fatal,
      early recognition is essential. AIM: To outline the epidemiology and clinical
      features of JHTS, in comparison to paediatric mild TBI patients without JHTS.
      METHODS: Retrospective study of 570 patients with mild TBI admitted to the ED of
      a level-one trauma centre from 2008 to 2014. Diagnosis of JHTS by experienced
      neurologists was compared with diagnosis by physicians at the ED. RESULTS:
      Physicians at the ED diagnosed JHTS more frequently (14%) compared to experienced
      neurologists (8%). JHTS occurred after a lucid interval varying from 5 to 225 min
      (mean 44 (SD 64)) with changes in consciousness. JHTS patients were younger
      compared to mild TBI patients (4.1 (SD 2.4) vs. 7.3 (SD 5.7), p < 0.01), (range:
      1-10 years). Falls occurred more often in JHTS (84% vs. 69%, p = 0.03) and at
      presentation, vomiting (42% vs. 22%, p < 0.01) and changed behaviour (29% vs. 1%,
      p = 0.03) were more present compared to the mild TBI group. CONCLUSION AND
      DISCUSSION: JHTS occurs more often in children up to 10 years with falls as major
      cause of injury. Clues for recognition of this syndrome comprise changes in
      consciousness and vomiting or changed behaviour on presentation at the ED. For
      clinical practice, these factors should guide the decision for hospital admission
      or discharge.

PMID- 27707656
TI  - The International Classification of Functioning (ICF) to evaluate deep brain
      stimulation neuromodulation in childhood dystonia-hyperkinesia informs future
      clinical & research priorities in a multidisciplinary model of care.
AB  - The multidisciplinary team (MDT) approach illustrates how motor classification
      systems, assessments and outcome measures currently available have been applied
      to a national cohort of children and young people with dystonia and other
      hyperkinetic movement disorders (HMD) particularly with a focus on dyskinetic
      cerebral palsy (CP). The paper is divided in 3 sections. Firstly, we describe the
      service model adopted by the Complex Motor Disorders Service (CMDS) at Evelina
      London Children's Hospital and King's College Hospital (ELCH-KCH) for deep brain
      stimulation. We describe lessons learnt from available dystonia studies and
      discuss/propose ways to measure DBS and other dystonia-related intervention
      outcomes. We aim to report on current available functional outcome measures as
      well as some impairment-based assessments that can encourage and generate
      discussion among movement disorders specialists of different backgrounds
      regarding choice of the most important areas to be measured after DBS and other
      interventions for dystonia management. Finally, some recommendations for multi
      centre collaboration in regards to functional clinical outcomes and research
      methodologies for dystonia-related interventions are proposed.

PMID- 27707657
TI  - The relationship of dystonia and choreoathetosis with activity, participation and
      quality of life in children and youth with dyskinetic cerebral palsy.
AB  - AIM: To relate dystonia and choreoathetosis with activity, participation and
      quality of life (QOL) in children and youth with dyskinetic Cerebral Palsy (CP).
      METHODS: Fifty-four participants with dyskinetic CP (mean age 14y6m, SD 4y2m,
      range 6-22y) were included. The Dyskinesia Impairment Scale (DIS) was used to
      evaluate dystonia and choreoathetosis. Activity, participation and quality of
      life (QOL) were assessed with the Gross Motor Function Measure (GMFM), the
      Functional Mobility Scale (FMS), the Jebsen-Taylor Hand Function Test (JTT), the
      ABILHAND-Kids Questionnaire (ABIL-K), the Life Habits Kids (LIFE-H) and the
      Quality of Life Questionnaire for children with CP (CP-QOL). Spearman's rank
      correlation coefficient (rs) was used to assess the relationship between the
      movement disorders and activity, participation and QOL measures. RESULTS:
      Significant negative correlations were found between dystonia and the activity
      scales with Spearman's rank correlation coefficient (rs) varying between -0.65
      (95% CI = -0.78 to -0.46) and -0.71 (95% CI = -0,82 to -0.55). Correlations were
      also found with the LIFE-H (rs = -0.43; 95%CI = -0.64 to -0.17) and the CP-QOL
      (rs = -0.32; 95%CI = -0.56 to -0.03). As far as choreoathetosis is concerned, no
      or only weak relationships were found with the activity, participation and
      quality of life scales. INTERPRETATION: This cross-sectional study is the first
      to examine the relationship of dystonia and choreoathetosis in dyskinetic CP with
      the level of activity, participation and QOL. The results revealed dystonia has a
      higher impact on activity, participation and quality of life than
      choreoathetosis. These findings seem to suggest it is necessary to first focus on
      dystonia reducing intervention strategies and secondly on choreoathetosis.

PMID- 27707658
TI  - Can digital reinvention of ecological monitoring remove barriers to its adoption
      by practitioners? A case study of deer management in Scotland.
AB  - Monitoring is one of the key tools employed to help understand the condition of
      the natural environment and inform the development of appropriate management
      actions. While international conventions encourage the use of standardised
      methods, the link between the information monitoring provides and local
      management needs is frequently overlooked. This problem is further exacerbated
      when monitoring is employed in areas where there are divergent interests among
      stakeholders in land use and management. Such problems are found in the
      management of wild deer across Scotland, where monitoring, in the form of habitat
      impact assessments, have been introduced as an innovation in sustainable deer
      management. However, the uptake of habitat impact assessments has been limited.
      We used deer management in Scotland as a case study to explore whether
      reinventing habitat impact assessments, and hosting the system on a familiar
      digital platform (a mobile phone) could help to remove perceived barriers to the
      implementation of assessments. Using the diffusion of innovations as a
      theoretical framework three sets of workshops were conducted with participants
      representing different stakeholder interests. While the proposed digital system
      did address perceived barriers to the conduct of habitat monitoring, in addition
      it revealed underlying concerns on the use and purpose of habitat monitoring as a
      tool in land management. Such concerns indicate friction between scientific and
      management perspectives, which need to be considered and addressed if monitoring
      is to become more widely acceptable as a tool to inform the management of natural
      resources.

PMID- 27707659
TI  - Precision Molecular Diagnosis Defines Specific Therapy in Combined
      Immunodeficiency with Megaloblastic Anemia Secondary to MTHFD1 Deficiency.
AB  - BACKGROUND: Methylenetetrahydrofolate dehydrogenase (MTHFD1) deficiency has
      recently been reported to cause a folate-responsive syndrome displaying a
      phenotype that includes megaloblastic anemia and severe combined
      immunodeficiency. OBJECTIVE: To describe our investigative approach to the
      molecular diagnosis and evaluation of immune dysfunction in a family with MTHFD1
      deficiency. METHODS: The methods used were exome sequencing and analysis of
      variants in genes involved in the folate metabolic pathway in a family with 2
      affected siblings. Routine laboratory and research data were analyzed to gain an
      in-depth understanding of innate, humoral, and cell-mediated immune function
      before and after folinic acid supplementation. RESULTS: Interrogation of exome
      data for concordant variants between the siblings in the genes involved in folate
      metabolic pathway identified a heterozygous mutation in exon 3 of the MTHFD1 gene
      that was shared with their mother. In view of highly suggestive phenotype, we
      extended our bioinformatics interrogation for structural variants in the MTHFD1
      gene by manual evaluation of the exome data for sequence depth coverage of all
      the exons. A deletion involving exon 13 that was shared with their father was
      identified. Routine laboratory data showed lymphopenia involving all subsets and
      poor response to vaccines. In vitro analysis of dendritic cell and lymphocyte
      function was comparable to that in healthy volunteers. Treatment with folinic
      acid led to immune reconstitution, enabling discontinuation of all prophylactic
      therapies. CONCLUSIONS: Exome sequencing demonstrated MTHFD1 deficiency as a
      novel cause of a combined immunodeficiency. Folinic acid was established as
      precision therapy to reverse the clinical and laboratory phenotype of this
      primary immunodeficiency.

PMID- 27707660
TI  - Determinants of Incomplete Asthma Control in Patients with Allergic Rhinitis and
      Asthma.
AB  - BACKGROUND: Characterizing associations between the upper and lower airways is
      important for asthma management. OBJECTIVES: This study aimed to assess the
      determinants of incomplete asthma control in patients with allergic rhinitis (AR)
      and asthma. METHODS: Multiple factors including age, sex, atopy, smoking history,
      medication use, Asthma Control Questionnaire (ACQ) score, FEV1, fraction of
      exhaled nitric oxide (Feno), and rhinitis questionnaire score were examined. AR
      was defined by rhinitis symptoms and the sensitization to inhaled allergens. ACQ
      was used to dichotomize the subjects into the incompletely controlled group (ACQ
      score >=0.75) and the well-controlled group. The factors that contribute to
      incomplete asthma control were assessed by a multivariate analysis. RESULTS: A
      total of 260 patients with AR and asthma were enrolled and 108 patients (42%)
      were classified as incomplete asthma control. The incompletely controlled group
      was older (P < .05), and had more airflow limitation, more airway inflammation,
      and more severe rhinitis symptoms (all P < .001). In contrast, the well
      controlled group was more likely to be taking nasal corticosteroids (NCSs) (P <
      .01). In a multivariate model adjusted by age, asthma treatment, airflow
      limitation, and Feno, persistence and severity of rhinitis (odds ratio [OR],
      2.57; 95% CI, 1.41-4.70, and OR, 2.00; 95% CI, 1.10-3.65) and nonuse of NCSs (OR,
      3.83; 95% CI, 1.50-9.81) were independently associated with incomplete asthma
      control. CONCLUSIONS: The persistence and severity of AR and the use of NCSs were
      associated with the level of asthma control in patients with AR and asthma.
      Further studies are required to determine whether appropriate treatment of
      rhinitis would improve asthma control.

PMID- 27707661
TI  - Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled
      Corticosteroid Responsiveness in Chronic Cough? A Systematic Review.
AB  - BACKGROUND: Fractional exhaled nitric oxide (Feno) is a safe and convenient test
      for assessing TH2 airway inflammation, which is potentially useful in the
      management of patients with chronic cough. OBJECTIVE: To summarize the current
      evidence on the diagnostic usefulness of Feno for predicting inhaled
      corticosteroid (ICS) responsiveness in patients with chronic cough. METHODS: A
      systematic literature review was conducted to identify articles published in peer
      reviewed journals up to February 2015, without language restriction. We included
      studies that reported the usefulness of Feno (index test) for predicting ICS
      responsiveness (reference standard) in patients with chronic cough (target
      condition). The data were extracted to construct a 2 * 2 accuracy table. Study
      quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2.
      RESULTS: We identified 5 original studies (2 prospective and 3 retrospective
      studies). We identified considerable heterogeneities in study design and outcome
      definitions, and thus were unable to perform a meta-analysis. The proportion of
      ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from
      53% to 90%, and from 63% to 97%, respectively. The reported area under the curve
      ranged from about 0.60 to 0.87; however, studies with a prospective design and a
      lower prevalence of asthma had lower area under the curve values. None measured
      placebo effects or objective cough frequency. CONCLUSIONS: We did not find strong
      evidence to support the use of Feno tests for predicting ICS responsiveness in
      chronic cough. Further studies need to have a randomized, placebo-controlled
      design, and should use validated measurement tools for cough. Standardization
      would facilitate the development of clinical evidence.

PMID- 27707663
TI  - An improved multi-objective optimization model for supporting reservoir operation
      of China's South-to-North Water Diversion Project.
AB  - An improved multi-objective optimization model based on goal programming (GP) for
      supporting reservoir operation was developed under inflow senarios of multiple
      runoff guarantee rates (i.e., 25%, 75%, perennial mean, and 95%) and ecological
      goals with the combination of steady- and pulse-state ecological water demands.
      Under these four scenarios, discharge flows of Danjingkou Reservoir would be
      358.40, 369.67, 268.91 and 98.14*108m3/a, and those at Taocha Canal headwork
      would be 104.61, 86.62, 95.08 and 64.00*108m3/a, respectively. The generated
      results for stream flows could successfully meet the predetermined operational
      goals for the project. Comparatively, under the scenario of 95% runoff guarantee
      rate, the obtained strategies could not satisfy the ecological water demands. The
      modeling results indicated that the capacity of water diversion and storage for
      Danjiangkou Reservoir would be enhanced due to the operation of the South-to
      North Water Diversion Project. The results showed the risks associated with
      possible flooding would be comparatively low under those four runoff guarantee
      rates. This represents the current priority for flood control in Danjiangkou
      Reservoir needs to be changed into multiple ones including ecological water
      supply, water transfer, as well as downstream water security maintenance.

PMID- 27707662
TI  - Dietary predictors of urinary cadmium among pregnant women and children.
AB  - BACKGROUND: Cadmium is a toxic metal with modifiable exposure sources including
      diet. In pregnant women and children, unique dietary habits may contribute to
      DCd, and the relationship of diet to overall cadmium exposure can depend on
      specific factors during these transitional time periods. OBJECTIVES: This study
      aimed to identify and quantify food sources of DCd, describe the distribution of
      UCd, and determine the relationship of DCd and intake of specific foods with UCd,
      stratified by maternal smoking history, among pregnant women and children in a
      well-characterized Mexico City birth cohort. METHODS: Our sample included 192
      pregnant women (third trimester) and 223 children (7-15years). DCd was calculated
      using FFQ and the U.S. TDS. We also measured UCd, maternal history of smoking,
      and additional covariates. RESULTS: Pregnant women and children had geometric
      mean UCd concentrations of 0.19+/-0.78MUg/L and 0.14+/-0.60MUg/L, respectively.
      On average, estimated daily DCd intake was 9.3+/-3.5MUg for women and 12.2+/
      5.4MUg for children. Adjusted linear regression models showed a positive
      association between DCd and UCd among women (p=0.03) and children (p=0.03)
      without a maternal history of smoking. Intake of fruit and vegetables among women
      and potato consumption among children were positively associated with UCd.
      CONCLUSIONS: Pregnant women and their children are exposed to cadmium at dietary
      and urinary levels similar to those previously reported. Higher estimated DCd for
      children than for women could be attributed to the different FFQs or related to
      dietary pattern changes between age groups. DCd contributed to UCd in those
      without a maternal smoking history.

PMID- 27707665
TI  - Are the Pyrenees a barrier for the transport of birch (Betula) pollen from
      Central Europe to the Iberian Peninsula?
AB  - This work provides a first assessment of the possible barrier effect of the
      Pyrenees on the atmospheric transport of airborne pollen from Europe to the North
      of the Iberian Peninsula. Aerobiological data recorded in three Spanish stations
      located at the eastern, central and western base of the Pyrenees in the period
      2004-2014 have been used to identify the possible long range transport episodes
      of Betula pollen. The atmospheric transport routes and the origin regions have
      been established by means of trajectory analysis and a source receptor model.
      Betula pollen outbreaks were associated with the meteorological scenario
      characterized by the presence of a high-pressure system overm over Morocco and
      Southern Iberian Peninsula. France and Central Europe have been identified as the
      probable source areas of Betula pollen that arrives to Northern Spain. However,
      the specific source areas are mainly determined by the particular prevailing
      atmospheric circulation of each location. Finally, the Weather Research and
      Forecasting model highlighted the effect of the orography on the atmospheric
      transport patterns, showing paths through the western and easternmost lowlands
      for Vitoria-Gasteiz and Bellaterra respectively, and the direct impact of air
      flows over Vielha through the Garona valley.

PMID- 27707664
TI  - Seasonal effects to metallothionein responses to metal exposure in a naturalised
      population of Ruditapes philippinarum in a semi-enclosed estuarine environment.
AB  - The Manila clam (Ruditapes philippinarum), an invasive species in Northern
      Europe, can be used as a bioindicator of metal pollution. Seasonal effects on
      metallothionein (MT) production have not been considered in this species at the
      northernmost extent of its European distribution. This study assesses the annual
      seasonal effects on MT and metal concentrations in R. philippinarum from Poole
      Harbour, UK. R. philippinarum were collected in winter, spring, summer, and
      autumn throughout 2015, and MT and metal concentrations, as well as biotic and
      abiotic variables, were quantified. During winter, linear regression analysis
      showed significant positive relationships between tissue metal and MT
      concentrations. However, during spring and summer, these relationships were
      mostly insignificant. MT concentrations during spring had significant positive
      relationships with tissue and whole weight. Significant positive relationships
      were also observed between MT and condition index, during summer. During spring
      and summer, biotic factors seem to override the role of MT as a detoxification
      mechanism for metal exposure in this species. This is probably due to an increase
      in MT concentration in spring caused by gametogenesis, associated with increased
      tissue weight as the gonads expand. A depletion of energy resources, or physical
      stressors such as heat, may be attributed to the reduced MT production in clams
      of poor body condition in summer. The evidence from this study suggests that MT
      may only be a useful biomarker of metal pollution during winter in R.
      philippinarum in the UK. This verifies the natural variability of MT in this
      species at high latitudes, and highlights the potential and limits to a widely
      available bioindicator of metal pollution.

PMID- 27707666
TI  - Dissolved reactive phosphorus played a limited role in phosphorus transport via
      runoff, throughflow and leaching on contrasting cropping soils from southwest
      Australia.
AB  - PURPOSE: Phosphorus (P) lost from agricultural land by erosion, runoff,
      throughflow and leaching is of major concern for water resource managers
      worldwide. Previous study on soils from cropping land of southwest Western
      Australia suggested P loss as dissolved unreactive P (DURP) via leaching, but the
      implications for processes and rates of P transport in soils are not known.
      MATERIAL AND METHODS: Two contrasting soil profiles (sand and loam) from cropping
      land of southwest Western Australia were exposed to artificial rain in packed
      boxes and field runoff plots to examine P forms and fluxes in runoff,
      throughflow, leachate and soil solution after three P rates of application
      (equivalent to 0, 20 and 40kg P/ha). Solutions were analyzed for total P (TP),
      dissolved reactive P (DRP) and total dissolved P (TDP). Particulate P (PP) and
      DURP were calculated by subtracting DRP from TP and TDP respectively. RESULT AND
      DISCUSSION: In the sand profile, about 90% or more of P losses via runoff and
      leachate were in DURP and PP forms, whereas DRP was a minor contributor.
      Phosphorus load in soil solution, throughflow, leachate and run-off increased
      with increasing P rate. The relatively higher affinity of soil for DRP compared
      to DURP might cause the latter to be more mobile through profile in association
      with colloidal compounds <0.2MUm. Higher PP concentration for loam soil via
      throughflow is exacerbated by dispersed clay, which could be an additional
      process influencing P mobility in loam and duplex soils. CONCLUSION: The DRP
      played a limited role in P transport compared to PP and DURP that both appeared
      to be associated with soil particles or soil colloids in runoff, throughflow,
      leachate and soil solution. Further characterization of the latter forms of P is
      needed so that management practices can be developed to minimize P losses.

PMID- 27707667
TI  - Fractionation of radiocesium in soil, sediments, and aquatic organisms in Lake
      Onuma of Mt. Akagi, Gunma Prefecture using sequential extraction.
AB  - The Fukushima Daiichi Nuclear Power Plant (FDNPP) accident has resulted in the
      contamination of the environment in Gunma Prefecture with radioisotope cesium
      (radio-Cs, 134Cs and 137Cs). Concentrations of radio-Cs >500Bqkg-1 were found in
      wakasagi (Hypomesus nipponensis) in Lake Onuma at the top of Mount (Mt.) Akagi in
      August 2011. To explain the mechanism of this contamination, monitoring studies
      have been conducted around Lake Onuma by measuring radio-Cs concentrations in
      samples of fish, aquatic plants, plankton, lake water, lake sediments, and
      surrounding soil. The leachability of radio-Cs was evaluated using sequential
      extraction by Tessier et al. The total concentration of radio-Cs in Lake Onuma
      ecosystems decreased gradually with time. In the brown forest soil, radio-Cs
      concentrations of 2000 to 6000Bqkg-1 were detected. The abundance ratio of the
      easy-elution form (exchangeable and carbonate forms) in the samples was <10%. The
      concentrations in phytoplankton samples were 3-6 times higher than those in
      wakasagi samples. The ratios of easy-elution forms increased by the rank in the
      food chain; 37% in phytoplankton, 78% in zooplankton, and 97% in wakasagi. It is
      likely that the lower ratio of the easy-elution form in phytoplankton is related
      to the adsorption of radio-Cs on suspended substances in the lake, as suggested
      by the analyses of aluminum and titanium in the phytoplankton, zooplankton, and
      wakasagi samples. The high concentrations of radio-Cs in wakasagi would be
      related also to the characteristics of closed mountain lakes.

PMID- 27707668
TI  - A case of tricuspid valve endocarditis due to Cardiobacterium hominis which
      emphasizes the shift between the poverty of clinical symptoms and the severity of
      cardiac damages.
AB  - Infectious endocarditis due to Cardiobacterium hominis is an uncommon event,
      accounting for less than 2% of all cases of infectious endocarditis. The
      infection of the tricuspid valve as it is reported here is extremely rare. We
      report the case of a tricuspid endocarditis due to Cardiobacterium hominis in a
      56 year-old man who was admitted to hospital with pelvic and scapular pain. The
      diagnosis was established through positive blood cultures and echographic
      detection of a large tricuspid vegetation. Despite efficient antibiotic therapy,
      valve replacement was required. The clinical course of Cardiobacterium
      endocarditis is usually subacute, and the diagnosis may therefore be delayed.
      This case emphasizes the shift between the poverty of clinical symptoms and
      severity of cardiac damages, what we could call the Cardiobacterium paradox.

PMID- 27707669
TI  - Bilateral symmetric transposition flap (pincer flap) for reconstruction of a 19
      cm2 defect of the forehead.

PMID- 27707670
TI  - Pustulosis acuta generalisata with mucosal and joint involvement associated with
      polyspecific autoantibodies.

PMID- 27707671
TI  - Cytogenetics in the management of children and adult acute lymphoblastic leukemia
      (ALL): an update by the Groupe francophone de cytogenetique hematologique (GFCH).
AB  - Cytogenetic analyses (karyotype and, if necessary, appropriate complementary FISH
      analyses) are mandatory at diagnosis in acute lymphoblastic leukemia (ALL) as
      their results are taken into account in therapeutic protocols due to their
      diagnostic and prognostic values. In some cases, karyotype can be completed by
      other techniques (RT-PCR, RQ-PCR, DNA content, SNP-array, MLPA...) that can be
      equally or more informative than FISH. Here, we have tempted to establish
      guidelines concerning karyotype and FISH analyses according to the most recent
      data of the litterature which is reviewed here, completing the 2008 WHO
      classification with the recent new cytogenomic entities such as Ph-like ALL and
      indicating possible therapeutic implications.

PMID- 27707672
TI  - Cytogenetics in the management of lymphomas and lymphoproliferative disorders in
      adults and children: an update by the Groupe francophone de cytogenetique
      hematologique (GFCH).
AB  - Non-Hodgkin's lymphomas and lymphoproliferative disorders include a high number
      of heterogeneous entities, described in the 2008 WHO classification. This
      classification reflects the crucial role of a multidisciplinary approach which
      integrates cytogenetic results both for the notion of clonality and for
      differential diagnosis between these entities. The prognostic impact of some
      cytogenetic abnormalities or genome complexity is also confirmed for many of
      these entities. Novel provisional entities have been described, such as BCLU (B
      cell lymphoma unclassifiable with features intermediate between diffuse large B
      cell lymphoma and Burkitt lymphoma) for which karyotype is critical to
      distinguish BCLU from Burkitt's lymphoma. The karyotype can be established from
      any tumour or liquid infiltrated by lymphoma cells. Recent adaptations of
      technics for cellular cultures according to the subtype of known (or suspected)
      lymphoma have significantly improved the percentage of informative karyotypes.
      Conventional karyotypes remain the best technical approach recommended for most
      of these subtypes. Interphase and/or metaphase FISH also represents a solid and
      rapid approach, because of the significant number of recurrent (sometimes
      specific) rearrangements of these entities. Next generation sequencing
      technologies contribute to enrich genomic data and substantially improve the
      understanding of oncogenic mechanisms underlying these lymphoid malignancies.
      Some molecular biomarkers are already part of the diagnostic process (for
      example, somatic mutation of MYD88 in Waldenstrom disease) thus reinforcing the
      essential principle of a multidisciplinary approach for the diagnosis of all the
      mature lymphoid malignancies.

PMID- 27707673
TI  - Cytogenetics in the management of multiple myeloma: an update by the Groupe
      francophone de cytogenetique hematologique (GFCH).
AB  - Cytogenetics of multiple myeloma has evolved in recent years by the emergence of
      Interphasic fluorescence in situ hybridization (FISH) performed on sorted plasma
      cells detecting abnormalities independently of a proliferative and infiltrative
      index. Cytogenetic analysis plays a major part in the risk stratification of
      myeloma diagnosis due to prognostic impact of various cytogenetic abnormalities
      as well as to the association between emerging therapeutic approaches in MM.
      Thus, practice guidelines now recommend interphasic FISH or alternative molecular
      technics as the initial analysis for multiple myeloma. The Groupe francophone de
      cytogenetique hematologique (GFCH) proposes in this issue an update of managing
      multiple myeloma cytogenetics.

PMID- 27707674
TI  - Benefits of new immunoglobulin-derived biomarkers for the diagnosis and follow-up
      of patients with dysglobulinemia.
AB  - The diagnostics and follow-up of monoclonal gammopathies such as multiple myeloma
      require precise analysis of the monoclonal component as well as the other
      immunoglobulins isotypes, which might be limited by the sensitivity of standard
      laboratory methods. New serum biomarkers were developed for routine practice in
      the last decades, such as the free light chain assays and more recently the
      heavy/light chain assay<strike>s</strike>. Studies have shown that serum free
      light chain measurement was useful in the identification and follow-up of pauci
      or nonsecretory myeloma, free light-chain multiple myeloma and AL amyloidosis. It
      is also an important prognostic marker for monoclonal gammopathy of undetermined
      significance and AL amyloidosis progression. Hevylite method enables quantitative
      analysis of heavy/light chain pairs of IgG, IgA and IgM immunoglobulins. This
      technique has a promising potential to enrich the standard analytic tools as it
      enables to assess the concentration and ratio of the levels of both tumor and
      physiological immunoglobulins (heavy/light chain pair suppression), which is not
      possible with serum protein electrophoresis or global quantitative analysis of
      immunoglobulin isotypes. This review includes the latest International myeloma
      working group recommendations and key data presented at the Euromedlab convention
      in June 2015 Paris regarding serum free light chain and heavy/light chain assays
      in the biological monitoring of dysglobulinemia.

PMID- 27707675
TI  - Serum proteomic signatures as biomarkers of primary biliary cirrhosis diagnosis
      and prognosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease considered
      as an autoimmune disease. To identify new biomarkers of PBC, serum profiling
      analysis using Surface-enhanced laser desorption/ionization time-of-flight mass
      spectrometry (SELDI-TOF-MS) was employed. Twelve patients with either
      asymptomatic PBC (group 1, n=6) or PBC with a poor response to UDCA (group 2,
      n=6), were compared to healthy controls (group 3, n=6). Analysing the 18 sera by
      using four SELDI-TOF arrays under various conditions, we found four biomarkers of
      PBC at 5.9, 8.6, 8.9 and 9.0 kDa. The combination of the two arrays IMAC-40/Zn2+
      and CM-10/pH 7 improved the positive diagnosis of this disease. We also found a
      biomarker of severity of PBC at 95.2 kDa on LSAX-30 array which characterized
      patients with a bad prognosis. In conclusion, our study identified several serum
      proteomics signatures as potential biomarkers of PBC for its diagnosis or
      prognosis.

PMID- 27707676
TI  - Erysipelothrix rhusiopathiae bacteremia: a challenging diagnosis!
AB  - Erysipelothrix rhusiopathiae, a Gram-positive bacillus, is reported to cause for
      cutaneous infections and endocarditis. We report a case of E. rhusiopathiae
      bacteremia without severe clinical illness. The patient, a 74-year-old man, is
      suffering from a chronic lymphoid leukemia (LLC). Following a trauma, the patient
      developed a bruise on the left inch. Because the site of shock seemed clinically
      infected, oral amoxicilline-acid clavulanic (AAC) treatment was started after
      withdrawn 1 set of blood cultures. These blood culture specimens yielded a Gram
      positive bacillus identified as E. rhusiopathiae by mass spectrometry MALDI-TOF
      (Microflex Bruker). The strain was sensitive to beta-lactam, fluoroquinolones and
      macrolides, resistant to vancomycin (natural resistance), and amikacin but
      sensitive to gentamicin. After 5 days of treatment by AAC, the patient became
      apyretic. One year after this episode, we reported no further symptoms of
      infection, or endocarditis. The natural resistance of E. rhusiopathiae in
      glycopeptides underlines the importance of a microbiological diagnosis. Indeed,
      vancomycine can be the treatment of first intention in Gram-positive bacillus
      bacteremia. The identification of bacteria using mass spectrometry is available
      the same day of the blood culture positivity and allows to prescribe the most
      adapted antibiotic treatment for the patient.

PMID- 27707677
TI  - Verification of a quantitative method: complete blood count by flow cytometry,
      the HematoFlowTM system (Beckman Coulter).
AB  - The HematoFlowTM system is used in the hematology laboratory of the University
      Hospital of Bordeaux since July, 2011. The HematoFlowTM solution is the
      combination of a sample preparator (FP1000) and a 5 color flow cytometer (FC500)
      linked by a middleware (RemisolTM). This system is used in second line when flags
      are activated by the hematology instrument and/or if the sample comes from the
      OncoHematology Department. Improvements in hematology disease diagnosis and
      follow-up were possible using this system. The laboratory has now entered in an
      accreditation procedure and needs to check this method in compliance with the
      COFRAC requirements.

PMID- 27707678
TI  - Cutaneous Mycobacterium massiliense infection after body piercing.

PMID- 27707679
TI  - Relapsed nasal extranodal NK/T-cell lymphoma with secondary cutaneous involvement
      presenting as a phlegmon-like lesion.

PMID- 27707680
TI  - Incidentally detected breast lesions on chest CT with US correlation: a pictorial
      essay.
AB  - With the increasing use of computed tomography (CT), incidental breast lesions
      are detected more frequently. When interpreting chest CT findings, it is
      important for radiologists to carefully review the breast to recognize any
      abnormal findings that could affect patient management. The purpose of this study
      is to discuss incidental breast lesions on chest CT with ultrasonography
      correlation that may be encountered in routine clinical practice.

PMID- 27707681
TI  - [Heart disease in sports horses: Current recommendations of the 2014 ACVIM /
      ECEIM consensus statement].
AB  - INTRODUCTION: Heart murmurs and arrhythmias are common in horses. Assessment of
      their clinical relevance concerning health, performance, safety and longevity of
      sports horses is of highest importance. A comprehensive cardiovascular
      examination is crucial for diagnosis and assessment of the severity of disease.
      Recently, an expert panel of the American College of Veterinary Internal Medicine
      (ACVIM) and the European College of Equine Internal Medicine (ECEIM) developed a
      consensus statement containing recommendations for sports horses with heart
      disease. This article summarizes the most relevant recommendations for
      practitioners, considering the most common and most important cardiac disorders
      in adult sports horses. These include mitral, aortic and tricuspid insufficiency,
      ventricular septal defects, atrial fibrillation as well as supraventricular and
      ventricular arrhythmias. Despite the fact that most horses with cardiovascular
      disease maintain a sufficient performance capacity, regular evaluations are
      indicated in horses with clinically relevant disorders. Under certain
      circumstances, horses with moderate to severe structural disease, with persistent
      untreated atrial fibrillation and with certain ventricular arrhythmias might
      still be used by informed adult riders. Horses with complex ventricular
      arrhythmias, pulmonary hypertension or congestive heart failure must not be
      ridden or driven and should be retired.

PMID- 27707682
TI  - Detection of 'Candidatus Neoehrlichia mikurensis' and other Anaplasmataceae and
      Rickettsiaceae in Canidae in Switzerland and Mediterranean countries.
AB  - INTRODUCTION: 'Candidatus Neoehrlichia mikurensis' is an emerging tick-borne
      zoonotic agent that primarily affects immunocompromised human patients. Dogs and
      foxes are frequently exposed to ticks, and both species are in close proximity to
      humans. This is the first study to systematically investigate the occurrence of
      'Candidatus Neoehrlichia mikurensis' in Canidae in Europa. We analyzed 1'739
      blood samples from dogs in Switzerland, Italy, Spain and Portugal and 162 blood
      samples from free-ranging red foxes (Vulpes vulpes) in Switzerland. All samples
      were tested using a previously described multiplex real-time PCR for the
      Anaplasmataceae family, the 'Candidatus Neoehrlichia' genus and the 'Candidatus
      Neoehrlichia mikurensis' species. All Anaplasmataceae positive samples were
      subsequently tested using specific real-time PCRs for Anaplasma phagocytophilum,
      Anaplasma platys, Ehrlichia canis and Rickettsia helvetica. Among the tested
      animals, one dog from Zurich tested positive for 'Candidatus Neoehrlichia
      mikurensis'. The 12-year old West Highland white terrier had been splenectomized
      3 months prior to the blood collection and presented with polyuria/polydipsia.
      Fanconi syndrome was diagnosed based on glucosuria with normoglycemia and
      hyperaminoaciduria. A. platys and E. canis were detected in 14/249 dogs from
      Sicily and Portugal; two of the dogs were coinfected with both agents. Four Swiss
      foxes tested positive for A. phagocytophilium. R. helvetica was detected for the
      first time in a red fox. In conclusion, 'Candidatus Neoehrlichia mikurensis'
      infection should be considered in sick dogs, particularly when immunocompromised.
      The pathogen seems not to be widespread in Canidae in the investigated countries.
      Conversely, other Anaplasmataceae were more readily detected in dogs and foxes.

PMID- 27707683
TI  - Unexplained bleeding as primary clinical complaint in dogs infected with
      Angiostrongylus vasorum.
AB  - INTRODUCTION: Unexplained bleeding was the primary clinical complaint in 15 dogs
      diagnosed with A. vasorum and was observed in the mouth, as external bleeding, as
      large subcutaneous hematoma, as hemoptysis, in the brain, post ovariectomy, as
      epistaxis, in the anterior ocular chamber and on a tracheal intubation tube. In 8
      dogs the cause of bleeding initially was suspected to be a minor trauma or a
      surgical complication, and various surgical approaches had been undertaken to
      eliminate the problem. In only 3 dogs respiratory signs were observed before the
      bleeding prompted referral. The median time elapsed between the first recognized
      clinical signs attributed to A. vasorum until diagnosis was 2 weeks (range1 day
      to 4 months). Four dogs died, 3 on the day of admission and 1 dog 4 days after
      admission. Suspected causes of death were respiratory failure and cerebral
      hemorrhage in 2 dogs each. Four dogs had been pre-treated with NSAIDs; of these,
      2 dogs developed severe hemoptysis (1 died), 1 dog developed brain hemorrhage
      (and died), and 1 dog developed a large subcutaneous hematoma with marked anemia.
      Bleeding at various sites may be the only recognized abnormality in A. vasorum
      infection. Without a high index of suspicion, the diagnosis and appropriate
      therapy may be delayed to the point of a fatal outcome. Tests of coagulation were
      quite variable and the cause of bleeding likely multifactorial.

PMID- 27707684
TI  - [Uroliths of cats in Switzerland from 2002 to 2009].
AB  - INTRODUCTION: In this study data on composition of uroliths collected from cats
      and epidemiologic data of affected cats in Switzerland from 2002 to 2009 are
      summarised. Of 884 stones analysed 50% (n=441) were composed of calcium oxalate,
      45% (n=398) of struvite, 3% (n=18) of ammonium urate, 1% (n=12) were mixed
      stones, 1% (n=9) were composed of silica, 3 stones were solidified blood, 2
      consisted of cystine and 1of xanthine. 40% of the ureteral stones were composed
      of struvite. Domestic cats had significantly less calcium oxalate stones compared
      to British Shorthair or Persian cats. Cats with calcium oxalate stones were older
      and cats with struvite stones were younger than other affected cats. Female and
      male cats were equally affected with stones. Compared to studies from other
      countries, in Switzerland silica stones occurred more often and ureteral stones
      were more often composed of Struvite. The present study shows that occurrence and
      prevalence of urinary calculi of cats from Switzerland exhibited only slight
      differences to studies from other countries.

PMID- 27707685
TI  - Using Knowledge Translation to Craft "Sticky" Social Media Health Messages That
      Provoke Interest, Raise Awareness, Impart Knowledge, and Inspire Change.
AB  - BACKGROUND: In Australia, there is growing use of technology supported knowledge
      translation (KT) strategies such as social media and mobile apps in health
      promotion and in Indigenous health. However, little is known about how
      individuals use technologies and the evidence base for the impact of these health
      interventions on health behavior change is meager. OBJECTIVE: The objective of
      our study was to examine how Facebook is used to promote health messages to
      Indigenous people and discuss how KT can support planning and implementing health
      messages to ensure chosen strategies are fit for the purpose and achieve impact.
      METHODS: A desktop audit of health promotion campaigns on smoking prevention and
      cessation for Australian Indigenous people using Facebook was conducted. RESULTS:
      Our audit identified 13 out of 21 eligible campaigns that used Facebook. Facebook
      pages with the highest number of likes (more than 5000) were linked to a website
      and to other social media applications and demonstrated stickiness
      characteristics by posting frequently (triggers and unexpected), recruiting
      sporting or public personalities to promote campaigns (social currency and
      public), recruiting Indigenous people from the local region (stories and
      emotion), and sharing stories and experiences based on real-life events (credible
      and practical value). CONCLUSIONS: KT planning may support campaigns to identify
      and select KT strategies that are best suited and well-aligned to the campaign's
      goals, messages, and target audiences. KT planning can also help mitigate
      unforeseen and expected risks, reduce unwarranted costs and expenses, achieve
      goals, and limit the peer pressure of using strategies that may not be fit for
      purpose. One of the main challenges in using KT systems and processes involves
      coming to an adequate conceptualization of the KT process itself.

PMID- 27707687
TI  - A Checklist for the Conduct, Reporting, and Appraisal of Microcosting Studies in
      Health Care: Protocol Development.
AB  - BACKGROUND: Microcosting is a cost estimation method that requires the collection
      of detailed data on resources utilized, and the unit costs of those resources in
      order to identify actual resource use and economic costs. Microcosting findings
      reflect the true costs to health care systems and to society, and are able to
      provide transparent and consistent estimates. Many economic evaluations in health
      and medicine use charges, prices, or payments as a proxy for cost. However, using
      charges, prices, or payments rather than the true costs of resources can result
      in inaccurate estimates. There is currently no existing checklist or guideline
      for the conduct, reporting, or appraisal of microcosting studies in health care
      interventions. OBJECTIVE: The aim of this study is to create a checklist and
      guideline for the conduct, reporting, and appraisal of microcosting studies in
      health care interventions. METHODS: Appropriate potential domains and items will
      be identified through (1) a systematic review of all published microcosting
      studies of health and medical interventions, strategies, and programs; (2) review
      of published checklists and guidelines for economic evaluations of health
      interventions, and selection of items relevant for microcosting studies; and (3)
      theoretical analysis of economic concepts relevant for microcosting. Item
      selection, formulation, and reduction will be conducted by the research team in
      order to develop an initial pool of items for evaluation by an expert panel
      comprising individuals with expertise in microcosting and economic evaluation of
      health interventions. A modified Delphi process will be conducted to achieve
      consensus on the checklist. A pilot test will be conducted on a selection of the
      articles selected for the previous systematic review of published microcosting
      studies. RESULTS: The project is currently in progress. CONCLUSIONS:
      Standardization of the methods used to conduct, report or appraise microcosting
      studies will enhance the consistency, transparency, and comparability of future
      microcosting studies. This will be the first checklist for microcosting studies
      to accomplish these goals and will be a timely and important contribution to the
      health economic and health policy literature. In addition to its usefulness to
      health economists and researchers, it will also benefit journal editors and
      decision-makers who require accurate cost estimates to deliver health care.

PMID- 27707686
TI  - Effects of the Web Behavior Change Program for Activity and Multimodal Pain
      Rehabilitation: Randomized Controlled Trial.
AB  - BACKGROUND: Web-based interventions with a focus on behavior change have been
      used for pain management, but studies of Web-based interventions integrated in
      clinical practice are lacking. To emphasize the development of cognitive skills
      and behavior, and to increase activity and self-care in rehabilitation, the Web
      Behavior Change Program for Activity (Web-BCPA) was developed and added to
      multimodal pain rehabilitation (MMR). OBJECTIVE: The objective of our study was
      to evaluate the effects of MMR in combination with the Web-BCPA compared with MMR
      among persons with persistent musculoskeletal pain in primary health care on pain
      intensity, self-efficacy, and copying, as part of a larger collection of data.
      Web-BCPA adherence and feasibility, as well as treatment satisfaction, were also
      investigated. METHODS: A total of 109 participants, mean age 43 (SD 11) years,
      with persistent pain in the back, neck, shoulder, and/or generalized pain were
      recruited to a randomized controlled trial with two intervention arms: (1)
      MMR+WEB (n=60) and (2) MMR (n=49). Participants in the MMR+WEB group self-guided
      through the eight modules of the Web-BCPA: pain, activity, behavior, stress and
      thoughts, sleep and negative thoughts, communication and self-esteem, solutions,
      and maintenance and progress. Data were collected with a questionnaire at
      baseline and at 4 and 12 months. Outcome measures were pain intensity (Visual
      Analog Scale), self-efficacy to control pain and to control other symptoms
      (Arthritis Self-Efficacy Scale), general self-efficacy (General Self-Efficacy
      Scale), and coping (two-item Coping Strategies Questionnaire; CSQ). Web-BCPA
      adherence was measured as minutes spent in the program. Satisfaction and Web-BCPA
      feasibility were assessed by a set of items. RESULTS: Of 109 participants, 99
      received the allocated intervention (MMR+WEB: n=55; MMR: n=44); 88 of 99 (82%)
      completed the baseline and follow-up questionnaires. Intention-to-treat analyses
      were performed with a sample size of 99. The MMR+WEB intervention was effective
      over time (time*group) compared to MMR for the two-item CSQ catastrophizing
      subscale (P=.003), with an effect size of 0.61 (Cohen d) at 12 months. There were
      no significant between-group differences over time (time*group) regarding pain
      intensity, self-efficacy (pain, other symptoms, and general), or regarding six
      subscales of the two-item CSQ. Improvements over time (time) for the whole study
      group were found regarding mean (P<.001) and maximum (P=.002) pain intensity. The
      mean time spent in the Web-based program was 304 minutes (range 0-1142).
      Participants rated the items of Web-BCPA feasibility between 68/100 and 90/100.
      Participants in the MMR+WEB group were more satisfied with their MMR at 4 months
      (P<.001) and at 12 months (P=.003). CONCLUSIONS: Adding a self-guided Web-based
      intervention with a focus on behavioral change for activity to MMR can reduce
      catastrophizing and increase satisfaction with MMR. Patients in MMR may need more
      supportive coaching to increase adherence in the Web-BCPA to find it valuable.
      CLINICALTRIAL: Clinicaltrials.gov NCT01475591;
      https://clinicaltrials.gov/ct2/show/NCT01475591 (Archived by WebCite at
      http://www.webcitation.org/6kUnt7VQh).

PMID- 27707688
TI  - A Randomized Controlled Trial Protocol to Evaluate the Effectiveness of an
      Integrated Care Management Approach to Improve Adherence Among HIV-Infected
      Patients in Routine Clinical Care: Rationale and Design.
AB  - BACKGROUND: Adherence to antiretroviral medications is a key determinant of
      clinical outcomes. Many adherence intervention trials investigated the effects of
      time-intensive or costly interventions that are not feasible in most clinical
      care settings. OBJECTIVE: We set out to evaluate a collaborative care approach as
      a feasible intervention applicable to patients in clinical care including those
      with mental illness and/or substance use issues. METHODS: We developed a
      randomized controlled trial (RCT) investigating an integrated, clinic-based care
      management approach to improve clinical outcomes that could be integrated into
      the clinical care setting. This is based on the routine integration and
      systematic follow-up of a clinical assessment of patient-reported outcomes
      targeting adherence, depression, and substance use, and adapts previously
      developed and tested care management approaches. The primary health coach or care
      management role is provided by clinic case managers allowing the intervention to
      be generalized to other human immunodeficiency virus (HIV) clinics that have case
      managers. We used a stepped-care approach to target interventions to those at
      greatest need who are most likely to benefit rather than to everyone to maintain
      feasibility in a busy clinical care setting. RESULTS: The National Institutes of
      Health funded this study and had no role in study design, data collection, or
      decisions regarding whether or not to submit manuscripts for publication. This
      trial is currently underway, enrollment was completed in 2015, and follow-up time
      still accruing. First results are expected to be ready for publication in early
      2017. DISCUSSION: This paper describes the protocol for an ongoing clinical trial
      including the design and the rationale for key methodological decisions. There is
      a need to identify best practices for implementing evidence-based collaborative
      care models that are effective and feasible in clinical care. Adherence efficacy
      trials have not led to sufficient improvements, and there remains little guidance
      regarding how adherence interventions should be implemented into clinical care.
      By focusing on improving adherence within care settings using existing staff,
      routine assessment of key domains, such as depression, adherence, and substance
      use, and feasible interventions, we propose to evaluate this innovative way to
      improve clinical outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01505660;
      http://clinicaltrials.gov/ct2/show/NCT01505660 (Archived by WebCite at
      http://www.webcitation/ 6ktOq6Xj7).

PMID- 27707690
TI  - Making isotonic milk. Focus on "Ca2+-activated Cl- channel currents in mammary
      secretory cells from lactating mouse".

PMID- 27707691
TI  - Optical coherence tomography angiography: an overview of the technology and an
      assessment of applications for clinical research.
AB  - In recent years, ophthalmology has experienced significant developments with
      respect to imaging modalities. Optical coherence tomography angiography is one
      such technology that seeks to improve diagnostics for retinal diseases. Using
      standard structural ocular coherence tomography hardware, optical coherence
      tomography angiography demonstrates the ability to non-invasively visualise the
      vasculature in the retina and the choroid with high resolution, allowing greater
      insight into retinal vascular pathologies. In addition, retinal and choroidal
      vessel density and blood flow can be quantified, offering potential to assist in
      the diagnosis of a variety of retinal diseases. To date, numerous retinal
      diseases, such as open-angle glaucoma, have been found to possess a vascular
      component. Specifically, ischaemia of the optic nerve head and lamina cribrosa
      has been theorised as a causative factor in ganglion cell death; however,
      confirmation of this mechanism has been prohibited by the limitations of
      currently existing imaging modalities. Optical coherence tomography angiography
      provides clear imaging of these regions and the possibility to elucidate further
      understanding of vascular factors that contribute to glaucoma development and
      progression. Furthermore, this imaging modality may provide insight to neural
      pathologies with vascular components such as Alzheimer's disease. Herein, the
      authors discuss the theory of operation for optical coherence tomography
      angiography and the current findings from pilot studies with a focus on open
      angle glaucoma. In addition, speculation is offered for future applications of
      the technology to study other diseases with microvascular contributions.

PMID- 27707689
TI  - Caveolin-3 plays a critical role in autophagy after ischemia-reperfusion.
AB  - Autophagy is a dynamic recycling process responsible for the breakdown of
      misfolded proteins and damaged organelles, providing nutrients and energy for
      cellular renovation and homeostasis. Loss of autophagy is associated with
      cardiovascular diseases. Caveolin-3 (Cav-3), a muscle-specific isoform, is a
      structural protein within caveolae and is critical to stress adaptation in the
      heart. Whether Cav-3 plays a role in regulating autophagy to modulate cardiac
      stress responses remains unknown. In the present study, we used HL-1 cells, a
      cardiac muscle cell line, with stable Cav-3 knockdown (Cav-3 KD) and Cav-3
      overexpression (Cav-3 OE) to study the impact of Cav-3 in regulation of
      autophagy. We show that traditional stimulators of autophagy (i.e., rapamycin and
      starvation) result in upregulation of the process in Cav-3 OE cells while Cav-3
      KD cells have a blunted response. Cav-3 coimmunoprecipitated with beclin-1 and
      Atg12, showing an interaction of caveolin with autophagy-related proteins. In the
      heart, autophagy may be a major regulator of protection from ischemic stress. We
      found that Cav-3 KD cells have a decreased expression of autophagy markers
      [beclin-1, light chain (LC3-II)] after simulated ischemia and ischemia
      reperfusion (I/R) compared with WT, whereas OE cells showed increased expression.
      Moreover, Cav-3 KD cells showed increased cell death and higher level of
      apoptotic proteins (cleaved caspase-3 and cytochrome c) with suppressed
      mitochondrial function in response to simulated ischemia and I/R, whereas Cav-3
      OE cells were protected and had preserved mitochondrial function. Taken together,
      these results indicate that autophagy regulates adaptation to cardiac stress in a
      Cav-3-dependent manner.

PMID- 27707692
TI  - Changes in subfoveal choroidal thickness and reduction of serum levels of
      vascular endothelial growth factor in patients with POEMS syndrome.
AB  - AIMS: To determine the changes in the subfoveal choroidal thickness (CT), the
      foveal thickness (FT) and the serum level of vascular endothelial growth factor
      (VEGF) after thalidomide treatment in patients with polyneuropathy, organomegaly,
      endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. METHODS:
      We studied 13 left eyes of 13 treatment-naive patients with POEMS syndrome. The
      subfoveal CT and FT were determined by enhanced depth imaging optical coherence
      tomography, and the serum level of VEGF was determined by ELISA at the baseline
      and at 6 months after thalidomide treatment. The correlations in the serum level
      of VEGF and the subfoveal CT or the FT at the baseline and at 6 months after
      treatment were determined. RESULTS: Together with the reduction in the serum
      level of VEGF, the subfoveal CT was also reduced significantly from 439.1+/-66.5
      um at the baseline to 307.2+/-75.4 um at 6 months (p=0.001). The mean FT at the
      baseline was 236.4+/-30.7 um which did not change significantly at 6 months at
      228.1+/-33.1 um (p>0.05). The change in the subfoveal CT was significantly and
      linearly correlated with the change in the serum level of VEGF at 6 months after
      treatment (r=0.67, p=0.011). CONCLUSIONS: The significant correlation between the
      CT and the serum level of VEGF may offer clues on the pathogenesis of ocular
      diseases of POEMS syndrome and on the role of serum VEGF on the choroid.

PMID- 27707693
TI  - What a patient with a learning disability would like you to know.

PMID- 27707694
TI  - Infantile wheeze: rethinking dogma.
AB  - Wheeze is a common symptom in young children and is usually associated with viral
      illnesses. It is a major source of morbidity and is responsible for a high
      consumption of healthcare and economic resources worldwide. A few children have a
      condition resembling classical asthma. Rarer specific conditions may have a
      wheezy component and should be considered in the differential diagnosis. Over the
      last half century, there have been many circular discussions about the best way
      of managing preschool wheeze. In general, intermittent wheezing should be treated
      with intermittent bronchodilator therapy, and a controller therapy should be
      prescribed for a young child with recurrent wheezing only if positively
      indicated, and only then if carefully monitored for efficacy. Good
      multidisciplinary support, attention to environmental exposition and education
      are essential in managing this common condition. This article analyses the
      pathophysiological basis of wheezing in infancy and critically discusses the
      evolution of the scientific progress over time in this unique field of
      respiratory medicine.

PMID- 27707697
TI  - NICE recommends first drug through "managed access" model of the Cancer Drugs
      Fund.

PMID- 27707695
TI  - Sugar and Type 2 diabetes.
AB  - BACKGROUND: Consumption of sugar, specifically sugar-sweetened beverages, has
      been widely held responsible by the media for the global rise in Type 2 diabetes
      (T2DM). SOURCES OF DATA: Systematic reviews and dietary guidelines relating
      dietary sugars to T2DM. AREAS OF AGREEMENT: Weight gain and T2DM incidence are
      associated with diet and lifestyle patterns characterized by high consumptions of
      any sweetened beverages. High sugar intakes impair risk factors for macrovascular
      complications of T2DM. AREAS OF CONTROVERSY: Much of the association between
      sugars and T2DM is eliminated by adjusting data for body mass index (BMI).
      However, BMI adjustment does not fully account for adiposity (r2=0.65-0.75).
      Excess sugar can promote weight gain, thus T2DM, through extra calories, but has
      no unique diabetogenic effect at physiological levels. GROWING POINTS: Ethical
      concerns about caffeine added to sweetened beverages, undetectable by consumers,
      to increase consumption. AREAS TIMELY FOR DEVELOPING RESEARCH: Evidence needed
      for limiting dietary sugar below 10% energy intake.

PMID- 27707698
TI  - Should all GPs become NHS employees?

PMID- 27707699
TI  - Effect of transcutaneous electrical acupuncture point stimulation at different
      frequencies in a rat model of neuropathic pain.
AB  - BACKGROUND: Acupuncture and related techniques are used worldwide to alleviate
      pain; however, their mechanisms of action are still not fully understood. In the
      present study, we investigated the effect of transcutaneous electrical
      acupuncture point stimulation (TEAS) at different frequencies in a chronic
      constriction injury (CCI) model of neuropathic pain in rats. METHODS: CCI was
      induced by ligating the common sciatic nerve, which produced neuropathic pain. 18
      male Sprague-Dawley rats with CCI were randomly divided into three groups (n=6
      each) that remained untreated (CCI group) or received TEAS at high frequency
      (CCI+TEAS-H group) or TEAS at low frequency (CCI+TEAS-L group). Rats in the
      CCI+TEAS-H group received high frequency stimulation (6-9 mA, 100 Hz) at
      GB34/GV26/ST36; those in the CCI+TEAS-L group received low frequency stimulation
      (6-9 mA, 2 Hz) at the same points. Rats in the control group had the same
      electrodes applied but received no stimulation. All three groups were subjected
      to behavioural studies after treatment. Expression of MU opioid receptors (MORs)
      in the L3-L5 dorsal root ganglion (DRG) was determined by immunofluorescence
      staining and Western blotting after treatment. RESULTS: Compared with the
      untreated CCI group, both mechanical allodynia and thermal hypergesia were
      significantly attenuated, and MOR expression in the DRG was significantly
      increased by low frequency TEAS treatment at GB34/GV26/ST36 (p<0.05). In
      contrast, no significant differences were observed between the CCI and CCI+TEAS-H
      groups. CONCLUSIONS: The use of low frequency TEAS significantly mitigated
      neuropathic pain in this rat model, and its analgesic effect is likely mediated
      by upregulation of MOR expression in the DRG.

PMID- 27707700
TI  - Cognitive, Linguistic, and Motor Abilities in a Multigenerational Family with
      Childhood Apraxia of Speech.
AB  - OBJECTIVE: This study describes the phenotype in a large family with a strong,
      multigenerational history of severe speech sound disorder (SSD) persisting into
      adolescence and adulthood in approximately half the cases. Aims were to determine
      whether a core phenotype, broader than speech, separated persistent from resolved
      SSD cases; and to ascertain the uniqueness of the phenotype relative to published
      cases. METHOD: Eleven members of the PM family (9-55 years) were assessed across
      cognitive, language, literacy, speech, phonological processing, numeracy, and
      motor domains. Between group comparisons were made using the Mann-Whitney U-test
      (p < 0.01). Participant performances were compared to normative data using
      standardized tests and to the limited published data on persistent SSD
      phenotypes. RESULTS: Significant group differences were evident on multiple
      speech, language, literacy, phonological processing, and verbal intellect
      measures without any overlapping scores. Persistent cases performed within the
      impaired range on multiple measures. Phonological memory impairment and subtle
      literacy weakness were present in resolved SSD cases. CONCLUSION: A core
      phenotype distinguished persistent from resolved SSD cases that was characterized
      by a multiple verbal trait disorder, including Childhood Apraxia of Speech.
      Several phenotypic differences differentiated the persistent SSD phenotype in the
      PM family from the few previously reported studies of large families with SSD,
      including the absence of comorbid dysarthria and marked orofacial apraxia. This
      study highlights how comprehensive phenotyping can advance the behavioral study
      of disorders, in addition to forming a solid basis for future genetic and neural
      studies.

PMID- 27707701
TI  - Moderate folic acid supplementation and MTHFD1-synthetase deficiency in mice, a
      model for the R653Q variant, result in embryonic defects and abnormal placental
      development.
AB  - BACKGROUND: Moderately high folic acid intake in pregnant women has led to
      concerns about deleterious effects on the mother and fetus. Common polymorphisms
      in folate genes, such as methylenetetrahydrofolate dehydrogenase
      methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase
      (MTHFD1) R653Q, may modulate the effects of elevated folic acid intake.
      OBJECTIVES: We investigated the effects of moderate folic acid supplementation on
      reproductive outcomes and assessed the potential interaction of the supplemented
      diet with MTHFD1-synthetase (Mthfd1S) deficiency in mice, which is a model for
      the R653Q variant. DESIGN: Female Mthfd1S+/+ and Mthfd1S+/- mice were fed a folic
      acid-supplemented diet (FASD) (5-fold higher than recommended) or control diets
      before mating and during pregnancy. Embryos and placentas were assessed for
      developmental defects at embryonic day 10.5 (E10.5). Maternal folate and choline
      metabolites and gene expression in folate-related pathways were examined.
      RESULTS: The combination of FASD and maternal MTHFD1-synthetase deficiency led to
      a greater incidence of defects in E10.5 embryos (diet * maternal genotype, P =
      0.0016; diet * embryonic genotype, P = 0.054). The methylenetetrahydrofolate
      reductase (MTHFR) protein and methylation potential [ratio of S
      adenosylmethionine (major methyl donor):S-adenosylhomocysteine) were reduced in
      maternal liver. Although 5-methyltetrahydrofolate (methylTHF) was higher in
      maternal circulation, the methylation potential was lower in embryos. The
      presence of developmental delays and defects in Mthfd1S+/- embryos was associated
      with placental defects (P = 0.003). The labyrinth layer failed to form properly
      in the majority of abnormal placentas, which compromised the integration of the
      maternal and fetal circulation and presumably the transfer of methylTHF and other
      nutrients. CONCLUSIONS: Moderately higher folate intake and MTHFD1-synthetase
      deficiency in pregnant mice result in a lower methylation potential in maternal
      liver and embryos and a greater incidence of defects in embryos. Although
      maternal circulating methylTHF was higher, it may not have reached the embryos
      because of abnormal placental development; abnormal placentas were observed
      predominantly in abnormally developed embryos. These findings have implications
      for women with high folate intakes, particularly if they are polymorphic for
      MTHFD1 R653Q.

PMID- 27707702
TI  - Accelerometer-measured dose-response for physical activity, sedentary time, and
      mortality in US adults.
AB  - BACKGROUND: Moderate-to-vigorous-intensity physical activity is recommended to
      maintain and improve health, but the mortality benefits of light activity and
      risk for sedentary time remain uncertain. OBJECTIVES: Using accelerometer-based
      measures, we 1) described the mortality dose-response for sedentary time and
      light- and moderate-to-vigorous-intensity activity using restricted cubic
      splines, and 2) estimated the mortality benefits associated with replacing
      sedentary time with physical activity, accounting for total activity. DESIGN: US
      adults (n = 4840) from NHANES (2003-2006) wore an accelerometer for <=7 d and
      were followed prospectively for mortality. Proportional hazards models were used
      to estimate adjusted HRs and 95% CIs for mortality associations with time spent
      sedentary and in light- and moderate-to-vigorous-intensity physical activity.
      Splines were used to graphically present behavior-mortality relation. Isotemporal
      models estimated replacement associations for sedentary time, and separate models
      were fit for low- (<5.8 h total activity/d) and high-active participants to
      account for nonlinear associations. RESULTS: Over a mean of 6.6 y, 700 deaths
      occurred. Compared with less-sedentary adults (6 sedentary h/d), those who spent
      10 sedentary h/d had 29% greater risk (HR: 1.29; 95% CI: 1.1, 1.5). Compared with
      those who did less light activity (3 h/d), those who did 5 h of light activity/d
      had 23% lower risk (HR: 0.77; 95% CI: 0.6, 1.0). There was no association with
      mortality for sedentary time or light or moderate-to-vigorous activity in highly
      active adults. In less-active adults, replacing 1 h of sedentary time with either
      light- or moderate-to-vigorous-intensity activity was associated with 18% and 42%
      lower mortality, respectively. CONCLUSIONS: Health promotion efforts for physical
      activity have mostly focused on moderate-to-vigorous activity. However, our
      findings derived from accelerometer-based measurements suggest that increasing
      light-intensity activity and reducing sedentary time are also important,
      particularly for inactive adults.

PMID- 27707704
TI  - Nephron morphometry in mice and rats using tomographic microscopy.
AB  - The aim was to quantify the glomerular capillary surface area, the segmental
      tubular radius, length, and area of single nephrons in mouse and rat kidneys.
      Multiple 2.5-um-thick serial Epon sections were obtained from three mouse and
      three rat kidneys for three-dimensional reconstruction of the nephron tubules.
      Micrographs were aligned for each kidney, and 359 nephrons were traced and their
      segments localized. Thirty mouse and thirty rat nephrons were selected for
      further investigation. The luminal radius of each segment was determined by two
      methods. The luminal surface area was estimated from the radius and length of
      each segment. High-resolution micrographs were recorded for five rat glomeruli,
      and the capillary surface area determined. The capillary volume and surface area
      were corrected for glomerular shrinkage. A positive correlation was found between
      glomerular capillary area and proximal tubule area. The thickest part of the
      nephron, i.e., the proximal tubule, was followed by the thinnest part of the
      nephron, i.e., the descending thin limb, and the diameters of the seven
      identified nephron segments share the same rank in the two species. The radius
      and length measurements from mouse and rat nephrons generally share the same
      pattern; rat tubular radius-to-mouse tubular radius ratio ~ 1.47, and rat tubular
      length-to-mouse tubular length ratio ~ 2.29, suggesting relatively longer tubules
      in the rat. The detailed tables of mouse and rat glomerular capillary area and
      segmental radius, length, and area values may be used to enhance understanding of
      the associated physiology, including existing steady-state models of the urine
      concentrating mechanism.

PMID- 27707703
TI  - The enigma of continual plasma volume expansion in pregnancy: critical role of
      the renin-angiotensin-aldosterone system.
AB  - Pregnancy is characterized by avid renal sodium retention and plasma volume
      expansion in the presence of decreased blood pressure. Decreased maternal blood
      pressure is a consequence of reduced systemic vascular tone, which results from
      an increased production of vasodilators [nitric oxide (NO), prostaglandins, and
      relaxin] and decreased vascular responsiveness to the potent vasoconstrictor
      (angiotensin II). The kidneys participate in this vasodilatory response,
      resulting in marked increases in renal plasma flow and glomerular filtration rate
      (GFR) during pregnancy. In women, sodium retention drives plasma volume expansion
      (~40%) and is necessary for perfusion of the growing uterus and fetus. For there
      to be avid sodium retention in the presence of the potent natriuretic influences
      of increased NO and elevated GFR, there must be modifications of the tubules to
      prevent salt wasting. The purpose of this review is to summarize these
      adaptations.

PMID- 27707705
TI  - A computational model for simulating solute transport and oxygen consumption
      along the nephrons.
AB  - The goal of this study was to investigate water and solute transport, with a
      focus on sodium transport (TNa) and metabolism along individual nephron segments
      under differing physiological and pathophysiological conditions. To accomplish
      this goal, we developed a computational model of solute transport and oxygen
      consumption (QO2 ) along different nephron populations of a rat kidney. The model
      represents detailed epithelial and paracellular transport processes along both
      the superficial and juxtamedullary nephrons, with the loop of Henle of each model
      nephron extending to differing depths of the inner medulla. We used the model to
      assess how changes in TNa may alter QO2 in different nephron segments and how
      shifting the TNa sites alters overall kidney QO2 Under baseline conditions, the
      model predicted a whole kidney TNa/QO2 , which denotes the number of moles of Na+
      reabsorbed per moles of O2 consumed, of ~15, with TNa efficiency predicted to be
      significantly greater in cortical nephron segments than in medullary segments.
      The TNa/QO2 ratio was generally similar among the superficial and juxtamedullary
      nephron segments, except for the proximal tubule, where TNa/QO2 was ~20% higher
      in superficial nephrons, due to the larger luminal flow along the juxtamedullary
      proximal tubules and the resulting higher, flow-induced transcellular transport.
      Moreover, the model predicted that an increase in single-nephron glomerular
      filtration rate does not significantly affect TNa/QO2 in the proximal tubules but
      generally increases TNa/QO2 along downstream segments. The latter result can be
      attributed to the generally higher luminal [Na+], which raises paracellular TNa
      Consequently, vulnerable medullary segments, such as the S3 segment and medullary
      thick ascending limb, may be relatively protected from flow-induced increases in
      QO2 under pathophysiological conditions.

PMID- 27707707
TI  - Insulin resistance in chronic kidney disease: a systematic review.
AB  - Insulin resistance (IR) is an early metabolic alteration in chronic kidney
      disease (CKD) patients, being apparent when the glomerular filtration rate is
      still within the normal range and becoming almost universal in those who reach
      the end stage of kidney failure. The skeletal muscle represents the primary site
      of IR in CKD, and alterations at sites beyond the insulin receptor are recognized
      as the main defect underlying IR in this condition. Estimates of IR based on
      fasting insulin concentration are easier and faster but may not be adequate in
      patients with CKD because renal insufficiency reduces insulin catabolism. The
      hyperinsulinemic euglycemic clamp is the gold standard for the assessment of
      insulin sensitivity because this technique allows a direct measure of skeletal
      muscle sensitivity to insulin. The etiology of IR in CKD is multifactorial in
      nature and may be secondary to disturbances that are prominent in renal diseases,
      including physical inactivity, chronic inflammation, oxidative stress, vitamin D
      deficiency, metabolic acidosis, anemia, adipokine derangement, and altered gut
      microbiome. IR contributes to the progression of renal disease by worsening renal
      hemodynamics by various mechanisms, including activation of the sympathetic
      nervous system, sodium retention, and downregulation of the natriuretic peptide
      system. IR has been solidly associated with intermediate mechanisms leading to
      cardiovascular (CV) disease in CKD including left ventricular hypertrophy,
      vascular dysfunction, and atherosclerosis. However, it remains unclear whether IR
      is an independent predictor of mortality and CV complications in CKD. Because IR
      is a modifiable risk factor and its reduction may lower CV morbidity and
      mortality, unveiling the molecular mechanisms responsible for the pathogenesis of
      CKD-related insulin resistance is of importance for the identification of novel
      therapeutic targets aimed at reducing the high CV risk of this condition.

PMID- 27707709
TI  - The end of Down's syndrome?

PMID- 27707710
TI  - Author's reply to Beekmann.

PMID- 27707708
TI  - Collecting duct-specific knockout of nitric oxide synthase 3 impairs water
      excretion in a sex-dependent manner.
AB  - Nitric oxide (NO) inhibits collecting duct (CD) Na+ and water reabsorption. Mice
      with CD-specific knockout (KO) of NO synthase 1 (NOS1) have salt-sensitive
      hypertension. In contrast, the role of NOS3 in CD salt and water reabsorption is
      unknown. Mice with CD NOS3 KO were generated with loxP-flanked exons 9-12
      (encodes the calmodulin binding site) of the NOS3 gene and the aquaporin-2
      promoter-Cre transgene. There were no differences between control and CD NOS3 KO
      mice, irrespective of sex, in food intake, water intake, urine volume, urinary
      Na+ or K+ excretion, plasma renin concentration, blood pressure, or pulse during
      7 days of normal (0.3%), high (3.17%), or low (0.03%) Na+ intake. Blood pressure
      was similar between genotypes during DOCA-high salt. CD NOS3 KO did not alter
      urine volume or urine osmolality after water deprivation. In contrast, CD NOS3 KO
      male, but not female, mice had lower urine volume and higher urine osmolality
      over the course of 7 days of water loading compared with control mice. Male, but
      not female, CD NOS3 KO mice had reduced urinary nitrite+nitrate excretion
      compared with controls after 7 days of water loading. Urine AVP and AVP
      stimulated cAMP accumulation in isolated inner medullary CD were similar between
      genotypes. Western analysis did not reveal a significant effect of CD NOS3 KO on
      renal aquaporin expression. In summary, these data suggest that CD NOS3 may be
      involved in the diuretic response to a water load in a sex-specific manner; the
      mechanism of this effect remains to be determined.

PMID- 27707706
TI  - Solute transport and oxygen consumption along the nephrons: effects of Na+
      transport inhibitors.
AB  - Sodium and its associated anions are the major determinant of extracellular fluid
      volume, and the reabsorption of Na+ by the kidney plays a crucial role in long
      term blood pressure control. The goal of this study was to investigate the extent
      to which inhibitors of transepithelial Na+ transport (TNa) along the nephron
      alter urinary solute excretion and TNa efficiency and how those effects may vary
      along different nephron segments. To accomplish that goal, we used the
      multinephron model developed in the companion study (28). That model represents
      detailed transcellular and paracellular transport processes along the nephrons of
      a rat kidney. We simulated the inhibition of the Na+/H+ exchanger (NHE3), the
      bumetanide-sensitive Na+-K+-2Cl- transporter (NKCC2), the Na+-Cl- cotransporter
      (NCC), and the amiloride-sensitive Na+ channel (ENaC). Under baseline conditions,
      NHE3, NKCC2, NCC, and ENaC reabsorb 36, 22, 4, and 7%, respectively, of filtered
      Na+ The model predicted that inhibition of NHE3 substantially reduced proximal
      tubule TNa and oxygen consumption (QO2 ). Whole-kidney TNa efficiency, as
      reflected by the number of moles of Na+ reabsorbed per moles of O2 consumed
      (denoted by the ratio TNa/QO2 ), decreased by ~20% with 80% inhibition of NHE3.
      NKCC2 inhibition simulations predicted a substantial reduction in thick ascending
      limb TNa and QO2 ; however, the effect on whole-kidney TNa/QO2 was minor. Tubular
      K+ transport was also substantially impaired, resulting in elevated urinary K+
      excretion. The most notable effect of NCC inhibition was to increase the
      excretion of Na+, K+, and Cl-; its impact on whole-kidney TNa and its efficiency
      was minor. Inhibition of ENaC was predicted to have opposite effects on the
      excretion of Na+ (increased) and K+ (decreased) and to have only a minor impact
      on whole-kidney TNa and TNa/QO2 Overall, model predictions agree well with
      measured changes in Na+ and K+ excretion in response to diuretics and Na+
      transporter mutations.

PMID- 27707711
TI  - Embryo Mortality Around the Period of Maintenance of the Corpus Luteum Causes
      Alterations to the Ovarian Function of Lactating Dairy Cows.
AB  - Objectives were to identify cows with embryo mortality (EM) around the period of
      corpus luteum maintenance by interferon tau (IFNT) and to characterize ovarian
      function in cows that underwent EM. Lactating Holstein cows received artificial
      insemination (AI) (Day = 0) with semen or extender only. From Day 14 to 42
      transrectal ultrasonography was performed daily to monitor ovarian dynamics and
      uterine contents whereas blood was collected every 48 h to determine ISG15 and
      MX2 mRNA abundance in blood mononuclear cells (Day 14 to 22 only) and
      determination of hormone concentrations. Cows were classified in the following
      reproductive status groups: cyclic (inseminated with extender; n = 15), pregnant
      (embryo present on Day 42; n = 23), no embryo (n = 23), and EM (n = 14). EM was
      defined as the presence of an embryo based on interferon-stimulated genes (ISG)
      mRNA abundance and concentrations of pregnancy-specific protein B (PSPB) above
      specific cutoff points but no embryo visualized by ultrasonography. Within the EM
      group, early EM (up to Day 22) was when ISG fold changes were above specific
      cutoff points from Day 18 to 22 and PSPB below 0.7 ng/ml on and after Day 24,
      whereas late EM (after Day 22) was when PSPB was above 0.7 ng/ml on or after Day
      24 regardless of ISG expression. This experiment provided evidence that the
      combination of ISG expression patterns and PSPB concentrations is a reasonable
      method to determine EM around the period of corpus luteum maintenance by IFNT
      because cows with evidence of EM had patterns of ISG expression more similar to
      pregnant than cyclic cows or cows with no embryo. Within the EM group, only cows
      with late EM had delayed luteal regression and longer interovulatory intervals.
      No major alterations in follicular function were observed after the onset of
      luteolysis. Our results suggest that embryo development needs to continue beyond
      22 days after AI to effectively prevent luteolysis and extend the luteal phase.

PMID- 27707712
TI  - Sperm-Coating Beta-Defensin 126 Is a Dissociation-Resistant Dimer Produced by
      Epididymal Epithelium in the Bovine Reproductive Tract.
AB  - Beta-defensins are innate immune molecules, often described as antimicrobial
      peptides because of their bactericidal activity and are now known to have diverse
      additional functions, including cell signaling, chemoattraction,
      immunoregulation, and reproduction. In humans and primates, beta-defensin 126 has
      been shown to regulate the ability of sperm to swim through cervical mucus and to
      protect sperm from attack by the female immune system during transit toward the
      oviduct. Bovine beta-defensin 126 (BBD126) is the ortholog of human defensin 126,
      and computational analysis here revealed significant conservation between BBD126
      and other mammalian orthologs at the N-terminus, although extensive sequence
      differences were detected at the C-terminus, implying possible species-specific
      roles for this beta-defensin in reproduction. We had previously demonstrated
      preferential expression of this and related beta-defensin genes in the bovine
      male reproductive tract, but no studies of bovine beta-defensin proteins have
      been performed to date. Here, we analyzed BBD126 protein using a monoclonal
      antibody (a-BBD126) generated against a 14 amino acid peptide sequence from the
      secreted fragment of BBD126. The specificity of a-BBD126 was validated by testing
      against the native form of the peptide recovered from bovine caudal epididymal
      fluid and recombinant BBD126 generated using a prokaryotic expression system.
      Western blot analysis of the native and recombinant forms showed that BBD126
      exists as a dimer that was highly resistant to standard methods of dissociation.
      Immunohistochemical staining using a-BBD126 demonstrated BBD126 protein
      expression by epithelial cells of the caudal epididymis and vas deferens from
      both mature and immature bulls. BBD126 could also be seen (by confocal
      microscopy) to coat caudal sperm, with staining concentrated on the tail of the
      sperm cells. This study is the first to demonstrate beta-defensin 126 protein
      expression in the bovine reproductive tract and on bull sperm. Its dissociation
      resistant dimeric structure is likely to have important functional implications
      for the role of BBD126 in bovine reproduction.

PMID- 27707714
TI  - The problem with "abstinence is unnecessary".

PMID- 27707713
TI  - Cauda Epididymis-Specific Beta-Defensin 126 Promotes Sperm Motility but Not
      Fertilizing Ability in Cattle.
AB  - Bovine beta-defensin 126 (BBD126) exhibits preferential expression for the cauda
      epididymis of males, where it is absorbed onto the tail and postacrosomal region
      of the sperm. The aim of this study was to examine the role of BBD126 in bull
      sperm function. Fresh and frozen-thawed semen were incubated in the presence of
      different capacitating agents as well as with phosphatidylinositol-specific
      phospholipase C. These treatments, which have been successful in releasing beta
      defensin 126 from macaque sperm, proved to be ineffective in bull sperm. This
      finding suggests that the protein behaves in a different manner in the bovine.
      The lack of success in removing BBD126 led us to use corpus epididymis sperm, a
      model in which the protein is not present, to study its functional role. Corpus
      sperm were incubated with cauda epididymal fluid (CEF) in the absence or presence
      of BBD126 antibody or with recombinant BBD126 (rBBD126). Confocal microscopy
      revealed that rBBD126 binds to corpus sperm with the same pattern observed for
      BBD126 in cauda sperm, whereas an aberrant binding pattern is observed when sperm
      are subject to CEF incubation. Addition of CEF increased motility as well as the
      number of corpus sperm migrating through cervical mucus from estrus cows.
      However, it decreased the ability of sperm to fertilize in vitro matured oocytes.
      The presence of the antibody failed to abrogate these effects. Furthermore, when
      rBBD126 was added in the absence of other factors and proteins from the CEF, an
      increase in motility was also observed and no negative effects in fertility were
      seen. These results suggest that BBD126 plays a key role in the acquisition of
      sperm motility in the epididymis.

PMID- 27707715
TI  - Mental illness is not a state of mind.

PMID- 27707716
TI  - 80% of China's clinical trial data are fraudulent, investigation finds.

PMID- 27707717
TI  - CLOCK regulates mammary epithelial cell growth and differentiation.
AB  - Circadian clocks influence virtually all physiological processes, including
      lactation. Here, we investigate the role of the CLOCK gene in regulation of
      mammary epithelial cell growth and differentiation. Comparison of mammary
      morphology in late-pregnant wild-type and ClockDelta19 mice, showed that gland
      development was negatively impacted by genetic loss of a functional timing
      system. To understand whether these effects were due, in part, to loss of CLOCK
      function in the gland, the mouse mammary epithelial cell line, HC11, was
      transfected with short hairpin RNA that targeted Clock (shClock). Cells
      transfected with shClock expressed 70% less Clock mRNA than wild-type (WT) HC11
      cultures, which resulted in significantly depressed levels of CLOCK protein (P <
      0.05). HC11 lines carrying shClock had four-fold higher growth rates (P < 0.05),
      and the percentage of cells in G1 phase was significantly higher (90.1 +/- 1.1%
      of shClock vs. 71.3 +/- 3.6% of WT-HC11) following serum starvation. Quantitative
      PCR (qPCR) analysis showed shClock had significant effects (P < 0.0001) on
      relative expression levels of Ccnd1, Wee1, and Tp63 qPCR analysis of the effect
      of shClock on Fasn and Cdh1 expression in undifferentiated cultures and cultures
      treated 96 h with dexamethasone, insulin, and prolactin (differentiated) found
      levels were reduced by twofold and threefold, respectively (P < 0.05), in shClock
      line relative to WT cultures. Abundance of CDH1 and TP63 proteins were
      significantly reduced in cultures transfected with shClock These data support how
      CLOCK plays a role in regulation of epithelial cell growth and differentiation in
      the mammary gland.

PMID- 27707718
TI  - Developmental plasticity of mitochondrial function in American alligators,
      Alligator mississippiensis.
AB  - The effect of hypoxia on cellular metabolism is well documented in adult
      vertebrates, but information is entirely lacking for embryonic organisms. The
      effect of hypoxia on embryonic physiology is particularly interesting, as
      metabolic responses during development may have life-long consequences, due to
      developmental plasticity. To this end, we investigated the effects of chronic
      developmental hypoxia on cardiac mitochondrial function in embryonic and juvenile
      American alligators (Alligator mississippiensis). Alligator eggs were incubated
      in 21% or 10% oxygen from 20 to 90% of embryonic development. Embryos were either
      harvested at 90% development or allowed to hatch and then reared in 21% oxygen
      for 3 yr. Ventricular mitochondria were isolated from embryonic/juvenile
      alligator hearts. Mitochondrial respiration and enzymatic activities of electron
      transport chain complexes were measured with a microrespirometer and
      spectrophotometer, respectively. Developmental hypoxia induced growth restriction
      and increased relative heart mass, and this phenotype persisted into juvenile
      life. Embryonic mitochondrial function was not affected by developmental hypoxia,
      but at the juvenile life stage, animals from hypoxic incubations had lower levels
      of Leak respiration and higher respiratory control ratios, which is indicative of
      enhanced mitochondrial efficiency. Our results suggest developmental hypoxia can
      have life-long consequences for alligator morphology and metabolic function.
      Further investigations are necessary to reveal the adaptive significance of the
      enhanced mitochondrial efficiency in the hypoxic phenotype.

PMID- 27707719
TI  - P2X7 receptors in body temperature, locomotor activity, and brain mRNA and lncRNA
      responses to sleep deprivation.
AB  - The ionotropic purine type 2X7 receptor (P2X7R) is a nonspecific cation channel
      implicated in sleep regulation and brain cytokine release. Many endogenous
      rhythms covary with sleep, including locomotor activity and core body
      temperature. Furthermore, brain-hypothalamic cytokines and purines play a role in
      the regulation of these physiological parameters as well as sleep. We
      hypothesized that these parameters are also affected by the absence of the P2X7
      receptor. Herein, we determine spontaneous expression of body temperature and
      locomotor activity in wild-type (WT) and P2X7R knockout (KO) mice and how they
      are affected by sleep deprivation (SD). We also compare hypothalamic,
      hippocampal, and cortical cytokine- and purine-related receptor and enzyme mRNA
      expressions before and after SD in WT and P2X7RKO mice. Next, in a hypothesis
      generating survey of hypothalamic long noncoding (lnc) RNAs, we compare lncRNA
      expression levels between strains and after SD. During baseline conditions,
      P2X7RKO mice had attenuated temperature rhythms compared with WT mice, although
      locomotor activity patterns were similar in both strains. After 6 h of SD, body
      temperature and locomotion were enhanced to a greater extent in P2X7RKO mice than
      in WT mice during the initial 2-3 h after SD. Baseline mRNA levels of cortical
      TNF-alpha and P2X4R were higher in the KO mice than WT mice. In response to SD,
      the KO mice failed to increase hypothalamic adenosine deaminase and P2X4R mRNAs.
      Further, hypothalamic lncRNA expressions varied by strain, and with SD. Current
      data are consistent with a role for the P2X7R in thermoregulation and lncRNA
      involvement in purinergic signaling.

PMID- 27707721
TI  - Breathing while altricial: the ontogeny of ventilatory chemosensitivity in red
      winged blackbird (Agelaius phoeniceus) nestlings.
AB  - Altricial bird species, like red-winged blackbirds, hatch at an immature state of
      functional maturity with limited aerobic capacity and no endothermic capacity.
      Over the next 10-12 days in the nest, red-winged blackbirds develop increased
      metabolic capacity before fledging. Although ontogeny of respiration has been
      described in precocial birds, ontogeny of ventilatory chemosensitivity is unknown
      in altricial species. Here we examined developmental changes in chemosensitivity
      of tidal volume (Vt), breathing frequency (f), minute ventilation (Ve), and whole
      animal oxygen consumption (Vo2) from hatching to just before fledging in red
      winged blackbirds on days 1, 3, 5, 7, and 9 posthatching (dph) in response to
      hypercapnia (2 and 4% CO2) and hypoxia (15 and 10% O2). Under control conditions,
      there was a developmental increase in Ve with age due to increased Vt Hypercapnic
      and hypoxic chemosensitivities were present as early as 1 dph. In response to
      hypoxia, 1, 3, and 9 dph nestlings increased Ve at 10% O2, by increasing f with
      some change in Vt in younger animals. In contrast to early neonatal altricial
      mammals, the hypoxic response of nestling red-winged blackbirds was not biphasic.
      In response to hypercapnia, 3 dph nestlings increased Ve by increasing both f and
      Vt From 5 dph on, the hypercapnic increase in Ve was accounted for by increased
      Vt and not f. Chemosensitivity to O2 and CO2 matures early in nestling red-winged
      blackbirds, well before the ability to increase Vo2 in response to cooling, and
      thus does not represent a limitation to the development of endothermy.

PMID- 27707720
TI  - Imatinib attenuates cerebrovascular injury and phenotypic transformation after
      intracerebral hemorrhage in rats.
AB  - This study explored the hypothesis that intracerebral hemorrhage (ICH) promotes
      release of diffusible factors that can significantly influence the structure and
      function of cerebral arteries remote from the site of injury, through action on
      platelet-derived growth factor (PDGF) receptors. Four groups of adult male
      Sprague-Dawley rats were studied (n = 8 each): 1) sham; 2) sham + 60 mg/kg ip
      imatinib; 3) ICH (collagenase method); and 4) ICH + 60 mg/kg ip imatinib given 60
      min after injury. At 24 h after injury, sham artery passive diameters (+3 mM
      EGTA) averaged 244 +/- 7 um (at 60 mmHg). ICH significantly increased passive
      diameters up to 6.4% and decreased compliance up to 42.5%. For both pressure- and
      potassium-induced contractions, ICH decreased calcium mobilization up to 26.2%
      and increased myofilament calcium sensitivity up to 48.4%. ICH reduced confocal
      colocalization of smooth muscle alpha-actin (alphaActin) with nonmuscle myosin
      heavy chain (MHC) and increased its colocalization with smooth muscle MHC,
      suggesting that ICH promoted contractile differentiation. ICH also enhanced
      colocalization of myosin light chain kinase (MLCK) with both alphaActin and
      regulatory 20-kDa myosin light chain. All effects of ICH on passive diameter,
      compliance, contractility, and contractile protein colocalization were
      significantly reduced or absent in arteries from animals treated with imatinib.
      These findings support the hypothesis that ICH promotes release into the
      cerebrospinal fluid of vasoactive factors that can diffuse to and promote
      activation of cerebrovascular PDGF receptors, thereby altering the structure,
      contractile protein organization, contractility, and smooth muscle phenotype of
      cerebral arteries remote from the site of hemorrhage.

PMID- 27707722
TI  - Vagal afferent activation induces salivation and swallowing-like events in
      anesthetized rats.
AB  - The aim of this study was to clarify the effect of vagal afferent activation on
      salivation and swallowing-like events. Salivation is part of a reflex induced by
      stimulation of the oral area during feeding or chewing. Recently, we reported
      that nausea induced by gastroesophageal reflux (GER) activation produced
      salivation and swallowing in humans. Here, we investigated the ability of
      visceral sensation to enhance salivation and swallowing in rodents in order to
      inform the mechanism of GER-mediated stomatognathic activation. First, we
      administered LiCl to anesthetized male rats to induce nausea. LiCl significantly
      increased salivation and increased the activity of the vagal afferent nerve.
      Next, we simultaneously recorded salivation and swallowing using an electrode
      attached to the mylohyoid muscle during vagal afferent stimulation in a
      physiological range of frequencies. Vagal afferent stimulation significantly
      increased salivation and swallowing-like events in a frequency-dependent manner.
      A muscle relaxant, vecuronium bromide, diminished the swallowing-like response
      but did not affect salivation. These results indicate that visceral sensation
      induces salivation and swallowing-like events in anesthetized rodents through
      vagal afferent activation.

PMID- 27707725
TI  - Advances in Technology: Blood-sampling at depth. Focus on "Development of an
      animal-borne blood sample collection device and its deployment for the
      determination of cardiovascular and stress hormones in submerged phocid seals".

PMID- 27707723
TI  - Acute hot water immersion is protective against impaired vascular function
      following forearm ischemia-reperfusion in young healthy humans.
AB  - Ischemia-reperfusion (I/R) injury is a primary cause of poor outcomes following
      ischemic cardiovascular events. We tested whether acute hot water immersion
      protects against forearm vascular I/R. Ten (5 male, 5 female) young (23 +/- 2
      yr), healthy subjects participated in two trials in random order 7-21 days apart,
      involving: 1) 60 min of seated rest (control), or 2) 60 min of immersion in 40.5
      degrees C water (peak rectal temperature: 38.9 +/- 0.2 degrees C). I/R was
      achieved 70 min following each intervention by inflating an upper arm cuff to 250
      mmHg for 20 min followed by 20 min of reperfusion. Brachial artery flow-mediated
      dilation (FMD) and forearm postocclusive reactive hyperemia (RH) were measured as
      markers of macrovascular and microvascular function at three time points: 1)
      preintervention, 2) 60 min postintervention, and 3) post-I/R. Neither time
      control nor hot water immersion alone affected FMD (both, P > 0.99). I/R reduced
      FMD from 7.4 +/- 0.7 to 5.4 +/- 0.6% (P = 0.03), and this reduction was prevented
      following hot water immersion (7.0 +/- 0.7 to 7.7 +/- 1.0%; P > 0.99). I/R also
      impaired RH (peak vascular conductance: 2.6 +/- 0.5 to 2.0 +/- 0.4 ml.min-1.mmHg
      1, P = 0.003), resulting in a reduced shear stimulus (SRAUC.10-3: 22.5 +/- 2.4 to
      16.9 +/- 2.4, P = 0.04). The post-I/R reduction in peak RH was prevented by hot
      water immersion (2.5 +/- 0.4 to 2.3 +/- 0.4 ml.min-1.mmHg-1; P = 0.33). We
      observed a decline in brachial artery dilator function post-I/R, which may be
      (partly) related to damage incurred downstream in the microvasculature, as
      indicated by impaired RH and shear stimulus. Hot water immersion was protective
      against reductions in FMD and RH post-I/R, suggesting heat stress induces
      vascular changes consistent with reducing I/R injury following ischemic events.

PMID- 27707724
TI  - Hyperinsulinemic-normoglycemic clamp administered together with amino acids
      induces anabolism after cardiac surgery.
AB  - Cardiac surgery triggers an inflammatory stress response, leading to protein
      catabolism, a process that even high-dose insulin therapy alone cannot reverse.
      To determine whether hyperinsulinemic-normoglycemic clamp and perioperative amino
      acid (AA) supplementation improves whole body protein balance, 20 patients
      scheduled for elective coronary artery bypass grafting surgery were randomly
      assigned to have intra- and postoperative hyperinsulinemic-normoglycemic clamp,
      with or without intravenous AA supplementation. Primed continuous infusions of
      [6,6-2H2]glucose and l-[1-13C]leucine were used to quantify whole body protein
      and glucose metabolism before and after surgery. Adipose tissue and serum
      cytokines were also analyzed to measure their responsiveness to the anabolic
      effect of AA administration. During hyperinsulinemic-normoglycemic clamp, AA
      supplementation successfully stimulated whole body protein synthesis, resulting
      in a positive whole body protein balance after surgery (insulin: -13.6 +/- 4.5
      vs. insulin + AA: 2.1 +/- 5.4 MUmol.kg-1.h-1, P < 0.001). Endogenous glucose
      production was equally suppressed in both groups (insulin: 0.0 +/- 3.8 vs.
      insulin + AA 1.6 +/- 1.6 MUmol.kg-1.min-1, P = 0.230). AA supplementation led to
      significant changes in serum and tissue IL-6 (insulin: 246.6 +/- 111.2 vs.
      insulin + AA: 124.5 +/- 79.3 pg/ml, P = 0.011). In conclusion, hyperinsulinemic
      normoglycemic clamp technique, together with AA supplementation, can induce an
      anabolic state after open-heart surgery, as quantified by a positive whole body
      protein balance.

PMID- 27707726
TI  - Oxygen signaling: call for papers.
AB  - Not applicable.

PMID- 27707727
TI  - Which intervention reduces the risk of preterm birth in women with risk factors?

PMID- 27707728
TI  - Harness shared data in international Zika registry.

PMID- 27707729
TI  - Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS).
AB  - Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease
      entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1)
      secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ
      damage. The aim of the study was to develop and validate diagnostic criteria for
      CAPS. An innovative process was followed including interdisciplinary team
      building, item generation: review of CAPS registries, systematic literature
      review, expert surveys, consensus conferences for item refinement, item reduction
      and weighting using 1000Minds decision software. Resulting CAPS criteria were
      tested in large cohorts of CAPS cases and controls using correspondence analysis.
      Diagnostic models were explored using sensitivity analyses. The international
      team included 16 experts. Systematic literature and registry review identified 33
      CAPS-typical items; the consensus conferences reduced these to 14. 1000Minds
      exercises ranked variables based on importance for the diagnosis. Correspondence
      analysis determined variables consistently associated with the diagnosis of CAPS
      using 284 cases and 837 controls. Seven variables were significantly associated
      with CAPS (p<0.001). The best diagnosis model included: Raised inflammatory
      markers (C-reactive protein/serum amyloid A) plus >=two of six CAPS-typical
      symptoms: urticaria-like rash, cold-triggered episodes, sensorineural hearing
      loss, musculoskeletal symptoms, chronic aseptic meningitis and skeletal
      abnormalities. Sensitivity was 81%, specificity 94%. It performed well for all
      CAPS subtypes and regardless of NLRP3 mutation. The novel approach integrated
      traditional methods of evidence synthesis with expert consensus, web-based
      decision tools and innovative statistical methods and may serve as model for
      other rare diseases. These criteria will enable a rapid diagnosis for children
      and adults with CAPS.

PMID- 27707731
TI  - Remission in SLE: the duration depends on multiple factors, including the
      definition.

PMID- 27707730
TI  - Discordance between tender and swollen joint count as well as patient's and
      evaluator's global assessment may reduce likelihood of remission in patients with
      rheumatoid arthritis and psoriatic arthritis: data from the prospective
      multicentre NOR-DMARD study.
AB  - OBJECTIVE: To investigate the predictive value of discordance between (1) tender
      and swollen joint count and (2) patient's and evaluator's global assessment on
      remission in patients with rheumatoid arthritis (RA) and psoriatic arthritis
      (PsA). METHODS: From the prospective, multicentre Norwegian-Disease-Modifying
      Antirheumatic Drug study, we included patients with RA and PsA starting first
      time tumour necrosis factor inhibitors and DMARD-naive patients starting
      methotrexate between 2000 and 2012. The predictive value of DeltaTSJ (tender
      minus swollen joint counts) and DeltaPEG (patient's minus evaluator's global
      assessment) on remission was explored in prespecified logistic regression models
      adjusted for age, sex, disease duration and smoking. RESULTS: A total of 2735
      patients with RA and 1236 patients with PsA were included (mean (SD) age 55.0
      (13.5)/48.3 (12.4) years, median(range) disease duration 0.7 (0.0-58.0)/1.3 (0.0
      48.3) years, 69.7/48.4% females). Baseline DeltaTSJ/DeltaPEG reduced the
      likelihood of achieving DAS28<2.6, SDAI<=3.3, CDAI<=2.8, ACR/EULAR Boolean and
      DAPSA<4 remission after 3 and 6 months in RA (OR 0.95-0.97, p<0.001/OR 0.96-0.99,
      p<=0.01) and PsA (OR 0.91-0.94, p<=0.004/OR 0.89-0.99, p<=0.002), except for
      DeltaPEG and 6-month DAS28 remission in PsA. CONCLUSIONS: Discordance between
      patient's and physician's evaluation of disease activity reflected through
      DeltaTSJ and partly DeltaPEG may reduce likelihood of remission in RA and PsA.
      The findings are relevant for use of the treat-to-target strategy in individual
      patients.

PMID- 27707732
TI  - Tight foreskin.

PMID- 27707733
TI  - Independent or employed? There is a third way. . .

PMID- 27707734
TI  - Compulsory licences for direct acting antiviral drugs for hepatitis C.

PMID- 27707735
TI  - When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the
      genomic box in chronic myelomonocytic leukemia.
AB  - Exome sequencing studies in chronic myelomonocytic leukemia (CMML) illustrate a
      mutational landscape characterized by few somatic mutations involving a subset of
      recurrent gene mutations in ASXL1, SRSF2, and TET2, each approaching 40% in
      incidence. This has led to the clinical implementation of next-generation
      sequencing panels that effectively identify clonal monocytosis and complement
      clinical prognostic scoring systems in most patients. However, most murine models
      based on single gene mutations fail to recapitulate the CMML phenotype, and many
      gene mutations are loss of function, making the identification of traditional
      therapeutic vulnerabilities challenging. Further, as a subtype of the
      myelodysplastic/myeloproliferative neoplasms, CMML has a complex clinical
      heterogeneity not reflected by the mutational landscape. In this review, we will
      discuss the discordance between mutational homogeneity and clinical complexity
      and highlight novel genomic and nongenomic approaches that offer insight into the
      underlying clinical characteristics of CMML.

PMID- 27707737
TI  - Ahmed Kazmi: Turning medicine into comedy.

PMID- 27707736
TI  - Strict in vivo specificity of the Bcl11a erythroid enhancer.
AB  - BCL11A, a repressor of human fetal (gamma-)globin expression, is required for
      immune and hematopoietic stem cell functions and brain development. Regulatory
      sequences within the gene, which are subject to genetic variation affecting fetal
      globin expression, display hallmarks of an erythroid enhancer in cell lines and
      transgenic mice. As such, this enhancer is a novel, attractive target for
      therapeutic gene editing. To explore the roles of such sequences in vivo, we
      generated mice in which the orthologous 10-kb intronic sequences were removed.
      Bcl11a enhancer-deleted mice, Bcl11a(Deltaenh), phenocopy the BCL11A-null state
      with respect to alterations of globin expression, yet are viable and exhibit no
      observable blood, brain, or other abnormalities. These preclinical findings
      provide strong in vivo support for genetic modification of the enhancer for
      therapy of hemoglobin disorders.

PMID- 27707738
TI  - Consensus on Exercise Reporting Template (CERT): Explanation and Elaboration
      Statement.
AB  - Exercise is effective for prevention and management of acute and chronic health
      conditions. However, trial descriptions of exercise interventions are often
      suboptimal, leaving readers unclear about the content of effective programmes. To
      address this, the 16-item internationally endorsed Consensus on Exercise
      Reporting Template (CERT) was developed. The aim is to present the final template
      and provide an Explanation and Elaboration Statement to operationalise the CERT.
      Development of the CERT was based on the EQUATOR Network methodological framework
      for developing reporting guidelines. We used a modified Delphi technique to gain
      consensus of international exercise experts and conducted 3 sequential rounds of
      anonymous online questionnaires and a Delphi workshop. The 16-item CERT is the
      minimum data set considered necessary to report exercise interventions. The
      contents may be included in online supplementary material, published as a
      protocol or located on websites and other electronic repositories. The
      Explanation and Elaboration Statement is intended to enhance the use,
      understanding and dissemination of the CERT and presents the meaning and
      rationale for each item, together with examples of good reporting. The CERT is
      designed specifically for the reporting of exercise programmes across all
      evaluative study designs for exercise research. The CERT can be used by authors
      to structure intervention reports, by reviewers and editors to assess
      completeness of exercise descriptions and by readers to facilitate the use of the
      published information. The CERT has the potential to increase clinical uptake of
      effective exercise programmes, enable research replication, reduce research waste
      and improve patient outcomes.

PMID- 27707739
TI  - Physical activity and exercise for erectile dysfunction: systematic review and
      meta-analysis.
AB  - BACKGROUND: A growing body of evidence suggests that physical activity and
      exercise may improve erectile function. OBJECTIVE: To conduct a systematic review
      and meta-analysis evaluating the effects of physical activity modalities and
      exercise on erectile function in erectile dysfunction trials. METHODS: A
      systematic review was conducted in accordance with the Preferred Reporting Items
      for Systematic Review and Meta-Analyses (PRISMA) statement. We searched 6
      electronic databases between January 1990 and July 2016 and hand-searched
      reference lists for randomised controlled trials. Only patients with a diagnosis
      of erectile dysfunction were included. The mean differences between intervention
      and control groups were calculated for meta-analysis. RESULTS: 7 studies were
      eligible, including 478 participants allocated to aerobic, pelvic or combined
      exercise interventions. Follow-up ranged from 8 weeks to 2 years. The risk of
      bias in the trials was deemed moderate to high mainly due to impossible blinding
      of patients and personnel, as well as questionable blinding of outcome assessors.
      Random-effects meta-analyses were performed. Pooled data showed a statistically
      significant improvement in erectile function score (mean difference 3.85, 95% CI
      2.33 to 5.37). A benefit was still demonstrable after a sensitivity analysis
      because the mean difference in International Index of Erectile Function (IIEF)
      score ranged from 3.39 (95% CI 1.92 to 4.87) to 4.28 (95% CI 2.54 to 6.02). A
      benefit was also detected in short-term and long-term interventions as well as in
      trials evaluating physical activity and exercise alone or in addition to usual
      care. CONCLUSIONS: The present study suggests that physical activity and exercise
      interventions improve patient-reported erectile dysfunction, particularly aerobic
      exercise with moderate-to-vigorous intensity.

PMID- 27707740
TI  - Exercise to prevent falls in older adults: an updated systematic review and meta
      analysis.
AB  - OBJECTIVE: Previous meta-analyses have found that exercise prevents falls in
      older people. This study aimed to test whether this effect is still present when
      new trials are added, and it explores whether characteristics of the trial
      design, sample or intervention are associated with greater fall prevention
      effects. DESIGN: Update of a systematic review with random effects meta-analysis
      and meta-regression. DATA SOURCES: Cochrane Library, CINAHL, MEDLINE, EMBASE,
      PubMed, PEDro and SafetyLit were searched from January 2010 to January 2016.
      STUDY ELIGIBILITY CRITERIA: We included randomised controlled trials that
      compared fall rates in older people randomised to receive exercise as a single
      intervention with fall rates in those randomised to a control group. RESULTS: 99
      comparisons from 88 trials with 19 478 participants were available for meta
      analysis. Overall, exercise reduced the rate of falls in community-dwelling older
      people by 21% (pooled rate ratio 0.79, 95% CI 0.73 to 0.85, p<0.001, I2 47%, 69
      comparisons) with greater effects seen from exercise programmes that challenged
      balance and involved more than 3 hours/week of exercise. These variables
      explained 76% of the between-trial heterogeneity and in combination led to a 39%
      reduction in falls (incident rate ratio 0.61, 95% CI 0.53 to 0.72, p<0.001).
      Exercise also had a fall prevention effect in community-dwelling people with
      Parkinson's disease (pooled rate ratio 0.47, 95% CI 0.30 to 0.73, p=0.001, I2
      65%, 6 comparisons) or cognitive impairment (pooled rate ratio 0.55, 95% CI 0.37
      to 0.83, p=0.004, I2 21%, 3 comparisons). There was no evidence of a fall
      prevention effect of exercise in residential care settings or among stroke
      survivors or people recently discharged from hospital. SUMMARY/CONCLUSIONS:
      Exercise as a single intervention can prevent falls in community-dwelling older
      people. Exercise programmes that challenge balance and are of a higher dose have
      larger effects. The impact of exercise as a single intervention in clinical
      groups and aged care facility residents requires further investigation, but
      promising results are evident for people with Parkinson's disease and cognitive
      impairment.

PMID- 27707742
TI  - Self-report measures in athletic preparation.

PMID- 27707743
TI  - Infographic: AMSSM position statement on cardiovascular preparticipation
      screening in athletes: Current evidence, knowledge gaps, recommendations and
      future directions.

PMID- 27707741
TI  - Injuries among weightlifters and powerlifters: a systematic review.
AB  - BACKGROUND: Olympic weightlifting and powerlifting are two sports that expose the
      body to great forces. Injury characteristics have not been systematically
      reviewed for these two growing sports. OBJECTIVE: The purpose of this study was
      to systematically review the literature regarding various definitions of injuries
      used, injury localisation, the prevalence and incidence of injuries and the
      associated risk factors for injuries in weightlifting and powerlifting. DESIGN:
      Systematic review. DATA SOURCES: Five databases, PubMed, MEDLINE, SPORTDiscus,
      Scopus and Web of Science, were searched between 9 March and 6 April 2015.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies assessing injury incidence
      and prevalence in Olympic weightlifting and powerlifting were included. The
      Quality assessment tool for observational cohort and cross-sectional studies was
      used to assess methodological quality. RESULTS: 9 studies were included in the
      review. Injury was defined fairly consistently across studies. Most studies were
      of low methodological quality. The spine, shoulder and the knee were the most
      common injury localisations in both sports. The injury incidence in weightlifting
      was 2.4-3.3 injuries/1000 hours of training and 1.0-4.4 injuries/1000 hours of
      training in powerlifting. Only one retrospective study had analysed possible risk
      factors. SUMMARY/CONCLUSIONS: The risk of injury in both sports were similar to
      other non-contact sports also requiring strength/power, but low compared to
      contact sports. The severity of injuries differed in the included studies. Since
      little has been studied regarding possible risk factors to injuries, further
      research is therefore warranted to explain why athletes get injured and how to
      prevent injuries. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015014805.

PMID- 27707744
TI  - Can concussion constrain the Caped Crusader?

PMID- 27707745
TI  - What do we need to know about the presidential candidates' health?

PMID- 27707746
TI  - Evaluating physiological responses of plants to salinity stress.
AB  - BACKGROUND: Because soil salinity is a major abiotic constraint affecting crop
      yield, much research has been conducted to develop plants with improved salinity
      tolerance. Salinity stress impacts many aspects of a plant's physiology, making
      it difficult to study in toto Instead, it is more tractable to dissect the
      plant's response into traits that are hypothesized to be involved in the overall
      tolerance of the plant to salinity. SCOPE AND CONCLUSIONS: We discuss how to
      quantify the impact of salinity on different traits, such as relative growth
      rate, water relations, transpiration, transpiration use efficiency, ionic
      relations, photosynthesis, senescence, yield and yield components. We also
      suggest some guidelines to assist with the selection of appropriate experimental
      systems, imposition of salinity stress, and obtaining and analysing relevant
      physiological data using appropriate indices. We illustrate how these indices can
      be used to identify relationships amongst the proposed traits to identify which
      traits are the most important contributors to salinity tolerance. Salinity
      tolerance is complex and involves many genes, but progress has been made in
      studying the mechanisms underlying a plant's response to salinity. Nevertheless,
      several previous studies on salinity tolerance could have benefited from improved
      experimental design. We hope that this paper will provide pertinent information
      to researchers on performing proficient assays and interpreting results from
      salinity tolerance experiments.

PMID- 27707747
TI  - Gene conversion events and variable degree of homogenization of rDNA loci in
      cultivars of Brassica napus.
AB  - BACKGROUND AND AIMS: Brassica napus (AACC, 2n = 38, oilseed rape) is a relatively
      recent allotetraploid species derived from the putative progenitor diploid
      species Brassica rapa (AA, 2n = 20) and Brassica oleracea (CC, 2n = 18). To
      determine the influence of intensive breeding conditions on the evolution of its
      genome, we analysed structure and copy number of rDNA in 21 cultivars of B.
      napus, representative of genetic diversity. METHODS: We used next-generation
      sequencing genomic approaches, Southern blot hybridization, expression analysis
      and fluorescence in situ hybridization (FISH). Subgenome-specific sequences
      derived from rDNA intergenic spacers (IGS) were used as probes for identification
      of loci composition on chromosomes. KEY RESULTS: Most B. napus cultivars (18/21,
      86 %) had more A-genome than C-genome rDNA copies. Three cultivars analysed by
      FISH ('Darmor', 'Yudal' and 'Asparagus kale') harboured the same number (12 per
      diploid set) of loci. In B. napus 'Darmor', the A-genome-specific rDNA probe
      hybridized to all 12 rDNA loci (eight on the A-genome and four on the C-genome)
      while the C-genome-specific probe showed weak signals on the C-genome loci only.
      Deep sequencing revealed high homogeneity of arrays suggesting that the C-genome
      genes were largely overwritten by the A-genome variants in B. napus 'Darmor'. In
      contrast, B. napus 'Yudal' showed a lack of gene conversion evidenced by additive
      inheritance of progenitor rDNA variants and highly localized hybridization
      signals of subgenome-specific probes on chromosomes. Brassica napus 'Asparagus
      kale' showed an intermediate pattern to 'Darmor' and 'Yudal'. At the expression
      level, most cultivars (95 %) exhibited stable A-genome nucleolar dominance while
      one cultivar ('Norin 9') showed co-dominance. CONCLUSIONS: The B. napus cultivars
      differ in the degree and direction of rDNA homogenization. The prevalent
      direction of gene conversion (towards the A-genome) correlates with the direction
      of expression dominance indicating that gene activity may be needed for
      interlocus gene conversion.

PMID- 27707749
TI  - Sixty seconds on . . . posing.

PMID- 27707748
TI  - Control of cytokinin and auxin homeostasis in cyanobacteria and algae.
AB  - BACKGROUND AND AIMS: The metabolism of cytokinins (CKs) and auxins in vascular
      plants is relatively well understood, but data concerning their metabolic
      pathways in non-vascular plants are still rather rare. With the aim of filling
      this gap, 20 representatives of taxonomically major lineages of cyanobacteria and
      algae from Cyanophyceae, Xanthophyceae, Eustigmatophyceae, Porphyridiophyceae,
      Chlorophyceae, Ulvophyceae, Trebouxiophyceae, Zygnematophyceae and
      Klebsormidiophyceae were analysed for endogenous profiles of CKs and auxins and
      some of them were used for studies of the metabolic fate of exogenously applied
      radiolabelled CK, [3H]trans-zeatin (transZ) and auxin ([3H]indole-3-acetic acid
      (IAA)), and the dynamics of endogenous CK and auxin pools during algal growth and
      cell division. METHODS: Quantification of phytohormone levels was performed by
      high-performance or ultrahigh-performance liquid chromatography-electrospray
      tandem mass spectrometry (HPLC-MS/MS, UHPLC-MS/MS). The dynamics of exogenously
      applied [3H]transZ and [3H]IAA in cell cultures were monitored by HPLC with on
      line radioactivity detection. KEY RESULTS: The comprehensive screen of selected
      cyanobacteria and algae for endogenous CKs revealed a predominance of bioactive
      and phosphate CK forms while O- and N-glucosides evidently did not contribute
      greatly to the total CK pool. The abundance of cis-zeatin-type CKs and occurrence
      of CK 2-methylthio derivatives pointed to the tRNA pathway as a substantial
      source of CKs. The importance of the tRNA biosynthetic pathway was proved by the
      detection of tRNA-bound CKs during the course of Scenedesmus obliquus growth.
      Among auxins, free IAA and its oxidation catabolite 2-oxindole-3-acetic acid
      represented the prevailing endogenous forms. After treatment with [3H]IAA, IAA
      aspartate and indole-3-acetyl-1-glucosyl ester were detected as major auxin
      metabolites. Moreover, different dynamics of endogenous CKs and auxin profiles
      during S. obliquus culture clearly demonstrated diverse roles of both
      phytohormones in algal growth and cell division. CONCLUSIONS: Our data suggest
      the existence and functioning of a complex network of metabolic pathways and
      activity control of CKs and auxins in cyanobacteria and algae that apparently
      differ from those in vascular plants.

PMID- 27707750
TI  - Transforming Drug Development in Heart Failure: Navigating the Regulatory
      Crossroads.

PMID- 27707751
TI  - Dilemmas With Race and Heart Failure Treatment.

PMID- 27707752
TI  - Sound-Triggered Production of Antiaggregation Pheromone Limits Overcrowding of
      Dendroctonus valens Attacking Pine Trees.
AB  - For insects that aggregate on host plants, both attraction and antiaggregation
      among conspecifics can be important mechanisms for overcoming host resistance and
      avoiding overcrowding, respectively. These mechanisms can involve multiple
      sensory modalities, such as sound and pheromones. We explored how acoustic and
      chemical signals are integrated by the bark beetle Dendroctonus valens to limit
      aggregation in China. In its native North American range, this insect conducts
      nonlethal attacks on weakened trees at very low densities, but in its introduced
      zone in China, it uses mixtures of host tree compounds and the pheromone
      component frontalin to mass attack healthy trees. We found that exo-brevicomin
      was produced by both female and male D. valens, and that this pheromone
      functioned as an antiaggregating signal. Moreover, beetles feeding in pairs or in
      masses were more likely than were beetles feeding alone to produce exo
      brevicomin, suggesting a potential role of sound by neighboring beetles in
      stimulating exo-brevicomin production. Sound playback showed that an agreement
      sound was produced by both sexes when exposed to the aggregation pheromone
      frontalin and attracts males, and an aggressive sound was produced only by males
      behaving territorially. These signals triggered the release of exo-brevicomin by
      both females and males, indicating an interplay of chemical and sonic
      communication. This study demonstrates that the bark beetle D. valens uses sounds
      to regulate the production of an antiaggregation pheromone, which may provide new
      approaches to pest management of this invasive species.

PMID- 27707753
TI  - MicroRNA-34/449 controls mitotic spindle orientation during mammalian cortex
      development.
AB  - Correct orientation of the mitotic spindle determines the plane of cellular
      cleavage and is crucial for organ development. In the developing cerebral cortex,
      spindle orientation defects result in severe neurodevelopmental disorders, but
      the precise mechanisms that control this important event are not fully
      understood. Here, we use a combination of high-content screening and mouse
      genetics to identify the miR-34/449 family as key regulators of mitotic spindle
      orientation in the developing cerebral cortex. By screening through all
      cortically expressed miRNAs in HeLa cells, we show that several members of the
      miR-34/449 family control mitotic duration and spindle rotation. Analysis of miR
      34/449 knockout (KO) mouse embryos demonstrates significant spindle
      misorientation phenotypes in cortical progenitors, resulting in an excess of
      radial glia cells at the expense of intermediate progenitors and a significant
      delay in neurogenesis. We identify the junction adhesion molecule-A (JAM-A) as a
      key target for miR-34/449 in the developing cortex that might be responsible for
      those defects. Our data indicate that miRNA-dependent regulation of mitotic
      spindle orientation is crucial for cell fate specification during mammalian
      neurogenesis.

PMID- 27707754
TI  - Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute
      Myocardial Infarction.
AB  - BACKGROUND: Interpretation of serial high-sensitivity cardiac troponin (hs-cTn)
      measurements for the diagnosis of acute myocardial infarction (AMI) assumes
      random fluctuation of hs-cTn around an individual's homeostatic set point. The
      aim of this study was to challenge this diagnostic concept. METHODS: Study 1
      examined the presence of a diurnal hs-cTn rhythm by hourly blood sampling, day
      and night, in 24 individuals without a recent history of AMI. Study 2 assessed
      morning vs evening diagnostic accuracy of hs-cTnT and hs-cTnI in a prospective
      multicenter diagnostic study of 2782 unselected patients, presenting to the
      emergency department with acute chest pain. RESULTS: In study 1, hs-cTnT, but not
      hs-cTnI, exhibited a diurnal rhythm, characterized by gradually decreasing
      concentrations throughout daytime, rising concentrations during nighttime, to
      peak concentrations in the morning (mean 16.2 ng/L at 8:30 AM and 12.1 ng/L at
      7:30 PM). In study 2, the hs-cTnT rhythm was confirmed by higher hs-cTnT
      concentrations in early-morning presenters compared to evening presenters with an
      adjudicated diagnosis of noncardiac disease. The diagnostic accuracy [area under
      the receiver-operation characteristics curve (AUC)] of hs-cTnT at presentation, 1
      h, and for the combination of absolute changes with presenting concentration,
      were very high and comparable among patients presenting early morning as compared
      to evening (all AUC >0.93). hs-cTnI exhibited no diurnal rhythm with no
      differences in AUC among early-morning and evening presenters. CONCLUSIONS:
      Rhythmic diurnal variation of hs-cTnT is a general phenomenon that is not seen
      with hs-cTnI. While the diurnal hs-cTnT rhythm does not seem to affect the
      diagnostic accuracy of hs-cTnT for AMI, it should be considered when using hs
      cTnT for screening purposes. CLINICAL TRIAL REGISTRATION: 1. Circadian Variation
      of Cardiac Troponin, NCT02091427, www.clinicaltrials.gov/ct2/show/NCT02091427. 2.
      Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) Study,
      NCT00470587, www.clinicaltrials.gov/ct2/show/NCT00470587.

PMID- 27707756
TI  - Challenging behaviour and learning disabilities: prevention and interventions for
      children with learning disabilities whose behaviour challenges: NICE guideline
      2015.

PMID- 27707755
TI  - Constitutive activation of DIA1 (DIAPH1) via C-terminal truncation causes human
      sensorineural hearing loss.
AB  - DIAPH1 encodes human DIA1, a formin protein that elongates unbranched actin. The
      c.3634+1G>T DIAPH1 mutation causes autosomal dominant nonsyndromic sensorineural
      hearing loss, DFNA1, characterized by progressive deafness starting in childhood.
      The mutation occurs near the C-terminus of the diaphanous autoregulatory domain
      (DAD) of DIA1, which interacts with its N-terminal diaphanous inhibitory domain
      (DID), and may engender constitutive activation of DIA1. However, the underlying
      pathogenesis that causes DFNA1 is unclear. We describe a novel patient-derived
      DIAPH1 mutation (c.3610C>T) in two unrelated families, which results in early
      termination prior to a basic amino acid motif (RRKR1204-1207) at the DAD C
      terminus. The mutant DIA1(R1204X) disrupted the autoinhibitory DID-DAD
      interaction and was constitutively active. This unscheduled activity caused
      increased rates of directional actin polymerization movement and induced
      formation of elongated microvilli. Mice expressing FLAG-tagged DIA1(R1204X)
      experienced progressive deafness and hair cell loss at the basal turn and had
      various morphological abnormalities in stereocilia (short, fused, elongated,
      sparse). Thus, the basic region of the DAD mediates DIA1 autoinhibition;
      disruption of the DID-DAD interaction and consequent activation of DIA1(R1204X)
      causes DFNA1.

PMID- 27707757
TI  - A novel fungal killing mechanism of propionic acid.
AB  - Propionic acid (PPA) is a weak acid that has been used in food products as a
      preservative because of its inhibitory effect on microorganisms. In the present
      study, we investigated the PPA fungal killing mechanism, which showed apoptotic
      features. First, reactive oxygen species (ROS) accumulation and metacaspase
      activation were detected by 2',7'-dichlorodihydrofluorescein diacetate and
      CaspACE FITC-VAD-FMK staining, respectively. Increased fluorescence intensities
      were observed following exposure to PPA, indicating that PPA produced an
      oxidative environment through the generation of ROS and activation of
      metacaspase, which can promote apoptosis signaling. We also examined
      phosphatidylserine externalization (an early apoptosis marker) and DNA and
      nuclear fragmentation (late apoptosis markers) after exposure to PPA. Based on
      the results, we determined that PPA exerts its antifungal effect by inducing
      apoptotic cell death. Moreover, three additional mitochondrial experiments showed
      mitochondrial membrane depolarization, calcium accumulation and cytochrome c
      release after cells were exposed to PPA, indicating that the PPA-induced
      apoptosis pathway is mediated by mitochondria. In conclusion, PPA induces fungal
      cell death through mitochondria-mediated apoptosis. Results of this study
      contribute to a deeper understanding of the preservative effects of PPA.

PMID- 27707759
TI  - A rare case of absent left common carotid artery with bovine origin of the left
      external carotid artery.
AB  - A 22-year-old man had cerebral venous sinus thrombosis and his angiogram
      incidentally revealed an absent left common carotid artery with bovine origin of
      the left external carotid artery. There was also an associated low bifurcation of
      the right common carotid artery and basilar artery fenestration. The absence of a
      common carotid artery is a very rare angiographic finding, and an association
      with a bovine origin of the left external carotid artery has not been reported
      previously in the literature. Here we provide a description of the case along
      with a review of the literature and embryology.

PMID- 27707760
TI  - Small-cell neuroendocrine cancer of the prostate: an atypical presentation of a
      common disease.
AB  - A 70-year-old man with a history of prostate cancer, previously submitted to
      surgical castration and trans-urethral resection of the prostate, was admitted to
      Accident and Emergency department. He had been suffering from osteoarticular and
      abdominal pain, and recent weight loss. An abdominal and a pelvic CT showed
      multiple hepatic metastases and a pelvic mass, but his prostate-specific antigen
      values were low (0.26 n/mL). A biopsy of a hepatic metastasis and of the pelvic
      mass revealed a small-cell neuroendocrine prostate cancer, a rare and aggressive
      androgen-independent form of prostate cancer with a poor prognosis. Our purpose
      was to report a clinical case of a rare and aggressive variant of a common
      disease. A high index of suspicion is required to make an early diagnosis and to
      ensure a proper therapeutic approach.

PMID- 27707763
TI  - Trio of Scientists Wins Lasker Award.
AB  - Gregg L. Semenza, MD, PhD; Peter J. Ratcliffe, MD; and William G. Kaelin Jr., MD,
      will share the 2016 Albert Lasker Basic Medical Research Award. Bestowed by the
      Lasker Foundation, the award recognizes their discovery of the pathway that cells
      use to sense and adapt to changes in availability of oxygen. Such changes can
      play a role in cancer progression and the development of other medical
      conditions.

PMID- 27707762
TI  - Unilateral calf hypertrophy and radiculopathy: an unusual association.

PMID- 27707761
TI  - Management of non-syndromic dens evaginatus affecting permanent maxillary central
      incisors: a systematic review.
AB  - To assess management of non-syndromic dens evaginatus affecting permanent
      maxillary central incisor, we performed a systematic review and also present a
      case report. We searched PubMed via MEDLINE and the reference lists of included
      reports. Eligible studies were any type of clinical studies describing the
      management of non-syndromic dens evaginatus affecting the crown of a permanent
      maxillary central incisor. We included 31 studies corresponding to 34 relevant
      case reports. Therapeutic options were complete reduction of the talon cusp in a
      single appointment (56%), periodic and gradual reduction of the cusp (26%),
      abstention (13%) or extraction (5%). We report an 8-year-old girl with unusual
      two-talon cusp, labial and lingual, on a right maxillary double central incisor.
      A multidisciplinary approach is key to management of permanent maxillary central
      incisors affected by coronary anomalies.

PMID- 27707766
TI  - Disclosing industry ties in articles is not enough.

PMID- 27707764
TI  - Shigella Vaccine Development: Finding the Path of Least Resistance.
AB  - Shigella spp. represent the second most common etiologic pathogen causing
      childhood diarrhea in developing countries. There are no licensed Shigella
      vaccines, and progress for such vaccines has been limited. In this issue of
      Clinical and Vaccine Immunology, Riddle and colleagues (M. S. Riddle, R. W.
      Kaminski, C. Di Paolo, C. K. Porter, R. L. Gutierrez, et al., Clin Vaccine
      Immunol 23:908-917, 2016, http://dx.doi.org/10.1128/CVI.00224-16) report results
      from a phase I study of a parenterally administered monovalent O-polysaccharide
      "bioconjugate" directed against Shigella flexneri 2a. Ultimately, the goal is to
      develop a broad-spectrum Shigella vaccine to address this public health concern.
      A parenteral Shigella vaccine capable of eliciting protection in children of
      developing countries would be an important tool to reach this goal.

PMID- 27707765
TI  - Safety and Immunogenicity of a Parenterally Administered, Structure-Based
      Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine,
      STEBVax.
AB  - Staphylococcus aureus produces several enterotoxins and superantigens, exposure
      to which can elicit profound toxic shock. A recombinant staphylococcal
      enterotoxin B (rSEB) containing 3 distinct mutations in the major
      histocompatibility complex class II binding site was combined with an alum
      adjuvant (Alhydrogel) and used as a potential parenteral vaccine named STEBVax.
      Consenting healthy adult volunteers (age range, 23 to 38 years) participated in a
      first-in-human open-label dose escalation study of parenteral doses of STEBVax
      ranging from 0.01 MUg up to 20 MUg. Safety was assessed by determination of the
      frequency of adverse events and reactogenicity. Immune responses to the
      vaccination were determined by measurement of anti-staphylococcal enterotoxin B
      (anti-SEB) IgG by enzyme-linked immunosorbent assay and a toxin neutralization
      assay (TNA). Twenty-eight participants were enrolled in 7 dosing cohorts. All
      doses were well tolerated. The participants exhibited heterogeneous baseline
      antibody titers. More seroconversions and a faster onset of serum anti-SEB IgG
      toxin-neutralizing antibodies were observed by TNA with increasing doses of
      STEBVax. There was a trend for a plateau in antibody responses with doses of
      STEBVax of between 2.5 and 20 MUg. Among the participants vaccinated with 2.5 MUg
      to 20 MUg of STEBVax, ~93% seroconverted for SEB toxin-neutralizing antibody. A
      strong correlation between individual SEB-specific serum IgG antibody titers and
      the neutralization of gamma interferon production was found in vitro STEBvax
      appeared to be safe and immunogenic, inducing functional toxin-neutralizing
      antibodies. These data support its continued clinical development. (This study
      has been registered at ClinicalTrials.gov under registration no. NCT00974935.).

PMID- 27707767
TI  - Determinants of hypomagnesemia in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Hypomagnesemia (plasma magnesium (Mg2+) concentration <0.7 mmol/L)
      has been described in patients with type 2 diabetes. Polypharmacy is inevitable
      when treating a complex disease such as type 2 diabetes and could explain
      disturbances in the plasma Mg2+ concentration. In this study, we aimed to
      establish the extent of hypomagnesemia in a cohort of type 2 diabetes patients
      and to identify the determinants of plasma Mg2+ levels. METHODS: Patient data and
      samples of 395 type 2 diabetes patients were investigated. Plasma Mg2+
      concentrations were measured using a spectrophotometric assay. Using Pearson
      correlation analyses, variables were correlated to plasma Mg2+ levels. After
      excluding confounding variables, all parameters correlating (P < 0.1) with plasma
      Mg2+ were included in a stepwise backward regression model. RESULTS: The mean
      plasma Mg2+ concentration in this cohort was 0.74 +/- 0.10 mmol/L. In total, 121
      patients (30.6%) suffered from hypomagnesemia. Both plasma triglyceride (r = 
      0.273, P < 0.001) and actual glucose levels (r = -0.231, P < 0.001) negatively
      correlated with the plasma Mg2+ concentration. Patients using metformin (n = 251,
      62%), proton pump inhibitors (n = 179, 45%) or beta-adrenergic receptor agonists
      (n = 31, 8%) displayed reduced plasma Mg2+ levels. Insulin use (n = 299, 76%)
      positively correlated with plasma Mg2+ levels. The model predicted (R2) 20% of
      all variance in the plasma Mg2+ concentration. CONCLUSIONS: Hypomagnesemia is
      highly prevalent in type 2 diabetes patients. Plasma triglycerides and glucose
      levels are major determinants of the plasma Mg2+ concentration, whereas only a
      minor part (<10%) of hypomagnesemia can be explained by drug intake, excluding
      polypharmacy as a major cause for hypomagnesemia in type 2 diabetes.

PMID- 27707768
TI  - Marrow adipose tissue spectrum in obesity and type 2 diabetes mellitus.
AB  - OBJECTIVE: To assess the association of bone mass and marrow adipose tissue (MAT)
      with other fat depots, insulin resistance, bone remodeling markers, adipokines
      and glucose control in type 2 diabetes and obesity. DESIGN AND METHODS: The study
      groups comprised 24 controls (C), 26 obese (O) and 28 type 2 diabetes. Dual
      energy X-ray absorptiometry was used to determine bone mineral density (BMD).
      Blood samples were collected for biochemical measurements. 1H Magnetic resonance
      spectroscopy was used to assess MAT in the L3 vertebra, and abdominal magnetic
      resonance imaging was used to assess intrahepatic lipids in visceral (VAT) and
      subcutaneous adipose tissue. Regression analysis models were used to test the
      association between parameters. RESULTS: At all sites tested, BMD was higher in
      type 2 diabetes than in O and C subjects. The C group showed lower VAT values
      than the type 2 diabetes group and lower IHL than the O and type 2 diabetes
      groups. However, MAT was similar in the 3 groups. Osteocalcin and C-terminal
      telopeptide of type 1 collagen were lower in type 2 diabetes than those in C and
      O subjects. Moreover, at all sites, BMD was negatively associated with
      osteocalcin. No association was observed between MAT and VAT. No relationship was
      observed among MAT and HOMA-IR, leptin, adiponectin or Pref-1, but MAT was
      positively associated with glycated hemoglobin. CONCLUSIONS: MAT is not a niche
      for fat accumulation under conditions of energy surplus and type 2 diabetes, also
      is not associated with VAT or insulin resistance. MAT is associated with glycated
      hemoglobin.

PMID- 27707770
TI  - Milliseconds of Sensory Input Abruptly Modulate the Dynamics of Cortical States
      for Seconds.
AB  - Spontaneous internal activity plays a major role in higher brain functions. The
      question of how it modulates sensory evoked activity and behavior has been
      explored in anesthetized rodents, cats, monkeys and in behaving human subjects.
      However, the complementary question of how a brief sensory input modulates the
      internally generated activity in vivo remains unresolved, and high-resolution
      mapping of these bidirectional interactions was never performed. Integrating
      complementary methodologies, at population and single cells levels, we explored
      this question. Voltage-sensitive dye imaging of population activity in
      anesthetized rats' somatosensory cortex revealed that spontaneous up-states were
      largely diminished for ~2 s, even after a single weak whisker deflection. This
      effect was maximal at the stimulated barrel but spread across several cortical
      areas. A higher velocity whisker deflection evoked activity at ~15Hz. Two-photon
      calcium imaging activity and cell-attached recordings confirmed the VSD results
      and revealed that for several seconds most single cells decreased their firing,
      but a small number increased firing. Comparing single deflection with long train
      stimulation, we found a dominant effect of the first population spike. We suggest
      that, at the onset of a sensory input, some internal messages are silenced to
      prevent overloading of the processing of relevant incoming sensory information.

PMID- 27707769
TI  - Distinct Corticocortical Contributions to Human Precision and Power Grip.
AB  - The corticospinal tract contributes to the control of finger muscles during
      precision and power grip. The involvement of different sets of cortical
      interneuronal circuits during these distinct grasping behaviors remains unknown.
      To examine this question in humans we used noninvasive transcranial magnetic
      stimulation (TMS) over the hand representation of the primary motor cortex to
      elicit motor evoked potentials (MEPs) in an intrinsic finger muscle during index
      finger abduction (control task), precision grip, and power grip. The TMS coil was
      oriented to induce currents in the brain in the latero-medial (LM), posterior
      anterior (PA), and anterior-posterior (AP) direction to preferentially activate
      corticospinal axons directly and early and late synaptic inputs to corticospinal
      neurons, respectively. We found that AP-LM MEP latency differences were
      consistently longer during power grip compared with index finger abduction and
      precision grip, while PA-LM differences remained similar across tasks. Short
      interval intracortical facilitation, targeting AP but not PA inputs, increased
      during power grip compared with other tasks. Our novel findings suggest that
      cortical structures activated by PA and AP stimuli are differentially active
      during precision and power grip. We propose that a preferential recruitment of
      late synaptic inputs to corticospinal neurons may be achieved when humans perform
      a power grip.

PMID- 27707771
TI  - Characterization of 11 Polymorphic Microsatellite Markers for Black Drummer
      (Girella elevata) Developed Using 454 Next-Generation Sequencing.
AB  - Black Drummer (Girella elevata) is a long-lived fish species that experiences
      considerable recreational fishing pressure, although managers lack a clear
      understanding of stock structure and dispersal patterns that are essential for
      the design, implementation, and administration of fisheries stock management. We
      used 454 sequencing to identify and develop 11 microsatellite primer pairs from
      31 G. elevata All loci were found to be polymorphic, with the number of alleles
      detected ranging from 4 to 8 and observed heterozygosity ranging from 0.19 to
      0.87. These markers will be used to assess the genetic diversity and connectivity
      throughout the range of G. elevata, which can assist in the development of
      population management strategies.

PMID- 27707772
TI  - Benchmarking a large regional UK HER2 testing service against current practice
      guidelines.
AB  - AIMS: To critically evaluate HER2 testing data for 3500 consecutive cases over 28
      months for a single laboratory and review these findings in the light of current
      UK reporting guidelines. METHODS: We have reviewed all data relating to the HER2
      testing service including reagents and analytical machine, HER2
      immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) scoring
      profiles. We have examined the place of double counting and rapid screening of
      FISH and when it is and is not safe to do so. This analysis has been facilitated
      greatly by the inclusion of custom scripts embedded in a spreadsheet used for
      recording the data. RESULTS: There were no differences in scoring profiles in
      relation to testing machine or reagent batch for both HER2 IHC and FISH. There
      was excellent concordance in scoring by the biomedical scientists and
      pathologists providing the service. There is a significant difference between the
      proximity of scores in double-scored cases with HER2 copy number >6.0 compared
      with those with copy number <6.00. It is safe to single score with rapid
      screening of HER2 FISH following a first count with a HER2/CEP17 ratio <1.5 and a
      HER2 copy number <3.5. CONCLUSIONS: Single counting of HER2 FISH supported by a
      second rapid screen is safe and practicable within strict parameters. Any
      assessment of proximity of scores in double-scored cases should take into account
      the HER2 copy number, with greater spreads experienced at higher copy numbers.
      Centralising HER2 testing in a regional centre allows detailed audit of the
      entire analytical process.

PMID- 27707773
TI  - Additive effects of dexamethasone and palmitate on hepatic lipid accumulation and
      secretion.
AB  - Synthetic and natural glucocorticoids are able to highly modify liver lipid
      metabolism, which is possibly associated with nonalcoholic fatty liver disease
      development. We have assessed the changes in lipid and sphingolipid contents in
      hepatocytes, lipid composition and saturation status as well as the expression of
      proteins involved in fatty acid transport after both dexamethasone and palmitate
      treatments. The experiments were conducted on primary rat hepatocytes, incubated
      with dexamethasone and/or palmitic acid during short (16 h) and prolonged (40 h)
      exposure. Intracellular and extracellular lipid and sphingolipid contents were
      assessed by gas liquid chromatography and high-performance liquid chromatography,
      respectively. The expression of selected proteins was estimated by Western
      blotting. Short and prolonged exposure to dexamethasone combined with palmitic
      acid resulted in increased expression of fatty acid transporters, which was
      subsequently reflected by excessive intracellular accumulation of
      triacylglycerols and ceramide. The expression of microsomal transfer protein and
      cassette transporter was also significantly increased after dexamethasone and
      palmitate treatment, which was in accordance with elevated extracellular lipid
      and sphingolipid contents. Our data showed additive effects of dexamethasone and
      palmitate on protein-dependent fatty acid uptake in primary hepatocytes,
      resulting in the increased accumulation of triacylglycerols and sphingolipids.
      Moreover, the combined treatment altered fatty acid composition and diminished
      triacylglycerols desaturation index. Importantly, we observed that additive
      effects on both increased microsomal transport protein expression as well as
      elevated export of triacylglycerols, which may be relevant as a liver protective
      mechanism.

PMID- 27707774
TI  - Nitrogen remobilization during leaf senescence: lessons from Arabidopsis to
      crops.
AB  - As a result of climate changes, land use and agriculture have to adapt to new
      demands. Agriculture is responsible for a large part of the greenhouse gas (GHG)
      emissions that have to be urgently reduced in order to protect the environment.
      At the same time, agriculture has to cope with the challenges of sustainably
      feeding a growing world population. Reducing the use of the ammonia-nitrate
      fertilizers that are responsible for a large part of the GHGs released and that
      have a negative impact on carbon balance is one of the objectives of precision
      agriculture. One way to reduce N fertilizers without dramatically affecting grain
      yields is to improve the nitrogen recycling and remobilization performances of
      plants. Mechanisms involved in nitrogen recycling, such as autophagy, are
      essential for nutrient remobilization at the whole-plant level and for seed
      quality. Studies on leaf senescence and nutrient recycling provide new
      perspectives for improvement. The aim of this review is to give an overview of
      the mechanisms involved in nitrogen recycling and remobilization during leaf
      senescence and to present the different approaches undertaken to improve nitrogen
      remobilization efficiency using both model plants and crop species.

PMID- 27707776
TI  - Preventing disease relapses in autoimmune pancreatitis with maintenance steroids:
      are we there yet?

PMID- 27707775
TI  - Robust phenotyping strategies for evaluation of stem non-structural carbohydrates
      (NSC) in rice.
AB  - Rice plants (Oryza sativa) accumulate excess photoassimilates in the form of non
      structural carbohydrates (NSCs) in their stems prior to heading that can later be
      mobilized to supplement photosynthate production during grain-filling. Despite
      longstanding interest in stem NSC for rice improvement, the dynamics of NSC
      accumulation, remobilization, and re-accumulation that have genetic potential for
      optimization have not been systematically investigated. Here we conducted three
      pilot experiments to lay the groundwork for large-scale diversity studies on rice
      stem NSC. We assessed the relationship of stem NSC components with 21 agronomic
      traits in large-scale, tropical yield trials using 33 breeder-nominated lines,
      established an appropriate experimental design for future genetic studies using a
      Bayesian framework to sample sub-datasets from highly replicated greenhouse data
      using 36 genetically diverse genotypes, and used 434 phenotypically divergent
      rice stem samples to develop two partial least-squares (PLS) models using near
      infrared (NIR) spectra for accurate, rapid prediction of rice stem starch,
      sucrose, and total non-structural carbohydrates. We find evidence that stem
      reserves are most critical for short-duration varieties and suggest that pre
      heading stem NSC is worthy of further experimentation for breeding early maturing
      rice.

PMID- 27707777
TI  - Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus
      Report.
AB  - Important progress has been made in the management of Helicobacter pylori
      infection and in this fifth edition of the Maastricht Consensus Report, key
      aspects related to the clinical role of H. pylori were re-evaluated in 2015. In
      the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries
      examined new data related to H. pylori in five subdivided workshops: (1)
      Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public
      Health, (5) H. pylori and the Gastric Microbiota. The results of the individual
      workshops were presented to a final consensus voting that included all
      participants. Recommendations are provided on the basis of the best available
      evidence and relevance to the management of H. pylori infection in the various
      clinical scenarios.

PMID- 27707778
TI  - Urinary Imaging Findings in Young Infants With Bacteremic Urinary Tract
      Infection.
AB  - OBJECTIVES: To describe renal ultrasound (RUS) and voiding cystourethrogram
      (VCUG) findings and determine predictors of abnormal imaging in young infants
      with bacteremic urinary tract infection (UTI). METHODS: We used retrospective
      data from a multicenter sample of infants younger than 3 months with bacteremic
      UTI, defined as the same pathogenic organism in blood and urine. Infants were
      excluded if they had any major comorbidities, known urologic abnormalities at
      time of presentation, required intensive unit care, or had no imaging performed.
      Imaging results as stated in the radiology reports were categorized by a
      pediatric urologist. RESULTS: Of the 276 infants, 19 were excluded. Of the
      remaining 257 infants, 254 underwent a RUS and 224 underwent a VCUG. Fifty-five
      percent had >=1 RUS abnormalities. Thirty-four percent had >=1 VCUG
      abnormalities, including vesicoureteral reflux (VUR, 27%), duplication (1.3%),
      and infravesicular abnormality (0.9%). Age <1 month, male sex, and non
      Escherichia coli organism predicted an abnormal RUS, but only non-E coli organism
      predicted an abnormal VCUG. Seventeen of 96 infants (17.7%) with a normal RUS had
      an abnormal VCUG: 15 with VUR (Grade I-III = 13, Grade IV = 2), 2 with elevated
      postvoid residual, and 1 with infravesical abnormality. CONCLUSIONS: Although RUS
      and VCUG abnormalities were common in this cohort, the frequency and severity
      were similar to previous studies of infants with UTIs in general. Our findings do
      not support special consideration of bacteremia in imaging decisions for
      otherwise well-appearing young infants with UTI.

PMID- 27707779
TI  - The hyperexcitability of dentate granule neurons in organotypic hippocampal slice
      cultures is due to reorganization of synaptic inputs in vitro.
AB  - Organotypic hippocampal slice cultures (OHSCs) provide the experimental
      flexibility of cell culture while leaving much of the natural neuronal
      connectivity intact. Previously, it was shown that the functional and
      morphological features of CA1 pyramidal neurons in OHSCs resemble, to a
      surprising extent, those of CA1 neurons in the acute brain slice preparation.
      However, the extent to which the characteristics of other principle hippocampal
      neurons change or are preserved in cultured slices remains to be determined. In
      the present study, I initially sought to understand whether and how the synaptic
      inputs and morphology of cultured dentate granule neurons (GCs) differ from GCs
      that have developed in vivo. To this end, I compared GCs in OHSCs and GCs in
      acute slices at two equivalent developmental time points (P14 vs. DIV7 and P21
      vs. DIV21). The findings suggest that there is considerable reorganization of
      synaptic input to the organotypic GCs, such that these cells are more susceptible
      to hyperexcitation than GCs in acute slices after 3 weeks. It appears that this
      hyperexcitability emerges through an increase in the proportion of mature
      synapses at proximal dendritic sites and is accompanied by an increase in
      inhibitory neuron activity. These alterations appear to arise in a coordinated
      manner such that the substantial increase in excitatory synaptic drive received
      by the DIV21 GCs in OHSCs remains local and is not translated into excessive
      output possibly leading to damage or major morphological alterations of
      downstream pyramidal neurons.

PMID- 27707780
TI  - Typical gray matter axons in mammalian brain fail to conduct action potentials
      faithfully at fever-like temperatures.
AB  - We studied the ability of typical unmyelinated cortical axons to conduct action
      potentials at fever-like temperatures because fever often gives CNS symptoms. We
      investigated such axons in cerebellar and hippocampal slices from 10 to 25 days
      old rats at temperatures between 30 and 43 degrees C. By recording with two
      electrodes along axonal pathways, we confirmed that the axons were able to
      initiate action potentials, but at temperatures >39 degrees C, the propagation of
      the action potentials to a more distal recording site was reduced. This
      temperature-sensitive conduction may be specific for the very thin unmyelinated
      axons because similar recordings from myelinated CNS axons did not show
      conduction failures. We found that the conduction fidelity improved with 1 mmol/L
      TEA in the bath, probably due to block of voltage-sensitive potassium channels
      responsible for the fast repolarization of action potentials. Furthermore, by
      recording electrically activated antidromic action potentials from the soma of
      cerebellar granule cells, we showed that the axons failed less if they were
      triggered 10-30 msec after another action potential. This was because individual
      action potentials were followed by a depolarizing after-potential, of constant
      amplitude and shape, which facilitated conduction of the following action
      potentials. The temperature-sensitive conduction failures above, but not below,
      normal body temperature, and the failure-reducing effect of the spike's
      depolarizing after-potential, are two intrinsic mechanisms in normal gray matter
      axons that may help us understand how the hyperthermic brain functions.

PMID- 27707781
TI  - Monocyte-to-HDL-cholesterol ratio and left atrial remodelling in atrial
      fibrillation: author's reply.

PMID- 27707782
TI  - Functional improvement after successful catheter ablation for long-standing
      persistent atrial fibrillation.
AB  - Aims: Identifying patients who benefit from restored sinus rhythm (SR) would
      optimize the selection of candidates for ablation of long-standing persistent
      atrial fibrillation (LSPAF). This prospective study sought to identify the
      hitherto unknown factors associated with global functional improvement after
      successful radiofrequency catheter ablation of LSPAF. Methods and results: In 171
      LSPAF patients (84% of the total consecutive 203 patients) who were examined in
      SR 12 months after ablation, the individual per cent change from baseline value
      in maximum oxygen consumption at exercise test (VO2 max), left ventricular
      ejection fraction (LVEF), N-terminal prohormone of brain natriuretic peptide (NT
      proBNP), and five-dimensional descriptive system (EQ-5D) of quality-of-life
      questionnaire were classified in quartiles by 0 (worse) to 3 (best) grades. The
      individual grades were summed into a composite score (SCORE, 0 ... 12) reflecting
      global functional improvement. Significant improvement in VO2 max (3.4 +/- 4.7
      mL/kg/min), LVEF (7.5 +/- 9.1%), NT-proBNP (-861 +/- 809 pg/mL), and EQ-5D (0.7
      +/- 0.12) was observed (all P < 0.0001). On multivariable analysis, younger age
      (P = 0.001), male gender (P = 0.02), timely post-ablation left atrial appendage
      (LAA) outflow (P = 0.005) with improvement in outflow velocity (P = 0.0002), and
      withdrawal of Class I/III antiarrhythmic drugs (P < 0.05) were positively and
      independently correlated with the SCORE. Conclusions: Younger male patients
      benefited most from catheter ablation of LSPAF. Delayed or non-improved LAA
      outflow and inability to discontinue Class I/III antiarrhythmic medication
      reduced the post-ablation functional improvement.

PMID- 27707784
TI  - Improved patient selection for cardiac resynchronization therapy by normalization
      of QRS duration to left ventricular dimension.
AB  - Aims: This study evaluates the relative importance of two components of QRS
      prolongation, myocardial conduction velocity and travel distance of the
      electrical wave front (i.e. path length), for the prediction of acute response to
      cardiac resynchronization therapy (CRT) in left bundle branch block (LBBB)
      patients. Methods and results: Thirty-two CRT candidates (ejection fraction <35%,
      LBBB) underwent cardiac magnetic resonance (CMR) imaging to provide detailed
      information on left ventricular (LV) dimensions. Left ventricular end-diastolic
      volume (LVEDV) was used as a primary measure for path length, subsequently QRSd
      was normalized to LV dimension (i.e. QRSd divided by LVEDV) to adjust for
      conduction path length. Invasive pressure-volume loop analysis at baseline and
      during CRT was used to assess acute pump function improvement, expressed as LV
      stroke work (SW) change. During CRT, SW improved by +38 +/- 46% (P < 0.001). The
      baseline LVEDV was positively related to QRSd (R = 0.36, P = 0.044). Despite this
      association, a paradoxical inverse relation was found between LVEDV and SW
      improvement during CRT (R = -0.40; P = 0.025). Baseline unadjusted QRSd was found
      to be unrelated to SW changes during CRT (R = 0.16; P = 0.383), whereas
      normalized QRSd (QRSd/LVEDV) yielded a strong correlation with CRT response (R =
      0.49; P = 0.005). Other measures of LV dimension, including LV length, LV
      diameter, and LV end-systolic volume, showed similar relations with normalized
      QRSd and SW improvement. Conclusion: Since normalized QRSd reflects myocardial
      conduction properties, these findings suggest that myocardial conduction velocity
      rather than increased path length mainly determines response to CRT. Normalizing
      QRSd to LV dimension might provide a relatively simple method to improve patient
      selection for CRT.

PMID- 27707785
TI  - Outcomes of lead extraction without subsequent device reimplantation.
AB  - Aims: Outcomes among patients who do not receive device reimplantation after
      cardiovascular implantable electronic device (CIED) extraction have not been well
      studied. The present study aims to investigate the outcomes of patients without
      device reimplantation after lead extraction and device removal. Methods and
      results: We retrospectively searched for consecutive patients who underwent CIED
      extraction at Mayo Clinic, Rochester, MN and University of California San Diego
      Medical Center from 2001 through 2012. Among the patients identified, we compared
      characteristics of those who did and did not have device reimplantation. The
      Kaplan-Meier survival was analysed. Among 678 patients, 97 patients had their
      device extracted without reimplantation during 1-year follow-up ('no-reimplant
      group'). Median age was younger in the no-reimplant group (60.7 vs. 70.6 years; P
      < 0.001). The reasons for no reimplantation were as follows: no longer meeting
      criteria for CIED (48%), inappropriate device indication at initial implantation
      (23%), patient preference (17%), and unresolved device complications (12%). Three
      major arrhythmias were reported in the no-reimplant group. Overall survival in
      the no-reimplant group was significantly lower than in the reimplant group (60
      vs. 93%; P < 0.001). Ongoing device-related complications [hazard ratio (HR),
      3.91; 95% CI, 1.74-8.81; P = 0.001], infection (HR, 3.06; 95% CI, 1.24-7.52; P =
      0.02), and concurrent dialysis (HR, 2.74; 95% CI, 1.12-6.71; P = 0.03) were
      associated with increased mortality. Of 31 deaths in the no-reimplant group, 1
      was secondary to cardiac arrhythmia. Conclusion: Fourteen per cent of patients
      who had device extraction did not undergo reimplantation mainly because they no
      longer met CIED indications. The high mortality in these patients is related to
      device complications and comorbid conditions, whereas mortality associated with
      arrhythmia is rare.

PMID- 27707786
TI  - Chemo-Genetic Interactions Between Histone Modification and the Antiproliferation
      Drug AICAR Are Conserved in Yeast and Humans.
AB  - Identifying synthetic lethal interactions has emerged as a promising new
      therapeutic approach aimed at targeting cancer cells directly. Here, we used the
      yeast Saccharomyces cerevisiae as a simple eukaryotic model to screen for
      mutations resulting in a synthetic lethality with 5-amino-4-imidazole carboxamide
      ribonucleoside (AICAR) treatment. Indeed, AICAR has been reported to inhibit the
      proliferation of multiple cancer cell lines. Here, we found that loss of several
      histone-modifying enzymes, including Bre1 (histone H2B ubiquitination) and Set1
      (histone H3 lysine 4 methylation), greatly enhanced AICAR inhibition on growth
      via the combined effects of both the drug and mutations on G1 cyclins. Our
      results point to AICAR impacting on Cln3 subcellular localization and at the Cln1
      protein level, while the bre1 or set1 deletion affected CLN1 and CLN2 expression.
      As a consequence, AICAR and bre1/set1 deletions jointly affected all three G1
      cyclins (Cln1, Cln2, and Cln3), leading to a condition known to result in
      synthetic lethality. Significantly, these chemo-genetic synthetic interactions
      were conserved in human HCT116 cells. Indeed, knock-down of RNF40, ASH2L, and
      KMT2D/MLL2 induced a highly significant increase in AICAR sensitivity. Given that
      KMT2D/MLL2 is mutated at high frequency in a variety of cancers, this synthetic
      lethal interaction has an interesting therapeutic potential.

PMID- 27707787
TI  - The Identification of a Novel Mutant Allele of topoisomerase II in Caenorhabditis
      elegans Reveals a Unique Role in Chromosome Segregation During Spermatogenesis.
AB  - Topoisomerase II alleviates DNA entanglements that are generated during mitotic
      DNA replication, transcription, and sister chromatid separation. In contrast to
      mitosis, meiosis has two rounds of chromosome segregation following one round of
      DNA replication. In meiosis II, sister chromatids segregate from each other,
      similar to mitosis. Meiosis I, on the other hand, segregates homologs, which
      requires pairing, synapsis, and recombination. The exact role that topoisomerase
      II plays during meiosis is unknown. In a screen reexamining Caenorhabditis
      elegans legacy mutants isolated 30 years ago, we identified a novel allele of the
      gene encoding topoisomerase II, top-2(it7). In this study, we demonstrate that
      top-2(it7) males produce dead embryos, even when fertilizing wild-type oocytes.
      Characterization of early embryonic events indicates that fertilization is
      successful and sperm components are transmitted to the embryo. However, sperm
      chromatin is not detected in these fertilized embryos. Examination of top-2(it7)
      spermatogenic germ lines reveals that the sperm DNA fails to segregate properly
      during anaphase I of meiosis, resulting in anucleate sperm. top-2(it7) chromosome
      segregation defects observed during anaphase I are not due to residual
      entanglements incurred during meiotic DNA replication and are not dependent on
      SPO-11-induced double-strand DNA breaks. Finally, we show that TOP-2 associates
      with chromosomes in meiotic prophase and that chromosome association is disrupted
      in the germ lines of top-2(it7) mutants.

PMID- 27707789
TI  - A Randomised, Double-blind, Placebo-controlled Trial of Trichuris suis ova in
      Active Crohn's Disease.
AB  - Background and Aims: To investigate the efficacy and safety of three different
      dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for
      induction of remission in mildly-to-moderately active ileocolonic, uncomplicated
      Crohn's disease [CD]. Methods: Adults with active CD [n = 252] randomly received
      six fortnightly doses of 250, 2500, or 7500 TSO/15 ml suspension/day [TSO 250,
      TSO 2500, TSO 7500], or 15 ml placebo solution/day, in a double-blind fashion,
      with 4 weeks' follow-up. Primary endpoint was the rate of clinical remission
      [Crohn's Disease Activity Index [CDAI] < 150] at end of treatment, ie at Week 12
      or withdrawal. Secondary endpoints included the course of clinical remission,
      rate of clinical response, change in CDAI, change in markers of inflammation,
      mucosal healing, and Physician's Global Assessment. Results: Clinical remission
      at Week 12 occurred in 38.5%, 35.2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500
      patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose
      dependent immunological response. There was no response regarding laboratory
      markers of inflammation. Other secondary efficacy variables also showed no
      advantage of TSO over placebo for treatment of active CD. Administration of TSO
      did not result in any serious adverse drug reaction. Review of non-serious
      suspected adverse drug reactions following TSO did not reveal any safety
      concerns. Conclusions: Administration of 250-7500 TSO fortnightly over 12 weeks
      was safe and showed a dose-dependent immunological response, but no TSO dose
      showed a clinically relevant effect over placebo for induction of clinical
      remission or response in mildly-to-moderately active, ileocolonic CD.

PMID- 27707791
TI  - Image-based teleconsultation using smartphones or tablets: qualitative assessment
      of medical experts.
AB  - BACKGROUND: Mobile health has promising potential in improving healthcare
      delivery by facilitating access to expert advice. Enabling experts to review
      images on their smartphone or tablet may save valuable time. This study aims at
      assessing whether images viewed by medical specialists on handheld devices such
      as smartphones and tablets are perceived to be of comparable quality as when
      viewed on a computer screen. METHODS: This was a prospective study comparing the
      perceived quality of 18 images on three different display devices (smartphone,
      tablet and computer) by 27 participants (4 burn surgeons and 23 emergency
      medicine specialists). The images, presented in random order, covered clinical
      (dermatological conditions, burns, ECGs and X-rays) and non-clinical subjects and
      their perceived quality was assessed using a 7-point Likert scale. Differences in
      devices' quality ratings were analysed using linear regression models for
      clustered data adjusting for image type and participants' characteristics (age,
      gender and medical specialty). RESULTS: Overall, the images were rated good or
      very good in most instances and more so for the smartphone (83.1%, mean score
      5.7) and tablet (78.2%, mean 5.5) than for a standard computer (70.6%, mean 5.2).
      Both handheld devices had significantly higher ratings than the computer screen,
      even after controlling for image type and participants' characteristics. Nearly
      all experts expressed that they would be comfortable using smartphones (n=25) or
      tablets (n=26) for image-based teleconsultation. CONCLUSION: This study suggests
      that handheld devices could be a substitute for computer screens for
      teleconsultation by physicians working in emergency settings.

PMID- 27707788
TI  - Positive Selection in Rapidly Evolving Plastid-Nuclear Enzyme Complexes.
AB  - Rates of sequence evolution in plastid genomes are generally low, but numerous
      angiosperm lineages exhibit accelerated evolutionary rates in similar subsets of
      plastid genes. These genes include clpP1 and accD, which encode components of the
      caseinolytic protease (CLP) and acetyl-coA carboxylase (ACCase) complexes,
      respectively. Whether these extreme and repeated accelerations in rates of
      plastid genome evolution result from adaptive change in proteins (i.e., positive
      selection) or simply a loss of functional constraint (i.e., relaxed purifying
      selection) is a source of ongoing controversy. To address this, we have taken
      advantage of the multiple independent accelerations that have occurred within the
      genus Silene (Caryophyllaceae) by examining phylogenetic and population genetic
      variation in the nuclear genes that encode subunits of the CLP and ACCase
      complexes. We found that, in species with accelerated plastid genome evolution,
      the nuclear-encoded subunits in the CLP and ACCase complexes are also evolving
      rapidly, especially those involved in direct physical interactions with plastid
      encoded proteins. A massive excess of nonsynonymous substitutions between species
      relative to levels of intraspecific polymorphism indicated a history of strong
      positive selection (particularly in CLP genes). Interestingly, however, some
      species are likely undergoing loss of the native (heteromeric) plastid ACCase and
      putative functional replacement by a duplicated cytosolic (homomeric) ACCase.
      Overall, the patterns of molecular evolution in these plastid-nuclear complexes
      are unusual for anciently conserved enzymes. They instead resemble cases of
      antagonistic coevolution between pathogens and host immune genes. We discuss a
      possible role of plastid-nuclear conflict as a novel cause of accelerated
      evolution.

PMID- 27707792
TI  - An ED paradox: patients who arrive by ambulance and then leave without consulting
      an ED provider.
AB  - BACKGROUND: Scientists have called for strategies to identify ED patients with
      unmet needs. We identify the unique profile of ED patients who arrive by
      ambulance and subsequently leave without consulting a provider (ie, a paradoxical
      visit, PV). METHODS: Using a retrospective cohort design, administrative data
      from Winnipeg, Manitoba were interrogated to identify all ED patients 17+ years
      old as having zero, single or multiple PVs in 2012/2013. Analyses compare the
      sociodemographic, physical (eg, arthritis), mental (eg, substance abuse) and
      concurrent healthcare use profile of non-PV, single and multiple PV patients.
      RESULTS: The study cohort consisted of 122 639 patients with 250 754 ED visits.
      Across all ED sites, 2.3% of patients (N=2815) made 3387 PVs, comprising 1.4% of
      all ED visits. Descriptively, more single versus non-PV patients lived in urban
      core and lowest-income areas, were frequent ED users generally, were substance
      abusers and had seven plus primary care physician visits. Multiple PV patients
      had a similar but more extreme profile versus their single PV counterparts (eg,
      54.7% of multiple vs 27.4% of single PV patients had substance abuse challenges).
      From multivariate statistics, single versus non-PV patients are defined uniquely
      by their frequent ED use, by their substance abuse, as living in a core and low
      income area, and as having multiple visits with primary care physicians.
      CONCLUSIONS: PV patients have needs that do not align with the acute model of ED
      care. These patients may benefit from a more integrated care approach likely
      involving allied health professionals.

PMID- 27707790
TI  - Landscape of Genomic Alterations in Pituitary Adenomas.
AB  - Purpose: Pituitary adenomas are the second most common primary brain tumor, yet
      their genetic profiles are incompletely understood.Experimental Design: We
      performed whole-exome sequencing of 42 pituitary macroadenomas and matched normal
      DNA. These adenomas included hormonally active and inactive tumors, ones with
      typical or atypical histology, and ones that were primary or recurrent.Results:
      We identified mutations, insertions/deletions, and copy-number alterations.
      Nearly one-third of samples (29%) had chromosome arm-level copy-number
      alterations across large fractions of the genome. Despite such widespread genomic
      disruption, these tumors had few focal events, which is unusual among highly
      disrupted cancers. The other 71% of tumors formed a distinct molecular class,
      with somatic copy number alterations involving less than 6% of the genome. Among
      the highly disrupted group, 75% were functional adenomas or atypical null-cell
      adenomas, whereas 87% of the less-disrupted group were nonfunctional adenomas. We
      confirmed this association between functional subtype and disruption in a
      validation dataset of 87 pituitary adenomas. Analysis of previously published
      expression data from an additional 50 adenomas showed that arm-level alterations
      significantly impacted transcript levels, and that the disrupted samples were
      characterized by expression changes associated with poor outcome in other
      cancers. Arm-level losses of chromosomes 1, 2, 11, and 18 were significantly
      recurrent. No significantly recurrent mutations were identified, suggesting no
      genes are altered by exonic mutations across large fractions of pituitary
      macroadenomas.Conclusions: These data indicate that sporadic pituitary adenomas
      have distinct copy-number profiles that associate with hormonal and histologic
      subtypes and influence gene expression. Clin Cancer Res; 23(7); 1841-51. (c)2016
      AACR.

PMID- 27707794
TI  - A gene regulatory network for apical organ neurogenesis and its spatial control
      in sea star embryos.
AB  - How neural stem cells generate the correct number and type of differentiated
      neurons in appropriate places remains an important question. Although nervous
      systems are diverse across phyla, in many taxa the larva forms an anterior
      concentration of serotonergic neurons, or apical organ. The sea star embryo
      initially has a pan-neurogenic ectoderm, but the genetic mechanism that directs a
      subset of these cells to generate serotonergic neurons in a particular location
      is unresolved. We show that neurogenesis in sea star larvae begins with soxc
      expressing multipotent progenitors. These give rise to restricted progenitors
      that express lhx2/9 soxc- and lhx2/9-expressing cells can undergo both asymmetric
      divisions, allowing for progression towards a particular neural fate, and
      symmetric proliferative divisions. We show that nested concentric domains of gene
      expression along the anterior-posterior (AP) axis, which are observed in a great
      diversity of metazoans, control neurogenesis in the sea star larva by promoting
      particular division modes and progression towards becoming a neuron. This work
      explains how spatial patterning in the ectoderm controls progression of
      neurogenesis in addition to providing spatial cues for neuron location.
      Modification to the sizes of these AP territories provides a simple mechanism to
      explain the diversity of neuron number among apical organs.

PMID- 27707793
TI  - MicroRNA deep sequencing in two adult stem cell populations identifies miR-501 as
      a novel regulator of myosin heavy chain during muscle regeneration.
AB  - MicroRNAs (miRNAs) are important regulators of skeletal muscle regeneration, but
      the underlying mechanisms are still incompletely understood. Here, comparative
      miRNA sequencing analysis of myogenic progenitor cells (MPs) and non-myogenic
      fibroblast-adipocyte progenitors (FAPs) during cardiotoxin (CTX)-induced muscle
      injury uncovered miR-501 as a novel muscle-specific miRNA. miR-501 is an intronic
      miRNA and its expression levels in MPs correlated with its host gene, chloride
      channel, voltage-sensitive 5 (Clcn5). Pharmacological inhibition of miR-501
      dramatically blunted the induction of embryonic myosin heavy chain (MYH3) and, to
      a lesser extent, adult myosin isoforms during muscle regeneration, and promoted
      small-diameter neofibers. An unbiased target identification approach in primary
      myoblasts validated gigaxonin as a target of miR-501 that mimicked the effect of
      miR-501 inhibition on MYH3 expression. In the mdx mouse model, which models a
      pathological disease state, not only was miR-501 induced in regenerating skeletal
      muscle, but also its serum levels were increased, which correlated with the
      disease state of the animals. Our results suggest that miR-501 plays a key role
      in adult muscle regeneration and might serve as a novel serum biomarker for the
      activation of adult muscle stem cells.

PMID- 27707795
TI  - A new mode of mitochondrial transport and polarized sorting regulated by Dynein,
      Milton and Miro.
AB  - Intrinsic cell microtubule (MT) polarity, together with molecular motors and
      adaptor proteins, determines mitochondrial polarized targeting and MT-dependent
      transport. In polarized cells, such as neurons, mitochondrial mobility and
      transport require the regulation of kinesin and dynein by two adaptor proteins,
      Milton and Miro. Recently, we found that dynein heavy chain 64C (Dhc64C) is the
      primary motor protein for both anterograde and retrograde transport of
      mitochondria in the Drosophila bristle. In this study, we show that a molecular
      lesion in the Dhc64C allele that reduced bristle mitochondrial velocity generated
      a variant that acts as a 'slow' dynein in an MT-gliding assay, indicating that
      dynein directly regulates mitochondrial transport. We also showed that in milton
      RNAi flies, mitochondrial flux into the bristle shaft, but not velocity, was
      significantly reduced. Surprisingly, mitochondria retrograde flux, but not net
      velocity, was significantly decreased in miro-RNAi flies. We thus reveal a new
      mode of mitochondrial sorting in polarized cell growth, whereby bi-directional
      mitochondrial transport undertaken exclusively by dynein is regulated by Milton
      in the anterograde direction and by a Miro-dependent switch to the retrograde
      direction.

PMID- 27707797
TI  - Antagonism between beta-catenin and Gata.a sequentially segregates the germ
      layers of ascidian embryos.
AB  - Many animal embryos use nuclear beta-catenin (nbeta-catenin) during the
      segregation of endomesoderm (or endoderm) from ectoderm. This mechanism is thus
      likely to be evolutionarily ancient. In the ascidian embryo, nbeta-catenin
      reiteratively drives binary fate decisions between ectoderm and endomesoderm at
      the 16-cell stage, and then between endoderm and margin (mesoderm and caudal
      neural) at the 32-cell stage. At the 16-cell stage, nbeta-catenin activates
      endomesoderm genes in the vegetal hemisphere. At the same time, nbeta-catenin
      suppresses the DNA-binding activity of a maternal transcription factor, Gata.a,
      through a physical interaction, and Gata.a thereby activates its target genes
      only in the ectodermal lineage. In the present study, we found that this
      antagonism between nbeta-catenin and Gata.a also operates during the binary fate
      switch at the 32-cell stage. Namely, in marginal cells where nbeta-catenin is
      absent, Gata.a directly activates its target, Zic-r.b (ZicL), to specify the
      marginal cell lineages. Thus, the antagonistic action between nbeta-catenin and
      Gata.a is involved in two consecutive stages of germ layer segregation in
      ascidian embryos.

PMID- 27707796
TI  - iDamIDseq and iDEAR: an improved method and computational pipeline to profile
      chromatin-binding proteins.
AB  - DNA adenine methyltransferase identification (DamID) has emerged as an
      alternative method to profile protein-DNA interactions; however, critical issues
      limit its widespread applicability. Here, we present iDamIDseq, a protocol that
      improves specificity and sensitivity by inverting the steps DpnI-DpnII and adding
      steps that involve a phosphatase and exonuclease. To determine genome-wide
      protein-DNA interactions efficiently, we present the analysis tool iDEAR
      (iDamIDseq Enrichment Analysis with R). The combination of DamID and iDEAR
      permits the establishment of consistent profiles for transcription factors, even
      in transient assays, as we exemplify using the small teleost medaka (Oryzias
      latipes). We report that the bacterial Dam-coding sequence induces aberrant
      splicing when it is used with different promoters to drive tissue-specific
      expression. Here, we present an optimization of the sequence to avoid this
      problem. This and our other improvements will allow researchers to use DamID
      effectively in any organism, in a general or targeted manner.

PMID- 27707799
TI  - Highlight-Chaperone Proteins Are Evolution's Helping Hand.

PMID- 27707798
TI  - The GDNF-GFRalpha1 complex promotes the development of hippocampal dendritic
      arbors and spines via NCAM.
AB  - The formation of synaptic connections during nervous system development requires
      the precise control of dendrite growth and synapse formation. Although glial cell
      line-derived neurotrophic factor (GDNF) and its receptor GFRalpha1 are expressed
      in the forebrain, the role of this system in the hippocampus remains unclear.
      Here, we investigated the consequences of GFRalpha1 deficiency for the
      development of hippocampal connections. Analysis of conditional Gfra1 knockout
      mice shows a reduction in dendritic length and complexity, as well as a decrease
      in postsynaptic density specializations and in the synaptic localization of
      postsynaptic proteins in hippocampal neurons. Gain- and loss-of-function assays
      demonstrate that the GDNF-GFRalpha1 complex promotes dendritic growth and
      postsynaptic differentiation in cultured hippocampal neurons. Finally, in vitro
      assays revealed that GDNF-GFRalpha1-induced dendrite growth and spine formation
      are mediated by NCAM signaling. Taken together, our results indicate that the
      GDNF-GFRalpha1 complex is essential for proper hippocampal circuit development.

PMID- 27707800
TI  - Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall
      Inflammation and Thrombus Resolution.
AB  - RATIONALE: Immune cells play an important role during the generation and
      resolution of thrombosis. T cells are powerful regulators of immune and nonimmune
      cell function, however, their role in sterile inflammation in venous thrombosis
      has not been systematically examined. OBJECTIVE: This study investigated the
      recruitment, activation, and inflammatory activity of T cells in deep vein
      thrombosis and its consequences for venous thrombus resolution. METHODS AND
      RESULTS: CD4+ and CD8+ T cells infiltrate the thrombus and vein wall rapidly on
      deep vein thrombosis induction and remain in the tissue throughout the thrombus
      resolution. In the vein wall, recruited T cells largely consist of effector
      memory T (TEM) cells. Using T-cell receptor transgenic reporter mice, we
      demonstrate that deep vein thrombosis-recruited TEM receive an immediate antigen
      independent activation and produce IFN-gamma (interferon) in situ. Mapping
      inflammatory conditions in the thrombotic vein, we identify a set of deep vein
      thrombosis upregulated cytokines and chemokines that synergize to induce antigen
      independent IFN-gamma production in CD4+ and CD8+ TEM cells. Reducing the number
      of TEM cells through a depletion recovery procedure, we show that intravenous TEM
      activation determines neutrophil and monocyte recruitment and delays thrombus
      neovascularization and resolution. Examining T-cell recruitment in human venous
      stasis, we show that superficial varicose veins preferentially contain activated
      memory T cells. CONCLUSIONS: TEM orchestrate the inflammatory response in venous
      thrombosis affecting thrombus resolution.

PMID- 27707804
TI  - Decreased Skeletal Muscle Mass and Risk Factors of Sarcopenic Dysphagia: A
      Prospective Observational Cohort Study.
AB  - Background: Dysphagia is a known risk factor for malnutrition and pneumonia.
      Although sarcopenia is hypothesized to cause dysphagia, its causality remains
      unclear. Thus, this study aimed to investigate causality and the risk factors for
      sarcopenic dysphagia. Methods: We enrolled 95 hospitalized patients aged 65 years
      or older who had restricted oral intake without dysphagia. The skeletal muscle
      index and Functional Oral Intake Scale were used to evaluate muscle mass and
      swallowing ability, respectively. Nutritional status, assessed by body mass
      index, the Mini Nutritional Assessment-Short Form, and energy intake; activity of
      daily living, assessed by the Barthel Index; hand-grip strength; duration of oral
      intake restriction; and cognitive status were measured. Dysphagia (Functional
      Oral Intake Scale <= 5) was determined after 2 months. Results: The participants'
      mean age was 83.2 +/- 8.0 years; 63% were women. Of the surviving 82 patients, 63
      (77%) had sarcopenia and 21 (26%) developed dysphagia, all of whom had sarcopenia
      (p = .002). Most variables were risk factors for dysphagia on univariate
      analysis. Decreased skeletal muscle index (odds ratio [OR] 24.0, 95% confidence
      interval [CI] 3.6-159.0, p = .001), Barthel Index (OR 12.9, 95% CI 2.1-78.4, p =
      .005), and body mass index (OR 11.4, 95% CI 1.8-70.5, p = .009) were independent
      predictors of dysphagia in the multivariate analysis. Conclusion: This study
      provides evidence for sarcopenic dysphagia and its risk factors. Preventive and
      therapeutic interventions require further study.

PMID- 27707801
TI  - Mitochondrial Carriers Link the Catabolism of Hydroxyaromatic Compounds to the
      Central Metabolism in Candida parapsilosis.
AB  - The pathogenic yeast Candida parapsilosis metabolizes hydroxyderivatives of
      benzene and benzoic acid to compounds channeled into central metabolism,
      including the mitochondrially localized tricarboxylic acid cycle, via the 3
      oxoadipate and gentisate pathways. The orchestration of both catabolic pathways
      with mitochondrial metabolism as well as their evolutionary origin is not fully
      understood. Our results show that the enzymes involved in these two pathways
      operate in the cytoplasm with the exception of the mitochondrially targeted 3
      oxoadipate CoA-transferase (Osc1p) and 3-oxoadipyl-CoA thiolase (Oct1p)
      catalyzing the last two reactions of the 3-oxoadipate pathway. The cellular
      localization of the enzymes indicates that degradation of hydroxyaromatic
      compounds requires a shuttling of intermediates, cofactors, and products of the
      corresponding biochemical reactions between cytosol and mitochondria. Indeed, we
      found that yeast cells assimilating hydroxybenzoates increase the expression of
      genes SFC1, LEU5, YHM2, and MPC1 coding for succinate/fumarate carrier, coenzyme
      A carrier, oxoglutarate/citrate carrier, and the subunit of pyruvate carrier,
      respectively. A phylogenetic analysis uncovered distinct evolutionary
      trajectories for sparsely distributed gene clusters coding for enzymes of both
      pathways. Whereas the 3-oxoadipate pathway appears to have evolved by vertical
      descent combined with multiple losses, the gentisate pathway shows a striking
      pattern suggestive of horizontal gene transfer to the evolutionarily distant
      Mucorales.

PMID- 27707802
TI  - Evolutionary Genomics of Peach and Almond Domestication.
AB  - The domesticated almond [Prunus dulcis (L.) Batsch] and peach [P. persica (Mill.)
      D. A. Webb] originated on opposite sides of Asia and were independently
      domesticated ~5000 yr ago. While interfertile, they possess alternate mating
      systems and differ in a number of morphological and physiological traits. Here,
      we evaluated patterns of genome-wide diversity in both almond and peach to better
      understand the impacts of mating system, adaptation, and domestication on the
      evolution of these taxa. Almond has around seven times the genetic diversity of
      peach, and high genome-wide [Formula: see text] values support their status as
      separate species. We estimated a divergence time of ~8 MYA (million years ago),
      coinciding with an active period of uplift in the northeast Tibetan Plateau and
      subsequent Asian climate change. We see no evidence of a bottleneck during
      domestication of either species, but identify a number of regions showing
      signatures of selection during domestication and a significant overlap in
      candidate regions between peach and almond. While we expected gene expression in
      fruit to overlap with candidate selected regions, instead we find enrichment for
      loci highly differentiated between the species, consistent with recent fossil
      evidence suggesting fruit divergence long preceded domestication. Taken together,
      this study tells us how closely related tree species evolve and are domesticated,
      the impact of these events on their genomes, and the utility of genomic
      information for long-lived species. Further exploration of this data will
      contribute to the genetic knowledge of these species and provide information
      regarding targets of selection for breeding application, and further the
      understanding of evolution in these species.

PMID- 27707803
TI  - A novel TRAPPC11 mutation in two Turkish families associated with cerebral
      atrophy, global retardation, scoliosis, achalasia and alacrima.
AB  - BACKGROUND: Triple A syndrome (MIM #231550) is associated with mutations in the
      AAAS gene. However, about 30% of patients with triple A syndrome symptoms but an
      unresolved diagnosis do not harbour mutations in AAAS. OBJECTIVE: Search for
      novel genetic defects in families with a triple A-like phenotype in whom AAAS
      mutations are not detected. METHODS: Genome-wide linkage analysis, whole-exome
      sequencing and functional analyses were used to discover and verify a novel
      genetic defect in two families with achalasia, alacrima, myopathy and further
      symptoms. Effect and pathogenicity of the mutation were verified by cell
      biological studies. RESULTS: We identified a homozygous splice mutation in
      TRAPPC11 (c.1893+3A>G, [NM_021942.5], g.4:184,607,904A>G [hg19]) in four patients
      from two unrelated families leading to incomplete exon skipping and reduction in
      full-length mRNA levels. TRAPPC11 encodes for trafficking protein particle
      complex subunit 11 (TRAPPC11), a protein of the transport protein particle
      (TRAPP) complex. Western blot analysis revealed a dramatic decrease in full
      length TRAPPC11 protein levels and hypoglycosylation of LAMP1. Trafficking
      experiments in patient fibroblasts revealed a delayed arrival of marker proteins
      in the Golgi and a delay in their release from the Golgi to the plasma membrane.
      Mutations in TRAPPC11 have previously been described to cause limb-girdle
      muscular dystrophy type 2S (MIM #615356). Indeed, muscle histology of our
      patients also revealed mild dystrophic changes. Immunohistochemically, beta
      sarcoglycan was absent from focal patches. CONCLUSIONS: The identified novel
      TRAPPC11 mutation represents an expansion of the myopathy phenotype described
      before and is characterised particularly by achalasia, alacrima, neurological and
      muscular phenotypes.

PMID- 27707805
TI  - Telomerase RNA Component Genetic Variants Interact With the Mediterranean Diet
      Modifying the Inflammatory Status and its Relationship With Aging: CORDIOPREV
      Study.
AB  - Background: Leukocyte telomere length (LTL) attrition has been associated with
      age-related diseases. Telomerase RNA Component (TERC) genetic variants have been
      associated with LTL; whereas fatty acids (FAs) can interact with genetic factors
      and influence in aging. We explore whether variability at the TERC gene locus
      interacts with FA profile and two healthy diets (low-fat diet vs Mediterranean
      diet [MedDiet]) modulating LTL, glucose metabolism, and inflammation status in
      coronary heart disease (CHD) patients. Methods: Inflammation status (high
      sensitivity C-reactive protein [hsCRP], glucose metabolism-glucose, insulin, and
      glycated hemoglobin [HbA1c], and homeostasis model assessment of insulin
      resistance [HOMA-IR]), LTL, FAs, and single nucleotide polymorphisms (SNPs) of
      the TERC gene (rs12696304, rs16847897, and rs3772190) were determined in 1,002
      patients from the CORDIOPREV study (NCT00924937). Results: We report an
      interaction of the TERC rs12696304 SNP with monounsaturated fatty acid (MUFA)
      affecting LTL (p interaction = .01) and hsCRP (p interaction = .03). Among
      individuals with MUFA levels above the median, CC individuals showed higher LTL
      and lower hsCRP than G-allele carriers. Moreover, MedDiet interacted with TERC
      rs12696304 SNP (p interaction = .03). Specifically, CC individuals displayed a
      greater decrease in hsCRP than G-allele carriers. These results were not adjusted
      for multiple statistical testing and p less than .05 was considered significant.
      Conclusions: Our findings suggest that the TERC rs12696304 SNP interacts with
      MUFA improving inflammation status and telomere attrition related with CHD.
      Moreover, the MedDiet intervention improves the inflammatory profile in CC
      individuals compared with the G-allele carriers. These interactions could provide
      a right strategy for personalized nutrition in CHD patients.

PMID- 27707807
TI  - Immunogenicity of Varicella Vaccine and Immunologic Predictors of Response in a
      Cohort of Elderly Nursing Home Residents.
AB  - BACKGROUND:  Little is known about the immunogenicity of live-attenuated
      Oka/Merck varicella zoster virus (VZV)-containing vaccine (hereafter, "varicella
      vaccine") in frail nursing homes residents nor about immune phenotypes associated
      with a response. METHODS:  A cohort of 190 frail nursing home residents aged 80
      102 years and a cohort of 50 community-dwelling seniors aged 60-75 years (a
      comparison group) received varicella vaccine. Interferon gamma (IFN-gamma) enzyme
      linked immunospot assays were performed before and 6 weeks after vaccination.
      Cellular markers of immunosenescence were measured in the nursing home elderly.
      RESULTS:  The average number of IFN-gamma spot-forming cells at baseline was
      significantly lower in the elderly nursing home residents than in the community
      dwelling seniors. However, following vaccination, the VZV immune response
      increased in both cohorts, and no difference was noted in the fold difference of
      the response between the 2 cohorts. Upon further examination of the elderly
      nursing home residents, we found that higher frequencies of regulatory T cells
      and cytomegalovirus-specific CD4+ T cells correlated negatively with the
      magnitude of VZV-specific responses. CONCLUSIONS:  The Oka/Merck varicella
      vaccine induces VZV immunity in elderly nursing home residents that is similar to
      that produced in community-dwelling seniors. CLINICAL TRIALS REGISTRATION: 
      NCT01328548.

PMID- 27707806
TI  - Replication of Genome-Wide Association Study Findings of Longevity in White,
      African American, and Hispanic Women: The Women's Health Initiative.
AB  - Background: No study has evaluated whether genetic factors are associated with
      longevity in African Americans or Hispanics, and it is unclear whether genetic
      factors are associated with healthy aging. Methods: In this prospective study, we
      determined whether 14 genetic variants previously associated with longevity in
      genome-wide association studies were associated with survival to ages 85 and 90
      in 11,053 postmenopausal white, African American, and Hispanic women from the
      Women's Health Initiative. The associations of these variants with healthy aging,
      defined as survival to age 85 without chronic diseases or disability, were also
      determined. Results: Among white women, three single nucleotide polymorphisms
      (SNPs) (rs2075650 [TOMM40], rs4420638 [APOC1], and rs429358 [APOE]) were
      significantly associated with survival to 90 years after correction for multiple
      testing (p < .001); rs4420638 and rs429358 were also significantly associated
      with healthy aging (p = .02). In African American women, no SNP was associated
      with longevity. In Hispanic women, 7 SNPs in linkage disequilibrium with a novel
      SNP, rs2149954, recently identified as being associated with increased longevity
      in a European population, were significantly associated with decreased survival
      to age 85 for carriers of the T versus C allele (p = .04). The association with
      decreased longevity was explained by higher risk of coronary heart disease in
      carriers of the T allele. There were no associations between FOXO3A SNPs and
      longevity in the analyses. In a meta-analysis, rs2075650 and rs429358 were
      significantly associated with longevity. Conclusions: Future studies are needed
      to identify novel loci associated with longevity in African American and Hispanic
      women to determine biologic pathways regulating life span in these groups.

PMID- 27707808
TI  - Genomic Characteristics Behind the Spread of Bacteremic Group A Streptococcus
      Type emm89 in Finland, 2004-2014.
AB  - BACKGROUND:  Many countries worldwide have reported increasing numbers of emm89
      group A Streptococcus (GAS) infections during last decade. Pathogen genetic
      factors linked to this increase need assessment. METHODS:  We investigated
      epidemiological characteristics of emm89 GAS bacteremic infections, including 7
      day and 30-day case-fatality rates, in Finland during 2004-2014 and linked them
      to whole-genome sequencing data obtained from corresponding strains. The Fisher
      exact test and exact logistic regression were used to compare differences between
      bacteremic infections due to emm89 GAS belonging to different genetic clades and
      subclades. RESULTS:  Out of 1928 cases of GAS bacteremic infection, 278 were
      caused by emm89 GAS. We identified 2 genetically distinct clades, arbitrarily
      designated clade 2 and clade 3. Both clades were present during 2004-2008, but
      clade 3 increased rapidly from 2009 onward. Six subclades (designated subclades A
      F) were identified within clade 3, based on phylogenetic core genome analysis.
      The case-fatality rate differed significantly between subclades (P < .05), with
      subclade D having the highest 30-day estimated case-fatality rate (19% vs 3%
      14%). CONCLUSIONS:  A new emm89 clone, clade 3, emerged in 2009 and spread
      rapidly in Finland. Patients infected with certain subclades of clade 3 were
      significantly more likely to die. A specific polymerase chain reaction assay was
      developed to follow the spread of subclade D in 2015.

PMID- 27707809
TI  - Whisker row deprivation affects the flow of sensory information through rat
      barrel cortex.
AB  - : Whisker trimming causes substantial reorganization of neuronal response
      properties in barrel cortex. However, little is known about experience-dependent
      rerouting of sensory processing following sensory deprivation. To address this,
      we performed in vivo intracellular recordings from layers 2/3 (L2/3), layer 4
      (L4), layer 5 regular-spiking (L5RS), and L5 intrinsically bursting (L5IB)
      neurons and measured their multiwhisker receptive field at the level of spiking
      activity, membrane potential, and synaptic conductance before and after sensory
      deprivation. We used Chernoff information to quantify the "sensory information"
      contained in the firing patterns of cells in response to spared and deprived
      whisker stimulation. In the control condition, information for flanking-row and
      same-row whiskers decreased in the order L4, L2/3, L5IB, L5RS. However, after
      whisker-row deprivation, spared flanking-row whisker information was reordered to
      L4, L5RS, L5IB, L2/3. Sensory information from the trimmed whiskers was reduced
      and delayed in L2/3 and L5IB neurons, whereas sensory information from spared
      whiskers was increased and advanced in L4 and L5RS neurons. Sensory information
      from spared whiskers was increased in L5IB neurons without a latency change. L5RS
      cells exhibited the largest changes in sensory information content through an
      atypical plasticity combining a significant decrease in spontaneous activity and
      an increase in a short-latency excitatory conductance. NEW & NOTEWORTHY: Sensory
      cortical plasticity is usually quantified by changes in evoked firing rate. In
      this study we quantified plasticity by changes in sensory detection performance
      using Chernoff information and receiver operating characteristic analysis. We
      found that whisker deprivation causes a change in information flow within the
      cortical layers and that layer 5 regular-spiking cells, despite showing only a
      small potentiation of short-latency input, show the greatest increase in
      information content for the spared input partly by decreasing their spontaneous
      activity.

PMID- 27707810
TI  - GSG1L regulates the strength of AMPA receptor-mediated synaptic transmission but
      not AMPA receptor kinetics in hippocampal dentate granule neurons.
AB  - : GSG1L is an AMPA receptor (AMPAR) auxiliary subunit that regulates AMPAR
      trafficking and function in hippocampal CA1 pyramidal neurons. However, its
      physiological roles in other types of neurons remain to be characterized. Here,
      we investigated the role of GSG1L in hippocampal dentate granule cells and found
      that GSG1L is important for the regulation of synaptic strength but is not
      critical for the modulation of AMPAR deactivation and desensitization kinetics.
      These data demonstrate a neuronal type-specific role of GSG1L and suggest that
      physiological function of AMPAR auxiliary subunits may vary in different types of
      neurons. NEW & NOTEWORTHY: GSG1L is a newly identified AMPA receptor (AMPAR)
      auxiliary subunit and plays a unique role in the regulation of AMPAR trafficking
      and function in hippocampal CA1 pyramidal neurons. However, its role in the
      regulation of AMPARs in hippocampal dentate granule cells remains to be
      characterized. The current work reveals that GSG1L regulates strength of AMPAR
      mediated synaptic transmission but not the receptor kinetic properties in
      hippocampal dentate granule neurons.

PMID- 27707811
TI  - Specific connectivity between photoreceptors and horizontal cells in the
      zebrafish retina.
AB  - The functional and morphological connectivity between various horizontal cell
      (HC) types (H1, H2, H3, and H4) and photoreceptors was studied in zebrafish
      retina. Since HCs are strongly coupled by gap junctions and feedback from HCs to
      photoreceptors depends strongly on connexin (Cx) hemichannels, we characterized
      the various HC Cxs (Cx52.6, Cx52.7, Cx52.9, and Cx55.5) in Xenopus oocytes. All
      Cxs formed hemichannels that were conducting at physiological membrane
      potentials. The Cx hemichannels differed in kinetic properties and voltage
      dependence, allowing for specific tuning of the coupling of HCs and the feedback
      signal from HCs to cones. The morphological connectivity between HC layers and
      cones was determined next. We used zebrafish expressing green fluorescent protein
      under the control of Cx promoters. We found that all HCs showed Cx55.5 promoter
      activity. Cx52.7 promoter activity was exclusively present in H4 cells, while
      Cx52.9 promoter activity occurred only in H1 cells. Cx52.6 promoter activity was
      present in H4 cells and in the ventral quadrant of the retina also in H1 cells.
      Finally, we determined the spectral sensitivities of the HC layers. Three
      response types were found. Monophasic responses were generated by HCs that
      contacted all cones (H1 cells), biphasic responses were generated by HCs that
      contacted M, S, and UV cones (H2 cells), and triphasic responses were generated
      by HCs that contacted either S and UV cones (H3 cells) or rods and UV cones (H4
      cells). Electron microscopy confirms that H4 cells innervate cones. This
      indicates that rod-driven HCs process spectral information during photopic and
      luminance information during scotopic conditions.

PMID- 27707812
TI  - Spontaneous activity is correlated with coding density in primary auditory
      cortex.
AB  - Sensory neurons across sensory modalities and specific processing areas have
      diverse levels of spontaneous firing rates (SFRs) in the absence of sensory
      stimuli. However, the functional significance of this spontaneous activity is not
      well-understood. Previous studies in the auditory system have demonstrated that
      different levels of spontaneous activity are correlated with a variety of
      physiological and anatomic properties, suggesting that neurons with differing
      SFRs make unique contributions to the encoding of auditory stimuli. Additionally,
      altered SFRs are a correlate of tinnitus, arising in several auditory areas after
      exposure to ototoxic substances and noise trauma. In this study, we recorded
      single-unit activity from primary auditory cortex of awake marmoset monkeys while
      delivering wide-band random-spectrum stimuli and white Gaussian noise (WGN) to
      examine any divergences in stimulus encoding properties across SFR classes. We
      found that higher levels of spontaneous activity were associated with both higher
      levels of activation relative to suppression across a variety of wide-band
      stimuli and higher driven rates in response to WGN. Moreover, response latencies
      to WGN were negatively correlated with the level of activation in response to
      both stimulus types. These findings are consistent with a novel view of the role
      spontaneous spiking may play during normal stimulus processing in primary
      auditory cortex and how it may malfunction in cases of tinnitus.

PMID- 27707814
TI  - Acetaminophen study yields new insights into neurobiological underpinnings of
      empathy.
AB  - Empathy is a cornerstone of social behavior, impairments of which are
      characteristic of neuropsychiatric disorders such as autism and psychopathy.
      According to the "shared representations" theory, empathy relies on neural
      processes similar to those underpinning the first-hand experience of a given
      emotion. A recent study by Mischkowski, Crocker, and Way (Soc Cogn Affect
      Neurosci 11: 1345-1353, 2016) provides novel insights into neurobiological
      underpinnings of empathy by demonstrating that acetaminophen, a widely used
      painkiller, reduces empathy for other's physical and social pain.

PMID- 27707813
TI  - Neural tracking of attended versus ignored speech is differentially affected by
      hearing loss.
AB  - : Hearing loss manifests as a reduced ability to understand speech, particularly
      in multitalker situations. In these situations, younger normal-hearing listeners'
      brains are known to track attended speech through phase-locking of neural
      activity to the slow-varying envelope of the speech. This study investigates how
      hearing loss, compensated by hearing aids, affects the neural tracking of the
      speech-onset envelope in elderly participants with varying degree of hearing loss
      (n = 27, 62-86 yr; hearing thresholds 11-73 dB hearing level). In an active
      listening task, a to-be-attended audiobook (signal) was presented either in quiet
      or against a competing to-be-ignored audiobook (noise) presented at three
      individualized signal-to-noise ratios (SNRs). The neural tracking of the to-be
      attended and to-be-ignored speech was quantified through the cross-correlation of
      the electroencephalogram (EEG) and the temporal envelope of speech. We primarily
      investigated the effects of hearing loss and SNR on the neural envelope tracking.
      First, we found that elderly hearing-impaired listeners' neural responses
      reliably track the envelope of to-be-attended speech more than to-be-ignored
      speech. Second, hearing loss relates to the neural tracking of to-be-ignored
      speech, resulting in a weaker differential neural tracking of to-be-attended vs.
      to-be-ignored speech in listeners with worse hearing. Third, neural tracking of
      to-be-attended speech increased with decreasing background noise. Critically, the
      beneficial effect of reduced noise on neural speech tracking decreased with
      stronger hearing loss. In sum, our results show that a common sensorineural
      processing deficit, i.e., hearing loss, interacts with central attention
      mechanisms and reduces the differential tracking of attended and ignored speech.
      NEW & NOTEWORTHY: The present study investigates the effect of hearing loss in
      older listeners on the neural tracking of competing speech. Interestingly, we
      observed that whereas internal degradation (hearing loss) relates to the neural
      tracking of ignored speech, external sound degradation (ratio between attended
      and ignored speech; signal-to-noise ratio) relates to tracking of attended
      speech. This provides the first evidence for hearing loss affecting the ability
      to neurally track speech.

PMID- 27707815
TI  - Secondary generalization of focal-onset seizures: examining the relationship
      between seizure propagation and epilepsy surgery outcome.
AB  - Surgical intervention often fails to achieve seizure-free results in patients
      with intractable epilepsy. Identifying features of the epileptic brain that
      dispose certain patients to unfavorable outcomes is critical for improving
      surgical candidacy assessments. Recent research by Martinet, Ahmad, Lepage, Cash,
      and Kramer (J Neurosci 35: 9477-9490, 2015) suggests that pathways of secondary
      seizure generalization distinguish patients with favorable (i.e., seizure free)
      vs. unfavorable (i.e., seizure persistent) surgical outcomes, lending insights
      into the network mechanisms of epilepsy surgery failure.

PMID- 27707816
TI  - Dose-dependent effects of siRNA-mediated inhibition of SCAP on PCSK9, LDLR, and
      plasma lipids in mouse and rhesus monkey.
AB  - SREBP cleavage-activating protein (SCAP) is a key protein in the regulation of
      lipid metabolism and a potential target for treatment of dyslipidemia. SCAP is
      required for activation of the transcription factors SREBP-1 and -2. SREBPs
      regulate the expression of genes involved in fatty acid and cholesterol
      biosynthesis, and LDL-C clearance through the regulation of LDL receptor (LDLR)
      and PCSK9 expression. To further test the potential of SCAP as a novel target for
      treatment of dyslipidemia, we used siRNAs to inhibit hepatic SCAP expression and
      assess the effect on PCSK9, LDLR, and lipids in mice and rhesus monkeys. In mice,
      robust liver Scap mRNA knockdown (KD) was achieved, accompanied by dose-dependent
      reduction in SREBP-regulated gene expression, de novo lipogenesis, and plasma
      PCSK9 and lipids. In rhesus monkeys, over 90% SCAP mRNA KD was achieved resulting
      in approximately 75, 50, and 50% reduction of plasma PCSK9, TG, and LDL-C,
      respectively. Inhibition of SCAP function was demonstrated by reduced expression
      of SREBP-regulated genes and de novo lipogenesis. In conclusion, siRNA-mediated
      inhibition of SCAP resulted in a significant reduction in circulating PCSK9 and
      LDL-C in rodent and primate models supporting SCAP as a novel target for the
      treatment of dyslipidemia.

PMID- 27707817
TI  - Effect of evolocumab on cholesterol synthesis and absorption.
AB  - The effects of cholesterol-lowering drugs, including those that reduce
      cholesterol synthesis (statins) and those that reduce cholesterol absorption
      (ezetimibe), on cholesterol absorption and synthesis are well understood.
      Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel
      class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C),
      but little is known about their effects on cholesterol absorption and synthesis.
      We evaluated how treatment with evolocumab, a fully human monoclonal IgG2
      antibody to PCSK9, affects markers of cholesterol synthesis and absorption by
      measuring these markers in patients from an evolocumab clinical trial. At 2
      weeks, changes in beta-sitosterol/total cholesterol (TC) from baseline were 4%
      for placebo, 10% for evolocumab 140 mg (nonsignificant vs. placebo), and 26% for
      evolocumab 420 mg (P < 0.001 vs. placebo). Changes in campesterol/TC at week 2,
      relative to baseline between placebo and evolocumab, were all nonsignificant.
      Evolocumab had a modest effect on markers of cholesterol synthesis. At 2 weeks,
      changes in desmosterol/TC were 1% for placebo, 7% for evolocumab 140 mg
      (nonsignificant vs. placebo), and 15% for evolocumab 420 mg (P < 0.01 vs.
      placebo). Changes from baseline in lathosterol/TC at week 2 between placebo and
      evolocumab were nonsignificant. These results suggest that evolocumab has a
      modest effect on cholesterol synthesis and absorption despite significant LDL-C
      lowering.

PMID- 27707818
TI  - Monoacylglycerol-enriched oil increases EPA/DHA delivery to circulatory system in
      humans with induced lipid malabsorption conditions.
AB  - It was hypothesized that under induced lipid malabsorption/maldigestion
      conditions, an enriched sn-1(3)-monoacylglycerol (MAG) oil may be a better
      carrier for n-3 long-chain PUFAs (LC-PUFAs) compared with triacylglycerol (TAG)
      from fish oil. This monocentric double blinded clinical trial examined the
      accretion of EPA (500 mg/day) and DHA (300 mg/day) when consumed as TAG or MAG,
      into the erythrocytes, plasma, and chylomicrons of 45 obese (BMI >=30 kg/m2 and
      <=40 kg/m2) volunteers who were and were not administered Orlistat, an inhibitor
      of pancreatic lipases. Intake of MAG-enriched oil resulted in higher accretion of
      LC-PUFAs than with TAG, the concentrations of EPA and DHA in erythrocytes being,
      respectively, 72 and 24% higher at 21 days (P < 0.001). In addition, MAG
      increased the plasma concentration of EPA by 56% (P < 0.001) as compared with
      TAG. In chylomicrons, MAG intake yielded higher levels of EPA with the area under
      the curve (0-10 h) of EPA being 55% greater (P = 0.012). In conclusion, in obese
      human subjects with Orlistat-induced lipid maldigestion/malabsorption conditions,
      LC-PUFA MAG oil increased LC-PUFA levels in erythrocytes, plasma, and
      chylomicrons to a greater extent than TAG. These results indicate that MAG oil
      might require minimal enzymatic digestion prior to intestinal uptake and transfer
      across the epithelial barrier.

PMID- 27707819
TI  - Toward automated assessment of health Web page quality using the DISCERN
      instrument.
AB  - Background: As the Internet becomes the number one destination for obtaining
      health-related information, there is an increasing need to identify health Web
      pages that convey an accurate and current view of medical knowledge. In response,
      the research community has created multicriteria instruments for reliably
      assessing online medical information quality. One such instrument is DISCERN,
      which measures health Web page quality by assessing an array of features. In
      order to scale up use of the instrument, there is interest in automating the
      quality evaluation process by building machine learning (ML)-based DISCERN Web
      page classifiers. Objective: The paper addresses 2 key issues that are essential
      before constructing automated DISCERN classifiers: (1) generation of a robust
      DISCERN training corpus useful for training classification algorithms, and (2)
      assessment of the usefulness of the current DISCERN scoring schema as a metric
      for evaluating the performance of these algorithms. Methods: Using DISCERN, 272
      Web pages discussing treatment options in breast cancer, arthritis, and
      depression were evaluated and rated by trained coders. First, different consensus
      models were compared to obtain a robust aggregated rating among the coders,
      suitable for a DISCERN ML training corpus. Second, a new DISCERN scoring
      criterion was proposed (features-based score) as an ML performance metric that is
      more reflective of the score distribution across different DISCERN quality
      criteria. Results: First, we found that a probabilistic consensus model applied
      to the DISCERN instrument was robust against noise (random ratings) and superior
      to other approaches for building a training corpus. Second, we found that the
      established DISCERN scoring schema (overall score) is ill-suited to measure ML
      performance for automated classifiers. Conclusion: Use of a probabilistic
      consensus model is advantageous for building a training corpus for the DISCERN
      instrument, and use of a features-based score is an appropriate ML metric for
      automated DISCERN classifiers. Availability: The code for the probabilistic
      consensus model is available at https://bitbucket.org/A_2/em_dawid/ .

PMID- 27707820
TI  - Understanding vasopressor intervention and weaning: risk prediction in a public
      heterogeneous clinical time series database.
AB  - Background: The widespread adoption of electronic health records allows us to ask
      evidence-based questions about the need for and benefits of specific clinical
      interventions in critical-care settings across large populations. Objective: We
      investigated the prediction of vasopressor administration and weaning in the
      intensive care unit. Vasopressors are commonly used to control hypotension, and
      changes in timing and dosage can have a large impact on patient outcomes.
      Materials and Methods: We considered a cohort of 15 695 intensive care unit
      patients without orders for reduced care who were alive 30 days post-discharge. A
      switching-state autoregressive model (SSAM) was trained to predict the
      multidimensional physiological time series of patients before, during, and after
      vasopressor administration. The latent states from the SSAM were used as
      predictors of vasopressor administration and weaning. Results: The unsupervised
      SSAM features were able to predict patient vasopressor administration and
      successful patient weaning. Features derived from the SSAM achieved areas under
      the receiver operating curve of 0.92, 0.88, and 0.71 for predicting ungapped
      vasopressor administration, gapped vasopressor administration, and vasopressor
      weaning, respectively. We also demonstrated many cases where our model predicted
      weaning well in advance of a successful wean. Conclusion: Models that used SSAM
      features increased performance on both predictive tasks. These improvements may
      reflect an underlying, and ultimately predictive, latent state detectable from
      the physiological time series.

PMID- 27707821
TI  - Human resource information systems in health care: a systematic evidence review.
AB  - Objective: This systematic review aimed to: (1) determine the prevalence and
      scope of existing research on human resource information systems (HRIS) in health
      organizations; (2) analyze, classify, and synthesize evidence on the processes
      and impacts of HRIS development, implementation, and adoption; and (3) generate
      recommendations for HRIS research, practice, and policy, with reference to the
      needs of different stakeholders. Methods: A structured search strategy was used
      to interrogate 10 electronic databases indexing research from the health, social,
      management, technology, and interdisciplinary sciences, alongside gray literature
      sources and reference lists of qualifying studies. There were no restrictions on
      language or publication year. Two reviewers screened publications, extracted
      data, and coded findings according to the innovation stages covered in the
      studies. The Critical Appraisal Skills Program checklist was adopted to assess
      study quality. The process of study selection was charted using a Preferred Items
      for Systematic Reviews and Meta-Analysis (PRISMA) diagram. Results: Of the 6824
      publications identified by the search strategy, 68, covering 42 studies, were
      included for final analysis. Research on HRIS in health was interdisciplinary,
      often atheoretical, conducted primarily in the hospital sector of high-income
      economies, and largely focused uncritically on use and realized benefits.
      Discussion and Conclusions: While studies of HRIS in health exist, the overall
      lack of evaluative research raises unanswered questions about their capacity to
      improve quality and efficiency and enable learning health systems, as well as how
      sociotechnical complexity influences implementation and effectiveness. We offer
      this analysis to decision makers and managers considering or currently
      implementing an HRIS, and make recommendations for further research. Trial
      Registration: International Prospective Register of Systematic Reviews
      (PROSPERO): CRD42015023581.
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015023581#.VYu1BPlV
      DU .

PMID- 27707822
TI  - Using social media to monitor mental health discussions - evidence from Twitter.
AB  - Objectives: Given the public health importance of communicating about mental
      illness and the growing use of social media to convey information, our goal was
      to develop an empirical model to identify periods of heightened interest in
      mental health topics on Twitter. Materials and Methods: We collected data on 176
      million tweets from 2011 to 2014 with content related to depression or suicide.
      Using an autoregressive integrated moving average (ARIMA) data analysis, we
      identified deviations from predicted trends in communication about depression and
      suicide. Results: Two types of heightened Twitter activity regarding depression
      or suicide were identified in 2014: expected increases in response to planned
      behavioral health events, and unexpected increases in response to unanticipated
      events. Tweet volume following expected increases went back to the predicted
      level more rapidly than the volume following unexpected events. Discussion:
      Although ARIMA models have been used extensively in other fields, they have not
      been used widely in public health. Our findings indicate that our ARIMA model is
      valid for identifying periods of heightened activity on Twitter related to
      behavioral health. The model offers an objective and empirically based measure to
      identify periods of greater interest for timing the dissemination of credible
      information related to mental health. Conclusion: Spikes in tweet volume
      following a behavioral health event often last for less than 2 days. Individuals
      and organizations that want to disseminate behavioral health messages on Twitter
      in response to heightened periods of interest need to take this limited time
      frame into account.

PMID- 27707823
TI  - Toxoplasma gondii seroprevalence in the Portuguese population: comparison of
      three cross-sectional studies spanning three decades.
AB  - BACKGROUND: Toxoplasma gondii is an obligate intracellular protozoan infecting up
      to one-third of the world's population, constituting a life threat if transmitted
      from mother to child during pregnancy. In Portugal, there is a lack of knowledge
      of the current epidemiological situation, as the unique toxoplasmosis National
      Serological Survey was performed in 1979/1980. METHODS: We studied the
      seroprevalence trends in the Portuguese general population over the past 3
      decades, by assessing chronological spread cross-sectional studies, with special
      focus on women of childbearing age, by age group, region and gender. RESULTS: The
      T. gondii overall seroprevalence decreased from 47% in 1979/1980 to 22% (95% CI
      20% to 24%) in 2013. Generally, we observed that the prevalence of T. gondii IgG
      increased significantly with age and it decreased over time, both in the general
      population and in the childbearing women (18% prevalence in 2013). CONCLUSIONS:
      The scenario observed for the latter indicates that more than 80% of childbearing
      women are susceptible to primary infection yielding a risk of congenital
      toxoplasmosis and respective sequelae. Since there is no vaccine to prevent human
      toxoplasmosis, the improvement of primary prevention constitutes a major tool to
      avoid infection in such susceptible groups.

PMID- 27707825
TI  - Patients' estimations of the importance of preventive health services: a
      nationwide, population-based cross-sectional study in Portugal.
AB  - OBJECTIVES: To determine, in the context of primary care preventive health
      services, the level of importance that Portuguese patients attribute to different
      preventive activities. DESIGN: Cross-sectional study. SETTING: Primary
      Healthcare, Portugal. PARTICIPANTS: 1000 Portuguese adults selected by a
      stratified cluster sampling design were invited to participate in a computer
      assisted telephone survey. Persons with a cognitive or physical disability that
      hampered the ability to complete a telephone interview and being a nursing home
      resident or resident in any other type of collective dwelling were excluded.
      OUTCOMES: Mean level of importance assigned to 20 different medical preventive
      activities, using a scale of 1-10, with 1 corresponding to 'no importance for you
      and your health' and 10 indicating 'very important'. RESULTS: The mean level of
      importance assigned to medical preventive activity was 7.70 (95% CI 7.60 to
      7.80). Routine blood and urine tests were considered the most important, with an
      estimated mean of 9.15 (95% CI 9.07 to 9.24), followed by female-specific
      interventions (Pap smear, mammography and gynaecological and breast ultrasounds),
      with mean importance ranging from 8.45 (95% CI 8.23 to 8.63) for mammography to
      8.56 (95% CI 8.36 to 8.76) for Pap smear. Advice regarding alcohol consumption
      (6.18; 95% CI 5.96 to 6.39) and tobacco consumption (5.99; 95% CI 5.75 to 6.23)
      were considered much less important. CONCLUSIONS: Our results reveal that
      Portuguese patients overestimate the importance of preventive medical activities,
      tend to give more importance to diagnostic and laboratory tests than to lifestyle
      measures, do not discriminate tests that are important and evidence-based, and
      seem not be aware of the individualisation of risk. Family physicians should be
      aware of these optimistic expectations, because these can influence the doctor
      patient relationship when discussing these interventions and incorporating
      personalised risk.

PMID- 27707826
TI  - Symptoms in patients with takotsubo syndrome: a qualitative interview study.
AB  - OBJECTIVE: The aim of the study was to investigate the meaning of narrated
      symptoms in connection to takotsubo syndrome. DESIGN, METHOD, PARTICIPANTS AND
      SETTING: Qualitative study consisting of 25 interviews, 23 women and 2 men aged
      39-84 and living in Region Vastra Gotaland, Sweden. The transcribed text was
      analysed with phenomenological hermeneutics. RESULTS: The interviewees reported a
      large number of symptoms before, during and after the acute onset of takotsubo
      syndrome, including pain, affected breathing, lassitude, malaise and nausea.
      Several of these have not been reported previously. Symptoms before the acute
      onset were, even if they had been prominent, ignored by the interviewees for
      various reasons. During the acute phase, the symptoms could no longer be ignored
      and the interviewees sought healthcare. The remaining residual symptom after
      discharge from hospital caused a great deal of worry because the interviewees
      feared that they would be permanent and they felt they could not live this way.
      On the whole, becoming ill and having a large number of symptoms greatly impacted
      the lives of the interviewees and made them re-evaluate how they had been living.
      Furthermore, they reported feeling alone and lost regarding their symptom burden,
      especially in relation to their residual symptoms, which affected their health
      and ability to return to daily life. CONCLUSIONS: Acute symptoms, and symptoms
      before and after the acute ones, are a major part of the illness experience for
      patients with takotsubo syndrome and affect their health and well-being.
      Assessment of symptoms should be an integrated part of care to promote health.
      One way of achieving this is through the patients' own narratives of their
      experiences, which are an important component in person-centred care.

PMID- 27707824
TI  - Experiences of long-term life-limiting conditions among patients and carers: what
      can we learn from a meta-review of systematic reviews of qualitative studies of
      chronic heart failure, chronic obstructive pulmonary disease and chronic kidney
      disease?
AB  - OBJECTIVES: To summarise and synthesise published qualitative studies to
      characterise factors that shape patient and caregiver experiences of chronic
      heart failure (CHF), chronic obstructive pulmonary disease (COPD) and chronic
      kidney disease (CKD). DESIGN: Meta-review of qualitative systematic reviews and
      metasyntheses. Papers analysed using content analysis. DATA SOURCES: CINAHL,
      EMBASE, MEDLINE, PsychINFO, Scopus and Web of Science were searched from January
      2000 to April 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic
      reviews and qualitative metasyntheses where the participants were patients,
      caregivers and which described experiences of care for CHF, COPD and CKD in
      primary and secondary care who were aged >=18 years. RESULTS: Searches identified
      5420 articles, 53 of which met inclusion criteria. Reviews showed that patients'
      and caregivers' help seeking and decision-making were shaped by their degree of
      structural advantage (socioeconomic status, spatial location, health service
      quality); their degree of interactional advantage (cognitive advantage, affective
      state and interaction quality) and their degree of structural resilience
      (adaptation to adversity, competence in managing care and caregiver response to
      demands). CONCLUSIONS: To the best of our knowledge, this is the first synthesis
      of qualitative systematic reviews in the field. An important outcome of this
      overview is an emphasis on what patients and caregivers value and on attributes
      of healthcare systems, relationships and practices that affect the distressing
      effects and consequences of pathophysiological deterioration in CHF, COPD and
      CKD. Interventions that seek to empower individual patients may have limited
      effectiveness for those who are most affected by the combined weight of
      structural, relational and practical disadvantage identified in this overview. We
      identify potential targets for interventions that could address these
      disadvantages. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42014014547.

PMID- 27707827
TI  - IMproved exercise tolerance in patients with PReserved Ejection fraction by
      Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design
      of the IMPRESS-AF randomised controlled trial.
AB  - INTRODUCTION: Patients with atrial fibrillation frequently suffer from heart
      failure with preserved ejection fraction. At present there is no proven therapy
      to improve physical capacity and quality of life in participants with permanent
      atrial fibrillation with preserved left ventricular contractility. OBJECTIVE: The
      single-centre IMproved exercise tolerance In heart failure With PReserved
      Ejection fraction by Spironolactone On myocardial fibrosiS In Atrial Fibrillation
      (IMPRESS-AF) trial aims to establish whether treatment with spironolactone as
      compared with placebo improves exercise tolerance (cardiopulmonary exercise
      testing), quality of life and diastolic function in patients with permanent
      atrial fibrillation. METHODS AND ANALYSIS: A total of 250 patients have been
      randomised in this double-blinded trial for 2-year treatment with 25 mg daily
      dose of spironolactone or matched placebo. Included participants are 50 years old
      or older, have permanent atrial fibrillation and ejection fraction >55%.
      Exclusion criteria include contraindications to spironolactone, poorly controlled
      hypertension and presence of severe comorbidities with life expectancy <2 years.
      The primary outcome is improvement in exercise tolerance at 2 years and key
      secondary outcomes include quality of life (assessed using the EuroQol EQ-5D-5L
      (EQ-5D) and Minnesota Living with Heart Failure (MLWHF) questionnaires),
      diastolic function and all-cause hospitalisation. ETHICS AND DISSEMINATION: The
      study has been approved by the National Research and Ethics Committee West
      Midlands-Coventry and Warwickshire (REC reference number 14/WM/1211). The results
      of the trial will be published in an international peer-reviewed journal. TRIAL
      REGISTRATION NUMBERS: EudraCT2014-003702-33; NCT02673463; Pre-results.

PMID- 27707828
TI  - Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR): a phase II
      randomised feasibility study of a multidisciplinary rehabilitation package
      following hip fracture.
AB  - OBJECTIVE: To conduct a rigorous feasibility study for a future definitive
      parallel-group randomised controlled trial (RCT) and economic evaluation of an
      enhanced rehabilitation package for hip fracture. SETTING: Recruitment from 3
      acute hospitals in North Wales. Intervention delivery in the community.
      PARTICIPANTS: Older adults (aged >=65) who received surgical treatment for hip
      fracture, lived independently prior to fracture, had mental capacity (assessed by
      clinical team) and received rehabilitation in the North Wales area. INTERVENTION:
      Remote randomisation to usual care (control) or usual care+enhanced
      rehabilitation package (intervention), including six additional home-based
      physiotherapy sessions delivered by a physiotherapist or technical instructor,
      novel information workbook and goal-setting diary. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Primary: Barthel Activities of Daily Living (BADL). Secondary measures
      included Nottingham Extended Activities of Daily Living scale (NEADL), EQ-5D,
      ICECAP capability, a suite of self-efficacy, psychosocial and service-use
      measures and costs. Outcome measures were assessed at baseline and 3-month follow
      up by blinded researchers. RESULTS: 62 participants were recruited, 61 randomised
      (control 32; intervention 29) and 49 (79%) completed 3-month follow-up. Minimal
      differences occurred between the 2 groups for most outcomes, including BADL
      (adjusted mean difference 0.5). The intervention group showed a medium-sized
      improvement in the NEADL relative to the control group, with an adjusted mean
      difference between groups of 3.0 (Cohen's d 0.63), and a trend for greater
      improvement in self-efficacy and mental health, but with small effect sizes. The
      mean cost of delivering the intervention was L231 per patient. There was a small
      relative improvement in quality-adjusted life year in the intervention group. No
      serious adverse events relating to the intervention were reported. CONCLUSIONS:
      The trial methods were feasible in terms of eligibility, recruitment and
      retention. The effectiveness and cost-effectiveness of the rehabilitation package
      should be tested in a phase III RCT. TRIAL REGISTRATION NUMBER: ISRCTN22464643;
      Results.

PMID- 27707830
TI  - Glycaemic control and antidiabetic treatment trends in primary care centres in
      patients with type 2 diabetes mellitus during 2007-2013 in Catalonia: a
      population-based study.
AB  - OBJECTIVES: To assess trends in prescribing practices of antidiabetic agents and
      glycaemic control in patients with type 2 diabetes mellitus (T2DM). DESIGN: Cross
      sectional analysis using yearly clinical data and antidiabetic treatments
      prescribed obtained from an electronic population database. SETTING: Primary
      healthcare centres, including the entire population attended by the Institut
      Catala de la Salut in Catalonia, Spain, from 2007 to 2013. PARTICIPANTS: Patients
      aged 31-90 years with a diagnosis of T2DM. RESULTS: The number of registered
      patients with T2DM in the database was 257 072 in 2007, increasing up to 343 969
      in 2013. The proportion of patients not pharmacologically treated decreased by
      9.7% (95% CI -9.48% to -9.92%), while there was an increase in the percentage of
      patients on monotherapy (4.4% increase; 95% CI 4.16% to 4.64%), combination
      therapy (2.8% increase; 95% CI 2.58% to 3.02%), and insulin alone or in
      combination (increasing 2.5%; 95% CI 2.2% to 2.8%). The use of metformin and
      dipeptidyl peptidase-IV inhibitors increased gradually, while sulfonylureas,
      glitazones and alpha-glucosidase inhibitors decreased. The use of glinides
      remained stable, and the use of glucagon-like peptide-1 receptor agonists was
      still marginal. Regarding glycaemic control, there were no relevant differences
      across years: mean glycated haemoglobin (HbA1c) value was around 7.2%; the
      percentage of patients reaching an HbA1c<=7% target ranged between 52.2% and
      55.6%; and those attaining their individualised target from 72.8% to 75.7%.
      CONCLUSIONS: Although the proportion of patients under pharmacological treatment
      increased substantially over time and there was an increase in the use of
      combination therapies, there have not been relevant changes in glycaemic control
      during the 2007-2013 period in Catalonia.

PMID- 27707829
TI  - Gamification for health promotion: systematic review of behaviour change
      techniques in smartphone apps.
AB  - OBJECTIVE: Smartphone games that aim to alter health behaviours are common, but
      there is uncertainty about how to achieve this. We systematically reviewed health
      apps containing gaming elements analysing their embedded behaviour change
      techniques. METHODS: Two trained researchers independently coded apps for
      behaviour change techniques using a standard taxonomy. We explored associations
      with user ratings and price. DATA SOURCES: We screened the National Health
      Service (NHS) Health Apps Library and all top-rated medical, health and wellness
      and health and fitness apps (defined by Apple and Google Play stores based on
      revenue and downloads). We included free and paid English language apps using
      'gamification' (rewards, prizes, avatars, badges, leaderboards, competitions,
      levelling-up or health-related challenges). We excluded apps targeting health
      professionals. RESULTS: 64 of 1680 (4%) health apps included gamification and met
      inclusion criteria; only 3 of these were in the NHS Library. Behaviour change
      categories used were: feedback and monitoring (n=60, 94% of apps), reward and
      threat (n=52, 81%), and goals and planning (n=52, 81%). Individual techniques
      were: self-monitoring of behaviour (n=55, 86%), non-specific reward (n=49, 82%),
      social support unspecified (n=48, 75%), non-specific incentive (n=49, 82%) and
      focus on past success (n=47, 73%). Median number of techniques per app was 14
      (range: 5-22). Common combinations were: goal setting, self-monitoring, non
      specific reward and non-specific incentive (n=35, 55%); goal setting, self
      monitoring and focus on past success (n=33, 52%). There was no correlation
      between number of techniques and user ratings (p=0.07; rs=0.23) or price (p=0.45;
      rs=0.10). CONCLUSIONS: Few health apps currently employ gamification and there is
      a wide variation in the use of behaviour change techniques, which may limit
      potential to improve health outcomes. We found no correlation between user rating
      (a possible proxy for health benefits) and game content or price. Further
      research is required to evaluate effective behaviour change techniques and to
      assess clinical outcomes. TRIAL REGISTRATION NUMBER: CRD42015029841.

PMID- 27707831
TI  - Comparing physical assessment with administrative data for detecting pressure
      ulcers in a large Canadian academic health sciences centre.
AB  - OBJECTIVE: This study aimed to compare classification of pressure ulcers from
      administrative data with a gold standard assessment, specifically; pressure
      ulcers confirmed by an independent physical assessment performed by trained nurse
      surveyors. SETTING: A retrospective analysis of pooled cross-sectional samples of
      inpatients assessed across 3 consecutive prevalence surveys in a large academic
      health sciences centre between 2012 and 2013. PARTICIPANTS: There were 2001
      patients for whom physical and chart assessments were completed, and for whom a
      discharge abstract was also available at the time of analysis. The cohort's mean
      age was 65 years and 55% were women. RESULTS: Based on the physical assessment
      findings, 14.6% of patients (n=292) had at least 1 pressure ulcer, with a total
      of 345 pressure ulcers documented among these patients: (stage I=162; stage
      II=120; stage III=22; stage IV=22 and unstageable=19). Based on coded
      information, 78 (3.9%) of patients had a pressure ulcer. Of patients with a
      pressure ulcer determined by the physical assessment, only 21% also had a
      pressure ulcer captured in the administrative data. Furthermore, only 6% of the
      patients with a hospital-acquired pressure ulcer, stage II or greater determined
      by the physical assessment were coded in the Discharge Abstract Database (DAD).
      CONCLUSIONS: The results of this study demonstrate that coding in the DAD may
      under-report and fail to accurately reflect the true burden of pressure ulcers in
      hospitalised patients. This may occur because the presence of pressure ulcers is
      currently documented in the health record by nurses and not by physicians, yet
      the administrative data recorded in the DAD only includes physician documented
      pressure ulcers. We recommend enhancements to the coding methods to monitor and
      report on pressure ulcers.

PMID- 27707832
TI  - Readmissions and mortality in delirious versus non-delirious octogenarian
      patients after aortic valve therapy: a prospective cohort study.
AB  - OBJECTIVES: To determine whether postoperative delirium predicts first-time
      readmissions and mortality in octogenarian patients within 180 days after aortic
      valve therapy with surgical aortic valve replacement (SAVR) or transcatheter
      aortic valve implantation (TAVI), and to determine the most common diagnoses at
      readmission. DESIGN: Prospective cohort study of patients undergoing elective
      SAVR or TAVI. SETTING: Tertiary university hospital that performs all SAVRs and
      TAVIs in Western Norway. PARTICIPANTS: Patients 80+ years scheduled for SAVR or
      TAVI and willing to participate in the study were eligible. Those unable to speak
      Norwegian were excluded. Overall, 143 patients were included, and data from 136
      are presented. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was a
      composite variable of time from discharge to first all-cause readmission or
      death. Secondary outcomes were all-cause first readmission alone and mortality
      within 180 days after discharge, and the primary diagnosis at discharge from
      first-time readmission. Delirium was assessed with the confusion assessment
      method. First-time readmissions, diagnoses and mortality were identified in
      hospital information registries. RESULTS: Delirium was identified in 56% of
      patients. The effect of delirium on readmissions and mortality was greatest
      during the first 2 months after discharge (adjusted HR 2.9 (95% CI 1.5 to 5.7)).
      Of 30 first-time readmissions occurring within 30 days, 24 (80%) were patients
      who experienced delirium. 1 patient (non-delirium group) died within 30 days
      after therapy. Delirious patients comprised 35 (64%) of 55 first-time
      readmissions occurring within 180 days. Circulatory system diseases and injuries
      were common causes of first-time readmissions within 180 days in delirious
      patients. 8 patients died 180 days after the procedure; 6 (75%) of them
      experienced delirium. CONCLUSIONS: Delirium in octogenarians after aortic valve
      therapy might be a serious risk factor for postoperative morbidity and mortality.
      Cardiovascular disorders and injuries were associated with first-time
      readmissions in these patients.

PMID- 27707833
TI  - Development and validation of a screening tool for the identification of
      inappropriate transthoracic echocardiograms.
AB  - OBJECTIVE: We sought whether simple clinical markers could be used in a
      questionnaire for recognition of inappropriate (or rarely appropriate, RA) tests
      at point-of-service. Most applications of appropriateness criteria (AC) for
      transthoracic echocardiogram (TTE) have been at the point of order, but a simple
      means of identifying RA tests in an audit process would be of value. DESIGN,
      SETTING AND PARTICIPANTS: The study was performed in 2 major hospitals in
      Tasmania. 2 reviewers created a questionnaire based on 4 questions most commonly
      associated with RA (suspected endocarditis with no positive blood cultures or new
      murmur, lack of cardiovascular symptoms or no change in clinical status or
      cardiac examination, routine surveillance and previous TTE within a year) in a
      derivation cohort of 814 patients. This was prospectively applied to 499 TTEs to
      calculate sensitivity and specificity for prediction of RA, and validated in the
      external group (n=880). RESULTS: Of 499 prospective TTEs, the questionnaire
      selected 18% requests as being potentially RA. As 7.4% were actually RA (kappa
      89%), the sensitivity and specificity of the questionnaire were 84% and 87%,
      respectively. In the external validation cohort, the model found 11% requests
      needed to be screened for appropriateness with a sensitivity and specificity of
      80% and 95%. CONCLUSIONS: A questionnaire based on 4 questions detects a high
      proportion of RA TTE, and could be used for audit.

PMID- 27707834
TI  - Cohort feasibility study of an intermittent pneumatic compression device within a
      below-knee cast for the prevention of venous thromboembolism.
AB  - OBJECTIVES: To determine the likely enrolment rate of eligible participants into
      a randomised controlled trial (RCT) in which a within-cast intermittent pneumatic
      compression device using Jet Impulse Technology (IPC/JIT) is 1 of 3 possible
      interventions in a RCT for the prevention of venous thromboembolism (VTE) in the
      clinical setting of isolated lower limb cast immobilisation. DESIGN: A
      prospective, open-label feasibility study of the IPC/JIT device placed within a
      lower limb cast. SETTING: Wellington Regional Hospital Fracture Clinic.
      PARTICIPANTS: Individuals aged 18-70 who presented with a lower limb injury
      requiring a minimum of 4 weeks below-knee cast immobilisation. INTERVENTION:
      Placement of an IPC/JIT device within lower limb cast. OUTCOME MEASURES: The main
      outcome measure was the proportion of eligible participants who participated in
      the feasibility study. Secondary outcome measures included adherence to device
      usage throughout the study, ease of application of the device and adverse events
      potentially associated with its use. RESULTS: The proportion of potentially
      eligible participants for the IPC/JIT device was only 7/142 (5%), 95% CI 2 to
      9.9. Devices were used for a mean (range) of 4.1 (1.9 to 10.2) hours per day and
      none of 7 participants had adequate adherence to the device. 3 of the 7
      participants suffered an adverse event, including 1 deep vein thrombosis, 2
      dorsal foot ulcer and 1 skin maceration. CONCLUSIONS: A within-cast IPC/JIT
      device is unlikely to be a feasible randomisation arm for a RCT assessing
      possible interventions for the reduction of VTE risk in the clinical setting of
      lower limb injury requiring below knee cast immobilisation for a minimum of 4
      weeks. TRIAL REGISTRATION NUMBER: ANZCTR 12615000192583.

PMID- 27707835
TI  - Examination of psychosocial predictors of Chinese hospital pharmacists' intention
      to provide clinical pharmacy services using the theory of planned behaviour: a
      cross-sectional questionnaire study.
AB  - OBJECTIVES: Main study aim was as follows: (1) to explore the usefulness of the
      theory of planned behaviour (TPB) model in predicting Chinese hospital
      pharmacists' intention to provide clinical pharmacy services (CPSs), including
      auxiliary CPSs and core CPSs; (2) to identify the main factors affecting the
      Chinese hospital pharmacists' intention to provide core CPSs based on TPB
      quantitatively. DESIGN: Cross-sectional questionnaire study. SETTING: The study
      was conducted in 22 general hospitals in seven cities located in the eastern and
      western part of China. PARTICIPANTS: 416 hospital pharmacists (292 (70.2%)
      female) entered and completed the study. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Quantitative responses with hospital pharmacists' intention, attitude, subjective
      norms (SNs) and perceived behavioural control (PBC) over provision of CPSs and
      their past behaviour (PB)-related CPSs. RESULTS: The structural equation model
      analysis found that attitude (p=0.0079, beta=0.12), SN (p=0.038, beta=0.10) and
      the pharmacists' intention to provide auxiliary CPSs (p=0.0001, beta=0.63)
      significantly predicted of their intention to provide core CPSs, accounting for
      54.0% of its variance. Attitude (p=0.0001, beta=0.35), PBC (p=0.0182, beta=0.12)
      and PB (p=0.0009, beta=0.15) are significant predictors of pharmacists'
      intention, accounting for 21% of the variance in pharmacists' intention to
      provide auxiliary CPSs. CONCLUSIONS: The TPB with the addition of PB is a useful
      framework for predicting pharmacists' intention to provide CPSs in Chinese
      hospital care context. Strategies to improve hospital pharmacists' intention to
      provide CPSs should focus on helping the individuals related medical care see the
      value of CPSs, altering their perception of social pressure towards core CPSs and
      the removal of obstacles that impede the translation of intentions into
      behaviour.

PMID- 27707837
TI  - Correction: Establishing crossdiscipline consensus on contraception, pregnancy
      and breast feeding-related educational messages and clinical practices to support
      women with rheumatoid arthritis: an Australian Delphi study.

PMID- 27707836
TI  - Strength Training for Adolescents with cerebral palsy (STAR): study protocol of a
      randomised controlled trial to determine the feasibility, acceptability and
      efficacy of resistance training for adolescents with cerebral palsy.
AB  - INTRODUCTION: Gait is inefficient in children with cerebral palsy, particularly
      as they transition to adolescence. Gait inefficiency may be associated with
      declines in gross motor function and participation among adolescents with
      cerebral palsy. Resistance training may improve gait efficiency through a number
      of biomechanical and neural mechanisms. The aim of the Strength Training for
      Adolescents with cerebral palsy (STAR) trial is to evaluate the effect of
      resistance training on gait efficiency, activity and participation in adolescents
      with cerebral palsy. We also aim to determine the biomechanical and neural
      adaptations that occur following resistance training and evaluate the feasibility
      and acceptability of such an intervention for adolescents with cerebral palsy.
      METHODS AND ANALYSIS: 60 adolescents (Gross Motor Function Classification System
      level I-III) will be randomised to a 10-week resistance training group or a usual
      care control group according to a computer-generated random schedule. The primary
      outcome is gait efficiency. Secondary outcomes are habitual physical activity,
      participation, muscle-tendon mechanics and gross motor function. General linear
      models will be used to evaluate differences in continuous data between the
      resistance training and usual care groups at 10 and 22 weeks, respectively. A
      process evaluation will be conducted alongside the intervention. Fidelity of the
      resistance training programme to trial protocol will be quantified by
      observations of exercise sessions. Semistructured interviews will be conducted
      with participants and physiotherapists following the resistance training
      programme to determine feasibility and acceptability of the programme. ETHICS AND
      DISSEMINATION: This trial has ethical approval from Brunel University London's
      Department of Clinical Sciences' Research Ethics Committee and the National
      Research Ethics Service (NRES) Committee London-Surrey Borders. The results of
      the trial will be submitted for publication in academic journals, presented at
      conferences and distributed to adolescents, families and healthcare professionals
      through the media with the assistance of the STAR advisory group. TRIAL
      REGISTRATION NUMBER: ISRCTN90378161; Pre-results.

PMID- 27707838
TI  - Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA
      Damage in Breast Cancer.
AB  - Background: Previously we identified a DNA damage response-deficient (DDRD)
      molecular subtype within breast cancer. A 44-gene assay identifying this subtype
      was validated as predicting benefit from DNA-damaging chemotherapy. This subtype
      was defined by interferon signaling. In this study, we address the mechanism of
      this immune response and its possible clinical significance. Methods: We used
      immunohistochemistry (IHC) to characterize immune infiltration in 184 breast
      cancer samples, of which 65 were within the DDRD subtype. Isogenic cell lines,
      which represent DDRD-positive and -negative, were used to study the effects of
      chemokine release on peripheral blood mononuclear cell (PBMC) migration and the
      mechanism of immune signaling activation. Finally, we studied the association
      between the DDRD subtype and expression of the immune-checkpoint protein PD-L1 as
      detected by IHC. All statistical tests were two-sided. Results: We found that
      DDRD breast tumors were associated with CD4+ and CD8+ lymphocytic infiltration
      (Fisher's exact test P < .001) and that DDRD cells expressed the chemokines
      CXCL10 and CCL5 3.5- to 11.9-fold more than DNA damage response-proficient cells
      (P < .01). Conditioned medium from DDRD cells statistically significantly
      attracted PBMCs when compared with medium from DNA damage response-proficient
      cells (P < .05), and this was dependent on CXCL10 and CCL5. DDRD cells
      demonstrated increased cytosolic DNA and constitutive activation of the viral
      response cGAS/STING/TBK1/IRF3 pathway. Importantly, this pathway was activated in
      a cell cycle-specific manner. Finally, we demonstrated that S-phase DNA damage
      activated expression of PD-L1 in a STING-dependent manner. Conclusions: We
      propose a novel mechanism of immune infiltration in DDRD tumors, independent of
      neoantigen production. Activation of this pathway and associated PD-L1 expression
      may explain the paradoxical lack of T-cell-mediated cytotoxicity observed in DDRD
      tumors. We provide a rationale for exploration of DDRD in the stratification of
      patients for immune checkpoint-based therapies.

PMID- 27707840
TI  - Semen quality of young adult ICSI offspring: the first results.
AB  - STUDY QUESTION: What is the semen quality of young adult men who were conceived
      18-22 years ago by ICSI for male infertility? SUMMARY ANSWER: In this cohort of
      54 young adult ICSI men, median sperm concentration, total sperm count and total
      motile sperm count were significantly lower than in spontaneously conceived
      peers. WHAT IS KNOWN ALREADY: The oldest ICSI offspring cohort worldwide has
      recently reached adulthood. Hence, their reproductive health can now be
      investigated. Since these children were conceived by ICSI because of severe male
      factor infertility, there is reasonable concern that male offspring have
      inherited the deficient spermatogenesis from their fathers. Previously normal
      pubertal development and adequate Sertoli and Leydig cell function have been
      described in pubertal ICSI boys; however, no information on their sperm quality
      is currently available. STUDY DESIGN, SIZE, DURATION: This study was conducted at
      UZ Brussel between March 2013 and April 2016 and is part of a large follow-up
      project focussing on reproductive and metabolic health of young adults, between
      18 and 22 years and conceived after ICSI with ejaculated sperm. Results of both a
      physical examination and semen analysis were compared between young ICSI men
      being part of a longitudinally followed cohort and spontaneously conceived
      controls who were recruited cross-sectionally. PARTICIPANTS/MATERIALS, SETTING,
      METHOD: Results of a single semen sample in 54 young adult ICSI men and 57
      spontaneously conceived men are reported. All young adults were individually
      assessed, and the results of their physical examination were completed by
      questionnaires. Data were analysed by multiple linear and logistic regression,
      adjusted for covariates. In addition, semen parameters of the ICSI fathers dating
      back from their ICSI treatment application were analysed for correlations. MAIN
      RESULTS AND THE ROLE OF CHANCE: Young ICSI adults had a lower median sperm
      concentration (17.7 million/ml), lower median total sperm count (31.9 million)
      and lower median total motile sperm count (12.7 million) in comparison to
      spontaneously conceived peers (37.0 million/ml; 86.8 million; 38.6 million,
      respectively). The median percentage progressive and total motility, median
      percentage normal morphology and median semen volume were not significantly
      different between these groups. After adjustment for confounders (age, BMI,
      genital malformations, time from ejaculation to analysis, abstinence period), the
      statistically significant differences between ICSI men and spontaneously
      conceived peers remained: an almost doubled sperm concentration in spontaneously
      conceived peers in comparison to ICSI men (ratio 1.9, 95% CI 1.1-3.2) and a two
      fold lower total sperm count (ratio 2.3, 95% CI 1.3-4.1) and total motile count
      (ratio 2.1, 95% CI 1.2-3.6) in ICSI men compared to controls were found.
      Furthermore, compared to men born after spontaneous conception, ICSI men were
      nearly three times more likely to have sperm concentrations below the WHO
      reference value of 15 million/ml (adjusted odds ratio (AOR) 2.7; 95% CI 1.1-6.7)
      and four times more likely to have total sperm counts below 39 million (AOR 4.3;
      95% CI 1.7-11.3). In this small group of 54 father-son pairs, a weak negative
      correlation between total sperm count in fathers and their sons was found.
      LIMITATIONS, REASONS FOR CAUTION: The main limitation is the small study
      population. Also, the results of this study where ICSI was performed with
      ejaculated sperm and for male-factor infertility cannot be generalized to all
      ICSI offspring because the indications for ICSI have nowadays been extended and
      ICSI is also being performed with non-ejaculated sperm and reported differences
      may thus either decrease or increase. WIDER IMPLICATIONS OF THE FINDINGS: These
      first results in a small group of ICSI men indicate a lower semen quantity and
      quality in young adults born after ICSI for male infertility in their fathers.
      STUDY FUNDING/COMPETING INTERESTS: This study was supported by Methusalem grants
      and by grants from Wetenschappelijk Fonds Willy Gepts, all issued by the Vrije
      Universiteit Brussel (VUB). All co-authors except M.B. and H.T. declared no
      conflict of interest. M.B. has received consultancy fees from MSD, Serono
      Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the
      Centre for Medical Genetics have received several educational grants from IBSA,
      Ferring, Organon, Shering-Plough and Merck for establishing the database for
      follow-up research and organizing the data collection. The institution of H.T.
      has received research grants from the Research Fund of Flanders (FWO), an
      unconditional grant from Ferring for research on testicular stem cells and
      research grants from Ferring, Merck, MSD, Roche, Besins, Goodlife and Cook for
      several research projects in female infertility. H.T. has received consultancy
      fees from Finox, Abbott and ObsEva for research projects in female infertility.

PMID- 27707839
TI  - Development of a RNA-Seq Based Prognostic Signature in Lung Adenocarcinoma.
AB  - Background: Precision therapy for lung cancer will require comprehensive genomic
      testing to identify actionable targets as well as ascertain disease prognosis.
      RNA-seq is a robust platform that meets these requirements, but microarray
      derived prognostic signatures are not optimal for RNA-seq data. Thus, we
      undertook the first prognostic analysis of lung adenocarcinoma RNA-seq data and
      generated a prognostic signature. Methods: Lung adenocarcinoma RNA-seq and
      clinical data from The Cancer Genome Atlas (TCGA) were divided chronologically
      into training (n = 255) and validation (n = 157) cohorts. In the training cohort,
      prognostic association was assessed by univariate Cox analysis. A prognostic
      signature was built with stepwise multivariable Cox analysis. Outcomes by risk
      group, stage, and mutation status were analyzed with Kaplan-Meier and
      multivariable Cox analyses. All the statistical tests were two-sided. Results: In
      the training cohort, 96 genes had prognostic association with P values of less
      than or equal to 1.00x10-4, including five long noncoding RNAs (lncRNAs).
      Stepwise regression generated a four-gene signature, including one lncRNA.
      Signature high-risk cases had worse overall survival (OS) in the TCGA validation
      cohort (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 2.00 to 14.62)
      and a University of Michigan institutional cohort (n = 67; HR = 2.05, 95% CI =
      1.18 to 4.55), and worse metastasis-free survival in the TCGA validation cohort
      (HR = 3.05, 95% CI = 2.31 to 13.37). The four-gene prognostic signature also
      statistically significantly stratified overall survival in important clinical
      subsets, including stage I (HR = 2.78, 95% CI = 1.91 to 11.13), EGFR wild-type
      (HR = 3.01, 95% CI = 1.73 to 14.98), and EGFR mutant (HR = 8.99, 95% CI = 62.23
      to 141.44). The four-gene prognostic signature also stood out on top when
      compared with other prognostic signatures. Conclusions: Here, we present the
      first RNA-seq prognostic signature for lung adenocarcinoma that can provide a
      powerful prognostic tool for precision oncology as part of an integrated RNA-seq
      clinical sequencing program.

PMID- 27707841
TI  - Forty years of economic growth and plummeting mortality: the mortality experience
      of the poorly educated in South Korea.
AB  - BACKGROUND: South Korea has experienced rapid economic development and a
      substantial increase in life expectancy in an extremely short period. Whether
      this rapid development has been able to adequately address inequalities in health
      in South Korea may have important policy implications. This paper explores long
      term trends in inequalities in mortality related to education in South Korea
      between 1970 and 2010. METHODS: We used secondary data on population size and
      deaths in 1970 and 1980 from a previously published study, and census and death
      certificate data from Statistics Korea from 1990, 1995, 2000, 2005 and 2010.
      Trends in age-standardised mortality rates for men and women aged 25-64 according
      to education, as well as the rate ratio (RR), rate difference (RD), relative
      index of inequality (RII) and slope index of inequality (SII), were examined over
      the period 1970-2010. RESULTS: Despite overall mortality declines of 70-80% in
      the past 4 decades, educational inequalities have increased or been stagnant.
      There was minimal decline in mortality since 1970 in South Koreans with only a
      primary or lower level of education. The RR and RD between tertiary education and
      primary or lower education increased over the study period, while the RII and the
      SII in both genders remained stable. CONCLUSIONS: The South Korean experience
      over the past 40 years suggests that plummeting mortality rates and huge advances
      in education at the population level do not translate into reduced educational
      inequalities in mortality.

PMID- 27707842
TI  - Brain metastasis reirradiation in patients with advanced breast cancer.
AB  - The outcome of recurrent brain metastasis is dismal. This study aims to assess
      the clinical outcomes and toxicity of reirradiation as a salvage treatment for
      progressive brain metastasis in patients with advanced breast cancer. Between
      July 2005 and September 2014, the medical records of 56 patients with brain
      metastasis from breast cancer were retrospectively reviewed. Of these patients,
      39 received whole-brain radiotherapy (WBRT) followed by stereotactic radiosurgery
      (SRS) reirradiation (Group 1), and 17 received SRS followed by WBRT reirradiation
      (Group 2). Overall survival (OS) and brain progression-free survival rates/times
      were calculated using the Kaplan-Meier method. Prognostic factors were evaluated
      using the Cox proportional hazards model. Change in neurologic function was also
      assessed. The median OS was 10.8 months (range, 1.3-56.8 months). In Group 1, the
      median PFS time (PFS-1) was 6.5 months and the OS time was 11.4 months.
      Multivariate analysis revealed that longer OS was significantly associated with a
      high Karnofsky performance score (KPS) (P = 0.004), controlled extracranial
      metastasis (P = 0.001) and a good response to reirradiation (P = 0.034). In Group
      2, the median PFS time (PFS-2) after reirradiation was 8.5 months and the OS time
      was 10.8 months. Multivariate analysis revealed that longer OS was significantly
      associated with a high KPS (P = 0.018). The majority of the patients had improved
      or stable neurological function. Reirradiation is an effective and a safe
      treatment for patients with brain metastases from breast cancer. It might delay
      the progression of intracranial disease and improve neurological function. A
      suitable patient selection for reirradiation was suggested.

PMID- 27707844
TI  - A Forum for What's Important.

PMID- 27707843
TI  - Adjuvant Therapy for Resected Gallbladder Cancer: Analysis of the National Cancer
      Data Base.
AB  - Background: Management of resected gallbladder cancer relies on single-arm trials
      and retrospective observations. Our objective was to evaluate adjuvant therapy in
      a nationwide data set using causal inference methods to address sources of bias.
      Methods: We studied patients with T2-3 or node-positive, nonmetastatic
      gallbladder cancer, resected with grossly negative margins and reported to the
      National Cancer Data Base between 2004 and 2011. We defined adjuvant therapy as
      any chemotherapy within 90 days of surgery, and upfront concurrent chemoradiation
      as radiation within 14 days of first chemotherapy. After adjusting for missing
      data and guarantee-time bias, and using propensity score analysis to minimize
      indication bias, we compared overall survival of patients receiving adjuvant
      therapies with untreated case subjects. Results: Adjuvant chemotherapy was
      administered to 28.8% of 4775 patients, and upfront chemoradiation to 13.5%.
      Treatment was less frequent among patients who were older, patients with
      comorbidities, and among white Hispanic women. T3 or node-positive disease,
      microscopically positive margins, or extended resection increased the likelihood
      of adjuvant therapy. Overall survival at three years was 39.9% (95% confidence
      interval [CI] = 38.4% to 41.4%) and was unaffected by adjuvant therapy after
      adjusting for multiple confounders (hazard ratio = 1.01, 95% CI = 0.92 to 1.10).
      Patients with T3 or node-positive tumors treated with upfront adjuvant
      chemoradiation had a modest early survival advantage (absolute difference at two
      years = 6.8%, 95% CI = 1.1% to 12.6%), but survival curves converged after five
      years of follow-up. Conclusions: The curative potential of current adjuvant
      therapy in gallbladder cancer is questionable, justifying placebo-controlled
      investigation of novel chemotherapy combinations or alternative approaches.
      Chemoradiation may provide a short-term benefit in locally advanced tumors.

PMID- 27707845
TI  - The Objective Measurement of Brace-Use Adherence in the Treatment of Idiopathic
      Clubfoot.
AB  - BACKGROUND: A successful outcome for the treatment of idiopathic clubfoot is
      believed to require adequate adherence to brace use. Previous studies have relied
      on parental reporting of brace application. We used temperature sensors to
      determine the adherence to the bracing protocol, the accuracy of parent-reported
      use, and differences in adherence between patients who experienced relapse of
      deformity and those who did not. METHODS: Using wireless sensors attached to
      brace sandals, we monitored brace wear over a 3-month period in this cross
      sectional study involving 48 patients in 4 age-based groups: 6 to 12 months
      (Group 1), >1 to 2 years (Group 2), >2 to 3 years (Group 3), and >3 to 4 years
      (Group 4). Parents were blinded to the purpose of the sensors. The mean number of
      hours of daily brace use as measured by the sensors was compared with the
      physician-recommended hours and parent-reported hours of brace use. RESULTS:
      Sensors were retrieved from 44 of 48 patients. Overall, the median brace use
      recorded by the sensors was 62% (range, 5% to 125%) of that recommended by the
      physician, and 77% (range, 6% to 213%) of that reported by the parents. For
      Groups 1 to 3, the difference between the physician-recommended and measured
      number of hours of daily brace use was significant (p <= 0.002), and the
      difference between the parent-reported and measured number of hours of daily
      brace use was also significant (p <= 0.013). Eight (18%) of the 44 patients who
      completed the study experienced relapse during the period of monitoring; most
      importantly, the mean number of hours of brace wear for these patients, 5 hours
      per day (median, 4; and standard deviation [SD], 3 hours per day) was
      significantly lower than the 8 hours per day for those who did not experience
      relapse (median, 9; and SD, 5 hours per day) (p = 0.045). CONCLUSIONS: The
      present study objectively quantified the number of daily hours of post-corrective
      brace wear for patients with clubfoot in varying age groups and provides an
      estimate of the number of hours required to avoid relapse. LEVEL OF EVIDENCE:
      Therapeutic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 27707846
TI  - Radiographic Changes in the Cervical Spine Following Anterior Arthrodesis: A Long
      Term Analysis of 166 Patients.
AB  - BACKGROUND: Adjacent segment degeneration frequently develops following anterior
      cervical discectomy and fusion. The objectives of the present study were to
      characterize the long-term evolution of degenerative radiographic changes at
      segments adjacent to anterior cervical fusion and to identify factors associated
      with the development of these changes, including the preoperative condition of
      the cervical spine and parameters related to arthrodeses. METHODS: One hundred
      and sixty-six patients who underwent anterior cervical discectomy and fusion for
      symptomatic cervical spondylosis or disc herniation were followed
      radiographically for a mean time of 12.7 years (range, 5 to 30 years).
      Radiographic changes representing degeneration at adjacent levels, including disc
      height loss, osteophyte formation, end-plate sclerosis, and facet arthrosis,
      along with changes in sagittal alignment of the fusion segment and cervical
      spine, were recorded preoperatively and at the time of the latest follow-up.
      Regression models were used to identify the parameters that affect these
      degenerative changes. RESULTS: More than 90% of patients had worsened anterior
      and posterior osteophytes at segments immediately adjacent to the fusion.
      Degenerative changes were significantly affected by the proximity of the level to
      the fusion and were inversely affected by the preoperative degenerative changes
      present at the segment (p < 0.0001). The time elapsed since the surgical
      procedure was a significant predictor of degenerative changes (p < 0.0001).
      However, the patient age, the number of levels fused, and the sagittal alignment
      of the fusion segment had no influence on the degenerative changes at adjacent
      segments. CONCLUSIONS: Multiple factors likely contribute to adjacent segment
      degeneration following cervical arthrodesis. Although mechanical parameters
      associated with arthrodesis, such as length and alignment of the fusion, did not
      appear to play a role, the preoperative degenerative condition of the spine and
      inclusion of C5-C6 in the arthrodesis influenced the incidence of adjacent
      segment degeneration. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 27707847
TI  - Cardiopulmonary Exercise Testing in Patients with Idiopathic Scoliosis.
AB  - BACKGROUND: Scoliosis causes impairment of the respiratory and cardiovascular
      systems. Traditional pulmonary function tests only examine patients under static
      conditions. The aim of our study was to investigate the correlation between
      radiographic parameters and dynamic cardiopulmonary capacity in patients with
      idiopathic scoliosis. METHODS: Forty patients with idiopathic scoliosis were
      included in this prospective study from January 2014 to February 2016. The
      patients underwent full radiographic assessment of deformity, pulmonary function
      testing, and cardiopulmonary bicycle ergometer testing. The impact of the
      severity of thoracic curvature and kyphosis on pulmonary function and physical
      capacity was investigated. RESULTS: Thirty-three female patients with a mean age
      of 15.5 years (range, 11 to 35 years) and coronal thoracic curvature of 49.4
      degrees  (range, 24 degrees  to 76 degrees ) and 7 male subjects with a mean age
      of 15.9 years (range, 13 to 18 years) and coronal thoracic curvature of 47.1
      degrees (range, 22 degrees  to 80 degrees ) were included. No correlation was
      found between coronal thoracic curvature and pulmonary function test results in
      the female patients. Female patients with a thoracic curve of >=60 degrees  had
      lower blood oxygen saturation at maximal exercise in the cardiopulmonary exercise
      test (p = 0.032). Female patients with a thoracic curve of >=50 degrees  had a
      higher respiratory rate (p = 0.041) and ventilation volume per minute (p = 0.046)
      and lower breathing reserve at maximal exercise (p = 0.038). Thoracic kyphosis in
      female patients was positively correlated with pulmonary function, as shown by
      the forced expiratory volume in 1 second (r = 0.456, p = 0.01), forced vital
      capacity (r = 0.366, p = 0.043), vital capacity (r = 0.525, p = 0.006), and total
      lung capacity (r = 0.388, p = 0.031), as well as with tidal volume (r = 0.401, p
      = 0.025) in cardiopulmonary exercise testing. Female patients who engaged in
      regular exercise had better peak oxygen intake normalized by body weight (p <
      0.001), peak oxygen intake normalized by the predicted value (p = 0.003), maximum
      heart rate (p = 0.020), and heart rate reserve (p = 0.014). CONCLUSIONS: Overall
      exercise tolerance was not correlated with the magnitude of the thoracic curve
      and kyphosis. Some parameters of ventilatory function and pulmonary gas exchange
      worsened as thoracic curvature increased or kyphosis decreased. Exercise capacity
      was better in patients who engaged in regular aerobic exercise, and physical
      activity is recommended for patients with idiopathic scoliosis. LEVEL OF
      EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 27707848
TI  - Functional Outcomes After Operative Management of Extra-Articular Glenoid Neck
      and Scapular Body Fractures.
AB  - BACKGROUND: This study's purpose was to assess patient-based functional outcomes
      following open reduction and internal fixation (ORIF) of displaced scapular body
      and glenoid neck fractures. This series represents a 9-year experience at a level
      I trauma center and referral destination for this injury. METHODS: A database was
      established to record surgical and functional outcomes of scapular fractures
      treated with ORIF. For this report, the cases of all patients who had a glenoid
      neck or scapular body fracture (AO/OTA 14-A3 or 14-C1) without intra-articular
      involvement were reviewed. Operative indications included medial/lateral
      displacement of >=20 mm, angulation of >=45 degrees , medial/lateral displacement
      of >=15 mm with angulation of >=30 degrees , double disruptions of the superior
      shoulder suspensory complex with both displaced >=10 mm, a glenopolar angle of
      <=22 degrees , and an open fracture. The results of clinical testing, including
      measurements of range of motion and strength and scores on the Disabilities of
      the Arm, Shoulder and Hand (DASH) and Short Form-36 (SF-36) questionnaires, were
      recorded at each follow-up appointment. RESULTS: Between 2002 and 2011, 61
      patients with an extra-articular scapular fracture were treated surgically within
      20 days after the injury; 19 patients (31%) had >=2 operative indications. Of the
      61 patients, 49 (80%) were followed for >=1 year (mean, 33 months; range, 12 to
      138 months) following surgery. There was a 100% union rate at the time of final
      follow-up, with a mean DASH score of 12.1 points (range, 0 to 54 points). For all
      parameters, the mean SF-36 scores of the study patients were comparable with
      normative population scores. The range of motion of the operatively treated and
      contralateral shoulders averaged, respectively, 154 degrees  and 159 degrees  of
      forward flexion, 106 degrees  and 108 degrees  of abduction, and 66 degrees  and
      70 degrees  of external rotation. The strength of the operatively treated and
      contralateral shoulders averaged, respectively, 20 and 23 lb (89.0 and 102.3 N)
      of force in forward flexion, 14 and 16 lb (62.3 and 71.2 N) in abduction, and 19
      and 23 lb (84.5 and 102.3 N) in external rotation. Complications and/or secondary
      surgery were recorded for 8 patients (16%). CONCLUSIONS: Displaced scapular body
      and glenoid neck fractures that meet current published standards for ORIF can be
      treated operatively with predictably good functional outcomes. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 27707849
TI  - Outcome of Revision Shoulder Arthroplasty After Resurfacing Hemiarthroplasty in
      Patients with Glenohumeral Osteoarthritis.
AB  - BACKGROUND: Patients are often treated with a resurfacing hemiarthroplasty in the
      expectation that the bone-preserving design facilitates revision should the need
      for a revision arthroplasty arise. The aim of this study was to report the
      outcome of patients with glenohumeral osteoarthritis who underwent revision
      shoulder arthroplasty after resurfacing hemiarthroplasty. METHODS: We reviewed
      all patients with osteoarthritis reported to the Danish Shoulder Arthroplasty
      Registry from 2006 to 2013. There were 1,210 primary resurfacing
      hemiarthroplasties, of which 107 cases (9%) required a revision surgical
      procedure, defined as the removal or exchange of the humeral component or the
      addition of a glenoid component. The Western Ontario Osteoarthritis of the
      Shoulder (WOOS) index was used to evaluate outcome at 1 year. RESULTS: The median
      WOOS of revision arthroplasty after failed resurfacing hemiarthroplasty was 62
      points (interquartile range, 40 to 88 points). Of the 80 cases that had follow
      up, 33 (41%) had an unacceptable outcome, defined as a WOOS of <=50 points. Of
      the 107 cases that required a revision surgical procedure, 11 arthroplasties
      (10%) required a further revision surgical procedure. The resurfacing
      hemiarthroplasty was revised to a stemmed hemiarthroplasty (n = 39), anatomic
      total shoulder arthroplasty (n = 31), or reverse shoulder arthroplasty (n = 30).
      In 7 cases, the revision arthroplasty design was unknown. The median WOOS of
      patients who underwent revision stemmed hemiarthroplasty (48 points) was
      significantly inferior (p = 0.002) to that of patients who underwent primary
      stemmed hemiarthroplasty (75 points); the median WOOS of patients who underwent
      revision anatomic total shoulder arthroplasty (74 points) was also significantly
      inferior (p = 0.007) to that of patients who underwent primary anatomic total
      shoulder arthroplasty (93 points). However, the median WOOS of patients who
      underwent revision reverse shoulder arthroplasty (68 points) was not
      significantly different (p = 0.66) from that of patients who underwent primary
      reverse shoulder arthroplasty (77 points) used in the treatment of
      osteoarthritis. CONCLUSIONS: The outcome of revision shoulder arthroplasty after
      failed resurfacing hemiarthroplasty was variable and, in many cases,
      disappointing. It is important that resurfacing hemiarthroplasty is used for the
      correct indications and with adequate technique and skill. When resurfacing
      hemiarthroplasty is used in the treatment of osteoarthritis, revision cannot be
      counted upon as a fallback. LEVEL OF EVIDENCE: Therapeutic Level II. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 27707850
TI  - The Accuracy of Imaging Techniques in the Assessment of Periprosthetic Hip
      Infection: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Various imaging techniques are used for excluding or confirming
      periprosthetic hip infection, but there is no consensus regarding the most
      accurate technique. The objective of this study was to determine the accuracy of
      current imaging modalities in diagnosing periprosthetic hip infection. METHODS: A
      systematic review and meta-analysis of the literature was conducted with a
      comprehensive search of MEDLINE and Embase to identify clinical studies in which
      periprosthetic hip infection was investigated with different imaging modalities.
      The sensitivity and specificity of each imaging technique were determined and
      compared with the results of microbiological and histological analysis,
      intraoperative findings, and clinical follow-up of >6 months. RESULTS: A total of
      31 studies, published between 1988 and 2014, were included for meta-analysis,
      representing 1,753 hip prostheses. Quality assessment of the included studies
      identified low concerns with regard to external validity but more concerns with
      regard to internal validity including risk of bias (>50% of studies had
      insufficient information). No meta-analysis was performed for radiography,
      ultrasonography, computed tomography, and magnetic resonance imaging because of
      insufficient available clinical data. The pooled sensitivity and specificity were
      88% (95% confidence interval [CI], 81% to 94%) and 92% (95% CI, 88% to 96%),
      respectively, for leukocyte scintigraphy; 86% (95% CI, 80% to 90%) and 93% (95%
      CI, 90% to 95%) for fluorodeoxyglucose positron emission tomography (FDG PET);
      69% (95% CI, 58% to 79%) and 96% (95% CI, 93% to 98%) for combined leukocyte and
      bone marrow scintigraphy; 84% (95% CI, 70% to 93%) and 75% (95% CI, 66% to 82%)
      for antigranulocyte scintigraphy; and 80% (95% CI, 72% to 86%) and 69% (95% CI,
      64% to 73%) for bone scintigraphy. CONCLUSIONS: Of the currently used imaging
      techniques, leukocyte scintigraphy has satisfactory accuracy in confirming or
      excluding periprosthetic hip infection. Although not significantly different,
      combined leukocyte and bone marrow scintigraphy was the most specific imaging
      technique. FDG PET has an appropriate accuracy in confirming or excluding
      periprosthetic hip infection, but may not yet be the preferred imaging modality
      because of limited availability and relatively higher cost. LEVEL OF EVIDENCE:
      Diagnostic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 27707852
TI  - Microstructural and Mechanical Properties of the Posterior Cruciate Ligament: A
      Comparison of the Anterolateral and Posteromedial Bundles.
AB  - BACKGROUND: The microstructural organization (collagen fiber alignment) of the
      posterior cruciate ligament (PCL), which likely corresponds with its functional
      properties, has only been described qualitatively in the literature, to our
      knowledge. The goal of this study was to quantify the tensile mechanical and
      microstructural properties of the PCL and compare these qualities between the
      anterolateral and posteromedial bundles. METHODS: Twenty-two knee specimens from
      13 donors (8 male and 5 female; mean age [and standard deviation] at the time of
      death, 43.0 +/- 4.1 years; mean body mass index, 30.0 +/- 6.7 kg/m2) were
      dissected to isolate the PCL, and each bundle was split into 3 regions.
      Mechanical testing of each regional sample consisted of preconditioning followed
      by a ramp-and-hold stress-relaxation test and a quasi-static ramp-to-failure
      test. Microstructural analysis was performed with use of a high-resolution,
      division-of-focal-plane polarization camera to evaluate the average direction of
      collagen orientation and the degree to which the collagen fibers were aligned in
      that direction. Results were compared between the anterolateral and posteromedial
      bundles and across the regions of each bundle. RESULTS: The anterolateral and
      posteromedial bundles demonstrated largely equivalent mechanical and
      microstructural properties. Elastic moduli in the toe and linear regions were not
      different; however, the posteromedial bundle did show significantly more stress
      relaxation (p = 0.004). There were also few differences in microstructural
      properties between bundles, which again were seen only in stress relaxation.
      Comparing regions within each bundle, several mechanical and microstructural
      parameters showed significant relationships across the posteromedial bundle,
      following a gradient of decreasing strength and alignment from anterior to
      posterior. CONCLUSIONS: The PCL has relatively homogenous microstructural and
      mechanical properties, with few differences between the anterolateral and
      posteromedial bundles. This finding suggests that distinct functions of the PCL
      bundles result primarily from size and anatomical location rather than from
      differences in these properties. CLINICAL RELEVANCE: These properties of the PCL
      can be used to assess the utility of graft choices and operative techniques for
      PCL reconstruction and may partly explain limited differences in the outcomes of
      single-bundle compared with double-bundle reconstruction techniques for the PCL.

PMID- 27707851
TI  - The Michigan Experience with Safety and Effectiveness of Tranexamic Acid Use in
      Hip and Knee Arthroplasty.
AB  - BACKGROUND: The efficacy of tranexamic acid (TXA) in reducing blood loss and
      transfusion requirements in total hip and knee arthroplasty has been well
      established in small controlled clinical trials and meta-analyses. The purpose of
      the current study was to determine the risks and benefits of TXA use in routine
      orthopaedic surgical practice on the basis of data from a large, statewide
      arthroplasty registry. METHODS: From April 18, 2013, to September 30, 2014, there
      were 23,236 primary total knee arthroplasty cases and 11,489 primary total hip
      arthroplasty cases completed and registered in the Michigan Arthroplasty Registry
      Collaborative Quality Initiative (MARCQI). We evaluated the association between
      TXA use and hemoglobin drop, transfusion, length of stay (LOS), venous
      thromboembolism (VTE), readmission, and cardiovascular events by fitting mixed
      effects generalized linear and mixed-effects Cox models. We used inverse
      probability of treatment weighting to enhance causal inference. RESULTS: For
      total hip arthroplasty, TXA use was associated with a smaller drop in hemoglobin
      (mean difference = -0.65 g/dL; 95% confidence interval [CI] = -0.60 to -0.71
      g/dL), decreased odds of blood transfusion (odds ratio [OR] = 0.72; 95% CI = 0.60
      to 0.86), and decreased readmissions (OR = 0.77; 95% CI = 0.64 to 0.93) compared
      with no TXA use. There was no effect on VTE (hazard ratio [HR] = 0.91; 95% CI =
      0.62 to 1.33), LOS (incident rate ratio [IRR] = 1.00; 95% CI = 0.97 to 1.03), or
      cardiovascular events (OR = 0.85; 95% CI = 0.47 to 1.52). For total knee
      arthroplasty, TXA was associated with a smaller drop in hemoglobin (mean
      difference = -0.68 g/dL; 95% CI = -0.64 to -0.71 g/dL) and one-fourth the odds of
      blood transfusion (OR = 0.26; 95% CI = 0.21 to 0.31). There was an association
      with decreased risk of VTE within 90 days after surgery (HR = 0.56; 95% CI = 0.42
      to 0.73), slightly decreased LOS (IRR = 0.93; 95% CI = 0.92 to 0.95), and no
      association with readmissions (OR = 0.90; 95% CI = 0.79 to 1.04) or
      cardiovascular events (OR = 1.12; 95% CI = 0.74 to 1.71). CONCLUSIONS: In routine
      orthopaedic surgery practice, TXA use was associated with decreased blood loss
      and transfusion risk for both total knee and total hip arthroplasty, without
      evidence of increased risk of complications. TXA use was also associated with
      reduced risk of readmission among total hip arthroplasty patients and reduced
      risk of VTE among total knee arthroplasty patients, and did not have an adverse
      effect on cardiovascular complications in either group. LEVEL OF EVIDENCE:
      Therapeutic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 27707853
TI  - Developing a Clinically Representative Model of Periprosthetic Joint Infection.
AB  - ?The poor treatment outcomes for periprosthetic joint infection (PJI) reflect the
      limited understanding that currently exists regarding the pathogenesis of this
      devastating clinical problem.?Current animal models of PJI are limited in their
      translational nature primarily because of their inability to recreate the
      periprosthetic environment.?A greater mechanistic understanding of the
      musculoskeletal and immune systems of small animals, such as mice and rats,
      provides a more robust platform for modeling and examining the pathogenesis of
      PJI.?A clinically representative PJI model must involve an implant that recreates
      the periprosthetic space and be amenable to methodologies that identify implant
      biofilm as well as quantify the peri-implant bacterial load.

PMID- 27707854
TI  - What's Important: The Unhappy Patient.

PMID- 27707855
TI  - The Age of OrthoInfo: A Randomized Controlled Trial Evaluating Patient
      Comprehension of Informed Consent.
AB  - BACKGROUND: Integral to an orthopaedic surgeon-patient informed consent
      discussion is the assessment of patient comprehension of their medical care.
      However, little is known about how to optimize patient comprehension of an
      informed consent discussion. The purpose of our study was to evaluate three time
      controlled informed consent discussion methods to determine which optimized
      patient comprehension immediately after the discussion. METHODS: Sixty-seven
      consecutive patients with knee osteoarthritis who were considered medically
      appropriate for a knee corticosteroid injection were enrolled in our trial.
      Participants were randomized and were allocated into one of three groups in a
      parallel fashion and 1:1:1 ratio. Our three groups varied by sensory input and
      included verbal (hearing), verbal and video (hearing and sight), and verbal and
      model (hearing, sight, and touch). Each participant listened to a 10-minute
      scripted lecture given by a researcher; this lecture was based on content from
      the American Academy of Orthopaedic Surgeons patient education web site
      OrthoInfo. Patient comprehension was assessed after the lecture using a validated
      questionnaire called the Nkem test. Our primary outcome evaluated patient
      comprehension utilizing a pairwise comparison of mean comprehension scores
      between the groups. The primary outcome was analyzed using a one-way analysis of
      variance with the least significant difference calculated post hoc and a 95%
      confidence interval (95% CI). The health-care staff, study participants, and
      outcome assessor were each blinded to group assignments. RESULTS: The mean
      comprehension scores were 84% (95% CI, 79% to 88%) for the verbal and model
      group, 74% (95% CI, 63% to 80%) for the verbal and video group, and 71% (95% CI,
      61% to 80%) for the verbal group. The omnibus analysis of variance was
      significant and showed a difference among the groups (p = 0.019). The pairwise
      comparison of the groups using the least significant difference calculated post
      hoc showed that the verbal and model group outperformed the verbal group (p =
      0.01) and the verbal and video group (p = 0.023). CONCLUSIONS: Multisensory
      patient education incorporating OrthoInfo and an anatomic model optimized patient
      comprehension immediately after a time-controlled informed consent discussion.
      This finding could play an important role in improving surgeon-patient
      communication in the field of orthopaedic surgery.

PMID- 27707856
TI  - The Early Impact of an Administrative Processing Fee on Manuscript Submissions at
      The Journal of Bone & Joint Surgery.
AB  - BACKGROUND: There was a dramatic increase in the volume of manuscripts submitted
      to The Journal of Bone & Joint Surgery (JBJS) between 2009 and 2012. This
      resulted in increased journal administrative costs. To offset this financial
      burden, in May 2013, JBJS started charging authors an administrative processing
      fee at the time of submission. The purpose of this study was to assess the impact
      of the administrative fee on the volume and characteristics of manuscripts
      submitted to JBJS. METHODS: Our analysis included 866 manuscripts submitted to
      JBJS between November 2012 and November 2013. We compared manuscripts submitted 6
      months prior to fee implementation and prior to the announcement (denoted as the
      baseline group), in the several months prior to fee implementation but after the
      fee implementation announcement (denoted as the fee announcement group), and in
      the 6 months after fee implementation (denoted as the fee implementation group).
      Manuscripts were reviewed for institutional and author demographic
      characteristics, as well as for general study characteristics. RESULTS: In the
      first full calendar year (2014) after the implementation of the fee, the annual
      volume of submissions to JBJS declined by 33.5% compared with the annual
      submission volume in 2010 to 2012. In a comparative analysis, the geographical
      region of origin (p = 0.003), level of evidence (p < 0.0001), funding, and
      specialty differed between the 3 submission periods. However, subgroup analyses
      demonstrated that differences were attributable to the fee announcement group and
      that there were few important differences between the baseline and fee
      implementation groups. Reporting of funding information improved significantly
      between the baseline and fee implementation groups; in the post-fee
      implementation period, studies were more likely to have declared no external
      funding source (p = 0.001). CONCLUSIONS: The administrative processing fee at
      JBJS has been associated with a decrease in submission volume, but, overall,
      there has not been a change in the characteristics of studies submitted. However,
      decreased overall volume implies a decrease in the absolute number of high-level
      studies submitted to the journal. Administrative processing fees at high-volume
      journals may be a financially viable way to offset high administrative costs
      without substantially changing the characteristics of submitted articles.

PMID- 27707857
TI  - Measuring Quality of Care with Patient Satisfaction Scores.
AB  - Quality of care is a multidimensional concept encompassing safety, efficiency,
      outcomes, and the patient experience. Traditional quality metrics, such as
      mortality rates, complication rates, and patient-reported outcomes, are time
      consuming and cost-consuming to obtain and risk-stratify. The implications of
      reimbursement related to patient satisfaction and the ease of data collection
      have contributed to the perception that satisfaction is a global indicator of
      health-care quality; however, high satisfaction scores are not consistently
      correlated with traditional outcome and safety indicators. Higher patient
      satisfaction may be associated with increased costs of care. Costs may be further
      increased by the implementation of the satisfaction surveys themselves, which can
      increase imaging studies and prescriptions. Therefore, satisfaction surveys are
      not appropriate measures of overall quality of care. Accurate assessment of
      quality requires a multidimensional approach that includes specific measures for
      each domain.

PMID- 27707858
TI  - Post-Interview Communication During Application to Orthopaedic Surgery Residency
      Programs.
AB  - BACKGROUND: Post-interview communication from residency programs to applicants is
      common during the U.S. residency match process. The goals of this study were to
      understand the frequency and type of post-interview communication, how this
      communication influences applicants' ranking of programs, whether programs use
      "second-look" visits to gauge or to encourage applicant interest, and the
      financial costs to applicants of second-look visits. METHODS: A post-match survey
      was sent to 1,198 applicants to one academic orthopaedic residency program over 2
      years. The response rates were 15% in 2014 and 31% in 2015, totaling 293
      responses used for analysis. RESULTS: Sixty-four percent of applicants reported
      having post-interview communication with one or more programs. Seventeen percent
      said that communication caused them to rank the contacting program higher or to
      keep the program ranked as number 1. Twenty percent felt pressured to reveal
      their rank position, and 8% were asked to rank a program first in exchange for
      the program's promise to rank the applicant first. Applicants who received post
      interview communication had odds that were 13.5 times higher (95% confidence
      interval, 6.2 to 30 times higher) of matching to the programs that contacted
      them. Ninety percent of applicants said that communication from a program did not
      change how they ranked the program with which they eventually matched. Seventeen
      percent were encouraged to attend second-look visits, incurring a mean cost of
      $600 (range, $20 to $8,000). CONCLUSIONS: Orthopaedic residency programs continue
      to communicate with applicants in ways that violate the National Resident
      Matching Program's Match Communication Code of Conduct, and they continue to
      encourage second-look visits. To improve the integrity of the match, we suggest
      that programs use no-reply e-mails to minimize influence and pressure on
      applicants, interviewers and applicants review the Code of Conduct on interview
      day and provide instructions on reporting violations to the National Resident
      Matching Program, all post-interview communication be directed to a standardized
      or neutral third party, and programs actively discourage second-look visits and
      stop requiring second-look visits.

PMID- 27707859
TI  - Radiographic Changes in the Cervical Spine Following Arthrodesis: Causation or
      Correlation? Commentary on an article by Raj D. Rao, MD, et al.: "Radiographic
      Changes in the Cervical Spine Following Anterior Arthrodesis: A Long-Term
      Analysis of 166 Patients".

PMID- 27707860
TI  - Making Tranexamic Acid the Standard of Care in Hip and Knee Arthroplasty:
      Commentary on an article by Brian Hallstrom, MD, et al.: "The Michigan Experience
      with Safety and Effectiveness of Tranexamic Acid Use in Hip and Knee
      Arthroplasty".

PMID- 27707861
TI  - Erratum.

PMID- 27707863
TI  - Wolbachia increases the susceptibility of a parasitoid wasp to hyperparasitism.
AB  - The success of maternally transmitted endosymbiotic bacteria, such as Wolbachia,
      is directly linked to their host reproduction but in direct conflict with other
      parasites that kill the host before it reaches reproductive maturity. Therefore,
      symbionts that have evolved strategies to increase their host's ability to evade
      lethal parasites may have high penetrance, while detrimental symbionts would be
      selected against, leading to lower penetrance or extinction from the host
      population. In a natural population of the parasitoid wasp Hyposoter horticola in
      the Aland Islands (Finland), the Wolbachia strain wHho persists at an
      intermediate prevalence (~50%). Additionally, there is a negative correlation
      between the prevalence of Wolbachia and a hyperparasitoid wasp, Mesochorus cf.
      stigmaticus, in the landscape. Using a manipulative field experiment, we
      addressed the persistence of Wolbachia at this intermediate level, and tested
      whether the observed negative correlation could be due to Wolbachia inducing
      either susceptibility or resistance to parasitism. We show that infection with
      Wolbachia does not influence the ability of the wasp to parasitize its butterfly
      host, Melitaea cinxia, but that hyperparasitism of the wasp increases in the
      presence of wHho. Consequently, the symbiont is detrimental, and in order to
      persist in the host population, must also have a positive effect on fitness that
      outweighs the costly burden of susceptibility to widespread parasitism.

PMID- 27707862
TI  - Understanding how animal groups achieve coordinated movement.
AB  - Moving animal groups display remarkable feats of coordination. This coordination
      is largely achieved when individuals adjust their movement in response to their
      neighbours' movements and positions. Recent advancements in automated tracking
      technologies, including computer vision and GPS, now allow researchers to gather
      large amounts of data on the movements and positions of individuals in groups.
      Furthermore, analytical techniques from fields such as statistical physics now
      allow us to identify the precise interaction rules used by animals on the move.
      These interaction rules differ not only between species, but also between
      individuals in the same group. These differences have wide-ranging implications,
      affecting how groups make collective decisions and driving the evolution of
      collective motion. Here, I describe how trajectory data can be used to infer how
      animals interact in moving groups. I give examples of the similarities and
      differences in the spatial and directional organisations of animal groups between
      species, and discuss the rules that animals use to achieve this organisation. I
      then explore how groups of the same species can exhibit different structures, and
      ask whether this results from individuals adapting their interaction rules. I
      then examine how the interaction rules between individuals in the same groups can
      also differ, and discuss how this can affect ecological and evolutionary
      processes. Finally, I suggest areas of future research.

PMID- 27707865
TI  - Testosterone activates sexual dimorphism including male-typical carotenoid but
      not melanin plumage pigmentation in a female bird.
AB  - In males it is frequently testosterone (T) that activates the expression of
      sexually selected morphological and behavioral displays, but the role of T in
      regulating similar traits in females is less clear. Here, we combine
      correlational data with results from T and gonadotropin-releasing hormone (GnRH)
      manipulations in both sexes to assess the role of T in mediating sexually
      dimorphic coloration and morphology in the red-backed fairy-wren (Malurus
      melanocephalus). We show that: (1) natural variation in female expression of
      ornamental traits (darkened bills and red back feathers) is positively associated
      with age and circulating androgen titres, (2) females have the capacity to
      express most male-typical traits in response to exogenous T, including carotenoid
      pigmented body plumage, shorter feathers, darkened bill and enlarged cloacal
      protuberance, but (3) appear constrained in production of male-typical melanin
      pigmented plumage, and (4) low androgen levels during the pre-nuptial molt,
      probably because of low ovarian capacity for steroid production (or luteinizing
      hormone sensitivity), prevent females from developing male-like ornamentation.
      Thus, females appear to retain molecular mechanisms for hormonally regulated male
      typical ornamentation, although these are rarely activated because of
      insufficient production of the hormonal signal.

PMID- 27707864
TI  - Voltage-gated calcium channels of Paramecium cilia.
AB  - Paramecium cells swim by beating their cilia, and make turns by transiently
      reversing their power stroke. Reversal is caused by Ca2+ entering the cilium
      through voltage-gated Ca2+ (CaV) channels that are found exclusively in the
      cilia. As ciliary Ca2+ levels return to normal, the cell pivots and swims forward
      in a new direction. Thus, the activation of the CaV channels causes cells to make
      a turn in their swimming paths. For 45 years, the physiological characteristics
      of the Paramecium ciliary CaV channels have been known, but the proteins were not
      identified until recently, when the P. tetraurelia ciliary membrane proteome was
      determined. Three CaValpha1 subunits that were identified among the proteins were
      cloned and confirmed to be expressed in the cilia. We demonstrate using RNA
      interference that these channels function as the ciliary CaV channels that are
      responsible for the reversal of ciliary beating. Furthermore, we show that Pawn
      (pw) mutants of Paramecium that cannot swim backward for lack of CaV channel
      activity do not express any of the three CaV1 channels in their ciliary membrane,
      until they are rescued from the mutant phenotype by expression of the wild-type
      PW gene. These results reinforce the correlation of the three CaV channels with
      backward swimming through ciliary reversal. The PwB protein, found in endoplasmic
      reticulum fractions, co-immunoprecipitates with the CaV1c channel and perhaps
      functions in trafficking. The PwA protein does not appear to have an interaction
      with the channel proteins but affects their appearance in the cilia.

PMID- 27707866
TI  - Metabolic recovery from drowning by insect pupae.
AB  - Many terrestrial insects live in environments that flood intermittently, and some
      life stages may spend days underwater without access to oxygen. We tested the
      hypothesis that terrestrial insects with underground pupae show respiratory
      adaptations for surviving anoxia and subsequently reestablishing normal patterns
      of respiration. Pupae of Manduca sexta were experimentally immersed in water for
      between 0 and 13 days. All pupae survived up to 5 days of immersion regardless of
      whether the water was aerated or anoxic. By contrast, fifth-instar larvae
      survived a maximum of 4 h of immersion. There were no effects of immersion during
      the pupal period on adult size and morphology. After immersion, pupae initially
      emitted large pulses of CO2 After a subsequent trough in CO2 emission, spiracular
      activity resumed and average levels of CO2 emission were then elevated for
      approximately 1 day in the group immersed for 1 day and for at least 2 days in
      the 3- and 5-day immersion treatments. Although patterns of CO2 emission were
      diverse, most pupae went through a period during which they emitted CO2 in a
      cyclic pattern with periods of 0.78-2.2 min. These high-frequency cycles are not
      predicted by the recent models of Forster and Hetz (2010) and Grieshaber and
      Terblanche (2015), and we suggest several potential ways to reconcile the models
      with our observations. During immersion, pupae accumulated lactate, which then
      declined to low levels over 12-48 h. Pupae in the 3- and 5-day immersion groups
      still had elevated rates of CO2 emission after 48 h, suggesting that they
      continued to spend energy on reestablishing homeostasis even after lactate had
      returned to low levels. Despite their status as terrestrial insects, pupae of M.
      sexta can withstand long periods of immersion and anoxia and can reestablish
      homeostasis subsequently.

PMID- 27707867
TI  - The diversity and evolution of locomotor muscle properties in anurans.
AB  - Anuran jumping is a model system for linking muscle physiology to organismal
      performance. However, anuran species display substantial diversity in their
      locomotion, with some species performing powerful leaps from riverbanks or tree
      branches, while other species move predominantly via swimming, short hops or even
      diagonal-sequence gaits. Furthermore, many anurans with similar locomotion and
      morphology are actually convergent (e.g. multiple independent evolutions of 'tree
      frogs'), while closely related species may differ drastically, as with the
      walking toad (Melanophryniscus stelzneri) and bullfrog-like river toad
      (Phrynoides aspera) compared with other Bufonid toads. These multiple independent
      evolutionary changes in locomotion allow us to test the hypothesis that
      evolutionary increases in locomotor performance will be linked to the evolution
      of faster, high-power muscles. I tested the jumping, swimming and walking (when
      applicable) performance of 14 species of anurans and one salamander, followed by
      measurement of the contractile properties of the semimembranosus and plantaris
      longus muscles and anatomical measurements, using phylogenetic comparative
      methods. I found that increased jumping performance correlated to muscle
      contractile properties associated with muscle speed (e.g. time to peak tetanus,
      maximum shortening speed, peak isotonic power), and was tightly linked to
      relevant anatomical traits (e.g. leg length, muscle mass). Swimming performance
      was not correlated to jumping, and was correlated with fewer anatomical and
      muscular variables. Thus, muscle properties evolve along with changes in anatomy
      to produce differences in overall locomotor performance.

PMID- 27707870
TI  - Trends in epilepsy surgery: stable surgical numbers despite increasing
      presurgical volumes.
AB  - INTRODUCTION: Despite the success of epilepsy surgery, recent reports suggest a
      decline in surgical numbers. We tested these trends in our cohort to elucidate
      potential reasons. PATIENTS AND METHODS: Presurgical, surgical and postsurgical
      data of all patients undergoing presurgical evaluation in between 1990 and 2013
      were retrospectively analysed. Patients were grouped according to the underlying
      pathology. RESULTS: A total of 3060 patients were presurgically studied, and
      resective surgery was performed in 66.8% (n=2044) of them: medial temporal
      sclerosis (MTS): n=675, 33.0%; benign tumour (BT): n=408, 20.0%; and focal
      cortical dysplasia (FCD): n=284, 13.9%. Of these, 1929 patients (94.4%) had a
      follow-up of 2 years, and 50.8% were completely seizure free (Engel IA). Seizure
      freedom rate slightly improved over time. Presurgical evaluations continuously
      increased, whereas surgical interventions did not. Numbers for MTS, BT and
      temporal lobe resections decreased since 2009. The number of non-lesional
      patients and the need for intracranial recordings increased. More evaluated
      patients did not undergo surgery (more than 50% in 2010-2013) because patients
      were not suitable (mainly due to missing hypothesis: 4.5% in 1990-1993 up to
      21.1% in 2010-2013, total 13.4%) or declined from surgery (maximum 21.0% in 2010
      2013, total 10.9%). One potential reason may be that increasingly detailed
      information on chances and risks were given over time. CONCLUSIONS: The
      increasing volume of the presurgical programme largely compensates for decreasing
      numbers of surgically remediable syndromes and a growing rate of informed choice
      against epilepsy surgery. Although comprehensive diagnostic evaluation is offered
      to a larger group of epilepsy patients, surgical numbers remain stable.

PMID- 27707869
TI  - A work observation study of nuclear medicine technologists: interruptions,
      resilience and implications for patient safety.
AB  - BACKGROUND: Errors by nuclear medicine technologists during the preparation of
      radiopharmaceuticals or at other times can cause patient harm and may reflect the
      impact of interruptions, busy work environments and deficient systems or
      processes. We aimed to: (a) characterise the rate and nature of interruptions
      technologists experience and (b) identify strategies that support safety.
      METHODS: We performed 100 hours of observation of 11 technologists at a major
      public hospital and measured the proportions of time spent in eight categories of
      work tasks, location of task, interruption rate and type and multitasking (tasks
      conducted in parallel). We catalogued specific safety-oriented strategies used by
      technologists. RESULTS: Technologists completed 5227 tasks and experienced 569
      interruptions (mean, 4.5 times per hour; 95% CI 4.1 to 4.9). The highest
      interruption rate occurred when technologists were in transit between rooms (10.3
      per hour (95% CI 8.3 to 12.5)). Interruptions during radiopharmaceutical
      preparation occurred a mean of 4.4 times per hour (95% CI 3.3 to 5.6). Most
      (n=426) tasks were interrupted once only and all tasks were resumed after
      interruption. Multitasking occurred 16.6% of the time. At least some
      interruptions were initiated by other technologists to convey important
      information and/or to render assistance. Technologists employed a variety of
      verbal and non-verbal strategies in all work areas (notably in the hot-lab) to
      minimise the impact of interruptions and optimise the safe conduct of procedures.
      Although most were due to individual choices, some strategies reflected overt or
      subliminal departmental policy. CONCLUSIONS: Some interruptions appear
      beneficial. Technologists' self-initiated strategies to support safe work
      practices appear to be an important element in supporting a resilient work
      environment in nuclear medicine.

PMID- 27707871
TI  - Sclerotherapy for lymphatic malformations of the head and neck in the pediatric
      population.
AB  - BACKGROUND: Sclerotherapy is one of the most commonly used minimally invasive
      interventions in the treatment of macrocystic lymphatic malformations (LMs).
      Several different sclerosing agents and injection protocols have been reported in
      the literature, each with varying degrees of success. The safety and efficacy of
      the treatments have not been evaluated comparatively in the pediatric population.
      METHODS: Chart review of pediatric patients with macrocystic/mixed head and neck
      LMs who underwent sclerotherapy using OK-432, doxycycline, or ethanolamine oleate
      at Lucile Packard Children's Hospital at Stanford during 2000-2014. Clinical
      evaluation and radiographic imaging were reviewed to assess lesion
      characteristics and response to sclerotherapy following each treatment session.
      The post-intervention clinical response was categorized as excellent, good, fair,
      or poor. RESULTS: Among the 41 pediatric cases reviewed, 10 patients were treated
      with OK-432, 19 patients received doxycycline, and 12 patients received
      ethanolamine. In univariate analysis, different sclerosants had similar
      effectiveness after the first injection and final clinical outcome (p=0.5317). In
      multivariate analysis controlling for disease severity stage as well as disease
      characteristics (macrocystic vs mixed subtypes), different sclerosants also had
      similar effectiveness after the first injection (p=0.1192). Radiologic analysis
      indicated an 84.5% average volume reduction, with similar effectiveness between
      the different sclerosants (p=0.9910). CONCLUSIONS: In this series of LM cases
      treated at Stanford, we found that doxycycline, OK-432, and ethanolamine oleate
      sclerotherapy appear to have a similar safety and efficacy profile in the
      treatment of macrocystic and mixed LMs of the head and neck in the pediatric
      population.

PMID- 27707868
TI  - High-resolution metabolomics of occupational exposure to trichloroethylene.
AB  - BACKGROUND: Occupational exposure to trichloroethylene (TCE) has been linked to
      adverse health outcomes including non-Hodgkin's lymphoma and kidney and liver
      cancer; however, TCE's mode of action for development of these diseases in humans
      is not well understood. METHODS: Non-targeted metabolomics analysis of plasma
      obtained from 80 TCE-exposed workers [full shift exposure range of 0.4 to 230
      parts-per-million of air (ppma)] and 95 matched controls were completed by ultra
      high resolution mass spectrometry. Biological response to TCE exposure was
      determined using a metabolome-wide association study (MWAS) framework, with
      metabolic changes and plasma TCE metabolites evaluated by dose-response and
      pathway enrichment. Biological perturbations were then linked to immunological,
      renal and exposure molecular markers measured in the same population. RESULTS:
      Metabolic features associated with TCE exposure included known TCE metabolites,
      unidentifiable chlorinated compounds and endogenous metabolites. Exposure
      resulted in a systemic response in endogenous metabolism, including disruption in
      purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis
      pathways. Metabolite associations with TCE exposure included uric acid (beta =
      0.13, P-value = 3.6 * 10-5), glutamine (beta = 0.08, P-value = 0.0013), cystine
      (beta = 0.75, P-value = 0.0022), methylthioadenosine (beta = -1.6, P-value =
      0.0043), taurine (beta = -2.4, P-value = 0.0011) and chenodeoxycholic acid (beta
      = -1.3, P-value = 0.0039), which are consistent with known toxic effects of TCE,
      including immunosuppression, hepatotoxicity and nephrotoxicity. Correlation with
      additional exposure markers and physiological endpoints supported known disease
      associations. CONCLUSIONS: High-resolution metabolomics correlates measured
      occupational exposure to internal dose and metabolic response, providing insight
      into molecular mechanisms of exposure-related disease aetiology.

PMID- 27707872
TI  - In situ tissue engineering: endothelial growth patterns as a function of flow
      diverter design.
AB  - BACKGROUND: Vascular remodeling in response to implantation of a tissue
      engineering scaffold such as a flow diverter (FD) leads to the cure of
      intracranial aneurysms. We hypothesize that the vascular response is dependent on
      FD design, and CD34+ progenitor cells play an important role in the
      endothelialization of the implant. METHODS: Sixteen rabbit aneurysms were
      randomly treated with two different single-layer braided FDs made of cobalt
      chrome alloys. The FD-48 and FD-72 devices had 48 and 72 wires, respectively.
      Aneurysm occlusion rate was assessed during the final digital subtraction
      angiogram at 10, 20, 30, and 60 days (n=2 per device per time point). Implanted
      vessels were analyzed with scanning electron microscopy for tissue coverage,
      endothelialization, and immuno-gold labeling for CD34+ cells. RESULTS: Complete
      aneurysm occlusion rates were similar between the devices; however, complete or
      near complete occlusion was more frequently observed in aneurysms with neck <=4.2
      mm (p=0.008). Total tissue coverage at 10 days over the surface of the FD-48 and
      FD-72 devices was 56.4+/-11.6% and 76.6+/-3.6%, respectively. Endothelial cell
      growth over the surface was time-dependent for the FD-72 device (Spearman's
      r=0.86, p=0.013) but not for the FD-48 device (Spearman's r=-0.59, p=0.094). The
      endothelialization score was marginally correlated with the distance from the
      aneurysm neck for the FD-48 device (Spearman's r=1, p=0.083) but not for the FD
      72 device (Spearman's r=0.8, p=0.33). CD34+ cells were present along the entirety
      of both devices at all time points. CONCLUSIONS: This study gives preliminary
      evidence that temporal and spatial endothelialization is dependent on FD design.
      Circulating CD34+ progenitor cells contribute to endothelialization throughout
      the healing process.

PMID- 27707873
TI  - Prehospital care delivery and triage of stroke with emergent large vessel
      occlusion (ELVO): report of the Standards and Guidelines Committee of the Society
      of Neurointerventional Surgery.

PMID- 27707874
TI  - Endovascular isolation of intracranial blood blister-like aneurysms with Willis
      covered stent.
AB  - OBJECTIVE: Intracranial blood blister-like aneurysm (BBA) is a rare type of
      aneurysm that lacks all layers of the arterial wall. These fragile aneurysms have
      the propensity to rupture with minimal manipulation, which makes them hazardous
      and difficult to treat. The present study evaluated the safety and feasibility of
      endovascular treatment of BBAs with the Willis covered stent. MATERIALS: Thirteen
      patients (7 men and 6 women, age range 28-68 years) who presented with ruptured
      BBAs and were treated with the Willis covered stent were retrospectively
      reviewed. Results of the procedures and treatment-related complications were
      recorded. Angiographic and clinical follow-ups were performed 4-6 months after
      the procedure. RESULTS: Placement of the covered stent was successful in all
      patients. Immediate angiography showed complete aneurysm occlusion in 12 patients
      while one patient showed a mild endoleak. This high rate of aneurysm exclusion
      ensured the security of postoperative antiplatelet treatment. Occlusion of the
      ophthalmic artery occurred in two patients and occlusion of the anterior
      choroidal artery occurred in one patient; however, none of them showed acute or
      delayed clinical symptoms. Thrombosis, aneurysm rupture, and other complications
      did not develop in any case. Angiographic follow-up showed complete aneurysm
      exclusion without aneurysm recurrence in any patients. Only two patients showed
      asymptomatic mild to moderate in-stent stenosis. All patients had satisfactory
      clinical outcomes (modified Rankin Scale score <=1). CONCLUSIONS: Willis covered
      stent implementation may be safe and feasible for BBAs. This strategy might be a
      promising option for this high-risk type of aneurysm.

PMID- 27707875
TI  - Respect for autonomy: deciding what is good for oneself.
AB  - Paternalistic interference in autonomous decisions is typically impermissible.
      This has several explanations, among which is a view I call the agent
      constitution of the good: that the autonomous agent not only knows what is best
      for herself, but determines what is best for herself through her desires, goals
      and so on (her aims). For instance, it might seem that if an autonomous person
      does choose not to take insulin for her diabetes, then not only is it
      inappropriate to force treatment upon her, it is also not in her best interest to
      take insulin. Here I argue that agent-constitution, though appealing, is false.
      In fact, autonomous agents can be mistaken about their good, even when it seems
      to depend only upon their aims. Agent-constitution appears true only because we
      typically fail to notice constraints on a person's good in private, self
      regarding decisions where paternalism might be considered.

PMID- 27707876
TI  - Is it objectionable to create a child as a carer for a disabled parent?
AB  - In his recent paper, Adam Cureton presents a compelling case in support of the
      right of parents with disabilities to conceive and raise children. Cureton argues
      that (a) caring for a parent with a disability may be beneficial for a child and
      (b) the creation of a child with the intention of him/her being a carer for
      his/her disabled parent is objectionable. This response to Cureton's paper will
      focus on the creation of children with the purpose of them being carers for their
      disabled parents. I will respond to Cureton on three counts. First, I propose
      that claims (a) and (b) are incompatible. Second, I will argue that even from a
      Kantian perspective it is not clear that creating a child as a carer is
      objectionable. Third, I will argue more broadly that the intentions with which
      parents bring children into the world are not predictive of the concern parents
      should show their children once they come into existence.

PMID- 27707877
TI  - Which strings attached: ethical considerations for selecting appropriate
      conditionalities in conditional cash transfer programmes.
AB  - Conditional cash transfers (CCTs) present a promising approach to simultaneously
      tackle chronic poverty and poor health. While these programmes clearly embody
      beneficent aims, questions remain regarding the ethical design of CCTs. Limited
      guidance exists for the ethical evaluation of the defining feature of these
      programmes: the conditionalities. Drawing upon prominent public health ethics
      frameworks and social justice theories, this paper outlines five categories of
      morally relevant considerations that CCT programme designers should consider when
      assessing which behaviours or outcomes they select as conditionalities for
      payment: (1) likelihood of yielding desired health outcomes, (2) risks and
      burdens, (3) receptivity, (4) attainability and (5) indirect impacts and
      externalities. When evaluating potential conditionalities across these five
      categories of considerations, it is important to recognise that not all
      beneficiaries or subgroups of beneficiaries will fare equally on each. Given that
      most CCTs aim to reduce inequities and promote long-term health and prosperity
      for the most disadvantaged, it is critical to apply these considerations with due
      attention to how different segments of the beneficiary population will be
      differentially affected. Taken on balance, with due reflection on distributional
      effects, these five categories represent a comprehensive set of considerations
      for the moral analysis of specific conditionalities and will help ensure that CCT
      designers structure programmes in a way that is both morally sound and effective
      in achieving their goals.

PMID- 27707878
TI  - Incentives, equity and the Able Chooser Problem.
AB  - Health incentive schemes aim to produce healthier behaviours in target
      populations. They may do so both by making incentivised options more salient and
      by making them less costly. Changes in costs only result in healthier behaviour
      if the individual rationally assesses the cost change and acts accordingly. Not
      all people do this well. Those who fail to respond rationally to incentives will
      typically include those who are least able to make prudent choices more
      generally. This group will typically include the least advantaged more generally,
      since disadvantage inhibits one's effective ability to choose well and since poor
      choices tend to cause or aggravate disadvantage. Therefore, within the target
      population, health benefits to the better off may come at the cost of aggravated
      inequity. This is one instance of a problem I name the Able Chooser Problem,
      previously emphasised by Richard Arneson in relation to coercive paternalism. I
      describe and discuss this problem by distinguishing between policy options and
      their effects on the choice situation of individuals. Both positive and negative
      incentives, as well as mandates that are less than perfectly effective, require
      some sort of rational deliberation and action and so face the Able Chooser
      Problem. In contrast, effective restriction of what options are physically
      available, as well as choice context design that makes some options more salient
      or appealing, does not demand rational agency. These considerations provide an
      equity-based argument for preferring smart design of our choice and living
      environment to incentives and mandates.

PMID- 27707879
TI  - MAGI-1 Interacts with Nephrin to Maintain Slit Diaphragm Structure through
      Enhanced Rap1 Activation in Podocytes.
AB  - MAGI-1 is a multidomain cytosolic scaffolding protein that in the kidney is
      specifically located at the podocyte slit diaphragm, a specialized junction that
      is universally injured in proteinuric diseases. There it interacts with several
      essential molecules, including nephrin and neph1, which are required for slit
      diaphragm formation and as an intracellular signaling hub. Here, we show that
      diminished MAGI-1 expression in cultured podocytes reduced nephrin and neph1
      membrane localization and weakened tight junction integrity. Global magi1 knock
      out mice, however, demonstrated normal glomerular histology and function into
      adulthood. We hypothesized that a second mild but complementary genetic insult
      might induce glomerular disease susceptibility in these mice. To identify such a
      gene, we utilized the developing fly eye to test for functional complementation
      between MAGI and its binding partners. In this way, we identified diminished
      expression of fly Hibris (nephrin) or Roughest (neph1) as dramatically
      exacerbating the effects of MAGI depletion. Indeed, when these combinations were
      studied in mice, the addition of nephrin, but not neph1, heterozygosity to
      homozygous deletion of MAGI-1 resulted in spontaneous glomerulosclerosis. In
      cultured podocytes, MAGI-1 depletion reduced intercellular contact-induced Rap1
      activation, a pathway critical for proper podocyte function. Similarly, magi1
      knock-out mice showed diminished glomerular Rap1 activation, an effect
      dramatically enhanced by concomitant nephrin haploinsufficiency. Finally,
      combined overexpression of MAGI-1 and nephrin increased Rap1 activation, but not
      when substituting a mutant MAGI-1 that cannot bind nephrin. We conclude that the
      interaction between nephrin and MAGI-1 regulates Rap1 activation in podocytes to
      maintain long term slit diaphragm structure.

PMID- 27707881
TI  - Hero turned villain: NLRP3 inflammasome-induced inflammation during influenza A
      virus infection.
AB  - The severity of influenza A virus (IAV) infection can range from asymptotic to
      mild to severe. Infections, such as those seen following outbreaks of avian IAV,
      are associated with hyperinflammatory responses and the development of fatal
      disease. There is a continual threat that a novel or pandemic IAV will circulate
      in humans with high rates of mortality. The neuronal apoptosis inhibitor protein,
      class 2 transcription activator of the MHC, heterokaryon incompatibility,
      telomerase-associated protein 1, leucine-rich repeat, and pyrin domain-containing
      protein 3 (NLRP3) inflammasome is an innate immune sensor that has been shown to
      be critical for the secretion of the potent proinflammatory cytokines, IL-1beta
      and IL-18, as well as chemokine production and cellular inflammation in vivo
      following IAV infection. Initial studies illustrated a protective role of NLRP3
      during severe IAV infection in mice. However, the NLRP3 inflammasome may be a
      hero that turns villain in the later stages of severe IAV infection via the
      promotion of a hyperinflammatory state. Current treatments for patients who
      present to hospitals with a severe IAV infection are limited. The understanding
      of the mechanisms involved in the induction of NLRP3-dependent inflammation
      during severe IAV infections may provide new therapeutic targets that reduce
      human mortality.

PMID- 27707880
TI  - Pre-T Cell Receptors (Pre-TCRs) Leverage Vbeta Complementarity Determining
      Regions (CDRs) and Hydrophobic Patch in Mechanosensing Thymic Self-ligands.
AB  - The pre-T cell receptor (pre-TCR) is a pTalpha-beta heterodimer functioning in
      early alphabeta T cell development. Although once thought to be ligand
      autonomous, recent studies show that pre-TCRs participate in thymic repertoire
      formation through recognition of peptides bound to major histocompatibility
      molecules (pMHC). Using optical tweezers, we probe pre-TCR bonding with pMHC at
      the single molecule level. Like the alphabetaTCR, the pre-TCR is a mechanosensor
      undergoing force-based structural transitions that dynamically enhance bond
      lifetimes and exploiting allosteric control regulated via the Cbeta FG loop
      region. The pre-TCR structural transitions exhibit greater reversibility than
      TCRalphabeta and ordered force-bond lifetime curves. Higher piconewton force
      requires binding through both complementarity determining region loops and
      hydrophobic Vbeta patch apposition. This patch functions in the pre-TCR as a
      surrogate Valpha domain, fostering ligand promiscuity to favor development of
      beta chains with self-reactivity but is occluded by alpha subunit replacement of
      pTalpha upon alphabetaTCR formation. At the double negative 3 thymocyte stage
      where the pre-TCR is first expressed, pre-TCR interaction with self-pMHC ligands
      imparts growth and survival advantages as revealed in thymic stromal cultures,
      imprinting fundamental self-reactivity in the T cell repertoire. Collectively,
      our data imply the existence of sequential mechanosensor alphabetaTCR repertoire
      tuning via the pre-TCR.

PMID- 27707883
TI  - Protein kinase CK2 controls T-cell polarization through dendritic cell activation
      in response to contact sensitizers.
AB  - Allergic contact dermatitis (ACD) represents a severe health problem with
      increasing worldwide prevalence. It is a T-cell-mediated inflammatory skin
      disease caused by chemicals present in the daily or professional environment.
      NiSO4 and 2,4-dinitrochlorobenzene (DNCB) are 2 chemicals involved in ACD. These
      contact sensitizers are known to induce an up-regulation of phenotypic markers
      and cytokine secretion in dendritic cells (DCs; professional APCs), leading to
      the generation of CD8+ Tc1/Tc17 and CD4+ Th1/Th17 effector T cells. In the
      present study, using a peptide array approach, we identified protein kinase CK2
      as a novel kinase involved in the activation of human monocyte-derived DCs
      (MoDCs) in response to NiSO4 and DNCB. Inhibition of CK2 activity in MoDCs led to
      an altered mature phenotype with lower expression of CD54, PDL-1, CD86, and CD40
      in response to NiSO4 or DNCB. CK2 activity also regulated proinflammatory
      cytokine production, such as TNF-alpha, IL-1beta, and IL-23 in MoDCs. Moreover,
      in a DC/T cell coculture model in an allogeneic setup, CK2 activity in MoDCs
      played a major role in Th1 polarization in response to NiSO4 and DNCB. CK2
      inhibition in MoDCs led to an enhanced Th2 polarization in the absence of contact
      sensitizer stimulation.

PMID- 27707882
TI  - IFN-gamma targets macrophage-mediated immune responses toward Staphylococcus
      aureus.
AB  - Infections, especially with Staphylococcus aureus (SA), commonly cause morbidity
      and mortality in patients with chronic granulomatous disease (CGD), a condition
      characterized by a defective phagocyte oxidase. IFN-gamma reduces the frequency
      and consequences of infection in CGD by mechanisms that remain unknown. As IFN
      gamma promotes bacterial killing, efferocytosis of effete polymorphonuclear
      neutrophils (PMN), and cytokine production in macrophages-the same macrophage
      effector functions that are impaired in response to SA-we hypothesized that IFN
      gamma may reverse these defects and thereby, augment macrophage control of SA
      during infection. IFN-gamma primed activation of the NADPH oxidase in a time
      dependent manner, enhanced killing of ingested SA independent of any effects on
      phagocytosis, and increased binding of SA-laden neutrophils (PMN-SA) to
      macrophages. However, IFN-gamma did not increase the percentage of apoptotic PMN
      or PMN-SA internalized by macrophages. Under conditions in which viable SA were
      eliminated, PMN-SA primed the inflammasome for subsequent activation by silica
      but did not induce IL-1beta production by macrophages. IFN-gamma enhanced IL-6
      production in response to SA or PMN-SA but did not increase inflammasome
      activation in response to either agonist. In summary, IFN-gamma augmented direct
      killing of SA by macrophages, promoted engagement of PMN-SA, and enhanced
      macrophage-mediated cytokine responses that could collectively augment control of
      SA infection. Together, these findings support the hypothesis that IFN-gamma
      improves responsiveness of macrophages to SA and provides insights into the
      mechanism of the clinical benefits of IFN-gamma.

PMID- 27707884
TI  - Ikaros 6 protects acute lymphoblastic leukemia cells against daunorubicin-induced
      apoptosis by activating the Akt-FoxO1 pathway.
AB  - Ikaros isoform 6 (Ik6) is associated with a poor prognosis for children with
      acute lymphoblastic leukemia (ALL). Our previous study demonstrated that
      overexpression of Ik6 enhances proliferation and chemoresistance of leukemia
      cells, with a possible underlying mechanism that involves antiapoptosis. In the
      present study, we investigated whether Ik6 protects against apoptosis by
      regulating the Akt-FoxO1 pathway. Bone marrow samples from children with ALL were
      collected and evaluated. In Ik6+ patients, the Akt-FoxO1 pathway was activated
      such that expression of phosphorylated Akt and FoxO1 was significantly increased,
      but that of Bim and p27 decreased. In vitro experiments in this study were
      performed by using human ALL Nalm-6 cells that were stably transfected with Ik6
      (Nalm-6/Ik6) or Sup-B15 and Ik6 shRNA (Sup-B15/Ik6 shRNA). Upon treatment with
      daunorubicin, Nalm-6/Ik6 cells exhibited a statistically significant reduction in
      apoptosis, with increased expression of p-Akt and p-FoxO1. In contrast, an
      increase in apoptosis with decreased expression of p-Akt and p-FoxO1 was observed
      in Sup-B15/Ik6 shRNA cells. This protection was dependent on activation of
      caspase-3 cleavage. By using an activator and an inhibitor of Akt or FoxO1, we
      demonstrated that Akt or FoxO1 activation had no effect on Ik6 expression. In
      conclusion, Ik6, the upstream factor of Akt-FoxO1 pathway, can protect ALL cells
      against daunorubicin-induced apoptosis and can potentially be explored as a
      therapeutic target in the treatment of patients with ALL.

PMID- 27707885
TI  - Financial Strain, Parental Smoking, and the Great Recession: An Analysis of the
      UK Millennium Cohort Study.
AB  - Introduction: During the recent "Great Recession," many families in the United
      Kingdom experienced increased financial strain (FS). The aim of this study was to
      determine if increases in FS, occurring over the period of the "Great Recession,"
      were associated with increased risks of persistent and relapsed tobacco use among
      parents. Methods: We analyzed the Millennium Cohort Study, a longitudinal study
      of 18819 children born in the United Kingdom between 2000 and 2002. Surveys at 7
      (T1, 2008) and 11 years (T2, 2012) spanned the "Great Recession." Three measures
      of increased FS were defined; "became income poor" (self-reported household
      income dropped below the "poverty line" between T1 and T2); "developed difficulty
      managing" (parental report of being "financially comfortable" at T1 and finding
      it "difficult to manage" at T2); "felt worse off" (parental report of feeling
      financially "worse off" at T2, compared to T1). Poisson regression was used to
      estimate risk ratios (RR), adjusted RRs (aRR), and 95% confidence intervals for
      three outcomes: "persistent tobacco use," "new reported tobacco use," and
      "relapsed tobacco use." Results: Parents in households which "became income poor"
      over the period of the "Great Recession" were significantly more likely to report
      "persistent tobacco use" (aRR = 2.17 [1.83-2.57]) or "new reported tobacco use"
      (aRR = 1.72 [1.04-2.83]). Ninety-five percent of "new reported tobacco users" had
      evidence of prior tobacco use suggesting the majority were "relapsed tobacco
      users." Similar patterns were seen for those who "developed difficulty managing"
      and "felt worse off." Conclusions: Increased tobacco use among financially
      strained families has the potential to widen inequalities and undermine the
      public health policies that have had positive impacts on tobacco consumption in
      the United Kingdom. Implications: While several studies have shown that FS is
      associated with a higher prevalence of tobacco use, heavier smoking, and relapsed
      tobacco use, most of this work used cross-sectional data and none has focused on
      parents. We used longitudinal data from the UK Millennium Cohort Study, between
      2008 and 2012, to examine the association between FS and parental smoking. We
      show that parents who experienced increased FS, over the period of the "Great
      Recession," were more likely to continue using tobacco or to relapse.

PMID- 27707886
TI  - Exploitation of Castration-Resistant Prostate Cancer Transcription Factor
      Dependencies by the Novel BET Inhibitor ABBV-075.
AB  - : Competitive inhibitors of acetyl-lysine binding to the bromodomains of the BET
      (bromodomain and extra terminal) family are being developed for the treatment of
      solid and hematologic malignancies. The function of BET family member BRD4 at
      enhancers/superenhancers has been shown to sustain signal-dependent or pathogenic
      gene expression programs. Here, the hypothesis was tested that the transcription
      factor drivers of castration-resistant prostate cancer (CRPC) clinical
      progression, including the androgen receptor (AR), are critically dependent on
      BRD4 and thus represent a sensitive solid tumor indication for the BET inhibitor
      ABBV-075. DHT-stimulated transcription of AR target genes was inhibited by ABBV
      075 without significant effect on AR protein expression. Furthermore, ABBV-075
      disrupted DHT-stimulated recruitment of BET family member BRD4 to gene-regulatory
      regions cooccupied by AR, including the well-established PSA and TMPRSS2
      enhancers. Persistent BET inhibition disrupted the composition and function of AR
      occupied enhancers as measured by a reduction in AR and H3K27Ac ChIP signal and
      inhibition of enhancer RNA transcription. ABBV-075 displayed potent
      antiproliferative activity in multiple models of resistance to second-generation
      antiandrogens and inhibited the activity of the AR splice variant AR-V7 and
      ligand-binding domain gain-of-function mutations, F877L and L702H. ABBV-075 was
      also a potent inhibitor of MYC and the TMPRSS2-ETS fusion protein, important
      parallel transcription factor drivers of CRPC. IMPLICATIONS: The ability of BET
      family inhibitor ABBV-075 to inhibit transcription activation downstream of the
      initiating events of transcription factors like AR and TMPRSS2:ETS fusion
      proteins provides a promising therapeutic option for CRPC patients who have
      developed resistance to second-generation antiandrogens. Mol Cancer Res; 15(1);
      35-44. (c)2016 AACR.

PMID- 27707887
TI  - Overcoming EGFR Bypass Signal-Induced Acquired Resistance to ALK Tyrosine Kinase
      Inhibitors in ALK-Translocated Lung Cancer.
AB  - : Activation of the EGFR pathway is one of the mechanisms inducing acquired
      resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI)
      such as crizotinib and alectinib. Ceritinib is a highly selective ALK inhibitor
      and shows promising efficacy in non-small cell lung cancers (NSCLC) harboring the
      ALK gene rearrangement. However, the precise mechanism underlying acquired
      resistance to ceritinib is not well-defined. This study set out to clarify the
      mechanism in ALK-translocated lung cancer and to find the preclinical rationale
      overcoming EGFR pathway-induced acquired resistance to ALK-TKIs. To this end,
      ceritinib-resistant cells (H3122-CER) were established from the H3122 NSCLC cell
      line harboring the ALK gene rearrangement via long-term exposure to ceritinib.
      H3122-CER cells acquired resistance to ceritinib through EGFR bypass pathway
      activation. Furthermore, H3122 cells that became resistant to ceritinib or
      alectinib through EGFR pathway activation showed cross-resistance to other ALK
      TKIs. Ceritinib and afatinib combination treatment partially restored the
      sensitivity to ceritinib. IMPLICATIONS: This study proposes a preclinical
      rationale to use ALK-TKIs and afatinib combination therapy for ALK-translocated
      lung cancers that have acquired resistance to ALK-TKIs through EGFR pathway
      activation. Mol Cancer Res; 15(1); 106-14. (c)2016 AACR.

PMID- 27707889
TI  - Analysis of Arabidopsis Accessions Hypersensitive to a Loss of Chloroplast
      Translation.
AB  - Natural accessions of Arabidopsis (Arabidopsis thaliana) differ in their ability
      to tolerate a loss of chloroplast translation. These differences can be
      attributed in part to variation in a duplicated nuclear gene (ACC2) that targets
      homomeric acetyl-coenzyme A carboxylase (ACCase) to plastids. This functional
      redundancy allows limited fatty acid biosynthesis to occur in the absence of
      heteromeric ACCase, which is encoded in part by the plastid genome. In the
      presence of functional ACC2, tolerant alleles of several nuclear genes, not yet
      identified, enhance the growth of seedlings and embryos disrupted in chloroplast
      translation. ACC2 knockout mutants, by contrast, are hypersensitive. Here we
      describe an expanded search for hypersensitive accessions of Arabidopsis,
      evaluate whether all of these accessions are defective in ACC2, and characterize
      genotype-to-phenotype relationships for homomeric ACCase variants identified
      among 855 accessions with sequenced genomes. Null alleles with ACC2 nonsense
      mutations, frameshift mutations, small deletions, genomic rearrangements, and
      defects in RNA splicing are included among the most sensitive accessions
      examined. By contrast, most missense mutations affecting highly conserved
      residues failed to eliminate ACC2 function. Several accessions were identified
      where sensitivity could not be attributed to a defect in either ACC2 or Tic20-IV,
      the chloroplast membrane channel required for ACC2 uptake. Overall, these results
      underscore the central role of ACC2 in mediating Arabidopsis response to a loss
      of chloroplast translation, highlight future applications of this system to
      analyzing chloroplast protein import, and provide valuable insights into the
      mutational landscape of an important metabolic enzyme that is highly conserved
      throughout eukaryotes.

PMID- 27707891
TI  - Employing imaginative rationality: using metaphor when discussing death.
AB  - The prevalence of metaphors in medicine is widely acknowledged. In a qualitative
      study exploring expectations of longevity, we observed repeated recourse to the
      imaginative rationality provided by metaphors to express perspectives on
      longevity and death. Bafflement, acceptance, uncertainty and distress were
      conveyed through metaphors, providing valuable insight into the internal
      healthcare frameworks of participants. Skilful use of imaginative rationality in
      the healthcare setting may illuminate the elusive and often eschewed topic of
      death in a way that fosters clarity and new understandings, and pave the way
      towards a better life, and death for patients. By becoming aware of the nuances
      contained within patients'-as well as their own-metaphors, clinicians may enhance
      patients' overall healthcare experience and avert unintended miscommunication.

PMID- 27707890
TI  - A Single Arabidopsis Gene Encodes Two Differentially Targeted Geranylgeranyl
      Diphosphate Synthase Isoforms.
AB  - A wide diversity of isoprenoids is produced in different plant compartments. Most
      groups of isoprenoids synthesized in plastids, and some produced elsewhere in the
      plant cell derive from geranylgeranyl diphosphate (GGPP) synthesized by GGPP
      synthase (GGPPS) enzymes. In Arabidopsis (Arabidopsis thaliana), five genes
      appear to encode GGPPS isoforms localized in plastids (two), the endoplasmic
      reticulum (two), and mitochondria (one). However, the loss of function of the
      plastid-targeted GGPPS11 isoform (referred to as G11) is sufficient to cause
      lethality. Here, we show that the absence of a strong transcription initiation
      site in the G11 gene results in the production of transcripts of different
      lengths. The longer transcripts encode an isoform with a functional plastid
      import sequence that produces GGPP for the major groups of photosynthesis-related
      plastidial isoprenoids. However, shorter transcripts are also produced that lack
      the first translation initiation codon and rely on a second in-frame ATG codon to
      produce an enzymatically active isoform lacking this N-terminal domain. This
      short enzyme localizes in the cytosol and is essential for embryo development.
      Our results confirm that the production of differentially targeted enzyme
      isoforms from the same gene is a central mechanism to control the biosynthesis of
      isoprenoid precursors in different plant cell compartments.

PMID- 27707888
TI  - Hydrocarbons Are Essential for Optimal Cell Size, Division, and Growth of
      Cyanobacteria.
AB  - Cyanobacteria are intricately organized, incorporating an array of internal
      thylakoid membranes, the site of photosynthesis, into cells no larger than other
      bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in
      substantial production of hydrocarbons in the environment. All sequenced
      cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting an important,
      undefined physiological role for these compounds. Here, we demonstrate that
      hydrocarbon-deficient mutants of Synechococcus sp. PCC 7002 and Synechocystis sp.
      PCC 6803 exhibit significant phenotypic differences from wild type, including
      enlarged cell size, reduced growth, and increased division defects.
      Photosynthetic rates were similar between strains, although a minor reduction in
      energy transfer between the soluble light harvesting phycobilisome complex and
      membrane-bound photosystems was observed. Hydrocarbons were shown to accumulate
      in thylakoid and cytoplasmic membranes. Modeling of membranes suggests these
      compounds aggregate in the center of the lipid bilayer, potentially promoting
      membrane flexibility and facilitating curvature. In vivo measurements confirmed
      that Synechococcus sp. PCC 7002 mutants lacking hydrocarbons exhibit reduced
      thylakoid membrane curvature compared to wild type. We propose that hydrocarbons
      may have a role in inducing the flexibility in membranes required for optimal
      cell division, size, and growth, and efficient association of soluble and
      membrane bound proteins. The recent identification of C15-C17 alkanes and alkenes
      in microalgal species suggests hydrocarbons may serve a similar function in a
      broad range of photosynthetic organisms.

PMID- 27707892
TI  - Laboratory Response to 2014 Ebola Virus Outbreak in Mali.
AB  - Aware of the rapid spread of Ebola virus (EBOV) during the current West African
      epidemic, Mali took several proactive steps to rapidly identify cases within its
      borders. Under the Mali International Center for Excellence in Research program,
      a collaboration between the National Institute of Allergy and Infectious Diseases
      and the Malian Ministry of Higher Education and Scientific Research established a
      national EBOV diagnostic site at the University of Sciences, Techniques and
      Technologies of Bamako in the SEREFO Laboratory. Two separate introductions of
      EBOV occurred in Mali from neighboring Guinea, but both chains of transmission
      were quickly halted, and Mali was declared "Ebola free" on 18 January 2015 and
      has remained so since. The SEREFO Laboratory was instrumental in the success of
      Mali's Ebola response by providing timely and accurate diagnostics. As of today,
      the SEREFO Laboratory has tested 103 samples from 88 suspected cases, 10 of which
      were EBOV positive, since the Ebola diagnostics unit started in April 2014. The
      establishment of Ebola diagnostics in the SEREFO Laboratory, safety precautions,
      and diagnostics are described.

PMID- 27707893
TI  - More Challenges From Ebola: Infection of the Central Nervous System.
AB  - Cases of relapsed Ebola virus disease involving symptoms in the central nervous
      system are reminiscent of our past observations with some nonhuman primates
      (NHPs) that survived acute Ebola virus infection. We document our findings in
      detail here and suggest that this phenomenon can be further investigated in NHPs.

PMID- 27707894
TI  - Neocortex expansion is linked to size variations in gene families with
      chemotaxis, cell-cell signalling and immune response functions in mammals.
AB  - Increased brain size is thought to have played an important role in the evolution
      of mammals and is a highly variable trait across lineages. Variations in brain
      size are closely linked to corresponding variations in the size of the neocortex,
      a distinct mammalian evolutionary innovation. The genomic features that explain
      and/or accompany variations in the relative size of the neocortex remain unknown.
      By comparing the genomes of 28 mammalian species, we show that neocortical
      expansion relative to the rest of the brain is associated with variations in gene
      family size (GFS) of gene families that are significantly enriched in biological
      functions associated with chemotaxis, cell-cell signalling and immune response.
      Importantly, we find that previously reported GFS variations associated with
      increased brain size are largely accounted for by the stronger link between
      neocortex expansion and variations in the size of gene families. Moreover, genes
      within these families are more prominently expressed in the human neocortex
      during early compared with adult development. These results suggest that changes
      in GFS underlie morphological adaptations during brain evolution in mammalian
      lineages.

PMID- 27707895
TI  - Streptococcal group B integrative and mobilizable element IMESag-rpsI encodes a
      functional relaxase involved in its transfer.
AB  - Streptococcus agalactiae or Group B Streptococcus (GBS) are opportunistic
      bacteria that can cause lethal sepsis in children and immuno-compromised
      patients. Their genome is a reservoir of mobile genetic elements that can be
      horizontally transferred. Among them, integrative and conjugative elements (ICEs)
      and the smaller integrative and mobilizable elements (IMEs) primarily reside in
      the bacterial chromosome, yet have the ability to be transferred between cells by
      conjugation. ICEs and IMEs are therefore a source of genetic variability that
      participates in the spread of antibiotic resistance. Although IMEs seem to be the
      most prevalent class of elements transferable by conjugation, they are poorly
      known. Here, we have studied a GBS-IME, termed IMESag-rpsI, which is widely
      distributed in GBS despite not carrying any apparent virulence trait. Analyses of
      240 whole genomes showed that IMESag-rpsI is present in approximately 47% of the
      genomes, has a roughly constant size (approx. 9 kb) and is always integrated at a
      single location, the 3'-end of the gene encoding the ribosomal protein S9 (rpsI).
      Based on their genetic variation, several IMESag-rpsI types were defined (A-J)
      and classified in clonal complexes (CCs). CC1 was the most populated by IMESag
      rpsI (more than 95%), mostly of type-A (71%). One CC1 strain (S. agalactiae HRC)
      was deep-sequenced to understand the rationale underlying type-A IMESag-rpsI
      enrichment in GBS. Thirteen open reading frames were identified, one of them
      encoding a protein (MobSag) belonging to the broadly distributed family of
      relaxases MOBV1 Protein MobSag was purified and, by a newly developed method,
      shown to cleave DNA at a specific dinucleotide. The S. agalactiae HRC-IMESag-rpsI
      is able to excise from the chromosome, as shown by the presence of circular
      intermediates, and it harbours a fully functional mobilization module. Further,
      the mobSag gene encoded by this mobile element is able to promote plasmid
      transfer among pneumococcal strains, suggesting that MobSag facilitates the
      spread of IMESag-rpsI and that this spread would explain the presence of the same
      IMESag-rpsI type in GBS strains belonging to different CCs.

PMID- 27707896
TI  - Health-related behaviours and mental health in Hong Kong employees.
AB  - BACKGROUND: Poor physical and mental health in employees can result in a serious
      loss of productivity. Early detection and management of unhealthy behaviours and
      mental health symptoms can prevent productivity loss and foster healthy
      workplaces. AIMS: To examine health-related behaviours, mental health status and
      help-seeking patterns in employees, across different industries in Hong Kong.
      METHODS: Participants were telephone-interviewed and assessed using the Case
      finding and Help Assessment Tool (CHAT) with employee lifestyle risk factors,
      mental health issues and help-seeking intentions screened across eight
      industries. Subsequent data analysis involved descriptive statistics and chi
      square tests. RESULTS: There were 1031 participants. Key stressors were work
      (30%), family (19%), money (14%) and interpersonal issues (5%). Approximately 18,
      9 and 9% of participants were smokers, drinkers and gamblers, respectively, and
      only 51% exercised regularly. Depressive and anxiety symptoms were reported by 24
      and 31% of employees, respectively. Issues for which they wanted immediate help
      were interpersonal abuse (16%), anxiety (15%), anger control (14%) and depression
      (14%). Employees with higher educational attainment were less likely to smoke,
      drink and gamble than those with lower attainment. Lifestyle and mental health
      status were not associated with income. Employees in construction and hotel
      industries smoked more and those in manufacturing drank more than those in other
      industries. CONCLUSIONS: Physical and mental health of Hong Kong employees are
      concerning. Although employee assistance programmes are common among large
      companies, initiation of proactive engagement approaches, reaching out to those
      employees in need and unlikely to seek help for mental health issues, may be
      useful.

PMID- 27707897
TI  - Are inspectors' assessments reliable? Ratings of NHS acute hospital trust
      services in England.
AB  - The credibility of a regulator could be threatened if stakeholders perceive that
      assessments of performance made by its inspectors are unreliable. Yet there is
      little published research on the reliability of inspectors' assessments of health
      care organizations' services. Objectives We investigated the inter-rater
      reliability of assessments made by inspectors inspecting acute hospitals in
      England during the piloting of a new regulatory model implemented by the Care
      Quality Commission (CQC) during 2013 and 2014. Multi-professional teams of
      inspectors rated service provision on a four-point scale for each of five
      domains: safety; effectiveness; caring; responsiveness; and leadership. Methods
      In an online survey, we asked individual inspectors to assign a domain and a
      rating to each of 10 vignettes of service information extracted from CQC
      inspection reports. We used these data to simulate the ratings that might be
      produced by teams of inspectors. We also observed inspection teams in action, and
      interviewed inspectors and staff from hospitals that had been inspected. Results
      Levels of agreement varied substantially from vignette to vignette.
      Characteristics such as professional background explained only a very small part
      of the variation. Overall, agreement was higher on ratings than on domains, and
      for groups of inspectors compared with individual inspectors. A number of
      potential causes of disagreement were identified, such as differences regarding
      the weight that should be given to contextual factors and general uncertainty
      about interpreting the rating and domain categories. Conclusion Groups of
      inspectors produced more reliable assessments than individual inspectors, and
      there is evidence to support the utility of appropriate discussions between
      inspectors in improving reliability. The reliability of domain allocations was
      lower than for ratings. It is important to define categories and rating levels
      clearly, and to train inspectors in their use. Further research is needed to
      replicate these results now that the model has been fully implemented, and to
      understand better the impact that inspector uncertainty and disagreement may have
      on published CQC ratings.

PMID- 27707899
TI  - Small-Molecule Disruption of the Myb/p300 Cooperation Targets Acute Myeloid
      Leukemia Cells.
AB  - The transcription factor c-Myb is essential for the proliferation of
      hematopoietic cells and has been implicated in the development of leukemia and
      other human cancers. Pharmacologic inhibition of Myb is therefore emerging as a
      potential therapeutic strategy for these diseases. By using a Myb reporter cell
      line, we have identified plumbagin and several naphthoquinones as potent low
      molecular weight Myb inhibitors. We demonstrate that these compounds inhibit c
      Myb by binding to the c-Myb transactivation domain and disrupting the cooperation
      of c-Myb with the coactivator p300, a major driver of Myb activity.
      Naphthoquinone-induced inhibition of c-Myb suppresses Myb target gene expression
      and induces the differentiation of the myeloid leukemia cell line HL60. We
      demonstrate that murine and human primary acute myeloid leukemia cells are more
      sensitive to naphthoquinone-induced inhibition of clonogenic proliferation than
      normal hematopoietic progenitor cells. Overall, our work demonstrates for the
      first time the potential of naphthoquinones as small-molecule Myb inhibitors that
      may have therapeutic potential for the treatment of leukemia and other tumors
      driven by deregulated Myb. Mol Cancer Ther; 15(12); 2905-15. (c)2016 AACR.

PMID- 27707900
TI  - Patient- and Visit-Level Variables Associated With Late Arrival to Pediatric
      Clinic Appointments.
AB  - We conducted a cross-sectional study to evaluate timeliness of patient arrival at
      a pediatric multispecialty clinic. Bivariate and ordered logistic regression
      analyses were conducted to determine the odds of late arrival by specified
      patient- and visit-level characteristics. A total of 64 856 visits were available
      for analysis, of which 6513 (10.0%) were late arrivals. The odds of late arrival
      were higher for patients who spoke English (odds ratio [OR] = 1.34, P < .001)
      compared with those who spoke Spanish, had Medicaid (OR = 1.54, P < .001) or no
      insurance (OR = 1.49, P < .001) compared with those with insurance other than
      Medicaid, and were late to their previous visit (OR = 2.46, P < .001). Visit
      level variables associated with late arrival included appointment time earlier in
      the day (i.e. 8-10 am, OR = 2.77, P < .001 compared with 4-6 pm), earlier in the
      week (i.e. on Mondays, OR = 1.21, P < .001 compared with Wednesdays), and for
      certain subspecialty clinics ( P < .001). Numerous variables are significantly
      associated with late arrival for pediatric clinic appointments.

PMID- 27707901
TI  - Complementary and Alternative Medicine Use in Modern Obstetrics: A Survey of the
      Central Association of Obstetricians & Gynecologists Members.
AB  - The use of complementary and alternative medicine during pregnancy is currently
      on the rise. A validated survey was conducted at the Central Association of
      Obstetrician and Gynecologists annual meeting to evaluate the knowledge,
      attitude, and practice of general obstetricians and gynecologists and maternal
      fetal medicine specialists in America. We obtained 128 responses: 73
      electronically (57%) and 55 via the paper survey (43%). Forty-five percent
      reported personally using complementary and alternative medicine and 9% of women
      respondents used complementary and alternative medicine during pregnancy.
      Overall, 62% had advised their patients to utilize some form of complementary and
      alternative medicine in pregnancy. Biofeedback, massage therapy, meditation, and
      yoga were considered the most effective modalities in pregnancy (median [semi
      interquartile range] = 2 [0.5]). Maternal-fetal medicine specialists were
      significantly more likely to disagree on the use of complementary and alternative
      medicine for risk reduction of preterm birth compared to obstetricians and
      gynecologists ( P = .03). As the use of complementary and alternative medicine
      continues to rise in reproductive-age women, obstetricians will play an integral
      role in incorporating complementary and alternative medicine use with
      conventional medicine.

PMID- 27707902
TI  - The Significance of Ayurvedic Medicinal Plants.
AB  - Traditional Indian medicine (ayurveda) is becoming increasingly popular, with
      many chronic conditions responding to it well. Most patients begin to take
      conventional medications as soon as their diagnoses are made, so ayurvedic
      treatments are usually undergone alongside and/or after conventional medical
      approaches. A detailed knowledge of the action of food, spices, and medicinal
      plants is needed in order to understand their potential influence fully. While
      societal use of ayurvedic plants and Indian spices is commonplace, without ill
      effect, the use of more concentrated products made from single plants, often in
      the form of teas or tablets, is of more concern. The mechanisms by which
      polyherbal drugs and their extracts act differ in many respects from the actions
      of single substances or synthetic drugs. Despite the fact that ayurvedic
      medicines are based on natural herbal materials, their safety depends on their
      method of administration, taking into account individuals' needs and their
      specific disease conditions.

PMID- 27707903
TI  - Fruit fly scale robots can hover longer with flapping wings than with spinning
      wings.
AB  - Hovering flies generate exceptionally high lift, because their wings generate a
      stable leading edge vortex. Micro flying robots with a similar wing design can
      generate similar high lift by either flapping or spinning their wings. While it
      requires less power to spin a wing, the overall efficiency depends also on the
      actuator system driving the wing. Here, we present the first holistic analysis to
      calculate how long a fly-inspired micro robot can hover with flapping versus
      spinning wings across scales. We integrate aerodynamic data with data-driven
      scaling laws for actuator, electronics and mechanism performance from fruit fly
      to hummingbird scales. Our analysis finds that spinning wings driven by rotary
      actuators are superior for robots with wingspans similar to hummingbirds, yet
      flapping wings driven by oscillatory actuators are superior at fruit fly scale.
      This crossover is driven by the reduction in performance of rotary compared with
      oscillatory actuators at smaller scale. Our calculations emphasize that a systems
      level analysis is essential for trading-off flapping versus spinning wings for
      micro flying robots.

PMID- 27707904
TI  - The role of amino acids in hydroxyapatite mineralization.
AB  - Polar and charged amino acids (AAs) are heavily expressed in non-collagenous
      proteins (NCPs), and are involved in hydroxyapatite (HA) mineralization in bone.
      Here, we review what is known on the effect of single AAs on HA precipitation.
      Negatively charged AAs, such as aspartic acid, glutamic acid (Glu) and
      phosphoserine are largely expressed in NCPs and play a critical role in
      controlling HA nucleation and growth. Positively charged ones such as arginine
      (Arg) or lysine (Lys) are heavily involved in HA nucleation within extracellular
      matrix proteins such as collagen. Glu, Arg and Lys intake can also increase bone
      mineral density by stimulating growth hormone production. In vitro studies
      suggest that the role of AAs in controlling HA precipitation is affected by their
      mobility. While dissolved AAs are able to inhibit HA precipitation and growth by
      chelating Ca2+ and PO43- ions or binding to nuclei of calcium phosphate and
      preventing their further growth, AAs bound to surfaces can promote HA
      precipitation by attracting Ca2+ and PO43- ions and increasing the local
      supersaturation. Overall, the effect of AAs on HA precipitation is worth being
      investigated more, especially under conditions closer to the physiological ones,
      where the presence of other factors such as collagen, mineralization inhibitors,
      and cells heavily influences HA precipitation. A deeper understanding of the role
      of AAs in HA mineralization will increase our fundamental knowledge related to
      bone formation, and could lead to new therapies to improve bone regeneration in
      damaged tissues or cure pathological diseases caused by excessive mineralization
      in tissues such as cartilage, blood vessels and cardiac valves.

PMID- 27707905
TI  - Role of intracellular poroelasticity on freezing-induced deformation of cells in
      engineered tissues.
AB  - Freezing of biomaterials is important in a wide variety of biomedical
      applications, including cryopreservation and cryosurgeries. For the success of
      these applications to various biomaterials, biophysical mechanisms, which
      determine freezing-induced changes in cells and tissues, need to be well
      understood. Specifically, the significance of the intracellular mechanics during
      freezing is not well understood. Thus, we hypothesize that cells interact during
      freezing with the surroundings such as suspension media and the extracellular
      matrix (ECM) via two distinct but related mechanisms-water transport and
      cytoskeletal mechanics. The underlying rationale is that the cytoplasm of the
      cells has poroelastic nature, which can regulate both cellular water transport
      and cytoskeletal mechanics. A poroelasticity-based cell dehydration model is
      developed and confirmed to provide insight into the effects of the hydraulic
      conductivity and stiffness of the cytoplasm on the dehydration of cells in
      suspension during freezing. We further investigated the effect of the
      cytoskeletal structures on the cryoresponse of cells embedded in the ECM by
      measuring the spatio-temporal intracellular deformation with dermal equivalent as
      a model tissue. The freezing-induced change in cell, nucleus and cytoplasm volume
      was quantified, and the possible mechanism of the volumetric change was proposed.
      The results are discussed considering the hierarchical poroelasticity of
      biological tissues.

PMID- 27707906
TI  - Trade-off between disease resistance and crop yield: a landscape-scale
      mathematical modelling perspective.
AB  - The deployment of crop varieties that are partially resistant to plant pathogens
      is an important method of disease control. However, a trade-off may occur between
      the benefits of planting the resistant variety and a yield penalty, whereby the
      standard susceptible variety outyields the resistant one in the absence of
      disease. This presents a dilemma: deploying the resistant variety is advisable
      only if the disease occurs and is sufficient for the resistant variety to
      outyield the infected standard variety. Additionally, planting the resistant
      variety carries with it a further advantage in that the resistant variety reduces
      the probability of disease invading. Therefore, viewed from the perspective of a
      grower community, there is likely to be an optimal trade-off and thus an optimal
      cropping density for the resistant variety. We introduce a simple stochastic,
      epidemiological model to investigate the trade-off and the consequences for crop
      yield. Focusing on susceptible-infected-removed epidemic dynamics, we use the
      final size equation to calculate the surviving host population in order to
      analyse the yield, an approach suitable for rapid epidemics in agricultural
      crops. We identify a single compound parameter, which we call the efficacy of
      resistance and which incorporates the changes in susceptibility, infectivity and
      durability of the resistant variety. We use the compound parameter to inform
      policy plots that can be used to identify the optimal strategy for given
      parameter values when an outbreak is certain. When the outbreak is uncertain, we
      show that for some parameter values planting the resistant variety is optimal
      even when it would not be during the outbreak. This is because the resistant
      variety reduces the probability of an outbreak occurring.

PMID- 27707907
TI  - On the possibility of galactic cosmic ray-induced radiolysis-powered life in
      subsurface environments in the Universe.
AB  - Photosynthesis is a mechanism developed by terrestrial life to utilize the energy
      from photons of solar origin for biological use. Subsurface regions are isolated
      from the photosphere, and consequently are incapable of utilizing this energy.
      This opens up the opportunity for life to evolve alternative mechanisms for
      harvesting available energy. Bacterium Candidatus Desulforudis audaxviator, found
      2.8 km deep in a South African mine, harvests energy from radiolysis, induced by
      particles emitted from radioactive U, Th and K present in surrounding rock.
      Another radiation source in the subsurface environments is secondary particles
      generated by galactic cosmic rays (GCRs). Using Monte Carlo simulations, it is
      shown that it is a steady source of energy comparable to that produced by
      radioactive substances, and the possibility of a slow metabolizing life
      flourishing on it cannot be ruled out. Two mechanisms are proposed through which
      GCR-induced secondary particles can be utilized for biological use in subsurface
      environments: (i) GCRs injecting energy in the environment through particle
      induced radiolysis and (ii) organic synthesis from GCR secondaries interacting
      with the medium. Laboratory experiments to test these hypotheses are also
      proposed. Implications of these mechanisms on finding life in the Solar System
      and elsewhere in the Universe are discussed.

PMID- 27707908
TI  - Arsenate reductase from Thermus thermophilus conjugated to polyethylene glycol
      stabilized gold nanospheres allow trace sensing and speciation of arsenic ions.
AB  - Water sources pollution by arsenic ions is a serious environmental problem all
      around the world. Arsenate reductase enzyme (TtArsC) from Thermus thermophilus
      extremophile bacterium, naturally binds arsenic ions, As(V) and As (III), in
      aqueous solutions. In this research, TtArsC enzyme adsorption onto hybrid
      polyethylene glycol-stabilized gold nanoparticles (AuNPs) was studied at
      different pH values as an innovative nanobiosystem for metal concentration
      monitoring. Characterizations were performed by UV/Vis and circular dichroism
      spectroscopies, TEM images and in terms of surface charge changes. The molecular
      interaction between arsenic ions and the TtArsC-AuNPs nanobiosystem was also
      monitored at all pH values considered by UV/Vis spectroscopy. Tests performed
      revealed high sensitivities and limits of detection equal to 10 +/- 3 M-12 and
      7.7 +/- 0.3 M-12 for As(III) and As(V), respectively.

PMID- 27707911
TI  - Introductory paragraph.

PMID- 27707909
TI  - Characterizing the reproduction number of epidemics with early subexponential
      growth dynamics.
AB  - Early estimates of the transmission potential of emerging and re-emerging
      infections are increasingly used to inform public health authorities on the level
      of risk posed by outbreaks. Existing methods to estimate the reproduction number
      generally assume exponential growth in case incidence in the first few disease
      generations, before susceptible depletion sets in. In reality, outbreaks can
      display subexponential (i.e. polynomial) growth in the first few disease
      generations, owing to clustering in contact patterns, spatial effects,
      inhomogeneous mixing, reactive behaviour changes or other mechanisms. Here, we
      introduce the generalized growth model to characterize the early growth profile
      of outbreaks and estimate the effective reproduction number, with no need for
      explicit assumptions about the shape of epidemic growth. We demonstrate this
      phenomenological approach using analytical results and simulations from
      mechanistic models, and provide validation against a range of empirical disease
      datasets. Our results suggest that subexponential growth in the early phase of an
      epidemic is the rule rather the exception. Mechanistic simulations show that
      slight modifications to the classical susceptible-infectious-removed model result
      in subexponential growth, and in turn a rapid decline in the reproduction number
      within three to five disease generations. For empirical outbreaks, the
      generalized-growth model consistently outperforms the exponential model for a
      variety of directly and indirectly transmitted diseases datasets (pandemic
      influenza, measles, smallpox, bubonic plague, cholera, foot-and-mouth disease,
      HIV/AIDS and Ebola) with model estimates supporting subexponential growth
      dynamics. The rapid decline in effective reproduction number predicted by
      analytical results and observed in real and synthetic datasets within three to
      five disease generations contrasts with the expectation of invariant reproduction
      number in epidemics obeying exponential growth. The generalized-growth concept
      also provides us a compelling argument for the unexpected extinction of certain
      emerging disease outbreaks during the early ascending phase. Overall, our
      approach promotes a more reliable and data-driven characterization of the early
      epidemic phase, which is important for accurate estimation of the reproduction
      number and prediction of disease impact.

PMID- 27707912
TI  - Novel role of Vav1-Rac1 pathway in actin cytoskeleton regulation in Interleukin
      13-induced minimal change-like nephropathy.
AB  - Our established interleukin-13 ( IL-13 ) overexpression rat model of minimal
      change-like nephropathy provided a platform to study the molecular signalling
      pathways in T-helper 2 (Th2) cytokine associated minimal change nephrotic
      syndrome. We hypothesized that IL-13 may act directly on podocytes, causing
      podocyte foot process effacement and hence proteinuria in our rat model of
      minimal change-like nephropathy. This study aimed firstly to delineate the
      glomerular "gene signature" associated with IL-13-mediated dysregulation of
      podocyte related proteins, and subsequently to investigate the role of the
      differentially regulated genes in IL-13-mediated podocyte injury. Glomerular
      transcriptional profile of IL-13 -overexpressed rats showed characteristic
      features of podocyte injury with 87% of podocyte related genes being
      significantly down-regulated. Gene expression of Vav1 was shown to be highly up
      regulated in the glomeruli of IL-13 -overexpressed rats and pathway analysis of
      the differentially expressed genes suggested a possible novel role of Vav1 in
      podocyte cytoskeleton remodelling. Immunofluorescence examination demonstrated
      glomerular expression of Vav1 in rats which co-localized with synaptopodin,
      confirming podocyte expression. However, positive staining for the phosphorylated
      form of Vav1 (p-Vav1) was only seen in IL-13 -overexpressed rats. Moreover, in
      vitro IL-13 stimulation of human podocytes resulted in phosphorylation of Vav1.
      This was associated with Rac1 activation and actin cytoskeleton rearrangement,
      which was abrogated in Vav1 knock-down podocytes. In conclusion, we have
      demonstrated the role of Vav1-Rac1 pathway characterised by phosphorylation of
      Vav1, activation of Rac1 and the subsequent actin cytoskeleton rearrangement in
      IL-13 induced podocyte injury, possibly explaining the podocyte foot process
      effacement seen in our IL-13 overexpression rat model.

PMID- 27707910
TI  - Musculoskeletal modelling under an evolutionary perspective: deciphering the role
      of single muscle regions in closely related insects.
AB  - Insects show a remarkable diversity of muscle configurations, yet the factors
      leading to this functional diversity are poorly understood. Here, we use
      musculoskeletal modelling to understand the spatio-temporal activity of an insect
      muscle in several dragonfly species and to reveal potential mechanical factors
      leading to a particular muscle configuration. Bite characteristics potentially
      show systematic signal, but absolute bite force is not correlated with size.
      Muscle configuration and inverse dynamics show that the wider relative area of
      muscle attachment and the higher activity of subapical muscle groups are
      responsible for this high bite force. This wider attachment area is, however, not
      an evolutionary trend within dragonflies. Our inverse dynamic data, furthermore,
      show that maximum bite forces most probably do not reflect maximal muscle force
      production capability in all studied species. The thin head capsule and the
      attachment areas of muscles most probably limit the maximum force output of the
      mandibular muscles.

PMID- 27707913
TI  - Need for Outcome Scenario Analysis of Clinical Trials in Diabetes.
AB  - Since the FDA requirement for cardiovascular safety of all new antihyperglycemic
      drugs to enter the market, the number and extent of phase 3 clinical trials has
      markedly increased. Unexpected trial results imply an enormous economic, personal
      and time cost and has deleterious effects over R&D. To prevent unforeseen
      developments in clinical trials, we recommend performing a comprehensive
      prospective outcome scenario analysis before launching the trial. In this
      commentary, we discuss the most important factors to take in consideration for
      prediction of clinical trial outcome scenarios and propose a theoretical model
      for decision making.

PMID- 27707914
TI  - Patients With Diabetes Monitoring Programs: The Evidence Commands Reform.

PMID- 27707915
TI  - Accuracy Evaluation of a CE-Marked Glucometer System for Self-Monitoring of Blood
      Glucose With Three Reagent Lots Following ISO 15197:2013.
AB  - Continuous standardized verification of the accuracy of blood glucose meter
      systems for self-monitoring after their introduction into the market is an
      important clinically tool to assure reliable performance of subsequently released
      lots of strips. Moreover, such published verification studies permit comparison
      of different blood glucose monitoring systems and, thus, are increasingly
      involved in the process of evidence-based purchase decision making.

PMID- 27707916
TI  - Antibiotic Prescribing by Physicians Versus Nurse Practitioners for Pediatric
      Upper Respiratory Infections.
AB  - BACKGROUND: This study investigates differences in antibiotic prescribing rates
      for pediatric upper respiratory infections (URIs) between physicians and nurse
      practitioners (NPs). METHODS: Visits by children <18 years old diagnosed with URI
      to physicians or NPs between 2001 and 2010 were abstracted from the National
      Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey.
      Logistic regression analyses examined variations in antibiotic prescribing rates.
      RESULTS: Upper respiratory infections accounted for approximately 439 +/- 21.5
      million visits. Patients seen by NPs were more likely to have Medicaid, live in
      the lowest median household income quartile zip codes and micropolitan locations,
      and live in the South compared to patients seen by physicians. Nurse
      practitioners prescribed antibiotics 66.7% +/- 4.2% of the time versus physicians
      at 52.8% +/- 0.8% for URI visits (unadjusted P-value = .002). Adjusted by
      specialty, URI type, and chronic diseases, NPs had marginally significantly
      different odds of prescribing antibiotics (OR = 1.6, 95% CI, 1.0-2.6, P-value =
      .048), but the association with prescribing broad-spectrum antibiotics is not as
      strong (adjusted P-value = .063). Patient visits to a pediatric (OR = 0.54, 95%
      CI, 0.43-0.67) or ENT/surgery practice (OR = 0.11, 95% CI, 0.06-0.18) had lower
      odds of antibiotic prescribing compared to general/family medicine practices.
      Year (2001-2010) was not significantly associated with antibiotic or broad
      spectrum antibiotic prescribing rates for physicians, but rates for NPs fell for
      otitis media (P-value = .007) from 90.2% +/- 8.2% (2001-2002) to 74.8% +/- 6.8%
      (2009-2010) of visits. CONCLUSIONS: Nurse practitioners have higher rates of
      antibiotic prescribing compared to physicians for pediatric patients with URIs;
      however, this difference is less after adjusting for specialty. Examining
      comparative antibiotic prescribing is important to promote evidence-based
      practice and adoption of clinical guidelines.

PMID- 27707917
TI  - Identification of Interferon-Stimulated Gene Proteins That Inhibit Human
      Parainfluenza Virus Type 3.
AB  - : A major arm of cellular innate immunity is type I interferon (IFN), represented
      by IFN-alpha and IFN-beta. Type I IFN transcriptionally induces a large number of
      cellular genes, collectively known as IFN-stimulated gene (ISG) proteins, which
      act as antivirals. The IFIT (interferon-induced proteins with tetratricopeptide
      repeats) family proteins constitute a major subclass of ISG proteins and are
      characterized by multiple tetratricopeptide repeats (TPRs). In this study, we
      have interrogated IFIT proteins for the ability to inhibit the growth of human
      parainfluenza virus type 3 (PIV3), a nonsegmented negative-strand RNA virus of
      the Paramyxoviridae family and a major cause of respiratory disease in children.
      We found that IFIT1 significantly inhibited PIV3, whereas IFIT2, IFIT3, and IFIT5
      were less effective or not at all. In further screening a set of ISG proteins we
      discovered that several other such proteins also inhibited PIV3, including
      IFITM1, IDO (indoleamine 2,3-dioxygenase), PKR (protein kinase, RNA activated),
      and viperin (virus inhibitory protein, endoplasmic reticulum associated,
      interferon inducible)/Cig5. The antiviral effect of IDO, the enzyme that
      catalyzes the first step of tryptophan degradation, could be counteracted by
      tryptophan. These results advance our knowledge of diverse ISG proteins
      functioning as antivirals and may provide novel approaches against PIV3.
      IMPORTANCE: The innate immunity of the host, typified by interferon (IFN), is a
      major antiviral defense. IFN inhibits virus growth by inducing a large number of
      IFN-stimulated gene (ISG) proteins, several of which have been shown to have
      specific antiviral functions. Parainfluenza virus type 3 (PIV3) is major pathogen
      of children, and no reliable vaccine or specific antiviral against it currently
      exists. In this article, we report several ISG proteins that strongly inhibit
      PIV3 growth, the use of which may allow a better antiviral regimen targeting
      PIV3.

PMID- 27707918
TI  - Foot-and-Mouth Disease Virus Viroporin 2B Antagonizes RIG-I-Mediated Antiviral
      Effects by Inhibition of Its Protein Expression.
AB  - : The role of retinoic acid-inducible gene I (RIG-I) in foot-and-mouth disease
      virus (FMDV)-infected cells remains unknown. Here, we showed that RIG-I inhibits
      FMDV replication in host cells. FMDV infection increased the transcription of RIG
      I, while it decreased RIG-I protein expression. A detailed analysis revealed that
      FMDV leader proteinase (Lpro), as well as 3C proteinase (3Cpro) and 2B protein,
      decreased RIG-I protein expression. Lpro and 3Cpro are viral proteinases that can
      cleave various host proteins and are responsible for several of the viral
      polyprotein cleavages. However, for the first time, we observed 2B-induced
      reduction of host protein. Further studies showed that 2B-mediated reduction of
      RIG-I is specific to FMDV, but not other picornaviruses, including
      encephalomyocarditis virus, enterovirus 71, and coxsackievirus A16. Moreover, we
      found the decreased protein level of RIG-I is independent of the cleavage of
      eukaryotic translation initiation factor 4 gamma, the induction of cellular
      apoptosis, or the association of proteasome, lysosome, and caspase pathways. A
      direct interaction was observed between RIG-I and 2B. The carboxyl-terminal amino
      acids 105 to 114 and amino acids 135 to 144 of 2B were essential for the
      reduction of RIG-I, while residues 105 to 114 were required for the interaction.
      These data suggest the antiviral role of RIG-I against FMDV and a novel
      antagonistic mechanism of FMDV that is mediated by 2B protein. IMPORTANCE: This
      study demonstrated that RIG-I could suppress FMDV replication during virus
      infection. FMDV infection increased the transcriptional expression of RIG-I,
      while it decreased RIG-I protein expression. FMDV 2B protein interacted with RIG
      I and induced reduction of RIG-I. 2B-induced reduction of RIG-I was independent
      of the induction of the cleavage of eukaryotic translation initiation factor 4
      gamma or cellular apoptosis. In addition, proteasome, lysosome, and caspase
      pathways were not involved in this process. This study provides new insight into
      the immune evasion mediated by FMDV and identifies 2B as an antagonistic factor
      for FMDV to evade the antiviral response.

PMID- 27707919
TI  - Simian Immunodeficiency Virus-Producing Cells in Follicles Are Partially
      Suppressed by CD8+ Cells In Vivo.
AB  - : Human immunodeficiency virus (HIV)- and simian immunodeficiency virus (SIV)
      specific CD8+ T cells are typically largely excluded from lymphoid B cell
      follicles, where HIV- and SIV-producing cells are most highly concentrated,
      indicating that B cell follicles are somewhat of an immunoprivileged site. To
      gain insights into virus-specific follicular CD8+ T cells, we determined the
      location and phenotype of follicular SIV-specific CD8+ T cells in situ, the local
      relationship of these cells to Foxp3+ cells, and the effects of CD8 depletion on
      levels of follicular SIV-producing cells in chronically SIV-infected rhesus
      macaques. We found that follicular SIV-specific CD8+ T cells were able to migrate
      throughout follicular areas, including germinal centers. Many expressed PD-1,
      indicating that they may have been exhausted. A small subset was in direct
      contact with and likely inhibited by Foxp3+ cells, and a few were themselves
      Foxp3+ In addition, subsets of follicular SIV-specific CD8+ T cells expressed low
      to medium levels of perforin, and subsets were activated and proliferating.
      Importantly, after CD8 depletion, the number of SIV-producing cells increased in
      B cell follicles and extrafollicular areas, suggesting that follicular and
      extrafollicular CD8+ T cells have a suppressive effect on SIV replication. Taken
      together, these results suggest that during chronic SIV infection, despite high
      levels of exhaustion and likely inhibition by Foxp3+ cells, a subset of
      follicular SIV-specific CD8+ T cells are functional and suppress viral
      replication in vivo These findings support HIV cure strategies that augment
      functional follicular virus-specific CD8+ T cells to enhance viral control.
      IMPORTANCE: HIV- and SIV-specific CD8+ T cells are typically largely excluded
      from lymphoid B cell follicles, where virus-producing cells are most highly
      concentrated, suggesting that B cell follicles are somewhat of an
      immunoprivileged site where virus-specific CD8+ T cells are not able to clear all
      follicular HIV- and SIV-producing cells. To gain insights into follicular CD8+ T
      cell function, we characterized follicular virus-specific CD8+ T cells in situ by
      using an SIV-infected rhesus macaque model of HIV. We found that subsets of
      follicular SIV-specific CD8+ T cells are able to migrate throughout the follicle,
      are likely inhibited by Foxp3+ cells, and are likely exhausted but that,
      nonetheless, subsets are likely functional, as they express markers consistent
      with effector function and show signs of suppressing viral replication in vivo
      These findings support HIV cure strategies that increase the frequency of
      functional follicular virus-specific CD8+ T cells.

PMID- 27707920
TI  - Rationally Designed Immunogens Targeting HIV-1 gp120 V1V2 Induce Distinct
      Conformation-Specific Antibody Responses in Rabbits.
AB  - : The V1V2 region of HIV-1 gp120 harbors a major vulnerable site targeted by a
      group of broadly neutralizing monoclonal antibodies (MAbs) such as PG9 through
      strand-strand recognition. However, this epitope region is structurally
      polymorphic as it can also form a helical conformation recognized by RV144
      vaccine-induced MAb CH58. This structural polymorphism is a potential mechanism
      for masking the V1V2 vulnerable site. Designing immunogens that can induce
      conformation-specific antibody (Ab) responses may lead to vaccines targeting this
      vulnerable site. We designed a panel of immunogens engrafting the V1V2 domain
      into trimeric and pentameric scaffolds in structurally constrained conformations.
      We also fused V1V2 to an Fc fragment to mimic the unconstrained V1V2
      conformation. We tested these V1V2-scaffold proteins for immunogenicity in
      rabbits and assessed the responses by enzyme-linked immunosorbent assay (ELISA)
      and competition assays. Our V1V2 immunogens induced distinct conformation
      specific Ab responses. Abs induced by structurally unconstrained immunogens
      reacted preferentially with unconstrained V1V2 antigens, suggesting recognition
      of the helical configuration, while Abs induced by the structurally constrained
      immunogens reacted preferentially with constrained V1V2 antigens, suggesting
      recognition of the beta-strand conformation. The Ab responses induced by the
      structurally constrained immunogens were more broadly reactive and had higher
      titers than those induced by the structurally unconstrained immunogens. Our
      results demonstrate that immunogens presenting the different structural
      conformations of the gp120 V1V2 vulnerable site can be designed and that these
      immunogens induce distinct Ab responses with epitope conformation specificity.
      Therefore, these structurally constrained V1V2 immunogens are vaccine prototypes
      targeting the V1V2 domain of the HIV-1 envelope. IMPORTANCE: The correlates
      analysis of the RV144 HIV-1 vaccine trial suggested that the presence of
      antibodies to the V1V2 region of HIV-1 gp120 was responsible for the modest
      protection observed in the trial. In addition, V1V2 harbors one of the key
      vulnerable sites of HIV-1 Env recognized by a family of broadly neutralizing MAbs
      such as PG9. Thus, V1V2 is a key target for vaccine development. However, this
      vulnerable site is structurally polymorphic, and designing immunogens that
      present different conformations is crucial for targeting this site. We show here
      that such immunogens can be designed and that they induced conformation-specific
      antibody responses in rabbits. Our immunogens are therefore prototypes of vaccine
      candidates targeting the V1V2 region of HIV-1 Env.

PMID- 27707921
TI  - The Intracellular Cholesterol Transport Inhibitor U18666A Inhibits the Exosome
      Dependent Release of Mature Hepatitis C Virus.
AB  - : Hepatitis C virus (HCV) particles are described as lipoviroparticles which are
      released similarly to very-low-density lipoproteins (VLDLs). However, the release
      mechanism is still poorly understood; the canonical endoplasmic reticulum-Golgi
      intermediate compartment (ERGIC) pathway as well as endosome-dependent release
      has been proposed. Recently, the role of exosomes in the transmission of HCV has
      been reported. Only a minor fraction of the de novo-synthesized lipoviroparticles
      is released by the infected cell. To investigate the relevance of multivesicular
      bodies (MVBs) for viral morphogenesis and release, the MVB inhibitor U18666A was
      used. Intracellular trafficking was analyzed by confocal microscopy and electron
      microscopy. Moreover, an mCherry-tagged HCV variant was used. Conditions were
      established that enable U18666A-dependent inhibition of MVBs without affecting
      viral replication. Under these conditions, significant inhibition of the HCV
      release was observed. The assembly of viral particles is not affected. In U18666A
      treated cells, intact infectious viral particles accumulate in CD63-positive
      exosomal structures and large dysfunctional lysosomal structures (multilamellar
      bodies). These retained particles possess a lower density, reflecting a
      misloading with lipids. Our data indicate that at least a fraction of HCV
      particles leaves the cell via the endosomal pathway. Endosomes facilitate the
      sorting of HCV particles for release or degradation. IMPORTANCE: There are still
      a variety of open questions regarding morphogenesis and release of hepatitis C
      virus. The HCV-infected cell produces significant more viral particles that are
      released, raising the question about the fate of the nonreleased particles.
      Moreover, the relevance of the endosomal pathway for the release of HCV is under
      debate. Use of the MVB (multivesicular body) inhibitor U18666A enabled a detailed
      analysis of the impact of MVBs for viral morphogenesis and release. It was
      revealed that infectious, fully assembled HCV particles are either MVB
      dependently released or intracellularly degraded by the lysosome. Our data
      indicate that at least a fraction of HCV particles leaves the cell via the
      endosomal pathway independent from the constitutive secretory pathway. Our study
      describes a so-far-unprecedented cross talk between two pathways regulating on
      the one hand the release of infectious viral particles and on the other hand the
      intracellular degradation of nonreleased particles.

PMID- 27707922
TI  - Syncytial Mutations Do Not Impair the Specificity of Entry and Spread of a
      Glycoprotein D Receptor-Retargeted Herpes Simplex Virus.
AB  - : Membrane fusion, which is the key process for both initial cell entry and
      subsequent lateral spread of herpes simplex virus (HSV), requires the four
      envelope glycoproteins gB, gD, gH, and gL. Syncytial mutations, predominantly
      mapped to the gB and gK genes, confer hyperfusogenicity on HSV and cause
      multinucleated giant cells, termed syncytia. Here we asked whether interaction of
      gD with a cognate entry receptor remains indispensable for initiating membrane
      fusion of syncytial strains. To address this question, we took advantage of
      mutant viruses whose viral entry into cells relies on the uniquely specific
      interaction of an engineered gD with epidermal growth factor receptor (EGFR). We
      introduced selected syncytial mutations into gB and/or gK of the EGFR-retargeted
      HSV and found that these mutations, especially when combined, enabled formation
      of extensive syncytia by human cancer cell lines that express the target
      receptor; these syncytia were substantially larger than the plaques formed by the
      parental retargeted HSV strain. We assessed the EGFR dependence of entry and
      spread separately by using direct entry and infectious center assays,
      respectively, and we found that the syncytial mutations did not override the
      receptor specificity of the retargeted viruses at either stage. We discuss the
      implications of these results for the development of more effective targeted
      oncolytic HSV vectors. IMPORTANCE: Herpes simplex virus (HSV) is investigated not
      only as a human pathogen but also as a promising agent for oncolytic virotherapy.
      We previously showed that both the initial entry and subsequent lateral spread of
      HSV can be retargeted to cells expressing tumor-associated antigens by single
      chain antibodies fused to a receptor-binding-deficient envelope glycoprotein D
      (gD). Here we introduced syncytial mutations into the gB and/or gK gene of gD
      retargeted HSVs to determine whether viral tropism remained dependent on the
      interaction of gD with the target receptor. Entry and spread profiles of the
      recombinant viruses indicated that gD retargeting does not abolish the
      hyperfusogenic activity of syncytial mutations and that these mutations do not
      eliminate the dependence of HSV entry and spread on a specific gD-receptor
      interaction. These observations suggest that syncytial mutations may be valuable
      for increasing the tumor-specific spreading of retargeted oncolytic HSV vectors.

PMID- 27707923
TI  - Heterodimers as the Structural Unit of the T=1 Capsid of the Fungal Double
      Stranded RNA Rosellinia necatrix Quadrivirus 1.
AB  - : Most double-stranded RNA (dsRNA) viruses are transcribed and replicated in a
      specialized icosahedral capsid with a T=1 lattice consisting of 60 asymmetric
      capsid protein (CP) dimers. These capsids help to organize the viral genome and
      replicative complex(es). They also act as molecular sieves that isolate the virus
      genome from host defense mechanisms and allow the passage of nucleotides and
      viral transcripts. Rosellinia necatrix quadrivirus 1 (RnQV1), the type species of
      the family Quadriviridae, is a dsRNA fungal virus with a multipartite genome
      consisting of four monocistronic segments (segments 1 to 4). dsRNA-2 and dsRNA-4
      encode two CPs (P2 and P4, respectively), which coassemble into ~450-A-diameter
      capsids. We used three-dimensional cryo-electron microscopy combined with
      complementary biophysical techniques to determine the structures of RnQV1 virion
      strains W1075 and W1118. RnQV1 has a quadripartite genome, and the capsid is
      based on a single-shelled T=1 lattice built of P2-P4 dimers. Whereas the RnQV1
      W1118 capsid is built of full-length CP, P2 and P4 of RnQV1-W1075 are cleaved
      into several polypeptides, maintaining the capsid structural organization. RnQV1
      heterodimers have a quaternary organization similar to that of homodimers of
      reoviruses and other dsRNA mycoviruses. The RnQV1 capsid is the first T=1 capsid
      with a heterodimer as an asymmetric unit reported to date and follows the
      architectural principle for dsRNA viruses that a 120-subunit capsid is a
      conserved assembly that supports dsRNA replication and organization. IMPORTANCE:
      Given their importance to health, members of the family Reoviridae are the basis
      of most structural and functional studies and provide much of our knowledge of
      dsRNA viruses. Analysis of bacterial, protozoal, and fungal dsRNA viruses has
      improved our understanding of their structure, function, and evolution, as well.
      Here, we studied a dsRNA virus that infects the fungus Rosellinia necatrix, an
      ascomycete that is pathogenic to a wide range of plants. Using three-dimensional
      cryo-electron microscopy and analytical ultracentrifugation analysis, we
      determined the structure and stoichiometry of Rosellinia necatrix quadrivirus 1
      (RnQV1). The RnQV1 capsid is a T=1 capsid with 60 heterodimers as the asymmetric
      units. The large amount of genetic information used by RnQV1 to construct a
      simple T=1 capsid is probably related to the numerous virus-host and virus-virus
      interactions that it must face in its life cycle, which lacks an extracellular
      phase.

PMID- 27707924
TI  - The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact
      Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies.
AB  - : The glycoprotein of Ebola virus (EBOV GP), a member of the family Filoviridae,
      facilitates viral entry into target cells. In addition, EBOV GP antagonizes the
      antiviral activity of the host cell protein tetherin, which may otherwise
      restrict EBOV release from infected cells. However, it is unclear how EBOV GP
      antagonizes tetherin, and it is unknown whether the GP of Lloviu virus (LLOV), a
      filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here,
      we show that LLOV GP antagonizes tetherin, indicating that tetherin may not
      impede LLOV spread in human cells. Moreover, we demonstrate that appropriate
      processing of N-glycans in tetherin/GP-coexpressing cells is required for
      tetherin counteraction by EBOV GP. Furthermore, we show that an intact receptor
      binding domain (RBD) in the GP1 subunit of EBOV GP is a prerequisite for tetherin
      counteraction. In contrast, blockade of Niemann-Pick disease type C1 (NPC1), a
      cellular binding partner of the RBD, did not interfere with tetherin antagonism.
      Finally, we provide evidence that an antibody directed against GP1, which
      protects mice from a lethal EBOV challenge, may block GP-dependent tetherin
      antagonism. Our data, in conjunction with previous reports, indicate that
      tetherin antagonism is conserved among the GPs of all known filoviruses and
      demonstrate that the GP1 subunit of EBOV GP plays a central role in tetherin
      antagonism. IMPORTANCE: Filoviruses are reemerging pathogens that constitute a
      public health threat. Understanding how Ebola virus (EBOV), a highly pathogenic
      filovirus responsible for the 2013-2016 Ebola virus disease epidemic in western
      Africa, counteracts antiviral effectors of the innate immune system might help to
      define novel targets for antiviral intervention. Similarly, determining whether
      Lloviu virus (LLOV), a filovirus detected in bats in northern Spain, is inhibited
      by innate antiviral effectors in human cells might help to determine whether the
      virus constitutes a threat to humans. The present study shows that LLOV, like
      EBOV, counteracts the antiviral effector protein tetherin via its glycoprotein
      (GP), suggesting that tetherin does not pose a defense against LLOV spread in
      humans. Moreover, our work identifies the GP1 subunit of EBOV GP, in particular
      an intact receptor-binding domain, as critical for tetherin counteraction and
      provides evidence that antibodies directed against GP1 can interfere with
      tetherin counteraction.

PMID- 27707926
TI  - Repression of the Chromatin-Tethering Domain of Murine Leukemia Virus p12.
AB  - : Murine leukemia virus (MLV) p12, encoded within Gag, binds the viral
      preintegration complex (PIC) to the mitotic chromatin. This acts to anchor the
      viral PIC in the nucleus as the nuclear envelope re-forms postmitosis. Mutations
      within the p12 C terminus (p12 PM13 to PM15) block early stages in viral
      replication. Within the p12 PM13 region (p12 60PSPMA65), our studies indicated
      that chromatin tethering was not detected when the wild-type (WT) p12 protein
      (M63) was expressed as a green fluorescent protein (GFP) fusion; however,
      constructs bearing p12-I63 were tethered. N-terminal truncations of the activated
      p12-I63-GFP indicated that tethering increased further upon deletion of p12
      25DLLTEDPPPY34, which includes the late domain required for viral assembly. The
      p12 PM15 sequence (p12 70RREPP74) is critical for wild-type viral viability;
      however, virions bearing the PM15 mutation (p12 70AAAAA74) with a second M63I
      mutant were viable, with a titer 18-fold lower than that of the WT. The p12 M63I
      mutation amplified chromatin tethering and compensated for the loss of chromatin
      binding of p12 PM15. Rescue of the p12-M63-PM15 nonviable mutant with prototype
      foamy virus (PFV) and Kaposi's sarcoma herpesvirus (KSHV) tethering sequences
      confirmed the function of p1270-74 in chromatin binding. Minimally, full-strength
      tethering was seen with only p12 61SPIASRLRGRR71 fused to GFP. These results
      indicate that the p12 C terminus alone is sufficient for chromatin binding and
      that the presence of the p12 25DLLTEDPPPY34 motif in the N terminus suppresses
      the ability to tether. IMPORTANCE: This study defines a regulatory mechanism
      controlling the differential roles of the MLV p12 protein in early and late
      replication. During viral assembly and egress, the late domain within the p12 N
      terminus functions to bind host vesicle release factors. During viral entry, the
      C terminus of p12 is required for tethering to host mitotic chromosomes. Our
      studies indicate that the p12 domain including the PPPY late sequence temporally
      represses the p12 chromatin tethering motif. Maximal p12 tethering was identified
      with only an 11-amino-acid minimal chromatin tethering motif encoded at p1261-71
      Within this region, the p12-M63I substitution switches p12 into a tethering
      competent state, partially rescuing the p12-PM15 tethering mutant. A model for
      how this conformational change regulates early versus late functions is
      presented.

PMID- 27707925
TI  - HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an
      Infected Individual.
AB  - : The HIV envelope glycoprotein (Env) is extensively modified with host-derived N
      linked glycans. The high density of glycosylation on the viral spike limits
      enzymatic processing, resulting in numerous underprocessed oligomannose-type
      glycans. This extensive glycosylation not only shields conserved regions of the
      protein from the immune system but also acts as a target for anti-HIV broadly
      neutralizing antibodies (bnAbs). In response to the host immune system, the HIV
      glycan shield is constantly evolving through mutations affecting both the
      positions and numbers of potential N-linked glycosylation sites (PNGSs). Here,
      using longitudinal Env sequences from a clade C-infected individual (CAP256), we
      measured the impact of the shifting glycan shield during HIV infection on the
      abundance of oligomannose-type glycans. By analyzing the intrinsic mannose patch
      from a panel of recombinant CAP256 gp120s displaying high protein sequence
      variability and changes in PNGS number and positioning, we show that the
      intrinsic mannose patch persists throughout the course of HIV infection and
      correlates with the number of PNGSs. This effect of the glycan density on the
      processing state was also supported by the analysis of a cross-clade panel of
      recombinant gp120 glycoproteins. Together, these observations underscore the
      importance of glycan clustering for the generation of carbohydrate epitopes for
      anti-HIV bnAbs. The persistence of the intrinsic mannose patch over the course of
      HIV infection further highlights this epitope as an important target for HIV
      vaccine strategies. IMPORTANCE: Development of an HIV vaccine is critical for
      control of the HIV pandemic, and elicitation of broadly neutralizing antibodies
      (bnAbs) is likely to be a key component of a successful vaccine response. The HIV
      envelope glycoprotein (Env) is covered in an array of host-derived N-linked
      glycans often referred to as the glycan shield. This glycan shield is a target
      for many of the recently isolated anti-HIV bnAbs and is therefore under constant
      pressure from the host immune system, leading to changes in both glycan site
      frequency and location. This study aimed to determine whether these genetic
      changes impacted the eventual processing of glycans on the HIV Env and the
      susceptibility of the virus to neutralization. We show that despite this
      variation in glycan site positioning and frequency over the course of HIV
      infection, the mannose patch is a conserved feature throughout, making it a
      stable target for HIV vaccine design.

PMID- 27707927
TI  - TMPRSS12 Is an Activating Protease for Subtype B Avian Metapneumovirus.
AB  - : The entry of avian metapneumovirus (aMPV) into host cells initially requires
      the fusion of viral and cell membranes, which is exclusively mediated by fusion
      (F) protein. Proteolysis of aMPV F protein by endogenous proteases of host cells
      allows F protein to induce membrane fusion; however, these proteases have not
      been identified. Here, we provide the first evidence that the transmembrane
      serine protease TMPRSS12 facilitates the cleavage of subtype B aMPV (aMPV/B) F
      protein. We found that overexpression of TMPRSS12 enhanced aMPV/B F protein
      cleavage, F protein fusogenicity, and viral replication. Subsequently, knockdown
      of TMPRSS12 with specific small interfering RNAs (siRNAs) reduced aMPV/B F
      protein cleavage, F protein fusogenicity, and viral replication. We also found a
      cleavage motif in the aMPV/B F protein (amino acids 100 and 101) that was
      recognized by TMPRSS12. The histidine, aspartic acid, and serine residue (HDS)
      triad of TMPRSS12 was shown to be essential for the proteolysis of aMPV/B F
      protein via mutation analysis. Notably, we observed TMPRSS12 mRNA expression in
      target organs of aMPV/B in chickens. Overall, our results indicate that TMPRSS12
      is crucial for aMPV/B F protein proteolysis and aMPV/B infectivity and that
      TMPRSS12 may serve as a target for novel therapeutics and prophylactics for aMPV.
      IMPORTANCE: Proteolysis of the aMPV F protein is a prerequisite for F protein
      mediated membrane fusion of virus and cell and for aMPV infection; however, the
      proteases used in vitro and vivo are not clear. A combination of analyses,
      including overexpression, knockdown, and mutation methods, demonstrated that the
      transmembrane serine protease TMPRSS12 facilitated cleavage of subtype B aMPV
      (aMPV/B) F protein. Importantly, we located the motif in the aMPV/B F protein
      recognized by TMPRSS12 and the catalytic triad in TMPRSS12 that facilitated
      proteolysis of the aMPV/B F protein. This is the first report on TMPRSS12 as a
      protease for proteolysis of viral envelope glycoproteins. Our study will shed
      light on the mechanism of proteolysis of aMPV F protein and pathogenesis of aMPV.

PMID- 27707929
TI  - Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early
      Infection Block to Human Influenza Viruses.
AB  - : A role for pulmonary endothelial cells in the orchestration of cytokine
      production and leukocyte recruitment during influenza virus infection, leading to
      severe lung damage, has been recently identified. As the mechanistic pathway for
      this ability is not fully known, we extended previous studies on influenza virus
      tropism in cultured human pulmonary endothelial cells. We found that a subset of
      avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2
      viruses, could infect human pulmonary endothelial cells (HULEC) with high
      efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza
      viruses were capable of binding to host cellular receptors, becoming internalized
      and initiating hemifusion but failing to uncoat the viral nucleocapsid and to
      replicate in host nuclei. Unlike numerous cell types, including epithelial cells,
      we found that pulmonary endothelial cells constitutively express a high level of
      the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by
      small interfering RNA (siRNA) could partially rescue H1N1 virus infection in
      HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus
      infection in endothelial cells. In contrast, selected avian influenza viruses
      were able to escape IFITM3 restriction in endothelial cells, possibly by fusing
      in early endosomes at higher pH or by other, unknown mechanisms. Collectively,
      our study demonstrates that the human pulmonary endothelium possesses intrinsic
      immunity to human influenza viruses, in part due to the constitutive expression
      of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to
      escape this restriction, possibly contributing to virus-induced pneumonia and
      severe lung disease in humans. IMPORTANCE: Avian influenza viruses, including
      H5N1 and H7N9, have been associated with severe respiratory disease and fatal
      outcomes in humans. Although acute respiratory distress syndrome (ARDS) and
      progressive pulmonary endothelial damage are known to be present during severe
      human infections, the role of pulmonary endothelial cells in the pathogenesis of
      avian influenza virus infections is largely unknown. By comparing human seasonal
      influenza strains to avian influenza viruses, we provide greater insight into the
      interaction of influenza virus with human pulmonary endothelial cells. We show
      that human influenza virus infection is blocked during the early stages of virus
      entry, which is likely due to the relatively high expression of the host
      antiviral factors IFITMs (interferon-induced transmembrane proteins) located in
      membrane-bound compartments inside cells. Overall, this study provides a
      mechanism by which human endothelial cells limit replication of human influenza
      virus strains, whereas avian influenza viruses overcome these restriction factors
      in this cell type.

PMID- 27707928
TI  - Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients
      from India.
AB  - : Epidemiological studies suggest that India has the largest number of dengue
      virus infection cases worldwide. However, there is minimal information about the
      immunological responses in these patients. CD8 T cells are important in dengue,
      because they have been implicated in both protection and immunopathology. Here,
      we provide a detailed analysis of HLA-DR+ CD38+ and HLA-DR- CD38+ effector CD8 T
      cell subsets in dengue patients from India and Thailand. Both CD8 T cell subsets
      expanded and expressed markers indicative of antigen-driven proliferation, tissue
      homing, and cytotoxic effector functions, with the HLA-DR+ CD38+ subset being the
      most striking in these effector qualities. The breadth of the dengue-specific CD8
      T cell response was diverse, with NS3-specific cells being the most dominant.
      Interestingly, only a small fraction of these activated effector CD8 T cells
      produced gamma interferon (IFN-gamma) when stimulated with dengue virus peptide
      pools. Transcriptomics revealed downregulation of key molecules involved in T
      cell receptor (TCR) signaling. Consistent with this, the majority of these CD8 T
      cells remained IFN-gamma unresponsive even after TCR-dependent polyclonal
      stimulation (anti-CD3 plus anti-CD28) but produced IFN-gamma by TCR-independent
      polyclonal stimulation (phorbol 12-myristate 13-acetate [PMA] plus ionomycin).
      Thus, the vast majority of these proliferating, highly differentiated effector
      CD8 T cells probably acquire TCR refractoriness at the time the patient is
      experiencing febrile illness that leads to IFN-gamma unresponsiveness. Our
      studies open novel avenues for understanding the mechanisms that fine-tune the
      balance between CD8 T cell-mediated protective versus pathological effects in
      dengue. IMPORTANCE: Dengue is becoming a global public health concern. Although
      CD8 T cells have been implicated both in protection and in the cytokine-mediated
      immunopathology of dengue, how the balance is maintained between these opposing
      functions remains unknown. We comprehensively characterized CD8 T cell subsets in
      dengue patients from India and Thailand and show that these cells expand
      massively and express phenotypes indicative of overwhelming antigenic stimulus
      and tissue homing/cytotoxic-effector functions but that a vast majority of them
      fail to produce IFN-gamma in vitro Interestingly, the cells were fully capable of
      producing the cytokine when stimulated in a T cell receptor (TCR)-independent
      manner but failed to do so in TCR-dependent stimulation. These results, together
      with transcriptomics, revealed that the vast majority of these CD8 T cells from
      dengue patients become cytokine unresponsive due to TCR signaling
      insufficiencies. These observations open novel avenues for understanding the
      mechanisms that fine-tune the balance between CD8-mediated protective versus
      pathological effects.

PMID- 27707930
TI  - Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue
      Virus Infection.
AB  - Half of the world's population is exposed to the risk of dengue virus infection.
      Although a vaccine for dengue virus is now available in a few countries, its
      reported overall efficacy of about 60% is not ideal. Protective immune correlates
      following natural dengue virus infection remain undefined, which makes it
      difficult to predict the efficacy of new vaccines. In this study, we address the
      protective capacity of dengue virus-specific antibodies that are produced by
      plasmablasts a few days after natural secondary infection. Among a panel of 18
      dengue virus-reactive human monoclonal antibodies, four groups of antibodies were
      identified based on their binding properties. While antibodies targeting the
      fusion loop of the glycoprotein of dengue virus dominated the antibody response,
      two smaller groups of antibodies bound to previously undescribed epitopes in
      domain II of the E protein. The latter, largely serotype-cross-reactive
      antibodies, demonstrated increased stability of binding at pH 5. These antibodies
      possessed weak to moderate neutralization capacity in vitro but were the most
      efficacious in promoting the survival of infected mice. Our data suggest that the
      cross-reactive anamnestic antibody response has a protective capacity despite
      moderate neutralization in vitro and a moderate decrease of viremia in vivo
      IMPORTANCE: Antibodies can protect from symptomatic dengue virus infection.
      However, it is not easy to assess which classes of antibodies provide protection
      because in vitro assays are not always predictive of in vivo protection. During a
      repeat infection, dengue virus-specific immune memory cells are reactivated and
      large amounts of antibodies are produced. By studying antibodies cloned from
      patients with heterologous secondary infection, we tested the protective value of
      the serotype-cross-reactive "recall" or "anamnestic" response. We found that
      results from in vitro neutralization assays did not always correlate with the
      ability of the antibodies to reduce viremia in a mouse model. In addition, a
      decrease of viremia in mice did not necessarily improve survival. The most
      protective antibodies were stable at pH 5, suggesting that antibody binding in
      the endosomes, after the antibody-virus complex is internalized, might be
      important to block virus spread in the organism.

PMID- 27707931
TI  - Phosphorylation Requirement of Murine Leukemia Virus p12.
AB  - : The p12 protein of murine leukemia virus (MLV) Gag is associated with the
      preintegration complex (PIC), and mutants of p12 (PM14) exhibit defects in
      nuclear entry/retention. Mutants of the phosphorylated serine 61 also have been
      reported to have defects in the early life cycle. Here we show that a
      phosphorylated peptide motif derived from human papillomavirus 8 (HPV-8), the E2
      hinge region including residues 240 to 255, can functionally replace the main
      phosphorylated motif of MLV p12 and can rescue the viral titer of a strain with
      the lethal p12-PM14 mutation. Complementation with the HPV-8 E2 hinge motif
      generated multiple second-site mutations in live viral passage assays. Additional
      p12 phosphorylation sites were detected, including the late domain of p12 (PPPY)
      as well as the late domain/protease cleavage site of matrix (LYPAL), by mass
      spectrometry and Western blotting. Chromatin binding of p12-green fluorescent
      protein (GFP) fusion protein and functional complementation of p12-PM14 occurred
      in a manner independent of the E2 hinge region phosphorylation. Replacement of
      serine 61 by alanine within the minimal tethering domain (61SPMASRLRGRR71)
      maintained tethering, but in the context of the full-length p12, mutants with
      substitutions in S61 remained untethered and lost infectivity, indicating
      phosphorylation of p12 serine 61 functions to temporally regulate early and late
      p12 functions. IMPORTANCE: The p12 protein, required for both early and late
      viral functions, is the predominant phosphorylated viral protein of Moloney MLV
      and is required for virus viability. Our studies indicate that the N terminus of
      p12 represses the early function of the chromatin binding domain and that
      deletion of the N terminus activates chromatin binding in the wild-type Moloney
      MLV p12 protein. Mass spectrometry and mutagenesis studies suggest that
      phosphorylation of both the repression domain and the chromatin binding domain
      acts to temporally regulate this process at the appropriate stages during
      infection.

PMID- 27707933
TI  - Batterer Intervention Programs in Spain: An Analysis of Their Effectiveness.
AB  - Intimate partner violence against women is a social and women's health concern.
      Much effort has gone into providing services and support for victims of this
      violence. By contrast, intervention programs focusing on the batterers themselves
      have received far less attention. The purpose of this article is to provide a
      systematic review of the evidence regarding the effectiveness of batterer
      intervention programs (BIPs) implemented in Spain as provided by research
      published in peer-reviewed journals and scientific reports. The results obtained
      show that assessment focuses mainly on evaluating whether there is an improvement
      in the psychological variables of abusers. In cases where the rate of success or
      failure is analyzed, it is important to note the high drop-out rates observed,
      and the wide variability in success and improvement rates obtained. In summary,
      the results obtained in this revision allow to corroborate the assumption that
      associated with BIP is a lot of controversy, since its construction, its
      implementation, its assessment, and its effectiveness.

PMID- 27707934
TI  - Beyond the Walls: The Social Reintegration of Prisoners Through the Dialogic
      Reading of Classic Universal Literature in Prison.
AB  - This study analyzed whether it was possible to successfully transfer an
      experience of dialogic literary gatherings (DLGs) developed in a prison in the
      Basque Country (Spain), which was found to enhance the participants' readiness to
      return to their communities. A case study was conducted in a different prison in
      Catalonia that comprised interviews and focus groups with a group of female
      prisoners and volunteers involved in the DLG. The communicative analysis
      conducted showed that the replication of the DLG allowed the participants to
      discuss and reflect on their biographies and their expected pathways upon
      release, thus opening possibilities for personal and social change. The results
      show that participants perceived the DLG as a helpful resource for social
      reintegration and suggest that DLGs can be transferred to different correctional
      institutions.

PMID- 27707932
TI  - Deep Sequencing of Influenza A Virus from a Human Challenge Study Reveals a
      Selective Bottleneck and Only Limited Intrahost Genetic Diversification.
AB  - : Knowledge of influenza virus evolution at the point of transmission and at the
      intrahost level remains limited, particularly for human hosts. Here, we analyze a
      unique viral data set of next-generation sequencing (NGS) samples generated from
      a human influenza challenge study wherein 17 healthy subjects were inoculated
      with cell- and egg-passaged virus. Nasal wash samples collected from 7 of these
      subjects were successfully deep sequenced. From these, we characterized changes
      in the subjects' viral populations during infection and identified differences
      between the virus in these samples and the viral stock used to inoculate the
      subjects. We first calculated pairwise genetic distances between the subjects'
      nasal wash samples, the viral stock, and the influenza virus A/Wisconsin/67/2005
      (H3N2) reference strain used to generate the stock virus. These distances
      revealed that considerable viral evolution occurred at various points in the
      human challenge study. Further quantitative analyses indicated that (i) the viral
      stock contained genetic variants that originated and likely were selected for
      during the passaging process, (ii) direct intranasal inoculation with the viral
      stock resulted in a selective bottleneck that reduced nonsynonymous genetic
      diversity in the viral hemagglutinin and nucleoprotein, and (iii) intrahost viral
      evolution continued over the course of infection. These intrahost evolutionary
      dynamics were dominated by purifying selection. Our findings indicate that rapid
      viral evolution can occur during acute influenza infection in otherwise healthy
      human hosts when the founding population size of the virus is large, as is the
      case with direct intranasal inoculation. IMPORTANCE: Influenza viruses
      circulating among humans are known to rapidly evolve over time. However, little
      is known about how influenza virus evolves across single transmission events and
      over the course of a single infection. To address these issues, we analyze
      influenza virus sequences from a human challenge experiment that initiated
      infection with a cell- and egg-passaged viral stock, which appeared to have
      adapted during its preparation. We find that the subjects' viral populations
      differ genetically from the viral stock, with subjects' viral populations having
      lower representation of the amino-acid-changing variants that arose during viral
      preparation. We also find that most of the viral evolution occurring over single
      infections is characterized by further decreases in the frequencies of these
      amino-acid-changing variants and that only limited intrahost genetic
      diversification through new mutations is apparent. Our findings indicate that
      influenza virus populations can undergo rapid genetic changes during acute human
      infections.

PMID- 27707935
TI  - How Does It Work? Mechanisms of Action in an In-Prison Restorative Justice
      Program.
AB  - Research is limited on mechanisms of action in restorative justice interventions.
      This multimethods study delineates the change processes underlying a successful
      in-prison group treatment program by (a) examining shifts in offenders' self
      schemas and (b) identifying key program components that influence this movement.
      Researchers assigned to small groups as "co-facilitators" gathered data using
      participant observation, semi-structured interviews, and psychological
      assessments at three time points. Mechanisms of action include group norms and
      behaviors that contrast with prior experiences and uncover offenders' self
      schemas through intrapsychic processes, which prompt them to test and act upon
      new possible selves through the group process.

PMID- 27707936
TI  - Liver glucose metabolism in humans.
AB  - Information about normal hepatic glucose metabolism may help to understand
      pathogenic mechanisms underlying obesity and diabetes mellitus. In addition,
      liver glucose metabolism is involved in glycosylation reactions and connected
      with fatty acid metabolism. The liver receives dietary carbohydrates directly
      from the intestine via the portal vein. Glucokinase phosphorylates glucose to
      glucose 6-phosphate inside the hepatocyte, ensuring that an adequate flow of
      glucose enters the cell to be metabolized. Glucose 6-phosphate may proceed to
      several metabolic pathways. During the post-prandial period, most glucose 6
      phosphate is used to synthesize glycogen via the formation of glucose 1-phosphate
      and UDP-glucose. Minor amounts of UDP-glucose are used to form UDP-glucuronate
      and UDP-galactose, which are donors of monosaccharide units used in
      glycosylation. A second pathway of glucose 6-phosphate metabolism is the
      formation of fructose 6-phosphate, which may either start the hexosamine pathway
      to produce UDP-N-acetylglucosamine or follow the glycolytic pathway to generate
      pyruvate and then acetyl-CoA. Acetyl-CoA may enter the tricarboxylic acid (TCA)
      cycle to be oxidized or may be exported to the cytosol to synthesize fatty acids,
      when excess glucose is present within the hepatocyte. Finally, glucose 6
      phosphate may produce NADPH and ribose 5-phosphate through the pentose phosphate
      pathway. Glucose metabolism supplies intermediates for glycosylation, a post
      translational modification of proteins and lipids that modulates their activity.
      Congenital deficiency of phosphoglucomutase (PGM)-1 and PGM-3 is associated with
      impaired glycosylation. In addition to metabolize carbohydrates, the liver
      produces glucose to be used by other tissues, from glycogen breakdown or from de
      novo synthesis using primarily lactate and alanine (gluconeogenesis).

PMID- 27707937
TI  - Effects of porcine MyD88 knockdown on the expression of TLR4 pathway-related
      genes and proinflammatory cytokines.
AB  - As a critical adapter protein in Toll-like receptor (TLR)/Interleukin (IL)-1R
      signalling pathway, myeloid differentiation protein 88 (MyD88) plays an important
      role in immune responses and host defence against pathogens. The present study
      was designed to provide a foundation and an important reagent for the mechanistic
      study of MyD88 and its role TLR/IL-1R signalling pathways in porcine immunity.
      Lentivirus-mediated RNAi was used to generate a porcine PK15 cell line with a
      silenced MyD88 gene and quantitative real-time PCR (qPCR) and Western blotting
      were used to detect changes in the expression of critical genes in the Toll-like
      receptor 4 (TLR4) signalling pathway. ELISA was used to measure the levels of
      seven proinflammatory cytokines-interleukin-1beta (IL-1beta), tumour necrosis
      factor-alpha (TNF-alpha), IL-6, IL-8, IL-12, macrophage inflammatory protein
      (MIP)-1alpha and MIP-1beta-in cell culture supernatants after MyD88 silencing. We
      successfully obtained a PK15 cell line with 61% MyD88 mRNA transcript down
      regulated. In PK15 cells with MyD88 silencing, the transcript levels of TLR4 and
      IL-1beta were significantly reduced, whereas there were no significant changes in
      the expression levels of cluster of differentiation antigen 14 (CD14), interferon
      alpha (IFN-alpha) or TNF-alpha The ELISA results showed that the levels of most
      cytokines were not significantly changed apart from IL-8 without stimulation,
      which was significantly up-regulated. When cells were induced by
      lipopolysaccharide (LPS) (0.1 MUg/ml) for 6 h, the global level of seven
      proinflammatory cytokines up-regulated and the level of IL-1beta, TNF-alpha, IL
      6, IL-8 and IL-12 of Blank and negative control (NC) group up-regulated more
      significantly than RNAi group (P<0.05), which revealed that the MyD88 silencing
      could reduce the TLR4 signal transduction which inhibited the release of
      proinflammatory cytokines and finally leaded to immunosuppression.

PMID- 27707939
TI  - Comparative Genomic Analysis of Haemophilus haemolyticus and Nontypeable
      Haemophilus influenzae and a New Testing Scheme for Their Discrimination.
AB  - Haemophilus haemolyticus has been recently discovered to have the potential to
      cause invasive disease. It is closely related to nontypeable Haemophilus
      influenzae (NT H. influenzae). NT H. influenzae and H. haemolyticus are often
      misidentified because none of the existing tests targeting the known phenotypes
      of H. haemolyticus are able to specifically identify H. haemolyticus Through
      comparative genomic analysis of H. haemolyticus and NT H. influenzae, we
      identified genes unique to H. haemolyticus that can be used as targets for the
      identification of H. haemolyticus A real-time PCR targeting purT (encoding
      phosphoribosylglycinamide formyltransferase 2 in the purine synthesis pathway)
      was developed and evaluated. The lower limit of detection was 40 genomes/PCR; the
      sensitivity and specificity in detecting H. haemolyticus were 98.9% and 97%,
      respectively. To improve the discrimination of H. haemolyticus and NT H.
      influenzae, a testing scheme combining two targets (H. haemolyticus purT and H.
      influenzae hpd, encoding protein D lipoprotein) was also evaluated and showed
      96.7% sensitivity and 98.2% specificity for the identification of H. haemolyticus
      and 92.8% sensitivity and 100% specificity for the identification of H.
      influenzae, respectively. The dual-target testing scheme can be used for the
      diagnosis and surveillance of infection and disease caused by H. haemolyticus and
      NT H. influenzae.

PMID- 27707938
TI  - Development and Evaluation of a Molecular Diagnostic Method for Rapid Detection
      of Histoplasma capsulatum var. farciminosum, the Causative Agent of Epizootic
      Lymphangitis, in Equine Clinical Samples.
AB  - Histoplasma capsulatum var. farciminosum, the causative agent of epizootic
      lymphangitis (EZL), is endemic in parts of Africa. Diagnosis based on clinical
      signs and microscopy lacks specificity and is a barrier to further understanding
      this neglected disease. Here, a nested PCR method targeting the internal
      transcribed spacer (ITS) region of the rRNA operon was validated for application
      to equine clinical samples. Twenty-nine horses with signs of EZL from different
      climatic regions of Ethiopia were clinically examined. Blood samples and
      aspirates of pus from cutaneous nodules were taken, along with blood from a
      further 20 horses with no cutaneous EZL lesions. Among the 29 horses with
      suspected cases of EZL, H. capsulatum var. farciminosum was confirmed by
      extraction of DNA from pus and blood samples from 25 and 17 horses, respectively.
      Positive PCR results were also obtained with heat-inactivated pus (24 horses) and
      blood (23 horses) spotted onto Whatman FTA cards. Two positive results were
      obtained among blood samples from 20 horses that did not exhibit clinical signs
      of EZL. These are the first reports of the direct detection of H. capsulatum var.
      farciminosum in equine blood and at high frequency among horses exhibiting
      cutaneous lesions. The nested PCR outperformed conventional microscopic
      diagnosis, as characteristic yeast cells could be observed only in 14 pus
      samples. The presence of H. capsulatum var. farciminosum DNA was confirmed by
      sequencing the cloned PCR products, and while alignment of the ITS amplicons
      showed very little sequence variation, there was preliminary single nucleotide
      polymorphism-based evidence for the existence of two subgroups of H. capsulatum
      var. farciminosum This molecular diagnostic method now permits investigation of
      the epidemiology of EZL.

PMID- 27707940
TI  - Chlorhexidine versus Tincture of Iodine for Reduction of Blood Culture
      Contamination Rates: a Prospective Randomized Crossover Study.
AB  - Blood cultures (BCs) are the standard method for diagnosis of bloodstream
      infections (BSIs). However, the average BC contamination rate (CR) in U.S.
      hospitals is 2.9%, potentially resulting in unnecessary antibiotic use and
      excessive therapy costs. Several studies have compared various skin antisepsis
      agents without a clear consensus as to which agent is most effective in reducing
      contamination. A prospective, randomized crossover study directly comparing blood
      culture contamination rates using chlorhexidine versus iodine tincture for skin
      antisepsis was performed at Robert Wood Johnson University Hospital (RWJUH).
      Eight nursing units at RWJUH were provided with blood culture kits containing
      either chlorhexidine (CH) or iodine tincture (IT) for skin antisepsis prior to
      all blood culture venipunctures, which were obtained by nurses or clinical care
      technicians. At quarterly intervals, the antiseptic agent used on each nursing
      unit was switched. Analyses of positive BCs were performed to distinguish true
      BSIs from contaminants. Of the 6,095 total BC sets obtained from the
      participating nursing units, 667 (10.94%) were positive and 238 (3.90%) were
      judged by the investigators to be contaminated. Of the 3,130 BCs obtained using
      IT, 340 (10.86%) were positive and 123 (3.93%) were contaminated. Of 2,965 BCs
      obtained using CH, 327 (11.03%) were positive and 115 (3.88%) were contaminated.
      The rates of contaminated BCs were not statistically significant between the two
      antiseptic agents (P = 1.0). We conclude that CH and IT are equivalent agents for
      blood culture skin antisepsis.

PMID- 27707941
TI  - Development of a Colloidal Gold-Based Immunochromatographic Strip for Rapid
      Detection of Klebsiella pneumoniae Serotypes K1 and K2.
AB  - In this study, a novel colloidal gold-based immunochromatographic strip (ICS)
      containing anti-Klebsiella pneumoniae capsular polysaccharide polyclonal
      antibodies was developed to specifically detect K. pneumoniae serotypes K1 and
      K2. Capsular polysaccharide K1 and K2 antigens were first used to produce
      polyclonal anti-K1 and anti-K2 antibodies. Reference strains with different
      serotypes, nontypeable K. pneumoniae strains, and other bacterial species were
      then used to assess the sensitivity and specificity of these test strips. The
      detection limit was found to be 105 CFU, and the ICSs were stable for 6 months
      when stored at room temperature. No false-positive or false-negative results were
      observed, and equivalent results were obtained compared to those of more
      conventional test methods, such as PCR or serum agglutination. In conclusion, the
      ICS developed here requires no technical expertise and allows for the specific,
      rapid, and simultaneous detection of K. pneumoniae serotypes K1 and K2.

PMID- 27707942
TI  - Screening for Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus,
      and Treponema pallidum by Blood Testing Using a Bio-Flash Technology-Based
      Algorithm before Gastrointestinal Endoscopy.
AB  - Currently, conventional enzyme immunoassays which use manual gold immunoassays
      and colloidal tests (GICTs) are used as screening tools to detect Treponema
      pallidum (syphilis), hepatitis B virus (HBV), hepatitis C virus (HCV), human
      immunodeficiency virus type 1 (HIV-1), and HIV-2 in patients undergoing surgery.
      The present observational, cross-sectional study compared the sensitivity,
      specificity, and work flow characteristics of the conventional algorithm with
      manual GICTs with those of a newly proposed algorithm that uses the automated Bio
      Flash technology as a screening tool in patients undergoing gastrointestinal (GI)
      endoscopy. A total of 956 patients were examined for the presence of serological
      markers of infection with HIV-1/2, HCV, HBV, and T. pallidum The proposed
      algorithm with the Bio-Flash technology was superior for the detection of all
      markers (100.0% sensitivity and specificity for detection of anti-HIV and anti
      HCV antibodies, HBV surface antigen [HBsAg], and T. pallidum) compared with the
      conventional algorithm based on the manual method (80.0% sensitivity and 98.6%
      specificity for the detection of anti-HIV, 75.0% sensitivity for the detection of
      anti-HCV, 94.7% sensitivity for the detection of HBsAg, and 100% specificity for
      the detection of anti-HCV and HBsAg) in these patients. The automated Bio-Flash
      technology-based screening algorithm also reduced the operation time by 85.0%
      (205 min) per day, saving up to 24 h/week. In conclusion, the use of the newly
      proposed screening algorithm based on the automated Bio-Flash technology can
      provide an advantage over the use of conventional algorithms based on manual
      methods for screening for HIV, HBV, HCV, and syphilis before GI endoscopy.

PMID- 27707944
TI  - Laboratory Evaluation of Two Commercial Abamectin-Based Insecticides Against
      Anastrepha ludens (Diptera: Tephritidae): Lethal and Sublethal Effects.
AB  - Toxic environmental effects of most insecticides have led to a search for bio
      organic insecticides. In this study, we tested the effects of lethal and
      sublethal exposure to two abamectin-based insecticides (VOLIAM TARGO and LUQ
      THOR) on survival, mating, and oviposition of the tephritid Anastrepha ludens
      (Loew). Different doses of insecticides (0.001-2.00% of the commercial products)
      were offered mixed with the phagostimulant bait Captor commonly used in spraying
      and in trapping activities for the control of flies. Both insecticides exhibited
      90% killing effectiveness (Abbott index) when offered in doses between 0.02 to
      2.00%. The LC50 obtained from the bioassay at 72 h after treatment was 0.003% of
      commercial product for TARGO and 0.008% for LUQ-THOR. Sublethal exposures to
      insecticides (0.003%; LC50 for TARGO and LC30 for LUQ-THOR) caused a reduction in
      oviposition but not in mating parameters, indicating that females were more
      susceptible than males to reduced doses of insecticide. The mean amount of eggs
      deposited 5 d after feeding on the insecticide-bait mixtures was reduced up to a
      third compared with the amount of eggs deposited by untreated females. Both
      insecticides are promising bio-organic alternatives to malathion in bait control
      programs against A. ludens.

PMID- 27707943
TI  - Action observation training of community ambulation for improving walking ability
      of patients with post-stroke hemiparesis: a randomized controlled pilot trial.
AB  - PURPOSE: To investigate the effects of action observation training involving
      community-based ambulation for improving walking ability after stroke. DESIGN:
      Randomized, controlled pilot study. SETTING: Inpatient rehabilitation hospital.
      SUBJECTS: A total of 25 inpatients with post-stroke hemiparesis were randomly
      assigned to either the experimental group ( n = 12) or control group ( n = 13).
      INTERVENTION: Subjects of the experimental group watched video clips
      demonstrating four-staged ambulation training with a more complex environment
      factor for 30 minutes, three times a week for four weeks. Meanwhile, subjects of
      the control group watched video clips, which showed different landscape pictures.
      MAIN MEASURES: Walking function was evaluated before and after the four-week
      intervention using a 10-m walk test, community walk test, activities-specific
      balance confidence scale, and spatiotemporal gait measures. RESULTS: Changes in
      the values for the 10-m walk test (0.17 +/-0.19 m/s vs. 0.05 +/-0.08 m/s),
      community walk test (-151.42 +/-123.82 seconds vs. 67.08 +/-176.77 seconds), and
      activities-specific balance confidence (6.25 +/-5.61 scores vs. 0.72 +/-2.24
      scores) and the spatiotemporal parameters (i.e. stride length (19.00 +/-11.34 cm
      vs. 3.16 +/-11.20 cm), single support (5.87 +/-5.13% vs. 0.25 +/-5.95%), and
      velocity (15.66 +/-12.34 cm/s vs. 2.96 +/-10.54 cm/s)) indicated a significant
      improvement in the experimental group compared with the control group. In the
      experimental group, walking function and ambulation confidence was significantly
      different between the pre- and post-intervention, whereas the control group
      showed a significant difference only in the 10-m walk test. CONCLUSIONS: Action
      observation training of community ambulation may be favorably used for improving
      walking function of patients with post-stroke hemiparesis.

PMID- 27707945
TI  - Disrupting Mating Behavior of Diaphorina citri (Liviidae).
AB  - Severe economic damage from citrus greening disease, caused by 'Candidatus
      Liberibacter asiaticus' bacteria, has stimulated development of methods to reduce
      mating and reproduction in populations of its insect vector, Diaphorina citri
      (Hemiptera: Liviidae). Male D. citri find mating partners by walking on host
      plants, intermittently producing vibrational calls that stimulate duetting
      replies by receptive females. The replies provide orientational feedback,
      assisting the search process. To test a hypothesis that D. citri mating can be
      disrupted using vibrational signals that compete with and/or mask female replies,
      courtship bioassays were conducted in citrus trees with or without interference
      from female reply mimics produced by a vibrating buzzer. Statistically
      significant reductions occurred in the rates and proportions of mating when the
      buzzer produced reply mimics within 0.4 s after male courtship calls compared
      with undisturbed controls. Observations of courtship behaviors in the two
      bioassays revealed activity patterns that likely contributed to the reductions.
      In both disruption and control tests, males reciprocated frequently between
      structural bifurcations and other transition points where signal amplitudes
      changed. Males in the disruption bioassay had to select among vibrational signals
      combined from the buzzer and the female at each transition point. They often
      turned towards the buzzer instead of the female. There was a statistically
      significant reduction in the proportion of males mating if they contacted the
      buzzer, possibly due to its higher vibration amplitude and duration in comparison
      with female replies. Potential applications of D. citri mating disruption
      technology in citrus groves are discussed.

PMID- 27707946
TI  - Impact of Citrus Thrips (Thysanoptera: Thripidae) on the Growth and Productivity
      of Southern Highbush Blueberries in California.
AB  - Citrus thrips, Scirtothrips citri (Moulton), is a foliage-feeding pest of
      blueberries in the San Joaquin Valley of California. We conducted a 4-yr field
      study to determine the type and amount of damage caused by this species. Using
      pesticides, we established gradients of citrus thrips in commercial blueberry
      fields near Richgrove, CA, in the fall of 2006, 2007, 2009, and 2014. Thrips
      densities were evaluated weekly for ~1 mo to determine cumulative thrips-days and
      correlate levels with the average length of new growth. During all four years of
      the study, there were significant negative correlations between thrips-days and
      shoot length (for every 100 thrips-days over a period of 4-5 wk there were
      reductions in the length of new shoot growth of 0.41 to 2.45 cm, 6.4-10.3%).
      During the spring following each trial, we evaluated the impact of thrips-days on
      blueberry yield and quality. During the 2006 trial, there was a significant
      negative correlation between thrips-days and yield as well as the number of
      berries per plant, but no yield effect was observed in the other three years of
      the study. No impacts on fruit quality were found any year. A discussion of the
      complexity of economic injury levels in blueberries is provided, especially
      considering that the cost of spraying for citrus thrips (estimated at US$150/ha)
      is almost irrelevant given crop values often in excess of US$100,000/ha.

PMID- 27707947
TI  - Residual and Systemic Efficacy of Chlorantraniliprole and Flubendiamide Against
      Corn Earworm (Lepidoptera: Noctuidae) in Soybean.
AB  - Experiments were conducted in Mississippi from 2013 to 2015 to determine the
      systemic and residual efficacy of chlorantraniliprole and flubendiamide against
      corn earworm, Helicoverpa zea (Boddie), in soybean. Both insecticides were
      applied at V4 and R3. Ten leaves that were present at the time of application and
      10 newly emerged leaves that were not present at the time of application were
      collected to measure residual and systemic efficacy, respectively. Ten pods were
      removed from each plot at R5.5. For all assays, corn earworm larvae were placed
      on plant material. Chlorantraniliprole appeared to provide systemic control of H.
      zea, but was dependent on soybean growth stage at the time of application. In the
      V4 experiment, chlorantraniliprole resulted in greater mortality than the control
      on new leaves at 7 d after treatment, but not at 14 d. In the R3 experiment,
      chlorantraniliprole resulted in greater than 90% mortality on new leaves at all
      evaluation intervals. Mortality of H. zea on new leaves was <17% for
      flubendiamide and was not different than the control. Both insecticides resulted
      in significant mortality of H. zea on leaves that were present at the time of
      application for at least 31 d after application. Chlorantraniliprole resulted in
      greater mortality than flubendiamide at 24 and 31 d. Neither insecticide resulted
      in mortality of H. zea feeding on reproductive structures. These results suggest
      that chlorantraniliprole moves to new vegetative structures but not to
      reproductive structures of soybean, and that flubendiamide does not move
      systemically.

PMID- 27707948
TI  - D2R2: an evidence-based decision support tool to aid prioritisation of animal
      health issues for government funding.
AB  - An evidence-based decision support tool, 'D2R2', has been developed by Defra. It
      contains a wide range of standardised information about exotic and endemic
      diseases held in 'disease profiles'. Each profile includes 40 criteria used for
      scoring, enabling D2R2 to provide relative priority rankings for every disease
      profiled. D2R2 also provides a range of reports for each disease and the
      functionality to explore the impact of changes in any criterion or weighting on a
      disease's ranking. These outputs aid the prioritisation and management of animal
      diseases by government. D2R2 was developed with wide stakeholder engagement and
      its design was guided by clear specifications. It uses the weighted scores of a
      limited number of criteria to generate impact and risk scores for each disease,
      and relies on evidence drawn from published material wherever possible and
      maintained up to date. It allows efficient use of expertise, as maintained
      disease profiles reduce the need for on call, reactive, expert input for policy
      development and enables rapid simultaneous access to the same information by
      multiple parties, for example during exotic disease outbreaks. The experience in
      developing D2R2 has been shared internationally to assist others with their
      development of disease prioritisation and categorisation systems.

PMID- 27707949
TI  - The physical health of Indigenous and non-Indigenous patients participating in
      residential rehabilitation programs: a comparison study.
AB  - OBJECTIVE: To examine the differences in the physical health of Indigenous and
      non-Indigenous patients with severe mental illness (SMI) undergoing psychiatric
      rehabilitation. METHODS: An audit of the physical health of patients ( n = 361)
      in all publicly funded residential rehabilitation programs in Queensland was
      carried out in late 2014. Data collection focused on clinical and lifestyle
      factors associated with physical health. RESULTS: The prevalence of smoking,
      substance use and type 2 diabetes in Indigenous patients was significantly higher
      than rates found in non-Indigenous patients. Metabolic syndrome was also
      significantly higher in indigenous patients, with 66% of Indigenous patients
      compared to 46% of non-Indigenous patients meeting criteria for metabolic
      syndrome. CONCLUSIONS: Patients with SMI in residential rehabilitation programs
      have poor physical health. Our findings underscore the need for clinicians to
      develop and evaluate interventions aimed at improving the metabolic profile of
      those with SMI in residential rehabilitation programs. Historical factors and
      cultural traditions need to be considered when designing lifestyle interventions
      for Indigenous patients.

PMID- 27707950
TI  - Chronic headache with medication overuse: Long-term prognosis after withdrawal
      therapy.
AB  - Background Knowledge about long-term outcomes after medication withdrawal therapy
      for chronic headache, including tension type and migraine headache is lacking.
      Methods We re-examined 56 patients an average of nine years after they
      participated in a medication withdrawal study with a one-year follow-up. We
      collected and compared data on headache, use of medication, quality of life,
      quality of sleep, anxiety, depression, and labor participation one and nine years
      after the start of withdrawal therapy. Results Headache days per month decreased
      from 16.7 (14.0-19.3) at one year to 13.3 (10.6-15.9) at nine years (P = 0.007).
      The proportion of patients meeting the criteria for chronic headache decreased
      from 27/56 (48%) at one year to 18/56 (32%) at nine years (P = 0.004). Medication
      overuse was reported in seven (13%) patients at one year and 18 (32%) at nine
      years (P = 0.013). The majority of patients overusing medication at nine years
      (10/18) belonged to a group of 14 patients who had a poor early response to
      withdrawal therapy and had sustained chronic headache after nine years. After
      excluding patients receiving retirement pensions, the proportion who received
      disability benefits increased from 21/55 (38%) at one year to 30/49 (61%) at nine
      years (P = 0.003). Conclusion Improvements after withdrawal therapy for chronic
      headache last at least nine years, with a parallel increase in the use of
      disability benefits. However, a high proportion of patients with a poor initial
      response to withdrawal therapy and sustained chronic headache overuse medication.

PMID- 27707951
TI  - Different processing of meningeal and cutaneous pain information in the spinal
      trigeminal nucleus caudalis.
AB  - Introduction Within superficial trigeminal nucleus caudalis (Sp5C) (laminae
      I/II), meningeal primary afferents project exclusively to lamina I, whereas
      nociceptive cutaneous ones distribute in both lamina I and outer lamina II.
      Whether such a relative absence of meningeal inputs to lamina II represents a
      fundamental difference from cutaneous pathways in the central processing of
      sensory information is still unknown. Methods We recorded extracellular field
      potentials in the superficial Sp5C of anesthetised rats evoked by electrically
      stimulating the dura mater, to selectively assess the synaptic transmission
      between meningeal primary afferents and second-order Sp5C neurons, the first
      synapse in trigeminovascular pathways. We tested the effect of systemic morphine
      and local glycinergic and GABAAergic disinhibition. Results Meningeal stimulation
      evokes two negative field potentials in superficial Sp5C. The conduction
      velocities of the activated primary afferents are within the Adelta- and C-fibre
      ranges. Systemic morphine specifically suppresses meningeal C-fibre-evoked field
      potentials, and this effect is reversed by systemic naloxone. Segmental
      glycinergic or GABAAergic disinhibition strongly potentiates meningeal C-fibre
      evoked field potentials but not Adelta-fibre ones. Interestingly, the same
      segmental disinhibition conversely potentiates cutaneous Adelta-fibre-evoked
      field potentials and suppresses C-fibre ones. Conclusion These findings reveal
      that the different anatomical organization of meningeal and cutaneous inputs into
      superficial Sp5C is associated with a different central processing of meningeal
      and cutaneous pain information within Sp5C. Moreover, they suggest that the
      potentiation upon local disinhibition of the first synapse in trigeminovascular
      pathways may contribute to the generation of headache pain.

PMID- 27707953
TI  - Erratum.

PMID- 27707952
TI  - Examining Chlamydia trachomatis and Neisseria gonorrhoeae rates between 2010 and
      2015: a population-based observational study.
AB  - Bacterial sexually transmitted infections including Chlamydia trachomatis and
      Neisseria gonorrhoeae remain an important public health concern. We aimed to
      assess the population-based incidence of C. trachomatis and N. gonorrhoeae in an
      age-standardized cohort over time. A retrospective study of a large Canadian
      health region was undertaken between 2010 and 2015 using linked census and
      digital laboratory data. C. trachomatis and N. gonorrhoeae tests were linked to
      patient data. Sex and age-standardized incidence rates (IR) and ratios (IRR) were
      calculated for cases and testing rates. The annual mean population was 1,150,556
      individuals (50.1% female). A total of 15,109 cases of chlamydia and 981 cases of
      gonorrhoea occurred. The overall IR for chlamydia ranged from 18.81 to 25.63
      cases per 10,000 person-years. The IRR was 1.27 (95% CI 1.20-1.34, p < 0.001) for
      the comparison of 2015 and 2010 rates. For gonorrhoea, overall rates ranged from
      0.92 to 1.86 cases per 10,000 person-years. The IRR for gonorrhoea was 2.02 (95%
      CI 1.56-2.59, p < 0.001) for 2015 and 2010 rates. In our large population-based
      study spanning six years, we observed increasing rates of C. trachomatis and N.
      gonorrhoeae with low testing rates.

PMID- 27707954
TI  - Late HIV presentation - missed opportunities and factors associated with a
      changing pattern over time.
AB  - Delayed diagnosis of HIV infection has negative clinical, economic and public
      health implications. The study primary aim was to identify factors associated
      with late HIV presentation (Late Presenters [LPS], CD4 cell count < 350
      cells/mm3). A secondary aim was to identify changing trends of late HIV
      presentation from 2002 to 2014 at our centre. A retrospective cohort study was
      performed. Demographic data and CD4 cell count of new HIV diagnoses presenting to
      our ambulatory HIV service over four time-periods from 2002 to 2014 were
      recorded. Proportion of LPS and factors associated with late presentation were
      compared using Graphpad Instat. In 2014, of 231 new patients attending for HIV
      care, 75 (32.6%) were late presenters versus 146 (66.4%) in 2002. This indicates
      a decreasing proportion of LPS from 2002 to 2014. However, the proportion of
      those with CD4 cell counts <200 on presentation at these two time intervals
      remain unchanged. The overall proportion of male LPS has increased over time and
      the proportion of LPS in the men who have sex with men (MSM) cohort has decreased
      over time, reflecting increased frequency of both HIV testing and diagnoses in
      MSM in recent years. The proportion of heterosexual LPS has not changed
      significantly in the same time period and LPS were older in 2014 versus 2002. The
      proportion of LPS defined by CD4 cell count remains higher than is justifiable in
      an era of increased HIV testing and awareness. Further targets for HIV testing to
      decrease rates of LPS include non-traditional risk groups including heterosexual
      and older patient cohorts. LPS rates are lower than rates found internationally,
      and it is possible that consensus definition of LPS needs to be revised.

PMID- 27707956
TI  - Dynamics of Base Excision Repair at the Maternal-Fetal Interface in Pregnancies
      Complicated by Preeclampsia.
AB  - Preeclampsia (PE) (gestational proteinuric hypertension) is the leading cause of
      maternal and perinatal mortality worldwide. Although placental endothelial
      dysfunction and oxidative stress are known to contribute to PE, the exact
      pathological basis for this disorder remains unclear. Previously, we demonstrated
      that DNA damage at the maternal-fetal interface is more common in the placentas
      of women with PE than normotensive controls. In this study, we utilized an in
      vivo comparative study, including 20 preeclamptic women and 8 healthy control
      subjects, and an in vitro hypoxia/reperfusion model to mimic the effects of
      oxidative stress at the maternal-fetal interface. We tracked the spatial pattern
      of expression of 2 base excision repair proteins, 8-oxoguanine glycosylase (OGG1)
      and apurinic/apyrimidinic endonuclease-1 (APE1), at the maternal-fetal interface
      in response to oxidative stress. In vivo, we found a significant increase in OGG1
      and APE1 concentrations in PE placental tissues as compared to normotensive
      controls ( P < .0001). Further, our in vitro study revealed that OGG1 and APE1
      expression is much greater in maternal cells (decidua) than in fetal cells
      (cytotrophoblasts) of placental tissue subjected to oxidative stress ( P <
      .0001). Our results suggest that OGG1 and APE1 likely protect decidual cells from
      oxidative base damage.

PMID- 27707955
TI  - Palliative long-term abdominal drains in refractory ascites due to end-stage
      liver disease: A case series.
AB  - BACKGROUND: Ascites, the commonest complication of cirrhosis, leads to frequent
      hospitalisations. Refractory ascites confers a median survival of 6 months
      without liver transplantation. In many, the management remains palliative (large
      volume paracentesis). Despite calls for improvement, palliative and end-of-life
      care is not yet integrated into end-stage liver disease. Long-term abdominal
      drains are a palliative strategy in malignant ascites, but not end-stage liver
      disease. CASE PRESENTATION: A retrospective, single centre, case series review
      was performed of patients undergoing long-term abdominal drain placement for
      refractory ascites secondary to end-stage liver disease at a large teaching
      hospital between August 2011 and March 2013. Case management: Patients with end
      stage liver disease and refractory ascites, where liver transplantation was not
      an option, were considered for long-term abdominal drains. Seven patients
      underwent successful long-term abdominal drain insertion after multi-professional
      assessment. Case outcome: Following long-term abdominal drain insertion, mean
      hospital attendances reduced to 1 (0-4) from 9 (4-21), with none for ascites
      management. Median survival after long-term abdominal drain insertion was 29 days
      (8-219). The complication rate was low and none life threatening. CONCLUSION:
      Palliative and end-of-life care needs in end-stage liver disease remain under
      addressed. Our data suggest that long-term abdominal drains may be a safe and
      effective palliative intervention in end-stage liver disease. Prospective
      randomised controlled trials comparing large-volume paracentesis versus long-term
      abdominal drains in refractory ascites secondary to end-stage liver disease are
      warranted.

PMID- 27707957
TI  - Preliminary study on Emodin alleviating alpha-naphthylisothiocyanate-induced
      intrahepatic cholestasis by regulation of liver farnesoid X receptor pathway.
AB  - The aim of this study is to investigate Emodin on alleviating intrahepatic
      cholestasis by regulation of liver farnesoid X receptor (FXR) pathway. Cell and
      animal models of intrahepatic cholestatis were established. Biochemical tests and
      histomorphology were performed. The messenger RNA (mRNA) and protein expression
      of FXR, small heterodimer partner (SHP), uridine diphosphate
      glucuronosyltransferase 2 family polypeptide B4 (UGT2B4), and bile salt export
      pump (BSEP) was detected. As a result, compared with the model group, the serum
      levels of biochemical test were significantly lower in the Emodin group (P
      <0.01). The histopathological changes were remitted significantly by Emodin
      treatment. In the model group, the mRNA and protein expression of FXR, SHP,
      UGT2B4, and BSEP was significantly lower than in the normal group in cell models
      (P <0.05). With Emodin intervention, the expression of FXR, SHP, UGT2B4, and BSEP
      was notably increased (P <0.05). In conclusion, Emodin plays a protective role in
      intrahepatic cholestasis by promoting FXR signal pathways.

PMID- 27707959
TI  - New Online Platform Will Allow Early Release, Alt-metrics, and Extended Datasets.

PMID- 27707958
TI  - A concise review on advances in development of small molecule anti-inflammatory
      therapeutics emphasising AMPK: An emerging target.
AB  - Inflammatory diseases are complex, multi-factorial outcomes of evolutionarily
      conserved tissue repair processes. For decades, non-steroidal anti-inflammatory
      drugs and cyclooxygenase inhibitors, the primary drugs of choice for the
      management of inflammatory diseases, addressed individual targets in the
      arachidonic acid pathway. Unsatisfactory safety and efficacy profiles of the
      above have necessitated the development of multi-target agents to treat complex
      inflammatory diseases. Current anti-inflammatory therapies still fall short of
      clinical needs and the clinical trial results of multi-target therapeutics are
      anticipated. Additionally, new drug targets are emerging with improved
      understanding of molecular mechanisms controlling the pathophysiology of
      inflammation. This review presents an outline of small molecules and drug targets
      in anti-inflammatory therapeutics with a summary of a newly identified target AMP
      activated protein kinase, which constitutes a novel therapeutic pathway in
      inflammatory pathology.

PMID- 27707961
TI  - Synapse-Specific Reinnervation in the Injured Brain.

PMID- 27707962
TI  - Reality of Inhibitory GABA in Neonatal Brain: Time to Rewrite the Textbooks?

PMID- 27707960
TI  - Drug-Induced Alterations of Endocannabinoid-Mediated Plasticity in Brain Reward
      Regions.
AB  - The endocannabinoid (eCB) system has emerged as one of the most important
      mediators of physiological and pathological reward-related synaptic plasticity.
      eCBs are retrograde messengers that provide feedback inhibition, resulting in the
      suppression of neurotransmitter release at both excitatory and inhibitory
      synapses, and they serve a critical role in the spatiotemporal regulation of both
      short- and long-term synaptic plasticity that supports adaptive learning of
      reward-motivated behaviors. However, mechanisms of eCB-mediated synaptic
      plasticity in reward areas of the brain are impaired following exposure to drugs
      of abuse. Because of this, it is theorized that maladaptive eCB signaling may
      contribute to the development and maintenance of addiction-related behavior. Here
      we review various forms of eCB-mediated synaptic plasticity present in regions of
      the brain involved in reward and reinforcement and explore the potential
      physiological relevance of maladaptive eCB signaling to addiction vulnerability.

PMID- 27707963
TI  - Disruption of Protein Processing in the Endoplasmic Reticulum of DYT1 Knock-in
      Mice Implicates Novel Pathways in Dystonia Pathogenesis.
AB  - : Dystonia type 1 (DYT1) is a dominantly inherited neurological disease caused by
      mutations in TOR1A, the gene encoding the endoplasmic reticulum (ER)-resident
      protein torsinA. Previous work mostly completed in cell-based systems suggests
      that mutant torsinA alters protein processing in the secretory pathway. We
      hypothesized that inducing ER stress in the mammalian brain in vivo would trigger
      or exacerbate mutant torsinA-induced dysfunction. To test this hypothesis, we
      crossed DYT1 knock-in with p58(IPK)-null mice. The ER co-chaperone p58(IPK)
      interacts with BiP and assists in protein maturation by helping to fold ER cargo.
      Its deletion increases the cellular sensitivity to ER stress. We found a lower
      generation of DYT1 knock-in/p58 knock-out mice than expected from this cross,
      suggesting a developmental interaction that influences viability. However,
      surviving animals did not exhibit abnormal motor function. Analysis of brain
      tissue uncovered dysregulation of eiF2alpha and Akt/mTOR translational control
      pathways in the DYT1 brain, a finding confirmed in a second rodent model and in
      human brain. Finally, an unbiased proteomic analysis identified relevant changes
      in the neuronal protein landscape suggesting abnormal ER protein metabolism and
      calcium dysregulation. Functional studies confirmed the interaction between the
      DYT1 genotype and neuronal calcium dynamics. Overall, these findings advance our
      knowledge on dystonia, linking translational control pathways and calcium
      physiology to dystonia pathogenesis and identifying potential new pharmacological
      targets. SIGNIFICANCE STATEMENT: Dystonia type 1 (DYT1) is one of the different
      forms of inherited dystonia, a neurological disorder characterized by
      involuntary, disabling movements. DYT1 is caused by mutations in the gene that
      encodes the endoplasmic reticulum (ER)-resident protein torsinA. How mutant
      torsinA causes neuronal dysfunction remains unknown. Here, we show the behavioral
      and molecular consequences of stressing the ER in DYT1 mice by increasing the
      amount of misfolded proteins. This resulted in the generation of a reduced number
      of animals, evidence of abnormal ER protein processing and dysregulation of
      translational control pathways. The work described here proposes a shared
      mechanism for different forms of dystonia, links for the first time known
      biological pathways to dystonia pathogenesis, and uncovers potential
      pharmacological targets for its treatment.

PMID- 27707964
TI  - Functional Subdomains within Scene-Selective Cortex: Parahippocampal Place Area,
      Retrosplenial Complex, and Occipital Place Area.
AB  - : Functional MRI studies suggest that at least three brain regions in human
      visual cortex-the parahippocampal place area (PPA), retrosplenial complex (RSC),
      and occipital place area (OPA; often called the transverse occipital sulcus)
      represent large-scale information in natural scenes. Tuning of voxels within each
      region is often assumed to be functionally homogeneous. To test this assumption,
      we recorded blood oxygenation level-dependent responses during passive viewing of
      complex natural movies. We then used a voxelwise modeling framework to estimate
      voxelwise category tuning profiles within each scene-selective region. In all
      three regions, cluster analysis of the voxelwise tuning profiles reveals two
      functional subdomains that differ primarily in their responses to animals, man
      made objects, social communication, and movement. Thus, the conventional
      functional definitions of the PPA, RSC, and OPA appear to be too coarse. One
      attractive hypothesis is that this consistent functional subdivision of scene
      selective regions is a reflection of an underlying anatomical organization into
      two separate processing streams, one selectively biased toward static stimuli and
      one biased toward dynamic stimuli. SIGNIFICANCE STATEMENT: Visual scene
      perception is a critical ability to survive in the real world. It is therefore
      reasonable to assume that the human brain contains neural circuitry selective for
      visual scenes. Here we show that responses in three scene-selective areas
      identified in previous studies-carry information about many object and action
      categories encountered in daily life. We identify two subregions in each area:
      one that is selective for categories of man-made objects, and another that is
      selective for vehicles and locomotion-related action categories that appear in
      dynamic scenes. This consistent functional subdivision may reflect an anatomical
      organization into two processing streams, one biased toward static stimuli and
      one biased toward dynamic stimuli.

PMID- 27707966
TI  - Neuregulin-Dependent Regulation of Fast-Spiking Interneuron Excitability Controls
      the Timing of the Critical Period.
AB  - : Maturation of excitatory drive onto fast-spiking interneurons (FS INs) in the
      visual cortex has been implicated in the control of the timing of the critical
      period for ocular dominance plasticity. However, the mechanisms that regulate the
      strength of these synapses over cortical development are not understood. Here we
      use a mouse model to show that neuregulin (NRG) and the receptor tyrosine kinase
      erbB4 regulate the timing of the critical period. NRG1 enhanced the strength of
      excitatory synapses onto FS INs, which inhibited ocular dominance plasticity
      during the critical period but rescued plasticity in transgenics with
      hypoexcitable FS INs. Blocking the effects of endogenous neuregulin via
      inhibition of erbBs rescued ocular dominance plasticity in postcritical period
      adults, allowing recovery from amblyopia induced by chronic monocular
      deprivation. Thus, the strength of excitation onto FS INs is a key determinant of
      critical period plasticity and is maintained at high levels by NRG-erbB4
      signaling to constrain plasticity in adulthood. SIGNIFICANCE STATEMENT: Despite
      decades of experimentation, the mechanisms by which critical periods of enhanced
      synaptic plasticity are initiated and terminated are not completely understood.
      Here we show that neuregulin (NRG) and the receptor tyrosine kinase erbB4
      determine critical period timing by controlling the strength of excitatory
      synapses onto FS INs. NRG1 enhanced excitatory drive onto fast spiking
      interneurons, which inhibited ocular dominance plasticity in juveniles but
      rescued plasticity in transgenics with hypoexcitable FS INs. Blocking the effects
      of endogenous neuregulin via inhibition of erbBs rescued ocular dominance
      plasticity in adults, allowing recovery from amblyopia induced by chronic
      monocular deprivation. Thus, in contrast to prevailing views of the termination
      of the critical period, active maintenance of strong excitation onto FS INs
      constrains plasticity in adults.

PMID- 27707967
TI  - Neuronal Dystroglycan Is Necessary for Formation and Maintenance of Functional
      CCK-Positive Basket Cell Terminals on Pyramidal Cells.
AB  - : Distinct types of GABAergic interneurons target different subcellular domains
      of pyramidal cells, thereby shaping pyramidal cell activity patterns. Whether the
      presynaptic heterogeneity of GABAergic innervation is mirrored by specific
      postsynaptic factors is largely unexplored. Here we show that dystroglycan, a
      protein responsible for the majority of congenital muscular dystrophies when
      dysfunctional, has a function at postsynaptic sites restricted to a subset of
      GABAergic interneurons. Conditional deletion of Dag1, encoding dystroglycan, in
      pyramidal cells caused loss of CCK-positive basket cell terminals in hippocampus
      and neocortex. PV-positive basket cell terminals were unaffected in mutant mice,
      demonstrating interneuron subtype-specific function of dystroglycan. Loss of
      dystroglycan in pyramidal cells had little influence on clustering of other
      GABAergic postsynaptic proteins and of glutamatergic synaptic proteins. CCK
      positive terminals were not established at P21 in the absence of dystroglycan and
      were markedly reduced when dystroglycan was ablated in adult mice, suggesting a
      role for dystroglycan in both formation and maintenance of CCK-positive
      terminals. The necessity of neuronal dystroglycan for functional innervation by
      CCK-positive basket cell axon terminals was confirmed by reduced frequency of
      inhibitory events in pyramidal cells of dystroglycan-deficient mice and further
      corroborated by the inefficiency of carbachol to increase IPSC frequency in these
      cells. Finally, neurexin binding seems dispensable for dystroglycan function
      because knock-in mice expressing binding-deficient T190M dystroglycan displayed
      normal CCK-positive terminals. Together, we describe a novel function of
      dystroglycan in interneuron subtype-specific trans-synaptic signaling, revealing
      correlation of presynaptic and postsynaptic molecular diversity. SIGNIFICANCE
      STATEMENT: Dystroglycan, an extracellular and transmembrane protein of the
      dystrophin-glycoprotein complex, is at the center of molecular studies of
      muscular dystrophies. Although its synaptic distribution in cortical brain
      regions is long established, function of dystroglycan in the synapse remained
      obscure. Using mice that selectively lack neuronal dystroglycan, we provide
      evidence that a subset of GABAergic interneurons requires dystroglycan for
      formation and maintenance of axonal terminals on pyramidal cells. As such,
      dystroglycan is the first postsynaptic GABAergic protein for which an interneuron
      terminal-specific function could be shown. Our findings also offer a new
      perspective on the mechanisms that lead to intellectual disability in muscular
      dystrophies without associated brain malformations.

PMID- 27707965
TI  - Basal Ganglia Output Controls Active Avoidance Behavior.
AB  - : Engrained avoidance behavior is highly adaptive when it keeps away harmful
      events and can be highly maladaptive when individuals elude harmless situations
      in anxiety disorders, but the neural circuits that mediate avoidance are poorly
      understood. Using DREADDs and optogenetics in mice, we show that the output of
      the basal ganglia through the substantia nigra pars reticulata (SNr) controls
      active avoidance. SNr excitation blocks avoidance to a conditioned sensory
      stimulus while preserving the ability to escape the harmful event. Conversely,
      SNr inhibition facilitates avoidance to the conditioned stimulus and suffices to
      drive avoidance without any conditioned sensory stimulus. The results highlight a
      midbrain circuit that gates avoidance responses, which can be targeted to
      ameliorate maladaptive avoidance in psychiatric disorders. SIGNIFICANCE
      STATEMENT: In many circumstances, subjects respond to fearful situations with
      avoidance. This is a useful coping strategy in situations in which there is
      impending danger. However, avoidance responses can also be maladaptive, as in
      anxiety disorders such as phobias (e.g., avoiding air transportation) and social
      anxiety (e.g., avoiding social situations). Despite the obvious clinical
      relevance, little is known about the neural circuits that mediate active
      avoidance. Using chemogenetics and optogenetics, we show that the output of the
      basal ganglia fully controls active avoidance behavior.

PMID- 27707969
TI  - Predictions Shape Confidence in Right Inferior Frontal Gyrus.
AB  - : It is clear that prior expectations shape perceptual decision-making, yet their
      contribution to the construction of subjective decision confidence remains
      largely unexplored. We recorded fMRI data while participants made perceptual
      decisions and confidence judgments, manipulating perceptual prior expectations
      while controlling for potential confounds of attention. Results show that
      subjective confidence increases as expectations increasingly support the
      decision, and that this relationship is associated with BOLD activity in right
      inferior frontal gyrus (rIFG). Specifically, rIFG is sensitive to the discrepancy
      between expectation and decision (mismatch), and higher mismatch responses are
      associated with lower decision confidence. Connectivity analyses revealed
      expectancy information to be represented in bilateral orbitofrontal cortex and
      sensory signals to be represented in intracalcarine sulcus. Together, our results
      indicate that predictive information is integrated into subjective confidence in
      rIFG, and reveal an occipital-frontal network that constructs confidence from top
      down and bottom-up signals. This interpretation was further supported by
      exploratory findings that the white matter density of right orbitofrontal cortex
      negatively predicted its respective contribution to the construction of
      confidence. Our findings advance our understanding of the neural basis of
      subjective perceptual processes by revealing an occipitofrontal functional
      network that integrates prior beliefs into the construction of confidence.
      SIGNIFICANCE STATEMENT: Perceptual decision-making is typically conceived as an
      integration of bottom-up and top-down influences. However, perceptual decisions
      are accompanied by a sense of confidence. Confidence is an important facet of
      perceptual consciousness yet remains poorly understood. Here we implicate right
      inferior frontal gyrus in constructing confidence from the discrepancy between
      perceptual judgment and its prior probability. Furthermore, we place right
      inferior frontal gyrus within an occipitofrontal network, consisting of
      orbitofrontal cortex and intracalcarine sulcus, which represents and communicates
      relevant top-down and bottom-up signals. Together, our data reveal a role of
      frontal regions in the top-down processes enabling perceptual decisions to become
      available for conscious report.

PMID- 27707968
TI  - Role of Prefrontal Cortex in Learning and Generalizing Hierarchical Rules in 8
      Month-Old Infants.
AB  - : Recent research indicates that adults and infants spontaneously create and
      generalize hierarchical rule sets during incidental learning. Computational
      models and empirical data suggest that, in adults, this process is supported by
      circuits linking prefrontal cortex (PFC) with striatum and their modulation by
      dopamine, but the neural circuits supporting this form of learning in infants are
      largely unknown. We used near-infrared spectroscopy to record PFC activity in 8
      month-old human infants during a simple audiovisual hierarchical-rule-learning
      task. Behavioral results confirmed that infants adopted hierarchical rule sets to
      learn and generalize spoken object-label mappings across different speaker
      contexts. Infants had increased activity over right dorsal lateral PFC when rule
      sets switched from one trial to the next, a neural marker related to updating
      rule sets into working memory in the adult literature. Infants' eye blink rate, a
      possible physiological correlate of striatal dopamine activity, also increased
      when rule sets switched from one trial to the next. Moreover, the increase in
      right dorsolateral PFC activity in conjunction with eye blink rate also predicted
      infants' generalization ability, providing exploratory evidence for
      frontostriatal involvement during learning. These findings provide evidence that
      PFC is involved in rudimentary hierarchical rule learning in 8-month-old infants,
      an ability that was previously thought to emerge later in life in concert with
      PFC maturation. SIGNIFICANCE STATEMENT: Hierarchical rule learning is a powerful
      learning mechanism that allows rules to be selected in a context-appropriate
      fashion and transferred or reused in novel contexts. Data from computational
      models and adults suggests that this learning mechanism is supported by dopamine
      innervated interactions between prefrontal cortex (PFC) and striatum. Here, we
      provide evidence that PFC also supports hierarchical rule learning during
      infancy, challenging the current dogma that PFC is an underdeveloped brain system
      until adolescence. These results add new insights into the neurobiological
      mechanisms available to support learning and generalization in very early
      postnatal life, providing evidence that PFC and the frontostriatal circuitry are
      involved in organizing learning and behavior earlier in life than previously
      known.

PMID- 27707970
TI  - A RET-ER81-NRG1 Signaling Pathway Drives the Development of Pacinian Corpuscles.
AB  - : Axon-Schwann cell interactions are crucial for the development, function, and
      repair of the peripheral nervous system, but mechanisms underlying communication
      between axons and nonmyelinating Schwann cells are unclear. Here, we show that
      ER81 is functionally required in a subset of mouse RET+ mechanosensory neurons
      for formation of Pacinian corpuscles, which are composed of a single myelinated
      axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for
      the maintenance of Er81 expression. Interestingly, Er81 mutants have normal
      myelination but exhibit deficient interactions between axons and corpuscle
      forming nonmyelinating Schwann cells. Finally, ablating Neuregulin-1 (Nrg1) in
      mechanosensory neurons results in no Pacinian corpuscles, and an Nrg1 isoform not
      required for communication with myelinating Schwann cells is specifically
      decreased in Er81-null somatosensory neurons. Collectively, our results suggest
      that a RET-ER81-NRG1 signaling pathway promotes axon communication with
      nonmyelinating Schwann cells, and that neurons use distinct mechanisms to
      interact with different types of Schwann cells. SIGNIFICANCE STATEMENT:
      Communication between neurons and Schwann cells is critical for development,
      normal function, and regeneration of the peripheral nervous system. Despite many
      studies about axonal communication with myelinating Schwann cells, mostly via a
      specific isoform of Neuregulin1, the molecular nature of axonal communication
      with nonmyelinating Schwann cells is poorly understood. Here, we described a RET
      ER81-Neuregulin1 signaling pathway in neurons innervating Pacinian corpuscle
      somatosensory end organs, which is essential for communication between the
      innervating axon and the end organ nonmyelinating Schwann cells. We also showed
      that this signaling pathway uses isoforms of Neuregulin1 that are not involved in
      myelination, providing evidence that neurons use different isoforms of
      Neuregulin1 to interact with different types of Schwann cells.

PMID- 27707971
TI  - Thyroid Hormone Acts Locally to Increase Neurogenesis, Neuronal Differentiation,
      and Dendritic Arbor Elaboration in the Tadpole Visual System.
AB  - : Thyroid hormone (TH) regulates many cellular events underlying perinatal brain
      development in vertebrates. Whether and how TH regulates brain development when
      neural circuits are first forming is less clear. Furthermore, although the
      molecular mechanisms that impose spatiotemporal constraints on TH action in the
      brain have been described, the effects of local TH signaling are poorly
      understood. We determined the effects of manipulating TH signaling on development
      of the optic tectum in stage 46-49 Xenopus laevis tadpoles. Global TH treatment
      caused large-scale morphological effects in tadpoles, including changes in brain
      morphology and increased tectal cell proliferation. Either increasing or
      decreasing endogenous TH signaling in tectum, by combining targeted DIO3
      knockdown and methimazole, led to corresponding changes in tectal cell
      proliferation. Local increases in TH, accomplished by injecting suspensions of
      tri-iodothyronine (T3) in coconut oil into the midbrain ventricle or into the
      eye, selectively increased tectal or retinal cell proliferation, respectively. In
      vivo time-lapse imaging demonstrated that local TH first increased tectal
      progenitor cell proliferation, expanding the progenitor pool, and subsequently
      increased neuronal differentiation. Local T3 also dramatically increased
      dendritic arbor growth in neurons that had already reached a growth plateau. The
      time-lapse data indicate that the same cells are differentially sensitive to T3
      at different time points. Finally, TH increased expression of genes pertaining to
      proliferation and neuronal differentiation. These experiments indicate that
      endogenous TH locally regulates neurogenesis at developmental stages relevant to
      circuit assembly by affecting cell proliferation and differentiation and by
      acting on neurons to increase dendritic arbor elaboration. SIGNIFICANCE
      STATEMENT: Thyroid hormone (TH) is a critical regulator of perinatal brain
      development in vertebrates. Abnormal TH signaling in early pregnancy is
      associated with significant cognitive deficits in humans; however, it is
      difficult to probe the function of TH in early brain development in mammals
      because of the inaccessibility of the fetal brain in the uterine environment and
      the challenge of disambiguating maternal versus fetal contributions of TH. The
      external development of tadpoles allows manipulation and direct observation of
      the molecular and cellular mechanisms underlying TH's effects on brain
      development in ways not possible in mammals. We find that endogenous TH locally
      regulates neurogenesis at developmental stages relevant to circuit assembly by
      affecting neural progenitor cell proliferation and differentiation and by acting
      on neurons to enhance dendritic arbor elaboration.

PMID- 27707972
TI  - Methamphetamine Regulation of Firing Activity of Dopamine Neurons.
AB  - : Methamphetamine (METH) is a substrate for the dopamine transporter that
      increases extracellular dopamine levels by competing with dopamine uptake and
      increasing reverse transport of dopamine via the transporter. METH has also been
      shown to alter the excitability of dopamine neurons. The mechanism of METH
      regulation of the intrinsic firing behaviors of dopamine neurons is less
      understood. Here we identified an unexpected and unique property of METH on the
      regulation of firing activity of mouse dopamine neurons. METH produced a
      transient augmentation of spontaneous spike activity of midbrain dopamine neurons
      that was followed by a progressive reduction of spontaneous spike activity.
      Inspection of action potential morphology revealed that METH increased the half
      width and produced larger coefficients of variation of the interspike interval,
      suggesting that METH exposure affected the activity of voltage-dependent
      potassium channels in these neurons. Since METH has been shown to affect Ca2+
      homeostasis, the unexpected findings that METH broadened the action potential and
      decreased the amplitude of afterhyperpolarization led us to ask whether METH
      alters the activity of Ca2+-activated potassium (BK) channels. First, we
      identified BK channels in dopamine neurons by their voltage dependence and their
      response to a BK channel blocker or opener. While METH suppressed the amplitude
      of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated
      the effects of METH on action potential broadening, afterhyperpolarization
      repression, and spontaneous spike activity reduction. Live-cell total internal
      reflection fluorescence microscopy, electrophysiology, and biochemical analysis
      suggest METH exposure decreased the activity of BK channels by decreasing BK
      alpha subunit levels at the plasma membrane. SIGNIFICANCE STATEMENT:
      Methamphetamine (METH) competes with dopamine uptake, increases dopamine efflux
      via the dopamine transporter, and affects the excitability of dopamine neurons.
      Here, we identified an unexpected property of METH on dopamine neuron firing
      activity. METH transiently increased the spontaneous spike activity of dopamine
      neurons followed by a progressive reduction of the spontaneous spike activity.
      METH broadened the action potentials, increased coefficients of variation of the
      interspike interval, and decreased the amplitude of afterhyperpolarization, which
      are consistent with changes in the activity of Ca2+-activated potassium (BK)
      channels. We found that METH decreased the activity of BK channels by stimulating
      BK-alpha subunit trafficking. Thus, METH modulation of dopamine neurotransmission
      and resulting behavioral responses is, in part, due to METH regulation of BK
      channel activity.

PMID- 27707973
TI  - T394A Mutation at the MU Opioid Receptor Blocks Opioid Tolerance and Increases
      Vulnerability to Heroin Self-Administration in Mice.
AB  - : The etiology and pathophysiology underlying opioid tolerance and dependence are
      still unknown. Because mu opioid receptor (MOR) plays an essential role in opioid
      action, many vulnerability-related studies have focused on single nucleotide
      polymorphisms of MOR, particularly on A118G. In this study, we found that a
      single-point mutation at the MOR T394 phosphorylation site could be another
      important susceptive factor in the development of opioid tolerance and dependence
      in mice. T394A mutation, in which a threonine at 394 was replaced by an alanine,
      did not alter agonist binding to MOR and opioid analgesia, but resulted in loss
      of etorphine-induced MOR internalization in spinal dorsal horn neurons and opioid
      analgesic tolerance induced by either morphine or etorphine. In addition, this
      mutation also caused an increase in intravenous heroin self-administration and in
      nucleus accumbens dopamine response to heroin. These findings suggest that T394
      phosphorylation following MOR activation causes MOR internalization and
      desensitization, which subsequently contributes to the development of tolerance
      in both opioid analgesia and opioid reward. Accordingly, T394A mutation blocks
      opioid tolerance and leads to an increase in brain dopamine response to opioids
      and in opioid-taking behavior. Thus, the T394 may serve as a new drug target for
      modulating opioid tolerance and the development of opioid abuse and addiction.
      SIGNIFICANCE STATEMENT: The mechanisms underlying opioid tolerance and
      susceptibility to opioid addiction remain unclear. The present studies
      demonstrate that a single-point mutation at the T394 phosphorylation site in the
      C-terminal of mu opioid receptor (MOR) results in loss of opioid tolerance and
      enhanced vulnerability to heroin self-administration. These findings suggest that
      modulation of the MOR-T394 phosphorylation or dephosphorylation status may have
      therapeutic potential in management of pain, opioid tolerance, and opioid abuse
      and addiction. Accordingly, MOR-T394 mutation or polymorphisms could be a risk
      factor in developing opioid abuse and addiction and therefore be used as a new
      biomarker in prediction and prevention of opioid abuse and addiction.

PMID- 27707974
TI  - Glutamate Clearance Is Locally Modulated by Presynaptic Neuronal Activity in the
      Cerebral Cortex.
AB  - : Excitatory amino acid transporters (EAATs) are abundantly expressed by
      astrocytes, rapidly remove glutamate from the extracellular environment, and
      restrict the temporal and spatial extent of glutamate signaling. Studies probing
      EAAT function suggest that their capacity to remove glutamate is large and does
      not saturate, even with substantial glutamate challenges. In contrast, we report
      that neuronal activity rapidly and reversibly modulates EAAT-dependent glutamate
      transport. To date, no physiological manipulation has shown changes in functional
      glutamate uptake in a nonpathological state. Using iGluSnFr-based glutamate
      imaging and electrophysiology in the adult mouse cortex, we show that glutamate
      uptake is slowed up to threefold following bursts of neuronal activity. The
      slowing of glutamate uptake depends on the frequency and duration of presynaptic
      neuronal activity but is independent of the amount of glutamate released. The
      modulation of glutamate uptake is brief, returning to normal within 50 ms after
      stimulation ceases. Interestingly, the slowing of glutamate uptake is specific to
      activated synapses, even within the domain of an individual astrocyte. Activity
      induced slowing of glutamate uptake, and the increased persistence of glutamate
      in the extracellular space, is reflected by increased decay times of neuronal
      NR2A-mediated NMDA currents. These results show that astrocytic clearance of
      extracellular glutamate is slowed in a temporally and spatially specific manner
      following bursts of neuronal activity >=30 Hz and that these changes affect the
      neuronal response to released glutamate. This suggests a previously unreported
      form of neuron-astrocyte interaction. SIGNIFICANCE STATEMENT: We report the first
      fast, physiological modulation of astrocyte glutamate clearance kinetics. We show
      that presynaptic activity in the cerebral cortex increases the persistence of
      glutamate in the extracellular space by slowing its clearance by astrocytes.
      Because of abundant EAAT expression, glutamate clearance from the extracellular
      space has been thought to have invariant kinetics. While multiple studies report
      experimental manipulations resulting in altered EAAT expression, our findings
      show that astrocytic glutamate uptake is dynamic on a fast time-scale. This shows
      rapid plasticity of glutamate clearance, which locally modulates synaptic
      signaling in the cortex. As astrocytic glutamate uptake is a fundamental and
      essential mechanism for neurotransmission, this work has implications for
      neurotransmission, extrasynaptic receptor activation, and synaptic plasticity.

PMID- 27707977
TI  - Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors.
AB  - : Contrary to cats and primates, cortical contribution to hindlimb locomotor
      movements is not critical in rats. However, the importance of the motor cortex to
      regain locomotion after neurological disorders in rats suggests that cortical
      engagement in hindlimb motor control may depend on the behavioral context. To
      investigate this possibility, we recorded whole-body kinematics, muscle
      synergies, and hindlimb motor cortex modulation in freely moving rats performing
      a range of natural locomotor procedures. We found that the activation of hindlimb
      motor cortex preceded gait initiation. During overground locomotion, the motor
      cortex exhibited consistent neuronal population responses that were synchronized
      with the spatiotemporal activation of hindlimb motoneurons. Behaviors requiring
      enhanced muscle activity or skilled paw placement correlated with substantial
      adjustment in neuronal population responses. In contrast, all rats exhibited a
      reduction of cortical activity during more automated behavior, such as stepping
      on a treadmill. Despite the facultative role of the motor cortex in the
      production of locomotion in rats, these results show that the encoding of
      hindlimb features in motor cortex dynamics is comparable in rats and cats.
      However, the extent of motor cortex modulations appears linked to the degree of
      volitional engagement and complexity of the task, reemphasizing the importance of
      goal-directed behaviors for motor control studies, rehabilitation, and
      neuroprosthetics. SIGNIFICANCE STATEMENT: We mapped the neuronal population
      responses in the hindlimb motor cortex to hindlimb kinematics and hindlimb muscle
      synergies across a spectrum of natural locomotion behaviors. Robust task-specific
      neuronal population responses revealed that the rat motor cortex displays similar
      modulation as other mammals during locomotion. However, the reduced motor cortex
      activity during more automated behaviors suggests a relationship between the
      degree of engagement and task complexity. This relationship emphasizes the
      importance of the behavioral procedure to engage the motor cortex during motor
      control studies, gait rehabilitation, and locomotor neuroprosthetic developments
      in rats.

PMID- 27707976
TI  - Proliferation and Survival of Embryonic Sympathetic Neuroblasts by MYCN and
      Activated ALK Signaling.
AB  - : Neuroblastoma (NB) is a childhood tumor that arises from the sympathoadrenal
      lineage. MYCN amplification is the most reliable marker for poor prognosis and
      MYCN overexpression in embryonic mouse sympathetic ganglia results in NB-like
      tumors. MYCN cooperates with mutational activation of anaplastic lymphoma kinase
      (ALK), which promotes progression to NB, but the role of MYCN and ALK in
      tumorigenesis is still poorly understood. Here, we use chick sympathetic
      neuroblasts to examine the normal function of MYCN and MYC in the control of
      neuroblast proliferation, as well as effects of overexpression of MYCN, MYC, and
      activated ALK, alone and in combination. We demonstrate that MYC is more strongly
      expressed than MYCN during neurogenesis and is important for in vitro neuroblast
      proliferation. MYC and MYCN overexpression elicits increased proliferation but
      does not sustain neuroblast survival. Unexpectedly, long-term expression of
      activated ALKF1174L leads to cell-cycle arrest and promotes differentiation and
      survival of postmitotic neurons. ALKF1174L induces NEFM, RET, and VACHT and
      results in decreased expression of proapototic (BMF, BIM), adrenergic (TH), and
      cell-cycle genes (e.g., CDC25A, CDK1). In contrast, neuroblast proliferation is
      maintained when MYCN and ALKF1174L are coexpressed. Proliferating MYCN/ALKF1174L
      neuroblasts display a differentiated phenotype but differ from ALK-expressing
      neurons by the upregulation of SKP2, CCNA2, E2F8, and DKC1 Inhibition of the
      ubiquitin ligase SKP2 (S-phase kinase-associated protein 2), which targets the
      CDK inhibitor p27 for degradation, reduces neuroblast proliferation, implicating
      SKP2 in the maintained proliferation of MYCN/ALKF1174L neuroblasts. Together, our
      results characterize MYCN/ALK cooperation leading to neuroblast proliferation and
      survival that may represent initial steps toward NB development. SIGNIFICANCE
      STATEMENT: MYCN overexpression combined with activated anaplastic lymphoma kinase
      (ALK) is sufficient to induce neuroblastoma (NB) in mouse sympathoadrenal cells.
      To address cellular and molecular effects elicited by MYCN/ALK cooperation, we
      used cultures of chick sympathetic neuroblasts. We demonstrate that MYCN
      increases proliferation but not survival, whereas long-term expression of
      ALKF1174L elicits cell-cycle exit, differentiation, and survival of postmitotic
      neurons. Combined MYCN/ALKF1174L expression allows long-term proliferation and
      survival of neuroblasts with differentiated characteristics. In the presence of
      ALKF1174L signaling, MYCN induces the expression of the ubiquitin ligase SKP2 (S
      phase kinase-associated protein 2), which targets p27 for degradation and is also
      upregulated in high-risk NB. SKP2 inhibition supports a function for SKP2 in the
      maintained neuroblast proliferation downstream of MYCN/ALK, which may represent
      an early step toward tumorigenesis.

PMID- 27707975
TI  - Effect of Ovarian Hormone Therapy on Cognition in the Aged Female Rhesus Macaque.
AB  - : Studies of the effect of hormone therapy on cognitive function in menopausal
      women have been equivocal, in part due to differences in the type and timing of
      hormone treatment. Here we cognitively tested aged female rhesus macaques on (1)
      the delayed response task of spatial working memory, (2) a visuospatial attention
      task that measured spatially and temporally cued reaction times, and (3) a simple
      reaction time task as a control for motor speed. After task acquisition, animals
      were ovariectomized (OVX). Their performance was compared with intact controls
      for 2 months, at which time no group differences were found. The OVX animals were
      then assigned to treatment with either a subcutaneous sham implant (OVX), 17-beta
      estradiol (E) implant (OVX+E) or E implant plus cyclic oral progesterone
      (OVX+EP). All groups were then tested repeatedly over 12 months. The OVX+E
      animals performed significantly better on the delayed response task than all of
      the other groups for much of the 12 month testing period. The OVX+EP animals also
      showed improved performance in the delayed response task, but only at 30 s delays
      and with performance levels below that of OVX+E animals. The OVX+E animals also
      performed significantly better in the visuospatial attention task, particularly
      in the most challenging invalid cue condition; this difference also was
      maintained across the 12 month testing period. Simple reaction time was not
      affected by hormonal manipulation. These data demonstrate that chronic,
      continuous administration of E can exert multiple beneficial cognitive effects in
      aged, OVX rhesus macaque females. SIGNIFICANCE STATEMENT: Hormone therapy after
      menopause is controversial. We tested the effects of hormone replacement in aged
      rhesus macaques, soon after surgically-induced menopause [ovariectomy (OVX)], on
      tests of memory and attention. Untreated ovarian-intact and OVX animals were
      compared with OVX animals receiving estradiol (E) alone or E with progesterone
      (P). E was administered in a continuous fashion via subcutaneous implant, whereas
      P was administered orally in a cyclic fashion. On both tests, E-treated animals
      performed better than the other 3 experimental groups across 1 year of treatment.
      Thus, in this monkey model, chronic E administered soon after the loss of ovarian
      hormones had long-term benefits for cognitive function.

PMID- 27707979
TI  - APOE-Sensitive Cholinergic Sprouting Compensates for Hippocampal Dysfunctions Due
      to Reduced Entorhinal Input.
AB  - : Brain mechanisms compensating for cerebral lesions may mitigate the progression
      of chronic neurodegenerative disorders such as Alzheimer's disease (AD). Mild
      cognitive impairment (MCI), which often precedes AD, is characterized by neuronal
      loss in the entorhinal cortex (EC). This loss leads to a hippocampal
      disconnection syndrome that drives clinical progression. The concomitant
      sprouting of cholinergic terminals in the hippocampus has been proposed to
      compensate for reduced EC glutamatergic input. However, in absence of direct
      experimental evidence, the compensatory nature of the cholinergic sprouting and
      its putative mechanisms remain elusive. Transgenic mice expressing the human
      APOE4 allele, the main genetic risk factor for sporadic MCI/AD, display impaired
      cholinergic sprouting after EC lesion. Using these mice as a tool to manipulate
      cholinergic sprouting in a disease-relevant way, we showed that this sprouting
      was necessary and sufficient for the acute compensation of EC lesion-induced
      spatial memory deficit before a slower glutamatergic reinnervation took place. We
      also found that partial EC lesion generates abnormal hyperactivity in EC/dentate
      networks. Dentate hyperactivity was abolished by optogenetic stimulation of
      cholinergic fibers. Therefore, control of dentate hyperactivity by cholinergic
      sprouting may be involved in functional compensation after entorhinal lesion. Our
      results also suggest that dentate hyperactivity in MCI patients may be directly
      related to EC neuronal loss. Impaired sprouting during the MCI stage may
      contribute to the faster cognitive decline reported in APOE4 carriers. Beyond the
      amyloid contribution, the potential role of both cholinergic sprouting and
      dentate hyperactivity in AD symptomatogenesis should be considered in designing
      new therapeutic approaches. SIGNIFICANCE STATEMENT: Currently, curative treatment
      trials for Alzheimer's disease (AD) have failed. The endogenous ability of the
      brain to cope with neuronal loss probably represents one of the most promising
      therapeutic targets, but the underlying mechanisms are still unclear. Here, we
      show that the mammalian brain is able to manage several deleterious consequences
      of the loss of entorhinal neurons on hippocampal activity and cognitive
      performance through a fast cholinergic sprouting followed by a slower
      glutamatergic reinnervation. The cholinergic sprouting is gender dependent and
      highly sensitive to the genetic risk factor APOE4 Our findings highlight the
      specific impact of early loss of entorhinal input on hippocampal hyperactivity
      and cognitive deficits characterizing early stages of AD, especially in APOE4
      carriers.

PMID- 27707980
TI  - Persistent right ventricular dysfunction, functional capacity limitation,
      exercise intolerance, and quality of life impairment following pulmonary
      embolism: Systematic review with meta-analysis.
AB  - Long-term right ventricular (RV) function, functional capacity, exercise
      capacity, and quality of life following pulmonary embolism (PE), and the impact
      of thrombolysis, are unclear. A systematic review of studies that evaluated these
      outcomes with ? 3-month mean follow-up after PE diagnosis was performed. For each
      outcome, random effects meta-analyses were performed. Twenty-six studies (3671
      patients) with 18-month median follow-up were included. The pooled prevalence of
      RV dysfunction was 18.1%. Patients treated with thrombolysis had a lower, but not
      statistically significant, risk of RV dysfunction versus those treated with
      anticoagulation (odds ratio: 0.51, 95% CI: 0.24 to 1.13, p=0.10). Pooled
      prevalence of at least mild functional impairment (NYHA II-IV) was 33.2%, and at
      least moderate functional impairment (NYHA III-IV) was 11.3%. Patients treated
      with thrombolysis had a lower, but not statistically significant, risk of at
      least moderate functional impairment versus those treated with anticoagulation
      (odds ratio: 0.48, 95% CI: 0.15 to 1.49, p=0.20). Pooled 6-minute walk distance
      was 415 m (95% CI: 372 to 458 m), SF-36 Physical Component Score was 44.8 (95%
      CI: 43 to 46), and Pulmonary Embolism Quality of Life (QoL) Questionnaire total
      score was 9.1. Main limitations included heterogeneity among studies for many
      outcomes, variation in the completeness of data reported, and inclusion of data
      from non-randomized, non-controlled, and retrospective studies. Persistent RV
      dysfunction, impaired functional status, diminished exercise capacity, and
      reduced QoL are common in PE survivors. The effect of thrombolysis on RV function
      and functional status remains unclear.

PMID- 27707981
TI  - Pulmonary hypertension associated with Parkes-Weber syndrome (a rare congenital
      arteriovenous malformation).

PMID- 27707978
TI  - Impact of Visual Corticostriatal Loop Disruption on Neural Processing within the
      Parahippocampal Place Area.
AB  - : The caudate nucleus is a part of the visual corticostriatal loop (VCSL),
      receiving input from different visual areas and projecting back to the same
      cortical areas via globus pallidus, substantia nigra, and thalamus. Despite
      perceptual and navigation impairments in patients with VCSL disruption due to
      caudate atrophy (e.g., Huntington's disease, HD), the relevance of the caudate
      nucleus and VCSL on cortical visual processing is not fully understood. In a
      series of fMRI experiments, we found that the caudate showed a stronger
      functional connection to parahippocampal place area (PPA) compared with adjacent
      regions (e.g., fusiform face area, FFA) within the temporal visual cortex.
      Consistent with this functional link, the caudate showed a higher response to
      scenes compared with faces, similar to the PPA. Testing the impact of VCSL
      disruption on neural processes within PPA, HD patients showed reduced scene
      selective activity within PPA compared with healthy matched controls. In
      contrast, the level of selective activity in adjacent cortical and subcortical
      face-selective areas (i.e., FFA and amygdala) remained intact. These results show
      some of the first evidence for the direct impact and potential clinical
      significance of VCSL on the generation of "selective" activity within PPA.
      SIGNIFICANCE STATEMENT: Visual perception is often considered the product of a
      multistage feedforward neural processing between visual cortical areas, ignoring
      the likely impact of corticosubcortical loops on this process. Here, we provide
      evidence for the contribution of visual corticostriatal loop and the caudate
      nucleus on generating selective response within parahippocampal place area (PPA).
      Our results show that disruption of this loop in Huntington's disease patients
      reduces the level of selective activity within PPA, which may lead to related
      perceptual impairments in these patients.

PMID- 27707982
TI  - Assessment of Renal Injury in Patients Undergoing Elective EVAR Using Urinary
      Neutrophil Gelatin-Associated Lipocalin, Interleukin 18, and Retinol-Binding
      Protein.
AB  - Acute kidney injury (AKI) is a recognized complication post-endovascular aneurysm
      repair (EVAR). Neutrophil gelatin-associated lipocalin (NGAL), interleukin 18 (IL
      18), and retinol-binding protein are emerging urinary biomarkers that have shown
      promise in detecting subclinical and clinical renal impairment. In this study, we
      assessed changes in these urinary biomarkers as well as serum creatinine (SCr) in
      patients undergoing EVAR. Urine samples were collected prospectively at 5 time
      points for each recruited patient: pre-EVAR (baseline) and 6, 12, 24, and 48
      hours after the procedure for serial assessment of urinary biomarkers. Serum
      creatinine was quantified preoperatively and at 24 and 48 hours postoperatively.
      Serial changes of urinary biomarkers and SCr were assessed. A significant
      increase in NGAL and IL-18 from baseline was observed ( P < .05), as early as 6
      hours for NGAL. A significant rise in levels of NGAL and IL-18 precedes the
      significant rise in SCr. These findings highlight the potential of emerging
      urinary biomarkers in detecting early AKI following EVAR.

PMID- 27707983
TI  - Field Comparisons of the Gravid Aedes Trap (GAT) and BG-Sentinel Trap for
      Monitoring Aedes albopictus (Diptera: Culicidae) Populations and Notes on Indoor
      GAT Collections in Vietnam.
AB  - We report on the use of the Gravid Aedes Trap (GAT) as a surveillance device for
      Aedes albopictus (Skuse) relative to the BG-Sentinel (BGS) trap in field studies
      conducted in Trenton, NJ, and on Hammond Island, Queensland, Australia. A
      parallel study conducted in Nha Trang, Vietnam, assessed the use of the GAT as an
      indoor surveillance device as well as the use of canola oil as a noninsecticide
      killing agent. In Trenton and Hammond Island, the GAT collected fewer male (0.40
      +/- 0.12 and 0.43 +/- 0.30, respectively) and female (3.05 +/- 0.67 and 2.7 +/-
      2.3, respectively) Ae. albopictus than the BGS trap (males: 3.54 +/- 1.26 and
      3.75 +/- 0.83; females: 4.66 +/- 1.18 and 3.9 +/- 0.23) over their respective
      sampling periods (i.e., 24 h for the BGS and 1 wk for the GAT). Despite
      differences in capture rates, the percentage of traps positive for female Ae.
      albopictus was similar between the BGS and GAT (Trenton: 60.1 +/- 6.3% and 64.4
      +/- 4.1%; Hammond: 87.5 +/- 6.9% and 80.0 +/- 8.2%). In Nha Trang, the GAT was
      equally effective indoors and outdoors with (10 g hay or 3 g fish food) and
      without (water or empty) infusion. Additionally, no significant decrease in
      collections was observed between GATs set with canola oil or long-lasting
      insecticidal net. In summary, both traps were successful in monitoring female Ae.
      albopictus over their respective trapping intervals, but would be best used to
      complement each other to monitor both sexes and all physiological stages of
      female Ae. albopictus. However, the versatility and low-cost of the GAT makes it
      an attractive alternative to the more expensive BGS trap.

PMID- 27707986
TI  - Putative Sensory Structures Associated With the Food Canal of Tabanus atratus
      (Diptera: Tabanidae).
AB  - Putative sensory structures in the food canal, and distal vestibule region
      entering the canal of Tabanus atratus F., are described. Two pairs of sensilla
      were observed in the walls of the vestibule-a distal pair of the basiconic type,
      and a pair of setifiorm sensilla at the base of the vestibule. Vestibular
      sensilla were constant in type, number, and position. Conversely, setiform
      sensilla in right and left walls of the food canal varied in number from one fly
      specimen to another, and lacked evidence of pairing (i.e., sensilla in one wall
      did not necessarily have a counterpart in the other wall). Food canal sensilla
      were of setiform design, with the exception of a single basiconic sensilla in
      each lateral wall of the food canal in every fly. When the food canal was
      partitioned into four equidistant regions, setiform sensilla were aggregated in
      the two distal-most regions, with relatively few sensilla observed in the two
      proximal canal regions. This aggregation was significant, leading to rejection of
      the null hypothesis that setiform sensilla were evenly distribution throughout
      the length of the food canal. Basiconic sensilla were always located in the
      distal-most region of the food canal.

PMID- 27707988
TI  - Successful outcome of macrolide-resistant Mycoplasma genitalium urethritis after
      spectinomycin treatment: a case report.

PMID- 27707989
TI  - Mixed gonococcal infections in a high-risk population, Sydney, Australia 2015:
      implications for antimicrobial resistance surveillance?
AB  - OBJECTIVES: Previous studies have shown that mixed-strain gonococcal infections
      can occur. However, it remains unclear whether such infections impact upon the
      reliability of Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance.
      In this study, we aimed to resolve this question by intensively sampling isolates
      from gonorrhoea-positive specimens in a high-risk population in Sydney,
      Australia. METHODS: A total of 615 N. gonorrhoeae isolates, originating from 63
      clinical samples (31 rectal swabs and 32 throat swabs), were characterized. All
      isolates were subject to N. gonorrhoeae identification, antimicrobial
      susceptibility testing and genotyping by SNP-based MLST. RESULTS: Only 2 of the
      63 (3.2%) samples provided evidence of mixed-strain infections. These comprised
      two rectal swabs that harboured isolates of different SNP-based MLST genotypes;
      however, the AMR susceptibility profiles of the different genotypes from these
      samples were indistinguishable. Within-sample differences in the AMR
      susceptibility profiles were observed for a further seven samples; however, the
      differences were not considered significant; MIC values were typically within a 2
      fold difference or were close to test breakpoints. CONCLUSIONS: Results of this
      study provide further evidence that mixed-strain gonococcal infections do occur,
      although at low prevalence. Our data indicate that at a population level such
      infections are unlikely to impact significantly upon N. gonorrhoeae AMR
      surveillance.

PMID- 27707990
TI  - Efficacy of ceftolozane/tazobactam against urinary tract and intra-abdominal
      infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae: a
      pooled analysis of Phase 3 clinical trials.
AB  - OBJECTIVES: The increase in infections caused by drug-resistant ESBL-producing
      Enterobacteriaceae (ESBL-ENT) is a global concern. The characteristics and
      outcomes of patients infected with ESBL-ENT were examined in a pooled analysis of
      Phase 3 clinical trials of ceftolozane/tazobactam in patients with complicated
      urinary tract infections (ASPECT-cUTI) and complicated intra-abdominal infections
      (ASPECT-cIAI). METHODS: Trials were randomized and double blind. The ASPECT-cUTI
      regimen was 7 days of either intravenous ceftolozane/tazobactam (1.5 g) every 8 h
      or levofloxacin (750 mg) once daily. The ASPECT-cIAI regimen was 4-14 days of
      either intravenous ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) or
      meropenem (1 g) every 8 h. Baseline cultures were obtained in both indications.
      Enterobacteriaceae were selected for ESBL characterization based on predefined
      criteria and were verified genotypically. Outcomes were assessed at the test-of
      cure visit 5-9 days post-therapy in ASPECT-cUTI and 24-32 days post-randomization
      in ASPECT-cIAI among microbiologically evaluable (ME) patients. RESULTS: Of 2076
      patients randomized, 1346 were included in the pooled ME population and 150 of
      1346 (11.1%) had ESBL-ENT at baseline. At US FDA/EUCAST breakpoints of <=2/<=1
      mg/L, 81.8%/72.3% of ESBL-ENT (ESBL-Escherichia coli, 95%/88.1%; ESBL-Klebsiella
      pneumoniae, 56.7%/36.7%) were susceptible to ceftolozane/tazobactam versus
      25.3%/24.1% susceptible to levofloxacin and 98.3%/98.3% susceptible to meropenem
      at CLSI/EUCAST breakpoints. Clinical cure rates for ME patients with ESBL-ENT
      were 97.4% (76/78) for ceftolozane/tazobactam [ESBL-E. coli, 98.0% (49 of 50);
      ESBL-K. pneumoniae, 94.4% (17 of 18)], 82.6% (38 of 46) for levofloxacin and
      88.5% (23 of 26) for meropenem. CONCLUSIONS: Randomized trial data demonstrated
      high clinical cure rates with ceftolozane/tazobactam treatment of cIAI and cUTI
      caused by ESBL-ENT.

PMID- 27707992
TI  - In vitro 'time-to-kill' assay to assess the cidal activity dynamics of current
      reference drugs against Leishmania donovani and Leishmania infantum.
AB  - OBJECTIVES: Despite a continued search for novel antileishmanial drugs, treatment
      options remain restricted to a few standard drugs, e.g. antimonials, miltefosine,
      amphotericin B and paromomycin. Although these drugs have now been used for
      several decades, their mechanism of action still remains partly hypothetical and
      their dynamics of cidal action and time-to-kill are still poorly documented.
      METHODS: An in vitro time-to-kill assay on intracellular amastigotes of the
      laboratory reference strains Leishmania donovani (MHOM/ET/67/L82) and Leishmania
      infantum [MHOM/MA(BE)/67/ITMAP263] evaluated the cidal action dynamics of the
      listed reference drugs at three different concentrations: at IC50, 2 * IC50 and
      the near cytotoxic dose level (CC90: determined on MRC-5 cells). This assay
      focused on identifying the minimal exposure time needed to completely eliminate
      viable intracellular amastigotes, using the standard microscopic Giemsa assay and
      the promastigote back-transformation assay. RESULTS: While 100% reduction was
      microscopically apparent for most drugs, the promastigote back-transformation
      assay clearly demonstrated a concentration- and time-dependent cidal mechanism.
      The time-to-kill at 2 * IC50 was >=240 h for pentavalent antimony (77 MUg
      eq./mL), 96 h for trivalent antimony (44 MUg eq./mL), 168 to >240 h for
      miltefosine (10 MUM), 168 h for paromomycin (100 MUM) and >240 h for amphotericin
      B (2 MUM). No differences were noted between both Leishmania species.
      CONCLUSIONS: Evaluation of the concentration- and time-dependent cidal activity
      using the promastigote back-transformation assay revealed striking differences in
      efficacy of the different antileishmanial reference drugs. This assay should
      allow in-depth pharmacodynamic evaluation of novel drug leads in comparison with
      the existing antileishmanial drug repertoire.

PMID- 27707994
TI  - Testing multidimensional well-being among university community samples in Italy
      and Serbia.
AB  - Today well-being attracts the attention of public health professionals who are
      looking to explore life satisfaction as a whole and its specific domains. In
      order to contribute in moving the measurement of subjective well-being from a
      primarily academic activity to the sphere of intervention, we need to assess
      tools to measure multidimensional well-being (MWB) adopting state-of-the-art
      statistical techniques. Through structural equation modelling our goal was to
      test a MWB model among Italian and Serbian university students and to further
      observe its relationships with measures of life goals' pursuing. This cross
      sectional pilot study was conducted on a consecutive sample of 86 Italian (45%
      female; Mage = 24.20, SD = 2.02) and 83 Serbian (55% female; Mage = 23.52, SD =
      2.48) university students. Participants filled in an anonymous questionnaire
      investigating: self-perceived MWB, standardized control measures of well-being
      (life satisfaction and eudaimonic well-being), and commitment and stress
      regarding personal goal pursuing. Results evidenced how Serbians reported higher
      scores on MWB and on control measures than Italians. Moreover, the most
      frequently reported goals were to complete studies, to obtain job position and to
      be healthy. Exploratory and multi-group confirmatory factor analyses yielded a
      one-factor solution of MWB across Italian and Serbian sub-groups. MWB resulted
      positively associated with standardized control measures in both national groups.
      The results support the strength of our MWB model applied to samples of young
      university students in Italy and Serbia. Based on such findings, future studies
      may adopt this instrument in larger populations of university students in these
      two countries.

PMID- 27707995
TI  - Glycogen: Multiple Roles in the CNS.
AB  - The historically neurocentric view of astrocytes as Styrofoam cushioning that
      rigidly clad neurons within the brain parenchyma has been superseded in the past
      30 years by an increasing appreciation of the myriad roles astrocytes contribute
      to supporting physiological brain function. It is widely recognized that the
      continuous support provided by astrocytes, from prenatal development to maturity,
      is vital for neuronal function. Indeed, the numerous and diverse roles furnished
      by astrocytes contrasts with the vital but restricted transmission of action
      potentials that is the neuron's primary role. An emerging role for astrocytes is
      that of providing energy substrate in the form of glycogen-derived lactate to
      neurons. This role was established during periods of limited glucose availability
      but has been extended to encompass one of the most important physiological brain
      functions, learning and memory. In this context glycogen metabolism is integral
      to the consolidation of learning into long-term retention of memories, a process
      vital to the higher functioning of the human brain.

PMID- 27707991
TI  - Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of
      nevirapine in African children.
AB  - OBJECTIVES: To characterize the effects of CYP2B6 polymorphisms, diurnal
      variation and demographic factors on nevirapine pharmacokinetics in African
      children. METHODS: Non-linear mixed-effects modelling conducted in NONMEM 7.3
      described nevirapine plasma concentration-time data from 414 children aged 0.3-15
      years. RESULTS: Nevirapine pharmacokinetics was best described using a one
      compartment disposition model with elimination through a well-stirred liver model
      accounting for a first-pass effect and transit-compartment absorption. Intrinsic
      clearance was affected by diurnal variation (characterized using a cosine
      function with peak amplitude 29% at 12 noon) and CYP2B6 metabolizer status
      [extensive metabolizer (EM) 516GG|983TT, reference; intermediate metabolizer (IM)
      516GT|983TT or 516GG|983TC, 17% lower; slow metabolizer (SM) 516TT|983TT or
      516GT|983TC, 50% lower; ultra-slow metabolizer (USM) 516GG|983CC, 68% lower]. Age
      was found to affect pre-hepatic bioavailability: 31.7% lower at birth and
      increasing exponentially. Median (90% CI) evening Cmin values in the different
      metabolizer groups were 5.01 (3.01-7.47), 6.55 (3.65-13.32), 11.59 (5.44-22.71)
      and 12.32 (12.32-27.25) mg/L, respectively. Evening Cmin values were <3 mg/L in
      43% of EM weighing <6 kg and 26% of IM weighing <6 kg, while 73% of SM and 88% of
      USM in all weight-bands had evening Cmin values >8 mg/L. Cmin was not markedly
      affected by administration time, but was altered by unequal splitting of the
      daily dose. CONCLUSIONS: Diurnal variation does not greatly affect nevirapine
      exposure. However, when daily doses cannot be split equally, the larger dose
      should be given in the morning. To achieve homogeneous exposures, nevirapine
      doses for SM and USM should be reduced by 50%, and children weighing <6 kg with
      EM or IM metabolizer status should receive the same dose as children weighing 6
      10 kg.

PMID- 27707993
TI  - Short- and long-term effects of oral vancomycin on the human intestinal
      microbiota.
AB  - BACKGROUND: Oral vancomycin remains the mainstay of therapy for severe infections
      produced by Clostridium difficile, the most prevalent cause of healthcare
      associated infectious diarrhoea in developed countries. However, its short- and
      long-term effects on the human intestinal microbiota remain largely unknown.
      METHODS: We utilized high-throughput sequencing to analyse the effects of
      vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic
      cessation. The clinical relevance of the observed microbiota perturbations was
      studied in mice. RESULTS: During vancomycin therapy, most intestinal microbiota
      genera and operational taxonomic units (OTUs) were depleted in all analysed
      subjects, including all baseline OTUs from the phylum Bacteroidetes. This was
      accompanied by a vast expansion of genera associated with infections, including
      Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked
      differences in microbiota resilience were observed among subjects. While some
      individuals recovered a microbiota close to baseline composition, in others, up
      to 89% of abundant OTUs could no longer be detected. The clinical relevance of
      the observed microbiota changes was further demonstrated in mice, which developed
      analogous microbiota alterations. During vancomycin treatment, mice were highly
      susceptible to intestinal colonization by an antibiotic-resistant pathogen and,
      upon antibiotic cessation, a less-resilient microbiota allowed higher levels of
      pathogen colonization. CONCLUSIONS: Oral vancomycin induces drastic and
      consistent changes in the human intestinal microbiota. Upon vancomycin cessation,
      the microbiota recovery rate varied considerably among subjects, which could
      influence, as validated in mice, the level of susceptibility to pathogen
      intestinal colonization. Our results demonstrate the negative long-term effects
      of vancomycin, which should be considered as a fundamental aspect of the cost
      benefit equation for antibiotic prescription.

PMID- 27707996
TI  - Chemotaxis and Immunoregulatory Function of Cardiac gammadelta T Cells in
      Dystrophin-Deficient Mice.
AB  - Duchenne muscular dystrophy (DMD) is a fatal X-linked disorder caused by
      mutations in the dystrophin gene that lead to degeneration of skeletal and
      cardiac muscles and to chronic inflammation. Despite the importance of gammadelta
      T cells in many diseases, this cellular subpopulation has not been described in
      DMD patients or in mdx mice, a widely used mouse model for studying DMD.
      Therefore, in this study, we aimed to evaluate the migration of gammadelta T
      cells to the cardiac muscle of mdx mice and to characterize their phenotype and
      functional activity. We observed no migration of gammadelta T cells to skeletal
      muscles, but these cells were found in the hearts of mdx mice during the study
      period, reaching a peak in 12-wk-old mice. These cells migrate primarily owing to
      CCL2 and CCL5 chemokines produced by cardiac tissue, and they are Vgamma1+/CD27+
      and thus produce high levels of IFN-gamma. In vivo depletion of the gammadelta T
      cells revealed gammadelta T cell-dependent cardiac inflammatory immunoregulation,
      with increased numbers of CD3+CD4+, CD3+CD8+, and, in particular, F4/80+ cells in
      the heart and increased cardiac damage in mdx mice. We also observed in vitro
      that purified cardiac Gammadelta T cells are cytotoxic against adherent
      endomysial cardiac cells, mostly macrophages, but not against peritoneal cells,
      in a perforin/granzyme-dependent manner. Our present data indicate that
      gammadelta T cells exert protective effects on the hearts of mdx mice, possibly
      by selectively killing pathogenic macrophages, and this function may be important
      for the late onset of cardiac damage in DMD.

PMID- 27707998
TI  - G-CSF-Induced Suppressor IL-10+ Neutrophils Promote Regulatory T Cells That
      Inhibit Graft-Versus-Host Disease in a Long-Lasting and Specific Way.
AB  - Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic
      hematopoietic stem cell transplantation, and many efforts have been made to
      overcome this important limitation. We showed previously that G-CSF treatment
      generates low-density splenic granulocytes that inhibit experimental aGVHD. In
      this article, we show that aGVHD protection relies on incoming IL-10+ neutrophils
      from G-CSF-treated donor spleen (G-Neutrophils). These G-Neutrophils have high
      phagocytic capacity, high peroxide production, low myeloperoxidase activity, and
      low cytoplasmic granule content, which accounts for their low density.
      Furthermore, they have low expression of MHC class II, costimulatory molecules,
      and low arginase1 expression. Also, they have low IFN-gamma, IL-17F, IL-2, and IL
      12 levels, with increased IL-10 production and NO synthase 2 expression. These
      features are in accordance with the modulatory capacity of G-Neutrophils on
      regulatory T cell (Treg) generation. In vivo, CD25+ Treg depletion shortly after
      transplantation with splenic cells from G-CSF-treated donors blocks suppression
      of aGVHD, suggesting Treg involvement in the protection induced by the G
      Neutrophils. The immunocompetence and specificity of the semiallogeneic T cells,
      long-term after the bone marrow transplant using G-Neutrophils, were confirmed by
      third-party skin graft rejection; importantly, a graft-versus-leukemia assay
      showed that T cell activity was maintained, and all of the leukemic cells were
      eliminated. We conclude that G-CSF treatment generates a population of activated
      and suppressive G-Neutrophils that reduces aGVHD in an IL-10- and Treg-dependent
      manner, while maintaining immunocompetence and the graft versus leukemia effect.

PMID- 27707997
TI  - Mannan-Binding Lectin-Associated Serine Protease 1/3 Cleavage of Pro-Factor D
      into Factor D In Vivo and Attenuation of Collagen Antibody-Induced Arthritis
      through Their Targeted Inhibition by RNA Interference-Mediated Gene Silencing.
AB  - The complement system is proposed to play an important role in the pathogenesis
      of rheumatoid arthritis (RA). The complement system mannan-binding lectin
      associated serine proteases (MASP)-1/3 cleave pro-factor D (proDf; inactive) into
      Df (active), but it is unknown where this cleavage occurs and whether inhibition
      of MASP-1/3 is a relevant therapeutic strategy for RA. In the present study, we
      show that the cleavage of proDf into Df by MASP-1/3 can occur in the circulation
      and that inhibition of MASP-1/3 by gene silencing is sufficient to ameliorate
      collagen Ab-induced arthritis in mice. Specifically, to examine the cleavage of
      proDf into Df, MASP-1/3-producing Df-/- liver tissue (donor) was transplanted
      under the kidney capsule of MASP-1/3-/- (recipient) mice. Five weeks after the
      liver transplantation, cleaved Df was present in the circulation of MASP-1/3-/-
      mice. To determine the individual effects of MASP-1/3 and Df gene silencing on
      collagen Ab-induced arthritis, mice were injected with scrambled, MASP-1/3
      targeted, or Df-targeted small interfering RNAs (siRNAs). The mRNA levels for
      MASP-1 and -3 decreased in the liver to 62 and 58%, respectively, in mice
      injected with MASP-1/3 siRNAs, and Df mRNA decreased to 53% in the adipose tissue
      of mice injected with Df siRNAs; additionally, circulating MASP-1/3 and Df
      protein levels were decreased. In mice injected with both siRNAs the clinical
      disease activity, histopathologic injury scores, C3 deposition, and synovial
      macrophage/neutrophil infiltration were significantly decreased. Thus, MASP-1/3
      represent a new therapeutic target for the treatment of RA, likely through both
      direct effects on the lectin pathway and indirectly through the alternative
      pathway.

PMID- 27708001
TI  - Invited commentary on retrospective analysis of no longer performing modified
      ultrafiltration after pediatric cardiopulmonary bypass.

PMID- 27708000
TI  - Retrospective analysis of eliminating modified ultrafiltration after pediatric
      cardiopulmonary bypass.
AB  - Modified ultrafiltration (MUF) is a technique which is commonly used immediately
      post-cardiopulmonary bypass (CPB) for open heart surgery in children. There are
      many advantages of MUF, but there are also a number of less reported
      disadvantages. At our institution, after considering all of the available data, a
      decision was made to no longer perform MUF. The primary motivation being the
      simplified and miniaturized CPB circuit would reduce hemodilution, decrease our
      likelihood of reaching our transfusion trigger during CPB and, potentially,
      improve safety. This study reports the before and after data from this practice
      change. A total of 160 patients less than 8kg were studied over 38 months and
      divided into neonatal and pediatric cohorts. Parameters reported in this study
      include: demographics, hematocrit, blood product transfusion, hemostasis,
      hemodynamics and outcomes. Although retrospective, our analysis supports an
      advantage of preventing hemodilution (via circuit miniaturization) versus
      reversing hemodilution (via MUF) at our institution with the patient population
      we examined.

PMID- 27707999
TI  - A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Ig
      Sequencing Data.
AB  - Analyses of somatic hypermutation (SHM) patterns in B cell Ig sequences have
      important basic science and clinical applications, but they are often confounded
      by the intrinsic biases of SHM targeting on specific DNA motifs (i.e., hot and
      cold spots). Modeling these biases has been hindered by the difficulty in
      identifying mutated Ig sequences in vivo in the absence of selection pressures,
      which skew the observed mutation patterns. To generate a large number of
      unselected mutations, we immunized B1-8 H chain transgenic mice with nitrophenyl
      to stimulate nitrophenyl-specific lambda+ germinal center B cells and sequenced
      the unexpressed kappa L chains using next-generation methods. Most of these kappa
      sequences had out-of-frame junctions and were presumably uninfluenced by
      selection. Despite being nonfunctionally rearranged, they were targeted by SHM
      and displayed a higher mutation frequency than functional sequences. We used
      39,173 mutations to construct a quantitative SHM targeting model. The model
      showed targeting biases that were consistent with classic hot and cold spots, yet
      revealed additional highly mutable motifs. We observed comparable targeting for
      functional and nonfunctional sequences, suggesting similar biological processes
      operate at both loci. However, we observed species- and chain-specific targeting
      patterns, demonstrating the need for multiple SHM targeting models.
      Interestingly, the targeting of C/G bases and the frequency of transition
      mutations at C/G bases was higher in mice compared with humans, suggesting lower
      levels of DNA repair activity in mice. Our models of SHM targeting provide
      insights into the SHM process and support future analyses of mutation patterns.

PMID- 27708002
TI  - Retinal nerve fibre myelination.

PMID- 27708003
TI  - An evidence-based review of recent advances in therapy for heart failure with
      reduced ejection fraction (HFrEF).
AB  - An estimated 5.1 million Americans have chronic heart failure and this is
      expected to increase 25% by 2030. Heart failure is a clinical syndrome that
      evolves from either functional or structural changes to the ventricles that lead
      to filling or ejection abnormalities. Thus far, pharmacotherapy has been show to
      be beneficial in patients only with reduced ejection fraction; however, new
      therapies have been developed in hopes of reducing the burden of heart failure.
      In this review, we will discuss current pharmacotherapies recommended in American
      College of Cardiology/American Heart Association guidelines, the evidence behind
      these recommendations as well as new and emerging therapies that have been
      developed.

PMID- 27708004
TI  - A case of coarctation of the abdominal aorta and renal artery stenosis due to
      neurofibromatosis type 1.

PMID- 27708005
TI  - Leadership and the medical registrar: how can organisations support these unsung
      heroes?
AB  - Medical registrars have been described as the 'workhorses' of National Health
      Service hospitals, being at the interface of acute and chronic health services.
      They are expected to demonstrate effective leadership skills. There are concerns
      from the Royal College of Physicians that medical registrars are being
      overwhelmed and unsupported by organisations, and are struggling in their ability
      to provide safe, high-quality patient care. Junior colleagues are also being
      deterred by general medical specialties by the prospect of becoming the 'Med
      Reg'. There is a growing need to support medical registrars in several key
      aspects of training, not least medical leadership. Thus far, there has been a
      distinct disparity in the provision of medical leadership training for junior
      doctors in the UK that has adversely affected the standard of care given to
      patients. Recent landmark reviews and initiatives, principally the Medical
      Leadership Competency Framework, have raised awareness of leadership competencies
      for all doctors and the need for their incorporation into undergraduate and
      postgraduate curricula. It is hoped that interactive strategies to engage medical
      registrars in leadership training will lead to positive results including
      improvements in interdisciplinary communication, patient outcomes and fulfilment
      of curriculum competencies. Organisations have a duty to improve the quality of
      medical leadership training so that doctors feel equipped to influence change
      throughout their careers and be tomorrow's leaders. This review outlines the
      deficiencies in training, the importance of developing leadership skills in
      medical registrars and educational strategies that could be implemented by
      organisations in a cost-effective manner.

PMID- 27708006
TI  - Large right atrial pacemaker lead thrombus diagnosed by chest CT angiography.

PMID- 27708007
TI  - The Physiology of Early Goal-Directed Therapy for Sepsis.
AB  - In 2001, Rivers and colleagues published a randomized controlled trial of early
      goal-directed therapy (EGDT) for the treatment of sepsis. More than a decade
      later, it remains a landmark achievement. The study proved the benefits of early
      aggressive treatment of sepsis. However, many questions remain about specific
      aspects of the complex EGDT algorithm. Recently, 3 large trials attempted to
      replicate these results. None of the studies demonstrated a benefit of an EGDT
      protocol for sepsis. This review explores the physiologic basis of goal-directed
      therapy, including the hemodynamic targets and the therapeutic interventions. An
      understanding of the physiologic basis of EGDT helps reconcile the results of the
      clinical trials.

PMID- 27708009
TI  - Erratum for the Technical Comment "Comment on 'Principles of connectivity among
      morphologically defined cell types in adult neocortex'" by A. L. Barth, A.
      Burkhalter, E. M. Callaway, B. W. Connors, B. Cauli, J. DeFelipe, D. Feldmeyer,
      T. Freund, Y. Kawaguchi, Z. Kisvarday, Y. Kubota, C. McBain, M. Oberlaender, J.
      Rossier, B. Rudy, J. F. Staiger, P. Somogyi, G. Tamas, R. Yuste.

PMID- 27708010
TI  - Atomic electron tomography: 3D structures without crystals.
AB  - Crystallography has been fundamental to the development of many fields of science
      over the last century. However, much of our modern science and technology relies
      on materials with defects and disorders, and their three-dimensional (3D) atomic
      structures are not accessible to crystallography. One method capable of
      addressing this major challenge is atomic electron tomography. By combining
      advanced electron microscopes and detectors with powerful data analysis and
      tomographic reconstruction algorithms, it is now possible to determine the 3D
      atomic structure of crystal defects such as grain boundaries, stacking faults,
      dislocations, and point defects, as well as to precisely localize the 3D
      coordinates of individual atoms in materials without assuming crystallinity. Here
      we review the recent advances and the interdisciplinary science enabled by this
      methodology. We also outline further research needed for atomic electron
      tomography to address long-standing unresolved problems in the physical sciences.

PMID- 27708012
TI  - Speaking of insects....

PMID- 27708014
TI  - The Subduction Zone Observatory takes shape.

PMID- 27708011
TI  - RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in
      bacteria.
AB  - In vitro, some RNAs can form stable four-stranded structures known as G
      quadruplexes. Although RNA G-quadruplexes have been implicated in
      posttranscriptional gene regulation and diseases, direct evidence for their
      formation in cells has been lacking. Here, we identified thousands of mammalian
      RNA regions that can fold into G-quadruplexes in vitro, but in contrast to
      previous assumptions, these regions were overwhelmingly unfolded in cells. Model
      RNA G-quadruplexes that were unfolded in eukaryotic cells were folded when
      ectopically expressed in Escherichia coli; however, they impaired translation and
      growth, which helps explain why we detected few G-quadruplex-forming regions in
      bacterial transcriptomes. Our results suggest that eukaryotes have a robust
      machinery that globally unfolds RNA G-quadruplexes, whereas some bacteria have
      instead undergone evolutionary depletion of G-quadruplex-forming sequences.

PMID- 27708008
TI  - A global genetic interaction network maps a wiring diagram of cellular function.
AB  - We generated a global genetic interaction network for Saccharomyces cerevisiae,
      constructing more than 23 million double mutants, identifying about 550,000
      negative and about 350,000 positive genetic interactions. This comprehensive
      network maps genetic interactions for essential gene pairs, highlighting
      essential genes as densely connected hubs. Genetic interaction profiles enabled
      assembly of a hierarchical model of cell function, including modules
      corresponding to protein complexes and pathways, biological processes, and
      cellular compartments. Negative interactions connected functionally related
      genes, mapped core bioprocesses, and identified pleiotropic genes, whereas
      positive interactions often mapped general regulatory connections among gene
      pairs, rather than shared functionality. The global network illustrates how
      coherent sets of genetic interactions connect protein complex and pathway modules
      to map a functional wiring diagram of the cell.

PMID- 27708015
TI  - Using DNA, radiation therapy gets personal.

PMID- 27708016
TI  - Neandertals made jewelry, proteins confirm.

PMID- 27708017
TI  - Paired stars sculpt nebulae into fanciful shapes.

PMID- 27708018
TI  - Aborigines and Eurasians rode one migration wave.

PMID- 27708019
TI  - China bets big on big facilities.

PMID- 27708020
TI  - Tall timber.

PMID- 27708021
TI  - Solving Australia's language puzzle.

PMID- 27708022
TI  - Gathering lots of data on a small budget.

PMID- 27708023
TI  - How conifers adapt to the cold.

PMID- 27708024
TI  - Cool by neuronal decision.

PMID- 27708025
TI  - How hybrid perovskites get their groove.

PMID- 27708026
TI  - From science to service.

PMID- 27708027
TI  - Toward strategic, coherent, policy-relevant arctic science.

PMID- 27708028
TI  - Compound hazards yield Louisiana flood.

PMID- 27708029
TI  - Addressing obesity in homeless children.

PMID- 27708030
TI  - Zika vaccine: Clinical trial and error?

PMID- 27708032
TI  - Tomography reveals buoyant asthenosphere accumulating beneath the Juan de Fuca
      plate.
AB  - The boundary between Earth's strong lithospheric plates and the underlying mantle
      asthenosphere corresponds to an abrupt seismic velocity decrease and electrical
      conductivity increase with depth, perhaps indicating a thin, weak layer that may
      strongly influence plate motion dynamics. The behavior of such a layer at
      subduction zones remains unexplored. We present a tomographic model, derived from
      on- and offshore seismic experiments, that reveals a strong low-velocity feature
      beneath the subducting Juan de Fuca slab along the entire Cascadia subduction
      zone. Through simple geodynamic arguments, we propose that this low-velocity
      feature is the accumulation of material from a thin, weak, buoyant layer present
      beneath the entire oceanic lithosphere. The presence of this feature could have
      major implications for our understanding of the asthenosphere and subduction zone
      dynamics.

PMID- 27708033
TI  - Screening in crystalline liquids protects energetic carriers in hybrid
      perovskites.
AB  - Hybrid lead halide perovskites exhibit carrier properties that resemble those of
      pristine nonpolar semiconductors despite static and dynamic disorder, but how
      carriers are protected from efficient scattering with charged defects and optical
      phonons is unknown. Here, we reveal the carrier protection mechanism by comparing
      three single-crystal lead bromide perovskites: CH3NH3PbBr3, CH(NH2)2PbBr3, and
      CsPbBr3 We observed hot fluorescence emission from energetic carriers with ~102
      picosecond lifetimes in CH3NH3PbBr3 or CH(NH2)2PbBr3, but not in CsPbBr3 The hot
      fluorescence is correlated with liquid-like molecular reorientational motions,
      suggesting that dynamic screening protects energetic carriers via solvation or
      large polaron formation on time scales competitive with that of ultrafast
      cooling. Similar protections likely exist for band-edge carriers. The long-lived
      energetic carriers may enable hot-carrier solar cells with efficiencies exceeding
      the Shockley-Queisser limit.

PMID- 27708034
TI  - High-quality graphene via microwave reduction of solution-exfoliated graphene
      oxide.
AB  - Efficient exfoliation of graphite in solutions to obtain high-quality graphene
      flakes is desirable for printable electronics, catalysis, energy storage, and
      composites. Graphite oxide with large lateral dimensions has an exfoliation yield
      of ~100%, but it has not been possible to completely remove the oxygen functional
      groups so that the reduced form of graphene oxide (GO; reduced form: rGO) remains
      a highly disordered material. Here we report a simple, rapid method to reduce GO
      into pristine graphene using 1- to 2-second pulses of microwaves. The desirable
      structural properties are translated into mobility values of >1000 square
      centimeters per volt per second in field-effect transistors with microwave
      reduced GO (MW-rGO) as the channel material and into particularly high activity
      for MW-rGO catalyst support toward oxygen evolution reactions.

PMID- 27708031
TI  - Plant diversity patterns in neotropical dry forests and their conservation
      implications.
AB  - Seasonally dry tropical forests are distributed across Latin America and the
      Caribbean and are highly threatened, with less than 10% of their original extent
      remaining in many countries. Using 835 inventories covering 4660 species of woody
      plants, we show marked floristic turnover among inventories and regions, which
      may be higher than in other neotropical biomes, such as savanna. Such high
      floristic turnover indicates that numerous conservation areas across many
      countries will be needed to protect the full diversity of tropical dry forests.
      Our results provide a scientific framework within which national decision-makers
      can contextualize the floristic significance of their dry forest at a regional
      and continental scale.

PMID- 27708035
TI  - Surface uplift and time-dependent seismic hazard due to fluid injection in
      eastern Texas.
AB  - Observations that unequivocally link seismicity and wastewater injection are
      scarce. Here we show that wastewater injection in eastern Texas causes uplift,
      detectable in radar interferometric data up to >8 kilometers from the wells.
      Using measurements of uplift, reported injection data, and a poroelastic model,
      we computed the crustal strain and pore pressure. We infer that an increase of >1
      megapascal in pore pressure in rocks with low compressibility triggers
      earthquakes, including the 4.8-moment magnitude event that occurred on 17 May
      2012, the largest earthquake recorded in eastern Texas. Seismic activity
      increased even while injection rates declined, owing to diffusion of pore
      pressure from earlier periods with higher injection rates. Induced seismicity
      potential is suppressed where tight confining formations prevent pore pressure
      from propagating into crystalline basement rocks.

PMID- 27708036
TI  - Radiocarbon constraints imply reduced carbon uptake by soils during the 21st
      century.
AB  - Soil is the largest terrestrial carbon reservoir and may influence the sign and
      magnitude of carbon cycle-climate feedbacks. Many Earth system models (ESMs)
      estimate a significant soil carbon sink by 2100, yet the underlying carbon
      dynamics determining this response have not been systematically tested against
      observations. We used 14C data from 157 globally distributed soil profiles
      sampled to 1-meter depth to show that ESMs underestimated the mean age of soil
      carbon by a factor of more than six (430 +/- 50 years versus 3100 +/- 1800
      years). Consequently, ESMs overestimated the carbon sequestration potential of
      soils by a factor of nearly two (40 +/- 27%). These inconsistencies suggest that
      ESMs must better represent carbon stabilization processes and the turnover time
      of slow and passive reservoirs when simulating future atmospheric carbon dioxide
      dynamics.

PMID- 27708037
TI  - A Pleistocene ice core record of atmospheric O2 concentrations.
AB  - The history of atmospheric O2 partial pressures (Po2) is inextricably linked to
      the coevolution of life and Earth's biogeochemical cycles. Reconstructions of
      past Po2 rely on models and proxies but often markedly disagree. We present a
      record of Po2 reconstructed using O2/N2 ratios from ancient air trapped in ice.
      This record indicates that Po2 declined by 7 per mil (0.7%) over the past 800,000
      years, requiring that O2 sinks were ~2% larger than sources. This decline is
      consistent with changes in burial and weathering fluxes of organic carbon and
      pyrite driven by either Neogene cooling or increasing Pleistocene erosion rates.
      The 800,000-year record of steady average carbon dioxide partial pressures (Pco2)
      but declining Po2 provides distinctive evidence that a silicate weathering
      feedback stabilizes Pco2 on million-year time scales.

PMID- 27708038
TI  - Convergent local adaptation to climate in distantly related conifers.
AB  - When confronted with an adaptive challenge, such as extreme temperature, closely
      related species frequently evolve similar phenotypes using the same genes.
      Although such repeated evolution is thought to be less likely in highly polygenic
      traits and distantly related species, this has not been tested at the genome
      scale. We performed a population genomic study of convergent local adaptation
      among two distantly related species, lodgepole pine and interior spruce. We
      identified a suite of 47 genes, enriched for duplicated genes, with variants
      associated with spatial variation in temperature or cold hardiness in both
      species, providing evidence of convergent local adaptation despite 140 million
      years of separate evolution. These results show that adaptation to climate can be
      genetically constrained, with certain key genes playing nonredundant roles.

PMID- 27708040
TI  - Managing my fear of missing out.

PMID- 27708041
TI  - APS Takes a Look in the Mirror.

PMID- 27708042
TI  - Challenges, Opportunities, and the Future of Physiological Publications in the
      Hype Cycle.

PMID- 27708039
TI  - A secreted bacterial peptidoglycan hydrolase enhances tolerance to enteric
      pathogens.
AB  - The intestinal microbiome modulates host susceptibility to enteric pathogens, but
      the specific protective factors and mechanisms of individual bacterial species
      are not fully characterized. We show that secreted antigen A (SagA) from
      Enterococcus faecium is sufficient to protect Caenorhabditis elegans against
      Salmonella pathogenesis by promoting pathogen tolerance. The NlpC/p60
      peptidoglycan hydrolase activity of SagA is required and generates muramyl
      peptide fragments that are sufficient to protect C. elegans against Salmonella
      pathogenesis in a tol-1-dependent manner. SagA can also be heterologously
      expressed and secreted to improve the protective activity of probiotics against
      Salmonella pathogenesis in C. elegans and mice. Our study highlights how
      protective intestinal bacteria can modify microbial-associated molecular patterns
      to enhance pathogen tolerance.

PMID- 27708043
TI  - Integration and Inspiration: A Spartan's Take on Physiology.

PMID- 27708044
TI  - Physiology in Perspective: We Learn From Evolutionary/Comparative Physiology.

PMID- 27708046
TI  - Primate Torpor Expression: Ghost of the Climatic Past.
AB  - Torpor, the controlled depression of virtually all bodily function during scarce
      periods, was verified in primates under free-ranging conditions less than two
      decades ago. The large variety of different torpor patterns found both within and
      among closely related species is particularly remarkable. To help unravel the
      cause of these variable patterns, our review investigates primate torpor use
      within an evolutionary framework. First, we provide an overview of heterothermic
      primate species, focusing on the Malagasy lemurs, and discuss their use of daily
      torpor or hibernation in relation to habitat type and climatic conditions.
      Second, we investigate environmental characteristics that may have been involved
      in shaping the high variability of torpor expression found in lemurs today.
      Third, we examine potential triggers for torpor use in lemurs. We propose the
      "torpor refugia hypothesis" to illustrate how disparate primate torpor patterns
      possibly evolved in response to environmental cues during glacial periods, when
      animals were restricted to different refuge habitats along riverine corridors.
      For example, individuals enduring harsher conditions at higher altitudes likely
      developed seasonal hibernation, whereas those inhabiting lower elevation river
      catchments might have coped with unfavorable conditions by employing daily
      torpor. The ultimate stimuli triggering torpor use today likely differ between
      the different habitats of Madagascar. The broad diversity of torpor patterns in
      lemurs among closely related species, both within the same and in distinctly
      different habitat types, provides an ideal base for research into the stimuli for
      torpor use in endotherms in general. Our hypothesis highlights the importance of
      considering the environmental conditions under which ecosystems and species
      evolved when trying to explain physiological adaptations seen today.

PMID- 27708045
TI  - Evolutionary Medicine: The Ongoing Evolution of Human Physiology and Metabolism.
AB  - The field of evolutionary medicine uses evolutionary principles to understand
      changes in human anatomy and physiology that have occurred over time in response
      to environmental changes. Through this evolutionary-based approach, we can
      understand disease as a consequence of anatomical and physiological "trade-offs"
      that develop to facilitate survival and reproduction. We demonstrate how
      diachronic study of human anatomy and physiology is fundamental for an increased
      understanding of human health and disease.

PMID- 27708047
TI  - Physiological Challenges to Fishes in a Warmer and Acidified Future.
AB  - With the projected levels of global warming and ocean acidification, fishes have
      to face warmer waters with CO2 levels that are the highest in over 30 million
      years. The resultant rise in body temperature means that metabolic rates of fish
      will increase, and some may become energetically compromised. No less worrying,
      and maybe more surprising, is that rising CO2 concentrations appear to trigger pH
      regulatory mechanisms that disrupts neural ion gradients, leading to altered
      neurotransmitter function and maladaptive behavioral changes. We point out the
      many outstanding questions, including the ultimate one: Will fish be able to
      adapt to these challenges?

PMID- 27708048
TI  - Cephalopod Susceptibility to Asphyxiation via Ocean Incalescence, Deoxygenation,
      and Acidification.
AB  - Squids are powerful swimmers with high metabolic rates despite constrained oxygen
      uptake and transport. They have evolved novel physiological strategies for
      survival in extreme environments that provide insight into their susceptibility
      to asphyxiation under anthropogenic ocean incalescence (warming), deoxygenation,
      and acidification. Plasticity of ecological and physiological traits, in
      conjunction with vertical and latitudinal mobility, may explain their
      evolutionary persistence and ensure their future survival.

PMID- 27708049
TI  - Cardiovascular Physiology of Dinosaurs.
AB  - Cardiovascular function in dinosaurs can be inferred from fossil evidence with
      knowledge of how metabolic rate, blood flow rate, blood pressure, and heart size
      are related to body size in living animals. Skeletal stature and nutrient foramen
      size in fossil femora provide direct evidence of a high arterial blood pressure,
      a large four-chambered heart, a high aerobic metabolic rate, and intense
      locomotion. But was the heart of a huge, long-necked sauropod dinosaur able to
      pump blood up 9 m to its head?

PMID- 27708051
TI  - Improving efficiency and stability of perovskite solar cells with photocurable
      fluoropolymers.
AB  - Organometal halide perovskite solar cells have demonstrated high conversion
      efficiency but poor long-term stability against ultraviolet irradiation and
      water. We show that rapid light-induced free-radical polymerization at ambient
      temperature produces multifunctional fluorinated photopolymer coatings that
      confer luminescent and easy-cleaning features on the front side of the devices,
      while concurrently forming a strongly hydrophobic barrier toward environmental
      moisture on the back contact side. The luminescent photopolymers re-emit
      ultraviolet light in the visible range, boosting perovskite solar cells
      efficiency to nearly 19% under standard illumination. Coated devices reproducibly
      retain their full functional performance during prolonged operation, even after a
      series of severe aging tests carried out for more than 6 months.

PMID- 27708050
TI  - Breathtaking Songs: Coordinating the Neural Circuits for Breathing and Singing.
AB  - The vocal behavior of birds is remarkable for its diversity, and songs can
      feature elaborate characteristics such as long duration, rapid temporal pattern,
      and broad frequency range. The respiratory system plays a central role in
      generating the complex song patterns that must be integrated with its life
      sustaining functions. Here, we explore how precise coordination between the
      neural circuits for breathing and singing is fundamental to production of these
      remarkable behaviors.

PMID- 27708053
TI  - Incorporation of rubidium cations into perovskite solar cells improves
      photovoltaic performance.
AB  - All of the cations currently used in perovskite solar cells abide by the
      tolerance factor for incorporation into the lattice. We show that the small and
      oxidation-stable rubidium cation (Rb+) can be embedded into a "cation cascade" to
      create perovskite materials with excellent material properties. We achieved
      stabilized efficiencies of up to 21.6% (average value, 20.2%) on small areas (and
      a stabilized 19.0% on a cell 0.5 square centimeters in area) as well as an
      electroluminescence of 3.8%. The open-circuit voltage of 1.24 volts at a band gap
      of 1.63 electron volts leads to a loss in potential of 0.39 volts, versus 0.4
      volts for commercial silicon cells. Polymer-coated cells maintained 95% of their
      initial performance at 85 degrees C for 500 hours under full illumination and
      maximum power point tracking.

PMID- 27708052
TI  - A chemical biology route to site-specific authentic protein modifications.
AB  - Many essential biological processes are controlled by posttranslational protein
      modifications. The inability to synthetically attain the diversity enabled by
      these modifications limits functional studies of many proteins. We designed a
      three-step approach for installing authentic posttranslational modifications in
      recombinant proteins. We first use the established O-phosphoserine (Sep)
      orthogonal translation system to create a Sep-containing recombinant protein. The
      Sep residue is then dephosphorylated to dehydroalanine (Dha). Last, conjugate
      addition of alkyl iodides to Dha, promoted by zinc and copper, enables
      chemoselective carbon-carbon bond formation. To validate our approach, we
      produced histone H3, ubiquitin, and green fluorescent protein variants with site
      specific modifications, including different methylations of H3K79. The methylated
      histones stimulate transcription through histone acetylation. This approach
      offers a powerful tool to engineer diverse designer proteins.

PMID- 27708054
TI  - Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic
      mechanism.
AB  - Aerobic glycolysis (the Warburg effect) is a metabolic hallmark of activated T
      cells and has been implicated in augmenting effector T cell responses, including
      expression of the proinflammatory cytokine interferon-gamma (IFN-gamma), via 3'
      untranslated region (3'UTR)-mediated mechanisms. Here, we show that lactate
      dehydrogenase A (LDHA) is induced in activated T cells to support aerobic
      glycolysis but promotes IFN-gamma expression independently of its 3'UTR. Instead,
      LDHA maintains high concentrations of acetyl-coenzyme A to enhance histone
      acetylation and transcription of Ifng Ablation of LDHA in T cells protects mice
      from immunopathology triggered by excessive IFN-gamma expression or deficiency of
      regulatory T cells. These findings reveal an epigenetic mechanism by which
      aerobic glycolysis promotes effector T cell differentiation and suggest that LDHA
      may be targeted therapeutically in autoinflammatory diseases.

PMID- 27708055
TI  - A selective insecticidal protein from Pseudomonas for controlling corn rootworms.
AB  - The coleopteran insect western corn rootworm (WCR) (Diabrotica virgifera
      virgifera LeConte) is a devastating crop pest in North America and Europe.
      Although crop plants that produce Bacillus thuringiensis (Bt) proteins can limit
      insect infestation, some insect populations have evolved resistance to Bt
      proteins. Here we describe an insecticidal protein, designated IPD072Aa, that is
      isolated from Pseudomonas chlororaphis. Transgenic corn plants expressing
      IPD072Aa show protection from WCR insect injury under field conditions. IPD072Aa
      leaves several lepidopteran and hemipteran insect species unaffected but is
      effective in killing WCR larvae that are resistant to Bt proteins produced by
      currently available transgenic corn. IPD072Aa can be used to protect corn crops
      against WCRs.

PMID- 27708056
TI  - Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2.
AB  - RyR2 is a high-conductance intracellular calcium (Ca2+) channel that controls the
      release of Ca2+ from the sarco(endo)plasmic reticulum of a variety of cells.
      Here, we report the structures of RyR2 from porcine heart in both the open and
      closed states at near-atomic resolutions determined using single-particle
      electron cryomicroscopy. Structural comparison reveals a breathing motion of the
      overall cytoplasmic region resulted from the interdomain movements of amino
      terminal domains (NTDs), Helical domains, and Handle domains, whereas almost no
      intradomain shifts are observed in these armadillo repeats-containing domains.
      Outward rotations of the Central domains, which integrate the conformational
      changes of the cytoplasmic region, lead to the dilation of the cytoplasmic gate
      through coupled motions. Our structural and mutational characterizations provide
      important insights into the gating and disease mechanism of RyRs.

PMID- 27708057
TI  - Systematic mapping of functional enhancer-promoter connections with CRISPR
      interference.
AB  - Gene expression in mammals is regulated by noncoding elements that can affect
      physiology and disease, yet the functions and target genes of most noncoding
      elements remain unknown. We present a high-throughput approach that uses
      clustered regularly interspaced short palindromic repeats (CRISPR) interference
      (CRISPRi) to discover regulatory elements and identify their target genes. We
      assess >1 megabase of sequence in the vicinity of two essential transcription
      factors, MYC and GATA1, and identify nine distal enhancers that control gene
      expression and cellular proliferation. Quantitative features of chromatin state
      and chromosome conformation distinguish the seven enhancers that regulate MYC
      from other elements that do not, suggesting a strategy for predicting enhancer
      promoter connectivity. This CRISPRi-based approach can be applied to dissect
      transcriptional networks and interpret the contributions of noncoding genetic
      variation to human disease.

PMID- 27708059
TI  - Posttranslational mutagenesis: A chemical strategy for exploring protein side
      chain diversity.
AB  - Posttranslational modification of proteins expands their structural and
      functional capabilities beyond those directly specified by the genetic code.
      However, the vast diversity of chemically plausible (including unnatural but
      functionally relevant) side chains is not readily accessible. We describe C (sp3)
      C (sp3) bond-forming reactions on proteins under biocompatible conditions, which
      exploit unusual carbon free-radical chemistry, and use them to form Cbeta-Cgamma
      bonds with altered side chains. We demonstrate how these transformations enable a
      wide diversity of natural, unnatural, posttranslationally modified (methylated,
      glycosylated, phosphorylated, hydroxylated), and labeled (fluorinated,
      isotopically labeled) side chains to be added to a common, readily accessible
      dehydroalanine precursor in a range of representative protein types and
      scaffolds. This approach, outside of the rigid constraints of the ribosome and
      enzymatic processing, may be modified more generally for access to diverse
      proteins.

PMID- 27708058
TI  - Rapid development of a DNA vaccine for Zika virus.
AB  - Zika virus (ZIKV) was identified as a cause of congenital disease during the
      explosive outbreak in the Americas and Caribbean that began in 2015. Because of
      the ongoing fetal risk from endemic disease and travel-related exposures, a
      vaccine to prevent viremia in women of childbearing age and their partners is
      imperative. We found that vaccination with DNA expressing the premembrane and
      envelope proteins of ZIKV was immunogenic in mice and nonhuman primates, and
      protection against viremia after ZIKV challenge correlated with serum
      neutralizing activity. These data not only indicate that DNA vaccination could be
      a successful approach to protect against ZIKV infection, but also suggest a
      protective threshold of vaccine-induced neutralizing activity that prevents
      viremia after acute infection.

PMID- 27708061
TI  - A Value Analysis of Lean Processes in Target Value Design and Integrated Project
      Delivery.
AB  - OBJECTIVE: To investigate what key stakeholders consider to be the advantages and
      the opportunities for improvement in using lean thinking and tools in the
      integrated project delivery (IPD) process. METHOD: A detailed literature review
      was followed by case study of a Lean-IPD project. Interviews with members of the
      project leadership team, focus groups with the integrated team as well as the
      design team, and an online survey of all stakeholders were conducted. ANALYSIS:
      Statistical analysis and thematic content analysis were used to analyze the data,
      followed by a plus-delta analysis. RESULTS: (1) Learning is a large, implicit
      benefit of Lean-IPD that is not currently captured by any success metric; (2) the
      cardboard mock-up was the most successful lean strategy; (3) although a
      collaborative project, the level of influence of different stakeholder groups was
      perceived to be different by different stakeholders; (4) overall, Lean-IPD was
      rated as better than traditional design-bid-build methods; and (5) opportunities
      for improvement reported were increase in accurate cost estimating, more
      efficient use of time, perception of imbalance of control/influence, and need for
      facilitation (which represents different points of view). CONCLUSION: While lean
      tools and an IPD method are preferred to traditional design-bid-build methods,
      the perception of different stakeholders varies and more work needs to be done to
      allow a truly shared decision-making model. Learning was identified as one of the
      biggest advantages.

PMID- 27708060
TI  - How economic, humanitarian, and religious concerns shape European attitudes
      toward asylum seekers.
AB  - What types of asylum seekers are Europeans willing to accept? We conducted a
      conjoint experiment asking 18,000 eligible voters in 15 European countries to
      evaluate 180,000 profiles of asylum seekers that randomly varied on nine
      attributes. Asylum seekers who have higher employability, have more consistent
      asylum testimonies and severe vulnerabilities, and are Christian rather than
      Muslim received the greatest public support. These results suggest that public
      preferences over asylum seekers are shaped by sociotropic evaluations of their
      potential economic contributions, humanitarian concerns about the deservingness
      of their claims, and anti-Muslim bias. These preferences are similar across
      respondents of different ages, education levels, incomes, and political
      ideologies, as well as across the surveyed countries. This public consensus on
      what types of asylum seekers to accept has important implications for theory and
      policy.

PMID- 27708062
TI  - Homoharringtonine (omacetaxine mepesuccinate) as an adjunct for FLT3-ITD acute
      myeloid leukemia.
AB  - An in vitro drug-screening platform on patient samples was developed and
      validated to design personalized treatment for relapsed/refractory acute myeloid
      leukemia (AML). Unbiased clustering and correlation showed that homoharringtonine
      (HHT), also known as omacetaxine mepesuccinate, exhibited preferential
      antileukemia effect against AML carrying internal tandem duplication of fms-like
      tyrosine kinase 3 (FLT3-ITD). It worked synergistically with FLT3 inhibitors to
      suppress leukemia growth in vitro and in xenograft mouse models. Mechanistically,
      the effect was mediated by protein synthesis inhibition and reduction of short
      lived proteins, including total and phosphorylated forms of FLT3 and its
      downstream signaling proteins. A phase 2 clinical trial of sorafenib and HHT
      combination treatment in FLT3-ITD AML patients resulted in complete remission
      (true or with insufficient hematological recovery) in 20 of 24 patients (83.3%),
      reduction of ITD allelic burden, and median leukemia-free and overall survivals
      of 12 and 33 weeks. The regimen has successfully bridged five patients to
      allogeneic hematopoietic stem cell transplantation and was well tolerated in
      patients unfit for conventional chemotherapy, including elderly and heavily
      pretreated patients. This study validated the principle and clinical relevance of
      in vitro drug testing and identified an improved treatment for FLT3-ITD AML. The
      results provided the foundation for phase 2/3 clinical trials to ascertain the
      clinical efficacy of FLT3 inhibitors and HHT in combination.

PMID- 27708063
TI  - Mechanistic modeling of hemoglobin glycation and red blood cell kinetics enables
      personalized diabetes monitoring.
AB  - The amount of glycated hemoglobin (HbA1c) in diabetic patients' blood provides
      the best estimate of the average blood glucose concentration over the preceding 2
      to 3 months. It is therefore essential for disease management and is the best
      predictor of disease complications. Nevertheless, substantial unexplained glucose
      independent variation in HbA1c makes its reflection of average glucose inaccurate
      and limits the precision of medical care for diabetics. The true average glucose
      concentration of a nondiabetic and a poorly controlled diabetic may differ by
      less than 15 mg/dl, but patients with identical HbA1c values may have true
      average glucose concentrations that differ by more than 60 mg/dl. We combined a
      mechanistic mathematical model of hemoglobin glycation and red blood cell
      kinetics with large sets of within-patient glucose measurements to derive patient
      specific estimates of nonglycemic determinants of HbA1c, including mean red blood
      cell age. We found that between-patient variation in derived mean red blood cell
      age explains all glucose-independent variation in HbA1c. We then used our model
      to personalize prospective estimates of average glucose and reduced errors by
      more than 50% in four independent groups of greater than 200 patients. The
      current standard of care provided average glucose estimates with errors >15 mg/dl
      for one in three patients. Our patient-specific method reduced this error rate to
      1 in 10. Our personalized approach should improve medical care for diabetes using
      existing clinical measurements.

PMID- 27708064
TI  - Birefringence microscopy platform for assessing airway smooth muscle structure
      and function in vivo.
AB  - The inability to visualize airway smooth muscle (ASM) cells in vivo is a major
      obstacle in understanding their role in normal physiology and diseases. At
      present, there is no imaging modality available to assess ASM in vivo. Confocal
      endomicroscopy lacks the penetration depth and field of view, and conventional
      optical coherence tomography (OCT) does not have sufficient contrast to
      differentiate ASM from surrounding tissues. We have developed a birefringence
      microscopy platform that leverages the micro-organization of tissue to add
      further dimension to traditional OCT. We have used this technology to validate
      ASM measurements in ex vivo swine and canine studies, visualize and characterize
      volumetric representations of ASM in vivo, and quantify and predict ASM
      contractile force as a function of optical retardation. We provide in vivo images
      and volumetric assessments of ASM in living humans and document structural
      disease variations in subjects with mild asthma. The opportunity to link
      inflammatory responses to ASM responses and to link ASM responses to clinical
      responses and outcomes could lead to an increased understanding of diseases of
      the airway and, ultimately, to improved patient outcomes.

PMID- 27708067
TI  - Feasibility and Reliability of the System for Observing Play and Leisure Activity
      in Youth (SOPLAY) for Measuring Moderate to Vigorous Physical Activity in
      Children Visiting an Interactive Children's Museum Exhibition.
AB  - PURPOSE: To test the feasibility and reliability of a direct observation method
      for measuring moderate to vigorous physical activity (MVPA) in children visiting
      an interactive children's museum exhibition. DESIGN: Direct observation was used
      to assess MVPA in children visiting an interactive children's museum exhibition
      on 2 weekend days in winter 2013. SETTING: The Children's Museum of Manhattan's
      EatSleepPlayTM: Building Health Every Day exhibition. PARTICIPANTS: Children
      (group level) visiting the museum exhibition. MEASURES: System for Observing Play
      and Leisure Activity in Youth (SOPLAY). ANALYSES: Interobserver reliability was
      analyzed for MVPA and activity type. Two-group analyses were conducted using a
      series of Wilcoxon rank sum tests. RESULTS: A total of 545 children were observed
      over 288 observations. No significant differences were found between observers
      for MVPA ( r = .91, P = .6804) or activity type (kappa = .90, P = .6334).
      Children participated in MVPA during 35.2% of all observations. No significant
      differences were found for participation in MVPA between boys (37.6%) and girls
      (32.8%, P = .1589). CONCLUSION: The SOPLAY may be a useful tool for measuring
      MVPA in interactive children's museum exhibitions. Research with multiple museum
      settings and diverse groups of children over longer periods of time is warranted
      to further establish the feasibility and reliability of the SOPLAY for measuring
      MVPA in this novel setting.

PMID- 27708065
TI  - Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells
      and airway structural cells to type 2 inflammation.
AB  - Despite systemic sensitization, not all allergic individuals develop asthma
      symptoms upon airborne allergen exposure. Determination of the factors that lead
      to the asthma phenotype in allergic individuals could guide treatment and
      identify novel therapeutic targets. We used segmental allergen challenge of
      allergic asthmatics (AA) and allergic nonasthmatic controls (AC) to determine
      whether there are differences in the airway immune response or airway structural
      cells that could drive the development of asthma. Both groups developed prominent
      allergic airway inflammation in response to allergen. However, asthmatic subjects
      had markedly higher levels of innate type 2 receptors on allergen-specific CD4+ T
      cells recruited into the airway. There were also increased levels of type 2
      cytokines, increased total mucin, and increased mucin MUC5AC in response to
      allergen in the airways of AA subjects. Furthermore, type 2 cytokine levels
      correlated with the mucin response in AA but not AC subjects, suggesting
      differences in the airway epithelial response to inflammation. Finally, AA
      subjects had increased airway smooth muscle mass at baseline measured in vivo
      using novel orientation-resolved optical coherence tomography. Our data
      demonstrate that the development of allergic asthma is dependent on the
      responsiveness of allergen-specific CD4+ T cells to innate type 2 mediators as
      well as increased sensitivity of airway epithelial cells and smooth muscle to
      type 2 inflammation.

PMID- 27708068
TI  - Smoke-Free Men: Competing and Connecting to Quit.
AB  - PURPOSE: The purpose of this study was to explore gender-related factors that
      motivate and support men's smoking reduction and cessation to inform effective
      men-centered interventions. Approach or Design: Focus group design using a semi
      structured interview guide. SETTING: Three communities in British Columbia,
      Canada. PARTICIPANTS: A total of 56 men who currently smoked and were interested
      in reducing or quitting or had quit. INTERVENTION: N/A. METHODS: Data collected
      in 6 focus group discussions were transcribed and analyzed in accord with
      principles of thematic qualitative methods. RESULTS: We report the results across
      4 interconnected themes: (1) the fight to quit takes several rounds, (2) the
      motivation of supportive competition, (3) challenges and benefits of connecting
      with smoke-free peers, and (4) playing up the physical and financial gains.
      CONCLUSIONS: Masculine-based perspectives positioned quitting alongside fighting
      for self-control, competing, connecting, physical prowess, and having extra cash
      as motivating components of programs to engage men in efforts to be smoke-free.
      It may be worthwhile to consider the inclusion of gain-framed and benefit-focused
      messaging in programs that support men's tobacco cessation.

PMID- 27708066
TI  - Long-term renal outcome in children with OCRL mutations: retrospective analysis
      of a large international cohort.
AB  - Background: Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated
      with mutations in the OCRL gene and characterized by progressive chronic kidney
      disease (CKD). Here, we aimed to investigate the long-term renal outcome and
      identify potential determinants of CKD and its progression in children with these
      tubulopathies. Methods: Retrospective analyses were conducted of clinical and
      genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype-phenotype
      analysis, we grouped mutations according to their type and localization. To
      investigate progression of CKD we used survival analysis by Kaplan-Meier method
      using stage 3 CKD as the end-point. Results: Median estimated glomerular
      filtration rate (eGFR) was lower in the LS group compared with DD2 (58.8 versus
      87.4 mL/min/1.73 m2, P < 0.01). CKD stage II-V was found in 82% of patients, of
      these 58% and 28% had moderate-to-severe CKD in LS and DD2, respectively. Three
      patients (3%), all with LS, developed stage 5 of CKD. Survival analysis showed
      that LS was also associated with a faster CKD progression than DD2 (P < 0.01). On
      multivariate analysis, eGFR was dependent only on age (b = -0.46, P < 0.001).
      Localization, but not type of mutations, tended to correlate with eGFR. There was
      also no significant association between presence of nephrocalcinosis,
      hypercalciuria, proteinuria and number of adverse clinical events and CKD.
      Conclusions: CKD is commonly found in children with OCRL mutations. CKD
      progression was strongly related to the underlying diagnosis but did not
      associate with clinical parameters, such as nephrocalcinosis or proteinuria.

PMID- 27708069
TI  - Population-Level Measures to Predict Obesity Burden in Public Schools: Looking
      Upstream for Midstream Actions.
AB  - PURPOSE: To estimate school-level obesity burden, as reflected in prevalence of
      obesity, based on the characteristics of students' socioeconomic and geographic
      environments. DESIGN: Secondary analysis of cross-sectional data. SETTING: Public
      schools (N = 504) from 43 of 67 counties in Pennsylvania. PARTICIPANTS:
      Kindergarten through grade 12 students (N = 255 949). MEASURES: School-level
      obesity prevalence for the year 2014 was calculated from state-mandated student
      body mass index (BMI) measurements. Eighteen aggregate variables, characterizing
      schools and counties, were retrieved from federal data sources. ANALYSIS: Three
      classification variables-excess weight (BMI >= 85th percentile), obesity (BMI >=
      95th percentile), and severe obesity (BMI > 35% or 120% of 95th percentile)-each
      with 3 groups of schools (low-, average-, and high-prevalence) were created for
      discriminant function analysis, based on state mean and standard deviation of
      school distribution. Analysis tested each classification model to reveal school-
      and county-level dimensions on which school groups differed from each other.
      RESULTS: Discriminant functions for obesity, which contained school enrollment,
      percentage of students receiving free/reduced-price lunch, percentage of
      black/Hispanic students, school location (suburban/other), percentage of county
      adults with postsecondary education, and percentage of county adults with
      obesity, yielded 67.86% correct classification (highest accuracy), compared to
      34.23% schools classified by chance alone. CONCLUSION: In the absence of mandated
      student BMI screenings, the model developed in this study can be used to identify
      schools most likely to have high obesity burden and, thereafter, determine
      dissemination of enhanced resources for the implementation of proven prevention
      policies and programs.

PMID- 27708070
TI  - Time to change approach - from morphology to function and pathophysiology: The
      lesson of postoperative tricuspid regurgitation.

PMID- 27708071
TI  - An evaluation of the performance of SCORE Sweden 2015 in estimating
      cardiovascular risk: The Northern Sweden MONICA Study 1999-2014.
AB  - BACKGROUND: Risk prediction models for cardiovascular death are important for
      providing advice on lifestyle and in decision-making regarding primary preventive
      drug treatment. The latest Swedish version of the Systematic COronary Risk
      Evaluation (SCORE 2015) has yet not been tested in the population. OBJECTIVE: The
      objective of this study was to estimate the prevalence of high and very high risk
      of fatal cardiovascular disease (CVD) of the current population according to 2015
      SCORE Sweden and to evaluate the predictive accuracy of the 2003 Swedish version
      of SCORE (2003 SCORE Sweden) and 2015 SCORE Sweden in a population with declining
      CVD mortality. METHODS: We estimated the high and very high risk group for
      cardiovascular death for individuals 40-65 years of age in the 2014 Northern
      Sweden MONICA population survey excluding subjects with known diabetes or
      previous CVD (n = 813). Using the 1999 MONICA survey (n = 3347) followed up for
      10 years for CVD mortality, we assessed the calibration of both 2003 and 2015
      SCORE Sweden. RESULTS: In 2014 2.6% of the population was considered at high or
      very high risk for fatal CVD, 95% were men and 76% were in the age group 60-65
      years. Including subjects with a single markedly elevated risk factor, known
      diabetes or CVD, 12% of the population was at high or very high risk. During 10
      years of follow-up of the 1999 cohort, 34 CVD deaths (24 men and 10 women)
      occurred. The 2003 SCORE overestimated the risk of death from CVD (ratio
      predicted/observed 2.3, P < 0.001) whereas the 2015 SCORE slightly overestimated
      the number of deaths (predicted/observed 1.3, P = 0.12). The 2015 SCORE predicted
      more accurately than the 2003 SCORE the number of deaths in the different risk
      and age categories. CONCLUSION: The 2015 SCORE Sweden more adequately than 2003
      SCORE Sweden predicts the number of deaths. In 2014, the proportion of high-risk
      individuals is small in northern Sweden. The main use of 2015 SCORE Sweden would
      therefore be as an educational tool between the physician and people without
      diabetes or CVD in a consultation regarding cardiovascular risk.

PMID- 27708072
TI  - Do Villages Promote Aging in Place? Results of a Longitudinal Study.
AB  - Villages are a new, grassroots, consumer-directed model that aims to promote
      aging in place and prevent unwanted relocations for older adults. In exchange for
      a yearly membership fee, Villages provide seniors with opportunities for social
      engagement (social events and classes), civic engagement (member-to-member
      volunteer opportunities), and an array of support services. In total, 222 Village
      members were surveyed at intake and 12-month follow-up to examine changes in
      their confidence aging in place, social connectedness, and health. The strongest
      positive results were in the domain of confidence, including significantly
      greater confidence aging in place, perceived social support, and less intention
      to relocate after 1 year in the Village. As most seniors were in good health and
      well connected at the time they joined the Village, there were not improvements
      in health or social connectedness. Authors discuss the importance of longer term,
      longitudinal studies to examine the effectiveness of Villages in preventing
      institutionalization over time.

PMID- 27708073
TI  - Exploring Path Models of Disablement in Residential Care and Assisted Living
      Residents.
AB  - This study examined the relationships between individual and environmental
      factors and physical activity, and between physical activity and functional
      limitations and disability in residential care/assisted living (RC/AL) residents.
      Participants completed questionnaires and physical performance tests, and wore
      the Fitbit Motion Tracker(r) to capture physical activity. Model fit was analyzed
      using two-level path models with residents nested within RC/AL settings. Model
      parameters were estimated using the MPlus robust maximum likelihood method. A
      multilevel model with good fit (root mean square error of approximation = 0.07,
      comparative fit index [CFI] = 0.91) showed that persons with greater exercise
      self-efficacy were more physically active, and persons who were more physically
      active had better physical function and less disability. Setting-level factors
      did not significantly correlate with physical activity or disability. Although
      environmental factors may influence physical activity behavior, only individual
      factors were associated with physical activity in this sample of RC/AL residents.

PMID- 27708075
TI  - Multiprocess 3D printing for increasing component functionality.
AB  - Layer-by-layer deposition of materials to manufacture parts-better known as three
      dimensional (3D) printing or additive manufacturing-has been flourishing as a
      fabrication process in the past several years and now can create complex
      geometries for use as models, assembly fixtures, and production molds. Increasing
      interest has focused on the use of this technology for direct manufacturing of
      production parts; however, it remains generally limited to single-material
      fabrication, which can limit the end-use functionality of the fabricated
      structures. The next generation of 3D printing will entail not only the
      integration of dissimilar materials but the embedding of active components in
      order to deliver functionality that was not possible previously. Examples could
      include arbitrarily shaped electronics with integrated microfluidic thermal
      management and intelligent prostheses custom-fit to the anatomy of a specific
      patient. We review the state of the art in multiprocess (or hybrid) 3D printing,
      in which complementary processes, both novel and traditional, are combined to
      advance the future of manufacturing.

PMID- 27708074
TI  - The linker histone H1.0 generates epigenetic and functional intratumor
      heterogeneity.
AB  - Tumors comprise functionally diverse subpopulations of cells with distinct
      proliferative potential. Here, we show that dynamic epigenetic states defined by
      the linker histone H1.0 determine which cells within a tumor can sustain the long
      term cancer growth. Numerous cancer types exhibit high inter- and intratumor
      heterogeneity of H1.0, with H1.0 levels correlating with tumor differentiation
      status, patient survival, and, at the single-cell level, cancer stem cell
      markers. Silencing of H1.0 promotes maintenance of self-renewing cells by
      inducing derepression of megabase-sized gene domains harboring downstream
      effectors of oncogenic pathways. Self-renewing epigenetic states are not stable,
      and reexpression of H1.0 in subsets of tumor cells establishes transcriptional
      programs that restrict cancer cells' long-term proliferative potential and drive
      their differentiation. Our results uncover epigenetic determinants of tumor
      maintaining cells.

PMID- 27708077
TI  - News at a glance.

PMID- 27708079
TI  - Will Nobel Prize overlook LIGO's master builder?

PMID- 27708078
TI  - Deep Space Network glitches worry scientists.

PMID- 27708080
TI  - Canada aims to rewrite environmental law.

PMID- 27708076
TI  - Pathological alpha-synuclein transmission initiated by binding lymphocyte
      activation gene 3.
AB  - Emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) may
      be due to cell-to-cell transmission of misfolded preformed fibrils (PFF) of alpha
      synuclein (alpha-syn). The mechanism by which alpha-syn PFF spreads from neuron
      to neuron is not known. Here, we show that LAG3 (lymphocyte-activation gene 3)
      binds alpha-syn PFF with high affinity (dissociation constant = 77 nanomolar),
      whereas the alpha-syn monomer exhibited minimal binding. alpha-Syn-biotin PFF
      binding to LAG3 initiated alpha-syn PFF endocytosis, transmission, and toxicity.
      Lack of LAG3 substantially delayed alpha-syn PFF-induced loss of dopamine
      neurons, as well as biochemical and behavioral deficits in vivo. The
      identification of LAG3 as a receptor that binds alpha-syn PFF provides a target
      for developing therapeutics designed to slow the progression of PD and related
      alpha-synucleinopathies.

PMID- 27708081
TI  - A lifeline for Greek science-or living on borrowed time?

PMID- 27708082
TI  - Rosetta ends 2-year comet mission with final descent.

PMID- 27708083
TI  - Fossil fishes challenge 'urban legend' of evolution.

PMID- 27708084
TI  - Crime forecasters.

PMID- 27708085
TI  - The biggest ear.

PMID- 27708086
TI  - Detecting structure in a protostellar disk.

PMID- 27708087
TI  - A latitudinal gradient for genetic diversity.

PMID- 27708088
TI  - Constraining lithospheric flow.

PMID- 27708089
TI  - Social memory goes viral.

PMID- 27708090
TI  - Immune receptor for pathogenic alpha-synuclein.

PMID- 27708091
TI  - Bee happy.

PMID- 27708092
TI  - James W. Cronin (1931-2016).

PMID- 27708093
TI  - Growing pains for global monitoring of societal events.

PMID- 27708094
TI  - Scientists stand with Standing Rock.

PMID- 27708095
TI  - Build habitats, not fences, for caribou.

PMID- 27708096
TI  - Illegal wildlife trade: Look to the elephants.

PMID- 27708097
TI  - High-resolution lithosphere viscosity and dynamics revealed by magnetotelluric
      imaging.
AB  - An accurate viscosity structure is critical to truthfully modeling lithosphere
      dynamics. Here, we report an attempt to infer the effective lithospheric
      viscosity from a high-resolution magnetotelluric (MT) survey across the western
      United States. The high sensitivity of MT fields to the presence of electrically
      conductive fluids makes it a promising proxy for determining mechanical strength
      variations throughout the lithosphere. We demonstrate how a viscosity structure,
      approximated from electrical resistivity, results in a geodynamic model that
      successfully predicts short-wavelength surface topography, lithospheric
      deformation, and mantle upwelling beneath recent volcanism. We further show that
      this viscosity is physically consistent with and better constrained than that
      derived from laboratory-based rheology. We conclude that MT imaging provides a
      practical observational constraint for quantifying the dynamic evolution of the
      continental lithosphere.

PMID- 27708098
TI  - Spiral density waves in a young protoplanetary disk.
AB  - Gravitational forces are expected to excite spiral density waves in
      protoplanetary disks, disks of gas and dust orbiting young stars. However,
      previous observations that showed spiral structure were not able to probe disk
      midplanes, where most of the mass is concentrated and where planet formation
      takes place. Using the Atacama Large Millimeter/submillimeter Array, we detected
      a pair of trailing symmetric spiral arms in the protoplanetary disk surrounding
      the young star Elias 2-27. The arms extend to the disk outer regions and can be
      traced down to the midplane. These millimeter-wave observations also reveal an
      emission gap closer to the star than the spiral arms. We argue that the observed
      spirals trace shocks of spiral density waves in the midplane of this young disk.

PMID- 27708099
TI  - Electron optics with p-n junctions in ballistic graphene.
AB  - Electrons transmitted across a ballistic semiconductor junction are expected to
      undergo refraction, analogous to light rays across an optical boundary. In
      graphene, the linear dispersion and zero-gap band structure admit highly
      transparent p-n junctions by simple electrostatic gating. Here, we employ
      transverse magnetic focusing to probe the propagation of carriers across an
      electrostatically defined graphene junction. We find agreement with the predicted
      Snell's law for electrons, including the observation of both positive and
      negative refraction. Resonant transmission across the p-n junction provides a
      direct measurement of the angle-dependent transmission coefficient. Comparing
      experimental data with simulations reveals the crucial role played by the
      effective junction width, providing guidance for future device design. Our
      results pave the way for realizing electron optics based on graphene p-n
      junctions.

PMID- 27708100
TI  - Ballistic miniband conduction in a graphene superlattice.
AB  - Rational design of long-period artificial lattices yields effects unavailable in
      simple solids. The moire pattern in highly aligned graphene/hexagonal boron
      nitride (h-BN) heterostructures is a lateral superlattice with high electron
      mobility and an unusual electronic dispersion whose miniband edges and saddle
      points can be reached by electrostatic gating. We investigated the dynamics of
      electrons in moire minibands by measuring ballistic transport between adjacent
      local contacts in a magnetic field, known as the transverse electron focusing
      effect. At low temperatures, we observed caustics of skipping orbits extending
      over hundreds of superlattice periods, reversals of the cyclotron revolution for
      successive minibands, and breakdown of cyclotron motion near van Hove
      singularities. At high temperatures, electron-electron collisions suppress
      focusing. Probing such miniband conduction properties is a necessity for
      engineering novel transport behaviors in superlattice devices.

PMID- 27708101
TI  - Unexpected rewards induce dopamine-dependent positive emotion-like state changes
      in bumblebees.
AB  - Whether invertebrates exhibit positive emotion-like states and what mechanisms
      underlie such states remain poorly understood. We demonstrate that bumblebees
      exhibit dopamine-dependent positive emotion-like states across behavioral
      contexts. After training with one rewarding and one unrewarding cue, bees that
      received pretest sucrose responded in a positive manner toward ambiguous cues. In
      a second experiment, pretest consumption of sucrose solution resulted in a
      shorter time to reinitiate foraging after a simulated predator attack. These
      behavioral changes were abolished with topical application of the dopamine
      antagonist fluphenazine. Further experiments established that pretest sucrose
      does not simply cause bees to become more exploratory. Our findings present a new
      opportunity for understanding the fundamental neural elements of emotions and may
      alter the view of how emotion states affect decision-making in animals.

PMID- 27708102
TI  - An Anthropocene map of genetic diversity.
AB  - The Anthropocene is witnessing a loss of biodiversity, with well-documented
      declines in the diversity of ecosystems and species. For intraspecific genetic
      diversity, however, we lack even basic knowledge on its global distribution. We
      georeferenced 92,801 mitochondrial sequences for >4500 species of terrestrial
      mammals and amphibians, and found that genetic diversity is 27% higher in the
      tropics than in nontropical regions. Overall, habitats that are more affected by
      humans hold less genetic diversity than wilder regions, although results for
      mammals are sensitive to choice of genetic locus. Our study associates geographic
      coordinates with publicly available genetic sequences at a massive scale,
      yielding an opportunity to investigate both the drivers of this component of
      biodiversity and the genetic consequences of the anthropogenic modification of
      nature.

PMID- 27708103
TI  - Ventral CA1 neurons store social memory.
AB  - The medial temporal lobe, including the hippocampus, has been implicated in
      social memory. However, it remains unknown which parts of these brain regions and
      their circuits hold social memory. Here, we show that ventral hippocampal CA1
      (vCA1) neurons of a mouse and their projections to nucleus accumbens (NAc) shell
      play a necessary and sufficient role in social memory. Both the proportion of
      activated vCA1 cells and the strength and stability of the responding cells are
      greater in response to a familiar mouse than to a previously unencountered mouse.
      Optogenetic reactivation of vCA1 neurons that respond to the familiar mouse
      enabled memory retrieval and the association of these neurons with unconditioned
      stimuli. Thus, vCA1 neurons and their NAc shell projections are a component of
      the storage site of social memory.

PMID- 27708107
TI  - Doing science while black.

PMID- 27708106
TI  - Drosophila insulin release is triggered by adipose Stunted ligand to brain
      Methuselah receptor.
AB  - Animals adapt their growth rate and body size to available nutrients by a general
      modulation of insulin-insulin-like growth factor signaling. In Drosophila,
      dietary amino acids promote the release in the hemolymph of brain insulin-like
      peptides (Dilps), which in turn activate systemic organ growth. Dilp secretion by
      insulin-producing cells involves a relay through unknown cytokines produced by
      fat cells. Here, we identify Methuselah (Mth) as a secretin-incretin receptor
      subfamily member required in the insulin-producing cells for proper nutrient
      coupling. We further show, using genetic and ex vivo organ culture experiments,
      that the Mth ligand Stunted (Sun) is a circulating insulinotropic peptide
      produced by fat cells. Therefore, Sun and Mth define a new cross-organ circuitry
      that modulates physiological insulin levels in response to nutrients.

PMID- 27708108
TI  - Actigraphic Sleep Pattern of Preschoolers With ADHD.
AB  - OBJECTIVE: To assess the features of sleep in preschoolers with ADHD by means of
      questionnaire and actigraphy. METHOD: Twenty-five ADHD and 21 age-matched
      typically developing (TD) preschool children underwent the Child Behavior
      Checklist (CBCL) for ages 11/2 to 5 and Pre-School-Age Psychiatric Assessment
      interview. Sleep was assessed by means of a modified Sleep Disturbance Scale for
      Children and wrist actigraphy for at least 5 days. RESULTS: Children with ADHD,
      compared with TD, showed higher scores in CBCL Withdrawal (58.83 vs. 51.15, p <
      .0001), Attention Problems (69.88 vs. 51.54, p < .0001), and Aggressive Behavior
      (59.46 vs. 51.08, p < .0001) dimensions; they also showed increased actigraphic
      nocturnal activity (activity index 31.57 vs. 25.74, p < .05); and night-to-night
      variability for sleep minutes (56.44 vs. 32.79, p < .01), mean wake episodes
      (1.34 vs. 0.98, p < .05), mean activity (2.64 vs. 1.71, p < .05), and activity
      index (5.15 vs. 3.77, p < .05). CONCLUSION: This pilot study in preschoolers with
      ADHD showed increased motor activity during sleep and night-to-night variability
      for sleep duration and motor activity.

PMID- 27708104
TI  - High-resolution interrogation of functional elements in the noncoding genome.
AB  - The noncoding genome affects gene regulation and disease, yet we lack tools for
      rapid identification and manipulation of noncoding elements. We developed a
      CRISPR screen using ~18,000 single guide RNAs targeting >700 kilobases
      surrounding the genes NF1, NF2, and CUL3, which are involved in BRAF inhibitor
      resistance in melanoma. We find that noncoding locations that modulate drug
      resistance also harbor predictive hallmarks of noncoding function. With a subset
      of regions at the CUL3 locus, we demonstrate that engineered mutations alter
      transcription factor occupancy and long-range and local epigenetic environments,
      implicating these sites in gene regulation and chemotherapeutic resistance.
      Through our expansion of the potential of pooled CRISPR screens, we provide tools
      for genomic discovery and for elucidating biologically relevant mechanisms of
      gene regulation.

PMID- 27708109
TI  - Long-term clinical outcomes in patients with ST-segment elevation acute
      myocardial infarction complicated by cardiogenic shock due to acute pump failure.
AB  - BACKGROUND:: Cardiogenic shock remained the leading cause of death in ST-segment
      elevation acute myocardial infarction (STEMI) patients even in the primary
      percutaneous coronary intervention era. METHODS:: Among 3942 STEMI patients with
      primary percutaneous coronary intervention within 24 h after symptom-onset in the
      Coronary Revascularization Demonstrating Outcome Study in Kyoto acute myocardial
      infarction registry, the study population of the current analysis consisted of
      466 STEMI patients who were complicated by cardiogenic shock due to acute pump
      failure. RESULTS:: The cumulative incidence of all-cause death of cardiogenic
      shock due to acute pump failure was 25.4% at 30 days, 38.7% at one year, and
      51.4% at five years. Cumulative five-year incidence of all-cause death in
      patients with left main coronary artery culprit lesion was extremely high (left
      main coronary artery: 70.4%, left anterior descending artery: 52.5%, left
      circumflex artery: 50.6%, and right coronary artery; 44.3%, respectively, log
      rank p<0.001). The cumulative five-year incidence of all-cause death in patients
      with onset-to-balloon time ?3 h as well as those with door-to-balloon time ?90
      min were significantly lower than those without (43.3% versus 55.5%, log-rank
      p=0.008, and 44.9% versus 55.8%, log-rank p=0.003, respectively). After adjusting
      for confounders, onset-to-balloon time ?3 h and door-to-balloon time ?90 min were
      independently associated with lower long-term risk for all-cause death (hazard
      ratio: 0.69, 95% confidence interval: 0.49-0.96, p=0.03, and hazard ratio: 0.73,
      95% confidence interval: 0.53-0.98, p=0.04, respectively). CONCLUSIONS:: The long
      term mortality of STEMI patients complicated by cardiogenic shock due to acute
      pump failure remains high even in the current clinical practice. In this high
      risk category of patients, shorter onset-to-balloon and door-to-balloon time were
      associated with significantly lower long-term risk for mortality.

PMID- 27708105
TI  - Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation.
AB  - Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed
      at elevated levels from S phase until early mitosis. We found that mutant mice
      that cannot elevate cyclin A2 are chromosomally unstable and tumor-prone.
      Underlying the chromosomal instability is a failure to up-regulate the meiotic
      recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution
      of stalled replication forks, insufficient repair of double-stranded DNA breaks,
      and improper segregation of sister chromosomes. Unexpectedly, cyclin A2
      controlled Mre11 abundance through a C-terminal RNA binding domain that
      selectively and directly binds Mre11 transcripts to mediate polysome loading and
      translation. These data reveal cyclin A2 as a mechanistically diverse regulator
      of DNA replication combining multifaceted kinase-dependent functions with a
      kinase-independent, RNA binding-dependent role that ensures adequate repair of
      common replication errors.

PMID- 27708110
TI  - CHA2DS2-VASc risk factors as predictors of stroke after acute coronary syndrome:
      A systematic review and meta-analysis.
AB  - BACKGROUND: Stroke is a rare but serious complication of acute coronary syndrome.
      At present, no specific score exists to identify patients at higher risk. The aim
      of the present study is to test whether each clinical variable included in the
      CHA2DS2-VASc score retains its predictive value in patients with recent acute
      coronary syndrome, irrespective of atrial fibrillation. METHODS: The meta
      analysis was conducted according to the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in
      Epidemiology (MOOSE) guidelines. All clinical trials and observational studies
      presenting data on the association between stroke/transient ischemic attack
      incidence and at least one CHA2DS2-VASc item in patients with a recent acute
      coronary syndrome were considered in the analysis. Atrial fibrillation diagnosis
      was also considered. RESULTS: The whole cohort included 558,193 patients of which
      7108 (1.3%) had an acute stroke and/or transient ischemic attack during follow-up
      (median nine months; 1st-3rd quartile 1-12 months). Age and previous stroke had
      the highest odds ratios (odds ratio 2.60; 95% confidence interval 2.21-3.06 and
      odds ratio 2.74; 95% confidence interval 2.19-3.42 respectively), in accordance
      with the two-point value given in the CHA2DS2-VASc score. All other factors were
      positively associated with stroke, although with lower odds ratios. Atrial
      fibrillation, while present in only 11.2% of the population, confirmed its
      association with an increased risk of stroke and/or transient ischemic attack
      (odds ratio 2.04; 95% confidence interval 1.71-2.44). CONCLUSIONS: All risk
      factors included in the CHA2DS2-VASc score are associated with stroke/ transient
      ischemic attack in patients with recent acute coronary syndrome, and retain
      similar odds ratios to what already seen in atrial fibrillation. The utility of
      CHA2DS2-VASc score for risk stratification of stroke in patients with acute
      coronary syndrome remains to be determined.

PMID- 27708111
TI  - Zofenopril and ramipril in patients with left ventricular systolic dysfunction
      after acute myocardial infarction: A propensity analysis of the Survival of
      Myocardial Infarction Long-term Evaluation (SMILE) 4 study.
AB  - INTRODUCTION: This was a propensity score analysis of the prospective,
      randomized, double-blind Survival of Myocardial Infarction Long-term Evaluation
      (SMILE) 4 study in which one-year treatment with zofenopril 60 mg plus
      acetylsalicylic acid (ASA) 100 mg gave superior results compared to ramipril 10
      mg plus ASA in terms of death or hospitalization for cardiovascular causes in
      patients with acute myocardial infarction (AMI) complicated by left ventricular
      dysfunction (LVD). MATERIALS AND METHODS: A total of 716 patients of the
      intention-to-treat population were divided into homogeneous propensity quintiles
      (Q) using a logistic regression model (QI: best risk profile; QV: worst risk
      profile). RESULTS: Treatment was associated with a similar low rate of major
      cardiovascular events in any Q. However, the efficacy of zofenopril was better
      than that of ramipril in QII, QV, and particularly QIII (odds ratio (OR) and 95%
      confidence interval: 0.43 (0.21-0.87), p<0.05]. This result was primarily
      attributed to a decrease in the risk of cardiovascular hospitalization,
      particularly striking in the QIII (OR: 0.40, 0.19-0.85; p<0.05). Mortality rate
      did not significantly differ between the two treatments in any Q. CONCLUSIONS: In
      the SMILE-4 study the propensity analysis confirmed the efficacy of zofenopril in
      the prevention of long-term cardiovascular outcomes irrespective of the
      cardiovascular risk profile of post-AMI patients.

PMID- 27708112
TI  - Unexpected Geographic Variability of the Free Running Period in the Linden Bug
      Pyrrhocoris apterus.
AB  - Circadian clocks keep organisms in synchrony with external day-night cycles. The
      free running period (FRP) of the clock, however, is usually only close to-not
      exactly-24 h. Here, we explored the geographical variation in the FRP of the
      linden bug, Pyrrhocoris apterus, in 59 field-lines originating from a wide
      variety of localities representing geographically different environments. We have
      identified a remarkable range in the FRPs between field-lines, with the fastest
      clock at ~21 h and the slowest close to 28 h, a range comparable to the
      collections of clock mutants in model organisms. Similarly, field-lines differed
      in the percentage of rhythmic individuals, with a minimum of 13.8% and a maximum
      of 86.8%. Although the FRP correlates with the latitude and perhaps with the
      altitude of the locality, the actual function of this FRP diversity is currently
      unclear. With the recent technological progress of massive parallel sequencing
      and genome editing, we can expect remarkable progress in elucidating the genetic
      basis of similar geographic variants in P. apterus or in similar emerging model
      species of chronobiology.

PMID- 27708113
TI  - Effectiveness of a brief community outreach tobacco cessation intervention in
      India: a cluster-randomised controlled trial (the BABEX Trial).
AB  - BACKGROUND: Tobacco use kills half a million people every month, most in low
      middle income countries (LMICs). There is an urgent need to identify potentially
      low-cost, scalable tobacco cessation interventions for these countries.
      OBJECTIVE: To evaluate a brief community outreach intervention delivered by
      health workers to promote tobacco cessation in India. DESIGN: Cluster-randomised
      controlled trial. SETTING: 32 low-income administrative blocks in Delhi, half
      government authorised ('resettlement colony') and half unauthorised ('J.J.
      cluster') communities. PARTICIPANTS: 1213 adult tobacco users. INTERVENTIONS:
      Administrative blocks were computer randomised in a 1:1 ratio, to the
      intervention (16 clusters; n=611) or control treatment (16 clusters; n=602),
      delivered and assessed at individual level between 07/2012 and 11/2013. The
      intervention was single session quit advice (15 min) plus a single training
      session in yogic breathing exercises; the control condition comprised very brief
      quit advice (1 min) alone. Both were delivered via outreach, with contact made
      though household visits. MEASUREMENTS: The primary outcome was 6-month sustained
      abstinence from all tobacco, assessed 7 months post intervention delivery,
      biochemically verified with salivary cotinine. RESULTS: The smoking cessation
      rate was higher in the intervention group (2.6% (16/611)) than in the control
      group (0.5% (3/602)) (relative risk=5.32, 95% CI 1.43 to 19.74, p=0.013). There
      was no interaction with type of tobacco use (smoked vs smokeless). Results did
      not change materially in adjusted analyses, controlling for participant
      characteristics. CONCLUSIONS: A single session community outreach intervention
      can increase tobacco cessation in LMIC. The effect size, while small, could
      impact public health if scaled up with high coverage. TRIAL REGISTRATION NUMBER:
      ISRCTCN23362894.

PMID- 27708116
TI  - ADHD medication prescription: Effects of child, sibling, parent and general
      practice characteristics.
AB  - Many children receive attention-deficit hyperactivity disorder (ADHD) medication,
      but factors that determine medication prescription are largely unknown. This
      study aimed to determine the relative impact of factors on the child, family and
      general practitioner (GP) practice level on ADHD medication prescription. We
      included 1259 Dutch children aged 6-18 years with a diagnostic code of ADHD or
      related behavioural problems (ICPC codes P20-P22) in NIVEL primary care database.
      Using multilevel analyses, we examined predictors of ADHD medication
      prescription. Children diagnosed as 'hyperactive' were 16 times more likely to be
      prescribed ADHD medication than those with 'behavioural concerns'. Children with
      a parent or sibling receiving ADHD medication were three to four times more
      likely to be prescribed ADHD medication themselves. Children from GP practices
      with a high percentage of children with ADHD were twice as likely to be
      prescribed ADHD medication. Concluding, factors on the individual, family and GP
      practice level determine ADHD medication prescription. Future research into the
      decision-making process for ADHD medication is warranted.

PMID- 27708114
TI  - Effect of statins on disease-related outcomes in patients with idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: Data are conflicting regarding the possible effects of statins in
      patients with idiopathic pulmonary fibrosis (IPF). This post hoc analysis
      assessed the effects of statin therapy on disease-related outcomes in IPF.
      METHODS: Patients randomised to placebo (n=624) in three controlled trials of
      pirfenidone in IPF (CAPACITY 004 and 006, ASCEND) were categorised by baseline
      statin use. Outcomes assessed during the 1-year follow-up included disease
      progression, mortality, hospitalisation and composite outcomes of death or >=10%
      absolute decline in FVC and death or >=50 m decline in 6-minute walk distance
      (6MWD). RESULTS: At baseline, 276 (44%) patients were statin users versus 348
      (56%) non-users. Baseline characteristics were similar between groups, except
      statin users were older and had higher prevalence of cardiovascular disease and
      risk factors. In multivariate analyses adjusting for differences in baseline
      characteristics, statin users had lower risks of death or 6MWD decline (HR 0.69;
      95% CI 0.48 to 0.99, p=0.0465), all-cause hospitalisation (HR 0.58; 95% CI 0.35
      to 0.94, p=0.0289), respiratory-related hospitalisation (HR 0.44; 95% CI 0.25 to
      0.80, p=0.0063) and IPF-related mortality (HR 0.36; 95% CI 0.14 to 0.95,
      p=0.0393) versus non-users. Non-significant treatment effects favouring statin
      use were observed for disease progression (HR 0.75; 95% CI 0.52 to 1.07,
      p=0.1135), all-cause mortality (HR 0.54; 95% CI 0.24 to 1.21, p=0.1369) and death
      or FVC decline (HR 0.71; 95% CI 0.48 to 1.07, p=0.1032). CONCLUSIONS: This post
      hoc analysis supports the hypothesis that statins may have a beneficial effect on
      clinical outcomes in IPF. Prospective clinical trials are required to validate
      these observations. TRIAL REGISTRATION NUMBERS: NCT01366209, NCT00287729 and
      NCT00287716.

PMID- 27708118
TI  - Gender Differences in the Incidence and Determinants of Components of the Frailty
      Phenotype Among Older Adults: Findings From the SABE Study.
AB  - OBJECTIVE: To analyze gender differences in incidence and determinants of the
      components of the frailty phenotype. METHOD: A total of 1,413 older adults were
      selected in 2006. To estimate the incidence of each frailty component, only
      individuals who did not exhibit a given component at baseline (independently of
      the presence of other components) were included in the study. The variables of
      interest were socioeconomic, behavioral, clinical, anthropometric factors and
      physical performance. The incidence of each component in 2010 was the outcome.
      RESULTS: Unintentional weight loss and slowness were more incident in men up to
      74 years of age. The other frailty components were more incident in women at all
      age groups, except weakness. Besides age, the determinants of incidence of the
      components of frailty were different between genders. DISCUSSION: Strategies for
      preventing or delaying the installation of frailty need to address gender
      differences, considering the greater complexity in the network determinants among
      women.

PMID- 27708117
TI  - Deflection Analysis of Different Needle Designs for Prostate Biopsy and Focal
      Therapy.
AB  - OBJECTIVE: The biopsy needles currently used were designed for a transrectal
      biopsy and are known to experience significant deflection from the point of entry
      into the gland to the needle tip. METHODS: Five designs were selected for
      testing: 18-gauge Bard, 15-gauge lancet tip needle with 12 degrees  vet-point
      cannula, and trocar tip needle with 12 degrees , 15 degrees , and 20 degrees  vet
      point cannulas. The 15-gauge needle was designed to take a variable specimen
      sample between 20 and 60 mm, whereas the Bard needle specimen bed was fixed at 20
      mm. The needles were bench tested on a spring-loaded platform and fired into
      gelatin matrix with modulus of elasticity similar to human prostate. RESULTS: The
      Bard device with lancet tip needle deflected an average of 0.9 mm (range 0.3-1.3
      mm) and 1.9 degrees  (range 0.6 degrees -2.8 degrees ). Increasing needle
      diameter from 18-gauge Bard to 15-gauge variable with the same lancet tip needle
      design resulted in an average deflection across the 3 test lengths of 0.9 mm
      (range 0-2.0 mm) and 0.9 degrees  (range 0 degrees -2.0 degrees ) with no
      significant difference. On the contrary, the use of the 3-point trocar tip
      needles with 12 degrees , 15 degrees , and 20 degrees  vet-point cannulas
      demonstrated significant reduction in the extent of deflection in both
      millimeters and degrees. There was no deflection at the 2- and 4-cm shots for
      both spring loads and preloads for the 3 vet tip angles tested. At 6 cm, the 20
      degrees  vet tip performed the best. CONCLUSION: We proposed a mechanism that
      provides more accurate prostate sampling by combining a 3-point trocar tip on the
      needle with a 20 degrees  vet tip on the cutting cannula. Using the phantom,
      mimicking prostate gland tissue density, no deflection was revealed between 20-
      and 60-mm biopsy lengths, which should permit a straight sample in the majority
      of prostate glands and improve cancer localization for focal therapy planning.

PMID- 27708115
TI  - Changing Clinician Practices and Attitudes Regarding the Use of Antiretroviral
      Therapy for HIV Treatment and Prevention.
AB  - As part of the HPTN 065 study in the Bronx, New York and Washington, the authors,
      we surveyed clinicians to assess for shifts in their practices and attitudes
      around HIV treatment and prevention. Antiretroviral therapy (ART)-prescribing
      clinicians at 39 HIV care sites were offered an anonymous Web-based survey at
      baseline (2010-2011) and at follow-up (2013). The 165 respondents at baseline and
      141 respondents at follow-up had similar characteristics-almost 60% were female,
      median age was 47 years, two-thirds were physicians, and nearly 80% were HIV
      specialists. The percentage who reported recommending ART irrespective of CD4
      count was higher at follow-up (15% versus 68%), as was the percentage who would
      initiate ART earlier for patients having unprotected sex with partners of unknown
      HIV status (64% versus 82%), and for those in HIV-discordant partnerships (75%
      versus 87%). In line with changing HIV treatment guidelines during 2010 to 2013,
      clinicians increasingly supported early ART for treatment and prevention.

PMID- 27708119
TI  - Getting Your Grumble Back.
AB  - PURPOSE OF STUDY: Viewing the surgical patient holistically within their
      environment of care, the bedside nurse is aware of the possible complication of
      postoperative paralytic ileus that can lead to patient discomfort and increased
      medical costs. Acute care nurses observed postoperative patients watching
      televised cooking shows on a consistent basis and questioned if there was a mind
      body link between bowel function and watching cooking shows. DESIGN OF STUDY: The
      study used an observational approach to examine the return of bowel sounds for
      postoperative patients. METHOD: Ninety-four patients that underwent abdominal
      surgery participated. A questionnaire was administered to capture total hours
      postsurgery of patient viewing cooking shows followed by chart review for age,
      height, weight, information specific to surgery, and documented first
      postsurgical flatus. FINDINGS: This study found that non-bariatric general
      surgery patients who watch cooking shows during hospitalization are significantly
      more likely to experience return of appetite and stomach sounds within 1 day
      postsurgery than patients who do not watch cooking shows. CONCLUSIONS: Based on
      the results of this study, the authors suggest that, when possible, patients who
      receive non-bariatric abdominal surgery be encouraged to watch cooking shows to
      experience the potential benefits such as early return of bowel functioning.

PMID- 27708120
TI  - Commercial Dairy Cow Milk microRNAs Resist Digestion under Simulated
      Gastrointestinal Tract Conditions.
AB  - BACKGROUND: MicroRNAs are small, gene-regulatory noncoding RNA species present in
      large amounts in milk, where they seem to be protected against degradative
      conditions, presumably because of their association with exosomes. OBJECTIVE: We
      monitored the relative stability of commercial dairy cow milk microRNAs during
      digestion and examined their associations with extracellular vesicles (EVs).
      METHODS: We used a computer-controlled, in vitro, gastrointestinal model TNO
      intestinal model-1 (TIM-1) and analyzed, by quantitative polymerase chain
      reaction, the concentration of 2 microRNAs within gastrointestinal tract
      compartments at different points in time. EVs within TIM-1 digested and
      nondigested samples were studied by immunoblotting, dynamic light scattering,
      quantitative polymerase chain reaction, and density measurements. RESULTS: A
      large quantity of dairy milk Bos taurus microRNA-223 (bta-miR-223) and bta-miR
      125b (~109-1010 copies/300 mL milk) withstood digestion under simulated
      gastrointestinal tract conditions, with the stomach causing the most important
      decrease in microRNA amounts. A large quantity of these 2 microRNAs (~108-109
      copies/300 mL milk) was detected in the upper small intestine compartments, which
      supports their potential bioaccessibility. A protocol optimized for the
      enrichment of dairy milk exosomes yielded a 100,000 * g pellet fraction that was
      positive for the exosomal markers tumor susceptibility gene-101 (TSG101),
      apoptosis-linked gene 2-interacting protein X (ALIX), and heat shock protein 70
      (HSP70) and containing bta-miR-223 and bta-miR-125b. This approach, based on
      successive ultracentrifugation steps, also revealed the existence of ALIX-, HSP70
      /low, and TSG101-/low EVs larger than exosomes and 2-6 times more enriched in bta
      miR-223 and bta-miR-125b (P < 0.05). CONCLUSIONS: Our findings indicate that
      commercial dairy cow milk contains numerous microRNAs that can resist digestion
      and are associated mostly with ALIX-, HSP70-/low, and TSG101-/low EVs. Our
      results support the existence of interspecies transfer of microRNAs mediated by
      milk consumption and challenge our current view of exosomes as the sole carriers
      of milk-derived microRNAs.

PMID- 27708121
TI  - Harmonization of Food-Frequency Questionnaires and Dietary Pattern Analysis in 4
      Ethnically Diverse Birth Cohorts.
AB  - BACKGROUND: Canada is an ethnically diverse nation, which introduces challenges
      for health care providers tasked with providing evidence-based dietary advice.
      OBJECTIVES: We aimed to harmonize food-frequency questionnaires (FFQs) across 4
      birth cohorts of ethnically diverse pregnant women to derive robust dietary
      patterns to investigate maternal and newborn outcomes. METHODS: The NutriGen
      Alliance comprises 4 prospective birth cohorts and includes 4880 Canadian mother
      infant pairs of predominantly white European [CHILD (Canadian Healthy Infant
      Longitudinal Development) and FAMILY (Family Atherosclerosis Monitoring In earLY
      life)], South Asian [START (SouTh Asian birth cohoRT)-Canada], or Aboriginal [ABC
      (Aboriginal Birth Cohort)] origins. CHILD used a multiethnic FFQ based on a
      previously validated instrument designed by the Fred Hutchinson Cancer Research
      Center, whereas FAMILY, START, and ABC used questionnaires specifically designed
      for use in white European, South Asian, and Aboriginal people, respectively. The
      serving sizes and consumption frequencies of individual food items within the 4
      FFQs were harmonized and aggregated into 36 common food groups. Principal
      components analysis was used to identify dietary patterns that were internally
      validated against self-reported vegetarian status and externally validated
      against a modified Alternative Healthy Eating Index (mAHEI). RESULTS: Three
      maternal dietary patterns were identified-"plant-based," "Western," and "health
      conscious"-which collectively explained 29% of the total variability in eating
      habits observed in the NutriGen Alliance. These patterns were strongly associated
      with self-reported vegetarian status (OR: 3.85; 95% CI: 3.47, 4.29; r2 = 0.30, P
      < 0.001; for a plant-based diet), and average adherence to the plant-based diet
      was higher in participants in the fourth quartile of the mAHEI than in the first
      quartile (mean difference: 46.1%; r2 = 0.81, P < 0.001). CONCLUSION: Dietary data
      collected by using FFQs from ethnically diverse pregnant women can be harmonized
      to identify common dietary patterns to investigate associations between maternal
      dietary intake and health outcomes.

PMID- 27708122
TI  - Determination of Dietary Iron Requirements by Full Expression of Iron-Containing
      Enzymes in Various Tissues of Broilers.
AB  - BACKGROUND: The current dietary iron requirement (80 mg/kg) of broilers is mainly
      based on growth, hemoglobin concentration, or hematocrit data obtained in a few
      early studies; however, expressions of iron-containing enzymes might be more
      sensitive novel criteria to evaluate dietary iron requirements. OBJECTIVE: The
      objective of this study was to determine dietary iron requirements of broilers
      for the full expression of succinate dehydrogenase (SDH), catalase, and
      cytochrome c oxidase (COX) in various tissues. METHODS: A total of 336 1-d-old
      Arbor Acres male chicks were randomly assigned to 1 of 7 treatments with 6
      replicates and fed a basal corn and soybean-meal diet (control, containing 67 mg
      Fe/kg) and the basal diet supplemented with 20, 40, 60, 80, 100, or 120 mg Fe/kg
      from FeSO4 ? 7H2O for 21 d. Regression analysis was performed to estimate the
      optimal dietary iron concentration with the use of broken-line or quadratic
      models. RESULTS: SDH activity in the liver and heart, COX and catalase activity
      in the liver, Sdh mRNA levels in the liver, and Cox mRNA levels in the liver and
      heart of broilers were affected (P < 0.027) by supplemental iron concentration,
      and increased quadratically (P < 0.004) as dietary iron concentration increased.
      Dietary iron requirements estimated on the basis of fitted broken-line or
      quadratic-curve models (P < 0.005) of the above indexes were 97-136 mg/kg.
      CONCLUSIONS: SDH activity in the liver and heart, COX and catalase activity in
      the liver, Sdh mRNA levels in the liver, and Cox mRNA levels in the liver and
      heart are, to our knowledge, new and sensitive criteria to evaluate the dietary
      iron requirements of broilers, and the dietary iron requirements would be 97-136
      mg/kg to support the full expression of the above iron-containing enzymes in
      various tissues of broiler chicks from 1 to 21 d of age, which are higher than
      the current NRC iron requirement.

PMID- 27708125
TI  - Social comparisons and long-term rehabilitation for traumatic brain injury: A
      longitudinal study.
AB  - Little is known about social influences on long-term rehabilitation outcomes for
      traumatic brain injury, particularly social comparisons (i.e. self-evaluations
      relative to others). Patients in long-term rehabilitation ( n = 31) completed
      assessments at baseline and 1 year. Self-reported social comparison orientation
      was comparable to existing samples and showed stability over 1 year; affective
      responses to comparisons (e.g. frustration) were less stable. Social comparison
      orientation and affective responses were related to baseline executive and
      psychosocial functioning ( rs = 0.34-0.53) and predicted worse impairment and
      depression at 1 year ( ds = 0.67, 1.39). Greater attention to comparisons in long
      term rehabilitation could improve outcomes.

PMID- 27708124
TI  - Role of sweet and other flavours in liking and disliking of electronic
      cigarettes.
AB  - OBJECTIVE: To examine the extent to which the perception of sweet and other
      flavours is associated with liking and disliking of flavoured electronic
      cigarettes (e-cigarettes). METHODS: 31 participants (13 females/18 males; 12
      sole/19 dual users) vaped 6 commercially available flavours of blu Tanks: Classic
      Tobacco (CT), Magnificent Menthol (MM), Cherry Crush (CC), Vivid Vanilla (VV),
      Pina Colada (PC) and Peach Schnapps (PS); all 'medium' strength, 12 mg/mL
      nicotine concentration. For each flavoured e-cigarette, participants first rated
      liking/disliking on the Labeled Hedonic Scale, followed by perceived intensities
      of sweetness, coolness, bitterness, harshness and specific flavour on the
      generalised version of the Labeled Magnitude Scale. The psychophysical testing
      was conducted individually in an environmental chamber. RESULTS: PC was perceived
      as sweetest and liked the most; CT was perceived as least sweet and liked the
      least. Across all flavours, liking was correlated with sweetness (r=0.31),
      coolness (r=0.25), bitterness (r=-0.25) and harshness (r=-0.29, all p<0.001).
      Specifically, liking was positively correlated with sweetness of PS (r=0.56,
      p=0.001) and PC (r=0.36, p=0.048); and with coolness of MM, CT and VV (r=0.41
      0.52, p<0.05). In contrast, harshness was negatively correlated with liking for
      CC, PC and PS (r=0.37-0.40, p<0.05). In a multivariate model, sweetness had the
      greatest positive impact on liking followed by coolness; harshness had the
      greatest negative impact on liking. CONCLUSIONS: Our findings indicate that
      bitterness and harshness, most likely from nicotine, have negative impacts on the
      liking of e-cigarettes, but the addition of flavourants that elicit sweetness or
      coolness generally improves liking. The results suggest that flavours play an
      important role in e-cigarette preference and most likely use.

PMID- 27708123
TI  - Association between use of flavoured tobacco products and quit behaviours:
      findings from a cross-sectional survey of US adult tobacco users.
AB  - BACKGROUND: Non-menthol characterising flavours (eg, fruit, candy) are banned in
      cigarettes, yet are still permitted in non-cigarette tobacco (NCT) products. This
      study examined associations between first use and current use of flavoured
      tobacco products, and current flavoured tobacco use and quit behaviours. METHODS:
      A nationally representative, telephone-based survey completed in 2012 by 1443 US
      adult tobacco users asked about use of 9 tobacco products: cigarettes, e
      cigarettes, cigars, cigarillos, little filtered cigars, pipes, hookah, smokeless
      tobacco and snus. Ever users reported first use of flavoured products, while
      current users also reported current flavoured product use. Current users reported
      quit attempts made in the past year. Data were weighted to reflect the US adult
      tobacco user population. Logistic regression models were used to examine
      associations between first/current flavour use and quit behaviours. RESULTS: Over
      70% of respondents reported first use of a flavoured tobacco product, while 54%
      reported current use of at least one flavoured product. Odds of current flavoured
      product use were greater among those who reported first use of a flavoured
      product (OR 14.82, 95% CI 9.96 to 22.06). First use of a flavoured product was
      associated with being a current tobacco user (OR 1.55, 95% CI 1.08 to 2.22).
      Compared to single product users, polytobacco users exhibited greater odds of
      reporting current use of flavoured products (OR 2.09, 95% CI 1.47 to 2.97). Forty
      four percent of current tobacco users reported a past-year quit attempt. Adjusted
      analyses among current NCT users of at least one flavoured tobacco product showed
      reduced odds of reporting a quit attempt. CONCLUSIONS: First use of a flavoured
      tobacco product was associated with current flavoured tobacco use and polytobacco
      use. Users of only flavoured NCT products exhibited reduced odds of reporting a
      quit attempt. Findings from this study reinforce the importance of flavoured
      product availability in the USA, which may have significant implications for
      efforts to reduce tobacco initiation and use at a population level. The
      relationship between characterising flavours and quit behaviours merits further
      exploration in longitudinal, population-based samples.

PMID- 27708126
TI  - 'It gets into your head as well as your body': The experiences of patients with
      cancer during oncology treatment with curative intent.
AB  - This study explored the psychosocial experiences of patients with cancer during
      the course of oncology treatment with curative intent. Our aim was to gather in
      depth insights into the shared elements of oncology treatment across a range of
      cancer types. A total of 10 individuals undergoing oncology treatment
      participated in semi-structured interviews. Six themes were identified using
      interpretative phenomenological analysis: diminished well-being, perceived role
      changes in intimate relationships, heightened awareness of limited time, a new
      order of priorities, taking things as they come and development of trust in
      health professionals. These themes indicate relevant areas of patients' well
      being, which might be enhanced through psychosocial support services.

PMID- 27708127
TI  - Creating Body Shapes From Verbal Descriptions by Linking Similarity Spaces.
AB  - Brief verbal descriptions of people's bodies (e.g., "curvy," "long-legged") can
      elicit vivid mental images. The ease with which these mental images are created
      belies the complexity of three-dimensional body shapes. We explored the
      relationship between body shapes and body descriptions and showed that a small
      number of words can be used to generate categorically accurate representations of
      three-dimensional bodies. The dimensions of body-shape variation that emerged in
      a language-based similarity space were related to major dimensions of variation
      computed directly from three-dimensional laser scans of 2,094 bodies. This
      relationship allowed us to generate three-dimensional models of people in the
      shape space using only their coordinates on analogous dimensions in the language
      based description space. Human descriptions of photographed bodies and their
      corresponding models matched closely. The natural mapping between the spaces
      illustrates the role of language as a concise code for body shape that captures
      perceptually salient global and local body features.

PMID- 27708128
TI  - Female advantage in verbal memory: Evidence of sex-specific cognitive reserve.
AB  - OBJECTIVE: We investigated sex differences in verbal memory across different
      levels of neural dysfunction, measured by temporal lobe glucose metabolic rates
      (TLGluMR). METHODS: Three hundred ninety controls and 672 participants with
      amnestic mild cognitive impairment (aMCI) and 254 with Alzheimer disease (AD)
      dementia from the Alzheimer's Disease Neuroimaging Initiative completed the Rey
      Auditory Verbal Learning Test (RAVLT) and [18F]-fluorodeoxyglucose-PET. Cross
      sectional analyses were conducted using linear regression to examine the sex by
      TLGluMR interaction on RAVLT performance in the overall sample and within
      diagnostic groups adjusting for age, education, and APOE epsilon4 genotype.
      RESULTS: Across groups, female sex and higher TLGluMR and their interaction were
      associated with better verbal memory (p values <= 0.005). The female advantage in
      verbal memory varied by TLGluMR such that the advantage was greatest among
      individuals with moderate to high TLGluMR and minimal or absent among individuals
      with lower TLGluMR. Diagnosis-stratified analyses revealed that this interaction
      was driven by the aMCI group (p values = 0.009). The interaction was not
      significant in control and AD dementia groups. CONCLUSIONS: Women show better
      verbal memory than men in aMCI despite similar levels of brain hypometabolism.
      The lifelong advantage that females show over males in verbal memory might
      represent a form of cognitive reserve that delays verbal memory decline until
      more advanced pathology, as indexed by TLGluMR. This issue is clinically
      important because verbal memory scores are used in diagnosing aMCI and AD
      dementia.

PMID- 27708129
TI  - Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A
      randomized trial.
AB  - OBJECTIVE: To assess whether multifocal, high-frequency repetitive transcranial
      magnetic stimulation (rTMS) of motor and prefrontal cortex benefits motor and
      mood symptoms in patients with Parkinson disease (PD). METHODS: Patients with PD
      and depression were enrolled in this multicenter, double-blind, sham-controlled,
      parallel-group study of real or realistic (electric) sham rTMS. Patients were
      randomized to 1 of 4 groups: bilateral M1 ( + sham dorsolateral prefrontal cortex
      [DLPFC]), DLPFC ( + sham M1), M1 + DLPFC, or double sham. The TMS course
      consisted of 10 daily sessions of 2,000 stimuli for the left DLPFC and 1,000
      stimuli for each M1 (50 * 4-second trains of 40 stimuli at 10 Hz). Patients were
      evaluated at baseline, at 1 week, and at 1, 3, and 6 months after treatment.
      Primary endpoints were changes in motor function assessed with the Unified
      Parkinson's Disease Rating Scale-III and in mood with the Hamilton Depression
      Rating Scale at 1 month. RESULTS: Of the 160 patients planned for recruitment, 85
      were screened, 61 were randomized, and 50 completed all study visits. Real M1
      rTMS resulted in greater improvement in motor function than sham at the primary
      endpoint (p < 0.05). There was no improvement in mood in the DLPFC group compared
      to the double-sham group, as well as no benefit to combining M1 and DLPFC
      stimulation for either motor or mood symptoms. CONCLUSIONS: In patients with PD
      with depression, M1 rTMS is an effective treatment of motor symptoms, while mood
      benefit after 2 weeks of DLPFC rTMS is not better than sham. Targeting both M1
      and DLPFC in each rTMS session showed no evidence of synergistic effects.
      CLINICALTRIALSGOV IDENTIFIER: NCT01080794. CLASSIFICATION OF EVIDENCE: This study
      provides Class I evidence that in patients with PD with depression, M1 rTMS leads
      to improvement in motor function while DLPFC rTMS does not lead to improvement in
      depression compared to sham rTMS.

PMID- 27708130
TI  - Distinct brain networks underlie cognitive dysfunction in Parkinson and Alzheimer
      diseases.
AB  - OBJECTIVE: To determine whether cognitive impairment in Parkinson disease (PD)
      and Alzheimer disease (AD) derives from the same network pathology. METHODS: We
      analyzed 18F-fluorodeoxyglucose PET scans from 40 patients with AD and 40 age
      matched healthy controls from the Alzheimer's Disease Neuroimaging Initiative and
      scanned an additional 10 patients with AD and 10 healthy controls at The
      Feinstein Institute for Medical Research to derive an AD-related metabolic
      pattern (ADRP) analogous to our previously established PD cognition-related
      pattern (PDCP) and PD motor-related pattern (PDRP). We computed individual
      subject expression values for ADRP and PDCP in 89 patients with PD and correlated
      summary scores for cognitive functioning with network expression. We also
      evaluated changes in ADRP and PDCP expression in a separate group of 15 patients
      with PD scanned serially over a 4-year period. RESULTS: Analysis revealed a
      significant AD-related metabolic topography characterized by covarying metabolic
      reductions in the hippocampus, parahippocampal gyrus, and parietal and temporal
      association regions. Expression of ADRP, but not PDCP, was elevated in both AD
      groups and correlated with worse cognitive summary scores. Patients with PD
      showed slight ADRP expression, due to topographic overlap with the network
      underlying PD motor-related pattern degeneration, but only their PDCP expression
      values increased as cognitive function and executive performance declined.
      Longitudinal data in PD disclosed an analogous dissociation of network
      expression. CONCLUSIONS: Cognitive dysfunction in PD is associated with a
      specific brain network that is largely spatially and functionally distinct from
      that seen in relation to AD.

PMID- 27708135
TI  - Hobnail Hemangioma With an Unusual Clinical Presentation.
AB  - Hobnail hemangioma, also known as targetoid hemosiderotic hemangioma, is an
      uncommon vascular proliferation that clinically presents as a small solitary red
      to purple papule or macule, located on the limbs or trunk. Multiple lesions and
      atypical locations have been described. Histopathologically, it exhibits a
      biphasic pattern, with dilated vessels in the superficial dermis and angulated
      vessels in the deeper dermis, with endothelial cells that show a hobnail
      appearance. There is controversy about the histogenetic origin of hobnail
      hemangioma, although recent studies support that it is a lymphatic malformation.
      The investigators report the case of a 41-year-old man with an irregular lesion,
      red to purple in color, with a maximum diameter of 4 cm, on the scalp. The
      location and in particular the clinical appearance are uncommon.
      Immunohistochemical analysis showed negativity for WT1 and focal positivity for
      D2-40. Clinical-pathologic correlation acquires particular importance in the case
      of lesions with atypical clinical presentation.

PMID- 27708136
TI  - Glutathione depletion activates the yeast vacuolar transient receptor potential
      channel, Yvc1p, by reversible glutathionylation of specific cysteines.
AB  - Glutathione depletion and calcium influx into the cytoplasm are two hallmarks of
      apoptosis. We have been investigating how glutathione depletion leads to
      apoptosis in yeast. We show here that glutathione depletion in yeast leads to the
      activation of two cytoplasmically inward-facing channels: the plasma membrane,
      Cch1p, and the vacuolar calcium channel, Yvc1p. Deletion of these channels
      partially rescues cells from glutathione depletion-induced cell death. Subsequent
      investigations on the Yvc1p channel, a homologue of the mammalian TRP channels,
      revealed that the channel is activated by glutathionylation. Yvc1p has nine
      cysteine residues, of which eight are located in the cytoplasmic regions and one
      on the transmembrane domain. We show that three of these cysteines, Cys-17, Cys
      79, and Cys-191, are specifically glutathionylated. Mutation of these cysteines
      to alanine leads to a loss in glutathionylation and a concomitant loss in calcium
      channel activity. We further investigated the mechanism of glutathionylation and
      demonstrate a role for the yeast glutathione S-transferase Gtt1p in
      glutathionylation. Yvc1p is also deglutathionylated, and this was found to be
      mediated by the yeast thioredoxin, Trx2p. A model for redox activation and
      deactivation of the yeast Yvc1p channel is presented.

PMID- 27708137
TI  - An NXF1 mRNA with a retained intron is expressed in hippocampal and neocortical
      neurons and is translated into a protein that functions as an Nxf1 cofactor.
AB  - The Nxf1 protein is a major nuclear export receptor for the transport of mRNA,
      and it also is essential for export of retroviral mRNAs with retained introns. In
      the latter case, it binds to RNA elements known as constitutive transport
      elements (CTEs) and functions in conjunction with a cofactor known as Nxt1. The
      NXF1 gene also regulates expression of its own intron-containing RNA through the
      use of a functional CTE within intron 10. mRNA containing this intron is exported
      to the cytoplasm, where it can be translated into the 356-amino acid short
      Nxf1(sNxf1) protein, despite the fact that it is a prime candidate for nonsense
      mediated decay (NMD). Here we demonstrate that sNxf1 is highly expressed in
      nuclei and dendrites of hippocampal and neocortical neurons in rodent brain.
      Additionally, we show that sNxf1 localizes in RNA granules in neurites of
      differentiated N2a mouse neuroblastoma cells, where it shows partial
      colocalization with Staufen2 isoform SS, a protein known to play a role in
      dendritic mRNA trafficking. We also show that sNxf1 forms heterodimers in
      conjunction with the full-length Nxf1 and that sNxf1 can replace Nxt1 to enhance
      the expression of CTE-containing mRNA and promote its association with
      polyribosomes.

PMID- 27708138
TI  - GOLPH3 drives cell migration by promoting Golgi reorientation and directional
      trafficking to the leading edge.
AB  - The mechanism of directional cell migration remains an important problem, with
      relevance to cancer invasion and metastasis. GOLPH3 is a common oncogenic driver
      of human cancers, and is the first oncogene that functions at the Golgi in
      trafficking to the plasma membrane. Overexpression of GOLPH3 is reported to drive
      enhanced cell migration. Here we show that the phosphatidylinositol-4
      phosphate/GOLPH3/myosin 18A/F-actin pathway that is critical for Golgi-to-plasma
      membrane trafficking is necessary and limiting for directional cell migration. By
      linking the Golgi to the actin cytoskeleton, GOLPH3 promotes reorientation of the
      Golgi toward the leading edge. GOLPH3 also promotes reorientation of lysosomes
      (but not other organelles) toward the leading edge. However, lysosome function is
      dispensable for migration and the GOLPH3 dependence of lysosome movement is
      indirect, via GOLPH3's effect on the Golgi. By driving reorientation of the Golgi
      to the leading edge and driving forward trafficking, particularly to the leading
      edge, overexpression of GOLPH3 drives trafficking to the leading edge of the
      cell, which is functionally important for directional cell migration. Our
      identification of a novel pathway for Golgi reorientation controlled by GOLPH3
      provides new insight into the mechanism of directional cell migration with
      important implications for understanding GOLPH3's role in cancer.

PMID- 27708139
TI  - Regulation of GPCR expression through an interaction with CCT7, a subunit of the
      CCT/TRiC complex.
AB  - Mechanisms that prevent aggregation and promote folding of nascent G protein
      coupled receptors (GPCRs) remain poorly understood. We identified chaperonin
      containing TCP-1 subunit eta (CCT7) as an interacting partner of the beta-isoform
      of thromboxane A2 receptor (TPbeta) by yeast two-hybrid screening. CCT7
      coimmunoprecipitated with overexpressed TPbeta and beta2-adrenergic receptor
      (beta2AR) in HEK 293 cells, but also with endogenous beta2AR. CCT7 depletion by
      small interfering RNA reduced total and cell-surface expression of both receptors
      and caused redistribution of the receptors to juxtanuclear aggresomes,
      significantly more so for TPbeta than beta2AR. Interestingly, Hsp90
      coimmunoprecipitated with beta2AR but virtually not with TPbeta, indicating that
      nascent GPCRs can adopt alternative folding pathways. In vitro pull-down assays
      showed that both receptors can interact directly with CCT7 through their third
      intracellular loops and C-termini. We demonstrate that Trp334 in the TPbeta C
      terminus is critical for the CCT7 interaction and plays an important role in
      TPbeta maturation and cell-surface expression. Of note, introducing a tryptophan
      in the corresponding position of the TPalpha isoform confers the CCT7-binding and
      maturation properties of TPbeta. We show that an interaction with a subunit of
      the CCT/TCP-1 ring complex (TRiC) chaperonin complex is involved in regulating
      aggregation of nascent GPCRs and in promoting their proper maturation and
      expression.

PMID- 27708140
TI  - The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding
      protein TIS11b/BRF1.
AB  - TPA-inducible sequence 11b/butyrate response factor 1 (TIS11b/BRF1) belongs to
      the tristetraprolin (TTP) family of zinc-finger proteins, which bind to mRNAs
      containing AU-rich elements in their 3'-untranslated region and target them for
      degradation. Regulation of TTP family function through phosphorylation by p38 MAP
      kinase and Akt/protein kinase B signaling pathways has been extensively studied.
      In contrast, the role of cAMP-dependent protein kinase (PKA) in the control of
      TTP family activity in mRNA decay remains largely unknown. Here we show that PKA
      activation induces TIS11b gene expression and protein phosphorylation. Site
      directed mutagenesis combined with kinase assays and specific phosphosite
      immunodetection identified Ser-54 (S54) and Ser-334 (S334) as PKA target amino
      acids in vitro and in vivo. Phosphomimetic mutation of the C-terminal S334
      markedly increased TIS11b half-life and, unexpectedly, enhanced TIS11b activity
      on mRNA decay. Examination of protein-protein interactions between TIS11b and
      components of the mRNA decay machinery revealed that mimicking phosphorylation at
      S334 enhances TIS11b interaction with the decapping coactivator Dcp1a, while
      preventing phosphorylation at S334 potentiates its interaction with the Ccr4-Not
      deadenylase complex subunit Cnot1. Collectively our findings establish for the
      first time that cAMP-elicited phosphorylation of TIS11b plays a key regulatory
      role in its mRNA decay-promoting function.

PMID- 27708141
TI  - madSTORM: a superresolution technique for large-scale multiplexing at single
      molecule accuracy.
AB  - Investigation of heterogeneous cellular structures using single-molecule
      localization microscopy has been limited by poorly defined localization accuracy
      and inadequate multiplexing capacity. Using fluorescent nanodiamonds as fiducial
      markers, we define and achieve localization precision required for single
      molecule accuracy in dSTORM images. Coupled with this advance, our new
      multiplexing strategy, madSTORM, allows accurate targeting of multiple molecules
      using sequential binding and elution of fluorescent antibodies. madSTORM is used
      on an activated T-cell to localize 25 epitopes, 14 of which are on components of
      the same multimolecular T-cell receptor complex. We obtain an average
      localization precision of 2.6 nm, alignment error of 2.0 nm, and <0.01% cross
      talk. Combining these technical advances affords the ability to move beyond
      obtaining superresolved structures to defining spatial relationships among
      constituent molecules within structures. Probing the molecular topology of
      complex signaling cascades and other heterogeneous networks is feasible with
      madSTORM.

PMID- 27708142
TI  - Commentary: Stent-Graft to Treat Specific Ascending Aorta Pathology: Waiting for
      the Instructions for Use.

PMID- 27708144
TI  - Commentary: Identifying the Best Device for Infrapopliteal Revascularization
      Through Quantitative Evidence Synthesis.

PMID- 27708143
TI  - Comparative Effectiveness of Plain Balloon Angioplasty, Bare Metal Stents, Drug
      Coated Balloons, and Drug-Eluting Stents for the Treatment of Infrapopliteal
      Artery Disease: Systematic Review and Bayesian Network Meta-analysis of
      Randomized Controlled Trials.
AB  - PURPOSE: To report a Bayesian network meta-analysis of randomized controlled
      trials (RCTs) comparing bare metal stents (BMS), paclitaxel-coated balloons
      (PCBs), and drug-eluting stents (DES) with balloon angioplasty (BA) or with each
      other in the infrapopliteal arteries. METHODS: Sixteen RCTs comprising 1805
      patients with 1-year median follow-up were analyzed. Bayesian random effects
      binomial models were employed (WinBUGS). Relative treatment effects were
      expressed as odds ratios (ORs) with 95% credible intervals (CrI), and the
      cumulative rank probabilities were calculated to provide hierarchies of competing
      treatments. Quality of evidence (QoE) was assessed with the GRADE (grading of
      recommendations assessment, development, and evaluation) system. Sensitivity,
      heterogeneity, and consistency analyses were performed. RESULTS: There was high
      QoE that infrapopliteal DES significantly reduced restenosis compared with BMS
      (OR 0.26, 95% CrI 0.12 to 0.51) and BA (OR 0.22, 95% CrI 0.11 to 0.45). Likewise,
      DES significantly reduced target lesion revascularization (TLR) compared with BA
      (OR 0.41, 95% CrI 0.22 to 0.75) and BMS (OR 0.26, 95% CrI 0.15 to 0.45).
      Paclitaxel-coated balloons also reduced TLR compared with BA (OR 0.55, 95% CrI
      0.34 to 0.90) and BMS (OR 0.35, 95% CrI 0.18 to 0.67), but QoE was low to
      moderate. BA had lower TLR than BMS (OR 0.63, 95% CrI 0.40 to 0.99) with high
      QoE. DES was the only treatment that significantly reduced limb amputations
      compared with BA (OR 0.58, 95% CrI 0.35 to 0.96), PCB (OR 0.51, 95% CrI 0.26 to
      0.98), or BMS (OR 0.38, 95% CrI 0.19 to 0.72) with moderate to high QoE. DES also
      significantly improved wound healing compared with BA (OR 2.02, 95% CrI 1.01 to
      4.07) or BMS (OR 3.45, 95% CrI 1.41 to 8.73) with high QoE. Results were stable
      on sensitivity and meta-regression analyses without any significant publication
      bias or inconsistency. CONCLUSION: Infrapopliteal DES were associated with
      significantly lower rates of restenosis, TLR, and amputations and improved wound
      healing compared to BA and BMS. DES also significantly reduced amputations
      compared with PCB.

PMID- 27708146
TI  - Migratory life histories explain the extreme egg-size dimorphism of Eudyptes
      penguins.
AB  - When successive stages in the life history of an animal directly overlap,
      physiological conflicts can arise resulting in carryover effects from one stage
      to another. The extreme egg-size dimorphism (ESD) of Eudyptes penguins, where the
      first-laid A-egg is approximately 18-57% smaller than the second-laid B-egg, has
      interested researchers for decades. Recent studies have linked variation in this
      trait to a carryover effect of migration that limits the physiology of yolk
      production and egg sizes. We assembled data on ESD and estimates of migration
      reproduction overlap in penguin species and use phylogenetic methods to test the
      idea that migration-reproduction overlap explains variation in ESD. We show that
      migration overlap is generally restricted to Eudyptes relative to non-Eudyptes
      penguins, and that this overlap (defined as the amount of time that egg
      production occurs on land versus at sea during homeward migration) is
      significantly and positively correlated with the degree of ESD in Eudyptes In the
      non-Eudyptes species, however, ESD was unrelated to migration overlap as these
      species mostly produce their clutches on land. Our results support the recent
      hypothesis that extreme ESD of Eudyptes penguins evolved, in part, as a response
      to selection for a pelagic overwinter migration behaviour. This resulted in a
      temporal overlap with, and thus a constraint on, the physiology of follicle
      development, leading to smaller A-egg size and greater ESD.

PMID- 27708145
TI  - Capuchins, space, time and memory: an experimental test of what-where-when memory
      in wild monkeys.
AB  - There is considerable controversy about the existence, extent and adaptive value
      of integrated multimodal memory in non-human animals. Building on prior results
      showing that wild capuchin monkeys in Argentina appear to recall both the
      location and amount of food at patches they had previously visited, I tested
      whether they also track and use elapsed time as a basis for decisions about which
      feeding patches to visit. I presented them with an experimental array of eight
      feeding sites, at each of which food rewards increased with increasing elapsed
      time since the previous visit, similar to the pattern of ripe fruit accumulation
      in natural feeding trees. Over the course of 68 days, comprising two distinct
      renewal rate treatments, one group repeatedly visited sites in the feeding array,
      generating 212 valid choices between sites. Comparison of observations against
      simulated movements and multinomial statistical models shows that the monkeys'
      choices were most consistent with dynamic memory for elapsed time specific to
      each of the eight sites. Thus, it appears that capuchin monkeys possess and use
      integrated memories of prior food patch use, including where the patch is
      relative to their current location, how productive the patch is and how long it
      has been since they last visited the patch. Natural selection to use such
      integrated memories in foraging tasks may provide an ecologically relevant basis
      for the evolution of complex intelligence in primates.

PMID- 27708147
TI  - Evolution of bacterial recombinase A (recA) in eukaryotes explained by addition
      of genomic data of key microbial lineages.
AB  - Recombinase enzymes promote DNA repair by homologous recombination. The genes
      that encode them are ancestral to life, occurring in all known dominions:
      viruses, Eubacteria, Archaea and Eukaryota. Bacterial recombinases are also
      present in viruses and eukaryotic groups (supergroups), presumably via ancestral
      events of lateral gene transfer. The eukaryotic recA genes have two distinct
      origins (mitochondrial and plastidial), whose acquisition by eukaryotes was
      possible via primary (bacteria-eukaryote) and/or secondary (eukaryote-eukaryote)
      endosymbiotic gene transfers (EGTs). Here we present a comprehensive phylogenetic
      analysis of the recA genealogy, with substantially increased taxonomic sampling
      in the bacteria, viruses, eukaryotes and a special focus on the key eukaryotic
      supergroup Amoebozoa, earlier represented only by Dictyostelium We demonstrate
      that several major eukaryotic lineages have lost the bacterial recombinases
      (including Opisthokonta and Excavata), whereas others have retained them
      (Amoebozoa, Archaeplastida and the SAR-supergroups). When absent, the bacterial
      recA homologues may have been lost entirely (secondary loss of canonical
      mitochondria) or replaced by other eukaryotic recombinases. RecA proteins have a
      transit peptide for organellar import, where they act. The reconstruction of the
      RecA phylogeny with its EGT events presented here retells the intertwined
      evolutionary history of eukaryotes and bacteria, while further illuminating the
      events of endosymbiosis in eukaryotes by expanding the collection of widespread
      genes that provide insight to this deep history.

PMID- 27708148
TI  - Genetic basis of priority effects: insights from nectar yeast.
AB  - Priority effects, in which the order of species arrival dictates community
      assembly, can have a major influence on species diversity, but the genetic basis
      of priority effects remains unknown. Here, we suggest that nitrogen scavenging
      genes previously considered responsible for starvation avoidance may drive
      priority effects by causing rapid resource depletion. Using single-molecule
      sequencing, we de novo assembled the genome of the nectar-colonizing yeast,
      Metschnikowia reukaufii, across eight scaffolds and complete mitochondrion, with
      gap-free coverage over gene spaces. We found a high rate of tandem gene
      duplication in this genome, enriched for nitrogen metabolism and transport. Both
      high-capacity amino acid importers, GAP1 and PUT4, present as tandem gene arrays,
      were highly expressed in synthetic nectar and regulated by the availability and
      quality of amino acids. In experiments with competitive nectar yeast, Candida
      rancensis, amino acid addition alleviated suppression of C. rancensis by early
      arrival of M. reukaufii, corroborating that amino acid scavenging may contribute
      to priority effects. Because niche pre-emption via rapid resource depletion may
      underlie priority effects in a broad range of microbial, plant and animal
      communities, nutrient scavenging genes like the ones we considered here may be
      broadly relevant to understanding priority effects.

PMID- 27708149
TI  - Urban warming reduces aboveground carbon storage.
AB  - A substantial amount of global carbon is stored in mature trees. However, no
      experiments to date test how warming affects mature tree carbon storage. Using a
      unique, citywide, factorial experiment, we investigated how warming and insect
      herbivory affected physiological function and carbon sequestration (carbon stored
      per year) of mature trees. Urban warming increased herbivorous arthropod
      abundance on trees, but these herbivores had negligible effects on tree carbon
      sequestration. Instead, urban warming was associated with an estimated 12% loss
      of carbon sequestration, in part because photosynthesis was reduced at hotter
      sites. Ecosystem service assessments that do not consider urban conditions may
      overestimate urban tree carbon storage. Because urban and global warming are
      becoming more intense, our results suggest that urban trees will sequester even
      less carbon in the future.

PMID- 27708150
TI  - Temporal patterns of local adaptation in soil pseudomonads.
AB  - Strong divergent selection leading to local adaptation is often invoked to
      explain the staggering diversity of bacteria in microbial ecosystems. However,
      examples of specialization by bacterial clones to alternative niches in nature
      are rare. Here, we investigate the extent of local adaptation in natural isolates
      of pseudomonads and their relatives to their soil environments across both space
      and time. Though most isolates grew well in most environments, patchily
      distributed low-quality environments were found to drive specialization. In
      contrast to experimental evolution work on microbial adaptation, temporal
      adaptation was stronger than spatial adaptation among the isolates and
      environments we sampled. Time-shift analysis of fitness across two seasons of
      growth revealed an unexpectedly strong effect of preadaptation. This pattern of
      apparent future adaptation may be caused by unknown abiotic properties of these
      environments, phages, bacterial competitors or general mechanisms of ecological
      niche release, and warrants future study.

PMID- 27708152
TI  - Pyrodiversity promotes avian diversity over the decade following forest fire.
AB  - An emerging hypothesis in fire ecology is that pyrodiversity increases species
      diversity. We test whether pyrodiversity-defined as the standard deviation of
      fire severity-increases avian biodiversity at two spatial scales, and whether and
      how this relationship may change in the decade following fire. We use a dynamic
      Bayesian community model applied to a multi-year dataset of bird surveys at 1106
      points sampled across 97 fires in montane California. Our results provide strong
      support for a positive relationship between pyrodiversity and bird diversity.
      This relationship interacts with time since fire, with pyrodiversity having a
      greater effect on biodiversity at 10 years post-fire than at 1 year post-fire.
      Immediately after fires, patches of differing burn severities hold similar bird
      communities, but over the ensuing decade, bird assemblages within patches of
      contrasting severities differentiate. When evaluated at the scale of individual
      fires, fires with a greater heterogeneity of burn severities hold substantially
      more species. High spatial heterogeneity in severity, sometimes called 'mixed
      severity fire', is a natural part of wildfire regimes in western North America,
      but may be jeopardized by climate change and a legacy of fire suppression. Forest
      management that encourages mixed-severity fire may be critical for sustaining
      biodiversity across fire-prone landscapes.

PMID- 27708151
TI  - Blastoderm segmentation in Oncopeltus fasciatus and the evolution of insect
      segmentation mechanisms.
AB  - Segments are formed simultaneously in the blastoderm of the fly Drosophila
      melanogaster through a hierarchical cascade of interacting transcription factors.
      Conversely, in many insects and in all non-insect arthropods most segments are
      formed sequentially from the posterior. We have looked at segmentation in the
      milkweed bug Oncopeltus fasciatus. Posterior segments are formed sequentially,
      through what is probably the ancestral arthropod mechanism. Formation of anterior
      segments bears many similarities to the Drosophila segmentation mode. These
      segments appear nearly simultaneously in the blastoderm, via a segmentation
      cascade that involves orthologues of Drosophila gap genes working through a
      functionally similar mechanism. We suggest that simultaneous blastoderm
      segmentation evolved at or close to the origin of holometabolous insects, and
      formed the basis for the evolution of the segmentation mode seen in Drosophila We
      discuss the changes in segmentation mechanisms throughout insect evolution, and
      suggest that the appearance of simultaneous segmentation as a novel feature of
      holometabolous insects may have contributed to the phenomenal success of this
      group.

PMID- 27708153
TI  - Density-dependent changes in effective area occupied for sea-bottom-associated
      marine fishes.
AB  - The spatial distribution of marine fishes can change for many reasons, including
      density-dependent distributional shifts. Previous studies show mixed support for
      either the proportional-density model (PDM; no relationship between abundance and
      area occupied, supported by ideal-free distribution theory) or the basin model
      (BM; positive abundance-area relationship, supported by density-dependent habitat
      selection theory). The BM implies that fishes move towards preferred habitat as
      the population declines. We estimate the average relationship using bottom trawl
      data for 92 fish species from six marine regions, to determine whether the BM or
      PDM provides a better description for sea-bottom-associated fishes. We fit a
      spatio-temporal model and estimate changes in effective area occupied and
      abundance, and combine results to estimate the average abundance-area
      relationship as well as variability among taxa and regions. The average
      relationship is weak but significant (0.6% increase in area for a 10% increase in
      abundance), whereas only a small proportion of species-region combinations show a
      negative relationship (i.e. shrinking area when abundance increases).
      Approximately one-third of combinations (34.6%) are predicted to increase in area
      more than 1% for every 10% increase in abundance. We therefore infer that
      population density generally changes faster than effective area occupied during
      abundance changes. Gadiformes have the strongest estimated relationship (average
      1.0% area increase for every 10% abundance increase) followed by
      Pleuronectiformes and Scorpaeniformes, and the Eastern Bering Sea shows a strong
      relationship between abundance and area occupied relative to other regions. We
      conclude that the BM explains a small but important portion of spatial dynamics
      for sea-bottom-associated fishes, and that many individual populations merit
      cautious management during population declines, because a compressed range may
      increase the efficiency of harvest.

PMID- 27708154
TI  - Dynamic sinking behaviour in marine phytoplankton: rapid changes in buoyancy may
      aid in nutrient uptake.
AB  - Phytoplankton sinking is an important property that can determine community
      composition in the photic zone and material loss to the deep ocean. To date,
      studies of diatom suspension have relied on bulk measurements with assumptions
      that bulk rates adequately capture the essential characteristics of diatom
      sinking. However, recent work has illustrated that individual diatom sinking
      rates vary considerably from the mean bulk rate. In this study, we apply high
      resolution optical techniques, individual-based observations of diatom sinking
      and a recently developed method of flow visualization around freely sinking
      cells. The results show that in both field samples and laboratory cultures, some
      large species of centric diatoms are capable of a novel behaviour, whereby cells
      undergo bursts of rapid sinking that alternate with near-zero sinking rates on
      the timescales of seconds. We also demonstrate that this behaviour is under
      direct metabolic control of the cell. We discuss these results in the context of
      implications for nutrient flux to the cell surface. While nutrient flux in large
      diatoms increases during fast sinking, current mass transport models cannot
      incorporate the unsteady sinking behaviour observed in this study. However, large
      diatoms appear capable of benefiting from the enhanced nutrient flux to their
      surface during rapid sinking even during brief intervening periods of near-zero
      sinking rates.

PMID- 27708156
TI  - Correction to 'Different effects of invader-native phylogenetic relatedness on
      invasion success and impact: a meta-analysis of Darwin's naturalization
      hypothesis'.

PMID- 27708155
TI  - Strong influence of palaeoclimate on the structure of modern African mammal
      communities.
AB  - Ecological research often assumes that species are adapted to their current
      climatic environments. However, climate fluctuations over geologic timescales
      have influenced species dispersal and extinction, which in turn may affect
      community structure. Modern community structure is likely to be the product of
      both palaeoclimate and modern climate, with the relative degrees of influence of
      past and present climates unknown. Here, we assessed the influence of climate at
      different time periods on the phylogenetic and functional trait structure of 203
      African mammal communities. We found that the climate of the mid-Holocene
      (approx. 6000 years ago) and Last Glacial Maximum (approx. 22 000 years ago) were
      frequently better predictors of community structure than modern climate for
      mammals overall, carnivorans and ungulates. Primate communities were more
      strongly influenced by modern climate than palaeoclimate. Overall, community
      structure of African mammals appears to be related to the ecological flexibility
      of the groups considered here and the regions of continental Africa that they
      occupy. Our results indicate that the future redistribution, expansion and
      contraction of particular biomes due to human activity, such as climate and land
      use change, will differentially affect mammal groups that vary in their
      sensitivity to environmental change.

PMID- 27708157
TI  - Amyloid-beta effects on synapses and memory require AMPA receptor subunit GluA3.
AB  - Amyloid-beta (Abeta) is a prime suspect for causing cognitive deficits during the
      early phases of Alzheimer's disease (AD). Experiments in AD mouse models have
      shown that soluble oligomeric clusters of Abeta degrade synapses and impair
      memory formation. We show that all Abeta-driven effects measured in these mice
      depend on AMPA receptor (AMPAR) subunit GluA3. Hippocampal neurons that lack
      GluA3 were resistant against Abeta-mediated synaptic depression and spine loss.
      In addition, Abeta oligomers blocked long-term synaptic potentiation only in
      neurons that expressed GluA3. Furthermore, although Abeta-overproducing mice
      showed significant memory impairment, memories in GluA3-deficient congenics
      remained unaffected. These experiments indicate that the presence of GluA3
      containing AMPARs is critical for Abeta-mediated synaptic and cognitive deficits.

PMID- 27708158
TI  - One-dimensional nanowires of pseudoboehmite (aluminum oxyhydroxide gamma-AlOOH).
AB  - We report the discovery of a 1D crystalline structure of aluminum oxyhydroxide.
      It was found in a commercial product of fibrous pseudoboehmite (PB), gamma-AlOOH,
      synthesized easily with low cost. The thinnest fiber found was a ribbon-like
      structure of only two layers of an Al-O octahedral double sheet having a
      submicrometer length along its c axis and 0.68-nm thickness along its b axis.
      This thickness is only slightly larger than half of the lattice parameter of the
      b-axis unit cell of the boehmite crystal (b/2 = 0.61 nm). Moreover, interlayer
      splittings having an average width of 1 nm inside the fibrous PB are found. These
      wider interlayer spaces may have intercalation of water, which is suggested by
      density functional theory (DFT) calculation. The fibers appear to grow as almost
      isolated individual filaments in aqueous Al-hydroxide sols and the growth
      direction of fibrous PB is always along its c axis.

PMID- 27708159
TI  - Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2
      deficiency in mice.
AB  - We describe a metabolic disorder characterized by lipodystrophy, hepatic
      steatosis, insulin resistance, severe diabetes, and growth retardation observed
      in mice carrying N-ethyl-N-nitrosourea (ENU)-induced mutations. The disorder was
      ascribed to a mutation of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2)
      and was mimicked by a CRISPR/Cas9-targeted null allele of the same gene. Kbtbd2
      encodes a BTB-Kelch family substrate recognition subunit of the Cullin-3-based E3
      ubiquitin ligase. KBTBD2 targeted p85alpha, the regulatory subunit of the
      phosphoinositol-3-kinase (PI3K) heterodimer, causing p85alpha ubiquitination and
      proteasome-mediated degradation. In the absence of KBTBD2, p85alpha accumulated
      to 30-fold greater levels than in wild-type adipocytes, and excessive p110-free
      p85alpha blocked the binding of p85alpha-p110 heterodimers to IRS1, interrupting
      the insulin signal. Both transplantation of wild-type adipose tissue and
      homozygous germ line inactivation of the p85alpha-encoding gene Pik3r1 rescued
      diabetes and hepatic steatosis phenotypes of Kbtbd2-/- mice. Kbtbd2 was down
      regulated in diet-induced obese insulin-resistant mice in a leptin-dependent
      manner. KBTBD2 is an essential regulator of the insulin-signaling pathway,
      modulating insulin sensitivity by limiting p85alpha abundance.

PMID- 27708160
TI  - Environmental and genetic factors support the dissociation between alpha
      synuclein aggregation and toxicity.
AB  - Synucleinopathies are a group of progressive disorders characterized by the
      abnormal aggregation and accumulation of alpha-synuclein (aSyn), an abundant
      neuronal protein that can adopt different conformations and biological
      properties. Recently, aSyn pathology was shown to spread between neurons in a
      prion-like manner. Proteins like aSyn that exhibit self-propagating capacity
      appear to be able to adopt different stable conformational states, known as
      protein strains, which can be modulated both by environmental and by protein
      intrinsic factors. Here, we analyzed these factors and found that the unique
      combination of the neurodegeneration-related metal copper and the pathological
      H50Q aSyn mutation induces a significant alteration in the aggregation properties
      of aSyn. We compared the aggregation of WT and H50Q aSyn with and without copper,
      and assessed the effects of the resultant protein species when applied to primary
      neuronal cultures. The presence of copper induces the formation of structurally
      different and less-damaging aSyn aggregates. Interestingly, these aggregates
      exhibit a stronger capacity to induce aSyn inclusion formation in recipient
      cells, which demonstrates that the structural features of aSyn species determine
      their effect in neuronal cells and supports a lack of correlation between
      toxicity and inclusion formation. In total, our study provides strong support in
      favor of the hypothesis that protein aggregation is not a primary cause of
      cytotoxicity.

PMID- 27708163
TI  - Scale-free channeling patterns near the onset of erosion of sheared granular
      beds.
AB  - Erosion shapes our landscape and occurs when a sufficient shear stress is exerted
      by a fluid on a sedimented layer. What controls erosion at a microscopic level
      remains debated, especially near the threshold forcing where it stops. Here we
      study, experimentally, the collective dynamics of the moving particles, using a
      setup where the system spontaneously evolves toward the erosion onset. We find
      that the spatial organization of the erosion flux is heterogeneous in space and
      occurs along channels of local flux sigma whose distribution displays scaling
      near threshold and follows [Formula: see text], where J is the mean erosion flux.
      Channels are strongly correlated in the direction of forcing but not in the
      transverse direction. We show that these results quantitatively agree with a
      model where the dynamics is governed by the competition of disorder (which
      channels mobile particles) and particle interactions (which reduces channeling).
      These observations support that, for laminar flows, erosion is a dynamical phase
      transition that shares similarity with the plastic depinning transition occurring
      in dirty superconductors. The methodology we introduce here could be applied to
      probe these systems as well.

PMID- 27708162
TI  - The Architecture of Trypanosoma brucei editosomes.
AB  - Uridine insertion and deletion RNA editing generates functional mitochondrial
      mRNAs in Trypanosoma brucei Editing is catalyzed by three distinct ~20S
      editosomes that have a common set of 12 proteins, but are typified by mutually
      exclusive RNase III endonucleases with distinct cleavage specificities and unique
      partner proteins. Previous studies identified a network of protein-protein
      interactions among a subset of common editosome proteins, but interactions among
      the endonucleases and their partner proteins, and their interactions with common
      subunits were not identified. Here, chemical cross-linking and mass spectrometry,
      comparative structural modeling, and genetic and biochemical analyses were used
      to define the molecular architecture and subunit organization of purified
      editosomes. We identified intra- and interprotein cross-links for all editosome
      subunits that are fully consistent with editosome protein structures and
      previously identified interactions, which we validated by genetic and biochemical
      studies. The results were used to create a highly detailed map of editosome
      protein domain proximities, leading to identification of molecular interactions
      between subunits, insights into the functions of noncatalytic editosome proteins,
      and a global understanding of editosome architecture.

PMID- 27708161
TI  - Arabidopsis small nucleolar RNA monitors the efficient pre-rRNA processing during
      ribosome biogenesis.
AB  - Ribosome production in eukaryotes requires the complex and precise coordination
      of several hundred assembly factors, including many small nucleolar RNAs
      (snoRNAs). However, at present, the distinct role of key snoRNAs in ribosome
      biogenesis remains poorly understood in higher plants. Here we report that a
      previously uncharacterized C (RUGAUGA)/D (CUGA) type snoRNA, HIDDEN TREASURE 2
      (HID2), acts as an important regulator of ribosome biogenesis through a snoRNA
      rRNA interaction. Nucleolus-localized HID2 is actively expressed in Arabidopsis
      proliferative tissues, whereas defects in HID2 cause a series of developmental
      defects reminiscent of ribosomal protein mutants. HID2 associates with the
      precursor 45S rRNA and promotes the efficiency and accuracy of pre-rRNA
      processing. Intriguingly, disrupting HID2 in Arabidopsis appears to impair the
      integrity of 27SB, a key pre-rRNA intermediate that generates 25S and 5.8S rRNA
      and is known to be vital for the synthesis of the 60S large ribosomal subunit and
      also produces an imbalanced ribosome profile. Finally, we demonstrate that the
      antisense-box of HID2 is both functionally essential and highly conserved in
      eukaryotes. Overall, our study reveals the vital and possibly conserved role of a
      snoRNA in monitoring the efficiency of pre-rRNA processing during ribosome
      biogenesis.

PMID- 27708164
TI  - Superantigens hyperinduce inflammatory cytokines by enhancing the B7-2/CD28
      costimulatory receptor interaction.
AB  - Full T-cell activation requires interaction between the costimulatory receptors
      B7-2 and CD28. By binding CD28, bacterial superantigens elicit harmful
      inflammatory cytokine overexpression through an unknown mechanism. We show that,
      by engaging not only CD28 but also its coligand B7-2 directly, superantigens
      potently enhance the avidity between B7-2 and CD28, inducing thereby T-cell
      hyperactivation. Using the same 12-aa beta-strand-hinge-alpha-helix domain,
      superantigens engage both B7-2 and CD28 at their homodimer interfaces, areas
      remote from where these coreceptors interact, implying that inflammatory
      signaling can be controlled through the receptor homodimer interfaces. Short B7-2
      dimer interface mimetic peptides bind diverse superantigens, prevent superantigen
      binding to cell-surface B7-2 or CD28, attenuate inflammatory cytokine
      overexpression, and protect mice from lethal superantigen challenge. Thus,
      superantigens induce a cytokine storm not only by mediating the interaction
      between MHC-II molecule and T-cell receptor but also, critically, by promoting B7
      2/CD28 coreceptor engagement, forcing the principal costimulatory axis to signal
      excessively. Our results reveal a role for B7-2 as obligatory receptor for
      superantigens. B7-2 homodimer interface mimotopes prevent superantigen lethality
      by blocking the superantigen-host costimulatory receptor interaction.

PMID- 27708165
TI  - Accumulation of specific sterol precursors targets a MAP kinase cascade mediating
      cell-cell recognition and fusion.
AB  - Sterols are vital components of eukaryotic cell membranes. Defects in sterol
      biosynthesis, which result in the accumulation of precursor molecules, are
      commonly associated with cellular disorders and disease. However, the effects of
      these sterol precursors on the metabolism, signaling, and behavior of cells are
      only poorly understood. In this study, we show that the accumulation of only
      ergosterol precursors with a conjugated double bond in their aliphatic side chain
      specifically disrupts cell-cell communication and fusion in the fungus Neurospora
      crassa Genetically identical germinating spores of this fungus undergo cell-cell
      fusion, thereby forming a highly interconnected supracellular network during
      colony initiation. Before fusion, the cells use an unusual signaling mechanism
      that involves the coordinated and alternating switching between signal sending
      and receiving states of the two fusion partners. Accumulation of only ergosterol
      precursors with a conjugated double bond in their aliphatic side chain disrupts
      this coordinated cell-cell communication and suppresses cell fusion. These
      specific sterol precursors target a single ERK-like mitogen-activated protein
      (MAP) kinase (MAK-1)-signaling cascade, whereas a second MAP kinase pathway (MAK
      2), which is also involved in cell fusion, is unaffected. These observations
      indicate that a minor specific change in sterol structure can exert a strong
      detrimental effect on a key signaling pathway of the cell, resulting in the
      absence of cell fusion.

PMID- 27708168
TI  - DNA Methylation of the hTERT Gene in Breast Cancer Revisited: Diagnostic and
      Clinical Implications.
AB  - BACKGROUND: It is documented that in tumor cell lines, the hTERT gene exhibits
      prominent methylation at a CpG island rich region about -600 bp upstream of the
      transcription start site, but mixed or allelically absent around +/-150 bp
      region. Given the potential clinical implications of the findings in breast
      cancer diagnostics, we set out to investigate if such findings are reproducible
      on primary surgically resected invasive breast carcinomas. METHODS: The cohort
      consisted of 50 cases of freshly sampled and formalin-fixed paraffin embedded
      (FFPE) invasive breast cancers and normal tissue. A modified quasi-quantitative
      methylation specific polymerase chain reaction was used to determine methylation
      status in cancer relative to normal tissue at the 2 CpG island-rich regions.
      RESULTS: A global hypermethylation is evident at the -600 bp region in both fresh
      and parallel FFPE breast cancers as compared to normal tissue. In contrast, most
      of the tumor and normal tissue remains unmethylated around the +/-150 bp region.
      CONCLUSIONS: Our results support further development of hTERT hypermethylation in
      the -600 bp region as a biomarker for breast cancer diagnostics. The unmethylated
      status of +/-150 bp region in normal breast tissue does not support the
      suggestion that unmethylation is required for hTERT gene expression.

PMID- 27708169
TI  - The Need for Education in Molecular Immunohematology: A Survey of Specialists in
      Blood Banking.
AB  - BACKGROUND: Within transfusion medicine, the education of molecular technologies
      lacks standardization. OBJECTIVE: To address this problem, we surveyed specialist
      in blood bank technology (SBBT) programs, immunohematology reference
      laboratories, and SBBT graduates to define its current state. METHODS: An
      anonymous online survey (SurveyMonkey) was emailed to the 15 American Association
      of Blood Banks (AABB) SBBT programs, 59 AABB IRLs, and 82 SBBT graduates.
      RESULTS: In the didactic portion of the SBBT curriculum, all programs incorporate
      knowledge base of blood groups, 13 incorporate molecular techniques, and 5
      include case studies. Thirteen programs have intentions of expanding the
      knowledge base in molecular topics. Most IRLs (97%) think SBBT programs should
      continue to expand molecular knowledge base. Most graduates (94%) believe more
      molecular topics should be included in the SBBT curriculum; however, only 50%
      believe they currently apply their molecular knowledge in their post-graduate
      employment. CONCLUSION: We propose a more descriptive molecular diagnostics
      curriculum for SBBT programs to help standardize the education of molecular
      topics.

PMID- 27708166
TI  - Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer
      research.
AB  - Current mouse models for colorectal cancer often differ significantly from human
      colon cancer, being largely restricted to the small intestine. Here, we aim to
      develop a colon-specific inducible mouse model that can faithfully recapitulate
      human colon cancer initiation and progression. Carbonic anhydrase I (Car1) is a
      gene expressed uniquely in colonic epithelial cells. We generated a colon
      specific inducible Car1CreER knock-in (KI) mouse with broad Cre activity in
      epithelial cells of the proximal colon and cecum. Deletion of the tumor
      suppressor gene Apc using the Car1CreER KI caused tumor formation in the cecum
      but did not yield adenomas in the proximal colon. Mutation of both Apc and Kras
      yielded microadenomas in both the cecum and the proximal colon, which progressed
      to macroadenomas with significant morbidity. Aggressive carcinomas with some
      invasion into lymph nodes developed upon combined induction of oncogenic
      mutations of Apc, Kras, p53, and Smad4 Importantly, no adenomas were observed in
      the small intestine. Additionally, we observed tumors from differentiated Car1
      expressing cells with Apc/Kras mutations, suggesting that a top-down model of
      intestinal tumorigenesis can occur with multiple mutations. Our results establish
      the Car1CreER KI as a valuable mouse model to study colon-specific tumorigenesis
      and metastasis as well as cancer-cell-of-origin questions.

PMID- 27708171
TI  - Erratum.

PMID- 27708170
TI  - Prevalence and Clinical Utility of "Incidental" Critical Values Resulting From
      Critical Care Laboratory Testing.
AB  - OBJECTIVE: Panels of clinical laboratory testing may generate "incidental"
      critical values from unordered parameters. Existing regulations do not clearly
      delineate guidelines for handling incidental critical values. The objective of
      this study was to examine the patterns and clinical utility of incidental
      critical values at 2 critical care laboratories within an academic medical
      center. METHODS: In this retrospective study, the electronic health record and
      laboratory information system were reviewed for incidental critical results
      obtained from blood gas analyzer analysis of whole blood specimens between
      November 2010 and August 2014. RESULTS: Within the retrospective time period,
      9,092 incidental critical results were documented, of which only 11.8% were added
      to the "parent" order following clinical notification. Incidental critical
      results frequently occurred in patients who had recent critical values for the
      same parameter. CONCLUSION: In this study, at an academic medical center,
      incidental critical values associated with blood gas analyzers were added on at a
      low rate and often provided redundant information. Relative to the manual effort
      involved in care providers' notification and documentation of results, incidental
      critical values appear to have low clinical utility.

PMID- 27708167
TI  - Interfibrillar stiffening of echinoderm mutable collagenous tissue demonstrated
      at the nanoscale.
AB  - The mutable collagenous tissue (MCT) of echinoderms (e.g., sea cucumbers and
      starfish) is a remarkable example of a biological material that has the unique
      attribute, among collagenous tissues, of being able to rapidly change its
      stiffness and extensibility under neural control. However, the mechanisms of MCT
      have not been characterized at the nanoscale. Using synchrotron small-angle X-ray
      diffraction to probe time-dependent changes in fibrillar structure during in situ
      tensile testing of sea cucumber dermis, we investigate the ultrastructural
      mechanics of MCT by measuring fibril strain at different chemically induced
      mechanical states. By measuring a variable interfibrillar stiffness (EIF), the
      mechanism of mutability at the nanoscale can be demonstrated directly. A model of
      stiffness modulation via enhanced fibrillar recruitment is developed to explain
      the biophysical mechanisms of MCT. Understanding the mechanisms of MCT
      quantitatively may have applications in development of new types of mechanically
      tunable biomaterials.

PMID- 27708172
TI  - Handling Big Data in Modern Healthcare.
AB  - The constant growth of medical knowledge and the increases in specialization in
      clinical practice have created a significant need to share and access patient
      information with speed and efficiency. However, current technology is centered on
      processing data, rather than gathering information. To realize the potential of
      modern technology in improving patient health, merely collecting and storing data
      are insufficient: one must convert these data into information and knowledge. In
      this article, I present an overview of 2 recent advances in technology and their
      assimilation into the practice of medicine, in the attempt to make clinical data
      meaningful and then to learn from aggregated clinical data. We address the
      emergence of clinical data warehouses (CDWs) and health information exchanges
      (HIEs), as features of the Health Information Technology for Economic and
      Clinical Health (HITECH) Act. This act, enacted in the United States as part of
      the American Recovery and Reinvestment Act of 2009, was signed into law on
      February 17, 2009, to promote the adoption and meaningful use of health
      information technology.

PMID- 27708176
TI  - About the Journal.

PMID- 27708173
TI  - IQCP: Guideline and Helpful Tools for Implementation.
AB  - This article will help laboratories understand what changed with external quality
      control testing, why it changed, who changed it, when the changes became
      effective, and how these changes affect clinical laboratories. The new
      Individualized Quality Control Plan (IQCP) option that became effective January
      1, 2016, will be explained. Three other quality control changes that took effect
      January 1, 2016, and dramatically affect quality control requirements for
      antimicrobial susceptibility testing, identification test systems, and exempt
      culture media will also be explained. Guidelines and tools are provided that can
      assist laboratories in determining what is eligible for IQCP and how to design an
      IQCP program.

PMID- 27708177
TI  - Neurophysiological Intraoperative Monitoring During Aortic Arch Surgery.
AB  - Circulatory management during replacement of the aortic arch is complex and
      involves a period of circulatory arrest to provide a bloodless field during arch
      vessel anastomosis. To guard against ischemic brain injury, tissue metabolic
      demand is reduced by systemically cooling the patient prior to circulatory
      arrest. Neurophysiological intraoperative monitoring (NIOM) is often used during
      the course of these procedures to provide contemporaneous assessment of brain
      status to help direct circulatory management decisions and detect brain ischemia.
      In this review, we discuss the characteristics of electrocerebral activity
      through the process of cooling, circulatory arrest, and rewarming as depicted
      through commonly used NIOM modalities, including electroencephalography and
      peripheral nerve somatosensory-evoked potentials. Attention is directed toward
      the role NIOM has traditionally played during deep hypothermic circulatory
      arrest, where it is used to define the point of electrocerebral inactivity or
      maximal cerebral metabolic suppression prior to initiating circulatory arrest
      while also discussing the evolving utility of NIOM when systemic circulatory
      arrest is initiated at more moderate degrees of hypothermia in conjunction with
      regional brain perfusion. The use of cerebral tissue oximetry by near-infrared
      spectroscopy as an alternative NIOM modality during surgery of the aortic arch is
      addressed as well. Finally, special considerations for NIOM and the detection of
      spinal cord ischemia during hybrid aortic arch repair and emerging operative
      techniques are also discussed.

PMID- 27708178
TI  - Pattern Recognition-Assisted Infrared Library Searching of the Paint Data Query
      Database to Enhance Lead Information from Automotive Paint Trace Evidence.
AB  - Multilayered automotive paint fragments, which are one of the most complex
      materials encountered in the forensic science laboratory, provide crucial links
      in criminal investigations and prosecutions. To determine the origin of these
      paint fragments, forensic automotive paint examiners have turned to the paint
      data query (PDQ) database, which allows the forensic examiner to compare the
      layer sequence and color, texture, and composition of the sample to paint systems
      of the original equipment manufacturer (OEM). However, modern automotive paints
      have a thin color coat and this layer on a microscopic fragment is often too thin
      to obtain accurate chemical and topcoat color information. A search engine has
      been developed for the infrared (IR) spectral libraries of the PDQ database in an
      effort to improve discrimination capability and permit quantification of
      discrimination power for OEM automotive paint comparisons. The similarity of IR
      spectra of the corresponding layers of various records for original finishes in
      the PDQ database often results in poor discrimination using commercial library
      search algorithms. A pattern recognition approach employing pre-filters and a
      cross-correlation library search algorithm that performs both a forward and
      backward search has been used to significantly improve the discrimination of IR
      spectra in the PDQ database and thus improve the accuracy of the search. This
      improvement permits inter-comparison of OEM automotive paint layer systems using
      the IR spectra alone. Such information can serve to quantify the discrimination
      power of the original automotive paint encountered in casework and further
      efforts to succinctly communicate trace evidence to the courts.

PMID- 27708179
TI  - Understanding and Discrimination of Biofilms of Clinically Relevant
      Microorganisms Using Surface-Enhanced Raman Scattering.
AB  - Biofilm formation is a defense mechanism for microorganisms to survive under both
      natural and stress conditions. Clinically relevant microorganisms threaten
      patient health through biofilm formation on medical devices and implants. It is
      very important to identify biofilm formation in order to suppress their
      pathogenic activities in early stages. With the aim for better understanding
      biofilm formation and possibility of detection, in this study, biofilm formation
      of clinically important microorganisms, Pseudomonas aeruginosa, Staphylococcus
      epidermidis, and Candida albicans are monitored with surface-enhanced Raman
      scattering (SERS). The SERS spectra were collected by mapping a dried droplet
      area where a volume of colloidal silver nanoparticle (AgNP) suspension is placed
      on microorganism culture plate. The spectral changes on the SERS spectra with
      increasing incubation time of the model microorganisms from 4 to 120 h are
      monitored. The unique spectra originating from the biofilms of three pathogenic
      microorganisms and the spectral changes as a result of time-dependent
      concentration fluctuations of biomolecular species in their biofilms including
      carbohydrates, lipids, proteins, and genetic materials allow not only
      identification but also discrimination of biofilms using principal component
      analysis.

PMID- 27708180
TI  - Mid-Esophagus Columnar Metaplasia: What Is the Biopathogenic Pathway?
AB  - We report a case of metaplastic columnar epithelium in the mid-esophagus in a
      patient with history of caustic ingestion. A cardiac-type gastric phenotype, with
      early signs of intestinalization, was confirmed by immunohistochemistry studies
      (MUC5AC, MUC6, SOX2, and CDX2). Nonmetaplastic mucosa had histologic evidence of
      gastroesophageal reflux. In this case, esophageal reepithelization seems to have
      been modulated by acidic gastroesophageal reflux, which might activate
      transcription factors leading to phenotypic reprogramming of the regenerative
      epithelium. Most interestingly, it is a clinical example showcasing the origin of
      columnar metaplasia from stem cells located within the esophageal epithelium.

PMID- 27708181
TI  - A Never Ending Journey: Ectopic Thyroid.

PMID- 27708183
TI  - Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline.
AB  - BACKGROUND: There are few studies of the association between the use of
      antioxidant vitamin supplements and the risk of Alzheimer's disease (AD).
      Cognitive decline is generally viewed as part of the continuum between normal
      aging and AD. OBJECTIVE: To evaluate whether the use of vitamin E and C
      supplements is associated with reduced risks of cognitive impairment, not
      dementia (CIND), AD, or all-cause dementia in a representative sample of older
      persons >=65 years old. METHODS: Data from the Canadian Study of Health and Aging
      (1991-2002), a cohort study of dementia including 3 evaluation waves at 5-yearly
      intervals, were used. Exposure to vitamins E and C was self-reported at baseline
      in a risk factor questionnaire and/or in a clinical examination. RESULTS: The
      data set included 5269 individuals. Compared with those not taking vitamin
      supplements, the age-, sex-, and education-adjusted hazard ratios of CIND, AD,
      and all-cause dementia were, respectively, 0.77 (95% CI = 0.60-0.98), 0.60 (95%
      CI = 0.42-0.86), and 0.62 (95% CI = 0.46-0.83) for those taking vitamin E and/or
      C supplements. Results remained significant in fully adjusted models except for
      CIND. Similar results were observed when vitamins were analyzed separately.
      CONCLUSIONS: This analysis suggests that the use of vitamin E and C supplements
      is associated with a reduced risk of cognitive decline. Further investigations
      are needed to determine their value as a primary prevention strategy.

PMID- 27708182
TI  - Microencapsulation of porcine thyroid cell organoids within a polymer
      microcapsule construct.
AB  - Hypothyroidism is a common condition of hormone deficiency, and oral
      administration of thyroid hormones is currently the only available treatment
      option. However, there are some disadvantages with this treatment modality
      including compliance challenges to patients. Therefore, a physiologically based
      alternative therapy for hypothyroidism with little or no side-effects is needed.
      In this study, we have developed a method for microencapsulating porcine thyroid
      cells as a thyroid hormone replacement approach. The hybrid wall of the polymer
      microcapsules permits thyroid hormone release while preventing immunoglobulin
      antibodies from entry. This strategy could potentially enable implantation of the
      microcapsule organoids containing allogeneic or xenogeneic thyroid cells to
      secret hormones over time without the need for immunosuppression of recipients.
      Porcine thyroid cells were isolated and encapsulated in alginate-poly-L-ornithine
      alginate microcapsules using a microfluidic device. The porcine thyroid cells
      formed three-dimensional follicular spheres in the microcapsules with decent cell
      viability and proliferation. Thyroxine release from the encapsulated cells was
      higher than from unencapsulated cells ( P < 0.05) and was maintained during the
      entire duration of experiment (>28 days). These results suggest that the
      microencapsulated thyroid cell organoids may have the potential to be used for
      therapy and/or drug screening.

PMID- 27708184
TI  - Elimination of Plasmodium vivax Malaria in Azerbaijan.
AB  - Azerbaijan in the south caucasus region of far southeastern Europe has a long
      history of malaria endemicity but just successfully eliminated local
      transmission. After a period of relatively stable malaria situation (1960-1970),
      the country witnessed an epidemic followed by a series of outbreaks of various
      magnitudes in the following two decades, all caused by Plasmodium vivax Compared
      with 1993, the number of malaria cases in the country jumped 29 times in 1994,
      123 times in 1995, and 571 times in 1996 at the peak of the epidemic, when 13,135
      cases were officially registered. Incidence rate increased dramatically from
      0.2/100,000 population in 1991 to over 17/100,000 population in 1996. Scaled-up
      malaria control led to the containment of the epidemic and to a dramatic decrease
      of malaria burden nationwide. Azerbaijan has applied contemporary, complex
      control and surveillance strategies and approaches and is currently in the
      prevention of reintroduction phase. This article describes Azerbaijan's public
      health experience in conducting malaria control and elimination interventions
      over several decades until 2013 when the country reached an important milestone
      no indigenous malaria cases were recorded.

PMID- 27708186
TI  - Attacking Plasmodium vivax.
AB  - Discussions beginning in 2012 ultimately led to a landmark document from the
      World Health Organization (WHO) titled, Control and Elimination of Plasmodium
      vivax: A Technical Brief, published in July 2015. That body of work represents
      multiple expert consultations coordinated by the WHO Global Malaria Program,
      along with technical consensus gathering from national malaria control programs
      via the WHO regional offices around the globe. That document thus represents
      thoroughly vetted state-of-the-art recommendations for dealing specifically with
      P. vivax, the first assembly of such by the WHO. This supplement to the journal
      was commissioned by the WHO and compiles the very substantial body of evidence
      and analysis informing those recommendations. This introductory narrative to the
      supplement provides the historical and technological context of global strategy
      for combatting P. vivax and reducing the burdens of morbidity and mortality it
      imposes.

PMID- 27708185
TI  - Epidemiology of Plasmodium vivax in Indonesia.
AB  - Endemic malaria occurs across much of the vast Indonesian archipelago. All five
      species of Plasmodium known to naturally infect humans occur here, along with 20
      species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of
      plasmodia cause the overwhelming majority and virtually equal shares of malaria
      infections in Indonesia: Plasmodium falciparum and Plasmodium vivax The challenge
      posed by P. vivax is especially steep in Indonesia because chloroquine-resistant
      strains predominate, along with Chesson-like strains that relapse quickly and
      multiple times at short intervals in almost all patients. Indonesia's hugely
      diverse human population carries many variants of glucose-6-phosphate
      dehydrogenase (G6PD) deficiency, most of them exhibiting severely impaired enzyme
      activity. Therefore, the patients most likely to benefit from primaquine therapy
      by preventing aggressive relapse, may also be most likely to suffer harm without
      G6PD deficiency screening. Indonesia faces the challenge of controlling and
      eventually eliminating malaria across > 13,500 islands stretching > 5,000 km and
      an enormous diversity of ecological, ethnographic, and socioeconomic settings,
      and extensive human migrations. This article describes the occurrence of P. vivax
      in Indonesia and the obstacles faced in eliminating its transmission.

PMID- 27708187
TI  - Plasmodium vivax Malaria in Cambodia.
AB  - The Cambodian National Strategic Plan for Elimination of Malaria aims to move
      step by step toward elimination of malaria across Cambodia with an initial focus
      on Plasmodium falciparum malaria before achieving elimination of all forms of
      malaria, including Plasmodium vivax in 2025. The emergence of artemisinin
      resistant P. falciparum in western Cambodia over the last decade has drawn global
      attention to support the ultimate goal of P. falciparum elimination, whereas the
      control of P. vivax lags much behind, making the 2025 target gradually less
      achievable unless greater attention is given to P. vivax elimination in the
      country. The following review presents in detail the past and current situation
      regarding P. vivax malaria, activities of the National Malaria Control Program,
      and interventional measures applied. Constraints and obstacles that can
      jeopardize our efforts to eliminate this parasite species are discussed.

PMID- 27708188
TI  - Epidemiology of Plasmodium vivax Malaria in India.
AB  - Historically, malaria in India was predominantly caused by Plasmodium vivax,
      accounting for 53% of the estimated cases. After the spread of drug-resistant
      Plasmodium falciparum in the 1990s, the prevalence of the two species remained
      equivalent at the national level for a decade. By 2014, the proportion of P.
      vivax has decreased to 34% nationally, but with high regional variation. In 2014,
      P. vivax accounted for around 380,000 malaria cases in India; almost a sixth of
      all P. vivax cases reported globally. Plasmodium vivax has remained resistant to
      control measures, particularly in urban areas. Urban malaria is predominantly
      caused by P. vivax and is subject to outbreaks, often associated with increased
      mortality, and triggered by bursts of migration and construction. The
      epidemiology of P. vivax varies substantially within India, including multiple
      relapse phenotypes with varying latencies between primary infection and relapse.
      Moreover, the hypnozoite reservoir maintains transmission potential and enables
      reestablishment of the parasite in areas in which it was thought eradicated. The
      burden of malaria in India is complex because of the highly variable malaria eco
      epidemiological profiles, transmission factors, and the presence of multiple
      Plasmodium species and Anopheles vectors. This review of P. vivax malaria in
      India describes epidemiological trends with particular attention to four states:
      Gujarat, Karnataka, Haryana, and Odisha.

PMID- 27708189
TI  - Epidemiology and Control of Plasmodium vivax in Afghanistan.
AB  - Around half of the population of Afghanistan resides in areas at risk of malaria
      transmission. Two species of malaria (Plasmodium vivax and Plasmodium falciparum)
      account for a high burden of disease-in 2011, there were more than 300,000
      confirmed cases. Around 80-95% of malaria is P. vivax Transmission is seasonal
      and focal, below 2,000 m in altitude, and in irrigated areas which allow breeding
      of anopheline mosquito vectors. Malaria risk is stratified to improve targeting
      of interventions. Sixty-three of 400 districts account for ~85% of cases, and are
      the target of more intense control efforts. Pressure on the disease is maintained
      through case management, surveillance, and use of long-lasting insecticide
      treated nets. Plasmodium vivax treatment is hampered by the inability to safely
      treat latent hypnozoites with primaquine because G6PD deficiency affects up to
      10% of males in some ethnic groups. The risk of vivax malaria recurrence (which
      may be as a result of reinfection or relapse) is around 30-45% in groups not
      treated with primaquine but 3-20% in those given 14-day or 8-week courses of
      primaquine. Greater access to G6PD testing and radical treatment would reduce the
      number of incident cases, reduce the infectious reservoir in the population, and
      has the potential to reduce transmission as a result. Alongside the lack of G6PD
      testing, under-resourcing and poor security hamper the control of malaria. Recent
      gains in reducing the burden of disease are fragile and at risk of reversal if
      pressure on the disease is not maintained.

PMID- 27708192
TI  - Romidepsin-associated cardiac toxicity and ECG changes: A case report and review
      of the literature.
AB  - Background Romidepsin is a novel histone deacetylase inhibitor that is approved
      for the treatment of cutaneous and peripheral T-cell lymphoma in patients who
      have had at least one prior therapy. Romidepsin is generally well tolerated,
      though it comes with a risk of cardiac toxicities. Objective We report a case of
      electrocardiogram changes in a 64-year-old male with enteropathy-associated T
      cell lymphoma, type 2, treated with salvage romidepsin therapy who relapsed after
      non-myeloablative allogeneic sibling peripheral blood stem cell transplant.
      Discussion Although histone deacetylase inhibitors have been investigated for
      many years, they have only recently been translated to clinical use as a therapy
      for malignancies. Furthermore, given their approval for a rare disease,
      clinicians often have limited experience with the dosing and side effects of
      histone deacetylase inhibitors. Conclusion This case report and literature review
      investigates the cardiac side effects of histone deacetylase inhibitors and
      illustrates the importance of cardiac monitoring prior to and during treatment.

PMID- 27708190
TI  - Plasmodium vivax Landscape in Brazil: Scenario and Challenges.
AB  - Brazil is the largest country of Latin America, with a considerable portion of
      its territoritory within the malaria-endemic Amazon region in the North.
      Furthermore, a considerable portion of its territory is located within the Amazon
      region in the north. As a result, Brazil has reported half of the total malaria
      cases in the Americas in the last four decades. Recent progress in malaria
      control has been accompanied by an increasing proportion of Plasmodium vivax,
      underscoring a need for a better understanding of management and control of this
      species and associated challenges. Among these challenges, the contribution of
      vivax malaria relapses, earlier production of gametocytes (compared with
      Plasmodium falciparum), inexistent methods to diagnose hypnozoite carriers, and
      decreasing efficacy of available antimalarials need to be addressed. Innovative
      tools, strategies, and technologies are needed to achieve further progress toward
      sustainable malaria elimination. Further difficulties also arise from dealing
      with the inherent socioeconomic and environmental particularities of the Amazon
      region and its dynamic changes.

PMID- 27708194
TI  - Effects of the Janus Kinase Inhibitor, Tofacitinib, on Testicular Leydig Cell
      Hyperplasia and Adenoma in Rats, and on Prolactin Signaling in Cultured Primary
      Rat Leydig Cells.
AB  - Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of
      rheumatoid arthritis. Tofacitinib preferentially inhibits receptor signaling
      through JAK3 and JAK1, relative to JAK2. In the 2-year rat carcinogenicity study,
      there were tofacitinib, dose-related increases in the incidences of testicular
      Leydig cell hyperplasia and benign adenomas in male rats, and decreased
      incidences of mammary tumors and duct dilatation/galactocele in female rats. Such
      findings in rats are typical of agents, such as dopamine agonists, which decrease
      prolactin (PRL) activity. Since prolactin signals through the JAK2 pathway, we
      hypothesized that these findings were off-target effects due to inhibition of PRL
      signaling via JAK2. The studies reported here were designed to investigate the
      interruption of PRL signaling pathways in Leydig cells. In isolated primary rat
      Leydig cells, PRL increased phosphorylated Signal Transducer and Activator of
      Transcription-5 protein, and mRNA levels for luteinizing hormone receptor.
      Tofacitinib, at concentrations observed in the rat carcinogenicity study, dose
      dependently inhibited these effects. These observations illustrate a novel
      mechanism, the inhibition of prolactin signaling by which modulation of JAK
      activity can modulate PRL signaling pathways to induce Leydig cell tumors in
      rats. Since human Leydig cells lack this PRL dependence for normal function,
      these rodent tumors do not indicate a health risk to human patients.

PMID- 27708193
TI  - Editor's Highlight: Role of Spleen-Derived Macrophages in Ozone-Induced Lung
      Inflammation and Injury.
AB  - Macrophages and inflammatory mediators have been implicated in ozone toxicity. In
      these studies, we used splenectomized (SPX) mice to assess the contribution of
      splenic monocytes to pulmonary inflammation and injury induced by ozone. Cells
      and tissue were collected 24-72 h after exposure of mice to air or ozone (0.8
      ppm, 3 h). Following ozone exposure, increased numbers of pro-inflammatory CD11b
      + Ly6CHi and anti-inflammatory CD11b + Ly6CLo monocytes were observed in spleens
      of control (CTL) mice. CD11b + Ly6CHi and MMP-9+ pro-inflammatory macrophages
      were also observed in lungs of CTL mice after ozone, along with CD11b + Ly6CLo
      and mannose receptor (MR)+ anti-inflammatory macrophages. This was accompanied by
      increased lung expression of proteins involved in monocyte/macrophage trafficking
      including CCL3, CCL4, CCR1, and AT1R. Splenectomy resulted in decreases in pro
      inflammatory macrophages in the lung and down regulation of CCR2, CCL2, and CCL4,
      but increases in CD11b + Ly6CLo anti-inflammatory macrophages. CD11b+Ly6G+Ly6C+
      granulocytic (G)- and monocytic (M)-myeloid derived suppressor cells (MDSC)s were
      also detected in the lungs and spleens of CTL mice; these increased after ozone
      exposure. Splenectomy was associated with a decrease in G-MDSCs in the lung, with
      no effect on M-MDSCs. Changes in lung macrophage subpopulations and MDSCs in SPX
      mice were correlated with reduced ozone toxicity, as measured by decreases in
      bronchoalveolar lavage protein content and reduced 4-hydroxynonenal expression in
      the lung. These data suggest that the spleen is a source of pro
      inflammatory/cytotoxic macrophages that contribute to ozone-induced lung injury,
      inflammation, and oxidative stress.

PMID- 27708191
TI  - Diagnosis and Treatment of Plasmodium vivax Malaria.
AB  - The diagnosis and treatment of Plasmodium vivax malaria differs from that of
      Plasmodium falciparum malaria in fundamentally important ways. This article
      reviews the guiding principles, practices, and evidence underpinning the
      diagnosis and treatment of P. vivax malaria.

PMID- 27708195
TI  - Risk Factors Associated With Inpatient Violence During Medium Security Treatment.
AB  - Violence is a common phenomenon both in regular and forensic psychiatric
      settings, and has a profound impact on staff and other patients. Insight into the
      individual risk factors associated with violence in forensic psychiatric settings
      is rare and is therefore the subject of this research. A retrospective file study
      in three medium security units in Flanders was conducted to compare non-violent
      inpatients with inpatients who engaged in (verbal and physical) violent behavior.
      Binary logistic regression analyses were used to examine which variables
      contributed independently to the risk of violence. The results showed that
      absconding during treatment was independently associated with physical violence.
      A personality disorder diagnosis and general non-compliance with treatment were
      associated with verbal violence. Both types of violence predicted early
      termination of treatment. Contrary to previous research, the results from the
      risk assessment tools were not associated with inpatient violence. Clinical
      implications are discussed and include, among others, that clinicians should
      remain vigilant for early warning signs of non-compliance during treatment.

PMID- 27708196
TI  - Who Gets Protection? A National Study of Multiple Victimization and Child
      Protection Among Taiwanese Children.
AB  - This study aims to examine the prevalence of multiple types of child
      victimization and the effects of multiple types of victimization on children's
      mental health and behavior in Taiwan. The study also examines the child
      protection rate and its correlates among children experiencing various types of
      victimization. This study collected data with a self-report questionnaire from a
      national proportionately stratified sample of 6,233 fourth-grade students
      covering every city and county in Taiwan in 2014. After calculating the 1-year
      prevalence of child victimization, the study found that bullying was the most
      prevalent (71%), followed by physical neglect (66%), psychological violence
      (43%), inter-parental violence (28%), community violence (22%), physical abuse
      (21%), and sexual violence (9%). As the number of victimization types increased,
      children were more likely to report greater posttraumatic symptoms, psychiatric
      symptoms, suicide ideation, self-harm thoughts, and violent behaviors. Gender,
      neonatal status, parental marital status, and other family risks were
      significantly associated with elevated incidences of the victimization types.
      Only 20.6% of the children who had experienced all seven types of victimization
      had received child protective services. A child was more likely to receive child
      protective services if he or she had experienced sexual violence, community
      violence, inter-parental violence exposure, higher family risks, higher suicidal
      ideation, or living in a single-parent or separated family. In conclusion, this
      study demonstrates the cumulative effects and the harmful effects that children's
      experience of multiple types of victimization can have on the children's mental
      health and behavior. The present findings also raise alarms regarding the
      severity of under-serving in child-victimization cases. These results underscore
      the importance of assessing, identifying, and helping children with multiple
      victimization experiences.

PMID- 27708197
TI  - Influence of Study Design on Developmental and Reproductive Toxicology Study
      Outcomes.
AB  - Regulatory studies of developmental and reproductive toxicity (DART) studies have
      remained largely unchanged for decades, with exposures occurring at various
      phases of the reproductive cycle and toxicity evaluations at different ages/times
      depending on the study purpose. The National Toxicology Program has conducted
      studies examining the power to detect adverse effects where there is a prenatal
      exposure, but evaluations occur postnatally. In these studies, examination is
      required of only 1 male and female pup from each litter beyond weaning. This
      provides poor resolving power to detect rare events (e.g., reproductive tract
      malformations). If an adverse effect is detected, there is little confidence in
      the shape of the dose-response curve (and the Benchmark Dose or No Observed
      Adverse Effect Level [NOAEL]). We have developed a new protocol to evaluate DART,
      the modified one generation study, with exposure commencing with pregnant animals
      and retention of 4 males and females from each litter beyond weaning to improve
      statistical power. These animals can be allocated to specific cohorts that
      examine subchronic toxicity, teratology, littering, and neurobehavioral toxicity
      in the same study. This approach also results in a reduction in animal numbers
      used, compared with individual stand-alone studies, and offers increased numbers
      of end points evaluated compared with recent Organization for Economic
      Cooperation and Development proposals.

PMID- 27708198
TI  - A Synopsis of the "Influence of Epigenetics, Genetics, and Immunology" Session
      Part A at the 35th Annual Society of Toxicologic Pathology Symposium.
AB  - The overarching theme of the 2016 Society of Toxicology Pathology's Annual
      Symposium was "The Basis and Relevance of Variation in Toxicologic Responses."
      Session 4 focused on genetic variation as a potential source for variability in
      toxicologic responses within nonclinical toxicity studies and further explored
      how knowledge of genetic traits might enable targeted prospective and
      retrospective studies in drug development and human health risk assessment. In
      this session, the influence of both genetic sequence variation and epigenetic
      modifications on toxicologic responses and their implications for understanding
      risk were explored. In this overview, the presentations in this session will be
      summarized, with a goal of exploring the ramifications of genetic and epigenetic
      variability within and across species for toxicity studies and disseminating
      information regarding novel tools to harness this variability to advance
      understanding of toxicologic responses across populations.

PMID- 27708199
TI  - Black Eschars in the Highlands of Ethiopia.

PMID- 27708201
TI  - Ozena with Leprosy: United States, 1980.

PMID- 27708203
TI  - Statement of Ownership, Management, and Circulation.

PMID- 27708204
TI  - Evidence for the efficacy of immunotherapy in children with high-risk
      neuroblastoma.
AB  - Neuroblastoma is the most common extra-cranial malignancy of childhood, with the
      highest incidence in children younger than 4 years. The prognosis depends on many
      factors, such as age at diagnosis, stage of disease and molecular genetic
      subtype. More than 50% of children who present with the disease are deemed to
      have high-risk neuroblastoma. The standard therapy for children with high-risk
      neuroblastoma consists of intensive chemotherapy, surgery, radiotherapy,
      myeloablative consolidation with autologous haematopoietic stem cell rescue
      followed by the treatment of minimal residual disease with 13-cis-retinoic acid.
      Unfortunately, more than half of the patients relapse regardless of the treatment
      intensity. Combined therapy with monoclonal antibodies (anti-GD2), intravenous
      interleukin-2 (Il-2), intravenous granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and oral 13-cis-retinoic acid have been proved to be effective in
      some randomised trials. A better understanding of the underlying immunological
      processes in therapy with anti-GD2 antibodies will allow its success to be
      evaluated more accurately and direct future endeavours. Nevertheless, the long
      term benefit of this treatment approach needs to be established.

PMID- 27708205
TI  - The classification, structure and functioning of Ago proteins in Eukaryotes.
AB  - Ago proteins are members of the highly specialized and conserved Argonaute
      family, primarily responsible for regulation of gene expression. As a part of RNA
      induced silencing complexes (RISCs) Ago proteins are responsible for binding a
      short RNA and cleavage/inhibition of translation of target mRNAs. Phosphorylation
      may work as the switch between those two functions, but the role of magnesium ion
      concentration is also taken into consideration. Recent reports indicate that Ago
      proteins can interact with an mRNA and cause inhibition of translation without
      the participation of a short RNA. As key elements in RNA interference processes,
      Ago proteins are an important and intensively exploited area of research.
      Furthermore, these proteins are involved in the repair of DNA double-strand
      breaks by homologous recombination, modifications of chromatin, and alternative
      splicing. Their role in the cell cycle and senescence is also being studied. In
      addition, Ago expression is tissue-specific, which potentially may be used for
      diagnostic purposes. Understanding the mechanisms of Ago functioning is therefore
      crucial for understanding many cellular processes. The following article presents
      a detailed description of the Ago proteins including their post-translational
      modifications, recent data and hypotheses concerning their interactions with
      short RNAs and mRNAs as well as the mechanisms of siRNA/miRNA sorting into
      individual members of the Ago subfamily, and their role in eukaryotic cells. The
      latest classification of Ago proteins within the Argonaute family based on
      evolutionary studies and their possible interactions with DNA are also described.

PMID- 27708206
TI  - Short-term exposure to ambient fine particulate matter (PM2,5 and PM10) and the
      risk of heart rhythm abnormalities and stroke.
AB  - Results of epidemiological studies suggest a significant impact of ambient
      particulate matter air pollution (PM10 and PM2,5) on the health of the
      population. Increased level of these pollutants is connected with increased rate
      of daily mortality and hospitalizations due to cardiovascular diseases. Among
      analyzed health effects, heart arrhythmias and stroke are mentioned most
      frequently. The aim of the study was to present the current knowledge of
      potential influence of the exposure to fine particulate matter on the presence of
      arrhythmias and strokes. Subject literature review suggests, that there is a link
      between short-term exposure to fine dust and the occurrence of arrhythmias.
      Results of previous studies indicates that this exposure may lead to significant
      electrophysiological changes in heart, resulting in higher susceptibility to
      cardiac rhythm abnormalities. In case of stroke, a stronger correlation between
      number of hospitalizations and death cases and exposure to fine dust was seen for
      ischaemic stroke than for haemorhhagic stroke. In addition, a significantly more
      harmful impact of the exposure to ultra particles (particles of aerodynamic
      diameter below 2,5 MUm) has been confirmed. Among important mechanisms
      responsible for observed health impact of particulate matter there are: induction
      and intensification of inflammation, increased oxidative stress, increased
      autonomic nervous system activity, vasoconstriction, rheological changes and
      endothelial dysfunction. Among people of higher susceptibility to fine dust
      negative health impact are: elderly (over 65 years old), obese people, patients
      with respiratory and cardiovascular diseases, patients with diabetes and those
      with coagulation disorders. For further improvement of general health status,
      actions aimed at reducing the risk associated with fine dust and at the same time
      at continuing studies to clarify the biological mechanisms explaining the
      influence of fine dust on human health are necessary.

PMID- 27708207
TI  - Role of oncogene 24p3 neutrophil gelatinase-associated lipocalin (NGAL) in
      digestive system cancers.
AB  - Neutrophil gelatinase-associated lipocalin, known also as 24p3 lipocalin,
      lipocalin-2 or uterocalin (in mouse), is a small secretory protein binding small
      molecular weight ligands which takes part in numerous processes including
      apoptosis induction in leukocytes, iron transport, smell, and prostaglandins and
      retinol transport [19]. It was discovered in activated neutrophils as a covalent
      peptide associated with human gelatinase neutrophils [7]. Neutrophil lipocalin is
      secreted physiologically in the digestive system, respiratory tract, renal
      tubular cells, liver or immunity system. Systematic (circulated in plasma)
      neutrophil gelatinase come from multiple sources; it may be synthesized in the
      liver, secreted from activated neutrophils or macrophages, or derive from
      atherosclerosis or inflammatory endothelial cells [17]. NGAL is stored
      secondarily in granulates with lactoferrin, calprotectin or MAC-1, which take
      part in neutrophils' action and migration [13,19]. NGAL participates in acute and
      chronic inflammation (production of NGAL is indicated by factors conducive to
      cancer progression) [13,21]. NGAL levels increase in inflammatory or endothelial
      damage. NGAL level is measured in blood or urine. It is known as a kidney failure
      factor [7,20]. NGAL is therefore one of the most promising new generation
      biomarkers in clinical nephrology [6]. The role of NGAL in digestive system
      neoplasms has not been explored in detail. However, overexpression of this marker
      was proved in neoplasms such as esophageal carcinoma, stomach cancer, pancreatic
      cancer or colon cancer, which may indicate an association between concentration
      and neoplasm [3].

PMID- 27708208
TI  - Vaccines in prophylaxis of urinary tract infections caused by the bacteria from
      the genus Proteus.
AB  - Urinary tract infections (UTIs) pose a threat especially to women, the
      individuals with weakened immunity or with abnormalities in the urinary tract as
      well as to hospitalized and catheterized patients. The bacteria from the genus
      Proteus, especially P. mirabilis, are important UTI pathogenic factors. They
      frequently cause chronic, recurrent or severely complicated infections, resulting
      in the urinary stones production due to urease and other virulence factors. The
      ability to survive inside the stones and the increasing antibiotic resistance
      make it difficult to eradicate the bacteria from the urinary tract. A good
      solution to the problem may be the vaccination which obtained the interest from
      the surveyed persons, in spite of the antivaccination attitudes visible also in
      Poland. Currently, there are four vaccines available, composed of killed cells of
      different uropathogens, including Proteus spp. They are administrated
      intranassaly or vaginally and require many booster doses. They decrease the
      probability of reinfection in patients suffering from recurrent UTIs but the
      mechanisms of the immune response have not been exactly defined. Promising
      results were obtained in the studies on a mice model concerning the subunit,
      conjugated vaccines in which various P. mirabilis surface antigens (with the
      exception of flagellin) were successfully employed. Hitherto, the best results
      were obtained by the intranasal vaccinations, using MR/P fimbriae antigens with
      MPL or cholera toxin adjuvants and the antigens expressed in Lactococcus lactis
      or Salmonella Typhimurium. It led to an increase in the levels of the specific
      serum and mucosal antibodies resulting in the protection against P. mirabilis
      UTIs.

PMID- 27708209
TI  - PD1/PD1L pathway, HLA-G and T regulatory cells as new markers of
      immunosuppression in cancers.
AB  - The appropriate function of the immune system depends on the effective regulation
      of the immune response on multiple levels. The key element of an effective immune
      response to antigenic stimulation is maintaining a homeostasis between activation
      and inhibitory function of immunocompetent cells and molecules. In pathological
      conditions such as chronic infections, autoimmune diseases or cancer there are
      significant alterations, and prevalence of signals of one type over another. Main
      markers of these dysfunctions are altered expressions of molecules, such as
      programmed death-1 (PD-1), Human Leukocyte Antigen G (HLA-G), or changed
      percentages of T regulatory cells (Treg). These indicators of immune system
      dysfunction may contribute to disease progression, but also could represent good
      targets for treatment. Interestingly, in recent years there are many new,
      interesting reports which showed that the role of PD-1, HLA-G or Treg is
      ambiguous and not always their higher expression or frequency lead to the
      progression of disease. Recent studies have shown that Treg can suppress bacteria
      driven inflammation which promotes carcinogenesis and thus protect the host from
      cancer development. Moreover, proliferation of hematological tumor cells
      expressing ILT-2 receptor can be inhibited by HLA-G, in contrast to solid tumors
      where HLA-G favors tumor escape. In this paper we present characteristics of
      expressions of PD-1 and its ligands, HLA-G, and frequency of Treg cells in a
      variety of physiological and pathological conditions associated with chronic
      infections, autoimmune diseases and cancer. The understanding of the complex
      interactions between the functional elements of immune system is essential for a
      detailed characteristics of the mechanisms leading to the development of diseases
      and identification of more effective targeted therapies.

PMID- 27708210
TI  - Immunoregulatory action of melatonin. The mechanism of action and the effect on
      inflammatory cells.
AB  - Literature data indicate a significant immunoregulatory role of melatonin.
      Melatonin exerts an effect directly affecting leucocytes bearing specific
      melatonin receptors or indirectly by means of melatonin regulating other
      hormones, opioids or cytokines. Despite numerous experiments, the influence of
      the hormone on the immune system is still controversial. Melatonin affects the
      immune response acting as both an activator and an inhibitor of the inflammatory
      process. The hormone acts as an "immunological buffer" activating impaired
      immunity in immunosuppression, chronic stress or old age as well as suppressing
      overreaction of the immune system. Melatonin mediates between neurohormonal and
      immune systems by means of the immune-pineal axis acting as a negative feedback
      mechanism. The axis connects development of the immune reaction with pineal
      activity and melatonin secretion induced by inflammatory mediators. The seasonal
      and circadian fluctuation of the melatonin level and the fluctuation related
      changes of the immune parameters can be responsible for some autoimmune and
      infectious diseases. In spite of that, there is a growing number of papers
      suggesting considerable therapeutic potential of melatonin in inflammatory
      disease treatment. This paper presents well-systematized information on the
      mechanism of melatonin action and its influence on cells involved in the
      inflammatory process - neutrophils and monocytes.

PMID- 27708211
TI  - Can mutations in the gene encoding transcription factor EKLF (Erythroid Kruppel
      Like Factor) protect us against infectious and parasitic diseases?
AB  - Transcription factor EKLF (Erythroid Kruppel-Like Factor) belongs to the group of
      Kruppellike factors, which regulate proliferation, differentiation, development
      and apoptosis of mammalian cells. EKLF factor is present in erythroid cells,
      where it participates in regulation of hematopoiesis, expression of genes
      encoding transmembrane proteins (including blood group antigens), and heme
      biosynthesis enzymes. It is also a key factor in downregulation of gamma-globins
      and activation of beta-globin gene expression. The EKLF factor consists of two
      domains: proline-rich transactivation domain and DNA-binding domain containing
      three zinc finger motifs, which recognize DNA. EKLF can act as a transcription
      activator (for example in the case of beta-globin gene) or repressor, which
      depends on the type of posttranslational modification (phosphorylation,
      SUMOylation, ubiquitination and acetylation). Mutations in the gene encoding EKLF
      may cause hemoglobinopathies, such as hereditary persistence of fetal hemoglobin
      and beta-thalassemia intermedia, and congenital dyserythropoietic anemia type IV,
      which is a hematopoietic disorder. These changes may impede invasion of red blood
      cells by malaria merozoites and cause faster removal of invaded erythrocytes. In
      addition, mutations in KLF1 may decrease the number of erythrocyte surface
      antigens that belong to blood group systems such as MN, P1PK, Lutheran, Duffy,
      Diego and OK. Such antigens can be receptors for protozoans (such as Plasmodium
      falciparum or Plasmodium vivax), bacteria (like uropathogenic strains of
      Escherichia coli, Neisseria meningitidis), and toxins (Shiga toxins), which may
      cause several dangerous diseases including malaria, pyelonephritis, hemorrhagic
      colitis, hemolytic uremic syndrome (HUS) and meningitis. Here, we propose a
      hypothesis on possible liaisons between mutations in the gene encoding EKLF and
      resistance to pathogens.

PMID- 27708212
TI  - Paxillin and its role in the aging process of skin cells.
AB  - Morphology of senescent cells is constantly changing at the molecular level,
      which in turn leads to disruption of their function. It is connected with reduced
      ability to synthesize extracellular matrix (ECM) and leads to the dysfunction of
      integrin adhesion molecules and adhesion clusters. In skin, these factors cause a
      loss of communication between the extracellular matrix and fibroblasts. This
      contributes to the appearance of signs of aging. The aim of this study is to draw
      attention to the very important molecule such as paxillin, which is an adaptor
      protein with mass of 68 kDa. This family of proteins includes Hic-5, PaxB and
      leupaxin. Paxillin binds to actin-binding proteins such as vinculin, actopaxin,
      and kinases (e.g. Integrin-linked kinase (ILK)). Moreover, it plays an important
      role in the integrity of the matrix, because it transduces transmembrane
      signaling between integrins and growth factors. Paxillin is a scaffold protein,
      activating the arrangement and organization of the cytoskeleton. Signaling
      through paxillin affects the long-term changes in gene expression, cell
      proliferation, and organization of the ECM. Correct functioning of the ECM is
      important for the wound healing processes and regeneration of tissues or tissue
      repair. Decrease or lack of paxillin expression results in changes in the
      structure and integrity of the ECM, which are manifested by aging of cells and
      organs. Restoration of the cellular matrix connections would be a significant
      element in the processes related to the anti-aging activities.

PMID- 27708213
TI  - Resistance to PARP inhibitors by SLFN11 inactivation can be overcome by ATR
      inhibition.
AB  - Poly(ADP-ribose) polymerase inhibitors (PARPIs) kill cancer cells by trapping
      PARP1 and PARP2. Talazoparib, the most potent PARPI inhibitor (PARPI), exhibits
      remarkable selectivity among the NCI-60 cancer cell lines beyond BRCA
      inactivation. Our genomic analyses reveal high correlation between response to
      talazoparib and Schlafen 11 (SLFN11) expression. Causality was established in
      four isogenic SLFN11-positive and -negative cell lines and extended to olaparib.
      Response to the talazoparib-temozolomide combination was also driven by SLFN11
      and validated in 36 small cell lung cancer cell lines, and in xenograft models.
      Resistance in SLFN11-deficient cells was caused neither by impaired drug
      penetration nor by activation of homologous recombination. Rather, SLFN11 induced
      irreversible and lethal replication inhibition, which was independent of ATR
      mediated S-phase checkpoint. The resistance to PARPIs by SLFN11 inactivation was
      overcome by ATR inhibition, mechanistically because SLFN11-deficient cells solely
      rely on ATR activation for their survival under PARPI treatment. Our study
      reveals that SLFN11 inactivation, which is common (~45%) in cancer cells, is a
      novel and dominant resistance determinant to PARPIs.

PMID- 27708214
TI  - Novel nomograms for survival and progression in HPV+ and HPV- oropharyngeal
      cancer: a population-based study of 1,542 consecutive patients.
AB  - BACKGROUND: No study has combined tumour and clinical covariates for survival to
      construct an individual risk-profile for overall survival (OS), time to
      progression (TTP), and survival after progression (SAP) in patients with HPV+ and
      HPV- oropharyngeal squamous cell carcinoma (OPSCC). Based on the largest-to-date,
      unselected, population-based cohort of patients diagnosed with OPSCC, we
      performed a comprehensive analysis of long-term OS, TTP, and SAP and constructed
      novel nomograms to evaluate patients' prognoses. RESULTS: At a median follow-up
      of 4.0 years (range: 0.8-15.8 yrs.), 690 deaths were recorded. The 5-year OS,
      TTP, and SAP for the HPV+/p16+ subgroup were 77%, 82%, and 33, vs. 30%, 66%, and
      6% for the HPV-/p16- group (P < 0.01). 376 patients failed to maintain disease
      control with a median TTP of 13 months in the HPV+/p16+ subgroup vs. 8.5 months
      in the HPV-/p16- subgroup (P < 0.05). HPV combined with p16 status remained one
      of the most informative covariates in the final Cox regression model for OS, TTP,
      and SAP. METHODS: We included all patients diagnosed with OPSCC (n = 1,542)
      between 2000-2014 in Eastern Denmark. Survival rates were estimated by the Kaplan
      Meier method. A multivariate Cox regression model was used to construct
      predictive, internally validated nomograms. CONCLUSION: The HPV+/p16+ subgroup
      had improved OS, TTP, and SAP compared with other combinations of HPV and p16
      after adjusting for covariates. Nomograms were constructed for 1-, 5- and 10-year
      survival probability. Models may aid patients and clinicians in their clinical
      decision making as well as in counselling, research, and trial design.

PMID- 27708215
TI  - DACT2 silencing by promoter CpG methylation disrupts its regulation of epithelial
      to-mesenchymal transition and cytoskeleton reorganization in breast cancer cells.
AB  - Wnt signaling plays an important role in breast carcinogenesis. DAPPER2 (DACT2)
      functions as an inhibitor of canonical Wnt signaling and plays distinct roles in
      different cell contexts, with its role in breast tumorigenesis unclear. We
      investigated DACT2 expression in breast cancer cell lines and primary tumors, as
      well as its functions and molecular mechanisms. Results showed that DACT2
      expression was silenced in 9/9 of cell lines. Promoter CpG methylation of DACT2
      was detected in 89% (8/9) of cell lines, as well as in 73% (107/147) of primary
      tumors, but only in 20% (1/5) of surgical margin tissues and in none of normal
      breast tissues. Demethylation of BT549 and T47D cell lines with 5-aza-2'
      deoxycytidine restored DACT2 expression along with promoter demethylation,
      suggesting that its downregulation in breast cancer is dependent on promoter
      methylation. Furthermore, ectopic expression of DACT2 induced breast cell
      apoptosis in vitro, and further inhibited breast tumor cell proliferation,
      migration and EMT, through antagonizing Wnt/beta-catenin and Akt/GSK-3 signaling.
      Thus, these results demonstrate that DACT2 functions as a tumor suppressor for
      breast cancer but was frequently disrupted epigenetically in this cancer.

PMID- 27708217
TI  - The role of surgical intervention in primary colorectal lymphoma: A SEER
      population-based analysis.
AB  - BACKGROUND: Primary colorectal lymphoma (PCL) is a rare colorectal malignancy.
      The standard treatment and prognostic factors of PCL remain unexplored.
      Therefore, a large population-based study should be conducted to provide a
      detailed review of this disease. METHODS: We extracted the data of eligible
      patients with PCL registered in the SEER database from 1973 to 2011. All
      statistical analyses were performed using SPSS 19.0. RESULTS: A total of 2050
      (61.3%) of the 3342 patients with PCL underwent surgical intervention, and 1292
      (38.7%) patients received no surgical treatment. The median overall survival was
      95 months, and patients receiving surgery exhibited significantly prolonged
      survival (adjusted HR =0.69, P <0.001). Young age, early tumor stage, and
      indolent lymphoma were independent predictors of improved survival. Further
      survival analyses demonstrated the potential benefit of surgery in patients with
      early tumor stage, right-sided lesions, or diffuse large B-cell PCL. Conversely,
      surgical intervention did not improve the survival of patients with advanced
      stage, left-sided, or indolent PCL. CONCLUSION: PCL is a rare tumor that can be
      effectively treated. Surgical intervention may play an important role in the
      treatment of PCL. Early tumor stage, a right-sided lesion, and diffuse large B
      cell histological PCL seem to be the clinical characteristics of optimal surgical
      candidates.

PMID- 27708216
TI  - Smoking-associated lung cancer prevention by blockade of the beta-adrenergic
      receptor-mediated insulin-like growth factor receptor activation.
AB  - Activation of receptor tyrosine kinases (RTKs) is associated with carcinogenesis,
      but its contribution to smoking-associated lung carcinogenesis is poorly
      understood. Here we show that a tobacco-specific carcinogen 4-(methylnitrosamino)
      1-(3-pyridyl)-1-butanone (NNK)-induced insulin-like growth factor 1 receptor (IGF
      1R) activation via beta-adrenergic receptor (beta-AR) is crucial for smoking
      associated lung carcinogenesis. Treatment with NNK stimulated the IGF-1R
      signaling pathway in a time- and dose-dependent manner, which was suppressed by
      pharmacological or genomic blockade of beta-AR and the downstream signaling
      including a Gbetagamma subunit of beta-AR and phospholipase C (PLC).
      Consistently, beta-AR agonists led to increased IGF-1R phosphorylation. The
      increase in IGF2 transcription via beta-AR, signal transducer and activator of
      transcription 3 (STAT3), and nuclear factor-kappa B (NF-kappaB) was associated
      with NNK-induced IGF-1R activation. Finally, treatment with beta-AR antagonists
      suppressed the acquisition of transformed phenotypes in lung epithelial cells and
      lung tumor formation in mice. These results suggest that blocking beta-AR
      mediated IGF-1R activation can be an effective strategy for lung cancer
      prevention in smokers.

PMID- 27708218
TI  - Overexpression of caveolin-1 attenuates brain edema by inhibiting tight junction
      degradation.
AB  - Cerebral edema from the disruption of the blood-brain barrier (BBB) after
      cerebral ischemia is a major cause of morbidity and mortality as well as a common
      event in patients with stroke. Caveolins (Cavs) are thought to regulate BBB
      functions. Here, we report for the first time that Cav-1 overexpression (OE)
      decreased brain edema from BBB disruption following ischemic insult. Edema
      volumes and Cav-1 expression levels were measured following photothrombosis and
      middle cerebral artery occlusion (MCAO). Endothelial cells that were transduced
      with a Cav-1 lentiviral expression vector were transplanted into rats. BBB
      permeability was quantified with Evans blue extravasation. Edema volume was
      determined from measures of the extravasation area, brain water content, and
      average fluorescence intensity after Cy5.5 injections. Tight junction (TJ)
      protein expression was measured with immunoblotting. Cav-1 expression levels and
      vasogenic brain edema correlated strongly after ischemic insult. Cav-1 expression
      and BBB disruption peaked 3 d after the MCAO. In addition, intravenous
      administration of endothelial cells expressing Cav-1 effectively increased the
      Cav-1 levels 3 d after the MCAO ischemic insult. Importantly, Cav-1 OE
      ameliorated the vasogenic edema by inhibiting the degradation of TJ protein
      expression in the acute phase of ischemic stroke. These results suggested that
      Cav-1 OE protected the integrity of the BBB mainly by preventing the degradation
      of TJ proteins in rats. These findings need to be confirmed in a clinical setting
      in human subjects.

PMID- 27708219
TI  - A small deletion in SERPINC1 causes type I antithrombin deficiency by promoting
      endoplasmic reticulum stress.
AB  - Antithrombin (AT) deficiency is an autosomal dominant disorder, and
      identification of mutation AT variants would improve our understanding of the
      anticoagulant function of this serine protease inhibitor (SERPIN) and the
      molecular pathways underlying this disorder. In the present study, we performed
      whole-exome sequencing of a Chinese family with deep vein thrombosis, and
      identified a new small deletion that eliminates four amino acids (INEL) from exon
      4 of SERPINC1 gene. This causes type I AT deficiency by enhancing the
      intracellular retention of this protein. AT retention leads to endoplasmic
      reticulum (ER) stress, which further inhibits AT release. In addition, ER stress
      activates ER-associated degradation, which promotes AT degradation. Suppression
      of ER stress enhanced the secretion of AT, while inhibition of ER-associated
      degradation suppressed AT release. Thus, our study identified a new mutation
      (INEL deletion) causing type I AT deficiency, and uncovered a novel mechanism for
      AT retention through enhanced ER stress, which may provide an innovative approach
      for treating AT deficiency.

PMID- 27708220
TI  - Myocardin-related transcription factor A (MRTF-A) activity-dependent cell
      adhesion is correlated to focal adhesion kinase (FAK) activity.
AB  - The regulation of cell-substrate adhesion is tightly linked to the malignant
      phenotype of tumor cells and plays a role in their migration, invasion, and
      metastasis. Focal adhesions (FAs) are dynamic adhesion structures that anchor the
      cell to the extracellular matrix. Myocardin-related transcription factors
      (MRTFs), co-regulators of the serum response factor (SRF), regulate expression of
      a set of genes encoding actin cytoskeletal/FA-related proteins. Here we
      demonstrated that the forced expression of a constitutively active MRTF-A (CA
      MRTF-A) in B16F10 melanoma cells induced the up-regulation of actin cytoskeletal
      and FA proteins, resulting in FA reorganization and the suppression of cell
      migration. Expression of CA-MRTF-A markedly increased phosphorylation of focal
      adhesion kinase (FAK) and paxillin, which are important components for FA
      dynamics. Notably, FAK activation was triggered by the clustering of up-regulated
      integrins. Our results revealed that the MRTF-SRF-dependent regulation of cell
      migration requires both the up-regulation of actin cytoskeletal/FA proteins and
      the integrin-mediated regulation of FA components via the FAK/Src pathway. We
      also demonstrated that activation of the MRTF-dependent transcription correlates
      FAK activation in various tumor cells. The elucidation of the correlation between
      MRTF and FAK activities would be an effective therapeutic target in focus of
      tumor cell migration.

PMID- 27708221
TI  - PRMT5 competitively binds to CDK4 to promote G1-S transition upon glucose
      induction in hepatocellular carcinoma.
AB  - Although cancer cells are known to be "addicted" to glucose, the effect of
      glucose in proliferation of these cells remains elusive. Here, we report that
      upon glucose induction, protein arginine methyltransferase 5 (PRMT5) exerts a
      profound effect on the G1-S cell cycle progression via directly interacting with
      cyclin dependent kinase 4 (CDK4) in hepatocellular carcinoma (HCC). Upregulation
      of both PRMT5 and CDK4 predicts more malignant characteristics in human HCC
      tissues. Mechanistically, glucose promotes the interaction between PRMT5 and
      CDK4, which leads to activation of CDK4-RB-E2F-mediated transcription via
      releasing CDKN2A from CDK4. Moreover, the PRMT5 competitive inhibition of the
      interaction between CDK4 and CDKN2A is important for glucose-induced growth of
      HCC cells. Furthermore, the CDK4 mutant R24A weakly binds to PRMT5, inhibiting
      HCC cell cycle progression and tumor growth. Thus, our findings uncover a
      critical function for PRMT5 and CDK4 and provide an improved therapeutic strategy
      against HCC.

PMID- 27708223
TI  - Differential effects of peptidoglycan on colorectal tumors and intestinal tissue
      post-pelvic radiotherapy.
AB  - Immediate medical intervention is required after pelvic tumor radiotherapy to
      protect the radiosensitive intestine and also to mitigate tumor growth. Toll-like
      receptors (TLRs) have been shown to promote tissue repair processes. Here, we
      analyzed the effect observed upon combining the TLR2 agonist, peptidoglycan
      (PGN), with radiation therapy on tumors as well as intestinal tissue, both in
      vitro and in vivo. In contrast to radiotherapy alone, PGN when combined with
      ionizing radiation (IR) elicited enhanced antitumor effects and also reduced the
      IR-induced intestinal damage. Mechanistic studies showed that PGN first induced
      an IL13 response in the irradiated intestine, but was decreased in tumor cell
      models screened by Th1/Th2 FlowCytomix assay and validated by the application of
      IL13 and anti-IL13 neutralizing antibodies. Next, PGN stimulated Akt3, but not
      Akt1/2, as was verified by AKT1/2/3 plasmid transfection assay and in AKT1/2/3
      knockout mice in vivo. Akt3 expression was inhibited in 20 MUg/mL PGN-treated
      tumor cells and in 1.5 mg/kg PGN-treated mouse tumor models. However, Akt3 was
      raised via IL13 in the irradiated intestine and human intestinal cell line after
      the same treatment. Finally, PGN activated mTOR via IL13/AKT3 in the intestine
      and restored intestinal structure and function. As an adjuvant to radiotherapy,
      PGN inhibited tumorigenesis by suppression of mTOR activity. To summarize, the
      IL13/AKT3/mTOR pathway was lessened in PGN-treated irradiated tumors but was
      raised in the normal intestine tissue. This distinct effect of PGN on normal and
      tumor tissues during pelvic radiotherapy suggests that PGN may be a promising
      adjuvant therapy to radiation.

PMID- 27708222
TI  - Epithelial cells captured from ductal carcinoma in situ reveal a gene expression
      signature associated with progression to invasive breast cancer.
AB  - Breast cancer biomarkers that can precisely predict the risk of progression of
      non-invasive ductal carcinoma in situ (DCIS) lesions to invasive disease are
      lacking. The identification of molecular alterations that occur during the
      invasion process is crucial for the discovery of drivers of transition to
      invasive disease and, consequently, biomarkers with clinical utility. In this
      study, we explored differences in gene expression in mammary epithelial cells
      before and after the morphological manifestation of invasion, i.e., early and
      late stages, respectively. In the early stage, epithelial cells were captured
      from both pre-invasive lesions with distinct malignant potential [pure DCIS as
      well as the in situ component that co-exists with invasive breast carcinoma
      lesions (DCIS-IBC)]; in the late stage, epithelial cells were captured from the
      two distinct morphological components of the same sample (in situ and invasive
      components). Candidate genes were identified using cDNA microarray and rapid
      subtractive hybridization (RaSH) cDNA libraries and validated by RT-qPCR assay
      using new samples from each group. These analyses revealed 26 genes, including 20
      from the early and 6 from the late stage. The expression profile based on the 20
      genes, marked by a preferential decrease in expression level towards invasive
      phenotype, discriminated the majority of DCIS samples. Thus, this study revealed
      a gene expression signature with the potential to predict DCIS progression and,
      consequently, provides opportunities to tailor treatments for DCIS patients.

PMID- 27708224
TI  - A module of inflammatory cytokines defines resistance of colorectal cancer to
      EGFR inhibitors.
AB  - Epidermal Growth Factor Receptor (EGFR) activates a robust signalling network to
      which colon cancer tumours often become addicted. Cetuximab, one of the
      monoclonal antibodies targeting this pathway, is employed to treat patients with
      colorectal cancer. However, many patients are intrinsically refractory to this
      treatment, and those who respond develop secondary resistance along time.
      Mechanisms of cancer cell resistance include either acquisition of new mutations
      or non genomic activation of alternative signalling routes. In this study, we
      employed a colon cancer model to assess potential mechanisms driving resistance
      to cetuximab. Resistant cells displayed increased ability to grow in suspension
      as colonspheres and this phenotype was associated with poorly organized
      structures. Factors secreted from resistant cells were causally involved in
      sustaining resistance, indeed administration to parental cells of conditioned
      medium collected from resistant cells was sufficient to reduce cetuximab
      efficacy. Among secreted factors, we report herein that a signature of
      inflammatory cytokines, including IL1A, IL1B and IL8, which are produced
      following EGFR pathway activation, was associated with the acquisition of an
      unresponsive phenotype to cetuximab in vitro. This signature correlated with lack
      of response to EGFR targeting also in patient-derived tumour xenografts.
      Collectively, these results highlight the contribution of inflammatory cytokines
      to reduced sensitivity to EGFR blockade and suggest that inhibition of this panel
      of cytokines in combination with cetuximab might yield an effective treatment
      strategy for CRC patients refractory to anti-EGFR targeting.

PMID- 27708226
TI  - Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer
      cells via the ROS-activated GCN2-eIF2alpha-ATF4-xCT pathway.
AB  - Mitochondrial DNA mutations and defects in mitochondrial enzymes have been
      identified in gastric cancers, and they might contribute to cancer progression.
      In previous studies, mitochondrial dysfunction was induced by oligomycin-enhanced
      chemoresistance to cisplatin. Herein, we dissected the regulatory mechanism for
      mitochondrial dysfunction-enhanced cisplatin resistance in human gastric cancer
      cells. Repeated cisplatin treatment-induced cisplatin-resistant cells exhibited
      high SLC7A11 (xCT) expression, and xCT inhibitors (sulfasalazine or erastin), xCT
      siRNA, or a GSH synthesis inhibitor (buthionine sulphoximine, BSO) could
      sensitize these cells to cisplatin. Clinically, the high expression of xCT was
      associated with a poorer prognosis for gastric cancer patients under adjuvant
      chemotherapy. Moreover, we found that mitochondrial dysfunction enhanced
      cisplatin resistance and up-regulated xCT expression, as well as intracellular
      glutathione (GSH). The xCT inhibitors, siRNA against xCT or BSO decreased
      mitochondrial dysfunction-enhanced cisplatin resistance. We further demonstrated
      that the upregulation of the eIF2alpha-ATF4 pathway contributed to mitochondrial
      dysfunction-induced xCT expression, and activated eIF2alpha kinase GCN2, but not
      PERK, stimulated the eIF2alpha-ATF4-xCT pathway in response to mitochondrial
      dysfunction-increased reactive oxygen species (ROS) levels. In conclusion, our
      results suggested that the ROS-activated GCN2-eIF2alpha-ATF4-xCT pathway might
      contribute to mitochondrial dysfunction-enhanced cisplatin resistance and could
      be a potential target for gastric cancer therapy.

PMID- 27708225
TI  - NSAID-activated gene 1 mediates pro-inflammatory signaling activation and
      paclitaxel chemoresistance in type I human epithelial ovarian cancer stem-like
      cells.
AB  - Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in
      developed countries. Chronic endogenous sterile pro-inflammatory responses are
      strongly linked to EOC progression and chemoresistance to anti-cancer
      therapeutics. In the present study, the activity of epithelial NF-kappaB, a key
      pro-inflammatory transcription factor, was enhanced with the progress of EOC.
      This result was mechanistically linked with an increased expression of NSAID
      Activated Gene 1 (NAG-1) in MyD88-positive type I EOC stem-like cells, compared
      with that in MyD88-negative type II EOC cells. Elevated NAG-1 as a potent
      biomarker of poor prognosis in the ovarian cancer was positively associated with
      the levels of NF-kappaB activation, chemokines and stemness markers in type I EOC
      cells. In terms of signal transduction, NAG-1-activated SMAD-linked and non
      canonical TGFbeta-activated kinase 1 (TAK-1)-activated pathways contributed to NF
      kappaB activation and the subsequent induction of some chemokines and cancer
      stemness markers. In addition to effects on NF-kappaB-dependent gene regulation,
      NAG-1 was involved in expression of EGF receptor and subsequent activation of EGF
      receptor-linked signaling. The present study also provided evidences for links
      between NAG-1-linked signaling and chemoresistance in ovarian cancer cells. NAG-1
      and pro-inflammatory NF-kappaB were positively associated with resistance to
      paclitaxel in MyD88-positive type I EOC cells. Mechanistically, this
      chemoresistance occurred due to enhanced activation of the SMAD-4- and non-SMAD
      TAK-1-linked pathways. All of the present data suggested NAG-1 protein as a
      crucial mediator of EOC progression and resistance to the standard first-line
      chemotherapy against EOC, particularly in MyD88-positive ovarian cancer stem-like
      cells.

PMID- 27708227
TI  - T-cell responses against CD19+ pediatric acute lymphoblastic leukemia mediated by
      bispecific T-cell engager (BiTE) are regulated contrarily by PD-L1 and CD80/CD86
      on leukemic blasts.
AB  - T-cell immunotherapies are promising options in relapsed/refractory B-precursor
      acute lymphoblastic leukemia (ALL). We investigated the effect of co-signaling
      molecules on T-cell attack against leukemia mediated by CD19/CD3-bispecific T
      cell engager. Primary CD19+ ALL blasts (n>=10) and physiologic CD19+CD10+ bone
      marrow precursors were screened for 20 co-signaling molecules. PD-L1, PD-1, LAG
      3, CD40, CD86, CD27, CD70 and HVEM revealed different stimulatory and inhibitory
      profiles of pediatric ALL compared to physiologic cells, with PD-L1 and CD86 as
      most prominent inhibitory and stimulatory markers. PD-L1 was increased in
      relapsed ALL patients (n=11) and in ALLs refractory to Blinatumomab (n=5).
      Exhaustion markers (PD-1, TIM-3) were significantly higher on patients' T cells
      compared to physiologic controls. T-cell proliferation and effector function was
      target-cell dependent and correlated to expression of co-signaling molecules.
      Blockade of inhibitory PD-1-PD-L and CTLA-4-CD80/86 pathways enhanced T-cell
      function whereas blockade of co-stimulatory CD28-CD80/86 interaction
      significantly reduced T-cell function. Combination of Blinatumomab and anti-PD-1
      antibody was feasible and induced an anti-leukemic in vivo response in a 12-year
      old patient with refractory ALL. In conclusion, ALL cells actively regulate T
      cell function by expression of co-signaling molecules and modify efficacy of
      therapeutic T-cell attack against ALL. Inhibitory interactions of leukemia
      induced checkpoint molecules can guide future T-cell therapies.

PMID- 27708228
TI  - SIRT1-mediated downregulation of p27Kip1 is essential for overcoming contact
      inhibition of Kaposi's sarcoma-associated herpesvirus transformed cells.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus associated
      with Kaposi's sarcoma (KS), a malignancy commonly found in AIDS patients. Despite
      intensive studies in the last two decades, the mechanism of KSHV-induced cellular
      transformation and tumorigenesis remains unclear. In this study, we found that
      the expression of SIRT1, a metabolic sensor, was upregulated in a variety of KSHV
      infected cells. In a model of KSHV-induced cellular transformation, SIRT1
      knockdown with shRNAs or knockout by CRISPR/Cas9 gene editing dramatically
      suppressed cell proliferation and colony formation in soft agar of KSHV
      transformed cells by inducing cell cycle arrest and contact inhibition. SIRT1
      knockdown or knockout induced the expression of cyclin-dependent kinase inhibitor
      1B (p27Kip1). Consequently, p27 knockdown rescued the inhibitory effect of SIRT1
      knockdown or knockout on cell proliferation and colony formation. Furthermore,
      treatment of KSHV-transformed cells with a SIRT1 inhibitor, nicotinamide (NAM),
      had the same effect as SIRT1 knockdown and knockout. NAM significantly inhibited
      cell proliferation in culture and colony formation in soft agar, and induced cell
      cycle arrest. Significantly, NAM inhibited the progression of tumors and extended
      the survival of mice in a KSHV-induced tumor model. Collectively, these results
      demonstrate that SIRT1 suppression of p27 is required for KSHV-induced
      tumorigenesis and identify a potential therapeutic target for KS.

PMID- 27708229
TI  - Prognostic effect of intratumoral neutrophils across histological subtypes of non
      small cell lung cancer.
AB  - Recent data indicate that tumor-associated neutrophils (TANs) serve a dual role
      in tumor progression and regression. CD66b is a neutrophil marker and has been
      associated with patient outcome in various cancers. However, its clinical impact
      in non-small cell lung cancer (NSCLC) remains controversial. 536 NSCLC patients,
      of which 172 harbored lymph node metastases, were included in this study. Tissue
      microarrays were constructed and multiplexed immunohistochemistry of CD66b, CD34
      and pan-keratin was performed to evaluate the localization and quantity of CD66b+
      TANs. High intratumoral CD66b+ TANs density in squamous cell carcinoma (SCC)
      subgroup was an independent positive prognosticator for disease-specific survival
      (P = 0.038). In contrast, high intratumoral TANs density was an independent
      negative prognostic factor in the adenocarcinoma (ADC) subgroup (P= 0.032).
      Likewise, in ADC patients with lymph node metastases, high level of intratumoral
      TANs was associated with poor prognosis (P = 0.003). Stromal CD66b+ TANs were not
      associated with outcome of NSCLC patients. In conclusion, CD66b+ TANs show
      diverging prognostic effect in NSCLC patients according to histological
      subgroups. The presence of CD66b+ TANs could prove pivotal for development of an
      immunoscore in ADC NSCLC patients.

PMID- 27708230
TI  - Cytomorphological characteristics of glassy cell carcinoma of the uterine cervix:
      histopathological correlation and human papillomavirus genotyping.
AB  - A retrospective analysis was performed to describe the cytomorphological and
      histopathological findings and human papillomavirus (HPV) genotypes for glassy
      cell carcinoma (GCC) of the uterine cervix. Five cases of cervical GCC, in which
      the glassy cell features constituted at least 95% of the specimen, were included.
      Four patients had stage IIB GCCs and one had stage IIIB GCC. All patients
      underwent concurrent chemoradiation therapy. Based on pretreatment cytology, only
      1 of the 5 cases was correctly diagnosed as GCC. The remaining cases were
      diagnosed as carcinoma of undetermined type, adenocarcinoma, poorly
      differentiated carcinoma, or unsatisfactory for evaluation. Cytological specimens
      had moderate cellularity and contained small clusters of tumor cells admixed with
      amphophilic, granular tumor diathesis. The tumor cells possessed large, round to
      oval nuclei and abundant, granular, ground-glass cytoplasm. The nuclei exhibited
      prominent eosinophilic nucleoli. The cytoplasm displayed sharp margins and
      molding, resulting in "intercellular windows" between neighboring attached cells.
      HPV genotyping revealed that high-risk HPV types 18, 16, and 31 were detected in
      3, 1, and 1 cases, respectively. Consistent with this finding, all cases
      exhibited block p16 positivity, confirming the association of HPV infection with
      GCC. In conclusion, a distinct cytoplasmic margin, the characteristic
      histopathological feature of GCC, was observed in liquid-based cytological
      preparations. We suggest that sharp cytoplasmic outlines with molding and
      intercellular windows are characteristic cytomorphological features of GCC.
      Detection of high-risk HPV in all cases strongly supported the notion that high
      risk HPV is involved in the pathogenesis of GCC.

PMID- 27708231
TI  - Deregulation of the pRb-E2F4 axis alters epidermal homeostasis and favors tumor
      development.
AB  - E2F/RB activity is altered in most human tumors. The retinoblastoma family of
      proteins plays a key role in regulating the progression of the cell cycle from
      the G1 to S phases. This is achieved through negative regulation of E2F
      transcription factors, important positive regulators of cell cycle entry. E2F
      family members are divided into two groups: activators (E2F1-E2F3a) and
      repressors (E2F3b-E2F8). E2F4 accounts for a large part of the E2F activity and
      is a main E2F repressor member in vivo. Perturbations in the balance from
      quiescence towards proliferation contribute to increased mitotic gene expression
      levels frequently observed in cancer. We have previously reported that combined
      Rb1-Rbl1 or Rb1-E2f1 ablation in epidermis produces important alterations in
      epidermal proliferation and differentiation, leading to tumor development.
      However, the possible roles of E2F4 in this context are still to be determined.
      Here, we show the absence of any discernible phenotype in the skin of mice
      lacking of E2f4. In contrast, the inducible loss of Rb1 in the epidermis of E2F4
      null mice produced multiple skin abnormalities including altered differentiation
      and proliferation, spontaneous wounds, carcinoma in situ development and stem
      cell perturbations. All these phenotypic alterations are associated with
      extensive gene expression changes, the induction of c-myc and the Akt activation.
      Moreover the whole transcriptome analyses in comparison with previous models
      generated also revealed extensive changes in multiple repressive complexes and in
      transcription factor activity. These results point to E2F4 as a master regulator
      in multiple steps of epidermal homeostasis in Rb1 absence.

PMID- 27708232
TI  - A strong host response and lack of MYC expression are characteristic for diffuse
      large B cell lymphoma transformed from nodular lymphocyte predominant Hodgkin
      lymphoma.
AB  - Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma,
      but can transform into diffuse large B cell lymphoma (DLBCL), showing a more
      aggressive clinical behavior. Little is known about these cases on the molecular
      level. Therefore, the aim of the present study was to characterize DLBCL
      transformed from NLPHL (LP-DLBCL) by gene expression profiling (GEP). GEP
      revealed an inflammatory signature pinpointing to a specific host response. In a
      coculture model resembling this host response, DEV tumor cells showed an impaired
      growth behavior. Mechanisms involved in the reduced tumor cell proliferation
      included a downregulation of MYC and its target genes. Lack of MYC expression was
      also confirmed in 12/16 LP-DLBCL by immunohistochemistry. Furthermore, CD274/PD
      L1 was upregulated in DEV tumor cells after coculture with T cells or monocytes
      and its expression was validated in 12/19 cases of LP-DLBCL. Thereby, our data
      provide new insights into the pathogenesis of LP-DLBCL and an explanation for the
      relatively low tumor cell content. Moreover, the findings suggest that treatment
      of these patients with immune checkpoint inhibitors may enhance an already
      ongoing host response in these patients.

PMID- 27708233
TI  - Advanced lung adenocarcinomas with ROS1-rearrangement frequently show hepatoid
      cell.
AB  - Defining distinctive histologic characteristics of ROS1-rearranged non-small-cell
      lung carcinomas (NSCLCs) may help identify cases that merit molecular testing.
      However, the majority of previous reports have focused on surgical specimens but
      only limited studies assessed histomorphology of advanced NSCLCs. In order to
      identify the clinical and histological characteristics of ROS1-rearranged
      advanced NSCLCs, we examined five hundred sixteen Chinese patients with advanced
      NSCLCs using ROS1 fluorescence in situ hybridization and real-time polymerase
      chain reaction and then analyzed for clinical and pathological features. We
      performed univariate and multivariate analyses to identify predictive factors
      associated with ROS1 rearrangement. 19 tumors were identified with ROS1
      rearrangement (3.7% of adenocarcinomas). 16 ROS1+ and 122 ROS1- samples with
      available medical records and enough tumor cells were included for histological
      analysis. Compared with ROS1-negative advanced NSCLCs,ROS1-rearranged advanced
      NSCLCs were associated with a younger age at presentation. ROS1 rearrangements
      were not significantly associated with sex, smoking history, drinking history and
      metastatic sites. The most common histological pattern was solid growth (12/16),
      followed by acinar (4/16) growth. 66.7% cases with solid growth pattern showed
      hepatoid cytology (8/12) and 75% cases with acinar growth pattern showed a
      cribriform structure (3/4). 18.8% cases were found to have abundant extracellular
      mucus or signet-ring cells (3/16). Only one case with solid growth pattern showed
      psammomatous calcifications. In conclusion, age, hepatoid cytology and cribriform
      structure are the independent predictors for ROS1-rearranged advanced NSCLCs,
      recognizing these may be helpful in finding candidates for genomic alterations,
      especially when available tissue samples are limited.

PMID- 27708234
TI  - Plasma and tumor levels of Linc-pint are diagnostic and prognostic biomarkers for
      pancreatic cancer.
AB  - Long intergenic non-protein coding RNA, p53 induced transcript (Linc-pint) is a
      long noncoding RNA (lncRNA) that regulates tumor cell viability and
      proliferation. We used qRT-PCR and RNA FISH analysis to evaluate Linc-pint levels
      in the plasma and tumor tissues of pancreatic cancer (PCa) patients. Our data
      demonstrate that Linc-pint expression is lower in plasma samples from PCa
      patients than from healthy individuals, and indicate that plasma Linc-pint levels
      are more sensitive than CA19-9 for detecting PCa. Our data also show that Linc
      pint levels are lower in PCa tumors than in adjacent tissues, carcinoma of the
      ampulla of Vater (CAV) and cholangiocarcinoma (CCA), and suggest that Linc-pint
      could be used for distinguishing the cause of malignant obstructive jaundice. Low
      plasma Linc-pint levels correlate with tumor recurrence, while low tumor Linc
      pint levels correlate with poor prognosis for PCa patients after pancreatectomy.
      These results thus indicate that low plasma Linc-pint expression could serve as a
      minimally invasive biomarker for early PCa detection, and that low Linc-pint
      levels in PCa tumors could be used for predicting patient prognosis.

PMID- 27708235
TI  - A next-generation bifunctional photosensitizer with improved water-solubility for
      photodynamic therapy and diagnosis.
AB  - Photodynamic therapy (PDT) exploits light interactions and photosensitizers to
      induce cytotoxic reactive oxygen species. Photodynamic diagnosis (PDD) uses the
      phenomenon of photosensitizer emitting fluorescence to distinguish some tumors
      from normal tissue. The standard photosensitizer used for PDD is 5-aminolevulinic
      acid (5-ALA), although it is not entirely satisfactory. We previously reported
      glucose-conjugated chlorin (G-chlorin) as a more effective photosensitizer than
      another widely used photosensitizer, talaporfin sodium (TS); however, G-chlorin
      is hydrophobic. We synthesized oligosaccharide-conjugated chlorin (O-chlorin)
      with improved water-solubility. We report herein on its accumulation and
      cytotoxicity. O-chlorin was synthesized and examined for solubility. Flow
      cytometric analysis was performed to evaluate O-chlorin accumulation in cancer
      cells. To evaluate the intracellular localization of photosensitizer, cells were
      stained with O-chlorin and organelle-specific fluorescent probes. We then
      measured the in vitro fluorescence of various photosensitizers and the half
      maximal inhibitory concentrations to evaluate effects in PDD and PDT,
      respectively. Xenograft tumor models were established, and antitumor and
      visibility effects were analyzed. O-chlorin was first shown to be hydrophilic.
      Flow cytometry then revealed a 20- to 40-times higher accumulation of O-chlorin
      in cancer cells than of TS, and a 7- to 23-times greater fluorescence than 5-ALA.
      In vitro, the cytotoxicity of O-chlorin PDT was stronger than that of TS PDT, and
      O-chlorin tended to accumulate in lysosomes. In vivo, O-chlorin showed the best
      effect in PDT and PDD compared to other photosensitizers.O-chlorin was
      hydrophilic and showed excellent tumor accumulation and fluorescence. O-chlorin
      is promising as a next-generation bifunctional photosensitizer candidate for both
      PDT and PDD.

PMID- 27708236
TI  - Engineering of double recombinant vaccinia virus with enhanced oncolytic
      potential for solid tumor virotherapy.
AB  - Vaccinia virus (VACV) oncolytic therapy has been successful in a number of tumor
      models. In this study our goal was to generate a double recombinant vaccinia
      virus (VV-GMCSF-Lact) with enhanced antitumor activity that expresses exogenous
      proteins: the antitumor protein lactaptin and human granulocyte-macrophage colony
      stimulating factor (GM-CSF). Lactaptin has previously been demonstrated to act as
      a tumor suppressor in mouse hepatoma as well as MDA-MB-231 human adenocarcinoma
      cells grafted into SCID mice. VV-GMCSF-Lact was engineered from Lister strain (L
      IVP) vaccinia virus and has deletions of the viral thymidine kinase and vaccinia
      growth factor genes. Cell culture experiments revealed that engineered VV-GMCSF
      Lact induced the death of cultured cancer cells more efficiently than recombinant
      VACV coding only GM-CSF (VV-GMCSF-dGF). Normal human MCF-10A cells were resistant
      to both recombinants up to 10 PFU/cell. The selectivity index for breast cancer
      cells measured in pair cultures MCF-7/MCF-10A was 200 for recombinant VV-GMCSF
      Lact coding lactaptin and 100 for VV-GMCSF-dGF. Using flow cytometry we
      demonstrated that both recombinants induced apoptosis in treated cells but that
      the rate in the cells with active caspase-3 and -7 was higher after treatment
      with VV-GMCSF-Lact than with VV-GMCSF-dGF. Tumor growth inhibition and survival
      outcomes after VV-GMCSF-Lact treatment were estimated using immunodeficient and
      immunocompetent mice models. We observed that VV-GMCSF-Lact efficiently delays
      the growth of sensitive and chemoresistant tumors. These results demonstrate that
      recombinant VACVs coding an apoptosis-inducing protein have good therapeutic
      potential against chemoresistant tumors. Our data will also stimulate further
      investigation of coding lactaptin double recombinant VACV in clinical settings.

PMID- 27708237
TI  - Proteomic identification of the lactate dehydrogenase A in a radioresistant
      prostate cancer xenograft mouse model for improving radiotherapy.
AB  - Radioresistance is a major challenge for prostate cancer (CaP) metastasis and
      recurrence after radiotherapy. This study aimed to identify potential protein
      markers and signaling pathways associated with radioresistance using a PC-3
      radioresistant (RR) subcutaneous xenograft mouse model and verify the
      radiosensitization effect from a selected potential candidate. PC-3RR and PC-3
      xenograft tumors were established and differential protein expression profiles
      from two groups of xenografts were analyzed using liquid chromatography tandem
      mass spectrometry. One selected glycolysis marker, lactate dehydrogenase A (LDHA)
      was validated, and further investigated for its role in CaP radioresistance. We
      found that 378 proteins and 51 pathways were significantly differentially
      expressed between PC-3RR and PC-3 xenograft tumors, and that the glycolysis
      pathway is closely linked with CaP radioresistance. In addition, we also
      demonstrated that knock down of LDHA with siRNA or inhibition of LDHA activity
      with a LDHA specific inhibitor (FX-11), could sensitize PC-3RR cells to
      radiotherapy with reduced epithelial-mesenchymal transition, hypoxia, DNA repair
      ability and autophagy, as well as increased DNA double strand breaks and
      apoptosis. In summary, we identified a list of potential RR protein markers and
      important signaling pathways from a PC-3RR xenograft mouse model, and demonstrate
      that targeting LDHA combined with radiotherapy could increase radiosensitivity in
      RR CaP cells, suggesting that LDHA is an ideal therapeutic target to develop
      combination therapy for overcoming CaP radioresistance.

PMID- 27708238
TI  - Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer
      growth in mice.
AB  - Endometrial cancer is the most common cancer in women, typically with onset after
      menopause. Isoliquiritigenin (ISL), a licorice flavonoid, was previously shown to
      have anti-oxidant, anti-inflammatory, and tumor suppression effects. In this
      study, we investigated the anti-tumor effect of ISL on human endometrial cancer
      both in vitro and in vivo. We used telomerase-immortalized human endometrial
      stromal cells (T-HESCs) and human endometrial cancer cell lines (Ishikawa, HEC
      1A, and RL95-2 cells) as targets. The effects of ISL on cell proliferation, cell
      cycle regulation, and apoptosis or autophagy-related protein expression were
      examined. In addition, we conducted in vivo experiments to confirm the inhibitory
      effects of ISL on cancer cells. ISL significantly inhibited the viability of
      cancer cells in a dose- and time-dependent manner but with little toxicity on
      normal cells. In addition, flow cytometry analysis indicated that ISL induced sub
      G1 or G2/M phase arrest. ISL treatment activated the extracellular signal
      regulated kinase signaling pathway to enhance the protein expression of caspase
      7/LC3BII associated with apoptosis/autophagy. Furthermore, ISL suppressed
      xenograft tumor growth in vivo. Taken together, these findings suggest that ISL
      may induce apoptosis, autophagy, and cell growth inhibition, indicating its
      potential as a therapeutic agent for human endometrial cancer.

PMID- 27708240
TI  - Overexpression and potential roles of NRIP1 in psoriasis.
AB  - Nuclear receptor interacting protein 1 (NRIP1, also known as RIP140) is a co
      regulator for various transcriptional factors and nuclear receptors, and has been
      shown to take part in many biological and pathological processes, such as
      regulating mammary gland development and inflammatory response.The aim of this
      study is to investigate the expression of NRIP1 and to explore its roles in the
      pathogenesis of psoriasis. Thirty active psoriasis patients and 16 healthy
      volunteers were enrolled for this study. qRT-PCR analyses found that both NRIP1
      and RelA/p65 were elevated in psoriatic lesions compared to psoriatic non-lesions
      and normal controls, and also overexpressed in peripheral blood mononuclear cell
      (PBMCs) of psoriasis patients. Suppression of NRIP1 in HaCaT cells could
      significantly inhibit cell growth and induce apoptosis, and the suppression of
      NRIP1 in CD4+ T cells isolated from psoriasis patients could downregulate the
      expression of RelA/p65 and decrease the secretion of IL-17. Furthermore, in Nrip1
      knockout mice, IMQ-induced inflammation of skin was delayed and the RelA/p65
      expression in lesions was reduced. In conclusion, our data suggests that NRIP1 is
      overexpressed both in skin and PBMCs of psoriasis patients and may be involved in
      the abnormal proliferation and apoptosis of keratinocytes, as well as the immune
      reaction through the regulation of RelA/p65. Therefore, NRIP1 may be a potential
      therapeutic target for psoriasis.

PMID- 27708239
TI  - FOXC1 identifies basal-like breast cancer in a hereditary breast cancer cohort.
AB  - Breast cancers arising in the setting of the hereditary breast cancer genes BRCA1
      and BRCA2 are most commonly classified as basal-like breast cancer (BLBC) or
      luminal breast cancer, respectively. BLBC is an aggressive subtype of breast
      cancer associated with liver and lung metastases and poorer prognosis than other
      subtypes and for which chemotherapy is the only systemic therapy. Multiple
      immunohistochemical markers are used to identify the basal-like subtype,
      including the absence of estrogen receptor alpha, progesterone receptor, and
      human epidermal growth factor receptor 2. Forkhead box C1 (FOXC1) has been
      identified as a specific marker expressed in BLBC in general breast cancer
      cohorts. We examined an institutional cohort of breast cancer patients with
      germline BRCA1 (n=46) and BRCA2 (n=35) mutations and found that FOXC1 expression
      on immunohistochemical staining is associated with BRCA1 vs BRCA2 mutations
      [30/46 vs. 6/35]. In BRCA1 mutant tumors, FOXC1 was expressed in 28/31 BLBC
      tumors and 2/13 non-BLBC tumors, In BRCA2 mutant tumors, FOXC1 was expressed in
      5/5 BLBC tumors and 1/30 non-BLBC tumors. In cell culture models of BRCA1-mutant
      breast cancer, FOXC1 is associated with increased proliferation and may serve as
      a marker for sensitivity to PARP-inhibitor therapy with olaparib.

PMID- 27708241
TI  - Hepatitis B virus X induces inflammation and cancer in mice liver through
      dysregulation of cytoskeletal remodeling and lipid metabolism.
AB  - Hepatitis B virus X protein (HBx) participates in the occurrence and development
      processes of hepatocellular carcinoma (HCC) as a multifunctional regulation
      factor. However, the underlying molecular mechanism remains obscure. Here, we
      describe the use of p21HBx/+ mouse and SILAM (Stable Isotope Labeling in Mammals)
      strategy to define the pathological mechanisms for the occurrence and development
      of HBx induced liver cancer. We systematically compared a series of proteome
      samples from regular mice, 12- and 24-month old p21HBx/+ mice representing the
      inflammation and HCC stages of liver disease respectively and their nontransgenic
      wild-type (WT) littermates. Totally we identified 22 and 97 differentially
      expressed proteins out of a total of 2473 quantified proteins. Bioinformatics
      analysis suggested that the lipid metabolism and CDC42-induced cytoskeleton
      remodeling pathways were strongly activated by the HBx transgene. Interestingly,
      the protein-protein interaction MS study revealed that HBx directly interacted
      with multiple proteins in these two pathways. The same effect of up-regulation of
      cytoskeleton and lipid metabolism related proteins, including CDC42, CFL1,
      PPARgamma and ADFP, was also observed in the Huh-7 cells transfected with HBx.
      More importantly, CFL1 and ADFP were specifically accumulated in HBV-associated
      HCC (HBV-HCC) patient samples, and their expression levels were positively
      correlated with the severity of HBV-related liver disease. These results provide
      evidence that HBx induces the dysregulation of cytoskeleton remodeling and lipid
      metabolism and leads to the occurrence and development of liver cancer. The CFL1
      and ADFP might be served as potential biomarkers for prognosis and diagnosis of
      HBV-HCC.

PMID- 27708242
TI  - Early responses of EGFR circulating tumor DNA to EGFR tyrosine kinase inhibitors
      in lung cancer treatment.
AB  - OBJECTIVES: Early evaluation of the effect of treatment is helpful in the
      management of cancer patients. Circulating biomarkers are an ideal tool for this
      if they are highly specific to tumors and respond rapidly to tumor volume
      changes. Circulating tumor DNA (ctDNA) is one such candidate. We conducted a
      prospective study to test the utility of EGFR ctDNA in early evaluation of EGFR
      TKI effects. RESULTS: Twenty-one patients with EGFR-mutant lung cancer who were
      naive to EGFR-TKI were enrolled. PM scores of EGFR ctDNA with activating
      mutations decreased rapidly in response to EGFR-TKI. Of the 14 patients with
      positive pretreatment PM scores, complete disappearance of major EGFR ctDNA was
      observed in 14.3%, 42.9%, and 57.1% on days 2 - 4, 8, and 15, respectively. These
      responses of EGFR ctDNA were most prominent among the measures used to evaluate
      responses, and correlated with early radiologic responses evaluated by chest X
      rays. MATERIALS AND METHODS: EGFR ctDNA in serial plasma samples was amplified
      and 105 copies were sequenced with a next-generation sequencer. Plasma mutation
      (PM) score was defined as the number of reads containing deletions/substitutions
      in 105EGFR cell free DNA (cfDNA). When EGFR mutation in ctDNA was the same as
      that detected in cancer tissue, the ctDNA was defined as major EGFR ctDNA.
      CONCLUSIONS: The results indicate the usefulness of ctDNA as a highly specific
      biomarker for prediction of early response to treatment and that it can be
      applied to various types of cancer.

PMID- 27708243
TI  - JWA down-regulates HER2 expression via c-Cbl and induces lapatinib resistance in
      human gastric cancer cells.
AB  - Human epidermal growth factor receptor 2 (HER2) targeted therapy is currently
      considered as the standard treatment for HER2-positive advanced gastric cancer
      (GC). However, unsatisfactory results of recent phase III clinical trials
      involving lapatinib suggested biomarkers for selection of patients. The aim of
      this study was to identify JWA as a biomarker for lapatinib resistance in GC
      cells and elucidate the underlying mechanisms. Lapatinib was effective to the
      intrinsic cisplatin-resistant GC cells. JWA activation conferred lapatinib
      unresponsiveness, but reversed cisplatin resistance in GC cells. Whereas,
      deletion of JWA significantly restored lapatinib suppression on proliferation and
      lapatinib-induced apoptosis. JWA-induced down-regulation of HER2 and activation
      of ERK phosphorylation led to lapatinib resistance. Furthermore, c-Cbl
      represented a novel mechanism for HER2 degradation enhanced by JWA in GC cells.
      Taken together, JWA is a potential predictive marker for lapatinib resistance,
      targeting the patients that may benefit from lapatinib treatment in human GC.

PMID- 27708244
TI  - Hypoxia pathway and hypoxia-mediated extensive extramedullary hematopoiesis are
      involved in ursolic acid's anti-metastatic effect in 4T1 tumor bearing mice.
AB  - Hypoxic in the tumor mass is leading to the myeloproliferative-like disease
      (leukemoid reaction) and anemia of body, which characterized by strong extensive
      extramedullary hematopoiesis (EMH) in spleen. As the key transcription factor of
      hypoxia, hypoxia-inducible factor-1 (HIF-1) activates the expression of genes
      essential for EMH processes including enhanced blood cell production and
      angiogenesis. We found ursolic acid (UA), a natural pentacyclic triterpenoid
      carboxylic acid, inhibited growth of breast cancer both in vivo and in vitro. The
      suppression was mediated through the inhibition of multiple cell pathways linked
      to inflammation, proliferation, angiogenesis, and metastasis. UA also suppressed
      the leukemoid reaction and the EMH phenomenon of the tumor bearing mice without
      any significant suppression on body weight (i.p. by 20 mg/kg for 28 days). This
      is associated with the significant decrease in white blood cells (WBC), platelets
      (PLT) and spleen weight. During this process, we also detected the down
      regulation of cell proliferative genes (PCNA, and beta-catenin), and metastatic
      genes (VEGF, and HIF-1alpha), as well as the depression of nuclear protein
      intensity of HIF-1alpha. Furthermore, the expression of E2F1, p53 and MDM2 genes
      were increased in UA group when the VEGF and HIF-1alpha was over-expressed.
      Cancer cells were sensitive to UA treating after the silencing of HIF-1alpha and
      the response of Hypoxic pathway reporter to UA was suppressed when HIF-1alpha was
      over expressed. Overall, our results from experimental and predictive studies
      suggest that the anticancer activity of UA may be at least in part caused by
      suppressing the cancer hypoxia and hypoxia-mediated EMH.

PMID- 27708245
TI  - Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome
      in the ApoE-/- Alzheimer's mouse model.
AB  - Accruing data indicate that radiation-induced consequences resemble pathologies
      of neurodegenerative diseases such as Alzheimer's. The aim of this study was to
      elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure
      (1 mGy/day or 20 mGy/day) given over 300 days with cumulative doses of 0.3 Gy and
      6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an
      Alzheimer's model. Using mass spectrometry, a marked alteration in the
      phosphoproteome was found at both dose rates. The radiation-induced changes in
      the phosphoproteome were associated with the control of synaptic plasticity,
      calcium-dependent signalling and brain metabolism. An inhibition of CREB
      signalling was found at both dose rates whereas Rac1-Cofilin signalling was found
      activated only at the lower dose rate. Similarly, the reduction in the number of
      activated microglia in the molecular layer of hippocampus that paralleled with
      reduced levels of TNFalpha expression and lipid peroxidation was significant only
      at the lower dose rate. Adult neurogenesis, investigated by Ki67, GFAP and NeuN
      staining, and cell death (activated caspase-3) were not influenced at any dose or
      dose rate. This study shows that several molecular targets induced by chronic low
      dose-rate radiation overlap with those of Alzheimer's pathology. It may suggest
      that ionising radiation functions as a contributing risk factor to this
      neurodegenerative disease.

PMID- 27708246
TI  - A novel DNA methylation score accurately predicts death from prostate cancer in
      men with low to intermediate clinical risk factors.
AB  - Clinically aggressive disease behavior is difficult to predict in men with low to
      intermediate clinical risk prostate cancer and methylation biomarkers may be a
      valuable adjunct for assessing the management of these patients. We set to
      evaluate the utility of DNA methylation to identify high risk disease in men
      currently considered as low or intermediate risk. DNA was extracted from formalin
      fixed paraffin-embedded transurethral prostate resection tissues collected during
      the years 1990-96 in a watchful-waiting cohort of men in the UK. The primary end
      point was death of prostate cancer, assessed by reviewing cancer registry records
      from 2009. Methylation was quantified by pyrosequencing assays for six genes
      (HSPB1, CCND2, TIG1, DPYS, PITX2, and MAL) with established biomarker value in
      prostate cancer. A novel prognostic methylation score was developed by
      multivariate Cox modelling using the six methylation biomarkers in 385 men with
      low-and-intermediate clinical risk variables and its prognostic value compared to
      two previously defined clinically-derived risk scores. Methylation score was the
      most significant variable in univariate and bivariate analysis in men with low-to
      intermediate CAPRA risk score. When combined with CAPRA score the hazard ratio
      was 2.02; 95% confidence interval, 1.40-2.92. For a methylation score sensitivity
      of 83% the specificity was 44%, while the maximum achieved sensitivity by CAPRA
      was 68% at a specificity of 44%. The derived methylation score is a strong
      predictor of aggressive prostate cancer that could have an important role in
      directing the management of patients with low-to-intermediate risk disease. The
      estimated areas under the curve (AUC) at 10 years of follow-up were 0.62 (95% CI:
      0.51, 0.70) and 0.74 (95% CI: 0.65, 0.82) for CAPRA, and combined (CAPRA +
      methylation) risk score (CRS) respectively.

PMID- 27708247
TI  - Scriptaid overcomes hypoxia-induced cisplatin resistance in both wild-type and
      mutant p53 lung cancer cells.
AB  - Non-small cell lung cancer (NSCLC), comprising 85% of lung cancer cases, has been
      associated with resistance to chemo/radiotherapy. The hypoxic tumor micro
      environment, where insufficient vasculature results in poor drug penetrance and
      sub-optimal chemotherapy in the tumor interiors contributes heavily to this
      resistance. Additionally, epigenetic changes in tumorigenic cells also change
      their response to different forms of therapy. In our study, we have investigated
      the effectiveness of a combination of cisplatin with scriptaid [a pan-Histone
      Deacetylase inhibitor (HDACi)] in a model that mimics the tumor microenvironment
      of hypoxia and sub-lethal chemotherapy. Scriptaid synergistically increases the
      efficacy of cisplatin in normoxia as well as hypoxia, accompanied with reduced
      metastasis and enhanced DNA damage. Addition of scriptaid also overcomes the
      cisplatin resistance exhibited in lung cancer cells with stabilized hypoxia
      inducible factor 1 (HIF1)-alpha (mutant) and mutant p53. Molecular studies showed
      that the combination treatment increased apoptotic cell death in both normoxia
      and hypoxia with a dual role of p38MAPK. Together, our results suggest that the
      combination of low dose cisplatin and scriptaid is cytotoxic to NSCLC lines, can
      overcome hypoxia induced resistance and mutant p53- induced instability often
      associated with this cancer, and has the potential to be an effective therapeutic
      modality.

PMID- 27708248
TI  - Distinct biological effects of low-dose radiation on normal and cancerous human
      lung cells are mediated by ATM signaling.
AB  - Low-dose radiation (LDR) induces hormesis and adaptive response in normal cells
      but not in cancer cells, suggesting its potential protection of normal tissue
      against damage induced by conventional radiotherapy. However, the underlying
      mechanisms are not well established. We addressed this in the present study by
      examining the role of the ataxia telangiectasia mutated (ATM) signaling pathway
      in response to LDR using A549 human lung adenocarcinoma cells and HBE135-E6E7
      (HBE) normal lung epithelial cells. We found that LDR-activated ATM was the
      initiating event in hormesis and adaptive response to LDR in HBE cells. ATM
      activation increased the expression of CDK4/CDK6/cyclin D1 by activating the
      AKT/glycogen synthase kinase (GSK)-3beta signaling pathway, which stimulated HBE
      cell proliferation. Activation of ATM/AKT/GSK-3beta signaling also increased
      nuclear accumulation of nuclear factor erythroid 2-related factor 2, leading to
      increased expression of antioxidants, which mitigated cellular damage from
      excessive reactive oxygen species production induced by high-dose radiation.
      However, these effects were not observed in A549 cells. Thus, the failure to
      activate these pathways in A549 cells likely explains the difference between
      normal and cancer cells in terms of hormesis and adaptive response to LDR.

PMID- 27708249
TI  - Downregulation of sphingosine kinase-1 induces protective tumor immunity by
      promoting M1 macrophage response in melanoma.
AB  - The infiltration of melanoma tumors by macrophages is often correlated with poor
      prognosis. However, the molecular signals that regulate the dialogue between
      malignant cells and the inflammatory microenvironment remain poorly understood.
      We previously reported an increased expression of sphingosine kinase-1 (SK1),
      which produces the bioactive lipid sphingosine 1-phosphate (S1P), in melanoma.
      The present study aimed at defining the role of tumor SK1 in the recruitment and
      differentiation of macrophages in melanoma. Herein, we show that downregulation
      of SK1 in melanoma cells causes a reduction in the percentage of
      CD206highMHCIIlow M2 macrophages in favor of an increased proportion of
      CD206lowMHCIIhigh M1 macrophages into the tumor. This macrophage differentiation
      orchestrates T lymphocyte recruitment as well as tumor rejection through the
      expression of Th1 cytokines and chemokines. In vitro experiments indicated that
      macrophage migration is triggered by the binding of tumor S1P to S1PR1 receptors
      present on macrophages whereas macrophage differentiation is stimulated by SK1
      induced secretion of TGF-beta1. Finally, RNA-seq analysis of human melanoma
      tumors revealed a positive correlation between SK1 and TGF-beta1 expression.
      Altogether, our findings demonstrate that melanoma SK1 plays a key role in the
      recruitment and phenotypic shift of the tumor macrophages that promote melanoma
      growth.

PMID- 27708250
TI  - Targeting the ERK pathway for the treatment of Cushing's disease.
AB  - We recently demonstrated that the orphan nuclear receptor testicular receptor 4
      (TR4) is a potent regulator of corticotroph tumor growth and hormone secretion.
      The Ras/Raf/MEK/ERK pathway is commonly overactivated in human tumors and we have
      demonstrated that corticotroph tumor TR4 is activated by ERK1/2-mediated
      phosphorylation. We evaluated effects of MEK-162, a selective, non-ATP
      competitive allosteric inhibitor of MEK1/2, on murine and human in vitro and in
      vivo corticotroph tumor proliferation and adrenocorticotrophic hormone (ACTH)
      secretion. MEK-162 treatment dose-dependently inhibited corticotroph tumor
      proliferation, induced apoptosis, reduced pro-opiomelanocortin (POMC) mRNA levels
      and inhibited ACTH secretion in vitro. Similar findings were obtained in human
      corticotroph tumor primary cultures (n = 5). These actions of MEK-162 were
      augmented in the presence of TR4 overexpression, suggesting that TR4 levels may
      serve as a predictive biomarker of MEK-162 corticotroph tumor responsiveness.
      Additionally, MEK-162 treatment reduced TR4 protein expression and blocked
      recruitment of TR4 to bind its consensus site on the POMC promoter (-854bp to 
      637bp), elucidating multiple mechanisms to control TR4 corticotroph tumor
      actions. In a murine corticotroph tumor in vivo model of Cushing's disease, MEK
      162 treatment inhibited tumor growth and reduced tumor-derived circulating plasma
      ACTH, and corticosterone levels. These results demonstrate the potent actions of
      MEK-162 to inhibit corticotroph tumor growth and hormone secretion in vitro and
      in vivo via TR4-dependent and independent mechanisms, and raise the possibility
      of MEK-162 as a novel therapy for Cushing's disease.

PMID- 27708251
TI  - An open-label, randomized study of the impact on insulin sensitivity, lipid
      profile and vascular inflammation by treatment with lopinavir/ritonavir or
      raltegravir in HIV-negative male volunteers.
AB  - BACKGROUND: We aimed to measure the effect of raltegravir (RAL) on insulin
      sensitivity and surrogates of cardiovascular risk in healthy HIV-seronegative
      volunteers compared to that of lopinavir/r (LPV/r), a positive control. METHODS:
      An open-label, two phase crossover study in HIV-negative male subjects randomized
      1:1 to receive either 2 weeks of LPV/r followed by a 2-week washout period and 2
      weeks of RAL, or RAL initially followed by LPV/r. A hyperinsulinaemic euglycaemic
      clamp was performed prior to and following each 2-week dosing phase. Fasting
      samples for lipids, adiponectin, leptin, vascular inflammatory biomarkers and
      CD36 were also taken. RESULTS: A total of 16 subjects completed the study. At the
      baseline visit the mean insulin-stimulated glucose disposal per unit insulin
      (M/I) was 7.97 and 8.30 for LPV/r and RAL, respectively. The mean (sem)
      percentage change from baseline was -16.10% (3.84) after 2 weeks of LPV/r and 
      0.43% (4.83) after 2 weeks of RAL. Absolute M/I was 25% lower for LPV/r than for
      RAL (P=0.001). Triglycerides and total cholesterol rose significantly with LPV/r
      (+0.5 mmol/l, P=0.002 and +0.4 mmol/l, P<0.0001), but were unchanged with RAL.
      Proathrogenic lipid subfractions of low-density lipoprotein (LDL) cholesterol
      increased with LPV/r and were unaffected with RAL. LDL peak and mean particle
      diameter and LDL I significantly decreased with LPV/r (P<0.05), and trend of
      increased LDL III was detected. High-sensitivity C-reactive protein declined with
      RAL (-0.2 mg/l, P=0.043) but was elevated after LPV/r (+0.25 mg/l, P=0.03).
      CONCLUSIONS: RAL was not associated with measurable change in glycaemic,
      metabolic or inflammatory effects.

PMID- 27708252
TI  - Effects of mir-21 on Cardiac Microvascular Endothelial Cells After Acute
      Myocardial Infarction in Rats: Role of Phosphatase and Tensin Homolog
      (PTEN)/Vascular Endothelial Growth Factor (VEGF) Signal Pathway.
AB  - BACKGROUND This study investigated how miR-21 expression is reflected in acute
      myocardial infarction and explored the role of miR-21 and the PTEN/VEGF signaling
      pathway in cardiac microvascular endothelial cells. MATERIAL AND METHODS We used
      an in vivo LAD rat model to simulate acute myocardial infarction. MiR-21 mimics
      and miR-21 inhibitors were injected and transfected into model rats in order to
      alter miR-21 expression. Cardiac functions were evaluated using echocardiographic
      measurement, ELISA, and Masson staining. In addition, lenti-PTEN and VEGF siRNA
      were transfected into CMEC cells using standard procedures for assessing the
      effect of PTEN and VEGE on cell proliferation, apoptosis, and angiogenesis. MiR
      21, PTEN, and VEGF expressions were examined by RT-PCR and Western blot. The
      relationship between miR-21 and PTEN was determined by the luciferase activity
      assay. RESULTS We demonstrated that miR-21 bonded with the 3'-UTR of PTEN and
      suppressed PTEN expressions. Established models significantly induced cardiac
      infarct volume and endothelial injury marker expressions as well as miR-21 and
      PTEN expressions (P<0.05). MiR-21 mimics exhibited significantly protective
      effects since they down-regulated both infarction size and injury marker
      expressions by increasing VEGF expression and inhibiting PTEN expression
      (P<0.05). In addition, results from in vitro research show that lenti-PTEN and
      VEGF siRNA can notably antagonize the effect of miR-21 on cell proliferation,
      apoptosis, and angiogenesis (P<0.05). CONCLUSIONS MiR-21 exerts protective
      effects on endothelial injury through the PTEN/VEGF pathway after acute
      myocardial infarction.

PMID- 27708253
TI  - Unusual Complication of Pituitary Macroadenoma: A Case Report and Review.
AB  - BACKGROUND Pituitary macroadenoma is a common benign tumor that usually presents
      with visual field defects or hormonal abnormalities. Cerebral infarction can be a
      complication of a large pituitary adenoma. We report a rare case of bilateral
      anterior cerebral arteries infarcts by a large pituitary macroadenoma with
      apoplexy. CASE REPORT A 48-year-old male patient presented with altered conscious
      level and sudden loss of vision for one-day duration. Magnetic resonance imaging
      of the brain showed a large seller and suprasellar hemorrhagic mass of pituitary
      origin, with associated bilateral areas of diffusion restriction in the frontal
      parasagittal regions, consistent with infarctions. Magnetic resonance angiography
      showed elevation and compression of A1 segment of both anterior cerebral arteries
      by the hemorrhagic pituitary macroadenoma. The patient underwent trans-sphenoidal
      resection of the pituitary adenoma, but unfortunately, ischemia was irreversible.
      Computed tomography (CT) done post-operatively showed hypodensity in the frontal
      and parietal parasagittal areas, which was also persistent in the follow up CT
      scans. The patient's neurological function remained poor, with GCS of 8/15, in
      vegetative state. CONCLUSIONS Vascular complications of the pituitary apoplexy,
      although uncommon, can be very severe and life threatening. Early detection of
      vascular compromise caused by hemorrhagic pituitary macroadenoma can prevent
      delay in intervention. Clinicians should also consider pituitary adenoma as a
      possible cause of stroke.

PMID- 27708254
TI  - [Data Analysis of Subacute Patients with Registered Information in the Minimum
      Basic Data Set for Social-Healthcare (CMBD-RSS), Spain].
AB  - OBJECTIVE: It is necessary to deepen in the knowledge of the Basic Minimum Set of
      Data (CMBD-RSS) of patients with chronic pathology associated and frequent
      hospitalisations (the subacute care). The aim of this study was to analyse the
      sanitary information of these patients, once initiated the subacute program.
      METHODS: We used data of 660 patients hospitalised in the subacute care unit at
      the Santa Caterina Hospital, sanitary region of Girona, from October 2013 to
      December 2014. The CMBD data base was analysed using SPSS Statistics 15.0. We
      verified the relationship between variables i.e. length of stay and age; origin
      of the patient admission and length of stay (Mann-Whitney U Test); main diagnosis
      and length of stay (Kruskal-Wallis). We also studied the relationship between
      origin of the patient admission and main diagnosis (Chi-square test and Cramer's
      V). RESULTS: The average age of patients was 83 years old, and mainly female
      profile (55%). Five illnesses concentrated 80% of all patients' diagnosed
      diseases (mental health problems, nervous system diseases, circulatory problems,
      respiratory system problems and genitourinary infections). Patients admitted from
      hospitals had a shorter length of stay (8 days) than patients admitted from home
      (9 days). 80% of cases patients come back home after the hospital discharge.
      CONCLUSIONS: People with chronic pathology associated and frequent
      hospitalisations are an important group of risk. Elderly and clinical
      decompensations add complexity to these cases. The evaluation of these patients
      at the admission and discharge procedures optimise the use of the resources.

PMID- 27708255
TI  - Spiral magnetic order and pressure-induced superconductivity in transition metal
      compounds.
AB  - Magnetic and superconducting ground states can compete, cooperate and coexist.
      MnP provides a compelling and potentially generalizable example of a material
      where superconductivity and magnetism may be intertwined. Using a synchrotron
      based non-resonant X-ray magnetic diffraction technique, we reveal a spiral spin
      order in MnP and trace its pressure evolution towards superconducting order via
      measurements in a diamond anvil cell. Judging from the magnetostriction, ordered
      moments vanish at the quantum phase transition as pressure increases the electron
      kinetic energy. Spins remain local in the disordered phase, and the promotion of
      superconductivity is likely to emerge from an enhanced coupling to residual
      spiral spin fluctuations and their concomitant suppression of phonon-mediated
      superconductivity. As the pitch of the spiral order varies across the 3d
      transition metal compounds in the MnP family, the magnetic ground state switches
      between antiferromagnet and ferromagnet, providing an additional tuning parameter
      in probing spin-fluctuation-induced superconductivity.

PMID- 27708257
TI  - Crystal structures of the human elongation factor eEFSec suggest a non-canonical
      mechanism for selenocysteine incorporation.
AB  - Selenocysteine is the only proteinogenic amino acid encoded by a recoded in-frame
      UGA codon that does not operate as the canonical opal stop codon. A specialized
      translation elongation factor, eEFSec in eukaryotes and SelB in prokaryotes,
      promotes selenocysteine incorporation into selenoproteins by a still poorly
      understood mechanism. Our structural and biochemical results reveal that four
      domains of human eEFSec fold into a chalice-like structure that has similar
      binding affinities for GDP, GTP and other guanine nucleotides. Surprisingly,
      unlike in eEF1A and EF-Tu, the guanine nucleotide exchange does not cause a major
      conformational change in domain 1 of eEFSec, but instead induces a swing of
      domain 4. We propose that eEFSec employs a non-canonical mechanism involving the
      distinct C-terminal domain 4 for the release of the selenocysteinyl-tRNA during
      decoding on the ribosome.

PMID- 27708259
TI  - Efficient and selective N-alkylation of amines with alcohols catalysed by
      manganese pincer complexes.
AB  - Borrowing hydrogen (or hydrogen autotransfer) reactions represent straightforward
      and sustainable C-N bond-forming processes. In general, precious metal-based
      catalysts are employed for this effective transformation. In recent years, the
      use of earth abundant and cheap non-noble metal catalysts for this process
      attracted considerable attention in the scientific community. Here we show that
      the selective N-alkylation of amines with alcohols can be catalysed by defined
      PNP manganese pincer complexes. A variety of substituted anilines are
      monoalkylated with different (hetero)aromatic and aliphatic alcohols even in the
      presence of other sensitive reducible functional groups. As a special highlight,
      we report the chemoselective monomethylation of primary amines using methanol
      under mild conditions.

PMID- 27708258
TI  - Modelling proteins' hidden conformations to predict antibiotic resistance.
AB  - TEM beta-lactamase confers bacteria with resistance to many antibiotics and
      rapidly evolves activity against new drugs. However, functional changes are not
      easily explained by differences in crystal structures. We employ Markov state
      models to identify hidden conformations and explore their role in determining
      TEM's specificity. We integrate these models with existing drug-design tools to
      create a new technique, called Boltzmann docking, which better predicts TEM
      specificity by accounting for conformational heterogeneity. Using our MSMs, we
      identify hidden states whose populations correlate with activity against
      cefotaxime. To experimentally detect our predicted hidden states, we use rapid
      mass spectrometric footprinting and confirm our models' prediction that increased
      cefotaxime activity correlates with reduced Omega-loop flexibility. Finally, we
      design novel variants to stabilize the hidden cefotaximase states, and find their
      populations predict activity against cefotaxime in vitro and in vivo. Therefore,
      we expect this framework to have numerous applications in drug and protein
      design.

PMID- 27708256
TI  - ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and
      degradation.
AB  - Heat shock protein (Hsp)70 is a molecular chaperone that maintains protein
      homoeostasis during cellular stress through two opposing mechanisms: protein
      refolding and degradation. However, the mechanisms by which Hsp70 balances these
      opposing functions under stress conditions remain unknown. Here, we demonstrate
      that Hsp70 preferentially facilitates protein refolding after stress, gradually
      switching to protein degradation via a mechanism dependent on ARD1-mediated Hsp70
      acetylation. During the early stress response, Hsp70 is immediately acetylated by
      ARD1 at K77, and the acetylated Hsp70 binds to the co-chaperone Hop to allow
      protein refolding. Thereafter, Hsp70 is deacetylated and binds to the ubiquitin
      ligase protein CHIP to complete protein degradation during later stages. This
      switch is required for the maintenance of protein homoeostasis and ultimately
      rescues cells from stress-induced cell death in vitro and in vivo. Therefore,
      ARD1-mediated Hsp70 acetylation is a regulatory mechanism that temporally
      balances protein refolding/degradation in response to stress.

PMID- 27708260
TI  - Interplay between evanescence and disorder in deep subwavelength photonic
      structures.
AB  - Deep subwavelength features are expected to have minimal impact on wave
      transport. Here we show that in contrast to this common understanding, disorder
      can have a dramatic effect in a one-dimensional disordered optical system with
      spatial features a thousand times smaller than the wavelength. We examine a
      unique regime of Anderson localization where the localization length is shown to
      scale linearly with the wavelength instead of diverging, because of the role of
      evanescent waves. In addition, we demonstrate an unusual order of magnitude
      enhancement of transmission induced due to localization. These results are
      described for electromagnetic waves, but are directly relevant to other wave
      systems such as electrons in multi-quantum-well structures.

PMID- 27708263
TI  - Unveiling the pentagonal nature of perfectly aligned single-and double-strand Si
      nano-ribbons on Ag(110).
AB  - Carbon and silicon pentagonal low-dimensional structures attract a great interest
      as they may lead to new exotic phenomena such as topologically protected phases
      or increased spin-orbit effects. However, no pure pentagonal phase has yet been
      realized for any of them. Here we unveil through extensive density functional
      theory calculations and scanning tunnelling microscope simulations, confronted to
      key experimental facts, the hidden pentagonal nature of single- and double-strand
      chiral Si nano-ribbons perfectly aligned on Ag(110) surfaces whose structure has
      remained elusive for over a decade. Our study reveals an unprecedented one
      dimensional Si atomic arrangement solely comprising almost perfect alternating
      pentagons residing in the missing row troughs of the reconstructed surface. We
      additionally characterize the precursor structure of the nano-ribbons, which
      consists of a Si cluster (nano-dot) occupying a silver di-vacancy in a quasi
      hexagonal configuration. The system thus materializes a paradigmatic shift from a
      silicene-like packing to a pentagonal one.

PMID- 27708262
TI  - Evaluation of KIR3DL1/KIR3DS1 polymorphism in Behcet's disease.
AB  - The Behcet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA
      B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like
      receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their
      cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested
      whether KIR-regulated mechanisms contribute to BD by testing for association of
      KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy
      controls from Turkey, as well as in different subsets of individuals with HLA
      type-defined ligands for the KIR3D receptors. HLA types were imputed from single
      nucleotide polymorphism genotypes determined with the Immunochip. The presence of
      inhibitory KIR3DL1 or activating KIR3DS1 alleles did not differ significantly
      between cases and controls (KIR3DL1: 92.9% vs 93.4%, Pdominant=0.55; KIR3DS1:
      42.7% vs 41.0%, Pdominant=0.29). The KIR3DL1/KIR3DS1 alleles were also present at
      similar frequencies among cases and controls bearing HLA-B with a Bw4 motif; HLA
      B with a Bw4 motif with isoleucine at position 80; and HLA-B*51. Our results
      suggest that pathogenic mechanisms associated with HLA-B*51 do not primarily
      involve differential interactions with KIR3DL1 and KIR3DS1 receptors. However,
      due to the complexity of this locus (that is, sequence variation and copy number
      variation), we cannot exclude a role for other types of KIR variation in the
      pathogenesis of BD.

PMID- 27708261
TI  - Genome sequence of the basal haplorrhine primate Tarsius syrichta reveals unusual
      insertions.
AB  - Tarsiers are phylogenetically located between the most basal strepsirrhines and
      the most derived anthropoid primates. While they share morphological features
      with both groups, they also possess uncommon primate characteristics, rendering
      their evolutionary history somewhat obscure. To investigate the molecular basis
      of such attributes, we present here a new genome assembly of the Philippine
      tarsier (Tarsius syrichta), and provide extended analyses of the genome and
      detailed history of transposable element insertion events. We describe the
      silencing of Alu monomers on the lineage leading to anthropoids, and recognize an
      unexpected abundance of long terminal repeat-derived and LINE1-mobilized
      transposed elements (Tarsius interspersed elements; TINEs). For the first time in
      mammals, we identify a complete mitochondrial genome insertion within the nuclear
      genome, then reveal tarsier-specific, positive gene selection and posit
      population size changes over time. The genomic resources and analyses presented
      here will aid efforts to more fully understand the ancient characteristics of
      primate genomes.

PMID- 27708264
TI  - Competitive solvent-molecule interactions govern primary processes of
      diphenylcarbene in solvent mixtures.
AB  - Photochemical reactions in solution often proceed via competing reaction pathways
      comprising intermediates that capture a solvent molecule. A disclosure of the
      underlying reaction mechanisms is challenging due to the rapid nature of these
      processes and the intricate identification of how many solvent molecules are
      involved. Here combining broadband femtosecond transient absorption and quantum
      mechanics/molecular mechanics simulations, we show for one of the most reactive
      species, diphenylcarbene, that the decision-maker is not the nearest solvent
      molecule but its neighbour. The hydrogen bonding dynamics determine which
      reaction channels are accessible in binary solvent mixtures at room temperature.
      In-depth analysis of the amount of nascent intermediates corroborates the
      importance of a hydrogen-bonded complex with a protic solvent molecule, in
      striking analogy to complexes found at cryogenic temperatures. Our results show
      that adjacent solvent molecules take the role of key abettors rather than
      bystanders for the fate of the reactive intermediate.

PMID- 27708265
TI  - Spatiotemporal control of cell-cell reversible interactions using molecular
      engineering.
AB  - Manipulation of cell-cell interactions has potential applications in basic
      research and cell-based therapy. Herein, using a combination of metabolic glycan
      labelling and bio-orthogonal click reaction, we engineer cell membranes with beta
      cyclodextrin and subsequently manipulate cell behaviours via photo-responsive
      host-guest recognition. With this methodology, we demonstrate reversible
      manipulation of cell assembly and disassembly. The method enables light
      controllable reversible assembly of cell-cell adhesion, in contrast with
      previously reported irreversible effects, in which altered structure could not be
      reused. We also illustrate the utility of the method by designing a cell-based
      therapy. Peripheral blood mononuclear cells modified with aptamer are effectively
      redirected towards target cells, resulting in enhanced cell apoptosis. Our
      approach allows precise control of reversible cell-cell interactions and we
      expect that it will promote further developments of cell-based therapy.

PMID- 27708266
TI  - Mechanism of pH-dependent activation of the sodium-proton antiporter NhaA.
AB  - Escherichia coli NhaA is a prototype sodium-proton antiporter, which has been
      extensively characterized by X-ray crystallography, biochemical and biophysical
      experiments. However, the identities of proton carriers and details of pH
      regulated mechanism remain controversial. Here we report constant pH molecular
      dynamics data, which reveal that NhaA activation involves a net charge switch of
      a pH sensor at the entrance of the cytoplasmic funnel and opening of a
      hydrophobic gate at the end of the funnel. The latter is triggered by charging of
      Asp164, the first proton carrier. The second proton carrier Lys300 forms a salt
      bridge with Asp163 in the inactive state, and releases a proton when a sodium ion
      binds Asp163. These data reconcile current models and illustrate the power of
      state-of-the-art molecular dynamics simulations in providing atomic details of
      proton-coupled transport across membrane which is challenging to elucidate by
      experimental techniques.

PMID- 27708268
TI  - A route for a strong increase of critical current in nanostrained iron-based
      superconductors.
AB  - The critical temperature Tc and the critical current density Jc determine the
      limits to large-scale superconductor applications. Superconductivity emerges at
      Tc. The practical current-carrying capability, measured by Jc, is the ability of
      defects in superconductors to pin the magnetic vortices, and that may reduce Tc.
      Simultaneous increase of Tc and Jc in superconductors is desirable but very
      difficult to realize. Here we demonstrate a route to raise both Tc and Jc
      together in iron-based superconductors. By using low-energy proton irradiation,
      we create cascade defects in FeSe0.5Te0.5 films. Tc is enhanced due to the
      nanoscale compressive strain and proximity effect, whereas Jc is doubled under
      zero field at 4.2 K through strong vortex pinning by the cascade defects and
      surrounding nanoscale strain. At 12 K and above 15 T, one order of magnitude of
      Jc enhancement is achieved in both parallel and perpendicular magnetic fields to
      the film surface.

PMID- 27708269
TI  - Tuning the catalytic CO hydrogenation to straight- and long-chain
      aldehydes/alcohols and olefins/paraffins.
AB  - The catalytic CO hydrogenation is one of the most versatile large-scale chemical
      syntheses leading to variable chemical feedstock. While traditionally mainly
      methanol and long-chain hydrocarbons are produced by CO hydrogenation, here we
      show that the same reaction can be tuned to produce long-chain n-aldehydes, 1
      alcohols and olefins, as well as n-paraffins over potassium-promoted CoMn
      catalysts. The sum selectivity of aldehydes and alcohols is usually >50 wt%
      whereof up to ~97% can be n-aldehydes. While the product slate contains ~60% n
      aldehydes at /pCO=0.5, a 65/35% slate of paraffins/alcohols is obtained at a
      ratio of 9. A linear Anderson-Schulz-Flory behaviour, independent of the /pCO
      ratio, is found for the sum of C4+ products. We advocate a synergistic
      interaction between a Mn5O8 oxide and a bulk Co2C phase, promoted by the presence
      of potassium, to be responsible for the unique product spectra in our studies.

PMID- 27708267
TI  - A high-quality human reference panel reveals the complexity and distribution of
      genomic structural variants.
AB  - Structural variation (SV) represents a major source of differences between
      individual human genomes and has been linked to disease phenotypes. However, the
      majority of studies provide neither a global view of the full spectrum of these
      variants nor integrate them into reference panels of genetic variation. Here, we
      analyse whole genome sequencing data of 769 individuals from 250 Dutch families,
      and provide a haplotype-resolved map of 1.9 million genome variants across 9
      different variant classes, including novel forms of complex indels, and
      retrotransposition-mediated insertions of mobile elements and processed RNAs. A
      large proportion are previously under reported variants sized between 21 and 100
      bp. We detect 4 megabases of novel sequence, encoding 11 new transcripts.
      Finally, we show 191 known, trait-associated SNPs to be in strong linkage
      disequilibrium with SVs and demonstrate that our panel facilitates accurate
      imputation of SVs in unrelated individuals.

PMID- 27708270
TI  - INPPL1 gene mutations in opsismodysplasia.
AB  - The INPPL1 (inositol polyphosphate phosphatase-like 1) gene encodes the inositol
      phosphatase, SHIP2 (for src homology 2 domain-containing inositol phosphatase 2).
      SHIP2 functions to dephosphorylate, and negatively regulate, the lipid second
      messenger phosphatidylinositol (3,4,5)P3. SHIP2 has been well studied in the area
      of insulin resistance and obesity but has roles in cancer and other disorders.
      Recently, it was reported that mutations in INPPL1 cause opsismodysplasia, a
      rare, autosomal recessive severe skeletal dysplasia. This review focuses on the
      mutations associated with opsismodysplasia and explores the role of INPPL1/ SHIP2
      in skeletal development.

PMID- 27708271
TI  - Most Martin-Bell syndrome (FMR1-related disorder) Venezuelan patients did not
      show CGG expansion but instead display genetic heterogeneity.
AB  - Martin-Bell syndrome is mainly caused by the expansion of CGG trinucleotide
      repeats (>200 CGG) in the first exon of the FMR1 gene, leading to
      hypermethylation of the promoter region and silencing of the FMR1 protein
      expression. These changes are responsible for a phenotype with varying degrees of
      mental retardation, a long face with large and protruding ears, macroorchidism
      and autistic behavior. There may also be, however, patients who exhibit typical
      features of the syndrome without any expansion in the FMR1 gene; thus, other
      mechanisms affecting the expression of the FMR1 gene were assessed in 25 out of
      29 ascertained patients with the typical phenotype without full mutation.
      Promoter methylation status of FMR1, mutations in its sequence and copy number
      variations (CNVs) in genes associated with intellectual disability were
      investigated. In 25 independent male patients without expansion, the promoter
      region was unmethylated; one patient with a full mutation showed methylation
      mosaicism; and a female patient had 81.2% of CpG sites methylated and 18.8%
      hemimethylated. One heterozygous duplication in exon 6 of the PDCD6 gene
      (programmed cell death 6) and a heterozygous deletion in exon 5 of the CHL1 gene
      (cell adhesion molecule L1), respectively, were found in two independent
      patients.

PMID- 27708272
TI  - Detection of SHOX gene aberrations in routine diagnostic practice and evaluation
      of phenotype scoring form effectiveness.
AB  - Heterozygous aberrations of SHOX gene have been reported to be responsible for
      Leri-Weill dyschondrosteosis (LWD) and small portion of idiopathic short stature.
      The study was established to assess effectiveness of using phenotype 'scoring
      form' in patients indicated for SHOX gene defect analysis. The submitted study is
      based on a retrospective group of 352 unrelated patients enrolled as a part of
      the routine diagnostic practice and analyzed for aberrations affecting the SHOX
      gene. All participants were scanned for deletion/duplication within the main
      pseudoautosomal region (PAR1) using the multiplex ligation-dependent probe
      amplification (MLPA) method. The phenotype 'scoring form' is used in our
      laboratory practice to preselect patients for subsequent mutation analysis of
      SHOX gene-coding sequences. The overall detection rate was 11.1% but there was a
      significant increase in frequency of SHOX gene defect positive with increasing
      achieved score (P<0.0001). The most frequent aberration was a causal deletion
      within PAR1. In three probands, MLPA analysis indicated a more complex
      rearrangement. Madelung deformity or co-occurrence of disproportionate short
      stature, short forearm and muscular hypertrophy had represented the most potent
      markers to determine the likelihood of SHOX gene defect detection. We conclude
      that appliance of phenotype 'scoring form' had saved excessive sample analysis
      and enabled effective routine diagnostic testing.

PMID- 27708274
TI  - Direct X-ray photoconversion in flexible organic thin film devices operated below
      1 V.
AB  - The application of organic electronic materials for the detection of ionizing
      radiations is very appealing thanks to their mechanical flexibility, low-cost and
      simple processing in comparison to their inorganic counterpart. In this work we
      investigate the direct X-ray photoconversion process in organic thin film
      photoconductors. The devices are realized by drop casting solution-processed bis
      (triisopropylsilylethynyl)pentacene (TIPS-pentacene) onto flexible plastic
      substrates patterned with metal electrodes; they exhibit a strong sensitivity to
      X-rays despite the low X-ray photon absorption typical of low-Z organic
      materials. We propose a model, based on the accumulation of photogenerated
      charges and photoconductive gain, able to describe the magnitude as well as the
      dynamics of the X-ray-induced photocurrent. This finding allows us to fabricate
      and test a flexible 2 * 2 pixelated X-ray detector operating at 0.2 V, with gain
      and sensitivity up to 4.7 * 104 and 77,000 nC mGy-1 cm-3, respectively.

PMID- 27708273
TI  - The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD
      in the United States.
AB  - The current study characterizes a cohort of limb-girdle muscular dystrophy (LGMD)
      in the United States using whole-exome sequencing. Fifty-five families affected
      by LGMD were recruited using an institutionally approved protocol. Exome
      sequencing was performed on probands and selected parental samples. Pathogenic
      mutations and cosegregation patterns were confirmed by Sanger sequencing. Twenty
      two families (40%) had novel and previously reported pathogenic mutations,
      primarily in LGMD genes, and also in genes for Duchenne muscular dystrophy,
      facioscapulohumeral muscular dystrophy, congenital myopathy, myofibrillar
      myopathy, inclusion body myopathy and Pompe disease. One family was diagnosed via
      clinical testing. Dominant mutations were identified in COL6A1, COL6A3, FLNC,
      LMNA, RYR1, SMCHD1 and VCP, recessive mutations in ANO5, CAPN3, GAA, LAMA2, SGCA
      and SGCG, and X-linked mutations in DMD. A previously reported variant in DMD was
      confirmed to be benign. Exome sequencing is a powerful diagnostic tool for LGMD.
      Despite careful phenotypic screening, pathogenic mutations were found in other
      muscle disease genes, largely accounting for the increased sensitivity of exome
      sequencing. Our experience suggests that broad sequencing panels are useful for
      these analyses because of the phenotypic overlap of many neuromuscular
      conditions. The confirmation of a benign DMD variant illustrates the potential of
      exome sequencing to help determine pathogenicity.

PMID- 27708275
TI  - A modular platform for one-step assembly of multi-component membrane systems by
      fusion of charged proteoliposomes.
AB  - An important goal in synthetic biology is the assembly of biomimetic cell-like
      structures, which combine multiple biological components in synthetic lipid
      vesicles. A key limiting assembly step is the incorporation of membrane proteins
      into the lipid bilayer of the vesicles. Here we present a simple method for
      delivery of membrane proteins into a lipid bilayer within 5 min. Fusogenic
      proteoliposomes, containing charged lipids and membrane proteins, fuse with
      oppositely charged bilayers, with no requirement for detergent or fusion
      promoting proteins, and deliver large, fragile membrane protein complexes into
      the target bilayers. We demonstrate the feasibility of our method by assembling a
      minimal electron transport chain capable of adenosine triphosphate (ATP)
      synthesis, combining Escherichia coli F1Fo ATP-synthase and the primary proton
      pump bo3-oxidase, into synthetic lipid vesicles with sizes ranging from 100 nm to
      ~10 MUm. This provides a platform for the combination of multiple sets of
      membrane protein complexes into cell-like artificial structures.

PMID- 27708277
TI  - Diabetes: Cardiovascular benefits of semaglutide.

PMID- 27708276
TI  - A distinct holoenzyme organization for two-subunit pyruvate carboxylase.
AB  - Pyruvate carboxylase (PC) has important roles in metabolism and is crucial for
      virulence for some pathogenic bacteria. PC contains biotin carboxylase (BC),
      carboxyltransferase (CT) and biotin carboxyl carrier protein (BCCP) components.
      It is a single-chain enzyme in eukaryotes and most bacteria, and functions as a
      500 kD homo-tetramer. In contrast, PC is a two-subunit enzyme in a collection of
      Gram-negative bacteria, with the alpha subunit containing the BC and the beta
      subunit the CT and BCCP domains, and it is believed that the holoenzyme has
      alpha4beta4 stoichiometry. We report here the crystal structures of a two-subunit
      PC from Methylobacillus flagellatus. Surprisingly, our structures reveal an
      alpha2beta4 stoichiometry, and the overall architecture of the holoenzyme is
      strikingly different from that of the homo-tetrameric PCs. Biochemical and
      mutagenesis studies confirm the stoichiometry and other structural observations.
      Our functional studies in Pseudomonas aeruginosa show that its two-subunit PC is
      important for colony morphogenesis.

PMID- 27708279
TI  - Hypertension: Lower or higher blood-pressure targets for high-risk patients?

PMID- 27708280
TI  - Antiplatelet therapy: What have we learned from the ANTARCTIC trial?

PMID- 27708278
TI  - Neurohormonal activation in heart failure with reduced ejection fraction.
AB  - Heart failure with reduced ejection fraction (HFrEF) develops when cardiac output
      falls as a result of cardiac injury. The most well-recognized of the compensatory
      homeostatic responses to a fall in cardiac output are activation of the
      sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS).
      In the short term, these 'neurohormonal' systems induce a number of changes in
      the heart, kidneys, and vasculature that are designed to maintain cardiovascular
      homeostasis. However, with chronic activation, these responses result in
      haemodynamic stress and exert deleterious effects on the heart and the
      circulation. Neurohormonal activation is now known to be one of the most
      important mechanisms underlying the progression of heart failure, and therapeutic
      antagonism of neurohormonal systems has become the cornerstone of contemporary
      pharmacotherapy for heart failure. In this Review, we discuss the effects of
      neurohormonal activation in HFrEF and highlight the mechanisms by which these
      systems contribute to disease progression.

PMID- 27708282
TI  - Sensing the quantum limit in scanning tunnelling spectroscopy.
AB  - The tunnelling current in scanning tunnelling spectroscopy (STS) is typically and
      often implicitly modelled by a continuous and homogeneous charge flow. If the
      charging energy of a single-charge quantum sufficiently exceeds the thermal
      energy, however, the granularity of the current becomes non-negligible. In this
      quantum limit, the capacitance of the tunnel junction mediates an interaction of
      the tunnelling electrons with the surrounding electromagnetic environment and
      becomes a source of noise itself, which cannot be neglected in STS. Using a
      scanning tunnelling microscope operating at 15 mK, we show that we operate in
      this quantum limit, which determines the ultimate energy resolution in STS. The
      P(E)-theory describes the probability for a tunnelling electron to exchange
      energy with the environment and can be regarded as the energy resolution
      function. We experimentally demonstrate this effect with a superconducting
      aluminium tip and a superconducting aluminium sample, where it is most
      pronounced.

PMID- 27708281
TI  - The fractal heart - embracing mathematics in the cardiology clinic.
AB  - For clinicians grappling with quantifying the complex spatial and temporal
      patterns of cardiac structure and function (such as myocardial trabeculae,
      coronary microvascular anatomy, tissue perfusion, myocyte histology, electrical
      conduction, heart rate, and blood-pressure variability), fractal analysis is a
      powerful, but still underused, mathematical tool. In this Perspectives article,
      we explain some fundamental principles of fractal geometry and place it in a
      familiar medical setting. We summarize studies in the cardiovascular sciences in
      which fractal methods have successfully been used to investigate disease
      mechanisms, and suggest potential future clinical roles in cardiac imaging and
      time series measurements. We believe that clinical researchers can deploy
      innovative fractal solutions to common cardiac problems that might ultimately
      translate into advancements for patient care.

PMID- 27708284
TI  - Blood pressure differences between office and home settings among Japanese
      normotensive subjects and hypertensive patients.
AB  - This study attempted to clarify the differences in blood pressure (BP) between
      the office (clinic) and home settings in patients with controlled, sustained,
      masked or white-coat hypertension. The following formula was used: office mean
      systolic BP (omSBP)-mean morning home SBP (mmhSBP)/office mean diastolic BP
      (omDBP)-mean morning home DBP (mmhDBP). The paired t-test was used for
      statistical analysis. The omSBP-mmhSBP/omDBP-mmhDBP calculation yielded the
      following results: among normotensive subjects, -1.1+/-11.2/-1.7+/-8.5 mm Hg
      (mean SBP and mean DBP were higher at home than in the office; n=451, P=0.038 in
      SBP, P=0.000 in DBP); in controlled hypertensive patients, -0.42+/-10.9/-2.2+/
      8.2 mm Hg (n=1362, P=0.160 in SBP, P=0.000 in DBP); among sustained hypertensive
      patients, 5.6+/-14.7/0.048+/-9.9 mm Hg (n=1370, P=0.000 in SBP, P=0.857 in DBP);
      in masked hypertensive patients, -15.3+/-12.9/-9.3+/-9.5 mm Hg (n=1308, both
      P=0.000); and among white-coat hypertensive patients, 23.7+/-13.2/8.2+/-9.1 mm Hg
      (n=580, both P=0.000). Our results showed a difference of 5 mm Hg in SBP among
      sustained hypertensive patients, as recommended by the Japanese Society of
      Hypertension Guidelines for the Management of Hypertension; however, in other
      hypertensive patient types, the differences in SBP and DBP between office and
      home measurements differed by >5 mm Hg. Office and home BP measurements should be
      interpreted cautiously, keeping in mind the clinical setting.

PMID- 27708283
TI  - Obesity-associated NLRC4 inflammasome activation drives breast cancer
      progression.
AB  - Obesity is associated with an increased risk of developing breast cancer and is
      also associated with worse clinical prognosis. The mechanistic link between
      obesity and breast cancer progression remains unclear, and there has been no
      development of specific treatments to improve the outcome of obese cancer
      patients. Here we show that obesity-associated NLRC4 inflammasome activation/
      interleukin (IL)-1 signalling promotes breast cancer progression. The tumour
      microenvironment in the context of obesity induces an increase in tumour
      infiltrating myeloid cells with an activated NLRC4 inflammasome that in turn
      activates IL-1beta, which drives disease progression through adipocyte-mediated
      vascular endothelial growth factor A (VEGFA) expression and angiogenesis. Further
      studies show that treatment of mice with metformin inhibits obesity-associated
      tumour progression associated with a marked decrease in angiogenesis. This report
      provides a causal mechanism by which obesity promotes breast cancer progression
      and lays out a foundation to block NLRC4 inflammasome activation or IL-1beta
      signalling transduction that may be useful for the treatment of obese cancer
      patients.

PMID- 27708289
TI  - Monitoring: safeguarding the world's largest lake.

PMID- 27708287
TI  - Pollution: centralized pilot for e-waste processing.

PMID- 27708286
TI  - Spontaneous assembly of chemically encoded two-dimensional coacervate droplet
      arrays by acoustic wave patterning.
AB  - The spontaneous assembly of chemically encoded, molecularly crowded, water-rich
      micro-droplets into periodic defect-free two-dimensional arrays is achieved in
      aqueous media by a combination of an acoustic standing wave pressure field and in
      situ complex coacervation. Acoustically mediated coalescence of primary droplets
      generates single-droplet per node micro-arrays that exhibit variable surface
      attachment properties, spontaneously uptake dyes, enzymes and particles, and
      display spatial and time-dependent fluorescence outputs when exposed to a
      reactant diffusion gradient. In addition, coacervate droplet arrays exhibiting
      dynamical behaviour and exchange of matter are prepared by inhibiting coalescence
      to produce acoustically trapped lattices of droplet clusters that display fast
      and reversible changes in shape and spatial configuration in direct response to
      modulations in the acoustic frequencies and fields. Our results offer a novel
      route to the design and construction of 'water-in-water' micro-droplet arrays
      with controllable spatial organization, programmable signalling pathways and
      higher order collective behaviour.

PMID- 27708285
TI  - Evolutionary trajectories of snake genes and genomes revealed by comparative
      analyses of five-pacer viper.
AB  - Snakes have numerous features distinctive from other tetrapods and a rich history
      of genome evolution that is still obscure. Here, we report the high-quality
      genome of the five-pacer viper, Deinagkistrodon acutus, and comparative analyses
      with other representative snake and lizard genomes. We map the evolutionary
      trajectories of transposable elements (TEs), developmental genes and sex
      chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific
      expansion, and many viper TEs show brain-specific gene expression along with
      their nearby genes. We detect signatures of adaptive evolution in olfactory,
      venom and thermal-sensing genes and also functional degeneration of genes
      associated with vision and hearing. Lineage-specific relaxation of functional
      constraints on respective Hox and Tbx limb-patterning genes supports fossil
      evidence for a successive loss of forelimbs then hindlimbs during snake
      evolution. Finally, we infer that the ZW sex chromosome pair had undergone at
      least three recombination suppression events in the ancestor of advanced snakes.
      These results altogether forge a framework for our deep understanding into
      snakes' history of molecular evolution.

PMID- 27708290
TI  - Cardiovascular biology: 'Good' fat may cut heart disease.

PMID- 27708291
TI  - Upward revision of global fossil fuel methane emissions based on isotope
      database.
AB  - Methane has the second-largest global radiative forcing impact of anthropogenic
      greenhouse gases after carbon dioxide, but our understanding of the global
      atmospheric methane budget is incomplete. The global fossil fuel industry
      (production and usage of natural gas, oil and coal) is thought to contribute 15
      to 22 per cent of methane emissions to the total atmospheric methane budget.
      However, questions remain regarding methane emission trends as a result of fossil
      fuel industrial activity and the contribution to total methane emissions of
      sources from the fossil fuel industry and from natural geological seepage, which
      are often co-located. Here we re-evaluate the global methane budget and the
      contribution of the fossil fuel industry to methane emissions based on long-term
      global methane and methane carbon isotope records. We compile the largest
      isotopic methane source signature database so far, including fossil fuel,
      microbial and biomass-burning methane emission sources. We find that total fossil
      fuel methane emissions (fossil fuel industry plus natural geological seepage) are
      not increasing over time, but are 60 to 110 per cent greater than current
      estimates owing to large revisions in isotope source signatures. We show that
      this is consistent with the observed global latitudinal methane gradient. After
      accounting for natural geological methane seepage, we find that methane emissions
      from natural gas, oil and coal production and their usage are 20 to 60 per cent
      greater than inventories. Our findings imply a greater potential for the fossil
      fuel industry to mitigate anthropogenic climate forcing, but we also find that
      methane emissions from natural gas as a fraction of production have declined from
      approximately 8 per cent to approximately 2 per cent over the past three decades.

PMID- 27708292
TI  - Materials: Graphene oxide is stiff yet bendy.

PMID- 27708293
TI  - Open data: policies need policing.

PMID- 27708295
TI  - Snakebites: costing recombinant antivenoms.

PMID- 27708296
TI  - Astronomy: Magnetism drives star birth.

PMID- 27708297
TI  - Cancer immunotherapy: Dual action of targeted T cells.

PMID- 27708299
TI  - Open data: curation is under-resourced.

PMID- 27708302
TI  - Biomaterials: 'Bones' made with 3D printer.

PMID- 27708300
TI  - Donald Ainslie Henderson (1928-2016).

PMID- 27708304
TI  - Biogeochemistry: Rebalancing the global methane budget.

PMID- 27708306
TI  - Microbiology: Toad probiotic fights fungus.

PMID- 27708303
TI  - Cobalt carbide nanoprisms for direct production of lower olefins from syngas.
AB  - Lower olefins-generally referring to ethylene, propylene and butylene-are basic
      carbon-based building blocks that are widely used in the chemical industry, and
      are traditionally produced through thermal or catalytic cracking of a range of
      hydrocarbon feedstocks, such as naphtha, gas oil, condensates and light alkanes.
      With the rapid depletion of the limited petroleum reserves that serve as the
      source of these hydrocarbons, there is an urgent need for processes that can
      produce lower olefins from alternative feedstocks. The 'Fischer-Tropsch to
      olefins' (FTO) process has long offered a way of producing lower olefins directly
      from syngas-a mixture of hydrogen and carbon monoxide that is readily derived
      from coal, biomass and natural gas. But the hydrocarbons obtained with the FTO
      process typically follow the so-called Anderson-Schulz-Flory distribution, which
      is characterized by a maximum C2-C4 hydrocarbon fraction of about 56.7 per cent
      and an undesired methane fraction of about 29.2 per cent (refs 1, 10, 11, 12).
      Here we show that, under mild reaction conditions, cobalt carbide quadrangular
      nanoprisms catalyse the FTO conversion of syngas with high selectivity for the
      production of lower olefins (constituting around 60.8 per cent of the carbon
      products), while generating little methane (about 5.0 per cent), with the ratio
      of desired unsaturated hydrocarbons to less valuable saturated hydrocarbons
      amongst the C2-C4 products being as high as 30. Detailed catalyst
      characterization during the initial reaction stage and theoretical calculations
      indicate that preferentially exposed {101} and {020} facets play a pivotal role
      during syngas conversion, in that they favour olefin production and inhibit
      methane formation, and thereby render cobalt carbide nanoprisms a promising new
      catalyst system for directly converting syngas into lower olefins.

PMID- 27708305
TI  - Materials: Shape-shifting gel blooms.

PMID- 27708311
TI  - Conservation: Restored forests ignore history.

PMID- 27708313
TI  - Catalysis: Cobalt gets in shape.

PMID- 27708314
TI  - Astronomy: How black hole obscures itself.

PMID- 27708315
TI  - Neuroscience: Hunger overrides other motivations.

PMID- 27708309
TI  - Circuit-based interrogation of sleep control.
AB  - Sleep is a fundamental biological process observed widely in the animal kingdom,
      but the neural circuits generating sleep remain poorly understood. Understanding
      the brain mechanisms controlling sleep requires the identification of key neurons
      in the control circuits and mapping of their synaptic connections. Technical
      innovations over the past decade have greatly facilitated dissection of the sleep
      circuits. This has set the stage for understanding how a variety of environmental
      and physiological factors influence sleep. The ability to initiate and terminate
      sleep on command will also help us to elucidate its functions within and beyond
      the brain.

PMID- 27708316
TI  - Corporate culture has no place in academia.

PMID- 27708317
TI  - Syrian seed bank gets new home away from war.

PMID- 27708318
TI  - Clean up energy innovation.

PMID- 27708319
TI  - US left with just one working fusion reactor - for now.

PMID- 27708320
TI  - The limits to human lifespan must be respected.

PMID- 27708321
TI  - UK bioethicists eye designer babies and CRISPR cows.

PMID- 27708323
TI  - Correction.

PMID- 27708322
TI  - Premature burial, show business and the Nobel prize.

PMID- 27708324
TI  - A Mars rocket, an artificial pancreas and a plutonium problem.

PMID- 27708325
TI  - Renewables need a grand-challenge strategy.

PMID- 27708326
TI  - Medicine Nobel for research on how cells 'eat themselves'.

PMID- 27708327
TI  - Democratic databases: science on GitHub.

PMID- 27708328
TI  - Oppose the UK Higher Education and Research Bill.

PMID- 27708329
TI  - Can we open the black box of AI?

PMID- 27708330
TI  - Warning to forest destroyers: this scientist will catch you.

PMID- 27708331
TI  - Physics of 2D exotic matter wins Nobel.

PMID- 27708332
TI  - Mission accomplished: Rosetta crashes into comet.

PMID- 27708333
TI  - Differential hepatic distribution of insulin receptor substrates causes selective
      insulin resistance in diabetes and obesity.
AB  - Hepatic insulin signalling involves insulin receptor substrates (Irs) 1/2, and is
      normally associated with the inhibition of gluconeogenesis and activation of
      lipogenesis. In diabetes and obesity, insulin no longer suppresses hepatic
      gluconeogenesis, while continuing to activate lipogenesis, a state referred to as
      'selective insulin resistance'. Here, we show that 'selective insulin resistance'
      is caused by the differential expression of Irs1 and Irs2 in different zones of
      the liver. We demonstrate that hepatic Irs2-knockout mice develop 'selective
      insulin resistance', whereas mice lacking in Irs1, or both Irs1 and Irs2, develop
      'total insulin resistance'. In obese diabetic mice, Irs1/2-mediated insulin
      signalling is impaired in the periportal zone, which is the primary site of
      gluconeogenesis, but enhanced in the perivenous zone, which is the primary site
      of lipogenesis. While hyperinsulinaemia reduces Irs2 expression in both the
      periportal and perivenous zones, Irs1 expression, which is predominantly in the
      perivenous zone, remains mostly unaffected. These data suggest that 'selective
      insulin resistance' is induced by the differential distribution, and alterations
      of hepatic Irs1 and Irs2 expression.

PMID- 27708334
TI  - Loss of immune tolerance to IL-2 in type 1 diabetes.
AB  - Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune
      attack against pancreas-specific antigens, effecting the destruction of insulin
      producing beta-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic
      autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific
      for a single orthologous epitope of IL-2, are present in the peripheral blood of
      non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation
      of anti-IL-2 autoantibodies is genetically determined and their titre increases
      with age and disease onset. In T1D patients, circulating IgG memory B cells
      specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2
      autoantibodies cloned from T1D patients demonstrate clonality, a high degree of
      somatic hypermutation and nanomolar affinities, indicating a germinal centre
      origin and underscoring the synergy between cognate autoreactive T and B cells
      leading to defective immune tolerance.

PMID- 27708336
TI  - Metal-free photochemical silylations and transfer hydrogenations of benzenoid
      hydrocarbons and graphene.
AB  - The first hydrogenation step of benzene, which is endergonic in the electronic
      ground state (S0), becomes exergonic in the first triplet state (T1). This is in
      line with Baird's rule, which tells that benzene is antiaromatic and destabilized
      in its T1 state and also in its first singlet excited state (S1), opposite to S0,
      where it is aromatic and remarkably unreactive. Here we utilized this feature to
      show that benzene and several polycyclic aromatic hydrocarbons (PAHs) to various
      extents undergo metal-free photochemical (hydro)silylations and transfer
      hydrogenations at mild conditions, with the highest yield for naphthalene
      (photosilylation: 21%). Quantum chemical computations reveal that T1-state
      benzene is excellent at H-atom abstraction, while cyclooctatetraene, aromatic in
      the T1 and S1 states according to Baird's rule, is unreactive. Remarkably, also
      CVD-graphene on SiO2 is efficiently transfer-photohydrogenated using formic
      acid/water mixtures together with white light or solar irradiation under metal
      free conditions.

PMID- 27708337
TI  - Sorting cells by their dynamical properties.
AB  - Recent advances in cell sorting aim at the development of novel methods that are
      sensitive to various mechanical properties of cells. Microfluidic technologies
      have a great potential for cell sorting; however, the design of many micro
      devices is based on theories developed for rigid spherical particles with size as
      a separation parameter. Clearly, most bioparticles are non-spherical and
      deformable and therefore exhibit a much more intricate behavior in fluid flow
      than rigid spheres. Here, we demonstrate the use of cells' mechanical and
      dynamical properties as biomarkers for separation by employing a combination of
      mesoscale hydrodynamic simulations and microfluidic experiments. The dynamic
      behavior of red blood cells (RBCs) within deterministic lateral displacement
      (DLD) devices is investigated for different device geometries and viscosity
      contrasts between the intra-cellular fluid and suspending medium. We find that
      the viscosity contrast and associated cell dynamics clearly determine the RBC
      trajectory through a DLD device. Simulation results compare well to experiments
      and provide new insights into the physical mechanisms which govern the sorting of
      non-spherical and deformable cells in DLD devices. Finally, we discuss the
      implications of cell dynamics for sorting schemes based on properties other than
      cell size, such as mechanics and morphology.

PMID- 27708339
TI  - Corrigendum: Epigenetic inactivation of the CpG demethylase TET1 as a DNA
      methylation feedback loop in human cancers.

PMID- 27708338
TI  - Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha
      Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans.
AB  - Misfolded alpha-synuclein (AS) and other neurodegenerative disorder proteins
      display prion-like transmission of protein aggregation. Factors responsible for
      the initiation of AS aggregation are unknown. To evaluate the role of amyloid
      proteins made by the microbiota we exposed aged rats and transgenic C. elegans to
      E. coli producing the extracellular bacterial amyloid protein curli. Rats exposed
      to curli-producing bacteria displayed increased neuronal AS deposition in both
      gut and brain and enhanced microgliosis and astrogliosis compared to rats exposed
      to either mutant bacteria unable to synthesize curli, or to vehicle alone.
      Animals exposed to curli producing bacteria also had more expression of TLR2, IL
      6 and TNF in the brain than the other two groups. There were no differences among
      the rat groups in survival, body weight, inflammation in the mouth, retina,
      kidneys or gut epithelia, and circulating cytokine levels. AS-expressing C.
      elegans fed on curli-producing bacteria also had enhanced AS aggregation. These
      results suggest that bacterial amyloid functions as a trigger to initiate AS
      aggregation through cross-seeding and also primes responses of the innate immune
      system.

PMID- 27708341
TI  - Nano-inspired fluidic interactivity for boiling heat transfer: impact and
      criteria.
AB  - The enhancement of boiling heat transfer, the most powerful energy-transferring
      technology, will lead to milestones in the development of high-efficiency, next
      generation energy systems. Perceiving nano-inspired interface functionalities
      from their rough morphologies, we demonstrate interface-induced liquid refreshing
      is essential to improve heat transfer by intrinsically avoiding Leidenfrost
      phenomenon. High liquid accessibility of hemi-wicking and catalytic nucleation,
      triggered by the morphological and hydrodynamic peculiarities of nano-inspired
      interfaces, contribute to the critical heat flux (CHF) and the heat transfer
      coefficient (HTC). Our experiments show CHF is a function of universal
      hydrodynamic characteristics involving interfacial liquid accessibility and HTC
      is improved with a higher probability of smaller nuclei with less superheat.
      Considering the interface-induced and bulk liquid accessibility at boiling, we
      discuss functionalizing the interactivity between an interface and a
      counteracting fluid seeking to create a novel interface, a so-called smart
      interface, for a breakthrough in boiling and its pragmatic application in energy
      systems.

PMID- 27708340
TI  - Activation and increase of radio-sensitive CD11b+ recruited Kupffer
      cells/macrophages in diet-induced steatohepatitis in FGF5 deficient mice.
AB  - We have recently reported that Kupffer cells consist of two subsets, radio
      resistant resident CD68+ Kupffer cells and radio-sensitive recruited CD11b+
      Kupffer cells/macrophages (Mphis). Non-alcoholic steatohepatitis (NASH) is
      characterized not only by hepatic steatosis but also chronic inflammation and
      fibrosis. In the present study, we investigated the immunological mechanism of
      diet-induced steatohepatitis in fibroblast growth factor 5 (FGF5) deficient mice.
      After consumption of a high fat diet (HFD) for 8 weeks, FGF5 null mice developed
      severe steatohepatitis and fibrosis resembling human NASH. F4/80+ Mphis which
      were both CD11b and CD68 positive accumulated in the liver. The production of TNF
      and FasL indicated that they are the pivotal effectors in this hepatitis. The
      weak phagocytic activity and lack of CRIg mRNA suggested that they were recruited
      Mphis. Intermittent exposure to 1 Gy irradiation markedly decreased these Mphis
      and dramatically inhibited liver inflammation without attenuating steatosis.
      However, depletion of the resident subset by clodronate liposome (c-lipo)
      treatment increased the Mphis and tended to exacerbate disease progression.
      Recruited CD11b+ CD68+ Kupffer cells/Mphis may play an essential role in
      steatohepatitis and fibrosis in FGF5 null mice fed with a HFD. Recruitment and
      activation of bone marrow derived Mphis is the key factor to develop
      steatohepatitis from simple steatosis.

PMID- 27708342
TI  - Nonlinear backbone torsional pair correlations in proteins.
AB  - Protein allostery requires dynamical structural correlations. Physical origin of
      which, however, remain elusive despite intensive studies during last two and half
      decades. Based on analysis of molecular dynamics (MD) simulation trajectories for
      ten proteins with different sizes and folds, we found that nonlinear backbone
      torsional pair (BTP) correlations, which are mainly spatially long-ranged and are
      dominantly executed by loop residues, exist extensively in most analyzed
      proteins. Examination of torsional motion for correlated BTPs suggested that such
      nonlinear correlations are mainly associated aharmonic torsional state
      transitions and in some cases strongly anisotropic local torsional motion of
      participating torsions, and occur on widely different and relatively longer time
      scales. In contrast, correlations between backbone torsions in stable alpha
      helices and beta strands are mainly linear and spatially short-ranged, and are
      more likely to associate with harmonic local torsional motion. Further analysis
      revealed that the direct cause of nonlinear contributions are heterogeneous
      linear correlations. These findings implicate a general search strategy for novel
      allosteric modulation sites of protein activities.

PMID- 27708343
TI  - Biodiversity loss and turnover in alternative states in the Mediterranean Sea: a
      case study on meiofauna.
AB  - In the Mediterranean Sea hard-bottom macroalgal meadows may switch to alternative
      and less-productive barrens grounds, as a result of sea urchins overgrazing.
      Meiofauna (and especially nematodes) represent key components of benthic
      ecosystems, are highly-diversified, sensitive to environmental change and
      anthropogenic impacts, but, so-far, have been neglected in studies on regime
      shifts. We report here that sedimentary organic matter contents, meiofaunal taxa
      richness and community composition, nematode alpha- and beta-biodiversity vary
      significantly between alternative macroalgal and barren states. The observed
      differences are consistent in six areas spread across the Mediterranean Sea,
      irrespective of barren extent. Our results suggest also that the low biodiversity
      levels in barren states are the result of habitat loss/fragmentation, which is
      associated also with a lower availability of trophic resources. Furthermore,
      differences in meiofaunal and nematode abundance, biomass and diversity between
      macroalgal meadow and barren states persist when the latter is not fully formed,
      or consists of patches interspersed in macroalgal meadows. Since barren grounds
      are expanding rapidly along the Mediterranean Sea and meiofauna are a key trophic
      component in marine ecosystems, we suggest that the extension and persistence of
      barrens at the expenses of macroalgal meadows could also affect resilience of
      higher trophic level.

PMID- 27708344
TI  - Illusions of having small or large invisible bodies influence visual perception
      of object size.
AB  - The size of our body influences the perceived size of the world so that objects
      appear larger to children than to adults. The mechanisms underlying this effect
      remain unclear. It has been difficult to dissociate visual rescaling of the
      external environment based on an individual's visible body from visual rescaling
      based on a central multisensory body representation. To differentiate these
      potential causal mechanisms, we manipulated body representation without a visible
      body by taking advantage of recent developments in body representation research.
      Participants experienced the illusion of having a small or large invisible body
      while object-size perception was tested. Our findings show that the perceived
      size of test-objects was determined by the size of the invisible body (inverse
      relation), and by the strength of the invisible body illusion. These findings
      demonstrate how central body representation directly influences visual size
      perception, without the need for a visible body, by rescaling the spatial
      representation of the environment.

PMID- 27708345
TI  - Characterization of maize roothairless6 which encodes a D-type cellulose synthase
      and controls the switch from bulge formation to tip growth.
AB  - Root hairs are tubular extensions of the epidermis. Root hairs of the monogenic
      recessive maize mutant roothairless 6 (rth6) are arrested after bulge formation
      during the transition to tip growth and display a rough cell surface. BSR-Seq in
      combination with Seq-walking and subsequent analyses of four independently
      generated mutant alleles established that rth6 encodes CSLD5 a plasma membrane
      localized 129 kD D-type cellulose synthase with eight transmembrane domains.
      Cellulose synthases are required for the biosynthesis of cellulose, the most
      abundant biopolymer of plant cell walls. Phylogenetic analyses revealed that RTH6
      is part of a monocot specific clade of D-type cellulose synthases. D-type
      cellulose synthases are highly conserved in the plant kingdom with five gene
      family members in maize and homologs even among early land plants such as the
      moss Physcomitrella patens or the clubmoss Selaginella moellendorffii. Expression
      profiling demonstrated that rth6 transcripts are highly enriched in root hairs as
      compared to all other root tissues. Moreover, in addition to the strong knock
      down of rth6 expression in young primary roots of the mutant rth6, the gene is
      also significantly down-regulated in rth3 and rth5 mutants, while it is up
      regulated in rth2 mutants, suggesting that these genes interact in cell wall
      biosynthesis.

PMID- 27708346
TI  - Role of areca nut induced JNK/ATF2/Jun axis in the activation of TGF-beta pathway
      in precancerous Oral Submucous Fibrosis.
AB  - Oral submucous fibrosis (OSF) is potentially premalignant with progressive and
      irreversible extracellular matrix deposition accompanied by epithelial atrophy
      and like other fibrotic disorders, is primarily a TGF-beta driven disease. OSF is
      caused by prolonged chewing of areca nut. Our previous studies reported a pivotal
      role for TGF-beta activation and its effects contributing to OSF. However, the
      mechanism for activation of TGF-beta signaling in OSF is still unknown. In this
      study we demonstrate activation of TGF-beta signaling with sub-cytotoxic dose of
      areca nut in epithelial cells and discovered a key role for pJNK in this process.
      In good correlation; pJNK was detected in OSF tissues but not in normal tissues.
      Moreover, activation of JNK was found to be dependent on muscarinic acid receptor
      induced Ca2+/CAMKII as well as ROS. JNK dependent phosphorylation of ATF2/c-Jun
      transcription factors resulted in TGF-beta transcription and its signaling.
      pATF2/p-c-Jun were enriched on TGF-beta promoter and co-localized in nuclei of
      epithelial cells upon areca nut treatment. In corroboration, OSF tissue sections
      also had nuclear pATF2 and p-c-Jun. Our results provide comprehensive mechanistic
      details of TGF-beta signaling induced by etiological agent areca nut in the
      manifestation of fibrosis which can lead to new therapeutic modalities for OSF.

PMID- 27708347
TI  - Humic acid inhibits HBV-induced autophagosome formation and induces apoptosis in
      HBV-transfected Hep G2 cells.
AB  - Hepatitis B Virus (HBV) utilizes several mechanisms to survive in the host cells
      and one of the main pathways being autophagosome formation. Humic acid (HA), one
      of the major components of Mineral pitch, is an Ayurvedic medicinal food,
      commonly used by the people of the Himalayan regions of Nepal and India for
      various body ailments. We hypothesized that HA could induce cell death and
      inhibit HBV-induced autophagy in hepatic cells. Incubation of Hep G2.2.1.5 cells
      (HepG2 cells stably expressing HBV) with HA (100 MUM) inhibited both cell
      proliferation and autophagosome formation significantly, while apoptosis
      induction was enhanced. Western blot results showed that HA incubation resulted
      in decreased levels of beclin-1, SIRT-1 and c-myc, while caspase-3 and beta
      catenin expression were up-regulated. Western blot results showed that HA
      significantly inhibited the expression of HBx (3-fold with 50 MUM and 5-fold with
      100 MUM) compared to control cells. When HA was incubated with HBx-transfected
      Hep G2 cells, HBx-induced autophagosome formation and beclin-1 levels were
      decreased. These data showed that HA induced apoptosis and inhibited HBV-induced
      autophagosome formation and proliferation in hepatoma cells.

PMID- 27708348
TI  - A chimeric protein-based malaria vaccine candidate induces robust T cell
      responses against Plasmodium vivax MSP119.
AB  - The most widespread Plasmodium species, Plasmodium vivax, poses a significant
      public health threat. An effective vaccine is needed to reduce global malaria
      burden. Of the erythrocytic stage vaccine candidates, the 19 kDa fragment of the
      P. vivax Merozoite Surface Protein 1 (PvMSP119) is one of the most promising. Our
      group has previously defined several promiscuous T helper epitopes within the
      PvMSP1 protein, with features that allow them to bind multiple MHC class II
      alleles. We describe here a P. vivax recombinant modular chimera based on MSP1
      (PvRMC-MSP1) that includes defined T cell epitopes genetically fused to PvMSP119.
      This vaccine candidate preserved structural elements of the native PvMSP119 and
      elicited cytophilic antibody responses, and CD4+ and CD8+ T cells capable of
      recognizing PvMSP119. Although CD8+ T cells that recognize blood stage antigens
      have been reported to control blood infection, CD8+ T cell responses induced by
      P. falciparum or P. vivax vaccine candidates based on MSP119 have not been
      reported. To our knowledge, this is the first time a protein based subunit
      vaccine has been able to induce CD8+ T cell against PvMSP119. The PvRMC-MSP1
      protein was also recognized by naturally acquired antibodies from individuals
      living in malaria endemic areas with an antibody profile associated with
      protection from infection. These features make PvRMC-MSP1 a promising vaccine
      candidate.

PMID- 27708351
TI  - Spatial and Structural Metrics for Living Cells Inspired by Statistical
      Mechanics.
AB  - Experimental observations in cell biology have advanced to a stage where theory
      could play a larger role, much as it has done in the physical sciences. Possibly
      the lack of a common framework within which experimentalists, computational
      scientists and theorists could equally contribute has hindered this development,
      for the worse of both disciplines. Here we demonstrate the usage of tools and
      concepts from statistical mechanics to describe processes inside living cells
      based on experimental data, suggesting that future theoretical/computational
      models may be based on such concepts. To illustrate the ideas, we describe the
      organisation of subcellular structures within the cell in terms of (density) pair
      correlation functions, and subsequently use the same concepts to follow nano
      sized objects being transported inside the cell. Finally, we quantify an
      interesting subcellular re-organisation, not previously discerned by molecular
      biology methods.

PMID- 27708350
TI  - Beatquency domain and machine learning improve prediction of cardiovascular death
      after acute coronary syndrome.
AB  - Frequency domain measures of heart rate variability (HRV) are associated with
      adverse events after a myocardial infarction. However, patterns in the
      traditional frequency domain (measured in Hz, or cycles per second) may capture
      different cardiac phenomena at different heart rates. An alternative is to
      consider frequency with respect to heartbeats, or beatquency. We compared the use
      of frequency and beatquency domains to predict patient risk after an acute
      coronary syndrome. We then determined whether machine learning could further
      improve the predictive performance. We first evaluated the use of pre-defined
      frequency and beatquency bands in a clinical trial dataset (N = 2302) for the HRV
      risk measure LF/HF (the ratio of low frequency to high frequency power). Relative
      to frequency, beatquency improved the ability of LF/HF to predict cardiovascular
      death within one year (Area Under the Curve, or AUC, of 0.730 vs. 0.704, p <
      0.001). Next, we used machine learning to learn frequency and beatquency bands
      with optimal predictive power, which further improved the AUC for beatquency to
      0.753 (p < 0.001), but not for frequency. Results in additional validation
      datasets (N = 2255 and N = 765) were similar. Our results suggest that beatquency
      and machine learning provide valuable tools in physiological studies of HRV.

PMID- 27708349
TI  - Improved Cryopreservation of Human Umbilical Vein Endothelial Cells: A Systematic
      Approach.
AB  - Cryopreservation of human umbilical vein endothelial cells (HUVECs) facilitated
      their commercial availability for use in vascular biology, tissue engineering and
      drug delivery research; however, the key variables in HUVEC cryopreservation have
      not been comprehensively studied. HUVECs are typically cryopreserved by cooling
      at 1  degrees C/min in the presence of 10% dimethyl sulfoxide (DMSO). We applied
      interrupted slow cooling (graded freezing) and interrupted rapid cooling with a
      hold time (two-step freezing) to identify where in the cooling process cryoinjury
      to HUVECs occurs. We found that linear cooling at 1  degrees C/min resulted in
      higher membrane integrities than linear cooling at 0.2  degrees C/min or
      nonlinear two-step freezing. DMSO addition procedures and compositions were also
      investigated. By combining hydroxyethyl starch with DMSO, HUVEC viability after
      cryopreservation was improved compared to measured viabilities of commercially
      available cryopreserved HUVECs and viabilities for HUVEC cryopreservation studies
      reported in the literature. Furthermore, HUVECs cryopreserved using our improved
      procedure showed high tube forming capability in a post-thaw angiogenesis assay,
      a standard indicator of endothelial cell function. As well as presenting superior
      cryopreservation procedures for HUVECs, the methods developed here can serve as a
      model to optimize the cryopreservation of other cells.

PMID- 27708352
TI  - Mechanism and comparison of needle-type non-thermal direct and indirect
      atmospheric pressure plasma jets on the degradation of dyes.
AB  - Purified water supply for human use, agriculture and industry is the major global
      priority nowadays. The advanced oxidation process based on atmospheric pressure
      non-thermal plasma (NTP) has been used for purification of wastewater, although
      the underlying mechanisms of degradation of organic pollutants are still unknown.
      In this study we employ two needle-type atmospheric pressure non-thermal plasma
      jets, i.e., indirect (ID-APPJ) and direct (D-APPJ) jets operating at Ar feed gas,
      for the treatment of methylene blue, methyl orange and congo red dyes, for two
      different times (i.e., 20 min and 30 min). Specifically, we study the
      decolorization/degradation of all three dyes using the above mentioned plasma
      sources, by means of UV-Vis spectroscopy, HPLC and a density meter. We also
      employ mass spectroscopy to verify whether only decolorization or also
      degradation takes place after treatment of the dyes by the NTP jets.
      Additionally, we analyze the interaction of OH radicals with all three dyes using
      reactive molecular dynamics simulations, based on the density functional-tight
      binding method. This investigation represents the first report on the degradation
      of these three different dyes by two types of NTP setups, analyzed by various
      methods, and based on both experimental and computational studies.

PMID- 27708353
TI  - Characterization of the DNA dependent activation of human ARTD2/PARP2.
AB  - Human ADP-ribosyltransferase 2 (ARTD2/PARP2) is an enzyme catalyzing a post
      translational modification, ADP-ribosylation. It is one of the three DNA
      dependent ARTDs in the 17 member enzyme family. ADP-ribosylation catalyzed by
      ARTD2 is involved in the regulation of multiple cellular processes such as
      control of chromatin remodeling, transcription and DNA repair. Here we used a
      combination of biochemical and biophysical methods to elucidate the structure and
      function of ARTD2. The solution structures revealed the binding mode of the ARTD2
      monomer and dimer to oligonucleotides that mimic damaged DNA. In the complex, DNA
      binds between the WGR domain and the catalytic fragment. The binding mode is
      supported by biophysical data that indicate all domains contribute to DNA
      binding. Also, our study showed that ARTD2 is preferentially activated by short
      5'-phosphorylated DNA oligonucleotides. We demonstrate that the N-terminus
      functions as a high-affinity DNA-binding module, while the WGR domain contributes
      to DNA binding specificity and subsequent catalytic activation. Our data further
      suggest that ARTD2 would function in double strand break repair as a dimeric
      module, while in single strand break repair it would function as a monomer.

PMID- 27708354
TI  - Plasticity mechanisms in HfN at elevated and room temperature.
AB  - HfN specimens deformed via four-point bend tests at room temperature and at 2300 
      degrees C (~0.7 Tm) showed increased plasticity response with temperature.
      Dynamic diffraction via transmission electron microscopy (TEM) revealed
      ?110?{111} as the primary slip system in both temperature regimes and ?110?{110}
      to be a secondary slip system activated at elevated temperature. Dislocation line
      lengths changed from a primarily linear to a curved morphology with increasing
      temperature suggestive of increased dislocation mobility being responsible for
      the brittle to ductile temperature transition. First principle generalized
      stacking fault energy calculations revealed an intrinsic stacking fault (ISF)
      along ?112?{111}, which is the partial dislocation direction for slip on these
      close packed planes. Though B1 structures, such as NaCl and HfC predominately
      slip on ?110?{110}, the ISF here is believed to facilitate slip on the {111}
      planes for this B1 HfN phase.

PMID- 27708355
TI  - Activation of Xer-recombination at dif: structural basis of the FtsKgamma-XerD
      interaction.
AB  - Bacterial chromosomes are most often circular DNA molecules. This can produce a
      topological problem; a genetic crossover from homologous recombination results in
      dimerization of the chromosome. A chromosome dimer is lethal unless resolved. A
      site-specific recombination system catalyses this dimer-resolution reaction at
      the chromosomal site dif. In Escherichia coli, two tyrosine-family recombinases,
      XerC and XerD, bind to dif and carry out two pairs of sequential strand exchange
      reactions. However, what makes the reaction unique among site-specific
      recombination reactions is that the first step, XerD-mediated strand exchange,
      relies on interaction with the very C-terminus of the FtsK DNA translocase. FtsK
      is a powerful molecular motor that functions in cell division, co-ordinating
      division with clearing chromosomal DNA from the site of septation and also acts
      to position the dif sites for recombination. This is a model system for
      unlinking, separating and segregating large DNA molecules. Here we describe the
      molecular detail of the interaction between XerD and FtsK that leads to
      activation of recombination as deduced from a co-crystal structure, biochemical
      and in vivo experiments. FtsKgamma interacts with the C-terminal domain of XerD,
      above a cleft where XerC is thought to bind. We present a model for activation of
      recombination based on structural data.

PMID- 27708356
TI  - Spatial genome organization and cognition.
AB  - Nonrandom chromosomal conformations, including promoter-enhancer loopings that
      bypass kilobases or megabases of linear genome, provide a crucial layer of
      transcriptional regulation and move vast amounts of non-coding sequence into the
      physical proximity of genes that are important for neurodevelopment, cognition
      and behaviour. Activity-regulated changes in the neuronal '3D genome' could
      govern transcriptional mechanisms associated with learning and plasticity, and
      loop-bound intergenic and intronic non-coding sequences have been implicated in
      psychiatric and adult-onset neurodegenerative disease. Recent studies have begun
      to clarify the roles of spatial genome organization in normal and abnormal
      cognition.

PMID- 27708357
TI  - Identification of TLR2/TLR6 signalling lactic acid bacteria for supporting immune
      regulation.
AB  - Although many lactic acid bacteria (LAB) influence the consumer's immune status
      it is not completely understood how this is established. Bacteria-host
      interactions between bacterial cell-wall components and toll-like receptors
      (TLRs) have been suggested to play an essential role. Here we investigated the
      interaction between LABs with reported health effects and TLRs. By using cell
      lines expressing single or combination of TLRs, we show that LABs can signal via
      TLR-dependent and independent pathways. The strains only stimulated and did not
      inhibit TLRs. We found that several strains such as L. plantarum CCFM634, L.
      plantarum CCFM734, L. fermentum CCFM381, L. acidophilus CCFM137, and S.
      thermophilus CCFM218 stimulated TLR2/TLR6. TLR2/TLR6 is essential in immune
      regulatory processes and of interest for prevention of diseases. Specificity of
      the TLR2/TLR6 stimulation was confirmed with blocking antibodies.
      Immunomodulatory properties of LABs were also studied by assessing IL-10 and IL-6
      secretion patterns in bacteria-stimulated THP1-derived macrophages, which
      confirmed species and strain specific effects of the LABs. With this study we
      provide novel insight in LAB specific host-microbe interactions. Our data
      demonstrates that interactions between pattern recognition receptors such as TLRs
      is species and strain specific and underpins the importance of selecting specific
      strains for promoting specific health effects.

PMID- 27708358
TI  - Increased Duodenal Eosinophil Degranulation in Patients with Functional
      Dyspepsia: A Prospective Study.
AB  - Functional dyspepsia (FD) is a functional gastrointestinal disorder diagnosed by
      symptom-based criteria. It has been said that duodenal immune activation plays a
      role in the pathogenesis of FD. The primary aims of the study were to compare the
      total number of duodenal eosinophil and evaluate the eosinophil degranulation
      rate, number of duodenal degranulated eosinophil and mast cell between patients
      with FD and healthy subjects. We enrolled 96 patients with FD and 24 healthy
      controls at Sir Run Run Shaw Hospital. The total number of eosinophil was
      comparable in the second portion of duodenum (D2) and duodenal bulb (D1) between
      patients with FD and healthy controls (all P > 0.05). Significant higher
      eosinophil degranulation positive rate in D2 (P = 0.003) and a trend towards
      higher in D1 (P = 0.084) were observed in patients with FD compared with healthy
      controls. Moreover, the number of duodenal degranulated eosinophil in patients
      with FD were significantly increased than healthy controls in D1(9.8 +/- 6.3 vs
      2.9 +/- 2.1 per HPF, P = 0.0002) and a trend towards increase in D2 (10.7 +/- 7.7
      vs 5.3 +/- 0.9 per HPF, P = 0.077), respectively. However, degranulated mast
      cells in patients with FD were almost same with healthy controls. Increased
      eosinophils degranulation in duodenum play an important role in pathogenesis of
      FD.

PMID- 27708359
TI  - Monolithic-Structured Single-Layered Textile-Based Dye-Sensitized Solar Cells.
AB  - Textile-structured solar cells are frequently discussed in the literature due to
      their prospective applications in wearable devices and in building integrated
      solar cells that utilize their flexibility, mechanical robustness, and aesthetic
      appearance, but the current approaches for textile-based solar cells-including
      the preparation of fibre-type solar cells woven into textiles-face several
      difficulties from high friction and tension during the weaving process. This
      study proposes a new structural concept and fabrication process for monolithic
      structured textile-based dye-sensitized solar cells that are fabricated by a
      process similar to the cloth-making process, including the preparation of wires
      and yarns that are woven for use in textiles, printed, dyed, and packaged. The
      fabricated single-layered textile-based dye-sensitized solar cells successfully
      act as solar cells in our study, even under bending conditions. By controlling
      the inter-weft spacing and the number of Ti wires for the photoelectrode
      conductor, we have found that the performance of this type of dye-sensitized
      solar cell was notably affected by the spacing between photoelectrodes and
      counter-electrodes, the exposed areas of Ti wires to photoelectrodes, and
      photoelectrodes' surface morphology. We believe that this study provides a
      process and concept for improved textile-based solar cells that can form the
      basis for further research.

PMID- 27708360
TI  - Grain Boundary Specific Segregation in Nanocrystalline Fe(Cr).
AB  - A cross-correlative precession electron diffraction - atom probe tomography
      investigation of Cr segregation in a Fe(Cr) nanocrystalline alloy was undertaken.
      Solute segregation was found to be dependent on grain boundary type. The results
      of which were compared to a hybrid Molecular Dynamics and Monte Carlo simulation
      that predicted the segregation for special character, low angle, and high angle
      grain boundaries, as well as the angle of inclination of the grain boundary. It
      was found that the highest segregation concentration was for the high angle grain
      boundaries and is explained in terms of clustering driven by the onset of phase
      separation. For special character boundaries, the highest Gibbsain interfacial
      excess was predicted at the incoherent ?3 followed by ?9 and ?11 boundaries with
      negligible segregation to the twin and ?5 boundaries. In addition, the low angle
      grain boundaries predicted negligible segregation. All of these trends matched
      well with the experiment. This solute-boundary segregation dependency for the
      special character grain boundaries is explained in terms of excess volume and the
      energetic distribution of the solute in the boundary.

PMID- 27708361
TI  - Infant-specific gaze patterns in response to radial optic flow.
AB  - The focus of a radial optic flow is a valid visual cue used to perceive and
      control the heading direction of animals. Gaze patterns in response to the focus
      of radial optic flow were measured in human infants (N = 100, 4-18 months) and in
      adults (N = 20) using an eye-tracking technique. Overall, although the adults
      showed an advantage in detecting the focus of an expansion flow (representing
      forward locomotion) against that of a contraction flow (representing backward
      locomotion), infants younger than 1 year showed an advantage in detecting the
      focus of a contraction flow. Infants aged between 13 and 18 months showed no
      significant advantage in detecting the focus in either the expansion or in the
      contraction flow. The uniqueness of the gaze patterns in response to the focus of
      radial optic flow in infants shows that the visual information necessary to
      perceive heading direction potentially differs between younger and mature
      individuals.

PMID- 27708362
TI  - Cystathionine gamma-lyase is expressed in human atherosclerotic plaque
      microvessels and is involved in micro-angiogenesis.
AB  - Atherosclerotic plaques are classically divided into stable and vulnerable
      plaques. Vulnerable plaques are prone to rupture with a risk for infarction. High
      intraplaque microvessel density predisposes to plaque vulnerability. Hydrogen
      sulfide (H2S) is a proangiogenic gasotransmitter which is endogenously produced
      by cystathionine gamma-lyase (CSE), and is believed to have vasculoprotective
      effects. However, due to its proangiogenic effects, H2S may result in
      pathological angiogenesis in atherosclerotic plaques, thereby increasing plaque
      vulnerability. The aim of this study was to determine CSE expression pattern in
      atherosclerotic plaques, and investigate whether CSE is involved in micro
      angiogenesis in vitro. Endarterectomy plaques were studied for CSE expression,
      and the role of CSE in micro-angiogenesis was studied in vitro. CSE is expressed
      in plaques with similar levels in both stable and vulnerable plaques. CSE co
      localized with von Willebrand Factor-positive microvessel endothelial cells and
      alpha-smooth-muscle actin-positive SMCs. In vitro, inhibition of CSE in HMEC-1
      reduced tube formation, cell viability/proliferation, and migration which was
      restored after culture in the presence of H2S donor GYY4137. CSE is expressed in
      intraplaque microvessels, and H2S is a stimulator of micro-angiogenesis in vitro.
      Due to this pro-angiogenic effect, high levels of CSE in atherosclerotic plaques
      may be a potential risk for plaque vulnerability.

PMID- 27708364
TI  - Orthotropic Piezoelectricity in 2D Nanocellulose.
AB  - The control of electromechanical responses within bonding regions is essential to
      face frontier challenges in nanotechnologies, such as molecular electronics and
      biotechnology. Here, we present Ibeta-nanocellulose as a potentially new
      orthotropic 2D piezoelectric crystal. The predicted in-layer piezoelectricity is
      originated on a sui-generis hydrogen bonds pattern. Upon this fact and by using a
      combination of ab-initio and ad-hoc models, we introduce a description of
      electrical profiles along chemical bonds. Such developments lead to obtain a
      rationale for modelling the extended piezoelectric effect originated within bond
      scales. The order of magnitude estimated for the 2D Ibeta-nanocellulose
      piezoelectric response, ~pm V-1, ranks this material at the level of currently
      used piezoelectric energy generators and new artificial 2D designs. Such finding
      would be crucial for developing alternative materials to drive emerging
      nanotechnologies.

PMID- 27708363
TI  - An rs4705342 T>C polymorphism in the promoter of miR-143/145 is associated with a
      decreased risk of ischemic stroke.
AB  - The expression of miR-143/miR-145 was up-regulated in ischemic stroke (IS), which
      may be used as biomarkers and/or therapeutic targets for IS. We aimed to
      investigate the association of rs4705342 and rs4705343 polymorphisms in the
      promoter of miR-143/145 with risk of IS. The study population comprised 445
      patients with IS and 518 controls. The rs4705342 genotype was analyzed by using a
      TaqMan Assay and the rs4705343 genotype was determined by using a polymerase
      chain reaction-restriction fragment length polymorphism assay. Relative
      expression of miR-143/miR-145 was measured by quantitative real-time PCR. We
      found that the rs4705342 was associated with a decreased risk of IS (TC vs. TT:
      adjusted OR = 0.74, 95% CI, 0.57-0.97; CC vs. TT: adjusted OR = 0.53, 95% CI,
      0.34-0.83). Haplotype analysis showed that the TC haplotype was associated with
      an increased risk of IS risk (OR = 1.33, 95% CI, 1.01-1.75), whereas the CT
      haplotype was associated with a decreased risk of IS risk (OR = 0.68, 95% CI,
      0.50-0.92). Importantly, patients carrying the rs4705342TC/CC genotypes had a
      lower level of miR-145 (P = 0.03). We found for the first time that the rs4705342
      CC was a protective factor for IS, probably by reducing the level of miR-145.

PMID- 27708365
TI  - Chimpanzees can visually perceive differences in the freshness of foods.
AB  - Colour vision in primates is believed to be an adaptation for finding ripe fruit
      and young leaves. The contribution of the luminance distribution, which
      influences how humans evaluate the freshness of food, has not been explored with
      respect to the detection of subtle distinctions in food quality in non-human
      primates. We examined how chimpanzees, which are closely related to humans,
      perceive the freshness of foods. The findings suggest that chimpanzees were able
      to choose fresher cabbage based on both colour and grey-scale images. Additional
      tests with images of novel cabbage, spinach, and strawberries revealed that one
      chimpanzee could detect the freshness of other fruits and vegetables. The
      critical factor in determining the judgements of freshness made by the
      chimpanzees was the spatial layout of luminance information. These findings
      provide the first known evidence that chimpanzees discriminate between images
      representing various degrees of freshness based solely on luminance information.

PMID- 27708366
TI  - Biotransformation of ferulic acid to vanillin in the packed bed-stirred
      fermentors.
AB  - We performed the biotransformation of ferulic acid to vanillin using Bacillus
      subtilis (B. subtilis) in the stirring packed-bed reactors filled with carbon
      fiber textiles (CFT). Scanning electron microscope (SEM), HPLC, qRT-PCR and ATP
      assay indicated that vanillin biotransformation is tightly related to cell
      growth, cellar activity and the extent of biofilm formation. The
      biotransformation was affected by hydraulic retention time (HRT), temperature,
      initial pH, stirring speed and ferulic acid concentration, and the maximum
      vanillin production was obtained at 20 h, 35  degrees C, 9.0, 200 rpm, 1.5 g/L,
      respectively. Repeated batch biotransformation performed under this optimized
      condition showed that the maximum productivity (0.047 g/L/h) and molar yield
      (60.43%) achieved in immobilized cell system were 1.84 and 3.61 folds higher than
      those achieved in free cell system. Therefore, the stirring reactor packed with
      CFT carrier biofilm formed by B. subtilis represented a valid biocatalytic system
      for the production of vanillin.

PMID- 27708367
TI  - P[8] and P[4] Rotavirus Infection Associated with Secretor Phenotypes Among
      Children in South China.
AB  - Rotaviruses are known to recognize human histo-blood group antigens (HBGAs) as a
      host ligand that is believed to play an important role in rotavirus host
      susceptibility and host range. In this study, paired fecal and saliva samples
      collected from children with viral gastroenteritis, as well as paired serum and
      saliva samples collected from the general population in south China were studied
      to evaluate potential association between rotavirus infections and human HBGA
      phenotypes. Rotavirus was detected in 75 (28%) of 266 fecal samples and P[8]
      rotaviruses were found to be the predominant genotype. The HBGA phenotypes of the
      rotavirus-infected children were determined through their saliva samples.
      Secretor statuses were found to correlate with the risk of rotavirus infection
      and all P[8]/P[4] rotavirus infected children were secretors. Accordingly,
      recombinant VP8* proteins of the P[8]/P[4] rotaviruses bound saliva samples from
      secretor individuals. Furthermore, correlation between serum P[8]/P[4]-specific
      IgG and host Lewis and secretor phenotypes has been found among 206 studied serum
      samples. Our study supported the association between rotavirus infection and the
      host HBGA phenotypes, which would help further understanding of rotavirus host
      range and epidemiology.

PMID- 27708368
TI  - Evaluation of A Novel Split-Feeding Anaerobic/Oxic Baffled Reactor (A/OBR) For
      Foodwaste Anaerobic Digestate: Performance, Modeling and Bacterial Community.
AB  - To enhance the treatment efficiency from an anaerobic digester, a novel six
      compartment anaerobic/oxic baffled reactor (A/OBR) was employed. Two kinds of
      split-feeding A/OBRs R2 and R3, with influent fed in the 1st, 3rd and 5th
      compartment of the reactor simultaneously at the respective ratios of 6:3:1 and
      6:2:2, were compared with the regular-feeding reactor R1 when all influent was
      fed in the 1st compartment (control). Three aspects, the COD removal, the
      hydraulic characteristics and the bacterial community, were systematically
      investigated, compared and evaluated. The results indicated that R2 and R3 had
      similar tolerance to loading shock, but the R2 had the highest COD removal of
      91.6% with a final effluent of 345 mg/L. The mixing patterns in both split
      feeding reactors were intermediate between plug-flow and completely-mixed, with
      dead spaces between 8.17% and 8.35% compared with a 31.9% dead space in R1.
      Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE)
      analysis revealed that the split-feeding strategy provided a higher bacterial
      diversity and more stable bacterial community than that in the regular-feeding
      strategy. Further analysis indicated that Firmicutes, Bacteroidetes, and
      Proteobacteria were the dominant bacteria, among which Firmicutes and
      Bacteroidetes might be responsible for organic matter degradation and
      Proteobacteria for nitrification and denitrification.

PMID- 27708369
TI  - Increasing The Genetic Admixture of Available Lines of Human Pluripotent Stem
      Cells.
AB  - Human pluripotent stem cells (hPSCs) may significantly improve drug development
      pipeline, serving as an in vitro system for the identification of novel leads,
      and for testing drug toxicity. Furthermore, these cells may be used to address
      the issue of differential drug response, a phenomenon greatly influenced by
      genetic factors. This application depends on the availability of hPSC lines from
      populations with diverse ancestries. So far, it has been reported that most lines
      of hPSCs derived worldwide are of European or East Asian ancestries. We have
      established 23 lines of hPSCs from Brazilian individuals, and we report the
      analysis of their genomic ancestry. We show that embryo-derived PSCs are mostly
      of European descent, while induced PSCs derived from participants of a national
      wide Brazilian cohort study present high levels of admixed European, African and
      Native American genomic ancestry. Additionally, we use high density SNP data and
      estimate local ancestries, particularly those of CYP genes loci. Such information
      will be of key importance when interpreting variation among cell lines with
      respect to cellular phenotypes of interest. The availability of genetically
      admixed lines of hPSCs will be of relevance when setting up future in vitro
      studies of drug response.

PMID- 27708370
TI  - Structure-based discovery of potentially active semiochemicals for Cydia
      pomonella (L.).
AB  - The development of physiologically active semiochemicals is largely limited by
      the labor-consuming searching process. How to screen active semiochemicals
      efficiently is of significance to the extension of behavior regulation in pest
      control. Here pharmacophore modeling and shape-based virtual screening were
      combined to predict candidate ligands for Cydia pomonella pheromone binding
      protein 1 (CpomPBP1). Out of the predicted compounds, ETrME displayed the highest
      affinity to CpomPBP1. Further studies on the interaction between CpomPBP1 and
      ETrME, not only depicted the binding mode, but also revealed residues providing
      negative and positive contributions to the ETrME binding. Moreover, key residues
      involved in interacting with ETrME of CpomPBP1 were determined as well. These
      findings were significant to providing insights for the future searching and
      optimization of active semiochemicals.

PMID- 27708372
TI  - Design and fabrication of high-performance diamond triple-gate field-effect
      transistors.
AB  - The lack of large-area single-crystal diamond wafers has led us to downscale
      diamond electronic devices. Here, we design and fabricate a hydrogenated diamond
      (H-diamond) triple-gate metal-oxide-semiconductor field-effect transistor
      (MOSFET) to extend device downscaling and increase device output current. The
      device's electrical properties are compared with those of planar-type MOSFETs,
      which are fabricated simultaneously on the same substrate. The triple-gate
      MOSFET's output current (174.2 mA mm-1) is much higher than that of the planar
      type device (45.2 mA mm-1), and the on/off ratio and subthreshold swing are more
      than 108 and as low as 110 mV dec-1, respectively. The fabrication of these H
      diamond triple-gate MOSFETs will drive diamond electronic device development
      forward towards practical applications.

PMID- 27708371
TI  - The Important Role of Halogen Bond in Substrate Selectivity of Enzymatic
      Catalysis.
AB  - The use of halogen bond is widespread in drug discovery, design, and clinical
      trials, but is overlooked in drug biosynthesis. Here, the role of halogen bond in
      the nitrilase-catalyzed synthesis of ortho-, meta-, and para-chlorophenylacetic
      acid was investigated. Different distributions of halogen bond induced changes of
      substrate binding conformation and affected substrate selectivity. By engineering
      the halogen interaction, the substrate selectivity of the enzyme changed, with
      the implication that halogen bond plays an important role in biosynthesis and
      should be used as an efficient and reliable tool in enzymatic drug synthesis.

PMID- 27708373
TI  - GlycoMinestruct: a new bioinformatics tool for highly accurate mapping of the
      human N-linked and O-linked glycoproteomes by incorporating structural features.
AB  - Glycosylation plays an important role in cell-cell adhesion, ligand-binding and
      subcellular recognition. Current approaches for predicting protein glycosylation
      are primarily based on sequence-derived features, while little work has been done
      to systematically assess the importance of structural features to glycosylation
      prediction. Here, we propose a novel bioinformatics method called
      GlycoMinestruct(http://glycomine.erc.monash.edu/Lab/GlycoMine_Struct/) for
      improved prediction of human N- and O-linked glycosylation sites by combining
      sequence and structural features in an integrated computational framework with a
      two-step feature-selection strategy. Experiments indicated that GlycoMinestruct
      outperformed NGlycPred, the only predictor that incorporated both sequence and
      structure features, achieving AUC values of 0.941 and 0.922 for N- and O-linked
      glycosylation, respectively, on an independent test dataset. We applied
      GlycoMinestruct to screen the human structural proteome and obtained high
      confidence predictions for N- and O-linked glycosylation sites. GlycoMinestruct
      can be used as a powerful tool to expedite the discovery of glycosylation events
      and substrates to facilitate hypothesis-driven experimental studies.

PMID- 27708375
TI  - The detection accuracy of cone beam CT for osseous defects of the
      temporomandibular joint: a systematic review and meta-analysis.
AB  - The purpose of this review was to evaluate whether cone-beam computed tomography
      (CBCT) is reliable for the detection of bone changes of the temporomandibular
      joint (TMJ). Studies collected from the PubMed, Web of Science, Cochrane Library,
      ScienceDirect, Embase, Wanfang and CNKI databases were searched, and the
      publishing time was limited from January 1990 to December 2015. Eight studies (23
      experimental research groups) were eventually included for further analysis. The
      pooled sensitivity was 0.67 and the pooled specificity was 0.87, which leads to a
      relatively large area (0.84) under the Receiver Operating Characteristic (ROC)
      curve. The related pooled positive likelihood ratio (+LR) and the pooled negative
      likelihood ratio (-LR) were 5.2 and 0.38, respectively. The subgroup analysis was
      conducted for four subgroups categorized by voxel size (<=0.2; >0.2, <=0.3; >0.3,
      <=0.4; >0.4, and <=0.5 (mm)), and the ">0.4, <=0.5" subgroup had a higher pooled
      sensitivity and pooled specificity than the other groups. The present study
      demonstrates that CBCT has a relatively high diagnostic accuracy for TMJ bone
      changes, although its reliability is limited. Voxel size did not play a role in
      the accuracy of CBCT.

PMID- 27708374
TI  - A transgenic approach to control hemipteran insects by expressing insecticidal
      genes under phloem-specific promoters.
AB  - The first generation transgenic crops used strong constitutive promoters for
      transgene expression. However, tissue-specific expression is desirable for more
      precise targeting of transgenes. Moreover, piercing/sucking insects, which are
      generally resistant to insecticidal Bacillus thuringiensis (Bt) proteins, have
      emerged as a major pests since the introduction of transgenic crops expressing
      these toxins. Phloem-specific promoters isolated from Banana bunchy top virus
      (BBTV) were used for the expression of two insecticidal proteins, Hadronyche
      versuta (Blue Mountains funnel-web spider) neurotoxin (Hvt) and onion leaf
      lectin, in tobacco (Nicotiana tabacum). Here we demonstrate that transgenic
      plants expressing Hvt alone or in combination with onion leaf lectin are
      resistant to Phenacoccus solenopsis (cotton mealybug), Myzus persicae (green
      peach aphids) and Bemisia tabaci (silver leaf whitefly). The expression of both
      proteins under different phloem-specific promoters resulted in close to 100%
      mortality and provided more rapid protection than Hvt alone. Our results suggest
      the employment of the Hvt and onion leaf lectin transgenic constructs at the
      commercial level will reduce the use of chemical pesticides for control of
      hemipteran insect pests.

PMID- 27708376
TI  - Clinical associations of IL-10 and IL-37 in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized
      by the development of autoantibodies to nuclear antigens and inflammatory
      responses mediated by multiple cytokines. Although previous studies have
      determined clinical associations between SLE and the anti-inflammatory cytokines
      IL-10 and IL-37, their role in the disease, or their potential as biomarkers,
      remains unclear. We examined serum levels of IL-10 and IL-37 in a large cohort of
      SLE patients, with detailed longitudinal clinical data. We demonstrate a
      statistically significant association of serum IL-10 with disease activity, with
      higher levels in active compared to inactive disease. High first visit IL-10 was
      predictive of high subsequent disease activity; patients with IL-10 in highest
      quartile at first visit were 3.6 times more likely to have active disease in
      subsequent visits. Serum IL-37 was also higher in SLE patients compared to
      control, and was strongly associated with Asian ethnicity. However, IL-37 was not
      statistically significantly associated with disease activity. IL-37 was
      significantly reduced in patients with organ damage but this association was
      attenuated in multivariable analysis. The data suggest that IL-10, but not IL-37,
      may have potential as a biomarker predictive for disease activity in SLE.

PMID- 27708377
TI  - Postoperative hormonal therapy prevents recovery of neurological damage after
      surgery in patients with breast cancer.
AB  - Cancer survivors are exposed to several risk factors for cognitive dysfunction,
      such as general anesthesia, surgical trauma, and adjuvant therapies. In our
      recent study we showed that thalamic volume reduction and attentional dysfunction
      occurred shortly after surgery. Here, we examined the 6-month prognosis of the 20
      patients with breast cancer who underwent surgery. Seven patients did not receive
      any adjuvant therapy after the surgery and 13 patients received a hormonal
      therapy after the surgery. We assessed their attentional functions, and thalamic
      volumes shortly after and 6 months after surgery. We found a significant group x
      time interaction in the attentional functions (p = 0.033) and the right thalamus
      (p <  0.05, small volume correction), suggesting the thalamic volume reduction
      and attentional dysfunction recovered in patients without adjuvant therapy. Our
      findings provide a better understanding of the potential role of hormonal therapy
      in relation to the cognitive dysfunction of cancer survivors.

PMID- 27708378
TI  - Electrochemical noise and impedance of Au electrode/electrolyte interfaces
      enabling extracellular detection of glioma cell populations.
AB  - Microelectrode arrays (MEA) record extracellular local field potentials of cells
      adhered to the electrodes. A disadvantage is the limited signal-to-noise ratio.
      The state-of-the-art background noise level is about 10 MUVpp. Furthermore, in
      MEAs low frequency events are filtered out. Here, we quantitatively analyze Au
      electrode/electrolyte interfaces with impedance spectroscopy and noise
      measurements. The equivalent circuit is the charge transfer resistance in
      parallel with a constant phase element that describes the double layer
      capacitance, in series with a spreading resistance. This equivalent circuit leads
      to a Maxwell-Wagner relaxation frequency, the value of which is determined as a
      function of electrode area and molarity of an aqueous KCl electrolyte solution.
      The electrochemical voltage and current noise is measured as a function of
      electrode area and frequency and follow unambiguously from the measured
      impedance. By using large area electrodes the noise floor can be as low as 0.3
      MUVpp. The resulting high sensitivity is demonstrated by the extracellular
      detection of C6 glioma cell populations. Their minute electrical activity can be
      clearly detected at a frequency below about 10 Hz, which shows that the
      methodology can be used to monitor slow cooperative biological signals in cell
      populations.

PMID- 27708379
TI  - High-speed and high-SNR photoacoustic microscopy based on a galvanometer mirror
      in non-conducting liquid.
AB  - Optical-resolution photoacoustic microscopy (OR-PAM), a promising microscopic
      imaging technique with high ultrasound resolution and superior optical
      sensitivity, can provide anatomical, functional, and molecular information at
      scales ranging from the microvasculature to single red blood cells. In
      particular, real-time OR-PAM imaging with a high signal-to-noise ratio (SNR) is a
      prerequisite for widespread use in preclinical and clinical applications.
      Although several technical approaches have been pursued to simultaneously improve
      the imaging speed and SNR of OR-PAM, they are bulky, complex, not sensitive,
      and/or not actually real-time. In this paper, we demonstrate a simple and novel
      OR-PAM technique which is based on a typical galvanometer immersed in non
      conducting liquid. Using an opto-ultrasound combiner, this OR-PAM system achieves
      a high SNR and fast imaging speed. It takes only 2 seconds to acquire a
      volumetric image with a wide field of view (FOV) of 4 * 8 mm2 along the X and Y
      axes, respectively. The measured lateral and axial resolutions are 6.0 and 37.7
      MUm, respectively. Finally, as a demonstration of the system's capability, we
      successfully imaged the microvasculature in a mouse ear in vivo. Our new method
      will contribute substantially to the popularization and commercialization of OR
      PAM in various preclinical and clinical applications.

PMID- 27708380
TI  - Two-photon interference of temporally separated photons.
AB  - We present experimental demonstrations of two-photon interference involving
      temporally separated photons within two types of interferometers: a Mach-Zehnder
      interferometer and a polarization-based Michelson interferometer. The two-photon
      states are probabilistically prepared in a symmetrically superposed state within
      the two interferometer arms by introducing a large time delay between two input
      photons; this state is composed of two temporally separated photons, which are in
      two different or the same spatial modes. We then observe two-photon interference
      fringes involving both the Hong-Ou-Mandel interference effect and the
      interference of path-entangled two-photon states simultaneously in a single
      interferometric setup. The observed two-photon interference fringes provide
      simultaneous observation of the interferometric properties of the single-photon
      and two-photon wavepackets. The observations can also facilitate a more
      comprehensive understanding of the origins of the interference phenomena arising
      from spatially bunched/anti-bunched two-photon states comprised of two temporally
      separated photons within the interferometer arms.

PMID- 27708381
TI  - Weighted and directed interactions in evolving large-scale epileptic brain
      networks.
AB  - Epilepsy can be regarded as a network phenomenon with functionally and/or
      structurally aberrant connections in the brain. Over the past years, concepts and
      methods from network theory substantially contributed to improve the
      characterization of structure and function of these epileptic networks and thus
      to advance understanding of the dynamical disease epilepsy. We extend this
      promising line of research and assess-with high spatial and temporal resolution
      and using complementary analysis approaches that capture different
      characteristics of the complex dynamics-both strength and direction of
      interactions in evolving large-scale epileptic brain networks of 35 patients that
      suffered from drug-resistant focal seizures with different anatomical onset
      locations. Despite this heterogeneity, we find that even during the seizure-free
      interval the seizure onset zone is a brain region that, when averaged over time,
      exerts strongest directed influences over other brain regions being part of a
      large-scale network. This crucial role, however, manifested by averaging on the
      population-sample level only - in more than one third of patients, strongest
      directed interactions can be observed between brain regions far off the seizure
      onset zone. This may guide new developments for individualized diagnosis,
      treatment and control.

PMID- 27708382
TI  - Temperature controls organic carbon sequestration in a subarctic lake.
AB  - Widespread ecological reorganizations and increases in organic carbon (OC) in
      lakes across the Northern Hemisphere have raised concerns about the impact of the
      ongoing climate warming on aquatic ecosystems and carbon cycling. We employed
      diverse biogeochemical techniques on a high-resolution sediment record from a
      subarctic lake in northern Finland (70 degrees N) to examine the direction,
      magnitude and mechanism of change in aquatic carbon pools prior to and under the
      anthropogenic warming. Coupled variation in the elemental and isotopic
      composition of the sediment and a proxy-based summer air temperature
      reconstruction tracked changes in aquatic production, depicting a decline during
      a cool climate interval between ~1700-1900 C.E. and a subsequent increase over
      the 20th century. OC accumulation rates displayed similar coeval variation with
      temperature, mirroring both changes in aquatic production and terrestrial carbon
      export. Increase in sediment organic content over the 20th century together with
      high inferred aquatic UV exposure imply that the 20th century increase in OC
      accumulation is primarily connected to elevated lake production rather than
      terrestrial inputs. The changes in the supply of autochthonous energy sources
      were further reflected higher up the benthic food web, as evidenced by biotic
      stable isotopic fingerprints.

PMID- 27708383
TI  - Evidence for nuclear interaction of a cytoskeleton protein (OsIFL) with
      metallothionein and its role in salinity stress tolerance.
AB  - Soil salinity is being perceived as a major threat to agriculture. Plant breeders
      and molecular biologist are putting their best efforts to raise salt-tolerant
      crops. The discovery of the Saltol QTL, a major QTL localized on chromosome I,
      responsible for salt tolerance at seedling stage in rice has given new hopes for
      raising salinity tolerant rice genotypes. In the present study, we have
      functionally characterized a Saltol QTL localized cytoskeletal protein,
      intermediate filament like protein (OsIFL), of rice. Studies related to
      intermediate filaments are emerging in plants, especially with respect to their
      involvement in abiotic stress response. Our investigations clearly establish that
      the heterologous expression of OsIFL in three diverse organisms (bacteria, yeast
      and tobacco) provides survival advantage towards diverse abiotic stresses.
      Screening of rice cDNA library revealed OsIFL to be strongly interacting with
      metallothionein protein. Bimolecular fluorescence complementation assay further
      confirmed this interaction to be occurring inside the nucleus. Overexpression of
      OsIFL in transgenic tobacco plants conferred salinity stress tolerance by
      maintaining favourable K+/Na+ ratio and thus showed protection from salinity
      stress induced ion toxicity. This study provides the first evidence for the
      involvement of a cytoskeletal protein in salinity stress tolerance in diverse
      organisms.

PMID- 27708384
TI  - Aptamer-conjugated live human immune cell based biosensors for the accurate
      detection of C-reactive protein.
AB  - C-reactive protein (CRP) is a pentameric protein that is present in the
      bloodstream during inflammatory events, e.g., liver failure, leukemia, and/or
      bacterial infection. The level of CRP indicates the progress and prognosis of
      certain diseases; it is therefore necessary to measure CRP levels in the blood
      accurately. The normal concentration of CRP is reported to be 1-3 mg/L.
      Inflammatory events increase the level of CRP by up to 500 times; accordingly,
      CRP is a biomarker of acute inflammatory disease. In this study, we demonstrated
      the preparation of DNA aptamer-conjugated peripheral blood mononuclear cells (Apt
      PBMCs) that specifically capture human CRP. Live PBMCs functionalized with
      aptamers could detect different levels of human CRP by producing immune complexes
      with reporter antibody. The binding behavior of Apt-PBMCs toward highly
      concentrated CRP sites was also investigated. The immune responses of Apt-PBMCs
      were evaluated by measuring TNF-alpha secretion after stimulating the PBMCs with
      lipopolysaccharides. In summary, engineered Apt-PBMCs have potential applications
      as live cell based biosensors and for in vitro tracing of CRP secretion sites.

PMID- 27708386
TI  - Low viscosity and high attenuation in MgSiO3 post-perovskite inferred from atomic
      scale calculations.
AB  - This work represents a numerical study of the thermal activation for dislocation
      glide of the [100](010) slip system in MgSiO3 post-perovskite (Mg-ppv) at 120
      GPa. We propose an approach based on a one-dimensional line tension model in
      conjunction with atomic-scale calculations. In this model, the key parameters,
      namely, the line tension and the Peierls barrier, are obtained from density
      functional theory calculations. We find a Peierls stress sigmap = 2.1 GPa and a
      line tension Gamma = 9.2 eV/A, which lead to a kink-pair enthalpy (under zero
      stress) of 2.69 eV. These values confirm that this slip system bears a very low
      lattice friction because it vanishes for temperatures above approximately 500 K
      under mantle conditions. In the Earth's mantle, high-pressure Mg-ppv silicate is
      thus expected to become as ductile as ferropericlase. These results confirm the
      hypothesis of a weak layer in the D" layer where Mg-ppv is present. Easy glide
      along [100](010) suggests strong preferred orientations with (010) planes
      aligned. Highly mobile [100] dislocations are also likely to respond to stresses
      related to seismic waves, leading to energy dissipation and strong attenuation.

PMID- 27708385
TI  - Bst1 is required for Candida albicans infecting host via facilitating cell wall
      anchorage of Glycosylphosphatidyl inositol anchored proteins.
AB  - Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are
      essential for invasive infections. While the function of inositol deacylation of
      GPI-APs in mammalian cells has been previously characterized the impact of
      inositol deacylation in fungi and implications to host infection remains largely
      unexplored. Herein we describe our identification of BST1, an inositol deacylase
      of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and
      host infection. BST1-deficient C. albicans (bst1Delta/Delta) was associated with
      severely impaired cell wall anchorage of GPI-APs and subsequen unmasked beta
      (1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Delta/Delta
      strain did not display an invasive ability and could be recognized more
      efficiently by host immune systems. Moreover, BST1 null mutants or those
      expressing Bst1 variants did not display inositol deacylation activity and
      exhibited severely attenuated virulence and reduced organic colonization in a
      murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage
      of GPI-APs in C. albicans by inositol deacylation, and is critical for host
      invasion and immune escape.

PMID- 27708387
TI  - Plant growth promoting rhizobacteria Dietzia natronolimnaea modulates the
      expression of stress responsive genes providing protection of wheat from salinity
      stress.
AB  - Plant growth promoting rhizobacteria (PGPR) hold promising future for sustainable
      agriculture. Here, we demonstrate a carotenoid producing halotolerant PGPR
      Dietzia natronolimnaea STR1 protecting wheat plants from salt stress by
      modulating the transcriptional machinery responsible for salinity tolerance in
      plants. The expression studies confirmed the involvement of ABA-signalling
      cascade, as TaABARE and TaOPR1 were upregulated in PGPR inoculated plants leading
      to induction of TaMYB and TaWRKY expression followed by stimulation of expression
      of a plethora of stress related genes. Enhanced expression of TaST, a salt stress
      induced gene, associated with promoting salinity tolerance was observed in PGPR
      inoculated plants in comparison to uninoculated control plants. Expression of SOS
      pathway related genes (SOS1 and SOS4) was modulated in PGPR-applied wheat shoots
      and root systems. Tissue-specific responses of ion transporters TaNHX1, TaHAK,
      and TaHKT1, were observed in PGPR-inoculated plants. The enhanced gene expression
      of various antioxidant enzymes such as APX, MnSOD, CAT, POD, GPX and GR and
      higher proline content in PGPR-inoculated wheat plants contributed to increased
      tolerance to salinity stress. Overall, these results indicate that halotolerant
      PGPR-mediated salinity tolerance is a complex phenomenon that involves modulation
      of ABA-signalling, SOS pathway, ion transporters and antioxidant machinery.

PMID- 27708388
TI  - The genetic map of goldfish (Carassius auratus) provided insights to the
      divergent genome evolutions in the Cyprinidae family.
AB  - A high-density linkage map of goldfish (Carassius auratus) was constructed using
      RNA-sequencing. This map consists of 50 linkage groups with 8,521 SNP markers and
      an average resolution of 0.62 cM. Approximately 84% of markers are in protein
      coding genes orthologous to zebrafish proteins. We performed comparative genome
      analysis between zebrafish and medaka, common carp, grass carp, and goldfish to
      study the genome evolution events in the Cyprinidae family. The comparison
      revealed large synteny blocks among Cyprinidae fish and we hypothesized that the
      Cyprinidae ancestor undergone many inter-chromosome rearrangements after
      speciation from teleost ancestor. The study also showed that goldfish genome had
      one more round of whole genome duplication (WGD) than zebrafish. Our results
      illustrated that most goldfish markers were orthologous to genes in common carp,
      which had four rounds of WGD. Growth-related regions and genes were identified by
      QTL analysis and association study. Function annotations of the associated genes
      suggested that they might regulate development and growth in goldfish. This first
      genetic map enables us to study the goldfish genome evolution and provides an
      important resource for selective breeding of goldfish.

PMID- 27708389
TI  - Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal
      Stem Cell Osteogenesis, Morphology, and Stiffness.
AB  - Mesenchymal stem cells (MSC) responding to mechanical cues generated by physical
      activity is critical for skeletal development and remodeling. Here, we utilized
      low intensity vibrations (LIV) as a physiologically relevant mechanical signal
      and hypothesized that the confined cytoskeletal configuration imposed by 2D
      culture will enable human bone marrow MSCs (hBMSC) to respond more robustly when
      LIV is applied in-plane (horizontal-LIV) rather than out-of-plane (vertical-LIV).
      All LIV signals enhanced hBMSC proliferation, osteogenic differentiation, and
      upregulated genes associated with cytoskeletal structure. The cellular response
      was more pronounced at higher frequencies (100 Hz vs 30 Hz) and when applied in
      the horizontal plane. Horizontal but not vertical LIV realigned the cell
      cytoskeleton, culminating in increased cell stiffness. Our results show that
      applying very small oscillatory motions within the primary cell attachment plane,
      rather than perpendicular to it, amplifies the cell's response to LIV, ostensibly
      facilitating a more effective transfer of intracellular forces. Transcriptional
      and structural changes in particular with horizontal LIV, together with the
      strong frequency dependency of the signal, emphasize the importance of
      intracellular cytoskeletal configuration in sensing and responding to high
      frequency mechanical signals at low intensities.

PMID- 27708390
TI  - Functional value of elytra under various stresses in the red flour beetle,
      Tribolium castaneum.
AB  - Coleoptera (beetles) is a massively successful order of insects, distinguished by
      their evolutionarily modified forewings called elytra. These structures are often
      presumed to have been a major driving force for the successful radiation of this
      taxon, by providing beetles with protection against a variety of harsh
      environmental factors. However, few studies have directly demonstrated the
      functional significance of the elytra against diverse environmental challenges.
      Here, we sought to empirically test the function of the elytra using Tribolium
      castaneum (the red flour beetle) as a model. We tested four categories of stress
      on the beetles: physical damage to hindwings, predation, desiccation, and cold
      shock. We found that, in all categories, the presence of elytra conferred a
      significant advantage compared to those beetles with their elytra experimentally
      removed. This work provides compelling quantitative evidence supporting the
      importance of beetle forewings in tolerating a variety of environmental stresses,
      and gives insight into how the evolution of elytra have facilitated the
      remarkable success of beetle radiation.

PMID- 27708391
TI  - Single cell dynamic phenotyping.
AB  - Live cell imaging has improved our ability to measure phenotypic heterogeneity.
      However, bottlenecks in imaging and image processing often make it difficult to
      differentiate interesting biological behavior from technical artifact. Thus there
      is a need for new methods that improve data quality without sacrificing
      throughput. Here we present a 3-step workflow to improve dynamic phenotype
      measurements of heterogeneous cell populations. We provide guidelines for image
      acquisition, phenotype tracking, and data filtering to remove erroneous cell
      tracks using the novel Tracking Aberration Measure (TrAM). Our workflow is
      broadly applicable across imaging platforms and analysis software. By applying
      this workflow to cancer cell assays, we reduced aberrant cell track prevalence
      from 17% to 2%. The cost of this improvement was removing 15% of the well-tracked
      cells. This enabled detection of significant motility differences between cell
      lines. Similarly, we avoided detecting a false change in translocation kinetics
      by eliminating the true cause: varied proportions of unresponsive cells. Finally,
      by systematically seeking heterogeneous behaviors, we detected subpopulations
      that otherwise could have been missed, including early apoptotic events and pre
      mitotic cells. We provide optimized protocols for specific applications and step
      by-step guidelines for adapting them to a variety of biological systems.

PMID- 27708392
TI  - Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic
      analysis.
AB  - The human gut microbiota varies considerably among world populations due to a
      variety of factors including genetic background, diet, cultural habits and
      socioeconomic status. Here we characterized 110 healthy Mongolian adults gut
      microbiota by shotgun metagenomic sequencing and compared the intestinal
      microbiome among Mongolians, the Hans and European cohorts. The results showed
      that the taxonomic profile of intestinal microbiome among cohorts revealed the
      Actinobaceria and Bifidobacterium were the key microbes contributing to the
      differences among Mongolians, the Hans and Europeans at the phylum level and
      genus level, respectively. Metagenomic species analysis indicated that
      Faecalibacterium prausnitzii and Coprococcus comeswere enrich in Mongolian people
      which might contribute to gut health through anti-inflammatory properties and
      butyrate production, respectively. On the other hand, the enriched genus
      Collinsella, biomarker in symptomatic atherosclerosis patients, might be
      associated with the high morbidity of cardiovascular and cerebrovascular diseases
      in Mongolian adults. At the functional level, a unique microbial metabolic
      pathway profile was present in Mongolian's gut which mainly distributed in amino
      acid metabolism, carbohydrate metabolism, energy metabolism, lipid metabolism,
      glycan biosynthesis and metabolism. We can attribute the specific signatures of
      Mongolian gut microbiome to their unique genotype, dietary habits and living
      environment.

PMID- 27708393
TI  - Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine
      morphology.
AB  - Dendritic spines are the postsynaptic compartments of glutamatergic synapses in
      the brain. Their number and shape are subject to change in synaptic plasticity
      and neurological disorders including autism spectrum disorders and Parkinson's
      disease. The L-type calcium channel CaV1.3 constitutes an important calcium entry
      pathway implicated in the regulation of spine morphology. Here we investigated
      the importance of full-length CaV1.3L and two C-terminally truncated splice
      variants (CaV1.342A and CaV1.343S) and their modulation by densin-180 and shank1b
      for the morphology of dendritic spines of cultured hippocampal neurons. Live-cell
      immunofluorescence and super-resolution microscopy of epitope-tagged CaV1.3L
      revealed its localization at the base-, neck-, and head-region of dendritic
      spines. Expression of the short splice variants or deletion of the C-terminal PDZ
      binding motif in CaV1.3L induced aberrant dendritic spine elongation. Similar
      morphological alterations were induced by co-expression of densin-180 or shank1b
      with CaV1.3L and correlated with increased CaV1.3 currents and dendritic calcium
      signals in transfected neurons. Together, our findings suggest a key role of
      CaV1.3 in regulating dendritic spine structure. Under physiological conditions it
      may contribute to the structural plasticity of glutamatergic synapses.
      Conversely, altered regulation of CaV1.3 channels may provide an important
      mechanism in the development of postsynaptic aberrations associated with
      neurodegenerative disorders.

PMID- 27708395
TI  - A hybrid tunable THz metadevice using a high birefringence liquid crystal.
AB  - We investigate a hybrid re-configurable three dimensional metamaterial based on
      liquid crystal as tuning element in order to build novel devices operating in the
      terahertz range. The proposed metadevice is an array of meta-atoms consisting of
      split ring resonators having suspended conducting cantilevers in the gap region.
      Adding a "third dimension" to a standard planar device plays a dual role: (i)
      enhance the tunability of the overall structure, exploiting the birefringence of
      the liquid crystal at its best, and (ii) improve the field confinement and
      therefore the ability of the metadevice to efficiently steer the THz signal. We
      describe the design, electromagnetic simulation, fabrication and experimental
      characterization of this new class of tunable metamaterials under an externally
      applied small voltage. By infiltrating tiny quantities of a nematic liquid
      crystal in the structure, we induce a frequency shift in the resonant response of
      the order of 7-8% in terms of bandwidth and about two orders of magnitude change
      in the signal absorption. We discuss how such a hybrid structure can be exploited
      for the development of a THz spatial light modulator.

PMID- 27708394
TI  - Fragment-based de novo design of a cystathionine gamma-lyase selective inhibitor
      blocking hydrogen sulfide production.
AB  - Hydrogen sulfide is an essential catabolite that intervenes in the
      pathophysiology of several diseases from hypertension to stroke, diabetes and
      pancreatitis. It is endogenously synthesized mainly by two pyridoxal-5'-phosphate
      dependent enzymes involved in L-cysteine metabolism: cystathionine-beta-synthase
      (CBS) and cystathionine-gamma-lyase (CSE). Research in this field is currently
      impaired by the lack of pharmacological tools such as selective enzymatic
      inhibitors that could target specifically only one of these pathways. We used a
      novel approach based on a hybrid method that includes drug design, synthetic
      biology, metabolomics and pharmacological assays to rationally design a new
      inhibitor selective for the CSE enzyme. The identification of this compound opens
      new frontiers towards a better understanding of the role of CSE over CBS in the
      pathophysiology of diseases where a role for the H2S pathway has been proposed
      and the development of new lead compounds that could target the CSE enzyme.

PMID- 27708396
TI  - ERK/c-Jun Recruits Tet1 to Induce Zta Expression and Epstein-Barr Virus
      Reactivation through DNA Demethylation.
AB  - DNA demethylation plays an essential role in the reactivation of Epstein-Barr
      virus (EBV) from latency infection. However, it is unclear how epigenetic
      modification is initiated in responding to stimuli. Here, we demonstrate that
      ERK/c-Jun signaling is involved in DNA demethylation of EBV immediate early (IE)
      gene Zta in response to 12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulation.
      Remarkably, Ser73 phosphorylation of c-Jun facilitates Zta promoter demethylation
      and EBV reactivation, whereas knockdown of c-Jun attenuates Zta demethylation and
      viral reactivation. More importantly, we reveal for the first time that c-Jun
      interacts with DNA dioxygenase Tet1 and facilitates Tet1 to bind to Zta promoter.
      The binding of c-Jun and Tet1 to Zta enhances promoter demethylation, resulting
      in the activation of Zta, the stimulation of BHRF1 (a lytic early gene) and
      gp350/220 (a lytic late gene), and ultimately the reactivation of EBV. Knockdown
      of Tet1 attenuates TPA-induced Zta demethylation and EBV reactivation. Thus, TPA
      activates ERK/c-Jun signaling, which subsequently facilitates Tet1 to bind to Zta
      promoter, leading to DNA demethylation, gene expression, and EBV reactivation.
      This study reveals important roles of ERK/c-Jun signaling and Tet1 dioxygenase in
      epigenetic modification, and provides new insights into the mechanism underlying
      the regulation of virus latent and lytic infection.

PMID- 27708398
TI  - Unidirectional superscattering by multilayered cavities of effective radial
      anisotropy.
AB  - We achieve unidirectional forward superscattering by multilayered spherical
      cavities which are effectively radially anisotropic. It is demonstrated that,
      relying on the large effective anisotropy, the electric and magnetic dipoles can
      be tuned to spectrally overlap in such cavities, which satisfies the Kerker's
      condition of simultaneous backward scattering suppression and forward scattering
      enhancement. We show that such scattering pattern shaping can be obtained in both
      all-dielectric and plasmonic multilayered cavities at different spectral
      positions, and believe that the mechanism we have revealed provides extra freedom
      for scattering shaping, which may play a significant role in many scattering
      related applications and also in optoelectronic devices made up of intrinsically
      anisotropic two dimensional materials.

PMID- 27708397
TI  - CXCL13/CXCR5 enhances sodium channel Nav1.8 current density via p38 MAP kinase in
      primary sensory neurons following inflammatory pain.
AB  - CXCL13 is a B lymphocyte chemoattractant and activates CXCR5 receptor in the
      immune system. Here we investigated whether CXCL13/CXCR5 mediates inflammatory
      pain in dorsal root ganglia (DRG) and the underlying mechanisms. Peripheral
      injection of complete Freund's Adjuvant (CFA) increased the expression of CXCL13
      and CXCR5 in DRG neurons. In Cxcr5-/- mice, CFA-induced pain hypersensitivity
      were attenuated. Whole-cell patch-clamp recording showed that the excitability of
      dissociated DRG neurons was increased after CFA injection or CXCL13 incubation
      from wild-type (WT) mice, but not from Cxcr5-/- mice. Additionally, sodium
      channel Nav1.8 was co-expressed with CXCR5 in dissociated DRG neurons, and the
      increased neuronal excitability induced by CFA or CXCL13 was reduced by Nav1.8
      blocker. Intrathecal injection of Nav1.8 blocker also attenuated intrathecal
      injection of CXCL13-induced pain hypersensitivity. Furthermore, CXCL13 increased
      Nav1.8 current density in DRG neurons, which was inhibited by p38 MAP kinase
      inhibitor. CFA and CXCL13 increased p38 phosphorylation in the DRG of WT mice but
      not Cxcr5-/- mice. Finally, intrathecal p38 inhibitor alleviated CXCL13-induced
      pain hypersensitivity. Taken together, these results demonstrated that CXCL13,
      upregulated by peripheral inflammation, acts on CXCR5 on DRG neurons and
      activates p38, which increases Nav1.8 current density and further contributes to
      the maintenance of inflammatory pain.

PMID- 27708399
TI  - Controllable growth of vertically aligned graphene on C-face SiC.
AB  - We investigated how to control the growth of vertically aligned graphene on C
      face SiC by varying the processing conditions. It is found that, the growth rate
      scales with the annealing temperature and the graphene height is proportional to
      the annealing time. Temperature gradient and crystalline quality of the SiC
      substrates influence their vaporization. The partial vapor pressure is crucial as
      it can interfere with further vaporization. A growth mechanism is proposed in
      terms of physical vapor transport. The monolayer character of vertically aligned
      graphene is verified by Raman and X-ray absorption spectroscopy. With the
      processed samples, d0 magnetism is realized and negative magnetoresistance is
      observed after Cu implantation. We also prove that multiple carriers exist in
      vertically aligned graphene.

PMID- 27708400
TI  - Systemic sclerosis: The future is CD56-bright.

PMID- 27708401
TI  - Connective tissue diseases: Promises and challenges of metabolomics in SLE.

PMID- 27708402
TI  - Easy on-demand single-pass self-assembly and modification to fabricate
      gold@graphene-based anti-inflammatory nanoplatforms.
AB  - Zwitterionic chitosan (ZC) was modified by fully (both for lateral dimension and
      thickness) nanodimensional gold-graphene oxide (Au@GO) flakes under visible light
      and the potential of the resulting materials as biomedical nanoplatforms was
      investigated. Fully nanodimensional GO flakes floating in nitrogen gas were
      incorporated with Au nanoparticles to form Au@GO nanoflakes, and the Au@GO was
      then incorporated with ZC droplets to form the Au@GO-ZC hybrid nanoparticles. The
      collected particles were exposed to visible light to induce the photocatalytic
      activity of the Au@GO nanoflakes towards the ZC derivatives. The visible-light
      exposed particles show different chemical and surface properties from the
      unexposed particles, while there were no significant differences in cytotoxicity
      and macrophage inflammatory protein production. This work suggests that
      incorporating fully nanodimensional Au@GO flakes with ZC is a suitable technique
      for ambient photo-modification of the chitosans' surface property without
      significant changes in size and shape and increases in cytotoxicity and
      inflammatory response.

PMID- 27708403
TI  - Dissecting the contribution of Staphylococcus aureus alpha-phenol-soluble
      modulins to biofilm amyloid structure.
AB  - The opportunistic pathogen Staphylococcus aureus is recognized as one of the most
      frequent causes of biofilm-associated infections. The recently discovered phenol
      soluble modulins (PSMs) are small alpha-helical amphipathic peptides that act as
      the main molecular effectors of staphylococcal biofilm maturation, promoting the
      formation of an extracellular fibril structure with amyloid-like properties.
      Here, we combine computational, biophysical and in cell analysis to address the
      specific contribution of individual PSMs to biofilm structure. We demonstrate
      that despite their highly similar sequence and structure, contrary to what it was
      previously thought, not all PSMs participate in amyloid fibril formation. A
      balance of hydrophobic/hydrophilic forces and helical propensity seems to define
      the aggregation propensity of PSMs and control their assembly and function. This
      knowledge would allow to target specifically the amyloid properties of these
      peptides. In this way, we show that Epigallocatechin-3-gallate (EGCG), the
      principal polyphenol in green tea, prevents the assembly of amyloidogenic PSMs
      and disentangles their preformed amyloid fibrils.

PMID- 27708404
TI  - Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in
      5XFAD Mouse Model of Alzheimer's Disease.
AB  - MicroRNAs have emerged as key factors in development, neurogenesis and synaptic
      functions in the central nervous system. In the present study, we investigated a
      pathophysiological significance of microRNA-188-5p (miR-188-5p) in Alzheimer's
      disease (AD). We found that oligomeric Abeta1-42 treatment diminished miR-188-5p
      expression in primary hippocampal neuron cultures and that miR-188-5p rescued the
      Abeta1-42-mediated synapse elimination and synaptic dysfunctions. Moreover, the
      impairments in cognitive function and synaptic transmission observed in 7-month
      old five familial AD (5XFAD) transgenic mice, were ameliorated via viral-mediated
      expression of miR-188-5p. miR-188-5p expression was down-regulated in the brain
      tissues from AD patients and 5XFAD mice. The addition of miR-188-5p rescued the
      reduction in dendritic spine density in the primary hippocampal neurons treated
      with oligomeric Abeta1-42 and cultured from 5XFAD mice. The reduction in the
      frequency of mEPSCs was also restored by addition of miR-188-5p. The impairments
      in basal fEPSPs and cognition observed in 7-month-old 5XFAD mice were ameliorated
      via the viral-mediated expression of miR-188-5p in the hippocampus. Furthermore,
      we found that miR-188 expression is CREB-dependent. Taken together, our results
      suggest that dysregulation of miR-188-5p expression contributes to the
      pathogenesis of AD by inducing synaptic dysfunction and cognitive deficits
      associated with Abeta-mediated pathophysiology in the disease.

PMID- 27708405
TI  - A fragment-based approach applied to a highly flexible target: Insights and
      challenges towards the inhibition of HSP70 isoforms.
AB  - The heat shock protein 70s (HSP70s) are molecular chaperones implicated in many
      cancers and of significant interest as targets for novel cancer therapies.
      Several HSP70 inhibitors have been reported, but because the majority have poor
      physicochemical properties and for many the exact mode of action is poorly
      understood, more detailed mechanistic and structural insight into ligand-binding
      to HSP70s is urgently needed. Here we describe the first comprehensive fragment
      based inhibitor exploration of an HSP70 enzyme, which yielded an amino
      quinazoline fragment that was elaborated to a novel ATP binding site ligand with
      different physicochemical properties to known adenosine-based HSP70 inhibitors.
      Crystal structures of amino-quinazoline ligands bound to the different
      conformational states of the HSP70 nucleotide binding domain highlighted the
      challenges of a fragment-based approach when applied to this particular flexible
      enzyme class with an ATP-binding site that changes shape and size during its
      catalytic cycle. In these studies we showed that Ser275 is a key residue in the
      selective binding of ATP. Additionally, the structural data revealed a potential
      functional role for the ATP ribose moiety in priming the protein for the
      formation of the ATP-bound pre-hydrolysis complex by influencing the conformation
      of one of the phosphate binding loops.

PMID- 27708406
TI  - Structural and Functional Characterization of the VQ Protein Family and VQ
      Protein Variants from Soybean.
AB  - Proteins containing the FxxxVQxhTG or VQ motif interact with WRKY transcription
      factors. Although VQ proteins have been reported in several plants, knowledge
      about their structures, functions and evolution is still very limited. Here, we
      report structural and functional analysis of the VQ protein family from soybean.
      Like Arabidopsis homologues, soybean VQ proteins bind only Group I and IIc WRKY
      proteins and a substantial number of their genes are responsive to stress
      associated phytohormones. Overexpression of some soybean VQ genes in Arabidopsis
      had strong effects on plant growth, development, disease resistance and heat
      tolerance. Phylogenetic analysis, sequence alignment and site-directed
      mutagenesis revealed that the region immediately upstream of the FxxxVQxhTG motif
      also affects binding to WRKY proteins. Consistent with a larger WRKY-binding VQ
      domain, soybean VQ22 protein from cultivated soybean contains a 4-amino acid
      deletion in the region preceding its VQ motif that completely abolishes its
      binding to WRKY proteins. By contrast, the 4-amino acid deletion is absent in the
      VQ22 protein from wild soybean species (Glycine soja). Overexpression of wild
      soybean VQ22 in cultivated soybean inhibited growth, particularly after cold
      treatment. Thus, the mutation of soybean VQ22 is associated with advantageous
      phenotypes and may have been positively selected during evolution.

PMID- 27708407
TI  - Developing a genetic manipulation system for the Antarctic archaeon, Halorubrum
      lacusprofundi: investigating acetamidase gene function.
AB  - No systems have been reported for genetic manipulation of cold-adapted Archaea.
      Halorubrum lacusprofundi is an important member of Deep Lake, Antarctica (~10% of
      the population), and is amendable to laboratory cultivation. Here we report the
      development of a shuttle-vector and targeted gene-knockout system for this
      species. To investigate the function of acetamidase/formamidase genes, a class of
      genes not experimentally studied in Archaea, the acetamidase gene, amd3, was
      disrupted. The wild-type grew on acetamide as a sole source of carbon and
      nitrogen, but the mutant did not. Acetamidase/formamidase genes were found to
      form three distinct clades within a broad distribution of Archaea and Bacteria.
      Genes were present within lineages characterized by aerobic growth in low
      nutrient environments (e.g. haloarchaea, Starkeya) but absent from lineages
      containing anaerobes or facultative anaerobes (e.g. methanogens,
      Epsilonproteobacteria) or parasites of animals and plants (e.g. Chlamydiae).
      While acetamide is not a well characterized natural substrate, the build-up of
      plastic pollutants in the environment provides a potential source of introduced
      acetamide. In view of the extent and pattern of distribution of
      acetamidase/formamidase sequences within Archaea and Bacteria, we speculate that
      acetamide from plastics may promote the selection of amd/fmd genes in an
      increasing number of environmental microorganisms.

PMID- 27708410
TI  - Low Complexity Compression and Speed Enhancement for Optical Scanning Holography.
AB  - In this paper we report a low complexity compression method that is suitable for
      compact optical scanning holography (OSH) systems with different optical
      settings. Our proposed method can be divided into 2 major parts. First, an
      automatic decision maker is applied to select the rows of holographic pixels to
      be scanned. This process enhances the speed of acquiring a hologram, and also
      lowers the data rate. Second, each row of down-sampled pixels is converted into a
      one-bit representation with delta modulation (DM). Existing DM-based hologram
      compression techniques suffers from the disadvantage that a core parameter,
      commonly known as the step size, has to be determined in advance. However, the
      correct value of the step size for compressing each row of hologram is dependent
      on the dynamic range of the pixels, which could deviate significantly with the
      object scene, as well as OSH systems with different opical settings. We have
      overcome this problem by incorporating a dynamic step-size adjustment scheme. The
      proposed method is applied in the compression of holograms that are acquired with
      2 different OSH systems, demonstrating a compression ratio of over two orders of
      magnitude, while preserving favorable fidelity on the reconstructed images.

PMID- 27708408
TI  - PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation
      with reciprocal balance of Th17 and Tregs.
AB  - PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3
      activation. Recently, inactivation of STAT3 has been demonstrated as a
      therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled
      by p53 regulates autoimmune arthritis through modulating the balance between Th17
      and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity
      and inflammatory response via inhibiting STAT3 activation. Our results revealed
      that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3
      activity and Th17 differentiation. Systemic infusion of PTEN overexpression
      downregulated CIA severity. In addition, PTEN overexpression decreased the
      activation of T cells and modulated reciprocal differentiation of Th17 and Treg
      cells. We observed that PTEN expression downregulated by p53 deficiency induced
      the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and
      dysregulated the population of Th17 and Treg. These data suggest that induction
      of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid
      arthritis therapy.

PMID- 27708409
TI  - Hyperoxaluria leads to dysbiosis and drives selective enrichment of oxalate
      metabolizing bacterial species in recurrent kidney stone endures.
AB  - Hyperoxaluria due to endogenously synthesized and exogenously ingested oxalates
      is a leading cause of recurrent oxalate stone formations. Even though, humans
      largely rely on gut microbiota for oxalate homeostasis, hyperoxaluria associated
      gut microbiota features remain largely unknown. Based on 16S rRNA gene amplicons,
      targeted metagenomic sequencing of formyl-CoA transferase (frc) gene and qPCR
      assay, we demonstrate a selective enrichment of Oxalate Metabolizing Bacterial
      Species (OMBS) in hyperoxaluria condition. Interestingly, higher than usual
      concentration of oxalate was found inhibitory to many gut microbes, including
      Oxalobacter formigenes, a well-characterized OMBS. In addition a concomitant
      enrichment of acid tolerant pathobionts in recurrent stone sufferers is observed.
      Further, specific enzymes participating in oxalate metabolism are found augmented
      in stone endures. Additionally, hyperoxaluria driven dysbiosis was found to be
      associated with oxalate content, stone episodes and colonization pattern of
      Oxalobacter formigenes. Thus, we rationalize the first in-depth surveillance of
      OMBS in the human gut and their association with hyperoxaluria. Our findings can
      be utilized in the treatment of hyperoxaluria associated recurrent stone
      episodes.

PMID- 27708412
TI  - Steady flow and heat transfer analysis of Phan-Thein-Tanner fluid in double-layer
      optical fiber coating analysis with Slip Conditions.
AB  - Modern optical fibers require double-layer coating on the glass fiber to provide
      protection from signal attenuation and mechanical damage. The most important
      plastic resins used in wires and optical fibers are plastic polyvinyl chloride
      (PVC) and low-high density polyethylene (LDPE/HDPE), nylon and Polysulfone. In
      this paper, double-layer optical fiber coating is performed using melt polymer
      satisfying PTT fluid model in a pressure type die using wet-on-wet coating
      process. The assumption of fully developed flow of Phan-Thien-Tanner (PTT) fluid
      model, two-layer liquid flows of an immiscible fluid is modeled in an annular
      die, where the fiber is dragged at a higher speed. The equations characterizing
      the flow and heat transfer phenomena are solved exactly and the effects of
      emerging parameters (Deborah and slip parameters, characteristic velocity, radii
      ratio and Brinkman numbers on the axial velocity, flow rate, thickness of coated
      fiber optics, and temperature distribution) are reported in graphs. It is shown
      that an increase in the non-Newtonian parameters increase the velocity in the
      absence or presence of slip parameters which coincides with related work. The
      comparison is done with experimental work by taking lambda -> 0 (non-Newtonian
      parameter).

PMID- 27708411
TI  - DNA annealing by Redbeta is insufficient for homologous recombination and the
      additional requirements involve intra- and inter-molecular interactions.
AB  - Single strand annealing proteins (SSAPs) like Redbeta initiate homologous
      recombination by annealing complementary DNA strands. We show that C-terminally
      truncated Redbeta, whilst still able to promote annealing and nucleoprotein
      filament formation, is unable to mediate homologous recombination. Mutations of
      the C-terminal domain were evaluated using both single- and double stranded (ss
      and ds) substrates in recombination assays. Mutations of critical amino acids
      affected either dsDNA recombination or both ssDNA and dsDNA recombination
      indicating two separable functions, one of which is critical for dsDNA
      recombination and the second for recombination per se. As evaluated by co
      immunoprecipitation experiments, the dsDNA recombination function relates to the
      Redalpha-Redbeta protein-protein interaction, which requires not only contacts in
      the C-terminal domain but also a region near the N-terminus. Because the
      nucleoprotein filament formed with C-terminally truncated Redbeta has altered
      properties, the second C-terminal function could be due to an interaction
      required for functional filaments. Alternatively the second C-terminal function
      could indicate a requirement for a Redbeta-host factor interaction. These data
      further advance the model for Red recombination and the proposition that Redbeta
      and RAD52 SSAPs share ancestral and mechanistic roots.

PMID- 27708413
TI  - Normative data for the segmental acquisition of contact heat evoked potentials in
      cervical dermatomes.
AB  - Contact heat evoked potentials (CHEPs) represent a neurophysiological approach to
      assess conduction in the spinothalamic tract. The aim of this study was to
      establish normative values of CHEPs acquired from cervical dermatomes (C4, C6,
      C8) and examine the potential confounds of age, sex, and height. 101 (49 male)
      healthy subjects of three different age groups (18-40, 41-60, and 61-80 years)
      were recruited. Normal (NB, 35-52  degrees C) followed by increased (IB, 42-52 
      degrees C) baseline stimulation protocols were employed to record CHEPs. Multi
      variate linear models were used to investigate the effect of age, sex, and height
      on the CHEPs parameters (i.e., N2 latency, N2P2 amplitude, rating of perceived
      intensity). Compared to NB, IB stimulation reduced latency jitter within
      subjects, yielding larger N2P2 amplitudes, and decreased inter-subject N2 latency
      variability. Age was associated with reduced N2P2 amplitude and prolonged N2
      latency. After controlling for height, male subjects had significantly longer N2
      latencies than females during IB stimulation. The study provides normative CHEPs
      data in a large cohort of healthy subjects from segmentally examined cervical
      dermatomes. Age and sex were identified as important factors contributing to N2
      latency and N2P2 amplitude. The normative data will improve the diagnosis of
      spinal cord pathologies.

PMID- 27708415
TI  - High-Throughput Design of Two-Dimensional Electron Gas Systems Based on
      Polar/Nonpolar Perovskite Oxide Heterostructures.
AB  - The two-dimensional electron gas (2DEG) formed at the interface between two
      insulating oxides such as LaAlO3 and SrTiO3 (STO) is of fundamental and practical
      interest because of its novel interfacial conductivity and its promising
      applications in next-generation nanoelectronic devices. Here we show that a group
      of combinatorial descriptors that characterize the polar character, lattice
      mismatch, band gap, and the band alignment between the perovskite-oxide-based
      band insulators and the STO substrate, can be introduced to realize a high
      throughput (HT) design of SrTiO3-based 2DEG systems from perovskite oxide quantum
      database. Equipped with these combinatorial descriptors, we have carried out a HT
      screening of all the polar perovskite compounds, uncovering 42 compounds of
      potential interests. Of these, Al-, Ga-, Sc-, and Ta-based compounds can form a
      2DEG with STO, while In-based compounds exhibit a strain-induced strong
      polarization when deposited on STO substrate. In particular, the Ta-based
      compounds can form 2DEG with potentially high electron mobility at (TaO2)+/(SrO)0
      interface. Our approach, by defining materials descriptors solely based on the
      bulk materials properties, and by relying on the perovskite-oriented quantum
      materials repository, opens new avenues for the discovery of perovskite-oxide
      based functional interface materials in a HT fashion.

PMID- 27708414
TI  - Association between dietary patterns and metabolic syndrome in Chinese adults: a
      propensity score-matched case-control study.
AB  - Previous studies indicated that dietary patterns were associated with metabolic
      syndrome (MS), but little is known in Chinese. We design this case-control study
      to evaluate the associations between dietary patterns and MS in Chinese adults.
      In this study, 1492 participants with MS were matched with 1492 controls using
      the 1:1 ratio propensity score matching methods. Dietary intake was assessed
      using a valid self-administered food frequency questionnaire, and MS was defined
      in accordance with the criteria of the American Heart Association scientific
      statement of 2009. Higher scores for the high-protein/cholesterol pattern were
      associated with higher prevalence of MS. Compared with the participants in the
      lowest quartile, the odds ratio (OR) for the extreme quartile was 1.36 (95%
      confidence interval (CI), 1.10-1.68) and the P for trend <0.01 after adjusted for
      the other two dietary pattern scores. We also found a moderate consumption of the
      balanced pattern was associated with the lowest prevalence of MS. The ORs across
      quartiles of the balanced pattern were 1 (reference), 0.83 (95% CI, 0.68-1.02),
      0.69 (95% CI, 0.56-0.85), and 0.84 (95% CI, 0.68-1.04) after adjustment. Our
      study demonstrates that there is a strong association between a diet rich in
      animal offal, animal blood, meat, and sausage and a higher prevalence of MS.

PMID- 27708416
TI  - Loss of Atg16 delays the alcohol-induced sedation response via regulation of
      Corazonin neuropeptide production in Drosophila.
AB  - Autophagy defects lead to the buildup of damaged proteins and organelles, reduced
      survival during starvation and infections, hypersensitivity to stress and toxic
      substances, and progressive neurodegeneration. Here we show that, surprisingly,
      Drosophila mutants lacking the core autophagy gene Atg16 are not only defective
      in autophagy but also exhibit increased resistance to the sedative effects of
      ethanol, unlike Atg7 or Atg3 null mutant flies. This mutant phenotype is rescued
      by the re-expression of Atg16 in Corazonin (Crz)-producing neurosecretory cells
      that are known to promote the sedation response during ethanol exposure, and RNAi
      knockdown of Atg16 specifically in these cells also delays the onset of ethanol
      induced coma. We find that Atg16 and Crz colocalize within these neurosecretory
      cells, and both Crz protein and mRNA levels are decreased in Atg16 mutant flies.
      Thus, Atg16 promotes Crz production to ensure a proper organismal sedation
      response to ethanol.

PMID- 27708417
TI  - Critical Role of Transcription Factor PU.1 in the Function of the OX40L/TNFSF4
      Promoter in Dendritic Cells.
AB  - PU.1 is a hematopoietic lineage-specific transcription factor belonging to the
      Ets family. We investigated the role of PU.1 in the expression of OX40L in
      dendritic cells (DCs), because the regulatory mechanism of cell type-specific
      expression of OX40L, which is mainly restricted to antigen-presenting cells, is
      largely unknown despite the critical involvement in Th2 and Tfh development. PU.1
      knockdown decreased the expression of OX40L in mouse DCs. Chromatin
      immunoprecipitation (ChIP) assays demonstrated that PU.1 constitutively bound to
      the proximal region of the OX40L promoter. Reporter assays and electrophoretic
      mobility shift assays revealed that PU.1 transactivated the OX40L promoter
      through direct binding to the most-proximal Ets motif. We found that this Ets
      motif is conserved between mouse and human, and that PU.1 bound to the human
      OX40L promoter in ChIP assay using human monocyte-derived DCs. ChIP assays based
      on ChIP-seq datasets revealed that PU.1 binds to several sites distant from the
      transcription start site on the OX40L gene in addition to the most-proximal site
      in mouse DCs. In the present study, the structure of the OX40L promoter regulated
      by PU.1 is determined. It is also suggested that PU.1 is involved in mouse OX40L
      expression via multiple binding sites on the gene.

PMID- 27708418
TI  - B cell-derived transforming growth factor-beta1 expression limits the induction
      phase of autoimmune neuroinflammation.
AB  - Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of
      multiple sclerosis (MS), have shown that regulatory B cells modulate the course
      of the disease via the production of suppressive cytokines. While data indicate a
      role for transforming growth factor (TGF)-beta1 expression in regulatory B cell
      functions, this mechanism has not yet been tested in autoimmune
      neuroinflammation. Transgenic mice deficient for TGF-beta1 expression in B cells
      (B-TGF-beta1-/-) were tested in EAE induced by recombinant mouse myelin
      oligodendrocyte glycoprotein (rmMOG). In this model, B-TGF-beta1-/- mice showed
      an earlier onset of neurologic impairment compared to their littermate controls.
      Exacerbated EAE susceptibility in B-TGF-beta1-/- mice was associated with
      augmented CNS T helper (Th)1/17 responses. Moreover, selective B cell TGF-beta1
      deficiency increased the frequencies and activation of myeloid dendritic cells,
      potent professional antigen-presenting cells (APCs), suggesting that B cell
      derived TGF-beta1 can constrain Th1/17 responses through inhibition of APC
      activity. Collectively our data suggest that B cells can down-regulate the
      function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-beta1,
      findings that may be relevant to B cell-targeted therapies.

PMID- 27708421
TI  - Depth-distribution patterns and control of soil organic carbon in coastal salt
      marshes with different plant covers.
AB  - This study was carried out in three kinds of salt marshes according to the
      vegetation covers, including Phragmites australis salt marsh (PSM), Suaeda salus
      salt marsh (SSM) and Tamarix chinensis-Suaeda salus salt marsh (TSSM). We applied
      allometric function, exponential function and logistic function to model the
      depth distribution of the SOCv and SOCc for each salt marsh, respectively. The
      results showed that the exponential function fits the depth distribution of the
      SOCv more well than other two functions. The SOCc can be fitted very well by all
      three functions for three salt marsh (Adj. R2 > 0.99), of which the allometric
      function was the best one. The mean topsoil concentration factors (TCFs) of three
      salt marshes were beyond 0.1, which means the SOC enrichment in surface soils due
      to plant cycling, but TCFs in PSM were significantly higher than those in SSM (P
      < 0.05). Nearly 30% of SOC was concentrated in the top 20 cm soils. The results
      of general linear model (GLM) suggested that four soil properties (soil water
      content, pH, soil salt content and silt+clay) and their interactive effects
      explained about 80% of the total variation of SOC stock in the top 20 cm soils
      and the 20-100 cm soil layers.

PMID- 27708419
TI  - Suppression of the CD8 T cell response by human papillomavirus type 16 E7 occurs
      in Langerhans cell-depleted mice.
AB  - Human papillomavirus (HPV) is an epitheliotropic virus that is the primary causal
      agent for cervical cancer. Langerhans cells (LC) are skin antigen presenting
      cells that are reduced in number in HPV-infected skin. The aim of this study was
      to understand the immune-modulatory effects of HPV16 E7 on LC and on the CD8 T
      cell response to a skin-expressed antigen. To test this, HPV16 E7 was expressed
      in mouse skin keratinocytes with the model antigen ovalbumin (Ova). Similar to
      what is observed in HPV-infected human skin, LC numbers were significantly
      reduced in E7-expressing mouse skin. This shows that expression of the E7 protein
      alone is sufficient to mediate LC depletion. Expression of E7 with Ova in
      keratinocytes strongly suppressed the Ova-specific CD8+ T cell response in the
      skin draining lymph node. When tested in LC-ablated mice, the CD8 T cell response
      to skin-expressed Ova in control mice was not affected, nor was the T cell
      response to Ova restored in E7-expressing skin. These data indicate a role for E7
      in regulation of LC homeostasis in the skin and in suppression of antigen
      specific CD8 T cell expansion, but suggest that these two effects occur
      independent of each other.

PMID- 27708422
TI  - Identification of doublesex alleles associated with the female-limited Batesian
      mimicry polymorphism in Papilio memnon.
AB  - The female-limited Batesian mimicry polymorphism in Papilio butterflies is an
      intriguing system for investigating the mechanism of maintenance of genetic
      polymorphisms. In Papilio polytes, an autosomal region encompassing the sex
      determinant gene doublesex controls female-limited mimicry polymorphism. In the
      closely related species P. memnon, which also exhibits female-limited Batesian
      mimicry polymorphism, we identified two allelic sequences of the doublesex gene
      that corresponded exactly with the mimetic and non-mimetic female phenotypes.
      Thus, the genetic basis of the mimicry polymorphism in P. memnon is similar to
      that in P. polytes. However, the mimetic and non-mimetic alleles of the two
      species were not identical, and the divergence of alleles occurred independently
      in P. memnon and P. polytes. Different mutation-selection processes may have
      resulted in the convergent patterns of mimicry polymorphism in these Papilio
      butterflies.

PMID- 27708420
TI  - Diaphanous gene mutation affects spiral cleavage and chirality in snails.
AB  - L-R (left and right) symmetry breaking during embryogenesis and the establishment
      of asymmetric body plan are key issues in developmental biology, but the onset
      including the handedness-determining gene locus still remains unknown. Using pure
      dextral (DD) and sinistral (dd) strains of the pond snail Lymnaea stagnalis as
      well as its F2 through to F10 backcrossed lines, the single handedness
      determining-gene locus was mapped by genetic linkage analysis, BAC cloning and
      chromosome walking. We have identified the actin-related diaphanous gene Lsdia1
      as the strongest candidate. Although the cDNA and derived amino acid sequences of
      the tandemly duplicated Lsdia1 and Lsdia2 genes are very similar, we could
      discriminate the two genes/proteins in our molecular biology experiments. The
      Lsdia1 gene of the sinistral strain carries a frameshift mutation that abrogates
      full-length LsDia1 protein expression. In the dextral strain, it is already
      translated prior to oviposition. Expression of Lsdia1 (only in the dextral
      strain) and Lsdia2 (in both chirality) decreases after the 1-cell stage, with no
      asymmetric localization throughout. The evolutionary relationships among body
      handedness, SD/SI (spiral deformation/spindle inclination) at the third cleavage,
      and expression of diaphanous proteins are discussed in comparison with three
      other pond snails (L. peregra, Physa acuta and Indoplanorbis exustus).

PMID- 27708423
TI  - lncScore: alignment-free identification of long noncoding RNA from assembled
      novel transcripts.
AB  - RNA-Seq based transcriptome assembly has been widely used to identify novel
      lncRNAs. However, the best-performing transcript reconstruction methods merely
      identified 21% of full-length protein-coding transcripts from H. sapiens. Those
      partial-length protein-coding transcripts are more likely to be classified as
      lncRNAs due to their incomplete CDS, leading to higher false positive rate for
      lncRNA identification. Furthermore, potential sequencing or assembly error that
      gain or abolish stop codons also complicates ORF-based prediction of lncRNAs.
      Therefore, it remains a challenge to identify lncRNAs from the assembled
      transcripts, particularly the partial-length ones. Here, we present a novel
      alignment-free tool, lncScore, which uses a logistic regression model with 11
      carefully selected features. Compared to other state-of-the-art alignment-free
      tools (e.g. CPAT, CNCI, and PLEK), lncScore outperforms them on accurately
      distinguishing lncRNAs from mRNAs, especially partial-length mRNAs in the human
      and mouse datasets. In addition, lncScore also performed well on transcripts from
      five other species (Zebrafish, Fly, C. elegans, Rat, and Sheep). To speed up the
      prediction, multithreading is implemented within lncScore, and it only took 2
      minute to classify 64,756 transcripts and 54 seconds to train a new model with
      21,000 transcripts with 12 threads, which is much faster than other tools.
      lncScore is available at https://github.com/WGLab/lncScore.

PMID- 27708424
TI  - Aromatic and proteomic analyses corroborate the distinction between Mediterranean
      landraces and modern varieties of durum wheat.
AB  - In this paper volatile organic compounds (VOCs) from durum wheat cultivars and
      landraces were analyzed using PTR-TOF-MS. The aim was to characterize the VOC's
      profile of the wholemeal flour and of the kernel to find out if any VOCs were
      specific to varieties and sample matrices. The VOC data is accompanied by SDS
      PAGE analyses of the storage proteins (gliadins and glutenins). Statistical
      analyses was carried out both on the signals obtained by MS and on the protein
      profiles. The difference between the VOC profile of two cultivars or two
      preparations of the same sample - matrices, in this case kernel vs wholemeal
      flour - can be very subtle; the high resolution of PTR-TOF-MS - down to levels as
      low as pptv - made it possible to recognize these differences. The effects of
      grinding on the VOC profiles were analyzed using SIMPER and Tanglegram
      statistical methods. Our results show that it is possible describe samples using
      VOC profiles and protein data.

PMID- 27708425
TI  - Genetic and clinical characterization of Pakistani families with Bardet-Biedl
      syndrome extends the genetic and phenotypic spectrum.
AB  - Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder that is both
      genetically and clinically heterogeneous. To date 19 genes have been associated
      with BBS, which encode proteins active at the primary cilium, an antenna-like
      organelle that acts as the cell's signaling hub. In the current study, a
      combination of mutation screening, targeted sequencing of ciliopathy genes
      associated with BBS, and whole-exome sequencing was used for the genetic
      characterization of five families including four with classic BBS symptoms and
      one BBS-like syndrome. This resulted in the identification of novel mutations in
      BBS genes ARL6 and BBS5, and recurrent mutations in BBS9 and CEP164. In the case
      of CEP164, this is the first report of two siblings with a BBS-like syndrome with
      mutations in this gene. Mutations in this gene were previously associated with
      nephronophthisis 15, thus the current results expand the CEP164-associated
      phenotypic spectrum. The clinical and genetic spectrum of BBS and BBS-like
      phenotypes is not fully defined in Pakistan. Therefore, genetic studies are
      needed to gain insights into genotype-phenotype correlations, which will in turn
      improve the clinician's ability to make an early and accurate diagnosis, and
      facilitate genetic counseling, leading to directly benefiting families with
      affected individuals.

PMID- 27708427
TI  - Switchable thulium-doped fiber laser from polarization rotation vector to scalar
      soliton.
AB  - We experimentally demonstrate switchable temporal soliton generation from a
      thulium-doped fiber laser (TDFL), using carbon nanotubes as the mode-locker. With
      the help of residual polarization dependent loss of a wavelength division
      multiplexer, a weak nonlinear polarization rotation (NPR) effect can be achieved
      within the laser cavity, which may provide joint contribution for passive mode
      locking operation. By finely adjusting the polarization to alter the strength of
      NPR-based saturable absorption, the TDFL either approaches the operation regime
      of scalar soliton with strong NPR effect, or generates polarization rotation
      locked vector soliton (PRLVS) with weak NPR effect. The scalar solitons and
      PRLVSs possess 3-dB optical spectrum bandwidth of 2.2 nm and 2 nm, pulse-width of
      1.8 ps and 2 ps, respectively. Moreover, the PRLVSs demonstrate a typical energy
      exchange between two polarized components on optical spectra and a period
      doubling feature in time domain. Such operation principle can also be used in
      1550 nm band fiber lasers and other nonlinear systems.

PMID- 27708426
TI  - Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In
      Compacted Nucleosome Arrays.
AB  - The activation of a silent gene locus is thought to involve pioneering
      transcription factors that initiate changes in the local chromatin structure to
      increase promoter accessibility and binding of downstream effectors. To better
      understand the molecular requirements for the first steps of locus activation, we
      investigated whether acetylation of a single nucleosome is sufficient to alter
      DNA accessibility within a condensed 25-nucleosome array. We found that
      acetylation mimics within the histone H4 tail domain increased accessibility of
      the surrounding linker DNA, with the increased accessibility localized to the
      immediate vicinity of the modified nucleosome. In contrast, acetylation mimics
      within the H3 tail had little effect, but were able to synergize with H4 tail
      acetylation mimics to further increase accessibility. Moreover, replacement of
      the central nucleosome with a nucleosome free region also resulted in increased
      local, but not global DNA accessibility. Our results indicate that modification
      or disruption of only a single target nucleosome results in significant changes
      in local chromatin architecture and suggest that very localized chromatin
      modifications imparted by pioneer transcription factors are sufficient to
      initiate a cascade of events leading to promoter activation.

PMID- 27708430
TI  - Unravelling the Efficient Photocatalytic Activity of Boron-induced Ti3+ Species
      in the Surface Layer of TiO2.
AB  - Ti3+ species are highly unstable in air owing to their facile oxidation into Ti4+
      species, and thus they cannot concentrate in the surface layer of TiO2 but are
      mainly present in its bulk. We report generation of abundant and stable Ti3+
      species in the surface layer of TiO2 by boron doping for efficient utilization of
      solar irradiation. The resultant photocatalysts (denoted as B-TiO2-x) exhibit
      extremely high and stable solar-driven photocatalytic activity toward hydrogen
      production. The origin of the solar-light activity enhancement in the B-TiO2-x
      photocatalysts has been thoroughly investigated by various experimental
      techniques and density functional theory (DFT) calculations. The unique structure
      invoked by presence of sufficient interstitial boron atoms can lead to
      substantial variations in density of states of B-TiO2-x, which not only
      significantly narrow the band gap of TiO2 to improve its visible-light
      absorption, but also promote the photogenerated electron mobility to enhance its
      solar-light photocatalytic activity.

PMID- 27708429
TI  - Structural basis for PPAR partial or full activation revealed by a novel ligand
      binding mode.
AB  - The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors
      involved in the regulation of the metabolic homeostasis and therefore represent
      valuable therapeutic targets for the treatment of metabolic diseases. The
      development of more balanced drugs interacting with PPARs, devoid of the side
      effects showed by the currently marketed PPARgamma full agonists, is considered
      the major challenge for the pharmaceutical companies. Here we present a structure
      based virtual screening approach that let us identify a novel PPAR pan-agonist
      with a very attractive activity profile and its crystal structure in the complex
      with PPARalpha and PPARgamma, respectively. In PPARalpha this ligand occupies a
      new pocket whose filling is allowed by the ligand-induced switching of the F273
      side chain from a closed to an open conformation. The comparison between this
      pocket and the corresponding cavity in PPARgamma provides a rationale for the
      different activation of the ligand towards PPARalpha and PPARgamma, suggesting a
      novel basis for ligand design.

PMID- 27708428
TI  - GSF2 deletion increases lactic acid production by alleviating glucose repression
      in Saccharomyces cerevisiae.
AB  - Improving lactic acid (LA) tolerance is important for cost-effective microbial
      production of LA under acidic fermentation conditions. Previously, we generated
      LA-tolerant D-LA-producing S. cerevisiae strain JHY5310 by laboratory adaptive
      evolution of JHY5210. In this study, we performed whole genome sequencing of
      JHY5310, identifying four loss-of-function mutations in GSF2, SYN8, STM1, and
      SIF2 genes, which are responsible for the LA tolerance of JHY5310. Among the
      mutations, a nonsense mutation in GSF2 was identified as the major contributor to
      the improved LA tolerance and LA production in JHY5310. Deletion of GSF2 in the
      parental strain JHY5210 significantly improved glucose uptake and D-LA production
      levels, while derepressing glucose-repressed genes including genes involved in
      the respiratory pathway. Therefore, more efficient generation of ATP and NAD+ via
      respiration might rescue the growth defects of the LA-producing strain, where ATP
      depletion through extensive export of lactate and proton is one of major reasons
      for the impaired growth. Accordingly, alleviation of glucose repression by
      deleting MIG1 or HXK2 in JHY5210 also improved D-LA production. GSF2 deletion
      could be applied to various bioprocesses where increasing biomass yield or
      respiratory flux is desirable.

PMID- 27708431
TI  - Attenuation of synaptic toxicity and MARK4/PAR1-mediated Tau phosphorylation by
      methylene blue for Alzheimer's disease treatment.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by
      genotypic and phenotypic heterogeneity. Critical components of the two AD
      pathological pathways, Abeta-amyloidosis and Tauopathy, have been considered as
      therapeutic targets. Among them, much effort is focused on aberrant Tau
      phosphorylation and targeting Tau-phosphorylating kinases. Methylene blue (MB), a
      phenothiazine dye that crosses the blood-brain barrier, has been shown to hit
      multiple molecular targets involved in AD and have beneficial effects in clinical
      studies. Here we present evidence that microtubule affinity-regulating kinase
      (MARK4) is a novel target of MB. MB partially rescued the synaptic toxicity in
      Drosophila larva overexpressing PAR1 (MARK analog). In 293T culture, MB decreased
      MARK4-mediated Tau phosphorylation in a dose dependent manner. Further studies
      revealed a two-fold mechanism by MB including down-regulation of MARK4 protein
      level through ubiquitin-proteasome pathway and inhibition of MARK4 kinase
      activity in vitro. This study highlights the importance of MARK4 as a viable
      target for Tauopathy and provides fresh insight into the complex mechanism used
      by MB to treat AD.

PMID- 27708432
TI  - Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to
      metabolic control dysregulation.
AB  - Ketone bodies have been shown to transiently stimulate food intake and modify
      energy homeostasis regulatory systems following cerebral infusion for a moderate
      period of time (<6 hours). As ketone bodies are usually enhanced during episodes
      of fasting, this effect might correspond to a physiological regulation. In
      contrast, ketone bodies levels remain elevated for prolonged periods during
      obesity, and thus could play an important role in the development of this
      pathology. In order to understand this transition, ketone bodies were infused
      through a catheter inserted in the carotid to directly stimulate the brain for a
      period of 24 hours. Food ingested and blood circulating parameters involved in
      metabolic control as well as glucose homeostasis were determined. Results show
      that ketone bodies infusion for 24 hours increased food intake associated with a
      stimulation of hypothalamic orexigenic neuropeptides. Moreover, insulinemia was
      increased and caused a decrease in glucose production despite an increased
      resistance to insulin. The present study confirms that ketone bodies reaching the
      brain stimulates food intake. Moreover, we provide evidence that a prolonged
      hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms.
      Finally, this study shows that brain exposure to ketone bodies alters insulin
      signaling and consequently glucose homeostasis.

PMID- 27708434
TI  - Clinical Relevance and Molecular Phenotypes in Gastric Cancer, of TP53 Mutations
      and Gene Expressions, in Combination With Other Gene Mutations.
AB  - While altered TP53 is the most frequent mutation in gastric cancer (GC), its
      association with molecular or clinical phenotypes (e.g., overall survival,
      disease-free survival) remains little known. To that end, we can use genome-wide
      approaches to identify altered genes significantly related to mutated TP53. Here,
      we identified significant differences in clinical outcomes, as well as in
      molecular phenotypes, across specific GC tumor subpopulations, when combining
      TP53 with other signaling networks, including WNT and its related genes NRXN1,
      CTNNB1, SLITRK5, NCOR2, RYR1, GPR112, MLL3, MTUS2, and MYH6. Moreover, specific
      GC subpopulations indicated by dual mutation of NRXN1 and TP53 suggest different
      drug responses, according to the Connectivity Map, a pharmacological drug-gene
      association tool. Overall, TP53 mutation status in GC is significantly relevant
      to clinical or molecular categories. Thus, our approach can potentially provide a
      patient stratification strategy by dissecting previously unknown multiple TP53
      mutated patient groups.

PMID- 27708435
TI  - There is no difference in contagious yawning between men and women.

PMID- 27708433
TI  - Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human
      papillomavirus type 58.
AB  - To enable rational multi-epitope vaccine and diagnostic antigen design, it is
      imperative to delineate complete IgG-epitome of the protein. Here, we describe
      results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic
      human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing
      peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were
      mapped on E6, E7 and L1 proteins using rabbits antisera to the respective
      recombinant proteins. Using sequence alignment based on BCE minimal motif, the
      specificity and conservativeness of each mapped BCE were delineated mainly among
      known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1
      that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18
      BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like
      particles, suggesting that these are antibody accessible BCEs. Also, a highly
      conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR
      HPVs, which could be used as the first peptide reference marker for judging HR
      HPVs. Altogether, this study provides systemic and exhaustive information on
      linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope
      diagnostic reagents/chips for testing viral antibodies and 'universal' preventive
      HPV peptide vaccine based on L1 conserved BCEs.

PMID- 27708436
TI  - Ionization fraction and the enhanced sulfur chemistry in Barnard 1.
AB  - CONTEXT: Barnard B1b has revealed as one of the most interesting globules from
      the chemical and dynamical point of view. It presents a rich molecular chemistry
      characterized by large abundances of deuterated and complex molecules.
      Furthermore, it hosts an extremely young Class 0 object and one candidate to
      First Hydrostatic Core (FHSC) proving the youth of this star forming region.
      AIMS: Our aim is to determine the cosmic ray ionization rate, [Formula: see
      text], and the depletion factors in this extremely young star forming region.
      These parameteres determine the dynamical evolution of the core. METHODS: We
      carried out a spectral survey towards Barnard 1b as part of the IRAM Large
      program ASAI using the IRAM 30-m telescope at Pico Veleta (Spain). This provided
      a very complete inventory of neutral and ionic C-, N- and S- bearing species
      with, up to our knowledge, the first secure detections of the deuterated ions
      DCS+ and DOCO+. We use a state-of-the-art pseudo-time-dependent gas-phase
      chemical model that includes the ortho and para forms of [Formula: see text] and
      [Formula: see text] to determine the local value of the cosmic ray ionization
      rate and the depletion factors. RESULTS: Our model assumes n(H2)=105 cm-3 and T k
      =12 K, as derived from our previous works. The observational data are well fitted
      with zetaH2 between 3*10-17 s-1 and 10-16 s-1, and the following elemental
      abundances: O/H=3 10-5, N/H=6.4-8 10-5, C/H=1.7 10-5 and S/H between 6.0 10-7 and
      1.0 10-6. The large number of neutral/protonated species detected, allows us to
      derive the elemental abundances and cosmic ray ionization rate simultaneously.
      Elemental depletions are estimated to be ~10 for C and O, ~1 for N and ~25 for S.
      CONCLUSIONS: Barnard B1b presents similar depletions of C and O than those
      measured in pre-stellar cores. The depletion of sulfur is higher than that of C
      and O but not as extreme as in cold cores. In fact, it is similar to the values
      found in some bipolar outflows, hot cores and photon-dominated regions. Several
      scenarios are discussed to account for these peculiar abundances. We propose that
      it is the consequence of the initial conditions (important outflows and enhanced
      UV fields in the surroundings) and a rapid collapse (~0.1 Myr) that permits to
      maintain most S- and N-bearing species in gas phase to great optical depths. The
      interaction of the compact outflow associated with B1b-S with the surrounding
      material could enhance the abundances of S-bearing molecules, as well.

PMID- 27708437
TI  - Antimicrobial use in animals editorial - Comments on companion animal use and
      animal welfare.

PMID- 27708438
TI  - Antimicrobial use in animals editorial - Comments on companion animal use and
      animal welfare - A response.

PMID- 27708439
TI  - Irradiation of ground beef.

PMID- 27708440
TI  - Ethical question of the month - October 2016.

PMID- 27708441
TI  - Squamous cell carcinoma causing dorsal atlantoaxial spinal cord compression in a
      dog.
AB  - A 12-year-old Chihuahua dog was presented for cervical pain and progressive
      tetraparesis. Magnetic resonance imaging revealed spinal cord compression due to
      a mass in the dorsal atlantoaxial region. Surgical treatment was performed. The
      mass was histopathologically diagnosed as a squamous cell carcinoma. The dog
      recovered to normal neurologic status after surgery.

PMID- 27708442
TI  - Perineal evisceration secondary to a bite injury in a dog with an untreated
      perineal hernia.
AB  - Emergency surgery was performed on a 6-year-old castrated male springer spaniel
      dog with evisceration of most of the small intestinal tract through the perineal
      region, secondary to a dog attack. This is the first report describing successful
      treatment of perineal evisceration secondary to dog attack at an untreated
      perineal hernia, employing abdominal and perineal approaches.

PMID- 27708443
TI  - Fournier's gangrene associated with chronic kidney disease in a dog.
AB  - A dog was diagnosed with Fournier's gangrene associated with chronic kidney
      disease. Clinical features included crepitant scrotal inflammation that spread to
      the penis; the lesion exhibited liquefactive necrosis or purulent moist gangrene.
      This is the first description of Fournier's gangrene associated with chronic
      kidney disease in a dog.

PMID- 27708444
TI  - Is Corynebacterium pseudotuberculosis infection (pigeon fever) in horses an
      emerging disease in western Canada?
AB  - This report describes 5 horses in the southern Alberta region with typical and
      atypical external abscessation due to Corynebacterium pseudotuberculosis (pigeon
      fever). "Pigeon fever" has recently been diagnosed in new geographic regions in
      North America and should be kept as a differential diagnosis by practitioners
      when an external or internal abscess is identified in a horse.

PMID- 27708445
TI  - Acute myeloid leukemia with basophilic differentiation in a 3-year-old
      Standardbred gelding.
AB  - A 3-year-old Standardbred gelding with a history of pyrexia, persistent
      hemorrhage from the oral cavity, and a large, soft swelling at the junction of
      the caudal aspect of the mandibular rami and proximal neck was evaluated. The
      horse had neutropenia and anemia, with atypical granulated cells in a blood
      smear. Additional tests confirmed acute myeloid leukemia with basophilic
      differentiation, which has been reported in humans, cats, dogs, and cattle but
      not horses.

PMID- 27708446
TI  - Mesenteric thrombus associated with pulmonary, splenic, portal, and caval thrombi
      in a dog that was presented for an acute abdomen.
AB  - A 6-year-old Labrador retriever dog was presented for acute abdominal pain. A
      tentative diagnosis of mesenteric thrombosis was established antemortem. The dog
      was treated with supportive care and anti-coagulation but was ultimately
      euthanized due to disease-related complications. Necropsy examination confirmed
      an acute mesenteric thrombus along with widespread thromboembolic disease.
      Potential causes were protein-losing nephropathy, hepatopathy, and/or
      corticosteroid administration.

PMID- 27708447
TI  - Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with
      an adrenal cortical carcinoma.
AB  - A 14-year-old neutered male domestic shorthaired cat was diagnosed with an
      adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary
      hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy
      were performed. Adrenal cortical neoplasia should be ruled out in any neutered
      male cat with mammary development and/or exhibiting sexual behavior.

PMID- 27708448
TI  - Diagnostic value of creatine kinase activity in canine cerebrospinal fluid.
AB  - This study aimed to determine whether creatine kinase (CK) activity in
      cerebrospinal fluid (CSF) has diagnostic value for various groups of neurological
      conditions or for different anatomical areas of the nervous system (NS). The age,
      breed, results of CSF analysis, and diagnosis of 578 canine patients presenting
      with various neurological conditions between January 2009 and February 2015 were
      retrospectively collected. The cases were divided according to anatomical areas
      of the nervous system, i.e., brain, spinal cord, and peripheral nervous system,
      and into groups according to the nature of the condition diagnosed: vascular,
      immune/inflammatory/infectious, traumatic, toxic, anomalous, metabolic,
      idiopathic, neoplastic, and degenerative. Statistical analysis showed that CSF-CK
      alone cannot be used as a diagnostic tool and that total proteins in the CSF and
      red blood cells (RBCs) do not have a significant relationship with the CSF-CK
      activity. CSF-CK did not have a diagnostic value for different disease groups or
      anatomical areas of the nervous system.

PMID- 27708450
TI  - Wildlife health: A foundation for preparedness for environmental change.

PMID- 27708449
TI  - Simultaneous staphylectomy and unilateral arytenoid lateralization in dogs
      presenting for dyspnea: 23 cases (2010-2013).
AB  - This retrospective study assesses postoperative complications with simultaneous
      staphylectomy and unilateral arytenoid lateralization (SP + UAL) in dogs with
      laryngeal paralysis and concurrent elongation of the soft palate compared to dogs
      having a UAL alone. Medical records of dogs having a UAL performed from 2010 to
      2013 were reviewed. Twenty-three dogs were diagnosed with a concurrent elongated
      soft palate and had a SP + UAL performed and 89 dogs were diagnosed with an
      appropriate soft palate and had only a UAL performed. A telephone questionnaire
      for long-term postoperative outcomes was completed. Survival probability was not
      statistically different between the 2 groups. Dogs in the SP + UAL group were
      more likely to be seen for respiratory distress after surgery (P = 0.05). There
      was no significant difference between the 2 groups in the number of dogs which
      developed postoperative aspiration pneumonia. The overall complication rate for
      both groups was high, with postoperative pneumonia being the most common
      complication.

PMID- 27708451
TI  - A perspective from 10 years of practice.

PMID- 27708452
TI  - Emerging SAESA communication challenges.

PMID- 27708453
TI  - Affective Reading: Chaucer, Women and Romance.

PMID- 27708454
TI  - Assessing the effects of repeated handling on the physiology and condition of
      semi-precocial nestlings.
AB  - Repeated exposure to elevated levels of glucocorticoids during development can
      have long-term detrimental effects on survival and fitness, potentially
      associated with increased telomere attrition. Nestling birds are regularly
      handled for ecological research, yet few authors have considered the potential
      for handling-induced stress to influence hormonally mediated phenotypic
      development or bias interpretations of subsequent focal measurements. We
      experimentally manipulated the handling experience of the semi-precocial
      nestlings of European Storm Petrel Hydrobates pelagicus to simulate handling in a
      typical field study and examined cumulative effects on physiology and condition
      in late postnatal development. Neither baseline corticosterone (the primary
      glucocorticoid in birds), telomere length nor body condition varied with the
      number of handling episodes. The absence of a response could be explained if
      Storm Petrels did not perceive handling to be stressful or if there is
      dissociation of the hypothalamic-pituitary-adrenal axis from stressful stimuli in
      early life. Eliciting a response to a stressor may be maladaptive for cavity
      dwelling young that are unable to escape or defend themselves. Furthermore,
      avoiding elevated overall glucocorticoid exposure may be particularly important
      in a long-lived species, in which accelerated early-life telomere erosion could
      impact negatively upon longevity. We propose that the level of colony-wide
      disturbance induced by investigator handling of young could be important in
      underlining species-specific responses. Storm Petrel nestlings appear
      unresponsive to investigator handling within the limits of handling in a typical
      field study and handling at this level should not bias physiological and
      morphological measurements.

PMID- 27708455
TI  - Regional surnames and genetic structure in Great Britain.
AB  - Following the increasing availability of DNA-sequenced data, the genetic
      structure of populations can now be inferred and studied in unprecedented detail.
      Across social science, this innovation is shaping new bio-social research
      agendas, attracting substantial investment in the collection of genetic,
      biological and social data for large population samples. Yet genetic samples are
      special because the precise populations that they represent are uncertain and ill
      defined. Unlike most social surveys, a genetic sample's representativeness of the
      population cannot be established by conventional procedures of statistical
      inference, and the implications for population-wide generalisations about bio
      social phenomena are little understood. In this paper, we seek to address these
      problems by linking surname data to a censored and geographically uneven sample
      of DNA scans, collected for the People of the British Isles study. Based on a
      combination of global and local spatial correspondence measures, we identify
      eight regions in Great Britain that are most likely to represent the geography of
      genetic structure of Great Britain's long-settled population. We discuss the
      implications of this regionalisation for bio-social investigations. We conclude
      that, as the often highly selective collection of DNA and biomarkers becomes a
      more common practice, geography is crucial to understanding variation in genetic
      information within diverse populations.

PMID- 27708456
TI  - The importance of realistic dispersal models in conservation planning:
      application of a novel modelling platform to evaluate management scenarios in an
      Afrotropical biodiversity hotspot.
AB  - As biodiversity hotspots are often characterized by high human population
      densities, implementation of conservation management practices that focus only on
      the protection and enlargement of pristine habitats is potentially unrealistic.
      An alternative approach to curb species extinction risk involves improving
      connectivity among existing habitat patches. However, evaluation of spatially
      explicit management strategies is challenging, as predictive models must account
      for the process of dispersal, which is difficult in terms of both empirical data
      collection and modelling.Here, we use a novel, individual-based modelling
      platform that couples demographic and mechanistic dispersal models to evaluate
      the effectiveness of realistic management scenarios tailored to conserve forest
      birds in a highly fragmented biodiversity hotspot. Scenario performance is
      evaluated based on the spatial population dynamics of a well-studied forest bird
      species.The largest population increase was predicted to occur under scenarios
      increasing habitat area. However, the effectiveness was sensitive to spatial
      planning. Compared to adding one large patch to the habitat network, adding
      several small patches yielded mixed benefits: although overall population sizes
      increased, specific newly created patches acted as dispersal sinks, which
      compromised population persistence in some existing patches. Increasing matrix
      connectivity by the creation of stepping stones is likely to result in enhanced
      dispersal success and occupancy of smaller patches. Synthesis and applications.
      We show that the effectiveness of spatial management is strongly driven by
      patterns of individual dispersal across landscapes. For species conservation
      planning, we advocate the use of models that incorporate adequate realism in
      demography and, particularly, in dispersal behaviours.

PMID- 27708457
TI  - Type of fitness cost influences the rate of evolution of resistance to transgenic
      Bt crops.
AB  - The evolution of resistance to pesticides by insect pests is a significant
      challenge for sustainable agriculture. For transgenic crops expressing Bacillus
      thuringiensis (Bt), crystalline (Cry) toxins resistance evolution may be delayed
      by the high-dose/refuge strategy in which a non-toxic refuge is planted to
      promote the survival of susceptible insects. The high-dose/refuge strategy may
      interact with fitness costs associated with resistance alleles to further delay
      resistance. However, while a diverse range of fitness costs are reported in the
      field, they are typically represented as a fixed reduction in survival or
      viability which is insensitive to ecological conditions such as competition.
      Furthermore, the potential dynamic consequences of restricting susceptible
      insects to a refuge which represents only a fraction of the available space have
      rarely been considered.We present a generalized discrete time model which
      utilizes dynamic programming methods to derive the optimal management decisions
      for the control of a theoretical insect pest population exposed to Bt crops. We
      consider three genotypes (susceptible homozygotes, resistant homozygotes and
      heterozygotes) and implement fitness costs of resistance to Bt toxins as either a
      decrease in the relative competitive ability of resistant insects or as a penalty
      on fecundity. Model analysis is repeated and contrasted for two types of density
      dependence: uniform density dependence which operates equally across the
      landscape and heterogeneous density dependence where the intensity of competition
      scales inversely with patch size and is determined separately for the refuge and
      Bt crop.When the planting of Bt is decided optimally, fitness costs to fecundity
      allow for the planting of larger areas of Bt crops than equivalent fitness costs
      that reduce the competitive ability of resistant insects.Heterogeneous
      competition only influenced model predictions when the proportional area of Bt
      planted in each season was decided optimally and resistance was not recessive.
      Synthesis and applications. The high-dose/refuge strategy alone is insufficient
      to preserve susceptibility to transgenic Bacillus thuringiensis (Bt) crops in the
      long term when constraints upon the evolution of resistance are not
      insurmountable. Fitness costs may enhance the delaying effect of the refuge, but
      the extent to which they do so depends upon how the cost is realized
      biologically. Fitness costs which apply independently of other variables may be
      more beneficial to resistance management than costs which are only visible to
      selection under a limited range of ecological conditions.

PMID- 27708458
TI  - RAFT Dispersion Alternating Copolymerization of Styrene with N-Phenylmaleimide:
      Morphology Control and Application as an Aqueous Foam Stabilizer.
AB  - We report a new nonaqueous polymerization-induced self-assembly (PISA)
      formulation based on the reversible addition-fragmentation chain transfer (RAFT)
      dispersion alternating copolymerization of styrene with N-phenylmaleimide using a
      nonionic poly(N,N-dimethylacrylamide) stabilizer in a 50/50 w/w ethanol/methyl
      ethyl ketone (MEK) mixture. The MEK cosolvent is significantly less toxic than
      the 1,4-dioxane cosolvent reported previously [Yang P.; Macromolecules2013, 46,
      8545-8556]. The core-forming alternating copolymer block has a relatively high
      glass transition temperature (Tg), which leads to vesicular morphologies being
      observed during PISA, as well as the more typical sphere and worm phases. Each of
      these copolymer morphologies has been characterized by transmission electron
      microscopy (TEM) and small-angle X-ray scattering (SAXS) studies. TEM studies
      reveal micrometer-sized elliptical particles with internal structure, with SAXS
      analysis suggesting an oligolamellar vesicle morphology. This structure differs
      from that previously reported for a closely related PISA formulation utilizing a
      poly(methacrylic acid) stabilizer block for which unilamellar platelet-like
      particles are observed by TEM and SAXS. This suggests that interlamellar
      interactions are governed by the nature of the steric stabilizer layer. Moreover,
      using the MEK cosolvent also enables access to a unilamellar vesicular
      morphology, despite the high Tg of the alternating copolymer core-forming block.
      This was achieved by simply conducting the PISA synthesis at a higher temperature
      for a longer reaction time (80  degrees C for 24 h). Presumably, MEK solvates the
      core-forming block more than the previously utilized 1,4-dioxane cosolvent, which
      leads to greater chain mobility. Finally, preliminary experiments indicate that
      the worms are much more efficient stabilizers for aqueous foams than either the
      spheres or the oligolamellar elliptical vesicles.

PMID- 27708459
TI  - Dose and number of applications that maximize fungicide effective life
      exemplified by Zymoseptoria tritici on wheat - a model analysis.
AB  - Two key decisions that need to be taken about a fungicide treatment programme are
      (i) the number of applications that should be used per crop growing season, and
      (ii) the dosage that should be used in each application. There are two opposing
      considerations, with control efficacy improved by a higher number of applications
      and higher dose, and resistance management improved by a lower number of
      applications and lower dose. Resistance management aims to prolong the effective
      life of the fungicide, defined as the time between its introduction onto the
      market for use on the target pathogen, and the moment when effective control is
      lost due to a build-up of fungicide resistance. Thus, the question is whether
      there are optimal combinations of dose rate and number of applications that both
      provide effective control and lead to a longer effective life. In this paper, it
      is shown how a range of spray programmes can be compared and optimal programmes
      selected. This is explored with Zymoseptoria tritici on wheat and a quinone
      outside inhibitor (QoI) fungicide. For this pathogen-fungicide combination, a
      single treatment provided effective control under the simulated disease pressure,
      but only if the application timing was optimal and the dose was close to the
      maximum permitted. Programmes with three applications were generally not optimal
      as they exerted too much selection for resistance. Two-application fungicide
      programmes balanced effective control with reasonable flexibility of dose and
      application timing, and low resistance selection, leading to long effective lives
      of the fungicide.

PMID- 27708460
TI  - Respectability, morality and disgust in the night-time economy: exploring
      reactions to 'lap dance' clubs in England and Wales.
AB  - The night-time economy is often described as repelling consumers fearful of the
      'undesirable Others' imagined dominant within such time-spaces. In this paper we
      explore this by describing attitudes towards, and reactions to, one particularly
      contentious site: the 'lap dance' club. Often targeted by campaigners in England
      and Wales as a source of criminality and anti-sociality, in this paper we shift
      the focus from fear to disgust, and argue that Sexual Entertainment Venues (SEVs)
      are opposed on the basis of moral judgments that reflect distinctions of both
      class and gender. Drawing on documentary analysis, survey results and interview
      data collected during guided walks, we detail the concerns voiced by those
      anxious about the presence of lap dance or striptease clubs in their town or
      city, particularly the notion that they 'lower the tone' of particular streets or
      neighbourhoods. Our conclusion is that the opposition expressed to lap dance
      clubs is part of an attempt to police the boundaries of respectable masculinities
      and femininities, marginalizing the producers and consumers of sexual
      entertainment through 'speech acts' which identify such entertainment as unruly,
      vulgar and uncivilized. These findings are considered in the light of ongoing
      debates concerning the relations of morality, respectability and disgust.

PMID- 27708461
TI  - Ethical boundary-work in the animal research laboratory.
AB  - The use of animals in scientific experiments continues to attract significant
      controversy, particularly in the UK. This article draws on in-depth interviews
      with senior laboratory scientists who use animals in their research. A key claim
      is that animal research is necessary for medical advance. However, this
      promissory discourse relies on the construction of three boundaries. The first is
      between humans and non-human animals. The second is between the positive and less
      positive impacts of Home Office regulation. The third is between the use of
      animals in medicine versus other domains such as farming. The article analyses
      these discourses and evaluates the applicability of 'ethical boundary-work'
      (Wainwright et al., 2006a). I conclude that the concept is a potentially useful
      device for foregrounding ethics but argue that it carries several dangers for
      sociologists interested in claim-making in areas of controversy.

PMID- 27708462
TI  - Antileukemic alpha-pyrone derivatives from the endophytic fungus Alternaria
      phragmospora.
AB  - Four new (1-4) and two known (5 and 6) alpha-pyrone derivatives have been
      isolated from Alternaria phragmospora, an endophytic fungus from Vinca rosea,
      leaves. The isolated compounds were chemically identified to be 5-butyl-4-methoxy
      6-methyl-2H-pyran-2-one (1), 5-butyl-6-(hydroxymethyl)-4-methoxy-2H-pyran-2-one
      (2), 5-(1-hydroxybutyl)-4-methoxy-6-methyl-2H-pyran-2-one (3), 4-methoxy-6-methyl
      5-(3-oxobutyl)-2H-pyran-2-one (4), 5-(2-hydroxyethyl)-4-methoxy-6-methyl-2H-pyran
      2-one (5), and 5-[(2E)-but-2-en-1-yl]-4-methoxy-6-methyl-2H-pyran-2-one (6).
      Compounds 2 and 4 showed moderate antileukemic activities against HL60 cells with
      IC50 values of 2.2 and 0.9 MUM and against K562 cells with IC50 values of 4.5 and
      1.5 MUM, respectively.

PMID- 27708463
TI  - In this month's Bulletin.

PMID- 27708464
TI  - Stroke: a global response is needed.

PMID- 27708465
TI  - Rabies vaccine stockpile: fixing the supply chain.

PMID- 27708466
TI  - Public health round-up.

PMID- 27708467
TI  - United Nations meeting on antimicrobial resistance.
AB  - World leaders gather at the United Nations General Assembly in New York this
      month to mount a response to the growing threat of antimicrobial resistance. Gary
      Humphreys and Fiona Fleck report.

PMID- 27708468
TI  - The challenges of introducing a malaria vaccine.
AB  - For the first time a malaria vaccine is to be tested for possible inclusion in
      national immunization programmes. Malcolm Molyneux tells Fiona Fleck why
      governments may need to work hard to convince people of its benefits.

PMID- 27708469
TI  - Inpatient management of children with severe acute malnutrition: a review of WHO
      guidelines.
AB  - OBJECTIVE: To understand how the World Health Organization's (WHO's) guidelines
      on the inpatient care of children with complicated severe acute malnutrition may
      be strengthened to improve outcomes. METHODS: In December 2015, we searched
      Google scholar and WHO's website for WHO recommendations on severe acute
      malnutrition management and evaluated the history and cited evidence behind these
      recommendations. We systematically searched WHO International Clinical Trials
      Registry Platform, clinicaltrials.gov and the Controlled Trials metaRegister
      until 10 August 2015 for recently completed, ongoing, or pending trials.
      FINDINGS: WHO's guidelines provide 33 recommendations on the topic. However, 16
      (48.5%) of these recommendations were based solely on expert opinion -
      unsupported by published evidence. Another 11 (33.3%) of the recommendations were
      supported by the results of directly relevant research - i.e. either randomized
      trials (8) or observational studies (3). The other six recommendations (18.2%)
      were based on studies that were not conducted among children with complicated
      severe malnutrition or studies of treatment that were not identical to the
      recommended intervention. Trials registries included 20 studies related to the
      topic, including nine trials of alternative feeding regimens. Acute medical
      management and follow-up care studies were minimally represented. CONCLUSION:
      WHO's guidelines on the topic have a weak evidence base and have undergone
      limited substantive adjustments over the past decades. More trials are needed to
      make that evidence base more robust. If the mortality associated with severe
      malnutrition is to be reduced, inpatient and post-discharge management trials,
      supported by studies on the causes of mortality, are needed.

PMID- 27708471
TI  - Gang truce for violence prevention, El Salvador.
AB  - OBJECTIVE: To estimate the effects on homicide rates of the gang truce that was
      brokered in El Salvador in 2012. METHODS: Mathematical models based on municipal
      level census, crime and gang-intelligence data were used to estimate the effect
      of the truce on homicide rates. One model estimated the overall effect after
      accounting for the linear trend and seasonality in the homicide rate. In a
      moderated-effect model, we investigated the relationship between the truce effect
      and the numbers of MS13 (Mara Salvatrucha 13) and Eighteenth-Street gang members
      imprisoned per 100 000 population. We then ran each of these two models with
      additional control variables. We compared values before the truce - 1 January
      2010 to 29 February 2012 - with those after the truce - 1 March 2012 to 31
      December 2013. FINDINGS: The overall-effect models with and without additional
      control variables indicated a homicide rate after the truce that was
      significantly lower than the value before the truce, giving rate ratios of 0.55
      (95% confidence interval, CI: 0.49-0.63) and 0.61 (95% CI: 0.54-0.69),
      respectively. For any given municipality, the effectiveness of the truce appeared
      to increase as the number of MS13 gang members imprisoned per 100 000 population
      increased. We did not observe the same significant relationship for imprisoned
      Eighteenth-Street gang members. CONCLUSION: In the 22 months following the
      establishment of a national gang truce, the homicide rate was about 40% lower
      than in the preceding 26 months. The truce's impact appeared particularly strong
      in municipalities with relatively high numbers of imprisoned MS13 gang members
      per 100 000 population.

PMID- 27708470
TI  - Visual health screening by schoolteachers in remote communities of Peru:
      implementation research.
AB  - OBJECTIVE: To describe the adaptation and scaling-up of an intervention to
      improve the visual health of children in the Apurimac region, Peru. METHODS: In a
      pilot screening programme in 2009-2010, 26 schoolteachers were trained to detect
      and refer visual acuity problems in schoolchildren in one district in Apurimac.
      To scale-up the intervention, lessons learnt from the pilot were used to design
      strategies for: (i) strengthening multisector partnerships; (ii) promoting the
      engagement and participation of teachers and (iii) increasing children's
      attendance at referral eye clinics. Implementation began in February 2015 in two
      out of eight provinces of Apurimac, including hard-to-reach communities. We made
      an observational study of the processes and outcomes of adapting and scaling-up
      the intervention. Qualitative and quantitative analyses were made of data
      collected from March 2015 to January 2016 from programme documents, routine
      reports and structured evaluation questionnaires completed by teachers. FINDINGS:
      Partnerships were expanded after sharing the results of the pilot phase. Training
      was completed by 355 teachers and directors in both provinces, belonging to 315
      schools distributed in 24 districts. Teachers' appraisal of the training achieved
      high positive scores. Outreach eye clinics and subsidies for glasses were
      provided for poorer families. Data from six districts showed that attendance at
      the eye clinic increased from 66% (45/68 children referred) in the pilot phase to
      92% (237/259) in the implementation phase. CONCLUSION: Adaptation to the local
      context allowed the scaling-up of an intervention to improve visual health in
      children and enhanced the equity of the programme.

PMID- 27708472
TI  - A retrospective analysis of oral cholera vaccine use, disease severity and deaths
      during an outbreak in South Sudan.
AB  - OBJECTIVE: To determine whether pre-emptive oral cholera vaccination reduces
      disease severity and mortality in people who develop cholera disease during an
      outbreak. METHODS: The study involved a retrospective analysis of demographic and
      clinical data from 41 cholera treatment facilities in South Sudan on patients who
      developed cholera disease between 23 April and 20 July 2014 during a large
      outbreak, a few months after a pre-emptive oral vaccination campaign. Patients
      who developed severe dehydration were regarded as having a severe cholera
      infection. Vaccinated and unvaccinated patients were compared and multivariate
      logistic regression analysis was used to identify factors associated with
      developing severe disease or death. FINDINGS: In total, 4115 cholera patients
      were treated at the 41 facilities: 1946 (47.3%) had severe disease and 62 (1.5%)
      deaths occurred. Multivariate analysis showed that patients who received two
      doses of oral cholera vaccine were 4.5-fold less likely to develop severe disease
      than unvaccinated patients (adjusted odds ratio, aOR: 0.22; 95% confidence
      interval, CI: 0.11-0.44). Moreover, those with severe cholera were significantly
      more likely to die than those without (aOR: 4.76; 95% CI: 2.33-9.77). CONCLUSION:
      Pre-emptive vaccination with two doses of oral cholera vaccine was associated
      with a significant reduction in the likelihood of developing severe cholera
      disease during an outbreak in South Sudan. Moreover, severe disease was the
      strongest predictor of death. Two doses of oral cholera vaccine should be used in
      emergencies to reduce the disease burden.

PMID- 27708473
TI  - Zika: the origin and spread of a mosquito-borne virus.
AB  - OBJECTIVE: To describe the temporal and geographical distribution of Zika virus
      infection and associated neurological disorders, from 1947 to 1 February 2016,
      when Zika became a Public Health Emergency of International Concern (PHEIC).
      METHODS: We did a literature search using the terms "Zika" and "ZIKV" in PubMed,
      cross-checked the findings for completeness against other published reviews and
      added formal notifications to WHO submitted under the International Health
      Regulations. FINDINGS: From the discovery of Zika virus in Uganda in 1947 to the
      declaration of a PHEIC by the World Health Organization (WHO) on 1 February 2016,
      a total of 74 countries and territories had reported human Zika virus infections.
      The timeline in this paper charts the discovery of the virus (1947), its
      isolation from mosquitos (1948), the first human infection (1952), the initial
      spread of infection from Asia to a Pacific island (2007), the first known
      instance of sexual transmission (2008), reports of Guillain-Barre syndrome (2014)
      and microcephaly (2015) linked to Zika infections and the first appearance of
      Zika in the Americas (from 2015). CONCLUSION: Zika virus infection in humans
      appears to have changed in character as its geographical range has expanded from
      equatorial Africa and Asia. The change is from an endemic, mosquito-borne
      infection causing mild illness to one that can cause large outbreaks linked with
      neurological sequelae and congenital abnormalities.

PMID- 27708474
TI  - The International Finance Facility for Immunisation: stakeholders' perspectives.
AB  - OBJECTIVE: To evaluate stakeholders' understanding and opinions of the
      International Finance Facility for Immunisation (IFFIm); to identify factors
      affecting funding levels; and to explore the future use of IFFIm. METHODS:
      Between July and September 2015, we interviewed 33 individuals from 25
      organizations identified as stakeholders in IFFIm. In total 22.5 hours of semi
      structured interviews were recorded, transcribed and analysed using a framework
      method. FINDINGS: Stakeholders' understanding of IFFIm's financing mechanism and
      its outcomes varied and many stakeholders wanted more information. Participants
      highlighted that the change in the macro-economic environment following the 2008
      financial crisis affected national policy in donor countries and subsequently the
      number of new commitments IFFIm received. Since Gavi is now seen as a successful
      and mature organization, participants stated that donors prefer to donate
      directly to Gavi. The pharmaceutical industry valued IFFIm for providing funding
      stability and flexibility. Other stakeholders valued IFFIm's ability to access
      funds early and enable Gavi to increase vaccine coverage. Overall, stakeholders
      thought IFFIm was successful, but they had divergent views about IFFIm's on-going
      role. Participants listed two issues where bond financing mechanisms may be
      suitable: emergency preparedness and outcome-based time-limited interventions.
      CONCLUSION: The benefit of pledging funds through IFFIm needs to be re-evaluated.
      There are potential uses for bond financing to raise funds for other global
      health issues, but these must be carefully considered against criteria to
      establish effectiveness, with quantifiable pre-defined outcome indicators to
      evaluate performance.

PMID- 27708476
TI  - Detecting Guillain-Barre syndrome caused by Zika virus using systems developed
      for polio surveillance.

PMID- 27708475
TI  - Group-based microfinance for collective empowerment: a systematic review of
      health impacts.
AB  - OBJECTIVE: To assess the impact on health-related outcomes, of group microfinance
      schemes based on collective empowerment. METHODS: We searched the databases
      Social Sciences Citation Index, Embase, MEDLINE, MEDLINE In-Process, PsycINFO,
      Social Policy & Practice and Conference Proceedings Citation Index for articles
      published between 1 January 1980 and 29 February 2016. Articles reporting on
      health impacts associated with group-based microfinance were included in a
      narrative synthesis. FINDINGS: We identified one cluster-randomized control trial
      and 22 quasi-experimental studies. All of the included interventions targeted
      poor women living in low- or middle-income countries. Some included a health
      promotion component. The results of the higher quality studies indicated an
      association between membership of a microfinance scheme and improvements in the
      health of women and their children. The observed improvements included reduced
      maternal and infant mortality, better sexual health and, in some cases, lower
      levels of interpersonal violence. According to the results of the few studies in
      which changes in empowerment were measured, membership of the relatively large
      and well-established microfinance schemes generally led to increased empowerment
      but this did not necessarily translate into improved health outcomes. Qualitative
      evidence suggested that increased empowerment may have contributed to observed
      improvements in contraceptive use and mental well-being and reductions in the
      risk of violence from an intimate partner. CONCLUSION: Membership of the larger,
      well-established group-based microfinance schemes is associated with improvements
      in some health outcomes. Future studies need to be designed to cope better with
      bias and to assess negative as well as positive social and health impacts.

PMID- 27708478
TI  - Soil acidification and the importance of liming agricultural soils with
      particular reference to the United Kingdom.
AB  - Soil acidification is caused by a number of factors including acidic
      precipitation and the deposition from the atmosphere of acidifying gases or
      particles, such as sulphur dioxide, ammonia and nitric acid. The most important
      causes of soil acidification on agricultural land, however, are the application
      of ammonium-based fertilizers and urea, elemental S fertilizer and the growth of
      legumes. Acidification causes the loss of base cations, an increase in aluminium
      saturation and a decline in crop yields; severe acidification can cause
      nonreversible clay mineral dissolution and a reduction in cation exchange
      capacity, accompanied by structural deterioration. Soil acidity is ameliorated by
      applying lime or other acid-neutralizing materials. 'Liming' also reduces N2O
      emissions, but this is more than offset by CO 2 emissions from the lime as it
      neutralizes acidity. Because crop plants vary in their tolerance to acidity and
      plant nutrients have different optimal pH ranges, target soil pH values in the UK
      are set at 6.5 (5.8 in peaty soils) for cropped land and 6.0 (5.3 in peaty soils)
      for grassland. Agricultural lime products can be sold as 'EC Fertiliser Liming
      Materials' but, although vital for soil quality and agricultural production,
      liming tends to be strongly influenced by the economics of farming. Consequently,
      much less lime is being applied in the UK than required, and many arable and
      grassland soils are below optimum pH.

PMID- 27708477
TI  - Assessment of a numerical model to reproduce event-scale erosion and deposition
      distributions in a braided river.
AB  - Numerical morphological modeling of braided rivers, using a physics-based
      approach, is increasingly used as a technique to explore controls on river
      pattern and, from an applied perspective, to simulate the impact of channel
      modifications. This paper assesses a depth-averaged nonuniform sediment model
      (Delft3D) to predict the morphodynamics of a 2.5 km long reach of the braided
      Rees River, New Zealand, during a single high-flow event. Evaluation of model
      performance primarily focused upon using high-resolution Digital Elevation Models
      (DEMs) of Difference, derived from a fusion of terrestrial laser scanning and
      optical empirical bathymetric mapping, to compare observed and predicted patterns
      of erosion and deposition and reach-scale sediment budgets. For the calibrated
      model, this was supplemented with planform metrics (e.g., braiding intensity).
      Extensive sensitivity analysis of model functions and parameters was executed,
      including consideration of numerical scheme for bed load component calculations,
      hydraulics, bed composition, bed load transport and bed slope effects, bank
      erosion, and frequency of calculations. Total predicted volumes of erosion and
      deposition corresponded well to those observed. The difference between predicted
      and observed volumes of erosion was less than the factor of two that
      characterizes the accuracy of the Gaeuman et al. bed load transport formula.
      Grain size distributions were best represented using two phi intervals. For
      unsteady flows, results were sensitive to the morphological time scale factor.
      The approach of comparing observed and predicted morphological sediment budgets
      shows the value of using natural experiment data sets for model testing.
      Sensitivity results are transferable to guide Delft3D applications to other
      rivers.

PMID- 27708479
TI  - Predictors of shell size in long-lived lake gastropods.
AB  - AIM: To investigate shell size variation among gastropod faunas of fossil and
      recent long-lived European lakes and discuss potential underlying processes.
      LOCATION: Twenty-three long-lived lakes of the Miocene to Recent of Europe.
      METHODS: Based on a dataset of 1412 species of both fossil and extant lacustrine
      gastropods, we assessed differences in shell size in terms of characteristics of
      the faunas (species richness, degree of endemism, differences in family
      composition) and the lakes (surface area, latitude and longitude of lake
      centroid, distance to closest neighbouring lake) using multiple and linear
      regression models. Because of a strong species-area relationship, we used
      resampling to determine whether any observed correlation is driven by that
      relationship. RESULTS: The regression models indicated size range expansion
      rather than unidirectional increase or decrease as the dominant pattern of size
      evolution. The multiple regression models for size range and maximum and minimum
      size were statistically significant, while the model with mean size was not.
      Individual contributions and linear regressions indicated species richness and
      lake surface area as best predictors for size changes. Resampling analysis
      revealed no significant effects of species richness on the observed patterns. The
      correlations are comparable across families of different size classes, suggesting
      a general pattern. MAIN CONCLUSIONS: Among the chosen variables, species richness
      and lake surface area are the most robust predictors of shell size in long-lived
      lake gastropods. Although the most outstanding and attractive examples for size
      evolution in lacustrine gastropods come from lakes with extensive durations,
      shell size appears to be independent of the duration of the lake as well as
      longevity of a species. The analogue of long-lived lakes as 'evolutionary
      islands' does not hold for developments of shell size because different sets of
      parameters predict size changes.

PMID- 27708480
TI  - Roads and bats: a meta-analysis and review of the evidence on vehicle collisions
      and barrier effects.
AB  - Roads are a potential threat to bat conservation. In addition to the direct risk
      of collision of bats with vehicles, roads could pose a threat to bat populations
      as a result of habitat loss, degradation and fragmentation, and could act as
      barriers to movements of bats between habitats.We performed a systematic review
      of the literature and conducted meta-analyses to assess the threat posed by roads
      to bats as a result of 1) collisions between bats and vehicles and 2) roads
      acting as barriers to movements of bats.Based on collated records of 1207 bat
      road casualties in Europe, we found that low-flying species are more prone to
      collisions than high-flying species, and that juveniles are more vulnerable to
      collisions than adults. In addition, meta-analysis identified a significant bias
      towards male casualties. Casualties included rare species such as Barbastella
      barbastellus and geographically restricted species such as Rhinolophus
      species.The bias towards male casualties could be indicative of greater natal
      philopatry or lower dispersal among females, or of sexual segregation in habitats
      of varying quality, i.e. females may occupy better quality habitats than males,
      and road density may be lower in better quality habitats.Whether or not roads act
      as barriers to the movement of bats depends on a complex interplay of habitat and
      species-specific behaviour. For example, the presence of favourable habitat for
      bats - notably woodland - was found in this review to be linked with
      significantly reduced barrier effects but a heightened risk of collision.Our data
      suggest that roads do pose a threat to bats. Future research should assess the
      contribution of traffic noise and street lighting to the barrier effect of roads.
      Where new road schemes are monitored by ecological practitioners, it is vital
      that consistent protocols are employed to ensure that bat activity can be
      compared before and after the road is built. Evidence from such research should
      be used to minimize the risks for bats of any roads built in the future, and to
      design safe crossing points for bats.

PMID- 27708481
TI  - Avoidance of an aposematically coloured butterfly by wild birds in a tropical
      forest.
AB  - 1. Birds are considered to be the primary selective agents for warning
      colouration in butterflies, and select for aposematic mimicry by learning to
      avoid brightly coloured prey after unpleasant experiences. It has long been
      thought that bright colouration plays an important role in promoting the
      avoidance of distasteful prey by birds. 2. The hypothesis that warning
      colouration facilitates memorability and promotes predator avoidance was tested
      by means of a field experiment using distasteful model butterflies. Artificial
      butterflies with a Heliconius colour pattern unknown to local birds were
      generated using bird vision models, either coloured or achromatic, and hung in
      tree branches in a tropical forest. Two sequential trials were conducted at each
      site to test avoidance by naive and experienced predators. 3. There was a
      significant reduction in predation in the second trial. Also, coloured models
      were attacked less than achromatic models. Specifically, coloured butterflies
      were attacked significantly less in the second trial, but there was no
      significant decrease in predation on achromatic models. 4. The present results
      imply an important role for colour in enhancing aversion of aposematic
      butterflies. It has also been demonstrated that previous experience of
      distasteful prey can lead to enhanced avoidance in subsequent trials, supporting
      mimicry theory.

PMID- 27708482
TI  - Scientometric Dilemma: Is H-index Adequate for Scientific Validity of Academic's
      Work?
AB  - H-index is an index that attempts to measure the productivity and impact of
      published work of scientists. H-index has several advantages - it combines
      productivity with echo, is not sensitive to extreme values in terms of articles
      without citation or to articles with above-average number of citations and
      directly enables the identification of the most relevant articles with regard to
      the number of citations received. H-index has great potential in the academic
      community, but it still has not realistic indicator of the quality of work of one
      author. Authors described most used indices for scientific assessment.

PMID- 27708483
TI  - Glycated Hemoglobin (HbA1c): Clinical Applications of a Mathematical Concept.
AB  - BACKGROUND AND PURPOSE: Glycated hemoglobin (HbA1c) reflects the cumulative
      glucose exposure of erythrocytes over a preceding time frame proportional to
      erythrocyte survival. HbA1c is thus an areal function of the glucose-time curve,
      an educationally useful concept to aid teaching and clinical judgment. METHODS:
      An ordinary differential equation is formulated as a parsimonious model of HbA1c.
      The integrated form yields HbA1c as an area-under-the-curve (AUC) of a glucose
      time profile. The rate constant of the HbA1c model is then derived using the
      validated regression equation in the ADAG study that links mean blood glucose and
      HbA1c with a very high degree of goodness-of-fit. RESULTS: This model has
      didactic utility to enable patients, biomedical students and clinicians to
      appreciate how HbA1c may be conceptually inferred from discrete blood glucose
      values using continuous glucose monitoring system (CGMS) or self-monitored blood
      glucose (SMBG) glucometer readings as shown in the examples. It can be
      appreciated how hypoglycemia can occur with rapid HbA1c decline despite poor
      glycemic control. CONCLUSIONS: Being independent of laboratory assay pitfalls,
      computed 'virtual' HbA1c serves as an invaluable internal consistency cross-check
      against laboratory-measured HbA1c discordant with SMBG readings suggestive of
      inaccurate/fraudulent glucometer records or hematologic disorders including
      thalassemia and hemoglobinopathy. This model could be implemented within portable
      glucometers, CGMS devices and even smartphone apps for deriving tentative
      'virtual' HbA1c from serial glucose readings as an adjunct to measured HbA1c.
      Such predicted 'virtual' HbA1c readily accessible via glucometers may serve as
      feedback to modify behavior and empower diabetic patients to achieve better
      glycemic control.

PMID- 27708484
TI  - Calcitonin Receptor AluI (rs1801197) and Taq1 Calcitonin Genes Polymorphism in 45
      and Over 45-year-old Women and their Association with Bone Density.
AB  - PURPOSE: Calcitonin receptor gene has also a polymorphism which is associated
      with bone mass density. This study evaluates the association between calcitonin
      receptor AluI (rs1801197) and Taq1 calcitonin genes polymorphism with bone
      density rate. METHODS: In this descriptive-analytical study in 2013 in
      southwestern Iran, 200 blood samples, per the Cochran sample size formula, were
      taken from women aged 45 and older. DNA was extracted from the samples using the
      phenol- chloroform method and the genomic fragments in question were proliferated
      using the polymerase chain reaction (PCR) method. RESULTS: The genotypic
      distribution of polymorphism AluI for TT, TC, and CC genotypes in control group
      was 31.4%, 38.6%, and 30% and in patients 25.4%, 55.4%, and 19.2%, respectively.
      There was no significant difference in polymorphism AluI between patients and
      control group and no significant association was found between this gene and bone
      density rate (P > 0.05). All patients and the individuals in the control group
      exhibited tt genotype for TaqI calcitonin gene and no significant association was
      found between these participants and osteoporosis. CONCLUSION: There was no
      association between two polymorphisms and osteoporosis, and between polymorphism
      of these two genes and osteoporosis development rate in the participants.

PMID- 27708485
TI  - DWI/ADC in Differentiation of Benign from Malignant Focal Liver Lesion.
AB  - MATERIAL AND METHODS: The study was of prospective-retrospective character. It
      was carried out at the AKH in Vienna (Austria), where 100 patients with focal
      liver lesions were included in the study. All patients underwent the routine MR
      sequences on appliances 1,5 and 3T (Siemens, Germany): T1, T2, HASTE, VIBE, and a
      DWI with three b values (b 50, b 300 b 600 s / mm2) and ADC map with ROI (regions
      of interest). The numerical value of ADC map was calculated, where n = 100 liver
      lesions, by two independent radiologists. RESULTS: On the basis of matching the
      PH finding statistically we get DWI accuracy of 96.8% for the assessment of liver
      lesions. The average numerical value of ADC in benign hepatic lesions (FNH,
      Hemangiomas) in our study amounted to 1.88 (1.326 to 2.48) x103 mm2 /s, while the
      value of malignant liver lesions (HCC, CCC, CRCLM) were significantly lower and
      amounted to 1.15 (1.024 to 1.343) x10-3 mm2 /s (Figure 2). Differences between
      the mean ADC of benign and malignant lesions showed a statistically significant
      difference with p <0.0005. In our research, we get cut-off for the ADC value of
      1,341x10-3 mm2 /s, which proved to be the optimal parameter for differentiation
      between benign and malignant lesions. CONCLUSION: Measuring ADC values with DWI
      as an additional MRI tool can help in oncological practice by distinguishing
      normal liver parenchyma from focal lesions, and in differentiating benign from
      malignant liver lesions, particularly in cases where administration of contrast
      is not possible.

PMID- 27708486
TI  - Typing of Methicillin Resistant Staphylococcus Aureus Using DNA Fingerprints by
      Pulsed-field Gel Electrophoresis.
AB  - BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) is responsible for
      a wide spectrum of nosocomial and community associated infections worldwide. The
      aim of this study was to analyze MRSA strains from the general population in
      Canton Sarajevo, B&H. METHODS: Our investigation including either phenotypic and
      genotypic markers such as antimicrobial resistance, pulsed-field gel
      electrophoresis (PFGE), SCC typing, and Panton-Valentine leukocidin (PVL)
      detection. RESULTS: Antimicrobial susceptibility: all MRSA isolates were
      resistant to the beta-lactam antibiotics tested, and all isolates were
      susceptible trimethoprim sulphamethoxazole, rifampicin, fusidic acid, linezolid
      and vancomycin. Sixty-eight per cent of the MRSA isolates were resistant to
      erythromycin, 5% to clindamycin, 5% to gentamicin and 4% to ciprofloxacin. After
      the PFGE analysis, the isolates were grouped into five similarity groups: A-E.
      The largest number of isolates belonged to one of two groups: C: 60 (60%) and D:
      27 (27%). In both groups C and D, SCCmec type IV was predominant (60% and 88, 8%,
      respectively). A total of 24% of the isolates had positive expression of PVL
      genes, while 76% showed a statistically significantly greater negative expression
      of PVL genes. CONCLUSION: SCCmec type IV, together with the susceptibility
      profile and PFGE grouping, is considered to be typical of CA-MRSA.

PMID- 27708487
TI  - The Use of Continuous Electrocardiographic Holter Monitoring in Pediatric
      Cardiology.
AB  - OBJECTIVE: To show the place and role of continuous electrocardiographic twenty
      four-hour ECG monitoring in daily clinical practice of pediatric cardiologists.
      METHODS: According to protocol, 2753 patients underwent dynamic continuous ECG
      Holter monitoring (data collected from the "Register of ECG Holter monitoring" of
      Pediatric Clinic, UCC Sarajevo in period April 2003- April 2015). RESULTS: There
      were 50,5% boys and 49,5% girls, aged from birth to 19 years (1,63% - neonates
      and infants, 2,6% - toddlers, 9,95% - preschool children, 35,5% - gradeschoolers
      and 50,3% children in puberty and adolescence). In 68,1% of patients Holter was
      performed for the first time. Indications for conducting Holter were: arrhythmias
      in 42,2% cases, precordial pain in 23,5%, suspicion of pre-excitation and/or pre
      excitation in 10%, crisis of consciousness in 8%, uncorrected congenital/acquired
      heart defects in 4,2%, operated heart defects in 3,7%, hypertension in 3,1%
      cases, control of the pacemaker in 1,63% and other causes in 3,5% cases.
      Discharge diagnosis after ECG Holter monitoring were: insignificant arrhythmias
      in 47,1% cases, wandering pacemaker in 21,3%, pre-excitation in 16,2%, benign
      ventricular premature beats in 6,3%, atrioventricular block in 3%, sinus pause in
      2.2% cases and other arrhythmias in 3,5%. In mentioned period 57 cases of Wolf
      Parkinson White syndrome were registered, in 4,5% of patients antiarrhythmic
      therapy was administered. Radiofrequent ablation was performed in 23 cases.
      CONCLUSION: The development of pediatric cardiac surgery has initiated
      development of pediatric arrhythmology as imperative segment of pediatric
      cardiology. Continuous ECG Holter monitoring has become irreplaceable method in
      everyday diagnostics and therapy of arrhythmias in children.

PMID- 27708488
TI  - Efficacy of Multidetector-Row Computed Tomography as a Practical Tool in
      Comparison to Invasive Procedures for Visualization of the Biliary Obstruction.
AB  - INTRODUCTION: Recently, multidetector computed tomography (MDCT) has been
      introduced into clinical practice. MDCT has become the noninvasive diagnostic
      test of choice for detailed evaluation of biliary obstruction. AIM: the main
      objective of the present study was to evaluate the diagnostic value of MDCT
      compared to invasive procedures for detecting biliary obstruction causes.
      MATERIAL AND METHODS: Since February 2009 until May 2011 fifty biliary
      obstruction patients based on clinical, laboratory or ultrasonographic findings,
      were evaluated by Multidetector-row computed tomography. The causes of biliary
      obstruction, which was identified using. MDCT were classified into three
      categories: calculus, benign stricture, and malignancy. Final diagnosis was
      conducted based on percutaneous transhepatic cholangiography (PTC), endoscopic
      retrograde cholangiopancreatography, biopsy, or surgery. The MDCT diagnosis and
      were compared with the final diagnosis. RESULTS: A correct diagnosis of causes of
      biliaryobstruction was made on the basis of MDCT findings for 44 of the total 50
      patients. Two patients with chronic pancreatitis were incorrectly diagnosed with
      a pancreatic head adenocarcinoma on the basis of MDCT findings. One patient with
      biliary stone was incorrectly diagnosed with a periampullary adenocarcinoma on
      the basis of MDCT findings. The Sensitivity, specificity and accuracy of MDCT in
      the diagnosis of causes of biliary obstruction were 94.12% and87.87% and94.6%
      respectively. CONCLUSION: Based on the findings of this study MDCT has an
      excellent image quality, providing valuable information about the biliary tree
      and other abdominal organs. The use of advanced image processing, including
      maximum intensity projection and multiplanar reconstruction (especially coronal
      or sagittal reformatted images), allows superior visualization of the biliary
      tree and vascular structures. Three-dimensional reconstruction images complement
      axial images by providing a more anatomically meaningful display of the lesion
      and its relationship to adjacent structures, and accurate determining the
      craniocaudal extent of the lesion. High accuracy, wide availability and ease of
      use, make the MDCT the imaging modality of choice for evaluation of biliary
      obstruction.

PMID- 27708490
TI  - Designing and Implementation of Fuzzy Case-based Reasoning System on Android
      Platform Using Electronic Discharge Summary of Patients with Chronic Kidney
      Diseases.
AB  - INTRODUCTION: Case-based reasoning (CBR) systems are one of the effective methods
      to find the nearest solution to the current problems. These systems are used in
      various spheres as well as industry, business, and economy. The medical field is
      not an exception in this regard, and these systems are nowadays used in the
      various aspects of diagnosis and treatment. METHODOLOGY: In this study, the
      effective parameters were first extracted from the structured discharge summary
      prepared for patients with chronic kidney diseases based on data mining method.
      Then, through holding a meeting with experts in nephrology and using data mining
      methods, the weights of the parameters were extracted. Finally, fuzzy system has
      been employed in order to compare the similarities of current case and previous
      cases, and the system was implemented on the Android platform. DISCUSSION: The
      data on electronic discharge records of patients with chronic kidney diseases
      were entered into the system. The measure of similarity was assessed using the
      algorithm provided in the system, and then compared with other known methods in
      CBR systems. CONCLUSION: Developing Clinical fuzzy CBR system used in Knowledge
      management framework for registering specific therapeutic methods, Knowledge
      sharing environment for experts in a specific domain and Powerful tools at the
      point of care.

PMID- 27708489
TI  - Biomechanical Stability of Juvidur and Bone Models on Osteosyntesic Materials.
AB  - INTRODUCTION: Artificial models can be useful at approximate and qualitative
      research, which should give the preliminary results. Artificial models are
      usually made of photo-elastic plastic e.g.. juvidur, araldite in the three
      dimensional contour shape of the bone. Anatomical preparations consist of the
      same heterogeneous, structural materials with extremely anisotropic and unequal
      highly elastic characteristics, which are embedded in a complex organic
      structure. THE AIM OF THE STUDY: Examine the budget voltage and deformation of:
      dynamic compression plate (DCP), locking compression plate (LCP), Mitkovic
      internal fixator (MIF), Locked intramedullary nailing (LIN) on the compressive
      and bending forces on juvidur and veal bone models and compared the results of
      these two methods (juvidur, veal bone). MATERIAL AND METHODS: For the
      experimental study were used geometrically identical, anatomically shaped models
      of Juvidur and veal bones diameter of 30 mm and a length of 100 mm. Static tests
      were performed with SHIMADZU AGS-X testing machine, where the force of pressure
      (compression) increased from 0 N to 500 N, and then conducted relief. Bending
      forces grew from 0 N to 250 N, after which came into sharp relief. RESULTS: On
      models of juvidur and veal bones studies have confirmed that uniform stability at
      the site of the fracture MIF with a coefficient ranking KMIF=0,1971, KLIN=0,2704,
      KDCP=0,2727 i KLCP=0,5821. CONCLUSION: On models of juvidur and veal bones
      working with Shimadzu AGS-X testing machine is best demonstrated MIF with a
      coefficient of 0.1971.

PMID- 27708491
TI  - The Relation between Iranian Medical Science Research in PubMed and Burden of
      Disease.
AB  - INTRODUCTION: Scientific productions have been accelerated in Iran in past
      decades but its association with health problems and disease burden is doubtful.
      The aim of this study is assessment of the relationship between scientific
      productions with disease burden in Iran in PubMed dataset during 2010 to 2014.
      METHOD: The study was performed with the library method. Data Gathered using
      Scientometrics indicators and direct observation. The current research includes
      all articles written by Iranian researchers during 2010 to 2014 which were
      published in PubMed-indexed journals. The search was performed using keywords
      included road accident, ischaemic heart diseases, major depression disorders and
      cerebral vascular diseases. RESULTS: In total 910 articles had been published
      PubMed -indexed journals. Among them Substance-Related Disorders and Accidents,
      Traffic had the highest (263 records) and lowest (94 records) records
      respectively. There was not a direct correlation between Years of Life Lost,
      Years Lost due to Disability and mortality rate with scientific productions.
      CONCLUSIONS: our results showed Iranian scientific productions in PubMed data set
      are not related to disease burden however they are not related to high mortality
      diseases.

PMID- 27708492
TI  - Organism Encumbrance of Cardiac Surgeon During Surgery.
AB  - INTRODUCTION: Most everyday activities, performed over a long period leads to
      performance degradation of skeletal muscles as well as spinal column which is
      reflected in the reduction of maximum force, reduction of the speed of response,
      reducing control of the movement etc. Although until now many mathematical models
      of muscles are developed, very small number takes into account the fatigue, and
      those models that take into account changes in the characteristics of muscles for
      extended activities, generally considered tiring under certain conditions. Given
      that the current models of muscle fatigue under arbitrary conditions of
      activation and load are very limited, this article presents a new model that
      includes scale of muscles overload. MATERIAL AND METHODS: There are three female
      cardiac surgeons working performing these surgeries in operating rooms, and their
      average anthropometric measures for this population is: a) Weight: 62 kg; b)
      Height: 166 cm. Age: 45 taken in the calculation within the CATIA software, that
      entity is entitled to 50% of healthy female population that is able to execute
      these and similar jobs. During the surgery is investigated the two most common
      positions: position "1" and "2". We wish to emphasize that the experiment or
      surgical procedure lasted for two positions for five hours, with the position "1"
      lasted 0.5 hours, and position "2" lasted about 4.5 hours. The additional load
      arm during surgery is about 1.0 kg. RESULTS: The analysis was done in three
      positions: "Operating position 1", "Operating position 2 ', and each of these
      positions will be considered in its characteristic segments. These segments are:
      when the body takes the correct position, but is not yet burdened with external
      load, then when the surgeon receives the load and the third position when the
      load is lifted at the end of the position. Calculation of internal energy used on
      the joints is carried out in the context of software analysis of this model using
      CATIA R5v19. The proposed model is based on CATIA software model, which consists
      of visual indicators of the burden on certain parts of the body as well as the
      forces acting in these parts of the body. CONCLUSION: Based on these indicators
      to define which muscles, as well as that part of the skeletal system is
      overloaded, what is the position and what needs to be done that specific load be
      within permitted limits.

PMID- 27708493
TI  - Quantitative Assessment of Theses at Mazandaran University of Medical Sciences
      Years-(1995-2014).
AB  - BACKGROUND: Review and evaluation of research for the correct steps towards real
      progress is essential which is a healthy and dynamic feature of the system. For
      the correct step toward real progress, evaluation research is essential which is
      feature of healthy and dynamic system. Considering the importance of scientific
      thesis in production and development and be aware of as the lack of structured
      information and qualitative and quantitative assessment at Mazandaran University
      of Medical Sciences, therefore we decided to do qualitative stud of theirs
      prepared 1995-2014. METHODS: This study was a descriptive survey, a sample of 325
      graduate and PhD thesis and dissertation in clinical and basic science at the
      university of medical sciences of the population in 2060 is a thesis from 1994 to
      the end of 2014. To study the population, stratified sampling method was used.
      The descriptive study was conducted in terms of matching the degree thesis
      students, theses subjects, specialty of supervisors and Advisers. The data
      gathering tool was checklist of information (gender, discipline, degree and
      department education of students, School, year of dependence, title of theses and
      dissertations, specialty and departments of supervisors and advisers, type of
      research, grade obtained of students). Statistical analysis of the data was
      performed using 21 SPSS software. RESULTS: We studied 325 theses; 303
      dissertations which 1 researcher; 21 dissertations which 2 researchers and 1
      dissertation with 3 researchers. A total of 348 students (174 females and 174
      males) researcher had theses. The number of students in the Department of Basic
      Science 82 (23.5%), 266 (76.5 %) in clinical group; 29(8.33%), 29 (8.33%) master
      degree; 260 (74.71%) general practitioner; 58 (16.67%) specialty and 1(29) at the
      PhD level. There was no relationship between research and level of education (p =
      0.081). However, it was found that majority of the theses for the general
      practitioner (59.8%) wryer type 1(status condition). By matching and determining
      the overlapping of specialty of the advisor and the guide with the title, titles
      of the theses. It was found that 298 (91.69%) of the theses correspond with the
      specialty of the advisors and the supervisors. CONCLUSION: Based on the results
      obtained on the review of the theses to direct students to fundamental research
      and applying of specialized groups of supervisors and advisers in accordance with
      research is felt. No doubt that in the future will improve the quality of the
      students' theses.

PMID- 27708495
TI  - Needs Assessment of Pathologists Using Telepathology Systems.
AB  - BACKGROUND: This project sought to identify the most common telepathology
      consultation needs of pathologists based on the anatomic section of tissue to
      improve quality of consultations. METHODS: This cross-sectional study used a
      questionnaire with four questions to assess pathologists' consultation needs. The
      questionnaire was distributed to the 16 pathologists recruited for this study.
      All 16 of the pathologists work in Kerman province, the largest province of Iran,
      which is situated 1,000 kilometers from Tehran, Iran's capital city. RESULTS: On
      average, the pathologists expressed a need to consult with their colleagues in
      7.5% of cases. They believed that articular and bone tissue, soft tissue and the
      lymphoid system (respectively in descending order) to be the three anatomical
      parts that require the greatest amount of consultation. As such, consultant
      pathologists should ensure they have particular expertise in articular and bone
      tissue, soft tissue and the lymphoid system. CONCLUSION: This study demonstrated
      that pathologists most need advice from consultants when working with samples of
      articular and bone tissue, soft tissue and the lymphoid system. These results can
      be used to ensure successful implementation of telepathology systems, which are
      helpful for consultation from rural and remote areas.

PMID- 27708497
TI  - The Most Influential Scientists in the Development of Medical informatics (13):
      Margaret Belle Dayhoff.

PMID- 27708496
TI  - Value of Positron Emission Tomography/Computed Tomography (PET-CT) in Suspected
      Non-small Cell Lung Cancer Recurrence and Impact on Patient Management.
AB  - INTRODUCTION: Positron emission tomography/computed tomography (PET-CT) is very
      sensitive for diagnosis of recurrent NSCLC and has a significant impact on change
      of management. Preliminary data suggest superiority of PET-CT comparing to CT
      alone for lung cancer restaging. MATERIALS AND METHODS: This is a retrospective
      study which aim is to validate usage of PET-CT in suspected non-small cell lung
      carcinoma recurrence and its impact on further patient management. Total number
      of 31 patients with non-small cell lung carcinoma and uncertain diagnosis of
      recurrent disease or its extent after routine clinical and CT work-up were
      enrolled in this study. DISCUSSION: We found in our study that PET-CT diagnosed
      recurrent disease in 65% of patients who were previously presented with an
      indeterminante CT. In 85% of patients there were change in further management.
      CONCLUSION: We suggest that PET should be performed on patients who have
      suspected relapse after potentially curative treatment, particularly if active
      treatment is being considered. PET-CT improved the diagnosis of recurrent NSCLC
      and this resulted in a significant impact and change in further patient
      management.

PMID- 27708498
TI  - 14th International Conference on Informatics, Management and Technology in
      Healthcare, Athens, Greece, 1-3 July, 2016.

PMID- 27708494
TI  - Teleconsultation and Clinical Decision Making: a Systematic Review.
AB  - BACKGROUND: The goal of teleconsultation is to omit geographical and functional
      distance between two or more geographically separated health care providers. The
      purpose of present study is to review and analyze physician-physician
      teleconsultations. METHOD: The PubMed electronic database was searched. The
      primary search was done on January 2015 and was updated on December 2015. A fetch
      and tag plan was designed by the researchers using an online Zotero library.
      RESULTS: 174 full-text articles of 1702 records met inclusion criteria.
      Teleconsultation for pediatric patients accounts for 14.36 percent of accepted
      articles. Surgery and general medicine were the most prevalent medical fields in
      the adults and pediatrics, respectively. Most teleconsultations were inland
      experiences (no=135), and the USA, Italy and Australia were the three top
      countries in this group. Non-specialists health care providers/centers were the
      dominant group who requested teleconsultation (no=130). Real time, store and
      forward, and hybrid technologies were used in 50, 31, and 16.7 percent of
      articles, respectively. The teleconsultation were reported to result in change in
      treatment plan, referral or evacuation rate, change in diagnosis, educational
      effects, and rapid decision making. Use of structured or semi-structured template
      had been noticed only in a very few articles. CONCLUSION: The present study
      focused on the recent ten years of published articles on physician-physician
      teleconsultations. Our findings showed that although there are positive impacts
      of teleconsultation as improving patient management, still have gaps that need to
      be repaired.

PMID- 27708499
TI  - Hyperspectral volumetric coherent anti-Stokes Raman scattering microscopy:
      quantitative volume determination and NaCl as non-resonant standard.
AB  - In this work, we demonstrate quantitative volume determination of chemical
      components in three dimensions using hyperspectral coherent anti-Stokes Raman
      scattering microscopy, phase-corrected Kramers-Kronig retrieval of the coherent
      anti-Stokes Raman scattering susceptibility and factorization into concentration
      of chemical components. We investigate the influence of the refractive index
      contrast between water and polymer beads (polystyrene and
      polymethylmethacrylate), showing that it leads mainly to concentration errors,
      while the spectral error is less affected. The volume of polystyrene beads of
      sizes from 200 nm to 3 MUm is determined with 10% relative error and 1% absolute
      error in the region of interest. We furthermore establish the use of sodium
      chloride as non-resonant reference material free of Raman-active vibrational
      resonances.

PMID- 27708500
TI  - Rate Constants and Activation Energies for Gas-Phase Reactions of Three Cyclic
      Volatile Methyl Siloxanes with the Hydroxyl Radical.
AB  - Reaction with hydroxyl radicals (OH) is the major pathway for removal of cyclic
      volatile methyl siloxanes (cVMS) from air. We present new measurements of second
      order rate constants for reactions of the cVMS octamethylcyclotetrasiloxane (D4),
      decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) with OH
      determined at temperatures between 313 and 353 K. Our measurements were made
      using the method of relative rates with cyclohexane as a reference substance and
      were conducted in a 140-mL gas-phase reaction chamber with online mass
      spectrometry analysis. When extrapolated to 298 K, our measured reaction rate
      constants of D4 and D5 with the OH radical are 1.9 * 10-12 (95% confidence
      interval (CI): (1.7-2.2) * 10-12) and 2.6 * 10-12 (CI: (2.3-2.9) * 10-12) cm3
      molecule-1 s-1, respectively, which are 1.9* and 1.7* faster than previous
      measurements. Our measured rate constant for D6 is 2.8 * 10-12 (CI: (2.5-3.2) *
      10-12) cm3 molecule-1 s-1 and to our knowledge there are no comparable laboratory
      measurements in the literature. Reaction rates for D5 were 33% higher than for D4
      (CI: 30-37%), whereas the rates for D6 were only 8% higher than for D5 (CI: 5
      10%). The activation energies of the reactions of D4, D5, and D6 with OH were not
      statistically different and had a value of 4300 +/- 2800 J/mol.

PMID- 27708501
TI  - The Social Costs of Gender Nonconformity for Transgender Adults: Implications for
      Discrimination and Health.
AB  - Research suggests that transgender people face high levels of discrimination in
      society, which may contribute to their disproportionate risk for poor health.
      However, little is known about whether gender nonconformity, as a visible marker
      of one's stigmatized status as a transgender individual, heightens trans people's
      experiences with discrimination and, in turn, their health. Using data from the
      largest survey of transgender adults in the United States, the National
      Transgender Discrimination Survey (N = 4,115), we examine the associations among
      gender nonconformity, transphobic discrimination, and health-harming behaviors
      (i.e., attempted suicide, drug/alcohol abuse, and smoking). The results suggest
      that gender nonconforming trans people face more discrimination and, in turn, are
      more likely to engage in health-harming behaviors than trans people who are
      gender conforming. Our findings highlight the important role of gender
      nonconformity in the social experiences and well-being of transgender people.

PMID- 27708502
TI  - Methodological considerations in the use of audio diaries in work psychology:
      Adding to the qualitative toolkit.
AB  - : The use of longitudinal methodology as a means of capturing the intricacies in
      complex organizational phenomena is well documented, and many different research
      strategies for longitudinal designs have been put forward from both a qualitative
      and quantitative stance. This study explores a specific emergent qualitative
      methodology, audio diaries, and assesses their utility for work psychology
      research drawing on the findings from a four-stage study addressing transient
      working patterns and stress in UK temporary workers. Specifically, we explore
      some important methodological, analytical and technical issues for practitioners
      and researchers who seek to use these methods and explain how this type of
      methodology has much to offer when studying stress and affective experiences at
      work. We provide support for the need to implement pluralistic and complementary
      methodological approaches in unearthing the depth in sense-making and assert
      their capacity to further illuminate the process orientation of stress.
      PRACTITIONER POINTS: This study illustrates the importance of verbalization in
      documenting stress and affective experience as a mechanism for accessing
      cognitive processes in making sense of such experience.This study compares audio
      diaries with more traditional qualitative methods to assess applicability to
      different research contexts.This study provides practical guidance and a
      methodological framework for the design of audio diary research and design,
      taking into account challenges and solutions for researchers and practitioners.

PMID- 27708504
TI  - Carboniferous Onychophora from Montceau-les-Mines, France, and onychophoran
      terrestrialization.
AB  - The geological age of the onychophoran crown-group, and when the group came onto
      land, have been sources of debate. Although stem-group Onychophora have been
      identified from as early as the Cambrian, the sparse record of terrestrial taxa
      from before the Cretaceous is subject to contradictory interpretations. A Late
      Carboniferous species from the Mazon Creek biota of the USA, Helenodora
      inopinata, originally interpreted as a crown-group onychophoran, has recently
      been allied to early Cambrian stem-group taxa. Here we describe a fossil species
      from the Late Carboniferous Montceau-les-Mines Lagerstatte, France, informally
      referred to as an onychophoran for more than 30 years. The onychophoran
      affinities of Antennipatus montceauensis gen. nov., sp. nov. are indicated by the
      form of the trunk plicae and the shape and spacing of their papillae, details of
      antennal annuli, and the presence of putative slime papillae. The poor
      preservation of several key systematic characters for extant Onychophora,
      however, prohibits the precise placement of the Carboniferous fossil in the stem
      or crown of the two extant families, or the onychophoran stem-group as a whole.
      Nevertheless, A. montceauensis is the most compelling candidate to date for a
      terrestrial Paleozoic onychophoran.

PMID- 27708503
TI  - Tuning supramolecular G-quadruplexes with mono- and divalent cations.
AB  - Supramolecular G-quadruplexes (SGQs) are formed via the cation promoted self
      assembly of guanine derivatives into stacks of planar hydrogen-bonded tetramers.
      Here, we present results on the formation of SGQs made from the 8-(m
      acetylphenyl)-2'-deoxyguanosine (mAGi) derivative in the presence of various mono
      and divalent cations. NMR and HR ESI-MS data indicate that varying the cation
      can efficiently tune the molecularity, the fidelity and stability (thermal and
      kinetic) of the resulting SGQs. The results show that, parallel to the previously
      reported potassium-templated hexadecamer (mAGi16.3K+), Na+, Rb+ and [Formula: see
      text] also promote the formation of similar supramolecules with high fidelity and
      molecularity. In contrast, the divalent cations Pb2+, Sr2+ and Ba2+ template the
      formation of octamers (mAGi8), with the latter two inducing higher thermal
      stabilities. Molecular dynamics simulations for the hexadecamers containing
      monovalent cations enabled critical insights that help explain the experimental
      observations.

PMID- 27708506
TI  - Barrett's esophagus: lessons from recent clinical trials.
AB  - Data from recent studies cast doubt on former recommendations on diagnosis and
      management of Barrett's esophagus. Based on latest research findings several
      Gastroenterological Associations actualized their guidelines and international
      experts compiled consensus statements as practical help for clinicians. In this
      review we discuss recent trials and their impact on clinical practice, current
      recommendations and persisting controversies in Barrett's esophagus.

PMID- 27708508
TI  - Fast-track drug approval in inflammatory bowel diseases.
AB  - Fast-track drug designation of safe regimens represents an emerging method of
      development and approval of new medications targeting debilitating diseases
      including inflammatory bowel diseases (IBD). The goal of accelerated drug
      approval pathways is to shorten the time between application and approval of
      therapies that treat diseases with significant morbidity and mortality. Recently,
      fast-track drug approval approaches were supported by data deriving from central
      reading of images, a method of clinical data interpretation that has
      significantly benefited patients with gastrointestinal disorders. Biological
      agents and other emerging therapies in IBD represent "game-changing" or "treat-to
      target" drugs and have satisfied quite successfully some of the patients' unmet
      needs. The development of biosimilars is an area where the Federal Drug
      Administration and the European Agency for Evaluation of Medicinal Products seem
      to have different approval processes. Biosimilars, including those for IBD,
      promise cost reductions and wide access to biologic therapies by patients,
      advantages similar to those already offered by generic drugs. Given the rapid
      development of IBD drugs and patients' needs, a consensus among the academic
      community, clinicians, researchers, sponsors, patients and regulatory authorities
      is required to standardize better the IBD trials and create a productive
      environment for fast-track approval of any "changing-game" IBD drug.

PMID- 27708507
TI  - Adipokines and the role of visceral adipose tissue in inflammatory bowel disease.
AB  - Recently, adipocytes have been recognized as actively participating in local and
      systemic immune responses via the secretion of peptides detectable in relevant
      levels in the systemic circulation, the so-called "adipo(cyto)kines". Multiple
      studies appearing within the last 10-15 years have focused on the possible impact
      of adipose tissue depots on inflammatory bowel disease (IBD). Consequently,
      various hypotheses regarding the role of different adipokines in inflammatory
      diseases in general and in intestinal inflammatory processes in particular have
      been developed and have been further refined in recent years. After a focused
      summary of the data reported concerning the impact of visceral adipose tissue on
      IBD, such as Crohn's disease and ulcerative colitis, our review focuses on recent
      developments indicating that adipocytes as part of the innate immune system
      actively participate in antimicrobial host defenses in the context of intestinal
      bacterial translocation, which are of utmost importance for the homeostasis of
      the whole organism. Modulators of adipose tissue function and regulators of
      adipokine secretion, as well as modifiers of adipocytic pattern recognition
      molecules, might represent future potential drug targets in IBD.

PMID- 27708505
TI  - Clinical practice guidelines for the management of metastatic colorectal cancer:
      a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO).
AB  - There is discrepancy and failure to adhere to current international guidelines
      for the management of metastatic colorectal cancer (CRC) in hospitals in Greece
      and Cyprus. The aim of the present document is to provide a consensus on the
      multidisciplinary management of metastastic CRC, considering both special
      characteristics of our Healthcare System and international guidelines. Following
      discussion and online communication among the members of an executive team chosen
      by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic
      CRC disease was developed. Statements were subjected to the Delphi methodology on
      two voting rounds by invited multidisciplinary international experts on CRC.
      Statements reaching level of agreement by >=80% were considered as having
      achieved large consensus, whereas statements reaching 60-80% moderate consensus.
      One hundred and nine statements were developed. Ninety experts voted for those
      statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In
      the end of the process, all statements achieved a large consensus. The importance
      of centralization, care by a multidisciplinary team, adherence to guidelines, and
      personalization is emphasized. R0 resection is the only intervention that may
      offer substantial improvement in the oncological outcomes.

PMID- 27708509
TI  - Evaluation of liver fibrosis: "Something old, something new...".
AB  - Hepatic fibrogenesis may gradually result to cirrhosis due to the accumulation of
      extracellular matrix components as a response to liver injury. Thus, therapeutic
      decisions in chronic liver disease, regardless of the cause, should first and
      foremost be guided by an accurate quantification of hepatic fibrosis. Detection
      and assessment of the extent of hepatic fibrosis represent a challenge in modern
      Hepatology. Although traditional histological staging systems remain the "best
      standard", they are not able to quantify liver fibrosis as a dynamic process and
      may not accurately substage cirrhosis. This review aims to compare the currently
      used non-invasive methods of measuring liver fibrosis and provide an update in
      current tissue-based digital techniques developed for this purpose, that may
      prove of value in daily clinical practice.

PMID- 27708510
TI  - Fibrosing cholestatic hepatitis C in post-transplant adult recipients of liver
      transplantation.
AB  - Hepatitis C recurrence continues to present a major challenge in liver
      transplantation (LT). Approximately 10% of hepatitis C virus (HCV)-positive
      recipients will develop fibrosing cholestatic hepatitis (FCH) after LT. FCH is
      clinically characterized as marked jaundice with cholestatic hepatic dysfunction
      and high titers of viremia. Pathologically, FCH manifests as marked hepatocyte
      swelling, cholestasis, periportal peritrabecular fibrosis and only mild
      inflammation. This progressive form usually involves acute liver failure, and
      rapidly results in graft loss. A real-time and precise diagnosis based on
      histopathological examination and viral measurement is indispensable for the
      adequate treatment of FCH. Typical pathological findings of FCH are shown.
      Currently, carefully selected combinations of direct-acting antivirals (DAAs)
      offer the potential for highly effective and safe regimens for hepatitis C, both
      in the pre- and post-transplant settings. Here, we review FCH caused by HCV in LT
      recipients, and current strategies for sustained virological responses after LT.
      Only a few cases of successfully treated FCH C after LT by DAAs have been
      reported. The diagnostic findings and therapeutic dilemma are discussed based on
      a literature review.

PMID- 27708511
TI  - Current role of microwave ablation in the treatment of small hepatocellular
      carcinomas.
AB  - Percutaneous radiofrequency ablation (RFA) can be as effective as surgical
      resection in terms of overall survival and recurrence-free survival rates in
      patients with small hepatocellular carcinoma (HCC). Effectiveness of RFA is
      adversely influenced by heat-sink effect. Other ablative therapies could be
      considered for larger tumors or for tumors located near the vessels. In this
      regard, recent improvements in microwave energy delivery systems seem to open
      interesting perspectives to percutaneous ablation, which could become the
      ablation technique of choice in the near future. Microwave ablation (MWA) has the
      advantages of possessing a higher thermal efficiency. It has high efficacy in
      coagulating blood vessels and is a relatively fast procedure. The time required
      for ablation is short and the shape of necrosis is elliptical with the older
      systems and spherical with the new one. There is no heat-sink effect and it can
      be used to ablate tumors adjacent to major vessels. These factors yield a large
      ablation volume, and result in good local control and fewer complications. This
      review highlights the most relevant updates on MWA in the treatment of small (<3
      cm) HCC. Furthermore, we discuss the possibility of MWA as the first ablative
      choice, at least in selected cases.

PMID- 27708513
TI  - Percutaneous endoscopic colostomy: a useful technique when surgery is not an
      option.
AB  - Percutaneous endoscopic colostomy (PEC) is a minimally invasive endoscopic
      procedure that offers an alternative treatment for high-risk patients with
      sigmoid volvulus or intestinal pseudo-obstruction who have tried conventional
      treatment options without success or those who are unfit for surgery. The
      procedure acts as an irrigation or decompressing channel and provides colonic
      'fixation' to the anterior abdominal wall. The risk of complications highlights
      the importance of informed consent for patients and relatives.

PMID- 27708512
TI  - Genetic factors affecting patient responses to pancreatic cancer treatment.
AB  - Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical
      resection is the only possible curative mode of treatment. Metastatic pancreatic
      cancer is incurable with modest results from the current treatment options. New
      genomic information could prove treatment efficacy. An independent review of
      PubMed and ScienceDirect databases was performed up to March 2016, using
      combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic
      profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic
      pathogenesis, and targeted therapy. Recent genetic studies have identified new
      markers and therapeutic targets. Our current knowledge of pancreatic cancer
      genetics must be further advanced to elucidate the molecular basis and
      pathogenesis of the disease, improve the accuracy of diagnosis, and guide tailor
      made therapies.

PMID- 27708514
TI  - Airway observations during upper endoscopy predicting obstructive sleep apnea.
AB  - BACKGROUND: This pilot study examined airway characteristics during upper
      endoscopy to determine who is at high risk for obstructive sleep apnea. METHODS:
      Patients undergoing routine upper endoscopy were divided into 2 groups according
      to the Berlin Questionnaire (high and low risk for sleep disordered breathing).
      Patients underwent routine upper endoscopy using propofol sedation. The airway
      was then evaluated for no, partial, or complete collapse at the levels of the
      palate/uvula/tonsils, the tongue base, the hypopharynx, and the larynx. They were
      given a score of 0 for no collapse, 1 for partial collapse, and 2 for complete
      collapse. The score for each of these levels was added to give a total score or
      severity index. The larynx was also evaluated for lateral pharyngeal collapse
      (minimal, up to 50%, >50%, or 100%). RESULTS: We found that patients with a
      partial obstruction at the level of the palate/uvula/tonsils, tongue base,
      hypopharynx, or larynx, or complete obstruction at any level more often had a
      positive Berlin questionnaire. Patients with a positive Berlin questionnaire were
      more often of increased weight (mean 197 vs 175 lbs, P=0.19), increased body mass
      index (31.2 vs 27.42 kg/m2, P=0.11), increased neck circumference (36.7 vs 34.7
      cm, P=0.23), and had a higher total airway score (2.61 vs 1.67, P=0.09).
      CONCLUSIONS: The results of our pilot study represent preliminary data regarding
      the use of upper endoscopy as a potential tool to evaluate patients for
      obstructive sleep apnea.

PMID- 27708515
TI  - Irritable bowel syndrome might be associated with dry eye disease.
AB  - BACKGROUND: A possible association between dry eye disease (DED) and irritable
      bowel syndrome (IBS) has been hypothesized based on the fact that they both share
      an inflammatory pathogenesis. METHODS: Ninety-five patients with IBS and 276
      healthy controls were enrolled in the study. All patients answered a
      questionnaire regarding DED symptoms and had a complete ophthalmic examination.
      DED signs were evaluated using Schirmer's 1 and tear break-up time (tBUT) tests
      in both groups. RESULTS: Female IBS participants presented significantly lower
      Schirmer's test and tBUT (P=0.002 and P<0.001 respectively) than controls. Both
      diagnostic tests in male IBS patients were also significantly lower than in
      controls (P<0.001). 72% of IBS patients gave at least 3 positive answers to the
      questionnaire compared with 42% of the control group (P<0.01). CONCLUSION: Our
      results suggest a correlation between IBS and DED. DED symptoms can cause further
      complications in patients with IBS, and should be considered in their management.
      However, further research is needed to establish a possible pathophysiologic
      association.

PMID- 27708516
TI  - Inflammatory bowel disease nurse specialists for patients on biological
      therapies: a nationwide Italian survey.
AB  - BACKGROUND: Management of inflammatory bowel disease (IBD) patients requires a
      multidisciplinary approach. Among the working team, the role of IBD nurse is
      expected to be particularly relevant when managing patients receiving biological
      therapies. We performed a survey to assess the presence of IBD nurse in centers
      where patients were receiving biologics. METHODS: For this Italian nationwide
      survey a specific questionnaire was prepared. IBD nurse was defined as a nurse
      directly involved in all phases of biological therapy, from pre-therapy
      screening, administration and monitoring during therapy, to follow up performed
      by a dedicated helpline, completed a specific training on biological therapy
      therapy, and observed international guidelines. RESULTS: A total of 53 Italian
      IBD centers participated in the survey, and 91 valid questionnaires were
      collected. Overall, 34 (37.4%) nurses could be classified as IBD specialists. IBD
      nurses had a significantly higher educational level than other nurses, they were
      more frequently operating in Central or Southern than in Northern Italy, they
      were working in an Academic center rather than in a General hospital, and in IBD
      centers with >25 patients on biological therapy. On the contrary, mean age,
      gender distribution, years of nursing, and years working in the IBD unit did not
      significantly differ between IBD and other nurses. CONCLUSIONS: Our nationwide
      survey showed that the presence of an IBD nurse is still lacking in the majority
      of Italian IBD centers where patients receive biological therapies, suggesting a
      prompt implementation.

PMID- 27708517
TI  - Differences between morning and afternoon colonoscopies for adenoma detection in
      female and male patients.
AB  - BACKGROUND: Colonoscopies performed in the afternoon (PM) have been shown to have
      lower adenoma detection rates (ADR) compared to those in the morning (AM).
      Endoscopist fatigue has been suggested as a possible reason. Colonoscopies tend
      to be technically more challenging in female patients. Furthermore, women have a
      lower incidence of adenomas then men. The impact of the timing of colonoscopy
      based on sex has not been studied. We hypothesized that any decrease in ADR in PM
      colonoscopies would be more pronounced in female patients when compared to male
      patients. METHODS: We retrospectively reviewed colonoscopies performed for
      screening or surveillance in our outpatient endoscopy center from January 2008 to
      December 2011. Complete colonoscopies with a documented cecal intubation were
      included. All patients with a history of colorectal cancer or colonic resection,
      inadequate bowel preparation, or incomplete data were excluded. RESULTS: A total
      of 2305 patients (1207 female) were included. Overall, ADR was significantly
      higher in AM than in PM procedures. Multivariate analysis demonstrated that ADR
      for females was lower in PM than in AM colonoscopies (odds ratio [OR] 0.63, 95%
      confidence interval [CI] 0.44-0.91, P=0.015). There was a non-significant trend
      towards a lower ADR for males in PM (OR 0.84, 95% CI 0.62-1.15, P=0.28). Females
      had a prolonged intubation time and a longer procedure time. CONCLUSION: The
      difference in ADR between AM and PM procedures seems to apply mainly to female
      patients. No significant change in ADR was noted in male patients in the
      afternoon.

PMID- 27708518
TI  - Prophylactic clipping and post-polypectomy bleeding: a meta-analysis and
      systematic review.
AB  - BACKGROUND: Bleeding after polypectomy is a common issue associated with
      colonoscopy. To help prevent post-polypectomy bleeding, many endoscopists place
      clips at the site. However, this practice remains controversial. Therefore, we
      performed a meta-analysis of the efficacy of clip placement in the prevention of
      post-polypectomy bleeding. METHODS: Multiple databases, including Embase, Scopus,
      MEDLINE/PubMed, CINAHL, Cochrane databases, and recent abstracts from major
      American meetings were searched in April 2016. Using the DerSimonian and Laird
      (random effects) model with odds ratio (OR), a meta-analysis was performed of
      post-polypectomy bleeding with prophylactic clip versus no prophylactic clip.
      RESULTS: Five hundred and thirty potential articles and abstracts were
      discovered. Thirty-five articles were reviewed, with 12 studies satisfying the
      inclusion criteria. No statistically significant difference in prophylactic
      clipping versus no prophylactic clipping for post-polypectomy bleeding in all
      polyps was found when all studies (OR 1.49; 95% CI: 0.56-4.00; P=0.42), only peer
      reviewed studies where abstracts were excluded (OR 0.84; 95% CI: 0.42-1.69;
      P=0.63), and only randomized controlled trials (OR 1.24; 95% CI: 0.69-2.24;
      P=0.47) were analyzed. CONCLUSIONS: The use of prophylactic clipping for all
      polypectomies does not seem to prevent post-polypectomy bleeding and should not
      be a routine practice. However, for large polyps (>2 cm), prophylactic clipping
      may or may not be beneficial in preventing post-polypectomy bleeding. Further
      studies are required to fully evaluate this subgroup.

PMID- 27708519
TI  - Handgrip dynamometry: a surrogate marker of malnutrition to predict the prognosis
      in alcoholic liver disease.
AB  - BACKGROUND: The aim of the study was to determine the utility of handgrip
      dynamometry (HGD) in predicting short term mortality and complications in
      alcoholic liver disease. METHODS: Patients with alcoholic liver disease were
      included and nutritional assessment was done using the Subjective Global
      Assessment (SGA), HGD and other conventional parameters. Mortality rates and
      complications were compared to nutritional status. RESULTS: 80 patients were
      included in the study. Mean age of patients was 43.06+/-10.03 years. 69 patients
      survived and 11 patients died within the 3 month study duration. Handgrip
      strength (HGS) was higher in SGA A (28.76+/-5.48 kg) than SGA B (22.43+/-4.95 kg)
      and SGA C (16.78+/-3.83 kg) (P=<0.001). Number of complications including
      spontaneous bacterial Peritonitis, gastrointestinal bleeding and encephalopathy
      in SGA C group were 66.66%, in SGA B 20.75% and SGA A 10%. Mean HGS was
      significantly higher in the survivors (24.23+/-5.86) compared to non-survivors
      (18.04+/-4.82) (P=0.0011). There was a strong negative correlation between the
      HGS and Child-Pugh score (P=<0.0012). Multivariate logistic regression analysis
      to assess the risk factors for death showed handgrip to be in the suggestive
      significance range (P=0.072). The sensitivity of HGS was 88.41% in predicting
      short term mortality. CONCLUSIONS: HGS correlates with Child-Pugh score in
      predicting short term mortality. HGD is a simple, inexpensive and sensitive tool
      for assessing the nutritional status in alcoholic liver disease and can reliably
      predict its complications and survival.

PMID- 27708520
TI  - Predictors of hospital re-admissions among Hispanics with hepatitis C-related
      cirrhosis.
AB  - BACKGROUND: Hospital re-admissions in decompensated cirrhosis are associated with
      worse patient outcomes. Hispanics have a disproportionately high prevalence of
      hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study
      was to evaluate the factors affecting re-admission rates among Hispanics with HCV
      related cirrhosis. METHODS: A total of 292 consecutive HCV-related cirrhosis
      admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012
      were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The
      statistical analysis was performed using STATA version 11.1. Chi-square/Fisher's
      exact and Student's t-tests were used to compare categorical and continuous
      variables, respectively. Multivariate logistic regression analysis was performed
      to identify predictors for hospital readmissions. RESULTS: Among the 132
      cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics
      (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were
      the most frequent causes of the first and subsequent readmissions. Hispanics with
      readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher
      model for end-stage liver disease (MELD) scores (>=15), as well as a higher
      incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular
      carcinoma, and varices (P<0.05). The majority of the study patients (81%) had
      MELD scores <15. Multivariate regression analysis identified alcohol use (OR
      2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2),
      and CTP class (OR 3.3; 95%CI 1.4-8.1) as predictors for readmissions among
      Hispanics. CONCLUSION: CTP classes B and C, among other factors, were the major
      predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The
      majority of these readmissions were due to HE and variceal hemorrhage.

PMID- 27708521
TI  - Laparoscopic versus open liver resection for hepatocellular carcinoma: initial
      experience in Greece.
AB  - BACKGROUND: Liver resection represents the treatment of choice for a small
      proportion of patients with hepatocellular carcinoma (HCC), amenable to surgery.
      The remarkable evolution in surgical techniques during the last decades
      introduced laparoscopic hepatectomy in the operative management of HCC, even in
      the presence of liver cirrhosis. No comparative study on laparoscopic or open
      liver resection for HCC has been conducted in Greece yet. METHODS: Patients
      undergoing liver resection for HCC by one senior hepatobiliary surgeon in our
      Institution during the period 11/2011-02/2016 were prospectively sampled and
      retrospectively analyzed for the purposes of this study. Statistical analysis
      encompassed Student's t-test, Fisher's exact test, the Kaplan-Meier method/log
      rank test and Cox proportional hazard regression analyses. RESULTS: Eleven
      patients underwent laparoscopic and 21 open liver resection, respectively.
      Statistical differences between the 2 groups were observed for tumor size
      (P=0.04), major resections (P=0.01), Pringle maneuver (P=0.008), intraoperative
      blood transfusion (P=0.03), and duration of operation (P=0.004). Resection
      margins, and tumor recurrence showed no statistical differences. Three-year
      postoperative survival after laparoscopic and open hepatectomy was 100%, and 67%,
      respectively (P=0.06). Regression analysis for patient survival revealed
      prognostic value for BCLC staging, gamma-glutamyl transferase levels,
      laparoscopic hepatectomy, UICC stage, Dindo-Clavien classification, and hospital
      stay. Laparoscopic hepatectomy remained as independent predictor of survival by
      multivariate analysis (P=0.0142). CONCLUSION: Laparoscopic hepatectomy for HCC in
      chronic liver disease represents a safe and innovative treatment tool in the
      management of these patients under the presupposition of careful patient
      selection.

PMID- 27708524
TI  - Esophagogastric fistula: a rare complication of laparoscopic Nissen
      fundoplication.

PMID- 27708522
TI  - Anesthesia for endoscopic retrograde cholangiopancreatography: target-controlled
      infusion versus standard volatile anesthesia.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a technique
      used both for diagnosis and for the treatment of biliary and pancreatic diseases.
      ERCP has some anesthetic implications and specific complications. The primary
      outcome aim was to compare two protocols in terms of time of extubation. We also
      compared anesthetic protocols in terms of hemodynamic and respiratory
      instability, antispasmodics needs, endoscopist satisfaction, and recovery room
      stay. METHODS: Patients were randomized into two groups standard anesthesia group
      (Gr: SA) in whom induction was done by propofol, fentanyl and cisatracurium and
      maintenance was done by a mixture of oxygen, nitrousoxide (50%:50%) and
      sevoflurane; and intravenous anesthesia group to target concentration (Gr: TCI)
      in whom induction and maintenance of anesthesia were done with propofol with a
      target 0.5-2 MUg/mL, and remifentanil with a target of 0.75-2 ng/mL. RESULTS: 90
      patients were included. Extubation time was shorter in Gr: TCI, 15+/-2.6 vs.
      27.4+/-7.1 min in Gr: SA (P<0.001). The incidence of hypotension was higher in
      GrL: SA (P=0.009). Satisfaction was better in Gr: TCI (P=0.003). Antispasmodic
      need was higher in Gr: SA (P=0.023). Six patients in Gr: SA group had
      desaturation in post-anesthesia care unit (PACU) versus one patient from Gr: TCI
      (P=0.049). Patients in Gr: TCI had shorter PACU stay 40.2+/-7.3 vs. 58.7+/-12.4
      min (P<0.001). CONCLUSION: The use of TCI mode allows better optimization of
      general anesthesia technique during ERCP.

PMID- 27708523
TI  - Role of methylphenidate in the treatment of fatigue in advanced pancreatic cancer
      population.
AB  - BACKGROUND: Fatigue is a common but devastating symptom for advanced pancreatic
      cancer (APC) patients. To date, no proven treatment exists. Methylphenidate (MPH)
      showed inconsistent results in treating other cancer related fatigue. We
      performed a retrospective study to assess MPH in ameliorating fatigue in APC
      patients. METHODS: We retrospectively reviewed our clinic APC patients' records
      who visited from 06/2011 - 11/2014. Fatigue was assessed by Visual Analog Fatigue
      Scale (VAFS) and classified as grade 1 (VAFS 1-3), grade 2 (VAFS 4-6) and grade 3
      (VAFS 7-10) to correspond with CTCAE V4.0. MPH was dosed at 5 mg daily in the
      morning and was escalated to 10 mg after 2 weeks if needed. The primary endpoint
      was to assess the change of fatigue grade after 4 weeks of MPH. Secondary
      outcomes included MPH's effect on depression, anorexia, maintenance chemotherapy
      intensity and adverse effects. RESULTS: A total of 71 APC patients on concomitant
      chemotherapy were included, of whom 67% received doublet, 13% triplet, and 20%
      single-agent chemotherapy. Mean baseline VAFS was 7, which dropped to 4 after 4
      weeks of MPH, 55% patients' fatigue score improved by 1 grade, 8% by 2 grades,
      23% had fatigue resolved, 14% without benefit. 72% patients maintained
      chemotherapy intensity, 39% felt less depression and 52% had improved appetite.
      13% stopped MPH due to side effects. Rare Grade 3 or 4 adverse events included
      insomnia, restlessness, palpitations and anorexia. CONCLUSIONS: Our findings
      support low-dose MPH benefits APC patients with improved fatigue, depression and
      anorexia. A large randomized clinical trial is needed to confirm its usage and
      safety.

PMID- 27708525
TI  - Closure of large post-endoscopic submucosal dissection defects with lateral
      mucosal incisions and clips.

PMID- 27708526
TI  - Endoscopic submucosal dissection for anal intraepithelial neoplasia.

PMID- 27708527
TI  - A huge pancreatic mass.

PMID- 27708528
TI  - A new mechanism of gastroesophageal reflux in hiatal hernia documented by high
      resolution impedance manometry: a case report.
AB  - Gastroesophageal reflux disease (GERD) is recognized to be a multifactorial
      disease and several mechanisms leading to reflux have been described,
      nevertheless its pathophysiology has not been fully clarified. Hiatus hernia is a
      known risk factor for GERD since it impairs the esophagogastric junction, leading
      to: reduction in lower esophageal sphincter pressure; increase in the frequency
      of the transient lower esophageal sphincter relaxation; and impairment of
      esophageal clearance. Last generation diagnostic techniques have improved the
      understanding of these mechanisms. A 72-year-old woman with hiatus hernia and
      GERD underwent a high resolution impedance manometry (HRIM) after a partial
      response to treatment with pantoprazole. None of the proposed pathophysiological
      mechanisms for GERD could explain the presence of reflux: HRIM showed normal
      lower esophageal sphincter (LES) pressure and contractile integral, complete
      bolus clearance in all test swallows, and absence of transient LES relaxation.
      However, after the end of each peristaltic wave, as the LES pressure returned to
      resting values, a gastroesophageal reflux was detected until the following
      swallow. We describe an interesting case of a patient with a sliding hiatus
      hernia, with symptoms suggestive of GERD, in which HRIM revealed a new possible
      mechanism through which hiatus hernia may lead to GERD.

PMID- 27708529
TI  - Imatinib-induced hyperbilirubinemia with UGT1A1 (*28) promoter polymorphism:
      first case series in patients with gastrointestinal stromal tumor.
AB  - Imatinib, an orally administered protein-tyrosine kinase inhibitor (TKI) is
      indicated for the treatment of chronic myeloid leukemia (CML) and
      gastrointestinal stromal tumor (GIST). Severe hepatotoxicity associated with
      imatinib is rare, and relationship to polymorphism of uridine diphosphate
      glucuronosyltransferase 1A1 (UGT1A1) expression and related frequency of
      hyperbilirubinemia or toxicity are not well known. We present a case series
      patients who developed hyperbilirubinemia while on oral administration imatinib
      for treatment of GIST. Genetic testing for polymorphism of UGT1A1 showed the
      first patient to be homozygous for the UGT1A1 TA7 (*28) polymorphism and the
      second patient heterozygous for the UGT1A1 TA1 (*28) polymorphism. The first
      patient had to stop imatinib due to severe and persistent hyperbilirubenemia
      peaking >3 despite reducing imatininb to only 100 mg every other day while the
      second patient improved at this dose. Our case series represent the first data
      associating UGT1A1 polymorphism and imatinib in patients being treated for GIST.
      Given the prevalence of Gilbert's syndrome and the increasing use of imatinib, we
      encourage physicians to be aware of this possible toxicity as hepatotoxicity can
      be fatal if not managed in a timely fashion. This association is also timely due
      to recent FDA requirement for testing UGT1A1 polymorphism for nilotinib, another
      TKI.

PMID- 27708530
TI  - Esophageal location of mantle cell lymphoma.

PMID- 27708531
TI  - CALR mutation analysis is not indicated in patients with splanchnic vein
      thrombosis without evidence of a myeloproliferative neoplasm: a micro-review.

PMID- 27708533
TI  - Rice Bran Dietary Supplementation Improves Neurological Symptoms and Loss of
      Purkinje Cells in Vitamin E-Deficient Mice.
AB  - BACKGROUND: Vitamin E (VE, alpha-tocopherol) is a fat-soluble vitamin and is well
      known as an antioxidant. A deficiency in VE induces oxidative stress in the brain
      and causes motor and memory dysfunction. The consumption of a VE-rich diet has
      been given much attention in recent years, in regards to anti-aging and the
      prevention of age-related neuronal disorders. METHODS: A VE-deficient mouse model
      was prepared by feeding the animals a diet lacking VE. In addition, to evaluate
      the effect of VE-containing rice bran (RB) on VE deficiency, a diet including RB
      was also provided. VE levels in the brain tissue, as well as in the RB, were
      measured using an HPLC system. Behavioral tests, including rotarod, wheel running
      activity, Y-maze, and elevated plus maze were performed. To clarify the effect of
      VE deficiency and RB, we investigated the induction of heme oxygenase-1 (HO-1).
      Histological studies were performed using HE staining and immunohistochemical
      studies were performed using antibodies against glial fibrillary acidic protein
      (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1). RESULTS: VE in the
      mouse brain under a VE-deficient diet was decreased, and recovered alpha
      tocopherol levels were observed in the brain of mice fed an RB diet. Motor
      behavioral scores were decreased in VE-deficient conditions, while the
      supplementation of RB improved motor function. HO-1, a marker of oxidative
      stress, was upregulated in the mouse brain under VE deficiency, however, RB
      supplementation inhibited the increase of HO-1. Histological analyses showed
      neuronal degeneration of Purkinje cells and decreased GFAP-immunoreactivity of
      Bergmann glia in the cerebellum. In addition, activated astrocytes and microglia
      were observed in mice fed the VE-deficient diet. Mice fed the RB diet showed
      improvement in these histological abnormalities. CONCLUSION: A VE-deficient diet
      induced motor dysfunction in mice due to the degeneration of Purkinje cells in
      the cerebellum. Oral supplementation of RB increases VE in the brain and improved
      the motor dysfunction caused by VE deficiency. Thus, RB or unpolished rice may be
      a promising VE supplement.

PMID- 27708534
TI  - Qualitative Analysis of the Resilience of Adult Japanese Patients with Type 1
      Diabetes.
AB  - BACKGROUND: Resilience strategies are what we use to avoid and recover from
      error. In this study, we used the grounded theory approach to evaluate the
      resilience of Japanese patients with Type 1 diabetes. METHODS: Semi-structured
      interviews were conducted with 15 adults with Type 1 diabetes. Then, using
      grounded theory, we created a new model of resilience in this population.
      RESULTS: The results suggested a core category, "to make progress along the
      resilience path," comprising seven concepts classified into three stages. These
      seven concepts were as follows: "suffering from treatment," "damaged trust as a
      person," "persistence of afflictions," "awareness of supporters," "joy to be kept
      alive by insulin," "actively seeking a future," "being able to manage by
      oneself." Individuals with Type 1 diabetes used difficult experiences to motivate
      their resilience and to improve their situation. Additionally, resilience was an
      important contributor to these individuals' beliefs in their ability to face
      difficulties, to accept their illness and insulin therapy, and to control their
      illness. Resilience was also important to these individuals' faith in the future
      and in medical care. Our results are applicable to clinical care and research,
      such as the development of preventive interventions aimed at building or
      strengthening protective skills related to diabetes and its management.
      CONCLUSION: Ultimately, our goal is to equip adults with Type 1 diabetes with the
      tools to obtain sufficient behavioral and health-related resilience. Furthermore,
      these results highlight that maintaining resilience-related coping skills is
      important for adults and indicate that different psychological processes underlie
      resilience across the lifespan.

PMID- 27708535
TI  - R2* Map by IDEAL IQ for Acute Cerebral Infarction: Compared with Susceptibility
      Vessel Sign on T2*-Weighted Imaging.
AB  - BACKGROUND: To evaluate the detectability of arterial acute thrombus on R2* map
      by iterative decomposition of water and fat with echo asymmetry and least-squares
      estimation (IDEAL) IQ compared with T2*-weighted imaging (T2*WI). METHODS: Twenty
      six patients with acute cerebral infarction who underwent R2* map and T2*WI were
      reviewed. We performed visual assessment of each sequence regarding the
      visibility of susceptibility effect reflecting acute thrombus and quantitative
      evaluation of the thrombus on R2* map. RESULTS: Both R2* map and T2*WI showed
      susceptibility effect reflecting acute thrombi at the occluded site of magnetic
      resonance angiography (MRA) in 9 patients. R2* map revealed positive while T2*WI
      showed equivocal findings in 3 patients due to the surrounding vessel signal
      intensity. Acute thrombus at distal internal carotid artery (ICA) on R2* map was
      more clearly detected than that on T2*WI without any apparent susceptibility
      artifact from the skull base in 4 patients. Most of cardiogenic embolic
      infarction (CEI) and artery-to-artery embolic infarction (A-to-A) demonstrated
      positive and most of atherothrombotic infarction (ATI) revealed negative findings
      on R2* map, although quantitative R2* values of thrombi did not show significant
      differences between CEI (136.6 /msec) and A-to-A (189.9 /msec) (P = 0.332).
      CONCLUSION: The detectability of acute thrombus on R2* map is comparable to that
      on T2*WI. Regarding thrombus at distal ICA, its detectability on R2* map is
      superior to that on T2*WI. R2* map provide additional information to distinguish
      between embolic and atherothrombotic infarctions.

PMID- 27708532
TI  - Synthesis and spectroscopic properties of beta,beta'-dibenzo-3,5,8-triaryl
      BODIPYs.
AB  - A series of beta,beta'-bicyclo-3,5-diaryl-BODIPYs were synthesized from the
      corresponding beta,beta'-bicyclo-3,5-diiodo-BODIPYs (1a,b) via Pd(0)-mediated
      Suzuki cross-coupling reactions in 82-92% yields. Subsequent aromatization with
      DDQ afforded the corresponding beta,beta'-dibenzo-aryl-BODIPYs, which showed red
      shifted absorptions and emissions in the near-IR range. The dibenzo-appended
      BODIPYs showed characteristic 1H-, 13C-, 11B- and 19F-NMR shifts, and nearly
      planar conformations by X-ray crystallography.

PMID- 27708537
TI  - Construction and Evaluation of Cytomegalovirus DNA Quantification System with
      Real-Time Detection Polymerase Chain Reaction.
AB  - BACKGROUND: For patients with reactivation of human cytomegalovirus (CMV), a
      highly sensitive and accurate CMV quantification system is essential to monitor
      viral load. METHODS: We constructed a real-time detection PCR (RTD-PCR) system
      for CMV DNA and evaluated its linearity, lower detection limit, dynamic range and
      accuracy using two CMV standards. We used 219 clinical samples derived from 101
      patients to compare the system with the pp65 antigen test. RESULTS: The 95%
      detection limit was determined to be 556 IU/mL (95% CI, 440-797 IU/mL), and the
      quantification range was between 102 and 106 copies or IU/mL (r = 0.996, 0.999,
      respectively). The coefficients of variation of inter-assay reproducibility
      assessed in each three different runs were 2.5% at 1,000 IU/mL and 1.6% at 10,000
      IU/mL. The coefficients of variation of intra-assay variability by testing the
      same samples three times in a single run were 1.8-3.6% and 0.4-1.9%,
      respectively. The concordance between antigenemia and plasma or serum CMV DNA
      levels was a good correlation (r = 0.695, P < 0.01). CONCLUSION: We constructed
      the RTD-PCR system which enables accurate evaluation of CMV reactivation by
      monitoring of viral load in immunosuppressed or immunocompromised patients.

PMID- 27708536
TI  - Intra-Abdominal Complications after Curative Gastrectomies Worsen Prognoses of
      Patients with Stage II-III Gastric Cancer.
AB  - BACKGROUND: Postoperative complications have been shown to worsen prognoses of
      various cancer types. METHODS: We retrospectively analyzed 265 patients with
      stage II-III gastric cancer who underwent curative gastrectomies between 1991 and
      2010 at Tottori University Hospital to determine the effect of postoperative
      intra-abdominal complication (IAC) on prognosis. RESULTS: Of the 265 patients, 38
      (14.3%) developed postoperative IACs of grade >= 2, of whom significantly more
      patients were male. Patients in the IAC group were significantly older than
      patients in the non-complication (NC) group. The NC group had significantly
      better survival than did the IAC group (P < 0.0001). Within the IAC group, 5-year
      survival rates did not significantly differ between patients with infectious
      complication subgroup (24.6%) and the non-infectious subgroup (46.2%). Grade of
      complication was not related to prognosis. Lengths of time before starting
      adjuvant chemotherapy (AC) after surgery were significantly longer for the IAC
      group (55.3 +/- 34.7 days) than for the NC group: (26.6 +/- 11.9 days; P =
      0.0023). Prognosis of patients who took AC within 6 weeks after surgery tended to
      be better than that of patients who took AC > 6 weeks after surgery (P = 0.071).
      In multivariate analysis, IAC was an independent predictor of prognosis, as were
      age, invasion depth, and lymph node metastasis. CONCLUSION: Postoperative IACs
      were related to poorer survival for patients with stage II-III gastric cancer.

PMID- 27708538
TI  - Preconditioning by Low Dose LPS Prevents Subsequent LPS-Induced Severe Liver
      Injury via Nrf2 Activation in Mice.
AB  - BACKGROUND: Sepsis is a syndrome triggered by endotoxin lipopolysaccharide (LPS)
      during bacterial infection. Sepsis sometimes recurs, with the second sepsis
      giving rise to a different phenotype because of disease modification by the
      preceding sepsis. Such a protective modification is called a preconditioning (PC)
      effect. PC is an endogenous protective mechanism by which sublethal damage
      confers tolerance to a subsequent lethal load. Oxidative stress is one of the
      important pathogenetic mechanisms that occur in sepsis. The nuclear factor
      erythroid 2 (NF-E2)-related factor-2 (Nrf2) system is a key regulatory
      transcription factor that protects organs and cells against oxidative stress and
      may be associated with the PC effect in repeated sepsis. METHODS: The effect of
      PC induced by low-dose LPS on survival rate and liver injury against subsequent
      high-dose LPS stimulation was examined using a mouse model of sepsis. In order to
      understand the detailed mechanism(s) involved in the PC effect within the liver,
      gene expression array was performed. As a candidate mechanism of PC, the
      activation of the Nrf2 system was analyzed using Nrf2 reporter mice. Furthermore,
      the induction of heme oxygenase-1 (HO-1), one of the main targets of Nrf2, in the
      liver was examined by immunoblotting and immunohistochemistry. The PC effect on
      liver injury induced by LPS was further examined using Nrf2-deficient mice.
      RESULTS: PC by LPS (1.7 or 5.0 mg/kg body weight, intraperitoneally) increased
      the survival rate of mice and decreased liver injury in response to a subsequent
      injection of a lethal level of LPS (20 mg/kg body weight). DNA array revealed
      that the gene ontology term "antioxidant activity" as one of the candidate
      mechanisms of the PC effect by LPS. In Nrf2 reporter mice, PC immediately and
      intensely enhanced luminescence that indicated Nrf2 activation after subsequent
      LPS injection. The induction of HO-1 by LPS was also enhanced by preceding PC,
      and its induction was observed mainly in Kupffer cells of the liver. In Nrf2
      deficient mice, the induction of HO-1 in Kupffer cells and the hepatoprotective
      effect of PC were decreased as compared with wild-type mice. CONCLUSION: Our
      results suggest that activation of the Nrf2 system is, at least in part, one of
      the mechanisms of a PC effect in the mouse liver in the case of repeated LPS
      stimulation.

PMID- 27708539
TI  - Usefulness of T-Shaped Gauze for Precise Dissection of Supra-Pancreatic Lymph
      Nodes and for Reduced Postoperative Pancreatic Fistula in Patients Undergoing
      Laparoscopic Gastrectomy for Gastric Cancer.
AB  - BACKGROUND: Supra-pancreatic lymph node dissection is important in patients
      undergoing laparoscopic gastrectomy (LG) for gastric cancer. A clear view of the
      supra-pancreatic area is necessary for precise dissection of supra-pancreatic
      lymph nodes without injury to the pancreas. This retrospective study assessed the
      efficacy of T-shaped gauze (TSG) in retracting the pancreas during supra
      pancreatic lymph node dissection. METHODS: The study cohort consisted of 80
      patients who underwent LG for gastric cancer. Of these, 44 patients underwent
      pancreatic retraction with TSG (TSG group) and 36 without TSG (non-TSG group).
      The efficacy of TSG for pancreatic retraction was evaluated by comparing all
      grade and Clavien-Dindo grade >= III postoperative pancreatic fistula (POPF) and
      the total number of dissected supra-pancreatic lymph nodes in the TSG and non-TSG
      groups. RESULTS: The rates of all grade (6.8% vs. 11%) and of Clavien-Dindo grade
      >= III (2.2% vs. 5.5%) POPF were lower in the TSG than in the non-TSG group. The
      total number of supra-pancreatic lymph nodes harvested by Dissection 1+ (D1+)
      lymph node dissection was significantly higher in TSG than in non-TSG patients (P
      = 0.0078). CONCLUSION: TSG may be useful for safe and efficient performance of
      supra-pancreatic lymph node dissection.

PMID- 27708540
TI  - Combination Therapy of Interventional Radiology and Surgery for Infarction of the
      Small Intestine Caused by Portal Vein and Mesenteric Vein Thrombosis: A Patient
      Report.
AB  - We report the case of a man in his 70s who suffered from intestinal infarction
      caused by acute portal vein and mesenteric vein thrombosis (PVMVT). Combination
      therapy with percutaneous transcatheter thrombectomy and surgical bowel resection
      was successfully performed, and a satisfactory outcome was achieved. Intestinal
      infarction caused by PVMVT can be fatal and has a high mortality rate even if
      surgical resection is performed. The combination therapy of interventional
      radiology and surgery might be a safe and effective method for patients with this
      life-threatening condition.

PMID- 27708541
TI  - Analysis of Direct Simultaneous Measurement of Glottal Airflow Velocity,
      Subglottal Pressure, and High-Speed Imaging Using Flexible Transnasal Endoscope
      in a Human Subject.
AB  - It is difficult to directly observe glottal airflow velocity just above the
      glottis due to sensor size requirements and limited accessibility. We developed a
      miniature hot-wire probe and flexible fiberscopic high-speed imaging system for
      human examinations. Simultaneous direct measurement of glottal airflow velocity,
      subglottal pressure, and vocal fold vibration was achieved in a patient who was
      treated with a T-tube for tracheal stenosis. Airflow velocity changes at the
      anterior midline of the vocal folds were synchronized with subglottal pressure
      changes during each phonation cycle. The velocity at the anterior midline of the
      vocal folds showed a rhythmic pattern of sharp, high peaks. The result of fast
      Fourier transform analysis indicated that glottal velocity at the anterior
      midline of the vocal folds had abundant high-frequency components that were not
      affected by resonance of the vocal tract. Airflow velocity was variable and
      diminished except at the anterior midline of the vocal folds.

PMID- 27708542
TI  - Atypical Arteritis in Internal Carotid Arteries: A Novel Concept of Isolated
      Internal Carotid Arteritis.
AB  - We presented a 38-year-old woman suffering from acute cerebral infarction due to
      arteritis limited to bilateral internal carotid arteries without a condition of
      giant cell arteritis or granulomatosis with polyangitis. Our case is
      unprecedented and characterized by a young woman with wall enhancement in the
      internal carotid arteries on contrast-enhanced magnetic resonance imaging (MRI),
      therapeutic effects of steroids, and positive status for human leucocyte antigen
      B39, -B51 and -DR4. These disease characteristics were not in accordance with
      existing diagnostic criteria of vasculitis, such as Takayasu's arteritis, giant
      cell arteritis, granulomatosis with polyangiitis, and Behcet's disease. We
      suggested consideration of a novel "isolated internal carotid arteritis" disease
      concept.

PMID- 27708544
TI  - Justice-based social assistance.
AB  - What are the main objectives of social protection institutions in developing
      countries? What should be their scope and reach? What is the source of their
      legitimacy? Finding appropriate answers to these questions is essential to
      understanding, and shaping, the emergence of welfare institutions in low- and
      middle-income countries. Most available answers rely on instrumental arguments.
      Few make reference to normative principles. This article draws on three concepts
      from Rawls - social justice as regulating cooperation, the social minimum, and
      the need for a freestanding political notion of social justice - to develop a
      coherent argument for grounding social assistance on social justice. In line with
      this argument, it identifies some parameters for a justice-based social
      assistance. This article then discusses, with examples, the tensions existing
      between a social justice-based social minimum and 'real' social assistance
      institutions emerging in developing countries.

PMID- 27708543
TI  - Molecular basis of human cerebral malaria development.
AB  - Cerebral malaria is still a deleterious health problem in tropical countries. The
      wide spread of malarial drug resistance and the lack of an effective vaccine are
      obstacles for disease management and prevention. Parasite and human genetic
      factors play important roles in malaria susceptibility and disease severity. The
      malaria parasite exerted a potent selective signature on the human genome, which
      is apparent in the genetic polymorphism landscape of genes related to
      pathogenesis. Currently, much genomic data and a novel body of knowledge,
      including the identification of microRNAs, are being increasingly accumulated for
      the development of laboratory testing cassettes for cerebral malaria prevention.
      Therefore, understanding of the underlying complex molecular basis of cerebral
      malaria is important for the design of strategy for cerebral malaria treatment
      and control.

PMID- 27708545
TI  - Chromosomal abnormality of acute promyelocytic leukemia other than PML-RARA: a
      case report of acute promyelocytic leukemia with del(5q).
AB  - BACKGROUND: The recent study described a better outcome in acute promyelocytic
      leukemia patients treated with all-trans retinoic acid and arsenic oxide compared
      to those treated with all-trans retinoic acid combined with conventional
      chemotherapy. The pivotal study indicated that favorable-risk acute promyelocytic
      leukemia patients can be cured without any cytotoxic chemotherapy. Even high-risk
      patients are treatable with cytotoxic agents. Acute promyelocytic leukemia does
      not develop only by the dedifferentiation caused by PML-RARA. A determined
      oncogene other than PML-RARA which promotes cell proliferation would be required.
      CASE PRESENTATION: We recently treated a 30-year-old Japanese female who achieved
      molecular remission with only the administration of all-trans retinoic acid. The
      patient's leukemic clones concomitantly had a del(5q) aberrant chromosome with
      t(15;17) (q22;q12). The patient's bone marrow cells indicated clonal evolution of
      the tumor cells expressing CD13dim, CD33+, CD117+, and lacking HLA-DR, CD34 and
      CD11b. A fluorescence in situ hybridization analysis detected PML-RARA fusion
      genes in the patient's bone marrow specimens, leading to the diagnosis of acute
      promyelocytic leukemia. CONCLUSION: A del(5q) is one of the characteristic
      chromosomal abnormalities observed in myelodysplastic syndrome. On the other
      hand, up to 40 % of acute promyelocytic leukemia cases are known to harbor the
      addition of a clonal cytogenetic abnormality. However, such a case acute
      promyelocytic leukemia with del(5q) would be rare, rather than myelodysplastic
      syndrome, consequently obtaining t(15;17). Which cytogenetic abnormalities, acute
      promyelocytic leukemia or myelodysplastic syndrome, came first is informative to
      make a clinical decision for the initial therapy. In this case, we speculated the
      PML-RARA translocation is an original pathogenesis and thereafter additional
      cytogenetic abnormalities (del(5q) and -6) common in myelodysplastic syndrome.
      All-trans retinoic acid lead the patient into molecular remission. We propose
      that an assessment of additional cytogenetic abnormality in acute promyelocytic
      leukemia would contribute to the clinical decisions regarding whether to treat
      disease with all-trans retinoic acid and cytotoxic agents. It would be of
      interest to know the extent of cytogenetic abnormality in the patients regarding
      to mixed leukemia. One or more additional cytogenetic abnormalities other than
      PML-RARA could account for the biological malignant grade and prognostic index.

PMID- 27708546
TI  - The impact of occupational stress on nurses' caring behaviors and their health
      related quality of life.
AB  - BACKGROUND: Nursing is perceived as a strenuous job. Although past research has
      documented that stress influences nurses' health in association with quality of
      life, the relation between stress and caring behaviors remains relatively
      unexamined, especially in the Greek working environment, where it is the first
      time that this specific issue is being studied. The aim was to investigate and
      explore the correlation amidst occupational stress, caring behaviors and their
      quality of life in association to health. METHODS: A correlational study of
      nurses (N = 246) who worked at public and private units was conducted in 2013 in
      Greece. The variables were operationalized using three research instruments: (1)
      the Expanded Nursing Stress Scale (ENSS), (2) the Health Survey SF-12 and (3) the
      Caring Behaviors Inventory (CBI). Univariate and multivariate analyses were
      performed. RESULTS: Contact with death, patients and their families, conflicts
      with supervisors and uncertainty about the therapeutic effect caused
      significantly higher stress among participants. A significant negative
      correlation was observed amidst total stress and the four dimensions of CBI.
      Certain stress factors were significant and independent predictors of each CBI
      dimension. Conflicts with co-workers was revealed as an independent predicting
      factor for affirmation of human presence, professional knowledge and skills and
      patient respectfulness dimensions, conflicts with doctors for respect for
      patient, while conflicts with supervisors and uncertainty concerning treatment
      dimensions were an independent predictor for positive connectedness. Finally,
      discrimination stress factor was revealed as an independent predictor of quality
      of life related to physical health, while stress resulting from conflicts with
      supervisors was independently associated with mental health. CONCLUSION:
      Occupational stress affects nurses' health-related quality of life negatively,
      while it can also be considered as an influence on patient outcomes.

PMID- 27708547
TI  - Life is determined by its environment.
AB  - A well-developed theory of evolutionary biology requires understanding of the
      origins of life on Earth. However, the initial conditions (ontology) and causal
      (epistemology) bases on which physiology proceeded have more recently been called
      into question, given the teleologic nature of Darwinian evolutionary thinking.
      When evolutionary development is focused on cellular communication, a distinctly
      different perspective unfolds. The cellular communicative-molecular approach
      affords a logical progression for the evolutionary narrative based on the basic
      physiologic properties of the cell. Critical to this appraisal is recognition of
      the cell as a fundamental reiterative unit of reciprocating communication that
      receives information from and reacts to epiphenomena to solve problems. Following
      the course of vertebrate physiology from its unicellular origins instead of its
      overt phenotypic appearances and functional associations provides a robust,
      predictive picture for the means by which complex physiology evolved from
      unicellular organisms. With this foreknowledge of physiologic principles, we can
      determine the fundamentals of Physiology based on cellular first principles using
      a logical, predictable method. Thus, evolutionary creativity on our planet can be
      viewed as a paradoxical product of boundary conditions that permit homeostatic
      moments of varying length and amplitude that can productively absorb a variety of
      epigenetic impacts to meet environmental challenges.

PMID- 27708548
TI  - KIAA0101, a target gene of miR-429, enhances migration and chemoresistance of
      epithelial ovarian cancer cells.
AB  - BACKGROUND: Ovarian cancer is a common type of gynecological malignancies, and is
      the fifth leading cause of cancer-related death in women in the United States.
      MiR-429 and KIAA0101 have been found to be involved in several human
      malignancies, respectively. However, the role of miR-429 and KIAA0101, and the
      correlation between them during development of epithelial ovarian cancer (EOC)
      remain to be investigated. METHODS: The expression of KIAA0101 in EOC tissues and
      cells was measured by Quantitative real-time PCR, western blot, and
      immunochemistry. Cell proliferation assay, colony formation assay, and transwell
      assay was performed to assess the role of miR-429 and KIAA0101 in regulation of
      proliferation, migration, and chemoresistance of EOC cells. Luciferase assay was
      used to test the Wnt/beta-catenin signaling activity in response to depletion of
      KIAA0101 and overexpression of miR-429. RESULTS: We found that KIAA0101 was
      upregulated in metastatic EOC tissues, compared to primary EOC tissues, and
      KIAA0101 was required for the migration activity and chemoresistance of EOC cells
      by enhancing Wnt/beta-catenin signaling. Furthermore, we revealed KIAA0101 is
      direct target of miR-429. Similar to knockdown of KIAA0101, overexpression of miR
      429 reduced invasion and chemoresistance of EOC cells. Co-transfection of
      KIAA0101 partially abrogates the inhibitory effects on invasion and
      chemoresistance in EOC cells. CONCLUSIONS: KIAA0101, a target gene of miR-429,
      was upregulated in the metastatic EOC tissues, and enhanced the migration
      activity and chemoresistance of EOC cells. Both miR-429 and KIAA0101 may
      represent the potential therapeutic targets of EOC.

PMID- 27708549
TI  - Success of tumorsphere isolation from WHO grade IV gliomas does not correlate
      with the weight of fresh tumor specimens: an immunohistochemical characterization
      of tumorsphere differentiation.
AB  - BACKGROUND: A trend of stage-by-stage increase in tumorsphere (TS) formation from
      glioma samples has been reported. Despite this trend, not all surgical specimens
      give rise to TSs, even World Health Organization (WHO) grade IV gliomas.
      Furthermore, it has been reported that differences in overall survival of primary
      glioblastoma patients depends on the propensity of their tumors to form TSs.
      However, the weights of fresh specimens vary from one surgical isolate to the
      next. METHODS: Accordingly, we evaluated the relationship between the weights of
      surgical specimens in WHO grade IV gliomas with the capacity to isolate TSs.
      Thirty-five fresh WHO grade IV glioma specimens were separated into two groups,
      based on whether they were positive or negative for TS isolation, and the
      relationship between TS isolation and weight of surgical specimens was assessed.
      RESULTS: We observed no significant difference in the weights of surgical samples
      in the two groups, and found that the optimal weight of specimens for TSs
      isolation was 500 mg. CONCLUSION: Thus, contrary to our expectations, the ability
      to isolate TSs from WHO grade IV glioma specimens was not related to the weight
      of fresh specimens.

PMID- 27708550
TI  - Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and
      in vitro study.
AB  - OBJECTIVE: To explore the relationship between tumor necrosis factor receptor
      associated factor 6 (TRAF6) and the clinicopathological features in HCC as well
      as its biological function. METHODS: Totally, 412 liver tissues were collected,
      including 171 hepatocellular carcinoma (HCC) and their corresponding non-tumor
      tissues, 37 cirrhosis and 33 normal liver tissues. The expression of TRAF6 was
      assessed by immunohistochemistry. Then, analysis of the correlations between
      TRAF6 expression and clinicopathological parameters in HCC was conducted.
      Furtherer, in vitro experiments on HepG2 and Hep3B cells were performed to
      validate the biological function of TRAF6 on HCC cells. TRAF6 siRNA was
      transfected into HepG2 and Hep3B cell lines and TRAF6 expression was evaluated
      with RT-qPCR and western blot. The assays of cell viability, proliferation,
      apoptosis and caspase-3/7 activity were carried out to investigate the effects of
      TRAF6 on HCC cells with RNA interference. Cell viability was assessed with Cell
      Titer-Blue kit. Cell proliferation was tested with MTS kit. Cell apoptosis was
      checked through morphologic detection with fluorescence microscope, as well as
      caspase-3/7 activity was measured with fluorogenic substrate detection. RESULTS:
      The positive expression rate of TRAF6 protein was 49.7 % in HCC, significantly
      higher than that of normal liver (12.1 %), cirrhosis (21.6 %) and adjacent non
      cancerous tissues (36.3 %, all P < 0.05). Upregulated TRAF6 was detected in
      groups with metastasis (Z = -2.058, P = 0.04) and with low micro-vessel density
      (MVD) expression (Z = -2.813, P = 0.005). Spearman correlation analysis further
      showed that the expression of TRAF6 was positively correlated with distant
      metastasis (r = 0.158, P = 0.039) and negatively associated with MVD (r = -0.249,
      P = 0.004). Besides, knock-down of TRAF6 mRNA in HCC cell lines HepG2 and Hep3B
      both resulted in cell viability and proliferation inhibition, also cell apoptosis
      induction and caspase-3/7 activity activation. CONCLUSIONS: TRAF6 may contribute
      to metastasis and deterioration of the HCC via influencing cell growth and
      apoptosis. Thus, TRAF6 might become a predictive and therapeutic biomarker for
      HCC.

PMID- 27708551
TI  - Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances
      chemosensitivity of human colon cancer cells.
AB  - BACKGROUND: Molecular profiling of colorectal cancer (CRC) based on global gene
      expression has revealed multiple dysregulated signalling pathways associated with
      drug resistance and poor prognosis. However, the role of BMP2 signaling in CRC is
      not fully characterised. METHODS: Bioinformatics data analysis were conducted on
      the GSE21510 dataset. Leniviral technology was utilized to stably express BMP2 in
      the HCT116 CRC model. Gene expression profiling was conducted using Agilent
      microarray platform while data normalization and bioinformatics were conducted
      using GeneSpring software. Changes in gene expression were assessed using qRT
      PCR. AlamarBlue assay was used to assess cell viability in vitro. In vivo
      experiments were conducted using SCID mice. RESULTS: Our data revealed frequent
      downregulation of BMP2 in primary CRC tissues. Additionally, interrogation of
      publically available gene expression datasets revealed significant downregulation
      of BMP2 in metastatic recurrent compared to non-metastatic cancer (p = 0.02).
      Global gene expression analysis in CRC cells over-expressing BMP2 revealed
      multiple dysregulated pathways mostly affecting cell cycle and DNA damage
      response. Concordantly, lentiviral-mediated re-expression of BMP2 inhibited
      HCT116 CRC growth, sphere formation, clonogenic potential, cell migration, and
      sensitized CRC cells to 5-fluorouracil (5-FU) in vitro. Additionally, BMP2
      inhibited CRC tumor formation in SCID mice. CONCLUSIONS: Our data revealed an
      inhibitory role for BMP2 in CRC, suggesting that restoration of BMP2 expression
      could be a potential therapeutic strategy for CRC.

PMID- 27708552
TI  - Burden of allergic respiratory disease: a systematic review.
AB  - This meta-analysis compared the health-related quality of life (HRQL) of patients
      with allergic rhinitis (AR) and/or allergic asthma (AA) caused by perennial house
      dust mite (HDM) versus AR and/or AA caused by seasonal pollen allergy. Following
      a systematic search, the identified studies used the disease-specific rhinitis
      quality of life questionnaire or generic instruments (SF-36 and SF-12). Summary
      estimates obtained by meta-analysis showed that HRQL in patients with perennial
      HDM allergy was significantly worse than that of patients with seasonal pollen
      allergy, when measured by both disease-specific and generic HRQL instruments, and
      was reflected by an impact on both physical and mental health. A systematic
      review of cost data on AR and AA in selected European countries demonstrated that
      the majority of the economic burden was indirectly caused by high levels of
      absenteeism and presenteeism; there was little or no evidence of increasing or
      decreasing cost trends. Increased awareness of the detrimental effects of AR
      and/or AA on patients' HRQL and its considerable cost burden might encourage
      early diagnosis and treatment, in order to minimize the disease burden and ensure
      beneficial and cost-effective outcomes.

PMID- 27708554
TI  - Individually optimized stereotactic radiotherapy for pancreatic head tumors: A
      planning feasibility study.
AB  - AIM: Aim of this study was to perform a planning feasibility analysis of a 3
      level dose prescription using an IMRT-SIB technique. BACKGROUND: Radiation
      therapy of locally advanced pancreatic cancer should administer a minimum dose to
      the duodenum and a very high dose to the vascular infiltration areas to improve
      the possibility of a radical resection. MATERIALS AND METHODS: Fifteen patients
      with pancreatic head adenocarcinoma and vascular involvement were included. The
      duodenal PTV (PTVd) was defined as the GTV overlapping the duodenal PRV. Vascular
      CTV (CTVv) was defined as the surface of contact or infiltration between the
      tumor and vessel plus a 5 mm margin. Vascular PTV (PTVv) was considered as the
      CTVv plus an anisotropic margin. The tumor PTV (PTVt) was defined as the GTV plus
      a margin including the PTVv and excluding the PTVd. The following doses were
      prescribed: 30 Gy (6 Gy/fraction) to PTVd, 37.5 Gy (7.5 Gy/fraction) to PTVt, and
      45 Gy (9 Gy/fraction) to PTVv, respectively. Treatment was planned with an IMRT
      technique. RESULTS: The primary end-point (PTVv Dmean > 90%) was achieved in all
      patients. PTVv D98% > 90% was achieved in 6 patients (40%). OARs constraints were
      achieved in all patients. CONCLUSIONS: Although the PTVv D95% > 95% objective was
      achieved only in 40% of patients, the study showed that in 100% of patients it
      was possible to administer a strongly differentiated mean/median dose.
      Prospective trials based on clinical application of this strategy seem to be
      justified in selected patients without overlap between PTVd and PTVv.

PMID- 27708553
TI  - Proposal for new diagnostic criteria for DIC from the Japanese Society on
      Thrombosis and Hemostasis.
AB  - Disseminated intravascular coagulation (DIC) is a serious disease that, in the
      presence of underlying disease, causes persistent, generalized, marked
      coagulation activation. Early treatment based on an appropriate diagnosis is very
      important for improving patients' prognosis, to which end diagnostic criteria
      play a key role. Several criteria have been proposed, but each has its strengths
      and weaknesses, and improved criteria are needed. Widespread use of
      coagulofibrinolytic markers has elucidated that the pathology of DIC differs
      greatly as a function of the underlying disease. Thus, discriminating use of DIC
      diagnostic criteria that take underlying diseases into account is important. DIC
      diagnostic criteria that are well known in Japan include the Japanese Ministry of
      Health and Welfare's old DIC diagnostic criteria (JMHW criteria), the
      International Society on Thrombosis and Haemostasis's DIC diagnostic criteria
      (ISTH criteria), and the Japanese Association for Acute Medicine's acute-stage
      DIC diagnostic criteria (JAAM criteria). Those criteria have their respective
      drawbacks: the sensitivity of the ISTH criteria is poor, the JAAM criteria cannot
      be applied to all underlying diseases, and the JMHW criteria have poor
      sensitivity in the case of infections, do not use molecular markers, and result
      in misdiagnosis. The Japanese Society on Thrombosis and Hemostasis's newly
      proposed provisional draft DIC diagnostic criteria (new criteria) use diagnostic
      criteria classifications of "hematopoietic disorder type", "infectious type", and
      "basic type" based on the underlying pathology. For the hematopoietic disorder
      type the platelet count is omitted from the score, while for the infectious type,
      fibrinogen is omitted from the score. Also, points are added if the platelet
      count decreases with time. In the new criteria, molecular markers and
      antithrombin activity have been newly included, and as a countermeasure for
      misdiagnosis, 3 points are deducted if there is liver failure. In this paper, we
      discuss various problems encountered with DIC diagnosis, and we describe the new
      criteria together with the events that led to their creation. These new
      diagnostic criteria take into account the underlying diseases of wide area, and
      we expect that they will serve clinicians well due to the above adaptations and
      improvements.

PMID- 27708555
TI  - The Impact of School Social Support and Bullying Victimization on Psychological
      Distress among California Adolescents.
AB  - BACKGROUND AND PURPOSE: National reports showed that over 20% of high school
      students were victims of bullying, which could potentially lead to psychological
      problems. School social support may be protective against mental distress linked
      with victimization. This study examined the main and moderating effects of social
      support from adults in schools on non-specific serious psychological distress
      (SPD) related to victimization among California adolescents. METHODS: Utilizing
      the 2011-2012 California Health Interview Survey (CHIS), we analyzed a
      representative sample of 2,799 adolescents aged 12-17 years old. Logistic
      regression analyses were conducted modeling the odds of SPD in relation to school
      social support and victimization. RESULTS: Adolescents who were victimized were
      twice as likely to have SPD compared to non-victims. Higher level of social
      support from adults in schools was protective against SPD, but did not buffer the
      effect of bullying exposure. DISCUSSION: Findings from the present study
      suggested that adult support from schools can help with students' psychological
      problems but does not appear to prevent the psychological consequences of
      victimization. Additional intervention is needed, above and beyond social
      support, to prevent victimization and its psychological consequences.

PMID- 27708556
TI  - Precision medicine: from pharmacogenomics to pharmacoproteomics.
AB  - Disease progression and drug response may vary significantly from patient to
      patient. Fortunately, the rapid development of high-throughput 'omics'
      technologies has allowed for the identification of potential biomarkers that may
      aid in the understanding of the heterogeneities in disease development and
      treatment outcomes. However, mechanistic gaps remain when the genome or the
      proteome are investigated independently in response to drug treatment. In this
      article, we discuss the current status of pharmacogenomics in precision medicine
      and highlight the needs for concordant analysis at the proteome and metabolome
      levels via the more recently-evolved fields of pharmacoproteomics,
      toxicoproteomics, and pharmacometabolomics. Integrated 'omics' investigations
      will be critical in piecing together targetable mechanisms of action for both
      drug development and monitoring of therapy in order to fully apply precision
      medicine to the clinic.

PMID- 27708557
TI  - Plasma degradome affected by variable storage of human blood.
AB  - BACKGROUND: The successful application of-omics technologies in the discovery of
      novel biomarkers and targets of therapeutic interventions is facilitated by large
      collections of well curated clinical samples stored in bio banks. Mining the
      plasma proteome holds promise to improve our understanding of disease mechanisms
      and may represent a source of biomarkers. However, a major confounding factor for
      defining disease-specific proteomic signatures in plasma is the variation in
      handling and processing of clinical samples leading to protein degradation. To
      address this, we defined a plasma proteolytic signature (degradome) reflecting
      pre-analytical variability in blood samples that remained at ambient temperature
      for different time periods after collection and prior to processing. METHODS: We
      obtained EDTA blood samples from five healthy volunteers (n = 5), and blood tubes
      remained at ambient temperature for 30 min, 8, 24 and 48 h prior to
      centrifugation and isolation of plasma. Naturally occurred peptides derived from
      plasma samples were compared by label-free quantitative LC-MS/MS. To profile
      protein degradation, we analysed pooled plasma samples at T = 30 min and 48 h
      using PROTOMAP analysis. The proteolytic pattern of selected protein candidates
      was further validated by immunoblotting. RESULTS: A total of 820 plasma proteins
      were surveyed by PROTOMAP, and for 4 % of these, marked degradation was observed.
      We show distinct proteolysis patterns for talin-1, coagulation factor XI,
      complement protein C1r, C3, C4 and thrombospondin, and several proteins including
      S100A8, A9, annexin A1, profiling-1 and platelet glycoprotein V are enriched
      after 48 h blood storage at ambient temperature. In particular, thrombospondin
      protein levels increased after 8 h and proteolytic fragments appeared after 24 h
      storage time. CONCLUSIONS: The overall impact of blood storage at ambient
      temperature for variable times on the plasma proteome and degradome is relatively
      minor, but in some cases can cause a potential bias in identifying and assigning
      relevant proteomic markers. The observed effects on the plasma proteome and
      degradome are predominantly triggered by limited leucocyte and platelet cell
      activation due to blood handling and storage. The baseline plasma degradome
      signature presented here can help filtering candidate protein markers relevant
      for clinical biomarker studies.

PMID- 27708558
TI  - Erratum to: Chinese smokers' behavioral response toward cigarette price:
      individual and regional correlates.
AB  - [This corrects the article DOI: 10.1186/s12971-016-0078-7.].

PMID- 27708559
TI  - Does Prenatal Valproate Interact with a Genetic Reduction in the Serotonin
      Transporter? A Rat Study on Anxiety and Cognition.
AB  - There is ample evidence that prenatal exposure to valproate (or valproic acid,
      VPA) enhances the risk of developing Autism Spectrum Disorders (ASD). In line
      with this, a single injection of VPA induces a multitude of ASD-like symptoms in
      animals, such as rats and mice. However, there is equally strong evidence that
      genetic factors contribute significantly to the risk of ASD and indeed, like most
      other psychiatric disorders, ASD is now generally thought to results from an
      interaction between genetic and environmental factors. Given that VPA
      significantly impacts on the serotonergic system, and serotonin has strong
      biochemical and genetic links to ASD, we aimed to investigate the interaction
      between genetic reduction in the serotonin transporter and prenatal valproate
      administration. More specifically, we exposed both wildtype (SERT+/+) rats and
      rats heterozygous for the serotonin transporter deletion (SERT+/-) to a single
      injection of 400 mg/kg VPA at gestational day (GD) 12. The offspring, in
      adulthood, was assessed in four different tests: Elevated Plus Maze and Novelty
      Suppressed Feeding as measures for anxiety and prepulse inhibition (PPI) and
      latent inhibition as measures for cognition and information processing. The
      results show that prenatal VPA significantly increased anxiety in both paradigm,
      reduced PPI and reduced conditioning in the latent inhibition paradigm. However,
      we failed to find a significant gene-environment interaction. We propose that
      this may be related to the timing of the VPA injection and suggest that whereas
      GD12 might be optimal for affecting normal rat, rats with a genetically
      compromised serotonergic system may be more sensitive to VPA at earlier time
      points during gestation. Overall our data are the first to investigate gene *
      environmental interactions in a genetic rat model for ASD and suggest that timing
      may be of crucial importance to the long-term outcome.

PMID- 27708560
TI  - Targeted Re-Sequencing Approach of Candidate Genes Implicates Rare Potentially
      Functional Variants in Tourette Syndrome Etiology.
AB  - Although the genetic basis of Tourette Syndrome (TS) remains unclear, several
      candidate genes have been implicated. Using a set of 382 TS individuals of
      European ancestry we investigated four candidate genes for TS (HDC, SLITRK1,
      BTBD9, and SLC6A4) in an effort to identify possibly causal variants using a
      targeted re-sequencing approach by next generation sequencing technology.
      Identification of possible disease causing variants under different modes of
      inheritance was performed using the algorithms implemented in VAAST. We
      prioritized variants using Variant ranker and validated five rare variants via
      Sanger sequencing in HDC and SLITRK1, all of which are predicted to be
      deleterious. Intriguingly, one of the identified variants is in linkage
      disequilibrium with a variant that is included among the top hits of a genome
      wide association study for response to citalopram treatment, an antidepressant
      drug with off-label use also in obsessive compulsive disorder. Our findings
      provide additional evidence for the implication of these two genes in TS
      susceptibility and the possible role of these proteins in the pathobiology of TS
      should be revisited.

PMID- 27708562
TI  - Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay
      Formation Is Essential for Functional Regeneration.
AB  - Presently there exists no cure for spinal cord injury (SCI). However,
      transplantation of embryonic tissue into spinal cord (SC) lesions resulted in
      axon outgrowth across the lesion site and some functional recovery, fostering
      hope for future stem cell therapies. Although in vivo evidence for functional
      recovery is given, the exact cellular mechanism of the graft support remains
      elusive: either the grafted cells provide a permissive environment for the host
      tissue to regenerate itself or the grafts actually integrate functionally into
      the host neuronal network reconnecting the separated SC circuits. We tested the
      two hypotheses in an in vitro SC lesion model that is based on propagation of
      activity between two rat organotypic SC slices in culture. Transplantation of
      dissociated cells from E14 rat SC or forebrain (FB) re-established the relay of
      activity over the lesion site and thus, provoked functional regeneration.
      Combining patch-clamp recordings from transplanted cells with network activity
      measurements from the host tissue on multi-electrode arrays (MEAs) we here show
      that neurons differentiate from the grafted cells and integrate into the host
      circuits. Optogenetic silencing of neurons developed from transplanted embryonic
      mouse FB cells provides clear evidence that they replace the lost neuronal
      connections to relay and synchronize activity between the separated SC circuits.
      In contrast, transplantation of neurospheres (NS) induced neither the
      differentiation of mature neurons from the grafts nor an improvement of
      functional regeneration. Together these findings suggest, that the formation of
      neuronal relays from grafted embryonic cells is essential to re-connect
      segregated SC circuits.

PMID- 27708561
TI  - Protective Microglia and Their Regulation in Parkinson's Disease.
AB  - Microglia-mediated neuroinflammation is a hallmark of Parkinson's disease (PD).
      In the brains of patients with PD, microglia have both neurotoxic and
      neuroprotective effects, depending on their activation state. In this review, we
      focus on recent research demonstrating the neuroprotective role of microglia in
      PD. Accumulating evidence indicates that the protective mechanisms of microglia
      may result from their regulation of transrepression pathways via nuclear
      receptors, anti-inflammatory responses, neuron-microglia crosstalk, histone
      modification, and microRNA regulation. All of these mechanisms work together to
      suppress the production of neurotoxic inflammatory components. However, during
      the progression of PD, the detrimental effects of inflammation overpower the
      protective actions of microglia. Therefore, an in-depth exploration of the
      mechanisms underlying microglial neuroprotection, and a means of promoting the
      transformation of microglia to the protective phenotype, are urgently needed for
      the treatment of PD.

PMID- 27708564
TI  - Commentary: Perception and Reality: Why a Wholly Empirical Paradigm is Needed to
      Understand Vision.

PMID- 27708563
TI  - Basal Dendrites of Layer-III Pyramidal Neurons do not Scale with Changes in
      Cortical Magnification Factor in Macaque Primary Visual Cortex.
AB  - Neurons in the mammalian primary visual cortex (V1) are systematically arranged
      across the cortical surface according to the location of their receptive fields
      (RFs), forming a visuotopic (or retinotopic) map. Within this map, the foveal
      visual field is represented by a large cortical surface area, with increasingly
      peripheral visual fields gradually occupying smaller cortical areas. Although
      cellular organization in the retina, such as the spatial distribution of ganglion
      cells, can partially account for the eccentricity-dependent differences in the
      size of cortical representation, whether morphological differences exist across
      V1 neurons representing different eccentricities is unclear. In particular,
      morphological differences in dendritic field diameter might contribute to the
      magnified representation of the central visual field. Here, we addressed this
      question by measuring the basal dendritic arbors of pyramidal neurons of layer
      IIIC and adjoining layer III sublayers (in the Hassler's nomenclature) in macaque
      V1. We labeled layer-III pyramidal neurons at various retinotopic positions in V1
      by injecting lightly fixed brain tissue with intracellular dye, and then compared
      dendritic morphology across regions in the retinotopic map representing 0-20
      degrees  of eccentricity. The dendritic field area, total dendritic length,
      number of principal dendrites, branching complexity, spine density and total
      number of spines were all consistent across different retinotopic regions of V1.
      These results indicate that dendrites in layer-III pyramidal neurons are
      relatively homogeneous according to these morphometric parameters irrespective of
      their locations in this portion of the retinotopic map. The homogeneity of
      dendritic morphology in these neurons suggests that the emphasis of central
      visual field representation is not attributable to changes in the basal dendritic
      arbors of pyramidal neurons in layer III, but is likely the result of successive
      processes earlier in the retino-geniculo-striate pathway.

PMID- 27708565
TI  - Non-parametric Algorithm to Isolate Chunks in Response Sequences.
AB  - Chunking consists in grouping items of a sequence into small clusters, named
      chunks, with the assumed goal of lessening working memory load. Despite extensive
      research, the current methods used to detect chunks, and to identify different
      chunking strategies, remain discordant and difficult to implement. Here, we
      propose a simple and reliable method to identify chunks in a sequence and to
      determine their stability across blocks. This algorithm is based on a ranking
      method and its major novelty is that it provides concomitantly both the features
      of individual chunk in a given sequence, and an overall index that quantifies the
      chunking pattern consistency across sequences. The analysis of simulated data
      confirmed the validity of our method in different conditions of noise, chunk
      lengths and chunk numbers; moreover, we found that this algorithm was
      particularly efficient in the noise range observed in real data, provided that at
      least 4 sequence repetitions were included in each experimental block.
      Furthermore, we applied this algorithm to actual reaction time series gathered
      from 3 published experiments and were able to confirm the findings obtained in
      the original reports. In conclusion, this novel algorithm is easy to implement,
      is robust to outliers and provides concurrent and reliable estimation of chunk
      position and chunking dynamics, making it useful to study both sequence-specific
      and general chunking effects. The algorithm is available at:
      https://github.com/artipago/Non-parametric-algorithm-to-isolate-chunks-in
      response-sequences.

PMID- 27708566
TI  - Is the Sensorimotor Cortex Relevant for Speech Perception and Understanding? An
      Integrative Review.
AB  - In the neuroscience of language, phonemes are frequently described as multimodal
      units whose neuronal representations are distributed across perisylvian cortical
      regions, including auditory and sensorimotor areas. A different position views
      phonemes primarily as acoustic entities with posterior temporal localization,
      which are functionally independent from frontoparietal articulatory programs. To
      address this current controversy, we here discuss experimental results from
      functional magnetic resonance imaging (fMRI) as well as transcranial magnetic
      stimulation (TMS) studies. On first glance, a mixed picture emerges, with earlier
      research documenting neurofunctional distinctions between phonemes in both
      temporal and frontoparietal sensorimotor systems, but some recent work seemingly
      failing to replicate the latter. Detailed analysis of methodological differences
      between studies reveals that the way experiments are set up explains whether
      sensorimotor cortex maps phonological information during speech perception or
      not. In particular, acoustic noise during the experiment and 'motor noise' caused
      by button press tasks work against the frontoparietal manifestation of phonemes.
      We highlight recent studies using sparse imaging and passive speech perception
      tasks along with multivariate pattern analysis (MVPA) and especially
      representational similarity analysis (RSA), which succeeded in separating
      acoustic-phonological from general-acoustic processes and in mapping specific
      phonological information on temporal and frontoparietal regions. The question
      about a causal role of sensorimotor cortex on speech perception and understanding
      is addressed by reviewing recent TMS studies. We conclude that frontoparietal
      cortices, including ventral motor and somatosensory areas, reflect phonological
      information during speech perception and exert a causal influence on language
      understanding.

PMID- 27708568
TI  - Improving Production of Treated and Untreated Verbs in Aphasia: A Meta-Analysis.
AB  - Background: Demographic and clinical predictors of aphasia recovery have been
      identified in the literature. However, little attention has been devoted to
      identifying and distinguishing predictors of improvement for different outcomes,
      e.g., production of treated vs. untreated materials. These outcomes may rely on
      different mechanisms, and therefore be predicted by different variables.
      Furthermore, treatment features are not typically accounted for when studying
      predictors of aphasia recovery. This is partly due to the small numbers of cases
      reported in studies, but also to limitations of data analysis techniques usually
      employed. Method: We reviewed the literature on predictors of aphasia recovery,
      and conducted a meta-analysis of single-case studies designed to assess the
      efficacy of treatments for verb production. The contribution of demographic,
      clinical, and treatment-related variables was assessed by means of Random Forests
      (a machine-learning technique used in classification and regression). Two
      outcomes were investigated: production of treated (for 142 patients) and
      untreated verbs (for 166 patients). Results: Improved production of treated verbs
      was predicted by a three-way interaction of pre-treatment scores on tests for
      verb comprehension and word repetition, and the frequency of treatment sessions.
      Improvement in production of untreated verbs was predicted by an interaction
      including the use of morphological cues, presence of grammatical impairment, pre
      treatment scores on a test for noun comprehension, and frequency of treatment
      sessions. Conclusion: Improvement in the production of treated verbs occurs
      frequently. It may depend on restoring access to and/or knowledge of lexeme
      representations, and requires relative sparing of semantic knowledge (as measured
      by verb comprehension) and phonological output abilities (including working
      memory, as measured by word repetition). Improvement in the production of
      untreated verbs has not been reported very often. It may depend on the nature of
      impaired language representations, and the type of knowledge engaged by
      treatment: it is more likely to occur where abstract features (semantic and/or
      grammatical) are damaged and treated.

PMID- 27708567
TI  - Increased Sleep Depth in Developing Neural Networks: New Insights from Sleep
      Restriction in Children.
AB  - Brain networks respond to sleep deprivation or restriction with increased sleep
      depth, which is quantified as slow-wave activity (SWA) in the sleep
      electroencephalogram (EEG). When adults are sleep deprived, this homeostatic
      response is most pronounced over prefrontal brain regions. However, it is unknown
      how children's developing brain networks respond to acute sleep restriction, and
      whether this response is linked to myelination, an ongoing process in childhood
      that is critical for brain development and cortical integration. We implemented a
      bedtime delay protocol in 5- to 12-year-old children to obtain partial sleep
      restriction (1-night; 50% of their habitual sleep). High-density sleep EEG was
      assessed during habitual and restricted sleep and brain myelin content was
      obtained using mcDESPOT magnetic resonance imaging. The effect of sleep
      restriction was analyzed using statistical non-parametric mapping with supra
      threshold cluster analysis. We observed a localized homeostatic SWA response
      following sleep restriction in a specific parieto-occipital region. The
      restricted/habitual SWA ratio was negatively associated with myelin water
      fraction in the optic radiation, a developing fiber bundle. This relationship
      occurred bilaterally over parieto-temporal areas and was adjacent to, but did not
      overlap with the parieto-occipital region showing the most pronounced homeostatic
      SWA response. These results provide evidence for increased sleep need in
      posterior neural networks in children. Sleep need in parieto-temporal areas is
      related to myelin content, yet it remains speculative whether age-related myelin
      growth drives the fading of the posterior homeostatic SWA response during the
      transition to adulthood. Whether chronic insufficient sleep in the sensitive
      period of early life alters the anatomical generators of deep sleep slow-waves is
      an important unanswered question.

PMID- 27708569
TI  - Modeling and Theories of Pathophysiology and Physiology of the Basal Ganglia
      Thalamic-Cortical System: Critical Analysis.
AB  - Theories impact the movement disorders clinic, not only affecting the development
      of new therapies but determining how current therapies are used. Models are
      theories that are procedural rather than declarative. Theories and models are
      important because, as argued by Kant, one cannot know the thing-in-itself (das
      Ding an sich) and only a model is knowable. Further, biological variability
      forces higher level abstraction relevant for all variants. It is that abstraction
      that is raison d'etre of theories and models. Theories "connect the dots" to move
      from correlation to causation. The necessity of theory makes theories helpful or
      counterproductive. Theories and models of the pathophysiology and physiology of
      the basal ganglia-thalamic-cortical system do not spontaneously arise but have a
      history and consequently are legacies. Over the last 40 years, numerous theories
      and models of the basal ganglia have been proposed only to be forgotten or
      dismissed, rarely critiqued. It is not harsh to say that current popular theories
      positing increased neuronal activities in the Globus Pallidus Interna (GPi),
      excessive beta oscillations and increased synchronization not only fail to
      provide an adequate explication but are inconsistent with many observations. It
      is likely that their shared intellectual and epistemic inheritance plays a factor
      in their shared failures. These issues are critically examined. How one is to
      derive theories and models and have hope these will be better is explored as
      well.

PMID- 27708570
TI  - Effects of Age on Long Term Memory for Degraded Speech.
AB  - Prior research suggests that acoustical degradation impacts encoding of items
      into memory, especially in elderly subjects. We here aimed to investigate whether
      acoustically degraded items that are initially encoded into memory are more prone
      to forgetting as a function of age. Young and old participants were tested with a
      vocoded and unvocoded serial list learning task involving immediate and delayed
      free recall. We found that degraded auditory input increased forgetting of
      previously encoded items, especially in older participants. We further found that
      working memory capacity predicted forgetting of degraded information in young
      participants. In old participants, verbal IQ was the most important predictor for
      forgetting acoustically degraded information. Our data provide evidence that
      acoustically degraded information, even if encoded, is especially vulnerable to
      forgetting in old age.

PMID- 27708571
TI  - Error-Related Negativity and the Misattribution of State-Anxiety Following
      Errors: On the Reproducibility of Inzlicht and Al-Khindi ().
AB  - In their innovative study, Inzlicht and Al-Khindi (2012) demonstrated that
      participants who were allowed to misattribute their arousal and negative affect
      induced by errors to a placebo beverage had a reduced error-related negativity
      (ERN/Ne) compared to controls not being allowed to misattribute their arousal
      following errors. These results contribute to the ongoing debate that affect and
      motivation are interwoven with the cognitive processing of errors. Evidence that
      the misattribution of negative affect modulates the ERN/Ne is essential for
      understanding the mechanisms behind ERN/Ne. Therefore, and because of the growing
      debate on reproducibility of empirical findings, we aimed at replicating the
      misattribution effects on the ERN/Ne in a go/nogo task. Students were randomly
      assigned to a misattribution group (n = 48) or a control group (n = 51).
      Participants of the misattribution group consumed a beverage said to have side
      effects that would increase their physiological arousal, so that they could
      misattribute the negative affect induced by errors to the beverage. Participants
      of the control group correctly believed that the beverage had no side effects. As
      Inzlicht and Al-Khindi (2012), we did not observe performance differences between
      both groups. However, ERN/Ne differences between misattribution and control group
      could not be replicated, although the statistical power of the replication study
      was high. Evidence regarding the replication of performance and the non
      replication of ERN/Ne findings was confirmed by Bayesian statistics.

PMID- 27708572
TI  - Drifting States and Synchronization Induced Chaos in Autonomous Networks of
      Excitable Neurons.
AB  - The study of balanced networks of excitatory and inhibitory neurons has led to
      several open questions. On the one hand it is yet unclear whether the
      asynchronous state observed in the brain is autonomously generated, or if it
      results from the interplay between external drivings and internal dynamics. It is
      also not known, which kind of network variabilities will lead to irregular
      spiking and which to synchronous firing states. Here we show how isolated
      networks of purely excitatory neurons generically show asynchronous firing
      whenever a minimal level of structural variability is present together with a
      refractory period. Our autonomous networks are composed of excitable units, in
      the form of leaky integrators spiking only in response to driving currents,
      remaining otherwise quiet. For a non-uniform network, composed exclusively of
      excitatory neurons, we find a rich repertoire of self-induced dynamical states.
      We show in particular that asynchronous drifting states may be stabilized in
      purely excitatory networks whenever a refractory period is present. Other states
      found are either fully synchronized or mixed, containing both drifting and
      synchronized components. The individual neurons considered are excitable and
      hence do not dispose of intrinsic natural firing frequencies. An effective
      network-wide distribution of natural frequencies is however generated
      autonomously through self-consistent feedback loops. The asynchronous drifting
      state is, additionally, amenable to an analytic solution. We find two types of
      asynchronous activity, with the individual neurons spiking regularly in the pure
      drifting state, albeit with a continuous distribution of firing frequencies. The
      activity of the drifting component, however, becomes irregular in the mixed
      state, due to the periodic driving of the synchronized component. We propose a
      new tool for the study of chaos in spiking neural networks, which consists of an
      analysis of the time series of pairs of consecutive interspike intervals. In this
      space, we show that a strange attractor with a fractal dimension of about 1.8 is
      formed in the mentioned mixed state.

PMID- 27708573
TI  - Automated Neuroanatomical Relation Extraction: A Linguistically Motivated
      Approach with a PVT Connectivity Graph Case Study.
AB  - Identifying the relations among different regions of the brain is vital for a
      better understanding of how the brain functions. While a large number of studies
      have investigated the neuroanatomical and neurochemical connections among brain
      structures, their specific findings are found in publications scattered over a
      large number of years and different types of publications. Text mining techniques
      have provided the means to extract specific types of information from a large
      number of publications with the aim of presenting a larger, if not necessarily an
      exhaustive picture. By using natural language processing techniques, the present
      paper aims to identify connectivity relations among brain regions in general and
      relations relevant to the paraventricular nucleus of the thalamus (PVT) in
      particular. We introduce a linguistically motivated approach based on patterns
      defined over the constituency and dependency parse trees of sentences. Besides
      the presence of a relation between a pair of brain regions, the proposed method
      also identifies the directionality of the relation, which enables the creation
      and analysis of a directional brain region connectivity graph. The approach is
      evaluated over the manually annotated data sets of the WhiteText Project. In
      addition, as a case study, the method is applied to extract and analyze the
      connectivity graph of PVT, which is an important brain region that is considered
      to influence many functions ranging from arousal, motivation, and drug-seeking
      behavior to attention. The results of the PVT connectivity graph show that PVT
      may be a new target of research in mood assessment.

PMID- 27708574
TI  - Corrigendum: Data Citation in Neuroimaging: Proposed Best Practices for Data
      Identification and Attribution.
AB  - [This corrects the article on p. 34 in vol. 10, PMID: 27570508.].

PMID- 27708575
TI  - Physical Exercise Preserves Adult Visual Plasticity in Mice and Restores it after
      a Stroke in the Somatosensory Cortex.
AB  - The primary visual cortex (V1) is widely used to study brain plasticity, which is
      not only crucial for normal brain function, such as learning and memory, but also
      for recovery after brain injuries such as stroke. In standard cage (SC) raised
      mice, experience-dependent ocular dominance (OD) plasticity in V1 declines with
      age and is compromised by a lesion in adjacent and distant cortical regions. In
      contrast, mice raised in an enriched environment (EE), exhibit lifelong OD
      plasticity and are protected from losing OD plasticity after a stroke-lesion in
      the somatosensory cortex. Since SC mice with an access to a running wheel (RW)
      displayed preserved OD plasticity during aging, we investigated whether physical
      exercise might also provide a plasticity promoting effect after a cortical
      stroke. To this end, we tested if adult RW-raised mice preserved OD plasticity
      after stroke and also if short-term running after stroke restored OD plasticity
      to SC mice. Indeed, unlike mice without a RW, adult RW mice continued to show OD
      plasticity even after stroke, and a 2 weeks RW experience after stroke already
      restored lost OD plasticity. Additionally, the experience-enabled increase of the
      spatial frequency and contrast threshold of the optomotor reflex of the open eye,
      normally lost after a stroke, was restored in both groups of RW mice. Our data
      suggest that physical exercise alone can not only preserve visual plasticity into
      old age, but also restore it after a cortical stroke.

PMID- 27708576
TI  - A Novel CCM2 Gene Mutation Associated with Familial Cerebral Cavernous
      Malformation.
AB  - Background: Cerebral cavernous malformations (CCMs) are common vascular
      malformations that predominantly arise in the central nervous system and are
      mainly characterized by enlarged vascular cavities without intervening brain
      parenchyma. Familial CCMs (FCCMs) is inherited in an autosomal dominant pattern
      with incomplete penetrance and variable symptoms. Methods: Mutations of three
      pathogenic genes, CCM1, CCM2, and CCM3, were investigated by direct DNA
      sequencing in a Chinese family with multiple CCM lesions. Results: Four
      heterozygous variants in the CCM2 gene, including one deletion (c.95delC), a
      missense mutation (c.358G>A, p.V120I), one silent mutation (c.915G>A, p.T305T),
      and a substitution (c. *1452 T>C), were identified in the subjects with multiple
      CCM lesions, but not in a healthy sibling. Among these variants, the c.95delC
      deletion is a novel mutation which is expected to cause a premature termination
      codon. It is predicted to produce a truncated CCM2 protein lacking the PTB and C
      terminal domains, thus disrupting the molecular functions of CCM2. Conclusions:
      The novel truncating mutation in the CCM2 gene, c.95delC, may be responsible for
      multiple CCM lesions in a part of FCCM. In addition, it may represent a potential
      genetic biomarker for early diagnosis of FCCM.

PMID- 27708577
TI  - Neuroanatomical Alterations in Tinnitus Assessed with Magnetic Resonance Imaging.
AB  - Previous studies of anatomical changes associated with tinnitus have provided
      inconsistent results, with some showing significant cortical and subcortical
      changes, while others have found effects due to hearing loss, but not tinnitus.
      In this study, we examined changes in brain anatomy associated with tinnitus
      using anatomical scans from 128 participants with tinnitus and hearing loss,
      tinnitus with clinically normal hearing, and non-tinnitus controls with
      clinically normal hearing. The groups were matched for hearing loss, age and
      gender. We employed voxel- and surface-based morphometry (SBM) to investigate
      gray and white matter volume and thickness within regions-of-interest (ROI) that
      were based on the results of previous studies. The largest overall effects were
      found for age, gender, and hearing loss. With regard to tinnitus, analysis of ROI
      revealed numerous small increases and decreases in gray matter and thickness
      between tinnitus and non-tinnitus controls, in both cortical and subcortical
      structures. For whole brain analysis, the main tinnitus-related significant
      clusters were found outside sensory auditory structures. These include a decrease
      in cortical thickness for the tinnitus group compared to controls in the left
      superior frontal gyrus (SFG), and a decrease in cortical volume with hearing loss
      in left Heschl's gyrus (HG). For masked analysis, we found a decrease in gray
      matter volume in the right Heschle's gyrus for the tinnitus group compared to the
      controls. We found no changes in the subcallosal region as reported in some
      previous studies. Overall, while some of the morphological differences observed
      in this study are similar to previously published findings, others are entirely
      different or even contradict previous results. We highlight other discrepancies
      among previous results and the increasing need for a more precise subtyping of
      the condition.

PMID- 27708578
TI  - Adherence and Patients' Experiences with the Use of Capecitabine in Daily
      Practice.
AB  - Introduction: Capecitabine is a widely prescribed oral anticancer agent. We
      studied medication adherence and explored its use in daily practice from a
      patients' perspective. Patients and Methods: Patients (n = 92) starting
      capecitabine were followed up to five 3-week cycles. Adherence was assessed using
      a pill count, pharmacy data and dosing information from the patients' medical
      file. Self-reported adherence was measured using the Medication Adherence Report
      Scale (MARS). At baseline and during week 2 of cycles 1, 3, and 5, patients
      filled out questionnaires about quality of life, symptoms, attitude toward
      medicines and disease and use in daily practice. Simultaneously, blood samples
      were taken to determine the area under the curve (AUC) of 5'-deoxy-5
      fluorouridine (5'-DFUR), 5-fluorouracil (5-FU), and alpha-fluoro-beta-alanine
      (FBAL) by a population pharmacokinetic model. Associations between AUCs and
      patient-reported symptoms were tested for cycles 3 and 5. Results: Most patients
      (84/92; 91%) had an adherence rate of >=95 and <= 105%. The percentage of
      patients reporting any non-adherence behavior measured with MARS increased from
      16% at cycle 1 to 29% at cycle 5. Symptoms were reported frequently and the
      dosing regimen was adjusted by the physician at least once in 62% of patients. In
      multivariate analysis the probability of an adjustment increased with the number
      of co-medication (OR 1.19, 95% CI: 1.03-1.39) and a stronger emotional response
      to the disease (OR 1.32, 95% CI: 1.10-1.59). The AUC of 5'-DFUR was associated
      with weight loss (OR 1.10, 95% CI: 1.01-1.19), AUC of FBAL with hand-foot
      syndrome (OR 0.90, 95% CI: 0.83-0.99), rhinorrhea (OR 1.21, 95% CI: 1.03-1.42
      weight loss (OR 1.09, 95% CI: 1.00-1.20) and depression (OR 0.90, 95% CI: 0.82
      0.99). Side effects were reported by one third of patients as the reason to
      discontinue treatment. Conclusion: Adherence to capecitabine was generally high.
      Nevertheless, adherence measured with MARS decreased over time Adherence
      management to support implementation of correct capecitabine use is specifically
      relevant in longer term treatment. In addition, it appears that adverse event
      management is important to support persistence. With the extending armamentarium
      of oral targeted anticancer agents and prolonged treatment duration, we expect
      the issue of medication adherence of increasing importance in oncology.

PMID- 27708580
TI  - Innovative Strategies to Develop Chemical Categories Using a Combination of
      Structural and Toxicological Properties.
AB  - Interest is increasing in the development of non-animal methods for toxicological
      evaluations. These methods are however, particularly challenging for complex
      toxicological endpoints such as repeated dose toxicity. European Legislation,
      e.g., the European Union's Cosmetic Directive and REACH, demands the use of
      alternative methods. Frameworks, such as the Read-across Assessment Framework or
      the Adverse Outcome Pathway Knowledge Base, support the development of these
      methods. The aim of the project presented in this publication was to develop
      substance categories for a read-across with complex endpoints of toxicity based
      on existing databases. The basic conceptual approach was to combine structural
      similarity with shared mechanisms of action. Substances with similar chemical
      structure and toxicological profile form candidate categories suitable for read
      across. We combined two databases on repeated dose toxicity, RepDose database,
      and ELINCS database to form a common database for the identification of
      categories. The resulting database contained physicochemical, structural, and
      toxicological data, which were refined and curated for cluster analyses. We
      applied the Predictive Clustering Tree (PCT) approach for clustering chemicals
      based on structural and on toxicological information to detect groups of
      chemicals with similar toxic profiles and pathways/mechanisms of toxicity. As
      many of the experimental toxicity values were not available, this data was
      imputed by predicting them with a multi-label classification method, prior to
      clustering. The clustering results were evaluated by assessing chemical and
      toxicological similarities with the aim of identifying clusters with a
      concordance between structural information and toxicity profiles/mechanisms. From
      these chosen clusters, seven were selected for a quantitative read-across, based
      on a small ratio of NOAEL of the members with the highest and the lowest NOAEL in
      the cluster (< 5). We discuss the limitations of the approach. Based on this
      analysis we propose improvements for a follow-up approach, such as incorporation
      of metabolic information and more detailed mechanistic information. The software
      enables the user to allocate a substance in a cluster and to use this information
      for a possible read- across. The clustering tool is provided as a free web
      service, accessible at http://mlc-reach.informatik.uni-mainz.de.

PMID- 27708579
TI  - Pharmacogenomics of Prostaglandin and Leukotriene Receptors.
AB  - Individual genetic background together with environmental effects are thought to
      be behind many human complex diseases. A number of genetic variants, mainly
      single nucleotide polymorphisms (SNPs), have been shown to be associated with
      various pathological and inflammatory conditions, representing potential
      therapeutic targets. Prostaglandins (PTGs) and leukotrienes (LTs) are eicosanoids
      derived from arachidonic acid and related polyunsaturated fatty acids that
      participate in both normal homeostasis and inflammatory conditions. These
      bioactive lipid mediators are synthesized through two major multistep enzymatic
      pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main
      physiological effects of PTGs include vasodilation and vascular leakage (PTGE2);
      mast cell maturation, eosinophil recruitment, and allergic responses (PTGD2);
      vascular and respiratory smooth muscle contraction (PTGF2), and inhibition of
      platelet aggregation (PTGI2). LTB4 is mainly involved in neutrophil recruitment,
      vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs)
      (LTC4, LTD4, and LTE4) induce bronchoconstriction and neutrophil extravasation,
      and also participate in vascular leakage. PTGs and LTs exert their biological
      functions by binding to cognate receptors, which belong to the seven
      transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding
      these receptors may influence their functionality and have a role in disease
      susceptibility and drug treatment response. In this review we summarize SNPs in
      PTGs and LTs receptors and their relevance in human diseases. We also provide
      information on gene expression. Finally, we speculate on future directions for
      this topic.

PMID- 27708581
TI  - Activation of Endothelial Pro-resolving Anti-Inflammatory Pathways by Circulating
      Microvesicles from Non-muscular Myosin Light Chain Kinase-Deficient Mice.
AB  - Microvesicles, small membrane vesicles released from cells, have beneficial
      and/or deleterious effects in sepsis. We previously reported that non-muscle
      myosin light chain kinase (nmMLCK) deletion protects mice against endotoxic shock
      by reducing inflammation. Here, we have evaluated the consequences of nmMLCK
      deletion on microvesicle phenotypes and their effects on mouse aortic endothelial
      cells in association with vascular inflammation and endothelial dysfunction
      during endotoxic shock induced by lipopolysaccharide in mice. Treatment with
      lipopolysaccharide induced an increase in levels of circulating microvesicles in
      wild type but not in nmMLCK-deficient mice. Microvesicles from nmMLCK-deficient
      mice (MVsnmMLCK-/-) prevented the inflammatory effects of lipopolysaccharide with
      concomitant increase of anti- inflammatory and reduction of pro-inflammatory
      secretome in mouse aortic endothelial cells. In addition, MVsnmMLCK-/- reduced
      the efficacy of lipopolysaccharide to increase aortic oxidative and nitrosative
      stresses as well as macrophage infiltration in the aorta. Moreover, MVsnmMLCK-/-
      prevented ex vivo endothelial dysfunction, vascular hyporeactivity, and in vivo
      overproduction of nitric oxide in heart and liver in response to
      lipopolysaccharide. Altogether, these findings provide evidence that nmMLCK
      deletion generates circulating microvesicles displaying protective effects by
      activating endothelial pro-resolving anti-inflammatory pathways allowing the
      effective down-regulation of oxidative and nitrative stresses associated with
      endotoxic shock. Thus, nmMLCK plays a pivotal role in susceptibility to sepsis
      via the control of cellular activation and release of circulating microvesicles.

PMID- 27708582
TI  - High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the
      Prevention and Treatment of Lung Disease.
AB  - Apolipoprotein A-I (apoA-I) and high-density lipoproteins (HDL) mediate reverse
      cholesterol transport out of cells. Furthermore, HDL has additional protective
      functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and
      vasoprotective effects. In contrast, HDL can become dysfunctional with a
      reduction in both cholesterol efflux and anti-inflammatory properties in the
      setting of disease or the acute phase response. These paradigms are increasingly
      being recognized to be active in the pulmonary system, where apoA-I and HDL have
      protective effects in normal lung health, as well as in a variety of disease
      states, including acute lung injury (ALI), asthma, chronic obstructive pulmonary
      disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and
      viral pneumonia. Similar to observations in cardiovascular disease, however, HDL
      may become dysfunctional and contribute to disease pathogenesis in respiratory
      disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have
      protective effects in animal models of ALI, asthma, pulmonary hypertension, and
      influenza pneumonia. These findings provide evidence to support the concept that
      apoA-I mimetic peptides might be developed into a new treatment that can either
      prevent or attenuate the manifestations of lung diseases, such as asthma. Thus,
      the lung is positioned to take a page from the cardiovascular disease playbook
      and utilize the protective properties of HDL and apoA-I as a novel therapeutic
      approach.

PMID- 27708583
TI  - Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid
      Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea.
AB  - The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN)
      formulations for oral delivery of loperamide (LPM) to treat different types of
      diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic
      properties in vivo. In this work, glyceryl trimyristate (Dynasan 114)
      nanoparticles containing the drug LPM and sodium cholate as a stabilizer were
      prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs,
      namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug) and LPM-SLN-2
      (LPM-SLN with a low ratio rate of lipid to drug), were prepared by the solvent
      evaporation method. A change in the lipid concentration affects the
      characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 +/- 18 nm
      and 519 +/- 36 nm, separately, as analyzed by dynamic light scattering. The LPM
      SLNs were found to be round with a smooth surface, as observed using a
      transmission electron microscope and a scanning electron microscope. The average
      encapsulation efficiencies were 87 +/- 3.78% w/w and 84 +/- 5.17%, accordingly.
      In the in vitro release experiments, LPM-SLNs showed a continuous release profile
      of LPM without any burst release. The oral bioavailability of LPM-SLNs was
      analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227
      and 153%, respectively, as compared that of the LPM tablet. There was no
      difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM
      SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2
      having the same swift action as the LPM tablet. These results demonstrate the
      potential of LPM-SLNs in the oral delivery of LPM to treat different types of
      diarrhea.

PMID- 27708584
TI  - Multiscale Mathematical Modeling in Dental Tissue Engineering: Toward Computer
      Aided Design of a Regenerative System Based on Hydroxyapatite Granules, Focussing
      on Early and Mid-Term Stiffness Recovery.
AB  - We here explore for the very first time how an advanced multiscale mathematical
      modeling approach may support the design of a provenly successful tissue
      engineering concept for mandibular bone. The latter employs double-porous,
      potentially cracked, single millimeter-sized granules packed into an overall
      conglomerate-type scaffold material, which is then gradually penetrated and
      partially replaced by newly grown bone tissue. During this process, the newly
      developing scaffold-bone compound needs to attain the stiffness of mandibular
      bone under normal physiological conditions. In this context, the question arises
      how the compound stiffness is driven by the key design parameters of the tissue
      engineering system: macroporosity, crack density, as well as scaffold
      resorption/bone formation rates. We here tackle this question by combining the
      latest state-of-the-art mathematical modeling techniques in the field of
      multiscale micromechanics, into an unprecedented suite of highly efficient, semi
      analytically defined computation steps resolving several levels of hierarchical
      organization, from the millimeter- down to the nanometer-scale. This includes
      several types of homogenization schemes, namely such for porous polycrystals with
      elongated solid elements, for cracked matrix-inclusion composites, as well as for
      assemblies of coated spherical compounds. Together with the experimentally known
      stiffnesses of hydroxyapatite crystals and mandibular bone tissue, the new
      mathematical model suggests that early stiffness recovery (i.e., within several
      weeks) requires total avoidance of microcracks in the hydroxyapatite scaffolds,
      while mid-term stiffness recovery (i.e., within several months) is additionally
      promoted by provision of small granule sizes, in combination with high bone
      formation and low scaffold resorption rates.

PMID- 27708585
TI  - Comparative Analysis of the Equivital EQ02 Lifemonitor with Holter Ambulatory ECG
      Device for Continuous Measurement of ECG, Heart Rate, and Heart Rate Variability:
      A Validation Study for Precision and Accuracy.
AB  - Background: The Equivital (EQ02) is a multi-parameter telemetric device offering
      both real-time and/or retrospective, synchronized monitoring of ECG, HR, and HRV,
      respiration, activity, and temperature. Unlike the Holter, which is the gold
      standard for continuous ECG measurement, EQO2 continuously monitors ECG via
      electrodes interwoven in the textile of a wearable belt. Objective: To compare
      EQ02 with the Holter for continuous home measurement of ECG, heart rate (HR), and
      heart rate variability (HRV). Methods: Eighteen healthy participants wore,
      simultaneously for 24 h, the Holter and EQ02 monitors. Per participant, averaged
      HR, and HRV per 5 min from the two devices were compared using Pearson
      correlation, paired T-test, and Bland-Altman analyses. Accuracy and precision
      metrics included mean absolute relative difference (MARD). Results: Artifact
      content of EQ02 data varied widely between (range 1.93-56.45%) and within (range
      0.75-9.61%) participants. Comparing the EQ02 to the Holter, the Pearson
      correlations were respectively 0.724, 0.955, and 0.997 for datasets containing
      all data and data with < 50 or < 20% artifacts respectively. For datasets
      containing respectively all data, data with < 50, or < 20% artifacts, bias
      estimated by Bland-Altman analysis was -2.8, -1.0, and -0.8 beats per minute and
      24 h MARD was 7.08, 3.01, and 1.5. After selecting a 3-h stretch of data
      containing 1.15% artifacts, Pearson correlation was 0.786 for HRV measured as
      standard deviation of NN intervals (SDNN). Conclusions: Although the EQ02 can
      accurately measure ECG and HRV, its accuracy and precision is highly dependent on
      artifact content. This is a limitation for clinical use in individual patients.
      However, the advantages of the EQ02 (ability to simultaneously monitor several
      physiologic parameters) may outweigh its disadvantages (higher artifact load) for
      research purposes and/ or for home monitoring in larger groups of study
      participants. Further studies can be aimed at minimizing the artifacts.

PMID- 27708587
TI  - In situ, Reversible Gating of a Mechanosensitive Ion Channel through Protein
      Lipid Interactions.
AB  - Understanding the functioning of ion channels, as well as utilizing their
      properties for biochemical applications requires control over channel activity.
      Herein we report a reversible control over the functioning of a mechanosensitive
      ion channel by interfering with its interaction with the lipid bilayer. The
      mechanosensitive channel of large conductance from Escherichia coli is
      reconstituted into liposomes and activated to its different sub-open states by
      titrating lysophosphatidylcholine (LPC) into the lipid bilayer. Activated
      channels are closed back by the removal of LPC out of the membrane by bovine
      serum albumin (BSA). Electron paramagnetic resonance spectra showed the LPC-dose
      dependent gradual opening of the channel pore in the form of incrementally
      increasing spin label mobility and decreasing spin-spin interaction. A method to
      reversibly open and close mechanosensitive channels to distinct sub-open
      conformations during their journey from the closed to the fully open state
      enables detailed structural studies to follow the conformational changes during
      channel functioning. The ability of BSA to revert the action of LPC opens new
      perspectives for the functional studies of other membrane proteins that are known
      to be activated by LPC.

PMID- 27708586
TI  - Modeling Ca2+-Bound Troponin in Excitation Contraction Coupling.
AB  - To explain disparate decay rates of cytosolic Ca2+ and structural changes in the
      thin filaments during a twitch, we model the time course of Ca2+-bound troponin
      (Tn) resulting from the free Ca2+ transient of fast skeletal muscle. In fibers
      stretched beyond overlap, the decay of Ca2+ as measured by a change in fluo-3
      fluorescence is significantly slower than the intensity decay of the meridional
      1/38.5 nm-1 reflection of Tn; this is not simply explained by considering only
      the Ca2+ binding properties of Tn alone (Matsuo et al., 2010). We apply a
      comprehensive model that includes the known Ca2+ binding properties of Tn in the
      context of the thin filament with and without cycling crossbridges. Calculations
      based on the model predict that the transient of Ca2+-bound Tn correlates with
      either the fluo-3 time course in muscle with overlapping thin and thick filaments
      or the intensity of the meridional 1/38.5 nm-1 reflection in overstretched
      muscle. Hence, cycling crossbridges delay the dissociation of Ca2+ from Tn.
      Correlation with the fluo-3 fluorescence change is not causal given that the
      transient of Ca2+-bound Tn depends on sarcomere length, whereas the fluo-3
      fluorescence change does not. Transient positions of tropomyosin calculated from
      the time course of Ca2+-bound Tn are in reasonable agreement with the transient
      of measured perturbations of the Tn repeat in overlap and non-overlap muscle
      preparations.

PMID- 27708588
TI  - Application of Glycerol for Induced Powdery Mildew Resistance in Triticum
      aestivum L.
AB  - Previous work has demonstrated that glycerol-3-phosphate (G3P) and oleic acid
      (18:1) are two important signal molecules associated with plant resistance to
      fungi. In this article, we provide evidence that a 3% glycerol spray application
      1-2 days before powdery mildew infection and subsequent applications once every 4
      days was sufficient to stimulate the plant defense responses without causing any
      significant damage to wheat leaves. We found that G3P and oleic acid levels were
      markedly induced by powdery mildew infection. In addition, TaGLI1 (encoding a
      glycerol kinase) and TaSSI2 (encoding a stearoylacyl carrier protein fatty acid
      desaturase), two genes associated with the glycerol and fatty acid (FA) pathways,
      respectively, were induced by powdery mildew infection, and their promoter
      regions contain some fungal response elements. Moreover, exogenous application of
      glycerol increased the G3P level and decreased the level of oleic acid (18:1).
      Glycerol application induced the expression of pathogenesis-related (PR) genes
      (TaPR-1, TaPR-2, TaPR-3, TaPR-4, and TaPR-5), induced the generation of reactive
      oxygen species (ROS) before powdery mildew infection, and induced salicylic acid
      (SA) accumulation in wheat leaves. Further, we sprayed glycerol in a wheat field
      and found that it significantly (p < 0.05) reduced the severity of powdery mildew
      disease and lessened disease-associated kernel weight loss, all without causing
      any noticeable degradation in wheat seed quality.

PMID- 27708589
TI  - Synergistic Co-activation Increases the Extent of Mechanical Interaction between
      Rat Ankle Plantar-Flexors.
AB  - Force transmission between rat ankle plantar-flexors has been found for
      physiological muscle lengths and relative positions, but only with all muscles
      maximally activated. The aims of this study were to assess intermuscular
      mechanical interactions between ankle plantar-flexors during (i) fully passive
      conditions, (ii) excitation of soleus (SO), (iii) excitation of lateral
      gastrocnemius (LG), and (iv) during co-activation of SO, and LG (SO&LG). We
      assessed effects of proximal lengthening of LG and plantaris (PL) muscles (i.e.,
      simulating knee extension) on forces exerted at the distal SO tendon (FSO) and on
      the force difference between the proximal and distal LG+PL tendons (DeltaFLG+PL)
      of the rat. LG+PL lengthening increased FSO to a larger extent (p = 0.017) during
      LG excitation (0.0026 N/mm) than during fully passive conditions (0.0009 N/mm).
      Changes in FSO in response to LG+PL lengthening were lower (p = 0.002) during SO
      only excitation (0.0056 N/mm) than during SO&LG excitation (0.0101 N/mm). LG+PL
      lengthening changed DeltaFLG+PL to a larger extent (p = 0.007) during SO
      excitation (0.0211 N/mm) than during fully passive conditions (0.0157 N/mm). In
      contrast, changes in DeltaFLG+PL in response to LG+PL lengthening during LG
      excitation (0.0331 N/mm) were similar (p = 0.161) to that during SO&LG excitation
      (0.0370 N/mm). In all conditions, changes of FSO were lower than those of
      DeltaFLG+PL. This indicates that muscle forces were transmitted not only between
      LG+PL and SO, but also between LG+PL and other surrounding structures. In
      addition, epimuscular myofascial force transmission between rat ankle plantar
      flexors was enhanced by muscle activation. However, the magnitude of this
      interaction was limited.

PMID- 27708590
TI  - QT Interval Derived Measurements in Patients with Cardiac Syndrome X Compared to
      Coronary Artery Disease.
AB  - Previous studies assessing effect of ischemia on ventricular repolarization are
      mostly directed toward patients with coronary artery disease (CAD); however,
      similar reports on cardiac syndrome X (CSX) are scarce. Whether microvascular
      dysfunction of CSX and ischemia induced by CAD produce comparable effect on
      ventricular repolarization is unclear and deserve further studies. In the present
      study, ECG measures of ventricular repolarization were compared between CAD and
      CSX patients (40 subjects in each group). Following evaluation of
      sociodemographic characteristics, medical and past medical history, a resting ECG
      was used to assess measurements of ventricular repolarization in each patient,
      namely, QT interval (QT), corrected QT interval (QTc), QT dispersion (QTd),
      corrected QT dispersion (QTcd), adjacent QT dispersion (AdQTd), QT dispersion
      ratio (QTdR), JT dispersion (JTd), and Corrected JT dispersion (JTcd). Results
      showed comparable QT intervals and QTd in CAD and CSX patients even after
      adjustment for the possible variations in gender, age and body mass index of the
      studied groups. Although JTd was increased in CSX subjects (26.6 +/- 7.2 ms)
      compared with CAD patients (22.7 +/- 6.5 ms, p = 0.019), statistical significance
      disappeared after correcting JT for variations in heart rate. QT and QTc were
      significantly below 440 ms in CAD as well as CSX patients (p < 0.001). In
      contrast, maximum QTd, maximum QTcd and AdQTd of CAD and CSX patients were
      significantly above 440 ms (p < 0.001). The means of JTd and JTcd were
      significantly above 22 ms and 24 ms respectively (p < 0.001, p = 0.001) in CSX
      but not CAD patients (p = 0.529, p = 0.281). The present findings clearly
      demonstrate comparable measures of ventricular repolarization in CAD and CSX
      patients and consequently an equal risk of cardiac events in both groups.

PMID- 27708592
TI  - Fuzzy Nonnative Phonolexical Representations Lead to Fuzzy Form-to-Meaning
      Mappings.
AB  - The present paper explores nonnative (L2) phonological encoding of lexical
      entries and dissociates the difficulties associated with L2 phonological and
      phonolexical encoding by focusing on similarly sounding L2 words that are not
      differentiated by difficult phonological contrasts. We test two main claims of
      the fuzzy lexicon hypothesis: (1) L2 fuzzy phonolexical representations are not
      fully specified and lack details at both phonological and phonolexical levels of
      representation (Experiment 1); and (2) fuzzy phonolexical representations can
      lead to establishing incorrect form-to-meaning mappings (Experiment 2). The
      Russian-English Translation Judgment Task (Experiment 1, TJT) explores how the
      degree of phonolexical similarity between a word and its lexical competitor
      affects lexical access of Russian words. Words with smaller phonolexical distance
      (e.g., parent-parrot) show longer reaction times and lower accuracy compared to
      words with a larger phonolexical distance (e.g., parent-parchment) in lower
      proficiency nonnative speakers, and, to a lesser degree, higher-proficiency
      speakers. This points to a lack of detail in nonnative phonolexical
      representations necessary for efficient lexical access. The Russian Pseudo
      Semantic Priming task (Experiment 2, PSP) addresses the vulnerability of form-to
      meaning mappings as a consequence of fuzzy phonolexical representations in L2. We
      primed the target with a word semantically related to its phonological
      competitor, or a potentially confusable word. The findings of Experiment 2 extend
      the results of Experiment 1 that, unlike native speakers, nonnative speakers do
      not properly encode phonolexical information. As a result, they are prone to
      access an incorrect lexical representation of a competitor word, as indicated by
      a slowdown in the judgments to confusable words. The study provides evidence that
      fuzzy phonolexical representations result in unfaithful form-to-meaning mappings,
      which lead to retrieval of incorrect semantic content. The results of the study
      are in line with existing research in support of less detailed L2 phonolexical
      representations, and extend the findings to show that the fuzziness of
      phonolexical representations can arise even when confusable words are not
      differentiated by difficult phonological contrasts.

PMID- 27708593
TI  - Sexual Aggression Victimization and Perpetration among Male and Female College
      Students in Chile.
AB  - Evidence on the prevalence of sexual aggression among college students is
      primarily based on studies from Western countries. In Chile, a South American
      country strongly influenced by the Catholic Church, little research on sexual
      aggression among college students is available. Therefore, the purpose of the
      present study was to examine the prevalence of sexual aggression victimization
      and perpetration since the age of 14 (the legal age of consent) in a sample of
      male and female students aged between 18 and 29 years from five Chilean
      universities (N = 1135), to consider possible gender differences, and to study
      the extent to which alcohol was involved in the reported incidents of
      perpetration and victimization. Sexual aggression victimization and perpetration
      was measured with a Chilean Spanish version of the Sexual Aggression and
      Victimization Scale (SAV-S), which includes three coercive strategies (use or
      threat of physical force, exploitation of an incapacitated state, and verbal
      pressure), three victim-perpetrator constellations (current or former partners,
      friends/acquaintances, and strangers), and four sexual acts (sexual touch,
      attempted sexual intercourse, completed sexual intercourse, and other sexual
      acts, such as oral sex). Overall, 51.9% of women and 48.0% of men reported at
      least one incident of sexual victimization, and 26.8% of men and 16.5% of women
      reported at least one incident of sexual aggression perpetration since the age of
      14. For victimization, only few gender differences were found, but significantly
      more men than women reported sexual aggression perpetration. A large proportion
      of perpetrators also reported victimization experiences. Regarding victim
      perpetrator relationship, sexual aggression victimization and perpetration were
      more common between persons who knew each other than between strangers. Alcohol
      use by the perpetrator, victim, or both was involved in many incidents of sexual
      aggression victimization and perpetration, particularly among strangers. The
      present data are the first to provide a systematic and detailed picture of sexual
      aggression among college students in Chile, including victimization and
      perpetration reports by both men and women and confirming the critical role of
      alcohol established in past research from Western countries.

PMID- 27708594
TI  - Cross-Lagged Relationships between Morphological Awareness and Reading
      Comprehension among Chinese Children.
AB  - The present study examined the developmental relationship between morphological
      awareness (MA) and reading comprehension (RC) using a 2-year and four-wave cross
      lagged design with a sample of 149 Chinese children (80 males and 69 females). We
      measured children's MA, word reading (WR), and RC from T1 to T4, in addition to
      phonological awareness, vocabulary knowledge, and general cognitive ability at T1
      as control measures. Four plausible cross-lagged models were assessed and
      compared to examine the direction of the developmental relationships between MA
      and RC over time. Results found support for a reciprocal-causation model, that
      is, MA stably predicted subsequent RC, and the reverse relation was also found.
      Longitudinal mediation analyses revealed that WR partially mediated the
      relationship between MA and RC in Chinese children. These findings extend our
      understanding of the relationship between MA and RC. The practical implications
      for these two developing skills in Chinese children are discussed.

PMID- 27708595
TI  - Limited Near and Far Transfer Effects of Jungle Memory Working Memory Training on
      Learning Mathematics in Children with Attentional and Mathematical Difficulties.
AB  - The goal of this randomized controlled trial was to investigate whether Jungle
      Memory working memory training (JM) affects performance on working memory tasks,
      performance in mathematics and gains made on a mathematics training (MT) in
      school aged children between 9-12 years old (N = 64) with both difficulties in
      mathematics, as well as attention and working memory. Children were randomly
      assigned to three groups and were trained in two periods: (1) JM first, followed
      by MT, (2) MT first, followed by JM, and (3) a control group that received MT
      only. Bayesian analyses showed possible short term effects of JM on near transfer
      measures of verbal working memory, but none on visual working memory.
      Furthermore, support was found for the hypothesis that children that received JM
      first, performed better after MT than children who did not follow JM first or did
      not train with JM at all. However, these effects could be explained at least
      partly by frequency of training effects, possibly due to motivational issues, and
      training-specific factors. Furthermore, it remains unclear whether the effects
      found on improving mathematics were actually mediated by gains in working memory.
      It is argued that JM might not train the components of working memory involved in
      mathematics sufficiently. Another possible explanation can be found in the
      training's lack of adaptivity, therefore failing to provide the children with
      tailored instruction and feedback. Finally, it was hypothesized that, since
      effect sizes are generally small, training effects are bound to a critical period
      in development.

PMID- 27708596
TI  - The Transfer of Object Learning after Training with Multiple Exemplars.
AB  - Object recognition improves with training. This training effect only partially
      generalizes to untrained images of the trained objects (new exemplars,
      orientation,...). The aim of this study is to investigate whether and to what
      extent the learning transfer improves when participants are trained with more
      exemplars of an object. Participants were trained to recognize two sets of
      stimuli using a backward masking paradigm. During training with the first set,
      only one exemplar of each object was presented. The second set was trained using
      four exemplars of each object. After 3 days of training, participants were tested
      on all the trained exemplars and a completely new exemplar of the same objects.
      In addition, recognition performance was compared to a set of completely new
      objects. For the objects of which four exemplars were used during training,
      participants showed more generalization toward new exemplars compared to when
      they were only trained with one exemplar. Part of the generalization effect
      extended to completely new objects. In conclusion, more variation during training
      leads to more generalization toward new visual stimuli.

PMID- 27708597
TI  - Methodological Considerations about the Use of Bimodal Oddball P300 in
      Psychiatry: Topography and Reference Effect.
AB  - Event-related potentials (ERPs) bimodal oddball task has disclosed increased
      sensitivity to show P300 modulations to subclinical symptoms. Even if the utility
      of such a procedure has still to be confirmed at a clinical level, gathering
      normative values of this new oddball variant may be of the greatest interest. We
      specifically addressed the challenge of defining the best location for the
      recording of P3a and P3b components and selecting the best reference to use by
      investigating the effect of an offline re-reference procedure on recorded bimodal
      P3a and P3b. Forty young and healthy subjects were submitted to a bimodal
      (synchronized and always congruent visual and auditory stimuli) three-stimulus
      oddball task in which 140 frequent bimodal stimuli, 30 deviant "target" stimuli
      and 30 distractors were presented. Task consisted in clicking as soon as possible
      on the targets, and not paying attention to frequent stimuli and distractors.
      This procedure allowed us to record, for each individual, the P3a component,
      referring to the novelty process related to distractors processing, and the P3b
      component, linked to the processing of the target stimuli. Results showed that
      both P3a and P3b showed maximal amplitude in Pz. However, P3a displayed a more
      central distribution. Nose reference was also shown to give maximal amplitudes
      compared with average and linked mastoids references. These data were discussed
      in light of the necessity to develop multi-site recording guidelines to furnish
      sets of ERPs data comparable across laboratories.

PMID- 27708599
TI  - Editorial: The Grammar of Multilingualism.

PMID- 27708598
TI  - Crave, Like, Eat: Determinants of Food Intake in a Sample of Children and
      Adolescents with a Wide Range in Body Mass.
AB  - Obesity is a heterogeneous condition with obese individuals displaying different
      eating patterns. Growing evidence suggests that there is a subgroup of obese
      adults that is marked by frequent and intense food cravings and addiction-like
      consumption of high-calorie foods. Little is known, however, about such a
      subgroup of obese individuals in childhood and adolescence. In the present study,
      a sample of children and adolescents with a wide range in body mass was
      investigated and trait food craving, liking for and intake of high- and low
      calorie foods was measured. One-hundred and forty-two children and adolescents
      (51.4% female, n = 73; Mage = 13.7 years, SD = 2.25; MBMI-SDS = 1.26, SD = 1.50)
      completed the Food Cravings Questionnaire-Trait, then viewed pictures of high-
      and low-calorie foods and rated their liking for them, and subsequently consumed
      some of these foods in a bogus taste test. Contrary to expectations, higher body
      mass was associated with lower consumption of high-calorie foods. However, there
      was an interaction between body mass and trait food craving when predicting food
      consumption: in obese participants, higher trait food craving was associated with
      higher consumption of high-calorie foods and this association was not found in
      normal-weight participants. The relationship between trait food craving and high
      calorie food consumption within obese individuals was mediated by higher liking
      for high-calorie foods (but not by liking for low-calorie foods). Thus, similar
      to adults, a subgroup of obese children and adolescents - characterized by high
      trait food craving - seems to exist, calling for specific targeted treatment
      strategies.

PMID- 27708600
TI  - Attention Deficit/Hyperactivity Disorder (ADHD) Diagnosis: An Activation
      Executive Model.
AB  - Attention deficit with, or without, hyperactivity and impulsivity (ADHD) is
      categorized as neuro-developmental disorder. ADHD is a common disorder in
      childhood and one of the most frequent conditions affecting school ages. This
      disorder is characterized by a persistent behavioral pattern associated with
      inattention, over-activity (or hyperactivity), and difficulty in controlling
      impulses. Current research suggests the existence of certain patterns of cortical
      activation and executive control, which could more objectively identify ADHD.
      Through the use of a risk and resilience model, this research aimed to analyze
      the interaction between brain activation variables (nirHEG and Q-EEG) and
      executive variables (Continuous performance test -CPT-) in subjects with ADHD.
      The study involved 499 children, 175 females (35.1%) and 324 males (64.91%); aged
      from 6 to 16 years (M = 11.22, SD = 1.43). Two hundred and fifty six of the
      children had been diagnosed with Attention Deficit Hyperactivity Disorder (ADHD)
      and 243 were without ADHD. For the analysis of this objective, a causal model was
      designed to include the following different measures of task-execution: CPT TOVA
      (omissions, commissions, response time, variability, D prime and the ADHD Index);
      electrical activity (using Q-EEG); and blood-flow oxygenation activity (using
      nirHEG). The causal model was tested by means of structural equation modeling
      (SEM). The model that had been constructed was based upon three general
      assumptions: (1) There are different causal models for children with ADHD and
      those without ADHD; (2) The activation measures influence students' executive
      performance; and (3) There are measurable structural differences between the ADHD
      and control group models (executive and activation). In general, the results
      showed that: (a) activation measures influence executive patterns differently,
      (b) the relationship between activation variables (nirHEG and Q-EEG) depends on
      the brain zone being studied, (c) both groups showed important differences in
      variables correlation, with a good fit in each model (with and without ADHD).
      Lastly, the results were analyzed with a view to the diagnosis procedure.
      Therefore, we discuss the implications for future research.

PMID- 27708601
TI  - Gratitude and Adolescents' Subjective Well-Being in School: The Multiple
      Mediating Roles of Basic Psychological Needs Satisfaction at School.
AB  - Based on the relation between gratitude and general subjective well-being (SWB),
      and Basic Psychological Needs Theory (Ryan and Deci, 2000), the present study's
      aim was to use structural equation modeling to test the multiple mediational
      roles of the satisfaction of three basic psychological needs at school in
      accounting for the association between gratitude and SWB in school (school
      satisfaction, school affect) in adolescents. A total of 881 Chinese adolescents
      (427 males; Mean age = 12.97) completed a multi-measure questionnaire that tapped
      the targeted variables. Findings revealed that gratitude related significantly,
      positively to adolescents' SWB in school. Moreover, a multiple-mediators analysis
      suggested that relatedness and competence needs satisfaction at school mediated
      the relation between gratitude and SWB in school. Lastly, a multiple-mediators
      analysis also indicated that autonomy needs satisfaction mediated the relation
      between relatedness and competence needs and SWB in school. Limitations and
      practical applications of the study were discussed.

PMID- 27708602
TI  - The Bidirectional Effect between Momentary Affective States and Exercise Duration
      on a Day Level.
AB  - Despite the well-documented positive effect of exercise on health outcomes, most
      people do not succeed in exercising regularly. In addition to several other
      influences, affective states seem to support exercise participation. Associations
      between exercise and affect have been shown in the laboratory. However, the
      dynamic relation between affect and exercise in daily life is not yet well
      understood. The objective of this study was to investigate the bi-directional
      effect of momentary affective states on naturally occurring exercise and vice
      versa in healthy participants in real-life environments by applying an ecological
      momentary assessment design. We hypothesized that (1) exercise duration is
      positively associated with affective states on a day level, (2) affective states
      in the morning predict subsequent exercise duration, and (3) exercise duration
      predicts affective states in the evening on that respective day. Data from N = 60
      students aged between 19 and 32 years were analyzed. Affect and exercise duration
      were assessed daily over a period of 20 days via an electronic diary. Multilevel
      analysis revealed that positive affective valence was positively associated with
      exercise duration (p = 0.003) on a day level. In addition, the more the
      participants exercised that respective day, the better and more content they felt
      in the evening (p = 0.009). Energetic arousal in the morning significantly
      predicted subsequent exercise duration (p = 0.045). The findings indicate that it
      would be worthwhile to focus more on within-subject analyses when analyzing the
      dynamic relation between affect and exercise. Furthermore, affective states
      should be taken into account in creating effective interventions to foster
      exercise behavior and enhance maintenance.

PMID- 27708603
TI  - Engaging in Rather than Disengaging from Stress: Effective Coping and Perceived
      Control.
AB  - Being able to cope effectively with stress can help people to avoid negative
      consequences for their psychological well-being. The purpose of this study was to
      find out why some coping strategies are effective in reducing the negative effect
      of stressors on well-being and some are not. We argue that the degree to which
      such coping strategies engage or disengage people from stressful incidents is
      related to their perceived control of the situation that, in turn, is positively
      associated with their psychological well-being. We thus propose that the
      relationship between coping and psychological well-being is mediated by the
      extent of perceived sense of control. We collected cross-sectional data from a
      large heterogeneous sample (N = 543) in the Netherlands. We assessed seven
      different coping strategies, perceived control, and psychological well-being. Our
      results indeed revealed that strategies reflecting more engaged coping such as
      active confronting and reassuring thoughts, were associated with more sense of
      control and therefore to psychological well-being. In contrast, strategies
      reflecting disengagement coping, such as passive reaction pattern, palliative
      reaction, and avoidance, were associated with less perceived control, which in
      turn was negatively associated with psychological well-being. Results regarding
      the coping strategies expressing emotions and seeking social support were less
      straightforward, with the former being negatively associated with perceived
      control and psychological well-being, even though this strategy has stress
      engaging elements, and the latter only showing a positive indirect effect on
      psychological well-being via perceived control, but no positive main effect on
      well-being. These findings are discussed from the perspective of stress being an
      environment-perception-response process.

PMID- 27708604
TI  - Editorial: Hallucinations: New Interventions Supporting People with Distressing
      Voices and/or Visions.

PMID- 27708591
TI  - Cognitive Dysfunction, Affective States, and Vulnerability to Nicotine Addiction:
      A Multifactorial Perspective.
AB  - Although smoking prevalence has declined in recent years, certain subpopulations
      continue to smoke at disproportionately high rates and show resistance to
      cessation treatments. Individuals showing cognitive and affective impairments,
      including emotional distress and deficits in attention, memory, and inhibitory
      control, particularly in the context of psychiatric conditions, such as attention
      deficit hyperactivity disorder, schizophrenia, and mood disorders, are at higher
      risk for tobacco addiction. Nicotine has been shown to improve cognitive and
      emotional processing in some conditions, including during tobacco abstinence.
      Self-medication of cognitive deficits or negative affect has been proposed to
      underlie high rates of tobacco smoking among people with psychiatric disorders.
      However, pre-existing cognitive and mood disorders may also influence the
      development and maintenance of nicotine dependence, by biasing nicotine-induced
      alterations in information processing and associative learning, decision-making,
      and inhibitory control. Here, we discuss the potential forms of contribution of
      cognitive and affective deficits to nicotine addiction-related processes, by
      reviewing major clinical and preclinical studies investigating either the
      procognitive and therapeutic action of nicotine or the putative primary role of
      cognitive and emotional impairments in addiction-like features.

PMID- 27708608
TI  - Multimodal Integration of Spatial Information: The Influence of Object-Related
      Factors and Self-Reported Strategies.
AB  - Spatial representations are a result of multisensory information integration.
      More recent findings suggest that the multisensory information processing of a
      scene can be facilitated when paired with a semantically congruent auditory
      signal. This congruency effect was taken as evidence that audio-visual
      integration occurs for complex scenes. As navigation in our environment consists
      of a seamless integration of complex sceneries, a fundamental question arises:
      how is human landmark-based wayfinding affected by multimodality? In order to
      address this question, two experiments were conducted in a virtual environment.
      The first experiment compared wayfinding and landmark recognition performance in
      unimodal visual and acoustic landmarks. The second experiment focused on the
      congruency of multimodal landmark combinations and additionally assessed
      subject's self-reported strategies (i.e., whether they focused on direction
      sequences or landmarks). We demonstrate (1) the equality of acoustic and visual
      landmarks and (2) the congruency effect for the recognition of landmarks.
      Additionally, the results point out that self-reported strategies play a role and
      are an under-investigated topic in human landmark-based wayfinding.

PMID- 27708607
TI  - Editorial: Research Methods Pedagogy: Engaging Psychology Students in Research
      Methods and Statistics.

PMID- 27708605
TI  - Infants Encode Phonetic Detail during Cross-Situational Word Learning.
AB  - Infants often hear new words in the context of more than one candidate referent.
      In cross-situational word learning (XSWL), word-object mappings are determined by
      tracking co-occurrences of words and candidate referents across multiple learning
      events. Research demonstrates that infants can learn words in XSWL paradigms,
      suggesting that it is a viable model of real-world word learning. However, these
      studies have all presented infants with words that have no or minimal
      phonological overlap (e.g., BLICKET and GAX). Words often contain some degree of
      phonological overlap, and it is unknown whether infants can simultaneously encode
      fine phonological detail while learning words via XSWL. We tested 12-, 15-, 17-,
      and 20-month-olds' XSWL of eight words that, when paired, formed non-minimal
      pairs (MPs; e.g., BON-DEET) or MPs (e.g., BON-TON, DEET-DIT). The results
      demonstrated that infants are able to learn word-object mappings and encode them
      with sufficient phonetic detail as to identify words in both non-minimal and MP
      contexts. Thus, this work suggests that infants are able to simultaneously
      discriminate phonetic differences between words and map words to referents in an
      implicit learning paradigm such as XSWL.

PMID- 27708606
TI  - On the Phylogenesis of Executive Functions and Their Connection with Language
      Evolution.

PMID- 27708609
TI  - Team Synergies in Sport: Theory and Measures.
AB  - Individual players act as a coherent unit during team sports performance, forming
      a team synergy. A synergy is a collective property of a task-specific
      organization of individuals, such that the degrees of freedom of each individual
      in the system are coupled, enabling the degrees of freedom of different
      individuals to co-regulate each other. Here, we present an explanation for the
      emergence of such collective behaviors, indicating how these can be assessed and
      understood through the measurement of key system properties that exist,
      considering the contribution of each individual and beyond These include: to (i)
      dimensional compression, a process resulting in independent degree of freedom
      being coupled so that the synergy has fewer degrees of freedom than the set of
      components from which it arises; (ii) reciprocal compensation, if one element do
      not produce its function, other elements should display changes in their
      contributions so that task goals are still attained; (iii) interpersonal
      linkages, the specific contribution of each element to a group task; and (iv),
      degeneracy, structurally different components performing a similar, but not
      necessarily identical, function with respect to context. A primary goal of our
      analysis is to highlight the principles and tools required to understand coherent
      and dynamic team behaviors, as well as the performance conditions that make such
      team synergies possible, through perceptual attunement to shared affordances in
      individual performers. A key conclusion is that teams can be trained to perceive
      how to use and share specific affordances, explaining how individual's behaviors
      self-organize into a group synergy. Ecological dynamics explanations of team
      behaviors can transit beyond mere ratification of sport performance, providing a
      comprehensive conceptual framework to guide the implementation of diagnostic
      measures by sport scientists, sport psychologists and performance analysts.
      Complex adaptive systems, synergies, group behaviors, team sport performance,
      ecological dynamics, performance analysis.

PMID- 27708610
TI  - Patterns of Co-Occurring Gray Matter Concentration Loss across the Huntington
      Disease Prodrome.
AB  - Huntington disease (HD) is caused by an abnormally expanded cytosine-adenine
      guanine (CAG) trinucleotide repeat in the HTT gene. Age and CAG-expansion number
      are related to age at diagnosis and can be used to index disease progression.
      However, observed onset-age variability suggests that other factors also modulate
      progression. Indexing prodromal (pre-diagnosis) progression may highlight
      therapeutic targets by isolating the earliest-affected factors. We present the
      largest prodromal HD application of the univariate method voxel-based morphometry
      (VBM) and the first application of the multivariate method source-based
      morphometry (SBM) to, respectively, compare gray matter concentration (GMC) and
      capture co-occurring GMC patterns in control and prodromal participants. Using
      structural MRI data from 1050 (831 prodromal, 219 control) participants, we
      characterize control-prodromal, whole-brain GMC differences at various prodromal
      stages. Our results provide evidence for (1) regional co-occurrence and
      differential patterns of decline across the prodrome, with parietal and occipital
      differences commonly co-occurring, and frontal and temporal differences being
      relatively independent from one another, (2) fronto-striatal circuits being among
      the earliest and most consistently affected in the prodrome, (3) delayed
      degradation in some movement-related regions, with increasing subcortical and
      occipital differences with later progression, (4) an overall superior-to-inferior
      gradient of GMC reduction in frontal, parietal, and temporal lobes, and (5) the
      appropriateness of SBM for studying the prodromal HD population and its enhanced
      sensitivity to early prodromal and regionally concurrent differences.

PMID- 27708611
TI  - A History of Mild Traumatic Brain Injury Affects Peripheral Pulse Oximetry during
      Normobaric Hypoxia.
AB  - INTRODUCTION: Physiological and emotional stressors increase symptoms of
      concussion in recently injured individuals and both forms of stress-induced
      symptoms in people recovering from mild traumatic brain injury (mTBI), but who
      are asymptomatic when not stressed or are at rest. METHODS: Healthy asymptomatic
      adults (25.0 +/- 5.1 years) with a history of mTBI (n = 36) and matched healthy
      controls (HC) (n = 36) with no mTBI history were exposed to three levels of
      normobaric hypoxic stress generated with the Reduced Oxygen Breathing Device
      (ROBD) (Environics, Inc., Tollande, CT, USA), which reduced the percent O2 by
      mixing sea level air with nitrogen. The ROBD reduced the percent O2 in the
      breathable air from the normal 21% to 15.5% O2, 14% O2, and 13% O2. Under these
      conditions: (a) a standard pulse oximeter recorded peripheral oxygen saturation
      (SpO2) and pulse rate (beats per minute) and (b) the Functional Impairment Tester
      (FIT) (PMI, Inc., Rockville, MD, USA) recorded saccadic velocity and pupillary
      response dynamics to a brief light flash. RESULTS: For all three hypoxic stress
      conditions, the mTBI group had significantly higher SpO2 during the final minute
      of exposure than did the controls [F(2.17,151.8) = 5.29, p < 0.001, eta2 = 0.852]
      and the rate of SpO2 change over time was significantly shallower for the mTBI
      than for the controls [F(2.3,161.3) = 2.863, p < 0.001, eta2 = 0.569], Greenhouse
      Geisser corrected. Overall, mTBI had lower pulse rate but the difference was only
      significant for the 14% O2 condition. FIT oculomotor measures were not sensitive
      to group differences. When exposed to mild or moderate normobaric hypoxic stress
      (15% O2): (1) SpO2 differences emerged between the mTBI and matched HC groups,
      (2) heart rate trended lower in the mTBI group, and (3) FIT measures were not
      sensitive to group differences. CONCLUSION: A relatively minor hypoxic challenge
      can reveal measurable differences in SpO2 and heart rate in otherwise
      asymptomatic individuals with a history of mTBI.

PMID- 27708613
TI  - The Impact of MS-Related Cognitive Fatigue on Future Brain Parenchymal Loss and
      Relapse: A 17-Month Follow-up Study.
AB  - BACKGROUND: Fatigue is a disabling syndrome in multiple sclerosis (MS), which may
      be associated with inflammation and faster disease progression. OBJECTIVE: To
      analyze the significance of cognitive fatigue for subsequent disease progression.
      METHOD: We followed 46 MS patients and 14 healthy controls in a study over 17
      months. At the beginning (t1) and at the end (t2) of the study participants
      scored their fatigue, performed the Multiple Sclerosis Functional Composite and
      received MRI scanning, encompassing MPR T1, FLAIR, and DTI sequences. At t1, MS
      patients were divided into those with and those without cognitive fatigue (cut
      off score for moderate cognitive fatigue of the Fatigue Scale for Motor and
      Cognition). We calculated ANCOVAs for repeated measurement to analyze the
      relevance of cognitive fatigue status for the number of relapses and for MRI
      parameters. RESULTS: At t1, but not at t2, patients with cognitive fatigue showed
      increased axial and radial diffusivity of corpus callosum fibers. At t2, these
      patients showed significantly more loss of brain parenchyma and greater
      enlargement of lateral ventricles. Moreover, they developed more relapses, but
      there was no difference in lesion load or in performance deterioration.
      Additional analyses showed that only cognitive fatigue but not a more general
      score for fatigue (Fatigue Severity Scale) had an impact on the worsening of the
      disease status. CONCLUSION: Patients with cognitive fatigue may develop more
      brain atrophy and relapses during the next 17 months than patients without
      cognitive fatigue. Hence, experiencing cognitive fatigue might indicate more
      aggressive inflammatory processes and subsequent neurodegeneration.

PMID- 27708612
TI  - Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal
      Transcranial Direct Current Stimulation.
AB  - BACKGROUND: Fatigue in multiple sclerosis (MS) patients appears to correlate with
      vigilance decrement as reflected in an increase in reaction time (RT) and errors
      with prolonged time-on-task. OBJECTIVES: The aim of this study was to investigate
      whether anodal transcranial direct current stimulation (tDCS) over the right
      parietal or frontal cortex counteracts fatigue-associated vigilance decrement and
      subjective fatigue. METHODS: In study I, a randomized double-blind placebo
      controlled study, anodal tDCS (1.5 mA) was delivered to the right parietal cortex
      or the right frontal cortex of 52 healthy participants during the first 20 min of
      a 40-min lasting visual vigilance task. Study II, also a randomized double-blind
      placebo-controlled study, investigated the effect of anodal tDCS (1.5 mA) over
      the right parietal cortex in 46 MS patients experiencing cognitive fatigue. tDCS
      was delivered for 20 min before patients performed a 20-min lasting visual
      vigilance task. RESULTS: Study I showed that right parietal stimulation, but not
      right frontal stimulation, counteracts the increase in RT associated with
      vigilance decrement. Hence, only right parietal stimulation was applied to the MS
      patients in study II. Stimulation had a significant effect on vigilance decrement
      in mildly to moderately cognitively fatigued MS patients. Vigilance testing
      significantly increased the feeling of fatigue independent of stimulation.
      CONCLUSION: Anodal tDCS over the right parietal cortex can counteract the
      increase in RTs during vigilance performance, but not the increase in subjective
      fatigue. This finding is compatible with our model of fatigue in MS, suggesting a
      dissociation between the feeling and the behavioral characteristics of fatigue.

PMID- 27708614
TI  - Diving Response in Rats: Role of the Subthalamic Vasodilator Area.
AB  - Diving response (DR) is a powerful integrative response targeted toward survival
      of the hypoxic/anoxic conditions. Being present in all animals and humans, it
      allows to survive adverse conditions like diving. Earlier, we discovered that
      forehead stimulation affords neuroprotective effect, decreasing infarction volume
      triggered by permanent occlusion of the middle cerebral artery in rats. We
      hypothesized that cold stimulation of the forehead induces DR in rats, which, in
      turn, exerts neuroprotection. We compared autonomic [AP, heart rate (HR),
      cerebral blood flow (CBF)] and EEG responses to the known DR-triggering stimulus,
      ammonia stimulation of the nasal mucosa, cold stimulation of the forehead, and
      cold stimulation of the glabrous skin of the tail base in anesthetized rats.
      Responses in AP, HR, CBF, and EEG to cold stimulation of the forehead and ammonia
      vapors instillation into the nasal cavity were comparable and differed
      significantly from responses to the cold stimulation of the tail base.
      Excitotoxic lesion of the subthalamic vasodilator area (SVA), which is known to
      participate in CBF regulation and to afford neuroprotection upon excitation,
      failed to affect autonomic components of the DR evoked by forehead cold
      stimulation or nasal mucosa ammonia stimulation. We conclude that cold
      stimulation of the forehead triggers physiological response comparable to the
      response evoked by ammonia vapor instillation into nasal cavity, which is
      considered as stimulus triggering protective DR. These observations may explain
      the neuroprotective effect of the forehead stimulation. Data demonstrate that SVA
      does not directly participate in the autonomic adjustments accompanying DR;
      however, it is involved in diving-evoked modulation of EEG. We suggest that
      forehead stimulation can be employed as a stimulus capable of triggering oxygen
      conserving DR and can be used for neuroprotective therapy.

PMID- 27708615
TI  - Reduced Venous Compliance in Young Women with Type 1 Diabetes - Further
      Aggravated by Prolonged Elevated Levels of HbA1c.
AB  - BACKGROUND: Young patients with diabetes present with reduced compensatory
      responses to hypovolemic stress. Less compliant veins could be a contributing
      factor, since roughly two-thirds of the blood volume resides in the venous system
      as a blood reservoir, adjusting proper venous inflow to the heart. The aim of
      this study was to measure venous compliance and lower limb blood pooling during
      hypovolemic stress, and to correlate them to indices of diabetes severity and
      glucose control. METHODS: Fifteen young women with type 1 diabetes (DW) and 18
      healthy age-matched women (C) were subjected to lower body negative pressure
      (LBNP) (11-44 mmHg), creating hypovolemic stress. Lower limb blood pooling was
      measured with strain gage technique and venous compliance calculated as the
      relationship between ?V/?P. RESULTS: DW presented with reduced blood pooling
      (e.g., blood pooling during LBNP of 44 mmHg, DW, 1.69 +/- 0.10; C, 2.10 +/- 0.08
      (ml/100 ml), and P = 0.003). Calculated venous compliance was also reduced in DW
      (e.g., compliance at 20 mmHg, DW, 0.046 +/- 0.003; C, 0.059 +/- 0.002 (ml/100
      ml/mmHg), and P = 0.002). A progressive reduction in both venous compliance (P <
      0.007) and blood pooling (P < 0.005) was seen with increasing level of HbA1c, and
      furthermore, less strongly associated with presence of microvascular disease
      (signs of retinopathy). CONCLUSION: Women with type 1 diabetes present with both
      reduced venous compliance and blood pooling. The reductions were particularly
      present in patients with long-standing poor glycemic control.

PMID- 27708617
TI  - Increased Circulating Adiponectin in Response to Thiazolidinediones:
      Investigating the Role of Bone Marrow Adipose Tissue.
AB  - BACKGROUND: Bone marrow adipose tissue (MAT) contributes to increased circulating
      adiponectin, an insulin-sensitizing hormone, during caloric restriction (CR), but
      whether this occurs in other contexts remains unknown. The antidiabetic
      thiazolidinediones (TZDs) also promote MAT expansion and hyperadiponectinemia,
      even without increasing adiponectin expression in white adipose tissue (WAT).
      OBJECTIVES: To test the hypothesis that MAT expansion contributes to TZD
      associated hyperadiponectinemia, we investigated the effects of rosiglitazone, a
      prototypical TZD, in wild-type (WT) or Ocn-Wnt10b mice. The latter resist MAT
      expansion during CR, leading us to postulate that they would also resist this
      effect of rosiglitazone. DESIGN: Male and female WT or Ocn-Wnt10b mice (C57BL/6J)
      were treated with or without rosiglitazone for 2, 4, or 8 weeks, up to 30 weeks
      of age. MAT content was assessed by osmium tetroxide staining and adipocyte
      marker expression. Circulating adiponectin was determined by ELISA. RESULTS: In
      WT mice, rosiglitazone caused hyperadiponectinemia and MAT expansion. Compared to
      WT mice, Ocn-Wnt10b mice had significantly less MAT in distal tibiae and
      sometimes in proximal tibiae; however, interpretation was complicated by the
      leakage of osmium tetroxide from ruptures in some tibiae, highlighting an
      important technical consideration for osmium-based MAT analysis. Despite
      decreased MAT in Ocn-Wnt10b mice, circulating adiponectin was generally similar
      between WT and Ocn-Wnt10b mice; however, in females receiving rosiglitazone for 4
      weeks, hyperadiponectinemia was significantly blunted in Ocn-Wnt10b compared to
      WT mice. Notably, this was also the only group in which tibial adiponectin
      expression was lower than in WT mice, suggesting a close association between MAT
      adiponectin production and circulating adiponectin. However, rosiglitazone
      significantly increased adiponectin protein expression in WAT, suggesting that
      WAT contributes to hyperadiponectinemia in this context. Finally, rosiglitazone
      upregulated uncoupling protein 1 in brown adipose tissue (BAT), but this protein
      was undetectable in tibiae, suggesting that MAT is unlikely to share thermogenic
      properties of BAT. CONCLUSION: TZD-induced hyperadiponectinemia is closely
      associated with increased adiponectin production in MAT but is not prevented by
      the partial loss of MAT that occurs in Ocn-Wnt10b mice. Thus, more robust loss-of
      MAT models are required for future studies to better establish MAT's elusive
      functions, both on an endocrine level and beyond.

PMID- 27708618
TI  - The Underexploited Role of Non-Coding RNAs in Lysosomal Storage Diseases.
AB  - Non-coding RNAs (ncRNAs) are a functional class of RNA involved in the regulation
      of several cellular processes which may modulate disease onset, progression, and
      prognosis. Lysosomal storage diseases (LSD) are a group of rare disorders caused
      by mutations of genes encoding specific hydrolases or non-enzymatic proteins,
      characterized by a wide spectrum of manifestations. The alteration of ncRNA
      levels is well established in several human diseases such as cancer and auto
      immune disorders; however, there is a lack of information focused on the role of
      ncRNA in rare diseases. Recent reports related to changes in ncRNA expression and
      its consequences on LSD physiopathology show us the importance to keep advancing
      in this field. This article will summarize recent findings and provide key points
      for further studies on LSD and ncRNA association.

PMID- 27708616
TI  - The Bone Marrow-Derived Stromal Cells: Commitment and Regulation of Adipogenesis.
AB  - Bone marrow (BM) microenvironment represents an important compartment of bone
      that regulates bone homeostasis and the balance between bone formation and bone
      resorption depending on the physiological needs of the organism. Abnormalities of
      BM microenvironmental dynamics can lead to metabolic bone diseases. BM stromal
      cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal
      stem cell (BMSC)] are multipotent stem cells located within BM stroma and give
      rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of
      BMSC lineage commitment to adipocytic lineage and regulation of BM adipocyte
      formation are not fully understood. In this review, we will discuss recent
      findings pertaining to identification and characterization of adipocyte
      progenitor cells in BM and the regulation of differentiation into mature
      adipocytes. We have also emphasized the clinical relevance of these findings.

PMID- 27708619
TI  - Epidemiological and Genomic Landscape of Azole Resistance Mechanisms in
      Aspergillus Fungi.
AB  - Invasive aspergillosis is a life-threatening mycosis caused by the pathogenic
      fungus Aspergillus. The predominant causal species is Aspergillus fumigatus, and
      azole drugs are the treatment of choice. Azole drugs approved for clinical use
      include itraconazole, voriconazole, posaconazole, and the recently added
      isavuconazole. However, epidemiological research has indicated that the
      prevalence of azole-resistant A. fumigatus isolates has increased significantly
      over the last decade. What is worse is that azole-resistant strains are likely to
      have emerged not only in response to long-term drug treatment but also because of
      exposure to azole fungicides in the environment. Resistance mechanisms include
      amino acid substitutions in the target Cyp51A protein, tandem repeat sequence
      insertions at the cyp51A promoter, and overexpression of the ABC transporter
      Cdr1B. Environmental azole-resistant strains harboring the association of a
      tandem repeat sequence and punctual mutation of the Cyp51A gene (TR34/L98H and
      TR46/Y121F/T289A) have become widely disseminated across the world within a short
      time period. The epidemiological data also suggests that the number of
      Aspergillus spp. other than A. fumigatus isolated has risen. Some non-fumigatus
      species intrinsically show low susceptibility to azole drugs, imposing the need
      for accurate identification, and drug susceptibility testing in most clinical
      cases. Currently, our knowledge of azole resistance mechanisms in non-fumigatus
      Aspergillus species such as A. flavus, A. niger, A. tubingensis, A. terreus, A.
      fischeri, A. lentulus, A. udagawae, and A. calidoustus is limited. In this
      review, we present recent advances in our understanding of azole resistance
      mechanisms particularly in A. fumigatus. We then provide an overview of the
      genome sequences of non-fumigatus species, focusing on the proteins related to
      azole resistance mechanisms.

PMID- 27708620
TI  - Beneficial Effects of Spices in Food Preservation and Safety.
AB  - Spices have been used since ancient times. Although they have been employed
      mainly as flavoring and coloring agents, their role in food safety and
      preservation have also been studied in vitro and in vivo. Spices have exhibited
      numerous health benefits in preventing and treating a wide variety of diseases
      such as cancer, aging, metabolic, neurological, cardiovascular, and inflammatory
      diseases. The present review aims to provide a comprehensive summary of the most
      relevant and recent findings on spices and their active compounds in terms of
      targets and mode of action; in particular, their potential use in food
      preservation and enhancement of shelf life as a natural bioingredient.

PMID- 27708621
TI  - Reassessment of the Enteropathogenicity of Mesophilic Aeromonas Species.
AB  - Cases of Aeromonas diarrhea have been described all over the world. The genus
      Aeromonas includes ca. 30 species, of which 10 have been isolated in association
      with gastroenteritis. The dominating species that account for ca. 96% of the
      identified strains are Aeromonas caviae, A. veronii, A. dhakensis, and A.
      hydrophila. However, the role of Aeromonas as a true enteropathogen has been
      questioned on the basis of the lack of outbreaks, the non-fulfillment of Koch's
      postulates and the low numbers of acute illnesses in the only existing human
      challenge study. In the present study we reassess the enteropathogenicity of
      Aeromonas using dose response models for microbial infection and acute illness.
      The analysis uses the data from the human challenge study and additional data
      from selected outbreak investigations where the numbers exposed and the dose were
      reported, allowing their inclusion as "natural experiments". In the challenge
      study several cases of asymptomatic shedding were found (26.3%, 15/57), however,
      only 3.5% (2/57) of those challenged with Aeromonas developed acute enteric
      symptoms (i.e., diarrhea). The "natural experiments" showed a much higher risk of
      illness associated with exposure to Aeromonas, even at moderate to low doses. The
      median dose required for 1% illness risk, was ~1.4 * 104 times higher in the
      challenge study (1.24 * 104 cfu) compared to natural exposure events (0.9 cfu).
      The dose response assessment presented in this study shows that the combined
      challenge and outbreak data are consistent with high infectivity of Aeromonas,
      and a wide range of susceptibility to acute enteric illness. To illustrate the
      outcomes, we simulate the risk associated with concentrations of Aeromonas found
      in different water and food matrices, indicating the disease burden potentially
      associated with these bacteria. In conclusion this study showed that Aeromonas is
      highly infectious, and that human susceptibility to illness may be high, similar
      to undisputed enteropathogens like Campylobacter or Salmonella.

PMID- 27708622
TI  - Antibacterial Activities of Wasabi against Escherichia coli O157:H7 and
      Staphylococcus aureus.
AB  - Escherichia coli O157:H7 and Staphylococcus aureus are two of the major pathogens
      frequently involved in foodborne outbreaks. Control of these pathogens in foods
      is essential to food safety. It is of great interest in the use of natural
      antimicrobial compounds present in edible plants to control foodborne pathogens
      as consumers prefer more natural "green" foods. Allyl isothiocyanate (AITC) is an
      antimicrobial compound naturally present in wasabi (Japanese horseradish) and
      several other edible plants. Although the antibacterial effects of pure AITC and
      wasabi extract (essential oil) against several bacteria have been reported, the
      antibacterial property of natural wasabi has not been well studied. This study
      investigated the antibacterial activities of wasabi as well as AITC against E.
      coli O157:H7 and S. aureus. Chemical analysis showed that AITC is the major
      isothiocyanate in wasabi. The AITC concentration in the wasabi powder used in
      this study was 5.91 +/- 0.59 mg/g. The minimum inhibitory concentration (MIC) of
      wasabi against E. coli O157:H7 or S. aureus was 1% (or 10 mg/ml). Wasabi at 4%
      displayed higher bactericidal activity against S. aureus than against E. coli
      O157:H7. The MIC of AITC against either pathogen was between 10 and 100 MUg/ml.
      AITC at 500 MUg/ml was bactericidal against both pathogens while AITC at 1000
      MUg/ml eliminated E. coli O157:H7 much faster than S. aureus. The results from
      this study showed that wasabi has strong antibacterial property and has high
      potential to effectively control E. coli O157:H7 and S. aureus in foods. The
      antibacterial property along with its natural green color, unique flavor, and
      advantage to safeguard foods at the point of ingestion makes wasabi a promising
      natural edible antibacterial plant. The results from this study may be of
      significant interest to the food industry as they develop new and safe foods.
      These results may also stimulate more research to evaluate the antibacterial
      effect of wasabi against other foodborne pathogens and to explore other edible
      plants for their antimicrobial properties. To our knowledge, this is the first
      report on the antibacterial activity of wasabi in its natural form of consumption
      against E. coli O157:H7 and S. aureus.

PMID- 27708624
TI  - The Probiotic Butyricicoccus pullicaecorum Reduces Feed Conversion and Protects
      from Potentially Harmful Intestinal Microorganisms and Necrotic Enteritis in
      Broilers.
AB  - Probiotics which do not result in the development and spread of microbial
      resistance are among the candidate replacements for antibiotics previously used
      as growth promotors. In this study the effect of in-feed supplementation of the
      butyrate producing Butyricicoccus pullicaecorum strain 25-3T on performance,
      intestinal microbiota and prevention of necrotic enteritis (NE), a disease caused
      by Clostridium perfringens was evaluated in broilers. For the performance study,
      day old Ross 308 chicks were randomly allocated into two treatment groups and fed
      either a non-supplemented diet or a diet supplemented with 109 cfu lyophilized B.
      pullicaecorum per kg feed for 40 days. On day 40 broilers administered B.
      pullicaecorum had a significant lower bodyweight (2675 g vs. 2762 g; p = 0.0025)
      but supplementation of B. pullicaecorum decreased the feed conversion ratio
      significantly (1.518 vs. 1.632; p < 0.0001). Additionally, ingestion of the
      Butyricicoccus strain significantly lowered the abundance of Campylobacter spp.
      in the caecum and Enterococcus and Escherichia/Shigella spp. in the ileum at day
      40. In feed supplementation of B. pullicaecorum in the NE trials resulted in a
      significant decrease in the number of birds with necrotic lesions compared with
      the untreated control group. These studies show that supplementation of B.
      pullicaecorum is able to improve feed conversion, to reduce the abundance of some
      potentially important pathogens in the caeca and ileum and to contribute to the
      prevention of NE in broilers, making the strain a potential valuable probiotic.

PMID- 27708623
TI  - Biostimulation of Indigenous Microbial Community for Bioremediation of Petroleum
      Refinery Sludge.
AB  - Nutrient deficiency severely impairs the catabolic activity of indigenous
      microorganisms in hydrocarbon rich environments (HREs) and limits the rate of
      intrinsic bioremediation. The present study aimed to characterize the microbial
      community in refinery waste and evaluate the scope for biostimulation based in
      situ bioremediation. Samples recovered from the wastewater lagoon of Guwahati
      refinery revealed a hydrocarbon enriched [high total petroleum hydrocarbon
      (TPH)], oxygen-, moisture-limited, reducing environment. Intrinsic biodegradation
      ability of the indigenous microorganisms was enhanced significantly (>80%
      reduction in TPH by 90 days) with nitrate amendment. Preferred utilization of
      both higher- (>C30) and middle- chain (C20-30) length hydrocarbons were evident
      from GC-MS analysis. Denaturing gradient gel electrophoresis and community level
      physiological profiling analyses indicated distinct shift in community's
      composition and metabolic abilities following nitrogen (N) amendment. High
      throughput deep sequencing of 16S rRNA gene showed that the native community was
      mainly composed of hydrocarbon degrading, syntrophic, methanogenic,
      nitrate/iron/sulfur reducing facultative anaerobic bacteria and archaebacteria,
      affiliated to gamma- and delta-Proteobacteria and Euryarchaeota respectively.
      Genes for aerobic and anaerobic alkane metabolism (alkB and bssA), methanogenesis
      (mcrA), denitrification (nirS and narG) and N2 fixation (nifH) were detected.
      Concomitant to hydrocarbon degradation, lowering of dissolve O2 and increase in
      oxidation-reduction potential (ORP) marked with an enrichment of N2 fixing,
      nitrate reducing aerobic/facultative anaerobic members [e.g., Azovibrio,
      Pseudoxanthomonas and Comamonadaceae members] was evident in N amended microcosm.
      This study highlighted that indigenous community of refinery sludge was
      intrinsically diverse, yet appreciable rate of in situ bioremediation could be
      achieved by supplying adequate N sources.

PMID- 27708625
TI  - Development of an in vitro Assay, Based on the BioFilm Ring Test(r), for Rapid
      Profiling of Biofilm-Growing Bacteria.
AB  - Microbial biofilm represents a major virulence factor associated with chronic and
      recurrent infections. Pathogenic bacteria embedded in biofilms are highly
      resistant to environmental and chemical agents, including antibiotics and
      therefore difficult to eradicate. Thus, reliable tests to assess biofilm
      formation by bacterial strains as well as the impact of chemicals or antibiotics
      on biofilm formation represent desirable tools for a most effective therapeutic
      management and microbiological risk control. Current methods to evaluate biofilm
      formation are usually time-consuming, costly, and hardly applicable in the
      clinical setting. The aim of the present study was to develop and assess a simple
      and reliable in vitro procedure for the characterization of biofilm-producing
      bacterial strains for future clinical applications based on the BioFilm Ring
      Test(r) (BRT) technology. The procedure developed for clinical testing (cBRT) can
      provide an accurate and timely (5 h) measurement of biofilm formation for the
      most common pathogenic bacteria seen in clinical practice. The results gathered
      by the cBRT assay were in agreement with the traditional crystal violet (CV)
      staining test, according to the kappa coefficient test (kappa = 0.623). However,
      the cBRT assay showed higher levels of specificity (92.2%) and accuracy (88.1%)
      as compared to CV. The results indicate that this procedure offers an easy, rapid
      and robust assay to test microbial biofilm and a promising tool for clinical
      microbiology.

PMID- 27708626
TI  - From Mouth to Model: Combining in vivo and in vitro Oral Biofilm Growth.
AB  - Background: Oral biofilm studies based on simplified experimental setups are
      difficult to interpret. Models are limited mostly by the number of bacterial
      species observed and the insufficiency of artificial media. Few studies have
      attempted to overcome these limitations and to cultivate native oral biofilm.
      Aims: This study aimed to grow oral biofilm in vivo before transfer to a biofilm
      reactor for ex situ incubation. The in vitro survival of this oral biofilm and
      the changes in bacterial composition over time were observed. Methods: Six human
      enamel-dentin slabs embedded buccally in dental splints were used as biofilm
      carriers. Fitted individually to the upper jaw of 25 non-smoking male volunteers,
      the splints were worn continuously for 48 h. During this time, tooth-brushing and
      alcohol-consumption were not permitted. The biofilm was then transferred on slabs
      into a biofilm reactor and incubated there for 48 h while being nourished in BHI
      medium. Live/dead staining and confocal laser scanning microscopy were used to
      observe bacterial survival over four points in time: directly after removal (T0)
      and after 1 (T1), 24 (T2), and 48 h (T3) of incubation. Bacterial diversity at T0
      and T3 was compared with 454-pyrosequencing. Fluorescence in situ hybridization
      (FISH) was performed to show specific taxa. Survival curves were calculated with
      a specially designed MATLAB script. Acacia and QIIME 1.9.1 were used to process
      pyrosequencing data. SPSS 21.0 and R 3.3.1 were used for statistical analysis.
      Results: After initial fluctuations at T1, survival curves mostly showed
      approximation of the bacterial numbers to the initial level at T3. Pyrosequencing
      analysis resulted in 117 OTUs common to all samples. The genera Streptococcus and
      Veillonella (both Firmicutes) dominated at T0 and T3. They make up two thirds of
      the biofilm. Genera with lower relative abundance had grown significantly at T3.
      FISH analysis confirmed the pyrosequencing results, i.e., the predominant
      staining of Firmicutes. Conclusion: We demonstrate the in vitro survival of
      native primary oral biofilm in its natural complexity over 48 h. Our results
      offer a baseline for cultivation studies of native oral biofilms in (phyto-)
      pharmacological and dental materials research. Further investigations and
      validation of culturing conditions could also facilitate the study of biofilm
      induced diseases.

PMID- 27708627
TI  - A Phenotypic and Genotypic Analysis of the Antimicrobial Potential of Cultivable
      Streptomyces Isolated from Cave Moonmilk Deposits.
AB  - Moonmilk speleothems of limestone caves host a rich microbiome, among which
      Actinobacteria represent one of the most abundant phyla. Ancient medical texts
      reported that moonmilk had therapeutical properties, thereby suggesting that its
      filamentous endemic actinobacterial population might be a source of natural
      products useful in human treatment. In this work, a screening approach was
      undertaken in order to isolate cultivable Actinobacteria from moonmilk of the
      Grotte des Collemboles in Belgium, to evaluate their taxonomic profile, and to
      assess their potential in biosynthesis of antimicrobials. Phylogenetic analysis
      revealed that all 78 isolates were exclusively affiliated to the genus
      Streptomyces and clustered into 31 distinct phylotypes displaying various
      pigmentation patterns and morphological features. Phylotype representatives were
      tested for antibacterial and antifungal activities and their genomes were mined
      for secondary metabolite biosynthetic genes coding for non-ribosomal peptide
      synthetases (NRPSs), and polyketide synthases (PKS). The moonmilk Streptomyces
      collection was found to display strong inhibitory activities against a wide range
      of reference organisms, as 94, 71, and 94% of the isolates inhibited or impaired
      the growth of Gram-positive, Gram-negative bacteria, and fungi, respectively.
      Interestingly, 90% of the cave strains induced strong growth suppression against
      the multi-drug resistant Rasamsonia argillacea, a causative agent of invasive
      mycosis in cystic fibrosis and chronic granulomatous diseases. No correlation was
      observed between the global antimicrobial activity of an individual strain and
      the number of NRPS and PKS genes predicted in its genome, suggesting that
      approaches for awakening cryptic metabolites biosynthesis should be applied to
      isolates with no antimicrobial phenotype. Overall, our work supports the common
      belief that moonmilk might effectively treat various infectious diseases thanks
      to the presence of a highly diverse population of prolific antimicrobial
      producing Streptomyces, and thus may indeed constitute a promising reservoir of
      potentially novel active natural compounds.

PMID- 27708628
TI  - Quantitative Proteomic Analysis of Germination of Nosema bombycis Spores under
      Extremely Alkaline Conditions.
AB  - The microsporidian Nosema bombycis is an obligate intracellular pathogen of the
      silkworm Bombyx mori, causing the epidemic disease Pebrine and extensive economic
      losses in sericulture. Although N. bombycis forms spores with rigid spore walls
      that protect against various environmental pressures, ingested spores germinate
      immediately under the extremely alkaline host gut condition (Lepidoptera gut pH >
      10.5), which is a key developmental turning point from dormant state to infected
      state. However, to date this process remains poorly understood due to the
      complexity of the animal digestive tract and the lack of genetic tools for
      microsporidia. Here we show, using an in vitro spore germination model, how the
      proteome of N. bombycis changes during germination, analyse specific metabolic
      pathways employed in detail, and validate key functional proteins in vivo in
      silkworms. By a label-free quantitative proteomics approach that is directly
      based on high-resolution mass spectrometry (MS) data, a total of 1136 proteins
      were identified with high confidence, with 127 proteins being significantly
      changed in comparison to non-germinated spores. Among them, structural proteins
      including polar tube protein 1 and 3 and spore wall protein (SWP) 4 and 30 were
      found to be significantly down-regulated, but SWP9 significantly up-regulated.
      Some nucleases like polynucleotide kinase/phosphatase and flap endonucleases 1,
      together with a panel of hydrolases involved in protein degradation and RNA
      cleavage were overrepresented too upon germination, which implied that they might
      play important roles during spore germination. The differentially regulated
      trends of these genes were validated, respectively, by quantitative RT-PCR and 3
      proteins of interest were confirmed by Western blotting analyses in vitro and in
      vivo. Furthermore, the pathway analysis showed that abundant up- and down
      regulations appear involved in the glycolysis, pentose phosphate pathway, purine,
      and pyrimidine metabolism, suggesting preparations of energy generation and
      substance synthesis for the following invasion and proliferation inside the host.
      This report, to our knowledge, provides the first proteomic landscape of N.
      bombycis spores, and also a stepping stone on the way to further study of the
      unique infection mode of this economically important pathogen and other
      microsporidia in general.

PMID- 27708629
TI  - Upstream Freshwater and Terrestrial Sources Are Differentially Reflected in the
      Bacterial Community Structure along a Small Arctic River and Its Estuary.
AB  - Glacier melting and altered precipitation patterns influence Arctic freshwater
      and coastal ecosystems. Arctic rivers are central to Arctic water ecosystems by
      linking glacier meltwaters and precipitation with the ocean through transport of
      particulate matter and microorganisms. However, the impact of different water
      sources on the microbial communities in Arctic rivers and estuaries remains
      unknown. In this study we used 16S rRNA gene amplicon sequencing to assess a
      small river and its estuary on the Disko Island, West Greenland (69 degrees N).
      Samples were taken in August when there is maximum precipitation and temperatures
      are high in the Disko Bay area. We describe the bacterial community through a
      river into the estuary, including communities originating in a glacier and a
      proglacial lake. Our results show that water from the glacier and lake transports
      distinct communities into the river in terms of diversity and community
      composition. Bacteria of terrestrial origin were among the dominating OTUs in the
      main river, while the glacier and lake supplied the river with water containing
      fewer terrestrial organisms. Also, more psychrophilic taxa were found in the
      community supplied by the lake. At the river mouth, the presence of dominant
      bacterial taxa from the lake and glacier was unnoticeable, but these taxa
      increased their abundances again further into the estuary. On average 23% of the
      estuary community consisted of indicator OTUs from different sites along the
      river. Environmental variables showed only weak correlations with community
      composition, suggesting that hydrology largely influences the observed patterns.

PMID- 27708631
TI  - Suspension Array for Multiplex Detection of Eight Fungicide-Resistance Related
      Alleles in Botrytis cinerea.
AB  - A simple and high-throughput assay to detect fungicide resistance is required for
      large-scale monitoring of the emergence of resistant strains of Botrytis cinerea.
      Using suspension array technology performed on a Bio-Plex 200 System, we
      developed a single-tube allele-specific primer extension assay that can
      simultaneously detect eight alleles in one reaction. These eight alleles include
      E198 and 198A of the beta-Tubulin gene (BenA), H272 and 272Y of the Succinate
      dehydrogenase iron-sulfur subunit gene (SdhB), I365 and 365S of the putative
      osmosensor histidine kinase gene (BcOS1), and F412 and 412S of the 3
      ketoreductase gene (erg27). This assay was first established and optimized with
      eight plasmid templates containing the DNA sequence variants BenA-E198, BenA
      198A, SdhB-H272, SdhB-272Y, BcOS1-I365, BcOS1-365S, erg27-F412, and erg27-412S.
      Results indicated that none of the probes showed cross-reactivity with one
      another. The minimum limit of detection for these genotypes was one copy per
      test. Four mutant plasmids were mixed with 10 ng/MUL wild-type genomic DNA in
      different ratios. Detection sensitivity of mutant loci was 0.45% for BenA-E198A,
      BcOS1-I365S, and erg27-F412S, and was 4.5% for SdhB-H272Y. A minimum quantity of
      0.1 ng of genomic DNA was necessary to obtain reliable results. This is the first
      reported assay that can simultaneously detect mutations in BenA, SdhB, BcOS1, and
      erg27.

PMID- 27708630
TI  - Beyond 16S rRNA Community Profiling: Intra-Species Diversity in the Gut
      Microbiota.
AB  - Interactions with microbes affect many aspects of animal biology, including
      immune system development, nutrition and health. In vertebrates, the gut
      microbiota is dominated by a small subset of phyla, but the species composition
      within these phyla is typically not conserved. Moreover, several recent studies
      have shown that bacterial species in the gut are composed of a multitude of
      strains, which frequently co-exist in their host, and may be host-specific.
      However, since the study of intra-species diversity is challenging, particularly
      in the setting of complex, host-associated microbial communities, our current
      understanding of the distribution, evolution and functional relevance of intra
      species diversity in the gut is scarce. In order to unravel how genomic diversity
      translates into phenotypic diversity, community analyses going beyond 16S rRNA
      profiling, in combination with experimental approaches, are needed. Recently, the
      honeybee has emerged as a promising model for studying gut bacterial communities,
      particularly in terms of strain-level diversity. Unlike most other invertebrates,
      the honeybee gut is colonized by a remarkably consistent and specific core
      microbiota, which is dominated by only eight bacterial species. As for the
      vertebrate gut microbiota, these species are composed of highly diverse strains
      suggesting that similar evolutionary forces shape gut community structures in
      vertebrates and social insects. In this review, we outline current knowledge on
      the evolution and functional relevance of strain diversity within the gut
      microbiota, including recent insights gained from mammals and other animals such
      as the honeybee. We discuss methodological approaches and propose possible future
      avenues for studying strain diversity in complex bacterial communities.

PMID- 27708633
TI  - Persistent Infection by Wolbachia wAlbB Has No Effect on Composition of the Gut
      Microbiota in Adult Female Anopheles stephensi.
AB  - The bacteria in the midgut of Anopheles stephensi adult females from laboratory
      colonies were studied by sequencing the V4 region of 16S rRNA genes, with respect
      to three experimental factors: stable or cured Wolbachia infection; sugar or
      blood diet; and age. Proteobacteria and Bacteroidetes dominated the community
      [>90% of operational taxonomic units (OTUs)]; most taxa were in the classes
      Flavobacteriia, Gammaproteobacteria, and Alphaproteobacteria, and were assigned
      to Elizabethkingia (46.9%), Asaia (6.4%) and Pseudomonas (6.0%), or unclassified
      Enterobacteriaceae (37.2%). Bacterial communities were similar between Wolbachia
      cured and Wolbachia-infected mosquito lines, indicating that the gut microbiota
      were not dysregulated in the presence of Wolbachia. The proportion of
      Enterobacteriaceae was higher in mosquitoes fed a blood meal compared to those
      provided a sugar meal. Collectively, the bacterial community had a similar
      structure in older Wolbachia-infected mosquitoes 8 days after the blood meal, as
      in younger Wolbachia-infected mosquitoes before a blood meal, except that older
      mosquitoes had a higher proportion of Enterobacteriaceae and lower proportion of
      Elizabethkingia. Consistent presence of certain predominant bacteria
      (Elizabethkingia, Asaia, Pseudomonas, and Enterobacteriaceae) suggests they would
      be useful for paratransgenesis to control malaria infection, particularly when
      coupled to a Wolbachia-based intervention strategy.

PMID- 27708634
TI  - Localization of Components of the RNA-Degrading Machine in Bacillus subtilis.
AB  - In bacteria, the control of mRNA stability is crucial to allow rapid adaptation
      to changing conditions. In most bacteria, RNA degradation is catalyzed by the RNA
      degradosome, a protein complex composed of endo- and exoribonucleases, RNA
      helicases, and accessory proteins. In the Gram-positive model organism Bacillus
      subtilis, the existence of a RNA degradosome assembled around the membrane-bound
      endoribonuclease RNase Y has been proposed. Here, we have studied the
      intracellular localization of the protein that have been implicated in the
      potential B. subtilis RNA degradosome, i.e., polynucleotide phosphorylase, the
      exoribonucleases J1 and J2, the DEAD-box RNA helicase CshA, and the glycolytic
      enzymes enolase and phosphofructokinase. Our data suggests that the bulk of these
      enzymes is located in the cytoplasm. The RNases J1 and J2 as well as the RNA
      helicase CshA were mainly localized in the peripheral regions of the cell where
      also the bulk of messenger RNA is localized. We were able to demonstrate active
      exclusion of these proteins from the transcribing nucleoid. Taken together, our
      findings suggest that the interactions of the enzymes involved in RNA degradation
      in B. subtilis are rather transient.

PMID- 27708636
TI  - Genome Sequence of Vibrio parahaemolyticus VP103 Strain Isolated from Shrimp in
      Malaysia.

PMID- 27708632
TI  - Multidrug Efflux Pumps at the Crossroad between Antibiotic Resistance and
      Bacterial Virulence.
AB  - Multidrug efflux pumps can be involved in bacterial resistance to antibiotics at
      different levels. Some efflux pumps are constitutively expressed at low levels
      and contribute to intrinsic resistance. In addition, their overexpression may
      allow higher levels of resistance. This overexpression can be transient, in the
      presence of an effector (phenotypic resistance), or constitutive when mutants in
      the regulatory elements of the expression of efflux pumps are selected (acquired
      resistance). Efflux pumps are present in all cells, from human to bacteria and
      are highly conserved, which indicates that they are ancient elements in the
      evolution of different organisms. Consequently, it has been suggested that,
      besides antibiotic resistance, bacterial multidrug efflux pumps would likely
      contribute to other relevant processes of the microbial physiology. In the
      current article, we discuss some specific examples of the role that efflux pumps
      may have in the bacterial virulence of animals' and plants' pathogens, including
      the processes of intercellular communication. Based in these evidences, we
      propose that efflux pumps are at the crossroad between resistance and virulence
      of bacterial pathogens. Consequently, the comprehensive study of multidrug efflux
      pumps requires addressing these functions, which are of relevance for the
      bacterial-host interactions during infection.

PMID- 27708635
TI  - The Kinome of Edible and Medicinal Fungus Wolfiporia cocos.
AB  - Wolfiporia cocos is an edible and medicinal fungus that grows in association with
      pine trees, and its dried sclerotium, known as Fuling in China, has been used as
      a traditional medicine in East Asian countries for centuries. Nearly 10% of the
      traditional Chinese medicinal preparations contain W. cocos. Currently, the
      commercial production of Fuling is limited because of the lack of pine-based
      substrate and paucity of knowledge about the sclerotial development of the
      fungus. Since protein kinase (PKs) play significant roles in the regulation of
      growth, development, reproduction, and environmental responses in filamentous
      fungi, the kinome of W. cocos was analyzed by identifying the PKs genes, studying
      transcript profiles and assigning PKs to orthologous groups. Of the 10 putative
      PKs, 11 encode atypical PKs, and 13, 10, 2, 22, and 11 could encoded PKs from the
      AGC, CAMK, CK, CMGC, STE, and TLK Groups, respectively. The level of transcripts
      from PK genes associated with sclerotia formation in the mycelium and sclerotium
      stages were analyzed by qRT-PCR. Based on the functions of the orthologs in
      Sclerotinia sclerotiorum (a sclerotia-formation fungus) and Saccharomyces
      cerevisiae, the potential roles of these W. cocos PKs were assigned. To the best
      of our knowledge, our study is the first identification and functional discussion
      of the kinome in the edible and medicinal fungus W. cocos. Our study
      systematically suggests potential roles of W. cocos PKs and provide comprehensive
      and novel insights into W. cocos sclerotial development and other economically
      important traits. Additionally, based on our result, genetic engineering can be
      employed for over expression or interference of some significant PKs genes to
      promote sclerotial growth and the accumulation of active compounds.

PMID- 27708637
TI  - Microbiome Dynamics of a Polychlorobiphenyl (PCB) Historically Contaminated
      Marine Sediment under Conditions Promoting Reductive Dechlorination.
AB  - The toxicity of polychlorinated biphenyls (PCB) can be efficiently reduced in
      contaminated marine sediments through the reductive dechlorination (RD) process
      lead by anaerobic organohalide bacteria. Although the process has been
      extensively investigated on PCB-spiked sediments, the knowledge on the identity
      and metabolic potential of PCB-dechlorinating microorganisms in real contaminated
      matrix is still limited. Aim of this study was to explore the composition and the
      dynamics of the microbial communities of the marine sediment collected from one
      of the largest Sites of National Interest (SIN) in Italy (Mar Piccolo, Taranto)
      under conditions promoting the PCBs RD. A long-term microcosm study revealed that
      autochthonous bacteria were able to sustain the PCB dechlorination at a high
      extent and the successive addition of an external fermentable organic substrate
      (lactate) caused the further depletion of the high-chlorinated PCBs (up to 70%).
      Next Generation Sequencing was used to describe the core microbiome of the marine
      sediment and to follow the changes caused by the treatments. OTUs affiliated to
      sulfur-oxidizing epsilon-proteobacteria, Sulfurovum, and Sulfurimonas, were
      predominant in the original sediment and increased up to 60% of total OTUs after
      lactate addition. Other OTUs detected in the sediment were affiliated to sulfate
      reducing (delta-proteobacteria) and to organohalide respiring bacteria within
      Chloroflexi phylum mainly belonging to Dehalococcoidia class. Among others,
      Dehalococcoides mccartyi was enriched during the treatments even though the
      screening of the specific reductive dehalogenase genes revealed the occurrence of
      undescribed strains, which deserve further investigations. Overall, this study
      highlighted the potential of members of Dehalococcoidia class in reducing the
      contamination level of the marine sediment from Mar Piccolo with relevant
      implications on the selection of sustainable bioremediation strategies to clean
      up the site.

PMID- 27708638
TI  - Rhamnolipid Biosurfactant against Fusarium verticillioides to Control Stalk and
      Ear Rot Disease of Maize.
AB  - Antifungal activity of rhamnolipids (RLs) has been widely studied against many
      plant pathogenic fungi, but not against Fusarium verticillioides, a major
      pathogen of maize (Zea mays L.). F. verticillioides causes stalk and ear rot of
      maize or asymptomatically colonizes the plant and ears resulting in moderate to
      heavy crop loss throughout the world. F. verticillioides produces fumonisin
      mycotoxins, reported carcinogens, which makes the contaminated ears unsuitable
      for consumption. In this study, the RL produced using glucose as sole carbon
      source was characterized by FTIR and LCMS analyses and its antifungal activity
      against F. verticillioides was evaluated in vitro on maize stalks and seeds.
      Further, the effect of RL on the mycelia of F. verticillioides was investigated
      by scanning electron microscopy which revealed visible damage to the mycelial
      structure as compared to control samples. In planta, treatment of maize seeds
      with a RL concentration of 50 mg l-1 resulted in improved biomass and fruiting
      compared to those of healthy control plants and complete suppression of
      characteristic disease symptoms and colonization of maize by F. verticillioides.
      The study highlights the potential of RLs to be used for an effective biocontrol
      strategy against colonization of maize plant by F. verticillioides.

PMID- 27708639
TI  - The Synergistic Effect of High Pressure CO2 and Nisin on Inactivation of Bacillus
      subtilis Spores in Aqueous Solutions.
AB  - The inactivation effects of high pressure CO2 + nisin (simultaneous treatment of
      HPCD and nisin, HPCD + nisin), HPCD->nisin (HPCD was followed by nisin), and
      nisin->HPCD (nisin was followed by HPCD) treatments on Bacillus subtilis spores
      in aqueous solutions were compared. The spores were treated by HPCD at 6.5 or 20
      MPa, 84-86 degrees C and 0-30 min, and the concentration of nisin was 0.02%.
      Treated spores were examined for the viability, the permeability of inner
      membrane (IM) using flow cytometry method and pyridine-2, 6-dicarboxylic acid
      (DPA) release, and structural damage by transmission electron microscopy. A
      synergistic effect of HPCD + nisin treatment on inactivation of the spores was
      found, and the inactivation efficiency of the spores was HPCD + nisin > HPCD
      >nisin or nisin->HPCD. Moreover, HPCD + nisin caused higher IM permeability and
      DPA release of the spores than HPCD. A possible action mode of nisin-enhanced
      inactivation of the spores was suggested as that HPCD firstly damaged the coat
      and cortex of spores, and nisin penetrated into and acted on the IM of spores,
      which increased the damage to the IM of spores, and resulted in higher
      inactivation of the spores.

PMID- 27708640
TI  - A Screening Method for the Isolation of Polyhydroxyalkanoate-Producing Purple Non
      sulfur Photosynthetic Bacteria from Natural Seawater.
AB  - Polyhydroxyalkanoates (PHAs) are a family of biopolyesters accumulated by a
      variety of microorganisms as carbon and energy storage under starvation
      conditions. We focused on marine purple non-sulfur photosynthetic bacteria as
      host microorganisms for PHA production and developed a method for their isolation
      from natural seawater. To identify novel PHA-producing marine purple non-sulfur
      photosynthetic bacteria, natural seawaters were cultured in nutrient-rich medium
      for purple non-sulfur photosynthetic bacteria, and twelve pink- or red-pigmented
      colonies were picked up. Gas chromatography mass spectrometry analysis revealed
      that four isolates synthesized PHA at levels ranging from 0.5 to 24.4 wt% of cell
      dry weight. The 16S ribosomal RNA sequence analysis revealed that one isolate
      (HM2) showed 100% identity to marine purple non-sulfur photosynthetic bacteria.
      In conclusion, we have demonstrated in this study that PHA-producing marine
      purple non-sulfur photosynthetic bacteria can be isolated from natural seawater
      under nutrient-rich conditions.

PMID- 27708641
TI  - Differences in the Composition of Archaeal Communities in Sediments from
      Contrasting Zones of Lake Taihu.
AB  - In shallow lakes, different primary producers might impact the physiochemical
      characteristics of the sediment and the associated microbial communities. Until
      now, little was known about the features of sediment Archaea and their variation
      across different primary producer-dominated ecosystems. Lake Taihu provides a
      suitable study area with cyanobacteria- and macrophyte-dominated zones co
      occurring in one ecosystem. The composition of the sediment archaeal community
      was assessed using 16S rRNA gene amplicon sequencing technology, based on which
      the potential variation with respect to the physiochemical characteristics of the
      sediment was analyzed. Euryarchaeota (30.19% of total archaeal sequences) and
      Bathyarchaeota (28.00%) were the two most abundant phyla, followed by
      Crenarchaeota (11.37%), Aigarchaeota (10.24%) and Thaumarchaeota (5.98%). The
      differences found in the composition of the archaeal communities between the two
      zones was significant (p = 0.005). Sediment from macrophyte-dominated zones had
      high TOC and TN content and an abundance of archaeal lineages potentially
      involved in the degradation of complex organic compounds, such as the order
      Thermoplasmatales. In the area dominated by Cyanobacteria, archaeal lineages
      related to sulfur metabolism, for example, Sulfolobales and Desulfurococcales,
      were significantly enriched. Among Bathyarchaeota, subgroups MCG-6 and MCG-15
      were significantly accumulated in the sediment of areas dominated by macrophytes
      whereas MCG-4 was consistently dominant in both type of sediments. The present
      study contributes to the knowledge of sediment archaeal communities with
      different primary producers and their possible biogeochemical functions in
      sediment habitats.

PMID- 27708642
TI  - HIV Latency-Reversing Agents Have Diverse Effects on Natural Killer Cell
      Function.
AB  - In an effort to clear persistent HIV infection and achieve a durable therapy-free
      remission of HIV disease, extensive pre-clinical studies and early pilot clinical
      trials are underway to develop and test agents that can reverse latent HIV
      infection and present viral antigen to the immune system for clearance. It is,
      therefore, critical to understand the impact of latency-reversing agents (LRAs)
      on the function of immune effectors needed to clear infected cells. We assessed
      the impact of LRAs on the function of natural killer (NK) cells, the main
      effector cells of the innate immune system. We studied the effects of three
      histone deacetylase inhibitors [SAHA or vorinostat (VOR), romidepsin, and
      panobinostat (PNB)] and two protein kinase C agonists [prostratin (PROST) and
      ingenol] on the antiviral activity, cytotoxicity, cytokine secretion, phenotype,
      and viability of primary NK cells. We found that ex vivo exposure to VOR had
      minimal impact on all parameters assessed, while PNB caused a decrease in NK cell
      viability, antiviral activity, and cytotoxicity. PROST caused non-specific NK
      cell activation and, interestingly, improved antiviral activity. Overall, we
      found that LRAs can alter the function and fate of NK cells, and these effects
      must be carefully considered as strategies are developed to clear persistent HIV
      infection.

PMID- 27708643
TI  - Differential Regulation of Self-reactive CD4+ T Cells in Cervical Lymph Nodes and
      Central Nervous System during Viral Encephalomyelitis.
AB  - Viral infections have long been implicated as triggers of autoimmune diseases,
      including multiple sclerosis (MS), a central nervous system (CNS) inflammatory
      demyelinating disorder. Epitope spreading, molecular mimicry, cryptic antigen,
      and bystander activation have been implicated as mechanisms responsible for
      activating self-reactive (SR) immune cells, ultimately leading to organ-specific
      autoimmune disease. Taking advantage of coronavirus JHM strain of mouse hepatitis
      virus (JHMV)-induced demyelination, this study demonstrates that the host also
      mounts counteractive measures to specifically limit expansion of endogenous SR T
      cells. In this model, immune-mediated demyelination is associated with induction
      of SR T cells after viral control. However, their decline during persisting
      infection, despite ongoing demyelination, suggests an active control mechanism.
      Antigen-specific IL-10-secreting CD4+ T cells (Tr1) and Foxp3+ regulatory T cells
      (Tregs), both known to control autoimmunity and induced following JHMV infection,
      were assessed for their relative in vivo suppressive function of SR T cells.
      Ablation of Foxp3+ Tregs in chronically infected DEREG mice significantly
      increased SR CD4+ T cells within cervical lymph nodes (CLN), albeit without
      affecting their numbers or activation within the CNS compared to controls. In
      contrast, infected IL-27 receptor deficient (IL-27R-/-) mice, characterized by a
      drastic reduction of Tr1 cells, revealed that SR CD4+ T cells in CLN remained
      unchanged but were specifically increased within the CNS. These results suggest
      that distinct Treg subsets limit SR T cells in the draining lymph nodes and CNS
      to maximize suppression of SR T-cell-mediated autoimmune pathology. The JHMV
      model is thus valuable to decipher tissue-specific mechanisms preventing
      autoimmunity.

PMID- 27708644
TI  - Comparative Analysis of Immune Activation Markers of CD8+ T Cells in Lymph Nodes
      of Different Origins in SIV-Infected Chinese Rhesus Macaques.
AB  - Altered T-cell homeostasis, such as expansion of CD8+ T cells to the secondary
      lymphatic compartments, has been suggested as a mechanism of HIV/simian
      immunodeficiency virus (SIV)-pathogenesis. However, the role of immune activation
      of CD8+ T cells in the CD4/CD8 turnover and viral replication in these tissues is
      not completely understood. In this study, we compared the expression of immune
      activation markers (CD69 and HLA-DR) on CD8+ T cells in the peripheral blood and
      lymph nodes (LNs) of SIV-infected/uninfected Chinese rhesus macaques. SIV
      infected macaques had significantly higher percentages of CD8+CD69+ and CD8+HLA
      DR+ T cells in all these anatomical compartments than uninfected macaques. LNs
      that located close to the gastrointestinal (GI) tract (colon, mesenteric, and
      iliac LNs) of SIV-infected macaques had profoundly lower numbers of CD4+ T cells,
      but no significant difference in expression of activation marker (CD8+CD69+ and
      CD8+HLA-DR+) as compared with the peripheral lymphatic tissues (axillary and
      inguinal LNs). The CD4/CD8 ratios were negatively correlated with the activation
      of CD8+ T cells in the overall LNs, with further associations with CD8+HLA-DR+ in
      GI LNs while CD8+CD69+ in peripheral LNs. These observations demonstrate that the
      increase of CD8+ T cell activation is a contributing factor for the decline of
      CD4/CD8 ratios in GI system.

PMID- 27708645
TI  - SONAR: A High-Throughput Pipeline for Inferring Antibody Ontogenies from
      Longitudinal Sequencing of B Cell Transcripts.
AB  - The rapid advance of massively parallel or next-generation sequencing
      technologies has made possible the characterization of B cell receptor
      repertoires in ever greater detail, and these developments have triggered a
      proliferation of software tools for processing and annotating these data. Of
      especial interest, however, is the capability to track the development of
      specific antibody lineages across time, which remains beyond the scope of most
      current programs. We have previously reported on the use of techniques such as
      inter- and intradonor analysis and CDR3 tracing to identify transcripts related
      to an antibody of interest. Here, we present Software for the Ontogenic aNalysis
      of Antibody Repertoires (SONAR), capable of automating both general repertoire
      analysis and specialized techniques for investigating specific lineages. SONAR
      annotates next-generation sequencing data, identifies transcripts in a lineage of
      interest, and tracks lineage development across multiple time points. SONAR also
      generates figures, such as identity-divergence plots and longitudinal
      phylogenetic "birthday" trees, and provides interfaces to other programs such as
      DNAML and BEAST. SONAR can be downloaded as a ready-to-run Docker image or
      manually installed on a local machine. In the latter case, it can also be
      configured to take advantage of a high-performance computing cluster for the most
      computationally intensive steps, if available. In summary, this software provides
      a useful new tool for the processing of large next-generation sequencing datasets
      and the ontogenic analysis of neutralizing antibody lineages. SONAR can be found
      at https://github.com/scharch/SONAR, and the Docker image can be obtained from
      https://hub.docker.com/r/scharch/sonar/.

PMID- 27708647
TI  - Cherry Valley Ducks Mitochondrial Antiviral-Signaling Protein-Mediated Signaling
      Pathway and Antiviral Activity Research.
AB  - Mitochondrial antiviral-signaling protein (MAVS), an adaptor protein of retinoic
      acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated signal pathway, is
      involved in innate immunity. In this study, Cherry Valley duck MAVS (duMAVS) was
      cloned from the spleen and analyzed. duMAVS was determined to have a caspase
      activation and recruitment domain at N-terminal, followed by a proline-rich
      domain and a transmembrane domain at C-terminal. Quantitative real-time PCR
      indicated that duMAVS was expressed in all tissues tested across a broad
      expression spectrum. The expression of duMAVS was significantly upregulated after
      infection with duck Tembusu virus (DTMUV). Overexpression of duMAVS could drive
      the activation of interferon (IFN)-beta, nuclear factor-kappaB, interferon
      regulatory factor 7, and many downstream factors (such as Mx, PKR, OAS, and IL-8)
      in duck embryo fibroblast cells. What is more, RNA interference further confirmed
      that duMAVS was an important adaptor for IFN-beta activation. The antiviral assay
      showed that duMAVS could suppress the various viral replications (DTMUV, novel
      reovirus, and duck plague virus) at early stages of infection. Overall, these
      results showed that the main signal pathway mediated by duMAVS and it had a broad
      spectrum antiviral ability. This research will be helpful to better understanding
      the innate immune system of ducks.

PMID- 27708646
TI  - NETosis in Cancer - Platelet-Neutrophil Crosstalk Promotes Tumor-Associated
      Pathology.
AB  - It has become increasingly clear that circulating immune cells in the body have a
      major impact on cancer development, progression, and outcome. The role of both
      platelets and neutrophils as independent regulators of various processes in
      cancer has been known for long, but it has quite recently emerged that the
      platelet-neutrophil interplay is yet a critical component to take into account
      during malignant disease. It was reported a few years ago that neutrophils in
      mice with cancer have increased propensity to form neutrophil extracellular traps
      (NETs) - web-like structures formed by externalized chromatin and secreted
      proteases. The initial finding describing this as a cell death-associated process
      has been followed by reports of additional mechanisms for NET formation
      (NETosis), and it has been shown that similar structures can be formed also
      without lysis and neutrophil cell death as a consequence. Furthermore, presence
      of NETs in humans with cancer has been verified in a few recent studies,
      indicating that tumor-induced NETosis is clinically relevant. Several reports
      have also described that NETs contribute to cancer-associated pathology, by
      promoting processes responsible for cancer-related death such as thrombosis,
      systemic inflammation, and relapse of the disease. This review summarizes current
      knowledge about NETosis in cancer, including the role of platelets as regulators
      of tumor-induced NETosis. It has been shown that platelets can serve as inducers
      of NETosis, and the platelet-neutrophil interface can therefore be an important
      issue to consider when designing therapies targeting cancer-associated pathology
      in the future.

PMID- 27708651
TI  - Editorial: Advances in Microalgae Biology and Sustainable Applications.

PMID- 27708648
TI  - Generation of Marker- and/or Backbone-Free Transgenic Wheat Plants via
      Agrobacterium-Mediated Transformation.
AB  - Horizontal transfer of antibiotic resistance genes to animals and vertical
      transfer of herbicide resistance genes to the weedy relatives are perceived as
      major biosafety concerns in genetically modified (GM) crops. In this study, five
      novel vectors which used gusA and bar as a reporter gene and a selection marker
      gene, respectively, were constructed based on the pCLEAN dual binary vector
      system. Among these vectors, 1G7B and 5G7B carried two T-DNAs located on two
      respective plasmids with 5G7B possessing an additional virGwt gene. 5LBTG154 and
      5TGTB154 carried two T-DNAs in the target plasmid with either one or double right
      borders, and 5BTG154 carried the selectable marker gene on the backbone outside
      of the T-DNA left border in the target plasmid. In addition, 5BTG154, 5LBTG154,
      and 5TGTB154 used pAL154 as a helper plasmid which contains Komari fragment to
      facilitate transformation. These five dual binary vector combinations were
      transformed into Agrobacterium strain AGL1 and used to transform durum wheat cv
      Stewart 63. Evaluation of the co-transformation efficiencies, the frequencies of
      marker-free transgenic plants, and integration of backbone sequences in the
      obtained transgenic lines indicated that two vectors (5G7B and 5TGTB154) were
      more efficient in generating marker-free transgenic wheat plants with no or
      minimal integration of backbone sequences in the wheat genome. The vector series
      developed in this study for generation of marker- and/or backbone-free transgenic
      wheat plants via Agrobacterium-mediated transformation will be useful to
      facilitate the creation of "clean" GM wheat containing only the foreign genes of
      agronomic importance.

PMID- 27708650
TI  - A Novel FC116/BC10 Mutation Distinctively Causes Alteration in the Expression of
      the Genes for Cell Wall Polymer Synthesis in Rice.
AB  - We report isolation and characterization of a fragile culm mutant fc116 that
      displays reduced mechanical strength caused by decreased cellulose content and
      altered cell wall structure in rice. Map-based cloning revealed that fc116 was a
      base substitution mutant (G to A) in a putative beta-1,6-N
      acetylglucosaminyltransferase (C2GnT) gene (LOC_Os05g07790, allelic to BC10).
      This mutation resulted in one amino acid missing within a newly-identified
      protein motif "R, RXG, RA." The FC116/BC10 gene was lowly but ubiquitously
      expressed in the all tissues examined across the whole life cycle of rice, and
      slightly down-regulated during secondary growth. This mutant also exhibited a
      significant increase in the content of hemicelluloses and lignins, as well as the
      content of pentoses (xylose and arabinose). But the content of hexoses (glucose,
      mannose, and galactose) was decreased in both cellulosic and non-cellulosic
      (pectins and hemicelluloses) fractions of the mutant. Transcriptomic analysis
      indicated that the typical genes in the fc116 mutant were up-regulated
      corresponding to xylan biosynthesis, as well as lignin biosynthesis including p
      hydroxyphenyl (H), syringyl (S), and guaiacyl (G). Our results indicate that
      FC116 has universal function in regulation of the cell wall polymers in rice.

PMID- 27708649
TI  - Gene Overexpression Resources in Cereals for Functional Genomics and Discovery of
      Useful Genes.
AB  - Identification and elucidation of functions of plant genes is valuable for both
      basic and applied research. In addition to natural variation in model plants,
      numerous loss-of-function resources have been produced by mutagenesis with
      chemicals, irradiation, or insertions of transposable elements or T-DNA. However,
      we may be unable to observe loss-of-function phenotypes for genes with
      functionally redundant homologs and for those essential for growth and
      development. To offset such disadvantages, gain-of-function transgenic resources
      have been exploited. Activation-tagged lines have been generated using obligatory
      overexpression of endogenous genes by random insertion of an enhancer. Recent
      progress in DNA sequencing technology and bioinformatics has enabled the
      preparation of genomewide collections of full-length cDNAs (fl-cDNAs) in some
      model species. Using the fl-cDNA clones, a novel gain-of-function strategy, Fl
      cDNA OvereXpressor gene (FOX)-hunting system, has been developed. A mutant
      phenotype in a FOX line can be directly attributed to the overexpressed fl-cDNA.
      Investigating a large population of FOX lines could reveal important genes
      conferring favorable phenotypes for crop breeding. Alternatively, a unique loss
      of-function approach Chimeric REpressor gene Silencing Technology (CRES-T) has
      been developed. In CRES-T, overexpression of a chimeric repressor, composed of
      the coding sequence of a transcription factor (TF) and short peptide designated
      as the repression domain, could interfere with the action of endogenous TF in
      plants. Although plant TFs usually consist of gene families, CRES-T is effective,
      in principle, even for the TFs with functional redundancy. In this review, we
      focus on the current status of the gene-overexpression strategies and resources
      for identifying and elucidating novel functions of cereal genes. We discuss the
      potential of these research tools for identifying useful genes and phenotypes for
      application in crop breeding.

PMID- 27708652
TI  - Melatonin-Producing Endophytic Bacteria from Grapevine Roots Promote the Abiotic
      Stress-Induced Production of Endogenous Melatonin in Their Hosts.
AB  - Endophytes form symbiotic relationships with plants and constitute an important
      source of phytohormones and bioactive secondary metabolites for their hosts. To
      date, most studies of endophytes have focused on the influence of these
      microorganisms on plant growth and physiology and their role in plant defenses
      against biotic and abiotic stressors; however, to the best of our knowledge, the
      ability of endophytes to produce melatonin has not been reported. In the present
      study, we isolated and identified root-dwelling bacteria from three grapevine
      varieties and found that, when cultured under laboratory conditions, some of the
      bacteria strains secreted melatonin and tryptophan-ethyl ester. The endophytic
      bacterium Bacillus amyloliquefaciens SB-9 exhibited the highest level of in vitro
      melatonin secretion and also produced three intermediates of the melatonin
      biosynthesis pathway: 5-hydroxytryptophan, serotonin, and N-acetylserotonin.
      After B. amyloliquefaciens SB-9 colonization, the plantlets exhibited increased
      plant growth. Additionally, we found that, in grapevine plantlets exposed to salt
      or drought stress, colonization by B. amyloliquefaciens SB-9 increased the
      upregulation of melatonin synthesis, as well as that of its intermediates, but
      reduced the upregulation of grapevine tryptophan decarboxylase genes (VvTDCs) and
      a serotonin N-acetyltransferase gene (VvSNAT) transcription, when compared to the
      un-inoculated control. Colonization by B. amyloliquefaciens SB-9 was also able to
      counteract the adverse effects of salt- and drought-induced stress by reducing
      the production of malondialdehyde and reactive oxygen species (H2O2 and O2-) in
      roots. Therefore, our findings demonstrate the occurrence of melatonin
      biosynthesis in endophytic bacteria and provide evidence for a novel form of
      communication between beneficial endophytes and host plants via melatonin.

PMID- 27708654
TI  - The 4-Dimensional Plant: Effects of Wind-Induced Canopy Movement on Light
      Fluctuations and Photosynthesis.
AB  - Physical perturbation of a plant canopy brought about by wind is a ubiquitous
      phenomenon and yet its biological importance has often been overlooked. This is
      partly due to the complexity of the issue at hand: wind-induced movement (or
      mechanical excitation) is a stochastic process which is difficult to measure and
      quantify; plant motion is dependent upon canopy architectural features which,
      until recently, were difficult to accurately represent and model in 3-dimensions;
      light patterning throughout a canopy is difficult to compute at high-resolutions,
      especially when confounded by other environmental variables. Recent studies have
      reinforced the expectation that canopy architecture is a strong determinant of
      productivity and yield; however, links between the architectural properties of
      the plant and its mechanical properties, particularly its response to wind, are
      relatively unknown. As a result, biologically relevant data relating canopy
      architecture, light- dynamics, and short-scale photosynthetic responses in the
      canopy setting are scarce. Here, we hypothesize that wind-induced movement will
      have large consequences for the photosynthetic productivity of our crops due to
      its influence on light patterning. To address this issue, in this study we
      combined high resolution 3D reconstructions of a plant canopy with a simple
      representation of canopy perturbation as a result of wind using solid body
      rotation in order to explore the potential effects on light patterning,
      interception, and photosynthetic productivity. We looked at two different
      scenarios: firstly a constant distortion where a rice canopy was subject to a
      permanent distortion throughout the whole day; and secondly, a dynamic
      distortion, where the canopy was distorted in incremental steps between two
      extremes at set time points in the day. We find that mechanical canopy excitation
      substantially alters light dynamics; light distribution and modeled canopy carbon
      gain. We then discuss methods required for accurate modeling of mechanical canopy
      excitation (here coined the 4-dimensional plant) and some associated biological
      and applied implications of such techniques. We hypothesize that biomechanical
      plant properties are a specific adaptation to achieve wind-induced photosynthetic
      enhancement and we outline how traits facilitating canopy excitation could be
      used as a route for improving crop yield.

PMID- 27708653
TI  - Transporters Involved in Root Nitrate Uptake and Sensing by Arabidopsis.
AB  - Most plants use nitrate (NO3-) as their major nitrogen (N) source. The NO3-
      uptake capacity of a plant is determined by three interdependent factors that are
      sensitive to NO3- availability: (i) the functional properties of the transporters
      in roots that contribute to the acquisition of NO3- from the external medium,
      (ii) the density of functional transporters at the plasma membrane of root cells,
      and (iii) the surface and architecture of the root system. The identification of
      factors that regulate the NO3--sensing systems is important for both fundamental
      and applied science, because these factors control the capacity of plants to use
      the available NO3-, a process known as the "nitrate use efficiency." The
      molecular component of the transporters involved in uptake and sensing mechanism
      in Arabidopsis roots are presented and their relative contribution discussed.

PMID- 27708655
TI  - Proteomic Analysis Reveals Different Involvement of Embryo and Endosperm Proteins
      during Aging of Yliangyou 2 Hybrid Rice Seeds.
AB  - Seed aging is a process that results in a delayed germination, a decreased
      germination percentage, and finally a total loss of seed viability. However, the
      mechanism of seed aging is poorly understood. In the present study, Yliangyou 2
      hybrid rice (Oryza sativa L.) seeds were artificially aged at 100% relative
      humidity and 40 degrees C, and the effect of artificial aging on germination,
      germination time course and the change in protein profiles of embryo and
      endosperm was studied to understand the molecular mechanism behind seed aging.
      With an increasing duration of artificial aging, the germination percentage and
      germination rate of hybrid rice seeds decreased. By comparing the protein
      profiles from the seeds aged for 0, 10 and 25 days, a total of 91 and 100 protein
      spots were found to show a significant change of more than 2-fold (P < 0.05) in
      abundance, and 71 and 79 protein spots were identified, in embryos and
      endosperms, respectively. The great majority of these proteins increased in
      abundance in embryos (95%) and decreased in abundance in endosperms (99%). In
      embryos, most of the identified proteins were associated with energy (30%), with
      cell defense and rescue (28%), and with storage protein (18%). In endosperms,
      most of the identified proteins were involved in metabolism (37%), in energy
      (27%), and in protein synthesis and destination (11%). The most marked change was
      the increased abundance of many glycolytic enzymes together with the two
      fermentation enzymes pyruvate decarboxylase and alcohol dehydrogenase in the
      embryos during aging. We hypothesize that the decreased viability of hybrid rice
      seeds during artificial aging is caused by the development of hypoxic conditions
      in the embryos followed by ethanol accumulation.

PMID- 27708656
TI  - Transcriptome Analysis of Stem and Globally Comparison with Other Tissues in
      Brassica napus.
AB  - Brassica napus is one of the most important oilseed crops in the world. However,
      there is currently no enough stem transcriptome information and comparative
      transcriptome analysis of different tissues, which impedes further functional
      genomics research on B. napus. In this study, the stem transcriptome of B. napus
      was characterized by RNA-seq technology. Approximately 13.4 Gb high-quality clean
      reads with an average length of 100 bp were generated and used for comparative
      transcriptome analysis with the existing transcriptome sequencing data of roots,
      leaves, flower buds, and immature embryos of B. napus. All the transcripts were
      annotated against GO and KEGG databases. The common genes in five tissues,
      differentially expressed genes (DEGs) of the common genes between stems and other
      tissues, and tissue-specific genes were detected, and the main biochemical
      activities and pathways implying the common genes, DEGs and tissue-specific genes
      were investigated. Accordingly, the common transcription factors (TFs) in the
      five tissues and tissue-specific TFs were identified, and a TFs-based regulation
      network between TFs and the target genes involved in 'Phenylpropanoid
      biosynthesis' pathway were constructed to show several important TFs and key
      nodes in the regulation process. Collectively, this study not only provided an
      available stem transcriptome resource in B. napus, but also revealed valuable
      comparative transcriptome information of five tissues of B. napus for future
      investigation on specific processes, functions and pathways.

PMID- 27708657
TI  - Monte Carlo Modeling of Photon Propagation Reveals Highly Scattering Coral
      Tissue.
AB  - Corals are very efficient at using solar radiation, with photosynthetic quantum
      efficiencies approaching theoretical limits. Here, we investigated potential
      mechanisms underlying such outstanding photosynthetic performance through
      extracting inherent optical properties of the living coral tissue and skeleton in
      a massive faviid coral. Using Monte Carlo simulations developed for medical
      tissue optics it is shown that for the investigated faviid coral, the coral
      tissue was a strongly light scattering matrix with a reduced scattering
      coefficient of MUs' = 10 cm-1 (at 636 nm). In contrast, the scattering
      coefficient of the coral skeleton was MUs' = 3.4 cm-1, which facilitated the
      efficient propagation of light to otherwise shaded coral tissue layers, thus
      supporting photosynthesis in lower tissues. Our study provides a quantification
      of coral tissue optical properties in a massive faviid coral and suggests a novel
      light harvesting strategy, where tissue and skeletal optics act in concert to
      optimize the illumination of the photosynthesizing algal symbionts embedded
      within the living coral tissue.

PMID- 27708658
TI  - Carotenoid Derivates in Achiote (Bixa orellana) Seeds: Synthesis and Health
      Promoting Properties.
AB  - Bixa orellana (family Bixaceae) is a neotropical fast growing perennial tree of
      great agro-industrial value because its seeds have a high carotenoid content,
      mainly bixin. It has been used since pre-colonial times as a culinary colorant
      and spice, and for healing purposes. It is currently used as a natural pigment in
      the food, in pharmaceutical, and cosmetic industries, and it is commercially
      known as annatto. Recently, several studies have addressed the biological and
      medical properties of this natural pigment, both as potential source of new drugs
      or because its ingestion as a condiment or diet supplement may protect against
      several diseases. The most documented properties are anti-oxidative; but its anti
      cancer, hypoglucemic, antibiotic and anti-inflammatory properties are also being
      studied. Bixin's pathway elucidation and its regulation mechanisms are critical
      to improve the produce of this important carotenoid. Even though the bixin
      pathway has been established, the regulation of the genes involved in bixin
      production remains largely unknown. Our laboratory recently published B.
      orellana's transcriptome and we have identified most of its MEP (methyl-D
      erythritol 4-phosphate) and carotenoid pathway genes. Annatto is a potential
      source of new drugs and can be a valuable nutraceutical supplement. However, its
      nutritional and healing properties require further study.

PMID- 27708660
TI  - The Effect of Orobanche crenata Infection Severity in Faba Bean, Field Pea, and
      Grass Pea Productivity.
AB  - Broomrape weeds (Orobanche and Phelipanche spp.) are root holoparasites that feed
      off a wide range of important crops. Among them, Orobanche crenata attacks
      legumes complicating their inclusion in cropping systems along the Mediterranean
      area and West Asia. The detrimental effect of broomrape parasitism in crop yield
      can reach up to 100% depending on infection severity and the broomrape-crop
      association. This work provides field data of the consequences of O. crenata
      infection severity in three legume crops, i.e., faba bean, field pea, and grass
      pea. Regression functions modeled productivity losses and revealed trends in dry
      matter allocation in relation to infection severity. The host species
      differentially limits parasitic sink strength indicating different levels of
      broomrape tolerance at equivalent infection severities. Reductions in host
      aboveground biomass were observed starting at low infection severity and half
      maximal inhibitory performance was predicted as 4.5, 8.2, and 1.5 parasites per
      faba bean, field pea, and grass pea plant, respectively. Reductions in host
      biomass occurred in both vegetative and reproductive organs, the latter resulting
      more affected. The increase of resources allocated within the parasite was
      concomitant to reduction of host seed yield indicating that parasite growth and
      host reproduction compete directly for resources within a host plant. However,
      the parasitic sink activity does not fully explain the total host biomass
      reduction because combined biomass of host-parasite complex was lower than the
      biomass of uninfected plants. In grass pea, the seed yield was negligible at
      severities higher than four parasites per plant. In contrast, faba bean and field
      pea sustained low but significant seed production at the highest infection
      severity. Data on seed yield and seed number indicated that the sensitivity of
      field pea to O. crenata limited the production of grain yield by reducing seed
      number but maintaining seed size. In contrast, the size of individual parasites
      was not genetically determined but dependent on the host species and resource
      availability as a consequence of competition between parasites at increasing
      infection severities.

PMID- 27708659
TI  - Genetic Diversity, Rather than Cultivar Type, Determines Relative Grain Cd
      Accumulation in Hybrid Rice.
AB  - Cadmium (Cd) is a toxic element, and rice is known to be a leading source of
      dietary Cd for people who consume rice as their main caloric resource. Hybrid
      rice has dominated rice production in southern China and has been adopted
      worldwide. The characteristics of high yield heterosis of rice hybrids makes the
      public think intuitively that the hybrid rice accumulates more Cd in grain than
      do inbred cultivars. A detailed understanding of the genetic basis of grain Cd
      accumulation in hybrids and developing Cd-safe rice are one of the top priorities
      for hybrid rice breeders at present. In this study, we investigated genetic
      diversity and grain Cd levels in 617 elite rice hybrids collected from the middle
      and lower Yangtze River Valley in China and 68 inbred cultivars from around the
      world. We found that there are large variations in grain Cd accumulation in both
      the hybrids and their inbred counterparts. However, we found grain Cd levels in
      the rice hybrids to be similar to the levels in indica rice inbreds, suggesting
      that the hybrids do not accumulate more Cd than do the inbred rice cultivars.
      Further analysis revealed that the high heritability of Cd accumulation in the
      grain and the single indica population structure increases the risk of Cd over
      accumulation in hybrid rice. The genetic effects of Cd-related QTLs, which have
      been identified in related Cd-QTL mapping studies, were also determined in the
      hybrid rice population. Four QTLs were identified as being associated with the
      variation in grain Cd levels; three of these loci exhibited obvious indica
      japonica differentiations. Our study will provide a better understanding of grain
      Cd accumulations in hybrid rice, and pave the way toward effective breeding for
      high-yielding, low grain-Cd hybrids in the future.

PMID- 27708661
TI  - Moderate Genetic Diversity and Genetic Differentiation in the Relict Tree
      Liquidambar formosana Hance Revealed by Genic Simple Sequence Repeat Markers.
AB  - Chinese sweetgum (Liquidambar formosana) is a relatively fast-growing ecological
      pioneer species. It is widely used for multiple purposes. To assess the genetic
      diversity and genetic differentiation of the species, genic SSR markers were
      mined from transcriptome data for subsequent analysis of the genetic diversity
      and population structure of natural populations. A total of 10645 potential genic
      SSR loci were identified in 80482 unigenes. The average frequency was one SSR per
      5.12 kb, and the dinucleotide unit was the most abundant motif. A total of 67
      alleles were found, with a mean of 6.091 alleles per locus and a mean
      polymorphism information content of 0.390. Moreover, the species exhibited a
      relatively moderate level of genetic diversity (He = 0.399), with the highest was
      found in population XY (He = 0.469). At the regional level, the southwestern
      region displayed the highest genetic diversity (He = 0.435) and the largest
      number of private alleles (n = 5), which indicated that the Southwestern region
      may be the diversity hot spot of L. formosana. The AMOVA results showed that
      variation within populations (94.02%) was significantly higher than among
      populations (5.98%), which was in agreement with the coefficient of genetic
      differentiation (Fst = 0.076). According to the UPGMA analysis and principal
      coordinate analysis and confirmed by the assignment test, 25 populations could be
      divided into three groups, and there were different degrees of introgression
      among populations. No correlation was found between genetic distance and
      geographic distance (P > 0.05). These results provided further evidence that
      geographic isolation was not the primary factor leading to the moderate genetic
      differentiation of L. formosana. As most of the genetic diversity of L. formosana
      exists among individuals within a population, individual plant selection would be
      an effective way to use natural variation in genetic improvement programs. This
      would be helpful to not only protect the genetic resources but also attain
      effective management and exploit genetic resources.

PMID- 27708662
TI  - Comparative Analysis of miRNAs and Their Target Transcripts between a Spontaneous
      Late-Ripening Sweet Orange Mutant and Its Wild-Type Using Small RNA and Degradome
      Sequencing.
AB  - Fruit ripening in citrus is not well-understood at the molecular level. Knowledge
      of the regulatory mechanism of citrus fruit ripening at the post-transcriptional
      level in particular is lacking. Here, we comparatively analyzed the miRNAs and
      their target genes in a spontaneous late-ripening mutant, "Fengwan" sweet orange
      (MT) (Citrus sinensis L. Osbeck), and its wild-type counterpart ("Fengjie 72-1,"
      WT). Using high-throughput sequencing of small RNAs and RNA degradome tags, we
      identified 107 known and 21 novel miRNAs, as well as 225 target genes. A total of
      24 miRNAs (16 known miRNAs and 8 novel miRNAs) were shown to be differentially
      expressed between MT and WT. The expression pattern of several key miRNAs and
      their target genes during citrus fruit development and ripening stages was
      examined. Csi-miR156k, csi-miR159, and csi-miR166d suppressed specific
      transcription factors (GAMYBs, SPLs, and ATHBs) that are supposed to be important
      regulators involved in citrus fruit development and ripening. In the present
      study, miRNA-mediated silencing of target genes was found under complicated and
      sensitive regulation in citrus fruit. The identification of miRNAs and their
      target genes provide new clues for future investigation of mechanisms that
      regulate citrus fruit ripening.

PMID- 27708663
TI  - Invasive Chloroplast Population Genetics of Mikania micrantha in China: No Local
      Adaptation and Negative Correlation between Diversity and Geographic Distance.
AB  - Two fundamental questions on how invasive species are able to rapidly colonize
      novel habitat have emerged. One asks whether a negative correlation exists
      between the genetic diversity of invasive populations and their geographic
      distance from the origin of introduction. The other is whether selection on the
      chloroplast genome is important driver of adaptation to novel soil environments.
      Here, we addressed these questions in a study of the noxious invasive weed,
      Mikania micrantha, which has rapidly expanded in to southern China after being
      introduced to Hong Kong in 1884. Seven chloroplast simple sequence repeats
      (cpSSRs) were used to investigate population genetics in 28 populations of M.
      micrantha, which produced 39 loci. The soil compositions for these populations,
      including Mg abundance, were measured. The results showed that M. micrantha
      possessed relatively high cpSSR variation and differentiation among populations.
      Multiple diversity indices were quantified, and none was significantly correlated
      with distance from the origin of introduction. No evidence for "isolation by
      distance," significant spatial structure, bottlenecks, nor linkage disequilibrium
      was detected. We also were unable to identify loci on the chloroplast genome that
      exhibited patterns of differentiation that would suggest adaptive evolution in
      response to soil attributes. Soil Mg had only a genome-wide effect instead of
      being a selective factor, which highlighted the association between Mg and the
      successful invasion. This study characterizes the role of the chloroplast genome
      of M. micrantha during its recent invasion of southern China.

PMID- 27708665
TI  - Time Hierarchies and Model Reduction in Canonical Non-linear Models.
AB  - The time-scale hierarchies of a very general class of models in differential
      equations is analyzed. Classical methods for model reduction and time-scale
      analysis have been adapted to this formalism and a complementary method is
      proposed. A unified theoretical treatment shows how the structure of the system
      can be much better understood by inspection of two sets of singular values: one
      related to the stoichiometric structure of the system and another to its
      kinetics. The methods are exemplified first through a toy model, then a large
      synthetic network and finally with numeric simulations of three classical
      benchmark models of real biological systems.

PMID- 27708664
TI  - Single-Cell Transcriptomics Bioinformatics and Computational Challenges.
AB  - The emerging single-cell RNA-Seq (scRNA-Seq) technology holds the promise to
      revolutionize our understanding of diseases and associated biological processes
      at an unprecedented resolution. It opens the door to reveal intercellular
      heterogeneity and has been employed to a variety of applications, ranging from
      characterizing cancer cells subpopulations to elucidating tumor resistance
      mechanisms. Parallel to improving experimental protocols to deal with
      technological issues, deriving new analytical methods to interpret the complexity
      in scRNA-Seq data is just as challenging. Here, we review current state-of-the
      art bioinformatics tools and methods for scRNA-Seq analysis, as well as
      addressing some critical analytical challenges that the field faces.

PMID- 27708666
TI  - Co-expression Pattern Analysis of miR-17-92 Target Genes in Chronic Myelogenous
      Leukemia.
AB  - MicroRNAs (miRNAs) are post-transcriptional regulators that regulate gene
      expression by binding to the 3' untranslated region of target mRNAs. Mature
      miRNAs transcribed from the miR-17-92 cluster have an oncogenic activity, which
      are overexpressed in chronic-phase chronic myelogenous leukemia (CML) patients
      compared with normal individuals. Besides, the tyrosine kinase activity of BCR
      ABL oncoprotein from the Philadelphia chromosome in CML can affect this miRNA
      cluster. Genes with similar mRNA expression profiles are likely to be regulated
      by the same regulators. We hypothesize that target genes regulated by the same
      miRNA are co-expressed. In this study, we aim to explore the difference in the co
      expression patterns of those genes potentially regulated by miR-17-92 cluster
      between the normal and the CML groups. We applied a statistical method for gene
      pair classification by identifying a disease-specific cutoff point that
      classified the co-expressed gene pairs into strong and weak co-expression
      classes. The method effectively identified the differences in the co-expression
      patterns from the overall structure. Functional annotation for co-expressed gene
      pairs showed that genes involved in the metabolism processes were more likely to
      be co-expressed in the normal group compared to the CML group. Our method can
      identify the co-expression pattern difference from the overall structure between
      two different distributions using the distribution-based statistical method.
      Functional annotation further provides the biological support. The co-expression
      pattern in the normal group is regarded as the inter-gene linkages, which
      represents the healthy pathological balance. Dysregulation of metabolism may be
      related to CML pathology. Our findings will provide useful information for
      investigating the novel CML mechanism and treatment.

PMID- 27708668
TI  - Erratum: The Regulation of DNA Damage Tolerance by Ubiquitin and Ubiquitin-Like
      Modifiers.
AB  - [This corrects the article on p. 105 in vol. 7, PMID: 27379156.].

PMID- 27708670
TI  - Pharmacy practice research produces findings that inform how pharmacists
      contribute to optimal drug therapy outcomes for Canadians.

PMID- 27708669
TI  - Genetic susceptibility to allergic bronchopulmonary aspergillosis in asthma: a
      genetic association study.
AB  - BACKGROUND: In patients with asthma, the fungus Aspergillus fumigatus can cause
      allergic bronchopulmonary aspergillosis (ABPA). Familial ABPA is reported, and
      some genetic factors have been associated with the disease, however, these are
      small studies (n <= 38) and do not explain all cases of ABPA. METHODS: We
      analysed SNPs in 95 ABPA patients, comparing frequencies to 152 atopic asthmatic
      and 279 healthy controls. Twenty two genes were selected from literature, and 195
      tagging SNPs were analysed for genetic association with ABPA using logistic
      regression corrected for multiple testing. We also analysed monocyte-derived
      macrophage gene expression before and during co-culture with A. fumigatus.
      RESULTS: Seventeen ABPA-associated SNPs (ABPA v Atopic asthma) were identified.
      Three remained significant after correction for multiple testing; IL13 rs20541,
      IL4R rs3024656, TLR3 rs1879026. We also identified minor differences in
      macrophage gene expression responses in the ABPA group compared to the control
      groups. CONCLUSIONS: Multiple SNPs are now associated with ABPA. Some are novel
      associations. These associations implicate cytokine pathways and receptors in the
      aberrant response to A. fumigatus and susceptibility to ABPA, providing insights
      into the pathogenesis of ABPA and/or its complications. We hope these results
      will lead to increased understanding and improved treatment and diagnostics for
      ABPA.

PMID- 27708671
TI  - Pharmacists without Borders Canada: An update.

PMID- 27708667
TI  - Admixture Mapping of African-American Women in the AMBER Consortium Identifies
      New Loci for Breast Cancer and Estrogen-Receptor Subtypes.
AB  - Recent genetic admixture coupled with striking differences in incidence of
      estrogen receptor (ER) breast cancer subtypes, as well as severity, between women
      of African and European ancestry, provides an excellent rationale for performing
      admixture mapping in African American women with breast cancer risk. We performed
      the largest breast cancer admixture mapping study with in African American women
      to identify novel genomic regions associated with the disease. We conducted a
      genome-wide admixture scan using 2,624 autosomal ancestry informative markers
      (AIMs) in 3,629 breast cancer cases (including 1,968 ER-positive, 1093 ER
      negative, and 601 triple-negative) and 4,658 controls from the African American
      Breast Cancer Epidemiology and Risk (AMBER) Consortium, a collaborative study of
      four large geographically different epidemiological studies of breast cancer in
      African American women. We used an independent case-control study to test for SNP
      association in regions with genome-wide significant admixture signals. We found
      two novel genome-wide significant regions of excess African ancestry, 4p16.1 and
      17q25.1, associated with ER-positive breast cancer. Two regions known to harbor
      breast cancer variants, 10q26 and 11q13, were also identified with excess of
      African ancestry. Fine-mapping of the identified genome-wide significant regions
      suggests the presence of significant genetic associations with ER-positive breast
      cancer in 4p16.1 and 11q13. In summary, we identified three novel genomic regions
      associated with breast cancer risk by ER status, suggesting that additional
      previously unidentified variants may contribute to the racial differences in
      breast cancer risk in the African American population.

PMID- 27708672
TI  - Inhaler assessment in COPD patients: A primer for pharmacists.

PMID- 27708673
TI  - The community pharmacist's role in cancer screening and prevention.
AB  - As the Canadian population continues to age, the incidence of cancer is on the
      rise. To help alleviate the burden malignancy imposes on our health care system,
      a shift toward early cancer detection is necessary. Pharmacists are well
      positioned and willing to assume a more active role in cancer surveillance.
      Patients are receptive to pharmacist involvement and seem to prefer a convenient
      community pharmacy-based location for screening programs. The community
      pharmacist's current and potential role in cancer screening and prevention is
      summarized in this article. A review of screening recommendations and a
      discussion of opportunities will hopefully inspire pharmacists to consider
      incorporating malignancy screening initiatives into their practice.

PMID- 27708674
TI  - A randomized trial of a community-based approach to dyslipidemia management:
      Pharmacist prescribing to achieve cholesterol targets (RxACT Study).
AB  - BACKGROUND: Dyslipidemia is an important risk factor for cardiovascular disease
      but is suboptimally managed. Pharmacists are accessible primary care
      professionals and with expanded scopes of practice (including prescribing), could
      identify and manage patients with dyslipidemia. We sought to evaluate the effect
      of pharmacist prescribing of dyslipidemia medications on the proportion of
      participants achieving target LDL-cholesterol (LDL-c) levels. METHODS: We
      conducted a randomized controlled trial in 14 community pharmacies in Alberta,
      Canada. We enrolled adults with uncontrolled dyslipidemia as defined by the 2009
      Canadian Dyslipidemia Guidelines. Intervention was pharmacist-directed
      dyslipidemia care, including assessment of cardiovascular risk, review of LDL-c,
      prescribing of medications, health behaviour interventions and follow-up every 6
      weeks for 6 months. Usual care patients received their lipid results and a
      pamphlet on cardiovascular disease and usual care from their physician and
      pharmacist. Primary outcome was the proportion of participants achieving their
      target LDL-c (<2 mmol/L or >=50% reduction) at 6 months between groups. RESULTS:
      We enrolled 99 patients with a mean (SD) age of 63 (13) years, 49% male and
      baseline LDL-c of 3.37 mmol/L (0.98). Proportion of patients achieving LDL-c
      target was 43% intervention versus 18% control (p = 0.007). Adjusted odds of
      achieving target LDL-c were 3.3 times higher for the intervention group (p =
      0.031), who also achieved greater reduction in LDL-c (1.12 mmol/L, SE = 0.112)
      versus control (0.42 mmol/L, SE = 0.109), for an adjusted mean difference of
      0.546 mmol/L (SE = 0.157), p < 0.001. CONCLUSION: Pharmacist prescribing resulted
      in >3-fold more patients achieving target LDL-c levels. This could have major
      public health implications.

PMID- 27708675
TI  - Uptake of the MedsCheck annual medication review service in Ontario community
      pharmacies between 2007 and 2013.
AB  - BACKGROUND: MedsCheck Annual (MCA) is an Ontario government-funded medication
      review service for individuals taking 3 or more prescription medications for
      chronic conditions. METHODS: This cohort study analyzed linked administrative
      claims data from April 1, 2007, to March 31, 2013. Trends in MCA claims and
      recipient characteristics were examined. RESULTS: A total of 1,498,440 Ontarians
      (55% seniors, 55% female) received an MCA. One-third (36%) had 2 or more MCAs
      within 6 years. Service provision increased over time, with a sharper increase
      from 2010 onward. Almost half of Ontario pharmacies made at least 1 MCA claim in
      the first month of the program. Hypertension, respiratory disease, diabetes,
      psychiatric conditions and arthritis were common comorbidities. Recipients older
      than 65 years were most commonly dispensed an antihypertensive and/or
      antihyperlipidemic drug in the prior year and received an average of 11 unique
      prescription medications. Thirty-eight percent of recipients visited an emergency
      department or were hospitalized in the year prior to their first MCA. DISCUSSION:
      Over the first 6 years of the program, approximately 1 in 9 Ontarians received an
      MCA. There was rapid and widespread uptake of the service. Common chronic
      conditions were well represented among MCA recipients. Older MCA recipients had
      less emergency department use compared with population-based estimates.
      CONCLUSIONS: Medication reviews increased over time; however, the number of
      persons receiving the service more than once was low. Service delivery was
      generally consistent with program eligibility; however, there are some findings
      possibly consistent with delivery to less complex patients.

PMID- 27708676
TI  - Quit rates at 6 months in a pharmacist-led smoking cessation service in Malaysia.
AB  - BACKGROUND: Smoking cessation clinics have been established in Malaysia since
      2004, but wide variations in success rates have been observed. This study aimed
      to evaluate the proposed pharmacist-led Integrated Quit Smoking Service (IQSS) in
      Sabah, Malaysia, and identify factors associated with successful smoking
      cessation. METHODS: Data from 176 participants were collected from one of the
      quit-smoking centres in Sabah, Malaysia. Pharmacists, doctors and nurses were
      involved throughout the study. Any health care provider can refer patients for
      smoking cessation, and free pharmacotherapy and counselling was provided during
      the cessation period for up to 3 months. Information on demographic
      characteristics, smoking behaviours, follow-up and pharmacotherapy were
      collected. The main outcome measure was the abstinence from smoking, which was
      verified through carbon monoxide in expired air during the 6-month follow-up.
      RESULTS: A 42.6% success rate was achieved in IQSS. Smoking behaviour such as
      lower cigarette intake and lower Fagerstrom score were identified as factors
      associated with success. On top of that, a longer duration of follow-up and more
      frequent visits were significantly associated with success in quitting smoking.
      CONCLUSION: Collaboration among health care practitioners should be the main
      focus, and we need a combination of proven effective modalities in order to
      create an ideal smoking cessation module.

PMID- 27708677
TI  - Pharmacoeconomic comparison of aripiprazole once-monthly and paliperidone
      palmitate from a head-to-head clinical trial in schizophrenia: a US analysis.
AB  - Schizophrenia presents a substantial clinical and economic burden to the health
      care system. In QUAlity of LIfe with AbiliFY Maintena (QUALIFY), a randomized
      head-to-head study of aripiprazole once-monthly 400 mg (AOM 400) compared with
      paliperidone palmitate (PP; 78-234 mg/mo), AOM 400 demonstrated greater
      improvement in health-related quality of life and functioning in patients with
      stable schizophrenia. The present analysis used health economics assessment data
      collected during the QUALIFY study to determine the direct medical and pharmacy
      costs and the cost-effectiveness associated with each treatment over 6 months.
      Compared with those receiving PP, patients receiving AOM 400 incurred
      significantly lower direct total costs ($8908+/-186 vs $9675+/-190, p=0.005) and
      treatment costs ($7967+/-113 vs $8706+/-116, p<0.001). Effectiveness results in
      the subset of patients included in the cost analyses were similar to the overall
      population: mean (95% CI) improvement in Heinrichs-Carpenter Quality of Life
      Scale total score was greater with AOM 400 (5.97 [3.87; 8.08]) compared with PP
      (2.85 [0.56; 5.08]). Likewise, Clinical Global Impression-Severity improved more
      in the AOM 400 group (-0.59 [-0.71; -0.47]) compared with PP group (-0.37 [-0.46;
      -0.27]). Therefore, the analysis of data from stabilized patients with
      schizophrenia in the QUALIFY study indicated that AOM 400 is associated with
      lower health-care costs and greater effectiveness compared with PP and thus
      represents the economically dominant strategy.

PMID- 27708679
TI  - Development of foraging skills in two orangutan populations: needing to learn or
      needing to grow?
AB  - BACKGROUND: Orangutans have one of the slowest-paced life histories of all
      mammals. Whereas life-history theory suggests that the time to reach adulthood is
      constrained by the time needed to reach adult body size, the needing-to-learn
      hypothesis instead suggests that it is limited by the time needed to acquire
      adult-level skills. To test between these two hypotheses, we compared the
      development of foraging skills and growth trajectories of immature wild
      orangutans in two populations: at Tuanan (Pongo pygmaeus wurmbii), Borneo, and
      Suaq Balimbing (Pongo abelii), Sumatra. We collected behavioral data on diet
      repertoire, feeding rates and ranging competence during focal follows, and
      estimated growth through non-invasive laser photogrammetry. RESULTS: We found
      that adult-like diet repertoires are attained around the age of weaning and that
      female immatures increase their repertoire size faster than their male peers.
      Adult-level feeding rates of easy techniques are reached just after weaning, but
      several years later for more difficult techniques, albeit always before adulthood
      (i.e. age at first reproduction). Independent immatures had faster feeding rates
      for easy to process items than their mothers, with male immatures achieving
      faster feeding rates earlier in development relative to females. Sumatran
      immatures reach adult-level feeding rates 2-3 years later than their Bornean
      peers, in line with their higher dietary complexity and later weaning. The range
      use competence of independently ranging and weaned immatures is similar to that
      of adult females. Body size measurements showed, immatures grow until female age
      of first reproduction. CONCLUSIONS: In conclusion, unlike in humans, orangutan
      foraging skills are in place prior to reproduction. Growth trajectories suggest
      that energetic constraints, rather than skills, best explain the length of
      immaturity. However, skill competence for dietary independence is reached later
      where the adult niche is more complex, which is consistent with the relatively
      later weaning age with increasing brain size found generally in primates, and
      apes in particular.

PMID- 27708680
TI  - The cephalopod arm crown: appendage formation and differentiation in the Hawaiian
      bobtail squid Euprymna scolopes.
AB  - BACKGROUND: Cephalopods are a highly derived class of molluscs that adapted their
      body plan to a more active and predatory lifestyle. One intriguing adaptation is
      the modification of the ventral foot to form a bilaterally symmetric arm crown,
      which constitutes a true morphological novelty in evolution. In addition, this
      structure shows many diversifications within the class of cephalopods and
      therefore offers an interesting opportunity to study the molecular underpinnings
      of the emergence of phenotypic novelties and their diversification. Here we use
      the sepiolid Euprymna scolopes as a model to study the formation and
      differentiation of the decabrachian arm crown, which consists of four pairs of
      sessile arms and one pair of retractile tentacles. We provide a detailed
      description of arm crown formation in order to understand the basic morphology
      and the developmental dynamics of this structure. RESULTS: We show that the
      morphological formation of the cephalopod appendages occurs during distinct
      phases, including outgrowth, elongation, and tissue differentiation. Early
      outgrowth is characterized by uniform cell proliferation, while the elongation of
      the appendages initiates tissue differentiation. The latter progresses in a
      gradient from proximal to distal, whereas cell proliferation becomes restricted
      to the distal-most end of the arm. Differences in the formation of arms and
      tentacles exist, with the tentacles showing an expedite growth rate and higher
      complexity at younger stages. CONCLUSION: The early outgrowth and differentiation
      of the E. scolopes arm crown shows similarities to the related, yet derived
      cephalopod Octopus vulgaris. Parallels in the growth and differentiation of
      appendages seem to exist throughout the animal kingdom, raising the question of
      whether these similarities reflect a recruitment of similar molecular patterning
      pathways.

PMID- 27708678
TI  - Current trends and intricacies in the management of HIV-associated pulmonary
      tuberculosis.
AB  - Human immunodeficiency virus (HIV) epidemic has undoubtedly increased the
      incidence of tuberculosis (TB) globally, posing a formidable global health
      challenge affecting 1.2 million cases. Pulmonary TB assumes utmost significance
      in the programmatic perspective as it is readily transmissible as well as easily
      diagnosable. HIV complicates every aspect of pulmonary tuberculosis from
      diagnosis to treatment, demanding a different approach to effectively tackle both
      the diseases. In order to control these converging epidemics, it is important to
      diagnose early, initiate appropriate therapy for both infections, prevent
      transmission and administer preventive therapy. Liquid culture methods and
      nucleic acid amplification tests for TB confirmation have replaced conventional
      solid media, enabling quicker and simultaneous detection of mycobacterium and its
      drug sensitivity profile Unique problems posed by the syndemic include Acquired
      rifampicin resistance, drug-drug interactions, malabsorption of drugs and immune
      reconstitution inflammatory syndrome or paradoxical reaction that complicate dual
      and concomitant therapy. While the antiretroviral therapy armamentarium is
      constantly reinforced by discovery of newer and safer drugs every year, only a
      few drugs for anti tuberculosis treatment have successfully emerged. These
      include bedaquiline, delamanid and pretomanid which have entered phase III B
      trials and are also available through conditional access national programmes. The
      current guidelines by WHO to start Antiretroviral therapy irrespective of CD4+
      cell count based on benefits cited by recent trials could go a long way in
      preventing various complications caused by the deadly duo. This review provides a
      consolidated gist of the advancements, concepts and updates that have emerged in
      the management of HIV-associated pulmonary TB for maximizing efficacy, offering
      latest solutions for tackling drug-drug interactions and remedial measures for
      immune reconstitution inflammatory syndrome.

PMID- 27708681
TI  - Comparative localization of serotonin-like immunoreactive cells in Thaliacea
      informs tunicate phylogeny.
AB  - BACKGROUND: Thaliaceans is one of the understudied classes of the phylum
      Tunicata. In particular, their phylogenetic relationships remain an issue of
      debate. The overall pattern of serotonin (5-HT) distribution is an excellent
      biochemical trait to interpret internal relationships at order level. In the
      experiments reported here we compared serotonin-like immunoreactivity at
      different life cycle stages of two salpid, one doliolid, and one pyrosomatid
      species. This multi-species comparison provides new neuroanatomical data for
      better resolving the phylogeny of the class Thaliacea. RESULTS: Adults of all
      four examined thaliacean species exhibited serotonin-like immunoreactivity in
      neuronal and non-neuronal cell types, whose anatomical position with respect to
      the nervous system is consistently identifiable due to alpha-tubulin
      immunoreactivity. The results indicate an extensive pattern that is consistent
      with the presence of serotonin in cell bodies of variable morphology and
      position, with some variation within and among orders. Serotonin-like
      immunoreactivity was not found in immature forms such as blastozooids (Salpida),
      tadpole larvae (Doliolida) and young zooids (Pyrosomatida). CONCLUSIONS:
      Comparative anatomy of serotonin-like immunoreactivity in all three thaliacean
      clades has not been reported previously. These results are discussed with regard
      to studies of serotonin-like immunoreactivity in adult ascidians. Lack of
      serotonin-like immunoreactivity in the endostyle of Salpida and Doliolida
      compared to Pyrosomella verticillata might be the result of secondary loss of
      serotonin control over ciliary beating and mucus secretion. These data, when
      combined with other plesiomorphic characters, support the hypothesis that
      Pyrosomatida is basal to these clades within Phlebobranchiata and that Salpida
      and Doliolida constitute sister-groups.

PMID- 27708682
TI  - Hepatic adaptations to maintain metabolic homeostasis in response to fasting and
      refeeding in mice.
AB  - BACKGROUND: The increased incidence of obesity and associated metabolic diseases
      has driven research focused on genetically or pharmacologically alleviating
      metabolic dysfunction. These studies employ a range of fasting-refeeding models
      including 4-24 h fasts, "overnight" fasts, or meal feeding. Still, we lack
      literature that describes the physiologically relevant adaptations that accompany
      changes in the duration of fasting and re-feeding. Since the liver is central to
      whole body metabolic homeostasis, we investigated the timing of the fast-induced
      shift toward glycogenolysis, gluconeogenesis, and ketogenesis and the meal
      induced switch toward glycogenesis and away from ketogenesis. METHODS: Twelve to
      fourteen week old male C57BL/6J mice were fasted for 0, 4, 8, 12, or 16 h and
      sacrificed 4 h after lights on. In a second study, designed to understand the
      response to a meal, we gave fasted mice access to feed for 1 or 2 h before
      sacrifice. We analyzed the data using mixed model analysis of variance. RESULTS:
      Fasting initiated robust metabolic shifts, evidenced by changes in serum glucose,
      non-esterified fatty acids (NEFAs), triacylglycerol, and beta-OH butyrate, as
      well as, liver triacylglycerol, non-esterified fatty acid, and glycogen content.
      Glycogenolysis is the primary source to maintain serum glucose during the first 8
      h of fasting, while de novo gluconeogenesis is the primary source thereafter. The
      increase in serum beta-OH butyrate results from increased enzymatic capacity for
      fatty acid flux through beta-oxidation and shunting of acetyl-CoA toward ketone
      body synthesis (increased CPT1 (Carnitine Palmitoyltransferase 1) and HMGCS2 (3
      Hydroxy-3-Methylglutaryl-CoA Synthase 2) expression, respectively). In opposition
      to the relatively slow metabolic adaptation to fasting, feeding of a meal results
      in rapid metabolic changes including full depression of serum beta-OH butyrate
      and NEFAs within an hour. CONCLUSIONS: Herein, we provide a detailed description
      of timing of the metabolic adaptations in response to fasting and re-feeding to
      inform study design in experiments of metabolic homeostasis. Since fasting and
      obesity are both characterized by elevated adipose tissue lipolysis, hepatic
      lipid accumulation, ketogenesis, and gluconeogenesis, understanding the drivers
      behind the metabolic shift from the fasted to the fed state may provide targets
      to limit aberrant gluconeogenesis and ketogenesis in obesity.

PMID- 27708684
TI  - The impact of protein quality on the promotion of resistance exercise-induced
      changes in muscle mass.
AB  - Protein supplementation during resistance exercise training augments hypertrophic
      gains. Protein ingestion and the resultant hyperaminoacidemia provides the
      building blocks (indispensable amino acids - IAA) for, and also triggers an
      increase in, muscle protein synthesis (MPS), suppression of muscle protein
      breakdown (MPB), and net positive protein balance (i.e., MPS > MPB). The key
      amino acid triggering the rise in MPS is leucine, which stimulates the
      mechanistic target of rapamycin complex-1, a key signalling protein, and triggers
      a rise in MPS. As such, ingested proteins with a high leucine content would be
      advantageous in triggering a rise in MPS. Thus, protein quality (reflected in IAA
      content and protein digestibility) has an impact on changes in MPS and could
      ultimately affect skeletal muscle mass. Protein quality has been measured by the
      protein digestibility-corrected amino acid score (PDCAAS); however, the
      digestible indispensable amino acid score (DIAAS) has been recommended as a
      better method for protein quality scoring. Under DIAAS there is the recognition
      that amino acids are individual nutrients and that protein quality is contingent
      on IAA content and ileal (as opposed to fecal) digestibility. Differences in
      protein quality may have important ramifications for exercise-induced changes in
      muscle mass gains made with resistance exercise as well as muscle remodelling.
      Thus, the purpose of this review is a critical appraisal of studies examining the
      effects of protein quality in supplementation on changes in muscle mass and
      strength as well as body composition during resistance training.

PMID- 27708683
TI  - Microarray analysis of gene expression in liver, adipose tissue and skeletal
      muscle in response to chronic dietary administration of NDGA to high-fructose fed
      dyslipidemic rats.
AB  - Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote Bush, has been
      shown to have profound effects on the core components of metabolic syndrome,
      including lowering of blood glucose, free fatty acids and triglyceride levels,
      attenuating elevated blood pressure in several rodent models of dyslipidemia, and
      improving body weight, insulin resistance, diabetes and hypertension. In the
      present study, a high-fructose diet fed rat model of hypertriglyceridemia,
      dyslipidemia, insulin resistance and hepatic steatosis was employed to
      investigate the global transcriptional changes in the lipid metabolizing pathways
      in three insulin sensitive tissues: liver, skeletal muscle and adipose tissue in
      response to chronic dietary administration of NDGA. Sprague-Dawley male rats (SD)
      were fed a chow (control) diet, high-fructose diet (HFrD) or HFrD supplemented
      with NDGA (2.5 g/kg diet) for eight weeks. Dietary administration of NDGA
      decreased plasma levels of TG, glucose, and insulin, and attenuated hepatic TG
      accumulation. DNA microarray expression profiling indicated that dietary
      administration of NDGA upregulated the expression of certain genes involved in
      fatty acid oxidation and their transcription regulator, PPARalpha, decreased the
      expression of a number of lipogenic genes and relevant transcription factors, and
      differentially impacted the genes of fatty acid transporters, acetyl CoA
      synthetases, elongases, fatty acid desaturases and lipid clearance proteins in
      liver, skeletal muscle and adipose tissues. These findings suggest that NDGA
      ameliorates hypertriglyceridemia and steatosis primarily by inhibiting
      lipogenesis and enhancing fatty acid catabolism in three major insulin responsive
      tissues by altering the expression of key enzyme genes and transcription factors
      involved in de novo lipogenesis and fatty acid oxidation.

PMID- 27708687
TI  - Unveiling consumer's privacy paradox behaviour in an economic exchange.
AB  - Privacy paradox is of great interest to IS researchers and firms gathering
      personal information. It has been studied from social, behavioural, and economic
      perspectives independently. However, prior research has not examined the degrees
      of influence these perspectives contribute to the privacy paradox problem. We
      combine both economic and behavioural perspectives in our study of the privacy
      paradox with a price valuation of personal information through an economic
      experiment combined with a behavioural study on privacy paradox. Our goal is to
      reveal more insights on the privacy paradox through economic valuation on
      personal information. Results indicate that general privacy concerns or
      individual disclosure concerns do not have a significant influence on the price
      valuation of personal information. Instead, prior disclosure behaviour in
      specific scenario, like with healthcare providers or social networks, is a better
      indicator of consumer price valuations.

PMID- 27708686
TI  - A 13-Weeks Mindfulness Based Pain Management Program Improves Psychological
      Distress in Patients with Chronic Pain Compared with Waiting List Controls.
AB  - BACKGROUND: Eradication of pain is seldom an option in chronic pain management.
      Hence, mindfulness meditation has become popular in pain management. OBJECTIVE:
      This pilot study compared the effect of a 13-weeks cognitive behavioural therapy
      program with integrated mindfulness meditation (CBTm) in patients with chronic
      non-malignant pain with a control condition. It was hypothesised that the CBTm
      program would reduce pain intensity and psychological distress compared to the
      control condition and that level of mindfulness and acceptance both would be
      associated with the reduction in pain intensity and psychological distress.
      METHODS: A case-control design was used and data were collected from a
      convenience sample of 70 patients with chronic non-malignant pain. Fifty patients
      were consecutively recruited to the CBTm intervention and 20 patients matched
      waiting list controls. Assessments of clinical pain and psychological distress
      were performed in both groups at baseline and after 13 weeks. RESULTS: The CBTm
      program reduced depression, anxiety and pain-catastrophizing compared with the
      control group. Increased level of mindfulness and acceptance were associated with
      change in psychological distress with the exception of depression, which was only
      associated with change in level of mindfulness. Surprisingly, changes in level of
      mindfulness did not correlate with changes in acceptance. CONCLUSIONS: The
      results indicate that different mechanisms are targeted with cognitive
      behavioural therapy and mindfulness. The finding that changes in level of
      mindfulness did not correlate with changes in acceptance may indicate that
      acceptance is not a strict prerequisite for coping with pain related distress.

PMID- 27708685
TI  - Animal models of metabolic syndrome: a review.
AB  - Metabolic syndrome (MetS) consists of several medical conditions that
      collectively predict the risk for cardiovascular disease better than the sum of
      individual conditions. The risk of developing MetS in human depends on synergy of
      both genetic and environmental factors. Being a multifactorial condition with
      alarming rate of prevalence nowadays, establishment of appropriate experimental
      animal models mimicking the disease state in humans is crucial in order to solve
      the difficulties in evaluating the pathophysiology of MetS in human. This review
      aims to summarize the underlying mechanisms involved in the pathophysiology of
      dietary, genetic, and pharmacological models of MetS. Furthermore, we will
      discuss the usefulness, suitability, pros and cons of these animal models. Even
      though numerous animal models of MetS have been established, further
      investigations on the invention of new animal model and clarification of
      plausible mechanisms are still necessary to confer a better understanding to
      researchers on the selection of animal models for their studies.

PMID- 27708688
TI  - The CSL proteins, versatile transcription factors and context dependent
      corepressors of the notch signaling pathway.
AB  - The Notch signaling pathway is a reiteratively used cell to cell communication
      pathway that triggers pleiotropic effects. The correct regulation of the pathway
      permits the efficient regulation of genes involved in cell fate decision
      throughout development. This activity relies notably on the CSL proteins, (an
      acronym for CBF-1/RBPJ-kappa in Homo sapiens/Mus musculus respectively,
      Suppressor of Hairless in Drosophila melanogaster, Lag-1 in Caenorhabditis
      elegans) which is the unique transcription factor and DNA binding protein
      involved in this pathway. The CSL proteins have the capacity to recruit
      activation or repression complexes according to the cellular context. The aim of
      this review is to describe the different co-repressor proteins that interact
      directly with CSL proteins to form repression complexes thereby regulating the
      Notch signaling pathway in animal cells to give insights into the paralogous
      evolution of these co-repressors in higher eumetazoans and their subsequent
      effects at developmental processes.

PMID- 27708689
TI  - An efficient algorithm for protein structure comparison using elastic shape
      analysis.
AB  - BACKGROUND: Protein structure comparison play important role in in silico
      functional prediction of a new protein. It is also used for understanding the
      evolutionary relationships among proteins. A variety of methods have been
      proposed in literature for comparing protein structures but they have their own
      limitations in terms of accuracy and complexity with respect to computational
      time and space. There is a need to improve the computational complexity in
      comparison/alignment of proteins through incorporation of important biological
      and structural properties in the existing techniques. RESULTS: An efficient
      algorithm has been developed for comparing protein structures using elastic shape
      analysis in which the sequence of 3D coordinates atoms of protein structures
      supplemented by additional auxiliary information from side-chain properties are
      incorporated. The protein structure is represented by a special function called
      square-root velocity function. Furthermore, singular value decomposition and
      dynamic programming have been employed for optimal rotation and optimal matching
      of the proteins, respectively. Also, geodesic distance has been calculated and
      used as the dissimilarity score between two protein structures. The performance
      of the developed algorithm is tested and found to be more efficient, i.e.,
      running time reduced by 80-90 % without compromising accuracy of comparison when
      compared with the existing methods. Source codes for different functions have
      been developed in R. Also, user friendly web-based application called ProtSComp
      has been developed using above algorithm for comparing protein 3D structures and
      is accessible free. CONCLUSIONS: The methodology and algorithm developed in this
      study is taking considerably less computational time without loss of accuracy
      (Table 2). The proposed algorithm is considering different criteria of
      representing protein structures using 3D coordinates of atoms and inclusion of
      residue wise molecular properties as auxiliary information.

PMID- 27708691
TI  - Authentication of Acori Tatarinowii Rhizoma (Shi Chang Pu) and its adulterants by
      morphological distinction, chemical composition and ITS sequencing.
AB  - BACKGROUND: Acori Tatarinowii Rhizoma (ATR; rhizome of Acorus tatarinowii Schott)
      (Shi Chang Pu) is widely used in Chinese medicine (CM) to resuscitate, calm the
      mind, resolve shi (dampness) and harmonize the wei (stomach). Seven different
      species have been identified as belonging to the genus Acorus, all of which can
      be found in China. However, it can be difficult to distinguish the different
      species of Acorus because of their morphological similarities. The aim of this
      study was to authenticate Acorus species using macroscopic and microscopic
      techniques, chemical analysis and DNA authentication and to compare the
      resolution power and reliability of these different methods. METHODS: Four
      batches of ATR, Acori Graminei Rhizoma (AGR), Acori Calami Rhizoma (ACR) and
      Anemones Altaicae Rhizoma (AAR) (totaling 16 samples) were collected from Hong
      Kong and mainland China. The major characteristic features of these Acorus
      species were identified by macroscopic and microscopic examination. The
      identified samples were also analyzed by UHPLC analysis. Principal component
      analysis (PCA) and hierarchal clustering analysis (HCA) on UHPLC results were
      used to differentiate between the samples. An internal transcribed spacer (ITS)
      was selected as a molecular probe and a modified DNA extraction method was
      developed to obtain trace amounts of DNA from the different Acorus species. All
      extracted DNA sequences were edited by Bioedit and aligned with the ClustalW. And
      the sequence distances were calculated using the Maximum Parsimony method.
      RESULTS: Macroscopic and microscopic analyses allowed for AAR to be readily
      distinguished from ATR, AGR and ACR. However, it was difficult to distinguish
      between ATR, AGR and ACR because of their similar morphological features.
      Chemical profiling revealed that alpha- and beta-asarone were only found in the
      ATR, AGR and ACR samples, but not in the AAR samples. Furthermore, PCA and HCA
      allowed for the differentiation of these three species based on their asarone
      contents. Morphological authentication and chemical profiling allowed for the
      partial differentiation of ATR, AGR ACR and AAR. DNA analysis was the only method
      capable of accurately differentiating between all four species. CONCLUSION: DNA
      authentication exhibited higher resolution power and reliability than
      conventional morphological identification and UHPLC in differentiating between
      different Acorus species.

PMID- 27708690
TI  - Validity of predictive factors of acute complicated appendicitis.
AB  - BACKGROUND: Our previous retrospective study revealed the three preoperative
      predictors of complicated appendicitis (perforated or gangrenous appendicitis),
      which are body temperature >=37.4  degrees C, C-reactive protein >=4.7 mg/dl, and
      fluid collection surrounding the appendix on computed tomography. We reported
      here an additional prospective study to verify our ability to predict complicated
      appendicitis using the three preoperative predictors and thus facilitate better
      informed decisions regarding emergency surgery during night or holiday shifts.
      METHODS: We prospectively evaluated 116 adult patients who underwent surgery for
      acute appendicitis from January 2013 to October 2014. Ninety patients with one or
      more predictive factors of complicated appendicitis underwent immediate surgery
      regardless of the time of patient's presentation. Twenty-six patients had no
      predictive factors and thus were suspected to have uncomplicated appendicitis. Of
      the 26 patients, 14 who presented to our hospital during office hours underwent
      immediate surgery. The other 12 patients who presented to our hospital at night
      or on a holiday underwent short, in-hospital delayed surgery during office hours.
      RESULTS: All patients with no predictive factors had uncomplicated appendicitis,
      whereas 37 %, 81 %, and 100 % of patients with one, two, or all three factors,
      respectively, were diagnosed with complicated appendicitis. The emergency
      operation rate decreased from 83 % before to 58 % after adopting this scoring
      system, but no significant differences in postoperative complication rates and
      hospitalization periods were observed. CONCLUSIONS: The above-mentioned
      preoperative factors predictive of complicated appendicitis preoperatively are
      useful for emergency surgical decisions and reduce the burdens on surgeons and
      medical staff.

PMID- 27708694
TI  - Full component analysis of Tianma-Gouteng-Yin.
AB  - BACKGROUND: Tianma-Gouteng-Yin (TGY), which is common Chinese medicine
      formulation consisting of 11 different herbs and being used in China for the
      treatment of Parkinson's disease, inflammatory conditions and cardiovascular
      diseases, was selected for full component analysis. The aim of this study was to
      quantitatively analyze the chemical profiles of ten commercial TGY samples and
      one sample produced in our laboratory. METHODS: Ultra-high performance liquid
      chromatography (UHPLC) coupled with quadrupole-tandem time-of-flight mass
      spectrometry (Q-TOF-MS) was used to analyze the non-saccharide small molecule
      components of the different TGY samples. The established method was validated in
      terms of its linearity, sensitivity, precision, accuracy and stability. High
      performance liquid chromatography coupled with evaporative light scattering
      detection (HPLC-ELSD) was also used to quantify three major saccharides
      (fructose, glucose and sucrose). RESULTS: The relative standard deviations for
      the precision, repeatability and stability of these compounds were less than 5 %,
      while the accuracy of the method was 95-105 %. Twenty-eight of the compounds
      found in TGY were successfully identified, with 20 being quantified. The
      macromolecules present in these samples were also identified using an ethanol
      precipitation method, representing 294.68-696.64 mg/g of the total material
      depending on the batch. Notably, the components identified using this method
      represented up to 78 % of the total weight of the TGY samples. CONCLUSIONS: The
      developed UHPLC/Q-TOF-MS and HPLC-ELSD methods successfully identified 28 of the
      complex compounds found in TGY.

PMID- 27708692
TI  - In silico profiling for secondary metabolites from Lepidium meyenii (maca) by the
      pharmacophore and ligand-shape-based joint approach.
AB  - BACKGROUND: Lepidium meyenii Walpers (maca) is an herb known as a traditional
      nutritional supplement and widely used in Peru, North America, and Europe to
      enhance human fertility and treat osteoporosis. The secondary metabolites of
      maca, namely, maca alkaloids, macaenes, and macamides, are bioactive compounds,
      but their targets are undefined. METHODS: The pharmacophore-based PharmaDB
      targets database screening joint the ligand shape similarity-based WEGA
      validation approach is proposed to predict the targets of these unique
      constituents and was performed using Discovery Studio 4.5 and PharmaDB. A
      compounds-targets-diseases network was established using Cytoscape 3.2. These
      suitable targets and their genes were calculated and analyzed using ingenuity
      pathway analysis and GeneMANIA. RESULTS: Certain targets were identified in
      osteoporosis (8 targets), prostate cancer (9 targets), and kidney diseases (11
      targets). This was the first study to identify the targets of these bioactive
      compounds in maca for cardiovascular diseases (29 targets). The compound with the
      most targets (46) was an amide alkaloid (MA-24). CONCLUSION: In silico target
      fishing identified maca's traditional effects on treatment and prevention of
      osteoporosis, prostate cancer, and kidney diseases, and its potential function of
      treating cardiovascular diseases, as the most important of this herb's possible
      activities.

PMID- 27708695
TI  - A questionnaire survey regarding the support needed by Yogo teachers to take care
      of students suspected of having eating disorders (second report).
AB  - BACKGROUND: The lowering of the age of onset and chronicity have been key
      problems related to eating disorders (EDs). As the proportion of teens in the
      estimated onset ages has increased, it has become important to detect students
      with EDs and to clarify how they can be supported. Though epidemiological surveys
      of Yogo teachers (school nurse/health science teachers) have been conducted to
      inquire about the number of such students, none of these were done according to
      ED type based on DSM-5. Thus, we conducted a wide area survey in Japan with the
      goal of proposing a better framework of support for Yogo teachers in their
      efforts to care for students with EDs. METHODS: A questionnaire survey organized
      by ED type (based on DSM-5) was administered to Yogo teachers working at
      elementary/junior high/senior high/special needs schools in four prefectures of
      Japan in 2015, and 1,886 responses were obtained. Based on the results, the
      encounter rates (the proportion of Yogo teachers who had encountered a student
      with an ED) were calculated, and factors that could affect the rates were
      examined by logistic regression analysis. RESULTS: The order of the encounter
      rates of the ED types was as follows: Anorexia Nervosa (AN) > Bulimia Nervosa
      (BN) > Avoidant/Restrictive Food Intake Disorder (ARFID) > Binge Eating Disorder
      (BED) > Others. The factors significantly affecting the rates were "location,
      school type, number of students, experience years, and AN knowledge" for AN,
      "school type, experience years, and BN knowledge" for BN, "school type,
      experience years, and BED knowledge" for BED, "location, experience years, and
      ARFID knowledge" for ARFID, and "school type, experience years, and Others
      knowledge" for Others. CONCLUSIONS: Because the encounter rate of AN was the
      highest, providing support for AN would be the most effective. Moreover, one
      factor that affected the encounter rate of all ED types was ED knowledge. In
      addition to this, senior high schools had the highest encounter rates for AN, BN
      and BED, and special needs schools had the highest rates for Others. These
      findings imply that, in order to detect and support ED students at an early
      stage, it is necessary to offer knowledge of the most prevalent ED types to Yogo
      teachers at the corresponding school type.

PMID- 27708693
TI  - Anti-cancer effects of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan).
AB  - Gynostemma pentaphyllum (Thunb.) Makino (GpM) (Jiaogulan) has been widely used in
      Chinese medicine for the treatment of several diseases, including hepatitis,
      diabetes and cardiovascular disease. Furthermore, GpM has recently been shown to
      exhibit potent anti-cancer activities. In this review, we have summarized recent
      research progress on the anti-cancer activities and mechanisms of action of GpM,
      as well as determining the material basis for the anti-cancer effects of GpM by
      searching the PubMed, Web of Science and China National Knowledge Infrastructure
      databases. The content of this review is based on studies reported in the
      literature pertaining to the chemical components or anti-cancer effects of GpM up
      until the beginning of August, 2016. This search of the literature revealed that
      more than 230 compounds have been isolated from GpM, and that most of these
      compounds (189) were saponins, which are also known as gypenosides. All of the
      remaining compounds were classified as sterols, flavonoids or polysaccharides.
      Various extracts and fractions of GpM, as well as numerous pure compounds
      isolated from this herb exhibited inhibitory activity towards the proliferation
      of cancer cells in vitro and in vivo. Furthermore, the results of several
      clinical studies have shown that GpM formula could have potential curative
      effects on cancer. Multiple mechanisms of action have been proposed regarding the
      anti-cancer activities of GpM, including cell cycle arrest, apoptosis, inhibition
      of invasion and metastasis, inhibition of glycolysis and immunomodulating
      activities.

PMID- 27708696
TI  - Differences in tobacco smoking prevalence and frequency between adolescent
      Palestine refugee and non-refugee populations in Jordan, Lebanon, Syria, and the
      West Bank: cross-sectional analysis of the Global Youth Tobacco Survey.
AB  - BACKGROUND: Evidence is conflicting as to the whether tobacco smoking prevalence
      is higher in refugee than non-refugee populations. The aim of this study was to
      compare the prevalence and frequency of tobacco smoking in Palestine refugee and
      non-refugee adolescent populations in the Middle East. METHODS: We conducted a
      cross-sectional analysis of the Global Youth Tobacco Survey (GYTS) conducted in
      Jordan, Lebanon, Syria, and the West Bank among adolescent Palestine refugees and
      non-refugees. Age- and sex-adjusted regression models assessed the association
      between refugee status and current (past-30 day) tobacco use prevalence and
      frequency. RESULTS: Prevalence estimates for current tobacco smoking were similar
      between Palestine refugee and non-refugee groups in Jordan (26.7 % vs. 24.0 %),
      Lebanon (39.4 % vs. 38.5 %), and the West Bank (39.5 % vs. 38.4 %). In Syria,
      Palestine refugees had nearly twice the odds of current tobacco smoking compared
      to non-refugees (23.2 % vs. 36.6 %, AOR 1.96, 95 % CI 1.46-2.62). Palestine
      refugees consumed more cigarettes per month than non-refugees in Lebanon (beta
      0.57, 95 % CI 0.17-0.97) and Palestine refugees consumed more waterpipe tobacco
      per month than non-refugees in Syria (beta 0.40, 95 % CI 0.19-0.61) and the West
      Bank (beta 0.42, 95 % CI 0.21-0.64). CONCLUSIONS: Current tobacco smoking
      prevalence is in excess of 20 % in both adolescent Palestine refugee and non
      refugee populations in Middle Eastern countries, however Palestine refugees may
      smoke tobacco more frequently than non-refugees. Comparison of simple prevalence
      estimates may therefore mask important differences in tobacco use patterns within
      population groups.

PMID- 27708697
TI  - Information systems for mental health in six low and middle income countries:
      cross country situation analysis.
AB  - BACKGROUND: Research on information systems for mental health in low and middle
      income countries (LMICs) is scarce. As a result, there is a lack of reliable
      information on mental health service needs, treatment coverage and the quality of
      services provided. METHODS: With the aim of informing the development and
      implementation of a mental health information sub-system that includes reliable
      and measurable indicators on mental health within the Health Management
      Information Systems (HMIS), a cross-country situation analysis of HMIS was
      conducted in six LMICs (Ethiopia, India, Nepal, Nigeria, South Africa and
      Uganda), participating in the 'Emerging mental health systems in low and middle
      income countries' (Emerald) research programme. A situation analysis tool was
      developed to obtain and chart information from documents in the public domain. In
      circumstances when information was inadequate, key government officials were
      contacted to verify the data collected. In this paper we compare the baseline
      policy context, human resources situation as well as the processes and mechanisms
      of collecting, verifying, reporting and disseminating mental health related HMIS
      data. RESULTS: The findings suggest that countries face substantial policy, human
      resource and health governance challenges for mental health HMIS, many of which
      are common across sites. In particular, the specific policies and plans for the
      governance and implementation of mental health data collection, reporting and
      dissemination are absent. Across sites there is inadequate infrastructure, few
      HMIS experts, and inadequate technical support and supervision to junior staff,
      particularly in the area of mental health. Nonetheless there are also strengths
      in existing HMIS where a few mental health morbidity, mortality, and system level
      indicators are collected and reported. CONCLUSIONS: Our study indicates the need
      for greater technical and resources input to strengthen routine HMIS and develop
      standardized HMIS indicators for mental health, focusing in particular on
      indicators of coverage and quality to facilitate the implementation of the WHO
      mental health action plan 2013-2020.

PMID- 27708699
TI  - Brunei's teacher education programs: insights into students' coping and help
      seeking strategies to challenges.
AB  - BACKGROUND: Brunei started implementing its two main reformed teacher education
      programs, MTeach and MEd, in 2009. The reasons for these innovations included
      upgrading the standard of teacher training, increasing teaching effectiveness,
      and improving the quality of education in the country. The purpose of this study
      was to determine how student teachers coped with and sought help on the
      challenging programs. METHODS: Using an online survey design, 76 randomly
      selected recent graduate teachers responded appropriately to questionnaires
      administered to them by email. The obtained quantitative research information
      included demographic, coping, and help-seeking data, all analyzed by SPSS Version
      22. RESULTS: Participants endorsed both the productive and nonproductive coping
      strategies. In addition, they depended more on peers, teachers and internet
      sources for help. Four major findings were obtained. First, task-oriented coping
      was the most important and significant predictor of success on the MTeach and MEd
      programs. Second, females had a higher likelihood of success compared to males
      (OR = 22.760, 95 % CI for OR = 12.848-40.320). Third, students who consulted
      relevant internet resources had higher odds for succeeding compared to those who
      did not (OR = 2.237, 95 % CI 1.196-4.183). Fourth, less-able students who
      collaboratively worked with the more-able peers were nearly two times more likely
      to perform better than those who did not (OR = 1.982, 95 % CI 1.082-3.630).
      CONCLUSIONS: Coping and help-seeking were positively and significantly related to
      academic achievement on the two Brunei main teacher education programs. Evidence
      from the present study suggested that vulnerable and at-risk trainee teachers
      needed appropriate interventions (educational, counseling and psychotherapy)
      related to effective use of task-oriented coping and seeking help via cooperative
      learning, internet sources, and teacher consultations,. Further research with
      interview probes was recommended to gain additional information on the problem
      and its solutions.

PMID- 27708698
TI  - Achievements of the Australian Access to Allied Psychological Services (ATAPS)
      program: summarising (almost) a decade of key evaluation data.
AB  - BACKGROUND: Introduced in July 2001, Australian Access to Allied Psychological
      Services (ATAPS) was the inaugural national policy initiative to provide
      community access to government-funded psychological services in primary care. Our
      aim was to examine the achievements of ATAPS in relation to its stated objectives
      using a set of indicators that largely drew on data from a minimum data set that
      we designed for the evaluation of ATAPS. METHODS: We used de-identified
      professional-, consumer- and session-level data from the minimum dataset, and
      secondary analyses of our quantitative and qualitative data collected for a
      series of specific evaluation studies. Available data covered the period from 1
      July 2003 to 31 December 2012. RESULTS: Approximately 350,000 referrals were made
      to the ATAPS program over the 9.5 year analysis period, 79 % of which resulted in
      services. Over 1.4 million sessions were offered. Overall, 29 % of consumers were
      male, 4 % children, and 3 % Aboriginal people; 54 % of consumers had depression
      and 41 % an anxiety disorder; at least 60 % were on low incomes; and around 50 %
      resided outside of major cities. The most common interventions delivered were
      cognitive and behavioural therapies. Selected outcome measures indicated
      improvement in mental health symptoms. CONCLUSIONS: Access to Allied
      Psychological Services achieved its objectives within a decade of operation. The
      program delivered evidence-based services to a substantial number of consumers
      who were disadvantaged and historically would not have accessed services.
      Importantly, where data were available, there were indications that ATAPS
      achieved positive clinical outcomes for consumers. This suggests that ATAPS
      carved an important niche by successfully addressing unmet need of hard-to-reach
      consumers and through means that were not available via other programs. It will
      be interesting to see the effects from July 2016 of the reform of ATAPS, which
      will see ATAPS subsumed under psychological services commissioned by regional
      primary care organisations.

PMID- 27708700
TI  - Fluid management in pre-eclampsia.
AB  - Intravenous fluid given to women with pre-eclampsia may be a necessary form of
      treatment; however, intravenous fluid therapy can also cause iatrogenic pulmonary
      oedema. The indications for the use of intravenous fluids, the titration of the
      amount of fluid given and the use of invasive monitoring have not been subject to
      adequate examination in randomised studies. Clinical experience, combined with
      available evidence and a reasoned approach are the basis for a suggested
      management algorithm.

PMID- 27708702
TI  - Marfan's syndrome and other aortopathies in pregnancy.
AB  - Aortopathies, or disease affecting the aorta, are associated with a significant
      mortality risk for the mother and foetus during pregnancy because of an increased
      rate of aortic dissection. The hereditary aortopathies; Marfan's syndrome,
      bicuspid aortic valve, Loeys-Dietz syndrome, Ehlers-Danlos (type IV) syndrome,
      Turner's syndrome and nonsyndromic familial thoracic aortic aneurysm and
      dissection are all associated with an increased risk of aortic dissection
      particularly during the third trimester and early postpartum period. Maternal
      outcome in pregnancy depends on the underlying disorder and the aortic dimensions
      prior to pregnancy. The foetus has up to 50% chance of inheriting the underlying
      genetic defect. Vasculitis, particularly Takayasu's arteritis may also be a
      problem in pregnancy and predispose to aortic dissection. Prepregnancy review,
      including careful assessment of the aorta and prophylactic aortic surgery for an
      aortic aneurysm may reduce the risk of aortic dissection in pregnancy for some of
      the aortopathies but for women with Marfan's syndrome, Loeys-Dietz syndrome and
      Ehlers-Danlos (vascular type IV) who have had surgery, the risk of death remains
      high. A subgroup of women with Marfan's syndrome or a bicuspid aortic valve and
      normal aortic dimensions prepregnancy should do well in a pregnancy.
      Multidisciplinary pregnancy care with agreement on pregnancy follow-up, delivery
      and postpartum care with a crisis plan for an aortic dissection can improve
      pregnancy outcome and ensure prompt management of an aortic dissection should it
      occur.

PMID- 27708701
TI  - The use of thrombolytic therapy in pregnancy.
AB  - The relative hypercoagulable state of pregnancy leads to an increased risk of
      thrombotic complications, of which some may be life-threatening or medically
      devastating. In the non-pregnant patient, the current guidelines suggest
      thrombolysis as the primary treatment in acute ischemic stroke, myocardial
      infarction when percutaneous intervention is unavailable, certain cases of
      mechanical valve thrombosis, and pulmonary embolism with hemodynamic compromise
      or shock. Given that clinical trial data regarding thrombolytic use in pregnant
      women are absent due to exclusion, the goal of this review is to summarize the
      available published data regarding the use of thrombolytic agents and subsequent
      outcomes and complications in pregnant women. Overall, the use of thrombolytic
      agents in pregnancy is associated with a relatively low reported complication
      rate, especially given the severe medical conditions for which they are
      indicated. The data would suggest that thrombolysis should be considered for
      appropriate indications similar to that of non-pregnant patients. However,
      caution should be exercised when drawing conclusions regarding maternal and fetal
      safety, given the lack of controlled clinical trials including pregnant women and
      the nature of the weak evidence level of the cumulative data presented in this
      review.

PMID- 27708704
TI  - Diagnostic effectiveness of 75 g oral glucose tolerance test for gestational
      diabetes in India based on the International Association of the Diabetes and
      Pregnancy Study Groups guidelines.
AB  - BACKGROUND: To determine the diagnostic effectiveness of the fasting and one-hour
      plasma glucose levels for gestational diabetes (GDM) based on International
      Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria.
      METHODS: A Cross-sectional study that included 2348 pregnant women booked for
      antenatal care in 2011 at a tertiary care perinatal institute. Pregnant women
      underwent a 75 g oral glucose tolerance test (OGTT) between 24 and 28 weeks of
      gestation. Outcome measures include the incidence of GDM based on the IADPSG
      criteria and the diagnostic effectiveness of the recommended fasting and one-hour
      plasma glucose cut-off if used in isolation. RESULTS: The incidence of GDM was
      21.81% (n = 520, 95% CI: 20.15, 23.57) with the IADPSG criteria. A fasting plasma
      glucose cut-off 92 mg/dL, in isolation, correctly classified 87.16% of GDM, with
      a specificity of 96.08%, clinically significant positive likelihood ratio (14.08)
      and a post-test probability of 79.71%. The one-hour 75 g test, in isolation,
      correctly classified 85.74% of GDM, had specificity of 99.68% and clinically
      significant positive likelihood ratio (111.12) and post-test probability of
      96.87%. The application of the World Health Organization criteria would
      misclassify 11.91% (95% CI: 10.66, 13.26) of GDM as normal. CONCLUSIONS:
      Additional testing of plasma glucose levels can be avoided for 18.25% (n = 435,
      95% CI: 16.73, 19.84) if the IADPSG diagnostic criteria for GDM are applied with
      exit on a positive fasting or one-hour test result.

PMID- 27708703
TI  - Evaluation of home testing to improve follow up after gestational diabetes
      (Fingerstick Assessments of Sugar Two-months postpartum or FAST).
AB  - OBJECTIVE: Historically the rates of postpartum glucose tolerance testing for
      women with gestational diabetes (GDM) average a suboptimal 33%. Barriers include
      the need for new mothers to miss work and/or arrange for childcare in order to
      engage in a two-hour test at a commercial lab. This pilot study was initiated to
      test the theory that a home testing regimen would be accepted by patients and
      increase the rate of postpartum glucose assessments relative to published rates,
      without requiring additional health-care staff or resources to achieve this goal.
      STUDY DESIGN: Six weeks postpartum, women with GDM from an academic private
      practice were asked to check fingerstick blood glucose (FAST Protocol) four times
      a day for two days, and then obtain an oral glucose tolerance test (OGTT). The
      physician consultants saw the women each month during pregnancy and arranged the
      postpartum testing. RESULTS: Two of 69 refused to be consented. Twelve of the
      remaining 67(18%) women completed both the FAST regimen and the OGTT, three
      completed only the OGTT and five completed only the FAST regimen for a final
      follow-up rate of 20/67 (30%). The demands of caring for a newborn, or the
      annoyance of fingersticks, were barriers to compliance. CONCLUSIONS: In spite of
      intense physician involvement, this home testing regimen was not associated with
      an increase in the rates of women participating in postpartum glucose
      assessments.

PMID- 27708705
TI  - Beware of delayed severe brain swelling after intracerebral haematoma in HELLP
      syndrome.
AB  - Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a
      condition associated with increased risk of adverse outcomes during pregnancy and
      peripartum, including neurological complications. We report the third case in the
      world literature of delayed brain swelling following cerebral haemorrhage as a
      complication of HELLP syndrome. A 36-year-old woman in labour developed HELLP,
      which was complicated with intracerebral haematoma. This was evacuated, but motor
      impairment persisted after surgery and unfortunately the patient died
      unexpectedly during the 11th postoperative day. Computer tomographic brain scans
      documented diffuse cerebral swelling, which we think may have been caused by
      cerebral vasospasm. Cerebral vasospasm should always be considered when managing
      patients who suffered from stroke complicating HELLP syndrome. Close monitoring
      is advised even in later stages of recovery.

PMID- 27708706
TI  - Bell's palsy in pregnancy: underlying HELLP syndrome or pre-eclampsia?
AB  - Bell's palsy is not uncommon during pregnancy. An association with pre-eclampsia
      (PE) has been reported previously. Furthermore, it has even been suggested that
      Bell's palsy could be a predictor of PE. We report three cases illustrating
      various possible aspects of this association, one of them including the features
      of HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome.

PMID- 27708707
TI  - Rare case of combined factor V and factor X deficiency in pregnancy: presenting
      as secondary postpartum haemorrhage in first pregnancy and successful outcome in
      second pregnancy.
AB  - Isolated factor V and factor X deficiency is a very rare condition affecting 1 in
      500,000-1,000,000 persons worldwide. We present a rare first reported case of
      combined deficiency of factor V and factor X where the patient developed
      secondary postpartum haemorrhage in first pregnancy, after which she was
      diagnosed to have this rare disorder and her subsequent pregnancy was then
      successfully managed.

PMID- 27708708
TI  - A case of recurrent severe pre-eclampsia associated with essential
      cryofibrinogenaemia.
AB  - Essential cryofibrinogenaemia is a rare disorder characterized by cryofibrinogens
      without cryoglobulins. Connective tissue disorders and thrombophilia are known to
      increase risk of pre-eclampsia, but pre-eclampsia has not previously been
      reported in association with cryofibrinogenaemia. We report the case of a 32-year
      old woman with recurrent severe pre-eclampsia diagnosed with essential
      cryofibrinogenaemia.

PMID- 27708709
TI  - Severe metabolic alkalosis in pregnancy.
AB  - Metabolic alkalosis is uncommon in pregnancy and is most often the result of
      severe vomiting. If this is present at the time of delivery, transient metabolic
      derangement in the fetus can occur, potentially requiring additional organ
      support. A 22-year-old woman is described, who presented at 37 weeks gestation
      with a severe metabolic alkalosis, vomiting and acute renal and hepatic
      impairment. The investigations, management options and maternal and fetal outcome
      are described.

PMID- 27708711
TI  - Identification and characterization of putative xylose and cellobiose
      transporters in Aspergillus nidulans.
AB  - BACKGROUND: The conversion of lignocellulosic biomass to biofuels (second
      generation biofuel production) is an environmentally friendlier alternative to
      petroleum-based energy sources. Enzymatic deconstruction of lignocellulose,
      catalyzed by filamentous fungi such as Aspergillus nidulans, releases a mixture
      of mono- and polysaccharides, including hexose (glucose) and pentose (xylose)
      sugars, cellodextrins (cellobiose), and xylooligosaccharides (xylobiose). These
      sugars can subsequently be fermented by yeast cells to ethanol. One of the major
      drawbacks in this process lies in the inability of yeast, such as Saccharomyces
      cerevisiae, to successfully internalize sugars other than glucose. The aim of
      this study was, therefore, to screen the genome of A. nidulans, which encodes a
      multitude of sugar transporters, for transporters able to internalize non-glucose
      sugars and characterize them when introduced into S. cerevisiae. RESULTS: This
      work identified two proteins in A. nidulans, CltA and CltB, with roles in
      cellobiose transport and cellulose signaling, respectively. CltA, when introduced
      into S. cerevisiae, conferred growth on low and high concentrations of
      cellobiose. Deletion of cltB resulted in reduced growth and extracellular
      cellulase activity in A. nidulans in the presence of cellobiose. CltB, when
      introduced into S. cerevisiae, was not able to confer growth on cellobiose,
      suggesting that this protein is a sensor rather than a transporter. However, we
      have shown that the introduction of additional functional copies of CltB
      increases the growth in the presence of low concentrations of cellobiose,
      strongly indicating CltB is able to transport cellobiose. Furthermore, a
      previously identified glucose transporter, HxtB, was also found to be a major
      xylose transporter in A. nidulans. In S. cerevisiae, HxtB conferred growth on
      xylose which was accompanied by ethanol production. CONCLUSIONS: This work
      identified a cellobiose transporter, a xylose transporter, and a putative
      cellulose transceptor in A. nidulans. This is the first time that a sensor role
      for a protein in A. nidulans has been proposed. Both transporters are also able
      to transport glucose, highlighting the preference of A. nidulans for this carbon
      source. This work provides a basis for future studies which aim at characterizing
      and/or genetically engineering Aspergillus spp. transporters, which, in addition
      to glucose, can also internalize other carbon sources, to improve transport and
      fermentation of non-glucose sugars in S. cerevisiae.

PMID- 27708712
TI  - One pedigree we all may have come from - did Adam and Eve have the chromosome 2
      fusion?
AB  - BACKGROUND: In contrast to Great Apes, who have 48 chromosomes, modern humans and
      likely Neandertals and Denisovans have and had, respectively, 46 chromosomes. The
      reduction in chromosome number was caused by the head-to-head fusion of two
      ancestral chromosomes to form human chromosome 2 (HSA2) and may have contributed
      to the reproductive barrier with Great Apes. RESULTS: Next generation sequencing
      and molecular clock analyses estimated that this fusion arose prior to our last
      common ancestor with Neandertal and Denisovan hominins ~ 0.74 - 4.5 million years
      ago. HYPOTHESES: I propose that, unlike recurrent Robertsonian translocations in
      humans, the HSA2 fusion was a single nonrecurrent event that spread through a
      small polygamous clan population bottleneck. Its heterozygous to homozygous
      conversion, fixation, and accumulation in the succeeding populations was likely
      facilitated by an evolutionary advantage through the genomic loss rather than
      deregulation of expression of the gene(s) flanking the HSA2 fusion site at 2q13.
      CONCLUSIONS: The origin of HSA2 might have been a critical evolutionary event
      influencing higher cognitive functions in various early subspecies of hominins.
      Next generation sequencing of Homo heidelbergensis and Homo erectus genomes and
      complete reconstruction of DNA sequence of the orthologous subtelomeric
      chromosomes in Great Apes should enable more precise timing of HSA2 formation and
      better understanding of its evolutionary consequences.

PMID- 27708713
TI  - New insights of karyoevolution in the Amazonian turtles Podocnemis expansa and
      Podocnemis unifilis (Testudines, Podocnemidae).
AB  - BACKGROUND: Cytogenetic studies were conducted in the Brazilian Amazon turtles,
      Podocnemis expansa Schweigger, 1912 (PEX) and Podocnemis unifilis Troschel, 1848
      (PUN) to understand their karyoevolution. Their chromosomal complements were
      compared using banding techniques (C, G-, Ag-NOR and Chromomycin A3) and
      fluorescence in situ hybridization (FISH), and efforts were made to establish
      evolutionary chromosomal relationships within the Podocnemidae family. RESULTS:
      Our results revealed that both species have a chromosome complement of 2n = 28.
      For PEX and PUN, the fundamental numbers (FNs) were 54 and 52, respectively and
      the karyotypic formulas (KFs) were 24 m/sm + 2st + 2a and 22 m/sm + 2st + 4a,
      respectively. G-banding evidenced homologies between the two species and allowed
      identify a heteromorphic pair (chromosome pair 10) in PUN. In PEX, constitutive
      heterochromatin (CH) was found in the centromeric regions of pairs 1, 2, 4, 6 and
      11 and on 9p. In PUN, CH was observed in the centromeric regions of all
      chromosomes, and in small proximal bands on 1p, 2p, 3q, 4q, 5q, 9q, 10q and 11q.
      Moreover, CH amplification was seen in one of the homologs of pair 10 (the
      heteromorphic pair). The CMA3 staining results were consistent with the CH
      findings. Ag-NOR staining showed that nucleolar organizing regions (NORs) were
      localized in the pericentromeric region of pair 1 in both species, and this
      result was confirmed by the 18S rDNA FISH probe. FISH with telomeric probes
      identified telomeric sequences in the distal regions of all chromosomes. In
      addition, interstitial telomeric sequences (ITSs) were present in seven
      chromosome pairs of PUN, perhaps reflecting the amplification of telomere-like
      sequences. FISH with a probe against the transposable element (TE), Rex 6,
      revealed that it is dispersed in euchromatic regions of the first chromosome
      pairs of both species. This is the first report describing the FISH-based
      analysis of PEX and PUN for the 18S rDNA, Rex 6 and human telomeric sequences.
      CONCLUSIONS: Our results contribute to clarifying the chromosomal homologies and
      rearrangement mechanisms that occurred during the evolution of these species, and
      may help researchers uncover new markers that will improve our understanding of
      the taxonomy and systematic classification of Podocnemidae. TRIAL REGISTRATION:
      ISRCTN ISRCTN73824458. Registered 28 September 2014. Retrospectively registered.

PMID- 27708714
TI  - The presence of two rare genomic syndromes, 1q21 deletion and Xq28 duplication,
      segregating independently in a family with intellectual disability.
AB  - BACKGROUND: 1q21 microdeletion syndrome is a rare contiguous gene deletion
      disorder with de novo or autosomal dominant inheritance patterns and its
      phenotypic features include intellectual disability, distinctive facial
      dysmorphism, microcephaly, cardiac abnormalities, and cataracts. MECP2
      duplication syndrome is an X-linked recessive neurodevelopmental disorder
      characterized by intellectual disability, global developmental delay, and other
      neurological complications including late-onset seizures. Previously, these two
      different genetic syndromes have not been reported segregating independently in a
      same family. CASE PRESENTATION: Here we describe two siblings carrying either a
      chromosome 1q21 microdeletion or a chromosome Xq28 duplication. Using a
      comparative genomic hybridization (CGH) array, we identified a 1.24 Mb
      heterozygous deletion at 1q21 resulting in the loss of 9 genes in a girl with
      learning disability, hypothyroidism, short stature, sensory integration disorder,
      and soft dysmorphic features including cupped ears and a unilateral ear pit. We
      also characterized a 508 kb Xq28 duplication encompassing MECP2 in her younger
      brother with hypotonia, poor speech, cognitive and motor impairment. The parental
      CGH and quantitative PCR (qPCR) analyses revealed that the 1q21 deletion in the
      elder sister is de novo, but the Xq28 duplication in the younger brother was
      originally inherited from the maternal grandmother through the mother, both of
      whom are asymptomatic carriers. RT-qPCR assays revealed that the affected brother
      has almost double the amount of MECP2 mRNA expression compared to other family
      members of both genders including maternal grandmother and mother who have the
      same Xq28 duplication with no phenotype. This suggests the X chromosome with an
      Xq28 duplication in the carrier females is preferentially silenced. CONCLUSION:
      From our understanding, this would be the first report showing the independent
      segregation of two genetically unrelated syndromes, 1q21 microdeletion and Xq28
      duplication, in a same family, especially in siblings. Although these two
      chromosomal abnormalities share some similar phenotypes such as intellectual
      disability, mild dysmorphic features, and cardiac abnormalities, the presence of
      two unrelated and rare syndromes in siblings is very unusual. Therefore, further
      comprehensive investigations in similar cases are required for future studies.

PMID- 27708715
TI  - 12p deletion spectrum syndrome: a new case report reinforces the evidence
      regarding the potential relationship to autism spectrum disorder and related
      developmental impairments.
AB  - BACKGROUND: Autism Spectrum Disorders (ASD) now encompass a broad heterogeneous
      group of people who present in the early developmental years with a wide range of
      social and communication deficits, which are typically also associated with
      complex repetitive behaviors and circumscribed interests. The target goal is to
      heighten readers' perception into the trend to personalize the distinct autistic
      and related developmental conditions encompassing the 12p region. CASE
      PRESENTATION: This is a case-report of a 4-year-old male who presented the core
      signs of ASD, which were thought to be related to a rare 12p13.2 deletion.  We
      further reviewed the literature in order to outline the related developmental
      conditions in the 12p region. Aside from this patient reported here, we found an
      additional number of 43 cases described in the medical literature since 1974,
      that have been related to deletions in the 12p region. However, to the best of
      our knowledge, none of the previous had been specifically linked to the 12p13.2
      band. CONCLUSIONS: The 12p deletion spectrum is rarely described as part of the
      selective genotypes thought to be related to ASD. Even inside of a small piece of
      the puzzle, there might be ample variation in the behavioral and clinical
      phenotypes of children and adults presenting with this particular genetic
      profile. In that regard, the particular 12p13.2 distal deletion presentation is
      one of the possible genotypes encompassed by the "12p deletion spectrum
      syndrome", that might be potentially connected to the diagnosis of ASD and
      related developmental disorders.

PMID- 27708716
TI  - Erratum to: Delineation variable genotype/phenotype correlations of 6q27 terminal
      deletion derived from dic(6;18)(q27;p10).
AB  - [This corrects the article DOI: 10.1186/s13039-014-0078-3.].

PMID- 27708717
TI  - EpiMINE, a computational program for mining epigenomic data.
AB  - BACKGROUND: In epigenetic research, both the increasing ease of high-throughput
      sequencing and a greater interest in genome-wide studies have resulted in an
      exponential flooding of epigenetic-related data in public domain. This creates an
      opportunity for exploring data outside the limits of any specific query-centred
      study. Such data have to undergo standard primary analyses that are accessible
      with multiple well-stabilized programs. Further downstream analyses, such as
      genome-wide comparative, correlative and quantitative analyses, are critical in
      deciphering key biological features. However, these analyses are only accessible
      for computational researchers and completely lack platforms capable of handling,
      analysing and linking multiple interdisciplinary datasets with efficient
      analytical methods. RESULTS: Here, we present EpiMINE, a program for mining
      epigenomic data. It is a user-friendly, stand-alone computational program
      designed to support multiple datasets, for performing genome-wide correlative and
      quantitative analysis of ChIP-seq and RNA-seq data. Using data available from the
      ENCODE project, we illustrated several features of EpiMINE through different
      biological scenarios to show how easy some known observations can be verified.
      These results highlight how these approaches can be helpful in identifying novel
      biological features. CONCLUSIONS: EpiMINE performs different kinds of genome-wide
      quantitative and correlative analyses, using ChIP-seq- and RNA-seq-related
      datasets. Its framework enables it to be used by both experimental and
      computational researchers. EpiMINE can be downloaded from
      https://sourceforge.net/projects/epimine/.

PMID- 27708718
TI  - A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth
      potency for effective treatment of Crohn's disease associated with Mycobacterium
      avium subspecies paratuberculosis.
AB  - BACKGROUND: Most recently we reported that RHB-104 triple antibiotics combination
      in culture is bactericidal and should be effective for treatment of Crohn's
      disease (CD)-associated with Mycobacterium avium subspecies paratuberculosis
      (MAP) (Alcedo et al. in Gut Pathog 14:32, 2016). The combination exhibited unique
      synergistic antimicrobial growth activity. The proprietary RHB-104 capsule
      formulation contains active ingredients (63.3 % Clarithromycin (CLA), 6.7 %
      Clofazimine (CLO) and 30 % Rifabutin (RIF)). In our earlier study, we could not
      dissolve the proprietary RHB-104 capsule formulation in one compatible solvent.
      Consequently, we re-created RHB-104 analog by adding appropriate concentrations
      of each of the three antibiotics into the cultures. The Minimum inhibitory
      concentration (MIC) for RHB-104 analog, CLA, CLO, RIF, CLA-CLO, CLA-RIF, CLO-RIF
      and their individual solvents were reported earlier (Alcedo et al. in Gut Pathog
      14:32, 2016). In this study, we succeeded in dissolving the proprietary RHB-104
      capsule formulation in a single proprietary solvent. This study is designed to
      compare of the MIC the proprietary RHB-104 capsule formulation to RHB-104 analog
      against MAP and other microorganisms. METHODS: BD BactecTM MGITTM Para-TB medium
      (Sparks, MD) system was used to determine the MIC of the proprietary RHB-104
      capsule formulation and RHB-104 analog and their solvents against MAP and several
      other microorganisms. The final concentration of solvents used to dissolve all
      the drugs were <=0.5 % (v/v). RESULTS: The MIC for the RHB-104 proprietary
      solvent against MAP was consistent against all microorganisms tested in the study
      at 12.5 % (v/v). The MIC for the proprietary RHB-104 capsule formulation was
      similar to RHB-104 analog against several MAP clinical strains with MIC <= 0.2
      MUg/mL. The MIC for the proprietary RHB-104 capsule formulation was at 2.0 MUg/mL
      against MAP strain MS 137 and M. avium strain JF7 compared to 4.0 ug/mL for RHB
      104 analog. Similarly, the MIC of RHB-104 formulation capsule was significantly
      lower than RHB-104 analog against M. tuberculosis HR237, M. fortuitism subspecies
      fortuitum, M. smegmatis ATCC 27199, Staphylococcus aureus ATCC 25923 and Listeria
      monocytogenes ATCC 19112. CONCLUSION: The data demonstrated that the proprietary
      RHB-104 capsule formulation is more potent in culture against Mycobacteria and
      other microorganisms especially those with MIC >0.2. Formulation of multi-drugs
      in a single capsule results in potent synergistic anti-microbial activity far
      exceeds treatment the culture with multi-individually dissolved drugs. RHB-104
      capsule formulation should be more effective to eradicate MAP infection in
      patients with CD. The study provides evidence that combining weak antibiotics in
      one formulation might be the new silver bullet to combat bacteria.

PMID- 27708719
TI  - Th17 cells in Type 1 diabetes: a future perspective.

PMID- 27708720
TI  - Reaching Those Most in Need - A Call to Action for Advanced Parkinson's Disease.
AB  - Much of the clinical and research attention for Parkinson's Disease (PD) has
      focused on mild to moderate stages. As the disease advances, it can become
      difficult for patients to attend clinical visits. These patients are often lost
      to follow-up, and consequently, vanish from the pool of potential research
      subjects who could inform our management of this understudied population. We aim
      to increase awareness about this population and potential interventions to
      improve continuity of care and foster research in advanced PD.

PMID- 27708721
TI  - The impact of MTHFR 677C -> T risk knowledge on changes in folate intake:
      findings from the Food4Me study.
AB  - BACKGROUND: It is hypothesised that individuals with knowledge of their genetic
      risk are more likely to make health-promoting dietary and lifestyle changes. The
      present study aims to test this hypothesis using data from the Food4Me study.
      This was a 6-month Internet-based randomised controlled trial conducted across
      seven centres in Europe where individuals received either general healthy eating
      advice or varying levels of personalised nutrition advice. Participants who
      received genotype-based personalised advice were informed whether they had the
      risk (CT/TT) (n = 178) or non-risk (CC) (n = 141) alleles of the
      methylenetetrahydrofolate reductase (MTHFR) gene in relation to cardiovascular
      health and the importance of a sufficient intake of folate. General linear model
      analysis was used to assess changes in folate intake between the MTHFR risk,
      MTHFR non-risk and control groups from baseline to month 6 of the intervention.
      RESULTS: There were no differences between the groups for age, gender or BMI.
      However, there was a significant difference in country distribution between the
      groups (p = 0.010). Baseline folate intakes were 412 +/- 172, 391 +/- 190 and 410
      +/- 186 MUg per 10 MJ for the risk, non-risk and control groups, respectively.
      There were no significant differences between the three groups in terms of
      changes in folate intakes from baseline to month 6. Similarly, there were no
      changes in reported intake of food groups high in folate. CONCLUSIONS: These
      results suggest that knowledge of MTHFR 677C -> T genotype did not improve folate
      intake in participants with the risk variant compared with those with the non
      risk variant. TRIAL REGISTRATION: ClinicalTrials.gov NCT01530139.

PMID- 27708724
TI  - Retraction Notice: Research on the Effect of Puerarin on Alleviating Sports
      Fatigue.

PMID- 27708723
TI  - Computational Methods Applied to Rational Drug Design.
AB  - Due to the synergic relationship between medical chemistry, bioinformatics and
      molecular simulation, the development of new accurate computational tools for
      small molecules drug design has been rising over the last years. The main result
      is the increased number of publications where computational techniques such as
      molecular docking, de novo design as well as virtual screening have been used to
      estimate the binding mode, site and energy of novel small molecules. In this work
      I review some tools, which enable the study of biological systems at the
      atomistic level, providing relevant information and thereby, enhancing the
      process of rational drug design.

PMID- 27708722
TI  - PITX3 promoter methylation is a prognostic biomarker for biochemical recurrence
      free survival in prostate cancer patients after radical prostatectomy.
AB  - BACKGROUND: Molecular biomarkers that might help to distinguish between more
      aggressive and clinically insignificant prostate cancers (PCa) are still urgently
      needed. Aberrant DNA methylation as a common molecular alteration in PCa seems to
      be a promising source for such biomarkers. In this study, PITX3 DNA methylation
      (mPITX3) and its potential role as a prognostic biomarker were investigated.
      Furthermore, mPITX3 was analyzed in combination with the established PCa
      methylation biomarker PITX2 (mPITX2). METHODS: mPITX3 and mPITX2 were assessed by
      a quantitative real-time PCR and by means of the Infinium HumanMethylation450
      BeadChip. BeadChip data were obtained from The Cancer Genome Atlas (TCGA)
      Research Network. DNA methylation differences between normal adjacent, benign
      hyperplastic, and carcinomatous prostate tissues were examined in the TCGA
      dataset as well as in prostatectomy specimens from the University Hospital Bonn.
      Retrospective analyses of biochemical recurrence (BCR) were conducted in a
      training cohort (n = 498) from the TCGA and an independent validation cohort (n =
      300) from the University Hospital Bonn. All patients received radical
      prostatectomy. RESULTS: In PCa tissue, mPITX3 was increased significantly
      compared to normal and benign hyperplastic tissue. In univariate Cox proportional
      hazards analyses, mPITX3 showed a significant prognostic value for BCR (training
      cohort: hazard ratio (HR) = 1.83 (95 % CI 1.07-3.11), p = 0.027; validation
      cohort: HR = 2.56 (95 % CI 1.44-4.54), p = 0.001). A combined evaluation with
      PITX2 methylation further revealed that hypermethylation of a single PITX gene
      member (either PITX2 or PITX3) identifies an intermediate risk group.
      CONCLUSIONS: PITX3 DNA methylation alone and in combination with PITX2 is a
      promising biomarker for the risk stratification of PCa patients and adds relevant
      prognostic information to common clinically implemented parameters. Further
      studies are required to determine whether the results are transferable to a
      biopsy-based patient cohort. Trial registration: Patients for this unregistered
      study were enrolled retrospectively.

PMID- 27708725
TI  - Influence of Enamel Thickness on Bleaching Efficacy: An In-Depth Color Analysis.
AB  - This study evaluated the influence of different enamel thicknesses and bleaching
      agents on treatment efficacy in-depth by spectrophotometry color analysis. Eighty
      bovine dental fragments were previously stained in black tea solution and
      randomly assigned into eight groups (n=10), 1.75mm dentin thickness and different
      enamel thicknesses as follows: 0.5mm, 1.0mm planned, 1.0mm unplanned (aprismatic
      enamel), and absence of enamel. The 10% carbamide peroxide (CP) and 35% hydrogen
      peroxide (HP) bleaching gels were applied on the enamel surface following the
      manufacturer's recommendations. Color of underlying dentin was evaluated at four
      times: after staining with tea (baseline) and after each one of the three weeks
      of bleaching treatment, by CIE L*a*b* system using reflectance spectrophotometer
      (CM 700d, Konica Minolta). The DeltaE, DeltaL, Deltaa, and Deltab values were
      recorded and subjected to repeated measures ANOVA and Tukey's test (alpha=0.05).
      The results showed an increase on lightness (L*), with decreased redness (a*) and
      yellowness (b*). At first and second week, bleaching with CP showed higher
      whitening effectiveness compared to bleaching with HP and the presence of
      aprismatic enamel significantly reduced DeltaE for bleaching with CP. After three
      weeks of bleaching, few differences were observed between CP and HP groups, and
      outer enamel layer caused no influence on bleaching effectiveness. Overall, both
      at-home and in-office bleaching treatments were effective and the presence of
      aprismatic enamel did not interfere on the whitening efficacy.

PMID- 27708726
TI  - Bisphenol A Release: Survey of the Composition of Dental Composite Resins.
AB  - BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor with potential toxicity.
      Composite resins may not contain pure BPA, but its derivatives are widely used.
      Several studies found doses of BPA or its derivatives in saliva or urine of
      patients after composite resin placement. OBJECTIVE: The aims of this study were
      to establish an exhaustive list of composite resins marketed in Europe and their
      composition, and to assess the extent of BPA derivatives used. METHODS: A
      research on manufacturers' websites was performed to reference all composite
      resins marketed in Europe, then their composition was determined from both
      material safety data sheets and a standardized questionnaire sent to
      manufacturers. Manufacturers had to indicate whether their product contained the
      monomers listed, add other monomers if necessary, or indicate "not disclosed".
      RESULTS: 160 composite resins were identified from 31 manufacturers and 23
      manufacturers (74.2%) responded to the survey. From the survey and websites, the
      composition of 130 composite resins (81.2%) was: 112 (86.2%) based on BPA
      derivatives, 97 (74.7%) on bis-GMA, 17 (13.1%) without monomer derived from BPA
      (UDMA, sometimes with TEGDMA) and 6 (4.6%) with UDMA (only); 1 (0.8%) did not
      contain a BPA derivative or UDMA or TEGDMA. Pure BPA was never reported.
      CONCLUSION: This work has established a list of 18 composite resins that contain
      no BPA derivative. Manufacturers should be required to report the exact
      composition of their products as it often remains unclear or incomplete.

PMID- 27708727
TI  - Masseter Muscle Activity in Track and Field Athletes: A Pilot Study.
AB  - Teeth clenching has been shown to improve remote muscle activity (by augmentation
      of the Hoffmann reflex), and joint fixation (by decreased reciprocal inhibition)
      in the entire body. Clenching could help maintain balance, improve systemic
      function, and enhance safety. Teeth clenching from a sports dentistry viewpoint
      was thought to be important and challenging. Therefore, it is quite important to
      investigate mastication muscles' activity and function during sports events for
      clarifying a physiological role of the mastication muscle itself and involvement
      of mastication muscle function in whole body movement. Running is a basic motion
      of a lot of sports; however, a mastication muscles activity during this motion
      was not clarified. Throwing and jumping operation were in a same situation. The
      purpose of this study was to investigate the presence or absence of masseter
      muscle activity during track and field events. In total, 28 track and field
      athletes took part in the study. The Multichannel Telemetry system was used to
      monitor muscle activity, and the electromyograms obtained were synchronized with
      digital video imaging. The masseter muscle activity threshold was set 15% of
      maximum voluntary clenching. As results, with few exceptions, masseter muscle
      activity were observed during all analyzed phases of the 5 activities, and that
      phases in which most participants showed masseter muscle activity were
      characterized by initial acceleration, such as in the short sprint, from the
      commencement of throwing to release in both the javelin throw and shot put, and
      at the take-off and landing phases in both jumps.

PMID- 27708729
TI  - Current Treatment Options for Rotator Cuff Tears.

PMID- 27708728
TI  - Hepatitis B Serology in Patients with Rheumatic Diseases.
AB  - BACKGROUND: Only limited data are available on the prevalence of hepatitis B in
      patients with proven rheumatic diseases and thus the risk of reactivation under
      immunosuppressive therapy. OBJECTIVE: To analyse hepatitis B serology in patients
      with rheumatic diseases prior to therapy. METHOD: In total, 1,338 patient records
      were analysed for HBsAg, HBsAb and HBcAb in a cross-sectional, single-centre
      study between 2011 and 2015 at first presentation. Data acquisition was realized
      using electronic patient files created during routine care. The main variables
      considered as predictors for HBV reactivation included (i) the exact type of
      rheumatic disease and (ii) the therapeutically induced immunosuppression.
      RESULTS: Overall, 5.9% of patients (n=79) had proven contact with hepatitis B
      (HBcAb positive), and HBsAb were not detected in 1.3% (n=18). The rate of
      vaccinated subjects was 7.8%. HBsAg was detected in 3 patients (0.2%). In
      addition, 70.3% of patients were treated during the course of rheumatologic
      disease previously or currently with glucocorticoids, 85.2% with disease
      modifying anti-rheumatic drugs (DMARDs) and 20.1% with a biologic agent ( e.g. ,
      anti-IL-6, anti-TNFalpha, anti-CD20, CTLA4Ig or anti-IL-12/23). CONCLUSION:
      Prevalence of hepatitis B serostatus in the analysed rheumatic patients regarding
      HBs-Ag and HBcAb with or without HBsAb prior to therapy does not differ from the
      data published for the general population in Germany. However, the rate of
      hepatitis B vaccinated patients was lower. In general, a significant portion of
      patients (5.9%) has been exposed to HBV and therefore exhibited an increased risk
      of reactivation of hepatitis B when undergoing immunosuppressive therapy.

PMID- 27708730
TI  - Irreparable Rotator Cuff Tears: Restoring Joint Kinematics by Tendon Transfers.
AB  - BACKGROUND: Tendon transfers can be a surgical treatment option in managing
      younger, active patients with massive irreparable rotator cuff tears. The purpose
      of this article is to provide an overview of the use of tendon transfers to treat
      massive irreparable rotator cuff tears and to summarize clinical outcomes.
      METHODS: A selective literature search was performed and personal surgical
      experiences are reported. RESULTS: Latissimus dorsi transfers have been used for
      many years in the management of posterosuperior rotator cuff tears with good
      reported clinical outcomes. It can be transferred without or with the teres major
      (L'Episcopo technique). Many surgical techniques have been described for
      latissimus dorsi transfer including single incision, double incision, and
      arthroscopically assisted transfer. Transfer of the pectoralis major tendon is
      the most common tendon transfer procedure performed for anterosuperior rotator
      cuff deficiencies. Several surgical techniques have been described, however
      transfer of the pectoralis major beneath the coracoid process has been found to
      most closely replicate the force vector that is normally provided by the intact
      subscapularis. CONCLUSION: Tendon transfers can be used successfully in the
      management of younger patients with massive irreparable rotator cuff tears and
      minimal glenohumeral arthritis. Improvements in clinical outcomes scores and
      range of motion have been demonstrated. This can delay arthroplasty, which is of
      particular importance for younger patients with high functional demands.

PMID- 27708732
TI  - The Role of Platelet Rich Plasma (PRP) and Other Biologics for Rotator Cuff
      Repair.
AB  - BACKGROUND: Surgical treatment of rotator cuff tears has consistently
      demonstrated good clinical and functional outcomes. However, in some cases, the
      rotator cuff fails to heal. While improvements in rotator cuff constructs and
      biomechanics have been made, the role of biologics to aid healing is currently
      being investigated. METHODS: A selective literature search was performed and
      personal surgical experiences are reported. RESULTS: Biologic augmentation of
      rotator cuff repairs can for example be performed wtableith platelet-rich plasma
      (PRP) and mesenchymal stem cells (MSCs). Clinical results on PRP application have
      been controversial. Application of MSCs has shown promise in animal studies, but
      clinical data on its effectiveness is presently lacking. The role of Matrix
      Metalloproteinase (MMP) inhibitors is another interesting field for potential
      targeted drug therapy after rotator cuff repair. CONCLUSIONS: Large randomized
      clinical studies need to confirm the benefit of these approaches, in order to
      eventually lower retear rates and improve clinical outcomes after rotator cuff
      repair.

PMID- 27708731
TI  - Risk Factors, Pathobiomechanics and Physical Examination of Rotator Cuff Tears.
AB  - BACKGROUND: It is important to appreciate the risk factors for the development of
      rotator cuff tears and specific physical examination maneuvers. METHODS: A
      selective literature search was performed. RESULTS: Numerous well-designed
      studies have demonstrated that common risk factors include age, occupation, and
      anatomic considerations such as the critical shoulder angle. Recently, research
      has also reported a genetic component as well. The rotator cuff axially
      compresses the humeral head in the glenohumeral joint and provides rotational
      motion and abduction. Forces are grouped into coronal and axial force couples.
      Rotator cuff tears are thought to occur when the force couples become imbalanced.
      CONCLUSION: Physical examination is essential to determining whether a patient
      has an anterosuperior or posterosuperior tear. Diagnostic accuracy increases when
      combining a series of examination maneuvers.

PMID- 27708733
TI  - Patch-Augmented Rotator Cuff Repair and Superior Capsule Reconstruction.
AB  - BACKGROUND: Massive rotator cuff tears in active patients with minimal
      glenohumeral arthritis remain a particular challenge for the treating surgeon.
      METHODS: A selective literature search was performed and personal surgical
      experiences are reported. RESULTS: For patients with irreparable rotator cuff
      tears, a reverse shoulder arthroplasty or a tendon transfer are often performed.
      However, both procedures have rather high complication rates and debatable long
      term results, particularly in younger patients. Therefore, patch-augmented
      rotator cuff repair or superior capsule reconstruction (SCR) have been recently
      developed as arthroscopically applicable treatment options, with promising
      biomechanical and early clinical results. CONCLUSION: For younger patients with
      irreparable rotator cuff tears wishing to avoid tendon transfers or reverse total
      shoulder arthroplasty, both patch-augmentation and SCR represent treatment
      options that may delay the need for more invasive surgery.

PMID- 27708734
TI  - Arthroscopic Debridement for Irreparable Rotator Cuff Tears.
AB  - BACKGROUND: Arthroscopic debridement represents a salvage procedure for
      irreparable rotator cuff tears. It is important to accurately diagnose the
      patient for irreparable rotator cuff tears. The diagnosis and the therapeutic
      options must be explained to the patient. It is mandatory that the patient
      understands the primary goal of the arthroscopic debridement being reduction of
      pain, not improving strength or function. METHODS: The procedure consists of 7
      distinct steps to debride the soft tissues and alleviate pain. RESULTS: Even
      though there is a lack of evidence that this procedure is superior to other
      therapeutic options, it has shown good results in patients with the main
      complaint of pain. CONCLUSION: The results reported in some studies should,
      however, be interpreted with caution, taking into consideration the substantial
      structural damage in irreparable defects.

PMID- 27708735
TI  - Summary of Meta-Analyses Dealing with Single-Row versus Double-Row Repair
      Techniques for Rotator Cuff Tears.
AB  - BACKGROUND: Several meta-analyses of randomized clinical trials have been
      performed to analyze whether double-row (DR) rotator cuff repair (RCR) provides
      superior clinical outcomes and structural healing compared to single-row (SR)
      repair. The purpose of this study was to sum up the results of meta-analysis
      comparing SR and DR repair with respect on clinical outcomes and re-tear rates.
      METHODS: A literature search was undertaken to identify all meta-analyses dealing
      with randomized controlled trials comparing clinical und structural outcomes
      after SR versus DR RCR. RESULTS: Eight meta-analyses met the eligibility
      criteria: two including Level I studies only, five including both Level I and
      Level II studies, and one including additional Level III studies. Four meta
      analyses found no differences between SR and DR RCR for patient outcomes, whereas
      four favored DR RCR for tears greater than 3 cm. Two meta-analyses found no
      structural healing differences between SR and DR RCR, whereas six found DR repair
      to be superior for tears greater than 3 cm tears. CONCLUSION: No clinical
      differences are seen between single-row and double-row repair for small and
      medium rotator cuff tears after a short-term follow-up period with a higher re
      tear rate following single-row repairs. There seems to be a trend to superior
      results with double-row repair in large to massive tear sizes.

PMID- 27708736
TI  - Prognosis Driven Rehabilitation After Rotator Cuff Repair Surgery.
AB  - BACKGROUND: Rehabilitation after rotator cuff repair surgery has been the focus
      of several clinical trials in the past decade. Many illuminate new evidence with
      regard to the prognosis of structural and functional success after surgery.
      METHODS: A selective literature search was performed and personal
      physiotherapeutic and surgical experiences are reported. RESULTS: Post-operative
      rehabilitation parameters, namely the decision to delay or allow early range of
      motion after surgery, play a large role in the overall success after surgery.
      Using a prognosis driven rehabilitation program offers clinicians a means of
      prescribing optimal rehabilitation parameters while ensuring structural and
      functional success. This commentary aims to synthesize the evidence in a spectrum
      of prognostic factors to guide post-operative rehabilitation. CONCLUSION: The
      optimal rehabilitation program after rotator cuff repair surgery is debatable;
      therefore, we suggest using a spectrum of prognostic factors to determine a
      rehabilitation program suited to ensure structural and functional success,
      quickly and safely.

PMID- 27708737
TI  - Non-Operative Management of Rotator Cuff Tears.
AB  - BACKGROUND: The role of nonoperative management for rotator cuff tears remains a
      matter of debate. Clinical results reported in the literature mainly consist of
      level IV studies, oftentimes combining a mixed bag of tear sizes and
      configurations, and are contradictory to some extent. METHODS: A selective
      literature search was performed and personal surgical experiences are reported.
      RESULTS: Most studies show an overall success rate of around 75% for nonoperative
      treatment. However, the majority of studies also present a progression of tear
      size and fatty muscle infiltration over time, with however debatable clinical
      relevance for the patient. Suggested factors associated with progression of a
      rotator cuff tear are an age of 60 years or older, full-thickness tears, and
      fatty infiltration of the rotator cuff muscles at the time of initial diagnosis.
      CONCLUSION: Non-operative management is indicated for patients with lower
      functional demands and moderate symptoms, and/or of course for those refusing to
      have surgery. Close routinely monitoring regarding development of tear size
      should be performed, especially in patients that remain symptomatic during
      nonoperative treatment. To ensure judicious patient counseling, it has to be
      taken into account that 1) tears that are initially graded as reparable may
      become irreparable over time, and 2) results after secondary surgical therapy
      after failed nonoperative treatment are usually reported to be inferior to those
      who underwent primary tendon repair.

PMID- 27708738
TI  - Are We Economically Efficient Enough to Increase the Potential of in Vitro
      Proliferation of Osteoblasts by Means of Pharmacochemical Agents?
AB  - BACKGROUND: The aim of this study was to test the necessity of using expensive
      and unaccesible pharmacological-chemical agents in the proliferation of bone
      tissue cultures and in the induction of mineralized matrix formation to increase
      the osteogenic effect. METHODS: For this purpose, human primary cell cultures
      were prepared and then divided into two groups. Whereas the cells in group I were
      fed with an osteoblast stimulator medium containing Dulbecco's Modified Eagle
      Medium (DMEM) and beta-glycerophosphate, the cells in group II were fed with DMEM
      containing dexamethasone and 2-phospho-L-ascorbic acid trisodium salt. Both
      groups were evaluated in terms of viability, toxicity, and proliferation and then
      compared in terms of cell surface morphology through inverted light and
      environmental scanning electron microscopy. In addition to immunoflow cytometric
      analyses, the effects of alkaline phosphatase activities were evaluated using the
      spectrophotometric method to examine the osteoblastic activities. Costs were
      calculated in the currency of the European Union (Euros). The Tukey Honestly
      Significant Difference test was used to reach the statistical evaluation of the
      data after the analysis of variance. RESULTS: It was reported that the level of
      the alkaline phosphates was higher in group I compared to group II. It was
      observed that the surface morphology quality, the number of living cells, and
      proliferation were higher in group II and that the results were deemed
      statistically significant. CONCLUSION: It was found that the 2-phospho-L-ascorbic
      acid trisodium salt and dexamethasone mixture was as effective as the expensive
      commercial kits on the osteogenic effect on human primary bone tissue.

PMID- 27708739
TI  - Is Casting for Non-Displaced Simple Scaphoid Waist Fracture Effective? A CT Based
      Assessment of Union.
AB  - OBJECTIVE: The purpose of this study is to report the union rate and time to
      union for acute non-displaced scaphoid waist fractures treated with a short arm
      thumb spica cast. METHODS: A database was searched (2006-2013) to identify acute
      undisplaced scaphoid waist fractures. Cases that were not given a trial of
      casting were excluded (n=33). X-rays, CT scans and health records for each
      patient were reviewed to extract data. RESULTS: 172 patients met inclusion
      criteria. There were 138 males, 34 females, the mean age was 30 +/- 16 years. The
      union rate was 99.4% (1 nonunion/172 subjects). The mean time to union was
      approximately 7.5 weeks (53 +/- 37 days). Energy of injury, age or gender did not
      affect union rates or time to union. Cysts did not affect the union rate (p=0.73)
      but patients with cystic resorption along the fracture line required
      approximately 10 weeks for union (69 +/- 60 days) compared to 7 weeks (51 +/- 34
      days) for those without cysts (p=0.05). Diabetes did not affect the union rate
      (p=0.81) but was found to increase the risk of delayed union (p=0.05). There was
      a weak, but statistically significant correlation between the number of days
      before the fracture was casted and the length of time needed to achieve union
      (r=0.27, p=0.001). CONCLUSION: Non-displaced scaphoid waist fractures have a high
      healing rate with appropriate identification and immobilization. Follow-up CT
      scans to assess healing can identify union within a shorter time frame (~7 weeks)
      than previously reported in the literature.

PMID- 27708740
TI  - Tranexamic Acid in a Multimodal Blood Loss Prevention Protocol to Decrease Blood
      Loss in Revision Total Knee Arthroplasty: A Cohort Study.
AB  - PURPOSE: To clarify if blood loss and transfusion requirements can be decreased
      in revision knee surgery through a multimodal blood loss approach with tranexamic
      acid (TXA). PATIENTS AND METHODS: A retrospective study was designed in 87 knees
      (79 patients) that received a knee revision between 2007 and 2013. To avoid
      heterogeneity in the surgical technique, only revisions with one single implant
      system were included. A treatment series of 44 knees that received TXA and other
      techniques in a multimodal blood loss protocol was compared to a control series
      of 43 knees that received neither TXA nor the rest of the multimodal blood loss
      protocol. No differences in the complexity of surgeries or case severity were
      detected. RESULTS: A significant decrease was observed from 58% transfusion rate
      in the control group to 5% in the treated group. The postoperative haemoglobin
      drop was also significantly different. Although the use of a blood loss
      prevention approach including TXA was the most relevant factor in the transfusion
      risk (OR=15), longer surgical time also associated an increased risk of
      transfusion (OR=1.15). CONCLUSION: This study supports the use of a two-dose
      intravenous TXA under a multimodal blood loss prevention approach in revision
      knee replacement with significant reduction in the transfusion rate,
      postoperative blood loss and haemoglobin drop.

PMID- 27708741
TI  - The Rule of Histology in the Diagnosis of Periprosthetic Infection: Specific
      Granulocyte Counting Methods and New Immunohistologic Staining Techniques may
      Increase the Diagnostic Value.
AB  - OBJECTIVE: The current study investigates the diagnostic accuracy of the criteria
      described for frozen sections and whether modern leukocyte specific staining
      techniques including leukocyte peroxidase and Naphtol-AS-D-chloroacetate-esterase
      will improve the accuracy of the intra-operative histology. METHOD: 77 patients
      undergoing revision total hip and knee arthroplasty were included in this
      retrospective study. Patients were grouped into septic and aseptic based on
      intraoperative cultures. Tissue samples were analyzed utilizing the Mirra,
      Feldman, Lonner, Banit and Athanasou criteria. RESULTS: An experienced
      pathologist had a high specificity (96%), but rather low sensitivity (57%)
      diagnosing infection. By using the Banit-, Mirra-, or Athanasou-criteria the
      sensitivity is increased to 0.90. The Feldman- and Lonner-criteria have a lower
      sensitivity (0.48 and 0.38), however, an increased specificity of 0.96 and 0.98,
      respectively. The Banit cut off has the highest accuracy (86%). MPOX and NACE
      staining increased the sensitivity and accuracy up to 100% and 92% respectively.
      CONCLUSION: Banit's cut off is the most accurate histologic criteria to diagnose
      infection. Modern leukocyte specific staining techniques slightly improve the
      accuracy. The synovial fluid white blood cell count appears to be the most
      accurate intraoperative test.

PMID- 27708743
TI  - Nigrosphaerin A a new isochromene derivative from the endophytic fungus
      Nigrospora sphaerica.
AB  - Nigrosphaerin A, a new isochromene derivative (1), was isolated from the
      endophytic fungus Nigrospora sphaerica and chemically identified as 3-(3,4
      dihydroxyphenyl)-4,6,8-trihydroxy-1H-isochromen-1-one-6-O-beta-d-glucopyranoside.
      In addition nineteen known compounds (2-20) were isolated from the same fungus
      and chemically identified. Compounds (1-3, 5, and 7-16) were isolated for the
      first time from this fungus. In vitro antileukemic, antileishmanial, antifungal,
      antibacterial and antimalarial activities of (1-20) were examined. Compounds 5,
      7, 9 and 10 showed good antileukemic activity against HL60 cells with IC50 values
      of 0.03, 0.39, 0.2 and 0.4 MUg/mL, respectively and against K562 cells with IC50
      values of 0.35, 0.35, 0.49 and 0.01 MUg/mL, respectively. Compounds 3, 4 and 6
      showed moderate antileishmanial activity with IC50 values of 30.2, 26.4 and 36.4
      MUg/ml, respectively. Compound 7 showed moderate antifungal activity against
      Cryptococcus neoformans with IC50 value of 14.8 MUg/mL.

PMID- 27708744
TI  - Turning Electromyography Reports Upside Down: A Pilot Study Surveying Referring
      Providers.
AB  - Providers are expressing a desire for more efficient ways to retrieve relevant
      clinical data from the Electronic Health Record. In an effort to improve our
      Electromyography and Nerve Conduction Study reports, we surveyed referring
      providers on the effects of having the IMPRESSION at the start of the report. Our
      survey respondents felt that using this format for an Electromyography and Nerve
      Conduction Study report significantly improved the quality of the report while
      saving them time and/or mouse clicks when interpreting the report. Electro
      diagnosticians might consider using this format for their Electromyography and
      Nerve Conduction Study reports to improve referring provider satisfaction.

PMID- 27708745
TI  - Sex Differences in Gamma Band Functional Connectivity Between the Frontal Lobe
      and Cortical Areas During an Auditory Oddball Task, as Revealed by Imaginary
      Coherence Assessment.
AB  - We studied sex-related differences in gamma oscillation during an auditory
      oddball task, using magnetoencephalography and electroencephalography assessment
      of imaginary coherence (IC). We obtained a statistical source map of event
      related desynchronization (ERD) / event-related synchronization (ERS), and
      compared females and males regarding ERD / ERS. Based on the results, we chose
      respectively seed regions for IC determinations in low (30-50 Hz), mid (50-100
      Hz) and high gamma (100-150 Hz) bands. In males, ERD was increased in the left
      posterior cingulate cortex (CGp) at 500 ms in the low gamma band, and in the
      right caudal anterior cingulate cortex (cACC) at 125 ms in the mid-gamma band.
      ERS was increased in the left rostral anterior cingulate cortex (rACC) at 375 ms
      in the high gamma band. We chose the CGp, cACC and rACC as seeds, and examined IC
      between the seed and certain target regions using the IC map. IC changes depended
      on the height of the gamma frequency and the time window in the gamma band.
      Although IC in the mid and high gamma bands did not show sex-specific
      differences, IC at 30-50 Hz in males was increased between the left rACC and the
      frontal, orbitofrontal, inferior temporal and fusiform target regions. Increased
      IC in males suggested that males may acomplish the task constructively,
      analysingly, emotionally, and by perfoming analysis, and that information
      processing was more complicated in the cortico-cortical circuit. On the other
      hand, females showed few differences in IC. Females planned the task with general
      attention and economical well-balanced processing, which was explained by the
      higher overall functional cortical connectivity. CGp, cACC and rACC were involved
      in sex differences in information processing and were likely related to
      differences in neuroanatomy, hormones and neurotransmitter systems.

PMID- 27708746
TI  - Associations and Trends in Cause-Specific Rates of Death Among Persons Reported
      with HIV Infection, 23 U.S. Jurisdictions, Through 2011.
AB  - BACKGROUND: Published death rates for persons with HIV have not distinguished
      deaths due to HIV from deaths due to other causes. Cause-specific death rates
      would allow better assessment of care needs. METHODS: Using data reported to the
      US national HIV surveillance system, we examined a) associations between selected
      decedent characteristics and causes of death during 2007-2011, b) trends in rates
      of death due to underlying causes among persons with AIDS during 1990-2011, and
      among all persons with diagnosed HIV infection (with or without AIDS) during 2000
      2011. RESULTS: During 2007-2011, non-HIV-attributable causes of death with the
      highest rates per 1,000 person-years were heart disease (2.0), non-AIDS cancers
      other than lung cancer (1.4), and accidents (0.8). During 1990-2011, among
      persons with AIDS, the annual rate of death due to HIV-attributable causes
      decreased by 89% (from 122.0 to 13.2), and the rate due to non-HIV-attributable
      causes decreased by 57% (from 20.0 to 8.6), while the percentage of deaths caused
      by non-HIV-attributable causes increased from 11% to 43%. During 2000-2011, among
      persons with HIV infection, the rate of death due to HIV-attributable causes
      decreased by 69% (from 26.4 to 8.3), and the rate due to non-HIV-attributable
      causes decreased by 28% (from 10.5 to 7.6), while the percentage of deaths caused
      by non-HIV-attributable causes increased from 25% to 48%. CONCLUSION: Among HIV
      infected persons, as rates of death due to HIV-attributable causes decreased,
      rates due to non-HIV-attributable causes also decreased, but the percentages of
      deaths due to non-HIV-attributable causes, such as heart disease and non-AIDS
      cancers increased.

PMID- 27708747
TI  - Influence of the First Consultation on Adherence to Antiretroviral Therapy for
      HIV-infected Patients.
AB  - BACKGROUND: Physician attitude influences the way patients cope with diagnosis
      and therapy in chronic severe diseases such as cancer. Previous studies showed
      that such an effect exists in HIV care; it is likely that it begins with the
      first contact with a physician. OBJECTIVE: We aimed to explore in HIV-infected
      persons their perception of the first consultation they had with an HIV
      specialist (PFC-H), and whether this perception correlates with adherence to
      antiretroviral therapy. METHOD: The study was conducted in Grenoble University
      Hospital, France, a tertiary care center. Every antiretroviral-experienced
      patient was asked to freely complete a self-reported, anonymous questionnaire
      concerning retrospective PFC-H, present adherence (Morisky scale), and present
      perceptions and beliefs about medicine (BMQ scale). RESULTS: One hundred and
      fifty-one questionnaires were available for evaluation. PFC-H score and adherence
      were correlated, independently from age, gender, and numbers of pill(s) and of
      pill intake(s) per day. BMQ score also correlated with adherence; structural
      equation analysis suggested that the effect of PFC-H on adherence is mediated by
      positive beliefs. CONCLUSION: These results suggest that for HIV-infected
      persons, the perceptions remaining from the first consultation with an HIV
      specialist physician influence important issues such as adherence and perception
      about medicine. Physicians must be aware of this potentially long-lasting effect.

PMID- 27708748
TI  - Prevalence of the CHEK2 R95* germline mutation.
AB  - BACKGROUND: While germline CHEK2 mutations have been linked to a moderately
      elevated cancer risk, to date, a limited number of such mutations have been
      identified. Recently, we reported a germline nonsense mutation (C283T; R95*),
      introducing an early stop-codon, in two Norwegian patients diagnosed with locally
      advanced breast cancer. Both patients were resistant to anthracycline therapy,
      resembling what has been observed for TP53 mutations. METHODS: In the present
      study, we screened a large population based sample, including 3748 non-cancer
      individuals and 7081 incident cancer cases (breast cancer, n = 1717; prostate
      cancer n = 2501, lung cancer n = 1331 and colorectal cancer n = 1532), for the
      distribution of CHEK2 R95*. RESULTS: We found that 12 individuals (0.11 %)
      carried the R95* variant: 4 non-cancer individuals (0.11 %), 4 breast cancer
      cases (0.23 %), and 4 prostate cancer cases (0.16 %). Although the low number of
      observations precluded formal statistical assessment, our data may indicate an
      elevated risk for breast (OR: 2.19, 95 % CI: 0.55-8.75) and prostate cancer (OR:
      1.5, 95 % CI: 0.36-6.00) associated with CHEK2 R95*. By mining international
      databanks, we found no individuals carrying the R95* mutation, indicating it to
      be restricted to the Norwegian population. CONCLUSION: We provide proof-of
      concept that previously unknown CHEK2 germline mutations may be present in
      certain populations. Notably, germline mutations in tumours are in general missed
      by contemporary massive parallel sequencing strategies, since tumour mutations
      are usually filtered against the germline. The fact that the CHEK2 R95* mutation
      may be associated with resistance to anthracyclines in cancer patients emphasizes
      its possible clinical importance.

PMID- 27708749
TI  - Permanent draft genome of Thermithiobaclillus tepidarius DSM 3134T, a moderately
      thermophilic, obligately chemolithoautotrophic member of the Acidithiobacillia.
AB  - Thermithiobacillus tepidarius DSM 3134T was originally isolated (1983) from the
      waters of a sulfidic spring entering the Roman Baths (Temple of Sulis-Minerva) at
      Bath, United Kingdom and is an obligate chemolithoautotroph growing at the
      expense of reduced sulfur species. This strain has a genome size of 2,958,498 bp.
      Here we report the genome sequence, annotation and characteristics. The genome
      comprises 2,902 protein coding and 66 RNA coding genes. Genes responsible for the
      transaldolase variant of the Calvin-Benson-Bassham cycle were identified along
      with a biosynthetic horseshoe in lieu of Krebs' cycle sensu stricto. Terminal
      oxidases were identified, viz. cytochrome c oxidase (cbb3, EC 1.9.3.1) and
      ubiquinol oxidase (bd, EC 1.10.3.10). Metalloresistance genes involved in
      pathways of arsenic and cadmium resistance were found. Evidence of horizontal
      gene transfer accounting for 5.9 % of the protein-coding genes was found,
      including transfer from Thiobacillus spp. and Methylococcus capsulatus Bath,
      isolated from the same spring. A sox gene cluster was found, similar in structure
      to those from other Acidithiobacillia - by comparison with Thiobacillus thioparus
      and Paracoccus denitrificans, an additional gene between soxA and soxB was found,
      annotated as a DUF302-family protein of unknown function. As the Kelly-Friedrich
      pathway of thiosulfate oxidation (encoded by sox) is not used in
      Thermithiobacillus spp., the role of the operon (if any) in this species remains
      unknown. We speculate that DUF302 and sox genes may have a role in periplasmic
      trithionate oxidation.

PMID- 27708750
TI  - Classification and substrate head-group specificity of membrane fatty acid
      desaturases.
AB  - Membrane fatty acid desaturases are a diverse superfamily of enzymes that
      catalyze the introduction of double bonds into fatty acids. They are essential in
      a range of metabolic processes, such as the production of omega-3 fatty acids.
      However, our structure-function understanding of this superfamily is still
      developing and their range of activities and substrate specificities are broad,
      and often overlapping, which has made their systematic characterization
      challenging. A central issue with characterizing these proteins has been the lack
      of a structural model, which has been overcome with the recent publication of the
      crystal structures of two mammalian fatty acid desaturases. In this work, we have
      used sequence similarity networks to investigate the similarity among over 5000
      related membrane fatty acid desaturase sequences, leading to a detailed
      classification of the superfamily, families and subfamilies with regard to their
      function and substrate head-group specificity. This work will facilitate rapid
      prediction of the function and specificity of new and existing sequences, as well
      as forming a basis for future efforts to manipulate the substrate specificity of
      these proteins for biotechnology applications.

PMID- 27708751
TI  - Dual mode of cell death upon the photo-irradiation of a RuII polypyridyl complex
      in interphase or mitosis.
AB  - Photodynamic therapy (PDT) is an attractive, complementary medical technique to
      chemotherapy. Among the different photosensitizers (PSs) employed, Ru(ii)
      polypyridyl complexes were found to be valid substitutes to porphyrin-based or
      phthalocyanine-based PSs. Here, we confirm that one such complex, namely
      [Ru(bipy)2-dppz-7-methoxy][PF6]2 (Ru65), which localizes in the nucleus of
      various cancer and normal cells, displays cytotoxicity only upon UV-A
      irradiation. Importantly, we disclose the molecular mechanism of the UV-A
      mediated cytotoxic action of Ru65. We demonstrate that Ru65 intercalates in DNA
      and, upon light irradiation, promotes guanine oxidation, resulting in nicks in
      the double helix. We confirm this mechanism of action in living cells, showing
      that the UV-A irradiation of cells loaded with Ru65 results in a transient DNA
      damage response and cell death. Strikingly, the photo-irradiation of Ru65
      triggered distinct mechanisms of cell death in interphase or mitotic cells. The
      former underwent cell cycle arrest at the G2/M phase and massive cytoplasmic
      vacuolation, which was paralleled by an unfolded-protein stress response,
      resulting in a reduction of viability and cell death through a paraptosis-like
      mechanism. On the other hand, the UV-A irradiation of Ru65 in cells synchronized
      by G2/M block-release with a selective CDK1 inhibitor led to blocking mitotic
      entry and rapid cell death through classic apoptotic pathways. Importantly,
      targeting mitotic cells with Ru65 allowed increasing its photo-toxicity by a
      factor of 3.6. Overall, our findings show that the use of a combination of a cell
      cycle inhibitor and a PS targeting the nucleus could open up new avenues in PDT.

PMID- 27708752
TI  - Using Single Colors and Color Pairs to Communicate Basic Tastes II: Foreground
      Background Color Combinations.
AB  - People associate basic tastes (e.g., sweet, sour, bitter, and salty) with
      specific colors (e.g., pink or red, green or yellow, black or purple, and white
      or blue). In the present study, we investigated whether a color bordered by
      another color (either the same or different) would give rise to stronger taste
      associations relative to a single patch of color. We replicate previous findings,
      highlighting the existence of a robust crossmodal correspondence between
      individual colors and basic tastes. On occasion, color pairs were found to
      communicate taste expectations more consistently than were single color patches.
      Furthermore, and in contrast to a recent study in which the color pairs were
      shown side-by-side, participants took no longer to match the color pairs with
      tastes than the single colors (they had taken twice as long to respond to the
      color pairs in the previous study). Possible reasons for these results are
      discussed, and potential applications for the results, and for the testing
      methodology developed, are outlined.

PMID- 27708753
TI  - How Heavy Is an Illusory Length?
AB  - The perception of object properties, such as size and weight, can be subject to
      illusions. Could a visual size illusion influence perceived weight? Here, we
      tested whether the size-weight illusion occurs when lifting two physically
      identical but perceptually different objects, by using an illusion of size.
      Participants judged the weight and length of 11 to 17 cm brass bars with equal
      density to which cardboard arrowheads were attached to create a Muller-Lyer
      illusion. We found that these stimuli induced an illusion in which the bar that
      was visually perceived as being shorter was also perceived as feeling heavier. In
      fact, a 5-mm increase in illusory length corresponded to a decrease in illusory
      weight of 15 g.

PMID- 27708754
TI  - Apparent Biological Motion in First and Third Person Perspective.
AB  - Apparent biological motion is the perception of plausible movements when two
      alternating images depicting the initial and final phase of an action are
      presented at specific stimulus onset asynchronies. Here, we show lower subjective
      apparent biological motion perception when actions are observed from a first
      relative to a third visual perspective. These findings are discussed within the
      context of sensorimotor contributions to body ownership.

PMID- 27708755
TI  - The Anne Boleyn Illusion is a Six-Fingered Salute to Sensory Remapping.
AB  - The Anne Boleyn Illusion exploits the somatotopic representation of touch to
      create the illusion of an extra digit and demonstrates the instantaneous
      remapping of relative touch location into body-based coordinates through visuo
      tactile integration. Performed successfully on thousands, it is also a simple
      demonstration of the flexibility of body representations for use at public
      events, in schools or in the home and can be implemented anywhere by anyone with
      a mirror and some degree of bimanual coordination.

PMID- 27708756
TI  - Plasticity and regeneration of gonads in the annelid Pristina leidyi.
AB  - BACKGROUND: Gonads are specialized gamete-producing structures that, despite
      their functional importance, are generated by diverse mechanisms across groups of
      animals and can be among the most plastic organs of the body. Annelids, the
      segmented worms, are a group in which gonads have been documented to be plastic
      and to be able to regenerate, but little is known about what factors influence
      gonad development or how these structures regenerate. In this study, we aimed to
      identify factors that influence the presence and size of gonads and to
      investigate gonad regeneration in the small asexually reproducing annelid,
      Pristina leidyi. RESULTS: We found that gonad presence and size in asexual adult
      P. leidyi are highly variable across individuals and identified several factors
      that influence these structures. An extrinsic factor, food availability, and two
      intrinsic factors, individual age and parental age, strongly influence the
      presence and size of gonads in P. leidyi. We also found that following head
      amputation in this species, gonads can develop by morphallactic regeneration in
      previously non-gonadal segments. We also identified a sexually mature individual
      from our laboratory culture that demonstrates that, although our laboratory
      strain reproduces only asexually, it retains the potential to become fully
      sexual. CONCLUSIONS: Our findings demonstrate that gonads in P. leidyi display
      high phenotypic plasticity and flexibility with respect to their presence, their
      size, and the segments in which they can form. Considering our findings along
      with relevant data from other species, we find that, as a group, clitellate
      annelids can form gonads in at least four different contexts: post-starvation
      refeeding, fission, morphallactic regeneration, and epimorphic regeneration. This
      group is thus particularly useful for investigating the mechanisms involved in
      gonad formation and the evolution of post-embryonic phenotypic plasticity.

PMID- 27708758
TI  - Quantifying cellular and subcellular stretches in embryonic lung epithelia under
      peristalsis: where to look for mechanosensing.
AB  - Peristalsis begins in the lung as soon as the smooth muscle (SM) forms, and
      persists until birth. As the prenatal lung is filled with liquid, SM action can,
      through lumen pressure, deform tissues far from the immediately adjacent tissues.
      Stretching of embryonic tissues has been shown to have potent morphogenetic
      effects. We hypothesize that these effects are at work in lung morphogenesis. In
      order to refine that broad hypothesis in a quantitative framework, we
      geometrically analyse cell shapes in an epithelial tissue, and individual cell
      deformations resulting from peristaltic waves that completely occlude the airway.
      Typical distortions can be very large, with opposite orientations in the stalk
      and tip regions. Apical distortions are always greater than basal distortions. We
      give a quantitative estimate of the relationship between length of occluded
      airway and the resulting tissue stretch in the distal tip. We refine our analysis
      of cell stresses and strains from peristalsis with a simple mechanical model of
      deformation of cells within an epithelium, which accounts for basic subcellular
      geometry and material properties. The model identifies likely stress
      concentrations near the nucleus and at the apical cell-cell junction. The
      surprisingly large strains of airway peristalsis may serve to rearrange cells and
      stimulate other mechanosensitive processes by repeatedly aligning cytoskeletal
      components and/or breaking and reforming lateral cell-cell adhesions. Stress
      concentrations between nuclei of adjacent cells may serve as a mechanical control
      mechanism guiding the alignment of nuclei as an epithelium matures.

PMID- 27708757
TI  - Measuring cellular traction forces on non-planar substrates.
AB  - Animal cells use traction forces to sense the mechanics and geometry of their
      environment. Measuring these traction forces requires a workflow combining cell
      experiments, image processing and force reconstruction based on elasticity
      theory. Such procedures have already been established mainly for planar
      substrates, in which case one can use the Green's function formalism. Here we
      introduce a workflow to measure traction forces of cardiac myofibroblasts on non
      planar elastic substrates. Soft elastic substrates with a wave-like topology were
      micromoulded from polydimethylsiloxane and fluorescent marker beads were
      distributed homogeneously in the substrate. Using feature vector-based tracking
      of these marker beads, we first constructed a hexahedral mesh for the substrate.
      We then solved the direct elastic boundary volume problem on this mesh using the
      finite-element method. Using data simulations, we show that the traction forces
      can be reconstructed from the substrate deformations by solving the corresponding
      inverse problem with an L1-norm for the residue and an L2-norm for a zeroth-order
      Tikhonov regularization. Applying this procedure to the experimental data, we
      find that cardiac myofibroblast cells tend to align both their shapes and their
      forces with the long axis of the deformable wavy substrate.

PMID- 27708760
TI  - Local modulation of chemoattractant concentrations by single cells: dissection
      using a bulk-surface computational model.
AB  - Chemoattractant gradients are usually considered in terms of sources and sinks
      that are independent of the chemotactic cell. However, recent interest has
      focused on 'self-generated' gradients, in which cell populations create their own
      local gradients as they move. Here, we consider the interplay between
      chemoattractants and single cells. To achieve this, we extend a recently
      developed computational model to incorporate breakdown of extracellular
      attractants by membrane-bound enzymes. Model equations are parametrized, using
      the published estimates from Dictyostelium cells chemotaxing towards cyclic AMP.
      We find that individual cells can substantially modulate their local attractant
      field under physiologically appropriate conditions of attractant and enzymes.
      This means the attractant concentration perceived by receptors can be a small
      fraction of the ambient concentration. This allows efficient chemotaxis in
      chemoattractant concentrations that would be saturating without local breakdown.
      Similar interactions in which cells locally mould a stimulus could function in
      many types of directed cell motility, including haptotaxis, durotaxis and even
      electrotaxis.

PMID- 27708759
TI  - A mathematical model of GTPase pattern formation during single-cell wound repair.
AB  - Rho GTPases are regulatory proteins whose patterns on the surface of a cell
      affect cell polarization, cell motility and repair of single-cell wounds. The
      stereotypical patterns formed by two such proteins, Rho and Cdc42, around laser
      injured frog oocytes permit experimental analysis of GTPase activation,
      inactivation, segregation and crosstalk. Here, we review the development and
      analysis of a spatial model of GTPase dynamics that describe the formation of
      concentric zones of Rho and Cdc42 activity around wounds, and describe how this
      model has provided insights into the roles of the GTPase effector molecules
      protein kinase C (PKCbeta and PKCeta) and guanosine nucleotide dissociation
      inhibitor (GDI) in the wound response. We further demonstrate how the use of a
      'sharp switch' model approximation in combination with bifurcation analysis can
      aid mapping the model behaviour in parameter space (approximate results confirmed
      with numerical simulation methods). Using these methods in combination with
      experimental manipulation of PKC activity (PKC overexpression (OE) and dominant
      negative conditions), we have shown that: (i) PKCbeta most probably acts by
      enhancing existing positive feedbacks (from Rho to itself via the guanosine
      nucleotide exchange factor domain of Abr, and from Cdc42 to itself), (ii) PKCeta
      most probably increases basal rates of inactivation (or possibly decreases basal
      rates of activation) of Rho and Cdc42, and (iii) the graded distribution of
      PKCeta and its effect on initial Rho activity accounts for inversion of zones in
      a fraction (20%) of PKCeta OE cells. Finally, we speculate that GDIs (which
      sequester GTPases) may have a critical role in defining the spatial domain, where
      the wound response may occur. This paper provides a more thorough exposition of
      the methods of analysis used in the investigation, whereas previous work on this
      topic was addressed to biologists and abbreviated such discussion.

PMID- 27708761
TI  - Collective migration under hydrodynamic interactions: a computational approach.
AB  - We consider a generic model for cell motility. Even if a comprehensive
      understanding of cell motility remains elusive, progress has been achieved in its
      modelling using a whole-cell physical model. The model takes into account the
      main mechanisms of cell motility, actin polymerization, actin-myosin dynamics and
      substrate mediated adhesion (if applicable), and combines them with steric cell
      cell and hydrodynamic interactions. The model predicts the onset of collective
      cell migration, which emerges spontaneously as a result of inelastic collisions
      of neighbouring cells. Each cell here modelled as an active polar gel is
      accomplished with two vortices if it moves. Upon collision of two cells, the two
      vortices which come close to each other annihilate. This leads to a rotation of
      the cells and together with the deformation and the reorientation of the actin
      filaments in each cell induces alignment of these cells and leads to persistent
      translational collective migration. The effect for low Reynolds numbers is as
      strong as in the non-hydrodynamic model, but it decreases with increasing
      Reynolds number.

PMID- 27708762
TI  - Review on experiment-based two- and three-dimensional models for wound healing.
AB  - Traumatic and chronic wounds are a considerable medical challenge that affects
      many populations and their treatment is a monetary and time-consuming burden in
      an ageing society to the medical systems. Because wounds are very common and
      their treatment is so costly, approaches to reveal the responses of a specific
      wound type to different medical procedures and treatments could accelerate
      healing and reduce patient suffering. The effects of treatments can be forecast
      using mathematical modelling that has the predictive power to quantify the
      effects of induced changes to the wound-healing process. Wound healing involves a
      diverse and complex combination of biophysical and biomechanical processes. We
      review a wide variety of contemporary approaches of mathematical modelling of gap
      closure and wound-healing-related processes, such as angiogenesis. We provide
      examples of the understanding and insights that may be garnered using those
      models, and how those relate to experimental evidence. Mathematical modelling
      based simulations can provide an important visualization tool that can be used
      for illustrational purposes for physicians, patients and researchers.

PMID- 27708763
TI  - Multimodality imaging and mathematical modelling of drug delivery to
      glioblastomas.
AB  - Patients diagnosed with glioblastoma, an aggressive brain tumour, have a poor
      prognosis, with a median overall survival of less than 15 months. Vasculature
      within these tumours is typically abnormal, with increased tortuosity, dilation
      and disorganization, and they typically exhibit a disrupted blood-brain barrier
      (BBB). Although it has been hypothesized that the 'normalization' of the
      vasculature resulting from anti-angiogenic therapies could improve drug delivery
      through improved blood flow, there is also evidence that suggests that the
      restoration of BBB integrity might limit the delivery of therapeutic agents and
      hence their effectiveness. In this paper, we apply mathematical models of blood
      flow, vascular permeability and diffusion within the tumour microenvironment to
      investigate the effect of these competing factors on drug delivery. Preliminary
      results from the modelling indicate that all three physiological parameters
      investigated-flow rate, vessel permeability and tissue diffusion coefficient
      interact nonlinearly to produce the observed average drug concentration in the
      microenvironment.

PMID- 27708764
TI  - Comparison of cell migration mechanical strategies in three-dimensional matrices:
      a computational study.
AB  - Cell migration on a two-dimensional flat surface has been extensively studied and
      is generally characterized by a front-protrusion-rear-contraction process. In a
      three-dimensional (3D) environment, on the other hand, cells adopt multiple
      migration strategies depending on the cell type and the properties of the
      extracellular matrix (ECM). By using computer simulations, we find that these
      migration strategies can be classified by various spatial-temporal dynamics of
      actin protrusion, actin-myosin contraction and actin-ECM adhesion. We demonstrate
      that if we include or exclude proteolysis of ECM, and vary adhesion dynamics and
      spatial distributions of protrusion, contraction and adhesion, our model can
      reproduce six experimentally observed motility modes: mesenchymal, chimneying,
      amoeboid, blebbing, finger-like protrusion and rear-squeezing cell locomotory
      behaviours. We further find that the mode of the cell motility evolves in
      response to the ECM density and adhesion detachment rate. The model makes non
      trivial predictions about cell speed as a function of the adhesion strength, and
      ECM elasticity and mesh size.

PMID- 27708765
TI  - Prediction of traction forces of motile cells.
AB  - When crawling on a flat substrate, living cells exert forces on it via adhesive
      contacts, enabling them to build up tension within their cytoskeleton and to
      change shape. The measurement of these forces has been made possible by traction
      force microscopy (TFM), a technique which has allowed us to obtain time-resolved
      traction force maps during cell migration. This cell 'footprint' is, however, not
      sufficient to understand the details of the mechanics of migration, that is how
      cytoskeletal elements (respectively, adhesion complexes) are put under tension
      and reinforce or deform (respectively, mature and/or unbind) as a result. In a
      recent paper, we have validated a rheological model of actomyosin linking
      tension, deformation and myosin activity. Here, we complement this model with
      tentative models of the mechanics of adhesion and explore how closely these
      models can predict the traction forces that we recover from experimental
      measurements during cell migration. The resulting mathematical problem is a PDE
      set on the experimentally observed domain, which we solve using a finite-element
      approach. The four parameters of the model can then be adjusted by comparison
      with experimental results on a single frame of an experiment, and then used to
      test the predictive power of the model for following frames and other
      experiments. It is found that the basic pattern of traction forces is robustly
      predicted by the model and fixed parameters as a function of current geometry
      only.

PMID- 27708766
TI  - Hybrid vertex-midline modelling of elongated plant organs.
AB  - We describe a method for the simulation of the growth of elongated plant organs,
      such as seedling roots. By combining a midline representation of the organ on a
      tissue scale and a vertex-based representation on the cell scale, we obtain a
      multiscale method, which is able to both simulate organ growth and incorporate
      cell-scale processes. Equations for the evolution of the midline are obtained,
      which depend on the cell-wall properties of individual cells through appropriate
      averages over the vertex-based representation. The evolution of the organ midline
      is used to deform the cellular-scale representation. This permits the
      investigation of the regulation of organ growth through the cell-scale transport
      of the plant hormone auxin. The utility of this method is demonstrated in
      simulating the early stages of the response of a root to gravity, using a vertex
      based template acquired from confocal imaging. Asymmetries in the concentrations
      of auxin between the upper and lower sides of the root lead to bending of the
      root midline, reflecting a gravitropic response.

PMID- 27708768
TI  - Roxarsone induces angiogenesis via PI3K/Akt signaling.
AB  - BACKGROUND: 3-Nitro-4-hydroxy phenyl arsenic acid, roxarsone, is widely used as
      an organic arsenic feed additive for livestock and poultry, which may increase
      the level of arsenic in the environment and the risk of exposure to arsenic in
      human. Little information is focused on the angiogenesis roxarsone-induced and
      its mechanism at present. This paper aims to study the role of PI3K/Akt signaling
      in roxarsone-induced angiogenesis in rat vascular endothelial cells and a mouse
      B16-F10 melanoma xenograft model. RESULTS: The results showed that treatment with
      0.1-10.0 umol/L roxarsone resulted in an increase in the OD rate in the MTT
      assay, the number of BrdU-positive cells in the proliferation assay, the
      migration distance in the scratch test and the number of meshes in tube formation
      assay. Further, treatment with 1.0 umol/L roxarsone was associated with
      significantly higher phosphorylation of PI3K/Akt and expression of VEGF than the
      control treatment. The PI3K inhibitor was found to significantly combat the
      effects of 1.0 umol/L roxarsone. Furthermore, roxarsone treatment was observed to
      increase the weight and volume of B16-F10 xenografts and VEGF expression and
      PI3K/Akt phosphorylation in a dose-dependent manner, with the 25 mg/kg dose
      having significant effects. CONCLUSIONS: These results demonstrate that roxarsone
      has the ability to promote growth and tube formation in vascular endothelial
      cells and the growth of mouse B16-F10 xenografts. Further, the findings also
      indicate that PI3K/Akt signaling plays a regulatory role in roxarsone-induced
      angiogenesis in vivo and in vitro.

PMID- 27708767
TI  - Progress and perspectives in signal transduction, actin dynamics, and movement at
      the cell and tissue level: lessons from Dictyostelium.
AB  - Movement of cells and tissues is a basic biological process that is used in
      development, wound repair, the immune response to bacterial invasion, tumour
      formation and metastasis, and the search for food and mates. While some cell
      movement is random, directed movement stimulated by extracellular signals is our
      focus here. This involves a sequence of steps in which cells first detect
      extracellular chemical and/or mechanical signals via membrane receptors that
      activate signal transduction cascades and produce intracellular signals. These
      intracellular signals control the motile machinery of the cell and thereby
      determine the spatial localization of the sites of force generation needed to
      produce directed motion. Understanding how force generation within cells and
      mechanical interactions with their surroundings, including other cells, are
      controlled in space and time to produce cell-level movement is a major challenge,
      and involves many issues that are amenable to mathematical modelling.

PMID- 27708769
TI  - Does dental health of 6-year-olds reflect the reform of the Israeli dental care
      system?
AB  - BACKGROUND: The National health insurance law enacted in 1995 did not include
      dental care in its basket of services. Dental care for children was first
      included in 2010, initially up till 8 years of age. The eligibility age rose to
      12 years in 2013. The dental survey of 6 year-olds in 2007 found that the average
      of decayed, missing and filled teeth index (dmft) was 3.31 and 35 % of children
      were caries free. The current cross sectional survey of dental health for 6 year
      olds was conducted as a comparison to the pre-reform status. METHODS: Twenty
      three local authorities were randomly selected nationwide. Two Grade 1 classes
      were randomly chosen in each. The city of Jerusalem was also included in the
      survey because of its size. The children were examined according to the WHO Oral
      Health Survey Methods 4th ed protocol. The dental caries index for deciduous
      teeth (dmft: decayed, missing, filled teeth) was calculated. RESULTS: One
      thousand two hundred ten children were examined. 61.7 % of the children suffered
      from dental decay and only 38.3 % were caries free. The mean dmft was 2.56; d =
      1.41 (teeth with untreated caries), f = 1.15 (teeth damaged by decay and
      restored), virtually none were missing due to caries. Dental caries prevalence
      was rather consistent, an average of over 2 teeth affected per child. Although
      there is no major change in comparison to former surveys, there is more treated
      than untreated disease. In the present survey the f component is higher than in
      the past, especially in the Jewish sector where it is the main component. It is
      still lower in the Arab sector. CONCLUSIONS: Although the level of dental disease
      remained rather constant, an increase in the treatment component was observed. In
      order to reduce caries prevalence, preventive measures such as school dental
      services and drinking water fluoridation should be extended and continued.
      Primary preventive dental services should be established for children from birth,
      with an emphasis on primary health care and educational settings, such as family
      health centers and kindergartens.

PMID- 27708770
TI  - The cytotoxic mechanisms of disulfiram and copper(ii) in cancer cells.
AB  - The anticancer activity of disulfiram (DS) is copper(ii) (Cu)-dependent. This
      study investigated the anticancer mechanisms of DS/Cu using in vitro cytotoxicity
      and metabolic kinetic analysis. Our study indicates that DS/Cu targets cancer
      cells by the combination of two types of actions: (1) instant killing executed by
      DS/Cu reaction generated reactive oxygen species; (2) delayed cytotoxicity
      introduced by the end product, DDC-Cu. Nanoencapsulation of DS might shed light
      on repositioning of DS into cancer treatment.

PMID- 27708771
TI  - Decision making on helminths in cattle: diagnostics, economics and human
      behaviour.
AB  - Helminth infections of cattle affect productivity in all classes of stock, and
      are amongst the most important production-limiting diseases of grazing ruminants.
      Over the last decade, there has been a shift in focus in the diagnosis of these
      infections from merely detecting presence/absence of infection towards detecting
      its impact on production. This has been facilitated by studies observing
      consistent negative correlations between helminth diagnostic test results and
      measures of productivity. Veterinarians are increasingly challenged to consider
      the economic aspects of their work, and the use of these tests should now be
      integrated in economic evaluation frameworks for improved decision making. In
      this paper, we review recent insights in the farm-specific economic impact of
      helminth infections on dairy cattle farms as well as in farmer attitudes and
      behaviour regarding helminth control. Combining better economic impact
      assessments of helminth infections together with a deeper understanding of the
      non-economic factors that drive a farmer's animal health decisions should result
      in more effective control strategies and increased farmer satisfaction.

PMID- 27708773
TI  - Determination of basal ileal endogenous losses and standardized ileal
      digestibility of amino acids in barley fed to growing pigs.
AB  - BACKGROUND: Basal ileal endogenous amino acid (AA) losses (IAAend) and
      standardized ileal digestibility (SID) values of cereal grains, such as barley,
      are apparently underestimated when determined according to the nitrogen (N)-free
      method. Regression analysis between the dietary apparent ileal digestible content
      (cAID) and total crude protein (CP) and AA can be considered as alternative
      approach to obtain more accurate values for IAAend and SID of AA in cereal
      grains. METHODS: Eight hulled barley genotypes were used, with barley being the
      only source of CP and AA in the assay diets. The diets contained 95 % as-fed of
      these eight barley genotypes each, ranging in CP content between 109.1 and 123.8
      g/kg dry matter (DM). Nine ileally T-cannulated barrows, average body weight (BW)
      30 +/- 2 kg, were allotted to a row-column design comprising eight periods with 6
      d each and nine pigs. On d 5 and the night of d 6 of every period, ileal digesta
      were collected for a total of 12 h. The IAAend and the SID were determined by
      linear regression analysis between cAID and total dietary CP and AA. RESULTS:
      There exist linear relationships between cAID and total CP and AA (P < 0.001).
      The IAAend of CP, Lys, Met, Thr and Trp amounted to 35.34, 1.08, 0.25, 1.02 and
      0.38 g/kg DM intake (DMI), respectively, which are greater compared to average
      IAAend determined previously under N-free feeding conditions. The SID of CP, Lys,
      Met, Thr and Trp was 90, 79, 85, 79 and 86 %, respectively, and was greater when
      compared to tabulated values. Moreover, these SID values were greater than those
      reported in literature, based on correction of apparent ileal digestibility (AID)
      of CP and AA for their IAAend values. Summarized, the results of the present
      regression analysis indicate greater IAAend in barley-based diets compared to
      those obtained by N-free feeding. CONCLUSIONS: For low-protein feed ingredients
      like barley the regression method may be preferred over correction of AID values
      for their IAAend determined under N-free feeding conditions, as intercepts and
      slopes of the linear regression equations between cAID and total dietary CP and
      AA provide direct estimates of IAAend and SID of CP and AA in the presence of the
      assay feed ingredient.

PMID- 27708772
TI  - Single-cell intracellular nano-pH probes.
AB  - Within a large clonal population, such as cancerous tumor entities, cells are not
      identical, and the differences between intracellular pH levels of individual
      cells may be important indicators of heterogeneity that could be relevant in
      clinical practice, especially in personalized medicine. Therefore, the detection
      of the intracellular pH at the single-cell level is of great importance to
      identify and study outlier cells. However, quantitative and real-time
      measurements of the intracellular pH of individual cells within a cell population
      is challenging with existing technologies, and there is a need to engineer new
      methodologies. In this paper, we discuss the use of nanopipette technology to
      overcome the limitations of intracellular pH measurements at the single-cell
      level. We have developed a nano-pH probe through physisorption of chitosan onto
      hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The
      dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of
      0.09 units. We have performed single-cell intracellular pH measurements using non
      cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231
      and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time
      continuous single-cell pH measurement capability of the sensor, showing the
      cellular pH response to pharmaceutical manipulations. These findings suggest that
      the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at
      the single-cell level with high temporal and spatial resolution.

PMID- 27708775
TI  - Incidence of sickness absence by type of employment contract: one year follow-up
      study in Spanish salaried workers.
AB  - BACKGROUND: To examine the differences in the incidence of registered sickness
      absence by type of employment contract in a large representative sample of
      salaried workers in Spain in 2009. METHOD: A study of 653,264 salaried workers
      covered by the Social Security system who had 133,724 sickness absence episodes
      in 2009. Crude and adjusted rate ratios and their corresponding 95 % confidence
      intervals (CIs) were calculated with Poisson regression models. RESULTS: The
      incidence rate per 100 workers-year of sickness absence for temporary workers (IR
      = 32.2) was slightly higher than that of permanent workers (IR = 28.9). This
      pattern was observed in both men (RR = 1.12; 95 % CI 1.10-1.14) and women (RR
      1.11; 95 % CI 1.09-1.12). However, after adjusting for age, company size, and
      occupational category, the differences disappeared in men (aRR = 1.01; 95 % CI
      0.99-1.02) and decreased in women (aRR = 1.06; 95 % CI 1.04-1.07). CONCLUSION:
      Our findings provide evidence on the independence of sickness absence benefits
      from the type of employment contract as well as on the nonexistence of incentives
      for taking sickness absence in workers with a permanent employment contract. In
      the context of increasing market flexibility, these results show a positive
      functioning of the Social Security system.

PMID- 27708774
TI  - Effects of chronic heat stress on granulosa cell apoptosis and follicular atresia
      in mouse ovary.
AB  - BACKGROUND: Heat stress is known to alter follicular dynamics and granulosa cell
      function and may contribute to the diminished reproductive efficiency commonly
      observed in mammals during the summer. Although several investigators have
      studied heat-induced ovarian injury, few reports have focused on the effects of
      chronic heat stress on ovarian function and the molecular mechanisms through
      which it induces ovarian injury. METHODS: In Exp. 1, 48 female mice were assigned
      to a control or heat-stressed treatment. After exposure to a constant temperature
      of 25  degrees C for 7, 14, 21 or 28 d (n = 6) or to 42  degrees C for 3 h per d
      for 7, 14, 21 or 28 d (n = 6), the mice were euthanized and their ovaries were
      analyzed for follicular atresia, granulosa cell apoptosis, changes in the
      abundance of HSP70 protein and serum concentrations of estradiol. In Exp. 2, the
      expression of HSP70 and aromatase was quantified in antral follicles cultured in
      vitro at 37 or 42  degrees C for 24 h. In Exp. 3, granulosa cells from ovaries
      maintained at 37 or 41  degrees C for 2 h were analyzed for their expression of
      HSP70, Bim, caspase-3 and cleaved caspase-3. RESULTS: In Exp. 1, body weight and
      food intake of heat-stressed mice decreased (P < 0.05) compared with control mice
      while the concentration of estradiol in serum was lower (P < 0.05) in heat
      stressed mice than in control mice. Compared with control mice, the percentage of
      atretic follicles and the number of antral follicles with severe apoptotic
      signals were increased (P < 0.05) after 21 d of heat-stressed treatment. HSP70
      protein was more abundant (P < 0.05) in heat-stressed mice than control mice. In
      Exp. 2, heat stress increased HSP70 and decreased aromatase proteins (P < 0.05)
      in antral follicles. In Exp. 3, TUNEL-positive granulosa cells from heat-stressed
      ovaries were observed concomitant with a significant increase in HSP70, Bim and
      cleaved caspase-3 protein. CONCLUSION: Heat-stress in mice decrease estradiol in
      serum and aromatase in antral follicles but increased number of atretic follicles
      and granulosa cell undergoing apoptosis which may explain the decreased fertility
      commonly observed in heat-stressed animals.

PMID- 27708776
TI  - Implementing Smarter Lunchrooms Makeovers in New York state middle schools: an
      initial process evaluation.
AB  - BACKGROUND: This paper presents design and findings from the process evaluation
      of a randomized controlled trial (RCT) testing the effectiveness of Smarter
      Lunchrooms Movement (SLM) interventions to encourage consumption of either fruit,
      vegetables, or unflavored milk in middle school cafeterias (grades 6-8, typically
      children ages 10-14 years). Using the RE-AIM (Reach, Effectiveness, Adoption,
      Implementation, and Maintenance) framework adapted for environmental
      interventions, the process evaluation monitored fidelity to SLM protocol,
      determined barriers and facilitators influencing fidelity, and identified the
      training and support needs of implementers. METHODS: Under research team
      guidance, community partners (interventionists) assisted school food service
      staff (providers) with a six week implementation of protocol items in 13 public
      middle school cafeterias (two milk treatment, three vegetable treatment, four
      fruit treatment, and four control) in New York State during the 2013-2014
      academic year. Process evaluation measures included semi-quantitative measures of
      implementation and maintenance (lunchroom audits) and qualitative data
      (environmental assessments and semi-structured interviews with school food
      service staff). Analyses identified challenges and opportunities for improving
      intervention delivery. RESULTS: Approximately 75 % of enrolled students
      participated in school lunch programs and thus were exposed to the SLM
      intervention. Findings indicated potential contamination by other nutrition
      related activities in the lunchroom and larger school environment may have
      affected the intervention impact. Modest implementation fidelity scores were
      observed for intervention treatments. Providers reported treatments were
      acceptable and feasible, however interventionists confirmed motivation and
      perceived effectiveness varied among schools. Post-intervention audits revealed
      limited maintenance of intervention protocols. Strategies to enhance buy-in and
      communication among providers and increased interventionist support are
      recommended. CONCLUSIONS: RE-AIM was a valuable framework for this process
      evaluation. Results highlighted implementation barriers and facilitators, and
      findings will enhance interpretation of forthcoming outcome data. Results will
      inform future iterations of the SLM RCT and provide valuable insights for those
      designing environmental interventions in school cafeterias.

PMID- 27708778
TI  - Getting to grips with the obesity epidemic in Europe.
AB  - Obesity is a global epidemic. It is responsible for increased patient morbidity
      and mortality. Significant related pathologies including diabetes mellitus
      compound the overall risks. Obesity is a significant financial burden. This
      includes direct and indirect medical costs, amounting to millions of euros each
      year. Multiple European studies have outlined a steady incline in obesity
      prevalence rates. Tackling obesity is no easy task. Policy makers aiming to
      reduce obesity rates should adopt an evidence-based approach. This entails
      adopting both micro- and macro-interventions tweaked to each country's individual
      requirements. The ideal way forward would be to tackle obesity from the
      individual, population-wide and food industry angles. The key towards a
      successful intervention is for each country to carry out well-planned health
      examination studies, in an attempt to pin point local risk factors. Having a
      correct individualized picture, each country can move forward and draw policies
      and interventional procedures. The aim should be to primarily improve the quality
      of life. Second, the country's capital expenditure is also reduced.

PMID- 27708777
TI  - Cough: impact, beliefs, and expectations from a national survey.
AB  - BACKGROUND: Cough is one of the most common discomforts affecting general
      population, which can disrupt subjects' quality of life due to its physical,
      social, and psychological effects. Aim of the study was to investigate the impact
      of cough and related beliefs of general population. METHODS: A cross-sectional
      telephone survey was carried out by means of a specific, validated questionnaire
      on a representative sample of Italian general population. All the interviews were
      carried out according to the Computer Assisted Telephone Interview (CATI)
      methodology by expert, professional interviewers. Distributions of all answers
      were calculated in the overall sample. RESULTS: A total of 1,251 subjects (mean
      age: 49 years; females 44.2 %) completed the interviews. The overall number of
      telephone calls was 5362, and the corresponding redemption rate was 1/4.3 (23.%).
      The sample was representative of national population in terms of geographical
      distribution, age, gender, and smoking habit. The majority of respondents was
      convinced that cough is merely a symptom of several different diseases, but 46.4
      % of respondents affirmed that cough should be regarded as "a disease" per se.
      Only 29.1 % of subjects say that they usually do not complain of any cough over
      the year, while 18.4 % reported >= 3 episodes of cough/year. These episodes have
      a duration ranging 10-30 days in 19.9 % of subjects, and > 30 days in 6.9 % of
      subjects. The majority of respondents is worried about their cough only after 1
      week, but 76.9 % of subjects is much more worried if cough affects a child. After
      a few days of cough, 23.1 % of subjects use domestic remedies; 20.9 % ask their
      pharmacist, and 33.4 % their doctor, being GPs (69.6 %) and lung physicians (16.2
      %) the most asked professionals. The occurrence of bronchitis, pneumonia, upper
      airway infections, and allergic troubles are the most feared events. The majority
      of respondents are convinced that antibiotics and steroids should not be regarded
      as the gold standard for treating persistent cough (61.2 and 58.2 %,
      respectively), while anti-tussive drugs and aerosols in general are regarded as
      the most effective strategies (69.1 and 74.1 %, respectively). Moreover, 33.8 %
      of the sample is in favour of homeopathic drugs, while 23.2 % had already used an
      homeopathic anti-tussive syrup, and 27.6 % of subjects are really interested in
      using the homeopathic approach. The willingness to pay for an effective anti
      tussive remedy was: 46.3 % up to 10 ?; 27.8 % up to 20 ?, and 13.3 % more than 20
      ?. CONCLUSIONS: Cough confirms its high impact in Italy, and a substantial
      proportion of individuals regards cough as "a disease". Only one out of three
      Italians refers to their doctor, but when cough is already persistent. Cough in
      children is much more feared than in adults. The majority of Italians have a
      proper and conservative position versus both antibiotic and the systemic steroid
      uses against cough. The Italian attitude to aerosol therapy confirms very high.
      Differently from the cough guidelines, anti-tussive drugs are highly valued among
      Italian people. The attitude and the interest to homeopathic anti-tussive
      remedies proves high. Finally, the willingness to pay for an effective anti
      tussive remedy is quite high in Italy.

PMID- 27708779
TI  - Prospective study of percutaneous tracheostomy: Role of bronchoscopy and surgical
      technique.
AB  - OBJECTIVE: Percutaneous tracheostomy is a common procedure but varies
      considerably in approach. The aim of our study was to evaluate the need for
      intraoperative bronchoscopy and to compare various surgical techniques. METHODS:
      During 1 year all percutaneous tracheostomies in three intensive care units were
      prospectively documented according to a unified protocol. In one unit,
      bronchoscopy was used routinely and in others only during the study. RESULTS: A
      total of 111 subjects (77 males) with median age 64 (range, 18-86) years and body
      mass index 25.4 (range, 15.9-50.7) were included. In unit A, tracheal wall was
      directly exposed; in unit B, limited dissection to enable tracheal palpation was
      made. In both units, bronchoscopy was used to check the location of an already
      inserted guiding needle; needle position required correction in 8% and 12% of
      cases, respectively. In unit C, in tracheostomies without pretracheal tissue
      dissection, bronchoscopy was used to guide needle insertion; needle position
      required correction in 66% of cases. Median duration of operations performed by
      thoracic surgeons and residents was 10 (range, 3-37) min and by intensive care
      doctors and residents was 16.5 (range, 3-63) min (p < 0.001). Time from the
      beginning of preparations for tracheostomy until the end of the whole procedure
      was median 32 min for bedside tracheostomies and 64 min for operations in the
      operating theatre (p < 0.001). CONCLUSION: Limited pretracheal tissue dissection
      enabled proper guiding needle insertion and bronchoscopy was rarely needed.
      Percutaneous tracheostomies performed by thoracic surgeons took less time, and
      duration of the whole procedure was remarkably shorter when performed at bedside.

PMID- 27708780
TI  - Therapeutic drug monitoring of mexiletine at a large academic medical center.
AB  - INTRODUCTION: The therapeutic trough range for mexiletine (0.8-2 mcg/mL) was
      largely established in the setting of arrhythmia prophylaxis following myocardial
      infarction. OBJECTIVE: Describe the usage patterns of serum mexiletine
      concentrations and the impact of these concentrations on mexiletine dosing in
      modern practice for ventricular arrhythmia treatment. METHODS: A single-center,
      retrospective analysis was conducted using the electronic medical record to
      identify serum mexiletine concentrations drawn between December 2004 and December
      2014. The primary endpoint was the incidence of mexiletine concentrations drawn
      as troughs. Secondary outcomes included the incidence of mexiletine
      concentrations that prompted a dose change, association between adverse events
      and elevated concentrations, and association between baseline characteristics and
      mexiletine concentrations. RESULTS: A total of 237 individual concentrations were
      included for analysis with 109 (46.0%) drawn appropriately as trough
      concentrations. Only 31 (13.1%) of the 237 concentrations drawn prompted a dose
      change. Mexiletine was primarily used for the treatment of ventricular
      arrhythmias (96.2%), and 108 (45.6%) concentrations were drawn in an effort to
      assess efficacy. The median concentration was statistically different between
      patients with and without an adverse event (0.8 vs 0.7 mcg/mL, respectively; p =
      0.017), but may not represent a clinical significance. Patients with hepatic
      dysfunction had higher median concentrations compared to those without hepatic
      dysfunction (1.30 vs 1.07 mcg/mL; p = 0.01). CONCLUSION: Mexiletine
      concentrations are often drawn at inappropriate times and seldom influence a dose
      change. This study suggests that routine monitoring of mexiletine concentrations
      may not be necessary; however, therapeutic drug monitoring may be considered in
      patients with hepatic dysfunction or to confirm mexiletine absorption in patients
      where this represents a concern.

PMID- 27708781
TI  - Psychosis: call a surgeon? A rare etiology of psychosis requiring resection.
AB  - OBJECTIVE: Anti-N-methyl-d-aspartate receptor encephalitis is a rare but emerging
      cause of autoimmune encephalitis. Our objective is to present a case of this rare
      disease while highlighting the importance of an aggressive search for underlying
      malignancy as well as the common mischaracterization of primary psychiatric
      illness that occurs in these patients. METHODS: A young Caucasian female with no
      known psychiatric history presented with acute onset of seizures and psychosis.
      RESULTS: Magnetic resonance imaging abdomen and pelvis showed a 6-mm ovarian
      teratoma which was not visualized on initial computed tomographic scans.
      Pathology was consistent with a mature teratoma. Both serum and cerebrospinal
      fluid N-methyl-d-aspartate receptor antibodies were positive. CONCLUSION: An
      exhaustive search for underlying malignancy and specifically ovarian teratoma in
      young women should be completed in these patients. Diagnosis often is delayed
      given the prominent psychiatric manifestations and providers should be aware and
      strongly consider this in younger women with acute onset of neuropsychiatric
      symptoms.

PMID- 27708782
TI  - Delayed Type IIIb endoleak secondary to graft fabric tear 7 years following
      implantation of a Medtronic Talent endovascular aortic device: A case report and
      review of the literature.
AB  - OBJECTIVES: To report a rare case of delayed Type IIIb endoleak secondary to
      fabric tear following implantation of a Medtronic Talent endovascular device.
      METHODS: A 83-year old gentleman underwent elective endovascular aneurysm repair
      for infrarenal abdominal aortic aneurysm with a Medtronic bifurcated stent graft
      in 2008. RESULTS: Seven years after the initial repair, imaging surveillance
      revealed significant endoleak and brisk aneurysm sac expansion due to Type IIIb
      endoleak secondary to endograft limb fabric tear. CONCLUSIONS: This case
      illustrates the imperative role of imaging surveillance in detection of long-term
      endovascular aneurysm repair complications. Furthermore, we discuss exclusion of
      the graft tear with aortouniiliac stent grafting as the treatment for this
      complication.

PMID- 27708783
TI  - Sperm DNA damage and assisted reproductive technologies: reasons to be cautious!

PMID- 27708785
TI  - Erratum to: The Sports-Related Injuries and Illnesses in Paralympic Sport Study
      (SRIIPSS): a study protocol for a prospective longitudinal study.
AB  - [This corrects the article DOI: 10.1186/s13102-016-0053-x.].

PMID- 27708784
TI  - KIR repertory in patients with hematopoietic diseases and healthy family members.
AB  - BACKGROUND: Since the discovery of specific histocompatibility, literature has
      associated genes involved in the immune response, like the Human Leucocyte
      Antigen (HLA), with a better prognosis in transplantation. However, other non-HLA
      genes may also influence the immune process, such as the genes encoding the
      immunoglobulin-like receptors of natural killer cells (KIRs). The discovery that
      NK cell KIR receptors interact with conservative epitopes (C1, C2, Bw4) presented
      in HLA class I molecules that are genetically polymorphic, also observed in KIR
      genes, led to the investigation of the relevance of the KIR system to
      hematopoietic stem cell transplant. The cure of patients with leukemias and other
      hematological malignancies after bone marrow transplantation (BMT) has been
      attributed in part to the ability of the donor immune cells, present in the
      graft, to recognize and eliminate neoplastic cells of the patient. The cytotoxic
      activity of NK cells is mediated by the absence of HLA class I-specific ligands
      on the target cell surface to inhibitory KIR receptors (hypothesis of "missing
      self"). METHODS: We analyzed, by PCR typing-SSOP technique, the presence or
      absence of 16 KIR genes and haplotypes of 39 patients with hematopoietic
      disorders and 136 healthy individuals from Parana State. The comparisons made
      between the patient and control group were performed using chi2 test or Fisher
      exact test (bilateral p-value), as appropriated. Significance level was
      considered when p-value <= 0.05. RESULTS: Framework genes KIR3DL3, KIR3DP1,
      KIR2DL4 and KIR3DL2 were positive in all samples. The comparison between KIR
      repertoire of patients and healthy individuals revealed significant differences
      (p < 0.05) in inhibitors genes KIR2DL2 (p = 0.0005) and KIR2DL5 (p = 0.0067) and
      activating genes KIR2DS1 (p = 0.0013), KIR2DS2 (p = 0.0038), KIR2DS3 (p = 0.0153)
      that are more frequent in controls than in patients. The KIR2DS3 was
      significantly more frequent (p = 0.0031) in patients with acute myeloid leukemia
      (AML) when compared to patients with acute lymphoblastic leukemia (ALL). We
      observed a higher frequency of haplotype A (59 %) in the patients. CONCLUSION:
      Our data suggests that susceptibility to leukemia can be influenced, at least,
      partly byKIR receptors.

PMID- 27708787
TI  - Air pollution and urinary n-acetyl-B-glucosaminidase levels in residents living
      near a cement plant.
AB  - BACKGROUND: To identify adverse renal effects due to air pollution derived from a
      cement plant in Korea. Urinary n-acetyl-B-glucosaminidase (U-NAG) levels in
      residents living near a cement plant were compared to those in a group who lived
      farther away from the plant. METHODS: From June to August 2013 and from August to
      November 2014, laboratory tests for U-NAG and heavy metal were conducted on 547
      study participants. Based on the level of air pollution exposure, subjects were
      divided into the "less exposed group," (LEG) which consisted of 66 persons who
      lived more than 5 km away from the cement plant, the "more exposed group from the
      rural area" (MEG-R), which consisted of 272 persons, and the "more exposed group
      from downtown area" (MEG-D), which consisted of 209 persons who lived within a 1
      km radius of the cement plant. U-NAG levels >5.67 U/L were defined as "higher U
      NAG" levels. We compared the prevalence of higher U-NAG levels and estimated the
      adjusted odds ratio (OR) by air pollution exposure using a chi-square test and
      multiple logistic regression analysis. Further, we estimated the interaction
      between air pollution exposure and heavy metal exposure in renal toxicity.
      RESULTS: The OR of higher U-NAG levels by MEG-D and MEG-R compared to LEG was
      2.13 (95 % CI 0.86-4.96) and 4.79 (95 CI 1.65-10.01), respectively. Urinary
      cadmium (U-Cd), urinary mercury (U-Hg), age, occupation, hypertension, and
      diabetes had a significant association with higher U-NAG levels. However, blood
      lead (B-Pb), sex, and smoking were not associated with higher U-NAG. Especially,
      concurrent exposure to heavy metals (U-Hg or/and U-Cd) and air pollution had an
      additive adverse effect. In the group with both 4th quartile heavy metal exposure
      (U-Cd or/and U-Hg) and air pollution exposure, the OR in MEG-R and MEG-D was 6.49
      (95 % 1.42-29.65) and 8.12 (95 % CI 1.74-37.92), respectively, after adjustment
      for age, occupation, hypertension, diabetes. CONCLUSIONS: U-NAG levels seem to be
      affected by air pollution exposure as well as age, hypertension, diabetes, and
      even low levels of cadmium and low levels of mercury. Moreover, concurrent
      exposure to heavy metals and air pollution can have additive cytotoxic renal
      effects.

PMID- 27708789
TI  - Welcome to Nursing Open.

PMID- 27708786
TI  - Is there potential for the future provision of triage services in community
      pharmacy?
AB  - BACKGROUND: Worldwide the demands on emergency and primary health care services
      are increasing. General practitioners and accident and emergency departments are
      often used unnecessarily for the treatment of minor ailments. Community pharmacy
      is often the first port of call for patients in the provision of advice on minor
      ailments, advising the patient on treatment or referring the patient to an
      appropriate health professional when necessary. The potential for community
      pharmacists to act as providers of triage services has started to be recognised,
      and community pharmacy triage services (CPTS) are emerging in a number of
      countries. This review aimed to explore whether key components of triage services
      can be identified in the literature surrounding community pharmacy, to explore
      the evidence for the feasibility of implementing CPTS and to evaluate the
      evidence for the appropriateness of such services. METHODS: Systematic searches
      were conducted in MEDLINE, EMBASE and International Pharmaceutical Abstracts
      (IPA) databases from 1980 to March 2016. RESULTS: Key elements of community
      pharmacy triage were identified in 37 studies, which were included in the review.
      When a guideline or protocol was used, accuracy in identifying the presenting
      condition was high, with concordance rates ranging from 70 % to 97.6 % between
      the pharmacist and a medical expert. However, when guidelines and protocols were
      not used, often questioning was deemed insufficient. Where other health
      professionals had reviewed decisions made by pharmacists and their staff, e.g.
      around advice and referral, the decisions were considered to be appropriate in
      the majority of cases. Authors of the included studies provided recommendations
      for improving these services, including use of guidelines/protocols, education
      and staff training, documentation, improving communication between health
      professional groups and consideration of privacy and confidentiality. CONCLUSION:
      Whilst few studies had specifically trialled triage services, results from this
      review indicate that a CPTS is feasible and appropriate, and has the potential to
      reduce the burden on other healthcare services. Questions still remain on issues
      such as ensuring the consistency of the service, whether all pharmacies could
      provide this service and who will fund the service.

PMID- 27708790
TI  - An integrative review of the characteristics of meaningful learning in healthcare
      professionals to enlighten educational practices in health care.
AB  - AIM: Knowledge does not transfer automatically, but requires an active, personal
      progress through meaningful learning. As posited by the constructivist paradigm,
      the aim of this study was to identify the characteristics of meaningful learning
      by analysing definitions and correlated methods found in the literature. DESIGN:
      An integrative review. METHODS: Articles were sought on MEDLINE, CINAHL and
      SCOPUS; no language, time or study-design restrictions were adopted. Only papers
      referring explicitly to the diverse types of learning were taken into account; 11
      articles were included in this review. RESULTS: Findings from the literature
      revealed three different types of meaningful learning: (1) meaningful learning as
      'active building-up process'; (2) meaningful learning as 'change'; 3-meaningful
      learning as 'outcome of experience'. A focus on constructivism and meaningful
      learning provides a new outlook on healthcare professionals in learning,
      including nurses, who are gradually taking on greater responsibility in self- and
      ongoing education.

PMID- 27708788
TI  - A randomized, open-label pilot of the combination of low-level laser therapy and
      lorcaserin for weight loss.
AB  - BACKGROUND: Obesity is a significant public health problem and innovative
      treatments are needed. The purpose of this pilot study was to assess the
      preliminary efficacy and safety of a combined treatment of low-level laser
      therapy (LLLT) and lorcaserin on weight loss, health quality of life (QOL)
      measures, and cardiovascular risk factors. METHODS: Forty-five overweight and
      obese adult participants with a body mass index (BMI) >26.9 and <40 were
      randomized to receive LLLT, lorcaserin, or a combination of the two therapies.
      All study participants received treatment for 3 months and were followed for 3
      months post-treatment. Participants were recruited from June 2014 through
      September 2014. RESULTS: The majority of the 44 participants accrued to this
      study were female (84 %) with an average age of 43.9 years (range 22 to 64
      years). Most participants (93 % LLLT alone, 87 % LLLT + lorcaserin) completed at
      least 80 % of the LLLT treatments. From baseline to end of treatment, significant
      reductions in waist circumference were noted for each treatment group (-2.3 +/-
      4.1 cm, -6.0 +/- 7.3 cm, and -4.0 +/- 5.5 cm for LLLT, lorcaserin and combination
      respectively); however, the reduction in body weight was only significant in
      those receiving lorcaserin and combination treatment (-0.4 +/- 1.5 kg, -1.3 +/-
      1.2 kg and -1.3 +/- 1.3 kg). No significant differences were noted between the
      groups. Self-reported satisfaction was higher in the lorcaserin versus the LLLT
      group. CONCLUSION: This small pilot demonstrates that when combined with
      behavioral intervention, Lorcaserin and LLLT may be effective components of a
      comprehensive approach to the treatment of overweight and obesity in the clinical
      setting. Further studies with larger sample size and longer duration of treatment
      and follow-up are needed to further address efficacy. TRIAL REGISTRY INFORMATION:
      Trial registration: NCT02129608. Registered June 15, 2014.

PMID- 27708791
TI  - A secondary data analysis of Internet use in caregivers of persons with dementia.
AB  - AIM: This paper is a secondary data analysis to investigate relationships among
      caregiver stress appraisal, self-rated health and health-related Internet use.
      DESIGN: Cross-sectional correlation design. METHODS: National Alliance for
      Caregiving telephone survey conducted in the USA was a primary data source
      collected in 2009 from 258 caregivers of persons with dementia, who used the
      Internet to perform care-giving tasks. Based on Pearlin's Stress Process Model,
      structural equation modelling was conducted. RESULTS: Caregivers with poor health
      reported higher levels of caregiver stress appraised, which was associated with
      more Internet use for health-related purposes. It is required to develop
      effective Internet-based resources to meet the needs of highly stressed
      caregivers of persons with dementia. However, there was no relationship between
      self-rated health and health-related Internet use in dementia caregiver.

PMID- 27708792
TI  - Measurement of factors that negatively influence the outcome of quitting smoking
      among patients with COPD: psychometric analyses of the Try To Quit Smoking
      instrument.
AB  - AIMS: To test internal consistency and factor structure of a brief instrument
      called Trying to Quit smoking. BACKGROUND: The most effective treatment for
      patients with chronic obstructive pulmonary disease is to quit smoking. Constant
      thoughts about quitting and repeated quit attempts can generate destructive
      feelings and make it more difficult to quit. DESIGN: Development and psychometric
      testing of the Trying to Quit smoking scale. METHODS: The Trying to Quit smoking,
      an instrument designed to assess pressure-filled states of mind and corresponding
      pressure-relief strategies, was tested among 63 Swedish patients with chronic
      obstructive pulmonary disease. Among these, the psychometric properties of the
      instrument were analysed by Exploratory Factor Analyses. RESULTS: Fourteen items
      were included in the factor analyses, loading on three factors labelled: (1)
      development of pressure-filled mental states; (2) use of destructive pressure
      relief strategies; and (3) ambivalent thoughts when trying to quit smoking. These
      three factors accounted for more than 80% of the variance, performed well on the
      Kaiser-Meyer-Olkin (KMO) test and had high internal consistency.

PMID- 27708793
TI  - Understanding the perceptions and experiences of Certified Registered Nurse
      Anaesthetists regarding handovers: a focus group study.
AB  - AIM: The aim of this exploratory study was to gain further insight into the
      perceptions and experiences of Certified Registered Nurse Anaesthetists regarding
      intraoperative handovers of care. BACKGROUND: Handovers of care often result in
      adverse events in hospitalized patients and this risk is increased in the
      operating room setting where handovers occur frequently. Handovers between nurse
      anaesthetists, who provide the majority of anaesthesia in the United States
      today, is under-researched. DESIGN: Focus groups with Certified Registered Nurse
      Anaesthetists. METHODS: Two groups of nurse anaesthetists were recruited to
      participate in focus groups exploring their perception and experiences with
      intraoperative handovers of care. Content analysis was used to construe meaning
      from the context of the interviews. The findings were interpreted and discussed
      in a framework of Relationship-Based Care. FINDINGS: There were four main themes
      that emerged from the data: (1) characteristics of the setting are a threat to
      handover quality; (2) individual provider characteristics have an impact on
      handover quality; (3) The timing of the handover represents a threat to handover
      quality and (4) individual patient characteristics have an impact on handover
      quality. CONCLUSION: The specific threats to safe handover of care between nurse
      anaesthetists were perceived to fall into four major themes; this provides
      information needed to strengthen the environment of care and to improve safety in
      handover of care in the operating suite.

PMID- 27708794
TI  - A nurse-led intervention study: Promoting compliance with Diskus Inhaler use in
      asthma patients.
AB  - AIM: To examine the impact of a nurse-led patient assessment and education
      programme in promoting compliance with inhaler use in asthma patients. DESIGN: A
      quasi-experimental pre-test and post-test design. METHODS: A sample of asthmatic
      patients (N = 21) were recruited from the population of patients attending an
      asthma clinic. An Inhaler Proficiency Schedule (IPS) was developed and validated.
      At each visit, participants were requested to demonstrate their inhaler
      technique. The participants were investigated as to their confidence level with
      self-administration of their inhaler and adherence to prescribed doses. This
      information was recorded on a Patient-Reported Behaviour (PRB) questionnaire.
      RESULTS: Technique, compliance and patient confidence levels improved with nurse
      led education repeated over three visits; this was sustained on measurement at 6
      months following completion of the education programme.

PMID- 27708795
TI  - What's different about Nursing Open?

PMID- 27708797
TI  - A prospective observational study of machine translation software to overcome the
      challenge of including ethnic diversity in healthcare research.
AB  - AIM: This study investigates whether machine translation could help with the
      challenge of enabling the inclusion of ethnic diversity in healthcare research.
      DESIGN: A two phase, prospective observational study. METHODS: Two machine
      translators, Google Translate and Babylon 9, were tested. Translation of the
      Strengths and Difficulties Questionnaire (SDQ) from 24 languages into English and
      translation of an English information sheet into Spanish and Chinese were quality
      scored. Quality was assessed using the Translation Assessment Quality Tool.
      RESULTS: Only six of the 48 translations of the SDQ were rated as acceptable, all
      from Google Translate. The mean number of acceptably translated sentences was
      higher (P = 0.001) for Google Translate 17.1 (sd 7.2) than for Babylon 9 11 (sd
      7.9). Translation by Google Translate was better for Spanish and Chinese,
      although no score was in the acceptable range. Machine translation is not
      currently sufficiently accurate without editing to provide translation of
      materials for use in healthcare research.

PMID- 27708796
TI  - A qualitative exploration of nurses leaving nursing practice in China.
AB  - AIM: This paper reports a theoretical understanding of nurses leaving nursing
      practice by exploring the processes of decision-making by registered nurses in
      China on exiting clinical care. BACKGROUND: The loss of nurses through their
      voluntarily leaving nursing practice has not attracted much attention in China.
      There is a lack of an effective way to understand and communicate nursing
      workforce mobility in China and worldwide. DESIGN: This qualitative study draws
      on the constant comparative method following a grounded theory approach. METHOD:
      In-depth interviews with 19 nurses who had left nursing practice were
      theoretically sampled from one provincial capital city in China during August
      2009-March 2010. RESULTS: The core category 'Mismatching Expectations: Individual
      vs. Organizational' emerged from leavers' accounts of their leaving. By
      illuminating the interrelationship between the core category and the main
      category 'Individual Perception of Power,' four nursing behaviour patterns were
      identified: (1) Voluntary leaving; (2) Passive staying; (3) Adaptive staying and
      (4) Active staying.

PMID- 27708798
TI  - A scoping review of family experience and need during end of life care in
      intensive care.
AB  - AIM: To scope systematically and collate qualitative studies on family experience
      and need during end of life care in intensive care, from the perspective of
      family members. DESIGN: Scoping review of qualitative research. METHODS:
      Standardized processes of study identification, data extraction and data
      synthesis were used. Multiple bibliographic databases were accessed during 2011
      and updated in 2013. RESULTS: From an initial 876 references, 16 studies were
      identified for inclusion. These were predominantly single site, North American
      studies that explored issues relating to the temporal stages in the end of life
      trajectory and the requirement for information and emotional support at end of
      life. With a strong focus on family need and experience during the transition
      from active treatment to end of life care, more work is required to understand
      how doctors and nurses can support families from treatment withdrawal through to
      death.

PMID- 27708800
TI  - Ethics and open access.

PMID- 27708799
TI  - The significance of communities of practice: Norwegian nursing students'
      experience of clinical placement in Bangladesh.
AB  - AIM: The purpose of this study was to gain understanding of Norwegian students'
      experience of learning in clinical placement in Bangladesh without formal one-to
      one supervision, by a personal mentor in the ward. DESIGN: Using focus group
      interviews with bachelor nursing students we explored the significance of
      'communities of practice' in nursing practicum abroad, socialization and
      knowledge transfer. METHOD: Seven third year bachelor nursing students enrolled
      in a clinical placement programme in Bangladesh participated in focus group
      interviews prior to their departure to Bangladesh, during their stay in
      Bangladesh and after their return to Norway. RESULTS: The Students' marginality
      and 'peripheral participation' triggered insight and reflection. The challenging
      but advantageous position of the peripheral students was heightened further due
      to the lack of one-to-one supervision in the clinic. Their previous experience
      with problem based learning and group learning was an asset that made them more
      resilient and helped them to cope.

PMID- 27708801
TI  - Generation Y New Zealand Registered Nurses' views about nursing work: a survey of
      motivation and maintenance factors.
AB  - AIM: The aim of this article was to report on the analysis of qualitative, open
      text data, received from a national on-line survey of what factors Generation Y
      New Zealand Registered Nurses wish to change about nursing and consideration of
      the potential policy and practice impacts of these requests on their retention.
      BACKGROUND: Prior to the economic recession of 2007-2010, the growing shortage of
      nurses in New Zealand presented a serious concern for the healthcare workforce.
      Given the ageing New Zealand nursing workforce, an ageing population and the
      increasing demands for health care, it is imperative that issues of retention of
      Generation Y nurses are resolved prior to the imminent retirement of more
      experienced nurses. DESIGN: A descriptive exploratory approach using a national
      wide, on-line survey, eliciting both quantitative and qualitative data was used.
      METHOD: The survey, conducted from August 2009-January 2010, collected data from
      Generation Y New Zealand Registered Nurses (n = 358) about their views about
      nursing, work and career. Herzberg's Motivation-Hygiene theory was used as the
      framework for the analysis of the open text data. RESULTS: The factors that
      nurses wanted changed were skewed towards Herzberg's hygiene-maintenance factors
      rather than motivating factors. This is of concern because hygiene-maintenance
      factors are considered to be dissatisfiers that are likely to push workers to
      another employment option.

PMID- 27708802
TI  - A survey of the breast care nurse role in the provision of information and
      supportive care to Australian women diagnosed with breast cancer.
AB  - AIM: To explore the role of the Australian breast care nurse in the provision of
      information and support to women with breast cancer, with a focus on the
      differences experienced depending on geographic work context. DESIGN: A cross
      sectional study. METHODS: This study conducted in 2013, involved surveying BCNs
      currently working in Australia, using a newly developed self-report online
      survey. RESULTS: Fifty breast care nurses completed the survey, 40% from major
      cities, 42% from inner regional Australia and 18% from outer regional, remote and
      very remote Australia. Patterns of service indicated higher caseloads in urban
      areas, with fewer kilometres served. Breast care nurses in outer regional, remote
      and very remote areas were less likely to work in multi-disciplinary teams and
      more likely to spend longer consulting with patients. Breast care nurses reported
      they undertook roles matching the competency standards related to the provision
      of education, information and support; however, there were barriers to fulfilling
      competencies including knowledge based limitations, time constraints and
      servicing large geographical areas. CONCLUSIONS: This was the first Australian
      study to describe the role of the breast care nurse nationally and the first
      study to investigate breast care nurses perceived ability to meet a selection of
      the Australian Specialist Breast Nurse Competency Standards. Important
      differences were found according to the geographical location of breast care
      nurses.

PMID- 27708803
TI  - Using principal components analysis to explore competence and confidence in
      student nurses as users of information and communication technologies.
AB  - AIM: To report on the relationship between competence and confidence in nursing
      students as users of information and communication technologies, using principal
      components analysis. DESIGN: In nurse education, learning about and learning
      using information and communication technologies is well established. Nursing
      students are one of the undergraduate populations in higher education required to
      use these resources for academic work and practice learning. Previous studies
      showing mixed experiences influenced the choice of an exploratory study to find
      out about information and communication technologies competence and confidence. A
      48-item survey questionnaire was administered to a volunteer sample of first- and
      second-year nursing students between July 2008-April 2009. The cohort (N = 375)
      represented 18.75% of first- and second-year undergraduates. A comparison between
      this work and subsequent studies reveal some similar ongoing issues and ways to
      address them. METHODS: A principal components analysis (PCA) was carried out to
      determine the strength of the correlation between information and communication
      technologies competence and confidence. The aim was to show the presence of any
      underlying dimensions in the transformed data that would explain any variations
      in information and communication technologies competence and confidence.
      Cronbach's alpha values showed fair to good internal consistency. RESULTS: The
      five component structure gave medium to high results and explained 44.7% of the
      variance in the original data. Confidence had a high representation. The findings
      emphasized the shift towards social learning approaches for information and
      communication technologies. Informal social collaboration found favour with
      nursing students. Learning through talking, watching and listening all play a
      crucial role in the development of computing skills.

PMID- 27708804
TI  - The repositioning of hospitalized patients with reduced mobility: a prospective
      study.
AB  - AIM: To determine the frequency of patient repositioning across three consecutive
      nursing shifts (day, evening and night) and to identify predictors of
      repositioning frequency. BACKGROUND: Patient repositioning is a frequently
      implemented pressure injury prevention strategy. Yet, little is known about how
      often it should be implemented, or the frequency of movement among hospitalized
      patients with reduced mobility. DESIGN: An observational prospective study.
      METHODS: Chart audits were used to gather clinical and demographic data. Semi
      structured observations were conducted every 30 minutes for a continuous 24-hour
      period. Observational data included the patient's body position, the frequency of
      repositioning, assistance require to reposition and the use of support surfaces.
      RESULTS: Patients were repositioned frequently during the day and evening and
      least at night time. Elevation of the head of the bed (1-45 degrees ) was the
      most frequently adopted position. The independent predictors of repositioning
      frequency were age and gender, with older patients and males repositioned less
      frequently.

PMID- 27708805
TI  - Hijackers on the open access highway.

PMID- 27708806
TI  - "I know exactly what I'm going into": recommendations for pre-nursing experience
      from an evaluation of a pre-nursing scholarship in rural Scotland.
AB  - AIM: To develop a model of pre-nursing experience from evaluation of a pre
      nursing scholarship for school pupils in Scotland. DESIGN: Action research study.
      METHODS: School pupils (n = 42) completed questionnaire surveys and participated
      in anecdote circles. Student nurses acting as pupil 'buddies' (n = 33)
      participated in focus groups. Descriptive quantitative data and thematic analyses
      of qualitative data were integrated across cohorts and campuses. RESULTS: Ten
      recommended components of a model of pre-nursing experience were identified:
      educational experience of: (1) face-to-face on-campus teaching; (2) hands-on
      clinical skills sessions; and (3) andragogy, practice exposure to (4) nursing
      language; (5) nurses' emotional labour; (6) patients' stories; (7) pupils
      socializing with buddies; (8) buddies planning placement activities; and (9)
      supporting pupils during placements. Academic attainment was not a central
      component of the model due to pupils' need to (10) prioritize examined work for
      further/higher education entry.

PMID- 27708807
TI  - A qualitative study of professional caregivers' perceptions of processes
      contributing to mealtime agitation in persons with dementia in nursing home wards
      and strategies to attain calmness.
AB  - AIM: Describe professional caregivers' perceptions of factors and processes
      contributing to mealtime agitation and strategies for attaining and maintaining
      calm mealtimes. DESIGN: Qualitative and descriptive. METHODS: A convenience
      sample of professional caregivers working in two wards for residents with
      dementia was used. Data were collected during two focus-group interviews and
      supplemented with field notes from six reflection groups. Thematic content
      analysis was conducted. Data collection occurred from 2010-2011. RESULTS:
      Professional caregivers perceived agitation during mealtime as resulting from
      negative feelings in residents triggered by a lack of or negative social
      interaction, too much or ambiguous stimuli or demands exceeding residents'
      capacity. Strategies for attaining calm mealtimes involved thorough planning
      beforehand. During mealtime, professional caregivers focused on establishing a
      positive community around the table, helping residents focus on eating and
      continuously observing residents for subtle signals indicating that agitation was
      about to develop. The prerequisites to succeed with the strategies were knowledge
      of the residents' preferences and abilities, knowledge sharing within the team
      and awareness of one's own communication style. Thus, the professional caregivers
      operationalized person-centred care in a mealtime context.

PMID- 27708808
TI  - Managing perturbations during handover meetings: a joint activity framework.
AB  - AIM: To document the prevalence of perturbations of handover meetings and
      understand how nurses manage temporal, physical and social meeting boundaries in
      response to perturbations. BACKGROUND: Handovers are joint activities performed
      collaboratively by participating nurses. Perturbations of handover are frequent
      and may potentially threaten continuity of care. DESIGN: We observed and
      videotaped handovers during five successive days in four nursing care units in
      two Swiss hospitals in 2009. METHODS: Videorecordings were transcribed. All
      perturbations during the handovers were noted. We performed content analysis of
      the sources of perturbations from the notes and interactional micro-analyses of
      handover interactions based on video and transcripts. RESULTS: Nurses are the
      most frequent sources of perturbations during handovers. Perturbations are
      collaboratively managed. A tacit division of labour is enacted via multimodal
      communication strategies, whereby perturbations are dealt with using both
      linguistic and bodily signals.

PMID- 27708809
TI  - Pragmatism and integrated knowledge translation: exploring the compatabilities
      and tensions.
AB  - AIM: This paper presents a discussion of the role of the philosophy of pragmatism
      in the integrated knowledge translation approach to research. DESIGN: Critical
      inquiry is used to discuss bringing pragmatic philosophy and the integrated
      knowledge translation approach to research together to advance nursing knowledge.
      METHODS: This paper draws from the literature written on the philosophy of
      pragmatism and from the current literature on knowledge translation. The
      possibilities, tensions and limitations for underpinning an integrated knowledge
      translation research approach with pragmatic philosophy are discussed while
      highlighting the implications this has for creating knowledge aimed at advancing
      the practice of nursing. RESULTS: The implications for how nursing knowledge is
      created in using an integrated knowledge translation approach that is underpinned
      by pragmatic philosophy are important. Creating nursing knowledge that address
      the complex problems found in nursing practice is needed. In acknowledging the
      inseparability of knowledge and practice, researchers, practitioners, policy
      makers and the public can come together to co-create knowledge that is useful for
      the practice of nursing. It is these implications of underpinning an integrated
      knowledge translation research approach with pragmatic philosophy that are
      significant in creating nursing knowledge that advances the practice of nursing.

PMID- 27708810
TI  - Looking back on 2 years of Nursing Open: looking forward.

PMID- 27708811
TI  - Mary Seacole and claims of evidence-based practice and global influence.
AB  - AIM: The aim of this paper was to explore the contribution of Mary Seacole to
      nursing and health care, notably in comparison with that of Florence Nightingale.
      BACKGROUND: Much information is available, in print and electronic, that presents
      Mary Seacole as a nurse, even as a pioneer nurse and leader in public health
      care. Her own memoir and copious primary sources, show rather than she was a
      businesswoman, who gave assistance during the Crimean War, mainly to officers.
      Florence Nightingale's role as the major founder of the nursing profession, a
      visionary of public health care and key player in advocating 'environmental'
      health, reflected in her own Notes on Nursing, is ignored or misconstrued.
      DESIGN: Discussion paper. DATA SOURCES: British newspapers of 19th century and
      The Times digital archive; Australian and New Zealand newspaper archives,
      published memoirs, letters and biographies/autobiographies of Crimean War
      participants were the major sources. RESULTS: Careful examination of primary
      sources, notably digitized newspaper sources, British, Australian and New
      Zealand, show that the claims for Seacole's 'global influence' in nursing do not
      hold, while her use of 'practice-based evidence' might better be called self
      assessment. Primary sources, moreover, show substantial evidence of Nightingale's
      contributions to nursing and health care, in Australia, New Zealand, the USA and
      many countries and the UK much material shows her influence also on hospital
      safety and health promotion.

PMID- 27708812
TI  - A mixed-method study of pain management practice in a UK children's hospital:
      identification of barriers and developing strategies to maintain effective in
      patient paediatric pain management.
AB  - AIM: To assess Acute Pain Service and paediatric pain management efficacy in a UK
      specialist paediatric hospital to inform wider recommendations for future
      sustainability. BACKGROUND: UK paediatric acute pain services vary. Although
      comprehensive pain management guidelines exist, consensus on the best model of
      care is lacking. Worldwide, medical and pharmacological advances and rapid
      patient turnover have increased the challenges of managing hospitalized
      children's pain. Simultaneously nurses, who deliver the bulk of pain management,
      have experienced reduction in skill mix and training opportunities. Specialist
      Acute Pain Services have evolved to meet these demands; their overall efficacy is
      unknown. DESIGN: This mixed-methods study explores pain management practice at a
      UK paediatric hospital to assess current efficacy and future sustainability.
      METHOD: A 2013 case note review of all Acute Pain Services referrals over 14 days
      were compared with an interval sample of concurrent non-referred inpatient
      children; seven semi-structured interviews were conducted with a range of
      clinical staff. RESULTS: Twenty-two referrals of 15 children were made; 15
      comparison children were identified. All 30 children (100%) were appropriately
      referred/non-referred. Acute Pain Services cases experienced higher pain levels,
      were more likely to have long term conditions, longer hospital stay and repeat
      admissions. Three key themes emerged through interview analysis: 'addressing
      pain', 'changing contexts' 'pain as an "expert" skill'. Increased specialization,
      reduced clarity between different pain modalities and decreased training
      opportunities had resulted in potentially unsustainable APS dependence.

PMID- 27708813
TI  - Developing an instrument to self-evaluate the Discharge Planning of Ward Nurses.
AB  - AIMS: To develop the Discharge Planning of Ward Nurses (DPWN), a Japanese self
      evaluation instrument for ward nurses' discharge planning practices. DESIGN:
      Cross-sectional survey. METHODS: Participants were 624 ward nurses from six
      hospitals in Japan with a discharge planning department. Items about discharge
      planning practices were collected from literature and interviews with nurses and
      researchers. Construct validity, concurrent validity, internal consistency and
      test-retest reliability were tested. RESULTS: Initially, 55 items were collected.
      Examination of the floor effect, item-total, good-poor analyses and exploratory
      factor analysis yielded a four-factor model with 24 items ('teaching home-care
      skills with community/hospital professionals,' 'identifying clients' potential
      needs early in the discharge process,' 'introducing social resources' and
      'identifying client/family wishes and building consensus for discharge'). The
      four-factor structure was supported by confirmatory factor analysis. The DPWN
      correlated with scales ascertaining similar concepts, supporting concurrent
      validity. Internal consistency and test-retest reliability were generally
      satisfactory.

PMID- 27708814
TI  - Patient perceptions of nurse mentors facilitating the Aussie Heart Guide: A home
      based cardiac rehabilitation programme for rural patients.
AB  - AIM: To explore and describe long-term thoughts and perceptions of the Aussie
      Heart Guide Programme including the role of the mentor, held by patients
      recovering from myocardial infarction. DESIGN: A qualitative design. METHODS:
      Thirteen patients recovering from myocardial infarction who were unable to attend
      a hospital-based or affiliated outpatient cardiac rehabilitation programme were
      interviewed by telephone at the completion of the programme and asked to describe
      the relationship with their assigned nurse mentor and their perception of the
      audiovisual used in the programme. RESULTS: Three themes emerged; assisting me to
      cope, supporting me and my family and tailoring the programme to my needs.
      Patients were satisfied with the programme and appreciative of the supportive and
      caring relationships provided by mentors during their hospitalization through to
      their discharge from the programme.

PMID- 27708816
TI  - Beyond open access.

PMID- 27708815
TI  - Caregiver Contribution to Heart Failure Self-Care (CACHS).
AB  - AIM: While caregivers (CGs) make an important contribution to the self-care of
      heart failure (HF) patients, there are no reliable and valid tools for measuring
      such contributions. Current interventions that strive to optimize patient
      outcomes through self-care strategies neglect to account for CG contributions, a
      potential confounder on outcomes. The aim of the study was to develop an
      instrument that measures CG contributions to HF patients' self-care. DESIGN: The
      study design follows an established process for instrument development. METHODS:
      A systematic literature review and semi-structured interviews of CGs were
      conducted to identify measureable CG activities. Items were derived from thematic
      analysis of CG narratives. A content validity index was computed for each item (I
      CVI). Items with an I-CVI of >0.70 were retained. Items with an I-CVI of 0.50
      0.70 were revised for clarification and items with an I-CVI <0.5 were discarded,
      except in instances where fulsome theoretical or empirical evidence supported
      their retention. RESULTS: 14 CGs completed interviews and 10 CGs with 4 expert
      nurses completed I-CVI testing. Major interview themes included arranging
      appointments, medication adherence, monitoring, coordinating care, encouraging
      independence and taking action. A total of 36 items were constructed and
      underwent I-CVI testing. Following I-CVI testing, 27 items were retained, seven
      items were retained after revision based on CG feedback and two items were
      removed. This newly developed 34-item questionnaire represents current
      literature, CGs' experiences, excellent I-CVI scores and ready for further
      psychometric testing.

PMID- 27708818
TI  - Factors associated with older people's independent living from the viewpoint of
      health and functional capacity: a register-based study.
AB  - AIM: The aim of this study was to identify factors associated with independent
      living of older people from the point of view of health and functional capacity.
      BACKGROUND: Living independently at home is major wish for older people but is
      depending on health and functional capacity among others. Objective and
      subjective assessments have been considered important in determining threats for
      independent living but both of these views have rarely included in the same
      study. DESIGN: Descriptive, cross-sectional register-based study was conducted.
      METHODS: Data were collected using the Health and Functional Capacity survey by
      identifying the factors of health examinations of a cohort (N = 292) of 75-year
      old's, born in 1936 (N = 388), in one Finnish medium-sized municipality in 2011.
      This study is part of the Functional Ageing project Kaste 2013. The data were
      analysed statistically by using descriptive analysis, cross-tabulation and
      logistic regression. RESULTS: Partly, different factors were associated with
      subjective and objective health and functional capacity showing wide range of
      individuality. Worsening subjective health was associated with worsened self
      assessment of life situation. Worsening subjective health threatens independent
      living. Factors statistically significantly associated with worsening subjective
      health were low physical activity, falls during the last 6 months, not managing
      heavy housework, being sometimes lonely or dejected, having diagnosed diseases or
      health problems and polypharmacy.

PMID- 27708817
TI  - An integrative review of the impact of mobile technologies used by healthcare
      professionals to support education and practice.
AB  - AIM: The aim of this study was to provide evidence of the impact of mobile
      technologies among healthcare professionals in education and practice settings.
      DESIGN: Integrative literature review. METHODS: Electronic databases including
      MEDLINE, CINAHL, PsycINFO, EMBASE, ERIC and Web of Science were searched for
      papers published between 2002-2012. Quantitative studies were critically
      evaluated based on Thomas et al.'s framework, while the consolidated criteria for
      reporting qualitative research was used to appraise the rigour of the qualitative
      studies. RESULTS: Seventeen quantitative and three qualitative studies were
      included. The findings suggest a largely positive influence of mobile
      technologies on various clinical practice and educational outcomes. However,
      robust evidence was limited. Use of mobile technologies in health care are
      associated with improvements in access to information, accuracy and efficiency,
      evidence-based decision making at the point of care and enhancement in
      performance, confidence and engagement in different contexts.

PMID- 27708819
TI  - Predictors of workplace violence among ambulance personnel: a longitudinal study.
AB  - AIM: To examine predictors of repeated confrontations with workplace violence
      among ambulance personnel, the proportion of exposure to potentially traumatic
      events that are aggression-related and to what extent personnel was able to
      prevent escalations. Although previous research assessed the prevalences among
      this group, little is known about predictors, to what extent PTE's are WPV
      related and their abilities to prevent escalations. DESIGN: A longitudinal study
      with a 6 months' time interval (N = 103). METHODS: At T1 demographics, workplace
      violence and potentially traumatic events in the past year, mental health,
      personality, handling of rules, coping and social organizational stressors were
      assessed. Confrontations with aggression were also examined at T2. RESULTS:
      Multivariate logistic regression analyses showed that only problems with
      superiors independently predicted repeated verbal aggression and that only the
      (absence of the) ability to compromise very easily predicted repeatedly being on
      guard and repeatedly confronted with any form of aggression. Due to very low
      prevalences, we could not examine predictors of repeated confrontations with
      physical aggression (N = 5) and serious threat (N = 7). A large majority reported
      that in most workplace violence cases they could prevent further escalations.
      About 2% reported a potentially traumatic event in the year before T1 that was
      WPV related and perceived as very stressful.

PMID- 27708820
TI  - Sources, incidence and effects of non-physical workplace violence against nurses
      in Ghana.
AB  - AIM: To document the incidence, sources and effects of workplace verbal abuse and
      sexual harassment against Ghanaian nurses. METHODS: A cross-sectional study was
      conducted in Ghana from 2013-2014 which surveyed 592 professional nurses and
      midwives working in public hospitals in Ghana using the health sector violence
      questionnaire. RESULTS: The majority of participants were females (80%). The
      average age of participants was 31.76 years and the average number of years
      practising as nurse was 7.38. Twelve per cent of the participants experienced at
      least one incident of sexual harassment and 52.2% were exposed to verbal abuse.
      The majority of perpetrators of sexual harassment were medical doctors (50%).
      Relatives of patients emerged as the most frequent verbal abusers (45.5%). Chi
      square test showed statistically significant associations between gender and
      workplace violence and between workplace violence and intention to quit the
      nursing profession. The effects of workplace violence ranged from having
      disturbing memories about the incident to being 'super alert' and vigilant.
      Establishing the incidence of workplace violence is a necessary step towards
      addressing the problem. It is concluded that educational programs must be
      designed for healthcare workers and the general public to foster awareness of the
      effects of workplace violence. Clear policies must also be instituted to address
      the problem.

PMID- 27708822
TI  - What are Altmetrics and why would anyone be interested?

PMID- 27708821
TI  - Using cognitive behaviour therapy to explore resilience in the life-stories of 16
      UK centenarians.
AB  - AIM: In 2010, we interviewed 16 UK centenarians about their lives and later
      published a paper on the socio-emotional aspects of positive ageing. We were
      struck by their ability to 'move on' from difficult situations which we
      recognized conceptually as 'resilience'. In the effort to understand aspects of
      resilience as portrayed in their stories, we re-examined their data. METHODOLOGY:
      In the original study, we used participatory action research (PAR) for its
      storytelling and group process components. Here, we re-examine data from the
      centenarians' life stories using a cognitive behavioural therapy (CBT) lens.
      DESIGN: We focused on the notion of resilience in the centenarians' stories
      guided by CBT insights to analyse and develop psychosocial interpretations.
      RESULTS: Resilience comprised the ability to frame difficult life events in
      positive terms, accept what cannot be changed, manage worry and anxiety
      effectively, develop psychological flexibility in the face of change and
      continually seek opportunities for growth and development. We suggest that these
      resilient behaviours may have contributed to positive ageing.

PMID- 27708823
TI  - What are health professionals' intentions toward using research and products of
      research in clinical practice? A systematic review and narrative synthesis.
AB  - AIM: To explore health professionals' intentional behaviour and what determines
      their intention to use products of research in clinical practice. BACKGROUND:
      Trying to get research and products of research into clinical practice is an
      enduring problem. A clearer picture is emerging as to how individual
      practitioners respond toward practical problems of changing clinical practice,
      but this does not include health professionals' intentions to use products of
      research and what influences their intentions. DESIGN: Systematic Review and
      Narrative Synthesis. DATA SOURCES: Five databases were searched systematically.
      This included BNI, HMIC, Psych INFO, CINHAL and MEDLINE; articles published in
      the English language only were included. REVIEW METHODS: PRISMA guidelines were
      used as a framework for structuring the review and methods of narrative synthesis
      to analyse study outcomes. RESULTS: Eighteen studies matched the final inclusion
      criteria. All studies used questionnaires to measure intention. Most studies
      involved Nurses or Physicians. Nurses' intentions were mostly influenced by their
      perceived ability to use guidelines in their practice. Physicians' intentions
      were often influenced by their perceptions of the usefulness and relevance of the
      guideline and peer pressure amongst the professional group. Practice habits, when
      added to intentional models were also predictive of intentional behaviour. In
      studies that compared intentions with behaviour, the level of intention often did
      not match self-report or actual behaviour.

PMID- 27708824
TI  - Effects of training on attitudes of psychiatric personnel towards patients who
      self-injure.
AB  - BACKGROUND: Improving attitudes of personnel towards self-injurious patients
      leads to better working alliance and contributes to better patient outcomes.
      Previous research into the improvement of these attitudes has recorded the need
      for specific training in evidence-based assessment and treatment of self
      injurious patients. AIM: The current study describes the attitudes towards self
      injurious patients among psychiatric personnel. The study also evaluates the
      effect of a structured clinical training program on psychiatric personnel's
      attitudes towards patients who self-injure. It further examines whether age,
      education, frequency of self-injurious patients contact, and work experience of
      the personnel are associated with the existing attitudes. METHODS: Psychiatric
      personnel (N = 50) attended a four-day training program, presenting evidence
      based knowledge regarding self-injury assessment and treatment, using group
      exercises and reflective learning principles. The personnel completed the
      Understanding Suicidal Patients Questionnaire (USP) anonymously PreTraining, on
      17 January 2014, and PostTraining, on 20 June 2014. The mean differences as well
      as single USP items before and after the training were tested by unpaired t-test.
      Two-way ANOVA was used to test impact of background variables on the USP scores.
      RESULTS: The training program had statistically significant impact (P < 0.01) on
      the following individual items of the USP scale: Patients who have tried to
      commit suicide are usually treated well in my work unit (d = 1.02); A person who
      has made several suicide attempt is at greater risk of committing suicide (d =
      0.64); Because the patients who have tried to commit suicide have emotional
      problems, they need the best possible treatment (d = 0.57). The results also
      suggested that the frequency of patient contact had impact on attitudes towards
      self-injurious patients.

PMID- 27708825
TI  - Characteristics of patients who are admitted with or acquire Pressure Ulcers in a
      District General Hospital; a 3 year retrospective analysis.
AB  - AIM: The study aimed to characterize demographic and clinical practice factors
      associated with community (CAPU) and hospital acquired pressure ulcers (HAPU).
      DESIGN: A comparative retrospective evaluation of pressure ulcer data, collected
      from a district general hospital. METHODS: Demographic and pressure ulcer related
      data were collected from patients at risk of developing a pressure ulcer,
      collated by a single observer using a standardized tool. Comparisons were made
      within and between patient groups (no PU, CAPU and HAPU). RESULTS: CAPU and HAPU
      patient groups were significantly (P < 0.001) older, had extended lengths of
      hospital stay and were less likely to be provided quickly with a pressure
      relieving support surface than those with no PU. HAPU patients had a longer
      length of stay and a higher proportion of heel PUs compared to CAPU.

PMID- 27708826
TI  - Nursing documentation of pressure ulcers in nursing homes: comparison of record
      content and patient examinations.
AB  - AIM: The aim of this study was to describe the accuracy and quality of nursing
      documentation of the prevalence, risk factors and prevention of pressure ulcers,
      and compare retrospective audits of nursing documentation with patient
      examinations conducted in nursing homes. DESIGN: This study used a cross
      sectional descriptive design. METHOD: A retrospective audit of 155 patients'
      records and patient examinations using the European Pressure Ulcer Advisory Panel
      form and the Braden scale, conducted in January and February 2013. RESULTS: The
      prevalence of pressure ulcers was 38 (26%) in the audit of the patient records
      and 33 (22%) in patient examinations. A total of 17 (45%) of the documented
      pressure ulcers were not graded. When comparing the patient examinations with the
      patient record contents, the patient records lacked information about pressure
      ulcers and preventive interventions.

PMID- 27708827
TI  - Surgical readmissions: results of integrating pre-, peri- and postsurgical care.
AB  - AIMS: To explore the feasibility of recruiting surgical oncology patients and
      implementing a surgical integrated discharge (SID) programme led by advanced
      practice providers (APP). BACKGROUND: Burden of illness and complexity of
      treatment regimen makes it challenging for surgical oncology patients to
      participate in research. Surgical oncology nurses may have the necessary
      expertise to overcome this problem. DESIGN: Controlled longitudinal prospective
      observational study. METHODS: The SID programme included multidisciplinary care
      coordination, regular communication among APPs and proactive postdischarge follow
      up. Administrative databases were used to identify matching historical controls
      (n = 113) and evaluate programme outcomes. RESULTS: Patient enrolment was 84%.
      The main challenges for the programme implementation included incompatible health
      information systems among care settings, variation in care processes among
      hospital units and need for provider behaviour change. CONCLUSIONS: Most surgical
      oncology patients are willing to participate in outcomes programmes when
      contacted by familiar clinical personnel but programme implementation requires
      leadership support, communication among care teams and training and
      infrastructure.

PMID- 27708829
TI  - Editorial.

PMID- 27708828
TI  - Shared decision-making on a 'life-and-care plan' in long-term care facilities:
      research protocol.
AB  - AIM: To determine whether the number of residents' preferences and needs together
      with the actions taken to satisfy them recorded into their 'life-and-care plans'
      will increase and the process of shared decision-making will improve the
      residents' psychosocial well-being. BACKGROUND: Shared decision-making is defined
      as a process where healthcare professionals and patients make decisions together,
      using the best available evidence. The aims of the present study were to assess
      the feasibility and acceptability of an SDM framework for care planning in long
      term care facilities and its potential effectiveness on the proportion of
      dementia residents whose own preferences and needs and the related actions, are
      known, satisfied and documented in their 'life-and-care plans'. DESIGN: The
      current project is a feasibility trial and it was approved in November 2013.
      METHODS: Research subjects are triads composed of the resident with dementia, a
      family caregiver and the professional usually taking care for the resident.
      Professional caregivers of two nursing homes, one located in Italy and one in the
      Netherlands, will receive a specific training in SDM principles and will guide
      the SDM interview in the triad. The primary outcome will be the proportion of
      residents whose preferences and needs, together with the related actions to meet
      them, are known, documented and satisfied in their 'life-and-care plans'. TRIAL
      REGISTRATION: NCT02118701.

PMID- 27708830
TI  - Peer review and the publication process.
AB  - AIMS: To provide an overview of the peer review process, its various types,
      selection of peer reviewers, the purpose and significance of the peer review with
      regard to the assessment and management of quality of publications in academic
      journals. DESIGN: Discussion paper. METHODS: This paper draws on information
      gained from literature on the peer review process and the authors' knowledge and
      experience of contributing as peer reviewers and editors in the field of health
      care, including nursing. RESULTS: There are various types of peer review: single
      blind; double blind; open; and post-publication review. The role of the reviewers
      in reviewing manuscripts and their contribution to the scientific and academic
      community remains important.

PMID- 27708831
TI  - Patient complaints about health care in a Swedish County: characteristics and
      satisfaction after handling.
AB  - AIM: To describe patient complaints and to examine possible associations between
      healthcare providers' statements and reports of satisfaction/dissatisfaction.
      DESIGN: A retrospective and descriptive design was used to examine filed
      complaints. METHODS: Complaints from one Patient Advisory Committee in Sweden in
      2011 was examined using three different protocols/reading guides (n = 618).
      Associations between contents in responses from healthcare providers and reports
      of satisfaction/dissatisfaction from the complainants were analysed. RESULTS:
      Less than one-third of the complainants were satisfied after handling and with
      healthcare providers' statements about the complaint. The most frequent causes
      for dissatisfaction were that the healthcare provider 'did not tell the truth' or
      'gave insufficient information'. There was a statistically significant
      association with dissatisfaction if the statement from the healthcare provider
      included the category 'disagree/defend themselves'. Four categories were
      associated with being satisfied and the associations were statistically
      significant when two or more of these were combined.

PMID- 27708833
TI  - Re-establishing and preserving hope of recovery through user participation in
      patients with a severe mental disorder: the self-referral-to-inpatient-treatment
      project.
AB  - AIMS: The treatment of patients with a severe mental disorder is generally not
      good enough. The aim of this article was to illustrate some alternative
      approaches for better understanding and treatment for the individual, besides
      seeing and interpreting the symptoms. METHODS: The context of understanding is
      regulation of emotions whit a person-based approach. The self-referral-to
      inpatient-treatment project is presented and discussed as a possible method of
      intervention to improve patient involvement. DESIGN: Theoretical approach.
      RESULTS: Involvement in genuine decisions, where the individual is in control and
      feels emotionally robust, is important. The experience of regaining authority
      through being self-empowered with sufficient environmental support is essential
      for re-establishing and preserving hope of recovery.

PMID- 27708832
TI  - Dispositional mindfulness and employment status as predictors of resilience in
      third year nursing students: a quantitative study.
AB  - BACKGROUND: Nursing students will graduate into stressful workplace environments
      and resilience is an essential acquired ability for surviving the workplace. Few
      studies have explored the relationship between resilience and the degree of
      innate dispositional mindfulness, compassion, compassion fatigue and burnout in
      nursing students, including those who find themselves in the position of needing
      to work in addition to their academic responsibilities. AIM: This paper
      investigates the predictors of resilience, including dispositional mindfulness
      and employment status of third year nursing students from three Australian
      universities. DESIGN: Participants were 240 undergraduate, third year, nursing
      students. Participants completed a resilience measure (Connor-Davidson Resilience
      Scale, CD-RISC), measures of dispositional mindfulness (Cognitive and Affective
      Mindfulness Scale Revised, CAMS-R) and professional quality of life (The
      Professional Quality of Life Scale version 5, PROQOL5), such as compassion
      satisfaction, compassion fatigue and burnout. METHOD: An observational
      quantitative successive independent samples survey design was employed. A
      stepwise linear regression was used to evaluate the extent to which predictive
      variables were related each to resilience. RESULTS: The predictive model
      explained 57% of the variance in resilience. Dispositional mindfulness subset
      acceptance made the strongest contribution, followed by the expectation of a
      graduate nurse transition programme acceptance, with dispositional mindfulness
      total score and employment greater than 20 hours per week making the smallest
      contribution. This was a resilient group of nursing students who rated high with
      dispositional mindfulness and exhibited hopeful and positive aspirations for
      obtaining a position in a competitive graduate nurse transition programme after
      graduation.

PMID- 27708834
TI  - Outcomes from a pilot psychological therapies service for UK military veterans.
AB  - AIM: To evaluate the outcomes of participants attending a psychological therapies
      service for military veterans. BACKGROUND: The UK Military Veterans' Improving
      Access to Psychological Therapies Service (North West) (MV IAPT) provided a
      clinical psychological therapies service for military veterans. Outcomes of
      depression, anxiety and social adjustment were assessed after treatment in the
      service's pilot phase. DESIGN: An observational, prospective cohort study
      examined changes in depression, anxiety and social adjustment during receipt of
      the service. METHODS: Changes in depression (PHQ-9), anxiety (GAD-7) and social
      adjustment (WSAS) were examined in 952 veterans referred over 20 months from
      September 2011. Data were collected using the IAPT clinical information system
      plus additional fields. Changes for patients who completed treatment, remained in
      treatment and dropped out were compared. RESULTS: Seven hundred and seven
      veterans received an initial assessment, from which 505 received two or more
      appointments. Of these, 156 completed treatments, 179 remained in treatment and
      170 dropped out. The majority of veterans had been operationally deployed and
      were similar in risk characteristics to those in other military cohort studies.
      There were highly significant improvements on all measures (p<.01), with
      completers improving more and having higher rates of recovery from depression and
      anxiety than those remaining and drop outs. Recovery rates compared favourably
      with evaluations of general IAPT services and also exceeded reported natural
      recovery rates.

PMID- 27708835
TI  - Validation of the Spanish version of the Edinburgh feeding evaluation in dementia
      scale applied to institutionalized older persons with dementia: a study protocol.
AB  - AIM: The aim of this study was to obtain a Spanish version of the Edinburgh
      Feeding Evaluation in Dementia Scale version, to assess its reliability for use
      by medical staff and caregivers at residential care homes, to evaluate by
      confirmatory methods its construct validity. A further aim was to determine the
      criterion validity with respect to biochemical markers of malnutrition such as
      serum albumin, transferrin, cholesterol and lymphocytes, the body mass index and
      the mini nutritional assessment. DESIGN: Clinimetric cross-validation study.
      METHODS: Institutionalized subjects with dementia will be observed while
      consuming meals and evaluated with the instrument independently by nurses and
      caregivers.

PMID- 27708838
TI  - Editorial.

PMID- 27708837
TI  - A novel predictive factor for the onset time of docetaxel-induced onychopathy: a
      multicenter retrospective study.
AB  - BACKGROUND: Taxanes are known to cause onychopathy. Previous studies have
      reported the relationship between onychopathy and paclitaxel dosing intervals and
      cumulative doses. However, there are no studies of the predictive factors for
      docetaxel-induced nail changes. The present study used the drug accumulation rate
      (mg/m2/day) as a novel indicator and evaluated its usefulness for the prediction
      of onychopathy. METHODS: From January 2008 to December 2009, we examined patients
      who received docetaxel at the Toyama University Hospital and Tonami General
      Hospital to determine the time to onset of onychopathy, the accumulation rate,
      and the cumulative dose. We then divided the study subjects into two groups, and
      used Receiver Operating Characteristic (ROC) analysis to calculate a cut-off
      value. We evaluated both indicators as predictive factors for onychopathy using
      the log-rank test and Cox proportional hazards model. RESULTS: Ninety-five
      patients were included in the present study. The results of the log-rank test sub
      analysis revealed that the median number of days until onychopathy onset was
      significantly shorter in patients with an accumulation rate greater than the cut
      off (P = 0.009), and in those with a cumulative dose below the cut-off (P <
      0.001). The hazard ratios for the accumulation rate and cumulative dose,
      evaluated using Cox proportional hazards regression analysis, were 1.44 (P =
      0.036) and 0.99 (P < 0.001), respectively. CONCLUSIONS: The results of the
      present study indicated that the drug accumulation rate influenced the time to
      onset of docetaxel-induced onychopathy. TRIAL REGISTRATION: This study is not
      applicable for trial registration due to retrospective chart review without
      intervention.

PMID- 27708839
TI  - Mediating effects of dietary intake on associations of TV viewing, body mass
      index and metabolic syndrome in adolescents.
AB  - OBJECTIVE: Evidence suggests that TV viewing is associated with body mass index
      (BMI) and metabolic syndrome (MetS) in adolescents. However, it is unclear
      whether dietary intake mediates these relationships. METHODS: A cross-sectional
      analysis was conducted in adolescents (12-19 years) participating in the 2003
      2006 United States National Health and Nutrition Examination Survey. BMI z scores
      (zBMI) (n = 3,161) and MetS (n = 1,379) were calculated using age- and sex
      specific criteria for adolescents. TV viewing (h/day) was measured via a self
      reported questionnaire, and dietary intake was assessed using two 24-h recalls.
      Using the MacKinnon method, a series of mediation analyses were conducted
      examining five dietary mediators (total energy intake, fruit and vegetable
      intake, discretionary snacks, sugar-sweetened beverages and diet quality) of the
      relationships between TV viewing and zBMI and MetS. RESULTS: Small positive
      relationships were observed between TV viewing and zBMI (beta = 0.99, p < 0.001)
      and TV viewing and MetS (OR = 1.18, p = 0.046). No dietary element appeared to
      mediate the relationship between TV viewing and zBMI. However, sugar-sweetened
      beverage consumption and fruit and vegetable intake partially mediated the
      relationship between TV viewing and MetS, explaining 8.7% and 4.1% of the
      relationship, respectively. CONCLUSIONS: These findings highlight the complexity
      of the relationships between TV viewing, dietary intake and cardiometabolic
      health outcomes, and that TV viewing should remain a target for interventions.

PMID- 27708840
TI  - Portion-size preference as a function of individuals' body mass index.
AB  - OBJECTIVE: Large portions of food are often blamed for rising rates of obesity.
      We tested the possibility that people who are heavier may tend to select or
      prefer larger portions than do people who are lighter. METHODS: Participants
      (total N = 798) were asked to choose between a small and larger portion of pasta
      for a hypothetical meal (Studies 1, 2 and 4), to indicate their ideal portion
      from a range of portion-size options (Study 2), or to select their preferred
      portion size from each of 28 portion pairs (Study 3). RESULTS: Across all
      studies, there were no significant differences between heavier and lighter
      participants in their portion-size selection (effect sizes ranged from d = -0.06
      to 0.33). The pattern was the same regardless of whether we grouped participants
      as having a body mass index (BMI) <25 vs. >=25, as having a BMI of <30 vs. >=30,
      or treated BMI as a continuous predictor. CONCLUSIONS: Given the lack of
      association between BMI and portion-size preference, we suggest that factors
      other than portion size, such as differences in meal frequency, food type, plate
      clearing or compensation at subsequent meals, may need to be considered in order
      to explain the increasing prevalence of obesity.

PMID- 27708836
TI  - Pathophysiology of sepsis-induced myocardial dysfunction.
AB  - Sepsis-induced myocardial dysfunction is a common complication in septic patients
      and is associated with increased mortality. In the clinical setting, it was once
      believed that myocardial dysfunction was not a major pathological process in the
      septic patients, at least in part, due to the unavailability of suitable clinical
      markers to assess intrinsic myocardial function during sepsis. Although sepsis
      induced myocardial dysfunction has been studied in clinical and basic research
      for more than 30 years, its pathophysiology is not completely understood, and no
      specific therapies for this disorder exist. The purpose of this review is to
      summarize our current knowledge of sepsis-induced myocardial dysfunction with a
      special focus on pathogenesis and clinical characteristics.

PMID- 27708841
TI  - Response to a standard behavioral weight loss intervention by age of onset of
      obesity.
AB  - BACKGROUND: The purpose of this study was to examine weight loss, physical
      activity, fitness and diet changes in response to a standard behavioral weight
      loss intervention in adults with self-reported juvenile onset (n = 61) or adult
      onset (n = 116) obesity. METHODS: Participants (n = 177; 43.0 +/- 8.6 years; body
      mass index [BMI] = 33.0 +/- 3.4 kg m-2) engaged in an 18-month standard
      behavioral weight loss intervention. Participants were randomized into three
      different intervention groups as part of the larger parent trial. BMI, physical
      activity, fitness and diet were assessed at baseline, 6, 12 and 18 months.
      Separate adjusted mixed models were constructed using SAS version 9.4 (SAS
      Institute, Cary, NC). RESULTS: There was significant weight loss, increased
      physical activity, improved fitness and reduced caloric intake over time (p <
      0.001). There were no significant differences in these outcome variables by
      obesity onset group. However, there was a significant group by time interaction
      for fitness (p = 0.001), with the adult onset making significantly greater gains
      in fitness from baseline to 6 months (p < 0.001); however, this difference was no
      longer present at 12 or 18 months. CONCLUSIONS: With the exception of fitness at
      6 months, weight loss, physical activity and diet did not differ between juvenile
      onset and adult onset participants, suggesting that those with juvenile onset
      obesity are equally responsive to a standard behavioral weight loss intervention
      in adulthood.

PMID- 27708842
TI  - Maximizing retention in long-term clinical trials of a weight loss agent: use of
      a dietitian support team.
AB  - OBJECTIVE: High-attrition rates have been observed in long-term clinical trials
      of weight loss agents. We evaluated the impact of an innovative retention
      programme on 1-year retention. METHODS: Three Phase 3 global multicentre clinical
      trials evaluated the efficacy and safety of a CB1 receptor antagonist in subjects
      with BMI >= or = 27 kg/m2. The impact of a multifaceted retention programme
      including a dietitian screening interview, a comprehensive culturally adapted
      lifestyle modification programme, and a dietitian support system to maximize
      lifestyle adherence, was evaluated in 4,410 subjects from four subpopulations
      (non-US English-speaking, non-English-speaking, US-without dietitian screening
      and US-with dietitian screening) comprising 208 centres from 15 countries.
      RESULTS: The median proportion retained over the first year among subjects in
      three protocols was 82%. Non-English-speaking countries showed higher retention
      rates (89%) compared with the USA (73%) and non-US English-speaking (81%)
      countries. Within the USA, behavioural screening was associated with 29%
      reduction in dropout rate; for every five monthly teleconferences attended above
      11, there was a 32% decrease in dropout rate. CONCLUSIONS: This novel retention
      programme greatly improved upon reported retention rates of studies conducted
      with other weight loss agents in long-term clinical trials. Its effectiveness
      should be confirmed in future trials.

PMID- 27708843
TI  - Current practices of obesity pharmacotherapy, bariatric surgery referral and
      coding for counselling by healthcare professionals.
AB  - INTRODUCTION: Rates of obesity pharmacotherapy use, bariatric surgery and
      intensive behavioural counselling have been extremely low. OBJECTIVES: The
      primary objective of this study was to survey healthcare provider beliefs,
      practice and knowledge regarding obesity management. METHODS: Primary care
      physicians (PCPs), OB-GYN physicians and nurse practitioners (NPs) responded to a
      web-based survey related to drug therapy practice, bariatric surgery referral and
      reimbursement coding practice. RESULTS: Rates of reported use of obesity
      pharmacotherapy appear to be increasing among PCPs, which is likely related to
      the approval of four new obesity pharmacotherapy agents since 2012. Rates of
      pharmacotherapy use among OB-GYNs and NPs appear much lower. Similarly, few PCPs
      are averse to recommending bariatric surgery, but aversion among OB-GYNs and NPs
      is significantly higher. CONCLUSION: Together, these observations suggest that OB
      GYN and NP populations are important targets for education about obesity
      management. Very few PCPs, OB-GYNs or NPs use behavioural counselling coding for
      obesity. Better understanding of why this benefit is not being fully used could
      inform outreach to improve counselling rates.

PMID- 27708845
TI  - Lifestyle modification interventions differing in intensity and dietary
      stringency improve insulin resistance through changes in lipoprotein profiles.
AB  - OBJECTIVE: Metabolic dysfunction characterized by insulin resistance (IR) is an
      important risk factor for type-2 diabetes and coronary artery disease (CAD). The
      aim of this study was to determine if clinical lifestyle interventions differing
      in scope and intensity improve IR, defined by the lipoprotein IR (LPIR) score, in
      individuals differing in the severity of metabolic dysfunction. METHODS: Subjects
      with diagnosed type-2 diabetes, CAD or significant risk factors participated in
      one of two clinical lifestyle modification interventions: (i) intensive non
      randomized programme with a strict vegetarian diet (n = 90 participants, 90
      matched controls) or (ii) moderate randomized trial following a Mediterranean
      style diet (n = 89 subjects, 58 controls). On-treatment and intention-to-treat
      analyses assessed changes over 1 year in LPIR, lipoprotein profiles and metabolic
      risk factors in intervention participants and controls in both programmes.
      RESULTS: In the on-treatment analysis, both interventions led to weight loss: [
      8.9% (95% CI, -10.3 to -7.4), intensive programme; -2.8% (95% CI, -3.8 to -1.9),
      moderate programme; adjusted P < 0.001] and a decrease in the LPIR score [-13.3%
      (95% CI, -18.2 to -8.3), intensive; -8.8% (95% CI, -12.9 to -4.7), moderate;
      adjusted P < 0.01] compared with respective controls. Of the six lipoprotein
      parameters comprising LPIR, only large very-low-density lipoprotein particle
      concentrations decreased significantly in participants compared with controls in
      both programmes [-26.3% (95% CI, -43.0 to -9.6), intensive; -14.2% (95% CI, -27.4
      to -1.0), moderate; P < 0.05]. Intention-to-treat analysis confirmed and
      strengthened the primary results. CONCLUSION: A stringent lifestyle modification
      intervention with a vegetarian diet and a moderate lifestyle modification
      intervention following a Mediterranean diet were both effective for improving IR
      defined by the LPIR score.

PMID- 27708844
TI  - Anthropometric predictors of body fat in a large population of 9-year-old school
      aged children.
AB  - OBJECTIVE: To develop and cross-validate predictive models for percentage body
      fat (%BF) from anthropometric measurements [including BMI z-score (zBMI) and calf
      circumference (CC)] excluding skinfold thickness. METHODS: A descriptive study
      was carried out in 3,084 pre-pubertal children. Regression models and neural
      network were developed with %BF measured by Bioelectrical Impedance Analysis
      (BIA) as the dependent variables and age, sex and anthropometric measurements as
      independent predictors. RESULTS: All %BF grade predictive models presented a good
      global accuracy (>=91.3%) for obesity discrimination. Both overfat/obese and
      obese prediction models presented respectively good sensitivity (78.6% and
      71.0%), specificity (98.0% and 99.2%) and reliability for positive or negative
      test results (>=82% and >=96%). For boys, the order of parameters, by relative
      weight in the predictive model, was zBMI, height, waist-circumference-to-height
      ratio (WHtR) squared variable (_Q), age, weight, CC_Q and hip circumference
      (HC)_Q (adjusted r2 = 0.847 and RMSE = 2.852); for girls it was zBMI, WHtR_Q,
      height, age, HC_Q and CC_Q (adjusted r2 = 0.872 and RMSE = 2.171). CONCLUSION:
      %BF can be graded and predicted with relative accuracy from anthropometric
      measurements excluding skinfold thickness. Fitness and cross-validation results
      showed that our multivariable regression model performed better in this
      population than did some previously published models.

PMID- 27708847
TI  - Lifestyle modification intervention improves glycemic control in Mongolian adults
      who are overweight or obese with newly diagnosed type 2 diabetes.
AB  - OBJECTIVE: To evaluate the effectiveness of a weight loss intervention in
      Mongolian adults with newly diagnosed type 2 diabetes mellitus and with BMIs >=
      25.0 kg/m2. METHODS: Eighty participants (33 men/47 women) aged 32-56 years old
      received education sessions to improve nutritional habits and increase physical
      activity. Participants were counselled in-person on two occasions with regular
      follow-up by phone to eat less (reduce calorie intake by 30-40% and consume fewer
      fatty foods), shift food intake to earlier in a day and increase physical
      activity such as walking, jogging, running and biking. Measurements were
      performed before and after the 6-month intervention. RESULTS: After 6 months, the
      average weight loss was 4.3 +/- 4.7 kg, representing a 4.9 +/- 5.4% reduction in
      body weight (p < 0.0001). Mean HbA1c decreased from 8.5 +/- 2.7% to 6.0 +/- 1.8%
      (p < 0.0001), and the percent of individuals with HbA1c in the diabetic range
      dropped from 76.3% to 27.5%. These changes were accompanied by marked
      improvements in cardiovascular risk factors, including total cholesterol (3.92 +/
      1.02 to 3.13 +/- 0.80 mmol/l; p < 0.0001) and triglycerides (2.11 +/- 0.82 to
      1.54 +/- 0.51 mmol/l; p < 0.0001), and modest reductions in systolic and
      diastolic blood pressure (p < 0.05). CONCLUSION: The remarkable improvement in
      glycemic control and lipid profile in participants suggests that a lifestyle
      modification intervention targeting weight loss may be highly effective for early
      diabetes treatment and prevention in Mongolians.

PMID- 27708846
TI  - Alternate-day versus daily energy restriction diets: which is more effective for
      weight loss? A systematic review and meta-analysis.
AB  - BACKGROUND: Alternate-day-fasting (ADF) has been proposed as an effective dieting
      method. Studies have found that it also can increase life span in rodents, and
      reduce inflammation in humans. The aim of this paper was to systematically review
      the efficacy of ADF compared to very-low-calorie dieting (VLCD) in terms of
      weight loss, and reduction of fat mass and fat-free mass. METHODS: Systematic
      review: PubMed literature searches were performed. Fixed review procedures were
      applied. Studies were evaluated for quality. Twenty-eight studies were included.
      Meta-analysis: 10/28 studies (four ADF and six matched VLCD) were further
      analyzed. RESULTS: After adjustment for BMI and duration, there was no
      significant difference in mean body weight loss (VLCD 0.88 kg more weight loss
      than ADF, 95% CI: -4.32, 2.56) or fat-free mass (VLCD 1.69 kg more fat-free mass
      loss than ADF, 95% CI: -3.62, 0.23); there was a significant difference observed
      in fat mass (ADF 3.31 kg more fat mass loss than VLCD, 95% CI: 0.05, 6.56). Meta
      analysis showed that, among ADF studies, the pooled change in body weight, fat
      mass and fat-free mass was 4.30 kg (95% CI: 3.41, 5.20), 4.06 kg (95% CI: 2.99,
      5.13) and 0.72 kg (95% CI: -0.07, 1.51), respectively, while among VLCD studies,
      the pooled change was 6.28 kg (95% CI: 6.08, 6.49), 4.22 kg (95% CI: 3.95, 4.50)
      and 2.24 kg (95% CI: 1.95, 2.52), respectively. CONCLUSIONS: Our results from
      both the systematic review and the meta-analysis suggest that ADF is an
      efficacious dietary method, and may be superior to VLCD for some patients because
      of ease of compliance, greater fat-mass loss and relative preservation of fat
      free mass. Head-to-head randomized clinical trials are needed to further assess
      relative efficacy of these two approaches.

PMID- 27708850
TI  - Facts and numbers on epidemiology and pharmacological treatment of heart failure
      with preserved ejection fraction.
AB  - Heart failure with preserved ejection fraction (HFpEF) is a major and growing
      public health problem. Epidemiologic studies demonstrated that heart failure (HF)
      can be clinically diagnosed in patients with normal or preserved left ventricular
      ejection fraction. These patients are therefore termed as having HFpEF. In the
      past, this was often called diastolic HF. Because of the permanent increase of
      the prevalence of HFpEF during the past decades, HFpEF now accounts for more than
      50% of the total HF population. There are uncertainties and debates regarding the
      definition, diagnosis, and pathophysiology with the consequence that all outcome
      trials performed so far used criteria for inclusion and exclusion that were not
      consistent. These trials also failed to document improved prognosis. Recent
      smaller proof-of-concept or Phase II clinical trials investigating different
      pathophysiological approaches with substances such as the neprilysin inhibitor
      angiotensin receptor blocker- combination (LCZ 696), ranolazine, or ivabradine
      were successful to improve biomarkers, haemodynamics, or functional capacity.
      Future trials will need to document whether also prognosis can be improved.

PMID- 27708849
TI  - Highly purified eicosapentaenoic acid ameliorates cardiac injury and adipose
      tissue inflammation in a rat model of metabolic syndrome.
AB  - INTRODUCTION: n-3 Polyunsaturated fatty acids such as eicosapentaenoic acid
      (EPA), which are abundant in fish oil, have been shown to delay the onset of
      cardiovascular events. We previously established DahlS.Z-Leprfa/Leprfa (DS/obese)
      rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats,
      as a model of metabolic syndrome. This study has now explored the influence of
      highly purified EPA on cardiac and adipose tissue pathophysiology in this animal
      model. MATERIALS AND METHODS: DS/obese rats were administered EPA (300 or 1,000
      mg kg-1 d-1, per os) or vehicle from age 9 to 13 weeks. Homozygous lean (DahlS.Z
      Lepr+/Lepr+, or DS/lean) littermates were studied as controls. RESULTS: Whereas
      EPA had no effect on body weight, food intake or systolic blood pressure in
      DS/obese rats, it attenuated cardiac fibrosis, diastolic dysfunction, oxidative
      stress and inflammation in these animals. In addition, EPA did not affect insulin
      resistance but reduced adipocyte hypertrophy and inflammation in visceral fat of
      DS/obese rats. Moreover, EPA increased circulating levels of adiponectin as well
      as attenuated both the down-regulation of AMP-activated protein kinase
      phosphorylation and the up-regulation of phosphorylation of the p65 subunit of
      nuclear factor-kB in the heart of DS/obese rats. CONCLUSIONS: Treatment of
      DS/obese rats with EPA did not affect hypertension but reduced cardiac fibrosis
      and diastolic dysfunction, with the latter effects being accompanied by AMP
      activated protein kinase activation and inactivation of nuclear factor-kB
      signalling in the heart, possibly as a result of an increase in adiponectin
      secretion. EPA may be suitable for the treatment of cardiac injury associated
      with metabolic syndrome.

PMID- 27708848
TI  - Metabolomics-identified metabolites associated with body mass index and
      prospective weight gain among Mexican American women.
AB  - OBJECTIVE: Obesity is a metabolic disease. However, the underlying molecular
      mechanisms linking metabolic profiles and weight gain are largely unknown.
      METHODS: Here, we used semi-targeted metabolomics to assay 156 metabolites
      selected from 25 key metabolic pathways in plasma samples from 300 non-smoking
      healthy women identified from Mano-A-Mano, the Mexican American Cohort study. The
      study subjects were randomly divided into two cohorts: training (N = 200) and
      testing (N = 100) cohorts. Linear regression and Cox proportional hazard
      regression were used to assess the effect of body mass index (BMI) at baseline on
      metabolite levels and the effects of metabolites on significant weight gain
      during a 5-year follow-up. RESULTS: At baseline, we observed 7 metabolites
      significantly associated with BMI in both training and testing cohorts. They were
      Methyl succinate, Asparagine, Urate, Kynurenic acid, Glycine, Glutamic acid, and
      Serine. In further analysis, we identified 6 metabolites whose levels at baseline
      predicted significant weight gain during 5-year follow-up in both cohorts. They
      were Acetylcholine, Leucine, Hippuric acid, Acetylglycine, Urate, and Xanthine.
      CONCLUSIONS: The findings establish the baseline metabolic profiles for BMI, and
      suggest new metabolic targets for researchers attempting to understand the
      molecular mechanisms of weight gain and obesity.

PMID- 27708851
TI  - Heart failure, chronic obstructive pulmonary disease, and asthma: numbers, facts,
      and challenges.
AB  - Heart failure (HF), chronic obstructive pulmonary disease (COPD), and asthma are
      considered as major health problems. They affect 1-3%, 4-10%, and 8-19% of
      population, respectively, and frequently coexist. Pulmonary function testing and
      echocardiography are needed for reliable diagnosis, but in clinical practice,
      diagnosis often is based on history and disease self-reporting. Concomitant HF
      can be diagnosed in about 20% of patients with COPD, and at least 50% had
      systolic dysfunction. In patients with HF, prevalence of COPD is up to 35%, and
      less than 25% of patients have COPD GOLD stage III or IV. COPD is more severe in
      patients with HF with preserved ejection fraction. When HF and COPD coexist,
      hazard of death is increased for 39% but can even exceed the mortality in
      individual disease by threefold. In patients with acute deterioration,
      natriuretic peptides and lung ultrasound, along with other laboratory biomarkers
      and imaging, need to be implemented to differentiate underlying cause and to
      manage patients accordingly. COPD is not contraindication for beta-blockers, and
      if used, the risk of death is reduced by 31%; if indicated, cardio-selective
      agents can be used in asthma. Recent pan-European registry reported that about
      90% of patients with HF receive beta-blockers, whereas dosing remains a large
      unmet need with only 17% being treated with target daily dose. Concurrent HF and
      COPD reduce the prescription of beta blockers threefold, which results in about
      20% of patients actually being treated with beta-blockers. In COPD/asthma, beta
      agonists are strongly associated with new HF (relative risk of 3.41) and HF
      hospitalizations (odds ratio of 1.74).

PMID- 27708852
TI  - Facts and updates about cardiovascular non-coding RNAs in heart failure.
AB  - About 11% of all deaths include heart failure as a contributing cause. The annual
      cost of heart failure amounts to US $34,000,000,000 in the United States alone.
      With the exception of heart transplantation, there is no curative therapy
      available. Only occasionally there are new areas in science that develop into
      completely new research fields. The topic on non-coding RNAs, including
      microRNAs, long non-coding RNAs, and circular RNAs, is such a field. In this
      short review, we will discuss the latest developments about non-coding RNAs in
      cardiovascular disease. MicroRNAs are short regulatory non-coding endogenous RNA
      species that are involved in virtually all cellular processes. Long non-coding
      RNAs also regulate gene and protein levels; however, by much more complicated and
      diverse mechanisms. In general, non-coding RNAs have been shown to be of great
      value as therapeutic targets in adverse cardiac remodelling and also as
      diagnostic and prognostic biomarkers for heart failure. In the future, non-coding
      RNA-based therapeutics are likely to enter the clinical reality offering a new
      treatment approach of heart failure.

PMID- 27708853
TI  - Biological variation of the cardiac index in patients with stable chronic heart
      failure: inert gas rebreathing compared with impedance cardiography.
AB  - AIMS: In chronic heart failure (CHF), changes in cardiac function define the
      course of the disease. The cardiac index (CI) is the most adequate indicator of
      cardiac function. Interpretation of serial CI measurements, however, requires
      knowledge of the biological variation of CI. Because measurements of CI can be
      confounded by the clinical situation or the method applied, biological variation
      might be subject to the same confounders. METHODS AND RESULTS: We prospectively
      included 50 CHF patients who met rigid criteria for clinical stability. CI was
      measured by both inert gas rebreathing (IGR) and impedance cardiography (ICG) in
      weekly intervals over 3 weeks-each measurement performed at rest
      (IGRrest/ICGrest) and during low-exercise 10 Watt pedalling (IGR10W/ICG10W).
      Intra-class correlation coefficients (ICCs), reference change values, and minimal
      important differences of CI were determined for IGRrest, ICGrest, IGR10W, and
      ICG10W. Impedance cardiography and IGR showed moderate agreement at rest (20% (6
      36)) and good agreement at 10 Watt (-4% (-23-16)). Depending on time interval,
      measurement modality for CI, and mode, ICC ranged between 0.42 and 0.78, ICC
      values for IGR were lower than those for ICG. Reference change value ranged
      between 3 and 15%, and minimal important difference ranged between 0.2 and 0.5
      L/min/m2. Values for IGR were lower at rest and higher at 10 Watt than those for
      ICG. CONCLUSION: Non-invasive measurements of CI are stable over time.
      Measurement modalities for CI, however, are not interchangeable. Biological
      variation is less pronounced when obtained by ICG. The influence of low-level
      exercise on stability of CI depends on the measurement modality.

PMID- 27708854
TI  - Heterogeneous responses of systolic and diastolic left ventricular function to
      exercise in patients with heart failure and preserved ejection fraction.
AB  - AIMS: This study aimed to evaluate ventricular diastolic properties using three
      dimensional echocardiography and tissue Doppler imaging at rest and during
      exercise in heart failure with preserved ejection fraction (HFpEF) patients with
      borderline evidence of diastolic dysfunction at rest. METHODS AND RESULTS:
      Results obtained from 52 HFpEF patients (left ventricular ejection fraction >=
      50%) identified on the basis of heart failure symptoms and E/E' values between 8
      and 15 were compared with those obtained in 26 control patients with no evidence
      of cardiovascular disease. Mitral flow patterns, tissue Doppler imaging, and
      volume analysis obtained by three-dimensional echocardiography were performed at
      rest and during bicycle exercise. Diastolic compliance was indexed by the E/E'
      ratio and left ventricular end-diastolic volume [(E/E')/EDV]. There were no
      significant differences in end-diastolic volume (EDV), stroke volume (SV), or
      ejection fraction at rest between groups. In 27 of the 52 patients, E/E'
      increased during exercise (11.2 +/- 3.7 to 16.8 +/- 10.5), driven by a failure to
      augment early diastole (E'). This correlated with a fall in SV and was associated
      with an increase in the diastolic index (E/E')/EDV as a measure for LV stiffness
      (0.122 +/- 0.038 to 0.217 +/- 0.14/mL), indicating that impaired diastolic
      reserve (designated PEF-IDR) contributed to exercise intolerance. Of the 52
      patients, 25 showed no changes in E/E' during exercise associated with a
      significant rise in SV and cardiac output, still inappropriate compared with
      controls. Despite disturbed early diastole (E'), a blunted increase in estimated
      systolic LV elastance indicated that impaired systolic reserve and chronotropic
      incompetence rather than primarily diastolic disturbances contributed to exercise
      intolerance in this group (designated PEF). CONCLUSION: Three-dimensional stress
      echocardiography may allow non-invasive analysis of changes in cardiac output
      that can differentiate HFpEF patients with an inappropriate increase or a fall in
      SV during exercise. Impaired systolic or diastolic reserve can contribute to
      these haemodynamic abnormalities, which may arise from different underlying
      pathophysiologic mechanisms.

PMID- 27708855
TI  - Levosimendan improves exercise performance in patients with advanced chronic
      heart failure.
AB  - AIMS: Cardiopulmonary exercise test (CPET) provides parameters such as peak VO2
      and ventilation/CO2 production (VE/VCO2) slope, which are strong prognostic
      predictors in patients with stable advanced chronic heart failure (ADHF). The
      study aim was to evaluate the effects of the inodilator levosimendan on CPET in
      patients with ADHF under stable clinical conditions. METHODS AND RESULTS: We
      enrolled patients with ADHF (peak VO2 < 12 mL/min/kg) in a double-blind, placebo
      controlled protocol. Patients were randomly assigned to i.v. infusion of placebo
      (500 mL 5% glucose; n = 19) or levosimendan (in 500 mL 5% glucose; n = 23).
      Before and 24 h after the end of the infusion, patients underwent determination
      of New York Heart Association class, B-type natriuretic peptide (BNP),
      haemoglobin, serum creatinine, and blood urea nitrogen levels, as well as CPET,
      standard spirometry, and alveolar capillary gas diffusion. BNP showed no change
      with placebo (1042 +/- 811 to 1043 +/- 867 pg/mL), but it was decreased with
      levosimendan (1163 +/- 897 to 509 +/- 543 pg/mL, P < 0.001). No changes were
      observed for haemoglobin, creatinine, and blood urea nitrogen in either group.
      With levosimendan, a minor improvement was observed in spirometry measurements,
      but not in alveolar capillary gas diffusion. Peak VO2 showed a small, non
      significant increase with placebo (9.5 +/- 1.7 to 10.0 +/- 2.1 mL/kg/min, P =
      0.12), and a greater increase with levosimendan (9.8 +/- 1.7 to 11.0 +/- 1.9
      mL/kg/min, P < 0.005). The VE/VCO2 slope showed no change (44.0 +/- 11 vs. 43.4
      +/- 10.3, P = 0.44), and a decrease (41.9 +/- 10 vs. 36.6 +/- 6.4, P < 0.001) in
      the placebo and in the levosimendan group, respectively. CONCLUSION: Levosimendan
      treatment significantly improves peak VO2 and reduces VE/VCO2 slope and BNP in
      patients with ADHF.

PMID- 27708856
TI  - Validation of the FEW16 questionnaire for the assessment of physical well-being
      in patients with heart failure with reduced ejection fraction: results from the
      CIBIS-ELD study.
AB  - AIMS: Patients with heart failure (HF) commonly suffer from severe impairment of
      quality of life (QoL). One main goal of HF treatment is improvement of QoL.
      Physical well-being is an essential component of QoL. To enable assessment of
      physical well-being in HF patients, we validated the FEW16 questionnaire in a
      prospective study with patients from the Cardiac Insufficiency Bisoprolol Study
      in ELDerly. METHODS AND RESULTS: In 127 HF patients (age 73 +/- 5.5 years, 72%
      male, 60% New York Heart Association class II, left ventricular ejection fraction
      37 +/- 8.5%), we measured physical well-being (FEW16), QoL [36-Item Short-Form
      Health Survey (SF36)], and depressive symptoms [PRIME MD Patient Health
      Questionnaire German short version for depression (PHQ-D)] at baseline and two
      follow-up visits, and correlated FEW16 scores with QoL data and clinical
      parameters. FEW16 mean scores are 3.04 +/- 1.04 at baseline, 3.19 +/- 0.94 after
      3 months, and 2.77 +/- 0.94 after 2-4 years. We assessed data quality, scale
      assumptions, and construct validity and reliability. Cronbach's alpha for
      subscales resilience: 0.84; ability to enjoy: 0.80; vitality: 0.88; inner peace:
      0.87; total score: 0.95. Intraclass correlation coefficient (ICC) is 0.87 (95% CI
      0.84-0.89, ICC (1.4). Pearson's correlations of FEW16 with SF36 and PHQ-D were
      significant. Six minutes walking distance and heart rate correlated significantly
      with the FEW16 total score. CONCLUSIONS: The FEW16 showed good reliability,
      internal consistency, and intraclass correlation. FEW16 scores correlated well
      with psychological and physical well-being (SF36) and clinical markers of
      exercise tolerance (6 min walk test and heart rate). Our results indicate a
      strong correlation of self-reported physical well-being with psychological
      factors. FEW16 values at baseline predicted the development of several aspects of
      QoL during beta-blocker up-titration.

PMID- 27708857
TI  - Risk stratification of patients with chronic heart failure using cardiac iodine
      123 metaiodobenzylguanidine imaging: incremental prognostic value over right
      ventricular ejection fraction.
AB  - AIMS: Right ventricular (RV) systolic dysfunction has been shown to be an
      independent predictor of clinical outcome in patients with chronic heart failure
      (CHF), and cardiac metaiodobenzylguanidine (MIBG) imaging also provides
      prognostic information. We aimed to evaluate the long-term predictive value of
      combining RV systolic dysfunction and abnormal findings of cardiac MIBG imaging
      on outcome in CHF patients. METHODS AND RESULTS: We enrolled 63 CHF outpatients
      with left ventricular ejection fraction (EF) <40% in a prospective cohort study.
      At entry, RVEF was measured by radionuclide angiography. Furthermore, cardiac
      MIBG imaging was performed, and the cardiac MIBG washout rate (WR) was
      calculated. Reduced RVEF was defined as <=37%, and abnormal WR was defined as
      >27%. The study endpoint was unplanned hospitalization for worsening heart
      failure (WHF) and cardiac death. During a follow-up period of 8.9 +/- 4.3 years,
      19 of 63 patients had unplanned hospitalization for WHF, and 19 of 63 patients
      had cardiac death. In multivariate analysis, both WR and RVEF were independent
      predictors of unplanned WHF hospitalization, while WR was also an independent
      predictor of cardiac death. A risk-stratification model based on independent
      predictors of unplanned WHF hospitalization separated the patients into those
      with low (absence of the predictors), intermediate (one of the predictors), and
      high (two or more of the predictors) risk of unplanned WHF hospitalization (P <
      0.0001) or cardiac death (P = 0.0113). CONCLUSIONS: Cardiac MIBG imaging provides
      incremental value when it is used along with RV systolic dysfunction to predict
      clinical outcome in patients with CHF.

PMID- 27708858
TI  - Mid wall fibrosis on CMR with late gadolinium enhancement may predict prognosis
      for LVAD and transplantation risk in patients with newly diagnosed dilated
      cardiomyopathy-preliminary observations from a high-volume transplant centre.
AB  - BACKGROUND: Patients with newly diagnosed dilated cardiomyopathy (DCM) and
      advanced heart failure have a very high morbidity and mortality with an
      unpredictable clinical course. We investigated the role of cardiovascular
      magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) in this
      cohort of high-risk patients. We hypothesized that LGE has high prognostic value
      in primary DCM patients referred for possible transplantation/left ventricular
      assist device (LVAD) consideration. METHODS: Over 49 consecutive months, 61
      consecutives DCM patients were referred for standard CMR(1.5T, GE) to interrogate
      the LV pattern, distribution, and extent of LGE (MultiHance, Princeton, NJ).
      Inclusion criteria for a primary non-ischaemic DCM and EF <45% were met in 31
      patients. DCM patients were categorized into: (i) presence of midwall LV stripe
      (+Stripe) and (ii) absence of midwall stripe (-Stripe) groups. Primary outcome
      was defined by the composite of death, need for LV assist device (LVAD), and
      urgent orthotopic cardiac transplantation (Tx) during a 12-month follow-up
      period. Kaplan-Meier survival analysis was conducted grouping patients by +Stripe
      and -Stripe. RESULTS: There were no differences between groups for demographics,
      blood pressure, labs, baseline LVEF, NYHA class, or invasive haemodynamics. There
      were 18 patients (58%) with +Stripe. Nine events occurred: seven patients
      required urgent Tx and/or LVAD implantation and two patients died. The +Stripe
      categorization strongly predicted the need for LVAD, urgent Tx surgery, and death
      (log-rank = 9, P = 0.002). All the events occurred in the +Stripe patients with
      no MACE experienced in the -Stripe group. The -Stripe group experienced marked
      signs of improvement in LVEF (P = 0.01) at follow-up. LVEDD was predictive of
      need for LVAD/Tx and death by univariate analysis. Otherwise, no common clinical
      metric such as LVEF, LVEDV, RVEF, RVEDV, or any invasive haemodynamic parameter
      predicted MACE. CONCLUSIONS: The presence of +Stripe on CMR is strongly
      predictive of LVAD, transplant need, and death during a 12-month follow-up period
      in DCM patients in this proof of concept study. All -Stripe patients survived
      without experiencing any events. Incorporating CMR imaging into routine clinical
      practice may have prognostic value in DCM patients; indicating conservative
      management in low-risk patients while expectantly managing high-risk patients.

PMID- 27708859
TI  - Polypyrrole-incorporated conductive hyaluronic acid hydrogels.
AB  - BACKGROUND: Hydrogels that possess hydrophilic and soft characteristics have been
      widely used in various biomedical applications, such as tissue engineering
      scaffolds and drug delivery. Conventional hydrogels are not electrically
      conductive and thus their electrical communication with biological systems is
      limited. METHOD: To create electrically conductive hydrogels, we fabricated
      composite hydrogels of hyaluronic acid and polypyrrole. In particular, we
      synthesized and used pyrrole-hyaluronic acid-conjugates and further chemically
      polymerized polypyrrole with the conjugates for the production of conductive
      hydrogels that can display suitable mechanical and structural properties.
      RESULTS: Various characterization methods, using a rheometer, a scanning electron
      microscope, and an electrochemical analyzer, revealed that the PPy/HA hydrogels
      were soft and conductive with ~ 3 kPa Young's modulus and ~ 7.3 mS/cm
      conductivity. Our preliminary in vitro culture studies showed that fibroblasts
      were well attached and grew on the conductive hydrogels. CONCLUSION: These new
      conductive hydrogels will be greatly beneficial in fields of biomaterials in
      which electrical properties are important such as tissue engineering scaffolds
      and prosthetic devices.

PMID- 27708860
TI  - Whole-body MRI for full assessment and characterization of diffuse inflammatory
      myopathy.
AB  - BACKGROUND: Conventional magnetic resonance imaging (MRI) is a highly valuable
      tool for full assessment of the extent of bilateral symmetrical diffuse
      inflammatory myopathy, owing to its high sensitivity in the detection of edema
      which correlates with, and sometimes precedes, clinical findings. PURPOSE: To
      evaluate the use of whole-body (WB)-MRI in characterization and full assessment
      of the extent and distribution of diffuse inflammatory myopathy. MATERIAL AND
      METHODS: A prospective study on 15 patients presenting with clinical evidence of
      inflammatory myopathy. It included 4 boys/men and 11 girls/women (age range, 6-44
      years; mean age, 25.5 years). 1.5 T WB-MRI was performed and the distribution and
      extent of disease severity was assessed according to muscle edema on STIR images.
      RESULTS: Four cases of dermatomyositis showed lower limb disease predilection
      with edema in gluteal, thigh, and calf muscles. The same finding was seen in one
      case with recurrent polymyositis and three cases with overlap myositis with
      systemic lupus erythematosus (SLE). Bilateral upper and lower limb myositis was
      demonstrated in three cases of polymyositis and one case of overlap myositis with
      scleroderma. Bilateral edema involving all scanned muscle groups was detected in
      three cases of polymyositis with paraneoplastic syndrome, SLE, and severe active
      dermatomyositis (including the neck muscles). CONCLUSION: WB-MRI is the
      diagnostic modality of choice for cases of inflammatory myopathy. It accurately
      detects the most severely affected muscles candidate for biopsy and provides a
      reliable baseline study for follow-up of disease progression as well as response
      to treatment.

PMID- 27708862
TI  - Dynamics shared by two related proinflammatory conditions, rheumatoid arthritis
      and metabolic syndrome.

PMID- 27708861
TI  - Prevalence of the metabolic syndrome in rheumatoid arthritis.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) experience a markedly
      increased prevalence of cardiovascular disease (CVD), but the causal factors have
      yet to be completely elucidated. Metabolic syndrome (MetS) is a cluster of risk
      factors of CVD and identifies additional cardiovascular risk beyond the sum of
      its individual components. In this study, we investigated the prevalence of MetS
      and its possible relationship with disease-related factors in patients with RA.
      MATERIAL AND METHODS: Fifty-two patients with RA and 30 age- and sex-matched
      healthy controls were studied. Adult Treatment Panel III of the National
      Cholesterol Education Program (NCEP-ATP III) and modified World Health
      Organization (WHO) criteria were used to define MetS. RA disease activity is
      assessed by the disease activity score of 28 joints (DAS28), and the functional
      status of patients was evaluated by Health Assessment Questionnaire (HAQ).
      RESULTS: Although there was no difference between groups regarding the frequency
      of MetS according to NCEP-ATP III criteria (17.3% and 6.5% in RA and control
      groups, respectively (p=0.158)) if modified WHO criteria were used, the
      prevalence of MetS was significantly higher in patients with RA (28.8%) than in
      controls (9.7%) (p=0.04). Central obesity and hypertension were found to be more
      frequent in patients with RA by both NCEP-ATP III and WHO criteria. RA patients
      with MetS had higher systolic and diastolic blood pressure, BMI and frequency of
      smoking than patients without MetS. Disease-related factors were similar in RA
      patients with or without MetS. CONCLUSION: The evaluation of patients with RA for
      MetS, which is a multidimensional risk factor of CVD, may be beneficial.

PMID- 27708863
TI  - Sonographic measurement of Achilles tendon thickness in seronegative
      spondyloarthropathies.
AB  - OBJECTIVE: To define the best cut-off value for identifying Achilles tendon
      thickening using ultrasound (US) in patients with spondyloarthropathies (SpA) and
      to assess its diagnostic utility in comparison with different cut-off values used
      in the literature. MATERIAL AND METHODS: One-hundred and one subjects (55 SpA
      patients and 46 age and body mass index ((BMI)-matched healthy controls (HC))
      were investigated. US was performed using a MyLab70 US system (Esaote Biomedica,
      Genoa, Italy) with a linear probe (6-18 MHz). Three images per Achilles enthesis
      were stored and the antero-posterior thickness of the enthesis was measured at
      the level of the Achilles tendon deeper margin insertion into the calcaneal bone
      on the longitudinal median scan. The best cut-off value for each gender was
      determined by ROC curve analysis and compared to the other cut-off values in the
      literature: 1) 5.29 mm for both genders, and 2) 5.5 mm for females and 6.2 mm for
      males. The number of measurements exceeding the cut-off values as well as
      sensitivity (SE), specificity (SP), positive (PPV) and negative (NPV) predictive
      values were calculated. RESULTS: A significant difference was observed for
      Achilles enthesis thickness between genders (mean+/-SD: 4.6+/-0.7 mm in males vs.
      4.0+/-0.8 mm in females, p<0.00) and between SpA patients and HC (mean+/-SD:
      4.4+/-0.8 mm in SpA patients vs. 4.0+/-0.8 mm in HC, p<0.001). The ROC curve
      analysis revealed the best cut-off value to be 3.7 mm for females and 4.8 mm for
      males (SE: 43-70%, SP: 59-85%, PPV: 66-79%, NPV: 54-63%). Previously reported cut
      off values were found to have high SP (91-98%) but very low SE (2-11%).
      CONCLUSION: Achilles tendon thickness differs between genders; thus, it is
      crucial to refer to normal values that are specific for gender. High cut-off
      values, as previously suggested, showed very low SE in the current study. When
      Achilles enthesis thickening is used for the purpose of screening enthesitis in
      SpA patients, a lower cut-off value has a higher SE with slightly worse SP, PPV
      and NPVs.

PMID- 27708864
TI  - Evaluation of arterial stiffness with plasma GGT levels and pulse wave velocity
      measurement in patients with FMF.
AB  - OBJECTIVE: Pulse wave velocity (PWV) is a non-invasive technique used to evaluate
      the arterial elasticity, which is an early indicator of atherosclerosis. Lately,
      gamma glutamyl transferase (GGT) is considered a determiner of arterial stiffness
      (AS). In this study, we aimed to evaluate the relationship between GGT levels and
      AS with PWV in patients with Familial Mediterranean fever (FMF). MATERIAL AND
      METHODS: The study was conducted with 60 patients with FMF and 40 controls.
      Genetic analysis of the patients were performed. AS was assessed by PWV and,
      after the measurement of PWV, the presence of AS was determined. RESULTS: Mean
      PWV values and AS frequency were significantly higher in patients with FMF
      compared with the control group (p<0.001 and p=0.004, respectively). Mean GGT
      levels of FMF patients were higher than in the control group but the difference
      was not statistically different. In the correlation analysis, PWV and AS were
      positively correlated with FMF (r=0349, p<0.001; r=0.435, p<0.001, respectively).
      FMF duration and FMF were associated with GGT (r=0.300, p=0.02; r=0199, p=0.047,
      respectively). CONCLUSION: Increased PWV values in FMF patients may indicate
      arterial stiffness. These patients may be followed closely with PWV as an early
      indicator of atherosclerosis. Therefore, the cardiovascular risk can be
      determined in the early stages of disease and it may be possible to take
      necessary precautions.

PMID- 27708865
TI  - Serum salusin-alpha levels in systemic lupus erythematosus and systemic
      sclerosis.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc),
      chronic inflammatory diseases, demonstrate an increased incidence of
      cardiovascular manifestations and subclinical atherosclerotic disease. Salusin
      alpha is a novel bioactive peptide that suppresses the formation of macrophage
      foam cells, and its serum level is significantly lower in patients with
      angiographically proven coronary artery disease. The aims of the study were to
      assess serum salusin-alpha level and its potential association with the
      predictors of atherosclerosis in SLE and SSc. MATERIAL AND METHODS: The study
      included 20 SLE and 22 SSc patients and 23 healthy controls (HC). All of the
      participants were female. Tumour necrosis factor-alpha (TNF-alpha), IL-6 and
      salusin-alpha levels, homeostasis model assessment for insulin resistance (HOMA
      IR) index and common carotid intima-media thickness (IMT) were determined.
      RESULTS: Salusin-alpha levels were lower and the IMTs were higher in the SLE and
      SSc groups than in the HC group. The salusin-alpha level was correlated with
      neither the disease activity scores nor cytokine levels and IMT in the SLE and
      SSc groups, although it was correlated with triglyceride level in the SLE group
      (r=-0.564, p=0.012), and with HOMA-IR index in the HC group (r=0.485, p=0.019).
      CONCLUSION: The present preliminary study may support the idea that SSc leads to
      subclinical atherosclerosis, as in SLE. Moreover, it can be concluded that the
      decreased salusin-alpha levels in SLE and SSc may contribute to subclinical
      atherosclerosis. However, further studies with larger sample size are needed to
      demonstrate this contribution in SLE and SSc.

PMID- 27708866
TI  - Autonomic functions in acrocyanosis assessed by heart rate variability.
AB  - OBJECTIVE: To evaluate the autonomic activity of patients with acrocyanosis by
      using heart rate variability indices. MATERIAL AND METHODS: The study group
      consisted of 24 patients with acrocyanosis and the control group contained 22 sex
      and age-matched healthy subjects. All subjects underwent 24-hour Holter
      monitoring. Among the heart rate variability (HRV) parameters, time-domain and
      frequency-domain indices were analysed. RESULTS: The time-domain indices of HRV
      indicating global autonomic functions were found to be increased, and indices
      indicating parasympathetic activity showed a significant decrease in the patient
      group. Power-spectral analysis of HRV revealed that the low frequency and high
      frequency power were higher in the patient group than in controls. However, the
      ratio of Low Frequency/High Frequency was found to be lower in the patient group
      than in controls. CONCLUSION: In acrocyanosis, both sympathetic and
      parasympathetic systems seem to be disrupted. Therefore, we may conclude that
      acrocyanosis may be resulted of systemic autonomic imbalance rather than pure
      sympathetic over-activation. Also, these results suggest that acrocyanosis is not
      a localised disorder; on the contrary, it is associated with various
      abnormalities of the systemic autonomic nervous system.

PMID- 27708868
TI  - Mass-like lesions as a rare form of neuro-Behcet's disease: A case report and
      review of the literature.
AB  - Cerebral mass-like lesion (MLL) is a rare form of Neuro-Behcet's (NB) disease.
      There is currently no detailed knowledge on this issue in the literature. Our aim
      was to describe a Behcet's disease (BD) patient with MLL, followed by a clinical
      analysis in light of the available literature regarding BD patients who suffered
      from an MLL or tumefactive lesion in the brain. We conducted a review of the
      English literature to analyse data on MLL in BD. The Pub-Med, Web of Science,
      Proquest and Ovid databases were searched for articles or abstracts using the
      term "Behcet's disease" combined with one of the following terms: mass-like
      lesion, tumour-like lesion and tumefactive lesion. We compared clinical and
      laboratory features of BD patients with MLL with NB patients. We found 12 cases
      plus our case (6 male, 7 female; mean age: 40 years) with BD who developed MLL
      alongside BD. Five out of 13 BD patients (38%) had a history of BD before the
      onset of neurological symptoms. In 8 patients (62%), BD was diagnosed after the
      onset of neurological involvement. Headache, hemiparesis, dizziness, aphasia,
      nausea and vomiting were the presenting manifestations of NB patients with MLL.
      Genital ulceration, eye involvement, skin lesion and arthritis/arthralgia were
      less commonly reported in NB patients with MLL compared to NB patients without
      MLL. NB disease should be considered in the differential diagnosis of cerebral
      MLL even when other cardinal manifestations of BD are absent. Mucocutaneous
      manifestations, eye and joint involvement may be seen less often in these
      patients.

PMID- 27708869
TI  - Coexistence of systemic lupus erythematosus and ankylosing spondylitis: another
      case report and review of the literature.
AB  - The coexistence of systemic lupus erythematosus (SLE) and ankylosing spondylitis
      (AS) is very rare, and, to the best of our knowledge, there are only 8 reported
      cases in the English literature. Here, we present another case with the
      coexistence of these two diseases, and review the clinical and laboratory
      features of the previously reported cases. A 55 year-old female patient, with a
      diagnosis of SLE with locomotor, skin, renal and hematopoietic system
      involvement, which had been confirmed by relevant autoantibody positivity, and
      hypocomplementemia and biopsy-proven membranous lupus nephritis, was referred to
      our clinic suffered from typical inflammatory low-back pain after eight years of
      follow-up. Sacroiliac magnetic resonance imaging (MRI) confirmed the presence of
      bilateral active sacroiliitis with bone marrow oedema. HLA-B27 was positive and
      bilateral calcaneal spurs were also detected by conventional radiography.
      Therefore, the additional diagnosis of AS was made, eight years after the
      diagnosis of SLE. Inflammatory low-back pain typically responded to treatment
      with non-steroidal anti-inflammatory drugs. Including the present case, most of
      the reported cases of the coexistence of SLE and AS are female, and SLE generally
      precedes the occurrence of AS. The present case is also notable as the patient
      had both MRI confirmation of bilateral active sacroiliitis and HLA-B27
      positivity. The coexistence of these two diseases with different genetic
      backgrounds in the same patient is much lower than expected based upon their
      prevalence in the general population. Although it has been suggested that the
      very rare combination of the susceptibility genes of each disease may explain the
      rarity of coexistence, epidemiological data concerning the genetic risks for the
      coexistence of SLE and AS are not available.

PMID- 27708871
TI  - Herpetic whitlow during immunosuppressive therapy for Wegener's Granulomatosis.
AB  - Skin involvement may occur in patients with Wegener's granulomatosis
      (polyangiitis with granulomatosis; WG) and is more frequent in the generalised
      form. However, when a patient with vasculitis develops digital ulceration, in
      addition to disease activation, other pathologies should be considered. One of
      them may be the herpetic whitlow mimicking paronychia. Here, we present a patient
      who developed herpetic whitlow during the course of immunosuppressive therapy due
      to WG. Just before the third course of cyclophosphamide therapy, she was re
      admitted to the outpatient clinic with the above-mentioned ulcerated lesions. On
      physical examination, there was erythema and a painful, crusted ulceration in the
      distal phalanx of the right index finger involving the proximal nail fold.
      Similar lesions were also present in her lower lip. Due to the absence of
      clinical and laboratory findings suggesting the activation of WG and the Tzanck
      smear result, which is compatible with herpes virus infection, we do not believe
      that WG was responsible for our patient's complaints. All of the patient's
      lesions completely disappeared following the interruption of immunosuppressive
      therapy.

PMID- 27708872
TI  - Endoscopic appearance of Henoch-Schonlein purpura.

PMID- 27708870
TI  - Thrombocytopenia caused by albendazole in a patient with Sjogren's syndrome: A
      case report.
AB  - Sjogren's syndrome (SS) is an autoimmune disease characterised by a chronic
      inflammatory response mainly localised to the lachrymal and salivary glands.
      Haematological abnormalities are common, although they rarely have clinical
      significance. Here, we report a patient with SS and thrombocytopenia caused by
      albendazole. Haematological abnormalities such as thrombocytopenia are seen in
      approximately 5-15% of SS patients; however, this disease is usually asymptomatic
      and can often be recovered to normal levels with corticosteroids. If it is not,
      we should keep in mind other reasons for the thrombocytopenia, such as drug use.

PMID- 27708867
TI  - Familial Mediterranean fever: An updated review.
AB  - Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder
      characterised by acute attacks of fever and serosal inflammation. FMF primarily
      affects Jewish, Armenian, Turkish, and Arab populations. The disease is
      accompanied by a marked decrease in quality of life due to the effects of attacks
      and subclinical inflammation in the attack-free periods. Untreated or
      inadequately treated patients run the risk of amyloidosis, which is an important
      cause of morbidity and mortality. In this review, the current information
      available on FMF is summarised.

PMID- 27708873
TI  - The clinical utility of anti-CCP antibodies in rheumatoid arthritis and psoriatic
      arthritis.

PMID- 27708874
TI  - Prevalence of hepatitis B and C infections in rheumatoid arthritis and ankylosing
      spondylitis: A multicenter countrywide study.
AB  - OBJECTIVE: Immunosuppressive therapies, especially tumor necrosis factor-alpha
      inhibitors, are frequently used in treatment of rheumatoid arthritis (RA) and
      ankylosing spondylitis (AS). These therapies can induce viral reactivation in
      concurrent hepatitis B virus (HBV)- or hepatitis C virus (HCV)-positive patients.
      On the other hand, the prevalence of HBV and HCV infections is not exactly known
      in RA and AS patients. The aim of this study was to investigate the prevalence of
      HBV and HCV infections in RA and AS patients. MATERIAL AND METHODS: A group of
      1517 RA and 886 AS consecutive patients followed by six different rheumatology
      outpatient clinics of Turkey were recruited in this study. The prevalence of HBV
      surface antigen (HBsAg) and HCV antibody (anti-HCV) were retrospectively
      investigated. RESULTS: The mean age was 49.0+/-13.2 years in RA and 37.3+/-10.5
      years in AS patients. HBsAg prevalence was 35 (2.3%) in RA and 27 (3%) in AS
      patients. Anti-HCV prevalence was 17 (1.1%) and 10 (1.1%), respectively. In the
      RA group, both HBsAg and anti-HCV positive patients were older than negative ones
      (p<0.05), and the highest prevalence was found in those 60-69 years (p<0.05).
      CONCLUSION: In previous national data, the prevalence of HBsAg has been reported
      as 3.99% and shown to increase with age. In this study we have found a lower HBV
      infection prevalence in both RA and AS patients according to Turkish national
      data. This result may explain by being younger age of our patients. In another
      conclusion, lower prevalence could be related to, joint complaints may less
      consulted to Rheumatologist in HBV positive.

PMID- 27708875
TI  - Mental health status can reflect disease activity in rheumatoid arthritis.
AB  - OBJECTIVE: A significant number of patients with rheumatoid arthritis (RA) link
      the start of illness with psychological trauma or severe stress. Impaired mental
      health (IMH), defined as depression and anxiety with psychoneuroimmunological
      factors, can play a significant role in RA. The main objective of this research
      was to investigate the mutual correlation of IMH and RA activity, estimated by
      the laboratory and clinical parameters in RA patients. MATERIAL AND METHODS: An
      open clinical prospective study that lasted for 6 months was designed. There were
      72 patients included, 58 women and 14 men, aged 34 to 80 years and screened for
      mental health status. The study population was randomized following the Brief
      Symptoms Inventory (BSI) scale, comprised of 53 questions with a range from 0 (no
      symptoms) to 4 (severe). This mental test was done only once during the study.
      Following the results from the BSI scale, RA patients were divided into mentally
      stable and mentally unstable patients to investigate the influence of RA activity
      on mental health. The following laboratory and clinical parameters were analyzed:
      sex, age, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C
      reactive protein (CRP), anti-cyclic citrullinated peptide (anti-CCP) antibody,
      and disease activity score (DAS28). All RA patients did not express extra
      articular manifestations or Sjogren's syndrome. The chi-square test, ANOVA,
      Pearson's coefficient, and IBM Statistics - SPSS v19 were used. RESULTS: From a
      total of 72 RA patients, there were 44 mentally stable and 28 mentally unstable
      patients. All patients had either moderate or severe active disease. The only
      significant correlation of IMH and activity of RA was found in CRP and DAS28, but
      no significance was observed in ESR, RF, and anti-CCP. The DAS28 showed high
      disease activity with an average of 5.3 and CRP of 20.9 mg/L in patients with
      unstable mental health compared to stable mental health patients, where RA was
      associated with a moderate DAS average value of 4.35 and CRP of 14.1 mg/L.
      Depression and anxiety were found in all 28 (39%) RA patients. CONCLUSION:
      Mentally unstable RA patients correlate more with severe disease activity, while
      mentally stable patients express moderate disease activity.

PMID- 27708876
TI  - Heart rate variability in familial Mediterranean fever patients.
AB  - OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive
      autoimmune disease, presenting with the attacks of fever and inflammation of
      serous membranes. One of the leading causes of death in autoimmune rheumatologic
      diseases is cardiovascular events. The purpose of this study is to evaluate the
      effects of FMF on the autonomic nerve and cardiovascular systems by measuring the
      indices of heart rate variability (HRV). MATERIAL AND METHODS: Thirty FMF
      patients and the same number of healthy volunteers were enrolled to the study.
      Standard deviation of all R-R intervals (SDNN), the square root of the sum of the
      square of the differences between successive R-R intervals (RMSSD), standard
      deviation of 5-minute mean values of R-R interval (SDANN), low frequency (LF),
      and high frequency (HF) were measured. RESULTS: Time domain indices (SDNN, SDANN,
      and RMSSD) were: 124.67+/-40.79, 129.87+/-36.43 (p=0.605); 11.43+/-38.41, 11.23+/
      38.98 (p=0.984); and 33.43+/-17.39, 38.17+/-12.8 (p=0.235) for FMF patients and
      controls, respectively, and similar in both groups. Frequency domain indices (HF,
      LF, and LF/HF) were: 290.41+/-290.25, 322.20+/-222.54 (p=0.639); 596.16+/-334.07,
      805.80+/-471.00 (p=0.051); and 3.57+/-2.57, 3.05+/-1.40 (p=0.338) for FMF
      patients and controls, respectively, and similar in both groups. CONCLUSION: The
      HRV parameters were similar in both groups. However, studies including larger
      populations and using different methods are required to clarify if autonomic
      dysfunction exists in patients with FMF.

PMID- 27708877
TI  - Does isoniazid chemoprophylaxis increase the frequency of hepatotoxicity in
      patients receiving anti-TNF-alpha agent with a disease-modifying antirheumatic
      drug?
AB  - OBJECTIVE: The aim of this study is to determine the incidence of isoniazid (INH)
      related hepatotoxicity in patients with rheumatologic diseases receiving tumor
      necrosis factor-alpha (TNF-alpha) antagonists along with a disease-modifying
      antirheumatic drug (DMARD). MATERIAL AND METHODS: We have retrospectively
      evaluated 87 patients receiving anti-TNFalpha agents who were followed up between
      June 2005 and February 2010 at our rheumatology department. Sixty-one of 87
      patients have received INH prophylaxis for 9 months for latent tuberculosis
      infection. RESULTS: A total of 61 (70.1%) of 87 patients used INH prophylaxis
      (Group I), while the remaining 26 (29.9%) (Group II) had not; 53 patients had
      used any DMARD in Group I, while 21 patients had used in Group II. No significant
      differences were found among Group I and II with respect to clinical features.
      When two groups were compared, in Group I, elevations of liver enzymes were
      detected in five patients (8.1%) who had normal baseline values. Among these
      patients, hepatotoxicity developed in two patients. Hepatotoxicity developed one
      patient in Group II (p=0.85). CONCLUSION: INH chemoprophylaxis was well tolerated
      in patients using anti-TNF-alpha agent and a DMARD. It seems not to be a strong
      risk factor for hepatotoxicity. However, comorbidities and other drugs used may
      be additional factors in the elevation of transaminases.

PMID- 27708878
TI  - The Frequency of anti-CCP antibodies in patients with rheumatoid arthritis and
      psoriatic arthritis and their relationship with clinical features and parameters
      of angiogenesis: A comparative study.
AB  - OBJECTIVE: Macrophage migration inhibitory factor (MIF) and vascular endothelial
      growth factor (VEGF), as crucial parameters of angiogenesis and inflammation,
      were evaluated to identify the role of cyclic citrullinated peptide antibodies
      (anti-CCP) during angiogenesis in rheumatoid arthritis (RA) and psoriatic
      arthritis (PsA). MATERIAL AND METHODS: A total of 145 patients with RA, 44
      patients with PsA, and 73 healthy subjects were included in this study. The
      clinical features, total blood counts, and acute phase parameters of RA and PsA
      patients were recorded. Anti-CCP antibody, VEGF, and MIF levels were determined
      with enzyme-linked immunosorbent assay (ELISA). RESULTS: Anti-CCP positivity was
      significantly higher in the RA group (69%) than in both PsA (20.6%) and controls
      (8.2%) (p values<0.001). There was no difference between anti-CCP-positive and 
      negative RA patients regarding the extra-articular manifestations (p>0.05). VEGF
      and MIF levels were similar in anti-CCP-positive and -negative RA patients (all p
      values>0.05). The specificity of anti-CCP antibodies for RA was found to be
      87.2%. No relationship was found between anti-CCP antibody positivity and
      clinical features, disease activity, functional disability as assessed by health
      assessment questionnaire scores, and extra-articular manifestations. There was no
      relationship between parameters of angiogenesis and anti-CCP antibody positivity.
      Both RF and anti-CCP antibodies were observed to be positive in most patients
      with RA. CONCLUSION: Either RF or anti-CCP antibody was positive in a
      considerable proportion of our RA patients. Therefore, anti-CCP antibodies are
      important in the diagnosis of RF-negative patients who present with clinical
      findings of RA.

PMID- 27708880
TI  - A rare location of sacral tuberculosis: A report of three cases.
AB  - Tuberculosis remains one of the most common infectious diseases in the world.
      Vertebral tuberculosis is the commonest form of bone and joint tuberculosis;
      however, isolated sacral tuberculosis is rare. This atypical presentation may
      lead to a delay in diagnosis and treatment. We report three cases of sacral
      tuberculosis diagnosed in young women, aged 30, 23, and 35 years old,
      respectively. Lombosciatic pain was the main symptom in all cases. All patients
      had a biological assessment, plain radiographs, and CT scan. However, magnetic
      resonance imaging was done in only two cases. All patients underwent surgical
      sacral biopsy, and the diagnosis of tuberculosis was confirmed by histology in
      all cases. The evolution was satisfactory with the adjunction of antituberculous
      chemotherapy in all cases. Spinal tuberculosis should be the first and foremost
      differential diagnosis in the presence of atypical clinical and radiological
      features of a sacral lesion, particularly in developing countries. Early
      diagnosis and treatment could prevent or minimize the neurological morbidity in
      such cases.

PMID- 27708881
TI  - Nailfold capillaroscopy in Buerger's disease: A useful tool?
AB  - Thromboangiitis obliterans (TAO, or Buerger's disease) is a rare inflammatory
      vasculitis that commonly involves small and medium-sized arteries of the
      extremities of tobacco smokers between the ages of 25 and 50 years. Although the
      diagnosis is based on the clinical picture and angiographic findings, we studied
      the microvascular involvement by nailfold capillaroscopy. We evaluated by
      nailfold capillaroscopy 2 patients with Buerger's disease, at baseline and after
      6 months of tobacco discontinuation and therapy with prostanoids. Both patients
      presented similar capillaroscopic abnormalities, resembling a scleroderma-like
      pattern. The microvascular rearrangement was significantly reduced after 6 months
      of evaluation. The capillaroscopic abnormalities shown in the two patients could
      be related to thromboangiitis obliterans, and nailfold capillaroscopy could be a
      useful tool to evaluate disease progression and the response to treatment.

PMID- 27708879
TI  - An old disease with new insights: Update on diagnosis and treatment of gout.
AB  - Gout is an acute and chronic inflammatory disorder associated with high morbidity
      and impaired quality of life. There has been a substantial increase in the
      prevalence and incidence of gout in recent years. Novel diagnostic and
      therapeutic options have provided new insights into the pathogenesis and
      management of hyperuricemia and gout in the last decade. This clinical review
      aims to summarize the diagnostic process and management of acute and chronic
      gout.

PMID- 27708883
TI  - Does epithelial-mesenchymal transition happen in rheumatoid joints?

PMID- 27708882
TI  - Sjogren's syndrome complicated with retroperitoneal Non-Hodgkin's lymphoma: A
      case of an elderly woman during methotrexate treatment, treated with R-CHOP.

PMID- 27708884
TI  - Dramatic change in disease activity visualized by PET in a patient with
      sarcoidosis.

PMID- 27708885
TI  - Is there any relationship between season/weather and oral ulcer in Behcet's
      disease?
AB  - OBJECTIVE: Some rheumatic diseases are being influenced by weather conditions. We
      examined the relationship between oral ulcers and weather/season in Behcet's
      disease (BD) patients and evaluated the oral ulcers' characteristics by the
      patients' perspectives. MATERIAL AND METHODS: Patients with BD were evaluated
      using a self-questionnaire, including patients' clinical and demographical
      characteristics and detailed characteristics of oral ulcers and the association
      with season. RESULTS: The most common site of oral ulcers was the tongue (89%).
      Of 90 patients, there were predisposing factors in oral ulcers. Among patients
      with BD, 30 believed that seasonal variation aggravated their oral ulcers,
      especially in winter and autumn. CONCLUSION: The exacerbation of oral ulcers in
      patients with BD may be related to the seasons. The weather changes in our study
      are based on the patients' impression; these should be confirmed by objective
      findings and clinical assessment in further studies.

PMID- 27708886
TI  - The correlation between ferritin level and acute phase parameters in rheumatoid
      arthritis and systemic lupus erythematosus.
AB  - OBJECTIVE: In this study, we evaluated the relationship between ferritin levels
      and disease activation in rheumatoid arthritis (RA) patients. MATERIAL AND
      METHODS: We included 44 patients with RA, 20 patients with systemic lupus
      erythematosus (SLE), 25 patients with infection, 22 patients with malignancy, and
      20 healthy control subjects. Erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP), whole blood count, and serum iron parameters were determined in
      all cases. The joint findings in RA patients were recorded, and disease activity
      score (DAS) was calculated. In SLE patients, antinuclear antibody (ANA) and anti
      dsDNA titers and C3 and C4 complement levels were determined. SLE disease
      activity index (SLEDAI) score was calculated. RESULTS: Serum ferritin levels in
      the RA, SLE, and control groups were lower than those in the infection and
      malignancy groups (p<0.05). The ferritin levels in the RA group did not differ
      significantly from the SLE and control groups. In RA patients, serum ferritin
      level had a positive correlation with ESR, CRP, RF, platelet count, and DAS score
      and had a negative correlation with hematocrit (all p values <0.05). In SLE
      patients, on the other hand, serum ferritin had a positive correlation with ANA,
      anti-dsDNA, and SLEDAI (all p values <0.05). According to DAS, ferritin level in
      inactive RA patients was lower than that in active RA patients. When transferrin
      saturation was considered, iron deficiency anemia was a quite frequent finding in
      both active and inactive RA patients. CONCLUSION: Interestingly, we observed that
      ferritin level in RA patients was similar to the control group; however, it was a
      good parameter of disease activation. This is because a reduction in storage iron
      and resultant iron deficiency anemia are very common in RA patients.

PMID- 27708887
TI  - Inflammatory myopathies: One-center experience.
AB  - OBJECTIVE: Our aim was to report our experience with inflammatory myositis.
      MATERIAL AND METHODS: In total, 60 patients were evaluated retrospectively, and
      43 of them (71.7%) were female. The median age was 45 (17-81). Of all patients,
      33 (55%) were diagnosed as polymyositis, 22 (36.6%) as dermatomyositis
      (classical, amyopathic, and malignancy-associated), and 5 (8.33%) as
      undifferentiated myositis. The 3 patients with malignancy-associated
      dermatomyositis had lung cancer, nasopharyngeal carcinoma, and endometrial
      cancer. Two patients with polymyositis had a history of low-grade gastric mixed
      tumor and thymoma but were diagnosed 7 and 12 years ago, and no recurrences have
      been reported during the routine controls. RESULTS: All patients, other than two
      with malignancy-associated dermatomyositis, were treated via immunosuppressive
      agent, and the third patient with lung cancer was diagnosed later and gave up
      immunosuppressive therapy. Thirty-nine (65%) of the patients were treated via
      oral low-dose steroid, and 19 (31.7%) were treated via intravenous high-dose
      pulse steroid therapy. All patients were treated with steroid, which was tapered
      by time, and 23 (38.3%) were treated with azathioprine, 6 (10%) were treated with
      cyclophosphamide, 3 (5%) were treated with methotrexate, and 6 (10%) were treated
      with isolated steroid therapy at the time of diagnosis. The median follow-up
      period was 37 (2-135) months. Six patients (10%) have died-3 due to myocardial
      infarction, 1 due to septic shock, 1 due to malignancy, and 1 with an unknown
      reason. The 5-year survival rate was 76.9%, and the 10-year survival rate was
      40%. CONCLUSION: Other than the high ratio of PM in our series, all other results
      were compatible with the literature. We faced few resistant diseases; therefore,
      biologic agents were used rarely.

PMID- 27708888
TI  - Neutrophil lymphocyte ratio can be a valuable marker in defining disease activity
      in patients who have started anti-tumor necrosis factor (TNF) drugs for
      ankylosing spondylitis.
AB  - OBJECTIVE: Neutrophil lymphocyte ratio (NLR) has emerged as a valuable and
      reliable method for follow-up of systemic inflammatory disease. We herein aimed
      to evaluate the role of NLR in the clinical follow-up of inflammation and also to
      compare its relationship with other measures, such as erythrocyte sedimentation
      rate (ESR), C-reactive protein (CRP), and Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI). MATERIAL AND METHODS: A total of 35 active ankylosing
      spondylitis (AS) and 38 healthy volunteers were included in the study. The
      patient group was enrolled for treatment with one anti-tumor necrosis factor
      (TNF) drug. Total blood count, ESR, CRP, and BASDAI score were obtained before
      and 3 months following the treatment. NLR was found with a mathematical
      calculation of the ratio of neutrophils with lymphocytes. RESULTS: The mean NLR
      value of the control group and patients was 1.90+/-0.89 and 2.67+/-1.17,
      respectively (p<0.05). After a 3-month course of treatment, the patient group had
      a mean NLR value of 1.8+/-0.7, which was significantly lower than pretreatment
      values (p<0.001). The post-treatment mean ESR, CRP, and BASDAI scores were
      significantly lower than mean baseline scores (p<0.001, p=0.007, p<0.001,
      respectively). Also, NLR was found to be correlated with BASDAI, ESR, and CRP
      (r=0.388, p<0.001; r=0.455, p<0.0001; and r=0.3389, p<0.005, respectively).
      CONCLUSION: Neutrophil lymphocyte ratio could be a reliable and easily accessible
      method for follow-up of patients with AS.

PMID- 27708889
TI  - Body composition in patients with rheumatoid arthritis is not different than
      healthy subjects.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased risk of
      cardiovascular disease (CVD). Increased body fat, particularly its central
      distribution, is a well-known risk factor for CVD. A change in body composition
      in RA has been described previously. However, in most of these studies, age- and
      sex- but not body mass index (BMI)-matched controls were used. The aim of this
      study was to evaluate body composition in RA patients and compare it with age-,
      sex-, and BMI-matched controls. MATERIAL AND METHODS: Sixty-five RA patients (55
      females and 10 males; mean age 54.9 +/- 10.8) and 31 healthy controls (25
      females, 6 males; 53.8+/-8.6) were included in this study. Mean disease duration
      was 9.2+/-9.6 years. Body composition was assessed by anthropometric methods
      (skinfold thicknesses, body circumferences), bioimpedance analysis, and dual
      energy X-ray absorptiometry (DXA). Visceral adipose tissue (VAT) was assessed
      with computed tomography. RESULTS: There were no significant differences for
      total body fatness, regional fat distribution, and total body water and fat-free
      mass between RA patients and control subjects. Bone mineral content (BMC),
      assessed by DXA, was significantly lower in RA patients (p=0.004). Clinical
      disease activity indices and steroid treatment do not affect soft tissue body
      composition or BMC. CONCLUSION: At least some RA patients do not have soft tissue
      composition alterations and may have similar health risks in comparison with
      subjects with similar age, sex, and total adiposity.

PMID- 27708891
TI  - Bilateral coxitis in scleroderma-polymyositis overlap syndrome.
AB  - Joint manifestations in scleroderma (Scl) and polymyositis (PM) are dominated by
      inflammatory arthralgia. Arthritis is less common and preferentially affects the
      hands, wrists, knees, and ankles. Involvement of the hip has been rarely reported
      in the literature. We report a case of coxitis diagnosed in a patient suffering
      from scleroderma-polymyositis overlap syndrome successfully treated by ultrasound
      guided infiltration of triamcinolone hexacetonide.

PMID- 27708892
TI  - Presentation of three cases followed up with a diagnosis of Felty syndrome.
AB  - An effective treatment strategy for Felty syndrome (FS) has not been developed so
      far. In this article, three cases with FS, who responded to different treatment
      modalities, have been presented. Case 1 was a 52-year-old male patient who
      initially received methotrexate, and then, he was switched to granulocyte colony
      stimulating factor (G-CSF) and cyclosporine treatment when his neutropenia was
      further deteriorated. The patient needed monthly doses of G-CSF for nearly 6
      months, and his steroid dose was increased. Afterwards, his neutropenia improved
      with cyclosporine, methotrexate, and hydroxychloroquine combination treatment.
      Case 2 was a 78-year-old female patient who was started on leflunomide,
      hydroxychloroquine, and 60 mg methylprednisolone. Case 3 was a 69-year-old female
      patient who was first treated with 32 mg methylprednisolone, G-CSF, and then with
      cyclosporine. Neutropenia of both patients improved, and their health status
      normalized at 2 months. Different treatment strategies have been tried for the
      management of FS; disease-modifying anti-rheumatic drugs have been used
      successfully alone or in combination with G-CSF. As seen in the last case, it
      should be kept in mind that patients can present predominantly with symptoms of
      infection or hematologic disorders.

PMID- 27708890
TI  - Skin imaging in systemic sclerosis.
AB  - Fibrotic involvement of the skin is a cardinal feature of systemic sclerosis
      (SSc). The extent of skin involvement is associated with internal organ
      involvement, coinciding with more severe disease course and poor prognosis. A
      palpation-based semi-quantitative score, the modified Rodnan skin score, is
      widely used for the assessment of skin involvement, but it is entailed by
      significant limitations. More objective approaches to measure skin involvement
      employing imaging have been explored continuously in the past decades and are
      currently advancing. Here, we review the use of different imaging techniques for
      the assessment of skin involvement in patients with SSc, focusing mainly on
      ultrasound, magnetic resonance imaging, and optical coherence tomography.

PMID- 27708893
TI  - An unusual manifestation in a patient with adult-onset Still's disease: Minimal
      glomerular lesion.
AB  - Adult-onset Still's disease (AOSD) is a multisystem inflammatory disease of
      unknown etiology. It is characterized by arthritis, hectic fever, transient rash
      and visceral lesions such as pleuropericarditis, lymphadenopathy and hepato
      splenomegaly. Although kidney involvement may appear in some cases of AOSD,
      minimal glomerular lesion (MGL) has not been described. We describe a female
      patient, who presented with multisystemic manifestations, including high spiking
      fever, arthralgias, striking hyperferritinemia, and proteinuria. Renal biopsy
      showed classic MGL. A diagnosis of AOSD was made on the basis of Yamaguchi's
      criteria. The patient was treated with steroids, resulting in remission of the
      rheumatological condition closely paralleled by remission of proteinuria, thereby
      strongly suggesting a causative link between AOSD and MGL in this patient. Renal
      involvement in the AOSD was rarely reported in the literature. MGL may be a cause
      of unexplained proteinuria in AOSD. In this situation, renal biopsy is necessary
      to establish a definitive diagnosis.

PMID- 27708894
TI  - Etanercept in the treatment of SAPHO syndrome: Which place?
AB  - Synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (SAPHO) is a
      rare disease combining skin, bone, and joint manifestations. Its treatment
      remains a debated issue in the absence of a valid therapeutic strategy. The
      experience with tumor necrosis factor alpha (TNF alpha)-blocking agents is still
      small but encouraging. This therapy is reserved for refractory cases. The most
      commonly used agent is infliximab. Only few cases treated by etanercept have been
      reported in the literature. We report a new case treated by this biologic therapy
      and discuss its place in the treatment of SAPHO syndrome. A 30-year-old male,
      with a history of left clavicular osteitis that required surgical bone biopsy to
      rule out infection and malignancy, was admitted to the rheumatology department
      because of recurrent anterior chest pain, lower limb arthralgia, and sacroiliac
      pain. Laboratory findings revealed an inflammatory syndrome. Conventional
      radiography and computed tomography (CT) scan of the sternocostoclavicular region
      showed sclerosis and hyperostosis of the left clavicle. Right sacroiliitis was
      diagnosed based on the radiographic findings. Moreover, the patient reported
      palmoplantar pustulosis, thereby strengthening the diagnosis of SAPHO syndrome.
      As conventional treatment based on methotrexate, corticosteroids, and zoledronic
      acid was not effective, etanercept was initiated with good and rapid clinical and
      biological improvement. The diagnosis and treatment of SAPHO syndrome are
      challenging due to the heterogeneity of symptoms and unknown pathogenesis.
      Etanercept can be an effective therapy, especially in refractory cases. Further
      studies are needed in order to establish a therapeutic strategy.

PMID- 27708896
TI  - Inflammatory back pain due to heterotopic ossification.

PMID- 27708895
TI  - Mesalamine-induced refractory fever and progressive increase in creatinine level
      and leukocyte count in a patient with enteropathic arthritis.

PMID- 27708897
TI  - Articular and abarticular manifestations in type 2 diabetes mellitus.
AB  - OBJECTIVE: Diabetes mellitus (DM), a worldwide high-prevalence disease, is
      associated with a large variety of rheumatic manifestations. It affects the
      connective tissues in many ways and causes alterations in the periarticular and
      the musculoskeletal systems. In most cases, these manifestations are associated
      with functional disability and pain, affecting the quality of life of the
      diabetic patient. The aim of our study is to review the different articular and
      abarticular manifestations in diabetic patients and the associated factors of
      these rheumatic manifestations. MATERIAL AND METHODS: A cross-sectional study
      that includes all patients suffering from type 2 DM who present with articular or
      abarticular manifestations. RESULTS: We included 116 diabetic patients presenting
      with articular or abarticular manifestations. Our study showed four important
      findings. First, a large variety of articular and abarticular manifestations were
      present in patients with type 2 DM. Second, osteoarthritis (OA) of the knee was
      the most frequent articular manifestations. It was seen in 49% of our patients.
      Third, the most common manifestations in diabetic Moroccan patients were carpal
      tunnel syndrome (CTS), adhesive capsulitis of the shoulder, and diabetic
      cheiroarthropathy (29%, 23%, and 16%, respectively). Fourth, there was a
      significant association between vascular complications and the development of
      articular and abarticular manifestations. CONCLUSION: This study shows that the
      articular and abarticular manifestations in diabetic Moroccan patients are
      dominated by CTS, adhesive capsulitis of the shoulder, and diabetic
      cheiroarthropathy, with a significant association between vascular complications
      and the development of some of these manifestations.

PMID- 27708898
TI  - Potential role of interleukin-18 in patients with rheumatoid arthritis-associated
      carotid intima-media thickness but not insulin resistance.
AB  - OBJECTIVE: Plasma interleukin-18 (IL-18) has been reported to be associated with
      homeostasis model assessment of insulin resistance (HOMA-IR). It also has been
      described as one of the factors that, in addition to insulin resistance, may also
      contribute to atherosclerosis. Parameters of systemic inflammation are also
      significantly associated with circulating IL-18. Our objective was to investigate
      whether IL-18 is associated with insulin resistance and atherosclerosis in
      patients with rheumatoid arthritis (RA) in which accelerated atherogenesis
      develops. MATERIAL AND METHODS: Fifty-one female RA patients and 30 female
      controls were enrolled in the study; 31 of them were without disease-modifying
      antirheumatic drug (DMARD) treatment and had a relatively short disease duration.
      Disease activity was assessed by Disease Activity Score (DAS) 28 index. HOMA-IR
      method was used to detect insulin resistance. Erythrocyte sedimentation rate
      (ESR), C-reactive protein (CRP), fasting plasma glucose (FPG), insulin, tumor
      necrosis factor alpha (TNF-alpha), and IL-18 levels were evaluated. Also, carotid
      intima-media thickness (cIMT) was measured. RESULTS: There were no differences
      between patients and the control group according to age, sex, and body mass
      index. ESR, CRP, insulin, FPG, HOMA-IR, TNF-alpha, IL-18 levels, and cIMT
      measurements were significantly high in the patient group. HOMA-IR and cIMT
      measurements were similar and high in both the DMARD and non-DMARD patient
      groups. HOMA-IR correlated with TNF-alpha (r=0.308, p=0.028), but no correlation
      was found between IL-18 and HOMA-IR. However, IL-18 was correlated positively
      with cIMT (r= 0.318, p=0.028) and negatively with BMI (r=-0.360, p=0.01).
      CONCLUSION: IL-18 is associated with atherosclerosis in RA patients. However, no
      significant relation was found with insulin resistance. IL-18 may be a marker for
      early evaluation of atherosclerosis in RA patients.

PMID- 27708899
TI  - Serum lipid changes and insulin resistance in familial Mediterranean fever.
AB  - OBJECTIVE: Inflammation is known to alter lipid profiles and to induce insulin
      resistance. This study was planned to test the hypothesis that familial
      Mediterranean ferver (FMF) patients and their first-degree asymptomatic relatives
      may have lipid profile changes and/or insulin resistance, similar to other
      inflammatory diseases. MATERIAL AND METHODS: We studied 72 FMF patients, 30
      asymptomatic first-degree relatives, and 75 healthy controls. Fasting and 2-hour
      postprandial glucose, insulin, apolipoprotein (Apo) A1, Apo B, acute phase
      reactants, and lipid profiles of all subjects were studied. Insulin resistance
      was determined by the HOMA (Homeostasis Model Assessment) index. RESULTS: There
      was no difference between the groups with regard to sex, mean systolic and
      diastolic blood pressure, body mass index, smoking status, fasting and
      postprandial 2-hour glucose, insulin, acute phase reactants, and HOMA index
      levels. High-density lipoprotein cholesterol (HDL-C) levels were similar between
      FMF patients and FMF relatives (48.9+/-12.4 mg/dL vs 49.3+/-13.8 mg/dL; p=NS),
      and both were lower than controls (48.9+/-12.4 mg/dL vs 59.6+/-15.1 mg/dL;
      p<0.001 and 49.3+/-13.8 mg/dL vs 59.8+/-15.1 mg/dL; p=0.001, respectively). Apo
      A1 levels in FMF patients and asymptomatic first-degree FMF relatives were both
      lower than in controls, similar to the HDL-C levels (126.1+/-25.7 mg/dL vs
      151.2+/-31.4 mg/dL; p<0.001 and 129.5+/-29.0 mg/dL vs 151.2+/-31.4 mg/dL;
      p=0.002, respectively). TG levels were significantly higher in FMF relatives as
      compared to controls (113.4+/-53.6 mg/dL vs 97.1+/- 54.9 mg/dL; p=0.025).
      CONCLUSION: Low HDL-C and low Apo A1 levels are found in FMF patients and their
      first-degree asymptomatic relatives. Low-grade inflammation caused by MEFV
      mutations may be responsible for these lipid profile changes.

PMID- 27708900
TI  - New platelet indices as inflammatory parameters for patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To test new platelet indices for patients with rheumatoid arthritis
      (RA) as new acute phase reactants. MATERIAL AND METHODS: In total, 120 patients
      with RA and 40 patients in the control group were analyzed. A DAS 28 score over
      2.6 was accepted as active disease, and a DAS 28 score lower than 2.6 was
      accepted as under remission. Platelet distribution width, plateletcrit, and mean
      platelet volume were analyzed for three groups: patients with active RA, patients
      under remission, and the control group. RESULTS: There were 72 patients with
      active disease and 48 patients under remission. The erythrocyte sedimentation
      rate (ESR), C-reactive protein (CRP), mean platelet volume (MPV), plateletcrit
      (PTC), and platelet distribution width (PDW) scores were all statistically
      different among groups. In our data, PTC was found to be a positive acute phase
      reactant and others were negative acute phase reactants for patients with RA.
      CONCLUSION: These new indices are cheap, widely available, and useful parameters
      for routine clinical rheumatology practice.

PMID- 27708901
TI  - Combined infliximab and methotrexate treatment improves the depressive state in
      rheumatoid arthritis patients more effectively than methotrexate alone.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) patients have a greater depressive tendency
      than normal subjects, and infliximab is known to provide quick therapeutic
      effects and to have high bioavailability for RA. We therefore investigated
      whether the depressive state of RA patients would be improved by infliximab.
      MATERIAL AND METHODS: The Self-Rating Depression Scale (SDS) was used to evaluate
      34 RA patients before and 14 or 30 weeks after inflixi mab treatment using the
      SDS and Disease Activity Score (DAS) 28. The SDS and DAS28 results before and
      after treatment were compared. RESULTS: We also included 42 cases treated with
      methotrexate as the control group. The SDS decreased in both groups, and the
      intraindividual vari ability was p<0.001, indicating that the drugs had
      significantly different effects on the SDS. The DAS tended to decrease in both
      groups, but the intraindividual variability was p=0.199, indicating no difference
      between the two drugs. CONCLUSION: This study is a preliminary study, but the
      data suggest that infliximab may reduce RA disease activity and improve the
      depressive state.

PMID- 27708902
TI  - On matters of causation in personal injury cases: Considerations in forensic
      examination.
AB  - Rheumatologists are often called to be independent examiners of injured claimants
      and to address the question: "What is causing the injured person's symptoms?"
      This article deals with the legal principles that arise in these cases, including
      causation, convenient focus, secondary gain, and thin skull rules. We shall first
      set out two hypothetical scenarios of personal injury cases that set the scene
      for a discussion of legal principles in personal injury law. With the same two
      scenarios of personal injury in mind, we shall review the legal principles and
      the biopsychosocial models of the illnesses concerned and consider the importance
      of examiners going beyond diagnostic labels towards a more in-depth analysis of
      illness factors and mechanisms that in turn assist the trier of facts.

PMID- 27708903
TI  - Acute coronary syndrome in Behcet's disease caused by a coronary artery aneurysm
      and thrombosis.
AB  - Behcet's disease (BD) is a multisystemic vasculitis that can involve vessels of
      all sizes and is characterized by recurrent oral and genital ulcers with variable
      manifestations affecting the skin, eyes, and central nervous and musculoskeletal
      systems. Vascular involvement in BD is reported to be up to 40% in different
      series. The abdominal and thoracic aorta and pulmonary and femoral arteries are
      the most commonly involved arteries. However coronary arteries are rarely
      affected. Herein, we present a 29-year-old man who was consulted with progressive
      severe chest pain of 3 days in duration to our clinic. The patient was diagnosed
      with BD with mucocutaneous symptoms and a positive pathergy test 1 year ago and
      was in clinical remission for the last 6 months. At the first evaluation in the
      emergency department, the patient's vital signs were stable, whereas he had
      elevated troponin T levels with a normal electrocardiogram and hypokinetic areas
      in the apex of the heart in the echocardiography. Conventional and computed
      tomography coronary angiography revealed aneurysms and intramural thrombosis in
      the left anterior descending and right coronary arteries. Although ischemic
      symptoms and signs improved with anticoagulant and antiaggregant therapies,
      coronary aneurysms were observed to increase in size. Immunosuppressive (IS)
      treatment was started with pulse intravenous corticosteroids and
      cyclophosphamide. Because of the high re-stenosis risk, stents were not applied
      to the affected vessels during the acute thrombosis period. During routine
      investigations, an in situ pulmonary thrombosis was also detected bilaterally in
      the peripheral pulmonary arteries. In conclusion, coronary artery aneurysm is a
      rare and poor prognostic manifestation of BD. The treatment protocol for these
      aneurysms is not well clarified. IS therapies are definitely indicated, but the
      role of anticoagulants and invasive vascular interventions is controversial.

PMID- 27708904
TI  - Spontaneous patellar tendon rupture in a case followed up for diagnosis of
      systemic lupus erythematosus.
AB  - Spontaneous patellar tendon rupture is a rare condition that usually occurs
      secondary to conditions, such as rheumatoid arthritis, systemic lupus
      erythematosus (SLE), and use of steroids and fluoroquinolones. This paper
      presents a full-thickness patellar tendon rupture detected with magnetic
      resonance imaging, which was performed due to pain and swelling that started
      spontaneously on the front side of the left knee without a history of any trauma,
      of a 35-year-old male patient who had been followed up for a diagnosis of SLE for
      approximately 4 months and who had started taking methylprednisolone 4 mg/day 4
      months prior, used it for 1 month, and then stopped using it. In patients who are
      followed up for a diagnosis of SLE, it should be kept in mind that there is a
      risk of developing a spontaneous tendon rupture secondary to chronic inflammation
      and use of corticosteroids.

PMID- 27708905
TI  - Chondrodermatitis nodularis chronica helicis in a patient with systemic sclerosis
      associated with primary biliary cirrhosis (Reynolds syndrome): A case report.
AB  - Chondrodermatitis nodularis chronica helicis is a rare non-neoplastic
      inflammatory and degenerative process of the external ear, characterized by
      necrobiotic changes in the dermis that extend down to the perichondrium. This
      condition has been occasionally reported in patients with limited cutaneous
      systemic sclerosis but not in those with concomitant primary biliary cirrhosis;
      this association is known as Reynolds syndrome. We report a 70-year-old woman
      diagnosed with primary biliary cirrhosis at age 47 and with limited cutaneous
      systemic sclerosis at age 54 who developed a painful ulcerated nodule on the
      helical rim of the left ear shortly after the last diagnosis. The lesion was
      excised because of the suspicion of malignancy, but the histopathology was
      consistent with chondrodermatitis nodularis chronica helicis. Although this
      condition is infrequent, it is necessary to know, because it may occur in
      patients with systemic sclerosis and be mistaken for neoplasms, such as basal
      cell and squamous cell carcinoma, and these patients have an increased risk for
      the development of skin malignancies.

PMID- 27708906
TI  - A successful treatment of juvenile idiopathic arthritis with rituximab: A report
      of two cases.
AB  - Juvenile idiopathic arthritis (JIA) is defined as arthritis of unknown cause that
      starts before 16 years of age and lasts at least 6 weeks. It is the most common
      chronic inflammatory disease in childhood and often persists through adulthood
      and can lead to severe disability. Biologics are an important therapeutic option
      for treating patients with JIA. The efficiency of rituximab has not been proven
      for this indication. Its use has rarely been reported in the literature. We
      report two new cases of severe and refractory polyarticular JIA with positive
      rheumatoid factor affecting two African females aged 17 and 18 years successfully
      treated with rituximab. According to our experience, the use of rituximab in the
      treatment of JIA, especially in severe polyarticular forms with positive
      rheumatoid factor, might be a good alternative. Larger therapeutic trials should
      be conducted in this direction in order to prove the effectiveness of this
      biotherapy for this indication.

PMID- 27708907
TI  - Severe candida laryngitis in a patient with rheumatoid arthritis treated with
      adalimumab.
AB  - Rheumatoid arthritis is a chronic erosive rheumatic disease that can present with
      polyarticular involvement. Anti-TNF-alpha drugs are used in cases that are
      resistant to traditional disease-modifying antirheumatic drugs (DMARDs). Anti-TNF
      alpha drugs are groundbreaking drugs, the efficacy of which has been proven in
      the treatment of rheumatoid arthritis. However, the data concerning safety remain
      limited and contradictory. The risk of tuberculosis reactivation, various
      infections, as well as lymphoproliferative disease and/or secondary malignancy is
      a matter of discussion. In this report, we report a 52-year-old male patient
      using adalimumab for active rheumatoid arthritis who presented to our polyclinic
      with generalized mouth and throat sores, hoarseness, and swallowing difficulty.
      Candida laryngitis was detected in the laryngoscopy and culture samples.
      Adalimumab was discontinued, and the infection was controlled with anti-fungal
      treatment.

PMID- 27708908
TI  - A case of neutrophilic dermatosis who develop palpable purpura during the use of
      montelukast.
AB  - In this case report, we present a female patient with neutrophilic dermatosis
      (ND) occurring as palpable purpura after using montelukast. Neutrophilic
      dermatoses (NDs) are characterized by skin lesions in which mature neutrophils
      are predominantly located in the epidermis and dermis in the absence of any
      infective pathology. Classification of the NDs is based upon the recognition of
      clinical and pathologic features, as well as the identification of associated
      diseases, like Sweet's syndrome, pyoderma gangrenosum, generalized pustular
      psoriasis, and Behcet's disease. Cutaneous findings in NDs are variable and can
      include vesiculopustules, plaques, nodules, or ulcerations. Drug-induced NDs are
      not uncommon, but ND with palpable purpura is uncommon. The current patient
      appeared with a rare presentation as palpable purpura without vasculitis
      regarding ND. It is important that this is the first case report.

PMID- 27708909
TI  - Familial Mediterranean fever and demyelinating plaques in the central nervous
      system.

PMID- 27708910
TI  - Role of PET/CT in the diagnosis of large vessel vasculitis in a patient with
      systemic inflammatory response syndrome.

PMID- 27708911
TI  - Is early diagnosis of pulmonary arterial hypertension possible in inflammatory
      rheumatic diseases? Experience from a single center in Turkey.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a devastating complication of
      inflammatory rheumatic diseases. The aim of this study was to determine the role
      of screening for the early diagnosis of pulmonary hypertension (PH) in
      inflammatory rheumatic diseases. MATERIAL AND METHODS: Data of patients with
      inflammatory rheumatic diseases and PH who had no obvious cause of PH and who
      were evaluated by Working Group for Pulmonary Hypertension in Hacettepe
      University were investigated retrospectively. All patients with inflammatory
      disease were evaluated by right heart catheterization (RHC) to check if they had
      systolic pulmonary arterial pressure (sPAP) >=40 mmHg and/or symptoms related to
      PH unless explained by other causes. RESULTS: RHC was performed in 47 patients
      with inflammatory rheumatic diseases and PH out of 50 patients who were to be
      evaluated by RHC based on clinical and Doppler echocardiographic findings. There
      was a positive correlation between sPAP estimated by Doppler echocardiography and
      sPAP determined by RHC in patients with inflammatory rheumatic diseases (r=0.66;
      p<0.001). The mean pulmonary arterial pressure (mPAP) was found to be <25 mmHg in
      27.7% of the patients. New York Heart Association functional capacity (NYHA FC)
      was class III or IV in 79.0% of the patients with PAH. PAH was more frequent in
      patients with NYHA FC III-IV compared with patients with NYHA FC I-II [58.7% (15)
      patients vs. 19.0% (4) patients; p=0.009]. CONCLUSION: In this study,
      approximately 80% of the patients with inflammatory disease-associated PAH were
      diagnosed late in NYHA FC III or IV. There are still unresolved issues in the
      diagnosis and treatment of PH in inflammatory diseases. Collaboration and
      multidisciplinary approach are the key points to overcome the challenges in this
      field.

PMID- 27708912
TI  - Humor in systemic lupus erythematosus.
AB  - OBJECTIVE: Humor has neurophysiological effects influencing the release of
      cortisol, which may have a direct impact on the immune system. Laughter is
      associated with a decreased production of inflammatory cytokines both in the
      general population and in rheumatoid arthritis (RA). Our objective was to explore
      the effects of humor on serum cytokines [particularly interleukin-6 (IL-6)] and
      cortisol levels in systemic lupus erythematosus (SLE), after a standard
      intervention (120 min of visual comedy). MATERIAL AND METHODS: We enrolled 58
      females with SLE from consecutive patients assessed in the Montreal General
      Hospital lupus clinic. The subjects who consented to participate were randomized
      in a 1:1 ratio to the intervention (watching 120 min of comedy) or control group
      (watching a 120 min documentary). Measurements of cytokine and serum cortisol
      levels as well as 24-h urine cortisol were taken before, during, and after the
      interventions. We compared serum cytokine levels and serum and 24-h urine
      cortisol levels in the humor and control groups and performed regression analyses
      of these outcomes, adjusting for demographics and the current use of prednisone.
      RESULTS: There were no significant differences between the control and humor
      groups in demographics or clinical variables. Baseline serum levels of IL-6, IL
      10, tumor necrosis factor-alpha, and B-cell activating factor were also similar
      in both groups. There was no evidence of a humor effect in terms of decreasing
      cytokine levels, although there was some suggestion of lowered cortisol secretion
      in the humor group based the 24-h urinary cortisol levels in a subgroup.
      CONCLUSION: In contrast to what has been published for RA, we saw no clear
      effects of humor in altering cytokine levels in SLE, although interesting trends
      were seen for lower cortisol levels after humor intervention compared with the
      control group.

PMID- 27708913
TI  - Early detection of spondyloarthropathy in patients with psoriasis by using the
      ultrasonography and magnetic resonance image.
AB  - OBJECTIVE: To assess the validity of ultrasound (US) in the early detection of
      arthritis and enthesitis, with assessment of the validity of magnetic resonance
      imaging (MRI) in the early detection of sacroiliitis and spondylitis in patients
      with psoriasis and to compare the findings of clinical examination and
      conventional radiography. MATERIAL AND METHODS: The study included 50 patients
      with psoriasis and 20 healthy controls. All patients and controls underwent US
      and power Doppler analyses for the joints of both hands and feet and the
      entheseal sites. MRI of the lumbosacral spine and sacroiliac joints was
      performed. RESULTS: Abnormal US findings of arthritis were present in 18%
      patients, whereas only 6% patients had X-ray abnormalities, the enthesopathy
      represent 74%, at a higher percentage than clinical and radiological assessment
      (46, 26% respectively). MRI and radiological study demonstrated evidence of
      inflammation in the spine in 44% and 16% patients, respectively, and evidence of
      sacroiliitis in 10% and 6% patients, respectively. CONCLUSION: Use of newer
      imaging modalities allows early diagnosis and early initiation of therapy.

PMID- 27708914
TI  - Clinical utility of bone scintigraphy in patients with limb pain of suspected
      musculoskeletal origin.
AB  - OBJECTIVE: To determine the clinical utility of bone scintigraphy in patients
      with limb pain of suspected musculoskeletal origin. MATERIAL AND METHODS: All
      patients aged >=18 years who were referred for diagnosis and management of limb
      pain were diagnosed on the basis of history, physical examination, and
      investigations excluding bone scintigraphy. After the presumptive diagnosis was
      made (the pre-test diagnosis), all subjects underwent bone scintigraphy, or if
      they had a previous bone scintigram for their pain condition, the results of that
      scintigram were reviewed. Then, the pre-test diagnosis was reviewed in light of
      the bone scintigraphy findings and repeat clinical assessment as needed. The post
      test diagnosis was considered either as unchanged diagnosis or changed diagnosis
      for the region or regions of interest. RESULTS: There were 118 females (54.8%)
      and 97 males (45.2%). The mean age of the entire group was 36+/-8.1 years (range:
      18-87 years). The mean duration of the symptoms was 17.4+/-11.2 months (range: 1
      264 months). Of the 215 subjects, 212 had a bone scintigram. Of these 212
      subjects, none had a changed diagnosis. CONCLUSION: In the evaluation of limb
      pain of suspected musculoskeletal origin, scintigraphy is unlikely to alter the
      pre-test diagnosis or affect treatment decisions after history, physical
      examination, and non-scintigraphic investigations. The clinical utility of
      scinitigraphy in this setting is low.

PMID- 27708915
TI  - Neutrophil-lymphocyte ratio in children with familial Mediterranean fever:
      Original article.
AB  - OBJECTIVE: The aim of present study was (a) to evaluate the relationship between
      the neutrophil/lymphocyte (N/L) ratio and mutation types of familial
      Mediterranean fever (FMF) in children and (b) to evaluate the relationship
      between the N/L ratio and age. MATERIAL AND METHODS: Three hundred forty-three
      children with familial Mediterranean fever in the attack-free period and 283
      healthy control children were included in the study. Patients were divided into
      subgroups according to mutation types. Neutrophil and lymphocyte counts were
      retrieved from medical records of patients and the N/L ratio was calculated from
      these parameters. RESULTS: The N/L ratio of patients was found to be
      significantly higher than that of controls (p<0.001). Among 343 patients,
      homozygous, heterozygous, and compound mutations were observed in 39, 253, and 51
      patients, respectively. The differences in the N/L ratio among patients with
      homozygous, heterozygous, and compound mutations were not statistically
      significant. The most common mutations were M694V (n=126), E148Q (n=70), M680I,
      (n=33), and V726A (n=28). Significant differences were not observed among these
      mutations in terms of the N/L ratio (p>0.05). In all subjects, there was a weak
      but significant relationship between age and the N/L ratio (r: 0.215, p<0.001).
      CONCLUSION: The N/L ratio, which can be determined by simple methods in routine
      blood tests, may be used for the follow-up monitoring of chronic inflammation in
      patients. In addition, the N/L ratio may give an idea to clinicians regarding the
      early initiation of treatment in patients with typical clinical findings of FMF.

PMID- 27708917
TI  - Tuberculous bursitis of the greater trochanter mimicking ankylosing spondylitis.
AB  - Tuberculous trochanteric bursitis (TTB) is a rare condition that accounts for 1%
      of musculoskeletal tuberculosis cases. Extrapulmonary TB is usually diagnosed
      late because of reduced diagnostic suspicion, particularly in the absence of
      signs of systemic infection. Herein, we report a case of right hip pain that was
      misdiagnosed as ankylosing spondylitis. The patient had a history of inflammatory
      back pain with morning stiffness. However, HLA-B27 was negative. Sacroiliac
      magnetic resonance imaging (MRI) revealed a giant multiloculated collection
      (27*16*10 cm). Percutaneous drainage was performed and Mycobacterium tuberculosis
      was observed in fluid culture. The patient was treated by drainage along with
      antituberculosis therapy. After 1 year of antituberculosis therapy, control MRI
      revealed total resolution of the large fluid collection. It is important to
      emphasize that fever or general symptoms are absent in patients with TTB, as
      observed in the present case. In endemic countries, TTB should be kept in mind in
      the differential diagnosis of a patient presenting with chronic hip pain without
      fever, weight loss, and constitutional symptoms.

PMID- 27708918
TI  - An unusual cause of medial foot pain: The cornuate navicular.
AB  - The accessory navicular bone (ANB) is a secondary ossification center of the
      navicular bone and is rarely observed. Three distinct types of accessory
      navicular bones have been described. The type III, known as the cornuate
      navicular, is a rare morphological entity of the accessory navicular bone. We
      report the case of a patient, 48 years old, who presented with chronic swelling
      and pain in her left foot. Radiological examination permitted the diagnosis and
      showed a conflict between the tibial posterior tendon and the cornuate navicular,
      responsible for the symptoms. Surgical treatment led to symptoms relief.

PMID- 27708916
TI  - Recent advances in Takayasu's arteritis.
AB  - Takayasu's arteritis (TAK) is a rare, chronic large-vessel vasculitis (LVV) that
      predominantly affects the aorta, its major branches, and the pulmonary arteries.
      Recent advances in the diagnosis, clinical course, disease assessment with
      biomarkers/imaging and new clinical tools, patient-reported outcomes, and new
      treatment options of TAK are discussed in this review. Conventional angiography,
      the gold standard method for initial diagnosis, appears to have been replaced
      with new imaging modalities such as magnetic resonance angiography (MRA) and 18F
      fluorodeoxyglucose positron emission tomography (FDG-PET) in recent years. MRA
      and FDG-PET are also promising for the assessment of disease activity. New tools
      for disease assessment such as Indian Takayasu's Arteritis Score 2010 (ITAS2010)
      and color Doppler ultrasound (CDUS) aim to better characterize and quantify
      disease activity; however, different imaging modalities in routine follow-up are
      not incorporated sufficiently in these approaches. Prognosis is possibly getting
      better, with lower mortality in recent years; however, it is difficult to assess
      the widely different vascular intervention rates among the clinical series.
      Leflunomide, tumor necrosis factor (TNF)-alpha antagonists, and tocilizumab are
      new options for patients resistant to conventional therapies. There is a clear
      need to develop a validated set of outcome measures for use in clinical trials of
      TAK. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group has
      taken on this task, finished a Delphi exercise with experts, and aims to develop
      a core set of outcomes for LVV in accordance with OMERACT Filter 2.0.

PMID- 27708919
TI  - Successful treatment of tumor necrosis factor receptor-associated periodic
      syndrome (TRAPS) with tocilizumab: A case report.
AB  - Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an
      autosomal dominant autoinflammatory disease linked to chromosome 12p13 and, more
      specifically, with mutations within the tumor necrosis factor receptor
      superfamily, member 1A gene (TNFRSF1A gene). It is characterized by the presence
      of fever, abdominal pain, myalgia, arthralgia or arthritis, and skin rash. In
      this report, we describe the case of a patient with tumor necrosis factor
      receptor-associated periodic syndrome (TRAPS) treated successfully with the anti
      interleukin-6 (anti-IL-6) receptor monoclonal antibody tocilizumab, while
      treatment with anti-TNF alpha etanercept and infliximab had both failed.

PMID- 27708920
TI  - Spinning-induced rhabdomyolysis: A case report and review of literature.
AB  - Rhabdomyolysis is a condition of skeletal muscle breakdown in which muscle injury
      causes a release of myoglobin and the muscle enzymes creatine phosphokinase
      (CPK), lactate dehydrogenase (LDH), and transaminases. Exertional rhabdomyolysis,
      which is precipitated by exercise or exertion, ranges from mild muscle injury
      with negligible symptoms or systemic effects to fulminant cases. Herein, we
      report a 26-year-old female patient who was admitted to our Physical Medicine and
      Rehabilitation outpatient clinics with severe bilateral thigh pain persisting for
      5 days after participating in a spinning class and diagnosed with exertional
      rhabdomyolysis. Timely diagnosis and treatment prevented the potentially life
      threatening consequences. We assume that it is essential to raise the awareness
      of this phenomenon not only by physicians but also by the community, since
      regular exercise and being physically active are increasingly encouraged in
      modern life.

PMID- 27708921
TI  - Methorexate therapy in a patient with rheumatoid arthritis complicated by
      idiopathic thrombocytopenic purpura.
AB  - The association of rheumatoid arthritis (RA) and immune thrombocytopenic purpura
      (ITP) has been reported rarely. Methotrexate, which is used for RA treatment,
      causes thrombocytopenia. Therefore, in medical practice, physicians avoid using
      methotrexate for RA in patients who have both RA and ITP. Here, we report an RA
      case that also had ITP, which did not decrease in platelet count after
      methotrexate therapy. A 50-year-old woman was diagnosed with diabetes mellitus in
      1990, RA in 1995, and ITP in 2000. She had received hydroxychloroquine for more
      than 5 years. She was treated with prednisolone 16 mg/daily between 2006 and
      2007, but she discontinued this therapy because of weight gain. Laboratory
      findings were not remarkable, except for thrombocytopenia. We started
      methotrexate therapy 10 mg per week for treatment of RA, and hydroxychloroquine
      therapy was stopped due to nonresponse. The methotrexate dose was increased up to
      15 mg/week. Her complete blood cell count was monitored frequently. We did not
      observe any decrease in platelet count, while active arthritis symptoms of the
      patient were relieved. This case shows that methotrexate may be used in patients
      diagnosed with RA that is associated with ITP under strict monitoring.

PMID- 27708922
TI  - Cutis laxa (elastolysis) in a patient with Sjogren's syndrome.

PMID- 27708923
TI  - Use of musculoskeletal ultrasound in rheumatoid arthritis in Turkey among
      rheumatologists: A national targeted ultrasound initiative survey.

PMID- 27708924
TI  - Computed tomography angiography (CTA) findings of lupus-associated intestinal
      vasculitis.

PMID- 27708925
TI  - A cross-sectional study of perceived injustice and disability in hip
      osteoarthritis.
AB  - OBJECTIVE: To determine the correlation among severity of hip osteoarthritis,
      disability, and Perceived injustice. MATERIAL AND METHODS: A cohort of 46
      participants with unilateral hip osteoarthritis underwent hip range of motion
      measurements and completed the Injustice Experience Questionnaire (IEQ), the Hip
      Disability and Osteoarthritis Outcome Score (HOOS), and a Croft radiological
      grading of osteoarthritis severity. RESULTS: The mean age of the cohort was
      62.7+/-10.4 years, and the cohort included 27 females. The mean duration of
      symptoms was 46.9+/-20.6 months. The means of each of the five subscales of the
      HOOS were as follows: Pain, 62.3+/-9.4; Other Symptoms, 56.7+/-9.6; Function in
      Activities of Daily Living (ADL), 58.2+/-6.7; Function in Sport and Recreation
      (Sport/Rec), 58.1+/-6.7; and Hip-Related Quality of Life (QOL) 59.9+/-7.5. The
      combined mean hip range of motion (abduction, adduction, flexion, extension,
      external rotation, internal rotation) was 215.9+/-10.9 degrees. The mean IEQ
      score (Perceived injustice) was 12.0+/-1.7. Of the available factors, only QOL,
      hip range of motion, and the Croft radiological osteoarthritis grade predicted
      Perceived injustice scores, with an R-squared of 0.81 in multiple regression
      analysis. CONCLUSION: In this cohort of patients with unilateral osteoarthritis,
      more severe disease (as measured by restricted range of motion and radiological
      severity) was highly correlated with higher levels of Perceived injustice.
      Perceived injustice may thus reflect an appropriate response to the severity of
      the disease and is thus more likely a result of the disease process and
      subsequent disability rather than a cause of disability.

PMID- 27708926
TI  - Prevalence and factors associated with self-medication in rheumatology in Sub
      Saharan Africa.
AB  - OBJECTIVE: We sought to determine the prevalence of and factors associated with
      self-medication in patients with rheumatic diseases. MATERIAL AND METHODS: An
      analytical cross-sectional study was conducted from February to July 2013 in the
      rheumatology department. We included all patients who consulted for a rheumatic
      disease during the study period and who gave their consent. RESULTS: In total,
      203 patients were included; of these, 146 patients (71.92%) had practiced self
      medication. Furthermore, 99 patients (48.8%) had practiced self-medication for
      rheumatologic problems. The mean age of the patients was 45.5 years (range: 18-75
      years). State officials accounted for 44.4% of patients. Eighty-one patients were
      schooled. Low back pain (29.29%) was the main reason for consultation, followed
      by polyarthralgia (12.12%). Using a visual analogue scale, the level of pain for
      which patients had used self-medication was rated as >70 out of 100 in 57.6% of
      patients. Fifty-five patients often self-medicated and 28 patients rarely. Drugs
      were bought from the pharmacy in 97% of cases. The main channel of self
      medication was word of mouth (43.4%). The drugs used were mainly anti
      inflammatory drugs (diclofenac: 54.54% and ibuprofen: 57.57%). Ten patients were
      unaware of the risks of self-medication. In multivariate analysis, sex, education
      level, and occupation were statistically associated with self-medication.
      CONCLUSION: Self-medication for a specific rheumatologic symptom appears less
      common than self-medication in general. The procedures for responsible self
      medication should be defined in Burkina Faso in order to minimize the risks.

PMID- 27708927
TI  - Sarcopenia in women with rheumatoid arthritis.
AB  - OBJECTIVE: To assess sarcopenia status in women with rheumatoid arthritis (RA).
      MATERIAL AND METHODS: Thirty female patients with RA and 30 female controls
      without RA were enrolled in this study. Sarcopenia status in patients with RA was
      evaluated by assessing body composition using dual X-ray absorptiometry (DXA). C
      reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were
      measured, and body mass index (BMI) and Disease Activity Score (DAS28) were
      calculated. Because sarcopenia differs between men and women, the study groups
      comprised only females. RESULTS: It was found that skeletal muscle index (SMI)
      was lower in patients with RA (5.83+/-0.807) than in controls (7.30+/-1.640).
      Sarcopenia (in females with an SMI of <=5.75 kg/m2) was more common in the RA
      group and the difference was statistically significant (p=0.004). Sarcopenia was
      more common in patients with RA who were normal or overweight than in those who
      were obese according to their BMI. There was no relationship between sarcopenia
      and DAS28 in the RA group (p=0.530), whereas CRP levels were significantly higher
      in patients with sarcopenia (p=0.230). No relationship was found between drug use
      and sarcopenia in the RA group. CONCLUSION: It was found that SMI was decreased
      and sarcopenia risk was elevated in patients with RA and the risk was higher in
      non-obese patients.

PMID- 27708928
TI  - Anti-cyclic citrullinated peptide and rheumatoid factor in patients with chronic
      hepatitis B and hepatitis B carriers.
AB  - OBJECTIVE: Rheumatoid factor (RF) positivity that may occur in a number of
      patients with hepatitis B (HBV) infection poses challenges in terms of
      differential diagnosis with rheumatoid arthritis (RA). On the other hand,
      antibodies to cyclic citrullinated peptide (anti-CCP) may prove to be an
      important marker for differential diagnosis of the two conditions. This study
      aimed to assess anti-CCP and RF positivity among patients with hepatitis B and
      rheumatoid arthritis. MATERIAL AND METHODS: Anti-CCP and RF seropositivity was
      assessed in 61 patients with HBV infection (32 patients with chronic hepatitis,
      29 patients with inactive HBV carrier status) and 40 patients with RA as the
      control group. RESULTS: RF positivity was found in 18.7% and 34.4% of the
      patients with chronic hepatitis B and inactive HBV carrier status, respectively.
      On the other hand, only one patient with chronic HBV had low positive anti-CCP.
      RF was positive in 24 (60%) and anti-CCP was positive in 26 (65%) patients among
      the 40 patients with RA. CONCLUSION: Anti-CCP may be helpful in the differential
      diagnosis between RA and chronic HBV infection or inactive HBV carrier status.

PMID- 27708929
TI  - Muscular hypertonicity: a suspected contributor to rheumatological manifestations
      observed in ambulatory practice.
AB  - OBJECTIVE: The objective of this retrospective study of non-inflammatory
      rheumatic disease patients was to investigate if the individuals clinically
      identified with muscular hypertonicity (MHT) had increased clinical
      manifestations compared with those of age- and gender-matched patients with the
      same disorders. MATERIAL AND METHODS: The MHT status was clinically identified in
      the rheumatologist's myofascial protocol examination as relatively increased
      passive resistance of relaxed muscle on a slow gentle stretch. Clinical and
      laboratory data were abstracted on a pre-coded form, including symptom and
      physical examination features, serum assays, and medications. RESULTS: The 19 MHT
      cases complained of greater subjective stiffness (p=0.010) and tiredness
      (p=0.018) at initial encounters and increased aching pain (p=0.049) and were
      prescribed more (p=0.003) mild narcotic analgesics than the 19 comparison
      patients. The cases had higher (p=0.027) serum creatine kinase levels, and
      patients with diffuse MHT had greater frequency of heavy (30+pack-years)
      cigarette smoking (p=0.002) than comparison subjects. Narcotic usage was also
      greater in cases with diffuse involvement. CONCLUSION: Non-inflammatory rheumatic
      disease patients with MHT had an overall similar profile as that of comparison
      patients but had greater musculoskeletal complaints, and those with diffuse
      involvement had greater narcotic usage. Further research, including quantitative
      measurements of muscle stiffness, are required to determine whether MHT is a
      documented entity associated with increased rheumatological manifestations.

PMID- 27708930
TI  - Erythema elevatum diutinum coexisting with ankylosing spondylitis.
AB  - A 43-year-old woman presented to our hospital with the complaint of a reddish
      purple rash on the extensor sides of her forearms. She had been diagnosed with
      ankylosing spondylitis 7 years ago. On physical examination, reddish-purple
      nodules were detected on the pretibial areas of both legs and extensor sides of
      both hands and forearms. Neutrophil, eosinophil, lymphocyte, and mixed-type
      leukocyte infiltration and erythrocyte extravasation were observed in skin
      biopsy. Erythema elevatum diutinum (EED) was diagnosed. For treatment,
      sulphasalazine, colchicine, and diclofenac were started. After 3 months of
      treatment, the lesions were healed. To the best of our knowledge, this is the
      first report of EED coexisting with ankylosing spondylitis.

PMID- 27708931
TI  - A severe case of systemic lupus erythematosus with increased pressure
      communicating hydrocephalus.
AB  - Normal/increased pressure hydrocephaly is an unusual manifestation of systemic
      lupus erythematosus (SLE), and the pathogenesis is still unclear. We report the
      case of an 18-year-old white female with severe refractory renal and pulmonary
      involvement who developed stupor during intensive immunosuppressive treatment.
      Enlarged ventricles on imaging and increased intracranial pressure with the
      exclusion of infectious and hemorrhagic/thrombotic processes suggested increased
      pressure communicating hydrocephalus associated with SLE. Few case reports are
      reviewed, and potential pathophysiologic mechanisms are discussed.

PMID- 27708932
TI  - Successful treatment of Acrodermatitis continua of Hallopeau associated with
      psoriatic arthritis with adalimumab.
AB  - Acrodermatitis continua of Hallopeau (ACH) is a rare form of pustular psoriasis,
      mainly affecting distal phalanges of hands and feet. Many therapeutic options
      exist; however, it tends to be resistant to treatment. We report a 26-year-old
      man presented with a very severe psoriatic arthritis associated with ACH.
      Although this patient was resistant to a first line treatment (glucocorticoids
      and methotrexate), a rapid and dramatic improvement was observed after adalimumab
      was introduced. The effectiveness and tolerance of the treatment were maintained
      during the 12-month period of follow-up. This is the first report of the efficacy
      of adalimumab on ACH in a patient presented with psoriatic arthropathy.

PMID- 27708933
TI  - Subscapular bursitis as a rare manifestation of dermatomyositis: a case report.
AB  - Dermatomyositis (DM) is characterized by proximal muscle weakness and
      characteristic skin rash. Pain is a less common feature and usually indicates
      inflammation of extramuscular structures such as fascia. Here we report a rare
      case of subscapular bursitis in a 48-year-old woman with DM. She initially
      presented with severe, sharp, stabbing pain in her right shoulder that worsened
      with shoulder movement. Magnetic resonance imaging (MRI) revealed inflammation in
      the right subscapular bursae. A few months later, the patient developed
      periungual erythema, Gottron's papules, and shawl sign with muscle pain in her
      thighs. DM was diagnosed based on the presence of interface dermatitis on skin
      biopsy and diffuse muscle inflammation on MRI. Bursitis and myalgia responded
      incompletely to nonsteroidal anti-inflammatory drugs but promptly to
      corticosteroids. Here we report a case of subscapular bursitis as a rare
      manifestation of DM. Pain in patients with DM may warrant physicians to evaluate
      for the presence of additional inflammatory processes in the perimuscular
      structures.

PMID- 27708934
TI  - High-dose intravenous immunoglobulin therapy for rapidly progressive interstitial
      pneumonitis accompanied by anti-melanoma differentiation-associated gene 5
      antibody-positive amyopathic dermatomyositis.
AB  - Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive
      amyopathic dermatomyositis (ADM) associated with rapidly progressive interstitial
      pneumonitis (RPIP) frequently has a poor prognosis and optimal treatment is not
      well defined. Here, we report a 62-year-old Japanese man with anti-MDA5 antibody
      positive ADM associated with RPIP presented with progressive shortness of breath,
      Heliotrope rash, Gottron's papules, arthralgia, and fatigue but no sign of muscle
      weakness. Laboratory investigation revealed serum levels of the following
      biomarkers: ferritin, 1393 ng/mL; Krebs von der Lungen-6, 1880 U/mL; and creatine
      kinase, 85 U/L. Computed tomography (CT) images showed diffuse ground-glass
      opacity in both lung fields. Because anti-MDA5 was positive, we made a diagnosis
      of ADM associated with RPIP and initiated treatment. Following five courses of
      combination therapy with prednisolone, cyclosporine A, and intravenous
      cyclophosphamide (IVCY), IVCY treatment was switched to high-dose intravenous
      immunoglobulin therapy (IVIg) because of the reactivation of interstitial
      pneumonia with an increased serum ferritin level. Additional treatment with IVIg
      improved RPIP, with normalization of anti-ADM antibody levels. Therefore, IVIg
      mayt be a new candidate treatment for anti-MDA5 antibody-positive ADM associated
      with RPIP.

PMID- 27708935
TI  - Ileum and colon perforations in a young patient with Behcet's disease.

PMID- 27708936
TI  - Rheumatoid arthritis in a patient with bilateral congenital aplasia of the
      thumbs.

PMID- 27708937
TI  - Ischemia-hyperpnea test is useful to detect patients with fibromyalgia syndrome.
AB  - OBJECTIVE: To demonstrate the prevalence of neuromuscular hyperexcitability in
      Fibromyalgia Syndrome (FMS) by electromyography ischaemia-hyperpnea test (IHT)
      and its correlation with clinical and clinimetric parameters. MATERIAL AND
      METHODS: One hundred and forty-five FMS patients underwent IHT to evaluate
      neuromuscular hyperexcitability and were evaluated for pain (numeric Rating Scale
      and Regional Pain Scale), tenderness (tender points), disability [Fibromyalgia
      Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ)], quality of
      life (QOL) [Short Form 36 (SF36)], mood [Hospital Anxiety and Depression Scale
      (HADS)], sleep [numeric rating scale (NRS)], and fatigue [Functional Assessment
      of Chronic Illness Therapy-Fatigue (FACIT)]. RESULTS: Of the 145 patients, 95
      were tested positive by IHT, and 33 and 17 patients were negative and borderline,
      respectively. By comparing the three groups, IHT positive patients had lower age
      and lower SF36 vitality (V), social activities (SA), and mental summary index
      (MSI) than negative patients (p<0.05). By comparing positive versus negative
      patients and by comparing positive and borderline patients versus negative
      patients, it was found that FACIT was higher, whereas age, SF36 V, SA, mental
      health (MH), and MSI were lower (p<0.05). CONCLUSION: FMS patients present a high
      prevalence of neuromuscular hyperexcitability, as assessed by IHT. IHT positive
      patients have poor QOL and higher fatigue than IHT negative patients. Thus, IHT
      positivity could identify FMS patients with a more severe disease.

PMID- 27708938
TI  - Overview of the publications of rheumatologists after the millennium.
AB  - OBJECTIVE: Scientific progress can be directly measured by the growth of the
      scientific archive. To our knowledge, there has never been a systematic
      evaluation of the number and properties of the publications of rheumatologists.
      In this paper, we aimed to evaluate the properties of these papers. MATERIAL AND
      METHODS: All papers that were published between 2000 and 2011 by at least one
      rheumatologist author and that were indexed in Science Citation Index Expanded
      were evaluated. For this purpose, we used the ISI web of knowledge web of science
      software. RESULTS: Original articles were the most common document type. Most of
      the papers were published in rheumatology journals. From the point of the number
      of published papers, the top 3 countries were United States, England, and
      Germany; the top 3 journals were Annals of Rheumatic Diseases, Rheumatology, and
      Arthritis and Rheumatism, and the top 3 institutes are Harvard University, Leiden
      University, and The Imperial College of Science, Technology. Moreover, the
      publications of rheumatologists increased annually between 2000 and 2011.
      CONCLUSION: This paper is an overview of the publications of rheumatologists
      between 2000 and 2011. The results indicate an increasing trend of scientific
      productivity for rheumatologists. The outcomes about countries, institutions, and
      journals are in concordance with the general medical publication trends. More
      than half of the publications written by rheumatologist were published by
      rheumatology journals. We consider only quantitative data about publications; new
      research is required to qualitatively evaluate the data.

PMID- 27708939
TI  - Genistein protects dermal fibrosis in bleomycin-induced experimental scleroderma.
AB  - OBJECTIVE: Genistein, a phytoestrogen, has anti-oxidant, anti-inflammatory, and
      anti-angiogenic properties. The aim of the present study is to evaluate the
      protective effect of genistein in bleomycin (BLM)-induced dermal fibrosis.
      MATERIAL AND METHODS: This study involved four groups of Balb/c mice (n=10 per
      group). Mice in three groups were administered BLM [100 MUg/day in 100 MUL
      phosphate-buffered saline (PBS)] subcutaneously for 4 weeks; the remaining
      (control) group received only 100 MUL/day of PBS subcutaneously. PBS or BLM was
      injected into the shaved upper back. Two of the BLM-treated groups also received
      genistein (1 or 3 mg/kg/day, subcutaneously, to the dorsal front of neck). At the
      end of the fourth week, all mice were sacrificed and blood and tissue samples
      were obtained. RESULTS: The BLM applications increased the dermal thicknesses,
      tissue hydroxyproline contents, alpha-smooth muscle actin-positive cell counts,
      and led to histopathologically prominent dermal fibrosis. The genistein
      treatments decreased the tissue hydroxyproline contents and dermal thicknesses,
      in the BLM-injected mice. CONCLUSION: Genistein has antifibrotic potential in BLM
      induced dermal fibrosis model. However, its therapeutic potentials on human
      scleroderma require evaluation in future studies.

PMID- 27708940
TI  - Frequency of dense fine speckled pattern in immunofluorescence screening test.
AB  - OBJECTIVE: The presence of antinuclear antibodies (ANA), directed against
      intracellular antigens, is a distinctive feature of systemic autoimmune rheumatic
      diseases (SARDs). The standard test for antinuclear antibody screening is the
      indirect immunofluorescence (IIF). Anti-dense fine speckled 70 (anti-DFS70)
      antibodies were initially identified as an ANA IIF pattern from a patient with
      interstitial cystitis, but they were later associated with various other
      conditions. The objective of the study was to determine the frequency of anti
      DFS70 antibodies in a cohort of patients undergoing routine ANA testing. MATERIAL
      AND METHODS: From January 2011 to January 2012, a total of 5800 serum samples
      were screened for ANA by IIF (Euroimmune AG, Lubeck, Germany). DFS pattern was
      searched. RESULTS: ANA were present in 1302 (22.4%) of all patients. There were
      16 (1.2%) anti-DFS70 antibody-positive patients. The number of females and males
      who have anti-DFS70 antibody was eleven and five, respectively. All of the
      samples presented a titer of >=1/320. There was one patient with SARD from the
      rheumatology department. Another 15 patients were from gastroenterology,
      endocrinology, and general internal medicine. CONCLUSION: Although a distinctive
      clinical association has not been reported, anti-DFS70 have been proposed as a
      significant biomarker for the exclusion of SARD. The present study is a
      preliminary study. There is a need for a reliable assay to ensure reactivity to
      DFS70 and screening large populations.

PMID- 27708941
TI  - Short-term effect of the combination of hyaluronic acid, chondroitin sulfate, and
      keratin matrix on early symptomatic knee osteoarthritis.
AB  - OBJECTIVE: In the last years, symptomatic slow-acting drugs for osteoarthritis
      (SYSADOA) have been vastly studied and have generated considerable interest among
      clinicians. SYSADOA are generally used as a ground therapy with the main
      rationale to reduce the consumption of nonsteroidal anti-inflammatory drugs
      (NSAIDs) and thus limit the related adverse events. MATERIAL AND METHODS: In this
      study, we evaluated the short-term effect of an oral combination of hyaluronic
      acid, chondroitin sulfate, and keratin matrix on early symptomatic knee
      osteoarthritis. Forty patients were treated for 1 month and were allowed to
      assume analgesics or NSAIDs if necessary. RESULTS: At 2 months, the mean
      reduction of the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) score was 36% (p<0.001), and the mean reduction of the WOMAC pains score
      was 40% (p<0.001). Only two patients reported a sporadic need to assume
      analgesics; no patient reported any side effect during the study period.
      CONCLUSION: This data demonstrates that the oral combination of hyaluronic acid,
      chondroitin sulfate, and keratin matrix is safe, well tolerated, and shows a
      rapid action reducing pain and improving joint function and stiffness in early
      symptomatic knee osteoarthritis.

PMID- 27708943
TI  - Propylthiouracil-induced alveolar hemorrhage.
AB  - Thionamide induced vasculitis is a multisystem disease. The patients may present
      with different clinical signs and findings due to organ involvement. These
      patients are almost always perinuclear antineutrophil cytoplasmic antibody
      (pANCA) or antimyeloperoxidase (MPO) positive. Clinical findings are not seen in
      all of the patients who are ANCA positive while using thionamide. Although
      symptoms usually resolve with drug discontinuation, some patients, however,
      require high-dose steroids, immunosuppressants, or plasmapheresis. We present
      here a case of alveolar hemorrhage induced by propilthiouracil (PTU) during
      treatment with PTU for Graves' disease; patients completely recovered with
      corticosteroid, cyclophosphamide, and plasmapheresis.

PMID- 27708942
TI  - Fatigue in rheumatic diseases.
AB  - Fatigue is a common and important problem in many diseases including
      rheumatologic illnesses, and it has a negative impact on health-related quality
      of life. Fatigue is described as having an impact on multiple aspects of a
      patient's life. There is a need for knowledge about causes of and treatments for
      fatigue to ensure that patient outcomes are improved. There are several effective
      treatment strategies available for fatigue including pharmacological and non
      pharmacological therapies. We aim to provide an overview of fatigue in
      rheumatologic disorders and some recommendations on its optimal management.

PMID- 27708944
TI  - Pulmonary tuberculosis presenting with oral aphthae.
AB  - Tuberculosis is caused by the Mycobacterium tuberculosis bacterium. Tuberculosis
      primarily affects the lungs. Patients mainly complain of cough, sputum, night
      sweating, weight loss, and fever. However, there may be cases of atypical
      presentations. Although aphthous mouth ulcers are mostly present in the oral
      cavity in primary tuberculosis patients, our literature search showed only one
      case report of pulmonary tuberculosis with oral aphthae. Here we report a case of
      a patient with pulmonary tuberculosis admitted to the hospital with the complaint
      of oral aphthae.

PMID- 27708945
TI  - Refractory anemia in systemic sclerosis: myelodisplastic syndrome.
AB  - Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized
      by small vessel vasculopathy, autoantibodies, and skin or visceral organ fibrosis
      (lung, oesophagus, kidney etc.) as a result of extracellular collagen deposition.
      The cancer risk is higher in many rheumatic diseases, including SSc. Various
      defined malignancies may develop in 3%-11% of patients with SSc. These solid
      tumors are generally observed in the lung, oesophagus, or breast. In addition, an
      increased risk for hematological cancers were reported in literature. Herein, we
      describe an interesting case of SSc complicated by myelodisplastic syndrome
      (MDS). Our aim is to draw attention to developing cancers and the rare occurence
      of MDS in patients with SSc.

PMID- 27708947
TI  - Magnetic resonance imaging in the diagnosis and follow-up of giant cell
      arteritis: case report and review of literature.
AB  - A female patient with giant cell vasculitis of the abdominal aorta and its
      branches and strongly suspected of having extrapulmonary tuberculosis is
      presented. The diagnoses were based on the clinical picture, laboratory findings,
      and magnetic resonance imaging (MRI) findings. MRI is highly useful in cases
      where echosonography and/or vascular biopsy for histopathological analyses are
      not possible. A combination of giant cell vasculitis and extrapulmonary
      tuberculosis is extremely rare, and therefore, choosing the right treatment
      presents a considerable challenge. MRI performed after 6-month antituberculous
      therapy and 1-year glucocorticoid plus methotrexate therapy showed normal wall of
      the aorta and its branches, which was consistent with clinical and laboratory
      remission. Patients with large vessel vasculitis require regular follow-up by
      MRI.

PMID- 27708946
TI  - Familial aggregation of Crohn's disease and necrotizing sarcoid-like
      granulomatous disease.
AB  - Granulomatous inflammatory diseases are disorders of an undetermined etiology,
      affecting different organs and having a diverse clinical course. Familial
      aggregation of these disorders is being reported increasingly, most commonly
      familial Crohn's disease. We described the coexistence of Crohn's disease and
      necrotizing sarcoid-like granulomatous disease in two siblings from a first
      degree consanguineous Saudi family. The first child presented with recurrent
      abdominal pain associated with bloody stool and arthritis, whereas the second
      child presented with fever of unknown origin and lymphadenopathy as well as
      hepatomegaly without gastrointestinal tract disease. They are phenotypically
      different; however, they share a novel risk locus and allele. This report
      supports the heritability and familial aggregation of granulomatous inflammatory
      diseases and suggests that one causal mutation underlies both Crohn's disease and
      necrotizing sarcoid-like granulomatous disease.

PMID- 27708948
TI  - Churg-Strauss syndrome occurring during omalizumab treatment.

PMID- 27708949
TI  - Differential diagnosis of elevated erythrocyte sedimentation rate and C-reactive
      protein levels: a rheumatology perspective.
AB  - OBJECTIVE: In the case of high erythrocyte sedimentation rate (ESR) and C
      reactive protein (CRP) levels, the diagnosis of the underlying disease can be
      challenging especially in serologically unrevealing patients who have nonspecific
      clinical findings. We aimed to investigate the final distribution of definitive
      diagnoses in patients who initially presented with nonspecific clinical findings
      and sustained elevations in serum ESR/CRP levels. MATERIAL AND METHODS: The
      medical records of patients hospitalized in a rheumatology clinic between January
      2010 and January 2011 were retrospectively analyzed. The patients were classified
      into two main groups: those with previously diagnosed underlying rheumatic
      disease (RD) and those without. The groups were analyzed for the final
      distribution of definitive diagnoses. RESULTS: Out of 112 patients in the general
      study population, 47 had a previous RD and 65 had no previous history of RD. In
      these 65 patients, the most common etiology of nonspecific elevations in ESR/CRP
      levels was new onset RD (52.3%). Polymyalgia rheumatica (PMR) was the most common
      new onset RD (38% of all new onset RD) followed by seronegative rheumatoid
      arthritis. The incidences of infections and malignancies were 24.6% and 9.2%,
      respectively. CRP levels were significantly higher in infections when compared
      with new onset RD or malignancies (p<0.05). In patients with previous RD, the
      flare of the underlying disease was the most common etiology of nonspecific
      elevations in ESR/CRP levels (n=39, 83%, 20 female/19 male). CONCLUSION:
      Extraordinarily high levels of serum CRP in a patient with nonspecific clinical
      findings should raise suspicion for non-rheumatic diagnoses, such as infection
      and malignancy, even in the presence of a previously diagnosed RD. Advanced
      radiological investigation is justified in these cases to rule out malignancy.

PMID- 27708950
TI  - Differential assay reactivity of immunglobulin A anti-beta2 glycoprotein I
      antibodies: implications for the clinical interpretation of antiphospholipid
      antibody testing.
AB  - OBJECTIVE: The routine measurement of IgA anticardiolipin (aCL) and IgA anti
      beta2 glycoprotein I (anti-beta2 GPI) antibodies remain controversial despite
      several studies demonstrating an association with thromboembolic disease in
      patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome
      (APS). This controversy may be a contributing factor for the current under use of
      IgA antiphospholipid antibodies. We aimed to investigate the nature of discrepant
      IgA anti-beta2 GPI reactivity to help define the diagnostic value of IgA
      antiphospholipid antibodies. MATERIAL AND METHODS: Four sera selected from
      SLE/APS patients and positive for antiphospholipid antibodies but having
      discrepant IgA anti-beta2 GPI reactivity on two commercial assays were studied.
      IgA antibodies were affinity purified to investigate anti-beta2 GPI reactivity.
      Column wash through and eluent fractions were tested on both IgA anti-beta2 GPI
      assays. Results were normalized to total protein. Assay conjugates and standards
      from the discrepant assays were interchanged. RESULTS: The diseased samples were
      strongly positive in one assay [144-388 IgA antiphospholipid (APL) units] and
      negative or weakly positive in another assay (9.9-53 APL units). IgA eluents from
      IgA anti-beta2 GPI positive samples reacted 10 times stronger on the reactive
      assay. When normalized to protein content, the eluents showed no cross-reactivity
      for IgG or IgM anti-beta2 GPI antibodies, confirming IgA isotype specificity.
      Conjugate interchange confirmed that both assays bound IgA anti-beta2 GPI
      antibodies, but the anti-IgA conjugate from the reactive assay was 4 times
      stronger, suggesting that its ability to detect IgA anti-beta2 GPI antibodies was
      partially dependent on the anti-IgA conjugate and calibration. CONCLUSION: These
      results confirm not only the presence of IgA anti-beta2 GPI antibodies in the
      selected patient samples but also highlight an IgA conjugate issue for the
      unreactive assay, causing an underestimation of IgA anti-beta2 GPI. This finding
      may assist in the ongoing standardization efforts of APS antibody testing. In
      addition, conclusions from published clinical studies may need to be revised as
      some assays may understate IgA significance.

PMID- 27708951
TI  - Characteristics and outcomes of chronic non-bacterial osteitis in children.
AB  - OBJECTIVE: To determine patient characteristics, clinical presentation, pattern
      of involvement, treatment, and outcome of patients with chronic non-bacterial
      osteitis (CNO). MATERIAL AND METHODS: Consecutive cases of CNO were analyzed at a
      single center for pediatrics and adolescent medicine from 2006 to 2013 in terms
      of patient characteristics, clinical presentation, pattern of involvement,
      treatment, and outcome. RESULTS: We identified 32 children aged 1.5-15 years who
      were diagnosed with CNO between 2006 and 2013. A maximum of 12 bones per patient
      were affected in a total of 114 documented locations. The pelvis and clavicle
      (affecting 34% of patients each) were the most frequently affected bones. The
      foot skeleton was the most commonly affected region in 60% of patients. Skin
      manifestations were found in 7 (21%) patient. Increased inflammatory signs at
      presentation were detected in 18 patients. Pathological findings were found in
      all 30 children examined using magnetic resonance imaging (MRI), in 10 of 11
      children examined using radiography, and in 8 of 10 patients examined using
      skeletal scintigraphy. Bone biopsy was performed in 9 patients. For initial
      treatment, non-steroidal anti-inflammatory drugs (NSAIDs) or coxibs were used in
      28 (87.5%) patients. Remission or satisfactory follow-up was achieved in all
      patients. CONCLUSION: Today, CNO is increasingly diagnosed using MRI and rarely
      through histological examinations. Therapeutic strategies include NSAIDs, which
      are often highly effective. All patients in the present study showed good
      clinical outcomes.

PMID- 27708952
TI  - Rumination modulates stress and other psychological processes in fibromyalgia.
AB  - OBJECTIVE: Fibromyalgia (FM) is characterized by widespread pain and high levels
      of sleep disturbance, fatigue, and altered cognition. Psychological stress can
      modulate these features. In this study, we examined the thinking style of
      rumination in women with FM to assess the effect of rumination on stress levels
      and other psychological variables in FM. MATERIAL AND METHODS: Ninety-eight women
      with FM completed questionnaires to assess levels of rumination, stress, anxiety,
      depression, optimism, control, and coping. T-tests and bivariate (Pearson)
      analysis was performed to assess relationships between rumination and other
      psychological factors. RESULTS: We found that those with higher levels of
      rumination had increased the use of negative coping techniques (p<0.001), higher
      anxiety (p<0.001), depression (p<0.001), and poor sleep levels (p<0.05). Higher
      rumination correlated with lower optimism (p<0.001) and control (Mastery)
      (p<0.001). High rumination correlated strongest with stress (p<0.001). Rumination
      predicted 26% of variance for perceived stress. CONCLUSION: Rumination influenced
      several psychological processes deemed important in FM and was an important
      contributor to stress in FM. Specific interventions targeting rumination in FM
      may improve FM symptoms and outcomes.

PMID- 27708953
TI  - Current antiviral practice and course of Hepatitis B virus infection in
      inflammatory arthritis: a multicentric observational study (A + HBV study).
AB  - OBJECTIVE: The reactivation of hepatitis B virus (HBV) infection is a well-known
      event in hepatitis B surface antigen (HbsAg)-positive patients receiving
      immunosuppressive therapy. The objective of this study was to assess the
      antiviral practice and course of HBV infection in inflammatory arthritis.
      MATERIAL AND METHODS: Nineteen rheumatology centers participated in this
      retrospective study. HbsAg-positive patients who were taking disease-modifying
      antirheumatic drugs and who were being tested for HBV viral load at a minimum of
      two different time points were included. The case report form (CRF) consisted of
      demographic data, rheumatic diseases, treatment profiles, transaminase levels,
      viral hepatitis serological markers, and HBV viral load. The reactivation of HBV
      was defined as the abrupt rise in HBV replication by an increase in serum HBV DNA
      levels in a patient with a previously inactive HBV infection. RESULTS: In total,
      the data of 101 (female 50.5%) patients were included (76 patients with inactive
      HBV carriers and 25 patients with chronic HBV infection). The mean age of
      patients was 44+/-12 years, and the mean follow-up duration was 31+/-22 months.
      Of the 101 patients, 70 (69.3%) received antiviral treatment. HBV reactivation
      was detected in 13 of 76 (17.1%) patients with inactive HBV carriers. HBV
      reactivation was observed less frequently, not although significantly, in those
      patients receiving antiviral prophylaxis compared with those not receiving
      prophylaxis [5/41 (12.2%) vs. 8/33 (24.2%), p=0.17]. Forty-two patients (31
      patients had inactive HBV carriers) were using anti-tumor necrosis factor agents.
      HBV reactivation was detected in 6 of the 31 (19.3%) patients. Twenty-five
      patients had chronic hepatitis, and five (20%) of them had not received antiviral
      prophylaxis. HBV viral loads were persistently elevated in 7 (28%) of 25 patients
      (three patients under and four patients not under antiviral treatment).
      CONCLUSION: HBV reactivation was observed in approximately 17% of patients under
      immunosuppressive treatments. HBV reactivation was more frequently observed in
      those who did not receive antiviral prophylaxis.

PMID- 27708954
TI  - Relapsing polychondritis.
AB  - Relapsing polychondritis (RPC) is a unique and rarely observed autoimmune
      condition regarded as recurrent extensive chondritis of the auricular, nasal, and
      tracheal cartilages. Moreover, heart, main arteries, skin, and eyes may be
      involved. Several forms of clinical manifestations may be seen, and the
      pathogenesis still remains anonymous. A concomitant disease, particularly
      myelodysplasia or other systemic autoimmune disease can be detected in one-third
      of the patients with RPC. The treatment of RPC should be considered on personal
      basis and classified according to disease activity and severity. This study
      reviews the available data on clinical manifestations, pathogenesis, diagnosis,
      and therapeutics of the RPC.

PMID- 27708955
TI  - Dermato-neuro syndrome in a case of scleromyxedema.
AB  - Scleromyxedema is an uncommon connective tissue disease characterized by mucin
      deposits, fibrosis, and proliferation of fibroblasts in the dermis. Although it
      shares similar sclerodermoid features, it is a different clinical entity than
      scleroderma. A monoclonal gammopathy is almost always present; however,
      progression to multiple myeloma is rare. It may have many systemic
      manifestations, of which the most notable being the dermato-neuro syndrome
      because of its rarity and potential fatal outcome. We present a case of a 50-year
      old woman with scleromyxedema in whom the dermato-neuro syndrome developed.

PMID- 27708956
TI  - Therapy resistant idiopathic scleredema: an underlying pathology not always
      present.
AB  - Scleredema is a rare connective tissue disorder of unknown pathogenesis. Three
      types of scleredema have been described, based on its association with
      postinfection, monoclonal gammopathy and diabetes mellitus. We report herein a
      case of scleredema which the diagnosis didn't get specified. The patient was
      followed regularly for 13 years and did not respond to various combinations of
      immunosuppressants and psoralen plus ultraviolet A therapy. Treatment of
      scleredema is quite difficult and of limited success. At present, there is no
      proved treatment for this disease.

PMID- 27708957
TI  - Sjogren's syndrome after silicone breast implantation.
AB  - Sjogren's syndrome, an autoimmune disease characterized by lymphocytic
      infiltration of the lacrimal and salivary glands, leads to dryness of the mouth
      and eyes. Herein, we present a case of Sjogren's syndrome that developed after
      silicone breast implantation. A cause-effect relationship between breast
      implantation and Sjogren's syndrome has not been established. However, the
      possibility of such an association should be considered when a patient with
      silicone implants is admitted to the hospital for treatment of Sjogren's
      syndrome.

PMID- 27708958
TI  - A missed Behcet's case presenting with spontaneous epidural hematoma.
AB  - Spinal vascular events related to Behcet's disease are relatively uncommon. Deep
      vein thrombosis is the most frequent vascular involvement. Anticoagulant therapy
      is a debated issue in Behcet's disease. In this case report, we present a patient
      with a delayed diagnosis of Behcet's disease after development of cervical
      epidural hematoma following anticoagulant therapy due to deep venous thrombosis.
      Anticoagulant therapy without immunosuppressive therapy leading to uncontrolled
      systemic inflammation may be the cause of spinal epidural hematoma. On the other
      hand, epidural vascular involvement as a vasculitic manifestation of Behcet's
      disease in conjunction with anticoagulant therapy may have predisposed to
      spontaneous bleeding via increased fragility or microaneurysms in epidural
      arteries. In this case report, the importance of a multidisciplinary approach to
      Behcet's disease is emphasized.

PMID- 27708959
TI  - Rhabdomyolysis probably induced by influenza vaccine and fibrate therapy.

PMID- 27708960
TI  - Increasing body fat mass reverses bone loss in osteopenia as detected by dual
      energy X-ray absorptiometry scans.
AB  - OBJECTIVE: Low body mass index (BMI) is a known risk factor for osteoporosis and
      is part of the FRAXTM 10-year fracture risk stratification tool for predicting
      fragility fractures. Little is known regarding the effects of changing body
      composition on bone mineral density (BMD). However, increasing fat mass (FM)
      improves BMD in young women with anorexia nervosa. This study aimed to assess
      whether changes in FM over time affected BMD in the general population. MATERIAL
      AND METHODS: Data was collected from patients who underwent dual-energy X-ray
      absorptiometry (DEXA) assessment between 2004 and 2011. Patients were included if
      they had multiple scans, including FM measurements. Our scanners limited these to
      scans of the lumbar spine. Linear regression analysis was performed to identify
      the relationship between changes in FM and BMD. Backwards stepwise linear
      regression analysis was performed to identify confounding factors, including sex,
      risk factors, previous fractures, and baseline BMI. RESULTS: In this study,
      23,239 patients were included, of which 702 met the inclusion criteria. There
      were 609 (86%) females and 93 (13%) males with a mean age of 64.5 (SD 11.2) years
      at first scan. We identified a strong positive correlation between increasing FM
      and BMD between scans (coefficient 28.4; p<0.01; 95% CI, 26.6-30.1). Previous
      pelvic and femur fractures and a history of inflammatory diseases were also
      associated with increasing FM (p<0.05). This relationship was true regardless of
      patients BMI at their first scan. CONCLUSION: These findings suggest that
      patients at high risk of fragility fractures should be encouraged to increase
      their FM as long as they are at a low risk for disease states related to high FM.

PMID- 27708961
TI  - Postural deformities: potential morbidities to cause balance problems in patients
      with ankylosing spondylitis?
AB  - OBJECTIVE: This study aimed to assess the impact of postural deformities caused
      by ankylosing spondylitis (AS) on balance problems. MATERIAL AND METHODS: This
      study included 29 patients with AS and 21 healthy controls. For assessing
      exercise capacity and dynamic balance, timed up and go test, five times sit-to
      stand test, gait speed, and 6-min walk test were performed. Romberg tests were
      used to evaluate static balance and proprioception, whereas Dynamic Gait Index
      (DGI), Functional Gait Assessment (FGA), Berg Balance Scale (BBS), Activity
      Specific Balance Confidence Scale (ABC), Dizziness Handicap Inventory (DHI), and
      functional reach test were used to assess dynamic balance and the risk of
      falling. Using Bath Ankylosing Spondylitis Metrology Index (BASMI) scores,
      patients with AS were divided into two groups: those with scores 0-4 were
      assigned to subgroup AS1, and those with scores 5-10 were assigned to subgroup
      AS2. RESULTS: In the whole group of patients with AS, five times sit-to-stand
      test, tandem Romberg test with eyes closed, and BBS and ABC scores were
      significantly worse than the healthy controls (p<0.05). In the AS2 subgroup
      having more severe and advanced disease, five additional parameters, including
      timed up and go test, 6-min walk test, functional reach test, FGA, and DHI scores
      were also significantly worse than the healthy controls (p<0.05). Comparing the
      two subgroups with each other, only BBS scores were significantly worse in the
      AS2 subgroup than in the AS1 subgroup. CONCLUSION: Although in clinical practice,
      poor balance is not a common problem in AS, possibly because of compensatory
      mechanisms, patients with AS have poorer static and dynamic balance than healthy
      subjects. Significantly worse BBS scores in the AS2 subgroup than in the AS1
      subgroup may suggest the presence of more dynamic balance problems in advanced
      disease; however, future studies comprising larger samples are necessary to
      confirm this assumption.

PMID- 27708962
TI  - Relationship among angiotensin-converting enzyme polymorphism, cardiovascular
      risk, and osteoporotic fractures.
AB  - OBJECTIVE: Angiotensin-converting enzyme (ACE) has been related to cardiovascular
      physiology and bone remodeling. Our aim was to assess the relationship among ACE
      polymorphisms, cardiovascular risk, and osteoporotic fractures. MATERIAL AND
      METHODS: We prospectively enrolled 71 patients with hypertension from 2001 to
      2014. Sociodemographic and medical data were collected. Comorbidity was evaluated
      with Charlson index. Densitometric studies on lumbar spine were performed. ACE
      polymorphism was analyzed by polymerase chain reaction. Data were analyzed using
      SPSS 15.0 (p value <0.05). RESULTS: Homozygous deletion (DD) genotype was
      described in 32.4% of patients, homozygous insertion (II) in 19.7%, and
      heterozygous insertion/deletion (ID) in 47.9%. On stratifying data by ACE
      polymorphism, we observed that DD carriers demonstrated neither greater
      cardiovascular risk factors (30.4% vs. 33.3%, p=0.4) and higher comorbidity
      (34.8% vs. 22.9%, p=0.3) nor higher osteoporotic fracture incidence (17.4% vs.
      16.8%, p=0.9). In women, no significant differences were observed between DD
      homozygous individuals and ID+II subjects. CONCLUSION: It is unclear whether DD
      genotype is an independent risk factor for cardiovascular disease. In contrast to
      our expectations, we found no relationship among the DD genotype, cardiovascular
      risk, and osteoporotic fracture incidence.

PMID- 27708963
TI  - Impact of standard of care treatments and disease variables on outcomes in
      systemic lupus erythematosus trials: analysis from the Lupus Foundation of
      America Collective Data Analysis Initiative.
AB  - OBJECTIVE: Most clinical trials for systemic lupus erythematosus (SLE) study the
      efficacy and safety of investigational agents added to variable background
      immunosuppressants, which has resulted in high response rates in patients treated
      with placebo plus standard of care (SOC) plus rescue measures. This project
      compared the impact of different SOC treatments and disease variables on the
      outcomes of SLE trials. MATERIAL AND METHODS: Data were obtained from 981
      patients receiving only SOC treatments in three nephritis and three general SLE
      trials to compare response and flare rates on the basis of the British Isles
      Lupus Assessment Group (BILAG) index, a measure common to all trials. RESULTS:
      For subjects enrolled in general SLE trials (n=173), those receiving
      mycophenolate mofetil (MMF) had more severe baseline disease, included more
      patients of African descent, and were administered higher baseline steroid doses
      compared with those receiving azathioprine (AZA) or methotrexate (MTX). BILAG
      responses at week 12 were MMF 35%, AZA 49%, MTX 34%, and no immunosuppressant
      (NIS) 65%. At week 52, MMF response rates increased to 41% despite reducing the
      steroid doses, but fell in all others (p=0.07, adjusted for steroids). Patients
      with severe disease activity at baseline (SDAB) who were defined as >=1 BILAG A
      (severe) organ score had lower response rates to AZA or MTX but higher rates to
      MMF or NIS. Interim flares were highest with MMF [flares/patient-year (pt-yr)].
      For all flares, rates were as follows: AZA 1.24, MMF 1.87, MTX 1.42, and NIS 0.81
      and severe flares were as follows: AZA 0.66, MMF 1.29, MTX: 1.20, and NIS 0.55.
      Interim flares occurred in 71% of MMF-endpoint responders, 54% of AZA, 50% of
      MTX, and 22% of NIS. Patients with SDAB had more flares than moderate patients in
      the MMF and MTX groups: MMF: 2.39 vs. 1.03 flares/pt-yr (p=0.01), MTX: 2.33 vs.
      0.63 (p=0.0002), severe flares: 1.87 vs. 0.34 for MMF (p=0.0013), 2.13 vs. 0.40
      for MTX (p<0.0001). In nephritis trials (n=808), MMF subjects received less
      steroids than intravenous cyclophosphamide and response rates were similar, but
      MMF-treated patients had fewer severe flares (p=0.03). CONCLUSION: Compared with
      MMF, AZA and MTX were associated with lower response rates at week 52. AZA
      treated subjects had fewer flares and remained more stable in trials while
      engendering lower placebo plus SOC responses. MMF-treated subjects had frequent
      responses but more flares, suggesting that flares should be included in endpoint
      definitions. Given the likelihood of treatment selection bias, these data do not
      provide conclusions regarding efficacy but may help future trial designs by
      distinguishing factors definable at entry that are predictive of outcomes.

PMID- 27708964
TI  - Oxidative stress and related factors in patients with ankylosing spondylitis.
AB  - OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the
      spine and sacroiliac joints of unknown etiology. Recent studies have reported
      increased oxidative stress, which is implicated in the pathogenesis of a number
      of diseases, in AS. The purpose of this study was to investigate oxidative stress
      and related factors in AS. MATERIAL AND METHODS: Eighty-five patients with AS [36
      (16-64) years; 65 male/20 female] and 56 healthy subjects [36 (21-63) years; 39
      male/17 female] with no known cardiovascular risk factors were enrolled. Serum
      total oxidant status (TOS) and total anti-oxidant status (TAS) were studied. The
      Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis
      disease activity index (BASDAI), and Bath ankylosing spondylitis metrology index
      (BASMI) were calculated. A logistic regression model was used to identify the
      independent risk factors for TOS. RESULTS: No differences were observed in terms
      of demographic characteristics, laboratory findings, or TAS concentrations
      between the patient and control groups. However, the serum TOS levels were
      significantly higher in the AS group than in the controls (p=0.003). The
      comparison of cases of active (BASDAI >=4) and inactive AS revealed significantly
      higher TOS levels in the active disease group. The TOS and TAS concentrations did
      not differ between patients treated with biological agents and those treated with
      conventional agents. Correlation analysis yielded significant correlations
      between TOS and TAS, BASMI, BASFI, BASDAI, erythrocyte sedimentation rate (ESR),
      and high-sensitive C-reactive protein (hs-CRP) (p<0.05; r values ranged from
      0.291 to 0.452) and a positive correlation between TAS and BASMI (p<0.05;
      r=0.344). Based on regression analysis, BASDAI, BASMI, and hs-CRP independently
      predicted the TOS levels [p<0.05, R2: 0.262, and standard error of the estimate
      (SEE): 10.96]. CONCLUSION: Oxidative stress levels were higher in patients with
      AS than in healthy subjects. Patients with active disease status had
      significantly higher oxidative stress than patients with inactive disease status
      and healthy controls. Treatment status has no effect on TOS, and BASMI, BASDAI,
      and hs-CRP are independent variables associated with TOS. The TAS levels were
      found to be associated with only BASMI.

PMID- 27708965
TI  - Viral hepatitis screening guideline before biological drug use in rheumatic
      patients.
AB  - Biological drugs (tumor necrosis factor inhibitors, rituximab, tocilizumab,
      abatacept, and tofacitinib) are important treatment alternatives in rheumatology,
      particularly for resistant patients. However, they may cause hepatitis B virus
      (HBV) and hepatitis C virus (HCV) reactivation; for instance, HBV reactivation
      may occur in a patient who is an inactive hepatitis B surface antigen (HBsAg)
      carrier or who has resolved HBV infection. Therefore, the screening of patients
      before biological treatment and the application of a prophylactic treatment,
      particularly with respect to latent HBV infections, are recommended when
      necessary. This guideline covers pre-treatment screening and follow-up
      recommendations, if required, with respect to viral hepatitides in rheumatology
      patients who are planned to be given biological drugs. Although this guideline is
      prepared for biological disease-modifying antirheumatic drugs (DMARDs), it is
      recommended to be used also for target-oriented DMARDS and medium-high dose
      corticosteroids (>7.5 mg prednisolone/day equivalent). It should be considered
      that the reactivation risk is higher when more than one immunosuppressive drug is
      used.

PMID- 27708966
TI  - Vaccination recommendations for adult patients with rheumatic diseases.
AB  - Infectious diseases in any age group can be successfully prevented through
      immunization. Protection provided through immunization in childhood decreases
      over the years. Immunization in adulthood is important because of the growing
      elderly population, chronic diseases, and globalization. Recommendations on this
      subject are being constantly updated through scientific guidelines. Immunization
      in adulthood is also important in rheumatology. There is an increased risk not
      only of infection in rheumatic diseases but also of infections being more severe.
      Most infections, and their frequently observed complications, are among those
      diseases that can be prevented through immunization. The type of immunization,
      immunosuppressive/immunomodulatory therapy received by the patient, disease
      activity, and presence of chronic diseases affect the immunization process in
      patients with rheumatic diseases. This review will consider the immunization
      process followed in rheumatic diseases and also refer to its application.

PMID- 27708967
TI  - Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia in a patient
      with systemic lupus erythematosus and lupus nephritis.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      several immunological abnormalities. We wish to communicate the case of a patient
      with SLE and lupus nephritis (LN) who developed pseudothrombocytopenia.
      Pseudothrombocytopenia can occur in patients with SLE and LN and should be
      considered when diagnosing patients with thrombocytopenia without bleeding.

PMID- 27708968
TI  - A case of systemic lupus erythematosus with multiple nodules in the bilateral
      lungs and vertebrae.
AB  - We encountered a case of a middle-aged woman with systemic lupus erythematosus.
      As the patient had progressive peripheral neuropathy including foot drop, we
      intended to treat her with intensive immunosuppressive therapy as soon as
      possible. Pretreatment assessment, however, revealed multiple nodular lesions in
      the lungs and bones, suggesting disseminated tumor metastasis or miliary
      tuberculosis. To our surprise, gallium and bone scintigraphy as well as
      cytodiagnosis revealed no sign of malignancy or infection, leading us to suspect
      the presence of another multisystem disorder. The presence of subependymal
      nodules and a periungual fibroma strongly suggested tuberous sclerosis (TS). A
      genetic test revealed a mutation in the TSC1 gene and confirmed the diagnosis.
      Thus, the multiple nodular lesions were most likely a hyperplasia due to TS.
      Although the odds of a comorbidity of more than one multisystem disorder are
      considered to be quite low, it should be kept in mind that when such a situation
      does exist, the comorbidity may make the presenting symptoms extremely diverse.

PMID- 27708969
TI  - Rheumatoid arthritis and tabetic arthropathy: physiopathological link or simple
      association?
AB  - To the best of our knowledge, the association of rheumatoid arthritis and tabetic
      arthropathy has never been described before in the literature. We report here a
      first observation. We report the case of a 50-year-old man, treated for
      syphilitic arthritis evolving for 4 years, who presented with a table of
      rheumatoid arthritis. The diagnosis of rheumatoid arthritis was established
      according to the 2010 American College of Rheumatology/European League Against
      Rheumatism criteria (ACR/EULAR). The treatment was based on weekly injection of
      methotrexate and a symptomatic treatment by corticosteroid. The association of
      rheumatoid arthritis and tabetic arthropathy is rare, to our knowledge this is
      the first case reported. This case reminds us that a neuropathic arthropathy as
      tabetic arthropathy, although it is rare, can be associated in a sporadic or
      exceptional way with other rheumatic disease like rheumatoid arthritis. A
      physiopathological link between the both diseases remains to be proved.

PMID- 27708970
TI  - Potential protein targets of the peptidylarginine deiminase 2 and
      peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its
      possible meaning.
AB  - OBJECTIVE: The molecular mechanism of citrullination involves the calcium
      dependent peptidylarginine deiminase (PAD) family of enzymes. These enzymes
      induce a stereochemical modification of normal proteins and transform them into
      autoantigens, which in rheumatoid arthritis trigger a complex cascade of joint
      inflammatory events followed by chronic synovitis, pannus formation, and finally,
      cartilage destruction. By hypothesizing that PAD2 and PAD4 enzymes produce
      autoantigens, we investigated five possible synovial protein targets of PAD
      enzymes. MATERIAL AND METHODS: We measured PAD2, PAD4, and citrullinated proteins
      in 10 rheumatoid and 10 osteoarthritis synovial biopsies and then assessed the
      post-translational modifications of fibrinogen, cytokeratin, tubulin, IgG, and
      vimentin proteins using a double-fluorescence assay with specific antibodies and
      an affinity-purified anti-citrullinated peptide (CCP) antibody. The degree of co
      localization was analyzed, and statistical significance was determined by ANOVA,
      Fisher's exact test, and regression analysis. RESULTS: The principal results of
      this study demonstrated that citrullinated proteins, such as fibrinogen, IgG, and
      other probed proteins, were targets of PAD2 and PAD4 activity in rheumatoid
      synovial biopsies, whereas osteoarthritis biopsies were negative for this enzyme
      (p<0.0001). An analysis of citrullination sites using the UniProtKB/Swiss-Prot
      data bank predicts that the secondary structure of the analyzed proteins displays
      most of the sites for citrullination; a discussion regarding its possible meaning
      in terms of pathogenesis is made. CONCLUSION: Our results support the conclusion
      that the synovial citrullination of proteins is PAD2 and PAD4 dependent.
      Furthermore, there is a collection of candidate proteins that can be
      citrullinated.

PMID- 27708971
TI  - Low vitamin D status in systemic sclerosis and the impact on disease phenotype.
AB  - OBJECTIVE: Vitamin D has pleiotropic effects including immunomodulatory,
      cardioprotective, and antifibrotic properties and is thus able to modulate the
      three main links in scleroderma pathogenesis. The aim of the study was to
      evaluate the level of vitamin D in patients with systemic sclerosis and to
      analyze the associations between the concentration of vitamin D and the features
      of systemic sclerosis. MATERIAL AND METHODS: Fifty-one consecutive patients were
      evaluated for visceral involvement, immunological profile, activity, severity
      scores, and quality of life. The vitamin D status was evaluated by measuring the
      25hydroxy-hydroxyvitamin D serum levels. RESULTS: The mean vitamin D level was
      17.06+/-9.13 ng/dL. Only 9.8% of the patients had optimal vitamin D levels;
      66.66% of them had insufficient 25(OH)D levels, while 23.52% had deficient
      levels. No correlation was found between vitamin D concentration and age, sex,
      autoantibody profile, extent of skin involvement, or vitamin D supplementation.
      Vitamin D levels were correlated with the diffusing capacity of the lung for
      carbon monoxide (p=0.019, r=0.353), diastolic dysfunction (p=0.033, r=-0.318),
      digital contractures (p=0.036, r=-0.298), and muscle weakness (p=0.015, r=-0.377)
      and had a trend for negative correlation with pulmonary hypertension (p=0.053, r=
      0.29). CONCLUSION: Low levels of vitamin D are very common in systemic sclerosis.
      Poor vitamin status seems to be related with a more aggressive disease with
      multivisceral and severe organ involvement, especially pulmonary and cardiac
      involvement.

PMID- 27708972
TI  - Surgery for lumbar spinal stenosis in patients with rheumatoid arthritis: A
      multicenter observational study.
AB  - OBJECTIVE: To compare clinical outcomes following microdecompression surgery or
      laminectomy for central lumbar spinal stenosis (LSS) between patients with
      rheumatoid arthritis (RA) and patients without rheumatic disease. MATERIAL AND
      METHODS: Data were collected from the Norwegian Registry for Spine Surgery. The
      primary outcome was change in the Oswestry Disability Index (ODI) score at 1
      year. The secondary endpoints were health-related quality of life that was
      measured using the Euro-Qol-5D (EQ-5D), back pain numerical rating scale (NRS),
      leg pain NRS, and complications. RESULTS: A total of 1433 patients were included
      (1396 controls and 37 patients with RA). For all the patients, there was an
      improvement in ODI score 16.7 points; 95% confidence interval (CI), 15.7, 17.7;
      p<0.001). There were no differences between controls and patients with RA with
      respect to the mean changes of ODI scores (-2.5 points; 95% CI, -9.0 to 4.1;
      p=0.462), EQ-5D (p=0.295), back pain NRS (p=0.194), leg pain NRS (p=0.927), and
      complications within 3 months of surgery (12.8% vs. 13.5%, p=0.806). At 1 year,
      68.6% (n=775) of controls had achieved a minimal clinically important difference
      (>=8 points ODI score improvement) compared with 65.5% (n=19) of patients with RA
      (p=0.726). CONCLUSION: Patients with RA experienced similar and large
      improvements in patient-reported outcomes following surgical decompression for
      LSS compared with patients without rheumatic disease. There was no increased risk
      of complications in patients with RA.

PMID- 27708973
TI  - Relationship between endothelial dysfunction and microalbuminuria in familial
      Mediterranean fever.
AB  - OBJECTIVE: The aim of our study is to investigate the relationship between
      microalbuminuria and flow-mediated dilatation in familial Mediterranean fever
      (FMF) patients. MATERIAL AND METHODS: In our study, there were two groups
      consisting of 54 patients who were out of the attack period (43 of whom had no
      microalbuminuria and 11 of whom had microalbuminuria) and 40 healthy controls
      (M/F: 12/28). RESULTS: There was no statistically difference between patient and
      control groups'age (25.06+/-8.07, 22.89+/-6.00 years, respectively). Flow
      mediated dilatation (FMD) percentages were significantly different between the
      three groups (p=0.01). It was observed that there was a correlation between
      microalbuminuria and FMD percentage. CONCLUSION: Endothelial dysfunction and
      renal damage occurred as a result of low-grade chronic inflammation.
      Microalbuminuria, which is the indicator of renal damage and endothelial
      dysfunction, and FMD show that endothelial functions can be used in the following
      of early detection of renal damage and endothelial functions in FMF patients.

PMID- 27708975
TI  - Janus kinase 2 V617F mutation and thrombotic events in Behcet's disease: The
      Alexandria experience.

PMID- 27708974
TI  - Evaluating disease activity in patients with ankylosing spondylitis and
      rheumatoid arthritis using 99mtc-glucosamine.
AB  - OBJECTIVE: To evaluate the clinical utility of a novel radiotracer, 99mTc
      glucosamine, in assessing disease activity of both rheumatoid arthritis (RA) and
      ankylosing spondylitis (AS). Material and Methods: Twenty-five patients with RA
      (nine males and 16 females) and 12 patients with AS (all male) at various stages
      of disease were recruited for the study. A clinical history and examination was
      performed, followed by the measurement of hematological, biochemical, and
      autoimmune serological parameters to assess disease activity. 99mTc-glucosamine
      was intravenously administered and scans were compared with other imaging
      modalities, including plain X-ray, magnetic resonance imaging (MRI), and bone
      scans. RESULTS: In patients with AS, 99mTc-glucosamine scans were more capable of
      identifying active disease and differentiating between inflammatory and non
      inflammatory causes. In patients with RA, 99mTc-glucosamine accumulated at all
      known sites of disease involvement. Uptake was most pronounced in patients with
      active untreated disease. The relative tracer activity in the involved joints
      increased with time compared with that in the adjoining soft tissue, liver, and
      cardiac blood pool. Using Spearman's correlation coefficient, there was a
      positive correlation among glucosamine scan scores, C-reactive protein (p=0.048),
      and clinical assessment (p=0.003), which was not noted with bone scans.
      CONCLUSION: The radiotracer was well tolerated by all patients, with no adverse
      reactions. 99mTc-glucosamine imaging could detect spinal inflammation in AS. With
      respect to RA, 99mTc-glucosamine was a viable alternative to 99mTc-labeled
      methylene diphosphonate nuclear bone scans for imaging inflamed joints and had
      the added advantage of demonstrating a significant clinical correlation between
      disease activity and scan findings.

PMID- 27708977
TI  - Kaposi's sarcoma concurrent with granulomatosis polyangiitis.
AB  - Kaposi's sarcoma (KS), a malignant vascular tumor, can develop in patients who
      receive corticosteroids or immunosuppressive therapy. We report a patient with KS
      and granulomatosis polyangiitis (GPA). To the best of our knowledge, this is the
      first report regarding the co-occurrence of these two diseases. The physician
      must be aware of the risk of cancer in patients with rheumatism.

PMID- 27708978
TI  - Teriparatide for the rapid resolution of delayed healing of atypical fractures
      associated with long-term bisphosphonate use.
AB  - Bisphosphonates (BPs) are the most widely used drugs to treat osteoporosis.
      However, recent reports associated to long-term BPs use with atypical low-impact
      fractures and prodromal pain. It is estimated that 26% of the cases of atypical
      fractures associated with the long-term use of BPs show delayed healing or
      nonunion. Teriparatide [PTH1-34] (TPTD) is an anabolic drug shown to be effective
      in stimulating bone formation. The aim was to describe the course of a right
      diaphyseal femoral fracture sustained by a patient on long-term BPs treatment. A
      57-year-old postmenopausal Caucasian female presented with delayed healing of a
      right femoral diaphyseal fracture 10 months after the fracture, despite having
      received orthopedic treatment. The fracture was preceded by progressive, severe,
      and bilateral thigh pain. Her medical history included osteopenia that was
      treated with alendronate over 7 years. On presentation at our clinic, the patient
      ambulated with the aid of a walking cane. The diagnosis was an atypical right
      femoral fracture associated with long-term alendronate use. The levels of the
      following parameters were measured: mineral metabolism laboratory: intact
      parathormone, 40 ng/mL (reference values (rv): 10-65 ng/mL); 25-hydroxyvitamin D,
      40 ng/mL (rv: >30 ng/mL); serum Crosslaps, 318 ng/mL (rv: 80-590 ng/mL); and bone
      specific alkaline phosphatase, 76UI/L (rv: 31-95UI/L)]. Magnetic resonance
      imaging of the left femur was performed, which revealed a diaphyseal stress
      fracture. She was prescribed 20 MUg/day of subcutaneous (s.c.) TPTD (PTH1-34,
      Forteo; Eli Lilly Co., Indianapolis, IN, United States). A computed tomography
      scan performed 3 months later showed that the fracture had healed; the patient
      was able to resume her usual activities. Twenty micrograms per day of s.c. TPD
      accelerated the healing of the atypical fracture associated with long-term
      alendronate therapy, allowing a fast recovery of ambulation and quality of life.

PMID- 27708979
TI  - Hydroxychloroquine-induced agranulocytosis in a patient with long-term rheumatoid
      arthritis.
AB  - Agranulocytosis is a rare and little-known side effect of hydroxychloroquine use.
      This report describes the case of a 71-year-old woman with poorly controlled
      rheumatoid arthritis who developed agranulocytosis after several months of
      hydroxychloroquine therapy. She had been on several different disease-modifying
      antirheumatic drugs, including methotrexate and leflunomide, for her rheumatoid
      arthritis. Treatment became complicated following a diagnosis of leflunomide
      induced pulmonary fibrosis that was discovered after an intensive care unit (ICU)
      admission for severe Pseudomonas pneumonia. All treatment was stopped apart from
      steroids and hydroxychloroquine. Because of persistent disabling symptoms,
      rituximab infusions were given, which improved the disease control. A second
      admission occurred after a routine blood test revealed agranulocytosis.
      Hydroxychloroquine was stopped, and after 24 h, she was discharged home. Blood
      counts returned to normal within 2 weeks of hydroxychloroquine cessation; hence,
      after the review of investigations, a diagnosis of hydroxychloroquine-induced
      agranulocytosis was made. This report considers current literature on
      hydroxychloroquine-induced agranulocytosis and explores the potential causes for
      this occurrence.

PMID- 27708976
TI  - The clinical significance of antiphospholipid antibodies in systemic lupus
      erythematosus.
AB  - Antiphospholipid syndrome (APS) is the association of thrombosis and/or pregnancy
      morbidity with antiphospholipid antibodies (aPL). Thirty to forty percent of
      systemic lupus erythematosus (SLE) patients are tested positive for aPL, which
      may have an impact on the SLE presentation, management, and prognosis. Compared
      with SLE patients without aPL, those with aPL have a higher prevalence of
      thrombosis, pregnancy morbidity, valve disease, pulmonary hypertension, livedo
      reticularis, thrombocytopenia, hemolytic anemia, acute/chronic renal vascular
      lesions, and moderate/severe cognitive impairment; worse quality of life; and
      higher risk of organ damage. The use of low-dose aspirin (LDA) is controversial
      for primary thrombosis and pregnancy morbidity prevention because of the lack of
      strong prospective controlled data. Similarly, the use of anticoagulation is
      controversial for patients with an aPL-related nephropathy. Until further studies
      are available, physicians should discuss the risk/benefits of LDA or
      anticoagulation as well as the available literature with patients.

PMID- 27708980
TI  - Tuberculous sacroiliitis: A cause of bone marrow edema in magnetic resonance
      imaging.

PMID- 27708981
TI  - Pregnancy Complicated by Gorham-Stout Disease and Refractory Chylothorax.
AB  - Introduction Gorham-Stout Disease (GSD) is a rare disorder of bony destruction
      due to lymphangiomatosis, and is often triggered by hormones. One complication of
      GSD is the development of chylothorax, which carries a high mortality rate. Very
      little experience has been published to guide management in GSD during pregnancy
      to optimize both fetal and maternal health. Case Study A 20-year-old woman with
      known GSD presented with shortness of breath at 18 weeks of pregnancy, due to
      bilateral chylothoraces which required daily drainage. To minimize chylous fluid
      formation, she was placed on bowel rest with total parenteral nutrition (limiting
      lipid intake) and received octreotide to decrease splanchnic blood flow and
      chylous fluid drainage. Treatment options were limited due to her pregnancy.
      Twice daily home chest tube drainage of a single lung cavity, total parenteral
      nutrition, octreotide, and albumin infusions allowed successful delivery of a
      healthy 37 weeks' gestation infant by cesarean delivery. Discussion This case
      illustrates the management of a rare clinical disease of bone resorption and
      lymphangiomatosis complicated by bilateral, refractory chylothoraces, triggered
      by pregnancy, in whom treatment options are limited, and the need for a
      multidisciplinary health care team to ensure successful maternal and fetal
      outcomes.

PMID- 27708983
TI  - Overuse Cervical Dystonia: A Case Report and Literature Review.
AB  - BACKGROUND: Overuse or task-specific dystonia has been described in a number of
      professions characterized by repetitive actions, typically affecting the upper
      extremities. Cervical dystonia (CD), however, has rarely been associated with
      overuse. CASE REPORT: We present a case report of typical CD that developed in
      the context of chronic repetitive movements associated with the patient's
      professional occupation as an office manager who spent many hours per day holding
      a phone to his ear. DISCUSSION: Overuse CD should be suspected when typical
      symptoms and signs of CD develop in the context of chronic repetitive use or
      overuse of cervical muscles, especially where exacerbating tasks involve
      asymmetric postures.

PMID- 27708984
TI  - Purkinje Cell Cytoplasmic Antibody (PCA-2)-related Chorea-Dystonia Syndrome.

PMID- 27708982
TI  - Post-hypoxic Myoclonus: Current Concepts, Neurophysiology, and Treatment.
AB  - BACKGROUND: Myoclonus may occur after hypoxia. In 1963, Lance and Adams described
      persistent myoclonus with other features after hypoxia. However, myoclonus
      occurring immediately after hypoxia may demonstrate different syndromic features
      from classic Lance-Adams syndrome (LAS). The aim of this review is to provide up
      to-date information about the spectrum of myoclonus occurring after hypoxia with
      emphasis on neurophysiological features. METHODS: A literature search was
      performed on PubMed database from 1960 to 2015. The following search terms were
      used: "myoclonus," "post anoxic myoclonus," "post hypoxic myoclonus," and "Lance
      Adams syndrome." The articles describing clinical features, neurophysiology,
      management, and prognosis of post-hypoxic myoclonus cases were included for
      review. RESULTS: Several reports in the literature were separated clinically into
      "acute post-hypoxic myoclonus," which occurred within hours of severe hypoxia,
      and "chronic post-hypoxic myoclonus," which occurred with some recovery of mental
      status as the LAS. Acute post-hypoxic myoclonus was generalized in the setting of
      coma. Chronic post-hypoxic myoclonus presented as multifocal cortical action
      myoclonus that was significantly disabling. There was overlap of
      neurophysiological findings for these two syndromes but also different features.
      Treatment options for these two distinct clinical-neurophysiologic post-hypoxic
      myoclonus syndromes were approached differently. DISCUSSION: The review of
      clinical and neurophysiological findings suggests that myoclonus after hypoxia
      manifests in one or a combination of distinct syndromes: acute and/or chronic
      myoclonus. The mechanism of post-hypoxic myoclonus may arise either from cortical
      and/or subcortical structures. More research is needed to clarify mechanisms and
      treatment of post-hypoxic myoclonus.

PMID- 27708985
TI  - Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary
      Tuberculosis Patients in South India.
AB  - OBJECTIVES: To examine demographics, clinical correlates, sputum AFB (acid fast
      bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and
      drug resistance in a cohort of newly-diagnosed, smear positive pulmonary
      tuberculosis (TB) patients with respect to HIV status at baseline, and compare
      smear conversion rates, side effects and mortality after two months. DESIGN: A
      prospective study among 54 HIV positive and 41 HIV negative pulmonary TB
      patients. Data were collected via face-to-face interviews, review of medical
      records, and lab tests. RESULTS: HIVTB co-infected patients, though more
      symptomatic at baseline, showed more improvement in their symptoms compared to
      HIV-uninfected TB patients at follow-up. The HIV co-infected group had more
      prevalent perceived side effects, and sputum smear positivity was marginally
      higher compared to the HIV negative group at follow-up. Mortality was higher
      among the HIV-infected group. Both groups had high rates of resistance to first
      line anti-tubercular drugs, particularly isoniazid. There was no significant
      difference in the drug resistance patterns between the groups. CONCLUSIONS:
      Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular
      treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently
      needed in India. As resistance to ART and/or ATT is directly linked to medication
      non-adherence, the use of counseling, regular reinforcement, early detection and
      appropriate intervention strategies to tackle this complex issue could help
      prevent premature mortality and development of resistance in HIV-TB co-infected
      patients. The high rate of isoniazid resistance might preclude its use in India
      as prophylaxis for latent TB in HIV infected persons as per the World Health
      Organization (WHO) guideline.

PMID- 27708986
TI  - Changes in peripheral blood lymphocytes in polycythemia vera and essential
      thrombocythemia patients treated with pegylated-interferon alpha and correlation
      with JAK2V617F allelic burden.
AB  - BACKGROUND: Pegylated-interferon alpha (PegINFalpha) treatment of patients with
      polycythemia vera (PV) and essential thrombocythemia (ET) has resulted in long
      term clinical response, decreased JAK2V617F allelic burden and restoration of
      polyclonal hematopoiesis. The mechanisms of the beneficial effects of PegINFalpha
      are not clear, but available evidence suggests direct suppression of JAK2-mutated
      clone, induction of dormant stem cells to proliferation, and augmentation of an
      immune effect against PV and ET clones. METHODS: We analyzed the phenotype and
      frequency of peripheral blood lymphocytes (PBL) from PegINFalpha treated patients
      and compared them to patients treated with hydroxyurea (HU). Samples collected at
      various time points before and during treatment were analyzed using multicolor
      flow cytometry. RESULTS: We found that PegINFalpha increased the frequency of
      peripheral blood CD4+ Foxp3+ regulatory T cells (Treg). Highly suppressive Treg,
      characterized by co-expression of CD39 and HLA-DR, were also increased in PBL
      from PegINFalpha treated patients. We observed an augmentation of cycling CD8+ T
      cells, NK cells, and of poorly activated CD38+CD8+ T cells. Our results also
      suggest that PegINFalpha increased the frequency of PD-1+ CD4+ helper cells and
      PD-1+ CD4+ Foxp3+ Treg cells. None of these changes were present in HU treated
      patients. We analyzed the correlation between changes in different T cell
      populations in the peripheral blood with the changes in JAK2V617F allelic burden
      in clonal granulocytes. Augmentation of Ki-67+ Treg, HLA-DR+ CD39+ Treg, Helios+
      Treg and HLA-DR+ CD38+ CD8+ T cells correlated with an increase in JAK2V617F
      allelic burden. We also found a positive correlation between PD-1+ Treg and
      JAK2V617F allelic burden; however, the number of available patients was small (n
      = 7). CONCLUSIONS: We report marked changes in frequencies of PBL subsets after
      PegINFalpha treatment, suggesting an immunomodulatory effect by PegINFalpha.
      Generation of a more suppressive immune response, as measured by an increase in
      highly suppressive Treg and poorly activated CD8+ T cells, correlated with a poor
      molecular response. In this study, we have not identified changes in the PBL that
      would indicate the presence of an effective anti-tumor response.Trial
      registration NCT01259856, December 7. 2010 and NCT01259817, December 6. 2010,
      Grant #1P01CA108671-O1A2, July 17. 2006, Sponsor: MPDRC/NIH, NCI-2012-00269,
      January 12. 2011 and NCI-2012-00268, January 12. 2011.

PMID- 27708987
TI  - Comparative Study of Epidemiological and Anthropological Aspects of Diabetes and
      Hypertension in Cameroon.
AB  - The traditional medicine in Africa in general and specifically in Cameroon does
      not manage diabetes and arterial hypertension very well. Yet, these pathologies
      are becoming more prevalent among the populations that need adequate knowledge to
      fight against them. Therefore the present study was designed to determine the
      knowledge, attitudes and practices of indigenous people regarding diabetes and
      hypertension control, and to assess the epidemiological aspects of these diseases
      in order to reinforce their health education and promote a better health care
      through traditional medicine. To achieve this objective, 1,131 households
      including 70 traditional healers, 114 diabetics, 167 hypertensive patients, 30
      hypertensive patients-diabetics and other Cameroonians were questioned on their
      ethnomedical knowledge of diabetes and arterial hypertension. Fifty-eight
      randomly distributed tribes were taking in account. The elucidation of
      anthropological and epidemiological aspects of diabetes and hypertension improved
      the beliefs of indigenous people and facilitated the modernization of diabetes
      and hypertension comprehension that remained focused on the elucidation of
      diseases' causes and complications, as well as on the behaviors that could help
      translate biomedical terms into locally meaningful metaphors.

PMID- 27708988
TI  - Large increase in dissolved inorganic carbon flux from the Mississippi River to
      Gulf of Mexico due to climatic and anthropogenic changes over the 21st century.
AB  - It is recognized that anthropogenic factors have had a major impact on carbon
      fluxes from land to the ocean during the past two centuries. However, little is
      known about how future changes in climate, atmospheric CO2, and land use may
      affect riverine carbon fluxes over the 21st century. Using a coupled hydrological
      biogeochemical model, the Dynamic Land Ecosystem Model, this study examines
      potential changes in dissolved inorganic carbon (DIC) export from the Mississippi
      River basin to the Gulf of Mexico during 2010-2099 attributable to climate
      related conditions (temperature and precipitation), atmospheric CO2, and land use
      change. Rates of annual DIC export are projected to increase by 65% under the
      high emission scenario (A2) and 35% under the low emission scenario (B1) between
      the 2000s and the 2090s. Climate-related changes along with rising atmospheric
      CO2 together would account for over 90% of the total increase in DIC export
      throughout the 21st century. The predicted increase in DIC export from the
      Mississippi River basin would alter chemistry of the coastal ocean unless
      appropriate climate mitigation actions are taken in the near future.

PMID- 27708989
TI  - Revising the slant column density retrieval of nitrogen dioxide observed by the
      Ozone Monitoring Instrument.
AB  - Nitrogen dioxide retrievals from the Aura/Ozone Monitoring Instrument (OMI) have
      been used extensively over the past decade, particularly in the study of
      tropospheric air quality. Recent comparisons of OMI NO2 with independent data
      sets and models suggested that the OMI values of slant column density (SCD) and
      stratospheric vertical column density (VCD) in both the NASA OMNO2 and Royal
      Netherlands Meteorological Institute DOMINO products are too large, by around 10
      40%. We describe a substantially revised spectral fitting algorithm, optimized
      for the OMI visible light spectrometer channel. The most important changes
      comprise a flexible adjustment of the instrumental wavelength shifts combined
      with iterative removal of the ring spectral features; the multistep removal of
      instrumental noise; iterative, sequential estimates of SCDs of the trace gases in
      the 402-465 nm range. These changes reduce OMI SCD(NO2) by 10-35%, bringing them
      much closer to SCDs retrieved from independent measurements and models. The
      revised SCDs, submitted to the stratosphere-troposphere separation algorithm,
      give tropospheric VCDs ~10-15% smaller in polluted regions, and up to ~30%
      smaller in unpolluted areas. Although the revised algorithm has been optimized
      specifically for the OMI NO2 retrieval, our approach could be more broadly
      applicable.

PMID- 27708990
TI  - MODIS comparisons with northeastern Pacific in situ stratocumulus microphysics.
AB  - Vertical sounding measurements within stratocumuli during two aircraft field
      campaigns, Marine Stratus/stratocumulus Experiment (MASE) and Physics of
      Stratocumulus Top (POST), are used to validate Moderate Resolution Imaging
      Spectroradiometer (MODIS) cloud optical thickness (COT), cloud liquid water path
      (LWP), and cloud effective radius (re). In situ COT, LWP, and re were calculated
      using 5 m vertically averaged droplet probe measurements of complete vertical
      cloud penetrations. MODIS COT, LWP, and re 1 km pixels were averaged along these
      penetrations. COT comparisons in POST showed strong correlations and a near 1:1
      relationship. In MASE, comparisons showed strong correlations; however, MODIS COT
      exceeded in situ COT, likely due to larger temporal differences between MODIS and
      in situ measurements. LWP comparisons between two cloud probes show good
      agreement for POST but not MASE, giving confidence to POST data. Both projects
      provided strong LWP correlations but MODIS exceeded in situ by 14-36%. MODIS in
      situ re correlations were strong, but MODIS 2.1 um re exceeded in situ re, which
      contributed to LWP bias; in POST, MODIS re was 20-30% greater than in situ re.
      Maximum in situ re near cloud top showed comparisons nearer 1:1. Other MODIS re
      bands (3.7 um and 1.6 um) showed similar comparisons. Temporal differences
      between MODIS and in situ measurements, airplane speed differences, and cloud
      probe artifacts were likely causes of weaker MASE correlations. POST COT
      comparison was best for temporal differences under 20 min. POST data validate
      MODIS COT but it also implies a positive MODIS re bias that propagates to LWP
      while still capturing variability.

PMID- 27708991
TI  - Using a multiwavelength suite of microwave instruments to investigate the
      microphysical structure of deep convective cores.
AB  - Due to the large natural variability of its microphysical properties, the
      characterization of solid precipitation is a longstanding problem. Since in situ
      observations are unavailable in severe convective systems, innovative remote
      sensing retrievals are needed to extend our understanding of such systems. This
      study presents a novel technique able to retrieve the density, mass, and
      effective diameter of graupel and hail in severe convection through the
      combination of airborne microwave remote sensing instruments. The retrieval is
      applied to measure solid precipitation properties within two convective cells
      observed on 23-24 May 2014 over North Carolina during the IPHEx campaign by the
      NASA ER-2 instrument suite. Between 30 and 40 degrees of freedom of signal are
      associated with the measurements, which is insufficient to provide full
      microphysics profiling. The measurements have the largest impact on the retrieval
      of ice particle sizes, followed by ice water contents. Ice densities are mainly
      driven by a priori assumptions, though low relative errors in ice densities
      suggest that in extensive regions of the convective system, only particles with
      densities larger than 0.4 g/cm3 are compatible with the observations. This is in
      agreement with reports of large hail on the ground and with hydrometeor
      classification derived from ground-based polarimetric radars observations. This
      work confirms that multiple scattering generated by large ice hydrometeors in
      deep convection is relevant for airborne radar systems already at Ku band. A
      fortiori, multiple scattering will play a pivotal role in such conditions also
      for Ku band spaceborne radars (e.g., the GPM Dual Precipitation Radar).

PMID- 27708992
TI  - Surface mass balance contributions to acceleration of Antarctic ice mass loss
      during 2003-2013.
AB  - Recent observations from satellite gravimetry (the Gravity Recovery and Climate
      Experiment (GRACE) mission) suggest an acceleration of ice mass loss from the
      Antarctic Ice Sheet (AIS). The contribution of surface mass balance changes (due
      to variable precipitation) is compared with GRACE-derived mass loss acceleration
      by assessing the estimated contribution of snow mass from meteorological
      reanalysis data. We find that over much of the continent, the acceleration can be
      explained by precipitation anomalies. However, on the Antarctic Peninsula and
      other parts of West Antarctica, mass changes are not explained by precipitation
      and are likely associated with ice discharge rate increases. The total apparent
      GRACE acceleration over all of the AIS between 2003 and 2013 is -13.6 +/- 7.2
      Gt/yr2. Of this total, we find that the surface mass balance component is -8.2 +/
      2.0 Gt/yr2. However, the GRACE estimate appears to contain errors arising from
      the atmospheric pressure fields used to remove air mass effects. The estimated
      acceleration error from this effect is about 9.8 +/- 5.8 Gt/yr2. Correcting for
      this yields an ice discharge acceleration of -15.1 +/- 6.5 Gt/yr2.

PMID- 27708993
TI  - The Dst index underestimates the solar cycle variation of geomagnetic activity.
AB  - It is known that the correction of the Kyoto Dst index for the secular variation
      of the Earth's internal field produces a discontinuity in the Kyoto Dst index at
      the end of each year. We show that this secular correction also introduces a
      significant baseline error to the Kyoto Dst index that leads to an underestimate
      of the solar cycle variation of geomagnetic activity and of the strength of the
      ring current as measured by the Kyoto Dst index. Thus, the average value of the
      Kyoto Dst index would be approximately 13 nT more negative for the active year
      2003 compared to quiet years 2006 and 2009 if the Kyoto Dst index properly
      measured the effects of the ring current and other currents that influence the
      Dst observatories. Discontinuities in the Kyoto Dst index at the end of each year
      have an average value of about 5 nT, but the discontinuity at the end of year
      2002 was approximately 12 nT, and the discontinuity at the end of year 1982 may
      have been as large as 20 nT.

PMID- 27708994
TI  - Densely Packed Microgoblet Laser Pairs for Cross-Referenced Biomolecular
      Detection.
AB  - Microgoblet laser pairs are presented for cross-referenced on-chip biomolecular
      sensing. Parallel readout of the micro-lasers facilitates effective mutual
      filtering of highly localized refractive index and temperature fluctuations in
      the analyte. Cross-referenced detection of two different types of proteins and
      complete chemical transducer reconfiguration is demonstrated. Selective surface
      functionalization of the individual lasers with high spatial accuracy is achieved
      by aligned microcontact stamping.

PMID- 27708995
TI  - Virus-Surface-Mimicking Surface Clustering of AuNPs onto DNA-Entrapped Polymeric
      Nanoparticle for Enhanced Cellular Internalization and Nanocluster-Induced NIR
      Photothermal Therapy.
AB  - Virus-surface-mimicking decoration of deoxyribonucleic acid (DNA)-entrapped
      polymeric nanoparticle with AuNPs is demonstrated to lead to enhanced cellular
      uptake, improved gene transfection, and particularly efficient near-infrared
      photothermal therapy that cannot be achieved by both of them separately. This
      hybrid nanosystem represents a novel paradigm of multipurpose organic-inorganic
      nanoplatform, especially for cancer treatments.

PMID- 27708996
TI  - Reserving Interior Void Space for Volume Change Accommodation: An Example of
      Cable-Like MWNTs@SnO2@C Composite for Superior Lithium and Sodium Storage.
AB  - Reserving interior void space in the cable-like structure of multiwalled carbon
      nanotubes-in-SnO2-in-carbon layer (MWNTs@SnO2@C) is reported for the first time.
      Such a design enables the structure performing excellent for Li and Na storage,
      which benefit from the good electrical conductivity of MWNTs and carbon layer as
      well as the reserved void space to accommodate the volume changes of SnO2.

PMID- 27708998
TI  - Understanding Inhomogeneous Reactions in Li-Ion Batteries: Operando Synchrotron X
      Ray Diffraction on Two-Layer Electrodes.
AB  - To understand inhomogeneous reactions perpendicular to the current collector in
      an electrode for batteries, a method combining operando synchrotron X-ray
      diffraction and two-layer electrodes with different porosities is developed. The
      two layers are built using two different active materials (LiNi0.80Co0.15Al0.05O2
      and LiMn2O4), therefore, tracing each diffraction pattern reveals which active
      material is reacting during the electrochemical measurement in transmission mode.
      The results demonstrate that the active material close to the separator is
      obviously more active than that one close to the current collector in the case of
      low porosity electrodes. This inhomogeneity should be due to the rate-limitation
      and especially to low average ionic conductivity of the electrolyte in the porous
      electrode because the current flows first mainly into the electrode regions close
      to the separator. The inhomogeneity is found to be mitigated by the adjustment of
      the electrode density and thus porosity. Hence, the novel operando method reveals
      a clear inhomogeneous reaction perpendicular to the current collector.

PMID- 27708997
TI  - Phases Hybriding and Hierarchical Structuring of Mesoporous TiO2 Nanowire Bundles
      for High-Rate and High-Capacity Lithium Batteries.
AB  - A hierarchical mesoporous TiO2 nanowire bundles (HM-TiO2-NB) superstructure with
      amorphous surface and straight nanochannels has been designed and synthesized
      through a templating method at a low temperature under acidic and wet conditions.
      The obtained HM-TiO2-NB superstructure demonstrates high reversible capacity,
      excellent cycling performance, and superior rate capability. Most importantly, a
      self-improving phenomenon of Li+ insertion capability based on two simultaneous
      effects, the crystallization of amorphous TiO2 and the formation of Li2Ti2O4
      crystalline dots on the surface of TiO2 nanowires, has been clearly revealed
      through ex situ transmission electron microcopy (TEM), high-resolution
      transmission electron microscopy (HRTEM), X-ray diffraction (XRD), Raman, and X
      ray photoelectron spectroscopy (XPS) techniques during the Li+ insertion process.
      When discharged for 100 cycles at 1 C, the HM-TiO2-NB exhibits a reversible
      capacity of 174 mA h g-1. Even when the current density is increased to 50 C, a
      very stable and extraordinarily high reversible capacity of 96 mA h g-1 can be
      delivered after 50 cycles. Compared to the previously reported results, both the
      lithium storage capacity and rate capability of our pure TiO2 material without
      any additives are among the highest values reported. The advanced electrochemical
      performance of these HM-TiO2-NB superstructures is the result of the synergistic
      effect of hybriding of amorphous and crystalline (anatase/rutile) phases and
      hierarchically structuring of TiO2 nanowire bundles. Our material could be a very
      promising anodic material for lithium-ion batteries.

PMID- 27708999
TI  - Disorder Control in Crystalline GeSb2Te4 Using High Pressure.
AB  - Electronic phase-change memory devices take advantage of the different
      resistivity of two states, amorphous and crystalline, and the swift transitions
      between them in active phase-change materials (PCMs). In addition to these two
      distinct phases, multiple resistive states can be obtained by tuning the atomic
      disorder in the crystalline phase with heat treatment, because the disorder can
      lead to the localization of the electronic states and, thus, hamper the electron
      transport. The goal of this work is to achieve and explore multiple disordered
      configurations in PCMs by applying high pressure. Large-scale ab initio molecular
      dynamics simulations demonstrate that pressure can lower the energy barrier for
      the antisite migration in crystalline PCMs. The accumulation of these antisite
      atoms largely increases the compositional disorder, adding localized electronic
      states near the conduction band. The disorder-induced electron localization
      triggered by pressure is a novel way to modulate the properties of materials.
      Furthermore, the random distortion of the lattice induced by the compositional
      disorder provides a new mechanism that contributes to the amorphization of
      crystalline PCMs at high pressure.

PMID- 27709000
TI  - Construction of Efficient 3D Gas Evolution Electrocatalyst for Hydrogen
      Evolution: Porous FeP Nanowire Arrays on Graphene Sheets.
AB  - A novel 3D hierarchical nanocomposite of vertically aligned porous FeP nano-wires
      on reduced graphene oxide is prepared as a demonstration of constructing an
      efficient hydrogen evolution catalyst. Extension of this nanostructuring strategy
      to other functional nanocomposites by combining different dimensional
      nanomaterials is attractive.

PMID- 27709001
TI  - Surface-Amorphous and Oxygen-Deficient Li3VO4-delta as a Promising Anode Material
      for Lithium-Ion Batteries.
AB  - Surface-amorphous and oxygen-deficient Li3VO4-deltasynthesized by simple
      annealing of Li3VO4 powders in a vacuum shows great enhancements in both
      reversible capacity and coulombic efficiency for the first discharge/charge
      without delicate size control and carbon coating. The results are associated with
      the improved charge-transfer kinetics caused by the amorphous surface of Li3VO4
      delta .

PMID- 27709003
TI  - Editor Profiles: Guest Editors of Special Issue on Drug Metabolism and
      Pharmacokinetics.

PMID- 27709002
TI  - Simple 3D Printed Scaffold-Removal Method for the Fabrication of Intricate
      Microfluidic Devices.
AB  - An easy and cheap fabrication method for intricate polydimethylsiloxane
      microfluidic devices is presented. The acrylonitrile butadiene styrene scaffold
      removal method uses cheap, off-the-shelf materials and equipment for the
      fabrication of intricate microfluidic devices. The versatility of the method is
      proven by the fabrication of 3D multilayer, ship-in-a-bottle, selective heating,
      sensing, and NMR microfluidic devices. The methodology is coined ESCARGOT:
      Embedded SCAffold RemovinG Open Technology.

PMID- 27709004
TI  - Advanced knowledge in drug metabolism and pharmacokinetics.

PMID- 27709005
TI  - Renal drug transporters and their significance in drug-drug interactions.
AB  - The kidney is a vital organ for the elimination of therapeutic drugs and their
      metabolites. Renal drug transporters, which are primarily located in the renal
      proximal tubules, play an important role in tubular secretion and reabsorption of
      drug molecules in the kidney. Tubular secretion is characterized by high
      clearance capacities, broad substrate specificities, and distinct charge
      selectivity for organic cations and anions. In the past two decades, substantial
      progress has been made in understanding the roles of transporters in drug
      disposition, efficacy, toxicity and drug-drug interactions (DDIs). In the kidney,
      several transporters are involved in renal handling of organic cation (OC) and
      organic anion (OA) drugs. These transporters are increasingly recognized as the
      target for clinically significant DDIs. This review focuses on the functional
      characteristics of major human renal drug transporters and their involvement in
      clinically significant DDIs.

PMID- 27709006
TI  - An update on the role of intestinal cytochrome P450 enzymes in drug disposition.
AB  - Oral administration is the most commonly used route for drug treatment.
      Intestinal cytochrome P450 (CYP)-mediated metabolism can eliminate a large
      proportion of some orally administered drugs before they reach systemic
      circulation, while leaving the passage of other drugs unimpeded. A better
      understanding of the ability of intestinal P450 enzymes to metabolize various
      clinical drugs in both humans and preclinical animal species, including the
      identification of the CYP enzymes expressed, their regulation, and the relative
      importance of intestinal metabolism compared to hepatic metabolism, is important
      for improving bioavailability of current drugs and new drugs in development.
      Here, we briefly review the expression of drug-metabolizing P450 enzymes in the
      small intestine of humans and several preclinical animal species, and provide an
      update of the various factors or events that regulate intestinal P450 expression,
      including a cross talk between the liver and the intestine. We further compare
      various clinical and preclinical approaches for assessing the impact of
      intestinal drug metabolism on bioavailability, and discuss the utility of the
      intestinal epithelium-specific NADPH-cytochrome P450 reductase-null (IECN) mouse
      as a useful model for studying in vivo roles of intestinal P450 in the
      disposition of orally administered drugs.

PMID- 27709007
TI  - Isoniazid metabolism and hepatotoxicity.
AB  - Isoniazid (INH) is highly effective for the management of tuberculosis. However,
      it can cause liver injury and even liver failure. INH metabolism has been thought
      to be associated with INH-induced liver injury. This review summarized the
      metabolic pathways of INH and discussed their associations with INH-induced liver
      injury.

PMID- 27709009
TI  - Fatty liver diseases, bile acids, and FXR.
AB  - The prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide has
      increased at an alarming rate, which will likely result in enormous medical and
      economic burden. NAFLD presents as a spectrum of liver diseases ranging from
      simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and
      even to hepatocellular carcinoma (HCC). A comprehensive understanding of the
      mechanism(s) of NAFLD-to-NASH transition remains elusive with various genetic and
      environmental susceptibility factors possibly involved. An understanding of the
      mechanism may provide novel strategies in the prevention and treatment to NASH.
      Abnormal regulation of bile acid homeostasis emerges as an important mechanism to
      liver injury. The bile acid homeostasis is critically regulated by the farnesoid
      X receptor (FXR) that is activated by bile acids. FXR has been known to exert
      tissue-specific effects in regulating bile acid synthesis and transport. Current
      investigations demonstrate FXR also plays a principle role in regulating lipid
      metabolism and suppressing inflammation in the liver. Therefore, the future
      determination of the molecular mechanism by which FXR protects the liver from
      developing NAFLD may shed light to the prevention and treatment of NAFLD.

PMID- 27709011
TI  - Exposure to inorganic arsenic can lead to gut microbe perturbations and
      hepatocellular carcinoma.
AB  - Arsenic is a carcinogenic environmental factor found in food and drinking water
      around the world. The mechanisms in which arsenic alters homeostasis are not
      fully understood. Over the past few decades, light has been shed on varying
      mechanisms in which arsenic induces cancer. Such mechanisms include gut microbe
      perturbations, genotoxic effects, and epigenetic modification. Gut microbe
      perturbations have been shown to increase the level of pathogen-associated
      molecular patterns such as lipopolysaccharide (LPS) leading to uncontained
      inflammation. Increase in inflammation is the major factor in cirrhosis leading
      to hepatocellular carcinoma. Alterations in gut permeability and metabolites have
      also been observed as a fallout of arsenic induced gut microbe modification. The
      guts proximity and interaction through portal flow make the liver susceptible to
      gut perturbations and ensuing inflammatory responses. Genotoxic and epigenetic
      dysregulation induced by arsenic and its toxic metabolites present a more direct
      mechanism that works synergistically with gut microbe perturbations to induce the
      incidence of cancers. These pathways combined could be some of the main causes of
      arsenic-induced carcinogenesis.

PMID- 27709008
TI  - Crosstalk of HNF4alpha with extracellular and intracellular signaling pathways in
      the regulation of hepatic metabolism of drugs and lipids.
AB  - The liver is essential for survival due to its critical role in the regulation of
      metabolic homeostasis. Metabolism of xenobiotics, such as environmental chemicals
      and drugs by the liver protects us from toxic effects of these xenobiotics,
      whereas metabolism of cholesterol, bile acids (BAs), lipids, and glucose provide
      key building blocks and nutrients to promote the growth or maintain the survival
      of the organism. As a well-established master regulator of liver development and
      function, hepatocyte nuclear factor 4 alpha (HNF4alpha) plays a critical role in
      regulating a large number of key genes essential for the metabolism of
      xenobiotics, metabolic wastes, and nutrients. The expression and activity of
      HNF4alpha is regulated by diverse hormonal and signaling pathways such as growth
      hormone, glucocorticoids, thyroid hormone, insulin, transforming growth factor
      beta, estrogen, and cytokines. HNF4alpha appears to play a central role in
      orchestrating the transduction of extracellular hormonal signaling and
      intracellular stress/nutritional signaling onto transcriptional changes in the
      liver. There have been a few reviews on the regulation of drug metabolism, lipid
      metabolism, cell proliferation, and inflammation by HNF4alpha. However, the
      knowledge on how the expression and transcriptional activity of HNF4alpha is
      modulated remains scattered. Herein I provide comprehensive review on the
      regulation of expression and transcriptional activity of HNF4alpha, and how
      HNF4alpha crosstalks with diverse extracellular and intracellular signaling
      pathways to regulate genes essential in liver pathophysiology.

PMID- 27709014
TI  - Role of farnesoid X receptor in establishment of ontogeny of phase-I drug
      metabolizing enzyme genes in mouse liver.
AB  - The expression of phase-I drug metabolizing enzymes in liver changes dramatically
      during postnatal liver maturation. Farnesoid X receptor (FXR) is critical for
      bile acid and lipid homeostasis in liver. However, the role of FXR in regulating
      ontogeny of phase-I drug metabolizing genes is not clear. Hence, we applied RNA
      sequencing to quantify the developmental expression of phase-I genes in both Fxr
      null and control (C57BL/6) mouse livers during development. Liver samples of male
      C57BL/6 and Fxr-null mice at 6 different ages from prenatal to adult were used.
      The Fxr-null showed an overall effect to diminish the "day-1 surge" of phase-I
      gene expression, including cytochrome P450s at neonatal ages. Among the 185 phase
      I genes from 12 different families, 136 were expressed, and differential
      expression during development occurred in genes from all 12 phase-I families,
      including hydrolysis: carboxylesterase (Ces), paraoxonase (Pon), and epoxide
      hydrolase (Ephx); reduction: aldoketo reductase (Akr), quinone oxidoreductase
      (Nqo), and dihydropyrimidine dehydrogenase (Dpyd); and oxidation: alcohol
      dehydrogenase (Adh), aldehyde dehydrogenase (Aldh), flavin monooxygenases (Fmo),
      molybdenum hydroxylase (Aox and Xdh), cytochrome P450 (P450), and cytochrome P450
      oxidoreductase (Por). The data also suggested new phase-I genes potentially
      targeted by FXR. These results revealed an important role of FXR in regulation of
      ontogeny of phase-I genes.

PMID- 27709012
TI  - PXR variants: the impact on drug metabolism and therapeutic responses.
AB  - The pregnane X receptor (PXR) plays an important and diverse role in mediating
      xenobiotic induction of drug-metabolizing enzymes and transporters. Several
      protein isoforms of PXR exist, and they have differential transcriptional
      activity upon target genes; transcript variants 3 (PXR3) and 4 (PXR4) do not
      induce target gene expression, whereas transcript variants 1 (PXR1) and 2 (PXR2)
      respond to agonist by activating target gene expression. PXR protein variants
      also display differences in protein-protein interactions; PXR1 interacts with
      p53, whereas PXR3 does not. Furthermore, the transcript variants of PXR that
      encode these protein isoforms are differentially regulated by methylation and
      deletions in the respective promoters of the variants, and their expression
      differs in various human cancers and also in cancerous tissue compared to
      adjacent normal tissues. PXR1 and PXR4 mRNA are downregulated by methylation in
      cancerous tissue and have divergent effects on cellular proliferation when
      ectopically overexpressed. Additional detailed and comparative mechanistic
      studies are required to predict the effect of PXR transcript variant expression
      on carcinogenesis, therapeutic response, and the development of toxicity.

PMID- 27709010
TI  - Insights into CYP2B6-mediated drug-drug interactions.
AB  - Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug
      metabolism than was previously believed. The discovery of multiple important
      substrates of CYP2B6 as well as polymorphic differences has sparked increasing
      interest in the genetic and xenobiotic factors contributing to the expression and
      function of the enzyme. The expression of CYP2B6 is regulated primarily by the
      xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X
      receptor (PXR) in the liver. In addition to CYP2B6, these receptors also mediate
      the inductive expression of CYP3A4, and a number of important phase II enzymes
      and drug transporters. CYP2B6 has been demonstrated to play a role in the
      metabolism of 2%-10% of clinically used drugs including widely used
      antineoplastic agents cyclophosphamide and ifosfamide, anesthetics propofol and
      ketamine, synthetic opioids pethidine and methadone, and the antiretrovirals
      nevirapine and efavirenz, among others. Significant inter-individual variability
      in the expression and function of the human CYP2B6 gene exists and can result in
      altered clinical outcomes in patients receiving treatment with CYP2B6-substrate
      drugs. These variances arise from a number of sources including genetic
      polymorphism, and xenobiotic intervention. In this review, we will provide an
      overview of the key players in CYP2B6 expression and function and highlight
      recent advances made in assessing clinical ramifications of important CYP2B6
      mediated drug-drug interactions.

PMID- 27709013
TI  - A brief history of the discovery of PXR and CAR as xenobiotic receptors.
AB  - The nuclear receptors pregnane X receptor (PXR) and constitutive androstane
      receptor (CAR) were cloned and/or established as xenobiotic receptors in 1998.
      Due to their activities in the transcriptional regulation of phase I and phase II
      enzymes as well as drug transporters, PXR and CAR have been defined as the master
      regulators of xenobiotic responses. The discovery of PXR and CAR provides the
      essential molecular basis by which drugs and other xenobiotic compounds regulate
      the expression of xenobiotic enzymes and transporters. This article is intended
      to provide a historical overview on the discovery of PXR and CAR as xenobiotic
      receptors.

PMID- 27709015
TI  - Tissue distribution and tumor uptake of folate receptor-targeted epothilone
      folate conjugate, BMS-753493, in CD2F1 mice after systemic administration.
AB  - To assess targeting of an epothilone folate conjugate (BMS-753493) to the folate
      receptor (FR)-overexpressed tumor in mice bearing both FR+ and FR- tumors, a
      series of experiments were conducted by quantitative whole-body autoradiography
      (QWBA) and LC-MS/MS following i.v. administration of BMS-753493 or its active
      moiety, BMS-748285 in mice bearing FR+ (98M109) and FR- (M109) tumors. QWBA
      showed [3H]BMS-753493-derived radioactivity was extensively distributed to
      various tissues. The FR over-expressing 98M109 tumors showed consistently higher
      level of radioactivity than FR-negative tumors (i.e., M109 tumors) up to 48 h
      post dose of [3H]BMS-753493, despite the magnitude of difference between the
      tumors is relatively small (generally 3~5-fold). The radioactivity level in
      98M109 tumors was 2~12-fold of normal tissues except intestine/content at 48 h
      post dose. No selective radioactivity uptake into 98M109 tumors over M109 or
      normal tissues was observed after i.v. administration of the active epothilone,
      [3H]BMS-748285. LC-MS/MS measurements demonstrated that the concentrations of BMS
      748285, presumably from hydrolysis of the folate conjugate, in 98M109 tumors were
      greater than those in M109 tumors after i.v. administration of BMS-753493 (2-3
      fold) whereas no differential uptake in the tumors following BMS-748285
      administration. Those data were consistent with radioactivity determinations.
      Those results demonstrated that the folate conjugation in BMS-753493 enabled
      moderately preferential distribution of the active epothilone to FR over
      expressing 98M109 tumors, thereby supporting targeted delivery of cytotoxics
      through the folate receptor.

PMID- 27709016
TI  - Effect of age on the pharmacokinetics of polymorphic nimodipine in rats after
      oral administration.
AB  - The previous investigation has proved that their existed pharmacokinetic
      difference between the different crystal forms of the polymorphic drugs after
      oral administration. However, no systemic investigations have been made on the
      change of this pharmacokinetic difference, resulted either from the physiological
      or from the pathological factors. In this paper, we used polymorphic nimodipine
      (Nim) as a model drug and investigated the effect of age difference (2- and 9
      month old) on the pharmacokinetics after oral delivery in rats. As the results
      shown, for L-form of Nim (L-Nim), the AUC0-24 h in 2-month-old rats was 343.68+/
      47.15 ng.h/mL, which is 23.36% higher than that in 9-month-old rats. For H-form
      of Nim (H-Nim), the AUC0-24 h in 2-month-old rats was 140.91+/-19.47 ng.h/mL,
      which is 54.64% higher than that in 9-month-old rats. The AUC0-24 h ratio between
      H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats. Since
      age difference could result in unparallelled change of the absorption and
      bioavailability of the polymorphic drugs, the results in this experiment are of
      value for further investigation of crystal form selection in clinical trials and
      rational clinical application of the polymorphic drugs.

PMID- 27709017
TI  - Characterizing drug-metabolizing enzymes and transporters that are bona fide CAR
      target genes in mouse intestine.
AB  - Intestine is responsible for the biotransformation of many orally-exposed
      chemicals. The constitutive androstane receptor (CAR/Nr1i3) is known to up
      regulate many genes encoding drug-metabolizing enzymes and transporters (drug
      processing genes/DPGs) in liver, but less is known regarding its effect in
      intestine. Sixty-day-old wild-type and Car-/- mice were administered the CAR
      ligand TCPOBOP or vehicle once daily for 4 days. In wild-type mice, Car mRNA was
      down-regulated by TCPOBOP in liver and duodenum. Car-/- mice had altered basal
      intestinal expression of many DPGs in a section-specific manner. Consistent with
      the liver data (Aleksunes and Klaassen, 2012), TCPOBOP up-regulated many DPGs
      (Cyp2b10, Cyp3a11, Aldh1a1, Aldh1a7, Gsta1, Gsta4, Gstm1-m4, Gstt1, Ugt1a1,
      Ugt2b34, Ugt2b36, and Mrp2-4) in specific sections of small intestine in a CAR
      dependent manner. However, the mRNAs of Nqo1 and Papss2 were previously known to
      be up-regulated by TCPOBOP in liver but were not altered in intestine.
      Interestingly, many known CAR-target genes were highest expressed in colon where
      CAR is minimally expressed, suggesting that additional regulators are involved in
      regulating their expression. In conclusion, CAR regulates the basal expression of
      many DPGs in intestine, and although many hepatic CAR-targeted DPGs were bona
      fide CAR-targets in intestine, pharmacological activation of CAR in liver and
      intestine are not identical.

PMID- 27709020
TI  - Editorial of Virtual Special Issue on Progress in Medicinal Chemistry.

PMID- 27709018
TI  - Development of a mechanism-based pharmacokinetic/pharmacodynamic model to
      characterize the thermoregulatory effects of serotonergic drugs in mice.
AB  - We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor
      (MAOI), potentiates serotonin (5-HT) receptor agonist 5-methoxy-N,N
      dimethyltryptamine (5-MeO-DMT)-induced hyperthermia. The objective of this study
      was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD) model to
      characterize and predict the thermoregulatory effects of such serotonergic drugs
      in mice. Physiological thermoregulation was described by a mechanism-based
      indirect-response model with adaptive feedback control. Harmaline-induced
      hypothermia and 5-MeO-DMT-elicited hyperthermia were attributable to the loss of
      heat through the activation of 5-HT1A receptor and thermogenesis via the
      stimulation of 5-HT2A receptor, respectively. Thus serotonergic 5-MeO-DMT-induced
      hyperthermia was readily distinguished from handling/injection stress-provoked
      hyperthermic effects. This PK/PD model was able to simultaneously describe all
      experimental data including the impact of drug-metabolizing enzyme status on 5
      MeO-DMT and harmaline PK properties, and drug- and stress-induced simple
      hypo/hyperthermic and complex biphasic effects. Furthermore, the modeling results
      revealed a 4-fold decrease of apparent SC50 value (1.88-0.496 umol/L) for 5-MeO
      DMT when harmaline was co-administered, providing a quantitative assessment for
      the impact of concurrent MAOI harmaline on 5-MeO-DMT-induced hyperthermia. In
      addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5
      MeO-DMT were linked to the increased systemic exposure to harmaline rather than 5
      MeO-DMT, although the body temperature profiles were mispredicted by the model.
      The results indicate that current PK/PD model may be used as a new conceptual
      framework to define the impact of serotonergic agents and stress factors on
      thermoregulation.

PMID- 27709021
TI  - Fungistatic effect of hydroxychloroquine, lessons from a case.
AB  - A 50-year-old male was prescribed with hydroxychloroquine (HCQ) after
      osteoarthritis was diagnosed. He had an old nail infection of Aspergillus niger.
      A remarkable improvement of the symptoms of fungal nail infection was seen after
      about four weeks of treatment with HCQ. It was very hard to detect the symptoms
      in the end of the second month of the treatment, both in the finger and toe
      nails. The symptoms were clearly recurred after HCQ was discontinued.

PMID- 27709019
TI  - 17beta-Estradiol up-regulates UDP-glucuronosyltransferase 1A9 expression via
      estrogen receptor alpha.
AB  - UDP-glucuronosyltransferase 1A9 (UGT1A9) is a major phase II enzyme responsible
      for elimination of drugs and endogenous molecules. Clinical data have shown
      increased elimination of UGT1A9 substrates in pregnant women or oral
      contraceptive users, but the role of estrogen in the regulation of UGT1A9
      expression remains unknown. In this study, we investigated the effect of 17beta
      estradiol (E2) on UGT1A9 expression and the role of ERalpha in the
      transcriptional regulation of UGT1A9. E2 significantly increased UGT1A9 promoter
      activity in HepG2 cells in the presence of ERalpha. UGT1A9 induction by E2 was
      abrogated by antiestrogen ICI182,780 in HepG2 cells that constitutively express
      ERalpha. Results from transient transfection of ERalpha mutants into HepG2 cells
      demonstrated that mutation at DNA-binding domain of ERalpha abrogates increased
      UGT1A9 promoter activity by E2. Deletion and mutation assays of UGT1A9 promoter
      revealed a putative ERE located within -2262/-1987 region. Examination of healthy
      human liver tissues revealed significantly higher UGT1A9 expression in women as
      compared to men. Together, these findings provide a mechanistic basis for the
      previous clinical reports and may shed a light on identifying sources for inter
      individual variability in UGT1A9-mediated drug metabolism.

PMID- 27709022
TI  - Arthroscopic Repair of Inferior Labrum Anterior to Posterior Lesions of the
      Shoulder Using a Combined "Double-Pulley" Simple Knot Technique.
AB  - Inferior labrum anterior to posterior lesions as an isolated injury or as part of
      an extensive traumatic labral tear are uncommon and may present as
      multidirectional instability of the shoulder. These lesions are hard to visualize
      radiographically and many times are diagnosed only during surgery. Arthroscopic
      repair of these lesions requires advanced arthroscopic skills and is required for
      restoration of glenohumeral stability. We report a combined double-pulley simple
      knot technique that anatomically reconstructs the inferior labrum while
      overcoming the typical technical challenges, providing a large footprint for
      healing along the inferior glenoid rim and minimizing the amount of suture
      material in direct contact with the articular cartilage and the risk of knot
      migration.

PMID- 27709023
TI  - Percutaneous Reconstruction of the Anterolateral Ligament of the Knee With a
      Polyester Tape.
AB  - Recent advances in surgeons' understanding of the anatomic, biomechanical, and
      radiologic features of the anterolateral ligament (ALL) of the knee have led to
      an increased interest in reconstruction of this structure as part of the
      management of knee instability. Even without any technical flaws and proper
      positioning of the bone tunnels, there is a small subset of patients,
      approximately 7% of all patients, who experience some residual anterolateral
      rotational instability after anterior cruciate ligament reconstruction. For this
      reason, some researchers have turned again toward the anterolateral aspect of the
      knee and specifically the ALL. In this technical note, the surgical steps for
      percutaneous reconstruction of ALL of the knee using a polyester tape are
      described.

PMID- 27709024
TI  - Revision Lapidus Arthrodesis by Bone Endoscopy.
AB  - Revision arthrodesis is indicated in symptomatic nonunion of the first
      tarsometatarsal joint. Revision by first tarsometatarsal arthroscopy cannot deal
      with the dilated screw tract and associated bone cysts. Revision by bone
      endoscopy is indicated in symptomatic nonunion of the first tarsometatarsal
      joint, which is previously fixed by transarticular screw along with loosening of
      the screw and bone cyst formation. The screw tract makes up the portal tract,
      with the proximal and distal ends of the tract corresponding to the proximal and
      distal portals, respectively. In this technical note, we describe zonal
      debridement and bone grafting of the bone cysts, nonunion site, and the screw
      tract via the bone endoscopy. This can resolve all the co-pathologies of nonunion
      of the first tarsometatarsal fusion.

PMID- 27709025
TI  - Arthroscopic Radial Head Implant Removal and Resection.
AB  - Displaced radial head fractures are treated with open reduction and internal
      fixation using implants. Failure of fixation may occur in the presence of
      comminution and in multifragmentary fractures; open surgical approaches are
      necessary for removal of the implants and radial head resection. Arthroscopic
      radial head resection has been described as a minimally invasive and effective
      treatment for failed radial head fracture fixation; however, periarticular
      adhesions and prominent implants add to the complexity and technical difficulty
      of the procedure. The described technique uses 3 portals for adhesiolysis,
      implant removal, and radial head resection. Resection is performed in stages;
      smaller-diameter instruments are used to gain and improve access, and larger
      resectors are used subsequently. Adequacy of resection is assessed
      arthroscopically and with biplanar imaging. The arthroscopic technique avoids the
      need for an open surgical approach and prevents subsequent morbidity. In
      addition, the rehabilitation time is shorter and patient satisfaction is high.

PMID- 27709026
TI  - Integral Suture-Handling Techniques for Arthroscopic Sliding Knots.
AB  - In arthroscopic tissue repair, the final step is achieving adequate tissue
      approximation with a secure knot. The sliding knot is widely preferred over the
      nonsliding knot, with numerous publications describing knot configurations.
      However, in the literature there are few published descriptions of suture
      handling techniques, even though they are fundamental to arthroscopic knot tying.
      We describe integral suture-handling techniques for arthroscopic sliding knots to
      improve the surgeon's performance in knot tying.

PMID- 27709027
TI  - "Owl" Technique for All-Arthroscopic Augmentation of a Massive or Large Rotator
      Cuff Tear With Extracellular Matrix Graft.
AB  - Despite the vast improvement in techniques and technology for arthroscopic
      rotator cuff surgery, repairs of massive and large tears remain challenging
      because they are associated with significantly high failure rates. In recent
      years, patch augmentation has gained popularity as a technique to decrease these
      high failure rates. Arthroscopic patch augmentation of rotator cuff repair,
      however, is technically difficult. The purpose of this report is to describe a
      simple and reproducible technique for all-arthroscopic extracellular matrix graft
      augmentation. With this technique, which we refer to as the "owl" technique
      because the prepared extracellular augment resembles an owl, there are relatively
      few suture ends involved; therefore, augment introduction is straightforward with
      a reduced risk of suture ends becoming tangled. In addition, the way in which our
      augmentation is prepared helps to prevent it from becoming bunched up when being
      secured.

PMID- 27709028
TI  - Distal Femoral Osteotomy: Lateral Opening Wedge Technique.
AB  - Coronal limb malalignment is a significant contributor to asymmetric joint wear,
      gait abnormalities, and the development and progression of degenerative joint
      disease. Osteotomies about the knee were developed to realign the mechanical axis
      of the limb to unload the affected compartment. Valgus malalignment is less
      common than varus malalignment, but can contribute to a variety of clinical
      conditions, including lateral compartment cartilage defects and arthritis,
      lateral patellofemoral instability, and medial collateral ligament laxity. In
      this article, we describe our preferred operative technique for a lateral opening
      wedge varus-producing distal femoral osteotomy to correct mild to moderate valgus
      malalignment.

PMID- 27709029
TI  - Basic Shoulder Arthroscopy: Beach Chair Patient Positioning.
AB  - Shoulder arthroscopy is an orthopaedic procedure that has grown significantly in
      popularity over the last 40 years. The 2 principle patient positions during
      shoulder arthroscopy include the beach chair position and lateral decubitus
      position. This Technical Note details the operating room setup for shoulder
      arthroscopy in the beach chair position. Proper positioning for this procedure
      will minimize potential complications and facilitate ease of surgical
      intervention.

PMID- 27709030
TI  - Anatomic Arthroscopic Ligamentum Teres Reconstruction for Hip Instability.
AB  - There has been growing interest in recent years on the functional importance of
      the ligamentum teres and its role in hip stability. Partial or complete tearing
      has previously been treated with debridement or radiofrequency ablation with good
      results; however, a subset of patients will continue to experience persistent
      pain or instability with injury to this structure. Advances in arthroscopic
      instruments and techniques have led to our ability to provide improved care for
      these patients by performing a ligamentum teres reconstruction. The purpose of
      this technical note is to describe our method of ligamentum teres reconstruction
      with a tibialis anterior allograft.

PMID- 27709031
TI  - Arthroscopic Femoral Osteochondroplasty for Cam-Type Femoroacetabular
      Impingement: The Trough Technique.
AB  - Arthroscopic osteochondroplasty has become the most common treatment for cam-type
      femoroacetabular impingement. However, gauging the appropriate depth and location
      of the femoral osteochondroplasty remains challenging, given the parallax
      observed from using a 70 degrees  arthroscope across multiple viewing
      perspectives. Consequently, reliable techniques must use a combination of
      arthroscopic and fluoroscopic checks and balances to assess the femoral head-neck
      junction to help guide bony resection. We have developed a technique for
      osteochondroplasty that has made the process more efficient and reliable in our
      hands. It involves creating a trough at the apex of the osteochondroplasty and
      then contouring the proximal and distal regions to re-create normal proximal
      femoral geometry. This article details our technique for femoral
      osteochondroplasty, which can be performed alone for isolated cam impingement or
      in concert with other intra- and extra-articular procedures to address associated
      hip pathology.

PMID- 27709032
TI  - Extensor Tendoscopy of the Wrist.
AB  - Extensor tenosynovitis of the wrist can lead to rupture of the extensor tendons.
      Extensor tenosynovectomy is indicated if the tenosynovitis cannot be controlled
      by conservative measures. Open tenosynovectomy requires extensive dissection of
      soft tissue, including the extensor retinaculum. This article describes extensor
      tendoscopy of the wrist. This technique allows approach to the extensor
      compartments with small incisions and minimal soft tissue dissection. It is
      indicated when extensor tenosynovitis persists despite adequate medical
      treatments including medications, immobilization, and steroid injection.
      Synovectomy of the extensor compartments can be performed with preservation of
      the extensor retinaculum. This technique is contraindicated if the wrist cannot
      be flexed or there is severe tendinopathy of the extensor tendon that may need
      open reconstruction. The purpose of this technical note was to describe a
      minimally invasive approach of complete synovectomy of the extensor compartments
      with preservation of the extensor compartment.

PMID- 27709034
TI  - Posterior Horn of Medial Meniscal Peripheral Capsular Lesion: The Arthroscopic
      Repair Technique Working in the Posterior Compartment.
AB  - A posterior horn of medial meniscal peripheral capsular is usually associated
      with the anterior cruciate ligament injury. The conventional repair technique
      with the camera in the anterolateral portal cannot precisely restore the slope
      capsular synovium to the original attachment point. We present the arthroscopic
      technique for improving the accuracy and quality of the repair by working in the
      posterior compartment. When the posterolateral portal is used as the viewing
      portal, the accuracy of repair is improved because we can assess the full extent
      of the lesion and lift the sagging peripheral tissue to the more central part.

PMID- 27709033
TI  - Surgical Adjustment of the Guide Pin to Perform a Correct Tibial Tunnel in
      Anatomical Anterior Cruciate Ligament Single-Bundle Reconstruction.
AB  - Anatomical positioning of the graft in anterior cruciate ligament reconstruction
      is important to restore normal knee kinematics and prevent early joint
      degeneration. Inadequate position of a first attempt to place the guide pin
      within the center of the tibial footprint may occur. Therefore, its adjustment is
      important to achieve the anatomical positioning of the graft within the tibial
      footprint. When the guide pin exits eccentrically in an inadequate position, it
      is possible to correct it to the center of the footprint. A small tunnel with a
      4.5-mm reamer is made and the guide pin is shifted to the center of the
      footprint. The center of the tunnel can be corrected until 50% and in all
      direction in relation to the initial drilled tunnel, without additional
      associated morbidity. Once the correct position of the center is achieved, the
      guide pin is fixed in the femoral notch roof to guarantee the accurate correction
      of the axis, without toggling of the guide pin inside the tunnel and metal
      dusting. The final tunnel is then drilled with the same size of the graft. With
      this technique it is possible to adjust an eccentrically misplaced guide pin to
      the center of the footprint without additional morbidity.

PMID- 27709035
TI  - Opening-Wedge Proximal Tibial Osteotomy.
AB  - Varus knee malalignment caused by medial compartment arthritis results in
      progressive asymmetric wear of the tibiofemoral joint. This wear can cause
      progressively painful gonarthrosis. Surgical methods to address varus knee
      malalignment include lateral closing-wedge proximal tibial osteotomy, medial
      opening-wedge osteotomy, and arthroplasty. Medial opening-wedge proximal tibial
      osteotomy is an effective procedure for restoring proper coronal alignment and
      reducing knee pain. In this technical note, we present a reproducible technique
      for proximal tibial osteotomy.

PMID- 27709036
TI  - Modified Arthroscopic Brostrom Procedure With Bone Tunnels.
AB  - The open anatomic repair of the anterior talofibular and calcaneofibular
      ligaments (modified Brostrom procedure) is widely accepted as the standard
      surgical stabilization procedure for lateral ankle instability that does not
      respond to conservative measures. Arthroscopic Brostrom procedures with a suture
      anchor have been reported to achieve both anatomic repair of the lateral ankle
      ligaments and management of the associated intra-articular lesions. However, the
      complication rates are higher than open Brostom procedures. Many of these
      complications are associated with the use of a suture anchor. We report a
      modified arthroscopic Brostrom procedure in which the anterolateral ankle capsule
      is anchored to the lateral malleolus through small bone tunnels instead of suture
      anchors.

PMID- 27709037
TI  - Outside-In Deep Medial Collateral Ligament Release During Arthroscopic Medial
      Meniscus Surgery.
AB  - Arthroscopic partial medial meniscectomy is a very common orthopaedic procedure
      performed for symptomatic, irreparable meniscus tears. It is usually associated
      with a very good outcome and minimal complications. In some patients with tight
      medial compartment, the posterior horn of the medial meniscus can be difficult to
      visualize, and access in this area with instruments may be challenging. To
      increase the opening of the medial compartment, after valgus-extension stress
      position of the knee, different techniques of deep medial collateral ligament
      release have been described. The outside-in pie-crusting technique shown in this
      technical note has documented effectiveness and good outcomes with minimal or no
      morbidity.

PMID- 27709038
TI  - Bicruciate Knee Ligament Reconstruction Using 4 All-Anterior Arthroscopic
      Portals.
AB  - The use of an accessory posteromedial portal for posterior cruciate ligament
      reconstruction in bicruciate knee ligament reconstruction has often been
      described. However, the use of a posteromedial portal can be time consuming and
      has some inherent risks including injury to the saphenous vein or nerve. We
      describe our bicruciate knee ligament reconstruction using 4 exclusively anterior
      portals including a high anteromedial, high anterolateral, low anteromedial, and
      low anterolateral portals. Arthroscopy is performed using a combination of 30
      degrees  and 70 degrees  arthroscopes. Fluoroscopic assistance is used in
      conjunction with a 70 degrees  arthroscope for the creation of the posterior
      cruciate ligament tibial tunnel.

PMID- 27709039
TI  - Inside-Out Repair for Radial Meniscus Tears.
AB  - Understanding of meniscal function through basic science, natural history, and
      biomechanics has highlighted the importance of preserving the meniscus to
      maintain normal knee biomechanics. Tears that may alter these biomechanics can
      contribute to the progressive nature of degenerative joint disease in the knee.
      Radial tears result in the disruption of the circumferential fibers causing
      inability of the native meniscus to resist normal hoop stresses, thereby leading
      to increased focal areas of pressure that cause complications such as early onset
      arthrosis. In this technical note, we describe our preferred operative technique
      to repair radial meniscal tears using an arthroscopic inside-out approach with
      satisfactory clinical outcomes and healing response.

PMID- 27709040
TI  - Varus-Producing Lateral Distal Femoral Opening-Wedge Osteotomy.
AB  - Valgus knee alignment in excess of physiological valgus leads to excessive
      loading of the lateral compartment, which can potentially increase the risk of
      osteoarthritis and can place the medial knee structures at risk of chronic
      attenuation. Varus-producing distal femoral osteotomies have been proposed for
      correction of valgus malalignment, to relieve tension on medial-sided structures,
      as well as to off-load the lateral compartment. Understanding that symptomatic
      valgus deformity of the knee represents a complex problem that is magnified in
      the setting of lateral compartment arthritis or medial ligamentous incompetence,
      we present our preferred technique for a varus-producing distal femoral osteotomy
      using plate osteosynthesis and cancellous bone allograft.

PMID- 27709041
TI  - Anatomic Anterior Cruciate Ligament Reconstruction: The Use of the Anterior Horn
      of the Lateral Meniscus as a Guide to Tibial Tunnel Placement.
AB  - Anatomic anterior cruciate ligament reconstruction has been shown to reduce the
      risk of graft failure and to improve patient-related clinical outcomes. The
      posterior border of the anterior horn of the lateral meniscus is a useful marker
      for anatomic tibial tunnel placement. Assessment of a preoperative magnetic
      resonance imaging scan can allow surgical planning of tibial tunnel placement to
      allow for anatomic, patient-specific tibial tunnel placement during anatomic
      anterior cruciate ligament reconstruction. We present this technique to show how
      to use the posterior border of the anterior horn of the lateral meniscus
      clinically.

PMID- 27709042
TI  - Simplified Setup to Achieve Distraction for Toe Arthroscopy.
AB  - Toe arthroscopy has historically had limited applications but is beginning to
      emerge as a viable treatment option for select toe pathologies, and continues to
      have expanding indications as technology and techniques improve. Toe arthroscopy
      has used a multitude of distraction techniques to perform the procedures but all
      have had limited success. Thus, we propose a simple toe arthroscopy distraction
      technique that uses an external positioning arm to allow the surgeon to apply
      manual traction in multiple positions without the use of an assistant, external
      weights, or any reprocessed sterile equipment.

PMID- 27709043
TI  - Endoscopic Gluteus Medius Repair Augmented With Bioinductive Implant.
AB  - Patients with gluteus minimus and medius tears that fail nonoperative management
      may be indicated for surgical repair; however, structural failure after gluteal
      tendon repair remains unacceptably high. This is likely related to the limited
      healing potential of tendinous tissue, which is poorly vascular and heals by
      formation of fibrocartilaginous scar tissue rather than histologically normal
      tendon. An emerging option to augment tendon healing is the use of a bioinductive
      implant that is designed to amplify the host healing response and induce the
      formation of healthy tendon tissue. Though it is rapidly being adopted for
      partial- and full-thickness rotator cuff tears, this implant has not yet been
      used in the hip. A detailed technical description and a discussion of the
      advantages and disadvantages of the technique are provided.

PMID- 27709044
TI  - Anterior Cruciate Ligament Reconstruction With Bone-Patellar Tendon-Bone
      Autograft and a Medial Parapatellar Portal.
AB  - Anterior cruciate ligament (ACL) reconstruction is one of the most extensively
      studied surgical procedures in orthopaedics. The importance of this ligament for
      knee function and stability has been widely studied. For athletes who participate
      in activities involving cutting, twisting, and running, surgical reconstruction
      of the ACL has become the standard of care. However, there is much debate
      regarding the techniques involved in ACL reconstruction, including graft choice,
      technique of drilling the femoral tunnel, and single- versus double-bundle
      reconstruction. In recent studies, ACL femoral tunnel drilling via a medial
      parapatellar or accessory anteromedial portal provides a more anatomic graft
      placement than transtibial femoral drilling. Long-term outcomes of these
      techniques have not been widely studied. This article details our technique for
      ACL reconstruction with bone-patellar tendon-bone autograft and a medial
      parapatellar portal.

PMID- 27709045
TI  - Arthroscopic Rotator Cuff Repair With Concomitant Capsular Release.
AB  - Patients with rotator cuff tears may present with or subsequently develop
      concomitant shoulder stiffness. The treatment of rotator cuff tears in the face
      of passive glenohumeral motion loss is controversial. Preoperative shoulder
      stiffness has been considered by some a contraindication to rotator cuff repair.
      Some surgeons recommend staging surgical procedures and delaying rotator cuff
      repair until shoulder stiffness has resolved. However, this can lead to prolonged
      recovery times and patient dissatisfaction. We describe a surgical technique that
      allows for the single-stage arthroscopic management of rotator cuff tears with
      associated adhesive capsulitis. Arthroscopic capsular release and shoulder
      manipulation are performed in the same operative setting as arthroscopic rotator
      cuff repair. We have found that this combined, single-stage arthroscopic approach
      can effectively treat patients with rotator cuff tears and concomitant shoulder
      stiffness.

PMID- 27709046
TI  - Arthroscopic Double-Row Suture Anchor Repair of Acute Posterior Bony Bankart
      Lesion.
AB  - The treatment of anterior shoulder instability is well described with various
      techniques, including arthroscopic double-row repair, an alternative to open
      stabilization procedures in high-risk groups. The surgical management of
      posterior instability in high-risk and athletic populations is a less-explored
      entity. We describe our technique for an all arthroscopic double-row suture
      anchor repair of a large posterior bony Bankart lesion. We prefer this technique
      over percutaneous cannulated screw fixation because the double-row suture
      technique allows for incorporation of capsular plication with bony fixation in an
      effort to better restore normal anatomy for capsulolabral complex. Double-row
      repair capsulolabral repair or fixation of the bony Bankart is performed via a
      suture-bridge technique. Medial row anchors are placed down the glenoid neck and
      shuttled around the bony fragment and labrum. The lateral-row anchor is placed at
      the rim of the native glenoid. This repair technique has been shown to increase
      the surface area for healing and more closely reconstruct the native anatomic
      capsulolabral complex footprint, improve force distribution, and potentially
      impart enhanced posterior stability to the glenohumeral joint.

PMID- 27709047
TI  - Valgus Extension Overload: Arthroscopic Decompression in the Supine-Suspended
      Position.
AB  - Elbow arthroscopy is a useful tool for managing diseases of the elbow, including
      valgus extension overload, when conservative treatments have failed. Arthroscopic
      access to the elbow in the supine-suspended position is simple and reproducible
      with the technique described in this report. Synovial tissue can be cleared,
      optimizing visualization of the anatomic structures in the elbow including the
      posterior ulnohumeral joint. This report describes, in detail, arthroscopy of the
      elbow in the supine-suspended position and basic principles for arthroscopic
      decompression of the posterior elbow for valgus extension overload.

PMID- 27709048
TI  - Ultrasound-Guided Portal Placement for Hip Arthroscopy.
AB  - Over the past 2 decades, hip arthroscopy has developed as a surgical technique,
      with more orthopaedic surgeons attempting to become proficient in performing this
      surgical procedure as indications and surgical skills evolve. The hip joint
      presents unique arthroscopic challenges because of its anatomic location, and it
      can be challenging to safely and confidently establish portal sites. Ultrasound
      guided hip arthroscopy portal placement is not yet common practice for
      orthopaedic surgeons. The potential advantages of ultrasound-guided hip
      arthroscopy portal placement are the lack of radiation exposure to the patient
      and operating room personnel, direct visualization of the hip joint and
      surrounding soft-tissue structures, and lack of bulky fluoroscopic equipment in
      the operative field. We describe a detailed technique incorporating video
      examples using ultrasound guidance to establish appropriate portal sites for hip
      arthroscopy with the aim to improve safety and overall operator competence.

PMID- 27709049
TI  - The Sliding, Interlocking "8-2-Alpha Knot" for Arthroscopic Surgery.
AB  - We describe a sliding knot that is ideally lockable by transforming the original
      simple figure-of-8 configuration into a true interlocking, low-profile knot with
      an alpha-alpha configuration that creates strong primary knot security when tying
      is finished. Reversed half-hitches on alternating posts for secondary knot
      security can be added, but to save surgical time, these are not obligatory. Three
      simple knot-tying methods are presented; the choice of which to use is based on
      the surgeon's preference. Pulling the loop limb simultaneously on both sides of
      the knot could trigger premature knot flipping. Therefore, the loop limb should
      not be over-tensioned while sliding down the knot; the knot should always be
      "pulled" down, rather than "pushed" down, onto the target tissues. Because all
      loops would be disassembled after the post limb is removed from the knot, a
      salvage procedure is proposed to save the suture from unintentional premature
      locking.

PMID- 27709050
TI  - Arthroscopic Repair of Posterior Glenohumeral Capsular Rupture With Concomitant
      Anterior and Posterior Labrum Detachment.
AB  - Posterior glenohumeral capsular rupture is a rare cause of posterior glenohumeral
      instability. With advances in imaging and arthroscopic techniques, diagnosis and
      treatment of posterior glenohumeral instability are becoming more common in
      practice. We present a technique for arthroscopic repair of a posterior
      glenohumeral capsular rupture with concomitant anterior and posterior labrum
      detachment. Arthroscopic fixation was facilitated by use of a 70 degrees 
      arthroscope through an anterior viewing portal to allow accurate placement of the
      posterior portal in preparation for knot tying. This arthroscopic technique
      resulted in a successful outcome.

PMID- 27709051
TI  - Classification and Surgical Repair of Ramp Lesions of the Medial Meniscus.
AB  - Ramp lesions of the medial meniscus are commonly associated with anterior
      cruciate ligament ruptures and consist of longitudinal peripheral tears of the
      posterior horn of the medial meniscus. Given the frequency of partial-thickness
      tears, they can be difficult to diagnose arthroscopically from the anterior
      compartment. We describe a classification of the different types of ramp lesions
      depending on both tear pattern (partial- or full-thickness tear) and associated
      meniscotibial ligament disruption. An original technique of arthroscopic suture
      placement through a single posteromedial portal with a 25 degrees  curved suture
      hook device is described.

PMID- 27709052
TI  - The Hidden Lesion of the Subscapularis: Arthroscopically Revisited.
AB  - The "hidden lesion" refers to a tear of the subscapularis in the presence of an
      intact biceps pulley or rotator interval. Visualization of these tears during
      open surgery is difficult, yet even with the advancement of arthroscopy,
      visualization can still be challenging. Incomplete visualization of the
      subscapularis could lead to failure to diagnose a tear of the tendon and
      subsequently hinder results after shoulder surgery. With the advancement of
      arthroscopy, a technique to identify these hidden lesions is needed to avoid
      inferior results. We describe an arthroscopic technique to visualize, diagnosis,
      and repair these tears when clinically indicated. Implementing this technique in
      the setting of suspected subscapularis tendon injury can provide complete
      visualization of the tendon insertion.

PMID- 27709053
TI  - Capsular Preservation Using Suture Suspension Technique in Hip Arthroscopy for
      Femoroacetabular Impingement.
AB  - This article describes the use of sutures to enhance visualization while
      protecting the capsule in both the central and peripheral compartments during hip
      arthroscopy. We describe first a technique to preserve the proximal capsule cuff
      while working in the central compartment and then an alternative to the T
      capsulotomy while maintaining excellent visualization of the peripheral
      compartment during femoroplasty of cam-type femoroacetabular impingement. By use
      of suture suspension of the capsule, multiple goals are achieved: The integrity
      of the proximal capsule cuff is maintained while aiding in visualization of the
      central compartment; the iliofemoral ligament is spared, which plays a critical
      role in preventing microinstability; the necessary space is created to obtain
      adequate visualization of the peripheral compartment for complete femoroplasty;
      and operative time is reduced because creation and subsequent repair of the T
      capsulotomy can be avoided.

PMID- 27709054
TI  - Medial Meniscus Radial Tear: A Transtibial 2-Tunnel Technique.
AB  - Complete radial tears of the medial meniscus significantly decrease the meniscal
      tissue's ability to dissipate tibiofemoral loads and have been described as
      functionally similar to a total meniscectomy, predisposing patients to early
      osteoarthritis. At present, no consensus exists regarding the optimal surgical
      treatment of a radial meniscal tear. Current repair techniques have led to a
      reportedly high rate of incomplete healing or healing of the meniscus in a
      nonanatomic, gapped position, which compromises its ability to withstand hoop
      stresses. Improvement regarding the ability to repair and heal medial meniscus
      radial tears has the potential to result in enhanced preservation of the
      articular cartilage in the medial compartment of the knee. This technical
      description details a method for repairing radial tears of the medial meniscus
      using a transtibial 2-tunnel technique.

PMID- 27709055
TI  - Pendulum Exercises After Hip Arthroscopy: A Video Technique.
AB  - Advanced hip joint-preserving arthroscopic techniques have been shown to improve
      patient-reported functional outcomes with low rates of postoperative
      complications. Prior work has shown that formation of adhesive scar is a
      potential source of persistent pain and cause for revision surgery. As resources
      for postoperative in-studio physical therapy become scarce, a home-based strategy
      to avoid scar formation without adding formal therapy cost may be beneficial. The
      purpose of this technical note is to introduce a patient-centered educational
      video technique for home-caregiver delivery of manual hip pendulum exercises in
      the postoperative setting. This video technique offers access to our method for
      pendulum exercise as part of early recovery after advanced hip arthroscopy.

PMID- 27709056
TI  - Primary Repair of Tibial-Sided Avulsion of the Anterior Cruciate Ligament.
AB  - Lesions of the anterior cruciate ligament (ACL) are common; the current gold
      standard of treatment for such lesions is ACL reconstruction. Tibial-sided soft
      tissue avulsion is a rare subtype of ACL injuries. Unlike femoral-sided ACL
      repair, surgery for acute tibial-sided ACL ruptures has been neither reported nor
      described. This technical note presents a method for primary anatomic ACL
      reinsertion for an acute distal soft-tissue avulsion-type ACL injury, using a
      transosseous pull-out repair technique. Our technique, as an alternative to
      reconstruction, has the potential to enhance healing due to marrow stimulation
      (tibial tunneling). It also preserves the native insertion site and
      proprioceptive function, which may, in turn, reduce the risk of post-traumatic
      osteoarthritis.

PMID- 27709057
TI  - Arthroscopic Iliac Crest Bone Grafting to the Anterior Glenoid.
AB  - Failed arthroscopic soft-tissue stabilization and anterior glenoid bone loss have
      been shown to have high failure rates after standard arthroscopic stabilization
      techniques. For patients with recurrent glenohumeral instability, the Bristow
      Latarjet procedure is currently the standard of care. It is predominantly
      performed through an open deltopectoral approach but has recently been described
      arthroscopically. Although providing excellent clinical outcomes, the Bristow
      Latarjet procedure violates the subscapularis muscle, has a steep learning curve
      with a high complication rate, and permanently changes the anterior shoulder
      anatomy, making any future revision surgery more challenging. We describe a
      technique for arthroscopic anterior glenoid augmentation using iliac crest bone
      graft that does not violate the subscapularis, by creating a far anterior-medial
      portal that traverses superior to the subscapularis and lateral to the conjoint
      tendon. The graft is passed through this portal and secured with rigid fixation.
      An arthroscopic Bankart capsulolabral repair is then performed, making the graft
      extra-articular. A remplissage can easily be added as indicated, allowing this
      procedure to arthroscopically address all 3 major components of structural
      instability: glenoid bone loss, capsulolabral tearing, and humeral bone loss.

PMID- 27709058
TI  - Dry Arthroscopic Single-Stage Cartilage Repair of the Knee Using a Hyaluronic
      Acid-Based Scaffold With Activated Bone Marrow-Derived Mesenchymal Stem Cells.
AB  - Cartilage lesions of the knee are a frequent finding; however, treatment options
      that are capable of restoring hyaline-like tissue are not routinely used. Cell
      based technology such as autologous chondrocyte implantation may in some cases
      provide durable cartilage repair, but availability of this procedure is often
      restricted due to cost constraints. There have been promising outcomes reported
      with the use of scaffolds seeded with activated bone marrow aspirate concentrate
      in cases of chondral injury. There are clear advantages to cell-based cartilage
      repair techniques that are performed as a single-stage procedure, particularly
      when the repair technology can be used in a minimally invasive manner. We present
      an arthroscopic technique of cartilage repair using a hyaluronic acid-based
      scaffold associated with activated bone marrow aspirate concentrate. This
      technique is a cost-effective, minimally invasive, single-stage procedure that
      has the potential for routine use in a wide range of cartilage lesion types and
      locations.

PMID- 27709059
TI  - Medial Opening Wedge Proximal Tibial Osteotomy.
AB  - Genu varus malalignment can lead to medial compartment overload and progression
      of ipsilateral compartment osteoarthritis. To slow this process, a medial opening
      wedge proximal tibial osteotomy (PTO) can be performed. This type of PTO is
      indicated in patients with genu varus malalignment and isolated medial
      compartment osteoarthritis of the knee, prior to or concurrent with medial
      compartment cartilage procedures or meniscal transplants, chronic posterolateral
      corner deficiency, or chronic anterior cruciate ligament deficiency. When
      treating ligamentous instability, a PTO can be performed in isolation, with
      simultaneous ligament reconstruction, or as a staged procedure with the osteotomy
      first, followed by ligament reconstruction if instability persists. Failure to
      address malalignment in cases of concurrent ligament reconstruction leads to
      increased stress on the graft and potential graft failure. One distinct advantage
      of this procedure is the ability to correct deformities in the sagittal and
      coronal planes. The purpose of this article was to describe our technique used to
      perform a medial opening wedge PTO.

PMID- 27709060
TI  - Arthroscopic Juvenile Allograft Cartilage Implantation for Cartilage Lesions of
      the Hip.
AB  - Cartilage lesions in the hip are of high prevalence. Most of these lesions are
      treated with microfracture. Microfracture has relatively good subjective outcomes
      for smaller lesions; however, it is limited by the ability to reproduce hyaline
      cartilage, especially in older patients. For larger chondral defects, we present
      a technique using juvenile allograft cartilage implantation implanted
      arthroscopically to treat cartilage lesions in the hip. The purpose of this
      technical note is to describe the arthroscopic technique for treating chondral
      lesions in the hip with allograft juvenile cartilage.

PMID- 27709061
TI  - Arthroscopic "Panorama" View of the Subacromial Space via Deltoid Fascia Release.
AB  - Proper visualization is of paramount importance during arthroscopic rotator cuff
      repair. We propose a technique that significantly improves the visualization of
      the rotator cuff when viewing from the anterolateral or lateral portals. This
      "panorama" view is obtained by a release of the deep layer of the deltoid fascia,
      which in turn increases the space between the humerus and the deltoid muscle.
      This release increases the volume of the subdeltoid bursa, secondarily increasing
      the field of view of the subacromial space with the camera viewing from the
      anterolateral or lateral portals. This technical note describes a new technique
      useful in obtaining an excellent view of the subacromial space proving very
      useful in both the diagnosis and treatment of rotator cuff pathology.

PMID- 27709062
TI  - Arthroscopic Distal Triceps Repair.
AB  - In this note, we describe an arthroscopic repair of a degenerative tear of the
      triceps using a suture weave and an anatomic footprint anchor. We are able to
      assess, debride, and anatomically repair the distal triceps to its insertion.
      Compared with open procedures, this arthroscopic repair offers lower morbidity,
      faster recovery, and improved cosmesis. Our goal was to improve the function and
      strength of the elbow through this arthroscopic surgical fixation.

PMID- 27709063
TI  - Assessment and Evaluation of Glenoid Bone Loss.
AB  - The preoperative assessment of anterior glenoid bone loss is a critical step in
      surgical planning for patients with recurrent anterior glenohumeral instability.
      The structural integrity of the glenoid has been identified as one of the most
      important factors influencing the success of operative repair. The currently
      accepted gold standard for glenoid structural assessment among most orthopaedic
      surgeons is the use of 3-dimensional reconstructed computed tomography images
      with the humeral head digitally subtracted, yielding an en face sagittal oblique
      view of the glenoid. This view allows for evaluation of glenoid morphology and
      quantitative assessment of glenoid bone loss. In this article, we describe the
      practical application of ImageJ software (National Institutes of Health,
      Bethesda, MD) to quantify the amount of glenoid bone loss reported as a
      percentage of either total surface area or diameter. The following equations are
      used in this technical note for the diameter-based method and surface area
      method, respectively: Percent bone loss = (Defect width/Diameter of inferior
      glenoid circle) * 100% and Percent bone loss = (Defect surface area/Surface area
      of inferior glenoid circle) * 100%.

PMID- 27709064
TI  - Loffler syndrome on a Louisiana pig farm.
AB  - Loffler syndrome, a fulminant eosinophilic pneumonitis associated with the larval
      migratory phase of human parasites, is rarely reported in the United States. A
      previously healthy 8-year-old male was hospitalized with tachypnea, cough,
      hypoxemia, and fever of one week's duration. History revealed exposure to pigs on
      his family's farm in southernmost Louisiana, where the patient was responsible
      for cleaning the farm's pigpens. His fingernails were soiled and extremely short,
      with the edge of the nail bed exposed secondary to onychophagia. Laboratory
      evaluation demonstrated peripheral eosinophilia (39%), pulmonary eosinophilia
      (86%), high total IgE, diffuse reticulonodular lung opacities, and mixed
      obstructive and restrictive pulmonary function pattern. Systemic corticosteroids
      were initiated for his acute respiratory insufficiency and produced rapid
      clinical improvement. Serum Ascaris-specific IgE was markedly elevated and he was
      treated with albendazole. An extensive evaluation for other infectious and
      allergic etiologies was negative. A site visit to the family farm and laboratory
      investigation was coordinated with the Louisiana Animal Disease Diagnostic
      Laboratory at LSU. Ascaris suum eggs were detected in fresh pig feces and in the
      soil immediately surrounding the pens. Ascariasis should be considered even in
      the absence of travel history, especially in swine raising areas that are endemic
      for Ascaris in pigs, such as the southeastern United States. Onychophagia is a
      highly probable mechanism of zoonotic fecal-oral transmission in this case, and
      such habits could lead to continual reinfection. Systemic corticosteroids were
      effective in treating the patient's acute respiratory compromise due to Loffler
      syndrome.

PMID- 27709068
TI  - Bquant - Novel script for batch quantification of LCMS data.
AB  - Quantitative target analysis by liquid chromatography coupled to mass
      spectrometry (LCMS) is ubiquitous in environmental, metabolomic and toxicological
      studies. Targeted LCMS methods are capable of the simultaneous determination of
      literally hundreds of analytes. Although acquiring of instrumental data is very
      fast, data post-processing i.e. quantification can be time consuming step (and)or
      dependent to various commercial software packages. In attempt to facilitate this
      drawback Wolfram Mathematica script for batch quantification of LCMS data was
      created. Script works with direct outputs of integration algorithms created by
      different instrument control software's or custom created outputs. Key benefits
      of Bquant script are: *simple and automated routine for batch mode
      quantification*vast improvement in processing time (especially compared to manual
      interpretation)*data can be quickly re-analysed using different inputs Script was
      validated on various datasets and some of these were provided as working
      examples.

PMID- 27709065
TI  - Low putamen activity associated with poor reward sensitivity in childhood chronic
      fatigue syndrome.
AB  - Motivational signals influence a wide variety of cognitive processes and
      components of behavioral performance. Cognitive dysfunction in patients with
      childhood chronic fatigue syndrome (CCFS) may be closely associated with a low
      motivation to learn induced by impaired neural reward processing. However, the
      extent to which reward processing is impaired in CCFS patients is unclear. The
      aim of the present functional magnetic resonance imaging (fMRI) study was to
      determine whether brain activity in regions related to reward sensitivity is
      impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean
      age, 13.6 +/- 1.0 years) and 13 healthy children and adolescents (HCA) (mean age,
      13.7 +/- 1.3 years) performing a monetary reward task. Neural activity in high-
      and low-monetary-reward conditions was compared between CCFS and HCA groups.
      Severity of fatigue and the reward obtained from learning in daily life were
      evaluated by questionnaires. Activity of the putamen was lower in the CCFS group
      than in the HCA group in the low-reward condition, but not in the high-reward
      condition. Activity of the putamen in the low-reward condition in CCFS patients
      was negatively and positively correlated with severity of fatigue and the reward
      from learning in daily life, respectively. We previously revealed that motivation
      to learn was correlated with striatal activity, particularly the neural activity
      in the putamen. This suggests that in CCFS patients low putamen activity,
      associated with altered dopaminergic function, decreases reward sensitivity and
      lowers motivation to learn.

PMID- 27709067
TI  - Helminth community structure in two species of arctic-breeding waterfowl.
AB  - Climate change is occurring rapidly at high latitudes, and subsequent changes in
      parasite communities may have implications for hosts including wildlife and
      humans. Waterfowl, in particular, harbor numerous parasites and may facilitate
      parasite movement across broad geographic areas due to migratory movements.
      However, little is known about helminth community structure of waterfowl at
      northern latitudes. We investigated the helminth communities of two avian
      herbivores that breed at high latitudes, Pacific black brant (Branta bernicla
      nigricans), and greater white-fronted geese (Anser albifrons), to examine effects
      of species, geographic area, age, and sex on helminth species richness,
      aggregation, prevalence, and intensity. We collected 83 and 58 black brant and
      white-fronted geese, respectively, from Arctic and Subarctic Alaska July-August
      2014. We identified 10 known helminth species (Amidostomum anseris, Amidostomum
      spatulatum, Drepanidotaenia lanceolata, Epomidiostomum crami, Heterakis dispar,
      Notocotylus attenuatus, Tetrameres striata, Trichostrongylus tenuis,
      Tschertkovilepis setigera, and Wardoides nyrocae) and 1 previously undescribed
      trematode. All geese sampled were infected with at least one helminth species.
      All helminth species identified were present in both age classes and species,
      providing evidence of transmission at high latitudes and suggesting broad host
      susceptibility. Also, all but one helminth species were present at both sites,
      suggesting conditions are suitable for transmission across a large
      latitudinal/environmental gradient. Our study provides important baseline
      information on avian parasites that can be used to evaluate the effects of a
      changing climate on host-parasite distributions.

PMID- 27709069
TI  - 7th Union Europe Conference on Lung Health, 22-24 June 2016, Bratislava
      (Slovakia): a delegate report.

PMID- 27709066
TI  - Brain volume loss contributes to arousal and empathy dysregulation following
      severe traumatic brain injury.
AB  - Severe traumatic brain injury (TBI) often leads to deficits in physiological
      arousal and empathy, which are thought to be linked. This study examined whether
      injury-related brain volume loss in key limbic system structures is associated
      with these deficits. Twenty-four adults with TBI and 24 matched Controls
      underwent MRI scans to establish grey matter volumes in the amygdala, thalamus,
      and hippocampus. EEG and skin conductance levels were recorded to index basal
      physiological arousal. Self-report emotional empathy levels were also assessed.
      The TBI group had reduced brain volumes, topographic alpha differences, and lower
      emotional empathy compared to Controls. Regional brain volumes were
      differentially correlated to arousal and self-report empathy. Importantly, lower
      volume in pertinent brain structures correlated with lower empathy, for
      participants with and without TBI. Overall we provide new insights into empathic
      processes after TBI and their relationship to brain volume loss.

PMID- 27709070
TI  - Endovascular stent placement for chronic post-thrombotic symptomatic ilio-femoral
      venous obstructive lesions: a single-center study of safety, efficacy and quality
      of-life improvement.
AB  - BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent complication of deep
      vein thrombosis (DVT) despite adequate treatment. Venous angioplasty and stent
      placement has been progressively used to restore and maintain venous patency in
      PTS patients. This study reports our single-center experience with the use of
      endovascular treatment for chronic post-thrombotic symptomatic ilio-femoral
      venous obstructive lesions. METHODS: A prospective mono-centric observational
      cohort study of PTS patients with chronic symptomatic ilio-femoral venous
      obstructive lesions referred for endovascular treatment was conducted from March
      2012 to April 2016. Procedure consisted in recanalization, pre-dilation and self
      expandable stenting of stenotic or occluded iliac and/or femoral veins. Severity
      of PTS, quality-of-life and treatment outcomes were assessed using Villalta scale
      and Chronic Venous Insufficiency Questionnaire (CIVIQ-20) at baseline and 3
      months after the procedure. Imaging follow-up was based on duplex ultrasound (US)
      and computed tomography (CT). RESULTS: Twenty-one patients (11 females, 10 males;
      median age, 41 years; range, 32-60) were included. Recanalization and stenting
      was successfully accomplished in all prime procedures, 4 patients benefitted from
      an additional procedure. Immediate technical success rate was 96% considering 25
      procedures, performed without any complications. Median follow-up was 18 months
      (range, 6-30 months) with a 90.5% stent patency rate. Villalta score
      significantly decreased from baseline compared with 3 months after the procedure
      [14 (range, 11-22) and 5 (range, 1-10), respectively, P<0.0001], showing a
      significant decrease in the severity of PTS. CIVIQ-20 score significantly
      decreased from baseline compared with 3 months after stenting [48.5 (range, 39
      73) and 26.5 (range, 21-45), respectively, P<0.0001] thus showing a significant
      improvement of quality-of-life. Post-procedural CIVIQ-20 score was significantly
      associated with Villalta score (95% CI, 1.53-2.95; P<0.0001). CONCLUSIONS: Our
      results confirm the high clinical success rate and safety of endovascular PTS
      treatment and highlight the significant impact of stenting on the quality of life
      of patients with chronic symptomatic ilio-femoral venous obstructive lesions.

PMID- 27709071
TI  - Black blood T1rho MR imaging may diagnose early stage liver fibrosis: a proof-of
      principle study with rat biliary duct ligation model.
AB  - BACKGROUND: To explore black blood T1rho (T1rho) liver imaging and investigate
      the earliest stage when biliary duct ligation (BDL) induced liver fibrosis can be
      diagnosed. METHODS: MR was performed at 3 Tesla. A T1rho prepared 2D fast spin
      echo (FSE) sequence with acquisition of four spin lock times (TSLs: 1, 10, 30,
      and 50 msec) and spin-lock frequency of 500 Hz was applied. Inherent black blood
      effect of FSE and double inversion recovery (DIR) achieved blood signal
      suppression, and 3 axial sections per liver were obtained. Male Sprague-Dawley
      rats were scanned at baseline (n=32), and on day-3 (n=13), day-5 (n=11), day-7
      (n=10), day-10 (n=4) respectively after BDL. Hematoxylin-eosin (HE) and
      picrosirius red staining liver histology was obtained at these time points.
      RESULTS: The physiological liver parenchyma T1rho was 38.38+/-1.53 msec (range,
      36.05-41.53 msec). Liver T1rho value elevated progressively after BDL. On day-10
      after BDL all experimental animals can be separated from normal liver based on
      T1rho measurement with lowest value being 42.82 msec. Day-7 and day-10 liver
      resembled METAVIR stage-F1/F2 fibrosis, and fibrous area counted for 0.22%+/
      0.13% and 0.38%+/-0.44% of liver parenchyma area, respectively. CONCLUSIONS: This
      study provides the first proof-of-principle that T1rho might diagnose early stage
      liver fibrosis.

PMID- 27709072
TI  - Hirayama's disease: an Italian single center experience and review of the
      literature.
AB  - BACKGROUND: Hirayama's disease (HD), is a benign, self-limited, motor neuron
      disease, characterized by asymmetric weakness and atrophy of one or both distal
      upper extremities. In the present study we report the clinical,
      electrophysiological and MRI features of a group of Italian patients, with review
      of the literature. Moreover we propose an optimized MRI protocol for patients
      with suspected or diagnosed HD in order to make an early diagnosis and a
      standardized follow up. METHODS: Eight patients with clinical suspicion of
      Hirayama disease underwent evaluation between January 2007 and November 2013. All
      patients underwent standard nerve conduction studies (NCS), electromyography
      (EMG) and motor/sensory evoked potentials (MEP/SEP). Cervical spine MRI studies
      were conducted with a 1.5 Tesla MRI scanner in neutral and flexion position,
      including sagittal T1-weighted sequences and sagittal and axial T2-weighted
      sequences. The following diagnostic features were evaluated: abnormal cervical
      curvature, localized cervical cord atrophy in the lower tract (C4-C7), presence
      of cord flattening (CF), intramedullary signal hyperintensity on T2 weighted
      sequences, anterior shifting of the posterior wall of the cervical dural sac
      (ASD) and presence of flow voids (EFV) in the posterior epidural space during
      flexion. RESULTS: All patients complained of weakness in hand muscles as initial
      symptoms, associated with hand tremor in three of them and abnormal sweating of
      the hand palm in two of them. No sensory deficits and weakness at lower limbs
      were reported by any patients. Distal deep tendon reflexes at upper limbs were
      absent in all patients with the absence of the right tricipital reflex in one of
      them. Deep tendon reflexes at lower limbs were normal and no signs of pyramidal
      tract involvement were present. The clinical involvement at onset was unilateral
      in six patients (three left-sided and three right-sided) and bilateral asymmetric
      in two of them, with the right side more affected. With the progression of the
      disease all patients but one experienced weakness and wasting of hand muscles and
      forearm bilaterally, but still asymmetric. The duration of the progression phase
      of the disease ranged from eight months to three years. In all patients, NCS and
      EMG findings were consistent with a spinal metameric disorder involving the C7-T1
      myotomes bilaterally; sensory conduction and electrophysiologic features at lower
      limbs were normal. MEP and SEP were normal and we did not observe the
      disappearance of the spinal potential during the neck flexion in any of the
      patients. MRI is the best diagnostic tool in the diagnosis of HD; it can confirm
      clinical diagnosis and exclude other conditions responsible for the neurological
      deficits leading to a correct patient management and therapy, limiting arm
      impairment. On MRI all patients had loss of the normal cervical lordosis (100%).
      Five patients had loss of attachment of posterior dural sac and anterior dural
      shift on flexion MRI with presence of flow voids from venous plexus congestion
      (62.5%); three patients had no anterior dislocation of the dural sac and no
      epidural vein congestion. Two patients showed localized cord atrophy, one at C5
      C6 and the other at C6-C7 level (25%). Three patients had T2 intramedullary
      hyperintensities (37.5%) and cord flattening (CF) was present in 5 patients of 8
      (62.5%). CONCLUSIONS: HD is a rare entity and a self-limited condition, but it
      has to be early differentiated from other diseases that may determine myelopathy
      and amyotrophy to establish a correct therapy and limit arm impairment. MRI is
      very important to confirm the clinical suspect of HD and a standardized MRI
      protocol using axial and sagittal images in both neutral and flexing position is
      needed, in order to diagnose and follow up affected patients.

PMID- 27709073
TI  - Effects of magnetic field strength and b value on the sensitivity and specificity
      of quantitative breast diffusion-weighted MRI.
AB  - BACKGROUND: To evaluate the effect of b value or the magnetic field strength (B0)
      on the sensitivity and specificity of quantitative breast diffusion-weighted
      imaging (DWI). METHODS: A total of 126 patients underwent clinical breast MRI
      that included pre-contrast DWI imaging using b values of both 1,000 and 1,500
      s/mm2 at either 1.5 T (n=86) or 3.0 T (n=40). Quantitative apparent diffusion
      coefficients (ADC) were measured and compared for 18 benign, 33 malignant
      lesions, and 126 normal breast tissues. Optimal ADCmean threshold for
      differentiating benign and malignant lesions was estimated and the effect of b
      values and B0 were examined using a generalized estimating equations (GEE) model.
      RESULTS: The optimal ADCmean threshold was 1.235*10-3 mm2/s for b value of 1,000
      and 0.934*10-3 mm2/s for b value of 1,500. Using these thresholds, the
      sensitivities and specificities were 96% and 89% (b value =1,000, B0 =1.5 T), 89%
      and 98% (b value =1,000, B0 =3.0 T), 88% and 96% (b value =1,500, B0 =1.5 T), and
      67% and 100% (b value =1,500, B0 =3.0 T). No significant difference was found
      between different B0 (P=0.26) or b values (P=0.28). CONCLUSIONS: Better
      sensitivity is achieved with DWI of b value =1,000 than with b value =1,500.
      However, b value and B0 do not significantly impact diagnostic performance of DWI
      when using appropriate thresholds.

PMID- 27709074
TI  - Correlation of delta high-resolution computed tomography (HRCT) score with delta
      clinical variables in early systemic sclerosis (SSc) patients.
AB  - BACKGROUND: The correlation of changes (delta: Delta) of high-resolution computed
      tomography (HRCT) score with the Delta of other clinical variables has not been
      well studied. The purpose of this study was to determine the correlation of Delta
      HRCT score with Delta percent predicted forced vital capacity (%pFVC), Delta
      modified Rodnan Skin Score (mRSS), Delta erythrocyte sedimentation rate (ESR),
      and Delta percent of oxygen saturation at room air (%SpO2) in patients with early
      systemic sclerosis (SSc). METHODS: We used an inception cohort of early-SSc
      patients seen at the Rheumatology Clinic, Chiang Mai University, Thailand,
      between January 2010 and June 2014. All patients underwent HRCT at study entry
      and every 12 months thereafter. Thirty-one SSc patients who underwent pulmonary
      function test (PFT) within 12 weeks of their corresponding HRCT at baseline and
      last visit were identified. The extent of ground glass (GG), lung fibrosis (Fib),
      bronchiectasis (B), and honeycombing (HC) was scored, and then aggregated to
      produce a total (t) HRCT score. RESULTS: Mean +/- SD age and disease duration
      from non-Raynaud's phenomenon (NRP) to undergo HRCT at baseline were 52.2+/-8.8
      years and 11.7+/-7.1 months, respectively. Seventeen (54.8%) patients were female
      and 20 (64.5%) were classified as dcSSc. The mean +/- SD interval between the two
      HRCT tests was 16.0+/-7.2 months. The Delta HRCT scores [total fibrosis scores (t
      Fib), total bronchiectasis scores (t-B), and total HRCT score (t-HRCT) scores]
      and Delta mRSS, but not Delta %pFVC, showed significant change over the
      observation period. We found significant correlation of Delta total honeycombing
      scores (t-HC) with Delta ESR (r=-0.44, P<0.05), and Delta t-Fib with Delta %SpO2
      (r=-0.38, P<0.05). However, no significant correlation of any Delta HRCT scores
      with Delta %pFVC and Delta mRSS were observed. CONCLUSIONS: In this study, the
      changes in the HRCT scores were greater than %pFVC; this, along with their
      correlations with the changes in ESR and %SpO2, suggest that HRCT scores are a
      useful and sensitive method for monitoring disease progression in early SSc
      related ILD (SSc-ILD).

PMID- 27709075
TI  - Automated registration and enhanced processing of clinical optical coherence
      tomography angiography.
AB  - BACKGROUND: Motion artifacts degrade the quality of optical coherence tomography
      angiography (OCTA). Orthogonal registration can eliminate the majority of these
      artifacts, but some artifacts persist in most clinical images. We evaluate an
      automated registration algorithm with selective merging and filtering to remove
      remaining artifacts and improve the quality of images. METHODS: A 70 kHz
      commercial spectral domain OCT was used to obtain 3 mm * 3 mm OCTA in 10 healthy,
      5 age-related macular degeneration (AMD), and 31 diabetic retinopathy (DR)
      participants. Projection artifacts were removed and images were segmented into 3
      inner retinal plexuses. Amplitude thresholding identified lines containing a
      residual artifact and correlation between neighboring lines identified distorted
      stripes. Then the angiograms were registered and the lines selectively merged. A
      vesselness filter was applied to the resulting images. The images were evaluated
      for signal-to-noise ratio (SNR), image entropy, vessel connectivity and vessel
      density. RESULTS: Registration and selective merging (RSM) algorithm improved the
      SNR (P<0.02) compared to orthogonal registration alone. RSM with vesselness
      filter increased the image entropy (P<10-8) and reduced inter-subject variability
      (standard error <=3%, n=10) in healthy eyes. The method improved vessel details
      and connectivity in OCTA of healthy, DR and neovascular AMD eyes. CONCLUSIONS:
      This automated registration method eliminates residual motion artifacts and
      enhances the visualization of vessels in OCTA.

PMID- 27709076
TI  - Lumbar intervertebral discs T2 relaxometry and T1rho relaxometry correlation with
      age in asymptomatic young adults.
AB  - BACKGROUND: To investigate the detection of intervertebral disc (IVD) composition
      aging-related changes using T2 and T1rho relaxometry in vivo in asymptomatic
      young adults. METHODS: We recruited ninety asymptomatic and young adults (42 men
      and 48 women) between 20 and 40 years old. T2 and T1rho lumbar spine mappings
      were acquired using 1.5 T magnetic resonance imaging (MRI) scanner. Two
      independent observers manually segmented 450 lumbar discs in all slices. They
      also performed sub region segmentation of annulus fibrosus (AF) and nucleus
      pulposus (NP) at the central MRI sagittal slices. RESULTS: There was no
      difference between men and women for T2 (P=0.37) or T1rho relaxometry (P=0.97).
      There was a negative correlation between age (20-40 years) and IVD T2 relaxation
      time of the whole disc (r=-0.30, P<0.0001), NP (r=-0.20 to -0.51, P<0.05) and
      posterior AF (r=-0.21 to -0.31, P<0.05) at all lumbar disc levels. There was no
      statistical correlation between aging and IVD T1rho relaxation both for NP and
      AF. CONCLUSIONS: T2 relaxometry detected gradual IVD dehydration in the first two
      decades of adulthood. We observed no significant variation of T1rho or volumetry
      with aging in our study group. Our results suggest that T2 mapping may be more
      appropriate to detect early IVD aging changes.

PMID- 27709077
TI  - Correlation between pneumonitis risk in radiation oncology and lung density
      measured with X-ray computed tomography.
AB  - BACKGROUND: The risk of toxicity with radiation oncology for lung cancer limits
      the maximal radiation dose that can be delivered to thoracic tumors. This study
      aims at investigating the correlation between normal tissue complication
      probability (NTCP) and physical lung density by analyzing the computed tomography
      (CT) scan imaging used for radiotherapy dose planning. METHODS: Data from CT of
      lung cancer patients (n=10), treated with three dimensional radiotherapy, were
      selected for this study. The dose was calculated using analytical anisotropic
      algorithm (AAA). Dose volume histograms (DVH) for healthy lung (lung excluding
      targets) were calculated. The NTCP for lung radiation induced pneumonitis was
      computed using initial radiobiological parameters from Lyman-Kutcher and Burman
      (LKB) model and readjusted parameters for AAA, with alpha/beta=3. The correlation
      coefficient "rho" was calculated using Spearman's rank test. The bootstrap method
      was used to estimate the 95% confidence interval (95% CI). Wilcoxon paired test
      was used to calculate P values. RESULTS: Bootstrapping simulation revealed
      significant difference between NTCP computed with the initial radiobiological
      parameters and that computed with the parameters readjusted for AAA (P=0.03). The
      results of simulations based on 1,000 replications showed no correlation for NTCP
      with density, with "rho" <0.3. CONCLUSIONS: For a given set of patients, we
      assessed the correlation between NTCP and lung density using bootstrap analysis.
      The lack of correlation could result either from a very accurate dose
      calculation, by AAA, whatever the lung density yielding a NTCP result only
      dependant of the dose and not any more of the density; or to the very limited
      range of natural variation of relative electronic density (0.15 to 0.20) observed
      in this small series of patients. Another important parameter is the bootstrap
      simulation with 1,000 random samplings may have underestimated the correlation,
      since the initial data (n=10) showed a weak correlation.

PMID- 27709078
TI  - Statistical assessment of bi-exponential diffusion weighted imaging signal
      characteristics induced by intravoxel incoherent motion in malignant breast
      tumors.
AB  - BACKGROUND: The purpose of this study is to statistically assess whether bi
      exponential intravoxel incoherent motion (IVIM) model better characterizes
      diffusion weighted imaging (DWI) signal of malignant breast tumor than mono
      exponential Gaussian diffusion model. METHODS: 3 T DWI data of 29 malignant
      breast tumors were retrospectively included. Linear least-square mono-exponential
      fitting and segmented least-square bi-exponential fitting were used for apparent
      diffusion coefficient (ADC) and IVIM parameter quantification, respectively. F
      test and Akaike Information Criterion (AIC) were used to statistically assess the
      preference of mono-exponential and bi-exponential model using region-of-interests
      (ROI)-averaged and voxel-wise analysis. RESULTS: For ROI-averaged analysis, 15
      tumors were significantly better fitted by bi-exponential function and 14 tumors
      exhibited mono-exponential behavior. The calculated ADC, D (true diffusion
      coefficient) and f (pseudo-diffusion fraction) showed no significant differences
      between mono-exponential and bi-exponential preferable tumors. Voxel-wise
      analysis revealed that 27 tumors contained more voxels exhibiting mono
      exponential DWI decay while only 2 tumors presented more bi-exponential decay
      voxels. ADC was consistently and significantly larger than D for both ROI
      averaged and voxel-wise analysis. CONCLUSIONS: Although the presence of IVIM
      effect in malignant breast tumors could be suggested, statistical assessment
      shows that bi-exponential fitting does not necessarily better represent the DWI
      signal decay in breast cancer under clinically typical acquisition protocol and
      signal-to-noise ratio (SNR). Our study indicates the importance to statistically
      examine the breast cancer DWI signal characteristics in practice.

PMID- 27709080
TI  - Idiopathic heterotopic ossification of bilateral subscapularis tendons:
      illustration of a rare entity and a concise literature review.
AB  - Ossification of the subscapularis tendon is an extremely uncommon, poorly
      described lesion with little known about its etiopathogenesis and clinical
      significance. To the best of our knowledge, only three cases of this entity have
      been reported till now, which were all unilateral. The authors present first case
      of ossification of bilateral subscapularis tendons in a 57-year-old male and hope
      that with increase in the number of reported cases, proper guidelines for
      management of such cases can be formulated.

PMID- 27709081
TI  - Parascapular mass revealing primary tuberculosis of the posterior arch.
AB  - We report the case of a parascapular abscess revealing primary tuberculosis of
      the posterior arch in a 31-year-old man. Sectional imaging is essential in order
      to detect the different lesions of this atypical spinal tuberculosis as
      osteolysis of the posterior arch extendible to vertebral body, osteocondensation,
      epidural extension which is common in this location, and high specificity of a
      zygapophysial, costo-vertebral or transverse arthritis.

PMID- 27709082
TI  - A rare case of facial neurofibroma.

PMID- 27709083
TI  - Combined computed tomography (CT)/scintigraphy strategy may help in diagnostic
      dilemmas in interstitial lung disease (ILD).

PMID- 27709079
TI  - Functional magnetic resonance imaging techniques and their development for
      radiation therapy planning and monitoring in the head and neck cancers.
AB  - Radiation therapy (RT), in particular intensity-modulated radiation therapy
      (IMRT), is becoming a more important nonsurgical treatment strategy in head and
      neck cancer (HNC). The further development of IMRT imposes more critical
      requirements on clinical imaging, and these requirements cannot be fully
      fulfilled by the existing radiotherapeutic imaging workhorse of X-ray based
      imaging methods. Magnetic resonance imaging (MRI) has increasingly gained more
      interests from radiation oncology community and holds great potential for RT
      applications, mainly due to its non-ionizing radiation nature and superior soft
      tissue image contrast. Beyond anatomical imaging, MRI provides a variety of
      functional imaging techniques to investigate the functionality and metabolism of
      living tissue. The major purpose of this paper is to give a concise and timely
      review of some advanced functional MRI techniques that may potentially benefit
      conformal, tailored and adaptive RT in the HNC. The basic principle of each
      functional MRI technique is briefly introduced and their use in RT of HNC is
      described. Limitation and future development of these functional MRI techniques
      for HNC radiotherapeutic applications are discussed. More rigorous studies are
      warranted to translate the hypotheses into credible evidences in order to
      establish the role of functional MRI in the clinical practice of head and neck
      radiation oncology.

PMID- 27709084
TI  - Scientific papers presented orally at radiology meetings-trends in subspecialty
      publication rates and adaptations associated with the highest impact factor
      journal publications.

PMID- 27709085
TI  - Bilateral renal lymphangiectasia-an unusual cause of abdominal distension and
      flank pain in a child.

PMID- 27709086
TI  - A large heterotopic ossification in a 25 years old laparotomy scar.

PMID- 27709087
TI  - Towards consistency for magnetic resonance (MR) relaxometry of lumbar
      intervertebral discs.

PMID- 27709088
TI  - An unusual cause of back pain in a child: spinal subdural haematoma secondary to
      intracranial arachnoid cyst haemorrhage.

PMID- 27709089
TI  - Magnetic resonance enterography findings of a gastrocolic fistula in Crohn's
      disease.

PMID- 27709090
TI  - Advances and research in congenital heart disease.

PMID- 27709091
TI  - The battleground of the stenotic branch pulmonary arteries: the surgical approach
      of "less is more".

PMID- 27709093
TI  - How to set-up a program of minimally-invasive surgery for congenital heart
      defects.
AB  - BACKGROUND: Mid-line sternotomy is the commonest incision for cardiac surgery.
      Alternative approaches are becoming fashionable in many centres, amidst some
      reluctance because of learning curves and overall complexity. Our recent
      experience in starting a new program on minimally invasive pediatric cardiac
      surgery is presented. The rationale for a stepwise onset and the short-medium
      term results for a three-year span are displayed. METHODS: A three-step schedule
      is planned: First, an experienced surgeon (A) starts performing simple cases.
      Second, new surgeons (B, C, D, E) are introduced to the minimally invasive
      techniques according to their own proficiency and skills. Third, the new adopters
      are enhanced to suggest and develop further minimally invasive approaches. Two
      quality markers are defined: conversion rate and complications. RESULTS: In part
      one, surgeon A performs sub-mammary, axillary and lower mini-sternotomy
      approaches for simple cardiac defects. In part two, surgeons B, C, D and E are
      customly introduced to such incisions. In part three, new approaches such as
      upper mini-sternotomy, postero-lateral thoracotomy and video-assisted mini
      thoracotomy are introduced after being suggested and developed by surgeons B, C
      and E, as well as an algorithm to match cardiac conditions and age/weight to a
      given alternative approach. The conversion rate is one out of 148 patients. Two
      major complications were recorded, none of them related to our alternative
      approach. Four minor complications linked to the new incision were registered.
      The minimally invasive to mid-line sternotomy ratio rose from 20% in the first
      year to 40% in the third year. CONCLUSIONS: Minimally invasive pediatric cardiac
      surgery is becoming a common procedure worldwide. Our schedule to set up a
      program proves beneficial. The three-step approach has been successful in our
      experience, allowing a tailored training for every new surgeon and enhancing the
      enthusiasm in developing further strategies on their own. Recording conversion
      rates and complications stands for quality standards. A twofold increase in
      minimally invasive procedures was observed in two years. The short-medium term
      results after three years are excellent.

PMID- 27709092
TI  - Antegrade cerebral perfusion at 25  degrees C for arch reconstruction in newborns
      and children preserves perioperative cerebral oxygenation and serum creatinine.
AB  - BACKGROUND: Antegrade cerebral perfusion (ACP) typically is used with deep
      hypothermia for cerebral protection during aortic arch reconstructions. The
      impact of ACP on cerebral oxygenation and serum creatinine at a more tepid 25 
      degrees C was studied in newborns and children. METHODS: Between 2010 and 2014,
      61 newborns and children (<5 years old) underwent aortic arch reconstruction
      using moderate hypothermia (25.0+/-0.9  degrees C) with ACP and a pH-stat blood
      gas management strategy. These included 44% Norwood-type operations, 30% isolated
      arch reconstructions, and 26% arch reconstructions with other major procedures.
      Median patient age at surgery was 9 days (range, 3 days-4.7 years). Cerebral
      oxygenation (NIRS) was monitored continuously perioperatively for 120 hours.
      Serum creatinine was monitored daily. RESULTS: Median cardiopulmonary bypass
      (CPB) and cross clamp times were 181 minutes (range, 82-652 minutes) and 72
      minutes (range, 10-364 minutes), respectively. ACP was performed at a mean flow
      rate of 46+/-6 mL/min/kg for a median of 48 minutes (range, 10-123 minutes).
      Cerebral and somatic NIRS were preserved intraoperatively and remained at
      baseline postoperatively during the first 120 hours. Peak postoperative serum
      creatinine levels averaged 0.7+/-0.3 mg/dL for all patients. There were 4 (6.6%)
      discharge mortalities. Six patients (9.8%) required ECMO support. Median
      postoperative length of hospital and intensive care unit (ICU) stay were 16
      days(range, 4-104 days) and 9 days (range, 1-104 days), respectively. Two
      patients (3.3%) received short-term peritoneal dialysis for fluid removal, and
      none required hemodialysis. Three patients (4.9%) had an isolated seizure which
      resolved with medical therapy, and none had a neurologic deficit or stroke.
      CONCLUSIONS: ACP at 25  degrees C preserved perioperative cerebral oxygenation
      and serum creatinine for newborns and children undergoing arch reconstruction.
      Early outcomes are encouraging, and additional study is warranted to assess the
      impact on late outcomes.

PMID- 27709094
TI  - Goal-directed-perfusion in neonatal aortic arch surgery.
AB  - Reduction of mortality and morbidity in congenital cardiac surgery has always
      been and remains a major target for the complete team involved. As operative
      techniques are more and more standardized and refined, surgical risk and
      associated complication rates have constantly been reduced to an acceptable level
      but are both still present. Aortic arch surgery in neonates seems to be of
      particular interest, because perfusion techniques differ widely among
      institutions and an ideal form of a so called "total body perfusion (TBP)" is
      somewhat difficult to achieve. Thus concepts of deep hypothermic circulatory
      arrest (DHCA), regional cerebral perfusion (RCP/with cardioplegic cardiac arrest
      or on the perfused beating heart) and TBP exist in parallel and all carry an
      individual risk for organ damage related to perfusion management, chosen core
      temperature and time on bypass. Patient safety relies more and more on adequate
      end organ perfusion on cardiopulmonary bypass, especially sensitive organs like
      the brain, heart, kidney, liver and the gut, whereby on adequate tissue
      protection, temperature management and oxygen delivery should be visualized and
      monitored.

PMID- 27709095
TI  - Hypoplastic left heart syndrome: current perspectives.
AB  - Since the first successful intervention for hypoplastic left heart syndrome
      (HLHS) was undertaken by Norwood in 1983, there have been many advancements in
      the pre-, intra-, and postoperative care of these children for a diagnosis that
      just 25 years ago was almost certainly a fatal one. This paper aims to describe
      the most recent trends and perspectives on the treatment of HLHS. In particular,
      we will discuss the five current options for HLHS, including Norwood stage I as
      the beginning to 3-stage palliation, transplant, true hybrid, hybrid-bridge-to
      Norwood, and compassionate care.

PMID- 27709097
TI  - Critical cardiac care in children: looking backward and looking forward.
AB  - The growth of Pediatric Cardiovascular Intensive Care as a subspecialty has been
      incredible. Outcomes have improved, care delivery has matured, and research has
      made advances. Within this review, we take the opportunity to examine the
      subspecialty's past accomplishments with pride, take stock in its current state,
      and look forward with excitement to its future. While outcomes in general have
      improved dramatically, we must always be aware of the outcomes that matter to
      families and patients. Additionally, we must constantly ask ourselves to improve.
      Research into neuroprotection and individual therapeutic strategies based in
      genomic medicine provide the next opportunity for the subspecialty to improve.

PMID- 27709096
TI  - Prophylactic arrhythmia surgery in association with congenital heart disease.
AB  - Certain congenital heart anomalies make patients more susceptible to arrhythmia
      development throughout their lives. This poses the question whether prophylactic
      arrhythmia surgery should be incorporated into reparative open heart procedures
      for congenital heart disease. There is currently no consensus on what constitutes
      a standard prophylactic procedure, owing to the questions that remain regarding
      lesions to be performed; energy sources to use; proximity of energy source or
      incisions to coronary arteries, sinoatrial node, atrioventricular node;
      circumstances for right atrial, left atrial, or biatrial appendectomy; and
      whether to perform a right, left, or biatrial maze procedure. These
      considerations are important because prophylactic arrhythmia procedures are
      performed without knowing if the patient will actually develop an arrhythmia in
      his or her lifetime. By reviewing and summarizing the literature, congenital
      heart disease patients who are at risk for developing atrial arrhythmias can be
      identified and lesion sets can be suggested in an effort to standardize
      experimental protocols for prophylactic arrhythmia surgery.

PMID- 27709098
TI  - Reverse Szabo technique for stenting a single major aorto-pulmonary collateral
      vessel in pulmonary atresia with ventricular septal defect.
AB  - Management of pulmonary atresia with ventricular septal defect (PA-VSD) in the
      neonatal period presents numerous challenges. Endovascular stenting of the ductus
      arteriosus or of a collateral vessel in ductal-dependent pulmonary circulation as
      an alternative to the Blalock-Taussig (BT) shunt has become increasingly popular
      in the last decades. The utilization of the reverse Szabo (anchor-wire) technique
      for single collateral vessel stenting in a case of PA-VSD is described.

PMID- 27709099
TI  - Preoperative evaluation and surgical decision-making in pediatric epilepsy
      surgery.
AB  - Epilepsy is a common disease in the pediatric population, and the majority of
      cases are controlled with medications and lifestyle modification. For the
      children whose seizures are pharmacoresistant, continued epileptic activity can
      have a severely detrimental impact on cognitive development. Early referral of
      children with drug-resistant seizures to a pediatric epilepsy surgery center for
      evaluation is critical to achieving optimal patient outcomes. There are several
      components to a thorough presurgical evaluation, including a detailed medical
      history and physical examination, noninvasive testing including
      electroencephalogram, magnetic resonance imaging (MRI) of the brain, and often
      metabolic imaging. When necessary, invasive diagnostic testing using intracranial
      monitoring can be used. The identification of an epileptic focus may allow
      resection or disconnection from normal brain structures, with the ultimate goal
      of complete seizure remission. Additional operative measures can decrease seizure
      frequency and/or intensity if a clear epileptic focus cannot be identified. In
      this review, we will discuss the nuances of presurgical evaluation and decision
      making in the management of children with drug-resistant epilepsy (DRE).

PMID- 27709100
TI  - Surgical advancements in pediatric epilepsy surgery: from the mysterious to the
      minimally invasive.

PMID- 27709101
TI  - Klinefelter syndrome: fertility considerations and gaps in knowledge.

PMID- 27709103
TI  - The Tip of the Iceberg: On the Roles of Regulatory Small RNAs in the Virulence of
      Enterohemorrhagic and Enteropathogenic Escherichia coli.
AB  - Enterohemorrhagic and enteropathogenic Escherichia coli are gastrointestinal
      pathogens that disrupt the intestinal microvilli to form attaching and effacing
      (A/E) lesions on infected cells and cause diarrhea. This pathomorphological trait
      is encoded within the pathogenicity island locus of enterocyte effacement (LEE).
      The LEE houses a type 3 secretion system (T3SS), which upon assembly bridges the
      bacterial cytosol to that of the host and enables the bacterium to traffic dozens
      of effectors into the host where they hijack regulatory and signal transduction
      pathways and contribute to bacterial colonization and disease. Owing to the
      importance of the LEE to EHEC and EPEC pathogenesis, much of the research on
      these pathogens has centered on its regulation. To date, over 40 proteinaceous
      factors have been identified that control the LEE at various hierarchical levels
      of gene expression. In contrast, RNA-based regulatory mechanisms that converge on
      the LEE have only just begun to be unraveled. In this minireview, we highlight
      major breakthroughs in small RNAs (sRNAs)-dependent regulation of the LEE, with
      an emphasis on their mechanisms of action and/or LEE-encoded targets.

PMID- 27709102
TI  - Macrolide Resistance in Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a common commensal and an opportunistic pathogen.
      Suspected pneumococcal upper respiratory infections and pneumonia are often
      treated with macrolide antibiotics. Macrolides are bacteriostatic antibiotics and
      inhibit protein synthesis by binding to the 50S ribosomal subunit. The widespread
      use of macrolides is associated with increased macrolide resistance in S.
      pneumoniae, and the treatment of pneumococcal infections with macrolides may be
      associated with clinical failures. In S. pneumoniae, macrolide resistance is due
      to ribosomal dimethylation by an enzyme encoded by erm(B), efflux by a two
      component efflux pump encoded by mef (E)/mel(msr(D)) and, less commonly,
      mutations of the ribosomal target site of macrolides. A wide array of genetic
      elements have emerged that facilitate macrolide resistance in S. pneumoniae; for
      example erm(B) is found on Tn917, while the mef (E)/mel operon is carried on the
      5.4- or 5.5-kb Mega element. The macrolide resistance determinants, erm(B) and
      mef (E)/mel, are also found on large composite Tn916-like elements most notably
      Tn6002, Tn2009, and Tn2010. Introductions of 7-valent and 13-valent pneumococcal
      conjugate vaccines (PCV-7 and PCV-13) have decreased the incidence of macrolide
      resistant invasive pneumococcal disease, but serotype replacement and emergence
      of macrolide resistance remain an important concern.

PMID- 27709104
TI  - Positive Feedback Cycle of TNFalpha Promotes Staphylococcal Enterotoxin B-Induced
      THP-1 Cell Apoptosis.
AB  - Staphylococcal enterotoxin B (SEB) has been demonstrated to be of importance in
      Staphylococcus aureus related diseases, such as atopic dermatitis (AD).
      Dysregulated apoptosis in AD is remarkable, and SEB can induce apoptosis of
      various cell types. However, the mechanisms by which SEB induces apoptosis and
      influences disease processes remain unclear. In this study, the recombinant SEB
      induced THP-1 monocyte apoptosis was demonstrated in the absence of preliminary
      cell activation in a time- and dose-dependent manner. SEB could up-regulate the
      expression of tumor necrosis factor alpha (TNFalpha) in THP-1 cells and induce
      apoptosis via an extrinsic pathway. TNFalpha could in turn increase the
      expression of HLA-DRa, the SEB receptor on the cell surface. As a result, a
      positive feedback cycle of TNFalpha was established. TNFalpha expression and SEB
      induced apoptosis were decreased by knocking down the expression of either HLA
      DRa or TNFR1. Therefore, the feedback cycle of TNFalpha is crucial for SEB
      functions. This work provides insights into the mechanisms of SEB-induced
      monocyte apoptosis and emphasizes the major role of TNFalpha in future related
      studies.

PMID- 27709106
TI  - Nutritional knowledge, attitude and practice toward micronutrients among Iranian
      households: the NUTRI-KAP survey.
AB  - BACKGROUND: Healthy diet for maintaining a healthy weight and prevention of
      chronic disease is vital at all stages of life. The purpose of this study was to
      determine the nutritional knowledge, attitude, and practice among urban and rural
      households in Iran. METHODS: In this nation-wide study, 14,136 subjects were
      selected using a multistage cluster sampling method from 31 provinces of Iran.
      This study was on the households in rural and urban areas in Iran. Participants
      of this study were mothers or other members who were responsible for preparing
      meals for the whole family. Data were gathered by the questionnaire and the
      interview with the qualified person in each family. RESULTS: Frequency of
      knowledge about food source of calcium was between 11.6 and 64.7 %. Knowing of
      food source of zinc was about 12.8-16.7 %. Knowledge about of meat as source of
      iron was 50.9 and 46.5 % in regions of urban and rural, respectively. Positive
      attitude about preferring to use the full-fat dairy was about 25.1 % and negative
      attitude about this issue was 71.4 %; the positive attitude was slightly lower in
      rural areas than in urban areas. Respectively, frequency of using red meat in
      urban households was 10.8, 73.7, and 15.5 % as daily, weekly and rarely.
      Frequency of using daily of milk, yogurt and cheese was significantly lower in
      rural than in urban household. CONCLUSION: This national study indicates that in
      some cases there is a gap between knowledge and behavior among household of
      Iranian population.

PMID- 27709105
TI  - Differential association of plasma monocyte chemoattractant protein-1 with
      systemic inflammatory and airway remodeling biomarkers in type-2 diabetic
      patients with and without asthma.
AB  - BACKGROUND: Chronic inflammation is a hallmark of type-2 diabetes (T2D) and
      asthma. Monocyte chemoattractant protein (MCP)-1 or CCL-2 is a key regulator of
      monocytic infiltration into the sites of inflammation. The changes in systemic
      MCP-1 levels and its relationship with other inflammatory/immune markers in T2D
      patients with asthma remain unclear and have been addressed in this study.
      METHODS: Plasma samples from 10 asthmatic T2D patients (Group I: BMI = 37.82 +/-
      9.75 kg/m2), 13 non-asthmatic T2D patients (Group II: BMI = 32.68 +/- 4.63
      kg/m2), 23 asthma patients without T2D (Group III: BMI = 30.14 +/- 6.74 kg/m2),
      and 25 non-asthmatic non-diabetic controls (Group IV: BMI = 27.99 +/- 5.86 kg/m2)
      were used to measure levels of MCP-1 and multiple cytokine/chemokine biomarkers
      with bead-based multiplex assays using Luminex technology. IgE/ECP were measured
      using commercial ELISA kits. Data (mean +/- SEM) were compared using unpaired
      Student's t-test and linear dependence between two variables was assessed by
      Pearson's correlation coefficient (r) and P <= 0.05 was considered as
      significant. RESULTS: Plasma MCP-1 levels were significantly higher in Group I
      (337.95 +/- 46.40 pg/mL) as compared with Group II (216.69 +/- 17.30 pg/mL),
      Group III (251.76 +/- 19.80 pg/mL), and Group IV (223.52 +/- 133.36 pg/mL). MCP-1
      showed differential association with tested biomarkers by correlating positively
      with: (i) IFN-alpha2, IL-10, fractalkine, and VEGF in T2D patients with asthma;
      (ii) IL-6 and GRO-alpha in T2D patients without asthma; (iii) MDC, IP-10, GM-CSF,
      FGF-2, and PDGF-AA/BB in patients with asthma only; and (iv) FPG and TG in non
      asthmatic non-diabetic controls. MCP-1 associated with IL-1RA only in subjects
      with asthma. CONCLUSION: The systemic MCP-1 levels were significantly elevated in
      T2D patients with asthma as compared with those without asthma and/or diabetes
      while these changes correlated differentially with important biomarkers of
      inflammation and airway remodeling.

PMID- 27709107
TI  - The Effect of Vascular Neuropathology on Late-life Cognition: Results from the
      SMART Project.
AB  - BACKGROUND: Cerebral vascular pathology may contribute to cognitive decline
      experienced by some elderly near death. Given evidence for mixed neuropathologies
      in advanced age, preventing or reducing cerebrovascular burden in late life may
      be beneficial. OBJECTIVE: To correlate measures of cerebral vascular pathology
      with cognitive trajectories. SETTING: Observational study. PARTICIPANTS: A cohort
      of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82
      percent of whom had at least two cognitive assessments within the last six years
      of life was compiled from six centers conducting longitudinal studies.
      MEASUREMENTS: For each cognitive domain: immediate and delayed memory, language,
      and naming, three trajectories were examined: good, intermediate, and poor
      cognition. The probability of a participant belonging to each trajectory was
      associated with measures of cerebral vascular pathology after adjustment for
      demographics, APOE, and Alzheimer neuropathology. RESULTS: A large proportion of
      the cohort (72-94%) experienced good or intermediate cognition in the four
      domains examined. The presence of arteriolosclerosis and the presence of lacunar
      infarcts doubled the odds of belonging to the poor cognitive trajectory for
      language when compared to the good trajectory. The presence of lacunar infarcts
      increased the odds of an intermediate or poor trajectory for immediate and
      delayed recall while the presence of large artery infarcts increased the odds of
      poor trajectories for all four cognitive domains examined. Microinfarcts and
      cerebral amyloid angiopathy had little effect on the trajectories. CONCLUSION:
      Indicators of cerebral vascular pathology act differently on late life cognition.

PMID- 27709109
TI  - Defining Sudden Infant Death and Sudden Intrauterine Unexpected Death Syndromes
      with Regard to Anatomo-Pathological Examination.
AB  - Crib death, or sudden infant death syndrome (SIDS), is the most frequent form of
      death in the first year of life, striking one baby in every 1,700-2,000. Yet,
      despite advances in maternal-infant care, sudden intrauterine
      unexplained/unexpected death syndrome (SIUDS) has a sixfold to eightfold greater
      incidence than that of SIDS. Frequent congenital abnormalities, likely
      morphological substrates for SIDS-SIUDS, were detected, mainly represented by
      alterations of the cardiac conduction system, such as accessory pathways and
      abnormal resorptive degeneration, and hypoplasia/agenesis of the vital brainstem
      structures. On the basis of these considerations, the new common definition of
      the SIDS-SIUDS complex is "The sudden death of a fetus after the 25th gestational
      week or infant under one year of age which is unexpected by history and remains
      unexplained after a thorough case investigation, including examination of the
      death scene, performance of a general autopsy and examination of the fetal
      adnexa". Therefore, given that the general autopsy does not disclose any cause of
      death, a more in-depth histopathological analysis of the cardiac conduction
      system and autonomic nervous system by specialized pathologists is necessary.

PMID- 27709108
TI  - Familial and Clinical Correlates in Depressed Adolescents with Borderline
      Personality Disorder Traits.
AB  - INTRODUCTION: Chart review is a low-cost, but highly informative, method to
      describe symptoms, treatment, and risk factors associated with borderline
      personality disorder (BPD) and to adapt screening and intervention to clinical
      reality. Previous chart review studies report more aggressiveness/anger and
      psychotic features in youths with BPD. They show that adverse family environment
      and parental psychopathology constitute important factors for BPD pathology.
      OBJECTIVES: To examine clinical characteristics of depressed BPD adolescents (12
      17 years old) outpatients according to gender and to explore variables which are
      associated with BPD traits. METHODS: A retrospective chart review using the child
      and adolescent version of the retrospective diagnostic instrument for borderlines
      was conducted on 30 depressed adolescents with BPD traits and 28 depressed
      patients without BPD traits. Participants who reached the retrospective
      diagnostic instrument for borderlines threshold for BPD were included in the BPD
      traits group. Comparison analyses were performed using Pearson's Chi-square test.
      Associated factors were determined using regression analyses. RESULTS: BPD traits
      participants were characterized by higher family problems (parental
      psychopathology, parent disagreement/argument, and parent-child relational
      problem), more aggressive symptoms, and higher rates of family intervention and
      hospitalization. A number of familial factors (parental history of delinquency,
      substance use, personality disorders, having siblings, or parental
      disagreement/argument in boys) were associated with BPD traits. Attention seeking
      and problematic functioning (does not adapt well to group activities) were also
      associated with BPD traits. DISCUSSION: Our study stresses the need to assess BPD
      traits in adolescent psychiatric evaluation, especially in the presence of
      aggressive behaviors, family problems and attention seeking. Our results also
      highlight the importance of exploring family characteristics intervention in
      adolescents with BPD traits.

PMID- 27709110
TI  - Why We Move: Social Mobility Behaviors of Non-Disabled and Disabled Children
      across Childcare Contexts.
AB  - BACKGROUND: Social mobility is defined as the co-occurrence of self-directed
      locomotion and direct peer interaction. Social mobility is a product of dynamic
      child-environment interactions and thus likely to vary across contexts (e.g.,
      classroom, gymnasium, and playground). PURPOSE: The purpose of this present study
      was to examine differences in children's social mobility: (1) across contexts by
      age and (2) between non-disabled and disabled children. METHOD: Participants (n =
      55 non-disabled and three disabled children; Mage = 3.1 years, SD = 1.4) were
      video recorded within a university-based early learning center. Children were
      recorded for 20 min in each context: classroom, gymnasium, and playground. A 15-s
      momentary time sampling method was used to code social mobility, the simultaneous
      occurrence of self-directed locomotion, and direct peer interaction. This
      variable was calculated as percent time within each context. RESULTS: A planned
      Friedman's rank ANOVA (n = 55), stratified by age, indicated that older children
      (3-5 years old) differed across contexts in their social mobility [chi2(2) ~ 7.3
      10.5, p < 0.025], whereas younger children (1-2 years old) were similar across
      contexts. Social mobility was significantly lower in the classroom compared with
      the playground and gymnasium (with no difference between the latter contexts) for
      older children. Visual analysis confirmed that disabled children (n = 3) engaged
      in substantially less time in social mobility (average 0-1%), compared with non
      disabled, age-similar peers (2-3 years old average 1-12%) across all contexts.
      CONCLUSION: A substantial gap exists between non-disabled and disabled children
      for social mobility. There is an increase in magnitude and variability of social
      mobility around age three that suggests the gap between non-disabled and disabled
      children will continue to widen.

PMID- 27709112
TI  - Autocrine VEGF Isoforms Differentially Regulate Endothelial Cell Behavior.
AB  - Vascular endothelial growth factor A (VEGF) is involved in all the essential
      biology of endothelial cells, from proliferation to vessel function, by mediating
      intercellular interactions and monolayer integrity. It is expressed as three
      major alternative spliced variants. In mice, these are VEGF120, VEGF164, and
      VEGF188, each with different affinities for extracellular matrices and cell
      surfaces, depending on the inclusion of heparin-binding sites, encoded by exons 6
      and 7. To determine the role of each VEGF isoform in endothelial homeostasis, we
      compared phenotypes of primary endothelial cells isolated from lungs of mice
      expressing single VEGF isoforms in normoxic and hypoxic conditions. The
      differential expression and distribution of VEGF isoforms affect endothelial cell
      functions, such as proliferation, adhesion, migration, and integrity, which are
      dependent on the stability of and affinity to VEGF receptor 2 (VEGFR2). We found
      a correlation between autocrine VEGF164 and VEGFR2 stability, which is also
      associated with increased expression of proteins involved in cell adhesion.
      Endothelial cells expressing only VEGF188, which localizes to extracellular
      matrices or cell surfaces, presented a mesenchymal morphology and weakened
      monolayer integrity. Cells expressing only VEGF120 lacked stable VEGFR2 and
      dysfunctional downstream processes, rendering the cells unviable. Endothelial
      cells expressing these different isoforms in isolation also had differing rates
      of apoptosis, proliferation, and signaling via nitric oxide (NO) synthesis. These
      data indicate that autocrine signaling of each VEGF isoform has unique functions
      on endothelial homeostasis and response to hypoxia, due to both distinct VEGF
      distribution and VEGFR2 stability, which appears to be, at least partly, affected
      by differential NO production. This study demonstrates that each autocrine VEGF
      isoform has a distinct effect on downstream functions, namely VEGFR2-regulated
      endothelial cell homeostasis in normoxia and hypoxia.

PMID- 27709111
TI  - Fluidic Logic Used in a Systems Approach to Enable Integrated Single-Cell
      Functional Analysis.
AB  - The study of single cells has evolved over the past several years to include
      expression and genomic analysis of an increasing number of single cells. Several
      studies have demonstrated wide spread variation and heterogeneity within cell
      populations of similar phenotype. While the characterization of these populations
      will likely set the foundation for our understanding of genomic- and expression
      based diversity, it will not be able to link the functional differences of a
      single cell to its underlying genomic structure and activity. Currently, it is
      difficult to perturb single cells in a controlled environment, monitor and
      measure the response due to perturbation, and link these response measurements to
      downstream genomic and transcriptomic analysis. In order to address this
      challenge, we developed a platform to integrate and miniaturize many of the
      experimental steps required to study single-cell function. The heart of this
      platform is an elastomer-based integrated fluidic circuit that uses fluidic logic
      to select and sequester specific single cells based on a phenotypic trait for
      downstream experimentation. Experiments with sequestered cells that have been
      performed include on-chip culture, exposure to various stimulants, and post
      exposure image-based response analysis, followed by preparation of the mRNA
      transcriptome for massively parallel sequencing analysis. The flexible system
      embodies experimental design and execution that enable routine functional studies
      of single cells.

PMID- 27709115
TI  - In Search of the Urban Cowboy: The Need to Incorporate Animal Husbandry into the
      United States Higher Education Curriculum and Its Implications for Production
      Animal Welfare.

PMID- 27709114
TI  - Metal-Induced Stabilization and Activation of Plasmid Replication Initiator RepB.
AB  - Initiation of plasmid rolling circle replication (RCR) is catalyzed by a plasmid
      encoded Rep protein that performs a Tyr- and metal-dependent site-specific
      cleavage of one DNA strand within the double-strand origin (dso) of replication.
      The crystal structure of RepB, the initiator protein of the streptococcal plasmid
      pMV158, constitutes the first example of a Rep protein structure from RCR
      plasmids. It forms a toroidal homohexameric ring where each RepB protomer
      consists of two domains: the C-terminal domain involved in oligomerization and
      the N-terminal domain containing the DNA-binding and endonuclease activities.
      Binding of Mn2+ to the active site is essential for the catalytic activity of
      RepB. In this work, we have studied the effects of metal binding on the structure
      and thermostability of full-length hexameric RepB and each of its separate
      domains by using different biophysical approaches. The analysis of the
      temperature-induced changes in RepB shows that the first thermal transition,
      which occurs at a range of temperatures physiologically relevant for the pMV158
      pneumococcal host, represents an irreversible conformational change that affects
      the secondary and tertiary structure of the protein, which becomes prone to self
      associate. This transition, which is also shown to result in loss of DNA binding
      capacity and catalytic activity of RepB, is confined to its N-terminal domain.
      Mn2+ protects the protein from undergoing this detrimental conformational change
      and the observed protection correlates well with the high-affinity binding of the
      cation to the active site, as substituting one of the metal-ligands at this site
      impairs both the protein affinity for Mn2+and the Mn2+-driven thermostabilization
      effect. The level of catalytic activity of the protein, especially in the case of
      full-length RepB, cannot be explained based only on the high-affinity binding of
      Mn2+ at the active site and suggests the existence of additional, lower-affinity
      metal binding site(s), missing in the separate catalytic domain, that must also
      be saturated for maximal activity. The molecular bases of the thermostabilizing
      effect of Mn2+ on the N-terminal domain of the protein as well as the potential
      location of additional metal binding sites in the entire RepB are discussed.

PMID- 27709113
TI  - Evaluation of Cysteinyl Leukotriene Signaling as a Therapeutic Target for
      Colorectal Cancer.
AB  - Colorectal cancer is the third most common cancer worldwide and is associated
      with significant morbidity and mortality. Current pharmacotherapy options include
      cytotoxic chemotherapy, anti-VEGF, and anti-EGFR targeting drugs, but these are
      limited by toxic side effects, limited responses and ultimately resistance.
      Cysteinyl leukotriene (CysLT) signaling regulates intestinal homeostasis with
      mounting evidence suggesting that CysLT signaling also plays a role in the
      pathogenesis of colorectal cancer. Therefore, CysLT signaling represents a novel
      target for this malignancy. This review evaluates reported links between CysLT
      signaling and established hallmarks of cancer in addition to its pharmacological
      potential as a new therapeutic target.

PMID- 27709116
TI  - Dynamic Simulation of the Effects of Graft Fixation Errors During Medial
      Patellofemoral Ligament Reconstruction.
AB  - BACKGROUND: Medial patellofemoral ligament (MPFL) reconstruction is performed to
      prevent recurrent instability, but errors in femoral fixation can elevate graft
      tension. HYPOTHESIS: Errors related to femoral fixation will overconstrain the
      patella and increase medial patellofemoral pressures. STUDY DESIGN: Controlled
      laboratory study. METHODS: Five knees with patellar instability were represented
      with computational models. Kinematics during knee extension were characterized
      from computational reconstruction of motion performed within a dynamic computed
      tomography (CT) scanner. Multibody dynamic simulation of knee extension, with
      discrete element analysis used to quantify contact pressures, was performed for
      the preoperative condition and after MPFL reconstruction. A standard femoral
      attachment and graft resting length were set for each knee. The resting length
      was decreased by 2 mm, and the femoral attachment was shifted 5 mm posteriorly.
      The simulated errors were also combined. Root-mean-square errors were quantified
      for the comparison of preoperative patellar lateral shift and tilt between
      computationally reconstructed motion and dynamic simulation. Simulation output
      was compared between the preoperative and MPFL reconstruction conditions with
      repeated-measures Friedman tests and Dunnett comparisons against a control, which
      was the standard MPFL condition, with statistical significance set at P < .05.
      RESULTS: Root-mean-square errors for simulated patellar tilt and shift were 5.8
      degrees  and 3.3 mm, respectively. Patellar lateral tracking for the preoperative
      condition was significantly larger near full extension compared with the standard
      MPFL reconstruction (mean differences of 8 mm and 13 degrees  for shift and tilt,
      respectively, at 0 degrees ), and lateral tracking was significantly smaller for
      a posterior femoral attachment (mean differences of 3 mm and 4 degrees  for shift
      and tilt, respectively, at 0 degrees ). The maximum medial pressure was also
      larger for the short graft with a posterior femoral attachment than for standard
      MPFL reconstruction, with a significant increase in the mean value of 1.6 MPa at
      30 degrees . CONCLUSION: MPFL reconstruction reduces lateral tracking, but
      nonanatomic femoral fixation and overtensioning the graft overcorrect patellar
      tracking and increase pressure applied to medial patellar cartilage. CLINICAL
      RELEVANCE: Errors in femoral fixation and graft tensioning can lead to
      postoperative loss of flexion and overloading of medial cartilage.

PMID- 27709118
TI  - Ex vivo Co-culture of Lymphoid Tissue Stromal Cells and T Cells.
AB  - Stromal cells within lymphoid tissues produce IL-7, which is critical for the
      survival and function of T cells. This protocol is to be used to isolate primary
      human lymphoid tissue stromal cells to study their impact on the survival of T
      cells in an ex vivo co-culture system.

PMID- 27709117
TI  - Genetic and Clinical Predictors of Deep Brain Stimulation in Young-Onset
      Parkinson's Disease.
AB  - OBJECTIVE: In a cohort of patients with young-onset Parkinson's disease (PD), the
      authors assessed (1) the prevalence of genetic mutations in those who enrolled in
      deep brain stimulation (DBS) programs compared with those who did not enroll DBS
      programs and (2) specific genetic and clinical predictors of DBS enrollment.
      METHODS: Subjects were participants from 3 sites (Columbia University, Rush
      University, and the University of Pennsylvania) in the Consortium on Risk for
      Early Onset Parkinson's Disease (CORE-PD) who had an age at onset < 51 years. The
      analyses presented here focus on glucocerebrosidase (GBA), leucine-rich repeat
      kinase 2 (LRRK2), and parkin (PRKN) mutation carriers. Mutation carrier status,
      demographic data, and disease characteristics in individuals who did and did not
      enroll in DBS were analyzed. The association between mutation status and DBS
      placement was assessed in logistic regression models. RESULTS: Patients who had
      PD with either GBA, LRRK2, or PRKN mutations were more common in the DBS group (n
      = 99) compared with the non-DBS group (n = 684; 26.5% vs. 16.8%, respectively; P
      = 0.02). In a multivariate logistic regression model, GBA mutation status (odds
      ratio, 2.1; 95% confidence interval, 1.0-4.3; P = 0.05) was associated with DBS
      surgery enrollment. However, when dyskinesia was included in the multivariate
      logistic regression model, dyskinesia had a strong association with DBS placement
      (odds ratio, 3.8; 95% confidence interval, 1.9-7.3; P < 0.0001), whereas the
      association between GBA mutation status and DBS placement did not persist (P =
      0.25). CONCLUSIONS: DBS populations are enriched with genetic mutation carriers.
      The effect of genetic mutation carriers on DBS outcomes warrants further
      exploration.

PMID- 27709119
TI  - Latina/o or Mexicana/o?: The Relationship between Socially Assigned Race and
      Experiences with Discrimination.
AB  - Discrimination based on one's racial or ethnic background is one of the oldest
      and most perverse practices in the United States. While much of this research has
      relied on self-reported racial categories, a growing body of research is
      attempting to measure race through socially-assigned race. Socially-assigned or
      ascribed race measures how individuals feel they are classified by other people.
      This paper draws on the socially assigned race literature and explores the impact
      of socially assigned race on experiences with discrimination using a 2011
      nationally representative sample of Latina/os (n=1,200). While much of the
      current research on Latina/os has been focused on the aggregation across national
      origin group members, this paper marks a deviation by using socially-assigned
      race and national origin to understand how being ascribed as Mexican is
      associated with experiences of discrimination. We find evidence that being
      ascribed as Mexican increases the likelihood of experiencing discrimination
      relative to being ascribed as White or Latina/o. Furthermore, we find that being
      miss-classified as Mexican (ascribed as Mexican, but not of Mexican origin) is
      associated with a higher likelihood of experiencing discrimination compared to
      being ascribed as white, ascribed as Latina/o, and correctly ascribed as Mexican.
      We provide evidence that socially assigned race is a valuable complement to self
      identified race/ethnicity for scholars interested in assessing the impact of
      race/ethnicity on a wide range of outcomes.

PMID- 27709121
TI  - Wind tunnel and numerical data on the ventilation performance of windcatcher with
      wing wall.
AB  - The data presented in this article were the basis for the study reported in the
      research articles entitled "Evaluation of a two-sided windcatcher integrated with
      wing wall (as a new design) and comparison with a conventional windcatcher" (P.
      Nejat, J.K. Calautit, M.Z.A. Majid, B.R. Hughes, I. Zeynali, F. Jomehzadeh, 2016)
      [1] which presents the effect of wing wall on the air flow distribution under
      using the windcatchers as a natural ventilation equipment. Here, we detail the
      wind tunnel testing and numerical set-up used for obtaining the data on
      ventilation rates and indoor airflow distribution inside a test room with a two
      sided windcatcher and wing wall. Three models were integrated with wing wall
      angled at 30 degrees , 45 degrees  and 60 degrees  and another windcatcher was a
      conventional two-sided device. The computer-aided design (CAD) three-dimensional
      geometries which were produced using Solid Edge modeler are also included in the
      data article.

PMID- 27709120
TI  - MRI features in 17 patients with l2 hydroxyglutaric aciduria.
AB  - l-2-Hydroxyglutaric (l-2-HG) aciduria is a rare inherited metabolic disease
      usually observed in children. Patients present a very slowly progressive
      deterioration with cerebellar ataxia, mild or severe mental retardation, and
      various other clinical signs including extrapyramidal and pyramidal symptoms, and
      seizures Goffette et al. [1]. This leukencephalopathy was first described in 1980
      Duran et al. [2]. Brain magnetic resonance imaging (MRI) demonstrates nonspecific
      subcortical white matter (WM) loss, cerebellar atrophy and changes in dentate
      nuclei and putamen Steenweg et al. [3]. The diagnosis is highlighted by increased
      levels of l-2-HG in body fluids such as urine and cerebrospinal fluid. The
      purpose of this study is to retrospectively describe the brain MRI features in l
      2-HG aciduria.

PMID- 27709122
TI  - Dataset of near infrared spectroscopy measurements to predict rheological
      parameters of sludge.
AB  - In the dataset presented in this article, 36 sludge samples were characterized.
      Rheological parameters were determined and near infrared spectroscopy
      measurements were realized. In order to assess the potential of near infrared
      spectroscopy to predict rheological parameters of sludge, Partial Least Square
      algorithm was used to build calibration models.

PMID- 27709123
TI  - The role of interleukin-1beta in pyoderma gangrenosum.

PMID- 27709124
TI  - Rosai-Dorfman disease successfully treated with thalidomide.

PMID- 27709127
TI  - Human induced pluripotent stem cell-derived cardiac tissue on a thin collagen
      membrane with natural microstructures.
AB  - Human induced pluripotent stem cells (hiPSCs) and appropriate scaffolds are of
      great interest in cardiac tissue engineering. In this work, we present a simple
      and new strategy to produce a thin collagen membrane with a natural
      microstructure from porcine tendons and reconstruct the functional cardiac
      tissues by recellularizing hiPSC-derived cardiomyocytes onto the membrane, for
      the first time. The collagen membrane maintained its intact properties after
      decellularization, the composition of which was identified as collagen I. The
      cardiomyocytes grown on the thin membrane strongly expressed the cardiac-specific
      marker cardiac troponin T and exhibited the specific morphology guided by the
      natural microstructure of the collagen fibers. The formed cardiac tissue could
      maintain a strong beating function spontaneously for over one month and respond
      rapidly to the two types of anti-arrhythmic drugs with opposed effects. The
      proposed approach is very simple, and easy to operate with a low cost. The
      obtained thin collagen membrane with a natural microstructure is analogous to the
      in vivo extracellular matrix structure and functions, supporting the good
      function of the engineered cardiac tissue. We envision that this work would open
      a new way for a wide range of applications in cardiac tissue engineering, drug
      testing and regenerative medicine.

PMID- 27709128
TI  - Fast and robust fabrication of reusable molds for hydrogel micro-patterning.
AB  - Mechanical interactions between cells and their microenvironment are crucial for
      fundamental biological processes ranging from migration to differentiation. This
      has led, over the last decades, to the development of new ways to culture cells.
      Living cells are now grown not only on glass coverslips, where they completely
      lose the mechanical and geometrical constraints coming from their
      microenvironment, but also on soft patterned substrates that mimic the rigidity
      and spatial information of their in vivo niches. Microfabrication processes have
      thus logically emerged has new tools to create model environments to probe the
      behavior of biological objects. Here, we present a method for fast and robust
      protein micropattern transfer onto polyacrylamide hydrogels that can be used for
      traction force microscopy. The technique relies on the elaboration of glass
      templates bearing patterned polymer brushes, which can be re-employed several
      times for the production of patterned gels without the need to repeat the
      critical microfabrication steps.

PMID- 27709126
TI  - Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for
      Chagas Disease.
AB  - BACKGROUND: Previously we reported that a hexon-modified adenovirus (Ad) vector
      containing the invasive neutralizing epitope of Trypanosoma cruzi (T. cruzi)
      trypomastigote gp83 (Ad5-gp83) provided immunoprotection against T. cruzi
      infection. The purpose of this work was to design an improved vaccine for T.
      cruzi using a novel epitope capsid incorporation strategy. Thus, we evaluated the
      immunoprotection raised by co-immunization with Ad5-gp83 and an Ad vector
      containing an epitope (ASP-M) of the T. cruzi amastigote surface protein 2.
      METHODS: Protein IX (pIX)-modified Ad vector (Ad5-pIX-ASP-M) was generated,
      characterized, and validated. C3H/He mice were immunized with Ad5-pIX-ASP-M and
      Ad5-gp83 and the cell-mediated responses were evaluated by enzyme-linked
      immunospot (ELISPOT) assay and intracellular staining. Immunized mice were
      challenged with T. cruzi to evaluate the vaccine efficacy. RESULTS: Our findings
      indicate that Ad5-pIX-ASP-M was viable. Specific CD8+ T-cell mediated responses
      prior to the challenge show an increase in IFNgamma and TNFalpha production. A
      single immunization with Ad5-pIX-ASP-M provided protection from T. cruzi
      infection, but co-immunizations with Ad5-pIX-ASP-M and Ad5-gp83 provided a higher
      immunoprotection and increased survival rate of mice. CONCLUSIONS: Overall, these
      results suggest that the combination of gp83 and ASP-M specific epitopes onto the
      capsid-incorporated adenoviruses would provide superior protection against Chagas
      disease as compared with Ad5-gp83 alone.

PMID- 27709125
TI  - Genetic and transcriptional analysis of human host response to healthy gut
      microbiota.
AB  - Many studies have demonstrated the importance of the gut microbiota in healthy
      and disease states. However, establishing the causality of host-microbiota
      interactions in humans is still challenging. Here, we describe a novel
      experimental system to define the transcriptional response induced by the
      microbiota in human cells and to shed light on the molecular mechanisms
      underlying host-gut microbiota interactions. In primary human colonic epithelial
      cells, we identified over 6,000 genes that change expression at various time
      points following co-culturing with the gut microbiota of a healthy individual.
      Among the differentially expressed genes we found a 1.8-fold enrichment of genes
      associated with diseases that have been previously linked to the microbiome, such
      as obesity and colorectal cancer. In addition, our experimental system allowed us
      to identify 87 host SNPs that show allele-specific expression in 69 genes.
      Furthermore, for 12 SNPs in 12 different genes, allele-specific expression is
      conditional on the exposure to the microbiota. Of these 12 genes, eight have been
      associated with diseases linked to the gut microbiota, specifically colorectal
      cancer, obesity and type 2 diabetes. Our study demonstrates a scalable approach
      to study host-gut microbiota interactions and can be used to identify putative
      mechanisms for the interplay between host genetics and microbiota in health and
      disease.

PMID- 27709130
TI  - Synthesis and characterization of biodegradable lysine-based waterborne
      polyurethane for soft tissue engineering applications.
AB  - Biomaterials for soft tissue engineering scaffolds require a combination of
      multiple properties including suitable mechanical properties, biodegradability,
      and biocompatibility. In this work, a series of light-crosslinking waterborne
      polyurethanes (LWPUs) were prepared using l-lysine ethyl ester diisocyanate
      (LDI), 1,3-propanediol (PDO) and l-lysine as hard segments and poly(epsilon
      caprolactone) (PCL) and poly(ethylene glycol) (PEG) as soft segments. The
      obtained LWPUs exhibited appropriate stretchability with a break elongation of
      1400-2500% and an excellent strength of 12-18 MPa, which could admirably meet the
      requirements for soft tissue engineering scaffolds. In addition, the hydrophilic
      surfaces of LWPUs could effectively reduce protein adsorption and platelet
      adhesion and favor cell proliferation compared with traditional biomedical
      polyurethanes. The ultimate degradation products of LWPUs were proven to be
      nontoxic in a cytotoxicity test. More interestingly, a cytokine release test of
      macrophages adherent to the LWPU film surfaces shows that these macrophages
      secreted less pro-inflammation cytokine TNF-alpha and more anti-inflammation
      cytokine IL-10 after 3 days' culture, indicating that LWPUs possess the potential
      ability to aid in the transition of macrophages toward a wound healing phenotype.
      Furthermore, the LWPU films could support the adhesion and proliferation of
      endothelial cells. Thus, the obtained LWPUs have great potential for applications
      in soft tissue engineering scaffolds for tissue repair and wound healing.

PMID- 27709129
TI  - Cellular uptake of drug loaded spider silk particles.
AB  - Medical therapies are often accompanied by un-wanted side-effects or, even worse,
      targeted cells can develop drug resistance leading to an ineffective treatment.
      Therefore, drug delivery systems are under investigation to lower the risk
      thereof. Drug carriers should be biocompatible, biodegradable, nontoxic, non
      immunogenic, and should show controllable drug loading and release properties.
      Previous studies qualified spider silk particles as drug delivery carriers,
      however, cellular uptake was only tested with unloaded spider silk particles.
      Here, the effect of drug loading on cellular uptake of previously established
      spider silk-based particles made of eADF4(C16), eADF4(C16)RGD, eADF4(C16)R8G and
      eADF4(kappa16) was investigated. Fluorescently labelled polyethylenimine was used
      as a model substance for loading eADF4(C16), eADF4(C16)RGD or eADF4(C16)R8G
      particles, and fluorescently labelled ssDNA was used for loading eADF4(kappa16)
      particles. Upon loading polyanionic eADF4(C16) and eADF4(C16)RGD particles with
      polycationic polyethylenimine the cellular uptake efficiency was increased, while
      the uptake of eADF4(C16)R8G and polycationic eADF4(kappa16) particles was
      decreased upon substance loading. The latter could be circumvented by coating
      substance-loaded eADF4(kappa16) particles with an additional layer of
      eADF4(kappa16) (layer-by-layer coating). Further, it could be shown that
      eADF4(C16)RGD and eADF4(kappa16) uptake was based on clathrin-mediated
      endocytosis, whereas macropinocytosis was more important in case of eADF4(C16)
      and eADF4(C16)R8G particle uptake. Finally, it was confirmed that drugs, such as
      doxorubicin, can be efficiently delivered into and released within cells when
      spider silk particles were used as a carrier.

PMID- 27709131
TI  - Near infrared imaging-guided photodynamic therapy under an extremely low energy
      of light by galactose targeted amphiphilic polypeptide micelle encapsulating
      BODIPY-Br2.
AB  - Near infrared (NIR) imaging-guided photodynamic therapy (PDT) is attractive,
      especially the utilization of one dye as both a photosensitizer and fluorescent
      probe, and the as-synthesized BODIPY-Br2 molecule is a candidate. Here, a
      galactose targeted amphiphilic copolymer of a polypeptide was synthesized and its
      micelles work as nanocarriers for BODIPY for targeting the NIR imaging-guided PDT
      of hepatoma cancer cells. At the same time, BODIPY could light up the cytoplasm
      for real-time imaging and kill cancer cells when the light was switched on. In
      vitro tests performed on both HepG2 and HeLa cells confirmed that the as-prepared
      PMAGP-POEGMA-PLys-B micelles showed efficient cell suppression of the cells with
      galactose receptors in the presence of light under an extremely low energy
      density (6.5 J cm-2). This protocol highlights the potential of polypeptides as
      biodegradable carriers for NIR image-guided and confined targeting photodynamic
      therapy.

PMID- 27709132
TI  - Improved osteogenesis and angiogenesis of magnesium-doped calcium phosphate
      cement via macrophage immunomodulation.
AB  - Immune responses are vital for bone regeneration and play an essential role in
      the fate of biomaterials after implantation. As a kind of plastic cell,
      macrophages are central regulators of the immune response during the infection
      and wound healing process including osteogenesis and angiogenesis. Magnesium
      calcium phosphate cement (MCPC) has been reported as a promising candidate for
      bone repair with promoted osteogenesis both in vitro and in vivo. However,
      relatively little is known about the effects of MCPC on immune response and the
      following outcome. In this study, we investigated the interactions between
      macrophages and MCPC. Here we found that the pro-inflammatory cytokines including
      TNF-alpha and IL-6 were less expressed and the bone repair related cytokine of
      TGF-beta1 was up-regulated by macrophages in MCPC extract. Furthermore, the
      enhanced osteogenic capacity of BMSCs and angiogenic potential of HUVECs were
      acquired in vitro by the MCPC-induced immune microenvironment. These findings
      suggest that MCPC is able to facilitate bone healing by endowing favorable
      osteoimmunomodulatory properties and influencing crosstalk behavior between
      immune cells and osteogenesis-related cells.

PMID- 27709133
TI  - Rheological properties, biocompatibility and in vivo performance of new hydrogel
      based bone fillers.
AB  - Three different heterologous substitutes for bone regeneration, manufactured with
      equine-derived cortical powder (CP), cancellous chips (CC) and demineralized bone
      matrix granules (DBM), were compared in in vitro and in vivo settings. We tested:
      a commercially available bone paste (Osteoplant-ActivagenTM, consisting of
      aqueous collagenous carrier, CP, DBM; named A); a second-generation injectable
      paste (20 kDa polyethylene glycol/hydroxypropyl-methyl cellulose-based hydrogel,
      CP, DBM; B); a pre-formed bone filler (400 kDa polyethylene oxide/hydroxypropyl
      methyl cellulose-based hydrogel, CP, CC, DBM; C). Vitamin C acted as a visco
      modulator during C and B beta-rays sterilization, modifying graft injectability.
      For each filler, we examined dissolution in culture medium, gene expression of
      the substitute-exposed osteogenically-induced human bone marrow stromal cells
      (hBMSC), and performance in a rabbit bone defect model. A dissolved after 1 h,
      while fragmentation of B peaked after 8 h. C remained unaltered for 2 days, but
      affected the microenvironmental pH, slowing the proliferation of exposed cells. B
      exposed hBMSC overexpressed bone sialoprotein, osteocalcin and RUNX2. For all
      fillers histological results evidenced bridged lesion margins, marrow
      replenishment and bone-remodeling. However, B-treated lesions displayed a
      metachromatic type II collagen-rich matrix with prehypertrophic-like cells,
      matching the in vitro expression of cartilage-specific markers, and suggesting a
      possible application of B/C double-layer monolithic osteochondral plugs for full
      thickness articular defects.

PMID- 27709134
TI  - Polycaprolactone-chitosan nanofibers influence cell morphology to induce early
      osteogenic differentiation.
AB  - Osteogenic differentiation is highly correlated with cell morphology.
      Morphological changes are a stimulus as well as a consequence of the
      differentiation process. Besides, geometrical, biochemical and mechanical
      properties of a substrate can modulate cell adhesion and morphology. Therefore,
      in the current study, nanofibrous substrate properties were used to implement
      necessary changes in cell morphology which induced osteogenic differentiation
      without biological supplements. A polycaprolactone-chitosan nanofiber substrate
      had been fabricated with an average diameter of ~75 nm and an appropriate ratio
      of polymers that balances surface biocompatibility as well as mechanical
      strength. DSC and wide-angle XRD analysis revealed miscibility between polymers;
      whereas a degradation study confirmed the structural integrity of nanofibers.
      Nanofibers did not cause any cytotoxicity to MC3T3-E1 cells as confirmed by
      Live/Dead(r) staining. Morphological studies by SEM and confocal microscopy
      showed significant changes in terms of cell shape, area, compactness, aspect
      ratio and nucleus area in cells grown on nanofibers which indicated the
      osteogenic differentiation inducing potential of nanofibers. This was further
      confirmed by enhanced mineral deposition and alkaline phosphatase activity up to
      three weeks. In summary, polycaprolactone-chitosan nanofibers could induce early
      osteogenic differentiation in MC3T3-E1 pre-osteoblasts without any biological
      supplements by modulating cell morphology. Moreover, cell morphological features
      can be used as a predictive and informative approach at the early stages of
      differentiation experiments.

PMID- 27709135
TI  - Correcting the fundamental ion mobility equation for field effects.
AB  - The fundamental ion mobility equation computes the energy-averaged collision
      cross section as a function of measured drift velocity, electric field strength,
      ion and neutral masses, and drift gas state parameters. As field strength
      approaches zero, in particular when the drift velocity drops below about 4% of
      the average ion-neutral thermal speed, the fundamental equation takes on an
      especially simple form because the collision frequency and average momentum
      transfer become indistinguishable from their thermal values. However, in modern
      high-performance IMS-MS instruments, ion drift velocities may be 10-50% or more
      of thermal speed, and analysis using the zero-field equation gives rise to
      erroneously large cross sections. We address this problem by developing
      correction factors for the zero-field equation from an improved momentum-transfer
      (MT) theory for ion mobility, corrected and completed herein, and from the well
      known two-temperature (2T) theory. The corrected and uncorrected equations are
      compared by their ability to recover known hard-sphere cross sections from
      accurately-computed mobility data. Both MT and 2T expressions adjust for the
      field-driven increase in collision frequency and are noticeably superior to zero
      field expression whenever the ion drift velocity is greater than ~4% of thermal
      speed. The MT expression also adjusts for the mass and field dependent change in
      average momentum transfer, and is more accurate than the 2T first approximation
      whenever the mass of the ionic species is greater than about four times that of
      drift gas molecules, as is the case in most analytical applications of IMS
      coupled to MS.

PMID- 27709136
TI  - A thermoresponsive supramolecular copolymer hydrogel for the embolization of
      kidney arteries.
AB  - Our team has previously reported a high strength thermoplastic supramolecular
      polymer hydrogel. However, the hydrogel required injection temperatures outside
      the physiological range therefore preventing its use in a living environment. In
      this article, we reported a thermoresponsive supramolecular copolymer hydrogel
      p(N-acryloyl glycinamide-co-acrylamide) (PNAGA-PAAm), which can be injected at
      temperatures within the physiological range. We used rheological measurements to
      demonstrate that the transition temperature (upper critical solution temperature)
      of both the moduli and gel-sol could be finely adjusted by controlling both the
      ratio and concentration of the monomer. Adding iohexol (contrast agent) in PNAGA
      PAAm hydrogels contributed to the decreased moduli and gel-sol transition
      temperature due to weakening of the hydrogen bonding interactions. The
      cytocompatible and hemocompatible PNAGA-PAAm sol mixed with iohexol was injected
      into the renal arteries of rabbits through a microcatheter at a temperature
      within the high biological range. The transition from the injection temperature
      (high biological range) to body temperature (basal for the animals) quickly
      solidified the embolic agent without the occurrence of dehydration, therefore
      overcoming the main limitation of LCST-typed poly(N-isopropylacrylamide)
      previously reported. Angiography and histological examination demonstrated the
      successful embolization of both renal arteries and no recanalization was observed
      after 8 weeks. The PNAGA-based supramolecular copolymer hydrogel is a novel
      embolic agent that allows for the occlusion of larger sized arteries in a
      biocompatible environment.

PMID- 27709139
TI  - The suppression of metastatic lung cancer by pulmonary administration of polymer
      nanoparticles for co-delivery of doxorubicin and Survivin siRNA.
AB  - A pH-sensitive co-delivery system was designed for the treatment of metastatic
      lung cancers by pulmonary delivery of doxorubicin (DOX) and Survivin siRNA.
      Conjugates PEI-BMPH-DOX (PMD) of polyethylenimine (PEI) with DOX were developed
      via a pH-sensitive hydrazine bond (3-maleimidopropionic acid hydrazide, BMPH).
      Furthermore, the PMD/Survivin siRNA complex nanoparticles were prepared by
      electrostatic interaction between cationic PMD and anionic Survivin siRNA. The
      drug release of DOX from PMD conjugates increased with decreasing pH values. The
      DOX and Survivin siRNA could be effectively delivered into the same cells and
      enhanced the cytotoxicity in B16F10 cells. In the B16F10 tumor-bearing mice
      models, local delivery of PMD/siRNA complex nanoparticles by pulmonary delivery
      resulted in the preferential accumulation of DOX and siRNA in the lungs, and a
      considerable amount of DOX and siRNA accumulated in tumor tissues of the lungs,
      but limited DOX and siRNA were observed in normal lung tissues. Moreover, the
      PMD/Survivin siRNA complex nanoparticles showed enhanced antitumor efficacy
      compared with the mono-delivery of DOX or Survivin siRNA. Taken together, our
      findings offer an effective local delivery strategy by pulmonary administration
      for the treatment of metastatic lung cancer.

PMID- 27709138
TI  - PEG-based hydrogels prepared by catalyst-free thiol-yne addition and their post
      antibacterial modification.
AB  - PEG-based hydrogels possess tissue-like mechanical elasticity, solute
      permeability, cytocompatibility and biocompatibility. In this work, PEG-based
      hydrogels were prepared via nucleophilic thiol-yne addition between a 4-arm PEG
      functionalized with thiols (PEG10k-4-SH) and an electron-deficient alkyne (PEG10k
      4-PP). The as-fabricated hydrogels still possess residual functionalities,
      enabling a second nucleophilic thiol-yne addition on the gel matrix. A thiol
      containing fluorescent dye was conjugated with the electron-deficient alkyne
      appended hydrogels. A thiol-containing antimicrobial peptide (AMP-SH) was also
      embedded into the gel matrix via nucleophilic thiol-yne addition. The inhibition
      of bacterial growth in suspensions and contaminated substrate surfaces by the AMP
      embedded hydrogels was studied. The cytotoxicity of unmodified and AMP-embedded
      PEG-based hydrogels against 3T3 fibroblasts was investigated by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) viability assay.

PMID- 27709145
TI  - Correction: Bottom-up fabrication of artery-mimicking tubular co-cultures in
      collagen-based microchannel scaffolds.
AB  - Correction for 'Bottom-up fabrication of artery-mimicking tubular co-cultures in
      collagen-based microchannel scaffolds' by A. Tan, et al., Biomater. Sci., 2016,
      DOI: 10.1039/c6bm00340k.

PMID- 27709146
TI  - Convex and concave micro-structured silicone controls the shape, but not the
      polarization state of human macrophages.
AB  - The typical foreign body response (FBR) to synthetic implants is characterized by
      local inflammation and tissue fibrosis. Silicone implants have been associated
      with the development of adverse capsular contraction (ACC); a form of excessive
      FBR to the material that often requires the replacement of the implant. It has
      been shown that surface roughening of silicone can reduce the prevalence of ACC,
      but the mechanisms remain poorly understood. Macrophages are key cells in FBR.
      They exert their control mainly by polarizing into pro-inflammatory (M1) or pro
      healing (M2) cells. It is postulated that surface topography can reduce M1
      polarization by limiting cell spreading and cytoskeleton organization. To test
      this hypothesis, we used KrF Excimer laser ablation with half-tone masks to
      produce convex and concave topographies with controlled surface dimensional
      parameters. Cells in convex and concave topographies were compared to cells in
      planar surfaces, with or without chemical polarization. We show that chemical
      polarization induced specific changes in the cell shape on planar substrates.
      Macrophage shape and size was different in concave and convex surfaces, but no
      correlation was found with the cell polarization state. The results highlight
      that chemical polarization of macrophages is associated with changes in the cell
      shape; however, topography-induced changes in macrophage shape could not be
      linked with a shift in macrophage polarization. Thus, the sole manipulation of
      cell shape does not seem to be the mechanism by which macrophage function could
      be controlled.

PMID- 27709137
TI  - Recent trends on hydrogel based drug delivery systems for infectious diseases.
AB  - Since centuries, the rapid spread and cure of infectious diseases have been a
      major concern to the progress and survival of humans. These diseases are a global
      burden and the prominent cause for worldwide deaths and disabilities.
      Nanomedicine has emerged as the most excellent tool to eradicate and halt their
      spread. Various nanoformulations (NFs) using advanced nanotechnology are in
      demand. Recently, hydrogel and nanogel based drug delivery devices have posed new
      prospects to simulate the natural intelligence of various biological systems.
      Owing to their unique porous interpenetrating network design, hydrophobic drug
      incorporation and stimulus sensitivity hydrogels owe excellent potential as
      targeted drug delivery systems. The present review is an attempt to highlight the
      recent trends of hydrogel based drug delivery systems for the delivery of
      therapeutic agents and diagnostics for major infectious diseases including
      acquired immune deficiency syndrome (AIDS), malaria, tuberculosis, influenza and
      ebola. Future prospects and challenges are also described.

PMID- 27709148
TI  - Inorganic-organic hybrid white light phosphors.
AB  - Light-emitting diodes (LEDs) and organic light-emitting diodes (OLEDs) have
      brought about a revolution in lighting and display. A very hot field in recent
      years has been to develop white-light phosphors, aiming to achieve better colour
      stability, better reproducibility, and a simpler fabrication process for LEDs and
      OLEDs. This feature article reviews the development of inorganic-organic hybrid
      white-light phosphors, including coordination compounds of small organic
      molecules, organically templated inorganic compounds (phosphates, borates,
      sulfides, halides), metal-functionalized organic polymers, and organically coated
      nanoparticles.

PMID- 27709147
TI  - Opportunities for glyconanomaterials in personalized medicine.
AB  - In this feature article we discuss the particular relevance of glycans as
      components or targets of functionalized nanoparticles (NPs) for potential
      applications in personalized medicine but we will not enter into descriptions for
      their preparation. For a more general view covering the preparation and
      applications of glyconanomaterials the reader is referred to a number of recent
      reviews. The combination of glyco- and nanotechnology is already providing
      promising new tools for more personalized solutions to diagnostics and therapy.
      Current applications relevant to personalized medicine include drug targeting,
      localized radiation therapy, imaging of glycan expression of cancer cells, point
      of care diagnostics, cancer vaccines, photodynamic therapy, biosensors, and
      glycoproteomics.

PMID- 27709149
TI  - Electron-phonon coupling in engineered magnetic molecules.
AB  - We probe the electron-phonon coupling for in situ engineered porphyrin-based
      magnetic molecular layers supported on weakly reactive surfaces. Using high
      resolution scanning tunneling microscopy and spectroscopy at 4.5 K we show that
      the electronic and magnetic properties of the engineered molecules are the result
      of interplay between many-body spin-flip excitations and electron-phonon
      interactions.

PMID- 27709150
TI  - Ultra-small Ge1-xSnx quantum dots with visible photoluminescence.
AB  - Ge1-xSnx alloy quantum dots (QDs) were synthesized with sizes ranging from 1-3 nm
      exhibiting visible orange-red photoluminescence. Composition dependent optical
      properties were characterized and supported by theoretical calculations.
      Structural analysis suggests the QDs are diamond cubic phase, characteristic of
      Ge1-xSnx thin films and nanocrystals (NCs) reported to date.

PMID- 27709151
TI  - Gold-catalyzed [3+2]-annulations of alpha-aryl diazonitriles with ynamides and
      allenamides to yield 1-amino-1H-indenes.
AB  - Gold-catalyzed [3+2]-annulations of alpha-aryl diazonitriles with ynamides and
      allenamides yield 1-amino-1H-indenes in two distinct pathways; the success of
      these annulations relies on the high electrophilicity of alpha-cyano arylgold
      carbenes to activate an ionic pathway.

PMID- 27709152
TI  - AIE-active tetraphenylethene functionalized metal-organic framework for selective
      detection of nitroaromatic explosives and organic photocatalysis.
AB  - AIE-active luminogen tetraphenylethene (TPE) was incorporated into a UiO
      isoreticular zirconium metal-organic framework via the strategy of mixed
      dicarboxylate struts, and the resulting functionalized MOF shows a strong blue
      green emission and selective sensing of nitroaromatic explosives 2,4,6
      trinitrophenol (TNP) and 2,4-dinitrophenol (DNP) through fluorescence quenching.
      Moreover, the luminescent MOF exhibits efficient photocatalytic activity for
      aerobic cross-dehydrogenative coupling reactions mediated by visible light.

PMID- 27709153
TI  - Rhodium/bisphosphine-thiourea-catalyzed enantioselective hydrogenation of
      alpha,beta-unsaturated N-acylpyrazoles.
AB  - We successfully extended our Rh/bisphosphine-thiourea (ZhaoPhos) catalytic system
      to asymmetric hydrogenation of alpha,beta-unsaturated N-acylpyrazoles affording
      products with high yields and excellent enantioselectivities (up to 97% yield,
      99% ee). The pyrazole moiety played an important role in providing H-bond
      acceptor sites, which is critical for achieving high reactivities and
      enantioselectivities.

PMID- 27709154
TI  - A fast response and red emission probe for mammalian thioredoxin reductase.
AB  - The first red emission off-on probe, TRFS-red, for thioredoxin reductase was
      reported. Compared to the previous green emission probe TRFS-green, TRFS-red
      maintains a high selectivity to the redox enzyme yet with improved response rate
      and sensitivity.

PMID- 27709155
TI  - Beyond energies: geometry predictions with the XYG3 type of doubly hybrid density
      functionals.
AB  - The exchange-correlation functional holds the key to the success or failure of
      density functional theory calculations. When evaluating the functional
      performances, the current literature has focused much more on the ability of the
      method to reproduce exact electronic energies than on exact geometries. As all
      calculations have to start from the right geometries, the present feature article
      explores the functional performances on geometry predictions involving covalently
      and non-covalently bonded systems, as well as transition state structures with
      emphasis on the XYG3 type of doubly hybrid (xDH) functionals. The results are
      also presented for some challenging cases, demonstrating the usefulness of the
      xDH functionals in general.

PMID- 27709156
TI  - Anti-Markovnikov rearrangement in sulfur mediated allylic C-H amination of
      olefins.
AB  - Cationic rearrangement reactions usually follow Markovnikov's rule to give more
      substituted carbocations as stable intermediates. During our study on sulfur
      mediated allylic C-H amination of olefins, very rare cases of anti-Markovnikov
      rearrangement from secondary carbocations toward primary carbocations or primary
      triflates were observed.

PMID- 27709158
TI  - Iodine-promoted cyclization of N-propynyl amides and N-allyl amides via
      sulfonylation and sulfenylation.
AB  - An iodine-promoted regioselective cyclization of N-propynyl/allyl amides with
      sulfonyl hydrazides has been developed for the synthesis of 5-methyl
      arylsulfonyloxazoles and 5-methyl-arylthiooxazolines via sulfonylation and
      sulfenylation reactions. The notable features of this reaction are the formation
      of new C-S and C-O bonds, the broad functional group tolerance, and its
      applicability to alkyl sulfonyl hydrazides as well as internal alkynes.

PMID- 27709157
TI  - Discovery of a VHL and HIF1alpha interaction inhibitor with in vivo angiogenic
      activity via structure-based virtual screening.
AB  - We describe herein compound 1, which is similar to many known natural products,
      as an inhibitor of the VHL-HIF1alpha interaction via structure-based virtual
      screening. Compound 1 disrupts VHL-mediated HIF1alpha degradation, leading to
      significantly increased VEGF expression. To our knowledge, compound 1 is a member
      of only the second class of small molecule inhibitors of the VHL-HIF1alpha
      interaction.

PMID- 27709159
TI  - Enhancement of oxygen evolution performance through synergetic action between
      NiFe metal core and NiFeOx shell.
AB  - NiFe/NiFeOx core/shell electrocatalysts show excellent OER activity by taking
      advantage of the synergetic effect between the metal core and the oxide/hydroxide
      shell, i.e. the metal core provides good bulk electron conduction and thus
      extends the OER active sites to the whole oxide/hydroxide shell, and the shell
      catalyzes the OER and protects the metal core from oxidation.

PMID- 27709160
TI  - A fingerprint of metal-oxide powders: energy-resolved distribution of electron
      traps.
AB  - Here we propose a method for the identification of metal-oxide powders with the
      energy-resolved distribution of electron traps and conduction-band bottom
      position reflecting a surface structure and a bulk structure, respectively, as a
      fingerprint, based on the degree of coincidence for a given pair of samples,
      measured using newly developed reversed double-beam photoacoustic spectroscopy.

PMID- 27709161
TI  - Enantioselective oxidative functionalization of the Csp3-H bond adjacent to a
      nitrogen atom for rapid access to beta-hydroxyl-alpha-amino acid derivatives.
AB  - Highly chemoselective and enantioselective one-pot reactions involved in the
      oxidative functionalization of Csp3-H bonds adjacent to nitrogen atoms in N-aryl
      glycine esters were developed. The method provided rapid access to a variety of
      highly functionalized beta-hydroxyl-alpha-amino acid derivatives from simple
      starting materials under mild conditions.

PMID- 27709162
TI  - Tuning optical properties of perovskite nanocrystals by supermolecular mercapto
      beta-cyclodextrin.
AB  - This study reports a host-guest interaction strategy for systematically
      manipulating the optical properties of cesium lead halide perovskite nanocrystals
      (CsPbBr3 NCs) by protectant-mediated mercapto-beta-cyclodextrin (SH-beta-CD). The
      fluorescence of CsPbBr3 NCs can be adjusted over 405-510 nm with the quantum
      yields (QY) maintained at 50-90%.

PMID- 27709163
TI  - A conformation and charge co-modulated ultrasensitive biomimetic ion channel.
AB  - For the first time, a biomimetic ion channel co-modulated simultaneously by
      conformation and charge using a single stimulus has been demonstrated, and, based
      on the synergetic effect of this channel, an ultrasensitive nanopore sensor for
      ATP with a limit of detection down to sub-pM was developed.

PMID- 27709164
TI  - A metal-organic framework with rod secondary building unit based on the Boerdijk
      Coxeter helix.
AB  - The renowned aperiodic Boerdijk-Coxeter helix is identified, with a modified,
      periodic form, in a MOF named ROD-1 [formulated as Cd(L), H2L = (3,5-dimethyl-1H
      (pyrazol-4-yl)-methylene)benzoic acid], which exhibits unusual gas adsorption
      behaviours attributed to guest-guest interactions, and also interesting
      structural dynamics responding to temperature variation and gas adsorption.

PMID- 27709165
TI  - Cu- and Pd-catalyzed Ullmann reaction on a hexagonal boron nitride layer.
AB  - The Ullmann reaction is being widely adopted as a strategy for on-surface organic
      synthesis. Herein, we investigated the Ullmann reaction on a hexagonal boron
      nitride (h-BN) layer grown on an Ni(111) substrate using scanning tunneling
      microscopy (STM). We explored the catalytic activity of Cu and Pd atoms dosed
      with the molecular precursors. We found that the dispersed atoms of both metals
      efficiently catalyze the reaction, but lead to different reaction paths.

PMID- 27709167
TI  - 2D materials for renewable energy storage devices: Outlook and challenges.
AB  - Scientists are looking for cost-effective, clean and durable alternative energy
      devices. Superior charge storage devices can easily meet the demands of our daily
      needs. In this respect, a material with suitable dimensions for charge storage
      devices has been considered to be very important. Improved performance of charge
      storage devices has been derived from whole-body participation and the best are
      from 2D materials, which provide a viable and acceptable solution.

PMID- 27709166
TI  - FeMnO3: a high-performance Li-ion battery anode material.
AB  - In this communication, FeMnO3 particles were prepared and evaluated as an anode
      material for Li ion batteries. This electrode shows high capacity, excellent rate
      capability, and good cycling stability (984 mA h g-1 at 1.0 A g-1 after 500
      cycles). Moreover, the Li storage mechanism is studied.

PMID- 27709168
TI  - An efficient construction of N,N-bicyclic pyrazolidinones comprising
      enaminonitriles via asymmetric [3+2] cycloaddition.
AB  - The first thiourea catalysed asymmetric [3+2] cycloaddition reaction between
      azomethine imines and malanonitriles was developed. Using this novel synthetic
      strategy, hybrid molecules containing N,N-bicyclic pyrazolidinones fused with
      enaminonitriles were synthesized in good yields with excellent
      enantioselectivities (up to 98% ee).

PMID- 27709169
TI  - Synthesis and characterization of a homogeneous and silica supported homoleptic
      cationic tungsten(vi) methyl complex: application in olefin metathesis.
AB  - A method for the synthesis of a homogeneous cationic tungsten(vi)pentamethyl
      complex [(WMe5)+(C6F5)3BMe-] from neutral tungstenhexamethyl (WMe6) and a silica
      supported cationic tungstentetramethyl complex [([triple bond, length as m
      dash]Si-O-)WMe4+ (C6F5)3BMe-] from a neutral silica supported tungstenpentamethyl
      complex [([triple bond, length as m-dash]Si-O-)WMe5] is described. In both cases
      a direct demethylation using the B(C6F5)3 reagent was used. The aforesaid
      complexes were characterized by liquid or solid state NMR spectroscopy.
      Interestingly, the homogeneous cationic complex [(WMe5)+(C6F5)3BMe-] shows
      moderate activity whereas the supported cationic complex [([triple bond, length
      as m-dash]Si-O-)WMe4+(C6F5)3BMe-] exhibits good activity in olefin metathesis
      reactions.

PMID- 27709171
TI  - A comparative study of graphite electrodes using the co-intercalation phenomenon
      for rechargeable Li, Na and K batteries.
AB  - Here, we demonstrate that graphite can serve as a versatile electrode for various
      rechargeable battery types by reversibly accommodating solvated alkali ions (such
      as K, Na, and Li) through co-intercalation in its galleries. The co-intercalation
      of alkali ions is observed to occur via staging reactions. Notably, their
      insertion behaviors, including their specific capacity, are remarkably similar
      regardless of the alkali ion species despite the different solubility limits of
      K, Na, and Li ions in graphite. Nevertheless, the insertion potentials of the
      solvated alkali ions differ from each other and are observed to be correlated
      with the interlayer distance in the intercalated graphite gallery.

PMID- 27709170
TI  - Single molecular tuning of the charge balance in blue-emitting iridium dendrimers
      for efficient nondoped solution-processed phosphorescent OLEDs.
AB  - The single molecular tuning of charge balance has been demonstrated here by
      integrating a p-type dendron, an n-type dendron and a blue emissive Ir core into
      one dendritic platform. Compared with the commonly used physical blending, not
      only can the charge balance be well tailored, but also the intrinsic phase
      separation can be successfully eliminated in such developed single molecular
      systems (B-TCz2TPO1 and B-TCz1TPO2). As a consequence, their corresponding
      nondoped solution-processed PhOLEDs achieve more than doubled external quantum
      efficiencies accompanied by a negligible efficiency roll-off.

PMID- 27709172
TI  - Copper(i)-catalysed oxidative C-N coupling of 2-aminopyridine with terminal
      alkynes featuring a C[triple bond, length as m-dash]C bond cleavage promoted by
      visible light.
AB  - Facile visible-light promoted copper-catalyzed aerobic oxidative C-N coupling
      between 2-aminopyridine and terminal alkynes at room temperature via C[triple
      bond, length as m-dash]C triple bond cleavage is described. This reaction allows
      direct synthesis of biologically important pyridyl amides by utilization of
      commercially available starting materials without the need for bases/external
      oxidants.

PMID- 27709174
TI  - Highly hierarchical porous structures constructed from NiO nanosheets act as Li
      ion and O2 pathways in long cycle life, rechargeable Li-O2 batteries.
AB  - Flower-like NiO with a highly hierarchical porous structure was synthesized and
      used as a cathode material for Li-O2 batteries. The disordered porous structure
      and specific pathways for O2 and Li ions led to an outstanding cycling
      performance over 80 cycles at a high current density of 200 mA g-1.

PMID- 27709173
TI  - Fluorogenic bidirectional displacement probe-based real-time isothermal DNA
      amplification and specific visual detection of products.
AB  - A unique fluorogenic nucleic acid probe has been devised, called the fluorogenic
      bidirectional displacement probe, which can serve as both the primer and the
      signal indicator of amplification products for the development of the real-time
      isothermal DNA amplification and its visual detection of products with high
      sensitivity and specificity.

PMID- 27709176
TI  - Exploration of K2Ti8O17 as an anode material for potassium-ion batteries.
AB  - Novel K2Ti8O17 is successfully fabricated via a facile hydrothermal method
      combined with a subsequent annealing treatment and further evaluated as an anode
      material for potassium-ion batteries for the first time. This study may provide a
      broader vision into developing anode materials for potassium-ion batteries.

PMID- 27709175
TI  - Noble-metal loading reverses temperature dependent photocatalytic hydrogen
      generation in methanol-water solutions.
AB  - Co-catalysts and sacrificing reagents are important components in artificial
      photocatalytic processes. Here we demonstrate that noble-metal loading reverses
      the temperature dependent photocatalytic activity trends of photocatalytic
      hydrogen (H2) generation with methanol as a sacrificing reagent. This finding
      suggested that visible and infrared light can enhance photocatalytic H2
      generation via a heat effect over noble-metal/photocatalysts.

PMID- 27709177
TI  - A novel membrane with heterogeneously functionalized nanocrystal layers
      performing blood separation and sensing synchronously.
AB  - A novel membrane with heterogeneously functionalized nanocrystal layers was
      designed to synchronously perform in situ blood separation and sensing for the
      extraction of pure serum without any blood cells and fibrinogen by size sieving,
      and simultaneously realizing the electrochemical analysis of various
      physiological indexes.

PMID- 27709178
TI  - Rhodium-catalyzed transformation of heteroaryl aryl ethers into heteroaryl
      fluorides.
AB  - A rhodium complex catalyzed the conversion of the C-O bond of heteroaryl aryl
      ethers to the C-F bond. The reaction of (4-chlorophenylthio)pentafluorobenzene
      with heteroaryl aryl ethers provided heteroaryl fluorides and heteroaryl (4
      chlorophenylthio)tetrafluorophenyl ethers; this involved the cleavage of a single
      heteroaryl C-O bond under equilibrium conditions. The reaction of heteroaryl aryl
      ethers with 2-fluorobenzothiazole in which two heteroaryl and aryl C-O bonds were
      cleaved provided heteroaryl fluorides and aryl fluorides. The reactions were
      applicable to five-membered and six-membered heteroaryl aryl ethers and also to
      diaryl ethers possessing one or two electron-withdrawing groups.

PMID- 27709179
TI  - Host-guest chemistry in two-dimensional supramolecular networks.
AB  - Nanoporous supramolecular networks physisorbed on solid surfaces have been
      extensively used to immobilize a variety of guest molecules. Host-guest chemistry
      in such two-dimensional (2D) porous networks is a rapidly expanding field due to
      potential applications in separation technology, catalysis and nanoscale
      patterning. Diverse structural topologies with high crystallinity have been
      obtained to capture molecular guests of different sizes and shapes. A range of
      non-covalent forces such as hydrogen bonds, van der Waals interactions,
      coordinate bonds have been employed to assemble the host networks. Recent years
      have witnessed a surge in the activity in this field with the implementation of
      rational design strategies for realizing controlled and selective guest capture.
      In this feature article, we review the development in the field of surface
      supported host-guest chemistry as studied by scanning tunneling microscopy (STM).
      Typical host-guest architectures studied on solid surfaces, both under ambient
      conditions at the solution-solid interface as well as those formed at the
      ultrahigh vacuum (UHV)-solid interface, are described. We focus on isoreticular
      host networks, hosts functionalized pores and dynamic host-guest systems that
      respond to external stimuli.

PMID- 27709180
TI  - A six-step total synthesis of alpha-thujone and d6-alpha-thujone, enabling facile
      access to isotopically labelled metabolites.
AB  - The short synthesis of alpha-thujone relies on the functionalization of the
      readily available dimethylfulvene. Furthermore, the three main metabolites of the
      natural product were also synthesized. Since d6-acetone can be used as a starting
      material, the route developed allows for the facile incorporation of isotopic
      labels which are required for detecting and quantifying trace amounts via GC/MS
      analysis.

PMID- 27709182
TI  - Activation of SO2 by [Zn(Cp*)2] and [(Cp*)ZnI-ZnI(Cp*)].
AB  - Interesting reactivity was observed in reactions of SO2 with [Zn(Cp*)2] and
      [(Cp*)ZnI-ZnI(Cp*)]. These reactions proceeded with insertion of SO2 into the Zn
      C bonds. Spectacularly, the lability of the C-S bond in the O2SCp* ligands led to
      the thermal decomposition of [Zn(O2SCp*)2(tmeda)] to afford [Zn2(MU-SO3)(MU
      S2O4)(tmeda)2].

PMID- 27709181
TI  - Aptamer-based FRET nanoflares for imaging potassium ions in living cells.
AB  - Due to the effective properties of the FRET signal and K+-sensitive recognition
      of G-quadruplex, aptamer-based FRET nanoflares were developed to sense
      intracellular potassium ions.

PMID- 27709183
TI  - MOF-aminoclay composites for superior CO2 capture, separation and enhanced
      catalytic activity in chemical fixation of CO2.
AB  - We delineate the growth and stabilization of ultra-small (2-3 nm)
      {Cu3(BTC)2(H2O)2.xH2O} MOF nanoparticles on a 2D layered aminoclay template. The
      composite shows significant CO2 uptake (5.35 mmol g-1 at 298 K, 1 bar; 46% higher
      than pristine bulk MOF), superior CO2 separation efficiency from CO2/N2 and
      CO2/CH4 mixtures and higher catalytic proficiency for chemical fixation of CO2
      into cyclic carbonates.

PMID- 27709184
TI  - End-capping of amphiphilic nanotubes with phospholipid vesicles: impact of the
      phospholipid on the cap formation and vesicle loading under osmotic conditions.
AB  - Soft amphiphilic nanotubes are capped with vesicles comprised of either overall
      neutral, zwitterionic phospholipids, or those that carry a net charge. The phase
      transition temperature of the zwitterionic phospholipids plays a crucial role in
      the phase separation that leads to the end-capped nanotubes. The cationic vesicle
      caps can be loaded into the nanotubes via osmosis whereas the anionic vesicle
      caps are stable under hyper-osmotic conditions. Furthermore, no additional salt
      needs to be added for the cationic vesicle caps to induce the loading of the
      vesicles into the nanotubes due to the presence of counterions.

PMID- 27709186
TI  - Hydrogen release reactions of Al-based complex hydrides enhanced by vibrational
      dynamics and valences of metal cations.
AB  - Hydrogen release from Al-based complex hydrides composed of metal cation(s) and
      [AlH4]- was investigated using inelastic neutron scattering viewed from
      vibrational dynamics. The hydrogen release followed the softening of
      translational and [AlH4]- librational modes, which was enhanced by vibrational
      dynamics and the valence(s) of the metal cation(s).

PMID- 27709185
TI  - Assessing the intracellular fate of rhodium(ii) complexes.
AB  - Rhodium(ii)-fluorophore conjugates have strong rhodium-based fluorescence
      quenching that can be harnessed to report on a conjugate's cellular uptake and
      the intracellular decomposition rate. Information gleened from this study allowed
      the design of an improved STAT3 metalloinhibitor.

PMID- 27709187
TI  - Cooperative self-assembly of porphyrins with polymers possessing bioactive
      functions.
AB  - Natural porphyrin derivatives possess many interesting functions in biological
      systems. They are integrated into proteins that are essential for biological
      activities. Many efforts have been dedicated to mimic the microenvironment and
      augment the function of porphyrin/protein scaffolds. To achieve such goals, self
      assembly has become one of the popular methods to construct porphyrin/protein
      mimicking materials owing to its various choices of building blocks and a simple
      preparation process over chemical modification. Desirable characteristics of
      building blocks for protein mimicking include high molecular weight, predictable
      conformations in solution, and appropriate functional residuals. With these aims
      in mind, polymers are ideal candidates due to their multiple-level hierarchies
      derived from their chemical and spatial structures. In this review, design
      strategies for the cooperative self-assembly of porphyrins with polymers and the
      main efforts towards the implementation of porphyrin/polymer assembly for
      biomimetic composites with bioactive functions will be addressed.

PMID- 27709188
TI  - Grafting of gold onto spin-crossover nanoparticles: SCO@Au.
AB  - Nanoparticles of gold were successfully grafted onto nanoparticles of a 1D
      polymeric spin-crossover material leading to singular SCO@Au hybrid particles.
      The result is equally obtained using a large range of gold-particle sizes, from 4
      to 45 nm, which first allows definition of the best experimental conditions,
      notably in terms of gold-particle concentration, and then demonstrates the
      robustness and the efficiency of the method.

PMID- 27709189
TI  - Screening for positive electrodes for magnesium batteries: a protocol for studies
      at elevated temperatures.
AB  - The well-known all phenyl complex (APC) electrolyte for magnesium batteries is
      studied for the first time at high temperature using tetraglyme as a solvent.
      Combined with a molybdenum current collector, this enables the examination of
      positive electrode materials for Mg batteries at temperatures as high as 180 
      degrees C and up to 2 V vs. Mg, allowing discovery of the auspicious properties
      of CuS as a conversion cathode.

PMID- 27709190
TI  - Silicon carbon nanoparticles-based chemiluminescence probe for hydroxyl radical
      in PM2.5.
AB  - A new SiC nanoparticles (SiC NPs)-based chemiluminescence (CL) probe for
      selective and sensitive detecting of OH has been developed. The radiative
      recombination of OH-injected holes and electrons in the SiC NPs accounts for the
      CL phenomenon. Furthermore, the as-developed CL probe has been successfully
      applied to detect OH in PM2.5.

PMID- 27709191
TI  - Naphthalene-fused BODIPY near-infrared dye as a stable contrast agent for in vivo
      photoacoustic imaging.
AB  - Photoacoustic imaging (PAI) has emerged as an advantageous modality with high
      resolution and deep tissue penetration. However, its application is limited by
      the lack of available contrast agents. In this work, we report the synthesis of a
      naphthalene fused BODIPY dimer Na-BD, and the impact of the electronic structure
      on the oxidative cyclo-dehydrogenation process was systematically studied. Na-BD
      exhibited intense NIR absorption, much better photo-stability and higher PA
      activity compared to commercial ICG dye, which makes it an excellent contrast
      agent for PAI. Moreover, the in vivo PAI studies based on Na-BD loaded BSA
      nanoparticles were carried out and they demonstrated a significant passive
      targeting capacity by exploiting the enhanced permeability and retention effect
      in the tumor region.

PMID- 27709192
TI  - Facile synthesis of hierarchical dendrite-like structure iron layered double
      hydroxide nanohybrids for effective arsenic removal.
AB  - The highly dispersed iron layered double hydroxide (Fe-LDH) nanoplates supported
      on sepiolite (SEP) nanofibers have been successfully prepared via in situ co
      precipitation of an iron salt precursor. The as-obtained hierarchical dendrite
      like Fe-LDH/SEPs possess high specific area, and exhibit excellent removal
      ability for arsenic, demonstrating promising potential in environment
      applications.

PMID- 27709193
TI  - A facile approach for the fabrication of 2D supermicelle networks.
AB  - A novel and facile approach to fabricating well-organized macroscopic 2D networks
      of cylindrical micelles is reported, based on transfer printing and thermal
      welding of aligned supramolecular micelles of block copolymers. This versatile
      approach provides a new strategy for fabricating functional 2D superstructures
      with a higher level of order.

PMID- 27709194
TI  - Functionalized carbon nanotubes and graphene-based materials for energy storage.
AB  - Carbon nanotubes (CNTs) or graphene-based nanomaterials functionalized by
      different strategies have attracted great attention for energy storage due to
      their large specific surface area, high conductivity, and good mechanical
      properties. This feature article presents an overview of the recent progress in
      the functionalization of CNTs and graphene-based materials for energy storage
      applications in supercapacitors and batteries, along with challenges and
      perspectives in this exciting field.

PMID- 27709195
TI  - Shape and phase evolution from CsPbBr3 perovskite nanocubes to tetragonal
      CsPb2Br5 nanosheets with an indirect bandgap.
AB  - Tetragonal CsPb2Br5 nanosheets were obtained by an oriented attachment of
      orthorhombic CsPbBr3 nanocubes, involving a lateral shape evolution from
      octagonal to square. Meanwhile, the experimental results, together with DFT
      simulation results, indicated that the tetragonal CsPb2Br5 is an indirect bandgap
      semiconductor that is PL-inactive with a bandgap of 2.979 eV.

PMID- 27709197
TI  - Chiral signs of TPPS co-assemblies with chiral gelators: role of molecular and
      supramolecular chirality.
AB  - A dianionic tetrakis(4-sulfonatophenyl)porphyrin (TPPS) self-assembled into J
      aggregates when it co-assembled with a chiral cationic amphiphile via
      supramolecular gelation. The chiral signs of TPPS J aggregates followed the
      supramolecular chirality of amphiphilic assemblies rather than the molecular
      chirality of the amphiphile.

PMID- 27709196
TI  - Nebraska Red: a phosphinate-based near-infrared fluorophore scaffold for chemical
      biology applications.
AB  - A series of novel phosphinate-based dyes displaying near-infrared fluorescence
      (NIR) are reported. These dyes exhibit remarkable photostability and brightness.
      The phosphinate functionality is leveraged as an additional reactive handle in
      order to tune cell permeability as well as provide a proof-of-principle for a
      self-reporting small molecule delivery vehicle.

PMID- 27709198
TI  - Fluorescent vesicles formed by simple surfactants induced by oppositely-charged
      carbon quantum dots.
AB  - We show for the first time that stable fluorescent vesicles can be constructed by
      mixing oppositely-charged carbon quantum dots (CQDs) and simple surfactants in
      water, and can be potentially used as a new generation of biomarkers and drug
      delivery vehicles.

PMID- 27709199
TI  - Helix-helix inversion of an optically-inactive pi-conjugated foldamer triggered
      by concentration changes of a single enantiomeric guest leading to a change in
      the helical stability.
AB  - A preferred-handed helicity induced in an optically-inactive
      poly(phenyleneethynylene)-based foldamer bearing carboxylic acid pendants upon
      complexation with a single enantiomeric diamine was subsequently inverted into
      the opposite helix upon further addition of the diamine, accompanied by a
      remarkable change in the stability of the helices.

PMID- 27709200
TI  - PicoGreen: a better amyloid probe than Thioflavin-T.
AB  - PicoGreen, a cyanine based ultrafast molecular rotor, shows high affinity towards
      amyloid fibrils and scores a much better sensitivity than Thioflavin-T, a gold
      standard probe for amyloid fibrils. Detailed spectroscopic and molecular docking
      studies have been performed to understand the mode of interaction between
      PicoGreen and amyloid fibrils.

PMID- 27709201
TI  - Catalytic CO2-to-CO conversion in water by covalently functionalized carbon
      nanotubes with a molecular iron catalyst.
AB  - The covalent grafting of an Fe porphyrin on carbon nanotubes led to efficient
      electroreduction of CO2 into CO in water (pH 7.3). CO was obtained with high
      selectivity and turnover at 0.5 V overpotential. The grafting strategy may be
      further extended to various conductive and semi-conductive surfaces.

PMID- 27709202
TI  - Efficient photoluminescent thin films consisting of anchored hybrid perovskite
      nanoparticles.
AB  - Methylammonium lead bromide nanoparticles are synthetized with a new ligand (11
      aminoundecanoic acid hydrobromide) by a non-template method. Upon dispersion in
      toluene they show a remarkable photoluminescence quantum yield of 80%. In
      addition, the bifunctional ligand allows anchoring of the nanoparticles on a
      variety of conducting and semiconducting surfaces, showing bright
      photoluminescence with a quantum yield exceeding 50%. This opens a path for the
      simple and inexpensive preparation of multilayer light-emitting devices.

PMID- 27709203
TI  - Defect-induced ripening of zeolitic-imidazolate framework ZIF-8 and its
      implication to vapor-phase membrane synthesis.
AB  - We report for the first time that ZIF-8 crystals undergo an Ostwald-ripening-like
      process without degradation in the presence of a ligand vapor. The ripening
      process is dependent on the defect density of the crystals: the more defective
      the more amenable to the ripening. The process was adapted to synthesize ultra
      thin ZIF-8 membranes by vapor-phase secondary growth.

PMID- 27709204
TI  - Cu-Catalyzed hydrophosphorylative ring opening of propargyl epoxides: highly
      selective access to 4-phosphoryl 2,3-allenols.
AB  - A novel CuI-catalyzed cross-coupling of propargyl epoxides with P(O)H compounds
      is disclosed. The reaction proceeded efficiently under mild conditions to give 4
      phosphoryl 2,3-allenols in good to high yields with excellent selectivity. The
      utility of the products was demonstrated and a plausible mechanism was also
      proposed.

PMID- 27709205
TI  - para-Selective C-H bond functionalization of iodobenzenes.
AB  - Selective C-H bond activation and functionalization is an invaluable and eco
      friendly tool for new chemical bond construction. Recently, great progress has
      been made in the highly selective ortho- and meta-C-H bond functionalization of
      arene derivatives. In contrast, the remote para-C-H bond functionalization still
      remains a challenge. Herein, an oxidation-induced strategy for para-selective C-H
      bond functionalization of iodobenzenes towards the synthesis of various useful
      asymmetric diaryl ethers was demonstrated. This strategy not only provides a
      novel method for para-C-H bond functionalization, but also proposes a general
      idea for the development of new, highly selective para-C-H functionalization
      reactions.

PMID- 27709206
TI  - Iron-catalyzed oxidative sp3 carbon-hydrogen bond functionalization of 3,4
      dihydro-1,4-benzoxazin-2-ones.
AB  - A novel and efficient iron-catalyzed sp3 carbon-hydrogen bond functionalization
      of benzoxazinone derivatives has been developed. For the first time, benzoxazin-2
      ones were used as substrates in an oxidative dehydrogenative coupling reaction.
      The experiments were performed under mild reaction conditions to construct alkyl
      aryl C(sp3)-C(sp2) bonds. The application of this method to the gram-scale
      synthesis of natural product cephalandole A has been accomplished in a 3-step
      sequence. A plausible one electron oxidation involved mechanism is proposed.

PMID- 27709207
TI  - Size selectable nanoparticle assemblies with magnetic anisotropy tunable across
      the superparamagnetic to ferromagnetic range.
AB  - We present a novel approach for the preparation of magnetic nanoparticle clusters
      of controlled size and selectable magnetic anisotropy, which provides materials
      with properties selectable for biomedical applications and as components in
      magnetically responsive nanocomposites. The assembly process is based on a ligand
      desorption strategy and allows selection of nanoparticle size and temporal
      control over final cluster size. Detailed NMR analysis of the suspensions
      pinpoints the role of particle size in controlling the interparticle
      interactions, within the clusters, which effectively determine the anisotropy.
      Colloidal interaction modelling confirms this interpretation and provides a means
      to predict both colloidal stability and magnetic anisotropy.

PMID- 27709208
TI  - Hierarchical porous carbon materials prepared using nano-ZnO as a template and
      activation agent for ultrahigh power supercapacitors.
AB  - Hierarchical porous carbon materials with high surface areas and a localized
      graphitic structure were simply prepared from sucrose using nano-ZnO as a hard
      template, activation agent and graphitization catalyst simultaneously, which
      exhibit an outstanding high-rate performance and can endure an ultrafast scan
      rate of 20 V s-1 and ultrahigh current density of 1000 A g-1.

PMID- 27709209
TI  - The role of steric hindrance in the intramolecular oxidative aromatic coupling of
      pyrrolo[3,2-b]pyrroles.
AB  - The presence of steric hindrance triggers different reaction pathways in the
      intramolecular oxidative aromatic coupling of tetraaryl-pyrrolo[3,2-b]pyrroles
      and leads to the formation of a fluorene moiety and a new cationic pi-system
      linked together by a spiro carbon atom. Computational studies elegantly
      rationalized these results. These previously unknown functional dyes emit red
      light with reasonable efficiency.

PMID- 27709210
TI  - A robust and quantitative assay platform for multiplexed, high throughput
      screening of protein kinase inhibitors.
AB  - We present a new platform for multiplexed protein kinase activity assay using
      TiO2 decorated graphene oxide (GO), which is applicable to high throughput
      inhibitor screening. On the basis of the strong affinity of TiO2 for the
      phosphate group and the fluorescence quenching capability of GO, phosphorylation
      of substrates by protein kinases was quantitatively measured in a short time.

PMID- 27709211
TI  - High-efficiency water collection on biomimetic material with superwettable
      patterns.
AB  - A superhydrophilic surface with two superhydrophobic circular patterns was
      fabricated via a simple and rapid route, showing outstanding fog harvesting
      properties with a water collection rate (WCR) of 1316.9 mg h-1 cm-2. Water
      collection can be repeated on the sample 10 times without obvious change in the
      WCR.

PMID- 27709212
TI  - A high performance three-dimensional thiophene-annulated perylene dye as an
      acceptor for organic solar cells.
AB  - A high performance three-dimensional (3D) thiophene-annulated perylene dye,
      namely tetra-PBI-S, was designed and synthesized. The appropriate LUMO level,
      balanced carrier mobilities and favourable phase separation make tetra-PBI-S
      based solar cells show a much higher power conversion efficiency (PCE) of 6.2%
      than tetra-PBI based solar cells with a PCE of 3.6%.

PMID- 27709213
TI  - Manifesting the sergeants-and-soldiers principle in coadsorber induced homochiral
      polymorphic assemblies at the liquid/solid interface.
AB  - We systematically studied the operation of coadsorber-induced surface chirality
      in a series of enantiomeric surface supramolecular assemblies. The correlation of
      chiral amplification degree with the proportion of enantiomeric interaction in
      the total intermolecular interaction is deduced.

PMID- 27709214
TI  - Mechanistic analysis of aliphatic beta-lactones in Vibrio harveyi reveals a
      quorum sensing independent mode of action.
AB  - N-Acylhomoserine lactones are autoinducers of quorum sensing (QS) in Gram
      negative bacteria. We exploit here the role of structurally related beta-lactones
      in the inhibition of Vibrio harveyi bioluminescence and identify a derivative
      with nanomolar potency. Surprisingly, QS was not affected and combined
      proteomic/biochemical studies revealed insights into the cellular mode of action.

PMID- 27709215
TI  - Electrocatalytic water oxidation by a molecular cobalt complex through a high
      valent cobalt oxo intermediate.
AB  - Biuret-modified tetraamidomacrocyclic cobalt complex [CoIII-bTAML]- is shown to
      catalyze electrochemical water oxidation at basic pH leading to the formation of
      O2. Electrochemical and spectroscopic studies indicate a high valent cobalt oxo
      intermediate isoelectronic to CoV(O) as the active oxidant. The kinetic isotope
      effect of 8.63 indicates an atom proton transfer mechanism.

PMID- 27709216
TI  - Chiral templating of alumina nanofilms by the atomic layer deposition process.
AB  - In this communication, we describe the synthesis of new chiral alumina nanofilms
      and surfaces. Our method is based on chiral templating of alumina nanofilms by
      cellulose microfibers using the atomic layer deposition process. The chiral
      nature of the alumina nanofilms was characterized by a variety of techniques,
      such as quartz crystal microbalance, chiral circular-dichroism adsorption, chiral
      high-performance liquid chromatography and cyclic voltammetry measurements.

PMID- 27709217
TI  - From nano- to macro-engineering of oxide-encapsulated-nanoparticles for harsh
      reactions: one-step organization via cross-linking molecules.
AB  - A strategy of "macro-micro-nano" organization is reported for embedding oxide
      encapsulated-nanoparticles onto monolithic substrates in one-step with the aid of
      molecularly defined cross-linking agents. Such catalysts, with enhanced heat/mass
      transfer and high permeability, are qualified for several harsh reaction
      processes such as CH4/VOC abatement, gas-phase hydrogenation of dimethyl oxalate
      and oxidative dehydrogenation of ethane.

PMID- 27709218
TI  - The role of counter-anions in the kinetics and chirality of porphyrin J
      aggregates.
AB  - Kinetics of the growth of TPPS4 porphyrin J-aggregates slow down in the order
      H2SO4 > HCl > HBr > HNO3 > HClO4, in agreement with the Hofmeister series. The
      rate constants and the extent of chirality correlate with the structure-making or
      breaking abilities of the different anions with respect to the hydrogen bonding
      network of the solvent.

PMID- 27709219
TI  - A concise gram-scale synthesis of ht-13-A via a rhodium-catalyzed intramolecular
      C-H activation reaction.
AB  - The enantioselective total synthesis of the 3,4-fused indole alkaloid ht-13-A has
      been achieved. The synthesis features a zinc-mediated propargylation, a rhodium
      catalyzed intramolecular C-H activation reaction, and a methylamine-mediated
      cyclization. This concise and efficient synthetic approach can be applied for the
      gram-scale synthesis of ht-13-A.

PMID- 27709220
TI  - Nanospring electrochemical lithography (NEL): noble metal nanohelices.
AB  - We report three-dimensional helical Au nanostructures using anodized aluminum
      oxide (AAO) and the embedded Pd nanosprings, serving as primary and secondary
      templates, respectively. The resulting Au nanohelices exhibit strong SERS signals
      due to the electromagnetic field enhancement originating from the helical
      morphology; this behavior is seemingly analogous to that of a nano-gap enhancer.
      Nanospring electrochemical lithography (NEL) represents a new method for
      synthesizing complex helical nanostructures and has potential for application in
      materials science.

PMID- 27709221
TI  - Evaluation of an intra-articular synthetic ligament for treatment of cranial
      cruciate ligament disease in dogs: a six-month prospective clinical trial.
AB  - OBJECTIVE: Evaluate the short-term outcomes of a novel synthetic ligament for
      treatment of naturally occurring canine cranial cruciate ligament disease. STUDY
      DESIGN: Prospective clinical study. ANIMALS: Dogs with unilateral cranial
      cruciate ligament disease (n = 50). METHODS: Patient parameters evaluated
      included a five-point lameness score, evaluation of craniocaudal stifle
      instability, and radiographic findings over 24 weeks. Any postoperative
      complications were recorded. RESULTS: Thirty-four out of 42 dogs experienced
      significant improvements in lameness between the preoperative and 24 week time
      points. Lameness scores in those dogs improved significantly at all measured time
      intervals after postoperative week 2. Recurrence of stifle instability increased
      significantly over the study period from immediate postoperative measurements.
      Cranial drawer recurred in seven out of 42 of dogs by week 4 and 18/42 by week
      24. Implant changes were not noted between the immediate and six-month
      postoperative radiographs except where complications occurred. Overall, 25 dogs
      experienced a total of 32 complications (22 major and 10 minor). Sixteen dogs had
      major complications, and nine had minor complications. CONCLUSION: The procedure
      was generally effective at improving lameness scores, but did not consistently
      maintain postoperative stifle stability and had an unacceptably high complication
      rate. This synthetic ligament procedure cannot be recommended for use in its
      current form.

PMID- 27709222
TI  - Pullout strength of monocortical and bicortical screws in metaphyseal and
      diaphyseal regions of the canine humerus.
AB  - OBJECTIVE: Monocortical screws are commonly employed in locking plate fixation,
      but specific recommendations for their placement are lacking and use of short
      monocortical screws in metaphyseal bone may be contraindicated. Objectives of
      this study were to evaluate axial pullout strength of two different lengths of
      monocortical screws placed in various regions of the canine humerus compared to
      bicortical screws, and to derive cortical thickness and bone density values for
      those regions using quantitative computed tomography analysis (QCT). METHODS: The
      QCT analysis was performed on 36 cadaveric canine humeri for six regions of
      interest (ROI). A bicortical, short monocortical, or 50% transcortical 3.5 mm
      screw was implanted in each ROI and axial pullout testing was performed. RESULTS:
      Bicortical screws were stronger than monocortical screws in all ROI except the
      lateral epicondylar crest. Short monocortical metaphyseal screws were weaker than
      those placed in other regions. The 50% transcortical screws were stronger than
      the short monocortical screws in the condyle. A linear relationship between screw
      length and pullout strength was observed. CLINICAL SIGNIFICANCE: Cortical
      thickness and bone density measurements were obtained from multiple regions of
      the canine humerus using QCT. Use of short monocortical screws may contribute to
      failure of locking plate fixation of humeral fractures, especially when placed in
      the condyle. When bicortical screw placement is not possible, maximizing
      monocortical screw length may optimize fixation stability for distal humeral
      fractures.

PMID- 27709223
TI  - Tibial plateau levelling osteotomy in eleven cats with cranial cruciate ligament
      rupture.
AB  - OBJECTIVE: To report the surgical procedure, intra- and postoperative
      complications, and short-term follow-up of tibial plateau levelling osteotomy
      (TPLO) in feline patients with cranial cruciate ligament (CrCL) rupture using a
      2.0 or 2.4 mm Synthes(r) TPLO plate. STUDY DESIGN: Prospective study. MATERIAL
      AND METHODS: Eleven cats with a CrCL rupture were included in the study.
      Inspection of intra-articular structures was carried out via arthroscopy or
      arthrotomy. Each patient was re-examined one and 10 days after surgery.
      Orthopaedic examination and follow-up radiographs were obtained four to 12 weeks
      postoperatively. RESULTS: Two meniscopathies and one partial CrCL rupture were
      detected. Minor intra-operative complications occurred in five cats (suboptimal
      positioning of the plate [n = 3], proximal fibular fracture [n = 1], a visible
      osteotomy gap [n = 1]). Postoperatively, minor complications were detected in
      three cats (mild patellar desmitis [n = 2], superficial wound infection [n = 1]).
      No additional surgical reintervention, graded as major complication, was
      necessary. Four to eight weeks postoperatively, all cats showed no to mild
      intermittent lameness. Complete bone union was apparent within four to 12 weeks.
      Owners reported a high level of comfort and mobility during the last follow-up.
      CONCLUSION: The preliminary results of this study support the use of TPLO in
      cats, but larger case numbers are needed to evaluate its practicability, as well
      as long-term outcome (>1 year), especially evaluating the development and the
      clinical relevance of osteoarthritis.

PMID- 27709224
TI  - The effect of intramedullary pin size and plate working length on plate strain in
      locking compression plate-rod constructs under axial load.
AB  - OBJECTIVE: To investigate the effect of intramedullary pin size and plate working
      length on plate strain in locking compression plate-rod constructs. METHODS: A
      synthetic bone model with a 40 mm fracture gap was used. Locking compression
      plates with monocortical locking screws were tested with no pin (LCP-Mono) and
      intramedullary pins of 20% (LCPR-20), 30% (LCPR-30) and 40% (LCPR-40) of
      intramedullary diameter. Two screws per fragment modelled a long (8-hole) and
      short (4-hole) plate working length. Strain responses to axial compression were
      recorded at six regions of the plate via three-dimensional digital image
      correlation. RESULTS: The addition of a pin of any size provided a significant
      decrease in plate strain. For the long working length, LCPR-30 and LCPR-40 had
      significantly lower strain than the LCPR-20, and plate strain was significantly
      higher adjacent to the screw closest to the fracture site. For the short working
      length, there was no significant difference in strain across any LCPR constructs
      or at any region of the plate. Plate strain was significantly lower for the short
      working length compared to the long working length for the LCP-Mono and LCPR-20
      constructs, but not for the LCPR-30 and LCPR-40 constructs. CLINICAL
      SIGNIFICANCE: The increase in plate strain encountered with a long working length
      can be overcome by the use of a pin of 30-40% intramedullary diameter. Where
      placement of a large diameter pin is not possible, screws should be placed as
      close to the fracture gap as possible to minimize plate strain and distribute it
      more evenly over the plate.

PMID- 27709225
TI  - Increased circulating resistin is associated with insulin resistance, oxidative
      stress and platelet activation in type 2 diabetes mellitus.
AB  - Resistin is an adipokine that promotes inflammation and insulin resistance by
      targeting several cells including platelets. We hypothesised that in type 2
      diabetes (T2DM), resistin may foster in vivo oxidative stress, thromboxane
      dependent platelet activation and platelet-derived inflammatory proteins release,
      key determinants of atherothrombosis. A cross-sectional comparison of circulating
      resistin, sCD40L, as a marker of platelet-mediated inflammation, asymmetric
      dimethylarginine (ADMA), endothelial dysfunction marker, Dickkopf (DKK)-1,
      reflecting the inflammatory interaction between platelets and endothelial cells,
      and urinary 8-iso-PGF2alpha and 11-dehydro-TxB2, reflecting in vivo lipid
      peroxidation and platelet activation, respectively, was performed between 79 T2DM
      patients and 30 healthy subjects. Furthermore, we investigated the effects of the
      alpha-glucosidase inhibitor acarbose and the PPARgamma agonist rosiglitazone,
      targeting hyperglycaemia or insulin resistance, versus placebo, in 28 and 18 T2DM
      subjects, respectively. Age- and gender-adjusted serum resistin levels were
      significantly higher in patients than in controls. HOMA (beta=0.266, p=0.017) and
      11-dehydro-TXB2 (beta=0.354, p=0.002) independently predicted resistin levels. A
      20-week treatment with acarbose was associated with significant reductions
      (p=0.001) in serum resistin, DKK-1, urinary 11-dehydro-TXB2 and 8-iso-PGF2alpha
      with direct correlations between the change in serum resistin and in other
      variables. A 24-week rosiglitazone treatment on top of metformin was associated
      with significant decreases in resistin, DKK-1, 11-dehydro-TXB2 and 8-iso
      PGF2alpha, in parallel with HOMA decrease. In conclusion, resistin, antagonising
      insulin action in part through PPARgamma activation, may favour insulin
      resistance and enhance oxidative stress, endothelial dysfunction and platelet
      activation. The adipokine-platelet interactions may be involved in platelet
      insulin resistance and their consequent pro-aggregatory phenotype in this
      setting.

PMID- 27709226
TI  - Epidemiology of first and recurrent venous thromboembolism in patients with
      active cancer. A population-based cohort study.
AB  - Population studies on the incidence of venous thromboembolism (VTE) in patients
      with active cancer are limited. An observational cohort study was undertaken to
      estimate the incidence of first and recurrent VTE. The source population
      consisted of all patients in the UK Clinical Practice Research Datalink, with
      additional information on hospitalisation and cause of death, between 2001 and
      2011. A cancer-related clinical diagnosis or therapy within the 90 days before or
      after a VTE constituted an active-cancer-associated VTE. Incidence rates of first
      VTE among patients with active cancer and incidence rates of recurrent VTE during
      the 10-year observational period after a first VTE event were estimated.
      Incidence rates of all-cause mortality and age- and gender-specific mortality
      were also calculated. There were 6,592 active-cancer-associated VTEs with a total
      of 112,738 cancer-associated person-years of observation. The incidence rate of
      first VTE in patients with active cancer was 5.8 (95 % confidence interval 5.7
      6.0) per 100 person-years. A first VTE recurrence was observed in 591 patients.
      The overall incidence rate for recurrence was 9.6 (95 % confidence interval 8.8
      10.4) per 100 person-years, with a peak at 22.1 in the first six months.
      Recurrence rates were similar after initial pulmonary embolism and after initial
      deep-vein thrombosis. The mortality risk after VTE was considerable, with 64.5 %
      mortality after one year and 88.1 % after 10 years. VTE in patients with active
      cancer is common and associated with high recurrence and mortality rates. Efforts
      are needed to prevent VTE and reduce recurrence, especially in the first year
      after VTE diagnosis.

PMID- 27709227
TI  - Is Meeting the Recommended Dietary Allowance (RDA) for Protein Related to Body
      Composition among Older Adults?: Results from the Cardiovascular Health of
      Seniors and Built Environment Study.
AB  - OBJECTIVE: Studies suggest protein intake may be associated with lower body
      weight, but protein has also been associated with preservation of lean body mass.
      Understanding the role of protein in maintaining health for older adults is
      important for disease prevention among this population. DESIGN: Cross-sectional
      study of the relationship of dietary protein on body composition. SETTING: New
      York City community centers. PARTICIPANTS: 1,011 Black, White, and Latino urban
      men and women 60-99 years of age. MEASUREMENTS: Protein intake was assessed using
      two interviewer-administered 24-hour recalls, and body composition was assessed
      using bioelectrical impedance analysis (BIA) of fat mass (kg) (FM), fat free mass
      (kg) (FFM), and impedance resistance (Ohms). STATISTICAL ANALYSIS: Indices of FM
      and FFM were calculated by dividing BIA measurements by height squared (m2), and
      percent FFM was calculated by dividing FFM by the sum of FM and FFM. Log linear
      models adjusting for age (continuous), race/ethnicity, education, physical
      activity (dichotomized at the median), hypertension, diabetes, and total calories
      (continuous). RESULTS: Just 33% of women and 50% of men reported meeting the RDA
      for protein. Both fat free mass index (FFMI) and fat mass index (FMI) were
      negatively associated with meeting the RDA for protein (Women: FFMI -1.78 95%CI [
      2.24, -1.33], FMI -4.12 95% CI [-4.82, -3.42]; Men: FFMI -1.62 95% CI [-2.32, 
      0.93] FMI -1.80 95% CI [-2.70, -0.89]). After accounting for confounders, women
      and men consuming at least 0.8 g/kg/day had a 6.2% (95% CI: 5.0%, 7.4%) and a
      3.2% (95% CI 1.1%, 5.3%) higher percent fat free mass, respectively. CONCLUSIONS:
      FFM, FFMI, FM, and FMI were inversely related to meeting the RDA for protein.
      Meeting the RDA for protein of at least 0.8g/kg/day was associated with a higher
      percentage of fat free mass among older adults. These results suggest meeting the
      protein recommendations of at least 0.8 g/kg/day may help to promote lower
      overall body mass, primarily through loss of fat mass rather than lean mass.

PMID- 27709228
TI  - Mini Nutritional Assessment Short-Form: Validation in Five Latin American Cities.
      SABE Study.
AB  - OBJECTIVES: To validate the short-form of the MNA (MNA-SF) and the cut-off point
      of 31 cm for calf circumference (CC) in older people in Latin America. METHODS: A
      cross-sectional study was conducted with 5,722 community-dwelling older subjects
      (range: 60-102 years) in Latin America's five main cities: Sao Paulo (Brazil),
      Santiago (Chile), Havana (Cuba), Mexico DF (Mexico) and Montevideo (Uruguay). All
      participants underwent an interview, which included anthropometric measurements,
      completing the MNA and obtaining socio-demographic, nutrition and health
      information. The short-form of the MNA consists of only six questions from the
      original 18. It has two versions: one using body mass index (BMI) and the second
      using CC as a surrogate. Cohen's Kappa was calculated to assess the agreement
      between the MNA and the MNA-SF; diagnostic tests were performed, and Receiver
      operating characteristic (ROC) curves were developed. Criterion-related validity
      was assessed in the Chilean sample. RESULTS: Both version of the MNA-SF showed
      high sensitivity and specificity with the MNA, showing good accuracy (0.88),
      although higher values were estimated for malnutrition and risk of malnutrition
      in the total sample by sex. The cut-off point of 31 cm for CC showed high
      sensitivity (74.6-94.4%), specificity (72.6-100%) and good area under the ROC
      curve (0.87-0.95) when compared with BMI. There was good agreement between MNA
      and both version of MNA-SF for identifying persons with malnutrition or a risk of
      malnutrition in the five cities (Kappa coefficient: 0.6193-0.7852). CONCLUSION:
      Both versions of the MNA-SF are population-screening tools of easy and fast
      application, with good accuracy for assessing malnutrition and risk of
      malnutrition in Latin American older people.

PMID- 27709229
TI  - Prevalence of and Risk Factors for Dysphagia in the Community Dwelling Elderly: A
      Systematic Review.
AB  - OBJECTIVES: This review clarifies current information regarding the prevalence of
      and risk factors associated with dysphagia (swallowing disorders) in the
      community dwelling elderly (CDE). A better understanding of prevalence and
      characteristics of dysphagia in the CDE will help to determine the scope of this
      problem. Understanding the scope of dysphagia is a critical first step towards
      early identification, management, and prevention of dysphagia related morbidities
      in the CDE. METHODS: Studies identified from multiple electronic databases
      (MEDLINE (Pubmed), PsychInfo, Google Scholar, EBSCO, PROQUEST, Web of Science and
      WorldCat dissertations and theses) evaluating prevalence and risk factors for
      dysphagia in the CDE were reviewed. Data from all eligible studies were
      abstracted by the first author and independently reviewed by two raters, using
      the Newcastle-Ottawa scale (NOS). RESULTS: 15 studies (n = 9947 participants)
      were eligible for inclusion. Studies included were all observational: 14 cross
      sectional and 1 prospective cohort. Significant heterogeneity was observed in
      methodology among studies of dysphagia in the CDE. The average NOS study quality
      rating was 4.54 points (SD: 0.9), with a mode of 4 points (range 3-6). Only 6 of
      the 15 studies were identified as high quality research studies, with a mean of
      5.33 points (SD: 0.47). Among reviewed studies, the prevalence of swallowing
      difficulty in the CDE ranged from 5% to 72%. However, the average prevalence of
      dysphagia estimated from the 6 high quality studies was 15%. Reported risk
      factors associated with dysphagia include advancing age; history of clinical
      disease; and physical frailty, including reduced ability to carry out activities
      of daily living. CONCLUSION: Research on dysphagia in CDE is modest and consists
      mostly of observational studies with diverse methodology. However, prevalence
      rate of 15% from the high quality research suggests a significant public health
      impact of this impairment. Identification of specific risk factors that cause
      dysphagia in the CDE is premature, given the rigor of published studies. Future
      research efforts should focus on developing a valid definition and assessment of
      dysphagia in this population before clarifying causative risk factors.

PMID- 27709230
TI  - Metabolic Syndrome Is not an Independent Risk Factor for Hearing Impairment.
AB  - OBJECTIVE: We aimed to investigate the association between metabolic syndrome
      (MS) and hearing impairment (HI) using nationally representative data from Korean
      adults. DESIGN, SETTING AND PARTICIPANTS: A total of 16,799 subjects (>=19 years
      old; 7,170 men and 9,629 women) who underwent pure tone audiometry testing were
      included in the analysis. Data were obtained from the fifth Korea National Health
      and Nutrition Examination Survey (2010-2012). Subjects were divided into two
      groups according to the presence of MS. RESULTS: Among the subjects with MS, 47%
      had HI. Logistic regression analysis revealed that MS was not an independent risk
      factor for HI, although increased fasting plasma glucose (OR 1.4, 95% CI: 1.1
      1.8) was independently associated with HI. In addition, older age, male sex, very
      low body mass index (<=17.5 kg/m2), lower education level, smoking history, and
      occupational noise exposure were independently associated with HI. For low
      frequency HI, independent risk factors included older age, lower educational
      level, lower economic status, and very low BMI (<=17.5 kg/m2). For high-frequency
      HI, independent risk factors included older age, male sex, lower educational
      level, lower economic status, increased blood pressure, lower high-density
      lipoprotein cholesterol, and smoking history. CONCLUSIONS: MS itself was not an
      independent risk factor for HI, and, among the individual metabolic components,
      only increased fasting plasma glucose was independently associated with HI.

PMID- 27709231
TI  - Novel Therapy of Hyperhomocysteinemia in Mild Cognitive Impairment, Alzheimer's
      Disease, and Other Dementing Disorders.
AB  - OBJECTIVES: Studies have produced conflicting results assessing
      hyperhomocysteinemia (HYH) treatment with B vitamins in patients with normal
      cognition, Alzheimer's disease and related disorders (ADRD). This study examined
      the effect of HYH management with L-methylfolate (LMF), methylcobalamin (MeCbl;
      B12), and N-acetyl-cysteine (CFLN: Cerefolin(r)/Cerefolin-NAC(r)) on cognitive
      decline. DESIGN: Prospective, case-control study of subjects followed
      longitudinally. SETTING: Outpatient clinic for cognitive disorders. PARTICIPANTS:
      116 ADRD patients (34 with HYH, 82 with No-HYH) met inclusion and exclusion
      criteria to participate. No study participant took B vitamins. INTERVENTION: HYH
      patients received CFLN, and No-HYH patients did not. MEASUREMENTS: Cognitive
      outcome measures included MCI Screen (memory), CERAD Drawings (constructional
      praxis), Ishihara Number Naming (object recognition), Trails A and B (executive
      function), and F-A-S test (verbal fluency). Dependent or predictor measures
      included demographics, functional severity, CFLN and no CFLN treatment duration,
      ADRD diagnosis, memantine and cholinesterase inhibitor treatment. Linear mixed
      effects models with covariate adjustment were used to evaluate rate of change on
      cognitive outcomes. RESULTS: The duration of CFLN treatment, compared to an
      equivalent duration without CFLN treatment, significantly slowed decline in
      learning and memory, constructional praxis, and visual-spatial executive function
      (Trails B). CFLN treatment slowed cognitive decline significantly more for
      patients with milder baseline severity. CFLN treatment effect increased as
      baseline functional severity decreased. The analytical model showed that
      treatment duration must exceed some minimum period of at least one year to slow
      the rate of cognitive decline. CONCLUSION: After covariate adjustment, HYH+CFLN
      significantly slowed cognitive decline compared to No-HYH+No-CFLN. Longer CFLN
      treatment duration, milder baseline severity, and magnitude of homocysteine
      reduction from baseline were all significant predictors. There are a number of
      factors that could account for disagreement with other clinical trials of B
      vitamin treatment of HYH. Moreover, CFLN is chemically distinct from commonly
      used B vitamins as both LMF and MeCbl are the fully reduced and bioactive
      functional forms; CLFN also contains the glutathione precursor, N-acetyl
      cysteine. The findings of other B vitamin trials of HYH can, therefore, only
      partly account for treatment effects of CFLN. These findings warrant further
      evaluation with a randomized, placebo-controlled trial.

PMID- 27709232
TI  - A Study on Neuroprotective Effects of Curcumin on the Diabetic Rat Brain.
AB  - The present study was aimed to study the neuroprotective therapeutic effect of
      curcumin on the male albino rat brain. Subarachnoid hemorrhage leads to severe
      mortality rate and morbidity, and oxidative stress is a crucial factor in
      subarachnoid hemorrhage. Therefore, we investigated the effect of curcumin on
      oxidative stress and glutamate and glutamate transporter-1 on a subarachnoid
      hemorrhage-induced male albino rats. The curcumin commonly used for the treatment
      and saline used for the control. Curcumin (10 mg/kg bwt) dissolved in saline and
      administered orally to the rats for one week. Glutamate, glutamate transporter-1,
      malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione
      reductase and lactate dehydrogenase (LDH) activities were determined. Glutamate
      level was lower in the curcumin-treated rats compared to their respective
      controls. Glutamate transporter-1 did not alter in the curcumin-treated rats
      compared to their controls. Glutamate transporter-1 protein expression is
      significantly reduced in the curcumin-treated rats. MDA levels decreased 18 and
      29 % in the hippocampus and the cortex region respectively. SOD (17% and 32%),
      and catalase (19% and 24%) activities were increased in the curcumin-treated
      hippocampus and the cortex region respectively. Glutathione reductase (13% and
      19%) and LDH (21% and 30%) activities were increased in the treated hippocampus
      and the cortex region respectively. The mRNA expression of NK-kB and TLR4 was
      significantly reduced following curcumin treatment. Taking all these data
      together, the curcumin found to be effective against oxidative stress and
      glutamate neurotoxicity in the male albino rats.

PMID- 27709233
TI  - Vitamin C Supplementation, APOE4 Genotype and Cognitive Functioning in a Rural
      Dwelling Cohort.
AB  - OBJECTIVE: Apolipoprotein E4 (APOE4) genotype has been implicated as a moderating
      factor in cognitive function studies. Although prior studies have suggested that
      vitamin C is associated with better cognitive function in elders, link between
      the two has been mixed. Limited data exist as to whether the APOE4 genotype
      influences these associations. Therefore, this study sought to determine whether
      the association between vitamin C and cognition in a rural community dwelling
      cohort differs by the APOE4 genotype. DESIGN AND PARTICIPANTS: Data were analyzed
      on 582 participants (n=183 men; n=399 women) from a rural community-based cohort.
      Cognition was assessed using the Repeatable Battery for the Assessment of
      Neuropsychological Status and The Executive Interview. APOE genotyping was
      ascertained by standard methods. The relation between vitamin C supplementation
      and cognition were analyzed first with ANOVA and then ANCOVA with age, gender,
      education as covariates. Analyses were initially run in the full sample and then
      split by APOE4 presence (yes/no). RESULTS: Overall, Vitamin C supplementation was
      associated with significantly better immediate memory (p=0.04), visuospatial
      skills (p=0.002), language (p=0.01), and global cognitive functioning (p=0.006).
      Among APOE4 non-carriers, vitamin C supplementation was positively associated
      with immediate memory (F[1,392] =6.7, p=0.01), visuospatial skills
      (F[1,391]=10.6, p=0.001), language (F[1,392]=13.0, p<0.001), attention
      (F[1,386]=7.9, p=0.005, and global cognition (F[1,382]=11.0, p=0.001. However,
      there was no significant link between vitamin C supplementation and cognition
      among APOE4 carriers. CONCLUSION: Vitamin C supplementation was found to be
      positively associated with cognition among this rural-dwelling community-based
      sample; however, the associations appeared to differ by APOE4 status. These data
      may suggest that targeted genotype-specific cognitive enhancement studies are
      needed to clarify the potential benefits of vitamin C supplementation.

PMID- 27709234
TI  - Early Nutritional Follow-Up after Discharge Prevents Deterioration of ADL
      Functions in Malnourished, Independent, Geriatric Patients Who Live Alone - A
      Randomized Clinical Trial.
AB  - OBJECTIVES: To compare the effects of two nutritional follow-up interventions
      with regard to preventing short-term deterioration in ADL, and to compare their
      effects on physical function, emotional health, and health-related quality of
      life. DESIGN: Randomized clinical trial with two intervention groups and one
      control group, and a follow-up period of eight weeks. SETTING: Intervention in
      the participants' homes after discharge from hospital. PARTICIPANTS: Inclusion:
      Malnourished geriatric patients and patients at risk of malnutrition (MNA<24),
      aged 75 years and older, living at home and alone. Exclusion: Nursing home
      residents and patients with terminal illnesses or cognitive impairment.
      Randomization: At discharge, the patients were assigned to one of three groups:
      'home visit', 'telephone consultation', or 'control' group. INTERVENTION:
      Individually tailored nutritional counselling of the patient and the patient's
      daily home carer by a clinical dietician one, two, and four weeks after discharge
      from hospital. The counselling was either in-person at the patients' homes, or by
      telephone. The control group received no follow-up after discharge. MEASUREMENTS:
      Primary outcome: Change in ADL (Barthel-100 score) at discharge and eight weeks
      later. SECONDARY OUTCOMES: Change in physical performance (handgrip strength, 30
      sec. chair stand test, CAS), quality of life and depression measurements (SF-36,
      Depression List, Geriatric Depression Score), and Avlund mobility-tiredness score
      (Mob-T). RESULTS: Two-hundred and eight participants were randomized, 73 to home
      visits and 68 to telephone consultations. The control group comprised 67
      patients. The mean age of the participants was 86.1 years. At eight weeks after
      discharge, 157 completed the follow-up (home visit 52, telephone consultation 51,
      and control group 54). The mean age of these patients was 85.8 years. More
      patients in the home visit group improved or maintained their ADL (96%), compared
      to the telephone (75%) and control groups (72%), p<0.01. No difference was
      detected among the groups with regard to physical measurements, health-related
      quality of life, and emotional health. CONCLUSION: Early nutritional follow-up
      after discharge, performed as home visits, prevents deterioration of ADL in
      malnourished, independent, geriatric patients who live alone and thereby
      preserves their independence.

PMID- 27709235
TI  - Frailty, Diabetes, and Mortality in Middle-Aged African Americans.
AB  - BACKGROUND: Older adult frail diabetics have high mortality risk, but data are
      limited regarding frail late middle-aged diabetics, especially for African
      Americans. The aim of this study is to examine the association of diabetes with
      health outcomes and frailty in the African American Health (AAH) study. METHODS:
      AAH is a population-based longitudinal cohort study. Participants were African
      Americans (N=998) ages 49 to 65 years at baseline. Cross-sectional comparisons
      for diabetes included disability, function, physical performance, cytokines, and
      frailty. Frailty measures included the International Academy of Nutrition and
      Aging [FRAIL] frailty scale, Study of Osteoporotic Fractures [SOF] frailty scale,
      Cardiovascular Health Study [CHS] frailty scale, and Frailty Index [FI]).
      Longitudinal associations for diabetes included new ADLs >= 1 and mortality at 9
      year follow-up. RESULTS: Diabetics were more likely to be frail using any of the
      4 frailty scales than were non-diabetics. Frail diabetics, compared to nonfrail
      diabetics, reported significantly increased falls in last 1 year, higher IADLs
      and higher LBFLs. They demonstrated worse performance on the SPPB, one-leg stand,
      and grip strength; and higher Tumor Necrosis Factor receptors (sTNFR1 and
      sTNFR2). Mortality and 1 or more new ADLs also were increased among frail
      compared to nonfrail diabetics when followed for 9 years. CONCLUSIONS: Frailty in
      middle-aged African American persons with diabetes is associated with having more
      disability and functional limitations, worse physical performance, and higher
      cytokines (sTNFR1 and sTNFR2 only). Middle-aged African Americans with diabetes
      have an increased risk of mortality and frail diabetics have an even higher risk
      of death, compared to nonfrail diabetics.

PMID- 27709236
TI  - Pre-Frailty, Frailty, and Multimorbidity: Prevalences and Associated
      Characteristics from Two French National Surveys.
AB  - OBJECTIVE: To estimate the prevalence of pre-frailty, frailty and multimorbidity
      in individuals without disability in France. To describe independent determinants
      of each indicators. DESIGN: Two nationally representative cross-sectional French
      surveys. SETTINGS: Wave 2012 of the Health, Health Care and Insurance Survey
      (Enquete Sante et Protection Sociale, ESPS) and data from the Disability
      Healthcare Household section Survey (Enquete Handicap Sante - Menages, HSM) from
      2008. PARTICIPANTS: Two representative samples of the French population aged 55
      and older (n=4,328 and n=12,295). MEASUREMENTS: Frailty was assessed using
      Fried's frailty phenotype and multimorbidity was defined as having had at least
      two groups of the following groups of comorbidities in the last 12 months (cardio
      or cerebrovascular disease, diabetes, chronic respiratory disease, arthralgia,
      depression). Independent determinants were studied using weighted logistic
      regressions. RESULTS: In the French population over 55 and free of disability, 55
      to 62% of individuals were either frail, pre-frail or multimorbid, 22 to 25%
      being frail or multimorbid. ESPS and HSM prevalences for frailty (11.1% [9.3%
      12.1%] and 12.3% [11.5%-13.0%]) and multimorbidity (14.9% [13.6%-16.2%] and 16.8%
      [15.9%-17.7%]) were consistent across studies. Both frailty and multimorbidity
      prevalences were associated with age. On the other hand, pre-frailty prevalence
      varied consistently between studies (from 38 to 48%) and was not significantly
      associated with age. We found that more than 60% of frail subjects did not
      present with multimorbidity and around 70% of subjects with multimorbidity were
      not frail. Determinants of pre-frailty and multimorbidity but not frailty
      depended on sex. Similar factors were associated with frailty and multimorbidity
      in women (older age, functional decline, poor mental health, financial
      difficulties) while only poor mental health was independently associated with
      both indicators in men. CONCLUSION: Our study highlights that in France, among
      individuals older than 55 years-old and free of disability, around 25% are either
      frail or multimorbid; another 30% to 40% being pre-frail. Pre-frailty, frailty
      and multimorbidity are known to be associated with adverse health outcomes and
      important economic costs. The health system must adapt to respond to the needs of
      its aging population. In addition, given the efficient impact of prevention
      actions, our findings emphasize the need to implement prevention strategies
      against Frailty and multimorbidity in France.

PMID- 27709237
TI  - Visual Impairment Screening at the Geriatric Frailty Clinic for Assessment of
      Frailty and Prevention of Disability at the Gerontopole.
AB  - OBJECTIVES: To evaluate visual performance and factors associated with abnormal
      vision in patients screened for frailty at the Geriatric Frailty Clinic (GFC) for
      Assessment of Frailty and Prevention of Disability at Toulouse University
      Hospital. DESIGN: Retrospective, observational cross-sectional, single-centre
      study. SETTING: Institutional practice. PARTICIPANTS: Patients were screened for
      frailty during a single-day hospital stay between October 2011 and October 2014
      (n = 1648). MEASUREMENTS: Collected medical records included sociodemographic
      data (including living environment and educational level), anthropometric data,
      and clinical data. The general evaluation included the patient's functional
      status using the Activities of Daily Living (ADL) scale and the Instrumental
      Activity of Daily Living (IADL) scale, the Mini-Mental State Examination (MMSE)
      for cognition testing, and the Short Physical Performance Battery (SPPB) for
      physical performance. We also examined Body Mass Index (BMI), the Mini
      Nutritional Assessment (MNA), and the Hearing Handicap Inventory for the Elderly
      Screening (HHIE-S) tool. The ophthalmologic evaluation included assessing visual
      acuity using the Snellen decimal chart for distant vision, and the Parinaud chart
      for near vision. Patients were divided into groups based on normal distant/near
      vision (NDV and NNV groups) and abnormal distant/near vision (ADV and ANV
      groups). Abnormal distant or near vision was defined as visual acuity inferior to
      20/40 or superior to a Parinaud score of 2, in at least one eye. Associations
      with frailty-associated factors were evaluated in both groups. RESULTS: The mean
      age of the population was 82.6 +/- 6.2 years. The gender distribution was 1,061
      females (64.4%) and 587 males (35.6%). According to the Fried criteria, 619
      patients (41.1%) were pre-frail and 771 (51.1%) were frail. Distant and near
      vision data were available for 1425 and 1426 patients, respectively. Distant
      vision was abnormal for 437 patients (30.7%). Near vision was abnormal for 199
      patients (14%). Multiple regression analysis showed that abnormal distant vision
      as well as abnormal near vision were independently associated with greater age (P
      < 0.01), lower educational level (P < 0.05), lower performance on the MMSE (P <
      0.001), and lower autonomy (P < 0.02), after controlling for age, gender,
      educational level, Fried criteria, and MMSE score. CONCLUSION: The high
      prevalence of visual disorders observed in the study population and their
      association with lower autonomy and cognitive impairment emphasises the need for
      systematic screening of visual impairments in the elderly. Frailty was not found
      to be independently associated with abnormal vision.

PMID- 27709240
TI  - Ionic liquids and cyclodextrin inclusion complexes: limitation of the affinity
      capillary electrophoresis technique.
AB  - The state of the art of inclusion complex formation between cyclodextrins and
      ionic liquids is reported. Mechanisms, stoichiometries, and binding constants are
      summarized and classified by anion. We investigated the supramolecular
      interactions between the beta-cyclodextrin cavity and six ionic liquids based on
      1-dodecyl-3-methylimidazolium by affinity capillary electrophoresis and compared
      the results with those obtained by isothermal titration calorimetry. We show that
      the presence of basic or acidic buffers leads to a metathesis reaction,
      underlining the limitation of the affinity capillary electrophoresis technique.

PMID- 27709239
TI  - Patient-specific instruments for total knee arthroplasty can accurately predict
      the component size as used peroperative.
AB  - PURPOSE: Patients-specific instruments (PSI) for implantation of total knee
      arthroplasty (TKA) can be used to predict the implant size for both the femur and
      the tibia component. This study aims to determine the impact of approval of the
      PSI planning for TKA on the frequency of, and reason for intraoperative changes
      of implant sizes. METHODS: The clinical records of 293 patients operated with MRI
      (90.4 %) and CT-based (9.6 %) PSI were reviewed for actual used implant size.
      Preoperative default planning from the technician and approved planning by the
      operating surgeon were compared with the intraoperative implanted component size
      for both the femur and tibia. Intraoperative reason for not following the default
      sizes was outdated. Furthermore, MRI- and CT-based PSI were compared for these
      outcomes. RESULTS: In 93.9 and 91.1 % for, respectively, the femur and tibia
      (n.s.), the surgeon planned size was implanted during surgery. The predicted size
      of the femur (p < 0.00) and the tibia (p < 0.00) component planned by a
      technician differed from the implanted component sizes in 62 (21.2 %) and 51
      (17.4 %) patients, respectively. In 17 cases, the femoral component size was
      adapted intraoperative based on the expert opinion of the operating surgeon. In
      26 cases, the tibia component was changed during the surgery because of a
      mediolateral overhang, sclerotic bone, medial or lateral release, limited
      extension and/or fixed varus deformity. The results between the MRI- and CT-based
      PSI did not differ (n.s.). CONCLUSIONS: PSI is a tool to help the surgeon to
      achieve the best possible results during TKA. The planning made by a technician
      should always be validated and approved by the operating surgeon who has the
      ultimate responsibility regarding the operation. With PSI, the operating surgeon
      is able to minimize intraoperative implant size errors in advance to improve
      operating room efficiency with possible lowering hospital costs per procedure.
      LEVELS OF EVIDENCE: III.

PMID- 27709238
TI  - Body Composition and Anti-Neoplastic Treatment in Adult and Older Subjects - A
      Systematic Review.
AB  - BACKGROUND: The estimation of the risk of poor tolerance and overdose of
      antineoplastic agents protocols represents a major challenge in oncology,
      particularly in older patients. We hypothesize that age-related modifications of
      body composition (i.e. increased fat mass and decreased lean mass) may
      significantly affect tolerance to chemotherapy. METHOD: We conducted a systematic
      review for the last 25 years (between 1990 and 2015), using US National library
      of Medicine Medline electronic bibliographic database and Embase database of
      cohorts or clinical trials exploring (i) the interactions of body composition
      (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or
      Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to
      chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies
      on body composition. RESULTS: Our search identified 1504 articles. After a
      selection (using pre-established criteria) on titles and abstract, 24 original
      articles were selected with 3 domains of interest: impact of body composition on
      pharmacokinetics (7 articles), relationship between body composition and
      chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body
      composition (11 articles). The selected studies suggested that pharmacokinetic
      was influenced by lean mass, that lower lean mass could be correlated with
      toxicity, and that sarcopenic patients experienced more toxicities that non
      sarcopenic patients. Regarding fat mass, results were less conclusive. No studies
      specifically explored the topic of body composition in older cancer patients.
      CONCLUSIONS: Plausible pathophysiological pathways linking body composition,
      toxicity, and pharmacokinetics are sustained by the actual review. However,
      despite the growing number of older cancer patients, our review highlighted the
      lack of specific studies in the field of anti-neoplastic agents toxicity
      regarding body composition conducted in elderly.

PMID- 27709241
TI  - [Ambulatory care of patients with somatically unexplained complaints : A
      comparative qualitative study].
AB  - BACKGROUND: The aim of this study was to compare the approach of general
      practitioners (GP) and outpatient specialists for psychiatry, neurology or
      psychosomatic medicine to patients with somatically unexplained complaints.
      METHODS: Qualitative interviews were conducted with general practitioners in
      Berlin and with outpatient specialists. Interviews were analyzed by qualitative
      content analysis. RESULTS: Both GPs and specialists rarely used structured
      diagnostic instruments. Guidelines are seen and used with reservation throughout
      the different specialties. Similar to the GPs, most of the specialists surveyed
      in this study had reservations against the necessity of a precise coding
      according to the International Classification of Diseases (ICD). CONCLUSION: In
      outpatient care the concern for the individual patient is the connecting element
      between different medical specialties. This results in a differential diagnostic
      and therapeutic approach that is not automatically in line with guidelines. The
      development of common concepts in ambulatory care might help to meet the demands
      of this complex group of patients with somatically unexplained complaints.

PMID- 27709242
TI  - [Care differences in a consultation and liaison service].
AB  - BACKGROUND: The investigation of the real density of care by a consultation
      liaison service (CLS) as a function of patient groups, settings and diagnoses
      makes sense with respect to a better allocation of resources. OBJECTIVE: Are
      there differences concerning the density of care by a CLS in a general hospital
      depending on patient groups and on the psychiatric diagnosis? METHOD: A
      retrospective (2012-2015) survey of all consultations (n = 7081 corresponding to
      4080 patients) was carried out based on the CLS documentation for quality
      assurance. Bivariate tests (i.e. chi2-test and ANOVA) and multivariate linear and
      logistic models were used to investigate group differences and associations.
      RESULTS: The number of consultations achieved corresponded to 3.2 % of the total
      admissions to hospital, especially internal medicine (22.3 %), surgery (26.1 %)
      as well as gynecology and obstetrics (21.1 %). A suicide attempt was the reason
      for treatment in 3.3 %. Each patient received on average 1.7 consultations
      lasting 75 min but only 25 % received 2 or more consultations. Patients with
      psychiatric comorbidities, non-oncology patients as well as female and young
      patients received a more intensive care by CLS. Patients with depressive and
      somatoform disorders received a higher density of treatment. DISCUSSION: The
      psychotherapeutic interventions performed did not follow the expected diagnostic
      patterns in other settings. Systemic interventions with indirect treatment should
      be given priority in older patients and especially in patients with organic
      mental disorders.

PMID- 27709243
TI  - [Anatomy and biomechanics of the scaphoid].
AB  - The scaphoid is biomechanically and clinically of great importance for function
      of the wrist. In the literature, its anatomy and biomechanics are clearly
      underrepresented as well as underestimated. In the following review the scaphoid
      will be presented in more detail, according to recent information and findings.
      Not only will the origin of the name and the history of previous names, such as
      cotyloid or navicular, be introduced, but also for the first time in medical
      literature the significant phylogeny and ontogeny of the scaphoid will be shown.
      Moreover, the clinically very important blood supply, the ligaments of the
      scaphoid and relevant biomechanical details will be described.

PMID- 27709244
TI  - [Prevention of aortic erosion by a bone cement skid : Thoracic endovascular
      aortic repair following kyphoplasty].
AB  - The underlying case report describes the successful endovascular prevention of an
      aortic injury by a bone cement skid after kyphoplasty. The intervention was
      performed in order to prohibit fatal aortic rupture or embolisation and
      underlines the role of vascular surgery techniques in interdisciplinary clinical
      networks.

PMID- 27709245
TI  - Cystic fibrosis: a clinical view.
AB  - Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on
      chromosome 7, is complex and greatly variable in clinical expression. Airways,
      pancreas, male genital system, intestine, liver, bone, and kidney are involved.
      The lack of CFTR or its impaired function causes fat malabsorption and chronic
      pulmonary infections leading to bronchiectasis and progressive lung damage.
      Previously considered lethal in infancy and childhood, CF has now attained median
      survivals of 50 years of age, mainly thanks to the early diagnosis through
      neonatal screening, recognition of mild forms, and an aggressive therapeutic
      attitude. Classical treatment includes pancreatic enzyme replacement, respiratory
      physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant
      proportion of patients with severe symptoms still requires lung or, less
      frequently, liver transplantation. The great number of mutations and their
      diverse effects on the CFTR protein account only partially for CF clinical
      variability, and modifier genes have a role in modulating the clinical expression
      of the disease. Despite the increasing understanding of CFTR functioning, several
      aspects of CF need still to be clarified, e.g., the worse outcome in females, the
      risk of malignancies, the pathophysiology, and best treatment of comorbidities,
      such as CF-related diabetes or CF-related bone disorder. Research is focusing on
      new drugs restoring CFTR function, some already available and with good clinical
      impact, others showing promising preliminary results that need to be confirmed in
      phase III clinical trials.

PMID- 27709246
TI  - Functional Metagenomics as a Tool for Identification of New Antibiotic Resistance
      Genes from Natural Environments.
AB  - Antibiotic resistance has become a major concern for human and animal health, as
      therapeutic alternatives to treat multidrug-resistant microorganisms are rapidly
      dwindling. The problem is compounded by low investment in antibiotic research and
      lack of new effective antimicrobial drugs on the market. Exploring environmental
      antibiotic resistance genes (ARGs) will help us to better understand bacterial
      resistance mechanisms, which may be the key to identifying new drug targets.
      Because most environment-associated microorganisms are not yet cultivable,
      culture-independent techniques are essential to determine which organisms are
      present in a given environmental sample and allow the assessment and utilization
      of the genetic wealth they represent. Metagenomics represents a powerful tool to
      achieve these goals using sequence-based and functional-based approaches.
      Functional metagenomic approaches are particularly well suited to the
      identification new ARGs from natural environments because, unlike sequence-based
      approaches, they do not require previous knowledge of these genes. This review
      discusses functional metagenomics-based ARG research and describes new
      possibilities for surveying the resistome in environmental samples.

PMID- 27709248
TI  - Two injection digital block versus single subcutaneous palmar injection block for
      finger lacerations.
AB  - PURPOSE: We aimed to compare two digital nerve block techniques in patients due
      to traumatic digital lacerations. METHODS: This was a randomized-controlled study
      designed prospectively in the emergency department of a university-based training
      and research hospital. Randomization was achieved by sealed envelopes. Half of
      the patients were randomised to traditional (two-injection) digital nerve block
      technique while single-injection digital nerve block technique was applied to the
      other half. Score of pain due to anesthetic infiltration and suturing, onset time
      of total anesthesia, need for an additional rescue injection were the parameters
      evaluated with both groups. Epinephrin added lidocaine hydrochloride preparation
      was used for the anesthetic application. Visual analog scale was used for the
      evaluation of pain scores. Outcomes were compared by using Mann-Whitney U test
      and Student t-test. RESULTS: Fifty emergency department patients >=18 years
      requiring digital nerve block were enrolled in the study. Mean age of the
      patients was 33 (min-max: 19-86) and 39 (78 %) were male. No statistically
      significant difference was found between the two groups in terms of our main
      parameters; anesthesia pain score, suturing pain score, onset time of total
      anesthesia and rescue injection need. CONCLUSION: Single injection volar digital
      nerve block technique is a suitable alternative for digital anesthesias in
      emergency departments.

PMID- 27709249
TI  - Cocaine-like discriminative stimulus effects of amphetamine, cathinone,
      methamphetamine, and their 3,4-methylenedioxy analogs in male rhesus monkeys.
AB  - RATIONALE: Synthetic cathinones have emerged as the newest class of abused
      monoamine transporter substrates. Structurally, these compounds are all beta
      ketone amphetamine (cathinone) analogs. Whether synthetic cathinone analogs
      produce differential behavioral effects from their amphetamine analog
      counterparts has not been systematically examined. Preclinical drug
      discrimination procedures have been useful for determining the structure activity
      relationships (SARs) of abused drugs; however, direct comparisons between
      amphetamine and cathinone analogs are lacking and, in particular, in non-human
      primate models. OBJECTIVES: The study aim was to determine the potency and time
      course of (+/-)-amphetamine, (+/-)-cathinone, and (+/-)-methamphetamine and their
      3,4-methylenedioxy analogs (+/-)-MDA, (+/-)-MDC, and (+/-)-MDMA, respectively, to
      produce cocaine-like discriminative stimulus effects. If cathinone analogs have
      similar behavioral pharmacological properties to their amphetamine counterparts,
      then we would predict similar potencies and efficacies to produce cocaine-like
      discriminative stimulus effects. METHODS: Male rhesus monkeys (n = 4) were
      trained to discriminate intramuscular cocaine (0.32 mg/kg) from saline in a two
      key food-reinforced discrimination procedure. RESULTS: Racemic amphetamine,
      cathinone, and methamphetamine produced dose-dependent and full substitution,
      >=90 % cocaine-appropriate responding, in all monkeys. Addition of 3,4
      methylenedioxy moiety attenuated both the potency and efficacy of amphetamine
      (MDA), cathinone (MDC), and methamphetamine (MDMA) to produce full cocaine-like
      effects. Moreover, the cocaine-like effects of amphetamine and cathinone were
      attenuated to a greater extent than those of methamphetamine or previously
      published methcathinone (Smith et al. 2016). CONCLUSION: The presence of an N
      methyl group blunted both the potency and the efficacy shift of the 3,4
      methylenedioxy addition for both amphetamine and cathinone analogs.

PMID- 27709250
TI  - Obituary: Tomoji Yanagita, M.D., Ph.D. (1930-2016)-psychopharmacologist
      extraordinaire.

PMID- 27709247
TI  - Spatiotemporal Characterization of San Francisco Bay Denitrifying Communities: a
      Comparison of nirK and nirS Diversity and Abundance.
AB  - Denitrifying bacteria play a critical role in the estuarine nitrogen cycle.
      Through the transformation of nitrate into nitrogen gas, these organisms
      contribute to the loss of bioavailable (i.e., fixed) nitrogen from low-oxygen
      environments such as estuary sediments. Denitrifiers have been shown to vary in
      abundance and diversity across the spatial environmental gradients that
      characterize estuaries, such as salinity and nitrogen availability; however,
      little is known about how their communities change in response to temporal
      changes in those environmental properties. Here, we present a 1-year survey of
      sediment denitrifier communities along the estuarine salinity gradient of San
      Francisco Bay. We used quantitative PCR and sequencing of functional genes coding
      for a key denitrifying enzyme, dissimilatory nitrite reductase, to compare two
      groups of denitrifiers: those with nirK (encoding copper-dependent nitrite
      reductase) and those with nirS (encoding the cytochrome-cd 1-dependent variant).
      We found that nirS was consistently more abundant and more diverse than nirK in
      all parts of the estuary. The abundances of the two genes were tightly linked
      across space but differed temporally, with nirK peaking when temperature was low
      and nirS peaking when nitrate was high. Likewise, the diversity and composition
      of nirK- versus nirS-type communities differed in their responses to seasonal
      variations, though both were strongly determined by site. Furthermore, our
      sequence libraries detected deeply branching clades with no cultured isolates,
      evidence of enormous diversity within the denitrifiers that remains to be
      explored.

PMID- 27709251
TI  - Low validation rate of quantitative trait loci for Gibberella ear rot resistance
      in European maize.
AB  - KEY MESSAGE: Six quantitative trait loci (QTL) for Gibberella ear rot resistance
      in maize were tested in two different genetic backgrounds; three QTL displayed an
      effect in few near isogenic line pairs. Few quantitative trait loci (QTL) mapping
      studies for Gibberella ear rot (GER) have been conducted, but no QTL have been
      verified so far. QTL validation is prudent before their implementation into
      marker-assisted selection (MAS) programs. Our objectives were to (1) validate six
      QTL for GER resistance, (2) evaluate the QTL across two genetic backgrounds, (3)
      investigate the genetic background outside the targeted introgressions. Pairs of
      near isogenic lines (NILs) segregating for a single QTL (Qger1, Qger2, Qger10,
      Qger13, Qger16, or Qger21) were developed by recurrent backcross until generation
      BC3S2. Donor parents (DP) carrying QTL were backcrossed to a susceptible (UH009)
      and a moderately resistant (UH007) recurrent parent. MAS was performed using five
      SNP markers covering a region of 40 cM around each QTL. All NILs were genotyped
      with the MaizeSNP50 assay and phenotyped for GER severity and deoxynivalenol and
      zearalenone content. Traits were significantly (P < 0.001) intercorrelated. Out
      of 34 NIL pairs with the UH009 genetic background, three pairs showed significant
      differences in at least one trait for three QTL (Qger1, Qger2, Qger13). Out of 25
      NIL pairs with the UH007 genetic background, five pairs showed significant
      differences in at least one trait for two QTL (Qger2, Qger21). However, Qger16,
      Qger10 and Qger13 were most likely false positives. The genetic background
      possibly affected NIL pairs comparisons due to linkage drag and/or epistasis with
      residual loci from the DP in non-target regions. In conclusion, validation rates
      were disappointingly low, which further indicates that GER resistance is
      controlled by many low-effect QTL.

PMID- 27709252
TI  - Host plant quantitative trait loci affect specific behavioral sequences in
      oviposition by a stem-mining insect.
AB  - KEY MESSAGE: Genetic diversity in quantitative loci associated with plant traits
      used by insects as cues for host selection can influence oviposition behavior and
      maternal choice. Host plant selection for oviposition is an important determinant
      of progeny performance and survival for phytophagous insects. Specific cues from
      the plant influence insect oviposition behavior; but, to date, no set of host
      plant quantitative trait loci (QTLs) have been shown to have an effect on
      behavioral sequences leading to oviposition. Three QTLs in wheat (Triticum
      aestivum L.) have been identified as influencing resistance to the wheat stem
      sawfly (WSS) (Cephus cinctus Norton). Wheat near-isogenic lines (NILs) for each
      of the three QTLs were used to test whether foraging WSS were able to
      discriminate variation in plant cues resulting from allelic changes. A QTL on
      chromosome 3B (Qss-msub-3BL) previously associated with stem solidness and larval
      antibiosis was shown to affect WSS oviposition behavior, host preference, and
      field infestation. Decreased preference for oviposition was also related to a QTL
      allele on chromosome 2D (Qwss.msub-2D). A QTL on chromosome 4A (Qwss.msub-4A.1)
      affected host plant attractiveness to foraging females, but did not change
      oviposition preference after females landed on the stem. These findings show that
      oviposition decisions regarding potential plant hosts require WSS females to
      discriminate signals from the plant associated with allelic variation at host
      plant quantitative loci. Allele types in a host plant QTL associated with
      differential survival of immature progeny can affect maternal choices for
      oviposition. The multidisciplinary approach used here may lead to the
      identification of plant genes with important community consequences, and may
      complement the use of antibiosis due to solid stems to control the wheat stem
      sawfly in agroecosystems.

PMID- 27709254
TI  - ?

PMID- 27709253
TI  - Statin use decreases coagulation in users of vitamin K antagonists.
AB  - PURPOSE: The purpose of the study is to determine the immediate and long-term
      effect of statins on coagulation in patients treated with vitamin K antagonists
      (VKAs). METHODS: We selected patients on VKAs of two Dutch anticoagulation
      clinics who initiated treatment with a statin between 2009 and 2013. Patients who
      initiated or stopped concomitant drugs that interact with VKAs or were
      hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin
      initiation was compared with the last VKA dosage before the statin was started.
      Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were
      calculated with a paired student t test. RESULTS: Four hundred thirty-five
      phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users
      (mean age 69 years, 58 % men) were included. After start of statin use, the
      immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At
      6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and
      0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before
      first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01
      to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11
      mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower. CONCLUSIONS: Initiation of
      statin treatment was associated with an immediate and long-term minor although
      statistically significant decrease in VKA dosage in both phenprocoumon and
      acenocoumarol users, which suggests that statins may have anticoagulant
      properties.

PMID- 27709257
TI  - A new frameshift mutation of the beta-spectrin gene associated with hereditary
      spherocytosis.

PMID- 27709258
TI  - The utility of diffusion-weighted imaging to assess acute renal parenchymal
      changes due to unilateral ureteral stone obstruction.
AB  - Our aim in this study was to evaluate the use of diffusion-weighted imaging (DWI)
      for acute renal parenchymal changes occurring as a result of unilateral ureteral
      obstruction due to stones. Twenty four patients with obstructed and opposite
      unobstructed kidney were enrolled in this prospective study. DWI was used at two
      different b values (b = 0 s/mm2 and b = 1000 s/mm2). Apparent diffusion
      coefficient (ADC) measurements were completed on the upper pole, central section
      and lower pole parenchyma of both kidneys. ADC values were calculated. The
      unpaired t test was used to assess differences between the groups. The results of
      measurements identified a reduction in ADC values in obstructed renal parenchyma
      compared to unobstructed opposite renal parenchyma. The reduction in ADC values
      was greater in the upper and lower pole parenchyma and was statistically
      significant (p < 0.001, for both). Diffusion changes in renal parenchyma due to
      acute unilateral ureteral obstruction linked to stone may be quantitatively shown
      with DWI. The reduction in ADC values was more pronounced in the upper and lower
      pole parenchyma.

PMID- 27709259
TI  - A "doughnut" in the abdomen.

PMID- 27709260
TI  - Solitary subcutaneous sarcoidosis with massive chronic prepatellar bursal
      involvement.
AB  - A 56-year-old man presented with a painless prepatellar mass of the left knee. MR
      images demonstrated a large, well-defined mass with heterogeneous intermediate
      signal intensity on T1- and proton density-weighted images. Mild, heterogeneous
      enhancement was noted after the intravenous administration of gadolinium.
      Diagnostic imaging included atypical soft-tissue infection, fibrogranulomatous
      reaction, gouty tophus, rheumatoid nodule and xanthoma or possibly malignancy.
      The histopathological examination revealed sarcoidosis involving the prepatellar
      bursa.

PMID- 27709261
TI  - [Non-selective primary prevention programs for childhood overweight : An
      overview].
AB  - BACKGROUND: Despite an obvious stabilization the prevalence of childhood
      overweight and obesity is still too high. Since childhood obesity may track into
      adulthood and lead to major health consequences, effective primary prevention
      programs are of high relevance. OBJECTIVE: In recent years several universal
      primary prevention programs, measures or projects have been developed and
      evaluated in Germany. This paper gives an overview. METHODS: An internet search
      and a search in the archive of the Deutsche Arzteblatt were conducted to identify
      universal programs in Germany from 2006 to 2015. We used the combination of
      primary prevention, children, obesity and project for this online search.
      RESULTS: We identified 38 programs and measures. After exclusion of non-adequate
      interventions (e. g. selective instead of universal) and any duplicates we
      selected 13 projects to be described. DISCUSSION: Some projects provided
      insufficient information since they have not been adequately published. On the
      positive side, most projects simultaneously addressed various potential risk
      factors and achieved a successful networking of various relevant actors. In
      addition, many projects strived for creating the groundwork to allow for a
      sustainable change in the living environment of children. However, despite the
      fact that the concept of most projects was theory-based in most cases only weak
      intervention effects were observed on strong endpoints like anthropometric
      indicators and on health-related behaviors.

PMID- 27709262
TI  - [Prevention of overweight and obesity in children and adolescents : Critical
      appraisal of the evidence base].
AB  - BACKGROUND: Despite careful planning and implementation, overweight/obesity
      prevention interventions in children and adolescents typically show no,
      inconsistent or merely weak effects. Such programs usually aim at behavior
      changes, rarely also at environmental changes, that draw upon conventional wisdom
      regarding the commonly accepted determinants of childhood overweight/obesity.
      OBJECTIVE: This paper evaluates the evidence base of the apparently overweight
      /obesity-related determinants diet, physical activity and stress. The results of
      international intervention studies are discussed against this background. METHODS
      AND MATERIALS: Based on the mediating-moderating variable model, we investigate
      the effect of theory specified mediating variables and how potential moderating
      variables may impact these relationships. RESULTS: Contrary to common beliefs,
      recent research has revealed inconsistent evidence regarding associations between
      potentially obesogenic behaviors and overweight/obesity in youth. Moreover, the
      evidence for strong and causal relationships between mediating variables and
      targeted behaviors seems to be inconsistent. In addition, inadequate attention is
      paid to moderating effects. DISCUSSION: The etiology of overweight/obesity in
      youth is likely the result of a complex interplay of multi-causal influences.
      Future prevention interventions would benefit from a more thorough understanding
      of the complex relationships that have been hypothesized and of the mechanisms of
      suspected behaviors for affecting overweight/obesity. Only if substantial change
      can be demonstrated in mediators with reasonable effort under real world
      circumstances, it will make sense to progress to community behavior change
      trials.

PMID- 27709264
TI  - Long-term physical morbidity in ARDS survivors.

PMID- 27709263
TI  - Refractory septic shock in children: a European Society of Paediatric and
      Neonatal Intensive Care definition.
AB  - PURPOSE: Although overall paediatric septic shock mortality is decreasing,
      refractory septic shock (RSS) is still associated with high mortality. A
      definition for RSS is urgently needed to facilitate earlier identification and
      treatment. We aim to establish a European society of paediatric and neonatal
      intensive care (ESPNIC) experts' definition of paediatric RSS. METHODS: We
      conducted a two-round Delphi study followed by an observational multicentre
      retrospective study. One hundred and fourteen paediatric intensivists answered a
      clinical case-based, two-round Delphi survey, identifying clinical items
      consistent with RSS. Multivariate analysis of these items in a development single
      centre cohort (70 patients, 30 % mortality) facilitated development of RSS
      definitions based on either a bedside or computed severity score. Both scores
      were subsequently tested in a validation cohort (six centres, 424 patients, 11.6
      % mortality). RESULTS: From the Delphi process, the draft definition included
      evidence of myocardial dysfunction and high blood lactate levels despite high
      vasopressor treatment. When assessed in the development population, each item was
      independently associated with the need for extracorporeal life support (ECLS) or
      death. Resultant bedside and computed septic shock scores had high discriminative
      power against the need for ECLS or death, with areas under the receiver operating
      characteristics curve of 0.920 (95 % CI 0.89-0.94), and 0.956 (95 % CI 0.93
      0.97), respectively. RSS defined by a bedside score equal to or higher than 2 and
      a computed score equal to or higher than 3.5 was associated with a significant
      increase in mortality. CONCLUSIONS: This ESPNIC definition of RSS accurately
      identifies children with the most severe form of septic shock.

PMID- 27709265
TI  - Increased incidence of co-infection in critically ill patients with influenza.
AB  - BACKGROUND: Co-infection is frequently seen in critically ill patients with
      influenza, although the exact rate is unknown. We determined the rate of co
      infection, the risk factors and the outcomes associated with co-infection in
      critically ill patients with influenza over a 7-year period in 148 Spanish
      intensive care units (ICUs). METHODS: This was a prospective, observational,
      multicentre study. Influenza was diagnosed using the polymerase chain reaction.
      Co-infection had to be confirmed using standard bacteriological tests. The
      primary endpoint of this analysis was the presence of community-acquired co
      infection, with secondary endpoints including ICU, 28-day and hospital mortality.
      RESULTS: Of 2901 ICU patients diagnosed with influenza, 482 (16.6 %) had a co
      infection. The proportion of cases of co-infection increased from 11.4 %
      (110/968) in 2009 to 23.4 % (80/342) in 2015 (P < 0.001). Compared with patients
      without co-infection, patients with co-infection were older [adjusted odds ratio
      (aOR) 1.1, 95 % confidence interval 1.1-1.2; P < 0.001] and were more frequently
      immunosuppressed due to existing HIV infection (aOR 2.6 [1.5-4.5]; P < 0.001) or
      preceding medication (aOR 1.4 [1.1-1.9]; P = 0.03). Co-infection was an
      independent risk factor for ICU mortality (aOR 1.4 [1.1-1.8]; P < 0.02), 28-day
      mortality (aOR 1.3 [1.1-1.7]; P = 0.04) and hospital mortality (aOR 1.9 [1.5
      2.5]; P < 0.001). CONCLUSIONS: Co-infection in critically ill patients with
      influenza has increased in recent years. In this Spanish cohort, age and
      immunosuppression were risk factors for co-infection, and co-infection was an
      independent risk factor for ICU, 28-day and hospital mortality.

PMID- 27709267
TI  - TIMAP repression by TGFbeta and HDAC3-associated Smad signaling regulates
      macrophage M2 phenotypic phagocytosis.
AB  - : TIMAP (TGFbeta-inhibited membrane-associated protein) is an endothelium
      enriched TGFbeta downstream protein and structurally belongs to the targeting
      subunit of myosin phosphatase; however, the mechanism of TGFbeta repressing TIMAP
      and its functional relevance to TGFbeta bioactivity remain largely unknown. Here,
      we report that TIMAP is reduced in TGFbeta-elevated mouse fibrotic kidney and
      highly expressed in macrophages. TGFbeta repression of TIMAP is associated with
      HDAC3 upregulation and its recruitment by Smad2/3 at the Smad binding element on
      TIMAP promoter, whereas specific HDAC3 inhibition reversed the TIMAP repression,
      suggesting that TGFbeta transcriptionally downregulates TIMAP through HDAC3
      associated Smad signaling. Further investigation showed that TIMAP over
      expression interrupted TGFbeta-associated Smad signaling and TIMAP repression by
      TGFbeta correlated with TGFbeta-induced macrophage M2 polarization markers,
      migration, and phagocytosis-the processes promoted by phosphorylation of the
      putative TIMAP substrate myosin light chain (MLC). Consistently, TIMAP
      dephosphorylated MLC in macrophages and TGFbeta induced macrophage migration and
      phagocytosis in TIMAP- and MLC phosphorylation-dependent manners, suggesting that
      TIMAP dephosphorylation of MLC constitutes an essential regulatory loop
      mitigating TGFbeta-associated macrophage M2 phenotypic activities. Given that
      hyperactive TGFbeta often causes excessive macrophage phagocytic activities
      potentially leading to various chronic disorders, the strategies targeting
      HDAC3/TIMAP axis might improve TGFbeta-associated pathological processes. KEY
      MESSAGE: TIMAP is enriched in the endothelium and highly expressed in
      macrophages. TIMAP is suppressed by TGFbeta via HDAC3-associated Smad signaling.
      TIMAP inhibits TGFbeta signaling and TGFbeta-associated macrophage M2
      polarization. TIMAP dephosphorylation of MLC counteracts TGFbeta-induced
      macrophage phagocytosis.

PMID- 27709266
TI  - Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3.
AB  - : Although it is generally believed that nicotine accounts for the beneficial
      effect of smoking on ulcerative colitis, the underlying mechanisms remain not
      well understood. Our previous finding that nicotine inhibits inflammatory
      responses through inducing miR-124 prompted us to ask whether the miRNA is
      involved in the protective action of nicotine against UC. Our present study found
      that miR-124 expression is upregulated in colon tissues from UC patients and DSS
      colitis mice. Nicotine treatment further augmented miR-124 expression in
      lymphocytes isolated from human ulcerative colonic mucosa and ulcerative colon
      tissues from DSS mice, both in infiltrated lymphocytes and epithelial cells.
      Moreover, knockdown of miR-124 significantly diminished the beneficial effect of
      nicotine on murine colitis and IL-6-treated Caco-2 colon epithelial cells.
      Further analysis indicated that nicotine inhibited STAT3 activation in vivo and
      in IL-6 treated Caco-2 cells and Jurkat human T lymphocytes, in which miR-124
      knockdown led to increased activation of STAT3. Blocking STAT3 activity alone is
      beneficial for DSS colitis and also abolished nicotine's protective effect in
      this model. These data indicate that nicotine exerts its protective action in UC
      through inducing miR-124 and inhibiting STAT3, and suggest that the miR-124/STAT3
      system is a potential target for the therapeutic intervention of UC. KEY MESSAGE:
      Nicotine upregulates miR-124 expression in ulcerative colon tissues and cells.
      MiR-124 is required for the protective role of nicotine in DSS colitis mice and
      epithelial cells. The protective effect of nicotine in murine DSS colitis depends
      on blocking STAT3 activation. MiR-124 mediates the inhibitory role of nicotine on
      STAT3/p-STAT3. Targeting miR-124 and STAT3 represents a novel approach for
      treating ulcerative colitis.

PMID- 27709268
TI  - The neuronal metabolite NAA regulates histone H3 methylation in oligodendrocytes
      and myelin lipid composition.
AB  - The neuronal mitochondrial metabolite N-acetylaspartate (NAA) is decreased in the
      multiple sclerosis (MS) brain. NAA is synthesized in neurons by the enzyme N
      acetyltransferase-8-like (NAT8L) and broken down in oligodendrocytes by
      aspartoacylase (ASPA) into acetate and aspartate. We have hypothesized that NAA
      links the metabolism of axons with oligodendrocytes to support myelination. To
      test this hypothesis, we performed lipidomic analyses using liquid chromatography
      tandem mass spectrometry (LC-MS/MS) and high-performance thin-layer
      chromatography (HPTLC) to identify changes in myelin lipid composition in
      postmortem MS brains and in NAT8L knockout (NAT8L-/-) mice which do not
      synthesize NAA. We found reduced levels of sphingomyelin in MS normal appearing
      white matter that mirrored decreased levels of NAA. We also discovered decreases
      in the amounts of sphingomyelin and sulfatide lipids in the brains of NAT8L-/-
      mice compared to controls. Metabolomic analysis of primary cultures of
      oligodendrocytes treated with NAA revealed increased levels of alpha
      ketoglutarate, which has been reported to regulate histone demethylase activity.
      Consistent with this, NAA treatment resulted in alterations in the levels of
      histone H3 methylation, including H3K4me3, H3K9me2, and H3K9me3. The H3K4me3
      histone mark regulates cellular energetics, metabolism, and growth, while H3K9me3
      has been linked to alterations in transcriptional repression in developing
      oligodendrocytes. We also noted the NAA treatment was associated with increases
      in the expression of genes involved in sulfatide and sphingomyelin synthesis in
      cultured oligodendrocytes. This is the first report demonstrating that neuronal
      derived NAA can signal to the oligodendrocyte nucleus. These data suggest that
      neuronal-derived NAA signals through epigenetic mechanisms in oligodendrocytes to
      support or maintain myelination.

PMID- 27709270
TI  - SHP-2 phosphatase controls aryl hydrocarbon receptor-mediated ER stress response
      in mast cells.
AB  - Previously we reported that exposure of mouse and human mast cells to aryl
      hydrocarbon receptor (AhR) ligands resulted in reactive oxygen species (ROS)- and
      calcium (Ca2+)-dependent activation of mast cells in vitro and in vivo. However,
      the mechanisms through which the AhR-ligand axis mediates stress response, Ca2+
      signaling and subsequent mast cell activation remain to be fully elucidated.
      Evidence is provided herein that SHP-2 is critical in regulating AhR-mediated ER
      stress response and intracellular Ca2+ dynamics. We found that an AhR ligand,
      FICZ, induced significant reduction of intracellular GSH and an increased level
      of intracellular ROS. Significantly, we showed that in FICZ-treated mast cells,
      SHP-2 promoted, in a ROS-dependent manner, ER stress response involving primarily
      the PERK signaling pathway, ATF4 activation and eIF2alpha phosphorylation, which
      could be reversed by the addition of an antioxidant, NAC, and was inhibited in
      cells with SHP-2 knockdown. Our findings suggested that SHP-2 is critical in
      controlling ER stress signals in response to AhR activation, which provides a new
      mechanistic insight into how the AhR-ligand axis regulates cellular adaptation to
      the environmental insult in mast cells.

PMID- 27709271
TI  - Letter in response to the letter to the editor of archives of toxicology by
      Woegerbauer et al. (2016).

PMID- 27709269
TI  - Can augmented feedback facilitate learning a reactive balance task among older
      adults?
AB  - While concurrent augmented visual feedback of the center of pressure (COP) or
      center of gravity (COG) can improve quiet standing balance control, it is not
      known whether such feedback improves reactive balance control. Additionally, it
      is not known whether feedback of the COP or COG is superior. This study aimed to
      determine whether (1) concurrent augmented feedback can improve reactive balance
      control, and (2) feedback of the COP or COG is more effective. Forty-eight
      healthy older adults (60-75 years old) were randomly allocated to one of three
      groups: feedback of the COP, feedback of the COG, or no feedback. The task was to
      maintain standing while experiencing 30 s of continuous pseudo-random
      perturbations delivered by a moving platform. Participants completed 25 trials
      with or without feedback (acquisition), immediately followed by 5 trials without
      feedback (immediate transfer); 5 trials without feedback were completed after a
      24-h delay (delayed transfer). The root mean square error (RMSE) of COP-COG,
      electrodermal level, and co-contraction index were compared between the groups
      and over time. All three groups reduced RMSE and co-contraction index from the
      start of the acquisition to the transfer tests, and there were no significant
      between-group differences in RMSE or co-contraction on the transfer tests.
      Therefore, all three groups learned the task equally well, and improved balance
      was achieved with practice via a more efficient control strategy. The two
      feedback groups reduced electrodermal level with practice, but the no-feedback
      group did not, suggesting that feedback may help to reduce anxiety.

PMID- 27709272
TI  - In vivo cardiomyocyte response to YTX- and AZA-1-induced damage: autophagy versus
      apoptosis.
AB  - Yessotoxins (YTX) and azaspiracids (AZAs) are marine toxins produced by
      phytoplanktonic dinoflagellates that get accumulated in filter feeding shellfish
      and finally reach human consumers through the food web. Both toxin classes are
      worldwide distributed, and food safety authorities have regulated their content
      in shellfish in many countries. Recently, YTXs and AZAs have been described as
      compounds with subacute cardiotoxic potential in rats owed to alterations of the
      cardiovascular function and ultrastructural heart damage. These molecules are
      also well known in vitro inducers of cell death. The aim of this study was to
      explore the presence of cardiomyocyte death after repeated subacute exposure of
      rats to AZA-1 and YTX for 15 days. Because autophagy and apoptosis are often
      found in dying cardiomyocytes, several autophagic and apoptotic markers were
      determined by western blot in heart tissues of these rats. The results showed
      that hearts from YTX-treated rats presented increased levels of the autophagic
      markers microtubule-associated protein light chain 3-II (LC3-II) and beclin-1,
      nevertheless AZA-1-treated hearts evidenced increased levels of the apoptosis
      markers cleaved caspase-3 and -8, cleaved PARP and Fas ligand. Therefore, while
      YTX-induced damage to the heart triggers autophagic processes, apoptosis
      activation occurs in the case of AZA-1. For the first time, activation of cell
      death signals in cardiomyocytes is demonstrated for these toxins with in vivo
      experiments, which may be related to alterations of the cardiovascular function.

PMID- 27709273
TI  - Impact of a Novel Bioabsorbable Implant on Radiation Treatment Planning for
      Breast Cancer.
AB  - BACKGROUND: Techniques for accurately delineating the tumor bed after breast
      conserving surgery (BCS) can be challenging. As a result, the accuracy, and
      efficiency of radiation treatment (RT) planning can be negatively impacted.
      Surgically placed clips or the post-surgical seroma are commonly used to
      determine target volume; however, these methods can lead to a high degree of
      uncertainty and variability. A novel 3-dimensional bioabsorbable marker was used
      during BCS and assessed for its impact on RT planning. METHODS: One hundred and
      ten implants were sutured to the margins of the tumor bed excision site in 108
      patients undergoing BCS. Routine CT imaging of the breast tissue was performed
      for RT planning, and the marker was assessed for visibility and utility in target
      delineation. RT regimens, target volumes and associated treatment costs were
      analyzed. RESULTS: In all patients, the marker was easily visible and in 95.7 %
      of cases, it proved useful for RT planning. 36.8 % of patients received
      conventional whole breast irradiation plus boost, 56.6 % received hypo
      fractionation plus boost, and 6.6 % received accelerated partial breast
      irradiation. A shift toward increased use of hypo-fractionated regimens was noted
      over the three year period of this study. There were no device-related
      complications or cancer recurrences in this group of patients. CONCLUSIONS: This
      study demonstrated the use of a novel 3-dimensional marker as a safe and
      effective method for delineating the tumor bed with a significant utility for RT
      planning. With routine use of the device, an increased use of hypofractionation
      with a resultant 25 % cost savings was noted.

PMID- 27709274
TI  - [Injuries to blood vessels near the heart caused by central venous catheters].
AB  - Injuries to blood vessels near the heart can quickly become life-threatening and
      include arterial injuries during central venous puncture, which can lead to
      hemorrhagic shock. We report 6 patients in whom injury to the subclavian artery
      and vein led to life-threatening complications. Central venous catheters are
      associated with a multitude of risks, such as venous thrombosis, air embolism,
      systemic or local infections, paresthesia, hemothorax, pneumothorax, and cervical
      hematoma, which are not always immediately discernible. The subclavian catheter
      is at a somewhat lower risk of catheter-associated sepsis and symptomatic venous
      thrombosis than approaches via the internal jugular and femoral veins. Indeed,
      access via the subclavian vein carries a substantial risk of pneumo- and
      hemothorax. Damage to the subclavian vein or artery can also occur during
      deliberate and inadvertent punctures and result in life-threatening
      complications. Therefore, careful consideration of the access route is required
      in relation to the patient and the clinical situation, to keep the incidence of
      complications as low as possible. For catheterization of the subclavian vein,
      puncture of the axillary vein in the infraclavicular fossa is a good alternative,
      because ultrasound imaging of the target vessel is easier than in the subclavian
      vein and the puncture can be performed much further from the lung.

PMID- 27709275
TI  - [Impairment of oxygenation of patients in surgical intensive care : Early symptom
      of severe sepsis].
AB  - BACKGROUND: Sepsis and septic shock are major contributors to morbidity and
      mortality in intensive care patients. Early identification and adequate therapy
      are of utmost importance to reduce the still high mortality in patients with
      severe sepsis. Many of the pathophysiologic changes are nonspecific. Thus, a
      combination of symptoms and laboratory results are necessary to confirm the
      diagnosis. Impairment of the Horovitz index is identified as being a primal
      prognostic criterion for early diagnosis in serious progression of sepsis, after
      exclusion of a few differential diagnoses. Based on this fact, the prevalence of
      this symptom compared to other sepsis parameters is of specific interest. METHOD:
      In a retrospective study 33 cases of serious sepsis were analysed during the
      patient's course of intensive care treatment focusing on oxygenation. The
      deterioration of oxygenation, meaning a drop in the Horovitz index below 200 mm
      Hg (25.7 kPa) or a decrease in paO2 by 67.5 mm Hg (9 kPa) in spontaneously
      breathing patients with sepsis was the mean inclusion criteria. We compared the
      sequence of occurrence of known sepsis markers (e. g. PCT, WBC, CRP) with the
      deterioration in oxygenation to answer the question whether impairment of
      oxygenation could be an early symptom of severe sepsis. The Mann Whitney U-test
      and a discriminant analysis were performed to verify differences of the variables
      investigated between surviving and deceased patients. Furthermore a regression
      analysis was performed to confirm the results of the discriminant analysis.
      RESULTS: The mean drop in the Horovitz index was 90 +/- 24 mm Hg (12 +/- 3.2 kPa)
      within 4.5 h respectively. This was highly significant (p < 0.001). In all
      patients impairment of oxygenation indicated an individual onset and further
      progression of a serious sepsis. In more than 3/4 of all cases this symptom
      occurred in an earlier stage than other organ dysfunctions. In 79 % of cases,
      patients showed an impairment of oxygenation before PCT increased on values of >2
      ng/ml. In 76 % of cases impairment of oxygenation occurred earlier than all other
      investigated parameters. Significant differences were found between surviving and
      deceased patients regarding to their age as well as the timeframe from the
      beginning of impaired oxygenation to the onset of the effect of the administered
      antibiotics. These two parameters (age, time to sufficient antibiotic therapy)
      were confirmed by regression analysis and showing similar effect coefficients,
      age 1.09 and time to sufficient antibiotic therapy 1.04 respectively. CONCLUSION:
      An urgent worsening of pulmonary function in patients in intensive care requires
      immediate differential diagnostics due to substantial therapeutic consequences.
      Our results confirm that impairment of pulmonary oxygenation is the first
      prognostic symptom of severe onset of sepsis. Consequently, we recommend that
      this parameter be considered in diagnostic staging. After exclusion of a few
      differential diagnoses impairment of oxygenation can be the very first symptom of
      severe sepsis. The patient's age and time to sufficient antibiotic therapy are
      two very important prognostic factors with respect to mortality. Early and
      sufficient antibiotic therapy, and in a few cases surgical intervention are of
      utmost importance.

PMID- 27709276
TI  - The intervertebral disc, the endplates and the vertebral bone marrow as a unit in
      the process of degeneration.
AB  - OBJECTIVES: The association of disc degeneration (DD) and vertebral endplate
      degeneration (EPD) is still not well understood. This study aimed to find
      segmental predictive risk factors for DD and EPD and to illuminate associations
      of the disc, endplate and bone marrow changes in the process of degeneration.
      METHODS: After institutional review board approval, 450 lumbar levels, followed
      up with MRI for at least 4 years, were retrospectively graded for DD according to
      Pfirrmann (PFG), for EPD according to the endplate score (EPS) and according to
      the presence, extension and type of Modic changes (MC). Clustered logistic
      regression and multivariate analysis was applied in nested, matched case-control
      subgroups to evaluate potential local risk factors for progression. RESULTS: An
      EPS score of  >=4 was identified as an independent risk factor for progression of
      DD (OR = 2.32, 95%CI:1.07-5.01,p = 0.03) and MC (OR = 5.49,95%CI:2.30-13.10,p <
      0.001). Progression of DD was significantly accompanied by progression or
      evolution of MC (OR = 12.25,95%CI:1.49-100.6,p = 0.02) and with progression of
      EPS (OR = 1.71, 95%CI:1.00-1.05, p = 0.01). Once advanced DD has occurred, it
      becomes a risk factor for progression in EPS (OR = 2.24,95%CI:1.23-4.12,p <
      0.01). CONCLUSIONS: The degenerative processes in the disc, endplate and bone
      marrow are highly associated. An EPS >= 4 is an independent risk factor for DD
      and MC progression in a population with low back pain. KEY POINTS: * The
      degenerative processes in the disc, endplate and bone marrow are associated. * An
      endplate score >=4 is a risk factor for DD and MC progression. * Modic changes
      are last to occur in the development of segmental intervertebral degeneration. *
      A new segmental grading system is suggested.

PMID- 27709277
TI  - Diffusion-weighted MR enterography for evaluating Crohn's disease: Effect of anti
      peristaltic agent on the diagnosis of bowel inflammation.
AB  - OBJECTIVES: To prospectively investigate how Buscopan affects the diagnosis of
      bowel inflammation by diffusion-weighted imaging MR enterography (DWI-MRE) in
      Crohn's disease (CD). METHODS: Thirty CD patients without previous bowel surgery
      underwent DWI-MRE (b = 900 sec/mm2) before and after intravenous Buscopan. The 30
      patients were randomly divided into two groups; using a crossover design,
      interpretations were made regarding the presence of restricted mural diffusion
      (i.e., bowel inflammation) in nine bowel segments in two separate reading
      sessions by two readers. The readers also judged restricted mural diffusion
      extent in each bowel segment on two side-by-side DWI-MRE images with a random
      right-to-left order. Ileocolonoscopy and conventional MRE interpreted by an
      expert panel were reference standards. RESULTS: We analyzed 262 bowel segments.
      DWI-MRE without Buscopan significantly decreased sensitivity for both readers
      (58.8 % vs. 72.9 %, P = 0.046; 57.6 % vs. 85.9 %, P = 0.001) and did not
      significantly increase specificity (P = 0.085 and 0.396). Two readers noted that
      28.6 % and 23.3 % of 262 bowel segments had greater diffusion restriction extent
      on DWI-MRE with Buscopan compared with DWI-MRE without Buscopan (P < 0.001) and
      68.7 % and 74 %, respectively, had similar extent between them. CONCLUSION:
      Omitting Buscopan caused a greater loss in sensitivity of DWI-MRE than false
      positive reduction for diagnosing bowel inflammation in CD. KEY POINTS: *
      Omitting Buscopan significantly decreases DWI-MRE sensitivity for diagnosing
      bowel inflammation in CD. * Increase in the corresponding DWI-MRE specificity by
      omitting Buscopan is less apparent. * DWI-MRE without Buscopan underestimates the
      extent of bowel inflammation in CD.

PMID- 27709278
TI  - Trends and patterns of computed tomography scan use among children in The
      Netherlands: 1990-2012.
AB  - OBJECTIVE: To evaluate trends and patterns in CT usage among children (aged 0-17
      years) in The Netherlands during the period 1990-2012. METHODS: Lists of
      electronically archived paediatric CT scans were requested from the Radiology
      Information Systems (RIS) of Dutch hospitals which reported >10 paediatric CT
      scans annually in a survey conducted in 2010. Data included patient
      identification, birth date, gender, scan date and body part scanned. For non
      participating hospitals and for years prior to electronic archiving in some
      participating hospitals, data were imputed by calendar year and hospital type
      (academic, general with <500 beds, general with >= 500 beds). RESULTS: Based on
      236,066 CT scans among 146,368 patients performed between 1990 and 2012,
      estimated annual numbers of paediatric CT scans in The Netherlands increased from
      7,731 in 1990 to 26,023 in 2012. More than 70 % of all scans were of the head and
      neck. During the last decade, substantial increases of more than 5 % per year
      were observed in general hospitals with fewer than 500 beds and among children
      aged 10 years or older. CONCLUSION: The estimated number of paediatric CT scans
      has more than tripled in The Netherlands during the last two decades. KEY POINTS:
      * Paediatric CT in The Netherlands has tripled during the last two decades. * The
      number of paediatric CTs increased through 2012 in general hospitals. *
      Paediatric CTs continued to increase among children aged 10 years or older.

PMID- 27709279
TI  - Substantia nigra fractional anisotropy is not a diagnostic biomarker of
      Parkinson's disease: A diagnostic performance study and meta-analysis.
AB  - OBJECTIVES: Our goal was to estimate the diagnostic accuracy of substantia nigra
      fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample
      similar to the clinical setting, including patients with essential tremor (ET)
      and healthy controls (HC). We also performed a systematic review and meta
      analysis to estimate mean change in SN-FA induced by PD and its diagnostic
      accuracy. METHODS: Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC.
      To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI
      results of this sample were pooled into a meta-analysis that included 1,432
      subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic
      accuracy measures. RESULTS: In our sample, we did not observe a significant
      effect of disease on SN-FA and it was uninformative for diagnosis. The results of
      the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC
      (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD
      was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI:
      58-70), respectively. There was high heterogeneity between studies (I2 = 91.9 %).
      CONCLUSIONS: SN-FA cannot be used as an isolated measure to diagnose PD. KEY
      POINTS: * SN-FA appears insufficiently sensitive and specific to diagnose PD. *
      Radiologists must be careful when translating mean group results to clinical
      practice. * Imaging protocol and analysis standardization is necessary for
      developing reproducible quantitative biomarkers.

PMID- 27709280
TI  - High rates of clinically relevant incidental findings by total-body CT scanning
      in trauma patients; results of the REACT-2 trial.
AB  - OBJECTIVES: To determine whether there is a difference in frequency and clinical
      relevance of incidental findings detected by total-body computed tomography
      scanning (TBCT) compared to those by the standard work-up (STWU) with selective
      computed tomography (CT) scanning. METHODS: Trauma patients from five trauma
      centres were randomized between April 2011 and January 2014 to TBCT imaging or
      STWU consisting of conventional imaging with selective CT scanning. Incidental
      findings were divided into three categories: 1) major finding, may cause
      mortality; 2) moderate finding, may cause morbidity; and 3) minor finding, hardly
      relevant. Generalized estimating equations were applied to assess differences in
      incidental findings. RESULTS: In total, 1083 patients were enrolled, of which 541
      patients (49.9 %) were randomized for TBCT and 542 patients (50.1 %) for STWU.
      Major findings were detected in 23 patients (4.3 %) in the TBCT group compared to
      9 patients (1.7 %) in the STWU group (adjusted rate ratio 2.851; 95%CI 1.337
      6.077; p < 0.007). Findings of moderate relevance were detected in 120 patients
      (22.2 %) in the TBCT group compared to 86 patients (15.9 %) in the STWU group
      (adjusted rate ratio 1.421; 95%CI 1.088-1.854; p < 0.010). CONCLUSIONS: Compared
      to selective CT scanning, more patients with clinically relevant incidental
      findings can be expected by TBCT scanning. KEY POINTS: * Total-body CT scanning
      in trauma results in 1.5 times more incidental findings. * Evaluation by TBCT in
      trauma results in more patients with incidental findings. * In every category of
      clinical relevance, TBCT detects more incidental findings.

PMID- 27709281
TI  - Stratifying fibrinolytic dosing in pediatric parapneumonic effusion based on
      ultrasound grade correlation.
AB  - BACKGROUND: Complicated pleural effusion prolongs the hospital course of
      pneumonia. Chest tube placement with instillation of fibrinolytic medication
      allows efficient drain output and decreases hospital stay. OBJECTIVE: To evaluate
      experience with lower fibrinolytic dose for parapneumonic effusions and to assess
      potential dose stratification based on a simple ultrasound grading system.
      MATERIALS AND METHODS: We retrospectively reviewed the medical record to identify
      children and young adults who received fibrinolytic therapy for parapneumonic
      effusion and had chest tube placement by an interventional radiology service at a
      single children's hospital. We assessed tissue plasminogen activator (tPA) dosing
      and treatment duration, as well as the need for a second pleural procedure or
      surgical drainage. Diagnostic US images were classified as showing less than 50%
      pleural echogenicity (grade 1) or greater than 50% pleural echogenicity (grade 2)
      and were correlated with clinical parameters. RESULTS: Of 32 patients with
      parapneumonic effusion, all except one received at least some 1-mg tPA doses.
      Dosing was solely 1-mg tPA in 81% of subjects; 19% of subjects also received 2-mg
      tPA doses. Mean fibrinolytic duration was 3.1 days for grade 1 effusions compared
      to 5.4 days for grade 2 effusions. A second pleural procedure was required in
      15.6% of children. Pleural drainage with fibrinolytic therapy was successful in
      97%; only one child required surgical drainage. Grade 2 US differed significantly
      from grade 1 US, with grade 2 occurring in younger patients (P < 0.0001), smaller
      patients (P < 0.0001), those needing a second procedure (P = 0.001), those with
      positive pleural culture or polymerase chain reaction test (P = 0.006), and those
      with longer treatment duration (P = 0.03). CONCLUSION: A lower 1-mg dosing
      regimen of tissue plasminogen activator was effective in all children with less
      complex (grade 1 US imaging) parapneumonic effusions. Grade 2 US images
      correlated with younger and smaller children, presence of a pleural organism, and
      longer or more complicated chest tube duration.

PMID- 27709283
TI  - Post-treatment with cotinine improved memory and decreased depressive-like
      behavior after chemotherapy in rats.
AB  - PURPOSE: Most cancer patients treated with systemic adjuvant chemotherapy endure
      long-lasting side effects including decrease in concentration, forgetfulness and
      slower thinking, which are globally termed "chemobrain." Cotinine, the main
      derivative of nicotine, improved visual and spatial working memory and decreased
      depressive-like behavior in an animal model of chemotherapy-induced cognitive
      impairment. METHODS: In this study, we investigated the effect of cotinine on
      weight gain, locomotor activity, cognitive abilities and depressive-like behavior
      in rats treated with the chemotherapy mix, cyclophosphamide, methotrexate and 5
      fluorouracil. Locomotor activity and depressive-like behavior were assessed using
      the rotarod and Porsolt's tests, respectively. Changes in cognitive abilities
      were determined using the novel place recognition test. RESULTS: Female rats
      treated with cotinine after chemotherapy, recovered weight faster, showed
      superior cognitive abilities and lower levels of depressive-like behavior than
      chemotherapy, vehicle-treated rats. CONCLUSIONS: This evidence suggests that
      treatment with cotinine may facilitate the recovery and diminish the cognitive
      consequences of chemotherapy.

PMID- 27709282
TI  - Effect of veliparib (ABT-888) on cardiac repolarization in patients with advanced
      solid tumors: a randomized, placebo-controlled crossover study.
AB  - PURPOSE: Veliparib (ABT-888) is an orally bioavailable potent inhibitor of
      poly(ADP-ribose) polymerase (PARP)-1 and PARP-2. This phase 1 study evaluated the
      effect of veliparib on corrected QT interval using Fridericia's formula (QTcF).
      METHODS: Eligible patients with advanced solid tumors received single-dose oral
      veliparib (200 mg or 400 mg) or placebo in a 6-sequence, 3-period crossover
      design. The primary endpoint was the difference in the mean baseline-adjusted
      QTcF between 400 mg veliparib and placebo (??QTcF) at six post-dose time points.
      Absence of clinically relevant QTcF effect was shown if the 95 % upper confidence
      bound (UCB) for the mean ??QTcF was <10 ms for all time points. An exposure
      response analysis was also performed. RESULTS: Forty-seven patients were
      enrolled. Maximum mean ??QTcF of veliparib 400 mg was 6.4 ms, with a 95 % UCB of
      8.9 ms; for veliparib 200 mg, the maximum mean ??QTcF was 3.6 ms, with a 95 % UCB
      of 6.1 ms. No patient had a QTcF value >480 ms or change from baseline in QTcF
      interval >30 ms. Treatment-emergent adverse events (TEAEs) were experienced by
      36.2, 48.9, and 47.8 % of patients while receiving veliparib 200 mg, veliparib
      400 mg, and placebo, respectively. Most common TEAEs were nausea (12.8 %) and
      myalgia (8.5 %) after veliparib 200 mg, nausea (8.5 %) and vomiting (8.5 %) after
      veliparib 400 mg, and nausea (6.5 %) after placebo. CONCLUSIONS: Single-dose
      veliparib (200 mg or 400 mg) did not result in clinically significant QTc
      prolongation and was well tolerated in patients with advanced solid tumors.

PMID- 27709284
TI  - Population pharmacokinetic-pharmacodynamic modeling and model-based prediction of
      docetaxel-induced neutropenia in Japanese patients with non-small cell lung
      cancer.
AB  - PURPOSE: Docetaxel is used to treat many cancers, and neutropenia is the dose
      limiting factor for its clinical use. A population pharmacokinetic
      pharmacodynamic (PK-PD) model was introduced to predict the development of
      docetaxel-induced neutropenia in Japanese patients with non-small cell lung
      cancer (NSCLC). METHODS: Forty-seven advanced or recurrent Japanese patients with
      NSCLC were enrolled. Patients received 50 or 60 mg/m2 docetaxel as monotherapy,
      and blood samples for a PK analysis were collected up to 24 h after its infusion.
      Laboratory tests including absolute neutrophil count data and demographic
      information were used in population PK-PD modeling. The model was built by NONMEM
      7.2 with a first-order conditional estimation using an interaction method. Based
      on the final model, a Monte Carlo simulation was performed to assess the impact
      of covariates on and the predictability of neutropenia. RESULTS: A three
      compartment model was employed to describe PK data, and the PK model adequately
      described the docetaxel concentrations observed. Serum albumin (ALB) was detected
      as a covariate of clearance (CL): CL (L/h) = 32.5 * (ALB/3.6)0.965 *
      (WGHT/70)3/4. In population PK-PD modeling, a modified semi-mechanistic
      myelosuppression model was applied, and characterization of the time course of
      neutrophil counts was adequate. The covariate selection indicated that alpha1
      acid glycoprotein (AAG) was a predictor of neutropenia. The model-based
      simulation also showed that ALB and AAG negatively correlated with the
      development of neutropenia and that the time course of neutrophil counts was
      predictable. CONCLUSION: The developed model may facilitate the prediction and
      care of docetaxel-induced neutropenia.

PMID- 27709285
TI  - Effect of low pH start-up on continuous mixed-culture lactic acid fermentation of
      dairy effluent.
AB  - Mixed-culture fermentation that does not require an energy-intensive
      sterilization process is a viable approach for the economically feasible
      production of lactic acid (LA) due to the potential use of organic waste as
      feedstock. This study investigated mixed-culture LA fermentation of whey, a high
      strength organic wastewater, in continuous mode. Variations in the hydraulic
      retention time (HRT) from 120 to 8 h under different pH regimes in two
      thermophilic reactors (55  degrees C) were compared for their fermentation
      performance. One reactor was maintained at a low pH (pH 3.0) during operation at
      HRTs of 120 to 24 h and then adjusted to pH 5.5 in the later phases of
      fermentation at HRTs of 24 to 8 h (R1), while the second reactor was maintained
      at pH 5.5 throughout the experiment (R2). Although the LA production in R1 was
      negligible at low pH, it increased dramatically after the pH was raised to 5.5
      and exceeded that in R2 when stabilized at HRTs of 8 and 12 h. The maximum yield
      (0.62 g LA/g substrate fed as the chemical oxygen demand (COD) equivalent), the
      production rate (11.5 g/L day), and the selectivity (95 %) of LA were all
      determined at a 12-h HRT in R1. Additionally, molecular and statistical analyses
      revealed that changes in the HRT and the pH significantly affected the bacterial
      community structure and thus the fermentation characteristics of the experimental
      reactors. Bacillus coagulans was likely the predominant LA producer in both
      reactors. The overall results suggest that low pH start-up has a positive effect
      on yield and selectivity in mixed-culture LA fermentation.

PMID- 27709286
TI  - Effects of deep sea water and Lactobacillus paracasei subsp. paracasei NTU 101 on
      hypercholesterolemia hamsters gut microbiota.
AB  - Hypercholesterolemia is a common metabolic syndrome in modern human society.
      Despite that the alteration of host gut microbiota has been linked to
      hypercholesterolemia in previous studies, the key host-microbiota interaction of
      hypercholesterolemia remains elusive. Lactobacillus paracasei subsp. paracasei
      NTU 101 (NTU 101) and deep sea water (DSW) were known for cholesterol-lowering
      potential. The impact of NTU 101 and DSW on hamster gut microbiota was
      investigated side-by-side using denaturing gradient gel electrophoresis (DGGE)
      and metagenomic analysis in this study. These two cholesterol-lowering substances
      altered hamster cecal microbiota in a very different way with similar cholesterol
      lowering effects. Bacteroidetes was the only bacterial population that
      significantly correlated to host lipid profile (serum total cholesterol and serum
      low-density lipoprotein). Allobaculum and Clostridium XIVa were associated with
      beneficial effect of NTU 101. Parasutterella was only associated with consumption
      of DSW. The major bacterial taxa Akkermansia is associated with high-cholesterol
      diet but not host cholesterol level. This phenomenon suggested that cholesterol
      lowering effect is not necessarily linked to specific bacteria-host interaction,
      and the conclusion of causal relationships among bacterial abundance, diet, and
      host physiology should be more rigorously investigated.

PMID- 27709287
TI  - Biological treatment of actual petrochemical wastewater using
      anaerobic/anoxic/oxic process and the microbial diversity analysis.
AB  - A novel process integrating anaerobic hydrolysis-acidification (HA) and
      anoxic/oxic (A/O) reactors was developed to treat the actual petrochemical
      wastewater, which was operated for more than 8 months, the removal efficiency of
      COD and NH4+-N was monitored, and the microbial community was analyzed. The
      results showed that the effluent concentrations were maintained at around 99 and
      1.3 mg/L, with the removal efficiency of 70.6 and 95.4 %, respectively at a total
      hydraulic retention time (HRT) of 20 h. The major pollutants in the influent were
      identified as hydrocarbons, aldehydes, heterocyclic matters, amines, alcohols,
      phenols, ketones, etc. by GC-MS analysis, while only heterocyclic compounds,
      ketones, and esters were detected in the effluent after HA-A/O treatment.
      Bacteria belonging to phyla Chloroflexi, Proteobacteria, and Bacteroidetes were
      highly enriched in the system. The predominant genera in HA, anoxic, and oxic
      tanks were Anaerolineaceae uncultured and Desulfobacter, Blastocatella and
      Anaerolineaceae uncultured, Saprospiraceae uncultured and Nitrosomonadaceae
      uncultured, respectively. The sulfate-reducing bacteria Desulfobacter,
      Desulfofustis and Desulfomicrobium were detected only in HA reactor. The ammonium
      oxidizing bacteria Nitrosomonadaceae and Nitrosomonas and nitrite-oxidizing
      bacteria Nitrospira were highly enriched in A/O reactor, which is consistent with
      the good nitrification performance.

PMID- 27709288
TI  - Heterologous expression of oxytetracycline biosynthetic gene cluster in
      Streptomyces venezuelae WVR2006 to improve production level and to alter
      fermentation process.
AB  - Heterologous expression is an important strategy to activate biosynthetic gene
      clusters of secondary metabolites. Here, it is employed to activate and
      manipulate the oxytetracycline (OTC) gene cluster and to alter OTC fermentation
      process. To achieve these goals, a fast-growing heterologous host Streptomyces
      venezuelae WVR2006 was rationally selected among several potential hosts. It
      shows rapid and dispersed growth and intrinsic high resistance to OTC. By
      manipulating the expression of two cluster-situated regulators (CSR) OtcR and
      OtrR and precursor supply, the OTC production level was significantly increased
      in this heterologous host from 75 to 431 mg/l only in 48 h, a level comparable to
      the native producer Streptomyces rimosus M4018 in 8 days. This work shows that S.
      venezuelae WVR2006 is a promising chassis for the production of secondary
      metabolites, and the engineered heterologous OTC producer has the potential to
      completely alter the fermentation process of OTC production.

PMID- 27709289
TI  - Enrichment of denitratating bacteria from a methylotrophic denitrifying culture.
AB  - Denitratation (nitrite produced from nitrate), has the potential applications in
      wastewater treatment by combining with ANAMMOX process. The occurrence of
      denitratation has been shown to be effected qualitatively by various parameters
      in the environment. A more quantitative understanding can be obtained using
      enrichment cultures in lab-scale experiments, yet information on the enrichment
      of functional microorganisms responsible for denitratation is lacking. In this
      study, a stable denitratation-dominated culture was obtained from methylotrophic
      denitrifying culture. The results showed that, besides the substitution of
      acetate for methanol, the lasting starvation following saturation of electron
      donor was another pivotal selection pressure that favored the growth of
      denitratating bacteria, which was supported by the distinctive physiological
      strategy involving the higher growth rate combining with larger poly
      hydroxybutyrate (PHB) accumulation at sufficient electron donor situation and
      then manage the stress of electron donor starvation by consumpiton of the PHB.
      High-throughput 16S rRNA gene sequencing analysis indicated that non
      methylotrophic Halomonas campisalis (48.1 %) and Halomonas campaniensis (30.4 %)
      dominated in the denitratating community. Moreover the denitratation was driven
      by the nitrate inhibiting the nirS transcription in the Halomonas species.

PMID- 27709290
TI  - Open versus laparoscopic approach for intestinal malrotation in infants and
      children: a systematic review and meta-analysis.
AB  - PURPOSE: Although the principles of the Ladd's procedure for intestinal
      malrotation in children have remained unchanged since its first description, in
      the era of minimally invasive surgery it is controversial whether laparoscopy is
      advantageous over open surgery. The aim of our study was to determine whether the
      surgical approach for the treatment of malrotation had an impact on patient
      outcome. METHODS: Using a defined strategy (PubMed, Cochrane, Embase and Web of
      Science MeSH headings), two investigators independently searched for studies
      comparing open versus laparoscopic Ladd's procedure in children. Case reports and
      opinion articles were excluded. Outcome measures included age at operation, time
      to full enteral feeding, length of hospital stay, and post-operative
      complications. Maneuvers were compared using Fisher's exact test and meta
      analysis was conducted using RevMan 5.3. Data are expressed as mean +/- SD.
      RESULTS: Of 308 abstracts screened, 49 full-text articles were analyzed and nine
      (all retrospective) met our search criteria. Selected articles included 1003
      patients, of whom 744 (74 %) underwent open surgery and 259 (26 %) laparoscopy.
      Patients who had open surgery were younger (0.9 +/- 1.2 years) than those who
      underwent laparoscopy (2.6 +/- 3 years; p < 0.0001). Laparoscopy was converted to
      open Ladd's in 25.3 % patients. Laparoscopy was associated with faster full
      enteral feeding (1.5 +/- 0.3 days) in comparison to open surgery (4.6 +/- 0.1
      days, p < 0.0001). Length of hospital stay was shorter in the laparoscopic group
      (5.9 +/- 4.3 days) than in the open group (11.2 +/- 6.7 days; p < 0.0001). Open
      surgery was associated with higher overall post-operative complication rate (21
      %) than laparoscopy (8 %; p < 0.0001). Although there was no difference in the
      prevalence of post-operative bowel obstruction (open, n = 10 %; laparoscopy, n =
      0 % p = 0.07), post-operative volvulus was more frequent in the laparoscopy group
      (3.5 %) than in the open group (1.4 %, p = 0.04). CONCLUSION: Comparative but non
      randomized studies indicate that laparoscopic Ladd's procedure is not commonly
      performed in young children. Although one third of laparoscopic procedures is
      converted to open surgery, laparoscopy is associated with shorter time to full
      enteral feeds and length of hospital stay. However, laparoscopic Ladd's procedure
      seems to have higher incidence of post-operative volvulus. Prospective randomized
      studies with long follow-up are needed to confirm present outcome data and
      determine the safety and effectiveness of the laparoscopic approach.

PMID- 27709291
TI  - Influence of Gender on Epidemiology and Clinical Manifestations of Sarcoidosis: A
      Population-Based Retrospective Cohort Study 1976-2013.
AB  - PURPOSE: The influence of ethnicity on epidemiology and clinical manifestations
      of sarcoidosis is well recognized. However, data on the role of sex are limited.
      METHODS: The current study utilized the resource of the Rochester Epidemiology
      Project to identify all residents of Olmsted County, Minnesota, United States,
      with new diagnosis of sarcoidosis from 1976 to 2013. Diagnosis was verified by
      medical record and histopathological report review. RESULTS: 345 incident cases
      of sarcoidosis were identified: 174 (50 %) were female and 171 (50 %) were male.
      The age at diagnosis was significantly higher among females than males (48.3 vs.
      42.8 years; p < 0.001). Intra-thoracic disease was seen in the great majority of
      patients (98 % among females and 96 % among males; p = 0.50). However, pulmonary
      symptoms were significantly more frequent among males than females (51 vs. 36 %;
      p = 0.006). The frequency of individual extra-thoracic organ involvement was not
      significantly different between females and males except for cutaneous
      involvement and uveitis that were significantly more common among females (6 vs.
      1 % for uveitis, p = 0.012 and 25 vs. 12 % for cutaneous involvement, p = 0.002).
      The frequency of elevate angiotensin-converting enzyme level and hypercalcemia
      was not significantly different between the two sexes. CONCLUSIONS: Females
      tended to be older at the age they developed sarcoidosis, and had more uveitis
      and cutaneous involvement than males.

PMID- 27709292
TI  - Acoustic analysis of snoring sounds recorded with a smartphone according to
      obstruction site in OSAS patients.
AB  - Snoring is a sign of increased upper airway resistance and is the most common
      symptom suggestive of obstructive sleep apnea. Acoustic analysis of snoring
      sounds is a non-invasive diagnostic technique and may provide a screening test
      that can determine the location of obstruction sites. We recorded snoring sounds
      according to obstruction level, measured by DISE, using a smartphone and focused
      on the analysis of formant frequencies. The study group comprised 32 male
      patients (mean age 42.9 years). The spectrogram pattern, intensity (dB),
      fundamental frequencies (F 0), and formant frequencies (F 1, F 2, and F 3) of the
      snoring sounds were analyzed for each subject. On spectrographic analysis,
      retropalatal level obstruction tended to produce sharp and regular peaks, while
      retrolingual level obstruction tended to show peaks with a gradual onset and
      decay. On formant frequency analysis, F 1 (retropalatal level vs. retrolingual
      level: 488.1 +/- 125.8 vs. 634.7 +/- 196.6 Hz) and F 2 (retropalatal level vs.
      retrolingual level: 1267.3 +/- 306.6 vs. 1723.7 +/- 550.0 Hz) of retrolingual
      level obstructions showed significantly higher values than retropalatal level
      obstruction (p < 0.05). This suggests that the upper airway is more severely
      obstructed with retrolingual level obstruction and that there is a greater change
      in tongue position. Acoustic analysis of snoring is a non-invasive diagnostic
      technique that can be easily applied at a relatively low cost. The analysis of
      formant frequencies will be a useful screening test for the prediction of
      occlusion sites. Moreover, smartphone can be effective for recording snoring
      sounds.

PMID- 27709293
TI  - Expression of Fas, FasL, caspase-8 and other factors of the extrinsic apoptotic
      pathway during the onset of interdigital tissue elimination.
AB  - Elimination of the interdigital web is considered to be the classical model for
      assessing apoptosis. So far, most of the molecules described in the process have
      been connected to the intrinsic (mitochondrial) pathway. The extrinsic (receptor
      mediated) apoptotic pathway has been rather neglected, although it is important
      in development, immunomodulation and cancer therapy. This work aimed to
      investigate factors of the extrinsic apoptotic machinery during interdigital
      regression with a focus on three crucial initiators: Fas, Fas ligand and caspase
      8. Immunofluorescent analysis of mouse forelimb histological sections revealed
      abundant expression of these molecules prior to digit separation. Subsequent PCR
      Array analyses indicated the expression of several markers engaged in the
      extrinsic pathway. Between embryonic days 11 and 13, statistically significant
      increases in the expression of Fas and caspase-8 were observed, along with other
      molecules involved in the extrinsic apoptotic pathway such as Dapk1, Traf3,
      Tnsf12, Tnfrsf1A and Ripk1. These results demonstrate for the first time the
      presence of extrinsic apoptotic components in mouse limb development and indicate
      novel candidates in the molecular network accompanying the regression of
      interdigital tissue during digitalisation.

PMID- 27709294
TI  - Amputated limb by cerclage wire of femoral diaphyseal fracture: a case report.
AB  - An entrapment of the femoral artery by cerclage wiring is a rare complication
      after spiral diaphyseal femoral fractures. We report the case of an 82-year-old
      female treated by an antegrade intramedullary nailing and multiple cable
      augmentation, which was then complicated by injury to the femoral artery that
      resulted in ipsilateral leg necrosis and amputation. The entrapment was caused by
      direct belting by the cable and resulted in a total obstruction of the femoral
      artery.

PMID- 27709295
TI  - Topically applied manganese-porphyrins BMX-001 and BMX-010 display a significant
      anti-inflammatory response in a mouse model of allergic dermatitis.
AB  - In this study, we topically administered two antioxidant compounds, the manganese
      porphyrin-derivatives BMX-001 and BMX-010, in a mouse model of allergic
      dermatitis and compared the efficacy for reduction of itch and inflammation. In
      vitro effects of BMX-001 and BMX-010 on keratinocytes, bone marrow derived
      dendritic cells (BMDCs) and T-cells were initially analysed. For assessment of
      scratching behaviour, BMX-001 and BMX-010 (0.01 and 0.1 %) were topically applied
      16 h and/or 1 h before compound 48/80 or toluene-2,4,-diisocyanate (TDI)
      challenge in a TDI induced mouse dermatitis model. Additionally, assessment of
      allergic skin inflammation was performed in a similar manner in the TDI model.
      Post-treatment ear thickness was measured 24 h after TDI challenge and compared
      to basal values. The mice were sacrificed and the ear auricle was removed for
      further analysis. In vitro, both BMX substances significantly inhibited cytokine
      production of keratinocytes as well as of BMDC and T-cell proliferation. Topical
      treatment with BMX cream resulted in a significant decrease in scratching
      behaviour in the compound 48/80 model, but not in the TDI model. Mice treated
      with BMX-001 and BMX-010 showed a moderate dose dependent decrease in ear
      thickness, and interestingly, the concentration of the cytokines IL-1beta and IL
      4 in inflamed skin was reduced by 80-90 % by all treatment options. These first
      results suggest the potential benefit of a BMX-001 and BMX-010 cream for the
      treatment of allergic-inflammatory skin diseases.

PMID- 27709296
TI  - Validity of a perceptually-regulated step test protocol for assessing
      cardiorespiratory fitness in healthy adults.
AB  - PURPOSE: To determine whether maximal oxygen uptake (VO2max) could be predicted
      accurately and reliably from a 2-step, perceptually-regulated exercise test
      (PRET) in healthy adults. METHODS: Sixteen participants (31.7 +/- 11.3 years, 3
      females) completed three PRETs (separated by 24-72 h) and one maximal,
      perceptually-regulated, graded exercise test (PRETmax) on a motorized treadmill.
      Oxygen uptake (VO2) and heart rate (HR) were recorded during each test. VO2
      values for RPE range 9-15 were extrapolated to RPE 20 and age-predicted maximal
      HR (HRmax) using individual linear regression analysis to predict VO2max values
      compared to measured VO2max. RESULTS: VO2 and HR values were consistent between
      each of four RPE levels of the PRET. ICC values ranged between 0.76 and 0.85.
      Predicted VO2max from both methods were lower than measured VO2max (p < 0.01).
      Limits of agreement (LoA) for measured (41.4 +/- 5.3 ml kg-1 min-1) versus
      predicted VO2max from each of the three PRETs using RPE20 were -1.2 +/- 15.6, 
      1.0 +/- 7.2 and -2.1 +/- 5.5 and for HRmax were -1.8 +/- 4.2; -2.6 +/- 4.2 and 
      2.4 +/- 4.4 ml kg-1 min-1 for PRET 1, 2 and 3, respectively. CONCLUSIONS: The
      step PRET elicited significant and reliable increases in VO2 across the four RPE
      levels, but under-estimated treadmill VO2max. However, there was better agreement
      between measured and predicted VO2max when extrapolated to HRmax. As evidence
      indicates the underestimation of VO2max is explained by the difference in the
      mode of exercise, the step PRET provides a simple and convenient test of
      cardiorespiratory fitness.

PMID- 27709297
TI  - Silicate calculi, a rare cause of kidney stones in children.
AB  - BACKGROUND: Urinary silicate calculi in humans are extremely rare. Reported cases
      of silicate calculi are mostly documented in adults and are commonly related to
      an excessive intake of magnesium trisilicate in food or drugs. Published studies
      on the presence of silicate calculi in children are scarce. CASES: Three cases of
      silicate kidney stones without prior silicate intake are reported. Two patients
      underwent surgical treatment, and the third patient was treated using
      conservative methods. Urinalysis revealed no underlying metabolic abnormalities.
      Analyses revealed that silicate was the major component of the stones.
      CONCLUSION: Siliceous deposits in urinary stones may be more common than
      anticipated, and the underlying pathophysiology remains to be clarified.

PMID- 27709298
TI  - Removal of extracellular coat from giant sperm in female receptacle induces sperm
      motility in Mytilocypris mytiloides (Cyprididae, Ostracoda, Crustacea).
AB  - Previous studies of cypridoidean ostracods have noted that (1) their giant
      spermatozoa are immotile inside the male, (2) these spermatozoa are motile in the
      female seminal receptacle and (3) these receptacles are often filled with empty
      sperm coats. Such findings have led previous authors to hypothesize that sperm
      must shed their coats in the female receptacle to become motile. We present light
      and electron microscopy results and video recordings of mating experiments with
      virgin specimens of Mytilocypris mytiloides. We show that the empty sperm coats
      frequently found in the female receptacles are not the result of sperm molting
      but are the resistant inner coats of exhausted sperm not used for egg
      fertilization. In contrast, we show that an outer granular coating material is
      successively removed from the sperm while resident inside the female receptacles
      before first oviposition occurs. During this period, previously immotile sperm
      gain motility, showing strong movement shortly before first oviposition takes
      place. By correlation of these phenomena, we suggest that dissolution of the
      outer coat material is required for motility to develop.

PMID- 27709299
TI  - A practical guide for the identification of major sulcogyral structures of the
      human cortex.
AB  - The precise sulcogyral localization of cortical lesions is mandatory to improve
      communication between practitioners and to predict and prevent post-operative
      deficits. This process, which assumes a good knowledge of the cortex anatomy and
      a systematic analysis of images, is, nevertheless, sometimes neglected in the
      neurological and neurosurgical training. This didactic paper proposes a brief
      overview of the sulcogyral anatomy, using conventional MR-slices, and also
      reconstructions of the cortical surface after a more or less extended inflation
      process. This method simplifies the cortical anatomy by removing part of the
      cortical complexity induced by the folding process, and makes it more
      understandable. We then reviewed several methods for localizing cortical
      structures, and proposed a three-step identification: after localizing the
      lateral, medial or ventro-basal aspect of the hemisphere (step 1), the main
      interlobar sulci were located to limit the lobes (step 2). Finally, intralobar
      sulci and gyri were identified (step 3) thanks to the same set of rules. This
      paper does not propose any new identification method but should be regarded as a
      set of practical guidelines, useful in daily clinical practice, for detecting the
      main sulci and gyri of the human cortex.

PMID- 27709300
TI  - Methamphetamine self-administration modulates glutamate neurophysiology.
AB  - World-wide methamphetamine (meth) use is increasing at a rapid rate; therefore,
      it has become increasingly important to understand the synaptic changes and
      neural mechanisms affected by drug exposure. In rodents, 6-h access to contingent
      meth results in an escalation of drug intake and impaired cognitive sequelae
      typically associated with changes within the corticostriatal circuitry. There is
      a dearth of knowledge regarding the underlying physiological changes within this
      circuit following meth self-administration. We assessed pre- and postsynaptic
      changes in glutamate transmission in the medial prefrontal cortex (mPFC) and
      nucleus accumbens (NAc) following daily 6-h meth self-administration. In the
      mPFC, meth caused postsynaptic adaptations in ionotropic glutamate receptor
      distribution and function, expressed as a decrease in AMPA/NMDA ratio. This
      change was driven by an increase in NMDA receptor currents and an increase in
      GluN2B surface expression. In the NAc, meth decreased the paired-pulse ratio and
      increased the frequency of spontaneous excitatory postsynaptic currents with no
      indication of postsynaptic changes. These changes in mPFC synapses and NAc
      activity begin to characterize the impact of meth on the corticostriatal
      circuitry.

PMID- 27709301
TI  - [Establish a prognosis for elderly patients after TAVR using coagulation
      analysis?]

PMID- 27709302
TI  - Cerebellar vermis: a vulnerable location of remote brain haemorrhages after
      thrombolysis for ischaemic stroke.
AB  - Extra-ischaemic (remote) brain heamorrhages after thrombolysis for ischaemic
      stroke occur in less than 3 % of treated patients, but it worsens prognosis.
      Little attention has been paid to the location of the haematomas. Among 12
      patients with remote brain haemorrhage after thrombolysis, we report three
      patients with haemorrhage in the cerebellar vermis (25 %), with poor outcome.
      Previous hypertensive vasculopathy is deemed to be the most plausible cause.

PMID- 27709304
TI  - Differences in the phenotypic effects of mutations in homologous MrpA and MrpD
      subunits of the multi-subunit Mrp-type Na+/H+ antiporter.
AB  - Mrp antiporters are the sole antiporters in the Cation/Proton Antiporter 3 family
      of transporter databases because of their unusual structural complexity, 6-7
      hydrophobic proteins that function as a hetero-oligomeric complex. The two
      largest and homologous subunits, MrpA and MrpD, are essential for antiport
      activity and have direct roles in ion transport. They also show striking homology
      with proton-conducting, membrane-embedded Nuo subunits of respiratory chain
      complex I of bacteria, e.g., Escherichia coli. MrpA has the closest homology to
      the complex I NuoL subunit and MrpD has the closest homology to the complex I
      NuoM and N subunits. Here, introduction of mutations in MrpD, in residues that
      are also present in MrpA, led to defects in antiport function and/or complex
      formation. No significant phenotypes were detected in strains with mutations in
      corresponding residues of MrpA, but site-directed changes in the C-terminal
      region of MrpA had profound effects, showing that the MrpA C-terminal region has
      indispensable roles in antiport function. The results are consistent with a
      divergence in adaptations that support the roles of MrpA and MrpD in secondary
      antiport, as compared to later adaptations supporting homologs in primary proton
      pumping by the respiratory chain complex I.

PMID- 27709303
TI  - Antarctic strict anaerobic microbiota from Deschampsia antarctica vascular plants
      rhizosphere reveals high ecology and biotechnology relevance.
AB  - The Antarctic soil microbial community has a crucial role in the growth and
      stabilization of higher organisms, such as vascular plants. Analysis of the soil
      microbiota composition in that extreme environmental condition is crucial to
      understand the ecological importance and biotechnological potential. We evaluated
      the efficiency of isolation and abundance of strict anaerobes in the vascular
      plant Deschampsia antarctica rhizosphere collected in the Antarctic's Admiralty
      Bay and associated biodiversity to metabolic perspective and enzymatic activity.
      Using anaerobic cultivation methods, we identified and isolated a range of
      microbial taxa whose abundance was associated with Plant Growth-Promoting
      Bacteria (PGPB) and presences were exclusively endemic to the Antarctic
      continent. Firmicutes was the most abundant phylum (73 %), with the genus
      Clostridium found as the most isolated taxa. Here, we describe two soil
      treatments (oxygen gradient and heat shock) and 27 physicochemical culture
      conditions were able to increase the diversity of anaerobic bacteria isolates.
      Heat shock treatment allowed to isolate a high percentage of new species (63.63
      %), as well as isolation of species with high enzymatic activity (80.77 %), which
      would have potential industry application. Our findings contribute to the
      understanding of the role of anaerobic microbes regarding ecology, evolutionary,
      and biotechnological features essential to the Antarctic ecosystem.

PMID- 27709305
TI  - Analysis of the safety evaluation for premarketing clinical trials of
      hemodialyzer and of postmarketing safety reports of hemodialyzer in Japan and the
      US: insights into the construction of a sophisticated premarketing evaluation.
AB  - Our aim was to conduct a scoping review of the regulations for hemodialyzers in
      the safety evaluation in Japan and the United States, and to evaluate the
      criteria for premarketing clinical trials and postmarketing safety reports to
      inform the development of a sophisticated premarketing evaluation in Japan.
      Regulations for approval of hemodialyzers were identified from the databases of
      the Ministry of Health, Labor and Welfare in Japan and the Federal Drug Agency
      (FDA) in the United States (US). The criteria for premarket clinical trials and
      postmarketing safety reports were evaluated for both countries. Standards in
      Japan required evaluation of blood compatibility and reporting of acute adverse
      effects by a premarketing clinical trial in 6 of 86 applications with
      semipermeable membrane materials deemed to be different to those of previously
      approved devices from 1983 to 31 August 2015. By comparison, the clinical trial
      was required in one of 545 approvals in the US from 1976 to 29 January 2016, but
      blood compatibility was not the point. All postmarketing adverse effects
      identified in Japan were included in the set of 'warnings'. The more stringent
      requirements for evaluation of blood compatibility and acute adverse effects in
      Japan seemed to be related to differences in the history of quality management
      systems for medical devices between the two countries. This study revealed that
      there were differences between Japan and the US in requiring the premarketing
      clinical trials for the hemodialyzers. Our findings could be useful for
      constructing sophisticated premarketing safety evaluation.

PMID- 27709306
TI  - Axillo-iliac arteriovenous hemodialysis graft creation with an early cannulation
      device.
AB  - Exhaustion of superficial veins coupled with the presence of intrathoracic
      central venous occlusions remains a significant obstacle for hemodialysis access
      creation; complex arteriovenous graft (AVG) configurations have been described.
      The axillary-iliac AVG was first reported in 1987, and few authors have explored
      this access. We evaluated our experience with this AVG configuration utilizing
      the early cannulation (EC) graft FlixeneTM (Atrium TM, Hudson, NH, USA). Eight
      patients (75 % men; mean age 37 +/- 10 years) with End-Stage Renal Disease (ESRD)
      underwent axillo-iliac AVG creation with FlixeneTM grafts; all had exhausted
      peripheral veins, occluded thoracic central veins, and inadequate femoral veins.
      Inflow from the axillary artery and outflow in iliocaval system was assessed
      prior to access creation. An axillary-to-common iliac AVG was constructed using a
      6 mm (mm) EC graft and tunneled in the chest and abdominal wall. Eight grafts
      were implanted; all were patent after placement. Seven (88 %) were successfully
      used for hemodialysis within 72 h and one (12 %) within 96. During the mean
      follow-up of 6 months, 5 (62 %) patients underwent thrombectomy, 1 (12 %) of them
      had balloon angioplasty at the vein anastomosis, and 2 (25 %) grafts were removed
      secondary to infection. The remaining grafts are still functioning. Complications
      as high-output heart failure, steal syndrome and venous hypertension were not
      observed. Construction of axillo-iliac AVG with EC grafts in the setting of
      exhausted veins, occluded intrathoracic central veins and hostile groins, is a
      viable arteriovenous access alternative while avoiding central venous catheters.

PMID- 27709307
TI  - Validation of a predictive model for identifying febrile young infants with
      altered urinalysis at low risk of invasive bacterial infection.
AB  - In 2015, a predictive model for invasive bacterial infection (IBI) in febrile
      young infants with altered urine dipstick was published. The aim of this study
      was to externally validate a previously published set of low risk criteria for
      invasive bacterial infection in febrile young infants with altered urine
      dipstick. Retrospective multicenter study including nine Spanish hospitals.
      Febrile infants <=90 days old with altered urinalysis (presence of leukocyturia
      and/or nitrituria) were included. According to our predictive model, an infant is
      classified as low-risk for IBI when meeting all the following: appearing well at
      arrival to the emergency department, being >21 days old, having a procalcitonin
      value <0.5 ng/mL and a C-reactive protein value <20 mg/L. IBI was considered as
      secondary to urinary tract infection if the same pathogen was isolated in the
      urine culture and in the blood or cerebrospinal fluid culture. A total of 391
      patients with altered urine dipstick were included. Thirty (7.7 %) of them
      developed an IBI, with 26 (86.7 %) of them secondary to UTI. Prevalence of IBI
      was 2/104 (1.9 %; CI 95% 0.5-6.7) among low-risk patients vs 28/287 (9.7 %; CI
      95% 6.8-13.7) among high-risk patients (p < 0.05). Sensitivity of the model was
      93.3 % (CI 95% 78.7-98.2) and negative predictive value was 98.1 % (93.3-99.4).
      Although our predictive model was shown to be less accurate in the validation
      cohort, it still showed a good discriminatory ability to detect IBI. Larger
      prospective external validation studies, taking into account fever duration as
      well as the role of ED observation, should be undertaken before its
      implementation into clinical practice.

PMID- 27709308
TI  - Evaluation of the improvement effect of laser acupuncture biostimulation in
      asthmatic children by exhaled inflammatory biomarker level of nitric oxide.
AB  - Variable therapy of asthma is not sufficient yet to achieve good asthma control.
      Therapy decision requires serial investigations. Low-level laser acupuncture is a
      suitable non-invasive modality of complementary medicine. The exhaled breath
      condensate (EBC) is easy and useful to evaluate the efficacy of drugs or novel
      therapy. This study aimed to evaluate the effectiveness of low-level laser
      biostimulation of acupuncture points on asthma improvement in children. Forty
      eight asthmatic children were subdivided into case (laser) group, which received
      12 direct contact low-power laser acupuncture sessions (three sessions/week) on
      specific traditional Chinese acupuncture points for bronchial asthma, and control
      asthmatic group, which received sham laser acupuncture on the same acupoints and
      number of sessions of the case (laser) group. Low-power Multichannel Aculas-AM
      laser (grade II) of wave length 780 nm, output power 800 mw, and beam spot size
      0.1 cm2 with continuous mode was used. Eighteen acupoints were stimulated for 2
      min, giving energy of 9.6 J/cm2/acupoint. The total session time was 3 min. Both
      groups were evaluated pre- and post-laser acupuncture intervention by recording
      levels of asthma control, pulmonary function, and EBC nitric oxide. In the case
      (laser) group, 91.7 % of patients experienced an improvement in the level of
      asthma control versus 25 % in the control group (p < 0.001). This was associated
      with a significant decrease of the breath condensate FENO concentration (p <
      0.001) and significant increase of spirometry parameters (p < 0.001) in the case
      (laser) group. Application of laser acupuncture treatment given with conventional
      therapy can effectively improve bronchial asthma more than prescription of
      medications alone could.

PMID- 27709310
TI  - Survey of Pathogenic Chytrid Fungi (Batrachochytrium dendrobatidis and B.
      salamandrivorans) in Salamanders from Three Mountain Ranges in Europe and the
      Americas.
AB  - Batrachochytrium salamandrivorans (Bsal) is a virulent fungal pathogen that
      infects salamanders. It is implicated in the recent collapse of several
      populations of fire salamanders in Europe. This pathogen seems much like that of
      its sister species, Batrachochytrium dendrobatidis (Bd), the agent responsible
      for anuran extinctions and extirpations worldwide, and is considered to be an
      emerging global threat to salamander communities. Bsal thrives at temperatures
      found in many mountainous regions rich in salamander species; because of this, we
      have screened specimens of salamanders representing 17 species inhabiting
      mountain ranges in three continents: The Smoky Mountains, the Swiss Alps, and the
      Peruvian Andes. We screened 509 salamanders, with 192 representing New World
      salamanders that were never tested for Bsal previously. Bsal was not detected,
      and Bd was mostly present at low prevalence except for one site in the Andes.

PMID- 27709309
TI  - Suitable Concentrations of Uric Acid Can Reduce Cell Death in Models of OGD and
      Cerebral Ischemia-Reperfusion Injury.
AB  - Cerebral infarction (CI) is a common clinical cerebrovascular disease, and to
      explore the pathophysiological mechanisms and seek effective treatment means are
      the hotspot and difficult point in medical research nowadays. Numerous studies
      have confirmed that uric acid plays an important role in CI, but the mechanism
      has not yet been clarified. When treating HT22 and BV-2 cells with different
      concentrations of uric acid, uric acid below 450 MUM does not have significant
      effect on cell viability, but uric acid more than 500 MUM can significantly
      inhibit cell viability. After establishing models of OGD (oxygen-glucose
      deprivation) with HT22 and BV-2 cells, uric acid at a low concentration (50 MUM)
      cannot improve cell viability and apoptosis, and Reactive oxygen species (ROS)
      levels during OGD/reoxygenation; a suitable concentration (300 MUM) of uric acid
      can significantly improve cell viability and apoptosis, and reduce ROS production
      during OGD/reoxygenation; but a high concentration (1000 MUM) of uric acid can
      further reduce cell viability and enhance ROS production. After establishing
      middle cerebral artery occlusion of male rats with suture method, damage and
      increase of ROS production in brain tissue could be seen, and after adding
      suitable concentration of uric acid, the degree of brain damage and ROS
      production was reduced. Therefore, different concentrations of uric acid should
      have different effect, and suitable concentrations of uric acid have
      neuroprotective effect, and this finding may provide guidance for study on the
      clinical curative effect of uric acid.

PMID- 27709311
TI  - Transmission Dynamics of the West Nile Virus in Mosquito Vector Populations under
      the Influence of Weather Factors in the Danube Delta, Romania.
AB  - Mosquitoes were collected in the Danube Delta during the active seasons of 2011
      2013. For Culex spp. mosquitoes, the abundance was calculated. Culex pipiens
      (sensu lato), (s.l.) and Culex modestus pools were tested for the presence of
      West Nile virus (WNV) genome, and the maximum likelihood of the infection rate
      was established. Mean daily temperatures and precipitation were obtained for the
      closest meteorological station. A negative binominal model was used to evaluate
      linkages between the temperature/precipitation and mosquito population size. A
      zero-inflated negative binomial model was used to test the relationship between
      the temperature and the infection rate. A single complex model for infection rate
      prediction was also used. The linkages were calculated for lag 0 and for 10 days
      earlier (lag 1), 20 days earlier (lag 2), and 30 days earlier (lag 3).
      Significant positive linkages (P < 0.001) were detected between temperature and
      mosquito population size for lag 1, lag 2, and lag 3. The linkages between
      temperature and infection rates were positive and significant for lag 2 and lag
      3. Negative significant (P < 0.001) results were detected between precipitation
      and infection rates for lags 1, 2, and 3. The complex model showed that the best
      predictors for infection rate are the temperature, 20 days earlier (positive
      linkage) and the precipitation, 30 days earlier (negative linkage). Positive
      temperature anomalies in spring and summer and rainfall decrease contributed to
      the increase in the Culex spp. abundance and accelerated the WNV amplification in
      mosquito vector populations in the following weeks.

PMID- 27709312
TI  - Pathways between physical activity and quality of life in African-American breast
      cancer survivors.
AB  - INTRODUCTION: Several studies have indicated that the relationship between
      physical activity and quality of life is not directed but mediated through
      various pathways. The purpose of this study was to assess the role of cancer
      related fatigue, disability, and functional status as potential mediators in
      African-American breast cancer survivors. METHODS: African-American breast cancer
      survivors (N = 135, mean age = 63) aged 55 years and older participated in a web
      based survey consisting of measures assessing physical activity, functional
      status, cancer-related fatigue, disability, quality of life, and sociodemographic
      and medical characteristics. Structural equation modeling was used to assess the
      structural relationships among the constructs. RESULTS: The initial structural
      model fit the data and revealed a significant relationship between physical
      activity and quality of life (beta = 0.34, P < 0.01). Subsequent structural
      models with proposed complementary and mediating paths of fatigue, function, and
      disability fit the data. The adjusted model indicated that physical activity was
      no longer associated with quality of life (beta = 0.11, P > 0.05) and mediated
      through pathways of functional status and fatigue (total beta = 0.16, P < 0.01).
      The final adjusted model accounted for 32 % of the variance in quality of life.
      CONCLUSION: Our data suggest that physical activity may be indirectly related to
      quality of life through pathways consisting of fatigue and functional status.
      Further longitudinal studies are needed to test the pathways through which
      varying levels of physical activity influence cancer-related and quality of life
      outcomes in minority cancer survivors.

PMID- 27709313
TI  - A randomized, multi-center, open-label, phase III study of once-per-cycle DA
      3031, a pegylated G-CSF, in comparison with daily filgrastim in patients
      receiving TAC chemotherapy for breast cancer.
AB  - PURPOSE: This multi-center, randomized, phase III study was conducted to
      demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in
      patients during the first cycle of chemotherapy for breast cancer in terms of the
      duration of severe neutropenia (DSN). METHODS: Seventy-four patients with breast
      cancer who were receiving combination chemotherapy with docetaxel, doxorubicin,
      and cyclophosphamide (TAC) were enrolled. All participants were randomized to
      receive either daily subcutaneous injections of filgrastim 100 MUg/m2/day for up
      to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg
      on day 2 of each chemotherapy cycle. RESULTS: The mean duration of grade 4 (G4)
      neutropenia in cycle 1 was 2.08 +/- 0.85 days for the filgrastim group and 2.28
      +/- 1.14 days for the DA-3031 group. The difference between groups was 0.2 +/-
      1.10 days (95 % confidence interval (CI) = -0.26, 0.66), which supported non
      inferiority. No statistically significant differences were observed in nadir
      absolute neutrophil count (ANC) (154.34/mm3 and 161.75/mm3 for the filgrastim and
      DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 +/-
      0.75 and 9.83 +/- 1.56 days in the filgrastim and DA-3031 groups, respectively; P
      = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving
      filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was
      determined to be related to the study drug. CONCLUSIONS: DA-3031 and daily
      filgrastim are similar in regard to DSN and safety in breast cancer patients
      receiving TAC chemotherapy.

PMID- 27709314
TI  - A simple and robust protocol for high-yield expression of perdeuterated proteins
      in Escherichia coli grown in shaker flasks.
AB  - We present a simple, convenient and robust protocol for expressing perdeuterated
      proteins in E. coli BL21(DE3) cells in shaker flasks that reduces D2O usage
      tenfold and d7-glucose usage by 30 %. Using a modified M9 medium and optimized
      growth conditions, we were able to grow cells in linear log phase to an OD600 of
      up to 10. Inducing the cells with isopropyl beta-D-1-thiogalactopyranoside at an
      OD600 of 10, instead of less than 1, enabled us to increase the cell mass tenfold
      per unit volume of cell culture. We show that protein expression levels per cell
      are the same when induced at an OD600 between 1 and 10 under these growth
      conditions. Thus, our new protocol can increase protein yield per unit volume of
      cell culture tenfold. Adaptation of E. coli from H2O-based to D2O-based medium is
      also key for ensuring high levels of protein expression in D2O. We find that a
      simple three-step adaptation approach-Luria-Bertani (LB) medium in H2O to LB in
      D2O to modified-M9 medium in D2O is both simple and reliable. The method
      increases the yield of perdeuterated proteins by up to tenfold using commonly
      available air shakers without any requirement for specialized fermentation
      equipment.

PMID- 27709315
TI  - Inhibition of IRF8 Negatively Regulates Macrophage Function and Impairs Cutaneous
      Wound Healing.
AB  - The inflammatory response is essential for normal cutaneous wound healing.
      Macrophages, as critical inflammatory cells, coordinate inflammation and
      angiogenesis phases during wound healing. It has been reported that the
      transcription factor interferon regulatory factor 8 (IRF8), a member of the IRF
      family, plays a critical role in the development and function of macrophages and
      is associated with inflammation. However, the role of IRF8 in cutaneous wound
      healing and its underlying mechanism remain elusive. Through immunohistochemical
      (IHC) staining, we showed that IRF8 is involved in the wound repair process in
      mice and patients. Furthermore, we ascertain that the repression of IRF8 by small
      interfering RNA (siRNA) leads to delayed wound healing. To explore the mechanism
      by which IRF8 impacts wound healing, we observed its effect on macrophage-related
      mediators by IHC or real-time PCR. The results demonstrated that the inhibition
      of IRF8 decreases the mRNA expression of inflammatory mediators associated with
      M1 macrophage (il-1b, il-6, inos, and tnf-a) but no impact on M2 macrophage
      related mediators (arg-1, mrc-1, and il-10) and the number of macrophages in the
      wounds. Furthermore, the inhibition of IRF8 induced apoptosis in the wounds. In
      summary, this study demonstrates that the down-regulation of IRF8 in the wound
      leads to impaired wound healing possibly through the regulation of macrophage
      function and apoptosis in skin wound.

PMID- 27709316
TI  - Coumestrol Counteracts Interleukin-1beta-Induced Catabolic Effects by Suppressing
      Inflammation in Primary Rat Chondrocytes.
AB  - In the present study, we investigated the anti-catabolic effects of coumestrol, a
      phytoestrogen derived from herbal plants, against interleukin-1beta-induced
      cartilage degeneration in primary rat chondrocytes and articular cartilage.
      Coumestrol did not affect the viability of human normal oral keratinocytes and
      primary rat chondrocytes treated for 24 h and 21 days, respectively. Although
      coumestrol did not significantly increase the proteoglycan contents in long-term
      culture, it abolished the interleukin-1beta-induced loss of proteoglycans in
      primary rat chondrocytes and knee articular cartilage. Furthermore, coumestrol
      suppressed the expression of matrix-degrading enzymes such as matrix
      metalloproteinase-13, -3, and -1 in primary rat chondrocytes stimulated with
      interleukin-1beta. Moreover, the expression of catabolic factors such as nitric
      oxide synthase, cyclooxygenase-2, prostaglandin E2, and inflammatory cytokines in
      interleukin-1beta-stimulated primary rat chondrocytes was suppressed by
      coumestrol. In summary, these results indicate that coumestrol counteracts the
      catabolic effects induced by interleukin-1beta through the suppression of
      inflammation. Therefore, based on its biological activity and safety profile,
      coumestrol could be used as a potential anti-catabolic biomaterial for
      osteoarthritis.

PMID- 27709317
TI  - Docking-undocking combination applied to the D3R Grand Challenge 2015.
AB  - Novel methods for drug discovery are constantly under development and independent
      exercises to test and validate them for different goals are extremely useful. The
      drug discovery data resource (D3R) Grand Challenge 2015 offers an excellent
      opportunity as an external assessment and validation experiment for Computer
      Aided Drug Discovery methods. The challenge comprises two protein targets and
      prediction tests: binding mode and ligand ranking. We have faced both of them
      with the same strategy: pharmacophore-guided docking followed by dynamic
      undocking (a new method tested experimentally here) and, where possible, critical
      assessment of the results based on pre-existing information. In spite of using
      methods that are qualitative in nature, our results for binding mode and ligand
      ranking were amongst the best on Hsp90. Results for MAP4K4 were less positive and
      we track the different performance across systems to the level of previous
      knowledge about accessible conformational states. We conclude that docking is
      quite effective if supplemented by dynamic undocking and empirical information
      (e.g. binding hot spots, productive protein conformations). This setup is well
      suited for virtual screening, a frequent application that was not explicitly
      tested in this edition of the D3R Grand Challenge 2015. Protein flexibility
      remains as the main cause for hard failures.

PMID- 27709318
TI  - Self-Assembly of Colloidal Photonic Crystals of PS@PNIPAM Nanoparticles and
      Temperature-Responsive Tunable Fluorescence.
AB  - A strategy for significantly enhancing fluorescence is developed based on the
      coupling of optical properties of colloidal photonic crystals (CPCs) with
      responsive microgel. In this paper, thermoresponsive microgel PNIPAM was employed
      for the fabrication of core-shell structure. The core-shell PS@PNIPAM
      nanoparticles (NPs) are then assembled to CPCs by a vertical deposition method.
      Subsequently, the novel functional material (RhB/CPCs) can be prepared by
      depositing fluorescent dye molecules (RhB) on the top of PS@PNIPAM CPCs. We
      obtained an increase in the fluorescent intensity up to 15-fold and 22-fold
      compared with RhB on the glass slid and the uneven film. Due to the unique
      responsive shrinking properties of PNIPAM shell, the amplifying fluorescence
      behavior of CPCs can be well tuned by varying the temperature. In contrast to RhB
      on the glass slid, a 15-fold and 12-fold fluorescence enhancement can be observed
      when the temperature of RhB/CPCs was 20  degrees C and 50  degrees C,
      respectively. The mechanism on enhancement fluorescence of tunable CPCs can be
      achieved by measurements of thermoresponsive properties. The results indicate
      that the responsive fluorescence-amplifying method based on CPCs made with
      responsive core-shell NPs has a potential application for the development of
      efficient fluorescence sensors.

PMID- 27709319
TI  - Evaluation of HeartSmarts, a Faith-Based Cardiovascular Health Education Program.
AB  - In order to effectively address cardiovascular disease among African Americans,
      evidence-based health information must be disseminated within a context aligned
      with the values and beliefs of the population. Faith-based organizations play a
      critical role in meeting the religious and spiritual needs of many African
      Americans. Additionally, faith-based organizations can be effective in health
      promotion. A manual was created by incorporating biblical scriptures relating to
      health messages drawn from existing health manuals oriented toward African
      Americans. Lay health educators active in their churches participated in a 12
      week training to learn the basics of cardiovascular disease and methods for
      delivering the program to their congregations' members. After the completion of
      the training, these lay health educators recruited participants from their
      respective churches and administered their own 12-week HeartSmarts program.
      Measurements of participants' systolic and diastolic blood pressure (mmHg),
      height (in.), weight (lbs.), and waist circumference (in.) were taken, and
      cardiovascular disease knowledge assessments (based on 20 open-ended questions)
      were administered at the start and end of the 12-week programs. Fourteen
      predominantly African American churches in NYC participated. Of the 221
      participants, 199 completed the program. There were significant reductions in
      pretest and posttest total participant averages for systolic BP (4.48 mmHg, p <
      0.001), diastolic BP (3.38 mmHg, p < 0.001), weight (3lbs., p = 0.001), and BMI
      (0.46, p = 0.001). Cardiovascular disease health assessment scores had an average
      increase of 12.74 correct responses (p < 0.001). The HeartSmarts program may be
      an effective ecumenical and cultural model for disseminating health messages and
      reducing cardiovascular risk among African Americans.

PMID- 27709320
TI  - ZmDof3, a maize endosperm-specific Dof protein gene, regulates starch
      accumulation and aleurone development in maize endosperm.
AB  - KEY MESSAGE: To explore the function of Dof transcription factors during kernel
      development in maize, we first identified Dof genes in the maize genome. We found
      that ZmDof3 was exclusively expressed in the endosperm of maize kernel and had
      the features of a Dof transcription factor. Suppression of ZmDof3 resulted in a
      defective kernel phenotype with reduced starch content and a partially patchy
      aleurone layer. The expression levels of starch synthesis-related genes and
      aleurone differentiation-associated genes were down-regulated in ZmDof3 knockdown
      kernels, indicating that ZmDof3 plays an important role in maize endosperm
      development. The maize endosperm, occupying a large proportion of the kernel,
      plays an important role in seed development and germination. Current knowledge
      regarding the regulation of endosperm development is limited. Dof proteins, a
      family of plant-specific transcription factors, play critical roles in diverse
      biological processes. In this study, an endosperm-specific Dof protein gene,
      ZmDof3, was identified in maize through genome-wide screening. Suppression of
      ZmDof3 resulted in a defective kernel phenotype. The endosperm of ZmDof3
      knockdown kernels was loosely packed with irregular starch granules observed by
      electronic microscope. Through genome-wide expression profiling, we found that
      down-regulated genes were enriched in GO terms related to carbohydrate
      metabolism. Moreover, ZmDof3 could bind to the Dof core element in the promoter
      of starch biosynthesis genes Du1 and Su2 in vitro and in vivo. In addition, the
      aleurone at local position in mature ZmDof3 knockdown kernels varied from one to
      three layers, which consisted of smaller and irregular cells. Further analyses
      showed that knockdown of ZmDof3 reduced the expression of Nkd1, which is involved
      in aleurone cell differentiation, and that ZmDof3 could bind to the Dof core
      element in the Nkd1 promoter. Our study reveals that ZmDof3 functions in maize
      endosperm development as a positive regulator in the signaling system controlling
      starch accumulation and aleurone development.

PMID- 27709321
TI  - Lignans from guaiac resin decrease nitric oxide production in interleukin 1beta
      treated hepatocytes.
AB  - Guaiac resin, extracted from the heartwood of Guaiacum officinale L. or G.
      sanctum L., is speculated to have anti-inflammatory effects. Lignans were
      purified from guaiac resin (also known as gum guaiacum) by monitoring the nitric
      oxide (NO) production in rat hepatocytes treated with an inflammatory cytokine
      interleukin-1beta (IL-1beta). Six lignans were purified from guaiac resin and
      identified as: dehydroguaiaretic acid (1), (+)-trans-1,2-dihydrodehydroguaiaretic
      acid (2), furoguaiaoxidin (3), meso-dihydroguaiaretic acid (4), furoguaiacin
      (i.e., alpha-guaiaconic acid) (5), and nectandrin B (6). To our knowledge, this
      is the first time that 1 has been isolated from guaiac resin as a non-derivative.
      Compounds 2 and 6 were first found in guaiac resin. Compound 3 was first isolated
      from a natural source as a non-derivative. Furthermore, 1-6 significantly
      suppressed NO production in IL-1beta-treated hepatocytes. Because anti
      inflammatory compounds suppress NO production, this system is often used to
      measure the anti-inflammatory effects of Kampo drugs and herbal constituents. The
      NO-suppressing activity of the six lignans isolated in this study indicates that
      guaiac resin has anti-inflammatory effects and that these lignans may be
      responsible for the anti-inflammatory effects of guaiac resin.

PMID- 27709322
TI  - Potential drug interactions with dietary and herbal supplements during
      hospitalization.
AB  - Dietary and herbal supplements (DHS) are widely used in the general population,
      including during hospitalization. Yet, their potential interactions with
      prescription drugs have seldom been delineated among inpatients. We aimed to
      evaluate potentially dangerous interactions of DHS with prescribed medications
      among inpatients. This was a cross-sectional prospective study involving a cohort
      of patients hospitalized in 12 departments of a public academic medical center
      (Bnai Zion Medical Center, Haifa, Israel) from 2009 to 2014. DHS users were
      determined via a questionnaire. The Natural Medicine database was used to search
      for potential DHS-drug interactions for identified DHS, and the clinical
      significance was evaluated using Lexi-interact online interaction analysis.
      Medical files were assessed for documentation of DHS use. Univariate and
      multivariate logistic regression analyses were used to characterize potential
      risk factors for DHS-drug interactions. Of 927 patients consenting to answer the
      questionnaire, 458 (49 %) reported DHS use. Of these, 215 (47 %) had at least one
      potential interaction during hospitalization (759 interactions). Of these
      interactions, 116 (15 %) were potentially clinically significant. Older age [OR =
      1.02 (1.01-1.04), p = 0.002], males [OR = 2.11 (1.35-3.29), p = 0.001] and
      increased number of used DHS [OR = 4.28 (2.28-8.03), p < 0.001] or drugs [OR =
      1.95 (1.17-3.26), p = 0.011] were associated with potential interactions in DHS
      users. Physicians documented only 16.5 % of DHS involved in these interactions in
      patients' medical files. In conclusion, a substantial number of inpatients use
      DHS with potential interactions with concomitant medications. Medical staff
      should be aware of this, question patients on DHS usage and check for such
      interactions.

PMID- 27709323
TI  - The isodense colloid cyst: an easily overlooked cause of intermittent acute
      obstructive hydrocephalus.

PMID- 27709324
TI  - Comparison of mid-term clinical outcomes between on-label and off-label use of
      rotational atherectomy.
AB  - While rotational atherectomy (RA) is used for complex lesions in percutaneous
      coronary intervention, there are several contraindications such as unprotected
      left main stenosis or left ventricular dysfunction. We previously reported that
      the incidence of in-hospital complications was significantly greater in off-label
      as compared to on-label use RA. However, the mid-term clinical outcomes between
      off-label and on-label RA have not been investigated. The purpose of this study
      was to compare the mid-term clinical outcomes between off-label (n = 156) and on
      label RA (n = 94). The primary endpoint was the incidence of major adverse
      cardiovascular events (MACE) defined as the composite of ischemia-driven target
      vessel revascularization (TVR), non-fatal MI, and all-cause death. We also
      identified 154 patients who underwent RA and follow-up angiography within 1 year,
      and compared quantitative coronary analysis between the off-label group (n = 96)
      and on-label group (n = 58). There was no significant difference in late luminal
      loss between the groups (0.03 +/- 0.53 mm in the off-label and -0.05 +/- 0.44 mm
      in the on-label groups, P = 0.57). However, the incidence of MACE was less in the
      on-label group (3.2 %) as compared to the off-label group (9.0 %) without
      reaching statistical significance (P = 0.08). In conclusion, mid-term clinical
      outcomes tended to be worse in the off-label group than in the on-label group. We
      may have to follow-up the patient who underwent off-label RA more carefully than
      the patient who underwent on-label RA.

PMID- 27709326
TI  - Blocking the flow of propionate into TCA cycle through a mutB knockout leads to a
      significant increase of erythromycin production by an industrial strain of
      Saccharopolyspora erythraea.
AB  - A high erythromycin producing mutant strain Saccharopolyspora erythraea HL3168 E3
      DeltamutB was constructed by deleting mutB (SACE_5639) gene encoding the beta
      subunit of methylmalonyl-CoA mutase of an industrial strain of S. erythraea
      HL3168 E3. Industrial media and process control strategies were adopted in a 5 L
      bioreactor for characterizing the physiological parameters. The total
      erythromycin titer and erythromycin A concentration in mutant were 46.9 (12740.5
      MUg/mL) and 64.9 % (8094.4 MUg/mL) higher than those in original strain,
      respectively, which were comparable to industrial erythromycin production. The
      specific glucose and n-propanol consumption rates were increased by 52.4 and 39.8
      %, respectively. During the rapid erythromycin synthesis phase, the yield of
      erythromycin on n-propanol also increased from 24.3 % in control group to 66.9 %
      in mutant group. Meanwhile, the specific formation rates of methylmalonyl-CoA and
      propionyl-CoA, two crucial precursors for erythromycin synthesis, were 1.89- and
      2.02-folds higher in the mutant strain, respectively.

PMID- 27709327
TI  - Erratum to: The effect of a performance-based intra-procedural checklist on a
      simulated emergency laparoscopic task in novice surgeons.

PMID- 27709325
TI  - Prediction of 1-year clinical outcomes using the SYNTAX score in patients with
      prior heart failure undergoing percutaneous coronary intervention: sub-analysis
      of the SHINANO registry.
AB  - Although coronary artery disease (CAD) is common in patients with heart failure
      (HF), little is known about the prognostic significance of coronary lesion
      complexity in patients with prior HF undergoing percutaneous coronary
      intervention (PCI). The aim of this study was to investigate whether the coronary
      Synergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery
      (SYNTAX) score could improve risk stratification in HF patients with CAD. Two
      hundred patients (mean age 73 +/- 11 years, left ventricular ejection fraction 49
      +/- 15 %) with prior HF who underwent PCI were divided into two groups stratified
      by SYNTAX score (median value 12) and tracked prospectively for 1 year. The study
      endpoint was the composite of major adverse cardiovascular events (MACE),
      including all-cause death, myocardial infarction, stroke, and hospitalization for
      worsening HF. Adverse events were observed in 39 patients (19.5 %). Patients with
      high SYNTAX scores (n = 100) showed worse prognoses than those with low scores (n
      = 100) (26.0 vs. 13.0 %, respectively, P = 0.021). In multivariate Cox-regression
      analysis, SYNTAX score >=12 was significantly associated with MACE (hazard ratio:
      1.99, 95 % confidence interval: 1.02-3.97; P = 0.045). In patients with prior HF
      and CAD, high SYNTAX scores predicted a high incidence of MACE. These results
      suggest that the SYNTAX score might be a useful parameter for improving risk
      stratification in these patients.

PMID- 27709328
TI  - Successful closure of defects in the upper gastrointestinal tract by endoscopic
      vacuum therapy (EVT): a prospective cohort study.
AB  - BACKGROUND: Perforations and anastomotic leakages of the upper gastrointestinal
      (GI) tract cause a high morbidity and mortality rate. Only limited data exist for
      endoscopic vacuum therapy (EVT) in the upper GI tract. METHODS: Fifty-two
      patients (37 men and 15 women, ages 41-94 years) were treated (12/2011-12/2015)
      with EVT for anastomotic insufficiency secondary to esophagectomy or gastrectomy
      (n = 39), iatrogenic esophageal perforation (n = 9) and Boerhaave syndrome (n =
      4). After diagnosis, polyurethane sponges were endoscopically positioned with a
      total of 390 interventions and continuous negative pressure of 125 mm of mercury
      (mmHg) was applied to the EVT-system. Sponges were changed endoscopically twice
      per week. Clinical and therapy-related data and mortality were analyzed. RESULTS:
      After 1-25 changes of the sponge at intervals of 3-5 days with a mean of 6 sponge
      changes and a mean duration of therapy of 22 days, the defects were healed in
      94.2 % of all patients without revision surgery. In three patients (6 %), EVT
      failed. Two of these patients died due to hemorrhage related to EVT. Four
      postinterventional strictures were observed during the follow-up of up to 4
      years. CONCLUSION: Esophageal wall defects of different etiology in the upper
      gastrointestinal tract can be treated successfully with EVT, considering that
      indication for EVT should be weighed carefully. EVT can be regarded as a novel
      life-saving therapeutic tool.

PMID- 27709329
TI  - Assessment of treatment options for rectosigmoid cancer: single-incision plus one
      port laparoscopic surgery, single-incision laparoscopic surgery, and conventional
      laparoscopic surgery.
AB  - BACKGROUND: The advantages of reduced-port laparoscopic surgery (RPLS) for
      rectosigmoid cancer treatment have been disputed. This study evaluated the
      outcomes of RPLS compared to conventional laparoscopic surgery (CLS) for
      rectosigmoid cancer. METHODS: Data from 211 patients who underwent a selective
      sigmoidectomy or anterior resection from August 2011 to June 2014 at a single
      institution were collected and analyzed via propensity score matching. Operative
      outcomes, inflammatory responses, pain intensity, oncologic outcomes, quality of
      life, and cosmetic results were compared between groups. RESULTS: After matching,
      96 patients (48 CLS and 48 RPLS) were evaluated. Sixteen RPLS cases underwent
      single-incision laparoscopic surgery (SILS), and 32 underwent single-incision
      plus one port laparoscopic surgery (SILS + 1). Baseline clinical characteristics
      were comparable between the RPLS and the CLS groups. Morbidity, pathologic
      outcomes, and 3-year disease-free survival and overall survival rates were also
      comparable between the 2 groups. Compared with the CLS group, the RPLS group had
      a shorter total incision length (p < 0.001); shorter time to liquid diet (p =
      0.027), ambulation (p = 0.026), and discharge (p < 0.001); and lower visual
      analogue scale scores during mobilization at postoperative days 3-5 (p < 0.05).
      The total operation times, C-reactive protein levels at 24 h and 96 h, and
      interleukin-6 levels at 24 h postoperatively were significantly lower in the SILS
      + 1 group than those in the CLS and SILS groups (p < 0.05). Compared with the CLS
      group, the RPLS group showed better social functioning at 6 months
      postoperatively (p = 0.011). The SILS and SILS + 1 groups showed similar cosmetic
      results, and both groups showed better results than the CLS group (p < 0.001).
      CONCLUSIONS: RPLS for rectosigmoid cancer is feasible, with short-term safety and
      long-term oncological safety comparable to that of CLS. Better cosmesis and
      accelerated recovery can be expected. SILS + 1 is a better choice than CLS or
      SILS for rectosigmoid cancer because it minimizes invasiveness and reduces
      technical difficulties.

PMID- 27709330
TI  - Microvascular Function in Aging Among Women Living with HIV.
AB  - Combined antiretroviral therapy (CART) has turned HIV-infection to a treatable
      chronic disease during which many patients survive to middle and older age.
      However, they prematurely develop non-AIDS comorbidities such as cardiovascular
      disease, metabolic syndrome, diabetes, and HIV-associated neurocognitive
      disorders (HAND). Microcirculatory changes and endothelial dysfunction occur
      early both in HIV-infected and in aging patients, in whom they usually precede
      cardiovascular and neurocognitive impairments. Also, mild cognitive involvement
      has been reported in women during the menopausal transition. Disruption of the
      blood-brain barrier, as well as microvascular and cerebral blood flow changes,
      has been reported in HIV patients with HAND, including postmenopausal women.
      However, most studies addressing this issue included women aged less than 50
      years. Whether HIV-infected women growing older with CART would be subsequently
      exposed to an increased progression of cognitive impairment overtime remains
      unknown.

PMID- 27709331
TI  - How to Diagnose and Treat Functional Chest Pain.
AB  - OPINION STATEMENT: Chest pain that is not explained by reflux disease or cardiac,
      musculoskeletal, mucosal, or motor esophageal abnormalities is classified as
      functional chest pain (FCP). Although several mechanisms are involved, esophageal
      hypersensitivity plays a major role and it could be considered a biomarker for
      FCP. Psychologic comorbidity such as anxiety, neuroticism, depression, and
      somatization is common. When the diagnosis of FCP is suspected, patients should
      undergo evaluation with esophageal motility testing, endoscopy, 24-h esophageal
      pH monitoring, and in some cases, sensory tests. Once the diagnosis of FCP has
      been established, treatment options rely on controlling patients' symptoms.
      Medical treatment has focused predominantly on medications that target pain, such
      as antidepressants and other pain neuromodulators. Non-pharmacologic
      interventions with complementary behavioral treatments, such as cognitive
      behavioral therapy, biofeedback, and hypnosis, have recently been recognized as
      useful in FCP patients. The latest findings on the evaluation and treatment of
      FCP are outlined herein.

PMID- 27709334
TI  - Editorial.

PMID- 27709335
TI  - Abstracts of papers presented at the International Symposium on Mechanisms of
      Airways Obstruction, March 28-31, 1978, University of Stellenbosch, Parowvallei,
      South Africa.

PMID- 27709333
TI  - Metabolites with Gram-negative bacteria quorum sensing inhibitory activity from
      the marine animal endogenic fungus Penicillium sp. SCS-KFD08.
AB  - Three new compounds named penicitor A, aculene E and penicitor B, as well as four
      known compounds, were isolated from the fermentation broth of Penicillium sp. SCS
      KFD08 associated with a marine animal Sipunculus nudus from the Haikou bay of
      China. Their planar structures and absolute configurations were unambiguously
      elucidated by spectroscopic data, Mosher's method, CD spectrum analysis along
      with quantum ECD calculation. Among them, compounds 2-7 showed quorum sensing
      inhibitory activity against Chromobacterium violaceum CV026, and could
      significantly reduce violacein production in N-hexanoyl-l-homoserine lactone (C6
      HSL) induced C. violaceum CV026 cultures at sub-inhibitory concentrations.

PMID- 27709338
TI  - Abstracts of the Scientific Communications at the Annual Meeting of the Swiss
      Society for Respiratory Diseases, Lausanne, April 28-29, 1978.

PMID- 27709332
TI  - Interactions Between Inflammatory Bowel Disease Drugs and Chemotherapy.
AB  - OPINION STATEMENT: As new and effective novel therapies in inflammatory bowel
      disease (IBD) become available, patients are living longer with advancing age and
      are at increased risk for malignancy. The management of IBD and malignancy
      involves multiple combinations of chemotherapy agents and IBD drugs, with the
      potential for interactions between these therapies. Interactions may either
      potentiate the effectiveness of drug class or exacerbate their common side
      effects. In this review article, we present a guide on studied interactions
      between IBD therapies and chemotherapy agents, specifically those of colorectal
      cancer, breast cancer, non-Hodgkin's lymphoma, and melanoma. The pharmacology and
      pharmocokinetics of each IBD drug will be discussed. Then, the IBD drug and
      chemotherapy interactions are summarized in table format. This guide will provide
      a quick reference to guide clinicians with this challenging management of two
      disease processes.

PMID- 27709336
TI  - ?

PMID- 27709341
TI  - Editorial.

PMID- 27709342
TI  - The role of elastases in the development of emphysema.
AB  - Enzymes which degrade elastin can disorganize the network of elastic fibers in
      the lungs of experimental animals and produce emphysema. Two sources of
      endogenous elastases in the lung are neutrophils and alveolar macrophages. The
      neutrophil elastase is an intracellular, granule-associated enzyme which is
      inhibited by alpha1-antitrypsin and has the capacity to produce emphysema in
      experimental animals. The recently identified macrophage elastase appears to be a
      secretory enzyme, not associated with granules and less effectively inhibited by
      alpha1-antitrypsin. The demonstration that macrophages from cigarette smokers
      release elastase in culture, and that cigarette smoke interferes with the action
      of inhibitors of elastase, suggests that elastases may be involved in the
      pathogenesis of emphysema in man. Further research is needed to establish whether
      degradation of elastin occurs in humans developing emphysema.

PMID- 27709349
TI  - Bathing in carbon dioxide-enriched water alters protein expression in
      keratinocytes of skin tissue in rats.
AB  - Beneficial effects of balneotherapy using naturally occurring carbonated water
      (CO2 enriched) have been known since the Middle Ages. Although this therapy is
      clinically applied for peripheral artery disease and skin disorder, the
      underlying mechanisms are not fully elucidated.Under controlled conditions, rats
      were bathed in either CO2-enriched water (CO2 content 1200 mg/L) or tap water,
      both at 37  degrees C, for 10 min daily over 4 weeks. Proliferation activity was
      assessed by Ki67 immunohistochemistry of the epidermis of the abdomen. The
      capillary density was assessed by immunodetection of isolectin-positive cells.
      Using cryo-fixed abdominal skin epidermis, follicle cells and stroma tissue
      containing capillaries were separately isolated by means of laser microdissection
      and subjected to proteomic analysis using label-free technique. Differentially
      expressed proteins were validated by immunohistochemistry.Proliferation activity
      of keratinocytes was not significantly different in the epidermis after bathing
      in CO2-enriched water, and also, capillary density did not change. Proteomic
      analysis revealed up to 36 significantly regulated proteins in the analyzed
      tissue. Based on the best expression profiles, ten proteins were selected for
      immunohistochemical validation. Only one protein, far upstream element binding
      protein 2 (FUBP2), was similarly downregulated in the epidermis after bathing in
      CO2-enriched water with both techniques. Low FUBP2 expression was associated with
      low c-Myc immune-expression in keratinocytes.Long-term bathing in CO2-enriched
      water showed a cellular protein response of epithelial cells in the epidermis
      which was detectable by two different methods. However, differences in
      proliferation activity or capillary density were not detected in the normal skin.

PMID- 27709350
TI  - Effect of Side-Specific Valvular Shear Stress on the Content of Extracellular
      Matrix in Aortic Valves.
AB  - Responses of valve endothelial cells (VECs) to shear stresses are important for
      the regulation of valve durability. However, the effect of flow patterns
      subjected to VECs on the opposite surfaces of the valves on the production of
      extracellular matrix (ECM) has not yet been investigated. This study aims to
      investigate the response of side-specific flow patterns, in terms of ECM
      synthesis and/or degradation in porcine aortic valves. Aortic and ventricular
      sides of aortic valve leaflets were exposed to oscillatory and laminar flow
      generated by a Cone-and-Plate machine for 48 h. The amount of collagen, GAGs and
      elastin was quantified and compared to samples collected from the same leaflets
      without exposing to flow. The results demonstrated that flow is important to
      maintain the amount of GAGs and elastin in the valve, as compared to the effect
      of static conditions. Particularly, the laminar waveform plays a crucial role on
      the modulation of elastin in side-independent manner. Furthermore, the ability of
      oscillatory flow on the aortic surface to increase the amount of collagen and
      GAGs cannot be replicated by exposure of an identical flow pattern on the
      ventricular side of the valve. Side-specific responses to the particular patterns
      of flow are important to the regulation of ECM components. Such understanding is
      imperative to the creation of tissue-engineered heart valves that must be created
      from the "appropriate" cells that can replicate the functions of the native VECs
      to regulate the different constituents of ECM.

PMID- 27709351
TI  - Adverse effects of non-hormonal pharmacological interventions in breast cancer
      survivors, suffering from hot flashes: A systematic review and meta-analysis.
AB  - PURPOSE: To access frequency and severity of adverse effects (AE) of non-hormonal
      drugs (NHD) for hot flashes in breast cancer survivors compared to controls and
      analyze adverse-effect risk by reviewing published randomized trials. METHODS:
      Cochrane Central Register for Controlled Trials, Embase, Medline, PsycINFO and
      PubMed databases were searched. Trials were included where participants were
      survivors of breast cancer suffering from hot flashes, treatment included self
      administered venlafaxine, gabapentin or clonidine, and AE were reported. AE
      frequency and severity were graded. A meta-analysis of ten trials with sub-group
      analyses was conducted. RESULTS: Forty-nine studies were identified, and 12 were
      included. A total of 1467 participants experienced 772 adverse effects, 81 % (n =
      627) in the treatment group and 19 % (n = 145) in the control group. Sixty-seven
      percent of AE was graded as mild and 33 % as moderate. The frequency of AE for
      NHD was overall significant compared to placebo. Sub-group analysis indicated
      that AE frequency and severity increased at higher doses of venlafaxine and
      gabapentin compared to placebo. CONCLUSION: The odds for experiencing AE was
      significantly higher in patients randomized to high-dose NHD than those
      randomized to controls, including placebo, low-dose medication and acupuncture.
      These therapies should be considered as a potential treatment alternative.

PMID- 27709352
TI  - A prospective study to assess the clinical utility of serum HER2 extracellular
      domain in breast cancer with HER2 overexpression.
AB  - PURPOSE: We explored the clinical utility of human epidermal growth factor
      receptor-2 extracellular domain (HER2/ECD) in patients treated for an invasive
      breast cancer with HER2 overexpression. METHODS: We prospectively studied
      HER2/ECD levels in the sera of 334 women included between 2007 and 2014, all
      treated with trastuzumab. HER2/ECD levels were measured at diagnosis, during
      treatments, and along the follow-up. We investigated the relationship of HER2/ECD
      with other clinicopathological parameters at diagnosis, its prognosis value, and
      its utility during the monitoring of a neoadjuvant treatment and the follow-up.
      RESULTS: Elevated HER2/ECD at diagnosis correlated positively with parameters
      associated with tumor aggressiveness. Disease-free survival of non-metastatic
      patients was significantly shorter in patients with high HER2/ECD at diagnosis
      (HR = 13.6, 95 % CI 1.6-113.6, P < 0.0001). Progression-free survival of
      metastatic patients was better for patients with low HER2/ECD (HR = 2.6, 95 % CI
      1.2-5.3, P = 0.033). A multivariate analysis revealed that HER2/ECD level at
      diagnosis was an independent prognosis factor. During neoadjuvant therapy, a
      significant decrease in HER2/ECD was reported only for the complete histological
      response group (P = 0.031). During the follow-up, HER2/ECD helped predict
      relapse, disease progression, and metastases before imaging in 18.6 % cases of
      the studied cohort. CONCLUSIONS: HER2/ECD is a prognosis factor that is valuable
      in evaluating the neoadjuvant treatment efficiency. HER2/ECD also appears to be a
      helpful surveillance biomarker for the early diagnosis of relapses and to predict
      the fate of metastases. This study brings evidences to support the use of
      HER2/ECD in the management of HER2-positive breast cancer.

PMID- 27709355
TI  - Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug
      delivery.
AB  - In this study, dissolving microneedles (MNs) were used to enhance ocular drug
      delivery of macromolecules. MNs were fabricated using polyvinylpyrrolidone (PVP)
      polymer of various molecular weights (MWs) containing three model molecules of
      increasing MW, namely fluorescein sodium and fluorescein isothiocyanate-dextrans
      (with MW of 70 k and 150 k Da). Arrays (3 * 3) of PVP MNs with conical shape
      measuring about 800 MUm in height with a 300 MUm base diameter, containing the
      model drugs, were fabricated and characterized for their fracture forces,
      insertion forces (in the sclera and cornea), depth of penetration (using OCT and
      confocal imaging), dissolution time and in vitro permeation. The average drug
      content of the MNs (only in MN shafts) ranged from 0.96 to 9.91 MUg, and the
      average moisture content was below 11 %. High MW PVP produced MNs that can
      withstand higher forces with minimal reduction in needle height. PVP MNs showed
      rapid dissolution that ranged from 10 to 180 s, which was dependent upon PVP's
      MW. In vitro studies showed significant enhancement of macromolecule permeation
      when MNs were used, across both the corneal and scleral tissues, in comparison to
      topically applied aqueous solutions. Confocal images showed that the
      macromolecules formed depots within the tissues, which led to sustained
      permeation. However, use of MNs did not significantly benefit the permeation of
      small molecules; nevertheless, MN application has the potential for drug
      retention within the selected ocular tissues unlike topical application for small
      molecules. The material used in the fabrication of the MNs was found to be
      biocompatible with retinal cells (i.e. ARPE-19). Overall, this study reported the
      design and fabrication of minimally invasive rapidly dissolving polymeric MN
      arrays which were able to deliver high MW molecules to the eye via the
      intrastromal or intrascleral route. Thus, dissolving MNs have potential
      applications in enhancing ocular delivery of both small and macromolecules.

PMID- 27709356
TI  - Prevalence of avian haemosporidian parasites is positively related to the
      abundance of host species at multiple sites within a region.
AB  - Parasite prevalence is thought to be positively related to host population
      density owing to enhanced contagion. However, the relationship between prevalence
      and local abundance of multiple host species is underexplored. We surveyed birds
      and their haemosporidian parasites (genera Plasmodium and Haemoproteus) at
      multiple sites across eastern North America to test whether the prevalence of
      these parasites in a host species at a particular site is related to that host's
      local abundance. Prevalence was positively related to host abundance within most
      sites, although the effect was stronger and more consistent for Plasmodium than
      for Haemoproteus. In contrast, prevalence was not related to variation in the
      abundance of most individual host species among sites across the region. These
      results suggest that parasite prevalence partly reflects the relative abundances
      of host species in local assemblages. However, three nonnative host species had
      low prevalence despite being relatively abundant at one site, as predicted by the
      enemy release hypothesis.

PMID- 27709360
TI  - Mediterranean meal versus Western meal effects on postprandial ox-LDL, oxidative
      and inflammatory gene expression in healthy subjects: a randomized controlled
      trial for nutrigenomic approach in cardiometabolic risk.
AB  - AIMS: Inflammation and oxidative damage contribute significantly to the
      development of cardiovascular diseases (CVD). Postprandial oxidative stress and
      inflammation are characterized by an increased susceptibility of the organism
      toward oxidative damage after consumption of a meal rich in lipids and/or
      carbohydrates. Micronutrients modulate immune system and exert a protective
      action by reducing oxidized low-density lipoprotein (ox-LDL) level. The aim of
      the present study was to evaluate the postprandial plasma ox-LDL level and the
      gene expression of 13 genes related to oxidative stress (HOSp) and human
      inflammasome pathways (HIp), after a tocopherol-enriched Mediterranean meal
      (TEM), and a Western high-fat meal (HFM). Moreover, Mediterranean Adequacy Index
      was calculated to define the quality of both meals. METHODS: We set up a
      randomized and crossover trial in healthy human volunteers. Ox-LDL level was
      measured by enzyme-linked immunosorbent assay and the gene expression of 13 genes
      related to HOSp and HIp by qRT-PCR. RESULTS: Ox-LDL levels significantly
      decreased comparing HFM versus TEM (p < 0.05). Percentages of significantly
      overexpressed genes after each dietary treatment are as follows: (A) baseline
      versus HFM: 7.69 % HIp and 23.08 % HOSp; (B) baseline versus TEM: 7.69 % HIp and
      7.69 % HOSp; (C) HFM versus TEM: 15.38 % HIp and 15.38 % HOSp. CONCLUSIONS: TEM
      reduced postprandial risk factors of CVD, such as ox-LDL, and the expression of
      inflammation and oxidative stress-related genes. Chronic studies on larger
      population are necessary before definitive conclusions. TRIAL REGISTRATION:
      ClinicalTrials.gov Id: NCT01890070.

PMID- 27709361
TI  - Macroscopic features predict outcome in patients with pancreatic ductal
      adenocarcinoma.
AB  - As macroscopic appearance represents tumor microenvironment, it may also reflect
      the biological and clinicopathological characteristics of a cancer. The aim of
      the study was to evaluate the clinicopathological significance of the gross
      appearance of pancreatic ductal adenocarcinoma (PDA). We investigated fresh
      macroscopic features in 352 cases of PDA and their clinicopathological
      significance. Three unique gross features were found: a honeycomb-like appearance
      (diffusely distributed microcysts and interstitial fibrotic thickening),
      macroscopic necrosis, and a tube/branching structure (apparent small cylindrical
      or linear structure). A honeycomb-like appearance was present in 24 cases (6.8 %)
      and significantly associated with low serum CA19-9 level and well-differentiated
      adenocarcinoma. Macroscopic necrosis was present in 235 cases (66.8 %) and
      significantly correlated with tumor size, nodal metastasis, nerve plexus
      invasion, no adjuvant chemotherapy, and distant recurrence. The presence of
      macroscopic necrosis was significantly associated with shorter disease-specific
      survival (DSS) and disease-free survival (DFS). The presence of larger areas of
      necrosis (>=2 mm) was closely associated with shorter survival. A tube/branching
      structure was found in 179 cases (50.9 %), which was correlated with larger tumor
      size and no adjuvant chemotherapy and macroscopic necrosis. The presence of a
      tube/branching structure was significantly associated with shorter DSS and DFS.
      Multivariate survival analyses showed that the presence of tube/branching
      structures was an independent negative prognostic factor in patients having PDA.
      We suggest that the gross appearance of PDA reflects clinicopathological
      characteristics and may be useful in predicting prognosis.

PMID- 27709362
TI  - Physeal histological morphology after thermal epiphysiodesis using radiofrequency
      ablation.
AB  - BACKGROUND: Several treatments have been described for leg length discrepancy.
      Epiphysiodesis is the most commonly used because of its effectiveness. Thermal
      epiphysiodesis using radiofrequency ablation (RFA) alters the growth plate
      morphology without damaging the adjacent articular cartilage; it is a minimally
      invasive method that has shown excellent results in animal models. This study
      describes the macro and micro morphology after the procedure. MATERIALS AND
      METHODS: Epiphysiodesis using RFA was performed in vivo for 8 min (92-98  degrees
      C) at two ablation sites (medial and lateral) in one randomly-selected tibia in
      eight growing pigs. The contralateral tibia was used as control. After 12 weeks,
      the pigs were killed and the tibiae harvested. The specimens were studied
      macroscopically and histology samples were obtained. Physeal morphology,
      thickness and characteristics were then described. RESULTS: Macroscopically, the
      articular cartilage was normal in all the treated tibiae. Microscopically, the
      physis was detected as a discontinuous line on the treated tibiae while it was
      continuous in all controls. In the control specimens, the mean thickness of the
      physis was 625 um (606-639, SD = 14). All the physeal layers were organized. In
      the ablated specimens, disorganized layers in a heterogeneous line were observed.
      Bone bridges were identified at the ablation sites. The central part of the
      physis looked normal. Next to the bone bridge, the physis was thicker and
      presented fibrosis. The mean thickness was 820 um (628-949, SD = 130). No
      abnormalities in the articular cartilage were observed. CONCLUSIONS: Thermal
      epiphysiodesis with RFA disrupts the physeal morphology and causes the formation
      of bone bridges at the ablation sites. This procedure does not damage the
      adjacent articular cartilage. The damaged tissue, next to the bone bridges, is
      characterized by disorganization and fibrosis.

PMID- 27709363
TI  - Sexually Explicit Media Use by Sexual Identity: A Comparative Analysis of Gay,
      Bisexual, and Heterosexual Men in the United States.
AB  - Advances in production and distribution of sexually explicit media (SEM) online
      have resulted in widespread use among men. Limited research has compared contexts
      of use and behaviors viewed in Internet SEM by sexual identity. The current study
      examined differences in recent SEM use (past 6 months) by sexual identity among
      an ethnically diverse sample of 821 men who completed an online survey in 2015.
      Both gay and bisexual men reported significantly more frequent use of Internet
      SEM compared to heterosexual men. Although most participants reported viewing SEM
      at home (on a computer, tablet, or smartphone), significantly more gay men
      reported SEM use at a sex party or commercial sex venue than either heterosexual
      or bisexual men. Sexual identity predicted viewing of high-risk and protective
      behaviors in separate logistic regression models. Specifically, compared to
      heterosexual men, gay and bisexual men had increased odds of viewing condomless
      anal sex (gay OR 5.20, 95 % CI 3.35-8.09; bisexual OR 3.99, 95 % CI 2.24-7.10)
      and anal sex with a condom (gay OR 3.93, 95 % CI 2.64-5.83; bisexual OR 4.59, 95
      % CI 2.78-7.57). Compared to gay men, heterosexual and bisexual men had increased
      odds of viewing condomless vaginal sex (heterosexual OR 27.08, 95 % CI 15.25
      48.07; bisexual OR 5.59, 95 % CI 3.81-8.21) and vaginal sex with a condom
      (heterosexual OR 7.90, 95 % CI 5.19-12.03; bisexual OR 4.97, 95 % CI 3.32-7.44).
      There was also evidence of identity discrepant SEM viewing as 20.7 % of
      heterosexual-identified men reported viewing male same-sex behavior and 55.0 % of
      gay-identified men reported viewing heterosexual behavior. Findings suggest the
      importance of assessing SEM use across media types and contexts and have
      implications for research to address the potential influence of SEM on sexual
      behavior (e.g., investigate associations between viewing condomless vaginal sex
      and engaging in high-risk encounters with female partners).

PMID- 27709366
TI  - Erratum to: P2Y1, P2Y2, and TRPV1 Receptors Are Increased in Diarrhea-Predominant
      Irritable Bowel Syndrome and P2Y2 Correlates with Abdominal Pain.

PMID- 27709365
TI  - Food selection in relation to nutritional chemistry of Cao Vit gibbons in Jingxi,
      China.
AB  - The Cao Vit gibbon (Nomascus nasutus) has only one population with about 110
      individuals living in a degraded karst forest along the China-Vietnam border.
      Investigation of food choice in relation to chemical nutrition will offer
      important insights into its conservation. We studied the food choice of two
      groups of Cao Vit gibbons using instantaneous scan sampling in Bangliang National
      Nature Reserve, Guangxi, China, over 4 years, and analyzed the chemical
      components (total nitrogen, TN; water-soluble sugar, WSS; crude fat, CF; neutral
      detergent fiber, NDF; acid detergent fiber, ADF; acid detergent lignin, ADL;
      condensed tannin, CT; and ash) of 48 food plant parts and 22 non-food plant
      parts. Fruits and figs that are rich in sugar are important food resources for
      gibbons. For other food types, flowers are a good source of total nitrogen and
      carbohydrates, and leaves and buds provide sources of protein and minerals. Cao
      Vit gibbons selected fruits that contain less total nitrogen, less acid detergent
      fiber and more water-soluble sugar than non-food fruits. Several food species
      that were heavily consumed by Cao Vit gibbons are suggested as potential tree
      species for ongoing habitat restoration.

PMID- 27709364
TI  - beta-Adrenergic modulation of cancer cell proliferation: available evidence and
      clinical perspectives.
AB  - PURPOSE: In this review, we aimed to present and discuss the available
      preclinical and epidemiological evidences regarding the modulation of cancer cell
      proliferation by beta-adrenoceptors (beta-AR), with a specific focus on the
      putative effects of beta-blockers according to their pharmacological properties.
      METHODS: A comprehensive review of the published literature was conducted, and
      the evidences concerning the involvement of beta-AR in cancer as well as the
      possible role of beta-blockers were selected and discussed. RESULTS: The majority
      of reviewed studies show that: (1) All the cancer types express both beta1- and
      beta2-AR, with the exception of neuroblastoma only seeming to express beta2-AR;
      (2) adrenergic agonists are able to increase proliferation of several types of
      cancers; (3) the proliferative effect seems to be mediated by both beta1- and
      beta2-AR; (4) binding to beta-AR results in a cAMP transient flux which activates
      two major downstream effector systems: protein kinase A and EPAC and (5) beta
      blockers might be putative adjuvants for cancer treatment. CONCLUSIONS: Overall,
      the reviewed studies show strong evidences that beta-AR activation, through
      several intracellular mechanisms, modulate tumor cell proliferation suggesting
      beta-blockers can be a feasible therapeutic approach to antagonize beta
      adrenergic response or have a protective effect per se. This review highlight the
      need for intensifying the research not only on the molecular mechanisms
      underlying the beta-adrenergic influence in cancer, but also on the implications
      of biased agonism of beta-blockers as potential antitumor agents.

PMID- 27709368
TI  - Do deep ulnar intraneural ganglion cysts demonstrate a shared but unrecognized
      propagation pattern?

PMID- 27709369
TI  - Citation analysis of puerperal and menstrual psychosis.
AB  - A citation analysis of more than 2500 works on the childbearing and menstrual
      psychoses has shown that the average number of citations is 1 % of the literature
      or less; Anglo-Saxon authors have the lowest standards of scholarship. Many
      excellent works have received few of no citations. Attention is drawn to citation
      fraud and the pernicious effect of superficial "reviews."

PMID- 27709367
TI  - A test of the reward-value hypothesis.
AB  - Rats retain source memory (memory for the origin of information) over a retention
      interval of at least 1 week, whereas their spatial working memory (radial maze
      locations) decays within approximately 1 day. We have argued that different
      forgetting functions dissociate memory systems. However, the two tasks, in our
      previous work, used different reward values. The source memory task used multiple
      pellets of a preferred food flavor (chocolate), whereas the spatial working
      memory task provided access to a single pellet of standard chow-flavored food at
      each location. Thus, according to the reward-value hypothesis, enhanced
      performance in the source memory task stems from enhanced encoding/memory of a
      preferred reward. We tested the reward-value hypothesis by using a standard 8-arm
      radial maze task to compare spatial working memory accuracy of rats rewarded with
      either multiple chocolate or chow pellets at each location using a between
      subjects design. The reward-value hypothesis predicts superior accuracy for high
      valued rewards. We documented equivalent spatial memory accuracy for high- and
      low-value rewards. Importantly, a 24-h retention interval produced equivalent
      spatial working memory accuracy for both flavors. These data are inconsistent
      with the reward-value hypothesis and suggest that reward value does not explain
      our earlier findings that source memory survives unusually long retention
      intervals.

PMID- 27709370
TI  - Biomechanical evaluation of cornea in patients with ankylosing spondylitis.
AB  - PURPOSE: The aim of this study was to evaluate the corneal biomechanical
      parameters in patients with ankylosing spondylitis (AS) and to compare them with
      the healthy subjects. METHODS: Sixty patients with AS (study group) and 60
      healthy subjects (control group) were enrolled in this prospective study. The
      study group was further classified as active (n:30) and inactive (n:30). After
      detailed ophthalmological examination including intraocular pressure (IOP)
      measurement with Goldmann applanation tonometer (IOPGAT), corneal hysteresis
      (CH), corneal resistance factor (CRF), corneal-compensated IOP (IOPcc), and
      Goldmann-correlated IOP (IOPg) were measured with the Reichert Ocular Response
      Analyzer (ORA). Central corneal thickness (CCT) was measured with the Spectral
      Domain Optical Coherence Tomography (SD-OCT). RESULTS: The study group's mean CH,
      CCT, IOPg, and IOPGAT values were lower than the control group (p < 0.05 for all
      variables). The mean CH, CRF, CCT, IOPg, and IOPGAT values were higher in active
      patients when compared to the inactive ones (p < 0.001, p < 0.001, p = 0.013, p =
      0.021, and p = 0.002, respectively). CONCLUSIONS: AS patients have lower CCT, CH,
      IOPg, and IOPGAT when compared with healthy subjects. In the active stage of AS,
      patients present with higher levels of corneal biomechanical parameters with
      thicker corneas. IOPcc is a more accurate measurement than IOPGAT or IOPg in AS
      patients.

PMID- 27709371
TI  - Visual outcomes after lensectomy and iris claw artisan intraocular lens
      implantation in patients with Marfan syndrome.
AB  - PURPOSE: To review our experience with crystalline lens extraction and iris claw
      Artisan IOL implantation in patients with lens subluxation secondary to Marfan
      syndrome. METHODS: A retrospective analysis of 12 eyes of 9 patients with lens
      subluxation due to Marfan syndrome who underwent crystalline lens removal and
      Artisan IOL (Ophtec, Groningen, Netherlands) implantation. A questionnaire of pre
      and post-operative data, including demographics, pre- and postoperative
      comorbidities and complications was completed. Patients were evaluated for visual
      outcome and occurrence of complications. Uncorrected visual acuity (UCVA), best
      corrected visual acuity (BCVA), and spherical equivalents (SE) were compared
      before and after lens extraction and IOL insertion. RESULTS: The mean age of the
      participants was 30.03 +/- 15.02 years, and mean post-operative follow-up time
      was 44.5 +/- 16.4 months. Mean BCVA also showed a significant improvement from
      0.5 +/- 0.3 at the baseline to 0.2 +/- 0.2 post-operatively (P = 0.006). SE
      changed significantly from -11.38 +/- 1.99 preoperatively to -0.45 +/- 1.65 post
      operatively (P = 0.003). All eyes had the IOL implanted at desired position. Post
      operative complications were retinal detachment in one case and IOL dislocation
      in another patient. No other complication such as ocular hypertension, angle
      abnormalities, clinical cystoids macular edema, and corneal decompensation was
      observed during the follow-up period. CONCLUSION: Artisan IOL implantation after
      lens extraction appears to be an attractive alternative for optical correction in
      cases of Marfan syndrome with ectopia lentis. It confers a significant
      improvement in visual acuity with reasonable risk profile.

PMID- 27709372
TI  - Genomic analyses identify agents regulating somatotroph and lactotroph functions.
AB  - Isolated hormone deficiency might be caused by loss of a specific type of
      endocrine cells, and regenerating these missing cells may provide a new option
      for future treatment. It is known that POU1F1 lineage cells can differentiate
      into thyrotroph, somatotroph, and lactotroph. However, there is no effective way
      of controlling pituitary stem/progenitor cells to differentiate into a specific
      type of endocrine cell. We thereby analyzed multiple genomic publications related
      to POU1F1 and pituitary development in this study to identify genes and agents
      regulating POU1F1 lineage cell differentiation. ANOVA analyses were performed to
      obtain differentially expressed genes. Ingenuity pathway analyses were performed
      to obtain signaling pathways, interaction networks, and upstream regulators. Venn
      diagram was used to determine the overlapping information between studies.
      Summary statistics was performed to rank genes according to their frequency of
      occurrence in these studies. The results from upstream analyses indicated that
      326 agents may regulate pituitary cell differentiation. These agents can be
      categorized into 12 groups, including hormones and related pathways, PKA-cAMP
      pathways, p53/DNA damaging/cell cycle pathways, immune/inflammation regulators,
      growth factor and downstream pathways, retinoic/RAR pathways, ROS pathways,
      histone modifications, CCAAT/enhancer binding protein family, neuron
      development/degeneration pathways, calcium related and fat acid, and glucose
      pathways. Additional experiments demonstrated that H2O2 and catalase
      differentially regulate growth hormone and prolactin expression in
      somatolactotroph cells, confirming potential roles of ROS pathway on regulating
      somatotroph and lactotroph functions.

PMID- 27709373
TI  - Novel SNPs and InDels discovered in two promoter regions of porcine pregnancy
      associated glycoprotein 2-like subfamily (pPAG2-Ls) in crossbreed pigs.
AB  - This is a pioneer study of single nucleotide polymorphisms (SNPs) within the
      entire promoter region (1204 bp) of the dominant pPAG2-L subfamily in the pig.
      The pPAG2-L subfamily was sequenced/examined using genomic deoxyribonucleic acid
      (gDNA) templates of crossbreed pigs (Landrace x Large White), and compared to two
      bacterial artificial chromosome (BAC) clones containing gDNA of the Duroc breed
      (as the positive controls). Our analysis of the pPAG2-L promoter identified 31
      SNPs and one InDel mutation in crossbreed pigs. Among 42 SNPs identified in two
      BAC clones, 24 SNPs had not been previously detected in crossbreed pigs. The
      sequence alignment of pPAG2-L promoter, performed with Lasagne-Search 2.0,
      Cluster Bluster and MatInspector software, revealed a total of 28 transcription
      factor binding sites (TFBS) and 10 TFBS (AP-1, CCAAT, CHOP:C, FOXP1, LSF, MRF-2,
      Myc, NF1, NF-Y, TGIF) within SNPs in the core sequences. It was noted that TFBS
      (NF1) was found to be unique to the pPAG2 promoter sequence containing SNPs: g.
      1100G>A(R), g.-1101T>C(Y), represented by GA and TC genotypes (p x  = 0.12). Our
      broad-based novel database thus provides an SNP PAG2-L pattern for modern
      genotyping of female and male progenitors. This is required for further studies
      of various potential correlations between guiding SNP genotypes of the pPAG2-L
      subfamily in the sows of many breeds, in which the most economically important
      reproductive traits are properly documented on each farm.

PMID- 27709375
TI  - Carbohydrates-chitosan composite carrier for Vero cell culture.
AB  - In this study, carbohydrate-chitosan composite including glucose-chitosan,
      sucrose-chitosan and starch-chitosan with varied carbohydrate concentrations were
      prepared as carriers for Vero cell culture. Our results show that among these
      composites, 30 % starch-chitosan composite (STC) were the best carriers for the
      growth of Vero cells. The initial number of attached cells on the surface of
      composite carriers did not have any significant effect on subsequent cell
      production. A higher glucose level in the growth medium during the exponential
      phase of cell growth, however, played an important factor for cell production.
      Vero cells on the STC carriers were able to convert starch inside the composite
      carriers into glucose and further utilized the glucose for their growth.
      Moreover, by crosslink with serum the STC carriers supported an even better cell
      production in the normal medium without adding fetal bovine serum, as well as a
      good extracellular virus production. The STC composite is therefore a promising
      alternative carrier for Vero cell culture.

PMID- 27709376
TI  - Explication and Definition of Mental Health Recovery: A Systematic Review.
AB  - This review assessed the concordance of the literature on recovery with the
      definition and components of recovery developed by the Substance Abuse and Mental
      Health Services Administration (SAMHSA). Each SAMHSA identified recovery
      component was first explicated with synonyms and keywords and made mutually
      exclusive by authors. Inter-rater reliability was established on the coding of
      the presence of 17 recovery components and dimensions in 67 literature reviews on
      the recovery concept in mental health. The review indicated that concordance
      varied across SAMHSA components. The components of recovery with greatest
      concordance were: individualized/person centered, empowerment, purpose, and hope.

PMID- 27709377
TI  - Erratum to: Dominant and Non-Dominant Frequency Structure of Evoked Ventricular
      Fibrillation in Dogs with Myocardial Ischemia.

PMID- 27709374
TI  - Exploring drought stress-regulated genes in senna (Cassia angustifolia Vahl.): a
      transcriptomic approach.
AB  - De novo assembly of reads produced by next-generation sequencing (NGS)
      technologies offers a rapid approach to obtain expressed gene sequences for non
      model organisms. Senna (Cassia angustifolia Vahl.) is a drought-tolerant annual
      undershrub of Caesalpiniaceae, a subfamily of Fabaceae. There are insufficient
      transcriptomic and genomic data in public databases for understanding the
      molecular mechanism underlying the drought tolerance of senna. Therefore, the
      main purpose of this study was to know the transcriptome profile of senna, with
      special reference to drought stress. RNA from two different stages of leaf
      development was extracted and sequenced separately using the Illumina technology.
      A total of 200 million reads were generated, and a de novo assembly of processed
      reads in the pooled transcriptome using Trinity yielded 43,413 transcripts which
      were further annotated using NCBI BLAST with "green plant database (txid 33090),"
      Swiss Prot, Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of
      Orthologous Groups (COG), and Gene Ontology (GO). Out of the total transcripts,
      42,280 (95.0 %) were annotated by BLASTX against the green plant database of
      NCBI. Senna transcriptome showed the highest similarity to Glycine max (41 %),
      followed by Phaseolus vulgaris (16 %), Cicer arietinum (15 %), and Medicago
      trancatula (5 %). The highest number of GO terms were enriched for the molecular
      functions category; of these "catalytic activity" (GO: 0003824) (25.10 %) and
      "binding activity" (GO: 0005488) (20.10 %) were most abundantly represented. We
      used InterProscan to see protein similarity at domain level; a total of 33,256
      transcripts were annotated against the Pfam domains. The transcripts were
      assigned with various KEGG pathways. Coding DNA sequences (CDS) encoding various
      drought stress-regulated pathways such as signaling factors, protein
      modifying/degrading enzymes, biosynthesis of phytohormone, phytohormone
      signaling, osmotically active compounds, free radical scavengers, chlorophyll
      metabolism, leaf cuticular wax, polyamines, and protective proteins were
      identified through BLASTX search. The lucine-rich repeat kinase family was the
      most abundantly found group of protein kinases. Orphan, bHLH, and bZIP family TFs
      were the most abundantly found in senna. Six genes encoding MYC2 transcription
      factor, 9-cis-epoxycarotenoid dioxygenase (NCED), l -ascorbate peroxidase (APX),
      aminocyclopropane carboxylate oxidase (ACO), abscisic acid 8'-hydroxylase (ABA),
      and WRKY transcription factor were confirmed through reverse transcriptase-PCR
      (RT-PCR) and Sanger sequencing for the first time in senna. The potential drought
      stress-related transcripts identified in this study provide a good start for
      further investigation into the drought adaptation in senna. Additionally, our
      transcriptome sequences are the valuable resource for accelerated genomics
      assisted genetic improvement programs and facilitate manipulation of biochemical
      pathways for developing drought-tolerant genotypes of crop plants.

PMID- 27709378
TI  - Substrate Specificity of Na+,Cl-(HCO3-)-ATPase.
AB  - We studied substrate specificity of Na+,Cl-(HCO3-)-ATPase. In most cases,
      replacement of ATP for other phosphate-containing substances resulted in not only
      pronounced suppression of phosphohydrolase reactions, but also dramatic changes
      of their responsiveness to the stimulating effect of monovalent ions. The data
      showed that Na+,Cl-(HCO3-)-ATPase is a highly specific enzyme for ATP.

PMID- 27709379
TI  - Compensatory Changes in the Brain Dopaminergic System of WAG/Rij Rats Genetically
      Predisposed to Absence Epilepsy.
AB  - Involvement of the brain dopaminergic system in the age-related dynamics of
      absence epilepsy in WAG/Rij rats was examined by histological,
      immunohistochemical, and electrophysiological (EEG) methods. We revealed reduced
      expression of dopamine receptors in various brain structures prior to first
      manifestations of the disease (at the age of 1-3 months), reduced density of
      neurons in the center of nigrostriatal system (substantia nigra pars compacta) in
      10-month-old rats in comparison with 1-month-old rats, and positive correlation
      between neural density in the substantia nigra and intensity of epileptic
      activity in EEG. It is hypothesized that loss of dopaminergic neurons and reduced
      nigrostriatal dopaminergic innervation of the brain could prevent the development
      of absence epilepsy in WAG/Rij rats.

PMID- 27709380
TI  - Effect of Metabolic Stress on Coenzyme Q10 Content in Tissues of Active and
      Passive Rats.
AB  - The dynamics of coenzyme Q10 concentration in the blood plasma, liver, and brain
      of passive and active rats was studied on the model of metabolic stress. This
      parameter was shown to differ in rats with various patterns of behavior. Dietary
      consumption of coenzyme Q10 in doses of 10 and 100 mg/kg body weight was followed
      by changes in its content in experimental animals.

PMID- 27709381
TI  - Combined Effect of Low-Intensity Helium-Neon Laser and X-Ray Radiation on in Vivo
      Cellular Response of the Whole Blood and Lymphoid Organs in Mice.
AB  - We studied the effect of exposure to helium-neon laser (dose range 0.16-50
      mJ/cm2) on activation of natural protection reserve in mice using the adaptive
      response test. DNA comets method revealed a protective response manifested in DNA
      damage level in whole blood leukocytes of mice and in lymphoid organs by the
      thymus and spleen weight index; preexposure to laser did not induce the adaptive
      response. ROS level in the whole blood was assessed by the level of zymosan
      induced luminol chemiluminescence. In mice subjected to adaptive laser
      irradiation in doses of 0.16-5 mJ/cm2 followed by X-ray irradiation in a dose of
      1.5 Gy, the activation index calculated as the ratio of induced to spontaneous
      area of luminescence was by 1.4 times lower than that in non-irradiated animals,
      which attested to reduced ROSgeneration reserve capacity of neutrophils.

PMID- 27709382
TI  - Effect of Doxazosin on Autonomic Nervous Control and Urodynamics of Rat Urinary
      Bladder during Modeled Infravesical Obstruction.
AB  - The therapeutic effect of doxazosin (40 MUg/kg/day over one month) on urinary
      bladder was examined in female rats with modeled chronic infravesical obstruction
      (IVO) produced by graduated mechanical constriction of the proximal urethral
      segment. In one month, IVO induced a pronounced vesical hypertrophy both in
      treated and untreated rats that manifested in increased bladder weight and
      capacity, the latter increment being pronouncedly greater in treated rats. In
      untreated IVO rats, infusion cystometry revealed elevated basal intravesical
      pressure of void bladder P0, markedly increased maximal (premicturitional)
      pressure Pmax, and increased amplitude of spontaneous oscillations of
      intravesical pressure DeltaPdet in filled bladder. Doxazosin produced no
      significant effect on Pmax rise during IVO, but prevented elevation of P0 and
      increment of DeltaPdet in filled bladder. During gradual filling of urinary
      bladder in control (intact) rats, the parasympathetic vesical influences
      increased progressively, while in untreated IVO rats, the adrenergic influences
      prevailed even at maximal filling of the bladder. In IVO rats, doxazosin
      prevented the bias of the sympathetic-parasympathetic balance in the filled
      bladder in favor of sympathetic influences, but did not prevent this bias in a
      void bladder. It is hypothesized that alpha-adrenoblockers improve micturition
      during IVO caused by benign prostatic hyperplasia not only by decreasing the
      urethral resistance to urine flow due to down-regulation of prostate smooth
      muscle tone, but also by a direct action of these blockers on detrusor adrenergic
      receptors and central structures involved in urinary bladder control.

PMID- 27709383
TI  - Effect of Granulocyte Colony-Stimulating Factor Immobilized by the Electron-Beam
      Synthesis Nanotechnology on Reparative Regeneration of Spermatogenous Tissue.
AB  - Effectiveness of the granulocyte colony-stimulating factor immobilized by using
      electronbeam synthesis nanotechnology was investigated on the model of
      experimental testicular failure caused by the toxic effect on stem spermatogonia.
      Administration of the drug to experimental paclitaxel-treated animals increased
      the number of sources of the proliferative pool of spermatogenesis and its
      productivity. The effectiveness of immobilized granulocyte colony-stimulating
      factor was based on its ability to stimulate reparative regeneration of the
      spermatogenic tissue, which manifested in a decrease in spermatogenic layer
      maturity and increase in the number of microenvironment cells. Effectiveness of
      the immobilized form of the drug was superior to that of non-immobilized form.

PMID- 27709384
TI  - Effects of Humic Acids Isolated from Peat of Various Origin on in Vitro
      Production of Nitric Oxide: a Screening Study.
AB  - A screening study of biological activity of native humic acids isolated from peat
      was performed; several physical and chemical parameters of their structures were
      studied by UV- and infrared spectroscopy. Spectroscopy yielded similar shape of
      light absorption curves of humic acids of different origin, which can reflect
      similarity of general structural principles of these substances. Alkaline humic
      acids have more developed system of polyconjugation, while molecular structures
      of pyrophosphate humic acids were characterized by higher aromaticity and
      condensation indexes. Biological activity of the studied humic acids was assessed
      by NO-stimulating capacity during their culturing with murine peritoneal
      macrophages in a wide concentration range. It was shown that due to dose
      dependent enhancement of NO production humic acids can change the functional
      state of macrophages towards development of pro-inflammatory properties. These
      changes were associated with high activity of humic acids isolated by
      pyrophosphate extraction, which allows considering effects of isolation method on
      biological activity.

PMID- 27709385
TI  - Spatial Memory in the Progeny of Rats Subjected to Different Types of
      Experimental Preeclampsia.
AB  - Spatial memory was studied in 2-month-old offspring of rats subjected to
      different types of experimental preeclampsia (replacement of drinking water with
      1.8% NaCl from day 1 to 21 of gestation or intraperitoneal administration of non
      selective NO-synthase inhibitor L-NAME to pregnant rats in a daily dose of 25
      mg/kg for 7 days on gestation days 14-20). Spatial memory was evaluated in an
      elevated 8-arm radial maze. Both types of experimental preeclampsia impaired
      spatial (long-term and short-term) memory and can be used in the development of
      drugs correcting negative effects of this pregnancy complication on memory.

PMID- 27709386
TI  - Inhibition of Apoptosis is a Potential Way to Improving Ischemic Brain Tolerance
      in Combined Exposure to Hypercapnia and Hypoxia.
AB  - We compared the intensity of apoptosis in the peri-infarction area of the brain
      after isolated and combined exposure to hypoxia and hypercapnia prior to focal
      ischemic stroke modeling. Hypoxia and hypercapnia reduced the number of TUNEL
      positive cells in the peri-infarction area, and their combination was most
      effective in comparison with effects of isolated exposures. The maximum
      neuroprotective effect of combined exposure to hypoxia and hypercapnia in
      comparison with isolated exposures was determined by inhibition of apoptosis in
      the peri-infarction zone.

PMID- 27709387
TI  - Dihydroquercetin Does Not Affect Age-Dependent Increase in Blood Pressure and
      Angiotensin-Converting Enzyme Activity in the Aorta of Hypertensive Rats.
AB  - We analyzed changes in angiotensin-converting enzyme activity in the aorta of
      hypertensive SHR rats against the background of age-related BP increase (from
      week 7 to 14) and the effect of dihydroquercetin on BP rise and angiotensin
      converting enzyme activity. Normotensive WKY rats of the same age were used as
      the control. BP and activity of angiotensin-converting enzyme in the aorta of SHR
      rats increased with age. Dihydroquercetin in doses of 100 and 300 MUg/kg per day
      had no effect on the increase of these parameters; dihydroquercetin administered
      to 14-week-old WKY rats in a dose of 300 MUg/kg reduced activity of the
      angiotensin-converting enzyme. Thus, the early (7-14 weeks) increase in BP and
      angiotensin-converting enzyme activity in the aorta of SHR rats was not modified
      by flavonoids (dihydroquercetin) in contrast to other rat strains and humans,
      which is indicative of specificity of hypertension mechanism in SHR rats.

PMID- 27709388
TI  - Effect of Hedgehog Signaling Pathway Activation on Proliferation of High-Grade
      Gliomas.
AB  - We studied the effect of an activator (ShTh) and an inhibitor (cyclopamine) of
      the Hedgehog signaling pathway on proliferation of human glioma cell lines U87-MG
      and U251-MG and cultured human astrocytes. The Hedgehog signaling pathway is
      activated in glioma cells, but not in cultured human astrocytes. Experiments with
      Shh and cyclopamine can serve as an additional criterion for assessing activity
      of Hedgehog signaling in known cell lines and primary cultured cells.

PMID- 27709389
TI  - Effect of ROS Inhalation on Systemic and Local Hemodynamics in Rats.
AB  - The effects of inhalation of singlet oxygen mixture, dry and humidified ozone
      oxygen mixture, and ozonated oils on heart rate variability as well as on the
      rate and control mechanisms of microcirculation were examined in rats. The most
      optimal were the responses of systemic and regional hemodynamics to inhalation of
      the gas produced by a generator of singlet oxygen and humidified ozone-oxygen
      mixtures. Singlet oxygen stabilized the cardiac rhythm and augmented
      microcirculation via activation of "internal" (endothelial and neurogenic)
      regulatory mechanisms.

PMID- 27709390
TI  - Audiovisual Stimulation Modulates Physical Performance and Biochemical and
      Hormonal Status of Athletes.
AB  - We studied the effect of audiovisual stimulation training course on physical
      development, functional state of the cardiovascular system, blood biochemical
      parameters, and hormonal status of athletes. The training course led to
      improvement of physical performance and adaptive capacities of the circulatory
      system, increase in plasma levels of total protein, albumin, and glucose and
      total antioxidant activity, and decrease in triglyceride, lipase, total
      bilirubin, calcium, and phosphorus. The concentration of hormones (cortisol,
      thyrotropin, triiodothyronine, and thyroxine) also decreased under these
      conditions. In the control group, an increase in the concentration of creatinine
      and uric acid and a tendency toward elevation of lowdensity lipoproteins and
      total antioxidant activity were observed in the absence of changes in cardiac
      function and physical performance; calcium and phosphorus concentrations reduced.
      The improvement in functional state in athletes was mainly associated with
      intensification of anabolic processes and suppression of catabolic reactions
      after audiovisual stimulation (in comparison with the control). Stimulation was
      followed by an increase in the number of correlations between biochemical and
      hormonal changes and physical performance of athletes, which attested to better
      integration of processes at the intersystem level.

PMID- 27709391
TI  - EEG-fMRI Study of Alpha-Stimulation Neurobiofeedback Training Course.
AB  - fMRI-EEG dynamics of brain activity in volunteers was studied during the course
      of EEG alpha-stimulation training (20 sessions). Twenty-three healthy men (20-35
      years) were subjected to 3-fold mapping in a feedback loop (EEG alpha-rhythm
      biofeedback with acoustic reinforcement). This procedure was performed at the
      beginning, middle, and end of the course. During the first neurofeedback training
      session, deactivation (p<0.001) was found in the right angular gyrus,
      supramarginal, and superior temporal gyri, Brodmann area 39, and cerebellum.
      Activation (p<0.001) was observed in the medial frontal and cingulate gyri, motor
      areas of both hemispheres, and Brodmann area 32. During final (third)
      neurofeedback training session, we observed strong deactivation (p<0.05 with FDR)
      of zones responsible for spatial thinking and motor functions: left medial
      frontal and left medial temporal gyri; right postcentral, lingual, and superior
      frontal gyri; insula and right side of the cerebellum; and precuneus and cuneus
      (Brodmann areas 6, 9, 7, 31, 8, 13, and 22). Changes in the alpha wave power were
      most pronounced in the primary and secondary somatosensory cortex of the left
      hemisphere (Brodmann areas 2L and 5L).

PMID- 27709392
TI  - Functional State of the Heart during Spontaneous Nonconvulsive Seizure Activity
      at Various Times of the Day.
AB  - Circadian peculiarities of HR regulation and functional capacities of the heart
      in WAG/Rij rats with genetically determined absence epilepsy are related to spike
      wave activity of the brain. The number of spike-wave discharges (SWD) is maximum
      at night, early morning, and evening time and decreases to minimum at 08.00
      16.00. At night, functional capacities of the heart are reduced and stress test
      at night induces ischemic changes in the myocardium at a lower functional load
      than in the daytime (low level of SWD activity). The decrease in the number of
      SWD and spike-wave index during the daytime contributes to the central mechanisms
      of autonomic regulation of the heart. However, these capacities are reduced
      against the background of increased seizure activity during nighttime.

PMID- 27709393
TI  - Immunotropic Properties of Immobilized Interferon-alpha2b.
AB  - Course treatment with IFN-alpha2b immobilized on polyethylene glycol stimulates
      phagocytic activity of peritoneal macrophages and neutrophils, enhances humoral
      immune response in CBA/CaLac mice, stimulates IL-4 synthesis, and suppresses IFN
      gamma production by mitogenstimulated splenocytes from experimental animals.

PMID- 27709394
TI  - Subfoveal choroidal thickness in polypoidal choroidal vasculopathy after
      switching to intravitreal aflibercept injection.

PMID- 27709396
TI  - Our genes, our selves: hereditary breast cancer and biological citizenship in
      Norway.
AB  - In this paper we explore the rise of 'the breast cancer gene' as a field of
      medical, cultural and personal knowledge. We address its significance in the
      Norwegian public health care system in relation to so-called biological
      citizenship in this particular national context. One of our main findings is
      that, despite its claims as a measure for health and disease prevention, gaining
      access to medical knowledge of BRCA 1/2 breast cancer gene mutations can also
      produce severe instability in the individuals and families affected. That is,
      although gene testing provides modern subjects with an opportunity to foresee
      their biological destiny and thereby become patients in waiting, it undoubtedly
      also comes with difficult existential dilemmas and choices, with implications
      that resonate beyond the individual and into different family and love relations.
      By elaborating on this finding we address the question of whether the empowerment
      slogan, which continues to be advocated through various health, BRCA and breast
      cancer discourses, reinforces a naive or an idealized notion of the actively
      responsible patient: resourceful enough to seek out medical expertise and gain
      sufficient knowledge, on which to base informed decisions, thereby reducing the
      future risk of developing disease. In contrast to this ideal, our Norwegian
      informants tell a different story, in which there is no apparent heroic mastery
      of genetic fates, but rather a pragmatic attitude to dealing with a dire
      situation over which they have little control, despite having complied with
      medical advice through national guidelines and follow-up procedures for BRCA 1/2
      carriers. In conclusion we claim that the sense of safety that gene testing and
      its associated medical solutions allegedly promise to provide proved illusory.
      Although BRCA-testing offers the potential for protection from adverse DNA
      heritage, administered through possibilities for self-monitoring and self
      management of the body, the feeling of 'being in good health' has hardly been
      reinforced by the emergence of gene technology.

PMID- 27709397
TI  - Large-scale monitoring of effects of clothianidin-dressed oilseed rape seeds on
      pollinating insects in Northern Germany: effects on red mason bees (Osmia
      bicornis).
AB  - The aim of this study was to investigate the effects of Elado(r) (10 g
      clothianidin & 2 g beta-cyfluthrin/kg seed)-dressed oilseed rape on the
      development and reproduction of mason bees (Osmia bicornis) as part of a large
      scale monitoring field study in Northern Germany, where oilseed rape is usually
      cultivated at 25-33 % of the arable land. Both reference and test sites comprised
      65 km2 in which no other crops attractive to pollinating insects were present.
      Six study locations were selected per site and three nesting shelters were placed
      at each location. Of these locations, three locations were directly adjacent to
      oilseed rape fields, while the other three locations were situated 100 m distant
      from the nearest oilseed rape field. At each location, 1500 cocoons of O.
      bicornis were placed into the central nesting shelter. During the exposure phase,
      nest building activities and foraging behaviour were assessed repeatedly. Cocoons
      were harvested in autumn to assess parasitization and reproduction including
      larval development. The following spring, the emergence of the next generation of
      adults from cocoons was monitored. High reproductive output and low
      parasitization rates indicated that Elado(r)-dressed oilseed rape did not cause
      any detrimental effects on the development or reproduction of mason bees.

PMID- 27709395
TI  - Antimicrobial susceptibility and phylotyping profile of pathogenic Escherichia
      coli and Salmonella enterica isolates from calves and pigs in Minas Gerais,
      Brazil.
AB  - The aims of the present study were to determine (i) the profiles of phylogroup
      and (ii) the antimicrobial susceptibility of pathogenic Escherichia coli strains
      isolated from calves, and of Salmonella spp. strains isolated from calves and
      pigs in Minas Gerais State, Brazil. Sixty-one pathogenic E. coli strains and
      Salmonella spp. (n = 24) strains isolated from fecal samples of calves and
      Salmonella spp. (n = 39) strains previously isolated from fecal samples of
      growing/finishing pigs were tested. The minimum inhibitory concentration (MIC)
      using the agar dilution method was determined for nalidixic acid, amikacin,
      amoxicillin, ampicillin, cefoxitin, norfloxacin, gentamicin, tetracycline, and
      trimethoprim-sulfamethoxazole. All E. coli isolates were susceptible to amikacin.
      Tetracycline was the antimicrobial that presented the higher frequency of
      resistance among E. coli strains, followed by ampicillin, trimethoprim
      sulfamethoxazole, amoxicillin, nalidixic acid, norfloxacin, gentamicin, and
      cefoxitin. E. coli (n = 61) strains isolated from calves belonged to different
      phylogroup namely, phylogroup A (n = 26), phylogroup B1 (n = 31), phylogroup E (n
      = 3), and phylogroup F (n = 1). Phylogroups B2, C, and D were not identified
      among the E. coli in the present study. All Salmonella spp. (n = 24) strains
      isolated from fecal samples of calves were susceptible to amikacin, amoxicillin,
      ampicillin, norfloxacin, gentamicin, tetracycline, and trimethoprim
      sulfamethoxazole. Resistance to nalidixic acid and cefoxitin was detected in
      16.66 and 8.33 % of the Salmonella spp. strains, respectively. Among the
      Salmonella spp. (n = 39) strains isolated from fecal samples of pigs, the higher
      frequency of resistance was observed to tetracycline, followed by amoxicillin,
      gentamicin, ampicillin, trimethoprim-sulfamethoxazole, nalidixic acid, cefoxitin,
      and norfloxacin. All strains were susceptible to amikacin. Forty-eight (78.68 %)
      of the E. coli strains were classified as multidrug-resistant, whereas among
      Salmonella spp. strains, the percentage of multidrug resistance was 57.14 %,
      being all multidrug-resistant strains isolated from pigs (92.30 %). The results
      from the present study indicate a high frequency of antimicrobial resistance
      among pathogenic E. coli strains isolated from calves and Salmonella spp. strains
      isolated from pigs and a high rate of susceptibility to most antimicrobials
      tested among Salmonella spp. strains isolated from calves. Our study highlights
      the presence of multidrug-resistant strains of E. coli and Salmonella spp.
      isolated from food-producing animals in Minas Gerais, Brazil.

PMID- 27709398
TI  - Joint toxicity of cadmium and SDBS on Daphnia magna and Danio rerio.
AB  - Information on joint toxicity is limited. To clarify the joint toxicity and the
      interactions among toxicants on different aquatic organisms, we investigated the
      acute toxicity of cadmium and sodium dodecyl benzene sulfonate, two chemicals
      with high concerns in Chinese waters, on the immobilization of Daphnia magna (D.
      magna) and the swimming behavior of Danio rerio (D. rerio). Our results
      illustrated that cadmium and sodium dodecyl benzene sulfonate expressed a
      synergistic effect on the immobilization of D. magna; and an antagonistic effect
      on the swimming speed D. rerio, but a synergistic effect on its vertical position
      in the water column. Based on the observed data, we found the independent action
      model was more appropriate than the concentration addition model in the
      prediction of their joint toxicity. Our results gave an example of the joint
      toxicity investigation, and aided to comprehensive the toxicity action mode of
      chemical mixtures.

PMID- 27709399
TI  - Review of field and monitoring studies investigating the role of nitro
      substituted neonicotinoid insecticides in the reported losses of honey bee
      colonies (Apis mellifera).
AB  - The nitro-substituted neonicotinoid insecticides, which include imidacloprid,
      thiamethoxam and clothianidin, are widely used to control a range of important
      agricultural pests both by foliar applications and also as seed dressings and by
      soil application. Since they exhibit systemic properties, exposure of bees may
      occur as a result of residues present in the nectar and/or pollen of seed- or
      soil-treated crop plants and so they have been the subject of much debate about
      whether they cause adverse effects in pollinating insects under field conditions.
      Due to these perceived concerns, the use of the three neonicotinoids
      imidacloprid, clothianidin and thiamethoxam has been temporarily suspended in the
      European Union for seed treatment, soil application and foliar treatment in crops
      attractive to bees. Monitoring data from a number of countries are available to
      assess the presence of neonicotinoid residues in honey bee samples and possible
      impacts at the colony level and these are reviewed here together with a number of
      field studies which have looked at the impact of clothiandin on honey bees in
      relation to specific crop use and in particular with oilseed rape. Currently
      there is considerable uncertainty with regards to the regulatory testing
      requirements for field studies. Accordingly, a testing protocol was developed to
      address any acute and chronic risks from oilseed rape seeds containing a coating
      with 10 g clothianidin and 2 g beta-cyfluthrin per kg seeds (Elado(r)) for
      managed honey bee (Apis mellifera) colonies, commercially bred bumble bee (Bombus
      terrestris) colonies and red mason bees (Osmia bicornis) as a representative
      solitary bee species. This is described here together with a summary of the
      results obtained as an introduction to the study details given in the following
      papers in this issue.

PMID- 27709400
TI  - Identification and characterization of an isolate of apple green crinkle
      associated virus involved in a severe disease of quince (Cydonia oblonga, Mill.).
AB  - A quince tree showing severe symptoms of a previously undescribed viral disease
      occurring in northern Apulia (Italy) was analysed using high-throughput
      sequencing of small RNA libraries, leading to the identification of a new strain
      of apple green crinkle associated virus (isolate AGCaV-CYD) showing peculiar
      traits. RT-PCR with specific primers detected AGCaV-CYD in consistent association
      with symptoms in the surveyed orchards. Molecular characterization of the
      reconstructed genome, together with phylogenetic analysis, showed it to be
      closely related to an AGCaV strain causing green crinkle disease in apple (AGCaV
      AUR) and divergent from the type strain of apple stem pitting virus (ASPV-PA66).

PMID- 27709402
TI  - Molecular characterization of a new human coxsackievirus B2 associated with
      severe hand-foot-mouth disease in Yunnan Province of China in 2012.
AB  - Human coxsackievirus B2 (CVB2) belongs to the species Human enterovirus B and can
      cause aseptic meningitis, myocarditis and hand-foot-mouth disease (HFMD). We
      first determined the complete genome of the RW41-2/YN/CHN/2012 strain, isolated
      from a patient with HFMD and aseptic meningitis in the Yunnan Province, China in
      2012. The strain shared 83.5 % and 82.2 % nucleotide similarity with CVB2
      prototype strain Ohio-1, in the complete VP1 gene and the complete genome,
      respectively. Using phylogenetic and homogeneity analyses for the complete VP1
      gene, CVB2 strains could be divided into four genogroups (A-D); the RW41
      2/YN/CHN/2012 strain belonging to genogroup D. The amino acid sequence of VP1 is
      highly conserved. Recombination analyses showed the newly isolated RW41
      2/YN/CHN/2012 strain was probably a recombinant, which was closely related to
      strain CVB2 (KM386639) in the genomic P1 and P2 regions and strains of other
      human enterovirus B (HEV-B) viruses (KT353721, JX644073, and KP262053) in the P3
      region.

PMID- 27709401
TI  - Construction of a recombinant duck enteritis virus vaccine expressing
      hemagglutinin of H9N2 avian influenza virus and evaluation of its efficacy in
      ducks.
AB  - H9 subtype avian influenza viruses (AIVs) remain a significant burden in the
      poultry industry and are considered to be one of the most likely causes of any
      new influenza pandemic in humans. As ducks play an important role in the
      maintenance of H9 viruses in nature, successful control of the spread of H9 AIVs
      in ducks will have significant beneficial effects on public health. Duck
      enteritis virus (DEV) may be a promising candidate viral vector for aquatic
      poultry vaccination. In this study, we constructed a recombinant DEV, rDEV-?UL2
      HA, inserting the hemagglutinin (HA) gene from duck-origin H9N2 AIV into the UL2
      gene by homologous recombination. One-step growth analyses showed that the HA
      gene insertion had no effect on viral replication and suggested that the UL2 gene
      was nonessential for virus growth in vitro. In vivo tests further showed that the
      insertion of the HA gene in place of the UL2 gene did not affect the
      immunogenicity of the virus. Moreover, a single dose of 103 TCID50 of rDEV-?UL2
      HA induced solid protection against lethal DEV challenge and completely prevented
      H9N2 AIV viral shedding. To our knowledge, this is the first report of a DEV
      vectored vaccine providing robust protection against both DEV and H9N2 AIV virus
      infections in ducks.

PMID- 27709405
TI  - A Three-Step Latent Class Analysis to Identify How Different Patterns of Teen
      Dating Violence and Psychosocial Factors Influence Mental Health.
AB  - Although multiple forms (i.e., physical, threatening, psychological, sexual, and
      relational abuse) and patterns (i.e., perpetration and victimization) of violence
      can co-occur, most existing research examines these experiences individually.
      Thus, the purpose of this study is to investigate: (1) homogenous subgroups based
      on victimization and perpetration of multiple forms of teen dating violence; (2)
      predictors of membership in these subgroups; and (3) mental health consequences
      associated with membership in each subgroup. Nine hundred eighteen adolescents in
      the 9th or 10th grade at seven public high schools in Texas participated in the
      survey (56 % female, White: 30 %, Hispanic: 32 %, African American: 29 %, others:
      9 %). A three-step latent class analysis was employed. Five latent teen dating
      violence classes were identified: (1) nonviolence; (2) emotional/verbal abuse;
      (3) forced sexual contact; (4) psychological + physical violence; and (5)
      psychological abuse. Females, African Americans, and youth who had higher
      acceptance of couple violence scores and whose parents had less education were
      more likely to members of dating violence classes compared with the nonviolence
      class. Adolescents who experienced multiple types of dating violence reported
      greater mental health concerns. Prevention programs may benefit by identifying
      the homogenous subgroups of teen dating violence and targeting adolescent teen
      dating violence accordingly.

PMID- 27709403
TI  - Variation in the Types of Providers Participating in Breast Cancer Follow-Up
      Care: A SEER-Medicare Analysis.
AB  - BACKGROUND: The current guidelines do not delineate the types of providers that
      should participate in early breast cancer follow-up care (within 3 years after
      completion of treatment). This study aimed to describe the types of providers
      participating in early follow-up care of older breast cancer survivors and to
      identify factors associated with receipt of follow-up care from different types
      of providers. METHODS: Stages 1-3 breast cancer survivors treated from 2000 to
      2007 were identified in the Surveillance, Epidemiology and End results Medicare
      database (n = 44,306). Oncologist (including medical, radiation, and surgical)
      follow-up and primary care visits were defined using Medicare specialty provider
      codes and linked American Medical Association (AMA) Masterfile. The types of
      providers involved in follow-up care were summarized. Stepped regression models
      identified factors associated with receipt of medical oncology follow-up care and
      factors associated with receipt of medical oncology care alone versus combination
      oncology follow-up care. RESULTS: Oncology follow-up care was provided for 80 %
      of the patients: 80 % with a medical oncologist, 46 % with a surgeon, and 39 %
      with a radiation oncologist after radiation treatment. The patients with larger
      tumor size, positive axillary nodes, estrogen receptor (ER)-positive status, and
      chemotherapy treatment were more likely to have medical oncology follow-up care
      than older patients with higher Charlson comorbidity scores who were not
      receiving axillary care. The only factor associated with increased likelihood of
      follow-up care with a combination of oncology providers was regular primary care
      visits (>2 visits/year). CONCLUSIONS: Substantial variation exists in the types
      of providers that participate in breast cancer follow-up care. Improved guidance
      for the types of providers involved and delineation of providers'
      responsibilities during follow-up care could lead to improved efficiency and
      quality of care.

PMID- 27709406
TI  - Preliminary Effectiveness Study of Coping Power Program for Aggressive Children
      in Pakistan.
AB  - Aggression is a characteristic feature of many psychiatric disorders. To address
      the scarceness for evidence-based interventions for behavioral problems in
      Pakistan, we evaluated the effectiveness of culturally adapted version of Coping
      Power Program. The purpose of the study was to determine the extent to which
      Coping Power Program is capable of reducing aggressive behavior and improving
      competent behavior, when delivered in a different culture, i.e., Pakistan. With
      randomized control trial (RCT) of pre- and post-testing, 112 fourth grade boys
      were allocated to Coping Power intervention condition and waitlist control
      condition. The intervention group showed significant reduction in aggression at
      post assessment, in comparison to control group. Boys who received Coping Power
      intervention also showed improvements in behavior, social skills, and social
      cognitive processes, with better anger control and problem solving strategies, in
      comparison to the control group. The results of the study provide preliminary
      evidence, supporting the effectiveness of Coping Power Program for Pakistani
      children. Despite its limitations, the results of this study are promising and
      suggest that Coping Power is an effective intervention to reduce behavioral
      problems and promote healthy and positive behaviors in children, even when
      implemented in different contexts with greater potential for violence exposure.

PMID- 27709407
TI  - Sulfated glycosaminoglycans: their distinct roles in stem cell biology.
AB  - Sulfated glycosaminoglycan (GAG) chains are a class of long linear
      polysaccharides that are covalently attached to multiple core proteins to form
      proteoglycans (PGs). PGs are major pericellular and extracellular matrix
      components that surround virtually all mammalian cell surfaces, and create
      conducive microenvironments for a number of essential cellular events, such as
      cell adhesion, cell proliferation, differentiation, and cell fate decisions. The
      multifunctional properties of PGs are mostly mediated by their respective GAG
      moieties, including chondroitin sulfate (CS), heparan sulfate (HS), and keratan
      sulfate (KS) chains. Structural divergence of GAG chains is enzymatically
      generated and strictly regulated by the corresponding biosynthetic machineries,
      and is the major driving force for PG functions. Recent studies have revealed
      indispensable roles of GAG chains in stem cell biology and technology. In this
      review, we summarize the current understanding of GAG chain-mediated stem cell
      niches, focusing primarily on structural characteristics of GAG chains and their
      distinct regulatory functions in stem cell maintenance and fate decisions.

PMID- 27709408
TI  - Coupling of shear-circumferential stress pulses investigation through stress
      phase angle in FSI models of stenotic artery using experimental data.
AB  - Many cardiovascular diseases are closely associated with hemodynamic parameters.
      The main purpose of this study is mimicking a physiological blood flow in
      stenotic arteries to provide an understanding of hemodynamic parameters. An
      experimental setup was designed to produce original pulsatile flow and measure
      pressure pulse waves through a compliant tube. Moreover, a numerical model
      considering fluid-solid interaction was developed to investigate wall shear
      stress and circumferential stress waves, based on the results of the experiments.
      Results described elevated mean pressure by increasing stenosis severity
      especially at the critical obstacle of 50 %, which the pressure rose
      significantly and raised up by 10 mm Hg that may cause damage in endothelial
      cells. Increasing in stenosis severity led to: more negative wall shear stress
      and more oscillation of shear stress at the post-stenotic region and also more
      absolute value of angular phase difference between wall shear stress and
      circumferential stress waves at the stenotic throat. All of the aforementioned
      parameters determinant the endothelial cell pathology in predication of potential
      sites of progression of atherosclerotic plaques. Therefore, results can be
      applied in study of plaque growth and mechanisms of arterial remodeling in
      atherosclerosis.

PMID- 27709410
TI  - Innervation of the blood vessels of the spinal cord: a comprehensive review.
AB  - There is growing evidence that the nervous system influences spinal cord
      vasculature. However, most descriptions of the spinal cord have paid little
      attention to this important aspect. We reviewed the literature on the innervation
      of spinal cord vessels with an emphasis on findings that may be applicable to
      human medicine. Multiple neurotransmitters and competing theories have been
      implicated in the neural regulation of spinal cord blood vessels. Identifying
      valid mechanisms of pathogenesis could be beneficial to human patients with
      spinal cord lesions. We discuss the various findings on the neural mechanisms
      behind spinal cord blood flow. Further investigation is warranted due to the
      current emphasis on comparative animal studies without corresponding
      corroborative human findings.

PMID- 27709411
TI  - Patterns of Vasculature in Mouse Models of Lung Cancer Are Dependent on Location.
AB  - PURPOSE: Preclinical studies of hypoxia are generally done using ectopic
      xenograft tumors, which behave differently from human tumors. Our previous
      findings have shown that subcutaneously implanted lung tumors exhibit more
      hypoxia than their orthotopic implanted or spontaneous K-ras-induced
      counterparts. We hypothesize that differences in hypoxia are due to site-specific
      differences in vascularity and perfusion. PROCEDURES: To compare the presence and
      functionality of vessels in these tumor models, we studied vascular perfusion in
      vivo in real time. RESULTS: Orthotopically implanted and spontaneous K-ras
      induced lung tumors showed elevated perfusion, demonstrating vasculature
      functionality. Little contrast agent uptake was observed within the
      subcutaneously implanted tumors, indicating vascular dysfunction. These findings
      were corroborated at the microscopic level with Hoechst 33342 and Meca-32
      staining. CONCLUSIONS: From these observations, we concluded that differences in
      hypoxia in experimental models is related to vessel perfusion. Thus, appropriate
      selection of preclinical lung tumor models is essential for the study of hypoxia,
      angiogenesis and therapies targeting these phenomena.

PMID- 27709412
TI  - Acromegalic osteopathy.
AB  - Acromegalic osteopathy is an emerging complication of acromegaly characterized by
      increase in bone turnover, deterioration in bone microarchitecture and high risk
      of vertebral fractures. Vertebral fractures, as diagnosed by a radiological and
      morphometric approach, occur in about one-third of acromegaly patients in close
      relationship with duration of active disease. However, the prediction of
      vertebral fractures in this clinical setting is still a matter of uncertainty,
      since the pathogenesis of acromegalic osteopathy is multifactorial and fractures
      may occur even in presence of normal bone mineral density. In this narrative
      article, we summarize the pathophysiology and clinical aspects of acromegalic
      osteopathy.

PMID- 27709409
TI  - Radiation-induced gliomas: a comprehensive review and meta-analysis.
AB  - By conducting a systemic search of the PubMed database, we performed a
      comprehensive literature review to characterize secondary gliomas following
      radiotherapy treatment and to determine the most appropriate treatment strategy.
      Our analysis included 296 cases of radiation-induced gliomas. The primary lesion
      was characterized as a hematological malignancy in 104 cases (35.1 %), pituitary
      adenoma in 35 (11.8 %), craniopharyngioma in 19 (6.4 %), medulloblastoma in 38
      (12.8 %), germ cell tumor in 13 (4.3 %), low-grade glioma in 28 (9.4 %),
      cancer/sarcoma in 12 (4.0 %), scalp region disease in 15 (5.0 %),
      meningioma/schwannoma in 13 (4.3 %), metastatic brain tumor in 5 (1.6 %), and
      other types (e.g., arteriovenous malformations and angiomas) in 14 (4.7 %). The
      average age of onset for primary lesions was 16.0 +/- 15.8 years, and the average
      radiation dose delivered to the primary lesion was 37.6 +/- 20.0 Gy. Secondary
      gliomas could be divided into grade I (1), grade II (32), grade III (88), and
      grade IV (173) tumors. The median overall survival for all glioma cases was 11
      months (95 % confidence interval [CI], 9-12), with a 2-year survival rate of 20.2
      %. On multivariate analysis, combined modality treatment and the latency period
      from the radiotherapy treatment to the glioma diagnosis were variables associated
      with the overall survival of patients with grade III/IV secondary gliomas. For
      patients treated with cranial radiotherapy, the risk of secondary glioma
      incidence warrants a longer follow-up period beyond the standard time frame
      typically designated for determining the risk of primary tumor relapse. Moreover,
      combination therapy is a potential treatment option for radiation-induced
      gliomas.

PMID- 27709413
TI  - Immune Cell Metabolism in Systemic Lupus Erythematosus.
AB  - Cellular metabolism represents a newly identified checkpoint of effector
      functions in the immune system. A solid body of work has characterized the
      metabolic requirements of normal T cells during activation and differentiation
      into polarized effector subsets. Similar studies have been initiated to
      characterize the metabolic requirements for B cells and myeloid cells. Only a few
      studies though have characterized the metabolism of immune cells in the context
      of autoimmune diseases. Here, we review what is known on the altered metabolic
      patterns of CD4+ T cells, B cells, and myeloid cells in lupus patients and lupus
      prone mice and how they contribute to lupus pathogenesis. We also discuss how
      defects in immune metabolism in lupus can be targeted therapeutically.

PMID- 27709415
TI  - Pathology of Human Pheochromocytoma and Paraganglioma Xenografts in NSG Mice.
AB  - A major impediment to the development of effective treatments for metastatic or
      unresectable pheochromocytomas and paragangliomas has been the absence of valid
      models for pre-clinical testing. Attempts to establish cell lines or xenografts
      from human pheochromocytomas and paragangliomas have previously been
      unsuccessful. NOD-scid gamma (NSG) mice are a recently developed strain lacking
      functional B-cells, T-cells, and NK cells. We report here that xenografts of
      primary human paragangliomas will take in NSG mice while maintaining their
      architectural and immunophenotypic characteristics as expressed in the patients.
      In contrast to grafts of cell lines and of most common types of primary tumors,
      the growth rate of grafted paragangliomas is very slow, accurately representing
      the growth rate of most pheochromocytomas and paragangliomas even in metastases
      in humans. Although the model is therefore technically challenging, primary
      patient-derived xenografts of paragangliomas in NSG mice provide a potentially
      valuable new tool that could prove especially valuable for testing treatments
      aimed at eradicating the small tumor deposits that are often numerous in patients
      with metastatic paraganglioma.

PMID- 27709414
TI  - Sensing photosynthetic herbicides in an electrochemical flow cell.
AB  - Specific inhibitory reactions of herbicides with photosynthetic reaction centers
      bound to working electrodes were monitored in a conventional electrochemical cell
      and a newly designed microfluidic electrochemical flow cell. In both cases, the
      bacterial reaction centers were bound to a transparent conductive metal oxide,
      indium-tin-oxide, electrode through carbon nanotubes. In the conventional cell,
      photocurrent densities of up to a few MUA/cm2 could be measured routinely. The
      photocurrent could be blocked by the photosynthetic inhibitor terbutryn (I 50 =
      0.38 +/- 0.14 MUM) and o-phenanthroline (I 50 = 63.9 +/- 12.2 MUM). The
      microfluidic flow cell device enabled us to reduce the sample volume and to
      simplify the electrode arrangement. The useful area of the electrodes remained
      the same (ca. 2 cm2), similar to the classical electrochemical cell; however, the
      size of the cell was reduced considerably. The microfluidic flow control enabled
      us monitoring in real time the binding/unbinding of the inhibitor and cofactor
      molecules at the secondary quinone site.

PMID- 27709416
TI  - 1H, 15N and 13C resonance assignments for free and IEEVD peptide-bound forms of
      the tetratricopeptide repeat domain from the human E3 ubiquitin ligase CHIP.
AB  - The ubiquitin ligase CHIP catalyzes covalent attachment of ubiquitin to unfolded
      proteins chaperoned by the heat shock proteins Hsp70/Hsc70 and Hsp90. CHIP
      interacts with Hsp70/Hsc70 and Hsp90 by binding of a C-terminal IEEVD motif found
      in Hsp70/Hsc70 and Hsp90 to the tetratricopeptide repeat (TPR) domain of CHIP.
      Although recruitment of heat shock proteins to CHIP via interaction with the CHIP
      TPR domain is well established, alterations in structure and dynamics of CHIP
      upon binding are not well understood. In particular, the absence of a structure
      for CHIP-TPR in the free form presents a significant limitation upon studies
      seeking to rationally design inhibitors that may disrupt interactions between
      CHIP and heat shock proteins. Here we report the 1H, 13C, and 15N backbone and
      side chain chemical shift assignments for CHIP-TPR in the free form, and backbone
      chemical shift assignments for CHIP-TPR in the IEEVD-bound form. The NMR
      resonance assignments will enable further studies examining the roles of dynamics
      and structure in regulating interactions between CHIP and the heat shock proteins
      Hsp70/Hsc70 and Hsp90.

PMID- 27709417
TI  - Reformation of tissue balls from tentacle explants of coral Goniopora lobata:
      self-organization process and response to environmental stresses.
AB  - Coral has strong regeneration ability, which has been applied for coral
      production and biodiversity protection via tissue ball (TB) culture. However, the
      architecture, morphological processes, and effects of environmental factors on TB
      formation have not been well investigated. In this study, we first observed TB
      formation from the cutting tentacle of scleractinia coral Goniopora lobata and
      uncovered its inner organization and architecture by confocal microscopy. We then
      found that the cutting tentacle TB could self-organize and reform a solid TB
      (sTB) in the culture media. Using chemical drug treatment and dissection
      manipulation approaches, we demonstrated that the mechanical forces for bending
      and rounding of the cutting fragments came from the epithelial cells, and the
      cilia of epithelial cell played indispensable roles for the rounding process.
      Environmental stress experiments showed that high temperature, not CO2-induced
      acidification, affected TB and sTB formation. However, the combination of high
      temperature and acidification caused additional severe effects on sTB
      reformation. Our studies indicate that coral TB has strong regeneration ability
      and therefore could serve as a new model to further explore the molecular
      mechanism of TB formation and the effects of environmental stresses on coral
      survival and regeneration.

PMID- 27709419
TI  - Residency Diary: The Beginning of My Second Year: June and July 2016.

PMID- 27709418
TI  - Proliferation of rabbit chondrocyte and inhibition of IL-1beta-induced apoptosis
      through MEK/ERK signaling by statins.
AB  - Chondrocyte plays a critical role in endochondral ossification and cartilage
      repair by maintaining the cartilaginous matrix. Statins have been widely used to
      lower the cholesterol level in patients with cardiovascular disorders. Previous
      research has demonstrated potential role of statins in chondrocyte proliferation.
      This study addresses the proliferation-regulatory effect of lovastatin in rabbit
      chondrocytes as well as the underlying signaling mechanisms, thereby exploring
      its potential application in chondrocyte-related disorders, such as cartilage
      damage and osteoarthritis. Rabbit chondrocytes were treated with lovastatin at
      multiple concentrations, and the proliferation rate was measured by CCK-8 test.
      The results showed significant increase in chondrocyte proliferation under
      lovastatin treatment. Using real-time quantitative PCR, it was observed that the
      expression levels of COL2A1, SOX-9, Caspase-3, and MMP-3 genes were significantly
      changed by lovastatin treatment. Western blotting analysis showed that the
      abundance of COL2A1, SOX-9, MEK1/2, p-MEK1/2, ERK1/2, p-ERK1/2, Caspase-3, and
      MMP-3 proteins was also significantly influenced by lovastatin treatment.
      Interleukine-1 beta (IL-1beta) is involved in the progression of osteoarthritis
      (OA) by inducing articular cartilage and chondrocyte aging and senescence. In
      this study, we observed that lovastatin treatment inhibited IL-1beta-induced
      chondrocyte apoptosis, while the combined treatment of lovastatin and U0126
      evidently offset the apoptosis-inhibiting effect of lovastatin in chondrocyte
      proliferation. The expressional level and protein abundance of COL2A1, SOX-9,
      MEK1/2, p-MEK1/2, ERK1/2, p-ERK1/2, caspase-3, and MMP-3 genes showed significant
      alterations under the combined treatment. Together, our results suggested that
      lovastatin significantly promoted proliferation and inhibited the IL-1beta
      induced apoptosis in rabbit chondrocytes, which was mediated by the MEK/ERK
      signaling.

PMID- 27709420
TI  - Cochrane in CORR (r): Topical Application of Tranexamic Acid for the Reduction of
      Bleeding (Review).

PMID- 27709421
TI  - CORR Insights(r): Are PEEK-on-Ceramic Bearings an Option for Total Disc
      Arthroplasty? An In Vitro Tribology Study.

PMID- 27709423
TI  - Kampo formula "Hochu-ekki-to" suppressed carbon tetrachloride-induced
      hepatotoxicity in mice.
AB  - OBJECTIVE: The aim of this study was to investigate whether pretreatment with the
      Japanese herbal medicine "Hochu-ekki-to" (TJ-41) has an ameliorative effect on
      carbon tetrachloride (CCl4)-induced hepatotoxicity through anorexia prevention.
      METHODS: Twenty-four hours before CCl4 injection, TJ-41 or saline solution was
      intraperitoneally administered. Furthermore, 24 h after TJ-41 injection, mice
      were intraperitoneally administered 1.6 g/kg CCl4 or olive oil. Moreover, 24 h
      after CCl4/olive oil injection, mice from each group were euthanized and bled for
      plasma analysis. RESULTS: Mice injected with CCl4 exhibited severe anorexia.
      Moreover, CCl4 increased the plasma levels of hepatic injury markers (i.e.,
      alanine aminotransferase and aspartate aminotransferase) as well as lipid
      peroxidation and hepatic Ca levels. Pretreatment with TJ-41 recovered the CCl4
      induced anorexia and plasma levels of the hepatic injury markers. Moreover, CCl4
      induced lipid peroxidation and hepatic Ca levels decreased upon TJ-41
      pretreatment. In addition, hepatic metallothionein levels in the TJ-41 + CCl4
      treated group were decreased by >50 % compared with the levels in the TJ-41
      treated group, implying that metallothionein was consumed by CCl4-induced
      radicals. CONCLUSION: Our results suggest that TJ-41 attenuates CCl4-induced
      hepatotoxicity, presumably by the induction of metallothionein, which in turn
      scavenges radicals induced by CCl4 exposure.

PMID- 27709424
TI  - Gastrointestinal microbiome and breast cancer: correlations, mechanisms and
      potential clinical implications.
AB  - Gastrointestinal microbiome plays as a symbiont which provides protection effect
      against invading pathogens, aids in the immune system development, nutrient
      reclamation and absorption as well as molecule breakdown. And it may avert
      carcinogenesis through these biological activities. By now, studies have been
      carried out to elaborate the association between gastrointestinal microbiome and
      breast cancer. It has been implicated that breast cancer was substantially
      associated with estrogen-dependent and estrogen-independent functions of
      gastrointestinal microbiome. Evidence from animal experiments also confirmed
      mammary tumor-related changes in microbial community. The possible mechanisms
      involve estrogen metabolism, immune regulation, obese status and so forth. Based
      on the current evidence, cues on future management strategies of breast cancer
      such as antibiotics and dietary interventions are proposed. In conclusion, large
      scale clinical studies and bench-based researches are needed to validate the
      associations and elaborate the mechanisms, so as to reduce the risk of breast
      cancer and improve the outcomes of those already diagnosed.

PMID- 27709422
TI  - How Does the dGEMRIC Index Change After Surgical Treatment for FAI? A Prospective
      Controlled Study: Preliminary Results.
AB  - BACKGROUND: Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) allows an
      objective, noninvasive, and longitudinal quantification of biochemical cartilage
      properties. Although dGEMRIC has been used to monitor the course of cartilage
      degeneration after periacetabular osteotomy (PAO) for correction of hip
      dysplasia, such longitudinal data are currently lacking for femoroacetabular
      impingement (FAI). QUESTIONS/PURPOSES: (1) How does the mean acetabular and
      femoral dGEMRIC index change after surgery for FAI at 1-year followup compared
      with a similar group of patients with FAI treated without surgery? (2) Does the
      regional distribution of the acetabular and femoral dGEMRIC index change for the
      two groups over time? (3) Is there a correlation between the baseline dGEMRIC
      index and the change of patient-reported outcome measures (PROMs) at 1-year
      followup? (4) Among those treated surgically, can dGEMRIC indices distinguish
      between intact and degenerated cartilage? METHODS: We performed a prospective,
      comparative, nonrandomized, longitudinal study. At the time of enrollment, the
      patients' decision whether to undergo surgery or choose nonoperative treatment
      was not made yet. Thirty-nine patients (40 hips) who underwent either joint
      preserving surgery for FAI (20 hips) or nonoperative treatment (20 hips) were
      included. The two groups did not differ regarding Tonnis osteoarthritis score,
      preoperative PROMs, or baseline dGEMRIC indices. There were more women (60%
      versus 30%, p = 0.003) in the nonoperative group and patients were older (36 +/-
      8 years versus 30 +/- 8 years, p = 0.026) and had lower alpha angles (65 degrees 
      +/- 10 degrees  versus 73 degrees  +/- 12 degrees , p = 0.022) compared with the
      operative group. We used a 3.0-T scanner and a three-dimensional dual flip-angle
      gradient-echo technique for the dGEMRIC technique for the baseline and the 1-year
      followup measurements. dGEMRIC indices of femoral and acetabular cartilage were
      measured separately on the initial and followup radial dGEMRIC reformats in
      direct comparison with morphologic radial images. Regions of interest were placed
      manually peripherally and centrally within the cartilage based on anatomic
      landmarks at the clockface positions. The WOMAC, the Hip disability and
      Osteoarthritis Outcome Score, and the modified Harris hip score were used as
      PROMs. Among those treated surgically, the intraoperative damage according to the
      Beck grading was recorded and compared with the baseline dGEMRIC indices.
      RESULTS: Although both the operative and the nonoperative groups experienced
      decreased dGEMRIC indices, the declines were more pronounced in the operative
      group (-96 +/- 112 ms versus -16 +/- 101 ms on the acetabular side and -96 +/-
      123 ms versus -21 +/- 83 ms on the femoral side in the operative and nonoperative
      groups, respectively; p < 0.001 for both). Patients undergoing hip arthroscopy
      and surgical hip dislocation experienced decreased dGEMRIC indices; the decline
      in femoral dGEMRIC indices was more pronounced in hips after surgical hip
      dislocation (-120 +/- 137 ms versus -61 +/- 89 ms, p = 0.002). In the operative
      group a decline in dGEMRIC indices was observed in 43 of 44 regions over time. In
      the nonoperative group a decline in dGEMRIC indices was observed in four of 44
      regions over time. The strongest correlation among patients treated surgically
      was found between the change in WOMAC and baseline dGEMRIC indices for the entire
      joint (R = 0.788, p < 0.001). Among those treated nonoperatively, no correlation
      between baseline dGEMRIC indices and change in PROMs was found. In the
      posterosuperior quadrant, the dGEMRIC index was higher for patients with intact
      cartilage compared with hips with chondral lesions (592 +/- 203 ms versus 444 +/-
      205 ms, p < 0.001). CONCLUSIONS: We found a decline in acetabular, femoral, and
      regional dGEMRIC indices for the surgically treated group at 1-year followup
      despite an improvement in all PROMs. We observed a similar but less pronounced
      decrease in the dGEMRIC index in symptomatic patients without surgical treatment
      indicating continuous cartilage degeneration. Although treatment of FAI is
      intended to alter the forces acting across the hip by eliminating impingement,
      its effects on cartilage biology are not clear. dGEMRIC provides a noninvasive
      method of assessing these effects. Longer term studies will be needed to
      determine whether the matrix changes of the bradytrophic cartilage seen here are
      permanent or clinically important. LEVEL OF EVIDENCE: Level II, therapeutic
      study.

PMID- 27709425
TI  - Epigenome-wide DNA methylation analysis in siblings and monozygotic twins
      discordant for sporadic Parkinson's disease revealed different epigenetic
      patterns in peripheral blood mononuclear cells.
AB  - Numerous studies have elucidated the genetics of Parkinson's disease; however,
      the aetiology of the majority of sporadic cases has not yet been resolved. We
      hypothesized that epigenetic variations could be associated with PD and evaluated
      the DNA methylation pattern in PD patients compared to brothers or twins without
      PD. The methylation of DNA from peripheral blood mononuclear cells of 62
      discordant siblings including 24 monozygotic twins was characterized with
      Illumina DNA Methylation 450K bead arrays and subsequently validated in two
      independent cohorts: 221 PD vs. 227 healthy individuals (cohort 1) applying
      Illumina's VeraCode and 472 PD patients vs. 487 controls (cohort 2) using
      pyrosequencing. We choose a delta beta of >15 % and selected 62 differentially
      methylated CpGs in 51 genes from the discordant siblings. Among them, three
      displayed multiple CpGs per gene: microRNA 886 (MIR886, 10 CpGs),
      phosphodiesterase 4D (PDE4D, 2 CpGs) and tripartite motif-containing 34 (TRIM34,
      2 CpGs). PDE4D was confirmed in both cohorts (p value 2.44e-05). In addition, for
      biomarker construction, we used the penalized logistic regression model,
      resulting in a signature of eight CpGs with an AUC of 0.77. Our findings suggest
      that a distinct level of PD susceptibility stems from individual, epigenetic
      modifications of specific genes. We identified a signature of CpGs in blood cells
      that could separate control from disease with a reasonable discriminatory power,
      holding promise for future epigenetically based biomarker development.

PMID- 27709427
TI  - S-100 Negative Granular Cell Tumor (So-called Primitive Polypoid Non-neural
      Granular Cell Tumor) of the Oral Cavity.
AB  - Four cases of cutaneous S-100 negative granular cell tumor were described in
      1991. Until now, only 3 cases of oral involvement have been documented in English
      literature. Two additional cases of oral S-100 negative granular cell tumor are
      described. Immunohistochemical markers were applied to exclude other lesions that
      may show the presence of granular cells. The clinical findings were correlated
      with the histopathological and immunohistochemical features to arrive at the
      appropriate diagnosis. S-100 negative granular cell tumors are erythematous
      polypoid masses commonly mistaken for granulation tissue or a pyogenic granuloma.
      Any part of the oral cavity may be affected. Histopathologically, the lesions
      consist of sheets, nests, and fascicles of granular cells that are S-100
      negative. The granular cells are non-reactive to SMA, HMB45, Melan A, and CD163.
      The intracytoplasmic granules are diffusely and strongly positive to NKI/C3. The
      cell lineage of the S-100 negative granular cell tumor is obscure. Absence of
      staining with CD163 excludes a histiocytic lineage. Absence of staining with S
      100 excludes a neural origin. Absence of staining with S-100 and key melanoma
      markers HMB45 and Melan A also excludes a melanocytic origin. In this context,
      positive reactivity with NKI/C3 is indicative of presence of intracytoplasmic
      lysosomal granules only. Greater awareness of this lesion in the oral cavity will
      result in better characterization of its biologic potential.

PMID- 27709426
TI  - Diet, gut microbiota and cognition.
AB  - The consumption of a diet high in fat and sugar can lead to the development of
      obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease and cognitive
      decline. In the human gut, the trillions of harmless microorganisms harboured in
      the host's gastrointestinal tract are called the 'gut microbiota'. Consumption of
      a diet high in fat and sugar changes the healthy microbiota composition which
      leads to an imbalanced microbial population in the gut, a phenomenon known as
      "gut dysbiosis". It has been shown that certain types of gut microbiota are
      linked to the pathogenesis of obesity. In addition, long-term consumption of a
      high fat diet is associated with cognitive decline. It has recently been proposed
      that the gut microbiota is part of a mechanistic link between the consumption of
      a high fat diet and the impaired cognition of an individual, termed "microbiota
      gut-brain axis". In this complex relationship between the gut, the brain and the
      gut microbiota, there are several types of gut microbiota and host mechanisms
      involved. Most of these mechanisms are still poorly understood. Therefore, this
      review comprehensively summarizes the current evidence from mainly in vivo
      (rodent and human) studies of the relationship between diet, gut microbiota and
      cognition. The possible mechanisms that the diet and the gut microbiota have on
      cognition are also presented and discussed.

PMID- 27709428
TI  - Intoxication and biochemical responses of freshwater snail Bellamya aeruginosa to
      ethylbenzene.
AB  - No acute toxic data of ethylbenzene on gastropod is available in literature. In
      the present study, the acute toxicity of ethylbenzene was assessed on a
      freshwater snail Bellamya aeruginosa, which was exposed to ethylbenzene
      concentration from 1 to 100 mg/L for 96 h. No mortality occurred, but a
      manifestation of intoxication (distress syndrome) was observed in part of exposed
      snails, and meanwhile, another part was moved normally. The distress syndrome
      showed clear dose- and time-dependent effects, and the 96-h EC50 value for
      distress syndrome was 13.3 mg/L in snail. The biochemical responses induced by
      ethylbenzene to the snail, including acetylcholinesterase (AChE) in the whole
      body and superoxide dismutase (SOD), catalase (CAT), glutathione S-transferases
      (GST), and reduced glutathione (GSH) in the hepatopancreas, were evaluated both
      for distressed snail and moved snail. The AChE activity of distressed snail was
      all inhibited more than 45 %, and the inhibition of AChE activity in the moved
      snail was all less than 30 % and more than 20 %, demonstrating that ethylbenzene
      exerted nervous toxicity to both distressed snail and moved snail. Meanwhile, the
      difference for AChE activity between the two different response snails was
      significant. Among the antioxidant biomarkers (SOD, CAT, GST, and GSH), only GST
      displayed significant difference between the distressed snail and moved snail.
      However, the activities of enzymes (SOD, CAT, and GST) in the moved snail were
      greater than those in the distressed snail, no matter significantly or
      insignificantly, which indicated that the ability of antioxidant defense in the
      distressed snail was weaker than that in the moved snail. The findings here
      reported manifest that ethylbenzene exerted nervous toxicity to snail, and the
      snail with intoxication response (distress syndrome) presented larger inhibition
      on AChE activity and weaker antioxidant ability in comparison with the moved
      snail.

PMID- 27709430
TI  - Bioaccumulation of natural radionuclides in molluscs from the Ebro Delta area.
AB  - 210Po, 210Pb, 234U, 238U, 232Th and 230Th were analysed in the edible part of
      four different species of bivalves typically produced and consumed in the Ebro
      Delta area. The results show that the main contributor to the radioactive content
      in these species was 210Po, with values ranging between 263.1 +/- 26.6 and 813.0
      +/- 72.9 Bq/kg (d.w.), which are higher than the usual reported activity levels
      in other geographical areas. This can probably be attributed to the activities of
      a phosphate industrial plant located upstream on the Ebro River, which may lead
      to enhanced levels of naturally occurring radioactive isotopes in the aquatic
      ecosystem. To determine the possible impact on health, the committed effective
      doses through the consumption of the different species were evaluated and the
      cumulative total annual effective dose for their consumption was estimated to
      187.6 MUSv/year, which is in the range of 200-1000 MUSv/year given by UNSCEAR.

PMID- 27709429
TI  - Nutrient changes and biodynamics of Eisenia fetida during vermicomposting of
      water lettuce (Pistia sp.) biomass: a noxious weed of aquatic system.
AB  - This paper reports the results of vermicomposting of water lettuce biomass (WL)
      spiked with cow dung at ratios of 20, 40, 60, and 80 % employing Eisenia fetida.
      A total of four treatments were established and changes in chemical properties of
      mixtures were observed. Vermicomposting caused a decrease in pH, TOC, volatile
      solids, and C/N ratio by 1.01-1.08-fold, 0.85-0.92-fold, 0.94-0.96-fold, 0.56
      0.70-fold, respectively, but increase in EC, totN, totP, totK, totCa, totZn,
      totFe, and totCu, by 1.19-1.42-fold, 1.33-1.68-fold, 1.38-1.69-fold, 1.13-1.24
      fold, 1.04-1.11-fold, 1.16-1.37-fold, 1.05-1.113-fold, 1.10-1.27-fold,
      respectively. Overall, the treatment with 60-80 % of WL showed the maximum
      decomposition and mineralization rates. The earthworm showed the growth and
      reproduction rate in considerable ranges in all treatment setups but setups with
      60-80 % WL proportion exhibited the optimum results. Results reveal that biomass
      of water lettuce can be utilized effectively for production of valuable manure
      through vermicomposting system.

PMID- 27709431
TI  - Endosulfan inducing apoptosis and necroptosis through activation RIPK signaling
      pathway in human umbilical vascular endothelial cells.
AB  - Endosulfan, an organochlorine pesticide, was found in human blood, and its
      possible cardiovascular toxicity has been suggested. However, the mechanism about
      endothelial cell injuries induced by endosulfan has remained unknown. In the
      present study, human umbilical vein endothelial cells (HUVECs) were chosen to
      explore the toxicity mechanism and were treated with 0, 1, 6, and 12 MUg/mL-1
      endosulfan for 24 h, respectively. The results showed that exposure to endosulfan
      could inhibit the cell viability, increase the release of lactate dehydrogenase
      (LDH), damage the ultrastructure, and lead to apoptosis and necroptosis in
      HUVECs. Furthermore, endosulfan upregulated the expressions of receptor
      interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3
      (RIPK3), mixed lineage kinase domain-like (MLKL), caspase 8, and caspase 3, which
      means the activation of RIPK1 pathways. In addition, endosulfan promoted the
      increases of ROS, IL-1alpha, and IL-33 levels while antioxidant N-acetyl-L
      cysteine (NAC) effectively attenuated the cytotoxicity from endosulfan. Taken
      together, these results have demonstrated that endosulfan induces the apoptosis
      and necroptosis of HUVECs, where the RIPK pathway plays a pro-necroptotic role
      and NAC plays an anti-necroptotic role. Our results may contribute to
      understanding cellular mechanisms for endosulfan-induced cardiovascular toxicity.

PMID- 27709432
TI  - Effects of CeO2, CuO, and ZnO nanoparticles on physiological features of
      Microcystis aeruginosa and the production and composition of extracellular
      polymeric substances.
AB  - Extracellular polymeric substances (EPS) are key components of the cyanobacterium
      Microcystis aeruginosa and play an important role in cyanobacteria blooms
      formation. Here, we analyzed the effects of 48-h exposure to nanosized CeO2 (n
      CeO2), CuO (n-CuO), and ZnO (n-ZnO) on the production and composition of EPS of
      M. aeruginosa. Toxicity experiments revealed that soluble nanoparticles (NPs) (n
      ZnO, n-CuO) demonstrated higher toxicity to cells and caused membrane damage. The
      production of LB-EPS increased by 34.48, 20.09, and 46.33 %, and TB-EPS increased
      by -5.78, 22.3, and -2.67 % in the presence of n-CeO2, n-CuO, and n-ZnO NPs,
      respectively, and polysaccharides are the main incremental portion compared with
      protein and humic acids. Three-dimensional excitation-emission fluorescence
      spectra revealed the enhancement of fulvic-humic-like and disappearance of
      tyrosine aromatic substances in TB-EPS compared with the slight changes observed
      in LB-EPS. Fourier-transform infrared spectroscopy illustrated the susceptibility
      of -NH2 and double-bonded carbon and oxygen in amides to three types of NPs.
      These results improve our understanding of the potential influence of NPs on the
      aggregation behaviors of cyanobacteria and formation process of cyanobacteria
      blooms. Graphical abstract ?.

PMID- 27709433
TI  - Risk assessment of maize damage by wireworms (Coleoptera: Elateridae) as the
      first step in implementing IPM and in reducing the environmental impact of soil
      insecticides.
AB  - A survey of maize fields was conducted in northeast Italy from 1986 to 2014,
      resulting in a dataset of 1296 records including information on wireworm damage
      to maize, plant-attacking species, agronomic characteristics, landscape and
      climate. Three wireworm species, Agriotes brevis Candeze, A. sordidus Illiger and
      A. ustulatus Schaller, were identified as the dominant pest species in maize
      fields. Over the 29-year period surveyed, no yield reduction was observed when
      wireworm plant damage was below 15 % of the stand. A preliminary univariate
      analysis of risk assessment was applied to identify the main factors influencing
      the occurrence of damage. A multifactorial model was then applied by using the
      significant factors identified. This model allowed the research to highlight the
      strongest factors and to analyse how the main factors together influenced damage
      risk. The strongest factors were: A. brevis as prevalent damaging species, soil
      organic matter content >5 %, rotation including meadows and/or double crops, A.
      sordidus as prevalent damaging species, and surrounding landscape mainly meadows,
      uncultivated grass and double crops. The multifactorial model also showed how the
      simultaneous occurrence of two or more of the aforementioned risk factors can
      conspicuously increase the risk of wireworm damage to maize crops, while the
      probability of damage to a field with no-risk factors is always low (<1 %). These
      results make it possible to draw risk maps to identify low-risk and high-risk
      areas, a first step in implementing bespoke IPM procedures in an attempt to
      reduce the impact of soil insecticides significantly.

PMID- 27709434
TI  - Complete adherence to evidence-based quality-of-care indicators for
      Staphylococcus aureus bacteremia resulted in better prognosis.
AB  - PURPOSE: Staphylococcus aureus bacteremia (SAB) is a serious clinical condition
      associated with high morbidity and mortality. Recent studies have revealed that
      adherence to evidence-based quality-of-care indicators (QCIs) for the management
      of SAB could result in reduced mortality. We aimed to determine whether
      compliance with QCIs was associated with mortality and whether compliance with
      QCIs predicted the mortality of patients with SAB. METHODS: In a university
      hospital in Kyoto, Japan, SAB patients, who survived at least 14 days after
      positive blood cultures were analyzed from 2006 to 2014 to assess their
      compliance with QCIs and the trend in mortality. In addition, the predicted
      mortality, which was stratified by the number of fulfilled QCIs (QCI points), was
      calculated. In this study, the following five main QCI points were evaluated: (1)
      follow-up blood cultures; (2) early source control when applicable; (3)
      echocardiography; (4) the early use of appropriate antibiotics, and (5) the
      appropriate duration of therapy. RESULTS: We identified 477 eligible SAB cases,
      of which 199 were MRSA cases (41.7 %). The proportion of SAB cases in which the
      physicians adhered to at least four QCIs increased gradually from 47.5 % in 2006
      to 79.3 % in 2014 (P = 0.001); whereas, the 30-day mortality decreased from 10.0
      to 3.4 % after treatment completion. CONCLUSIONS: With an increase in the
      proportion of SAB cases adhering to QCIs, better prognoses were observed for
      patients with SAB. The QCI points reflected the 30-day mortality.

PMID- 27709435
TI  - Virological Quality of Irrigation Water in Leafy Green Vegetables and Berry
      Fruits Production Chains.
AB  - This study condenses data acquired during investigations of the virological
      quality of irrigation water used in production of fresh produce. One hundred and
      eight samples of irrigation water were collected from five berry fruit farms in
      Finland (1), the Czech Republic (1), Serbia (2), and Poland (1), and sixty-one
      samples were collected from three leafy green vegetable farms in Poland, Serbia,
      and Greece. Samples were analyzed for index viruses of human or animal fecal
      contamination (human and porcine adenoviruses, and bovine polyoma viruses), and
      human pathogenic viruses (hepatitis A virus, hepatitis E virus, and noroviruses
      GI/GII). Both index and pathogenic viruses were found in irrigation water samples
      from the leafy green vegetables production chain. The data on the presence of
      index viruses indicated that the highest percentage of fecal contamination was of
      human origin (28.1 %, 18/64), followed by that of porcine (15.4 %, 6/39) and
      bovine (5.1 %, 2/39) origins. Hepatitis E virus (5 %, 1/20) and noroviruses GII
      (14.3 %, 4/28) were also detected. Samples from berry fruit production were also
      positive for both index and pathogenic viruses. The highest percentage of fecal
      contamination was of human origin (8.3 %, 9/108), followed by that of porcine,
      4.5 % (4/89) and bovine, 1.1 % (1/89) origins. Norovirus GII (3.6 %, 2/56) was
      also detected. These data demonstrate that irrigation water used in primary
      production is an important vehicle of viral contamination for fresh produce, and
      thus is a critical control point which should be integrated into food safety
      management systems for viruses. The recommendations of Codex Alimentarius, as
      well as regulations on the use of water of appropriate quality for irrigation
      purposes, should be followed.

PMID- 27709436
TI  - Rapid and Sensitive Detection of Lymphocystis Disease Virus Genotype VII by Loop
      Mediated Isothermal Amplification.
AB  - Lymphocystis disease virus (LCDV) infections have been described in gilthead
      seabream (Sparus aurata L.) and Senegalese sole (Solea senegalensis, Kaup), two
      of the most important marine fish species in the Mediterranean aquaculture. In
      this study, a rapid, specific, and sensitive detection method for LCDV genotype
      VII based on loop-mediated isothermal amplification (LAMP) was developed. The
      LAMP assay, performed using an apparatus with real-time amplification monitoring,
      was able to specifically detect LCDV genotype VII from clinically positive
      samples in less than 12 min. In addition, the assay allowed the detection of LCDV
      in all asymptomatic carrier fish analysed, identified by qPCR, showing an
      analytical sensitivity of ten copies of viral DNA per reaction. The LCDV LAMP
      assay has proven to be a promising diagnostic method that can be used easily in
      fish farms to detect the presence and spread of this iridovirus.

PMID- 27709438
TI  - 3D structure prediction of histone acetyltransferase proteins of the MYST family
      and their interactome in Arabidopsis thaliana.
AB  - Histone lysine acetylation is a reversible post-translational modification that
      does not involve changes in DNA sequences. Enzymes play an important role in
      developmental processes and their deregulation has been linked to the progression
      of diverse disorders. The HAT enzyme family fulfills an important role in various
      developmental processes mediated by the state of chromatin, and have been
      attributed to its deregulation. To understand acetylation mechanisms and their
      role in cell signaling, transcriptional regulation, and apoptosis, it is crucial
      to identify and analyze acetylation sites. Bioinformatics methods can be used to
      generate relatively precise predictions. Here we applied classical bioinformatics
      methods-sequence alignment, homology modeling, and docking-to compare approved
      and predicted lysine acetylation processes in different organisms. HAM1 and HAM2
      are analogs of KAT8 and KAT7 (MYST1 and MYST2), members of the MYST histone
      acetyltransferase family, and our results show that HAM1 and HAM2 have much in
      common with other representatives of MYST families from various organisms. One
      function of acetyl-CoA binding was predicted with a high level of probability by
      computational methods. Based on our data, we conclude that, despite huge genetic
      distances and some structural differences between animal and plant species, a
      closer look at acetylation mechanism shows that they have much in common.

PMID- 27709439
TI  - Theoretical studies on the hydrogen-bonding interactions between luteolin and
      water: a DFT approach.
AB  - Flavonoids are among the most important bioactive compounds responsible for the
      medical properties of honey and propolis. Water is the solvent most commonly used
      to extract flavonoids from honey and propolis. Hydrogen-bonding interactions are
      of great importance in the extraction process. In this work, hydrogen-bonding
      interactions between a representative flavonoid, luteolin, and water were
      investigated by density functional theory (DFT) from a theoretical viewpoint. The
      following conclusions were drawn: first, the molecular structure of luteolin is
      non-planar. Second, nine optimized geometries for the luteolin-H2O complex were
      obtained. With the exception of the aromatic hydrogen atoms in the phenyl
      substituent, the other hydrogen and oxygen atoms formed hydrogen-bonds with H2O.
      Third, luteolin-H2O complexation is accompanied by charge rearrangement. The
      electron density and the second-order perturbation stabilization energy [E(2)] in
      the related anti-bonding orbital of the hydrogen-bond donors were increased,
      causing elongation and a red-shift of the X-H bond in X-H...Y. The stronger
      interaction makes the electron density and the E(2) increase more in the more
      stable geometries. The sum of the electron density is transferred from hydrogen
      bond acceptors to donors. Fourth, the hydrogen-bonds in the luteolin-H2O complex
      are weak and basically electrostatic in nature. In addition, O-H...O hydrogen
      bonds are stronger than C-H...O hydrogen-bonds in the luteolin-H2O complex.

PMID- 27709437
TI  - Insomnia in probable migraine: a population-based study.
AB  - BACKGROUND: Insomnia is a common complaint among individuals with migraine. The
      close association between insomnia and migraine has been reported in clinic-based
      and population-based studies. Probable migraine (PM) is a migrainous headache
      which fulfills all but one criterion in the migraine diagnostic criteria.
      However, an association between insomnia and PM has rarely been reported. This
      study is to investigate the association between insomnia and PM in comparison
      with migraine using data from the Korean Headache-Sleep Study. METHODS: The
      Korean Headache-Sleep Study is a nation-wide cross-sectional survey for all
      Korean adults aged 19-69 years. The survey was performed via face-to-face
      interview using a questionnaire on sleep and headache. If an individual's
      Insomnia Severity Index score was >=15.5, she/he was diagnosed as having
      insomnia. RESULTS: Of 2695 participants, the prevalence of migraine, PM and
      insomnia was 5.3, 14.1 and 3.6 %, respectively. The prevalence of insomnia among
      subjects with PM was not significantly different compared to those with migraine
      (8.2 % vs. 9.1 %, p = 0.860). However, insomnia prevalence in subjects with PM
      was significantly higher than in non-headache controls (8.2 % vs. 1.8 %, p <
      0.001). Insomnia Severity Index score was significantly higher in subjects with
      migraine compared to those with PM (6.8 +/- 5.8 vs. 5.5 +/- 5.8, p = 0.012).
      Headache frequency and Headache Impact Test-6 score were significantly higher in
      subjects with migraine and PM with insomnia compared to those without insomnia.
      Multivariable linear analyses showed that anxiety, depression, headache frequency
      and headache intensity were independent variables for contributing the ISI score
      among subjects with PM. CONCLUSIONS: The prevalence of insomnia among subjects
      with PM was not significantly different compared to those with migraine. Anxiety,
      depression, headache frequency and headache intensity were related with ISI score
      in subjects with PM.

PMID- 27709440
TI  - Protein remains stable at unusually high temperatures when solvated in aqueous
      mixtures of amino acid based ionic liquids.
AB  - Using molecular dynamics simulations, we investigated the thermal stability and
      real-time denaturation of a model mini-protein in four solvents: (1) water, (2) 1
      ethyl-3-methylimidazolium alaninate [EMIM][ALA] (5 mol% in water), (3)
      methioninate [EMIM][MET] (5 mol% in water), and (4) tryptophanate [EMIM][TRP] (5
      mol% in water). Upon analyzing the radius of gyration, the solvent-accessible
      surface area, root-mean-squared deviations, and inter- and intramolecular
      hydrogen bonds, we found that the mini-protein remains stable at 30-40 K higher
      temperatures in aqueous amino acid based ionic liquids (AAILs) than in water.
      This thermal stability was correlated with the thermodynamics and shear viscosity
      of the AAIL-containing mixtures. These results suggest that AAILs are generally
      favorable for protein conservation. Graphical Abstract Conformation of the [TRP]
      cage mini-protein in an aqueous amino acid based ionic liquid (AAIL).

PMID- 27709441
TI  - Correlation Between Intraocular Pressure and Central Corneal Thickness in Persian
      Children.
AB  - INTRODUCTION: This study aimed to determine intraocular pressure (IOP) and
      central corneal thickness (CCT) measurements in healthy Persian children to find
      clinical reference values in this ethnicity. Additionally, we examined the
      possible relationship between these measurements. METHODS: This cross-sectional
      study included 262 eyes of 131 Persian primary school children between 6 and 13
      years of age. All eyes were healthy and had no anterior or posterior segment
      abnormalities, corneal disease, or evidence of glaucoma. Specular microscopy was
      used to measure CCT and both noncontact tonometry (NCT) and Goldmann applanation
      tonometer (GAT) were used to measure IOP. Correlations between IOP measurements
      were also examined. RESULTS: Mean CCT was 513.47 +/- 34.51 MUm in the right eye
      (OD) and 513.93 +/- 33.88 MUm in the left eye (OS). The CCT was not significantly
      different between older (10-13 years) and younger (6-9 years) patients. Mean IOP
      measured with GAT was 13.86 +/- 2.13 mmHg OD and 13.72 +/- 2.04 mmHg OS and mean
      IOP measured with NCT was 15.26 +/- 2.38 mmHg OD and 15.11 +/- 2.18 mmHg OS. The
      IOP and CCT measured with GAT were weakly correlated (OD: r = 0.141, P = 0.114;
      OS: r = 0.236, P = 0.007). However, IOP and CCT measured with NCT (OD: r = 0.487,
      P = 0.000; OS: r = 0.456, P = 0.000) were moderately correlated. Our outcomes
      demonstrated that for 100 MUm increase in CCT, IOP measured with GAT and NCT
      increased by 0.8 and 3.3 mmHg, respectively, in OD and by 1.4 and 2.9 mmHg in OS.
      Based on intraclass correlation coefficients, IOP measurements made with GAT and
      NCT were in fair agreement in OD and in good agreement in OS. CONCLUSION: The IOP
      and CCT in healthy Persian school children (6-13 years old) were positively
      correlated. Our findings revealed that corneal thickness is thinner in Persian
      children than in most other racial groups. FUNDING: This study has been funded by
      deputy dean in research of School of Medicine and deputy vice chancellor of
      Shiraz University of Medical Sciences, Shiraz, Iran.

PMID- 27709442
TI  - Memory strategy use in older adults with subjective memory complaints.
AB  - BACKGROUND: Subjective memory complaints (SMC) are common among older adults, but
      it is unclear to what extent adults with SMC spontaneously use memory strategies
      to compensate for their memory problems. As SMC may be a risk factor for memory
      decline later, it is important to extend our knowledge about spontaneous
      compensatory mechanisms in older adults with SMC. METHOD: Self-reported strategy
      use and observed strategy use were assessed in 38 adults with and 38 without SMC.
      RESULTS: Adults with SMC used more strategies in daily life than those without.
      In the SMC group, memory complaints were positively correlated with strategy use.
      Only in adults without SMC, a significant correlation was found between observed
      strategy use and task performance. CONCLUSION: Strategy use in older adults with
      SMC may be compensatory in nature, but did not increase their objective memory
      performance. Therefore, older adults with SMC might benefit from interventions
      aimed at optimizing strategy use.

PMID- 27709443
TI  - Safety and efficacy of etanercept and adalimumab in children aged 2 to 4 years
      with juvenile idiopathic arthritis.
AB  - The TNF inhibitors etanercept (ETA) and adalimumab (ADA) are approved for
      treating patients older than 2 years with polyarticular juvenile idiopathic
      arthritis (JIA). Because long-term experience of treating children younger than 4
      years is limited, we evaluated the efficacy and safety of ETA or ADA in patients
      aged 2-4 years. This prospective, long-term, observational registry study
      documented baseline demographics, clinical characteristics, disease activity
      parameters, and safety of patients treated with ETA or ADA. Efficacy was
      determined using the JADAS-10, the JADAS criteria for minimal disease activity
      (MDA) and remission, and the PedACR response criteria after 3, 6, 12, 18, and 24
      months. Between January 2001 and March 2015, 85 patients with polyarticular JIA
      aged 2-4 years started anti-TNF-alpha treatment. Seventy-four (54 girls) patients
      were treated with ETA and 11 (7 girls) with ADA. After 6/12/24 months of
      treatment, JADAS-MDA was reached by 55/58/58 % of ETA patients and 50/71/66 % of
      ADA patients. Furthermore, JADAS-Remission was achieved by 35/44/50 % of ETA
      patients and 16/28/66 % of ADA patients. PedACR 50/70/90 response was achieved by
      64/54/41 % of ETA patients and 56/33/22 % of ADA patients at the last treatment
      observation. Discontinuation because of remission or inefficacy was recorded in
      24 (29 %) and 28 (33 %) patients, respectively. Seventy-nine adverse events and
      four serious adverse events were reported. Administration of ETA and ADA in JIA
      patients younger than 4 years was efficacious, well tolerated, and safe. Patients
      younger than 4 years may show marked improvement following anti-TNF-alpha
      therapy.

PMID- 27709445
TI  - Childhood polyarteritis nodosa: diagnosis with non-invasive imaging techniques.
AB  - There is limited number of publications about the use of non-invasive imaging
      modalities in the diagnosis of childhood polyarteritis nodosa (cPAN). The aim of
      this study was to present the clinical and imaging findings of the patients with
      cPAN who were diagnosed with non-invasive imaging techniques. Files of patients
      who had been diagnosed as cPAN in our department from 2005 to 2015 were reviewed,
      retrospectively. Demographic, clinical, laboratory, and imaging findings of the
      patients were evaluated. Nine patients (8M, 1F; age at disease onset: 12.5 years
      (7-16)) had been diagnosed as cPAN in our clinic with non-invasive imaging
      techniques within the last 10 years. Abdominal pain, fever, fatigue, and myalgia
      were the most frequent complaints. Doppler ultrasonography (US) was used in the
      diagnosis of seven patients and computed tomography (CT) angiography was done in
      four patients. Duration between admission to our center and diagnosis was median
      of 5 days (8 h-10 days), including four patients who were diagnosed within 24 h
      of admission. Approximately 80 % of our patients with cPAN had MEFV gene
      mutations and 90 % had elevated anti-streptolysin O levels. All of them had the
      involvement of the gastrointestinal tract. Hepatic and cystic arterial
      involvements were detected in seven and six patients, respectively. This report
      included the largest cPAN series that were diagnosed with non-invasive imaging
      modalities. We suggest that non-invasive modalities, especially Doppler US,
      should be considered in first line approach in the diagnosis of these patients,
      particularly in children.

PMID- 27709444
TI  - The usage of biological DMARDs and clinical remission of rheumatoid arthritis in
      China: a real-world large scale study.
AB  - The aims of this study are to characterize the biological disease-modifying
      antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission
      rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical
      practice in China. Consenting RA patients (>=18 years) from 15 teaching hospitals
      and receiving marketed bDMARDs were included. In total, 802 patients (81.3 %
      women, 49.0 +/- 13.9 years) were included; 89.5 % were receiving a combination of
      bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were
      receiving bDMARD monotherapy. Etanercept (including Enbrel(r) and local brand Yi
      Sai Pu(r) and Qiangke(r)), tocilizumab, adalimumab, and infliximab were used by
      66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a
      mean weekly dose of 38.2 +/- 15.6 mg for 25.5 +/- 47.0 weeks and tocilizumab at
      94.5 +/- 21.9 mg for 4.7 +/- 7.5 weeks. Overall rate of remission was 12.6 %, 5.4
      % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with
      patients receiving bDMARDs for <3 months, those receiving bDMARDs for >=3 months
      exhibited significantly lower DAS28 scores (p < 0.0001), and a significantly
      higher proportion of patients who received bDMARDs for >=12 months achieved the
      treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p <
      0.0001). Patients receiving combination therapy with csDMARDs exhibited lower
      DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011).
      This large-scale real-world study showed that bDMARD usage patterns in routine
      clinical practice in China were in accordance with international guidelines for
      RA management despite the short treatment duration. Longer duration of bDMARD
      usage and combination therapy showed a favored outcome of RA.

PMID- 27709446
TI  - Triple-loop reentrant atrial tachycardia originated after pulmonary vein
      isolation.

PMID- 27709449
TI  - Human chorionic gonadotropin (hCG) concentrations during the late first trimester
      are associated with fetal growth in a fetal sex-specific manner.
AB  - Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates
      placental development. hCG concentrations vary widely throughout gestation and
      differ based on fetal sex. Abnormal hCG concentrations are associated with
      adverse pregnancy outcomes including fetal growth restriction. We studied the
      association of hCG concentrations with fetal growth and birth weight. In
      addition, we investigated effect modification by gestational age of hCG
      measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1
      26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and
      >25th weeks) and birth weight were measured in 7987 mother-child pairs from the
      Generation R cohort and used to establish fetal growth. Small for gestational age
      (SGA) was defined as a standardized birth weight lower than the 10th percentile
      of the study population. There was a non-linear association of hCG with birth
      weight (P = 0.009). However, only low hCG concentrations measured during the late
      first trimester (11th and 12th week) were associated with birth weight and SGA.
      Low hCG concentrations measured in the late first trimester were also associated
      with decreased fetal growth (P = 0.0002). This was the case for both male and
      female fetuses. In contrast, high hCG concentrations during the late first
      trimester were associated with increased fetal growth amongst female, but not
      male fetuses. Low hCG in the late first trimester is associated with lower birth
      weight due to a decrease in fetal growth. Fetal sex differences exist in the
      association of hCG concentrations with fetal growth.

PMID- 27709447
TI  - Current views on HIV-1 latency, persistence, and cure.
AB  - HIV-1 infection cannot be cured as it persists in latently infected cells that
      are targeted neither by the immune system nor by available therapeutic
      approaches. Consequently, a lifelong therapy suppressing only the actively
      replicating virus is necessary. The latent reservoir has been defined and
      characterized in various experimental models and in human patients, allowing
      research and development of approaches targeting individual steps critical for
      HIV-1 latency establishment, maintenance, and reactivation. However, additional
      mechanisms and processes driving the remaining low-level HIV-1 replication in the
      presence of the suppressive therapy still remain to be identified and targeted.
      Current approaches toward HIV-1 cure involve namely attempts to reactivate and
      purge HIV latently infected cells (so-called "shock and kill" strategy), as well
      as approaches involving gene therapy and/or gene editing and stem cell
      transplantation aiming at generation of cells resistant to HIV-1. This review
      summarizes current views and concepts underlying different approaches aiming at
      functional or sterilizing cure of HIV-1 infection.

PMID- 27709451
TI  - Successful early romiplostim use in a case of severe immune thrombocytopenia with
      critical carotid arterial injury.
AB  - Thrombopoietin receptor (TPO-R) agonists have been shown to be effective in
      refractory chronic immune thrombocytopenia (ITP); however, their efficacy in
      patients under critical care is not known. We report the case of a female patient
      with a newly diagnosed ITP who experienced severe bleeding from an external
      wound. The patient was administered the standard treatments for ITP, which are
      high-dose intravenous immunoglobulin (IVIg) and corticosteroids. However,
      following failure of these treatments, we administered romiplostim on day 6 after
      the onset of ITP. On day 6 after the initiation of romiplostim, there was
      improvement in platelet count and bleeding tendency. We were subsequently able to
      perform a splenectomy successfully. The efficacy of TPO-R agonists in ITP has
      been reported in several situations, including before surgery in an ITP patient;
      however, the use of TPO-R for arterial bleeding with shock has not been reported.
      To our knowledge, the present article is a rare case report of the use of a TPO-R
      agonist in a patient with critical artery injury. Our data suggest that the early
      use of romiplostim is effective in emergency cases of newly diagnosed ITP with
      life-threatening bleeding, which is refractory to standard treatment.

PMID- 27709448
TI  - A pooled analysis of the association of isolated low levels of high-density
      lipoprotein cholesterol with cardiovascular mortality in Japan.
AB  - Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown
      to be associated with increased risk of coronary heart disease (CHD). However,
      because this is usually observed in the context of other lipid abnormalities, it
      is not known whether isolated low serum HDL-C levels are an independent risk
      factor for CHD. We performed a large pooled analysis in Japan using data from
      nine cohorts with 41,206 participants aged 40-89 years who were free of
      cardiovascular disease at baseline. We divided participants into three groups:
      isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified
      Cox proportional hazards models were used to estimate multivariate-adjusted
      hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial
      cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138
      deaths, respectively, in these groups. Non-isolated low HDL-C was significantly
      associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 %
      confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not.
      Although isolated low HDL-C was significantly associated with decreased risk of
      CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with
      increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62,
      95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion,
      isolated low HDL-C levels are not associated with increased risk of CHD in Japan.
      CHD risk may, therefore, be more strongly affected by serum total cholesterol
      levels in this population.

PMID- 27709450
TI  - Analysis of allogeneic hematopoietic stem cell transplantation with high-dose
      cyclophosphamide-induced immune tolerance for severe aplastic anemia.
AB  - The study was aimed to explore the efficacy and safety of allo-HSCT with high
      dose cyclophosphamide-induced immune tolerance for SAA. In the present study, 20
      cases (12 male, 8 female; average age = 17.8 years) received reduced-intensity
      conditioning allo-HSCT from August 2012 to August 2014 in the Beijing Military
      Region General Hospital. All were HLA mismatched and received CSA; 11 received
      ATG-intensive immune therapy. Donors underwent mobilization with cell colony
      stimulating factor. The modified preconditioning regimen included reduced
      strength fludarabine combined with Busulfex and cytarabine, cyclophosphamide.
      Cyclophosphamide (50 mg/kg/d) induced immune tolerance 3 days after
      transplantation and was combined with immunosuppressive agents, including CSA,
      MTX, and FK506, for GVHD prophylaxis and the management of observed toxicity,
      GVHD and DFS. Hematopoietic reconstitution was achieved in 17 cases and
      engraftment after a second transplantation in an additional three cases. The
      average times to engraftment were 17.4 and 21.3 days, respectively, with
      neutrophils >=0.5 * 109/L and platelets >=20 * 109/L. Engraftment was confirmed
      by the evidence of 100 % donor hematopoiesis; T lymphocyte subset counts also
      increased significantly after transplantation. During follow-up monitoring to
      April 2015 (median duration = 17.7 months), three patients died of complications,
      while the other 17 showed disease-free survival (DFS rate = 85 %; longest DFS
      period = 32 months). Reduced-intensity allo-HSCT with high-dose cyclophosphamide
      induced immune tolerance treatment is effective for SAA and can be the key
      technology extensively used in clinic, but its efficacy needs to be confirmed
      further with prospective randomized study with increased sample size.

PMID- 27709452
TI  - Statistical Approaches to Assess Biosimilarity from Analytical Data.
AB  - Protein therapeutics have unique critical quality attributes (CQAs) that define
      their purity, potency, and safety. The analytical methods used to assess CQAs
      must be able to distinguish clinically meaningful differences in comparator
      products, and the most important CQAs should be evaluated with the most
      statistical rigor. High-risk CQA measurements assess the most important
      attributes that directly impact the clinical mechanism of action or have known
      implications for safety, while the moderate- to low-risk characteristics may have
      a lower direct impact and thereby may have a broader range to establish
      similarity. Statistical equivalence testing is applied for high-risk CQA
      measurements to establish the degree of similarity (e.g., highly similar
      fingerprint, highly similar, or similar) of selected attributes. Notably, some
      high-risk CQAs (e.g., primary sequence or disulfide bonding) are qualitative
      (e.g., the same as the originator or not the same) and therefore not amenable to
      equivalence testing. For biosimilars, an important step is the acquisition of a
      sufficient number of unique originator drug product lots to measure the
      variability in the originator drug manufacturing process and provide sufficient
      statistical power for the analytical data comparisons. Together, these analytical
      evaluations, along with PK/PD and safety data (immunogenicity), provide the data
      necessary to determine if the totality of the evidence warrants a designation of
      biosimilarity and subsequent licensure for marketing in the USA. In this paper, a
      case study approach is used to provide examples of analytical similarity
      exercises and the appropriateness of statistical approaches for the example data.

PMID- 27709453
TI  - Commentary on "Statistical Approaches to Assess Biosimilarity from Analytical
      Data" by Burdick et al [1].

PMID- 27709454
TI  - Death with dignity from the Confucian perspective.
AB  - Death with dignity is a significant issue in modern bioethics. In modern
      healthcare, the wide use of new technologies at the end of life has caused heated
      debate on how to protect human dignity. The key point of contention lies in the
      different understandings of human dignity and the dignity of death. Human dignity
      has never been a clear concept in Western ethical explorations, and the dignity
      of death has given rise to more confusions. Although there is no such term as
      "dignity" in Confucian ethics, there are discussions of a number of ideas related
      to human dignity and the dignity of death. Therefore, Confucian bioethics can
      offer a new perspective for understanding the theoretical difficulties associated
      with the dignity of death and new methods for solving them. In this article, we
      attempt to reconstruct Confucian views on human dignity and the dignity of death
      and, based on those views, to analyze the following issues: the relationship
      between the dignity of death and biological life, the relationship between the
      dignity of death and suffering, the relationship between the dignity of death and
      the autonomy of human beings, and the relationship between the dignity of death
      and social justice. This article will also compare the Confucian views on these
      issues with the views of Western philosophers. Confucian ethics can offer
      distinct answers to the above issues and help resolve some confusions concerning
      concepts and theories in Western research on the dignity of death.

PMID- 27709455
TI  - Composing Disability: Diagnosis, Interrupted.
AB  - Writing is central both to the medical diagnostic codification of disability and
      to disabled people's efforts to interrupt, complicate, or disrupt dominant
      medical narratives. This Symposium, like the George Washington University
      conference from which it takes its name, creates space for diverse modes and
      genres of claiming authority regarding diagnosis and its cultural and material
      effects. "Queer" and "crip" interrogations of diagnosis illuminate its status as
      a cultural phenomenon, embracing culturally disavowed embodiments and embodied
      experiences as tools for diagnosing inegalitarian social relations and
      opportunities for cultural interventions. This Symposium traces the workings of
      diagnostic normativity manifested in experiences such as "disruptive deafness,"
      unstable bodily materialities, pathologized grief and other forms of affective
      distress, and "surgical assemblages." It presents a diverse array of
      compositions, articulated on each writer's own terms, addressing a range of
      embodied experiences through multiple genres and voices, ranging from
      conversation transcript to scholarly essay, poetry, graphic memoir, and personal
      essay. Here, laypersons interrupt monologic medical diagnosis, claiming space to
      compose themselves. Together, the authors trace instances of corporeal
      "correction" back to the noxious agents, both environmental and political, that
      consistently breach the boundaries of corporeality.

PMID- 27709456
TI  - Leveraging Partnerships: Families, Schools, and Providers Working Together to
      Improve Asthma Management.
AB  - Asthma is one of the most common illnesses of school-aged children and can lead
      to both health and educational disparities. Children from low socioeconomic
      backgrounds and racial/ethnic minorities suffer the greatest impact. They often
      lack the asthma self-management skills to successfully monitor, navigate, and
      negotiate appropriate asthma care. School settings are a strategic point of
      contact for this additional support. School nurses can monitor for signs of
      asthma worsening, manage symptoms, provide care coordination, and reinforce self
      management skills. Likewise, school-based asthma programs have the potential to
      reduce health and educational disparities, but it is the strong linkage to the
      asthma care provider that is critical to successful school-based asthma
      management. Healthcare providers are encouraged to establish partnerships with
      families through patient-centered care and schools through clear communication
      and care coordination to ensure asthma is well controlled so the child is in
      school and ready to learn.

PMID- 27709458
TI  - Retraction Note to: Effect of coupling asynchronous acoustoelectric effects on
      the corrosion behavior, microhardness and biocompatibility of biomedical titanium
      alloy strips.

PMID- 27709459
TI  - Novel carboxymethyl chitosan-graphene oxide hybrid particles for drug delivery.
AB  - We describe an electrostatic droplet generation method to prepare a novel
      carboxymethyl chitosan-graphene oxide hybrid particles for delivery purpose.
      Under an adjustable electrostatic field, graphene oxide and carboxymethyl
      chitosan mixed solution was sprayed as uniform micro-droplets, which were
      solidified as particles in CaCl2 solution. Such hybrid particles are wished to
      have excellent stability in saline solution, and better delivery properties than
      pristine carboxymethyl chitosan particles. The effects of micro-droplets
      generation conditions on particles formation were systematically investigated. At
      conditions of 40 mg/ml of carboxymethyl chitosan, 2 mg/ml of graphene oxide, 3
      ml/h of feed speed, electrostatic field parameters was 9 kV and 20 cm, uniformly
      sized carboxymethyl chitosan-graphene oxide particles in the diameter range of
      250-300 MUm was successfully prepared. In NaCl saline, these particles could
      maintain stable for at least a week, while pristine carboxymethyl chitosan
      particles quickly collapsed within an hour. The results of loading experiments
      showed that carboxymethyl chitosan-graphene oxide particles could effectively
      adsorb gatifloxacin, ofloxacin, bovine serum albumin, lysozyme, doxorubicin
      hydrochloride. And gatifloxacin was chosen as a model drug to study the exact
      effect of graphene oxide content on the loading and release properties. In 40:2
      group, the highest loading capacity of 0.45 +/- 0.19 mg/mg was achieved, and also
      a good sustained release was available. Above all, we believed that carboxymethyl
      chitosan-graphene oxide particles as a versatile carrier, has great potential in
      Medicine and Pharmacy.

PMID- 27709460
TI  - A Prospective, Randomized, Open-Label Study to Evaluate Two Management Strategies
      for Gastrointestinal Symptoms in Patients Newly on Treatment with Dabigatran.
AB  - INTRODUCTION: In the pivotal RE-LY trial, dabigatran etexilate (DE) at the dose
      of 150-mg twice daily (BID), significantly reduced total stroke and ischemic
      stroke compared with warfarin in patients with non-valvular atrial fibrillation
      (NVAF), while the 110-mg BID dose had efficacy equivalent to warfarin, and major
      bleeds were significantly reduced. Both DE regimens were generally well
      tolerated; however, approximately 4% of the patients discontinued treatment with
      DE due to gastrointestinal (GI) discomfort. METHODS: Clinical trial NCT01493557
      was a multicenter, randomized, active control, open-label study to assess the
      efficacy of two simple GI symptom (GIS) management strategies in DE-treated
      patients who developed GIS: (1) concurrent treatment with the proton pump
      inhibitor pantoprazole (DE-P), or (2) ingestion of DE after a meal (DE-M).
      Patients were initially randomized to either GIS management strategy. If the
      first did not resolve their GIS, patients had the option to "add on" the
      alternative strategy. RESULTS: A total of 1067 patients with NVAF received DE
      therapy BID for 3 months (United States, 150-mg or 75-mg; Canada, 150-mg or 110
      mg). Of these, 117 (11%) patients reported GIS and were randomized to one of two
      GIS management strategies. At 4 weeks, a significantly higher rate of complete or
      partial effectiveness was observed in patients on DE-P than in those receiving DE
      M, [50/58 (86.2%) versus 40/59 (67.8%), respectively; p = 0.0273]. Patients with
      ongoing GIS were asked to "add on" the alternate strategy for an additional 4
      weeks. Overall, 92/117 (78.6%) of randomized patients experienced complete or
      partial effectiveness using either the initial strategy or a combination of the
      two strategies: DE-P, 47 (81.0%); and DE-M, 45 (76.3%, no significant difference)
      (by initial strategy). CONCLUSION: The majority of patients enrolled either did
      not experience GIS at all, or their GIS resolved using either one individually,
      or a combination of the two strategies described. TRIAL REGISTRATION:
      http://www.ClinicalTrials.gov identifier: NCT01493557.

PMID- 27709457
TI  - Defining Trends in Global Gene Expression in Arabian Horses with Cerebellar
      Abiotrophy.
AB  - Equine cerebellar abiotrophy (CA) is a hereditary neurodegenerative disease that
      affects the Purkinje neurons of the cerebellum and causes ataxia in Arabian
      foals. Signs of CA are typically first recognized either at birth to any time up
      to 6 months of age. CA is inherited as an autosomal recessive trait and is
      associated with a single nucleotide polymorphism (SNP) on equine chromosome 2
      (13074277G>A), located in the fourth exon of TOE1 and in proximity to MUTYH on
      the antisense strand. We hypothesize that unraveling the functional consequences
      of the CA SNP using RNA-seq will elucidate the molecular pathways underlying the
      CA phenotype. RNA-seq (100 bp PE strand-specific) was performed in cerebellar
      tissue from four CA-affected and five age-matched unaffected horses. Three
      pipelines for differential gene expression (DE) analysis were used
      (Tophat2/Cuffdiff2, Kallisto/EdgeR, and Kallisto/Sleuth) with 151 significant DE
      genes identified by all three pipelines in CA-affected horses. TOE1
      (Log2(foldchange) = 0.92, p = 0.66) and MUTYH (Log2(foldchange) = 1.13, p = 0.66)
      were not differentially expressed. Among the major pathways that were
      differentially expressed, genes associated with calcium homeostasis and
      specifically expressed in Purkinje neurons, CALB1 (Log2(foldchange) = -1.7, p <
      0.01) and CA8 (Log2(foldchange) = -0.97, p < 0.01), were significantly down
      regulated, confirming loss of Purkinje neurons. There was also a significant up
      regulation of markers for microglial phagocytosis, TYROBP (Log2(foldchange) =
      1.99, p < 0.01) and TREM2 (Log2(foldchange) = 2.02, p < 0.01). These findings
      reaffirm a loss of Purkinje neurons in CA-affected horses along with a potential
      secondary loss of granular neurons and activation of microglial cells.

PMID- 27709461
TI  - Quantification of Vibrio species in oysters from the Gulf of Mexico with two
      procedures based on MPN and PCR.
AB  - Oysters can accumulate potentially pathogenic water bacteria. The objective of
      this study was to compare two procedures to quantify Vibrio species present in
      oysters to determine the most sensitive method. We analyzed oyster samples from
      the Gulf of Mexico, commercialized in Mexico City. The samples were inoculated in
      tubes with alkaline peptone water (APW), based on three tubes and four dilutions
      (10-1 to 10-4). From these tubes, the first quantification of Vibrio species was
      performed (most probable number (MPN) from tubes) and bacteria were inoculated by
      streaking on thiosulfate-citrate-bile salts-sucrose (TCBS) petri dishes. Colonies
      were isolated for a second quantification (MPN from dishes). Polymerase chain
      reaction (PCR) was used to determine species with specific primers: ompW for
      Vibrio cholerae, tlh for Vibrio parahaemolyticus, and VvhA for Vibrio vulnificus.
      Simultaneously, the sanitary quality of oysters was determined. The
      quantification of V. parahaemolyticus was significantly higher in APW tubes than
      in TCBS dishes. Regarding V. vulnificus counts, the differences among both
      approaches were not significant. In contrast, the MPNs of V. cholerae obtained
      from dishes were higher than from tubes. The quantification of MPNs through PCR
      of V. parahaemolyticus and V. vulnificus obtained from APW was sensitive and
      recommendable for the detection of both species. In contrast, to quantify V.
      cholerae, it was necessary to isolate colonies on TCBS prior PCR. Culturing in
      APW at 42  degrees C could be an alternative to avoid colony isolation. The MPNs
      of V. cholerae from dishes was associated with the bad sanitary quality of the
      samples.

PMID- 27709462
TI  - Heavy metals relationship with water and size-fractionated sediments in rivers
      using canonical correlation analysis (CCA) case study, rivers of south western
      Caspian Sea.
AB  - Some pollutants can qualitatively affect aquatic freshwater such as rivers, and
      heavy metals are one of the most important pollutants in aquatic fresh waters.
      Heavy metals can be found in the form of components dissolved in these waters or
      in compounds with suspended particles and surface sediments. It can be said that
      heavy metals are in equilibrium between water and sediment. In this study, the
      amount of heavy metals is determined in water and different sizes of sediment. To
      obtain the relationship between heavy metals in water and size-fractionated
      sediments, a canonical correlation analysis (CCA) was utilized in rivers of the
      southwestern Caspian Sea. In this research, a case study was carried out on 18
      sampling stations in nine rivers. In the first step, the concentrations of heavy
      metals (Cu, Zn, Cr, Fe, Mn, Pb, Ni, and Cd) were determined in water and size
      fractionated sediment samples. Water sampling sites were classified by
      hierarchical cluster analysis (HCA) utilizing squared Euclidean distance with
      Ward's method. In addition, for interpreting the obtained results and the
      relationships between the concentration of heavy metals in the tested river water
      and sample sediments, canonical correlation analysis (CCA) was utilized. The
      rivers were grouped into two classes (those having no pollution and those having
      low pollution) based on the HCA results obtained for river water samples. CCA
      results found numerous relationships between rivers in Iran's Guilan province and
      their size-fractionated sediments samples. The heavy metals of sediments with
      0.038 to 0.125 mm size in diameter are slightly correlated with those of water
      samples.

PMID- 27709463
TI  - Multilocation field trials for risk assessment of a combination fungicide
      Fluopicolide + Propamocarb in tomato.
AB  - Dissipation kinetics of two systemic fungicides, namely fluopicolide and
      propamocarb used as a combination formulation (Infinito 68.75 SC), were studied
      on tomato at four different locations by the All India Network Project on
      Pesticide Residues to recommend their pre-harvest interval (PHI) and to propose
      the maximum residue limits (MRL) for the two fungicides based on chronic hazard
      exposure assessment. The combination fungicide was sprayed thrice at the
      recommended dosage of 93.75 g a.i./ha fluopicolide and 937.50 g a.i./ha
      propamocarb as well as at double the recommended dosage of 187.50 g a.i./ha
      fluopicolide and 1875.0 g a.i./ha propamocarb on tomato crops and the residues
      were monitored periodically by GC-MS. The fungicides dissipated to below the
      limit of quantification (LOQ) within 10 to 15 days, with a half-life of 2-4 days
      for fluopicolide and 1-2 days for propamocarb. Taking into consideration the MRLs
      of codex and calculations made using the method of MRL fixation of the Food
      Safety and Standard Authority of India (FSSAI) as well as the Organization for
      Economic Co-operation and Development (OECD) calculator, MRL of 5 mg/kg is
      proposed for fluopicolide and 15 mg/kg for propamocarb, following critical
      exposure of the commodity considering PHI of 1 day.

PMID- 27709464
TI  - Heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) in soils of
      different land uses in Erbil metropolis, Kurdistan Region, Iraq.
AB  - Urban soil contamination is a growing concern for the potential health impact on
      the increasing number of people living in these areas. In this study, the
      concentration, the distribution, the contamination levels, and the role of land
      use were investigated in Erbil metropolis, the capital of Iraqi Kurdistan. A
      total of 74 soil samples were collected, treated, and analyzed for their
      physicochemical properties, and for 7 heavy metals (As, Cd, Cr, Cu, Fe, Pb, and
      Zn) and 16 PAH contents. High concentrations, especially of Cd, Cu Pb, and Zn,
      were found. The Geoaccumulation index (Igeo), along with correlation coefficients
      and principal component analysis (PCA) showed that Cd, Cu, Pb, and Zn have
      similar behaviors and spatial distribution patterns. Heavy traffic density mainly
      contributed to the high concentrations of these metals. The total concentration
      of ?PAHs ranged from 24.26 to 6129.14 ng/g with a mean of 2296.1 ng/g. The PAH
      pattern was dominated by 4- and 5-ring PAHs, while diagnostic ratios and PCA
      indicated that the main sources of PAHs were pyrogenic. The toxic equivalent
      (TEQ) values ranged from 3.26 to 362.84 ng/g, with higher values in central parts
      of the city. A statistically significant difference in As, Cd, Cu, Pb, Zn, and
      ?PAH concentrations between different land uses was observed. The highest As
      concentrations were found in agricultural areas while roadside, commercial, and
      industrial areas had the highest Cd, Cu, Pb, Zn, and ?PAH contents.

PMID- 27709465
TI  - Leukotriene Receptor Antagonists for the Treatment of Asthma in Elderly Patients.
AB  - Elderly asthma (EA) is regarded as a distinct phenotype of asthma and is
      associated with age-related changes in airway structure and alterations in lung
      function and immune responses. EA is difficult to diagnose because of aging and
      co-morbidities, and overlaps with fixed airway obstructive disease. Novel
      modalities to differentiate between EA and chronic obstructive pulmonary disease
      (COPD) are necessary. A multifaceted approach, including clinical history,
      smoking habits, atopy, and measurement of lung function, is mandatory to
      differentiate asthma from COPD. There are a variety of co-morbidities with EA, of
      which COPD, upper airway diseases, depression, obesity, and hypertension are the
      most common, and these co-morbidities can affect the control status of EA.
      However, leukotriene receptor antagonists (LTRAs) can facilitate the management
      of EA, and thus addition of an LTRA to inhaled corticosteroid (ICS) monotherapy
      or ICS plus long-acting beta2-agonist therapy improves symptoms in EA patients.
      LTRA treatment is safe and beneficial in patients who are unable to use
      inhalation devices properly or who have co-morbid diseases. Therefore, clinical
      studies targeting a specific population of EA patients are warranted to help
      achieve a better therapeutic strategy in EA patients.

PMID- 27709468
TI  - Erratum to: Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic
      syndrome: insights on insulin resistance, inflammation, and atherogenic
      dyslipidemia.

PMID- 27709467
TI  - Biological Relevance of Free Radicals and Nitroxides.
AB  - Nitroxides are stable, kinetically-persistent free radicals which have been
      successfully used in the study and intervention of oxidative stress, a critical
      issue pertaining to cellular health which results from an imbalance in the levels
      of damaging free radicals and redox-active species in the cellular environment.
      This review gives an overview of some of the biological processes that produce
      radicals and other reactive oxygen species with relevance to oxidative stress,
      and then discusses interactions of nitroxides with these species in terms of the
      use of nitroxides as redox-sensitive probes and redox-active therapeutic agents.

PMID- 27709469
TI  - External ear invasion from an anaplastic thyroid cancer.

PMID- 27709466
TI  - Evaluating the Role of Hormone Therapy in Postmenopausal Women with Alzheimer's
      Disease.
AB  - Hormone therapy (HT) is prescribed during or after menopausal transition to
      replace the decline in estrogen and progesterone levels. While some studies
      indicate that estrogen and progesterone depletion in postmenopausal women might
      carry a significant risk for developing sporadic Alzheimer's disease (sAD), which
      may be reduced by HT, recent clinical trials oppose this beneficial effect. This
      review points to possible reasons for these mixed data by considering the issues
      of both preclinical and clinical trials, in particular, the representativeness of
      animal models, timing of HT initiation, type of HT (different types of estrogen
      compounds, estrogen monotherapy vs. estrogen-progesterone combined therapy), mode
      of drug delivery (subcutaneous, transdermal, oral, or intramuscular), and hormone
      dosage used, as well as the heterogeneity of the postmenopausal population in
      clinical trials (particularly considering their sAD stage, anti-AD therapy, and
      hysterectomy status). Careful planning of future preclinical and clinical HT
      interventional studies might help to elucidate the effect of HT on cognitive
      status in postmenopausal women with sAD, which will eventually contribute to more
      effective sAD prevention and treatment.

PMID- 27709470
TI  - Prospective, long-term study of the effect of cabergoline on valvular status in
      patients with prolactinoma and idiopathic hyperprolactinemia.
AB  - Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as
      it permits rapid and effective hormonal and tumor control in most cases. Evidence
      of cardiac valvulopathy was demonstrated in Parkinson's disease patients treated
      with dopamine agonists. Retrospective studies in prolactinoma patients treated
      with cabergoline at lower doses did not show such an effect. However, few
      prospective data with long-term follow-up are available. The aim of this study
      was to assess the safety of cabergoline regarding cardiac valvular status during
      prospective follow-up in patients treated for prolactinoma or idiopathic
      hyperprolactinemia. We report here a series of 100 patients (71F; median age at
      diagnosis: 41.5 years) treated with cabergoline for endocrine diseases
      (prolactinoma n = 89, idiopathic hyperprolactinemia n = 11). All patients
      underwent complete transthoracic echocardiographic studies at baseline and during
      long-term prospective surveillance using the same equipment and performed by the
      same technicians. The median interval between baseline and last follow-up
      echocardiographic studies while on cabergoline was 62.5 months (interquartile
      range: 34.75-77.0). The median total duration of cabergoline treatment was 124.5
      months (interquartile range: 80.75-188.75) and the median cumulative total dose
      of cabergoline was 277.8 mg (interquartile range : 121.4-437.8 mg) at last follow
      up. We found no clinically relevant alterations in cardiac valve function or
      valvular calcifications with cabergoline treatment. Our data suggest that
      findings from retrospective analyses are correct and that cabergoline is a safe
      chronic treatment at the doses used typically in endocrinology.

PMID- 27709471
TI  - Natural history of graves' orbitopathy after treatment.
AB  - Intravenous glucocorticoids are used for Graves' orbitopathy, alone or associated
      with/followed by additional treatments (orbital radiotherapy, orbital
      decompression, palpebral or eye surgery). However, the relation between
      associated/additional treatments and other variables with Graves' orbitopathy
      outcome following intravenous glucocorticoids is not clear. Thus, the present
      study was conducted to investigate retrospectively the impact of
      associated/additional treatments and other variables on Graves' orbitopathy
      outcome after intravenous glucocorticoids. We evaluated 226 untreated Graves'
      orbitopathy patients. Following first observation, patients were given
      intravenous glucocorticoids and re-examined after a median of 46.5 months. The
      end-points were the relation between Graves' orbitopathy outcome, outcome of
      NOSPECS score and of the single Graves' orbitopathy features with several
      variables, including associated/additional treatments. All Graves' orbitopathy
      features improved significantly after treatment. Overall, Graves' orbitopathy
      improved in ~60 % of patients (responders), whereas it was stable or worsened in
      ~40 % of patients (non-responders). Time between first and last observation and
      clinical activity score at first observation correlated significantly with
      Graves' orbitopathy outcome. The outcomes of NOSPECS, eyelid aperture, clinical
      activity score and diplopia correlated with time between the first and last
      observation. The NOSPECS outcome correlated with gender. The outcomes of
      proptosis, eyelid aperture and visual acuity correlated with orbital
      decompression. The outcome of diplopia correlated with orbital radiotherapy.
      Taking into account the limitations of retrospective investigations, our findings
      confirm that time (i.e. the natural history of Graves' orbitopathy) is a key
      factor in determining the long-term outcome of Graves' orbitopathy, radiotherapy
      is effective for diplopia, and orbital decompression is followed by an
      amelioration of several Graves' orbitopathy features.

PMID- 27709472
TI  - The effect of TSH change per year on the risk of incident chronic kidney disease
      in euthyroid subjects.
AB  - The objective of this study is to evaluate the predictive values of baseline
      thyroid-stimulating hormone and the rate of thyroid-stimulating hormone change
      within the euthyroid state on the development of chronic kidney disease. We
      conducted a longitudinal study in 17,067 Korean adults with normal thyroid
      function and no history of thyroid disease. Incident chronic kidney disease was
      defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2. The rate
      of thyroid-stimulating hormone change was determined by subtracting the baseline
      thyroid-stimulating hormone level from the thyroid-stimulating hormone level
      measured at the last visit prior to the diagnosis of chronic kidney disease or at
      the final visit in subjects without chronic kidney disease, divided by the
      observation period (years). Subjects were stratified into quintiles according to
      rates of thyroid-stimulating hormone change. During 86,583 person-years of follow
      up (median follow-up 5.2 years), there were 561 incident cases of chronic kidney
      disease. The risk of incident chronic kidney disease was significantly higher in
      subjects with rapid increases (quintile 5) or decreases (quintile 1) in thyroid
      stimulating hormone levels compared to the reference group (quintile 3). In fully
      adjusted models, the hazard ratios of quintiles 1 and 5 were 3.15 (95 %
      confidence interval 2.34 to 4.24; p < 0.001) and 3.37 (95 % confidence interval
      2.52 to 4.51; p < 0.001), respectively. However, there was no significant
      association between baseline thyroid-stimulating hormone and risk of incident
      chronic kidney disease. The development of chronic kidney disease is associated
      with the rate of changes in thyroid-stimulating hormone level rather than with
      baseline thyroid-stimulating hormone levels.

PMID- 27709473
TI  - Multiparametric ultrasonography and ultrasound elastography in the
      differentiation of parathyroid lesions from ectopic thyroid lesions or
      lymphadenopathies.
AB  - To evaluate the accuracy of ultrasound elastography with ElastoscanTM Core Index
      in the differential diagnosis of parathyroid lesions from ectopic thyroid nodules
      and lymph nodes. Seventy nine patients with repeatedly high levels of circulating
      intact parathyroid hormone, normal vitamin D and renal function tests, with an
      ultrasound scan showing a neck lesion, sharply demarcated from the thyroid
      lobules, were consecutively enrolled. Ultrasound with and without Color Doppler
      and ultrasound elastography were performed before histological examination. All
      ultrasound features, vascularization and ultrasound elastography diagnostic
      performance were assessed using ROC curves. Histological examination confirmed 47
      parathyroid lesions, 18 thyroid ectopic nodules and 14 reactive lymph nodes. In
      distinguishing parathyroid from thyroid nodules, shape had a 100 % sensitivity
      (95 % CI 92.4-100) and 50 % specificity (95 % CI 37.2-64.7), cleavage had a 85.1
      % sensitivity (95 % CI 72.3-92.6) and 77.8 % specificity (95 % CI 65.1-88) while
      peripheral vascularization had a sensitivity of 91.5 (95 % CI 79.6-97.6) and
      specificity of 72.2 (95 % CI 46.5-90.3). An ElastoscanTM Core Indexof 1.28 was 46
      % sensitive (95 % CI 33.4-58.7) and 77 % specific (95 % CI 66.2-89.1) in
      discriminating parathyroid lesions from thyroid nodules. An ElastoscanTM Core
      Index of 1.0 was 78 % sensitive (95 % CI 65.1-88) and 71 % specific (95 % CI 56
      81.3) in discriminating parathyroid lesions from lymph nodes (p = 0.045). An
      ElastoscanTM Core Index greater than 2.58 had a 100 % sensitivity (95 % CI 43.8
      100) and 95.4 % specificity (95 % CI 38.3-99.7) in discriminating malignant from
      benign parathyroid nodules. ElastoscanTM Core Index was significantly higher in
      thyroid nodules than in reactive lymph nodes (1.18 +/- 0.62, p = 0.008). The
      ultrasound features of cleavage and peripheral vascularization help to
      differentiate parathyroid from thyroid nodules. ElastoscanTM Core Index can
      improve ultrasound discrimination of parathyroid lesions from lymph nodes. The
      ElastoscanTM Core Index is significantly higher in malignant than in benign
      parathyroid lesions.

PMID- 27709474
TI  - Identifying the culprit lesion in tumor induced hypophosphatemia, the solution of
      a clinical enigma.
AB  - Tumor-induced osteomalacia is a rare acquired metabolic bone disorder
      characterized by isolated renal phosphate wasting due to abnormal tumor
      production of fibroblast growth factor 23. We report the case of a 59 year old
      woman referred to our department with a long history of progressive diffuse
      muscle weakness and pain, generalized bone pains and multiple insufficiency
      fractures of heels, ankles and hips due to a hypophosphatemic osteomalacia. A
      fibroblast growth factor 23-producing phosphaturic mesenchymal tumor localized in
      the left quadriceps femoris muscle was identified 7 years after onset of
      symptoms. Excision of the tumor resulted in normalization of serum phosphate and
      fibroblast growth factor 23 levels and in complete resolution of the clinical
      picture with disappearance of all musculoskeletal symptoms. This case illustrates
      the diagnostic difficulties in establishing a diagnosis tumor-induced
      osteomalacia and in identifying the responsible tumor. Our case underscores the
      clinical need to investigate all patients with persistent musculoskeletal
      symptoms for hypophosphatemia. A systematic approach is of pivotal importance
      because early recognition and treatment of the metabolic abnormality can prevent
      deleterious effects of osteomalacia on the skeleton.

PMID- 27709475
TI  - Differentiated thyroid carcinoma: Incremental diagnostic value of 131I SPECT/CT
      over planar whole body scan after radioiodine therapy.
AB  - The purpose of this prospective study was to determine the incremental diagnostic
      value of single photon emission computed tomography/computed tomography with
      iodine-131 over planar whole body scan in the staging of patients with
      differentiated thyroid carcinoma. A total of 365 patients (270 female, 95 male)
      with differentiated thyroid carcinoma were treated with radioiodine therapy for
      thyroid remnant ablation with radical intent after thyroidectomy between January
      2013 and November 2014. In addition to planar whole body scan, single photon
      emission computed tomography/computed tomography of neck and chest were
      performed. Each radioactive focus at whole body scan was classified as positive
      or equivocal with respect of specific territories: thyroid bed, cervical lymph
      nodes and distant metastases.Whole-body scan detected focal uptake in 353
      patients and no uptake in 12. The location was considered equivocal in 100.
      Single photon emission computed tomography/computed tomography detected focal
      uptake in 356 patients and no uptake in nine. In three patients with negative
      wholebody scan, single photon emission computed tomography/computed tomography
      provided information about residual activity in the thyroid bed. By single photon
      emission computed tomography/computed tomography the location was equivocal in 18
      patients only. Single photon emission computed tomography/computed tomography was
      helpful in 82 out of 100 patients with equivocal findings by whole body scan
      allowing a correct identification of the uptake sites. In a great number of
      equivocal whole body scan, due to high remnant activity, single photon emission
      computed tomography/computed tomography was able to differentiate between thyroid
      remnant and lymph nodes uptake. In 22 out of 100 patients with doubtful whole
      body scan, single photon emission computed tomography/computed tomography
      correctly identified nodal or distant metastases, and in 2/100 patients, focal
      uptake classified as metastatic by whole body scan was reclassified as para
      physiological by single photon emission computed tomography/computed tomography.
      The TNM classification changed in 13 out of 22 patients. Single photon emission
      computed tomography/computed tomography improves detection and localization of
      the iodine-131 uptake after thyroidectomy in patients with differentiated thyroid
      carcinoma and it is more accurate than whole body scan to evaluate lymph nodes
      and to identify and characterize distant metastases. Single photon emission
      computed tomography/computed tomography aids assessment of lower/upper stage in a
      significant number of patients with differentiated thyroid carcinoma and it can
      affect therapy decision-making and patient management.

PMID- 27709485
TI  - Pediatric anterior cruciate ligament reconstruction outcomes.
AB  - Treatment of pediatric anterior cruciate injuries have become an area of
      controversy sparking much debate about best management strategies. Delaying
      surgery until skeletal maturity has often been shown to result in unfavorable
      outcomes due to concomitant meniscal and chondral injuries in this population.
      There have been numerous techniques used to reconstruct the ACL in the skeletally
      immature patient; however, most studies are limited by small patient numbers and
      other methodological concerns. With recent publications reporting failure rates
      as high as 15-25 % and growth disturbances being uncommon but now reported within
      almost every technical category, patient and caregiver education become of
      paramount importance. Key principles will be outlined that may help to avoid some
      of the pitfalls that occur when dealing with this unique population.

PMID- 27709476
TI  - Parenchyma-sparing surgery for pancreatic endocrine tumors.
AB  - Enucleation (EN) and middle pancreatectomy (MP) have been proposed as a treatment
      for G1 and G2 pancreatic neuroendocrine tumors (PNET). The aim of this study is
      to analyze the outcomes of parenchyma-sparing surgery (PSS) for PNET in an
      Italian high-volume center. All patients with a histological diagnosis of PNET
      who underwent surgical resection in our center between January 2010 and January
      2016 were included in the study. Demographic, perioperative, and discharge data
      were collected in a prospective database. Follow-up was considered until March
      31, 2016. 99 patients were included. PSS was performed in 22 cases (22.2 %), 18
      EN (82 %), and 4 MP (18 %). 89.8 % patients were staged with CT scan, 69.6 % with
      endoscopic ultrasonography, 48.4 % with MRI, and 47.4 % with 68Ga-PET. Pre
      operative histological diagnosis was obtained in 68.6 %. Most of PSS tumors were
      G1 (n = 15; 68 %) and there were no G3. Nodal sampling was performed in every
      PSS. Only two patients showed nodal metastatic disease. The median post-operative
      length of stay was 7 days after PSS. Eleven (50 %) of these patients developed a
      complication; two (18.2 %) were major complications. Pancreatic fistula developed
      in ten patients (45.5 %); two (20 %) were type B. There were no type C fistula
      and no re-operations after PSS. Readmission rate was 9 %. All patients submitted
      to PSS are alive and free of recurrence. PSS is a safe technique for G1 and G2
      PNETs, but it has to be conducted in experienced centers and an extensive nodal
      sampling and a long follow-up are required for the best oncologic outcome.

PMID- 27709486
TI  - Lower extremity growth and deformity.
AB  - The pediatric lower extremity has well known growth patterns. When deformities or
      growth disturbances occur, there are several methods to measure and predict the
      resulting discrepancy, including the Green-Anderson, Moseley, and Multiplier
      methods. Many techniques exist to correct leg length discrepancy and deformity
      such and temporary epiphysiodesis, permanent epiphysiodesis, external fixators,
      and internal lengthening devices. All of these methods have numerous
      complications and limitations; however, with careful planning and patient
      selection, length and alignment can be improved with high patient satisfaction.

PMID- 27709488
TI  - Criteria for Inclusion of Newer Bariatric and Metabolic Procedures into the
      Mainstream: a Survey of 396 Bariatric Surgeons.
AB  - BACKGROUND: There is currently no consensus on the criteria for inclusion of new
      bariatric procedures into routine clinical practice. This study canvasses
      bariatric surgeons in an attempt to define these criteria. METHODS: Bariatric
      Surgeons from around the world were invited to participate in a questionnaire
      based survey on SurveyMonkey (r). RESULTS: 396 bariatric surgeons, 337
      International Federation for the Surgery of Obesity and Metabolic Disorders
      (IFSO) members, took the survey. Five clinical studies conducted under the strict
      monitoring of an Institutional Review Board would satisfy most surgeons (67.7 %,
      n = 266). When asked regarding the number of patients in these studies, a
      cumulative number of 500 patients would satisfy 64.5 % (n = 255) of the surgeons.
      Most respondents regarded endorsement by their national society and IFSO as 'very
      important' or 'extremely important'. An overwhelming 74.4 % (n = 294) felt that
      every new procedure should undergo a randomized comparison against one of the
      established alternatives like Roux-en-Y Gastric Bypass or Sleeve Gastrectomy.
      CONCLUSION: Evaluation of a new bariatric procedure in at least 5 adequately
      supervised clinical studies (four of which must be randomized comparisons with
      one of the existing alternatives) reporting at least 5 years results on a minimum
      of 500 patients would satisfy majority of bariatric surgeons for the inclusion of
      a new bariatric procedure into clinical practice. The findings of this survey are
      simply aimed at starting a discussion on this topic and cannot be used to
      influence the ground reality until an international consensus can be reached
      amongst experts.

PMID- 27709487
TI  - Long-Term Outcomes in Patients with Morbid Obesity and Type 1 Diabetes Undergoing
      Bariatric Surgery.
AB  - BACKGROUND: This study aims to describe the long-term outcomes of bariatric
      surgery in a cohort of patients with type 1 diabetes (T1DM). METHODS: Thirty-two
      patients with T1DM and initial BMI of 41.3 +/- 4.8 kg/m2 were studied, 18.7 %
      undergoing duodenal switch (DS), 34.4 % gastric bypass, and 46.9 % sleeve
      gastrectomy and followed-up after surgery for 4.6 +/- 2.6 years. Changes in BMI,
      HbA1c, insulin requirements, evolution of comorbidities, and microvascular
      complications were registered annually after surgery. RESULTS: Percentage of
      total weight loss (%TWL) 12 months after surgery was 30.4 +/- 9.2 % and at 5
      years, it decreased to 28.1 +/- 11.5 % (p = 0.02). HbA1c was reduced during the
      first year from 8.5 +/- 1.3 to 7.9 +/- 1.4 %, p = 0.016. In the long-term, HbA1c
      returned to baseline values. There was a sustained reduction of 51 % in total
      daily insulin dose, and the decrease in the number of patients with hypertension,
      dyslipidemia, and obstructive sleep apnea was 42.8, 25, and 66 %, respectively.
      Retinopathy remained mainly unaffected, and 25 % of patients with
      microalbuminuria regressed to normoalbuminuria. CONCLUSIONS: Bariatric surgery in
      patients with T1DM mainly provides benefits of weight reduction, on insulin
      requirements, obesity comorbidities, and some benefits in diabetes complications,
      but might have only minimal effect on the glycemic control in the long term. This
      trial was registered at www.controlledtrials.com as ISRCTN49980913.

PMID- 27709489
TI  - The role of FDG-PET/CT in preoperative staging of sentinel lymph node biopsy
      positive melanoma patients.
AB  - BACKGROUND: On April 1, 2015, Odense University Hospital (OUH) began a new
      diagnostic strategy, wherein all malignant melanoma (MM) patients in the Region
      of Southern Denmark with a positive sentinel lymph node biopsy (SLNB) underwent
      FDG-PET/CT preoperatively prior to lymph node dissection (LND). The purpose of
      this study is to determine FDG-PET/CT's efficacy in finding distant metastasis in
      the first year after the implementation of this new strategy, and to what extent
      these findings influence subsequent diagnostic testing and treatment in this
      patient group. We conducted a retrospective multicenter cohort study which
      included all patients with MM from all hospitals in the Region of Southern
      Denmark from April 1, 2015 to April 1, 2016 found to be SLNB-positive who
      subsequently underwent FDG-PET/CT. Patient information was acquired from the
      Danish Melanoma Database and was cross-referenced with OUH's patient records. The
      data was analyzed for a number of parameters including FDG-PET/CT findings and
      treatment strategy. Median follow-up time was 7 months. RESULTS: A total of 47
      patients were eligible from the first year of this new diagnostic strategy. One
      patient was excluded due to undergoing LND prior to FDG-PET/CT. Thus, 46 patients
      were included in this study. Ultimately, preoperative FDG-PET/CT neither
      uncovered any distant metastases nor led to any alterations in treatment strategy
      in this patient group. CONCLUSIONS: Surprisingly, this new diagnostic strategy
      did not find any MM metastases or uncover anything else of relevance. FDG-PET/CT
      did, however, provide false positive findings in 13 % (6/46) of these patients.
      These scans triggered additional, predominantly invasive, procedures, which did
      not ultimately have an impact on the therapeutic strategy. Thus, these findings
      indicate a need for re-evaluation of this new diagnostic strategy as well as the
      necessity for further clinical trials evaluating FDG-PET/CT's utility in this
      clinical setting.

PMID- 27709490
TI  - Atorvastatin Protects from Abeta1-40-Induced Cell Damage and Depressive-Like
      Behavior via ProBDNF Cleavage.
AB  - Intracerebroventricular (icv) amyloid-beta (Abeta)1-40 infusion to mice has been
      demonstrated to cause neurotoxicty and depressive-like behavior and it can be
      used to evaluate antidepressant and neuroprotective effect of drugs. Atorvastatin
      is a widely used statin that has demonstrated antidepressant-like effect in
      predictable animal behavioral models and neuroprotective effect against Abeta1-40
      infusion. The purpose of this study was to determine the effect of in vivo
      atorvastatin treatment against Abeta1-40-induced changes in mood-related
      behaviors and biochemical parameters in ex vivo hippocampal slices from mice.
      Atorvastatin treatment (10 mg/kg, p.o., once a day for seven consecutive days)
      abolished depressive-like and anhedonic-like behaviors induced by Abeta1-40 (400
      pmol/site, icv) infusion. Abeta1-40-induced hippocampal cell damage was reversed
      by atorvastatin treatment. Abeta1-40 infusion decreased glutamate uptake in
      hippocampal slices, and atorvastatin did not altered it. Glutamine synthetase
      activity was not altered by any treatment. Atorvastatin also increased
      hippocampal mature brain-derived neurotrophic factor (mBDNF)/precursor BDNF
      (proBDNF) ratio, suggesting an increase of proBDNF to mBDNF cleavage.
      Accordingly, increased tissue-type plasminogen activator (tPA) and p11 genic
      expression were observed in hippocampus of atorvastatin-treated mice.
      Atorvastatin displays antidepressant-like and neuroprotective effects against
      Abeta1-40-induced toxicity, and these effects may involve tPA- and p11-mediated
      cleavage of proBDNF to mBDNF.

PMID- 27709492
TI  - C5a/C5aR Pathway Plays a Vital Role in Brain Inflammatory Injury via Initiating
      Fgl-2 in Intracerebral Hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a serious emergency with high mortality and
      morbidity. Up to date, a limited understanding of ICH pathogenesis is difficult
      to implement effective therapeutic strategy. Much evidence demonstrates that the
      complement cascade is activated after experimental ICH. However, the exact
      mechanism has not been well studied in ICH. In the current study, C57BL/6J mice
      were injected with autologous whole blood. C5a/C5aR levels, microglia
      infiltration, inflammatory cytokine, and fibrinogen-like protein 2 (Fgl-2)
      expression in the perihematomal region were analyzed following ICH. In addition,
      brain water content and neurological dysfunction were detected following ICH. Our
      data demonstrated that ICH induced complement activation, along with an increase
      of C5a/C5aR levels, microglia infiltration, and inflammatory cytokine levels.
      However, C5aR-/- mice exhibited significant attenuation of inflammatory reaction,
      accompanied by a remarkable reduction of Fgl-2, brain water content, and
      neurological dysfunction. Furthermore, inhibiting extracellular signal-regulated
      kinase 1/2 (ERK1/2) and p38 efficiently inhibited C5a-mediated Fgl-2 production
      following ICH. Taken together, these data suggest that C5a/C5aR plays a vital
      role in the ICH-induced inflammatory damage via Fgl-2, and ERK1/2 and p38
      pathways also are involved in the pathogenesis of ICH. Therefore, inhibition of
      C5a/C5aR activation might enlarge our insights in ICH therapy.

PMID- 27709491
TI  - P2X3 and P2X2/3 Receptors Play a Crucial Role in Articular Hyperalgesia
      Development Through Inflammatory Mechanisms in the Knee Joint Experimental
      Synovitis.
AB  - Osteoarthritis (OA) is a degenerative and progressive disease characterized by
      cartilage breakdown and by synovial membrane inflammation, which results in
      disability, joint swelling, and pain. The purinergic P2X3 and P2X2/3 receptors
      contribute to development of inflammatory hyperalgesia, participate in arthritis
      processes in the knee joint, and are expressed in chondrocytes and nociceptive
      afferent fibers innervating the knee joint. In this study, we hypothesized that
      P2X3 and P2X2/3 receptors activation by endogenous ATP (adenosine 5'
      triphosphate) induces articular hyperalgesia in the knee joint of male and female
      rats through an indirect sensitization of primary afferent nociceptors dependent
      on the previous release of pro-inflammatory cytokines and/or on neutrophil
      migration. We found that the blockade of articular P2X3 and P2X2/3 receptors
      significantly attenuated carrageenan-induced hyperalgesia in the knee joint of
      male and estrus female rats in a similar manner. The carrageenan-induced knee
      joint inflammation increased the expression of P2X3 receptors in chondrocytes of
      articular cartilage. Further, the blockade of articular P2X3 and P2X2/3 receptors
      significantly reduced the increased concentration of TNF-alpha, IL-6, and CINC-1
      and the neutrophil migration induced by carrageenan. These findings indicate that
      P2X3 and P2X2/3 receptors activation by endogenous ATP is essential to
      hyperalgesia development in the knee joint through an indirect sensitization of
      primary afferent nociceptors dependent on the previous release of pro
      inflammatory cytokines and/or on neutrophil migration.

PMID- 27709493
TI  - G-CSF-mobilized Bone Marrow Mesenchymal Stem Cells Replenish Neural Lineages in
      Alzheimer's Disease Mice via CXCR4/SDF-1 Chemotaxis.
AB  - Recent studies reported granulocyte colony-stimulating factor (G-CSF) treatment
      can improve the cognitive function of Alzheimer's disease (AD) mice, and the
      mobilized hematopoietic stem cells (HSCs) or bone marrow mesenchymal stem cells
      (BM-MSCs) are proposed to be involved in this recovery effect. However, the exact
      role of mobilized HSC/BM-MSC in G-CSF-based therapeutic effects is still unknown.
      Here, we report that C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived
      factor 1 (SDF-1) chemotaxis was a key mediator in G-CSF-based therapeutic
      effects, which was involved in the recruitment of repair-competent cells.
      Furthermore, we found both mobilized HSCs and BM-MSCs were able to infiltrate
      into the brain, but only BM-MSCs replenished the neural lineage cells and
      contributed to neurogenesis in the brains of AD mice. Together, our data show
      that mobilized BM-MSCs are involved in the replenishment of neural lineages
      following G-CSF treatment via CXCR4/SDF-1 chemotaxis and further support the
      potential use of BM-MSCs for further autogenically therapeutic applications.

PMID- 27709496
TI  - Dietary Supplementation of Magnesium Oxide (MgO) Nanoparticles for Better
      Survival and Growth of the Freshwater Prawn Macrobrachium rosenbergii Post
      larvae.
AB  - This study was performed to assess the growth-promoting potential of dietary
      magnesium oxide nanoparticles (MgO NPs) in Macrobrachium rosenbergii post-larvae
      (PL). MgO NPs were supplemented at 0, 100, 200, 300, 400 and 500 mg kg-1 with the
      basal diet (containing 0.95 g Mg kg-1); the concentrations of Mg in MgO NP
      supplemented diets were increased correspondingly (1.07, 1.15, 1.24, 1.37 and
      1.46 g Mg kg-1 respectively). MgO NP-supplemented diets were fed to M.
      rosenbergii PL (initial weight 0.11 +/- 0.04 g) for a period of 90 days. In the
      carcasses of experimental prawns, the content of Mg was found to be elevated
      significantly with respect to the individual diet (102.14, 183.29, 205.46,
      221.03, 237.10 and 254.36 MUg Mg g-1 respectively) when compared with that of the
      control. The contents of Cu, Zn, Fe, Ca, Na and K levels were also found to be
      elevated in the carcasses of experimental prawns. Significant (P < 0.05)
      improvements were observed in nutritional indices [survival rate (SR), weight
      gain (WG), specific growth rate (SGR), feed conversion ratio (FCR) and protein
      efficiency ratio (PER)], activities of digestive enzymes (protease, amylase and
      lipase), concentrations of basic biochemical constituents (total protein, amino
      acid, carbohydrate, lipid, profiles of amino acids and fatty acids) and
      population of haemocytes [total and differential (hyalinocytes, semigranulocytes
      and granulocytes)] in all the test PL. Maximum performance was recorded in 500 mg
      kg-1 MgO NP-supplemented-feed-fed PL. There were no significant elevations
      recorded in activities of antioxidant enzymes [superoxide dismutase (SOD) and
      catalase (CAT)], lipid peroxidation (LPO) and metabolic enzymes [glutamic
      oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)] recorded
      in any of the MgO NP-supplemented-feed-fed PL when compared with the control.
      Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed
      increases in the staining intensity of polypeptide bands resolved in 500 mg kg-1
      MgO NP-supplemented-feed-fed PL when compared with the control. Based on the
      gradual improvement in attaining survival, growth, FCR, biochemical constituents
      and haemocyte population, this study recommends MgO NP supplementation of 500 mg
      kg-1 for sustainable maintenance of M. rosenbergii PL. As the studied highest
      concentration of MgO NPs showed the best performance, it is necessary to study
      with beyond 500 mg kg-1 of MgO NPs to optimize the actual concentration.

PMID- 27709494
TI  - Identification of Noncanonical Wnt Receptors Required for Wnt-3a-Induced Early
      Differentiation of Human Neural Stem Cells.
AB  - Wnt proteins preferentially activate either beta-catenin-dependent or beta
      catenin-independent signals, but the activity of a particular Wnt also depends on
      cellular context and receptor availability. We previously reported that Wnt-3a
      induces neural differentiation of human embryonic stem cell-derived neural stem
      cells (NSCs) in a beta-catenin-independent manner by activating a signal
      involving JNK and the AP-1 family member ATF-2. Here, we report the results of a
      gene silencing approach to identify the Wnt receptors that mediate this response
      to Wnt-3a. Silencing of ROR2 increased neuronal differentiation, as measured by
      expression of the genes DCX, NEUROD1, and NGN1, suggesting ROR2 signals normally
      prevent differentiation. Silencing of the other Wnt receptors singly did not
      affect Wnt-3a-induced neuronal differentiation. However, pairwise silencing of
      ROR1 and FZD4 or FZD5 and of LRP6 and FZD4 or FZD5 inhibited neuronal
      differentiation, as detected by reductions in the expression of neuronal genes
      and immunocytochemical detection of DCX, NEUROD1 and DCX. Ectopic expression of
      these receptors in HEK 293 cells increased ATF2-dependent transcription. In
      addition, ROR1 coimmunoprecipitated with FZD4 and LRP6 in transfected HEK 293
      cells and colocalized with FZD4 and with LRP6 at the cell surface of transfected
      L cells. Wnt-3a did not appear to affect these interactions but did alter the
      interactions between LRP6 and FZD4/5. Together, these observations highlight
      roles for ROR1, LRP6, FZD4, and FZD5 in neural stem cell differentiation and
      provide support for a model in which dynamic interactions among these receptors
      mediate Wnt-3a activation of ATF2 signaling.

PMID- 27709497
TI  - Cardioprotective Effect of Selenium Against Cyclophosphamide-Induced
      Cardiotoxicity in Rats.
AB  - The objective of this study is to evaluate the possible protective effects of
      selenium (Se) against cyclophosphamide (CP)-induced acute cardiotoxicity in rats.
      A total of 42 male Spraque-Dawley rats were divided into six groups (n = 7). Rats
      in the first group were served as control. Rats in the second group received CP
      (150 mg/kg) at the sixth day of experiment. Animals in the third and fourth
      groups were treated with only 0.5 and 1 mg/kg Se respectively for six consecutive
      days. Rats in the fifth and sixth groups received respective Se doses (0.5 or 1
      mg/kg) for 6 days and then a single dose of CP administered on the sixth day. On
      day 7, the animals were sacrificed; blood samples were collected to measure
      malondialdehyde (MDA), glutathione (GSH), lactate dehydrogenase (LDH), creatine
      kinase-MB (CK-MB), and ischemia-modified albumin (IMA) levels. Heart tissues were
      processed routinely and tissue sections were stained with H + E for light
      microscopic examination. In the CP-treated rats MDA, LDH, CK-MB, and IMA serum
      levels increased, while GSH levels decreased. Microscopic evaluation showed that
      tissue damage was conspicuously lower in CP plus Se groups. Moreover, 1 mg/kg Se
      was more protective than 0.5 mg/kg Se as indicated by histopathological and
      biochemical values. In conclusion, Se is suggested to be a potential candidate to
      ameliorate CP-induced cardiotoxicity which may be related to its antioxidant
      activity.

PMID- 27709495
TI  - Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol
      Drinking in Young Adult Rats and Humans.
AB  - Alcohol misuse has been linked to dysregulation of stress, emotion, and reward
      brain circuitries. A candidate key mediator of this association is the FK506
      binding protein (FKBP5), a negative regulator of the glucocorticoid receptor. The
      aim of the present study was to further understand the Fkbp5/FKBP5-related
      genetic underpinnings underlying the relationship between early life social
      relations and alcohol drinking. The effect of maternal separation and voluntary
      alcohol drinking on Fkbp5 expression was investigated in the brain of young adult
      rats, whereas the interaction effect of the functional FKBP5 single nucleotide
      polymorphism rs1360780 genotype and parent-child relationship on problematic
      drinking was examined in young adult humans. In rats, Fkbp5 expression in the
      nucleus accumbens and ventral tegmental area, core regions of the reward system,
      was affected in a region-dependent manner and in opposite direction by maternal
      separation and alcohol drinking. Fkbp5 expression in the cingulate cortex was
      affected by the combined effect of maternal separation and alcohol drinking. In
      humans, the TT genotype, in the presence of a poor relationship between the child
      and parents, was associated with problematic drinking behavior. The present
      findings suggest that Fkbp5 expression in mesocorticolimbic dopaminergic regions
      associates with early life stress-mediated sensitivity to alcohol drinking and
      that FKBP5 genotype interacts with parent-child relationship to influence alcohol
      drinking. These findings are the first to point to a role of FKBP5 in propensity
      to alcohol misuse and call for studies of the underlying molecular mechanisms to
      identify potential drug targets.

PMID- 27709498
TI  - Aluminum-Induced Cholinergic Deficits in Different Brain Parts and Its
      Implications on Sociability and Cognitive Functions in Mouse.
AB  - Aluminum is associated with etiology of many neurodegenerative diseases specially
      Alzheimer's disease. Chronic exposure to aluminum via drinking water results in
      aluminum deposition in the brain that leads to cognitive deficits. The study
      aimed to determine the effects of aluminum on cholinergic biomarkers, i.e.,
      acetylcholine level, free choline level, and choline acetyltransferase gene
      expression, and how cholinergic deficit affects novel object recognition and
      sociability in mice. Mice were treated with AlCl3 (250 mg/kg). Acetylcholine
      level, free choline level, and choline acetyltransferase gene expression were
      determined in cortex, hippocampus, and amygdala. The mice were subjected to
      behavior tests (novel object recognition and social novelty preference) to assess
      memory deficits. The acetylcholine level in cortex and hippocampus was
      significantly reduced in aluminum-treated animals, as compared to cortex and
      hippocampus of control animals. Acetylcholine level in amygdala of aluminum
      treated animals remained unchanged. Free choline level in all the three brain
      parts was found unaltered in aluminum-treated mice. The novel object recognition
      memory was severely impaired in aluminum-treated mice, as compared to the control
      group. Similarly, animals treated with aluminum showed reduced sociability
      compared to the control mice group. Our study demonstrates that aluminum exposure
      via drinking water causes reduced acetylcholine synthesis in spite of normal free
      choline availability. This deficit is caused by reduced recycling of
      acetylcholine due to lower choline acetyltransferase level. This cholinergic
      hypofunction leads to cognitive and memory deficits. Moreover, hippocampus is the
      most affected brain part after aluminum intoxication.

PMID- 27709505
TI  - A novel thymidine phosphorylase mutation in a Chinese MNGIE patient.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal
      recessive disorder associated with mitochondrial alterations. MNGIE is
      characterized by severe gastrointestinal dysmotility, cachexia, ophthalmoplegia,
      ptosis, peripheral neuropathy, and leukoencephalopathy. The condition is caused
      by mutation of the TYMP gene. We studied the clinical and biochemical
      characteristics of a family with MNGIE. The proband was a 48-year-old male
      presenting with diarrhea and progressive weight loss. He also had ptosis and
      exhibited eyeball fixation. His blood and cerebrospinal fluid lactate levels were
      elevated. Magnetic resonance imaging of the brain revealed diffuse
      leukoencephalopathy. Ragged red fibers and cytochrome c oxidase-deficient fibers
      were apparent on muscle biopsy. His vision and ptosis deteriorated significantly
      during follow-up. Our clinical diagnosis of MNGIE was confirmed by TYMP gene
      analysis. We discovered a homozygous TYMP c.1193-1216 dup
      GGGCGCTGCCGCTGGCGCTGGTGC mutation (a duplication). Some of the family members
      were heterozygous for the mutation but had no clinical features. We predicted the
      function of this mutation using PredictProtein and found that the secondary
      structure had changed in the region of the helix and strand, the transmembrane
      region, and the protein-protein binding sites. The family described herein
      exhibited biochemically, genetically, and functionally confirmed MNGIE syndrome.

PMID- 27709504
TI  - Understanding Long-Term Outcomes Following Sepsis: Implications and Challenges.
AB  - Sepsis is life-threating organ dysfunction due to infection. Incidence of sepsis
      is increasing and the short-term mortality is improving, generating more sepsis
      survivors. These sepsis survivors suffer from additional morbidities such as
      higher risk of readmissions, cardiovascular disease, cognitive impairment and of
      death, for years following index sepsis episode. In the first year following
      index sepsis episode, approximately 60 % of sepsis survivors have at least one
      rehospitalisation episode, which is most often due to infection and one in six
      sepsis survivors die. Sepsis survivors also have a higher risk of cognitive
      impairment and cardiovascular disease contributing to the reduced life expectancy
      seen in this population, when assessed with life table comparisons. For optimal
      design of interventional trials to reduce these bad outcomes in sepsis survivors,
      in-depth understanding of major risk factors for these morbid events, their
      modifiability and a causal relationship to the pathobiology of sepsis is
      essential. This review highlights the recent advances, clinical and
      methodological challenges in our understanding of these morbid events in sepsis
      survivors.

PMID- 27709506
TI  - Asymmetric sensory nerve action potential amplitudes as an early hint for
      diagnosing Lewis-Sumner syndrome.

PMID- 27709508
TI  - Erratum to: Chloroplast-Based Expression of Recombinant Proteins by Gateway(r)
      Cloning Technology.

PMID- 27709507
TI  - Cerebral venous sinus thrombosis presenting as subarachnoid haemorrhage.

PMID- 27709509
TI  - Effects of Incretin-Based Therapies and SGLT2 Inhibitors on Skeletal Health.
AB  - Anti-diabetic drugs are widely used and are essential for adequate glycemic
      control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs
      include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors)
      and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known
      detrimental effects of thiazolidinediones on bone metabolism and fracture risk,
      clinical data on the safety of incretin-based therapies is limited. Based on meta
      analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor
      agonists and DPP4 inhibitors, it seems that incretin-based therapies are not
      associated with an increase in fracture risk. Sodium-glucose co-transporter 2
      inhibitors may alter calcium and phosphate homeostasis as a result of secondary
      hyperparathyroidism induced by increased phosphate reabsorption. Although these
      changes may suggest detrimental effects of SGLT-2 inhibitors on skeletal
      integrity, treatment-related direct effects on bone metabolism seem unlikely.
      Observed changes in BMD, however, seem to result from increased bone turnover in
      the early phase of drug-induced weight loss. Fracture risk, which is observed in
      older patients with impaired renal function and elevated cardiovascular disease
      risk treated with SGLT2 inhibitors, seems to be independent of direct effects on
      bone but more likely to be associated with falls and changes in hydration status
      secondary to osmotic diuresis.

PMID- 27709510
TI  - Where Does the Electron Go? Stable and Metastable Peptide Cation Radicals Formed
      by Electron Transfer.
AB  - Electron transfer to doubly and triply charged heptapeptide ions containing polar
      residues Arg, Lys, and Asp in combination with nonpolar Gly, Ala, and Pro or Leu
      generates stable and metastable charge-reduced ions, (M + 2H)+?, in addition to
      standard electron-transfer dissociation (ETD) fragment ions. The metastable (M +
      2H)+? ions spontaneously dissociate upon resonant ejection from the linear ion
      trap, giving irregularly shaped peaks with offset m/z values. The fractions of
      stable and metastable (M + 2H)+? ions and their mass shifts depend on the
      presence of Pro-4 and Leu-4 residues in the peptides, with the Pro-4 sequences
      giving larger fractions of the stable ions while showing smaller mass shifts for
      the metastables. Conversion of the Asp and C-terminal carboxyl groups to methyl
      esters further lowers the charge-reduced ion stability. Collisional activation
      and photodissociation at 355 nm of mass-selected (M + 2H)+? results in different
      dissociations that give sequence specific MS3 spectra. With a single exception of
      charge-reduced (LKGLADR + 2H)+?, the MS3 spectra do not produce ETD sequence
      fragments of the c and z type. Hence, these (M + 2H)+? ions are covalent
      radicals, not ion-molecule complexes, undergoing dramatically different
      dissociations in the ground and excited electronic states. The increased
      stability of the Pro-4 containing (M + 2H)+? ions is attributed to radicals
      formed by opening of the Pro ring and undergoing further stabilization by
      hydrogen atom migrations. UV-VIS photodissociation action spectroscopy and time
      dependent density functional theory calculations are used in a case in point
      study of the stable (LKGPADR + 2H)+? ion produced by ETD. In contrast to singly
      reduced peptide ions, doubly reduced (M + 3H)+ ions are stable only when formed
      from the Pro-4 precursors and show all characteristics of even electron ions
      regarding no photon absorption at 355 nm or ion-molecule reactions, and
      exhibiting proton driven collision induced dissociations. Graphical Abstract ?.

PMID- 27709511
TI  - Quantitation of the Noncovalent Cellular Retinol-Binding Protein, Type 1 Complex
      Through Native Mass Spectrometry.
AB  - Native mass spectrometry (MS) has become a valuable tool in probing noncovalent
      protein-ligand interactions in a sample-efficient way, yet the quantitative
      application potential of native MS has not been fully explored. Cellular retinol
      binding protein, type I (CrbpI) chaperones retinol and retinal in the cell,
      protecting them from nonspecific oxidation and delivering them to biosynthesis
      enzymes where the bound (holo-) and unbound (apo-) forms of CrbpI exert distinct
      biological functions. Using nanoelectrospray, we developed a native MS assay for
      probing apo- and holo-CrbpI abundance to facilitate exploring their biological
      functions in retinoid metabolism and signaling. The methods were developed on two
      platforms, an Orbitrap-based Thermo Exactive and a Q-IMS-TOF-based Waters Synapt
      G2S, where similar ion behaviors under optimized conditions were observed.
      Overall, our results suggested that within the working range (~1-10 MUM), gas
      phase ions in the native state linearly correspond to solution concentration and
      relative ion intensities of the apo- and holo-protein ions can linearly respond
      to the solution ratios, suggesting native MS is a viable tool for relative
      quantitation in this system. Graphical Abstract ?.

PMID- 27709512
TI  - Neural correlates of immediate and prolonged effects of cognitive reappraisal and
      distraction on emotional experience.
AB  - Cognitive emotion regulation strategies are important components of cognitive
      behavioral therapy (CBT). Additionally, up-regulation and difficulties in the
      down-regulation of negative feelings are associated with mental disorders.
      However, little is known about the lasting effects of cognitive emotion
      regulation strategies on emotional experience and associated neural activation.
      Therefore, this study investigated immediate and prolonged effects of emotion
      regulation using cognitive reappraisal and distraction on subjective report and
      its neural correlates. Twenty-seven healthy females took part in a 2-day
      functional magnetic resonance imaging study. They were instructed to either up
      regulate or down-regulate their negative feelings using a situation-focused
      cognitive reappraisal strategy, to distract themselves by imagining a specific
      neutral situation, or to passively look at repeatedly presented aversive and
      neutral pictures. Re-exposure to the same stimuli without a regulation
      instruction was conducted one day later. Self-reported negative feelings and
      blood-oxygen-level-dependent responses served as main outcome variables. As
      expected, the results show successful immediate up- or down-regulation of
      negative feelings by cognitive reappraisal and down-regulation of negative
      feelings by distraction. Furthermore, these changes in negative feelings were
      correlated with amygdala activation. A lasting effect on emotional experience
      associated with stronger ventromedial prefrontal cortex activation was found for
      down-regulation of negative feelings via cognitive reappraisal. Compared to
      distraction, down-regulation via cognitive reappraisal led to reduced negative
      feelings and stronger dorso- and ventrolateral prefrontal cortex responses one
      day later. While cognitive reappraisal and distraction are both effective
      strategies during active regulation, only cognitive reappraisal had a lasting
      effect. These findings might have implications for CBT.

PMID- 27709521
TI  - IDA urges ILA to review and clarify key points in dyslexia research advisory.

PMID- 27709513
TI  - Resting-state global functional connectivity as a biomarker of cognitive reserve
      in mild cognitive impairment.
AB  - Cognitive reserve (CR) shows protective effects in Alzheimer's disease (AD) and
      reduces the risk of dementia. Despite the clinical significance of CR, a
      clinically useful diagnostic biomarker of brain changes underlying CR in AD is
      not available yet. Our aim was to develop a fully-automated approach applied to
      fMRI to produce a biomarker associated with CR in subjects at increased risk of
      AD. We computed resting-state global functional connectivity (GFC), i.e. the
      average connectivity strength, for each voxel within the cognitive control
      network, which may sustain CR due to its central role in higher cognitive
      function. In a training sample including 43 mild cognitive impairment (MCI)
      subjects and 24 healthy controls (HC), we found that MCI subjects with high CR (>
      median of years of education, CR+) showed increased frequency of high GFC values
      compared to MCI-CR- and HC. A summary index capturing such a surplus frequency of
      high GFC was computed (called GFC reserve (GFC-R) index). GFC-R discriminated MCI
      CR+ vs. MCI-CR-, with the area under the ROC = 0.84. Cross-validation in an
      independently recruited test sample of 23 MCI subjects showed that higher levels
      of the GFC-R index predicted higher years of education and an alternative
      questionnaire-based proxy of CR, controlled for memory performance, gray matter
      of the cognitive control network, white matter hyperintensities, age, and gender.
      In conclusion, the GFC-R index that captures GFC changes within the cognitive
      control network provides a biomarker candidate of functional brain changes of CR
      in patients at increased risk of AD.

PMID- 27709529
TI  - Dose-related effects of succinylcholine on the adductor pollicis and masseter
      muscles in children.
AB  - This study was performed to determine the effects of various doses of
      succinylcholine on resting tension and evoked twitch height at the masseter and
      adductor pollicis muscles in children. Twenty patients, aged 3-10yr, ASA physical
      status I or II, were randomly assigned to receive succinylcholine 0.15, 0.25,
      0.50 or 1.00 mg . kg-1, during halothane-nitrous oxide anaesthesia. Supramaximal
      train-of-four stimulation was applied simultaneously to the ulnar nerve and the
      nerve to the masseter. Transducers recorded force at the jaw and the thumb.
      Maximum blockade of the first twitch (T1) and maximum resting tension change were
      measured. Potency of succinylcholine at the two muscles was estimated by linear
      regression of the logit transformation of T1 versus log dose. The relationship
      between resting tension change and log dose was established by linear regression.
      The masseter muscle was more sensitive to succinylcholine than the adductor
      pollicis with an ED95 of 0.28 +/- 0.02 (mean +/-SEM) vs 0.44 +/- 0.05 mg . kg-1
      (P < 0.05). Onset of neuromuscular blockade was faster at the masseter, and
      recovery occurred simultaneously in both muscles. A dose-related increase in
      resting tension was observed in both muscles, but its magnitude was five times
      greater at the masseter. With succinylcholine, 1 mg . kg-1, this increase was
      51.6 +/- 16.8 g at the masseter and 9.1 +/- 2.3 g at the adductor pollicis.
      Tension returned to baseline within 1-2 min. It is concluded that in children (1)
      succinylcholine produces dose-related changes in resting tension; (2) this
      effect, although quantitatively important at the masseter, is not restricted to
      that muscle; and (3) relatively small doses of succinylcholine are required to
      block neuromuscular transmission at the jaw.

PMID- 27709522
TI  - Adult pulmonary tuberculosis as a pathological manifestation of hyperactive
      antimycobacterial immune response.
AB  - The intricate relationship between tuberculosis (TB) and immune system remains
      poorly understood. It is generally believed that weakening of the immune response
      against Mycobacterium tuberculosis leads to reactivation of latent infection into
      the active pulmonary disease. However, heterogeneous nature of TB and failure of
      rationally designed vaccines in clinical trials raises serious questions against
      the simplistic view of TB as an outcome of weakened immunity. In the wake of
      accumulating human TB data, it is argued here that a hyperactive
      antimycobacterial immune response is to blame for the pathogenesis of pulmonary
      TB in immunocompetent adults. Direct and indirect evidence supporting this notion
      is presented in this article. Revisiting the role of immune system in TB
      pathogenesis will pave the way for effective anti-TB vaccines.

PMID- 27709523
TI  - Serum levels of S100A6 are unaltered in patients with resectable
      cholangiocarcinoma.
AB  - BACKGROUND: Elevated expression levels of S100A6, a calcium-binding low-molecular
      weight protein, were demonstrated in various malignancies. Moreover, increased
      serum levels of S100A6 were suggested as a novel biomarker for various
      inflammatory and malignant diseases including lung and gastric cancer. However,
      up to now, serum concentrations of S100A6 have not been analyzed in patients with
      cholangiocarcinoma (CCA). METHODS: S100A6 mRNA expression levels were analyzed in
      human and murine CCA tumor samples, using semi-quantitative reverse transcriptase
      PCR. S100A6 serum concentrations were measured using an enzyme-linked
      immunosorbent assay in 112 patients with CCA referred to surgery for curative
      resection and were compared to those of 42 healthy controls. Results were
      correlated with clinical data. RESULTS: S100A6 mRNA expression levels were
      significantly up-regulated in tumor samples of CCA patients and in tumor tissue
      of a CCA mouse model. In contrast, serum levels of S100A6 were not significantly
      altered in patients with CCA compared to healthy controls. Whereas no differences
      became apparent within the different clinical subgroups of CCA, patients with
      primary sclerosing cholangitis (PSC)-based CCA displayed higher levels of S100A6
      compared to the other patients. Nevertheless, patients with higher S100A6 serum
      concentrations showed a trend towards an impaired prognosis compared to patients
      with lower levels. Finally, within our cohort of patients both the diagnostic and
      prognostic potentials of S100A6 were similar to those of the clinically
      established biomarkers CEA and CA19-9. CONCLUSION: Although S100A6 was expressed
      at significantly higher levels in human and murine CCA tumor samples, S100A6
      serum levels were not regulated in patients with CCA and are thus not suitable
      for diagnosis of CCA. However, CCA-patients with elevated S100A6 displayed a
      trend toward an impaired prognosis compared to patients with lower S100A6 levels,
      supporting its further evaluation as a prognostic biomarker in CCA.

PMID- 27709530
TI  - Jaw muscle tension after succinychloline in children undergoing strabismus
      surgery.
AB  - The increases in tension at the masseter and adductor pollicis muscles following
      succinylcholine, 1 mg . kg-1, during halothane anaesthesia were measured in eight
      children, 3-10 yr, with strabismus. The results were compared with those obtained
      in a control group of general surgical patients. Supramaximal train-of-four (TOF)
      stimulation was applied to the ulnar nerve and the nerve to the masseter
      simultaneously. Jaw closure was measured by a force transducer system. In all
      patients, succinylcholine caused an increase in resting tone at the jaw and at
      the thumb. In the strabismus group, the magnitude of this increase was 55.7 +/
      23.2 g, mean +/-SD, at the jaw and 11.3 +/-5.6 g at the thumb. This was not
      significantly different from the values obtained in controls, 45.3 +/-33.4 g and
      7.9 +/-4.2 g, respectively. The duration of the phenomenon was 1-2 min in both
      muscles studied, and was not statistically different in the strabismus group.
      Time to complete neuromuscular blockade was significantly faster at the masseter,
      31 +/-6 sec -control groups; 39 +/-11 sec -strabismus group, than at adductor
      pollicis, 61 +/-34 sec -control groups; 75 +/-28 sec -strabismus group (P < 0.05
      and 0.013 respectively). It is concluded that succinylcholine causes similar
      increases in jaw tension and comparable degrees of neuromuscular blockade in
      patients undergoing strabismus surgery as in other children.

PMID- 27709531
TI  - Modifications hemodynamiques durant la coelioscopie: etude menee par bioimpedance
      electrique thoracique.
AB  - Au cours de 18 coelioscopies chez des jeunes femmes A.S.A. status physique 1, les
      consequences hemodynamiques du pneumoperitoine et de la position de Trendelenburg
      ont ete evaluees par la methode non invasive de bioimpedance electrique
      thoracique. L'index cardiaque chute significativement de 3,2 a 2,8 L . min-1 . m
      2 a l'insufflation intra-abdominale et retrouve ses valeurs de depart apres dix
      minutes de Trendelenburg. La pression arterielle moyenne et les resistances
      vasculaires systemiques indexees sont tres augmentees de 1620 a 2491 dyn . s . cm
      5 . m-2 apres insufflation; l'exsufflation ne permet pas un retour aux valeurs de
      depart: l'elevation residuelle des RVSI est de 30 pour cent. L'obstacle au retour
      veineux pas compression intra-abdominale explique bien la chute du debit
      cardiaque, conformement aux donnees de la litterature. En revanche,
      l'augmentation des resistances vasculaires systemiques ne peut etre expliquee par
      les seuls phenomenes mecaniques du fait de leur persistance apres la levee de la
      compression. L'hypothese de l'intervention d'un mediateur humoral doit done etre
      discutee.In 18 women A.S.A. physical status 1, a noninvasive thoracic electrical
      bioimpedance method was used to evaluate haemodynamic changes during
      gynaecologycal laparoscopy. A significant decrease in cardiac index was observed
      after peritoneal insufflation, from 3.2 to 2.8 L . min-1 . m-2 and returned to
      the initial values after ten minutes of Trendelenburg's position. Elevated intra
      abdominal pressure was also associated with a significant increase in mean
      arterial pressure (from 68 to 88 mmHg) and systemic vascular resistance index
      (from 1620 to 2491 dyn . s . cm-5 . m-2). However, values were not restored after
      peritoneal exsufflation: systemic vascular resistance index values remained 30
      per cent higher than that before insufflation. Decreased venous return may
      account for the significant decrease in cardiac output but mechanical compression
      does not explain the persistent elevation of systemic vascular resistance.

PMID- 27709533
TI  - Advances in oral anti arrhythmic therapy: implications for the anaesthetist.
AB  - Surgical patients often are receiving antiarrhythmic therapy. Thus, because
      anaesthetic agents can affect cardiac function and may interact with concurrent
      antiarrhythmic medications, the anaesthetist should be aware of the
      electrophysiology associated with dysrhythmias and their management. Tocainide,
      flecainide, mexiletine, encainide and amiodarone have been introduced recently
      and each has an unique pattern of bioavailability, metabolism and toxicity.
      Patients treated with these drugs need special concern as they have abnormal
      cardiovascular systems and may be at increased risk for perioperative morbidity.
      In addition, unexpected untoward reactions and toxicity can result from
      interactions of anaesthetic agents and these drugs. This review discusses normal
      cardiac electrophysiology, common dysrhythmias and the electrophysiological
      effects of the newer oral antiarrhythmic drugs.

PMID- 27709532
TI  - Esmolol bolus and infusion attenuates increases in blood pressure and heart rate
      during electro-convulsive therapy.
AB  - To determine whether a standardized dose of esmolol can effectively attenuate the
      cardiovascular response to electroconvulsive therapy (ECT), 17 ASA physical
      status I-II patients were studied in a randomized within-patient, crossover
      design. Each patient received "no esmolol" during one ECT and three to five days
      later crossed over to the alternative treatment receiving an esmolol 80 mg bolus
      followed by 24 mg . min-1 infusion two minutes prior to induction of anaesthesia
      and continued for five minutes after induction. Esmolol blunted the maximum
      increases in heart rate (HR) by 26 per cent, mean arterial pressure (MAP) by 14
      per cent, and rate pressure product by 37 per cent with significant differences
      (P < 0.05) noted at one, two, three and four minutes after ECT (minutes five,
      six, seven, and eight of the esmolol infusion). There was no significant
      difference in seizure duration between the two groups and no adverse reactions
      occurred.

PMID- 27709534
TI  - A simple solution to blood clot obstruction opepidural catheter during labour.

PMID- 27709539
TI  - [The agar diffusion method. Round table discussion on the methods and indications
      for determining blood levels of aminoglycosides].
AB  - The present-day technique of determining the concentration of aminoglycosides in
      blood by agar diffusion is described including the apparatuses, set-up, and
      reliability tests. The results of comparative investigations showed a higher
      degree of conformity in Mueller-Hinton agar than in standard agar. Due to its
      accuracy the agar diffusion method is especially suited for the calculation of
      dosage recommendations and for the prediction of the maximal and minimal blood
      levels during treatment with aminoglycosides.

PMID- 27709537
TI  - Impact of preprocedural atrial fibrillation on immediate and long-term outcomes
      after successful percutaneous mitral valvuloplasty of significant mitral
      stenosis.
AB  - Optimal time to perform percutaneous mitral valvuloplasty (PMV) for patients with
      significant mitral stenosis (MS) and atrial fibrillation (AF) remains
      controversial. We sought to identify prognostic factors and evaluate long-term
      clinical outcomes after PMV of 77 consecutive patients with MS with a mitral
      valve area (MVA) <1.5 cm2. According to baseline heart rhythm, these patients
      were divided into sinus rhythm (SR; n = 24) and AF (n = 53) groups. The study
      endpoint was defined as a composite of all-cause mortality, admission for heart
      failure, mitral valve surgery, repeated PMV, and major cerebral vascular accident
      during follow-up. After successful PMV, there was no significant difference
      between the two groups in post-MVA and post-mitral mean pressure gradient.
      However, the New York Heart Association Functional Classification post-procedure
      was worse in the AF group (p < 0.01). In the AF group, event-free survival during
      follow-up was significantly lower compared with that of the SR group (p = 0.016).
      Independent predictors of clinical events were AF [hazard ratio (HR), 2.73; 95 %
      confidence interval (CI), 1.04-9.36; p = 0.03] and pulmonary artery systolic
      pressure (HR 2.57; 95 % CI 1.18-5.47; p = 0.017). Patients with AF at baseline
      were significantly associated with worse symptoms and higher event rates after
      successful PMV compared with those with SR. The clinical benefit of PMV may be
      considered for patients with MVA <1.5 cm2 before the onset of AF.

PMID- 27709540
TI  - [Microbiological diagnosis of septicemia].
AB  - To detect microorganisms in the blood it is necessary not only that the
      microbiologist uses reliable methods, but also that the clinician takes a
      sufficient number of blood samples at the right point in time using a correct
      method for drawing the blood. The best results are obtained if the blood sample
      is transferred to the culture media at the bedside. The media should contain
      anticoagulants, osmosis stabilizers and preparations to neutralize the microbial
      action of the blood (caused by intrinsic and extrinsic factors). Up until now
      sodium polyanetholsulfonate ("Liquoid") has proved to be the most suitable
      additive. The procedure used for blood culturing must enable growth of aerobes,
      anaerobes and microbes with cell-wall damage. Today, modern methods such as
      radiometry, impedance measurement and microcalorimetry are used or are in the
      process of being developed which facilitate screening for positive cultures.
      Antigens, cell-wall constituents and metabolites of bacteria and fungi present in
      the blood stream can be detected by means of counter-immunoelectrophoresis, the
      Limulus test and gas chromatography, without culturing being necessary.
      Concentration techniques such as filtration and centrifugation are also being
      refined to enable a more reliable and earlier detection of septicemia.

PMID- 27709544
TI  - Evaluation and Elucidation Studies of Natural Aglycones for Anticancer Potential
      using Apoptosis-Related Markers: An In silico Study.
AB  - Exposure to exogenous and endogenous chemicals and subsequent cellular and
      molecular changes has been linked to enhanced cell proliferation and restricted
      apoptosis phenomenon. Though in the past decades numerous anticancer drugs
      inducing programmed cell death in cancer cells by targeting specific apoptotic
      markers have reached the market, they have been allied with unwanted side
      effects, ranging from mild to severe toxicity. With further understanding on the
      functional mechanism of p53 and MDM2 in apoptosis and in our continuous search
      for new and potent multi-target anticancer lead compounds, we have carried out
      molecular docking and inhibition studies of the selected aglycones along with
      selected anticancer leads, against the specific apoptotic and cell cycle markers
      using AutoDock Tools 4.0 and other computational softwares. The docking results
      have been analyzed in terms of binding energies (kcal/mol) and inhibition
      constant (uM). The study clearly proposes our aglycones [solanidine (Solanid-5-en
      3beta-ol), solasodine (Solasod-5-en-3beta-ol), and tomatidine (5alpha-Tomatidan
      3beta-ol)] induce apoptosis by inhibiting the p53-MDM2 complex, p21Waf1/Cip1, and
      Bcl-2 proteins, which were even found comparable with the anticancer drugs nutlin
      and/or halofuginone. The work further emphasizes that the individual molecular
      targets such as BAX and Bcl-2 may result in misleading data at any level;
      however, ratio of responses to BAX and Bcl-2 shall be considered for better clue
      about a compound to be pro- or anti-apoptotic.

PMID- 27709545
TI  - Hepatosplenic candidasis, a fatal disease?
AB  - We report on two patients with acute leukemia and prolonged granulocytopenia
      after cytotoxic therapy in whom the diagnosis hepatosplenic candidiasis was made.
      Both patients developed upper abdominal discomfort with elevated alkaline
      phosphatase after resolution of granulocytopenia. The diagnosis was established
      by demonstration of multiple abscesses in liver and spleen on ultrasound and
      computed tomography. Both patients were initially treated with amphotericin B
      i.v., one of them received liposomal amphotericin B (cumulative dose of 2,530 mg
      and 570 mg, respectively). Thereafter, therapy was continued for months with oral
      fluconazole. The treatment of hepatosplenic candidiasis was successful, however,
      the patients died from relapse and progression of leukemia.

PMID- 27709547
TI  - Rapid total volatile organic carbon quantification from microbial fermentation
      using a platinum catalyst and proton transfer reaction-mass spectrometry.
AB  - A novel analytical system was developed to rapidly and accurately quantify total
      volatile organic compound (VOC) production from microbial reactor systems using a
      platinum catalyst and a sensitive CO2 detector. This system allows nearly
      instantaneous determination of total VOC production by utilizing a platinum
      catalyst to completely and quantitatively oxidize headspace VOCs to CO2 in
      coordination with a CO2 detector. Measurement of respiratory CO2 by bypassing the
      catalyst allowed the total VOC content to be determined from the difference in
      the two signals. To the best of our knowledge, this is the first instance of a
      platinum catalyst and CO2 detector being used to quantify the total VOCs produced
      by a complex bioreactor system. Continuous recording of these CO2 data provided a
      record of respiration and total VOC production throughout the experiments. Proton
      transfer reaction-mass spectrometry (PTR-MS) was used to identify and quantify
      major VOCs. The sum of the individual compounds measured by PTR-MS can be
      compared to the total VOCs quantified by the platinum catalyst to identify
      potential differences in detection, identification and calibration. PTR-MS
      measurements accounted on average for 94 % of the total VOC carbon detected by
      the platinum catalyst and CO2 detector. In a model system, a VOC producing
      endophytic fungus Nodulisporium isolate TI-13 was grown in a solid state reactor
      utilizing the agricultural byproduct beet pulp as a substrate. Temporal changes
      in production of major volatile compounds (ethanol, methanol, acetaldehyde,
      terpenes, and terpenoids) were quantified by PTR-MS and compared to the total VOC
      measurements taken with the platinum catalyst and CO2 detector. This analytical
      system provided fast, consistent data for evaluating VOC production in the
      nonhomogeneous solid state reactor system.

PMID- 27709546
TI  - Phantom criteria for qualification of brain FDG and amyloid PET across different
      cameras.
AB  - BACKGROUND: While fluorodeoxyglucose (FDG) and amyloid PET is valuable for
      patient management, research, and clinical trial of therapeutics on Alzheimer's
      disease, the specific details of the PET scanning method including the PET camera
      model type influence the image quality, which may further affect the
      interpretation of images and quantitative capabilities. To make multicenter PET
      data reliable and to establish PET scanning as a universal diagnostic technique
      and a verified biomarker, we have proposed phantom test procedures and criteria
      for optimizing image quality across different PET cameras. RESULTS: As the
      method, four physical parameters (resolution, gray-white contrast, uniformity,
      and image noise) were selected as essential to image quality for brain FDG and
      amyloid PET and were measured with a Hoffman 3D brain phantom and a uniform
      cylindrical phantom on a total of 12 currently used PET models. The phantom
      radioactivity and acquisition time were determined based on the standard scanning
      protocol for each PET drug (FDG, 11C-PiB, 18F-florbetapir, and 18F-flutemetamol).
      Reconstruction parameters were either determined based on the methods adopted in
      ADNI, J-ADNI, and other research and clinical trials or optimized based on
      measured phantom image parameters under various reconstruction conditions. As the
      result, phantom test criteria were proposed as follows: (i) 8 mm FWHM or better
      resolution and (ii) gray/white %contrast >=55 % with the Hoffman 3D brain phantom
      and (iii) SD of 51 small region of interests (ROIs) <=0.0249 (equivalent to 5 %
      variation) for uniformity and (iv) image noise (SD/mean) <=15 % for a large ROI
      with the uniform cylindrical phantom. These criteria provided image quality
      conforming to those multicenter clinical studies and were also achievable with
      most of the PET cameras that are currently used. CONCLUSIONS: The proposed
      phantom test criteria facilitate standardization and qualification of brain FDG
      and amyloid PET images and deserve further evaluation by future multicenter
      clinical studies.

PMID- 27709548
TI  - Cancer/testis antigens as molecular drug targets using network pharmacology.
AB  - Present chemotherapeutic drugs have limited efficacy and severe side effects.
      Considering the complexity of cancer, an effective strategy is necessary to
      discover multiple new drug targets. Cancer/testis antigens are vital for cancer
      cell progression. We have performed a computational network analysis of
      cancer/testis antigens and assessed these antigens as drug targets. During this
      analysis, protein interaction network of 700 human CT antigens was investigated.
      CT antigen network consisted of eight independent components. Four major hubs and
      two minor hubs were identified that play nodal role in the flow of information
      across the largest network. We have predicted 30 potential drug targets by
      analysing several topological parameters such as betweenness centrality, cluster
      coefficient and probable protein complexes. Structural and functional roles of
      potential drug targets have also been anatomized. Analysis of the CT antigen
      network enables us to pinpoint a set of candidate proteins that if targeted could
      be detrimental for cancerous cell without affecting any normal cell. The list of
      putative proteins is a starting point for experimental validation and may help
      further in the discovery of new anticancer drug targets.

PMID- 27709549
TI  - Reversal effect of ouabain on multidrug resistance in esophageal carcinoma
      EC109/CDDP cells by inhibiting the translocation of Wnt/beta-catenin into the
      nucleus.
AB  - The incidence of esophageal carcinoma is increasing throughout the world. A major
      obstacle to its treatment is acquired multidrug resistance (MDR) which results in
      the failure of chemotherapy and patient relapse. Here, we identified that ouabain
      is capable of reversing MDR to cisplatin (CDDP) in EC109/CDDP cells and explore
      the possible mechanisms of action. The parental and the MDR cell lines were both
      sensitive to ouabain with 50 % inhibitory concentration (IC50) values of 258.11
      and 710.63 nM, respectively. Cisplatin cytotoxicity increased in the EC109/CDDP
      cells by the addition of ouabain which helps promote CDDP-induced apoptosis.
      Ouabain at 20 nM effectively reduced the IC50 of CDDP in EC109/CDDP cells from
      36.54 to 3.39 MUM. This represents a 10.78-fold increase in sensitization to
      CDDP. We also found that ouabain was capable of down regulating the expression of
      P-glycoprotein (P-gp) and Bcl-2 in a dose- and time-dependent manner. Finally,
      the results indicated that ouabain suppressed Wnt luciferase report (TOPFlash)
      activity obviously in EC109/CDDP and depressed the translocation of beta-catenin
      into the nucleus. Moreover, ouabain showed reversal effect of MDR to CDDP in nude
      mouse xenograft model, and reduced the protein level of beta-catenin (Y333) in
      tumor tissue of CDDP plus ouabain group. All data proved that ouabain has a
      potent beta-catenin-dependent anti-MDR effect.

PMID- 27709550
TI  - CD4+ T cell-mediated cytotoxicity eliminates primary tumor cells in metastatic
      melanoma through high MHC class II expression and can be enhanced by inhibitory
      receptor blockade.
AB  - Metastatic melanoma is a rapidly progressing disease with high mortality rate and
      limited treatment options. Immunotherapy based on tumor-targeting cytotoxic T
      cell responses represents a promising strategy. To assist in its development, we
      examined the possibility and efficacy of using CD4+ cytotoxic T cells. The
      regulatory mechanisms controlling CD4+ T cell-mediated cytotoxicity were also
      investigated. We found that naturally occurring granzyme B and perforin
      expressing CD4+ cytotoxic T cells can be recovered from metastatic melanoma
      patients at significantly elevated frequencies compared to those from healthy
      controls. These CD4+ cytotoxic T cells were also capable of killing autologous
      tumor cells harvested from metastatic melanoma, independent of CD8+ T cells or
      any other cell types. However, several restricting factors were observed. First,
      the cytolytic activity by CD4+ T cells required high MHC class II expression on
      melanoma cells, which was not satisfied in a subset of melanomas. Second, the
      granzyme B and perforin release by activated CD4+ cytotoxic T cells was reduced
      after coculturing with autologous melanoma cells, characterized by low LAMP-1
      expression and low granzyme B and perforin secretion in the supernatant. This
      suggested that inhibitory mechanisms were present to suppress CD4+ cytotoxic T
      cells. Indeed, blockade of PD-1 and CTLA-4 had increased the cytolytic activity
      of CD4+ T cells but was only effective in MHC class II high but not MHC class II
      low melanomas. Together, our study showed that CD4+ T cell-mediated cytotoxicity
      could eliminate primary melanoma cells but the efficacy depended on MHC class II
      expression.

PMID- 27709551
TI  - Serum levels of apolipoprotein E correlates with disease progression and poor
      prognosis in breast cancer.
AB  - ApoE has been reported to be associated with tumorigenesis and tumor progression.
      In this study, we explored the potential diagnostic and prognostic role of serum
      ApoE in breast cancer patients. Subject cohorts consisted of 152 normal healthy
      controls female and 257 breast cancer cases. Serum levels of ApoE were determined
      with turbidimetric immunoassay. The serum levels of ApoE were significantly
      elevated in breast cancer patients compared with normal healthy controls (45.82
      +/- 13.96 mg/L vs. 33.61 +/- 6.44 mg/L, respectively, P < 0.0001) and also
      significantly associated with TNM stage and lymph nodes status (all P < 0.05).
      Area under receiver operating characteristic curve for serum ApoE discriminate
      breast cancer patients from controls was 0.786 with specificity of 0.974 and
      sensitivity of 0.541, the cut-off value of ApoE was 43.15 mg/L. Kaplan-Meier log
      rank analysis showed that the high serum ApoE group (serum ApoE >= 43.15 mg/L)
      had a poorer progression-free survival and overall survival compared with low
      serum ApoE group (serum ApoE < 43.15 mg/L) (all P < 0.05). In addition,
      univariate and multivariate Cox regression analysis displayed serum ApoE as an
      independent risk factor of breast cancer patients prognosis (all P < 0.05). Serum
      ApoE played a role as serological biomarkers that indicated diagnostic and
      prognostic evaluation in breast cancer patients.

PMID- 27709552
TI  - A new ten-gene risk fraction model serving as prognostic indicator for clinical
      outcome of multiple myeloma.
AB  - Multiple myeloma (MM) is a kind of aggressive tumor prevalent with high
      heterogeneity. Abnormal expression of certain genes may lead to the occurrence
      and development of MM. Nowadays, it is not commonly seen in clinical research to
      predict the prognostic circumstances of patients with MM by multiple gene
      expression profiling method. Identification of potential genes in prognostic
      process could be beneficial for clinical management of MM. Therefore, we aimed to
      build a risk fraction model to screen out the prognostic indicator for clinical
      outcome of MM. Microarray data were downloaded from the Genome Expression Omnibus
      (GEO) datasets with accession numbers GSE24080 and GSE57317. A total of 279
      samples were selected out randomly. Besides, a risk formula was constructed and
      verified in the dataset. Time-dependent receiver operating characteristic (ROC)
      curve was applied in evaluating the accurate prognostic conditions of patients.
      Finally, a ten genes model in the training dataset was found to be closely
      related to the survival condition of MM patients. Patients with MM were divided
      into two groups, high-risk and low-risk, by the expression of these ten genes,
      and significant statistical difference was found between the two groups.
      Furthermore, the result of multivariate cox regression and stratified analysis
      indicated that this model was independent of other clinical phenotypes. ROC
      curves also showed its feasibility to predict the survival status of MM patients.
      Our results demonstrated that the fraction risk model constructed by the selected
      ten genes could be used to predict survival status of multiple myeloma patients,
      which could also help in improvement of prognostic and therapeutic tool of MM.

PMID- 27709553
TI  - Long noncoding RNA expression profile of infantile hemangioma identified by
      microarray analysis.
AB  - Infantile hemangioma (IH) is one of the most common vascular tumors of childhood.
      Long noncoding RNAs (lncRNAs) play a critical role in angiogenesis, but their
      involvement in hemangioma remains unknown. This study aimed to assess the
      expression profiles of lncRNAs in IH and adjacent normal tissue samples,
      exploring the biological functions of lncRNAs as well as their involvement in IH
      pathogenesis. The lncRNA expression profiles were determined by lncRNA
      microarrays. A total of 1259 and 857 lncRNAs were upregulated and downregulated
      in IH, respectively, at a fold change cutoff of 2.0 (p < 0.05); in addition, 1469
      and 1184 messenger RNAs (mRNAs) were upregulated and downregulated, respectively
      (fold change cutoff of 2.0; p < 0.05). A total of 292 differentially expressed
      mRNAs were targeted by the lncRNAs with altered expression in hemangioma,
      including 228 and 64 upregulated and downregulated, respectively (cutoff of 2.0,
      p < 0.05). Gene ontology (GO) analyses revealed several angiogenesis-related
      pathways. An lncRNA-mRNA co-expression network for differentially expressed
      lncRNAs revealed significant associations of the lncRNAs MEG3, MEG8, FENDRR, and
      Linc00152 with their related mRNAs. The validation results of nine differentially
      expressed lncRNAs (MALAT1, MEG3, MEG8, p29066, p33867, FENDRR, Linc00152,
      p44557_v4, p8683) as well as two mRNAs (FOXF1, EGFL7) indicated that the
      microarray data correlated well with the QPCR results. Interestingly, MALAT1
      knockdown induced apoptosis and S-phase cell cycle arrest in human umbilical vein
      endothelial cells (HUVECs). Overall, this study revealed the lncRNA expression
      profile of IH and that lncRNAs likely regulate several genes with important roles
      in angiogenesis.

PMID- 27709554
TI  - The Role of Ultrasound on Advanced Oxidation Processes.
AB  - This chapter describes the use of ultrasound in remediation of wastewater
      contaminated with organic pollutants in the absence and presence of other
      advanced oxidation processes (AOPs) such as sonolysis, sono-ozone process,
      sonophotocatalysis, sonoFenton systems and sonophoto-Fenton methods in detail.
      All these methods are explained with the suitable literature illustrations. In
      most of the cases, hybrid AOPs (combination of ultrasound with one or more AOPs)
      resulted in superior efficacy to that of individual AOP. The advantageous effects
      such as additive and synergistic effects obtained by operating the hybrid AOPs
      are highlighted with appropriate examples. It is worth to mention here that the
      utilization of ultrasound is not only restricted in preparation of modern active
      catalysts but also extensively used for the wastewater treatment. Interestingly,
      ultrasound coupled AOPs are operationally simple, efficient, and environmentally
      benign, and can be readily applied for large scale industrial processes which
      make them economically viable.

PMID- 27709556
TI  - Prognosis of cirrhotic patients admitted to the general ICU.
AB  - BACKGROUND: The prognosis of cirrhotic patients admitted to the ICU is considered
      to be poor but has been mainly reported in liver ICU. We aimed to describe the
      prognosis of cirrhotic patients admitted to a general ICU, to assess the
      predictors of mortality in this population, and, finally, to identify a subgroup
      of patients in whom intensive care escalation might be discussed. RESULTS: We
      performed a retrospective monocentric study of all cirrhotic patients
      consecutively admitted between 2002 and 2014 in a general ICU in a regional
      university hospital. Two hundred and eighteen cirrhotic patients were admitted to
      the ICU. The 28-day and 6-month mortality rates were 53 and 74 %, respectively.
      Among the 115 patients who were discharged from ICU, only eight patients
      underwent liver transplantation, whereas 48 had no clear contraindication.
      Multivariable analyses on 28-day mortality identified three independent
      variables, incorporated into a new three-variable prognostic model as follows:
      SOFA >= 12 (OR 4.2 [2.2-8.0]; 2 points), INR >= 2.6 (OR 2.5 [1.3-4.8]; 1 point),
      and renal replacement therapy (OR 2.3 [1.1-5.1]; 1 point). For a value of the
      score at 4 (16 % of patients), 28-day and 3-month mortality rates were 91 and 100
      %, respectively. An external validation of the score among 149 critically ill
      cirrhotic patients showed a good accuracy for predicting in-ICU mortality.
      CONCLUSIONS: Mortality of cirrhotic patients admitted to a general ICU was
      comparable to that of other studies. A pragmatic score integrating the SOFA
      score, INR, and the need for extrarenal epuration was strongly associated with
      mortality. Among the 16 % of patients presenting with score 4 at ICU admission,
      100 % died in the 3-month follow-up period. The prognostic evaluation on day 3
      remains essential for the majority of patients. However, this score calculable at
      ICU admission might identify patients in whom the benefit of intensive care
      escalation should be discussed, in particular when liver transplantation is
      contraindicated.

PMID- 27709555
TI  - Post-Concussive Syndrome: a Focus on Post-Traumatic Headache and Related
      Cognitive, Psychiatric, and Sleep Issues.
AB  - PURPOSE OF REVIEW: Post-traumatic headache (PTH) is a secondary headache disorder
      following traumatic brain injury. We sought to examine the recent literature on
      PTH and associated cognitive, psychiatric, and sleep conditions to understand the
      latest findings about the associated conditions and available screening tools,
      and to understand the available treatment options for PTH. RECENT FINDINGS: Up to
      one third of PTH patients may have depression and about one quarter may have
      insomnia. Anxiety and cognitive issues are also common. While there are few
      studies examining abortive medications for PTH, recent studies of preventive
      medications examine the efficacy of topiramate, and topiramate may be better than
      other oral preventive medications. Other currently investigated treatments
      include nerve blocks, onabotulinum toxin A, transmagnetic stimulation, and
      behavioral therapy (biofeedback). Due to an expanded focus on and knowledge of
      concussion and PTH, comorbid psychiatric, cognitive, and sleep issues have become
      more widely acknowledged and studied. However, more high-quality studies must be
      conducted to examine the underlying pathophysiology of PTH and associated
      symptoms and to determine the most effective abortive and preventive treatment
      options.

PMID- 27709557
TI  - Erythrocyte superoxide dismutase as a biomarker of septic acute kidney injury.
AB  - BACKGROUND: Oxidative stress is a key feature of sepsis and could be a common
      pathophysiological pathway between septic shock and acute kidney injury (AKI) Our
      objective was to evaluate the erythrocyte superoxide dismutase (SOD1) activity as
      predictor of AKI in patients with septic shock. METHODS: This is a prospective
      observational study that evaluated 175 consecutive patients over the age of 18
      years with septic shock upon intensive care unit (ICU) admission. However, 43
      patients were excluded (27 due to AKI at ICU admission). Thus, 132 patients were
      enrolled in the study. At the time of the patients' enrollment, demographic
      information was recorded. Blood samples were taken within the first 24 h of the
      patient's admission to determine the erythrocyte SOD1 activity. All patients were
      followed throughout the ICU stay, and the development of AKI was evaluated. In
      addition, we also evaluated 17 control subjects. RESULTS: The mean age of
      patients with septic shock was 63.2 +/- 15.7 years, 53 % were male and the median
      ICU stay was 8 days (4-16). Approximately 50.7 % developed AKI during the ICU
      stay. The median erythrocyte SOD1 activity was 2.92 (2.19-3.92) U/mg Hb. When
      compared to control subjects, septic shock patients had a higher serum
      malondialdehyde concentration and lower erythrocyte SOD1 activity. In univariate
      analysis, erythrocyte SOD1 activity was lower in patients who developed AKI. The
      ROC curve analysis revealed that lower erythrocyte SOD1 activity was associated
      with AKI development (AUC 0.686; CI 95 % 0.595-0.777; p < 0.001) at the cutoff of
      <3.32 U/mg Hb. In the logistic regression models, SOD1 activity higher than 3.32
      U/mg Hb was associated with protection of AKI development when adjusted by
      hemoglobin, phosphorus and APACHE II score (OR 0.309; CI 95 % 0.137-0.695; p =
      0.005) and when adjusted by age, gender, chronic kidney disease, admission
      category (medical or surgery) and APACHE II score (OR 0.129; CI 95 % 0.033-0.508;
      p = 0.003). CONCLUSIONS: In conclusion, our data suggest that erythrocyte SOD1
      activity could play a role as an early marker of septic AKI and could be seen as
      a new research avenue in the field of biomarker in AKI. However, our study did
      not show a strong correlation between SOD activity and AKI. Nevertheless, these
      original data do warrant further research in order to confirm or not this
      hypothesis.

PMID- 27709560
TI  - Biocompatible/Degradable Silk Fibroin:Poly(Vinyl Alcohol)-Blended Dielectric
      Layer Towards High-Performance Organic Field-Effect Transistor.
AB  - Biocompatible silk fibroin (SF):poly(vinyl alcohol) (PVA) blends were prepared as
      the dielectric layers of organic field-effect transistors (OFETs). Compared with
      those with pure SF dielectric layer, an optimal threshold voltage of ~0 V, high
      on/off ratio of ~104, and enhanced field-effect mobility of 0.22 cm2/Vs of OFETs
      were obtained by carefully controlling the weight ratio of SF:PVA blends to 7:5.
      Through the morphology characterization of dielectrics and organic semiconductors
      by utilizing atom force microscopy and electrical characterization of the
      devices, the performance improvement of OFETs with SF:PVA hybrid gate dielectric
      layers were attributed to the smooth and homogeneous morphology of blend
      dielectrics. Furthermore, due to lower charge carrier trap density, the OFETs
      based on SF:PVA-blended dielectric exhibited a higher bias stability than those
      based on pure SF dielectric.

PMID- 27709559
TI  - Pulsed Laser Ablation-Induced Green Synthesis of TiO2 Nanoparticles and
      Application of Novel Small Angle X-Ray Scattering Technique for Nanoparticle Size
      and Size Distribution Analysis.
AB  - This paper aims to introduce small angle X-ray scattering (SAXS) as a promising
      technique for measuring size and size distribution of TiO2 nanoparticles. In this
      manuscript, pulsed laser ablation in liquids (PLAL) has been demonstrated as a
      quick and simple technique for synthesizing TiO2 nanoparticles directly into
      deionized water as a suspension from titanium targets. Spherical TiO2
      nanoparticles with diameters in the range 4-35 nm were observed with transmission
      electron microscopy (TEM). X-ray diffraction (XRD) showed highly crystalline
      nanoparticles that comprised of two main photoactive phases of TiO2: anatase and
      rutile. However, presence of minor amounts of brookite was also reported. The
      traditional methods for nanoparticle size and size distribution analysis such as
      electron microscopy-based methods are time-consuming. In this study, we have
      proposed and validated SAXS as a promising method for characterization of laser
      ablated TiO2 nanoparticles for their size and size distribution by comparing SAXS
      and TEM-measured nanoparticle size and size distribution. SAXS- and TEM-measured
      size distributions closely followed each other for each sample, and size
      distributions in both showed maxima at the same nanoparticle size. The SAXS
      measured nanoparticle diameters were slightly larger than the respective
      diameters measured by TEM. This was because SAXS measures an agglomerate
      consisting of several particles as one big particle which slightly increased the
      mean diameter. TEM- and SAXS-measured mean diameters when plotted together showed
      similar trend in the variation in the size as the laser power was changed which
      along with extremely similar size distributions for TEM and SAXS validated the
      application of SAXS for size distribution measurement of the synthesized TiO2
      nanoparticles.

PMID- 27709558
TI  - DNA copy number alterations, gene expression changes and disease-free survival in
      patients with colorectal cancer: a 10 year follow-up.
AB  - BACKGROUND: DNA copy number alterations (CNAs) and gene expression changes have
      amply been encountered in colorectal cancers (CRCs), but the extent at which CNAs
      affect gene expression, as well as their relevance for tumor development, are
      still poorly defined. Here we aimed at assessing the clinical relevance of these
      parameters in a 10 year follow-up study. METHODS: Tumors and normal adjacent
      colon mucosa, obtained at primary surgery from 21 CRC patients, were subjected to
      (i) high-resolution array CGH (a-CGH) for the detection of CNAs and (ii)
      microarray-based transcriptome profiling for the detection of gene expression
      (GE) changes. Correlations between these genomic and transcriptomic changes and
      their associations with clinical and histopathological parameters were assessed
      with the aim to identify molecular signatures associated with disease-free
      survival of the CRC patients during a 10 year follow-up. RESULTS: DNA copy number
      gains were frequently detected in chromosomes 7, 8q, 13, 19, 20q and X, whereas
      DNA copy number losses were frequently detected in chromosomes 1p, 4, 8p, 15,
      17p, 18, 19 and 22q. None of these alterations were observed in all samples. In
      addition, we found that 2,498 genes were up- and that 1,094 genes were down
      regulated in the tumor samples compared to their corresponding normal mucosa (p <
      0.01). The expression of 65 genes was found to be significantly associated with
      prognosis (p < 0.01). Specifically, we found that up-regulation of the IL17RA,
      IGF2BP2 and ABCC2 genes, and of genes acting in the mTOR and cytokine receptor
      pathways, were strongly associated with a poor survival. Subsequent integrated
      analyses revealed that increased expression levels of the MMP9, BMP7, UBE2C, I
      CAM, NOTCH3, NOTCH1, PTGES2, HMGB1 and ERBB3 genes were associated with copy
      number gains, whereas decreased expression levels of the MUC1, E2F2, HRAS and
      SIRT3 genes were associated with copy number losses. Pathways related to cell
      cycle progression, eicosanoid metabolism, and TGF-beta and apoptosis signaling,
      were found to be most significantly affected. CONCLUSIONS: Our results suggest
      that CNAs in CRC tumor tissues are associated with concomitant changes in the
      expression of cancer-related genes. In other genes epigenetic mechanism may be at
      work. Up-regulation of the IL17RA, IGF2BP2 and ABCC2 genes, and of genes acting
      in the mTOR and cytokine receptor pathways, appear to be associated with a poor
      survival. These alterations may, in addition to Dukes' staging, be employed as
      new prognostic biomarkers for the prediction of clinical outcome in CRC patients.

PMID- 27709561
TI  - Highly Efficient Catalysis of Azo Dyes Using Recyclable Silver Nanoparticles
      Immobilized on Tannic Acid-Grafted Eggshell Membrane.
AB  - In this study, a facile one-step synthesis of a novel nanocomposite catalytic
      film was developed based on silver nanoparticles (AgNPs) immobilized in tannic
      acid-modified eggshell membrane (Tan-ESM). Tannic acid, as a typical plant
      polyphenol from oak wood, was first grafted onto ESM fibers to serve as both the
      reductant and the stabilizer during the synthesis of AgNPs. The morphology,
      constitution, and thermal stability of the resulting AgNPs@Tan-ESM composites
      were fully characterized to explain the excellent catalytic efficiency of
      AgNPs@Tan-ESM composites. These composite catalysts were applied to the
      degradation of azo dyes which exhibited the high catalytic activity toward Congo
      red and methyl orange according to the kinetic curves. More importantly, they can
      be easily recovered and reused for many times because of their good stability.

PMID- 27709562
TI  - Electrochemical Properties of Rutile TiO2 Nanorod Array in Lithium Hydroxide
      Solution.
AB  - In this paper, rutile TiO2 nanorod arrays are fabricated by a template-free
      method and proposed as a promising anode for aqueous Li-ion battery. The as
      prepared TiO2 nanorod arrays exhibited reversible Li-ion insertion/extraction
      ability in aqueous LiOH electrolyte. Moreover, galvanostatic charge/discharge
      test results demonstrated that the reversible capacity of TiO2 nanorods could
      reach about 39.7 mC cm-2, and 93.8 % of initial capacity was maintained after 600
      cycles at a current density of 1 mA cm-2 (=240 C rate), indicating excellent
      cycling stability and rate capability.

PMID- 27709563
TI  - Potential Suppressive Effects of Two C60 Fullerene Derivatives on Acquired
      Immunity.
AB  - The therapeutic effects of fullerene derivatives on many models of inflammatory
      disease have been demonstrated. The anti-inflammatory mechanisms of these
      nanoparticles remain to be elucidated, though their beneficial roles in allergy
      and autoimmune diseases suggest their suppressive potential in acquired immunity.
      Here, we evaluated the effects of C60 pyrrolidine tris-acid (C60-P) and
      polyhydroxylated fullerene (C60(OH)36) on the acquired immune response in vitro
      and in vivo. In vitro, both C60 derivatives had dose-dependent suppressive
      effects on T cell receptor-mediated activation of T cells and antibody production
      by B cells under anti-CD40/IL-4 stimulation, similar to the actions of the
      antioxidant N-acetylcysteine. In addition, C60-P suppressed ovalbumin-specific
      antibody production and ovalbumin-specific T cell responses in vivo, although T
      cell-independent antibodies responses were not affected by C60-P. Together, our
      data suggest that fullerene derivatives can suppress acquired immune responses
      that require T cells.

PMID- 27709564
TI  - The Potential of Lactobacillus casei and Entercoccus faecium Combination as a
      Preventive Probiotic Against Entamoeba.
AB  - Travellers' diarrhoea caused by enteric protozoa like Entamoeba histolytica is
      among the most common protozoan diseases in developing countries. In developing
      countries, amoebiasis is the second most prevalent protozoan disease. This
      protozoan parasite is often known to coexist as a part of the normal gut
      microbiota. It is estimated that around 50-60 % of population in developing
      countries might be harbouring Entamoeba in an asymptomatic manner. Due to
      physiological perturbation or upon immuno-compromise, it can become virulent and
      then cause diarrhoea, bloody stools and may invade other organs if left
      untreated. Nitroimidazole drugs, namely metronidazole and tinidazole, are widely
      used to treat protozoan infections. These drugs often show dose-dependent side
      effects. With emerging antibiotic resistance, novel therapeutics to prevent
      parasitic infections is required. This study aims to study effect of probiotics
      on prevention of Amoebiasis. In this study, we have investigated the effect of
      selected probiotics on the growth of Entamoeba. From the list of probiotics being
      currently used, five bacterial strains were selected for testing. These probiotic
      strains were co-cultured with Entamoeba, and their effect on Entamoeba
      proliferation was checked. Of the five probiotics chosen, individual treatments
      of Lactobacillus casei and Enterococcus faecium showed a significant reduction of
      up to 71 % in parasite survival only at higher CFUs. When the two probiotics were
      used in combination, the percentage of survival reduced gradually further to 80 %
      at a total CFU of 109 cells/ml of bacteria. The study lays the foundation for
      providing cost-effective prophylactic treatment for amoebiasis without the
      overuse of antibiotics.

PMID- 27709565
TI  - Design and Validation of CRISPR/Cas9 Systems for Targeted Gene Modification in
      Induced Pluripotent Stem Cells.
AB  - The CRISPR/Cas9 system is a powerful tool for precision genome editing. The
      ability to accurately modify genomic DNA in situ with single nucleotide precision
      opens up new possibilities for not only basic research but also biotechnology
      applications and clinical translation. In this chapter, we outline the procedures
      for design, screening, and validation of CRISPR/Cas9 systems for targeted
      modification of coding sequences in the human genome and how to perform genome
      editing in induced pluripotent stem cells with high efficiency and specificity.

PMID- 27709566
TI  - Mutagenesis and Genome Engineering of Epstein-Barr Virus in Cultured Human Cells
      by CRISPR/Cas9.
AB  - The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR
      associated protein 9 nuclease (Cas9) system is a powerful genome-editing tool for
      both chromosomal and extrachromosomal DNA. DNA viruses such as Epstein-Barr virus
      (EBV), which undergoes episomal replication in human cells, can be effectively
      edited by CRISPR/Cas9. We have demonstrated targeted editing of the EBV genome by
      CRISPR/Cas9 in several lines of EBV-infected cells. CRISPR/Cas9-based mutagenesis
      and genome engineering of EBV provides a new method for genetic analysis, which
      has some advantages over bacterial artificial chromosome-based recombineering.
      This approach might also prove useful in the cure of EBV infection. In this
      chapter, we use the knockout of the BART promoter as an example to detail the
      experimental procedures for construction of recombinant EBV in human cells.

PMID- 27709567
TI  - Use of CRISPR/Cas Genome Editing Technology for Targeted Mutagenesis in Rice.
AB  - Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR
      associated protein (Cas) system is a newly emerging mutagenesis (gene-editing)
      tool in genetic engineering. Among the agriculturally important crops, several
      genes have been successfully mutated by the system, and some agronomic important
      traits have been rapidly generated, which indicates the potential applications in
      both scientific research and plant breeding. In this chapter, we describe a
      standard gene-editing procedure to effectively target rice genes and to make
      specific rice mutants using the CRISPR/Cas9 system mediated by Agrobacterium
      transformation.

PMID- 27709568
TI  - All-in-One CRISPR-Cas9/FokI-dCas9 Vector-Mediated Multiplex Genome Engineering in
      Cultured Cells.
AB  - CRISPR-Cas9 enables highly convenient multiplex genome engineering in cultured
      cells, because it utilizes generic Cas9 nuclease and an easily customizable
      single-guide RNA (sgRNA) for site-specific DNA double-strand break induction. We
      previously established a multiplex CRISPR-Cas9 assembly system for constructing
      an all-in-one vector simultaneously expressing multiple sgRNAs and Cas9 nuclease
      or other Cas9 variants including FokI-dCas9, which supersedes the wild-type Cas9
      with regard to high specificity. In this chapter, we describe a streamlined
      protocol to design and construct multiplex CRISPR-Cas9 or FokI-dCas9 vectors, to
      introduce them into cultured cells by lipofection or electroporation, to enrich
      the genomically edited cells with a transient puromycin selection, to validate
      the mutation efficiency by Surveyor nuclease assay, and to perform off-target
      analyses. We show that our protocol enables highly efficient multiplex genome
      engineering even in hard-to-transfect HepG2 cells.

PMID- 27709571
TI  - Generation of Stable Knockout Mammalian Cells by TALEN-Mediated Locus-Specific
      Gene Editing.
AB  - Precise and targeted genome editing using Transcription Activator-Like Effector
      Endonucleases (TALENs) has been widely used and proven to be an extremely
      effective and specific knockout strategy in both cultured cells and animal
      models. The current chapter describes a protocol for the construction and
      generation of TALENs using serial and hierarchical digestion and ligation steps,
      and using the synthesized TALEN pairs to achieve locus-specific targeted gene
      editing in mammalian cell lines using a modified clonal selection strategy in an
      easy and cost-efficient manner.

PMID- 27709569
TI  - CRISPR/Cas9-Mediated Mutagenesis of Human Pluripotent Stem Cells in Defined Xeno
      Free E8 Medium.
AB  - The recent advent of engineered nucleases including the CRISPR/Cas9 system has
      greatly facilitated genome manipulation in human pluripotent stem cells (hPSCs).
      In addition to facilitating hPSC-based disease studies, the application of genome
      engineering in hPSCs has also opened up new avenues for cell replacement therapy.
      To improve consistency and reproducibility of hPSC-based studies, and to meet the
      safety and regulatory requirements for clinical translation, it is necessary to
      use a defined, xeno-free cell culture system. This chapter describes protocols
      for CRISPR/Cas9 genome editing in an inducible Cas9 hPSC-based system, using
      cells cultured in chemically defined, xeno-free E8 Medium on a recombinant human
      vitronectin substrate. We detail procedures for the design and transfection of
      CRISPR guide RNAs, colony selection, and the expansion and validation of clonal
      mutant lines, all within this fully defined culture condition. These methods may
      be applied to a wide range of genome-engineering applications in hPSCs, including
      those that utilize different types of site-specific nucleases such as zinc finger
      nucleases (ZFNs) and TALENs, and form a closer step towards clinical utility of
      these cells.

PMID- 27709570
TI  - Development of CRISPR/Cas9 for Efficient Genome Editing in Toxoplasma gondii.
AB  - Efficient and site-specific alteration of the genome is key to decoding and
      altering the genomic information of an organism. Over the last couple of years,
      the RNA-guided Cas9 nucleases derived from the prokaryotic type 2 CRISPR
      (clustered regularly interspaced short palindromic repeats) systems have
      drastically improved our ability to engineer the genomes of a variety of
      organisms including Toxoplasma gondii. In this chapter, we describe detailed
      protocols for using the CRISPR/Cas9 system adapted from Streptococcus pyogenes to
      perform efficient genetic manipulations in T. gondii such as gene disruption,
      gene tagging and genetic complementation. The technical details of the strategy,
      including CRISPR plasmid construction, target construct generation, parasite
      transfection and positive clone identification are also provided. These methods
      are easy to customize to any gene of interest (GOI) and will greatly accelerate
      studies on this important pathogen.

PMID- 27709572
TI  - Efficient Generation of Gene-Modified Mice by Haploid Embryonic Stem Cell
      Mediated Semi-cloned Technology.
AB  - Haploid embryonic stem cells can be derived from androgenetic embryos produced by
      injection of sperm into enucleated oocytes or by removal of the female pronucleus
      from zygotes. These cells, termed AG-haESCs, can be used in place of sperm to
      produce the so-called semi-cloned (SC) mice. Importantly, AG-haESCs carrying H19
      DMR and IG-DMR knockouts (DKO-AG-haESCs) can efficiently and stably support the
      generation of SC mice via intracytoplasmic AG-haESCs injection (ICAHCI), which
      provides a new route to obtain genetically modified mice. In this chapter, we
      describe the procedures for AG-haESCs culturing, enrichment of haploid cells by
      FACS, genomic manipulation in DKO-AG-haESCs by CRISPR/Cas9 and generation of live
      SC mice with gene-modified DKO-AG-haESCs.

PMID- 27709573
TI  - Insertion of Group II Intron-Based Ribozyme Switches into Homing Endonuclease
      Genes.
AB  - Fungal mitochondrial genomes act as "reservoirs" for homing endonucleases. These
      enzymes with their DNA site-specific cleavage activities are attractive tools for
      genome editing, targeted mutagenesis and gene therapy applications. Herein, we
      present strategies where homing endonuclease open reading frames (HEases ORFs)
      are interrupted with group II intron sequences. The ultimate goal is to achieve
      in vivo expression of HEases that can be regulated by manipulating the splicing
      efficiency of the HEase ORF-embedded group II introns. That addition of exogenous
      magnesium chloride (MgCl2) appears to stimulate splicing of nonnative group II
      introns in Escherichia coli and the addition of cobalt chloride (CoCl2) to the
      growth medium antagonizes the expression of HEase activity (i.e., splicing).
      Group II introns are potentially autocatalytic self-splicing elements and thus
      can be used as molecular switches that allow for temporal regulated HEase
      expression. This should be useful in precision genome engineering, mutagenesis,
      and minimizing off-target activities.

PMID- 27709574
TI  - Generating a Genome Editing Nuclease for Targeted Mutagenesis in Human Cells.
AB  - Gene targeting and editing is an essential tool for both basic research and
      clinical application such as gene therapy. Several endonucleases have been
      invented to fulfill these purposes, including zinc finger nucleases, TALEN, and
      CRISPR/Cas9. Although all of these systems can target DNA sequence with high
      efficiency, they also exert off-target effects and genotoxicity. The off-target
      effects might not hinder their usage in animal models because the correctly
      targeted cells can be selected for further studies. However, the off-target
      effects could cause mutations which may be damaging or cancerous to the patients.
      In this chapter, we describe a genome-editing nuclease method which relies on
      modifying specific amino acids on a monomeric endonuclease, I-SceI, to recognize
      a targeted sequence in the human genome. This nuclease is small in size and shows
      a much lower genotoxicity compared to other nucleases including CRISPR/Cas9.

PMID- 27709575
TI  - Use of Group II Intron Technology for Targeted Mutagenesis in Chlamydia
      trachomatis.
AB  - Dissecting the contribution of genes to virulence in fulfillment of Molecular
      Koch's postulates is essential for developing prevention and treatment strategies
      for bacterial pathogens. This chapter will discuss the application of a targeted,
      intron-based insertional mutagenesis method for creating mutants in the obligate,
      intracellular bacterial pathogen Chlamydia trachomatis. The methods employed for
      intron targeting, mutant selection, and mutant verification will be outlined
      including available selection markers, gene targeting strategies, and potential
      pitfalls.

PMID- 27709577
TI  - In Silico Prediction of Deleteriousness for Nonsynonymous and Splice-Altering
      Single Nucleotide Variants in the Human Genome.
AB  - In silico prediction methods have increasingly been valuable and popular in
      molecular biology, especially in human genetics, for deleteriousness prediction
      to filter and prioritize huge amounts of DNA variation identified by sequencing
      human genomes. There is a rich collection of available methods developed upon
      different levels/aspects of knowledge about how DNA variations affect gene
      expression. Given the fact that their predictions are not always consistent or
      even opposite of what was expected, using consensus prediction or majority vote
      among these methods is preferred to trusting any single one. Because querying
      different databases for different methods is both tedious and time-consuming for
      such big data sets, one database integrating predictions from multiple databases
      can facilitate the process. In this chapter, we describe the general steps of
      obtaining comprehensive predictions and annotations for large numbers of variants
      from dbNSFP, the first and probably the most widely used database of its kind.

PMID- 27709576
TI  - In Silico Approaches to Identify Mutagenesis Targets to Probe and Alter Protein
      Cofactor and Protein-Protein Functional Relationships.
AB  - When performing site-directed mutagenesis experiments to study protein structure
      function relationships, ideally one would know the structure of the protein under
      study. It is also very useful to have structures of multiple related proteins in
      order to determine whether or not particular amino acid residues are conserved in
      the structures either in the active site of an enzyme at the surface of a protein
      or at a putative protein-protein interface. While many protein structures are
      available in the Protein Data Base (PDB), a structure of the protein of interest
      may not be available. In the study of reversible and often transient protein
      protein interactions it is rare to have a structure of the complex of the two
      interacting proteins. In this chapter, methods are described for comparing
      protein structures, generating putative structures of proteins with homology
      models based on the protein primary sequence, and generating docking models to
      predict interaction sites between proteins and cofactor-protein interactions. The
      rationale used to predict mutagenesis targets from these structures and models is
      also described.

PMID- 27709578
TI  - In Silico Methods for Analyzing Mutagenesis Targets.
AB  - Molecular dynamics of complex biological and chemical systems is possible using
      personal computers due to increased computer performance and improved software
      design. Here we describe molecular dynamics methods using Not Another Molecular
      Dynamics (NAMD) and Visual Molecular Dynamics (VMD) programs that aid in
      understanding the structural effects a mutation has on a protein. We describe in
      silico methods for site-specific mutation to standard and phosphorylated amino
      acids. Molecular dynamics equilibrations are used to provide a means for
      measuring structural fluctuations. These fluctuations assist in defining a
      distance coordinate, or reaction coordinate, that is relevant to the function of
      the protein. Adaptive biasing force molecular dynamics are then demonstrated to
      evaluate the energy landscape, or potential of mean force, along the chosen
      reaction coordinate. The potential of mean force identifies variations of the
      predominant structures among mutants that may affect function.

PMID- 27709579
TI  - Methods for Detecting Critical Residues in Proteins.
AB  - In proteins, certain amino acids may play a critical role in determining their
      structure and function. Examples include flexible regions, which allow domain
      motions, and highly conserved residues on functional interfaces, which play a
      role in binding and interaction with other proteins. Detecting these regions
      facilitates the analysis and simulation of protein rigidity and conformational
      changes, and aids in characterizing protein-protein binding. We present a
      protocol that combines graph-theory rigidity analysis and machine-learning-based
      methods for predicting critical residues in proteins. Our approach combines amino
      acid specific information and data obtained by two complementary methods. One
      method, KINARI, performs graph-based analysis to find rigid clusters of amino
      acids in a protein, while the other method relies on evolutionary conservation
      scores to find functional interfaces in proteins. Our machine learning model
      combines both methods, in addition to amino acid type and solvent-accessible
      surface area.

PMID- 27709580
TI  - A Method for Bioinformatic Analysis of Transposon Insertion Sequencing (INSeq)
      Results for Identification of Microbial Fitness Determinants.
AB  - Transposon insertion sequencing is a process whereby microbial fitness
      determinants can be identified on a genome-wide scale. This process uses high
      throughput next generation sequencing to screen for changes in the composition of
      a pool of transposon mutants after exposure to selective conditions. One commonly
      used process for generating transposon insertion sequencing libraries is called
      INSeq that works with mutant pools produced using a modified Mariner transposon.
      Libraries produced using the INSeq process are sequenced on the Illumina
      platform. In this chapter, we describe our method for processing the raw Illumina
      sequencing reads, aligning the reads to a reference sequence to determine read
      counts, and using the online transposon insertion sequencing data analysis
      server, ESSENTIALS, to interpret the results.

PMID- 27709581
TI  - Application of In Vitro Transposon Mutagenesis to Erythromycin Strain Improvement
      in Saccharopolyspora erythraea.
AB  - Transposon mutagenesis is an invaluable technique in molecular biology for the
      creation of random mutations that can be easily identified and mapped. However,
      in the field of microbial strain improvement, transposon mutagenesis has scarcely
      been used; instead, chemical and physical mutagenic methods have been
      traditionally favored. Transposons have the advantage of creating single
      mutations in the genome, making phenotype to genotype assignments less
      challenging than with traditional mutagens which commonly create multiple
      mutations in the genome. The site of a transposon mutation can also be readily
      mapped using DNA sequencing primer sites engineered into the transposon termini.
      In this chapter an in vitro method for transposon mutagenesis of
      Saccharopolyspora erythraea is presented. Since in vivo transposon tools are not
      available for most actinomycetes including S. erythraea, an in vitro method was
      developed. The in vitro method involves a significant investment in time and
      effort to create the mutants, but once the mutants are made and screened, a large
      number of highly relevant mutations of direct interest to erythromycin production
      can be found.

PMID- 27709582
TI  - Engineering Gram-Negative Microbial Cell Factories Using Transposon Vectors.
AB  - The construction of microbial cell factories a la carte largely depends on
      specialized molecular biology and synthetic biology tools needed to reprogram
      bacteria for modifying their existing functions or for bestowing them with new-to
      Nature tasks. In this chapter, we document the use of a series of broad-host
      range mini-Tn5 vectors for the delivery of gene(s) into the chromosome of Gram
      negative bacteria and for the generation of saturated, random mutagenesis
      libraries for studies of gene function. The application of these tailored mini
      transposon vectors, which could also be used for chromosomal engineering of a
      wide variety of Gram-negative microorganisms, is demonstrated in the platform
      environmental bacterium Pseudomonas putida KT2440.

PMID- 27709583
TI  - PERMutation Using Transposase Engineering (PERMUTE): A Simple Approach for
      Constructing Circularly Permuted Protein Libraries.
AB  - Rearrangements that alter the order of a protein's sequence are used in the lab
      to study protein folding, improve activity, and build molecular switches. One of
      the simplest ways to rearrange a protein sequence is through random circular
      permutation, where native protein termini are linked together and new termini are
      created elsewhere through random backbone fission. Transposase mutagenesis has
      emerged as a simple way to generate libraries encoding different circularly
      permuted variants of proteins. With this approach, a synthetic transposon (called
      a permuteposon) is randomly inserted throughout a circularized gene to generate
      vectors that express different permuted variants of a protein. In this chapter,
      we outline the protocol for constructing combinatorial libraries of circularly
      permuted proteins using transposase mutagenesis, and we describe the different
      permuteposons that have been developed to facilitate library construction.

PMID- 27709584
TI  - Transposon Insertion Mutagenesis for Archaeal Gene Discovery.
AB  - Archaea constitute the third domain of life, but studies on their physiology and
      other features have lagged behind bacteria and eukarya, largely due to the
      challenging biology of archaea and concomitant difficulties in methods
      development. The use of genome-wide en masse insertion mutagenesis is one of the
      most efficient means to discover the genes behind various biological functions,
      and such a methodology is described in this chapter for a model archaeon
      Haloferax volcanii. The strategy successfully employs efficient in vitro
      transposition in combination with gene targeting in vivo via homologous
      recombination. The methodology is general and should be transferable to other
      archaeal species.

PMID- 27709585
TI  - Genome-Wide Transposon Mutagenesis in Mycobacterium tuberculosis and
      Mycobacterium smegmatis.
AB  - TnSeq, or transposon (Tn) insertion sequencing, is a powerful method for
      identifying the essential-as well as conditionally essential-regions in a genome,
      both coding and noncoding. The advent of accessible massively parallel DNA
      sequencing technologies in particular has resulted in the increased use of TnSeq
      based approaches to elucidate various aspects of bacterial physiology and
      metabolism. Moreover, the availability of detailed protocols has enabled even
      nonspecialist laboratories to adapt and develop TnSeq approaches to address
      specific research questions. In this chapter, we describe a recently modified
      experimental protocol used in our laboratory for TnSeq in the major human
      pathogen, Mycobacterium tuberculosis, as well as the related non-pathogenic
      mycobacterium, M. smegmatis. The method, which was developed in close
      consultation with pioneers in the field of mycobacterial genetics, includes the
      steps involved in preparing a phage stock, generating a mutant library, selection
      of the library under a specific experimental condition, isolation of genomic DNA
      from the pooled population of mutants, amplification of the sites of Tn insertion
      and, finally, determining the essential genomic regions by next-generation
      sequencing.

PMID- 27709586
TI  - Multiple Site-Directed and Saturation Mutagenesis by the Patch Cloning Method.
AB  - Constructing protein-coding genes with desired mutations is a basic step for
      protein engineering. Herein, we describe a multiple site-directed and saturation
      mutagenesis method, termed MUPAC. This method has been used to introduce multiple
      site-directed mutations in the green fluorescent protein gene and in the moloney
      murine leukemia virus reverse transcriptase gene. Moreover, this method was also
      successfully used to introduce randomized codons at five desired positions in the
      green fluorescent protein gene, and for simple DNA assembly for cloning.

PMID- 27709587
TI  - Seamless Ligation Cloning Extract (SLiCE) Method Using Cell Lysates from
      Laboratory Escherichia coli Strains and its Application to SLiP Site-Directed
      Mutagenesis.
AB  - Cell lysates from laboratory Escherichia coli strains endogenously exhibit
      homologous recombination activity, which can be utilized for seamless DNA cloning
      in vitro. This method, termed Seamless Ligation Cloning Extract (SLiCE) cloning,
      enables high cloning efficiency with simultaneous integration of two unpurified
      DNA fragments into a vector. In addition, the SLiCE method is highly cost
      effective, as several laboratory E. coli strains may be utilized as sources of
      SLiCE. Previously, the SLiCE technique has been applied to site-directed
      mutagenesis to develop a novel technique termed SLiCE-mediated polymerase chain
      reaction (PCR)-based site-directed mutagenesis (SLiP site-directed mutagenesis).
      Two DNA fragments containing a mutation site can be simultaneously integrated
      into a vector while avoiding the introduction of undesirable mutations in the
      vector. Therefore, SLiP site-directed mutagenesis simplifies multiple procedures
      involved in PCR-based site-directed mutagenesis such as overlap extension method
      PCR or the Megaprimer method.

PMID- 27709588
TI  - Facile Site-Directed Mutagenesis of Large Constructs Using Gibson Isothermal DNA
      Assembly.
AB  - Site-directed mutagenesis is a commonly used molecular biology technique to
      manipulate biological sequences, and is especially useful for studying sequence
      determinants of enzyme function or designing proteins with improved activity. We
      describe a strategy using Gibson Isothermal DNA Assembly to perform site-directed
      mutagenesis on large (>~20 kbp) constructs that are outside the effective range
      of standard techniques such as QuikChange II (Agilent Technologies), but more
      reliable than traditional cloning using restriction enzymes and ligation.

PMID- 27709589
TI  - Revised Mechanism and Improved Efficiency of the QuikChange Site-Directed
      Mutagenesis Method.
AB  - Site-directed mutagenesis has been widely used for the substitution, addition or
      deletion of nucleotide residues in a defined DNA sequence. QuikChangeTM site
      directed mutagenesis and its related protocols have been widely used for this
      purpose because of convenience and efficiency. We have recently demonstrated that
      the mechanism of the QuikChangeTM site-directed mutagenesis process is different
      from that being proposed. The new mechanism promotes the use of partially
      overlapping primers and commercial PCR enzymes for efficient PCR and mutagenesis.

PMID- 27709590
TI  - An In Vitro Single-Primer Site-Directed Mutagenesis Method for Use in
      Biotechnology.
AB  - Site-directed mutagenesis is a powerful method to introduce mutation(s) into DNA
      sequences. A number of methods have been developed over the years with a main
      goal being to create a high number of mutant genes. The single-mutagenic primer
      method for site-directed mutagenesis is the most direct method that yields mutant
      genes in about 25-50 % of transformants in a robust, low-cost reaction. The
      supercompetent XL10-Gold bacteria used in the Stratagene protocol carry a phage,
      which may be a problem for some applications; however, in our single-mutagenic
      primer method the supercompetent bacteria are not needed. A thermostable DNA
      polymerase with high fidelity and processivity, such as Phusion DNA polymerase,
      is required for our optimized procedure to avoid extra mutation(s) and enhance
      mutagenic efficiency.

PMID- 27709591
TI  - Use of Megaprimer and Overlapping Extension PCR (OE-PCR) to Mutagenize and
      Enhance Cyclodextrin Glucosyltransferase (CGTase) Function.
AB  - Protein engineering is a very useful tool for probing structure-function
      relationships in proteins. Specifically, site-directed mutagenized proteins can
      provide useful insights into structural, binding and catalytic mechanisms of a
      protein, particularly when coupled with crystallization. In this chapter, we
      describe two protocols for performing site-directed mutagenesis of any protein
      coding sequence, namely, megaprimer PCR and overlapping extension PCR (OE-PCR).
      We use as an example how these two SDM methods enhanced the function of a
      cyclodextrin glucosyltransferase (CGTase) from Bacillus lehensis strain G1.

PMID- 27709592
TI  - Step-By-Step In Vitro Mutagenesis: Lessons From Fucose-Binding Lectin PA-IIL.
AB  - Site-directed mutagenesis is a powerful technique which is used to understand the
      basis of interactions between proteins and their binding partners, as well as to
      modify these interactions. Methods of rational design that are based on detailed
      knowledge of the structure of a protein of interest are often used for
      preliminary investigations of the possible outcomes which can result from the
      practical application of site-directed mutagenesis. Also, random mutagenesis can
      be used in tandem with site-directed mutagenesis for an examination of amino acid
      "hotspots."Lectins are sugar-binding proteins which, among other functions,
      mediate the recognition of host cells by a pathogen and its adhesion to the host
      cell surface. Hence, lectins and their binding properties are studied and
      engineered using site-directed mutagenesis.In this chapter, we describe a site
      directed mutagenesis method used for investigating the sugar binding pattern of
      the PA-IIL lectin from the pathogenic bacterium Pseudomonas aeruginosa. Moreover,
      procedures for the production and purification of PA-IIL mutants are described,
      and several basic methods for characterizing the mutants are discussed.

PMID- 27709593
TI  - Analytical Methods for Assessing the Effects of Site-Directed Mutagenesis on
      Protein-Cofactor and Protein-Protein Functional Relationships.
AB  - To completely understand the role of an amino acid residue that is targeted for
      site-directed mutagenesis a thorough analysis of the impact that the mutation has
      on the function of the protein is required. General methods for performing site
      directed mutagenesis and expressing the recombinant protein variant are
      described. Protein-cofactor interactions are important because cofactors are
      often directly involved in facilitating catalysis by enzymes and in electron
      transfer by redox proteins. Many cofactors also have characteristic spectroscopic
      properties. As such, general methods are described to analyze the spectroscopic,
      redox and catalytic properties of protein-bound cofactors. Methods for assessing
      the effects of a mutation on protein-protein interactions are also described.
      Lastly, methods for assessing the overall structural integrity of the protein are
      described, as this is important to ensure that the mutation has not caused a
      global disruption of protein structure, rather than a specific effect on
      function.

PMID- 27709594
TI  - Biochemical and Biophysical Methods to Examine the Effects of Site-Directed
      Mutagenesis on Enzymatic Activities and Interprotein Interactions.
AB  - Mutations in proteins often affect interactions with partner molecules,
      sequentially changing their activities and functions. In order to examine
      mutagenic effects, we herein describe practical and detailed protocols for
      enzymatic activity assays using ferredoxin (Fd)-NADP+ reductase (FNR) and sulfite
      reductase (SiR), which are electron-transferring enzymes for the Calvin cycle and
      sulfur assimilation in various organisms, respectively. Methods for isothermal
      titration calorimetry and nuclear magnetic resonance spectroscopy, which are very
      useful thermodynamically and mechanically for investigating the effects of
      mutations on intermolecular interactions, are also described with practical
      examples of the Fd-FNR binding system.

PMID- 27709595
TI  - Use of Random and Site-Directed Mutagenesis to Probe Protein Structure-Function
      Relationships: Applied Techniques in the Study of Helicobacter pylori.
AB  - Mutagenesis is a valuable tool to examine the structure-function relationships of
      bacterial proteins. As such, a wide variety of mutagenesis techniques and
      strategies have been developed. This chapter details a selection of random
      mutagenesis methods and site-directed mutagenesis procedures that can be applied
      to an array of bacterial species. Additionally, the direct application of the
      techniques to study the Helicobacter pylori Ferric Uptake Regulator (Fur) protein
      is described. The varied approaches illustrated herein allow the robust
      investigation of the structural-functional relationships within a protein of
      interest.

PMID- 27709596
TI  - Novel Random Mutagenesis Method for Directed Evolution.
AB  - Directed evolution is a powerful strategy for gene mutagenesis, and has been used
      for protein engineering both in scientific research and in the biotechnology
      industry. The routine method for directed evolution was developed by Stemmer in
      1994 (Stemmer, Proc Natl Acad Sci USA 91, 10747-10751, 1994; Stemmer, Nature 370,
      389-391, 1994). Since then, various methods have been introduced, each of which
      has advantages and limitations depending upon the targeted genes and procedure.
      In this chapter, a novel alternative directed evolution method which combines
      mutagenesis PCR with dITP and fragmentation by endonuclease V is described. The
      kanamycin resistance gene is used as a reporter gene to verify the novel method
      for directed evolution. This method for directed evolution has been demonstrated
      to be efficient, reproducible, and easy to manipulate in practice.

PMID- 27709597
TI  - Random Mutagenesis by Error-Prone Polymerase Chain Reaction Using a Heavy Water
      Solvent.
AB  - Heavy water is a form of water that contains a heavier isotope of hydrogen (2H,
      also known as deuterium, D) or oxygen (17O or 18O). When using heavy water as a
      solvent, error-prone polymerase chain reaction (epPCR) can induce random
      mutations independent of the polymerase used or the composition of the PCR
      reaction mixture. This relatively new method can easily be combined with the
      existing epPCR methods to increase the rate of mutations.

PMID- 27709598
TI  - Development and Use of a Novel Random Mutagenesis Method: In Situ Error-Prone PCR
      (is-epPCR).
AB  - Directed evolution methods are increasingly needed to improve gene and protein
      properties. Error-prone PCR is the most efficient method to introduce random
      mutations by reducing the fidelity of the DNA polymerase. However, a highly
      efficient process is required for constructing and screening a diverse
      mutagenesis library since a large pool of transformants is needed to generate a
      desired mutant. We developed a method called in situ error-prone PCR (is-epPCR)
      to improve the efficiency of constructing a mutation library for directed
      evolution. This method offers the following advantages: (1) closed-circular PCR
      products can be directly transformed into competent E. coli cells and easily
      selected by using an alternative antibiotic; (2) a mutant library can be created
      and screened by one-step error-prone amplification of a variable DNA region in an
      expression plasmid; and (3) accumulation of desired mutations in one sequence can
      be obtained by multiple rounds of is-epPCR. Is-epPCR offers a novel, convenient,
      and efficient approach for improving genes and proteins through directed
      evolution.

PMID- 27709599
TI  - Cathepsin K expression in melanoma is associated with metastases.
AB  - INTRODUCTION: Melanoma of the skin shows a tendency to metastasize via lymph or
      blood secreting matrix metalloproteinases and cathepsins, which enable
      penetration through the dermis. Cathepsin K acts in cytoplasm of atypical
      melanocytes and completely cleaves internalized collagen. MATERIALS AND METHODS:
      Expression of cathepsin K was analyzed immunohistochemically in 45 melanomas and
      correlated to morphological and clinical parameters. RESULTS: During six years
      follow up, 13 patients developed lymph node metastases and three of them distant
      metastases. Positive expression of cathepsin K was found in 19 cases. In
      univariate regression analysis histological type, pagetoid spread, mitotic
      activity and cathepsin K expression were significantly connected to metastases.
      Cathepsin K was significantly associated to histologic type, ulceration, pagetoid
      spread and mitotic rate. In multiple logistic regression adjusted to these
      variables, cathepsin K was an independent predictor in occurrence of metastases
      (P=0.015). Median to the occurrence of metastases was 40 months in patients with
      cathepsin K positive expression and 71 months in patients with cathepsin K
      negative expression (P<0.001). CONCLUSIONS: In this preliminary study positive
      expression of cathepsin K in melanoma of the skin is associated with other
      unfavorable prognostic factors. We consider cathepsin K expression in primary
      tumor would significantly precipitate occurrence of metastases.

PMID- 27709601
TI  - Relationship of the number and size of superficial groin lymph nodes with the
      stage of secondary lymphatic edema.
AB  - PURPOSE: This study evaluated the relationships of the size and number of
      superficial groin lymph nodes with the lower limb lymphedema stage and thus
      examined the role of superficial lymphatic lymph nodes in secondary lymphedema
      development. METHODS: We determined the number and size of superficial groin
      lymph nodes using horizontal plane computed tomography (CT) and the lymphedema
      stage in the lower limbs of 25 patients with gynecologic cancer. RESULTS: The
      patients had an average of 2.92 (range, 1-7) superficial groin lymph nodes; the
      mean size of the 146 evaluated lymph nodes was 7.55 mm (range, 5-15 mm). In 19 of
      25 patients (76%), the side with major edema contained fewer superficial groin
      lymph nodes. In total, 22 patients (88%) had fewer superficial groin lymph nodes
      or a smaller total lymph node size on the edematous dominant side. CONCLUSIONS:
      In this evaluation of the link between superficial groin lymph node laterality
      and secondary lymphedema staging, we found that patients with large lymph node
      numbers and sizes tended to present with a relatively earlier stage of
      lymphedema. Our results therefore suggest that the size and number of superficial
      groin lymph nodes affect the lymphedema stage. J. Surg. Oncol. 2016;114:940-946.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27709600
TI  - Cost-Effectiveness and Public Health Effect of Influenza Vaccine Strategies for
      U.S. Elderly Adults.
AB  - OBJECTIVES: To compare the cost-effectiveness of four influenza vaccines
      available in the United States for persons aged 65 and older: trivalent
      inactivated influenza vaccine (IIV3), quadrivalent inactivated influenza vaccine
      (IIV4), a more-expensive high-dose IIV3, and a newly approved adjuvanted IIV3.
      DESIGN: Cost-effectiveness analysis using a Markov model and sensitivity
      analyses. SETTING: A hypothetical influenza vaccination season modeled according
      to possible U.S. influenza vaccination policies. PARTICIPANTS: Hypothetical
      cohort of individuals aged 65 and older in the United States. MEASUREMENTS: Cost
      effectiveness and public health benefits of available influenza vaccination
      strategies in U.S. elderly adults. RESULTS: IIV3 cost $3,690 per quality-adjusted
      life year (QALY) gained, IIV4 cost $20,939 more than IIV3 per QALY gained, and
      high-dose IIV3 cost $31,214 more per QALY than IIV4. The model projected 83,775
      fewer influenza cases and 980 fewer deaths with high-dose IIV3 than with the next
      most-effective vaccine: IIV4. In a probabilistic sensitivity analysis, high-dose
      IIV3 was the favored strategy if willingness to pay is $25,000 or more per QALY
      gained. Adjuvanted IIV3 cost-effectiveness depends on its price and effectiveness
      (neither yet determined in the United States) but could be favored if its
      relative effectiveness is 15% greater than that of IIV3. CONCLUSION: From
      economic and public health standpoints, high-dose IIV3 for adults aged 65 years
      and older is likely to be favored over the other vaccines, based on currently
      available data. The cost-effectiveness of adjuvanted IIV3 should be reviewed
      after its effectiveness has been compared with that of other vaccines and its
      U.S. price is established.

PMID- 27709602
TI  - Responses to Interpersonal Stress: Normative Changes Across Childhood and the
      Impact of Peer Victimization.
AB  - This research examined the development of stress responses across second to sixth
      grades and whether exposure to peer victimization alters stress response
      trajectories. Youth (338 girls; 298 boys; Mage  = 7.97 years, SD = .37) reported
      on stress responses; teachers and youth reported on peer victimization. Latent
      growth curve modeling revealed an increase in effortful engagement responses and
      a decrease in disengagement and involuntary engagement responses during this
      period. Peer victimization disrupted these normative trajectories, resulting in
      less effortful engagement and more effortful disengagement and involuntary stress
      responses in early adolescence. These findings suggest that early peer
      victimization sensitizes youth to stress by interfering with the development of
      effective coping and fostering maladaptive stress responses.

PMID- 27709604
TI  - Annual Research Review: Quality of life and childhood mental and behavioural
      disorders - a critical review of the research.
AB  - BACKGROUND: An individual's subjective perception of well-being is increasingly
      recognized as an essential complement to clinical symptomatology and functional
      impairment in children's mental health. Measurement of quality of life (QoL) has
      the potential to give due weight to the child's perspective. SCOPE AND
      METHODOLOGY: Our aim was to critically review the current evidence on how
      childhood mental disorders affect QoL. First, the major challenges in this
      research field are outlined. Then we present a systematic review of QoL in
      children and adolescents aged 0-18 years formally diagnosed with a mental and
      behavioural disorder, as compared to healthy or typically developing children or
      children with other health conditions. Finally, we discuss limitations of the
      current evidence base and future directions based on the results of the
      systematic review and other relevant literature. FINDINGS AND CONCLUSIONS: The
      systematic review identified 41 eligible studies. All were published after the
      year 2000 and 21 originated in Europe. The majority examined QoL in
      neurodevelopmental disorders, including attention-deficit hyperactivity disorder
      (k = 17), autism spectrum disorder (k = 6), motor disorders (k = 5) and
      intellectual disability (k = 4). Despite substantial heterogeneity, studies
      demonstrate that self-reported global QoL is significantly reduced compared to
      typical/healthy controls across several disorders and QoL dimensions. Parents'
      ratings were on average substantially lower, casting doubt on the validity of
      proxy-report. Studies for large diagnostic groups such as depressive disorders,
      anxiety disorders, (early onset) schizophrenia and eating disorders are largely
      lacking. We conclude that representative, well-characterized normative and
      clinical samples as well as longitudinal and qualitative designs are needed to
      further clarify the construct of QoL, to derive measures of high ecological
      validity, and to examine how QoL fluctuates over time and is attributable to
      specific conditions or contextual factors.

PMID- 27709603
TI  - Does the colonization of new biogeographic regions influence the diversification
      and accumulation of clade richness among the Corvides (Aves: Passeriformes)?
AB  - Regional variation in clade richness can be vast, reflecting differences in the
      dynamics of historical dispersal and diversification among lineages. Although it
      has been proposed that dispersal into new biogeographic regions may facilitate
      diversification, to date there has been limited assessment of the importance of
      this process in the generation, and maintenance, of broad-scale biodiversity
      gradients. To address this issue, we analytically derive biogeographic regions
      for a global radiation of passerine birds (the Corvides, c. 790 species) that are
      highly variable in the geographic and taxonomic distribution of species.
      Subsequently, we determine rates of historical dispersal between regions, the
      dynamics of diversification following regional colonization, and spatial
      variation in the distribution of species that differ in their rates of lineage
      diversification. The results of these analyses reveal spatiotemporal differences
      in the build-up of lineages across regions. The number of regions occupied and
      the rate of transition between regions both predict family richness well,
      indicating that the accumulation of high clade richness is associated with
      repeated expansion into new geographic areas. However, only the largest family
      (the Corvidae) had significantly heightened rates of both speciation and regional
      transition, implying that repeated regional colonization is not a general
      mechanism promoting lineage diversification among the Corvides.

PMID- 27709606
TI  - "We want the world and we want it now": Materialism, time perspectives and
      problem spending tendency of Chinese.
AB  - Chinese consumers' spending has been expanding rapidly in the past decade, and
      along with it household and credit card debt. The present research collected
      evidence to triangulate the contention that materialism is positively related
      with Chinese's problem spending tendency (PST), and that present-time-perspective
      (PTP) and future-time perspectives (FTP) interact systematically with materialism
      to affect PST. A survey of the general population in Macao, China (Study 1; N =
      239) confirmed that materialism was positively correlated with PST. An
      interaction between materialism and PTP intensified the relationship, whereas an
      interaction with FTP weakened the relationship. Another survey with a sample of
      university students (Study 2; N = 223) again found positive relationships among
      PST, materialism, and PTP, as measured by temporal discount rate. But further
      exploration showed that PST was only related with temporal discounting among high
      materialists, but not among low materialists. Study 3 experimentally examined the
      causal effects of materialism and FTP on PST. When being primed of an orientation
      towards materialism (n = 33), the participants' planned consumption doubled that
      of the control group (n = 31). A FTP prime interacted with materialism prime and
      put a "damper" on participants' planned spending (n = 29), compared to their
      counterparts who were not primed of such a time perspective.

PMID- 27709607
TI  - The circular structure of values: The case of China.
AB  - This study examined the circular structure of values in China. The circular
      structure is a central element of Schwartz value theory and visualises the idea
      that some values are similar while others conflict with one another. Whereas
      numerous studies addressed the question whether the circular structure of values
      can be generalised cross-culturally, results for China are inconclusive. In this
      paper, we argue that taking a closer look at China provides a challenge to the
      circular structure and allows for drawing conclusions regarding the limits versus
      generalizability of Schwartz' theory. For this purpose, we first conduct a re
      analysis of Chinese data from a former meta-analysis (Study 1) and second,
      present results from a large study of 10,652 Chinese college students (Study 2).
      Results of Study 1 revealed that graphical representation of the circular
      structure matched theoretical expectations but five out of six samples showed
      relatively bad fit to the theorised structure. By contrast, data in Study 2
      showed a good model fit. As an overall conclusion, the circular structure is well
      supported in the Chinese context, and small sample sizes in previous studies
      might have caused the imperfect match to the prototypical circular structure.

PMID- 27709605
TI  - Fungal pattern receptors down-regulate the inflammatory response by a cross
      inhibitory mechanism independent of interleukin-10 production.
AB  - Cyclic AMP regulatory element binding protein and signal transducer and activator
      of transcription 3 (STAT3) may control inflammation by several mechanisms, one of
      the best characterized is the induction of the expression of the anti
      inflammatory cytokine interleukin-10 (IL-10). STAT3 also down-regulates the
      production of pro-inflammatory cytokines induced by immunoreceptor tyrosine-based
      activation motif (ITAM)-coupled receptors, a mechanism termed cross-inhibition.
      Because signalling via ITAM-dependent mechanisms is a hallmark of fungal pattern
      receptors, STAT3 activation might be involved in the cross-inhibition associated
      with invasive fungal infections. The fungal surrogate zymosan produced the
      phosphorylation of Y705-STAT3 and the expression of Ifnb1 and Socs3, but did not
      induce the interferon (IFN)-signature cytokines Cxcl9 and Cxcl10 in bone marrow
      derived dendritic cells. Unlike lipopolysaccharide (LPS), zymosan induced IL-10
      and phosphorylated Y705-STAT3 to a similar extent in Irf3 and Ifnar1 knockout and
      wild-type mice. Human dendritic cells showed similar results, although the
      induction of IFNB1 was less prominent. These results indicate that LPS and
      zymosan activate STAT3 through different routes. Whereas type I IFN is the main
      effector of LPS effect, the mechanism involved in Y705-STAT3 phosphorylation by
      zymosan is more complex, cannot be associated with type I IFN, IL-6 or
      granulocyte-macrophage colony-stimulating factor, and seems dependent on several
      factors given that it was partially inhibited by the platelet-activating factor
      antagonist WEB2086 and high concentrations of COX inhibitors, p38 mitogen
      activate protein kinase inhibitors, and blockade of tumour necrosis factor-alpha
      function. Altogether, these results indicate that fungal pattern receptors share
      with other ITAM-coupled receptors the capacity to produce cross-inhibition
      through a mechanism involving STAT3 and induction of SOCS3 and IL-10, but that
      cannot be explained through type I IFN signalling.

PMID- 27709608
TI  - Reply from the authors: SSAI guideline on pre-hospital airway management: keep it
      safe and simple.

PMID- 27709609
TI  - How valuable is inpatient electroencephalogram for medical decision-making?
AB  - BACKGROUND: The electroencephalogram (EEG) can support the diagnosis of epilepsy,
      diagnose nonconvulsive status epilepticus and aid in the classification of
      epileptic seizures. Its contribution to the diagnosis of other medical conditions
      or to decision-making in other clinical situations was not established.
      Practically, EEG laboratories frequently encounter EEG referrals that are not
      based on current recommendations. OBJECTIVES: To assess the value of inpatient
      EEG in medical decision-making. METHODS: We retrospectively reviewed the
      inpatient computerized medical information management system and the EEG
      laboratory computerized database for all adult inpatient standard, sleep-deprived
      and bedside EEGs performed during a one-year period. Change in diagnosis and/or
      treatment and the clinical justification for ordering an EEG recording were
      determined. RESULTS: The study group included 584 patients, 313 (54%) men, aged
      55.5 +/- 20.8 years (range 18-95 years). The EEG was clinically justified in 372
      (63.7%) and led to change in diagnosis and/or treatment in 47 (8%) patients.
      These patients were significantly more likely to be admitted to the neurology
      department (P = 0.033), have an admission and discharge diagnosis of seizure or
      epilepsy (P = 0.0001), have a clinically justified EEG (P = 0.0001) and have an
      EEG recording with electrographic seizures (P = 0.0001), interictal epileptiform
      discharges (P = 0.0001) and background abnormalities (P = 0.003). CONCLUSIONS:
      Inpatient EEG can mostly contribute to diagnosis and treatment in patients with a
      seizure or epilepsy. An informed use of the EEG can increase its yield and reduce
      the number of unnecessary referrals, thus shortening waiting time and enabling
      earlier diagnosis and treatment in yet undiagnosed patients.

PMID- 27709610
TI  - Overt and Relational Victimization: A Meta-Analytic Review of Their Overlap and
      Associations With Social-Psychological Adjustment.
AB  - This meta-analytic review includes 135 studies, representing 17 countries, of
      child and adolescent (ages 4-17) samples of overt and relational peer
      victimization and examines the magnitude of overlap between forms of
      victimization and associations with five social-psychological adjustment indices.
      Results indicate a strong intercorrelation between forms of victimization (r- =
      .72). No gender difference with regard to relational victimization was found, but
      boys were slightly higher in overt victimization. Overt victimization is more
      strongly associated with overt aggression; relational victimization is more
      strongly related to internalizing problems, lower levels of received prosocial
      behavior from peers, and relational aggression. Both forms are related to
      externalizing problems. Age and method of assessment were explored as potential
      sources of variability in effect sizes.

PMID- 27709611
TI  - Clinical Development of Cell Therapies: Setting the Stage for Academic Success.
AB  - Cellular therapies have potential to treat a wide range of diseases with
      autologous immunotherapies showing unprecedented therapeutic promise in clinical
      trials. Such therapies are mainly developed by academic researchers applying
      small-scale production, targeting rare and unmet medical needs. Here, we
      highlight the clinical translation of immunotherapy product in an academic
      setting, which may serve as a success model for early academic development of
      cell-based therapeutics.

PMID- 27709612
TI  - Alpha-lipoic acid-stearylamine conjugate-based solid lipid nanoparticles for
      tamoxifen delivery: formulation, optimization, in-vivo pharmacokinetic and
      hepatotoxicity study.
AB  - OBJECTIVES: This study was designed to demonstrate the potential of novel alpha
      lipoic acid-stearylamine (ALA-SA) conjugate-based solid lipid nanoparticles in
      modulating the pharmacokinetics and hepatotoxicity of tamoxifen (TMX). METHODS:
      alpha-lipoic acid-stearylamine bioconjugate was synthesized via carbodiimide
      chemistry and used as a lipid moiety for the generation of TMX-loaded solid lipid
      nanoparticles (TMX-SLNs). TMX-SLNs were prepared by solvent emulsification
      diffusion method and optimized for maximum drug loading using rotatable central
      composite design. The optimized TMX-SLNs were stabilized using 10% w/w trehalose
      as cryoprotectant. In addition, pharmacokinetics and hepatotoxicity of freeze
      dried TMX-SLNs were also evaluated in Sprague Dawley rats. KEY FINDINGS: Initial
      characterization with transmission electron microscopy revealed spherical
      morphology with smooth surface having an average particle size of 261.08 +/- 2.13
      nm. The observed entrapment efficiency was 40.73 +/- 2.83%. In-vitro release
      study showed TMX release was slow and pH dependent. Pharmacokinetic study
      revealed a 1.59-fold increase in relative bioavailability as compared to TMX
      suspension. A decrease in hepatotoxicity of TMX is evidenced by the
      histopathological evaluation of liver tissues. CONCLUSIONS: alpha-lipoic acid
      stearylamine conjugate-based SLNs have a great potential in enhancing the oral
      bioavailability of poorly soluble drugs like TMX. Moreover, this ALA-SA
      nanoparticulate system could be of significant value in long-term anticancer
      therapy with least side effects.

PMID- 27709613
TI  - Quantitative Systems Pharmacology: A Case for Disease Models.
AB  - Quantitative systems pharmacology (QSP) has emerged as an innovative approach in
      model-informed drug discovery and development, supporting program decisions from
      exploratory research through late-stage clinical trials. In this commentary, we
      discuss the unique value of disease-scale "platform" QSP models that are amenable
      to reuse and repurposing to support diverse clinical decisions in ways distinct
      from other pharmacometrics strategies.

PMID- 27709614
TI  - Adolescent adaptation before, during and in the aftermath of the Great Recession
      in the USA.
AB  - This study examines the impact of the "Great Recession" (from December 2007 to
      June 2009) on 8th and 10th graders in the USA, using annual nationally
      representative data from the Monitoring the Future study. Historical changes in
      youth adjustment (self-esteem, depressed mood, risk taking, aggression and
      property crime), school achievement (grade point average [GPA], time spent on
      homework and educational expectations) and structured and unstructured activities
      (volunteering, employment, sports and evenings out for fun) were examined between
      1991 and 2014. Overall, there were only slight changes in mean levels of
      adjustment, achievement and most youth activities. However, the percentage of
      youth working during the school year did decline during the Great Recession.
      Several longer-term trends were also evident, though not directly tied to the
      Great Recession. These include an increase in GPA, a decrease in time spent on
      homework, rising educational expectations and more time spent volunteering.
      Future work should assess how the shift to unpaid work activities (e.g.
      volunteering and internships) among youth is impacting the transition from school
      to work in the contemporary economy, and whether the Great Recession had
      deleterious impacts for younger children or among youth whose parents lost work
      or had their homes foreclosed.

PMID- 27709615
TI  - Organ Chips: Quality Assurance Systems in Regenerative Medicine.
AB  - A class of novel therapies leverages regenerative cell types in disease
      microenvironments. This complex interplay challenges established good
      manufacturing practices, as standards and analytical tools to measure
      regenerative potency are missing. That is, we can build the product right, but we
      do not know if we are building the right product. Here, we suggest that organ
      chips, biomimetic in vitro phenotyping platforms, can serve as key quality
      assurance systems in regenerative medicine.

PMID- 27709616
TI  - Structural similarities and differences in H-NS family proteins revealed by the N
      terminal structure of TurB in Pseudomonas putida KT2440.
AB  - H-NS family proteins play key roles in bacterial nucleoid compaction and global
      transcription. MvaT homologues in Pseudomonas have almost negligible amino acid
      sequence identity with H-NS, but can complement an hns-related phenotype of
      Escherichia coli. Here, we report the crystal structure of the N-terminal
      dimerization/oligomerization domain of TurB, an MvaT homologue in Pseudomonas
      putida KT2440. Our data identify two dimerization sites; the structure of the
      central dimerization site is almost the same as the corresponding region of H-NS,
      whereas the terminal dimerization sites are different. Our results reveal
      similarities and differences in dimerization and oligomerization mechanisms
      between H-NS and TurB.

PMID- 27709617
TI  - Use of accelerometry to investigate physical activity in dogs receiving
      chemotherapy.
AB  - OBJECTIVES: To perform a preliminary study to assess whether single-agent
      palliative or adjuvant chemotherapy has an impact on objectively measured
      physical activity in dogs. METHODS: Fifteen dogs with neoplasia (treatment group)
      wore ActiGraphTM accelerometers for 5-day periods before, during and after
      receiving single-agent adjuvant or palliative chemotherapy. Mean 5-day total
      physical activity and time spent in three different intensities of activity
      (sedentary, light-moderate and vigorous) before, during and after receiving
      chemotherapy were compared to a group of 15 healthy dogs (control group). Results
      were also compared within the treatment group across time. RESULTS: Prior to
      chemotherapy, treated dogs tended to be less active than control dogs. Treatment
      group dogs were slightly more active at restaging than they were prior to
      treatment but had similar activity levels to control dogs. Marked effects of
      chemotherapy on physical activity were not detected. Physical activity was
      slightly lower in treated dogs during chemotherapy when compared to control dogs
      but there was a slight increase in physical activity of treated dogs during
      chemotherapy when compared with pretreatment recordings. There was little change
      in the mean 5-day total physical activity between treated dogs during
      chemotherapy and at restaging but a mild decrease in time spent sedentary and
      increase in time spent in light-moderate activity at this comparison of time
      points. CLINICAL SIGNIFICANCE: Single-agent adjuvant or palliative chemotherapy
      had minimal impact on physical activity levels in dogs with neoplasia.

PMID- 27709618
TI  - The wound healing trajectory and predictors with combined electric stimulation
      and conventional care: one outpatient wound care clinic's experience.
AB  - BACKGROUND: Electric stimulation (E-stim) has been found to be an effective
      treatment in improving wound healing rates. However, the wound healing trajectory
      and its related predictors for complete wound closure (CWC) have not been
      reported with E-stim treatment. MATERIALS AND METHODS: This was a retrospective
      study. Data on 159 patients treated at an outpatient wound clinic utilizing
      combined intervention of E-stim and conventional care were included. The Kaplan
      Meier healing curve together with linear regression models depicted the
      percentage of patients with CWC against time. RESULTS: With 100, 112 and 140 days
      of treatment, the percentages of patients with CWC were 59.12%, 61.01% and
      65.41%, respectively. Linear regression models predicted that all patients would
      achieve CWC by 21.55, 22.26 and 24.80 weeks, respectively. The speed for the
      increase in the number and percentage of patients with CWC peaked between 50-75
      days of treatment. To optimize timely healing, referral to other treatment
      facilities or change of treatment protocol is warranted around the peak time.
      With the combined intervention of E-stim and conventional care, positive
      predictors for CWC included a shorter wound duration at initial evaluation (P =
      0.005, OR = 3.10), better compliance with appointments (P = 0.007, OR = 3.38) and
      the diagnosis of venous leg ulcer (P = 0.001, OR = 3.88). CONCLUSIONS: This study
      provided preliminary data on wound healing trajectory and predictors with
      combined E-stim and conventional care. E-stim seemed to expedite wound healing;
      however, further research studies are needed.

PMID- 27709620
TI  - From population genomics to conservation and management: a workflow for targeted
      analysis of markers identified using genome-wide approaches in Atlantic salmon
      Salmo salar.
AB  - A genotyping assay for the Ion Torrent Ion PGM platform was developed for fast
      and cost-effective targeted genotyping of key single nucleotide polymorphisms
      (SNPs) earlier identified using a genome-wide SNP array in Atlantic salmon Salmo
      salar. The method comprised a simple primer design step for multiplex-polymerase
      chain reaction (PCR), followed by two rounds of Ion Torrent Ion PGM sequencing to
      empirically evaluate marker efficiency in large multiplexes and to optimise or
      exclude them when necessary. Of 282 primer pairs initially tested, 217 were
      successfully amplified, indicating good amplification success (>75%). These
      markers included the sdy partial gene product to determine genetic sex, as well
      as three additional modules comprising SNPs for assessing neutral genetic
      variation (NSNP = 150), examining functional genetic variation associated with
      sea age at maturity (NSNP = 5), and for performing genetic subpopulation
      assignment (NSNP = 61). The assay was primarily developed to monitor long-term
      genetic changes in S. salar from the Teno River, but modules are likely suitable
      for application in a wide range of S. salar populations. Furthermore, the fast
      and versatile assay development pipeline offers a strategy for developing
      targeted sequencing assays in any species.

PMID- 27709619
TI  - The use of disposable skin staples for intestinal resection and anastomosis in 63
      dogs: 2000 to 2014.
AB  - OBJECTIVE: To describe the use of disposable skin staples for intestinal
      resection and anastomosis in dogs and report associated dehiscence and mortality
      rates. METHODS: Retrospective evaluation of medical records of dogs that
      underwent intestinal resection and anastomosis using disposable skin staples
      between 2000 and 2014. Data regarding patient signalment, indication for surgery,
      location of the resection and anastomosis, number of procedures performed,
      evidence of peritonitis at the time of surgery, surgeon qualifications,
      dehiscence, and mortality were obtained from the medical records. Mortality was
      defined as failure to survive beyond 10 days following resection and anastomosis.
      RESULTS: The overall mortality rate of patients undergoing intestinal resection
      and anastomosis was 12.7% (8/63). The most common indication for resection and
      anastomosis was neoplasia (20/63 [31.7%]), followed by foreign body removal
      (19/63 [30.2%]). The overall dehiscence rate was 4.8% (3/63). No difference in
      mortality associated with indication for surgery, whether multiple procedures
      were performed, surgeon qualifications, or evidence of peritonitis at the time of
      surgery was identified. CLINICAL SIGNIFICANCE: In this retrospective study, the
      overall mortality and dehiscence rates using disposable skin staples were similar
      to previously reported outcomes following resection and anastomosis.

PMID- 27709621
TI  - A universal port design for the da Vinci Xi(r) system allowing access to the
      entire colon for colorectal cancer surgery.

PMID- 27709622
TI  - Can we rely on the adequate mesorectum excision and the complete pathological
      response in case of rectal signet-ring cell carcinoma?

PMID- 27709623
TI  - Refractive indices of organo-metallic and -metalloid compounds: A long-range
      corrected DFT study.
AB  - Refractive indices of metal- and metalloid-containing compounds are
      systematically evaluated using the Lorentz-Lorenz equation with polarizabilities
      obtained via density functional theory (DFT). Among exchange-correlation
      functionals studied, the long-range corrected (LC) fuctionals yield the lowest
      errors for the polarizabilities of gaseous compounds and refractive indices of
      liquids. The LC-DFT predicts very well the wavelength dependence of refractive
      indices. A scheme for computing Abbe numbers of organometallic and organometaloid
      compounds is proposed and a refractive index - Abbe number plot for 80 compounds
      is constructed. The compounds containing heavier metals tend to have higher
      refractive index and lower Abbe number, but several outliers, among them Te(CH3
      )2 , Ni(PF3 )4 , Sb(C2 F3 )3 , Hg(C2 F3 )2 , are found. For Hg(C2 F3 )2 , also
      the effect of intramolecular and intermolecular degrees of freedom on
      polarizability is investigated. The absolute relative error in polarizability
      decreases from 5.7% for monomer model to 1.7% when a dimer model (derived from
      the available experimental crystal data) is employed. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27709624
TI  - Adrenaline in anaphylaxis treatment and self-administration: experience from an
      inner city emergency department.
AB  - BACKGROUND: Anaphylaxis is a life-threatening emergency of which reliable
      epidemiological data are lacking. This study aimed to analyze how quickly
      patients presenting with anaphylaxis were treated in emergency and whether
      treatment followed the European Academy of Allergy and Clinical Immunology
      (EAACI) guidelines. METHODS: Patient data were collected between April 2009 and
      April 2013. Emergency doctors completed a questionnaire for adult patients
      presenting at the emergency department (ED) of the St. Pierre hospital in
      Brussels with anaphylaxis. Inclusion criteria were based on the Sampson criteria
      of anaphylaxis. Data were analyzed using a Microsoft Excel database. RESULTS:
      About 0.04% (100/230878) of all emergency visits in adults presented with
      anaphylaxis. 64% of patients received their first medical help later than 30 min
      after symptom onset. 67% of patients received adrenaline, 85% oral
      antihistamines, and 89% received IV glucocorticosteroids. 46/100 patients were
      discharged directly from the ED, of which 87% received further medical
      prescriptions for self-administration: 67% corticosteroids, 83% antihistamines,
      and 9% intramuscular adrenaline. 74% were instructed to consult an allergologist
      for adequate diagnosis. 54/100 patients were hospitalized. CONCLUSION: The
      majority of patients were treated according to the EAACI guidelines for
      management of anaphylaxis, but only a minority received the recommended
      adrenaline auto-injector for self-administration at discharge. Because the
      majority of patients received medical help later than 30 min after symptom onset,
      adrenaline auto-injector prescription is a necessity. The low rate of doctors
      prescribing adrenaline auto-injectors in the ED setting underlines the need to
      train doctors of various backgrounds in prevention and treatment of anaphylaxis
      and the close collaboration with allergologists.

PMID- 27709625
TI  - Structural and component mining of nails using bioengineering techniques.
AB  - The human nail is one of the challenging membranes for the scientists to target
      and to improve the clinical efficacy of ungual formulations. The understanding of
      nail physiology, impact of hydration on its properties and presence of trace
      elements in nails as biomarkers has been explored by various researchers in
      clinical studies. Despite the importance of biophysical techniques for the
      assessment of structure and physiology of nail, minimum literature analyses
      biophysical, biochemical and bioanalytical approaches. However, nowadays
      scientists in bioengineering field are keen in developing non-invasive, reliable
      and reproducible techniques for the assessment of different anatomical and
      functional parameters of nails for testing of ungual products.

PMID- 27709627
TI  - Considering Cognitive Mentalizing Deficits as a Transient and Reversible
      Impairment in Alcohol Dependence: A Response to Fein's Commentary on Maurage et
      al.'s Paper.

PMID- 27709626
TI  - Long-term quality of life after transoral laser microsurgery for laryngeal
      carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Previous studies showed good short-term Quality of
      life (QOL) after Transoral Laser Microsurgery (TLM) for laryngeal cancer. Here,
      we aimed to evaluate QOL after TLM in the long-term. METHODS: Prospective
      longitudinal study. Sixty-two consecutive disease-free patients were evaluated
      using UW-QOL v4 and SF-12 questionnaires, 1 and 5 years after TLM. Changes over
      time were assessed according to age, location, and tumor size. Long-term VHI-10
      was also evaluated. RESULTS: The mean follow-up time was 5.41 +/- 2.02 years. No
      differences in the global UW-QOL score were observed between 1 and 5 years after
      TLM (1135.00 vs. 1127.20; P = 0.4). Activity worsened slightly in the long-term
      (93.03 vs. 87.70; P = 0.02). Forty-two and 58% of the patients reported that
      their health 1 and 5 years after treatment was much better than prior to
      diagnosis. Initially, 3.3% considered their health much worse, which was reduced
      to 1.7% at 5 years. SF-12 scores remained unchanged for both physical and mental
      aspects (P > 0.05). The VHI-10 was 3.81 +/- 5.7 for supraglottic and 7.2 +/- 9.6
      for glottic tumors. CONCLUSION: Patients treated with TLM present a very good
      long-term QOL. Only activity deteriorates over time, while voice and swallowing
      remain satisfactory in the majority of patients. J. Surg. Oncol. 2016;114:789
      795. (c) 2016 2016 Wiley Periodicals, Inc.

PMID- 27709628
TI  - Not your average bigot: The better-than-average effect and defensive responding
      to Implicit Association Test feedback.
AB  - A robust body of literature on the better-than-average effect suggests that
      people believe that they are better than the average others across a variety of
      domains. In two studies, we examined whether these better-than-average beliefs
      occur for bias related to stereotyping and prejudice. Moreover, we investigated
      the hypothesis that better-than-average beliefs will predict defensive responding
      to feedback indicating personal bias (e.g., preferences for majority groups,
      societally endorsed stereotypes). Specifically, we examined defensive responses
      to implicit attitude feedback. Study 1 examined this prediction using archival
      analysis of two large, online samples of participants completing a Weight-related
      Implicit Association Test (IAT). Study 2 conceptually replicated Study 1 using
      nine different, randomly assigned IATs and additional measures of defensiveness.
      In both studies, people generally believed that they were less biased than
      others. Moreover, people responded defensively to feedback indicating they were
      biased. This effect was moderated by better-than-average beliefs such that
      feedback indicating societally consistent bias was related to defensiveness most
      (and sometimes only) when people believed they were better than average
      initially. This work represents the first foray into examining the possible
      moderating role of social-comparative beliefs in predicting responses to implicit
      attitude feedback and spurs several important avenues for future research.

PMID- 27709629
TI  - Development of hepatocellular carcinoma in chronic hepatitis B patients with
      advanced fibrosis is independent of viral genotype.
AB  - Hepatitis B is leading cause of liver related morbidity in Asia with predominant
      genotypes B and C in East-Asia. Data on Serum, intrahepatic viral-markers, and
      long-term follow-up of prevalent genotypes (GT) B and C in patients with biopsy
      proven advanced fibrosis are sparse. To compare serum, intrahepatic viral-markers
      and development of hepatocellular carcinoma (HCC) in GT-B and C in patients with
      advanced fibrosis (Ishak >= 4). Sixty-three treatment-naive patients identified
      with advanced fibrosis on liver-biopsy performed between 1998 and 2000 at
      Singapore General Hospital. FFPE tissue was available for 59 patients and serum
      for 42 patients. HBV-DNA was quantified in serum and liver while qHBsAg
      quantified in serum. Patients were followed-up till December 2015. The median age
      was 47 +/- 16 years, with 77.7% males. About 19 were GT-B, 43 patients were GT-C,
      and 1 had both GT-B and C. Mean follow-up was 13.5 years. The median serum HBV
      DNA was 6.25 +/- 2.17 and 6.58 +/- 1.85 log IU/ml, serum HBsAg was 3.29 +/- 0.80
      and 3.45 +/- 1.85 log IU/ml, and intrahepatic HBV-DNA was 0.52 +/- 3.73
      copies/cell and 0.4 +/- 1.37 copies/cell in the GT-B and C, respectively (P > 0.1
      in all). Complete cirrhosis (Ishak-6) was present in 47.6%, Ishak-5 fibrosis in
      33.3%, and Ishak-4 fibrosis in 19% at recruitment. On follow-up HCC developed in
      8/43 in GT-C and in 3/19 GT-B (P = 0.86). Advanced age and cirrhosis were
      significant factors for development of HCC. No difference in serum HBV-DNA,
      qHBsAg or intrahepatic HBV-DNA was seen in the two genotypes. HCC development
      seen over long-term follow-up was independent of genotypes in patients with
      advanced fibrosis. J. Med. Virol. 89:845-848, 2017. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27709630
TI  - Myeloid-derived suppressor cell-like fibrocytes are increased and associated with
      preserved lung function in chronic obstructive pulmonary disease.
AB  - BACKGROUND: The role of fibrocytes in chronic obstructive pulmonary disease
      (COPD) is unknown. We sought to enumerate blood and tissue fibrocytes in COPD and
      determine the association of blood fibrocytes with clinical features of disease.
      METHODS: Utilizing flow cytometry to identify circulating, collagen type 1+
      cells, we found two populations: (i) CD45+ CD34+ (fibrocytes) and (ii) CD45+ CD34
      [myeloid-derived suppressor cell (MDSC)-like fibrocytes] cells in stable COPD (n
      = 41) and control (n = 29) subjects. Lung resection material from a separate
      group of subjects with (n = 11) or without (n = 11) COPD was collected for tissue
      fibrocyte detection. We examined circulating fibrocyte populations for
      correlations with clinical parameters including quantitative computed tomography
      (qCT) and determined pathways of association between correlated variables using a
      path analysis model. RESULTS: Blood and tissue fibrocytes were not increased
      compared to control subjects nor were blood fibrocytes associated with lung
      function or qCT, but were increased in eosinophilic COPD. Myeloid-derived
      suppressor cell-like fibrocytes were increased in COPD compared to controls [2.3
      (1.1-4.9), P = 0.038]. Our path analysis model showed that collagen type 1
      intensity for MDSC-like fibrocytes was positively associated with lung function
      through associations with air trapping, predominately in the upper lobes.
      CONCLUSION: We have demonstrated that two circulating populations of fibrocyte
      exist in COPD, with distinct clinical associations, but are not prevalent in
      proximal or small airway tissue. Blood MDSC-like fibrocytes, however, are
      increased and associated with preserved lung function through a small airway
      dependent mechanism in COPD.

PMID- 27709631
TI  - Associations between lifestyle factors and hand eczema severity: are tobacco
      smoking, obesity and stress significantly linked to eczema severity?
AB  - BACKGROUND: It has been suggested that lifestyle factors such as smoking,
      overweight and stress may influence the prevalence and severity of hand eczema.
      OBJECTIVES: To investigate the association between lifestyle factors and hand
      eczema severity in a cohort of patients with work-related hand eczema. METHODS:
      Individuals with work-related hand eczema notified in the period between June
      2012 and November 2013 were included in this questionnaire-based cross-sectional
      study. Participants responded to a questionnaire including questions on lifestyle
      factors, as well as a photographic guide for assessment of severity of hand
      eczema and questions on quality of life. RESULTS: A total of 773 individuals (546
      women and 227 men) responded to the questionnaire and were included in the study.
      A strong association was found between tobacco smoking and hand eczema severity
      (p = 0.003), whereas no significant association was found for body weight and
      stress. Other factors linked to severe eczema were male sex and older age (p =
      0.04 and p = 0.01, respectively), and wet work (p = 0.08). CONCLUSION: The data
      from the present study strongly support an association between smoking and hand
      eczema severity. However, owing to the cross-sectional design of the study, no
      conclusion on causation can be drawn.

PMID- 27709632
TI  - Psychological Empowerment Among Urban Youth: Measurement Model and Associations
      with Youth Outcomes.
AB  - Empowerment-based strategies have become widely used method to address health
      inequities and promote social change. Few researchers, however, have tested
      theoretical models of empowerment, including multidimensional, higher-order
      models. We test empirically a multidimensional, higher-order model of
      psychological empowerment (PE), guided by Zimmerman's conceptual framework
      including three components of PE: intrapersonal, interactional, and behavioral.
      We also investigate if PE is associated with positive and negative outcomes among
      youth. The sample included 367 middle school youth aged 11-16 (M = 12.71; SD =
      0.91); 60% female, 32% (n = 117) white youth, 46% (n = 170) African-American
      youth, and 22% (n = 80) identifying as mixed race, Asian-American, Latino, Native
      American, or other ethnic/racial group; schools reported 61-75% free/reduced
      lunch students. Our results indicated that each of the latent factors for the
      three PE components demonstrate a good fit with the data. Our results also
      indicated that these components loaded on to a higher-order PE factor (X2  =
      32.68; df: 22; p = .07; RMSEA: 0.04; 95% CI: .00, .06; CFI: 0.99). We found that
      the second-order PE factor was negatively associated with aggressive behavior and
      positively associated with prosocial engagement. Our results suggest that
      empowerment-focused programs would benefit from incorporating components
      addressing how youth think about themselves in relation to their social contexts
      (intrapersonal), understanding social and material resources needed to achieve
      specific goals (interactional), and actions taken to influence outcomes
      (behavioral). Our results also suggest that integrating the three components and
      promoting PE may help increase likelihood of positive behaviors (e.g., prosocial
      involvement); we did not find an association between PE and aggressive behavior.
      Implications and future directions for empowerment research are discussed.

PMID- 27709633
TI  - What emotional tears convey: Tearful individuals are seen as warmer, but also as
      less competent.
AB  - Earlier research found that the mere sight of tears promotes the willingness to
      provide support to the person shedding the tears. Other research, however, found
      that deliberate responses towards tearful persons could be more negative as well.
      We think this is because tears have ambivalent effects on person perception: We
      predicted that tearful people are seen as warmer, but also as less competent. In
      three studies, we asked participants (total N = 1,042) to form their impression
      of someone based on a picture. The depicted person either displayed visible
      tears, or the tears had been digitally removed. Tearful individuals were
      perceived as being warmer, but also as less competent. In Study 2, we also added
      a measure of perceived sadness. Seeing a tearful face increased perceived
      sadness, and this (partially) explained the reduction in perceived competence of
      the target person. There was no such indirect effect of the tear on perceived
      warmth via perceived sadness. Study 3 found that people would be more likely to
      approach a tearful person to offer help than a tearless individual. At the same
      time, tearful individuals would be more likely to be avoided in situations in
      which the observer needs assistance for an important task.

PMID- 27709634
TI  - Occupational dermatitis in hairdressers - influence of individual and
      environmental factors.
AB  - BACKGROUND: Hairdressers are at risk of developing occupational contact
      dermatitis because of their intense contact with wet work in combination with
      chemicals. OBJECTIVES: To perform an analysis of a cohort study of hairdressers
      with occupational contact dermatitis recognized in the period 2006-2011, focusing
      on individual and environmental factors associated with the disease. METHODS: The
      study was a descriptive, register-based survey including all hairdressers with
      recognized occupational contact dermatitis in Denmark in the period January 2006
      to September 2011. Data were obtained from the Danish National Board of
      Industrial Injuries. RESULTS: The study comprised 381 patients (373 women and 8
      men). The median age was 25 years, 64.8% were apprentices, and 35.2% were fully
      trained hairdressers. The prevalence of atopic dermatitis was 36.0%, and was
      significantly higher among apprentices than among fully trained hairdressers
      (44.9% and 19.4%, respectively) (p < 0.001). Of the patients, 48.3% had their
      dermatitis recognized as occupational irritant contact dermatitis, 46.7% had
      their dermatitis recognized as as occupational allergic contact dermatitis or
      combined allergic and irritant contact dermatitis, and 5.0% were recognized as
      having occupational contact urticaria. CONCLUSION: The low median age, the high
      percentages of atopic dermatitis in apprentices and the fact that more
      apprentices than fully trained hairdressers had recognized occupational contact
      dermatitis underlines the importance of early prevention.

PMID- 27709635
TI  - ISO 17025 validation of a next-generation sequencing assay for relationship
      testing.
AB  - The HID-Ion AmpliSeqTM Identity Panel is a next-generation sequencing assay with
      90 autosomal and 34 Y-chromosome SNPs that are amplified in one PCR step and
      subsequently sequenced using the Ion Personal Genome Machine (Ion PGMTM) System.
      This assay was validated for relationship testing in our ISO 17025 accredited
      laboratory in 2015. Here, the essential parts of the validation report submitted
      to the Danish Accreditation Fund are presented. A total of 100 unrelated Danes
      were typed in duplicates and the locus balance, heterozygote balance (Hb) and
      noise levels were analysed in detail. Two loci were disregarded for casework
      because genotyping was uncertain. Hb for rs7520386 was skewed and high levels of
      noise were observed in rs576261. Three general acceptance criteria for analysis
      of single-source samples were defined: (i) sequencing depth > 200 reads, (ii)
      noise level < 3% and (iii) Hb > 0.3. A Python script named SNPonPGM was developed
      to assist the analyst by highlighting loci that do not fulfil the general
      acceptance criteria. Furthermore, SNPonPGM has functions that reduce the hands-on
      time of the reporting officer to a few minutes per case. Mixtures with DNA from
      two individuals in a 1:24 ratio were readily identified using the three criteria
      and the SNPonPGM script.

PMID- 27709637
TI  - Arabidopsis thaliana serpins AtSRP4 and AtSRP5 negatively regulate stress-induced
      cell death and effector-triggered immunity induced by bacterial effector AvrRpt2.
AB  - Protease inhibitors and their cognate proteases regulate growth, development and
      defense. Serine protease inhibitors (serpins) constitute a large family of genes
      in most metazoans and plants. Drosophila NECROTIC (NEC) gene and its homologues
      in the mammalian system are well-characterized serpins, which play a role in
      regulating proteases that participate in cell death pathways. Although the
      Arabidopsis genome contains several serpin homologs, biological function is not
      known for most of them. Here we show that two Arabidopsis serpins, AtSRP4 and
      AtSRP5, are closest sequence homologue of Drosophila NEC protein, and are
      involved in stress-induced cell death and defense. Expression of both AtSRP4 and
      AtSRP5 genes induced upon ultra-violet (UV)-treatment and inoculation with
      avirulent pathogens. The knockout mutants and amiRNA lines of AtSRP4 and AtSRP5
      exaggerated UV- and hypersensitive response (HR)-induced cell death. Over
      expression of AtSRP4 reduced UV- and HR-induced cell death. Mutants of AtSRP4 and
      AtSRP5 suppressed whereas over-expression of AtSRP4 supported the growth of
      bacterial pathogen Pseudomonas syringae pv. tomato DC3000 carrying the AvrRpt2
      effector, but not other avirulent or virulent pathogens. Results altogether
      identified AtSRP4 and AtSRP5 as negative regulators of stress-induced cell death
      and AvrRpt2-triggered immunity; however, the influence of AtSRP4 was more
      prominent than AtSRP5.

PMID- 27709636
TI  - PTTG1IP and MAML3, novel genomewide association study genes for severity of
      hyperresponsiveness in adult asthma.
AB  - BACKGROUND: The severity of bronchial hyperresponsiveness (BHR) is a fundamental
      feature of asthma. The severity of BHR varies between asthmatics and is
      associated with lack of asthma control. The mechanisms underlying this trait are
      still unclear. This study aimed to identify genes associated with BHR severity,
      using a genomewide association study (GWAS) on the slope of BHR in adult
      asthmatics. METHODS: We performed a GWAS on BHR severity in adult asthmatics from
      the Dutch Asthma GWAS cohort (n = 650), adjusting for smoking and inhaled
      corticosteroid use, and verified results in three other cohorts. Furthermore, we
      performed eQTL and co-expression analyses in lung tissue. RESULTS: In the
      discovery cohort, one genomewide significant hit located in phosphodiesterase 4D,
      cAMP-specif (PDE4D) and 26 SNPs with P-values < 1*10-5 were found. None of our
      findings replicated in adult and childhood replication cohorts jointly. In adult
      cohorts separately, rs1344110 in pituitary tumour-transforming 1 interacting
      protein (PTTG1IP) and rs345983 in Mastermind-like 3 (MAML3) replicated nominally;
      minor alleles of rs345983 and rs1344110 were associated with less severe BHR and
      higher lung tissue gene expression. PTTG1IP showed significant co-expression with
      pituitary tumour-transforming 1, the binding factor of PTTG1lP, and with vimentin
      and E-cadherin1. MAML3 co-expressed significantly with Mastermind-like 2 (MAML2),
      both involved in Notch signalling. CONCLUSIONS: PTTG1IP and MAML3 are associated
      with BHR severity in adult asthma. The relevance of these genes is supported by
      the eQTL analyses and co-expression of PTTG1lP with vimentin and E-cadherin1, and
      MAML3 with MAML2.

PMID- 27709638
TI  - IgE-associated allergic disorders: recent advances in etiology, diagnosis, and
      treatment.
AB  - IgE-associated allergic diseases belong to the most common inflammatory
      conditions. Their clinical manifestation ranges from mild symptoms to life
      threatening episodes. Often patients experience a reduction in physical and
      psychologic well-being and suffer from a decreased quality of life due to disease
      activity. The continuously rising number of people that are affected by an
      allergic condition indicates an urgent need for better diagnostics and more
      efficient treatment options. Recent progress in the understanding of
      pathophysiologic mechanisms underlying IgE-associated allergic disorders has led
      to the identification of novel therapeutic targets and the development of drug
      candidates that are currently under evaluation. In this review, we highlight
      studies and clinical trials, which have helped to gain further insight in the
      etiology of IgE-associated allergic conditions as well as advances in the
      development of diagnostic tools and therapeutic approaches recently published in
      Allergy (European Journal of Allergy and Clinical Immunology).

PMID- 27709639
TI  - Fast and accurate determination of the relative binding affinities of small
      compounds to HIV-1 protease using non-equilibrium work.
AB  - The fast pulling ligand (FPL) out of binding cavity using non-equilibrium
      molecular dynamics (MD) simulations was demonstrated to be a rapid, accurate and
      low CPU demand method for the determination of the relative binding affinities of
      a large number of HIV-1 protease (PR) inhibitors. In this approach, the ligand is
      pulled out of the binding cavity of the protein using external harmonic forces,
      and the work of pulling force corresponds to the relative binding affinity of HIV
      1 PR inhibitor. The correlation coefficient between the pulling work and the
      experimental binding free energy of R=-0.95 shows that FPL results are in good
      agreement with experiment. It is thus easier to rank the binding affinities of
      HIV-1 PR inhibitors, that have similar binding affinities because the mean error
      bar of pulling work amounts to deltaW=7%. The nature of binding is discovered
      using the FPL approach. (c) 2016 Wiley Periodicals, Inc.

PMID- 27709640
TI  - Distinguishing and quantifying the torquoselectivity in competitive ring-opening
      reactions using the stress tensor and QTAIM.
AB  - Currently the theories to explain and predict the classification of the
      electronic reorganization due to the torquoselectivity of a ring-opening reaction
      cannot accommodate the directional character of the reaction pathway; the
      torquoselectivity is a type of stereoselectivity and therefore is dependent on
      the pathway. Therefore, in this investigation we introduced new measures from
      quantum theory of atoms in molecules and the stress tensor to clearly distinguish
      and quantify the transition states of the inward (TSIC) and outward (TSOC)
      conrotations of competitive ring-opening reactions of 3-(trifluoromethyl)cyclobut
      1-ene and 1-cyano-1-methylcyclobutene. We find the metallicity xi(rb ) of the
      ring-opening bond does not occur exactly at the transition state in agreement
      with transition state theory. The vector-based stress tensor response betasigma
      was used to distinguish the effect of the CN, CH3 , and CF3 groups on the TSIC
      and TSOC paths that was consistent with the ellipticity epsilon, the total local
      energy density H(rb ) and the stress tensor stiffness Ssigma . We determine the
      directional properties of the TSIC and TSOC ring-opening reactions by
      constructing a stress tensor UsigmaTS space with trajectories TsigmaTS (s) with
      length l in real space, longer l correlated with the lowest density functional
      theory-evaluated total energy barrier and hence will be more thermodynamically
      favored. (c) 2016 Wiley Periodicals, Inc.

PMID- 27709641
TI  - Chemotherapy dosing in achondroplastic dwarfism: a case report and review of
      literature.
AB  - WHAT IS KNOWN AND OBJECTIVE: CASE DESCRIPTION: A 74-year-old female with
      achondroplastic dwarfism was diagnosed with ER-, BR- and HER2- breast cancer. No
      guideline currently exists to direct chemotherapy dosing in this population. She
      received neoadjuvant chemotherapy based on body surface area utilizing actual
      height and weight with dose-dense doxorubicin and cyclophosphamide followed by
      paclitaxel with the use of granulocyte colony-stimulating factor. Satisfactory
      clinical response and remission were achieved, and treatment proceeded without
      any significant toxicity or delays. WHAT IS NEW AND CONCLUSION: In the absence of
      guideline recommendations, dosing chemotherapy based on actual height and weight
      in patients with achondroplastic dwarfism may be safe and appropriate.

PMID- 27709642
TI  - Nonischaemic priapism associated with selective serotonin-3 receptor antagonist.
AB  - Priapism is a rare but severe urological emergency of erection of penis in the
      absence of physical and psychological sexual stimulation. Priapism is often
      idiopathic and is commonly associated with medications and underlying medical or
      traumatic causes. In this report, we present a case of a 70-year-old White
      Caucasian man who developed priapism after the administration of ondansetron,
      which is a selective serotonin type-3 (5-HT3) receptor antagonist. This case is
      unique, because, to date, there are only two presented cases in literature. The
      objective of this case report is to highlight the importance of recognising the
      possibility of priapism with ondansetron because this condition is not commonly
      seen in clinical practice to be associated with ondansetron and may go
      unrecognised. Also, potential pathophysiological mechanisms involved in the
      development of ondansetron-induced priapism are presented.

PMID- 27709643
TI  - Freezability of water buffalo bull (Bubalus bubalis) spermatozoa is improved with
      the addition of curcumin (diferuoyl methane) in semen extender.
AB  - Effects of curcumin as antioxidant in extender were evaluated on freezability of
      buffalo spermatozoa. Semen from each of the five bulls (n = 3 replicates, six
      ejaculates/bull, a total of 30 ejaculates) was diluted in Tris-citric acid
      extender containing curcumin (0.5, 1.0, 1.5 or 2.0 mM) or control. At pre
      freezing and post-thawing, total antioxidant contents (MUM/L) and lipid
      peroxidation levels (MUM/ml) were higher (p < .05) and lower (p < .05)
      respectively, with 1.5 and 2.0 mM compared to 0.5 and 1.0 mM curcumin and
      control. At post-thawing, progressive motility (PM, %) and rapid velocity (RV, %)
      were higher (p < .05) with 1.5 mM compared to other doses of curcumin and control
      (except in case of RV, 1.5 was similar with 1.0 mM). Kinematics (average path
      velocity, MUm/s; straight-line velocity, MUm/s; curved-line velocity, MUm/s;
      straightness, %; linearity, %), in vitro longevity (%, PM and RV) and DNA
      integrity (%) at post-thawing were higher (p < .05) with 1.5 mM compared to
      control. At post-thawing, supravital plasma membrane integrity (%) and viable
      spermatozoa with intact acrosome (%) were higher with 1.5 compared to 2.0 mM
      curcumin and control. We concluded that freezability of water buffalo spermatozoa
      is improved with the addition of 1.5 mM curcumin in extender.

PMID- 27709644
TI  - A case of hypopituitarism accompanying Kearns-Sayre syndrome treated with human
      chorionic gonadotropin: A case report and literature review.
AB  - Kearns-Sayre syndrome (KSS) is a disorder caused by mutations in mitochondrial
      DNA. Here, we report an unusual case of Kearns-Sayre syndrome accompanied by
      hypopituitarism (deficiencies in reproductive and growth hormones). A 20-year-old
      male presented with growth retardation for the last 8 years, as well as the
      following findings: short stature, delayed puberty, myasthenia, an extraocular
      movement deficit, drooping eyelids, pectus carinatum and scoliosis. Cerebral
      enhanced magnetic resonance imaging revealed dysplasias of the pituitary, white
      matter and cerebellum. Laboratory work-up showed subnormal testosterone and
      growth hormone levels, a subnormal testicular volume, sensorineural deafness,
      pigmentary retinopathy, complete right bundle branch block and left anterior
      bundle branch block. Pathological examination revealed ragged red muscle fibres.
      Thus, this rare case involved the coexistence of Kearns-Sayre syndrome and
      hypopituitarism in a patient. Administration of coenzyme Q10 for the KSS and
      hormone replacement therapy for the endocrinopathies were performed for treatment
      of this patient.

PMID- 27709646
TI  - Multiple program/multiple data molecular dynamics method with multiple time step
      integrator for large biological systems.
AB  - Parallelization of molecular dynamics (MD) simulation is essential for
      investigating conformational dynamics of large biological systems, such as
      ribosomes, viruses, and multiple proteins in cellular environments. To improve
      efficiency in the parallel computation, we have to reduce the amount of data
      transfer between processors by introducing domain decomposition schemes. Also, it
      is important to optimize the computational balance between real-space non-bonded
      interactions and reciprocal-space interactions for long-range electrostatic
      interactions. Here, we introduce a novel parallelization scheme for large-scale
      MD simulations on massively parallel supercomputers consisting of only CPUs. We
      make use of a multiple program/multiple data (MPMD) approach for separating the
      real-space and reciprocal-space computations on different processors. We also
      utilize the r-RESPA multiple time step integrator on the framework of the MPMD
      approach in an efficient way: when the reciprocal-space computations are skipped
      in r-RESPA, processors assigned for them are utilized for half of the real-space
      computations. The new scheme allows us to use twice as many as processors that
      are available in the conventional single program approach. The best performances
      of all-atom MD simulations for 1 million (STMV), 8.5 million (8_STMV), and 28.8
      million (27_STMV) atom systems on K computer are 65, 36, and 24 ns/day,
      respectively. The MPMD scheme can accelerate 23.4, 10.2, and 9.2 ns/day from the
      maximum performance of single-program approach for STMV, 8_STMV, and 27_STMV
      systems, respectively, which correspond to 57%, 39%, and 60% speed up. This
      suggests significant speedups by increasing the number of processors without
      losing parallel computational efficiency. (c) 2016 Wiley Periodicals, Inc.

PMID- 27709645
TI  - Selective plasma exchange can reduce auto-antibodies in patients with bullous
      pemphigoid without affecting factor XIII and fibrinogen.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering skin disorder characterized
      by circulating serum IgG antibodies against two hemidesmosomal proteins: BP180
      and BP230. Fundamentally, immunosuppressive therapies are administered to treat
      this disease, but plasmapheresis can be added for refractory patients. We
      experienced the case of a 63-year-old patient with refractory BP for which we
      administered double filtration plasmapheresis (DFPP). His skin lesions improved
      along with decreased IgG BP180 antibodies, but factor XIII (FXIII) and fibrinogen
      were also reduced by DFPP repetition. Reportedly, deficiency of those factors can
      cause lethal bleeding. Especially, decreased FXIII cannot be detected by
      prolongation of bleeding or coagulation time. To prevent further reduction of
      those factors and bleeding complications, DFPP was switched to selective plasma
      exchange (SePE), a new modality of plasmapheresis that uses a membrane plasma
      separator with smaller than ordinary pores. SePE further reduced pathogenic IgG
      BP180 antibodies, but FXIII and fibrinogen recovered. For this case, we measured
      the mean of reduction ratios in serum IgG and FXIII both before and after
      plasmapheresis sessions and detected the decreased levels of FXIII and fibrinogen
      during DFPP. We were able to switch to SePE from DFPP appropriately before any
      bleeding event occurred. The utility of SePE was demonstrated, especially for the
      reduction of pathogenic antibodies with retention of FXIII and fibrinogen, which
      have the longest half-lives among coagulation factors and which take a long time
      to recover.

PMID- 27709647
TI  - Multi-drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex
      infection outbreak in dogs and cats in a veterinary hospital.
AB  - BACKGROUND: Members of the Acinetobacter calcoaceticus-Acinetobacter baumannii
      complex cause severe outbreaks in humans, and are increasingly reported in
      animals. OBJECTIVE AND METHODS: A retrospective study, describing a severe
      outbreak in dogs and cats caused by a multidrug resistant member of the
      Acinetobacter calcoaceticus-Acinetobacter baumannii complex in a veterinary
      hospital, between July 2010 and November 2012. RESULTS: The study included 19
      dogs and 4 cats. Acinetobacter calcoaceticus-Acinetobacter baumannii complex
      bacteria were isolated from urine (9 animals), respiratory tract (11), tissues
      (3) and blood (1). The most common infection-associated findings included fever,
      purulent discharge from endotracheal tubes, hypotension, and neutropaenia.
      Infections led to pneumonia, urinary tract infection, cellulitis and sepsis.
      Infection was transmitted in the intensive care unit, where 22 of 23 animals were
      initially hospitalised. The mortality rate was 70% (16 of 23 animals), and was
      higher in cases of respiratory infection compared to other infections. Aggressive
      environmental cleaning and disinfection, with staff education for personal
      hygiene and antisepsis, sharply decreased the infection incidence. CLINICAL
      SIGNIFICANCE: Health care-associated outbreaks with multidrug resistant
      Acinetobacter calcoaceticus-Acinetobacter baumannii complex in dogs and cats are
      potentially highly fatal and difficult to eradicate, warranting monitoring,
      antiseptic techniques and judicious antibiotic use.

PMID- 27709648
TI  - Headless spermatozoa in infertile men.
AB  - Spermatozoa morphology, an important parameter in a semen specimen's potential
      fertility evaluation, is a significant factor for in vitro fertilisation in
      assisted reproductive technology. Eleven sterile men with headless spermatozoa, a
      type of human teratozoospermia, are presented. Their ejaculates' headless
      spermatozoa percentages were high with rare normal spermatozoa forms.
      Additionally, abnormal morphology (e.g. round-headed or microcephalic
      spermatozoa) was also found. Spermatozoa motility was somewhat affected,
      potentially because of the missing mitochondrial sheath at the sperm tail base.
      Patients who underwent assisted reproductive technology treatment experienced
      adverse pregnancy outcomes. Work types and corresponding environments seemed
      irrelevant, but specific family history may have prompted its genetic origin.
      Computer-assisted semen analysis systems easily mistake headless spermatozoa as
      oligozoospermia because of nonrecognition of the loose head. However,
      morphological testing, especially with an electronic microscope, clearly
      identifies abnormal spermatozoa. Future exploration requires more methods
      investigating the frequency and percentage of this morphological abnormality in
      different populations with varied fertility levels. Such research would estimate
      the probable correlation of the abnormality with other semen parameters and
      examine the potential developmental or genetic origins. During clinical work,
      medical staff should detect these cases, avoid misdiagnosis and provide proper
      consultation about diagnosis and assisted reproductive technology treatment.

PMID- 27709649
TI  - Histological alterations in Leydig cells and macrophages in azoospermic men.
AB  - The study aimed to compare the histological features of Leydig cells and
      macrophages in the testicular interstitium of obstructive versus nonobstructive
      azoospermia. Thirty-nine azoospermic men undergoing testicular sperm extraction
      during intracytoplasmic sperm injection were allocated into obstructive
      azoospermia group (GI) and nonobstructive azoospermia group (GII) which was
      subdivided into Sertoli cell-only syndrome (GIIA), germ cell arrest (GIIB) and
      hypospermatogenesis (GIIC) subgroups. Serum LH, FSH and testosterone levels were
      measured. Ultrastructural changes and the mean number of CD68-positive cells were
      estimated in the different groups. In GIIA, Leydig cells' processes came in
      contact with macrophages and showed smooth endoplasmic reticulum dilatation. In
      GIIB, Leydig cells showed apoptotic changes. Macrophages were commonly
      encountered in their vicinity demonstrating large number of lysosomes. In GIIC,
      Leydig cells showed euchromatic nuclei. Macrophages showed expulsion of their
      lysosomal contents in the interstitium surrounded by apoptotic bodies. The mean
      count of total CD68-positive macrophages was higher in cases of obstructive
      azoospermia with nonsignificant differences compared to nonobstructive
      azoospermia groups. Significant increase in FSH level was detected in GIIA
      compared to GI. It is concluded that structural interactions might take place
      between Leydig cells and macrophages in the interstitial tissue of azoospermic
      men.

PMID- 27709650
TI  - Inflammatory and anti-inflammatory cytokines in the seminal plasma of infertile
      men suffering from varicocele.
AB  - Varicocele is one of causes of the declined sperm quality and low sperm
      production, which can lead to infertility in males. There are several
      experimental and epidemiological findings which support the idea that
      inflammatory mechanisms play an essential role in varicocele pathogenesis.
      Besides, in this pathological state, interleukin-37 (IL-37) as an anti
      inflammatory cytokine is able to bind interleukin-18-binding protein (IL-18BP),
      and subsequently binds IL-18 receptor beta, inhibiting the pro-inflammatory
      activity of IL-18. To explore the interaction between IL-37 and IL-18 in
      infertility, we measured the amount of these cytokines in the seminal fluid of
      infertile men affected by varicocele. The seminal plasma levels of IL-37 and IL
      18 were measured in 75 infertile men with varicocele and 75 healthy fertile
      controls (age range, 30-48 years) using enzyme-linked immunosorbent assay. The
      seminal levels of IL-37 and IL-18 were significantly increased in infertile men
      with varicocele when compared to fertile controls (p < .0001). Because of the
      essential role(s) of cytokines in inflammatory response of cell systems, it could
      be possible that sperm motility is reduced following increased IL-18, activated
      neutrophils and reactive oxygen species in semen of infertile patients with
      varicocele. Moreover, the results of this study indicated that interaction
      between IL-37 and IL-18Rbeta can lead to reduced inflammatory responses. It seems
      that IL-37 might be a potential biomarker and therapeutic target for male
      infertility.

PMID- 27709651
TI  - Epididymal leiomyoma: a benign intrascrotal tumour.
AB  - Physicians will be rarely confronted with epididymal tumours. These represent
      only 5% of intrascrotal tumours and are mostly (75%) benign. We report the case
      of a 50-year-old white male who was presented with a 5-year history of a slow
      growing, left scrotal mass, noted through self-examination. Ultrasound study of
      the scrotum identified a well-circumscribed paratesticular mass. On inguinal
      surgical exploration, a solid, encapsulated, grey-white mass at the tail of the
      left epididymis was identified and excised, with intra-operative pathological
      consultation showing no signs of malignancy. The diagnosis of an epididymal
      leiomyoma was determined through subsequent immune-histopathological analysis.
      Diagnostic steps preceding operative exploration of a paratesticular, epididymal
      tumour are briefly analysed and physicians are encouraged to avoid a radical
      approach, without prior pathological consultation. Epididymal leiomyomas are
      benign tumours that can be cured through simple, organ-preserving surgical
      excision.

PMID- 27709652
TI  - Circulating Epstein-Barr virus-encoded micro-RNAs as potential biomarkers for
      nasal natural killer/T-cell lymphoma.
AB  - Nasal natural killer/T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)
      associated malignancy and is characterized by local invasion and widespread
      dissemination, with a consequent poor prognosis. Micro-RNAs (miRNAs) play roles
      in the pathogenesis of several malignancies by regulating gene expression and
      have been recently identified as stable entities in serum. Here, we investigated
      the value of circulating EBV-miRNAs as biomarkers for NNKTL. Sera of patients
      with NNKTL were subjected to miRNA polymerase chain reaction (PCR)-array
      analysis, after which serum EBV-miRNA levels were verified using quantitative
      PCR. The latter analysis revealed high miR-BART2-5p, miR-BART7-3p, miR-BART13-3p,
      and miR-BART1-5p expression levels in sera of patients with NNKTL and indicated
      accurate values for discriminating patients with NNKTL from healthy controls.
      Levels of these 4 EBV-miRNAs, which were secreted from NNKTL cells, significantly
      decreased after treatment compared with those before treatment. Furthermore, a
      high circulating miR-BART2-5p level was associated with disease progression and
      poor prognosis in patients with NNKTL. Our findings demonstrate that circulating
      EBV-miRNAs, particularly miR-BART2-5p, may serve as potential diagnostic and
      prognostic biomarkers in patients with NNKTL.

PMID- 27709653
TI  - Use of the ages and stages questionnaire adapted for South Africa and Zambia.
AB  - BACKGROUND: There are few readily available, relatively easy to use and
      culturally adaptable developmental assessment tools for young children in
      southern Africa. The overarching aim of this study is to test the psychometric
      properties, contextual appropriateness and cut-off scores across 21 age groups of
      the Ages and Stages Questionnaire Third Edition (Squires & Bricker, ) among a
      group of typically developing children in South Africa and Zambia through a
      combination of both caregiver-report and direct observations, and to compare
      children's performance across sociodemographic variables. METHODS: The sample
      consisted of 853 children (50.5% Zambia, with 50.1% girls for Zambia and 50%
      girls for South Africa) aged 2 months to 60 months. Information on caregiver
      employment, education and household assets were also obtained. RESULTS: The
      psychometric properties of the ASQ-3 in southern Africa are consistent with those
      found in the extant literature. Analysis of item difficulty at each age reveals
      adequate levels of difficulty for majority of the items, with exception of the
      problem solving domain where half of the items at 54 and 60 months have poor pass
      rates. Sociodemographic variables were significantly associated with children's
      performance: higher caregiver levels of education are associated with higher
      toddler scores on the personal-social domain and higher preschooler scores on the
      problem solving domain; children whose caregivers earn a salary have higher fine
      motor scores during toddlerhood and higher problem solving scores during
      preschool and children who attend preschools have higher gross motor scores
      during toddlerhood and higher fine motor scores during the preschool years.
      CONCLUSIONS: Findings provide evidence to support the psychometric properties and
      feasibility of using the ASQ-3 in both South Africa and Zambia through a
      combination of caregiver-report and direct observations.

PMID- 27709654
TI  - Coconut oil induced production of a surfactant-compatible lipase from Aspergillus
      tamarii under submerged fermentation.
AB  - Filamentous fungi are efficient producers of lipases. The present study focuses
      on identification of a potent lipolytic fungus and enhancement of lipase
      production through optimization of nutritional and cultural conditions under
      submerged fermentation. Molecular characterization of the fungus by 18S rDNA
      sequencing revealed its identity as Aspergillus tamarii with 98% homology.
      Maximum lipase production was noted in mineral salts medium supplemented with
      coconut oil (2.5%, v/v). A combination of ammonium chloride (2%, w/v) and
      tryptone (2%, w/v) facilitated maximum lipase production at pH 5 of the
      production medium. A carbon: nitrogen ratio of 1:4 led to significant (p <
      0.00008) increase in the enzyme production in the presence of surfactant
      cetyltrimethylammonium bromide (0.5%, w/v). Maximum lipase activity (2,32,500 +/-
      192 U/ml/min) was recorded after 7 days of incubation at 25  degrees C on a
      rotary shaker at 120 rpm. A 9.8-fold increase in lipase activity was recorded
      after optimization of the process parameters. Addition of crude lipase enhanced
      the oil stain removal activity of a commercially available detergent by 2.2-fold.
      The current findings suggest the potentiality of this fungal lipase to be used in
      detergent formulation.

PMID- 27709655
TI  - Elevated serum homocysteine level as an independent risk factor for erectile
      dysfunction: a prospective pilot case-control study.
AB  - Homocysteine is an amino acid that is produced from the metabolic demethylation
      of dietary methionine. It has gained arising attention for its association with
      increased risk of myocardial infarction, stroke and venous thromboembolism.
      Erectile dysfunction (ED), especially for vasculogenic ED, is a vascular disorder
      of cavernosal vascular bed. In this prospective pilot case-control study, we
      investigated plasma homocysteine levels in 32 ED patients and 20 healthy control
      men. Related patients characteristics including age, weight, height, marital
      status, smoking and drinking status, level of education were collected and
      analysed as well as penile colour Doppler ultrasound parameters. ED patients were
      further categorised into mild, moderate and severe ED based on 5-item of the
      International Index of Erectile Function. Higher homocysteine levels were
      observed in ED patients as compared with controls (p < .05). A multivariate
      logistic regression with likelihood ratio test revealed that homocysteine and
      penile peak systolic blood flow velocity (PSV) levels posed significant
      indicators for ED (chi-square of likelihood ratio = 20.42, df = 2, p < .005) as
      well as moderate and severe ED occurrence (chi-square of likelihood ratio =
      28.50, df = 2, p < .005). The threshold value of homocysteine concentration to
      discriminate ED and control subjects was 12.65 MUmol/L by performing receiver
      operating characteristic curve analyses. These data suggested that elevation of
      homocysteine levels was associated with an increased risk of ED.

PMID- 27709656
TI  - Predicting clinical relevance of grapefruit-drug interactions: a complicated
      process.
AB  - WHAT IS KNOWN AND OBJECTIVE: Grapefruit juice interacts with a number of drugs.
      This commentary provides feedback on a previously proposed approach for
      predicting clinically relevant interactions with grapefruit juice based on the
      average inherent oral bioavailability (F) and magnitude of increase in
      bioavailability with other CYP3A inhibitors of the drug. COMMENT: Additional
      factors such as variability of the magnitude of the pharmacokinetic interaction
      among individuals, product monograph cautionary statements and vulnerability of
      the patient population should be considered. WHAT IS NEW AND CONCLUSION: A flow
      diagram is provided that should improve prediction of the pharmacokinetic
      interaction and clinical relevance for affected drugs and that recommends
      different courses of action for patient management. Forecasting the clinical
      importance of a particular drug interaction with grapefruit can be improved
      through consideration of additional readily available drug regulatory
      information.

PMID- 27709657
TI  - Pyoderma gangrenosum of the scalp: pathergic response to herpes zoster infection.

PMID- 27709658
TI  - Comment on: pharmacy-led medication reconciliation programmes at hospital
      transitions: a systematic review and meta-analysis.

PMID- 27709659
TI  - Human immunodeficiency virus associated thrombotic thrombocytopenic purpura, a
      clinical conundrum.
AB  - HIV complicates the diagnostic and therapeutic approaches to idiopathic
      thrombotic thrombocytopenic purpura (TTP), prompting debate in the literature
      regarding the benefit of plasma exchange versus simple plasma infusion. Herein we
      present a case of HIV-TTP, initially treated conservatively with plasma infusion
      but because of progressive neurologic decline, required urgent plasma exchange
      for resolution of hematologic derangements and neurologic sequelae. Based on the
      available literature, there appears to be a spectrum of HIV-associated TTP
      disorders. Patients with advanced HIV disease and opportunistic infections who
      present with thrombotic microangiopathy tend to respond to simple plasma
      infusion, while patients with less progressive HIV disease tend to behave like
      those with idiopathic TTP, requiring plasma exchange rather than simple plasma
      infusion. This article illustrates that in patients with HIV-TTP who do not
      respond to plasma infusion, early escalation to plasma exchange may help avoid
      life-threatening complications such as seizures and even death.

PMID- 27709660
TI  - Enlarging saphenous vein graft aneurysm.

PMID- 27709661
TI  - Edentulism and associated factors among community-dwelling middle-aged and
      elderly adults in China.
AB  - OBJECTIVE: To investigate the prevalence of self-reported edentulism and its
      associated risk factors among community-dwelling adults aged 45 years and older
      in China. MATERIALS AND METHODS: Data from the national baseline survey (2011
      2012) of the China Health and Retirement Longitudinal Study (CHARLS) were used
      for this study (N = 17 167). Bivariate and multivariate logistic regressions were
      conducted to assess the predictors of edentulism. Models 1 and 2 were based on
      the whole sample. Models 3 and 4 were based on the subsample (N = 9933) from whom
      anthropometric and blood biomarker data were available. RESULTS: The prevalence
      of edentulism was 8.64% among Chinese adults aged 45 and above. As shown by Model
      1, older age was a robust predictor for edentulism (odds ratio [OR] = 3.81 for
      people aged 55-64; OR = 11.22 for people aged 65-74; OR = 24.05 for people aged
      75 and above). Other factors positively associated with edentulism included being
      female (OR = 1.25), rural residence (OR = 1.30), asthma (OR = 1.48), depression
      (OR = 1.20), reduced physical function (OR = 1.37) and current smoking status (OR
      = 1.36). People with higher educational levels (OR = 0.75 for people who can read
      and write; OR = 0.64 for people who obtained a junior high school education or
      above) and better-off economic status (OR = 0.80) were less likely to be
      edentate. The association between edentulism and age, educational level, economic
      status and physical function remained significant in Model 3, and in addition,
      being underweight appeared as another strong predictor (OR = 1.93). CONCLUSIONS:
      The estimated prevalence of edentulism and the identified associated factors will
      provide epidemiologic evidence for future research and interventions in the
      target population in China.

PMID- 27709662
TI  - The Additive Coordination Effect on Hybrids Perovskite Crystallization and High
      Performance Solar Cell.
AB  - The coordination effects of additives during perovskite crystal growth are
      investigated, and a novel technique to fabricate high-quality perovskite thin
      films by introduction of weak coordination additives (e.g., acetonitrile) in the
      precursors is demonstrated.

PMID- 27709663
TI  - The MAPT gene is differentially methylated in the progressive supranuclear palsy
      brain.
AB  - BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative
      disease causing parkinsonian symptoms. Altered DNA methylation of the microtubule
      associated protein tau gene correlates with the expression changes in Alzheimer's
      disease and Parkinson's disease brains. However, few studies examine the
      sequences beyond the constitutive promoter. OBJECTIVES: Because activating
      different microtubule-associated protein tau gene control regions via methylation
      might regulate the differential tau expression constituting the specific
      signatures of individual tauopathies, we compared methylation of a candidate
      promoter, intron 0. METHODS: We assessed DNA methylation in the brains of
      patients with different tauopathies (35 Alzheimer's disease, 10 corticobasal
      degeneration, and 18 PSP) and 19 controls by intron 0 pyrosequencing. We also
      evaluated methylation in an independent cohort of 11 PSP cases and 12 controls.
      Frontal (affected by tau pathology) and occipital (unaffected) cortices were
      analyzed. RESULTS: In the initial samples, one CpG island site in intron 0 (CpG1)
      showed significant hypomethylation in PSP-affected frontal cortices when compared
      with controls (P = .022). Such hypomethylation was observed in replicate samples,
      but not in occipital cortices or other tauopathies. PSP and control samples
      (combining the initial and replicate samples) remained significantly different
      after adjustment for potential confounding factors (age, H1/H1 diplotype; P =
      .0005). PSP-affected tissues exhibited microtubule-associated protein tau RNA
      hyperexpression when compared with controls (P = .004), although no correlation
      with CpG1 methylation was observed. CONCLUSIONS: This exploratory study suggests
      that regions other than the constitutive promoter may be involved in microtubule
      associated protein tau gene regulation in tauopathies and that intron 0
      hypomethylation may be a specific epigenetic signature of PSP. These preliminary
      findings require confirmation. (c) 2016 International Parkinson and Movement
      Disorder Society.

PMID- 27709664
TI  - Validation rules for blood smear revision after automated hematological testing
      using Mindray CAL-8000.
AB  - BACKGROUND: This article was aimed to test the use of validation rules for blood
      smear review after automated hematological testing using Mindray CAL-8000 (two
      hematological analyzers and one autoslider). METHODS: This study was based on
      1013 peripheral blood samples (PB) referred for routine hematological testing.
      Results of testing on CAL-8000 were analyzed using both locally derived and
      International Consensus Group for Hematology (ICGH) validation rules, and then
      compared with data obtained by optical microscopy (OM). A workflow analysis was
      also completed. RESULTS: The overall agreement with locally derived and ICGH
      criteria was 91% and 85%, but a higher sensitivity was observed for locally
      derived criteria (0.97 vs 0.95). The percentage of false negative and false
      positive samples was 2.1% and 7.1% using ICGH criteria, and was 1.4% and 14%
      using locally defined rules. The throughput of CAL-8000 system was 208 samples/h,
      with a percentage of OM analysis comprised between 14% and 17%, and sensitivity
      of 0.97. As regards personnel activity, we estimated 0.8 full-time equivalent
      (FTE) of technical staff and 0.7 FTE of personnel for clinical validation of data
      and blood smear review. CONCLUSION: These results show that customization of
      validation rules is necessary for enhancing the quality of hematological testing
      and optimizing workflow.

PMID- 27709665
TI  - Essential elder endodontics.

PMID- 27709667
TI  - Tetralogy of Fallot with acquired coronary artery disease-An unusual
      presentation.
AB  - Coronary artery disease developing in tetralogy of Fallot (TOF) is rare. We
      report a rare case of TOF with acquired coronary artery disease, treated
      simultaneously with intra cardiac repair and multi vessel coronary artery bypass
      grafting.

PMID- 27709668
TI  - Luminal Clinical.

PMID- 27709669
TI  - Endoscopy Lower.

PMID- 27709666
TI  - Stop! border ahead: Automatic detection of subthalamic exit during deep brain
      stimulation surgery.
AB  - BACKGROUND: Microelectrode recordings along preplanned trajectories are often
      used for accurate definition of the subthalamic nucleus (STN) borders during deep
      brain stimulation (DBS) surgery for Parkinson's disease. Usually, the demarcation
      of the STN borders is performed manually by a neurophysiologist. The exact
      detection of the borders is difficult, especially detecting the transition
      between the STN and the substantia nigra pars reticulata. Consequently,
      demarcation may be inaccurate, leading to suboptimal location of the DBS lead and
      inadequate clinical outcomes. METHODS: We present machine-learning classification
      procedures that use microelectrode recording power spectra and allow for real
      time, high-accuracy discrimination between the STN and substantia nigra pars
      reticulata. RESULTS: A support vector machine procedure was tested on
      microelectrode recordings from 58 trajectories that included both STN and
      substantia nigra pars reticulata that achieved a 97.6% consistency with human
      expert classification (evaluated by 10-fold cross-validation). We used the same
      data set as a training set to find the optimal parameters for a hidden Markov
      model using both microelectrode recording features and trajectory history to
      enable real-time classification of the ventral STN border (STN exit). Seventy
      three additional trajectories were used to test the reliability of the learned
      statistical model in identifying the exit from the STN. The hidden Markov model
      procedure identified the STN exit with an error of 0.04 +/- 0.18 mm and detection
      reliability (error < 1 mm) of 94%. CONCLUSIONS: The results indicate that robust,
      accurate, and automatic real-time electrophysiological detection of the ventral
      STN border is feasible. (c) 2016 International Parkinson and Movement Disorder
      Society.

PMID- 27709671
TI  - Inflammatory Bowel Disease Clinical.

PMID- 27709670
TI  - Paediatrics.

PMID- 27709672
TI  - Basic Science Luminal.

PMID- 27709673
TI  - Nutrition.

PMID- 27709674
TI  - Hepatitis Viral.

PMID- 27709675
TI  - Inflammatory Bowel Disease Basic.

PMID- 27709676
TI  - Basic Science Liver.

PMID- 27709678
TI  - Gastrointestinal Cancer.

PMID- 27709677
TI  - Nursing.

PMID- 27709680
TI  - Motility/Neurogastroenterology.

PMID- 27709679
TI  - Hepatology Clinical.

PMID- 27709681
TI  - Endoscopy Upper.

PMID- 27709683
TI  - PLA2G6 mutations and Parkinsonism: Long-term follow-up of clinical features and
      neuropathology.

PMID- 27709684
TI  - Diagnostic validity of hematologic parameters in evaluation of massive pulmonary
      embolism.
AB  - BACKGROUND: The aim of this study was to determine the hematologic parameter with
      the highest diagnostic differentiation in the identification of massive acute
      pulmonary embolism (APE). METHODS: A retrospective study was performed on
      patients diagnosing with APE between June 2014 and June 2016. All radiological
      and laboratory parameters of patients were scanned through the electronic
      information management system of the hospital. PLR was obtained from the ratio of
      platelet count to lymphocyte count, NLR was obtained from the ratio of neutrophil
      count to lymphocyte count, WMR was obtained from white blood cell in mean
      platelet volume ratio, MPR was obtained from the ratio of mean platelet volume to
      platelet count, and RPR was obtained from the ratio of red distribution width to
      platelet count. RESULTS: Six hundred and thirty-nine patients consisting of 292
      males (45.7%) and 347 females (54.3%) were included in the research. Independent
      predictors of massive risk as compared to sub-massive group were; pulmonary
      arterial systolic pressure (PASP) (OR=1.40; P=.001), PLR (OR=1.59; P<.001), NLR
      (OR=2.22; P<.001), WMR (OR=1.22; P<.001), MPR (OR=0.33; P<.001), and RPR
      (OR=0.68; P<.001). Upon evaluation of the diagnostic differentiation of these
      risk factors for massive APE by employing receiver operating characteristic curve
      analysis, it was determined that PLR (AUC+/-SE=0.877+/-0.015; P<.001), and NLR
      (AUC+/-SE=0.893+/-0.013; P<.001) have similar diagnostic differentiation in
      diagnosing massive APE and these two parameters are superior over PASP, MPR, WMR,
      and RPR. CONCLUSION: We determined that the levels of NLR and PLR are superior to
      other parameters in the determination of clinical severity in APE cases.

PMID- 27709686
TI  - Perioperative mortality is the Achilles heel for cardiac transplantation in
      adults with congenital heart disease: Evidence from analysis of the UNOS
      registry.
AB  - BACKGROUND: Adults with congenital heart disease may present with end-stage heart
      failure necessitating orthotopic heart transplant (OHT). We sought to review the
      United Network for Organ Sharing (UNOS) experience with this unique cohort
      focusing on surgical outcomes and survival. METHODS: From the UNOS registry, 737
      adult congenital heart disease recipients (ACHDR) out of 26,993 OHT patients
      (2.7%) who underwent OHT were studied to analyze early and late outcomes and
      compared to non-congenital recipients (NCR) over a 15-year period (2000-2014).
      RESULTS: More ACHDR underwent OHT in the recent-era (3.1%; 2010-2014) as compared
      to the initial-era (2.5%; 2000-2004; p = 0.03). ACHDR were more likely female
      (40% vs. 24%; p < 0.01), younger (35 vs. 53 years; p < 0.01), less likely to have
      ventricular assist devices (4.2% vs. 19.3%; p < 0.01), more likely to have class
      II panel-reactive antibody >10%; p < 0.01, and were listed for a longer time (249
      vs. 181 days; p < 0.01). When compared to the NCR in the same period, the ACHDR
      cohort had longer postoperative length of stay (27 vs. 20 days; p < 0.01), higher
      operative mortality (11.5% vs. 4.6% p < 0.001), higher incidence of primary graft
      dysfunction (4.3% vs. 2.6%; p < 0.01), and higher need for dialysis (20% vs. 9%;
      p < 0.01). Primary graft dysfunction is the most common cause of death in (5.8%)
      ACHDR. Although short-term survival is poorer, long-term survival of ACHDR was
      found to be equivalent or better than NCR in long term. CONCLUSIONS:
      Perioperative morbidity and mortality adversely affects short-term survival in
      ACHDR. ACHDR who survive the first post-transplant year have equivalent or better
      long-term survival than NCR.

PMID- 27709685
TI  - Study of LRRK2 variation in tauopathy: Progressive supranuclear palsy and
      corticobasal degeneration.
AB  - BACKGROUND: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the
      most common genetic cause of Parkinson's disease (PD). Unexpectedly, tau
      pathology has been reported in a subset of LRRK2 mutation carriers. METHODS: To
      estimate the frequency of pathogenic LRRK2 mutations and to evaluate the
      association of common LRRK2 variants with risk of primary tauopathies, we studied
      1039 progressive supranuclear palsy (PSP) and 145 corticobasal degeneration
      patients from the Mayo Clinic Florida brain bank and 1790 controls ascertained at
      Mayo Clinic. Sanger sequencing of LRRK2 exons 30, 31, 35, and 41 was performed in
      all patients, and genotyping of all 17 known exonic variants with minor allele
      frequency >0.5% was performed in patients and controls. RESULTS: LRRK2 mutational
      screening identified 2 known pathogenic mutations (p.G2019S and p.R1441C), each
      in 1 PSP patient, the novel p.A1413T mutation in a PSP patient and the rare
      p.R1707K mutation in a corticobasal degeneration patient. Both p.A1413T and
      p.R1707K mutations were predicted damaging by at least 2 of 3 prediction programs
      and affect evolutionary conserved sites of LRRK2. Association analysis using
      common LRRK2 variants only showed nominal association of the p.L153L variant with
      PSP. CONCLUSIONS: Our study confirms the presence of pathogenic and potentially
      pathogenic LRRK2 mutations in pathologically confirmed primary tauopathies,
      albeit with low frequency. In contrast to PD, common LRRK2 variants do not appear
      to play a major role in determining PSP and corticobasal degeneration risk. (c)
      2016 International Parkinson and Movement Disorder Society.

PMID- 27709687
TI  - PINK1, parkin, and autophagy receptors: A new model of mitophagy.

PMID- 27709688
TI  - Twisted Polycyclic Arenes from Tetranaphthyldiphenylbenzenes by Controlling the
      Scholl Reaction with Substituents.
AB  - Herein, we report two new types of twisted polycyclic arenes (2 a, b and 3 a, b)
      with constitutionally isomeric pi-backbones, which are synthesized by controlling
      the Scholl reaction of 1,2,4,5-tetra(naphth-2-yl)-3,6-diphenylbenzene (1) with
      properly positioned electron-donating substituents. With a polycyclic backbone
      containing two [5]helicene and four [4]helicene moieties, 2 a and b are new
      members of multiple helicenes with interesting stereochemistries. The as
      synthesized 2 a and b are the twisted isomers, and thermal isomerization of
      twisted-2 b results in anti-2 b, a more stable stereoisomer. Both twisted- and
      anti-2 b have been fully characterized, and the thermal isomerization of twisted
      2 b has been studied with 1 H NMR spectroscopy and DFT calculations. Compounds 3
      a and b are new members of twistacenes, the benzannulated pentacene backbone of
      which exhibits an end-to-end twist as found from the crystal structure. Twisted-
      and anti-2 b are also found to function as p-type semiconductors in solution
      processed thin film transistors, whereas the thin films of 3 b appear insulating
      presumably due to the lack of pi-pi interactions.

PMID- 27709689
TI  - Torsional and Electronic Factors Control the C-H???O Interaction.
AB  - The precise role of non-conventional hydrogen bonds such as the C-H???O
      interaction in influencing the conformation of small molecules remains
      unresolved. Here we survey a series of beta-turn mimetics using X-ray
      crystallography and NMR spectroscopy in conjunction with quantum calculation, and
      conclude that favourable torsional and electronic effects are important for the
      population of states with conformationally influential C-H???O interactions. Our
      results also highlight the challenge in attempting to deconvolute a myriad of
      interdependent noncovalent interactions in order to focus on the contribution of
      a single one. Within a small molecule that is designed to resemble the complexity
      of the environment within peptides and proteins, the interplay of different
      steric burdens, hydrogen-acceptor/-donor properties and rotational profiles
      illustrate why unambiguous conclusions based solely on NMR chemical shift data
      are extremely challenging to rationalize.

PMID- 27709690
TI  - Weekend days are not required to accurately measure oral intake in hospitalised
      patients.
AB  - BACKGROUND: Nutrition studies in patients admitted to hospital frequently
      disregard oral intake because measurement is time-intensive and logistically
      challenging. In free-living populations, weighed food records (WFR) are the gold
      standard and are conducted on weekend and weekdays to capture variations in
      intake, although this may not translate during hospitalisation. The present study
      aimed to determine whether oral intake differs between weekends and weekdays in
      hospitalised patients. METHODS: For adult patients initially admitted to the
      intensive therapy unit with a moderate-severe head injury over a 12-month period,
      WFR were conducted each week on Tuesday, Thursday and Saturday throughout
      hospitalisation. Meal components were weighed before and after consumption, and
      energy and protein intakes were calculated using specialised software. Data are
      reported as the mean (SD). Differences were assessed using paired t-tests and
      agreement using Bland-Altman plots. RESULTS: Thirty-two patients had WFR
      collected on 220 days, 68% (n = 149) on weekdays and 32% (n = 71) on weekends.
      Overall, daily intakes were 5.72 (3.67) MJ [1367 (877) kcal] and 62 (40) g
      protein. There were no differences in intake across all days (P = 0.937 energy, P
      = 0.797 protein), nor between weekdays and weekends, in weeks 1-3 of oral intake
      (all P > 0.1). Limits of agreement between mean intakes across days were wide for
      energy [range -11.20 to 9.55 MJ (-2680 to 2283 kcal)] and protein (range -125 to
      110 g). CONCLUSIONS: Grouped energy and protein intakes from WFR in hospitalised
      patients are similar on weekdays and weekends, although large intra-patient
      variations occur. Future quantification of oral intake during hospitalisation
      should include as many days as feasible, although not necessarily weekend days,
      to reflect true intake.

PMID- 27709691
TI  - High Performance Metal Oxide-Graphene Hybrid Nanomaterials Synthesized via
      Opposite-Polarity Electrosprays.
AB  - An opposite-polarity electrospray technique is developed to synthesize Mn3 O4 
      graphene hybrid nanomaterial that shows high specific capacity, fast
      charging/discharging capability, and long cycle life for lithium storage. The
      approach offers nanoparticle size control and tunability, morphology control,
      versatility for the synthesis of different materials and hybrid structures from
      different precursors, and continuous-flow nanomanufacturing with the potential
      for full automation.

PMID- 27709692
TI  - Dermatitis, nonmelanoma skin cancer and leg ulcers.

PMID- 27709693
TI  - The prevalence and factors associated with ever perpetrating intimate partner
      violence by men receiving substance use treatment in Brazil and England: A cross
      cultural comparison.
AB  - INTRODUCTION AND AIMS: Intimate partner violence (IPV) perpetration is common
      among men who use substances. Substance use is a contributing factor for IPV
      perpetration. This cross-sectional study determined lifetime prevalence and
      factors associated with ever perpetrating IPV by men receiving substance use
      treatment in Brazil (n = 281) and England (n = 223). DESIGN AND METHODS: IPV,
      adverse childhood experiences, attitudes towards gender relations and roles,
      current health state, substance use, depressive symptoms and anger expression
      were assessed. Logistic regression determined factors associated with ever
      perpetrating any (emotional, physical and/or sexual) IPV. Multinomial logistic
      regression determined factors associated with ever perpetrating different types
      of IPV. RESULTS: 74.6% (373/500) reported ever perpetrating IPV: 16.5% (82/498)
      emotional IPV only, 46.4% (231/498) physical IPV (with/without emotional IPV) and
      11.6% (58/498) sexual IPV (with/without emotional and/or physical IPV). Higher
      anger expression, higher depressive symptoms, fighting physically with another
      man in the past year (Brazil only), experiencing a greater number of adverse
      childhood experiences and a higher hazardous drinking score (England only)
      predicted ever perpetrating IPV. Compared to never perpetrating any IPV, anger
      expression was associated with emotional and physical IPV perpetration; fighting
      physically with another man in the past year was associated with physical IPV
      perpetration and experiencing a greater number of adverse childhood experiences
      and a higher hazardous drinking score were associated with both physical and
      sexual IPV perpetration. DISCUSSION AND CONCLUSIONS: Integrated interventions
      that address IPV and substance use delivered in substance use treatment could
      improve outcomes for perpetrators and victims.[Gilchrist G, Radcliffe P, Noto AR,
      d'Oliveira AFPL. The prevalence and factors associated with ever perpetrating
      intimate partner violence by men receiving substance use treatment in Brazil and
      England: A cross-cultural comparison. Drug Alcohol Rev 2017;36:34-51].

PMID- 27709694
TI  - The brain in hypoxia; curiosity, cause and consequence.
AB  - Video slideshow introduction to the symposium by symposium organiser Damian M.
      Bailey can be found here.

PMID- 27709695
TI  - Vegetarianism and breast, colorectal and prostate cancer risk: an overview and
      meta-analysis of cohort studies.
AB  - BACKGROUND: Vegetarian diets may be associated with certain benefits toward human
      health, although current evidence is scarce and contrasting. In the present
      study, a systematic review and meta-analysis of prospective cohort studies was
      performed with respect to the association between vegetarian diets and breast,
      colorectal and prostate cancer risk. METHODS: Studies were systematically
      searched in Pubmed and EMBASE electronic databases. Eligible studies had a
      prospective design and compared vegetarian, semi- and pesco-vegetarian diets with
      a non-vegetarian diet. Random-effects models were applied to calculate relative
      risks (RRs) of cancer between diets. Statistical heterogeneity and publication
      bias were explored. RESULTS: A total of nine studies were included in the meta
      analysis. Studies were conducted on six cohorts accounting for 686 629
      individuals, and 3441, 4062 and 1935 cases of breast, colorectal and prostate
      cancer, respectively. None of the analyses showed a significant association of
      vegetarian diet and a lower risk of either breast, colorectal, and prostate
      cancer compared to a non-vegetarian diet. By contrast, a lower risk of colorectal
      cancer was associated with a semi-vegetarian diet (RR = 0.86, 95% confidence
      interval = 0.79-0.94; I2 = 0%, Pheterogeneity = 0.82) and a pesco-vegetarian diet
      (RR = 0.67, 95% confidence interval = 0.53, 0.83; I2 = 0%, Pheterogeneity = 0.46)
      compared to a non-vegetarian diet. The subgroup analysis by cancer localisation
      showed no differences in summary risk estimates between colon and rectal cancer.
      CONCLUSIONS: A summary of the existing evidence from cohort studies on vegetarian
      diets showed that complete exclusion of any source of protein from the diet is
      not associated with further benefits for human health.

PMID- 27709697
TI  - A Multi-responsive Regenerable Europium-Organic Framework Luminescent Sensor for
      Fe3+ , CrVI Anions, and Picric Acid.
AB  - A novel luminescent microporous lanthanide metal-organic framework (Ln-MOF) based
      on a urea-containing ligand has been successfully assembled. Structural analysis
      revealed that the framework features two types of 1D channels, with urea N-H
      bonds projecting into the pores. Luminescence studies have revealed that the Ln
      MOF exhibits high sensitivity, good selectivity, and a fast luminescence
      quenching response towards Fe3+ , CrVI anions, and picric acid. In particular, in
      the detection of Cr2 O72- and picric acid, the Ln-MOF can be simply and quickly
      regenerated, thus exhibiting excellent recyclability. To the best of our
      knowledge, this is the first example of a multi-responsive luminescent Ln-MOF
      sensor for Fe3+ , CrVI anions, and picric acid based on a urea derivative. This
      Ln-MOF may potentially be used as a multi-responsive regenerable luminescent
      sensor for the quantitative detection of toxic and harmful substances.

PMID- 27709696
TI  - The effect of lipid extraction on carbon and nitrogen stable isotope ratios in
      oyster tissues: Implications for glycogen-rich species.
AB  - RATIONALE: Extraction of lipids from tissues prior to carbon stable isotope
      analysis (SIA) has become a common practice, despite a lack of species-specific
      data to indicate when lipid extraction is needed. Marine invertebrates, including
      bivalves, are known to store carbon as glycogen and less in the form of lipids
      than other species, potentially reducing the need for lipid extraction even when
      C:N values are above 3.5, a value that previous studies suggest indicates a need
      for lipid extraction of animal tissues. METHODS: We investigated the need for
      lipid extraction on individual tissues (adductor muscle, gut gland, gill) and
      whole tissue of a glycogen-storing species, the oyster Crassostrea virginica.
      Bulk and lipid-extracted samples were analyzed for their C and N stable isotope
      ratios by continuous flow isotope ratio mass spectrometry (IRMS). Samples were
      analyzed on a 20-20 isotope ratio mass spectrometer (PDZ Europa) after combustion
      in an elemental analyzer (PDZ Europa Automatic Analyzer-Gas Solid Liquid).
      RESULTS: Although the C:N values for most bulk (unextracted) tissue samples were
      greater than 3.5, the lipid-extracted delta13 C values did not differ from the
      bulk values. Lipid extraction, however, affected delta15 N values in all tissue
      types except adductor muscle, indicating that separate SIA may be required when
      tissues are lipid extracted. CONCLUSIONS: These data demonstrate that it is not
      necessary to lipid extract oyster tissues in all cases, and that C:N thresholds
      for lipid extraction in other species may not be reliable for organisms such as
      oysters that store glycogen. Our data indicate that minimizing unnecessary lipid
      extraction through preliminary testing will save researchers time and expense by
      avoiding superfluous sample handling, reducing concern over secondary effects on
      data quality, and reducing the costs of reagents and additional separate stable
      isotope analysis to ensure analytical accuracy. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27709698
TI  - Contact allergy to 1,2-benzisothiazolin-3-one.

PMID- 27709699
TI  - Patch testing with used and unused personal products: a practical way to show
      contamination with contact allergens.

PMID- 27709700
TI  - Four cases of allergic contact dermatitis caused by
      methylchloroisothiazolinone/methylisothiazolinone in ironing water.

PMID- 27709701
TI  - Please, label the label; a case report of occupational allergic contact
      dermatitis caused by methylisothiazolinone in adhesive labels.

PMID- 27709702
TI  - Allergic contact dermatitis caused by
      methylchloroisothiazolinone/methylisothiazolinone in a medical device.

PMID- 27709703
TI  - Methylisothiazolinone contact allergy - are rinse-off cosmetics and household
      products relevant sources of exposure?

PMID- 27709704
TI  - What lash stylists and dermatologists should know!

PMID- 27709707
TI  - Methylisothiazolinone, quo vadis?

PMID- 27709705
TI  - Undisclosed presence of methylisothiazolinone in '100% natural' Konjac(r) sponge.

PMID- 27709706
TI  - Methylisothiazolinone in a designer spectacle frame - a surprising finding.

PMID- 27709708
TI  - An intriguing occupational atypical dermatitis with respiratory symptoms.

PMID- 27709709
TI  - Allergic contact dermatitis caused by ultrasonic gel: is this possible for a
      hypoallergenic gel?

PMID- 27709710
TI  - Allergic contact dermatitis caused by the preservative 4,5-dichloro-2-n-octyl-4
      isothiazolin-3-one in black trousers.

PMID- 27709711
TI  - Ferroelectric Control of Organic/Ferromagnetic Spinterface.
AB  - Organic multiferroic tunnel junctions based on La0.6 Sr0.4 MnO3 /poly(vinylidene
      fluoride) (PVDF)/Co structures are fabricated. The tunneling magneto-resistance
      sign can be changed by electrically switching the ferroelectric polarization of
      PVDF barrier. It is demonstrated that the spin-polarization of the PVDF/Co
      spinterface can be actively controlled by tuning the ferroelectric polarization
      of PVDF. This study opens new functionality in controlling the injection of spin
      polarization into organic materials via the ferroelectric polarization of the
      barrier.

PMID- 27709712
TI  - Hydroperoxyl Radicals (HOO. ): Vitamin E Regeneration and H-Bond Effects on the
      Hydrogen Atom Transfer.
AB  - Hydroperoxyl (HOO. ) and alkylperoxyl (ROO. ) radicals show a different behavior
      in H-atom-transfer processes. Both radicals react with an analogue of alpha
      tocopherol (TOH), but HOO. , unlike ROO. , is able to regenerate TOH by a fast H
      atom transfer: TO. +HOO. ->TOH+O2 . The kinetic solvent effect on the H-atom
      transfer from TOH to HOO. is much stronger than that observed for ROO. because
      noncovalent interactions with polar solvents (Solv???HOO. ) destabilize the
      transition state.

PMID- 27709713
TI  - N-Heterocyclic Silylenes in Boron Chemistry: Facile Formation of Silylboranes and
      Silaborinines.
AB  - Reaction of a N-heterocyclic silylene (NHSi) with PhBX2 (X=Cl, Br) readily
      afforded six-membered silaborinines through an insertion/ring expansion sequence.
      Increasing the sterics of the borane from phenyl to duryl enabled the selective
      generation and isolation of the highly colored silylborane intermediates.
      Theoretical studies on the mechanism and energetics of the silaborinine formation
      were fully consistent with the experimental observations.

PMID- 27709714
TI  - Using longitudinal mixed methods to study the development of professional
      behaviours during pharmacy work-based training.
AB  - Recent longitudinal investigations of professional socialisation and development
      of professional behaviours during work-based training are lacking. Using
      longitudinal mixed methods, this study aimed to explore the development of
      professional behaviours during a year of intensive work-based (pre-registration)
      training in pharmacy. Twenty trainee pharmacists and their tutors completed semi
      structured interview and professional behaviour questionnaires at four time
      points during 2011/2012: months 1, 4 and 9 during training and 4 months after
      registration; tutors participated in months 1 and 9. Interviews were analysed
      thematically using template analysis, and questionnaires were analysed using
      ANOVA and t-tests. Self-assessed (trainee) and tutor ratings of all elements of
      professional behaviours measured in questionnaires (appearance,
      interpersonal/social skills, responsibility, communication skills) increased
      significantly from the start of pre-registration training to post-registration.
      Some elements, for example, communication skills, showed more change over time
      compared with others, such as appearance, and continued to improve post
      registration. Qualitative findings highlighted the changing roles of trainees and
      learning experiences that appeared to facilitate the development of professional
      behaviours. Trainees' colleagues, and particularly tutors, played an essential
      part in trainees' development through offering support and role modelling.
      Trainees noted that they would have benefited from more responsibilities during
      training to ease the transition into practising as a responsible pharmacist.
      Longitudinal mixed methods can unpack the way in which professional behaviours
      develop during work-based training and allow researchers to examine changes in
      the demonstration of professional behaviours and how they occur. Identifying
      areas less prone to change allows for more focus to be given to supporting
      trainees in areas where there is a development need, such as communication skills
      and holding increasing responsibility.

PMID- 27709715
TI  - Carbon Nanotube/Boron Nitride Nanocomposite as a Significant Bifunctional
      Electrocatalyst for Oxygen Reduction and Oxygen Evolution Reactions.
AB  - It is an immense challenge to develop bifunctional electrocatalysts for oxygen
      reduction reactions (ORR) and oxygen evolution reactions (OER) in low temperature
      fuel cells and rechargeable metal-air batteries. Herein, a simple and cost
      effective approach is developed to prepare novel materials based on carbon
      nanotubes (CNTs) and a hexagonal boron nitride (h-BN) nanocomposite (CNT/BN)
      through a one-step hydrothermal method. The structural analysis and morphology
      study confirms the formation of a homogeneous composite and merging of few
      exfoliated graphene layers of CNTs on the graphitic planes of h-BN, respectively.
      Moreover, the electrochemical study implies that CNT/BN nanocomposite shows a
      significantly higher ORR activity with a single step 4-electron transfer pathway
      and an improved onset potential of +0.86 V versus RHE and a current density of
      5.78 mA cm-2 in alkaline conditions. Interestingly, it exhibits appreciably
      better catalytic activity towards OER at low overpotential (eta=0.38 V) under
      similar conditions. Moreover, this bifunctional catalyst shows substantially
      higher stability than a commercial Pt/C catalyst even after 5000 cycles.
      Additionally, this composite catalyst does not show any methanol oxidation
      reactions that nullify the issues due to fuel cross-over effects in direct
      methanol fuel cell applications.

PMID- 27709716
TI  - Room-Temperature Synthesis of Covalent Organic Frameworks with a Boronic Ester
      Linkage at the Liquid/Solid Interface.
AB  - With various prospected applications in the field of nanoelectronics and
      catalysis, on-surface synthesis of single-layer covalent organic frameworks
      (surface COFs) with designable structures and properties have attracted enormous
      interest. Herein, we report on a scanning tunneling microscopic investigation of
      the surface-confined synthesis of a covalently bonded boronic ester network
      directly at the octanoic acid/ highly oriented pyrolytic graphite(HOPG) interface
      under room temperature. The dynamic reaction process was investigated in detail.
      STM results indicate that the surface networks undergo structural evolution from
      a hybrid covalent/noncovalent multiwall porous network to single-wall hexagonal
      COF with the decrease of monomer concentration. Further experimental observation
      disclosed that the boronic ester-linked system is sensitive to instantaneous
      voltage pulses and the stimulation of the STM tip. In addition, the 1 H NMR
      spectra has further confirmed that the surface and octanoic acid may play
      important roles in promoting the reaction between 4,4'-phenylazobenzoyl diboronic
      acid (ABBA) and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) building units.

PMID- 27709717
TI  - Changing the balance of social care for older people: simulating scenarios under
      demographic ageing in New Zealand.
AB  - The demographic ageing of New Zealand society, as elsewhere in the developed
      world, has dramatically increased the proportion of older people (aged 65 years
      and over) in the population. This has major policy implications for the future
      organisation of social care. Our objective was to test the effects on social care
      use, first, of putative changes in the overall disability profile of older
      people, and second, of alterations to the balance of their care, i.e. whether it
      was community-based or residential. In order to undertake these experiments, we
      developed a microsimulation model of the later life course using individual-level
      data from two official national survey series on health and disability,
      respectively, to generate a synthetic version which replicated original data and
      parameter settings. A baseline projection under current settings from 2001 to
      2021 showed moderate increases in disability and associated social care use.
      Artificially decreasing disability levels, below the baseline projection, only
      moderately reduced the use of community care (both informal and formal).
      Scenarios implemented by rebalancing towards informal care use moderately reduced
      formal care use. However, only moderate compensatory increases in community-based
      care were required to markedly decrease the transition to residential care. The
      disability impact of demographic ageing may not have a major negative effect on
      system resources in developed countries like New Zealand. As well as healthy
      ageing, changing the balance of social care may alleviate the impact of
      increasing demand due to an expanding population of older people.

PMID- 27709718
TI  - Body composition assessed by dual-energy X-ray absorptiometry predicts early
      infectious complications after liver transplantation.
AB  - BACKGROUND: It is challenging to identify malnutrition, which is a risk factor
      for poor outcome in patients with liver cirrhosis. In the present study, we aimed
      to investigate the prevalence of malnutrition among patients listed for liver
      transplantation, as assessed by different methods, and also to relate dual-energy
      X-ray absorptiometry (DXA) to short-term post-transplant outcomes. METHODS: In
      this retrospective cohort study, we reviewed the medical records of 106 patients
      who underwent liver transplantation in 2009-2012. Body composition was assessed
      by the fat-free mass index (FFMI) and fat mass index (FMI) obtained using DXA.
      Severe infections within 1 month, length of stay in intensive care unit and
      length of hospital stay were endpoints of primary interest. RESULTS: The
      prevalence of malnutrition was 2-20% depending on sex and the assessment method.
      Thirty-nine (37%) patients developed severe infections within 1 month after liver
      transplantation. In multivariate analysis with logistic regression, body
      composition was significantly associated with post-operative infection when
      measured with FFMI (P = 0.043) but not with FMI (P = 0.087). Post-operative
      dialysis (P = 0.004) and post-operative infections (P < 0.001) were significantly
      associated with length of stay in hospital. Post-operative bleeding (P = 0.015),
      duration of mechanical ventilation (P < 0.001) and the need for dialysis (P <
      0.001), but not body composition, were significant predictors of the length of
      stay in the intensive care unit. CONCLUSIONS: The prevalence of malnutrition
      depends on assessment method. FFMI is an independent predictor for early post
      transplant infections. Body composition measured by DXA during the pretransplant
      evaluation provides valuable information about nutritional status in patients
      with liver cirrhosis.

PMID- 27709719
TI  - Natural Abundance 15 N and 13 C Solid-State NMR Chemical Shifts: High Sensitivity
      Probes of the Halogen Bond Geometry.
AB  - Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a versatile
      characterization technique that can provide a plethora of information
      complementary to single crystal X-ray diffraction (SCXRD) analysis. Herein, we
      present an experimental and computational investigation of the relationship
      between the geometry of a halogen bond (XB) and the SSNMR chemical shifts of the
      non-quadrupolar nuclei either directly involved in the interaction (15 N) or
      covalently bonded to the halogen atom (13 C). We have prepared two series of X
      bonded co-crystals based upon two different dipyridyl modules, and several
      halobenzenes and diiodoalkanes, as XB-donors. SCXRD structures of three novel co
      crystals between 1,2-bis(4-pyridyl)ethane, and 1,4-diiodobenzene, 1,6
      diiodododecafluorohexane, and 1,8-diiodohexadecafluorooctane were obtained. For
      the first time, the change in the 15 N SSNMR chemical shifts upon XB formation is
      shown to experimentally correlate with the normalized distance parameter of the
      XB. The same overall trend is confirmed by density functional theory (DFT)
      calculations of the chemical shifts. 13 C NQS experiments show a positive, linear
      correlation between the chemical shifts and the C-I elongation, which is an
      indirect probe of the strength of the XB. These correlations can be of general
      utility to estimate the strength of the XB occurring in diverse adducts by using
      affordable SSNMR analysis.

PMID- 27709720
TI  - Differential micro ribonucleic acid expression profiling in ovarian endometrioma
      with leuprolide acetate treatment.
AB  - AIM: Micro ribonucleic acids (miRNAs) play an important pathological role in
      endometriosis. Leuprolide acetate, an analog of gonadotropin-releasing hormone,
      is widely used to treat endometriosis; however, the molecular mechanisms involved
      in endometriotic tissue regression remain unclear. We performed miRNA expression
      profiling of clinical ovarian endometrioma to obtain insight into the effects of
      leuprolide acetate treatment. METHODS: We obtained clinical samples from nine
      normal eutopic endometrium, eight ovarian endometriotic, and 12 leuprolide
      acetate-treated endometriotic tissues. We compared the miRNA expression profiles
      of the three groups by performing TaqMan Array MicroRNA Card and bioinformatic
      analysis. RESULTS: Two miRNAs, miR-939 and miR-154, were upregulated in
      endometriotic tissue and downregulated in leuprolide acetate-treated
      endometriotic tissue. Five miRNAs (miR-146a, miR-142-3p, miR-136*, miR-125b-1*
      and miR-15b*) were unchanged in endometriotic tissue but were upregulated under
      leuprolide acetate treatment. Ingenuity pathway analysis using predicted target
      genes for the seven identified miRNAs suggested the involvement of a range of
      pathways, including axonal guidance, bone morphogenetic protein, phosphatase and
      tensin homolog and nitric oxide signaling; molecular mechanisms of cancer; and
      the adipogenesis and signal transducer and activator of transcription 3 (STAT3)
      pathways. CONCLUSIONS: To our knowledge, this is the first report profiling the
      miRNAs of endometrioma under leuprolide acetate treatment. The expression of
      seven miRNAs was modulated, concomitant with the disease state. This result gives
      new insight into the effects of leuprolide acetate treatment. Further
      investigation using quantitative reverse transcriptase-polymerase chain reaction
      and immunohistochemistry will allow us to validate the results of this study and
      to explore new therapeutic targets and biomarkers of endometriosis.

PMID- 27709721
TI  - Periphery-Functionalized Porous Organic Cages.
AB  - By synthesizing derivatives of a trans-1,2-diaminocyclohexane precursor, three
      new functionalized porous organic cages were prepared with different chemical
      functionalities on the cage periphery. The introduction of twelve methyl groups
      (CC16) resulted in frustration of the cage packing mode, which more than doubled
      the surface area compared to the parent cage, CC3. The analogous installation of
      twelve hydroxyl groups provided an imine cage (CC17) that combines permanent
      porosity with the potential for post-synthetic modification of the cage exterior.
      Finally, the incorporation of bulky dihydroethanoanthracene groups was found to
      direct self-assembly towards the formation of a larger [8+12] cage, rather than
      the expected [4+6], cage molecule (CC18). However, CC18 was found to be non
      porous, most likely due to cage collapse upon desolvation.

PMID- 27709722
TI  - Cardiogenic shock in intensive care units: evolution of prevalence, patient
      profile, management and outcomes, 1997-2012.
AB  - AIM: To address the paucity of data on the characteristics, outcome and temporal
      trends in mortality of cardiogenic shock (CS) patients admitted to intensive care
      units (ICUs) we examined key features, variations in mortality from CS, and
      predictors of death in ICU patients over the past 15 years. METHODS AND RESULTS:
      From the 1997-2012 database of the College des Utilisateurs de Bases de donnees
      en Reanimation (CUB-Rea) that prospectively collects data from ICUs in the
      greater Paris area, we determined temporal trends in the incidence of CS, patient
      outcomes [Crude and Simplified Acute Physiology Score (SAPS)-II Standardized
      Mortality] and predictors of in-ICU mortality. Of the 316 905 ICU admissions, 19
      416 (6.1%) exhibited CS, with incidence increasing from 4.1% to 7.7% (P < 0.001).
      Over time, the age of admitted patients decreased by 2.7 years [95% confidence
      interval (CI), -2.0 to -3.4] and SAPS-II increased by 5.8% (95% CI 4.8-6.8) from
      58.7 +/- 25.3 to 64.5 +/- 23.3 (P < 0.001). Crude in-ICU mortality declined from
      50% to 45% (-5.6%; 95% CI -7.7 to -3.5) as SAPS-II Standardized ICU mortality
      rates decreased from 56.5% to 44.2% (P < 0.001). A more recent time-period was an
      independent correlate of decreased mortality in multivariate analyses. The
      decrease in mortality rate was more marked in patients with decompensated heart
      failure, cardiac arrest, or acute myocardial infarction. CONCLUSIONS: Patients
      with CS represent a greater proportion of patients admitted to ICUs over the past
      15 years, having become younger but more critically ill. Although their mortality
      has decreased, suggesting improved overall patient management, it remains
      particularly high, warranting further research specifically focused on this
      population.

PMID- 27709723
TI  - Road map for improvement: Point prevalence audit and survey of central venous
      access devices in paediatric acute care.
AB  - AIM: To identify the prevalence, management and complications associated with
      central venous access devices (CVADs) within Australian paediatric facilities,
      providing a map for clinicians, researchers and managers to focus solutions.
      METHODS: A point prevalence audit and survey of CVAD practices in Australian
      tertiary paediatric hospitals between September and November 2015, using
      validated data collection tools. RESULTS: Across the six sites, 1027 patients
      were screened with CVADs prevalent in 26.1% (n = 268), and 261 CVADs in 248
      patients available for audit. Variations in management were evident with
      dressings not meeting the basic criteria of clean, dry and intact for 13.5% of
      CVADs (n = 35), and non-sterile dressings used to reinforce 26.4% of CVADs (n =
      69). Almost half of CVADs (49.4%; n = 132) had no documentation regarding site
      assessment in the previous 4 h, and 13.4% had no planned use in the next 24 h (35
      CVAD). CVAD-associated complications within the previous 7 days were evident in
      9.5% of CVADs (n = 27), most commonly catheter blockage (5.7% CVAD, n = 15), and
      bloodstream infection (1.9% CVAD, n = 5). Peripherally inserted central catheters
      (16.9%) in comparison to other catheter types (7.4%; P = 0.04), and subsequent
      CVADs (14.1%) in comparison to initial CVADs (6.5%; P = 0.04), had significantly
      higher proportions of CVAD-associated complications in the previous 7 days.
      Variation between the sites' guidelines was evident across many practices.
      CONCLUSIONS: CVADs are prevalent and essential for paediatric health care;
      however, complications remain a significant problem. Areas identified for
      improvement were local CVAD guidelines, regular documentation of CVAD site
      assessment and review of dressing products to improve integrity.

PMID- 27709724
TI  - Theoretical approaches of online social network interventions and implications
      for behavioral change: a systematic review.
AB  - RATIONAL, AIMS AND OBJECTIVES: The aim of this review was to identify general
      theoretical frameworks used in online social network interventions for behavioral
      change. To address this research question, a PRISMA-compliant systematic review
      was conducted. METHODS: A systematic review (PROSPERO registration number
      CRD42014007555) was conducted using 3 electronic databases (PsycINFO, Pubmed, and
      Embase). Four reviewers screened 1788 abstracts. RESULTS: 15 studies were
      selected according to the eligibility criteria. Randomized controlled trials and
      controlled studies were assessed using Cochrane Collaboration's "risk-of-bias"
      tool, and narrative synthesis. Five eligible articles used the social cognitive
      theory as a framework to develop interventions targeting behavioral change. Other
      theoretical frameworks were related to the dynamics of social networks, intention
      models, and community engagement theories. Only one of the studies selected in
      the review mentioned a well-known theory from the field of health psychology.
      CONCLUSION: Conclusions were that guidelines are lacking in the design of online
      social network interventions for behavioral change. Existing theories and models
      from health psychology that are traditionally used for in situ behavioral change
      should be considered when designing online social network interventions in a
      health care setting.

PMID- 27709725
TI  - Exploring Canadian surgeons' decisions about postoperative weight bearing for
      their hip fracture patients.
AB  - For older adults with osteoporosis, a fall resulting in hip fracture is a life
      changing event from which only one-third fully recover. Current best evidence
      argues strongly for elderly patients to bear weight on their repaired hip
      fracture immediately after their surgery to maximize their chances of full or
      nearly full recovery. Patient stakeholders in Canada have argued that some
      surgeons fail to issue "weight-bearing-as-tolerated" (WBAT) orders in all
      eligible cases, protecting their bony repair but contributing to increased
      mortality and long-term disability rates. In collaboration with a national
      stakeholder organization, Bone and Joint Canada, we interviewed 20 orthopedic
      surgeons across Canada who perform hip fracture repair surgery, with the aim of
      understanding their attitudes and behavior toward patient management regarding
      weight bearing. Qualitative content analysis, in which themes are identified and
      agreed by multiple coders, suggested that both patient characteristics and
      surgeon factors influence surgeons' postoperative weight-bearing orders. While
      almost all respondents agreed that weight bearing as tolerated is indeed
      therapeutic for most hip fracture repair or replacement patients, surgeons also
      described certain patient characteristics that would diminish the value of
      immediate weight bearing, including poor bone quality and certain types of
      fracture pattern. Surgeon factors that affect postoperative mobilization orders
      include choice of construct, previous experience of construct failure, and lack
      of local audit data regarding past weight-bearing decisions and patient outcomes.
      Thus, although familiar with best practice guidelines, surgeons also have "rules
      to break the rules." In an era when "good" medicine leans toward science rather
      than art, the role of individual experience in decision making with regard to hip
      fracture care continues to be important and would benefit from being discussed
      openly.

PMID- 27709726
TI  - Anti-Campylobacter activity of resveratrol and an extract from waste Pinot noir
      grape skins and seeds, and resistance of Camp. jejuni planktonic and biofilm
      cells, mediated via the CmeABC efflux pump.
AB  - AIMS: To define anti-Campylobacter jejuni activity of an extract from waste skins
      and seeds of Pinot noir grapes (GSS), resveratrol and possible resistance
      mechanisms, and the influence of these on Camp. jejuni morphology. METHODS AND
      RESULTS: Using gene-specific knock-out Camp. jejuni mutants and an efflux pump
      inhibitor, we showed CmeABC as the most active efflux pump for extrusion across
      the outer membrane of GSS extract and resveratrol. Using polystyrene surface and
      pig small intestine epithelial (PSI) and human foetal small intestine (H4) cell
      lines, GSS extract shows an efficient inhibition of adhesion of Camp. jejuni to
      these abiotic and biotic surfaces. CONCLUSIONS: Low doses of GSS extract can
      inhibit Camp. jejuni adhesion to polystyrene surfaces and to PSI and H4 cells,
      and can thus modulate Camp. jejuni invasion and intracellular survival.
      SIGNIFICANCE AND IMPACT OF THE STUDY: An understanding of the activities of GSS
      extract and resveratrol as bacterial growth inhibitors and the specific
      mechanisms of cell accumulation is crucial for our understanding of Camp. jejuni
      resistance. GSS extract inhibition of Camp. jejuni adhesion to abiotic and biotic
      surfaces provides a further step towards the application of new innovative
      strategies to control Campylobacter contamination and infection via the food
      chain.

PMID- 27709727
TI  - Leaf spot disease adversely affects human health-promoting constituents and
      withanolide biosynthesis in Withania somnifera (L.) Dunal.
AB  - AIMS: The present work investigates the implication of leaf spot disease on the
      antioxidant potential and commercial value of pharmaceutically important
      constituents of Withania somnifera, a high-valued medicinal plant. METHODS AND
      RESULTS: Leaf spot disease was induced in W. somnifera by inoculating Alternaria
      alternata (Fr.) Keiss. pathogen. Total polyphenolic content and antioxidant
      potential showed a significant decrease during leaf spot disease. Evaluation of
      pharmaceutically active constituents withaferin A, withanone and withanolide A
      utilizing high-performance liquid chromatography showed a significant decrease in
      diseased samples as compared to healthy ones. Quantitative expression of major
      genes involved in withanolide biosynthesis also showed down-regulation in
      diseased samples. Alterations in the ultra-structure of chloroplasts were also
      analysed under transmission electron microscopy to get a better insight into the
      changes of withanolide biosynthesis in leaf during disease infestation.
      CONCLUSIONS: The present work suggests that when the pathogenic fungus invades
      the host plants, it evokes multiple responses, which could be studied at various
      levels. The knowledge gained from this work will provide appropriate rationale
      for controlling the bio-deterioration of the pharmaceutically active metabolites
      in W. somnifera and development of suitable strategies against leaf spot disease.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to investigate the
      effect of leaf spot disease on the human health-promoting constituents and
      withanolide biosynthesis in this high-valued medicinal plant.

PMID- 27709728
TI  - C-terminal domains of bacterial proteases: structure, function and the
      biotechnological applications.
AB  - C-terminal domains widely exist in the C-terminal region of multidomain
      proteases. As a beta-sandwich domain in multidomain protease, the C-terminal
      domain plays an important role in proteolysis including regulation of the
      secretory process, anchoring and swelling the substrate molecule, presenting as
      an inhibitor for the preprotease and adapting the protein structural flexibility
      and stability. In this review, the diversity, structural characteristics and
      biological function of C-terminal protease domains are described. Furthermore,
      the application prospects of C-terminal domains, including polycystic kidney
      disease, prepeptidase C-terminal and collagen-binding domain, in the area of
      medicine and biological artificial materials are also discussed.

PMID- 27709729
TI  - Study on differentiation during embryonic development across selective and
      ancestral breeds.
AB  - In order to explore the effect of strain on diverging post-hatch muscle
      properties, muscle regulation during embryo development was investigated in
      selected and unselected breeds. Four broiler strains were used: JingNing (JN)
      chicken (a Chinese native chicken), HuangYu (HY) broiler, BaiYu (BY) broiler and
      Hyline layer (commercial crossbred chickens). Results showed that the four breeds
      had almost the same characteristic during different incubation periods. BY
      broilers moved more than JN and Hyline layers from Hamburger & Hamilton stage
      (HH)24 to HH31 (P < 0.05). HY broilers moved more than JN and Hyline layers from
      HH27 to HH31 (P < 0.01). All the embryos were heavier daily from HH24 to ED18 (P
      < 0.05); broilers presented greater body weights than JN and hyline layers (P >
      0.05); broilers presented smaller fiber diameter than JN chickens before HH31 (P
      > 0.05). From then on, JN chicken exhibited smaller fiber diameter compared to
      the broilers (P > 0.05). Western blotting indicated all the breeds had continuous
      insulin-like growth factor-I (IGF-I) expression, with the highest expression
      level in broilers from HH19 to HH24 and highest expression level in JN chicks
      from HH27 to HH31. The results indicated that the diverging growth among breeds
      was already shown in embryonic stages; the different expression patterns of IGF-I
      may be involved in cell proliferation and differentiation.

PMID- 27709731
TI  - Seeking Applicants for New Trans NIH K12 Program in Emergency Care Research.

PMID- 27709730
TI  - Histological and ultrastructural features of the rectum in Poecilimon cervus
      Karabag, 1950 (Orthoptera: Tettigoniidae).
AB  - The morphology and ultrastructure of the rectum in Poecilimon cervus Karabag,
      1950 (Orthoptera, Tettigoniidae) were analyzed by light microscope, scanning
      (SEM) and transmission electron microscopes (TEM). The rectum is the final part
      of the digestive tract that plays an important role in water reabsorption in
      insects and so provides osmoregulation. In the transverse sections, six rectal
      pads and columnar epithelium can be distinguished. The cuticular intima lines the
      lumen at the apical side of the epithelium. In the cytoplasm, there are numerous
      mitochondria, some endocytic vesicles, secreting vesicles whose sizes differ
      according to the area in the cell, and a nucleus with globular in shape. With
      this study, we aimed to demonstrate the ultrastructure of the rectum of P. cervus
      and differences or similarities of with other species.

PMID- 27709732
TI  - Mucous membrane pemphigoid reactive only with BP230.

PMID- 27709735
TI  - Octulene: A Hyperbolic Molecular Belt that Binds Chloride Anions.
AB  - Octulene, the higher homologue of kekulene and septulene, was synthesized using
      the fold-in method. This new hydrocarbon macrocycle contains a large 24-membered
      inner circuit, which is peripherally fused to 24 benzene rings. Such an
      arrangement produces considerable hyperbolic distortion of the pi-conjugated
      surface. The consequences of distortion in octulene were explored using
      photophysical methods, which revealed a reduced electronic band gap and greater
      flexibility of the pi system. Octulene contains a functional cavity with a
      diameter larger than 5.5 A that is capable of efficiently binding the chloride
      anion in a nonpolar solvent (Ka = 2.2(4)*104  m-1 , 1 % dichloromethane (DCM) in
      benzene). The octulene-chloride interaction is stabilized by eight weak C(sp2
      )H???Cl bonds, providing the first example of a hydrocarbon-based anion receptor.

PMID- 27709734
TI  - What factors influence successful recruitment of siblings of individuals with
      first episode psychosis to e-health interventions? A qualitative study.
AB  - BACKGROUND: Recruitment to clinical research studies can prove complex. This is
      particularly true of mental health research, given factors such as
      confidentiality, capacity and consent, or when attempting to recruit family
      members as opposed to service users themselves. AIM: This study investigated the
      challenges experienced and strategies employed in the recruitment of siblings of
      people with first episode psychosis using Early Intervention in Psychosis
      Services (EIPS) in England. METHODS: As part of a randomized controlled trial
      (RCT) of an e-health intervention for siblings, we conducted a process evaluation
      study whereby semistructured interview was undertaken with clinical and research
      staff involved in recruitment of siblings. Data were analysed thematically.
      RESULTS: Twelve participants from six EIPS were interviewed. Data analysis
      revealed seven key themes: (i) limited comprehensive family data available; (ii)
      data governance and consent issues; (iii) organizational factors; (iv) convoluted
      recruitment methods; (v) concerns about service users' opinions; (vi) fluidity in
      siblings' needs and expectations; and (vii) strategies to enhance recruitment.
      CONCLUSIONS: Recruitment challenges identified in this study concerned
      administrative, organizational, process and attitudinal issues. These are similar
      to other studies recruiting mental health service users as well as family
      members. Failure to recruit to target implies that studies are underpowered to
      detect potential statistically or clinically meaningful changes. Future studies
      should establish how best to enhance family inclusiveness in clinical practice
      and research.

PMID- 27709733
TI  - EGF-Amphiregulin Interplay in Airway Stem/Progenitor Cells Links the Pathogenesis
      of Smoking-Induced Lesions in the Human Airway Epithelium.
AB  - The airway epithelium of cigarette smokers undergoes dramatic remodeling with
      hyperplasia of basal cells (BC) and mucus-producing cells, squamous metaplasia,
      altered ciliated cell differentiation and decreased junctional barrier integrity,
      relevant to chronic obstructive pulmonary disease and lung cancer. In this study,
      we show that epidermal growth factor receptor (EGFR) ligand amphiregulin (AREG)
      is induced by smoking in human airway epithelium as a result of epidermal growth
      factor (EGF)-driven squamous differentiation of airway BC stem/progenitor cells.
      In turn, AREG induced a unique EGFR activation pattern in human airway BC,
      distinct from that evoked by EGF, leading to BC- and mucous hyperplasia, altered
      ciliated cell differentiation and impaired barrier integrity. Further, AREG
      promoted its own expression and suppressed expression of EGF, establishing an
      autonomous self-amplifying signaling loop in airway BC relevant for promotion of
      EGF-independent hyperplastic phenotypes. Thus, EGF-AREG interplay in airway BC
      stem/progenitor cells is one of the mechanisms that mediates the interconnected
      pathogenesis of all major smoking-induced lesions in the human airway epithelium.
      Stem Cells 2017;35:824-837.

PMID- 27709737
TI  - A multicenter study on the validation of the Burnout Battery: a new visual analog
      scale to screen job burnout in oncology professionals.
AB  - OBJECTIVES: The objective of the study is to develop a novel tool-the Burnout
      Battery-for briefly screening burnout among oncology professionals in China and
      assessing its validity. METHODS: A multicenter study was conducted in doctors and
      nurses of the oncology departments in China from November 2014 to May 2015. The
      Burnout Battery was administered with the Maslach Burnout Inventory-Human
      Services Survey (MBI-HSS) and the Doctors' Job Burnout Questionnaire. RESULTS: Of
      538 oncology doctors and nurses who completed all the survey, using MBI-HSS as
      the standard tool for measuring burnout, 52% had emotional exhaustion, 39.4% had
      depersonalization, and 59.3% had a low sense of personal accomplishment. Receiver
      operating characteristic curve analyses showed that the best cut-off of the
      Burnout Battery was the battery with 3 bars, which yielded best sensitivity and
      specificity against all the 3 subscales of MBI-HSS. With this cut-off, nearly
      half of Chinese oncology professionals (46.8%) had burnout. The Burnout Battery
      correlated significantly with subscales of the MBI-HSS and the Doctors' Job
      Burnout Questionnaire. In multiple logistic regression analysis, those who worked
      more than 60 hours per week and who thought clinical work was the most stressful
      part of their job were more likely to experience burnout. CONCLUSION: Chinese
      oncology professionals exhibit high levels of burnout. The Burnout Battery
      appears to be a simple and useful tool for screening burnout. Working long hours
      and perceiving clinical work as the most stressful part of the job were the main
      factors associated with burnout.

PMID- 27709736
TI  - Generation of Functional Human Retinal Ganglion Cells with Target Specificity
      from Pluripotent Stem Cells by Chemically Defined Recapitulation of Developmental
      Mechanism.
AB  - Glaucoma is a complex group of diseases wherein a selective degeneration of
      retinal ganglion cells (RGCs) lead to irreversible loss of vision. A
      comprehensive approach to glaucomatous RGC degeneration may include stem cells to
      functionally replace dead neurons through transplantation and understand RGCs
      vulnerability using a disease in a dish stem cell model. Both approaches require
      the directed generation of stable, functional, and target-specific RGCs from
      renewable sources of cells, that is, the embryonic stem cells and induced
      pluripotent stem cells. Here, we demonstrate a rapid and safe, stage-specific,
      chemically defined protocol that selectively generates RGCs across species,
      including human, by recapitulating the developmental mechanism. The de novo
      generated RGCs from pluripotent cells are similar to native RGCs at the
      molecular, biochemical, functional levels. They also express axon guidance
      molecules, and discriminate between specific and nonspecific targets, and are
      nontumorigenic. Stem Cells 2017;35:572-585.

PMID- 27709739
TI  - Perineural invasion on biopsy is associated with upstaging at radical
      prostatectomy in Gleason score 3 + 4 = 7 prostate cancer.
AB  - This study assesses if perineural invasion (PNI) detected on biopsy with Gleason
      score (GS) 3 + 4 = 7 prostate cancer (PCa) is associated with upstaging/upgrading
      of disease after radical prostatectomy (RP). 154 patients with GS 3 + 4 = 7 PCa
      diagnosed from biopsy who underwent RP were assessed for PNI. The percentage of
      biopsy sites with PNI (%PNI) was also calculated. Pattern 4 morphologies (ill
      defined glands [IDG], fused, cribriform, and glomerulations) were also assessed.
      Clinical information, GS and stage after RP were retrieved from the medical
      records. 45 % (69/154) of patients were upstaged (>=pT3) and 29 % (44/154) were
      upgraded to GS >3 + 4 = 7 after RP. 37 % (57/154) of patients had PNI which was
      associated with upstaging (RR 1.4; P = 0.04) but not upgrading (RR 0.9; P = 0.7).
      There was higher %PNI in upstaged patients (12.1 % +/- 1.8 vs. 7.1 % +/- 1.5, P =
      0.03) with a significant correlation between %PNI and >=pT3 (r = 0.178, P =
      0.027). After multivariate analysis, only cribriform formations were
      significantly associated with upstaging (P = 0.009). The presence of PNI in
      biopsies with GS 3 + 4 = 7 PCa is associated with upstaging at RP but is a weaker
      predictor of >=pT3 disease than cribriform morphology.

PMID- 27709738
TI  - Wnt-beta-catenin signaling regulates ABCC3 (MRP3) transporter expression in
      colorectal cancer.
AB  - We determined the gene expression profiles for 48 ATP binding cassette (ABC)
      transporters in matched colon cancer and normal colon tissues in order to provide
      insight into the mechanisms underlying expression of transporters related to
      colon carcinogenesis. The expression of ABCB1, ABCC1, ABCC2, ABCC3, and ABCG2 was
      altered in association with colon carcinogenesis. Among these transporters, the
      expression of ABCC3 was repressed by Wnt signaling pathway in colon cancer cell
      lines. Knockdown of the pathway components transcription factor 7-like 2 (TCF7L2)
      or beta-catenin thus increased ABCC3 expression, whereas activation of Wnt
      signaling with inhibitors of glycogen synthase kinase-3beta (GSK-3beta) reduced
      it. ChIP and luciferase reporter assays also showed that TCF7L2 binds to the
      ABCC3 locus and regulates its expression. Finally, overexpression of ABCC3 in
      colon cancer cells conferred resistance to anticancer drug-induced cytotoxicity.
      Our data thus suggest that Wnt signaling represses ABCC3 expression during colon
      carcinogenesis, and that subsequent upregulation of ABCC3 expression during drug
      treatment might contribute to acquired drug resistance.

PMID- 27709740
TI  - Effects of organic loading rate on hydrogen and volatile fatty acid production
      and microbial community during acidogenic hydrogenesis in a continuous stirred
      tank reactor using molasses wastewater.
AB  - AIMS: Microbial community associated with hydrogen production and volatile fatty
      acids (VFAs) accumulation was characterized in acidogenic hydrogenesis using
      molasses wastewater as a feedstock. METHODS AND RESULTS: Hydrogen and VFAs
      production were measured under an organic loading rate (OLR) from 19 to 35 g-COD
      l-1  day-1 . The active microbial community was analysed using RNA-based
      massively parallel sequencing technique, and their correlation patterns were
      analysed using networking analysis. The continuous stirred tank reactor achieved
      stable hydrogen production at different OLR conditions, and the maximum hydrogen
      production rate (HPR) was 1.02 L-H2  l-1  day-1 at 31.0 g-COD l-1  day-1 .
      Butyrate (50%) and acetate (38%) positively increased with increase in OLR. Total
      VFA production stayed around 7135 mg l-1 during the operation period. Although
      Clostridiales and Lactobacillales were relatively abundant, the HPR was
      positively associated with Pseudomonadaceae and Micrococcineae. Total VFA and
      acetate, butyrate and propionate concentrations were positively correlated with
      lactic acid bacteria (LAB) such as Bacillales, Sporolactobacillus and
      Lactobacillus. CONCLUSIONS: The close relationship between Pseudomonadaceae and
      Micrococcineae, and LAB play important roles for stable hydrogen and VFA
      production from molasses wastewater. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Microbial information on hydrogen and VFA production can be useful to design and
      operate for acidogenic hydrogenesis using high strength molasses wastewater.

PMID- 27709741
TI  - Advancing knowledge about dating violence.

PMID- 27709742
TI  - Effects of child abuse, adolescent violence, peer approval and pro-violence
      attitudes on intimate partner violence in adulthood.
AB  - BACKGROUND: Children's exposure to violence increases their risk for later
      victimisation and perpetration of intimate partner violence (IPV). However, the
      relative influence of child abuse, adolescent violence, peer approval of violence
      and pro-violence attitudes on later IPV is not well established. AIMS: Analyses
      focus on the prediction of adult IPV from variables measured in childhood and
      adolescence to establish the unique influence of earlier victimisation and
      perpetration of violence, as well as other variables grounded in theory and
      empirical findings. METHODS: Data are from a longitudinal study that began in the
      1970s with a sample of 457 preschool-aged children who were reassessed as adults.
      Outcomes of adult IPV victimisation and perpetration types were regressed on
      predictors of parent-reported child abuse, officially recorded child
      maltreatment, adolescent victimisation, violence perpetration, pro-violence
      attitudes and peer approval of violence during adolescence, controlling for
      childhood Socio Economic Status (SES), age in adolescence and gender. RESULTS:
      Dating violence victimisation and peer approval of dating violence in adolescence
      emerged as the unique predictors of IPV victimisation and perpetration in
      adulthood. Official child maltreatment predicted IPV perpetration. CONCLUSIONS:
      Results underscore the importance of prevention programmes and strategies to
      disrupt the cycle of violence at its early stages, as well as interventions
      during adolescence targeting peer influences. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27709743
TI  - Risk assessments for dating violence in mid to late adolescence and early
      adulthood.
AB  - AIM: The objective of this paper is to review risk instruments that have been
      used in the assessment of the potential for violence within the dating
      relationships of young people. METHOD: A review of the dating violence literature
      was conducted to identify risk assessment approaches that have been used to
      predict harmful behaviour within the dating relationships of people aged between
      15 and 30 years. Risk assessments were evaluated on recommended quality criteria:
      predictive validity, accuracy (sensitivity and specificity) and inter-rater
      reliability. RESULTS: Only five studies describing assessments that focused
      specifically on dating violence risk factors were selected for review. Three
      assessments encompassed dating behaviours by victims that have been associated
      with an increased risk of further victimisation. CONCLUSIONS: Drawing on this
      evidence, we conclude that young people appear to be at greater risk of
      encountering dating violence if they have experienced violence in earlier
      attachment relationships; if their skills for coping with conflict and responding
      to coercion are limited and if the presence of peer influences reinforces offence
      supportive attitudes. The reliability and validity of existing intimate partner
      violence risk assessments that conceptually overlap with elements of dating
      violence risk warrant investigation to inform risk assessment developments in
      this field and, building on this, possible interventions to minimise future harm.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27709744
TI  - Risk factors for dating violence versus cohabiting violence: Results from the
      third generation of the Cambridge Study in Delinquent Development.
AB  - BACKGROUND: Dating violence is an important problem. Evidence suggests that women
      are more likely to perpetrate dating violence. AIMS: The present study
      investigates the prevalence of dating violence compared with cohabiting violence
      in a community sample of men and women and assesses to what extent child and
      adolescent explanatory factors predict this behaviour. A secondary aim is to
      construct a risk score for dating violence based on the strongest risk factors.
      METHODS: The Cambridge Study in Delinquent Development is a prospective
      longitudinal survey of 411 men (generation 2) born in the 1950s in an inner
      London area. Most recently, their sons and daughters [generation 3 (G3)] have
      been interviewed regarding their perpetration of dating and cohabiting violence,
      utilising the Conflict Tactics Scale. Risk factors were measured in four domains
      (family, parental, socio-economic and individual). RESULTS: A larger proportion
      of women than men perpetrated at least one act of violence towards their dating
      partner (36.4 vs 21.7%). There was a similar pattern for cohabiting violence
      (39.6 vs 21.4%). A number of risk factors were significantly associated with the
      perpetration of dating violence. For G3 women, these included a convicted father,
      parental conflict, large family size and poor housing. For G3 men, these included
      having a young father or mother, separation from the father before age 16, early
      school leaving, frequent truancy and having a criminal conviction. A risk score
      for both men and women, based on 10 risk factors, significantly predicted dating
      violence. CONCLUSION: Risk factors from four domains were important in predicting
      dating violence, but they were different for G3 men and women. It may be
      important to consider different risk factors and different risk assessments for
      male compared with female perpetration of dating violence. Early identification
      and interventions are recommended. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27709745
TI  - From early dating violence to adult intimate partner violence: Continuity and
      sources of resilience in adulthood.
AB  - BACKGROUND: Previous literature has found continuity for intimate partner
      violence, but little research has explored continuity between dating violence and
      adult intimate partner violence (IPV) or whether protective factors may attenuate
      this relationship. AIMS: This research hypothesised a positive relationship
      between dating violence in early adulthood and later adulthood IPV and that
      support and attachment would provide buffering and direct protection for this
      relationship. METHODS: Data from the Rochester Youth Development Study were used
      to explore these questions through negative binomial regression. RESULTS: Dating
      violence was statistically significantly related to an increase of adult IPV.
      Family support, parental reports of attachment to the subject, peer support and
      parenting-related social support all were protective factors that provided a
      direct effect for those respondents perpetrating dating violence. None of the
      protective factors provided buffering protection between dating violence and
      adult IPV. CONCLUSIONS: Results confirm significant continuity between dating
      violence and IPV and that support from peers and family, parenting-related
      support and parental reports of attachment protect an individual from continuing
      to engage in intimate partner violence throughout adulthood. Bolstering these
      supportive relationships may help provide points of intervention to interrupt the
      link between early dating violence and later adulthood IPV. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27709747
TI  - Dating violence in teenage girls: parental emotion regulation and racial
      differences.
AB  - BACKGROUND: Teen dating violence (TDV) is a common phenomenon of great public
      concern. TDV may lead to severe long-term consequences for victims and offenders,
      and even more so for females than for males. AIM: The aim of this paper is to
      investigate possible underlying factors for involvement in TDV either as a
      perpetrator or a victim. Social learning theory is commonly used to explain
      internalisation of parents' behaviour on children's behavioural expressions, but
      less so on parents' emotion regulation as a direct link to later TDV. METHOD: We
      used longitudinal data from the Pittsburgh Girls Study (N = 2450) to investigate
      if and how parents' positive and negative emotion regulation is related to TDV,
      controlling for early aggression and race. RESULTS: Results show a moderately
      strong association between parents' negative emotion regulation and their
      daughters' involvement in serious dating violence. We also found that many more
      African American girls were involved in TDV compared to Caucasian girls, both as
      a perpetrator and victim. CONCLUSIONS AND PRACTICAL IMPLICATIONS: We discuss
      directions for future research focusing on emotion regulation and dating
      violence. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27709746
TI  - Dating violence and physical health: A longitudinal lens on the significance of
      relationship dynamics and anti-social lifestyle characteristics.
AB  - BACKGROUND: Scholars have documented the significant physical health consequences
      of intimate partner violence. Yet, because existing research draws primarily on
      clinical samples of adult women, it is unclear whether exposure to dating
      violence is related to health detriments among young men and women. Furthermore,
      data limitations largely have precluded consideration of the mechanisms
      underlying these previously observed associations. AIMS: We sought to examine the
      direct association between dating violence and self-rated physical health during
      adolescence and across the transition to adulthood. We also directed attention to
      potential mediating and confounding factors, including negative relationship
      dynamics, anti-social lifestyle characteristics and physical health correlates.
      METHODS: Drawing on five waves of data from the Toledo Adolescent Relationships
      Study (n = 3746 person-periods), we used growth curve analyses to examine these
      associations among a sample of young men and women in dating relationships.
      RESULTS: Longitudinal analyses revealed that dating violence was associated with
      declines in self-rated physical health across the period from adolescence to
      young adulthood. This effect, however, was attenuated with the inclusion of
      negative relationship dynamics. CONCLUSIONS: Findings suggest the need to further
      examine the physical health consequences of dating violence, with a particular
      focus on the relationship context and other potential confounding forces.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27709748
TI  - Predictors of emotional and physical dating violence in a sample of serious
      juvenile offenders.
AB  - AIM: We estimate group-based dating violence trajectories and identify the
      adolescent risk factors that explain membership in each trajectory group. METHOD:
      Using longitudinal data from the Pathways to Desistance Study, which follows a
      sample of 1354 serious juvenile offenders from Philadelphia, Pennsylvania and
      Phoenix, Arizona between mid-adolescence and early adulthood, we estimate group
      based trajectory models of both emotional dating violence and physical dating
      violence over a span of five years in young adulthood. We then estimate
      multinomial logistic regression models to identify theoretically motivated risk
      factors that predict membership in these groups. RESULTS: We identified three
      developmental patterns of emotional dating violence: none (33%), low-level (59%)
      and high-level decreasing (8%). The best-fitting model for physical dating
      violence also had three groups: none (73%), low-level (24%) and high-level (3%).
      Race/ethnicity, family and psychosocial variables were among the strongest
      predictors of both emotional and physical dating violence. In addition,
      delinquency history variables predicted emotional dating violence and
      relationship variables predicted physical dating violence. CONCLUSIONS: Dating
      violence is quite prevalent in young adulthood among serious juvenile offenders.
      Numerous predictors distinguish between chronic dating violence perpetrators and
      other groups. These may suggest points of intervention for reducing future
      violence. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27709749
TI  - Visible Light Activation of Boronic Esters Enables Efficient Photoredox C(sp2 )
      C(sp3 ) Cross-Couplings in Flow.
AB  - We report herein a new method for the photoredox activation of boronic esters.
      Using these reagents, an efficient and high-throughput continuous flow process
      was developed to perform a dual iridium- and nickel-catalyzed C(sp2 )-C(sp3 )
      coupling by circumventing solubility issues associated with potassium
      trifluoroborate salts. Formation of an adduct with a pyridine-derived Lewis base
      was found to be essential for the photoredox activation of the boronic esters.
      Based on these results we were able to develop a further simplified visible light
      mediated C(sp2 )-C(sp3 ) coupling method using boronic esters and cyano
      heteroarenes under flow conditions.

PMID- 27709750
TI  - Concomitant implantation of Impella(r) on top of veno-arterial extracorporeal
      membrane oxygenation may improve survival of patients with cardiogenic shock.
AB  - AIMS: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support
      stabilizes patients with cardiogenic shock. Despite improved oxygenation and
      peripheral circulation, LV unloading may be impeded due to the increased
      afterload, resulting in a failing static left ventricle and in high mortality.
      METHODS AND RESULTS: We describe for the first time a large series of patients
      treated with the combination of VA-ECMO and Impella(r) compared with patients
      with VA-ECMO only. We retrospectively collected data on patients from two
      tertiary critical care referral centres. We enrolled 157 patients treated with VA
      ECMO from January 2013 to April 2015: 123 received VA-ECMO support and 34 had
      concomitant treatment with VA-ECMO and Impella. A propensity-matching analysis
      was performed in a 2:1 ratio, resulting in 42 patients undergoing VA-ECMO alone
      (control group) compared with 21 patients treated with VA-ECMO and Impella.
      Patients in the VA-ECMO and Impella group had a significantly lower hospital
      mortality (47% vs. 80%, P < 0.001) and a higher rate of successful bridging to
      either recovery or further therapy (68% vs. 28%, P < 0.001) compared with VA-ECMO
      patients. A higher need for continuous veno-venous haemofiltration (48% vs. 19%,
      P = 0.02) and increased haemolysis (76% vs. 33%, P = 0.004) were reported in the
      study group due to higher survival. There was no difference in major bleeding
      rates between the two groups (VA-ECMO and Impella 38% vs. VA-ECMO 29%, P = 0.6).
      CONCLUSIONS: Concomitant treatment with VA-ECMO and Impella may improve outcome
      in patients with cardiogenic shock compared with VA-ECMO only. Nevertheless,
      randomized studies are needed to validate these promising results further.

PMID- 27709751
TI  - Amyloid beta-induced astrogliosis is mediated by beta1-integrin via NADPH oxidase
      2 in Alzheimer's disease.
AB  - Astrogliosis is a hallmark of Alzheimer's disease (AD) and may constitute a
      primary pathogenic component of that disorder. Elucidation of signaling cascades
      inducing astrogliosis should help characterizing the function of astrocytes and
      identifying novel molecular targets to modulate AD progression. Here, we describe
      a novel mechanism by which soluble amyloid-beta modulates beta1-integrin activity
      and triggers NADPH oxidase (NOX)-dependent astrogliosis in vitro and in vivo.
      Amyloid-beta oligomers activate a PI3K/classical PKC/Rac1/NOX pathway which is
      initiated by beta1-integrin in cultured astrocytes. This mechanism promotes beta1
      integrin maturation, upregulation of NOX2 and of the glial fibrillary acidic
      protein (GFAP) in astrocytes in vitro and in hippocampal astrocytes in vivo.
      Notably, immunochemical analysis of the hippocampi of a triple-transgenic AD
      mouse model shows increased levels of GFAP, NOX2, and beta1-integrin in reactive
      astrocytes which correlates with the amyloid beta-oligomer load. Finally,
      analysis of these proteins in postmortem frontal cortex from different stages of
      AD (II to V/VI) and matched controls confirmed elevated expression of NOX2 and
      beta1-integrin in that cortical region and specifically in reactive astrocytes,
      which was most prominent at advanced AD stages. Importantly, protein levels of
      NOX2 and beta1-integrin were significantly associated with increased amyloid-beta
      load in human samples. These data strongly suggest that astrogliosis in AD is
      caused by direct interaction of amyloid beta oligomers with beta1-integrin which
      in turn leads to enhancing beta1-integrin and NOX2 activity via NOX-dependent
      mechanisms. These observations may be relevant to AD pathophysiology.

PMID- 27709752
TI  - Background factors associated with problem avoidance behavior in healthy partners
      of breast cancer patients.
AB  - OBJECTIVE: We evaluated avoidance behaviors of healthy partners of breast cancer
      patients and sought to (1) describe men's perception of their own avoidance
      behavior and (2) identify the background factors associated with such behavior.
      METHODS: An Internet-based survey was conducted, and analysis was performed on
      the responses of 368 male spouses of female breast cancer patients. RESULTS:
      Thirty to forty percent of spouses had some type of problem avoidance behavior
      toward their wives. There was a high correlation (r = 0.70, P < .001) between
      problem avoidance behavior at the time of diagnosis and subsequent problem
      behavior (mean follow-up period after diagnosis: 1.3 + 1.1 years). The
      characteristics of spouses with avoidant behaviors included having wives with
      recurrence, having wives treated with anticancer drug therapy or total resection,
      and having their own experience of cancer. Covariance structure analysis revealed
      2 factors related to the background of spouses with problem avoidance behavior:
      (1) having a sense of difficulty in coping (beta = 0.68, P < .001) and (2) having
      a poor marital relationship (beta = -0.27, P < .001). CONCLUSIONS: Our findings
      suggest that problem avoidance behavior among healthy male partners of breast
      cancer patients is common and correlates with difficulty coping and a poor
      marital relationship. It is important to address both the problem avoidance
      behavior itself and to support couples early, before this behavior surfaces.

PMID- 27709753
TI  - Monitoring ssDNA Binding to the DnaB Helicase from Helicobacter pylori by Solid
      State NMR Spectroscopy.
AB  - DnaB helicases are bacterial, ATP-driven enzymes that unwind double-stranded DNA
      during DNA replication. Herein, we study the sequential binding of the "non
      hydrolysable" ATP analogue AMP-PNP and of single-stranded (ss) DNA to the
      dodecameric DnaB helicase from Helicobacter pylori using solid-state NMR.
      Phosphorus cross-polarization experiments monitor the binding of AMP-PNP and DNA
      to the helicase. 13 C chemical-shift perturbations (CSPs) are used to detect
      conformational changes in the protein upon binding. The helicase switches upon
      AMP-PNP addition into a conformation apt for ssDNA binding, and AMP-PNP is
      hydrolyzed and released upon binding of ssDNA. Our study sheds light on the
      conformational changes which are triggered by the interaction with AMP-PNP and
      are needed for ssDNA binding of H. pylori DnaB in vitro. They also demonstrate
      the level of detail solid-state NMR can provide for the characterization of
      protein-DNA interactions and the interplay with ATP or its analogues.

PMID- 27709754
TI  - Imidazole-Aided Native Chemical Ligation: Imidazole as a One-Pot Desulfurization
      Amenable Non-Thiol-Type Alternative to 4-Mercaptophenylacetic Acid.
AB  - Various bioactive proteins have been synthesized by native chemical ligation
      (NCL) and its combination with subsequent desulfurization (e.g., conversion from
      Cys to Ala). In NCL, excess 4-mercaptophenylacetic acid (MPAA) is generally added
      to facilitate the reaction. However, co-elution of MPAA with the ligation product
      during preparative high-performance liquid chromatography sometimes reduces its
      usefulness. In addition, contamination of MPAA disturbs subsequent
      desulfurization. Here, we report for the first time that imidazole can be adopted
      as an alternative to MPAA in NCL using a peptide-alkylthioester. The efficiency
      of the imidazole-aided NCL (Im-NCL) is similar to that of traditional MPAA-aided
      NCL. As model cases, we successfully synthesized adiponectin(19-107) and [Ser(PO3
      H2 )65 ]-ubiquitin using Im-NCL with a one-pot desulfurization.

PMID- 27709755
TI  - Microbial eukaryote communities exhibit robust biogeographical patterns along a
      gradient of Patagonian and Antarctic lakes.
AB  - Microbial eukaryotes play important roles in aquatic ecosystem functioning.
      Unravelling their distribution patterns and biogeography provides important
      baseline information to infer the underlying mechanisms that regulate the
      biodiversity and complexity of ecosystems. We studied the distribution patterns
      and factors driving diversity gradients in microeukaryote communities (total,
      abundant, uncommon and rare community composition) along a latitudinal gradient
      of lakes distributed from Argentinean Patagonia to Maritime Antarctica using both
      denaturing gradient gel electrophoresis (DGGE) and high-throughput sequencing
      (Illumina HiSeq). DGGE and abundant Illumina operational taxonomic units (OTUs)
      showed both decreasing richness with latitude and significant differences between
      Patagonian and Antarctic lakes communities. In contrast, total richness did not
      change significantly across the latitudinal gradient, although evenness and
      diversity indices were significantly higher in Patagonian lakes. Beta-diversity
      was characterized by a high species turnover, influenced by both environmental
      and geographical descriptors, although this pattern faded in the rare community.
      Our results suggest the co-existence of a 'core biosphere' containing reduced
      number of abundant/dominant OTUs on which classical ecological rules apply,
      together with a much larger seedbank of rare OTUs driven by stochastic and
      reduced dispersal processes. These findings shed new light on the biogeographical
      patterns and forces structuring inland microeukaryote composition across broad
      spatial scales.

PMID- 27709756
TI  - Structural Basis for Phospholyase Activity of a Class III Transaminase Homologue.
AB  - Pyridoxal-phosphate (PLP)-dependent enzymes catalyse a remarkable diversity of
      chemical reactions in nature. A1RDF1 from Arthrobacter aurescens TC1 is a fold
      type I, PLP-dependent enzyme in the class III transaminase (TA) subgroup. Despite
      sharing 28 % sequence identity with its closest structural homologues, including
      beta-alanine:pyruvate and gamma-aminobutyrate:alpha-ketoglutarate TAs, A1RDF1
      displayed no TA activity. Activity screening revealed that the enzyme possesses
      phospholyase (E.C. 4.2.3.2) activity towards O-phosphoethanolamine (PEtN), an
      activity described previously for vertebrate enzymes such as human AGXT2L1,
      enzymes for which no structure has yet been reported. In order to shed light on
      the distinctive features of PLP-dependent phospholyases, structures of A1RDF1 in
      complex with PLP (internal aldimine) and PLP?PEtN (external aldimine) were
      determined, revealing the basis of substrate binding and the structural factors
      that distinguish the enzyme from class III homologues that display TA activity.

PMID- 27709758
TI  - Atom-Efficient Synthesis of Alkynylfluoroborates Using BF3 -Based Frustrated
      Lewis Pairs.
AB  - A sterically demanding amine, 1,2,2,6,6-pentamethylpiperidine (PMP), forms a
      highly reactive Lewis acid-base pair with boron trifluoride. This pair reacts
      with terminal acetylenes to give the products of C(sp)-H borylation, previously
      unknown tri- and tetraalkynylboron compounds. Trialkynylfluoroborates can serve
      as surrogates of alkynyltrifluoroborates for C-C coupling reactions. Using
      aqueous NaOH, PMP can be recovered from its tetrafluoroborate salt, which is
      formed as a C-H borylation byproduct. Combining the discovered borylation
      reactivity with the PMP recovery provides a straightforward and atom-efficient
      approach to synthetically useful alkynylfluoroborates.

PMID- 27709759
TI  - Mesoporous Amorphous Silicon: A Simple Synthesis of a High-Rate and Long-Life
      Anode Material for Lithium-Ion Batteries.
AB  - Amorphous Si (a-Si) shows potential advantages over crystalline Si (c-Si) in
      lithium-ion batteries, owing to its high lithiation potential and good tolerance
      to intrinsic strain/stress. Herein, porous a-Si has been synthesized by a simple
      process, without the uses of dangerous or expensive reagents, sophisticated
      equipment, and strong acids that potential cause environment risks. These porous
      a-Si particles exhibit excellent electrochemical performances, owing to their
      porous structure, amorphous nature, and surface modification. They deliver a
      capacity of 1025 mAh g-1 at 3 A g-1 after 700 cycles. Moreover, the reversible
      capacity after electrochemical activation, is quite stable throughout the
      cycling, resulting in a capacity retention about around 88 %. The direct
      comparison between a-Si and c-Si anodes clearly supports the advantages of a-Si
      in lithium-ion batteries.

PMID- 27709757
TI  - Increased basal ganglia binding of 18 F-AV-1451 in patients with progressive
      supranuclear palsy.
AB  - BACKGROUND: Progressive supranuclear palsy (PSP) is difficult to diagnose
      accurately. The recently developed tau PET tracers may improve the diagnostic
      work-up of PSP. METHODS: Regional tau accumulation was studied using 18 F-AV-1451
      PET in 11 patients with PSP and 11 age-matched healthy controls in the Swedish
      BioFinder study. RESULTS: 18 F-AV-1451 standard uptake volume ratios were
      significantly higher in the basal ganglia in PSP patients when compared with
      controls (globus pallidus 1.75 vs 1.50; putamen 1.51 vs 1.35). Retention in the
      basal ganglia was correlated with age in both groups (r = .43-.78, P < .05). In
      PSP, we observed a significant correlation between clinical deterioration
      measured with the PSP rating scale and standard uptake volume ratios in the
      globus pallidus (r = .74, P < .05). However, no 18 F-AV-1451 retention was
      observed in the cerebral cortex or white matter of either PSP patients or
      controls, and autoradiography did not reveal any specific binding of AV-1451 to
      PSP tau aggregates. CONCLUSION: We found higher 18 F-AV-1451 retention in the
      basal ganglia of PSP patients when compared with healthy elderly controls, but
      also increases with age in both controls and patients. As a result of the overlap
      in retention between diagnostic groups and the age-dependent increase present
      also in controls, 18 F-AV-1451 PET might not reliably distinguish individual
      patients with PSP from controls. However, further studies are needed to evaluate
      whether 18 F-AV-1451 PET might be useful as a progression marker in clinical PSP
      trials. (c) The Authors. Movement Disorders published by Wiley Periodicals, Inc.
      on behalf of International Parkinson and Movement Disorder Society.

PMID- 27709760
TI  - Photoisomerization of Arylazopyrazole Photoswitches: Stereospecific Excited-State
      Relaxation.
AB  - Electronic structure calculations and nonadiabatic dynamics simulations (more
      than 2000 trajectories) are used to explore the Z-E photoisomerization mechanism
      and excited-state decay dynamics of two arylazopyrazole photoswitches. Two chiral
      S1 /S0 conical intersections with associated enantiomeric S1 relaxation paths
      that are barrierless and efficient (timescale of ca. 50 fs) were found. For the
      parent arylazopyrazole (Z8) both paths contribute evenly to the S1 excited-state
      decay, whereas for the dimethyl derivative (Z11) each of the two chiral cis
      minima decays almost exclusively through one specific enantiomeric S1 relaxation
      path. To our knowledge, the Z11 arylazopyrazole is thus the first example for
      nearly stereospecific unidirectional excited-state relaxation.

PMID- 27709761
TI  - Reaction of Pentelidene Complexes with Diazoalkanes: Stabilization of Parent 2,3
      Dipnictabutadienes.
AB  - The reaction of the phosphinidene complex [Cp*P{W(CO)5 }2 ] (1 a) with
      diphenyldiazomethane leads to [{W(CO)5 }Cp*P=NN{W(CO)5 }=CPh2 ] (2). Compound 2
      is a rare example of a phosphadiazadiene ligand (R-P=N-N=CR'R'') complex. At
      temperatures above 0  degrees C, 2 decomposes into the complex [{W(CO)5
      }PCp*{N(H)N=CPh2 )2 ] (3), among other species. The reaction of the pentelidene
      complexes [Cp*E{W(CO)5 }2 ] (E=P, As) with diazomethane (CH2 NN) proceeds
      differently. For the arsinidene complex (1 b), only the arsaalkene complex 4 b
      [{W(CO)5 }2 {eta1:2 -(Cp*)As=CH2 }] is formed. The reaction with the
      phosphinidene complex (1 a) results in three products, the two phosphaalkene
      complexes [{W(CO)5 }2 {eta1:2 -(R)P=CH2 }] (4 a: R=Cp*, 5: R=H) and the
      triazaphosphole derivative [{W(CO)5 }P(Cp*)-CH2 -N{W(CO)5 }=N-N(N=CH2 )] (6 a).
      The phosphaalkene complex (4 a) and the arsaalkene complex (4 b) are not stable
      at room temperature and decompose to the complexes [{W(CO)5 }4 (CH2 =E-E=CH2 )]
      (7 a: E=P, 7 b: E=As), which are the first examples of complexes with parent 2,3
      diphospha-1,3-butadiene and 2,3-diarsa-1,3-butadiene ligands.

PMID- 27709762
TI  - Pharmacological properties of faster-acting insulin aspart vs insulin aspart in
      patients with type 1 diabetes receiving continuous subcutaneous insulin infusion:
      A randomized, double-blind, crossover trial.
AB  - AIM: To evaluate the pharmacological characteristics of faster-acting insulin
      aspart (faster aspart) compared with insulin aspart (IAsp) during continuous
      subcutaneous insulin infusion (CSII). METHODS: In this randomized, double-blind,
      crossover trial, 48 men and women aged 18 to 64 years with type 1 diabetes
      mellitus (T1DM) received faster aspart and IAsp as a 0.15 U/kg bolus dose via
      CSII, on top of a basal rate (0.02 U/kg/h), in a glucose clamp setting (target
      5.5 mmol/L). RESULTS: After a CSII bolus dose, the
      pharmacokinetic/pharmacodynamic profiles for faster aspart were left-shifted
      compared with those for IAsp. For faster aspart vs IAsp, the early glucose
      lowering effect (area under the curve for glucose infusion rate [GIR]0-30min )
      was approximately 2-fold higher (least squares means 24.9 vs 11.4 mg/kg;
      estimated ratio faster aspart/IAsp 2.18, 95% confidence interval [CI] [1.33;
      5.04]; P = .002), onset of glucose-lowering effect (time to early 50% of maximum
      GIR) occurred 11.1 minutes earlier (41.1 vs 52.3 minutes; 95% CI faster aspart -
      IAsp [-15.4; -6.9]; P<.001), and offset of glucose-lowering effect (time to late
      50% of maximum GIR) occurred 24.0 minutes earlier (214.7 vs 238.7 minutes; 95% CI
      [-38.9; -9.1]; P=.002). Likewise, significantly greater early exposure and
      significantly earlier onset and offset of exposure were observed for faster
      aspart vs IAsp. Faster aspart and IAsp were both well tolerated. CONCLUSIONS: In
      patients with T1DM using CSII, faster aspart better mimics the endogenous
      prandial insulin secretion and action than does IAsp. Faster aspart therefore has
      the potential to provide clinical benefits over current rapid-acting insulins in
      the insulin pump setting.

PMID- 27709763
TI  - C(sp3 )-H Oxidative Addition and Transfer Hydrogenation Chemistry of a
      Titanium(II) Synthon: Mimicry of Late-Metal Type Reactivity.
AB  - Two-electron reduction of the TiIV compound (ket guan)(ImDipp N)Ti(OTf)2 (3)
      gives the arene-masked complex (ket guan)(eta6 -ImDipp N)Ti (1) in excellent
      yield. Upon standing in solution, 1 converts to a TiIV metallacycle (4) through
      dehydrogenation of a pendant isopropyl group. Spectroscopic evidence shows this
      transformation initially proceeds via the oxidative addition of a C(sp3 )-H bond
      and can be reversed upon exposure of 4 to H2 . Interestingly, treatment of 1 with
      cyclohexene gives cyclohexane and 4 via a titanium-mediated transfer
      hydrogenation reaction, a process that can be extended to catalytically
      hydrogenate other unsaturated hydrocarbons under mild conditions. These results,
      rare for the early-metals, suggest 1 possesses chemical characteristics
      reminiscent of noble, late-metals.

PMID- 27709764
TI  - A Novel Pseudo-Protein-Based Biodegradable Nanomicellar Platform for the Delivery
      of Anticancer Drugs.
AB  - Amino acid-based poly(ester amide)s are a new family of biodegradable polymers
      that exhibit "pseudo-protein" characteristics and the structural varieties of
      poly(ester amide)s make them hold great potential in multiple biomedical
      applications. In this study, a lysine-phenylalanine-based pseudo-protein is
      developed as the self-assembled nanomicellar carrier for efficient delivery of
      doxorubicin. The lysine moieties from the pseudo-protein provide available sites
      for further functionalization, and methylcoumarin is introduced for easy and
      photocontrollable crosslinking, to effectively improve the micellar stability in
      serum containing environment and against dilution. However, photocrosslinks do
      not bring in any barrier for the intracellular release of doxoubicin. Doxorubicin
      release is significantly accelerated by proteolytic enzyme, due to the
      biodegradability of pseudo-protein micelles. In addition, pseudo-protein delivery
      system exhibits unique interactions with HCT116 human colon cancer cells.
      Doxorubicin loaded in pseudo-protein micelles colocalizes with mitochondria and
      endolysosomes, while free doxorubicin is distributed only in the nuclei.
      Doxorubicin-loaded pseudo-protein micelles stimulate increased level of
      intracellular reactive oxygen species and mitochondrial damage. Free doxorubicin
      induces conditional apoptosis in HCT116 cells between 0.5* 10-6 and 2 * 10-6 m,
      while DOX loaded in pseudo-protein micelles induces apoptosis over a
      higher/broader concentration range (2 * 10-6 -10 * 10-6 m).

PMID- 27709765
TI  - A Ruthenium(III)-Oxyl Complex Bearing Strong Radical Character.
AB  - Proton-coupled electron-transfer oxidation of a RuII -OH2 complex, having an N
      heterocyclic carbene ligand, gives a RuIII -O. species, which has an
      electronically equivalent structure of the RuIV =O species, in an acidic aqueous
      solution. The RuIII -O. complex was characterized by spectroscopic methods and
      DFT calculations. The oxidation state of the Ru center was shown to be close to
      +3; the Ru-O bond showed a lower-energy Raman scattering at 732 cm-1 and the Ru-O
      bond length was estimated to be 1.77(1) A. The RuIII -O. complex exhibits high
      reactivity in substrate oxidation under catalytic conditions; particularly,
      benzaldehyde and the derivatives are oxidized to the corresponding benzoic acid
      through C-H abstraction from the formyl group by the RuIII -O. complex bearing a
      strong radical character as the active species.

PMID- 27709767
TI  - Reversible Dihydrogen Activation by Reduced Aryl Boranes as Main-Group
      Ambiphiles.
AB  - A new approach to main-group H2 activation combining concepts of transition-metal
      and frustrated Lewis pair chemistry is reported. Ambiphilic, metal-like
      reactivity toward H2 can be conferred to 9,10-dihydro-9,10-diboraanthracene (DBA)
      acceptors by the injection of two electrons. The resulting [DBA]2- ions cleave
      the H-H bond with the formation of hydridoborates under moderate conditions (T=50
      100  degrees C; p<1 atm). Depending on the boron-bonded substituents R, the
      addition is either reversible (R=C=CtBu) or irreversible (R=H). The reaction rate
      is strongly influenced by the nature and the coordination behavior of the
      countercation (Li+ slower than K+ ). Quantum-chemical calculations support the
      experimental observations and suggest a concerted, homolytic addition of H2
      across both boron atoms. As proven by the successful conversion of Me3 SiCl into
      Me3 SiH, the system Li2 [DBA]/H2 appears generally relevant for the hydrogenation
      of element-halide bonds.

PMID- 27709766
TI  - Site-Specific Immobilization of the Peptidoglycan Synthase PBP1B on a Surface
      Plasmon Resonance Chip Surface.
AB  - Surface plasmon resonance (SPR) is one of the most powerful label-free methods to
      determine the kinetic parameters of molecular interactions in real time and in a
      highly sensitive way. Penicillin-binding proteins (PBPs) are peptidoglycan
      synthesis enzymes present in most bacteria. Established protocols to analyze
      interactions of PBPs by SPR involve immobilization to an ampicillin-coated chip
      surface (a beta-lactam antibiotic mimicking its substrate), thereby forming a
      covalent complex with the PBPs transpeptidase (TP) active site. However, PBP
      interactions measured with a substrate-bound TP domain potentially affect
      interactions near the TPase active site. Furthermore, in vivo PBPs are anchored
      in the inner membrane by an N-terminal transmembrane helix, and hence
      immobilization at the C-terminal TPase domain gives an orientation contrary to
      the in vivo situation. We designed a new procedure: immobilization of PBP by
      copper-free click chemistry at an azide incorporated in the N terminus. In a
      proof-of-principle study, we immobilized Escherichia coli PBP1B on an SPR chip
      surface and used this for the analysis of the well-characterized interaction of
      PBP1B with LpoB. The site-specific incorporation of the azide affords control
      over protein orientation, thereby resulting in a homogeneous immobilization on
      the chip surface. This method can be used to study topology-dependent
      interactions of any (membrane) protein.

PMID- 27709768
TI  - Oxidized g-C3 N4 Nanospheres as Catalytically Photoactive Linkers in MOF/g-C3 N4
      Composite of Hierarchical Pore Structure.
AB  - A unique composite of the copper-based metal-organic framework (Cu-benzene
      tricarboxylic acid (BTC)) with oxidized graphitic carbon nitride nanospheres is
      synthesized. For comparison, a hybrid material consisting of g-C3 N4 and Cu-BTC
      is also obtained. Their surface features are analyzed using Fourier transform
      infrared spectroscopy, X-ray diffraction, sorption of nitrogen, thermal analysis,
      scanning electron microscopy, photoluminescence, and diffuse reflectance UV-Vis
      spectroscopy. The results suggest that the formed nanospheres of oxidized g-C3 N4
      act as linkers between the copper sites, playing a crucial role in the composite
      building process. Their incorporation to the Cu-BTC framework causes the
      development of new mesoporosity. Remarkable alterations in the optical
      properties, as a result of the coordination of oxygen containing functional
      groups of the oxidized graphitic carbon nitride to the copper atoms of the
      framework, suggest an increase in photoreactivity. On the other hand, for the
      hybrid material consisting of Cu-BTC and g-C3 N4 , the unaltered pore volume and
      optical properties support the formation of a physical mixture rather than of a
      composite. The tests on reactive adsorption and detoxification of G-series
      organophosphate nerve agent surrogate show the enhanced performance of the
      composite as catalysts and photocatalyst in visible light.

PMID- 27709769
TI  - Manipulation of Amorphous-to-Crystalline Transformation: Towards the Construction
      of Covalent Organic Framework Hybrid Microspheres with NIR Photothermal
      Conversion Ability.
AB  - An approach to transforming amorphous organic networks into crystalline covalent
      organic frameworks (COFs) with retention of the colloidal nanosize and uniform
      morphology is presented. Specifically, Fe3 O4 nanoclusters are encapsulated by a
      disordering polyimine network via the Schiff-base reaction. The formed imine
      bonds could be reconstructed under thermodynamic control to reform the polyimine
      networks into imine-linked COFs in situ. Such a core-shell microsphere exhibits
      the uniform size and spherical shape, controllable COF shell thickness,
      accessible surface modification, and improved solution dispersibility as well as
      maintenance of high surface area, periodic micropores, and superior magnetic
      responsiveness. Additionally, the photothermal conversion effect is demonstrated
      for the first time on the nanoCOF layers upon exposure to near infrared light,
      providing convincing evidence for potential use in phototherapy.

PMID- 27709770
TI  - Health Professionals' Perceptions of the Effects of Exercise on Joint Health in
      Rheumatoid Arthritis Patients.
AB  - OBJECTIVES: Although exercise is an important factor in the management of
      rheumatoid arthritis (RA), research indicates that patients perceive that health
      professionals (HPs) are uncertain about the place of exercise in treatment and
      its relationship with joint damage. The present study investigated the
      perceptions of HPs regarding the effects of exercise on joint health in RA
      patients. METHODS: A questionnaire investigating perceptions of exercise and
      joint health was distributed via professional networks and websites. Confirmatory
      factor analysis (CFA) was used to analyse questionnaire data and develop a focus
      group interview guide. Focus groups were conducted with multidisciplinary teams
      (MDTs) of rheumatology HPs and analysed using framework analysis. RESULTS: A
      total of 137 rheumatology HPs (95 female; 27-65 years of age) completed
      questionnaires. CFA showed that a four-factor model provided a marginally
      acceptable fit. Analysis of four focus groups (n = 24; 19 female; 30-60 years of
      age) identified five themes relating to HPs' perceptions of exercise and joint
      health in RA patients: 'Exercise is beneficial', 'Concerns about damage to
      joints', 'Patients have barriers to exercise', 'HP knowledge differs' and
      'Patients may think service delivery is vague'. CONCLUSIONS: HPs were highly
      aware of the benefits and importance of exercise for RA patients. However, to
      remove the patient perception that HPs lack certainty and clarity regarding
      exercise it is important to ensure: (i) consistent promotion of exercise across
      the whole MDT; (ii) clear provision of information regarding rest, joint
      protection and exercise; (iii) HP education to ensure consistent, accurate
      knowledge, and understanding of the potential for conflicting advice when
      promoting exercise as part of an MDT. Copy (c) 2016 John Wiley & Sons, Ltd.

PMID- 27709771
TI  - [2+1] Cycloaddition Affording Methylene- and Vinylidenecyclopropane Derivatives:
      A Journey around the Reactivity of Metal-Phosphinito-Phosphinous Acid Complexes.
AB  - Metal-phosphinito-phosphinous acid complexes are interesting catalysts exhibiting
      unique reactivities. In this account, we intend to provide a clear overview of
      palladium- and platinum-phosphinito-phosphinous acid complexes, their preparation
      from secondary phosphine oxides, and their applications in catalysis. They have
      been mainly used to develop [2+1] cycloadditions to afford methylenecyclopropane
      derivatives using norbornenes and various alkynes as partners. As a function of
      the catalyst, the reaction conditions, or the nature of the reagents, different
      synthetic transformations have been observed: [2+1] cycloadditions, giving rise
      to either alkylidenecyclopropanes or vinylidenecyclopropanes; tandem [2+1]/[3+2]
      cycloadditions, and so forth. The mechanisms of these reactions have been studied
      to rationalize the different reactivities observed.

PMID- 27709772
TI  - Facile preparation of polydopamine-coated imprinted polymers on the surface of
      SiO2 for estrone capture in milk samples.
AB  - Estrone molecularly imprinted polymers were synthesized through the self
      polymerization of dopamine on the surface of silica gels, which had the
      characteristics of mild polymerization conditions, simple reaction procedure and
      good specific recognition ability for estrone. The estrone molecularly imprinted
      polymers were characterized by scanning electron microscopy, Fourier transform
      infrared spectroscopy, thermogravimetric analysis, elemental analysis and
      nitrogen adsorption-desorption tests. The characterization confirmed that the
      imprinted polymers were successfully grafted on the surface of silica gels.
      Through investigating the adsorption performance, the prepared estrone
      molecularly imprinted polymers exhibited high adsorption capacity, fast mass
      transfer, as well as excellent selectivity toward estrone. The estrone
      molecularly imprinted polymers as the solid-phase extraction adsorbent coupled
      with high-performance liquid chromatography was developed to determine estrone
      from the milk samples. The developed estrone molecularly imprinted polymer solid
      phase extraction with high-performance liquid chromatography method exhibited
      satisfactory specificity, precision, accuracy and good linearity relationship in
      the range of 0.2-20 MUg/mL. The developed method is simple, fast, effective and
      high specificity method and it provides a new method to detect the residues of
      estrone in animal foods.

PMID- 27709773
TI  - Lithography-Free Fabrication of Silica Nanocylinders with Suspended Gold
      Nanorings for LSPR-Based Sensing.
AB  - Tunable plasmonic platforms are important for a variety of applications such as
      photovoltaics, LED's, optoelectronics, medical research, and biosensors. In
      particular, development of label-free plasmonic biosensors is one of the key
      research areas that utilizes plasmonic nanostructures for detection of
      biologically relevant molecules at low concentrations. The authors have developed
      a cost-effective, fast, and lithography-free method to fabricate transparent
      fused silica nanocylinders. The technique allows tuning of nanocylinder height,
      diameter, and density and can be scaled to large surface areas, such as 8 in.
      wafers. The authors demonstrate that gold coated nanocylinders support localized
      surface plasmon resonances (LSPR) from visible to near infrared wavelengths. The
      plasmonic platform can be characterized as suspended gold nanorings and exhibits
      a sensitivity of 658 nm RIU-1 with a figure-of-merit of 10, comparable to other
      state-of-the-art LSPR sensing platforms that utilize more complex nanofabrication
      pathways. It was observed that the LSPR peak positions can be controlled by
      varying the geometry of the nanocylinders. The authors illustrate surface
      functionalization, biosensing, and surface regeneration properties of the
      platform using thiols and detection of bovine serum albumin (BSA). The observed
      LSPR shifts for 11-mercaptoundecanoic acid and BSA was 12 and 26 nm,
      respectively.

PMID- 27709775
TI  - Nickel- and Photoredox-Catalyzed Cross-Coupling Reactions of Aryl Halides with 4
      Alkyl-1,4-dihydropyridines as Formal Nucleophilic Alkylation Reagents.
AB  - A combination of nickel and photoredox catalysts promoted novel cross-coupling
      reactions of aryl halides with 4-alkyl-1,4-dihydropyridines. 4-Alkyl-1,4
      dihydropyridines act as formal nucleophilic alkylation reagents through a
      photoredox-catalyzed carbon-carbon (C-C) bond-cleavage process. The present
      strategy provides an alternative to classical carbon-centered nucleophiles, such
      as organometallic reagents.

PMID- 27709774
TI  - Miniature PCR based portable bioaerosol monitor development.
AB  - AIMS: A portable bioaerosol monitor is greatly demanded technology in many areas
      including air quality control, occupational exposure assessment and health risk
      evaluation, environmental studies and, especially, in defence and bio-terrorism
      applications. Our recent groundwork allowed us to formulate the concept of a
      portable bioaerosol monitor, which needs to be light, user friendly, reliable and
      capable of detecting airborne pathogens within 1-1.5 h on the spot. METHODS AND
      RESULTS: Conceptually, the event of a bioaerosol concentration burst is
      determined by triggers to commence the representative air sampling with
      sequential real-time polymerase chain reaction (PCR) confirmation of the targeted
      micro-organism present in the air. To minimize reagent consumption and idle
      running of the technology, an event of a bioaerosol burst is confirmed by three
      parameters: aerosol particle size, concentration and composition. Only particle
      sizes above 200 nm attract interest in the bioaerosol. Only an elevated aerosol
      concentration above the threshold (background aerosol concentration) is a signal
      to commence the analytical procedure. The combination of our previously developed
      personal bioaerosol sampler, aerosol particle counter based trigger and portable
      real-time PCR device formed the basis of the bioaerosol monitoring technology.
      The portable real-time PCR device was advanced to provide internally controlled
      detection, significantly reducing false-positive alarms. CONCLUSIONS: The
      technique is capable of detecting selected airborne micro-organisms on the spot
      within 30-80 min, depending on the genome organization of the particular strain.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Due to recent outbreaks of infectious
      airborne diseases and the continuing threat of intentionally released bioaerosol
      attacks, investigations into the possibility of the early and reliable detection
      of pathogenic micro-organisms in the air is becoming increasingly important. The
      proposed technology consisting of a bioaerosol sampler, technology trigger and
      PCR device is capable of detecting selected airborne micro-organisms on the spot
      within a short time period.

PMID- 27709776
TI  - Embedding Au Quantum Dots in Rimous Cadmium Sulfide Nanospheres for Enhanced
      Photocatalytic Hydrogen Evolution.
AB  - Rational design and development of new-generation photocatalysts with high
      hydrogen evolution activity is recognized as an effective strategy to settle
      energy crisis. To this regard, hybrid photocatalysts of Au quantum dots embedded
      in rimous cadmium sulfide nanospheres are synthesized by using a simple
      hydrothermal process followed by photoreduction. The rimous cadmium sulfide
      nanospheres with rough surface and irregular fissures greatly strengthen their
      adhesion and interaction with Au quantum dots, which effectively facilitates the
      separation, restrains the recombination, and accelerates the consumption of
      photoinduced electron-hole pairs. Impressively, the highest photocatalytic
      activity for hydrogen generation (601.2 MUmol h-1 g-1 ) and organic pollutant
      degradation (100% degradation in 80 min) is obtained by adjusting the Au mass
      loading to achieve uniform distribution. This work paves new way to the
      exploitation of highly efficient metal/semiconductor hybrid photocatalysts for
      clean energy generation and environment restoration.

PMID- 27709777
TI  - Valproic acid: a relevant thromboprophylactic strategy?

PMID- 27709778
TI  - Liver fibrosis with hypereosinophilia causing transient abnormal myelopoiesis.
AB  - Transient abnormal myelopoesis is mostly self-resolving and has a good prognosis,
      but some patients subsequently die of liver fibrosis. We report the case of an
      infant with Down syndrome who developed life-threatening liver fibrosis at the
      same time as the blasts were about to disappear. This patient also had a marked
      increase in eosinophils, which were possibly harboring a GATA1 mutation and were
      expressing a high level of platelet-derived growth factor-B mRNA; these may have
      been involved in the development of liver fibrosis. Low-dose cytosine arabinoside
      therapy effectively treated both hypereosinophilia and liver fibrosis.

PMID- 27709779
TI  - Helium Ion Microscope Fabrication Causing Changes in the Structure and Mechanical
      Behavior of Silicon Micropillars.
AB  - Silicon is used as a prominent case to demonstrate the dramatic effects of helium
      ion microscope nanofabrication. Structurally, a submicrometer Si pillar can turn
      completely amorphous at He+ doses typically used for micromachining, forming
      nanobubbles at higher doses. In terms of mechanical properties, the flow stress
      decreases markedly with increasing dosage, and the softened amorphous Si exhibits
      spread-out plastic flow.

PMID- 27709780
TI  - Construction of Asymmetrical Hexameric Biomimetic Motors with Continuous Single
      Directional Motion by Sequential Coordination.
AB  - The significance of bionanomotors in nanotechnology is analogous to mechanical
      motors in daily life. Here the principle and approach for designing and
      constructing biomimetic nanomotors with continuous single-directional motion are
      reported. This bionanomotor is composed of a dodecameric protein channel, a six
      pRNA ring, and an ATPase hexamer. Based on recent elucidations of the one-way
      revolving mechanisms of the phi29 double-stranded DNA (dsDNA) motor, various RNA
      and protein elements are designed and tested by single-molecule imaging and
      biochemical assays, with which the motor with active components has been
      constructed. The motor motion direction is controlled by three operation
      elements: (1) Asymmetrical ATPase with ATP-interacting domains for alternative
      DNA binding/pushing regulated by an arginine finger in a sequential action
      manner. The arginine finger bridges two adjacent ATPase subunits into a non
      covalent dimer, resulting in an asymmetrical hexameric complex containing one
      dimer and four monomers. (2) The dsDNA translocation channel as a one-way valve.
      (3) The hexameric pRNA ring geared with left-/right-handed loops. Assessments of
      these constructs reveal that one inactive subunit of pRNA/ATPase is sufficient to
      completely block motor function (defined as K = 1), implying that these
      components work sequentially based on the principle of binomial distribution and
      Yang Hui's triangle.

PMID- 27709781
TI  - Activation of ATP-sensitive potassium channels facilitates the function of human
      endothelial colony-forming cells via Ca2+ /Akt/eNOS pathway.
AB  - Accumulating data, including those from our laboratory, have shown that the
      opening of ATP-sensitive potassium channels (KATP ) plays a protective role in
      pulmonary vascular diseases (PVD). As maintainers of the endothelial framework,
      endothelial colony-forming cells (ECFCs) are considered excellent candidates for
      vascular regeneration in cases of PVD. Although KATP openers (KCOs) have been
      demonstrated to have beneficial effects on endothelial cells, the impact of KATP
      on ECFC function remains unclear. Herein, this study investigated whether there
      is a distribution of KATP in ECFCs and what role KATP play in ECFC modulation. By
      human ECFCs isolated from adult peripheral blood, KATP were confirmed for the
      first time to express in ECFCs, comprised subunits of Kir (Kir6.1, Kir6.2) and
      SUR2b. KCOs such as the classical agent nicorandil (Nico) and the novel agent
      iptakalim (Ipt) notably improved the function of ECFCs, promoting cell
      proliferation, migration and angiogenesis, which were abolished by a non
      selective KATP blocker glibenclamide (Gli). To determine the underlying
      mechanisms, we investigated the impacts of KCOs on CaMKII, Akt and endothelial
      nitric oxide synthase pathways. Enhanced levels were detected by western
      blotting, which were abrogated by Gli. This suggested an involvement of Ca2+
      signalling in the regulation of ECFCs by KATP . Our findings demonstrated for the
      first time that there is a distribution of KATP in ECFCs and KATP play a vital
      role in ECFC function. The present work highlighted a novel profile of KATP as a
      potential target for ECFC modulation, which may hold the key to the treatment of
      PVD.

PMID- 27709783
TI  - Preconcentration and determination of ceftazidime in real samples using
      dispersive liquid-liquid microextraction and high-performance liquid
      chromatography with the aid of experimental design.
AB  - A rapid and simple method for the extraction and preconcentration of ceftazidime
      in aqueous samples has been developed using dispersive liquid-liquid
      microextraction followed by high-performance liquid chromatography analysis. The
      extraction parameters, such as the volume of extraction solvent and disperser
      solvent, salt effect, sample volume, centrifuge rate, centrifuge time, extraction
      time, and temperature in the dispersive liquid-liquid microextraction process,
      were studied and optimized with the experimental design methods. Firstly, for the
      preliminary screening of the parameters the taguchi design was used and then, the
      fractional factorial design was used for significant factors optimization. At the
      optimum conditions, the calibration curves for ceftazidime indicated good
      linearity over the range of 0.001-10 MUg/mL with correlation coefficients higher
      than the 0.98, and the limits of detection were 0.13 and 0.17 ng/mL, for water
      and urine samples, respectively. The proposed method successfully employed to
      determine ceftazidime in water and urine samples and good agreement between the
      experimental data and predictive values has been achieved.

PMID- 27709782
TI  - A proteomics approach to identifying novel protein targets involved in erinacine
      A-mediated inhibition of colorectal cancer cells' aggressiveness.
AB  - Erinacine A, a major active component of a diterpenoid derivative isolated from
      Hericium erinaceus mycelium, has been demonstrated to exert anticancer effects.
      Herein, we present an investigation of the molecular mechanism of erinacine A
      induction associated with cancer cells' aggressive status and death. A proteomic
      approach was used to purify and identify the differentially expressed proteins
      following erinacine A treatment and the mechanism of its action in apoptotic and
      the targets of erinacine A. Our results demonstrate that erinacine A treatment of
      HCT-116 and DLD-1 cells increased cell cytotoxicity and reactive oxygen species
      (ROS) production as well as decreased cell proliferation and invasiveness. Ten
      differentially displayed proteins were determined and validated in vitro and in
      vivo between the erinacine A-treated and untreated groups. In addition, erinacine
      A time-dependent induction of cell death and inhibitory invasiveness was
      associated with sustained phosphorylation of the PI3K/mTOR/p70S6K and
      ROCK1/LIMK2/Cofilin pathways. Furthermore, we demonstrated that erinacine A
      induced HCT-116 and DLD-1 cells viability and anti-invasion properties by up
      regulating the activation of PI3K/mTOR/p70S6K and production of ROS. Experiments
      involving specific inhibitors demonstrated that the differential expression of
      cofilin-1 (COFL1) and profilin-1 (PROF1) during erinacine A treatment could be
      involved in the mechanisms of HCT-116 and DLD-1 cells death and decreased
      aggressiveness, which occurred via ROCK1/LIMK2/Cofilin expression, with
      activation of the PI3K/mTOR/p70S6K signalling pathway. These findings elucidate
      the mechanism of erinacine A inhibiting the aggressive status of cells by
      activating PI3K/mTOR/p70S6K downstream signalling and the novel protein targets
      COF1 and PROF1; this could be a good molecular strategy to limit the
      aggressiveness of CRC cells.

PMID- 27709784
TI  - Morin hydrate promotes inner ear neural stem cell survival and differentiation
      and protects cochlea against neuronal hearing loss.
AB  - We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs)
      isolated from mouse inner ear and its potential in protecting neuronal hearing
      loss. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and
      bromodeoxyuridine incorporation assays were employed to assess the effect of
      morin hydrate on the viability and proliferation of in vitro NSC culture. The
      NSCs were then differentiated into neurons, in which neurosphere formation and
      differentiation were evaluated, followed by neurite outgrowth and neural
      excitability measurements in the subsequent in vitro neuronal network.
      Mechanotransduction of cochlea ex vivo culture and auditory brainstem responses
      threshold and distortion product optoacoustic emissions amplitude in mouse
      ototoxicity model were also measured following gentamicin treatment to
      investigate the protective role of morin hydrate against neuronal hearing loss.
      Morin hydrate improved viability and proliferation, neurosphere formation and
      neuronal differentiation of inner ear NSCs, and promoted in vitro neuronal
      network functions. In both ex vivo and in vivo ototoxicity models, morin hydrate
      prevented gentamicin-induced neuronal hearing loss. Morin hydrate exhibited
      potent properties in promoting growth and differentiation of inner ear NSCs into
      functional neurons and protecting from gentamicin ototoxicity. Our study supports
      its clinical potential in treating neuronal hearing loss.

PMID- 27709785
TI  - Plasmonic Metasurfaces Based on Nanopin-Cavity Resonator for Quantitative
      Colorimetric Ricin Sensing.
AB  - In view of the toxic potential of a bioweapon threat, rapid visual recognition
      and sensing of ricin has been of considerable interest while remaining a
      challenging task up to date. In this study, a gold nanopin-based colorimetric
      sensor is developed realizing a multicolor variation for ricin qualitative
      recognition and analysis. It is revealed that such plasmonic metasurfaces based
      on nanopin-cavity resonator exhibit reflective color appearance, due to the
      excitation of standing-wave resonances of narrow bandwidth in visible region.
      This clear color variation is a consequence of the reflective color mixing
      defined by different resonant wavelengths. In addition, the colored metasurfaces
      appear sharp color difference in a narrow refractive index range, which makes
      them especially well-suited for sensing applications. Therefore, this antibody
      functionalized nanopin-cavity biosensor features high sensitivity and fast
      response, allowing for visual quantitative ricin detection within the range of 10
      120 ng mL-1 (0.15 * 10-9 -1.8 * 10-9 m), a limit of detection of 10 ng mL-1 , and
      the typical measurement time of less than 10 min. The on-chip integration of such
      nanopin metasurfaces to portable colorimetric microfluidic device may be
      envisaged for the quantitative studies of a variety of biochemical molecules.

PMID- 27709787
TI  - Trace determination of organophosphate esters in environmental water samples with
      an ionogel-based nanoconfined ionic liquid fiber coating for solid-phase
      microextraction with gas chromatography and flame photometric detection.
AB  - Organophosphate esters, widely used as flame retardants and plasticizers, are
      regarded as a class of emerging pollutants. In this work, a novel approach was
      developed for the fabrication of a solid-phase microextraction fiber by using
      hybrid silica-based materials with immobilized ionic liquids with sol-gel
      technology, and the prepared solid-phase microextraction fiber was then coupled
      with gas chromatography and flame photometric detection for the analysis of six
      organophosphate esters. The high loading of 1-hexadecyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide was confined within the hybrid network. The
      developed solid-phase microextraction fiber possesses a coating thickness of ~35
      MUm with good thermal stability and long lifetime. The parameters affecting the
      extraction efficiency such as extraction time, temperature, pH, and ionic
      strength of the sample solution were optimized. Under the optimized conditions,
      the limits of detection were in the range of 0.04-0.95 MUg L-1 , and the
      precision of the method assessed with repeatability and reproducibility of (RSD%)
      ?13 and ?29%, respectively. The proposed method was successfully applied to
      determine the six organophosphate esters in three real water samples, with
      recoveries in the range of 64.8-125.4% at two different spiking concentration
      levels. As a result, the proposed method demonstrated its potential for
      application in trace determination of organophosphate esters in actual water
      samples.

PMID- 27709786
TI  - RGB and HSV quantitative analysis of autofluorescence bronchoscopy used for
      characterization and identification of bronchopulmonary cancer.
AB  - Autofluorescence bronchoscopy (AFB) shows good sensitivity in detecting dysplasia
      and bronchopulmonary cancer. However, the poor specificity of AFB would lead to
      excessive biopsy. The aim of the study is to establish a more effective
      quantitative method (optimal identification index and reference value) for
      characterizing the AFB images within the region of interest and discuss AFB's
      significance in the diagnosis of central-type lung cancer. A total of 218
      suspected lung cancer patients were enrolled in this study. A quantitative
      analysis based on color space (red, green, blue[RGB] and HSV system) was
      conducted and the result was compared with the final diagnosis obtained by the
      pathology of biopsy. Cases were divided into different groups according to the
      pathological diagnosis of normal bronchial mucosa, inflammation, low-grade
      preinvasive (LGD), high-grade preinvasive (HGD), and invasive cancer.
      Quantitative analyses in multi-color spaces for the lesions showed by AFB images
      were conducted by software MATLAB. Finally, there is statistical significance
      among the different groups in some parameter in RGB and HSV system. So, both RGB
      and HSV quantitative analysis of autofluorescence bronchoscopy are useful to
      define benign and malignant diseases, which can objectively guide the
      bronchoscopist in selecting sites for biopsy with good pathologic correlation.

PMID- 27709788
TI  - Micro- and Nano-Liquid Phases Coexistent with Ice as Separation and Reaction
      Media.
AB  - Ice has a variety of scientifically interesting features, some of which have not
      been reasonably interpreted despite substantial efforts by researchers. Most
      chemical studies of ice have focused on the elucidation of its physicochemical
      nature and its roles in the natural environment. Ice often contains impurities,
      such as salts, and in such cases, a liquid phase coexists with solid ice over a
      wide temperature range. This impure ice also acts as a cryoreactor, governing the
      circulation of chemical species of environmental importance. Reactions and
      phenomena occurring in this liquid phase show features different from those seen
      in normal bulk aqueous solutions. In the present account, we discuss the chemical
      characteristics of the liquid phase that develops in a frozen aqueous phase and
      show how novel analytical systems can be designed based on he features of the
      liquid phase which are predictable in some cases but unpredictable in others.

PMID- 27709790
TI  - Erratum.

PMID- 27709789
TI  - Comprehensive study of the macropore and mesopore size distributions in polymer
      monoliths using complementary physical characterization techniques and liquid
      chromatography.
AB  - Poly(styrene-co-divinylbenzene) monolithic stationary phases with two different
      domain sizes were synthesized by a thermally initiated free-radical
      copolymerization in capillary columns. The morphology was investigated at the
      meso- and macroscopic level using complementary physical characterization
      techniques aiming at better understanding the effect of column structure on
      separation performance. Varying the porogenic solvent ratio yielded materials
      with a mode pore size of 200 nm and 1.5 MUm, respectively. Subsequently, nano
      liquid chromatography experiments were performed on 200 MUm id * 200 mm columns
      using unretained markers, linking structure inhomogeneity to eddy dispersion.
      Although small-domain-size monoliths feature a relatively narrow macropore-size
      distribution, their homogeneity is compromised by the presence of a small number
      of large macropores, which induces a significant eddy-dispersion contribution to
      band broadening. The small-domain size monolith also has a relatively steep mass
      transfer term, compared to a monolith containing larger globules and macropores.
      Structural inhomogeneity was also studied at the mesoscopic level using gas
      adsorption techniques combined with the non-local-density-function-theory. This
      model allows to accurately determine the mesopore properties in the dry state.
      The styrene-based monolith with small domain size has a distinctive trimodal
      mesopore distribution with pores of 5, 15, and 25 nm, whereas the monolith with
      larger feature sizes only contains mesopores around 5 nm in size.

PMID- 27709792
TI  - Investigating the work-family conflict and health link: Repetitive thought as a
      mechanism.
AB  - Research is needed to investigate mechanisms linking work-family conflict to poor
      health in working adults. We took a novel approach to build on extant studies by
      testing a potential mechanism in these associations - repetitive thought. Data
      came from a sample of 203 partnered working adults. There were significant direct
      effects of work-family conflict with lower life satisfaction, positive affect,
      and perceived health as well as greater fatigue. As for total effects, work
      family conflict was significantly associated with all health outcomes - life
      satisfaction, positive affect, negative affect, fatigue, perceived health, and
      chronic health conditions - in the expected directions through repetitive
      thought. This study provides support that repetitive thought is one potential
      mechanism of how work-family conflict can take a toll on psychological and
      physical health. Findings are discussed in relation to improving workplace
      policies to improve the health of working adults managing work-family conflict.

PMID- 27709793
TI  - PD-1 expression on the surface of peripheral blood CD4+ T cell and its
      association with the prognosis of patients with diffuse large B-cell lymphoma.
AB  - The aim of the study was to investigate the relationship between PD-1 expression
      on the surface of CD4+ T cells and prognosis of patients with diffuse large B
      cell lymphoma (DLBCL). Sixty patients who were newly diagnosed with DLBCL and 39
      healthy controls were enrolled. In CD4+ T cells of DLBCL patients, the median MFI
      of PD-1 were 541.5 (range: 348.25-758.75), significantly higher than 250 (range:
      211-326) in healthy controls (P < 0.001). The ZAP70, PI3K, and NFAT mRNA
      expression levels of patients were 0.47, 0.47, and 0.62 times, respectively, of
      those of the healthy controls (P < 0.05). In patients with the percentage of PD-1
      on CD4+ T cells >=30.25%, their EFS and OS were significantly lower than patients
      with PD-1+ CD4+ T cells <30.25% (P < 0.05). The possible explanation is that high
      PD-1 expression on CD4+ cells of DLBCL patients may impair T-cell function and
      thus contribute to poor prognosis. There was no relationship between PD-1 surface
      expression on CD4+ T cells and PD-1 expression within the biopsy of tumor
      microenvironments from DLBCL patients.

PMID- 27709794
TI  - Addition of a dipeptidyl peptidase-4 inhibitor, sitagliptin, to ongoing therapy
      with the glucagon-like peptide-1 receptor agonist liraglutide: A randomized
      controlled trial in patients with type 2 diabetes.
AB  - AIM: To determine whether the addition of sitagliptin to pre-existing therapy
      with liraglutide changes glycaemic excursions after a mixed meal. METHODS: A
      total of 16 patients with type 2 diabetes treated with metformin and liraglutide
      (1.2 mg/d for >=2 weeks) were randomized (sealed envelopes), within a cross-over
      design, to be studied on two occasions, after an overnight fast, with (1)
      sitagliptin (100 mg orally) and (2) placebo (patients and care givers blinded)
      administered 60 minutes before a mixed meal, or vice versa. Glucose excursions
      (incremental area under the curve [AUC]; primary endpoint) and insulin, C
      peptide, glucagon and incretin concentrations were measured. The study setting
      was a metabolic study unit at a specialized diabetes hospital. RESULTS: All 16
      patients completed the study and were analysed. Glucose (AUCglucose 319 +/- 30
      [placebo] vs 315 +/- 18 mmol.L-1 .min-1 [sitagliptin], Delta 7 [95% confidence
      interval -50 to 63] mmol.L-1 .min-1 ), insulin, C-peptide and glucagon
      concentrations were not affected significantly by sitagliptin treatment ( P = .60
      1.00). Intact glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) concentrations were augmented by sitagliptin, by
      78.4% and 90.2%, respectively (both P < .0001). The influence of sitagliptin
      treatment on incretin plasma concentrations was similar to previously published
      results obtained in patients with type 2 diabetes on metformin treatment only.
      CONCLUSIONS: Sitagliptin, in patients already treated with a GLP-1 receptor
      agonist (liraglutide), increased intact GLP-1 and GIP concentrations, but with
      marginal, non-significant effects on glycaemic control. GLP-1 receptors have
      probably been maximally stimulated by liraglutide. Our findings do not support
      combination treatment with GLP-1 receptor agonists and DPP-4 inhibitors, but
      longer-term trials are needed to support clinical recommendations.

PMID- 27709796
TI  - Pentaindenocorannulene: Properties, Assemblies, and C60 Complex.
AB  - Pentaindenocorannulene (C50 H20  , 1), a deep bowl polynuclear aromatic
      hydrocarbon, accepts 4 electrons, crystallizes in columnar bowl-in-bowl
      assemblies and forms a nested C60 @12 complex. Spectra, structures and
      computations are presented.

PMID- 27709795
TI  - Radiofrequency ablation versus stereotactic body radiotherapy for small
      hepatocellular carcinoma: a Markov model-based analysis.
AB  - The aim of this study is to compare radiofrequency ablation (RFA) with
      stereotactic body radiotherapy (SBRT) for hepatocellular carcinomas (HCC) smaller
      than 3 cm. A Markov cohort model was developed to simulate a cohort of patients
      aged 60-65 years with small HCCs who had undergone either RFA or SBRT and were
      followed up over their remaining life expectancy. The inclusion criteria were:
      (1) HCC <=3 cm in diameter with <= 3 nodules; (2) absence of extrahepatic
      metastasis or portal/hepatic vein invasion; (3) Child-Pugh Class A or B. Twenty
      thousand virtual patients were randomly assigned to undergo RFA or SBRT.
      Predicted life expectancy was 6.452 and 6.371 years in the RFA and SBRT groups,
      respectively. The probability distributions of the expected overall survival were
      nearly identical. The 95% confidence intervals were 6.25-6.66 and 6.17-6.58 years
      for RFA and SBRT, respectively. The difference between RFA and SBRT was
      insignificant (P = 0.2884). Two-way sensitivity analysis demonstrated that if the
      tumor is 2-3 cm, SBRT is the preferred treatment option. Our Markov model has
      shown that expected overall survival of SBRT is nearly identical to RFA in HCCs
      smaller than 3 cm, but SBRT may have an advantage for tumors 2 cm and larger. A
      randomized trial is required to confirm these findings.

PMID- 27709797
TI  - Homoharringtonine combined with aclarubicin and cytarabine synergistically
      induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated
      cleavage of the AML1-ETO oncoprotein.
AB  - Homoharringtonine combined with aclarubicin and cytarabine (HAA) is a highly
      effective treatment for acute myeloid leukemia (AML), especially for t(8;21) AML.
      However, the underlying mechanisms by which HAA kills t(8;21) AML cells remain
      unclear. In this study, SKNO-1 and Kasumi-1 cells with t(8;21) were used.
      Compared with individual or pairwise administration of homoharringtonine,
      aclarubicin, or cytarabine, HAA showed the strongest inhibition of growth and
      induction of apoptosis in SKNO-1 and Kasumi-1 cells. HAA caused cleavage of the
      AML1-ETO (AE) oncoprotein to form truncated AE (DeltaAE). Pretreatment with the
      caspase-3 inhibitor caspase-3 inhibitor Q-DEVD-OPh (QDO) not only suppressed HAA
      induced apoptosis but also abrogated the cleavage of AE and generation of
      DeltaAE. These results suggest that HAA synergistically induces apoptosis in
      t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO
      oncoprotein, thus providing direct evidence for the strong activity of HAA toward
      t(8;21) AML.

PMID- 27709798
TI  - The E3 ubiquitin ligase RNF135 regulates the tumorigenesis activity of tongue
      cancer SCC25 cells.
AB  - Several E3 ubiquitin ligases have been confirmed that they are related to the
      tumorigenesis. This study aims to find the tongue cancer-related E3 ubiquitin
      ligase. The E3 ubiquitin ligase library was screened. The effect of candidate
      molecule on tongue cancer was validated through cell viability, cell
      proliferation, colony formation, invasive assay in vitro, and the xenograft model
      in vivo. The E3 ubiquitin ligase RNF135 significantly promoted the expression of
      PTEN and TP53 in SCC25 cells. The overexpression of RNF135 inhibited the
      viability, proliferation, and invasion of SCC25 cells. Knockdown of RNF135 had
      the opposite effects. Furthermore, RNF135 regulates the tumorigenesis activity of
      SCC25 cells in vivo. Our results demonstrated that RNF135 had the potential to
      affect the development of the tongue cancer in vitro. The further in vivo study
      is helpful to fully understand the role of it.

PMID- 27709800
TI  - An implicit solver for 1D arterial network models.
AB  - In this study, the 1D blood flow equations are solved using a newly proposed
      enhanced trapezoidal rule method (ETM), which is an extension to the simplified
      trapezoidal rule method. At vessel junctions, the conservation of mass and
      conservation of total pressure are held as system constraints using Lagrange
      multipliers that can be physically interpreted as external flow rates. The ETM
      scheme is compared with published arterial network benchmark problems and a dam
      break problem. Strengths of the ETM scheme include being simple to implement,
      intuitive connection to lumped parameter models, and no restrictive stability
      criteria such as the Courant-Friedrichs-Lewy (CFL) number. The ETM scheme does
      not require the use of characteristics at vessel junctions, or for inlet and
      outlet boundary conditions. The ETM forms an implicit system of equations, which
      requires only one global solve per time step for pressure, followed by flow rate
      update on the elemental system of equations; thus, no iterations are required per
      time step. Consistent results are found for all benchmark cases, and for a 56
      vessel arterial network problem, it gives very satisfactory solutions at a
      spatial and time discretization that results in a maximum CFL of 3, taking 4.44
      seconds per cardiac cycle. By increasing the time step and element size to
      produce a maximum CFL number of 15, the method takes only 0.39 second per cardiac
      cycle with only a small compromise on accuracy.

PMID- 27709801
TI  - Enzymatic Kinetic Resolution of Secondary Alcohols Using an Ionic Anhydride
      Generated In Situ.
AB  - We developed a method for the resolution of secondary alcohols using an ionic
      anhydride acylating agent prepared directly in the reaction medium containing the
      biocatalyst Candida antarctica lipase B (CALB). NMR studies showed that mixing
      all components at the same time does not interfere with the coupling reaction or
      the enzymatic activity. After optimization of the reaction conditions, the method
      allowed the resolution of a number of substrates in very high conversions (46-48
      %) and enantiomeric ratios (E>170) along with an easy recovery of both
      enantiomers without the need for preparative chromatographic separation.
      Additionally, both the starting ionic acid and the biocatalyst could be recovered
      and reused up to nine cycles without significant loss of enantioselectivity.

PMID- 27709799
TI  - Neurotrophic Factor-alpha1: A Key Wnt-beta-Catenin Dependent Anti-Proliferation
      Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell
      Differentiation to Astrocytes in Neurodevelopment.
AB  - Embryonic neurodevelopment involves inhibition of proliferation of multipotent
      neural stem cells (NSCs) followed by differentiation into neurons, astrocytes and
      oligodendrocytes to form the brain. We have identified a new neurotrophic factor,
      NF-alpha1, which inhibits proliferation and promotes differentiation of
      NSC/progenitors derived from E13.5 mouse cortex. Inhibition of proliferation of
      these cells was mediated through negatively regulating the Wnt pathway and
      decreasing beta-catenin. NF-alpha1 induced differentiation of NSCs to astrocytes
      by enhancing Glial Fibrillary Acidic Protein (GFAP) expression through activating
      the ERK1/2-Sox9 signaling pathway. Cultured E13.5 cortical stem cells from NF
      alpha1-knockout mice showed decreased astrocyte numbers compared to wild-type
      mice, which was rescued by treatment with NF-alpha1. In vivo, immunocytochemistry
      of brain sections and Western blot analysis of neocortex of mice showed a gradual
      increase of NF-alpha1 expression from E14.5 to P1 and a surge of GFAP expression
      at P1, the time of increase in astrogenesis. Importantly, NF-alpha1-Knockout mice
      showed ~49% fewer GFAP positive astrocytes in the neocortex compared to WT mice
      at P1. Thus, NF-alpha1 is critical for regulating antiproliferation and cell fate
      determination, through differentiating embryonic stem cells to GFAP-positive
      astrocytes for normal neurodevelopment. Stem Cells 2017;35:557-571.

PMID- 27709803
TI  - Inter-scan and inter-observer tumour volume delineation variability on cone beam
      computed tomography in patients treated with stereotactic body radiation therapy
      for early-stage non-small cell lung cancer.
AB  - INTRODUCTION: Quantification of volume changes on cone beam computed tomography
      (CBCT) during lung stereotactic body radiation therapy (SBRT) for non-small cell
      lung cancer (NSCLC) may provide a useful radiological marker for radiation
      response and for adaptive treatment planning. This study quantifies inter-scan
      and inter-observer variability in tumour volume delineation on CBCT. METHODS:
      Three clinicians independently contoured the primary gross tumour volume (GTV)
      manually on CBCTs taken immediately before SBRT treatment (pre) and after the
      same SBRT treatment (post) for 19 NSCLC patients. Relative volume differences
      (RVD) were calculated between the pre- and post-CBCTs for a given treatment and
      between any two of three observers for a given CBCT. Coefficient of variation
      (CV) was used to quantitatively measure and compare the extent of variability.
      RESULTS: Inter-observer variability had a significantly higher CV of 0.15 +/-
      0.13 compared to inter-scan CV of 0.03 +/- 0.04 with P < 0.0001. The greatest
      variability was observed with tumours (<2 cm in diameter) versus larger tumours
      with 95% limit of agreement (LOA) (Mean +/- Standard Deviation) of 1.90% +/-
      19.55% vs. -0.97% +/- 12.26% for inter-scan RVD and 29.99% +/- 73.84% vs. 9.37%
      +/- 29.95% for inter-observer RVD respectively. CONCLUSIONS: Inter-observer
      variability was greater than inter-scan variability for tumour volume delineation
      on CBCT with greatest variability for small tumours (<2 cm in diameter). LOA for
      inter-scan variability (~12%) helps defines a threshold for clinically meaningful
      tumour volume change during SBRT treatment for tumours with diameter greater than
      2 cm, with larger thresholds needed for smaller tumours.

PMID- 27709802
TI  - Association of HLA alleles and haplotypes with CYP21A2 gene p. V282L mutation in
      the Croatian population.
AB  - The CYP21A2 mutations that are in linkage disequilibrium with particular HLA-A, 
      B, -DRB1 alleles/haplotypes, cause deficiency of the 21-hydroxylase enzyme (21
      OHD) and account for the majority of congenital adrenal hyperplasia (CAH) cases.
      The aim of this study was to investigate those associations with the p.V282L
      mutation linked to the non-classical (NC) form of CAH among Croatians. The study
      included parents of patients with the NC form of CAH, positive for the p.V282L
      mutation (N = 55) and cadaveric donor samples (N = 231). All subjects were HLA-A,
      -B, and -DRB1 typed and tested for the presence of the p.V282L mutation. Among
      parents of patients, 92.73% of subjects were positive for the B*14:02 allele and
      almost half of them carried the HLA-A*33:01-B*14:02-DRB1*01:02 haplotype. Among
      cadaveric samples 77 out of 96 subjects positive for the B*14:02 allele had the
      p.V282L mutation. Among them, 37 were positive for the HLA-A*33:01-B*14:02
      DRB1*01:02 haplotype, 23 had the HLA-A*33:01-B*14:02-DRB1*03:01 haplotype, 8 had
      the B*14:02-DRB1*01:02 combination and 5 were carrying the HLA-A*68:02-B*14:02
      DRB1*13:03 haplotype. Only 4 of these subjects were positive for the B*14:02
      allele. HLA-B*14:02 was the only single allele with association that reached
      statistically significant P value (RR = 12.00; P = 0.0024). Haplotypes B*14:02
      DRB1*01:02 (P < 0.001) and HLA-A*68:02-B*14:02-DRB1*13:03 (P < 0.001) as well as
      HLA-A*33:01-B*14:02-DRB1*01:02 and HLA-A*33:01-B*14:02-DRB1*03:01 showed high
      relative risks (RR = 45.00, RR = 41.63 and RR = 36.96, respectively). Our data
      support the previously documented association of the HLA-A*33:01-B*14:02
      DRB1*01:02 haplotype with the p.V282L mutation, but also point out a high
      frequency of the p.V282L mutation among Croatians with HLA-A*33:01-B*14:02
      DRB1*03:01 and HLA-A*68:02-B*14:02-DRB1*13:03 haplotypes.

PMID- 27709805
TI  - The Royal Australian and New Zealand College of Radiologists (RANZCR) 67th Annual
      Scientific Meeting, 13-16 October 2016, Gold Coast, Australia.

PMID- 27709807
TI  - Metagenomics insights into food fermentations.
AB  - This review describes the recent advances in the study of food microbial ecology,
      with a focus on food fermentations. High-throughput sequencing (HTS) technologies
      have been widely applied to the study of food microbial consortia and the
      different applications of HTS technologies were exploited in order to monitor
      microbial dynamics in food fermentative processes. Phylobiomics was the most
      explored application in the past decade. Metagenomics and metatranscriptomics,
      although still underexploited, promise to uncover the functionality of complex
      microbial consortia. The new knowledge acquired will help to understand how to
      make a profitable use of microbial genetic resources and modulate key activities
      of beneficial microbes in order to ensure process efficiency, product quality and
      safety.

PMID- 27709804
TI  - Impaired hepato-renal function defined by the MELD XI score as prognosticator in
      acute heart failure.
AB  - AIM: Multi-organ dysfunction often complicates the natural course of acute heart
      failure (AHF) and identifies patients with poor prognosis. The MELD score (Model
      of End-Stage Liver Dysfunction) combines data reflecting liver and kidney
      function, which makes it a potentially useful tool for the assessment of patients
      with AHF. The aim of this study was to assess the prognostic utility of the MELD
      score in patients with AHF. METHODS AND RESULTS: The MELD score was calculated on
      admission and during hospital stay (days 2-3) using a formula that does not take
      into account the international normalized ratio (MELD XI). The study population
      consisted of 203 AHF patients (mean age 65 +/- 12 years, 76% male). The mean MELD
      XI score was -14.8 +/- 4.5 points on admission and 13.9 +/- 4.3 points during
      hospitalization. Contributors of elevated MELD XI score at baseline and during
      hospital stay were isolated increase in creatinine in 22-25%, isolated increase
      in bilirubin in 17-19%, and abnormal values of both in 40-46% of patients. During
      1-year follow-up, 67 (33%) patients died. After adjustment for well-established
      prognosticators, MELD XI score at baseline and during hospital stay were
      significant predictors of poor outcome [hazard ratio (95% confidence interval):
      1.11 (1.05-1.2) and 1.14 (1.09-1.2), respectively, P < 0.001]. An increase in the
      MELD XI score during hospital stay occurred in 31% of patients and was related to
      increased risk of death at 1 year [1.97 (1.2-3.2), P < 0.005]. CONCLUSIONS:
      Impairment of hepato-renal function defined by the MELD XI score is common and
      carries unfavourable prognosis in AHF patients.

PMID- 27709808
TI  - Psychosocial changes following transition to an aged care home: qualitative
      findings from Iran.
AB  - AIMS AND OBJECTIVES: The study explored the psychosocial effects of transitioning
      from home to an aged care home for older Iranian people. BACKGROUND: Moving from
      one's own home to a communal aged care home is challenging for older people and
      may give rise to numerous psychosocial responses. The extent and intensity of
      such changes have rarely been explored in Middle Eastern countries. DESIGN: Data
      were collected through purposive sampling by in-depth semi-structured interviews
      with 20 participants (17 people living in aged care homes and three formal
      caregivers). All the interviews were recorded and typed, and conventional
      qualitative content analysis was used, eliciting common themes. RESULTS: There
      were four common themes: communication isolation, resource change, monotone
      institutional life and negative emotional response. Participants lost their
      previous support systems when transitioning to an aged care home and were not
      able to establish new ones. Routine care was provided by formal caregivers with
      little attention to individual needs, and minimal support was given to help
      maintain the older person's independence. These losses gave rise to negative
      emotions in some of the participants, depending on their previous lifestyle and
      accommodation arrangements. CONCLUSIONS: The extent and intensity of psychosocial
      changes occurring in most of the participants following their transition to an
      aged care home indicates the need for a review of Iranian aged care services.
      IMPLICATIONS FOR PRACTICE: To assist older Iranian people adapt more readily when
      making the transition to aged care home and to meet their unique psychosocial
      needs, a family-centred approach to service delivery is recommended.

PMID- 27709809
TI  - Regulating Stem Cell Secretome Using Injectable Hydrogels with In Situ Network
      Formation.
AB  - A family of shear-thinning hydrogels for injectable encapsulation and long-term
      delivery (SHIELD) has been designed and synthesized with controlled in situ
      stiffening properties to regulate the stem cell secretome. The authors
      demonstrate that SHIELD with an intermediate stiffness (200-400 Pa) could
      significantly promote the angiogenic potential of human adipose-derived stem
      cells.

PMID- 27709810
TI  - Diagnostic performance of multi-slice CT angiography combined with enterography
      for small bowel obstruction and intestinal ischaemia.
AB  - INTRODUCTION: This study was performed to evaluate the diagnostic performance of
      multi-slice CT angiography combined with enterography in determining the cause
      and location of obstruction as well as intestinal ischaemia in patients with
      small bowel obstruction (SBO). METHODS: This study retrospectively summarized the
      image data of 57 SBO patients who received both multi-slice CT angiography and
      enterography examination between December 2012 and May 2013. The CT diagnoses of
      SBO and intestinal ischaemia were correlated with the findings at surgery or
      digital subtraction angiography, which were set as standard references. RESULTS:
      Multi-slice CT angiography and enterography indicated that the cause of SBO in
      three patients was misjudged, suggesting a diagnostic accuracy of 94.7%. In one
      patient the level of obstruction was incorrect, demonstrating a diagnostic
      accuracy of 98.2%. Based on the results of the receiver operating characteristic
      (ROC) curve analysis, the diagnostic criterion for ischaemic SBO was at least two
      of the four CT signs (circumferential bowel wall thickening, reduced enhancement
      of the intestinal wall, mesenteric oedema and mesenteric vascular engorgement).
      The criterion yielded a sensitivity of 94.4%, a specificity of 92.3%, a positive
      predicted value of 85.0% and a negative predicted value of 97.3%, and the area
      under curve (AUC) was 0.92 (95% CI, 0.85-0.99). CONCLUSION: Multi-slice CT
      angiography and enterography have high diagnostic value in identifying the cause
      and site of SBO. In addition, the suggested diagnostic criterion using CT signs
      is helpful for diagnosing intestinal ischaemia in SBO patients.

PMID- 27709811
TI  - Case report of male breast cancer detected on magnetic resonance imaging.
AB  - Male breast cancers (MBC) are rare, accounting for <1% of all breast cancers. The
      use of magnetic resonance imaging (MRI) for male breast cancer is not generally
      indicated. We present an unusual case where conventional imaging for a suspected
      MBC was equivocal and MRI was required to assist in diagnosis.

PMID- 27709812
TI  - A novel filtration system for point of care washing of cellular therapy products.
AB  - The cell therapy industry would greatly benefit from a simple point of care
      solution to remove dimethylsulphoxide (DMSO) from small-volume thawed cell
      suspensions before injection. A novel dead-end filtration device has been
      designed and validated, which takes advantage of the higher density of thawed
      cell suspensions to remove the DMSO and protein impurities from the cell
      suspension without fouling the filter membrane. The filter was designed to avoid
      fluid circuits and minimize the surface area that is contacted by the cell
      suspension, thus reducing cell losses by design. The filtration process was
      established through optimization of the fluid flow configuration, backflush
      cycles and filter geometry. Overall, this novel filtration device allows for a 1
      ml of thawed cryopreserved cell suspensions, containing 107 cells of a fetal lung
      fibroblast cell line (MRC-5), to be washed in less than 30 min. More than 95% of
      the DMSO and up to 94% of the albumin-fluorescein-isothiocyanate content can be
      removed while the viable cell recovery is higher than 80%. It is also
      demonstrated that this system can be used for bone marrow-derived human
      mesenchymal stem cells with more than 73% cell recovery and 85% DMSO reduction.
      This is the first time that a dead end (normal) filtration process has been used
      to successfully wash high-density human cell suspensions. In practice, this novel
      solid-liquid separation technology fills the need for small-volume washing in
      closed processing systems for cellular therapies. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27709815
TI  - Bismuth Complexes in Phenylazomethine Dendrimers: Controllable Luminescence and
      Emission in the Solid State.
AB  - Dendritic phosphors were obtained by the stepwise integration of BiCl3 in
      phenylazomethine dendrimers. The bismuth-coordinated phenylazomethines displayed
      photoluminescence at 500-800 nm, and the intensity could be tuned by changing the
      stoichiometry of BiCl3 and the dendrimer. This phosphor did not show serious
      luminescence quenching even though the local concentration of BiCl3 in the
      dendrimer was as high as 20 M, and luminescence was also observed in the solid
      state. The absorption and emission properties could be reversibly switched by
      addition of a Lewis base or under electrochemical redox control, which induced
      the reversible complexation of BiCl3 in the dendrimer.

PMID- 27709814
TI  - Determination of differentially regulated proteins upon proteasome inhibition in
      AML cell lines by the combination of large-scale and targeted quantitative
      proteomics.
AB  - The ubiquitin-proteasome pathway (UPP) plays a critical role in the degradation
      of proteins implicated in cell cycle control, signal transduction, DNA damage
      response, apoptosis and immune response. Proteasome inhibitors can inhibit the
      growth of a broad spectrum of human cancer cells by altering the balance of
      intracellular proteins. However, the targets of these compounds in acute myeloid
      leukemia (AML) cells have not been fully characterized. Herein, we combined large
      scale quantitative analysis by SILAC-MS and targeted quantitative proteomic
      analysis in order to identify proteins regulated upon proteasome inhibition in
      two AML cell lines displaying different stages of maturation: immature KG1a cells
      and mature U937 cells. In-depth data analysis enabled accurate quantification of
      more than 7000 proteins in these two cell lines. Several candidates were
      validated by selected reaction monitoring (SRM) measurements in a large number of
      samples. Despite the broad range of proteins known to be affected by proteasome
      inhibition, such as heat shock (HSP) and cell cycle proteins, our analysis
      identified new differentially regulated proteins, including IL-32, MORF family
      mortality factors and apoptosis inducing factor SIVA, a target of p53. It could
      explain why proteasome inhibitors induce stronger apoptotic responses in immature
      AML cells.

PMID- 27709816
TI  - Stereocontrolled Syntheses of Seven-Membered Carbocycles by Tandem Allene
      Aziridination/[4+3] Reaction.
AB  - A tandem allene aziridination/[4+3]/reduction sequence converts simple
      homoallenic sulfamates into densely functionalized aminated cycloheptenes, where
      the relative stereochemistry at five contiguous asymmetric centers can be
      controlled through the choice of the solvent and the reductant. The products
      resulting from this chemistry can be readily transformed into complex molecular
      scaffolds which contain up to seven contiguous stereocenters.

PMID- 27709817
TI  - Tunable Probes with Direct Fluorescence Signals for the Constitutive and
      Immunoproteasome.
AB  - Electrophiles are commonly used for the inhibition of proteases. Notably,
      inhibitors of the proteasome, a central determinant of cellular survival and a
      target of several FDA-approved drugs, are mainly characterized by the reactivity
      of their electrophilic head groups. We aimed to tune the inhibitory strength of
      peptidic sulfonate esters by varying the leaving groups. Indeed, proteasome
      inhibition correlated well with the pKa of the leaving group. The use of
      fluorophores as leaving groups enabled us to design probes that release a
      stoichiometric fluorescence signal upon reaction, thereby directly linking
      proteasome inactivation to the readout. This principle could be applicable to
      other sulfonyl fluoride based inhibitors and allows the design of sensitive
      probes for enzymatic studies.

PMID- 27709813
TI  - Expression of Tim-1 in primary CNS lymphoma.
AB  - Primary central nervous system lymphoma (PCNSL) is a distinct subtype of
      extranodal lymphoma with aggressive clinical course and poor outcome. As
      increased IL-10/IL-6 ratio is recognized in the cerebrospinal fluid (CSF) of
      PCNSL patients, we hypothesized that PCNSL might originate from a population of B
      cells with high IL-10-producing capacity, an equivalent of "regulatory B cells"
      in mice. We intended in this study to clarify whether Tim-1, a molecule known as
      a marker for regulatory B cells in mice, is expressed in PCNSL. By
      immunohistochemical analysis, Tim-1 was shown to be positive in as high as 54.2%
      of PCNSL (26 of 58 samples), while it was positive in 19.1% of systemic diffuse
      large B-cell lymphoma (DLBCL) samples (17 of 89 samples; P < 0.001). Tim-1
      expression positively correlated with IL-10 expression in PCNSL (Cramer's V =
      0.55, P < 0.001), and forced expression of Tim-1 in a PCNSL cell line resulted in
      increased IL-10 secretion, suggesting that Tim-1 is functionally linked with IL
      10 production in PCNSL. Moreover, soluble Tim-1 was detectable in the CSF of
      PCNSL patients, and was suggested to parallel disease activity. In summary, PCNSL
      is characterized by frequent Tim-1 expression, and its soluble form in CSF may
      become a useful biomarker for PCNSL.

PMID- 27709819
TI  - Isotopologous Organotellurium Probes Reveal Dynamic Hypoxia In Vivo with Cellular
      Resolution.
AB  - Changes in the oxygenation state of microenvironments within solid tumors are
      associated with the development of aggressive cancer phenotypes. Factors that
      influence cellular hypoxia have been characterized; however, methods for
      measuring the dynamics of oxygenation at a cellular level in vivo have been
      elusive. We report a series of tellurium-containing isotopologous probes for
      cellular hypoxia compatible with mass cytometry (MC)-technology that allows for
      highly parametric interrogation of single cells based on atomic mass
      spectrometry. Sequential labeling with the isotopologous probes (SLIP) in
      pancreatic tumor xenograft models revealed changes in cellular oxygenation over
      time which correlated with the distance from vasculature, the proliferation of
      cell populations, and proximity to necrosis. SLIP allows for capture of spatial
      and temporal dynamics in vivo using enzyme activated probes.

PMID- 27709820
TI  - Corrigendum: Structure and Composition of the 200 K-Superconducting Phase of H2 S
      at Ultrahigh Pressure: The Perovskite (SH- )(H3 S+ ).

PMID- 27709821
TI  - Corrigendum: Programming A Molecular Relay for Ultrasensitive Biodetection
      through 129 Xe NMR.

PMID- 27709822
TI  - Use of a Catalytic Chiral Leaving Group for Asymmetric Substitutions at sp3 
      Hybridized Carbon Atoms: Kinetic Resolution of beta-Amino Alcohols by p
      Methoxybenzylation.
AB  - A catalytic strategy was developed for asymmetric substitution reactions at sp3 
      hybridized carbon atoms by using a chiral alkylating agent generated in situ from
      trichloroacetimidate and a chiral phosphoric acid. The resulting chiral p
      methoxybenzyl phosphate selectively reacts with beta-amino alcohols rather than
      those without a beta-NH functionality. The use of an electronically and
      sterically tuned chiral phosphoric acid enables the kinetic resolution of amino
      alcohols through p-methoxybenzylation with good enantioselectivity.

PMID- 27709823
TI  - Transition-Metal-Free Synthesis of N-Hydroxy Oxindoles by an Aza-Nazarov-Type
      Reaction Involving Azaoxyallyl Cations.
AB  - A novel transition-metal-free method to construct N-hydroxy oxindoles by an aza
      Nazarov-type reaction involving azaoxyallyl cation intermediates is described. A
      variety of functional groups were tolerated under the weak basic reaction
      conditions and at room temperature. A one-pot process was also developed to make
      the reaction even more practical. This method provides alternative access to
      oxindoles and their biologically active derivatives.

PMID- 27709824
TI  - Form of delivery as a key 'active ingredient' in behaviour change interventions.

PMID- 27709825
TI  - Comparative analysis of the main bioactive components of Xin-Sheng-Hua granule
      and its single herbs by ultrahigh performance liquid chromatography with tandem
      mass spectrometry.
AB  - Xin-Sheng-Hua granule, a representative formula for postpartum hemorrhage, has
      been used clinically to treat postpartum diseases. Its main bioactive components
      comprise aromatic acids, phthalides, alkaloids, flavonoids, and gingerols among
      others. To investigate the changes in main bioactive constituents in its seven
      single herbs before and after compatibility, a rapid, simple, and sensitive
      method was developed for comparative analysis of 27 main bioactive components by
      using ultrahigh-performance liquid chromatography with triple quadrupole
      electrospray tandem mass spectrometry for the first time. The sufficient
      separation of 27 target constituents was achieved on a Thermo Scientific Hypersil
      GOLD column (100 mm * 3 mm, 1.9 MUm) within 20 min under the optimized
      chromatographic conditions. Compared with the theoretical content, the observed
      content of each analyte showed remarkable differences in Xin-Sheng-Hua granule
      except thymine, p-coumaric acid, senkyunolide I, senkyunolide H, and ligustilide;
      the total contents of 27 components increased significantly, and the content
      variation degrees for the different components were gingerols > flavonoids >
      aromatic acids > alkaloids > phthalides. The results could provide a good
      reference for the quality control of Xin-Sheng-Hua granule and might be helpful
      to interpret the drug interactions based on variation of bioactive components in
      formulae.

PMID- 27709826
TI  - Buckwheat bioactive compounds, their derived phenolic metabolites and their
      health benefits.
AB  - SCOPE: Buckwheat (BW) consumption has been associated with a broad range of
      health benefits: antioxidant, anti-inflammatory and anticancer. These beneficial
      effects have been partially related to the presence of flavonoids. However, some
      of these compounds (i.e., rutin and quercetin) are metabolized in the
      gastrointestinal tract generating derived phenolic metabolites. In this study, we
      investigated the biological activity of rutin (Ru), quercetin (Q) an their
      derived phenolic metabolites 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), 3
      hydroxyphenylacetic acid (3-HPAA), and 4-hydroxy-3-methoxyphenylacetic acid
      (homovanillic acid, HVA). METHODS AND RESULTS: Q showed the highest antioxidant
      and reducing activity, and Ru the maximum chelating activity (85.33%).
      Antioxidant activity of 3,4-DHPAA was 5-fold higher than that of HVA, whereas
      their reducing activity was similar. The formation of methylglyoxal (MGO)-BSA and
      glucose-BSA (advanced glycation end products) was inhibited by Ru (98.5 and
      92.7%), Q (95.6 and 89.1%) and 3,4-DHPPA (84.4.6 and 77.5%). Furthermore, Q (10
      50 MUM) and Ru (1-50 MUM) downregulated the release of PGE2 , IL-8 and MCP-1,
      molecules involved in the inflammatory response, in IL1beta-inflamed
      myofibroblasts of colon CCD-18Co. CONCLUSION: This study suggests that BW
      phytochemicals and their phenolic metabolites may be responsible for the
      beneficial effects against chronic diseases attributed to BW consumption.

PMID- 27709827
TI  - [N???I+ ???N] Halogen-Bonded Dimeric Capsules from Tetrakis(3-pyridyl)ethylene
      Cavitands.
AB  - Two [N???I+ ???N] halogen-bonded dimeric capsules using tetrakis(3
      pyridyl)ethylene cavitands with different lower rim alkyl chains are synthesized
      and analyzed in solution and the gas phase. These first examples of symmetrical
      dimeric capsules making use of the iodonium ion (I+ ) as the main connecting
      module are characterized by 1 H NMR spectroscopy, diffusion ordered NMR
      spectroscopy (DOSY), electrospray ionization mass spectrometry (ESI-MS), and ion
      mobility-mass spectrometry (TW-IMS) experiments. The synthesis and effective
      halogen-bonded dimerization proceeds through analogous dimeric capsules with
      [N???Ag+ ???N] binding motifs as the intermediates as evidenced by the X-ray
      structures of (CH2 Cl2 )2 @[3 a2 ?Ag4 ?(H2 O)2 ?OTs4 ] and (CH2 Cl2 )2 @[3 a2
      ?Ag4 ?(H2 O)4 ?OTs4 ], two structurally different capsules.

PMID- 27709828
TI  - Understanding the role of new systemic agents in the treatment of prostate
      cancer.
AB  - OBJECTIVES: To examine the current literature and identify key consensus findings
      from the available studies to better educate urologists and medical oncologists
      on agents used in the treatment of metastatic prostate cancer (mPC). METHODS:
      Following PRISMA guidelines, we conducted a systematic review of the available
      literature on reported trials of systemic therapies for mPC. Two search terms
      were used: 'metastatic prostate cancer' and 'treatment'. RESULTS: A variety of
      agents have demonstrated improved overall survival in patients with mPC. Twenty
      recently documented trials were reported in the literature with a focus on
      enzalutamide, abiraterone acetate, docetaxel and other newer agents. These
      studies were grouped based on patient populations. CONCLUSION: The increasing
      number of high-quality clinical trials, with overlapping patient populations has
      made defining the correct therapy for men with mPC challenging for urologists and
      medical oncologists. The data suggests that the optimal sequence of drugs is not
      only unknown but also not necessarily the same for each patient. As such, we
      suggest a more individualized approach to the treatment of prostate cancer
      depending on patient and disease factors.

PMID- 27709829
TI  - Coronary artery calcification in Korean patients with incident dialysis.
AB  - INTRODUCTION: Patients with chronic kidney disease have an extremely high risk of
      developing cardiovascular disease (CVD). In patients with end-stage renal disease
      (ESRD), coronary artery calcification (CAC) is associated with increased
      mortality from CVD. METHODS: The present study aimed to investigate the risk
      factors for CAC in Korean patients with incident dialysis. Data on 423 patients
      with ESRD who started dialysis therapy between December 2012 and March 2014 were
      obtained from 10 university-affiliated hospitals. CAC was identified by using
      noncontrast-enhanced cardiac multidetector computed tomography. The CAC score was
      calculated according to the Agatston score, with CAC-positive subjects defined by
      an Agatston score >0. FINDINGS: Patients' mean age was 55.6 +/- 14.6 years, and
      64.1% were men. The CAC-positive rate was 63.8% (270 of 423). Results of
      univariate analyses showed significant differences in age, sex, etiology of ESRD
      and comorbid conditions according to the CAC score. However, results of multiple
      regression analysis showed that only a higher age was significantly associated
      with the CAC score. Receiver operating characteristic curves showed that the
      sensitivity and specificity of L-spine radiography for diagnosing CAC were 56%
      and 91%, respectively, for diagnosing CAC (area under the curve, 0.735).
      DISCUSSION: CAC was frequent in patients with incident dialysis, and multiple
      regression analysis showed that only age was significantly associated with the
      CAC score. In addition, L-spine radiography could be a helpful modality for
      diagnosing CAC in patients with incident dialysis.

PMID- 27709830
TI  - A Truncated IL-17RC Peptide Ameliorates Synovitis and Bone Destruction of
      Arthritic Mice.
AB  - Peptide-based therapy, such as modified peptides, has attracted increased
      attention. IL-17 is a promising therapeutic target for autoimmune diseases, and
      levels of circulating bioactive IL-17 are associated with rheumatoid arthritis
      severity. In this study, a modified truncated IL-17RC is generated to ameliorate
      inflammation and bone destruction in arthritis. The truncated IL-17RC binds to
      both IL-17A and IL-17F with higher binding capacity compared to nonmodified IL
      17RC. In addition, the truncated IL-17RC reduces the secretion of inflammatory
      and osteoclastogenic factors induced by IL-17A/F in vitro. Moreover, the
      administration of truncated IL-17RC dramatically improves symptoms of
      inflammation and inhibited bone destruction in collagen-induced arthritis mice.
      Collectively, these data demonstrate that modified truncated IL-17RC peptide may
      be a more effective treatment strategy in the simultaneous inhibition of both IL
      17A and IL-17F signaling, whereas the existing agents neutralize IL-17A or IL-17F
      alone. These suggest that the truncated IL-17RC may be a potential candidate in
      the treatment of inflammatory associated bone diseases.

PMID- 27709831
TI  - GATA binding protein 3 is correlated with leptin regulation of PPARgamma1 in
      hepatic stellate cells.
AB  - Accumulating evidence reveals that hormone leptin, mainly produced by adipocyte,
      plays a unique role in promotion of liver fibrosis. Hepatic stellate cell (HSC)
      activation is a key step in liver fibrosis and peroxisome-proliferator activated
      receptor gamma (PPARgamma) exerts a crucial role in inhibition of HSC activation.
      Our previous researches demonstrated that leptin reduced PPARgamma1 (a major
      subtype of PPARgamma in HSCs) expression through GATA binding protein 2 (GATA2)
      binding to a site around -2323 in PPARgamma1 promoter. The present researches
      aimed to examine the effect of GATA3 on leptin-induced inhibition of PPARgamma1
      and elucidate the relationship between GATA3 and GATA2. Gene expressions were
      analysed by real-time PCR, western blot, luciferase assay and immunostaining.
      C57BL/6J ob/ob mouse model of thioacetamide-induced liver injury was used in
      vivo. Results demonstrate that leptin significantly induces GATA3 expression in
      HSCs by multiple signalling pathways including NADPH oxidase pathway. There exist
      crosstalks between NADPH oxidase pathway and the other pathways. GATA3 can bind
      to GATA2-binding site in PPARgamma1 promoter and interacts with GATA2,
      contributing to leptin inhibition of PPARgamma1 expression in HSCs. These data
      demonstrated novel molecular events for leptin inhibition of PPARgamma1
      expression in HSCs and thus might have potential implications for clarifying the
      detailed mechanisms underlying liver fibrosis in diseases in which circulating
      leptin levels are elevated such as non-alcoholic steatohepatitis in obese
      patients.

PMID- 27709832
TI  - Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications
      in Tissue Engineering, Regenerative Medicine and Immunomodulation.
AB  - As an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi
      faceted role in cell migration, proliferation and differentiation at micro level
      and system level events such as tissue water homeostasis. Among its biological
      functions, it is known to interact with cytokines and contribute to their
      retention in ECM microenvironment. In addition to its biological functions, it
      has advantageous physical properties which result in the industrial endeavors in
      the synthesis and extraction of HA for variety of applications ranging from
      medical to cosmetic. Recently, HA and its derivatives have been the focus of
      active research for applications in biomedical device coatings, drug delivery
      systems and in the form of scaffolds or cell-laden hydrogels for tissue
      engineering. A specific reason for the increase in use of HA based structures is
      their immunomodulatory and regeneration inducing capacities. In this context,
      this article reviews recent literature on modulation of the implantable
      biomaterial microenvironment by systems based on HA and its derivatives,
      particularly hydrogels and microscale coatings that are able to deliver cytokines
      in order to reduce the adverse immune reactions and promote tissue healing.

PMID- 27709833
TI  - Mechanism-Guided Design and Synthesis of a Mitochondria-Targeting Artemisinin
      Analogue with Enhanced Anticancer Activity.
AB  - Understanding the mechanism of action (MOA) of bioactive natural products will
      guide endeavor to improve their cellular activities. Artemisinin and its
      derivatives inhibit cancer cell proliferation, yet with much lower efficiencies
      than their roles in killing malaria parasites. To improve their efficacies on
      cancer cells, we studied the MOA of artemisinin using chemical proteomics and
      found that free heme could directly activate artemisinin. We then designed and
      synthesized a derivative, ART-TPP, which is capable of targeting the drug to
      mitochondria where free heme is synthesized. Remarkably, ART-TPP exerted more
      potent inhibition than its parent compound to cancer cells. A clickable probe ART
      TPP-Alk was also employed to confirm that the attachment of the TPP group could
      label more mitochondrial proteins than that for the ART derivative without TPP
      (AP1). This work shows the importance of MOA study, which enables us to optimize
      the design of natural drug analogues to improve their biological activities.

PMID- 27709834
TI  - 'Compromise position' image alignment to accommodate independent motion of
      multiple clinical target volumes during radiotherapy: A high risk prostate cancer
      example.
AB  - INTRODUCTION: Inclusion of multiple independently moving clinical target volumes
      (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose
      of this research was to use high risk prostate cancer as a clinical example to
      evaluate a 'compromise' image alignment strategy. METHODS: The daily pre
      treatment orthogonal EPI for 14 consecutive patients were included in this
      analysis. Image matching was performed by aligning to the prostate only, the bony
      pelvis only and using the 'compromise' strategy. Residual CTV surrogate
      displacements were quantified for each of the alignment strategies. RESULTS:
      Analysis of the 388 daily fractions indicated surrogate displacements were well
      correlated in all directions (r2  = 0.95 (LR), 0.67 (AP) and 0.59 (SI).
      Differences between the surrogates displacements (95% range) were -0.4 to 1.8 mm
      (LR), -1.2 to 5.2 mm (SI) and -1.2 to 5.2 mm (AP). The distribution of the
      residual displacements was significantly smaller using the 'compromise' strategy,
      compared to the other strategies (p 0.005). The 'compromise' strategy ensured the
      CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations
      when aligned to prostate only. CONCLUSIONS: This study demonstrated the
      feasibility of a compromise position image guidance strategy to accommodate
      simultaneous displacements of two independently moving CTVs. Application of this
      strategy was facilitated by correlation between the CTV displacements and
      resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This
      simple image guidance strategy may also be applicable to other disease sites that
      concurrently irradiate multiple CTVs, such as head and neck, lung and cervix
      cancer.

PMID- 27709835
TI  - Photochemical Molecular Tailoring for Efficient Diffusion and Reorganization of
      Organic Nanocrystals for Ultra-Flexible Organic Semiconductor Arrays.
AB  - Solution-processed organic single crystals with high carrier mobility have been
      actively investigated for diverse applications such as displays, sensors, and
      next generation electronics on a flexible platform. However, the lack of precise
      alignment and growth control of organic single crystals impedes the widespread
      adoption of organic materials in an industrial perspective. Here, a photochemical
      modification approach is reported tailoring the solubility and molecular
      diffusivity of polymeric sacrificial layer and sequential batch-type vapor
      annealing to implement high-performance (average saturation mobility: 8.01 cm2 V
      1 s-1 ) organic single-crystal thin film transistors with large channel width
      including multiple aligned single crystals. Additionally, the mechanical
      properties of the organic single crystals are systematically investigated with
      extreme strain conditions such as bending radius of 150 MUm.

PMID- 27709836
TI  - Rapid and sensitive determination of major polyphenolic components in Euphoria
      longana Lam. seeds using matrix solid-phase dispersion extraction and UHPLC with
      hybrid linear ion trap triple quadrupole mass spectrometry.
AB  - A rapid and sensitive method for the extraction and determination of four major
      polyphenolic components in Euphoria longana Lam. seeds is presented for the first
      time based on matrix solid-phase dispersion extraction followed by ultra high
      performance liquid chromatography with hybrid triple quadrupole linear ion trap
      mass spectrometry. Matrix solid-phase dispersion method was designed for the
      extraction of Euphoria longana seed constituents and compared with microwave
      assisted extraction and ultrasonic-assisted extraction methods. An Ultra high
      performance liquid chromatography with hybrid triple quadrupole linear ion-trap
      mass spectrometry method was developed for quantitative analysis in multiple
      reaction monitoring mode in negative electrospray ionization. The chromatographic
      separation was accomplished using an ACQUITY UPLC BEH C18 (2.1 mm * 50 mm, 1.7
      MUm) column with gradient elution of 0.1% aqueous formic acid and 0.1% formic
      acid in acetonitrile. The developed method was validated with acceptable
      linearity (r2 > 0.999), precision (RSD <= 2.22%) and recovery (RSD <= 2.35%). The
      results indicated that matrix solid-phase dispersion produced comparable
      extraction efficiency compared with other methods nevertheless was more
      convenient and time-saving with reduced requirements on sample and solvent
      volumes. The proposed method is rapid and sensitive in providing a promising
      alternative for extraction and comprehensive determination of active components
      for quality control of Euphoria longana products.

PMID- 27709837
TI  - Development of CAPTSureTM - a new index for the assessment of pediatric
      postthrombotic syndrome.
AB  - : Essentials We developed a discriminative and evaluative index for pediatric
      postthrombotic syndrome (PTS). A Delphi-survey was used for item reduction and
      multi-criteria decision analysis for item weighting. The new index assesses limb
      PTS based on the relative severity of each sign and symptom. Higher scores
      related to higher odds of parental dissatisfaction with their child's condition.
      SUMMARY: Background Postthrombotic syndrome (PTS) is a complication of deep vein
      thrombosis defined by the presence of characteristic signs and symptoms. We
      developed a discriminative and evaluative index for the assessment of upper
      extremity (UE) and lower extremity (LE) pediatric PTS. Methods The items to be
      included in the index were voted for by 26 pediatric thrombosis experts invited
      to participate in a Delphi survey. Subsequent item weighting was based on item
      importance elicited by the use of multicriteria decision analysis (MCDA); 122
      healthcare providers and patients/parents were invited to participate in item
      weighting. The implications of the overall scores were explored by comparison
      with PTS diagnosis (independently assessed by two clinical experts) and parental
      satisfaction/dissatisfaction with their child's current condition. Results Items
      voted for inclusion by at least 70% of the Delphi survey respondents (81%
      response rate) were pain, paresthesia, swelling, heaviness, endurance, collateral
      circulation and arm circumference difference for the UE, and pain, paresthesia,
      swelling, heaviness, tightness, tired limb, redness/purple or blotchy skin,
      endurance, ulcers and thigh/calf circumference difference for the LE. Items were
      then weighted by the use of MCDA (82% response rate). The index had excellent
      discrimination for patients with/without PTS. For every 10-point increase in
      index scores (with higher scores being indicative of worse PTS), the odds of
      parental dissatisfaction increased by 75% and 92% in the UE and LE, respectively.
      Conclusion We report the development of the CAPTSureTM (index for the Clinical
      Assessment of Postthrombotic Syndrome in children), which reflects collective
      judgement of the severity of pediatric PTS. We also provide information on the
      meaning of the scores.

PMID- 27709840
TI  - Expanded 3D Nanofiber Scaffolds: Cell Penetration, Neovascularization, and Host
      Response.
AB  - Herein, a robust method to fabricate expanded nanofiber scaffolds with controlled
      size and thickness using a customized mold during the modified gas-foaming
      process is reported. The expansion of nanofiber membranes is also simulated using
      a computational fluid model. Expanded nanofiber scaffolds implanted
      subcutaneously in rats show cellular infiltration, whereas non-expanded scaffolds
      only have surface cellular attachment. Compared to unexpanded nanofiber
      scaffolds, more CD68+ and CD163+ cells are observed within expanded scaffolds at
      all tested time points post-implantation. More CCR7+ cells appear within expanded
      scaffolds at week 8 post-implantation. In addition, new blood vessels are present
      within the expanded scaffolds at week 2. The formed multinucleated giant cells
      within expanded scaffolds are heterogeneous expressing CD68, CCR7, or CD163
      markers. Together, the present study demonstrates that the expanded nanofiber
      scaffolds promote cellular infiltration/tissue integration, a regenerative
      response, and neovascularization after subcutaneous implantation in rats. The use
      of expanded electrospun nanofiber scaffolds offers a promising method for in situ
      tissue repair/regeneration and generation of 3D tissue models/constructs.

PMID- 27709841
TI  - We Should Not Forget Lessons Learned from the Woo Suk Hwang's Case of Research
      Misconduct and Bioethics Law Violation.

PMID- 27709838
TI  - Time to follow-up of an abnormal mammogram in women with diabetes: a population
      based study.
AB  - Women with diabetes have a higher breast cancer incidence and mortality. They are
      also significantly less likely to undergo screening mammography and present with
      more advanced stage than women without diabetes. The purpose of this study was to
      examine if women with diabetes are more likely to have delays in follow-up of
      abnormal mammograms, compared to women without diabetes. Using population-based
      health databases, this retrospective cohort study examined women between the ages
      of 50 and 74, with and without diabetes, living in the province of Ontario,
      Canada, who underwent screening through a centralized program and who had an
      abnormal mammogram between 2003 and 2012. We compared rates of follow-up of a
      diagnostic test within 180 days, as well as likelihood of mastectomy or excision
      procedure and a diagnosis of breast cancer. Following an abnormal screening
      mammogram, 97.5% of women with diabetes had a diagnostic procedure within 180
      days compared to 97.9% of women without diabetes. After adjustment for other
      factors, women with diabetes were only 3% less likely to have follow-up testing
      after an abnormal mammogram than women without diabetes (hazard ratio [HR] 0.97,
      95% CI: 0.96-0.99, P < 0.001). The majority of Ontario women who underwent
      screening mammography through a centralized screening program had timely follow
      up of an abnormal mammogram, with no meaningful delays in those who had diabetes.
      The results of this study suggest that diagnostic delays after screening do not
      significantly contribute to higher breast cancer mortality in women with
      diabetes.

PMID- 27709843
TI  - The Ecology of Medical Care in Korea.
AB  - This study aimed to describe the ecology of medical care in Korea. Using the
      yearly data of 2012 derived from the Korea Health Panel, we estimated the numbers
      of people per 1,000 residents aged 18 and over who had any health problem and/or
      any medical care at a variety of care settings, such as clinics, hospitals, and
      tertiary hospitals, in an average month. There was a total of 11,518 persons in
      the study population. While the number of those who had any health problem in an
      average month was estimated to be 939 per 1,000 persons, the estimated numbers of
      ambulatory care users were 333 at clinics, 101 at hospital outpatient
      departments, 35 at tertiary hospital outpatient departments, and 38 for Korean
      Oriental medical providers. The number of people who used emergency care at least
      once was 7 per 1,000 persons in an average month. The numbers of people
      hospitalized in clinics and hospitals were 3 and 8, respectively, while 3 persons
      were admitted to tertiary hospitals. There was a gap between the number of people
      experiencing any health problem and that of those having any medical care, and
      primary care comprised a large share of people's medical care experiences. It was
      noteworthy that more patients received ambulatory care at tertiary hospitals in
      Korea than in other countries. We hope that discussion about care delivery system
      reform and further studies will be encouraged.

PMID- 27709842
TI  - Molecular Strain Typing of Mycobacterium tuberculosis: a Review of Frequently
      Used Methods.
AB  - Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, remains one of
      the most serious global health problems. Molecular typing of M. tuberculosis has
      been used for various epidemiologic purposes as well as for clinical management.
      Currently, many techniques are available to type M. tuberculosis. Choosing the
      most appropriate technique in accordance with the existing laboratory conditions
      and the specific features of the geographic region is important. Insertion
      sequence IS6110-based restriction fragment length polymorphism (RFLP) analysis is
      considered the gold standard for the molecular epidemiologic investigations of
      tuberculosis. However, other polymerase chain reaction-based methods such as
      spacer oligonucleotide typing (spoligotyping), which detects 43 spacer sequence
      interspersing direct repeats (DRs) in the genomic DR region; mycobacterial
      interspersed repetitive units-variable number tandem repeats, (MIRU-VNTR), which
      determines the number and size of tandem repetitive DNA sequences; repetitive
      sequence-based PCR (rep-PCR), which provides high-throughput genotypic
      fingerprinting of multiple Mycobacterium species; and the recently developed
      genome-based whole genome sequencing methods demonstrate similar discriminatory
      power and greater convenience. This review focuses on techniques frequently used
      for the molecular typing of M. tuberculosis and discusses their general aspects
      and applications.

PMID- 27709845
TI  - Facing Complaining Customer and Suppressed Emotion at Worksite Related to Sleep
      Disturbance in Korea.
AB  - This study aimed to investigate the effect of facing complaining customer and
      suppressed emotion at worksite on sleep disturbance among working population. We
      enrolled 13,066 paid workers (male = 6,839, female = 6,227, age < 65 years) in
      the 3rd Korean Working Condition Survey (2011). The odds ratio (OR) and 95%
      confidence intervals (CI) for sleep disturbance occurrence were calculated using
      multiple logistic regression models. Among workers in working environments where
      they always engage complaining customers had a significantly higher risk for
      sleep disturbance than rarely group (The OR [95% CI]; 5.46 [3.43-8.68] in male,
      5.59 [3.30-9.46] in female workers). The OR (95% CI) for sleep disturbance was
      1.78 (1.16-2.73) and 1.63 (1.02-2.63), for the male and female groups always
      suppressing their emotions at the workplace compared with those rarely group.
      Compared to those who both rarely engaged complaining customers and rarely
      suppressed their emotions at work, the OR (CI) for sleep disturbance was 9.66
      (4.34-20.80) and 10.17 (4.46-22.07), for men and women always exposed to both
      factors. Sleep disturbance was affected by interactions of both emotional demands
      (engaging complaining customers and suppressing emotions at the workplace). The
      level of emotional demand, including engaging complaining customers and
      suppressing emotions at the workplace is significantly associated with sleep
      disturbance among Korean working population.

PMID- 27709844
TI  - Gender Differences in Sleep Disturbance among Elderly Koreans: Hallym Aging
      Study.
AB  - Sleep is an important component in our lives as it is necessary throughout one's
      entire life span. This study was conducted to elucidate whether there are gender
      differences in sleep quality and what factors can affect sleep quality in
      community-dwelling elderly Koreans. A total of 382 subjects (175 males and 207
      females) were recruited among elderly aged 45 or over who participated in the
      2010 Hallym Aging Study (HAS). They were invited to a general hospital and were
      evaluated for socioeconomic status, smoking history, and various clinical
      measures. Sleep quality was assessed by the Pittsburgh Sleep Quality Index
      (PSQI). A higher score indicates poorer subjective sleep quality, (PSQI global
      score > 5 suggests sleep disturbance). After adjusting for potential covariates,
      our results show that alcohol increases the odds for poor sleep (odds ratio [OR]
      = 3.35, 95% confidence interval [CI] = 1.11-10.10) in males. In females, lack of
      exercise was the major risk factor of poor sleep as they are 4.46 times more
      likely to suffer from low sleep quality than those who exercise regularly (95%
      CI=1.56-13.75). Stress was also a risk factor for poor sleep. It was 5.60 times
      higher in the "always have stress" group than the "do not have stress" group (95%
      CI = 1.54-20.34). Thus, alcohol consumption is associated with men's sleep
      quality, while exercise and stress level affect women's.

PMID- 27709846
TI  - Public Awareness of Stroke and Its Predicting Factors in Korea: a National Public
      Telephone Survey, 2012 and 2014.
AB  - The aim of this study was to investigate time trends in the public awareness of
      stroke and its predicting factors. The target population was 9,600 community
      dwelling adults, aged 19-79 years, in 16 metropolitan cities and provinces in
      Korea. The survey samples in 2012 and 2014 were selected separately (entirely
      different sets of subjects) using a proportionate quota sampling method.
      Information concerning knowledge of stroke and demographics was collected by
      trained telephone interviewers using random digit dialing. After excluding
      subjects with a non-response or refusal to answer any question, the analyses
      included 8,191 subjects in 2012 and 8,127 subjects in 2014. Respondents'
      awareness of stroke warning signs (numbness or weakness, difficulty speaking or
      understanding speech, dizziness, visual impairment, and severe headache) was
      highest for difficulty speaking or understanding speech (80.9% in 2012 and 86.4%
      in 2014). There were significant increases in the proportion of respondents
      understanding the appropriate action (i.e., calling an ambulance) at the time of
      stroke occurrence (59.6% to 67.1%), and in the proportion aware of the general
      need for prompt treatment (86.7% to 89.8%). In multivariable logistic regression
      analysis, older age, higher education level, higher household income, current non
      smoking, exposure to stroke-related public relations materials, and experience of
      stroke education were significantly associated with both high knowledge of stroke
      warning signs and awareness of the need for prompt treatment. Between 2012 and
      2014, the public's awareness of stroke increased significantly. More specialized
      interventions, including public relations materials and education, should focus
      on subgroups who have lower stroke knowledge.

PMID- 27709847
TI  - Risk Factors for the Adverse Events after Conversion from Twice-Daily to Once
      Daily Tacrolimus in Stable Liver Transplantation Patients.
AB  - Despite the therapeutic equivalence between twice-daily and once-daily
      tacrolimus, patient safety after conversion is still a concern. We reviewed 218
      liver transplantation (LT) patients who converted twice-daily to once-daily
      tacrolimus between May 2011 and January 2014. Thirty (13.8%) patients had adverse
      events after conversion, with a liver function test (LFT) abnormality being the
      most common adverse event (n = 17). Despite the decrease in serum tacrolimus of >
      30% after conversion, none of the patients who were converted to a dosage ratio
      (once-daily tacrolimus dosage: twice-daily tacrolimus dosage) > 1 had an LFT
      abnormality. Most patients with an LFT abnormality improved after increasing the
      once-daily tacrolimus dosage (n = 2), returned to a previous medication, and/or
      added another immunosuppressant (n = 15). One patient had acute cellular
      rejection, which improved after steroid pulse treatment, and another patient had
      graft failure. In patients with a dosage ratio <= 1, the conversion time within 5
      years after LT was the only significant risk factor for an LFT abnormality after
      conversion (odds ratio: 11.850, 95% confidence interval: 1.321-106.325, P =
      0.027). In conclusion, the dosage ratio and time after LT should be carefully
      considered during conversion from twice-daily to once-daily tacrolimus.

PMID- 27709848
TI  - Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome
      Coronavirus Infection.
AB  - Clinical progression over time and cytokine profiles have not been well defined
      in patients with Middle East respiratory syndrome coronavirus (MERS-CoV)
      infection. We included 17 patients with laboratory-confirmed MERS-CoV during the
      2015 outbreak in Korea. Clinical and laboratory parameters were collected
      prospectively. Serum cytokine and chemokine levels in serial serum samples were
      measured using enzyme-linked immunosorbent assay. All patients presented with
      fever. The median time to defervescence was 18 days. Nine patients required
      oxygen supplementation and classified into severe group. In the severe group,
      chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea
      developed at the end of the first week and became apparent in the second week.
      Median time from symptom onset to oxygen supplementation was 8 days. The severe
      group had higher neutrophil counts during week 1 than the mild group (4,500 vs.
      2,200/MUL, P = 0.026). In the second week of illness, the severe group had higher
      serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382
      pg/mL, P < 0.001). IFN-alpha response was not observed in mild cases. Our data
      shows that clinical condition may suddenly deteriorate around 7 days of illness
      and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV
      patients who developed severe diseases.

PMID- 27709849
TI  - Neurocognitive Function and Health-Related Quality of Life in Pediatric Korean
      Survivors of Medulloblastoma.
AB  - The neurocognitive function and quality of life of 58 Korean survivors of
      childhood medulloblastoma were assessed after surgery, cranial radiation and
      chemotherapy. All patients were evaluated with a battery of neurocognitive
      function tests and the Pediatric Functional Assessment of Cancer Therapy-Brain
      Tumor Survivors, which consists of self-report questionnaires on quality of life.
      The mean full-scale intelligence quotient (IQ), verbal IQ, and performance IQ
      scores were 90.2, 97.1, and 84.16, respectively. The mean memory quotient (MQ)
      score was 86.78, which was within 1 standard deviation of the average score of
      100. Processing speed, attention, and executive function showed mild to moderate
      deficits. Intelligence, memory, executive function, visuospatial function, and
      simple motor function were significantly lower in the patients diagnosed before 8
      years of age compared with those diagnosed after 8. The cognitive deficits in the
      patients diagnosed at younger ages might be related to earlier exposure to
      craniospinal irradiation and chemotherapy. The patient and parent proxy
      evaluations of attention, fine motor function, and quality of life did not
      differ. We found significant neurocognitive changes in a wide range of
      neurocognitive functional domains in Korean survivors of childhood
      medulloblastoma. Long-term follow-up studies of survivors of childhood
      medulloblastoma beginning at the time of their first diagnosis are required to
      better understand the deficits exhibited by survivors of childhood
      medulloblastoma, so that intervention strategies and treatment refinements that
      reduce the long-term neurocognitive decline can be developed.

PMID- 27709851
TI  - Comparison of Dosimetric Performance among Commercial Quality Assurance Systems
      for Verifying Pretreatment Plans of Stereotactic Body Radiotherapy Using
      Flattening-Filter-Free Beams.
AB  - The purpose of this study was to compare the performance of different commercial
      quality assurance (QA) systems for the pretreatment verification plan of
      stereotactic body radiotherapy (SBRT) with volumetric arc therapy (VMAT)
      technique using a flattening-filter-free beam. The verification for 20
      pretreatment cancer patients (seven lung, six spine, and seven prostate cancers)
      were tested using three QA systems (EBT3 film, I'mRT MatriXX array, and
      MapCHECK). All the SBRT-VMAT plans were optimized in the Eclipse (version
      11.0.34) treatment planning system (TPS) using the Acuros XB dose calculation
      algorithm and were delivered to the Varian TrueBeam(r) accelerator equipped with
      a high-definition multileaf collimator. Gamma agreement evaluation was analyzed
      with the criteria of 2% dose difference and 2 mm distance to agreement (2%/2 mm)
      or 3%/3 mm. The highest passing rate (99.1% for 3%/3 mm) was observed on the
      MapCHECK system while the lowest passing rate was obtained on the film. The
      pretreatment verification results depend on the QA systems, treatment sites, and
      delivery beam energies. However, the delivery QA results for all QA systems based
      on the TPS calculation showed a good agreement of more than 90% for both the
      criteria. It is concluded that the three 2D QA systems have sufficient potential
      for pretreatment verification of the SBRT-VMAT plan.

PMID- 27709852
TI  - Natural Course of Adult Ebstein Anomaly When Treated according to Current
      Recommendation.
AB  - The objectives of this study were to assess the clinical outcomes of adults with
      Ebstein Anomaly (EA) according to their treatment modalities. All adult EA
      patients diagnosed between October 1994 and October 2014 were retrospectively
      evaluated by medical record review. Total 60 patients were categorized into 3
      groups according to their treatment strategy, i.e. non-operative treatment (Group
      I, n = 23), immediate operative treatment (Group II, n = 27), and delayed
      operative treatment (Group III, n = 10). A composite of major adverse cardiac and
      cerebrovascular events (MACCE) and factors associated with MACCE were assessed in
      each treatment group. MACCE occurred in 13.0% patients in Group I, 55.6% patients
      in Group II and 50% in Group III (P = 0.006). Event free survivals at 5 years
      were 90% in Group I, 52.7% in Group II, 50.0% in Group III (P = 0.036). Post
      operatively, most patients showed improvement on clinical symptoms. However,
      event free survival rate was lower in patients with operation compared to those
      with non-operative treatment (58.7% vs. 90.9%; P = 0.007). Major arrhythmic event
      occurred more frequently even after surgical ablation (50.0% vs. 20.0%; P =
      0.034). Re-operation was more frequent in patients underwent delayed surgery
      compared to those with immediate surgery (50.0% vs. 18.5%; P = 0.001). Current
      guideline to decide patient's treatment strategy appeared to be appropriate in
      adult patients with EA. However, surgical ablation for arrhythmia was not enough
      so that concomitant medical treatment should be considered. Therefore, attentive
      risk stratification and cautious decision of treatment strategy by experienced
      cardiac surgeon are believed to improve clinical outcome.

PMID- 27709850
TI  - The Different Effect of VEGF Polymorphisms on the Prognosis of Non-Small Cell
      Lung Cancer according to Tumor Histology.
AB  - Vascular endothelial growth factor (VEGF) contributes to tumor angiogenesis. The
      role of VEGF single nucleotide polymorphisms (SNPs) in lung cancer susceptibility
      and its prognosis remains inconclusive and controversial. This study was
      performed to investigate whether VEGF polymorphisms affect survival outcomes of
      patients with early stage non-small cell lung cancer (NSCLC) after surgery. Three
      potentially functional VEGF SNPs (rs833061T>C, rs2010963G>C, and rs3025039C>T)
      were genotyped. A total of 782 NSCLC patients who were treated with surgical
      resection were enrolled. The association of the SNPs with overall survival (OS)
      and disease free survival (DFS) was analyzed. In overall population, none of the
      three polymorphisms were significantly associated with OS or DFS. However, when
      the patients were stratified by tumor histology, squamous cell carcinoma (SCC)
      and adenocarcinoma (AC) had significantly different OS (Adjusted hazard ratio
      [aHR] = 0.76, 95% CI = 0.56-1.03 in SCC; aHR = 1.33, 95% CI = 0.98-1.82 in AC; P
      for heterogeneity = 0.01) and DFS (aHR = 0.75, 95% CI = 0.58-0.97 in SCC; aHR =
      1.26, 95% CI = 1.00-1.60 in AC; P for heterogeneity = 0.004) according to the
      rs833061T>C genotypes. Our results suggest that the prognostic role of VEGF
      rs833061T>C may differ depending on tumor histology.

PMID- 27709853
TI  - Clinical Characteristics and Treatment Outcomes of Primary Pulmonary Artery
      Sarcoma in Korea.
AB  - Pulmonary artery sarcomas (PAS) are rare malignant neoplasms. Right heart failure
      due to tumour location is the main cause of death in PAS patients. The
      hemodynamic influence of PAS may effect prognosis, but this has not been proven.
      We aimed to identify the clinical characteristics and prognostic factors of PAS
      in Korea, their association with pulmonary hypertension (PH). PAS patients
      treated at the Asan Medical Center between 2000 and 2014 were reviewed. We
      examined demographic characteristics, diagnostic and treatment modalities.
      Potential prognostic factors were evaluated by univariate and multivariate
      analysis. Twenty patients were diagnosed with PAS. Ten patients were male, the
      median age was 54 years (range, 33-75 years). The most common symptom observed
      was dyspnea (65%). The most common histologic type was spindle cell sarcoma
      (30%). Ten patients had a presumptive diagnosis of pulmonary embolism (PE) and
      received anticoagulation therapy. Seventeen patients underwent surgery, but only
      5 patients had complete resection. Eleven patients received post-operative
      treatment (chemotherapy = 3, radiotherapy = 5, chemoradiotherapy = 3). PH was
      observed in 12 patients before treatment and in 6 patients after treatment.
      Overall median survival was 24 months. Post-treatment PH was associated with poor
      prognosis (HR 9.501, 95% CI 1.79-50.32; P = 0.008) while chemotherapy was
      negatively associated with mortality (HR 0.102, 95% CI 0.013-0.826; P = 0.032) in
      univariate analysis. Post-treatment PH was also associated with poor prognosis in
      multivariate analysis (HR 5.7, 95% CI 1.08-30.91; P = 0.041). PAS patients are
      frequently misdiagnosed with PE in Korea. Post-treatment PH is associated with a
      poor prognosis.

PMID- 27709854
TI  - The Risk for Insulin Resistance according to the Degree of Non-Alcoholic Fatty
      Liver Disease in Korean Men.
AB  - Insulin resistance (IR) plays a significant role in the development and
      progression of non-alcoholic fatty liver disease (NAFLD). However, the natural
      course of insulin sensitivity under NAFLD remained unclear. Accordingly, this
      study was designed to investigate the effect of NAFLD on insulin resistance. A
      total of 20,628 Korean men without homeostasis model assessment of insulin
      resistance (HOMA-IR < 2.7) were followed-up for 5 years. They were serially
      checked for HOMA-IR to monitor the development of IR (HOMA-IR >= 2.7). The
      incidence rate of IR increased according to the degree of NAFLD (normal: 11.6%,
      mild: 28.8%, moderate to severe: 40.5%, P < 0.001). Cox proportional hazards
      model showed that HRs (95% CI) for IR increased proportionally to the degree of
      NAFLD (mild: 1.19 [1.02-1.39], moderate to severe: 1.32 [1.08-1.57]). IR was more
      potentially associated with the more progressive NAFLD than normal and milder
      state. In addition, NAFLD was the independent risk factor of the development of
      IR. These results suggest the potential availability of NAFLD as a predictor of
      IR.

PMID- 27709855
TI  - Using Forceps Biopsy after Small Submucosal Dissection in the Diagnosis of
      Gastric Subepithelial Tumors.
AB  - The current tissue sampling techniques for subepithelial tumors (SETs) of the
      gastrointestinal (GI) tract have limited diagnostic efficacy. We evaluated the
      diagnostic yield and safety of forceps biopsies after small endoscopic submucosal
      dissection (SESD biopsies) in the diagnosis of gastric SETs. A total of 42
      patients with gastric SETs > 10 mm were prospectively enrolled between May 2013
      and October 2014. A dual knife was used to incise the mucosa and submucosa and
      forceps biopsies were then introduced deep into the lesion. To compare SESD
      biopsies with EUS-FNA, we used the retrospective data of 30 EUS-FNA cases. The
      diagnostic yield of SESD biopsies was comparable to that of EUS-FNA (35/42, 83.3%
      vs. 24/30, 80.0%, P = 0.717). The mean procedure time of SESD biopsies was
      shorter than that of EUS-FNA (10 vs. 37 minutes, P < 0.001). There were no
      procedure-related adverse events in the both group. The pathological diagnoses in
      SESD biopsies group included 15 leiomyomas, 7 GISTs, 10 heterotopic pancreases, 2
      lipomas, and one other lesion. SESD biopsies are an easy, effective and safe
      technique for the diagnosis of gastric SETs and its diagnostic yield is
      comparable to that of EUS-FNA. This technique may be a reliable alternative to
      conventional EUS-FNA (Clinical trial registration No. KCT0000730).

PMID- 27709856
TI  - The Experience of Human Milk Banking for 8 Years: Korean Perspective.
AB  - Human milk banks are a solution for mothers who cannot supply their own breast
      milk to their sick or hospitalized infants; premature infants, in particular, are
      unable to receive a full volume of breast milk for numerous reasons. As of
      December 2015, there was only one milk bank in a university hospital in Korea. We
      reviewed the basic characteristics of donors and recipients, and the amounts and
      contamination of breast milk donated at the Human Milk Bank in Kyung Hee
      University Hospital at Gangdong in Korea from 2008 to 2015. The donor pool
      consisted of 463 first-time donors and 452 repeat donors who made 1,724
      donations. A total of 10,820 L of breast milk was collected, and 9,541.6 L were
      processed. Detectable bacteria grew in 12.6% after pasteurization and 52.5% had
      cytomegalovirus DNA before pasteurization in donated milk. There were 836 infant
      and 25 adult recipients; among new infant recipients, 48.5% were preterm; the
      groups received 8,009 and 165.7 L of donor milk, respectively. There was an
      increase in the percentage of preterm infants among new infant recipients in 2015
      (93.1%) compared to 2008 (8.5%). Based on the number of premature infants in
      Korea, the number of potential recipients is not likely to diminish anytime soon,
      despite efforts to improve the breastfeeding rate. Sustainability and quality
      improvement of the milk bank need long-term financial support by health
      authorities and a nationwide network similar to blood banking will further
      contribute to the progress of milk banking.

PMID- 27709857
TI  - Distribution of Diseases Causing Liver Function Test Abnormality in Children and
      Natural Recovery Time of the Abnormal Liver Function.
AB  - Although liver function test abnormality is frequently noted in children, there
      is no report about the distribution of the etiology and natural recovery time of
      the abnormal liver function. From March 2005 to February 2014, clinical
      information was retrospectively collected from 559 children who had abnormal
      liver function and were hospitalized or visited the outpatient clinic at the Jeju
      National University Hospital. The etiology of abnormal liver function was
      classified into groups and the natural recovery time of abnormal liver function
      was analyzed. The etiological groups of 559 patients included 'nonspecific
      hepatitis' in 42 (7.5%), 'infection' in 323 (57.8%), 'rheumatologic and
      autoimmune' in 66 (11.8%), 'nonalcoholic fatty liver disease' in 57 (10.2%),
      'anatomic' in 12 (2.1%), 'toxic' in 13 (2.1%), 'metabolic' in 8 (1.4%),
      'hematologic' in 7 (1.3%), 'hemodynamic' in 4 (0.7%), and 'others' in 27 (4.8%).
      Among the 'infection' group (57.8%), the 'viral infection in the respiratory
      tract' subgroup, which had 111 patients (19.8%), was the most common. The natural
      recovery time of the abnormal liver function was 27 days (median) in 'nonspecific
      hepatitis', 13 days (median) in 'viral respiratory tract disease', 16 days
      (median) in 'viral gastroenteritis', 42 days (median) in 'viral febrile illness",
      and 7 days (median) in "Kawasaki disease". The information on the natural
      recovery time of abnormal liver function may help the physician to perform good
      clinical consultation for patients and their parents.

PMID- 27709858
TI  - Prevalence of Low Bone Mineral Density and Associated Risk Factors in Korean
      Puerperal Women.
AB  - Although pregnancy is a medical condition that contributes to bone loss, little
      information is available regarding bone mineral density (BMD) in puerperal women.
      This cross sectional study aimed to evaluate the prevalence of low BMD in
      puerperal women and to identify associated risk factors. We surveyed all
      puerperal women who had BMD measurements taken 4-6 weeks after delivery in a
      tertiary university hospital, and did not have any bone loss-related
      comorbidities. Among the 1,561 Korean puerperal women, 566 (36.3%) had low BMD at
      the lumbar spine, total hip, femoral neck, and/or trochanter. Multivariate
      analysis revealed that underweight women had a significantly higher risk of low
      BMD compared with obese women at pre-pregnancy (adjusted odds ratio [aOR], 3.21;
      95% confidence interval [CI], 1.83-5.63). Also, women with inadequate gestational
      weight gain (GWG) were 1.4 times more likely to have low BMD than women with
      excessive GWG (aOR, 1.42; 95% CI, 1.04-1.94). One-way ANOVA showed that BMDs at
      the lumbar spine and total hip were significantly different between the 4 BMI
      groups (both P < 0.001) and also between the 3 GWG groups (both P < 0.001). In
      conclusion, this study identifies a high prevalence of low BMD in puerperal women
      and thus suggests the need for further evaluation about the change of BMD in
      pregnancy and postpartum period.

PMID- 27709859
TI  - Seasonal Pattern of Preterm Births in Korea for 2000-2012.
AB  - The aim of this study was to investigate a seasonal pattern of preterm births in
      Korea. Data were obtained from the national birth registry of the Korean
      Statistics Office and included all births in Korea during the period 2000-2012 (n
      = 6,310,800). Delivery dates were grouped by month of the year or by season
      (winter [December, January, February], spring [March, April, May], summer [June,
      July, August], and autumn [September, October, November]). The seasonal patterns
      of prevalence of preterm births were assessed. The rates of preterm births at 37
      weeks were highest twice a year (once in winter and again in summer). The rates
      of preterm births increased by 13.9% in summer and 7.5% in winter, respectively,
      than in spring (OR, 1.139; 95% CI, 1.127-1.152, and OR, 1.075; 95% 1.064-1.087,
      respectively) after controlling for age, the educational level of the parents,
      maternal parity, and neonatal gender. The pattern for spontaneous preterm births
      < 34 weeks was similar. In Korea, a seasonal pattern of preterm births was
      observed, with peak prevalence in summer and winter. A seasonal pattern of
      preterm births may provide new insights for the pathophysiology of preterm
      births.

PMID- 27709860
TI  - Cause of Death in Korean Men with Prostate Cancer: an Analysis of Time Trends in
      a Nationwide Cohort.
AB  - Despite rapid increase in incidence of prostate cancer (PC) and PC survivors,
      there are few studies regarding competing causes of death and time trends in
      Asian population. We conducted a cohort study of 2% nationwide random sample of
      Korean National Health Insurance employees. A total of 873 patients who had
      received active treatments, including surgery, radiation therapy (RT) and
      androgen deprivation therapy (ADT), for newly diagnosed PC between 2003 and 2010
      were included. The cause of death was categorized as PC, other cancers,
      cardiovascular disease, and other causes. During a median follow-up of 4.75
      years, 29.4% (257/873) of the study population died. PC, other cancers,
      cardiovascular disease, and other causes were responsible for 46.3%, 35.4%, 6.6%,
      and 11.7%, respectively, of the decedents. Significant differences existed in the
      cause of death among treatment groups (P < 0.001). Only 20% and 9.5% of surgery
      and RT group died of PC, whereas 63.9% of ADT group died of PC. Other cancers
      were responsible for 56%, 74.6% and 17.8% of death in the surgery, RT and ADT
      group, respectively, while cardiovascular disease accounted for 4%, 6.3%, and
      7.1% of death in the treatment groups. Analysis of time trends showed that PC
      specific death tended to decrease (from 42.9% in 2003 to 23.1% in 2010), whereas
      non-PC causes tended to increase over the 8 years. Our results are valuable in
      overviewing causes of death and time trends in Korean PC patients, and planning
      future health policy for PC.

PMID- 27709861
TI  - Risk Factor Analysis of Ciprofloxacin-Resistant and Extended Spectrum Beta
      Lactamases Pathogen-Induced Acute Bacterial Prostatitis in Korea.
AB  - The objectives of this study were to investigate risk factors and the incidence
      of ciprofloxacin resistance and extended-spectrum beta-lactamases (ESBL) in
      patients with acute bacterial prostatitis (ABP). We reviewed the medical records
      of 307 patients who were diagnosed with ABP between January 2006 and December
      2015. The etiologic pathogens and risk factors for ciprofloxacin-resistant E.
      coli and ESBL-producing microbes, susceptibility to ciprofloxacin, and the
      incidence of ESBL in patients with ABP were described. History of prior urologic
      manipulation was an independent risk factor for ciprofloxacin-resistant (P =
      0.005) and ESBL-producing microbes (P = 0.005). Advanced age (over 60 years) was
      an independent risk factor for ciprofloxacin-resistant microbes (P = 0.022). The
      ciprofloxacin susceptibility for Escherichia coli in groups without prior
      manipulation was documented 85.7%. For groups with prior manipulation, the
      susceptibility was 10.0%. Incidence of ESBL-producing microbes by pathogen was
      3.8% for E. coli and 1.0% for Klebsiella pneumonia in the absence of manipulation
      group, and 20% and 33.3% in the presence of manipulation group, respectively.
      Initial treatment of ABP must consider patient's age and the possibility of prior
      manipulation to optimize patient treatment. With the high rate of resistance to
      fluoroquinolone, cephalosporins with amikacin, or carbapenems, or extended
      spectrum penicillin with beta lactamase inhibitor should be considered as the
      preferred empirical ABP treatment in the patients with history of prior urologic
      manipulation.

PMID- 27709862
TI  - Association of Overweight with the Prevalence of Lifetime Psychiatric Disorders
      and Suicidality: General Population-based Study in Korea.
AB  - Many epidemiological studies suggest that overweight is associated with an
      elevated risk of psychiatric disorders and suicidal tendency. However, findings
      vary across studies, and some have contradictory results. We investigated the
      relationship of overweight with a range of psychiatric disorders and suicidality
      in the Korean general population. A multistage cluster sampling design was
      adopted. A total of 6,022 participants aged 18-74 years completed face-to-face
      interviews (response rate: 78.7%) including assessment of psychiatric disorders,
      suicidality, and height and weight. Overweight (defined as body mass index of >=
      25) was associated with an increase in the lifetime prevalence of depressive
      disorders (adjusted odds ratio [AOR] 1.38; 95% confidence interval [CI], 1.07
      1.77), suicidal ideation (AOR, 1.42; 95% CI, 1.20-1.68), and suicidal plans (AOR,
      1.44; 95% CI, 1.02-2.03), controlling for sociodemographic variables. Subgroup
      analysis found that the association between overweight and depressive disorders
      exists only in women aged 18-44 years (AOR, 1.75; 95% CI, 1.07-2.89) while the
      association of overweight with suicidal ideation (AOR, 2.08; 95% CI, 1.53-2.82)
      and suicide plans (AOR, 2.59; 95% CI, 1.25-5.37) existed only in men aged 18-44
      years. Overweight was associated with increased odds of nicotine use disorders in
      women aged 18-44 years (AOR, 2.35; 95% CI, 1.02-5.43), but the association was in
      the opposite direction in men aged 45-74 years (AOR, 0.64; 95% CI, 0.43-0.94). In
      conclusion, overweight is related to various psychiatric disorders and
      suicidality in Korea. Policy makers and clinicians should pay more attention to
      the mental health of overweight individuals.

PMID- 27709863
TI  - Intra-Articular Injections in Patients with Femoroacetabular Impingement: a
      Prospective, Randomized, Double-blind, Cross-over Study.
AB  - We evaluated and compared the effectiveness of intra-articular injection of hip
      joint using hyaluronic acid and steroid in patients with femoroacetabular
      impingement (FAI). Thirty patients with FAI clinically and radiologically were
      enrolled and underwent hip injection using steroid (TA) or hyaluronic acid (HA)
      at 0-weeks with cross-over injection at 2-weeks in patients without clinical
      response of decrease of pain intensity less than 2-point. Patients were followed
      up to 12-weeks for pain intensity (Numeric rating scale, NRS: 0-10), hip
      disability score (HOOS), oral medication and adverse events. In 17 patients
      without cross-over, HOOS at 2-weeks was improved significantly in patients with
      HA injection (mean increase of HOOS = 13.8 with HA vs. -2.2 with TA, P = 0.031)
      without difference of NRS (P = 0.943). In 13 patients with cross-over, NRS was
      significantly improved at 2-weeks with first TA injection (mean decrease of NRS=
      1.7 with first TA vs. 0.3 with first HA, P = 0.036), without difference of HOOS
      (P = 0.431). At 4-weeks, NRS and HOOS were significantly different according to
      injection drugs (NRS: 0.9 with TA first and HA later vs. 2.7 with HA first and TA
      later, P = 0.001; mean increase of HOOS: 5.3 with TA first and HA later vs. 10.2
      with HA first and TA later, P = 0.032). Intra-articular hip injection may be
      effective in FAI, with faster effect of pain improvement by TA and more delayed
      effect of function improvement by HA.

PMID- 27709864
TI  - Pharmacological and Mechanical Thromboprophylaxis in Critically Ill Patients: a
      Network Meta-Analysis of 12 Trials.
AB  - Thromboprophylaxis for venous thromboembolism is widely used in critically ill
      patients. However, only limited evidence exists regarding the efficacy and safety
      of the various thromboprophylaxis techniques, especially mechanical
      thromboprophylaxis. Therefore, we performed meta-analysis of randomized
      controlled trials (RCTs) that compared the overall incidence of deep vein
      thrombosis (DVT) for between unfractionated heparin (UFH), low-molecular-weight
      heparin (LMWH), and intermittent pneumatic compression (IPC) in critically ill
      patients. A Bayesian random effects model for multiple treatment comparisons was
      constructed. The primary outcome measure was the overall incidence of DVT at the
      longest follow-up. The secondary outcome measure was the incidence of major
      bleeding, as defined by the original trials. Our analysis included 8,622 patients
      from 12 RCTs. The incidence of DVT was significantly lower in patients treated
      with UFH (OR, 0.45; 95% CrI, 0.22-0.83) or LMWH (OR, 0.38; 95% CrI, 0.18-0.72)
      than in patients in the control group. IPC was associated with a reduced
      incidence of DVT compared to the control group, but the effect was not
      statistically significant (OR, 0.50; 95% CrI, 0.20-1.23). The risk of DVT was
      similar for patients treated with UFH and LMWH (OR, 1.16; 95% CrI, 0.68-2.11).
      The risk of major bleeding was similar between the treatment groups in medical
      critically ill patients and also in critically ill patients with a high risk of
      bleeding. In critically ill patients, the efficacy of mechanical
      thromboprophylaxis in reducing the risk of DVT is not as robust as those of
      pharmacological thromboprophylaxis.

PMID- 27709865
TI  - Performance Evaluation of Five Different Disseminated Intravascular Coagulation
      (DIC) Diagnostic Criteria for Predicting Mortality in Patients with Complicated
      Sepsis.
AB  - Disseminated intravascular coagulation (DIC) is a major complication in sepsis
      patients. We compared the performance of five DIC diagnostic criteria, focusing
      on the prediction of mortality. One hundred patients with severe sepsis or septic
      shock admitted to intensive care unit (ICU) were enrolled. Routine DIC laboratory
      tests were performed over the first 4 days after admission. The overall ICU and
      28-day mortality in DIC patients diagnosed from five criteria (International
      Society on Thrombosis and Haemostasis [ISTH], the Japanese Association for Acute
      Medicine [JAAM], the revised JAAM [R-JAAM], the Japanese Ministry of Health and
      Welfare [JMHW] and the Korean Society on Thrombosis and Hemostasis [KSTH]) were
      compared. Both KSTH and JMHW criteria showed superior performance than ISTH, JAAM
      and R-JAAM criteria in the prediction of overall ICU mortality in DIC patients
      (odds ratio 3.828 and 5.181, P = 0.018 and 0.006, 95% confidence interval 1.256
      11.667 and 1.622-16.554, respectively) when applied at day 1 after admission, and
      survival analysis demonstrated significant prognostic impact of KSTH and JMHW
      criteria on the prediction of 28-day mortality (P = 0.007 and 0.049,
      respectively) when applied at day 1 after admission. In conclusion, both KSTH and
      JMHW criteria would be more useful than other three criteria in predicting
      prognosis in DIC patients with severe sepsis or septic shock.

PMID- 27709866
TI  - Relapsing Polychondritis with Central Nervous System Involvement: Experience of
      Three Different Cases in a Single Center.
AB  - Relapsing polychondritis (RP) is an autoimmune disorder characterized by
      inflammation in cartilaginous structures including the ears, noses, peripheral
      joints, and tracheobronchial tree. It rarely involves the central nervous system
      (CNS) but diagnosis of CNS complication of RP is challenging because it can
      present with varying clinical features. Herein we report 3 cases of relapsing
      polychondritis involving CNS with distinct manifestations and clinical courses.
      The first patient presented with rhombencephalitis resulting in brain edema and
      death. The second patient had acute cognitive dysfunction due to limbic
      encephalitis. He was treated with steroid pulse therapy and recovered without
      sequelae. The third patient suffered aseptic meningitis that presented as
      dementia, which was refractory to steroid and immune suppressive agents. We also
      reviewed literature on CNS complications of RP.

PMID- 27709867
TI  - Letter to the Editor: Compression Rate during Cardiopulmonary Resuscitation.

PMID- 27709868
TI  - The Author's Response: Compression Rate during Cardiopulmonary Resuscitation.

PMID- 27709869
TI  - Erratum: Correction of Figure: Simvastatin Reduces Capsular Fibrosis around
      Silicone Implants.
AB  - This corrects the article on p. 1273 in vol. 31, PMID: 27478339.

PMID- 27709877
TI  - Polymer Brushes for Membrane Separations: A Review.
AB  - The fundamentals and applications of polymer brush-modified membranes are
      reviewed. This new class of synthetic membranes is explored with an emphasis on
      tuning the membrane performance through polymer brush grafting. This work
      highlights the intriguing performance characteristics of polymer brush-modified
      membranes in a variety of separations. Polymer brushes are a versatile and
      effective means in designing membranes for applications in protein adsorption and
      purification, colloid stabilization, sensors, water purification, pervaporation
      of organic compounds, gas separations, and as stimuli responsive materials.

PMID- 27709878
TI  - Coherent-Interface-Assembled Ag2O-Anchored Nanofibrillated Cellulose Porous
      Aerogels for Radioactive Iodine Capture.
AB  - Nanofibrillated cellulose (NFC) has received increasing attention in science and
      technology because of not only the availability of large amounts of cellulose in
      nature but also its unique structural and physical features. These high-aspect
      ratio nanofibers have potential applications in water remediation and as a
      reinforcing scaffold in composites, coatings, and porous materials because of
      their fascinating properties. In this work, highly porous NFC aerogels were
      prepared based on tert-butanol freeze-drying of ultrasonically isolated bamboo
      NFC with 20-80 nm diameters. Then nonagglomerated 2-20-nm-diameter silver oxide
      (Ag2O) nanoparticles (NPs) were grown firmly onto the NFC scaffold with a high
      loading content of ~500 wt % to fabricate Ag2O@NFC organic-inorganic composite
      aerogels (Ag2O@NFC). For the first time, the coherent interface and interaction
      mechanism between the cellulose Ibeta nanofiber and Ag2O NPs are explored by high
      resolution transmission electron microscopy and 3D electron tomography.
      Specifically, a strong hydrogen between Ag2O and NFC makes them grow together
      firmly along a coherent interface, where good lattice matching between specific
      crystal planes of Ag2O and NFC results in very small interfacial straining. The
      resulting Ag2O@NFC aerogels take full advantage of the properties of the 3D
      organic aerogel framework and inorganic NPs, such as large surface area,
      interconnected porous structures, and supreme mechanical properties. They open up
      a wide horizon for functional practical usage, for example, as a flexible
      superefficient adsorbent to capture I- ions from contaminated water and trap I2
      vapor for safe disposal, as presented in this work. The viable binding mode
      between many types of inorganic NPs and organic NFC established here highlights
      new ways to investigate cellulose-based functional nanocomposites.

PMID- 27709879
TI  - Real-Time Profiling of Solid-State Nanopores During Solution-Phase
      Nanofabrication.
AB  - We describe a method for simply characterizing the size and shape of a nanopore
      during solution-based fabrication and surface modification, using only low
      overhead approaches native to conventional nanopore measurements. Solution-based
      nanopore fabrication methods are democratizing nanopore science by supplanting
      the traditional use of charged-particle microscopes for fabrication, but nanopore
      profiling has customarily depended on microscopic examination. Our approach
      exploits the dependence of nanopore conductance in solution on nanopore size,
      shape, and surface chemistry in order to characterize nanopores. Measurements of
      the changing nanopore conductance during formation by etching or deposition can
      be analyzed using our method to characterize the nascent nanopore size and shape,
      beyond the typical cylindrical approximation, in real-time. Our approach thus
      accords with ongoing efforts to broaden the accessibility of nanopore science
      from fabrication through use: it is compatible with conventional instrumentation
      and offers straightforward nanoscale characterization of the core tool of the
      field.

PMID- 27709881
TI  - Facile Synthesis of Ge/N-Doped Carbon Spheres with Varying Nitrogen Content for
      Lithium Ion Battery Anodes.
AB  - The simple fabrication of composites of germanium nanoparticles dispersed on
      nitrogen-doped carbon nanospheres (Ge/NC) of varying nitrogen content and their
      performance in lithium ion battery anodes are reported. A heavily nitrogen-doped
      carbon gel was formed by condensing m-phenylenediamine with formaldehyde (PF
      gel); a less heavily N-doped gel was formed by condensing resorcinol and m
      phenylenediamine with formaldehyde (RPF-gel); and an undoped gel was formed by
      condensing resorcinol with formaldehyde (RF-gel). Pyrolises of the gels with
      GeCl4 at 750  degrees C produced nanocrystalline Ge composites with 7.5 atom % N
      doped carbon, termed Ge/NC (PF), with 3.9% N-doped carbon, termed Ge/NC (RPF) and
      undoped carbon, termed Ge/C (RF). The heavily N-doped Ge/NC (PF) anode retained a
      reversible capacity of 684 mAhg-1 at a specific current of 0.2 Ag-1 after 200
      cycles, versus 337 mAhg-1 retained by anode made with Ge/NC (RPF) and 278 mAhg-1
      retained by anode made with undoped Ge/C (RF). At a specific current 2.0 Ag-1,
      the capacity of the Ge/NC (PF) anode was 472 mAhg-1, versus the 210 mAhg-1 of the
      Ge/NC (RPF) anode and 83 mAhg-1 of the Ge/C (RF) anode. The enhanced performance
      of the Ge/NC (PF) anode is attributed to the better electrical conductivity of
      Ge/NC (PF) and to the higher density of Li+ binding defects in its N-doped
      carbon.

PMID- 27709880
TI  - TEMPO-Oxidized Nanocellulose Fiber-Directed Stable Aqueous Suspension of
      Plasmonic Flower-like Silver Nanoconstructs for Ultra-Trace Detection of
      Analytes.
AB  - The synthesis of shape-tuned silver (Ag) nanostructures with high plasmon
      characteristics has become of significant importance in in vitro diagnostic
      applications. Herein, we report a simple aqueous synthetic route using 2,2,6,6
      tetramethylpiperidine-1-oxyl-oxidized nanocellulose fibers (T-NCFs) and trisodium
      citrate (TSC) that results in anisotropically grown flower-like Ag nanoconstructs
      (AgNFs). A detailed investigation of the concentration and sequence of the
      addition of reactants in the formation of these anisotropic Ag structures is
      presented. Our experimental results show that the mechanism underlying the
      formation of AgNFs is facilitated by the synergistic action of T-NCFs and TSC on
      the directional growth of Ag nuclei during the primary stage, which later develop
      into a flower-like structure by the ripening of larger particles consuming
      smaller Ag particles. As a result the final structure comprises flower-like
      morphology over which several smaller Ag particles (of size <10 nm) are adhered.
      The aqueous AgNF colloid exhibits high stability (zeta = -69.4 mV) and long shelf
      life at neutral pH (>4 months) by the efficient capping action of T-NCFs.
      Further, an as-synthesized nanoconstructs shows excellent surface-enhanced Raman
      scattering activity, which enables ultrasensitive detection of p-aminothiophenol
      with a concentration down to 10 aM (10-17 M) in a reproducible way. This
      biosupported synthesis of stable aqueous colloids of AgNF may find potential
      applications as a biomedical sensing platform for the trace level detection of
      analyte molecules.

PMID- 27709882
TI  - n-MoS2/p-Si Solar Cells with Al2O3 Passivation for Enhanced Photogeneration.
AB  - Molybdenum disulfide (MoS2) has recently emerged as a promising candidate for
      fabricating ultrathin-film photovoltaic devices. These devices exhibit excellent
      photovoltaic performance, superior flexibility, and low production cost. Layered
      MoS2 deposited on p-Si establishes a built-in electric field at MoS2/Si interface
      that helps in photogenerated carrier separation for photovoltaic operation. We
      propose an Al2O3-based passivation at the MoS2 surface to improve the
      photovoltaic performance of bulklike MoS2/Si solar cells. Interestingly, it was
      observed that Al2O3 passivation enhances the built-in field by reduction of
      interface trap density at surface. Our device exhibits an improved power
      conversion efficiency (PCE) of 5.6%, which to our knowledge is the highest
      efficiency among all bulklike MoS2-based photovoltaic cells. The demonstrated
      results hold the promise for integration of bulklike MoS2 films with Si-based
      electronics to develop highly efficient photovoltaic cells.

PMID- 27709884
TI  - Black Phosphorus Nanoparticle Labels for Immunoassays via Hydrogen Evolution
      Reaction Mediation.
AB  - Black phosphorus is an emerging layered material. Its nanoparticles show an
      increased bandgap when compared to bulk materials and they are typically
      fabricated by ultrasonication of macroscopic black phosphorus crystals. Here we
      fabricate black phosphorus nanoparticles (BP NPs) by solution based
      electrochemical exfoliation with bipolar electrodes, which induces opposite
      potentials on the opposite ends of black phosphorus macroparticles thereby
      leading to its decomposition into nanoparticles. BP NPs have enhanced catalytic
      effect on the hydrogen evolution reaction (HER) relative to black phosphorus
      macroparticles. We utilize black phosphorus nanoparticles as electrocatalytic
      tags in a competitive immunoassay for rabbit immunoglobulin G (IgG) detection.
      The detection signal is produced via nanoimpacts of the BP NPs followed by HER
      catalysis.

PMID- 27709883
TI  - A Unique Mdm2-Binding Mode of the 3-Pyrrolin-2-one- and 2-Furanone-Based
      Antagonists of the p53-Mdm2 Interaction.
AB  - The p53 pathway is inactivated in almost all types of cancer by mutations in the
      p53 encoding gene or overexpression of the p53 negative regulators, Mdm2 and/or
      Mdmx. Restoration of the p53 function by inhibition of the p53-Mdm2/Mdmx
      interaction opens up a prospect for a nongenotoxic anticancer therapy. Here, we
      present the syntheses, activities, and crystal structures of two novel classes of
      Mdm2-p53 inhibitors that are based on the 3-pyrrolin-2-one and 2-furanone
      scaffolds. The structures of the complexes formed by these inhibitors and Mdm2
      reveal the dimeric protein molecular organization that has not been observed in
      the small-molecule/Mdm2 complexes described until now. In particular, the 6
      chloroindole group does not occupy the usual Trp-23 pocket of Mdm2 but instead is
      engaged in dimerization. This entirely unique binding mode of the compounds opens
      new possibilities for optimization of the Mdm2-p53 interaction inhibitors.

PMID- 27709885
TI  - Cyclohepta[b]indoles: A Privileged Structure Motif in Natural Products and Drug
      Design.
AB  - Seven-membered rings fused with an indole are termed cyclohepta[b]indoles.
      Compounds exhibiting this structure motif display a broad spectrum of biological
      activities, ranging from inhibition of adipocyte fatty-acid-binding protein (A
      FABP), deacetylation of histones, inhibition of leukotriene production p53,
      antituberculosis activities, and anti-HIV activities. These biological profiles
      are found in natural products containing the cyclohepta[b]indole motif, as well
      as in pharmaceuticals that contain this structure motif. Therefore, the biology
      of molecules derived from the skeleton of cyclohepta[b]indoles, as well as
      cyclopenta- and cyclohexa[b]indoles, has attracted considerable interest from the
      pharmaceutical industry as potential therapeutics in recent years. This is
      reflected by more than two dozen patents that have been issued in the past
      decade, solely based on the cyclohepta[b]indole structure motif. The efficient
      preparation of highly functionalized and unsymmetrically substituted
      cyclohepta[b]indoles has therefore become of central interest for synthetic
      organic chemists. Historically, this structure motif most often has been prepared
      by means of a Fischer indole synthesis. Although very robust and useful, this
      reaction poses certain limitations. Especially unsymmetrically functionalized
      cyclohepta[b]indoles are not suitable for a Fischer indole type synthesis, since
      product mixtures are inevitable. Therefore, novel methodologies to overcome these
      synthetic obstacles have been developed in recent years. This Account introduces
      all natural products and pharmaceutical compounds exhibiting the
      cyclohepta[b]indole motif. The structural variability within cyclohepta[b]indole
      alkaloids in combination with the broad range of organisms where these alkaloids
      have been isolated from, strongly suggests that the cyclohepta[b]indole is
      somehow a "privileged" structure motif. The organisms producing these compounds
      range from evergreen trees (actinophyllic acid) to cyanobacteria (ambiguinines).
      The synthetic methodologies to construct these molecular scaffolds (natural and
      unnatural in origin) are in turn highlighted and discussed with regard to their
      potential to access highly functionalized and unsymmetrical cyclohepta[b]indoles,
      for which they specifically have been designed. The methods are classified with
      respect to reaction type and whether or not they are enantioselective. Finally,
      the syntheses of cyclohepta[b]indole natural products are presented, thereby in
      each case, focusing on the construction of this structure motif in the course of
      the respective total synthesis. As a conclusion, we end by contrasting the
      methodological progress in the field with the actual successful application of
      the newly developed methods to the synthesis of complex structures to pinpoint
      the urgent requirement for further synthetic development for efficient synthetic
      design of this "privileged" structure motif.

PMID- 27709886
TI  - The Dynamics Behind the Affinity: Controlling Heme-Gas Affinity via Geminate
      Recombination and Heme Propionate Conformation in the NO Carrier Cytochrome c'.
AB  - Nitric oxide (NO) sensors are heme proteins which may also bind CO and O2.
      Control of heme-gas affinity and their discrimination are achieved by the
      structural properties and reactivity of the heme and its distal and proximal
      environments, leading to several energy barriers. In the bacterial NO sensor
      cytochrome c' from Alcaligenes xylosoxidans (AXCP), the single Leu16Ala distal
      mutation boosts the affinity for gas ligands by a remarkable 106-108-fold,
      transforming AXCP from one of the lowest affinity gas binding proteins to one of
      the highest. Here, we report the dynamics of diatomics after photodissociation
      from wild type and L16A-AXCP over 12 orders of magnitude in time. For the L16A
      variant, the picosecond geminate rebinding of both CO and NO appears with an
      unprecedented 100% yield, and no exit of these ligands from protein to solvent
      could be observed. Molecular dynamic simulations saliently demonstrate that
      dissociated CO stays within 4 A from Fe2+, in contrast to wild-type AXCP. The
      L16A mutation confers a heme propionate conformation and docking site which traps
      the diatomics, maximizing the probability of recombination and directly
      explaining the ultrahigh affinities for CO, NO, and O2. Overall, our results
      point to a novel mechanism for modulating heme-gas affinities in proteins.

PMID- 27709887
TI  - Polydopamine Nanoparticles Modulating Stimuli-Responsive PNIPAM Hydrogels with
      Cell/Tissue Adhesiveness.
AB  - Stimuli-responsive hydrogels can respond to stimuli by phase transformation or
      volume change and exhibit specific functions. Near-infrared (NIR)-responsive
      hydrogel is a type of stimuli-responsive hydrogel, which can be precisely
      controlled by altering the radiation intensity, exposure time of the light
      source, and irradiation sites. Here, polydopamine nanoparticles (PDA-NPs) were
      introduced into a poly(N-isopropylacrylamide) (PNIPAM) network to fabricate a PDA
      NPs/PNIPAM hydrogel with NIR responsibility, self-healing ability, and
      cell/tissue adhesiveness. After incorporation of PDA-NPs into the hydrogel, the
      PDA-NPs/PNIPAM hydrogel showed phase transitions and volume changes in response
      to NIR. Thus, the hydrogel can achieve triple response effects, including
      pulsatile drug release, NIR-driven actuation, and NIR-assisted healing. After
      coating PDA-NPs onto hydrogel surfaces, the hydrogel showed improved cell
      affinity, good tissue adhesiveness, and growth factor/protein immobilization
      ability because of reactive catechol groups on PDA-NPs. The tissue adhesion
      strength to porcine skin was as high as 90 KPa. In vivo full-skin defect
      experiments demonstrated that PDA-NPs coating on the hydrogel and an immobilized
      growth factor had a synergistic effect on accelerating wound healing. In summary,
      we combined thermosensitive PNIPAM and mussel-inspired PDA-NPs to form a NIR
      responsive hydrogel, which may have potential applications for chemical and
      physical therapies.

PMID- 27709888
TI  - Polymerization of Monomeric Ionic Liquid Confined within Uniaxial Alumina Pores
      as a New Way of Obtaining Materials with Enhanced Conductivity.
AB  - Broadband dielectric spectroscopy (BDS) and differential scanning calorimetry
      (DSC) have been employed to probe dynamics and charge transport of 1-butyl-3
      vinylimidazolium bis(trifluoromethanesulfonyl)imide ([bvim][NTf2]) confined in
      native uniaxial AAO pores as well as to study kinetics of radical polymerization
      of the examined compound as a function of the degree of confinement.
      Subsequently, the electronic conductivity of the produced polymers was
      investigated. As observed, polymerization carried out at T = 363 K proceeds
      faster under confinement with some saturation effect observed for the sample in
      pores of smaller diameter. Obtained results were discussed in the context of the
      very recent reports showing that the free volume of the confined material is
      higher with respect to the bulk one. It was also noted that conductivity of
      poly[bvim][NTf2] is significantly higher with respect to the macromolecules
      obtained upon bulk polymerization. Moreover, charge transport of the confined
      macromolecules is even higher when compared to the bulk monomeric ionic liquid at
      some thermodynamic conditions. Additionally, the molecular weight, Mw, of the
      confined-synthesized polymers is significantly higher with respect to the bulk
      synthesized material. Interestingly, both parameters, (i) the enhancement of
      sigmadc and (ii) the increase in Mw, can be tuned and controlled by the
      application of the appropriate confinement. Consequently, those results are quite
      promising in the context of development of the fabrication of polymerized ionic
      liquids (PILs) nanomaterials with unique properties and morphologies, which can
      be further easily applied in the field of nanotechnology.

PMID- 27709889
TI  - Silicon-Reduced Graphene Oxide Self-Standing Composites Suitable as Binder-Free
      Anodes for Lithium-Ion Batteries.
AB  - Silicon-reduced graphene oxide (Si-rGO) composites processed as self-standing
      aerogels (0.2 g cm-3) and films (1.5 g cm-3) have been prepared by the thermal
      reduction of composites formed between silicon nanoparticles and a suspension of
      graphene oxide (GO) in ethanol. The characterization of the samples by different
      techniques (X-ray diffraction, Raman, thermogravimetric analysis, and scanning
      electron microscopy) show that in both cases the composites are formed by rGO
      sheets homogeneously decorated with 50 nm silicon nanoparticles with silicon
      contents of ~40% wt. The performances of these self-standing materials were
      tested as binder-free anodes in lithium-ion batteries (LIBs) in a half cell
      configuration under two different galvanostatic charge-discharge cutoff voltages
      (75 and 50 mV). The results show that the formation of a solid electrolyte
      interphase (SEI) is favored in composites processed as aerogels due to its large
      exposed surface, which prevents the activation of silicon when they are cycled
      within the 2 to 0.075 V voltage windows. It is also found that the composites
      processed in the form of self-standing films exhibit good stability over the
      first 100 cycles, high reversible specific capacity per mass of electrode (~750
      mAh g-1), areal capacities that reach 0.7 mAh cm-2, and high Coulombic
      efficiencies (80% for the first charge-discharge cycle and over 99% in the
      subsequent cycles).

PMID- 27709890
TI  - A Biodegradable Polycationic Paint that Kills Bacteria in Vitro and in Vivo.
AB  - Bacterial colonization and subsequent formation of biofilms onto surfaces of
      medical devices and implants is a major source of nosocomial infections. Most
      antibacterial coatings to combat infections are either metal-based or
      nondegradable-polymer-based and hence limited by their nondegradability and
      unpredictable toxicity. Moreover, to combat infections effectively, the coatings
      are required to display simultaneous antibacterial and antibiofilm activity.
      Herein we report biocompatible and biodegradable coatings based on organo-soluble
      quaternary chitin polymers which were immobilized noncovalently onto surfaces as
      bactericidal paint. The polycationic paint was found to be active against both
      drug-sensitive and -resistant bacteria such as methicillin-resistant
      Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE),
      and beta-lactam-resistant Klebsiella pneumoniae. The cationic polymers were shown
      to interact with the negatively charged bacterial cell membrane and disrupt the
      membrane integrity, thereby causing leakage of intracellular constituents and
      cell death upon contact. Importantly, surfaces coated with the polymers inhibited
      formation of biofilms against both Gram-positive S. aureus and Gram-negative E.
      coli, two of the most clinically important bacteria that form biofilms. Surfaces
      coated with the polymers displayed negligible toxicity against human erythrocytes
      and embryo kidney cells. Notably, the polymers were shown to be susceptible
      toward lysozyme. Furthermore, subcutaneous implantation of polymer discs in rats
      led to 15-20% degradation in 4 weeks thereby displaying their biodegradability.
      In a murine model of subcutaneous infection, polymer-coated medical-grade
      catheter reduced MRSA burden by 3.7 log compared to that of noncoated catheter.
      Furthermore, no biofilm development was observed on the coated catheters under in
      vivo conditions. The polycationic materials thus developed herein represent a
      novel class of safe and effective coating agents for the prevention of device
      associated infections.

PMID- 27709891
TI  - Correction to Facile, Fast-Responsive, and Photostable Imaging of Telomerase
      Activity in Living Cells with a Fluorescence Turn-On Manner.

PMID- 27709893
TI  - Development and Calibration of an Organic-Diffusive Gradients in Thin Films
      Aquatic Passive Sampler for a Diverse Suite of Polar Organic Contaminants.
AB  - A unique configuration of the diffusive gradients in thin films sampler for polar
      organics (o-DGT) without a poly(ether sulfone) membrane was developed,
      calibrated, and field-evaluated. Diffusion coefficients (D) through agarose
      diffusive gels ranged from (1.02 to 4.74) * 10-6 cm2/s for 34 pharmaceuticals and
      pesticides at 5, 13, and 23  degrees C. Analyte-specific diffusion-temperature
      plots produced linear (r2 > 0.85) empirical relationships whereby D could be
      estimated at any environmentally relevant temperature (i.e., matched to in situ
      water conditions). Linear uptake for all analytes was observed in a static
      renewal calibration experiment over 25 days except for three macrolide
      antibiotics, which reached saturation at 300 ng (~15 d). Experimental sampling
      rates ranged from 8.8 to 16.1 mL/d and were successfully estimated with measured
      and modeled D within 19% and 30% average relative error, respectively. Under slow
      flowing (2.4 cm/s) and static conditions, the in situ diffusive boundary layer
      (DBL) thickness ranged from 0.023 to 0.075 cm, resulting in a maximum
      contribution to mass transfer of <45%. Estimated water concentrations by o-DGT at
      a wastewater treatment plant agreed well with grab samples and appeared to be
      less influenced by the boundary layer compared to that of polar organic chemical
      integrative samplers (POCIS) deployed simultaneously. The o-DGT sampler is a
      promising monitoring tool that is largely insensitive to the DBL under typical
      flow conditions, facilitating the application of measured/modeled diffusion-based
      sampling rates. This significantly reduces the need for sampler calibration,
      making o-DGT more widely applicable, reliable, and cost-effective compared to
      current polar passive samplers.

PMID- 27709892
TI  - Current Challenges toward In Vitro Cellular Validation of Inorganic
      Nanoparticles.
AB  - An impressive development has been achieved toward the production of well-defined
      "smart" inorganic nanoparticles, in which the physicochemical properties can be
      controlled and predicted to a high degree of accuracy. Nanoparticle design is
      indeed highly advanced, multimodal and multitargeting being the norm, yet we do
      not fully understand the obstacles that nanoparticles face when used in vivo.
      Increased cooperation between chemists and biochemists, immunologists and
      physicists, has allowed us to think outside the box, and we are slowly starting
      to understand the interactions that nanoparticles undergo under more realistic
      situations. Importantly, such an understanding involves awareness about the
      limitations when assessing the influence of such inorganic nanoparticles on
      biological entities and vice versa, as well as the development of new validation
      strategies.

PMID- 27709894
TI  - In Vitro Toxicity Evaluation of Lignin-(Un)coated Cellulose Based Nanomaterials
      on Human A549 and THP-1 Cells.
AB  - A significant amount of research toward commercial development of cellulose based
      nanomaterials (CNM) is now in progress with some potential applications. Using
      human A549 and THP-1 cells, we evaluated the biological responses of various
      CNMs, made out of similar material but with functional and morphological
      variations. While A549 cells displayed minimal or no cytotoxic responses
      following exposure to CNMs, THP-1 cells were more susceptible to cytotoxicity,
      cellular damage and inflammatory responses. Further analysis of these biological
      responses evaluated using hierarchical clustering approaches was effective in
      discriminating (dis)-similarities of various CNMs studied and identified
      potential inflammatory factors contributing to cytotoxicity. No correlation
      between cytotoxicity and surface properties of CNMs was found. This study clearly
      highlights that, in addition to the source and characteristics of CNMs, cell type
      specific differences in the recognition/uptake of CNMs along with their inherent
      capability to respond to external stimuli are crucial for assessing the toxicity
      of CNMs.

PMID- 27709895
TI  - Multiplex Biosensing Based on Highly Sensitive Magnetic Nanolabel Quantification:
      Rapid Detection of Botulinum Neurotoxins A, B, and E in Liquids.
AB  - We present a multiplex quantitative lateral flow (LF) assay for simultaneous on
      site detection of botulinum neurotoxin (BoNT) types A, B, and E in complex
      matrixes, which is innovative by virtually no sacrifice in performance while
      transition from the single-plex assays and by characteristics on the level of
      laboratory quantitative methods. The novel approach to easy multiplexing is
      realized via joining an on-demand set of single-plex LF strips, which employ
      magnetic nanolabels, into a miniature cylinder cartridge that mimics LF strip
      during all assay stages. The cartridge is read out by an original portable
      multichannel reader based on the magnetic particle quantification technique. The
      developed reader offers the unmatched 60 zmol detection limit and 7-order linear
      dynamic range for volumetric registration of magnetic labels inside a cartridge
      of several millimeters in diameter regardless of its optical transparency. Each
      of the test strips, developed here as building blocks for the multiplex assay,
      can be used "as is" for autonomous quantitative single-plex detection with the
      same measuring setup, exhibiting the limits of detection (LOD) of 0.22, 0.11, and
      0.32 ng/mL for BoNT-A, -B, and -E, respectively. The proposed multiplex assay has
      demonstrated the remarkably similar LOD values of 0.20, 0.12, 0.35 ng/mL under
      the same conditions. The multiplex assay performance was successfully validated
      by BoNT detection in milk and apple and orange juices. The developed methods can
      be extended to other proteins and used for rapid multianalyte tests for point-of
      care in vitro diagnostics, food analysis, biosafety and environmental monitoring,
      forensics, and security, etc.

PMID- 27709896
TI  - Tissue Characterization with Quantitative High-Resolution Magic Angle Spinning
      Chemical Exchange Saturation Transfer Z-Spectroscopy.
AB  - Chemical exchange saturation transfer (CEST) provides sensitive magnetic
      resonance (MR) contrast for probing dilute compounds via exchangeable protons,
      serving as an emerging molecular imaging methodology. CEST Z-spectrum is often
      acquired by sweeping radiofrequency saturation around bulk water resonance,
      offset by offset, to detect CEST effects at characteristic chemical shift
      offsets, which requires prolonged acquisition time. Herein, combining high
      resolution magic angle spinning (HRMAS) with concurrent application of gradient
      and rf saturation to achieve fast Z-spectral acquisition, we demonstrated the
      feasibility of fast quantitative HRMAS CEST Z-spectroscopy. The concept was
      validated with phantoms, which showed excellent agreement with results obtained
      from conventional HRMAS MR spectroscopy (MRS). We further utilized the HRMAS Z
      spectroscopy for fast ex vivo quantification of ischemic injury with rodent brain
      tissues after ischemic stroke. This method allows rapid and quantitative CEST
      characterization of biological tissues and shows potential for a host of
      biomedical applications.

PMID- 27709898
TI  - Aerosol Chemistry Resolved by Mass Spectrometry: Linking Field Measurements of
      Cloud Condensation Nuclei Activity to Organic Aerosol Composition.
AB  - Aerosol hygroscopic properties were linked to its chemical composition by using
      complementary online mass spectrometric techniques in a comprehensive chemical
      characterization study at a rural mountaintop station in central Germany in
      August 2012. In particular, atmospheric pressure chemical ionization mass
      spectrometry ((-)APCI-MS) provided measurements of organic acids, organosulfates,
      and nitrooxy-organosulfates in the particle phase at 1 min time resolution.
      Offline analysis of filter samples enabled us to determine the molecular
      composition of signals appearing in the online (-)APCI-MS spectra. Aerosol mass
      spectrometry (AMS) provided quantitative measurements of total submicrometer
      organics, nitrate, sulfate, and ammonium. Inorganic sulfate measurements were
      achieved by semionline ion chromatography and were compared to the AMS total
      sulfate mass. We found that up to 40% of the total sulfate mass fraction can be
      covalently bonded to organic molecules. This finding is supported by both on- and
      offline soft ionization techniques, which confirmed the presence of several
      organosulfates and nitrooxy-organosulfates in the particle phase. The chemical
      composition analysis was compared to hygroscopicity measurements derived from a
      cloud condensation nuclei counter. We observed that the hygroscopicity parameter
      (kappa) that is derived from organic mass fractions determined by AMS
      measurements may overestimate the observed kappa up to 0.2 if a high fraction of
      sulfate is bonded to organic molecules and little photochemical aging is
      exhibited.

PMID- 27709897
TI  - Comparing Gene Silencing and Physiochemical Properties in siRNA Bound Cationic
      Star-Polymer Complexes.
AB  - The translation of siRNA into clinical therapies has been significantly delayed
      by issues surrounding the delivery of naked siRNA to target cells. Here we
      investigate siRNA delivery by cationic acrylic polymers developed by Reversible
      Addition-Fragmentation chain Transfer (RAFT) mediated free radical
      polymerization. We investigated cell uptake and gene silencing of a series of
      siRNA-star polymer complexes both in the presence and absence of a protein
      "corona". Using a multidisciplinary approach including quantitative nanoscale
      mechanical-atomic force microscopy, dynamic light scattering and nanoparticle
      tracking analysis we have characterized the nanoscale morphology, stiffness, and
      surface charge of the complexes with and without the protein corona. This is one
      of the first examples of a comprehensive physiochemical analysis of siRNA-polymer
      complexes being performed alongside in vitro biological assays, allowing us to
      describe a set of desirable physical features of cationic polymer complexes that
      promote gene silencing. Multifaceted studies such as this will improve our
      understanding of structure-function relationships in nanotherapeutics,
      facilitating the rational design of polymer-mediated siRNA delivery systems for
      novel treatment strategies.

PMID- 27709899
TI  - PGMA-Based Cationic Nanoparticles with Polyhydric Iodine Units for Advanced Gene
      Vectors.
AB  - It is crucial for successful gene delivery to develop safe, effective, and
      multifunctional polycations. Iodine-based small molecules are widely used as
      contrast agents for CT imaging. Herein, a series of star-like poly(glycidyl
      methacrylate) (PGMA)-based cationic vectors (II-PGEA/II) with abundant flanking
      polyhydric iodine units are prepared for multifunctional gene delivery systems.
      The proposed II-PGEA/II star vector is composed of one iohexol intermediate (II)
      core and five ethanolamine (EA) and II-difunctionalized PGMA arms. The
      amphipathic II-PGEA/II vectors readily self-assemble into well-defined cationic
      nanoparticles, where massive hydroxyl groups can establish a hydration shell to
      stabilize the nanoparticles. The II introduction improves cell viabilities of
      polycations. Moreover, by controlling the suitable amount of introduced II units,
      the resultant II-PGEA/II nanoparticles can produce fairly good transfection
      performances in different cell lines. Particularly, the II-PGEA/II nanoparticles
      induce much better in vitro CT imaging abilities in tumor cells than iohexol (one
      commonly used commercial CT contrast agent). The present design of amphipathic
      PGMA-based nanoparticles with CT contrast agents would provide useful information
      for the development of new multifunctional gene delivery systems.

PMID- 27709900
TI  - Aerosol Chemistry Resolved by Mass Spectrometry: Insights into Particle Growth
      after Ambient New Particle Formation.
AB  - Atmospheric oxidation of volatile organic compounds (VOCs) yields a large number
      of different organic molecules which comprise a wide range of volatility.
      Depending on their volatility, they can be involved in new particle formation and
      particle growth, thus affecting the number concentration of cloud condensation
      nuclei in the atmosphere. Here, we identified oxidation products of VOCs in the
      particle phase during a field study at a rural mountaintop station in central
      Germany. We used atmospheric pressure chemical ionization mass spectrometry ((
      )APCI-MS) and aerosol mass spectrometry for time-resolved measurements of organic
      species and of the total organic aerosol (OA) mass in the size range of 0.02-2.5
      and 0.05-0.6 MUm, respectively. The elemental composition of organic molecules
      was determined by offline analysis of colocated PM 2.5 filter samples using
      liquid chromatography coupled to electrospray ionization ultrahigh-resolution
      mass spectrometry. We found extremely low volatile organic compounds, likely from
      sesquiterpene oxidation, being the predominant signals in the (-)APCI-MS mass
      spectrum during new particle formation. Low volatile organic compounds started to
      dominate the spectrum when the newly formed particles were growing to larger
      diameters. Furthermore, the APCI-MS mass spectra pattern indicated that the
      average molecular weight of the OA fraction ranged between 270 and 340 amu, being
      inversely related to OA mass. Our observations can help further the understanding
      of which biogenic precursors and which chemical processes drive particle growth
      after atmospheric new-particle formation.

PMID- 27709901
TI  - Effects of C60 on the Photochemical Formation of Reactive Oxygen Species from
      Natural Organic Matter.
AB  - Buckminsterfullerenes (C60) are widely used nanomaterials that are present in
      surface water. The combination of C60 and humic acid (HA) generates reactive
      oxygen species (ROS) under solar irradiation, but this process is not well
      understood. Thus, the present study focused on the photochemical formation of
      singlet oxygen (1O2), hydroxyl radical (HO*)-like species, superoxide radicals
      (O2*-), hydrogen peroxide (H2O2), and triplet excited states (3C60*/3HA*) in
      solutions containing both C60 and HA. The quantum yield coefficients of excited
      triplet states (fTMP) and apparent quantum yields of ROS were measured and
      compared to the calculated values, which were based on the conservative mixing
      model. Although C60 proved to have only a slight impact on the 1O2 formation from
      HA, C60 played a key role in the inhibition of O2*-. The photochemical formation
      of H2O2 followed the conservative mixing model due to the reaction of C60*- with
      HO2*/O2*-, and the biomolecular reaction rate constant has been measured as (7.4
      +/- 0.6) * 106 M-1 s-1. The apparent fTMP was significantly lower than the
      calculated value, indicating that the steric effect of HA was significant in the
      reaction of 3C60* with the TMP probe. In contrast, C60 did not have an effect on
      the photochemical formation of HO* from HA, suggesting that HO* is elevated from
      the hydrophilic surface of HA. The aforementioned results may be useful for
      predicting the photochemical influence of C60 on aqueous environments.

PMID- 27709902
TI  - Enrichment of Saccharides and Divalent Cations in Sea Spray Aerosol During Two
      Phytoplankton Blooms.
AB  - Sea spray aerosol (SSA) is a globally important source of particulate matter. A
      mesocosm study was performed to determine the relative enrichment of saccharides
      and inorganic ions in nascent fine (PM2.5) and coarse (PM10-2.5) SSA and the sea
      surface microlayer (SSML) relative to bulk seawater. Saccharides comprise a
      significant fraction of organic matter in fine and coarse SSA (11 and 27%,
      respectively). Relative to sodium, individual saccharides were enriched 14-1314
      fold in fine SSA, 3-138-fold in coarse SSA, but only up to 1.0-16.2-fold in SSML.
      Enrichments in SSML were attributed to rising bubbles that scavenge surface
      active species from seawater, while further enrichment in fine SSA likely derives
      from bubble films. Mean enrichment factors for major ions demonstrated
      significant enrichment in fine SSA for potassium (1.3), magnesium (1.4), and
      calcium (1.7), likely because of their interactions with organic matter.
      Consequently, fine SSA develops a salt profile significantly different from that
      of seawater. Maximal enrichments of saccharides and ions coincided with the
      second of two phytoplankton blooms, signifying the influence of ocean biology on
      selective mass transfer across the ocean-air interface.

PMID- 27709903
TI  - In Situ Molecular Imaging of the Biofilm and Its Matrix.
AB  - Molecular mapping of live biofilms at submicrometer resolution presents a grand
      challenge. Here, we present the first chemical mapping results of biofilm
      extracellular polymeric substance (EPS) in biofilms using correlative imaging
      between super resolution fluorescence microscopy and liquid time-of-flight
      secondary ion mass spectrometry (TOF-SIMS). Shewanella oneidensis is used as a
      model organism. Heavy metal chromate (Cr2O72-) anions consisting of chromium
      Cr(VI) was used as a model environmental stressor to treat the biofilms. Of
      particular interest, biologically relevant water clusters have been first
      observed in the biofilms. Characteristic fragments of biofilm matrix components
      such as proteins, polysaccharides, and lipids can be spatially imaged.
      Furthermore, characteristic fatty acids (e.g., palmitic acid), quinolone signal,
      and riboflavin fragments were found to respond after the biofilm is treated with
      Cr(VI), leading to biofilm dispersal. Significant changes in water clusters and
      quorum sensing signals indicative of intercellular communication in the aqueous
      environment were observed, suggesting that they might result in fatty acid
      synthesis and inhibition of riboflavin production. The Cr(VI) reduction seems to
      follow the Mtr pathway leading to Cr(III) formation. Our approach potentially
      opens a new avenue for mechanistic insight of microbial community processes and
      communications using in situ imaging mass spectrometry and super resolution
      optical microscopy.

PMID- 27709904
TI  - Endotoxins: The Critical Risk Factor in Reclaimed Water via Inhalation Exposure.
AB  - The use of reclaimed water for nonpotable uses requires consideration of
      potential adverse health effects. Considering that inhalation can be a
      significant route of transmission of microorganisms and inflammatory agents, this
      study used a mouse model to test the possible adverse effects of reclaimed water
      use during car washing where aerosols are generated. Intensive innate immune
      responses were found in the lungs after acute exposure, and the lavage
      polymorphonuclear cell proportion was the most sensitive end point. Four types of
      evidence are presented to demonstrate that the main risk factor that initiates
      innate inflammation is the free endotoxin. (1) Small molecules (<10 kDa) cannot
      induce inflammation. (2) The endotoxin levels of 11 water samples from five
      different plants showed positive correlations with inflammatory responses. (3)
      Actual water samples showed similar activities with free endotoxins other than
      bacterially bound endotoxins. (4) Specific removal of endotoxins with polymyxin B
      affinity chromatography further confirmed the role of free endotoxins. It is
      noteworthy that 62.9% of the investigated tertiary-treated water had endotoxin
      levels higher than the allowable acute threshold (120 endotoxin units/mL) under
      the hypothesized car wash condition, which strongly suggests the need to
      carefully consider the water treatment steps required to produce safe water for
      various reclaimed water end uses.

PMID- 27709906
TI  - Fully Automated Portable Comprehensive 2-Dimensional Gas Chromatography Device.
AB  - We developed a fully automated portable 2-dimensional (2-D) gas chromatography
      (GC x GC) device, which had a dimension of 60 cm * 50 cm * 10 cm and weight less
      than 5 kg. The device incorporated a micropreconcentrator/injector, commercial
      columns, micro-Deans switches, microthermal injectors, microphotoionization
      detectors, data acquisition cards, and power supplies, as well as computer
      control and user interface. It employed multiple channels (4 channels) in the
      second dimension (2D) to increase the 2D separation time (up to 32 s) and hence
      2D peak capacity. In addition, a nondestructive flow-through vapor detector was
      installed at the end of the 1D column to monitor the eluent from 1D and assist in
      reconstructing 1D elution peaks. With the information obtained jointly from the
      1D and 2D detectors, 1D elution peaks could be reconstructed with significantly
      improved 1D resolution. In this Article, we first discuss the details of the
      system operating principle and the algorithm to reconstruct 1D elution peaks,
      followed by the description and characterization of each component. Finally, 2-D
      separation of 50 analytes, including alkane (C6-C12), alkene, alcohol, aldehyde,
      ketone, cycloalkane, and aromatic hydrocarbon, in 14 min is demonstrated, showing
      the peak capacity of 430-530 and the peak capacity production of 40-80/min.

PMID- 27709905
TI  - Complete Molecular Weight Profiling of Low-Molecular Weight Heparins Using Size
      Exclusion Chromatography-Ion Suppressor-High-Resolution Mass Spectrometry.
AB  - Low-molecular weight heparins (LMWH) prepared by partial depolymerization of
      unfractionated heparin are used globally to treat coagulation disorders on an
      outpatient basis. Patent protection for several LMWH has expired and abbreviated
      new drug applications have been approved by the Food and Drug Administration. As
      a result, reverse engineering of LMWH for biosimilar LMWH has become an active
      global endeavor. Traditionally, the molecular weight distributions of LMWH
      preparations have been determined using size exclusion chromatography (SEC) with
      optical detection. Recent advances in liquid chromatography-mass spectrometry
      methods have enabled exact mass measurements of heparin saccharides roughly up to
      degree-of-polymerization 20, leaving the high molecular weight half of the LMWH
      preparation unassigned. We demonstrate a new LC-MS system capable of determining
      the exact masses of complete LMWH preparations, up to dp30. This system employed
      an ion suppressor cell to desalt the chromatographic effluent online prior to the
      electrospray mass spectrometry source. We expect this new capability will impact
      the ability to define LMWH mixtures favorably.

PMID- 27709907
TI  - Synthesis and Functionalization of Porphyrins through Organometallic
      Methodologies.
AB  - This review focuses on the postfunctionalization of porphyrins and related
      compounds through catalytic and stoichiometric organometallic methodologies. The
      employment of organometallic reactions has become common in porphyrin synthesis.
      Palladium-catalyzed cross-coupling reactions are now standard techniques for
      constructing carbon-carbon bonds in porphyrin synthesis. In addition, iridium- or
      palladium-catalyzed direct C-H functionalization of porphyrins is emerging as an
      efficient way to install various substituents onto porphyrins. Furthermore, the
      copper-mediated Huisgen cycloaddition reaction has become a frequent strategy to
      incorporate porphyrin units into functional molecules. The use of these
      organometallic techniques, along with the traditional porphyrin synthesis, now
      allows chemists to construct a wide range of highly elaborated and complex
      porphyrin architectures.

PMID- 27709908
TI  - Genetic, Structural, and Phenotypic Properties of MS2 Coliphage with Resistance
      to ClO2 Disinfection.
AB  - Common water disinfectants like chlorine have been reported to select for
      resistant viruses, yet little attention has been devoted to characterizing
      disinfection resistance. Here, we investigated the resistance of MS2 coliphage to
      inactivation by chlorine dioxide (ClO2). ClO2 inactivates MS2 by degrading its
      structural proteins, thereby disrupting the ability of MS2 to attach to and
      infect its host. ClO2-resistant virus populations emerged not only after repeated
      cycles of ClO2 disinfection followed by regrowth but also after dilution-regrowth
      cycles in the absence of ClO2. The resistant populations exhibited several fixed
      mutations which caused the substitution of ClO2-labile by ClO2-stable amino
      acids. On a phenotypic level, these mutations resulted in a more stable host
      binding during inactivation compared to the wild-type, thus resulting in a
      greater ability to maintain infectivity. This conclusion was supported by cryo
      electron microscopy reconstruction of the virus particle, which demonstrated that
      most structural modification occurred in the putative A protein, an important
      binding factor. Resistance was specific to the inactivation mechanism of ClO2 and
      did not result in significant cross-resistance to genome-damaging disinfectants.
      Overall, our data indicate that resistant viruses may emerge even in the absence
      of ClO2 pressure but that they can be inactivated by other common disinfectants.

PMID- 27709909
TI  - Engineering Biological C-H Functionalization Leads to Allele-Specific Regulation
      of Histone Demethylases.
AB  - Oxidative C-H hydroxylation of methyl groups, followed by their removal from DNA,
      RNA or histones, is an epigenetic process critical to transcriptional
      reprogramming and cell fate determination. This reaction is catalyzed by Fe(II)
      dependent dioxygenases using the essential metabolite 2-ketoglutarate (2KG) as a
      cofactor. Given that the human genome encodes for more than 60 2KG-dependent
      dioxygenases, assigning their individual functions remains a significant
      challenge. Here we describe a protein-ligand interface engineering approach to
      break the biochemical degeneracy of these enzymes. Using histone lysine
      demethylase 4 (KDM4) as a proof-of-concept, we show that the enzyme active site
      can be expanded to employ bulky 2KG analogues that do not sensitize wild type
      demethylases. We establish the orthogonality, substrate specificity and catalytic
      competency of the engineered demethylation apparatus in biochemical assays. We
      further demonstrate demethylation of cognate substrates in physiologically
      relevant settings. Our results provide a para-digm for rapid and conditional
      manipulation of histone deme-thylases to uncloak their isoform-specific
      functions.

PMID- 27709910
TI  - Scenarios for Low Carbon and Low Water Electric Power Plant Operations:
      Implications for Upstream Water Use.
AB  - Electric sector water use, in particular for thermoelectric operations, is a
      critical component of the water-energy nexus. On a life cycle basis per unit of
      electricity generated, operational (e.g., cooling system) water use is
      substantially higher than water demands for the fuel cycle (e.g., natural gas and
      coal) and power plant manufacturing (e.g., equipment and construction). However,
      could shifting toward low carbon and low water electric power operations create
      trade-offs across the electricity life cycle? We compare business-as-usual with
      scenarios of carbon reductions and water constraints using the MARKet ALlocation
      (MARKAL) energy system model. Our scenarios show that, for water withdrawals, the
      trade-offs are minimal: operational water use accounts for over 95% of life cycle
      withdrawals. For water consumption, however, this analysis identifies potential
      trade-offs under some scenarios. Nationally, water use for the fuel cycle and
      power plant manufacturing can reach up to 26% of the total life cycle
      consumption. In the western United States, nonoperational consumption can even
      exceed operational demands. In particular, water use for biomass feedstock
      irrigation and manufacturing/construction of solar power facilities could
      increase with high deployment. As the United States moves toward lower carbon
      electric power operations, consideration of shifting water demands can help avoid
      unintended consequences.

PMID- 27709911
TI  - Catalytic, Regioselective Hydrocarbofunctionalization of Unactivated Alkenes with
      Diverse C-H Nucleophiles.
AB  - Reactions that forge carbon-carbon (C-C) bonds are the bedrock of organic
      synthesis, widely used across the chemical sciences. We report a transformation
      that enables C-C bonds to be constructed from two classes of commonly available
      starting materials, alkenes and carbon-hydrogen (C-H) bonds. The reaction employs
      a palladium(II) catalyst and utilizes a removable directing group to both control
      the regioselectivity of carbopalladation and enable subsequent
      protodepalladation. A wide range of alkenes and C-H nucleophiles, including 1,3
      dicarbonyls, aryl carbonyls, and electron-rich aromatics, are viable reaction
      partners, allowing Michael-type reactivity to be expanded beyond alpha,beta
      unsaturated carbonyl compounds to unactivated alkenes. Applications of this
      transformation in drug diversification and natural product total synthesis are
      described. Stoichiometric studies support each of the proposed steps in the
      catalytic cycle.

PMID- 27709912
TI  - Cycloaddition Reactions of the Phosphinidene-Bridged Complex [Mo2Cp(MU
      kappa1:kappa1,eta5-PC5H4)(CO)2(eta6-HMes*)] with Diazoalkanes and Other
      Heterocumulenes.
AB  - The title phosphinidene complex reacted at room temperature with CS2 and SCNPh to
      give the phosphanyl derivatives [Mo2Cp{MU-kappa2P,S:kappa1S',eta5
      P(CS2)C5H4}(CO)2(eta6-HMes*)] and [Mo2Cp{MU-kappa2P,S:kappa1P,eta5
      P(C(NPh)S)C5H4}(CO)2(eta6-HMes*)], respectively (Mes* = 2,4,6-C6H2tBu3), which
      result from a [2 + 2] cycloaddition of a C?S bond in the organic reagent to the
      Mo?P bond of the phosphinidene complex, with further insertion of S into the
      remaining Mo-P bond, in the CS2 reaction. The title complex also reacted with
      diazoalkanes N2CRR' at room temperature to give the corresponding phosphaalkene
      derivatives [Mo2Cp{MU-eta2:kappa1P,eta5-P(CRR')C5H4}(CO)2(eta6-HMes*)] (CRR' =
      CH2, CPh2, CH(SiMe3)). These products follow from a formal [2 + 1] cycloaddition
      of the carbene CRR' fragment to the Mo?P bond of the parent compound but were
      shown to proceed through a [3 + 2] cycloaddition of the diazoalkane molecule,
      followed by N2 elimination. The diazomethane reaction allowed the identification
      at low temperature of a stabilized form of the intermediate product, the
      phosphanyl complex [Mo2Cp{MU-kappa2P,N:kappa1P,eta5-P(CHN2H)C5H4}(CO)2(eta6
      HMes*)], which follows from a reversible 1,3-shift of a methylenic H atom from C
      to N. It was concluded that all of the above cycloaddition reactions are
      initiated by heteroatom coordination of the unsaturated organic molecule to the
      MoCp(CO)2 fragment in the parent phosphinidene complex, this triggering the P-C
      bond formation step which leads to the products eventually isolated. The
      structures of the new complexes were determined by spectroscopic,
      diffractometric, and (in some cases) density functional theory methods.

PMID- 27709913
TI  - New Initiation Modes for Directed Carbonylative C-C Bond Activation: Rhodium
      Catalyzed (3 + 1 + 2) Cycloadditions of Aminomethylcyclopropanes.
AB  - Under carbonylative conditions, neutral Rh(I)-systems modified with weak donor
      ligands (AsPh3 or 1,4-oxathiane) undergo N-Cbz, N-benzoyl, or N-Ts directed
      insertion into the proximal C-C bond of aminomethylcyclopropanes to generate
      rhodacyclopentanone intermediates. These are trapped by N-tethered alkenes to
      provide complex perhydroisoindoles.

PMID- 27709915
TI  - Exploiting Pressure To Induce a "Guest-Blocked" Spin Transition in a Framework
      Material.
AB  - A new functionalized 1,2,4-triazole ligand, 4-[(E)-2-(5-methyl-2-thienyl)vinyl]
      1,2,4-triazole (thiome), was prepared to assess the broad applicability of
      strategically producing multistep spin transitions in two-dimensional Hofmann
      type materials of the type [FeIIPd(CN)4(R-1,2,4-trz)2].nH2O (R-1,2,4-trz = a 4
      functionalized 1,2,4-triazole ligand). A variety of structural and magnetic
      investigations on the resultant framework material [FeIIPd(CN)4(thiome)2].2H2O
      (A.2H2O) reveal that a high-spin (HS) to low-spin (LS) transition is inhibited in
      A.2H2O due to a combination of guest and ligand steric bulk effects. The water
      molecules can be reversibly removed with retention of the porous host framework
      and result in the emergence of an abrupt and hysteretic one-step spin transition
      due to the removal of guest internal pressure. A spin transition can,
      furthermore, be induced in A.2H2O (0-0.68 GPa) under hydrostatic pressure, as
      evidenced by variable-pressure structure and magnetic studies, resulting in a two
      step spin transition at ambient temperatures at 0.68 GPa. The presence of a two
      step spin crossover (SCO) in A.2H2O under hydrostatic pressure compared to a one
      step SCO in A at ambient pressure is discussed in terms of the relative ability
      of each phase to accommodate mixed HS/LS states according to differing lattice
      flexibilities.

PMID- 27709914
TI  - Mineral Formation in the Larval Zebrafish Tail Bone Occurs via an Acidic
      Disordered Calcium Phosphate Phase.
AB  - Both in vivo and ex vivo observations support the hypothesis that bone mineral
      formation proceeds via disordered precursor phases. The characteristics of the
      precursor phases are not well defined, but octacalcium phosphate-like, amorphous
      calcium phosphate-like, and HPO42--enriched phases were detected. Here we use in
      vivo Raman spectroscopy and high-resolution wide-angle X-ray diffraction (WAXD)
      to characterize and map at 2 MUm resolution the mineral phases in the rapidly
      forming tail fin bones of living zebrafish larvae and zebrafish larvae
      immediately after sacrifice, respectively. Raman spectroscopy shows the presence
      of an acidic disordered calcium phosphate phase with additional characteristic
      features of HPO42- at the bone-cell interface. The complexity in the position and
      shape of the nu1 PO4 peak viewed by in vivo Raman spectroscopy emphasizes the
      heterogeneity of the mineral during bone formation. WAXD detects an additional
      isolated peak, appearing alone or together with the characteristic diffraction
      pattern of carbonated hydroxyapatite. This unidentified phase is located at the
      interface between the mature bone and the surrounding tissue, similar to the
      location at which the disordered phase was observed by Raman spectroscopy. The
      variable peak positions and profiles support the notion that this is an unstable
      disordered precursor phase, which conceivably crystallized during the X-ray
      diffraction measurement. Interestingly, this precursor phase is co-aligned with
      the c-axes of the mature bone crystals and thus is in intimate relation with the
      surrounding collagen matrix. We conclude that a major disordered precursor
      mineral phase containing HPO42- is part of the deposition pathway of the rapidly
      forming tail fin bones of the zebrafish.

PMID- 27709916
TI  - Supramolecular Double-Helix Formation by Diastereoisomeric Conformations of
      Configurationally Enantiomeric Macrocycles.
AB  - Solid-state superstructures, resulting from assemblies programmed by
      homochirality, are attracting considerable attention. In addition, artificial
      double-helical architectures are being investigated, especially in relation to
      the ways in which homochiral small molecules can be induced to yield helical
      forms as a result of chiral induction. Herein, we report the highly specific self
      assembly upon crystallization of a double-helical superstructure from an
      enantiopure macrocyclic dimer which adopts two diastereoisomeric conformations in
      a molar ratio of 1.5:1 in dimethyl sulfoxide. These two conformational
      diastereoisomers self-organize-and self-sort-in the crystalline phase in
      equimolar proportions to form two single-handed helices which are complementary
      to each other, giving rise to the assembly of a double helix that is stabilized
      by intermolecular [C-H...O] and pi-pi stacking interactions. The observed self
      sorting phenomenon occurs on going from a mixed-solvent system containing two
      equilibrating conformational diastereoisomers, presumably present in unequal
      molar proportions, into the solid state. The diastereoisomeric conformations are
      captured upon crystallization in a 1:1 molar ratio in the double-helical
      superstructure, whose handedness is dictated by the choice of the enantiomeric
      macrocyclic dimer. The interconversion of the two conformational diastereoisomers
      derived from each configurationally enantiomeric macrocycle was investigated in
      CD3SOCD3 solution by variable-temperature 1H NMR spectroscopy (VT NMR) and
      circular dichroism (VT CD). The merging of the resonances for the protons
      corresponding to the two diastereoisomers at a range of coalescence temperatures
      in the VT NMR spectra and occurrence of the isosbestic points in the VT CD
      spectra indicate that the two diastereoisomers are interconverting slowly in
      solution on the 1H NMR time scale but rapidly on the laboratory time scale. To
      the best of our knowledge, the self-assembly of such solid-state superstructures
      from two conformational diastereoisomers of a homochiral macrocycle is a rare, if
      not unique, occurrence.

PMID- 27709917
TI  - Alkyne Semihydrogenation with a Well-Defined Nonclassical Co-H2 Catalyst: A H2
      Spin on Isomerization and E-Selectivity.
AB  - The reactivity of a CoI-H2 complex was extended toward the semihydrogenation of
      internal alkynes. Under ambient temperatures and moderate pressures of H2, a
      broad scope of alkynes were semihydrogenated using a CoI-N2 precatalyst,
      resulting in the formation of trans-alkene products. Furthermore, mechanistic
      studies using 1H, 2H, and para-hydrogen induced polarization (PHIP) transfer NMR
      spectroscopy revealed cis-hydrogenation of the alkyne occurs first. The Co
      mediated alkene isomerization afforded the E-selective products from a broad
      group of alkynes with good yields and E/Z selectivity.

PMID- 27709918
TI  - EFFECT OF COLD PLASMA TREATMENT ON THE FUNCTIONAL PROPERTIES OF FRESH-CUT APPLES.
AB  - The atmospheric double barrier discharge (DBD) plasma technology is a promising
      tool in food industry as an alternative to traditional food preservation methods.
      However, the effect of the reactive chemical species generated during the
      treatment on the qualitative and quantitative content of bioactive compounds in
      food is still little studied, as well as there are no data concerning potential
      deleterious effects of DBD treated foods on human cells. We measured antioxidants
      content and antioxidant capacity of DBD-treated minimally processed Pink Lady(r)
      apples in comparison with untreated matched samples. Moreover, we compared the
      effects of polyphenols extracts obtained from DBD-treated apples on cell
      viability, reactive oxygen species production and phase II enzyme activation. The
      results show that the plasma treatment causes a slight reduction of antioxidant
      content and antioxidant capacity. Noteworthy, apple treated polyphenols extracts
      do not reduce cell viability and do not suppress the beneficial physiological
      cell response to oxidative stress.

PMID- 27709919
TI  - Ultrafast Singlet Energy Transfer in Porphyrin Dyads.
AB  - A weakly fluorescent Pt-bridged dyad composed of zinc(II) porphyrin (Zn; donor)
      and free base (Fb; acceptor) has been designed and exhibits an ultrafast singlet
      energy transfer between porphyrins. The use of larger atoms within the central
      linker significantly increases the MO coupling between the two chromophores and
      inherently the electronic communication.

PMID- 27709920
TI  - Key residues involved in the interaction between Cydia pomonella pheromone
      binding protein 1 (CpomPBP1) and Codlemone.
AB  - Codlemone exhibited high affinity to CpomPBP1, studying their binding mode can
      provide insights into the rational design of active semiochemicals. Our findings
      suggested that residues including Phe12, Phe36, Trp37, Ile52, Ile 94, Ala115 and
      Phe118 were favorable to the binding of Codlemone to CpomPBP1, whereas residues
      providing unfavorable contributions like Ser56 were negative to the binding. Van
      der waals energy and electrostatic energy, mainly derived from the sidechains of
      favorable residues, contributed most in the formation and stability keeping of
      CpomPBP1-Codlemone complex. Of the residues involved in the interaction between
      CpomPBP1 and Codlemone, Phe12 and Trp37, whose mutation into Ala caused
      significant decrease of CpomPBP1 binding ability, were two key residues in
      determining the binding affinity of Codlemone to CpomPBP1. This study shed lights
      on discovering novel active semiochemicals as well as facilitating chemical
      modification of lead semiochemicals.

PMID- 27709921
TI  - Decay of Coliphages in Sewage-Contaminated Freshwater: Uncertainty and Seasonal
      Effects.
AB  - Understanding the fate of enteric viruses in water is vital for protection of
      water quality. However, the decay of enteric viruses is not well characterized,
      and its uncertainty has not been examined yet. In this study, the decay of
      coliphages, an indicator for enteric viruses, was investigated in situ under both
      sunlit and shaded conditions as well as in summer and winter. The decay rates of
      coliphages and their uncertainties were analyzed using a Bayesian approach. The
      results from the summer experiments revealed that the decay rates of somatic
      coliphages were significantly higher in sunlight (1.29 +/- 0.06 day-1) than in
      shade (0.96 +/- 0.04 day-1), but the decay rates of male-specific (F+) coliphages
      were not significantly different between sunlight (1.09 +/- 0.09 day-1) and
      shaded treatments (1.11 +/- 0.08 day-1). The decay rates of both F+ coliphages
      (0.25 +/- 0.02 day-1) and somatic coliphages (0.12 +/- 0.01 day-1) in winter were
      considerably lower than those in summer. Temperature and chlorophyll a (chla)
      concentration varied significantly (p < 0.001) between the two seasons,
      suggesting that these parameters might be important contributors to the seasonal
      variation of coliphage decay. Additionally, the Bayesian approach provided full
      distributions of decay rates and reduced the uncertainty, offering useful
      information for comparing decay rates under different conditions.

PMID- 27709922
TI  - Enantioselective, Catalytic Fluorolactonization Reactions with a Nucleophilic
      Fluoride Source.
AB  - The enantioselective synthesis of 4-fluoroisochromanones via chiral aryl iodide
      catalyzed fluorolactonization is reported. This methodology uses HF*pyridine as a
      nucleophilic fluoride source with a peracid stoichiometric oxidant, and provides
      access to lactones containing fluorine-bearing stereogenic centers in high
      enantio- and diastereoselectivity. The regioselectivity observed in these
      lactonization reactions is complementary to that obtained with established
      asymmetric electrophilic fluorination protocols.

PMID- 27709923
TI  - Nonstoichiometric Adduct Approach for High-Efficiency Perovskite Solar Cells.
AB  - Since the groundbreaking report on a solid-state perovskite solar cell employing
      a methylammonium lead iodide-sensitized mesoporous TiO2 film and an organic hole
      conducting layer in 2012 by our group, the swift surge of perovskite
      photovoltaics opens a new paradigm in solar-cell research. As a result, ca. 1300
      peer-reviewed research articles were published in 2015. In this Inorganic
      Chemistry Forum on Halide Perovskite, the researches with highlights of work on
      perovskite solar cells in my laboratory are reviewed. We have developed a size
      controllable two-step spin-coating method and found that minimal nonradiative
      recombination in perovskite crystals could lead to high photovoltaic performance.
      A Lewis acid based adduct method and self-formed grain boundary process were
      developed for high-efficiency devices with reproducibility. A power conversion
      efficiency of 20.4% was achieved via grain boundary engineering based on a
      nonstoichiometric adduct approach. The incorporation of cesium in a formamidinium
      lead iodide perovskite was found to show better photostability and moisture
      stability. A reduction in the dimensionality from a three-dimensitonal
      nanocrystal to a one-dimensional nanowire led to a hypsochromic shift of
      absorption and fluorescence. To enhance the charge-carrier transport and light
      harvesting efficiency, a nanoarchitecture of oxide layers was proposed.

PMID- 27709924
TI  - Torsional Constraints of DNA Substrates Impact Cas9 Cleavage.
AB  - To examine the effect of the torsional constraints imposed on DNA substrates on
      Cas9 cleavage, we prepared con-strained DNA substrates using a DNA origami frame.
      By fixing the dsDNA at the connectors of the DNA frame, we created four different
      dsDNA substrates containing torsion-ally constrained or relaxed strands. We
      quantified the cleav-age of constrained and relaxed substrates by Cas9 with
      quantitative PCR. Moreover, we observed the Cas9/sgRNA complex bound to the DNA
      substrates and characterized the dissociation of the complex with high-speed AFM.
      The results revealed that the constrained non-target strand re-duced the cleavage
      efficiency of Cas9 drastically, whereas torsional constraints on the target
      strand had little effect on the cleavage. The present study suggests that highly
      ordered and constrained DNA structures could be obstacles for Cas9 and
      additionally provides insights in Cas9 dissociation at a single molecule level.

PMID- 27709926
TI  - Exploring the Chemical Reactivity between Carbon Dioxide and Three Transition
      Metals (Au, Pt, and Re) at High-Pressure, High-Temperature Conditions.
AB  - The role of carbon dioxide, CO2, as oxidizing agent at high pressures and
      temperatures is evaluated by studying its chemical reactivity with three
      transition metals: Au, Pt, and Re. We report systematic X-ray diffraction
      measurements up to 48 GPa and 2400 K using synchrotron radiation and laser
      heating diamond-anvil cells. No evidence of reaction was found in Au and Pt
      samples in this pressure-temperature range. In the Re + CO2 system, however, a
      strongly-driven redox reaction occurs at P > 8 GPa and T > 1500 K, and
      orthorhombic beta-ReO2 is formed. This rhenium oxide phase is stable at least up
      to 48 GPa and 2400 K and was recovered at ambient conditions. Raman spectroscopy
      data confirm graphite as a reaction product. Ab-initio total-energy structural
      and compressibility data of the beta-ReO2 phase shows an excellent agreement with
      experiments, altogether accurately confirming CO2 reduction P-T conditions in the
      presence of rhenium metal and the beta-ReO2 equation of state.

PMID- 27709925
TI  - Single Molecule Nanospectroscopy Visualizes Proton-Transfer Processes within a
      Zeolite Crystal.
AB  - Visualizing proton-transfer processes at the nanoscale is essential for
      understanding the reactivity of zeolite-based catalyst materials. In this work,
      the Bronsted-acid-catalyzed oligomerization of styrene derivatives was used for
      the first time as a single molecule probe reaction to study the reactivity of
      individual zeolite H-ZSM-5 crystals in different zeolite framework, reactant and
      solvent environments. This was accomplished via the formation of distinct dimeric
      and trimeric fluorescent carbocations, characterized by their different
      photostability, as detected by single molecule fluorescence microscopy. The
      oligomerization kinetics turned out to be very sensitive to the reaction
      conditions and the presence of the local structural defects in zeolite H-ZSM-5
      crystals. The remarkably photostable trimeric carbocations were found to be
      formed predominantly near defect-rich crystalline regions. This spectroscopic
      marker offers clear prospects for nanoscale quality control of zeolite-based
      materials. Interestingly, replacing n-heptane with 1-butanol as a solvent led to
      a reactivity decrease of several orders and shorter survival times of fluorescent
      products due to the strong chemisorption of 1-butanol onto the Bronsted acid
      sites. A similar effect was achieved by changing the electrophilic character of
      the para-substituent of the styrene moiety. Based on the measured turnover rates
      we have established a quantitative, single turnover approach to evaluate
      substituent and solvent effects on the reactivity of individual zeolite H-ZSM-5
      crystals.

PMID- 27709927
TI  - Realizing High Figure of Merit in Phase-Separated Polycrystalline Sn1-xPbxSe.
AB  - Solid-state thermoelectric technology, interconverting heat to electrical energy,
      offers a promising solution for relaxing global energy problems. A high
      dimensionless figure of merit ZT is desirable for high-efficiency thermoelectric
      power generation. To date, thermoelectric materials research has focused on
      increasing the material's ZT. Here we first fabricated phase-separated Sn1-xPbxSe
      materials by hydrothermal synthesis. We demonstrate that the simultaneous
      optimization of the power factor and significant reduction in thermal
      conductivity can be achieved in the phase-separated Sn1-xPbxSe material. The
      introduction of the PbSe phase contributes to improvement of the electrical
      conductivity and power factor of the SnSe phase. Meanwhile, nanoscale
      precipitates and mesoscale grains define all-scale hierarchical architectures to
      scattering phonons, leading to low lattice thermal conductivity. These two
      favorable factors lead to remarkably high thermoelectric performance with ZT ~
      1.7 at 873 K in polycrystalline SnSe + 1% PbSe along the pressing direction,
      which is a record-high ZT for SnSe polycrystals. These findings highlight the
      prospects of realizing highly effective solid-state thermoelectric devices.

PMID- 27709928
TI  - Stereoretentive Deuteration of alpha-Chiral Amines with D2O.
AB  - We present the direct and stereoretentive deuteration of primary amines using Ru
      bMepi (bMepi = 1,3-(6'-methyl-2'-pyridylimino)isoindolate) complexes and D2O.
      High deuterium incorporation occurs at the alpha-carbon (70-99%). For alpha
      chiral amines, complete retention of stereochemistry is achieved when using an
      electron-deficient Ru catalyst. The retention of enantiomeric purity is
      attributed to a high binding affinity of an imine intermediate with ruthenium, as
      well as to a fast H/D exchange relative to ligand dissociation.

PMID- 27709929
TI  - Analysis of Mycotoxins in Beer Using a Portable Nanostructured Imaging Surface
      Plasmon Resonance Biosensor.
AB  - A competitive inhibition immunoassay is described for the mycotoxins
      deoxynivalenol (DON) and ochratoxin A (OTA) in beer using a portable
      nanostructured imaging surface plasmon resonance (iSPR) biosensor, also referred
      to as imaging nanoplasmonics. The toxins were directly and covalently immobilized
      on a 3-dimensional carboxymethylated dextran (CMD) layer on a nanostructured iSPR
      chip. The assay is based on competition between the immobilized mycotoxins and
      free mycotoxins in the solution for binding to specific antibodies. The chip
      surface was regenerated after each cycle, and the combination of CMD and direct
      immobilization of toxins allowed the chips to be used for more than 450 cycles.
      The limits of detection (LODs) in beer were 17 ng/mL for DON and 7 ng/mL for OTA
      (or 0.09 ng/mL after 75 times enrichment). These LODs allowed detection of even
      less than 10% depletion of the tolerable daily intake of DON and OTA by beer.
      Significant cross-reactivity of anti-DON was observed toward DON-3-glucoside and
      3-acetyl-DON, while no cross-reactivity was seen for 15-acetyl-DON. A preliminary
      in-house validation with 20 different batches of beer showed that both toxins can
      be detected at the considered theoretical safe level for beer. The assay can be
      used for in-field or at-line detection of DON in beer and also in barley without
      preconcentration, while OTA in beer requires an additional enrichment step, thus
      making the latter in its present form less suitable for field applications.

PMID- 27709930
TI  - A Least-Squares Commutator in the Iterative Subspace Method for Accelerating Self
      Consistent Field Convergence.
AB  - A least-squares commutator in the iterative subspace (LCIIS) approach is explored
      for accelerating self-consistent field (SCF) calculations. LCIIS is similar to
      direct inversion of the iterative subspace (DIIS) methods in that the next
      iterate of the density matrix is obtained as a linear combination of past
      iterates. However, whereas DIIS methods find the linear combination by minimizing
      a sum of error vectors, LCIIS minimizes the Frobenius norm of the commutator
      between the density matrix and the Fock matrix. This minimization leads to a
      quartic problem that can be solved iteratively through a constrained Newton's
      method. The relationship between LCIIS and DIIS is discussed. Numerical
      experiments suggest that LCIIS leads to faster convergence than other SCF
      convergence accelerating methods in a statistically significant sense, and in a
      number of cases LCIIS leads to stable SCF solutions that are not found by other
      methods. The computational cost involved in solving the quartic minimization
      problem is small compared to the typical cost of SCF iterations and the approach
      is easily integrated into existing codes. LCIIS can therefore serve as a powerful
      addition to SCF convergence accelerating methods in computational quantum
      chemistry packages.

PMID- 27709931
TI  - The Effect of Economic Growth, Urbanization, and Industrialization on Fine
      Particulate Matter (PM2.5) Concentrations in China.
AB  - Rapid economic growth, industrialization, and urbanization in China have led to
      extremely severe air pollution that causes increasing negative effects on human
      health, visibility, and climate change. However, the influence mechanisms of
      these anthropogenic factors on fine particulate matter (PM2.5) concentrations are
      poorly understood. In this study, we combined panel data and econometric methods
      to investigate the main anthropogenic factors that contribute to increasing PM2.5
      concentrations in China at the prefecture level from 1999 to 2011. The results
      showed that PM2.5 concentrations and three anthropogenic factors were
      cointegrated. The panel Fully Modified Least Squares and panel Granger causality
      test results indicated that economic growth, industrialization, and urbanization
      increased PM2.5 concentrations in the long run. The results implied that if China
      persists in its current development pattern, economic growth, industrialization
      and urbanization will inevitably lead to increased PM2.5 emissions in the long
      term. Industrialization was the principal factor that affected PM2.5
      concentrations for the total panel, the industry-oriented panel and the service
      oriented panel. PM2.5 concentrations can be reduced at the cost of short-term
      economic growth and industrialization. However, reducing the urbanization level
      is not an efficient way to decrease PM2.5 pollutions in the short term. The
      findings also suggest that a rapid reduction of PM2.5 concentrations relying
      solely on adjusting these anthropogenic factors is difficult in a short-term for
      the heavily PM2.5-polluted panel. Moreover, the Chinese government will have to
      seek much broader policies that favor a decoupling of these coupling
      relationships.

PMID- 27709932
TI  - Azole Functionalized Polyoxo-Titanium Clusters with Sunlight-Driven Dye
      Degradation Applications: Synthesis, Structure, and Photocatalytic Studies.
AB  - Six polyoxo-titanium clusters (PTCs) with varying nuclearities containing Ti-N
      bonds and heteronuclearity, namely, [Ti6(MU3-O)2(MU2-O)2(O3P-Phen)2(OiPr)10(1
      hbta)2] (PTC-37), Ti8(MU3-O)2(MU2-O)2(O3P-Phen)2(OiPr)16(adn)2(NO3)2] (PTC-38),
      [Ti4(MU3-O)(MU2-O)(MU2-OiPr)2(OiPr)4(O3P-Phen)3(1,10-phn)](HOiPr) (PTC-39),
      [Ti4(MU3-O)(MU2-OiPr)3(OiPr)5(O3P-Phen)3(Im)] (PTC-40), [Ti4(MU3-O)(MU2
      OiPr)3(OiPr)5(O3P-Phen)3(Im)][Ti3M(MU3-O)(MU2-OiPr)3(OiPr)3(O3P-Phen)3(Im)] (M =
      Co for PTC-41 and M = Zn for PTC-42; O3P-Phen = phenyl phosphonate, 1-hbta = 1
      hydroxy benzotriazolate, adn = adenine, 1,10-phn = 1,10-phenanthroline, Im =
      imidazolate, and OiPr = isopropoxide) were prepared as crystalline samples and
      structurally characterized. Simultaneous doping of nitrogen and transition metal
      heteroatoms into the Ti-O clusters created complex chemical environments in the
      resulting hybrid materials. Thus, photocatalytic methylene blue degradation
      studies were performed to understand structure-property relationships in these Ti
      cluster-based materials. The complex chemical environment created in these novel
      molecular clusters had proved to exhibit ligand-dependent photocatalytic
      activities under normal sunlight. Adenine-functionalized PTC-38 presented
      moderate activities, while other PTCs all show rapid dye degradation.

PMID- 27709933
TI  - "On Water" C(sp3)-H Functionalization/C-O/C-N Bonds Formations: Synthesis of
      Functionalized Oxazolidines and Imidazolidines.
AB  - On water oxidative C(sp3)-H functionalization/C-O/C-N bonds formations using
      tetrabutylammonium iodide as the catalyst and tert-butyl hydroperoxide in water
      (T-Hydro) as the oxidant affords a potential route for the construction of
      functionalized oxazolidines and imidazolidines. The reaction is simple,
      regioselective, and effective at moderate temperature with broad substrate scope.
      In the case of optically active substrates, the oxidative cyclization can be
      accomplished with high optical purities.

PMID- 27709934
TI  - Fluorescent Base Analogue Reveals T-HgII-T Base Pairs Have High Kinetic
      Stabilities That Perturb DNA Metabolism.
AB  - The thymidine analogue DMAT was used for the first fluorescence-based study of
      direct, site-specific metal binding reactions involving unmodified nucleobases in
      duplex DNA. The fluorescence properties of DMAT-A base pairs were highly
      sensitive to mercury binding reactions at T-T mismatches located at an adjacent
      site or one base pair away. This allowed for precise determination of the local
      kinetic and thermodynamic parameters of T-HgII-T binding reactions. The on- and
      off-rates of HgII were surprisingly slow, with association rate constants (kon) ~
      104-105 M-1 s-1, and dissociation rate constants (koff) ~ 10-4-10-3 s-1; giving
      equilibrium dissociation constants (Kd) = 8-50 nM. In contrast, duplexes lacking
      a T-T mismatch exhibited local, nonspecific HgII binding affinities in the range
      of Kd = 0.2-2.0 MUM, depending on the buffer conditions. The exceptionally high
      kinetic stabilities of T-HgII-T metallo-base pairs (half-lives = 0.3-1.3 h)
      perturbed dynamic processes including DNA strand displacement and primer
      extension by DNA polymerases that resulted in premature chain termination of DNA
      synthesis. In addition to providing the first detailed kinetic and thermodynamic
      parameters of site-specific T-HgII-T binding reactions in duplex DNA, these
      results demonstrate that T-HgII-T base pairs have a high potential to disrupt DNA
      metabolism in vivo.

PMID- 27709936
TI  - One-Shot Determination of Residual Dipolar Couplings: Application to the
      Structural Discrimination of Small Molecules Containing Multiple Stereocenters.
AB  - A novel approach for the fast and efficient structural discrimination of
      molecules containing multiple stereochemical centers is described. A robust J
      resolved HSQC experiment affording highly resolved 1JCH/1TCH splittings along the
      indirect dimension and homodecoupled 1H signals in the detected dimension is
      proposed. The experiment enables in situ distinction of both isotropic and
      anisotropic components of molecules dissolved in compressed PMMA gels, allowing a
      rapid and direct one-shot determination of accurate residual dipolar coupling
      constants from a single NMR spectrum.

PMID- 27709935
TI  - Conserved Mechanism of Conformational Stability and Dynamics in G-Protein-Coupled
      Receptors.
AB  - G-protein-coupled receptors (GPCRs) are transmembrane receptors involved in
      diverse biological functions. Despite the diversity in their amino acid
      sequences, class A GPCRs exhibit a conserved structural topology and possibly a
      common mechanism of receptor activation. To understand how this high sequence
      diversity translates to a conserved functional mechanism, we have compared the
      dynamic behavior of eight class A GPCRs comprised of six biogenic amine
      receptors, adenosine A2A, and the peptide receptor protease-activated receptor 1.
      Starting from the crystal structures of the inactive state of these receptors
      bound to inverse agonists or antagonists, we have performed multiple all-atom MD
      simulations adding up to several microseconds of simulation. We elucidated the
      similarities and differences in the dynamic behavior and the conformational
      ensembles sampled by these eight class A GPCRs. Among the six biogenic amine
      receptors studied here, beta2-adrenergic receptor shows the highest level of
      fluctuation in the sixth and seventh transmembrane helices, possibly explaining
      its high basal activity. In contrast, the muscarinic acetylcholine receptors show
      the lowest fluctuations as well as tight packing and low hydration of the
      transmembrane domain. All eight GPCRs show several conserved allosteric
      communication pipelines from the residues in the agonist binding site with the G
      protein interface. Positions of the residues along these pipelines that serve as
      major hubs of allosteric communication are conserved in their respective
      structures. These findings have important implications in understanding the
      dynamics and allosteric mechanism of communication in class A GPCRs and hence are
      useful for designing conformation-specific drugs.

PMID- 27709937
TI  - Synthesis and Evaluation of QS-21-Based Immunoadjuvants with a Terminal
      Functionalized Side Chain Incorporated in the West Wing Trisaccharide.
AB  - Three QS-21-based vaccine adjuvant candidates with a terminal-functionalized side
      chain incorporated in the west wing trisaccharide have been synthesized. The
      terminal polar functional group serves to increase the solubility of these
      analogues in water. Two of the synthetic analogues have been shown to have
      adjuvant activity comparable to that of GPI-0100. The stand-alone adjuvant
      activity of the new synthetic analogues again confirmed that it is a feasible way
      to develop new saponin-based vaccine adjuvants through derivatizing at the west
      wing branched trisaccharide domain. Inclusion of an additional polar functional
      group such as a carboxyl group (as in 3x) or a monosaccharide (as in 4x and 5x)
      is sufficient to increase the water solubility of the corresponding synthetic
      analogues to a level comparable to that of GPI-0100 and suitable for
      immunological studies and clinical application. The structure of the incorporated
      side chain has a significant impact on the adjuvant activity in terms of the
      magnitude and nature of the host's responses.

PMID- 27709938
TI  - Additions of Thiols to 7-Vinyl-7-deazaadenine Nucleosides and Nucleotides.
      Synthesis of Hydrophobic Derivatives of 2'-Deoxyadenosine, dATP and DNA.
AB  - Additions of alkyl- or arylthiols to 7-vinyl-7-deaza-2'-deoxyadenosine gave a
      series of 7-[2-(alkyl- or arylsulfanyl)ethyl]-7-deaza-2'-deoxyadenosines in 45
      85% yields. The nucleosides were converted to 5'-O-mono-(dASRMP) or triphosphates
      (dASRTP) by phosphorylation. The modified triphosphates were also prepared by
      thiol addition to 7-vinyl-7-deaza-dATP. The triphosphates dASRTP were good
      substrates for DNA polymerases useful in the enzymatic synthesis of base-modified
      oligonucleotides (ONs) or DNA containing flexibly linked hydrophobic substituents
      in the major groove. Primer extension was used for the synthesis of ONs with one
      or several modifications, PCR was used for the synthesis of heavily modified DNA,
      whereas terminal deoxynucleotidyl transferase was used for a single-nucleotide
      labeling of the 3'-end.

PMID- 27709939
TI  - Assessing Ion-Water Interactions in the AMOEBA Force Field Using Energy
      Decomposition Analysis of Electronic Structure Calculations.
AB  - AMOEBA is a molecular mechanics force field that addresses some of the
      shortcomings of a fixed partial charge model, by including permanent atomic point
      multipoles through quadrupoles, as well as many-body polarization through the use
      of point inducible dipoles. In this work, we investigate how well AMOEBA
      formulates its non-bonded interactions, and how it implicitly incorporates
      quantum mechanical effects such as charge penetration (CP) and charge transfer
      (CT), for water-water and water-ion interactions. We find that AMOEBA's total
      interaction energies, as a function of distance and over angular scans for the
      water dimer and for a range of water-monovalent cations, agree well with an
      advanced density functional theory (DFT) model, whereas the water-halides and
      water-divalent cations show significant disagreement with the DFT result,
      especially in the compressed region when the two fragments overlap. We use a
      second-generation energy decomposition analysis (EDA) scheme based on absolutely
      localized molecular orbitals (ALMOs) to show that in the best cases AMOEBA relies
      on cancellation of errors by softening of the van der Waals (vdW) wall to balance
      permanent electrostatics that are too unfavorable, thereby compensating for the
      missing CP effect. CT, as another important stabilizing effect not explicitly
      taken into account in AMOEBA, is also found to be incorporated by the softened
      vdW interaction. For the water-halides and water-divalent cations, this
      compensatory approach is not as well executed by AMOEBA over all distances and
      angles, wherein permanent electrostatics remains too unfavorable and polarization
      is overdamped in the former while overestimated in the latter. We conclude that
      the DFT-based EDA approach can help refine a next-generation AMOEBA model that
      either realizes a better cancellation of errors for problematic cases like those
      illustrated here, or serves to guide the parametrization of explicit functional
      forms for short-range contributions from CP and/or CT.

PMID- 27709940
TI  - Synthesis of alpha-Quaternized 2,4-Cyclohexadienones from Propargyl Vinyl Ethers.
AB  - A microwave-assisted and base-catalyzed domino manifold to construct 2,4
      cyclohexadienone derivatives has been implemented. The domino manifold uses
      easily accessible tertiary propargyl vinyl ethers bearing a methine group at the
      homopropargylic position and imidazole as the catalyst to deliver 2,4
      cyclohexadienones featuring a key formyl group and a quaternized carbon atom in
      good yields.

PMID- 27709942
TI  - Photooxidation of Ditert-Butyl Malonate in the Presence and Absence of Nitrogen
      Dioxide.
AB  - The rate constant for the reaction of di-tert-butyl malonate (DTBM) with chlorine
      atoms in gas-phase was measured using cyclohexane and pentane as references. The
      measurements lead to a value of (1.5 ? 0.1) x 10-10 cm3 molecule-1 s-1. The
      subsequent photo-oxidation mechanism of DTBM in the absence and presence of
      nitrogen dioxide was investigated. The main carbonated products identified in the
      first case were acetone, formic acid, carbon monoxide, and carbon dioxide. The
      addition of nitrogen dioxide lead besides to the formation of (CH3)3CC(O)OONO2
      and (CH3)3CONO2. The proposed photo-oxidation mechanism was supported both
      experimentally and by computational calculations. The results reveal that the
      (CH3)3COC(O)CH2C(O)OC(CH3)2O* radical formed reacts according to two competitive
      reactions: decomposition to yield acetone and (CH3)3COC(O)CH2C(O)O* radical (55
      +/- 2) %, and migration of the H-atom of the methylene group to the terminal
      oxygen atom (40 +/- 3) %.

PMID- 27709941
TI  - 1-Hydroxybenzotriazole-Assisted, N-Heterocyclic Carbene Catalyzed beta
      Functionalization of Saturated Carboxylic Esters: Access to Spirooxindole
      Lactones.
AB  - A 1-hydroxybenzotriazole-assisted, N-heterocyclic carbene catalyzed direct beta
      functionalization of saturated carboxylic esters is disclosed. This formal [3 +
      2] annulation reaction of carboxylic esters with isatins affords optically pure
      spirooxindole lactones (on gram scale) bearing two vicinal stereogenic centers. A
      dual role of HOBt is proposed based on controlled experiments to rationalize the
      enhancement of diastereoselectivity and enantioselectivity.

PMID- 27709943
TI  - Diastereoselective Radical Hydrogen Transfer Reactions using N-Heterocyclic
      Carbene Boranes.
AB  - Reported herein are the first diastereoselective and Lewis acid-mediated radical
      reactions of N-heterocyclic carbene (NHC) boranes. We applied these reactions to
      the synthesis of four propionate diastereoisomers combining an aldol reaction,
      followed by a stereoselective radical-based reduction in which the NHC borane
      serves as the hydrogen donor, thus obviating the use of tin-based reagents. The
      2,3-syn isomer is obtained by combining an NHC-borane and a Lewis acid
      (MgBr2.OEt2), while using a reverse polarity strategy provides the 2,3-anti
      isomer.

PMID- 27709944
TI  - Correlation Effects in Scanning Tunneling Microscopy Images of Molecules Revealed
      by Quantum Monte Carlo.
AB  - Scanning tunneling microscopy (STM) and spectroscopy probe the local density of
      states of single molecules electrically insulated from the substrate. The
      experimental images, although usually interpreted in terms of single-particle
      molecular orbitals, are associated with quasiparticle wave functions dressed by
      the whole electron-electron interaction. Here we propose an ab initio approach
      based on quantum Monte Carlo to calculate the quasiparticle wave functions of
      molecules. Through the comparison between Monte Carlo wave functions and their
      uncorrelated Hartree-Fock counterparts we visualize the electronic correlation
      embedded in the simulated STM images, highlighting the many-body features that
      might be observed.

PMID- 27709946
TI  - Conjugated Thiophene-Fused Isatin Dyes through Intramolecular Direct Arylation.
AB  - We report on the design, synthesis, and properties of innovative, planar, pi
      conjugated compounds in which a thiophene ring is fused with the skeleton of the
      naturally occurring dye isatin. The synthesis is achieved in high yields making
      use of an intramolecular direct arylation reaction as the key step, making the
      overall process potentially scalable. The synthetic sequence has been
      demonstrated also for an isatin bearing fluorine substituents on the aromatic
      ring. NMR and X-ray studies demonstrate the crosstalk occurring between the
      fused, coplanar, and conjugated moieties, making these novel dyes with a donor
      acceptor character. Cyclic voltammetry and UV-vis studies confirm very
      interesting HOMO-LUMO levels and energy gaps for the new compounds.

PMID- 27709945
TI  - Design, Synthesis, and Biological Evaluation of Novel Tetrahydroprotoberberine
      Derivatives (THPBs) as Selective alpha1A-Adrenoceptor Antagonists.
AB  - A novel series of tetrahydroprotoberberine derivatives (THPBs) were designed,
      synthesized, and evaluated as selective alpha1A-adrenergic receptors (AR)
      antagonists for the treatment of benign prostatic hyperplasia. On the basis of
      the pharmacophore model of the marketed drug silodosin, THPBs were modified by
      introducing an indole segment into their core scaffolds. In calcium assays, 7 out
      of 32 compounds displayed excellent antagonistic activities against alpha1A-ARs,
      with IC50 less than 250 nM. Among them, compound (S)-27 had the most potent
      biological activity; its IC50 toward alpha1A-AR was 12.8 +/- 2.2 nM, which is 781
      and 20 times more selective than that toward alpha1B- and alpha1D-AR,
      respectively. In the functional assay using isolated rat tissues, compound (S)-27
      inhibited norepinephrine-induced urethra smooth muscle contraction potently (IC50
      = 0.5 +/- 0.3 nM), without inhibiting the aortic contraction (IC50 > 1000 nM),
      displaying a better tissue selectivity than the marketed drug silodosin.
      Additional results of preliminary safety studies (acute toxicity and hERG
      inhibition) and pharmacokinetics studies indicated the potential druggability for
      compound (S)-27 which is a promising lead for the development of selective
      alpha1A-AR antagonists for the treatment of BPH.

PMID- 27709947
TI  - Cp*Co(III)-Catalyzed C-H/N-N Functionalization of Arylhydrazones for the
      Synthesis of Isoquinolines.
AB  - Cationic Co(III)-catalyzed C-H/N-N bond functionalization of arylhydrazones with
      internal alkynes has been developed for the synthesis of isoquinoline
      derivatives. The arylhydrazones are easy to prepare and require inexpensive and
      commercially available hydrazine hydrate. The reaction works well with a variety
      of internal alkynes and arylhydrazones and offers broad scope, good functional
      group tolerance, and high yields under redox-neutral conditions in the presence
      of air.

PMID- 27709948
TI  - Structures and Acidity Constants of Silver-Sulfide Complexes in Hydrothermal
      Fluids: A First Principles Molecular Dynamics Study.
AB  - In order to quantify the speciation and structures of silver-sulfide complexes in
      aqueous solutions, we have carried out systematic first principles molecular
      dynamics (FPMD) simulations at three temperatures (25 degrees C, 200 degrees C,
      and 300 degrees C). It is found that mono-sulfide (i.e., Ag(HS)) and di-sulfide
      species (i.e., Ag(HS)2-) are the major silver-sulfide species over a wide T-P
      range, while Ag(HS)32- can hold stably only at ambient temperatures and Ag(HS)43-
      does not exist even at the ambient conditions. Ag(H2S)+ has a tetrahedral
      structure up to 300 degrees C (i.e., Ag(H2S)(H2O)3+). Ag(H2S)2+ remains 4
      coordinated to 200 degrees C (i.e., Ag(H2S)2(H2O)2+) but it transforms to 3
      coordinate at 300 degrees C (i.e., Ag(H2S)2(H2O)+). All of the other mono- and di
      sulfide species (Ag(HS)(H2O)0, Ag(HS)(OH)-, Ag(HS)(H2S)0, Ag(HS)2- and AgS(HS)2-)
      have two-fold linear structures. For their solvation structures, the H2S ligands
      donate weak H-bonds to water O; the HS- ligands accept weak H-bonds from water H;
      the dangling S2- form strong H-bonds with H of water molecules and the OH-
      ligands can form strong H-bonds as donors and weak H-bonds as acceptors. We
      further calculated the acidity constants (i.e. pKas) of Ag(H2S)+ and Ag(H2S)2+
      complexes using FPMD based vertical energy gap method. Based on the calculated
      pKas, the mono- and di-sulfide species distributions versus pH have been derived.
      We found that for mono-sulfide species, Ag(HS)(H2O)0 is the major species in near
      neutral pH, while Ag(H2S)(H2O)3+ and Ag(HS)(OH)- exist in the acid and alkaline
      pH range at T<=200 degrees C, respectively. At 300 degrees C, both Ag(HS)(OH)-
      and Ag(HS)(H2O)0 are dominant in the neutral pH range, and Ag(H2S)(H2O)2+ only
      exists in acidic solutions. For di-sulfide species, Ag(HS)2- is dominative in
      near neutral pH condition at the three temperatures; Ag(HS)(H2S)0 stays in mild
      acidic pH range only at 25 degrees C; AgS(HS)2- and Ag(H2S)2(H2O)2+
      (Ag(H2S)2(H2O)+ at 300 degrees C) are trivial at the three conditions. The
      results of structures and acidity constants provide quantitative and microscopic
      basis for understanding the behavior of silver complexes in hydrothermal fluids.

PMID- 27709949
TI  - Systematic and Automated Development of Quantum Mechanically Derived Force
      Fields: The Challenging Case of Halogenated Hydrocarbons.
AB  - A robust and automated protocol for the derivation of sound force field
      parameters, suitable for condensed-phase classical simulations, is here tested
      and validated on several halogenated hydrocarbons, a class of compounds for which
      standard force fields have often been reported to deliver rather inaccurate
      performances. The major strength of the proposed protocol is that all of the
      parameters are derived only from first principles because all of the information
      required is retrieved from quantum mechanical data, purposely computed for the
      investigated molecule. This a priori parametrization is carried out separately
      for the intra- and intermolecular contributions to the force fields, respectively
      exploiting the Joyce and Picky programs, previously developed in our group. To
      avoid high computational costs, all quantum mechanical calculations were
      performed exploiting the density functional theory. Because the choice of the
      functional is known to be crucial for the description of the intermolecular
      interactions, a specific procedure is proposed, which allows for a reliable
      benchmark of different functionals against higher-level data. The intramolecular
      and intermolecular contribution are eventually joined together, and the resulting
      quantum mechanically derived force field is thereafter employed in lengthy
      molecular dynamics simulations to compute several thermodynamic properties that
      characterize the resulting bulk phase. The accuracy of the proposed
      parametrization protocol is finally validated by comparing the computed
      macroscopic observables with the available experimental counterparts. It is found
      that, on average, the proposed approach is capable of yielding a consistent
      description of the investigated set, often outperforming the literature standard
      force fields, or at least delivering results of similar accuracy.

PMID- 27709950
TI  - Ligand NMR Chemical Shift Calculations for Paramagnetic Metal Complexes: 5f1 vs
      5f2 Actinides.
AB  - Ligand paramagnetic NMR (pNMR) chemical shifts of the 5f1 complexes UO2(CO3)35-
      and NpO2(CO3)34-, and of the 5f2 complexes PuO2(CO3)34- and (C5H5)3UCH3 are
      investigated by wave function theory calculations, using a recently developed sum
      over-states approach within complete active space and restricted active space
      paradigm including spin-orbit (SO) coupling [J. Phys. Chem. Lett. 2015, 20, 2183
      2188]. The experimental 13C pNMR shifts of the actinyl tris-carbonate complexes
      are well reproduced by the calculations. The results are rationalized by
      visualizing natural spin orbitals (NSOs) and spin-magnetizations generated from
      the SO wave functions, in comparison with scalar relativistic spin densities. The
      analysis reveals a complex balance between spin-polarization, spin and orbital
      magnetization delocalization, and spin-compensation effects due to SO coupling.
      This balance creates the magnetization due to the electron paramagnetism around
      the nucleus of interest, and therefore the pNMR effects. The calculated proton
      pNMR shifts of the (C5H5)3UCH3 complex are also in good agreement with
      experimental data. Because of the nonmagnetic ground state of (C5H5)3UCH3, the 1H
      pNMR shifts arise mainly from the magnetic coupling contributions between the
      ground state and low-energy excited states belonging to the 5f manifold, along
      with the thermal population of degenerate excited states at ambient temperatures.

PMID- 27709951
TI  - Minimal Self-Immolative Probe for Multimodal Fluoride Detection.
AB  - Two single-molecule, self-immolative fluoride probes, namely tert
      butyldimethylsilyl-protected 2- and 4-difluoromethylphenol, are described.
      Compared to similar systems previously described, the probes are characterized by
      a simpler structure and straightforward, two-step preparation. Nevertheless, they
      allow the detection of fluoride ions at micromolar concentration by the naked
      eye, UV-vis absorption, and fluorescence. A detailed investigation of the self
      immolative reaction reveals that the rate-limiting step is the release of the
      first fluoride ion from the difluoromethylphenolate intermediate. Moreover, the
      mutual position of the difluoromethyl- and tert-butyldimethylsilyl-protected
      residues has a relevant effect on the reactivity. Likely, a CF2H-O hydrogen bond
      in the 2-isomer increases the reactivity of the silyl ether toward hydrolytic
      cleavage but also stabilizes the phenolate intermediate, slowing the release of
      fluoride ions.

PMID- 27709952
TI  - Modulation of the Excited-State Dynamics of 2,2'-Bipyridine-3,3'-diol in Crown
      Ethers: A Possible Way To Control the Morphology of a Glycine Fibril through
      Fluorescence Lifetime Imaging Microscopy.
AB  - In this article, we have investigated the modulation of excited-state
      intramolecular double proton transfer (ESIDPT) dynamics of 2,2'-bipyridine-3,3'
      diol (BP(OH)2) in two crown ethers (CEs), namely, 18-Crown-6 (18C6) and 15-Crown
      5 (15C5). From steady-state UV-visible measurements, we have shown that there is
      no significant interaction between the dienol tautomeric form of BP(OH)2 and two
      CEs. However, in the presence of CEs, an additional emission band (~415 nm) is
      generated along with the diketo tautomer band (~465 nm). In time-resolved
      analysis, we have observed the generation of ~260 ps rise component in the
      presence of 18C6. Therefore, by combining the results of steady-state and time
      resolved emissions, we have proposed that the water-assisted ESIDPT route of
      BP(OH)2 generates a hydronium ion (H3O+) in the excited state. 18C6 binds nicely
      to this H3O+ ion. As a result, retarded ESIDPT dynamics is observed in 18C6.
      However, as 15C5 cannot bind H3O+ properly, no rise component is found. With the
      addition of potassium chloride (KCl), the contribution of the rise component
      decreases due to unavailability of free 18C6 cavity to capture the H3O+ ion
      generated in the excited state. Addition of calcium chloride (CaCl2) leads to
      complete removal of the rise component due to the inhibition of the water
      assisted ESIDPT route. From wavelength-dependent behavior, we have observed that
      the rise component is present only at 465 nm in 18C6. We have also shown that the
      fibrillar morphology of glycine can be successfully probed through fluorescence
      lifetime imaging microscopy using BP(OH)2 as an imaging agent. Modulation of
      fibrillar morphology has been found in the presence of two CEs. The interaction
      of glycine fiber with CEs can be explained by lifetime distribution analysis.

PMID- 27709953
TI  - Thermal Response of Poly(N-isopropylacrylamide) Brushes Probed by Surface Plasmon
      Resonance.
AB  - The thermally induced hydration transition of surface-grafted poly(N-isopropyl
      acrylamide) (PNIPAAm) brushes was probed by surface plasmon resonance
      spectroscopy (SPR) and contact angle measurements. Data are presented for a
      PNIPAAm brush film with a dry thickness of ~50 nm that was synthesized by atom
      radical transfer polymerization on the surface of a self-assembled monolayer on
      gold. SPR measurements were taken as a function of temperature in two modes:  the
      quasi-static mode, in which the sample was equilibrated at each temperature for
      ~15 min prior to measurement, and the real-time mode, in which SPR reflectivity
      data were collected as the sample was heated and cooled at ~4.5  degrees C/min.
      Both types of measurement indicate that the hydration transition for the PNIPAAm
      brush occurs over a broad range of temperatures (~10-40  degrees C). This result
      is in accordance with theoretical predictions that have suggested that polymer
      brush structures on planar surfaces do not exhibit true critical solubility
      transitions. Contact angle measurements revealed a discontinuity in the surface
      wettability at a temperature (~32  degrees C) that corresponds to the dilute
      aqueous critical solution temperature. Taken together, these results suggest that
      the polymer segments in the outermost region of the brush remain highly solvated
      until the dilute solution lower critical solution temperature (~32 degrees ),
      while densely packed, less solvated segments within the brush layer undergo
      dehydration and collapse over a broad range of temperatures.

PMID- 27709954
TI  - Interfacial Stability of Li Metal-Solid Electrolyte Elucidated via in Situ
      Electron Microscopy.
AB  - Despite their different chemistries, novel energy-storage systems, e.g., Li-air,
      Li-S, all-solid-state Li batteries, etc., face one critical challenge of forming
      a conductive and stable interface between Li metal and a solid electrolyte. An
      accurate understanding of the formation mechanism and the exact structure and
      chemistry of the rarely existing benign interfaces, such as the Li-cubic-Li7
      3xAlxLa3Zr2O12 (c-LLZO) interface, is crucial for enabling the use of Li metal
      anodes. Due to spatial confinement and structural and chemical complications,
      current investigations are largely limited to theoretical calculations. Here,
      through an in situ formation of Li-c-LLZO interfaces inside an aberration
      corrected scanning transmission electron microscope, we successfully reveal the
      interfacial chemical and structural progression. Upon contact with Li metal, the
      LLZO surface is reduced, which is accompanied by the simultaneous implantation of
      Li+, resulting in a tetragonal-like LLZO interphase that stabilizes at an
      extremely small thickness of around five unit cells. This interphase effectively
      prevented further interfacial reactions without compromising the ionic
      conductivity. Although the cubic-to-tetragonal transition is typically undesired
      during LLZO synthesis, the similar structural change was found to be the likely
      key to the observed benign interface. These insights provide a new perspective
      for designing Li-solid electrolyte interfaces that can enable the use of Li metal
      anodes in next-generation batteries.

PMID- 27709955
TI  - Novel effects of compressed CO2 molecules on structural ordering and charge
      transport in conjugated poly(3-hexylthiophene) thin films.
AB  - We report the effects of compressed CO2 molecules as a novel plasticization agent
      for poly(3-hexylthiophene) (P3HT) conjugated polymer thin films. In-situ neutron
      reflectivity experiment demonstrated the excess sorption of CO2 molecules in the
      P3HT thin films (about 40 nm in thickness) at low pressure (P = 8.2 MPa) under
      the isothermal condition of T = 36  degrees C, which is far below the polymer
      bulk melting point. The results evidenced that these CO2 molecules accelerated
      the crystallization process of the polymer on the basis of ex-situ grazing
      incidence X-ray diffraction measurements after drying the films via rapid
      depressurization to atmospheric pressure: not only the out-of-plane lamellar
      ordering of the backbone chains but also intra-plane pi-pi stacking of the side
      chains were significantly improved, when compared to those in the control P3HT
      films subjected to conventional thermal annealing (at T = 170  degrees C).
      Electrical measurements elucidated that the CO2-annealed P3HT thin films
      exhibited enhanced charge carrier mobility along with decreased background charge
      carrier concentration and trap density compared to those in the thermally
      annealed counterpart. This is attributed to the CO2-induced increase in polymer
      chain mobility that can drive the detrapping of molecular oxygen and healing of
      conformational defects in the polymer thin film. Given the universality of the
      excess sorption of CO2 regardless of the type of polymers, the present findings
      suggest that the CO2 annealing near the critical point can be useful as a robust
      processing strategy for improving structural and electrical characteristics of
      other semiconducting conjugated polymers and related systems such as polymer:
      fullerene bulk heterojunction films.

PMID- 27709956
TI  - Modeling the Formation of Alkali Aluminosilicate Gels at the Mesoscale Using
      Coarse-Grained Monte Carlo.
AB  - Alkali-activated materials (AAMs) are currently being pursued as viable
      alternatives to conventional ordinary Portland cement because of their lower
      carbon footprint and established mechanical performance. However, our
      understanding of the mesoscale morphology (~1 to 100 nm) of AAMs and related
      amorphous aluminosilicate gels, including the development of the three
      dimensional aluminosilicate network and nanoscale porosity, is severely limited.
      This study investigates the structural changes that occur during the formation of
      AAM gels at the mesoscale by utilizing a coarse-grained Monte Carlo (CGMC)
      modeling technique that exploits density functional theory calculations. The
      model is capable of simulating the reaction of an aluminosilicate particle in a
      highly alkaline solution (sodium hydroxide or sodium silicate). Two precursor
      morphologies have been investigated (layered alumina and silica sheets mimicking
      metakaolin and spherical aluminosilicate particles reminiscent of coal-derived
      fly ash) to determine if the precursor morphology has an impact on the structural
      evolution of the resulting alkali-activated aluminosilicate gel. The CGMC model
      can capture the three major stages of the alkali-activation process-dissolution,
      polycondensation, and reorganization-revealing that the dissolved silicate and
      aluminate species, ranging from monomers to nanoprecipitates (100s of monomers in
      size), exist in the pore solution of the hardened gel. The model also reveals
      that the silica concentration of the activating solution controls the extent of
      dissolution of the precursor particle. From the analysis of the aluminosilicate
      cluster size distributions, the mechanisms of AAM gel growth have been
      elucidated, revealing that Ostwald ripening occurs in systems containing free
      silica at the start of the reaction. On the other hand, growth of the hydroxide
      activated systems (metakaolin and fly ash) occurs via the formation of
      intermediate-sized clusters in addition to continual growth of the largest
      particle. The simulation results indicate that the nature of the gel growth is
      not influenced by the precursor particle morphology.

PMID- 27709957
TI  - Colorimetry Technique for Scalable Characterization of Suspended Graphene.
AB  - Previous statistical studies on the mechanical properties of chemical-vapor
      deposited (CVD) suspended graphene membranes have been performed by means of
      measuring individual devices or with techniques that affect the material. Here,
      we present a colorimetry technique as a parallel, noninvasive, and affordable way
      of characterizing suspended graphene devices. We exploit Newton's rings
      interference patterns to study the deformation of a double-layer graphene drum
      13.2 MUm in diameter when a pressure step is applied. By studying the time
      evolution of the deformation, we find that filling the drum cavity with air is 2
      5 times slower than when it is purged.

PMID- 27709958
TI  - Early-Evaporation of Microlayer for Boiling Heat Transfer Enhancement.
AB  - For over five decades, enhancement in pool boiling heat transfer has been
      achieved by altering the surface wetting, wickability, roughness, nucleation site
      density and providing separate liquid/vapor pathways. In this work, a new
      enhancement mechanism based on the early-evaporation of the microlayer is
      discovered and validated. The microlayer is a thin liquid film present at the
      base of a vapor bubble. Presence of micro-ridges on the silicon-dioxide surface
      partitions the microlayer and disconnects it from bulk liquid causing it to
      evaporate sooner, thus leading to increase in bubble growth rate, heat transfer,
      departure frequency and critical heat flux (CHF). Compared to a plain surface,
      ~120% enhancement in CHF is obtained with only ~18% increase in surface area. A
      CHF enhancement map is developed based on ridge height and spacing, resulting in
      three regions of full, partial and no enhancement. The new mechanism is validated
      by comparing the growth rate of a laser created vapor bubble on ridge-structured
      surface and plain surface, and the corresponding prediction of CHF enhancement is
      found to be in good agreement with experimental boiling data. This discovery
      opens up a new field of CHF enhancement and can be coupled with existing
      techniques to further push the limits of boiling heat transfer.

PMID- 27709959
TI  - 64Cu2+ Ions as PET Probe: An Emerging Paradigm in Molecular Imaging of Cancer.
AB  - Positron emission tomography (PET) imaging has transformed diagnostic nuclear
      medicine and become an essential strategy in cancer management. With the expected
      growth of this molecular imaging modality, there is a recognized need for new PET
      probes to address the clinical challenges in the early diagnosis and staging of
      various types of cancers. In this endeavor, the prospect of using 64Cu in the
      form of simple Cu2+ ions as PET probe is not only a cost-effective proposition
      but also seems poised to broaden the palette of molecular imaging probes in the
      foreseeable future. The usefulness of 64Cu2+ ions as PET probe is based on the
      fact that Cu is an essential element that plays an important role in cell
      proliferation and angiogenesis. Over the past few years, there has been
      continuous flow of evidences based on studies in animal models on the uptake of
      64Cu2+ ions in different types of tumors, including, hepatoma, colorectal cancer,
      prostate cancer, lung cancer, breast cancer, head and neck cancer, fibrosarcoma,
      melanoma, glioblastoma, and ovarian cancer. The widespread preclinical success of
      64Cu2+ ions as PET probe has recently resulted in translation of this radiotracer
      to clinical settings for noninvasive imaging and staging of prostate cancer in
      human patients. In this concise review, we have focused on the latest
      developments in PET imaging of cancer in preclinical and clinical settings using
      64Cu2+ ion as a probe and discussed the challenges and opportunities for future
      development.

PMID- 27709961
TI  - N,N-Dimethylformamide as Hydride Source in Nickel-Catalyzed Asymmetric
      Hydrogenation of alpha,beta-Unsaturated Esters.
AB  - Asymmetric transfer hydrogenation of alpha,beta-unsaturated esters is realized by
      using a nickel/bisphosphine catalyst and N,N-dimethylformamide (DMF) as the
      hydride source.

PMID- 27709960
TI  - Ag(I)-Catalyzed Domino Cyclization-Addition Sequence with Simultaneous Carbonyl
      and Alkyne Activation as a Route to 2,2'-Disubstituted Bisindolylarylmethanes.
AB  - An efficient synthesis of symmetrical 3, 3'-bisindolylarylmethanes with various
      substituents on the indole moiety has been developed by Ag(I)-catalyzed
      cycloisomerization and an deoxygenative addition sequence on o-alkynylanilines
      and aryl aldehydes. Ag(I) is proposed to activate alkyne unit and carbonyl moiety
      simultaneously leading to a domino first 5-endo-dig indole annulation, addition
      to C?O, second indole annulation, and its dehydroxylative addition.

PMID- 27709962
TI  - Synthesis of Bifunctional Potassium Acyltrifluoroborates.
AB  - New bifunctional potassium acyltrifluoroborate (KAT) substrates have been
      synthesized in gram scale using optimized reaction conditions. Chemoselective
      transformation of functional groups in the presence of an acyltrifluoroborate has
      been demonstrated, and orthogonal reactions of bifunctional KAT reagents are
      reported. This allows for the incorporation of KAT moieties into peptides and
      dyes.

PMID- 27709963
TI  - Enantioselective Synthesis of 4- and 6-Azaindolines by a Cation-Directed
      Cyclization.
AB  - Functionalized 4- and 6-azaindolines are accessible with high levels of
      enantioselectivity by the cation-directed cyclization of aminopyridine-derived
      imines via phase-transfer catalysis. The extension of this methodology to
      diastereoselective cyclizations is also described.

PMID- 27709964
TI  - Series of Hydrated Heterometallic Uranyl-Cobalt(II) Coordination Polymers with
      Aromatic Polycarboxylate Ligands: Formation of U?O-Co Bonding upon Dehydration
      Process.
AB  - Five new heterometallic UO22+-Co2+ coordination polymers have been obtained by
      hydrothermal reactions of uranyl nitrate and metallic cobalt with aromatic
      polycarboxylic acids. Single-crystal X-ray diffraction reveals the formation of
      four 3D frameworks with the mellitate (noted mel) ligand and one 2D network with
      the isophthalate (noted iso) ligand. The compounds
      [(UO2(H2O))2Co(H2O)4(mel)].4H2O (1), [UO2Co(H2O)4(H2mel)].2H2O (2), and
      [(UO2(H2O))2Co(H2O)4(mel)] (4) consist of 3D frameworks built up from the
      connection of mellitate ligands and mononuclear metallic centers. These three
      compounds exhibit two types of geometry for the uranyl cation: pentagonal
      bipyramidal environment for 1 and 4, and hexagonal bipyramidal environment for 2.
      Using the mellitate ligand, the uranyl dinuclear unit is isolated in the compound
      [(UO2)2(OH)2(Co(H2O)4)2(mel)].2H2O (3). Due to their 2D framework and the
      presence of uncoordinated cobalt(II) cations, the compound
      [(UO2)(iso)3][Co(H2O)6].3(H2O) (5) is drastically different than the previous
      one. The thermal behavior of compounds 1, 2, and 3 has been studied by
      thermogravimetric analysis, X-ray thermodiffraction, and in situ infrared. By
      heating, the dehydration of compounds 1 and 2 promotes two structural transitions
      (1 -> 1' and 2 -> 2'). The crystal structures of [(UO2(H2O))2Co(H2O)2(mel)] (1')
      and [(UO2)Co(H2mel)] (2') were determined by single-crystal X-ray diffraction;
      each of them presents a heterometallic interaction between uranyl bond and the
      Co(II) center. Due to the rarely reported coordination environment for the cobalt
      center in compound 2' (square pyramidal configuration), the magnetic properties
      and EPR characterizations of the compounds 2 and 2' were also investigated.

PMID- 27709965
TI  - Elastocaloric Effect in Carbon Nanotubes and Graphene.
AB  - Carbon nanotubes are famous for their many extraordinary properties. We use a
      thermodynamical approach, experimental data from the literature, and atomistic
      simulations to reveal one more remarkable property of the carbon nanotubes that
      has so far been overlooked. Namely, we predict the existence of very large
      elastocaloric effect that can reach up to 30 K under moderate loads. Potentially
      even larger values could be achieved under extreme loads, putting carbon
      nanotubes in the forefront of caloric materials. Other remarkable features of the
      elastocaloric effect in carbon nanotubes include linearity of elastocaloric
      temperature change in applied force (compressive or stretching), very weak
      dependence on the temperature, and an absence of hysteresis. Such features are
      extremely desirable for practical applications in cooling devices. Moreover, a
      similarly large elastocaloric effect is predicted for the graphene. The
      prediction of a large elastocaloric effect in carbon nanotubes and graphene sets
      forward an unconventional strategy of targeting materials with moderate caloric
      responses but the ability to withstand very large loads.

PMID- 27709967
TI  - Correction to "A Concise Construction of the Chlorahololide Heptacyclic Core".

PMID- 27709968
TI  - Experimenter expectancy bias does not explain Eurasian jays' (Garrulus
      glandarius) performance in a desire-state attribution task.
AB  - Male Eurasian jays have been found to adjust the type of food they share with
      their female partner after seeing her eat 1 type of food to satiety. One
      interpretation of this behavior is that the male encoded the female's decreased
      desire for the food she was sated on, and adjusted his behavior accordingly.
      However, in these studies, the male's actions were scored by experimenters who
      knew on which food the female was sated. Thus, it is possible that the
      experimenters' expectations (subconsciously) affected their behavior during tests
      that, in turn, inadvertently could have influenced the males' actions. Here, we
      repeated the original test with an experimenter who was blind to the food on
      which the female was sated. This procedure yielded the same results as the
      original studies: The male shared food with the female that was in line with her
      current desire. Thus, our results rule out the possibility that the Eurasian jay
      males' actions in the food sharing task could be explained by the effects of an
      experimenter expectancy bias. (PsycINFO Database Record

PMID- 27709966
TI  - All-Atom Continuous Constant pH Molecular Dynamics With Particle Mesh Ewald and
      Titratable Water.
AB  - Development of a pH stat to properly control solution pH in biomolecular
      simulations has been a long-standing goal in the community. Toward this goal
      recent years have witnessed the emergence of the so-called constant pH molecular
      dynamics methods. However, the accuracy and generality of these methods have been
      hampered by the use of implicit-solvent models or truncation-based electrostatic
      schemes. Here we report the implementation of the particle mesh Ewald (PME)
      scheme into the all-atom continuous constant pH molecular dynamics (CpHMD)
      method, enabling CpHMD to be performed with a standard MD engine at a fractional
      added computational cost. We demonstrate the performance using pH replica
      exchange CpHMD simulations with titratable water for a stringent test set of
      proteins, HP36, BBL, HEWL, and SNase. With the sampling time of 10 ns per
      replica, most pKa's are converged, yielding the average absolute and root-mean
      square deviations of 0.61 and 0.77, respectively, from experiment. Linear
      regression of the calculated vs experimental pKa shifts gives a correlation
      coefficient of 0.79, a slope of 1, and an intercept near 0. Analysis reveals
      inadequate sampling of structure relaxation accompanying a protonation-state
      switch as a major source of the remaining errors, which are reduced as simulation
      prolongs. These data suggest PME-based CpHMD can be used as a general tool for pH
      controlled simulations of macromolecular systems in various environments,
      enabling atomic insights into pH-dependent phenomena involving not only soluble
      proteins but also transmembrane proteins, nucleic acids, surfactants, and
      polysaccharides.

PMID- 27709969
TI  - Anticipated ambiguity prolongs the present: Evidence of a return trip effect.
AB  - Every event that can occupy a span of time can also warp how long that duration
      feels. No shortage of factors configures such duration estimates, yet they remain
      largely confined to events experienced in the present moment. Might future events
      similarly impact duration? The present investigation leverages a phenomenological
      return trip effect, which documents subjectively longer outbound journeys
      relative to identical inbound journeys, to inform this question. Through this
      lens, the focal event (that which will transpire at the destination) can be
      decoupled from the focal duration (the span of time between the present moment
      and arrival at that destination). Four studies document a consistent effect in
      which ambiguity awaiting at a future event (occurring at the destination) expands
      the subjective magnitude of present durations (the travel time to the
      destination). Duration judgments thus appear sensitive to an increasingly broad
      scope of factors, informing models of temporal cognition. (PsycINFO Database
      Record

PMID- 27709970
TI  - Social support and coparenting among lesbian, gay, and heterosexual adoptive
      parents.
AB  - In this study, we examined associations between qualities of families' social
      contexts and experiences of coparenting. In a sample of 92 adoptive families, we
      assessed perceived social support among 23 lesbian, 28 gay, and 41 heterosexual
      adoptive parent families and its association with parents' perceptions of their
      coparenting alliances. Results showed that parents in same- and other-sex couples
      reported receiving similar amounts of social support from family, friends, and
      significant others. Perceived social support was positively associated with
      stronger coparenting alliance among all family types. Perceived support from
      family members explained more variance in parenting alliance than did support
      from friends or significant others. These findings add to knowledge about
      fundamental family processes and enhance understanding of parenthood among
      lesbian and gay adoptive couples. (PsycINFO Database Record

PMID- 27709971
TI  - An exploratory analysis of the impact of specific interventions: Some clients
      reveal more than others.
AB  - Recent work has highlighted that process-outcome relationships are likely to vary
      depending on the client, yet there is little direct evidence regarding specific
      intervention effects in individual clients. This study attempted to address the
      hypothesis that some clients reveal more than others regarding the impact of
      specific interventions. Intensive case study analyses were applied to 2 clients
      with principal major depressive disorder and comorbid anxiety disorders receiving
      transdiagnostic psychotherapy. Clients completed a battery of symptom and
      psychological assessments of mindfulness, cognitive reappraisal use, and emotion
      avoidance on many occasions throughout treatment. Time series analyses were
      applied to symptom and change construct data. Results included: (a) significant
      decreases in depression, anxiety, and emotion avoidance from baseline to
      posttreatment were observed, as well as significant increases in mindfulness and
      reappraisal; and (b) in one case, intervention strategies exerted little
      influence on changes in key variables; in the other, emotion exposure strategies
      had the strongest influence on increases in mindfulness and present-focused
      awareness strategies had the strongest influence on reductions in emotion
      avoidance. Even when different clients appear to similarly benefit from the same
      treatment, specific intervention effects on putative change factors may be more
      prevalent for some clients and less prevalent for others. Regular assessment is
      needed to determine if a client requires an alternative set of specific
      intervention strategies. (PsycINFO Database Record

PMID- 27709972
TI  - "Distant but relative: Similarities and differences in gender role beliefs among
      African American and Vietnamese American women": Correction to Abrams et al.
      (2016).
AB  - : Reports an error in "Distant but relative: Similarities and differences in
      gender role beliefs among African American and Vietnamese American women" by
      Jasmine A. Abrams, Sarah J. Javier, Morgan L. Maxwell, Faye Z. Belgrave and Anh
      Bao Nguyen (Cultural Diversity and Ethnic Minority Psychology, 2016[Apr], Vol
      22[2], 256-267). In the article, the name of author Anh Bao Nguyen was misspelled
      as Boa Anh Nguyen. The online version of this article has been corrected. (The
      following abstract of the original article appeared in record 2015-18954-001.)
      Objectives: Research attempting to identify similarities or disentangle
      differences in ethnic minority gender role beliefs has been largely absent in the
      literature, and a gap remains for qualitative examinations of such phenomena. The
      purpose of this study is to fill this gap in the literature by providing a
      qualitative examination of the differences and similarities of gender role
      beliefs among African American and Vietnamese American women. METHODS: Thematic
      analyses were conducted with data gathered from 8 focus groups with 44 African
      American women (mean age = 44 years) and 4 focus Groups 47 Vietnamese American
      women (mean age = 42 years). Women were diverse in generational, religious, and
      educational backgrounds. RESULTS: Two similar primary themes emerged: (a) women's
      roles as chief caretakers and (b) women's responsibility to fulfill multiple
      roles. There were also similar experiences of a need to convey strength and be
      self-sacrificial. Two distinct differences that emerged from the focus groups
      were beliefs about interpersonal interactions and perceptions of societal
      expectations. CONCLUSIONS: This study demonstrates that the conceptualization of
      gender role beliefs, although at times similar, diverges among culturally
      different groups. To account for these and other culturally nuanced differences,
      measures of gender role beliefs should be culturally tailored and culturally
      specific. However, researchers have largely excluded ethnic minority women in the
      development of the most widely used measures of gender role beliefs in the U.S.
      The inclusion of diverse women in research will help prevent pitfalls of
      conflating and ignoring intragroup differences among different groups of
      marginalized women.

PMID- 27709973
TI  - Lay beliefs about emotional problems and attitudes toward mental health care
      among parents and adolescents: Exploring the impact of immigration.
AB  - OBJECTIVE: Individuals' lay beliefs about mental health problems and attitudes
      toward mental health care are thought to be influenced by the cultural background
      of these individuals. In the current study, we investigated differences between
      immigrant Dutch and native Dutch parents and adolescents in lay beliefs about
      emotional problems and attitudes toward mental health care. Additionally, among
      immigrant Dutch parents, we examined the associations between acculturation
      orientations and lay beliefs about emotional problems as well as attitudes toward
      mental health care. METHOD: In total, 349 pairs of parents and their adolescent
      children participated in our study (95 native Dutch, 85 Surinamese-Dutch, 87
      Turkish-Dutch, 82 Moroccan-Dutch). A vignette was used to examine participants'
      lay beliefs. RESULTS: Immigrant Dutch and native Dutch parents differed in their
      lay beliefs and attitudes toward mental health care, whereas hardly any
      differences were revealed among their children. Turkish-Dutch and Moroccan-Dutch
      parents showed more passive and fewer active solutions to emotional problems
      compared to native Dutch parents. Additionally, Moroccan-Dutch and Surinamese
      Dutch parents reported greater fear of mental health care compared to native
      Dutch parents. Furthermore, the results showed that immigrant Dutch parents who
      were more strongly oriented toward the Dutch culture reported less fear of mental
      health care. CONCLUSION: Our results showed clear differences in lay beliefs and
      attitudes toward mental health care between immigrant Dutch and native Dutch
      parents but not between their children. Substantial differences were also found
      between parents from different immigrant Dutch populations as well as within the
      population of immigrant Dutch parents. (PsycINFO Database Record

PMID- 27709974
TI  - Maximum likelihood versus multiple imputation for missing data in small
      longitudinal samples with nonnormality.
AB  - The study examined the performance of maximum likelihood (ML) and multiple
      imputation (MI) procedures for missing data in longitudinal research when fitting
      latent growth models. A Monte Carlo simulation study was conducted with
      conditions of small sample size, intermittent missing data, and nonnormality. The
      results indicated that ML tended to display slightly smaller degrees of bias than
      MI across missing completely at random (MCAR) and missing at random (MAR)
      conditions. Although specification of prior information in the MI imputation
      posterior (I-P) phase influenced the performance of MI, especially with nonnormal
      small samples and missing not at random (MNAR), the impact of this tight
      specification was not dramatic. Several corrected ML test statistics showed
      proper rejections rates across research designs, whereas posterior predictive p
      values for MI methods were more likely to be influenced by distribution shape and
      yielded higher rejection rates in MCAR and MAR than in MNAR. In conclusion, ML
      appears to be preferable to MI in research conditions with small missing samples
      and multivariate nonnormality whether or not strong prior information for the I-P
      phase of MI analysis is available. (PsycINFO Database Record

PMID- 27709975
TI  - Postdeviance distraction in younger and older adults: Neuro-behavioral evidence
      from speech perception.
AB  - Older adults are usually more easily distracted by task-irrelevant stimuli than
      younger ones. In addition, there is evidence that it takes them more time to
      overcome a distracting event. Here, the distracting effect of irregular switches
      in speaker location was studied in 22 younger and 22 older adults in a speech
      perception task. The participants responded to target words that were presented
      either from a frequent location (standard trials) or a rare location (deviant
      trials). Behavioral performance measures, event-related brain potentials (ERPs),
      and EEG synchronization (intertrial coherence [ITC]) were analyzed. Behavioral
      performance was not only decreased in deviant trials, but also in subsequent
      standard trials, indicating an effect of so-called postdeviance distraction. The
      negative impact of the distracting event (i.e., the switch in speaker location)
      on the processing of subsequent (standard) trials was more pronounced in the
      older versus younger group. The EEG analyses revealed a decreased N2 amplitude
      and increased latencies in P2 and P3a in the older group, suggesting a reduced
      and delayed attentional control. Moreover, there were age-related changes in late
      (200-450 ms) theta ITCs: While the ITC of the young remained constant in trials
      following a deviant, the ITC of the old decreased, suggesting a decline in
      processing of stimuli following (task-irrelevant) switches in speaker location.
      This could contribute to age-related deficits in speech comprehension in
      spatially variable listening situations. (PsycINFO Database Record

PMID- 27709976
TI  - Boredom begs to differ: Differentiation from other negative emotions.
AB  - Boredom research is booming. Nonetheless, a comprehensive understanding of
      boredom in relation to other negative emotions is lacking. This ambiguity impedes
      accurate interpretation of boredom's causes and consequences. To gain more
      insights into boredom, we examined in detail how it differs from a range of other
      negative experiences, namely sadness, anger, frustration, fear, disgust,
      depression, guilt, shame, regret, and disappointment. Our research indicates that
      the appraisals associated with boredom distinguish it clearly from other negative
      emotions; conceptually (Study 1), in terms of state experiences (Study 2), and in
      terms of individual differences in these experiences (Study 3). Our findings
      suggest that boredom is mild in negative valence, low in arousal, is associated
      with low perceived challenge and low perceived meaningfulness, and has low
      relevance to moral judgment and behavior. Boredom also involves low attention
      given to situations and tasks, and the lack of perceived meaningfulness and
      attention associated with boredom emerged as particularly distinctive
      characteristics. The findings underscore the importance of carefully
      discriminating boredom from other emotions in experimental induction,
      psychometric assessment, and conceptual discussion. (PsycINFO Database Record

PMID- 27709977
TI  - On the relationship between positive and negative affect: Their correlation and
      their co-occurrence.
AB  - Understanding the nature of emotional experience requires understanding the
      relationship between positive and negative affect. Two particularly important
      aspects of that relationship are the extent to which positive and negative affect
      are correlated with one another and the extent to which they co-occur. Some
      researchers have assumed that weak negative correlations imply greater co
      occurrence (i.e., more mixed emotions) than do strong negative correlations, but
      others have noted that correlations may imply very little about co-occurrence. We
      investigated the relationship between the correlation between positive and
      negative affect and co-occurrence. Participants in each of 2 samples provided
      moment-to-moment happiness and sadness ratings as they watched an evocative film
      and listened to music. Results indicated (a) that 4 measures of the correlation
      between positive and negative affect were quite highly related to 1 another; (b)
      that the strength of the correlation between measures of mixed emotions varied
      considerably; (c) that correlational measures were generally (but not always)
      weakly correlated with mixed emotion measures; and (d) that bittersweet stimuli
      consistently led to elevations in mixed emotion measures but did not consistently
      weaken the correlation between positive and negative affect. Results highlight
      that the correlation between positive and negative affect and their co-occurrence
      are distinct aspects of the relationship between positive and negative affect.
      Such insight helps clarify the implications of existing work on age-related and
      cultural differences in emotional experience and sets the stage for greater
      understanding of the experience of mixed emotions. (PsycINFO Database Record

PMID- 27709978
TI  - An Internet-based virtual reality intervention for enhancing self-esteem in women
      with disabilities: Results of a feasibility study.
AB  - PURPOSE: To examine the feasibility of an online self-esteem enhancement group
      program for women with disabilities. METHOD: A sample of 19 racially and
      ethnically diverse, community-living women with physical disabilities, 22 to 61
      years old, participated in a 7-session interactive group intervention (extending
      Hughes et al., 2004) in the 3-D, immersive, virtual environment of
      SecondLife.com, using avatars with voice and text communication. Baseline and
      postintervention questionnaires were administered online. Criteria for
      determining feasibility were (a) enrollment, (b) engagement, (c) acceptability,
      and (d) improvement on measures of self-esteem, depression, self-efficacy, and
      social support. RESULTS: We attained our enrollment goal and engagement exceeded
      expectations. Acceptability was positive; participants gave "helpful" and
      "enjoyable" ratings of 3.21 and 3.27, respectively, (mean on a 1 to 4 Likert
      scale, where 4 = high) to 5 intervention components-session materials, group
      sharing and discussion, relaxation exercises, action planning, and group
      excursions. Significant increases from baseline to postintervention were found on
      the Rosenberg Self-Esteem Scale (p = .02; Cohen's d = .60) and the Center for
      Epidemiologic Studies Depression Scale-10 (p = .005; Cohen's d = .74), with a
      trend toward significance on the Generalized Self-Efficacy Scale (p = .08;
      Cohen's d = .42). The intervention did not significantly affect the measure of
      social support. IMPLICATIONS: An intervention to enhance self-esteem may have a
      corollary benefit on depressive symptomatology. Offering psycho-educational,
      small group interventions using online virtual worlds shows promise for
      circumventing disability-related and environmental barriers to accessing mental
      health services experienced by women with mobility limitations, and should
      undergo further development and testing. (PsycINFO Database Record

PMID- 27709979
TI  - Risk factors that predict future onset of each DSM-5 eating disorder: Predictive
      specificity in high-risk adolescent females.
AB  - Because no single report has examined risk factors that predict future onset each
      type of eating disorder and core symptom dimensions that crosscut disorders, we
      addressed these aims to advance knowledge regarding risk factor specificity. Data
      from 3 prevention trials that targeted young women with body dissatisfaction (N =
      1,272; Mage = 18.5, SD = 4.2) and collected annual diagnostic interview data over
      3-year follow-up were combined to identify predictors of subthreshold/threshold
      anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and
      purging disorder (PD). Negative affect and functional impairment predicted onset
      of all eating disorders. Thin-ideal internalization, body dissatisfaction,
      dieting, overeating, and mental health care predicted onset of
      subthreshold/threshold BN, BED, and PD; positive thinness expectations, denial of
      cost of pursuing the thin ideal, and fasting predicted onset of 2 of these 3
      disorders. Similar risk factors predicted core eating disorder symptom onset. Low
      BMI and dieting specifically predicted onset of subthreshold/threshold AN or low
      BMI. Only a subset of factors showed unique predictive effects in multivariate
      models, likely due to moderate correlations between the risk factors (M r = .14).
      Results provide support for the theory that pursuit of the thin ideal and the
      resulting body dissatisfaction, dieting, and unhealthy weight control behaviors
      increase risk for binge/purge spectrum eating disorders, but suggest that youth
      who are inherently lean, rather than purposely pursuing the thin ideal, are at
      risk for AN. Impaired interpersonal functioning and negative affect are
      transdiagnostic risk factors, suggesting these factors should be targeted in
      prevention programs. (PsycINFO Database Record

PMID- 27709981
TI  - Deontological coherence: A framework for commonsense moral reasoning.
AB  - We review a broad range of work, primarily in cognitive and social psychology,
      that provides insight into the processes of moral judgment. In particular, we
      consider research on pragmatic reasoning about regulations and on coherence in
      decision making, both areas in which psychological theories have been guided by
      work in legal philosophy. Armed with these essential prerequisites, we sketch a
      psychological framework for how ordinary people make judgments about moral
      issues. Based on a literature review, we show how the framework of deontological
      coherence unifies findings in moral psychology that have often been explained in
      terms of a grab-bag of heuristics and biases. (PsycINFO Database Record

PMID- 27709980
TI  - Hyperfocusing of attention on goal-related information in schizophrenia: Evidence
      from electrophysiology.
AB  - Schizophrenia clearly involves impairments of attention, but the precise nature
      of these impairments has been difficult to determine. One possibility is that the
      deficit in attention is a secondary consequence of a deficit in goal maintenance.
      However, recent research suggests that people with schizophrenia (PSZ) actually
      focus attention more strongly on objects containing goal-relevant features. To
      test these competing hypotheses, we recorded event-related potentials (ERPs) from
      PSZ (N = 20) and healthy control subjects (HCS; N = 20) while they looked for a
      particular target color at fixation and tried to ignore lateral distractors that
      sometimes matched the target color (target-color distractors). Goal maintenance
      was made trivially easy by the continual presentation of a goal reminder. We
      found that HCS were able to successfully suppress target-color distractors
      (leading to a distractor positivity ERP component), whereas PSZ focused attention
      on these items (leading to an N2-posterior-contralateral ERP component). This
      suggests that, when maintaining a task set, PSZ engage in aberrant focusing of
      attention, or hyperfocusing, on goal-relevant features. (PsycINFO Database Record

PMID- 27709983
TI  - More than just beliefs: Experience and beliefs jointly contribute to volume
      effects on metacognitive judgments.
AB  - Experience-based cues, such as perceptual fluency, have long been thought to
      influence metacognitive judgments (Kelley & Jacoby, 1996; Koriat, 1997). Studies
      found that manipulations of perceptual fluency via changes in font and volume
      alter Judgments of Learning (JOLs) without influencing memory performance (Rhodes
      & Castel, 2008, 2009). Nonetheless, recent research (Mueller, Tauber, & Dunlosky,
      2013; Mueller, Dunlosky, Tauber, & Rhodes, 2014, 2016) has challenged the notion
      that experience-based cues such as fluency are the primary basis for item-level
      JOLs, arguing instead that preexisting beliefs about these manipulations are
      responsible for these effects. For the first time, we compared global
      metacognitive judgments to item-level JOLs made during study to independently
      assess the contribution of beliefs and experience to volume-effects on JOLs. In 3
      experiments, we found evidence for strong beliefs about volume-effects on memory,
      both before and after a study-test phase. However, these beliefs either did not
      account for the volume effect on JOLs (Experiment 3) or only partially accounted
      for the volume effect on JOLs (Experiments 1 and 2). Further, in Experiments 2
      and 3 global performance estimates (before and after study) did not differ with
      respect to the volume dose whereas item-level JOLs generally varied with dose
      strength. Taken together, our findings suggest that both beliefs and experience
      based cues contribute independently to the effects of volume on item-level JOLs,
      but that beliefs alone cannot fully account for the effects of volume on item
      level JOLs. (PsycINFO Database Record

PMID- 27709982
TI  - Drawing the line between constituent structure and coherence relations in visual
      narratives.
AB  - Theories of visual narrative understanding have often focused on the changes in
      meaning across a sequence, like shifts in characters, spatial location, and
      causation, as cues for breaks in the structure of a discourse. In contrast, the
      theory of visual narrative grammar posits that hierarchic "grammatical"
      structures operate at the discourse level using categorical roles for images,
      which may or may not co-occur with shifts in coherence. We therefore examined the
      relationship between narrative structure and coherence shifts in the segmentation
      of visual narrative sequences using a "segmentation task" where participants drew
      lines between images in order to divide them into subepisodes. We used
      regressions to analyze the influence of the expected constituent structure
      boundary, narrative categories, and semantic coherence relationships on the
      segmentation of visual narrative sequences. Narrative categories were a stronger
      predictor of segmentation than linear coherence relationships between panels,
      though both influenced participants' divisions. Altogether, these results support
      the theory that meaningful sequential images use a narrative grammar that extends
      above and beyond linear semantic shifts between discourse units. (PsycINFO
      Database Record

PMID- 27709984
TI  - Adaptation and fallibility in experts' judgments of novice performers.
AB  - Competition judges are often selected for their expertise, under the belief that
      a high level of performance expertise should enable accurate judgments of the
      competitors. Contrary to this assumption, we find evidence that expertise can
      reduce judgment accuracy. Adaptation level theory proposes that discriminatory
      capacity decreases with greater distance from one's adaptation level. Because
      experts' learning has produced an adaptation level close to ideal performance
      standards, they may be less able to discriminate among lower-level competitors.
      As a result, expertise increases judgment accuracy of high-level competitions but
      decreases judgment accuracy of low-level competitions. Additionally, we
      demonstrate that, consistent with an adaptation level theory account of expert
      judgment, experts systematically give more critical ratings than intermediates or
      novices. In summary, this work demonstrates a systematic change in human
      perception that occurs as task learning increases. (PsycINFO Database Record

PMID- 27709985
TI  - Isolating component processes of posterror slowing with the psychological
      refractory period paradigm.
AB  - Posterror slowing (PES) refers to an increased response time following errors.
      While PES has traditionally been attributed to control adjustments, recent
      evidence suggested that PES reflects interference. The present study investigated
      the hypothesis that control and interference represent 2 components of PES that
      differ with respect to their time course and task-specificity. To this end, we
      investigated PES in a dual-task paradigm in which participants had to classify
      colors and tones that were separated by a variable stimulus onset asynchrony
      (SOA). Errors in the color task caused PES both in the tone task of the same
      trial and the color task of the subsequent trial. However, while the former
      effect disappeared with an increasing SOA, the latter effect was independent of
      SOA and lasted for several trials. This suggests that errors simultaneously
      induce task-unspecific, transient PES reflecting interference and task-specific,
      more long-lasting PES reflecting control adjustments. (PsycINFO Database Record

PMID- 27709986
TI  - Estradiol is associated with altered cognitive and physiological responses during
      fear conditioning and extinction in healthy and spider phobic women.
AB  - The first-line psychological treatment for anxiety disorders is exposure therapy,
      which can be modeled in the laboratory using fear extinction. In healthy women,
      estradiol levels predict return of fear following extinction, whereas low levels
      are associated with greater return of fear. Investigating whether estradiol is
      similarly associated with extinction in clinically anxious women may provide
      insight to mechanisms underlying symptom relapse following exposure therapy. In
      the present study, women with spider phobia and healthy women participated in a 2
      day fear conditioning and extinction procedure during a period of high or low
      estradiol levels. Skin conductance responses, shock expectancy, and valence
      ratings were measured throughout. Women exhibited comparable decreases in
      physiological arousal from conditioning to the end of extinction training on Day
      1. However, compared to women with high estradiol, and irrespective of clinical
      status, women with low estradiol exhibited significant return of physiological
      arousal at extinction recall on Day 2, despite accurate ratings regarding the
      likelihood of shock. Low estradiol women also reported heightened threat
      expectancy and physiological responding during presentation of safety cues. These
      results may point to novel means of enhancing exposure therapy in women by timing
      treatment delivery during periods of higher estradiol levels. (PsycINFO Database
      Record

PMID- 27709987
TI  - PDTRT special section: Current trends in borderline personality disorder
      research.
AB  - One of the enjoyable benefits of being an editor of a journal is the ability to
      develop special sections. It is evident simply from a perusal of a typical issue
      of Personality Disorders: Theory, Research, and Treatment (PDTRT) that a common
      focus of research is borderline personality disorder (BPD). BPD is among, if not
      the, most heavily researched personality disorder. It is only natural to have the
      first special section within my tenure as editor concern this personality
      disorder. Provided within this special section are review papers of current
      trends in BPD research by young (at least compared to me), leading, and
      innovative BPD researchers. (PsycINFO Database Record

PMID- 27709989
TI  - Borderline personality disorder and the emerging field of developmental
      neuroscience.
AB  - Over the past 2 decades there has been a dramatic shift in understanding of
      personality disorders, such as borderline personality disorder (BPD). What was
      historically viewed as an entrenched pattern of antagonistic, interpersonally
      dependent, and uncorrectable conduct is now seen as the outcome of complex-yet
      modifiable-developmental processes. The borderline label, which once inspired
      such harsh opprobrium in clinical communities that early diagnosis was considered
      taboo, is now increasingly applied to adolescents who are receiving effective
      treatment and desisting from a borderline trajectory. Research examining the
      developmental origins and early manifestations of BPD is increasing rapidly,
      making it an appropriate time to take stock of current developmental research and
      articulate an agenda for the future. We identify 4 challenges that continue to
      impede innovative research on borderline personality development: (a) inadequate
      attention to continuity and discontinuity across development, (b) medical and
      diagnostic systems that localize personality pathology within the individual, (c)
      the lingering belief that biological research is antithetical to
      contextual/interpersonal understandings of psychopathology (and vice versa), and
      (d) reluctance to reach across disciplinary and developmental boundaries to
      identify creative paradigms and foster innovative discovery. In order to overcome
      these challenges, we propose an approach to future research on adolescent
      borderline pathology that integrates developmental psychopathology, social and
      affective neuroscience, and personality theory perspectives. This intersection
      the developmental neuroscience of personality pathology-offers theoretical and
      methodological advantages over disciplinary isolation and is fertile ground for
      generating novel hypotheses on the development and prevention of BPD. (PsycINFO
      Database Record

PMID- 27709988
TI  - A systematic review of risk factors prospectively associated with borderline
      personality disorder: Taking stock and moving forward.
AB  - There is an urgent need to identify signs that harbinger onset of borderline
      personality disorder (BPD). Advancement in this area is required to refine
      developmental theories, discover etiological mechanisms, improve early detection,
      and achieve our ultimate goal of prevention. Though many studies have supported a
      wide range of factors that increase subsequent risk for BPD, this literature has
      yet to be critically evaluated, and there are no comprehensive reviews that
      examine and integrate these findings. To address this limitation, we conducted a
      systematic review to summarize and synthesize the current literature. Electronic
      databases were systematically searched for prospective, longitudinal studies that
      examined risk factors of subsequent BPD outcomes (features, symptoms, diagnosis),
      resulting in a total of 39 studies, reflecting 24 unique samples. Though
      increased risk for BPD was reliably attributed to multiple factors within social,
      family, maltreatment, and child domains, the most striking limitation of this
      research is its lack of disorder-specific findings. Additional limitations,
      including notable heterogeneity in sampling methodology, symptom assessment
      methodology, and developmental timing of assessments, are discussed in terms of
      how close we are to pinpointing who is most at risk and why in an attempt to
      provide a roadmap for future research. (PsycINFO Database Record

PMID- 27709990
TI  - Current trends in BPD research as indicative of a broader sea-change in
      psychiatric nosology.
AB  - The aim of the Special Section that this paper contributes to is to review
      current trends in borderline personality disorder (BPD) research. Three major
      trends were identified. First, there has been a marked increase in studies that
      attempt to locate BPD in the dimensional latent structure of psychopathology.
      Second, identifying the endophenotypic markers associated with BPD has become a
      focus of interest. Here, we focus on one endophenotype in the form of impaired
      self-other processing. Third, there has been an explosion of research into the
      developmental aspects of BPD specifically focused on uncovering complex Biology *
      Environment interactions in the development of BPD. This paper discusses how
      these trends (Dimensions, Biology, and Development) are challenging the nature
      and form of BPD as we know it, and may be indicative of a broader sea-change in
      psychiatric nosology. (PsycINFO Database Record

PMID- 27709991
TI  - The role of emotion dysregulation in the presence, associated difficulties, and
      treatment of borderline personality disorder.
AB  - Theory and research identify emotion dysregulation as one of the primary
      mechanisms underlying borderline personality disorder (BPD) and related
      pathology. Yet, despite the extensive research documenting an association between
      emotion dysregulation and BPD, many questions regarding the precise role of
      emotion dysregulation in the development and treatment of BPD and its associated
      difficulties remain unanswered. This paper reviews the extant literature on the
      role of emotion dysregulation in BPD and its associated difficulties, as well as
      the treatment of BPD-related pathology, and identifies important next steps for
      future research in this area. In particular, this review highlights the need for
      further research examining: (a) the dimensions of emotion dysregulation that are
      unique to BPD, (b) the role and nature of interpersonal (vs. intrapersonal)
      emotion regulation in BPD, (c) the role of emotion dysregulation in the physical
      (vs. mental) health problems associated with BPD, and (d) the role of emotion
      regulation in efficacious treatments for BPD. Such research has the potential to
      elucidate the precise emotion regulation deficits that are most relevant (and
      central) to BPD, the active ingredients and mechanisms of change in current
      efficacious treatments for BPD, and the most effective and efficient targets for
      integrative treatments for this population. (PsycINFO Database Record

PMID- 27709992
TI  - Leadership emergence over time in short-lived groups: Integrating expectations
      states theory with temporal person-perception and self-serving bias.
AB  - Research into leadership emergence typically focuses on the attributes of the
      emergent leader. By considering also the attributes of perceivers and the passage
      of time, we develop a more complete theory of leadership emergence in short-lived
      groups. Using expectation states theory as an overarching theoretical framework,
      and integrating it with the surface- and deep-level diversity literature and with
      theories of self-serving biases, we examine the predictors of leadership
      emergence in short timeframes. We conduct a field study in a military assessment
      boot camp (a pilot study, n = 60; and a main study, n = 89). We use cross
      sectional and longitudinal exponential random graph models to analyze data on
      participants' abilities and on their perceptions of who, in their respective
      groups, were "leaders." We find that the criteria by which people perceive
      leadership in others change over time, from easily noticeable attributes to
      covert leadership-relevant attributes, and that people also rely on leadership
      relevant attributes that they possess at high levels to inform their perceptions
      of leadership in others. The integration of expectation states theory, attribute
      salience over time and theories of self-serving bias is needed for a full
      understanding of leadership emergence in groups, because perceivers' own
      abilities are instrumental in shaping their perceptions of emergent leadership
      over time. Theoretical and practical implications are discussed. (PsycINFO
      Database Record

PMID- 27709993
TI  - Binding an event to its source at encoding improves children's source monitoring.
AB  - Children learn information from a variety of sources and often remember the
      content but forget the source. Whereas the majority of research has focused on
      retrieval mechanisms for such difficulties, the present investigation examines
      whether the way in which sources are encoded influences future source monitoring.
      In Study 1, 86 children aged 3 to 8 years participated in 2 photography sessions
      on different days. Children were randomly assigned to either the Difference
      condition (they were asked to pay attention to differences between the 2 events),
      the Memory control condition (asked to pay attention with no reference to
      differences), or the No-Instruction control (no special instructions were given).
      One week later, during a structured interview about the photography session, the
      3- to 4-year-olds in the No-Instruction condition were less accurate and
      responded more often with 'do not know' than the 7- to 8-year-olds. However, the
      older children in the Difference condition made more source confusions than the
      younger children suggesting improved memory for content but not source. In Study
      2, the Difference condition was replaced by a Difference-Tag condition where
      details were pointed out along with their source (i.e., tagging source to
      content). Ninety-four children aged 3 to 8 years participated. Children in the
      Difference-Tag condition made fewer source-monitoring errors than children in the
      Control condition. The results of these 2 studies together suggest that binding
      processes at encoding can lead to better source discrimination of experienced
      events at retrieval and may underlie the rapid development of source monitoring
      in this age range. (PsycINFO Database Record

PMID- 27709994
TI  - IQ at age 12 following a history of institutional care: Findings from the
      Bucharest Early Intervention Project.
AB  - Young children removed from institutions and placed into foster care or adoptive
      homes have been shown to experience significant gains in IQ relative to children
      who remain in institutions. Less is known about the long-term impact of severe
      early deprivation on development in late childhood. Data are presented from a
      follow-up of children at 12 years of age in the Bucharest Early Intervention
      Project, a randomized clinical trial of foster care for institutionally reared
      children. Of the original 136 children in the study, 107 were tested with the
      Wechsler Intelligence Scale for Children-IV. Results revealed continued benefit
      from the intervention through age 12, with 12-year-old children placed in foster
      care scoring significantly higher on full-scale IQ compared to their peers who
      received prolonged institutional care. Longitudinal IQ data revealed 2 IQ
      profiles from early to late childhood. Attachment security emerged as a
      significant predictor of a profile of stable, typical IQ scores over time. We
      demonstrate the continued importance of foster care intervention and the negative
      effects of severe, early psychosocial deprivation on IQ into late childhood.
      (PsycINFO Database Record

PMID- 27709995
TI  - Time-varying effects of family ethnic socialization on ethnic-racial identity
      development among Latino adolescents.
AB  - Previous research has established that family ethnic socialization messages
      promote ethnic-racial identity (ERI) development, yet it is unknown whether these
      effects remain constant throughout adolescence. The current study examined the
      time-varying effects of family ethnic socialization on ERI exploration and
      resolution among Latino adolescents (n = 323, Mage at T1 = 15.31, SDage = .76;
      49.5% female). As adolescents progressed from middle to late adolescence, the
      relation between family ethnic socialization and exploration became stronger,
      while the relation between family ethnic socialization and resolution became
      weaker, with a significant difference between the magnitude of these associations
      emerging in late adolescence. The findings underscore the differential impact
      that family ethnic socialization messages can have on ERI developmental processes
      at different points in adolescence. In addition, the current study provides a
      useful illustration of how time-varying effects modeling can be used to examine
      how familial influences on youth development can change across developmental
      periods. (PsycINFO Database Record

PMID- 27709997
TI  - Maternal mind-mindedness and children's school readiness: A longitudinal study of
      developmental processes.
AB  - This study aimed to test a 5-wave sequential mediation model linking maternal
      mind-mindedness during infancy to children's school readiness in kindergarten
      through a serial mediation involving child language and effortful control in
      toddlerhood and the preschool years. Among a sample of 204 mother-child dyads, we
      assessed maternal mind-mindedness when children were aged 1 year, child
      expressive vocabulary at age 2, effortful control at ages 3 and 4, and finally
      cognitive school readiness in kindergarten. The results corroborated the model,
      suggesting that the prospective association between early mind-mindedness and
      later cognitive school readiness was entirely mediated by the proposed sequence
      of mediators, all of which were necessary to account for this longitudinal
      association. These findings suggest that the potential of parental mind
      mindedness to support children's cognitive development may have been
      underestimated, and that its putative positive influence may take the form of a
      developmental cascade unfolding during the preschool years and entailing the
      acquisition of basic skills that serve as building blocks for further learning
      and development. (PsycINFO Database Record

PMID- 27709996
TI  - The risks and rewards of sexual debut.
AB  - The sex-positive framework of sexual development hypothesizes that healthy sexual
      experiences can be developmentally appropriate and rewarding for adolescents
      despite the risks involved. Research has not examined whether risky behaviors and
      rewarding cognitions actually change with sexual debut at a normative or late
      age. This study measured the longitudinal impact of sexual debut using 7 waves of
      data from 88 male and 86 female adolescents from a western U.S. city who were in
      the 10th grade at the study's onset. We used piecewise growth curve analyses to
      compare behaviors and cognitions before and after first sexual intercourse for
      those whose debut was at a normative or late age. These analyses revealed that
      sexual debut was related to rewards, including increases in romantic appeal and
      sexual satisfaction. In addition, internalizing symptoms declined over time after
      sexual debut, and substance use grew at a slower rate after sexual debut. We also
      examined whether differences existed among those whose debut was at an early,
      normative, or late age. Linear growth curve analyses revealed early sexual debut
      was related to risks, such as greater substance use, more internalizing and
      externalizing symptoms, and lower global self-worth. Rewards associated with an
      early debut included greater romantic appeal, dating satisfaction (males only),
      and sexual satisfaction (males only). Although there are some inherent risks with
      sexual activity, the results suggest that sexual debut at a normative or late age
      is also associated with a decrease in some risks and an increase in rewards.
      (PsycINFO Database Record

PMID- 27709998
TI  - The developmental course of supportive dyadic coping in couples.
AB  - Drawing from a relational developmental systems (RDS) perspective (Lerner, Agans,
      DeSouza, & Gasca, 2013) and data from 1,427 continuously partnered young adult
      and midlife mixed-sex couples over the first 5 years of the German Panel Analysis
      of Intimate Relationships and Family Dynamics (pairfam), this study examined the
      developmental course of supportive dyadic coping, or the frequency with which one
      provides practical and emotional support when his or her partner encounters
      stress. Latent change score (LCS) modeling results revealed that supportive
      dyadic coping gradually declined for both male and female partners, but there was
      significant diversity underlying these trajectories. Higher levels of supportive
      dyadic coping were associated with a more gradual decline in support provided by
      a partner. Among young adults, a more rapid decline in male partner supportive
      dyadic coping predicted a slower rate of decline in support from female partners.
      Finally, we considered possible bidirectional relations between contextual
      stressors and supportive dyadic coping trajectories. Providing higher levels of
      support predicted a more gradual decline in self-rated health for male partners.
      Having more children and experiencing economic pressure predicted steeper
      declines in supportive dyadic coping over time for both male and female partners.
      (PsycINFO Database Record

PMID- 27710000
TI  - "Because if you don't put the top on, it will spill": A longitudinal study of
      sibling teaching in early childhood.
AB  - Naturalistic dyadic sequences of teaching and learning involving older and
      younger siblings were investigated in 39 middle-class dyads over a 2-year period
      in early childhood. Siblings were observed during ongoing interactions in the
      home setting for 6 90-min sessions at both Time 1 (older sibling M age = 4.4
      years; younger sibling M age = 2.4 years) and Time 2 (older sibling M age = 6.3
      years; younger sibling M age = 4.4 years). Sequences of sibling-directed teaching
      (T1 n = 353; T2 n = 1,039) were identified from the observation transcripts and
      coded for teacher/learner roles, initiation of teaching, teaching strategies, and
      learner response. Older siblings were more likely to engage in teaching at both
      time points, but the proportion of younger sibling teaching increased
      significantly from T1 to T2, partially because older siblings requested teaching
      more often from their younger siblings at T2. Siblings' use of teaching
      strategies varied across time points, while both older and younger sibling
      learners generally accepted or complied with the teaching. A final set of
      analyses examined birth-order effects while controlling for age by comparing
      older sibling teachers at age 4 (T1) to younger sibling teachers at age 4 (T2).
      At T1 first-born older siblings (age 4) engaged in a wider range and more
      sophisticated teaching strategies than second-born younger siblings (age 4) at
      T2. Findings highlight the bidirectional nature of teacher-learner interactions
      and are discussed in light of recent theory and research indicating that the
      sibling relationship is a rich context for children's learning and development.
      (PsycINFO Database Record

PMID- 27709999
TI  - The development of self-regulation across early childhood.
AB  - The development of early childhood self-regulation is often considered an early
      life marker for later life successes. Yet little longitudinal research has
      evaluated whether there are different trajectories of self-regulation development
      across children. This study investigates the development of behavioral self
      regulation between the ages of 3 and 7 years, with a direct focus on possible
      heterogeneity in the developmental trajectories, and a set of potential
      indicators that distinguish unique behavioral self-regulation trajectories.
      Across 3 diverse samples, 1,386 children were assessed on behavioral self
      regulation from preschool through first grade. Results indicated that majority of
      children develop self-regulation rapidly during early childhood, and that
      children follow 3 distinct developmental patterns of growth. These 3 trajectories
      were distinguishable based on timing of rapid gains, as well as child gender,
      early language skills, and maternal education levels. Findings highlight early
      developmental differences in how self-regulation unfolds, with implications for
      offering individualized support across children. (PsycINFO Database Record

PMID- 27710001
TI  - Trauma, posttraumatic stress disorder symptoms, and dissociative experiences
      during men's intimate partner violence perpetration.
AB  - OBJECTIVE: Research with partner-violent men has found that a subset of this
      population reports dissociative experiences during their violence (e.g.,
      inability to remember violence [despite admission that it had occurred];
      flashbacks during violence). However, the literature examining this phenomenon
      has been primarily limited to clinical observations and case studies, and there
      is a need for more thorough empirical investigation regarding the prevalence and
      correlates of dissociative violence among individuals in intimate partner
      violence (IPV) intervention programs. The primary goals of this study were to
      provide descriptive information about the rates of endorsement of dissociative
      experiences during IPV perpetration and to examine their associations with trauma
      exposure and posttraumatic stress disorder (PTSD) symptoms. METHOD: Participants
      were 302 men presenting for services at a community-based IPV intervention
      program. All variables were assessed via self-report and clinician interview at
      program intake. RESULTS: Results indicated that 22.2% of participants reported 1
      or more dissociative experiences during partner violence perpetration.
      Additionally, frequency of dissociative IPV perpetration showed significant
      positive correlations with the total number of potentially traumatic events
      (PTEs) reported and PTSD symptoms, with effect sizes in the small and medium
      ranges of magnitude, respectively. Finally, PTSD symptoms significantly mediated
      the relationship between total number of PTEs and dissociative IPV perpetration.
      CONCLUSIONS: Findings indicate a potentially meaningful relationship between
      trauma, PTSD symptoms, and dissociative experiences during IPV perpetration.
      Further qualitative and quantitative investigation is needed to better understand
      this phenomenon and how it can be addressed in IPV treatment. (PsycINFO Database
      Record

PMID- 27710002
TI  - Development of the Vicarious Resilience Scale (VRS): A measure of positive
      effects of working with trauma survivors.
AB  - OBJECTIVE: Attending to the potential impacts, both positive and negative, of
      clinical work with trauma survivors on professionals themselves is a crucial
      aspect of clinical training and supervision. Vicarious resilience refers to
      unique, positive effects that transform therapists in response to witnessing
      trauma survivors' resilience and recovery process. This study describes the
      development and exploratory factor analysis of the first instrument to assess
      vicarious resilience. METHOD: The Vicarious Resilience Scale (VRS) was developed
      and administered via electronic survey to 190 helping professionals from around
      the globe working with survivors of severe traumas, such as torture. RESULTS:
      Exploratory factor analysis yielded 7 factors: Changes in life goals and
      perspective, client-inspired hope, increased recognition of clients' spirituality
      as a therapeutic resource, increased capacity for resourcefulness, increased self
      awareness and self-care practices, increased consciousness about power and
      privilege relative to clients' social location, and increased capacity for
      remaining present while listening to trauma narratives. The Cronbach's alpha
      reliability of the VRS was .92 and, as hypothesized, the VRS was moderately and
      positively correlated with posttraumatic growth and compassion satisfaction,
      indicating convergent validity. The VRS was not significantly correlated with
      compassion fatigue (CF) or burnout, indicating discriminant validity and that
      vicarious resilience is a unique construct that is not merely "the opposite" of
      CF or burnout. CONCLUSION: The VRS possesses sound psychometric properties and
      can be utilized in supervision and training contexts and for self-assessment by
      professionals working with trauma survivors to aid the recognition and
      cultivation of vicarious resilience. (PsycINFO Database Record

PMID- 27710003
TI  - Feasibility and effectiveness of narrative exposure therapy and cognitive
      behavioral therapy in a context of ongoing violence in South Africa.
AB  - OBJECTIVE: In an observer-blinded intervention trial, we tested the reduction of
      posttraumatic stress symptoms, aggressive attitude, and behavior in young males
      living in a context of ongoing community and gang violence by means of (a)
      forensic offender rehabilitation narrative exposure therapy (FORNET), and (b) the
      cognitive-behavioral intervention "Thinking for a Change" (TFAC). A waiting list
      served as the control condition. METHOD: A total of 39 young men were included in
      the data analysis: 15 completed FORNET, 11 underwent cognitive-behavioral therapy
      (CBT), and 13 were on a waiting list for later treatment. The primary efficacy
      endpoints were the PTSD Symptom Scale-Interview (PSS-I) severity score, the
      Appetitive Aggression Scale (AAS) score, and the number of perpetrated violent
      event types 8 months (on average) after treatment. RESULTS: Only in the sample
      receiving FORNET were posttraumatic stress disorder (PTSD) scores significantly
      reduced at the first follow-up (Cohen's d = -0.97) and significantly different
      from those of the control group (Cohen's d = -1.03). The changes in scores for
      appetitive aggression and perpetrated events were not significant for any of the
      treatment conditions. CONCLUSIONS: The study shows that trauma-focused treatment
      can reduce the psychological symptoms of posttraumatic stress even for
      individuals living under unsafe conditions in low-income urban communities.
      However, achieving changes in violent behavior within a context of ongoing
      violence may require more than the treatment of trauma-related suffering,
      confrontation with one's offenses, or cognitive-behavioral interventions.
      (PsycINFO Database Record

PMID- 27710004
TI  - Complex trauma in childhood, a psychiatric diagnosis in adulthood: Making meaning
      of a double-edged phenomenon.
AB  - OBJECTIVE: No known research explores the double-edged phenomenon of childhood
      trauma/adult mental health consumer. Therefore, whether receiving a psychiatric
      diagnosis in light of childhood trauma supports or impedes psychological
      wellbeing in adult life, is unknown. METHOD: Interpretative phenomenological
      analysis (IPA) provided the methodological framework. Data were collected through
      the use of semistructured interviews. Analysis sought thematic representation
      from subjective interpretations of the experienced phenomenon: childhood trauma
      survivor/mental health consumer. RESULTS: Data revealed 1 superordinate theme,
      Childhood Betrayal, Identity, and Worthiness, that overarched 5 subordinate
      themes a) legacies, (b) the label, (c) putting the jigsaw together, (d) stigma,
      and (e) better than good enough self. Legacies of doubt that perpetuated "not
      good enough" delayed the development of an adult identity of worthiness in these
      participants. Importantly, the right diagnosis separated self as worthy-adult
      from self as traumatized child and facilitated positive change for breaking
      harmful cycles, self-valuing, and increased empathy, wisdom, and patience.
      CONCLUSIONS: Findings inform future research and therapeutic practice in regards
      to adult help seeking behaviors in light of childhood trauma, often postponed
      through fear of stigma associated with mental health diagnoses and services.
      Similarly, findings suggest that ameliorating wellbeing may be dependent on a
      therapeutic relationship in which accuracy or right fit of diagnosis provides a
      conduit for the client to disengage from self-blame, unworthiness, and "not good
      enough." (PsycINFO Database Record

PMID- 27710005
TI  - The role of substance use coping in the relation between childhood sexual abuse
      and depression among methamphetamine users in South Africa.
AB  - OBJECTIVE: Childhood sexual abuse (CSA) is a critical global health issue
      associated with poor psychosocial outcomes. Individuals with CSA histories are at
      risk for drug use, which is a growing problem in the Western Cape of South
      Africa. The present study of methamphetamine users in this region examined
      whether substance use coping, a contextually relevant type of avoidance-based
      coping, mediates the relation between CSA and depressive symptoms. METHOD:
      Participants included 161 men and 108 women seeking treatment for methamphetamine
      use. Participants completed a computer-assisted survey and a face-to-face
      interview with clinic staff to evaluate history of CSA, current substance use
      severity and coping, and current depressive symptoms. RESULTS: Nearly a third of
      participants reported a history of CSA, and the average methamphetamine use
      severity score exceeded the threshold of high risk. A history of CSA was
      significantly associated with higher substance use coping and more depression
      symptoms. Substance use coping was a significant mediator of the association
      between CSA and depression symptoms. CONCLUSIONS: In this study of high-risk
      methamphetamine users, substance use coping emerged as a common means of managing
      stress, especially for those with a history of CSA, which was further linked to
      depressive symptoms. These findings underscore the potential benefit of
      integrating coping interventions and mental health treatment into substance abuse
      treatment programs, particularly for those with a history of childhood abuse and
      violence. (PsycINFO Database Record

PMID- 27710006
TI  - A randomized clinical trial of a postdeployment parenting intervention for
      service members and their families with very young children.
AB  - OBJECTIVE: Parenting through the deployment cycle presents unique stressors for
      military families. To date, few evidence-based and military-specific parenting
      programs are available to support parenting through cycles of deployment
      separation and reintegration, especially for National Guard/Reserve members. The
      purpose of this research was to test the efficacy of a parenting program
      developed specifically to support military families during reintegration. METHOD:
      Within 1 year of returning from deployment to Afghanistan or Iraq, 115 service
      members with very young children were randomly assigned to receive either the
      Strong Families Strong Forces Parenting Program at baseline or after a 12-week
      waiting period. Using a home-based modality, service members, at-home parents,
      and their young child were assessed at baseline, 3 months posttreatment/wait
      period, and 6 months from baseline. RESULTS: Service member parents in Strong
      Families evidenced greater reductions in parenting stress and mental health
      distress relative to those in the waitlist comparison group. Service members with
      more posttraumatic stress symptoms reported higher levels of perceived parental
      efficacy in the intervention group than service members in the comparison group.
      Intervention also resulted in enhanced parental reflective capacity, including
      increased curiosity and interest in the young child among those in the
      intervention group relative to comparison. CONCLUSION: Service member parents and
      their spouses demonstrated high interest in participating in a postdeployment
      parenting program targeting families with very young children. Findings point to
      the feasibility, appeal, and efficacy of Strong Families in this initial trial
      and suggest promise for implementation in broader military and community service
      systems. (PsycINFO Database Record

PMID- 27710007
TI  - Intergenerational transmission of captivity trauma and posttraumatic stress
      symptoms: A twenty three-year longitudinal triadic study.
AB  - OBJECTIVES: The aversive, long-term toll of war captivity and fathers' combat
      induced posttraumatic stress disorder symptoms (PTSS) on adult offspring's mental
      health has been recently exemplified. However, studies that have examined the
      implication of PTSS of both fathers and mothers in the intergenerational
      transmission of trauma to offspring are still lacking. This prospective study
      assessed the unique and combined effects of former prisoners of war (ex-POWs)
      fathers' and mothers' PTSS in adult offspring's PTSS. METHOD: A sample of 123
      Israeli father-mother-offspring triads (79 ex-POW triads and a comparable group
      of 44 veteran triads) completed self-report measures. Following the 1973 Yom
      Kippur War, fathers participated in 3 waves of measurements (1991, 2003, 2008),
      mothers participated in 2 waves of measurements (2004, 2011), while offspring
      took part in 2014. RESULTS: Both fathers' and mothers' PTSS were positively
      related to offspring's PTSS. Among ex-POW triads, fathers' PTSS in 2003 and 2008
      and mothers' PTSS in 2004 predicted offspring's PTSS in 2014. Interestingly,
      serial multiple mediation model results showed that mothers' PTSS in 2004
      mediated the link between fathers' PTSS in 1991 and offspring's PTSS in 2014.
      Furthermore, fathers' PTSS in 2008 mediated the link between mothers' PTSS in
      2004 and offspring's PTSS in 2014. CONCLUSIONS: Over time, both ex-POWs fathers'
      and mothers' PTSS are implicated in their offspring's PTSS. However, both direct
      and indirect effects of both parents' posttraumatic reactions contribute to the
      intergenerational transmission of captivity related trauma. (PsycINFO Database
      Record

PMID- 27710008
TI  - Anticipatory fear and helplessness predict PTSD and depression in domestic
      violence survivors.
AB  - OBJECTIVE: Embracing the conceptual framework of contemporary learning theory,
      this study tested the hypothesis that anticipatory fear due to a sense of ongoing
      threat to safety and sense of helplessness in life would be the strongest
      determinants of PTSD and depression in domestic violence survivors. METHOD:
      Participants were 220 domestic violence survivors recruited consecutively from 12
      shelters for women in Turkey (response rate 70%). They were assessed with the
      Semi-Structured Interview for Survivors of Domestic Violence, Traumatic Stress
      Symptom Checklist, Depression Rating Scale, and Fear and Sense of Control Scale.
      RESULTS: Survivors were exposed to 21 (SD = 6.7) physical, psychological, and
      sexual violence stressors over 11.3 (SD = 8.8) years. They reported high levels
      of peritrauma perceived distress of and lack of control over stressor events.
      Approximately 10 months after trauma, many feared reliving the same domestic
      violence events, felt helpless, feared for their life, and felt in danger. PTSD
      and depression rates were 48.2% and 32.7%, respectively. The strongest predictors
      of PTSD and depression were fear due to a sense of ongoing threat to safety and
      sense of helplessness in life, which explained the largest amount of variances in
      these psychiatric conditions. CONCLUSION: The findings support the contemporary
      learning theory of traumatic stress and are consistent with findings of studies
      involving earthquake, war, and torture survivors. They imply that trauma-focused
      interventions designed to overcome fear, reduce helplessness, and restore sense
      of control over one's life would be effective in PTSD and depression in domestic
      violence survivors. (PsycINFO Database Record

PMID- 27710009
TI  - Effects of a brief education and treatment-planning group on evidence-based PTSD
      treatment utilization and completion among veterans.
AB  - OBJECTIVE: Veterans with posttraumatic stress disorder (PTSD) presenting for care
      with Veterans Affairs Health Care System (VA) tend not to engage in evidence
      based psychotherapies (EBPs) despite widespread availability of these treatments.
      Though there is little evidence that "readiness for treatment" affects treatment
      choice, many VA providers believe that interventions to increase readiness would
      be helpful. This naturalistic study examined the effects of a 4-session
      education/treatment-planning group on treatment choice among veterans in a VA
      outpatient PTSD treatment program. METHOD: Treatment choices and completion rates
      of 114 veterans who received at least 1 session of the group (EG) were compared
      with those of 68 veterans who did not receive the group and received PTSD program
      treatment as usual (TAU). TAU and EG cases were matched on gender and service
      era. RESULTS: Of 114 EG cases, 52 (45.6%) chose to receive EBPs, compared with 10
      of 68 TAU cases (14.7%). These rates were significantly different, chi2(1) =
      18.1, p < .0001. Among cases choosing EBPs, 52.2% of EG cases completed the EBPs
      as planned, compared with 60% of TAU cases. These percentages were not
      significantly different. Among EG cases choosing EBPs, lower likelihood of
      treatment completion was related to psychiatric medication prescription, presence
      of PTSD service connection, and higher overall service-connection level.
      CONCLUSION: The education/treatment-planning group was associated with higher
      likelihood of selecting but not completing EBPs for PTSD. The decision to engage
      in trauma-focused treatment may be a different process from the decision to
      complete such treatment. (PsycINFO Database Record

PMID- 27710012
TI  - Mechanistic Studies of Capsaicin-Induced Apnea in Rodents.
AB  - Inhalation of capsaicin-based sprays can cause central respiratory depression and
      lethal apneas. There are contradictory reports regarding the sites of capsaicin
      action. Furthermore, an understanding of the neurochemical mechanisms underlying
      capsaicin-induced apneas and the development of pharmacological interventions is
      lacking. The main objectives of this study were to perform a systematic study of
      the mechanisms of action of capsaicin-induced apneas and to provide insights
      relevant to pharmacological intervention. In vitro and in vivo rat and transient
      receptor potential vanilloid superfamily member 1 (TRPV1)-null mouse models were
      used to measure respiratory parameters and seizure-like activity in the presence
      of capsaicin and compounds that modulate glutamatergic neurotransmission.
      Administration of capsaicin to in vitro and in vivo rat and wild-type mouse
      models induced dose-dependent apneas and the production of seizure-like activity.
      No significant changes were observed in TRPV1-null mice or rat medullary slice
      preparations. The capsaicin-induced effects were inhibited by the TRPV1
      antagonist capsazepine, amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      receptor antagonists CNQX, NBQX, perampanel, and riluzole, a drug that inhibits
      glutamate release and increases glutamate uptake. The capsaicin-induced effects
      on breathing and seizure-like activity were accentuated by positive allosteric
      modulators of the AMPA receptors, CX717 and cyclothiazide. To summarize,
      capsaicin-induced apneas and seizure-like behaviors are mediated via TRPV1
      activation acting at lung afferents, spinal cord-ascending tracts, and medullary
      structures (including nucleus tractus solitarius). AMPA receptor-mediated
      conductances play an important role in capsaicin-induced apneas and seizure-like
      activity. A pharmaceutical strategy targeted at reducing AMPA receptor-mediated
      glutamatergic signaling may reduce capsaicin-induced deleterious effects.

PMID- 27710010
TI  - Predicting Severe Asthma Exacerbations in Children.

PMID- 27710011
TI  - Cystic Fibrosis: The Dawn of a New Therapeutic Era.

PMID- 27710013
TI  - Parent-Reported Bullying and Child Weight Gain between Ages 6 and 15.
AB  - BACKGROUND: Childhood bullying has long-term negative mental and physical health
      correlates, including weight gain and symptoms of depression. The purpose of this
      research is to examine whether bullying in the first year of school is associated
      with greater weight gain by early adolescence and whether adolescent depressive
      symptoms mediate this association. METHODS: Data were drawn from the Longitudinal
      Study of Australian Children. Children (N = 3929) were measured every 2 years;
      BMI and waist circumference were available from ages 4 to 15. Parents reported on
      bullying at age 6. Children reported on their depressive symptoms at ages 12-13.
      RESULTS: Participants who weighed in the obese category at age 4 had an over 50%
      increased risk of being bullied in school at age 6. Being bullied at age 6 was
      associated with excess weight gain between ages 6 and 15, defined as either BMI
      or waist circumference. Depressive symptoms at age 12 partially explained the
      association between bullying and increases in adiposity. None of the associations
      varied by gender. CONCLUSIONS: Similar to other forms of peer victimization,
      bullying early in school is associated with greater weight gain through early
      adolescence; depressive symptom is one mechanism that contributes to this
      association.

PMID- 27710014
TI  - CT-based follow-up following radiotherapy or radiochemotherapy for locally
      advanced head and neck cancer; outcome and development of a prognostic model for
      regional control.
AB  - OBJECTIVE: The purpose of this study was to make a prognostic model for regional
      relapse in head and neck cancer using clinical and CT parameters. METHODS: 183
      patients with lymph node-positive head and neck cancer were treated between 2002
      and 2012 with radiotherapy or concurrent chemoradiotherapy. CT studies pre- and
      post-treatment were reviewed for lymph node size and the presence of necrosis,
      extracapsular spread (ECS) and calcifications. For every patient, correlations
      with 3-year regional control (RC), metastasis-free survival (MFS), disease-free
      survival (DFS) and overall survival (OS) were made. RESULTS: 3-year outcome rates
      were as follows: local control of 84%, RC of 80%, MFS of 74%, DFS of 61% and OS
      of 63%. Pre-treatment nodal size and the presence of necrosis were associated
      with a poorer outcome. This was also the case for post-treatment lymph node size,
      the presence of necrosis and ECS. We developed a CT-based prognostic model for RC
      with an area under the curve of 0.78 (95% confidence interval 0.63; 0.85).
      CONCLUSION: We reached a good outcome in our patient cohort using a CT-based
      follow-up approach. A CT-based model was developed, which can aid in predicting
      RC. Advances in knowledge: A prognostic model is proposed, which can aid in
      predicting RC and the necessity for post-radiotherapy neck dissection using
      clinical parameters and parameters derived from the post-treatment CT study. This
      is the first article to propose a prognostic model for regional relapse in head
      and neck cancer based on these parameters.

PMID- 27710016
TI  - Reducing the wait for emergency surgery.
AB  - In contrast to the pattern of emergency admissions, emergency surgery, unless of
      extreme urgency, is often delayed until the routine cases of the day have been
      completed. This results in a backlog of cases waiting late into the night for
      operation, a practice that has been declared 'unacceptable' by the Royal College
      of Surgeons of England.

PMID- 27710017
TI  - Paediatric conference.
AB  - The venue for the postponed RCN Children in A&E (Within the RCN A&E Nursing
      Association) Annual Conference, Saturday, April 24 1999 will be The Education
      Centre, Birmingham Children's Hospital, Steelhouse Lane, Birmingham.

PMID- 27710015
TI  - Trends of Child's Weight Perception by Children, Parents, and Healthcare
      Professionals during the Time of Terminology Change in Childhood Obesity in the
      United States, 2005-2014.
AB  - OBJECTIVE: To investigate the changes on self- and parental weight perceptions
      and parental communication with healthcare professionals (HCPs) in the United
      States during the mid-2000s period when the terminology changed for
      classifications of childhood obesity/overweight. METHODS: A repeated cross
      sectional study was conducted with 6799 children aged 8-15 years with the
      National Health and Nutrition Examination Survey 2005-2014. BMI was calculated
      from objectively measured heights and weights, and children were classified as
      normal/underweight, overweight or obese, using the new terminology. Children
      reported their own weight status. Parents reported their child's weight status
      and reported how HCPs described their children's weight status. Logistic
      regressions were used to investigate changes in weight perceptions among
      overweight/obese children themselves and their parents and parental communication
      with HCPs about children's overweight/obesity status during the time of the
      terminology change. RESULTS: The proportion of parents told by HCPs about
      children's weight status increased for overweight children [6.8% in 2005-2006 to
      18.8% in 2013-2014, p for trend (ptrend = 0.02)], and marginally increased
      between 2005-2006 (37.1%) and 2007-2008 (45.4%) for obese children (p = 0.09).
      However, parental perceptions for obese/overweight children did not change. Also,
      obese children's weight perception did not change, and the proportion of
      overweight children who perceived their weight status accurately declined in 2005
      2012 (25.9%-16.4%, ptrend = 0.02). CONCLUSIONS: Although the terminology change
      about childhood obesity/overweight was associated with increased communication
      about child's weight status by HCPs, the accuracy of weight perceptions among
      obese/overweight children or their parents did not improve or declined.

PMID- 27710019
TI  - Parenting and flexiworking.
AB  - IN 1994, I was working as a grade E nurse in a busy 20 bed female surgical ward.
      Although I loved my work, I was delighted to find I was pregnant, and thought it
      a good time to consider my future job options.

PMID- 27710018
TI  - Essence of emergency nursing.
AB  - For many years researchers, theorists and academics have embarked on a quest to
      identify and describe what exactly nursing is. If nurses like Benner, Henderson
      and even Nightingale have grappled with the question then what chance have we, as
      clinical nurses, of solving this enigma? And if nursing, per se, is not well
      defined how can we ever hope to explain what emergency nursing is about?

PMID- 27710020
TI  - Challenging makeover.
AB  - A WORKING group of the RCN A&E Nursing Association is updating its highly
      successful Challenging the Boundaries document in light of changes over the last
      five years in emergency nursing.

PMID- 27710021
TI  - Noise trauma from air bags.
AB  - Air bags have contributed substantially to the safety of car occupants in road
      accidents, but concern exists that they may inflate unnecessarily in low speed
      crashes. Previous articles have reported eye, face, upper limb, and chest
      injuries caused by air bag inflation. In this report, researchers describe two
      cases of hearing loss and persistent tinnitus that may have resulted from air bag
      inflation in low speed collisions. Neither subject sustained other injuries.

PMID- 27710022
TI  - Events/information wanted.

PMID- 27710023
TI  - Frontliners.

PMID- 27710024
TI  - L30m effort to woo A&E nurses back.
AB  - A MULTIMILLION pound modernisation of A&E units will be a key part of the
      government's efforts to bring qualified nurses back into the NHS.

PMID- 27710026
TI  - A specialist team of A&E doctors and nurses establish emergency care units in
      Kosovo.
AB  - On June 12, 1999 NATO troops led by British paratroopers of 5 Airborne Brigade
      entered Kosovo and secured key military sites. This multinational operation (code
      named 'OP AGRICOLA') was in response to the ethnic cleansing of Kosovo-Albanians,
      and followed a sustained period of aerial attack in Kosovo and Serbia. The ground
      operation required substantial medical support, and the British hospital element
      was provided by 22 Field Hospital RAMC.

PMID- 27710025
TI  - Identification and Characterization of a Chloroplast-Targeted Obg GTPase in
      Dendrobium officinale.
AB  - Bacterial homologous chloroplast-targeted Obg GTPases (ObgCs) belong to the plant
      typical Obg group, which is involved in diverse physiological processes during
      chloroplast development. However, the evolutionarily conserved function of ObgC
      in plants remains elusive and requires further investigation. In this study, we
      identified DoObgC from an epiphytic plant Dendrobium officinale and demonstrated
      the characteristics of DoObgC. Sequence analysis indicated that DoObgC is highly
      conserved with other plant ObgCs, which contain the chloroplast transit peptide
      (cTP), Obg fold, G domain, and OCT regions. The C terminus of DoObgC lacking the
      chloroplast-targeting cTP region, DoObgCDelta1-160, showed strong similarity to
      ObgE and other bacterial Obgs. Overexpression of DoObgCDelta1-160 in Escherichia
      coli caused slow cell growth and an increased number of elongated cells. This
      phenotype was consistent with the phenotype of cells overexpressing ObgE.
      Furthermore, the expression of recombinant DoObgCDelta1-160 enhanced the cell
      persistence of E. coli to streptomycin. Results of transient expression assays
      revealed that DoObgC was localized to chloroplasts. Moreover, we demonstrated
      that DoObgC could rescue the embryotic lethal phenotype of the Arabidopsis obgc-t
      mutant, suggesting that DoObgC is a functional homolog to Arabidopsis AtObgC in
      D. officinale. Gene expression profiles showed that DoObgC was expressed in leaf
      specific and light-dependent patterns and that DoObgC responded to wounding
      treatments. Our previous and present studies reveal that ObgC has an
      evolutionarily conserved role in ribosome biogenesis to adapt chloroplast
      development to the environment.

PMID- 27710027
TI  - CBE awarded to DoH officer (england).
AB  - Julie Hartley-Jones, Department of Health (England) nursing officer with
      responsibilities for acute and specialist services including A & E, has been
      awarded a CBE in the New Year's honours list. Ms Hartley-Jones, who was awarded
      her CBE for services to renal nursing, is also a former president of the European
      Dialysis and Transplant Nurses Association/European Renal Care Association. She
      recently spoke at the RCN A & E Nursing Association Conference on 'Making a
      Difference' and has a keen interest in emergency nursing issues.

PMID- 27710028
TI  - Photographs and memories.
AB  - Even the most hardened emergency nurse will admit that there are few more
      distressing sights and experiences than a sudden infant death. The urgency of the
      crew bringing the infant in; the desperation of mothers who only a few hours
      before cuddled their baby in their arms; the sombre mood of staff who know that
      there can only be one outcome but who try anyway. It's a horrible experience for
      all concerned and everyone feels that even doing everything they could, they have
      still failed.

PMID- 27710029
TI  - Nurses win in pay round.
AB  - Pay rises of 3.4 per cent for most nurses and up to 7.8 per cent for 60,000 of
      the most experienced have been welcomed by nursing unions.

PMID- 27710030
TI  - Frontliners.

PMID- 27710032
TI  - We've caught up in more way than one.
AB  - Twenty years ago I embarked on a four month study tour of the mergency services
      in Canada and the United States. This tour was made possible through the
      generosity of the Florence Nightingale Foundation. This foundation provides
      annual scholarship awards that enable nurses to travel, broaden their knowledge
      and bring back to the UK new ideas to benefit patient care. My study tour took in
      four hospitals emergency departments in Canada and five in the US. I travelled
      the length and breadth of the two ountries and also spent time bserving three
      paramedic systems. was privileged to spend time in some the world's best known
      trauma care systems.

PMID- 27710031
TI  - Journal scan.
AB  - On August 15, 1998 a bomb exploded in the main street of Omagh, killing 29
      people, including nine children, and injuring over 300. The local hospital,
      Tyrone County Hospital, took most casualties into its small A&E department, and
      others were sent to the Erne Hospital in Enniskillen, 40 miles away. A postal
      questionnaire study of the health of all staff of Sperrin Lakeland Health and
      Social Care Trust, which covers both hospitals, took place four months later, and
      analyses are continuing. This paper presents findings on the 41 doctors who
      replied in terms of their levels of post-traumatic stress disorder.

PMID- 27710033
TI  - Praise for staff efforts.
AB  - THE SECRETARY of State for Health (England), Alan Milburn has praised emergency
      staff for their efforts over the Christmas and millennium period. He said: 'Quite
      simply, NHS staff have been brilliant. Despite pressures brought about by the
      special circumstances of the millennium, the NHS has responded magnificently.'
      The Department of Health provided the following millennium night summary for
      England.

PMID- 27710035
TI  - Using Variable-Length Aligned Fragment Pairs and an Improved Transition Function
      for Flexible Protein Structure Alignment.
AB  - With the rapid growth of known protein 3D structures in number, how to
      efficiently compare protein structures becomes an essential and challenging
      problem in computational structural biology. At present, many protein structure
      alignment methods have been developed. Among all these methods, flexible
      structure alignment methods are shown to be superior to rigid structure alignment
      methods in identifying structure similarities between proteins, which have gone
      through conformational changes. It is also found that the methods based on
      aligned fragment pairs (AFPs) have a special advantage over other approaches in
      balancing global structure similarities and local structure similarities.
      Accordingly, we propose a new flexible protein structure alignment method based
      on variable-length AFPs. Compared with other methods, the proposed method
      possesses three main advantages. First, it is based on variable-length AFPs. The
      length of each AFP is separately determined to maximally represent a local
      similar structure fragment, which reduces the number of AFPs. Second, it uses
      local coordinate systems, which simplify the computation at each step of the
      expansion of AFPs during the AFP identification. Third, it decreases the number
      of twists by rewarding the situation where nonconsecutive AFPs share the same
      transformation in the alignment, which is realized by dynamic programming with an
      improved transition function. The experimental data show that compared with
      FlexProt, FATCAT, and FlexSnap, the proposed method can achieve comparable
      results by introducing fewer twists. Meanwhile, it can generate results similar
      to those of the FATCAT method in much less running time due to the reduced number
      of AFPs.

PMID- 27710034
TI  - Salmonella Infection in Middle-Aged and Older Adults: Incidence and Risk Factors
      from the 45 and Up Study.
AB  - BACKGROUND: Salmonella infection is one of the most common foodborne bacterial
      pathogens, and causes a significant health burden globally. We investigated the
      incidence and risk factors for notification and hospitalization due to Salmonella
      infection in older adults. MATERIALS AND METHODS: We used the 45 and Up Study, a
      large-scale Australian prospective study of adults aged >=45 years, with record
      linkage to multiple databases for the years 2006-2012 to estimate the incidence
      of notification and hospitalization for Salmonella infection and estimate hazard
      ratios using Cox regression. RESULTS: Over a total follow-up of 1,120,242 person
      years, 333 adults had laboratory-confirmed Salmonella infection and 101 were
      hospitalized; the notification and hospitalization incidence were 29.7 (95%
      confidence interval [CI]: 26.9-33.3) and 9.0 (95% CI: 7.4-10.9) per 100,000
      person-years, respectively. The risk of Salmonella infection notification did not
      differ by age, but risk of hospitalization increased with age. Elderly males had
      the highest risk of infection-related hospitalization. The risk of notification
      was higher for those living in rural or remote areas (adjusted hazard ratio [aHR]
      1.7, 95% CI 1.3-2.2), those taking proton pump inhibitors (aHR 1.9, 95% CI 1.4
      2.4), and those reporting chicken/poultry intake at least seven times per week
      (aHR 3.2, 95% CI 1.3-7.9). CONCLUSIONS: Chicken consumption remains a significant
      risk factor for Salmonella infection, highlighting the importance of reducing
      contamination of poultry and improving food safety advice for older people.

PMID- 27710036
TI  - CD5-Positive Tracheal Mucosa-associated Lymphoid Tissue Lymphoma Presenting with
      Prandial Dyspnea.

PMID- 27710037
TI  - Classification of biodegradable materials using QSAR modelling with uncertainty
      estimation.
AB  - The ability to determine the biodegradability of chemicals without resorting to
      expensive tests is ecologically and economically desirable. Models based on
      quantitative structure-activity relations (QSAR) provide some promise in this
      direction. However, QSAR models in the literature rarely provide uncertainty
      estimates in more detail than aggregated statistics such as the sensitivity and
      specificity of the model's predictions. Almost never is there a means of
      assessing the uncertainty in an individual prediction. Without an uncertainty
      estimate, it is impossible to assess the trustworthiness of any particular
      prediction, which leaves the model with a low utility for regulatory purposes. In
      the present work, a QSAR model with uncertainty estimates is used to predict
      biodegradability for a set of substances from a publicly available data set.
      Separation was performed using a partial least squares discriminant analysis
      model, and the uncertainty was estimated using bootstrapping. The uncertainty
      prediction allows for confidence intervals to be assigned to any of the model's
      predictions, allowing for a more complete assessment of the model than would be
      possible through a traditional statistical analysis. The results presented here
      are broadly applicable to other areas of modelling as well, because the
      calculation of the uncertainty will clearly demonstrate where additional tests
      are needed.

PMID- 27710038
TI  - 9th Annual Symposium on Self-Monitoring of Blood Glucose, April 28-30, 2016,
      Madrid, Spain.
AB  - International experts in the field of diabetes and diabetes technology met in
      Madrid, Spain, for the 9th Annual Symposium on Self-Monitoring of Blood Glucose.
      The goal of these meetings is to establish a global network of experts, thus
      facilitating new collaborations and research projects to improve the lives of
      people with diabetes. The 2016 meeting comprised a comprehensive scientific
      program, parallel interactive workshops, and two keynote lectures.

PMID- 27710059
TI  - Survey finds a 'receptionist' triage system in A&E.
AB  - Receptionists in A&E are often involved in assessing and prioritising patients,
      in spite of ten years of a nurse triage system being in operation, a survey
      found.

PMID- 27710060
TI  - Communal bank of nurses.
AB  - A study which looked into using a communal bank of emergency nurses to cover A&E
      staff shortfalls found that 68 per cent of respondents would work on a communal
      bank between a neighbouring A&E service.

PMID- 27710048
TI  - FastBill: An Improved Tool for Prediction of Cis-Regulatory Modules.
AB  - Here, we provide a new software tool, called FastBill, for prediction of
      evolutionarily conserved cis-regulatory modules. It improves on the previous
      version of our program, called Billboard, by improving the statistical
      significance calculation. It is also faster than the original Billboard, allowing
      for large-scale analyses, including multiple informant species. We illustrate the
      utility of FastBill by performing a large-scale computational experiment of
      enhancer prediction in the promoter area of more than 150 Drosophila melanogaster
      genes that possess annotated experimentally verified enhancers. FastBill is
      written in Python and is freely available for download as a standalone tool.

PMID- 27710062
TI  - Childhood injury prevention prevalence.
AB  - The design of childhood injury prevention programmes has been hindered by a
      dearth of valid and reliable information on injury frequency, cause, and outcome.
      A number of local injury surveillance systems have been developed to address this
      issue. One example is CHIRPP (Canadian Hospitals Injury Reporting and Prevention
      Program), which has been imported into the A&E department at the Royal Hospital
      for Sick Children, Glasgow. This paper examines a year of CHIRPP data.

PMID- 27710061
TI  - Emergency oxygen therapy in COPD.
AB  - Known patients presenting to the A&E department with chronic obstructive
      pulmonary disease (COPD) 'often receive varying rates of oxygen', and most nurses
      were giving 'too much oxygen in some cases', a recent study has found.

PMID- 27710063
TI  - Permanent sequelae in sports injuries.
AB  - The aim of this Italian paper was to identify permanent sequelae after sports
      injuries in children and adolescents. In 1985, a prospective register was drawn
      up of all sports related injuries reported that year by the residents of Trieste,
      Italy aged 6-15 years. Moderate to severe injuries (scoring 2 on the abbreviated
      injury scale (AIS) were the object of a longitudinal clinical study. In 1988,
      30.9 per cent of the 220 subjects enrolled had sequelae and a further follow up
      study was undertaken in 1997.

PMID- 27710065
TI  - Un title.

PMID- 27710064
TI  - Price and reward.
AB  - 'Speakers at the RCN A&E conference had surpassed themselves', Association chair
      Lynda Holt said in her closing remarks: 'Their papers showed the need to use
      evidence based practice to advance patient care.

PMID- 27710066
TI  - Reluctance to use ALS skills in practice.
AB  - Despite considerable resources invested in training A&E nurses in advanced life
      support (ALS)?skills, nurses are still reluctant to use those skills in actual
      cardiac arrests, two nurses at Mil-ton Keynes General NHS Trust have found.

PMID- 27710068
TI  - A marriage of two minds.
AB  - The lecturer-practitioner role is a valid career option, despite recent adverse
      publicity about the nature of the job. That is the conclusion of two lecturer
      practitioners who combine academia with A&E shifts.

PMID- 27710067
TI  - Managing pain in patient's with signs of acute drug dependency.
AB  - A&E departments are sorely in need of management guidelines to help staff manage
      patients who present with the dual problem of severe pain and drug dependence.

PMID- 27710069
TI  - Trauma award.
AB  - A nurse who helped victims of one of the worst atrocities in the Northern Ireland
      conflict is to visit South Africa to learn how trauma patients are cared for
      there.

PMID- 27710070
TI  - Making a difference.
AB  - A couple of months ago, I passed one of those milestones that I suppose we all
      pass sooner or later if we stay in the profession. I am now just over half my
      life in nursing. Over the years though, I have often been asked why I didn't do
      medicine instead. After all, it's said 'you're fairly bright wouldn't you have
      been better off'. The simple truth is, and although it may not be fashionable to
      say it too often these days, I am really proud of being a nurse. If I knew when I
      was 18 what I know now, I would still have made the same choice of career, except
      with fewer doubts.

PMID- 27710071
TI  - NHS Direct is launch pad for responsibility and status.
AB  - NHS Direct will be the launch pad that will lead A&E nurses to be given more
      responsibilities and stature in the NHS, according to junior health minister Lord
      Philip Hunt.

PMID- 27710081
TI  - The Global Engagement in Care Convening: Recommended Actions to Improve Health
      Outcomes for People Living With HIV.
AB  - The National HIV AIDS Strategy (NHAS) calls for a more coordinated response to
      the HIV epidemic. The Global Engagement in Care Convening created a forum for
      domestic and international experts to identify best practices in HIV care. This
      manuscript summarizes the meeting discussions and recommendations from meeting
      notes and an audio recording of the meeting. Recommendations include: further
      standardization of performance goals and performance measures; additional
      research; a more robust system to support competing needs of clients receiving
      services; electronic information exchanges for HIV-related data; an expansion of
      the role of other health professionals to extend the capacity of physicians and
      other members of the care team; and revisions to current financing systems to
      increase reimbursement for and access to services that promote linkage to and
      retention in HIV care. The recommendations provide a unique example of "reverse
      technical assistance" and will inform U.S. program development, research, and
      policy.

PMID- 27710082
TI  - What Community-Based HIV Prevention Organizations Say About Their Role in
      Biomedical HIV Prevention.
AB  - Community-based organizations (CBOs) are critical to delivery of effective HIV
      prevention because of their reach to key populations. This online survey of a
      national sample of CBOs assessed their awareness of, interest in, and resources
      needed to provide nonoccupational postexposure prophylaxis (nPEP), preexposure
      prophylaxis (PrEP), and HIV treatment as prevention (TasP). One hundred seventy
      five CBOs participated: 87 clinical and 88 nonclinical CBOs. For nPEP, PrEP, and
      TasP, program managers reported that awareness was high (94%, 90%, 85%), meeting
      current client need was low (20%, 13%, 18%), and the likelihood of increasing
      their current provision with additional resources was somewhat high (62%, 64%,
      62%). Clinical CBOs were more prepared to support expansion of these biomedical
      interventions than nonclinical CBOs. Meeting the information, training, and
      resource needs of CBOs is critical for effective collaboration to reduce the
      number of new HIV infections through expanded delivery of PrEP, nPEP, and TasP.

PMID- 27710084
TI  - Erratum.

PMID- 27710083
TI  - Social Desirability Response Bias and Other Factors That May Influence Self
      Reports of Substance Use and HIV Risk Behaviors: A Qualitative Study of Drug
      Users in Vietnam.
AB  - The accuracy of self-report data may be marred by a range of cognitive and
      motivational biases, including social desirability response bias. The current
      study used qualitative interviews to examine self-report response biases among
      participants in a large randomized clinical trial in Vietnam. A sample of study
      participants was reinterviewed. The vast majority reported being truthful and
      emphasized the importance of rapport with the study staff for achieving veridical
      data. However, some stated that rapport may lead to under reporting of risk
      behaviors in order not to disappoint study staff. Other factors that appeared to
      influence accuracy of self-reports include fear that the information may be
      divulged, desire to enroll in the study, length of the survey, and memory. There
      are several methods that can be employed to reduce response biases, and future
      studies should systematically address response bias and include methods to assess
      whether approaches and survey items are effective in improving accuracy of self
      report data.

PMID- 27710085
TI  - Using Online Settings to Identify Gay and Bisexual Men Willing to Take or With
      Experience Taking PrEP: Implications for Researchers and Providers.
AB  - Given the ongoing HIV epidemic, it is essential to identify gay and bisexual men
      who are interested in starting PrEP as well as active PrEP users. We report on
      online survey data gathered over a 17-month period in 2014-2015 from gay and
      bisexual men identified through six sources of recruitment (n = 2903): Facebook,
      a hookup website, two geosocial-sexual networking apps (herein "App 1: Pop-up
      ads" and "App 2: Banner ads"), and two types of listservs (one focused on general
      gay nightlife, and one focused on gay sex parties). Willingness to take PrEP were
      as follows: sex party listservs (71.3%), both apps (69.8%), Facebook (67.6%),
      hookup website (65.2%), and nightlife listservs (50.5%). Experience having taken
      PrEP was as follows: sex party listservs (23.4%), App 2: Banner ads (22.5%),
      nightlife listservs (17.1) Facebook (14.2%), App 1: Pop-up ads (12.4%), and
      hookup website (2.1%). In multivariable modeling, willingness to go on PrEP was
      independently associated with being younger, single, a person of color, and
      having been tested for HIV in the past 12 months. Source of recruitment was
      largely unassociated with willingness to start PrEP. Number of recent male
      partners, number of recent condomless anal sex (CAS) events, and when data were
      collected (i.e., time in months) were not significantly associated with
      willingness to start PrEP. In multivariable models, experience having taken PrEP
      was positively associated with sexual identity as gay, number of recent male sex
      partners, number of recent CAS acts, being tested for HIV in the past 12 months,
      and time (in months). Experience taking PrEP varied greatly by recruitment
      source, suggesting both researchers and providers might be well served to utilize
      digital mediums to effectively identify these individuals; however, should do so
      with caution as not all digital options may prove fruitful.

PMID- 27710086
TI  - Determinants of HIV Transmission Risk Among HIV-Infected Persons Engaged in Care.
AB  - People living with HIV (PLWH) engaged in medical care represent an accessible
      group to focus HIV prevention efforts. In an analysis of 1,883 PLWH from 2007 and
      2015, we determined the proportion at risk of HIV transmission and identified
      factors associated with HIV transmission risk using multivariable mixed effects
      logistic regression models with random intercepts. HIV transmission risk was
      defined by an HIV viral load > 1,500 copies/mL and self-reported unprotected sex.
      We found that 174 (9.2%) individuals were at risk for HIV transmission at least
      once. Factors associated with HIV transmission risk included younger age
      (adjusted OR [95% CI] per decade decrease = 2.30 [1.84, 2.89]), illicit drug use
      (adjusted OR = 5.36 [3.02, 9.56]), depression (adjusted OR = 1.88 [1.10, 3.21]),
      and education <12th grade (adjusted OR = 2.05 [1.15, 3.67]). Thus, nearly 1 in 10
      HIV-infected individuals engaged in care between 2007 and 2015 were potentially
      at risk of transmitting HIV. Behavioral interventions to decrease HIV
      transmission should focus on younger, less educated patients who are depressed
      and actively using illicit drugs.

PMID- 27710087
TI  - ProjectHeartforGirls.com: Development of a Web-Based HIV/STD Prevention Program
      for Adolescent Girls Emphasizing Sexual Communication Skills.
AB  - This article describes the development of ProjectHeartforGirls.com , an
      interactive web-based program designed to improve sexual communication skills and
      reduce the risk of HIV/STDs among adolescent girls, a population at heightened
      risk for negative sexual health outcomes (Centers for Disease Control and
      Prevention, 2013). Although sexual communication is a critical predictor of safer
      sex among teens, there are few online interventions that target these skills as a
      central program component. We developed ProjectHeartforGirls.com to fill this
      gap. Program development involved (1) identifying the target population
      (ethnically diverse high school girls), (2) clarifying the theoretical foundation
      (Reasoned Action Model), (3) conducting formative qualitative research (n = 25
      girls), (4) drafting initial program content, (5) receiving ongoing feedback from
      a teen advisory board (n = 5 girls), (6) programming online content, and (7)
      conducting usability testing (n = 6 girls). These steps are described along with
      the final intervention product, which is currently being evaluated in a
      randomized controlled trial.

PMID- 27710090
TI  - Polarization-Based Medicine: Protests Against the Mayo-NCCIH Pain Guidance Evoke
      the Bigotry of the Political Season.

PMID- 27710089
TI  - The Uses of Texting in Sexual Relationships Scale: Associations With Risky Sexual
      Behavior Among At-Risk African American Emerging Adults.
AB  - Qualitative and quantitative research was used to create the Uses of Texting in
      Sexual Relationships scale. At-risk, predominantly African American emerging
      adults participated in qualitative interviews (N = 20) and quantitative surveys
      (N = 110) about their uses of text messaging within romantic and sexual
      relationships. Exploratory factor analysis of items generated from interviews
      resulted in four subscales: Sexting, Relationship Maintenance, Relationship
      Development, and Texting for Sexual Safety. Exploratory analyses indicated
      associations of Sexting with more instances of condomless sex, and Texting for
      Sexual Safety with fewer instances of condomless sex, which was moderated by
      relationship power. Further research on the connections between text messaging in
      relationships and sexual behavior among high-risk and minority young adults is
      warranted, and intervention efforts to decrease sexual risks need to incorporate
      these avenues of sexual communication.

PMID- 27710091
TI  - Evaluation of 2 Heat-Mitigation Methods in Army Trainees.
AB  - CONTEXT:  Heat injury is a significant threat to military trainees. Different
      methods of heat mitigation are in use across military units. Mist fans are 1 of
      several methods used in the hot and humid climate of Fort Benning, Georgia.
      OBJECTIVES:  To determine if (1) the mist fan or the cooling towel effectively
      lowered participant core temperature in the humid environment found at Fort
      Benning and (2) the mist fan or the cooling towel presented additional
      physiologic or safety benefits or detriments when used in this environment.
      DESIGN:  Randomized controlled clinical trial. SETTING:  Laboratory environmental
      chamber. PATIENTS OR OTHER PARTICIPANTS:  Thirty-five physically active men aged
      19 to 35 years. INTERVENTION(S):  (1) Mist fan, (2) commercial cooling towel, (3)
      passive-cooling (no intervention) control. All treatments lasted 20 minutes.
      Participants ran on a treadmill at 60% Vo2max. MAIN OUTCOME MEASURE(S):  Rectal
      core temperature, heart rate, thermal comfort, perceived temperature, perceived
      wetness, and blood pressure. RESULTS:  Average core temperature increased during
      20 minutes of cooling (F1,28 = 64.76, P < .001, etap2 = 0.70), regardless of
      group (F1,28 = 3.41, P = .08, etap2 = 0.11) or condition (F1,28 < 1.0). Core
      temperature, heart rate, and blood pressure did not differ among the 3
      conditions. Perceived temperature during 20 minutes of cooling decreased (F1,30 =
      141.19, P < .001, etap2 = 0.83) regardless of group or condition. Perceived
      temperature was lower with the mist-fan treatment than with the control treatment
      (F1,15 = 7.38, P = .02, etap2 = 0.32). The mist-fan group perceived themselves to
      be cooler even at elevated core temperatures. CONCLUSIONS:  The mist fan and
      cooling towel were both ineffective at lowering core temperature. Core
      temperature continued to increase after exercise in all groups. The mist fan
      produced feelings of coolness while the core temperature remained elevated,
      possibly increasing the risk of heat illness.

PMID- 27710093
TI  - A Comparison of Work Health and Safety Incidents and Injuries in Part-Time and
      Full-Time Australian Army Personnel.
AB  - CONTEXT:  Part-time personnel are an integral part of the Australian Army. With
      operational deployments increasing, it is essential that medical teams identify
      the patterns of injuries sustained by part-time personnel in order to mitigate
      the risks of injury and optimize deployability. OBJECTIVE:  To compare the
      patterns of reported work health and safety incidents and injuries in part-time
      and full-time Australian Army personnel. DESIGN:  Retrospective cohort study.
      SETTING:  The Australian Army. PATIENTS OR OTHER PARTICIPANTS:  Australian Army
      Reserve and Australian regular Army populations, July 1, 2012, through June 30,
      2014. MAIN OUTCOME MEASURE(S):  Proportions of reported work health and safety
      incidents that resulted in injuries among Army Reserve and regular Army personnel
      and specifically the (a) body locations affected by incidents, (b) nature of
      resulting injuries, (c) injury mechanisms, and (d) activities being performed
      when the incidents occurred. RESULTS:  Over 2 years, 15 065 work health and
      safety incidents and 11 263 injuries were reported in Army Reserve and regular
      Army populations combined. In the Army Reserve population, 85% of reported
      incidents were classified as involving minor personal injuries; 4% involved a
      serious personal injury. In the regular Army population, 68% of reported
      incidents involved a minor personal injury; 5% involved a serious personal
      injury. Substantially lower proportions of Army reservist incidents involved
      sports, whereas substantially higher proportions were associated with combat
      training, manual handling, and patrolling when compared with regular Army
      incidents. CONCLUSIONS:  Army reservists had a higher proportion of injuries from
      Army work-related activities than did regular Army soldiers. Proportions of
      incidents arising from combat tasks and manual handling were higher in the Army
      Reserve. Understanding the sources of injuries will allow the medical teams to
      implement injury-mitigation strategies.

PMID- 27710101
TI  - In touch.
AB  - Scotland's former rugby captain Gavin Hastings last month presented Margaret
      Ferguson with emergency equipment to help her provide care to the 180 island
      residents of Raasay, east of Skye. Ms Ferguson, a district nurse and midwife, is
      the only health care professional on the island. The bag of equipment, worth
      L1,000, has been produced by the British Association of Immediate Care (BASICS)
      Scotland and paid for by the Sandpiper Trust, established by the family of
      teenager Sandy Dickson, who drowned while on holiday in Canada.

PMID- 27710102
TI  - Emergency care tops the agenda at RCN Congress.
AB  - The future of A&E departments is at the top of the agenda of this year's RCN
      Congress.

PMID- 27710100
TI  - A randomized control trial evaluating fluorescent ink versus dark ink tattoos for
      breast radiotherapy.
AB  - OBJECTIVE: The purpose of this UK study was to evaluate interfraction
      reproducibility and body image score when using ultraviolet (UV) tattoos (not
      visible in ambient lighting) for external references during breast/chest wall
      radiotherapy and compare with conventional dark ink. METHODS: In this non
      blinded, single-centre, parallel group, randomized control trial, patients were
      allocated to receive either conventional dark ink or UV ink tattoos using
      computer-generated random blocks. Participant assignment was not masked.
      Systematic (?) and random (sigma) setup errors were determined using electronic
      portal images. Body image questionnaires were completed at pre-treatment, 1 month
      and 6 months to determine the impact of tattoo type on body image. The primary
      end point was to determine that UV tattoo random error (sigmasetup) was no less
      accurate than with conventional dark ink tattoos, i.e. <2.8 mm. RESULTS: 46
      patients were randomized to receive conventional dark or UV ink tattoos. 45
      patients completed treatment (UV: n = 23, dark: n = 22). sigmasetup for the UV
      tattoo group was <2.8 mm in the u and v directions (p = 0.001 and p = 0.009,
      respectively). A larger proportion of patients reported improvement in body image
      score in the UV tattoo group compared with the dark ink group at 1 month [56%
      (13/23) vs 14% (3/22), respectively] and 6 months [52% (11/21) vs 38% (8/21),
      respectively]. CONCLUSION: UV tattoos were associated with interfraction setup
      reproducibility comparable with conventional dark ink. Patients reported a more
      favourable change in body image score up to 6 months following treatment.
      Advances in knowledge: This study is the first to evaluate UV tattoo external
      references in a randomized control trial.

PMID- 27710092
TI  - Exploring the Perceptions of Newly Credentialed Athletic Trainers as They
      Transition to Practice.
AB  - CONTEXT: Research is limited on the transition to practice of newly credentialed
      athletic trainers (ATs). Understanding this transition could provide insight to
      assist employers and professional programs in developing initiatives to enhance
      the transition. OBJECTIVE: To explore newly credentialed ATs' experiences and
      feelings during their transition from student to autonomous practitioner. DESIGN:
      Qualitative study. SETTING: Individual phone interviews. PATIENTS OR OTHER
      PARTICIPANTS: Thirty-four ATs certified between January and September 2013
      participated in this study (18 women, 16 men; age = 23.8 +/- 2.1 years; work
      settings were collegiate, secondary school, clinic, and other). Data saturation
      guided the number of participants. DATA COLLECTION AND ANALYSIS: Participants
      were interviewed via phone using a semistructured interview guide. All interviews
      were recorded and transcribed verbatim. Data were analyzed through phenomenologic
      reduction, with data coded for common themes and subthemes. Credibility was
      established via member checks, peer review, and intercoder reliability. RESULTS:
      The 3 themes that emerged from the data were (1) transition to practice
      preparation, (2) orientation, and (3) mentoring. Transition to practice was
      rarely discussed during professional preparation, but information on the
      organization and administration or capstone course (eg, insurance, documentation)
      assisted participants in their transition. Participants felt that preceptors
      influenced their transition by providing or hindering the number and quality of
      patient encounters. Participants from larger collegiate settings reported more
      formal orientation methods (eg, review policies, procedures manual), whereas
      those in secondary school, clinic/hospital, and smaller collegiate settings
      reported informal orientation methods (eg, independent review of policies and
      procedures, tours). Some participants were assigned a formal mentor, and others
      engaged in peer mentoring. CONCLUSIONS: Employers could enhance the transition to
      practice by providing formal orientation and mentorship. Professional programs
      could prepare students for the transition by discussing how to find support and
      mentoring and by involving preceptors who provide students with opportunities to
      give patient care.

PMID- 27710104
TI  - Three heads are better than one?
AB  - Health minister with responsibility for emergency care Hazel Blears helped launch
      a L1.4 million NHS walk-in centre in St Helens, Merseyside, last month. As part
      of her tour of emergency services in the area, she met walk-in centre nurse
      clinician Sarah Chippington and patient Shaun Kenny. The nurse-led centre will
      help bring health, social and voluntary services under one roof.

PMID- 27710105
TI  - Spotlight on Casualty.
AB  - The BBC has come under fire for its portrayal in its TV drama, Casualty, of
      agency staff. Critics claim that temporary staff are shown as 'unhelpful, over
      paid, poorly trained and lacking the necessary insurance cover'.

PMID- 27710106
TI  - Better care for patients.
AB  - Emergency care is part of a system that is sensitive to emergency pressures.
      Reforming Emergency Care (DoH 2001) outlines the development of emergency care
      networks to facilitate and strengthen local partnership working, to ensure that
      the whole system is better able to cope with the demand for emergency care.

PMID- 27710108
TI  - Effectiveness of streamings.
AB  - This study aimed to assess whether a separate stream of minor injuries care in a
      UK A&E department decreases the waiting time, without delaying the care of those
      with more serious injury. A doctor saw any ambulant patients with injuries not
      requiring an examination couch or an urgent intervention, while patients
      requiring further treatment were returned to the sub-wait area until a nurse
      could see them. Data were retrospectively extracted from the routine hospital
      information systems for patients attending A&E for five weeks before the
      institution of the separate stream system and for five weeks after.

PMID- 27710109
TI  - Conference call.
AB  - The RCN A&E Nursing Association, Black Country A&E professional development group
      and University of Wolverhampton school of health are holding the Emergency
      Nursing Research 2002 conference on March 6 in Wolverhampton. For more
      information, contact Alastair Gray by phone on 01902 307999 ext 2055 or by email
      at a.d.gray@wlv.ac.uk. Details available at
      www.man.ac.uk/rcn/conference/enrc2002.doc.

PMID- 27710110
TI  - Fond farewell.
AB  - A&E sister Veronica McElroy has retired from the Ulster Hospital in Dundonald,
      where she has worked for 30 years.

PMID- 27710111
TI  - Are BTS guidelines followed?
AB  - In 1993, the British Thoracic Society (BTS) issued guidelines for the management
      of spontaneous pneumothorax. The study's aim was to determine the level of
      adherence to these guidelines at a London teaching hospital. A retrospective case
      note audit of 59 episodes was performed. In patients undergoing intervention, the
      initial procedure was simple aspiration in 32 (73 per cent) and chest tube
      insertion in 12 (27 per cent) cases, contrasting with the BTS recommendation that
      aspiration should be attempted first in all such patients. Simple aspiration was
      successful on 34 per cent of occasions. Successful aspiration was associated with
      a significantly shorter hospital stay (median 3, range 1-11 days) than either
      failed aspiration (7, 3-66 days) or chest tube insertion without aspiration (9, 3
      16 days). Other areas where practice differed from the BTS guidelines were
      clamping of chest tubes and use of a pursestring suture for wound closure. A
      follow up questionnaire suggested a lack of familiarity with the guidelines.
      These findings indicate that current management of spontaneous pneumothorax
      deviates from the BTS guidelines in potentially important respects.

PMID- 27710112
TI  - Plain ABDO X-rays: a waste of time?
AB  - Plain abdominal radiographs are commonly requested for acute medical emergencies
      on patients with non-specific abdominal symptoms and signs. In this study, 131
      plain abdominal radiographs performed on the day of admission were prospectively
      analysed by the research team. In only 16 cases (12 per cent) the reasons for
      requests conformed to the recommended guidelines by the Royal College of
      Radiologists. The reason for the request was stated in the case notes in only
      three cases. In 62 cases (47 per cent), there was no comment made on the film by
      the requesting clinician. There was a discrepancy in the interpretation of the
      radiograph between the clinician and the radiologist in 31 cases (24 per cent).
      The clinical management was influenced by plain abdominal radiographs in only
      nine cases (7 per cent). The researchers argue that most plain abdominal
      radiographs requested on acute medical emergencies are inappropriate. They
      suggest there is a need to ensure guidelines are followed to prevent unnecessary
      exposure of patients to radiation as well as preventing expenditure on irrelevant
      investigations.

PMID- 27710118
TI  - New guidance set for A&E service provision.
AB  - The new NHS Executive modernisation agency is set to publish guidelines on the
      provision of A&E services.

PMID- 27710115
TI  - Cross-Validation of Data Compatibility Between Small Angle X-ray Scattering and
      Cryo-Electron Microscopy.
AB  - Cryo-electron microscopy (EM) and small angle X-ray scattering (SAXS) are two
      different data acquisition modalities often used to glean information about the
      structure of large biomolecular complexes in their native states. A SAXS
      experiment is generally considered fast and easy but unveils the structure at
      very low resolution, whereas a cryo-EM experiment needs more extensive
      preparation and postacquisition computation to yield a three-dimensional (3D)
      density map at higher resolution. In certain applications, we may need to verify
      whether the data acquired in the SAXS and cryo-EM experiments correspond to the
      same structure (e.g., before reconstructing the 3D density map in EM). In this
      article, a simple and fast method is proposed to verify the compatibility of the
      SAXS and EM experimental data. The method is based on averaging the two
      dimensional correlation of EM images and the Abel transform of the SAXS data.
      Orientational preferences are known to exist in cryo-EM experiments, and we also
      consider these effects on our method. The results are verified on simulations of
      conformational states of large biomolecular complexes.

PMID- 27710119
TI  - 'Complacency' in training staff for major incidents.
AB  - Hospitals with no nurses trained in disaster management are 'sitting on a time
      bomb', the profession was warned at a recent conference.

PMID- 27710120
TI  - Web focus.
AB  - This regular feature highlights websites with useful information on clinical
      subjects. This edition focuses on international emergency nursing associations.

PMID- 27710122
TI  - Revised criteria for air ambulance service.
AB  - The NHS Executive North West has ordered an overhaul of guidance on air ambulance
      use following the death in 1999 of patient Julie Donaldson.

PMID- 27710124
TI  - Improved performance with training.
AB  - Nurse-specific training is better at equipping A&E nurses than generic training
      or experience alone, according to research from Belfast.

PMID- 27710123
TI  - Study findings back ENP care.
AB  - Ongoing research from Glasgow Royal Infirmary has provided further evidence that
      emergency nurse practitioners (ENPs) increase patient satisfaction while reducing
      waits.

PMID- 27710127
TI  - Co poisoning: A&E and hyperbaric unit documentation discrepancies.
AB  - The purpose of this study was to investigate and quantify the differences in
      neurological examination findings in patients acutely poisoned with carbon
      monoxide, between initial assessment at A&E departments and subsequently at a
      hyperbaric unit.

PMID- 27710125
TI  - ENP services need structural support.
AB  - Emergency nurse practitioner(ENP) services can only achieve full potential with
      broad structural support and staff development, the conference heard.

PMID- 27710128
TI  - Use of nitroglycerin in prehospital settings.
AB  - Nitroglycerin (NTG) is one of the most important medications used to treat
      ischaemic heart disease in both the prehospital and inpatient settings. The
      objective of this US study was to assess the effects of prehospital nitroglycerin
      (NTG) on vital signs and chest pain intensity.

PMID- 27710129
TI  - Frontliners.

PMID- 27710130
TI  - Examining Live-In Foreign Domestic Helpers as a Coping Resource for Family
      Caregivers of People With Dementia in Singapore.
AB  - In Singapore, the responsibility of caring for persons with dementia falls on
      family members who cope with a long-term caregiver burden, depending on available
      support resources. Hiring foreign domestic workers to alleviate caregiver burden
      becomes a prevalent coping strategy that caregivers adopt. This strategy allows
      caregivers to provide home care as part of fulfilling family obligations while
      managing the caregiver burden. This study aimed to investigate primary
      caregivers' relationship with hired support and its impact on coping with
      caregiver burden. Twenty in-depth interviews were conducted with primary
      caregivers who hired live-in domestic helpers to take care of their family
      members with dementia. The findings revealed that caregivers perceived the
      normative obligations to provide home care to family members with dementia. They
      sought support from domestic helpers to cope with physical and mental burnout,
      disruption of normal routines, and avoidance of financial strain. A mutual
      support relationship was built between caregivers and domestic helpers through
      trust and interdependence. The presence of domestic helpers as a coping resource
      reveals the positive outcomes of problem-, emotional-, and diversion-focused
      coping. This study illustrates that coping strategies are employed in different
      ways depending on the needs of caregivers, access to infrastructure, cultural
      expectations, and available resources.

PMID- 27710131
TI  - Erratum.

PMID- 27710132
TI  - Digital Natives Versus Digital Immigrants: Influence of Online Health Information
      Seeking on the Doctor-Patient Relationship.
AB  - Ubiquitous Internet access currently revolutionizes the way people acquire
      information by creating a complex, worldwide information network. The impact of
      Internet use on the doctor-patient relationship is a moving target that varies
      across sociodemographic strata and nations. To increase scientific knowledge on
      the patient-Web-physician triangle in Austria, this study reports findings
      regarding prevailing online health information-seeking behavior and the
      respective impact on doctor-patient interactions among a nonprobability
      convenience sample of Internet users. To investigate digital age group-specific
      influences, we analyzed whether digital natives and digital immigrants differed
      in their perspectives. The questionnaire-based online survey collected
      sociodemographic data and online health information-seeking behavior from a
      sample of 562 respondents (59% females, mean age 37 +/- 15 years, 54% digital
      natives). Most respondents (79%) referred to the Internet to seek health
      information, making it the most commonly used source for health information, even
      more prevalent then the doctor. We found similar predictors for using the
      Internet as a source for health-related information across digital age groups.
      Thus, the overall generational gap seems to be small among regular Internet users
      in Austria. However, study participants expressed a rather skeptical attitude
      toward electronic exchange of health data between health care professionals and
      patients, as well as toward reliability of online health information. To improve
      adoption of electronic doctor-patient communication and patient empowerment,
      public education and awareness programs are required to promote consumer-centered
      health care provision and patient empowerment.

PMID- 27710133
TI  - Identifying key areas for active interprofessional learning partnerships: A
      facilitated dialogue.
AB  - Student and service user involvement is recognised as an important factor in
      creating interprofessional education (IPE) opportunities. We used a team-based
      learning approach to bring together undergraduate health professional students,
      early career professionals (ECPs), public partners, volunteers, and carers to
      explore learning partnerships. Influenced by evaluative inquiry, this qualitative
      study used a free text response to allow participants to give their own opinion.
      A total of 153 participants (50 public partners and 103 students and
      professionals representing 11 healthcare professions) took part. Participants
      were divided into mixed groups of six (n = 25) and asked to identify areas where
      students, professionals, and public could work together to improve health
      professional education. Each group documented their discussions by summarising
      agreed areas and next steps. Responses were collected and transcribed for
      inductive content analysis. Seven key themes (areas for joint working) were
      identified: communication, public as partners, standards of conduct, IPE, quality
      improvement, education, and learning environments. The team-based learning format
      enabled undergraduate and postgraduate health professionals to achieve consensus
      with public partners on areas for IPE and collaboration. Some of our results may
      be context-specific but the approach is generalisable to other areas.

PMID- 27710134
TI  - Patient-reported and economic outcomes related to sofosbuvir and ledipasvir
      treatment for chronic hepatitis C.
AB  - INTRODUCTION: We used published literature from 2013-2016, to review data
      regarding the new all oral interferon and ribavirin free direct acting antiviral
      (DAA's) treatment regimens. Areas covered: Specifically, this paper will address
      DAA's clinical efficacy, their associated patient reported outcomes, their
      adherence to treatment, and their cost-effectiveness of treatment using studies
      from the United States. Expert commentary: The current data suggest that cure and
      elimination of HCV appears to be on the horizon; however, more research is needed
      to verify similar results from real world practices. Further, research is also
      needed to overcome the barriers to treatment (lack of education and awareness of
      HCV, inadequate diagnosis technology, and lack of access and link to care) in
      order for the elimination of HCV to be obtained.

PMID- 27710135
TI  - Pharmacodynamic and pharmacokinetic evaluation of insulin glargine U300 for the
      treatment of type 1 diabetes.
AB  - INTRODUCTION: Glargine 300 units/ml (Gla-300) is a novel basal insulin
      formulation approved in 2015 for the treatment of diabetes. This more
      concentrated form of glargine causes delayed redissolution from the subcutaneous
      depot after injection and thus altered action profile. Areas covered: The
      pharmacokinetics, pharmacodynamics, efficacy, and safety of Gla-300 in patients
      with type 1 diabetes mellitus (T1DM) will be reviewed. Expert opinion: Gla-300
      has a flatter and more prolonged pharmacokinetic profile compared to glargine 100
      units/ml (Gla-100), but is less potent on a unit per unit basis. The prolonged
      duration of Gla-300 should provide 24h coverage with a single daily dose in all
      patients. Two phase III trials comparing Gla-300 and Gla-100 were conducted in
      patients with T1DM. A1C reduction and other measures of glycemic control were
      similar between groups. Hypoglycemia rates were similar among groups in one
      trial, but favored Gla-300 in the other. Evidence for improvement in hypoglycemia
      with Gla-300 is more convincing in the type 2 diabetes population. Gla-300 is
      available in an insulin pen to mitigate potential dosing errors with different
      glargine concentrations; the maximum dose per injection is 80 units. Future
      research should include direct comparison with degludec and use in insulin
      resistant populations.

PMID- 27710136
TI  - Letter in response to "Idarucizumab for dabigatran overdose".

PMID- 27710137
TI  - Report on Provider-Client Interaction From 68 Methadone Maintenance Clinics in
      China.
AB  - Provider-client interaction is an integral of clinical practice and central to
      the delivery of high-quality medical care. This article examines factors related
      to the provider-client interaction in the context of methadone maintenance
      treatment (MMT). Data were collected from 68 MMT clinics in China. In total, 418
      service providers participated in the survey. Linear mixed effects regression
      models were performed to identify factors associated with provider-client
      interaction. It was observed that negative attitude toward drug users was
      associated with lower level of provider-client interaction and less time spent
      with each client. Other factors associated with lower level of interaction
      included being female, being younger, being a nurse, and fewer years in medical
      field. Higher provider-client interaction was associated with provider reported
      job satisfaction. The findings of this study call for a need to address provider
      negative attitudes that can impact provider-client interaction and the
      effectiveness of MMT. Future intervention efforts targeting MMT providers should
      be tailored by gender, provider type, and medical experiences.

PMID- 27710138
TI  - The Transformative Power of Authentic Conversations About Cancer.
AB  - Entertainment-education (E-E) assumes that actors performing content should be
      ethnically and culturally homogeneous with targeted audiences. The present study
      challenges this basic E-E assumption. Findings are presented from audience
      members who viewed When Cancer Calls... This theatrical production was
      constructed from verbatim transcriptions of naturally occurring telephone
      conversations between White family members as they communicated about and through
      their cancer journey. Non-White audience members were significantly more likely
      than White audience members to (a) regard the performance as authentic, (b) find
      it would influence "people like me," and (c) recommend the production to others.
      These findings suggest that all people must rely on communication when facing
      health challenges together. Such interactions that are fundamental to family
      membership are thus primal for the human social condition, regardless of
      differences in race and ethnicity. These findings also suggest innovative
      approaches to E-E health interventions that may contradict traditional market
      segmentation theories based on cultural differences and the principle of
      homophily.

PMID- 27710139
TI  - Higher pulse pressure/stroke volume index is associated with impaired outcome in
      hypertensive patients with left ventricular hypertrophy the LIFE study.
AB  - We tested the prognostic impact of a marker of arterial stiffness, pulse
      pressure/stroke volume index (PP/SVi), in patients with hypertension and left
      ventricular (LV) hypertrophy. We used data from 866 patients randomized to
      losartan or atenolol-based antihypertensive treatment, over a median of 4.8
      years, in the Losartan Intervention For Endpoint reduction in hypertension (LIFE)
      study. The association of PP/SVi with outcomes was tested in Cox regression
      analyses and reported as hazard ratio (HR) and 95% confidence intervals (CI). In
      multivariate regression, reduction of PP/SVi was independently associated with
      male gender, reduction in systolic blood pressure (BP) and relative wall
      thickness and with an increase in left ventricular ejection fraction (all p <
      .05). After adjusting for confounders, higher baseline PP/SVi predicted a 38%
      higher hazard of combined major fatal and non-fatal cardiovascular events (95% CI
      1.04-1.84), and higher hazard of cardiovascular mortality (HR 2.35 (95% CI 1.59
      3.48) and stroke (HR 1.45 (95% CI 1.06-1.99) (all p < .05). Higher PP/SVi also
      predicts higher rate of hospitalization for HF (HR 2.15 (95% CI 1.48-3.12) and a
      52% higher hazard of all-cause mortality (95% CI 1.10-2.09) (both p < .05). In
      hypertensive patients with electrocardiographic LV hypertrophy, higher PP/SVi was
      associated with increased cardiovascular morbidity and mortality.

PMID- 27710140
TI  - Risk factors and prophylaxis against invasive fungal disease for haematology and
      stem cell transplant recipients: an evolving field.
AB  - INTRODUCTION: Due to increasing intensity and complexity of therapies and longer
      survivorship, many patients with haematologic malignancy (HM) are at risk of
      invasive fungal disease (IFD). Mortality from IFD is high and treatment of an
      episode of IFD results in an excess length of hospital stay and costs and delays
      delivery of curative therapy of the underlying haematologic condition. Therefore,
      prevention and early recognition and treatment of IFD are crucial. Areas covered:
      Risk factors particular to certain HMs and haematopoietic stem cell
      transplantation, as well as those risk factors universal to all HM groups are
      examined. Expert commentary: Risk stratification identifies those patients who
      would benefit most from mould active versus yeast active prophylaxis and those
      who can be safely managed with monitoring and clinically driven interventions for
      IFD. This approach aids in antifungal stewardship.

PMID- 27710142
TI  - Corrigendum.

PMID- 27710141
TI  - Effects of phytoestrogens on bone mineral density during the menopause
      transition: a systematic review of randomized, controlled trials.
AB  - INTRODUCTION: Menopause is associated with increased bone resorption and
      decreased bone mineral density (BMD). Phytoestrogens are believed to prevent bone
      loss. This study reviewed relevant randomized, controlled trials to determine the
      effects of phytoestrogens on BMD in postmenopausal women. METHODS: In order to
      perform this systematic review, PubMed, Science Direct, Scopus, Cochrane Library,
      ISI Web of Knowledge, and ProQuest databases were searched for articles published
      during 2005-2016. The main keywords used during the searches were "phytoestrogen"
      and "bone mineral density" and "menopause". The Cochrane Risk of Bias Assessment
      Tool was used to evaluate the quality of the selected studies and to assess the
      risk of bias. RESULTS: A total of 23 eligible studies were included in this
      systematic review. Most selected studies used a double-blind, placebo-controlled
      design. In total, 3494 participants were enrolled in the selected trials.
      Different types of soy isoflavone extracts, including genistein extracts (either
      alone or in combination with daidzein), dietary products containing different
      amounts of phytoestrogens, and red clover extracts were used in the designed
      interventions. The duration of the interventions ranged from 7 weeks to 3 years.
      In most studies, the primary outcome was the efficacy of the designed
      intervention which was assessed through measuring whole body or regional BMD or
      bone mineral content, T-scores, and biomarkers of bone metabolism. CONCLUSIONS:
      Isoflavones probably have beneficial effects on bone health in menopausal women.
      Nevertheless, there were controversial reports about changes in BMD.
      Supplementation with a phytoestrogen can probably prevent the reduction in BMD
      and maintain a healthy bone structure during menopause.

PMID- 27710143
TI  - The future development of bacteria fighting medical devices: the role of graphene
      oxide.
AB  - INTRODUCTION: The clinical challenge that research on antibacterial coatings
      faces nowadays is the need of reduction of resistant bacterial infections, major
      source of implant rejection and repeated surgery. In order to avoid
      microorganisms attachment and biofilm formation, coating materials on medical
      devices have been developed with shortcomings represented by short-term
      durability and induction of new mechanisms of bacterial resistance. Graphene
      based films and hydrogel could represent the next generation protective coatings
      due to their excellent mechanical, chemical and thermal properties, high
      nanoparticle adsorption and antibacterial action. Areas covered: In this short
      commentary, we will report the recent developments of graphene oxide based
      coatings. Graphene oxide is a water-soluble derivative of graphene that allows
      high drug loading and miscibility with polymers, making it mouldable in any
      desired shape. Recent applications in wound healing and tissue engineering will
      be discussed as well as critical issues prior to clinical use of graphene oxide
      coatings. Expert commentary: The current evidence is insufficient to establish
      the efficacy of Graphene Oxide against bacteria and the durability of coatings.
      Further studies should clarify how to control Graphene Oxide antibacterial
      mechanism.

PMID- 27710145
TI  - Extreme Rapid Weight Loss and Rapid Weight Gain Observed in UK Mixed Martial Arts
      Athletes Preparing for Competition.
AB  - There is a lack of research documenting the weight-making practices of mixed
      martial-arts (MMA) competitors. The purpose of the investigation was to quantify
      the magnitude and identify the methods of rapid weight loss (RWL) and rapid
      weight gain (RWG) in MMA athletes preparing for competition. Seven athletes (mean
      +/- SD, age 24.6 +/- 3.5 yrs, body mass 69.9 +/- 5.7 kg, competitive experience
      3.1 +/- 2.2 yrs) participated in a repeated-measures design. Measures of dietary
      intake, urinary hydration status, and body mass were recorded in the week
      preceding competition. Body mass decreased significantly (p < .0005) from
      baseline by 5.6 +/- 1.4 kg (8 +/- 1.8%). During the RWG period (32 +/- 1 hr) body
      mass increased significantly (p < .001) by 7.4 +/- 2.8 kg (11.7 +/- 4.7%),
      exceeding RWL. Mean energy and carbohydrate intake were 3176 +/- 482 kcal?day-1
      and 471 +/- 124 g?day-1, respectively. At the official weigh-in 57% of athletes
      were dehydrated (1033 +/- 19 mOsmol?kg-1) and the remaining 43% were severely
      dehydrated (1267 +/- 47 mOsmol?kg-1). Athletes reported using harmful dehydration
      based RWL strategies, including sauna (43%) and training in plastic suits (43%).
      Results demonstrated RWG greater than RWL, this is a novel finding and may be
      attributable to the 32 hr duration from weigh-in till competition. The observed
      magnitude of RWL and strategies used are comparable to those which have
      previously resulted in fatalities. Rule changes which make RWL impractical should
      be implemented with immediate effect to ensure the health, safety and wellbeing
      of competitors.

PMID- 27710144
TI  - Lentiviral Vector Gene Transfer of Endostatin/Angiostatin for Macular
      Degeneration (GEM) Study.
AB  - Neovascular age-related macular degeneration (NVAMD) is a prevalent cause of
      vision loss. Intraocular injections of VEGF-neutralizing proteins provide
      benefit, but many patients require frequent injections for a prolonged period.
      Benefits are often lost over time due to lapses in treatment. New treatments that
      sustain anti-angiogenic activity are needed. This study tested the safety and
      expression profile of a lentiviral Equine Infectious Anemia Virus (EIAV) vector
      expressing endostatin and angiostatin (RetinoStat(r)). Patients with advanced
      NVAMD were enrolled at three centers in the United States, and the study eye
      received a subretinal injection of 2.4 * 104 (n = 3), 2.4 * 105 (n = 3), or 8.0 *
      105 transduction units (TU; n = 15). Each of the doses was well-tolerated with no
      dose-limiting toxicities. There was little or no ocular inflammation. There was
      one procedure-related serious adverse event (AE), a macular hole, which was
      managed without difficulty and resolved. There was a vector dose-related increase
      in aqueous humor levels of endostatin and angiostatin with high reproducibility
      among subjects within cohorts. Mean levels of endostatin and angiostatin peaked
      between 12 and 24 weeks after injection of 2.4 * 105 TU or 8.0 * 105 TU at 57-81
      ng/mL for endostatin and 15-27 ng/mL for angiostatin, and remained stable through
      the last measurement at week 48. Long-term follow-up demonstrated expression was
      maintained at last measurement (2.5 years in eight subjects and >4 years in two
      subjects). Despite an apparent reduction in fluorescein angiographic leakage that
      broadly correlated with the expression levels in the majority of patients, only
      one subject showed convincing evidence of anti-permeability activity in these
      late-stage patients. There was no significant change in mean lesion size in
      subjects injected with 8.0 * 105 TU. These data demonstrate that EIAV vectors
      provide a safe platform with robust and sustained transgene expression for ocular
      gene therapy.

PMID- 27710146
TI  - High Prevalence of Dehydration and Inadequate Nutritional Knowledge Among
      University and Club Level Athletes.
AB  - Although dehydration of >= 2% body weight (BW) loss significantly impairs
      endurance performance, dehydration remains prevalent among athletes and may be
      owing to a lack of knowledge in relation to fluid requirements. The aim of this
      study was to assess the hydration status of university/club level athletes (n =
      430) from a range of sports/activities (army officer cadet training; bootcamp
      training; cycling; Gaelic Athletic Association camogie, football and hurling;
      golf; hockey; netball; rugby; running (sprinting and endurance); Shotokan karate
      and soccer) immediately before and after training/competition and to assess their
      nutritional knowledge. Urine specific gravity (USG) was measured immediately
      before and after exercise and BW loss during exercise was assessed. Nutritional
      knowledge was assessed using a validated questionnaire. 31.9% of athletes
      commenced exercise in a dehydrated state (USG >1.020) with 43.6% of participants
      dehydrated posttraining/competition. Dehydration was particularly prevalent (>40%
      of cohort) among karateka, female netball players, army officer cadets, and
      golfers. Golfers that commenced a competitive 18 hole round dehydrated took a
      significantly higher number of strokes to complete the round in comparison with
      their euhydrated counterparts (79.5 ?+/- 2.1 vs. 75.7 ?+/- 3.9 strokes, p =
      .049). Nutritional knowledge was poor among participants (median total score
      [IQR]; 52.9% [46.0, 59.8]), albeit athletes who were euhydrated at the start of
      exercise had a higher overall score in comparison with dehydrated athletes (55.2%
      vs. 50.6%, p = .001). Findings from the current study, therefore, have
      significant implications for the education of athletes in relation to their
      individual fluid requirements around exercise.

PMID- 27710147
TI  - Seasonal Variation in Vitamin D Status in Elite Athletes: A Longitudinal Study.
AB  - Studies monitoring vitamin D status in athletes are seldom conducted for a period
      of 12 months or longer, thereby lacking insight into seasonal fluctuations. The
      objective of the current study was to identify seasonal changes in total 25
      hydroxyvitamin D (25(OH)D) concentration throughout the year. Fifty-two, mainly
      Caucasian athletes with a sufficient 25(OH)D concentration (>75 nmol/L) in June
      were included in this study. Serum 25(OH)D concentration was measured every three
      months (June, September, December, March, June). In addition, vitamin D intake
      and sun exposure were assessed by questionnaires at the same time points. Highest
      total 25(OH)D concentrations were found at the end of summer (113 +/- 26 nmol/L),
      whereas lowest concentrations were observed at the end of winter (78 +/- 30
      nmol/L). Although all athletes had a sufficient 25(OH)D concentration at the
      start of the study, nearly 20% of the athletes were deficient (<50 nmol/L) in
      late winter.

PMID- 27710148
TI  - Fluid Retention and Utility of Practical Hydration Markers to Detect Three Levels
      of Recovery Fluid Intake in Male Runners.
AB  - Runners are unlikely to consume fluid during training bouts increasing the
      importance of recovery rehydration efforts. This study assessed urine specific
      gravity (USG) responses following runs in the heat with different recovery fluid
      intake volumes. Thirteen male runners completed 3 evening running sessions
      resulting in approximately 2,200 ?+/- 300 ml of sweat loss (3.1 ?+/- 0.4% body
      mass) followed by a standardized dinner and breakfast. Beverage fluid intake
      (pre/postbreakfast) equaled 1,565/2,093 ml (low; L), 2,065/2,593 ml (moderate; M)
      and 2,565/3,356 mL (high; H). Voids were collected in separate containers.
      Increased urine output resulted in no differences (p > .05) in absolute mean
      fluid retention for waking or first postbreakfast voids. Night void averages
      excluding the first void postrun (1.025 ?+/- 0.008; 1.013 ?+/- 0.008; 1.006 ?+/-
      0.003), first morning (1.024 ?+/- 0.004; 1.015 ?+/- 0.005; 1.014 ?+/- 0.005), and
      postbreakfast (1.022 ?+/- 0.007; 1.014 ?+/- 0.007; 1.008 ?+/- 0.003) USG were
      higher (p < .05) for L versus M and H respectively and more clearly
      differentiated fluid intake volume between L and M than color or thirst
      sensation. Waking (r = -0.66) and postbreakfast (r = -0.71) USG were both
      significantly correlated (p < .001) with fluid replacement percentage, but not
      absolute fluid retention. Fluid intake M was reported as most similar to normal
      consumption (5.6 ?+/- 1.0 on 0-10 scale) after breakfast and equaled 122 ?+/- 16%
      of sweat losses. Retention data suggests consumption above this level is not
      warranted or actually practiced by most runners drinking ad libitum, but that
      periodic prerun USG assessment may be useful for coaches to detect runners that
      habitually consume low levels of fluids between training bouts in warm seasons.

PMID- 27710149
TI  - Heightened Exercise-Induced Oxidative Stress at Simulated Moderate Level Altitude
      vs. Sea Level in Trained Cyclists.
AB  - Altitude exposure can exaggerate the transient increase in markers of oxidative
      stress observed following acute exercise. However, these responses have not been
      monitored in endurance-trained cyclists at altitudes typically experienced while
      training. Endurance trained males (n = 12; mean (+/- SD) age: 28 +/- 4 years,
      VO2max 63.7 +/- 5.3 ml/kg/min) undertook two 75-min exercise trials at 70%
      relative VO2max; once in normoxia and once in hypobaric hypoxia, equivalent to
      2000m above sea level (hypoxia). Blood samples were collected before, immediately
      after and 2 h postexercise to assess plasma parameters of oxidative stress
      (protein carbonylation (PC), thiobarbituric acid reactive substances (TBARS),
      total antioxidant capacity (TAC) and catalase activity (CAT)). Participants
      cycled at 10.5% lower power output in hypoxia vs. normoxia, with no differences
      in heart rate, blood lactate or rating of perceived exertion observed. PC
      increased and decreased immediately after exercise in hypoxia and normoxia
      respectively (nmol/mg/protein: Normoxia-0.3 +/- 0.1, Hypoxia + 0.4 +/- 0.1; both
      p < .05). CAT increased immediately postexercise in both trials, with the
      magnitude of change greater in hypoxia (nmol/min/ml: Normoxia + 12.0 +/- 5.0,
      Hypoxia + 27.7 +/- 4.8; both p < .05). CAT was elevated above baseline values at
      2 h postexercise in Hypoxia only (Normoxia + 0.2 +/- 2.4, Hypoxia + 18.4 +/- 5.2;
      p < .05). No differences were observed in the changes in TBARS and TAC between
      hypoxia and normoxia. Trained male cyclists demonstrated a differential pattern/
      timecourse of changes in markers of oxidative stress following submaximal
      exercise under hypoxic vs. normoxic conditions.

PMID- 27710150
TI  - Dietary Protein Intake and Distribution Patterns of Well-Trained Dutch Athletes.
AB  - Dietary protein intake should be optimized in all athletes to ensure proper
      recovery and enhance the skeletal muscle adaptive response to exercise training.
      In addition to total protein intake, the use of specific proteincontaining food
      sources and the distribution of protein throughout the day are relevant for
      optimizing protein intake in athletes. In the present study, we examined the
      daily intake and distribution of various proteincontaining food sources in a
      large cohort of strength, endurance and team-sport athletes. Well-trained male
      (n=327) and female (n=226) athletes completed multiple web-based 24-hr dietary
      recalls over a 2-4 wk period. Total energy intake, the contribution of animal-
      and plant-based proteins to daily protein intake, and protein intake at six
      eating moments were determined. Daily protein intake averaged 108+/-33 and 90+/
      24 g in men and women, respectively, which corresponded to relative intakes of
      1.5+/-0.4 and 1.4+/-0.4 g/kg. Dietary protein intake was correlated with total
      energy intake in strength (r=0.71, p <.001), endurance (r=0.79, p <.001) and team
      sport (r=0.77, p <.001) athletes. Animal and plant-based sources of protein
      intake was 57% and 43%, respectively. The distribution of protein intake was 19%
      (19+/-8 g) at breakfast, 24% (25+/-13 g) at lunch and 38% (38+/-15 g) at dinner.
      Protein intake was below the recommended 20 g for 58% of athletes at breakfast,
      36% at lunch and 8% at dinner. In summary, this survey of athletes revealed they
      habitually consume > 1.2 g protein/kg/d, but the distribution throughout the day
      may be suboptimal to maximize the skeletal muscle adaptive response to training.

PMID- 27710151
TI  - Exertional Hyponatremia and Serum Sodium Change During Ultraendurance Cycling.
AB  - INTRODUCTION: Exertional hyponatremia (EH) during prolonged exercise involves all
      avenues of fluid-electrolyte gain and loss. Although previous research implicates
      retention of excess fluid, EH may involve either loss, gain, or no change of body
      mass. Thus, the etiology, predisposing factors, and recommendations for
      prevention are vague-except for advice to avoid excessive drinking. PURPOSE: This
      retrospective field study presents case reports of two unacquainted recreational
      cyclists (LC, 31y and AM, 39 years) who began exercise with normal serum
      electrolytes but finished a summer 164-km ride (ambient, 34?+/-5 degrees C) with
      a serum [Na+] of 130 mmol/L. METHODS: To clarify the etiology of EH, their pre-
      and post-exercise measurements were compared to a control group (CON) of 31
      normonatremic cyclists (mean ?+/- SD; 37?+/-6 years; 141?+/-3 mmol Na+/L).
      RESULTS: Anthropomorphic characteristics, exercise time, and post-exercise
      ratings of thermal sensation, perceived exertion and muscle cramp were similar
      for LC, AM and CON. These two hyponatremic cyclists consumed a large and similar
      volume of fluid (191 and 189 ml/kg), experienced an 11 mmol/L decrease of serum
      [Na+], reported low thirst sensations; however, LC gained 3.1 kg (+4.3% of body
      mass) during 8.9 hr of exercise and AM maintained body mass (+0.1kg, +0.1%,
      10.6h). In the entire cohort (n = 33), post-event serum [Na+] was strongly
      correlated with total fluid intake (R2 = 0.45, p < .0001), and correlated
      moderately with dietary sodium intake (R2=0.28, p = .004) and body mass change
      (R2 = 0.22, p = .02). Linear regression analyses predicted the threshold of EH
      onset (<135 mmol Na+/L) as 168 ml fluid/kg. CONCLUSIONS: The wide range of serum
      [Na+] changes (+6 to -11 mmol/L) led us to recommend an individualized
      rehydration plan to athletes because the interactions of factors were complex and
      idiosyncratic.

PMID- 27710152
TI  - Physician Oversight of Pediatric Care in Emergency Medical Services.

PMID- 27710153
TI  - Sex Difference in the Association Between Metabolic Syndrome and Left Ventricular
      Diastolic Dysfunction.
AB  - BACKGROUND: Sex-related differences in the influence of metabolic syndrome (MetS)
      on various cardiovascular diseases have been suggested. The aim of this study was
      to investigate the effect of sex on the association between MetS and left
      ventricular (LV) diastolic dysfunction in patients with suspected coronary artery
      disease (CAD). METHODS: Two hundred ten patients (105 men and age-matched 105
      women; mean age: 56.5 +/- 10.9 years) undergoing elective coronary angiography
      for the evaluation of CAD were studied. MetS was defined according to the
      International Diabetes Federation criteria. LV diastolic function was assessed
      using transthoracic echocardiography. RESULTS: The incidence of MetS was 23.8% in
      men and 14.3% in women (P = 0.079). The incidence of LV diastolic dysfunction was
      significantly different by MetS in women, but not in men. In multiple linear
      regression analyses, the number of MetS components was independently associated
      with septal e' velocity, E/e', and left atrial (LA) diameter in women (P < 0.05
      for each). In men, the number of MetS components was associated with only LA size
      in this analysis. As the number of components of MetS increased, septal e'
      velocity decreased proportionally in women (P < 0.001), but not in men (P =
      0.117). CONCLUSIONS: Among middle-aged and elderly Korean patients at high risk
      of CAD, the impact of MetS on LV diastolic dysfunction was more pronounced in
      women than in men. This suggests the important role of sex hormonal effects in
      the development of LV diastolic dysfunction in relation to MetS in this
      population.

PMID- 27710154
TI  - Personal Trainer Perceptions of Providing Nutrition Care to Clients: A
      Qualitative Exploration.
AB  - Personal trainers are well placed to provide basic nutrition care in line with
      national dietary guidelines. However, many personal trainers provide nutrition
      care beyond their scope of practice and this has been identified as a major
      industry risk due to a perceived lack of competence in nutrition. This paper
      explores the context in which personal trainers provide nutrition care, by
      understanding personal trainers' perceptions of nutrition care in relation to
      their role and scope of practice. Semistructured telephone interviews were
      conducted with 15 personal trainers working within Australia. Thematic analysis
      was used to identify key themes. All personal trainers reported to provide
      nutrition care and reported that nutrition care was an important component of
      their role. Despite this, many were unaware or uncertain of the scope of practice
      for personal trainers. Some personal trainers reported a gap between the
      nutrition knowledge they received in their formal education, and the knowledge
      they needed to optimally support their clients to adopt healthy dietary
      behaviors. Overall, the personal training context is likely to be conducive to
      providing nutrition care. Despite concerns about competence personal trainers
      have not modified their nutrition care practices. To ensure personal trainers
      provide nutrition care in a safe and effective manner, greater enforcement of the
      scope of practice is required as well as clear nutrition competencies or
      standards to be developed during training.

PMID- 27710155
TI  - Ability of the Physiologic Criteria of the Field Triage Guidelines to Identify
      Children Who Need the Resources of a Trauma Center.
AB  - BACKGROUND: There is limited research on how well the American College of
      Surgeons/Center for Disease Control and Prevention Guidelines for Field Triage of
      Injured Patients assist EMS providers in identifying children who need the
      resources of a trauma center. OBJECTIVE: To determine the accuracy of the
      Physiologic Criteria (Step 1) of the Field Triage Guidelines in identifying
      injured children who need the resources of a trauma center. METHODS: EMS
      providers who transported injured children 15 years and younger to pediatric
      trauma centers in 3 mid-sized cities were interviewed regarding patient
      demographics and the presence or absence of each of the Field Triage Guidelines
      criteria. Children were considered to have needed a trauma center if they had non
      orthopedic surgery within 24 hours, ICU admission, or died. This data was
      obtained through a structured hospital record review. The over- and under-triage
      rates and positive likelihood ratios (+LR) were calculated for the overall
      Physiologic Criteria and each individual criterion. RESULTS: Interviews were
      conducted for 5,610 pediatric patients; outcome data were available for 5,594
      (99.7%): 5% of all patients needed the resources of a trauma center and 19% met
      the physiologic criteria. Using the physiologic criteria alone, 51% of children
      who needed a trauma center would have been under-triaged and 18% would have been
      over-triaged (+LR 2.8, 95% CI 2.4-3.2). Glasgow Coma Score (GCS) < 14 had a +LR
      of 14.3 (95% CI 11.2-18.3), with EMS not obtaining a GCS in 4% of cases. 54% of
      those with an EMS GCS < 14 had an initial ED GCS < 14. Abnormal respiratory rate
      (RR) had a +LR of 2.2 (95% CI 1.8-2.6), with EMS not obtaining a RR in 5% of
      cases. 41% of those with an abnormal EMS RR had an abnormal initial ED RR.
      Systolic blood pressure (SBP) < 90 had a +LR of 3.5 (95% CI 2.5-5.1), with EMS
      not obtaining a SBP in 20% of cases. SBP was not obtained for 79% of children <1
      year, 46% 1-4 years, 7% 5-9 years, and 2% 10-15 years. A total of 19% of those
      with an EMS SBP < 90 had an initial ED SBP < 90. CONCLUSIONS: The Physiologic
      Criteria are a moderate predictor of trauma center need for children. Missing or
      inaccurate vital signs may be limiting the predictive value of the Physiologic
      Criteria.

PMID- 27710156
TI  - Treating Patients with Immediately Life-Threating Conditions Requiring Previously
      Prescribed Medications Not Routinely Carried by EMS.

PMID- 27710157
TI  - Palliative Care: Seeing Is Believing.

PMID- 27710158
TI  - Hypertriglyceridemia: the importance of identifying patients at risk.
AB  - This review aims to explain risk factors, consequences, and management strategies
      recommended for patients with hypertriglyceridemia. A search of PubMed was
      performed: 'Hypertriglyceridemia'[Majr], limited to English-language and
      published in the 5 years up to April 2016. Abstracts of the 680 results were
      screened for inclusion. Reference lists of publications included were also
      screened for inclusion. Approximately 25% of the United States population has
      elevated (>=150 mg/dL) triglycerides (TG) putting them at an increased risk of
      cardiovascular disease, non-alcoholic fatty liver disease, and pancreatitis. Risk
      factors for hypertriglyceridemia include genetics, lifestyle and diet, renal
      disease, endocrine disorders, and certain medications. Guidelines recommend that
      all patients with hypertriglyceridemia are advised on lifestyle modification to
      reduce TG to <150 mg/dL; a reduction in body weight of 5-10% can reduce TG by
      approximately 20%. For patients with TG <400 mg/dL, the primary goal is to reduce
      low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein
      cholesterol, with most guidelines recommending statin therapy. When TG is >=500
      mg/dL the primary goal is to reduce TG levels to lower the risk of pancreatitis.
      Statin therapy (if LDL-C is elevated) in combination with a fibrate, or long
      chain omega-3 fatty acid may be required. The Food and Drug Administration
      withdrew approval for niacin and some fibrates in combination with statins in
      April 2016 citing unfavorable benefit-risk profiles. With the increasing
      incidence of associated conditions (e.g. obesity, metabolic syndrome, and type 2
      diabetes mellitus), it is likely that primary care physicians will encounter more
      patients with hypertriglyceridemia.

PMID- 27710159
TI  - A population-based study on incidence rates, Lauren distribution, stage
      distribution, treatment, and long-term outcomes for gastric adenocarcinoma in
      Central Norway 2001-2011.
AB  - BACKGROUND: Population-based studies for gastric adenocarcinoma are scarce,
      particularly studies conducted within a defined geographical area with publicly
      available censuses that allow incidence rates to be calculated. MATERIAL AND
      METHODS: Population-based study in Central Norway from 2001 to 2011, covering a
      population of 636 000-680 000, respectively. Patients were identified through the
      Cancer Registry of Norway and the Norwegian Patient Register, and were
      characterized by data from individual electronic patient records. Outcomes were
      compared across the early and the late half of the study period. RESULTS: A total
      of 878 patients were identified with a median age of 76.2 years. The male to
      female ratio was 1.72. Annual world age-standardized incidence was 8.0/105 and
      3.6/105, respectively. The Lauren diffuse type was significantly more frequent
      among patients below 60 years, among females and for non-cardia cancers, compared
      to their counterparts (p < .001). The Lauren mixed type had a stable proportion
      of around 13% irrespective of age, sex or tumor location. Early gastric cancers
      (EGC) represented 8.3% of the cases, whereas 44% of all patients were diagnosed
      with metastatic disease. In males, the proportion of cardia cancers increased
      from 29.7% to 39.1% during the study period (p = .005). The five-year overall
      survival was 16%, and was substantially better for the Lauren intestinal type
      compared to the diffuse type, log-rank p = .003. The R0-R1 resection rate was
      39%, with a corresponding five-year survival of 40.9%. CONCLUSIONS: This study
      provides population-derived data lacking in hospital-based studies. Lauren
      categories with epidemiological aspects and clinical outcomes are displayed.
      Gastric cancer was associated with a dismal prognosis. Few patients had EGC and
      close to 50% had metastatic disease. Many were too old or frail to be considered
      for surgery.

PMID- 27710160
TI  - Treatment of Nonalcoholic Fatty Liver Disease with Long-Chain n-3 Polyunsaturated
      Fatty Acids in Humans.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for
      type 2 diabetes, cardiovascular disease, and liver failure. Treatment with n-3
      long-chain polyunsaturated fatty acids (n-3 LCPUFAs) produced variable success in
      improving NAFLD. The purpose of this review is to determine if n-3 LCPUFA will
      decrease markers of NAFLD, compare the efficacies of eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA), and identify factors that contribute to
      discrepancies in results. METHODS: This study reviewed published clinical studies
      with n-3 LCPUFA and NAFLD/nonalcoholic steatohepatitis (NASH) by using PubMed and
      Web of Science. RESULTS: Seventeen human studies ranging in DHA 250 mg/day to a
      mixture of EPA+DHA 50 mL/day for 8 weeks to 2 years were identified. Results
      obtained varied because of different dosages of n-3 LCPUFA, EPA and DHA ratios,
      duration, subject characteristics, diet, exercise, compliance, methods, and other
      factors. Despite inconsistencies in the results reported, 13 of 17 published
      studies reported that n-3 LCPUFA supplementation decreased liver fat, liver
      enzymes, or markers of inflammation; four reported decrease in ballooning and two
      in fibrosis. Results also indicated that DHA was more effective than EPA in the
      treatment of NAFLD. Caloric restriction and supplementation with n-3 LCPUFA were
      additive in decreasing hepatic steatosis. CONCLUSIONS: n-3 PUFA decreased several
      markers of NAFLD; however, there was a lower observed efficacy in NASH treatment.
      Further long-term placebo-controlled studies with adequate power and
      supplementation duration and standardized and sensitive detection methods are
      needed to determine the efficacy of EPA and DHA individually and in a mixture to
      treat NAFLD and NASH.

PMID- 27710161
TI  - Physician Oversight of Emergency Medical Services.

PMID- 27710162
TI  - Factors Associated with Breast Cancer Screening in a Country with National Health
      Insurance: Did We Succeed in Reducing Healthcare Disparities?
AB  - BACKGROUND: The effectiveness of breast cancer screening programs in reducing
      mortality is well established in the scientific literature. The National Breast
      Cancer Screening Program in Israel provides biennial mammograms for women of
      average risk aged 50-74 and annual mammograms for women aged 40-49 at higher
      risk. Compliance is high, but differential. This study explores different factors
      associated with breast cancer screening attendance among women aged 40-74 years.
      MATERIALS AND METHODS: Two main outcomes were studied: ever been screened and
      been screened in the 2 years preceding the study, using the cross-sectional
      Knowledge, Attitudes and Practices (KAP) Survey conducted in 2010-2012 among 2575
      Israeli women aged 21+ years. The independent variables were sociodemographic
      characteristics, perceived health status, lifestyle habits, and healthcare fund
      membership. Bivariate and multivariable logistic regressions were conducted.
      RESULTS: Of the 943 participants aged 50-74, 87% had ever been screened and 74.8%
      had attended screening for breast cancer in the last 2 years. In multivariable
      models, Jewish compared to Arab women (adjusted prevalence ratio [APR] = 2.09,
      95% confidence interval [CI]: 1.02-4.32), and unmarried compared to married women
      (APR = 2.9, 95% CI: 1.2-7.2), were more likely to have ever been screened. The
      only factor associated with breast cancer screening in the 2 years preceding the
      study was healthcare fund membership. In women aged 40-49 years, ethnicity was
      the only contributing factor associated with breast cancer screening, with higher
      screening rates in the 2 years preceding the study in Jewish versus Arab women
      (APR = 3.7, 95% CI: 1.52-9.3). CONCLUSIONS: Breast cancer screening attendance in
      Israel is high. However, significant differences are observed by membership of
      healthcare fund and by ethnicity, calling for better targeted outreach programs
      at this level.

PMID- 27710163
TI  - Defining a Bobath clinical framework - A modified e-Delphi study.
AB  - OBJECTIVE: To gain consensus within the expert International Bobath Instructors
      Training Association (IBITA) on a Bobath clinical framework on which future
      efficacy studies can be based. METHODS: A three-round modified e-Delphi approach
      was used with 204 full members of the IBITA. Twenty-one initial statements were
      generated from the literature. Consensus was defined a priori as at least 80% of
      the respondents with a level of agreement on a Likert scale of 4 or 5. The Delphi
      questionnaire for each round was available online for two weeks. Summary reports
      and subsequent questionnaires were posted within four weeks. RESULTS: Ninety-four
      IBITA members responded, forming the Delphi panel, of which 68 and 66 responded
      to Rounds Two and Three, respectively. The 21 initial statements were revised to
      17 statements and five new statements in Round Two in which eight statements were
      accepted and two statements were eliminated. Round Three presented 12 revised
      statements, all reaching consensus. CONCLUSION: The Delphi was successful in
      gaining consensus on a Bobath clinical framework in a geographically diverse
      expert association, identifying the unique components of Bobath clinical
      practice. Discussion throughout all three Rounds revolved primarily around the
      terminology of atypical and compensatory motor behavior and balance.

PMID- 27710164
TI  - An Ai Chi-based aquatic group improves balance and reduces falls in community
      dwelling adults: A pilot observational cohort study.
AB  - BACKGROUND: Falls are associated with morbidity, loss of independence, and
      mortality. While land-based group exercise and Tai Chi programs reduce the risk
      of falls, aquatic therapy may allow patients to complete balance exercises with
      less pain and fear of falling; however, limited data exist. OBJECTIVE: The
      objective of the study was to pilot the implementation of an aquatic group based
      on Ai Chi principles (Aquabalance) and to evaluate the safety, intervention
      acceptability, and intervention effect sizes. DESIGN: Pilot observational cohort
      study. METHODS: Forty-two outpatients underwent a single 45-minute weekly group
      aquatic Ai Chi-based session for eight weeks (Aquabalance). Safety was monitored
      using organizational reporting systems. Patient attendance, satisfaction, and
      self-reported falls were also recorded. Balance measures included the Timed Up
      and Go (TUG) test, the Four Square Step Test (FSST), and the unilateral Step
      Tests. RESULTS: Forty-two patients completed the program. It was feasible to
      deliver Aquabalance, as evidenced by the median (IQR) attendance rate of 8.0
      (7.8, 8.0) out of 8. No adverse events occurred and participants reported high
      satisfaction levels. Improvements were noted on the TUG, 10-meter walk test, the
      Functional Reach Test, the FSST, and the unilateral step tests (p < 0.05). The
      proportion of patients defined as high falls risk reduced from 38% to 21%. The
      study was limited by its small sample size, single-center nature, and the absence
      of a control group. CONCLUSIONS: Aquabalance was safe, well-attended, and
      acceptable to participants. A randomized controlled assessor-blinded trial is
      required.

PMID- 27710165
TI  - Dietary Intake, Body Composition, and Nutrition Knowledge of Australian Football
      and Soccer Players: Implications for Sports Nutrition Professionals in Practice.
AB  - Sports nutrition professionals aim to influence nutrition knowledge, dietary
      intake and body composition to improve athletic performance. Understanding the
      interrelationships between these factors and how they vary across sports has the
      potential to facilitate better-informed and targeted sports nutrition practice.
      This observational study assessed body composition (DXA), dietary intake
      (multiple-pass 24-hr recall) and nutrition knowledge (two previously validated
      tools) of elite and subelite male players involved in two team-based sports;
      Australian football (AF) and soccer. Differences in, and relationships between,
      nutrition knowledge, dietary intake and body composition between elite AF,
      subelite AF and elite soccer players were assessed. A total of 66 (23 ?+/- 4
      years, 82.0 ?+/- 9.2 kg, 184.7 ?+/- 7.7 cm) players participated. Areas of
      weaknesses in nutrition knowledge are evident (57% mean score obtained) yet
      nutrition knowledge was not different between elite and subelite AF and soccer
      players (58%, 57% and 56%, respectively, p > .05). Dietary intake was not
      consistent with recommendations in some areas; carbohydrate intake was lower (4.6
      ?+/- 1.5 g/kg/day, 4.5 ?+/- 1.2 g/kg/day and 2.9 ?+/- 1.1 g/kg/day for elite and
      subelite AF and elite soccer players, respectively) and protein intake was higher
      (3.4 ?+/- 1.1 g/kg/day, 2.1 ?+/- 0.7 g/kg/day and 1.9 ?+/- 0.5 g/kg/day for elite
      and subelite AF and elite soccer players, respectively) than recommendations.
      Nutrition knowledge was positively correlated with fat-free soft tissue mass (n =
      66; r2 = .051, p = .039). This insight into known modifiable factors may assist
      sports nutrition professionals to be more specific and targeted in their approach
      to supporting players to achieve enhanced performance.

PMID- 27710166
TI  - Professional roles in physiotherapy practice: Educating for self-management,
      relational matching, and coaching for everyday life.
AB  - The patient's active participation in treatment and rehabilitation represents a
      cultural change in clinical practice as well as a major change in physiotherapist
      and patient roles. This article presents findings from a study aimed at gaining a
      better understanding of how physiotherapists in actual practice understand their
      interactions with patients during the treatment process. This article reports on
      the findings from focus-group interviews with physiotherapists working in three
      different settings. Analyses of the interview data identified three modes of
      physiotherapy practice. In one, physiotherapists educate their patients to be
      self-managing in conducting exercise programs based on sound evidence.
      Educational films available on the Internet are included in these efforts to
      teach patients. In another, physiotherapists emphasize the importance of a close
      relationship to the patient. A good personal chemistry is believed to improve the
      treatment process. And finally, what physiotherapists learn about the living
      conditions and the biographies of their patients was shown to be very important.
      Understanding the importance of the life-world and taking this into consideration
      in the treatment process were factors considered to be central to good practice.
      The article concludes with a discussion linking these findings to those of other
      studies identifying those factors contributing to our knowledge of what is
      involved in biopsychosocial practice in physiotherapy.

PMID- 27710179
TI  - Polycyclic aromatic hydrocarbons in commercial brands of dry whole soybeans for
      direct human consumption.
AB  - A total of 13 polycyclic aromatic hydrocarbons (PAHs) were surveyed in dry whole
      soybeans (Glycine max L.) sold for human consumption. The analysed samples were
      commercialised in vegetarian shops and food stores in Southern Brazil regions.
      The determination of PAHs levels was carried out by high performance liquid
      chromatography (HPLC)with fluorescence detection. PAHs were present in 89.7% of
      the samples. Chrysene (Chy) and 5 methyl chrysene (5MeChy) were the main PAHs
      detected (76.9% and 71.8%, respectively) followed by dibenzo(ai)pyrene (DaiP),
      however in a much less percentage of samples (23.1%). Apart from those PAHs, also
      benzo(a)antracene (BaA), benzo(b)fluoranthene (BbF), benzo(k)fluoranthene (BkF)
      and benzo(a)pyrene(BaP) were found. The SigmaPAH levels in the positive samples
      ranged from 0.80 to 38.78 ug kg-1, with exception of one sample that reached
      204.46 ug kg-1 (SigmaPAHs of six compounds). Despite the present contamination
      there are no maximum limits set for PAHs in soybeans.

PMID- 27710180
TI  - Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans.
AB  - CONTEXT: No kinetic models presently exist which simulate the effect of chelation
      therapy on lead blood concentrations in lead poisoning. OBJECTIVE: Our aim was to
      develop a kinetic model that describes the kinetics of dimercaptosuccinic acid
      (DMSA; succimer), a commonly used chelating agent, that could be used in
      developing a lead chelating model. MATERIAL AND METHODS: This was a kinetic
      modelling study. We used a two-compartment model, with a non-systemic
      gastrointestinal compartment (gut lumen) and the whole body as one systemic
      compartment. The only data available from the literature were used to calibrate
      the unknown model parameters. The calibrated model was then validated by
      comparing its predictions with measured data from three different experimental
      human studies. RESULTS: The model predicted total DMSA plasma and urine
      concentrations measured in three healthy volunteers after ingestion of DMSA 10
      mg/kg. The model was then validated by using data from three other published
      studies; it predicted concentrations within a factor of two, representing inter
      human variability. CONCLUSIONS: A simple kinetic model simulating the kinetics of
      DMSA in humans has been developed and validated. The interest of this model lies
      in the future potential to use it to predict blood lead concentrations in lead
      poisoned patients treated with DMSA.

PMID- 27710181
TI  - Double-Edged Sword: Women with Breast Cancer Caring for a Spouse with Cancer.
AB  - BACKGROUND: Experiences in caregiving may affect further coping with illness. The
      aim of this study was to assess mortality risk among women diagnosed with breast
      cancer while caring for a male spouse who had been diagnosed with cancer before
      or at the time of their own diagnosis. PATIENTS AND METHODS: We used a historical
      prospective study of a nationally representative cohort that was assessed by the
      Israeli Central Bureau of Statistics 1995 census and followed until 2011. The
      study population was divided into 2 * 2 groups (according to a positive/negative
      cancer history of the male spouse before the time of breast cancer diagnosis of
      the women X spouse alive/dead). The analyses were adjusted for age, ethnicity,
      breast cancer staging, and time of diagnosis. RESULTS: A total of 14,429 cases of
      breast cancer and 3,400 deaths were reported during the study period. Mortality
      was not mediated by the spouse's survival at the time of breast cancer diagnosis
      of the women. However, decreased risk of death was seen in women with a positive
      spouse history of cancer when the spouse was alive at the time of diagnosis in
      women who were diagnosed with breast cancer stages II and III (hazard ratio =
      0.76, 95% CI: 0.59-0.98). CONCLUSION: Among a subset of women diagnosed with
      breast cancer, there is evidence of a significant protective association between
      a history of caregiving for cancer of a spouse who is alive at the time of self
      diagnosis and subsequent survival. Our findings support hypotheses concerning a
      positive experience of caregiving and emphasize the need to define the patient
      and the caregiver as an integrative "unit of care."

PMID- 27710197
TI  - Improved children's motor learning of the basketball free shooting pattern by
      associating subjective error estimation and extrinsic feedback.
AB  - This study aimed at assessing the interaction between subjective error estimation
      and frequency of extrinsic feedback in the learning of the basketball free
      shooting pattern by children. 10- to 12-year olds were assigned to 1 of 4 groups
      combining subjective error estimation and relative frequency of extrinsic
      feedback (33% * 100%). Analysis of performance was based on quality of movement
      pattern. Analysis showed superior learning of the group combining error
      estimation and 100% feedback frequency, both groups receiving feedback on 33% of
      trials achieved intermediate results, and the group combining no requirement of
      error estimation and 100% feedback frequency had the poorest learning. Our
      results show the benefit of subjective error estimation in association with high
      frequency of extrinsic feedback in children's motor learning of a sport motor
      pattern.

PMID- 27710196
TI  - Women's Contraceptive Preference-Use Mismatch.
AB  - BACKGROUND: Family planning research has not adequately addressed women's
      preferences for different contraceptive methods and whether women's contraceptive
      experiences match their preferences. METHODS: Data were drawn from the Women's
      Healthcare Experiences and Preferences Study, an Internet survey of 1,078 women
      aged 18-55 randomly sampled from a national probability panel. Survey items
      assessed women's preferences for contraceptive methods, match between methods
      preferred and used, and perceived reasons for mismatch. We estimated predictors
      of contraceptive preference with multinomial logistic regression models. RESULTS:
      Among women at risk for pregnancy who responded with their preferred method (n =
      363), hormonal methods (non-LARC [long-acting reversible contraception]) were the
      most preferred method (34%), followed by no method (23%) and LARC (18%).
      Sociodemographic differences in contraception method preferences were noted (p
      values <0.05), generally with minority, married, and older women having higher
      rates of preferring less effective methods, compared to their counterparts.
      Thirty-six percent of women reported preference-use mismatch, with the majority
      preferring more effective methods than those they were using. Rates of match
      between preferred and usual methods were highest for LARC (76%), hormonal (non
      LARC) (65%), and no method (65%). The most common reasons for mismatch were
      cost/insurance (41%), lack of perceived/actual need (34%), and method-specific
      preference concerns (19%). CONCLUSION: While preference for effective
      contraception was common among this sample of women, we found substantial
      mismatch between preferred and usual methods, notably among women of lower
      socioeconomic status and women using less effective methods. Findings may have
      implications for patient-centered contraceptive interventions.

PMID- 27710198
TI  - Not strange but not true: self-reported interest in a topic increases false
      memory.
AB  - People are more likely to recall both true and false information that is
      consistent with their pre-existing stereotypes, schemata and desires. In
      addition, experts in a particular field are more likely to experience false
      memory in relation to their area of expertise. Here, we investigate whether level
      of interest, as distinct from level of knowledge, and in the absence of self
      professed expertise, is associated with increased false memory. 489 participants
      were asked to rank 7 topics from most to least interesting. They were then asked
      if they remembered the events described in four news items related to the topic
      they selected as the most interesting and four items related to the topic
      selected as least interesting. In each case, three of the events depicted had
      really happened and one was fictional. A high level of interest in a topic
      increased true memories for the topic and doubled the frequency of false
      memories, even after controlling for level of knowledge. We interpret the results
      in the context of the source-monitoring framework and suggest that false memories
      arise as a result of interference from existing information stored in domain
      related schemata.

PMID- 27710199
TI  - Overconfidence across the psychosis continuum: a calibration approach.
AB  - INTRODUCTION: An 'overconfidence in errors' bias has been consistently observed
      in people with schizophrenia relative to healthy controls, however, the bias is
      seldom found to be associated with delusional ideation. Using a more precise
      confidence-accuracy calibration measure of overconfidence, the present study
      aimed to explore whether the overconfidence bias is greater in people with higher
      delusional ideation. METHODS: A sample of 25 participants with schizophrenia and
      50 non-clinical controls (25 high- and 25 low-delusion-prone) completed 30
      difficult trivia questions (accuracy <75%); 15 'half-scale' items required
      participants to indicate their level of confidence for accuracy, and the
      remaining 'confidence-range' items asked participants to provide lower/upper
      bounds in which they were 80% confident the true answer lay within. RESULTS:
      There was a trend towards higher overconfidence for half-scale items in the
      schizophrenia and high-delusion-prone groups, which reached statistical
      significance for confidence-range items. However, accuracy was particularly low
      in the two delusional groups and a significant negative correlation between
      clinical delusional scores and overconfidence was observed for half-scale items
      within the schizophrenia group. Evidence in support of an association between
      overconfidence and delusional ideation was therefore mixed. CONCLUSIONS: Inflated
      confidence-accuracy miscalibration for the two delusional groups may be better
      explained by their greater unawareness of their underperformance, rather than
      representing genuinely inflated overconfidence in errors.

PMID- 27710200
TI  - Innovations in EMS Fellow Education Abstracts.

PMID- 27710205
TI  - Meta-analysis of Egg Consumption and Risk of Coronary Heart Disease and Stroke.
AB  - The possible relationship between dietary cholesterol and cardiac outcomes has
      been scrutinized for decades. However, recent reviews of the literature have
      suggested that dietary cholesterol is not a nutrient of concern. Thus, we
      conducted a meta-analysis of egg intake (a significant contributor to dietary
      cholesterol) and risk of coronary heart disease (CHD) and stroke. A comprehensive
      literature search was conducted through August 2015 to identify prospective
      cohort studies that reported risk estimates for egg consumption in association
      with CHD or stroke. Random-effects meta-analysis was used to generate summary
      relative risk estimates (SRREs) for high vs low intake and stratified intake dose
      response analyses. Heterogeneity was examined in subgroups where sensitivity and
      meta regression analyses were conducted based on increasing egg intake. A 12%
      decreased risk (SRRE = 0.88, 95% confidence interval [CI], 0.81-0.97) of stroke
      was observed in the meta-analysis of 7 studies of egg intake (high vs low;
      generally 1/d vs <2/wk), with little heterogeneity (p-H = 0.37, I2 = 7.50). A
      nonstatistically significant SRRE of 0.97 (95% CI, 0.88-1.07, p-H = 0.67, I2 =
      0.00) was observed in the meta-analysis of 7 studies of egg consumption and CHD.
      No clear dose-response trends were apparent in the stratified intake meta
      analyses or the meta regression analyses. Based on the results of this meta
      analysis, consumption of up to one egg daily may contribute to a decreased risk
      of total stroke, and daily egg intake does not appear to be associated with risk
      of CHD. Key Teaching Points: * The role of egg consumption in the risk of stroke
      and coronary heart disease has come under scrutiny over many years. * A
      comprehensive meta-analysis of prospective cohort studies that reported risk
      estimates for egg consumption in association with CHD or stroke was performed on
      the peer-reviewed epidemiologic literature through August 2015. * Overall,
      summary associations indicate that intake of up to 1 egg daily may be associated
      with reduced risk of total stroke. * Overall, summary associations show no clear
      association between egg intake and increased or decreased risk of CHD. * Eggs are
      a relatively low-cost and nutrient-dense whole food that provides a valuable
      source of protein, essential fatty acids, antioxidants, choline, vitamins, and
      minerals.

PMID- 27710207
TI  - Do emotional stimuli enhance or impede recall relative to neutral stimuli? An
      investigation of two "false memory" tasks.
AB  - Many eyewitness memory situations involve negative and distressing events;
      however, many studies investigating "false memory" phenomena use neutral stimuli
      only. The aim of the present study was to determine how both the Deese-Roediger
      McDermott (DRM) procedure and the Misinformation Effect Paradigm tasks were
      related to each other using distressing and neutral stimuli. Participants
      completed the DRM (with negative and neutral word lists) and viewed a distressing
      or neutral film. Misinformation for the film was introduced and memory was
      assessed. Film accuracy and misinformation susceptibility were found to be
      greater for those who viewed the distressing film relative to the neutral film.
      Accuracy responses on both tasks were related, however, susceptibility to the DRM
      illusion and Misinformation Effect were not. The misinformation findings support
      the Paradoxical Negative Emotion (PNE) hypothesis that negative stimuli will lead
      to remembering more accurate details but also greater likelihood of memory
      distortion. However, the PNE hypothesis was not supported for the DRM results.
      The findings also suggest that the DRM and Misinformation tasks are not
      equivalent and may have differences in underlying mechanisms. Future research
      should focus on more ecologically valid methods of assessing false memory.

PMID- 27710209
TI  - Explaining the persistence of false memories: a proposal based on associative
      activation and thematic extraction.
AB  - This study aimed to analyse the effect of retention intervals on associative and
      thematic false memories. Two experiments, using two types of critical items that
      were either associatively or thematically related to studied material, were
      conducted. In both experiments, one group of participants performed a recognition
      test immediately after the presentation of lists, and another group performed the
      task one week later. In Experiment 1, the recognition test consisted of pairs of
      items with four response alternatives (both items had been presented, only the
      left item had been presented, only the right item had been presented or none of
      the items had been presented). Critical items were also manipulated so that they
      were either presented in or absent from the list. In Experiment 2, a standard
      recognition test that differed in the mode of presentation was used: self-paced
      or speeded response. Both experiments showed that associative critical items were
      more recognised than thematic critical items in the immediate condition. However,
      whereas associative critical items decayed after a one-week delay, thematic
      critical items were similarly recognised at both retention intervals. The
      findings of the present study suggest that each type of process - associative and
      thematic - behave differently over time.

PMID- 27710208
TI  - Growth Characteristics of Alkhumra Hemorrhagic Fever Virus in Mammalian Cell
      Lines.
AB  - BACKGROUND: Alkhumra hemorrhagic fever virus (AHFV) is a flavivirus that was
      discovered in 1995 in Saudi Arabia. Clinical manifestations of AHFV infection
      include hemorrhagic fever, hepatitis, and encephalitis with a reported mortality
      rate as high as 25%. There are no published data on the growth characteristics of
      AHFV in mammalian cell lines. The objective of this study was to examine the
      ability of AHFV to grow and propagate in four of the commonly used mammalian cell
      culture lines and to determine the virus growth curve characteristics in each.
      MATERIALS AND METHODS: Human epidermoid carcinoma (HEp-2), LLC-MK2, Madin-Darby
      canine kidney (MDCK), and Vero cell lines were inoculated with AHFV. The virus
      production by each cell line was determined by growth curve studies. Mean titers
      were calculated and expressed as median tissue culture infective dose per mL
      (TCID50/mL). RESULTS: AHFV grew and propagated to variable titers in the employed
      cell lines. The highest mean titers were observed in the LLC-MK2, followed by the
      MDCK, Vero, and HEP-2, in descending order. CONCLUSIONS: The growth curve studies
      showed that AHFV can propagate in the four types of cell lines to variable
      titers. LLC-MK2 cells are superior to MDCK, Vero, and HEP-2 for propagation of
      AHFV.

PMID- 27710211
TI  - Data on survival of recent births as a source of child mortality estimates in the
      developing world: An assessment of census data.
AB  - In many less developed countries, household surveys collect full and summary
      birth histories to provide estimates of child mortality. However, full birth
      histories are expensive to collect and cannot provide precise estimates for small
      areas, and summary birth histories only provide past child mortality trends. A
      simple method that provides estimates for the most recent past uses questions
      about the survival of recent births in censuses or large household surveys. This
      study examines such data collected by 45 censuses and shows that on average they
      tend to underestimate under-5 mortality in comparison with alternative estimates,
      albeit with wide variations. In addition, the high non-sampling uncertainty in
      this approach precludes its use in providing robust estimates of child mortality
      at the country level. Given these findings, we suggest that questions about the
      survival of recent births to collect data on child mortality not be included in
      census questionnaires.

PMID- 27710210
TI  - Bioactive Compounds and Antioxidant Properties of Goji fruits (Lycium barbarum
      L.) Cultivated in Serbia.
AB  - OBJECTIVE: Goji fruit extracts, methanol (MGE) and hexane (HGE), were subjected
      to evaluation as potential source of phenolic antioxidants and antiradical
      activity. METHODS: Some phenolic compounds (gallic, protocatechuic, vanillic,
      chlorogenic, coumaric, caffeic and ferulic acid and catechin and rutin), vitamin
      C and carotenoids were identified and quantified by HPLC. Antioxidant activity
      was tested by measuring ability to scavenge DPPH and hydroxyl radicals. Also,
      reducing power of goji fruit extracts was determined. RESULTS: HPLC analysis
      results showed predominance of gallic acid (40.44 mg/g g.f). Vitamin C content in
      MGE was 716.91 mg vitC/100 g g.f. IC50DPPH. varied from 26.64 MUmolTEAC/g for HGE
      to 62.15 MUmolTEAC/g for MGE, while RP0.5 values varied from 952.23 MUmolTEAC/g
      for MGE to 1360.48 mg/mL for HGE. IC50.OH for MGE was 1844.01 MUmolTEAC/g.
      CONCLUSIONS: Our results support the use of goji fruits as rich sources of
      phytochemicals for further utilization in the food industry as supplements and
      functional food ingredients.

PMID- 27710212
TI  - Trends and correlates of single motherhood in Kenya: Results from the Demographic
      and Health Survey.
AB  - Single motherhood exposes women to poorer socioeconomic and health outcomes,
      which may also negatively impact child outcomes. The Demographic and Health
      Surveys of 1989, 1993, 1998, 2003, and 2009 were used to investigate trends over
      time and factors associated with single motherhood in Kenya. Urban residence,
      older age, and poorer economic status were associated with single motherhood over
      time. Women with more than one child, and those with children under 15 years
      living at home were less likely to be single mothers. As women become single
      mothers at different stages, targeted and supportive strategies are required to
      mitigate associated risks.

PMID- 27710213
TI  - Two novel pyrrolooxazole pigments formed by the Maillard reaction between glucose
      and threonine or serine.
AB  - Pyrrolothiazolate formed by the Maillard reaction between l-cysteine and d
      glucose has a pyrrolothiazole skeleton as a chromophore. We searched for a
      Maillard pigment having a pyrrolooxazole skeleton formed from l-threonine or l
      serine instead of l-cysteine in the presence of d-glucose. As a result, two novel
      yellow pigments, named pyrrolooxazolates A and B, were isolated from model
      solutions of the Maillard reaction containing l-threonine and d-glucose, and l
      serine and d-glucose, respectively, and identified as (2R,3S,7aS)-2,3,7,7a
      tetrahydro-6-hydroxy-2,5,7a-trimethyl-7-oxo-pyrrolo[2,1-b]oxazole-3-calboxylic
      acid and (3S,7aS)-2,3,7,7a-tetrahydro-6-hydroxy-5,7a-dimethyl-7-oxo-pyrrolo[2,1
      b]oxazole-3-calboxylic acid by instrumental analyses. These compounds were
      pyrrolooxazole derivatives carrying a carboxy group, and showed the absorption
      maxima at 300-360 nm under acidic and neutral conditions and at 320-390 nm under
      alkaline conditions.

PMID- 27710214
TI  - "Telling our stories": Print media interpretations of Moscow lesbians' life
      stories in 2004 and 2005.
AB  - This article analyzes print media interviews of Moscow lesbians in Moskovsky
      Komsomolets in 2004 and 2005 using qualitative content analysis. The qualitative
      content analysis shows recurring and consistent themes: (1) the stereotypes
      lesbians face; (2) public negativity toward same-sex relations and the impact on
      their families; (3) the expectations of heterosexuality and all that that
      entails; (4) the existence of lesbian-only spaces in Russia and the importance of
      those spaces; and (5) the complexities of navigating motherhood, previous
      heterosexual relationships, and current partnerships. Analysis of print media
      representations of female same-sex sexuality in a period of economic prosperity,
      popular culture visibility, and before restrictive laws were passed that suppress
      homosexuality adds to the previous literature on lesbianism in Russia.

PMID- 27710239
TI  - Free Radical-derived Oxysterols: Novel Adipokines Modulating Adipogenic
      Differentiation of Adipose Precursor Cells.
AB  - CONTEXT: Increased oxidative stress in adipose tissue emerges as an inducer of
      obesity-linked insulin resistance. Here we tested whether free-radical derived
      oxysterols are formed by, and accumulate in, human adipocytes. Moreover, we asked
      whether increased accumulation of oxysterols characterizes the adipose cells of
      obese patients with type 2 diabetes (T2D) (OBT2D) compared with lean, nondiabetic
      controls (CTRLs). Finally, we studied the effects of the free radical-derived
      oxysterols on adipogenic differentiation of adipose-derived stem cells (ASCs).
      MAIN OUTCOME MEASURES: Adipocytes and ASCs were isolated from sc abdominal
      adipose tissue biopsy in four OBT2D and four CTRL subjects. Oxysterols in
      adipocytes were detected by gas chromatography/mass spectrometry. The cellular
      and molecular effects of oxysterols were then evaluated on primary cultures of
      ASCs focusing on cell viability, adipogenic differentiation, and "canonical" WNT
      and MAPK signaling pathways. RESULTS: 7-ketocholesterol (7kappa-C) and 7beta
      hydroxycholesterol were unambiguously detected in adipocytes, which showed higher
      oxysterol accumulation (P < .01) in OBT2D, as compared with CTRL individuals.
      Notably, the accumulation of oxysterols in adipocytes was predicted by the
      adipose cell size of the donor (R2 = 0.582; P < .01). Challenging ASCs with free
      radical-derived type I (7kappa-C) and type II (5,6-Secosterol) oxysterols led to
      a time- and concentration-dependent decrease of cell viability. Meaningfully, at
      a non-toxic concentration (1MUM), these bioactive lipids hampered adipogenic
      differentiation of ASCs by sequential activation of WNT/beta-catenin, p38-MAPK,
      ERK1/2, and JNK signaling pathways. CONCLUSION: Free radical-derived oxysterols
      accumulate in the "diabetic" fat and may act as novel adipokines modulating the
      adipogenic potential of undifferentiated adipose precursor cells.

PMID- 27710242
TI  - Metabolic Fingerprints of Circulating IGF-1 and the IGF-1/IGFBP-3 Ratio: A
      Multifluid Metabolomics Study.
AB  - OBJECTIVE: IGF-1 is known for its various physiological and severe
      pathophysiological effects on human metabolism; however, underlying molecular
      mechanisms still remain unsolved. To reveal possible molecular mechanisms
      mediating these effects, for the first time, we associated serum IGF-1 levels
      with multifluid untargeted metabolomics data. METHODS: Plasma/urine samples of
      995 nondiabetic participants of the Study of Health in Pomerania were
      characterized by mass spectrometry. Sex-specific linear regression analyses were
      performed to assess the association of IGF-1 and IGF-1/IGF binding protein 3
      ratio with metabolites. Additionally, the predictive ability of the plasma and
      urine metabolome for IGF-1 was assessed by orthogonal partial least squares
      analyses. RESULTS AND CONCLUSIONS: We revealed a multifaceted image of associated
      metabolites with large sex differences. Confirming previous reports, we detected
      relations between IGF-1 and steroid hormones or related intermediates.
      Furthermore, various associated metabolites were previously mentioned regarding
      IGF-1-associated diseases, eg, betaine and cortisol in cardiovascular disease and
      metabolic syndrome, lipid disorders, and diabetes, or have previously been found
      to associate with differentiation and proliferation or mitochondrial
      functionality, eg, phospholipids. bradykinin, fatty acid derivatives, and
      cortisol, which were inversely associated with IGF-1, might establish a link of
      IGF-1 with inflammation. For the first time, we showed an association between IGF
      1 and pipecolate, a metabolite linked to amino acid metabolism. Our study
      demonstrates that IGF-1 action on metabolism is tractable, even in healthy
      subjects, and that the findings provide a solid basis for further
      experimental/clinical investigation, eg, searching for inflammatory or
      cardiovascular disease- or metabolic syndrome-associated biomarkers and
      therapeutic targets.

PMID- 27710240
TI  - Differences in Mitochondrial Coupling Reveal a Novel Signature of Mitohormesis in
      Muscle of Healthy Individuals.
AB  - CONTEXT: Reduced mitochondrial coupling (ATP/O2 [P/O]) is associated with
      sedentariness and insulin resistance. Interpreting the physiological relevance of
      P/O measured in vitro is challenging. OBJECTIVE: To evaluate muscle mitochondrial
      function and associated transcriptional profiles in nonobese healthy individuals
      distinguished by their in vivo P/O. DESIGN: Individuals from an ancillary study
      of Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy
      phase 2 were assessed at baseline. SETTING: The study was performed at Pennington
      Biomedical Research Center. PARTICIPANTS: Forty-seven (18 males, 26-50 y of age)
      sedentary, healthy nonobese individuals were divided into 2 groups based on their
      in vivo P/O. INTERVENTION: None. Main Outcome(s): Body composition by dual-energy
      x-ray absorptiometry, in vivo mitochondrial function (P/O and maximal ATP
      synthetic capacity) by 31P-magnetic resonance spectroscopy and optical
      spectroscopy were measured. A muscle biopsy was performed to measure fiber type,
      transcriptional profiling (microarray), and protein expressions. RESULTS: No
      differences in body composition, peak aerobic capacity, type I fiber content, or
      mitochondrial DNA copy number were observed between the 2 groups. Compared with
      the uncoupled group (lower P/O), the coupled group (higher P/O) had higher rates
      of maximal ATP synthetic capacity (maximal ATP synthetic capacity, P < .01).
      Transcriptomics analyses revealed higher expressions of genes involved in
      mitochondrial remodeling and the oxidative stress response in the coupled group.
      A trend for higher mitonuclear protein imbalance (P = .06) and an elevated
      mitochondrial unfolded protein response (heat shock protein 60 protein; P = .004)
      were also identified in the coupled group. CONCLUSIONS: Higher muscle
      mitochondrial coupling is accompanied by an overall elevation in mitochondrial
      function, a novel transcriptional signature of oxidative stress and mitochondrial
      remodeling and indications of an mitochondrial unfolded protein response.

PMID- 27710243
TI  - ACAN Gene Mutations in Short Children Born SGA and Response to Growth Hormone
      Treatment.
AB  - Background: Some children born small for gestational age (SGA) show advanced bone
      age (BA) maturation during growth hormone (GH) treatment. ACAN gene mutations
      have been described in children with short stature and advanced BA. Objective: To
      determine the presence of ACAN gene mutations in short SGA children with advanced
      BA and assess the response to GH treatment. Methods: BA assessment in 290 GH
      treated SGA children. ACAN sequencing in 29 children with advanced BA >=0.5 years
      compared with calendar age. Results: Four of 29 SGA children with advanced BA had
      an ACAN gene mutation (13.8%). Mutations were related to additional
      characteristics: midface hypoplasia (P = 0.003), joint problems (P = 0.010), and
      broad great toes (P = 0.003). Children with one or fewer additional
      characteristic had no mutation. Of children with two additional characteristics,
      50% had a mutation. Of children with three additional characteristics, 100% had a
      mutation. All GH-treated children with a mutation received gonadotropin-releasing
      hormone analog (GnRHa) treatment for 2 years from onset of puberty. At adult
      height, one girl was 5 cm taller than her mother and one boy was 8 cm taller than
      his father with the same ACAN gene mutation. Conclusion: This study expands the
      differential diagnosis of genetic variants in children born SGA and proposes a
      clinical scoring system for identifying subjects most likely to have an ACAN gene
      mutation. ACAN sequencing should be considered in children born SGA with
      persistent short stature, advanced BA, and midface hypoplasia, joint problems, or
      broad great toes. Our findings suggest that children with an ACAN gene mutation
      benefit from GH treatment with 2 years of GnRHa.

PMID- 27710241
TI  - Randomized Trial of Aromatase Inhibitors, Growth Hormone, or Combination in
      Pubertal Boys with Idiopathic, Short Stature.
AB  - CONTEXT: Growth of short children in puberty is limited by the effect of estrogen
      on epiphyseal fusion. OBJECTIVES: To compare: 1) the efficacy and safety of
      aromatase inhibitors (AIs) vs GH vs AI/GH on increasing adult height potential in
      pubertal boys with severe idiopathic short stature (ISS); and 2) differences in
      body composition among groups. DESIGN: Randomized three-arm open-label
      comparator. SETTING: Outpatient clinical research. PATIENTS: Seventy-six pubertal
      boys [mean (SE) age, 14.1 (0.1) years] with ISS [height SD score (SDS), -2.3
      (0.0)]. INTERVENTION: Daily AIs (anastrozole or letrozole), GH, or AI/GH for 24
      36 months. OUTCOMES: Anthropometry, bone ages, dual x-ray absorptiometry, spine x
      rays, hormones, safety labs. RESULTS: Height gain [mean (SE)] at 24 months was:
      AI, +14.0 (0.8) cm; GH, +17.1 (0.9) cm; AI/GH, +18.9 (0.8) cm (P < .0006,
      analysis of covariance). Height SDS was: AI, -1.73 (0.12); GH, -1.43 (0.14);
      AI/GH, -1.25 (0.12) (P < .0012). Those treated through 36 months grew more.
      Regardless of treatment duration, height SDS at near-final height [n = 71; age,
      17.4 (0.2) years; bone age, 15.3 (0.1) years; height achieved, ~97.6%] was: AI, 
      1.4 (0.1); GH, -1.4 (0.2); AI/GH, -1.0 (0.1) (P = .06). Absolute height change
      was: AI, +18.2 (1.6) cm; GH, +20.6 (1.5) cm; AI/GH, +22.5 (1.4) cm (P = .01)
      (expected height gain at -2.0 height SDS, +13.0 cm). AI/GH had higher fat free
      mass accrual. Measures of bone health, safety labs, and adverse events were
      similar in all groups. Letrozole caused higher T and lower estradiol than
      anastrozole. CONCLUSIONS: Combination therapy with AI/GH increases height
      potential in pubertal boys with ISS more than GH and AI alone treated for 24-36
      months with a strong safety profile.

PMID- 27710264
TI  - Medical Teacher in Ten Minutes.

PMID- 27710265
TI  - Top-rated AMEE MedEdPublish Papers - August 2016.

PMID- 27710263
TI  - Mechanisms of Hyperbilirubinemia During Peginterferon Lambda-1a Therapy for
      Chronic Hepatitis C Infection: A Retrospective Investigation.
AB  - The phase 2b EMERGE study compared the efficacy/safety of peginterferon lambda-1a
      (Lambda) and peginterferon alfa-2a (Alfa), both with ribavirin (RBV), for
      treatment of chronic hepatitis C virus (HCV) infection. A key safety finding was
      a higher frequency of hyperbilirubinemia with Lambda/RBV versus Alfa/RBV. To
      characterize mechanisms of hyperbilirubinemia associated with Lambda/RBV, we
      conducted a retrospective analysis of safety data from the HCV genotype 1 and
      genotype 4 cohort of the EMERGE study. Subjects were randomized to once-weekly
      Lambda (120/180/240 MUg) or Alfa (180 MUg), with daily RBV, for 48 weeks. Early
      onset Lambda/RBV-related hyperbilirubinemia events (6-12 weeks) resulted mostly
      from RBV-induced hemolysis evidenced by sustained reticulocytosis and a
      predominantly unconjugated pattern of hyperbilirubinemia. The higher
      hyperbilirubinemia frequency with Lambda/RBV versus Alfa/RBV was attributed to
      bone marrow suppression known to occur with Alfa but not Lambda. Late-onset (>12
      weeks) Lambda/RBV-related hyperbilirubinemia events occurred most frequently with
      higher Lambda doses and were associated with increased levels of hepatic
      transaminase and direct bilirubin fractions compared with early events. This dual
      pattern of hyperbilirubinemia observed while on Lambda/RBV treatment is thought
      to be caused by exaggerated RBV-induced hemolysis in early-onset events compared
      with possible direct Lambda-induced hepatocellular toxicity in late-onset events.

PMID- 27710244
TI  - The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice
      Guideline.
AB  - OBJECTIVE: Lipodystrophy syndromes are extremely rare disorders of deficient body
      fat associated with potentially serious metabolic complications, including
      diabetes, hypertriglyceridemia, and steatohepatitis. Due to their rarity, most
      clinicians are not familiar with their diagnosis and management. This practice
      guideline summarizes the diagnosis and management of lipodystrophy syndromes not
      associated with HIV or injectable drugs. PARTICIPANTS: Seventeen participants
      were nominated by worldwide endocrine societies or selected by the committee as
      content experts. Funding was via an unrestricted educational grant from Astra
      Zeneca to the Pediatric Endocrine Society. Meetings were not open to the general
      public. EVIDENCE: A literature review was conducted by the committee.
      Recommendations of the committee were graded using the system of the American
      Heart Association. Expert opinion was used when published data were unavailable
      or scarce. CONSENSUS PROCESS: The guideline was drafted by committee members and
      reviewed, revised, and approved by the entire committee during group meetings.
      Contributing societies reviewed the document and provided approval. CONCLUSIONS:
      Lipodystrophy syndromes are heterogeneous and are diagnosed by clinical
      phenotype, supplemented by genetic testing in certain forms. Patients with most
      lipodystrophy syndromes should be screened for diabetes, dyslipidemia, and liver,
      kidney, and heart disease annually. Diet is essential for the management of
      metabolic complications of lipodystrophy. Metreleptin therapy is effective for
      metabolic complications in hypoleptinemic patients with generalized lipodystrophy
      and selected patients with partial lipodystrophy. Other treatments not specific
      for lipodystrophy may be helpful as well (eg, metformin for diabetes, and statins
      or fibrates for hyperlipidemia). Oral estrogens are contraindicated.

PMID- 27710313
TI  - Real-Time RT-PCR Assays for Detection and Genotyping of West Nile Virus Lineages
      Circulating in Africa.
AB  - West Nile virus (WNV) is an emerging arbovirus, circulating worldwide between
      birds and mosquitoes, which impacts human and animal health. Since the mid-1990s,
      WNV outbreaks have emerged in Europe and America and represent currently the
      primary cause of encephalitis in the United States. WNV exhibits a great genetic
      diversity with at least eight different lineages circulating in the world, and
      four (1, 2, Koutango, and putative new) are present in Africa. These different
      WNV lineages are not readily differentiated by serology, and thus, rapid
      molecular tools are required for diagnostic. We developed here real-time RT-PCR
      assays for detection and genotyping of African WNV lineages. The specificity of
      the assays was tested using other flaviviruses circulating in Africa. The
      sensitivity was determined by testing serial 10-fold dilutions of viruses and RNA
      standards. The assays provided good specificity and sensitivity and the
      analytical detection limit was 10 copies/reaction. The RT-PCR assays allowed the
      detection and genotyping of all WNV isolates in culture medium, human serum, and
      vertebrate tissues, as well as in field and experimental mosquito samples.
      Comparing the ratios of genome copy number/infectious virion (plaque-forming
      units), our study finally revealed new insight on the replication of these
      different WNV lineages in mosquito cells. Our RT-PCR assays are the first ones
      allowing the genotyping of all WNV African variants, and this may have important
      applications in surveillance and epidemiology in Africa and also for monitoring
      of their emergence in Europe and other continents.

PMID- 27710430
TI  - The isolation and functional identification on producing cellulase of Pseudomonas
      mendocina.
AB  - The straw can be degraded efficiently into humus by powerful enzymes from
      microorganisms, resulting in the accelerated circulation of N,P,K and other
      effective elements in ecological system. We isolated a strain through screening
      the straw degradation strains from natural humic straw in the low temperature
      area in northeast of china, which can produce cellulase efficiently. The strain
      was identified as Pseudomonas mendocina by using morphological, physiological,
      biochemical test, and molecular biological test, with the functional
      clarification on producing cellulase for Pseudomonas mendocina for the first
      time. The enzyme force constant Km and the maximum reaction rate (Vmax) of the
      strain were 0.3261 g/L and 0.1525 mg/(min.L) through the enzyme activity
      detection, and the molecular weight of the enzyme produced by the strain were
      42.4 kD and 20.4 kD based on SDS-PAGE. The effects of various ecological factors
      such as temperature, pH and nematodes on the enzyme produced by the strain in the
      micro ecosystem in plant roots were evaluated. The result showed that the optimum
      temperature was 28 degrees C, and the best pH was 7.4~7.8, the impact heavy metal
      was Pb2+ and the enzyme activity and biomass of Pseudomonas mendocina increased
      the movement and predation of nematodes.

PMID- 27710431
TI  - Comparative analysis of protective effects of curcumin, curcumin-beta
      cyclodextrin nanoparticle and nanoliposomal curcumin on unsymmetrical dimethyl
      hydrazine poisoning in mice.
AB  - The aim of this study was to compare the protective effects of curcumin, curcumin
      beta-cyclodextrin nanoparticle curcumin (BCD-CUR) and nanoliposomal curcumin
      (NLC) on unsymmetrical dimethylhydrazine (UDMH) induced poison in mice. Curcumin,
      BCD-CUR, and NLC were prepared and their properties of zeta potential, particle
      size, encapsulation efficiency, and loading capacity were characterized. Eighty
      eight male ICR mice on normal chow diet were randomly divided into 11 groups, and
      intraperitoneally injected with UDMH alone, or together with different doses of
      curcumin, BCD-CUR or NLC daily for up to 10 d. Enzyme activities of serum alanine
      transaminase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase
      (LDH) were analyzed by fully-automatic analyzer and neurotransmitter levels were
      determined with high performance liquid chromatography (HPLC). 150 mg/kg curcumin
      treatment alone significantly reduced levels of serum ALT and LDH that were
      induced by UDMH and markedly increased level of gamma-amino butyric acid (GABA)
      that were reduced by UDMH in the hippocampus. 150 mg/kg BCD-CUR not only
      decreased significantly the increase of ALT, LDH and glutamate (Glu) but also
      recovered levels of AST and GABA. 150 mg/kg NLC recovered profoundly levels of
      AST and GABA while decreased remarkably the UDMH induced increase of ALT, LDH,
      Glu and 5-hydroxytryptamine (5-HT). In addition, treatments with all tested doses
      of NLC significantly reduced the UMDH induced dopamine (DA), the monoamine
      neurotransmitter. NLC had more profound protective effects against liver and
      central nervous system injury induced by UDMH than a suspension of BCD-CUR or
      curcumin did in mice.

PMID- 27710432
TI  - Improvement in degradability of 58s glass scaffolds by ZnO and beta-TCP
      modification.
AB  - 58s bioactive glass shows great potential for bone defects repair. However, at
      early repairing stage, the degradation rate of 58s glass is too fast due to the
      fast ion-exchange. At later repairing stage, the degradation rate of 58s glass is
      too slow due to the high dense mineral layer. In this work, Zinc oxide (ZnO) and
      beta-tricalcium phosphate (beta-TCP) were introduced into 58s glass bone
      scaffolds to improve the degradability. The results showed that ZnO could
      decrease the degradation rate and promote the stability of 58s glass at early
      repairing stage. Moreover, the presence of beta-TCP appeared to increase the
      degradation rate at a later stage of repairing. Furthermore, in vitro
      biocompatibility study, carried out using human osteoblast-like cells (MG63),
      demonstrated that ZnO and beta-TCP enhanced cell attachment and proliferation.
      The study provided a reference for further research in bone tissue engineering.

PMID- 27710433
TI  - Explicit vascular reconstruction based on adjacent vector projection.
AB  - Blood vascular reconstruction plays an important role in vessel disease diagnosis
      and prognosis, treatment planning and surgery. Based on adjacent vector
      projection, a simple and robust explicit algorithm is presented for vascular
      reconstruction. It generates the base mesh and utilizes the Loop algorithm for
      perceptual refinement by mesh subdivision. In the end, the reconstructed vascular
      tree is rendered for volumetric visualization and localization of vascular
      malformations. Experimental results on the Aneurisk database have validated the
      capacity of the proposed algorithm in generating smooth surface and natural
      transition of high tortuosity in real time, while on clinical cases has verified
      its accuracy on pinning vascular stenosis.

PMID- 27710434
TI  - Preparation and properties of calcium citrate nanosheets for bone graft
      substitute.
AB  - A convenient and effective soft chemical method is presented for the synthesis of
      nano-scaled calcium citrate sheets. The preparation involved the precipitation of
      nano-calcium citrate by adding ethanol to reach the super saturation state of a
      solution containing calcium and citrate salts. The obtained nano-calcium citrate
      formed nanosheets, with the following dimensions: width of about 50~500 nm and
      thickness of about 8~30 nm. The results of the XRD analysis confirmed that the
      obtained sample is calcium citrate tetrahydrate, and the crystal degree decreased
      with an increase quantity of ethanol added. Animal experiments showed that the
      calcium citrate can promote the formation of new bone.

PMID- 27710435
TI  - Nanoindentation investigation of the stress exponent for the creep of dung beetle
      (Copris ochus Motschulsky) cuticle.
AB  - ABSTACT With the rapid development of bionic science, especially the progress
      that has been made in the fields of biomaterials and biomimetics, there is now
      great interest in the surface and internal mechanical properties of biological
      materials at the micro- and nanoscale. The study of micro- and nanoscale
      biomaterial mechanical properties could enable interdisciplinary applications in
      materials science, biological science and bionic science. Dung beetle (Copris
      ochus Motschulsky) cuticle is a viscoelastic material that is both viscous and
      flexible via elastic deformation under external forces; where stress sigma,
      strain epsilon and elastic modulus E are related in the following way: sigma =
      Eepsilon. In addition, as sigma is related to the rate of strain, time is also a
      factor. The stress-strain relationships of various parts of dung beetle cuticle
      were investigated in this paper. As time increased, the stress and strain of the
      material were found to decrease and increase, respectively, indicating that when
      the material was indented for a certain period, the interaction force between the
      indenter and the material gradually achieved a state of dynamic equilibrium.
      However, strain continued to occur until reaching a point of equilibrium because
      of the creep phenomenon. The stress-strain curves showed a strong character in
      each holding time condition: the longer the holding time, the more flattened the
      stress-strain curve. These findings will be useful in the advanced design of
      strong, lightweight, and biomimetic composites.

PMID- 27710436
TI  - Effects of Hydrolyzed Whey versus Other Whey Protein Supplements on the
      Physiological Response to 8 Weeks of Resistance Exercise in College-Aged Males.
AB  - OBJECTIVE: The objective of this study was to compare the chronic effects of
      different whey protein forms on body composition and performance when
      supplemented with resistance training. METHODS: Resistance-trained men (N = 56,
      21.4 +/- 0.4 years, 79.5 +/- 1.0 kg) participated in an 8-week resistance
      training regimen (2 upper-body sessions and 2 lower-body sessions per week) and
      received one of 4 double-blinded treatments: 30 g/serving carbohydrate placebo
      (PLA) or 30 g/serving protein from either (a) 80% whey protein concentrate (WPC),
      (b) high-lactoferrin-containing WPC (WPC-L), or (c) extensively hydrolyzed WPC
      (WPH). All subjects consumed 2 servings of treatment per day; specifically, once
      immediately before and after training and between meals on nontraining days.
      Blood collection, one repetition maximum (1RM) testing for bench press and hack
      squat, and body composition assessment using dual-energy x-ray absorptiometry
      (DXA) occurred prior to training and 48 hours following the last training
      session. RESULTS: Total body skeletal muscle mass increased in all groups (p <
      0.0125). There were similar between-group increases in upper-body (4%-7%,
      analysis of covariance [ANCOVA] interaction p = 0.73) and lower-body (24%-35%,
      ANCOVA interaction p = 0.85) 1RM strength following the intervention. Remarkably,
      WPH reduced fat mass (-6%), which was significantly different from PLA (+4.4%, p
      < 0.0125). No time or between-group differences were present for serum markers of
      health, metabolism, or muscle damage, with the exception of blood urea nitrogen
      being significantly lower for WPH than WPC (p < 0.05) following the intervention.
      CONCLUSIONS: WPH may augment fat loss but did not provide any other advantages
      when used in combination with resistance training. More mechanistic research is
      needed to examine how WPH affects adipose tissue physiology.

PMID- 27710437
TI  - Influence of football size on kicking performance in youth Australian rules
      footballers.
AB  - In Australian rules football structured increases in ball size during development
      end with the transition to the Size 5 (adult) ball at the Under-15 age group.
      This study assessed changes in kick technique and performance in experienced
      junior performers when using Size 4 and 5 Australian rules footballs.
      Participants (n = 22, 13.77 +/- 0.61 years) performed drop punt kicks in 2
      representative tasks; a Decision-Making Test (DMT) (n = 14) and Set-Shot Test
      (SST) (n = 14 + 8). Results indicate participants sustained their level of kick
      performance (accuracy and quality of ball spin) in both tests when using a Size 5
      football. Sustained kick performance in the DMT primarily resulted from
      adaptations to time-point technical measures at ball release. No significant
      differences were detected for technical measures between ball sizes in the SST. A
      dynamic kicking task (DMT) in combination with ball size manipulation may have
      placed greater demand on skill execution in comparison to a self-paced kicking
      task (SST). Results provide initial support for the utility of challenging
      representative dynamic and self-paced tasks, such as the DMT and SST used here
      for Australian football, for skill testing and practice in sport.

PMID- 27710596
TI  - The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women
      with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial.
AB  - OBJECTIVE: Previous studies have shown that the bioflavonoid quercetin has anti
      inflammatory and anti-nociceptive effects. We investigated the effect of
      quercetin supplementation on inflammation, disease severity, and clinical
      symptoms in women with rheumatoid arthritis (RA). METHODS: The present study was
      a randomized, double-blind, placebo-controlled clinical trial in which 50 women
      with RA were allocated into a quercetin (500 mg/day) or placebo group for 8
      weeks. Plasma levels of high-sensitivity tumor necrosis factor-alpha (hs
      TNFalpha), erythrocyte sedimentation rate (ESR), clinical symptoms including
      early morning stiffness (EMS), morning and after-activity pain, and tender (TSC)
      and swollen joint counts (SJC) were determined. Disease activity and functional
      disability were assessed by Disease Activity Score 28 (DAS-28), physician global
      assessment (PGA), and a health assessment questionnaire (HAQ) at the beginning
      and end of the study. RESULTS: Quercetin supplementation for 8 weeks
      significantly reduced EMS, morning pain, and after-activity pain (p < 0.05). DAS
      28 and HAQ scores decreased in the quercetin group compared to placebo and the
      number of patients with active disease significantly decreased in the quercetin
      group. Plasma hs-TNFalpha level was significantly reduced in the quercetin group
      compared to placebo (p < 0.05). There were no significant differences in TJC and
      SJC between groups but TJC significantly decreased in the quercetin group after
      the intervention. Supplementation had an effect on ESR but it was not significant
      (p > 0.05). CONCLUSIONS: Five hundred milligrams per day quercetin
      supplementation for 8 weeks resulted in significant improvements in clinical
      symptoms, disease activity, hs-TNFalpha, and HAQ in women with RA.

PMID- 27710645
TI  - Perceptions of national recruitment for orthodontic specialty registrars: 2012
      2014.
AB  - AIM: To assess the changes in interviewees' and interviewers' perceptions and
      experiences of national recruitment and a multi-station interview (MSI) for the
      selection of Orthodontic Specialty Registrars to UK training programmes from 2012
      to 2014. DESIGN: Questionnaire-based longitudinal survey. SETTING: Interviews for
      selection of Orthodontic Specialty Registrars (StRs) held at London Deanery,
      London, UK. METHODS: Interviewees and interviewers completed an anonymous
      questionnaire comprising of 17 and 26 questions, respectively. RESULTS:
      Interviewees: The number, age (p = 0.29) and time since qualification (p = 0.90)
      increased slightly over the 3 years but these changes were not statistically
      significant. The proportion of females (p = 0.32) and those with a UK primary
      dental qualification (p = 0.52) varied slightly but the variation was not
      statistically significant. The proportion that had experience of the MSI format
      increased significantly over the 3 years (p < 0.01). More than 75% were positive
      about the organization, experience and fairness of the MSI interview format.
      Interviewers: The age (p = 0.54), time since being a consultant (p = 0.90),
      proportion of females (p = 0.43) and those favouring the MSI format (p = 0.29)
      varied slightly but this was not statistically significant. More than 75% were
      positive about the organization, experience and fairness of the MSI format. More
      than 90% of interviewers thought that the process selected the best candidates,
      was fair and that more than one assessor was required at each station.
      CONCLUSIONS: Interviewees were consistently very positive about the organization
      and fairness of the MSI format. Interviewers were consistently very positive
      about the selection of candidates, fairness and conduct of the MSIs.

PMID- 27710646
TI  - Stabilizing Cr species in incinerator fly ashes with/without kaolin addition
      through a firing process: a molecular study on heated Cr.
AB  - Cr speciation in Cr-sorbing washed incinerator fly ash (IFA) after heating up to
      1100 degrees C is temperature dependent. Higher temperature leads to a greater
      level of chemical reduction of Cr(VI) that is considerably more toxic than
      Cr(III). Most Cr(VI) sorbed washed IFA is effectively transformed into Cr(III)
      after heating to 1100 degrees C for 2 h, as indicated by the disappearance of
      hexavalent pre-edge peak of Cr K-edge X-ray absorption near edge structure
      (XANES) spectrum. After heating the Cr-sorbing IFA to 100 degrees C and 500
      degrees C for 2 h, water-soluble CaCrO4 is determined to be the principal Cr
      species due to the chemical reaction between the sorbed Cr(VI) and CaO components
      of washed fly ash, based on the comparison between sample and reference XANES
      spectra. Replacing half of the washed fly ash with kaolin could effectively
      reduce all Cr(VI) after heating to ? 900 degrees C for 2 h.

PMID- 27710701
TI  - The Consumption of Breakfast, Fish and/or Caffeine does not Predict Study
      Progress in Adult Distance Education.
AB  - Consumption of breakfast, fish, or caffeine are each separately often
      investigated in relation to learning performance in traditional education, but
      not in distance education (DE). The objective of this study was to investigate
      whether the relations between the consumption of breakfast, fish, and/or caffeine
      on the one hand and learning performance on the other are also found in DE
      students. This population is different from traditional students and
      characterized by a different profile in terms of age, personal and work
      responsibilities as well as other demographics. In an observational longitudinal
      study, the consumption of breakfast, fish, and caffeine of 1157 DE students (18
      76 years old, mean 35.8+/-11.1 years) was used to predict learning performance
      using multiple regression analysis. In an online digital survey, university
      students provided information about their consumption of these nutritional
      measures and on important covariates. Learning performance, measured as study
      progress (i.e., the number of successfully completed modules), was evaluated
      objectively after 14 months. Results showed that adding the consumption of
      breakfast, fish, and caffeine to the covariate model did not fit the data better,
      chi2 (3, N = 1155) = 3.287, p = 0.35. This means that neither the consumption of
      breakfast nor fish nor caffeine predicted study progress in adults participating
      in DE. This study is important as it is the first to report on these relations in
      this specific age group and educational setting, which is increasingly important
      due to the increased preference for this type of education.

PMID- 27710700
TI  - Long-term effects of back extensor strengthening exercises on quality of life in
      women with osteoporosis.
AB  - The aim of the present study was to evaluate the long-term effect of back
      extensor strengthening exercises on health-related quality of life (QOL) in women
      with osteoporosis. In this randomized clinical trial, 183 women with osteoporosis
      were treated with pharmacotherapy and weight-bearing and balance-training
      exercises. The case group additionally performed back extensor exercises at home.
      Patients filled out the Persian version of the Short Form (SF-36) QOL
      questionnaire at baseline and 6 months post treatment. At the end, all physical
      and mental parameters of the SF-36 questionnaire improved significantly in the
      case group, except for one subscale of mental health, compared to the control
      group. In the control group, only some physical health dimensions (bodily pain,
      role limitation, physical function, vitality), and mental health status as a
      mental health subscale improved. In conclusion, considering a major impact of
      back extensor exercises on improving QOL in women with osteoporosis over the long
      term, these exercises should be prescribed in routine management of these
      patients.

PMID- 27710704
TI  - Effect of Radiofrequency Radiation on Human Hematopoietic Stem Cells.
AB  - Exposure to electromagnetic fields in the radiofrequency range is ubiquitous,
      mainly due to the worldwide use of mobile communication devices. With improving
      technologies and affordability, the number of cell phone subscriptions continues
      to increase. Therefore, the potential effect on biological systems at low
      intensity radiation levels is of great interest. While a number of studies have
      been performed to investigate this issue, there has been no consensus reached
      based on the results. The goal of this study was to elucidate the extent to which
      cells of the hematopoietic system, particularly human hematopoietic stem cells
      (HSC), were affected by mobile phone radiation. We irradiated HSC and HL-60 cells
      at frequencies used in the major technologies, GSM (900 MHz), UMTS (1,950 MHz)
      and LTE (2,535 MHz) for a short period (4 h) and a long period (20 h/66 h), and
      with five different intensities ranging from 0 to 4 W/kg specific absorption rate
      (SAR). Studied end points included apoptosis, oxidative stress, cell cycle, DNA
      damage and DNA repair. In all but one of these end points, we detected no clear
      effect of mobile phone radiation; the only alteration was found when quantifying
      DNA damage. Exposure of HSC to the GSM modulation for 4 h caused a small but
      statistically significant decrease in DNA damage compared to sham exposure. To
      our knowledge, this is the first published study in which putative effects (e.g.,
      genotoxicity or influence on apoptosis rate) of radiofrequency radiation were
      investigated in HSC. Radiofrequency electromagnetic fields did not affect cells
      of the hematopoietic system, in particular HSC, under the given experimental
      conditions.

PMID- 27710702
TI  - State-of-the-Art Advances in Radiation Biodosimetry for Mass Casualty Events
      Involving Radiation Exposure.
AB  - With the possibility of large-scale terrorist attacks around the world, the need
      for modeling and development of new medical countermeasures for potential future
      chemical, biological, radiological and nuclear (CBRN) has been well established.
      Project Bioshield, initiated in 2004, provided a framework to develop and
      expedite research in the field of CBRN exposures. To respond to large-scale
      population exposures from a nuclear event or radiation dispersal device (RDD),
      new methods for determining received dose using biological modeling became
      necessary. The field of biodosimetry has advanced significantly beyond this
      original initiative, with expansion into the fields of genomics, proteomics,
      metabolomics and transcriptomics. Studies are ongoing to evaluate the use of
      lymphocyte kinetics for dose assessment, as well as the development of field
      deployable EPR technology. In addition, expansion of traditional cytogenetic
      assessment methods through the use of automated platforms and the development of
      laboratory surge capacity networks have helped to advance our biodefense
      preparedness. In this review of the latest advances in the field of biodosimetry
      we evaluate our progress and identify areas that still need to be addressed to
      achieve true field-deployment readiness.

PMID- 27710703
TI  - Total-Body Irradiation Exacerbates Dissemination of Cutaneous Candida Albicans
      Infection.
AB  - Exposure to radiation, particularly a large or total-body dose, weakens the
      immune system through loss of bone marrow precursor cells, as well as diminished
      populations of circulating and tissue-resident immune cells. One such population
      is the skin-resident immune cells. Changes in the skin environment can be of
      particular importance as the skin is also host to a number of commensal
      organisms, including Candida albicans , a species of fungus that causes
      opportunistic infections in immunocompromised patients. In a previous study, we
      found that a 6 Gy sublethal dose of radiation in mice caused a reduction of
      cutaneous dendritic cells, indicating that the skin may have a poorer response to
      infection after irradiation. In this study, the same 6 Gy sublethal radiation
      dose led to a weakened response to a C. ablicans cutaneous infection, which
      resulted in systemic dissemination from the ear skin to the kidneys. However,
      this impaired response was mitigated through the use of interleukin-12 (IL-12)
      administered to the skin after irradiation. Concomitantly with this loss of local
      control of infection, we also observed a reduction of CD4+ and CD8+ T cells in
      the skin, as well as the reduced expression of IFN-gamma, CXCL9 and IL-9, which
      influence T-cell infiltration and function in infected skin. These changes
      suggest a mechanism by which an impaired immune environment in the skin after a
      sublethal dose of radiation increases susceptibility to an opportunistic fungal
      infection. Thus, in the event of radiation exposure, it is important to include
      antifungal agents, or possibly IL-12, in the treatment regimen, particularly if
      wounds are involved that result in loss of the skin's physical barrier function.

PMID- 27710705
TI  - Pomegranate peel extract attenuates oxidative stress by decreasing coronary
      angiotensin-converting enzyme (ACE) activity in hypertensive female rats.
AB  - Based on the antioxidant properties of pomegranate, this study was designed to
      investigate the effects of pomegranate peel extract on damage associated with
      hypertension and aging in a spontaneously hypertensive rat (SHR) model. The
      influence of pomegranate consumption was examined on systolic blood pressure
      (SBP), angiotensin-converting enzyme (ACE) coronary activity, oxidative stress,
      and vascular morphology. Four- or 28-wk-old SHR model rats were treated for 30 d,
      with terminal experimental animal age being 8 and 32 wk, respectively, with
      either pomegranate extract (SHR-PG) or filtered water (SHR). Data showed
      significant reduction in SBP and coronary ACE activity in both age groups. The
      levels of superoxide anion, a measure of oxidative stress, were significantly
      lower in animals in the SHR-PG group compared to SHR alone. Coronary morphology
      demonstrated total increases in vascular wall areas were in the SHR group, and
      pomegranate peel extract diminished this effect. Pomegranate peel extract
      consumption conferred protection against hypertension in the SHR model. This
      finding was demonstrated by marked reduction in coronary ACE activity, oxidative
      stress, and vascular remodelling. In addition, treatment was able to reduce SBP
      in both groups. Evidence indicates that the use of pomegranate peel extract may
      prove beneficial in alleviating coronary heart disease.

PMID- 27710762
TI  - The Effects of Cannabis on Inpatient Agitation, Aggression, and Length of Stay.
AB  - OBJECTIVE: This study examines the association between cannabis use and the
      hospital course of patients admitted to the psychiatric inpatient unit with a
      diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder. Many
      confounding variables potentially contribute to the clinical presentation of
      hospitalized patients in the psychiatric unit. Illicit drug use, in particular,
      has been associated with acute agitation, and questions can be raised as to what
      lasting effects drug use prior to admission may have throughout a patient's
      hospital stay. METHODS: Subjects with a discharge diagnosis of bipolar disorder,
      schizophrenia, schizoaffective disorder, or psychosis not otherwise specified (N
      = 201) were retrospectively identified, and those with positive results of urine
      drug screen for cannabis on admission were compared to negative counterparts.
      Agitation and aggression were measured using an adaptation of the Excited
      Component of the Positive and Negative Syndrome Scale (PANSS-EC). These markers
      were also quantified by comparing charted episodes of restraint and seclusion and
      administration of as needed medications, such as benzodiazepines and
      antipsychotics. RESULTS: Positive urine drug screen results for cannabis was
      correlated with young (p = .001) males (p = .003) with bipolar disorder (p =
      .009) exhibiting active manic symptoms (p = .003) at the time of admission.
      Cannabis use was further associated with a shorter length of stay (p = .008),
      agitation triggering adapted PANSS-EC nursing assessments (p = .029), and oral
      medications as needed (p = .002) for agitation. CONCLUSIONS: Cannabis use, as
      defined by positive urine drug screen results, was more common in patients with
      bipolar disorder and was accompanied by a higher incidence of inpatient
      agitation. Although these patients also had short hospital lengths of stay, there
      was no clear relationship between level of agitation and length of stay across
      all patient groups. One possible explanation for patients with bipolar disorder
      experiencing short lengths of stay is that their source of agitation may be more
      closely related to a complex effect of cannabis use rather than a sole etiology
      of mental illness. Inpatient clinicians should be aware of patient cannabis use
      proximate to admission.

PMID- 27710763
TI  - Disparities in Who Receives Weight-Loss Advice From a Health Care Provider: Does
      Income Make a Difference?
AB  - INTRODUCTION: The US Preventive Services Task Force recommends that all patients
      be screened for obesity and, if needed, be provided weight-loss advice. However,
      the prevalence of such advice is low and varies by patient demographics. This
      study aimed to describe the determinants of receiving weight-loss advice among a
      sample with a high proportion of low-income, racial/ethnic minority individuals.
      METHODS: Data were collected from a telephone survey of 1,708 households in 2009
      and 2010 in 5 cities in New Jersey. Analyses were limited to 1,109 overweight or
      obese adults. Multivariate logistic regression determined the association of
      participants' characteristics with receiving weight-loss advice from their health
      care provider. Two models were used to determine differences by income and
      insurance status. RESULTS: Of all overweight or obese respondents, 35% reported
      receiving advice to lose weight. Receiving advice was significantly associated
      with income in multivariate analysis. Compared with those with an income at or
      below 100% of the federal poverty level (FPL), those within 200% to 399% of the
      FPL had 1.60 higher odds of receiving advice (P = .02), and those with an income
      of 400% or more of the FPL had 1.73 higher odds of receiving advice (P = .03).
      The strength of the association did not change after adjusting for health
      insurance. CONCLUSION: Income is a significant predictor of whether or not
      overweight or obese adults receive weight-loss advice after adjustment for
      demographic variables, health status, and insurance status. Further work is
      needed to examine why disparities exist in who receives weight-loss advice.
      Health care providers should provide weight-loss advice to all patients,
      regardless of income.

PMID- 27710764
TI  - Absenteeism and Employer Costs Associated With Chronic Diseases and Health Risk
      Factors in the US Workforce.
AB  - INTRODUCTION: Employers may incur costs related to absenteeism among employees
      who have chronic diseases or unhealthy behaviors. We examined the association
      between employee absenteeism and 5 conditions: 3 risk factors (smoking, physical
      inactivity, and obesity) and 2 chronic diseases (hypertension and diabetes).
      METHODS: We identified 5 chronic diseases or risk factors from 2 data sources:
      MarketScan Health Risk Assessment and the Medical Expenditure Panel Survey
      (MEPS). Absenteeism was measured as the number of workdays missed because of
      sickness or injury. We used zero-inflated Poisson regression to estimate excess
      absenteeism as the difference in the number of days missed from work by those who
      reported having a risk factor or chronic disease and those who did not.
      Covariates included demographics (eg, age, education, sex) and employment
      variables (eg, industry, union membership). We quantified absenteeism costs in
      2011 and adjusted them to reflect growth in employment costs to 2015 dollars.
      Finally, we estimated absenteeism costs for a hypothetical small employer (100
      employees) and a hypothetical large employer (1,000 employees). RESULTS:
      Absenteeism estimates ranged from 1 to 2 days per individual per year depending
      on the risk factor or chronic disease. Except for the physical inactivity and
      obesity estimates, disease- and risk-factor-specific estimates were similar in
      MEPS and MarketScan. Absenteeism increased with the number of risk factors or
      diseases reported. Nationally, each risk factor or disease was associated with
      annual absenteeism costs greater than $2 billion. Absenteeism costs ranged from
      $16 to $81 (small employer) and $17 to $286 (large employer) per employee per
      year. CONCLUSION: Absenteeism costs associated with chronic diseases and health
      risk factors can be substantial. Employers may incur these costs through lower
      productivity, and employees could incur costs through lower wages.

PMID- 27710765
TI  - Divergent Perceptions of Barriers to Diabetic Retinopathy Screening Among
      Patients and Care Providers, Los Angeles, California, 2014-2015.
AB  - INTRODUCTION: Despite availability of screening for diabetic retinopathy, testing
      is underused by many low-income and racial/ethnic minority patients with
      diabetes. We examined perceived barriers to diabetic retinopathy screening among
      low-income patients and their health care providers and provider staffers.
      METHODS: We collected survey data from 101 patients with diabetes and 44
      providers and staffers at a safety-net clinic where annual diabetic retinopathy
      screening rates were low. Barriers specified in the survey were derived from the
      literature. RESULTS: Patients surveyed (mean [standard deviation] age, 54.0 [7.7]
      y; 41% were male) were primarily Hispanics (70%) and African Americans (27%) of
      low socioeconomic status. Overall, 55% of patients received diabetic retinopathy
      screening in the previous year. Patients who could not explain why this screening
      is needed reported more barriers than patients who could (2.5 vs 1.4 barriers, P
      = .02). Fewer patients reported that they experienced barriers such as
      transportation (15%), language issues (15%), cultural beliefs or myths (4%),
      denial (8%), and fear (5%), which providers and staffers considered very or
      extremely important (all P < .001). Financial burdens (26%) and depression (22%)
      were most commonly reported by patients as barriers, yet providers and staffers
      did not rate these barriers as important, P < .001. CONCLUSION: Patients and
      health care providers had markedly divergent perceptions of barriers to diabetic
      retinopathy screening. Patients with poor understanding of the need for screening
      were more likely to report such barriers. These results suggest a need for active
      community engagement to find key elements for education programs and other
      interventions to increase rates of diabetic retinopathy screening, particularly
      among low-income, minority populations.

PMID- 27710766
TI  - An event map of memory space in the hippocampus.
AB  - The hippocampus has long been implicated in both episodic and spatial memory,
      however these mnemonic functions have been traditionally investigated in separate
      research strands. Theoretical accounts and rodent data suggest a common mechanism
      for spatial and episodic memory in the hippocampus by providing an abstract and
      flexible representation of the external world. Here, we monitor the de novo
      formation of such a representation of space and time in humans using fMRI. After
      learning spatio-temporal trajectories in a large-scale virtual city, subject
      specific neural similarity in the hippocampus scaled with the remembered
      proximity of events in space and time. Crucially, the structure of the entire
      spatio-temporal network was reflected in neural patterns. Our results provide
      evidence for a common coding mechanism underlying spatial and temporal aspects of
      episodic memory in the hippocampus and shed new light on its role in interleaving
      multiple episodes in a neural event map of memory space.

PMID- 27710767
TI  - Unique membrane properties and enhanced signal processing in human neocortical
      neurons.
AB  - The advanced cognitive capabilities of the human brain are often attributed to
      our recently evolved neocortex. However, it is not known whether the basic
      building blocks of the human neocortex, the pyramidal neurons, possess unique
      biophysical properties that might impact on cortical computations. Here we show
      that layer 2/3 pyramidal neurons from human temporal cortex (HL2/3 PCs) have a
      specific membrane capacitance (Cm) of ~0.5 uF/cm2, half of the commonly accepted
      'universal' value (~1 uF/cm2) for biological membranes. This finding was
      predicted by fitting in vitro voltage transients to theoretical transients then
      validated by direct measurement of Cm in nucleated patch experiments. Models of
      3D reconstructed HL2/3 PCs demonstrated that such low Cm value significantly
      enhances both synaptic charge-transfer from dendrites to soma and spike
      propagation along the axon. This is the first demonstration that human cortical
      neurons have distinctive membrane properties, suggesting important implications
      for signal processing in human neocortex.

PMID- 27710768
TI  - Active suppression of a leaf meristem orchestrates determinate leaf growth.
AB  - Leaves are flat determinate organs derived from indeterminate shoot apical
      meristems. The presence of a specific leaf meristem is debated, as anatomical
      features typical of meristems are not present in leaves. Here we demonstrate that
      multiple NGATHA (NGA) and CINCINNATA-class-TCP (CIN-TCP) transcription factors
      act redundantly, shortly after leaf initiation, to gradually restrict the
      activity of a leaf meristem in Arabidopsis thaliana to marginal and basal
      domains, and that their absence confers persistent marginal growth to leaves,
      cotyledons and floral organs. Following primordia initiation, the restriction of
      the broadly acting leaf meristem to the margins is mediated by the juxtaposition
      of adaxial and abaxial domains and maintained by WOX homeobox transcription
      factors, whereas other marginal elaboration genes are dispensable for its
      maintenance. This genetic framework parallels the morphogenetic program of shoot
      apical meristems and may represent a relic of an ancestral shoot system from
      which seed plant leaves evolved.

PMID- 27710769
TI  - The isolated voltage sensing domain of the Shaker potassium channel forms a
      voltage-gated cation channel.
AB  - Domains in macromolecular complexes are often considered structurally and
      functionally conserved while energetically coupled to each other. In the modular
      voltage-gated ion channels the central ion-conducting pore is surrounded by four
      voltage sensing domains (VSDs). Here, the energetic coupling is mediated by
      interactions between the S4-S5 linker, covalently linking the domains, and the
      proximal C-terminus. In order to characterize the intrinsic gating of the voltage
      sensing domain in the absence of the pore domain, the Shaker Kv channel was
      truncated after the fourth transmembrane helix S4 (Shaker-iVSD). Shaker-iVSD
      showed significantly altered gating kinetics and formed a cation-selective ion
      channel with a strong preference for protons. Ion conduction in Shaker-iVSD
      developed despite identical primary sequence, indicating an allosteric influence
      of the pore domain. Shaker-iVSD also displays pronounced 'relaxation'. Closing of
      the pore correlates with entry into relaxation suggesting that the two processes
      are energetically related.

PMID- 27710771
TI  - Modelling the impact of water activity and fat content of dry-cured ham on the
      reduction of Salmonella enterica by high pressure processing.
AB  - This work aimed to quantify the impact of aw and fat content of dry-cured ham on
      the Log reduction of Salmonella enterica by high pressure (HP). Dry-cured ham
      with adjusted aw (0.86-0.96) and fat content (10-50%) was inoculated with S.
      enterica and pressurised (347-852MPa, 5min/15 degrees C), following a Central
      Composite Design. Polynomial regression indicated a significant impact of
      pressure and aw on S. enterica HP-lethality. By lowering aw a clear
      piezoprotection was observed. At low aw (0.88) the S. enterica reduction was
      little affected by increasing pressure (e.g. 2.3 to 3.2 Logs at 450 to 750MPa,
      respectively). At the highest aw the estimated inactivation ranged from 3.3 to
      8.9 Logs at 450 to 750MPa, respectively. No significant piezoprotective effect on
      S. enterica was recorded by the fat content. The relevance of food
      characteristics on the HP-lethality of S. enterica indicate the need to validate
      the HP effectiveness on the specific product.

PMID- 27710772
TI  - Impact of high oxygen and vacuum retail ready packaging formats on lamb loin and
      topside eating quality.
AB  - Lamb steaks from semimembranosus (SM) and longissimus thoracis et lumborum (LTL)
      muscles were allocated to three different packaging treatments - Darfresh(r)
      vacuum skin packaging (VSP), Darfresh(r) Bloom packaging (80% O2:20% CO2; Hi-Ox
      DB) or high oxygen modified atmosphere packaging (80% O2:20% CO2; Hi-Ox-MAP) -
      and stored in simulated retail display for 5 or 10days and then subjected to
      consumer sensory and chemical analyses. Hi-Ox-MAP and Hi-Ox-DB samples had lower
      tenderness, flavor, juiciness and overall liking scores and higher TBARS values,
      compared to VSP. Hi-Ox-MAP samples deteriorated in juiciness and flavor between 5
      and 10days. Hi-Ox-MAP LTL samples had a lower myofibrillar fragmentation index,
      consistent with reduced proteolysis, although desmin proteolysis and desmin and
      troponin-T cross-linking were not influenced by packaging. The LTL exhibited
      greater desmin degradation and reduced desmin cross-linking relative to the SM,
      supporting the higher tenderness scores in this muscle. Direct packaging of lamb
      into retail ready VSP may provide the sheepmeat industry with greater flexibility
      while increasing consumer satisfaction.

PMID- 27710770
TI  - Atomic mutagenesis in ion channels with engineered stoichiometry.
AB  - C-type inactivation of potassium channels fine-tunes the electrical signaling in
      excitable cells through an internal timing mechanism that is mediated by a
      hydrogen bond network in the channels' selectively filter. Previously, we used
      nonsense suppression to highlight the role of the conserved Trp434-Asp447 indole
      hydrogen bond in Shaker potassium channels with a non-hydrogen bonding homologue
      of tryptophan, Ind (Pless et al., 2013). Here, molecular dynamics simulations
      indicate that the Trp434Ind hydrogen bonding partner, Asp447, unexpectedly 'flips
      out' towards the extracellular environment, allowing water to penetrate the space
      behind the selectivity filter while simultaneously reducing the local negative
      electrostatic charge. Additionally, a protein engineering approach is presented
      whereby split intein sequences are flanked by endoplasmic reticulum
      retention/retrieval motifs (ERret) are incorporated into the N- or C- termini of
      Shaker monomers or within sodium channels two-domain fragments. This system
      enabled stoichiometric control of Shaker monomers and the encoding of multiple
      amino acids within a channel tetramer.

PMID- 27710773
TI  - Bioactive peptides in beef: Endogenous generation through postmortem aging.
AB  - The present research was performed to investigate endogenous release of bioactive
      peptides in beef during postmortem aging times (1, 10 and 20days). Gradually
      decreased Warner-Bratzler shear force (WBSF) values of longissimus thoracis (LT)
      and semitendinosus (ST) muscles were observed and the degradation of structural
      proteins and collagen led to release of low-molecular weight (<3kDa) peptides.
      These peptides exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging
      capacity, ACE- and renin-inhibitory activities. The peptide sequences were
      identified by liquid chromatography-electrospray ionization-mass spectrometry (LC
      ESI-MS). In silico analysis (PeptideRanker and BIOPEP) of their bioactivity
      potentials demonstrated peptides with the predicted bioactivity scores (>0.8) as
      well as collagen peptides with bioactivity scores (0.6-0.8). The present findings
      provide insights on development of healthy beef through postmortem aging at 4
      degrees C.

PMID- 27710774
TI  - The release of dormancy, a wake-up call for seeds to germinate.
AB  - Seed dormancy determines the timing of germination, thereby contributing to
      successful seedling establishment and plant fitness. The induction and release of
      dormancy are controlled by various regulators like plant hormones and dormancy
      proteins. The relative strengths of these regulators are influenced by
      environmental factors during seed maturation and storage. In the last few years
      additional processes have been identified to be involved in the release of
      dormancy during seed storage with an important role for non-enzymatic oxidative
      reactions. However, the relations between the different dormancy regulators are
      not fully understood yet. Finally, all accumulated information will be processed
      in the seed during early seed imbibition and lead to the decision to germinate or
      not.

PMID- 27710775
TI  - Evaluation of the impacts of cooperative adaptive cruise control on reducing rear
      end collision risks on freeways.
AB  - Although plenty of studies have been conducted recently about the impacts of
      cooperative adaptive cruise control (CACC) system on traffic efficiency, there
      are few researches analyzing the safety effects of this advanced driving
      assistant system. Thus, the primary objective of this study is to evaluate the
      impacts of the CACC system on reducing rear-end collision risks on freeways. The
      CACC model is firstly developed, which is based on the Intelligent Driver Model
      (IDM). Then, two surrogated safety measures, derived from the time-to-collision
      (TTC), denoting time exposed time-to-collision (TET) and time integrated time-to
      collision (TIT), are introduced for quantifying the collision risks. And the
      safety effects are analyzed both theoretically and experimentally, by the linear
      stability analysis and simulations. The theoretical and simulation results
      conformably indicate that the CACC system brings dramatic benefits for reducing
      rear-end collision risks (TET and TIT are reduced more than 90%, respectively),
      when the desired time headway and time delay are set properly. The sensitivity
      analysis indicates there are few differences among different values of the
      threshold of TTC and the length of a CACC platoon. The results also show that the
      safety improvements weaken with the decrease of the penetration rates of CACC on
      the market and the increase of time delay between platoons. We also evaluate the
      traffic efficiency of the CACC system with different desired time headway.

PMID- 27710776
TI  - Buffering the effects of peer victimization on adolescent non-suicidal self
      injury: The role of self-compassion and family cohesion.
AB  - Non-suicidal self-injury (NSSI) is a significant behavioral problem among
      adolescents all over the world. This study examined the longitudinal relationship
      between peer victimization and NSSI, as well as the buffering effects of self
      compassion and family cohesion on this relationship. Data were collected at two
      time points from 525 secondary school students (226 girls; Mage = 12.97, SD =
      1.02) in China. Results showed that peer victimization (marginally) significantly
      predicted NSSI over time even after controlling for Wave 1 NSSI. This association
      was weakened under the condition of high levels of self-compassion. Findings of
      this study emphasize the buffering effect of self-compassion in the relationship
      between peer victimization and NSSI, and are informative for prevention and
      intervention of this behavioral problem.

PMID- 27710777
TI  - Early ultrastructural events of skeletal muscle damage following cardiotoxin
      induced injury and glycerol-induced injury.
AB  - In this study, we investigated the early changes of skeletal muscle damage in
      response to injuries induced by cardiotoxin (CTX) and glycerol by using both
      light microscopy and transmission electron microscopy. Normal, non-dystrophic,
      adult male mice were used in this study. Tibialis anterior (TA) muscles were
      injected either with CTX or glycerol. Samples were collected at intervals
      starting from 1h up to 4days after injury. Injured muscles were subjected to both
      histological and ultrastructural analyses. CTX-induced injury caused
      mitochondrial accumulation and swelling followed by lysis, while glycerol-induced
      injury caused accumulation of vesicles with focal disruption of the basal lamina,
      indicating that the injuries have different mechanisms of damage to myofibers.
      Moreover, inflammatory cells, including neutrophils and macrophages, were
      recruited earlier and in larger numbers after CTX-induced injury than after
      glycerol-induced injury. On the other hand, satellite cells (SCs) activation
      started at 6h after both injuries, as indicated by an increase in both the length
      and cytoplasmic-to-nuclear ratio. However, there were significantly longer SCs
      with a higher cytoplasmic-to-nuclear ratio in the CTX-injured muscles than in the
      glycerol-injured muscles at day 4. In conclusion, our results demonstrated a
      difference between CTX and glycerol in their damage to myofibers; CTX damages
      myofiber mitochondria, while glycerol damages the myofiber cell membrane and
      alters osmosis. In addition, CTX-induced injury caused earlier and more extensive
      inflammatory infiltration than did glycerol-induced injury. This study is the
      first study to shed light on the early events following skeletal muscle injury
      induced by CTX and glycerol.

PMID- 27710779
TI  - Probabilistic representation in syllogistic reasoning: A theory to integrate
      mental models and heuristics.
AB  - This paper presents a new theory of syllogistic reasoning. The proposed model
      assumes there are probabilistic representations of given signature situations.
      Instead of conducting an exhaustive search, the model constructs an individual
      based "logical" mental representation that expresses the most probable state of
      affairs, and derives a necessary conclusion that is not inconsistent with the
      model using heuristics based on informativeness. The model is a unification of
      previous influential models. Its descriptive validity has been evaluated against
      existing empirical data and two new experiments, and by qualitative analyses
      based on previous empirical findings, all of which supported the theory. The
      model's behavior is also consistent with findings in other areas, including
      working memory capacity. The results indicate that people assume the
      probabilities of all target events mentioned in a syllogism to be almost equal,
      which suggests links between syllogistic reasoning and other areas of cognition.

PMID- 27710780
TI  - Diminishing seasonality of self-harm: Temporal trends in Hong Kong SAR.
AB  - BACKGROUND: The study of temporal variation in self-harm is important to
      understanding the underlying mechanisms of its occurrence. There are fewer
      studies on temporal variation in self-harm than in suicide. The aim of this study
      was to examine the seasonality of self-harm in Hong Kong and to test the
      hypothesis of diminishing seasonality. METHODS: We used secondary data from
      medical records of self-harm obtained from all the public hospitals in Hong Kong
      under the management of the Hospital Authority. We identified 59,473 distinct
      episodes involving 36,411 patients. From these, monthly statistics of self-harm
      from January 2002 to December 2011 were calculated. Harmonic analysis was
      conducted to examine the presence and magnitude of seasonality. RESULTS: A bi
      seasonal pattern alongside a stronger one-cycle pattern from 2002 to 2006 was
      identified. During the period 1997-2001, this contracted to a one-cycle pattern
      with a peak in summer (May to July) and a nadir in winter (December). The
      magnitude of seasonality diminished greatly, as shown by harmonic analysis. The
      extent of diminishing seasonality was larger among women and people under 55
      years old. LIMITATIONS: The study covered only self-harm patients who had visited
      a hospital. Cases which required no medical attention and those where the patient
      consulted private doctors could not be included, indicating bias towards more
      severe cases of injury and poisoning. CONCLUSION: This study provides some
      evidence of diminishing and even vanishing seasonality of self-harm in Hong Kong,
      a phenomenon mainly found in younger individuals. It could be related to the
      increasing use of social media to connect people, especially the younger
      generation. The impact of seasonal events and activities, as in the past, has
      become less significant in the social media era.

PMID- 27710778
TI  - Slow wave sleep and accelerated forgetting.
AB  - We investigated whether the benefit of slow wave sleep (SWS) for memory
      consolidation typically observed in healthy individuals is disrupted in people
      with accelerated long-term forgetting (ALF) due to epilepsy. SWS is thought to
      play an active role in declarative memory in healthy individuals and,
      furthermore, electrographic epileptiform activity is often more prevalent during
      SWS than during wakefulness or other sleep stages. We studied the relationship
      between SWS and the benefit of sleep for memory retention using a word-pair
      associates task. In both the ALF and the healthy control groups, sleep conferred
      a memory benefit. However, the relationship between the amount of SWS and sleep
      related memory benefits differed significantly between the groups. In healthy
      participants, the amount of SWS correlated positively with sleep-related memory
      benefits. In stark contrast, the more SWS, the smaller the sleep-related memory
      benefit in the ALF group. Therefore, contrary to its role in healthy people, SWS
      associated brain activity appears to be deleterious for memory in patients with
      ALF.

PMID- 27710782
TI  - Are You Smarter Than a Teenager? Maybe Not When It Comes to Reinforcement
      Learning.
AB  - Adolescence is a time of tumultuous behavior that may result, in part, from brain
      circuitry that enhances reward seeking. In this issue of Neuron, Davidow et al.
      (2016) present a convincing argument that adolescent brain functionality can be
      adaptive in certain contexts, particularly probabilistic learning environments.

PMID- 27710781
TI  - Percutaneous mitral valve repair with the MitraClip system in the elderly: One
      year outcomes from the GRASP registry.
AB  - BACKGROUND: Although mitral regurgitation (MR) affects a relevant and increasing
      number of elderly, an optimal management of this high-risk population is
      challenging. METHODS AND RESULTS: The aim of this prospective, observational
      study was to compare one-year outcomes of MitraClip therapy in high surgical risk
      patients with moderate-to-severe or severe MR between patients aged <75 versus
      >=75years. A total of 180 patients were included: 92 were <75years and 88 were
      >=75years old. At one-year follow-up the primary efficacy endpoint (composite of
      death, surgery for mitral valve dysfunction and grade 3+ or 4+ MR) occurred in 41
      patients (24.5%), with similar rates between those aged <75years (23.9%) and
      those >=75years (25.2%), p=0.912. A total of 21 (12.2%) deaths were observed
      within 1year after the MitraClip procedure, without significant differences in
      cumulative mortality rates between elderly and younger patients (10.8% vs. 13.3%,
      respectively, p=0.574). Compared with baseline, the significant reduction in MR
      severity achieved after the procedure was sustained at one-year follow-up, in
      both elderly and younger patients and a significant improvement in NYHA
      functional class was observed in both groups. A total of 18 (10.0%) patients
      experienced a re-hospitalization for acute heart failure within one-year after
      the MitraClip procedure, with no significant differences between elderly and
      younger. At one-year follow-up both elderly and younger patients showed
      significant reductions in left ventricular volumes, with changes of similar
      extent between the two subgroups. CONCLUSIONS: MitraClip therapy can be
      considered a viable option also among subsets with more advanced age.

PMID- 27710785
TI  - TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function
      Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy.

PMID- 27710786
TI  - Vision Restoration Becomes Druggable.
AB  - In this issue of Neuron, Tochitsky et al. (2016) have identified the mechanism by
      which small-molecule photoswitches enter and specifically activate retinal OFF
      ganglion cells in degenerated retinas. This drug development is a tremendous step
      toward the treatment of blindness, regardless of the underlying mutation.

PMID- 27710783
TI  - Context Processing and the Neurobiology of Post-Traumatic Stress Disorder.
AB  - Progress in clinical and affective neuroscience is redefining psychiatric illness
      as symptomatic expression of cellular/molecular dysfunctions in specific brain
      circuits. Post-traumatic stress disorder (PTSD) has been an exemplar of this
      progress, with improved understanding of neurobiological systems subserving fear
      learning, salience detection, and emotion regulation explaining much of its
      phenomenology and neurobiology. However, many features remain unexplained and a
      parsimonious model that more fully accounts for symptoms and the core
      neurobiology remains elusive. Contextual processing is a key modulatory function
      of hippocampal-prefrontal-thalamic circuitry, allowing organisms to disambiguate
      cues and derive situation-specific meaning from the world. We propose that
      dysregulation within this context-processing circuit is at the core of PTSD
      pathophysiology, accounting for much of its phenomenology and most of its
      biological findings. Understanding core mechanisms like this, and their
      underlying neural circuits, will sharpen diagnostic precision and understanding
      of risk factors, enhancing our ability to develop preventive and "personalized"
      interventions.

PMID- 27710784
TI  - Direct Measurement of Correlation Responses in Drosophila Elementary Motion
      Detectors Reveals Fast Timescale Tuning.
AB  - Animals estimate visual motion by integrating light intensity information over
      time and space. The integration requires nonlinear processing, which makes motion
      estimation circuitry sensitive to specific spatiotemporal correlations that
      signify visual motion. Classical models of motion estimation weight these
      correlations to produce direction-selective signals. However, the correlational
      algorithms they describe have not been directly measured in elementary motion
      detecting neurons (EMDs). Here, we employed stimuli to directly measure responses
      to pairwise correlations in Drosophila's EMD neurons, T4 and T5. Activity in
      these neurons was required for behavioral responses to pairwise correlations and
      was predictive of those responses. The pattern of neural responses in the EMDs
      was inconsistent with one classical model of motion detection, and the timescale
      and selectivity of correlation responses constrained the temporal filtering
      properties in potential models. These results reveal how neural responses to
      pairwise correlations drive visual behavior in this canonical motion-detecting
      circuit.

PMID- 27710789
TI  - The Ventral Pallidum: Proposed Integrator of Positive and Negative Factors in
      Cocaine Abuse.
AB  - In this issue of Neuron, Creed et al. (2016) describe how cocaine produces
      divergent forms of plasticity at synapses between specific neurons in nucleus
      accumbens and ventral pallidum, and how these changes are associated with
      positive and negative reward behaviors.

PMID- 27710787
TI  - Clonally Related GABAergic Interneurons Do Not Randomly Disperse but Frequently
      Form Local Clusters in the Forebrain.
AB  - Progenitor cells in the medial ganglionic eminence (MGE) and preoptic area (PoA)
      give rise to GABAergic inhibitory interneurons that are distributed in the
      forebrain, largely in the cortex, hippocampus, and striatum. Two previous studies
      suggest that clonally related interneurons originating from individual MGE/PoA
      progenitors frequently form local clusters in the cortex. However, Mayer et al.
      and Harwell et al. recently argued that MGE/PoA-derived interneuron clones
      disperse widely and populate different forebrain structures. Here, we report
      further analysis of the spatial distribution of clonally related interneurons and
      demonstrate that interneuron clones do not non-specifically disperse in the
      forebrain. Around 70% of clones are restricted to one brain structure,
      predominantly the cortex. Moreover, the regional distribution of clonally related
      interneurons exhibits a clear clustering feature, which cannot occur by chance
      from a random diffusion. These results confirm that lineage relationship
      influences the spatial distribution of inhibitory interneurons in the forebrain.
      This Matters Arising paper is in response to Harwell et al. (2015) and Mayer et
      al. (2015), published in Neuron. See also the response by Turrero Garcia et al.
      (2016) and Mayer et al. (2016), published in this issue.

PMID- 27710788
TI  - Lineage Is a Poor Predictor of Interneuron Positioning within the Forebrain.
AB  - This Matters Arising Response paper addresses the Sultan et al. (2016) Matters
      Arising paper, published concurrently in Neuron. Clonally related excitatory
      neurons maintain a coherent relationship following their specification and
      migration. Whether cortical interneurons behave similarly is a fundamental
      question in developmental neuroscience. In Mayer et al. (2015), we reported that
      sibling interneurons disperse over several millimeters, across functional and
      anatomical boundaries. This finding demonstrated that clonality is not predictive
      of an interneuron's ultimate circuit specificity. Comparing the distribution of
      interneurons published in Mayer et al. to a random computer simulation, Sultan et
      al. suggest that clonally related interneurons are "not randomly dispersed." We
      argue that this comparison provides no insight into the influence of clonality on
      interneuron development because the entire population of cortical interneurons is
      "not randomly dispersed" in vivo. We find that the majority of cortical
      interneurons are similarly distributed whether or not they share a lineal
      relationship. Thus, at present there is no compelling evidence that clonality
      influences the position or function of interneurons.

PMID- 27710790
TI  - Lineage Relationships Do Not Drive MGE/PoA-Derived Interneuron Clustering in the
      Brain.
AB  - Neocortical excitatory and inhibitory neurons derive from distinct progenitor
      domains during embryonic development and migrate to their final positions, where
      they assemble into functional circuits. This process appears to be influenced by
      lineage relationships among locally born excitatory neurons, raising the
      intriguing possibility that this might be true for cortical interneurons. Two
      recent articles by the Fishell laboratory and our own used retrovirus-encoded DNA
      barcodes as unambiguous lineage-tracing tools to address this question, finding
      that clonally related inhibitory interneurons dispersed widely across the
      forebrain (Harwell et al., 2015; Mayer et al., 2015). This Matters Arising
      Response addresses the Sultan et al. (2016) Matters Arising paper, published
      concurrently in Neuron, where the authors reanalyze the datasets from both
      studies and propose a new interpretation, whereby clonally related interneurons
      would be considered clustered according to specific spatial constraints. After
      studying the report from Sultan et al. (2016) and carefully revisiting previously
      published studies, we find no evidence of lineage-dependent MGE/PoA-derived
      interneuron clustering in the forebrain.

PMID- 27710793
TI  - An Upside to Reward Sensitivity: The Hippocampus Supports Enhanced Reinforcement
      Learning in Adolescence.
AB  - Adolescents are notorious for engaging in reward-seeking behaviors, a tendency
      attributed to heightened activity in the brain's reward systems during
      adolescence. It has been suggested that reward sensitivity in adolescence might
      be adaptive, but evidence of an adaptive role has been scarce. Using a
      probabilistic reinforcement learning task combined with reinforcement learning
      models and fMRI, we found that adolescents showed better reinforcement learning
      and a stronger link between reinforcement learning and episodic memory for
      rewarding outcomes. This behavioral benefit was related to heightened prediction
      error-related BOLD activity in the hippocampus and to stronger functional
      connectivity between the hippocampus and the striatum at the time of
      reinforcement. These findings reveal an important role for the hippocampus in
      reinforcement learning in adolescence and suggest that reward sensitivity in
      adolescence is related to adaptive differences in how adolescents learn from
      experience.

PMID- 27710792
TI  - Principles of Synaptic Organization of GABAergic Interneurons in the Striatum.
AB  - The striatum, the entry nucleus of the basal ganglia, lacks laminar or columnar
      organization of its principal cells; nevertheless, functional data suggest that
      it is spatially organized. Here we examine whether the connectivity and synaptic
      organization of striatal GABAergic interneurons contributes to such spatial
      organization. Focusing on the two main classes of striatal GABAergic interneurons
      (fast-spiking interneurons [FSIs] and low-threshold-spiking interneurons
      [LTSIs]), we apply a combination of optogenetics and viral tracing approaches to
      dissect striatal microcircuits in mice. Our results reveal fundamental
      differences between the synaptic organizations of both interneuron types. FSIs
      target exclusively striatal projection neurons (SPNs) within close proximity and
      form strong synapses on the proximal somatodendritic region. In contrast, LTSIs
      target both SPNs and cholinergic interneurons, and synaptic connections onto SPNs
      are made exclusively over long distances and onto distal dendrites. These results
      suggest fundamentally different functions of FSIs and LTSIs in shaping striatal
      output.

PMID- 27710791
TI  - Subpallial Enhancer Transgenic Lines: a Data and Tool Resource to Study
      Transcriptional Regulation of GABAergic Cell Fate.
AB  - Elucidating the transcriptional circuitry controlling forebrain development
      requires an understanding of enhancer activity and regulation. We generated
      stable transgenic mouse lines that express CreERT2 and GFP from ten different
      enhancer elements with activity in distinct domains within the embryonic basal
      ganglia. We used these unique tools to generate a comprehensive regional fate map
      of the mouse subpallium, including sources for specific subtypes of amygdala
      neurons. We then focused on deciphering transcriptional mechanisms that control
      enhancer activity. Using machine-learning computations, in vivo chromosomal
      occupancy of 13 transcription factors that regulate subpallial patterning and
      differentiation and analysis of enhancer activity in Dlx1/2 and Lhx6 mutants, we
      elucidated novel molecular mechanisms that regulate region-specific enhancer
      activity in the developing brain. Thus, these subpallial enhancer transgenic
      lines are data and tool resources to study transcriptional regulation of
      GABAergic cell fate.

PMID- 27710794
TI  - Comparative approaches to escape.
AB  - Neural circuits mediating visually evoked escape behaviors are promising systems
      in which to dissect the neural basis of behavior. Behavioral responses to
      predator-like looming stimuli, and their underlying neural computations, are
      remarkably similar across species. Recently, genetic tools have been applied in
      this classical paradigm, revealing novel non-cortical pathways that connect loom
      processing to defensive behaviors in mammals and demonstrating that loom encoding
      models from locusts also fit vertebrate neural responses. In both invertebrates
      and vertebrates, relative spike-timing in descending pathways is a mechanism for
      escape behavior choice. Current findings suggest that experimentally tractable
      systems, such as Drosophila, may be applicable models for sensorimotor processing
      and persistent states in higher organisms.

PMID- 27710795
TI  - Common epigenetic variation in a European population of mentally healthy young
      adults.
AB  - DNA methylation represents an important link between structural genetic variation
      and complex phenotypes. The study of genome-wide CpG methylation and its relation
      to traits relevant to psychiatry has become increasingly important. Here, we
      analyzed quality metrics of 394,043 CpG sites in two samples of 568 and 319
      mentally healthy young adults. For 25% of all CpGs we observed medium to large
      common epigenetic variation. These CpGs were overrepresented in open sea and
      shore regions, as well as in intergenic regions. They also showed a strong
      enrichment of significant hits in association analyses. Furthermore, a
      significant proportion of common DNA methylation is at least partially
      genetically driven and thus may be observed similarly across tissues. These
      findings could be of particular relevance for studies of complex neuropsychiatric
      traits, which often rely on proxy tissues.

PMID- 27710797
TI  - Arsenic removal by discontinuous ZVI two steps system for drinking water
      production at household scale.
AB  - Different countries in Europe still suffer of elevated arsenic (As) concentration
      in groundwaters used for human consumption. In the case of households not
      connected to the distribution system, decentralized water supply systems, such as
      Point of Use (POU) and Point of Entry (POE), offer a direct benefit for the
      consumers. Field scale ex-situ treatment systems based on metallic iron (ZVI) are
      already available for the production of reduced volumes of drinking water in
      remote areas (village scale). To address drinking water needs at larger scale, we
      designed a pilot unit able to produce an elevated daily volume of water for human
      consumption. We tested the long-term As removal efficiency of a two steps ZVI
      treatment unit for the production of 400 L/day clean water based on the
      combination of ZVI corrosion process with sedimentation and retention of freshly
      formed Fe precipitates. The system treated 100 MUg/L As(V)-contaminated oxic
      groundwater in a discontinuous operation mode at a flow rate of 1 L/min for 31
      days. Final removal was 77-96% and the most performing step was
      aeration/sedimentation (A/S) tank with a 60-94% efficiency. Arsenic in the
      outflow slightly exceeded the drinking water limit of 10 MUg/L only after 6000 L
      treated and Fe concentration was always below 0.2 mg/L. Under proposed operating
      conditions ZVI passivation readily occurred and, as a consequence, Fe production
      sharply decreased. Arsenic mobility attached to particulate was 13-60% after ZVI
      column and 37-100% after A/S tank. Uniform amorphous cluster of Fe nanoparticles
      (100 nm) formed during aeration drove As removal process with an adsorption
      capacity corresponding to 20.5 mgAs/gFe. Research studies often focus only on
      chemico-physical aspects disregarding the importance of biological processes that
      may co-occur and interfere with ZVI corrosion, As removal and safe water
      production. We explored the microbial transport dynamics by flow cytometry,
      proved as a suitable tool to monitor the fate of both single cells and bioactive
      particles along the treatment train of the pilot unit. A net release of bioactive
      particles, representing on average 26.5% of flow cytometric events, was promoted
      by the ZVI filter, with densities 10 times higher than those found in the inflow.
      In conclusion, the proposed system was efficient to treat large daily volumes of
      As contaminated groundwater. However, filter design and operating conditions
      should be carefully adapted to specific situation, since several key factors
      affect As removal efficiency. An effort in the optimization of ZVI filter design
      should be made to reduce fast observed ZVI passivation and low As adsorption
      capacity of the whole filter. More attention to biomass retention and bioactive
      particles travelling within the unit should be given in order to elucidate
      bacteria influences on As removal efficiency and related sanitary risks on long
      term basis.

PMID- 27710796
TI  - Combined effect of TNF-alpha and cyclic stretching on gene and protein expression
      associated with mineral metabolism in cementoblasts.
AB  - OBJECTIVE: This work aims to investigate how the combination of TNF-alpha and
      cyclic stretching affects the expression of gene and protein associated with
      mineral metabolism in cementoblasts in vitro. DESIGN: Cementoblasts were
      cyclically stretched using the Flexcell tension system 4000 in the presence of 10
      ng/ml TNF-alpha. Subsequently, the gene and protein expression CAP, Col I, BSP,
      OPG, RANKL and RUNX2 were detected using RT- PCR and ELISA/Western immunoblotting
      methods, respectively. RESULTS: Cyclic stretching alone enhanced CAP, Col I, OPG,
      RANKL and RUNX2 expression in an amplitude manner, while decreased BSP
      expression. Expression of all these proteins was attenuated in the presence of
      TNF-alpha whether the cells were exposed to cyclic stretching or not. The ratio
      of RANKL/OPG was increased at any stimulation. CONCLUSION: This results suggest
      that TNF-alpha affected the regulation of gene and protein expression induced by
      mechanical stimulation in cementoblasts. This may suppress anabolism and promote
      catabolism of cementum. It suggests that inflammatory cytokine may impair the
      cementum remodeling under mechanical stimulation.

PMID- 27710798
TI  - Removal of triazine-based pollutants from water by carbon nanotubes: Impact of
      dissolved organic matter (DOM) and solution chemistry.
AB  - Adsorption of organic pollutants by carbon nanotubes (CNTs) in the environment or
      removal of pollutants during water purification require deep understanding of the
      impacts of the presence of dissolved organic matter (DOM). DOM is an integral
      part of environmental systems and plays a key role affecting the behavior of
      organic pollutants. In this study, the effects of solution chemistry (pH and
      ionic strength) and the presence of DOM on the removal of atrazine and
      lamotrigine by single-walled CNTs (SWCNTs) was investigated. The solubility of
      atrazine slightly decreased (~5%) in the presence of DOM, whereas that of
      lamotrigine was significantly enhanced (by up to ~70%). Simultaneous introduction
      of DOM and pollutant resulted in suppression of removal of both atrazine and
      lamotrigine, which was attributed to DOM-pollutant competition or blockage of
      adsorption sites by DOM. However the decrease in removal of lamotrigine was also
      a result of its complexation with DOM. Pre-introduction of DOM significantly
      reduced pollutant adsorption by the SWCNTs, whereas introduction of DOM after the
      pollutant resulted in the release of adsorbed atrazine and lamotrigine from the
      SWCNTs. These data imply that DOM exhibits higher affinity for the adsorption
      sites than the triazine-based pollutants. In the absence of DOM atrazine was a
      more effective competitor than lamotrigine for adsorption sites in SWCNTs.
      However, competition between pollutants in the presence of DOM revealed
      lamotrigine as the better competitor. Our findings help unravel the complex DOM
      organic pollutant-CNT system and will aid in CNT-implementation in water
      purification technologies.

PMID- 27710799
TI  - Trace levels of sewage effluent are sufficient to increase class 1 integron
      prevalence in freshwater biofilms without changing the core community.
AB  - Most river systems are impacted by sewage effluent. It remains unclear if there
      is a lower threshold to the concentration of sewage effluent that can
      significantly change the structure of the microbial community and its mobile
      genetic elements in a natural river biofilm. We used novel in situ mesocosms to
      conduct replicated experiments to study how the addition of low-level
      concentrations of sewage effluent (nominally 2.5 ppm) affects river biofilms in
      two contrasting Chalk river systems, the Rivers Kennet and Lambourn (high/low
      sewage impact, respectively). 16S sequencing and qPCR showed that community
      composition was not significantly changed by the sewage effluent addition, but
      class 1 integron prevalence (Lambourn control 0.07% (SE +/- 0.01), Lambourn
      sewage effluent 0.11% (SE +/- 0.006), Kennet control 0.56% (SE +/- 0.01), Kennet
      sewage effluent 1.28% (SE +/- 0.16)) was significantly greater in the communities
      exposed to sewage effluent than in the control flumes (ANOVA, F = 5.11, p =
      0.045) in both rivers. Furthermore, the difference in integron prevalence between
      the Kennet control (no sewage effluent addition) and Kennet sewage-treated
      samples was proportionally greater than the difference in prevalence between the
      Lambourn control and sewage-treated samples (ANOVA (interaction between treatment
      and river), F = 6.42, p = 0.028). Mechanisms that lead to such differences could
      include macronutrient/biofilm or phage/bacteria interactions. Our findings
      highlight the role that low-level exposure to complex polluting mixtures such as
      sewage effluent can play in the spread of antibiotic resistance genes. The
      results also highlight that certain conditions, such as macronutrient load, might
      accelerate spread of antibiotic resistance genes.

PMID- 27710800
TI  - Noninvasive assessment of myocardial bridging by coronary flow velocity reserve
      with transthoracic Doppler echocardiography: vasodilator vs. inotropic
      stimulation.
AB  - BACKGROUND: To consider hemodynamic assessment of myocardial bridging (MB)
      adequate, it is believed that inotropic stimulation with dobutamine should be
      estimated because its dynamic nature depends on the degree of extravascular
      coronary compression. This study evaluated comparative assessment of hemodynamic
      relevance of MB using coronary flow velocity reserve (CFVR) measurements by
      transthoracic Doppler echocardiography (TTDE) with vasodilatative and inotropic
      challenges. METHODS: This prospective study included forty-four patients with
      angiographic evidence of isolated MB of the left anterior descending coronary
      artery (LAD) and systolic compression of >=50% diameter stenosis. All patients
      were evaluated by exercise stress-echocardiography (ExSE) test for signs of
      myocardial ischemia, and CFVR of the distal segment of LAD during iv.infusion of
      adenosine (ADO:140MUg/kg/min) and iv.infusion of dobutamine (DOB:10
      40MUg/kg/min), separately. RESULTS: Exercise-SE was positive for myocardial
      ischemia in 8/44 (18%) of patients. CFVR during ADO was significantly higher than
      CFVR during peak DOB (2.85+/-0.68 vs. 2.44+/-0.48, p=0.002). CFVR during peak DOB
      was significantly lower in SE-positive group in comparison to SE-negative group
      (2.01+/-0.16 vs. 2.54+/-0.47, p<0.001), but not for ADO (2.47+/-0.51 vs. 2.89+/
      0.70, p=0.168), respectively. Multivariable logistic analysis showed that CFVR
      peak DOB was the most significant predictor of functional significant MB (OR
      0.011, 95%CI: 0.001-0.507, p=0.021). Receiver-operating characteristic curves
      have shown that TTDE-CFVR obtained by high-dose of dobutamine infusion is better
      than those by adenosine regarding to functional status of MB (AUC 0.861, p=0.004;
      AUC 0.674, p=0.179, respectively). CONCLUSIONS: Non-invasive CFVR measurement by
      TTDE during inotropic stimulation, in comparison to vasodilation, provides more
      reliable functional evaluation of MB.

PMID- 27710801
TI  - Risk scores for contrast-induced nephropathy after percutaneous coronary
      intervention.

PMID- 27710802
TI  - Long-term survival among patients with coronary angioplasty with drug eluting
      stent for the treatment of unprotected left main stenosis compared to coronary
      artery bypass grafting.

PMID- 27710804
TI  - Acute inferolateral myocardial infarction: The cause or the effect of takotsubo
      syndrome?

PMID- 27710803
TI  - Clinical outcome of statin plus ezetimibe versus high-intensity statin therapy in
      patients with acute myocardial infarction propensity-score matching analysis.
AB  - BACKGROUND: It is unclear whether simvastatin-ezetimibe could be an alternative
      therapy to high-intensity statin therapy in high-risk patients. The aim of this
      study was to compare the clinical outcomes of simvastatin-ezetimibe and high
      intensity statin therapy in patients with acute myocardial infarction (AMI), and
      especially in those with high-risk factor. METHODS: A total of 3520 AMI patients
      in the KAMIR (Korea Acute Myocardial Infarction Registry) were classified into
      simvastatin-ezetimibe group (n=1249) and high-intensity statin group (n=2271).
      Multivariate analysis and propensity-score matching analysis were performed. The
      primary endpoint was major adverse cardiac events (MACE) at 12-months follow-up.
      RESULTS: In overall AMI patients, MACE occurred in 116 patients (9.3%) in
      simvastatin-ezetimibe group and 116 patients (5.1%) in high-intensity statin
      group. The difference in MACE between groups was driven by repeat
      revascularization (5.9% vs. 2.2%). After propensity matching analysis,
      simvastatin-ezetimibe was associated with a higher incidence of MACE than high
      intensity statin therapy (adjusted hazard ratio: 3.090, 95% confidence interval:
      1.715 to 5.566, p<0.001). However, in patients with high-risk factors, such as
      diabetes, old age, or heart failure, simvastatin-ezetimibe had similar incidence
      of MACE compared with high-intensity statin therapy in further adjusted analysis.
      CONCLUSIONS: In overall AMI patients, high-intensity statin therapy had better
      clinical outcomes than simvastatin-ezetimibe. However, in patients with high-risk
      factor, simvastatin-ezetimibe had comparable clinical outcomes to high-intensity
      statin therapy. Therefore, simvastatin-ezetimibe could be used as an alternative
      to high-intensity statin therapy in such patients.

PMID- 27710805
TI  - Protein levels in Keap1-Nrf2 system in human failing heart.

PMID- 27710806
TI  - Sleep-related changes in cardiovascular autonomic regulation in left coronary
      artery ligation rats: Neural mechanism facilitating arrhythmia after myocardial
      infarction.
AB  - BACKGROUND: Autonomic imbalance with increased sympathetic and decreased
      parasympathetic activities is observed in patients after myocardial infarction
      (MI). We aimed to investigate sleep-related changed in autonomic regulation in
      left coronary artery (LCA) ligation rats. METHODS: Wireless transmission of
      polysomnographic recording was performed in sham and LCA ligation male rats
      during normal daytime sleep with and without atenolol treatment. Spectral
      analyses of the electroencephalogram (EEG) and electromyogram (EMG) were
      evaluated to define active waking (AW), quiet and paradoxical sleeps (QS, PS).
      Cardiac autonomic activities were measured by analyzing the power spectrum of
      heart rate variability (HRV). EEG, EMG and HRV were recorded over 6h for
      consecutive 3days in all groups. RESULTS: In LCA ligation group, there were
      higher LF and LF/HF ratio on QS phase, but not AW and PS phases, compared to
      atenolol treated sham and LCA ligation groups, respectively. The HF component was
      not significantly changed on all groups in both sleep and awake phases. Sleep
      interruption was more frequent in LCA ligation rats compared to sham, and it was
      not found in LCA ligation with atenolol treatment group. Increased AW, PS and
      decreased QS time were noted in LCA ligation group, compared to sham and it was
      restored to baseline in LCA ligation with atenolol treatment group. CONCLUSIONS:
      Our results demonstrate significant sleep fragmentations with sympathetic
      hyperactivity during QS stages after MI, and atenolol could restore the autonomic
      dysfunction and sleep disturbance. The finding explains the cause of sleep
      related fetal arrhythmia and sudden cardiac death after MI.

PMID- 27710807
TI  - Cognitive and functional changes associated with Abeta pathology and the
      progression to mild cognitive impairment.
AB  - Cognitively-normal people with evidence of beta-amyloid (Abeta) pathology and
      subtle cognitive dysfunction are believed to be at high risk for progression to
      mild cognitive impairment due to Alzheimer's disease (AD). Clinical trials in
      later stages of AD typically include a coprimary endpoint to demonstrate efficacy
      on both cognitive and functional assessments. Recent trials focus on cognitively
      normal people, but functional decline has not been explored for trial designs in
      this group. The goal of this study was therefore to characterize cognitive and
      functional decline in (1) cognitively-normal people converting to mild cognitive
      impairment (MCI) and (2) cognitively-normal beta-amyloid-positive (Abeta+)
      people. Specifically, we sought to identify and compare the cognitive and
      functional assessments and their weighted combinations that maximize the
      longitudinal decline specific to these 2 groups. We studied 68 people who
      converted from normal cognition to MCI and 70 nonconverters, as well as 137
      Abeta+ and 210 beta-amyloid-negative cognitively-normal people. We used bootstrap
      aggregation and cross-validated mixed-models to estimate the distribution of
      weights applied to cognitive and functional outcomes to form composites. We also
      evaluated best subset optimization. Using optimized composites, we estimated
      statistical power for a variety of clinical trial scenarios. Overall, 55.4% of
      cognitively-normal to MCI converters were Abeta+. Large gains in power estimates
      were obtained when requiring participants to have both subtle cognitive
      dysfunction and Abeta pathology compared with requiring Abeta pathology alone.
      Additional power resulted when including functional as well as cognitive outcomes
      as part of the composite. Composites formed by applying equal weights to all
      measures provided the highest estimates of cross-validated power, although
      similar to both continuous weight optimization and best subset optimization.
      Using a composite to detect a 30% slowing of decline, 80% power was obtained for
      predicted Abeta+ converters with 375 completers/arm for a 30-month trial using a
      combination of cognitive/ functional measures. In the Abeta+ group, power to
      approach levels suitable for a phase III clinical trial would require
      considerably larger sample sizes. Composites incorporating both cognitive and
      functional measures may substantially increase the power of a trial in a
      preclinical (Abeta+) AD population with subtle evidence of cognitive dysfunction.

PMID- 27710808
TI  - Coronary atheroma progression rates in men and women following high-intensity
      statin therapy: A pooled analysis of REVERSAL, ASTEROID and SATURN.
AB  - BACKGROUND AND AIMS: High-intensity statin therapy (HIST) reduces cardiovascular
      events, however, sex-related differences in treatment effects are not well
      characterized. METHODS: A patient-level post hoc pooled analysis of 3 randomized
      trials utilizing serial coronary intravascular ultrasound was undertaken, testing
      the anti-atherosclerotic effects of HIST in coronary disease patients. Sex
      related differences in changes (Delta) in coronary percent atheroma volume (PAV)
      were ascertained following 18-24 months of HIST (atorvastatin 80 mg or
      rosuvastatin 40 mg daily), and further characterized according to on-treatment
      lipid and lipoprotein levels. RESULTS: In women (n = 451) compared with men (n =
      1190), on-treatment levels of LDL-C (68 +/- 24 vs. 67 +/- 22 mg/dl, p=0.62) and
      apoB (77 +/- 23 vs. 76 +/- 20 mg/dL, p=0.51) were similar; levels of HDL-C (53 +/
      12 vs. 47 +/- 11 mg/dl, p < 0.001), apoA1 (154 +/- 26 vs. 140 +/- 24 mg/dl, p <
      0.001), triglycerides [122 (95, 158) vs. 114 (89, 154) mg/dl, p=0.012] and CRP
      [1.7 (0.9, 3.8) vs. 1.1 (0.6, 2.7) mg/l, p < 0.001] were higher; while the total
      cholesterol/HDL-C (TC/HDL-C) ratio was lower (2.9 +/- 0.8 vs. 3.1 +/- 0.8, p <
      0.001). Compared with men, women harbored significantly lower baseline PAV (34.8
      +/- 8.7 vs. 38.3 +/- 8.8%, p < 0.001), yet demonstrated significantly greater PAV
      regression (DeltaPAV -1.07 +/- 0.26 vs. -0.66 +/- 0.23%, p=0.02). When achieved
      on-treatment levels of LDL-C were <64 mg/dl, apoB <73 mg/dl, non-HDL-C <88.8
      mg/dl, and TC/HDL-C <2.99, women demonstrated significantly greater PAV
      regression than men. Multivariable analysis revealed female sex to independently
      associate with PAV regression (coefficient -0.66, p=0.02). CONCLUSIONS: Women
      demonstrate greater degrees of coronary plaque regression compared with men
      following long-term HIST, especially in the setting of lower achieved atherogenic
      lipoprotein levels.

PMID- 27710809
TI  - An experimental and theoretical study on a novel donor-pi-acceptor bridge type 2,
      4, 5-trimethoxy-4'-chlorochalcone for optoelectronic applications: A dual
      approach.
AB  - In this article the authors aim is to investigate and analyze the various key
      parameters of an organic D-pi-A type novel nonlinear optical material 2, 4, 5
      trimethoxy-4'-chlorochalcone (2,4,5TMCC) through experimental and quantum
      chemical studies. The Claisen-Schmidt condensation reaction mechanism was applied
      to synthesize the 2,4,5TMCC compound and its single crystal was grown by a slow
      evaporation solution growth (low cost) technique. The crystal structure was
      confirmed by powder X-ray diffraction analysis. The robust vibrational study has
      been done using FT-IR and FT-Raman spectra and its NLO activity was discussed.
      The factor group analysis was also performed. The optical absorption spectrum was
      recorded and the band gap was calculated to be 2.8eV. In photoluminescence
      spectrum, an intense emission band at ~540nm has been observed which shows that
      the grown crystals can be used in green organic light emitting diodes and laser
      applications. To achieve the stable ground state molecular geometry of 2,4,5TMCC,
      the computational techniques were applied at different levels of theory using 6
      31G* basis set. The calculated geometrical parameters and vibrational spectra are
      found to be in good agreement with the experimental results. To probe the optical
      properties of the title compound the time dependent density functional theory was
      applied. The excitation wavelength was observed at ~398.63nm calculated at
      B3LYP/6-31G* level of theory and found close to experimental value (i.e. 396nm).
      The static first hyperpolarizability value is found to be 136 times higher than
      prototype urea molecule. Additionally, the molecular level approach was attained
      as HOMO-LUMO gap and electrostatic potential maps. The DSC study reveals that the
      titled material is stable up to 149 degrees C. The photophysical and nonlinear
      optical properties suggest that the titled material could be a better choice for
      the fabrication of optoelectronic devices.

PMID- 27710810
TI  - A highly selective fluorescent probe based on Michael addition for fast detection
      of hydrogen sulfide.
AB  - A new 4-hydroxy-1,8-naphthalimide-based compound (probe 1) has been designed and
      synthesized. The colorimetric and fluorescent properties of probe 1 towards
      hydrogen sulfide (H2S) were investigated in detail. The results show that the
      probe 1 could selectively and sensitively recognize H2S rather than other
      reactive sulfur species. The reaction mechanism of this probe is an
      intramolecular cyclization caused by the Michael addition of H2S to give 4
      hydroxy-1,8-naphthalimide. The intramolecular charge transfer of 4-hydroxy-1,8
      naphthalimide is significant. Probe 1 quickly responded to H2S and showed a 75
      fold fluorescence enhancement in 5min. Moreover, probe 1 could detect H2S
      quantitatively with a detection limit as low as 0.23MUM.

PMID- 27710811
TI  - Interprofessional education in the clinical setting: A qualitative look at the
      preceptor's perspective in training advanced practice nursing students.
AB  - With the shift towards interprofessional education to promote collaborative
      practice, clinical preceptors are increasingly working with trainees from various
      professions to provide patient care. It is unclear whether and how preceptors
      modify their existing precepting approach when working with trainees from other
      professions. There is little information on strategies for this type of
      precepting, and how preceptors may foster or impede interprofessional
      collaboration. The purpose of this qualitative description pilot study was to
      identify current methods preceptors use to teach trainees from other professions
      in the clinical setting, particularly advanced practice nursing and medical
      trainees, and to identify factors that support or impede this type of precepting.
      Data collected through observations and interviews were analyzed by the research
      team using thematic analysis procedures. Three major themes were identified: 1) a
      variety of teaching approaches and levels of engagement with trainees of
      different professions, 2) preceptor knowledge gaps related to curricula, goals,
      and scope of practice of trainees from other professions, and 3) administrative,
      structural and logistical elements that impact the success of precepting trainees
      from different professions in the clinical setting. This study has implications
      for faculty development and evaluation of current precepting practices in
      clinical settings.

PMID- 27710812
TI  - Neck range of motion following cervical spinal fusion: A comparison of patient
      centered and objective assessments.
AB  - OBJECTIVES: A common question posed by patients undergoing cervical fusion
      pertains to the likelihood of perceiving a postoperative limitation in neck
      mobility. The aim of this study was to assess the change in neck mobility after
      subaxial cervical fusion using an objective range of motion (ROM) measure and
      patient reported assessment. PATIENTS AND METHODS: Patients older than 18 years
      of age, undergoing first-time anterior or posterior subaxial cervical arthrodesis
      for a symptomatic spondylotic process (radiculopathy, cervical spondylotic
      myelopathy or primary neck pain) at a single center were eligible. Assessment
      included: 1) neck pain on a numeric rating scale; 2) four-directional objective
      neck mobility using the validated cervical ROM goniometer; and 3) a novel
      Mobility Assessment Scale (MAS) for patient perceived neck mobility. Subjects
      were dichotomized by number of levels fused (1-2 levels and >=3 levels). RESULTS:
      There were 25 patients with a mean of 2.7+/-1.5 levels fused. Neck pain was
      improved in both groups with mean change of -3.4 [95% CI -4.7,-2.1], p=0.004 for
      1-2 levels and -3.5 [95% CI -5.4,-1.5], p=0.009 for >=3 levels. MAS score
      improved significantly in group undergoing 1-2 level fusion (-1.8 [95% CI: -3.1,
      0.4], p=0.016) but not in those with >=3 levels fused. There was a significant
      positive correlation between MAS and neck pain in the 1-2 level fusion group
      (rs=0.667, p=0.012) but not in the >=3 level group. Objective neck mobility did
      not changed significantly in either group. CONCLUSIONS: Patient reported neck
      mobility was significantly improved following 1-2 level cervical fusion. This
      change correlated significantly with patient reported improvement in neck pain.
      No significant difference in reported neck mobility was found in those undergoing
      fusion of >=3 levels.

PMID- 27710813
TI  - Potential clinical indications for a CCK2 receptor antagonist.
AB  - Gastrin controls gastric acid secretion and mucosal cell growth, especially of
      enterochromaffin-like cells, via gastrin/cholecystokinin-2 receptor (CCK2R)
      binding and downstream signalling. Studies in animal models, healthy subjects and
      patients with gastric neuroendocrine tumours provide compelling evidence to
      justify developing a CCK2R antagonist (CCK2RA) for preventing or treating the
      trophic effects of hypergastrinaemia or conditions expressing CCK2R, and with or
      without a proton pump inhibitor, for treating gastric acid-related conditions.
      Many compounds have been studied, but most have had problems with potency,
      selectivity for CCK2 versus CCK1 receptor, solubility or oral bioavailability.
      None has yet been marketed. Netazepide and Z-360 are currently undergoing
      clinical development, for treatment of gastric neuroendocrine tumours and
      pancreatic cancer, respectively. There are several other potential indications
      for a CCK2RA and an unmet need.

PMID- 27710814
TI  - Structure and genetics of the O-antigens of Escherichia coli O182-O187.
AB  - O-polysaccharides (OPSs) were obtained by mild acid degradation of the
      lipopolysaccharides of Escherichia coli O182-O187, and their structures were
      established by sugar analysis, Smith degradation, and 1H and 13C NMR
      spectroscopy. In addition to the monosaccharides that occur often in E. coli OPSs
      (d-Glc, d-Gal, d-Man, d-GlcNAc, d-GalNAc, d-GlcA, l-Fuc, d-Rib), a number of less
      common components were identified as the OPS constituents, including 2-acetamido
      2-deoxy-l-quinovose and 4-deoxy-4-[(S)-3-hydroxybutanoyl-l-alanyl]-d-quinovose
      (O186), 3-acetamido-3-deoxy-d-fucose (O187), 3-deoxy-3-[(R)-3-hydroxybutanoyl]-d
      fucose (O184), and 2,3-diacetamido-2,3-dideoxy-l-rhamnose (O182). The OPS
      structures of E. coli O183 and O182 are identical to those of the OPS of Shigella
      boydii type 10 and the capsular polysaccharide of E. coli K48, respectively. The
      OPSs of E. coli O186 and O123 are closely related differing in the presence of a
      Glc residue in the former in place of a GlcNAc residue in the latter. The O
      antigen gene clusters of the bacteria studied were analyzed and their contents
      were found to be consistent with the OPS structures. Predicted
      glycosyltransferases encoded in the gene clusters were tentatively assigned to
      glycosidic linkages based on similarities to sequences of other E. coli O
      serogroups available from GenBank and taking into account the OPS structures
      established.

PMID- 27710815
TI  - Multivalent S-sialoside protein conjugates block influenza hemagglutinin and
      neuraminidase.
AB  - A new class of S-sialoside Human Serum Albumin (HSA) and Bovine Serum Albumin
      (BSA) conjugates were prepared to enhance the binding affinity to hemagglutinin
      (HA) and neuraminidase (NA). The valency of glycoconjugates was controlled by the
      reaction ratio of the S-sialoside monomer and protein. Hemagglutination
      inhibition assay showed that these synthetic glycoproteins have higher affinity
      to HA than the small clusters of sialosides with lower valency, due to
      multivalent effect and optimized three dimensional presentation of sialosides on
      the protein platform. The results of fluorescent NA inhibition assay showed that
      some of the conjugates have moderate NA inhibitory activity, in comparison to the
      monomer and low valent conjugates with weak or none inhibitory activity. These
      synthetic sialylated proteins were not cytotoxic with concentrations up to 100
      MUM, since the sialylation did not change the secondary structure of protein.
      This new kind of conjugates can be used as lead compounds for antiviral drug
      design and the construction of pseudo sialoside-protein conjugates library to
      investigate the carbohydrate-HA/NA recognition process and a platform for the
      influenza virus capturing.

PMID- 27710816
TI  - Analysis of stochastic crystallization in micron-sized droplets of undercooled
      liquid l-arabitol.
AB  - Kinetics of isothermal crystallization of l-arabitol were analyzed from the
      undercooled liquid state within micron-sized droplets from micro-Raman
      spectroscopy. This study reveals that crystallization slightly above Tg is
      controlled by stochastic heterogeneous nucleation inherent to the droplet size.
      Microscopic Raman investigations performed in droplets give the unique
      opportunity to analyze the pure metastable Form II of l-arabitol. It was found
      that Form II is characterized by a molecular packing more compact than that of
      the stable Form I, inherent to strong intermolecular hydrogen bonding. Kinetics
      laws obtained by analyzing several droplets at different temperatures, reveal the
      transient character of Form II, quasi systematically detected during the
      crystallization process of form I. Form II appears as the first step of
      crystallization prior to successive short-living metastable states which is
      necessary to achieve a complete crystallization in Form I. It was found that the
      kinetics of conversion between the metastable states (Form II) into Form I is
      dependent on the amount of strong hydrogen bonding distinctive of Form II.

PMID- 27710817
TI  - Development and evaluation of a newborn care education programme in primiparous
      mothers in Nepal.
AB  - BACKGROUND: the health and survival of newborns depend on high levels of
      attention and care from caregivers. The growth and development of some infants
      are unhealthy because of their mother's or caregiver's lack of knowledge or the
      use of inappropriate or traditional child-rearing practices that may be harmful.
      OBJECTIVE: to develop a newborn care educational programme and evaluate its
      impact on infant and maternal health in Nepal. DESIGN: a randomised controlled
      trial. PARTICIPANTS: one hundred and forty-three mothers were randomly assigned
      to the intervention (n=69) and control (n=74) groups. Eligible participants were
      primiparous mothers who had given birth to a single, full-term, healthy infant,
      and were without a history of obstetric, medical, or psychological problems.
      METHODS: prior to being discharged from the postnatal unit, the intervention
      group received our structured newborn care education programme, which consisted
      of one-on-one educational sessions lasting 10-15minutes each and one postpartum
      follow-up telephone support within two weeks after discharge, in addition to the
      hospital's routine general newborn care education. The control group received
      only the regular general newborn care education. Outcomes were measured by using
      Newborn care Knowledge Questionnaires, Karitane Parenting Confidence Scale, State
      Trait Anxiety Inventory for Adults and infant health and care status. FINDINGS:
      the number of mothers attending the health centre due to the sickness of their
      babies was significantly decreased in the intervention group compared to the
      control group. Moreover, the intervention group had significant increases in
      newborn care knowledge and confidence, and decreases in anxiety, compared with
      the control group. CONCLUSIONS: the structured newborn care education programme
      enhanced the infant and mother health. Moreover, it increased maternal knowledge
      of newborn care and maternal confidence; and reduced anxiety in primiparous
      mothers. Thus, this educational programme could be integrated into routine
      educational programs to promote maternal and infant well-being in Nepalese
      society.

PMID- 27710818
TI  - Attentional orienting and executive control are affected by different types of
      meditation practice.
AB  - Several studies have demonstrated the beneficial effects of meditation on
      attention. The present study investigated the relationship between focused
      attention (FA) and open monitoring (OM) meditation skills and the various
      functions of attention. In Experiment 1, we executed the attention network test
      and compared the performance of experts on dandao meditation with that of
      ordinary people on this test. The results indicated that the experts specializing
      in OM meditation demonstrated greater attentional orienting ability compared with
      those specializing in FA meditation and the control group. In addition, both
      expert groups registered improvements in their executive control abilities
      compared with the control group. In Experiment 2, we trained beginners in FA
      meditation for 3months. The results showed that the experimental group exhibited
      significantly enhanced executive control ability. We infer that FA meditation
      skills promote executive control function and OM meditation skills promote both
      executive control and attentional orienting functions.

PMID- 27710819
TI  - Severe fatigue in type 1 diabetes: Exploring its course, predictors and
      relationship with HbA1c in a prospective study.
AB  - AIMS: To prospectively identify the course of severe fatigue, its predictors and
      the relationship with HbA1c in patients with type 1 diabetes. METHODS: 214 adult
      patients completed questionnaires on fatigue severity and fatigue-related factors
      at baseline. HbA1c was retrieved from medical records. After 43months, fatigue
      severity and HbA1c were reassessed in 194 patients. A logistic regression
      analysis was used to determine predictors of severe fatigue at follow-up with
      various cognitive-behavioral and clinical factors as potential predictors. The
      relationship between fatigue and HbA1c was investigated in a sub-analysis by
      differentiating between patients with suboptimal glucose control [HbA1c>7%
      (53mmol/mol)] and optimal glucose control [HbA1c?7% (53mmol/mol)]. RESULTS: The
      prevalence of severe fatigue was 40% at baseline and 42% at follow-up. In three
      out of four severely fatigued patients at baseline (76%), severe fatigue
      persisted over time. More depressive symptoms, more pain, sleep disturbances,
      lower self-efficacy concerning fatigue, less confidence in diabetes self-care,
      more fatigue severity at baseline and more diabetes complications predicted
      severe fatigue at follow-up. Over time, HbA1c at baseline was positively
      associated with fatigue severity at follow-up in both groups (suboptimal glucose
      control: r=.18, p<.05; optimal glucose control: r=.09, p<.05). CONCLUSIONS: About
      three quarters of fatigued[corrected] patients with type 1 diabetes suffer from
      persistent fatigue. Aside from the number of diabetes complications, no clinical
      factors explained the persistence of fatigue. HbA1c and fatigue were weakly
      associated in a sub-analysis. Since the strongest predictors of severe fatigue
      were cognitive-behavioral factors, behavioral interventions might be effective in
      decreasing fatigue.

PMID- 27710822
TI  - Effect of spacer length on the interfacial behavior of N,N'-bis(dimethylalkyl)
      alpha,omega-alkanediammonium dibromide gemini surfactants in the absence and
      presence of ZnO nanoparticles.
AB  - In this paper the interfacial behavior of aqueous solutions of cationic gemini
      surfactants of the, N,N'-bis(dimethylalkyl)-alpha,omega-alkanediammoniumdibromide
      type (known as the 12-s-12 series), in the absence and presence of ZnO
      nanoparticles was studied. Equilibrium and dynamic interfacial tension between n
      decane and aqueous surfactant solutions were investigated. It was concluded that
      the synergistic effect between surfactants and nanoparticles increases the
      surfactant efficiency with respect to reducing the interfacial tension. Moreover,
      the magnitude of the effect of ZnO nanoparticles on the interfacial tension
      decreases with increasing length of the spacer group in the gemini surfactant
      structure. Dynamic studies illustrate that the migration mechanism of gemini
      surfactants (regardless of the presence of ZnO) from the bulk to the interface
      was controlled by both diffusion and adsorption. The effect of spacer length on
      the contact angle and emulsion stability both with and without nanoparticles was
      also studied.

PMID- 27710820
TI  - Geographical variation in the progression of type 2 diabetes in Peru: The
      CRONICAS Cohort Study.
AB  - BACKGROUND: The study aims were to estimate the incidence and risk factors for
      T2D in four settings with different degree of urbanization and altitude in Peru.
      METHODS: Prospective cohort study conducted in urban, semi-urban, and rural areas
      in Peru. An age- and sex-stratified random sample of participants was taken from
      the most updated census. T2D was defined as fasting blood glucose ?7.0mmol/L or
      taking anti-diabetes medication. Exposures were divided into two groups:
      geographical variables (urbanization and altitude), and modifiable risk factors.
      Incidence, relative risks (RR), 95% confidence intervals (95%CI), and population
      attributable fractions (PAF) were estimated. RESULTS: Data from 3135
      participants, 48.8% males, mean age 55.6years, was analyzed. Overall baseline
      prevalence of T2D was 7.1% (95%CI 6.2-8.0%). At follow-up, including 6207 person
      years of follow-up, a total of 121 new T2D cases were accrued, equating to an
      incidence of 1.95 (95%CI 1.63-2.33) per 100 person-years. There was no urban to
      rural gradient in the T2D incidence; however, compared to sea level sites,
      participants living in high altitude had a higher incidence of diabetes (RR=1.58;
      95%CI 1.01-2.48). Obesity had the highest attributable risk for developing T2D,
      although results varied by setting, ranging from 14% to 80% depending on
      urbanization and altitude. CONCLUSIONS: Our results suggest that the incidence of
      T2D was greater in high altitude sites. New cases of diabetes were largely
      attributed to obesity, but with substantial variation in the contribution of
      obesity depending on the environment. These findings can inform appropriate
      context-specific strategies to reduce the incidence of diabetes.

PMID- 27710821
TI  - Effects of linagliptin monotherapy compared with voglibose on postprandial blood
      glucose responses in Japanese patients with type 2 diabetes: Linagliptin Study of
      Effects on Postprandial blood glucose (L-STEP).
AB  - AIMS: To compare the efficacy on glycemic parameters between a 12-week
      administration of once-daily linagliptin and thrice-daily voglibose in Japanese
      patients with type 2 diabetes. METHODS: In a multi-center, randomized, parallel
      group study, 382 patients with diabetes were randomized to the linagliptin group
      (n=192) or the voglibose group (n=190). A meal tolerance test was performed at
      weeks 0 and 12. Primary outcomes were the change from baseline to week 12 in
      serum glucose levels at 2h during the meal tolerance test, HbA1c levels, and
      serum fasting glucose levels, which were compared between the 2 groups. RESULTS:
      Whereas changes in serum glucose levels at 2h during the meal tolerance test did
      not differ between the groups, the mean change in HbA1c levels from baseline to
      week 12 in the linagliptin group (-0.5+/-0.5% [-5.1+/-5.4mmol/mol]) was
      significantly larger than in the voglibose group (-0.2+/-0.5% [-2.7+/
      5.4mmol/mol]). In addition, there was significant difference in changes in serum
      fasting glucose levels (-0.51+/-0.95mmol/L in the linagliptin group vs. -0.18+/
      0.92mmol/L in the voglibose group, P<0.001). The incidences of hypoglycemia,
      serious adverse events (AEs), and discontinuations due to AEs were low and
      similar in both groups. However, gastrointestinal AEs were significantly lower in
      the linagliptin group (1.05% vs. 5.85%; P=0.01). CONCLUSIONS: These data
      suggested that linagliptin monotherapy had a stronger glucose-lowering effect
      than voglibose monotherapy with respect to HbA1c and serum fasting glucose
      levels, but not serum glucose levels 2h after the start of the meal tolerance
      test.

PMID- 27710823
TI  - Facile template-free fabrication of iron manganese bimetal oxides nanospheres
      with excellent capability for heavy metals removal.
AB  - Iron manganese bimetal oxides (IMBO) nanospheres were synthesized via a facile
      and environmentally friendly template-free approach. The obtained IMBO with large
      surface area and abundant surface functional groups exhibited excellent
      performance for heavy metals removal from aqueous solution, with the maximum
      adsorption capacities of As(V) and Cr(VI) were 132.77mg/g and 105.96mg/g,
      respectively. The adsorption mechanism study confirmed that except for
      electrostatic attraction, both surface hydroxyl group (OH-) and carbonate group
      (CO32-) simultaneously played a key role in the ion-exchange process with As(V)
      and Cr(VI) species, which finally formed inner-sphere surface complexes on the
      interface of IMBO. Furthermore, the remarkable removal of As(V) and Cr(VI) by
      fixed-bed column was also observed in the presence of various commonly competing
      anions, and the effective working capacities of IMBO for As(V) and Cr(VI) were
      approximately 410 pore volume (PV) and 320 pore volume (PV) when the breakthrough
      point was set at 10ppb. The exhausted IMBO could be easily regenerated by using a
      NaOH solution (0.1M). These results demonstrated that this IMBO was a potential
      and attractive adsorbent for the decontamination of arsenic/chromium polluted
      water system.

PMID- 27710824
TI  - Tobacco prevention and reduction with nursing students: A non-randomized
      controlled feasibility study.
AB  - BACKGROUND: Prevalence of tobacco use among nurses and nursing students is
      disproportionally high in Germany. However, from a public health perspective they
      are considered to be an important group for delivering smoking cessation
      interventions. As delivery of tobacco-related treatment depends on own smoking
      status, smoking prevention and cessation among the nursing professions is
      indicative for improving nurse and public health. OBJECTIVE: To evaluate the
      feasibility and effects of a comprehensive tobacco prevention and reduction
      program on psychosocial and environmental factors related to smoking behavior of
      nursing students. METHODS: Between 2014 and 2015, a non-randomized, controlled
      feasibility study was conducted in 12 schools of nursing with 397 nursing
      students in Germany. Students in the intervention group received a program
      (ASTRA) consisting of an introductory session, steering committee workshop,
      stress prevention lessons, evidence-based smoking cessation intervention, and
      action project. Six months after baseline assessment, change in smoking-related
      protective and risk factors was determined. Secondary endpoints included smoking
      behavior. RESULTS: The program was implemented in total in 5 of 7 intervention
      schools. About one third of smoking nursing students participated in a cessation
      intervention. The program seems to do better than a minimal intervention booklet
      in four primary outcomes: perceived descriptive, subjective, and injunctive norms
      towards smoking and nursing as well as perceived social support. As anticipated,
      there was no change in smoking behavior. CONCLUSIONS: The applied approach is
      feasible and able to improve important smoking-related norm perceptions of
      student nurses and perception of social support. However, additional context
      measures to influence the settings of nursing education currently rather
      supporting smoking seem to be necessary in order to promote smoking cessation
      among nursing students and to scale up implementation of the program.

PMID- 27710826
TI  - "A stressful and frightening experience"? Children's nurses' perceived readiness
      to care for children with cancer following pre-registration nurse education: A
      qualitative study.
AB  - BACKGROUND: In the UK children with cancer are cared for by children's nurses in
      a variety of settings, specialist and non-specialist. Whilst post-registration
      specialist education is available to some nurses, many nurses rely solely on pre
      registration education to competently care for these children. This study
      explores whether nurses perceive that this adequately prepares them. OBJECTIVES:
      To explore the extent to which qualified nurses perceive that pre-registration
      nurse education prepares them to care for children with cancer; to consider the
      implications for children's nursing pre-registration curricula. DESIGN: A small
      scale qualitative study was undertaken using an interpretivist approach. METHODS:
      Semi-structured interviews were conducted with six qualified children's nurses in
      two clinical areas - a specialist children's cancer inpatient ward, and a general
      children's ward where inpatients included children with cancer. RESULTS: Findings
      are discussed in relation to three emergent themes: Learning in Theory and
      Practice, Care of the Child and Family, and Resilience. Participants attached
      significance to the quantity and quality of practice experience. They reflected
      on barriers to specific and transferable theoretical learning and stressed the
      importance of integrating theory and practice. Understanding of family-centred
      care formed a significant part of their preparation. Preconceptions,
      communication with families and the emotional impact of this speciality were
      stressful. Improved pre-registration preparation may have developed participants'
      resilience. CONCLUSION: The complexities of caring for children with cancer and
      their families require well-prepared nurses. Participants' perceptions of
      preparedness were influenced by aspects of pre-registration education. Their
      experiences suggest that curricula should be practice-focused and include a range
      of placements. Specialist theoretical content must be integrated with practice
      and transferability of knowledge and skills made explicit. Reflection and problem
      based learning may foster coping mechanisms and resilience that will equip them
      to care for children with cancer.

PMID- 27710825
TI  - Assessing Learning Styles of Graduate Entry Nursing Students as a Classroom
      Research Activity: A quantitative research study.
AB  - BACKGROUND: A number of studies across different disciplines have investigated
      students' learning styles. Differences are known to exist between graduate and
      baccalaureate nursing students. However, few studies have investigated the
      learning styles of students in graduate entry nursing programs. . OBJECTIVES:
      Study objective was to describe graduate entry nursing students' learning styles.
      DESIGN/SETTING/PARTICIPANTS/METHODS: A descriptive design was used for this
      study. The Index of Learning Styles (ILS) was administered to 202 graduate entry
      nursing student volunteers at a southwestern university. Descriptive statistics,
      tests of association, reliability, and validity were performed. Graduate nursing
      students and faculty participated in data collection, analysis, and dissemination
      of the results. RESULTS: Predominant learning styles were: sensing - 82.7%,
      visual - 78.7%, sequential - 65.8%, and active - 59.9%. Inter-item reliabilities
      for the postulated subscales were: sensing/intuitive (alpha=0.70), visual/verbal
      (alpha=0.694), sequential/global (alpha=0.599), and active/reflective
      (alpha=0.572). Confirmatory factor analysis for results of validity were:
      chi2(896)=1110.25, p<0.001, CFI=0.779, TLI=0.766, WRMR=1.14, and RMSEA =0.034.
      CONCLUSIONS: Predominant learning styles described students as being concrete
      thinkers oriented toward facts (sensing); preferring pictures, diagrams, flow
      charts, demonstrations (visual); being linear thinkers (sequencing); and enjoying
      working in groups and trying things out (active),. The predominant learning
      styles suggest educators teach concepts through simulation, discussion, and
      application of knowledge. Multiple studies, including this one, provided similar
      psychometric results. Similar reliability and validity results for the ILS have
      been noted in previous studies and therefore provide sufficient evidence to use
      the ILS with graduate entry nursing students. This study provided faculty with
      numerous opportunities for actively engaging students in data collection,
      analysis, and dissemination of results.

PMID- 27710827
TI  - The importance of matching the evaluation population to the intervention
      population: Using Medicaid data to reach hard-to-reach intervention populations.
AB  - Subject recruitment is a challenge for researchers and evaluators, particularly
      with populations that are traditionally hard to reach and involve in research,
      such as low-income and minority groups. However, when the evaluation sample does
      not reflect a program's intended audience, the discrepancy may lead to evaluation
      results that are not valid for that audience. We conducted evaluation activities
      for a state Supplemental Nutrition Assistance Program-Education (SNAP-Ed)
      intervention that promotes consumption of fruits and vegetables (F&V) in low
      income areas. Previous program evaluations efforts had failed to obtain a
      sufficient proportion of individuals identified as low-income based on their
      participation in SNAP. We used state Medicaid data as a means of identifying low
      income families to recruit for a telephone survey (n=311) and an in-depth
      qualitative interview (n=30) that we designed for the program being evaluated. We
      chose to focus on the dynamics of parent-child communication around F&V because
      we considered this previously unevaluated component of the intervention vital to
      understanding program effectiveness. Our results indicated that the Medicaid
      database provided an appropriate sample and that parents reported frequent F&V
      requests from their children. Parents also reported that they would positively
      respond to requests in many different settings, such as grocery stores (92.6%),
      restaurants (88.1%), and fast food restaurants (80.4%).

PMID- 27710828
TI  - Biological and structural studies of phosphonium 'masked thiolate' compounds.
AB  - The ability of phosphonium cations to act as intracellular transport vectors is
      well-established. Phosphonioalkylthiosulfate zwitterions, and omega
      thioacetylalkylphosphonium salts, which act as 'masked thiolate' ligands, are
      useful precursors for the formation of phosphonium-functionalised gold
      nanoparticles, enabling the nanoparticles to be transported into cells for
      diagnostic and therapeutic purposes. In this study we have completed cytotoxicity
      studies of omega-thioacetylpropylphosphonium salts derived from
      triphenylphosphine and tri(4-fluorophenyl)phosphine, which show that the
      compounds are only toxic towards PC3 prostate cancer cells at high concentrations
      and at prolonged incubation periods and display IC50 values of 67 MUM and 252 MUM
      respectively, significantly higher than those of other phosphonium salts. MALDI
      TOF-MS has been used to investigate the uptake of the compounds by PC3 cells and
      to quantify detectable levels of the compounds inside the cells. The structures
      of omega-thioacetylpropyl(tri-4-fluorophenyl) phosphonium bromide and the
      corresponding tri(4-fluorophenyl)phosphoniopropylthiosulfate zwitterion have been
      investigated by single crystal X-ray crystallography. The results show that
      molecules of the zwitterion are held together through an extensive array of
      electrostatic and non-covalent interactions. The unit cell of omega
      thioacetylpropyl(tri-4-fluorophenyl)phosphonium bromide contains eight cations
      together with eight bromide anions and two waters of crystallisation, all held
      together through a complex network of hydrogen bonds. The differences in the
      molecular packing of the two compounds may account for the lower solubility of
      the zwitterion in aqueous solutions, compared with that of the phosphonium salt.

PMID- 27710829
TI  - Eliciting regret improves decision making at the end of life.
AB  - INTRODUCTION: Management choices at the end of life are high-stake decisions
      fraught with emotions, chief among is regret. Our objective in this paper is to
      test the utility of a regret-based model to facilitate referral to hospice care
      while helping patients clarify their preferences on how they wish to spend the
      remaining days of their lives. METHODS: A prospective cohort study that enrolled
      consecutive adult patients (n = 178) aware of the terminal nature of their
      disease. The patients were at the point in care where they had to decide between
      continuing potentially 'curative/life-prolonging' treatment (Rx) versus hospice
      care. Preferences were elicited using a Dual Visual Analog Scale regarding the
      level of regret of omission versus commission (RgO/RgC) towards hospice care and
      Rx. Each patient's RgO/RgC was contrasted against the predictive probability of
      death to suggest a management plan, which was then compared with the patient's
      actual choice. The probability of death was estimated using validated Palliative
      Performance Scale predictive model. RESULTS: Eighty-five percent (151/178) of
      patients agreed with the model's recommendations (p < 0.000001). Model predicted
      the actual choices for 72% (128/178) of patients (p < 0.00001). Logistic
      regression analysis showed that people who were initially inclined to be referred
      to hospice and were predicted to choose hospice over disease-directed treatment
      by the regret model have close to 98% probability of choosing hospice care at the
      end of their lives. No other factors (age, gender, race, educational status and
      pain level) affected their choice. CONCLUSIONS: Using regret to elicit choices in
      the end-of-life setting is both descriptively and prescriptively valid. People
      with terminal disease who are initially inclined to choose hospice and do not
      regret such a choice will select hospice care with high level of certainty.

PMID- 27710830
TI  - 6-C-(E-phenylethenyl)naringenin induces cell growth inhibition and cytoprotective
      autophagy in colon cancer cells.
AB  - 6-C-(E-phenylethenyl)naringenin (6-CEPN) is a small molecule found in naringenin
      fortified fried beef. It has been shown to suppress colon cancer cell
      proliferation, but the underlying mechanisms are not fully understood. Here we
      demonstrate that 6-CEPN suppresses tumour cell proliferation through cell cycle
      arrest in G1 phase, induces necrotic cell death and autophagy in colon cancer
      cells. Blockade of autophagy by knockdown of the essential autophagy proteins,
      Atg7 or beclin-1, resulted in aggravated cell death in response to 6-CEPN
      treatment. In addition, genome-wide transcriptome expression profiling by RNA
      sequencing revealed that 6-CEPN-mediated gene expression pattern was extremely
      similar to the transcriptome response induced by a RAS inhibitor salirasib
      (farnesylthiosalicylic acid [FTS; salirasib]). Subsequent molecular biological
      and biochemical experiments demonstrated that 6-CEPN indeed strongly inhibited
      RAS activation, leading to the inhibition of the downstream effector pathways c
      Raf/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase
      kinase and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin. More
      importantly, our computational molecular docking data showed that 6-CEPN could
      bind to the active site of isoprenylcysteine carboxyl methyltransferase (Icmt), a
      critical enzyme for the activation of RAS. Icmt activity assay showed that 6-CEPN
      inhibited its activity significantly. Knockdown of Icmt by siRNA attenuated 6
      CEPN-mediated autophagy and cell death. The present study demonstrates that 6
      CEPN induces cell growth inhibition and cytoprotective autophagy in colon cancer
      cells, at least in part, though inhibition of the Icmt/RAS signalling pathways.

PMID- 27710831
TI  - Change in surface roughness by dynamic shape-memory acrylate networks enhances
      osteoblast differentiation.
AB  - Microscale surface roughness has been shown to enhance osseointegration of
      titanium implants through increased osteoblast differentiation while osteoblast
      proliferation remains greater on smooth titanium. Taking advantage of these
      phenomena, we developed a shape memory (meth)acrylate copolymer with
      thermomechanical properties that created a time-dependent dynamic surface change
      from smooth to rough under in vitro cell culture conditions and evaluated the
      effect of the shape recovery on osteoblast response. Rough topographies were
      created using soft lithography techniques to mimic those found on clinically-used
      Ti surfaces (machined smooth; acid-etched; grit-blasted). The surface roughness
      was then reduced to smooth via compression and shown to fully recover within 24 h
      in culture conditions. When grown under static conditions, osteoblast number,
      alkaline phosphatase specific activity (ALP), and osteoprotegerin (OPG) and
      vascular endothelial growth factor (VEGF) production were unaffected by polymer
      surface roughness, but osteocalcin (OCN) was increased on the grit-blasted
      polymer mimic. Under dynamic conditions, DNA was reduced but OCN and OPG were
      increased on the compressed grit-blasted polymer at 3 days compared to static
      surfaces. The present study indicates that responses to polymer surface are
      sensitive to time-dependent changes in topography. The use of a shape memory
      polymer with dynamic surface roughness may improve osseointegration.

PMID- 27710833
TI  - CaCO3 nanoparticles as an ultra-sensitive tumor-pH-responsive nanoplatform
      enabling real-time drug release monitoring and cancer combination therapy.
AB  - The exploration of stimuli-responsive nano-theranostics provides powerful tools
      for simultaneously enhancing the accuracy and efficiency of cancer therapies.
      Herein, we develop mono-dispersed CaCO3 nanoparticles modified with polyethylene
      glycol (PEG) as a multifunctional nano-carrier for efficient loading of both Mn2+
      chelated chlorin e6 (Ce6(Mn)) as a photosensitizer, and doxorubicin (DOX) as a
      chemotherapy drug. Our CaCO3@Ce6(Mn)-PEG(DOX) nanoparticles, while being stable
      under physiological pH at 7.4, appear to be highly sensitive to reduced pH and
      would be rapidly degraded under slightly acidic environment, effectively
      releasing loaded therapeutic agents. Interestingly, owing to released Ce6(Mn),
      those nanoparticles show an interesting pH-dependent T1 signal enhancement under
      magnetic resonance (MR) imaging, which could be utilized for real-time monitoring
      of drug release. As discovered by MR and fluorescence imaging, intravenously
      (i.v.) injected CaCO3@Ce6(Mn)/DOX-PEG could gradually accumulate in the tumor,
      contributing to a superior synergistic anti-tumor effect in the combined
      photodynamic & chemotherapy. In conclusion, we have developed a tumor-pH
      activated nanocarrier based on biodegradable CaCO3 nanoparticles, which may be an
      ideal cancer theranostic nanoplatform with substantial potential for future
      clinical translation.

PMID- 27710832
TI  - Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium
      and heart-on-a-chip.
AB  - Engineering cardiac tissues and organ models remains a great challenge due to the
      hierarchical structure of the native myocardium. The need of integrating blood
      vessels brings additional complexity, limiting the available approaches that are
      suitable to produce integrated cardiovascular organoids. In this work we propose
      a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized
      myocardium. Enabled by the use of our composite bioink, endothelial cells
      directly bioprinted within microfibrous hydrogel scaffolds gradually migrated
      towards the peripheries of the microfibers to form a layer of confluent
      endothelium. Together with controlled anisotropy, this 3D endothelial bed was
      then seeded with cardiomyocytes to generate aligned myocardium capable of
      spontaneous and synchronous contraction. We further embedded the organoids into a
      specially designed microfluidic perfusion bioreactor to complete the
      endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity
      evaluation. Finally, we demonstrated that such a technique could be translated to
      human cardiomyocytes derived from induced pluripotent stem cells to construct
      endothelialized human myocardium. We believe that our method for generation of
      endothelialized organoids fabricated through an innovative 3D bioprinting
      technology may find widespread applications in regenerative medicine, drug
      screening, and potentially disease modeling.

PMID- 27710834
TI  - Application of chitosan microparticles for treatment of metritis and in vivo
      evaluation of broad spectrum antimicrobial activity in cow uteri.
AB  - Uterine disease such as metritis is associated with multiple bacterial infections
      in the uteri after parturition. However, treatment of metritis is challenging due
      to considerably high antibiotic treatment failure rate with unknown reason.
      Recently, chitosan microparticles (CM) have been developed to exert broad
      spectrum antimicrobial activity against bacterial pathogens, including multi-drug
      resistant bacteria, without raising CM resistant mutants. In this study, we
      tested, using metagenomics analysis, if CM maintain strong antimicrobial activity
      against pathogenic bacteria such as Fusobacteriaceae and Bacteroidaceae in cow
      uteri and evaluated CM's potency as an alternative antimicrobial agent to cure
      metritis in cows. Here, we report that efficacy of CM treatment for metritis was
      comparable to the antibiotic ceftiofur, and CM greatly altered uterine microflora
      of sick animals to healthy uterine microflora. Among uterine bacteria, CM
      significantly decreased Fusobacterium necrophorum, which is known pathogenic
      bacteria within the uterus. Taken together, we observed the broad spectrum
      antimicrobial activity of CM in vivo with an animal model, and further evaluated
      treatment efficacy in cows with metritis, providing insights into promising use
      of CM as an alternative antimicrobial agent for controlling uterine disease.

PMID- 27710835
TI  - Intolerance of uncertainty and post-traumatic stress symptoms: An investigation
      within a treatment seeking trauma-exposed sample.
AB  - BACKGROUND: Intolerance of uncertainty (IU) has been associated with post
      traumatic stress symptoms (PTSS) in the literature. However, no research to date
      has investigated the relationship between IU and PTSS within a clinical trauma
      exposed sample, which is an important next step in the literature and crucial for
      the generalizability of these findings. Therefore, the current study hypothesized
      that IU would be related to increased PTSS within a clinical sample of trauma
      exposed individuals. Further, we hypothesized that IU would be related to
      elevated PTSS after accounting for anxiety sensitivity (AS) and negative affect
      (NA), two known correlates of PTSS. Finally, we examined the relations between IU
      and the PTSS clusters (i.e., avoidance, emotional numbing, hyperarousal, and re
      experiencing) while covarying for AS and NA. METHODS: Participants included
      community adults (n=126) presenting at an outpatient clinic. All participants had
      previously experienced a traumatic event as defined by the DSM-5 PTSD Criterion
      A. METHODS: Results revealed that IU was significantly associated with increased
      PTSS above and beyond AS and NA. Further, results indicated that IU was
      significantly related to the avoidance, hyperarousal, and emotional numbing PTSS
      clusters, even after covarying for AS and NA. IU was not significantly associated
      with the PTSS re-experiencing cluster once AS and NA were taken into account.
      CONCLUSIONS: Our results expand upon the extant literature by demonstrating that
      IU is associated with PTSS above and beyond AS and NA within a clinical trauma
      exposed sample. These findings are discussed in terms of promising directions for
      future research and treatment strategies.

PMID- 27710836
TI  - Biologically-variable rhythmic auditory cues are superior to isochronous cues in
      fostering natural gait variability in Parkinson's disease.
AB  - INTRODUCTION: Rhythmic auditory cueing improves certain gait symptoms of
      Parkinson's disease (PD). Cues are typically stimuli or beats with a fixed inter
      beat interval. We show that isochronous cueing has an unwanted side-effect in
      that it exacerbates one of the motor symptoms characteristic of advanced PD.
      Whereas the parameters of the stride cycle of healthy walkers and early patients
      possess a persistent correlation in time, or long-range correlation (LRC),
      isochronous cueing renders stride-to-stride variability random. Random stride
      cycle variability is also associated with reduced gait stability and lack of
      flexibility. METHOD: To investigate how to prevent patients from acquiring a
      random stride cycle pattern, we tested rhythmic cueing which mimics the
      properties of variability found in healthy gait (biological variability). PD
      patients (n=19) and age-matched healthy participants (n=19) walked with three
      rhythmic cueing stimuli: isochronous, with random variability, and with
      biological variability (LRC). Synchronization was not instructed. RESULTS: The
      persistent correlation in gait was preserved only with stimuli with biological
      variability, equally for patients and controls (p's<0.05). In contrast, cueing
      with isochronous or randomly varying inter-stimulus/beat intervals removed the
      LRC in the stride cycle. Notably, the individual's tendency to synchronize steps
      with beats determined the amount of negative effects of isochronous and random
      cues (p's<0.05) but not the positive effect of biological variability.
      CONCLUSION: Stimulus variability and patients' propensity to synchronize play a
      critical role in fostering healthier gait dynamics during cueing. The beneficial
      effects of biological variability provide useful guidelines for improving
      existing cueing treatments.

PMID- 27710837
TI  - The influence of the aquatic environment on the control of postural sway.
AB  - Balance training in the aquatic environment is often used in rehabilitation
      practice to improve static and dynamic balance. Although aquatic therapy is
      widely used in clinical practice, we still lack evidence on how immersion in
      water actually impacts postural control. We examined how postural sway measured
      using centre of pressure and trunk acceleration parameters are influenced by the
      aquatic environment along with the effects of visual information. Our results
      suggest that the aquatic environment increases postural instability, measured by
      the centre of pressure parameters in the time-domain. The mean velocity and area
      were more significantly affected when individuals stood with eyes closed in the
      aquatic environment. In addition, a more forward posture was assumed in water
      with eyes closed in comparison to standing on land. In water, the low frequencies
      of sway were more dominant compared to standing on dry land. Trunk acceleration
      differed in water and dry land only for the larger upper trunk acceleration in
      mediolateral direction during standing in water. This finding shows that the
      study participants potentially resorted to using their upper trunk to compensate
      for postural instability in mediolateral direction. Only the lower trunk seemed
      to change acceleration pattern in anteroposterior and mediolateral directions
      when the eyes were closed, and it did so depending on the environment conditions.
      The increased postural instability and the change in postural control strategies
      that the aquatic environment offers may be a beneficial stimulus for improving
      balance control.

PMID- 27710838
TI  - BET bromodomain inhibition reduces maturation and enhances tolerogenic properties
      of human and mouse dendritic cells.
AB  - Transcription of inflammatory genes is tightly regulated by acetylation and
      deacetylation of histone tails. An inhibitor of the acetylated-lysine reader
      bromodomain and extra-terminal domain (BET) proteins, I-BET151, is known to
      counteract the induction of expression of inflammatory genes in macrophages. We
      have investigated the effects of I-BET151 on dendritic cell function, including
      expression of co-stimulatory molecules and cytokines, and capacity for T cell
      activation. Treatment of mouse bone marrow derived dendritic cells (BMDC) and
      human monocyte derived DCs (mdDC) with I-BET151 reduced LPS-induced expression of
      co-stimulatory molecules, as well as the production of multiple cyokines and
      chemokines. Most strikingly, secretion of IL-6, IL-12 and IL-10 was significantly
      reduced to 89.7%, 99.9% and 98.6% respectively of that produced by control cells.
      I-BET151-treated mdDC showed a reduced ability to stimulate proliferation of
      autologous Revaxis-specific T cells. Moreover, while I-BET151 treatment of BMDC
      did not affect their ability to polarise ovalbumin specific CD4+ CD62L+ naive T
      cells towards Th1, Th2, or Th17 phenotypes, an increase in Foxp3 expressing Tregs
      secreting higher IL-10 levels was observed. Suppression assays demonstrated that
      Tregs generated in response to I-BET151-treated BMDC displayed anti-proliferative
      capacity. Finally, evidence that I-BET151 treatment can ameliorate inflammation
      in vivo in a T cell dependent colitis model is shown. Overall, these results
      demonstrate marked effects of BET inhibition on DC maturation, reducing their
      capacity for pro-inflammatory cytokine secretion and T cell activation and
      enhancing the potential of DC to induce Foxp3 expressing Treg with suppressive
      properties.

PMID- 27710839
TI  - Environmental control of autoimmune inflammation in the central nervous system.
AB  - Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating
      disorder of the central nervous system (CNS), which causes severe disability and
      requires extensive medical attention and treatment. While the infiltration of
      pathogenic immune cells into the CNS leads to the formation of inflammatory
      lesions in its initial relapsing-remitting stage, late stages of MS are
      characterized by progressive neuronal loss and demyelination even without
      continued interaction with the peripheral immune compartment. Several genetic and
      environmental factors modulate and influence these processes on multiple levels.
      Genetic variants confer a predisposition for the development of MS, but are not
      accessible to therapeutic intervention as of today. However, migration studies
      suggest that environmental factors influence disease development, activity and
      progression. This article reviews mechanisms of disease pathogenesis in MS and
      their modulation by environmental factors such as geographical localization, the
      gut microbiome and the diet.

PMID- 27710840
TI  - Macrophages and dendritic cells in islets of Langerhans in diabetic autoimmunity:
      a lesson on cell interactions in a mini-organ.
AB  - Islets of Langerhans of all species harbor a small number of resident
      macrophages. These macrophages are found since birth, do not exchange with blood
      monocytes, and are maintained by a low level of replication. Under steady state
      conditions, the islet macrophages are in an activated state. Islet macrophages
      have an important homeostatic role in islet physiology. At the start of the
      autoimmune process in the NOD mouse, a small number of CD103+ dendritic cells
      (DC) are found at about the same time that CD4+ T cells also appear in islets. In
      the absence of the CD103+ DC in the Batf3 deficient mice, autoimmunity never
      develops. We discuss the interactions among the two phagocytes and beta cells
      that result in autoimmune diabetes in NOD mice.

PMID- 27710841
TI  - Removal naturally occurring radionuclides from drinking water using a filter
      specifically designed for Drinking Water Treatment Plants.
AB  - The occurrence of naturally occurring radionuclides in drinking water can pose
      health hazards in some populations, especially taking into account that routine
      procedures in Drinking Water Treatment Plants (DWTPs) are normally unable to
      remove them efficiently from drinking water. In fact, these procedures are
      practically transparent to them, and in particular to radium. In this paper, the
      characterization and capabilities of a patented filter designed to remove radium
      from drinking water with high efficiency is described. This filter is based on a
      sandwich structure of silica and green sand, with a natural high content
      manganese oxide. Both sands are authorized by Spanish authorities to be used in
      Drinking Water Treatment Plants. The Mn distribution in the green sand was found
      to be homogenous, thus providing a great number of adsorption sites for radium.
      Kinetic studies showed that the 226Ra adsorption on green sand was influenced by
      the content of major cations solved in the treated water, but the saturation
      level, about 96-99%, was not affected by it. The physico-chemical parameters of
      the treated water were unaltered by the filter. The efficiency of the filter for
      the removal of 226Ra remained unchanged with large water volumes passed through
      it, proving its potential use in DWTP. This filter was also able to remove
      initially the uranium content due to the presence of Fe2O3 particles in it,
      although it is saturated faster than radium.

PMID- 27710842
TI  - Allyl triphenyl phosphonium bromide based DES-functionalized carbon nanotubes for
      the removal of mercury from water.
AB  - Recently, deep eutectic solvents (DESs) have shown their new and interesting
      ability for chemistry through their involvement in variety of applications. This
      study introduces carbon nanotubes (CNTs) functionalized with DES as a novel
      adsorbent for Hg2+ from water. Allyl triphenyl phosphonium bromide (ATPB) was
      combined with glycerol as the hydrogen bond donor (HBD) to form DES, which can
      act as a novel CNTs functionalization agent. The novel adsorbent was
      characterized using Raman, FTIR, XRD, FESEM, EDX, BET surface area, TGA, TEM and
      Zeta potential. Response surface methodology was used to optimize the removal
      conditions for Hg2+. The optimum removal conditions were found to be pH 5.5,
      contact time 28 min, and an adsorbent dosage of 5 mg. Freundlich isotherm model
      described the adsorption isotherm of the novel adsorbent, and the maximum
      adsorption capacity obtained from the experimental data was 186.97 mg g-1. Pseudo
      second order kinetics describes the adsorption rate order.

PMID- 27710844
TI  - A geospatial analysis of soil lead concentrations around regional Oklahoma
      airports.
AB  - Lead has been banned from automobile gasoline since 1995; however, lead is still
      used as an additive to aviation gasoline (avgas). Airports are now one of the
      greatest sources of lead air emission in the US. The objectives of this study
      were (1) to evaluate soil lead levels radially from three regional airports; (2)
      collect historical meteorological data; (3) examine the soil organic matter
      content and (4) develop correlation coefficients to evaluate correlations among
      variables. Soil samples were collected from 3 different airports in Oklahoma and
      the soil lead concentration was measured using x-ray fluorescence (XRF). The
      measured soil lead concentrations were plotted with the corresponding GPS
      location in ArcGIS and Inverse Distance Weight spatial analysis was used to
      create modeled isopleths of soil lead concentrations. One of the three airports
      was found to have soil lead concentrations that correlate with soil organic
      matter with one other showing correlation between soil lead concentration and
      distance from the airport. The spatial modeled isopleths showed elevated soil
      lead concentrations in the direction of prevailing winds with "hot spots" near
      the avgas fueling stations.

PMID- 27710843
TI  - Identification of metabolites produced during the complete biodegradation of 1
      butyl-3-methylimidazolium chloride by an enriched activated sludge microbial
      community.
AB  - Ionic liquids (ILs) are highly polar solvents with unique physicochemical
      properties that make them promising green alternatives to volatile organic
      solvents. Since ILs can be toxic to organisms, the development of methods to
      degrade ILs into harmless molecules prior to disposal is critical to enhancing
      their green properties. In this study, metabolites generated during the
      biodegradation of 1-butyl-3-methylimidazolium chloride (BMIMCl) by an enriched,
      activated sludge microbial community were investigated. Biodegradation of BMIM
      and the metabolic products released into the growth media were examined using 1H
      NMR spectroscopy and mass spectrometry. To the best of our knowledge, this is the
      first reported complete primary catabolism of the biodegradation-resistant BMIMCl
      ionic liquid. The bacterial community responsible for degradation was analyzed
      using a 16S-rRNA amplicon approach. Although the community was diverse,
      Bacteroidetes was the predominant phylum. The study provides a greater insight
      into imidazolium-based IL biodegradability and a means to proactively prevent the
      ecotoxicity of the BMIM cation and its metabolites, by complete primary
      biodegradation of the cation and removal of most resulting metabolites, prior to
      release into aquatic waste streams.

PMID- 27710845
TI  - UV-initiated template copolymerization of AM and MAPTAC: Microblock structure,
      copolymerization mechanism, and flocculation performance.
AB  - Flocculation as the core technology of sludge pretreatment can improve the
      dewatering performance of sludge that enables to reduce the cost of sludge
      transportation and the subsequent disposal costs. Therefore, synthesis of high
      efficiency and economic flocculant is remarkably desired in this field. This
      study presents a cationic polyacrylamide (CPAM) flocculant with microblock
      structure synthesized through ultraviolet (UV)-initiated template
      copolymerization by using acrylamide (AM) and methacrylamido propyl trimethyl
      ammonium chloride (MAPTAC) as monomers, sodium polyacrylate (PAAS) as template,
      and 2,2'-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (VA-044) as
      photoinitiator. The microblock structure of the CPAM was observed through nuclear
      magnetic resonance (1H NMR and 13C NMR) spectroscopy, Fourier transform infrared
      (FTIR) spectroscopy, and scanning electron microscopy (SEM) analyses.
      Furthermore, thermogravimetric/differential scanning calorimetry (TG/DSC)
      analysis was used to evaluate its thermal decomposition property. The
      copolymerization mechanism was investigated through the determination of the
      binding constant MK and study on polymerization kinetics. Results showed that the
      copolymerization was conducted in accordance with the I (ZIP) template
      polymerization mechanism, and revealed the coexistence of bimolecular termination
      free-radical reaction and mono-radical termination in the polymerization process.
      Results of sludge dewatering tests indicated the superior flocculation
      performance of microblock flocculant than random distributed CPAM. The residual
      turbidity, filter cake moisture content, and specific resistance to filtration
      reached 9.37 NTU, 68.01%, and 6.24 (1012 m kg-1), respectively, at 40 mg L-1 of
      template poly(AM-MAPTAC) and pH 6.0. Furthermore, all flocculant except
      commercial CPAM showed a wide scope of pH application.

PMID- 27710847
TI  - Application of steel slag coated with sodium hydroxide to enhance precipitation
      coagulation for phosphorus removal.
AB  - Phosphorus removal has been studied for decades to reduce the environmental
      impact of phosphorus in natural waterbodies. Slag has been applied for the
      phosphorus removal by several mechanisms. In this study, sodium hydroxide coating
      was applied on the slag surface to enhance the efficiency of precipitation
      coagulation process. In the batch test, it was found that the capacity of the
      slag to maintain high pH decreases with increasing its exposure time to the
      aqueous solution. In the column test, the coarse-grained coated slag showed
      higher phosphorus removal efficiency than the fine-grained uncoated slag. The
      coated slag maintained pH higher than uncoated slag and, accordingly, the removal
      efficiency of phosphorus was higher. Especially, when pH was less than 8, the
      removal efficiency decreased significantly. However, coated slag provided an
      excess amount of aluminum and sodium. Thus, a return process to reuse aluminum
      and sodium as a coagulant was introduced. The return process yields longer
      lifespan of slag with higher phosphorus removal and lower concentration of
      cations in the effluent. With the return process, the phosphorus removal
      efficiency was kept higher than 60% until 150 bed volumes; meanwhile, the
      efficiency without return process became lower than 60% at 25 bed volumes.

PMID- 27710846
TI  - Heavy metals in intensive greenhouse vegetable production systems along Yellow
      Sea of China: Levels, transfer and health risk.
AB  - Recently, greenhouse vegetable production (GVP) has grown rapidly and counts a
      large proportion of vegetable production in China. In this study, the
      accumulation, health risk and threshold values of selected heavy metals were
      evaluated systematically. A total of 120 paired soil and vegetable samples were
      collected from three typical intensive GVP systems along the Yellow Sea of China.
      Mean concentrations of Cd, As, Hg, Pb, Cu and Zn in greenhouse soils were 0.21,
      7.12, 0.05, 19.81, 24.95 and 94.11 mg kg-1, respectively. Compared to rootstalk
      and fruit vegetables, leafy vegetables had relatively high concentrations and
      transfer factors of heavy metals. The accumulation of heavy metals in soils was
      affected by soil pH and soil organic matter. The calculated hazard quotients (HQ)
      of the heavy metals by vegetable consumption decreased in the order of leafy >
      rootstalk > fruit vegetables with hazard index (HI) values of 0.61, 0.33 and
      0.26, respectively. The HI values were all below 1, which indicates that there is
      a low risk of greenhouse vegetable consumption. Soil threshold values (STVs) of
      heavy metals in GVP system were established according to the health risk
      assessment. The relatively lower transfer factors of rootstalk and fruit
      vegetables and higher STVs suggest that these types of vegetables are more
      suitable for cultivation in greenhouse soils. This study will provide an useful
      reference for controlling heavy metals and developing sustainable GVP.

PMID- 27710848
TI  - Ecological effect and risk towards aquatic plants induced by perfluoroalkyl
      substances: Bridging natural to culturing flora.
AB  - In the present study, the concentrations and proportions of perfluoroalkyl
      substances (PFASs) in water and sediments (in different seasons) from the Qing
      River were investigated. The highest concentration of PFASs in water (207.59 ng L
      1) was found in summer. The composition of PFASs in water changed with time,
      perfluorobutane sulfonate (PFBS) was the predominant compound in spring and
      summer, while long-chain PFASs, perfluorooctanoic acid (PFOA) and perfluorooctane
      sulfonate (PFOS), started to increase in autumn and winter. The PFASs
      concentration in sediments ranged from 0.96 to 4.05 ng g-1 dw. The proportion of
      long-chain PFASs was higher than that of short-chain PFASs in sediments, the
      dominant component in sediments was PFOA with a contribution of 24.6-75.4% to
      total PFASs in sediments, followed by PFOS. The concentrations of PFASs in roots
      of emergent plants were relatively higher than those in submerged plants.
      However, the translocation effect of PFASs was not remarkable. Bioaccumulation
      factors (BAFs) of the aquatic plants indicated the absorption of PFASs were
      effective. BAFs in submerged plants basically increased with increasing chain
      length accordingly. In general, aquatic plants had the absorption preference for
      long-chain PFASs, especially PFOS, which was the predominant compounds in both
      submerged and emergent plants. Based on the results above, hornworts were
      selected to be cultivated indoor in the nutrient solution spiked gradient
      concentrations of PFOS to assess the general ecological risk. The results
      revealed that hornworts were resistant to PFOS and might be used as remediation
      flora to eliminate PFOS contamination.

PMID- 27710849
TI  - Scanning electrochemical microscopy based evaluation of influence of pH on
      bioelectrochemical activity of yeast cells - Saccharomyces cerevisiae.
AB  - In this research scanning electrochemical microscopy was applied for the
      investigation of immobilized yeast Saccharomyces cerevisiae cells. Two redox
      mediators based system was applied in order to increase the efficiency of charge
      transfer from yeast cells. 9,10-phenanthrenequinone (PQ) was applied as a
      lipophilic redox mediator, which has the ability to cross the cell's membrane;
      another redox mediator was ferricyanide, which acted as a hydrophylic electron
      acceptor able to transfer electrons from the PQ to the working electrode of SECM.
      Hill's function was applied to determine the optimal pH for this described SECM
      based system. The influence of pH on cell viability could be well described by
      Hill's function. It was determined that at pH 6.5 the PQ has a minimal toxic
      influence on yeast cells, and the kinetics of metabolic processes in cells as
      well as electron transfer rate achieved in consecutive action of both redox
      mediators were appropriate to achieve optimal current signals.

PMID- 27710850
TI  - Dynamics of nanoparticle diffusion and uptake in three-dimensional cell cultures.
AB  - This study aims at elucidating the effect of three-dimensional (3D) extracellular
      matrix on cell behaviour and nanoparticle (NP) diffusion and its consequences on
      NP cellular uptake mechansims. For this purpose, human dermal fibroblasts (HDF)
      and human fibrosarcoma (HT1080) cell lines were grown within a 3D collagen gel
      and exposed to model polystyrene (PS) NPs of controlled size (44 and 100nm).
      Results indicate that, in 3D, cell morphology dramatically changes compared to
      standard 2D cultures and NP diffusion within the matrix is hampered by the
      interaction with the collagen fibres. As a consequence, NP cellular uptake,
      modeled with equations describing the stoichiometric exchange between NPs and
      cell membrane, is significantly slowed down in 3D and in the case of 100 nm NPs,
      in part due to the hampered diffusion of NPs in collagen gel compared to their
      transport in standard cell culture medium. Furthermore, our outcomes point at a
      significant contribution of the cytoskeleton assembly, in particular actin
      microfilaments, in governing the uptake of PS NPs in a 3D environment, and also
      that the macropinocytosis process is preserved and is mainly involved in the
      internalization of PS NPs in a 3D environment. However, depending on cell type
      and nanoparticle size, other endocytic pathways are also implicated when moving
      from 2D to 3D culture systems. This work highlights the importance of studying
      the nano-bio interaction in experimental models that resembles in vivo conditions
      in order to better predict the therapeutic efficacy of drug delivery systems.

PMID- 27710851
TI  - Cancer mortality among adolescents and young adults: A historical cohort in a
      reference institution for cancer treatment in Santa Catarina/South of Brazil 2002
      2013.
AB  - OBJECTIVE: To identify factors associated with early mortality from cancer in
      adolescents and young adults in a reference institution for oncology treatment in
      Santa Catarina, Brazil. METHODS: We studied a retrospective cohort with an
      intentional sample of adolescents (ages 15-19) and young adults (ages 20-29)
      diagnosed with neoplasia. Secondary data were acquired from January 2002 to
      December 2013. Kaplan-Meier and Cox regression methods were used for survival
      analysis. Logistical analysis tested the association between early death (lower
      tertile between diagnosis and death, according to cancer type) and clinical or
      sociodemographic variables. RESULTS: We included a total of 889 cases with an
      average age of 23, with similar gender distributions and a predominance of
      Caucasian ethnicity. Using the Cox framework of proportional risks adjusted for
      neoplasia types and gender, individuals with non-hematological neoplasia (solid
      tumors) presented a 47% higher risk of dying when compared with individuals
      diagnosed with leukemias and lymphomas (HR: 1.47; 95%CI: 1.12-1.93). Chances of
      death were 31% higher for males than for females (HR: 1.31; 95%CI: 1.02-1.69).
      When adjusting for type of neoplasia and age (15-24 and 25-29) the risk of death
      by cancer was 51% greater in individuals diagnosed with non-hematological
      neoplasia when compared with individuals diagnosed with leukemias and lymphomas
      (HR: 1.51; 95%CI: 1.15-1.99). The chance of death by cancer in patients under the
      age of 25 was 33% greater when compared to that in older patients between the
      ages of 25 and 29 (HR: 1.33; 95%CI: 1.04-1.75). In multiple regression analysis,
      factors associated with early mortality from cancer were the number of years in
      school (P=0.011) and time between diagnosis and start of treatment (P<0.001).
      CONCLUSIONS: The sample studied with a longer period of time between diagnosis
      and the start of treatment (access to oncology therapy) and with fewer years in
      school showed that these factors had important roles in early death from cancer
      for the observed individuals. This must be considered when planning and
      identifying risk in young cancer patients in order to lower the impact of the
      disease on mortality for this age group.

PMID- 27710852
TI  - The association between maternal depression and sensitivity: Child-directed
      effects on parenting during infancy.
AB  - The current study prospectively explored infant behaviors as a moderator of the
      association between maternal depression and parenting sensitivity in a sample of
      167 families. Maternal depression was only associated with later sensitivity for
      infants who displayed more negativity during mother-infant interactions.

PMID- 27710853
TI  - Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and
      tubular cells: Implications for diabetic nephropathy.
AB  - Damage to renal tubular and mesangial cells is central to the development of
      diabetic nephropathy (DN), a complication of diabetes which can lead to renal
      failure. Mitochondria are the site of cellular respiration and produce energy in
      the form of ATP via oxidative phosphorylation, and mitochondrial dysfunction has
      been implicated in DN. Since the kidney is an organ with high bioenergetic needs,
      we postulated that hyperglycemia causes damage to renal mitochondria resulting in
      bioenergetic deficit. The bioenergetic profiles and the effect of hyperglycemia
      on cellular respiration of human primary mesangial (HMCs) and proximal tubular
      cells (HK-2) were compared in normoglycemic and hyperglycemic conditions using
      the seahorse bio-analyzer. In normoglycemia, HK-2 had significantly lower basal,
      ATP-linked and maximal respiration rates, and lower reserve capacity compared to
      HMCs. Hyperglycemia caused a down-regulation of all respiratory parameters within
      4 days in HK-2 but not in HMCs. After 8 days of hyperglycemia, down-regulation of
      respiratory parameters persisted in tubular cells with compensatory up-regulated
      glycolysis. HMCs had reduced maximal respiration and reserve capacity at 8 days,
      and by 12 days had compromised mitochondrial respiration despite which they did
      not enhance glycolysis. These data suggest that diabetes is likely to lead to a
      cellular deficit in ATP production in both cell types, although with different
      sensitivities, and this mechanism could significantly contribute to the cellular
      damage seen in the diabetic kidney. Prevention of diabetes induced damage to
      renal mitochondrial respiration may be a novel therapeutic approach for the
      prevention/treatment of DN.

PMID- 27710855
TI  - The valuable diagnosis of DIC and pre-DIC and prediction of a poor outcome by the
      evaluation of diagnostic criteria for DIC in patients with hematopoietic injury
      established by the Japanese Society of Thrombosis and Hemostasis.
AB  - OBJECTIVE: We evaluated the modified diagnostic criteria for disseminated
      intravascular coagulation (DIC), which was published by the Japanese Society of
      Thrombosis and Hemostasis (JSTH), in 274 suspected DIC patients with
      hematopoietic injury. MATERIALS AND METHODS: The diagnoses of the patients were
      as follows: DIC (n=125); pre-DIC (n=42) and non-DIC (n=107). The efficacy of the
      diagnostic criteria for DIC was evaluated using a receiver operating
      characteristic (ROC) analysis. RESULTS: The area under the curve (ARC) and odd's
      ratio for the global coagulation test (GCT) scores in the diagnosis of "DIC" were
      high, while those for the diagnosis of "DIC and pre-DIC" were low, suggesting
      that the addition of antithrombin (AT) and soluble fibrin (SF)/thrombin
      antithrobin complex (TAT) was required to diagnose "DIC and pre-DIC". Although
      the addition of the AT and SF/TAT values to the GCT did not increase its ability
      to predict a poor outcome, the JSTH's modified diagnostic criteria scores were
      correlated with the odds ratio for death. DISCUSSION AND CONCLUSION: The JSTH's
      modified diagnostic criteria for DIC, which included the GCT score, and the AT,
      and TAT/SF values, were useful for diagnosing DIC and pre-DIC, and predicting a
      poor outcome.

PMID- 27710854
TI  - Albendazole as a promising molecule for tumor control.
AB  - This work evaluated the antitumor effects of albendazole (ABZ) and its
      relationship with modulation of oxidative stress and induction of DNA damage. The
      present results showed that ABZ causes oxidative cleavage on calf-thymus DNA
      suggesting that this compound can break DNA. ABZ treatment decreased MCF-7 cell
      viability (EC50=44.9 for 24h) and inhibited MCF-7 colony formation (~67.5% at
      5MUM). Intracellular ROS levels increased with ABZ treatment (~123%). The
      antioxidant NAC is able to revert the cytotoxic effects, ROS generation and loss
      of mitochondrial membrane potential of MCF-7 cells treated with ABZ. Ehrlich
      carcinoma growth was inhibited (~32%) and survival time was elongated (~50%) in
      animals treated with ABZ. Oxidative biomarkers (TBARS and protein carbonyl
      levels) and activity of antioxidant enzymes (CAT, SOD and GR) increased, and
      reduced glutathione (GSH) was depleted in animals treated with ABZ, indicating an
      oxidative stress condition, leading to a DNA damage causing phosphorylation of
      histone H2A variant, H2AX, and triggering apoptosis signaling, which was
      confirmed by increasing Bax/Bcl-xL rate, p53 and Bax expression. We propose that
      ABZ induces oxidative stress promoting DNA fragmentation and triggering apoptosis
      and inducing cell death, making this drug a promising leader molecule for
      development of new antitumor drugs.

PMID- 27710856
TI  - Clinical and molecular epidemiology of factor XI deficiency in India.

PMID- 27710857
TI  - Cancer, other comorbidity, and risk of venous thromboembolism after stroke: a
      population-based cohort study.
AB  - INTRODUCTION: The impact of cancer and other comorbidity on the risk of venous
      thromboembolism (VTE) after stroke is poorly understood. METHODS: We used Danish
      population-based national databases to conduct a cohort study encompassing
      201,025 patients diagnosed with a first-time ischemic stroke, intracerebral
      hemorrhage, subarachnoid hemorrhage or unspecified stroke between 1995 and 2012.
      As a comparison cohort, 983,222 members of the general population were matched to
      the stroke patients by date of diagnosis, year of birth, sex, and specific
      comorbidities, using conditions in the Charlson Comorbidity Index and other VTE
      risk factors. We computed VTE cumulative risks, rates, and rate ratios. We
      examined the interaction with comorbidity, defined as the excess VTE rates not
      explained by stroke and comorbidity alone, for up to five years following stroke.
      RESULTS: Five-year VTE risks were 2.1% and 1.9% in the stroke and comparison
      cohorts, respectively. Three-month VTE rates peaked at a 5-fold increase (95%
      confidence interval [CI]: 4.4; 5.2) in stroke patients and remained 13% to 43%
      increased relative to the general population during subsequent follow-up. During
      the first three months after stroke, 15% to 33% of the VTE rates were
      attributable to the interaction between stroke and moderate (2-3) to high (>=4)
      comorbidity based on Charlson Comorbidity Index scores. Non-metastatic solid
      tumors and metastatic disease accounted for most observed interaction with
      stroke, representing 41% and 56% of attributable three-month VTE rates,
      respectively. No such interaction between comorbidity and stroke was observed
      during subsequent follow-up. CONCLUSIONS: Comorbidity, particularly cancer,
      increased the risk of VTE within three months following stroke.

PMID- 27710858
TI  - Novel FGB mutation Bbeta240Cys->Arg confirms importance of the Bbeta211-240
      disulphide for plasma expression of fibrinogen.

PMID- 27710859
TI  - Are subversion and conflict component parts of social cohesion?

PMID- 27710861
TI  - Novel indoline derivatives prevent inflammation and ulceration in dinitro-benzene
      sulfonic acid-induced colitis in rats.
AB  - BACKGROUND: In search of safer treatments for inflammatory bowel disease in
      subjects not responding to, or showing adverse effects to TNF-alpha antagonists,
      we tested three novel indoline carbamates in the 2,4-dinitrobenzene sulfonic acid
      (DNBS) model of colitis in rats. The compounds have anti-inflammatory activity in
      other disease models in mice. METHODS: AN827 (3-(2-(methoxy carbonyl) ethyl)
      indolin-4-ylethyl methyl) carbamate (0.1 or 1mg/kg), AN680 (3-(2-(methoxy
      carbonyl) ethyl) indolin-6-ylethyl methyl) carbamate (1.25 or 2.5mg/kg) and AN917
      (3-(3-amino propyl) indolin-4-ylethyl methyl) carbamate (1 or 2mg/kg), 5
      aminosalycilic acid (5-ASA) (1 or 100mg/kg) or saline (1ml/kg) were administered
      rectally 1h after intracolonic administration of DNBS, (35mg/kg in 30% alcohol).
      Disease severity was assessed four days after DNBS administration by change in
      body weight, colon weight, area of ulceration, myeloid peroxidase (MPO) activity,
      colonic TNF-alpha, IL-6 and IL-1beta levels. Histopathological scoring was
      performed after staining colon sections with hematoxylin and eosin and with
      antibodies to CD68 and CD11b. RESULTS: AN827 (0.1 and 1mg/kg), AN680 (2.5mg/kg)
      and AN917 (2.0mg/kg) significantly reduced all macroscopic and microscopic
      parameters of colitis, colonic pro-inflammatory cytokines, TNF-alpha, IL-1beta
      and IL-6 and MPO activity by about 80%. CONCLUSIONS: The indoline derivatives
      largely prevented the symptoms of colitis and were 500-50 times more potent and
      more effective than 5-ASA. It may be worth evaluating them in models of
      established colitis. Since AN827 is strongly bound by plasma proteins no adverse
      effects are expected if compound is absorbed into the circulation after rectal
      administration.

PMID- 27710862
TI  - Escitalopram affects spexin expression in the rat hypothalamus, hippocampus and
      striatum.
AB  - BACKGROUND: Spexin (SPX) is a recently discovered neuropeptide that exhibits a
      large spectrum of central and peripheral regulatory activity, especially when
      considered as a potent anorexigenic factor. It has already been proven that
      antidepressants, including selective serotonin reuptake inhibitors (SSRI), can
      modulate peptidergic signaling in various brain structures. Despite these
      findings, there is so far no information regarding the influence of treatment
      with the SSRI antidepressant escitalopram on brain SPX expression. METHODS: In
      this current study we measured SPX mRNA and protein expression in the selected
      brain structures (hypothalamus, hippocampus and striatum) of rats chronically
      treated with a 10mg/kg dose of escitalopram using quantitative Real-Time PCR and
      immunohistochemistry. RESULTS: Strikingly, long-term (4 week) drug treatment led
      to the downregulation of SPX expression in the rat hypothalamus. This supports
      the hypothesis that SPX may be involved in the hypothalamic serotonin-dependent
      actions of SSRI antidepressants and possibly also in the central mechanism of
      body mass increase. Conversely, SPX expression increased in the hippocampus and
      striatum. CONCLUSIONS: This is the first report of the effects of a
      neuropsychiatric medication on SPX expression in animal brain. Our findings shed
      a new light on the pharmacology of antidepressants and may contribute to a better
      understanding of the alternative mechanisms responsible for antidepressant
      action.

PMID- 27710860
TI  - Behavioral, morphometric, and gene expression effects in adult zebrafish (Danio
      rerio) embryonically exposed to PFOA, PFOS, and PFNA.
AB  - Perfluoroalkylated substances (PFAS) are a class of persistent anthropogenic
      chemicals that have been detected worldwide. PFASs consist of fluorinated carbon
      chains of varying length, terminal groups, and have a number of industrial uses.
      A previous zebrafish study from our laboratory showed that acute (3-120h post
      fertilization, 0.02-2.0MUM), waterborne embryonic exposure to these chemicals
      resulted in chemical specific alterations at 5days post fertilization (dpf), and
      some effects persisted up to 14 dpf. Using a gene battery consisting of 100
      transcripts identified several genes that were up or down regulated. This current
      study looks at the long-term impacts of PFASs in adult zebrafish using the same
      exposure regimen. It was hypothesized that sub-lethal exposure of perfluorooctane
      sulfonate (PFOS), perfluorononanoic acid (PFNA), or perfluorooctane sulfonate
      (PFOA) in embryonic zebrafish (3-120 hpf) would result in permanent morphometric,
      gene expression, and behavioral changes in adult fish similar to those observed
      at 5 and 14 dpf. Zebrafish were exposed to PFOS, PFOA, and PFNA (Control 0MUM,
      2.0MUM) for the first five days post fertilization. At six months post
      fertilization, no PFAS treatment resulted in a significant change in total body
      length or weight. In terms of behavior, PFNA males showed a reduction in total
      distance traveled and time of immobility, and an increase in thigmotaxis
      behavior, aggressive attacks, and preference for the bright section of the tank.
      PFOS treated males had a reduced aggression behavior, and PFOA females preferred
      the dark section of the tank. Gene expression of slco2b1, slco1d1, and tgfb1a
      were analyzed because these transcripts were previously found to be affected by
      PFAS exposure in 5dpf and 14 dpf zebrafish and resulted in: significant decrease
      in expression of slco2b1 for both sexes in PFNA and PFOS treated groups,
      significant decrease of slco1d1 in all treatment groups for females and PFOS and
      PFOA exposed males, significant increase of tgfb1a in males treated with PFOS and
      PFNA, and a significant increase of bdnf in all PFAS male groups. This study
      demonstrates that acute, embryonic exposure (5days) to individual PFASs result in
      significant biochemical and behavioral changes in young adult zebrafish 6 months
      after exposure. These three PFASs have long term and persistent impacts following
      short term embryonic exposure that persists into adulthood.

PMID- 27710863
TI  - Expression of Alzheimer's disease risk genes in ischemic brain degeneration.
AB  - We review the Alzheimer-related expression of genes following brain ischemia as
      risk factors for late-onset of sporadic Alzheimer's disease and their role in
      Alzheimer's disease ischemia-reperfusion pathogenesis. More recent advances in
      understanding ischemic etiology of Alzheimer's disease have revealed
      dysregulation of Alzheimer-associated genes including amyloid protein precursor,
      beta-secretase, presenilin 1 and 2, autophagy, mitophagy and apoptosis. We review
      the relationship between these genes dysregulated by brain ischemia and the
      cellular and neuropathological characteristics of Alzheimer's disease. Here we
      summarize the latest studies supporting the theory that Alzheimer-related genes
      play an important role in ischemic brain injury and that ischemia is a needful
      and leading supplier to the onset and progression of sporadic Alzheimer's
      disease. Although the exact molecular mechanisms of ischemic dependent
      neurodegenerative disease and neuronal susceptibility finally are unknown, a
      downregulated expression of neuronal defense genes like alfa-secretase in the
      ischemic brain makes the neurons less able to resist injury. The recent challenge
      is to find ways to raise the adaptive reserve of the brain to overcome such
      ischemic-associated deficits and support and/or promote neuronal survival.
      Understanding the mechanisms underlying the association of these genes with risk
      for Alzheimer's disease will provide the most meaningful targets for therapeutic
      development to date.

PMID- 27710864
TI  - The effects of hydrogen sulfide on electrical field stimulation-induced
      neurogenic contractile responses in isolated rabbit lower esophageal sphincter:
      Contribution of nitrergic and non-adrenergic non-cholinergic transmission.
AB  - BACKGROUND: Hydrogen sulfide (H2S) is a gaseous signaling molecule that, similar
      to nitric oxide (NO), plays an important role as an inhibitor neurotransmitter in
      the digestive tract. This study aimed to investigate the effect of H2S and to
      identify neurogenic contraction responses dependent on the electrical field
      stimulation (EFS) in the isolated lower esophageal sphincters of rabbits.
      METHODS: An isolated lower esophageal sphincter was placed in an organ bath
      system and mechanical responses were recorded using a force transducer. The nerve
      evoked contractile responses were obtained by EFS. The contractile responses were
      obtained as biphasic "on" and "off" phases seen at the beginning and end of EFS,
      respectively. RESULTS: Sodium hydrogen sulfide (NaHS) reduced the EFS-mediated
      "off" phase and the EFS-mediated non-adrenergic non-cholinergic (NANC) "off"
      phase. NaHS reduced the EFS-mediated "on" phase as well. l-Cysteine reduced the
      EFS-mediated "off" phase and the EFS-mediated NANC "off" phase. l
      Propargylglycine (PAG) did not affect the EFS-mediated "off" phase or the EFS
      mediated NANC "off" phase. NaHS, l-cysteine, and PAG reduced the EFS-mediated, NO
      independent "off" phase. The effect of NaHS in all of the experiments returned in
      time. Also, NaHS caused significant relaxation of 80-mM KCl-Krebs solution
      induced-contractions, while l-cysteine and PAG did not cause a significant
      relaxation. CONCLUSION: These findings suggest that H2S has an inhibitory effect
      on the lower esophageal sphincter muscle. While the effect of H2S on EFS-mediated
      responses disappeared in time, the effect of H2S sustained the KCl-Krebs solution
      induced contractions. This shows that H2S may have an effect on neurotransmission
      at the nerve terminal.

PMID- 27710865
TI  - Hydrocortisone and dexamethasone dose-dependently stabilize mast cells derived
      from rat peritoneum.
AB  - BACKGROUND: Besides their anti-inflammatory properties, corticosteroid drugs
      exert anti-allergic effects. Exocytosis of mast cells is electrophysiologically
      detected as the increase in the whole-cell membrane capacitance (Cm). Therefore,
      the lack of such increase after exposure to the drugs suggests their mast cell
      stabilizing effects. METHODS: We examined the effects of 1, 10, 100 and 200MUM
      hydrocortisone or dexamethasone on the degranulation from rat peritoneal mast
      cells. Employing the whole-cell patch-clamp recording technique, we also tested
      their effects on the Cm during exocytosis. RESULTS: At relatively lower
      concentrations (1, 10MUM), both hydrocortisone and dexamethasone did not
      significantly affect the degranulation from mast cells and the increase in the Cm
      induced by GTP-gamma-S. Nevertheless, at higher doses (100, 200MUM), these drugs
      inhibited the degranulation from mast cells and markedly suppressed the GTP-gamma
      S-induced increase in the Cm. CONCLUSIONS: Our results provided
      electrophysiological evidence for the first time that corticosteroid drugs, such
      as hydrocortisone and dexamethasone, inhibited the exocytotic process of mast
      cells in a dose-dependent manner. The mast cell-stabilizing effects of these
      drugs may be attributable to their "non-genomic" action, by which they exert
      rapid anti-allergic effects.

PMID- 27710866
TI  - Identification and functional characterization of HbOsmotin from Hevea
      brasiliensis.
AB  - Latex in the laticiferous cell network of Hevea brasiliensis tree is composed of
      cytoplasm that synthesizes natural rubber. Ethylene stimulation of the tree bark
      enhances latex production partly by prolonging the duration of latex flow during
      the tapping process. Here, we identified an osmotin-like cDNA sequence
      (HbOsmotin) from H. brasiliensis that belongs to the pathogenesis-related 5 (PR
      5) gene family. The HbOsmotin protein is present in the lutoids of latex in H.
      brasiliensis, whereas in onion epidermal cells, this protein is predominantly
      distributed around the cell wall, suggesting that it may be secreted from the
      cytoplasm. We investigated the effects of exogenous ethylene on HbOsmotin
      transcription and protein accumulation in rubber latex, and further determined
      the protein function after osmotic stress in Arabidopsis. In regularly tapped
      trees, HbOsmotin expression was drastically inhibited in rubber latex after
      tapping, although the expression was subsequently recovered by ethylene
      stimulation. However, in virgin plants that had never been tapped, exogenous
      ethylene application slightly decreased HbOsmotin expression. HbOsmotin
      overexpression in Arabidopsis showed that HbOsmotin reduced the osmotic stress
      tolerance of the plant, which likely occurred by raising the water potential.
      These data indicated that HbOsmotin may contribute to osmotic regulation in
      laticiferous cells.

PMID- 27710867
TI  - Highlighting the microbial diversity of 12 French cheese varieties.
AB  - Surface-ripened cheeses host complex microbial communities responsible for the
      transformation of milk into cheese as well as the development of important
      properties in terms of texture, color and sensory perception. In this study, we
      used high-throughput amplicon sequencing to decipher the bacterial and fungal
      diversity of 60 cheeses belonging to 12 popular French cheese varieties. Using
      this approach, 76 bacterial and 44 fungal phylotypes were identified. Major
      differences were observed between rind and core samples and also according to
      cheese varieties and manufacturing processes. Occurrence analysis revealed the
      presence of widespread taxa as well as operational taxonomic units (OTUs)
      specific to one or several cheese varieties. Finally, we observed patterns
      specific to the cheese production facility, supporting the importance of
      indigenous microorganisms for the microbial assemblage of cheese microbiota.

PMID- 27710868
TI  - Efficacy and tolerability of brivaracetam compared to lacosamide, eslicarbazepine
      acetate, and perampanel as adjunctive treatments in uncontrolled focal epilepsy:
      Results of an indirect comparison meta-analysis of RCTs.
AB  - BACKGROUND: Brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM),
      and perampanel (PER) have been recently marketed as adjunctive treatments for
      focal onset seizures. To date, no randomized controlled trial (RCT) has directly
      compared BRV with ESL, LCM, or PER. PURPOSE: To compare BRV with the other add-on
      AEDs in patients with uncontrolled focal epilepsy, estimating their efficacy and
      tolerability through an adjusted, common-reference based indirect comparison meta
      analysis. METHODS: We systematically searched RCTs in which add-on treatment with
      ESL or LCM in patients with focal onset seizures have been compared with placebo.
      Efficacy and tolerability outcomes were considered. Random-effects Mantel
      Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the
      efficacy of BRV, LCM, ESL, or PER versus placebo. Adjusted indirect comparisons
      were then made between BRV and the other three AEDs using the obtained results,
      comparing the minimum and the highest effective recommended daily dose of each
      drug. RESULTS: Seventeen RCTs, with a total of 4971 patients were included. After
      adjusting for dose-effects, indirect comparisons showed no difference between BRV
      and LCM, ESL, or PER for responder rate and seizure freedom. Lower adverse events
      were observed with high dose BRV compared to high dose ESL or PER, but no
      difference was found in withdrawing because of adverse events. CONCLUSIONS:
      Indirect comparisons do not demonstrate a significant difference in efficacy
      between add-on BRV and LCM, ESL, or PER in focal epilepsy, and might suggest a
      better tolerability of BRV than ESL, and possibly also PER, at the highest
      effective recommended dose.

PMID- 27710869
TI  - Plasma proteomics in CML patients before and after initiation of tyrosine kinase
      inhibitor therapy reveals induced Th1 immunity and loss of angiogenic stimuli.
AB  - BACKGROUND AND AIMS: The simultaneous measurement of many proteins is now
      possible using multiplex assays. In this pilot study we investigated a total of
      124 proteins in plasma from chronic myeloid leukemia (CML) patients with the
      purpose of identifying proteins that are differently expressed at diagnosis and
      after tyrosine kinase inhibitor (TKI) treatment initiation. METHODS: Samples were
      taken from 14 CML patients at diagnosis and after three months of TKI treatment
      (imatinib or dasatinib). Samples were analyzed by Mesoscale Discovery, Myriad RBM
      MAP technology and Olink Proseek. RESULTS: Multiple plasma proteins were
      differentially expressed before and after initiation of TKI therapy. Protein
      patterns demonstrated a possible shift towards Th1-immunity and reduced
      angiogenic stimuli. Further, some plasma proteins were identified that can be of
      potential interest to study further for biologic, prognostic or therapeutic
      significance such as E-selectin, uPAR, growth hormone and carbonic anhydrase IX.
      CONCLUSIONS: Plasma proteomics seems feasible and useful in CML patients, both
      for studying patterns of protein expression and for identifying single proteins
      differentially expressed before and after treatment. Plasma proteomics may be
      useful to map disease activity and biological processes. Hence, plasma proteomics
      can be used to understand drug mechanisms and treatment responses in CML.

PMID- 27710870
TI  - Individuals with high obsessive-compulsive tendencies or undermined confidence
      rely more on external proxies to access their internal states.
AB  - BACKGROUND AND OBJECTIVES: The Seeking Proxies for Internal States (SPIS)
      hypothesis predicts that obsessive-compulsive disorder (OCD) is associated with a
      deficit in subjective convictions, which may lead to a reliance on external
      substitutes for the perceptions of an individual's internal states. Two well
      designed studies were performed for the present work that adopted a false bio
      feedback procedure in a muscle tension task to examine the SPIS hypothesis.
      METHODS: The false bio-feedback paradigm was used to investigate our hypothesis.
      NeXus-10 Mark II hardware and V2011 BioTrace + software (Mind Media B.V., Herten,
      Netherlands) were utilized to measure the muscle tension of the flexor
      carpiulnaris muscle, which characterized the target's internal state. In
      addition, false EMG changes were recorded and displayed on a computer monitor and
      were considered external proxies. RESULTS: Study 1 demonstrated that the
      participants with high obsessive-compulsive (OC) tendencies were more affected by
      the false bio-feedback and exhibited lower confidence in their judgments
      regarding their muscle tension compared with the participants with low OC
      tendencies. These findings indicate that subjects with high OC tendencies were
      more influenced by self-perception effects. In contrast, the subjects in the
      undermined confidence group in Study 2 were more easily influenced by the false
      bio-feedback compared with the control group, which suggests that the subjects in
      the undermined confidence group were more affected by self-perception effects.
      LIMITATIONS: We did not combine the undermined confidence with OC tendencies or
      OCD symptoms in our paradigm to investigate their joint effects on self
      perception. CONCLUSIONS: Our findings provide further evidence that supports the
      SPIS hypothesis, which indicates that OC tendencies and the confidence in an
      individual's recognition of internal states appear to have similar effects on the
      assessment of internal states and reliance on proxies.

PMID- 27710871
TI  - Trabectedin as a chemotherapy option for patients with BRCA deficiency.
AB  - Trabectedin is a marine-derived product that was originally isolated from the
      Caribbean sea squirt Ecteinascidia turbinata and the first anticancer marine drug
      to be approved by the European Union. It is currently used as a single agent for
      the treatment of patients with soft tissue sarcoma after failure of
      anthracyclines and ifosfamide, or for those patients who are unsuited to receive
      these agents, and in patients with relapsed, platinum-sensitive ovarian cancer in
      combination with pegylated liposomal doxorubicin. Trabectedin has a unique multi
      faceted mechanism of action that involves transcription regulation and DNA repair
      systems, including transcription-coupled nucleotide excision repair and
      homologous recombination repair (HRR) as the main hallmarks of its
      antiproliferative activity. In addition, trabectedin has shown the ability to
      modulate the tumor microenvironment. Indeed, the activity of trabectedin is
      related to altered function and expression of DNA repair genes, such as BRCA1
      (BReast-CAncer susceptibility gene 1) and BRCA2. The particular sensitivity of
      sarcoma, ovarian and breast cancer cells deficient in HRR, previously observed in
      preclinical models, now has been confirmed in the clinical setting as well,
      suggesting that BRCA mutations are associated with improved clinical responses to
      trabectedin. Current efforts are focused on the evaluation of these unique
      features of trabectedin and on the identification of predictive factors for
      patients with an objective to determine whether a deficiency of HRR DNA repair
      pathway could impact the clinical benefit achieved from trabectedin.

PMID- 27710872
TI  - Pharmacological evaluation of poly(3-methylthiophene) and its
      titanium(IV)phosphate nanocomposite: DNA interaction, molecular docking, and
      cytotoxic activity.
AB  - Cancer and pathogenic microbial diseases have terribly affected human health over
      a longer period of time. In response to the increasing casualties due to cancer
      and microbial diseases, unique poly(3-methylthiophene) and poly(3
      methylthiophene)-titanium(IV)phosphate composite were prepared via in-situ
      oxidative chemical polymerization in this work. The poly(3-methylthiophene) and
      poly(3-methylthiophene)-titanium(IV)phosphate composite were well characterized
      by Fourier transform infrared spectroscopy and field emission scanning electron
      microscopy. DNA binding studies by UV-Visible and fluorescence spectroscopic
      investigations indicated strong binding affinities of poly(3-methylthiophene) and
      poly(3-methylthiophene)-titanium(IV)phosphate nanocomposite; leading to
      structural damage of DNA. Poly(3-methylthiophene)-titanium(IV)phosphate
      nanocomposite showed stronger interactions with DNA as compared to poly(3
      methylthiophene) and from dye displacement assay it was confirmed that mode of
      binding of both the formulations was intercalative. The antimicrobial screening
      revealed that polymer and its composite displayed stronger antibacterial effects
      than ampicillin against Bacillus subtilis, Staphylococcus aureus, Pseudomonas
      aeruginosa and Salmonella typhimurium. Besides, the poly(3-methylthiophene) and
      poly(3-methylthiophene)-titanium(IV)phosphate nanocomposite showed dose dependent
      effects towards estrogen receptor positive breast cancer (MCF-7) and estrogen
      receptor negative breast cancer (MDA-MB-231) cell lines; with poly(3
      methylthiophene)-titanium(IV)phosphate nanocomposite showing better activities
      against both cell lines. In all in-vitro biological investigations, poly(3
      methylthiophene)-titanium(IV)phosphate composite showed superior properties to
      that of the pure poly(3-methylthiophene), which encouraged us to suggest its
      potential as future therapeutic gear in drug delivery and other allied fields.

PMID- 27710873
TI  - Short-range ultraviolet irradiation with LED device effectively increases serum
      levels of 25(OH)D.
AB  - Impairment of the activities of daily living (ADL) by osteoporosis is an
      important concern in developed countries with a super-aging population. Vitamin
      D, which is a crucial molecule in bone metabolism and mainly produced
      endogenously with ultraviolet (UV) light exposure, is known to be insufficient in
      the elderly population. We used an UV Light-Emitting Diode (UV-LED) instrument
      generating a narrow-range wavelength to analyze the efficacy of endogenous
      vitamin D production. The primary purpose of this study was to examine the
      effects of UV irradiation at various narrow-range wavelengths using UV-LED on
      vitamin D supplementation. The second one was to clarify the short-term effects
      of UV irradiation on bone morphology in mice. Vitamin D-starved C57BL/6 female
      mice (n=7 per group) were UV-irradiated (268nm, 282nm, 290nm, 305nm, and 316nm)
      with 1kJ/m2 twice a week for 4weeks. UV irradiation using UV-LED had significant
      effects on increasing serum 25(OH)D levels in all wavelength groups (P<0.001, all
      groups) as compared to a control group. Among irradiated groups, wavelength of
      316nm had a less marked effect on 25(OH)D production compared with other
      wavelengths at 1week of UV irradiation (P<0.05). Levels of 1,25(OH)2D were
      significantly increased after 4weeks irradiation with UV-B or UV-C irradiation
      (P<0.05). mRNA levels of vitamin D 25-hydroxylase were increased with UV-B or UV
      C irradiation (268nm-305nm), significantly. Micro-CT examination revealed that
      short-term (4weeks) UV-irradiation did not induce morphological change of mice in
      any group. This study provides essential information that narrow-range UV
      irradiation with LED can increase the endogenous production of vitamin D, and
      mRNA levels of the responsible enzyme. Although bone morphology was not altered
      by short-term UV irradiation in this study, an increase of serum vitamin D might
      improve bone morphology with long-term irradiation.

PMID- 27710874
TI  - Hyperfuctioning insular thyroid carcinoma: A rare case report.
AB  - INTRODUCTION: Insular carcinoma of thyroid (ICT) is a rare pattern of thyroid
      tumor. Being hyperfunctioning makes the condition rarer. Here we reported a case
      of ICT associated with hyperthyroidism. CASE REPORT: A 65-year-old female
      presented with neck mass for 4 years. She had symptoms of thyrotoxicosis and
      received antithyroid treatment. She was referred for surgical management. She had
      multiple, non tender, mobile masses in the neck. Ultrasound showed midline
      multiple heterogenous mass lesions with multiple lymph nodes in right side of the
      neck largest one measuring 2*2cm. The patient was prepared for total thyrodectomy
      with radical neck dissection. The result of histopathology confirmed unifocal,
      poorly differentiated ICT. The post operative course was uneventful. CONCLUSION:
      Insular carcinoma is a rare disease. It may present with long history of signs
      and symptoms of hyperthyroidism. Total thyroidectomy is the main line of
      treatment.

PMID- 27710875
TI  - Biventricular transient systolic dysfunction after mitral valve replacement:
      Pericardial decompression syndrome.
AB  - BACKGROUND: Pericardial decompression syndrome is defined as paradoxical
      hemodynamic instability, left ventricular or bi ventricular systolic dysfunction
      and pulmonary edema after pericardial fluid drainage. Pericardial Decompression
      Syndrome is an unexpected clinical scenario with an incidence less than 5% in all
      surgically or percutaneously managed pericardial tamponade patients. The aim of
      this manuscript was to describe a case with cardiac tamponade in whom acute
      biventricular heart failure and pulmonary edema developed after surgical creation
      of a pericardial window, and to discuss this case in light of the literature.
      CASE REPORT: A 43-year-old woman who underwent mitral valve replacement three
      weeks ago admitted to our hospital with dyspnea, tachycardia, and atrial
      fibrillation. Large quantity of pericardial fluid (35mm in the posterior wall,
      25mm in the anterior wall) with partial compression of the right ventricle and
      50% left ventricle ejection fraction (LVEF) was determined via transthoracic
      echocardiography (TTE). After creation of pericardio-pleural window, more than
      1000ml of serosanguineous fluid were quickly removed from the pericardial space.
      During the following hours of the decompression, the patient's condition
      deteriorated and overt pulmonary edema developed. On the second day,
      biventricular systolic dysfunction, global diffuse hypokinesia and 15-20% LVEF
      was observed via TTE. High-dose inotropic support and diuretics was continued.
      During follow up she was progressively weaned off inotropes, LVEF were raised to
      35%. Two weeks later, repeated TTE showed normal biventricular systolic function
      and LVEF was 50%. CONCLUSION: We recommend gradual removal of pericardial
      effusion under hemodynamic monitoring, especially in patient with postcardiotomy
      tamponade.

PMID- 27710876
TI  - Bilateral simultaneous VATS for complete resection of bilateral posterior
      mediastinal bronchogenic cyst: A case report.
AB  - INTRODUCTION: The mediastinal bronchogenic cysts represents 50%-60% of
      mediastinal cysts and rarely occurs in the posterior mediastinum. The final
      surgical resection is indicated for symptomatic patients and is recommended for
      some asymptomatic patients in order to establish the diagnosis and to avoid any
      subsequent complications. CASE PRESENTATION: We report a case of 17 years-old
      male suffering from bronchogenic cysts of the mediastinum. The patient was
      admitted to our hospital complaining with dry chough and dyspnea; CT scan showed
      a cystic mass in posterior mediastinum. To achieve a correct diagnosis and to
      prevent the risk of complications, a complete surgical resection was performed by
      using bilateral simultaneous VATS. DISCUSSION: Bronchogenic cysts manifest as
      solitary or multiple lesions, majority of which are located in the mediastinum
      while sometimes can occur in the lung parenchyma. They are usually asymptomatic
      and casually discovered at chest X-ray or CT scan. The most common complications
      are infections, pneumothorax and hemoptysis. The complete surgical resection is
      the only radical and definitive treatment of the bronchogenic mediastinal cysts.
      VATS permits good exposure of the thoracic cavity including the mediastinum and
      better evaluation of the anatomic relationship. The absence of intra and
      postoperative complications, the reduction of pain in the early postoperative
      period demonstrate the security of this approach. CONCLUSION: Bilateral
      simultaneous VATS for resection of bilateral posterior mediastinal bronchogenic
      cyst may be a useful approach. In our case no intra and post-operative
      complications occurred and patient discharged home on 4 rd day.

PMID- 27710877
TI  - Ophthalmologic evaluation in geriatric patients: Assessment of consistency
      between patients' complaints and ocular diagnoses.
AB  - PURPOSE: This study aimed to assess the consistency between patients' complaints
      and their eye diseases. DESIGN: Cross-sectional study. METHODS: RESULTS: The
      frequencies of at least one newly diagnosed visually important ocular disease
      were 25.9%, 27.0%, and 45.3% in groups 1, 2, and 3, respectively (p<0.001). The
      same frequencies were significantly higher in patients >75 years of age compared
      with the younger group (59.1% vs. 22.0%, p<0.001). Although these values were
      statistically significant in patients <=75 years of age (p<0.001), they were
      insignificant in patients >75 years of age according to type of complaints
      (p=0.773). Patients with diabetes mellitus exhibited significantly lower vision,
      higher rate of visually important ocular diseases, and higher intraocular
      pressure readings than patients without diabetes mellitus (p=0.009, 0.015, and
      0.002, respectively). CONCLUSIONS: Visually important ocular diseases were
      diagnosed approximately in a quarter of patients who had no complaints about
      decrease in vision and in more than half of the oldest geriatric patients
      (>75years) irrespective of the type of complaints.

PMID- 27710878
TI  - How effective is the ketogenic diet for electrical status epilepticus of sleep?
AB  - Electrical status epilepticus of sleep (ESES), with the activation of profuse
      amounts of epileptiform discharges in sleep, may lead to intractable epilepsy and
      neurocognitive decline in children. Numerous varied treatments including
      antiseizure medications, steroids, and surgery have been investigated as possible
      treatment options. The ketogenic diet (KD) is an additional treatment option
      which may add to our treatment armamentarium for ESES. The KD may theoretically
      improve ESES by affecting GABA systems and reducing inflammation. Clinical
      reports of the KD for ESES have been heterogeneous, but to date 38 children have
      been described in six publications. Overall, 53% had EEG improvement, 41% had>50%
      seizure reduction, 45% had cognitive improvement, but only 9% had EEG
      normalization. This review will assess the efficacy of the KD in the treatment of
      ESES based on known data as well as possible mechanisms of action and the need
      for future study.

PMID- 27710879
TI  - Immunoregulatory effects of necroptosis in bacterial infections.

PMID- 27710880
TI  - Mercury and methylmercury distribution in the intertidal surface sediment of a
      heavily anthrophogenically impacted saltwater-mangrove-sediment interplay zone.
AB  - Total mercury (THg) and methylmercury (MeHg) concentrations were determined from
      sediment samples collected from thirty sampling stations in Port Klang, Malaysia.
      Three stations had THg concentrations exceeding the threshold effect level of the
      Florida Department of Environmental Protection and the Canadian interim sediment
      quality guidelines. THg and MeHg concentrations were found to be concentrated in
      the Lumut Strait where inputs from the two most urbanized rivers in the state
      converged (i.e. Klang River and Langat River). This suggests that Hg in the study
      area likely originated from the catchments of these rivers. MeHg made up 0.06
      94.96% of the sediment's THg. There is significant positive correlation (p <
      0.01) between THg and MeHg concentrations. Significant positive correlation (p <
      0.05) was also observed between fine sediment particles (i.e. clay and silt) with
      MeHg concentrations. Sediment particle size, however, was not found to have any
      influence on THg concentrations in the sediment in the study area.

PMID- 27710881
TI  - Delayed addition of nitrogen-rich substrates during composting of municipal
      waste: Effects on nitrogen loss, greenhouse gas emissions and compost stability.
AB  - Municipal waste is usually composted with an N-rich substrate, such as manure, to
      increase the N content of the product. This means that a significant amount of
      nitrogen can be lost during composting. The objectives of this study were (i) to
      investigate the effect of split addition of a nitrogen-rich substrate (poultry
      manure) on nitrogen losses and greenhouse gas emissions during composting and to
      link this effect to different bulking agents (coffee husks and sawdust), and (ii)
      to assess the effect of split addition of a nitrogen-rich substrate on compost
      stability and sanitisation. The results showed that split addition of the
      nitrogen-rich substrate reduced nitrogen losses by 9% when sawdust was used and
      20% when coffee husks were used as the bulking agent. Depending on the bulking
      agent used, split addition increased cumulative N2O emissions by 400-600%
      compared to single addition. In contrast, single addition increased methane
      emissions by up to 50% compared to split addition of the substrate. Hence, the
      timing of the addition of the N-rich substrate had only a marginal effect on
      total non-CO2 greenhouse gas emissions. Split addition of the N-rich substrate
      resulted in compost that was just as stable and effective at completely
      eradicating weed seeds as single addition. These findings therefore show that
      split addition of a nitrogen-rich substrate could be an option for increasing the
      fertilising value of municipal waste compost without having a significant effect
      on total greenhouse gas emissions or compost stability.

PMID- 27710882
TI  - Variability of disinfection by-products at a full-scale treatment plant following
      rainfall events.
AB  - The quality of drinking water sources can decrease when contaminants are
      transported by overland and subsurface flow and discharged into surface waters
      following rainfall events. Increases in organic contaminants such as road salts
      and organic matter may occur and potentially modify disinfection by-products
      (DBPs) concentration and speciation. This study investigated the effects of
      various spring rainfall events on the quality of treated waters at a large water
      treatment plant through the implementation of intensive water quality monitoring
      of raw, filtered and treated waters during different rainfall events. DBPs (four
      trihalomethanes and six haloacetic acids) and their explanatory variables (pH,
      turbidity, water temperature, specific ultraviolet absorbance, total and
      dissolved organic carbon, bromide and chlorine dose) were measured during four
      rainfall events. The results showed that water quality degrades during and
      following rainfall, leading to small increases in trihalomethanes (THM4) and
      haloacetic acids (HAA6) in treated waters. While THM4 and HAA6 levels remained
      low during the pre-rainfall period (<9 MUg/L) for the four sampling campaigns,
      small increases in THM4 and HAA6 during and after spring rainfall events were
      observed. During the rainfall and post-rainfall periods, concentration peaks
      corresponding to 3-fold and 2-fold increases (respectively 27.5 MUg/L for THM4
      and 12.6 MUg/L for HAA6) compared to pre-rainfall levels were also measured. A
      slight decrease in harmful brominated THM and HAA proportion was also observed
      following rainfall events.

PMID- 27710883
TI  - Liquid chromatography/high resolution tandem mass spectrometry - Tool for the
      study of polyphenol profile changes during micro-scale biogas digestion of grape
      marcs.
AB  - A microscale discontinuous fermenter was used for anaerobic digestion of wine
      waste - a hardly gasifiable feedstock material. Efficiency of biogas production,
      i.e. changes in content of nitrogen, oxygen, carbon dioxide and methane in gas
      phase, was monitored by gas chromatography/mass spectrometry. Liquid
      chromatography/high resolution tandem mass spectrometry in combination with
      principal component analysis and orthogonal projection to latent structures was
      used to reveal main chemical differences of gasified wine waste mixture from
      commonly used ones in agricultural biogas plants. Compounds with particular
      polyphenolic structures appeared among the most distinctive markers. Analysis of
      samples collected during acidogenic phase and unstabilized methanogenesis
      indicates formation of certain dihydro-flavonoids in early stages of the process
      and their consequent degradation. Due to formerly described higher toxicity of
      some dihydroflavonoids (e.g. taxifolin) compared to their more common
      counterparts (e.g. quercetin, malvidin etc.), unstabilized digestate would
      represent a potential environmental risk when used as a fertilizer deserving a
      proper control.

PMID- 27710884
TI  - Selective dissolution followed by EDDS washing of an e-waste contaminated soil:
      Extraction efficiency, fate of residual metals, and impact on soil environment.
AB  - To enhance extraction of strongly bound metals from oxide minerals and organic
      matter, this study examined the sequential use of reductants, oxidants, alkaline
      solvents and organic acids followed by a biodegradable chelating agent (EDDS,
      [S,S]-ethylene-diamine-disuccinic-acid) in a two-stage soil washing. The soil was
      contaminated by Cu, Zn, and Pb at an e-waste recycling site in Qingyuan city,
      China. In addition to extraction efficiency, this study also examined the fate of
      residual metals (e.g., leachability, bioaccessibility, and distribution) and the
      soil quality parameters (i.e., cytotoxicity, enzyme activities, and available
      nutrients). The reductants (dithionite-citrate-bicarbonate and hydroxylamine
      hydrochloride) effectively extracted metals by mineral dissolution, but elevated
      the leachability and bioaccessibility of metals due to the transformation from
      Fe/Mn oxides to labile fractions. Subsequent EDDS washing was found necessary to
      mitigate the residual risks. In comparison, prior washing by oxidants
      (persulphate, hypochlorite, and hydrogen peroxide) was marginally useful because
      of limited amount of soil organic matter. Prior washing by alkaline solvents
      (sodium hydroxide and sodium bicarbonate) was also ineffective due to metal
      precipitation. In contrast, prior washing by low-molecular-weight organic acids
      (citrate and oxalate) improved the extraction efficiency. Compared to
      hydroxylamine hydrochloride, citrate and oxalate induced lower cytotoxicity
      (Microtox) and allowed higher enzyme activities (dehydrogenase, acid phosphatase,
      and urease) and soil nutrients (available nitrogen and phosphorus), which would
      facilitate reuse of the treated soil. Therefore, while sequential washing proved
      to enhance extraction efficacy, the selection of chemical agents besides EDDS
      should also include the consideration of effects on metal
      leachability/bioaccessibility and soil quality.

PMID- 27710885
TI  - Removal of natural organic matter (NOM) and its constituents from water by
      adsorption - A review.
AB  - Natural organic matter (NOM) is produced through metabolic reactions in water
      supply in drinking water sources and has been reported to cause several problems
      including objectionable taste and color of water, formation of disinfection by
      products (DBPs) and reducing the amount of dissolved oxygen in water. The removal
      of NOM and its constituents from water is a challenging issue worldwide. Many
      technologies have been examined for this purpose. The properties and amount of
      NOM, however, can significantly affect the process efficiency. In the present
      work, an overview of the recent research studies dealing with adsorption method
      for the removal of NOM and related compounds from water is presented. A wide
      variety of conventional and non-conventional adsorbents have been reviewed for
      their potential in NOM removal from water. As revealed from the literature
      reviewed, modified adsorbents, composite materials and few nanomaterials have
      shown promising results for NOM removal from water. The main findings obtained
      for the removal of NOM using different adsorbents have been discussed in this
      review.

PMID- 27710886
TI  - Developmental effects of fipronil on Japanese Medaka (Oryzias latipes) embryos.
AB  - Pesticides in urban runoff are a major source of pollutants in aquatic
      ecosystems. Fipronil, a phenylpyrazole insecticide, found in structural pest
      control products, turf grass control, and home pet flea medication, has recently
      increased in use and is commonly detected in urban runoff. However, little is
      known about the effects of fipronil on aquatic organisms at early developmental
      stages. Here, we evaluated toxicity of fipronil to embryos of Japanese Medaka
      (Oryzias latipes, Qurt strain) using a high-throughput 96-well plate toxicity
      test. Male and female embryos (<6 h post fertilization) were exposed to
      concentrations of fipronil ranging from 0.1 to 910 MUg L-1 for 14 days or until
      hatching. Embryos were subjected to gross and microscopic examinations of
      developmental adverse effects as well as transcriptome analysis using RNA-seq.
      Results indicated a positive dose-response in reduced hatching success, increased
      gross deformity (tail curvature) at a lowest-observed-effect concentration (LOEC)
      of 200 MUg L-1 and delayed hatching (~1 day at the highest concentration, LOEC =
      600 MUg L-1). The transcriptome analysis indicated that fipronil exposure
      enhanced expression of titin and telethonin, which are responsible for muscle
      development. It is therefore possible that the formation of a tail curvature is
      due to asymmetrical overgrowth of muscle. Our results indicate that sub-lethal
      effects occur in embryonic stages of an aquatic vertebrate following exposure to
      high concentrations of fipronil, although no adverse effects at the highest
      published environmentally relevant concentration (6.3 MUg L-1) were observed.

PMID- 27710887
TI  - Separation of chlorinated diastereomers of decarboxy-betacyanins in
      myeloperoxidase catalyzed chlorinated Beta vulgaris L. extract.
AB  - A comparative chromatographic evaluation of chlorinated decarboxylated betanins
      and betanidins generated under activity of hypochlorous acid exerted upon these
      highly antioxidative potent decarboxylated pigments derived from natural sources
      was performed by LC-DAD-ESI-MS/MS. Comparison of the chromatographic profiles of
      the chlorinated pigments revealed two different directions of retention changes
      in relation to the corresponding substrates. Chlorination of all betacyanins that
      are decarboxylated at carbon C-17 results in an increase of their retention
      times. In contrast, all other pigments (the non-decarboxylated betacyanins as
      well as 2-decarboxy- and 15-decarboxy-derivatives) exhibit lower retention after
      chlorination. During further chromatographic experiments based upon chemical
      transformation of the related pigments (decarboxylation and deglucosylation), the
      compounds' structures were confirmed. The elaborated method for determination of
      chlorinated pigments enabled analysis of a chlorinated red beet root extract that
      was submitted to the MPO/H2O2/Cl- system acting under inflammation-like
      conditions (pH 5). This indicates a promising possibility for measurement of
      these chlorinated pigments as indicators of specific inflammatory states wherein
      betacyanins and decarboxylated betacyanins act as hypochlorite scavengers.

PMID- 27710888
TI  - Comparative pharmacokinetic analysis of extracts of crude and wine-processed
      Dipsacus asper in rats by a sensitive ultra performance liquid chromatography
      tandem mass spectrometry approach.
AB  - The purpose of this study is to establish and validate an UPLC-MS/MS approach to
      determine 4-caffeoylquinic acid, chlorogenic acid, 3,5-dicaffeoylquinic acid,
      loganic acid, loganin, sweroside, dipsacoside B and asperosaponin VI from
      extracts of crude and wine-processed Dipsacus asper in biological samples and
      apply the approach to a comparative pharmacokinetic study. A Waters BEH C18 UPLC
      column was employed with acetonitrile/0.2% formic acid-water as mobile phases.
      The mass analysis was carried out in a triple quadrupole mass spectrometer using
      multiple reaction monitoring (MRM) with negative scan mode. A one-step protein
      precipitation by acetonitrile was performed to extract the eight analytes from
      plasma. Our results revealed that all of the calibration curves displayed good
      linear regression (r2>0.9990). The lower limits of quantification (LLOQ) were
      determined as 10.0, 9.6, 8.9, 9.1, 9.2, 9.8, 10.1 and 9.8ng/mL. The intra-day and
      inter-day precisions (RSD) of the eight compounds at high, medium and low levels
      were less than 4.94% and the bias of the accuracies ranged from -3.89% to
      3.95%.The extraction recoveries of the eight compounds were from 90.4% to 100.2%
      and the matrix effects ranged from 89.3% to 100.1%. The stabilities of these
      compounds were investigated by analyzing six replicates of QC samples at three
      different concentrations following storage at 25 degrees C for 4h, -80 degrees C
      for 30days, three-freeze-thaw cycles, and 4 degrees C for 24h. All the samples
      showed satisfactory precision and accuracy after various stability tests.
      Pharmacokinetic parameters were estimated using a non-compartment model. Compared
      with the crude group, the parameters of Cmax and AUC0-t of 4-caffeoylquinic acid,
      loganic acid, loganin and asperosaponin VI increased remarkably (p<0.05) after
      oral administration of the aqueous extract of wine-processed Dipsacus asper,
      indicating that wine-processing could enhance bioavailability of 4-caffeoylquinic
      acid, loganic acid, loganin and asperosaponin VI.

PMID- 27710889
TI  - Measurement of neosaxitoxin in human plasma using liquid-chromatography tandem
      mass spectrometry: Proof of concept for a pharmacokinetic application.
AB  - Neosaxitoxin, a member of the saxitoxin family of paralytic shellfish poisoning
      toxins, has shown potential as an effective, long-acting, anesthetic. We describe
      the development and validation of a highly sensitive method for measurement of
      neosaxitoxin in human plasma using liquid chromatography tandem mass spectrometry
      (LC-MS/MS) and provide evidence for its use in a human pharmacokinetic study.
      Samples were prepared using cation exchange solid phase extraction followed by
      hydrophilic interaction liquid chromatography and MS/MS detection in positive
      electrospray ionization mode. Multiple reaction monitoring was used to monitor
      neosaxitoxin (m/z 316.17>220.07) and the internal standard analogue
      decarbamoylneosaxitoxin (m/z 273.12>180.00). The method was validated for lower
      limit of quantification, precision, accuracy, linearity and matrix effect. The
      stability of neosaxitoxin in plasma matrix at various storage conditions was also
      investigated. Standard curves for calibration were linear (r>0.995) across the
      assay calibration range, 10 to 1000pg/mL. The analytical measurable range of the
      assay was 10-10,000pg/mL in plasma matrix. This method has demonstrated excellent
      sensitivity demonstrating a lower limit of quantification in human plasma of
      10pg/mL. The mean, inter-batch variation was <5.2% across the concentration range
      30 to 800pg/mL. This method was successfully used in a phase 1 trial to
      investigate the pharmacokinetic profile of neosaxitoxin in humans following the
      intravenous administration of the drug at a range of doses up to 40MUg. We
      conclude that our high-sensitivity method for measurement of neosaxitoxin in
      human plasma is capable of supporting future clinical trials.

PMID- 27710890
TI  - Development and validation of reverse phase high performance liquid
      chromatography for citral analysis from essential oils.
AB  - Citral is a widely used monoterpene aldehyde in aromatherapy, food and pesticide
      industries. A new validated reverse phase high performance liquid chromatography
      (RP - HPLC) procedure for the detection and quantification of cis-trans isomers
      of citral was developed. The RP-HPLC analysis was carried out using Enable C -
      18G column (250*4.6mm, 5MU), with acetonitrile and water (70: 30) mobile phase in
      isocratic mode at 1mL/min flow. A photodiode array (PDA) detector was set at
      233nm for the detection of citral. The method showed linearity, selectivity and
      accuracy for citral in the range of 3-100MUg/mL. In order to compare the new RP
      HPLC method with the available methods, one of the commercially available
      essential oil from Cymbopogon flexuosus was analyzed using new RP-HPLC method and
      the same was analyzed using GC-MS for the comparison of the method for the
      detection of citral. The GC-MS analysis was done using mass selective detector
      (MSD) showed citral content to be of 72.76%; wherein the new method showed to
      contain that same at 74.98%. To prove the application of the new method,
      essential oils were extracted from lemongrass, lemon leaves and mosambi peels by
      steam distillation. The citral content present in the essential and also in the
      condensate was analyzed. The method was found to be suitable for the analysis of
      citral in essential oils and water based citral formulations with a very good
      resolution of its components geranial and neral.

PMID- 27710891
TI  - The study of doping market: How to produce intelligence from Internet forums.
AB  - Despite the predominant role played by Internet in the distribution of doping
      substances, little is currently known about the online offer of doping products.
      Therefore, the study focuses on the detection of doping substances and suppliers
      discussed in Internet forums. It aims at having a comprehensive understanding of
      products and sellers to lead an operational monitoring of the online doping
      market. Thirteen community forums on the Internet were investigated and one
      million topics were extracted with source code scrappers. Then, a semantic
      analysis was conducted with a semi-automatic process to classify the relevant
      words according to doping matters. Additionally, the ranking of doping products,
      active substances and suppliers in regards to the number of contributors to the
      forums were established and analyzed over time. Finally, promotion methods of
      suppliers were evaluated. The results show that anabolic androgenic steroids,
      used to enhance body image and performance, are the most discussed type of
      products. A temporal analysis illustrates the stability of the most popular
      products as well as the emergence of new products such as peptides (e.g. CJC
      1295). 327 suppliers were detected, mostly with dedicated websites or direct
      sales by e-mail as selling methods. Globally, the implemented methodology shows
      its ability to detect products and suppliers as well as to follow their temporal
      trends. The intelligence will serve the definition of online monitoring
      strategies (e.g. the selection of appropriate keywords). Additionally, it also
      allows the adjustment of customs inspection strategies and anti-doping analysis
      by monitoring the popular and emerging substances.

PMID- 27710892
TI  - Solar-driven thermo- and electrochemical degradation of nitrobenzene in
      wastewater: Adaptation and adoption of solar STEP concept.
AB  - The STEP concept has successfully been demonstrated for driving chemical reaction
      by utilization of solar heat and electricity to minimize the fossil energy,
      meanwhile, maximize the rate of thermo- and electrochemical reactions in
      thermodynamics and kinetics. This pioneering investigation experimentally exhibit
      that the STEP concept is adapted and adopted efficiently for degradation of
      nitrobenzene. By employing the theoretical calculation and thermo-dependent
      cyclic voltammetry, the degradation potential of nitrobenzene was found to be
      decreased obviously, at the same time, with greatly lifting the current, while
      the temperature was increased. Compared with the conventional electrochemical
      methods, high efficiency and fast degradation rate were markedly displayed due to
      the co-action of thermo- and electrochemical effects and the switch of the
      indirect electrochemical oxidation to the direct one for oxidation of
      nitrobenzene. A clear conclusion on the mechanism of nitrobenzene degradation by
      the STEP can be schematically proposed and discussed by the combination of thermo
      and electrochemistry based the analysis of the HPLC, UV-vis and degradation
      data. This theory and experiment provide a pilot for the treatment of
      nitrobenzene wastewater with high efficiency, clean operation and low carbon
      footprint, without any other input of energy and chemicals from solar energy.

PMID- 27710893
TI  - Pitch perception deficits in nonverbal learning disability.
AB  - The nonverbal learning disability (NLD) is a neurological dysfunction that
      affects cognitive functions predominantly related to the right hemisphere such as
      spatial and abstract reasoning. Previous evidence in healthy adults suggests that
      acoustic pitch (i.e., the relative difference in frequency between sounds) is,
      under certain conditions, encoded in specific areas of the right hemisphere that
      also encode the spatial elevation of external objects (e.g., high vs. low
      position). Taking this evidence into account, we explored the perception of pitch
      in preadolescents and adolescents with NLD and in a group of healthy participants
      matched by age, gender, musical knowledge and handedness. Participants performed
      four speeded tests: a stimulus detection test and three perceptual categorization
      tests based on colour, spatial position and pitch. Results revealed that both
      groups were equally fast at detecting visual targets and categorizing visual
      stimuli according to their colour. In contrast, the NLD group showed slower
      responses than the control group when categorizing space (direction of a visual
      object) and pitch (direction of a change in sound frequency). This pattern of
      results suggests the presence of a subtle deficit at judging pitch in NLD along
      with the traditionally-described difficulties in spatial processing.

PMID- 27710894
TI  - Ginger extract protects rat's kidneys against oxidative damage after chronic
      ethanol administration.
AB  - Chronic alcohol ingestion is associated with pronounced detrimental effects on
      the renal system. In the current study, the protective effect of ginger extract
      on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C,
      glomerular filtration rate, and pathological changes such as cell proliferation
      and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three
      groups and were treated as follows: (1) control, (2) ethanol and (3) ginger
      extract treated ethanolic (GETE) groups. After a six weeks period of treatment,
      the results revealed proliferation of glomerular and tubular cells, fibrosis in
      glomerular and peritubular and a significant rise in the level of 8-OHdG,
      cystatin C, plasma urea and creatinine. Moreover, compared to the control group,
      the ethanol group showed a significant decrease in the urine creatinine and
      creatinine clearance. In addition, significant amelioration of changes in the
      structure of kidneys, along with restoration of the biochemical alterations were
      found in the ginger extract treated ethanolic group, compared to the ethanol
      group. These findings indicate that ethanol induces kidneys abnormality by
      oxidative DNA damage and oxidative stress, and that these effects can be
      alleviated using ginger as an antioxidant and anti-inflammatory agent.

PMID- 27710895
TI  - CD200Fc attenuates inflammatory responses and maintains barrier function by
      suppressing NF-kappaB pathway in cigarette smoke extract induced endothelial
      cells.
AB  - BACKGROUND: Recent evidence suggests that CD200 fusion protein (CD200Fc), a
      CD200R1 agonist may attenuate inflammatory responses in autoimmune diseases and
      neuro-degeneration. While, little is known about the function of CD200Fc in
      cigarette smoke extract (CSE)-induced mouse Cardiac Microvascular Endothelial
      Cells (mCMECs). The present study was designed to elucidate the effects of
      CD200Fc on CSE-induced vascular endothelial barrier (VEB) dysfunction and
      inflammatory responses, which is a highly clinically relevant model of smoking
      related cardiovascular diseases. METHODS: mCMECs were pre-treated with 1, 10 and
      100MUg/ml CD200Fc for 24h respectively, and then treated with 250MUg/ml CSE for
      different times (24h or 120min). The transepithelial electrical resistance (TEER)
      and transport of fluorescent markers were used to measure VEB function in CSE
      induced mCMECs. Western blot and immunofluorescent staining analysis were used to
      detect the expression of tight junction proteins, such as Zona Occludens-1 (ZO-1)
      and Claudin-1 in CSE-induced mCMECs. We measured the expression of pro
      inflammatory cytokines in CSE-induced mCMECs by using ELISA and RT-PCR. In
      addition, the NF-kappaB activity in CSE-induced mCMECs were investigated by using
      nuclear/cytosol fractionation and western blot analysis. RESULTS: In vitro
      treatment with CSE increased the transport of fluorescent markers and decreased
      TEER levels in mCMECs, respectively, which were attenuated by CD200Fc (10 and
      100MUg/ml) pretreatment. The CSE-induced up-regulation of pro-inflammatory
      cytokines such as Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase
      (iNOS), platelet endothelial cell adhesion molecule-1 (PECAM-1), vascular cell
      adhesion molecule-1 (ICAM-1), Prostaglandin E2 (PGE2), tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6) and IL-8 in mCMECs was also abrogated by
      CD200Fc (10 and 100MUg/ml) pretreatment. CD200Fc also inhibited CSE-induced
      nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)
      activation in mCMECs, such as inhibition of its DNA binding activity,
      phosphorylated expression, and translocation to nucleus. CONCLUSION: Thus,
      CD200Fc exert anti-inflammatory effect and protect VEB function in CSE-induced
      mCMECs. The vasoprotective effects of CD200Fc may be specifically beneficial in
      pathophysiological conditions associated with smoking related cardiovascular
      diseases.

PMID- 27710896
TI  - miRNA-133b and miRNA-135a induce apoptosis via the JAK2/STAT3 signaling pathway
      in human renal carcinoma cells.
AB  - Aberrantly expressed microRNAs (miRNAs) are involved in many diseases including
      cancer. In clear cell renal cell carcinoma (ccRCCs) expression of miR-133b and
      miR-135a is reduced compared to control tissue and other sarcomas but the
      functional effects of this downregulation are not fully understood. This study
      aimed at evaluating the miR-133b and miR-135a expression profiles in different
      RCC subtypes and the functional role of these miRNAs. Viability and apoptosis
      were examined in three different ccRCC cell lines (786-O, A498 and SN12-PM6)
      after over-expression of these miRNAs. The modulation of JAK2 and the JAK2/STAT3
      pathways was determined by Western blot. Transient transfection of miR-133b and
      miR-135a reduced viability and induced apoptosis by inhibition of JAK2 expression
      and its phosphorylation and activation of caspase 3 and 7 in all three ccRCC cell
      lines. p-STAT3 and Bcl-2 expression was reduced after miRNA transfection whereas
      only slight influence on Bcl-2 L11 (BIM) was detected. Our results demonstrate
      that miR-133b and miR-135a which are down-regulated in wildtype and mutated
      ccRCCs, induce apoptosis in vitro by a signaling cascade involving JAK2, STAT3
      and Bcl-2. Therefore, over-expression of these miRNAs seems to functionally
      counteract oncogenic signalling pathways in ccRCCs.

PMID- 27710897
TI  - BZ-26, a novel GW9662 derivate, attenuated inflammation by inhibiting the
      differentiation and activation of inflammatory macrophages.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is considered to be
      an important transcriptional factor in regulation of macrophages differentiation
      and activation. We have synthesized a series of novel structural molecules based
      on GW9662's structure (named BZ-24, BZ-25 and BZ-26), and interaction activity
      was calculated by computational docking. BZ-26 had shown stronger interaction
      with PPARgamma and had higher transcriptional inhibitory activity of PPARgamma
      with lower dosage compared with GW9662. BZ-26 was proved to inhibit inflammatory
      macrophage differentiation. LPS-induced acute inflammation mouse model was
      applied to demonstrate its anti-inflammatory activity. And the results showed
      that BZ-26 administration attenuated plasma tumor necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) secretion, which are vital cytokines in acute
      inflammation. The anti-inflammatory activity was examined in THP-1 cell line, and
      TNF-alpha, IL-6 and MCP-1, were significantly inhibited. The results of Western
      blot and luciferase reporter assay indicated that BZ-26 not only inhibited NF
      kappaB transcriptional activity, but also abolished LPS-induce nuclear
      translocation of P65. We also test BZ-26 action in tumor-bearing chronic
      inflammation mouse model, and BZ-26 was able to alter macrophages phenotype,
      resulting in antitumor effect. All our data revealed that BZ-26 modulated LPS
      induced acute inflammation via inhibiting inflammatory macrophages
      differentiation and activation, potentially via inhibition of NF-kappaB signal
      pathway.

PMID- 27710899
TI  - Proliferation-enhancing effects of gastrodin on RSC96 Schwann cells by regulating
      ERK1/2 and PI3K signaling pathways.
AB  - The proliferation and migration of Schwann cells (SCs) are essential in the
      process of peripheral nerve repair. A large amount of studies focused on the
      promotion of the growth of SCs for cell based therapy. Gastrodin (GAS), the main
      constituent of a Chinese traditional herbal medicine named Gastrodia elata Blume,
      has been reported to be associated with neuroprotective properties. Besides, GAS
      activated MAPK and PI3K signaling pathways which are often involved in growth of
      nerve cells were also reported. Based on the hypothesis that GAS may have an
      effect on SCs growth, we studied the effect of GAS on rat RSC96 Schwann cells
      (SCs) and further explored the underlying mechanism. Various concentration of GAS
      (0MUM, 50MUM, 100MUM, and 200MUM) was used for treatment of RSC96 SCs, with the
      cell proliferation and gene expression of several neurotrophic factors to be
      detected. Regulation of MAPK and PI3K signaling pathways were assayed by
      detecting phosphorylation of ERK1/2 and Akt. The results showed that GAS could
      effectively promote proliferation of RSC96 SCs in a dose- and time-dependent
      manner. The best performance was obtained at the concentration of 200MUM.
      Exploration of the underlying mechanism showed that GAS probably affects SCs
      metabolism through inhibiting ERK1/2 phosphorylation and activating Akt
      phosphorylation in RSC96 SCs. This study may provide reference for its
      application in treatment of peripheral nerve injuries.

PMID- 27710898
TI  - Nephro-protective action of P. santalinus against alcohol-induced biochemical
      alterations and oxidative damage in rats.
AB  - The present study investigated the antioxidant potential of P. santalinus
      heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The
      results indicated an increase in the concentration of kidney damage plasma
      markers, urea and creatinine with a concomitant decrease in the concentration of
      uric acid in alcohol-administered rats. A significant decrease in plasma
      electrolytes and mineral levels with increased kidney thiobarbituric acid
      reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE
      treatment to alcohol-administered rats effectively prevented the elevation in
      TBARS and NOx levels. Decreased activity of Na+/K+-ATPase in alcohol administered
      rats was brought to near normal levels with treatment of PSE. Chronic alcohol
      consumption affects antioxidant enzymatic activity and reabsorption function of
      the kidney which is evident from the decreased level of GSH as well as the
      activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
      (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However,
      treatment with PSE to alcohol-administered rats significantly enhanced these
      enzymatic activities and reduced glutathione (GSH) content close to normal level.
      Alcohol-induced organ damage was evident from morphological changes in the
      kidney. Nevertheless, administration of PSE effectively restored these
      morphological changes to normal. The flavonoid and tannoid compounds might have
      protective activity against alcohol-induced oxidative/nitrosative stress mediated
      kidney damage.

PMID- 27710900
TI  - Wild-type hen egg white lysozyme aggregation in vitro can form self-seeding
      amyloid conformational variants.
AB  - Misfolded beta-sheet-rich protein aggregates termed amyloid, deposit in vivo
      leading to debilitating diseases such as Alzheimer's, prion and renal amyloidosis
      diseases etc. Strikingly, amyloid can induce conversion of their natively folded
      monomers into similarly aggregated conformation via 'seeding'. The specificity of
      seeding is well documented in vivo for prions, where prion-variants arising from
      conformationally altered amyloids of the same protein, faithfully seed monomers
      into amyloid displaying the original variant's conformation. Thus far, amyloid
      variant formation is reported only for a few non-prion proteins like Alzheimer's
      Abeta42-peptide and beta-2 microglobulin, however, their conformational cross
      seeding capabilities are unexplored. While mutant human lysozyme causes renal
      amyloidosis, the hen egg white lysozyme (HEWL) has been extensively investigated
      in vitro as a model amyloid protein. Here we investigated if wild-type HEWL could
      form self-seeding amyloid variants to examine if variant formation is more wide
      spread. We found that HEWL aggregates formed under quiescent versus agitated
      conditions, displayed different particle sizes, detergent stabilities & beta
      sheet content, and they only seeded monomeric HEWL under similar incubation
      conditions, but not under swapped incubation conditions thereby showing amyloid
      variant formation by HEWL analogous to prion variants. This may have implications
      to the amyloidosis caused by different mutants of human lysozyme.

PMID- 27710901
TI  - Length and sequence effect on the B-Z transition of [d(A-T)n]2 oligonucleotide
      induced by a cationic porphyrin.
AB  - trans-BMPyP induced the B-Z transition for alternated AT oligonucleotides as it
      was evident by inversed CD spectrum. The transition occurred simultaneously with
      appearance of the extensive stacking of porphyrin. Complete B-Z transition
      required at least 14 base-pairs long. Insertion of one or two GC base pairs
      prevented the B-Z transition.

PMID- 27710902
TI  - Childhood trauma and HPA axis functionality in offspring of bipolar parents.
AB  - Children of a parent with bipolar disorder (bipolar offspring) have an increased
      risk for mood disorders. While genetic factors play a significant role in this
      population, susceptibility to environmental stress may also significantly
      contribute to this vulnerability for mood disorders. Childhood trauma has
      consistently been found to increase the risk for mood disorders, with persisting
      consequences for hypothalamic-pituitary-adrenal (HPA) axis functionality.
      However, it is currently unknown whether childhood trauma specifically affects
      HPA axis activity in individuals with a familial risk for bipolar disorder.
      Therefore, we investigated the effects of childhood trauma on daytime and evening
      cortisol levels and dexamethasone suppression in bipolar offspring (N=70) and
      healthy controls (N=44). In our study we found no significant differences in
      daytime and evening cortisol levels as well as dexamethasone suppression between
      bipolar offspring and healthy controls (all p-values>0.43). In contrast,
      childhood trauma differentially affected daytime cortisol levels in the bipolar
      offspring compared to healthy controls (childhood trauma X bipolar offspring
      interaction, beta=-7.310, p=0.0414) with an effect of childhood trauma on daytime
      cortisol in bipolar offspring at trend level (p=0.058). In the bipolar offspring
      group, lifetime or current psychiatric diagnoses, and stressful life events
      separately did not affect cortisol levels or dexamethasone suppression (all p
      values>p=0.50). These findings were independent of current or lifetime
      psychiatric diagnosis. In conclusion, trauma-related changes in daytime HPA axis
      activity appear to be a specific trait in bipolar offspring who have increased
      risk for mood disorders compared to healthy individuals.

PMID- 27710903
TI  - How China achieved its 11th Five-Year Plan emissions reduction target: A
      structural decomposition analysis of industrial SO2 and chemical oxygen demand.
AB  - To curb the increasing pollutant emissions that have accompanied rapid economic
      growth, China implemented a mandatory emissions control system since the 11th
      Five-Year Plan (FYP) period, and the emission reduction targets have been met and
      even exceeded. This article explores how China achieved its emissions reduction
      targets by systematically identifying the main emission reduction pathways,
      including both the environmental and economic factors, and evaluates the
      contribution of each factor using structure decomposition analysis. A study of
      the two key controlled pollutants, industrial sulfur dioxide (SO2) and chemical
      oxygen demand (COD), during the 11th FYP period showed that (i) changes in the
      end-of-pipe treatment and pollutant generation coefficient were the dominant
      contributors to emissions reduction. The power and metal smelting sectors played
      important roles in SO2 abatement, while the paper products and food products
      sectors were important in COD reduction; (ii) changes to the input coefficient
      increased overall emissions although there was a decrease in SO2 emissions in
      2007-2010 mainly due to input structure improvements in the construction sector;
      (iii) the trade effect largely offset the domestic emission reduction effects,
      although the trade effect declined during the study period; (iv) domestic demand
      was the main factor increasing domestic emissions; domestic investment changes
      (especially in the construction sector) were the major contributor to increases
      in SO2 emissions, and final consumption changes (especially consumption in the
      food production sector) were the main contributor to the increase in COD
      emissions. The results yield important implications for China's pollution
      emissions control policies.

PMID- 27710904
TI  - Polychlorinated biphenyl exposure and deiodinase activity in young infants.
AB  - BACKGROUND: Several studies have shown effects of polychlorinated biphenyls
      (PCBs) on serum thyroid hormone levels in pregnant woman and their infants, while
      other studies did not find such effects. How PCBs might affect thyroid hormone
      metabolism, is still unclear. Potential mechanisms are direct influence on the
      thyroid gland, binding to thyroid binding proteins, increased excretion or
      metabolism of thyroid hormones by deiodinases or sulfatases. It is also not well
      known whether the effect on thyroid hormone levels is caused by PCBs themselves,
      or by their hydroxylated metabolites (OH-PCBs). OBJECTIVE: To determine the
      effects of perinatal exposure to PCBs and OH-PCBs on thyroid hormone levels in
      cord blood and in serum of newborn infants. METHODS: In a Dutch cohort of 100
      mother-infant pairs, exposed to background PCB levels, correlations were assessed
      between 10 PCBs and 6 OH-PCBs in maternal blood during pregnancy and serum
      thyroxine (T4), T4 sulfate (T4S), triiodothyronine (T3), reverse T3 (rT3),
      thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) levels in
      cord blood and in serum of three- and 18-month-old infants. We corrected for age
      of the mother, gestational age, gender and type of feeding. RESULTS: After
      correction, prenatal levels of three of 10 measured PCBs showed a positive
      correlation with cord serum T3, and four PCBs showed a negative correlation with
      cord serum rT3. After correction, two PCBs and the sum of the 10 measured PCBs
      were positively correlated with the cord serum T3/rT3 ratio, an indicator of
      deiodinase 3 activity. No correlations were found between PCBs and T4, TSH and
      TBG in cord blood. 4-OH-PCB-107 was correlated with T4 at 3months and T4, T4S and
      T3 at 18months. CONCLUSION: Our results suggest that PCBs have a negative effect
      on deiodinase type 3 activity, as reflected by a positive correlation with the
      T3/rT3 ratio. We identified a potential mechanism by which PCBs may affect
      thyroid hormone metabolism during human development.

PMID- 27710905
TI  - Towards understanding the integrative approach of the water, energy and food
      nexus.
AB  - The water, energy and food nexus (WEF nexus) is currently quite popular in
      environmental management. The concept found a fertile ground in science and
      policymaking, but there is no consistent view on the meaning of integration
      within the nexus. Here, a wealth of publications is reviewed in an endeavour to:
      (1) reveal the lines of justification for the need of the WEF nexus debate and
      (2) identify the range of tools for analysing the interdependent resource issues
      of the nexus using an integrated framework of science and policy. There are three
      drivers behind the emergence of the nexus thinking. These are a) increasing
      resource interlinks due to growing scarcities, b) recent resource supply crises,
      and c) failures of sector-driven management strategies. Evaluation of the WEF
      nexus integrative debate can be carried out using four key criteria, namely
      ability to change current policy debates, issue and thinking novelty,
      practicability and measurability, and clearness and implementation roadmap. It is
      clear that, although the nexus has been quite successful in changing policy
      debates, issue prioritization is missing and seems to be left to specific case
      studies and policymakers' choices. There is a high need for 'incorporation' and
      'cross-linking' of issues between the three resources. In this regard, nexus
      governance is the missing link in the nexus debate.

PMID- 27710907
TI  - Modeling the dynamic volatile fatty acids profiles with pH and hydraulic
      retention time in an anaerobic baffled reactor during the startup period.
AB  - To predict the dynamic profiles in volatile fatty acids (VFAs) with pH and
      hydraulic retention time (HRT) during the startup of a 4-compartment ABR, a
      mathematical model was constructed by introducing pH and thermodynamic inhibition
      functions into the biochemical processes derived from the ADM1. The calibration
      of inhibition parameter for propionate uptake effectively improved the prediction
      accuracy of VFAs. The developed model could simulate the VFAs profiles very well
      no matter the observable change of pH or/and HRT. The simulation results
      indicated that both H2-producing acetogenesis and methanogenesis in the ABR would
      be inhibited with a pH less than 4.61, and the propionate oxidation could be
      thermodynamically restricted even with a neutral pH. A decreased HRT would
      enhanced the acidogenesis and H2-producing acetogenesis in the first 3
      compartments, but no observable increase in effluent VFAs could be found due to
      the synchronously enhanced methanogenesis in the last compartment.

PMID- 27710906
TI  - Explosive genetic evidence for explosive human population growth.
AB  - The advent of next-generation sequencing technology has allowed the collection of
      vast amounts of genetic variation data. A recurring discovery from studying
      larger and larger samples of individuals had been the extreme, previously
      unexpected, excess of very rare genetic variants, which has been shown to be
      mostly due to the recent explosive growth of human populations. Here, we review
      recent literature that inferred recent changes in population size in different
      human populations and with different methodologies, with many pointing to recent
      explosive growth, especially in European populations for which more data has been
      available. We also review the state-of-the-art methods and software for the
      inference of historical population size changes that lead to these discoveries.
      Finally, we discuss the implications of recent population growth on personalized
      genomics, on purifying selection in the non-equilibrium state it entails and, as
      a consequence, on the genetic architecture underlying complex disease and the
      performance of mapping methods in discovering rare variants that contribute to
      complex disease risk.

PMID- 27710908
TI  - Stimulation of waste decomposition in an old landfill by air injection.
AB  - Three pilot-scale lysimeters were operated for 4.5years to quantify the change in
      the carbon and nitrogen pool in an old landfill under various air injection
      conditions. The results indicate that air injection at the bottom layer
      facilitated homogeneous distribution of oxygen in the waste matrix. Substantial
      total organic carbon (TOC) decomposition and methane generation reduction were
      achieved. Considerable amount of nitrogen was removed, suggesting that in situ
      nitrogen removal via the effective simultaneous nitrification and denitrification
      mechanism is viable. Moreover, material mass change measurements revealed a
      slight mass reduction of aged MSW (by approximately 4.0%) after 4.5years of
      aeration. Additionally, experiments revealed that intensive aeration during the
      final stage of the experiment did not further stimulate the degradation of the
      aged MSW. Therefore, elimination of the labile fraction of aged MSW should be
      considered the objective of in situ aeration.

PMID- 27710909
TI  - Microbial conversion of mixed volatile fatty acids into microbial lipids by
      sequencing batch culture strategy.
AB  - Four mixed volatile fatty acids (VFAs) were used as sole carbon source to culture
      oleaginous yeast Cryptococcus curvatus by sequencing batch culture strategy. The
      highest lipid content (42.7%) and concentration (1.77g/L) were achieved when the
      ratio of VFAs (acetic, propionic, and butyric acids) was 6:3:1. The oleaginous
      yeast favored to use VFAs for lipid biosynthesis rather than cell proliferation.
      With regard to the utilization ratio of VFAs, acetic acid reached over 99%,
      whereas propionic acid was barely 35%. The produced lipids contained nearly 45%
      of monounsaturated fatty acids, which can be the ideal raw materials for
      biodiesel production. Additionally, the produced odd-numbered fatty acid content
      reached 23.6% when the propionate acid content of VFAs was 50%. Further analysis
      showed that increasing the ratio of acetic acid was most beneficial to cell mass
      and lipid production, whereas propionic acid and butyric acid were more conducive
      to lipid and cell mass synthesis, respectively.

PMID- 27710910
TI  - Pretreatment of food waste with high voltage pulse discharge towards methane
      production enhancement.
AB  - Anaerobic batch tests were performed to investigate the methane production
      enhancement and solid transformation rates from food waste (FW) by high voltage
      pulse discharge (HVPD) pretreatment. The total cumulative methane production with
      HVPD pretreatment was 134% higher than that of the control. The final volatile
      solids transformation rates of FW with and without HVPD pretreatment were 54.3%
      and 32.3%, respectively. Comparison study on HVPD pretreatment with acid, alkali
      and ultrasonic pretreatments showed that the methane production and COD removal
      rates of FW pretreated with HVPD were more than 100% higher than the control, but
      only about 50% higher can be obtained with other pretreatments. HVPD pretreatment
      could be a promising pretreatment method in the application of energy recovery
      from FW.

PMID- 27710911
TI  - Mechanistic insight from murine models of Netherton syndrome.
AB  - Protease regulation plays a crucial role in skin homeostasis and inflammation as
      revealed by the identification of loss-of-function mutations in SPINK5 (serine
      protease inhibitor of Kazal type 5) in Netherton sydrome (NS). SPINK5 encodes
      LEKTI (lympho-epithelial Kazal type related inhibitor), a multidomain serine
      protease inhibitor expressed in all stratified epithelia. Our laboratory has
      developed a number of murine models which have been instrumental in dissecting
      the pathogenesis of NS. This minireview discusses the major findings of these
      models and emphasizes the role of protease regulation, especially kallikrein
      related peptidases in NS.

PMID- 27710912
TI  - Highlight: remodelling the KLK landscape down under.

PMID- 27710913
TI  - Solving a case of allelic dropout in the GNPTAB gene: implications in the
      molecular diagnosis of mucolipidosis type III alpha/beta.
AB  - While being well known that the diagnosis of many genetic disorders relies on a
      combination of clinical suspicion and confirmatory genetic testing, not rarely,
      however, genetic testing needs much perseverance and cunning strategies to
      identify the causative mutation(s). Here we present a case of a thorny molecular
      diagnosis of mucolipidosis type III alpha/beta, which is an autosomal recessive
      lysosomal storage disorder, caused by a defect in the GNPTAB gene that codes for
      the alpha/beta-subunits of the GlcNAc-1-phosphotransferase. We used both cDNA and
      gDNA analyses to characterize a mucolipidosis type III alpha/beta patient whose
      clinical diagnosis was already confirmed biochemically. In a first stage only one
      causal mutation was identified in heterozygosity, the already described missense
      mutation c.1196C>T(p.S399F), both at cDNA and gDNA levels. Only after conducting
      inhibition of nonsense-mediated mRNA decay (NMD) assays and after the utilization
      of another pair of primers the second mutation, the c.3503_3504delTC deletion,
      was identified. Our findings illustrate that allelic dropout due to the presence
      of polymorphisms and/or of mutations that trigger the NMD pathway can cause
      difficulties in current molecular diagnosis tests.

PMID- 27710914
TI  - Increased oxidative stress parameters in children with moderate iodine
      deficiency.
AB  - BACKGROUND: Iodine is a part of thyroid hormones and has been reported to act
      directly as an antioxidant or induce indirectly antioxidant enzymes. This study
      aimed to assess the urinary iodine concentration and its relationship between the
      antioxidant and oxidative stress capacity in healthy school-aged children.
      METHODS: In total, 196 students from five primary schools, randomly selected
      between 9 and 12 years (mean age: 10.2+/-1.2 years), were enrolled in the study.
      Urinary iodine levels were measured by spectrophotometry with the Sandell
      Kolthoff reaction. Total antioxidant status (TAS) and total oxidant status (TOS)
      were analysed from urine samples. The ratio of TOS to TAS was regarded as an
      oxidative stress index (OSI), an indicator of the degree of oxidative status.
      RESULTS: Fifty-four percentage (107) of the children had iodine deficiency (ID)
      and the majority of them (30%) had mild ID. There was no severe-ID child in the
      population (<20 MUg/L). Urine TAS levels were significantly lower in the moderate
      ID group than in the mild-ID group (6.5+/-4.1 vs. 11.3+/-4.1 mmol, p<0.001) and
      the iodine-sufficient group (11.0+/-5.3 MUmol, p<0.001). TOS levels and OSI were
      found higher in the moderate-ID group than in the mild-ID group (4.8+/-2.1 vs.
      3.7+/-2.1 MUmol, p<0.001) and the iodine-sufficient group (4.8+/-2.1 vs. 3.4+/
      2.5 mmol, p<0.001). In the moderate-ID group, low urine iodine levels exhibited
      significant negative correlations with OSI (r=-0.660) and TOS (r=-0.248) and a
      positive correlation with TAS (r=0.475). CONCLUSIONS: We found that children with
      moderate ID were exposed to more oxidative burden than children with mild ID or
      iodine sufficiency. Increased systemic oxidative stress induced by moderate ID
      could cause development of ID-related complications and diseases. Iodine
      supplementation could have a beneficial role in the prevention of oxidative
      stress.

PMID- 27710915
TI  - Lipoprotein-associated phospholipase A2 activity and low-density lipoprotein
      subfractions after a 2-year treatment with atorvastatin in adolescents with type
      1 diabetes.
AB  - BACKGROUND: The objective of the study was to assess the effect of atorvastatin
      on inflammation markers and low-density lipoprotein (LDL) subfractions. METHODS:
      In a prospective, randomized, double-blind pilot study involving 28 adolescents
      with type 1 diabetes (T1D), lipoprotein-associated phospholipase A2 (Lp-PLA2)
      activity, high-sensitivity C-reactive protein (hsCRP), and subfractions of LDL
      were measured at baseline, after 1 year and 2 years of treatment with
      atorvastatin (10 mg/day) vs. placebo. RESULTS: For the atorvastatin group, we
      found posttreatment reductions of Lp-PLA2 activity (p<0.001), LDL cholesterol
      (p=0.001), non-small dense LDL cholesterol (p<0.001), total cholesterol
      (p<0.001), and apolipoprotein B (apo B) (p<0.001), whereas small dense LDL
      cholesterol and hsCRP did not change significantly. CONCLUSIONS: In adolescents
      with T1D, long-term treatment with atorvastatin is safe and may reduce
      cardiovascular risk by significant decreases of Lp-PLA2 activity and LDL
      cholesterol.

PMID- 27710916
TI  - Pituitary volume in children with growth hormone deficiency, idiopathic short
      stature and controls.
AB  - BACKGROUND: The objective of the study was to describe the pituitary volume (PV)
      in pediatric patients with isolated growth hormone deficiency (IGHD), idiopathic
      short stature (ISS) and normal controls. METHODS: Sixty-nine patients (57 male,
      12 female), with a mean age of 11.9 (+/-2.0), were determined to have IGHD. ISS
      was identified in 29 patients (20 male, 9 female), with a mean age of 12.7 (+/
      3.7). Sixty-six controls (28 female, 38 male), mean age 9.8 (+/-4.7) were also
      included. Three-dimensional (3D) magnetic resonance images with contrast were
      obtained to accurately measure PV. RESULTS: There was a significant difference in
      the mean PV among the three groups. The IGHD patients had a mean PV 230.8 (+/
      89.6), for ISS patients it was 286.8 (+/-108.2) and for controls it was 343.7 (+/
      145.9) (p<0.001). There was a normal increase in PV with age in the ISS patients
      and controls, but a minimal increase in the IGHD patients. CONCLUSIONS: Those
      patients with isolated GHD have the greatest reduction in PV compared to controls
      and the patients with ISS fall in between. We speculate that a possible cause for
      the slowed growth in some ISS patients might be related to diminished chronic
      secretion of growth hormone over time, albeit having adequate pituitary reserves
      to respond acutely to GH stimulation. Thus, what was called neurosecretory GHD in
      the past, might, in some patients, be relative pituitary hypoplasia and resultant
      diminished growth hormone secretion. Thus, PV determinations by magnetic
      resonance imaging (MRI) could assist in the diagnostic evaluation of the slowly
      growing child.

PMID- 27710917
TI  - Primary hyperparathyroidism may masquerade as rickets-osteomalacia in vitamin D
      replete children.
AB  - Primary hyperparathyroidism, typically a disease of the middle aged and the old,
      is less commonly seen in children. In children the disease has a bimodal age
      distribution with calcium sensing receptor mutation presenting in infancy as
      hypercalcemic crises and parathyroid adenoma or hyperplasia presenting later in
      childhood with bone disease. The childhood parathyroid adenomas are often
      familial with multiglandular disease and manifest with severe bone disease unlike
      adults. We report a series of four male patients with juvenile primary
      hyperparathyroidism, three of whom presented with bone disease masquerading as
      rickets-osteomalacia. One patient had asymptomatic hypercalcemia with short
      stature. Parathyroid adenoma was detected in all the four cases and all of them
      underwent resection of parathyroid adenomas confirmed on histopathology. Post
      surgery all the cases had initial hypocalcaemia followed by normocalcemia. One
      case developed pancreatitis after surgery even after achieving normocalcemia. We
      conclude that parathyroid adenomas, although uncommon in children, are an
      important cause of skeletal disease that may initially be confused with
      hypovitaminosis D.

PMID- 27710918
TI  - Editorial.

PMID- 27710919
TI  - Prospects for Higgs physics at energies up to 100 TeV.
AB  - We summarize the prospects for Higgs boson physics at future proton-proton
      colliders with centre of mass (c.m.) energies up to 100 TeV. We first provide the
      production cross sections for the Higgs boson of the Standard Model from 13 TeV
      to 100 TeV, in the main production mechanisms and in subleading but important
      ones such as double Higgs production, triple production and associated production
      with two gauge bosons or with a single top quark. We then discuss the production
      of Higgs particles in beyond the Standard Model scenarios, starting with the one
      in the continuum of a pair of scalar, fermionic and vector dark matter particles
      in Higgs-portal models in various channels with virtual Higgs exchange. The cross
      sections for the production of the heavier CP-even and CP-odd neutral Higgs
      states and the charged Higgs states in two-Higgs doublet models, with a specific
      study of the case of the Minimal Supersymmetric Standard Model, are then given.
      The sensitivity of a 100 TeV proton machine to probe the new Higgs states is
      discussed and compared to that of the LHC with a c.m. energy of 14 TeV and at
      high luminosity.

PMID- 27710920
TI  - An interview with Arthur J Coury: an extensively experienced perspective on
      medical device development.

PMID- 27710921
TI  - Frequency-based nanoparticle sensing over large field ranges using the
      ferromagnetic resonances of a magnetic nanodisc.
AB  - Using finite element micromagnetic simulations, we study how resonant
      magnetisation dynamics in thin magnetic discs with perpendicular anisotropy are
      influenced by magnetostatic coupling to a magnetic nanoparticle. We identify
      resonant modes within the disc using direct magnetic eigenmode calculations and
      study how their frequencies and spatial profiles are changed by the
      nanoparticle's stray magnetic field. We demonstrate that particles can generate
      shifts in the resonant frequency of the disc's fundamental mode which exceed
      resonance linewidths in recently studied spin torque oscillator devices.
      Importantly, it is shown that the simulated shifts can be maintained over large
      field ranges (here up to 1 T). This is because the resonant dynamics (the basis
      of nanoparticle detection here) respond directly to the nanoparticle stray field,
      i.e. detection does not rely on nanoparticle-induced changes to the magnetic
      ground state of the disc. A consequence of this is that in the case of small disc
      particle separations, sensitivities to the particle are highly mode- and particle
      position-dependent, with frequency shifts being maximised when the intense stray
      field localised directly beneath the particle can act on a large proportion of
      the disc's spins that are undergoing high amplitude precession.

PMID- 27710922
TI  - Hyaluronic acid-based hydrogel scaffold without angiogenic growth factors
      enhances ovarian tissue function after autotransplantation in rats.
AB  - One of the problems encountered during ovarian transplantation is that the number
      of primordial follicles in the grafts is considerably reduced 2 d after
      transplantation due to post-transplantation ischemia. This study investigates if
      the use of hyaluronic acid-based hydrogel (HABH) with and without vascular
      endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) could
      prevent or minimize ischemia-induced follicle loss during ovarian
      autotransplantation and thereby restore ovarian tissue function in the rat model.
      In this study, twenty four female rats were subjected to bilateral ovariectomy
      and were randomly divided into 3 groups for ovarian tissue autotransplantation.
      Group A included rats with ovarian tissue without HABH, VEGF and bFGF, group B
      comprised rats with ovarian tissue encapsulated with HABH and group C had rats
      with ovarian tissue encapsulated with HABH containing VEGF and bFGF. Three days
      after transplantation, the grafts were assessed through histological and hormonal
      analyses. Apoptotic, angiogenic and maturation genes expressions were also
      analyzed. The mean number of follicles in all developmental stages increased in
      group B (P  <  0.05). The level of FSH decreased in group B (P  <  0.05) whereas,
      the expression level of VEGF gene increased in group B (P  <  0.05). No
      significant changes were observed in the expression levels of maturation and
      apoptotic genes in all groups. In conclusion, ovarian encapsulation with HABH
      alone can prevent or minimize ischemia-induced follicle loss, preserve the
      follicular pool, promote follicular survival, facilitate angiogenesis, and
      restore hormone levels. However, its efficiency in a clinical setting and in
      comparison with other hydrogels needs further investigation.

PMID- 27710923
TI  - In vitro characterization of electrochemically compacted collagen matrices for
      corneal applications.
AB  - Loss of vision due to corneal disease is a significant problem worldwide.
      Transplantation of donor corneas is a viable treatment option but limitations
      such as short supply and immune-related complications call for alternative
      options for the treatment of corneal disease. A tissue engineering-based approach
      using a collagen scaffold is a promising alternative to develop a bioengineered
      cornea that mimics the functionality of native cornea. In this study, an
      electrochemical compaction method was employed to synthesize highly dense and
      transparent collagen matrices. We hypothesized that chemical crosslinking of
      electrochemically compacted collagen (ECC) matrices will maintain transparency,
      improve stability, and enhance the mechanical properties of the matrices to the
      level of native cornea. Further, we hypothesized that keratocyte cell viability
      and proliferation will be maintained on crosslinked ECC matrices. The results
      indicated that uncrosslinked and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-N
      hydroxysuccinimide (EDC-NHS) crosslinked ECC matrices were highly transparent
      with light transmission measurements comparable to native cornea. Stability tests
      showed that while the uncrosslinked ECC matrices degraded within 6 h when treated
      with collagenase, EDC-NHS or genipin crosslinking significantly improved the
      stability of ECC matrices (192 h for EDC-NHS and 256 h for genipin). Results from
      the mechanical tests showed that both EDC-NHS and genipin crosslinking
      significantly improved the strength and modulus of ECC matrices. Cell culture
      studies showed that keratocyte cell viability and proliferation are maintained on
      EDC-NHS crosslinked ECC matrices. Overall, results from this study suggest that
      ECC matrices have the potential to be developed as a functional biomaterial for
      corneal repair and regeneration.

PMID- 27710924
TI  - Gruneisen parameter studies on heavy fermion quantum criticality.
AB  - The Gruneisen parameter, experimentally determined from the ratio of thermal
      expansion to specific heat, quantifies the pressure dependence of characteristic
      energy scales of matter. It is highly enhanced for Kondo lattice systems, whose
      properties are strongly dependent on the pressure sensitive antiferromagnetic
      exchange interaction between f- and conduction electrons. In this review, we
      focus on the divergence of the Gruneisen parameter and its magnetic analogue, the
      adiabatic magnetocaloric effect, for heavy-fermion metals near quantum critical
      points. We compare experimental results with current theoretical models,
      including the effect of strong geometrical frustration. We also discuss the
      possibility of using materials with the divergent magnetic Gruneisen parameter
      for adiabatic demagnetization cooling to very low temperatures.

PMID- 27710925
TI  - Curcumin eluting nanofibers augment osteogenesis toward phytochemical based bone
      tissue engineering.
AB  - Curcumin is a phenolic compound isolated from Curcuma longa that is known to
      exhibit wide ranging biological activity including potential benefits for bone
      growth. The aim of this work was to engineer curcumin eluting tissue scaffolds
      and investigate their potential use in bone tissue regeneration. We prepared
      curcumin loaded poly(epsilon-caprolactone) (PCL) nanofibers by electrospinning.
      Morphological characterization of the nanofibers revealed that the average
      diameter of neat fibers and that of fibers with 1 wt% and 5 wt% curcumin is 840 
      +/-  130 nm, 827  +/-  129 nm and 680  +/-  110 nm, respectively. Fourier
      transformation infrared spectroscopy and 1H nuclear magnetic resonance confirmed
      the successful loading of the drug in fibers. In aqueous medium, the fibers
      released  ~18% of the encapsulated drug in 3 d and  ~60% in 9 d. The cell
      response to the curcumin loaded nanofibers was assessed using MC3T3-E1 pre
      osteoblasts. Cell proliferation was moderated with increased loading of curcumin
      and was 50% lower on the fibers containing 5% curcumin at day 10 than the control
      fibers. Osteogenesis was confirmed by assaying the expression of alkaline
      phosphatase and staining of mineral deposits by Alizarin red stain, which were
      both markedly higher for 1% curcumin compared to neat polymer but lower for 5%
      curcumin. Mineral deposition was also confirmed chemically by Fourier transform
      infrared spectroscopy. These results were corroborated by increased gene and
      protein expression of known osteogenic markers in 1% curcumin. Thus, controlled
      release of curcumin from polymer scaffolds is a promising strategy for bone
      tissue regeneration.

PMID- 27710926
TI  - Collective responses of a large mackerel school depend on the size and speed of a
      robotic fish but not on tail motion.
AB  - So far, actuated fish models have been used to study animal interactions in small
      scale controlled experiments. This study, conducted in a semi-controlled setting,
      investigates robot5 interactions with a large wild-caught marine fish school
      (~3000 individuals) in their natural social environment. Two towed fish robots
      were used to decouple size, tail motion and speed in a series of sea-cage
      experiments. Using high-resolution imaging sonar and sonar-video blind scoring,
      we monitored and classified the school's collective reaction towards the fish
      robots as attraction or avoidance. We found that two key releasers-the size and
      the speed of the robotic fish-were responsible for triggering either evasive
      reactions or following responses. At the same time, we found fish reactions to
      the tail motion to be insignificant. The fish evaded a fast-moving robot even if
      it was small. However, mackerels following propensity was greater towards a slow
      small robot. When moving slowly, the larger robot triggered significantly more
      avoidance responses than a small robot. Our results suggest that the collective
      responses of a large school exposed to a robotic fish could be manipulated by
      tuning two principal releasers-size and speed. These results can help to design
      experimental methods for in situ observations of wild fish schools or to develop
      underwater robots for guiding and interacting with free-ranging aggregated
      aquatic organisms.

PMID- 27710927
TI  - Biomacromolecule immobilization: grafting of fish-scale collagen peptides onto
      aminolyzed P(3HB-co-4HB) scaffolds as a potential wound dressing.
AB  - Polyhydroxyalkanoate (PHA) is a microbial polymer that has been at the forefront
      of many attempts at tissue engineering. However, the surface of poly(3
      hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) is hydrophobic with few
      recognition sites for cell attachment. Various concentrations of fish-scale
      collagen peptides (FSCPs) were incorporated into P(3HB-co-4HB) copolymer by
      aminolysis. Later, FSCPs were introduced onto the aminolyzed P(3HB-co-4HB)
      scaffolds. Introduction of the FSCP groups was verified using Fourier transform
      infrared spectroscopy and the ninhydrin method. The effect of the incorporation
      of FSCPs on hydrophilicity was investigated using the water contact angle. As the
      concentration of FSCPs increased, the water contact angle decreased. In vitro
      study demonstrated that P(3HB-co-4HB)/FSCP scaffolds provided better cell
      attachment and growth of L929 mouse fibroblast cells and better cell
      proliferation. In vivo study showed that P(3HB-co-4HB)/1.5 wt% FSCPs had a
      significant effect on wound contractions, with the highest percentage of wound
      closure (61%) in 7 d.

PMID- 27710928
TI  - In vivo neutron activation study of the short-term kinetic behaviour of sodium
      and chlorine in the human hand.
AB  - The time-dependent behaviour of sodium and chlorine was studied as a spinoff from
      a study of aluminum in the hand of subjects suffering from Alzheimer's disease
      and a control group, involving 15 Alzheimer's and 16 control subjects with an age
      range of 63-89 years. This was achieved using the in vivo neutron activation
      analysis system developed at McMaster University for the non-invasive measurement
      of aluminum, where a subject's hand is placed in a beam of accelerator-based
      thermalized neutrons, which activates elements by neutron capture. Following
      irradiation, the subject's hand is placed in a detection system comprising 9
      NaI(Tl) detectors arranged in a 4pi geometry to measure activated elements. The
      redistribution half-lives of the activation products 24Na and 38Cl from the hand
      were determined after correction for the physical half-life, by means of
      sequential analysis of the residual activity in the hand. The kinetic behaviours
      of sodium and chlorine were best characterized by an exponential function
      corresponding to the rapidly exchangeable pool. The mean redistribution half
      lives from the hand for sodium and chlorine in the control subjects were 40.5  +/
      17.4 min and 24.2  +/-  8.5 min, respectively. For Alzheimer's disease subjects
      the mean redistribution half-lives were 58.2  +/-  36.1 min for sodium and 33.6 
      +/-  16.7 min for chlorine. There was no significant difference in chlorine and
      sodium redistribution half-lives between the Alzheimer's disease and control
      group subjects. These results are promising, given that the irradiation and
      counting protocol were optimized for the aluminum study, rendering them
      suboptimal for analyzing other elements and their rate of change with time.
      Further improvements include optimizing the irradiation protocol, longer counting
      times, and measuring the activity in the un-irradiated hand in various time
      intervals following irradiation.

PMID- 27710929
TI  - Determination of crystal structures of proteins of unknown identity using a
      marathon molecular replacement procedure: structure of Stenotrophomonas
      maltophilia phosphate-binding protein.
AB  - During the past decade, the authors have collected a few X-ray diffraction data
      sets from protein crystals that appeared to be easy cases of molecular
      replacement but failed to yield structures even after extensive trials. Here, the
      use of a large-scale molecular replacement method that explores all structurally
      characterized domains as phasing models to determine the structure corresponding
      to two data sets collected at 1.9 and 2.3 A resolution is reported. These two
      structures were of the same protein independently crystallized in 2007 and 2011.
      The structures derived are virtually identical and were found to consist of two
      compact globular domains connected by a hinge. The high resolution of one of
      these data sets enabled inference of the amino-acid sequence from the electron
      density map. The deduced sequence is nearly identical to that of a protein from
      the multidrug-resistant bacterium Stenotrophomonas maltophilia. Although the
      structure of this protein has not been determined previously, it is homologous to
      the well studied DING proteins which mediate the cellular uptake of phosphate
      ions. The final electron-density maps from both of the data sets revealed a large
      density at the interface of the two globular domains that is likely to represent
      a phosphate ion. Thus, the structure is likely to be that of a phosphate-binding
      protein encoded by the S. maltophilia genome (SmPBP; PDB entry 5j1d). The nature
      of the phosphate-binding site of SmPBP closely resembles that of Pseudomonas
      fluorescens DING (PfluDING), which displays remarkable discrimination between the
      closely similar phosphate and arsenate ions. The results presented here
      illustrate that routine crystallization trials may occasionally lead to the
      serendipitous crystallization of a protein of unknown identity and brute-force
      molecular replacement through 'fold space' might allow the identification of the
      unknown protein.

PMID- 27710930
TI  - Online ion-exchange chromatography for small-angle X-ray scattering.
AB  - Biological small-angle X-ray scattering (BioSAXS) is a powerful technique to
      determine the solution structure, particle size, shape and surface-to-volume
      ratio of macromolecules. However, a drawback is that the sample needs to be
      monodisperse. To ensure this, size-exclusion chromatography (SEC) has been
      implemented on many BioSAXS beamlines. Here, the integration of ion-exchange
      chromatography (IEC) using both continuous linear and step gradients on a
      beamline is described. Background subtraction for continuous gradients by
      shifting a reference measurement and two different approaches for step gradients,
      which are based on interpolating between two background measurements, are
      discussed. The results presented here serve as a proof of principle for online
      IEC and subsequent data treatment.

PMID- 27710931
TI  - Crystal structures of the disulfide reductase DsbM from Pseudomonas aeruginosa.
AB  - In bacteria, many Dsb-family proteins play diverse roles in the conversion
      between the oxidized and reduced states of cysteine residues of substrate
      proteins. Most Dsb enzymes catalyze disulfide formation in periplasmic or
      secreted substrate proteins. Recently, a DsbM protein has been found in a Gram
      negative bacterium, and was characterized as a cytosolic Dsb member with the
      conserved CXXC motif on the basis of sequence homology to the Dsb-family
      proteins. The protein was implicated in the reduction of the cytoplasmic redox
      sensor protein OxyR in Pseudomonas aeruginosa. Here, crystal structures of DsbM
      from P. aeruginosa are presented, revealing that it consists of a modified
      thioredoxin domain containing the CXXC motif and a lid domain surrounding the
      CXXC motif. In a glutathione-linked structure, a glutathione molecule is linked
      to the CXXC motif of DsbM and is bound in an elongated cavity region in the
      thioredoxin domain, which is also suited for substrate peptide binding. A
      striking structural similarity to a human glutathione S-transferase was found in
      the glutathione-binding pocket. Further, biochemical evidence is presented
      suggesting that DsbM is directly involved in the reduction of the disulfide of
      Cys199 and Cys208 in OxyR, resulting in the acceleration of OxyR reduction in the
      absence of reactive oxygen species stress. These findings may help to expand the
      understanding of the diverse roles of redox-related proteins that contain the
      CXXC motif.

PMID- 27710932
TI  - Validation and correction of Zn-CysxHisy complexes.
AB  - Many crystal structures in the Protein Data Bank contain zinc ions in a
      geometrically distorted tetrahedral complex with four Cys and/or His ligands. A
      method is presented to automatically validate and correct these zinc complexes.
      Analysis of the corrected zinc complexes shows that the average Zn-Cys distances
      and Cys-Zn-Cys angles are a function of the number of cysteines and histidines
      involved. The observed trends can be used to develop more context-sensitive
      targets for model validation and refinement.

PMID- 27710933
TI  - Empirical power laws for the radii of gyration of protein oligomers.
AB  - The radius of gyration is a fundamental structural parameter that is particularly
      useful for describing polymers. It has been known since Flory's seminal work in
      the mid-20th century that polymers show a power-law dependence, where the radius
      of gyration is proportional to the number of residues raised to a power. The
      power-law exponent has been measured experimentally for denatured proteins and
      derived empirically for folded monomeric proteins using crystal structures. Here,
      the biological assemblies in the Protein Data Bank are surveyed to derive the
      power-law parameters for protein oligomers having degrees of oligomerization of 2
      6 and 8. The power-law exponents for oligomers span a narrow range of 0.38-0.41,
      which is close to the value of 0.40 obtained for monomers. This result shows that
      protein oligomers exhibit essentially the same power-law behavior as monomers. A
      simple power-law formula is provided for estimating the oligomeric state from an
      experimental measurement of the radius of gyration. Several proteins in the
      Protein Data Bank are found to deviate substantially from power-law behavior by
      having an atypically large radius of gyration. Some of the outliers have highly
      elongated structures, such as coiled coils. For coiled coils, the radius of
      gyration does not follow a power law and instead scales linearly with the number
      of residues in the oligomer. Other outliers are proteins whose oligomeric state
      or quaternary structure is incorrectly annotated in the Protein Data Bank. The
      power laws could be used to identify such errors and help prevent them in future
      depositions.

PMID- 27710934
TI  - Manipulation of an existing crystal form unexpectedly results in interwoven
      packing networks with pseudo-translational symmetry.
AB  - Nonribosomal peptide synthetases (NRPSs) are multimodular enzymes that synthesize
      a myriad of diverse molecules. Tailoring domains have been co-opted into NRPSs to
      introduce further variety into nonribosomal peptide products. Linear gramicidin
      synthetase contains a unique formylation-tailoring domain in its initiation
      module (F-A-PCP). The structure of the F-A di-domain has previously been
      determined in a crystal form which had large solvent channels and no density for
      the minor Asub subdomain. An attempt was made to take advantage of this packing
      by removing the Asub subdomain from the construct (F-ADeltasub) in order to
      produce a crystal that could accommodate the PCP domain. In the resulting crystal
      the original packing network was still present, but a second network with the
      same packing and almost no contact with the original network took the place of
      the solvent channels and changed the space group of the crystal.

PMID- 27710935
TI  - PRISM-EM: template interface-based modelling of multi-protein complexes guided by
      cryo-electron microscopy density maps.
AB  - The structures of protein assemblies are important for elucidating cellular
      processes at the molecular level. Three-dimensional electron microscopy (3DEM) is
      a powerful method to identify the structures of assemblies, especially those that
      are challenging to study by crystallography. Here, a new approach, PRISM-EM, is
      reported to computationally generate plausible structural models using a
      procedure that combines crystallographic structures and density maps obtained
      from 3DEM. The predictions are validated against seven available structurally
      different crystallographic complexes. The models display mean deviations in the
      backbone of <5 A. PRISM-EM was further tested on different benchmark sets; the
      accuracy was evaluated with respect to the structure of the complex, and the
      correlation with EM density maps and interface predictions were evaluated and
      compared with those obtained using other methods. PRISM-EM was then used to
      predict the structure of the ternary complex of the HIV-1 envelope glycoprotein
      trimer, the ligand CD4 and the neutralizing protein m36.

PMID- 27710936
TI  - Automated refinement of macromolecular structures at low resolution using prior
      information.
AB  - Since the ratio of the number of observations to adjustable parameters is small
      at low resolution, it is necessary to use complementary information for the
      analysis of such data. ProSMART is a program that can generate restraints for
      macromolecules using homologous structures, as well as generic restraints for the
      stabilization of secondary structures. These restraints are used by REFMAC5 to
      stabilize the refinement of an atomic model. However, the optimal refinement
      protocol varies from case to case, and it is not always obvious how to select
      appropriate homologous structure(s), or other sources of prior information, for
      restraint generation. After running extensive tests on a large data set of low
      resolution models, the best-performing refinement protocols and strategies for
      the selection of homologous structures have been identified. These strategies and
      protocols have been implemented in the Low-Resolution Structure Refinement
      (LORESTR) pipeline. The pipeline performs auto-detection of twinning and selects
      the optimal scaling method and solvent parameters. LORESTR can either use user
      supplied homologous structures, or run an automated BLAST search and download
      homologues from the PDB. The pipeline executes multiple model-refinement
      instances using different parameters in order to find the best protocol. Tests
      show that the automated pipeline improves R factors, geometry and Ramachandran
      statistics for 94% of the low-resolution cases from the PDB included in the test
      set.

PMID- 27710937
TI  - Crystal structure of yeast monothiol glutaredoxin Grx6 in complex with a
      glutathione-coordinated [2Fe-2S] cluster.
AB  - Glutaredoxins (Grxs) constitute a superfamily of proteins that perform diverse
      biological functions. The Saccharomyces cerevisiae glutaredoxin Grx6 not only
      serves as a glutathione (GSH)-dependent oxidoreductase and as a GSH transferase,
      but also as an essential [2Fe-2S]-binding protein. Here, the dimeric structure of
      the C-terminal domain of Grx6 (holo Grx6C), bridged by one [2Fe-2S] cluster
      coordinated by the active-site Cys136 and two external GSH molecules, is
      reported. Structural comparison combined with multiple-sequence alignment
      demonstrated that holo Grx6C is similar to the [2Fe-2S] cluster-incorporated
      dithiol Grxs, which share a highly conserved [2Fe-2S] cluster-binding pattern and
      dimeric conformation that is distinct from the previously identified [2Fe-2S]
      cluster-ligated monothiol Grxs.

PMID- 27710938
TI  - Arabidopsis receptor-like cytoplasmic kinase BIK1: purification, crystallization
      and X-ray diffraction analysis.
AB  - Receptor-like cytoplasmic kinases (RLCKs) in Arabidopsis play a central role in
      the integration of signaling input from various growth and immune signaling
      pathways. BOTRYTIS-INDUCED KINASE 1 (BIK1), belonging to the RLCK family, is an
      important player in defense against bacterial and fungal pathogens and in
      ethylene and brassinosteroid hormone signaling. In this study, the purification
      and crystallization of a first member of the class VI family of RLCK proteins,
      BIK1, are reported. BIK1 was crystallized using the microbatch-under-oil method.
      X-ray diffraction data were collected to 2.35 A resolution. The crystals belonged
      to the monoclinic space group C2, with two monomers per asymmetric unit.

PMID- 27710939
TI  - Crystal and solution structural studies of mouse phospholipid hydroperoxide
      glutathione peroxidase 4.
AB  - The mammalian glutathione peroxidase (GPx) family is a key component of the
      cellular antioxidative defence system. Within this family, GPx4 has unique
      features as it accepts a large class of hydroperoxy lipid substrates and has a
      plethora of biological functions, including sperm maturation, regulation of
      apoptosis and cerebral embryogenesis. In this paper, the structure of the
      cytoplasmic isoform of mouse phospholipid hydroperoxide glutathione peroxidase
      (O70325-2 GPx4) with selenocysteine 46 mutated to cysteine is reported solved at
      1.8 A resolution using X-ray crystallography. Furthermore, solution data of an
      isotope-labelled GPx protein are presented.

PMID- 27710940
TI  - The structure of a glycoside hydrolase 29 family member from a rumen bacterium
      reveals unique, dual carbohydrate-binding domains.
AB  - Glycoside hydrolase (GH) family 29 consists solely of alpha-L-fucosidases. These
      enzymes catalyse the hydrolysis of glycosidic bonds. Here, the structure of
      GH29_0940, a protein cloned from metagenomic DNA from the rumen of a cow, has
      been solved, which reveals a multi-domain arrangement that has only recently been
      identified in bacterial GH29 enzymes. The microbial species that provided the
      source of this enzyme is unknown. This enzyme contains a second carbohydrate
      binding domain at its C-terminal end in addition to the typical N-terminal
      catalytic domain and carbohydrate-binding domain arrangement of GH29-family
      proteins. GH29_0940 is a monomer and its overall structure consists of an N
      terminal TIM-barrel-like domain, a central beta-sandwich domain and a C-terminal
      beta-sandwich domain. The TIM-barrel-like catalytic domain exhibits a
      (beta/alpha)8/7 arrangement in the core instead of the typical (beta/alpha)8
      topology, with the 'missing' alpha-helix replaced by a long meandering loop that
      'closes' the barrel structure and suggests a high degree of structural
      flexibility in the catalytic core. This feature was also noted in all six other
      structures of GH29 enzymes that have been deposited in the PDB. Based on sequence
      and structural similarity, the residues Asp162 and Glu220 are proposed to serve
      as the catalytic nucleophile and the proton donor, respectively. Like other GH29
      enzymes, the GH29_0940 structure shows five strictly conserved residues in the
      catalytic pocket. The structure shows two glycerol molecules in the active site,
      which have also been observed in other GH29 structures, suggesting that the
      enzyme catalyses the hydrolysis of small carbohydrates. The two binding domains
      are classed as family 32 carbohydrate-binding modules (CBM32). These domains have
      residues involved in ligand binding in the loop regions at the edge of the beta
      sandwich. The predicted substrate-binding residues differ between the modules,
      suggesting that different modules bind to different groups on the substrate(s).
      Enzymes that possess multiple copies of CBMs are thought to have a complex
      mechanism of ligand recognition. Defined electron density identifying a long 20
      amino-acid hydrophilic loop separating the two CBMs was observed. This suggests
      that the additional C-terminal domain may have a dynamic range of movement
      enabled by the loop, allowing a unique mode of action for a GH29 enzyme that has
      not been identified previously.

PMID- 27710941
TI  - Comparative analysis of anti-polyglutamine Fab crystals grown on Earth and in
      microgravity.
AB  - Huntington's disease is one of nine neurodegenerative diseases caused by a
      polyglutamine (polyQ)-repeat expansion. An anti-polyQ antigen-binding fragment,
      MW1 Fab, was crystallized both on Earth and on the International Space Station, a
      microgravity environment where convection is limited. Once the crystals returned
      to Earth, the number, size and morphology of all crystals were recorded, and X
      ray data were collected from representative crystals. The results generally
      agreed with previous microgravity crystallization studies. On average,
      microgravity-grown crystals were 20% larger than control crystals grown on Earth,
      and microgravity-grown crystals had a slightly improved mosaicity (decreased by
      0.03 degrees ) and diffraction resolution (decreased by 0.2 A) compared with
      control crystals grown on Earth. However, the highest resolution and lowest
      mosaicity crystals were formed on Earth, and the highest-quality crystal overall
      was formed on Earth after return from microgravity.

PMID- 27710942
TI  - Crystal structure of rofecoxib bound to human cyclooxygenase-2.
AB  - Rofecoxib (Vioxx) was one of the first selective cyclooxygenase-2 (COX-2)
      inhibitors (coxibs) to be approved for use in humans. Within five years after its
      release to the public, Vioxx was withdrawn from the market owing to the adverse
      cardiovascular effects of the drug. Despite the widespread knowledge of the
      development and withdrawal of Vioxx, relatively little is known at the molecular
      level about how the inhibitor binds to COX-2. Vioxx is unique in that the
      inhibitor contains a methyl sulfone moiety in place of the sulfonamide moiety
      found in other coxibs such as celecoxib and valdecoxib. Here, new crystallization
      conditions were identified that allowed the structural determination of human COX
      2 in complex with Vioxx and the structure was subsequently determined to 2.7 A
      resolution. The crystal structure provides the first atomic level details of the
      binding of Vioxx to COX-2. As anticipated, Vioxx binds with its methyl sulfone
      moiety located in the side pocket of the cyclooxygenase channel, providing
      support for the isoform selectivity of this drug.

PMID- 27710943
TI  - Crystallographic study of the 2-thioribothymidine-synthetic complex TtuA-TtuB
      from Thermus thermophilus.
AB  - The ubiquitin-like protein TtuB is a sulfur carrier for the biosynthesis of 2
      thioribothymidine (s2T) at position 54 in some thermophilic bacterial tRNAs. TtuB
      captures a S atom at its C-terminus as a thiocarboxylate and transfers it to tRNA
      by the transferase activity of TtuA. TtuB also functions to suppress s2T
      formation by forming a covalent bond with TtuA. To explore how TtuB interacts
      with TtuA and switches between these two different functions, high-resolution
      structure analysis of the TtuA-TtuB complex is required. In this study, the TtuA
      TtuB complex from Thermus thermophilus was expressed, purified and crystallized.
      To mimic the thiocarboxylated TtuB, the C-terminal Gly residue was replaced with
      Cys (G65C) to obtain crystals of the TtuA-TtuB complex. A Zn-MAD data set was
      collected to a resolution of 2.5 A. MAD analysis successfully determined eight Zn
      sites, and a partial structure model composed of four TtuA-TtuB complexes in the
      asymmetric unit was constructed.

PMID- 27710945
TI  - Biochemical, spectroscopic and X-ray structural analysis of deuterated
      multicopper oxidase CueO prepared from a new expression construct for neutron
      crystallography.
AB  - Multicopper oxidases oxidize various phenolic and nonphenolic compounds by using
      molecular oxygen as an electron acceptor to produce water. A multicopper oxidase
      protein, CueO, from Escherichia coli is involved in copper homeostasis in the
      bacterial cell. Although X-ray crystallographic studies have been conducted, the
      reduction mechanism of oxygen and the proton-transfer pathway remain unclear
      owing to the difficulty in identifying H atoms from X-ray diffraction data alone.
      To elucidate the reaction mechanism using neutron crystallography, a preparation
      system for obtaining large, high-quality single crystals of deuterated CueO was
      developed. Tiny crystals were obtained from the deuterated CueO initially
      prepared from the original construct. The X-ray crystal structure of the
      deuterated CueO showed that the protein contained an incompletely truncated
      signal sequence at the N-terminus, which resulted in the heterogeneity of the
      protein sample for crystallization. Here, a new CueO expression system that had
      an HRV3C cleavage site just after the signal sequence was constructed. Deuterated
      CueO from the new construct was expressed in cells cultured in deuterated algae
      extract medium and the signal sequence was completely eliminated by HRV3C
      protease. The deuteration level of the purified protein was estimated by MALDI
      TOF mass spectrometry to be at least 83.2% compared with nondeuterated protein.
      Nondeuterated CueO crystallized in space group P21, with unit-cell parameters a =
      49.51, b = 88.79, c = 53.95 A, beta = 94.24 degrees , and deuterated CueO
      crystallized in space group P212121, with unit-cell parameters a = 49.91, b =
      106.92, c = 262.89 A. The crystallographic parameters for the crystals of the new
      construct were different from those previously reported for nondeuterated
      crystals. The nondeuterated and deuterated CueO from the new construct had
      similar UV-Vis spectra, enzymatic activities and overall structure and geometry
      of the ligands of the Cu atoms in the active site to those of previously reported
      CueO structures. These results indicate that the CueO protein prepared using the
      new construct is suitable for further neutron diffraction studies.

PMID- 27710944
TI  - X-ray crystallographic studies of the extracellular domain of the first plant ATP
      receptor, DORN1, and the orthologous protein from Camelina sativa.
AB  - Does not respond to nucleotides 1 (DORN1) has recently been identified as the
      first membrane-integral plant ATP receptor, which is required for ATP-induced
      calcium response, mitogen-activated protein kinase activation and defense
      responses in Arabidopsis thaliana. In order to understand DORN1-mediated ATP
      sensing and signal transduction, crystallization and preliminary X-ray studies
      were conducted on the extracellular domain of DORN1 (atDORN1-ECD) and that of an
      orthologous protein, Camelina sativa lectin receptor kinase I.9 (csLecRK-I.9-ECD
      or csI.9-ECD). A variety of deglycosylation strategies were employed to optimize
      the glycosylated recombinant atDORN1-ECD for crystallization. In addition, the
      glycosylated csI.9-ECD protein was crystallized at 291 K. X-ray diffraction data
      were collected at 4.6 A resolution from a single crystal. The crystal belonged to
      space group C222 or C2221, with unit-cell parameters a = 94.7, b = 191.5, c =
      302.8 A. These preliminary studies have laid the foundation for structural
      determination of the DORN1 and I.9 receptor proteins, which will lead to a better
      understanding of the perception and function of extracellular ATP in plants.

PMID- 27710947
TI  - Bone Augmentation Through Orthodontic Movement.

PMID- 27710948
TI  - T-Scan Occlusal Analysis After Adult Orthodontic Treatment.

PMID- 27710946
TI  - Expression and crystallographic studies of the Arabidopsis thaliana GDP-D-mannose
      pyrophosphorylase VTC1.
AB  - GDP-D-mannose pyrophosphorylase catalyzes the production of GDP-D-mannose, an
      intermediate product in the plant ascorbic acid (AsA) biosynthetic pathway. This
      enzyme is a key regulatory target in AsA biosynthesis and is encoded by VITAMIN C
      DEFECTIVE 1 (VTC1) in the Arabidopsis thaliana genome. Here, recombinant VTC1 was
      expressed, purified and crystallized. Diffraction data were obtained from VTC1
      crystals grown in the absence and presence of substrate using X-rays. The ligand
      free VTC1 crystal diffracted X-rays to 3.3 A resolution and belonged to space
      group R32, with unit-cell parameters a = b = 183.6, c = 368.5 A, alpha = beta =
      90, gamma = 120 degrees ; the crystal of VTC1 in the presence of substrate
      diffracted X-rays to 1.75 A resolution and belonged to space group P21, with unit
      cell parameters a = 70.8, b = 83.9, c = 74.5 A, alpha = gamma = 90.0, beta =
      114.9 degrees .

PMID- 27710949
TI  - Rapid Maxillary Expansion and Upper-Molar Distalization with a Miniscrew
      Supported Hybrid Appliance.

PMID- 27710950
TI  - Predictability of Orthodontic Forced Eruption in Developing an Implant Site: A
      Systematic Review.

PMID- 27710951
TI  - Correction of Unilateral Complete Buccal Crossbite with Miniscrew Anchorage.

PMID- 27710953
TI  - In-Office Fabrication of a Flipper.

PMID- 27710952
TI  - An Innovative Tucker for the SmartClip System.

PMID- 27710954
TI  - Uprighting and Periodontally Accelerated Osteogenic Orthodontics as an
      Alternative to Surgical Crown Lengthening.

PMID- 27710955
TI  - Morphological Variation of Subarcuate Artery and Canal in Atresia.
AB  - OBJECTIVES: An aberrant subarcuate artery (SAA) and its related canal are
      infrequent and asymptomatic. The presence of this variation may cause untoward
      hemorrhages, if accidentally nicked. Therefore, it is important for otologists to
      be aware of this entity, and its relative anatomy, to avoid any unexpected
      complication. We present a case of a 7-year-old girl who presented with right
      sided microtia with membranous atresia. METHODS: High-resolution computed
      tomographic scan and three-dimensional reconstruction of the temporal bone showed
      bilateral enlarged SAA. RESULTS: The width of the right-sided bone canal was
      between 0.76 and 1.33 mm. The left temporal bone showed the same variation, with
      the width of the canal consistently greater than 1.0 mm, ranging from 1.07 to
      1.23 mm in greatest transverse dimension. CONCLUSIONS: The variation proposed in
      microtia was not previously reported in the literature, which may have important
      implications for the canal reconstruction.

PMID- 27710956
TI  - Interstitial NORs, Fragile Sites, and Chromosome Evolution: A Not So Simple
      Relationship - The Example of Melolontha melolontha and Genus Protaetia
      (Coleoptera: Scarabaeidae).
AB  - In the present study, the origin of recurrent rearrangements involving chromosome
      6 in 3.2% of cells of Melolontha melolontha (Coleoptera, Scarabaeidae) was
      investigated. Various chromosome staining techniques, including C-banding, Giemsa
      and silver staining, as well as fluorescence in situ hybridization with a human
      28S rDNA probe, were applied to M. melolontha chromosome spreads. In addition,
      related species of the genera Melolontha and Protaetia were studied. On
      chromosome 6 of M. melolontha, there is a fragile site-like structure which
      corresponds to an interstitial nucleolus organizer region (NOR). Despite this
      instability, the NOR remains unique and interstitial in this species, as well as
      in the other species studied. It is proposed that the intercalary position of the
      NOR both facilitates the detection of its fragile site-like instability and
      correlates with its relative stability during evolution. We explain this apparent
      paradox by strong counter-selection for imbalances of the chromosome fragment
      distal to the interstitial NORs, which would recurrently occur in the progeny of
      translocation carriers. Thus, the frequent telomeric position of the NORs in most
      animal and plant taxa would have no functional rationale but would be the
      consequence of selection against the meiotic transmission of chromosome
      imbalances.

PMID- 27710957
TI  - Translocation (9;12)(q34.1;p13.?3) Resulted in ETV6-ABL1 Fusion in a Patient with
      Philadelphia Chromosome-Negative Chronic Myelogenous Leukemia.

PMID- 27710958
TI  - Karyotype and Mapping of Repetitive DNAs in the African Butterfly Fish Pantodon
      buchholzi, the Sole Species of the Family Pantodontidae.
AB  - The monophyletic order Osteoglossiformes represents one of the most ancestral
      groups of teleosts and has at least 1 representative in all continents of the
      southern hemisphere, with the exception of Antarctica. However, despite its
      phylogenetic and biogeographical importance, cytogenetic data in
      Osteoglossiformes are scarce. Here, karyotype and chromosomal characteristics of
      the lower Niger River population of the African butterfly fish Pantodon
      buchholzi, the sole species of the family Pantodontidae (Osteoglossiformes), were
      examined using conventional and molecular cytogenetic approaches. All specimens
      examined had 2n = 46 chromosomes, with a karyotype composed of 5 pairs of
      metacentric, 5 pairs of submetacentric, and 13 pairs of acrocentric chromosomes
      in both sexes. No morphologically differentiated sex chromosomes were identified.
      C-bands were located in the centromeric/pericentromeric region of all chromosomes
      and were associated with the single AgNOR site. FISH with ribosomal DNA probes
      revealed that both 5S and 18S rDNA were present in only 1 pair of chromosomes
      each, but did not colocalize. CMA3+ bands were observed near the telomeres in
      several chromosome pairs and also at the 18S rDNA sites. The mapping of di- and
      trinucleotide repeat motifs, Rex6 transposable element, and U2 snRNA showed a
      scattered distribution over most of the chromosomes, but for some microsatellites
      and the U2 snRNA also a preferential accumulation at telomeric regions. This
      study presents the first detailed cytogenetic analysis in the African butterfly
      fish by both conventional and molecular cytogenetic protocols. This is the first
      of a series of further cytogenetic and cytogenomic studies on osteoglossiforms,
      aiming to comprehensively examine the chromosomal evolution in this
      phylogenetically important fish order.

PMID- 27710959
TI  - Attenuated Heart Rate Recovery in Mercury-Exposed Individuals.

PMID- 27710961
TI  - Abstracts of the 13th Annual ENETS Conference for the Diagnosis and Treatment of
      Neuroendocrine Tumor Disease. March 9-11, 2016, Barcelona, Spain: Abstracts.

PMID- 27710960
TI  - Molecular Understanding of Non-Transfusion-Dependent Thalassemia Associated with
      Hemoglobin E-beta-Thalassemia in Northeast Thailand.
AB  - Non-transfusion-dependent thalassemia (NTDT) is associated with various forms of
      thalassemia and genetic modifiers. We report the molecular basis of NTDT in
      hemoglobin (Hb) E-beta-thalassemia disease. This study was done in 73 adult
      patients encountered at the prenatal diagnosis center of Khon Kaen University,
      Northeast Thailand. Hematological parameters and Hb patterns were collected, and
      alpha- and beta-globin gene mutations were determined. Multiple single-nucleotide
      polymorphisms (SNPs) including the rs7482144/Ggamma-XmnI polymorphism, rs2297339,
      rs2838513, rs4895441, and rs9399137 in the HBS1L-MYB gene, rs4671393 and
      rs11886868 in the BCL11A gene, and G176AfsX179 in the KLF1 gene were examined.
      Five beta0-thalassemia mutations and a severe beta+-thalassemia mutation in trans
      to the betaE gene were identified. No significant difference in hematological
      parameters was observed among beta-thalassemia genotypes. Coinheritance of alpha
      thalassemia was observed in 31 of the 73 subjects (42.5%). Four SNPs including
      Ggamma-XmnI, rs2297339, rs4895441, and rs9399137 of HBS1L-MYB were found to be
      associated with high Hb F levels in 39 (53.4%) subjects. The molecular basis of
      NTDT in the remaining 3 (4.1%) cases could not be defined. These results indicate
      multiple genetic factors in NTDT patients and underline the importance of
      complete genotyping to provide proper management, make clinical predictions, and
      improve genetic counseling.

PMID- 27710962
TI  - Voltage-Gated Potassium Channel Antibodies in Slow-Progression Motor Neuron
      Disease.
AB  - BACKGROUND: The spectrum of autoimmune neurological diseases associated with
      voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from
      peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC
      complex Abs have also been reported in neurodegenerative disorders, but their
      clinical relevance is unknown. OBJECTIVE: The aim of the study was to explore the
      prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND).
      METHODS: We compared 11 patients affected by slow-progression MND with 9 patients
      presenting typical progression illness. Sera were tested for VGKC-complex Abs by
      radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann
      Whitney U test. RESULTS: The statistical analysis showed a significant difference
      between the mean values in the study and control groups. A case with long
      survival MND harboring VGKC-complex Abs and treated with intravenous
      immunoglobulins is described. CONCLUSION: Although VGKC-complex Abs are not
      likely to be pathogenic, these results could reflect the coexistence of an
      immunological activation in patients with slow disease progression.

PMID- 27710963
TI  - Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and
      Prenatally Androgenized Female Mice.
AB  - BACKGROUND/AIMS: Arcuate nucleus (ARN) gamma-aminobutyric acid (GABA) neurons are
      implicated in many critical homeostatic mechanisms, from food intake to
      fertility. To determine the functional relevance of ARN GABA neurons, it is
      essential to define the neurotransmitters co-expressed with and potentially co
      released from ARN GABA neurons. METHODS: The present study investigated the
      expression of markers of specific signaling molecules by ARN GABA neurons in
      brain sections from male, female, and, in some cases, prenatally androgen-treated
      (PNA) female, vesicular GABA transporter (VGaT)-ires-Cre/tdTomato reporter mice.
      Immunofluorescence for kisspeptin, beta-endorphin, neuropeptide Y (NPY), tyrosine
      hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) was detected by
      confocal microscopy, and co-localization with tdTomato VGaT reporter expression
      throughout the ARN was quantified. RESULTS: GABA neurons rarely co-localized with
      kisspeptin (<2%) or beta-endorphin (<1%), and only a small proportion of
      kisspeptin (~10%) or beta-endorphin (~3%) neurons co-localized with VGaT in male
      and female mice. In contrast, one-third of ARN GABA neurons co-localized with
      NPY, and nearly all NPY neurons (>95%) co-localized with VGaT across groups. Both
      TH and nNOS labeling was co-localized with ~10% of ARN GABA neurons. The
      proportion of TH neurons co-localized with VGaT was significantly greater in
      males than either control or PNA females, and the proportion of nNOS neurons co
      localizing VGaT was higher in control and PNA females compared with males.
      CONCLUSION: These data highlight NPY as a significant subpopulation of ARN GABA
      neurons, demonstrate no significant impact of PNA on signal co-expression, and,
      for the first time, show sexually dimorphic co-expression patterns of TH and nNOS
      with ARN GABA neurons.

PMID- 27710964
TI  - Stress Effects in Vowel Perception as a Function of Language-Specific Vocabulary
      Patterns.
AB  - BACKGROUND/AIMS: Evidence from spoken word recognition suggests that for English
      listeners, distinguishing full versus reduced vowels is important, but discerning
      stress differences involving the same full vowel (as in mu- from music or museum)
      is not. In Dutch, in contrast, the latter distinction is important. This
      difference arises from the relative frequency of unstressed full vowels in the
      two vocabularies. The goal of this paper is to determine how this difference in
      the lexicon influences the perception of stressed versus unstressed vowels.
      METHODS: All possible sequences of two segments (diphones) in Dutch and in
      English were presented to native listeners in gated fragments. We recorded
      identification performance over time throughout the speech signal. The data were
      here analysed specifically for patterns in perception of stressed versus
      unstressed vowels. RESULTS: The data reveal significantly larger stress effects
      (whereby unstressed vowels are harder to identify than stressed vowels) in
      English than in Dutch. Both language-specific and shared patterns appear
      regarding which vowels show stress effects. CONCLUSION: We explain the larger
      stress effect in English as reflecting the processing demands caused by the
      difference in use of unstressed vowels in the lexicon. The larger stress effect
      in English is due to relative inexperience with processing unstressed full
      vowels.

PMID- 27710965
TI  - The Role of Biogenic Amines in the Regulation of Interaction between the Immune
      and Nervous Systems in Multiple Sclerosis.
AB  - OBJECTIVE: Multiple sclerosis (MS) is a demyelinating, presumably autoimmune
      disease of the central nervous system. Biogenic amines may participate in MS
      pathogenesis modulating immune cell activity and cytokine production. METHODS:
      Forty-three patients with relapsing-remitting MS were examined. Serotonin (SE),
      norepinephrine (NE) and epinephrine (EPI) concentrations in sera were measured by
      ELISA. The functional activity of Th17 and Th1 cells was assessed by the ability
      of peripheral blood mononuclear cells (PBMCs) to produce interferon-gamma (IFN
      gamma) and interleukin-17 (IL-17) and cell proliferation upon stimulation with
      microbeads coated with anti-CD3 and anti-CD28 antibodies. To evaluate the effect
      of biogenic amines on Th17 and Th1 cells, PBMCs were cultured in the presence of
      SE and NE. Statistical analysis was performed using Prism 6 software. RESULTS:
      Concentrations of SE and EPI in sera were not different between the groups.
      Concentrations of NE in sera from MS patients were lower than those in the
      healthy control group. The production of IL-17 and IFN-gamma in MS patients in
      relapse was higher than that in patients in remission or in the control group. SE
      at a concentration of 10-4M suppressed IL-17 production. NE at a concentration of
      10-4M suppressed both IL-17 and IFN-gamma production. CONCLUSIONS: These data
      suggest an anti-inflammatory role for biogenic amines in MS.

PMID- 27710967
TI  - Clot Formation in the Presence of Acetylsalicylic Acid Leads to Increased Lysis
      Rates Regardless of the Chosen Thrombolysis Strategy.
AB  - BACKGROUND: Patients with acute ischemic strokes frequently take an
      acetylsalicylic acid (ASA) premedication. We determined the impact of ASA on
      different thrombolysis strategies in vitro. METHODS: For two clot types made from
      platelet-rich plasma (one with and one without ASA) lysis rates were measured by
      weight loss after 1 h for five different groups: in control group A clots were
      solely placed in plasma; in groups B and C clots were treated with rt-PA (60
      kU/ml), and in groups D and E clots were treated with desmoteplase (DSPA; 2
      ug/ml). Ultrasound (2 MHz, 0.179 W/cm2) was included in groups C and E. The
      fibrin mesh structures of the clots were investigated by electron microscopy.
      RESULTS: For both clot types lysis rates increased significantly for all
      treatment strategies compared to their control group (each p < 0.001). The
      addition of ASA significantly increased the lysis rate in all 5 groups (each p <
      0.001) and led to a ceiling effect concerning the treatment. A semiquantitative
      analysis of transmission electron micrographs revealed a decreased fibrin density
      for clots with ASA. For both clot types DSPA and ultrasound led to a significant
      dissolution of the fibrin mesh (both p = 0.029). CONCLUSIONS: In vitro ASA
      pretreatment leads to significantly increased lysis rates due to a weaker fibrin
      mesh in platelet-rich plasma clots.

PMID- 27710966
TI  - Kcne4 Deletion Sex-Dependently Alters Vascular Reactivity.
AB  - Voltage-gated potassium (Kv) channels formed by Kv7 (KCNQ) alpha-subunits are
      recognized as crucial for vascular smooth muscle function, in addition to their
      established roles in the heart (Kv7.1) and the brain (Kv7.2-5). In vivo, Kv7
      alpha-subunits are often regulated by KCNE subfamily ancillary (beta) subunits.
      We investigated the effects of targeted germline Kcne4 deletion on mesenteric
      artery reactivity in adult male and female mice. Kcne4 deletion increased
      mesenteric artery contractility in response to alpha-adrenoceptor agonist
      methoxamine, and decreased responses to Kv7.2-7.5 channel activator ML213, in
      male but not female mice. In contrast, Kcne4 deletion markedly decreased
      vasorelaxation in response to isoprenaline in both male and female mice. Kcne4
      expression was 2-fold lower in the female versus the male mouse mesenteric
      artery, and Kcne4 deletion elicited only moderate changes of other Kcne
      transcripts, with no striking sex-specific differences. However, Kv7.4 protein
      expression in females was twice that in males, and was reduced in both sexes by
      Kcne4 deletion. Our findings confirm a crucial role for KCNE4 in regulation of
      Kv7 channel activity to modulate vascular tone, and provide the first known
      molecular mechanism for sex-specificity of this modulation that has important
      implications for vascular reactivity and may underlie sex-specific susceptibility
      to cardiovascular diseases.

PMID- 27710968
TI  - Endometriotic Pain Is Associated with Adenomyosis but Not with the Compartments
      Affected by Deep Infiltrating Endometriosis.
AB  - BACKGROUND: The identification of presurgical clinical markers may be helpful to
      allow the staging of endometriosis severity. It has been suggested that pain
      characteristics orientate the gynecologist about the anatomical involvement of
      endometriosis. The study was performed to analyze the correlation between pain
      symptoms and the anatomical location of endometriosis. METHODS: One hundred fifty
      five consecutive patients with a complete removal of deep infiltrating
      endometriosis (DIE) were included. Prior to surgery, data on patient and disease
      characteristics were obtained. The intensity of the pain symptoms was registered
      using a Visual Analogue Scale. The endometriotic lesions were categorized
      according to the Enzian morphological classification. Correlation and
      multivariate analysis were performed to assess the potential associations between
      pain characteristics (dysmenorrhea, pelvic pain, dyschezia, dyspareunia or
      dysuria) and the location of endometriosis or other disease-related
      characteristics (hematuria, rectal bleeding or adenomyosis). RESULTS: Pelvic pain
      was significantly associated with the presence of adenomyosis. Dyschezia was
      correlated with rectal bleeding and dysuria with the presence of hematuria. No
      relationship was found between other kinds of pain and the morphological location
      of endometriosis or other disease-related characteristics. CONCLUSION: Our data
      suggest that pelvic pain is correlated with the presence of adenomyosis in women
      with DIE. Further studies are required.

PMID- 27710969
TI  - Familial Brain Periventricular Pseudocysts.
AB  - INTRODUCTION: We report the rare finding of recurrent periventricular pseudocysts
      (PVPC) in consecutive pregnancies in 4 families and their postnatal outcome.
      MATERIALS AND METHODS: We reviewed the databases of 3 large ultrasound units
      searching for the diagnosis of PVPC in 2 pregnancies of the same patient.
      RESULTS: The first case of recurrent PVPC was diagnosed in 2011 and since then 3
      additional families were diagnosed (8 cases of PVPC all in all). All fetuses
      underwent fetal MRI that confirmed the presence of frontal or frontocaudal PVPC.
      Amniocentesis, when performed, demonstrated a normal karyotype. Termination of
      pregnancy was carried out in 2 pregnancies in 2 of 4 families. The remaining 6
      pregnancies ended with a term delivery, and to date all babies are developing
      normally. CONCLUSION: The rare finding of recurrent brain PVPC in consecutive
      pregnancies raises the possibility of a hereditary etiology as opposed to a
      sporadic event. As in isolated PVPC, frontocaudal 'familial PVPC' appears to
      carry a favorable prognosis.

PMID- 27710970
TI  - Chemotherapy in Non-Small Cell Lung Cancer Patients Receiving Oxygen Therapy.
AB  - BACKGROUND: Information regarding chemotherapy in non-small cell lung cancer
      (NSCLC) patients with chronic respiratory failure is limited. PATIENTS AND
      METHODS: We retrospectively analyzed patients who received oxygen therapy and
      underwent chemotherapy for NSCLC at our hospital. RESULTS: 6 patients with NSCLC
      receiving oxygen therapy (4 with unresectable lung cancer and 2 with
      postoperative recurrent lung cancer) underwent chemotherapy. 1 patient achieved a
      partial response and 1 achieved stable disease after first-line chemotherapy. The
      median overall survival (OS) was 247 days in all patients. Patients with
      unresectable NSCLC and recurrent NSCLC had median OS times of 282 and 239 days,
      respectively. Grade 3 lung infection occurred in 4 patients during chemotherapy
      treatment; however, there were no chemotherapy-related deaths. CONCLUSION: There
      is a possibility that chemotherapy could improve the survival of NSCLC patients
      who receive oxygen therapy.

PMID- 27710971
TI  - Prognostic Role of Lactate Dehydrogenase Expression in Urologic Cancers: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: The prognostic role of lactate dehydrogenase (LDH) in urinary system
      cancer is still controversial. Thus, we conducted a meta-analysis to assess the
      prognostic significance of LDH for patients with urinary system cancer. METHODS:
      We searched the PubMed, Embase, Springer and CNKI databases for studies published
      from January 1991 to February 2015 associated with LDH and urinary system cancer.
      Study quality was assessed using the Newcastle-Ottawa Scale. After careful
      review, survival data were extracted from eligible studies. We used pooled hazard
      ratios (HRs) to estimate the effect of LDH on overall survival (OS) and
      progression-free survival (PFS). RESULTS: 44 studies meeting the criterion were
      included. High expression of LDH was significantly correlated with poor OS in
      urologic cancer (pooled HR 1.93, 95% confidence interval (CI) 1.81-2.07; p <
      0.001). The pooled HRs showed significant difference in PFS between LDH over
      expression group with LDH low expression group (Pooled HR 1.95, 95% CI 1.61-2.36;
      p < 0.001) in urologic cancer. CONCLUSION: High serum LDH is associated with OS
      and PFS in patients with urinary system cancer, and it is an effective biomarker
      of prognosis in patients with urologic cancer.

PMID- 27710972
TI  - Survival Outcomes in EGFR Mutation-Positive Lung Cancer Patients Treated with
      Gefitinib until or beyond Progression.
AB  - BACKGROUND: Discontinuation of gefitinib treatment is often accompanied by a
      disease flare. Some studies have demonstrated a benefit of the use of epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) beyond
      progression; however, long-term results of these investigations remain limited.
      PATIENTS AND METHODS: We observed 70 patients with EGFR-mutated (EGFR-M+) non
      small cell lung cancer (NSCLC) receiving single-agent gefitinib in a routine
      clinical setting; 56 patients were experiencing RECIST progression at the time of
      the analysis. RESULTS: There was a significant increase (p = 0.00001) in overall
      survival (OS) in patients continuing on gefitinib beyond progression (n = 21;
      median duration of continued gefitinib use: 4.2 months; median OS: not reached;
      expected OS: 29.7 months) as compared to those who stopped gefitinib treatment
      upon disease progression (n = 35; median OS: 14.0 months). The association
      between extended gefitinib use and improved OS remained true in multivariate Cox
      regression analysis (hazard ratio = 4.49, 95% confidence interval 1.25-16.09; p =
      0.021). Patient selection bias constitutes an essential limitation of this
      clinical observational study, given that patients with a more favorable disease
      course and/or high initial tumor sensitivity to TKI treatment were more likely to
      be considered for prolonged gefitinib use. CONCLUSION: This study confirms that
      continued administration of gefitinib beyond progression is a viable treatment
      option for some patients with EGFR-M+ NSCLC, in particular those who cannot be
      rescued by novel EGFR mutation-specific inhibitors such as osimertinib.

PMID- 27710973
TI  - Management of Isolated Vaginal Metastasis in Squamous Cell Cervical Cancer: 23
      Years' Experience at a Single Center.
AB  - AIM: The aim of this study was to investigate the treatment options and survival
      of cervical cancer (CC) patients who develop isolated vaginal metastasis (IVM),
      and to establish risk factors for IVM. PATIENTS AND METHODS: A total of 21 cases
      with IVM were evaluated retrospectively. In addition, 42 control patients
      diagnosed with CC without recurrence were matched. Tumor size, depth of stromal
      invasion (DOI), lymphovascular space invasion (LVSI), and size of vaginal and
      lymph node metastases were analyzed in accordance with the pathology reports.
      Patients who had IVM were investigated in terms of treatment options
      (chemotherapy (CT), radiotherapy (RT), or chemoradiotherapy (CRT)) and survival.
      RESULTS: After detection of IVM, the 1-, 3-, and 5-year survival rates were 57.1,
      23.8, and 9.5%, respectively. The mean survival time after metastasis detection
      was 23.1 +/- 31.3 months. LVSI, DOI >= 1/2, hemoglobin < 12 g/dl, postmenopausal
      status, and tumor size >= 4 cm were independent risk factors for IVM. The 5-year
      survival rates were 30.0% for patients receiving RT, 17.1% for patients receiving
      CRT, and 0% for patients receiving CT. CONCLUSION: IVM typically develops within
      the first 2 years after the diagnosis of CC, and survival is generally poor. RT
      was the most effective treatment in patients with IVM.

PMID- 27710974
TI  - Increased Expression of the Receptor for Advanced Glycation End-Products (RAGE)
      Is Associated with Advanced Breast Cancer Stage.
AB  - BACKGROUND: The receptor for advanced glycation end-products (RAGE) is a
      multiligand transmembrane receptor that is overexpressed in various pathological
      conditions including cancers. However, the expression pattern of RAGE in breast
      cancer tumors is still not completely clear. METHODS: In this study, we
      investigated the expression levels of RAGE in 25 fresh-frozen breast cancer
      samples and corresponding noncancerous tissue samples collected from breast
      cancer patients, by real-time polymerase chain reaction (PCR). Additionally, we
      performed immunohistochemistry on breast cancer specimens. RESULTS: The results
      indicate a high expression of the RAGE-encoding gene in the cancerous tissues.
      RAGE expression at the mRNA and protein levels was statistically significantly up
      regulated in advanced-stage and triple-negative breast tumors and node-positive
      tissues compared with other tissues (p < 0.001). A significant association
      between RAGE expression and tumor size was observed (p = 0.029). CONCLUSIONS:
      Overexpression of RAGE in advanced-stage tumors may be a useful biomarker for
      diagnosis and the prediction of breast cancer progression.

PMID- 27710975
TI  - A Multicenter Feasibility Study of EBUS-TBNA for Potentially Operable Non-Small
      Cell Lung Cancer: The JMTO LC07-02 Study (UMIN000001280).
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is a standard procedure for the pathological evaluation of the
      mediastinal nodal (N2) status of lung cancer; however, its feasibility in
      potentially operable patients with suspicion of minimal N2 disease remains
      unestablished. PATIENTS AND METHODS: A prospective multicenter study was
      conducted to assess the feasibility of EBUS-TBNA in this setting. Patients with
      clinical stage IIIA-N2 non-small cell lung cancer (NSCLC) and mediastinal nodal
      enlargement on computed tomography (CT) were eligible; patients were ineligible
      when CT revealed bulky (> 3 cm in the long-axis diameter) N2 or multiple (>= 3)
      station N2. If EBUS-TBNA revealed negative results, surgical staging procedures
      were mandatory. RESULTS: Among 20 eligible patients, EBUS-TBNA provided
      pathological confirmation of N2 disease (true-positive) in 12 patients. Among 8
      patients with negative results with EBUS-TBNA, 4 patients were pathologically
      diagnosed as having N2 disease with surgical staging procedures (false-negative),
      and 4 were finally diagnosed as having non-N2 disease with nodal dissection by
      thoracotomy (true-negative). As a result, the sensitivity of EBUS-TBNA for N2
      evaluation (primary endpoint) was 75.0% (95% confidence interval 47.6-92.7%). No
      grade 3-5 adverse event were documented. CONCLUSION: EBUS-TBNA is potentially
      safe and useful in the pathological evaluation of N2 status even in potentially
      operable NSCLC patients with suspicion of minimal N2 disease on preoperative CT.

PMID- 27710976
TI  - Consultation Program for Patients with Cancer-Related Fatigue: A Systematic
      Evaluation of the Experiences of the Bavarian Cancer Society.

PMID- 27710977
TI  - The Systemic Management of Advanced Melanoma in 2016.
AB  - Melanoma is a common type of skin cancer with a high propensity to metastasize.
      Tyrosine kinase inhibitors targeting the mitogen-activated protein kinase (MAPK)
      pathway and immune checkpoint blockade have recently revolutionized the
      management of unresectable and metastatic disease. However, acquired resistance
      and primary non-response to therapy require novel treatment strategies and
      combinations. The purpose of this review is to provide a brief and up-to-date
      overview on the clinical management and current trial landscape in melanoma. We
      summarize the most pertinent studies on BRAF/MEK inhibitors and blockade of
      cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death
      protein 1 (PD-1). Although most agents show robust antitumor efficacy as single
      agents, further improvements have been achieved by the combination of both
      approved and developing drugs. We discuss ongoing trials and evaluate future
      approaches that may provide additional efficacy with less toxicity.

PMID- 27710978
TI  - Efficacy and Long-Term Safety of Everolimus in Pancreatic Neuroendocrine Tumor
      Associated with Multiple Endocrine Neoplasia Type I: Case Report.
AB  - BACKGROUND: Approximately 10% of pancreatic neuroendocrine tumors (NET) are
      associated with familial syndromes, with the most common type being multiple
      endocrine neoplasia type 1 (MEN-1). However, the available evidence on how to
      treat NET comes from studies in sporadic NET. CASE REPORT: Here we report the
      case of a 51-year-old male patient with a metastatic MEN-1-associated pancreatic
      NET and hypercalcemia related to primary hyperparathyroidism and tumor-secreted
      parathyroid-related protein. The patient was treated with everolimus, and showed
      complete resolution of hypercalcemia and tumor control for 3 years when he
      presented with pulmonary cryptococcosis and disease progression. CONCLUSION: This
      case report describes the activity of everolimus in a patient with MEN-1
      associated pancreatic NET, its efficacy in treating malignant hypercalcemia
      associated with NET and the risk of opportunistic infections with prolonged use
      of this agent.

PMID- 27710979
TI  - Targeting Both Tumor and Stroma Cells to Treat Melanoma: NIPAWILMA.

PMID- 27710980
TI  - Surgical Strategy and Facial Nerve Outcomes in Petrous Bone Cholesteatoma.
AB  - OBJECTIVE: To review the classification and management of petrous bone
      cholesteatomas (PBCs) at our center and the outcomes of facial nerve (FN)
      management in these lesions. METHODS: This was a retrospective study. The setting
      was a quaternary referral center for skull base pathology in Italy. A total of
      200 patients with 201 PBCs were included in the study. All patients diagnosed
      radiologically with PBCs were classified according to the Sanna classification.
      All patients were surgically treated and followed up with radiology. The main
      outcome measures - classification of PBCs, the surgical approach used, disease
      control, and FN outcomes - were analyzed. RESULTS: Supralabyrinthine PBCs were
      the most common type with 92 cases (45.8%) followed by the massive PBCs with 72
      cases (35.8%). Preservation of preoperative FN function was highest in the
      infralabyrinthine (72.2%) and infralabyrinthine-apical (73.3%) types. The
      transotic approach was used in 66 cases (32.8%) in this series. The modified
      transcochlear approach type A was applied in 55 cases (27.3%). Active management
      of the nerve (rerouting, anastomosis, or grafting) was required in 53 cases
      (26.4%). Postoperatively, of the 116 cases with FN House-Brackmann grade I and
      II, 107 cases (92.2%) retained the same grade or improved. Recurrence was seen in
      7 cases (3.5%). The mean duration of follow-up was 6.3 years. CONCLUSIONS:
      Radical disease clearance must take precedence over hearing and FN preservation
      in PBCs. Active FN management, including rerouting, end-to-end anastomosis, and
      cable nerve grafting, routinely come to play in the surgical management of PBCs,
      and the postoperative FN results after such interventions can be satisfactory in
      most cases.

PMID- 27710982
TI  - Relationship between urinary incontinence symptoms and urodynamic findings using
      a validated Arabic questionnaire.
AB  - BACKGROUND: Urinary incontinence is common, particularly in women. Urodynamic
      studies (UDS) can accurately assess the condition. Less invasive objective
      measuring tools correlate with urodynamic findings, but the Arabic version of the
      Urogenital Distress Inventory-6 (UDI-6) questionnaire has not been previously
      correlated with UDS in Arabian patients. OBJECTIVE: To correlate the Arabic
      version of the UDI-6 with urodynamic findings in Arabian women with urinary
      incontinence. DESIGN: Prospective. SETTING: Tertiary referral urology clinic.
      PATIENTS AND METHODS: All female patients presenting with urinary incontinence
      between July 2013 to March 2014. Patients answered the Arabic UDI-6 questionnaire
      and underwent a history and clinical examination, urine culture and UDS. MAIN
      OUTCOME MEASURES: Correlation between Arabic UDI-6 questionnaire score and
      urodynamic diagnosis. RESULTS: Eighty-seven women with a mean age of 57 (range,
      22-72) years completed the UDI-6 and underwent UDS. The questionnaire revealed
      that 20 (23%) patients had urge incontinence, 28 (32%) had stress incontinence
      and 39 (45%) had mixed incontinence. As diagnosed by UDS, 26 (30%) had urge
      incontinence, 37 (42%) had stress incontinence, 16 (18%) had mixed incontinence
      and 8 (9%) had no abnormality. Eighty-six percent of patients (24/28) with pure
      stress urinary incontinence (SUI) symptoms had a positive UDS, and 55% (11/20) of
      patients with pure urge incontinence symptoms had a positive UDS. Of all patients
      with positiveresponse to the question for SUI, 53/67, 79% had positive UDS
      diagnosis with a correlation coefficient of 0.65 (P < .01). Of all patients with
      positive responses for urge incontinence, 27/59, 45.8% had positive UDS diagnosis
      with a moderate correlation coefficient of 0.38 (P < .01). CONCLUSIONS: The
      validated Arabic UDI-6 correlates significantly with UDS findings in Arabian
      women, particularly in women with SUI. LIMITATIONS: The sample size was
      relatively small, which prevented sub-analyses. Patient comorbidities were not
      evaluated.

PMID- 27710981
TI  - Clinical Practice Guidelines on the Screening and Treatment of Precancerous
      Lesions for Cervical Cancer Prevention in Saudi Arabia.
AB  - BACKGROUND: Cervical cancer is the third most common gynecological malignancy in
      Saudi women with an estimated incidence rate of 1.9 cases per 100 000 women
      years. More than 40% of cervical cancer cases are diagnosed at advanced stages
      due to lack of a routine screening program in Saudi Arabia. Thus, national
      guidelines for routine screening and treatment of precancerous cervical lesions
      are needed. METHODS: The Saudi Centre for Evidence-Based Healthcare invited a
      panel of local experts and partnered them with a team from McMaster University in
      Canada for methodological support, to develop national clinical practice
      guidelines on the screening and treatment of precancerous lesions for cervical
      cancer. After the panel identified key clinical questions, the McMaster
      University working group updated existing systematic reviews that had been used
      for the 2013 WHO Guidelines for screening and treatment of precancerous lesions
      for cervical cancer prevention. Recommendations were based on the GRADE (Grading
      of Recommendations, Assessment, Development and Evaluation) approach. Those
      recommendations took into account the available evidence, patient values and
      preferences, and resource use in the Saudi context. The panel provided
      recommendations on two major issues: screening for precancerous lesions (cervical
      intraepithelial neoplasia 2 & 3) and treatment of those lesions to prevent
      cervical cancer in women who tested positive after screening. CONCLUSIONS: The
      Saudi expert panel recommends using the HPV DNA test followed by colposcopy or
      cytology (Pap test) followed by colposcopy to screen for CIN2+ in women at risk
      of cervical cancer. The panel recommends cryotherapy or loop excision
      electrosurgery procedure (LEEP) over cold knife cone biopsy to treat women at
      risk of cervical cancer that tests positive for CIN2+. Universal screening for
      precancerous cervical dysplasia in women in Saudi Arabia is recommended using HPV
      testing and or cytology. Either cryotherapy or LEEP are preferred for treatment.
      LIMITATIONS: National studies on cervical cancer screening modalities and
      treatment of precancerous cervical lesions, including HPV prevalence and its
      association with cervical cancer, are scarce.

PMID- 27710983
TI  - Vitamin D content in fortified low fat milk in Saudi Arabia.
AB  - BACKGROUND: Vitamin D deficiency is common in many countries, including Saudi
      Arabia. Various population-level preventive measures have been implemented,
      including milk fortification with vitamin D. OBJECTIVES: The main objective of
      the study was to determine vitamin D levels in fortified low fat cow milk on the
      Saudi Arabian market and to compare it with the label claims. DESIGN: Cross
      sectional study. SETTING: Academic research center. MATERIALS AND METHODS: Five
      milk batches from five major producers were purchased in five replicates from
      five major retail stores in Riyadh, Saudi Arabia. We used a validated liquid
      chromatography assay to measure vitamin D levels. All samples were producer
      labeled to contain 400 IU/L (10 ng/mL) vitamin D and were analyzed within the
      first 40% of their validity period. Intra-batch, inter-batch, and inter-producer
      variations were determined as a coefficient of variation. MAIN OUTCOME MEASURES:
      Intra-batch, inter-batch and inter-producer variations in vitamin D level.
      RESULTS: Overall, mean (SD) measured vitamin D level was 10.2 (1.6) with a range
      of 7.1-13.9 ng/mL. In 25 of 125 samples (20%), the vitamin D level was outside +/
      20% of the label claim (10.4% under-fortified, 9.6% over fortified). Intra
      batch, inter-batch, and intra-producer variations were 1.6 -20.8%, 8.2-20.8%, and
      16.1%, respectively. CONCLUSIONS: Vitamin D content in fortified low fat cow milk
      on the Riyadh market matches label claim in 85% of the samples of major
      retailers. Variations from label claim in 15% of the samples are small and may
      not be clinically important. LIMITATIONS: This study was limited to five major
      retailers in the Riyadh area and did not examine full-fat or non-fat milk
      samples.

PMID- 27710984
TI  - The effect of parturient height on the median effective dose of intrathecally
      administered ropivacaine.
AB  - BACKGROUND: Pain during cesarean delivery is one of the more common reasons for a
      successful medicolegal claim. However, creating an extensive block area can
      result in hypotension, so determining the precise dose of local anesthetic is
      critical. OBJECTIVES: Investigate effects of parturient height on the median
      effective dose (ED50) of intrathecally-administered ropivacaine. DESIGN:
      Prospective cross-sectional analytic study. SETTING: Anesthesiology department in
      a provinicial hospital in China. METHODS: Parturients undergoing cesarean
      delivery under combined spinal and epidural anesthesia were stratified according
      to height as follows: 150 cm to 155 cm, 156 cm to 160 cm, 161 cm to 165 cm and
      166 cm to 170 cm. The spinal component of the anesthetic was established by bolus
      administration of up-and-down doses of 0.75% plain ropivacaine as determined by
      the Dixon method. The initial dose of ropivacaine was 5.79 mg and the testing
      interval dose change was set at 0.75 mg. The block height for the first cold
      feeling at T5 was considered satisfactory anesthesia. MAIN OUTCOME MEASURES: ED50
      values and vasopressor requirements, nausea, vomiting and shivering. RESULTS: In
      120 parturients, the ED50 for satisfactory block height using intrathecal
      ropivacaine was 5.92 mg (95% confidence interval[CI] 5.02-6.86 mg) patients of
      150 to 155 cm in height; 6.52 mg (95% CI 5.45-7.65 mg) in 156 cm to 160 cm; 7.49
      mg (95%CI 6.83-8.25 mg) in 161 cm to 165 cm; 8.35 mg (95%CI 7.55-9.23 mg) in 166
      to 170 cm. The ED50 of ropivacaine increased with increasing height of the
      subject. There were no significant differences in incidence of hypotension,
      vasopressor requirements, nausea, vomiting and shivering. CONCLUSION: The ED50 of
      intrathecal ropivacaine using sensitivity to cold sensation increased with
      parturient height, indicating that dose may be determined in part by height.
      LIMITATION: The ED95 rather than the ED50 for spinal anesthesia is more useful
      clinically. We did not control for the effect of weight on the dose of local
      anesthetic. Factors such as baricity, volume, concentration injected, temperature
      of the solution, and viscosity can affect intrathecal spread of the local
      anesthetics and block quality.

PMID- 27710985
TI  - Fasting plasma glucose levels and coronary artery calcification in subjects with
      impaired fasting glucose.
AB  - BACKGROUND: Prediabetes is associated with an increased risk of cardiovascular
      disease (CVD). While the association of impaired glucose tolerance with CVD has
      been shown in many studies, the relationship between impaired fasting glucose
      (IFG) and CVD remains unclear. OBJECTIVES: The purpose of this study was to
      compare the coronary artery calcium (CAC) scores of participants with normal
      fasting glucose versus those with IFG, according to fasting plasma glucose (FPG)
      levels, and to assess whether differences in CAC scores were independent of
      important confounders. DESIGN: Retrospective study. SETTING: Health Promotion
      Center of the University Hospital (Gyeonggi-do, South Korea), during the period
      2010-2014. PATIENTS AND METHODS: Participants were enrolled from the general
      population who visited for a medical check-up. CAC was assessed in asymptomatic
      individuals by multidetector computed tomography. Anthropometric parameters and
      metabolic profiles were also recorded. Subjects were divided into four fasting
      glucose groups. Participants with a history of CVD or diabetes mellitus were
      excluded. MAIN OUTCOME MEASURES: Correlation between FPG and CAC scores, CAC
      score categories, and association between CAC score and FPG categories. RESULTS:
      Of 1112 participants, 346 (34.2%) had a CAC score > 0. FPG values in the IFG
      patients were positively but weakly correlated with CAC scores (r=0.099, P=.001).
      The incidence of CAC differed according to FPG level (P < .001) and in Kruskal
      Wallis test the mean CAC score differed by FPG group (P < .001). After adjustment
      for other factors in a multiple logistic regression analysis, those subjects with
      FPG >=110 mg/dL had a significantly higher risk of CAC than did subjects with
      normal fasting glucose (110.

PMID- 27710987
TI  - Prevalence and factors associated with geriatric malnutrition in an outpatient
      clinic of a teaching hospital in Jeddah, Saudi Arabia.
AB  - BACKGROUND: Malnutrition is highly prevalent among the elderly and is associated
      with poor clinical prognosis, decreased functional status, and increased
      morbidity and mortality. OBJECTIVE: To estimate the prevalence of geriatric
      malnutrition among outpatients of a geriatric clinic and to determine factors
      associated with malnutrition. DESIGN: Cross-sectional study. SETTING: Geriatric
      outpatient clinic of the King Abdul Aziz University Hospital, Jeddah. PATIENTS
      AND METHODS: All patients older than 60 years of age who attended the clinic
      during January 2016 were eligible for inclusion. Nutritional status was assessed
      using anthropometric data and by hemoglobin and albumin levels and lymphocyte
      count. The MNA was used to define malnutrition. MAIN OUTCOME MEASURES:
      Anthropometric measures, biochemical tests, and the scores on the short version
      of the Mini Nutritional Assessment (MNA). RESULTS: According to the MNA results,
      8 (5.3%) of 152 elderly patients suffered overt malnutrition and 50 (32.9%) were
      at risk of malnutrition (71 males and 41 females; aged 72.4 [8.6] years). The
      prevalence of malnutrition was significantly higher among females (44.6%; 95% CI,
      1.01-4.08; P=.044) than in males (28.3%). Malnourished patients were older than
      patients with normal nutritional status (mean 72.4 [8.6] years), and more common
      in patients who lived alone (62.5%). The malnourished patients had significantly
      smaller calf circumferences (63.4; 95% CI, 1.51-3.20; P=.001), and lower albumin
      and hemoglobin levels (P=.001). A significantly higher percentage of the
      malnourished patients compared with normal patients had experienced weight loss
      (37.9%; P < .001) and decreased food intake (56.9%; P < .001) during the previous
      three months. Binary logistic regression revealed that being female and living
      alone were significant predictors for being categorized as malnourished or at
      risk of malnutrition. CONCLUSION: The prevalence of malnutrition is high among
      geriatric outpatients. Routine screening for malnutrition among geriatric
      patients would allow early diagnosis and prompt intervention. LIMITATIONS: The
      heterogeneity of the study group (different diseases at different stages) could
      influence the generalizability of our findings. The relatively small number of
      patients (P=.002) is a potential limitation.

PMID- 27710986
TI  - The epidemiology of pituitary adenomas in a community-based hospital: a
      retrospective single center study in Saudi Arabia.
AB  - BACKGROUND: Data on pituitary adenoma (PA) prevalence in Saudi Arabia are scarce.
      OBJECTIVE: To estimate the epidemiology of PA in a well-defined population.
      DESIGN: Retrospective analysis. SETTING: Departments of Endocrinology and
      Radiology at King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia. PATIENTS AND
      METHODS: Radiological and hormonal data of patients with pituitary adenoma by MRI
      were reviewed for the period January 2008 to December 2015. MAIN OUTCOME
      MEASURES: Prevalence of PA and hormonal abnormalities. RESULTS: Of 537 patients;
      249 subjects (46.4%), 70 (28.1%) males and 179 (71.9%) females, were diagnosed to
      have PA with mean age 36.3 (14.1) years. Microadenoma and macroadenoma were seen
      in 171 (69%) and 78 (31%) subjects, respectively. Microadenomas were more
      prevalent than macroadenomas (68.7% vs. 31.3%). Microadenomas were significantly
      more prevalent in females, 131 (73.2 %) vs. 40 (57.1%) whereas macroadenomas were
      significantly more prevalent in males, 30 (42.9%) vs. 48 (26.8%) (P < .001 for
      both comparisons). Patients with microadenomas were significantly younger than
      patients with macroadenomas (P < .0001). Advanced age was significantly
      associated with a larger PA size (r=0.39, P < .0002). Three types of
      hyperfunctioning PA were seen: prolactinoma, somatotroph adenoma, and
      corticotroph adenoma. Five types of hypofunctioning PA were seen:
      panhypopituitarism, secondary hypogonadism, growth hormone deficiency, central
      hypothroidism and central adrenal insufficiency. Non-functioning PA were within
      normal laboratory hormonal values in 2% of cases. CONCLUSION: Our study showed
      that the prevalence of PA was greater than previously reported. This increased
      prevalence may have important implications when prioritizing funding for research
      and treatment of PA. LIMITATIONS: Clustering of cases within the study region
      might have affected estimates and limited study sample size.

PMID- 27710988
TI  - Outcome of loop versus divided colostomy in the management of anorectal
      malformations.
AB  - BACKGROUND: Colostomy is a common part of the management of high anorectal
      malformation (ARM) in the pediatric population. OBJECTIVE: To evaluate whether
      the type of colostomy (loop vs divided) has an impact on outcome in patients with
      ARM. DESIGN: A retrospective study. SETTING: King Faisal Specialist Hospital and
      Research Center, a tertiary care center. PATIENTS AND METHODS: All patients who
      were managed with colostomy for ARM and had definitive repair during the period
      of January 2000 to December 2014. Outcomes relative to the type of the colostomy
      were compared. MAIN OUTCOME MEASURES: Morbidities associated with each type of
      colostomy. RESULTS: There were 104 patients managed for ARM with colostomy as
      staged procedures, 63 males and 41 females. Patients had a colostomy at a median
      age of 6 days and were closed at a median of 11 months. Definitive repair was at
      a median age of 17 months. Type of fistula was 8 perineal, 21 rectovestibular, 35
      rectourethral, 11 rectovesical and there were 16 without fistula and 13 cloaca
      anomalies. There were 55 loop and 49 divided colostomies. There were 91
      descending/sigmoid and 13 transverse colostomies. Operative time for loop
      colostomy closure was shorter than with divided colo6stomy (76 minutes vs 94
      minutes, P=.002). Three patients among the divided group had reversed orientation
      of the colostomy that had affected bowel preparations negatively prior to its
      repair. There was no differences in complications of creation and closure of loop
      and divided colostomies except in occurrence of skin excoriation. There was more
      skin excoriation with divided colostomy compared to loop colostomy (17 vs 10,
      P=.04). CONCLUSIONS: Loop colostomy has a shorter closure operative time and
      relatively fewer complications compared to the divided colostomy. Our data
      suggests that loop colostomy may be more favorable than divided colostomy for ARM
      patients. LIMITATIONS: Retrospective nature of the study and some colostomies
      performed at other hospitals.

PMID- 27710989
TI  - The impact of renal angiomyolipoma on estimated glomerular filtration rate in
      patients with tuberous sclerosis complex.
AB  - BACKGROUND: There is a growing concern that renal impairment may develop in
      patients with renal angiomyolipomas (AMLs) associated with tuberous sclerosis
      complex (TSC) as a consequence of the disease itself and/or the interventions to
      mitigate the risk of hemorrhage. OBJECTIVE: To assess the estimated glomerular
      filtration rate (eGFR) in patients with bilateral renal AMLs and the impact of
      tumor burden and intervention on renal function. DESIGN: Retrospective study.
      SETTING: Urology department of a tertiary care hospital. PATIENTS AND METHODS:
      All adult patients (>=18 years of age) with TSC-associated renal AMLs seen from
      October 1998 to June 2015. We included only patients with bilateral tumors or
      solitary kidneys at the last follow-up. MAIN OUTCOME MEASURES: The eGFR, renal
      volume, and number and type of interventions. RESULTS: We identified 12 patients
      (median age 27.6, interquartile range 23.7-39.9 years), a median follow-up period
      of 1266 days (33-3133), and a median renal size of 454.7 mL (interquartile range
      344.7-1016.9 on the right side; 558.1 mL, interquartile range 253.7-1001.4 on the
      left). In 11 (91.7%) patients, the eGFR was > 60 mL/min/1.77 m2. Six patients had
      three total nephrectomies, one had a contralateral partial nephrectomy, and seven
      had selective arterial embolizations. Intervention was associated with a
      significantly reduced eGFR. The renal size did not correlate with the eGFR.
      CONCLUSIONS: TSC-associated renal AMLs may attain a large size but normal renal
      function is maintained in 92% of patients. Interventions to mitigate the risk of
      hemorrhage are associated with decreased renal function. LIMITATIONS: The renal
      size was used as a surrogate for tumor size. Other limitations were the limited
      number of patients and lack of split renal function testing.

PMID- 27710991
TI  - Identification of gout in unusual sites by dual energy computed tomography.

PMID- 27710990
TI  - Coexistence of chronic lymphocytic leukemia and polycythemia vera: a case report
      and review of the literature.
AB  - : Polycythemia vera is a Philadelphia chromosome-negative myeloproliferative
      neoplasm. Chronic lymphocytic leukemia is a monoclonal expansion of a CD5+ CD19+
      B lymphocytes. Chronic myeloproliferative neoplasms may coexist with indolent B
      cell malignant lymphomas of various types. The association of chronic lymphocytic
      leukemia with polycythemia vera is a rare event with only a few cases of
      coexistence ever reported. We report a 56-year-old man in whom these two
      disorders were diagnosed concomitantly. Possible etiopathogenic relationships
      between both disorders are discussed in this case report. SIMILAR CASES
      PUBLISHED: 6.

PMID- 27710992
TI  - Dynamics of Feeding for Infants, Young Children, and Families.

PMID- 27710993
TI  - Interdisciplinary Feeding Team: A Medical, Motor, Behavioral Approach to Complex
      Pediatric Feeding Problems.
AB  - Pediatric feeding difficulties are complex and multifactorial in nature. Children
      who need assessment and individualized treatment for complex feeding problems are
      best served by an interdisciplinary treatment team. The medical, motor, and
      behavioral approach to treating pediatric feeding problems is presented as an
      avenue to treatment. By necessity, this approach requires a well-functioning
      interdisciplinary team, including nurses, physicians, registered dietitians, and
      feeding therapists (speech-language pathologists, occupational and physical
      therapists). We describe a robust interdisciplinary feeding team that applies a
      medical, motor, and behavioral approach to treating pediatric feeding problems.
      Within this team, pediatric gastroenterology nurse practitioners, dietitians, and
      speech pathologists function as integral members of the team. Description of each
      team member's expertise is provided and how they operate to support children with
      feeding problems and their families.

PMID- 27710995
TI  - Infant Deaths From Use of Crib Bumpers Are Increasing.

PMID- 27710994
TI  - Development of Feeding Cues During Infancy and Toddlerhood.
AB  - PURPOSE: To enhance responsive feeding, this study aimed to characterize the
      development of feeding cues during infancy and toddlerhood. STUDY DESIGN AND
      METHODS: A secondary analysis was performed on a dataset of first-time, low
      income African American mother-infant pairs assessed at infant age 3, 6, 9, 12,
      and 18 months. A subsample with the 15 highest, middle, and lowest infant body
      mass index (BMI) Z-scores at 18 months was selected (n = 45). Using video
      recorded home feedings, early, active, and late receptiveness and fullness cues
      were assessed using the Responsiveness to Child Feeding Cues Scale at each time
      point. Descriptive statistics were used to characterize development. RESULTS:
      Early receptiveness cues were relatively rare over time, whereas active
      receptiveness cues were much more common. However, there were changes over time.
      For example, settling into the feeding decreased from ~50% at 3 and 6 months to
      4.8% by 18 months, whereas postural attention and reaching for food increased
      after 6 months. In the first 6 months, falling asleep and decreasing muscle tone
      and activity level were the most common early fullness cues. Thereafter, taking
      interest in surroundings was most prevalent. Active fullness cues became
      increasingly diverse after 6 months, led by more assertive cues such as pushing
      or pulling away and communicating "no" verbally or nonverbally. CLINICAL
      IMPLICATIONS: These findings provide an empirical description of waxing and
      waning in feeding cues and indicate increasing intentionality of cues over the
      first 18 months of life. Knowing common cues across development may aid
      clinicians in enhancing parental feeding responsiveness, avoiding overfeeding,
      thereby decreasing risk of early childhood obesity.

PMID- 27710996
TI  - What Is Your mPINC Score?

PMID- 27710997
TI  - By Small and Simple Things: Clean Birth Kits.

PMID- 27710999
TI  - Missed Nursing Care in the Perinatal Setting.

PMID- 27711000
TI  - Implementing Co-Regulated Feeding with Mothers of Preterm Infants.

PMID- 27711001
TI  - Milk flow rates from bottle nipples used after hospital discharge.

PMID- 27711002
TI  - CROWN Endorses a Core Outcome Set for Studies on Preterm Birth Prevention.

PMID- 27711003
TI  - UNUSUAL POSTERIOR VARIX OF A VORTEX VEIN AMPULLA.
AB  - PURPOSE: We describe a patient with an unusually posterior varix of a vortex vein
      ampulla. METHODS: Case report. RESULTS: An unusually posterior varix of a vortex
      vein ampulla mimicking a choroidal neoplasm was identified. The diagnosis was
      obscured by the presence of overlying drusen. Through a combination of
      indocyanine green angiography and enhanced depth imaging optical coherence
      tomography, the varix was identified as an engorged vascular process correlating
      to ophthalmoscopic and tomographic examination. Collapse of the varix after
      direct digital pressure on the globe was observed on enhanced depth imaging
      optical coherence tomography further confirming our diagnosis. CONCLUSION:
      Varices of vortex vein ampullas may be incorrectly diagnosed as choroidal
      neoplasms. Using a combination of multimodal imaging and dynamic maneuvering,
      varices can be correctly identified.

PMID- 27711004
TI  - UNUSUAL CASE OF STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS.
AB  - PURPOSE: To report a case of unilateral stellate nonhereditary idiopathic
      foveomacular retinoschisis (SNIFR) in a young male showing structural changes
      induced by a Valsalva maneuver. METHODS: Case report of a 26-year-old oboist with
      SNIFR, including multimodal imaging. Eye-tracked spectral-domain optical
      coherence tomography (SD-OCT) was used to compare the retinal architecture at
      rest and during a Valsalva maneuver. RESULTS: Spectral-domain optical coherence
      tomography showed macular and peripapillary retinoschisis with no signs of
      pathologic myopia, optic pit, or vitreoretinal traction. A full-field
      electroretinogram showed supranormal responses in the eye studied. Magnetic
      resonance imaging of the brain showed no abnormalities. Eye-tracked SD-OCT scans
      showed an increase in retinal thickness reaching 28 microns superior to the disc
      during an induced Valsalva maneuver. CONCLUSION: Stellate nonhereditary
      idiopathic foveomacular retinoschisis is a diagnosis made when other known causes
      of retinoschisis have been excluded. In this patient with unilateral SNIFR, an
      increase in retinal thickness during a Valsalva maneuver was demonstrated.
      Further study would be needed to determine the mechanism producing this change
      and to assess its potential influence on visual prognosis.

PMID- 27711006
TI  - Liver transplantation 2007: where do we go from here?

PMID- 27711007
TI  - Current status of liver transplantation for hilar cholangiocarcinoma.
AB  - PURPOSE OF REVIEW: Liver transplantation for unresectable hilar
      cholangiocarcinoma is a highly controversial issue. This review will summarize
      results with transplantation alone and a new strategy of high-dose neoadjuvant
      chemoradiotherapy and subsequent liver transplantation. The review will address
      controversies regarding this novel approach to the treatment of hilar
      cholangiocarcinoma, including prioritization of patients with cholangiocarcinoma
      awaiting scarce deceased donor livers. RECENT FINDINGS: Results with liver
      transplantation alone for patients with unresectable cholangiocarcinoma are poor
      and do not justify use of scarce donor livers for these patients. Several centers
      have recently reported excellent results combining high-dose neoadjuvant
      chemoradiotherapy and liver transplantation for patients with early stage
      disease. Patient selection, operative staging, timely transplantation, and strict
      adherence to protocol are keys to success. SUMMARY: Hilar cholangiocarcinoma -
      once a contraindication for transplantation - has reemerged as an indication for
      transplantation when combined with neoadjuvant therapy. Results are comparable to
      results achieved with liver transplantation for other indications and exceed
      results with standard resection.

PMID- 27711008
TI  - Donation after cardiac death and liver transplantation.
AB  - PURPOSE OF REVIEW: This review discusses recent results and analyses on the use
      of donation after cardiac death (DCD) allografts in liver transplantation,
      including outcomes based on donor and recipient risk stratification, as well as
      associated postoperative complication rates. RECENT FINDINGS: Outcomes from the
      use of DCD donors can be improved with selective and appropriate donor-recipient
      pairings, although the optimum combination remains undetermined. Older DCD donors
      can be utilized, and arguments are presented for withdrawal of life support
      processes in the intensive care unit rather than in the operating room. SUMMARY:
      Increasing the donor pool for liver transplantation is required to prevent many
      of the deaths that occur while the patient is on the wait list. Under specific
      conditions, many studies report positive outcomes from of the use of DCD donors
      for liver transplantation.

PMID- 27711009
TI  - Machine perfusion preservation of the liver: a worthwhile clinical activity?
AB  - PURPOSE OF REVIEW: Although successful machine perfusion procedures of the liver
      were first performed almost four decades ago, technical and logistical
      constraints have prevented general acceptance. Interest in the procedure has
      recently been renewed due to its potential to resuscitate marginal organs. This
      review describes experimental and clinical liver hypothermic machine perfusion
      studies and current developments. RECENT FINDINGS: Experimental studies have
      shown that oxygenated hypothermic machine perfusion provides a complete washout
      and can restore parenchymal energy status, a phenomenon of particular importance
      in preservation of livers from compromised donors. Additionally, perfusion of the
      hepatic artery can prevent ischemic-type biliary lesions. Short-term and
      continuous hypothermic machine perfusion prior to or after cold storage
      preservation have proven more effective than cold storage alone. SUMMARY: The
      benefits of hypothermic machine perfusion for both heart-beating and nonheart
      beating liver grafts seem promising in terms of expanding the donor pool. As
      liver hypothermic machine perfusion systems are not yet commercially available,
      the process is currently only clinically used for kidney grafts. Clinical
      application appears feasible in the near future as new, easy-to-use systems and
      solutions are currently under development.

PMID- 27711010
TI  - Transmission of viral disease to the recipient through the donor liver.
AB  - PURPOSE OF REVIEW: Morbidity and mortality after liver transplantation continue
      to be significantly influenced by infectious complications. A particular concern
      is transmission of pathogens through the graft, which may cause significant
      disease in the recipient. RECENT FINDINGS: For frequently transmitted herpes
      viruses with high seroprevalence such as cytomegalovirus, Epstein-Barr virus and
      human herpes viruses 6 and 7, significance, diagnosis, spectrum of disease in the
      recipient, prophylaxis and therapy are well established. Less is known about rare
      viruses such as West Nile virus, rabies virus, human choriomeningitis virus,
      human herpes virus 8 and human T-cell lymphoma 1, which are in many cases fatal.
      A plenitude of other viruses that potentially can be transmitted with a donor
      liver may exist, for which no detailed information is currently available. Grafts
      from anti-hepatitis B virus core antibody positive donors can be safely used when
      using lamivudine/hepatitis B immunoglobulin prophylaxis; hepatitis C virus
      positive organs should be given to hepatitis C virus positive individuals only.
      SUMMARY: With the utilization of increasingly extended criteria donors, the risk
      for transmission of viruses with the graft may become a more common complication.
      These viruses will include rare and new pathogens and testing donors for these
      viruses may become necessary.

PMID- 27711011
TI  - The role of antibody induction in liver transplantation.
AB  - PURPOSE: Antilymphocyte antibody induction has been used in liver transplantation
      for decades, initially as part of a triple or quadruple immunosuppressive
      protocol to prevent rejection or in the treatment of steroid-resistant rejection.
      More recently there has been renewed interest in antibody induction in liver
      transplantation as part of a strategy to eliminate or reduce one or more
      immunosuppressive agents. This review highlights recent advances in the role of
      antibody induction in liver transplantation. RECENT FINDINGS: Primary interest in
      antibody induction now falls into four major categories: steroid avoidance;
      calcineurin inhibitor reduction as a renal sparing protocol; minimal
      immunosuppression protocols (tolerance); and limiting hepatitis C recurrence.
      These protocols usually involve short courses of antibody induction in the
      peritransplant period, with decreased reliance on other agents after
      transplantation. Recent reports demonstrate several beneficial effects of
      antibody induction and suggest that, in the Model for End-Stage Liver Disease
      era, antibody induction in immunosuppressive strategies in liver transplantation
      will become increasingly important. SUMMARY: Antibody induction in liver
      transplantation confers valuable benefit in limiting the adverse effects of
      maintenance immunosuppression. Antibodies allow the subsequent reduction or
      elimination of other agents to minimize overall immunosuppression.

PMID- 27711013
TI  - Intestinal transplantation: an underused transplant procedure.

PMID- 27711012
TI  - Liver-kidney transplantation in the Model for Endstage Liver Disease era: is it
      overdone?
AB  - PURPOSE OF REVIEW: Simultaneous liver-kidney transplantation is increasing. This
      stimulates concern about unnecessary kidney transplantation (for acute kidney
      failure, hepatorenal syndrome) in liver transplant candidates. RECENT FINDINGS:
      Liver transplants are allocated by the Model for Endstage Liver Disease (MELD)
      score - a number heavily weighted by the serum creatinine. The serum creatinine
      value varies depending upon the laboratory where it is measured, is different
      between genders without a correction factor in MELD and is generally inaccurate
      as a marker of kidney function in liver failure. Criteria for dual
      transplantation vary between programs and there is no official oversight of the
      practice. Up to 6.5% of simultaneous transplant candidates on dialysis at listing
      discontinue dialysis before transplant. Furthermore, simultaneous liver-kidney
      transplant compared with liver transplant alone improves survival only for those
      liver candidates on dialysis at transplant. SUMMARY: It is time to review the
      allocation of kidney allografts to liver transplant candidates to avoid
      inappropriate transplantation. More complete investigation of kidney function
      following simultaneous liver-kidney transplantation is needed, in addition to
      improved methods to determine the recoverability of renal dysfunction in liver
      transplant candidates. Before an optimal algorithm is possible, however, basic
      and clinical investigation will be needed.

PMID- 27711014
TI  - Home parenteral nutrition in adults.
AB  - PURPOSE OF REVIEW: This review summarizes the latest epidemiologic data, and
      indications and methods for preventing complications from home parenteral
      nutrition (HPN), and it discusss survival, prognosis and quality of life of HPN
      patients who are potential candidates for intestinal transplantation. RECENT
      FINDINGS: Although alteration in hepatic enzymes is frequent with HPN, severe HPN
      related liver disorders are rare because of improvements in nutritional support.
      In experienced centres, likelihood of survival in HPN patients may reach 86% and
      71% at 1 and 10 years, respectively. About 15% of adult HPN patients are
      potential candidates for intestinal transplantation. SUMMARY: Complications
      include catheter-related sepsis and thrombosis, metabolic disorders, nutritional
      deficiency, psychological alteration and rehabilitation problems. Recent studies
      found that catheters lasted for 1.5 years on average. Alteration in hepatic
      enzymes alterations is frequent but severe liver complications are rare. Bone
      alterations occur in 75% of HPN patients, with multifactorial aetiology. Lipid
      administration should not exceed 1 g/kg per day. Overall probability of survival
      is good at 1 and 10 years; 10% of deaths are due to HPN complications. A large
      survey in European centres revealed that 15% of adults and 34% of children are
      candidates for intestinal transplantation.

PMID- 27711015
TI  - Is there a role for 'acute' or 'preemptive' intestinal transplantation?
AB  - PURPOSE OF REVIEW: 'Preemptive' transplantation is performed before underlying
      disease becomes advanced, compromising transplant feasibilities and
      posttransplant outcome while 'acute' transplant is performed when organ function
      is compromised and there is life-threatening risk. In intestinal transplantation
      an indication for transplant is failure of total parenteral nutrition in patients
      with intestinal insufficiency: liver disease associated with intestinal failure
      has a primary role in choosing the type of transplant to be performed and in
      establishing timing of transplantation. RECENT FINDINGS: Development of hepatic
      dysfunction represents an indication for preemptive intestinal transplantation at
      less than 1 year of parenteral nutrition. Regression of intestinal-failure liver
      disease may be achieved by isolated intestinal transplantation without liver
      grafting when liver disease is reversible. Therefore an early or preemptive
      indication for intestinal transplantation, in selected cases, represents liver
      salvage therapy associated with increased survival. Indications for acute
      intestinal or multivisceral transplant are few and confined to emergency trauma
      involving liver/bowel integrity and function, but above all the need of
      retransplant for multivisceral transplant recipients. SUMMARY: A preemptive
      isolated intestinal transplantation is strongly advised when liver disease occurs
      (if reversible) while there are only few clinical indications for acute
      intestinal transplantation (unless a multivisceral retransplant is needed).

PMID- 27711016
TI  - Intestinal transplantation: current improvements and perspectives.
AB  - PURPOSE OF REVIEW: This review summarizes the most recent relevant knowledge in
      clinical practice in the field of intestinal transplantation. RECENT FINDINGS:
      Three important factors that have allowed improving results during the last few
      years are reviewed here. The first relates to the development of a different
      approach to tackle the underlying cause of intestinal failure and to the
      patient's characteristics in terms of liver function, age, and body size. The
      second involves immune modulation and especially the immunosuppressive regimen at
      induction. The third refers to posttransplantation monitoring, in particular the
      diagnosis and treatment of intestinal graft rejection and lymphoproliferative
      disorders. Patient status and referral for intestinal transplantation remain
      debated. The Intestinal Transplant Registry and a report from an individual
      program have demonstrated the relationship between a patient's pretransplant
      status and outcome. Candidacy for intestinal transplantation was analysed in a
      European survey of home parenteral nutrition patients. Early referral and listing
      are important for successful outcomes after intestinal grafting. SUMMARY: Patient
      management should include therapies adapted to each stage of intestinal failure
      based on a multidisciplinary approach in centers involving surgery,
      gastroenterology, parenteral nutrition expertise, home parenteral nutrition
      programs, and liver-intestinal transplantation experience. Timing for referral of
      patients in specialized centers remains a crucial issue.

PMID- 27711017
TI  - Advances in anesthesia and organ transplantation: pearls of wisdom from the
      pioneers.

PMID- 27711018
TI  - Liver transplantation and pulmonary hypertension: pathophysiology and management
      strategies.
AB  - PURPOSE OF REVIEW: Increases in pulmonary artery pressure are seen in 20% of
      patients with liver cirrhosis due to a high cardiac output state together with
      circulatory volume overload. Some patients develop true pulmonary arterial
      hypertension with pathological changes in the pulmonary vasculature, an elevated
      pulmonary vascular resistance, and an increased transpulmonary gradient. Survival
      of patients with portopulmonary hypertension is poor once it becomes moderate to
      severe, whether or not liver transplant is undertaken. This increase in mortality
      is the result of right heart dysfunction. RECENT FINDINGS: Screening for
      portopulmonary hypertension occurs in most transplant centers using Doppler
      echocardiography to determine the right ventricular systolic pressure. The role
      of right heart function has been identified as a significant component in the
      survival of the new graft and the recipient during orthotopic liver transplant.
      SUMMARY: Our understanding of the management of patients with portopulmonary
      hypertension and the role of liver transplantation is improving as the results of
      multicenter databases are analyzed. Single center series are reaching a
      reasonable size, adding to our knowledge base, and helping in the development of
      evidence-based practice guidelines. The importance of right heart function and
      the use of perioperative echocardiography are better defined in the management of
      orthotopic liver transplant.

PMID- 27711019
TI  - Fluid therapy in organ transplantation.
AB  - PURPOSE OF REVIEW: Fluid management remains a controversial subject in
      perioperative medicine and organ transplantation. Various case series, anecdotes
      and tradition guide many fluid choices, especially when good evidence is lacking.
      Recent advances in the understanding of pharmacokinetic and pharmodynamic
      profiles of fluids, as well as transplantation physiology and pathophysiology,
      can guide us in new approaches to common problems. RECENT FINDINGS: This review
      is intended to describe some of the latest thinking on subjects like saline
      induced hyperchloraemic metabolic acidosis, the use of goal-directed approaches
      to volume resuscitation in perioperative medicine, the relative lack of evidence
      for low central venous pressure techniques in liver transplantation, some of the
      drug effects of intravenous fluids, as well as the complex issue of different
      crystalloids and colloids in renal transplantation. SUMMARY: Fluid therapy in
      transplant medicine is usually best practiced using goal-directed approaches and
      balanced electrolyte formulations when possible, even in renal failure. Some
      fluids may exert drug effects that could alter organ preservation and
      reperfusion, while the certain hydroxyethyl starches appear to be less toxic in
      renal transplantation than first suspected, especially when clinicians consider
      free water requirements in these settings.

PMID- 27711020
TI  - Liver transplantation and risk of bleeding.
AB  - PURPOSE OF REVIEW: Blood loss in orthotopic liver transplantation has declined
      during the past decade. Recent papers addressed this issue and emphasized its
      importance, because there is a significant correlation between intraoperative
      blood transfusion requirements and postoperative morbidity. This review addresses
      changes in practice that might have led to reduced blood loss. RECENT FINDINGS:
      Many preoperative variables that predict blood loss during orthotopic liver
      transplantation have been found. These vary between studies. Differences in
      perioperative blood loss, transfusion criteria and intraoperative management of
      coagulation may account for the interhospital variations in transfusion of red
      blood cells during orthotopic liver transplantation. Therefore, a risk index
      developed in one centre should not be applied without evaluation in other
      centres. Introduction of the piggyback technique and close monitoring of
      coagulation with thromboelastography have led to reduced blood transfusion
      requirements. Use of antifibrinolytics has shown to decrease blood loss.
      Recombinant factor VIIa is not indicated for treatment of coagulation
      abnormalities during orthotopic liver transplantation, and its use is justified
      only as rescue therapy. SUMMARY: Recent changes in blood conservation practices
      in orthotopic liver transplantation are presented and discussed.

PMID- 27711021
TI  - Impact of the Model for Endstage Liver Disease score on liver transplantation.
AB  - PURPOSE OF REVIEW: Allocation of deceased donor livers for transplantation is
      currently based on the Model for Endstage Liver Disease (MELD) score, which has
      fundamentally changed liver transplantation since its implementation in 2002.
      This review discusses the development, impact and problems associated with the
      system. RECENT FINDINGS: The MELD system was developed to provide a more
      objective means of prioritizing candidates for liver transplantation and to
      allocate livers based on greatest medical need. Liver allocation based on MELD
      score has had a remarkable effect, such as reducing waiting list mortality and
      increasing transplantation among patients with greater severity of illness,
      without a measurable decrement in postoperative survival. Unfortunately,
      potential problems have been identified. These include wide variation in illness
      severity in recipients; significant variation in MELD score depending on the
      clinical laboratory utilized to measure international normalized ratio; and a
      three-fold increase in the number of liver-kidney transplant recipients. SUMMARY:
      While MELD-based liver allocation has resulted in a marked improvement in liver
      allocation, there are still problems with the system. The challenge for the liver
      transplantation community is to prospectively evaluate the liver allocation
      system to ensure it remains the most effective and fair means of allocating
      deceased donor livers.

PMID- 27711022
TI  - Donation after cardiac death.
AB  - PURPOSE OF REVIEW: The present review will provide anesthesiologists with the
      scientific information and ethical arguments they need to make decisions about
      donation after cardiac death (DCD) for their clinical practices. RECENT FINDINGS:
      Organs derived from DCD benefit patients who would otherwise die without
      transplantation. The practice of DCD ties the withdrawal of life support to organ
      donation. The close approximation of cessation of circulation to the recovery of
      organs demands a systematically structured approach to ensure that patient care
      at the end of life will not be sacrificed for organ donation. In response, the
      medical community has developed standards of care through expert opinion and
      consensus. There is general agreement that patients are entitled to expert care
      at the end of life whether or not they will be organ donors. Thus, abrupt
      transfer of patient care to an anesthesiologist is usually not in the best
      interest of the patient. SUMMARY: By 2007, all US hospitals will have protocols
      for DCD. Anesthesiologists should review existing protocols and participate in
      the development of new ones to ensure that the approach to DCD conforms to
      current standards and that patients have a designated care provider for the
      withdrawal of life support.

PMID- 27711023
TI  - Current World Literature.

PMID- 27711024
TI  - Reference Intervals of Thromboelastometric Evaluation of Coagulation in Pediatric
      Patients with Congenital Heart Diseases: A Retrospective Investigation.
AB  - BACKGROUND Rotational thromboelastometry (ROTEM(r)) is a point-of-care test for
      coagulation, enabling physicians to make a swift decision. The aim of this
      investigation was to establish reference intervals of thromboelastometric
      evaluation for coagulation in pediatric patients with congenital heart diseases
      (CHD). MATERIAL AND METHODS As baseline data, 3 assays of ROTEM(r) (INTEM, EXTEM,
      and FIBTEM) were measured after anesthesia induction. ROTEM(r) parameters were
      clotting time (CT), amplitude at 10 min (A10), clot formation time (CFT), a
      angle, maximal clot firmness (MCF), clot lysis index at 60 min (LI60), and
      maximal clot elasticity (MCE). As age is a well-known factor for maturation, age
      groups were determined as follows; 1) <1 month, 2) 1-3 months, 3) 4-12 months, 4)
      1-3 years, 5) 4-6 years, 6) 7-12 years, and 7) 13-16 years. Reference limits
      representing 95% of distribution of ROTEM(r) parameters and 90% confidence
      intervals of upper and lower reference limits were calculated. RESULTS The data
      of 413 patients were analyzed. Although INTEM CT was prolonged, significantly
      shorter CT and CFT, steeper alpha, and greater A10, MCF, and MCE were shown in
      patients age <3 months compared to older children. CONCLUSIONS Reference
      intervals of thromboelastometric evaluation for coagulation from pediatric
      patients with CHD were shown to have similar pattern to those obtained from
      healthy pediatric patients. Pediatric patients with CHD, even with cyanosis, were
      demonstrated to have functionally intact coagulation profile before surgery.

PMID- 27711025
TI  - Methotrexate and lung disease in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common chronic inflammatory disease affecting many
      tissues and resulting in substantial morbidity and increased mortality. Arthritis
      is the most notable clinical feature, but extra-articular features can have
      devastating consequences. Pulmonary manifestations are common in RA, with high
      rates of disease related lung disease and a propensity to pulmonary infections.
      Respiratory illness remains a leading cause of death among RA populations. Modern
      medicine greatly reduces the illness burden among patients with RA, particularly
      through the use of disease-modifying medications. Methotrexate is recommended as
      the first-line treatment of RA as it effectively reduces disease activity,
      morbidity and mortality. However, it has long been implicated as a causative
      agent in lung disease. The evidence for a cause and effect relationship in modern
      populations is contentious, but critically important. Increasing recognition of
      the importance and prevalence of interstitial lung disease in RA, and recent
      studies on the incidence of lung disease among RA and non-RA populations have
      cast doubt on the role of methotrexate as a causative agent. A correct
      understanding of the complex pulmonary disease processes in RA is crucial if we
      are to improve outcomes in this patient group. In this article we will discuss
      the epidemiology and characteristics of lung disease in rheumatoid arthritis and
      its possible relationship to methotrexate use.

PMID- 27711026
TI  - Preoperative functional assessment and optimization in surgical patient: changing
      the paradigm.
AB  - Functional capacity has been shown to be a major determinant of surgical outcome
      since it is related to postoperative complications, activity and daily function,
      level of independence and quality of life. Anesthesiologists as "perioperative
      physicians", can identify those scoring systems that assess functional capacity,
      whether from the basic physical history and walk test to the most complex such as
      cardiopulmonary exercise testing, and formulate intraoperative and postoperative
      interventions (rehabilitation) to minimize the impact of surgery on the recovery
      process. Nevertheless, the preoperative period can be used as an opportune time
      to increase functional reserve in anticipation of surgery, thus enabling the
      patient to better withstand the metabolic cost of surgical stress
      (prehabilitation). There is a compelling evidence that prehabilitation programs,
      including physical exercise, nutritional optimization and relaxation strategies,
      can enhance preoperative physiological reserve, however further studies are
      needed to identify the most appropriate protocols for those patients at risk, and
      assess the impact of such programs on clinically meaningful surgical outcomes.

PMID- 27711027
TI  - Quantification of the amount of dental material removed by selective grinding in
      wax dentures with photogrammetric measurements.
AB  - BACKGROUND: The use of photogrammetry may be a new method to quantify the amount
      of artificial dental material removed from the surface of each teeth during the
      grind procedure (SG). SG is necessary in each denture to reach a correct
      occlusion. It consists in a refine action on the prosthesis teeth's surface using
      milling machine tools, aimed to remove the interferences (pre-contacts) between
      upper and lower teeth during chewing. This measure is achieved after a comparison
      between pre and post-grinding 3D models. This new application could be of
      interest for both dentists and dental technicians because it could be used to
      evaluate, with a accurate numerical description, the action applied on teeth
      surfaces during the grinding process. Furthermore, results of the analysis could
      have some value for the dental industry, since the use of photogrammetry can
      improve the process, reducing costs during the design of artificial teeth and
      eventually this method could be used as a teaching tool both for dental and
      "dental technician" high school students. The purpose of this work is to measure
      the thickness of the artificial enamel removed during grinding phases. Usually,
      the dental technician adjusts the dental plate on the mount of the patient
      following the traditional method, without a quantitative evaluation of the
      material removed. The photogrammetric method (PM) proposed here allows to measure
      the amount of material removed during the grinding process. This measure is
      achieved after a comparison between pre and post-grinding 3D models. METHODS:
      Under control of three teachers (experts of dentures performed according to the
      Gerber method) ten complete dentures arrangements (upper and inferior arches)
      performed by dental students at the Prosthodontic Department of the University of
      Parma, Italy were analyzed with PM before and after SG. RESULTS: The average
      thickness variation between the pre and post-grinding dentures is within the
      range of 0.1/0.4 mm. For the upper arches, the mean value of the SG process is
      223 um while for the inferior arches is 240 um. Results show that the most
      important grind process in all models appear in correspondence of cusps, with
      values up to 1660 um. On the other hand, in correspondence of the fossae the
      results show a moderate grind action: the value is around 200-300 um. Conversely
      to guidelines thought to students: cusps undergo a greater grinding process than
      fossae, consequently cusps should be revisioned at least on their technical and
      morphological aspects. The average thickness variation between the pre and post
      grinding dentures is within the range of 0.1/0.4 mm, this mean an equal value
      loss of vertical dimension. Furthermore, the knowledge of the gauge material
      removed during the SG could be useful for dental industries, giving important
      information, that could be considered for project and design of artificial teeth.
      CONCLUSIONS: The FM implemented in this article has given satisfactory
      preliminary results, showing good accuracy, low costs and high versatility. It is
      necessary to highlight that this is an experimental method and that the present
      analysis is a pilot study that needs further evaluation. Nevertheless results
      obtained could be of some value for medical companies, in order to improve the
      artificial teeth's design and project. Moreover, such a method may serve as
      educational tool for dental students.

PMID- 27711028
TI  - Platelet-rich fibrin: a boon in regenerative endodontics.
AB  - Research into regenerative dentistry has contributed momentum to the field of
      molecular biology. Periapical surgery aims at removing periapical pathology to
      achieve complete wound healing and regeneration of bone and periodontal tissue.
      Regenerative endodontic procedures are widely being added to the current
      armamentarium of pulp therapy procedures. The regenerative potential of platelets
      has been deliberated. Platelet-rich fibrin (PRF) is a wonderful tissue
      engineering product and has recently gained much popularity due its promising
      results in wound healing bone induction. The features of this product are an
      attribute of platelets which, after cellular interactions, release growth factors
      and have shown application in diverse disciplines of dentistry. This paper is
      intended to shed light onto the various prospects of PRF and to provide clinical
      insight into regenerative endodontic therapy.

PMID- 27711029
TI  - Adipose tissue, obesity and non-alcoholic fatty liver disease.
AB  - The association of obesity with non-alcoholic fatty liver disease (NAFLD) has
      been established. Obesity has been linked not only to initial stages of the
      disease, i.e., simple steatosis (SS), but also to its severity. From an
      epidemiologic point of view, both diseases has an increasing prevalence
      worldwide. From a pathogenetic point of view, obesity and its associate IR
      contribute to the initial fat accumulation in the hepatocyte (SS), but also to
      the progression of SS to nonalcoholic steatohepatitis (NASH), NASH-related
      cirrhosis and hepatocellular carcinoma (HCC). From a clinical point of view,
      obesity has increased morbidity and mortality when combined with NAFLD, owing to
      cardiovascular and liver-specific mortality, including higher HCC risk. From a
      therapeutic point of view, weight loss is regarded as the cornerstone for the
      disease prevention and treatment. Although diet and exercise are the first choice
      to this aim, they are both difficult to achieve and sustain. Thus, the need for
      pharmacological treatment is considered of high importance. To treat obesity
      through pharmacologic weight loss, orlistat has been investigated, though with
      limited efficacy. Currently, liraglutide appears to be more efficacious, but it
      has not been officially approved for specifically NASH patients. Bariatric
      surgery is another alternative for severely obese patients showing histological
      improvement in NASH patients. However, since relative data from randomized trials
      are very limited, morbid obesity-related NASH patients may be subjected to
      bariatric surgery only after a careful individualized risk-benefit assessment.

PMID- 27711030
TI  - Systematic review on recent advances in the surgical management of rectal
      prolapse.
AB  - INTRODUCTION: Surgical management of external rectal prolapse (ERP) remains a
      challenge with the breadth of choices available and varies on the international,
      national, regional and locoregional level. Significant innovation has led to new
      techniques to manage ERP including changes to both abdominal and perineal
      approaches. EVIDENCE ACQUISITION: A systematic, English-language search of major
      databases was conducted from 2006-2016. From 636 papers two reviewers identified
      24 studies which compared two or more surgical techniques in adult patients with
      rectal prolapse and reported on complications, quality of life or recurrence. The
      Newcastle-Ottawa Scale (NOS) was used to score quality in non-randomized control
      trials (RCT) and the Cochrane Collaboration tool was use for RCTs. EVIDENCE
      SYNTHESIS: Abdominal and perianal surgeries both result in the resolution of
      symptoms and an improvement of quality of life for most patients. Short-term
      outcomes generally favored laparoscopy. Rectopexy with or without resection
      confers balances a low risk of recurrence with a similar complication rate to
      perineal surgery. The quality of included studies was general poor and most was
      at significant risk of bias. CONCLUSIONS: Most studies are of low quality and
      surgical management should be individualized to balance risk of the operation and
      the potential benefit to quality of life. Laparoscopy and modern anesthesia has
      made the abdominal approach more attractive even for elderly patients.

PMID- 27711031
TI  - State-Specific Prevalence of Current Cigarette Smoking and Smokeless Tobacco Use
      Among Adults - United States, 2014.
AB  - Tobacco use is the leading cause of preventable disease and death in the United
      States, resulting in approximately 480,000 premature deaths and more than $300
      billion in direct health care expenditures and productivity losses each year (1).
      In recent years, cigarette smoking prevalence has declined in many states;
      however, there has been relatively little change in the prevalence of current
      smokeless tobacco use or concurrent use of cigarettes and smokeless tobacco in
      most states, and in some states prevalence has increased (2). CDC analyzed data
      from the 2014 Behavioral Risk Factor Surveillance System (BRFSS) to assess state
      specific prevalence estimates of current use of cigarettes, smokeless tobacco,
      and cigarette and/or smokeless tobacco (any cigarette/smokeless tobacco use)
      among U.S. adults. Current cigarette smoking ranged from 9.7% (Utah) to 26.7%
      (West Virginia); current smokeless tobacco use ranged from 1.4% (Hawaii) to 8.8%
      (Wyoming); current use of any cigarette and/or smokeless tobacco product ranged
      from 11.3% (Utah) to 32.2% (West Virginia). Disparities in tobacco use by sex and
      race/ethnicity were observed; any cigarette and/or smokeless tobacco use was
      higher among males than females in all 50 states. By race/ethnicity, non-Hispanic
      whites had the highest prevalence of any cigarette and/or smokeless tobacco use
      in eight states, followed by non-Hispanic other races in six states, non-Hispanic
      blacks in five states, and Hispanics in two states (p<0.05); the remaining states
      did not differ significantly by race/ethnicity. Evidence-based interventions,
      such as increasing tobacco prices, implementing comprehensive smoke-free
      policies, conducting mass media anti-tobacco use campaigns, and promoting
      accessible smoking cessation assistance, are important to reduce tobacco use and
      tobacco-related disease and death among U.S. adults, particularly among
      subpopulations with the highest use prevalence (3).

PMID- 27711032
TI  - Announcement: National Bullying Prevention Awareness Month - October 2016.
AB  - Bullying among youths is defined as any unwanted aggressive behavior by another
      youth or group of youths who are not siblings or current dating partners and
      involves an observed or perceived power imbalance, and is repeated multiple times
      or is highly likely to be repeated (1). As a form of youth violence, bullying can
      include aggression that is physical (hitting or tripping), verbal (name calling
      or teasing), or relational/social (rumor spreading or leaving out of a group).
      Electronic aggression, or cyber-bullying, is bullying that occurs through the
      Internet, cellphone technology, and social media (e.g., e-mail, website, text
      messaging, posting videos, or pictures) (2).

PMID- 27711033
TI  - Update: Interim Guidance for Preconception Counseling and Prevention of Sexual
      Transmission of Zika Virus for Persons with Possible Zika Virus Exposure - United
      States, September 2016.
AB  - CDC has updated its interim guidance for persons with possible Zika virus
      exposure who are planning to conceive (1) and interim guidance to prevent
      transmission of Zika virus through sexual contact (2), now combined into a single
      document. Guidance for care for pregnant women with possible Zika virus exposure
      was previously published (3). Possible Zika virus exposure is defined as travel
      to or residence in an area of active Zika virus transmission
      (http://www.cdc.gov/zika/geo/index.html), or sex* without a condom? with a
      partner who traveled to or lived in an area of active transmission. Based on new
      though limited data, CDC now recommends that all men with possible Zika virus
      exposure who are considering attempting conception with their partner, regardless
      of symptom status,S wait to conceive until at least 6 months after symptom onset
      (if symptomatic) or last possible Zika virus exposure (if asymptomatic).
      Recommendations for women planning to conceive remain unchanged: women with
      possible Zika virus exposure are recommended to wait to conceive until at least 8
      weeks after symptom onset (if symptomatic) or last possible Zika virus exposure
      (if asymptomatic). Couples with possible Zika virus exposure, who are not
      pregnant and do not plan to become pregnant, who want to minimize their risk for
      sexual transmission of Zika virus should use a condom or abstain from sex for the
      same periods for men and women described above. Women of reproductive age who
      have had or anticipate future Zika virus exposure who do not want to become
      pregnant should use the most effective contraceptive method that can be used
      correctly and consistently. These recommendations will be further updated when
      additional data become available.

PMID- 27711034
TI  - Real-Time Monitoring of Vaccination Campaign Performance Using Mobile Phones -
      Nepal, 2016.
AB  - In 2012, the Global Vaccine Action Plan* established a goal to achieve measles
      and rubella elimination in five of the six World Health Organization (WHO)
      regions (194 countries) by 2020 (1). Measles elimination strategies aim to
      achieve >=95% coverage with 2 routine doses of measles-containing vaccine (2),
      and implement supplementary immunization activities (SIAs)? in settings where
      routine coverage is low or where there are subpopulations at high risk. To ensure
      SIA quality and to achieve >=95% SIA coverage nationally, rapid convenience
      monitoring (RCM) is used during or immediately after SIAs (3,4). The objective of
      RCM is to find unvaccinated children and to identify reasons for nonvaccination
      in areas with persons at high risk, to enable immediate implementation of
      corrective actions (e.g., reassigning teams to poorly vaccinated areas, modifying
      the timing of vaccination, or conducting mop-up vaccination activities). This
      report describes pilot testing of RCM using mobile phones (RCM-MP) during the
      second phase of an SIA in Nepal in 2016. Use of RCM-MP resulted in 87% timeliness
      and 94% completeness of data reporting and found that, although 95% of children
      were vaccinated, 42% of areas required corrective vaccination activities. RCM-MP
      challenges included connecting to mobile networks, small phone screen size, and
      capturing Global Positioning System (GPS) coordinates. Nonetheless, use of RCM-MP
      led to faster data transmission, analysis, and decision-making and to increased
      accountability among levels of the health system.

PMID- 27711035
TI  - Announcement: National Protect Your Hearing Month - October 2016.
AB  - October is National Protect Your Hearing Month, a time to raise awareness about
      the causes and prevention of noise-induced hearing loss. Noise-induced hearing
      loss results from sounds in the environment that are too loud and can damage
      sensitive structures in the inner ear, even with a brief exposure. This type of
      hearing loss can result from occupational noise exposures, leisure activities
      such as sporting events or concerts, or use of personal listening devices. Noise
      induced hearing loss is permanent and cannot be reversed (1).

PMID- 27711036
TI  - Vaccination Coverage Among Children Aged 19-35 Months - United States, 2015.
AB  - Sustained high coverage with recommended vaccinations among children has kept
      many vaccine-preventable diseases at low levels in the United States (1). To
      assess coverage with vaccinations recommended for children by age 2 years in the
      United States (2), CDC analyzed data collected by the 2015 National Immunization
      Survey (NIS) for children aged 19-35 months (born January 2012-May 2014).
      Overall, coverage did not change during 2014-2015. Coverage in 2015 was highest
      for >=3 doses of poliovirus vaccine (93.7%), >=3 doses of hepatitis B vaccine
      (HepB) (92.6%), >=1 dose of measles, mumps, and rubella vaccine (MMR) (91.9%),
      and >=1 dose of varicella vaccine (91.8%). The data were also examined for
      potential vaccination coverage differences by race/ethnicity, poverty status, and
      urbanicity. Although disparities were noted for each of these factors, the most
      striking differences were seen for poverty status. Children living below the
      federal poverty level* had lower coverage with most of the vaccinations assessed
      compared with children living at or above the poverty level; the largest
      disparities were for rotavirus vaccine (66.8% versus 76.8%), >=4 doses of
      pneumococcal conjugate vaccine (PCV) (78.9% versus 87.2%), the full series of
      Haemophilus influenzae type b vaccine (Hib) (78.1% versus 85.5%), and >=4 doses
      of diphtheria, tetanus, and acellular pertussis vaccine (DTaP) (80.2% versus
      87.1%). Although coverage was high in some groups, opportunities exist to
      continue to address disparities. Implementation of evidence-based interventions,
      including strategies to enhance access to vaccination services and systems
      strategies that can reduce missed opportunities, has the potential to increase
      vaccination coverage for children living below the poverty level and in rural
      areas (3).

PMID- 27711037
TI  - Vaccination Coverage Among Children in Kindergarten - United States, 2015-16
      School Year.
AB  - State-mandated vaccination requirements for school entry protect children and
      communities against vaccine-preventable diseases (1). Each school year, federally
      funded immunization programs (e.g., states, territories, jurisdictions) collect
      and report kindergarten vaccination data to CDC. This report describes
      vaccination coverage estimates in all 50 states and the District of Columbia
      (DC), and the estimated number of kindergartners with at least one vaccine
      exemption in 47 states and DC, during the 2015-16 school year. Median vaccination
      coverage* was 94.6% for 2 doses of measles, mumps and rubella vaccine (MMR);
      94.2% for diphtheria, tetanus, and acellular pertussis vaccine (DTaP); and 94.3%
      for 2 doses of varicella vaccine. MMR coverage increased in 32 states during the
      last year, and 22 states reported coverage >=95% (2). A total of 45 states and DC
      had either a grace period allowing students to attend school before providing
      documentation of vaccination or provisional enrollment that allows
      undervaccinated students to attend school while completing a catch-up schedule.
      Among the 23 states that were able to voluntarily report state-level data on
      grace period or provisional enrollment to CDC, a median of 2.0% of kindergartners
      were not documented as completely vaccinated and were attending school within a
      grace period or were provisionally enrolled. The median percentage of
      kindergartners with an exemption from one or more vaccinations? was 1.9%. State
      and local immunization programs, in cooperation with schools, can improve
      vaccination coverage by ensuring that all kindergartners are vaccinated during
      the grace period or provisional enrollment.

PMID- 27711038
TI  - Prevalence of Severe Joint Pain Among Adults with Doctor-Diagnosed Arthritis -
      United States, 2002-2014.
AB  - In the United States, arthritis is a leading cause of disability (1,2); arthritis
      affected an estimated 52.5 million (22.7%) adults in 2010-2012 and has been
      projected to affect 78.4 million adults by 2040 (3). Severe joint pain (SJP) can
      limit function and seriously compromise quality of life (4,5). To determine the
      prevalence of SJP among adults with doctor-diagnosed arthritis, and the trend in
      SJP from 2002 to 2014, CDC analyzed data from the National Health Interview
      Survey. In 2014, approximately one fourth of adults with arthritis had SJP
      (27.2%). Within selected groups, the age-standardized prevalence of SJP was
      higher among women (29.2%), non-Hispanic blacks (42.3%), Hispanics (35.8%), and
      persons with a disability (45.6%), and those who were unable to work (51.9%);
      prevalence also was higher among those who had fair or poor health (49.1%),
      obesity (31.7%), heart disease (34.1%), diabetes (40.9%), or serious
      psychological distress (56.3%). From 2002 to 2014, the age-standardized
      prevalence of SJP among adults with arthritis did not change (p = 0.14); however,
      the number of adults with SJP was significantly higher in 2014 (14.6 million)
      than in 2002 (10.5 million). A strategy to improve pain management (e.g., the
      2016 National Pain Strategy*) has been developed, and more widespread
      dissemination of evidence-based interventions that reduce joint pain in adults
      with arthritis might reduce the prevalence of SJP.

PMID- 27711039
TI  - QuickStats: Percentage* of Children Aged 1-5 Years with Elevated Blood Lead
      Levels,? by Race/EthnicityS - National Health and Nutrition Examination Survey,
      United States, 1988-1994, 1999-2006, and 2007-2014.
AB  - From 1988-1994 to 2007-2014, the percentage of children aged 1-5 years with blood
      lead levels >=5 MUg/dL declined from 25.6% to 1.9%. Blood lead levels fell
      dramatically for all racial and ethnic groups. Despite the decline, in 2007-2014,
      non-Hispanic black children (4.0%) aged 1-5 years were twice as likely as non
      Hispanic white children (1.9%) and more than three times as likely as Mexican
      American children (1.1%) to have elevated blood lead levels.

PMID- 27711040
TI  - Notice to Readers: Update to Reporting of Pneumonia and Influenza Mortality.
AB  - The current issue of MMWR (week 39) will be the last to include data from the 122
      Cities Mortality Reporting System (122 CMRS) in Notifiable Disease and Mortality
      Tables, Table III ("Deaths in 122 cities"
      [http://www.cdc.gov/mmwr/volumes/65/wr/mm6539md.htm?s_cid=mm6539md_w#table-17]).
      Beginning in the publication for the week ending October 8, 2016 (week 40), data
      from the National Center for Health Statistics (NCHS) Mortality Surveillance
      System will replace the information reported in Table III, and the 122 Cities
      Mortality Reporting System (122 CMRS) will be retired. The NCHS Mortality
      Surveillance System provides improvements in the data, including reports by the
      week of death and a consistent pneumonia and influenza (P&I) case definition
      across all sites. These improvements, along with recent and continuing increases
      in the timeliness of death certificate data, have led CDC to update the P&I
      mortality surveillance platform from the 122 CMRS to the NCHS Mortality
      Surveillance System.

PMID- 27711041
TI  - Characteristics of Children Aged <18 Years with Zika Virus Disease Acquired
      Postnatally - U.S. States, January 2015-July 2016.
AB  - Zika virus is an emerging mosquito-borne flavivirus that typically causes an
      asymptomatic infection or mild illness, although infection during pregnancy is a
      cause of microcephaly and other serious brain abnormalities. Guillain-Barre
      syndrome and other neurologic complications can occur in adults after Zika virus
      infection. However, there are few published reports describing postnatally
      acquired Zika virus disease among children. During January 2015-July 2016, a
      total of 158 cases of confirmed or probable postnatally acquired Zika virus
      disease among children aged <18 years were reported to CDC from U.S. states. The
      median age was 14 years (range = 1 month-17 years), and 88 (56%) were female. Two
      (1%) patients were hospitalized; none developed Guillain-Barre syndrome, and none
      died. All reported cases were travel-associated. Overall, 129 (82%) children had
      rash, 87 (55%) had fever, 45 (29%) had conjunctivitis, and 44 (28%) had
      arthralgia. Health care providers should consider a diagnosis of Zika virus
      disease in children who have an epidemiologic risk factor and clinically
      compatible illness, and should report cases to their state or local health
      department.

PMID- 27711042
TI  - The effects of human milk fortification on nutrients and milk properties.
AB  - OBJECTIVE: To investigate the effects of fortification and storage on nutrients
      and properties of various human milk (HM) types. STUDY DESIGN: Mother's own milk
      (MOM) and pasteurized donor human milk (DHM; n=118) were analyzed pre- and post
      fortification with Enfamil and Similac human milk fortifier (EHMF and SHMF)
      before and after 24 h of refrigerated storage. RESULTS: Milk fortified with SHMF
      had significantly greater osmolality, pH and lipase activity than EHMF. Changes
      in protein, pH and osmolality following refrigerated storage differed between
      fortifiers. When milk type was factored into the analysis, protein and lipase
      activity changes in fresh MOM differed significantly from DHM and frozen MOM.
      Analysis of UNF HM found higher protein levels in preterm vs term samples and in
      MOM vs DHM. CONCLUSION: Nutrient composition of HM varies significantly by milk
      type. Although fortifiers enhance select nutrients, each has the potential to
      affect HM properties in a unique way and these affects may vary by milk type.

PMID- 27711043
TI  - Right ventricular performance using myocardial deformation imaging in infants
      with bronchopulmonary dysplasia.
AB  - OBJECTIVE: Right ventricular (RV) performance among infants with bronchopulmonary
      dysplasia (BPD) remains poorly understood. We tested the hypothesis that
      myocardial deformation imaging (MDI) strain and strain rate would allow for
      differentiation between infants with severe and milder forms of BPD, independent
      of tissue Doppler imaging (TDI) and superior to conventional echocardiographic
      measurements. STUDY DESIGN: Infants with various severities of BPD (11 with none
      or mild, 13 with moderate and 10 with severe) underwent conventional
      echocardiography, TDI and MDI assessments at >36 weeks of corrected gestational
      age. BPD severity grading was determined according to the National Institutes of
      Child Health and Disease workshop rating scale by physicians blinded to the
      echocardiogram results. Group data were compared with one-way analysis of
      variance or Kruskal-Wallis tests, with post hoc multiple comparisons. RESULTS: No
      differences in traditional echocardiographic parameters or TDI among the three
      BPD severity groups were observed; none of the infants had evidence of pulmonary
      hypertension. Using MDI, infants with severe BPD had lower peak global systolic
      strain than did infants with moderate BPD (P<0.01) or mild/none BPD (P<0.01).
      Early and late diastolic strain rate measurements were similar across the three
      groups. CONCLUSIONS: Among infants with severe forms of BPD, evidence of abnormal
      RV systolic function was detected with MDI, but not traditional echocardiographic
      or TDI measurements. Infants with severe forms of BPD may represent a
      particularly high-risk subgroup for decreased RV performance warranting cardiac
      surveillance. MDI should be considered as a method to quantitate RV function in
      this population.

PMID- 27711044
TI  - Evaluation of the management of pregnancies and infants at risk for congenital
      syphilis: La Reunion, 2008 to 2014.
AB  - OBJECTIVE: To evaluate the maternal-fetal management and follow-up of infants at
      risk for congenital syphilis. STUDY DESIGN: Monocentric retrospective cohort
      study at the Felix Guyon Hospital, Saint-Denis, La Reunion between January 2008
      and December 2014. Management of 38 pregnancies (35 women, 39 fetuses) with a
      positive syphilis serology was evaluated according to the Centers for Disease
      Control and Prevention (CDC) guidelines. RESULTS: A total of 68% (n=26) of
      pregnancies were screened before 16 weeks of gestation, and 26% (n=10) had
      appropriate treatment. Adverse outcomes were noted in 45% of pregnancies.
      Neonatal serology was not performed in 7 live-born neonates (19%) and 33 infants
      were classifiable according to the four CDC scenarios. In the infants, adequate
      complementary evaluation and appropriate treatment were noted in 42% (n=13) and
      55% (n=17) of cases, respectively. Rate of infant follow-up was 76% (n=16). No
      treatment failure was observed in infants. CONCLUSION: Reinforcement of public
      health policies and a better sensitization, training and collaboration among
      perinatal caregivers are warranted given the gaps revealed in our study.

PMID- 27711046
TI  - Histone Lysine Demethylases of JMJD2 or KDM4 Family are Important Epigenetic
      Regulators in Reward Circuitry in the Etiopathology of Depression.
AB  - Major depressive disorder (MDD) is debilitating mental illness and is one of the
      leading contributors to global burden of disease, but unfortunately newer and
      better drugs are not forthcoming. The reason is lack of complete understanding of
      molecular mechanisms underlying the development of this disorder. Recent research
      shows dysregulation in epigenetic regulatory mechanisms, particularly the
      transcriptionally repressive di- and tri-methylation of histone 3 lysine 9
      (H3K9me2/me3) in nucleus accumbens (NAc), a critical region of the reward pathway
      involved in the development of anhedonia, the hallmark of depression. However,
      the role of histone lysine demethylases, which can remove methylation from H3K9,
      in particular Jumonji domain containing demethylases 2 or Jmjd2 family, has not
      been studied. Using social defeat stress-induced mouse model of depression, this
      study uncovered that transcripts of most of the Jmjd2 members were unchanged
      after 5 days of defeat during the onset of depression, but were downregulated
      after 10 days of defeat in full-blown depression. Blocking the Jumonji domain
      containing demethylases by chronic administration of inhibitors
      dimethyloxalylglycine (DMOG) and ML324 resulted in depression-like phenotype even
      in absence of stress exposure, which was associated with an increase in
      transcriptionally repressive epigenetic marks H3K9me2/me3 in NAc, causing altered
      neuroplastic changes as reported in NAc in depression models. Thus, we report for
      the first time that Jmjd2 class demethylases are critical epigenetic regulators
      involved in etiopathology of depression and related disorders and activation of
      these demethylases can be a good strategy in the treatment of MDD and related
      psychiatric disorders.

PMID- 27711045
TI  - Non-invasive inhaled nitric oxide in the treatment of hypoxemic respiratory
      failure in term and preterm infants.
AB  - OBJECTIVES: Inhaled nitric oxide (iNO) is effective in conjunction with tracheal
      intubation (TI) and mechanical ventilation (MV) for treating arterial pulmonary
      hypertension and hypoxemic respiratory failure (HRF) in near-term and term
      newborns. Non-invasive respiratory support with nasal continuous positive airway
      pressure (CPAP) is increasingly used to avoid morbidity associated with TI and
      MV, yet the effectiveness of iNO delivery via nasal CPAP remains unknown. To
      evaluate the effectiveness of iNO delivered via the bubble nasal CPAP system in
      term and preterm newborns with HRF. STUDY DESIGN: Electronic medical records from
      all infants admitted to the neonatal intensive care unit (NICU) during 2005 to
      2014 (n=10, 895) were screened for treatment with iNO therapy for HRF. Detailed
      data on population characteristics and cardiorespiratory, iNO and respiratory
      support indices were abstracted for all infants, who were administered iNO non
      invasively using bubble nasal CPAP. Change in relevant indices at baseline
      (before initiating non-invasive iNO) and at 3, 6, 12 and 24 h after non-invasive
      iNO therapy were analyzed using repeated measures analysis of variance. RESULTS:
      Of 795 infants treated with iNO (7.3% of total NICU admissions) over a 10-year
      period, 107 infants (13.4% of iNO treated) with birth weight 2448+/-1112 g and
      gestational age 35.3+/-5.8 weeks received iNO non-invasively. 25 infants received
      iNO exclusively non-invasively, whereas in remaining 82 infants non-invasive
      route followed invasive delivery via TI and MV. Indications for using non
      invasive iNO included idiopathic pulmonary hypertension (39%), congenital heart
      disease (37%), bronchopulmonary dysplasia (10%), meconium aspiration syndrome
      (9%) and congenital diaphragmatic hernia (5%). Over the 24 h following initiation
      of non-invasive iNO, fractional oxygen requirements decreased (0.38 to 0.32;
      P<0.0005) and SpO2 increased (90.7 to 91.6%; P<0.01) with no significant changes
      in heart rate, respiratory rate, blood pressure, pH and PaCO2. On average non
      invasive iNO was initiated on day of life 9 with a maximal dose was 20 p.p.m. The
      average duration of iNO therapy and the duration over which it was weaned off
      were 134 and 51 h, respectively. Analysis of environmental gases during non
      invasive iNO therapy revealed median ambient nitrogen dioxide and nitric oxide
      levels of 0.30 and 0.01 p.p.m., respectively. CONCLUSIONS: Initiation of iNO in
      infants on bubble nasal CPAP or continuation of iNO in infants transitioning from
      MV to bubble nasal CPAP is associated with improved oxygenation during HRF in
      term and preterm infants. Non-invasive iNO may have a synergistic effect with
      airway recruitment strategies such as nasal CPAP.

PMID- 27711047
TI  - The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge
      like Eating in Rats.
AB  - Compulsive, binge eating of highly palatable food constitutes a core feature of
      some forms of obesity and eating disorders, as well as of the recently proposed
      disorder of food addiction. Trace amine-associated receptor 1 (TAAR1) is a highly
      conserved G-protein-coupled receptor bound by endogenous trace amines. TAAR1
      agonists have been shown to reduce multiple behavioral effects of drugs of abuse
      through their actions on the mesocorticolimbic system. In this study, we
      hypothesized that TAAR1 may have a role in compulsive, binge-like eating; we
      tested this hypothesis by assessing the effects of a TAAR1 agonist, RO5256390, in
      multiple excessive feeding-related behaviors induced by limiting access to a
      highly palatable diet in rats. Our results show that RO5256390 blocked binge-like
      eating in rats responding 1 h per day for a highly palatable sugary diet.
      Consistent with a palatability-selective effect, drug treatment selectively
      reduced the rate and regularity of palatable food responding, but it did not
      affect either baseline intake or food restriction-induced overeating of the
      standard chow diet. Furthermore, RO5256390 fully blocked compulsive-like eating
      when the palatable diet was offered in an aversive compartment of a light/dark
      conflict box, and blocked the conditioned rewarding properties of palatable food,
      as well as palatable food-seeking behavior in a second-order schedule of
      reinforcement. Drug treatment had no effect on either anxiety-like or depressive
      like behavior, and it did not affect control performance in any of the tests.
      Importantly, rats exposed to palatable food showed decreased TAAR1 levels in the
      medial prefrontal cortex (mPFC), and RO5256390 microinfused into the infralimbic,
      but not prelimbic, subregion of the mPFC-reduced binge-like eating. Altogether,
      these results provide evidence for TAAR1 agonism as a novel pharmacological
      treatment for compulsive, binge eating.

PMID- 27711048
TI  - A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel
      Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with
      Autism Spectrum Disorder.
AB  - The core symptoms of autism spectrum disorder (ASD) include impaired social
      communication, repetitive behaviors, and restricted interests. No effective
      pharmacotherapy for these core deficits exists. Within the domain of social
      communication, the vasopressin system is implicated in social cognition and
      social signaling deficits of ASD, and represents a potential therapeutic target.
      We assessed the effects of a single 20 mg intravenous dose of the arginine
      vasopressin receptor 1A (V1a) antagonist, RG7713, on exploratory biomarkers (eye
      tracking), behavioral and clinical measures of social cognition and communication
      (affective speech recognition (ASR), reading the mind in the eyes, olfactory
      identification, scripted interaction), and safety and tolerability in a
      multicenter, randomized, double-blind, placebo-controlled, cross-over study of 19
      high-functioning adult male subjects with DSM-IV Autistic Disorder (age 18-45
      years; full scale IQ >70; ABC-Irritability subscale ?13). Eye-tracking showed an
      increase in biological motion orienting preference with RG7713 (ES=0.8, p=0.047)
      and a non-significant improvement in the composite score (ES=0.2, p=0.29). RG7713
      reduced ability to detect lust (ES=-0.8, p=0.03) and fear (ES=-0.7, p=0.07) in
      ASR. However, when all eight individual emotion subscales were combined into an
      overall ASR performance score, the reduction was non-significant (ES=-0.1,
      p=0.59). Thirteen adverse events were reported in 10 subjects; all were of mild
      (11/13) or moderate (2/13) severity. Although interpretation should be cautious
      due to multiple comparisons and small sample size, these results provide
      preliminary evidence from experimental and behavioral biomarkers, that blockade
      of the V1a receptor may improve social communication in adults with high
      functioning ASD. ClinicalTrials.gov identifier: NCT01474278 A Study of RO5028442
      in Adult Male High-Functioning Autistic Patients. Available at:
      https://clinicaltrials.gov/ct2/show/NCT01474278.

PMID- 27711049
TI  - Clozapine Modulates Glucosylceramide, Clears Aggregated Proteins, and Enhances
      ATG8/LC3 in Caenorhabditis elegans.
AB  - Defining the mechanisms of action of the antipsychotic drug (APD), clozapine, is
      of great importance, as clozapine is more effective and has therapeutic benefits
      in a broader range of psychiatric disorders compared with other APDs. Its range
      of actions have not been fully characterized. Exposure to APDs early in
      development causes dose-dependent developmental delay and lethality in
      Caenorhabditis elegans. A previous genome-wide RNAi screen for suppressors of
      clozapine-induced developmental delay and lethality revealed 40 candidate genes,
      including sms-1, which encodes a sphingomyelin synthase. One sms-1 isoform is
      expressed in the C. elegans pharynx, and its transgene rescues the sms-1 mutant
      phenotype. We examined pharyngeal pumping and observed that clozapine-induced
      inhibition of pharyngeal pumping requires sms-1, a finding that may explain the
      role of the gene in mediating clozapine-induced developmental delay/lethality. By
      analyzing multiple enzymes involved in sphingolipid metabolism, and by observing
      the effect of addition of various lipids directly to the worms, we suggest that
      glucosylceramide may be a key mediator of the effects of clozapine. We further
      observed that clozapine clears protein aggregates, such as alpha-synuclein, PolyQ
      protein, and alpha-1-antitrypsin mutant protein. In addition, it enhances
      ATG8/LC3. We conclude that clozapine appears to affect the development and induce
      lethality of worms, in part, through modulating glucosylceramide. We discuss the
      possible connections among glucosylceramide, protein aggregate clearance, and
      autophagy. Interactions, including mechanistic pathways involving these elements,
      may underlie some of the clinical effects of clozapine.

PMID- 27711050
TI  - Preparing monodisperse macromolecular samples for successful biological small
      angle X-ray and neutron-scattering experiments.
AB  - Small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) are
      techniques used to extract structural parameters and determine the overall
      structures and shapes of biological macromolecules, complexes and assemblies in
      solution. The scattering intensities measured from a sample contain contributions
      from all atoms within the illuminated sample volume, including the solvent and
      buffer components, as well as the macromolecules of interest. To obtain
      structural information, it is essential to prepare an exactly matched solvent
      blank so that background scattering contributions can be accurately subtracted
      from the sample scattering to obtain the net scattering from the macromolecules
      in the sample. In addition, sample heterogeneity caused by contaminants,
      aggregates, mismatched solvents, radiation damage or other factors can severely
      influence and complicate data analysis, so it is essential that the samples be
      pure and monodisperse for the duration of the experiment. This protocol outlines
      the basic physics of SAXS and SANS, and it reveals how the underlying conceptual
      principles of the techniques ultimately 'translate' into practical laboratory
      guidance for the production of samples of sufficiently high quality for
      scattering experiments. The procedure describes how to prepare and characterize
      protein and nucleic acid samples for both SAXS and SANS using gel
      electrophoresis, size-exclusion chromatography (SEC) and light scattering. Also
      included are procedures that are specific to X-rays (in-line SEC-SAXS) and
      neutrons, specifically preparing samples for contrast matching or variation
      experiments and deuterium labeling of proteins.

PMID- 27711051
TI  - Serial sequencing of isolength RAD tags for cost-efficient genome-wide profiling
      of genetic and epigenetic variations.
AB  - Isolength restriction site-associated DNA (isoRAD) sequencing is a very simple
      but powerful approach that was originally developed for genome-wide genotyping at
      minimal labor and cost, and it has recently extended its applicability to allow
      quantification of DNA methylation levels. The isoRAD method is distinct from
      other genotyping-by-sequencing (GBS) methods because of its use of special
      restriction enzymes to produce isolength tags (32-36 bp), and sequencing of these
      uniform tags can bring many benefits. However, the relatively short tags produced
      by the original protocol are mostly suited to single-end (SE) sequencing (36-50
      bp), and therefore they cannot efficiently match the gradually increased
      sequencing capacity of next-generation sequencing (NGS) platforms. To address
      this issue, we describe an advanced protocol that allows the preparation of five
      concatenated isoRAD tags for Illumina paired-end (PE) sequencing (100-150 bp).
      The configuration of the five concatenated tags is highly flexible, and can be
      defined by users to work with a desired combination of samples and/or restriction
      enzymes to suit specific research purposes. In comparison with the original
      protocol, the advanced protocol has an additional digestion and ligation step,
      and library preparation can be completed in ~8 h.

PMID- 27711052
TI  - Remodeling somatic nuclei via exogenous expression of protamine 1 to create
      spermatid-like structures for somatic nuclear transfer.
AB  - This protocol describes how to convert the chromatin structure of sheep and mouse
      somatic cells into spermatid-like nuclei through the heterologous expression of
      the protamine 1 gene (Prm1). Furthermore, we also provide step-by-step
      instructions for somatic cell nuclear transfer (SCNT) of Prm1-remodeled somatic
      nuclei in sheep oocytes. There is evidence that changing the organization of a
      somatic cell nucleus with that which mirrors the spermatozoon nucleus leads to
      better nuclear reprogramming. The protocol may have further potential application
      in determining the protamine and histone footprints of the whole genome;
      obtaining 'gametes' from somatic cells; and furthering understanding of the
      molecular mechanisms regulating the maintenance of DNA methylation in imprinted
      control regions during male gametogenesis. The protocol is straightforward, and
      it requires 4 weeks from the establishment of the cell lines to their
      transfection and the production of cloned blastocysts. It is necessary for
      researchers to have experience in cell biology and embryology, with basic skills
      in molecular biology, to carry out the protocol.

PMID- 27711053
TI  - Modeling and correction of structural variations in patient-derived iPSCs using
      CRISPR/Cas9.
AB  - Genome engineering technology using engineered nucleases has been rapidly
      developing, enabling the efficient correction of simple mutations. However, the
      precise correction of structural variations (SVs) such as large inversions
      remains limited. Here we describe a detailed procedure for the modeling or
      correction of large chromosomal rearrangements and short nucleotide repeat
      expansions using engineered nucleases in human induced pluripotent stem cells
      (hiPSCs) from a healthy donor and patients with SVs. This protocol includes the
      delivery of engineered nucleases with no donor template to hiPSCs, and genotyping
      and derivation/characterization of gene-manipulated hiPSC clones. With engineered
      nucleases, genomic inversions, reversions, and deletions of short nucleotide
      expansions can be identified in 2 weeks, and desired clones can be generated in
      as little as 3-4 weeks. This protocol enables the correction of large inverted
      segments and short nucleotide repeat expansions in diseases such as hemophilia A,
      fragile X syndrome, Hunter syndrome, and Friedreich's ataxia.

PMID- 27711055
TI  - Reservoirs of resistance: To understand why antibiotics fail, geneticists chase
      the 'resistome'.

PMID- 27711054
TI  - The scaffold protein Tks4 is required for the differentiation of mesenchymal
      stromal cells (MSCs) into adipogenic and osteogenic lineages.
AB  - The commitment steps of mesenchymal stromal cells (MSCs) to adipogenic and other
      lineages have been widely studied but not fully understood. Therefore, it is
      critical to understand which molecules contribute to the conversion of stem cells
      into differentiated cells. The scaffold protein Tks4 plays a role in podosome
      formation, EGFR signaling and ROS production. Dysfunction of Tks4 causes a
      hereditary disease called Frank-ter Haar syndrome with a variety of defects
      concerning certain mesenchymal tissues (bone, fat and cartilage) throughout
      embryogenic and postnatal development. In this study, we aimed to analyze how the
      mutation of Tks4 affects the differentiation potential of multipotent bone marrow
      MSCs (BM-MSCs). We generated a Tks4 knock-out mouse strain on C57Bl/6 background,
      and characterized BM-MSCs isolated from wild type and Tks4-/- mice to evaluate
      their differentiation. Tks4-/- BM-MSCs had reduced ability to differentiate into
      osteogenic and adipogenic lineages compared to wild type. Studying the expression
      profile of a panel of lipid-regulated genes during adipogenic induction revealed
      that the expression of adipogenic transcription factors, genes responsible for
      lipid droplet formation, sterol and fatty acid metabolism was delayed or reduced
      in Tks4-/- BM-MSCs. Taken together, these results establish a novel function for
      Tks4 in the regulation of MSC differentiation.

PMID- 27711056
TI  - SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease
      activity.

PMID- 27711057
TI  - Corrigendum: High-throughput epitope discovery reveals frequent recognition of
      neo-antigens by CD4+ T cells in human melanoma.

PMID- 27711058
TI  - Of mice and interaction: A new way to investigate complex genetic traits.

PMID- 27711059
TI  - A broader spectrum of tuberculosis.

PMID- 27711060
TI  - Picture imperfect: Going beyond imaging amyloid in Alzheimer's disease.

PMID- 27711061
TI  - Blocking fatty acid synthesis reduces lung tumor growth in mice.

PMID- 27711062
TI  - Reducing the silence.

PMID- 27711064
TI  - Where are the data?

PMID- 27711065
TI  - Corrigendum: Blocking c-Met-mediated PARP1 phosphorylation enhances anti-tumor
      effects of PARP inhibitors.

PMID- 27711063
TI  - Signals from the gut microbiota to distant organs in physiology and disease.
AB  - The ecosystem of the human gut consists of trillions of bacteria forming a
      bioreactor that is fueled by dietary macronutrients to produce bioactive
      compounds. These microbiota-derived metabolites signal to distant organs in the
      body, which enables the gut bacteria to connect to the immune and hormone system,
      to the brain (the gut-brain axis) and to host metabolism, as well as other
      functions of the host. This microbe-host communication is essential to maintain
      vital functions of the healthy host. Recently, however, the gut microbiota has
      been associated with a number of diseases, ranging from obesity and inflammatory
      diseases to behavioral and physiological abnormalities associated with
      neurodevelopmental disorders. In this Review, we will discuss microbiota-host
      cross-talk and intestinal microbiome signaling to extraintestinal organs. We will
      review mechanisms of how this communication might contribute to host physiology
      and discuss how misconfigured signaling might contribute to different diseases.

PMID- 27711067
TI  - Reply to SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease
      activity.

PMID- 27711066
TI  - Corrigendum: Adjuvant-dependent innate and adaptive immune signatures of risk of
      SIVmac251 acquisition.

PMID- 27711068
TI  - Corrigendum: Inter-individual variability and genetic influences on cytokine
      responses to bacteria and fungi.

PMID- 27711069
TI  - Rifaximin, Microbiota Biology, and Hepatic Encephalopathy.
AB  - Rifaximin is beneficial in the treatment of minimal hepatic encephalopathy (MHE).
      Kang et al. (Clin Transl Gastroenterol 7: e187; doi:10.1038/ctg.2016.44)
      investigated the effects of rifaximin in a mouse model of MHE-associated
      microbiota without concomitant liver disease. In addition to some impact on the
      composition of microbiota, rifaximin altered bacterial functions, ameliorated
      local and systemic inflammation, and reduced enterocyte glutaminase activity. We
      discuss these effects as well as the interpretation of the permeability studies,
      given the potential interaction of dysbiosis with dysfunctional intestinal
      barrier, leading to systemic inflammation and increased uptake of bacterial
      metabolites that contribute to MHE in the presence of hepatic dysfunction.

PMID- 27711070
TI  - Universal tumor screening for Lynch syndrome: health-care providers'
      perspectives.
AB  - PURPOSE: Population-based reflex testing of colorectal tumors can identify
      individuals with Lynch syndrome (LS), but there is debate regarding the type of
      patient discretion such a program warrants. We examined health-care providers'
      views and experiences to inform the design of a reflex-testing program and their
      perspectives regarding an opt-out option. METHODS: We interviewed providers
      managing LS or colorectal cancer patients, including surgeons, genetic
      counselors, oncologists, primary-care physicians, and gastroenterologists.
      Qualitative data were analyzed thematically using constant comparison techniques.
      RESULTS: Providers supported a reflex-testing program because of the current lack
      of coordinated immunohistochemistry (IHC) testing and underascertainment of LS
      patients as well as the opportunity to standardize the increasing use of genomic
      tests in practice. Most supported an opt-out after reflex testing because they
      felt that IHC is akin to other pathology tests, which are not optional. Some
      favored an opt-out before testing because of concern for patients experiencing
      distress, insurance discrimination, or a diagnostic odyssey that may be
      inconclusive. CONCLUSION: Providers support a reflex-testing program to improve
      the identification and management of suspected LS patients. However, how to
      support meaningful information provision to enable an opt-out without
      jeopardizing testing uptake and the anticipated public health benefits remains a
      policy challenge.Genet Med advance online publication 06 October 2016.

PMID- 27711071
TI  - Increasing the sensitivity of clinical exome sequencing through improved
      filtration strategy.
AB  - BACKGROUND: Clinical exome sequencing (CES) has greatly improved the diagnostic
      process for individuals with suspected genetic disorders. However, the majority
      remains undiagnosed after CES. Although understanding potential reasons for this
      limited sensitivity is critical for improving the delivery of clinical genomics,
      research in this area has been limited. MATERIALS AND METHODS: We first
      calculated the theoretical maximum sensitivity of CES by analyzing >100 families
      in whom a Mendelian phenotype is mapped to a single locus. We then tested the
      hypothesis that positional mapping can limit the search space and thereby
      facilitate variant interpretation by reanalyzing 33 families with "negative" CES
      and applying positional mapping. RESULTS: We found that >95% of families who map
      to a single locus harbored genic (as opposed to intergenic) variants that are
      potentially identifiable by CES. Our reanalysis of "negative" CES revealed likely
      causal variants in the majority (88%). Several of these solved cases have
      undergone negative whole-genome sequencing. CONCLUSION: The discrepancy between
      the theoretical maximum and the actual clinical sensitivity of CES is primarily
      in the variant filtration rather than the variant capture and sequencing phase.
      The solution to negative CES is not necessarily in expanding the coverage but
      rather in devising approaches that improve variant filtration. We suggest that
      positional mapping is one such approach.Genet Med advance online publication 06
      October 2016.

PMID- 27711072
TI  - Numerous Brugada syndrome-associated genetic variants have no effect on J-point
      elevation, syncope susceptibility, malignant cardiac arrhythmia, and all-cause
      mortality.
AB  - PURPOSE: We investigated whether Brugada syndrome (BrS)-associated variants
      identified in the general population have an effect on J-point elevation as well
      as whether carriers of BrS variants were more prone to experience syncope and
      malignant ventricular arrhythmia and had increased mortality compared with
      noncarriers. METHODS: All BrS-associated variants were identified using the Human
      Gene Mutation Database (HGMD). Individuals were randomly selected from a general
      population study using whole-exome sequencing data (n = 870) and genotype array
      data (n = 6,161) and screened for BrS-associated variants. Electrocardiograms
      (ECG) were analyzed electronically, and data on syncope, ventricular arrhythmias,
      and mortality were obtained from administrative health-care registries. RESULTS:
      In HGMD, 382 BrS-associated genetic variants were identified. Of these, 28
      variants were identified in the study cohort. None of the carriers presented with
      type 1 BrS ECG pattern. Mean J-point elevation in V1 and V2 were within normal
      guideline limits for carriers and noncarriers. There was no difference in syncope
      susceptibility (carriers 8/624; noncarriers 98/5,562; P = 0.51), ventricular
      arrhythmia (carriers 4/620; noncarriers 9/5,524; P = 0.24), or overall mortality
      (hazard ratio 0.93, 95% CI 0.63-1.4). CONCLUSIONS: Our data indicate that a
      significant number of BrS-associated variants are not the monogenic cause of
      BrS.Genet Med advance online publication 06 October 2016.

PMID- 27711074
TI  - P300/CBP-associated factor (PCAF) inhibits the growth of hepatocellular carcinoma
      by promoting cell autophagy.
AB  - Aberrant autophagic processes have been found to have fundamental roles in the
      pathogenesis of different kinds of tumors, including hepatocellular carcinoma
      (HCC). P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT),
      performs its function by acetylating both histone and non-histone proteins. Our
      previous studies showed that PCAF was downregulated in HCC tissues and its high
      expression was significantly associated with patient survival after surgery,
      serving as a prognostic marker. In this study we found that overexpression of
      PCAF induced autophagy of HCC cells and its knockdown depressed autophagy. As
      type II programmed cell death, autophagy induced by PCAF-elicited cell death in
      HCC cells. In vivo experiments confirmed that PCAF-induced autophagy inhibited
      tumor growth. Subsequent in vitro experiments showed that PCAF promoted autophagy
      by inhibiting Akt/mTOR signaling pathway. Our findings show that PCAF is a novel
      modulator of autophagy in HCC, and can serve as an attractive therapeutic
      strategy of HCC treatment.

PMID- 27711075
TI  - Stat3 modulates chloride channel accessory protein expression in normal and
      neoplastic mammary tissue.
AB  - Mammary gland regression at the cessation of lactation (involution) is an
      exquisitely orchestrated process of cell death and tissue remodelling in which
      Stat3 signalling has an essential role. The involution microenvironment of the
      mammary gland is considered to be pro-tumourigenic and a proportion of cases of
      pregnancy-associated breast cancer are suggested to originate in tandem with
      involution. However, the apparent paradox that STAT3 is required for cell death
      in normal mammary gland, but is associated with breast cancer cell survival, has
      not been resolved. Herein, we investigate Stat3-mediated regulation of expression
      of members of the calcium-activated chloride channel regulator (CLCA) family of
      proteins during involution and mammary carcinogenesis. Using the conditionally
      immortal mammary epithelial cell line KIM-2, together with mice exhibiting
      mammary epithelial cell-specific deletion of Stat3 during lactation, we
      demonstrate that expression of mCLCA1 and mCLCA2 is elevated in concert with
      activation of Stat3. By contrast, murine CLCA5 (mCLCA5), the murine orthologue of
      human CLCA2, is significantly upregulated at 24, 72 and 96 h of involution in
      Stat3 knockout mice, suggesting a reciprocal regulation of these proteins by
      Stat3 in vivo. Interestingly, orthotopic tumours arising from transplantation of
      4T1 murine mammary tumour cells exhibit both phosphorylated Stat3 and mCLCA5
      expression. However, we demonstrate that expression is highly compartmentalized
      to distinct subpopulations of cells, and that Stat3 retains a suppressive effect
      on mCLCA5 expression in 4T1 tumour cells. These findings enhance our
      understanding of the regulation of CLCA channel expression both in vitro and in
      vivo, and in particular, demonstrate that expression of mCLCA1 and mCLCA2 during
      involution is profoundly dependent upon Stat3, whereas the relationship between
      mCLCA5 and Stat3 activity is reciprocal and restricted to different
      subpopulations of cells.

PMID- 27711073
TI  - Genetic modifiers of CHEK2*1100delC-associated breast cancer risk.
AB  - PURPOSE: CHEK2*1100delC is a founder variant in European populations that confers
      a two- to threefold increased risk of breast cancer (BC). Epidemiologic and
      family studies have suggested that the risk associated with CHEK2*1100delC is
      modified by other genetic factors in a multiplicative fashion. We have
      investigated this empirically using data from the Breast Cancer Association
      Consortium (BCAC). METHODS: Using genotype data from 39,139 (624 1100delC
      carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we
      analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in
      terms of a polygenic risk score (PRS) and pairwise interaction. RESULTS: The PRS
      conferred odds ratios (OR) of 1.59 (95% CI: 1.21-2.09) per standard deviation for
      BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence
      of deviation from the multiplicative model was found. The OR for the highest
      quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing
      them in the high risk category according to UK NICE guidelines. The OR for the
      lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the
      population average. CONCLUSION: Our results confirm the multiplicative nature of
      risk effects conferred by CHEK2*1100delC and the common susceptibility variants.
      Furthermore, the PRS could identify carriers at a high lifetime risk for clinical
      actions.Genet Med advance online publication 06 October 2016.

PMID- 27711076
TI  - Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a
      pathway that involves redox-responsive genes.
AB  - Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live
      births) characterized by craniofacial defects, including hypoplasia of facial
      bones, cleft palate and palpebral fissures. Over 90% of the cases are due to
      mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here
      we report a novel TCS-like zebrafish model displaying features that fully
      recapitulate the spectrum of craniofacial abnormalities observed in patients. As
      it was reported for a Tcof1+/- mouse model, Treacle depletion in zebrafish caused
      reduced rRNA transcription, stabilization of Tp53 and increased cell death in the
      cephalic region. An increase of ROS along with the overexpression of redox
      responsive genes was detected; furthermore, treatment with antioxidants
      ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae.
      On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp,
      a protein required for proper craniofacial development. Tcof1 knockdown in
      transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial
      cartilage development, reinforcing the notion that Cnbp has a role in the
      pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose
      dependent manner by a ROS-cytoprotective action that prevented the redox
      responsive genes' upregulation but did not normalize the synthesis of rRNAs.
      Finally, a positive correlation between the expression of CNBP and TCOF1 in
      mesenchymal cells from both control and TCS subjects was found. Based on this, we
      suggest CNBP as an additional target for new alternative therapeutic treatments
      to reduce craniofacial defects not only in TCS but also in other
      neurocristopathies.

PMID- 27711077
TI  - RelB/NF-kappaB links cell cycle transition and apoptosis to endometrioid
      adenocarcinoma tumorigenesis.
AB  - Dysfunction of nuclear factor-kappaB (NF-kappaB) signaling has been causally
      associated with numerous human malignancies. Although the NF-kappaB family of
      genes has been implicated in endometrial carcinogenesis, information regarding
      the involvement of central regulators of NF-kappaB signaling in human endometrial
      cancer (EC) is limited. Here, we investigated the specific roles of canonical and
      noncanonical NF-kappaB signaling in endometrial tumorigenesis. We found that NF
      kappaB RelB protein, but not RelA, displayed high expression in EC samples and
      cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC).
      Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c
      Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle
      transition, apoptosis and proliferation in EEC. In contrast, p27 expression was
      enhanced by RelB depletion. Thus, increased RelB in human EC is associated with
      enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results
      reveal that regulatory RelB in noncanonical NF-kappaB signaling may serve as a
      therapeutic target to block EC initiation.

PMID- 27711078
TI  - Attenuated DNA damage repair delays therapy-related myeloid neoplasms in a mouse
      model.
AB  - Therapy-related cancers are potentially fatal late life complications for
      patients who received radio- or chemotherapy. So far, the mouse model showing
      reduction or delay of these diseases has not been described. We found that the
      disruption of Aplf in mice moderately attenuated DNA damage repair and,
      unexpectedly, impeded myeloid neoplasms after exposure to ionizing radiation
      (IR). Irradiated mutant mice showed higher rates of p53-dependent cell death,
      fewer chromosomal translocations, and a delay in malignancy-induced mortality.
      Simultaneous deficiency of p53 abrogated IR-induced apoptosis and the benefit of
      impaired DNA repair on mortality in irradiated Aplf-/- mice. Depletion of APLF in
      non-tumorigenic human cells also markedly reduced the risk of radiation-induced
      chromosomal aberrations. We therefore conclude that proficient DNA damage repair
      may promote chromosomal aberrations in normal tissues after irradiation and
      induce malignant evolution, thus illustrating the potential benefit in
      sensitizing p53 function by manipulating DNA repair efficiency in cancer patients
      undergoing genotoxic therapies.

PMID- 27711079
TI  - Inactivation of Sirt1 in mouse livers protects against endotoxemic liver injury
      by acetylating and activating NF-kappaB.
AB  - Sirtuin 1 (Sirt1) is a deacetylase that regulates many cellular processes in the
      liver, and so far its role in endotoxemic liver injury is elusive. So we
      conditionally inactivate Sirt1 in murine hepatocytes to determine its role in d
      galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver damage, which is a
      well-established experimental model mimicking septic liver injury and fulminant
      hepatitis. Ablation of Sirt1 shows remarkable protection against GalN/LPS-induced
      liver injury, which is a result of enhanced NF-kappaB response because knockdown
      of RelA/p65 negates the protective effect of Sirt1 knockout. Mechanistically, NF
      kappaB p65 is maintained in a hyperacetylated, DNA-binding competent state in
      tumor necrosis factor-alpha (TNF-alpha)-challenged albumin-Cre+ (AlbCre+)
      hepatocytes. Transfection of hepatocytes with a recombinant acetylated p65
      expression construct replicates the protection afforded by Sirt1 knockout.
      Transfection of AlbCre+ hepatocytes with a recombinant wild-type Sirt1 construct,
      rather than a deacetylase-defective one, compromises NF-kappaB activation and
      resensitizes hepatocytes to TNF-alpha-induced apoptosis. Taken together, our
      results demonstrate that Sirt1 deacetylates p65 and compromises NF-kappaB
      activity in hepatocytes when confronted with LPS/TNF-alpha stimulation, leading
      to increased susceptibility to endotoxemic injury. These findings identify a
      possible protein effector to maneuver the hepatic NF-kappaB signaling pathway
      under inflammatory circumstances and a feasible way to increase hepatocellular
      resistance to endotoxin/TNF-alpha toxicity.

PMID- 27711082
TI  - Delayed triggering of oestrogen induced apoptosis that contrasts with rapid
      paclitaxel-induced breast cancer cell death.

PMID- 27711080
TI  - Adeno-associated virus-mediated CASQ2 delivery rescues phenotypic alterations in
      a patient-specific model of recessive catecholaminergic polymorphic ventricular
      tachycardia.
AB  - Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly
      lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin
      2 (CASQ2) gene. We have previously demonstrated that viral transfer of the wild
      type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induced
      mouse model of the disease homozygous carrier of the R33Q mutation. In the
      present study, we investigated the efficacy of the virally mediated gene therapy
      in cardiomyocytes (CMs) differentiated from induced pluripotent stem cells
      (iPSCs) obtained from a patient carrying the homozygous CASQ2-G112+5X mutation.
      To this end, we infected cells with an Adeno-Associated Viral vector serotype 9
      (AAV9) encoding the human CASQ2 gene (AAV9-hCASQ2). Administration of the human
      WT CASQ2 gene was capable and sufficient to restore the physiological expression
      of calsequestrin-2 protein and to rescue functional defects of the patient
      specific iPSC-derived CMs. Indeed, after viral gene transfer, we observed a
      remarkable decrease in the percentage of delayed afterdepolarizations (DADs)
      developed by the diseased CMs upon adrenergic stimulation, the calcium transient
      amplitude was re-established and the density and duration of calcium sparks were
      normalized. We therefore demonstrate the efficacy of the AAV9-mediated gene
      replacement therapy for CPVT2 in a human cardiac-specific model system,
      supporting the view that the gene-therapy tested is curative in models with
      different human mutations of CPVT.

PMID- 27711081
TI  - Hypoxia-induced expression of cellular prion protein improves the therapeutic
      potential of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are 'adult' multipotent cells that promote
      regeneration of injured tissues in vivo. However, differences in oxygenation
      levels between normoxic culture conditions (21% oxygen) and both the MSC niche (2
      8% oxygen) and ischemic injury-induced oxidative stress conditions in vivo have
      resulted in low efficacy of MSC therapies in both pre-clinical and clinical
      studies. To address this issue, we examined the effectiveness of hypoxia
      preconditioning (2% oxygen) for enhancing the bioactivity and tissue-regenerative
      potential of adipose-derived MSCs. Hypoxia preconditioning enhanced the
      proliferative potential of MSCs by promoting the expression of normal cellular
      prion protein (PrPC). In particular, hypoxia preconditioning-mediated MSC
      proliferation was regulated by PrPC-dependent JAK2 and STAT3 activation. In
      addition, hypoxia preconditioning-induced PrPC regulated superoxide dismutase and
      catalase activity, and inhibited oxidative stress-induced apoptosis via
      inactivation of cleaved caspase-3. In a murine hindlimb ischemia model, hypoxia
      preconditioning enhanced the survival and proliferation of transplanted MSCs,
      ultimately resulting in improved functional recovery of the ischemic tissue,
      including the ratio of blood flow perfusion, limb salvage, and
      neovascularization. These results suggest that Hypo-MSC offer a therapeutic
      strategy for accelerated neovasculogenesis in ischemic diseases, and that PrPC
      comprises a potential target for MSC-based therapies.

PMID- 27711084
TI  - HE4 is a novel tissue marker for therapy response and progestin resistance in
      medium- and low-risk endometrial hyperplasia.

PMID- 27711083
TI  - RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain
      metastases - results and lessons learnt.
AB  - BACKGROUND: Brain metastases occur in up to 75% of patients with advanced
      melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited
      effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor
      receptor, epidermal growth factor receptor and rearranged during transfection
      tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared
      WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain
      metastases. METHODS: In this double-blind, multi-centre, phase 2 trial patients
      with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10
      fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo.
      The primary endpoint was progression-free survival in brain (PFS brain). The main
      study was preceded by a safety run-in phase to confirm tolerability of the
      combination. A post-hoc analysis and literature review considered barriers to
      recruiting patients with melanoma brain metastases to clinical trials. RESULTS:
      Twenty-four patients were recruited, six to the safety phase and 18 to the
      randomised phase. The study closed early due to poor recruitment. Median PFS
      brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib
      group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median
      overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI:
      0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue,
      alopecia, confusion and nausea. The most common barrier to study recruitment was
      availability of alternative treatments. CONCLUSIONS: The combination of WBRT plus
      vandetanib was well tolerated. Compared with WBRT alone, there was no significant
      improvement in PFS brain or OS, although we are unable to provide a definitive
      result due to poor accrual. A review of barriers to trial accrual identified
      several factors that affect study recruitment in this difficult disease area.

PMID- 27711086
TI  - Fournier's gangrene. A clinical review.
AB  - INTRODUCTION AND HYPOTHESIS: Fournier's gangrene is a rare, necrotising fasciitis
      of the external genitalia, perineal or perianal regions. The disease has a higher
      incidence in males and risk factors for development include diabetes, HIV,
      alcoholism and other immune-compromised states. The aggressive disease process is
      associated with a high mortality rate of 20-30%. In addition, the increasing age
      and prevalence of diabetes in the population, begs the need for increased
      clinical awareness of Fournier's gangrene with emphasis on early diagnosis and
      management. This review aims to highlight the relevant research surrounding
      Fournier's gangrene, in particular the various prognostic indicators and
      management strategies. METHODS: A search was conducted on the MEDLINE database
      for all applicable research; clinical reviews, retrospective studies and case
      reports. In addition to which a search of the European Association of Urology,
      the British Association for Urological Surgeons and the British Medical Journal
      was conducted for the most recent recommendations. RESULTS: Immediate broad
      spectrum antibiotic therapy and urgent surgical debridement are the core
      managerial principles of Fournier's gangrene. The use of adjunctive therapies
      such as hyperbaric oxygen and vacuum assisted closure are supported in some
      aspects of the literature and disputed in others. The lack of randomized
      controlled studies limits the use of these potential additional therapies to
      patients unresponsive to conventional management. The value of unprocessed honey
      as a topical antimicrobial agent has been highlighted in the literature for small
      lesions in uncomplicated patients. CONCLUSION: Fournier's gangrene is a
      urological emergency with a high mortality rate despite advances in the medical
      and surgical fields. The aggressive nature of the infection advocates the need
      for early recognition allowing immediate surgical intervention. The opposing
      results of available research as well as the lack of high quality evidence
      surrounding emergent therapies prevents their routine use in the management of
      Fournier's gangrene. The absence of a specific care pathway may hinder efficient
      management of Fournier's gangrene, thus based on current guidelines a management
      pathway is suggested.

PMID- 27711085
TI  - Cessation of targeted therapy after a complete response in BRAF-mutant advanced
      melanoma: a case series.
AB  - BACKGROUND: It is unknown whether melanoma patients achieving complete response
      (CR) with targeted therapy can safely discontinue treatment. METHODS: All
      patients treated with BRAF/MEK inhibitors achieving CR and ceasing treatment
      before progression were identified. Clinical data at treatment initiation,
      cessation and progression were examined. RESULTS: A total of 12 eligible patients
      were identified, with median follow-up of 16 months, of whom 6 (50%) recurred at
      a median of 6.6 months after treatment cessation. One patient lost to follow-up
      until presentation with symptomatic recurrence was the only relapser to die. At
      relapse, the remaining five patients had an LDH <1.2 times ULN, four were ECOG 0
      and one ECOG 1. Baseline characteristics and time to CR and to discontinuation
      did not influence the rate of relapse. CONCLUSIONS: A large proportion of
      patients achieving CR with BRAF/MEK inhibitors relapse after treatment cessation.
      The optimal treatment duration in such patients is unclear, particularly where
      alternative treatments are available.

PMID- 27711087
TI  - Chronic obstructive pulmonary disease (COPD) and erectile dysfunction (ED):
      Results of the BRED observational study.
AB  - Most patients with chronic obstructive pulmonary disease (COPD) share many risk
      factors and similar aetiological agents with erectile dysfunction (ED). Both
      conditions also cause serious interference with quality of life and sexual
      relationships. In general, ageing and chronic illness decrease sexual interest,
      sexual function, and testosterone levels. This observational study included 66
      male patients referred to our centre with different grades of COPD. We studied
      the different correlations between COPD and ED. The data collected from each
      patient regarded the following features: demographic and social condition;
      smoking status; clinical status; spirometric measurements. In this group, COPD
      was diagnosed in 78.8% and ED was present in 83.3% with increased severity in
      presence of LUTS and nicotinism.

PMID- 27711088
TI  - A combination of tryptophan, Satureja montana, Tribulus terrestris, Phyllanthus
      emblica extracts is able to improve sexual quality of life in patient with
      premature ejaculation.
AB  - OBJECTIVE: The management of patient affected by premature ejaculation (PE) is
      nowadays not highly satisfactory. Here, we aimed to evaluate the tolerability and
      efficacy of a combination of tryptophan, Satureja montana, Tribulus terrestris,
      Phyllanthus emblica extracts in order to improve sexual quality of life in
      patients with premature ejaculation. MATERIALS AND METHODS: All patients
      attending to 5 urological centers from January 2015 to March 2015, due to
      premature ejaculation were enrolled in this study. At the enrolment visit, all
      subjects underwent self-administered IIEF-5, Male Sexual Health Questionnaire
      Ejaculation Disorder (MSHQEjD), PEDT and IELTS (calculated as mean from that
      perceived by partner and that perceived by patient) and underwent urological
      visit and laboratory examinations. All patients received one tablet per day of a
      combination of tryptophan, Satureja montana, Tribulus terrestris, Phyllanthus
      emblica extracts for 3 months (Group A). After 3 months all patients underwent
      follow-up visit with the same investigations that have been carried out in the
      enrolment visit. The results were compared with a cohort of patients enrolled in
      the same period in another urological center and considered as a control group
      (Group B). All patients in the control group underwent counseling and sexual
      behavioral treatment without any pharmacological compound. RESULTS: At the follow
      up analysis, significant changes in terms of IELT in the Group A (mean
      difference: 31.90; p < 0.05) at 3 months and versus Group B at the intergroup
      analysis (mean difference: 30.30; p < 0.05) were reported. In the group A,
      significant differences from baseline to last follow- up were observed relative
      to IIEF-5 (mean difference: 1.04; p < 0.05), PEDT (mean difference: -2.57; p <
      0.05) and FSH (mean difference: -16.46; p < 0.05). CONCLUSION: In conclusion,
      patients affected by PE may significantly benefit from oral therapy with a
      combination of tryptophan, Satureja montana, Tribulus terrestris, Phyllanthus
      emblica extracts in terms of IELT and PEDT scores improvement.

PMID- 27711089
TI  - Serenoa repens associated with selenium and lycopene extract and bromelain and
      methylsulfonylmethane extract are able to improve the efficacy of levofloxacin in
      chronic bacterial prostatitis patients.
AB  - OBJECTIVE: To date, the management of patients with chronic bacterial prostatitis
      (CBP) is not satisfactory, especially in terms of symptoms relief. Here, we
      evaluated the efficacy and the safety of a combination of serenoa repens,
      selenium and lycopene extract + bromelain and methylsulfonylmethane extract
      associated with levofloxacin in patients with CBP. MATERIALS AND METHODS: All
      patients with clinical and instrumental diagnosis of CBP, admitted to a single
      Urological Institution from March to June 2015 were enrolled in this phase III
      study. All enrolled patients were randomized into two groups: Group A received
      levofloxacin 500 mg o.d. for 14 days associated with lycopene and
      methylsulfonylmethane; Group B received levofloxacin (500 mg o.d. for 14 days)
      only. Clinical and microbiological analyses were carried out at the time of
      admission (T0) and during the followups at 1 month (T1) and 6 months (T2) from
      the end of the treatment. NIH Chronic Prostatitis Symptom Index (CPSI),
      International Prostatic Symptom Score (IPSS) and Quality of Well-Being (QoL)
      questionnaires were used. The main outcome measures were the rate of
      microbiological cure and the improvement in questionnaire results from baseline
      at the end of the follow-ups period. RESULTS: Forty patients were enrolled in
      Group A and 39 in Group B. During the follow-up (T1), we recorded a significant
      changes in terms of NIH-CPSI and IPSS in Group A (mean difference: 17.6 +/- 2.65;
      12.2 +/- 2.33; p < 0.01; p < 0.05, respectively) and versus Group B at the
      intergroup analysis (mean difference: -9 +/- 1.82; -8.33 +/- 1.71; p < 0.05; p <
      0.05, respectively). No differences were reported in terms of microbiological
      findings between the two groups. At the second follow-up visit (T2),
      questionnaire results demonstrated statistically significant differences between
      groups (p < 0.001). One patient in Group A (2.5%) and 7 patients (17.9%) in Group
      B showed a symptomatic and microbiological recurrence (p = 0.02). CONCLUSIONS:
      The combination of serenoa repens, selenium, lycopene + bromelain and
      methylsulfonylmethane extracts improved the clinical efficacy of levofloxacin in
      patients affected by CBP without the development of side effects.

PMID- 27711090
TI  - Penile vascular diagnostic categorization using penile duplex Doppler ultrasound:
      Differences in vascular hemodynamics parameters by differences in anatomic
      sampling location.
AB  - OBJECTIVES: In 2013 the International Society for Sexual Medicine(ISSM) published
      the guidelines regarding the standard operating procedure (SOP) for penile duplex
      Doppler ultrasound (PDDU). Although ISSM-SOP have given important strides in
      reducing interobserver variability in PDDU by procedural protocol and parameters
      these guidelines do not address the anatomic location along the penis at which
      hemodynamic measurements have to be done. In our opinion a "double sampling" may
      be interesting to detect the arteriogenic or venogenic nature of the erectile
      dysfunction (ED). In particular sampling measurements at the "crus" (at the level
      of the peno-scrotal junction) may be significative for detection of veno
      occlusive dysfunction (VOD),whereas an evaluation at "mid penis" (1/2 distance
      between peno-scrotal junction and coronal sulcus), may be useful to diagnose an
      arterial insufficiency (AI). MATERIAL AND METHODS: We evalued 90 men, mean age
      56.3, affected with ED of medium degree, responder to PDE5-I that urdergone to
      PDDU and also responder after pharmacologic intracavernosal injection (PII)of
      prostaglandin E1 20 mcg, with rigid erection and normal maintenance. We moreover
      evalued 90 men in youthful age (mean 35.2), in absence of vascular risk factors,
      no responder to PDE5-I that undergone to PDDU by PII at high dosage (bimix:
      prostaglandin E1 20 mcg, papaverine 20 mg). RESULTS: In the first pool the
      sampling at "mid penis" resulted significative for arterial insuffciency (AI) in
      81% (73), in presence of normal or borderline end diastolic velocity (EDV).
      Sampling at the "crus" resulted negative for VOD in 90% (81). In the second pool,
      66.6% (60) resulted responder with rigid erection and normal maintenance in
      presence of normal hemodynamic parameters: peak systolic velocity (PSV) and end
      diastolic velocity (EDV) both at the "crus" and at "mid penis" sampling. 33.4%
      (30) responded with a semirigid erection and manifested a constant deficit of
      maintenance; at the "crus"and at "mid penis" the hemodynamic arterial parameters
      resulted normal. At the "crus" the EDV resulted significantly augmented (VOD
      index) in 96.6% (29); at "mid penis" augmented EDV was founded in 50% (15).
      CONCLUSIONS: These observational data would be able to confirm the utility of a
      routinary "double sampling" procedure, at the "crus" and at "md penis", during
      PDDU in order to better distinguish between VOD or AI or in any case to be useful
      to stimulate a future more precise standardization in execution of PDDU
      examination.

PMID- 27711091
TI  - Testicular prosthesis: Patient satisfaction and sexual dysfunctions in testis
      cancer survivors.
AB  - PURPOSE: We studied patient satisfaction about sexual activity after prosthesis
      implantation using validated questionnaires with the aim to discover if
      testicular prosthesis could be responsible of sexual dysfunctions (erectile
      dysfunction or premature ejaculation). MATERIALS AND METHODS: We evaluated a
      total of 67 men who underwent radical orchiectomy for testicular cancer and a
      silicon testicular prosthesis implantation from January 2008 to June 2014 at our
      Hospital. These patients completed 5 validated questionnaires the day before
      orchiectomy and 6 months after surgery: the International Index of Erectile
      Function 5 (IIEF5), the Premature Ejaculation Diagnostic Tool (PEDT), the Body
      Exposure during Sexual Activities Questionnaire (BESAQ), the Body-Esteem Scale
      and the Rosenberg Self- Esteem Scale. We also evaluated 6 months after surgery
      any defects of the prosthesis complained by the patients. RESULTS: The
      questionnaires completed by patients didn't show statistically significant
      changes for erectile dysfunction (p > 0.05) and premature ejaculation (p > 0.05).
      On the contrary the psychological questionnaires showed statistically significant
      change for the BESAQ (p < 0.001) and the Body Esteem Scale (p < 0.001), but not
      for the Rosenberg Self-Esteem Scale (p > 0,05). A total of 15 patients (22.37%)
      were dissatisfied about the prosthesis: the most frequent complaint (8 patients;
      11.94%) was that the prosthesis was firmer than the normal testis. CONCLUSIONS:
      Testicular prosthesis implantation is a safe surgical procedure that should be
      always proposed before orchiectomy for cancer of the testis. The defects
      complained by patients with testicular prosthesis are few, they don't influence
      sexual activity and they aren't able to cause erectile dysfunction or premature
      ejaculation.

PMID- 27711092
TI  - Explorative surgery for acute scrotal pain: The importance of patient age, side
      affected, time to surgery and surgeon.
AB  - INTRODUCTION AND OBJECTIVE: Testicular torsion must be diagnosed quickly and
      accurately. The delay of the diagnosis and the subsequent delay of surgery may
      lead to loss testicular viability and orchidectomy. Aim of our retrospective
      evaluation was to define which element should be considered as major support to
      the clinician in distinguishing spermatic cord torsion from the other diseases
      mimicking this clinical emergency requiring surgical exploration. MATERIAL AND
      METHODS: We retrospectively reviewed all clinical and instrumental data of
      emergency scrotal exploration performed for acute scrotal pain at two different
      Urological Department in a 10 year period. Results of surgical exploration
      represented the four diagnostic categories in which patients were divided for
      statistical evaluation. We evaluated the relationship between diagnosis performed
      by testicular surgical exploration and the all clinical data available including
      surgeon involved in the procedures. RESULTS: A total of 220 explorative scrotal
      surgery were considered. We divided the cases in 4 categories according to the
      diagnostic results of each surgical procedure. Of all, spermatic cord torsion was
      diagnosed in 45% (99/220). The total testis salvage rate was of 78.8%. The
      patients with a diagnosis of spermatic cord torsion were older than patients with
      appendix torsion (15 vs 11 years in mean). When the affected side was the left,
      the probability to have a diagnosis of spermatic cord torsion was higher than the
      right side [chi2 (2, N = 218) = 11.77, p < 0.01]. Time elapsing between onset of
      symptoms and testicular salvagewas significantly lower even than in case of
      appendix torsion/necrosis (p < .0001), and of others pathologies diagnosed (p =
      .0383). CONCLUSION: In case of spermatic cord torsion, in addition to the
      clinical data, patient age and left side affected may represent an independent
      diagnostic predicting factor. The time elapsing between onset of symptoms and
      explorative surgery remain the only still prognostic factor for testicular
      viability.

PMID- 27711093
TI  - In the search of novel urine biomarkers for the early diagnosis of prostate
      cancer. Intracellular or secreted proteins as the target group? Where and how to
      search for possible biomarkers useful in the everyday clinical practice.
AB  - OBJECTIVE: To search which category of proteins can be detected in urine in order
      to examine subsequently its ability to improve our accuracy for the diagnosis of
      Prostate Cancer (PCa) as biomarkers in clinical useful fluids like urine and
      serum. Material and method(s): Urine samples of 127 patients were obtained after
      a vigorous transrectal prostatic massage to both lobes. The patients were
      considered to have a high risk for PCa according to their PSA (> 4 ng/ml), their
      digital rectal examination (DRE) (positive for suspicious prostatic lesions) or
      to their abnormal PSA kinetics (PSA velocity (PSAV > 0.75 ng/mL). All patients
      subsequently were subjected to an extended 10-core per prostatic lobe TRUS-b
      (total 20 prostatic samples). The proteins that were chosen to be detected in the
      urine samples with Western-blot, as possible biomarkers, were Glutathione
      peroxidase 3 precursor (GPx3), Cofilin-1 (CFL1), Heat shock protein-90beta (HSP
      90beta), Zinc alpha 2-glycoprotein (ZAG) and secreted protein acidic and rich in
      cysteine (SPARC).These proteins have been detected previously in the prostatic
      tissue by proteomics proving their discriminative ability between patients with
      prostate cancer and benign prostatic hyperplasia. RESULT(S): From the five
      proteins, only the secreted Zinc alpha 2-glycoprotein was detected in urine
      showing a promising ability in the improvement of our diagnostic accuracy for the
      early diagnosis of prostate cancer. CONCLUSIONS: From various categories of
      proteins that have already been detected in the tissue of prostate by proteomics,
      only secreted protein Zinc alpha 2-glycoprotein showed a clear signal in the
      urine, proving its discriminative potential for the early diagnosis of PCa.

PMID- 27711094
TI  - Emergency management of ureteral stones: Evaluation of two different approaches
      with an emphasis on patients' life quality.
AB  - OBJECTIVES: To evaluate the emergency management of obstructing ureteral calculi
      with two different techniques (SWL and URS) with an emphasis on patients life
      quality. METHODS: A total of 80 patients presenting with acute colic pain due to
      a single obstructing ureteral stone were treated within 24 hours following the
      onset of pain with two different approaches in a randomized manner. Patients
      requiring DJ stent placement and/or auxiliary measures after both procedures were
      excluded and the remaining 65 patients were evaluated [Group1: ESWL (n = 34);
      Group 2: URS (n = 31)]. Patients were followed during 4-weeks period with respect
      to the analgesic requirement, number of renal colic attacks and emergency
      department visits along with the HRQOL scores. RESULTS: While 26 patients treated
      with URS (83.9%) were stone-free, 24 cases in SWL were stone-free (70.6%) after 4
      weeks. Evaluation of the cases during this follow-up period demonstrated that
      cases undergoing SWL required significantly higher amount of analgesics when
      compared with URS group (p < 0.001). In addition to the lower mean number of
      renal colic attacks and emergency department visits in URS group; both the mean
      HRQOL in terms of EQ-5D index and mean EQ-5D VAS values were also significantly
      higher in these cases when compared with the cases tretaed with SWL. CONCLUSIONS:
      Due to the negative impact of stone related events after emergency SWL on
      patients HRQOL, emergency URS may be applied more effectively with the advantages
      of prompt fragmentation of the calculi along with the immediate relief of
      obstruction and pain.

PMID- 27711095
TI  - Metabolic evaluation in patients with infected nephrolithiasis: Is it necessary?
AB  - Fifty-four patients with infected renal lithiasis underwent complete metabolic
      evaluation searching for underlying factors contributing to stone formation
      including urine analysis and culture. Metabolic abnormalities were significantly
      more present in patients with mixed infected stones (struvite+/-apatite and
      calcium oxalate) than in patients with pure infected stones (struvite+/-carbonate
      apatite): hypercalciuria in 40%, hyperoxaluria in 34% and hyperuricosuria in 28%
      (p < 0.05). Urinary excretion of citrate was low in both groups without
      statistically significant difference (238+/-117 mg/24 h vs 214+/-104 mg/24/h, t =
      0.72, p = 0.5). The few metabolic abnormalities present in patients with pure
      infected stones should suggest that urinary tract infection could change the
      urine chemistry in a lithogenic direction and be only cause of stone formation.

PMID- 27711096
TI  - Retrograde intrarenal surgery (RIRS), regular and small sized percutaneous
      nephrolithotomy (PCNL) in daily practice: European Association of Urology Section
      of Urolithiasis (EULIS) Survey.
AB  - OBJECTIVE: A wide selection of both anterograde and retrograde mini-invasive
      procedures exist for stones' treatment. The 2016 European Association of Urology
      (EAU) guidelines still don't univocally define a best option. Our purpose is to
      give an overview on some European Stone Centers' customs and to compare real life
      clinical practice with statements of opinion leaders and Guidelines. MATERIALS
      AND METHODS: In 2015 we performed a survey in 3 step about the spread of
      retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL)
      techniques among EAU Section of Urolithiasis (EULIS) members. The 1st and 2nd
      steps dealt with the definition of EULIS urologist and department by collecting
      personal opinions about the endoscopic techniques. The third step was about
      clinical results. This paper presents data from the first two steps. RESULTS:
      Ninety-one people answered. Out of them, 80% are European and 42% work in Centres
      fully dedicated to stone treatment. In particular, 50% of responders perform more
      than 80 RIRS/year, 25% more than 80 PCNL/year, 48% more than 100 extracorporeal
      shock wave lithotripsy (SWL)/year. RIRS is mainly used to treat stones < 2 cm
      both as primary treatment and after SWL failure. 73% don't perform routine pre
      stenting and 66% ordinarily use a ureteral sheath. Hospital stay for RIRS is 24h
      for 70% of responders. Regular PCNL is performed by 87% of the responders,
      MiniPCNL by 58%, Ultra-MiniPCNL by 23% and MicroPCNL by 28%. Pneumatic balloon
      dilation is the favourite dilation technique (49%). 37% of responders perform
      PCNL always in the supine position, 21% always in the prone one. Almost all the
      responders agree about using Mini, Ultra-Mini and MicroPCNL for 1-2 cm stones.
      Approximately 50% also use MiniPCNL for stones > 2 cm. CONCLUSION: our survey
      confirms the great heterogeneity existing in stones' treatment techniques in
      daily practice.

PMID- 27711097
TI  - Chylous ascites as a complication of left sided robot-assisted laparoscopic
      partial nephrectomy.
AB  - OBJECTIVE: The aim of the study was to present a case series of the sparsely
      reported complication of chylous ascites (CA) after left sided robot-assisted
      laparoscopic partial nephrectomy (RALPN), identify possible risk factors for the
      development of postoperative CA, and explore current recommendations for
      identification, management and prevention of CA. MATERIAL AND METHODS: A
      retrospective review of patients that were treated with a RALPN during a one year
      time period (August 2012 to August 2013) by one surgeon at our institution was
      conducted. A total of 12 patients were included in the study. Demographics, tumor
      characteristics, and perioperative outcomes were assessed. RESULTS: Three
      patients in the study experienced postoperative CA. All three patients had left
      sided surgery. The initial clinical suspicion for CA was raised due to complaints
      of abdominal pain with increased milky appearance of JP fluid. JP triglycerides
      were elevated in all three patients. The patients responded to conservative
      measures, with two patients treated with medium chain triglyceride diets and one
      patient treated with total parenteral nutrition (TPN). Among the patients treated
      with RALPN, the group that was diagnosed with postoperative CA (CA group) was
      found to have a statistically significant lower average body mass index (BMI) as
      compared to the group that did not have CA (non-CA group) (24.67 kg/m2 in the CA
      group versus 31.77 kg/m2 in the non-CA group; P = 0.026). Other demographic data,
      tumor characteristics, and perioperative outcomes were similar in both groups.
      CONCLUSIONS: CA as a result of RALPN is a newly reported and rare postoperative
      complication. As utilization of RALPN continues to increase, urologists should be
      aware of this possible complication and be adept at diagnosing and managing CA.
      We suggest that left sided retroperitoneal surgery and a lower BMI preoperatively
      be considered risk factors for developing this complication.

PMID- 27711098
TI  - Bleeding during laparoscopic partial nephrectomy: Can a hemostatic matrix help to
      improve hemostasis?
AB  - OBJECTIVES: To evaluate the possible role of an hemostatic matrix on hemostasis,
      perioperative outcomes and complications in patients who underwent laparoscopic
      partial nephrectomy (LPN). MATERIALS AND METHODS: Patients charts were analyzed
      retrospectively and their demographic characteristics, operative parameters and
      follow-up results were recorded. Patients were divided into two groups, according
      to those who used an hemostatic matrix as Group 1 (n = 41) and those who did not
      used as Group 2 (n = 44). Demographic characteristics of patients, tumor
      features, operation time, clamping of the renal vessels, ischemia time, suturing
      of the collecting system, perioperative hemorrhage and complications were
      evaluated. Histopathological results, surgical margin status, creatinine level
      and recurrence at the 3rd month of follow up were analyzed. Statistical analyses
      were performed with SPSS 17.0 and significance was set at p value of < 0.05.
      RESULTS: The mean RENAL nephrometry score was 5.9 +/- 2.0 and the mean tumor size
      was 35 +/- 12 mm. All patients had a single tumor and 44 of them had a tumor in
      the right kidney. The renal artery was clamped in 79 cases and the mean ischemia
      time was 20.1 +/- 7 minutes. The mean tumor size and the mean RENAL nephrometry
      score was statistically higher in Group 1 (p: 0.016 and p < 0.001, respectively).
      Pelvicaliceal repair was more common in Group 1 due to deeper extension of tumors
      in this group (p: 0.038). In Group 1, less hemorrhage and blood transfusion
      requirement, with shorter ischemia and operation time was detected. CONCLUSION:
      The outcomes of the recent study showed that adjunctive use of an hemostatic
      matrix improves hemostasis and decreases hemorrhagic complications during LPN.
      Further prospective studies are required to assess the potential role of an
      hemostatic matrix in LPN.

PMID- 27711099
TI  - Telerounding & telementoring for urological procedures.
AB  - Telemedicine is the use of medical information exchanged from one site to another
      via electronic communications to improve a patient's clinical health status.
      Telemedicine includes a growing variety of applications and services using two
      way video, email, smart phones, wireless tools and other forms of
      telecommunications technology. Starting out over forty years ago with
      demonstrations of hospitals extending care to patients in remote areas, the use
      of telemedicine has spread rapidly and is now becoming integrated into the
      ongoing operations of hospitals, specialty departments, home health agencies,
      private physician offices as well as consumer's homes and workplaces. There's
      also a current trend in the use of telemedicine in urology. In the present paper
      we aimed to review the recent literature about telemedicine and the use of
      telerounding and telementoring in urological procedures.

PMID- 27711100
TI  - May ultrasound probe size influence pain perception of needle piercing during
      transrectal prostate biopsy? A prospective evaluation.
AB  - INTRODUCTION AND OBJECTIVE: Transrectal ultrasound guided prostate biopsy (TRUS
      Bx) is the definitive step in the diagnosis of prostate cancer (CaP). Patients
      (pts) generally experience significant pain during the procedure at the point
      that biopsy should be accompanied by some form of anesthesia. Several different
      factors influence pain perception (PP) during TRUS-Bx. In our study we want to
      assess that the use of an ergonomic smaller sized probe reduces PP during the
      procedure independently from the administration of local anesthesia or pain
      relieving drugs. MATERIALS AND METHODS: This was a prospective, randomized study
      in which 114 pts who underwent TRUS-Bx due to abnormal PSA and/or to digital
      rectal examination (DRE) suspicious findings were considered eligible. Pts were
      split in two TRUS-Bx groups into which we used two different sized ultrasound
      probes. In group 1, 61 pts underwent TRUS-Bx with ALOKA end fire probe (size 74
      mm). In group 2, 53 pts underwent TRUS-Bx with B-K Type 8818 probe (size 58 mm).
      Both groups were treated with no local anesthesia or pain relieving drugs. Pain
      was evaluated three times using a 10-point visual analogue scale (VAS), during
      the DRE (VAS 1), during the insertion of the probe (VAS 2) and during the needle
      piercing (VAS 3). RESULTS: Mean age of pts was 68.03 (SD 8.51); mean tPSA and
      mean prostate volume was 7.75 (SD 4.83) and 45.17cc (SD 17.7), respectively. The
      two groups were homogeneous respect to tPSA (p = 0.675) and to prostate volume (p
      = 0.296); age was significantly different (p = 0.04) between Group 1 (65.93) and
      Group 2 (70.43), whereas no statistically significant correlation between VAS 3
      and age was observed (p = 0.179). Analyzing pain perception, we found no
      statistically significant difference between the two groups in DRE (VAS 1; p =
      0.839); on the contrary, patients in Group 1 experienced on average more pain
      than other in Group 2 both during the insertion of the probe (VAS 2 3.49 vs 1.09;
      p < 0.001) and during the needle piercing VAS 3 (2.8 vs 2.00; p < 0.05). The
      discomfort during probe insertion and manipulation was perceived as very high
      (VAS 2 > 5) in 42.6% of patients in Group 1 and in 9.4% in Group 2. Globally, the
      procedure was well tolerated (mean VAS score < 3) in 77% of patients in Group 1
      and in 90% in Group 2. The proportion of patients who experienced more than
      moderate pain (VAS > 5) during needle piercing ranged 24.6 % in Group 1 to 18.9 %
      in Group 2. CONCLUSIONS: Patients who underwent a TRUS-Bx with the 58-mm
      circumference probe were found to experience lower degree of pain not only during
      the insertion of the probe through the anal sphincter, but also in the moment of
      needle piercing.

PMID- 27711101
TI  - Non sex-related subtotal rupture of the corpus cavernosum without urethral
      injury: A case report and literature review.
AB  - Although penile fracture is a rare case, it is a well-described urologic
      emergency. It results from the rupture of the tunica albuginea of corpora
      cavernosa by blunt strain that commonly mandates immediate surgical exploration.
      Urethral injury may also accompany penile fracture. An ideal anamnesis and a
      special physical examination were determinant to achieve a correct diagnosis. It
      is usually diagnosed based on clinical examination, but ultrasonography can be
      very helpful in diagnosis. The treatment is based on the presence of associated
      urethral injury. Early surgery is preferable to conservative management, because
      it is associated with better outcomes and fewer long-term complications. The
      surgical repair of cavernous body can produce good results, with a favorable
      prognosis and minimal rate of complications. We present a penile fracture case of
      34-year-old with subtotal rupture of the right corpus cavernosum without urethral
      injury who treated by early surgery and good results.

PMID- 27711102
TI  - Priapism and glucose-6-phosphate dehydrogenase deficiency: An underestimated
      correlation?
AB  - Priapism is a rare clinical condition characterized by a persistent erection
      unrelated to sexual excitement. Often the etiology is idiopathic. Three cases of
      priapism in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients have
      been described in literature. We present the case of a 39-year-old man with
      glucose- 6-phosphate dehydrogenase deficiency, who reached out to our department
      for the arising of a non-ischemic priapism without arteriolacunar fistula. We
      suggest that the glucose-6-phosphate dehydrogenase deficiency could be an
      underestimated risk factor for priapism.

PMID- 27711103
TI  - Fournier's gangrene: Clinical case and review of the literature.
AB  - Fournier's gangrene is a life-threatening acute necrotizing fasciitis of
      perianal,genitourinary and perineal areas. Nowadays, is well known that Fournier
      gangrene is almost never an idiopathic disease. In this article we report a case
      of a 70-year-old patient that initially was not treated properly. The gold
      standard therapy of the Fournier's gangrene remains today a complete, early and
      extended surgical debridement.

PMID- 27711104
TI  - Ultrasonographic study of subcutaneous penile granuloma secondary to silicone
      injection.
AB  - Penile augmentation has been reported in the literature by injecting various
      materials. This study reports our experience in management of penile augmentation
      complications associated with selfpenile injection of silicone liquid. After a
      careful ultrasound study, the penile skin was excised through a circumferential
      sub-coronal incision and dissected with the silicon mass. Histology was well
      compatible with silicone granulomas. The patient was discharged after 24 hours.
      Ultrasonography has permitted preoperatively to determine if the plane between
      the indurated inflammatory tissue and the Buck's fascia was preserved for the
      complete surgical excision of affected tissue.

PMID- 27711105
TI  - Adenomatous hyperplasia of the rete testis: A rare intrascrotal lesion managed
      with limited testicular excision.
AB  - INTRODUCTION: Testicular cancer is one of the most frequent in young men and its
      incidence is increasing in recent years because of incidental finding during
      routine ultrasound exams. Adenomatous hyperplasia of the rete testis is one of
      the benign and rare pathological types incidentally detected and very few cases
      are described in the literature. CASE REPORT: A 40 years old man come to our
      attention for a balanoposthitis without testicular pain. During andrological
      examination we performed palpation of the testes and we noticed a palpable nodule
      of hard consistency in the left testicle. We then performed an ultrasound exam of
      the testis which highlighted the presence of an intra-didymus neoformation with
      diameters of 1.2 x 1.6 cm and with the presence of cysts inside. We also
      performed blood tests to check tumor markers alpha fetoprotein, beta hCG and LDH
      which resulted inside the normal range. We then conducted a chest and abdomen CT
      scan that showed no pathological elements. Therefore, as we suspected that this
      tumor was benign, we performed an enucleation of the neoplasm. The definitive
      histological examination revealed the presence of dilated ducts lined with
      epithelial cubic-columnar cells with clear cytoplasm rich in glycogen and the
      pathologist so concluded that the tumor could be classified as adenomatous
      hyperplasia of the rete testis. At three months of follow up, the patient doesn't
      have any recurrent lesion to either testicles. DISCUSSION: Adenomatous
      hyperplasia of the rete testis is a very rare intrascrotal lesion. This
      histological type is the most frequent between benign lesion of the ovary, but
      few works in literature reported this histological type in the male gonad and, in
      most of these works, authors described these lesion at epididymis. CONCLUSION: We
      believe that a conservative approach must be considered mandatory in case of
      testicular lesions 1.5 cm in diameter. A radical approach might have alterate
      fertility of the patient and also have caused psychological trauma more than an
      enucleation. However a longer follow up is needed to understand if this was the
      right decision for the oncological point of view.

PMID- 27711106
TI  - A rubber tube in the bladder as a complication of autoerotic stimulation of the
      urethra.
AB  - Self-insertion of foreign bodies in the urethra is most commonly associated with
      sexual or erotic arousal of adolescents with mental health disorders. Rarely it
      may practiced by healthy adults for masturbation. Migration of foreign bodies
      used for the abovementioned purpose from the urethra to adjacent organs is a
      relatively uncommon urologic problem that may cause serious complications which
      arose tardive. Presentation includes a variety of acute or chronic symptoms that
      depend of the underlying complications. The method of extraction depends on the
      shape, size and nature of the object and should be tailored according to the
      condition of the patient. In the present article we present a case of a rubber
      tube inserted to the urethra for erotic arousal purposes which migrated to the
      bladder during masturbation.

PMID- 27711107
TI  - Primary pure carcinoid tumour of the testis: A case report and review of the
      literature.
AB  - Primary testicular carcinoid tumours (TCT) are very rare, and a large tumour size
      and the presence of carcinoid syndrome predict a malignant course.
      Histologically, it is difficult to differentiate between benign and malignant
      TCTs. We report a case of a primary pure TCT with an unusual presentation in a 23
      year-old man, who had an asymptomatic, enlarged scrotum on the right side for 7
      years. On gross examination, the tumour was 9.6 cm in diameter. The Ki-67
      labelling index was 19.8%. High inguinal orchidectomy was performed, and 30
      months after surgery the patient remains asymptomatic.

PMID- 27711108
TI  - Mechanistic Insight into the Host Transcription Inhibition Function of Rift
      Valley Fever Virus NSs and Its Importance in Virulence.
AB  - Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the
      family Bunyaviridae, causes periodic outbreaks in livestocks and humans in
      countries of the African continent and Middle East. RVFV NSs protein, a
      nonstructural protein, is a major virulence factor that exhibits several
      important biological properties. These include suppression of general
      transcription, inhibition of IFN-beta promoter induction and degradation of
      double-stranded RNA-dependent protein kinase R. Although each of these biological
      functions of NSs are considered important for countering the antiviral response
      in the host, the individual contributions of these functions towards RVFV
      virulence remains unclear. To examine this, we generated two RVFV MP-12 strain
      derived mutant viruses. Each carried mutations in NSs that specifically targeted
      its general transcription inhibition function without affecting its ability to
      degrade PKR and inhibit IFN-beta promoter induction, through its interaction with
      Sin3-associated protein 30, a part of the repressor complex at the IFN-beta
      promoter. Using these mutant viruses, we have dissected the transcription
      inhibition function of NSs and examined its importance in RVFV virulence. Both
      NSs mutant viruses exhibited a differentially impaired ability to inhibit host
      transcription when compared with MP-12. It has been reported that NSs suppresses
      general transcription by interfering with the formation of the transcription
      factor IIH complex, through the degradation of the p62 subunit and sequestration
      of the p44 subunit. Our study results lead us to suggest that the ability of NSs
      to induce p62 degradation is the major contributor to its general transcription
      inhibition property, whereas its interaction with p44 may not play a significant
      role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an
      impaired general transcription inhibition function showed a reduced cytotoxicity
      in cell culture and attenuated virulence in young mice, compared with its
      parental virus MP-12, highlighting the contribution of NSs-mediated general
      transcription inhibition towards RVFV virulence.

PMID- 27711109
TI  - Mycetoma Pulmonary Secondaries from a Gluteal Eumycetoma: An Unusual
      Presentation.

PMID- 27711110
TI  - Stoichiometric Representation of Gene-Protein-Reaction Associations Leverages
      Constraint-Based Analysis from Reaction to Gene-Level Phenotype Prediction.
AB  - Genome-scale metabolic reconstructions are currently available for hundreds of
      organisms. Constraint-based modeling enables the analysis of the phenotypic
      landscape of these organisms, predicting the response to genetic and
      environmental perturbations. However, since constraint-based models can only
      describe the metabolic phenotype at the reaction level, understanding the
      mechanistic link between genotype and phenotype is still hampered by the
      complexity of gene-protein-reaction associations. We implement a model
      transformation that enables constraint-based methods to be applied at the gene
      level by explicitly accounting for the individual fluxes of enzymes (and
      subunits) encoded by each gene. We show how this can be applied to different
      kinds of constraint-based analysis: flux distribution prediction, gene
      essentiality analysis, random flux sampling, elementary mode analysis,
      transcriptomics data integration, and rational strain design. In each case we
      demonstrate how this approach can lead to improved phenotype predictions and a
      deeper understanding of the genotype-to-phenotype link. In particular, we show
      that a large fraction of reaction-based designs obtained by current strain design
      methods are not actually feasible, and show how our approach allows using the
      same methods to obtain feasible gene-based designs. We also show, by extensive
      comparison with experimental 13C-flux data, how simple reformulations of
      different simulation methods with gene-wise objective functions result in
      improved prediction accuracy. The model transformation proposed in this work
      enables existing constraint-based methods to be used at the gene level without
      modification. This automatically leverages phenotype analysis from reaction to
      gene level, improving the biological insight that can be obtained from genome
      scale models.

PMID- 27711111
TI  - The Electrophysiology of Basic Phrase Building.
AB  - A defining trait of linguistic competence is the ability to combine elements into
      increasingly complex structures to denote, and to comprehend, a potentially
      infinite number of meanings. Recent magnetoencephalography (MEG) work has
      investigated these processes by comparing the response to nouns in combinatorial
      (blue car) and non-combinatorial (rnsh car) contexts. In the current study we
      extended this paradigm using electroencephalography (EEG) to dissociate the role
      of semantic content from phonological well-formedness (yerl car). We used event
      related potential (ERP) recordings in order to better relate the observed
      neurophysiological correlates of basic combinatorial operations to prior ERP work
      on comprehension. We found that nouns in combinatorial contexts (blue car)
      elicited a greater centro-parietal negativity between 180-400ms, independent of
      the phonological well-formedness of the context word. We discuss the potential
      relationship between this 'combinatorial' effect and classic N400 effects. We
      also report preliminary evidence for an early anterior negative deflection
      immediately preceding the critical noun in combinatorial contexts, which we
      tentatively interpret as an electrophysiological reflex of syntactic structure
      initialization.

PMID- 27711112
TI  - Chromosomal Replication Complexity: A Novel DNA Metrics and Genome Instability
      Factor.
AB  - As the ratio of the copy number of the most replicated to the unreplicated
      regions in the same chromosome, the definition of chromosomal replication
      complexity (CRC) appears to leave little room for variation, being either two
      during S-phase or one otherwise. However, bacteria dividing faster than they
      replicate their chromosome spike CRC to four and even eight. A recent
      experimental inquiry about the limits of CRC in Escherichia coli revealed two
      major reasons to avoid elevating it further: (i) increased chromosomal
      fragmentation and (ii) complications with subsequent double-strand break repair.
      Remarkably, examples of stable elevated CRC in eukaryotic chromosomes are well
      known under various terms like "differential replication," "underreplication,"
      "DNA puffs," "onion-skin replication," or "re-replication" and highlight the
      phenomenon of static replication fork (sRF). To accurately describe the resulting
      "amplification by overinitiation," I propose a new term: "replification"
      (subchromosomal overreplication). In both prokaryotes and eukaryotes,
      replification, via sRF processing, causes double-strand DNA breaks and, with
      their repair elevating chromosomal rearrangements, represents a novel genome
      instability factor. I suggest how static replication bubbles could be stabilized
      and speculate that some tandem duplications represent such persistent static
      bubbles. Moreover, I propose how static replication bubbles could be transformed
      into tandem duplications, double minutes, or inverted triplications. Possible
      experimental tests of these models are discussed.

PMID- 27711113
TI  - MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes
      in Mice.
AB  - miR-155 plays critical roles in numerous physiological and pathological
      processes, however, its function in the regulation of blood glucose homeostasis
      and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal
      that miR-155 levels are downregulated in serum from type 2 diabetes (T2D)
      patients, suggesting that miR-155 might be involved in blood glucose control and
      diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that
      miR-155 has no effects on the pancreatic beta-cell proliferation and function.
      Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia,
      improved glucose tolerance and insulin sensitivity. Conversely, miR-155
      deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin
      resistance. In addition, consistent with a positive regulatory role of miR-155 in
      glucose metabolism, miR-155 positively modulates glucose uptake in all cell types
      examined, while mice overexpressing miR-155 transgene show enhanced glycolysis,
      and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or
      skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at
      least partially, through miR-155-mediated repression of important negative
      regulators (i.e. C/EBPbeta, HDAC4 and SOCS1) of insulin signaling. Taken
      together, these findings demonstrate, for the first time, that miR-155 is a
      positive regulator of insulin sensitivity with potential applications for
      diabetes treatment.

PMID- 27711114
TI  - Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle
      Function.
AB  - OBJECTIVES: Enzyme replacement therapy has shown to be effective for
      childhood/adult onset Pompe disease (AOPD). The discovery of biomarkers useful
      for monitoring disease progression is one of the priority research topics in
      Pompe disease. Muscle MRI could be one possible test but the correlation between
      muscle MRI and muscle strength and function has been only partially addressed so
      far. METHODS: We studied 34 AOPD patients using functional scales (Manual
      Research Council scale, hand held myometry, 6 minutes walking test, timed to up
      and go test, time to climb up and down 4 steps, time to walk 10 meters and Motor
      Function Measure 20 Scale), respiratory tests (Forced Vital Capacity seated and
      lying, Maximun Inspiratory Pressure and Maximum Expiratory Pressure), daily live
      activities scales (Activlim) and quality of life scales (Short Form-36 and
      Individualized Neuromuscular Quality of Life questionnaire). We performed a whole
      body muscle MRI using T1w and 3-point Dixon imaging centered on thighs and lower
      trunk region. RESULTS: T1w whole body muscle MRI showed a homogeneous pattern of
      muscle involvement that could also be found in pre-symptomatic individuals. We
      found a strong correlation between muscle strength, muscle functional scales and
      the degree of muscle fatty replacement in muscle MRI analyzed using T1w and 3
      point Dixon imaging studies. Moreover, muscle MRI detected mild degree of fatty
      replacement in paraspinal muscles in pre-symptomatic patients. CONCLUSION: Based
      on our findings, we consider that muscle MRI correlates with muscle function in
      patients with AOPD and could be useful for diagnosis and follow-up in pre
      symptomatic and symptomatic patients under treatment. TAKE HOME MESSAGE: Muscle
      MRI correlates with muscle function in patients with AOPD and could be useful to
      follow-up patients in daily clinic.

PMID- 27711116
TI  - Pressure Infusion Cuff and Blood Warmer during Massive Transfusion: An
      Experimental Study About Hemolysis and Hypothermia.
AB  - BACKGROUND: Blood warmers were developed to reduce the risk of hypothermia
      associated with the infusion of cold blood products. During massive transfusion,
      these devices are used with compression sleeve, which induce a major stress to
      red blood cells. In this setting, the combination of blood warmer and compression
      sleeve could generate hemolysis and harm the patient. We conducted this study to
      compare the impact of different pressure rates on the hemolysis of packed red
      blood cells and on the outlet temperature when a blood warmer set at 41.5 degrees
      C is used. METHODS: Pressure rates tested were 150 and 300 mmHg. Ten packed red
      blood cells units were provided by Hema-Quebec and each unit was sequentially
      tested. RESULTS: We found no increase in hemolysis either at 150 or 300 mmHg. By
      cons, we found that the blood warmer was not effective at warming the red blood
      cells at the specified temperature. At 150 mmHg, the outlet temperature reached
      37.1 degrees C and at 300 mmHg, the temperature was 33.7 degrees C. CONCLUSION:
      To use a blood warmer set at 41.5 degrees C in conjunction with a compression
      sleeve at 150 or 300 mmHg does not generate hemolysis. At 300 mmHg a blood warmer
      set at 41.5 degrees C does not totally avoid a risk of hypothermia.

PMID- 27711115
TI  - Potency Biomarker Signature Genes from Multiparametric Osteogenesis Assays: Will
      cGMP Human Bone Marrow Mesenchymal Stromal Cells Make Bone?
AB  - In skeletal regeneration approaches using human bone marrow derived mesenchymal
      stromal cells (hBM-MSC), functional evaluation before implantation has
      traditionally used biomarkers identified using fetal bovine serum-based
      osteogenic induction media and time courses of at least two weeks. However,
      emerging pre-clinical evidence indicates donor-dependent discrepancies between
      these ex vivo measurements and the ability to form bone, calling for improved
      tests. Therefore, we adopted a multiparametric approach aiming to generate an
      osteogenic potency assay with improved correlation. hBM-MSC populations from six
      donors, each expanded under clinical-grade (cGMP) conditions, showed
      heterogeneity for ex vivo growth response, mineralization and bone-forming
      ability in a murine xenograft assay. A subset of literature-based biomarker genes
      was reproducibly upregulated to a significant extent across all populations as
      cells responded to two different osteogenic induction media. These 12 biomarkers
      were also measurable in a one-week assay, befitting clinical cell expansion time
      frames and cGMP growth conditions. They were selected for further challenge using
      a combinatorial approach aimed at determining ex vivo and in vivo consistency. We
      identified five globally relevant osteogenic signature genes, notably TGF-beta1
      pathway interactors; ALPL, COL1A2, DCN, ELN and RUNX2. Used in agglomerative
      cluster analysis, they correctly grouped the bone-forming cell populations as
      distinct. Although donor #6 cells were correlation slope outliers, they
      contrastingly formed bone without showing ex vivo mineralization. Mathematical
      expression level normalization of the most discrepantly upregulated signature
      gene COL1A2, sufficed to cluster donor #6 with the bone-forming classification.
      Moreover, attenuating factors causing genuine COL1A2 gene down-regulation,
      restored ex vivo mineralization. This suggested that the signature gene had an
      osteogenically influential role; nonetheless no single biomarker was fully
      deterministic whereas all five signature genes together led to accurate cluster
      analysis. We show proof of principle for an osteogenic potency assay providing
      early characterization of primary cGMP-hBM-MSC cultures according to their donor
      specific bone-forming potential.

PMID- 27711117
TI  - De novo Analysis of the Epiphytic Transcriptome of the Cucurbit Powdery Mildew
      Fungus Podosphaera xanthii and Identification of Candidate Secreted Effector
      Proteins.
AB  - The cucurbit powdery mildew fungus Podosphaera xanthii is a major limiting factor
      for cucurbit production worldwide. Despite the fungus's agronomic and economic
      importance, very little is known about fundamental aspects of P. xanthii biology,
      such as obligate biotrophy or pathogenesis. To design more durable control
      strategies, genomic information about P. xanthii is needed. Powdery mildews are
      fungal pathogens with large genomes compared with those of other fungi, which
      contain vast amounts of repetitive DNA sequences, much of which is composed of
      retrotransposons. To reduce genome complexity, in this work we aimed to obtain
      and analyse the epiphytic transcriptome of P. xanthii as a starting point for
      genomic research. Total RNA was isolated from epiphytic fungal material, and the
      corresponding cDNA library was sequenced using a 454 GS FLX platform. Over
      676,562 reads were obtained and assembled into 37,241 contigs. Annotation data
      identified 8,798 putative genes with different orthologues. As described for
      other powdery mildew fungi, a similar set of missing core ascomycete genes was
      found, which may explain obligate biotrophy. To gain insight into the plant
      pathogen relationships, special attention was focused on the analysis of the
      secretome. After this analysis, 137 putative secreted proteins were identified,
      including 53 candidate secreted effector proteins (CSEPs). Consistent with a
      putative role in pathogenesis, the expression profile observed for some of these
      CSEPs showed expression maxima at the beginning of the infection process at 24 h
      after inoculation, when the primary appressoria are mostly formed. Our data mark
      the onset of genomics research into this very important pathogen of cucurbits and
      shed some light on the intimate relationship between this pathogen and its host
      plant.

PMID- 27711118
TI  - A Gram Stain Hands-On Workshop Enhances First Year Medical Students' Technique
      Competency in Comprehension and Memorization.
AB  - BACKGROUND: Laboratory diagnostic tests have an essential role in patient care,
      and the increasing number of medical and health professions schools focusing on
      teaching laboratory medicine to pre-clinical students reflects this importance.
      However, data validating the pedagogical methods that best influence students'
      comprehension and interpretation of diagnostic tests have not been well
      described. The Gram stain is a simple yet significant and frequently used
      diagnostic test in the clinical setting that helps classify bacteria into two
      major groups, Gram positive and negative, based on their cell wall structure.
      METHODS AND FINDINGS: We used this technique to assess which educational
      strategies may improve students' learning and competency in medical diagnostic
      techniques. Hence, in this randomized controlled study, we compared the
      effectiveness of several educational strategies (e.g. workshop, discussion, or
      lecture) in first year medical students' competency in comprehension and
      interpretation of the Gram stain procedure. We demonstrated that a hands-on
      practical workshop significantly enhances students' competency in memorization
      and overall comprehension of the technique. Interestingly, most students
      irrespective of their cohort showed difficulty in answering Gram stain-related
      analytical questions, suggesting that more emphasis should be allocated by the
      instructors to clearly explain the interpretation of the diagnostic test results
      to students in medical and health professional schools. CONCLUSION: This proof of
      principle study highlights the need of practical experiences on laboratory
      medical techniques during pre-clinical training to facilitate future medical
      doctors' and healthcare professionals' basic understanding and competency in
      diagnostic testing for better patient care.

PMID- 27711119
TI  - Clinical and Wear Analyses of 9 Large Metal-on-Metal Total Hip Prostheses.
AB  - BACKGROUND: Metal-on-Metal (MoM) total hip arthroplasties (THA) are associated
      with pseudotumor formation and high revision rates. This prospective study
      analysed the clinical and wear analyses of 9 large Metal-on-Metal (MoM) total hip
      arthroplasties (THA) to understand the underlying mechanisms of failure. The MoM
      bearings were revised for multiple reasons; the main reason was pseudotumor
      formation. MATERIALS AND METHODS: From 2006 till 2010 the Reinier de Graaf
      Hospital implanted 160 large head M2a-MagnumTM (Biomet Inc. Warsaw, Indiana, USA)
      THAs in 150 patients. The first year, 9 bearings were revised and analysed at the
      Biomechanics Section, Hamburg University of Technology, Germany. We performed
      clinical (Harris Hip Score, radiographic analysis, blood cobalt and chromium) and
      wear analysis (implant, tissue and fluid) of the 9 bearings. Since this study did
      not fall under the scope of the Medical Research Involving Human Subjects Act in
      The Netherlands, no ethical approval was necessary. In this prospective study all
      patient details were anonymized by the corresponding author, all other authors
      were blinded during the research and wear analyses. Patients with bilateral MoM
      implants were excluded. RESULTS: The 9 bearings had a median (IQR) survival of
      41.0 (25) months in situ. From these bearings, three showed no noticeable wear.
      The median (IQR) head wear volume was 3.2 (3.6) mm3 and maximum wear depth 0.02
      (0.02) mm. For the cup the median (IQR) wear volume was 0.23 (0.3) mm3 with a
      maximum wear depth of 0.03 (0.05) mm. CONCLUSION: An early identification of
      parameters related to failure of the MoM THA, such as pain, decreased range of
      motion, radiographic changes and high levels of blood cobalt and chromium is of
      great importance for patient's quality of life. Especially now patients and
      surgeons face the long term effects of all these bearings still in situ. This
      study reports the clinical and wear analyses of 9 MoM THA. In the majority of
      this group the reason for revision was pseudotumor formation. Most bearings
      showed signs of wear, however with a great diversity in clinical analysis, in
      inclination angle, serum cobalt and chromium levels as well as wear analysis. For
      a better understanding of the underlying mechanisms related with failure, more
      wear analyses of revised MoM bearings are necessary as well as a frequent follow
      up of the patients with a MoM bearing.

PMID- 27711120
TI  - Development and Validation of a Photographic Method to Use for Dietary Assessment
      in School Settings.
AB  - OBJECTIVE: To develop and validate a photographic method aimed at making
      assessment of dietary intake in school canteens non-obstrusive, practical and
      feasible. METHODS: The study was conducted in two elementary schools representing
      two different school canteen systems; main dish being served by canteen staff
      (Iceland), and complete self-serving (Sweden). Food items in serving and
      leftovers were weighed and photographed. Trained researchers estimated weights of
      food items by viewing the photographs and comparing them with pictures of half
      and full reference portions with known weights. Plates of servings and leftovers
      from 48 children during five school days (n = 448 plates) and a total of 5967
      food items were estimated. The researchers' estimates were then compared with the
      true weight of the foods and the energy content calculated. RESULTS: Weighed and
      estimated amounts correlated across meals both in grams and as total energy
      (0.853-0.977, p<0.001). The agreement between estimated energy content in school
      meals was close to the true measurement from weighed records; on average 4-19
      kcal below true values. Organisation of meal service impacted the efficacy of the
      method as seen in the difference between countries; with Iceland (served by
      canteen staff) having higher rate of acceptable estimates than Sweden (self
      serving), being 95% vs 73% for total amount (g) in serving. Iceland more often
      had serving size between or above the half and full reference plates compared
      with Sweden. CONCLUSIONS: The photographic method provides acceptable estimates
      of food and energy intake in school canteens. However, greater accuracy can be
      expected when foods are served by canteen staff compared with self-serving.

PMID- 27711122
TI  - Prevalence of Drug Resistance Mycobacterium Tuberculosis among Patients Seen in
      Coast Provincial General Hospital, Mombasa, Kenya.
AB  - BACKGROUND: Although prevention and control of spread of multi-drug resistant
      tuberculosis strains is a global challenge, there is paucity of data on the
      prevalence of DR-TB in patients diagnosed with TB in referral hospitals in Kenya.
      The present study assessed patients' characteristics and prevalence of drug
      resistant TB in sputa smear positive TB patients presenting to Coast Provincial
      General Hospital (CPGH) in Mombasa, Kenya. METHODS: Drug resistance was evaluated
      in 258 randomly selected sputa smear TB positive cases between the periods of
      November 2011 to February 2012 at the CPGH-Mombasa. Basic demographic data was
      obtained using administered questionnaires, and clinical history extracted from
      the files. For laboratory analyses, 2mls of sputum was obtained, decontaminated
      and subjected to mycobacteria DNA analyses. Detection of first line drug
      resistance genes was done using MDRTDR plus kit. This was followed with random
      selection of 83 cases for second line drug resistance genes testing using
      Genotype MDRTBsl probe assay kit (HAINS Lifesciences, GmbH, Germany), in which
      ethambutol mutation probes were included. The data was then analyzed using SPSS
      statistical package version 19.0. RESULTS: Male to female ratio was 1:2. Age
      range was 9 to 75 years, with median of 30 years. New treatment cases constituted
      253(98%), among which seven turned out to be PTB negative, and further grouped as
      4 (1.6%) PTB negative and 3(1.1%) NTM. 237(91.7%) new cases were fully
      susceptible to INH and RIF. The remaining, 8 (3.1%) and 1(0.4%) had mono-
      resistance to INH and RIF, respectively. All the retreatment cases were fully
      susceptible to the first line drugs. HIV positivity was found in 48 (18.6%)
      cases, of which 46(17.8%) were co-infected with TB. Of these, 44 (17.1%) showed
      full susceptibility to TB drugs, while 2 (0.8%) were INH resistant. For the
      second line drugs, one case each showed mono resistance to both and FQ. Also, one
      case each showed drug cross poly resistance to both ETH and FQ, with second line
      injectable antibiotics. However, no significant statistical correlation was
      established between TB and resistance to the second line drugs p = 0.855.
      CONCLUSION: The findings of this study showed the existence of resistance to both
      first and second line anti-tubercular drugs, but no MDR-TB and XDR-TB was
      detected among patients attending TB clinic at CPGH using molecular techniques.

PMID- 27711121
TI  - Identification of OmpA-Like Protein of Tannerella forsythia as an O-Linked
      Glycoprotein and Its Binding Capability to Lectins.
AB  - Bacterial glycoproteins are associated with physiological and pathogenic
      functions of bacteria. It remains unclear whether bacterial glycoproteins can
      bind to specific classes of lectins expressed on host cells. Tannerella forsythia
      is a gram-negative oral anaerobe that contributes to the development of
      periodontitis. In this study, we aimed to find lectin-binding glycoproteins in T.
      forsythia. We performed affinity chromatography of wheat germ agglutinin, which
      binds to N-acetylglucosamine (GlcNAc) and sialic acid (Sia), and identified OmpA
      like protein as the glycoprotein that has the highest affinity. Mass spectrometry
      revealed that OmpA-like protein contains O-type N-acetylhexosamine and hexose.
      Fluorometry quantitatively showed that OmpA-like protein contains Sia. OmpA-like
      protein was found to bind to lectins including E-selectin, P-selectin, L
      selectin, Siglec-5, Siglec-9, Siglec-10, and DC-SIGN. The binding of OmpA-like
      protein to these lectins, except for the Siglecs, depends on the presence of
      calcium. N-acetylneuraminic acid (NeuAc), which is the most abundant Sia,
      inhibited the binding of OmpA-like protein to all of these lectins, whereas
      GlcNAc and mannose only inhibited the binding to DC-SIGN. We further found that
      T. forsythia adhered to human oral epithelial cells, which express E-selectin and
      P-selectin, and that this adhesion was inhibited by addition of NeuAc. Moreover,
      adhesion of an OmpA-like protein-deficient T. forsythia strain to the cells was
      reduced compared to that of the wild-type strain. Our findings indicate that OmpA
      like protein of T. forsythia contains O-linked sugar chains that can mediate
      interactions with specific lectins. This interaction is suggested to facilitate
      adhesion of T. forsythia to the surface of host cells.

PMID- 27711123
TI  - Language-Agnostic Reproducible Data Analysis Using Literate Programming.
AB  - A modern biomedical research project can easily contain hundreds of analysis
      steps and lack of reproducibility of the analyses has been recognized as a severe
      issue. While thorough documentation enables reproducibility, the number of
      analysis programs used can be so large that in reality reproducibility cannot be
      easily achieved. Literate programming is an approach to present computer programs
      to human readers. The code is rearranged to follow the logic of the program, and
      to explain that logic in a natural language. The code executed by the computer is
      extracted from the literate source code. As such, literate programming is an
      ideal formalism for systematizing analysis steps in biomedical research. We have
      developed the reproducible computing tool Lir (literate, reproducible computing)
      that allows a tool-agnostic approach to biomedical data analysis. We demonstrate
      the utility of Lir by applying it to a case study. Our aim was to investigate the
      role of endosomal trafficking regulators to the progression of breast cancer. In
      this analysis, a variety of tools were combined to interpret the available data:
      a relational database, standard command-line tools, and a statistical computing
      environment. The analysis revealed that the lipid transport related genes LAPTM4B
      and NDRG1 are coamplified in breast cancer patients, and identified genes
      potentially cooperating with LAPTM4B in breast cancer progression. Our case study
      demonstrates that with Lir, an array of tools can be combined in the same data
      analysis to improve efficiency, reproducibility, and ease of understanding. Lir
      is an open-source software available at github.com/borisvassilev/lir.

PMID- 27711124
TI  - Resources Required for Cervical Cancer Prevention in Low- and Middle-Income
      Countries.
AB  - BACKGROUND: Cervical cancer is the fourth leading cause of cancer death in women,
      with 85% of cases and deaths occurring in developing countries. While organized
      screening programs have reduced cervical cancer incidence in high-income
      countries through detection and treatment of precancerous lesions, the
      implementation of organized screening has not been effective in low-resource
      settings due to lack of infrastructure and limited budgets. Our objective was to
      estimate the cost of comprehensive primary and secondary cervical cancer
      prevention in low- and middle-income countries. METHODS AND FINDINGS: We
      performed a modeling analysis to estimate 1) for girls aged 10 years, the cost of
      2-dose human papillomavirus (HPV) vaccination; and 2) for women aged 30 to 49
      years, the cost of cervical cancer screening (with visual inspection with acetic
      acid (VIA), HPV testing, or cytology) and preventive treatment in 102 low- and
      middle-income countries from 2015 to 2024. We used an Excel-based costing and
      service utilization model to estimate financial costs (2013 US$) based on
      prevalence of HPV, prevalence of precancerous lesions, and screening test
      performance. Where epidemiologic data were unavailable, we extrapolated from
      settings with data using an individual-based microsimulation model of cervical
      carcinogenesis (calibrated to 20 settings) and multivariate regression. Total HPV
      vaccination costs ranged from US$8.6 billion to US$24.2 billion for all scenarios
      considered (immediate, 5-year, or 10-year roll-out; price per dose US$4.55-US$70
      by country income level). The total cost of screening and preventive treatment
      ranged from US$5.1 billion (10-year roll-out, screening once at age 35 years) to
      US$42.3 billion (immediate roll-out, high intensity screening). Limitations of
      this analysis include the assumption of standardized protocols by country income
      level that did not account for the potential presence of multiple screening
      modalities or management strategies within a country, and extrapolation of cost
      and epidemiologic data to settings where data were limited. CONCLUSIONS: The
      estimated cost of comprehensive cervical cancer prevention with 2-dose HPV
      vaccination of 10-year-old girls and screening of women aged 30 to 49 years
      ranges from US$13.7 billion to US$66.5 billion, depending on speed of roll-out,
      vaccine price per dose, and screening test and frequency. Findings demonstrate
      the substantial impact of vaccine price in middle-income countries that are not
      eligible for assistance from Gavi, the Vaccine Alliance. Replacing routine
      cytology with HPV-based screening may reduce total costs. Data on the health
      impact and relative cost-effectiveness of strategies are needed to determine the
      best value for public health dollars.

PMID- 27711125
TI  - Memory Distortion and Its Avoidance: An Event-Related Potentials Study on False
      Recognition and Correct Rejection.
AB  - Memory researchers have long been captivated by the nature of memory distortions
      and have made efforts to identify the neural correlates of true and false
      memories. However, the underlying mechanisms of avoiding false memories by
      correctly rejecting related lures remains underexplored. In this study, we
      employed a variant of the Deese/Roediger-McDermott paradigm to explore neural
      signatures of committing and avoiding false memories. ERP were obtained for True
      recognition, False recognition, Correct rejection of new items, and, more
      importantly, Correct rejection of related lures. With these ERP data, early
      frontal, left-parietal, and late right-frontal old/new effects (associated with
      familiarity, recollection, and monitoring processes, respectively) were analysed.
      Results indicated that there were similar patterns for True and False recognition
      in all three old/new effects analysed in our study. Also, False recognition and
      Correct rejection of related lures activities seemed to share common underlying
      familiarity-based processes. The ERP similarities between False recognition and
      Correct rejection of related lures disappeared when recollection processes were
      examined because only False recognition presented a parietal old/new effect. This
      finding supported the view that actual false recollections underlie false
      memories, providing evidence consistent with previous behavioural research and
      with most ERP and neuroimaging studies. Later, with the onset of monitoring
      processes, False recognition and Correct rejection of related lures waveforms
      presented, again, clearly dissociated patterns. Specifically, False recognition
      and True recognition showed more positive going patterns than Correct rejection
      of related lures signal and Correct rejection of new items signature. Since False
      recognition and Correct rejection of related lures triggered familiarity
      recognition processes, our results suggest that deciding which items are studied
      is based more on recollection processes, which are later supported by monitoring
      processes. Results are discussed in terms of Activation-Monitoring Framework and
      Fuzzy Trace-Theory, the most prominent explanatory theories of false memory
      raised with the Deese/Roediger-McDermott paradigm.

PMID- 27711127
TI  - Influencing Busy People in a Social Network.
AB  - We identify influential early adopters in a social network, where individuals are
      resource constrained, to maximize the spread of multiple, costly behaviors. A
      solution to this problem is especially important for viral marketing. The problem
      of maximizing influence in a social network is challenging since it is
      computationally intractable. We make three contributions. First, we propose a new
      model of collective behavior that incorporates individual intent, knowledge of
      neighbors actions and resource constraints. Second, we show that the multiple
      behavior influence maximization is NP-hard. Furthermore, we show that the problem
      is submodular, implying the existence of a greedy solution that approximates the
      optimal solution to within a constant. However, since the greedy algorithm is
      expensive for large networks, we propose efficient heuristics to identify the
      influential individuals, including heuristics to assign behaviors to the
      different early adopters. We test our approach on synthetic and real-world
      topologies with excellent results. We evaluate the effectiveness under three
      metrics: unique number of participants, total number of active behaviors and
      network resource utilization. Our heuristics produce 15-51% increase in expected
      resource utilization over the naive approach.

PMID- 27711126
TI  - Integrated Left Ventricular Global Transcriptome and Proteome Profiling in Human
      End-Stage Dilated Cardiomyopathy.
AB  - AIMS: The disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are
      still elusive. The present study investigated integrated global transcriptional
      and translational changes in human DCM for disease biomarker discovery. METHODS:
      We used identical myocardial tissues from five DCM hearts compared to five non
      failing (NF) donor hearts for both transcriptome profiling using the ABI high
      density oligonucleotide microarrays and proteome expression with One-Dimensional
      Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the
      Synapt G2 system. RESULTS: We identified 1262 differentially expressed genes
      (DEGs) and 269 proteins (DEPs) between DCM cases and healthy controls. Among the
      most significantly upregulated (>5-fold) proteins were GRK5, APOA2, IGHG3, ANXA6,
      HSP90AA1, and ATP5C1 (p< 0.01). On the other hand, the most significantly
      downregulated proteins were GSTM5, COX17, CAV1 and ANXA3. At least ten entities
      were concomitantly upregulated on the two analysis platforms: GOT1, ALDH4A1,
      PDHB, BDH1, SLC2A11, HSP90AA1, HSP90AB1, H2AFV, HSPA5 and NDUFV1. Gene ontology
      analyses of DEGs and DEPs revealed significant overlap with enrichment of
      genes/proteins related to metabolic process, biosynthetic process, cellular
      component organization, oxidative phosphorylation, alterations in glycolysis and
      ATP synthesis, Alzheimer's disease, chemokine-mediated inflammation and cytokine
      signalling pathways. CONCLUSION: The concomitant use of transcriptome and
      proteome expression to evaluate global changes in DCM has led to the
      identification of sixteen commonly altered entities as well as novel genes,
      proteins and pathways whose cardiac functions have yet to be deciphered. This
      data should contribute towards better management of the disease.

PMID- 27711129
TI  - Sex and Tissue Specificity of Peg3 Promoters.
AB  - The expression of mouse Peg3 (Paternally expressed gene 3) is driven by 4
      promoters, including its main and three alternative promoters. The sexual,
      temporal and spatial specificity of these promoters was characterized in the
      current study. According to the results, the main promoter displays ubiquitous
      expression patterns throughout different stages and tissues. In contrast, the
      expression of Peg3 driven by the alternative promoter U2 was detected mainly in
      muscle and skin, but not in brain, starting from the late embryonic stage,
      revealing its tissue and stage specificity. The expression levels of both the
      main and U2 promoters are also sexually biased: the levels in females start
      higher but become lower than those in males during early postnatal stages. As an
      imprinted locus, the paternal alleles of these promoters are active whereas the
      maternal alleles are silent. Interestingly, deletion of the repressed maternal
      allele of the main promoter has an unusual effect on the opposite paternal
      allele, causing the up-regulation of both the main and U2 promoters. Overall, the
      promoters of Peg3 derive sexually biased and tissue-specific expression patterns.

PMID- 27711128
TI  - Effectiveness of Omega-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver
      Disease: A Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome with
      the main characteristic of diffuse liver cells with fatty changes. The clinical
      evolution of NAFLD includes simple non-alcoholic fatty liver, non-alcoholic
      steatohepatitis (NASH), liver fibrosis and cirrhosis, and even hepatocellular
      carcinoma. METHODS AND FINDINGS: We conducted this review to identify the
      effectiveness of omega-3 polyunsaturated fatty acids (omega-3 PUFA) in NAFLD. We
      searched PubMed, Cochrane Library and Embase. All randomized controlled trials
      (RCTs) of omega-3 PUFA treatment for NAFLD were considered. Two reviewers
      assessed the quality of each study and collected data independently.
      Disagreements were resolved by discussion among the reviewers and any of the
      other authors of the paper. We performed a meta-analysis and reported summary
      estimates of outcomes as inverse variance (IV), fixed or random, with 95%
      confidence intervals (CIs). We included seven RCTs involving 442 patients (227
      for the experimental group and 215 for the control group). All the patients were
      divided into two groups: one treated with omega-3 PUFA and the other was the
      control group (generally placebo). The demographics of the omega-3 PUFA and
      control groups were comparable. Beneficial changes in alanine aminotransferase
      (ALT) (IV 95% CI: -7.61 [-12.83 to -2.39], p = 0.004), total cholesterol (TC) (IV
      95% CI: -13.41 [-21.44 to -5.38], p = 0.001), triglyceride (TG) (IV 95% CI: 
      43.96 [-51.21 to -36.71], p<0.00001) and high-density lipoprotein cholesterol
      (HDL-C) (IV 95% CI: 6.97 [2.05 to 11.90], p = 0.006) favored omega-3 PUFA
      treatment. Omega-3 PUFA tended towards a beneficial effect on aspartate
      aminotransferase (AST) (IV 95% CI: -6.89 [-17.71 to 3.92], p = 0.21), gamma
      glutamyl transferase (GGT) (IV 95% CI: -8.28 [-18.38 to 1.83], p = 0.11) and low
      density lipoprotein cholesterol (LDL-C) (IV 95% CI: -7.13 [-14.26 to 0.0], p =
      0.05). CONCLUSIONS: Supplementation with omega-3 PUFA is a practical and
      effective treatment for NAFLD to decrease ALT, TC and increase HDL-C, especially
      to decrease TG. Omega-3 PUFA also has a tendency toward a beneficial effect on
      AST, GGT and LDL-C. More high-quality, large RCTs are needed to validate our
      findings.

PMID- 27711130
TI  - Highly Diverse Efficacy of Salvage Treatment Regimens for Relapsed or Refractory
      Peripheral T-Cell Lymphoma: A Systematic Review.
AB  - BACKGROUND: The goal of this study was to perform a systematic review to examine
      the efficacy and safety of various salvage therapy regimens on patients with
      relapsed/refractory PTCL. METHOD: The electronic searches were performed using
      PubMed, Cochrane Library, EMBASE, and Web of Science from inception through June
      2015, with search terms related to relapsed/refractory PTCL, salvage chemotherapy
      regimens, and clinical trials. An eligible study met the following inclusion
      criteria: (1) Patients had refractory or relapsed PTCL; (2) drug regimens were
      used for salvage therapy; (3) the study was a clinical trial; (4) the study
      reported on a series of at least 10 patients of PTCL. RESULTS: Of 35 records
      identified, a total of 14 studies were eligible for systematic reviews, and 12
      different salvage regimens were investigated. A total of 618 relapsed/refractory
      PTCL patients were identified. The ORRs ranged from 22% for those treated with
      lenalidomide to 86% for those with brentuximab vedotin. By the three most
      frequent subtypes, the ORRs ranged from 14.2% to 71.5% for patients with the PTCL
      NOS subtype, 8% to 54% for AITL subtypes, and 24% to 86% for the ALCL subtype.
      The medians of DOR, PFS, and OS ranged from 2.5 to 16.6 months, 2.6 to 13.3
      months, and 3.6 to 14.5 months, respectively. The most frequently reported grade
      3 or 4 adverse events (AEs) were hematological AEs, such as neutropenia and
      thrombocytopenia. CONCLUSION: The efficacy of salvage therapy regimens is highly
      diverse for patients with relapsed/refractory PTCL; this heterogeneity in
      therapeutic effects might be due to the diversity in mechanisms, PTCL subtype
      distribution, and/or numbers/profiles of prior therapy. Comparative studies with
      matched pair analysis are warranted for more evidence of the salvage treatment
      effect on relapsed or heavily pretreated patients with PTCL.

PMID- 27711131
TI  - Identification of Yeast Mutants Exhibiting Altered Sensitivity to Valinomycin and
      Nigericin Demonstrate Pleiotropic Effects of Ionophores on Cellular Processes.
AB  - Ionophores such as valinomycin and nigericin are potent tools for studying the
      impact of ion perturbance on cellular functions. To obtain a broader picture
      about molecular components involved in mediating the effects of these drugs on
      yeast cells under respiratory growth conditions, we performed a screening of the
      haploid deletion mutant library covering the Saccharomyces cerevisiae
      nonessential genes. We identified nearly 130 genes whose absence leads either to
      resistance or to hypersensitivity to valinomycin and/or nigericin. The processes
      affected by their protein products range from mitochondrial functions through
      ribosome biogenesis and telomere maintenance to vacuolar biogenesis and stress
      response. Comparison of the results with independent screenings performed by our
      and other laboratories demonstrates that although mitochondria might represent
      the main target for both ionophores, cellular response to the drugs is very
      complex and involves an intricate network of proteins connecting mitochondria,
      vacuoles, and other membrane compartments.

PMID- 27711132
TI  - DNA Methylation Patterns in Rat Mammary Carcinomas Induced by Pre- and Post
      Pubertal Irradiation.
AB  - Several lines of evidence indicate one's age at exposure to radiation strongly
      modifies the risk of radiation-induced breast cancer. We previously reported that
      rat mammary carcinomas induced by pre- and post-pubertal irradiation have
      distinct gene expression patterns, but the changes underlying these differences
      have not yet been characterized. The aim of this investigation was to see if
      differences in CpG DNA methylation were responsible for the differences in gene
      expression between age at exposure groups observed in our previous study. DNA was
      obtained from the mammary carcinomas arising in female Sprague-Dawley rats that
      were either untreated or irradiated (gamma-rays, 2 Gy) during the pre- or post
      pubertal period (3 or 7 weeks old). The DNA methylation was analyzed using CpG
      island microarrays and the results compared to the gene expression data from the
      original study. Global DNA hypomethylation in tumors was accompanied by gene
      specific hypermethylation, and occasionally, by unique tumor-specific patterns.
      We identified methylation-regulated gene expression candidates that distinguished
      the pre- and post-pubertal irradiation tumors, but these represented only 2
      percent of the differentially expressed genes, suggesting that methylation is not
      a major or primary mechanism underlying the phenotypes. Functional analysis
      revealed that the candidate methylation-regulated genes were enriched for stem
      cell differentiation roles, which may be important in mammary cancer development
      and worth further investigation. However, the heterogeneity of human breast
      cancer means that the interpretation of molecular and phenotypic differences
      should be cautious, and take into account the co-variates such as hormone
      receptor status and cell-of-origin that may influence the associations.

PMID- 27711133
TI  - Developing a Deep Brain Stimulation Neuromodulation Network for Parkinson
      Disease, Essential Tremor, and Dystonia: Report of a Quality Improvement Project.
AB  - OBJECTIVE: To develop a process to improve patient outcomes from deep brain
      stimulation (DBS) surgery for Parkinson disease (PD), essential tremor (ET), and
      dystonia. METHODS: We employed standard quality improvement methodology using the
      Plan-Do-Study-Act process to improve patient selection, surgical DBS lead
      implantation, postoperative programming, and ongoing assessment of patient
      outcomes. RESULTS: The result of this quality improvement process was the
      development of a neuromodulation network. The key aspect of this program is
      rigorous patient assessment of both motor and non-motor outcomes tracked
      longitudinally using a REDCap database. We describe how this information is used
      to identify problems and to initiate Plan-Do-Study-Act cycles to address them.
      Preliminary outcomes data is presented for the cohort of PD and ET patients who
      have received surgery since the creation of the neuromodulation network.
      CONCLUSIONS: Careful outcomes tracking is essential to ensure quality in a
      complex therapeutic endeavor like DBS surgery for movement disorders. The REDCap
      database system is well suited to store outcomes data for the purpose of ongoing
      quality assurance monitoring.

PMID- 27711134
TI  - Interaction of Host Nucleolin with Influenza A Virus Nucleoprotein in the Early
      Phase of Infection Limits the Late Viral Gene Expression.
AB  - Influenza A virus nucleoprotein, is a multifunctional RNA-binding protein,
      encoded by segment-5 of the negative sense RNA genome. It serves as a key
      connector between the virus and the host during virus replication. It
      continuously shuttles between the cytoplasm and the nucleus interacting with
      various host cellular factors. In the current study, host proteins interacting
      with nucleoprotein of Influenza A virus of H1N1 2009 pandemic strain were
      identified by co-immunoprecipitation studies followed by MALDI-TOF/MS analysis.
      Here we report the host nucleolin, a major RNA-binding protein of the nucleolus
      as a novel interacting partner to influenza A virus nucleoprotein. We thus,
      explored the implications of this interaction in virus life cycle and our studies
      have shown that these two proteins interact early during infection in the
      cytoplasm of infected cells. Depletion of nucleolin in A549 cells by siRNA
      targeting endogenous nucleolin followed by influenza A virus infection, disrupted
      its interaction with viral nucleoprotein, resulting in increased expression of
      gene transcripts encoding late viral proteins; matrix (M1) and hemagglutinin (HA)
      in infected cells. On the contrary, over expression of nucleolin in cells
      transiently transfected with pEGFP-NCL construct followed by virus infection
      significantly reduced the late viral gene transcripts, and consequently the viral
      titer. Altered expression of late viral genes and titers following manipulation
      of host cellular nucleolin, proposes the functional importance of its interaction
      with nucleoprotein during influenza A virus infection.

PMID- 27711135
TI  - The Effect of Prophylactic Lamivudine plus Adefovir Therapy Compared with
      Lamivudine Alone in Preventing Hepatitis B Reactivation in Lymphoma Patients with
      High Baseline HBV DNA during Chemotherapy.
AB  - Prophylactic antiviral therapy is essential for lymphoma patients with high
      baseline HBV DNA who undergo cytotoxic chemotherapy. However, there are limited
      data on the optimal options. The present study was designed to compare the
      efficacy of prophylactic lamivudine (LAM) with lamivudine plus adefovir dipivoxil
      (LAM+ADV) in preventing hepatitis B virus (HBV) reactivation in lymphoma with,
      pre-chemotherapy HBV DNA load >=2000 IU/ml. We retrospectively analyzed the
      medical records of 86 lymphoma patients with baseline HBV DNA load >=2000 IU/ml
      during chemotherapy and received LAM or LAM+ADV as prophylaxis between January 1,
      2008 and November 30, 2014 at Sun Yat-sen University Cancer Center, China. Sixty
      five patients received LAM and 21 received LAM+ADV. The rate was significantly
      lower in the LAM+ADV group compared with the LAM group for HBV reactivation
      (23.8% vs 55.4%; p = 0.012), while no difference was observed between the two
      groups in patients for HBV-related hepatitis (21.3% vs 33.3%; p   =  0.349), and
      chemotherapy disruption (10.9% vs 19.0%; p = 0.337). In a multivariate analysis
      of factors associated with HBV reactivation in these patients, LAM+ADV treatment
      and HBeAg negative were the independent protective factors. Therefore, LAM+ADV
      should be considered for antiviral prophylaxis in lymphoma patients with pre
      chemotherapy HBV DNA load >=2000 IU/ml. Further study is warranted to confirm
      these findings.

PMID- 27711137
TI  - Comparison Study between Conventional Sequence and Slice-Encoding Metal Artifact
      Correction (SEMAC) in the Diagnosis of Postoperative Complications in Patients
      Receiving Lumbar Inter-Body Fusion and Pedicle Screw Fixation Surgery.
AB  - BACKGROUND AND PURPOSE: Slice-Encoding Metal Artifact Correction (SEMAC) sequence
      is one of the metal artifact reduction techniques of anatomical structure, but
      there has been no report about evaluation of post-operative complications. The
      purpose of this article is to compare the anatomical visibility between fast spin
      echo (FSE) and FSE-SEMAC and to evaluate the additional value of FSE-SEMAC in
      diagnostic confidence of the complications. MATERIALS AND METHODS: We conducted a
      retrospective study with 54 patients who received lumbar spinal surgery and MR
      images including FSE-SEMAC. For the semi-quantitative evaluation, the visibility
      of anatomical structures (neural foramen, bone-inter-body cage interface, central
      canal, nerve root in epidural space, back muscle, and bone-pedicle screw
      interface) was evaluated. For qualitative evaluation, we evaluated FSE and FSE
      with FSE-SEMAC independently, and recorded the diagnostic confidence level of
      post-operative complications. Generalized estimating equation regression analysis
      was used for statistical analysis, and a weighted kappa was used for inter
      observer agreement. RESULTS: Scores of 6 imaging findings with FSE-SEMAC were
      significantly higher than that of FSE (P-value < .0001). Inter-observer
      agreements show good reliability (weighted kappa = 0.45-0.75). Both reviewers
      deemed 37 (reviewer 1) or 19 more (reviewer 2) post-operative complications with
      FSE plus FSE-SEMAC, compared to FSE only. Except for central canal stenosis (P
      value = .2408), diagnostic confidence level for other post-operative
      complications were significantly higher with FSE plus FSE-SEMAC (P-value = .0000)
      than FSE. CONCLUSIONS: FSE-SEMAC significantly reduces image distortion, compared
      to FSE sequence in 3.0-T MR. Also, diagnostic confidence for post-operative
      complications was higher when FSE with additional FSE-SEMAC compared to FSE only.

PMID- 27711136
TI  - Peripersonal Space and Margin of Safety around the Body: Learning Visuo-Tactile
      Associations in a Humanoid Robot with Artificial Skin.
AB  - This paper investigates a biologically motivated model of peripersonal space
      through its implementation on a humanoid robot. Guided by the present
      understanding of the neurophysiology of the fronto-parietal system, we developed
      a computational model inspired by the receptive fields of polymodal neurons
      identified, for example, in brain areas F4 and VIP. The experiments on the iCub
      humanoid robot show that the peripersonal space representation i) can be learned
      efficiently and in real-time via a simple interaction with the robot, ii) can
      lead to the generation of behaviors like avoidance and reaching, and iii) can
      contribute to the understanding the biological principle of motor equivalence.
      More specifically, with respect to i) the present model contributes to
      hypothesizing a learning mechanisms for peripersonal space. In relation to point
      ii) we show how a relatively simple controller can exploit the learned receptive
      fields to generate either avoidance or reaching of an incoming stimulus and for
      iii) we show how the robot can select arbitrary body parts as the controlled end
      point of an avoidance or reaching movement.

PMID- 27711138
TI  - A Potential Magnetic Resonance Imaging Technique Based on Chemical Exchange
      Saturation Transfer for In Vivo gamma-Aminobutyric Acid Imaging.
AB  - PURPOSE: We developed a novel magnetic resonance imaging (MRI) technique based on
      chemical exchange saturation transfer (CEST) for GABA imaging and investigated
      the concentration-dependent CEST effect ofGABA in a rat model of brain tumor with
      blood-brain barrier (BBB) disruption. MATERIALS AND METHODS: All MRI studies were
      performed using a 7.0-T Agilent MRI scanner. Z-spectra for GABA were acquired at
      7.0 T, 37 degrees C, and a pH of 7.0 using varying B1 amplitudes. CEST images of
      phantoms with different concentrations of GABA solutions (pH, 7.0) and other
      metabolites (glutamine, myoinositol, creatinine, and choline) were collected to
      investigate the concentration-dependent CEST effect of GABA and the potential
      contribution from other brain metabolites. CEST maps for GABA in rat brains with
      tumors were collected at baseline and 50 min, 1.5 h, and 2.0 h after the
      injection of GABA solution. RESULTS: The CEST effect of GABA was observed at
      approximately 2.75 parts per million(ppm) downfield from bulk water, and this
      effect increased with an increase in the B1 amplitude and remained steady after
      the B1 amplitude reached 6.0 MUT (255 Hz). The CEST effect of GABA was
      proportional to the GABA concentration in vitro. CEST imaging of GABA in a rat
      brain with a tumor and compromised BBB showed a gradual increase in the CEST
      effect after GABA injection. CONCLUSION: The findings of this study demonstrate
      the feasibility and potential of CEST MRI with the optimal B1 amplitude, which
      exhibits excellent spatial and temporal resolutions, to map changes in GABA.

PMID- 27711139
TI  - Dichoptic Metacontrast Masking Functions to Infer Transmission Delay in Optic
      Neuritis.
AB  - Optic neuritis (ON) has detrimental effects on the transmission of neuronal
      signals generated at the earliest stages of visual information processing. The
      amount, as well as the speed of transmitted visual signals is impaired.
      Measurements of visual evoked potentials (VEP) are often implemented in clinical
      routine. However, the specificity of VEPs is limited because multiple cortical
      areas are involved in the generation of P1 potentials, including feedback signals
      from higher cortical areas. Here, we show that dichoptic metacontrast masking can
      be used to estimate the temporal delay caused by ON. A group of 15 patients with
      unilateral ON, nine of which had sufficient visual acuity and volunteered to
      participate, and a group of healthy control subjects (N = 8) were presented with
      flashes of gray disks to one eye and flashes of gray annuli to the corresponding
      retinal location of the other eye. By asking subjects to report the subjective
      visibility of the target (i.e. the disk) while varying the stimulus onset
      asynchrony (SOA) between disk and annulus, we obtained typical U-shaped masking
      functions. From these functions we inferred the critical SOAmax at which the mask
      (i.e. the annulus) optimally suppressed the visibility of the target. ON
      associated transmission delay was estimated by comparing the SOAmax between
      conditions in which the disk had been presented to the affected and the mask to
      the other eye, and vice versa. SOAmax differed on average by 28 ms, suggesting a
      reduction in transmission speed in the affected eye. Compared to previously
      reported methods assessing perceptual consequences of altered neuronal
      transmission speed the presented method is more accurate as it is not limited by
      the observers' ability to judge subtle variations in perceived synchrony.

PMID- 27711140
TI  - Do Resit Exams Promote Lower Investments of Study Time? Theory and Data from a
      Laboratory Study.
AB  - Although many educational institutions allow students to resit exams, a recently
      proposed mathematical model suggests that this could lead to a dramatic reduction
      in study-time investment, especially in rational students. In the current study,
      we present a modification of this model in which we included some well-justified
      assumptions about learning and performance on multiple-choice tests, and we
      tested its predictions in two experiments in which participants were asked to
      invest fictional study time for a fictional exam. Consistent with our model, the
      prospect of a resit exam was found to promote lower investments of study time for
      a first exam and this effect was stronger for participants scoring higher on the
      cognitive reflection test. We also found that the negative effect of resit exams
      on study-time investment was attenuated when access to the resit was made
      uncertain by making it probabilistic or dependent on obtaining a minimal, non
      passing grade for the first attempt. Taken together, these results suggest that
      offering students resit exams may compromise the achievement of learning goals,
      and they raise the more general implication that second chances promote risky
      behavior.

PMID- 27711141
TI  - Mycobacterium tuberculosis Rv2882c Protein Induces Activation of Macrophages
      through TLR4 and Exhibits Vaccine Potential.
AB  - Macrophages constitute the first line of defense against Mycobacterium
      tuberculosis and are critical in linking innate and adaptive immunity. Therefore,
      the identification and characterization of mycobacterial proteins that modulate
      macrophage function are essential for understanding tuberculosis pathogenesis. In
      this study, we identified the novel macrophage-activating protein, Rv2882c, from
      M. tuberculosis culture filtrate proteins. Recombinant Rv2882c protein activated
      macrophages to secrete pro-inflammatory cytokines and express co-stimulatory and
      major histocompatibility complex molecules via Toll-like receptor 4, myeloid
      differentiation primary response protein 88, and Toll/IL-1 receptor-domain
      containing adaptor inducing IFN-beta. Mitogen-activated protein kinases and NF
      kappaB signaling pathways were involved in Rv2882c-induced macrophage activation.
      Further, Rv2882c-treated macrophages induced expansion of the effector/memory T
      cell population and Th1 immune responses. In addition, boosting Bacillus Calmette
      Guerin vaccination with Rv2882c improved protective efficacy against M.
      tuberculosis in our model system. These results suggest that Rv2882c is an
      antigen that could be used for tuberculosis vaccine development.

PMID- 27711142
TI  - A Study of BMP-2-Loaded Bipotential Electrolytic Complex around a Biphasic
      Calcium Phosphate-Derived (BCP) Scaffold for Repair of Large Segmental Bone
      Defect.
AB  - A bipotential polyelectrolyte complex with biphasic calcium phosphate (BCP)
      powder dispersion provides an excellent option for protein adsorption and cell
      attachment and can facilitate enhanced bone regeneration. Application of the
      bipotential polyelectrolyte complex embedded in a spongy scaffold for faster
      healing of large segmental bone defects (LSBD) can be a promising endeavor in
      tissue engineering application. In the present study, a hollow scaffold suitable
      for segmental long bone replacement was fabricated by the sponge replica method
      applying the microwave sintering process. The fabricated scaffold was coated with
      calcium alginate at the shell surface, and genipin-crosslinked chitosan with
      biphasic calcium phosphate (BCP) dispersion was loaded at the central hollow
      core. The chitosan core was subsequently loaded with BMP-2. The electrolytic
      complex was characterized using SEM, porosity measurement, FTIR spectroscopy and
      BMP-2 release for 30 days. In vitro studies such as MTT, live/dead, cell
      proliferation and cell differentiation were performed. The scaffold was implanted
      into a 12 mm critical size defect of a rabbit radius. The efficacy of this
      complex is evaluated through an in vivo study, one and two month post
      implantation. BV/TV ratio for BMP-2 loaded sample was (42+/-1.76) higher compared
      with hollow BCP scaffold (32+/-0.225).

PMID- 27711143
TI  - Targeted Genome Editing via CRISPR in the Pathogen Cryptococcus neoformans.
AB  - Low rates of homologous integration have hindered molecular genetic studies in
      Cryptococcus neoformans over the past 20 years, and new tools that facilitate
      genome manipulation in this important pathogen are greatly needed. To this end,
      we have investigated the use of a Class 2 CRISPR system in C. neoformans
      (formerly C. neoformans var. grubii). We first expressed a derivative of the
      Streptococcus pyogenes Cas9 nuclease in C. neoformans, and showed that it has no
      effect on growth, production of virulence factors in vitro, or virulence in a
      murine inhalation model. In proof of principle experiments, we tested the CAS9
      construct in combination with multiple self-cleaving guide RNAs targeting the
      well-characterized phosphoribosylaminoamidazole carboxylase-encoding ADE2 gene.
      Utilizing combinations of transient and stable expression of our constructs, we
      revealed that functionality of our CRISPR constructs in C. neoformans is
      dependent upon the CAS9 construct being stably integrated into the genome, whilst
      transient expression of the guide RNA is sufficient to enhance rates of
      homologous recombination in the CAS9 genetic background. Given that the presence
      of the CRISPR nuclease does not influence virulence in a murine inhalation model,
      we have successfully demonstrated that this system is compatible with studies of
      C. neoformans pathogenesis and represents a powerful tool that can be exploited
      by researchers in the field.

PMID- 27711144
TI  - Accelerated Training of Skilled Birth Attendants in a Marginalized Population on
      the Thai-Myanmar Border: A Multiple Methods Program Evaluation.
AB  - BACKGROUND: To evaluate a skilled birth attendant (SBA) training program in a
      neglected population on the Thai-Myanmar border, we used multiple methods to show
      that refugee and migrant health workers can be given effective training in their
      own environment to become SBAs and teachers of SBAs. The loss of SBAs through
      resettlement to third countries necessitated urgent training of available workers
      to meet local needs. METHODS AND FINDINGS: All results were obtained from student
      records of theory grades and clinical log books. Qualitative evaluation of both
      the SBA and teacher programs was obtained using semi-structured interviews with
      supervisors and teachers. We also reviewed perinatal indicators over an eight
      year period, starting prior to the first training program until after the
      graduation of the fourth cohort of SBAs. RESULTS: Four SBA training programs
      scheduled between 2009 and 2015 resulted in 79/88 (90%) of students successfully
      completing a training program of 250 theory hours and 625 supervised clinical
      hours. All 79 students were able to: achieve pass grades on theory examination
      (median 80%, range [70-89]); obtain the required clinical experience within
      twelve months; achieve clinical competence to provide safe care during
      childbirth. In 2010-2011, five experienced SBAs completed a train-the-trainer
      (TOT) program and went on to facilitate further training programs. Perinatal
      indicators within Shoklo Malaria Research Unit (SMRU), such as place of birth,
      maternal and newborn outcomes, showed no significant differences before and after
      introduction of training or following graduate deployment in the local maternity
      units. Confidence, competence and teamwork emerged from qualitative evaluation by
      senior SBAs working with and supervising students in the clinics. CONCLUSIONS: We
      demonstrate that in resource-limited settings or in marginalized populations, it
      is possible to accelerate training of skilled birth attendants to provide safe
      maternity care. Education needs to be tailored to local needs to ensure evidence
      based care of women and their families.

PMID- 27711145
TI  - Interaction of Staphylococci with Human B cells.
AB  - Staphylococcus aureus is a leading cause of human infections worldwide. The
      pathogen produces numerous molecules that can interfere with recognition and
      binding by host innate immune cells, an initial step required for the ingestion
      and subsequent destruction of microbes by phagocytes. To better understand the
      interaction of this pathogen with human immune cells, we compared the association
      of S. aureus and S. epidermidis with leukocytes in human blood. We found that a
      significantly greater proportion of B cells associated with S. epidermidis
      relative to S. aureus. Complement components and complement receptors were
      important for the binding of B cells with S. epidermidis. Experiments using
      staphylococci inactivated by ultraviolet radiation and S. aureus isogenic
      deletion mutants indicated that S. aureus secretes molecules regulated by the
      SaeR/S two-component system that interfere with the ability of human B cells to
      bind this bacterium. We hypothesize that the relative inability of B cells to
      bind S. aureus contributes to the microbe's success as a human pathogen.

PMID- 27711146
TI  - Distribution and Structure of Synapses on Medial Vestibular Nuclear Neurons
      Targeted by Cerebellar Flocculus Purkinje Cells and Vestibular Nerve in Mice:
      Light and Electron Microscopy Studies.
AB  - Adaptations of vestibulo-ocular and optokinetic response eye movements have been
      studied as an experimental model of cerebellum-dependent motor learning. Several
      previous physiological and pharmacological studies have consistently suggested
      that the cerebellar flocculus (FL) Purkinje cells (P-cells) and the medial
      vestibular nucleus (MVN) neurons targeted by FL (FL-targeted MVN neurons) may
      respectively maintain the memory traces of short- and long-term adaptation. To
      study the basic structures of the FL-MVN synapses by light microscopy (LM) and
      electron microscopy (EM), we injected green florescence protein (GFP)-expressing
      lentivirus into FL to anterogradely label the FL P-cell axons in C57BL/6J mice.
      The FL P-cell axonal boutons were distributed in the magnocellular MVN and in the
      border region of parvocellular MVN and prepositus hypoglossi (PrH). In the
      magnocellular MVN, the FL-P cell axons mainly terminated on somata and proximal
      dendrites. On the other hand, in the parvocellular MVN/PrH, the FL P-cell axonal
      synaptic boutons mainly terminated on the relatively small-diameter (< 1 MUm)
      distal dendrites of MVN neurons, forming symmetrical synapses. The majority of
      such parvocellular MVN/PrH neurons were determined to be glutamatergic by
      immunocytochemistry and in-situ hybridization of GFP expressing transgenic mice.
      To further examine the spatial relationship between the synapses of FL P-cells
      and those of vestibular nerve on the neurons of the parvocellular MVN/PrH, we
      added injections of biotinylated dextran amine into the semicircular canal and
      anterogradely labeled vestibular nerve axons in some mice. The MVN dendrites
      receiving the FL P-cell axonal synaptic boutons often closely apposed vestibular
      nerve synaptic boutons in both LM and EM studies. Such a partial overlap of
      synaptic boutons of FL P-cell axons with those of vestibular nerve axons in the
      distal dendrites of MVN neurons suggests that inhibitory synapses of FL P-cells
      may influence the function of neighboring excitatory synapses of vestibular nerve
      in the parvocellular MVN/PrH neurons.

PMID- 27711147
TI  - Practice Effects on Story Memory and List Learning Tests in the
      Neuropsychological Assessment of Older Adults.
AB  - Two of the most commonly used methods to assess memory functioning in studies of
      cognitive aging and dementia are story memory and list learning tests. We
      hypothesized that the most commonly used story memory test, Wechsler's Logical
      Memory, would generate more pronounced practice effects than a well validated but
      less common list learning test, the Neuropsychological Assessment Battery (NAB)
      List Learning test. Two hundred eighty-seven older adults, ages 51 to 100 at
      baseline, completed both tests as part of a larger neuropsychological test
      battery on an annual basis. Up to five years of recall scores from participants
      who were diagnosed as cognitively normal (n = 96) or with mild cognitive
      impairment (MCI; n = 72) or Alzheimer's disease (AD; n = 121) at their most
      recent visit were analyzed with linear mixed effects regression to examine the
      interaction between the type of test and the number of times exposed to the test.
      Other variables, including age at baseline, sex, education, race, time (years)
      since baseline, and clinical diagnosis were also entered as fixed effects
      predictor variables. The results indicated that both tests produced significant
      practice effects in controls and MCI participants; in contrast, participants with
      AD declined or remained stable. However, for the delayed-but not the immediate
      recall condition, Logical Memory generated more pronounced practice effects than
      NAB List Learning (b = 0.16, p < .01 for controls). These differential practice
      effects were moderated by clinical diagnosis, such that controls and MCI
      participants-but not participants with AD-improved more on Logical Memory delayed
      recall than on delayed NAB List Learning delayed recall over five annual
      assessments. Because the Logical Memory test is ubiquitous in cognitive aging and
      neurodegenerative disease research, its tendency to produce marked practice
      effects-especially on the delayed recall condition-suggests a threat to its
      validity as a measure of new learning, an essential construct for dementia
      diagnosis.

PMID- 27711149
TI  - Spatial Effects on the Multiplicity of Plasmodium falciparum Infections.
AB  - As malaria is being pushed back on many frontiers and global case numbers are
      declining, accurate measurement and prediction of transmission becomes
      increasingly difficult. Low transmission settings are characterised by high
      levels of spatial heterogeneity, which stands in stark contrast to the widely
      used assumption of spatially homogeneous transmission used in mathematical
      transmission models for malaria. In the present study an individual-based
      mathematical malaria transmission model that incorporates multiple parasite
      clones, variable human exposure and duration of infection, limited mosquito
      flight distance and most importantly geographically heterogeneous human and
      mosquito population densities was used to illustrate the differences between
      homogeneous and heterogeneous transmission assumptions when aiming to predict
      surrogate indicators of transmission intensity such as population parasite
      prevalence or multiplicity of infection (MOI). In traditionally highly malaria
      endemic regions where most of the population harbours malaria parasites, humans
      are often infected with multiple parasite clones. However, studies have shown
      also in areas with low overall parasite prevalence, infection with multiple
      parasite clones is a common occurrence. Mathematical models assuming homogeneous
      transmission between humans and mosquitoes cannot explain these observations.
      Heterogeneity of transmission can arise from many factors including acquired
      immunity, body size and occupational exposure. In this study, we show that
      spatial heterogeneity has a profound effect on predictions of MOI and parasite
      prevalence. We illustrate, that models assuming homogeneous transmission
      underestimate average MOI in low transmission settings when compared to field
      data and that spatially heterogeneous models predict stable transmission at much
      lower overall parasite prevalence. Therefore it is very important that models
      used to guide malaria surveillance and control strategies in low transmission and
      elimination settings take into account the spatial features of the specific
      target area, including human and mosquito vector distribution.

PMID- 27711150
TI  - The Association of Current Violence from Adult Family Members with Adolescent
      Bullying Involvement and Suicidal Feelings.
AB  - Although several studies have reported that child physical abuse increased the
      risk for bullying involvement, the effect of current violence from adult family
      members (CVA) on bullying involvement and suicidal feelings among adolescents has
      not been sufficiently examined. This study investigated the association of CVA
      with adolescent bullying involvement and the interaction effect of CVA and
      bullying involvement on suicidal feelings. This cross-sectional study used data
      from a school-based survey with a general population of adolescents (grades 7 to
      12). Data were collected using a self-report questionnaire completed by 17,530
      students. Logistic regression analyses were performed to explore the association
      of CVA with adolescent bullying involvement and suicidal feelings. The overall
      response rate was 90.2%. The odds of students being characterized as bullies,
      victims, and bully-victims were higher among adolescents with CVA than without
      CVA (odds ratios (OR) = 2.9, 95% confidence interval (CI), [2.3-3.7], 4.6 [3.6
      5.8], and 5.8 [4.4-7.6], respectively). Both CVA (OR = 3.4 [95% CI 2.7-4.3]) and
      bullying (bullies, victims, and bully-victims; OR = 2.0 [95% CI 1.6-2.6], 4.0
      [3.1-5.1], 4.1 [3.0-5.6], respectively), were associated with increased odds of
      current suicidal feelings after adjusting for confounding factors. Furthermore,
      positive additive effects of CVA and all three types of bullying involvement on
      suicidal feelings were found. For example, bully-victims with CVA had about 19
      fold higher odds of suicidal feelings compared with uninvolved adolescents
      without CVA. This study, although correlational, suggested that CVA avoidance
      might prevent bullying involvement and suicidal feelings in adolescents.

PMID- 27711148
TI  - Altered Modulation of Silent Period in Tongue Motor Cortex of Persistent
      Developmental Stuttering in Relation to Stuttering Severity.
AB  - Motor balance in developmental stuttering (DS) was investigated with Transcranial
      Magnetic Stimulation (TMS), with the aim to define novel neural markers of
      persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on
      tongue primary motor cortex, compared to 15 matched fluent speakers, in a "state"
      condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and
      silent period thresholds (SPT), recruitment curves, and silent period durations
      were acquired by recording tongue motor evoked potentials. Tongue silent period
      duration was increased in DS, especially in the left hemisphere (P<0.05; Hedge's
      g or Cohen's dunbiased = 1.054, i.e. large effect size), suggesting a "state"
      condition of higher intracortical inhibition in left motor cortex networks.
      Differences in motor thresholds (different excitatory/inhibitory ratios in DS)
      were evident, as well as significant differences in SPT. In fluent speakers, the
      left hemisphere may be marginally more excitable than the right one in motor
      thresholds at lower muscular activation, while active motor thresholds and SPT
      were higher in the left hemisphere of DS with respect to the right one, resulting
      also in a positive correlation with stuttering severity. Pre-TMS electromyography
      data gave overlapping evidence. Findings suggest the existence of a complex
      intracortical balance in DS tongue primary motor cortex, with a particular
      interplay between excitatory and inhibitory mechanisms, also in neural substrates
      related to silent periods. Findings are discussed with respect to functional and
      structural impairments in stuttering, and are also proposed as novel neural
      markers of a stuttering "state" in persistent DS, helping to define more focused
      treatments (e.g. neuro-modulation).

PMID- 27711152
TI  - Throat Swabs and Sputum Culture as Predictors of P. aeruginosa or S. aureus Lung
      Colonization in Adult Cystic Fibrosis Patients.
AB  - BACKGROUND: Due to frequent infections in cystic fibrosis (CF) patients, repeated
      respiratory cultures are obtained to inform treatment. When patients are unable
      to expectorate sputum, clinicians obtain throat swabs as a surrogate for lower
      respiratory cultures. There is no clear data in adult subjects demonstrating the
      adequacy of throat swabs as a surrogate for sputum or BAL. Our study was designed
      to determine the utility of throat swabs in identifying lung colonization with
      common organisms in adults with CF. METHODS: Adult CF subjects (n = 20) underwent
      bronchoscopy with BAL. Prior to bronchoscopy, a throat swab was obtained. A
      sputum sample was obtained from subjects who were able to spontaneously
      expectorate. All samples were sent for standard microbiology culture. RESULTS:
      Using BAL as the gold standard, we found the positive predictive value for
      Pseudomonas aeruginosa to be 100% in both sputum and throat swab compared to BAL.
      However, the negative predictive value for P. aeruginosa was 60% and 50% in
      sputum and throat swab, respectively. Conversely, the positive predictive value
      for Staphylococcus aureus was 57% in sputum and only 41% in throat swab and the
      negative predictive value of S. aureus was 100% in sputum and throat swab
      compared to BAL. CONCLUSIONS: Our data show that positive sputum and throat
      culture findings of P. aeruginosa reflect results found on BAL fluid analysis,
      suggesting these are reasonable surrogates to determine lung colonization with P.
      aeruginosa. However, sputum and throat culture findings of S. aureus do not
      appear to reflect S. aureus colonization of the lung.

PMID- 27711151
TI  - Intraocular Pressure Induced Retinal Changes Identified Using Synchrotron
      Infrared Microscopy.
AB  - Infrared (IR) spectroscopy has been used to quantify chemical and structural
      characteristics of a wide range of materials including biological tissues. In
      this study, we examined spatial changes in the chemical characteristics of rat
      retina in response to intraocular pressure (IOP) elevation using synchrotron
      infrared microscopy (SIRM), a non-destructive imaging approach. IOP elevation was
      induced by placing a suture around the eye of anaesthetised rats. Retinal
      sections were collected onto transparent CaF2 slides 10 days following IOP
      elevation. Using combined SIRM spectra and chemical mapping approaches it was
      possible to quantify IOP induced changes in protein conformation and chemical
      distribution in various layers of the rat retina. We showed that 10 days
      following IOP elevation there was an increase in lipid and protein levels in the
      inner nuclear layer (INL) and ganglion cell layer (GCL). IOP elevation also
      resulted in an increase in nucleic acids in the INL. Analysis of SIRM spectra
      revealed a shift in amide peaks to lower vibrational frequencies with a more
      prominent second shoulder, which is consistent with the presence of cell death in
      specific layers of the retina. These changes were more substantial in the INL and
      GCL layers compared with those occurring in the outer nuclear layer. These
      outcomes demonstrate the utility of SIRM to quantify the effect of IOP elevation
      on specific layers of the retina. Thus SIRM may be a useful tool for the study of
      localised tissue changes in glaucoma and other eye diseases.

PMID- 27711154
TI  - Conversion to No-Till Improves Maize Nitrogen Use Efficiency in a Continuous
      Cover Cropping System.
AB  - A two-year experiment was conducted in the field to measure the combined impact
      of tilling and N fertilization on various agronomic traits related to nitrogen
      (N) use efficiency and to grain yield in maize cultivated in the presence of a
      cover crop. Four years after conversion to no-till, a significant increase in N
      use efficiency N harvest index, N remobilization and N remobilization efficiency
      was observed both under no and high N fertilization conditions. Moreover, we
      observed that grain yield and grain N content were higher under no-till
      conditions only when N fertilizers were applied. Thus, agronomic practices based
      on continuous no-till appear to be a promising for increasing N use efficiency in
      maize.

PMID- 27711153
TI  - Fumarate Production by Torulopsis glabrata: Engineering Heterologous Fumarase
      Expression and Improving Acid Tolerance.
AB  - Fumarate is a well-known biomass building block compound. However, the poor
      catalytic efficiency of fumarase is one of the major factors preventing its
      widespread production. To address this issue, we selected residues 159HPND162 of
      fumarase from Rhizopus oryzae as targets for site-directed mutagenesis based on
      molecular docking analysis. Twelve mutants were generated and characterized in
      detail. Kinetic studies showed that the Km values of the P160A, P160T, P160H,
      N161E, and D162W mutants were decreased, whereas Km values of H159Y, H159V,
      H159S, N161R, N161F, D162K, and D162M mutants were increased. In addition, all
      mutants displayed decreased catalytic efficiency except for the P160A mutant,
      whose kcat/Km was increased by 33.2%. Moreover, by overexpressing the P160A
      mutant, the engineered strain T.G-PMS-P160A was able to produce 5.2 g/L fumarate.
      To further enhance fumarate production, the acid tolerance of T.G-PMS-P160A was
      improved by deleting ade12, a component of the purine nucleotide cycle, and the
      resulting strain T.G(?ade12)-PMS-P160A produced 9.2 g/L fumarate. The strategy
      generated in this study opens up new avenues for pathway optimization and
      efficient production of natural products.

PMID- 27711155
TI  - Prevalence of Latent Tuberculosis among Health Care Workers in High Burden
      Countries: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Tuberculosis is one of the leading causes of death worldwide. Twenty
      two high burden countries contributed to the majority of worldwide tuberculosis
      cases in 2015. Health care workers are at high risk of acquiring tuberculosis
      through occupational exposure. OBJECTIVE: To estimate the prevalence of latent
      tuberculosis infection (LTBI) among health care workers in high burden countries.
      METHODS: Databases including MEDLINE (Ovid), EMBASE (Ovid), CINAHL (Ovid) and ISI
      Web of Science (Thompson-Reuters), and grey literature were searched for English
      language records on relevant medical subject headings (MeSH) terms of LTBI and
      health care providers. Literature was systematically reviewed using EPPI
      Reviewer4 software. Prevalence and incidence of LTBI and 95% confidence intervals
      (CI) were reported. Pooled prevalence of LTBI and 95% CI were calculated using
      random-effects meta-analysis models and heterogeneity was assessed using I2
      statistics. Sub-group analysis was conducted to assess the cause of
      heterogeneity. RESULTS: A total of 990 records were identified. Of those, 18
      studies from only 7 high burden countries representing 10,078 subjects were
      included. Tuberculin skin test results were available for 9,545 participants. The
      pooled prevalence of LTBI was 47% (95% CI 34% to 60%, I2 = 99.6%). In subgroup
      analyses according to the country of the study, the pooled prevalence of LTBI was
      lowest in Brazil (37%) and highest in South Africa (64%). The pooled prevalence
      of LTBI among medical and nursing students was 26% (95% CI 6% to 46%, I2 = 99.3%)
      while the prevalence among all types of health care workers was 57% (95% CI 44%
      to 70%, I2 = 99.1%). Incidence of LTBI was available for health care workers in
      four countries. The cumulative incidence ranged from 2.8% in Brazilian medical
      students to 38% among all types of health care workers in South Africa.
      CONCLUSION: The findings of this study suggest that there is a high burden of
      LTBI among health care workers in high burden countries. Adequate infection
      control measures are warranted to prevent and control transmission in health care
      settings.

PMID- 27711156
TI  - In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic
      Clinical Isolates.
AB  - Bacterial infections present a serious challenge to healthcare practitioners due
      to the emergence of resistance to numerous conventional antibacterial drugs.
      Therefore, new bacterial targets and new antimicrobials are unmet medical needs.
      Rhodanine derivatives have been shown to possess potent antimicrobial activity
      via a novel mechanism. However, their potential use as antibacterials has not
      been fully examined. In this study, we determined the spectrum of activity of
      seven rhodanine derivatives (compounds Rh 1-7) against clinical isolates of Gram
      positive and Gram-negative bacterial strains and Candida albicans. We also
      synthesized and tested three additional compounds, ethyl ester and amide of
      rhodanine 2 (Rh 8 and Rh 10, respectively) and ethyl ester of rhodanine 3 (Rh 9)
      to determine the significance of the carboxyl group modification towards
      antibacterial activity and human serum albumin binding. A broth microdilution
      assay confirmed Rh 1-7 exhibit bactericidal activity against Gram-positive
      pathogens. Rh 2 had significant activity against various vancomycin-resistant
      (MIC90 = 4 MUM) and methicillin-resistant (MIC90 = 4 MUM) Staphylococcus aureus
      (VRSA and MRSA), Staphylococcus epidermidis (MIC = 4 MUM) and vancomycin
      resistant Enterococcus (VRE) strains (MIC90 = 8 MUM). The rhodanine compounds
      exhibited potent activity against Bacillus spp., including Bacillus anthracis,
      with MIC range of 2-8 MUM. In addition, they had potent activity against
      Clostridium difficile. The most potent compound, Rh 2, at 4 and 8 times its MIC,
      significantly decreased S. epidermidis biofilm mass by more than 35% and 45%,
      respectively. None of the rhodanine compounds showed antimicrobial activity (MIC
      > 128 MUM) against various 1) Gram-negative pathogens (Acinetobacter baumannii,
      Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Salmonella
      Typhimurium) or 2) strains of Candida albicans (MIC > 64 MUM). The MTS assay
      confirmed that rhodanines were not toxic to mouse murine macrophage (J774.1A) up
      to 64 MUM, human keratinocytes (HaCat) up to 32 MUM, and human ileocecal
      colorectal cell (HRT-18) up to 128 MUM. Overall, these data suggest that certain
      rhodanine compounds may have potential use for the treatment of several multidrug
      resistant Gram-positive bacterial infections.

PMID- 27711157
TI  - Multisite Phosphorylation of NuMA-Related LIN-5 Controls Mitotic Spindle
      Positioning in C. elegans.
AB  - During cell division, the mitotic spindle segregates replicated chromosomes to
      opposite poles of the cell, while the position of the spindle determines the
      plane of cleavage. Spindle positioning and chromosome segregation depend on
      pulling forces on microtubules extending from the centrosomes to the cell cortex.
      Critical in pulling force generation is the cortical anchoring of cytoplasmic
      dynein by a conserved ternary complex of Galpha, GPR-1/2, and LIN-5 proteins in
      C. elegans (Galpha-LGN-NuMA in mammals). Previously, we showed that the polarity
      kinase PKC-3 phosphorylates LIN-5 to control spindle positioning in early C.
      elegans embryos. Here, we investigate whether additional LIN-5 phosphorylations
      regulate cortical pulling forces, making use of targeted alteration of in vivo
      phosphorylated residues by CRISPR/Cas9-mediated genetic engineering. Four
      distinct in vivo phosphorylated LIN-5 residues were found to have critical
      functions in spindle positioning. Two of these residues form part of a 30 amino
      acid binding site for GPR-1, which we identified by reverse two-hybrid screening.
      We provide evidence for a dual-kinase mechanism, involving GSK3 phosphorylation
      of S659 followed by phosphorylation of S662 by casein kinase 1. These LIN-5
      phosphorylations promote LIN-5-GPR-1/2 interaction and contribute to cortical
      pulling forces. The other two critical residues, T168 and T181, form part of a
      cyclin-dependent kinase consensus site and are phosphorylated by CDK1-cyclin B in
      vitro. We applied a novel strategy to characterize early embryonic defects in
      lethal T168,T181 knockin substitution mutants, and provide evidence for
      sequential LIN-5 N-terminal phosphorylation and dephosphorylation in dynein
      recruitment. Our data support that phosphorylation of multiple LIN-5 domains by
      different kinases contributes to a mechanism for spatiotemporal control of
      spindle positioning and chromosome segregation.

PMID- 27711158
TI  - Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T
      Cell Immune Responses to Malaria in Pregnant Women.
AB  - P. vivax infection during pregnancy has been associated with poor outcomes such
      as anemia, low birth weight and congenital malaria, thus representing an
      important global health problem. However, no vaccine is currently available for
      its prevention. Vir genes were the first putative virulent factors associated
      with P. vivax infections, yet very few studies have examined their potential role
      as targets of immunity. We investigated the immunogenic properties of five VIR
      proteins and two long synthetic peptides containing conserved VIR sequences
      (PvLP1 and PvLP2) in the context of the PregVax cohort study including women from
      five malaria endemic countries: Brazil, Colombia, Guatemala, India and Papua New
      Guinea (PNG) at different timepoints during and after pregnancy. Antibody
      responses against all antigens were detected in all populations, with PNG women
      presenting the highest levels overall. P. vivax infection at sample collection
      time was positively associated with antibody levels against PvLP1 (fold-increase:
      1.60 at recruitment -first antenatal visit-) and PvLP2 (fold-increase: 1.63 at
      delivery), and P. falciparum co-infection was found to increase those responses
      (for PvLP1 at recruitment, fold-increase: 2.25). Levels of IgG against two VIR
      proteins at delivery were associated with higher birth weight (27 g increase per
      duplicating antibody levels, p<0.05). Peripheral blood mononuclear cells from PNG
      uninfected pregnant women had significantly higher antigen-specific IFN-gamma TH1
      responses (p=0.006) and secreted less pro-inflammatory cytokines TNF and IL-6
      after PvLP2 stimulation than P. vivax-infected women (p<0.05). These data
      demonstrate that VIR antigens induce the natural acquisition of antibody and T
      cell memory responses that might be important in immunity to P. vivax during
      pregnancy in very diverse geographical settings.

PMID- 27711159
TI  - Poor Linkage to Care Despite Significant Improvement in Access to Early cART in
      Central Poland - Data from Test and Keep in Care (TAK) Project.
AB  - BACKGROUND: The main objective of the TAK project is investigating barriers in
      accessing HIV care after HIV-diagnosis at the CBVCTs of central Poland. Here we
      describe factors associated with and changes over time in linkage to care and
      access to cART. METHOD: Data collected in 2010-2013 in CBVCTs were linked with
      HIV clinics records using unique identifiers. Individuals were followed from the
      day of CBVCTs visit until first clinical visit or 4/06/2014. Cox-proportional
      hazard models were used to identify factors associated with being linked to care
      and starting cART. RESULTS: In total 232 persons were diagnosed HIV-positive and
      144 (62.1% 95%CI: 55.5-68.3) persons were linked to care. There was no change
      over time in linkage to care (p = 0.48), while time to starting cART decreased (p
      = 0.02). Multivariate factors associated with a lower rate of linkage to care
      were hetero/bisexual sexual orientation, lower education, not having an HIV
      positive partner and not using condoms in a stable relationship. Multivariate
      factors associated with starting cART were lower education, recent year of linked
      to care, and first HIV RNA and CD4 cell count. CONCLUSIONS: Benefits of linkage
      to care, measured by access to early treatment, steadily improved in recent
      years. However at least 1 in 3 persons aware of their HIV status in central
      Poland remained outside professional healthcare. Persons at higher risk of
      remaining outside care, thus target population for future interventions, are
      bi/heterosexuals and those with lower levels of education.

PMID- 27711161
TI  - What Is Stopping the Use of Genetically Modified Insects for Disease Control?

PMID- 27711163
TI  - Community-Associated Methicillin-Resistant Staphylococcus aureus: An Enemy amidst
      Us.

PMID- 27711160
TI  - Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver
      Injury.
AB  - Alcoholic liver disease occurs due to chronic, heavy drinking and is driven both
      by metabolic alterations and immune cell activation. Women are at a higher risk
      than men for developing alcohol induced liver injury and this dimorphism is
      reflected in animal models of alcoholic liver disease. The importance of adipose
      tissue in alcoholic liver disease is emerging. Chronic alcohol consumption causes
      adipose tissue inflammation, which can influence liver injury. Sex differences in
      body fat composition are well known. However, it is still unclear if alcohol
      induced adipose tissue inflammation occurs in a sex-dependent manner. Here we
      have employed the clinically relevant NIAAA model of chronic-binge alcohol
      consumption to investigate this sexual dimorphism. We report that female mice
      have greater liver injury than male mice despite lower alcohol consumption.
      Chronic-binge alcohol induces adipose tissue inflammation in vivo in female mice,
      which is illustrated by increased expression of TNFalpha, IL-6, and CCL2,
      compared to only IL-6 induction in male adipose tissue. Further, macrophage
      activation markers such as CD68 as well as the pro-inflammatory activation
      markers CD11b and CD11c were higher in female adipose tissue. Interestingly,
      alcohol induced expression of TLR2, 3, 4, and 9 in female but not male adipose
      tissue, without affecting the TLR adaptor, MyD88. Higher trends of serum
      endotoxin in female mice may likely contribute to adipose tissue inflammation. In
      vitro chronic alcohol-mediated sensitization of macrophages to endotoxin is
      independent of sex. In summary, we demonstrate for the first time that there is a
      sexual dimorphism in alcohol-induced adipose tissue inflammation and female mice
      exhibit a higher degree of inflammation than male mice.

PMID- 27711164
TI  - Partner Disclosure and Early CD4 Response among HIV-Infected Adults Initiating
      Antiretroviral Treatment in Nairobi Kenya.
AB  - BACKGROUND: Disclosure of HIV serostatus can have significant benefits for people
      living with HIV/AIDS. However, there is limited data on whether partner
      disclosure influences ART treatment response. METHODS: We conducted a
      retrospective cohort study of newly diagnosed, ART-naive HIV-infected adults (>18
      years) who enrolled at the Coptic Hope Center in Nairobi, Kenya between January
      1st 2009 and July 1st 2011 and initiated ART within 3 months. Analysis was
      restricted to adults who reported to have either disclosed or not disclosed their
      HIV status to their partner. Analysis of CD4 response at 6 and 12 months post-ART
      was stratified by age group. RESULTS: Among 615 adults newly initiating ART with
      partner disclosure data and 12 month follow-up, mean age was 38 years and 52%
      were male; 76% reported that they had disclosed their HIV-status to their
      partner. Those who disclosed were significantly younger and more likely to be
      married/cohabitating than non-disclosers. At baseline, median CD4 counts were
      similar between disclosure groups. Among younger adults (< 38 years) those who
      disclosed had higher CD4 recovery than those who did not at 6 months post- ART
      (mean difference = 31, 95% CI 3 to 58 p = 0.03) but not at 12 months (mean
      difference = 17, 95% CI -19 to 52, p = 0.4). Among older adults (>= 38years)
      there was no observed difference in CD4 recovery at 6 or 12 months between
      disclosure groups. CONCLUSION: Among younger adults, disclosure of HIV status to
      partners may be associated with CD4 recovery following ART.

PMID- 27711162
TI  - A De Novo Genome Sequence Assembly of the Arabidopsis thaliana Accession
      Niederzenz-1 Displays Presence/Absence Variation and Strong Synteny.
AB  - Arabidopsis thaliana is the most important model organism for fundamental plant
      biology. The genome diversity of different accessions of this species has been
      intensively studied, for example in the 1001 genome project which led to the
      identification of many small nucleotide polymorphisms (SNPs) and small insertions
      and deletions (InDels). In addition, presence/absence variation (PAV), copy
      number variation (CNV) and mobile genetic elements contribute to genomic
      differences between A. thaliana accessions. To address larger genome
      rearrangements between the A. thaliana reference accession Columbia-0 (Col-0) and
      another accession of about average distance to Col-0, we created a de novo next
      generation sequencing (NGS)-based assembly from the accession Niederzenz-1 (Nd
      1). The result was evaluated with respect to assembly strategy and synteny to Col
      0. We provide a high quality genome sequence of the A. thaliana accession (Nd-1,
      LXSY01000000). The assembly displays an N50 of 0.590 Mbp and covers 99% of the
      Col-0 reference sequence. Scaffolds from the de novo assembly were positioned on
      the basis of sequence similarity to the reference. Errors in this automatic
      scaffold anchoring were manually corrected based on analyzing reciprocal best
      BLAST hits (RBHs) of genes. Comparison of the final Nd-1 assembly to the
      reference revealed duplications and deletions (PAV). We identified 826 insertions
      and 746 deletions in Nd-1. Randomly selected candidates of PAV were
      experimentally validated. Our Nd-1 de novo assembly allowed reliable
      identification of larger genic and intergenic variants, which was difficult or
      error-prone by short read mapping approaches alone. While overall sequence
      similarity as well as synteny is very high, we detected short and larger
      (affecting more than 100 bp) differences between Col-0 and Nd-1 based on bi
      directional comparisons. The de novo assembly provided here and additional
      assemblies that will certainly be published in the future will allow to describe
      the pan-genome of A. thaliana.

PMID- 27711165
TI  - Spatiotemporal Dynamics of Dexmedetomidine-Induced Electroencephalogram
      Oscillations.
AB  - An improved understanding of the neural correlates of altered arousal states is
      fundamental for precise brain state targeting in clinical settings. More
      specifically, electroencephalogram recordings are now increasingly being used to
      relate drug-specific oscillatory dynamics to clinically desired altered arousal
      states. Dexmedetomidine is an anesthetic adjunct typically administered in
      operating rooms and intensive care units to produce and maintain a sedative brain
      state. However, a high-density electroencephalogram characterization of the
      neural correlates of the dexmedetomidine-induced altered arousal state has not
      been previously accomplished. Therefore, we administered dexmedetomidine (1mcg/kg
      bolus over 10 minutes, followed by 0.7mcg/kg/hr over 50 minutes) and recorded
      high-density electroencephalogram signals in healthy volunteers, 18-36 years old
      (n = 8). We analyzed the data with multitaper spectral and global coherence
      methods. We found that dexmedetomidine was associated with increased slow-delta
      oscillations across the entire scalp, increased theta oscillations in occipital
      regions, increased spindle oscillations in frontal regions, and decreased beta
      oscillations across the entire scalp. The theta and spindle oscillations were
      globally coherent. During recovery from this state, these electroencephalogram
      signatures reverted towards baseline signatures. We report that dexmedetomidine
      induced electroencephalogram signatures more closely approximate the human sleep
      onset process than previously appreciated. We suggest that these signatures may
      be targeted by real time visualization of the electroencephalogram or spectrogram
      in clinical settings. Additionally, these signatures may aid the development of
      control systems for principled neurophysiological based brain-state targeting.

PMID- 27711167
TI  - Correction: Endoscopic Gold Fiducial Marker Placement into the Bladder Wall to
      Optimize Radiotherapy Targeting for Bladder-Preserving Management of Muscle
      Invasive Bladder Cancer: Feasibility and Initial Outcomes.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0089754.].

PMID- 27711166
TI  - Mitochondrial Haplogroup Influences Motor Function in Long-Term HIV-1-Infected
      Individuals.
AB  - Evolutionary divergence of the mitochondrial genome has given rise to distinct
      haplogroups. These haplogroups have arisen in specific geographical locations and
      are responsible for subtle functional changes in the mitochondria that may
      provide an evolutionary advantage in a given environment. Based on these
      functional differences, haplogroups could define disease susceptibility in
      chronic settings. In this study, we undertook a detailed neuropsychological
      analysis of a cohort of long-term HIV-1-infected individuals in conjunction with
      sequencing of their mitochondrial genomes. Stepwise regression analysis showed
      that the best model for predicting both working memory and declarative memory
      were age and years since diagnosis. In contrast, years since diagnosis and sub
      haplogroup were significantly predictive of psychomotor speed. Consistent with
      this, patients with haplogroup L3e obtained better scores on psychomotor speed
      and dexterity tasks when compared to the remainder of the cohort, suggesting that
      this haplogroup provides a protective advantage when faced with the combined
      stress of HIV-1 infection and long-term antiretroviral therapies. Differential
      performance on declarative memory tasks was noted for individuals with other sub
      L haplogroups, but these differences were not as robust as the association
      between L3e and psychomotor speed and dexterity tasks. This work provides
      evidence that mitochondrial haplogroup is related to neuropsychological test
      performance among patients in chronic disease settings such as HIV-1 infection.

PMID- 27711168
TI  - Initial Presentation Sites as Predictors of Herpes Zoster Complications: A
      Nationwide Cohort Study.
AB  - Herpes zoster (HZ) is associated with complications such as postherpetic
      neuralgia (PHN) and HZ ophthalmicus (HZO). However, few studies have focused on
      identifying patients having a high risk of PHN and HZO according to the initial
      presentation sites. The current study investigated these factors in a nationwide
      population-based cohort derived from Taiwan's Longitudinal Health Insurance
      Database. The results indicate that the initial presentation sites can predict
      the complication site of HZ. In this study, elderly patients were found to be
      more susceptible to HZ and were the first to present with neurological signs
      (HZN). Furthermore, compared with patients with HZO and other signs (HZT), those
      with HZN had a higher comorbidity risk. Patients with HZN showed a significantly
      higher visceral complication risk than did those with HZO (adjusted hazard ratio
      [HR] = 1.47, 95% confidence interval [CI] = 1.27-1.71). In addition, patients
      with HZT showed lower risks of ocular and neurological complications than did
      those with HZN after stratification by age and sex (adjusted HR = 0.46, 95% CI =
      0.31-0.68 and HR = 0.73, 95% CI = 0.59-0.91, respectively).

PMID- 27711169
TI  - Chinese Version of the EQ-5D Preference Weights: Applicability in a Chinese
      General Population.
AB  - OBJECTIVES: This study aimed to test the reliability, validity and sensitivity of
      Chinese version of the EQ-5D preference weights in Chinese general people,
      examine the differences between the China value set and the UK, Japan and Korea
      value sets, and provide methods for evaluating and comparing the EQ-5D value sets
      of different countries. METHODS: A random sample of 2984 community residents (15
      years or older) were interviewed using a questionnaire including the EQ-5D scale.
      Level of agreement, convergent validity, known-groups validity and sensitivity of
      the EQ-5D China, United Kingdom (UK), Japan and Korea value sets were determined.
      RESULTS: The mean EQ-5D index scores were significantly (P<0.05) different among
      the UK (0.964), Japan (0.981), Korea (0.987), and China (0.985) weights. High
      level of agreement (intraclass correlations coefficients > 0.75) and convergent
      validity (Pearson's correlation coefficients > 0.95) were found between each
      paired schemes. The EQ-5D index scores discriminated equally well for the four
      versions between levels of 10 known-groups (P< 0.05). The effect size and the
      relative efficiency statistics showed that the China weights had better
      sensitivity. CONCLUSIONS: The China EQ-5D preference weights show equivalent
      psychometric properties with those from the UK, Japan and Korea weights while
      slightly more sensitive to known group differences than those from the Japan and
      Korea weights. Considering both psychometric and sociocultural issues, the China
      scheme should be a priority as an EQ-5D based measure of the health related
      quality of life in Chinese general population.

PMID- 27711172
TI  - NT-proBNP Predicts Cardiovascular Death in the General Population Independent of
      Left Ventricular Mass and Function: Insights from a Large Population-Based Study
      with Long-Term Follow-Up.
AB  - AIMS: B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) predict
      cardiovascular endpoints in patients and all-cause death in the general
      population. This was assigned to their association with clinical cardiac
      remodelling defined as changes in size, shape and function of the heart. The aim
      of this study was to evaluate whether NT-proBNP and BNP were associated with
      cardiovascular and overall death independent of clinical cardiac remodelling
      measured by echocardiography as left ventricular hypertrophy (LVH), diastolic
      dysfunction and left ventricular ejection fraction (EF). METHODS AND RESULTS: In
      a general population-based cohort study from Germany (KORA-S3) with subjects'
      baseline age ranging from 25 to 74 years, cardiac morphology and function were
      assessed as left ventricular mass (LVM), diastolic dysfunction and EF by
      echocardiography and circulating NT-proBNP and BNP were measured at baseline. In
      1,223 subjects with mortality follow-up information, we examined the association
      of baseline NT-proBNP and BNP with cardiovascular mortality (number of deaths =
      52, median follow-up time = 12.9years) using Cox regression without and with
      adjustment for cardiovascular risk factors, LVM, diastolic dysfunction and EF.
      The risk of cardiovascular mortality increased with higher NT-proBNP levels
      measured at baseline (hazard ratio HR = 1.67 per unit increment in logNT-proBNP,
      p = 2.78*10-4, adjusted for age and sex). This increased risk persisted after
      adjustment for cardiovascular risk factors, LVM, diastolic dysfunction and EF (HR
      = 1.73; p = 0.047). When excluding subjects with relevant LVH (LVM to body
      surface area > 149g/m2 in men / 122g/m2 in women), the NT-proBNP association with
      mortality was still significant (n = 1,138; number of deaths = 35; HR = 1.48; p =
      0.04). We found similar results for BNP. CONCLUSION: Our data confirms NT-proBNP
      and BNP as predictor of cardiovascular mortality in a large general population
      based study with long-term follow-up. Our study extends previously published
      population-based studies to younger and potentially healthier individuals without
      relevant LVH, diastolic dysfunction or LVD.

PMID- 27711170
TI  - Health Seeking Behaviour among Individuals with Presumptive Tuberculosis in
      Zambia.
AB  - BACKGROUND: Tuberculosis (TB) prevalence surveys offer a unique opportunity to
      study health seeking behaviour at the population level because they identify
      individuals with symptoms that should ideally prompt a health consultation.
      OBJECTIVE: To assess the health-seeking behaviour among individuals who were
      presumptive TB cases in a national population based TB prevalence survey.
      METHODS: A cross sectional survey was conducted between 2013 and 2014 among 66
      survey clusters in Zambia. Clusters were census supervisory areas (CSAs).
      Participants (presumptive TB cases) were individuals aged 15 years and above;
      having either cough, fever or chest pain for 2 weeks or more; and/or having an
      abnormal or inconclusive chest x-ray image. All survey participants were
      interviewed about symptoms and had a chest X-ray taken. An in-depth interview was
      conducted to collect information on health seeking behaviour and previous TB
      treatment. RESULTS: Of the 6,708 participants, the majority reported at least a
      history of chest pain (3,426; 51.1%) followed by cough (2,405; 35.9%), and fever
      (1,030; 15.4%) for two weeks or more. Only 34.9% (2,340) had sought care for
      their symptoms, mainly (92%) at government health facilities. Of those who sought
      care, 13.9% (326) and 12.1% (283) had chest x-ray and sputum examinations,
      respectively. Those ever treated for TB were 9.6% (644); while 1.7% (114) was
      currently on treatment. The average time (in weeks) from onset of symptoms to
      first care-seeking was 3 for the presumptive TB cases. Males, urban dwellers and
      individuals in the highest wealth quintile were less likely to seek care for
      their symptoms. The likelihood of having ever been treated for TB was highest
      among males, urban dwellers; respondents aged 35-64 years, individuals in the
      highest wealth quintile, or HIV positive. CONCLUSION: Some presumptive TB
      patients delay care-seeking for their symptoms. The health system misses
      opportunities to diagnose TB among those who seek care. Improving health-seeking
      behaviour among males, urban dwellers and those with a higher social economic
      status; and addressing health care lapses in TB case detection is required if TB
      is to be effectively controlled in Zambia.

PMID- 27711171
TI  - Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic
      Tissue of Syrian Hamsters with Bicuspid Aortic Valve.
AB  - Bicuspid aortic valve (BAV) is the most frequent congenital cardiac malformation
      in humans, and appears frequently associated with dilatation of the ascending
      aorta. This association is likely the result of a common aetiology. Currently, a
      Syrian hamster strain with a relatively high (~40%) incidence of BAV constitutes
      the only spontaneous animal model of BAV disease. The characterization of
      molecular alterations in the aorta of hamsters with BAV may serve to identify
      pathophysiological mechanisms and molecular markers of disease in humans. In this
      report, we evaluate the expression of ten candidate reference genes in aortic
      tissue of hamsters in order to identify housekeeping genes for normalization
      using quantitative real time PCR (RT-qPCR) assays. A total of 51 adult (180-240
      days old) and 56 old (300-440 days old) animals were used. They belonged to a
      control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30), or
      to the affected strain of hamsters with TAV (n = 45) or BAV (n = 32). The
      expression stability of the candidate reference genes was determined by RT-qPCR
      using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The
      expression analyses showed that the most stable reference genes for the three
      algorithms employed were Cdkn1beta, G3pdh and Polr2a. We propose the use of
      Cdkn1beta, or both Cdkn1beta and G3pdh as reference genes for mRNA expression
      analyses in Syrian hamster aorta.

PMID- 27711173
TI  - Understanding Healthcare Workers Self-Reported Practices, Knowledge and Attitude
      about Hand Hygiene in a Medical Setting in Rural India.
AB  - AIM: To describe self-reported practices and assess knowledge and attitudes
      regarding hand hygiene among healthcare workers in a rural Indian teaching
      hospital. SETTING: A rural teaching hospital and its associated medical and
      nursing colleges in the district of Ujjain, India. METHOD: The study population
      consisted of physicians, nurses, teaching staff, clinical instructors and nursing
      students. Self-administered questionnaires based on the World Health Organization
      Guidelines on Hand Hygiene in Healthcare were used. RESULTS: Out of 489
      healthcare workers, 259 participated in the study (response rate = 53%). The
      proportion of healthcare workers that reported to 'always' practice hand hygiene
      in the selected situations varied from 40-96% amongst categories. Reported
      barriers to maintaining good hand hygiene were mainly related to high workload,
      scarcity of resources, lack of scientific information and the perception that
      priority is not given to hand hygiene, either on an individual or institutional
      level. Previous training on the topic had a statistically significant association
      with self-reported practice (p = 0.001). Ninety three per cent of the respondents
      were willing to attend training on hand hygiene in the near future. CONCLUSION:
      Self-reported knowledge and adherence varied between situations, but hand hygiene
      practices have the potential to improve if the identified constraints could be
      reduced. Future training should focus on enhancing healthcare workers' knowledge
      and understanding regarding the importance of persistent practice in all
      situations.

PMID- 27711174
TI  - Runaway Competition: A Correction and Extension of Results for a Model of
      Competitive Helping.
AB  - We investigate and generalize an existing model of competitive helping within a
      biological market, first introduced for a population of competing individuals in
      which one individual provides help to all others; the rest compete for the help
      available from this individual by providing help themselves. Our generalized
      model comprises two strategies in which each individual of a specific type
      provides the same amount of help as all other individuals of that type. Each
      individual's fitness function is dependent on this level of help, the cost of
      providing the help, and the fact that help is proportionally reciprocated by
      other individuals. Competitive helping occurs when individuals actively try to
      help more than other individuals. To assess the emergence of equilibrium help
      strategies as adopted by proportions of the population, we examine the
      competition over available help within two settings: replicator dynamics and
      agent-based numerical simulations. To move one step further in our
      generalization, we use the agent-based model to study the N-person competitive
      helping game, where all individuals in the population are heterogeneous with
      respect to help provided. Our results show that helping does not increase
      indefinitely with the population size, as concluded previously, and while there
      are some instances of an increase in help provided as a result of competition,
      this competition can be detrimental to all individuals and in most cases, one
      type simply gives up (thus evolving to a "no help" strategy). The degree to which
      an individual's help is reciprocated by the others in the population has strong
      implications in the long-term behaviour of equilibrium help levels of types of
      individuals (and of individuals themselves); these equilibrium help levels
      diverge from existing conjectures in current literature. Lastly, small amounts of
      passively provided (costless) help results in runaway competition among all
      individuals.

PMID- 27711175
TI  - Genetic Variation in the TAS2R38 Bitter Taste Receptor and Smoking Behaviors.
AB  - Common TAS2R38 taste receptor gene variants specify the ability to taste
      phenylthiocarbamide (PTC), 6-n-propylthiouracil (PROP) and structurally related
      compounds. Tobacco smoke contains a complex mixture of chemical substances of
      varying structure and functionality, some of which activate different taste
      receptors. Accordingly, it has been suggested that non-taster individuals may be
      more likely to smoke because of their inability to taste bitter compounds present
      in tobacco smoke, but results to date have been conflicting. We studied three
      cohorts: 237 European-Americans from the state of Georgia, 1,353 European
      Americans and 2,363 African-Americans from the Dallas Heart Study (DHS), and
      4,973 African-Americans from the Dallas Biobank. Tobacco use data was collected
      and TAS2R38 polymorphisms were genotyped for all participants, and PTC taste
      sensitivity was assessed in the Georgia population. In the Georgia group, PTC
      tasters were less common among those who smoke: 71.5% of smokers were PTC tasters
      while 82.5% of non-smokers were PTC tasters (P = 0.03). The frequency of the
      TAS2R38 PAV taster haplotype showed a trend toward being lower in smokers (38.4%)
      than in non-smokers (43.1%), although this was not statistically significant (P =
      0.31). In the DHS European-Americans, the taster haplotype was less common in
      smokers (37.0% vs. 44.0% in non-smokers, P = 0.003), and conversely the frequency
      of the non-taster haplotype was more common in smokers (58.7% vs. 51.5% in non
      smokers, P = 0.002). No difference in the frequency of these haplotypes was
      observed in African Americans in either the Dallas Heart Study or the Dallas
      Biobank. We conclude that TAS2R38 haplotypes are associated with smoking status
      in European-Americans but not in African-American populations. PTC taster status
      may play a role in protecting individuals from cigarette smoking in specific
      populations.

PMID- 27711176
TI  - Complete Protection against Influenza Virus H1N1 Strain A/PR/8/34 Challenge in
      Mice Immunized with Non-Adjuvanted Novirhabdovirus Vaccines.
AB  - Novirhabdoviruses like Viral Hemorrhagic Septicemia Virus (VHSV) and Infectious
      Hematopoietic Necrosis Virus (IHNV) are fish-infecting Rhabdoviruses belonging to
      the Mononegavirales order. By reverse genetics, we previously showed that a
      recombinant VHSV expressing the West Nile Virus (WNV) E glycoprotein could serve
      as a vaccine platform against WNV. In the current study, we aimed to evaluate the
      potential of the Novirhabdovirus platform as a vaccine against influenza virus.
      Recombinant Novirhabdoviruses, rVHSV-HA and rIHNV-HA, expressing at the viral
      surface the hemagglutinin HA ectodomain were generated and used to immunized
      mice. We showed that mice immunized with either, rVHSV-HA or rIHNV-HA, elicited a
      strong neutralizing antibody response against influenza virus. A complete
      protection was conferred to the immunized mice when challenged with a lethal dose
      of influenza H1N1 A/PR/8/34 virus. Furthermore we showed that although acting as
      inert antigen in mice, since naturally inactivated over 20 degrees C, mice
      immunized with rVHSV-HA or rIHNV-HA in the absence of adjuvant were also
      completely protected from a lethal challenge. Novirhabdoviruses platform are of
      particular interest as vaccines for mammals since they are cost effective to
      produce, relatively easy to generate and very effective to protect immunized
      animals.

PMID- 27711178
TI  - Tobacco Smoke Exposure and Eustachian Tube Disorders in US Children and
      Adolescents.
AB  - OBJECTIVES: To describe the association between active, environmental tobacco
      smoke (ETS) exposure and the prevalence of eustachian tube dysfunction (ETD) in
      the U.S. pediatric population. STUDY DESIGN: Cross-sectional. SETTING: U.S.
      representative demographic and audiometric data from the National Health and
      Nutrition Examination Survey (NHANES);2005-2010. SUBJECTS AND METHODS: The study
      consisted of 2,977 children aged 12-19 years. ETD was defined as middle ear
      pressure <100mm H20. ETS was defined as non-active smoking in individuals with
      serum cotinine over the limit of detection (>=0.015 ng/mL) and <10 ng/mL(N =
      1559). RESULTS: The prevalence of ETD was 6.1%. After multivariate adjustment for
      age, sex, body mass index, education level, ethnicity, or having a cold, sinus
      problem or earache during the last 24 hours, compared to unexposed children, the
      odds ratios (95% confidence interval) of ETD for those exposed to ETS ages 12-15
      in the first, second and third tertile of cotinine concentrations were,
      respectively, 1.38 (0.53-3.60), 0.99 (0.53-3.60) and 2.67 (1.12-6.34). Similarly,
      the odds ratios (95% confidence interval) of ETD for those exposed to ETS ages 16
      19 in the first, second and third tertile of cotinine concentrations were,
      respectively, 1.28 (0.48-3.41), 0.99 (0.40-2.48) and 2.86 (1.19-6.88).
      CONCLUSION: These data suggest that children and adolescents exposed to high
      concentrations of ETS may have an increased prevalence of ETD.

PMID- 27711177
TI  - Structural Basis of the Heterodimer Formation between Cell Shape-Determining
      Proteins Csd1 and Csd2 from Helicobacter pylori.
AB  - Colonization of the human gastric mucosa by Helicobacter pylori requires its high
      motility, which depends on the helical cell shape. In H. pylori, several genes
      (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5, and csd6) play key roles in determining
      the cell shape by alteration of cross-linking or by trimming of peptidoglycan
      stem peptides. H. pylori Csd1, Csd2, and Csd3/HdpA are M23B metallopeptidase
      family members and may act as d,d-endopeptidases to cleave the d-Ala4-mDAP3
      peptide bond of cross-linked dimer muropeptides. Csd3 functions also as the d,d
      carboxypeptidase to cleave the d-Ala4-d-Ala5 bond of the muramyl pentapeptide. To
      provide a basis for understanding molecular functions of Csd1 and Csd2, we have
      carried out their structural characterizations. We have discovered that (i) Csd2
      exists in monomer-dimer equilibrium and (ii) Csd1 and Csd2 form a heterodimer. We
      have determined crystal structures of the Csd2121-308 homodimer and the
      heterodimer between Csd1125-312 and Csd2121-308. Overall structures of Csd1125
      312 and Csd2121-308 monomers are similar to each other, consisting of a helical
      domain and a LytM domain. The helical domains of both Csd1 and Csd2 play a key
      role in the formation of homodimers or heterodimers. The Csd1 LytM domain
      contains a catalytic site with a Zn2+ ion, which is coordinated by three
      conserved ligands and two water molecules, whereas the Csd2 LytM domain has
      incomplete metal ligands and no metal ion is bound. Structural knowledge of these
      proteins sheds light on the events that regulate the cell wall in H. pylori.

PMID- 27711179
TI  - Prevalence, Risk Factors, and Complications of Diabetes in the Kilimanjaro
      Region: A Population-Based Study from Tanzania.
AB  - BACKGROUND: In sub-Saharan Africa, diabetes is a growing burden, yet little is
      known about its prevalence, risk factors, and complications. To address these
      gaps and help inform public health efforts aimed at prevention and treatment, we
      conducted a community-based study assessing diabetes epidemiology. METHODS AND
      FINDINGS: We conducted a stratified, cluster-designed, serial cross-sectional
      household study from 2014-2015 in the Kilimanjaro Region, Tanzania. We used a
      three-stage cluster probability sampling method to randomly select individuals.
      To estimate prevalence, we screened individuals for glucose impairment, including
      diabetes, using hemoglobin A1C. We also screened for hypertension and obesity,
      and to assess for potential complications, individuals with diabetes were
      assessed for retinopathy, neuropathy, and nephropathy. We enrolled 481 adults
      from 346 urban and rural households. The prevalence of glucose impairment was
      21.7% (95% CI 15.2-29.8), which included diabetes (5.7%; 95% CI 3.37-9.47) and
      glucose impairment with increased risk for diabetes (16.0%; 95% CI 10.2-24.0).
      Overweight or obesity status had an independent prevalence risk ratio for glucose
      impairment (2.16; 95% CI 1.39-3.36). Diabetes awareness was low (35.6%), and few
      individuals with diabetes were receiving biomedical treatment (33.3%). Diabetes
      associated complications were common (50.2%; 95% CI 33.7-66.7), including renal
      (12.0%; 95% CI 4.7-27.3), ophthalmic (49.6%; 95% CI 28.6-70.7), and neurological
      (28.8%; 95% CI 8.0-65.1) abnormalities. CONCLUSIONS: In a northern region of
      Tanzania, diabetes is an under-recognized health condition, despite the fact that
      many people either have diabetes or are at increased risk for developing
      diabetes. Most individuals were undiagnosed or untreated, and the prevalence of
      diabetes-associated complications was high. Public health efforts in this region
      will need to focus on reducing modifiable risk factors, which appear to include
      obesity, as well as early detection that includes increasing awareness. These
      findings highlight a growing urgency of diabetes prevention in this region as
      well as the need for treatment, including management of complications.

PMID- 27711180
TI  - Magnaporthe oryzae Glycine-Rich Secretion Protein, Rbf1 Critically Participates
      in Pathogenicity through the Focal Formation of the Biotrophic Interfacial
      Complex.
AB  - Magnaporthe oryzae, the fungus causing rice blast disease, should contend with
      host innate immunity to develop invasive hyphae (IH) within living host cells.
      However, molecular strategies to establish the biotrophic interactions are
      largely unknown. Here, we report the biological function of a M. oryzae-specific
      gene, Required-for-Focal-BIC-Formation 1 (RBF1). RBF1 expression was induced in
      appressoria and IH only when the fungus was inoculated to living plant tissues.
      Long-term successive imaging of live cell fluorescence revealed that the
      expression of RBF1 was upregulated each time the fungus crossed a host cell wall.
      Like other symplastic effector proteins of the rice blast fungus, Rbf1
      accumulated in the biotrophic interfacial complex (BIC) and was translocated into
      the rice cytoplasm. RBF1-knockout mutants (Deltarbf1) were severely deficient in
      their virulence to rice leaves, but were capable of proliferating in abscisic
      acid-treated or salicylic acid-deficient rice plants. In rice leaves, Deltarbf1
      inoculation caused necrosis and induced defense-related gene expression, which
      led to a higher level of diterpenoid phytoalexin accumulation than the wild-type
      fungus did. Deltarbf1 showed unusual differentiation of IH and dispersal of the
      normally BIC-focused effectors around the short primary hypha and the first
      bulbous cell. In the Deltarbf1-invaded cells, symplastic effectors were still
      translocated into rice cells but with a lower efficiency. These data indicate
      that RBF1 is a virulence gene essential for the focal BIC formation, which is
      critical for the rice blast fungus to suppress host immune responses.

PMID- 27711181
TI  - Comparison of Drive Counts and Mark-Resight As Methods of Population Size
      Estimation of Highly Dense Sika Deer (Cervus nippon) Populations.
AB  - Assessing temporal changes in abundance indices is an important issue in the
      management of large herbivore populations. The drive counts method has been
      frequently used as a deer abundance index in mountainous regions. However,
      despite an inherent risk for observation errors in drive counts, which increase
      with deer density, evaluations of the utility of drive counts at a high deer
      density remain scarce. We compared the drive counts and mark-resight (MR) methods
      in the evaluation of a highly dense sika deer population (MR estimates ranged
      between 11 and 53 individuals/km2) on Nakanoshima Island, Hokkaido, Japan,
      between 1999 and 2006. This deer population experienced two large reductions in
      density; approximately 200 animals in total were taken from the population
      through a large-scale population removal and a separate winter mass mortality
      event. Although the drive counts tracked temporal changes in deer abundance on
      the island, they overestimated the counts for all years in comparison to the MR
      method. Increased overestimation in drive count estimates after the winter mass
      mortality event may be due to a double count derived from increased deer movement
      and recovery of body condition secondary to the mitigation of density-dependent
      food limitations. Drive counts are unreliable because they are affected by
      unfavorable factors such as bad weather, and they are cost-prohibitive to repeat,
      which precludes the calculation of confidence intervals. Therefore, the use of
      drive counts to infer the deer abundance needs to be reconsidered.

PMID- 27711182
TI  - Genome-Wide Identification and Characterization of MicroRNAs and Target Genes in
      Lonicera japonica.
AB  - MiRNAs function in post-transcriptional regulation of gene expression and play
      very important roles in plant development. Lonicera japonica is one of the
      important medicinal plants in China. However, few studies on the discovery of
      conserved and novel miRNAs from L. japonica were reported. In this study, we
      employed deep sequencing technology to identify miRNAs in leaf and flower tissues
      of L. japonica. A total of 22.97 million clean reads from flower and leaf tissues
      were obtained, which generated 146 conserved miRNAs distributed in 20 families
      and 110 novel miRNAs. Accordingly, 72 differentially expressed miRNAs (P<=0.001)
      between leaves and flowers and their potential target genes were identified and
      validated. The qRT-PCR validation showed that majority of the differentially
      expressed miRNAs showed significant tissue-specific expression in L. japonica.
      Furthermore, the miRNA-mRNA and mRNA-mRNA regulatory networks were constructed
      using Cytoscape software. Taken together, this study identified a large number of
      miRNAs and target genes in L. japonica, which not only provides the first global
      miRNA expression profiles, but also sheds light on functional genomics research
      on L. japonica in the future.

PMID- 27711183
TI  - XRN1 Is a Species-Specific Virus Restriction Factor in Yeasts.
AB  - In eukaryotes, the degradation of cellular mRNAs is accomplished by Xrn1 and the
      cytoplasmic exosome. Because viral RNAs often lack canonical caps or poly-A
      tails, they can also be vulnerable to degradation by these host exonucleases.
      Yeast lack sophisticated mechanisms of innate and adaptive immunity, but do use
      RNA degradation as an antiviral defense mechanism. One model is that the RNA of
      yeast viruses is subject to degradation simply as a side effect of the intrinsic
      exonuclease activity of proteins involved in RNA metabolism. Contrary to this
      model, we find a highly refined, species-specific relationship between Xrn1p and
      the "L-A" totiviruses of different Saccharomyces yeast species. We show that the
      gene XRN1 has evolved rapidly under positive natural selection in Saccharomyces
      yeast, resulting in high levels of Xrn1p protein sequence divergence from one
      yeast species to the next. We also show that these sequence differences translate
      to differential interactions with the L-A virus, where Xrn1p from S. cerevisiae
      is most efficient at controlling the L-A virus that chronically infects S.
      cerevisiae, and Xrn1p from S. kudriavzevii is most efficient at controlling the L
      A-like virus that we have discovered within S. kudriavzevii. All Xrn1p orthologs
      are equivalent in their interaction with another virus-like parasite, the Ty1
      retrotransposon. Thus, the activity of Xrn1p against totiviruses is not simply an
      incidental consequence of the enzymatic activity of Xrn1p, but rather Xrn1p co
      evolves with totiviruses to maintain its potent antiviral activity and limit
      viral propagation in Saccharomyces yeasts. Consistent with this, we demonstrated
      that Xrn1p physically interacts with the Gag protein encoded by the L-A virus,
      suggesting a host-virus interaction that is more complicated than just Xrn1p
      mediated nucleolytic digestion of viral RNAs.

PMID- 27711184
TI  - A Plaque Disruption Index Identifies Patients with Non-STE-Type 1 Myocardial
      Infarction within 24 Hours of Troponin Positivity.
AB  - BACKGROUND: Markers of plaque destabilization and disruption may have a role in
      identifying non-STE- type 1 Myocardial Infarction in patients presenting with
      troponin elevation. We hypothesized that a plaque disruption index (PDI) derived
      from multiple biomarkers and measured within 24 hours from the first detectable
      troponin in patients with acute non-STE- type 1 MI (NSTEMI-A) will confirm the
      diagnosis and identify these patients with higher specificity when compared to
      individual markers and coronary angiography. METHODS: We examined 4 biomarkers of
      plaque destabilization and disruption: myeloperoxidase (MPO), high-sensitivity
      interleukin-6, myeloid-related protein 8/14 (MRP8/14) and pregnancy-associated
      plasma protein-A (PAPP-A) in 83 consecutive patients in 4 groups: stable non
      obstructive coronary artery disease (CAD), stable obstructive CAD, NSTEMI-A
      (enrolled within 24 hours of troponin positivity), and NSTEMI-L (Late
      presentation NSTEMI, enrolled beyond the 24 hour limit). The PDI was calculated
      and the patients' coronary angiograms were reviewed for evidence of plaque
      disruption. The diagnostic performance of the PDI and angiography were compared.
      RESULTS: Compared to other biomarkers, MPO had the highest specificity (83%) for
      NSTEMI-A diagnosis (P<0.05). The PDI computed from PAPP-A, MRP8/14 and MPO was
      higher in NSTEMI-A patients compared to the other three groups (p<0.001) and had
      the highest diagnostic specificity (87%) with 79% sensitivity and 86% accuracy,
      which were higher compared to those obtained with MPO, but did not reach
      statistical significance (P>0.05 for all comparisons). The PDI had higher
      specificity and accuracy for NSTEMI-A diagnosis compared to coronary angiography
      (P<0.05). CONCLUSIONS: A PDI measured within 24 hour of troponin positivity has
      potential to identify subjects with acute Non-ST-elevation type 1 MI. Additional
      evidence using other marker combinations and investigation in a sufficiently
      large non-selected cohort is warranted to establish the diagnostic accuracy of
      the PDI and its potential role in differentiating type 1 and type 2 MI in
      patients presenting with troponin elevation of uncertain etiology.

PMID- 27711185
TI  - Exit from Synchrony in Joint Improvised Motion.
AB  - Motion synchrony correlates with effective and well-rated human interaction.
      However, people do not remain locked in synchrony; Instead, they repeatedly enter
      and exit synchrony. In many important interactions, such as therapy, marriage and
      parent-infant communication, it is the ability to exit and then re-enter
      synchrony that is thought to build strong relationship. The phenomenon of entry
      into zero-phase synchrony is well-studied experimentally and in terms of
      mathematical modeling. In contrast, exit-from-synchrony is under-studied. Here,
      we focus on human motion coordination, and examine the exit-from-synchrony
      phenomenon using experimental data from the mirror game paradigm, in which people
      perform joint improvised motion, and from human tracking of computer-generated
      stimuli. We present a mathematical mechanism that captures aspects of exit-from
      synchrony in human motion. The mechanism adds a random motion component when the
      accumulated velocity error between the players is small. We introduce this
      mechanism to several models for human coordinated motion, including the widely
      studied HKB model, and the predictor-corrector model of Noy, Dekel and Alon. In
      all models, the new mechanism produces realistic simulated behavior when compared
      to experimental data from the mirror game and from tracking of computer generated
      stimuli, including repeated entry and exit from zero-phase synchrony that
      generates a complexity of motion similar to that of human players. We hope that
      these results can inform future research on exit-from-synchrony, to better
      understand the dynamics of coordinated action of people and to enhance human
      computer and human-robot interaction.

PMID- 27711186
TI  - EGFR-Based Immunoisolation as a Recovery Target for Low-EpCAM CTC Subpopulation.
AB  - Circulating tumour cells (CTCs) play a key role in the metastasis process, as
      they are responsible for micrometastasis and are a valuable tool for monitoring
      patients in real-time. Moreover, efforts to develop new strategies for CTCs
      isolation and characterisation, and the translation of CTCs into clinical
      practice needs to overcome the limitation associated with the sole use of
      Epithelial Cell Adhesion Molecule (EpCAM) expression to purify this tumour cell
      subpopulation. CTCs are rare events in the blood of patients and are believed to
      represent the epithelial population from a primary tumour of epithelial origin,
      thus EpCAM immunoisolation is considered an appropriate strategy. The controversy
      stems from the impact that the more aggressive mesenchymal tumour phenotypes
      might have on the whole CTC population. In this work, we first characterised a
      panel of cell lines representative of tumour heterogeneity, confirming the
      existence of tumour cell subpopulations with restricted epithelial features and
      supporting the limitations of EpCAM-based technologies. We next developed
      customised polystyrene magnetic beads coated with antibodies to efficiently
      isolate the phenotypically different subpopulations of CTCs from the peripheral
      blood mononuclear cells (PBMCs) of patients with metastatic cancer. Besides
      EpCAM, we propose Epidermal Growth Factor Receptor (EGFR) as an additional
      isolation marker for efficient CTCs detection.

PMID- 27711187
TI  - Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive primary
      intracranial brain tumor in adults with a mean survival of 14 to 15 months.
      Aberrant activation of the epidermal growth factor receptor (EGFR) plays a
      significant role in GBM progression, with amplification or overexpression of EGFR
      in 60% of GBM tumors. To target EGFR expressed by GBM, we have developed a
      strategy to deliver the coding sequence for cetuximab, an anti-EGFR antibody,
      directly to the CNS using an adeno-associated virus serotype rh.10 gene transfer
      vector. The data demonstrates that single, local delivery of an anti-EGFR
      antibody by an AAVrh.10 vector coding for cetuximab (AAVrh.10Cetmab) reduces GBM
      tumor growth and increases survival in xenograft mouse models of a human GBM EGFR
      expressing cell line and patient-derived GBM. AAVrh10.CetMab-treated mice
      displayed a reduction in cachexia, a significant decrease in tumor volume and a
      prolonged survival following therapy. Adeno-associated-directed delivery of a
      gene encoding a therapeutic anti-EGFR monoclonal antibody may be an effective
      strategy to treat GBM.

PMID- 27711188
TI  - Immunological Signatures after Bordetella pertussis Infection Demonstrate
      Importance of Pulmonary Innate Immune Cells.
AB  - Effective immunity against Bordetella pertussis is currently under discussion
      following the stacking evidence of pertussis resurgence in the vaccinated
      population. Natural immunity is more effective than vaccine-induced immunity
      indicating that knowledge on infection-induced responses may contribute to
      improve vaccination strategies. We applied a systems biology approach comprising
      microarray, flow cytometry and multiplex immunoassays to unravel the molecular
      and cellular signatures in unprotected mice and protected mice with infection
      induced immunity, around a B. pertussis challenge. Pre-existing systemic memory
      Th1/Th17 cells, memory B-cells, and mucosal IgA specific for Ptx, Vag8, Fim2/3
      were detected in the protected mice 56 days after an experimental infection. In
      addition, pre-existing high activity and reactivation of pulmonary innate cells
      such as alveolar macrophages, M-cells and goblet cells was detected. The pro
      inflammatory responses in the lungs and serum, and neutrophil recruitment in the
      spleen upon an infectious challenge of unprotected mice were absent in protected
      mice. Instead, fast pulmonary immune responses in protected mice led to efficient
      bacterial clearance and harbored potential new gene markers that contribute to
      immunity against B. pertussis. These responses comprised of innate makers, such
      as Clca3, Retlna, Glycam1, Gp2, and Umod, next to adaptive markers, such as CCR6+
      B-cells, CCR6+ Th17 cells and CXCR6+ T-cells as demonstrated by transcriptome
      analysis. In conclusion, besides effective Th1/Th17 and mucosal IgA responses,
      the primary infection-induced immunity benefits from activation of pulmonary
      resident innate immune cells, achieved by local pathogen-recognition. These
      molecular signatures of primary infection-induced immunity provided potential
      markers to improve vaccine-induced immunity against B. pertussis.

PMID- 27711189
TI  - Measuring and Characterizing the Human Nasal Cycle.
AB  - Nasal airflow is greater in one nostril than in the other because of transient
      asymmetric nasal passage obstruction by erectile tissue. The extent of
      obstruction alternates across nostrils with periodicity referred to as the nasal
      cycle. The nasal cycle is related to autonomic arousal and is indicative of
      asymmetry in brain function. Moreover, alterations in nasal cycle periodicity
      have been linked to various diseases. There is therefore need for a tool allowing
      continuous accurate measurement and recording of airflow in each nostril
      separately. Here we provide detailed instructions for constructing such a tool at
      minimal cost and effort. We demonstrate application of the tool in 33 right
      handed healthy subjects, and derive several statistical measures for nasal cycle
      characterization. Using these measures applied to 24-hour recordings we observed
      that: 1: subjects spent slightly longer in left over right nostril dominance
      (left = 2.63 +/- 0.89 hours, right = 2.17 +/- 0.89 hours, t(32) = 2.07, p <
      0.05), 2: cycle duration was shorter in wake than in sleep (wake = 2.02 +/- 1.7
      hours, sleep = 4.5 +/- 1.7 hours, (t(30) = 5.73, p < 0.0001). 3: slower breathing
      was associated with a more powerful cycle (the extent of difference across
      nostrils) (r = 0.4, p < 0.0001), and 4: the cycle was influenced by body posture
      such that lying on one side was associated with greater flow in the contralateral
      nostril (p < 0.002). Finally, we provide evidence for an airflow cycle in each
      nostril alone. These results provide characterization of an easily obtained
      measure that may have diagnostic implications for neurological disease and
      cognitive state.

PMID- 27711190
TI  - The Role of Vitamin D in the Transcriptional Program of Human Pregnancy.
AB  - BACKGROUND: Patterns of gene expression of human pregnancy are poorly understood.
      In a trial of vitamin D supplementation in pregnant women, peripheral blood
      transcriptomes were measured longitudinally on 30 women and used to characterize
      gene co-expression networks. OBJECTIVE: Studies suggest that increased maternal
      Vitamin D levels may reduce the risk of asthma in early life, yet the underlying
      mechanisms have not been examined. In this study, we used a network-based
      approach to examine changes in gene expression profiles during the course of
      normal pregnancy and evaluated their association with maternal Vitamin D levels.
      DESIGN: The VDAART study is a randomized clinical trial of vitamin D
      supplementation in pregnancy for reduction of pediatric asthma risk. The trial
      enrolled 881 women at 10-18 weeks of gestation. Longitudinal gene expression
      measures were obtained on thirty pregnant women, using RNA isolated from
      peripheral blood samples obtained in the first and third trimesters.
      Differentially expressed genes were identified using significance of analysis of
      microarrays (SAM), and clustered using a weighted gene co-expression network
      analysis (WGCNA). Gene-set enrichment was performed to identify major biological
      pathways. RESULTS: Comparison of transcriptional profiles between first and third
      trimesters of pregnancy identified 5839 significantly differentially expressed
      genes (FDR<0.05). Weighted gene co-expression network analysis clustered these
      transcripts into 14 co-expression modules of which two showed significant
      correlation with maternal vitamin D levels. Pathway analysis of these two modules
      revealed genes enriched in immune defense pathways and extracellular matrix
      reorganization as well as genes enriched in notch signaling and transcription
      factor networks. CONCLUSION: Our data show that gene expression profiles of
      healthy pregnant women change during the course of pregnancy and suggest that
      maternal Vitamin D levels influence transcriptional profiles. These alterations
      of the maternal transcriptome may contribute to fetal immune imprinting and
      reduce allergic sensitization in early life. TRIAL REGISTRATION:
      clinicaltrials.gov NCT00920621.

PMID- 27711192
TI  - Structural Insights into the Methylation of C1402 in 16S rRNA by
      Methyltransferase RsmI.
AB  - RsmI and RsmH are conserved S-Adenosylmethionine (AdoMet)-dependent
      methyltransferases (MTases) that are responsible for the 2'-O-methylation and N4
      methylation of C1402 in bacterial 16S rRNA, respectively. Methylation of m4Cm1402
      plays a role in fine-tuning the shape and functions of the P-site to increase the
      decoding fidelity, and was recently found to contribute to the virulence of
      Staphylococcus aureus in host animals. Here we report the 2.20-A crystal
      structure of homodimeric RsmI from Escherichia coli in complex with the cofactor
      AdoMet. RsmI consists of an N-terminal putative RNA-binding domain (NTD) and a C
      terminal catalytic domain (CTD) with a Rossmann-like fold, and belongs to the
      class III MTase family. AdoMet is specifically bound into a negatively charged
      deep pocket formed by both domains by making extensive contacts. Structure-based
      mutagenesis and isothermal titration calorimetry (ITC) assays revealed Asp100 and
      Ala124 are vital for AdoMet-binding. Although the overall fold of RsmI shows
      remarkable similarities to the characterized MTases involved in vitamin B12
      biosynthesis, it exhibits a distinct charge distribution especially around the
      AdoMet-binding pocket because of different substrate specificity. The docking
      model of RsmI-AdoMet-RNA ternary complex suggested a possible base-flipping
      mechanism of the substrate RNA that has been observed in several known RNA
      MTases. Our structural and biochemical studies provide novel insights into the
      catalytic mechanism of C1402 methylation in 16S rRNA.

PMID- 27711191
TI  - Vasodilator-Stimulated Phosphoprotein Activity Is Required for Coxiella burnetii
      Growth in Human Macrophages.
AB  - Coxiella burnetii is an intracellular bacterial pathogen that causes human Q
      fever, an acute flu-like illness that can progress to chronic endocarditis and
      liver and bone infections. Humans are typically infected by aerosol-mediated
      transmission, and C. burnetii initially targets alveolar macrophages wherein the
      pathogen replicates in a phagolysosome-like niche known as the parasitophorous
      vacuole (PV). C. burnetii manipulates host cAMP-dependent protein kinase (PKA)
      signaling to promote PV formation, cell survival, and bacterial replication. In
      this study, we identified the actin regulatory protein vasodilator-stimulated
      phosphoprotein (VASP) as a PKA substrate that is increasingly phosphorylated at
      S157 and S239 during C. burnetii infection. Avirulent and virulent C. burnetii
      triggered increased levels of phosphorylated VASP in macrophage-like THP-1 cells
      and primary human alveolar macrophages, and this event required the Calpha
      subunit of PKA. VASP phosphorylation also required bacterial protein synthesis
      and secretion of effector proteins via a type IV secretion system, indicating the
      pathogen actively triggers prolonged VASP phosphorylation. Optimal PV formation
      and intracellular bacterial replication required VASP activity, as siRNA-mediated
      depletion of VASP reduced PV size and bacterial growth. Interestingly, ectopic
      expression of a phospho-mimetic VASP (S239E) mutant protein prevented optimal PV
      formation, whereas VASP (S157E) mutant expression had no effect. VASP (S239E)
      expression also prevented trafficking of bead-containing phagosomes to the PV,
      indicating proper VASP activity is critical for heterotypic fusion events that
      control PV expansion in macrophages. Finally, expression of dominant negative
      VASP (S157A) in C. burnetii-infected cells impaired PV formation, confirming
      importance of the protein for proper infection. This study provides the first
      evidence of VASP manipulation by an intravacuolar bacterial pathogen via
      activation of PKA in human macrophages.

PMID- 27711193
TI  - Effective L-Tyrosine Hydroxylation by Native and Immobilized Tyrosinase.
AB  - Hydroxylation of L-tyrosine to 3,4-dihydroxyphenylalanine (L-DOPA) by immobilized
      tyrosinase in the presence of ascorbic acid (AH2), which reduces DOPA-quinone to
      L-DOPA, is characterized by low reaction yields that are mainly caused by the
      suicide inactivation of tyrosinase by L-DOPA and AH2. The main aim of this work
      was to compare processes with native and immobilized tyrosinase to identify the
      conditions that limit suicide inactivation and produce substrate conversions to L
      DOPA of above 50% using HPLC analysis. It was shown that immobilized tyrosinase
      does not suffer from partitioning and diffusion effects, allowing a direct
      comparison of the reactions performed with both forms of the enzyme. In typical
      processes, additional aeration was applied and boron ions to produce the L-DOPA
      and AH2 complex and hydroxylamine to close the cycle of enzyme active center
      transformations. It was shown that the commonly used pH 9 buffer increased enzyme
      stability, with concomitant reduced reactivity of 76%, and that under these
      conditions, the maximal substrate conversion was approximately 25 (native) to 30%
      (immobilized enzyme). To increase reaction yield, the pH of the reaction mixture
      was reduced to 8 and 7, producing L-DOPA yields of approximately 95% (native
      enzyme) and 70% (immobilized). A three-fold increase in the bound enzyme load
      achieved 95% conversion in two successive runs, but in the third one, tyrosinase
      lost its activity due to strong suicide inactivation caused by L-DOPA processing.
      In this case, the cost of the immobilized enzyme preparation is not overcome by
      its reuse over time, and native tyrosinase may be more economically feasible for
      a single use in L-DOPA production. The practical importance of the obtained
      results is that highly efficient hydroxylation of monophenols by tyrosinase can
      be obtained by selecting the proper reaction pH and is a compromise between
      complexation and enzyme reactivity.

PMID- 27711195
TI  - Correction: Equality in Maternal and Newborn Health: Modelling Geographic
      Disparities in Utilisation of Care in Five East African Countries.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0162006.].

PMID- 27711194
TI  - Equine Chorionic Gonadotropin Modulates the Expression of Genes Related to the
      Structure and Function of the Bovine Corpus Luteum.
AB  - We hypothesized that stimulatory and superovulatory treatments, using equine
      chorionic gonadotropin (eCG), modulate the expression of genes related to
      insulin, cellular modelling and angiogenesis signaling pathways in the bovine
      corpus luteum (CL). Therefore, we investigated: 1-the effect of these treatments
      on circulating insulin and somatomedin C concentrations and on gene and protein
      expression of INSR, IGF1 and IGFR1, as well as other insulin signaling molecules;
      2-the effects of eCG on gene and protein expression of INSR, IGF1, GLUT4 and
      NFKB1A in bovine luteal cells; and 3-the effect of stimulatory and superovulatory
      treatments on gene and protein expression of ANG, ANGPT1, NOS2, ADM, PRSS2, MMP9
      and PLAU. Serum insulin did not differ among groups (P = 0.96). However, serum
      somatomedin C levels were higher in both stimulated and superovulated groups
      compared to the control (P = 0.01). In stimulated cows, lower expression of INSR
      mRNA and higher expression of NFKB1A mRNA and IGF1 protein were observed. In
      superovulated cows, lower INSR mRNA expression, but higher INSR protein
      expression and higher IGF1, IGFR1 and NFKB1A gene and protein expression were
      observed. Expression of angiogenesis and cellular modelling pathway-related
      factors were as follows: ANGPT1 and PLAU protein expression were higher and MMP9
      gene and protein expression were lower in stimulated animals. In superovulated
      cows, ANGPT1 mRNA expression was higher and ANG mRNA expression was lower. PRSS2
      gene and protein expression were lower in both stimulated and superovulated
      animals related to the control. In vitro, eCG stimulated luteal cells P4
      production as well as INSR and GLUT4 protein expression. In summary, our results
      suggest that superovulatory treatment induced ovarian proliferative changes
      accompanied by increased expression of genes providing the CL more energy
      substrate, whereas stimulatory treatment increased lipogenic activity,
      angiogenesis and plasticity of the extracellular matrix (ECM).

PMID- 27711196
TI  - JAK3 as an Emerging Target for Topical Treatment of Inflammatory Skin Diseases.
AB  - The recent interest and elucidation of the JAK/STAT signaling pathway created new
      targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in
      oral and topical formulations have shown beneficial results in psoriasis and
      alopecia areata. Patients suffering from other ISDs might also benefit from JAK
      inhibition. Given the development of specific JAK inhibitors, the expression
      patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the
      expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis,
      lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD),
      pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for
      (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis
      carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal
      infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were
      significantly overexpressed in PG and AD suggesting the need for pan-JAK
      inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation,
      while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and
      pJAK1, respectively). This indicates that the latter diseases may benefit from
      more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed
      reversal of the psoriatic JAK profile following tofacitinib treatment. This
      direct interaction with keratinocytes may decrease the need for deep skin
      penetration of topical JAK inhibitors in order to exert its effects on dermal
      immune cells. In conclusion, these results point to the important contribution of
      the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression
      levels, great interest should go to the investigation of topical JAK3 inhibitors
      as therapeutic option of ISDs.

PMID- 27711198
TI  - Health Status of Sand Flathead (Platycephalus bassensis), Inhabiting an
      Industrialised and Urbanised Embayment, Port Phillip Bay, Victoria as Measured by
      Biomarkers of Exposure and Effects.
AB  - Port Phillip Bay, Australia, is a large semi-closed bay with over four million
      people living in its catchment basin. The Bay receives waters from the Yarra
      River which drains the city of Melbourne, as well as receiving the discharges of
      sewage treatment plants and petrochemical and agricultural chemicals. A 1999
      study demonstrated that fish inhabiting Port Phillip Bay showed signs of effects
      related to pollutant exposure despite pollution management practices having been
      implemented for over a decade. To assess the current health status of the fish
      inhabiting the Bay, a follow up survey was conducted in 2015. A suite of
      biomarkers of exposure and effects were measured to determine the health status
      of Port Phillip Bay sand flathead (Platycephalus bassensis), namely
      ethoxyresorufin-O-deethylase (EROD) activity, polycyclic aromatic hydrocarbons
      (PAH) biliary metabolites, carboxylesterase activity (CbE) and DNA damage (8-oxo
      dG). The reduction in EROD activity in the present study suggests a decline in
      the presence of EROD activity-inducing chemicals within the Bay since the 1990s.
      Fish collected in the most industrialised/urbanised sites did not display higher
      PAH metabolite levels than those in less developed areas of the Bay. Ratios of
      PAH biliary metabolite types were used to indicate PAH contaminant origin. Ratios
      indicated fish collected at Corio Bay and Hobsons Bay were subjected to increased
      low molecular weight hydrocarbons of petrogenic origin, likely attributed to the
      close proximity of these sites to oil refineries, compared to PAH biliary
      metabolites in fish from Geelong Arm and Mordialloc. Quantification of DNA damage
      indicated a localised effect of exposure to pollutants, with a 10-fold higher DNA
      damage level in fish sampled from the industrial site of Corio Bay relative to
      the less developed site of Sorrento. Overall, integration of biomarkers by
      multivariate analysis indicated that the health of fish collected in
      industrialised areas was compromised, with biologically significant biomarkers of
      effects (LSI, CF and DNA damage) discriminating between individuals collected in
      industrialised areas from observations made in fish collected in less developed
      areas of the Bay.

PMID- 27711197
TI  - A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by
      Synergistic Genetic Cues.
AB  - Heritable epigenetic changes underlie the ability of cells to differentiate into
      distinct cell types. Here, we demonstrate that the fungal pathogen Candida
      tropicalis exhibits multipotency, undergoing stochastic and reversible switching
      between three cellular states. The three cell states exhibit unique cellular
      morphologies, growth rates, and global gene expression profiles. Genetic analysis
      identified six transcription factors that play key roles in regulating cell
      differentiation. In particular, we show that forced expression of Wor1 or Efg1
      transcription factors can be used to manipulate transitions between all three
      cell states. A model for tristability is proposed in which Wor1 and Efg1 are self
      activating but mutually antagonistic transcription factors, thereby forming a
      symmetrical self-activating toggle switch. We explicitly test this model and show
      that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching,
      whereas ectopic expression of EFG1 drives switching in the opposite direction,
      from opaque-to-hybrid-to-white cell states. We also address the stability of
      induced cell states and demonstrate that stable differentiation events require
      ectopic gene expression in combination with chromatin-based cues. These studies
      therefore experimentally test a model of multistate stability and demonstrate
      that transcriptional circuits act synergistically with chromatin-based changes to
      drive cell state transitions. We also establish close mechanistic parallels
      between phenotypic switching in unicellular fungi and cell fate decisions during
      stem cell reprogramming.

PMID- 27711199
TI  - A Randomized Controlled Trial Comparing the Effects of Sitagliptin and
      Glimepiride on Endothelial Function and Metabolic Parameters: Sapporo Athero
      Incretin Study 1 (SAIS1).
AB  - OBJECTIVES: The DPP-4 inhibitors are incretin-related drugs that improve
      hyperglycemia in a glucose-dependent manner and have been reported to exert
      favorable effects on atherosclerosis. However, it has not been fully elucidated
      whether DPP-4 inhibitors are able to improve endothelial function in patients
      with type 2 diabetes. Therefore, we investigated the efficacy of sitagliptin, a
      DPP-4 inhibitor, on endothelial function and glycemic metabolism compared with
      that of the sulfonylurea glimepiride. MATERIALS AND METHODS: In this multicenter,
      prospective, randomized parallel-group comparison study, 103 outpatients with
      type 2 diabetes (aged 59.9 +/- 9.9 years with HbA1c levels of 7.5 +/- 0.4%) with
      dietary cure only and/or current metformin treatment were enrolled and randomly
      assigned to receive sitagliptin or glimepiride therapy once daily for 26 weeks.
      Flow-mediated dilation (FMD), a comprehensive panel of hemodynamic parameters
      (Task Force(r) Monitor), and serum metabolic markers were assessed before and
      after the treatment. RESULTS: During the study period, no statistically
      significant change in %FMD was seen in both groups (sitagliptin, 5.6 to 5.6%;
      glimepiride, 5.6 to 6.0%). Secretory units of islets in transplantation, TNF
      alpha, adiponectin and biological antioxidant potential significantly improved in
      the sitagliptin group, and superoxide dismutase also tended to improve in the
      sitagliptin group, while improvements in HbA1c levels were similar between
      groups. Cardiac index, blood pressure and most other metabolic parameters were
      not different. CONCLUSIONS: Regardless of glycemic improvement, early sitagliptin
      therapy did not affect endothelial function but may provide favorable effects on
      beta-cell function and on inflammatory and oxidative stress in patients with type
      2 diabetes without advanced atherosclerosis. TRIAL REGISTRATION: UMIN Clinical
      Trials Registry System UMIN 000004955.

PMID- 27711200
TI  - Cost-Effectiveness of Hepatitis C Treatment for People Who Inject Drugs and the
      Impact of the Type of Epidemic; Extrapolating from Amsterdam, the Netherlands.
AB  - BACKGROUND: People who inject drugs (PWID) are disproportionally affected by the
      hepatitis C virus (HCV) infection. The efficacy of HCV treatment has
      significantly improved in recent years with the introduction of direct-acting
      antivirals (DAAs). However, DAAs are more costly than pegylated-interferon and
      ribavirin (PegIFN/RBV). We aimed to assess the cost-effectiveness of four HCV
      treatment strategies among PWID and treatment scale-up. METHODS: An individual
      based model was used describing HIV and HCV transmission and disease progression
      among PWID. We considered two epidemiological situations. A declining epidemic,
      based on the situation in Amsterdam, the Netherlands, and a stable HCV epidemic,
      as observed in other settings. Data on HCV incidence, prevalence, treatment
      setting and uptake were derived from observed data among PWID in Amsterdam. We
      assessed the incremental cost-effectiveness ratio (ICER, costs in ?/quality
      adjusted life year (QALY)) of four treatment strategies: 1) PegIFN/RBV; 2)
      sofosbuvir/RBV for genotype 2-3 and dual DAA for genotype 1-4; 3) Dual DAA for
      all genotypes; 4) Dual DAA with 3x treatment uptake. RESULTS: In both types of
      epidemic, dual DAA therapy was most cost-effective strategy. In the declining
      epidemic, dual DAA yielded an ICER of 344 ?/QALY while in the stable epidemic
      dual DAA led to cost-savings. Scaling-up treatment was also highly cost
      effective. Our results were robust over a range of sensitivity analyses.
      CONCLUSION: HCV treatment with DAA-containing regimens is a highly cost-effective
      intervention among PWID. Based on the economic and population benefits of scaling
      up treatment, stronger efforts are needed to achieve higher uptake rates among
      PWID.

PMID- 27711201
TI  - Distinct Effects of p19 RNA Silencing Suppressor on Small RNA Mediated Pathways
      in Plants.
AB  - RNA silencing is one of the main defense mechanisms employed by plants to fight
      viruses. In change, viruses have evolved silencing suppressor proteins to
      neutralize antiviral silencing. Since the endogenous and antiviral functions of
      RNA silencing pathway rely on common components, it was suggested that viral
      suppressors interfere with endogenous silencing pathway contributing to viral
      symptom development. In this work, we aimed to understand the effects of the
      tombusviral p19 suppressor on endogenous and antiviral silencing during genuine
      virus infection. We showed that ectopically expressed p19 sequesters endogenous
      small RNAs (sRNAs) in the absence, but not in the presence of virus infection.
      Our presented data question the generalized model in which the sequestration of
      endogenous sRNAs by the viral suppressor contributes to the viral symptom
      development. We further showed that p19 preferentially binds the perfectly paired
      ds-viral small interfering RNAs (vsiRNAs) but does not select based on their
      sequence or the type of the 5' nucleotide. Finally, co-immunoprecipitation of
      sRNAs with AGO1 or AGO2 from virus-infected plants revealed that p19 specifically
      impairs vsiRNA loading into AGO1 but not AGO2. Our findings, coupled with the
      fact that p19-expressing wild type Cymbidium ringspot virus (CymRSV) overcomes
      the Nicotiana benthamiana silencing based defense killing the host, suggest that
      AGO1 is the main effector of antiviral silencing in this host-virus combination.

PMID- 27711203
TI  - Health-Related Quality of Life in Korean Adults with Hearing Impairment: The
      Korea National Health and Nutrition Examination Survey 2010 to 2012.
AB  - BACKGROUND: As the global population ages, disabling hearing impairment (HI) have
      been increased rapidly. The impact of HI on health-related quality of life
      (HRQoL) is of great importance to aid the development of strategic plans and to
      guide therapeutic interventions. PURPOSE: To evaluate HRQoL in Korean adults with
      different degrees of HI using EuroQol five-dimensional (EQ-5D) and EQ-visual
      analogue scale (VAS), the preference-based generic measures of HRQoL. METHODS:
      Using a representative dataset from the Korea National Health and Nutrition
      Examination Survey (KNHANES) from January 2010 to December 2012, EQ-5D
      questionnaire and EQ- VAS scores of subjects with HI were compared with those of
      subjects without HI. Logistic regression analysis, with adjustment for
      covariates, was used to evaluate the impact of HI on HRQoL scales. HI was defined
      according to the hearing thresholds of pure-tone averages at 0.5, 1, 2, and 3 kHz
      of the better hearing ear as follows; mild HI (26 to < 40 dB) and moderate to
      severe HI (>= 40 dB). RESULTS: Of the 16,449 Korean adults in KNHANES (age, 45.0
      +/- 0.2 years; male, 49.7%), 1757 (weighted prevalence, 7.6%) had mild HI and 890
      (3.6%) had moderate to severe HI. Subjects with HI had impaired HRQoL as compared
      with subjects without HI (EQ-5D, 0.96 +/- 0.00 vs. 0.88+/-0.00 vs. 0.86 +/- 0.01
      for control vs. mild HI vs. moderate to severe HI, p < 0.001; EQ-VAS, 75.10 +/-
      0.18 vs. 67.48 +/- 0.63 vs. 66.24 +/- 0.92 for control vs. mild HI vs. moderate
      to severe HI, p < 0.001). After adjusting for socio-demographic factors (age,
      gender, household income, education level, presence of spouse) and health-related
      behaviors (smoking status, alcohol intake, regular exercise), psychological
      stress, and the presence of comorbidities (diabetes, hypercholesterolemia,
      hypertension, decreased eGFR, and tinnitus), EQ-VAS remained impaired in the
      moderate to severe HI group (61.72+/-1.69) as compared with the control group
      (65.68 +/- 1.26, p = 0.004), but EQ-5D impairment disappeared (0.86 +/- 0.02
      vs.0.88+/-0.01 for moderate to severe HI vs. control, p = 0.058). CONCLUSION:
      After adjusting for socio-demographic and psychosocial factors and comorbidities,
      Korean adults with moderate to severe HI rated their health statuses lower than
      subjects without HI.

PMID- 27711202
TI  - Sphingosine 1-Phosphate Activation of EGFR As a Novel Target for Meningitic
      Escherichia coli Penetration of the Blood-Brain Barrier.
AB  - Central nervous system (CNS) infection continues to be an important cause of
      mortality and morbidity, necessitating new approaches for investigating its
      pathogenesis, prevention and therapy. Escherichia coli is the most common Gram
      negative bacillary organism causing meningitis, which develops following
      penetration of the blood-brain barrier (BBB). By chemical library screening, we
      identified epidermal growth factor receptor (EGFR) as a contributor to E. coli
      invasion of the BBB in vitro. Here, we obtained the direct evidence that CNS
      infecting E. coli exploited sphingosine 1-phosphate (S1P) for EGFR activation in
      penetration of the BBB in vitro and in vivo. We found that S1P was upstream of
      EGFR and participated in EGFR activation through S1P receptor as well as through
      S1P-mediated up-regulation of EGFR-related ligand HB-EGF, and blockade of S1P
      function through targeting sphingosine kinase and S1P receptor inhibited EGFR
      activation, and also E. coli invasion of the BBB. We further found that both S1P
      and EGFR activations occurred in response to the same E. coli proteins (OmpA,
      FimH, NlpI), and that S1P and EGFR promoted E. coli invasion of the BBB by
      activating the downstream c-Src. These findings indicate that S1P and EGFR
      represent the novel host targets for meningitic E. coli penetration of the BBB,
      and counteracting such targets provide a novel approach for controlling E. coli
      meningitis in the era of increasing resistance to conventional antibiotics.

PMID- 27711204
TI  - Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.
AB  - Nicotinamide adenine dinucleotide (NAD) is a cofactor involved in a wide range of
      cellular metabolic processes and is a key metabolite required for tumor growth.
      NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM)
      to nicotinamide mononucleotide (NMN), the immediate precursor of NAD, is an
      attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels
      and inhibits tumor growth in vivo. However, there is limited understanding of the
      metabolic response to NAD depletion across cancer cell lines and whether all cell
      lines respond in a uniform manner. To explore this we selected two non-small cell
      lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617
      (A549, NCI-H1334), one that shows intermediate sensitivity (NCI-H441), and one
      that is insensitive (LC-KJ). Even though NAD was reduced in all cell lines there
      was surprising heterogeneity in their metabolic response. Both sensitive cell
      lines reduced glycolysis and levels of di- and tri-nucleotides and modestly
      increased oxidative phosphorylation, but they differed in their ability to combat
      oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549
      cells were unable to activate AMPK as they contain a mutation in LKB1, which
      prevents activation of AMPK. However, A549 cells increased utilization of the
      Pentose Phosphate pathway (PPP) and had lower reactive oxygen species (ROS)
      levels than H1334 cells, indicating that A549 cells are better able to modulate
      an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated
      with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT
      inhibition. Our data reveals that cell lines show heterogeneous response to NAD
      depletion and that the underlying molecular and genetic framework in cells can
      influence the metabolic response to NAMPT inhibition.

PMID- 27711205
TI  - Zoonoses As Ecological Entities: A Case Review of Plague.
AB  - As a zoonosis, Plague is also an ecological entity, a complex system of
      ecological interactions between the pathogen, the hosts, and the spatiotemporal
      variations of its ecosystems. Five reservoir system models have been proposed:
      (i) assemblages of small mammals with different levels of susceptibility and
      roles in the maintenance and amplification of the cycle; (ii) species-specific
      chronic infection models; (ii) flea vectors as the true reservoirs; (iii)
      Telluric Plague, and (iv) a metapopulation arrangement for species with a
      discrete spatial organization, following a source-sink dynamic of extinction and
      recolonization with naive potential hosts. The diversity of the community that
      harbors the reservoir system affects the transmission cycle by predation,
      competition, and dilution effect. Plague has notable environmental constraints,
      depending on altitude (500+ meters), warm and dry climates, and conditions for
      high productivity events for expansion of the transmission cycle. Human impacts
      are altering Plague dynamics by altering landscape and the faunal composition of
      the foci and adjacent areas, usually increasing the presence and number of human
      cases and outbreaks. Climatic change is also affecting the range of its
      occurrence. In the current transitional state of zoonosis as a whole, Plague is
      at risk of becoming a public health problem in poor countries where ecosystem
      erosion, anthropic invasion of new areas, and climate change increase the contact
      of the population with reservoir systems, giving new urgency for ecologic
      research that further details its maintenance in the wild, the spillover events,
      and how it links to human cases.

PMID- 27711206
TI  - Emergence of Epidemic Dengue-1 Virus in the Southern Province of Sri Lanka.
AB  - BACKGROUND: Dengue is a frequent cause of acute febrile illness with an expanding
      global distribution. Since the 1960s, dengue in Sri Lanka has been documented
      primarily along the heavily urbanized western coast with periodic shifting of
      serotypes. Outbreaks from 2005-2008 were attributed to a new clade of DENV-3 and
      more recently to a newly introduced genotype of DENV-1. In 2007, we conducted
      etiologic surveillance of acute febrile illness in the Southern Province and
      confirmed dengue in only 6.3% of febrile patients, with no cases of DENV-1
      identified. To re-evaluate the importance of dengue as an etiology of acute
      febrile illness in this region, we renewed fever surveillance in the Southern
      Province to newly identify and characterize dengue. METHODOLOGY/PRINCIPAL
      FINDINGS: A cross-sectional surveillance study was conducted at the largest
      tertiary care hospital in the Southern Province from 2012-2013. A total of 976
      patients hospitalized with acute undifferentiated fever were enrolled, with 64.3%
      male and 31.4% children. Convalescent blood samples were collected from 877
      (89.6%). Dengue virus isolation, dengue RT-PCR, and paired IgG ELISA were
      performed. Acute dengue was confirmed as the etiology for 388 (39.8%) of 976
      hospitalizations, with most cases (291, 75.0%) confirmed virologically and by
      multiple methods. Among 351 cases of virologically confirmed dengue, 320 (91.2%)
      were due to DENV-1. Acute dengue was associated with self-reported rural
      residence, travel, and months having greatest rainfall. Sequencing of selected
      dengue viruses revealed that sequences were most closely related to those
      described from China and Southeast Asia, not nearby India.
      CONCLUSIONS/SIGNIFICANCE: We describe the first epidemic of DENV-1 in the
      Southern Province of Sri Lanka in a population known to be susceptible to this
      serotype because of prior study. Dengue accounted for 40% of acute febrile
      illnesses in the current study. The emergence of DENV-1 as the foremost serotype
      in this densely populated but agrarian population highlights the changing
      epidemiology of dengue and the need for continued surveillance and prevention.

PMID- 27711208
TI  - Modeled Impacts of Chronic Wasting Disease on White-Tailed Deer in a Semi-Arid
      Environment.
AB  - White-tailed deer are a culturally and economically important game species in
      North America, especially in South Texas. The recent discovery of chronic wasting
      disease (CWD) in captive deer facilities in Texas has increased concern about the
      potential emergence of CWD in free-ranging deer. The concern is exacerbated
      because much of the South Texas region is a semi-arid environment with variable
      rainfall, where precipitation is strongly correlated with fawn recruitment.
      Further, the marginally productive rangelands, in combination with erratic fawn
      recruitment, results in populations that are frequently density-independent, and
      thus sensitive to additive mortality. It is unknown how a deer population in semi
      arid regions would respond to the presence of CWD. We used long-term empirical
      datasets from a lightly harvested (2% annual harvest) population in conjunction
      with 3 prevalence growth rates from CWD afflicted areas (0.26%, 0.83%, and 2.3%
      increases per year) via a multi-stage partially deterministic model to simulate a
      deer population for 25 years under four scenarios: 1) without CWD and without
      harvest, 2) with CWD and without harvest, 3) with CWD and male harvest only, and
      4) with CWD and harvest of both sexes. The modeled populations without CWD and
      without harvest averaged a 1.43% annual increase over 25 years; incorporation of
      2% annual harvest of both sexes resulted in a stable population. The model with
      slowest CWD prevalence rate growth (0.26% annually) without harvest resulted in
      stable populations but the addition of 1% harvest resulted in population
      declines. Further, the male age structure in CWD models became skewed to younger
      age classes. We incorporated fawn:doe ratios from three CWD afflicted areas in
      Wisconsin and Wyoming into the model with 0.26% annual increase in prevalence and
      populations did not begin to decline until ~10%, ~16%, and ~26% of deer were
      harvested annually. Deer populations in variable environments rely on high adult
      survivorship to buffer the low and erratic fawn recruitment rates. The increase
      in additive mortality rates for adults via CWD negatively impacted simulated
      population trends to the extent that hunter opportunity would be greatly reduced.
      Our results improve understanding of the potential influences of CWD on deer
      populations in semi-arid environments with implications for deer managers,
      disease ecologists, and policy makers.

PMID- 27711207
TI  - Genetic Modifiers of White Blood Cell Count, Albuminuria and Glomerular
      Filtration Rate in Children with Sickle Cell Anemia.
AB  - Discovery and validation of genetic variants that influence disease severity in
      children with sickle cell anemia (SCA) could lead to early identification of high
      risk patients, better screening strategies, and intervention with targeted and
      preventive therapy. We hypothesized that newly identified genetic risk factors
      for the general African American population could also impact laboratory
      biomarkers known to contribute to the clinical disease expression of SCA,
      including variants influencing the white blood cell count and the development of
      albuminuria and abnormal glomerular filtration rate. We first investigated
      candidate genetic polymorphisms in well-characterized SCA pediatric cohorts from
      three prospective NHLBI-supported clinical trials: HUSTLE, SWiTCH, and TWiTCH. We
      also performed whole exome sequencing to identify novel genetic variants, using
      both a discovery and a validation cohort. Among candidate genes, DARC rs2814778
      polymorphism regulating Duffy antigen expression had a clear influence with
      significantly increased WBC and neutrophil counts, but did not affect the maximum
      tolerated dose of hydroxyurea therapy. The APOL1 G1 polymorphism, an identified
      risk factor for non-diabetic renal disease, was associated with albuminuria.
      Whole exome sequencing discovered several novel variants that maintained
      significance in the validation cohorts, including ZFHX4 polymorphisms affecting
      both the leukocyte and neutrophil counts, as well as AGGF1, CYP4B1, CUBN, TOR2A,
      PKD1L2, and CD163 variants affecting the glomerular filtration rate. The
      identification of robust, reliable, and reproducible genetic markers for disease
      severity in SCA remains elusive, but new genetic variants provide avenues for
      further validation and investigation.

PMID- 27711209
TI  - The Association between Elevated Levels of Peripheral Serotonin and Its
      Metabolite - 5-Hydroxyindoleacetic Acid and Bone Strength and Metabolism in
      Growing Rats with Mild Experimental Chronic Kidney Disease.
AB  - Chronic kidney disease (CKD) is associated with disturbances in bone strength and
      metabolism. The alterations of the serotonergic system are also observed in CKD.
      We used the 5/6 nephrectomy model of CKD to assess the impact of peripheral
      serotonin and its metabolite- 5-hydroxyindoleacetic acid on bone biomechanical
      properties and metabolism in growing rats. The animals were sacrificed one and
      three months after nephrectomy. Biomechanical properties were determined on two
      different bone types: the cortical bone of the femoral diaphysis using three
      point bending test and the mixed cortico-trabecular bone by the bending test of
      the femoral neck. Biomechanical tests revealed preserved cortical bone strength,
      whereas work to fracture (W) and yield load (Fy) of mixed cortico-trabecular bone
      were significantly lower in CKD compared to controls. Serum activity of alkaline
      phosphatase (ALP), a bone formation marker, and tartrate-resistant acid
      phosphatase (TRACP 5b) reflecting bone resorption, were similar in CKD and
      controls. ALP was associated with lower femoral stiffness and strength, and
      higher displacements and W. TRACP 5b was inversely associated with cortical Fu
      and W. The elevated peripheral serotonergic system in CKD was: inversely
      associated with stiffness but positively related to the displacements and W;
      inversely associated with cortical Fy but positively correlated with this
      parameter in cortico-trabecular bone; inversely associated with ALP in controls
      but positively correlated with this biomarker in CKD animals. In conclusion, this
      study demonstrates the distinct effect of mild degree of CKD on bone strength in
      rapidly growing rats. The impaired renal function affects the peripheral
      serotonin metabolism, which in turn may influence the strength and metabolism of
      bones in these rats. This relationship seems to be beneficial on the
      biomechanical properties of the cortico-trabecular bone, whereas the cortical
      bone strength can be potentially reduced.

PMID- 27711211
TI  - Correlates of Unwanted Births in Bangladesh: A Study through Path Analysis.
AB  - BACKGROUND: Unwanted birth is an important public health concern due to its
      negative association with adverse outcomes of mothers and children as well as
      socioeconomic development of a country. Although a number of studies have been
      investigated the determinants of unwanted births through logistic regression
      analysis, an extensive assessment using path model is lacking. In the current
      study, we applied path analysis to know the important covariates for unwanted
      births in Bangladesh. METHODS: The study used data extracted from Bangladesh
      Demographic and Health Survey (BDHS) 2011. It considered sub-sample consisted of
      7,972 women who had given most recent births five years preceding the date of
      interview or who were currently pregnant at survey time. Correlation analysis was
      used to find out the significant association with unwanted births. This study
      provided the factors affecting unwanted births in Bangladesh. The path model was
      used to determine the direct, indirect and total effects of socio-demographic
      factors on unwanted births. RESULTS: The result exhibited that more than one
      tenth of the recent births were unwanted in Bangladesh. The differentials of
      unwanted births were women's age, education, age at marriage, religion,
      socioeconomic status, exposure of mass-media and use of family planning. In
      correlation analysis, it showed that unwanted births were positively correlated
      with women age and place of residence and these relationships were significant.
      On the contrary, unwanted births were inversely significantly correlated with
      education and social status. The total effects of endogenous variables such as
      women age, place of residence and use of family planning methods had favorable
      effect on unwanted births. CONCLUSION: Policymakers and program planners need to
      design programs and services carefully to reduce unwanted births in Bangladesh,
      especially, service should focus on helping those groups of women who were
      identified in the analysis as being at increased risks of unwanted births- older
      women, illiterate, low socioeconomic status, early age at marriage and rural poor
      susceptible women.

PMID- 27711210
TI  - Signaling of Prostaglandin E Receptors, EP3 and EP4 Facilitates Wound Healing and
      Lymphangiogenesis with Enhanced Recruitment of M2 Macrophages in Mice.
AB  - Lymphangiogenesis plays an important role in homeostasis, metabolism, and
      immunity, and also occurs during wound-healing. Here, we examined the roles of
      prostaglandin E2 (PGE2) receptor (EP) signaling in enhancement of
      lymphangiogenesis in wound healing processes. The hole-punch was made in the ears
      of male C57BL/6 mice using a metal ear punch. Healing process and
      lymphangiogenesis together with macrophage recruitment were analyzed in EP
      knockout mice. Lymphangiogenesis was up-regulated in the granulation tissues at
      the margins of punched-hole wounds in mouse ears, and this increase was
      accompanied by increased expression levels of COX-2 and microsomal prostaglandin
      E synthase-1. Administration of celecoxib, a COX-2 inhibitor, suppressed
      lymphangiogenesis in the granulation tissues and reduced the induction of the pro
      lymphangiogenic factors, vascular endothelial growth factor (VEGF) -C and VEGF-D.
      Topical applications of selective EP receptor agonists enhanced the expressions
      of lymphatic vessel endothelial hyaluronan receptor-1 and VEGF receptor-3. The
      wound-healing processes and recruitment of CD11b-positive macrophages, which
      produced VEGF-C and VEGF-D, were suppressed under COX-2 inhibition. Mice lacking
      either EP3 or EP4 exhibited reduced wound-healing, lymphangiogenesis and
      recruitment of M2 macrophages, compared with wild type mice. Proliferation of
      cultured human lymphatic endothelial cells was not detected under PGE2
      stimulation. Lymphangiogenesis and recruitment of M2 macrophages that produced
      VEGF-C/D were suppressed in mice treated with a COX-2 inhibitor or lacking either
      EP3 or EP4 during wound healing. COX-2 and EP3/EP4 signaling may be novel targets
      to control lymphangiogenesis in vivo.

PMID- 27711212
TI  - Fitting HIV Prevalence 1981 Onwards for Three Indian States Using the Goals Model
      and the Estimation and Projection Package.
AB  - Models are designed to provide evidence for strategic program planning by
      examining the impact of different interventions on projected HIV incidence. We
      employed the Goals Model to fit the HIV epidemic curves in Andhra Pradesh,
      Maharashtra and Tamil Nadu states of India where HIV epidemic is considered to
      have matured and in a declining phase. Input data in the Goals Model consisted of
      demographic, epidemiological, transmission-related and risk group wise behavioral
      parameters. The HIV prevalence curves generated in the Goals Model for each risk
      group in the three states were compared with the epidemic curves generated by the
      Estimation and Projection Package (EPP) that the national program is routinely
      using. In all the three states, the HIV prevalence trends for high-risk
      populations simulated by the Goals Model matched well with those derived using
      state-level HIV surveillance data in the EPP. However, trends for the low- and
      medium-risk populations differed between the two models. This highlights the need
      to generate more representative and robust data in these sub-populations and
      consider some structural changes in the modeling equation and parameters in the
      Goals Model to effectively use it to assess the impact of future strategies of
      HIV control in various sub-populations in India at the sub-national level.

PMID- 27711213
TI  - Determinants of Attitude toward the Public Health Spending and Its Relationship
      with Voting Behavior in the 2012 South Korean Presidential Election.
AB  - This study aimed to identify the factors influencing South Korean voters'
      attitudes towards increasing public expenditure on health and to identify whether
      the issue of healthcare expenditure influenced candidate choice in the 2012
      Korean presidential election. The study used the data from a survey conducted by
      the Institute of Korean Politics at Seoul National University immediately
      following the 2012 presidential election. The survey was completed by a
      nationwide sample of 1,200 people aged 19 or over using a face-to-face interview
      method and proportional quota sampling based on sex, age, and region. About 44.3%
      of respondents had a positive attitude toward increasing public health
      expenditure. There was no significant difference by the candidate they supported
      (conservative Park Geun-hye or liberal Moon Jae-in). In particular, even 44.9% of
      conservative supporters agreed with more spending. Politically neutral
      respondents (OR = 1.76, 90% CI 1.22-2.54) and strong conservative party
      supporters (OR = 1.53, 90% CI 1.05-2.25) were more likely to support public
      health expenditure increase compared to strong liberal party supporters. Also,
      respondents who believed that the economic gap in the country was widening were
      1.91 times more likely to support an increase in public health expenditures.
      However, the issue of health expenditure had no influence on voters' choice of
      presidential candidates, and in particular no negative effect of choice of the
      ruling (conservative) party's candidate. Our results should be interpreted with
      care; one possible reason for this lack of effect might be that constituents
      voted along partisan lines regardless of their attitude to the welfare issue;
      another possible explanation might be the success of the "left click strategy" of
      the conservative party. That is, the conservatives did not reject economic
      democratization or social welfare expansion. Further research should be done to
      explain why attitudes to health spending did not directly affect choice of
      candidate.

PMID- 27711214
TI  - Progressive Dystrophic Pathology in Diaphragm and Impairment of Cardiac Function
      in FKRP P448L Mutant Mice.
AB  - Mutations in the gene for fukutin-related protein represent a subset of muscular
      dystrophies known as dystroglycanopathies characterized by loss of functionally
      glycosylated-alpha-dystroglycan and a wide range of dystrophic phenotypes. Mice
      generated by our lab containing the P448L mutation in the fukutin-related protein
      gene demonstrate the dystrophic phenotype similar to that of LGMD2I. Here we
      examined the morphology of the heart and diaphragm, focusing on pathology of
      diaphragm and cardiac function of the mutant mice for up to 12 months. Both
      diaphragm and heart lack clear expression of functionally-glycosylated-alpha
      dystroglycan throughout the observed period. The diaphragm undergoes progressive
      deterioration in histology with increasing amount of centranucleation and
      inflammation. Large areas of mononuclear cell infiltration and fibrosis of up to
      60% of tissue area were detected as early as 6 months of age. Despite a less
      severe morphology with only patches of mononuclear cell infiltration and fibrosis
      of ~5% by 12 months of age in the heart, cardiac function is clearly affected.
      High frequency ultrasound reveals a smaller heart size up to 10 months of age.
      There are significant increases in myocardial thickness and decrease in cardiac
      output through 12 months. Dysfunction in the heart represents a key marker for
      evaluating experimental therapies aimed at cardiac muscle.

PMID- 27711215
TI  - Heparanase Overexpression Reduces Hepcidin Expression, Affects Iron Homeostasis
      and Alters the Response to Inflammation.
AB  - Hepcidin is the key regulator of systemic iron availability that acts by
      controlling the degradation of the iron exporter ferroportin. It is expressed
      mainly in the liver and regulated by iron, inflammation, erythropoiesis and
      hypoxia. The various agents that control its expression act mainly via the
      BMP6/SMAD signaling pathway. Among them are exogenous heparins, which are strong
      hepcidin repressors with a mechanism of action not fully understood but that may
      involve the competition with the structurally similar endogenous Heparan Sulfates
      (HS). To verify this hypothesis, we analyzed how the overexpression of
      heparanase, the HS degrading enzyme, modified hepcidin expression and iron
      homeostasis in hepatic cell lines and in transgenic mice. The results showed that
      transient and stable overexpression of heparanase in HepG2 cells caused a
      reduction of hepcidin expression and of SMAD5 phosphorylation. Interestingly, the
      clones showed also altered level of TfR1 and ferritin, indices of a modified iron
      homeostasis. The heparanase transgenic mice showed a low level of liver hepcidin,
      an increase of serum and liver iron with a decrease in spleen iron content. The
      hepcidin expression remained surprisingly low even after treatment with the
      inflammatory LPS. The finding that modification of HS structure mediated by
      heparanase overexpression affects hepcidin expression and iron homeostasis
      supports the hypothesis that HS participate in the mechanisms controlling
      hepcidin expression.

PMID- 27711216
TI  - A Link No Longer Missing: New Evidence for the Cetotheriid Affinities of Caperea.
AB  - The origins of the enigmatic pygmy right whale Caperea marginata, the only living
      member of its subfamily (Neobalaeninae), are an outstanding mystery of cetacean
      evolution. Its strikingly disparate morphology sets Caperea apart from all other
      whales, and has turned it into a wildcard taxon that holds the key to
      understanding modern baleen whale diversity. Morphological cladistics generally
      ally this species with right whales, whereas molecular analyses consistently
      cluster it with rorquals and grey whales (Balaenopteroidea). A recent study
      potentially resolved this conflict by proposing that Caperea belongs with the
      otherwise extinct Cetotheriidae, but has been strongly criticised on
      morphological grounds. Evidence from the neobalaenine fossil record could
      potentially give direct insights into morphological transitions, but is currently
      limited to just a single species: the Late Miocene Miocaperea pulchra, from Peru.
      We show that Miocaperea has a highly unusual morphology of the auditory region,
      resulting from a-presumably feeding-related-strengthening of the articulation of
      the hyoid apparatus with the skull. This distinctive arrangement is otherwise
      only found in the extinct Cetotheriidae, which makes Miocaperea a "missing link"
      that demonstrates the origin of pygmy right whales from cetotheriids, and
      confirms the latter's resurrection from the dead.

PMID- 27711218
TI  - Behavioural and Psychiatric Phenotypes in Men and Boys with X-Linked Ichthyosis:
      Evidence from a Worldwide Online Survey.
AB  - BACKGROUND: X-linked ichthyosis (XLI) is a rare dermatological condition arising
      from deficiency for the enzyme steroid sulfatase (STS). Preliminary evidence in
      boys with XLI, and animal model studies, suggests that individuals lacking STS
      are at increased risk of developmental disorders and associated traits. However,
      the behavioural profile of children with XLI is poorly-characterised, and the
      behavioural profile of adults with XLI has not yet been documented at all.
      MATERIALS AND METHODS: Using an online survey, advertised worldwide, we collected
      detailed self- or parent-reported information on behaviour in adult (n = 58) and
      younger (<=18yrs, n = 24) males with XLI for comparison to data from their non
      affected brothers, and age/gender-matched previously-published normative data.
      The survey comprised demographic and background information (including any prior
      clinical diagnoses) and validated questionnaires assaying phenotypes of
      particular interest (Adult ADHD Self-Report Scale v1.1, Barrett Impulsiveness
      Scale-11, adult and adolescent Autism Quotient, Kessler Psychological Distress
      Scales, and Disruptive Behaviour Disorder Rating Scale). RESULTS: Individuals
      with XLI generally exhibited normal sensory function. Boys with XLI were at
      increased risk of developmental disorder, whilst adults with the condition were
      at increased risk of both developmental and mood disorders. Both adult and
      younger XLI groups scored significantly more highly than male general population
      norms on measures of inattention, impulsivity, autism-related traits,
      psychological distress and disruptive behavioural traits. CONCLUSIONS: These
      findings indicate that both adult and younger males with XLI exhibit personality
      profiles that are distinct from those of males within the general population, and
      suggest that individuals with XLI may be at heightened risk of psychopathology.
      The data are consistent with the notion that STS is important in neurodevelopment
      and ongoing brain function, and with previous work suggesting high rates of
      developmental disorders in boys with XLI. Our results suggest that individuals
      with XLI may require medical care from multidisciplinary teams, and should help
      to inform genetic counselling for the condition.

PMID- 27711217
TI  - Multi-Functional OCT Enables Longitudinal Study of Retinal Changes in a VLDLR
      Knockout Mouse Model.
AB  - We present a multi-functional optical coherence tomography (OCT) imaging approach
      to study retinal changes in the very-low-density-lipoprotein-receptor (VLDLR)
      knockout mouse model with a threefold contrast. In the retinas of VLDLR knockout
      mice spontaneous retinal-chorodoidal neovascularizations form, having an
      appearance similar to choroidal and retinal neovascularizations (CNV and RNV) in
      neovascular age-related macular degeneration (AMD) or retinal angiomatous
      proliferation (RAP). For this longitudinal study, the mice were imaged every 4 to
      6 weeks starting with an age of 4 weeks and following up to the age of 11 months.
      Significant retinal changes were identified by the multi-functional imaging
      approach offering a threefold contrast: reflectivity, polarization sensitivity
      (PS) and motion contrast based OCT angiography (OCTA). By use of this intrinsic
      contrast, the long-term development of neovascularizations was studied and
      associated processes, such as the migration of melanin pigments or retinal
      choroidal anastomosis, were assessed in vivo. Furthermore, the in vivo imaging
      results were validated with histological sections at the endpoint of the
      experiment. Multi-functional OCT proves as a powerful tool for longitudinal
      retinal studies in preclinical research of ophthalmic diseases. Intrinsic
      contrast offered by the functional extensions of OCT might help to describe
      regulative processes in genetic animal models and potentially deepen the
      understanding of the pathogenesis of retinal diseases such as wet AMD.

PMID- 27711219
TI  - Assessing Basal and Acute Autophagic Responses in the Adult Drosophila Nervous
      System: The Impact of Gender, Genetics and Diet on Endogenous Pathway Profiles.
AB  - The autophagy pathway is critical for the long-term homeostasis of cells and
      adult organisms and is often activated during periods of stress. Reduced pathway
      efficacy plays a central role in several progressive neurological disorders that
      are associated with the accumulation of cytotoxic peptides and protein
      aggregates. Previous studies have shown that genetic and transgenic alterations
      to the autophagy pathway impacts longevity and neural aggregate profiles of adult
      Drosophila. In this study, we have identified methods to measure the acute in
      vivo induction of the autophagy pathway in the adult fly CNS. Our findings
      indicate that the genotype, age, and gender of adult flies can influence pathway
      responses. Further, we demonstrate that middle-aged male flies exposed to
      intermittent fasting (IF) had improved neuronal autophagic profiles. IF-treated
      flies also had lower neural aggregate profiles, maintained more youthful
      behaviors and longer lifespans, when compared to ad libitum controls. In summary,
      we present methodology to detect dynamic in vivo changes that occur to the
      autophagic profiles in the adult Drosophila CNS and that a novel IF-treatment
      protocol improves pathway response in the aging nervous system.

PMID- 27711221
TI  - Enlargement of the Axial Length and Altered Ultrastructural Features of the
      Sclera in a Mutant Lumican Transgenic Mouse Model.
AB  - Lumican (LUM) is a candidate gene for myopia in the MYP3 locus. In this study, a
      mutant lumican (L199P) transgenic mouse model was established to investigate the
      axial length changes and ultrastructural features of the sclera. The mouse model
      was established by pronuclear microinjection. Transgenic mice and wild-type B6
      mice were killed at eight weeks of age. Gene expression levels of LUM and
      collagen type I (COL1) in the sclera were analyzed by quantitative real-time
      polymerase chain reaction (qPCR), and the protein levels were assessed by Western
      blot analysis. Ocular axial lengths were measured on the enucleated whole eye
      under a dissecting microscope. Ultrastructural features of collagen fibrils in
      the sclera were examined with transmission electron microscopy (TEM). Lumican and
      collagen type I were both elevated at the transcriptional and protein levels. The
      mean axial length of eyes in the transgenic mice was significantly longer than
      that in the wild-type mice (3,231.0 +/- 11.2 MUm (transgenic group) vs 3,199.7 +/
      11.1 MUm (controls), p<0.05 =). Some ultrastructural changes were observed in
      the sclera of the transgenic mice under TEM, such as evident lamellar
      disorganizations and abnormal inter-fibril spacing. The average collagen fibril
      diameter was smaller than that in their wild-type counterparts. These results
      indicate that the ectopic mutant lumican (L199P) may induce enlargement of axial
      lengths and abnormal structures and distributions of collagen fibrils in mouse
      sclera. This transgenic mouse model can be used for the mechanistic study of
      myopia.

PMID- 27711220
TI  - Acute Infectious Gastroenteritis Potentiates a Crohn's Disease Pathobiont to Fuel
      Ongoing Inflammation in the Post-Infectious Period.
AB  - Crohn's disease (CD) is a chronic inflammatory condition of diverse etiology.
      Exposure to foodborne pathogens causing acute gastroenteritis produces a long
      term risk of CD well into the post-infectious period but the mechanistic basis
      for this ongoing relationship to disease onset is unknown. We developed two novel
      models to study the comorbidity of acute gastroenteritis caused by Salmonella
      Typhimurium or Citrobacter rodentium in mice colonized with adherent-invasive
      Escherichia coli (AIEC), a bacterial pathobiont linked to CD. Here, we show that
      disease activity in the post-infectious period after gastroenteritis is driven by
      the tissue-associated expansion of the resident AIEC pathobiont, with an
      attendant increase in immunopathology, barrier defects, and delays in mucosal
      restitution following pathogen clearance. These features required AIEC resistance
      to host defense peptides and a fulminant inflammatory response to the enteric
      pathogen. Our results suggest that individuals colonized by AIEC at the time of
      acute infectious gastroenteritis may be at greater risk for CD onset.
      Importantly, our data identify AIEC as a tractable disease modifier, a finding
      that could be exploited in the development of therapeutic interventions following
      infectious gastroenteritis in at-risk individuals.

PMID- 27711222
TI  - Association between Traffic Air Pollution and Reduced Forced Vital Capacity: A
      Study Using Personal Monitors for Outdoor Workers.
AB  - BACKGROUND: The effects of outdoor air pollution on lung function in adults are
      still controversial. OBJECTIVE: Evaluate the effects of exposure to different
      levels of traffic-generated PM2.5 on workers' lung functions in Sao Paulo,
      Brazil. METHODS: To cover a wide range of exposures, 101 non-smoking workers from
      three occupations (taxi drivers, traffic controllers, and forest rangers) were
      selected for the study. After clinical evaluation, the participants were
      scheduled to attend four consecutive weekly visits in which they received a 24
      hour personal PM2.5 sampler and had lung function tests measured on the following
      day. The association between the spirometric variables and the averaged PM2.5
      levels was assessed using robust regression models adjusted for age, waist
      circumference, time at the job, daily work hours, diabetes or hypertension and
      former smoking habits. RESULTS: Relative to workers in the lowest exposed group
      (all measures < 25 MUg/m3), those with the highest level of exposure (all
      measures > 39.6 MUg/m3) showed a reduction of predicted FVC (-12.2%; CI 95%: [
      20.0% to -4.4%]), a marginal reduction of predicted FEV1 (-9.1%; CI 95%: [-19.1%
      to 0.9%]) and an increase of predicted FEF25-75%/FVC (14.9%; CI 95%: [2.9% to
      26.8%]) without changes of FEV1/FVC. CONCLUSIONS: Exposure to vehicular traffic
      air pollution is associated with a small but significant reduction of FVC without
      a reduction of FEV1/FVC.

PMID- 27711223
TI  - The Bacterial Mfd Protein Prevents DNA Damage Induced by the Host Nitrogen Immune
      Response in a NER-Independent but RecBC-Dependent Pathway.
AB  - Production of reactive nitrogen species is an important component of the host
      immune defence against bacteria. Here, we show that the bacterial protein Mfd
      (Mutation frequency decline), a highly conserved and ubiquitous bacterial protein
      involved in DNA repair, confers bacterial resistance to the eukaryotic nitrogen
      response produced by macrophage cells and during mice infection. In addition, we
      show that RecBC is also necessary to survive this stress. The inactivation of
      recBC and mfd genes is epistatic showing that Mfd follows the RecBC repair
      pathway to protect the bacteria against the genotoxic effect of nitrite.
      Surprisingly given the role of Mfd in transcription-coupled repair, UvrA is not
      necessary to survive the nitrite response. Taken together, our data reveal that
      during the eukaryotic nitrogen response, Mfd is required to maintain bacterial
      genome integrity in a NER-independent but RecBC-dependent pathway.

PMID- 27711224
TI  - Benzodiazepine Use During Hospitalization: Automated Identification of Potential
      Medication Errors and Systematic Assessment of Preventable Adverse Events.
AB  - OBJECTIVE: Benzodiazepines and "Z-drug" GABA-receptor modulators (BDZ) are among
      the most frequently used drugs in hospitals. Adverse drug events (ADE) associated
      with BDZ can be the result of preventable medication errors (ME) related to
      dosing, drug interactions and comorbidities. The present study evaluated
      inpatient use of BDZ and related ME and ADE. METHODS: We conducted an
      observational study within a pharmacoepidemiological database derived from the
      clinical information system of a tertiary care hospital. We developed algorithms
      that identified dosing errors and interacting comedication for all administered
      BDZ. Associated ADE and risk factors were validated in medical records. RESULTS:
      Among 53,081 patients contributing 495,813 patient-days BDZ were administered to
      25,626 patients (48.3%) on 115,150 patient-days (23.2%). We identified 3,372
      patient-days (2.9%) with comedication that inhibits BDZ metabolism, and 1,197
      (1.0%) with lorazepam administration in severe renal impairment. After validation
      we classified 134, 56, 12, and 3 cases involving lorazepam, zolpidem, midazolam
      and triazolam, respectively, as clinically relevant ME. Among those there were 23
      cases with associated adverse drug events, including severe CNS-depression, falls
      with subsequent injuries and severe dyspnea. Causality for BDZ was formally
      assessed as 'possible' or 'probable' in 20 of those cases. Four cases with ME and
      associated severe ADE required administration of the BDZ antagonist flumazenil.
      CONCLUSIONS: BDZ use was remarkably high in the studied setting, frequently
      involved potential ME related to dosing, co-medication and comorbidities, and
      rarely cases with associated ADE. We propose the implementation of automated ME
      screening and validation for the prevention of BDZ-related ADE.

PMID- 27711225
TI  - Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify
      Primary Prostate Tumors that Metastasize to the Bone.
AB  - BACKGROUND: Benign human prostate tubule-initiating cells (TIC) and aggressive
      prostate cancer display common traits, including tolerance of low androgen
      levels, resistance to apoptosis, and microenvironment interactions that drive
      epithelial budding and outgrowth. TIC can be distinguished from epithelial and
      stromal cells that comprise prostate tissue via cell sorting based upon Epcam,
      CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess
      a similar antigenic profile to adult TIC and are capable of inducing tubule
      formation. To identify the TIC niche in human prostate tissue, differential
      keratin (KRT) expression was evaluated. RESULTS: Gene expression data generated
      from Affymetrix Gene Chip human U133 Plus 2.0 array of sorted adult and fetal
      epithelial cells revealed KRT13 to be significantly enriched in FC and TIC
      compared to basal cells (BC) and luminal cells (LC) (p<0.001). Enriched KRT13
      expression was confirmed by RT-PCR and cytospin immunostaining.
      Immunohistochemical analysis of KRT13 expression revealed rare KRT13+ epithelia
      throughout prostatic ducts/acini in adult tissue specimens and differentiated
      tubules in 24-week recombinant grafts, In contrast, abundant KRT13 expression was
      observed in developing ducts/acini in fetal prostate and cord-like structures
      composing 8-week recombinant grafts. Immunostaining of a prostate tissue
      microarray revealed KRT13+ tumor foci in approximately 9% of cases, and this
      subset displayed significantly shorter time to recurrence (p = 0.031), metastases
      (p = 0.032), and decreased overall survival (p = 0.004). Diagnostic prostate
      needle biopsies (PNBX) from untreated patients with concurrent bone metastases
      (clinical stage M1) displayed KRT13+ tumor foci, as did bone metastatic foci.
      CONCLUSIONS: The expression profile of KRT13 in benign fetal and adult prostate
      tissue and in recombinant grafts, as well as the frequency of KRT13 expression in
      primary and metastatic prostate cancer indicates that it may be a marker of a
      stem/progenitor-like cell state that is co-opted in aggressive tumor cells. KRT13
      is enriched in benign stem-like cells that display androgen-resistance, apoptosis
      resistance, and branching morphogenesis properties. Collectively our data
      demonstrate that KRT13 expression is associated with poor prognosis at multiple
      stages of disease progression and may represent an important biomarker of adverse
      outcome in patients with prostate cancer.

PMID- 27711226
TI  - Placental Growth Factor Is Secreted by the Human Endometrium and Has Potential
      Important Functions during Embryo Development and Implantation.
AB  - Embryo implantation requires synchronized dialogue between the receptive
      endometrium and activated blastocyst via locally produced soluble mediators.
      During the mid-secretory (MS) phase of the menstrual cycle, increased glandular
      secretion into the uterine lumen provides important mediators that modulate the
      endometrium and support the conceptus during implantation. Previously we
      demonstrated the importance of vascular endothelial growth factor (VEGF) in the
      human uterus, particularly with respect to embryo implantation. In the current
      study, proteomic analysis of human uterine lavage fluid identified the presence
      of placental growth factor (PlGF) a homolog of VEGF, that binds the VEGF receptor
      1 (VEGFR1). Analysis of immunostaining for PlGF in human endometrial tissue
      across the menstrual cycle (from both fertile and infertile women) revealed PlGF
      was predominantly localised to glandular and luminal epithelial cells, with
      staining in the decidualising stromal cells surrounding the maternal spiral
      arteries in the secretory phase of the menstrual cycle. Immunoreactive PlGF was
      also detected in subpopulations of endometrial leukocytes. Functional studies
      demonstrated that culturing mouse embryos with recombinant human (rh)PlGF
      enhanced blastocyst cell number and outgrowth. Furthermore, treatment of human
      endometrial epithelial cells (EEC) with rhPlGF enhanced EEC adhesion. Taken
      together, these data demonstrate that PlGF is abundant in the human endometrium,
      and secreted into the uterine lumen where it mediates functional changes in
      cellular adhesion with important roles in implantation.

PMID- 27711227
TI  - Systemic Administration of Allogeneic Mesenchymal Stem Cells Does Not Halt
      Osteoporotic Bone Loss in Ovariectomized Rats.
AB  - Mesenchymal stem cells (MSCs) have innate ability to self-renew and
      immunosuppressive functions, and differentiate into various cell types. They have
      become a promising cell source for treating many diseases, particular for bone
      regeneration. Osteoporosis is a common metabolic bone disorder with elevated
      systemic inflammation which in turn triggers enhanced bone loss. We hypothesize
      that systemic infusion of MSCs may suppress the elevated inflammation in the
      osteoporotic subjects and slow down bone loss. The current project was to address
      the following two questions: (1) Will a single dose systemic administration of
      allogenic MSCs have any effect on osteoporotic bone loss? (2) Will multiple
      administration of allogenic MSCs from single or multiple donors have similar
      effect on osteoporotic bone loss? 18 ovariectomized (OVX) rats were assigned into
      3 groups: the PBS control group, MSCs group 1 (receiving 2x106 GFP-MSCs at Day
      10, 46, 91 from the same donor following OVX) and MSCs group 2 (receiving 2x106
      GFP-MSCs from three different donors at Day 10, 46, 91). Examinations included
      Micro-CT, serum analysis, mechanical testing, immunofluorescence staining and
      bone histomorphometry analysis. Results showed that BV/TV at Day 90, 135, BMD of
      TV and trabecular number at Day 135 in the PBS group were significantly higher
      than those in the MSCs group 2, whereas trabecular spacing at Day 90, 135 was
      significantly smaller than that in MSCs group 2. Mechanical testing data didn't
      show significant difference among the three groups. In addition, the ELISA assay
      showed that level of Rantes in serum in MSCs group 2 was significantly higher
      than that of the PBS group, whereas IL-6 and IL-10 were significantly lower than
      those of the PBS group. Bone histomorphometry analysis showed that Oc.S/BS and
      Oc.N/BS in the PBS group were significant lower than those in MSCs group 2;
      Ob.S/BS and Ob.N/BS did not show significant difference among the three groups.
      The current study demonstrated that systemic administration of allogenic MSCs had
      no obvious effect on osteoporotic bone loss in OVX rats when using the cells from
      the same donor; and repeated injection of allogeneic MSCs from different donors
      might promote bone loss in OVX rats. These findings indicate that despite
      allogenic MSCs systemic infusion is safe, their administration alone may not be
      an effective mean for preventing osteoporotic bone loss.

PMID- 27711228
TI  - DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on
      Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune
      Responses without Control of Re-Emergent Virus.
AB  - : GV-TH-01, a Phase 1 open-label trial of a DNA prime-Modified Vaccinia Ankara
      (MVA) boost vaccine (GOVX-B11), was undertaken in HIV infected participants on
      antiretroviral treatment (ART) to evaluate safety and vaccine-elicited T cell
      responses, and explore the ability of elicited CD8+ T cells to control viral
      rebound during analytical treatment interruption (TI). Nine men who began
      antiretroviral therapy (ART) within 18 months of seroconversion and had sustained
      plasma HIV-1 RNA <50 copies/mL for at least 6 months were enrolled. Median age
      was 38 years, median pre-ART HIV-1 RNA was 140,000 copies/ml and mean baseline
      CD4 count was 755/MUl. Two DNA, followed by 2 MVA, inoculations were given 8
      weeks apart. Eight subjects completed all vaccinations and TI. Clinical and
      laboratory adverse events were generally mild, with no serious or grade 4 events.
      Only reactogenicity events were considered related to study drug. No treatment
      emergent viral resistance was seen. The vaccinations did not reduce viral
      reservoirs and virus re-emerged in all participants during TI, with a median time
      to re-emergence of 4 weeks. Eight of 9 participants had CD8+ T cells that could
      be stimulated by vaccine-matched Gag peptides prior to vaccination. Vaccinations
      boosted these responses as well as eliciting previously undetected CD8+
      responses. Elicited T cells did not display signs of exhaustion. During TI,
      temporal patterns of viral re-emergence and Gag-specific CD8+ T cell expansion
      suggested that vaccine-specific CD8+ T cells had been stimulated by re-emergent
      virus in only 2 of 8 participants. In these 2, transient decreases in viremia
      were associated with Gag selection in known CD8+ T cell epitopes. We hypothesize
      that escape mutations, already archived in the viral reservoir, plus a poor
      ability of CD8+ T cells to traffic to and control virus at sites of re-emergence,
      limited the therapeutic efficacy of the DNA/MVA vaccine. TRIAL REGISTRATION:
      clinicaltrials.gov NCT01378156.

PMID- 27711229
TI  - Cell-Free Phospholipid Biosynthesis by Gene-Encoded Enzymes Reconstituted in
      Liposomes.
AB  - The goal of bottom-up synthetic biology culminates in the assembly of an entire
      cell from separate biological building blocks. One major challenge resides in the
      in vitro production and implementation of complex genetic and metabolic pathways
      that can support essential cellular functions. Here, we show that phospholipid
      biosynthesis, a multiple-step process involved in cell membrane homeostasis, can
      be reconstituted starting from the genes encoding for all necessary proteins. A
      total of eight E. coli enzymes for acyl transfer and headgroup modifications were
      produced in a cell-free gene expression system and were co-translationally
      reconstituted in liposomes. Acyl-coenzyme A and glycerol-3-phosphate were used as
      canonical precursors to generate a variety of important bacterial lipids.
      Moreover, this study demonstrates that two-step acyl transfer can occur from
      enzymes synthesized inside vesicles. Besides clear implications for growth and
      potentially division of a synthetic cell, we postulate that gene-based lipid
      biosynthesis can become instrumental for ex vivo and protein purification-free
      production of natural and non-natural lipids.

PMID- 27711231
TI  - Comprehensive Retinal Image Analysis for Aggressive Posterior Retinopathy of
      Prematurity.
AB  - Computer aided analysis plays a nontrivial role in assisting the diagnosis of
      various eye pathologies. In this paper, we propose a framework to help diagnose
      the presence of Aggressive Posterior Retinopathy Of Prematurity (APROP), a
      pathology that is characterised by rapid onset and increased tortuosity of blood
      vessels close to the optic disc (OD). We quantify vessel characteristics that are
      of clinical relevance to APROP such as tortuosity and the extent of branching
      i.e., vessel segment count in the defined diagnostic region. We have adapted
      three vessel segmentation techniques: matched filter response, scale space theory
      and morphology with local entropy based thresholding. The proposed feature set
      equips us to build a linear discriminant classifier to discriminate APROP images
      from clinically healthy images. We have studied 36 images from 21 APROP subjects
      against a control group of 15 clinically healthy age matched infants. All
      subjects are age matched ranging from 33-40 weeks of post menstrual age.
      Experimental results show that we attain 100% recall and 95.45% precision, when
      the vessel network obtained from morphology is used for feature extraction.

PMID- 27711230
TI  - The Role of Hepatitis C Virus Core Antigen Testing in the Era of Direct Acting
      Antiviral Therapies: What We Can Learn from the Protease Inhibitors.
AB  - Direct-acting antiviral (DAA) therapies have revolutionised the treatment of
      hepatitis C virus (HCV). The financial cost of DAAs however is significant, and
      first generation protease inhibitors (PIs) also require frequent monitoring of
      viral RNA levels to guide treatment. In this context, we examined the relevance
      of HCV antigen testing to evaluate the potential role in monitoring virological
      response to HCV antiviral treatment with the PI-based triple therapies,
      telaprevir (TVR) and boceprevir (BOC). Chronic HCV-infected individuals (n = 152)
      enrolled in the Irish Hepatitis C Outcomes Research Network (ICORN) study were
      prospectively analysed for baseline markers and the early viral kinetics
      associated with SVR. The sustained virological response (SVR) rates in the cohort
      receiving TVR and BOC were 87.3% and 73.8%, respectively. Baseline factors
      associated with successful outcome in TVR therapy were age (P = 0.0098), IFNL3
      genotype (P = 0.0330) and viral load (P = 0.0456). RNA level at week 4 (P =
      0.0068) and viral antigen negativity at week 2 (P = 0.0359) were predictive of
      SVR for TVR-based therapy. In BOC therapy, prior interferon treatment (P =
      0.0209) and IFNL3 genotype (P = 0.0410) were baseline predictors of SVR. Evidence
      of viraemia based either on viral RNA or antigen at week 4 predicted SVR in these
      patients. Our data showed that rapid decline of HCV antigen to negative level at
      week 2 in TVR treatment and <0.96 log fmol/l in BOC treatment after commencement
      of PI triple therapy were associated with SVR. HCV antigen measurement should be
      considered as a potential alternative for monitoring treatment response during
      DAA-based regimens.

PMID- 27711232
TI  - Self-Contained Statistical Analysis of Gene Sets.
AB  - Microarrays are a powerful tool for studying differential gene expression.
      However, lists of many differentially expressed genes are often generated, and
      unraveling meaningful biological processes from the lists can be challenging. For
      this reason, investigators have sought to quantify the statistical probability of
      compiled gene sets rather than individual genes. The gene sets typically are
      organized around a biological theme or pathway. We compute correlations between
      different gene set tests and elect to use Fisher's self-contained method for gene
      set analysis. We improve Fisher's differential expression analysis of a gene set
      by limiting the p-value of an individual gene within the gene set to prevent a
      small percentage of genes from determining the statistical significance of the
      entire set. In addition, we also compute dependencies among genes within the set
      to determine which genes are statistically linked. The method is applied to T-ALL
      (T-lineage Acute Lymphoblastic Leukemia) to identify differentially expressed
      gene sets between T-ALL and normal patients and T-ALL and AML (Acute Myeloid
      Leukemia) patients.

PMID- 27711233
TI  - Sterol Regulatory Element Binding Protein (Srb1) Is Required for Hypoxic
      Adaptation and Virulence in the Dimorphic Fungus Histoplasma capsulatum.
AB  - The Histoplasma capsulatum sterol regulatory element binding protein (SREBP),
      Srb1 is a member of the basic helix-loop-helix (bHLH), leucine zipper DNA binding
      protein family of transcription factors that possess a unique tyrosine (Y)
      residue instead of an arginine (R) residue in the bHLH region. We have determined
      that Srb1 message levels increase in a time dependent manner during growth under
      oxygen deprivation (hypoxia). To further understand the role of Srb1 during
      infection and hypoxia, we silenced the gene encoding Srb1 using RNA interference
      (RNAi); characterized the resulting phenotype, determined its response to
      hypoxia, and its ability to cause disease within an infected host. Silencing of
      Srb1 resulted in a strain of H. capsulatum that is incapable of surviving in
      vitro hypoxia. We found that without complete Srb1 expression, H. capsulatum is
      killed by murine macrophages and avirulent in mice given a lethal dose of yeasts.
      Additionally, silencing Srb1 inhibited the hypoxic upregulation of other known H.
      capsulatum hypoxia-responsive genes (HRG), and genes that encode ergosterol
      biosynthetic enzymes. Consistent with these regulatory functions, Srb1 silenced
      H. capsulatum cells were hypersensitive to the antifungal azole drug
      itraconazole. These data support the theory that the H. capsulatum SREBP is
      critical for hypoxic adaptation and is required for H. capsulatum virulence.

PMID- 27711234
TI  - A Virtual Reality Full Body Illusion Improves Body Image Disturbance in Anorexia
      Nervosa.
AB  - BACKGROUND: Patients with anorexia nervosa (AN) have a persistent distorted
      experience of the size of their body. Previously we found that the Rubber Hand
      Illusion improves hand size estimation in this group. Here we investigated
      whether a Full Body Illusion (FBI) affects body size estimation of body parts
      more emotionally salient than the hand. In the FBI, analogue to the RHI,
      participants experience ownership over an entire virtual body in VR after
      synchronous visuo-tactile stimulation of the actual and virtual body. METHODS AND
      RESULTS: We asked participants to estimate their body size (shoulders, abdomen,
      hips) before the FBI was induced, directly after induction and at ~2 hour 45
      minutes follow-up. The results showed that AN patients (N = 30) decrease the
      overestimation of their shoulders, abdomen and hips directly after the FBI was
      induced. This effect was strongest for estimates of circumference, and also
      observed in the asynchronous control condition of the illusion. Moreover, at
      follow-up, the improvements in body size estimation could still be observed in
      the AN group. Notably, the HC group (N = 29) also showed changes in body size
      estimation after the FBI, but the effect showed a different pattern than that of
      the AN group. CONCLUSION: The results lead us to conclude that the disturbed
      experience of body size in AN is flexible and can be changed, even for highly
      emotional body parts. As such this study offers novel starting points from which
      new interventions for body image disturbance in AN can be developed.

PMID- 27711235
TI  - Transcriptome Profile of the Chicken Thrombocyte: New Implications as an Advanced
      Immune Effector Cell.
AB  - Thrombocytes are nucleated platelets involved in immune functions such as
      pathogen recognition and release of pro-inflammatory bioactive compounds when
      exposed to bacterial and viral molecules. However, the complete role of these
      cells in innate and adaptive immune responses is not understood, and little is
      known about their biology at the molecular-genetic level. Highly sensitive RNA
      sequencing technologies were used to analyze the complete transcriptome of
      thrombocytes for the first time with analytical resolution focused on cell-based
      components of the immune system/response. Amongst all the genes listed in the
      current chicken genome assembly, 10,041 gene transcripts were found in the
      chicken thrombocyte. After 1-hour in vitro stimulation with lipopolysaccharide
      (LPS, Salmonella minnesota), 490 genes were upregulated and 359 genes were
      downregulated, respectively, with at least a 1-fold change relative to unexposed
      thrombocytes. Additionally, by constructing a de novo assembly, we were able to
      identify a total of 3,030 novel genes in the thrombocyte transcriptome. The
      information generated here is useful in development of novel solutions to lower
      the economic burden and zoonotic threat that accompanies infectious diseases for
      birds and fish. In addition, the resources created here have translational
      utility as a model system to find orthologous genes and genes related to its
      enucleated counterpart, the platelet.

PMID- 27711236
TI  - An Examination of Not-For-Profit Stakeholder Networks for Relationship
      Management: A Small-Scale Analysis on Social Media.
AB  - Using a small-scale descriptive network analysis approach, this study highlights
      the importance of stakeholder networks for identifying valuable stakeholders and
      the management of existing stakeholders in the context of mental health not-for
      profit services. We extract network data from the social media brand pages of
      three health service organizations from the U.S., U.K., and Australia, to
      visually map networks of 579 social media brand pages (represented by nodes),
      connected by 5,600 edges. This network data is analyzed using a collection of
      popular graph analysis techniques to assess the differences in the way each of
      the service organizations manage stakeholder networks. We also compare node meta
      information against basic topology measures to emphasize the importance of
      effectively managing relationships with stakeholders who have large external
      audiences. Implications and future research directions are also discussed.

PMID- 27711237
TI  - Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the
      Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation.
AB  - Radiotherapy with heavy ions is considered advantageous compared to irradiation
      with photons due to the characteristics of the Braggs peak and the high linear
      energy transfer (LET) value. To understand the mechanisms of cellular responses
      to different LET values and dosages of heavy ion radiation, we analyzed the
      proteomic profiles of mouse embryo fibroblast MEF cells exposed to two doses from
      different LET values of heavy ion 12C. Total proteins were extracted from these
      cells and examined by Q Exactive with Liquid Chromatography (LC)-Electrospray
      Ionization (ESI) Tandem MS (MS/MS). Using bioinformatics approaches,
      differentially expressed proteins with 1.5 or 2.0-fold changes between different
      dosages of exposure were compared. With the higher the dosage and/or LET of ion
      irradiation, the worse response the cells were in terms of protein expression.
      For instance, compared to the control (0 Gy), 771 (20.2%) proteins in cells
      irradiated at 0.2 Gy of carbon-ion radiation with 12.6 keV/MUm, 313 proteins
      (8.2%) in cells irradiated at 2 Gy of carbon-ion radiation with 12.6 keV/MUm, and
      243 proteins (6.4%) in cells irradiated at 2 Gy of carbon-ion radiation with 31.5
      keV/MUm exhibited changes of 1.5-fold or greater. Gene ontology (GO) analysis,
      Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Munich Information
      Center for Protein Sequences (MIPS) analysis, and BioCarta analysis all indicated
      that RNA metabolic processes (RNA splicing, destabilization and deadenylation)
      and proteasome pathways may play key roles in the cellular response to heavy-ion
      irradiation. Proteasome pathways ranked highest among all biological processes
      associated with heavy carbon-ion irradiation. In addition, network analysis
      revealed that cellular pathways involving proteins such as Col1a1 and Fn1
      continued to respond to high dosages of heavy-ion irradiation, suggesting that
      these pathways still protect cells against damage. However, pathways such as
      those involving Ikbkg1 responded better at lower dosages than at higher dosages,
      implying that cell damage would occur when the networks involving these proteins
      stop responding. Our investigation provides valuable proteomic information for
      elucidating the mechanism of biological effects induced by carbon ions in
      general.

PMID- 27711238
TI  - The Highly Selective and Near-Quantitative Conversion of Glucose to 5
      Hydroxymethylfurfural Using Ionic Liquids.
AB  - A number of ionic liquids have been shown to be excellent solvents for
      lignocellulosic biomass processing, and some of these are particularly effective
      in the production of the versatile chemical building block 5
      hydroxymethylfurfural (HMF). In this study, the production of HMF from the simple
      sugar glucose in ionic liquid media is discussed. Several aspects of the
      selective catalytic formation of HMF from glucose have been elucidated using
      metal halide salts in two distinct ionic liquids, 1-butyl-3-methylimidazolium
      chloride and 1-butyl-3-methylimidazolium hydrogen sulfate as well as mixtures of
      these, revealing key features for accelerating the desired reaction and
      suppressing byproduct formation. The choice of ionic liquid anion is revealed to
      be of particular importance, with low HMF yields in the case of hydrogen sulfate
      based salts, which are reported to be effective for HMF production from fructose.
      The most successful system investigated in this study led to almost quantitative
      conversion of glucose to HMF (90% in only 30 minutes using 7 mol% catalyst
      loading at 120 degrees C) in a system which is selective for the desired product,
      has low energy intensity and is environmentally benign.

PMID- 27711239
TI  - Hemizygous Deletion on Chromosome 3p26.1 Is Associated with Heavy Smoking among
      African American Subjects in the COPDGene Study.
AB  - Many well-powered genome-wide association studies have identified genetic
      determinants of self-reported smoking behaviors and measures of nicotine
      dependence, but most have not considered the role of structural variants, such as
      copy number variation (CNVs), influencing these phenotypes. Here, we included
      2,889 African American and 6,187 non-Hispanic White subjects from the COPDGene
      cohort (http://www.copdgene.org) to carefully investigate the role of polymorphic
      CNVs across the genome on various measures of smoking behavior. We identified a
      CNV component (a hemizygous deletion) on chromosome 3p26.1 associated with two
      quantitative phenotypes related to smoking behavior among African Americans. This
      polymorphic hemizygous deletion is significantly associated with pack-years and
      cigarettes smoked per day among African American subjects in the COPDGene study.
      We sought evidence of replication in African Americans from the population based
      Atherosclerosis Risk in Communities (ARIC) study. While we observed similar CNV
      counts, the extent of exposure to cigarette smoking among ARIC subjects was quite
      different and the smaller sample size of heavy smokers in ARIC severely limited
      statistical power, so we were unable to replicate our findings from the COPDGene
      cohort. But meta-analyses of COPDGene and ARIC study subjects strengthened our
      association signal. However, a few linkage studies have reported suggestive
      linkage to the 3p26.1 region, and a few genome-wide association studies (GWAS)
      have reported markers in the gene (GRM7) nearest to this 3p26.1 area of
      polymorphic deletions are associated with measures of nicotine dependence among
      subjects of European ancestry.

PMID- 27711240
TI  - Reference Ranges and Association of Age and Lifestyle Characteristics with
      Testosterone, Sex Hormone Binding Globulin, and Luteinizing Hormone among 1166
      Western Chinese Men.
AB  - Decreased total testosterone (TT) is the recommended metric to identify age
      related hypogonadism. However, average TT and the extent to which it varies by
      age, can vary substantially among different populations. Population-specific
      reference ranges are needed to understand normal versus abnormal TT levels.
      Therefore, the goal for this study was to describe androgen concentrations and
      their correlates among Western Chinese men. We completed a population-based,
      cross-sectional study including 227 young adults (YA) (20-39 years) and 939 older
      adults (OA) (40-89 years). We measured TT, sex-hormone binding globulin (SHBG),
      luteinizing hormone (LH), testosterone secreting index (TSI), and calculated free
      testosterone (cFT). Reference ranges for this population were determined using
      average YA concentrations. Multivariable regression models were used to predict
      hormone concentrations adjusting for age, waist-to-height ratio (WHR), marital
      status, education, occupation, smoking, alcohol, blood glucose, and blood
      pressure. Among OA, 3.8% had low TT, 15.2% had low cFT, 26.3% had low TSI, 21.6%
      had high SHBG, and 6.1% had high LH. Average cFT was significantly lower in OA
      (0.30 nmol/L; standard deviation (SD): 0.09) versus YA (0.37; SD: 0.11) but TT
      was not different in OA (16.82 nmol/L; SD: 4.80) versus YA (16.88; SD: 5.29). In
      adjusted models increasing age was significantly associated with increased SHBG
      or LH, and decreased cFT or TSI; however, TT was not significantly associated
      with age (beta = 0.02 nmol/L; 95% confidence interval (CI): -0.01, 0.04). Higher
      WHR was associated with significantly decreased TT, SHBG, TSI, and LH. The only
      variable significantly related to cFT was age (beta = -0.0033; 95% CI:-0.0037, 
      0.0028); suggesting that cFT measurements would not be confounded by other
      lifestyle factors. In conclusion, cFT, but not TT, varies with age in this
      population, suggesting cFT may be a better potential marker for age-related
      androgen deficiency than TT among Western Chinese men.

PMID- 27711241
TI  - Population Genetic Structure of Glycyrrhiza inflata B. (Fabaceae) Is Shaped by
      Habitat Fragmentation, Water Resources and Biological Characteristics.
AB  - BACKGROUND: Habitat fragmentation, water resources and biological characteristics
      are important factors that shape the genetic structure and geographical
      distribution of desert plants. Analysis of the relationships between these
      factors and population genetic variation should help to determine the
      evolutionary potential and conservation strategies for genetic resources for
      desert plant populations. As a traditional Chinese herb, Glycyrrhiza inflata B.
      (Fabaceae) is restricted to the fragmented desert habitat in China and has
      undergone a dramatic decline due to long-term over-excavation. Determining the
      genetic structure of the G. inflata population and identifying a core collection
      could help with the development of strategies to conserve this species. RESULTS:
      We investigated the genetic variation of 25 G. inflata populations based on
      microsatellite markers. A high level of population genetic divergence (FST =
      0.257), population bottlenecks, reduced gene flow and moderate genetic variation
      (HE = 0.383) were detected. The genetic distances between the populations
      significantly correlated with the geographical distances, and this suggests that
      habitat fragmentation has driven a special genetic structure of G. inflata in
      China through isolation by distance. STRUCTURE analysis showed that G. inflata
      populations were structured into three clusters and that the populations belonged
      to multiple water systems, which suggests that water resources were related to
      the genetic structure of G. inflata. In addition, the biological characteristics
      of the perennial species G. inflata, such as its long-lived seeds, asexual
      reproduction, and oasis ecology, may be related to its resistance to habitat
      fragmentation. A core collection of G. inflata, that included 57 accessions was
      further identified, which captured the main allelic diversity of G. inflata.
      CONCLUSIONS: Recent habitat fragmentation has accelerated genetic divergence. The
      population genetic structure of G. inflata has been shaped by habitat
      fragmentation, water resources and biological characteristics. This genetic
      information and core collection will facilitate the conservation of wild
      germplasm and breeding of this Chinese medicinal plant.

PMID- 27711242
TI  - Developing the Stroke Exercise Preference Inventory (SEPI).
AB  - BACKGROUND: Physical inactivity is highly prevalent after stroke, increasing the
      risk of poor health outcomes including recurrent stroke. Tailoring of exercise
      programs to individual preferences can improve adherence, but no tools exist for
      this purpose in stroke. METHODS: We identified potential questionnaire items for
      establishing exercise preferences via: (i) our preliminary Exercise Preference
      Questionnaire in stroke, (ii) similar tools used in other conditions, and (iii)
      expert panel consultations. The resulting 35-item questionnaire (SEPI-35) was
      administered to stroke survivors, along with measures of disability, depression,
      anxiety, fatigue and self-reported physical activity. Exploratory factor analysis
      was used to identify a factor structure in exercise preferences, providing a
      framework for item reduction. Associations between exercise preferences and
      personal characteristics were analysed using multivariable regression. RESULTS: A
      group of 134 community-dwelling stroke survivors (mean age 64.0, SD 13.3)
      participated. Analysis of the SEPI-35 identified 7 exercise preference factors
      (Supervision-support, Confidence-challenge, Health-wellbeing, Exercise context,
      Home-alone, Similar others, Music-TV). Item reduction processes yielded a 13-item
      version (SEPI-13); in analysis of this version, the original factor structure was
      maintained. Lower scores on Confidence-challenge were significantly associated
      with disability (p = 0.002), depression (p = 0.001) and fatigue (p = 0.001). Self
      reported barriers to exercise were particularly prevalent in those experiencing
      fatigue and anxiety. CONCLUSIONS: The SEPI-13 is a brief instrument that allows
      assessment of exercise preferences and barriers in the stroke population. This
      new tool can be employed by health professionals to inform the development of
      individually tailored exercise interventions.

PMID- 27711244
TI  - Is the Taklimakan Desert Highway Shelterbelt Sustainable to Long-Term Drip
      Irrigation with High Saline Groundwater?
AB  - Freshwater resources are scarce in desert regions. Highly saline groundwater of
      different salinity is being used to drip irrigate the Taklimakan Desert Highway
      Shelterbelt with a double-branch-pipe system controlling the irrigation cycles.
      In this study, to evaluate the dynamics of soil moisture and salinity under the
      current irrigation system, soil samples were collected to a 2-m depth in the
      shelterbelt planted for different years and irrigated with different groundwater
      salinities, and soil moisture and salinity were analyzed. The results showed that
      both depletion of soil moisture and increase of topsoil salinity occurred
      simultaneously during one irrigation cycle. Soil moisture decreased from 27.4% to
      2.4% for a 15-day irrigation cycle and from 26.4% to 2.7% for a 10-day-cycle,
      respectively. Topsoil electrical conductivity (EC) increased from 0.64 to 3.32
      dS/m and 0.70 to 3.99 dS/m for these two irrigation cycles. With increased
      shelterbelt age, profiled average soil moisture (0-200 cm) reduced from 12.8% (1
      year) to 7.1% (10-year); however, soil moisture in 0-20-cm increased, while
      topsoil salinity decreased. In addition, irrigation salinity mainly affected soil
      salinity in the 0-20-cm range. We conclude that water supply with the double
      branch-pipe is a feasible irrigation method for the Taklimakan Desert Highway
      Shelterbelt, and our findings provide a model for shelterbelt construction and
      sustainable management when using highly saline water for irrigation in analogous
      habitats.

PMID- 27711243
TI  - cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of
      Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila
      melanogaster Larvae.
AB  - While the mammalian brain functions within a very narrow range of oxygen
      concentrations and temperatures, the fruit fly, Drosophila melanogaster, has
      employed strategies to deal with a much wider range of acute environmental
      stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase
      (PKG), has been shown to regulate thermotolerance in many stress-adapted species,
      including Drosophila, and could be a potential therapeutic target in the
      treatment of hyperthermia in mammals. Whereas previous thermotolerance studies
      have looked at the effects of PKG variation on Drosophila behavior or excitatory
      postsynaptic potentials at the neuromuscular junction (NMJ), little is known
      about PKG effects on presynaptic mechanisms. In this study, we characterize
      presynaptic calcium ([Ca2+]i) dynamics at the Drosophila larval NMJ to determine
      the effects of high temperature stress on synaptic transmission. We investigated
      the neuroprotective role of PKG modulation both genetically using RNA
      interference (RNAi), and pharmacologically, to determine if and how PKG affects
      presynaptic [Ca2+]i dynamics during hyperthermia. We found that PKG activity
      modulates presynaptic neuronal Ca2+ responses during acute hyperthermia, where
      PKG activation makes neurons more sensitive to temperature-induced failure of
      Ca2+ flux and PKG inhibition confers thermotolerance and maintains normal Ca2+
      dynamics under the same conditions. Targeted motoneuronal knockdown of PKG using
      RNAi demonstrated that decreased PKG expression was sufficient to confer
      thermoprotection. These results demonstrate that the PKG pathway regulates
      presynaptic motoneuronal Ca2+ signaling to influence thermotolerance of
      presynaptic function during acute hyperthermia.

PMID- 27711246
TI  - Fault Diagnosis for Rotating Machinery: A Method based on Image Processing.
AB  - Rotating machinery is one of the most typical types of mechanical equipment and
      plays a significant role in industrial applications. Condition monitoring and
      fault diagnosis of rotating machinery has gained wide attention for its
      significance in preventing catastrophic accident and guaranteeing sufficient
      maintenance. With the development of science and technology, fault diagnosis
      methods based on multi-disciplines are becoming the focus in the field of fault
      diagnosis of rotating machinery. This paper presents a multi-discipline method
      based on image-processing for fault diagnosis of rotating machinery. Different
      from traditional analysis method in one-dimensional space, this study employs
      computing method in the field of image processing to realize automatic feature
      extraction and fault diagnosis in a two-dimensional space. The proposed method
      mainly includes the following steps. First, the vibration signal is transformed
      into a bi-spectrum contour map utilizing bi-spectrum technology, which provides a
      basis for the following image-based feature extraction. Then, an emerging
      approach in the field of image processing for feature extraction, speeded-up
      robust features, is employed to automatically exact fault features from the
      transformed bi-spectrum contour map and finally form a high-dimensional feature
      vector. To reduce the dimensionality of the feature vector, thus highlighting
      main fault features and reducing subsequent computing resources, t-Distributed
      Stochastic Neighbor Embedding is adopt to reduce the dimensionality of the
      feature vector. At last, probabilistic neural network is introduced for fault
      identification. Two typical rotating machinery, axial piston hydraulic pump and
      self-priming centrifugal pumps, are selected to demonstrate the effectiveness of
      the proposed method. Results show that the proposed method based on image
      processing achieves a high accuracy, thus providing a highly effective means to
      fault diagnosis for rotating machinery.

PMID- 27711245
TI  - The Association between Educational Level and Cardiovascular and Cerebrovascular
      Diseases within the EPICOR Study: New Evidence for an Old Inequality Problem.
AB  - BACKGROUND: A consistent association has been reported between low socioeconomic
      status (SES) and cardiovascular events (CE), whereas the association between SES
      and cerebrovascular events (CBVD) is less clear. The aim of this study was to
      investigate the association between SES (measured using education) and CE/CBVD in
      a cohort study, as well as to investigate lifestyle and clinical risk factors, to
      help to clarify the mechanisms by which SES influences CE/CBVD. MATERIAL AND
      METHODS: We searched for diagnoses of CE and CBVD in the clinical records of
      47,749 members of the EPICOR cohort (average follow-up time: 11 years). SES was
      determined by the relative index of inequality (RII). RESULTS: A total of 1,156
      CE and 468 CBVD were found in the clinical records. An increased risk of CE was
      observed in the crude Cox model for the third tertile of RII compared to the
      first tertile (hazard ratio [HR] = 1.39; 95% confidence interval [CI] 1.21-1.61).
      The increased risk persisted after adjustment for lifestyle risk factors (HR =
      1.19; 95%CI 1.02-1.38), clinical risk factors (HR = 1.35; 95%CI 1.17-1.56), and
      after full adjustment (HR = 1.17; 95%CI 1.01-1.37). Structural equation model
      showed that lifestyle rather than clinical risk factors are involved in the
      mechanisms by which education influences CE. No significant association was found
      between education and CBVD. A strong relationship was observed between education
      and diabetes at baseline. CONCLUSION: The most important burden of inequality in
      CE incidence in Italy is due to lifestyle risk factors.

PMID- 27711247
TI  - Predicting the Response to Intravenous Immunoglobulins in an Animal Model of
      Chronic Neuritis.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disabling
      autoimmune disorder of the peripheral nervous system (PNS). Intravenous
      immunoglobulins (IVIg) are effective in CIDP, but the treatment response varies
      greatly between individual patients. Understanding this interindividual
      variability and predicting the response to IVIg constitute major clinical
      challenges in CIDP. We previously established intercellular adhesion molecule
      (ICAM)-1 deficient non-obese diabetic (NOD) mice as a novel animal model of CIDP.
      Here, we demonstrate that similar to human CIDP patients, ICAM-1 deficient NOD
      mice respond to IVIg treatment by clinical and histological measures. Nerve
      magnetic resonance imaging and histology demonstrated that IVIg ameliorates
      abnormalities preferentially in distal parts of the sciatic nerve branches. The
      IVIg treatment response also featured great heterogeneity allowing us to identify
      IVIg responders and non-responders. An increased production of interleukin (IL)
      17 positively predicted IVIg treatment responses. In human sural nerve biopsy
      sections, high numbers of IL-17 producing cells were associated with younger age
      and shorter disease duration. Thus, our novel animal model can be utilized to
      identify prognostic markers of treatment responses in chronic inflammatory
      neuropathies and we identify IL-17 production as one potential such prognostic
      marker.

PMID- 27711248
TI  - Tetrahydrobiopterin Supplementation: Elevation of Tissue Biopterin Levels
      Accompanied by a Relative Increase in Dihydrobiopterin in the Blood and the Role
      of Probenecid-Sensitive Uptake in Scavenging Dihydrobiopterin in the Liver and
      Kidney of Rats.
AB  - Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS)
      and aromatic amino acid hydroxylases. BH4 and 7,8-dihydrobiopterin (BH2) are
      metabolically interchangeable at the expense of NADPH. Exogenously administered
      BH4 can be metabolized by the body, similar to vitamins. At present, synthetic
      BH4 is used as an orphan drug for patients with inherited diseases requiring BH4
      supplementation. BH4 supplementation has also drawn attention as a means of
      treating certain cardiovascular symptoms, however, its application in human
      patients remains limited. Here, we tracked biopterin (BP) distribution in blood,
      bile, urine, liver, kidney and brain after BH4 administration (5 mg/kg rat, i.v.)
      with or without prior treatment with probenecid, a potent inhibitor of uptake
      transporters particularly including organic anion transporter families such as
      OTA1 and OAT3. The rapid excretion of BP in urine was driven by elevated blood
      concentrations and its elimination reached about 90% within 120 min. In the very
      early period, BP was taken up by the liver and kidney and gradually released back
      to the blood. BH4 administration caused a considerable decrease in the BH4% in
      blood BP as an inevitable compensatory process. Probenecid treatment slowed down
      the decrease in blood BP and simultaneously inhibited its initial rapid excretion
      in the kidney. At the same time, the BH4% was further lowered, suggesting that
      the probenecid-sensitive BP uptake played a crucial role in BH2 scavenging in
      vivo. This suggested that the overproduced BH2 was taken up by organs by means of
      the probenecid-sensitive process, and was then scavenged by counter-conversion to
      BH4 via the BH4 salvage pathway. Taken together, BH4 administration was effective
      at raising BP levels in organs over the course of hours but with extremely low
      efficiency. Since a high BH2 relative to BH4 causes NOS dysfunction, the lowering
      of the BH4% must be avoided in practice, otherwise the desired effect of the
      supplementation in ameliorating NOS dysfunction would be spoiled.

PMID- 27711249
TI  - "On My Own, but Not Alone" - Adolescents' Experiences of Internet-Delivered
      Cognitive Behavior Therapy for Obsessive-Compulsive Disorder.
AB  - INTRODUCTION: Childhood Obsessive-Compulsive Disorder (OCD) is a prevalent and
      impairing condition that can be effectively treated with Cognitive Behavior
      Therapy (CBT). However, a majority of children and adolescents do not have access
      to CBT. Internet-delivered CBT (ICBT) has been suggested as a way to increase
      availability to effective psychological treatments. Yet, the research on ICBT in
      children and adolescents has been lagging behind significantly both when it comes
      to quantitative as well as qualitative studies. The aim of the current study was
      to describe the experience of ICBT in adolescents with OCD. METHOD: Eight
      adolescents with OCD that had received ICBT were interviewed with qualitative
      methodology regarding their experiences of the intervention. Data was summarized
      into thematic categories. RESULTS: Two overarching themes were identified,
      autonomy and support, each consisting of three primary themes (self-efficacy,
      flexibility, secure self-disclosure and clinician support, parental support,
      identification/normalization, respectively). CONCLUSIONS: The experiential
      hierarchical model that was identified in this study is, in part, transferrable
      to previous research. In addition, it highlights the need of further study of
      important process variables of ICBT in young patient populations.

PMID- 27711250
TI  - Five-Year Antimicrobial Resistance Patterns of Urinary Escherichia coli at an
      Australian Tertiary Hospital: Time Series Analyses of Prevalence Data.
AB  - This study describes the antimicrobial resistance temporal trends and seasonal
      variation of Escherichia coli (E. coli) urinary tract infections (UTIs) over five
      years, from 2009 to 2013, and compares prevalence of resistance in hospital- and
      community-acquired E. coli UTI. A cross sectional study of E. coli UTIs from
      patients attending a tertiary referral hospital in Canberra, Australia was
      undertaken. Time series analysis was performed to illustrate resistance trends.
      Only the first positive E. coli UTI per patient per year was included in the
      analysis. A total of 15,022 positive cultures from 8724 patients were identified.
      Results are based on 5333 first E. coli UTIs, from 4732 patients, of which 84.2%
      were community-acquired. Five-year hospital and community resistance rates were
      highest for ampicillin (41.9%) and trimethoprim (20.7%). Resistance was lowest
      for meropenem (0.0%), nitrofurantoin (2.7%), piperacillin-tazobactam (2.9%) and
      ciprofloxacin (6.5%). Resistance to amoxycillin-clavulanate, cefazolin,
      gentamicin and piperacillin-tazobactam were significantly higher in hospital-
      compared to community-acquired UTIs (9.3% versus 6.2%; 15.4% versus 9.7%; 5.2%
      versus 3.7% and 5.2% versus 2.5%, respectively). Trend analysis showed
      significant increases in resistance over five years for amoxycillin-clavulanate,
      trimethoprim, ciprofloxacin, nitrofurantoin, trimethoprim-sulphamethoxazole,
      cefazolin, ceftriaxone and gentamicin (P<0.05, for all) with seasonal pattern
      observed for trimethoprim resistance (augmented Dickey-Fuller statistic = 4.136;
      P = 0.006). An association between ciprofloxacin resistance, cefazolin resistance
      and ceftriaxone resistance with older age was noted. Given the relatively high
      resistance rates for ampicillin and trimethoprim, these antimicrobials should be
      reconsidered for empirical treatment of UTIs in this patient population. Our
      findings have important implications for UTI treatment based on setting of
      acquisition.

PMID- 27711251
TI  - A Comparison of the Costs and Benefits of Bacterial Gene Expression.
AB  - To study how a bacterium allocates its resources, we compared the costs and
      benefits of most (86%) of the proteins in Escherichia coli K-12 during growth in
      minimal glucose medium. The cost or investment in each protein was estimated from
      ribosomal profiling data, and the benefit of each protein was measured by
      assaying a library of transposon mutants. We found that proteins that are
      important for fitness are usually highly expressed, and 95% of these proteins are
      expressed at above 13 parts per million (ppm). Conversely, proteins that do not
      measurably benefit the host (with a benefit of less than 5% per generation) tend
      to be weakly expressed, with a median expression of 13 ppm. In aggregate, genes
      with no detectable benefit account for 31% of protein production, or about 22% if
      we correct for genetic redundancy. Although some of the apparently unnecessary
      expression could have subtle benefits in minimal glucose medium, the majority of
      the burden is due to genes that are important in other conditions. We propose
      that at least 13% of the cell's protein is "on standby" in case conditions
      change.

PMID- 27711253
TI  - HSPB1 Enhances SIRT2-Mediated G6PD Activation and Promotes Glioma Cell
      Proliferation.
AB  - Heat shock proteins belong to a conserved protein family and are involved in
      multiple cellular processes. Heat shock protein 27 (Hsp27), also known as heat
      HSPB1, participates in cellular responses to not only heat shock, but also
      oxidative or chemical stresses. However, the contribution of HSPB1 to anti
      oxidative response remains unclear. Here, we show that HSPB1 activates G6PD in
      response to oxidative stress or DNA damage. HSPB1 enhances the binding between
      G6PD and SIRT2, leading to deacetylation and activation of G6PD. Besides, HSPB1
      activates G6PD to sustain cellular NADPH and pentose production in glioma cells.
      High expression of HSPB1 correlates with poor survivalrate of glioma patients.
      Together, our study uncovers the molecular mechanism by which HSPB1 activates
      G6PD to protect cells from oxidative and DNA damage stress.

PMID- 27711252
TI  - PG1058 Is a Novel Multidomain Protein Component of the Bacterial Type IX
      Secretion System.
AB  - Porphyromonas gingivalis utilises the Bacteroidetes-specific type IX secretion
      system (T9SS) to export proteins across the outer membrane (OM), including
      virulence factors such as the gingipains. The secreted proteins have a conserved
      carboxy-terminal domain essential for type IX secretion that is cleaved upon
      export. In P. gingivalis the T9SS substrates undergo glycosylation with anionic
      lipopolysaccharide (A-LPS) and are attached to the OM. In this study, comparative
      analyses of 24 Bacteroidetes genomes identified ten putative novel components of
      the T9SS in P. gingivalis, one of which was PG1058. Computer modelling of the
      PG1058 structure predicted a novel N- to C-terminal architecture comprising a
      tetratricopeptide repeat (TPR) domain, a beta-propeller domain, a
      carboxypeptidase regulatory domain-like fold (CRD) and an OmpA_C-like putative
      peptidoglycan binding domain. Inactivation of pg1058 in P. gingivalis resulted in
      loss of both colonial pigmentation and surface-associated proteolytic activity; a
      phenotype common to T9SS mutants. Immunoblot and LC-MS/MS analyses of subcellular
      fractions revealed T9SS substrates accumulated within the pg1058 mutant periplasm
      whilst whole-cell ELISA showed the Kgp gingipain was absent from the cell
      surface, confirming perturbed T9SS function. Immunoblot, TEM and whole-cell ELISA
      analyses indicated A-LPS was produced and present on the pg1058 mutant cell
      surface although it was not linked to T9SS substrate proteins. This indicated
      that PG1058 is crucial for export of T9SS substrates but not for the
      translocation of A-LPS. PG1058 is a predicted lipoprotein and was localised to
      the periplasmic side of the OM using whole-cell ELISA, immunoblot and LC-MS/MS
      analyses of subcellular fractions. The structural prediction and localisation of
      PG1058 suggests that it may have a role as an essential scaffold linking the
      periplasmic and OM components of the T9SS.

PMID- 27711254
TI  - Reversible Cryopreservation of Living Cells Using an Electron Microscopy Cryo
      Fixation Method.
AB  - Rapid cooling of aqueous solutions is a useful approach for two important
      biological applications: (I) cryopreservation of cells and tissues for long-term
      storage, and (II) cryofixation for ultrastructural investigations by electron and
      cryo-electron microscopy. Usually, both approaches are very different in
      methodology. Here we show that a novel, fast and easy to use cryofixation
      technique called self-pressurized rapid freezing (SPRF) is-after some adaptations
      also a useful and versatile technique for cryopreservation. Sealed metal tubes
      with high thermal diffusivity containing the samples are plunged into liquid
      cryogen. Internal pressure builds up reducing ice crystal formation and therefore
      supporting reversible cryopreservation through vitrification of cells. After
      rapid rewarming of pressurized samples, viability rates of > 90% can be reached,
      comparable to best-performing of the established rapid cooling devices tested. In
      addition, the small SPRF tubes allow for space-saving sample storage and the
      sealed containers prevent contamination from or into the cryogen during freezing,
      storage, or thawing.

PMID- 27711255
TI  - Scaffold Role of DUSP22 in ASK1-MKK7-JNK Signaling Pathway.
AB  - Mitogen-activated protein kinases (MAPKs) are involved in a variety of
      intracellular events such as gene expression, cell proliferation, and programmed
      cell death. MAPKs are activated by dual phosphorylation on threonine and tyrosine
      residues through sequential activation of protein kinases. Recent studies have
      shown that the protein kinases involved in MAPK signal transductions might be
      organized into signaling complexes by scaffold proteins. These scaffold proteins
      are essential regulators that function by assembling the relevant molecular
      components in mammalian cells. In this study, we report that dual-specificity
      phosphatase 22 (DUSP22), a member of the protein tyrosine phosphatase family,
      acts as a distinct scaffold protein in c-Jun N-terminal kinase (JNK) signaling.
      DUSP22 increased the phosphorylation in the activation loop of JNK regardless of
      its phosphatase activity but had no effect on phosphorylation levels of ERK and
      p38 in mammalian cells. Furthermore, DUSP22 selectively associated with apoptosis
      signal-regulating kinase 1 (ASK1), MAPK kinase 7 (MKK7), and JNK1/2. Both JNK
      phosphorylation and JNK-mediated apoptosis increased in a concentration-dependent
      manner regardless of DUSP22 phosphatase activity at low DUSP22 concentrations,
      but then decreased at higher DUSP22 concentrations, which is the prominent
      feature of a scaffold protein. Thus, our data suggest that DUSP22 regulates cell
      death by acting as a scaffold protein for the ASK1-MKK7-JNK signal transduction
      pathway independently of its phosphatase activity.

PMID- 27711256
TI  - The Effect of Gender on Mesenchymal Stem Cell (MSC) Efficacy in Neonatal
      Hyperoxia-Induced Lung Injury.
AB  - BACKGROUND: Mesenchymal stem cells (MSC) improve alveolar and vascular structures
      in experimental models of bronchopulmonary dysplasia (BPD). Female MSC secrete
      more anti-inflammatory and pro-angiogenic factors as compared to male MSC.
      Whether the therapeutic efficacy of MSC in attenuating lung injury in an
      experimental model of BPD is influenced by the sex of the donor MSC or recipient
      is unknown. Here we tested the hypothesis that female MSC would have greater lung
      regenerative properties than male MSC in experimental BPD and this benefit would
      be more evident in males. OBJECTIVE: To determine whether intra-tracheal (IT)
      administration of female MSC to neonatal rats with experimental BPD has more
      beneficial reparative effects as compared to IT male MSC. METHODS: Newborn
      Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2) from postnatal
      day (P) 2- P21 were randomly assigned to receive male or female IT bone marrow
      (BM)-derived green fluorescent protein (GFP+) MSC (1 x 106 cells/50 MUl), or
      Placebo on P7. Pulmonary hypertension (PH), vascular remodeling, alveolarization,
      and angiogenesis were assessed at P21. PH was determined by measuring right
      ventricular systolic pressure (RVSP) and pulmonary vascular remodeling was
      evaluated by quantifying the percentage of muscularized peripheral pulmonary
      vessels. Alveolarization was evaluated by measuring mean linear intercept (MLI)
      and radial alveolar count (RAC). Angiogenesis was determined by measuring
      vascular density. Data are expressed as mean +/- SD, and analyzed by ANOVA.
      RESULTS: There were no significant differences in the RA groups. Exposure to
      hyperoxia resulted in a decrease in vascular density and RAC, with a significant
      increase in MLI, RVSP, and the percentage of partially and fully muscularized
      pulmonary arterioles. Administration of both male and female MSC significantly
      improved vascular density, alveolarization, RVSP, percent of muscularized vessels
      and alveolarization. Interestingly, the improvement in PH and vascular remodeling
      was more robust in the hyperoxic rodents who received MSC from female donors. In
      keeping with our hypothesis, male animals receiving female MSC, had a greater
      improvement in vascular remodeling. This was accompanied by a more significant
      decrease in lung pro-inflammatory markers and a larger increase in anti
      inflammatory and pro-angiogenic markers in male rodents that received female MSC.
      There were no significant differences in MSC engraftment among groups.
      CONCLUSIONS: Female BM-derived MSC have greater therapeutic efficacy than male
      MSC in reducing neonatal hyperoxia-induced lung inflammation and vascular
      remodeling. Furthermore, the beneficial effects of female MSC were more
      pronounced in male animals. Together, these findings suggest that female MSC
      maybe the most potent BM-derived MSC population for lung repair in severe BPD
      complicated by PH.

PMID- 27711257
TI  - Ultra-Specific Isolation of Circulating Tumor Cells Enables Rare-Cell RNA
      Profiling.
AB  - The clinical potential of circulating tumor cells (CTCs) in managing cancer
      metastasis is significant. However, low CTC isolation purities from patient blood
      have hindered sensitive molecular assays of these rare cells. Described herein is
      the ultra-pure isolation of CTCs from patient blood samples and how this platform
      has enabled highly specific molecular (mRNA and miRNA) profiling of patient CTCs.

PMID- 27711258
TI  - Controllable Sliding Transfer of Wafer-Size Graphene.
AB  - The innovative design of sliding transfer based on a liquid substrate can
      succinctly transfer high-quality, wafer-size, and contamination-free graphene
      within a few seconds. Moreover, it can be extended to transfer other 2D
      materials. The efficient sliding transfer approach can obtain high-quality and
      large-area graphene for fundamental research and industrial applications.

PMID- 27711259
TI  - Recent Progress in Self-Supported Metal Oxide Nanoarray Electrodes for Advanced
      Lithium-Ion Batteries.
AB  - The rational design and fabrication of electrode materials with desirable
      architectures and optimized properties has been demonstrated to be an effective
      approach towards high-performance lithium-ion batteries (LIBs). Although
      nanostructured metal oxide electrodes with high specific capacity have been
      regarded as the most promising alternatives for replacing commercial electrodes
      in LIBs, their further developments are still faced with several challenges such
      as poor cycling stability and unsatisfying rate performance. As a new class of
      binder-free electrodes for LIBs, self-supported metal oxide nanoarray electrodes
      have many advantageous features in terms of high specific surface area, fast
      electron transport, improved charge transfer efficiency, and free space for
      alleviating volume expansion and preventing severe aggregation, holding great
      potential to solve the mentioned problems. This review highlights the recent
      progress in the utilization of self-supported metal oxide nanoarrays grown on 2D
      planar and 3D porous substrates, such as 1D and 2D nanostructure arrays,
      hierarchical nanostructure arrays, and heterostructured nanoarrays, as anodes and
      cathodes for advanced LIBs. Furthermore, the potential applications of these
      binder-free nanoarray electrodes for practical LIBs in full-cell configuration
      are outlined. Finally, the future prospects of these self-supported nanoarray
      electrodes are discussed.

PMID- 27711260
TI  - Side-Gated In2O3 Nanowire Ferroelectric FETs for High-Performance Nonvolatile
      Memory Applications.
AB  - A new type of ferroelectric FET based on the single nanowire is demonstrated. The
      design of the side-gated architecture not only simplifies the manufacturing
      process but also avoids any postdeposition damage to the organic ferroelectric
      film. The devices exhibit excellent performances for nonvolatile memory
      applications, and the memory hysteresis can be effectively modulated by adjusting
      the side-gate geometries.

PMID- 27711261
TI  - High-Performance Non-Fullerene Organic Solar Cells Based on a Selenium-Containing
      Polymer Donor and a Twisted Perylene Bisimide Acceptor.
AB  - A novel polymer donor (PBDTS-Se) is designed to match with a non-fullerene
      acceptor (SdiPBI-S). The corresponding solar cells show a high efficiency of
      8.22%, which result from synergetic improvements of light harvesting, charge
      carrier transport and collection, and morphology. The results indicate that
      rational design of novel donor materials is important for non-fullerene organic
      solar cells.

PMID- 27711262
TI  - Toward Self-Powered Wearable Adhesive Skin Patch with Bendable Microneedle Array
      for Transdermal Drug Delivery.
AB  - A wearable adhesive skin patch for transdermal drug delivery is developed with
      bendable microneedles, dry adhesive and triboelectric energy harvester (TEH). The
      bendable microneedle array can overcome the needle breakage issue. The dry
      adhesive can realize a conformal attachment. The TEH can generate power when
      attached on flat skin or joint to power active components to be integrated in the
      future.

PMID- 27711263
TI  - A Safer Sodium-Ion Battery Based on Nonflammable Organic Phosphate Electrolyte.
AB  - Sodium-ion batteries are now considered as a low-cost alternative to lithium-ion
      technologies for large-scale energy storage applications; however, their safety
      is still a matter of great concern for practical applications. In this paper, a
      safer sodium-ion battery is proposed by introducing a nonflammable phosphate
      electrolyte (trimethyl phosphate, TMP) coupled with NaNi0.35Mn0.35Fe0.3O2 cathode
      and Sb-based alloy anode. The physical and electrochemical compatibilities of the
      TMP electrolyte are investigated by igniting, ionic conductivity, cyclic
      voltammetry, and charge-discharge measurements. The results exhibit that the TMP
      electrolyte with FEC additive is completely nonflammable and has wide
      electrochemical window (0-4.5 V vs. Na/Na+), in which both the Sb-based anode and
      NaNi0.35Mn0.35Fe0.3O2 cathode show high reversible capacity and cycling
      stability, similarly as in carbonate electrolyte. Based on these results, a
      nonflammable sodium-ion battery is constructed by use of Sb anode,
      NaNi0.35Mn0.35Fe0.3O2 cathode, and TMP + 10 vol% FEC electrolyte, which works
      very well with considerable capacity and cyclability, demonstrating a promising
      prospect to build safer sodium-ion batteries for large-scale energy storage
      applications.

PMID- 27711264
TI  - Cobalt Oxide and Cobalt-Graphitic Carbon Core-Shell Based Catalysts with
      Remarkably High Oxygen Reduction Reaction Activity.
AB  - The vital role of ethylenediaminetetraacetic acid on the structure and the oxygen
      reduction reaction activity of the non-precious-metal-based pyrolyzed catalyst is
      reported and elaborated. The resultant catalyst can overtake the performance of
      commercial Pt/C catalyst in an alkaline medium.

PMID- 27711266
TI  - Beyond Traditional RAFT: Alternative Activation of Thiocarbonylthio Compounds for
      Controlled Polymerization.
AB  - Recent developments in polymerization reactions utilizing thiocarbonylthio
      compounds have highlighted the surprising versatility of these unique molecules.
      The increasing popularity of reversible addition-fragmentation chain transfer
      (RAFT) radical polymerization as a means of producing well-defined, 'controlled'
      synthetic polymers is largely due to its simplicity of implementation and the
      availability of a wide range of compatible reagents. However, novel modes of
      thiocarbonylthio activation can expand the technique beyond the traditional
      system (i.e., employing a free radical initiator) pushing the applicability and
      use of thiocarbonylthio compounds even further than previously assumed. The
      primary advances seen in recent years are a revival in the direct photoactivation
      of thiocarbonylthio compounds, their activation via photoredox catalysis, and
      their use in cationic polymerizations. These synthetic approaches and their
      implications for the synthesis of controlled polymers represent a significant
      advance in polymer science, with potentially unforeseen benefits and
      possibilities for further developments still ahead. This Research News aims to
      highlight key works in this area while also clarifying the differences and
      similarities of each system.

PMID- 27711267
TI  - High-Performance Polymer Solar Cells Based on a Wide-Bandgap Polymer Containing
      Pyrrolo[3,4-f]benzotriazole-5,7-dione with a Power Conversion Efficiency of 8.63.
AB  - A novel donor-acceptor type conjugated polymer based on a building block of 4,8
      di(thien-2-yl)-6-octyl-2-octyl-5H-pyrrolo[3,4-f]benzotriazole-5,7(6H)-dione
      (TZBI) as the acceptor unit and 4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-benzo-[1,2
      b:4,5-b']dithiophene as the donor unit, named as PTZBIBDT, is developed and used
      as an electron-donating material in bulk-heterojunction polymer solar cells. The
      resulting copolymer exhibits a wide bandgap of 1.81 eV along with relatively deep
      highest occupied molecular orbital energy level of -5.34 eV. Based on the
      optimized processing conditions, including thermal annealing, and the use of a
      water/alcohol cathode interlayer, the single-junction polymer solar cell based on
      PTZBIBDT:PC71BM ([6,6]-phenyl-C71-butyric acid methyl ester) blend film affords a
      power conversion efficiency of 8.63% with an open-circuit voltage of 0.87 V, a
      short circuit current of 13.50 mA cm-2, and a fill factor of 73.95%, which is
      among the highest values reported for wide-bandgap polymers-based single-junction
      organic solar cells. The morphology studies on the PTZBIBDT:PC71BM blend film
      indicate that a fibrillar network can be formed and the extent of phase
      separation can be mani-pulated by thermal annealing. These results indicate that
      the TZBI unit is a very promising building block for the synthesis of wide
      bandgap polymers for high-performance single-junction and tandem (or
      multijunction) organic solar cells.

PMID- 27711265
TI  - A PCBM Electron Transport Layer Containing Small Amounts of Dual Polymer
      Additives that Enables Enhanced Perovskite Solar Cell Performance.
AB  - A polymer/PCBM hybrid electron transport layer is reported that enables high
      performance perovskite solar cells with a high power conversion efficiency of
      16.2% and with negligible hysteresis. Unlike previous approaches of reducing
      hysteresis by thermal annealing or fullerene passivation, the success of our
      approach can be mainly attributed to the doping of the PCBM layer using an
      insulating polymer (polystyrene) and an amine-containing polymeric semiconductor
      named PFNOX.

PMID- 27711268
TI  - Growth of Co Nanomagnet Arrays with Enhanced Magnetic Anisotropy.
AB  - A trigon structure formed by submonolayer gadolinium deposition onto Au(111) is
      revealed as a robust growth template for Co nanodot arrays. Scanning Tunneling
      Microscopy and X-Ray Magnetic Circular Dichroism measurements evidence that the
      Co nanoislands behave as independent magnetic entities with an out-of-plane easy
      axis of anisotropy and enhanced magnetic anisotropy values, as compared to other
      self-organized Co nanodot superlattices. The large strain induced by the lattice
      mismatch at the interface between Co and trigons is discussed as the main reason
      for the increased magnetic anisotropy of the nanoislands.

PMID- 27711269
TI  - Enhanced Ambient Stability of Efficient Perovskite Solar Cells by Employing a
      Modified Fullerene Cathode Interlayer.
AB  - A novel fullerene cathode interlayer is employed to facilitate the fabrication of
      stable and efficient perovskite solar cells. This modified fullerene surfactant
      significantly increases air stability of the derived devices due to its
      hydrophobic characteristics to enable 80% of the initial PCE to be retained after
      being exposed in ambient condition with 20% relative humidity for 14 days.

PMID- 27711270
TI  - Enantioselective synthesis of beta-substituted chiral allylic amines via Rh
      catalyzed asymmetric hydrogenation.
AB  - An asymmetric mono-hydrogenation of 2-acetamido-1,3-dienes catalyzed by a Rh
      DuanPhos complex has been developed. This approach provides easy access to chiral
      allylic amines with excellent enantioselectivities and high regioselectivities.
      The products are valuable chiral building blocks for pharmaceuticals.

PMID- 27711271
TI  - Surface-independent one-pot chelation of copper ions onto filtration membranes to
      provide antibacterial properties.
AB  - A one-pot method was developed for the chelation of copper ions onto the surface
      of filtration membrane to provide antibacterial properties. This simple,
      universal and cost-effective dopamine-Cu2+ approach provides a method of
      mitigating the long-term biofouling of surfaces.

PMID- 27711272
TI  - Intercalation-mediated nucleic acid nanoparticles for siRNA delivery.
AB  - Tremendous effort has been made to improve stability and delivery efficacy of
      small RNA therapeutics. However, nearly all current nano-encapsulation carriers
      utilize the critical balance between only two interacting parameters: RNA-binding
      electrostatic interactions and nanoparticle-stabilizing hydrophobic interactions.
      We report the development of intercalation-meditated nucleic acid (IMNA)
      nanoparticles, which utilize intercalation as a third interaction to enhance
      small RNA delivery. This toolbox expansion of interaction parameters may inspire
      the use of additional forces in nanoparticle drug carriers to increase potency
      and stability.

PMID- 27711273
TI  - Efficient nickel-catalyzed phosphinylation of C-S bonds forming C-P bonds.
AB  - The first nickel-catalyzed phosphinylation of C-S bonds forming C-P bonds is
      developed. This transformation can proceed readily with the simple Ni(cod)2 at a
      loading down to 0.1 mol% at the 10 mmol scale. A variety of aryl sulfur
      compounds, i.e. sulfides, sulfoxides and sulfones all couple with P(O)-H
      compounds to produce the corresponding organophosphorus compounds in high yields,
      which provides an efficient new method for the construction of C-P bonds.

PMID- 27711274
TI  - Vapour-induced solid-state C-H bond activation for the clean synthesis of an
      organopalladium biothiol sensor.
AB  - Room-temperature accelerated aging in the solid state has been applied for atom-
      and energy-efficient activation of either one or two C-H bonds of azobenzene and
      methyl orange by palladium(ii) acetate. Organopalladium complexes are prepared in
      quantitative reactions without potentially harmful side products.
      Dicyclopalladated methyl orange is water-soluble and is a selective chromogenic
      biothiol sensor at physiologically-relevant micromolar concentrations in buffered
      aqueous media.

PMID- 27711275
TI  - Supramolecular assembly of cobaloxime on nanoring-coated carbon nanotubes:
      addressing the stability of the pyridine-cobalt linkage under hydrogen evolution
      turnover conditions.
AB  - A carbon nanotube-cobaloxime nanohybrid was prepared through supramolecular
      assembly of tailored polymerizable amphiphiles, leading to the coordination of
      cobalt on pyridine-coated nanotubes. This material was used as a catalyst for
      hydrogen evolution in fully aqueous media. This study provides a definitive asset
      regarding the stability of the pyridine-cobalt axial bond under H2 evolution
      turnover conditions.

PMID- 27711276
TI  - Hierarchical silicalite-1 octahedra comprising highly-branched orthogonally
      stacked nanoplates as efficient catalysts for vapor-phase Beckmann rearrangement.
AB  - A triblock structure-directing agent was designed to synthesize hierarchical
      silicalite-1 octahedra comprising highly-branched, orthogonally-stacked and self
      pillared nanoplates that exhibited excellent and stable activity for the vapor
      phase Beckmann rearrangement of cyclic oximes and high lactam selectivity.

PMID- 27711277
TI  - The "chaperone" effect in microwave-driven reactions.
AB  - Chemically reactive molecules that are poor absorbers of microwave radiation can
      be selectively heated by the microwave and can experience chemical-rate
      enhancement if they are associated (agglomerated) in solution with non-reactive
      polar molecules that are strong microwave absorbers.

PMID- 27711278
TI  - The reductive aromatization of tridecacyclene.
AB  - The radical anion and dianion of tridecacyclene (C48H24, 1) have been prepared by
      reduction with potassium metal. Analysis of the solid-state structure of the
      dipotassium salt of the dianion (3) reveals evidence of increased aromatic
      character within the structure's central 8-membered ring despite preservation of
      the tub-like shape inherent to its neutral parent.

PMID- 27711279
TI  - Microsecond resolution of cavitation bubble dynamics using a high-speed
      electrochemical impedance approach.
AB  - A new method to detect the uncompensated resistance, the capacitance and the
      Faradaic current at an electrode exposed to ultrasonic cavitation is presented.
      The method enables these parameters to be resolved with a 2 microsecond
      resolution and relies on the detection of the impedance of an electrode recorded
      as a function of time with a suitable AC excitation signal (here 500 kHz). Data
      obtained from an aluminium electrode, held under potentiostatic control, is used
      to illustrate the technique with particular relevance to the effects of
      cavitation bubbles generated by ultrasound. Analysis of the data recorded shows
      that the cavitation bubbles form close to the surface of the electrode and
      collapse, causing damage to the passive film formed at the aluminium surface. The
      capacitance, uncompensated resistance and Faradaic signals are used to explore
      the dynamic processes and show expansion and collapse of bubbles prior to
      erosion/corrosion. The close proximity of the bubbles to the surface is deduced
      from the reductions in capacitance and increases in resistance prior to bubble
      collapse, which is then shown to trigger the onset of a Faradaic signal, thus
      confirming the erosion/corrosion mechanism previously assumed.

PMID- 27711280
TI  - A self-driven miniaturized liquid fuel cell.
AB  - We present a miniaturized fuel cell driven by an evaporation pump. The prototype
      cell shows a net peak current density of 22 mA cm-2 and a net power density of
      10.2 mW cm-2, both of which are the highest net values among passive-driven micro
      fuel cells.

PMID- 27711281
TI  - Palladium-catalyzed Mizoroki-Heck-type reactions of [Ph2SRfn][OTf] with alkenes
      at room temperature.
AB  - The first Pd-catalyzed Mizoroki-Heck-type reaction of [Ph2SRfn][OTf] with alkenes
      is described. The reaction of [Ph2SRfn][OTf] (Rfn = CF3, CH2CF3) with alkenes in
      the presence of 10 mol% Pd[P(t-Bu)3]2 and TsOH at room temperature provided the
      corresponding phenylation products in good to high yields. The bases that benefit
      the traditional Mizoroki-Heck reactions severely inhibited the transformation
      with [Ph2SRfn][OTf], whereas acids significantly improved the reaction. This
      protocol supplies a new class of cross-coupling partners for Mizoroki-Heck-type
      reactions and gains important insights into the reactivity of phenylsulfonium
      salts either with or without fluorine-containing alkyl groups as the promising
      phenylation reagents in organic synthesis.

PMID- 27711282
TI  - Synthesis and deposition of a Troger's base polymer on the electrode surface for
      potentiometric detection of a neuroblastoma tumor marker metabolite.
AB  - The development of novel diagnostic tools is a primary goal in bioanalytical
      chemistry. Here we report the synthesis of Troger's base functionalized with
      amino- and coumarin-units designed as a monomeric unit for the development of an
      electrochemical cancer sensor. The synthesized receptor was deposited onto a
      conducting support using electrochemical polymerization, characterized
      spectroscopically and tested potentiometrically towards metabolites used as tumor
      markers of neuroblastoma.

PMID- 27711283
TI  - Electrocatalytic hydrogen evolution using the MS2@MoS2/rGO (M = Fe or Ni) hybrid
      catalyst.
AB  - We established a three-tiered cake-like hybrid (MS2@MoS2/rGO, M = Fe or Ni) with
      the MS2 nanoparticles distributed over the platform of MoS2 and graphene
      (MoS2/rGO), which exhibits superior HER electrocatalytic activity as well as
      excellent electrochemical durability. The enhanced electrocatalytic activity
      benefits from the unique synergistic effects of graphene sheets enhancing the
      conductivity of the hybrid, MS2 (M = Fe or Ni) nanoparticles and MoS2 nanosheets
      providing abundant electrocatalytically active sites. Meanwhile, the mechanical
      stability is promoted by the meticulously-built cake-like structure.

PMID- 27711284
TI  - Asymmetric chlorination of 4-substituted pyrazolones catalyzed by natural
      cinchona alkaloid.
AB  - A natural quinidine-catalyzed asymmetric chlorination of 4-substituted
      pyrazolones is developed, affording products with a quaternary chiral chlorine
      attached carbon centre in high yield with excellent enantioselectivity. The low
      catalyst loading (1 mol%), broad substrate scope, and facile and valuable
      transformation of the product highlight the practical utility of this process.

PMID- 27711285
TI  - The plastic crystalline A15 phase of dimethylaminoalane, [N(CH3)2-AlH2]3.
AB  - A plastic crystalline phase of dimethylaminoalane has been discovered at T > 332
      K. The phase transitions solid - plastic phase - liquid are fully reversible. The
      plastic crystalline phase exhibits a cubic unit cell, space group Pm3[combining
      macron]n, in which the dimethylaminoalane molecules rotate and adopt a structural
      arrangement reminiscent of the A15 phase.

PMID- 27711286
TI  - Palladium catalyzed/silver tuned selective mono-/tetra-acetoxylation of o
      carboranes via B-H activation.
AB  - A palladium catalyzed/silver tuned selective mono- and tetra-acetoxylation of o
      carboranes has been developed, and a series of mono- and tetra-acetoxylated o
      carboranes decorated with active groups have been synthesized with moderate to
      good yields as well as excellent selectivity. A mechanism involving electrophilic
      palladation and cyclopalladation of the B-H bond was proposed.

PMID- 27711287
TI  - Multiphase separation of copper nanowires.
AB  - This communication reports a new method to purify copper nanowires with nearly
      100% yield from undesired copper nanoparticle side-products formed during batch
      processes of copper nanowire synthesis. This simple separation method can yield
      large quantities of long, uniform, high-purity copper nanowires to meet the
      requirements of nanoelectronics applications as well as provide an avenue for
      purifying copper nanowires in the industrial scale synthesis of copper nanowires,
      a key step for commercialization and application of nanowires.

PMID- 27711288
TI  - CuFeS2 colloidal nanocrystals as an efficient electrocatalyst for dye sensitized
      solar cells.
AB  - Cubic CuFeS2 nanocrystals (NCs) have been obtained via a facile colloidal
      chemistry approach and they show remarkable catalytic activity in the reduction
      of I3-. Dye sensitized solar cells (DSSCs) with CuFeS2 NCs as counter electrodes
      (CEs) display a power conversion efficiency of 8.10% comparable to that of a cell
      with Pt as the CE (7.74%) under the same conditions.

PMID- 27711289
TI  - Oxidation of hydroquinones by a (salen)ruthenium(vi) nitrido complex.
AB  - Hydroquinone is readily oxidized by a (salen)ruthenium(vi) nitrido complex in the
      presence of pyridine to give benzoquinone. Experimental and computational studies
      suggest that the reaction occurs via a novel mechanism that involves an initial
      electrophilic attack at the aromatic ring of the hydroquinone by the nitrido
      ligand.

PMID- 27711290
TI  - From ACQ to AIE: the suppression of the strong pi-pi interaction of naphthalene
      diimide derivatives through the adjustment of their flexible chains.
AB  - Unlike normal ACQ-to-AIE conversion by the introduction of aromatic rotors
      accompanying the realization of a twisted conformation and a prolonged pi-system,
      in this communication, the adjustment of the flexible chains can reach this point
      with the tunable packing modes while the original pi-system core and related
      properties of the aromatic naphthalene diimide remain nearly unchanged, providing
      an alternative approach for the inhibition of unwanted pi-pi stacking.

PMID- 27711291
TI  - Ion beam induced 18F-radiofluorination: straightforward synthesis of gaseous
      radiotracers for the assessment of regional lung ventilation using positron
      emission tomography.
AB  - A simple, straightforward and efficient method for the synthesis of [18F]CF4 and
      [18F]SF6 based on an ion beam-induced isotopic exchange reaction is presented.
      Positron emission tomography ventilation studies in rodents using [18F]CF4 showed
      a uniform distribution of the radiofluorinated gas within the lungs and rapid
      elimination after discontinuation of the administration.

PMID- 27711292
TI  - Nanocubic KTi2(PO4)3 electrodes for potassium-ion batteries.
AB  - Novel nanocubic KTi2(PO4)3 was successfully fabricated via a facile hydrothermal
      method combined with a subsequent annealing treatment and further evaluated as an
      electrode material for potassium-ion batteries for the first time. For
      comparison, carbon-coated KTi2(PO4)3 obtained by a normal cane sugar-assisted
      method reveals improved electrochemical performances in potassium-ion batteries.
      This work may give a new insight into developing electrode materials for
      potassium-ion batteries.

PMID- 27711293
TI  - When CMRP met alkyl vinyl ketone: visible light induced living radical
      polymerization (LRP) of ethyl vinyl ketone (EVK).
AB  - Photo responsive polyethyl vinyl ketone (PEVK) and various block copolymers were
      prepared through the visible light induced cobalt mediated radical polymerization
      (CMRP) process. The first order kinetics and linear increase in molecular weight
      with conversion demonstrated a well-behaved system. Chain extension experiments
      showed the retention of the living end of PEVK.

PMID- 27711294
TI  - Inhibition of TLR1/2 dimerization by enantiomers of metal complexes.
AB  - We report herein the identification of an immunomodulatory metal-based complex 1
      as a direct inhibitor of TLR1/2 heterodimerization. Both enantiomers of complex 1
      selectively suppressed TNF-alpha and TLR1/2 heterodimerization in Pam3CSK4
      induced macrophages, with Lambda-1 being more potent than Delta-1. Moreover, the
      complexes inhibited NF-kappaB transduction via the modulation of TLR1/2
      signaling. To our knowledge, complex 1 is the first metal-based inhibitor of
      TLR1/2 heterodimerization reported to date.

PMID- 27711295
TI  - Photodynamic micelles for amyloid beta degradation and aggregation inhibition.
AB  - Polymeric micelles loaded with chlorin e6 and Tanshinone I (TAS) were prepared
      and employed for photodegrading amyloid beta (Abeta) aggregates and inhibiting
      Abeta fibrillation.

PMID- 27711296
TI  - Crystals on the move: mechanical effects in dynamic solids.
AB  - When exposed to external stimuli such as heat or light, certain single crystals
      can acquire momentum and undergo motion. On a molecular scale, the motility of
      such dynamic single crystals is triggered by a phase transition or chemical
      reaction without gaseous products, and macroscopically manifests as either slow
      (reversible or irreversible) deformation, or as rapid, almost instantaneous
      propulsion of the crystals that is oftentimes accompanied by disintegration.
      While the elastic energy of the slow reconfiguration processes such as bending,
      twisting and coiling can be utilized for actuation of other objects, the fast
      disintegrative processes could be exploited to initiate pressure-sensitive
      applications. This short review intends to summarize recent developments in the
      growing research on dynamic crystals, especially aspects of the mechanism of
      rapid motion of thermosalient and photosalient (leaping) crystals. The collective
      evidence indicates that these solids are organic-based analogues of the inorganic
      martensitic materials. While qualitative explanation of the molecular processes
      that lead to the related dynamic phenomena can be provided, quantification of
      their kinematics, estimation of the useful work that can be extracted, and
      prediction of their occurrence are yet to be established. Harnessing the
      potential of these materials to rapidly and efficiently perform the fundamentally
      important process of transduction of heat or light into kinetic energy appears as
      a prospective basis for their application in motion gears and devices.

PMID- 27711297
TI  - Nitrogen-doped hollow carbon spheres with a wrinkled surface: their one-pot
      carbonization synthesis and supercapacitor properties.
AB  - Nitrogen-doped hollow carbon spheres with a wrinkled surface were rationally
      synthesized for the first time by using graphene oxide as a morphology
      controlling agent through direct pyrolysis of core-shell structured GO
      resol@melamine formaldehyde composites, showing excellent rate performance
      towards supercapacitors, due to their unique structural and surface properties.

PMID- 27711298
TI  - Visible-light-mediated generation of nitrile oxides for the photoredox synthesis
      of isoxazolines and isoxazoles.
AB  - Visible-light photoredox catalysis enables the synthesis of biologically relevant
      isoxazolines and isoxazoles from hydroxyimino acids. The process shows broad
      functional group compatibility and mechanistic and computational studies support
      a visible-light-mediated generation of nitrile oxides by two sequential oxidative
      single electron transfer processes.

PMID- 27711299
TI  - Light-induced spatial separation of charges toward different crystal facets of
      square-like WO3.
AB  - Light-induced preferential migration of electrons and holes to the minor (200)
      and (020) facets and the dominant (002) facets of square-like WO3, respectively,
      resulted in the square-like WO3 nanoplates with Pt loaded mainly on dominant
      (002) facets shows higher photocatalytic activity than that Pt loaded on the
      minor facets.

PMID- 27711300
TI  - Organocatalyzed nucleophilic addition of pyrazoles to 2H-azirines: asymmetric
      synthesis of 3,3-disubstituted aziridines and kinetic resolution of racemic 2H
      azirines.
AB  - The first organocatalytic asymmetric nucleophilic addition of arylpyrazoles to 2H
      azirines and kinetic resolution of racemic 2H-azirines have been realized. Chiral
      aziridines were obtained with up to 98% yields and up to 99.9% ee. Meanwhile,
      simply changing the ratio of reactants, optically active 2H-azirines were
      recovered in good yields with excellent enantioselectivities.

PMID- 27711301
TI  - Organocatalytic asymmetric [3+2] cycloaddition of N-2,2,2-trifluoroethylisatin
      ketimines with 3-alkenyl-5-arylfuran-2(3H)-ones.
AB  - A highly diastereo- and enantioselective [3+2] cycloaddition reaction of N-2,2,2
      trifluoroethylisatin ketimines and 3-alkenyl-5-arylfuran-2(3H)-ones was developed
      with 1 mol% thiourea-tertiary amine as the catalyst. A series of spiro[pyrrolidin
      3,2'-oxindoles] bearing four consecutive stereocenters, including two vicinal
      spiro-quaternary chiral centers, were efficiently obtained with excellent results
      (up to >99% yield, >20 : 1 dr, and >99% ee).

PMID- 27711302
TI  - Structure-controlled polymers prepared by pseudo-living addition-condensation
      polymerization and their application to light harvesting.
AB  - An A,B-block amphiphilic polymer and a branched polymer were prepared by using a
      new type of pseudo-living addition-condensation polymerization. The first polymer
      showed an interphase photoinduced energy transfer in a micellar system, while the
      second type showed efficient light-harvesting ability.

PMID- 27711303
TI  - Asymmetric block copolymer membranes with ultrahigh porosity and hierarchical
      pore structure by plain solvent evaporation.
AB  - Membranes with a hierarchical porous structure could be manufactured from a block
      copolymer blend by pure solvent evaporation. Uniform pores in a 30 nm thin skin
      layer supported by a macroporous structure were formed. This new process is
      attractive for membrane production because of its simplicity and the lack of
      liquid waste.

PMID- 27711304
TI  - Guanidiniocarbonyl pyrrole (GCP) conjugated PAMAM-G2, a highly efficient vector
      for gene delivery: the importance of DNA condensation.
AB  - A novel hybrid compound 1 efficiently shuttles genetic material into HeLa cells
      at concentrations as low as 0.6 MUM, whereas the parent compound PAMAM-G2 is
      ineffective even at 200 MUM. The high efficiency of 1 stems from its capabiliy to
      form highly condensed ligand-DNA polyplexes. Its binding affinity is actually
      lower than for the parent dendrimer. Compound 1 is even 200 times more effective
      and less cytotoxic than PEI, the current gold standard in gene transfection with
      cationic polymers.

PMID- 27711305
TI  - Fast preparation of ultrafine monolayered transition-metal dichalcogenide quantum
      dots using electrochemical shock for explosive detection.
AB  - A simple, general and fast method called "electrochemical shock" is developed to
      prepare monolayered transition-metal dichalcogenide (TMD) QDs with an average
      size of 2-4 nm and an average thickness of 0.85 +/- 0.5 nm with only about 10 min
      of ultrasonication. Just like nails hammered into a plate, the electrochemical
      shock with Al3+ ions and the following extraction with the help of oleic acid can
      disintegrate bulk TMD crystals into ultrafine TMD QDs. The fast-prepared QDs are
      then applied to detect highly explosive molecules such as 2,4,6-trinitrophenol
      (TNP) with a low detection limit of 10-6 M. Our versatile method could be broadly
      applicable for the fast production of ultrathin QDs of other materials with great
      promise for various applications.

PMID- 27711306
TI  - Enhancement of magnetic anisotropy in a Mn-Bi heterobimetallic complex.
AB  - A novel Mn2+Bi3+ heterobimetallic complex, featuring the closest MnBi interaction
      for a paramagnetic molecular species, exhibits unusually large axial zero-field
      splitting. We attribute this enhancement to the proximity of Mn2+ to a heavy main
      group element, namely, bismuth.

PMID- 27711308
TI  - Regioselective synthesis of multisubstituted 1,2,3-triazoles: moving beyond the
      copper-catalyzed azide-alkyne cycloaddition.
AB  - Copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) is an essential "click
      chemistry" reaction that is widely used in chemical biology, medicinal chemistry
      and materials science. The CuAAC reaction of terminal alkynes provides a mild and
      efficient synthesis of 1,4-disubstituted 1,2,3-triazoles. However, the click
      reaction of internal alkynes with azides, giving trisubstituted triazoles, is
      very challenging. This feature article highlights the recent progress addressing
      this fundamental problem. Particular emphasis is on the current and emerging
      strategies to introduce functional groups to the C-5 position of triazoles in a
      regioselective manner.

PMID- 27711307
TI  - Electrophoresis separation assisted G-quadruplex DNAzyme-based chemiluminescence
      signal amplification strategy on a microchip platform for highly sensitive
      detection of microRNA.
AB  - We have developed an electrophoresis separation assisted G-quadruplex DNAzyme
      based chemiluminescence (CL) signal amplification strategy on a microchip
      platform for the detection of trace microRNA. This strategy exhibits high
      sensitivity and specificity for detection of target molecules.

PMID- 27711310
TI  - Morphology and phase transformation from NaCaSiO3OH to Na2Ca2Si2O7 and
      photoluminescence evolution via Eu3+/Tb3+ doping.
AB  - A facile and controllable ethanol/water aided hydrothermal process was developed
      to prepare the NaCaSiO3OH:Tb3+/Eu3+ phosphor. The morphologies were in situ
      constructed with the phase transformation from NaCaSiO3OH to Na2Ca2Si2O7, and the
      intrinsic crystal structural transformation mechanism and the dependence of their
      photoluminescence tuning on the Tb3+/Eu3+ ratio have been discussed.

PMID- 27711309
TI  - EXAFS reveals two Mo environments in the nitrogenase iron-molybdenum cofactor
      biosynthetic protein NifQ.
AB  - Mo and Fe K-edge EXAFS analysis of NifQ shows the presence of a [MoFe3S4] cluster
      and a second independent Mo environment that includes Mo-O bonds and Mo-S bonds.
      Both environments are relevant to FeMo-co biosynthesis and may represent
      different stages of Mo biochemical transformations catalyzed by NifQ.

PMID- 27711312
TI  - Simple rules and the emergence of complexity in surface chirality.
AB  - Surface chirality arising from self-organized molecular monolayers may manifest
      both a handedness and footedness, leading to a dual level of chiral expression.
      Recent advances have determined both levels of chirality at the single-molecule
      level and, surprisingly, reveal a plethora of chiral orderings. There is yet no
      clear understanding of why such varied manifestations of interface chirality
      occur. Here, we show that the ordering of handedness and footedness of amino
      acids within (n* 2) assemblies on Cu(110) may be understood on the basis of three
      simple generic rules from which a variety chiral expressions naturally arise.
      These rules also provide insights into how enantiomer assembly at surfaces may be
      tailored to produce required chiral organizations and segregations.

PMID- 27711311
TI  - Synthesis and photophysical properties of C3-symmetric tris(pyridyl)truxene
      scaffolds of Ru(ii) and Re(i).
AB  - Facial Ru(ii)- and Re(i)-complexes of a novel face-capping tris(pyridyl)truxene
      ligand were synthesised and characterised by various analytical techniques
      including single crystal XRD. The Ru(ii) complex exhibits unusual green
      phosphorescence with a long excited-state lifetime.

PMID- 27711313
TI  - Porous cobalt-iron nitride nanowires as excellent bifunctional electrocatalysts
      for overall water splitting.
AB  - Designing highly active, earth-abundant and stable bifunctional electrocatalysts
      for both the oxygen (OER) and hydrogen (HER) evolution reactions is very crucial
      to overall water splitting. Herein, we developed nanoparticle-stacked porous
      Co3FeNx (NSP-Co3FeNx) nanowires as bifunctional electrocatalysts, exhibiting
      excellent OER and HER activity with a low overpotential of 222 mV at 20 mA cm-2
      and 23 mV at 10 mA cm-2, respectively, due to their unique structural advantages
      with grain boundaries, defects and dislocations. Moreover, the electrocatalysts
      as bifunctional electrodes show a high performance with 10 mA cm-2 at a cell
      voltage of 1.539 V.

PMID- 27711314
TI  - Synthesis of 2,3-allenylamides utilizing [1,2]-phospha-Brook rearrangement and
      their application to gold-catalyzed cycloisomerization providing 2-aminofuran
      derivatives.
AB  - An efficient synthetic method for 2,3-allenylamides having an oxygen
      functionality at the 2-position, which are difficult to access by conventional
      methods, was newly developed by utilizing the [1,2]-phospha-Brook rearrangement
      under Bronsted base catalysis. Further manipulation of the 2,3-allenylamides via
      gold-catalyzed cycloisomerization enables the formation of 2-aminofuran
      derivatives.

PMID- 27711315
TI  - Zinc-substituted ZIF-67 nanocrystals and polycrystalline membranes for
      propylene/propane separation.
AB  - Continuous ZIF-67 polycrystalline membranes with effective propylene/propane
      separation performances were successfully fabricated through the incorporation of
      zinc ions into the ZIF-67 framework. The separation factor increases from 1.4 for
      the pure ZIF-67 membrane to 50.5 for the 90% zinc-substituted ZIF-67 membrane.

PMID- 27711316
TI  - Photo-powered stretchable nano-containers based on well-defined vesicles formed
      by an overcrowded alkene switch.
AB  - A novel photo-responsive nano-container was successfully constructed based on
      well-defined vesicles formed by an amphiphilic overcrowded alkene switch. The
      nano-container could adjust its inner volume in reversible photo/heat controlled
      mode, which could show potential in remote drug delivery systems.

PMID- 27711317
TI  - Constructing luminescent particle/MOF composites by employing
      polyvinylpyrrolidone-modified organic crystals as seeds.
AB  - We develop a novel and facile chemical reaction route to modulate the
      crystallization process of luminescent zinc 8-hydroxyquinoline (Znq2) particles.
      Polyvinylpyrrolidone (PVP)-modified octahedral Znq2 micro- and nano-crystals were
      used as seeds to construct two distinct hybrid structures, i.e., Znq2@ZIF-8 core
      shell and multiple Znq2 particles on each ZIF-8.

PMID- 27711318
TI  - Capsule-bowl conversion triggered by a guest reaction.
AB  - A new M20L8 coordination capsule was synthesized. Owing to the structural
      flexibility and dynamic properties, the capsule showed wide scope for guest
      encapsulation. Furthermore, unique capsule-bowl conversion occurred upon a large
      guest encapsulation or a guest reaction.

PMID- 27711319
TI  - Copper-catalyzed N-thioetherification of sulfoximines using disulfides.
AB  - A novel copper-catalyzed N-thioetherification of sulfoximines under mild reaction
      conditions was developed. In this procedure, the N-S bond formation was achieved
      using readily available disulfides as the sulfur source.

PMID- 27711320
TI  - Enantioselective construction of branched 1,3-dienyl substituted quaternary
      carbon stereocenters by asymmetric allenyl Claisen rearrangement.
AB  - The availability of enantiomerically enriched 1,3-dienyl substituted quaternary
      stereocenters is highly valuable for the synthesis of complex natural compounds.
      Despite great advances in the area of construction of alkenyl-substituted types,
      a general, practical catalytic system that works for enantioselective formation
      of 1,3-diene derivatives still remains to be developed. Herein, we disclose the
      first asymmetric Claisen rearrangement of allenyl vinyl ethers to access
      optically active beta-ketoesters, containing branched 1,3-butadienyl substituted
      stereocenters. A variety of substrates bearing a range of useful functional
      groups were well tolerated, thus affording the corresponding products with
      excellent enantioselectivities (up to 99% ee) and high yields (up to 91%).

PMID- 27711321
TI  - A solid state highly emissive Cu(i) metallacycle: promotion of cuprophilic
      interactions at the excited states.
AB  - The straightforward synthesis of a new Cu(i) metal-rich small metallacycle is
      presented. This compound is luminescent in the solid state with an emission
      quantum yield of 72% at room temperature and displays a pronounced reversible red
      shift of its emission spectra upon cooling. Quantum chemical calculations reveal
      that these properties are governed by important geometrical relaxations that
      imply the formation of cuprophilic interactions at the excited states.

PMID- 27711322
TI  - Conductive magnetic-patchy colloidal microparticles for a high performance
      pressure sensor.
AB  - A robust and straightforward approach for fabrication of a new type of colloidal
      pressure sensor was proposed. For this purpose, we synthesized uniform conductive
      magnetic-patchy microparticles using a microfluidic technique and then coated
      them with poly(3,4-ethylene dioxythiophene)-poly(styrene sulfonate) layers using
      the layer-by-layer deposition. Finally we showed that the magnetic-patchy
      conductive microparticles could be positioned on the target sites while precisely
      detecting pressure changes with excellent sensitivity.

PMID- 27711323
TI  - Embedding magnetic nanoparticles into coordination polymers to mimic zinc ion
      transporters for targeted tumor therapy.
AB  - Magnetic nanoparticle-embedded coordination polymers could act as mimics for zinc
      ion transporters for targeted cancer therapy. Compared with traditional zinc
      ionophores, our system could realize targeted and internal environment responsive
      transport of zinc ions to suppress the tumour growth while minimizing nonspecific
      injury to normal tissues.

PMID- 27711324
TI  - Ion mobility separation of deprotonated oligosaccharide isomers - evidence for
      gas-phase charge migration.
AB  - There has been increasing evidence that certain isomeric glycans can be separated
      efficiently by ion mobility-mass spectrometry when deprotonated ions are
      analyzed. To better understand the fundamentals behind these separations, we here
      investigate the impact of ionisation mode and adduct formation using IM-MS,
      density-functional theory and ab initio molecular dynamics.

PMID- 27711325
TI  - Supramolecular metallogels with bulk self-healing properties prepared by in situ
      metal complexation.
AB  - In this feature article, we discuss a series of contributions dealing with the in
      situ fabrication of supramolecular metallogels (i.e. using low molecular weight
      ligands and metal ions) that show self-healing properties of the bulk gel phase
      after complete physical segregation. Most of the advances in this area have taken
      place during the last three years and are mainly represented by organogels,
      whereas examples of hydrogels and organic-aqueous gels are still a minority. In
      situ gelation via metal-coordination of low molecular weight compounds is
      conceptually different from the use of premade (e.g. in solution) coordination
      polymers and polymeric structures as gelators and ligands, respectively. In the
      case of in situ gelation, the cooperative effects of all components of the
      mixture (i.e. ligand, metal ion, counterions and solvent molecules) in an
      appropriate ratio under well-defined experimental conditions play a crucial role
      in the gelation phenomenon and self-healing properties of the material.

PMID- 27711326
TI  - A chiral pool approach for asymmetric syntheses of (-)-antrocin, (+)-asperolide
      C, and (-)-trans-ozic acid.
AB  - Ozonolysis of aromatic abietane (+)-carnosic acid (4) is used to create an
      important intermediate in an enantiomerically pure form, resulting in a simple,
      concise, readily scalable, and asymmetric synthesis of (-)-antrocin (1). This
      strategy not only provides an efficient approach to (-)-antrocin (1) synthesis
      but can also be readily adopted for the syntheses of optically pure (+)
      asperolide C (2) and (-)-trans-ozic acid (3) from the naturally abundant aromatic
      abietanes (+)-podocarpic acid (5) and (+)-dehydroabietic acid (6). The strategy
      presented here is an example of the use of naturally occurring aromatic abietanes
      as a chiral pool and offers an account of the asymmetric synthesis of terpenoids.

PMID- 27711327
TI  - The memory-driven order-disorder transition of a 3D-supramolecular architecture
      based on calix[5]arene and porphyrin derivatives.
AB  - A 3D supramolecular polymer based on calix[5]arene tethered poly(p
      phenyleneethynylene) with a complementary porphyrin endowed with
      alkanediyldiammonium functions is prepared in solution but collapses when
      transferred to a chemically inert solid matrix forming a dispersion of de-phasing
      porphyrin aggregates. We found that a short thermal shock induces the de
      aggregation of the porphyrin aggregates, and a partial restoration of the
      original 3D-supramolecular architecture.

PMID- 27711328
TI  - Dual-functional hard template directed one-step formation of a hierarchical
      porous carbon-carbon nanotube hybrid for lithium-sulfur batteries.
AB  - A novel hierarchical porous carbon-carbon nanotube hybrid (HPCC) is prepared
      using a one-step strategy that uses nickel nanoparticles as the template for pore
      formation and at the same time, as the catalyst for carbon nanotube (CNT) growth.
      Such a structure can not only store sulfur in the micro- and mesopores, which
      restrict the shuttling of polysulfides, but also ensure good electrical
      conductivity of the whole system due to the incorporation of CNTs. The
      hierarchical porous structure also ensures fast mass transportation. These
      factors effectively guarantee the high electrochemical performance of sulfur
      stored in this carbon in lithium-sulfur batteries.

PMID- 27711329
TI  - Creation of new guest accessible space under gas pressure in a flexible MOF:
      multidimensional insight through combination of in situ techniques.
AB  - Metal-organic frameworks (MOFs) are an important class of porous materials with
      numerous potential applications. Molecular level understanding of various
      processes involving MOFs is very important in order to design porous materials
      with improved properties. Here we describe the elucidation by means of single
      crystal X-ray diffraction (SCD) of three different phases of Zn2(bdc)2(bpy) at
      different pressures of CO2. Moreover, this is a rare example where new space is
      created in the structure under gas pressure - space that was not previously
      occupied by guest molecules in any of the related structures. In addition to in
      situ SCD and sorption analysis, pressure-gradient differential scanning
      calorimetry (PG-DSC) provides very useful information about the system. This
      study represents the first instance where PG-DSC has been used to study the
      sorption behavior of a flexible porous framework.

PMID- 27711330
TI  - Anion size control of the packing in the metallic versus semiconducting chiral
      radical cation salts (DM-EDT-TTF)2XF6 (X = P, As, Sb).
AB  - Control of the structural type in metallic enantiopure and racemic radical cation
      salts is achieved through hydrogen bonding interactions between the chiral donor
      DM-EDT-TTF and the XF6 anions (X = P, As, Sb), determined by the anion size and
      the chiral information.

PMID- 27711331
TI  - Nitrogen-doped carbon dots with excitation-independent long-wavelength emission
      produced by a room-temperature reaction.
AB  - Nitrogen-doped carbon dots (CDs) have been produced by a new facile "bottom-up"
      synthesis, using the room-temperature reaction between acetonitrile and sodium
      naphthalene. The obtained hydrophobic CDs are monodisperse (~2.6 nm) and present
      an excitation-independent emission at ~588 nm with a small full width at half
      maximum (FWHM) of ~52 nm. The CDs can be simply modified to be hydrosoluble and
      have been demonstrated to be an efficient red-emission agent for both in vivo and
      in vitro bioimaging.

PMID- 27711332
TI  - Tandem triggering of wormlike micelles using CO2 and redox.
AB  - Wormlike micelles constructed from a selenium-containing surfactant and a
      commercial diamine through a simple combination strategy can reversibly undergo a
      tandem reaction in response to CO2 and redox, exhibiting a transition between a
      gel-like fluid and a water-like fluid due to the evolution of aggregate
      structures from wormlike micelles to spherical micelles.

PMID- 27711333
TI  - Robust onionlike structures with magnetic and photodynamic properties formed by a
      fullerene C60-POM hybrid.
AB  - We report for the first time the synthesis of a covalently-linked fullerene C60
      Dawson POM hybrid, which can form onionlike structures with rich magnetic,
      electrochemical and photodynamic properties.

PMID- 27711334
TI  - Kinetically controlled simplification of a multiresponsive [10 * 10] dynamic
      imine library.
AB  - Kinetically controlled self-sorting processes in complex synthetic mixtures
      represent an important model for behaviours of biological networks, which operate
      far from equilibrium and without interference among simultaneous metabolic
      pathways. However, most of the previously reported kinetic self-sorting protocols
      dealt with small dynamic libraries and a single external stimulus. Here, we
      report the iterative simplification of a large imine dynamic combinatorial
      library (DCL) constructed from 10 aldehydes and 10 anilines, under the sequential
      influence of an oxidant, an adsorbent, and an increase in temperature. Six
      components of this initial DCL are mechanically isolated and amplified at least
      three-fold relative to their equilibrium distributions at the outset of the
      sorting process.

PMID- 27711335
TI  - Polycyclic aromatic hydrocarbons with orthogonal tetraimides as n-type
      semiconductors.
AB  - Two new polycyclic aromatic hydrocarbons with orthogonal imide groups have been
      synthesized and characterized. These semiconductors have strong electron
      affinities with an electron mobility of up to 1.75 cm2 V-1 s-1 in solution
      processed single-crystalline microfibers.

PMID- 27711336
TI  - Traceless directing group mediated branched selective alkenylation of unbiased
      arenes.
AB  - Owing to the synthetic importance of branched olefinated products, we report
      palladium catalyzed formation of branched olefins facilitated by a C-H activation
      based protocol. This involves selective insertion of olefins and subsequent
      decarboxylation using a completely unbiased benzene ring as the starting
      precursor. The significance of the protocol has been further highlighted by
      exhibition of functionality tolerance along with a late-stage modification of the
      branched olefinated products leading to the formation of other functionalized
      molecules.

PMID- 27711337
TI  - Br2F7- and Br3F10-: peculiar anions showing MU2- and MU3-bridging F-atoms.
AB  - RbCl and CsCl react with BrF3 yielding the corresponding
      decafluoridotribromates(iii), MBr3F10 (M = Rb, Cs), which were structurally
      characterized for the first time. The Br3F10- anion is surprisingly not linear
      but contains a MU3-bridging fluorine atom and seems to be the first example of
      MU3-F bridging of Br atoms. The compounds are highly reactive and cannot be
      handled in glassware. As for the tetrafluoridobromates themselves, they are
      powerful oxidizers and thus suitable for the dry-chemical recycling of precious
      metals and additionally feature a significantly higher BrF3 content.

PMID- 27711338
TI  - Magnesium plasmonics for UV applications and chiral sensing.
AB  - We demonstrate that chiral magnesium nanoparticles show remarkable plasmonic
      extinction- and chiroptical-effects in the ultraviolet region. The Mg nanohelices
      possess an enhanced local surface plasmon resonance (LSPR) sensitivity due to the
      strong dispersion of most substances in the UV region.

PMID- 27711339
TI  - Liquid-liquid extraction of enzymatically synthesized functional RNA
      oligonucleotides using reverse micelles with a DNA-surfactant.
AB  - We successfully implemented solvent extraction of short, single-stranded RNA
      using reverse micelles (water-in-oil microemulsions) with a DNA-surfactant. A
      thrombin-binding RNA aptamer was enzymatically synthesized and purified by
      extraction using the reverse micellar system. The extracted RNA aptamer retained
      thrombin-binding activity after the extraction procedure.

PMID- 27711340
TI  - Electrodeposited Fe and Fe-Au nanowires as MRI contrast agents.
AB  - Electrodeposited Fe and Fe-Au nanowires were studied for potential as MRI
      contrast agents, especially for T2-weighted imaging. Transverse relaxivities up
      to r2 = 77.1 mM Fe-1 s-1 (at 1.5 T) were achieved when Fe-Au nanowires were
      coated with thiol and carboxylic acid functionalized poly(ethyleneglycol). T2
      Weighted images (9 T) verified successful contrast.

PMID- 27711341
TI  - Steric hindrance inhibition of strand displacement for homogeneous and signal-on
      fluorescence detection of human serum antibodies.
AB  - Based on a new steric hindrance inhibition of the DNA strand displacement
      strategy, we report the design of a robust fluorescence signal-on method for
      homogeneous and sensitive detection of antibodies from human serum samples. Such
      a steric hindrance effect leads to sensitive detection of the target antibodies
      with a detection limit of 5.6 nM. In addition, the developed sensing approach
      shows high selectivity against other interference proteins and the detection of
      the target antibodies in human sera by this method is also verified.

PMID- 27711342
TI  - A carborane-triggered metastable charge transfer state leading to spontaneous
      recovery of mechanochromic luminescence.
AB  - An efficient strategy was designed to realize spontaneous recovery of
      mechanochromic luminescence by carborane-functionalized anthracene derivatives. A
      metastable charge-transfer emission from anthracene to o-carborane is responsible
      for this process.

PMID- 27711343
TI  - S(vi) Lewis acids: fluorosulfoxonium cations.
AB  - Avenues to S-based Lewis acids were developed via the oxidation of aryl
      sulfoxides with XeF2, giving difluorodiarylsulfoxides which react via fluoride
      abstraction to afford Lewis acidic fluorosulfoxonium cations; this acidity is
      derived from the S-F sigma* orbital and has been probed both experimentally and
      computationally.

PMID- 27711344
TI  - Catalytic reduction of amides to amines by electrophilic phosphonium cations via
      FLP hydrosilylation.
AB  - A catalytic methodology for the conversion of amides to amines is reported. Of
      the 25 examples described, 14 examples involve the reduction of N
      trifluoroacetamides to the corresponding trifluoroethylamines. These reductions
      are achieved by catalytic hydrosilylation of the amide mediated by an
      electrophilic phosphonium cation (EPC) catalyst.

PMID- 27711345
TI  - Single-step preparation of indium tin oxide nanocrystals dispersed in ionic
      liquids via oxidation of molten In-Sn alloys.
AB  - Oxidation of molten In-Sn alloys was carried out in ionic liquids by heat
      treatment with vigorous stirring, resulting in the formation of indium tin oxide
      (ITO) nanocrystals. The ITO nanocrystals exhibited a plasmon peak, the peak
      wavelength of which was blue-shifted with an increase in the Sn fraction in ITO.

PMID- 27711346
TI  - Construction of the carbon-chalcogen (S, Se, Te) bond at the 2,6-positions of
      BODIPY via Stille cross-coupling reaction.
AB  - Seven new 2-chalcogen- or 2,6-dichalcogen- (S, Se, Te) BODIPY derivatives were
      synthesized in good to excellent yields (55-95%) by a Pd-catalyzed C-heteroatom
      Stille cross-coupling reaction, overcoming the limitations of SNAr. The
      fluorophores show interesting tunable optical properties associated with the
      formation of a twisted intramolecular charge transfer excited state and competing
      intersystem crossing.

PMID- 27711347
TI  - Multi-color polymer pen lithography for oligonucleotide arrays.
AB  - Multi-color patterning by polymer pen lithography (PPL) was used to fabricate
      covalently immobilized fluorophore and oligonucleotide arrays with up to five
      different components. The oligonucleotide arrays offer a virtually unlimited
      inventory of orthogonal binding tags for self-assembly of proteins as
      demonstrated by use of the arrays to monitor cell-protein interactions of MCF7
      cells.

PMID- 27711348
TI  - A photo-responsive metallomesogen for an optically and electrically tunable
      polarized light modulator.
AB  - A palladium(ii)-based metallomesogen with azobenzene was synthesized for the
      fabrication of an optically and electrically tunable polarized light modulator.
      Owing to the extended molecular geometry constructed by organometallic chemistry,
      the photo-responsive metallomesogen showed an excellent orientation in liquid
      crystal media.

PMID- 27711349
TI  - Caging the uncageable: using metal complex release for photochemical control over
      irreversible inhibition.
AB  - Photochemical control over irreversible inhibition was shown using Ru(ii)-caged
      inhibitors of cathepsin L. Levels of control were dependent on where the Ru(ii)
      complex was attached to the organic inhibitor, reaching >10 : 1 with optimal
      placement. A new strategy for photoreleasing Ru(ii) fragments from inhibitor
      enzyme conjugates is also reported.

PMID- 27711350
TI  - A general and versatile fluorescence turn-on assay for detecting the activity of
      protein tyrosine kinases based on phosphorylation-inhibited tyrosyl oxidation.
AB  - A simple, homogeneous and generic method for detecting protein tyrosine (Tyr)
      kinase activity is developed based on a tyrosinase-assisted fluorescence turn-on
      strategy. The tyrosinase-mediated oxidation of the Tyr residue in a fluorescently
      labeled peptide may lead to efficient fluorescence quenching, while the tyrosine
      kinase-catalyzed phosphorylation of the peptide can prevent the Tyr oxidation and
      thus maintain strong fluorescence.

PMID- 27711351
TI  - Superior electrochemical performance of N-doped nanocrystalline FeF3/C with a
      single-step solid-state process.
AB  - FeF3 is a promising cathode material for lithium ion batteries but its poor
      electronic conductivity makes it non-practical. Here, we significantly improve
      the electrochemical activity of FeF3 by reducing the strong ionic character of Fe
      F with the replacement of some F with N atoms. N-doped nanocrystalline FeF3/C
      achieves the best electrochemical performance among FeF3 compounds reported to
      date: ~95 mA h g-1 at 21.1C discharge rate for 250 cycles. The results illustrate
      that the poor electronic conductivity of metal fluorides can be controlled by
      doping and this enables FeF3 or metal fluorides to be practically utilized in
      possible applications including energy conversion and storage.

PMID- 27711352
TI  - Micro-Cu4I4-MOF: reversible iodine adsorption and catalytic properties for tandem
      reaction of Friedel-Crafts alkylation of indoles with acetals.
AB  - We report a convenient approach, the first of its kind, to construct a microscale
      non-metal@MOF composite catalytic host-guest system for an organic tandem
      reaction. The reported porous Cu4I4-MOF is able to reversibly adsorb molecular
      iodine at room temperature. The obtained I2@Cu4I4-MOF host-guest system can be a
      highly heterogeneous catalyst to promote the Friedel-Crafts alkylation of indoles
      with acetals in a one-pot two-step fashion under solvent-free conditions at room
      temperature.

PMID- 27711353
TI  - Spatially well-defined carbohydrate nanoplatforms: synthesis, characterization
      and lectin interaction study.
AB  - Two novel dodecasubstituted carbohydrate nanoplatforms based on molecular
      Borromean rings and dodecaamine cages have been prepared for use in evaluating
      the importance of the spatial distribution of carbohydrates in their interaction
      with lectins. The binding affinities of the glyconanoplatforms were characterized
      using quartz crystal microbalance technology and compared with a monovalent
      reference and dodecaglycosylated fullerenes.

PMID- 27711354
TI  - Radical trideuteromethylation with deuterated dimethyl sulfoxide in the synthesis
      of heterocycles and labelled building blocks.
AB  - The potential of deuterated pharmaceuticals is being widely demonstrated. Here we
      describe the first trideuteromethylation under radical reaction conditions using
      deuterated dimethyl sulfoxide as a reagent for the synthesis of labelled
      heterocycles and trideuteromethylated compounds. A broad scope of the developed
      method for the synthesis of various scaffolds was demonstrated.

PMID- 27711355
TI  - A bioorthogonal approach for imaging the binding between Dasatinib and its target
      proteins inside living cells.
AB  - Herein, we present a simple readout of the binding between a chemical drug and
      its target proteins in the cytoplasm by using a two-step bioorthogonal labeling
      method combined with spatially-localized expression of proteins. Dasatinib was
      modified with trans-cyclooctene (TCO), and its cytoplasmic target kinases were
      expressed in intracellular compartments, such as endosomes and F-actins. After
      bioorthogonal labeling, the colocalization between Dasatinib and its target
      proteins was observed in intracellular compartments.

PMID- 27711356
TI  - Correction: A desferrioxamine B squaramide ester for the incorporation of
      zirconium-89 into antibodies.
AB  - Correction for 'A desferrioxamine B squaramide ester for the incorporation of
      zirconium-89 into antibodies' by Stacey E. Rudd et al., Chem. Commun., 2016, DOI:
      .

PMID- 27711357
TI  - Correction: Metal complexes as "protein surface mimetics".
AB  - Correction for 'Metal complexes as "protein surface mimetics"' by Sarah H. Hewitt
      and Andrew J. Wilson, Chem. Commun., 2016, 52, 9745-9756.

PMID- 27711359
TI  - Gold(i)-catalyzed C-glycosylation of glycosyl ortho-alkynylbenzoates: the role of
      the moisture sequestered by molecular sieves.
AB  - C-Glycosylation of glycosyl ortho-hexynylbenzoates with allyltrimethylsilane or
      silyl enol ethers could proceed smoothly under the catalysis of Ph3PAuNTf2 to
      provide the corresponding C-glycosides in high yields and stereoselectivity,
      wherein the moisture sequestered by the molecular sieves was disclosed to play a
      critical role in the gold(i)-catalytic cycle.

PMID- 27711358
TI  - A dual-functional supramolecular hydrogel based on a spiropyran-galactose
      conjugate for target-mediated and light-controlled delivery of microRNA into
      cells.
AB  - A supramolecular hydrogel formed by spiropyran conjugated galactose was developed
      for light-controlled release of miR-122 and target-mediated delivery of the miRNA
      into HepG2 cells cultured on top of the gel.

PMID- 27711360
TI  - Correction: CuFeS2 colloidal nanocrystals as an efficient electrocatalyst for dye
      sensitized solar cells.
AB  - Correction for 'CuFeS2 colloidal nanocrystals as an efficient electrocatalyst for
      dye sensitized solar cells' by Yihui Wu et al., Chem. Commun., 2016, DOI: .

PMID- 27711361
TI  - A heteropentanuclear metal string complex [Mo2NiMo2(tpda)4(NCS)2] with two
      linearly aligned quadruply bonded Mo2 units connected by a Ni ion and a meso
      configuration of the complex.
AB  - A dimeric molybdenum precursor and nickel ions are used to synthesize a symmetric
      heteropentanuclear complex, [Mo2NiMo2(tpda)4(NCS)2]. This complex possesses
      unique structural features, as the four ligands are coordinated to the metal
      framework in a meso configuration. Furthermore, the central Ni2+ ion is in a high
      spin state.

PMID- 27711362
TI  - Tetraphenylethene (TPE) modified polyhedral oligomeric silsesquioxanes (POSS):
      unadulterated monomer emission, aggregation-induced emission and nanostructural
      self-assembly modulated by the flexible spacer between POSS and TPE.
AB  - Mono-TPE modified POSS molecules, in which the flexible spacers between TPE and
      POSS moieties control their self-assembly and aggregation, exhibit a unique
      unadulterated monomer emission in organic solvents as well as an AIE emission in
      THF/water.

PMID- 27711363
TI  - Correction: Selective precipitation of alkyl dihalides using a newly synthesized
      water-soluble bisphosphorylpillar[5]arene.
AB  - Correction for 'Selective precipitation of alkyl dihalides using a newly
      synthesized water-soluble bisphosphorylpillar[5]arene' by Wenjin Cheng et al.,
      Chem. Commun., 2016, 52, 8075-8078.

PMID- 27711364
TI  - Catalytic dehydrocoupling of amines and boranes by an incipient tin(ii) hydride.
AB  - The facile heterodehydrocoupling of a range of primary or secondary amines and
      even ammonia with pinacolborane (HBPin) was accomplished using {ArMe6Sn(MU-OMe)}2
      (1, ArMe6 = C6H3-2,6-(C6H2-2,4,6-Me3)2) as pre-catalysts for a catalytically
      active tin(ii) hydride. The more sterically hindered pre-catalyst 2, {AriPr4Sn(MU
      OMe)}2 (AriPr4 = C6H3-2,6-(C6H3-2,6-iPr2)2) facilitated the dehydrocoupling only
      of primary amines with HBPin, and at an increased rate relative to the less
      crowded {ArMe6Sn(MU-OMe)}2. Also presented is {ArMe6Sn(MU-NEt2)}2 (3), which can
      be converted into the structurally characterizable {ArMe6Sn(MU-NEt2)(MU
      H)SnArMe6} (4) via the addition of pinacol borane. This, alongside stoichiometric
      studies, give insight into the mechanism of the catalysis.

PMID- 27711365
TI  - The potential of a graphene-supported porous-organic polymer (POP) for CO2
      electrocatalytic reduction.
AB  - A one-pot, bottom-up assembly of a pyrimidine-containing porous-organic polymer
      (PyPOP) was conducted to homogenously deposit the PyPOP atop unmodified graphene
      sheets, affording a composite material PyPOP@G. The PyPOP demonstrated an
      appreciable affinity toward CO2 capture but was found to be largely insulating,
      hindering its usage in potential electrochemical conversion of CO2. However, its
      composite with graphene was found to be microporous, with maintained affinity
      toward CO2 and furthermore demonstrated significant electrochemical activity
      toward CO2 reduction (5 mA cm-2 at -1.6 V), not observed in either of its two
      components separately.

PMID- 27711366
TI  - Bimetal-organic-frameworks-derived yolk-shell-structured porous Co2P/ZnO@PC/CNTs
      hybrids for highly sensitive non-enzymatic detection of superoxide anion released
      from living cells.
AB  - We report a general approach for the synthesis of yolk-shell-structured porous
      dicobalt phosphide/zinc oxide@porous carbon polyhedral/carbon nanotube hybrids
      (Co2P/ZnO@PC/CNTs) derived from bimetal-organic frameworks, and explore their
      potential utilization in the electrochemical sensing of superoxide anions. Beyond
      our expectation, the trace level of O2- released from living cells has also been
      successfully captured by our designed sensor. The presented strategy for the
      controlled design and synthesis of bimetal-organic frameworks-derived functional
      nanomaterials offers prospects of developing highly active electrocatalysts in
      non-enzyme sensors.

PMID- 27711367
TI  - Correction: Fluorogenic bidirectional displacement probe-based real-time
      isothermal DNA amplification and specific visual detection of products.
AB  - Correction for 'Fluorogenic bidirectional displacement probe-based real-time
      isothermal DNA amplification and specific visual detection of products' by Xiong
      Ding et al., Chem. Commun., 2016, 52, 11438-11441.

PMID- 27711368
TI  - Correction: Highly efficient photoelectrochemical water splitting by a hybrid
      tandem perovskite solar cell.
AB  - Correction for 'Highly efficient photoelectrochemical water splitting by a hybrid
      tandem perovskite solar cell' by Abd. Rashid Bin et al., Chem. Commun., 2016, 52,
      5824-5827.

PMID- 27711369
TI  - The growth and thermal properties of Au deposited on Rh(111): formation of an
      ordered surface alloy.
AB  - Scanning tunnelling microscopy (STM), low energy ion scattering spectroscopy
      (LEIS), X-ray photoelectron spectroscopy (XPS) and high resolution electron
      energy loss spectroscopy (HREELS) were applied for studying Au deposited on the
      Rh(111) surface. Both the deposition of Au at different substrate temperatures
      (400-800 K) and the effect of annealing Au deposited at 500 K were investigated.
      Gold deposition at 500 K, investigated by STM and LEIS methods, revealed that up
      to half monolayer Au the system exhibits clearly layer-by layer growth; however,
      above this coverage a slight deviation was identified, mainly due to kinetic and
      morphological effects. A continuous cover layer of Au was formed only above ~2.5
      monolayers (ML). Below this coverage, the pseudomorphic character of the Au
      overlayer was clearly proven by STM, but this feature disappears at 4 ML
      coverage. A moderate (5-10%) surface mixing of the two metals was observed only
      above 600 K, for both annealing the Au layer formed at lower temperatures and
      performing the deposition at elevated temperatures. Above 600 K a clear step-flow
      growth mechanism was verified. Depending on the Au coverage, a more extended
      mixing of the top layer and the sublayer was observed at even higher
      temperatures. In this case, nano-range ordering of the alloyed layer was detected
      by STM, where the lateral extension of the uniform commensurate (2 * 1) domains
      was around 4 * 4 nm2. In this case, the local intralayer mixing of Rh and Au can
      locally reach a value of 50%. The proposed structural model for the (2 * 1) alloy
      phase was also corroborated by HREELS investigations on CO adsorption.

PMID- 27711370
TI  - Shape-controlled synthesis of CO-free Pd nanocrystals with the use of formic acid
      as a reducing agent.
AB  - This paper reports the use of formic acid as a reducing agent for the shape
      controlled synthesis of Pd nanocrystals with no chemisorption of CO on the
      surface, as confirmed by attenuated total reflection Fourier transform infrared
      (ATR-FT-IR) spectroscopy.

PMID- 27711371
TI  - Sulfur ion concentration dependent morphological evolution of CdS thin films and
      its subsequent effect on photo-electrochemical performance.
AB  - The sulfur ion concentration dependent morphological evolution and its subsequent
      effect on photo-electrochemical properties of chemically synthesized CdS thin
      films have been systematically investigated. The plausible growth mechanism for
      the morphological evolution of CdS thin films due to a change in sulfur ion
      concentration has been proposed. Scanning electron micrographs (SEMs) reveal that
      the morphology of CdS thin films has been changed from spherical grains to
      vertically aligned nanoflakes by systematic control of sulfur ion concentration.
      This article elucidates the astute relationships between precursor
      concentrations, reaction rate and morphological evolution. The X-ray diffraction
      (XRD) patterns reveal the formation of hexagonal wurtzite CdS thin films with the
      preferred (002) orientation for CdS nanoflakes, which is further supported by the
      analysis of the high resolution transmission electron micrographs (HRTEMs).
      Optical absorption studies show a red shift in the absorption edge with an
      increase in sulfur concentration. The beneficial role of nanoflake formation is
      easily reflected in the photo-electrochemical performance. Improved solar cell
      performances are observed for CdS nanoflakes grown with a sulfur to cadmium ion
      concentration ratio of 4 (S : Cd = 4).

PMID- 27711372
TI  - Relative extent of double and single Auger decay in molecules containing C, N and
      O atoms.
AB  - We show that the proportion of double Auger decay following creation of single 1s
      core holes in molecules containing C, N and O atoms is greater than usually
      assumed, amounting to about 10% of single Auger decay in many cases. It varies
      from molecule to molecule, where the size of the molecule has a positive
      correlation to the amount of double Auger decay. In neon, examined as a related
      benchmark, the proportion of double Auger decay is similar to that in methane,
      and is in the order of 5%.

PMID- 27711373
TI  - Mechanisms of peptide hydrolysis by aspartyl and metalloproteases.
AB  - Peptide hydrolysis has been involved in a wide range of biological,
      biotechnological, and industrial applications. In this perspective, the
      mechanisms of three distinct peptide bond cleaving enzymes, beta secretase
      (BACE1), insulin degrading enzyme (IDE), and bovine lens leucine aminopeptidase
      (BILAP), have been discussed. BACE1 is a catalytic Asp dyad [Asp, Asp-]
      containing aspartyl protease, while IDE and BILAP are mononuclear [Zn(His, His,
      Glu)] and binuclear [Zn1(Asp, Glu, Asp)-Zn2(Lys, Glu, Asp, Asp)] core possessing
      metallopeptidases, respectively. Specifically, enzyme-substrate interactions and
      the roles of metal ion(s), the ligand environment, second coordination shell
      residues, and the protein environment in the functioning of these enzymes have
      been elucidated. This information will be useful to design small inhibitors,
      activators, and synthetic analogues of these enzymes for biomedical,
      biotechnological, and industrial applications.

PMID- 27711374
TI  - Metal ion-modulated self-assembly of pseudo-suit[3]anes using crown ether-based
      terpyridine metalloprisms.
AB  - Two hexanuclear metalloprisms possessing three dibenzo[24]crown-8 units were
      generated in quantitative yields by complexation of the predesigned tetratopic
      2,2':6',2''-terpyridine ligand (T) with CdII and ZnII ions, respectively. The
      prismatic hosts were subsequently self-assembled with the trifunctional guest
      molecule (TriG) containing dibenzylammonium ions to afford the corresponding
      metallo-supramolecular pseudo-suit[3]anes. It was serendipitously found that the
      host-guest inclusion rates could be modulated by the subtle dynamic difference in
      metal-ligand frameworks, finally leading to a selective encapsulation event in
      the presence of both metallo-suits.

PMID- 27711375
TI  - Construction of a pillar[6]arene based water-soluble supramolecular
      pseudopolyrotaxane driven by cucurbit[8]uril-enhanced pi-pi interaction.
AB  - A new pillar[6]arene based water-soluble supramolecular pseudopolyrotaxane whose
      repeating units are connected through cucurbit[8]uril-enhanced pi-pi interaction
      is successfully fabricated.

PMID- 27711376
TI  - pH-Sensitive fluorophores from locked GFP chromophores by a non-alternant
      analogue of the photochemical meta effect.
AB  - We report the synthesis and characterization of a pH-sensitive fluorescence
      switch based on a conformationally-locked green fluorescent protein (GFP)
      chromophore. The chromophore differs from difluoroboryl-locked parent by the
      addition of a titratable alcohol group on the imidazolinone ring. The chromophore
      is fluorescent at pH <= 5, but becomes non-fluorescent at higher pH, where the
      substituent is ionized. We use a quantum chemical model to show that the
      mechanism of the fluorescence turn-off is electronically analogous to
      photochemical meta effects in aryl-containing systems.

PMID- 27711377
TI  - Encapsulation capacity and natural payload delivery of an anticancer drug from
      boron nitride nanotube.
AB  - The behavior of confined anticancer carboplatin (CPT) molecules in a single (10,
      10) boron nitride nanotube (BNNT) was studied by means of molecular dynamics
      simulations. Our study revealed a very large storage capacity of BNNT. Analysis
      of the energy profiles depending on the number of confined molecules, and on
      their spatial organization allowed us to quantify the ability of BNNT to
      vectorize CPT. Indeed, BNNT despite its small radius presented a large inner
      volume that favored stable encapsulation of multiple active anticancer molecules.
      Moreover, in our molecular dynamics simulations, the empty BNNT and the BNNT
      filled with CPT diffused spontaneously to the cell membrane and were able to
      passively enter inside lipid bilayers by a lipid-assisted mechanism. This
      property has been used to deliver naturally anticancer drugs to cellular targets.
      Using this enhanced drug delivery system, we have provided a definitive solution
      to the problem of drug release and have thus opened up a new way of targeting
      cancer cells. Indeed, regardless of the mode of action of the platinum complex
      towards the cell, the delivery of the drug on site should limit the side effects
      of the drug.

PMID- 27711378
TI  - A desferrioxamine B squaramide ester for the incorporation of zirconium-89 into
      antibodies.
AB  - A squaramide ester derivative of desferrioxamine B (H3DFO) that is compatible
      with aqueous solvents and does not induce antibody aggregation is used to attach
      the siderophore to the antibody trastuzumab. The new conjugates were radiolabeled
      with zirconium-89 to give complexes that are more resistant to ligand exchange
      when compared to currently used H3DFO derivatives and result in high quality
      positron emission tomography images in mouse models of HER2 positive breast
      cancer.

PMID- 27711379
TI  - Improving the photocatalytic activity of s-triazine based graphitic carbon
      nitride through metal decoration: an ab initio investigation.
AB  - Graphitic carbon nitride based semiconductor materials are found to be potential
      photocatalysts for generating hydrogen through solar water splitting. Through
      more accurate hybrid density functional theory calculations, we attempted to tune
      the electronic band structure of poly s-triazine based graphitic carbon nitride
      by decorating it with different metal atoms and clusters for improving its
      visible light absorption efficiency. For deposition on the two-dimensional carbon
      nitride surface, a range of metals have been considered which include all the 3d
      transition metals and the noble metals (Ag, Au, Pt and Pd). Our study reveals
      that though the band gaps of all the metal decorated systems were less than that
      of pristine carbon nitride, in most of the cases, metal decoration leads to the
      formation of mid gap impurity states, which can hinder the mobility of charge
      carriers. However, in the case of Ag and its four atom cluster deposited systems,
      no mid gap states were observed. In all the metal decorated systems, the measured
      band edge potentials were also found to satisfy the thermodynamic criterion for
      overall water splitting. The calculated optical absorption spectra show a shift
      in the absorption band towards the visible region upon metal decoration. Our
      results indicate that among all the considered metal atoms silver is the
      preferred candidate for deposition on the carbon nitride surface for improved
      photocatalytic activity.

PMID- 27711380
TI  - Genetically encoded fluorophenylalanines enable insights into the recognition of
      lysine trimethylation by an epigenetic reader.
AB  - Fluorophenylalanines bearing 2-5 fluorine atoms at the phenyl ring have been
      genetically encoded by amber codon. Replacement of F59, a phenylalanine residue
      that is directly involved in interactions with trimethylated K9 of histone H3, in
      the Mpp8 chromodomain recombinantly with fluorophenylalanines significantly
      impairs the binding to a K9-trimethylated H3 peptide.

PMID- 27711382
TI  - A localized surface plasmon resonance-enhanced photoelectrochemical biosensing
      strategy for highly sensitive and scatheless cell assay under red light
      excitation.
AB  - In this work, a novel photoelectrochemical biosensing strategy was designed for
      cell assay under 630 nm (red light) excitation. WS2/Au NP nanocomposites were
      prepared as a photoelectrochemical biosensing substrate. The localized surface
      plasmon resonance effect of Au NPs tremendously improved the photoelectric
      conversion efficiency and enhanced the detection sensitivity.

PMID- 27711381
TI  - Dual-mode crystal-bound and X-type passivation of quantum dots.
AB  - In this report, we present a new path to the control of quantum dot surface
      chemistry that can lead to a better understanding of nanoscale interfaces and the
      development of improved photocatalysts. Control of the synthetic methodology
      leads to QDs that are concomitantly ligated by crystal-bound organics at the
      surface anion sites and small X-type ligands on the surface cation sites.

PMID- 27711383
TI  - Probing ligand-induced modulation of metallic states in small gold nanoparticles
      using conduction electron spin resonance.
AB  - Thiolate-protected gold nanoparticles have a rich history as model systems for
      understanding the physical and chemical properties of metallic nanoscale
      materials that, in turn, form the basis for applications in areas such as
      molecular electronics, photocatalytic systems, and plasmonic solar cells. It is
      well known that the electronic properties of gold nanoparticles can be tuned by
      modifying the geometry, size and dielectric surrounding of the particle. However,
      much less is known of how modifications to the surface chemistry modulates the
      electronic properties of gold nanoparticles. In part, this stems from the fact
      that there are few good tools for measuring the electronic properties with the
      sensitivity required for following the response to subtle changes in surface
      chemistry. In this work, we demonstrate conduction spin electron resonance (CESR)
      to be a sensitive and selective probe to determine how changes in surface
      chemistry of gold nanoparticles affect the metallic states near the Fermi energy.
      Using a series of para-substituted aromatic thiolate ligands, we find that the g
      factor, as measured using CESR, correlates well with experimental and
      computational parameters often used to understand ligand effects in classical
      inorganic complexes. This suggests classical inorganic reasoning can function as
      a framework for understanding how to control the electronic properties of gold
      nanoparticles using their surface chemistry.

PMID- 27711384
TI  - Selective shrinkage and separation of isomeric naphthoic acids via supramolecular
      gelation.
AB  - The isomeric non-gelator molecules 1- or 2-naphthoic acid (NA1, or NA2) were
      found to form two-component supramolecular gels with an amphiphilic gelator
      LHC18, and the NA2/LHC18 gel underwent shrinking at room temperature. Using such
      properties, NA1 and NA2 were separated via gel shrinkage.

PMID- 27711385
TI  - Theoretical prediction of long-range ferromagnetism in transition-metal atom
      doped d0 dichalcogenide single layers SnS2 and ZrS2.
AB  - We have systematically investigated the effects of transition-metal (TM) atom (Sc
      Zn) doping in 2D d0 materials SnS2 and ZrS2via the density functional theory
      method. Our results demonstrate that the conductivity and magnetism of SnS2 and
      ZrS2 can be engineered to spin-polarize half-metal/metal with appropriate TM
      dopants. For both materials, nontrivial magnetic interactions can be induced by
      V/Cr/Mn/Fe/Co doping. Specifically, the various behaviors of the magnetic
      exchanges in TM-doped SnS2 and ZrS2 are due to the competition between the super
      exchange, the double exchange, and the p-d exchange interactions, which are
      dependent on the dopants' chemistry and spatial positions. Thus, our results give
      potential guidance for future experiments to create functionalized d0 nano
      electronic devices.

PMID- 27711386
TI  - Modelling the local atomic structure of molybdenum in nuclear waste glasses with
      ab initio molecular dynamics simulations.
AB  - The nature of chemical bonding of molybdenum in high level nuclear waste glasses
      has been elucidated by ab initio molecular dynamics simulations. Two
      compositions, (SiO2)57.5-(B2O3)10-(Na2O)15-(CaO)15-(MoO3)2.5 and (SiO2)57.3
      (B2O3)20-(Na2O)6.8-(Li2O)13.4-(MoO3)2.5, were considered in order to investigate
      the effect of ionic and covalent components on the glass structure and the
      formation of the crystallisation precursors (Na2MoO4 and CaMoO4). The
      coordination environments of Mo cations and the corresponding bond lengths
      calculated from our model are in excellent agreement with experimental
      observations. The analysis of the first coordination shell reveals two different
      types of molybdenum host matrix bonds in the lithium sodium borosilicate glass.
      Based on the structural data and the bond valence model, we demonstrate that the
      Mo cation can be found in a redox state and the molybdate tetrahedron can be
      connected with the borosilicate network in a way that inhibits the formation of
      crystalline molybdates. These results significantly extend our understanding of
      bonding in Mo-containing nuclear waste glasses and demonstrate that tailoring the
      glass composition to specific heavy metal constituents can facilitate
      incorporation of heavy metals at high concentrations.

PMID- 27711392
TI  - Strong Fermi level pinning induces a high rectification ratio and negative
      differential resistance in hydrogen bonding bridged single cytidine pair
      junctions.
AB  - We propose a high performance single molecule rectifier by sandwiching a
      deoxycytidine base pair between gold electrodes. The conductance of the single
      base pair junction can be controlled by its protonation status, with ON/OFF
      ratios between the protonated (pCC) and deprotonated (CC) junctions of 3-5 orders
      of magnitude. In the conducting pCC state, we observed a high rectification ratio
      of two orders of magnitude at bias voltage values around 0.1 V. This
      rectification ratio surpasses most of the theoretical designs for single
      molecular rectifiers, while the low working voltage implies significant energy
      efficiency. Negative differential resistance (NDR) was also witnessed in the
      protonated state, with a peak to valley ratio of 24. Both the rectifying and NDR
      effects originate from strong Fermi level pinning effects. The electronic
      performance offers these single base pair junctions potential applications as a
      unimolecular rectifier or switch with an NDR effect. The current-voltage response
      is unique compared with those of the reported canonical A-T and G-C pairs, and
      provides the possibility to be used for i-motif DNA structure recognition or
      sequencing.

PMID- 27711393
TI  - Solvent effects on the thermal isomerization of a rotary molecular motor.
AB  - As molecular machines move to exciting applications in various environments, the
      study of medium effects becomes increasingly relevant. It is difficult to predict
      how, for example, the large apolar structure of a light-driven rotary molecular
      motor is affected by a biological setting or surface proximity, while for future
      nanotechnology precise fine tuning and full understanding of the isomerization
      process are of the utmost importance. Previous investigations into solvent
      effects have mainly focused on the relatively large solvent-solute interaction of
      hydrogen bonding or polarization induced by the isomerization process. We present
      a detailed study of a key step in the rotary process i.e. the thermal helix
      inversion of a completely apolar rotary molecular motor in 50 different solvents
      and solvent mixtures. Due to the relative inertness of this probe, we are able to
      study the influence of subtle solvent-solvent interactions upon the rate of
      rotation. Statistical analysis reveals which solvent parameters govern the
      isomerization process.

PMID- 27711394
TI  - Formal total synthesis of (+/-)-strictamine - the [2,3]-Stevens rearrangement for
      construction of octahydro-2H-2,8-methanoquinolizines.
AB  - For decades, akuammiline alkaloids have attracted synthetic chemists due to their
      intriguing molecular architecture. Among the different structural elements
      embedded in their carboskeleton, the methanoquinolizidine system constitutes the
      signature structural element of this alkaloid family. Herein, we describe a novel
      synthetic access to this system which relies on a [2,3]-Stevens rearrangement and
      results in the formal synthesis of strictamine.

PMID- 27711395
TI  - A non-dissociative open-flask hydroboration with ammonia borane: ready synthesis
      of ammonia-trialkylboranes and aminodialkylboranes.
AB  - Under open-flask conditions, ammonia borane hydroborates olefins in refluxing
      tetrahydrofuran. Unlike conventional hydroboration, the Lewis base (ammonia) is
      not dissociated from the boron center. Terminal alkenes selectively provide
      ammonia-trialkylborane complexes. On the other hand, internal alkenes afford
      aminodialkylboranes via a metal-free hydroboration-dehydrogenation sequence.
      Alkaline hydrogen peroxide oxidation of the products provides the corresponding
      alcohols in high yields.

PMID- 27711396
TI  - Elastic coupling between spin-crossover particles and cellulose fibers.
AB  - Composite materials made of cellulose fibers and spin crossover micro-particles
      were investigated by magnetic measurements and dynamic mechanical analysis (DMA).
      The storage modulus of the cellulose handsheet (0.6 GPa at room T) is
      significantly enhanced in the composite (1.7 GPa). The latter also displays a
      reversible increase of ca. 10% when switching the magnetic spin state of the
      particles from the low spin (LS) to the high spin (HS) form. Around the spin
      transition temperature a loss modulus peak is also observed, highlighting the
      strong viscoelastic coupling between the particles and the cellulose matrix.
      These results pave the way for the development of a novel family of actuator
      materials based on spin crossover-polymer composites.

PMID- 27711397
TI  - Transition-sized Au92 nanoparticle bridging non-fcc-structured gold nanoclusters
      and fcc-structured gold nanocrystals.
AB  - Herein, we report the intriguing structure, optical absorption and
      electrochemical properties of the transition-sized Au92(TBBT)44 (Au92 for short,
      TBBT = 4-tert-butylbenzenethiolate) nanoparticle. An interesting observation is
      the 4H phase array of Au92 nanoparticles in the unit cells of single crystals.

PMID- 27711399
TI  - New insights into the photoswitching mechanisms of normal dithienylethenes.
AB  - The photoswitching and competitive processes of the referent photochromic
      diarylethene derivative 1,2-bis(2,4-dimethyl-5-phenyl-3
      thienyl)perfluorocyclopentene (DTE) and a novel bridged analog DTE-m5 have been
      investigated by state-of-the-art TD-DFT calculations and ultrafast spectroscopy
      supported by advanced chemometric data treatments. Focusing on DTE, the overall
      deactivation pathway of both antiparallel (AP) and parallel (P) conformers of the
      open form (OF) (1 : 1 in solution) has been resolved and rationalized starting
      from the Franck-Condon (FC) region to the ground state recovery. For the photo
      excited P conformer, after ultrafast relaxation (~200 fs) towards the S1 relaxed
      state, an expected ISC occurred (55 ps) to produce a triplet state, 3P, the
      latter relaxing within 2.5 MUs. Concerning the AP conformer, the photocyclization
      reaction is reported to proceed immediately (100 fs) starting from the FC region
      while the relaxed singlet state is populated in parallel. For the first time, we
      discovered that the latter state evolves through an unexpected ISC process (1 ps)
      giving rise to a second triplet state,3AP. For DTE-m5, by slightly constraining
      the molecule with the bridge, this triplet becomes reactive and participates in
      the formation of 10% of closed form (CF) probably through an adiabatic mechanism.
      Concerning the photoreversion, in accordance with the literature, we report on a
      two-step process, a 190 fs vibrational relaxation followed by a 6 ps ring-opening
      reaction. For the overall species at the singlet or triplet manifold, the use of
      advanced MCR-ALS allows us to obtain specific spectral signatures. This study is
      therefore a new step within the comprehension of DTE photochemistry.

PMID- 27711398
TI  - Long-lived states to sustain SABRE hyperpolarised magnetisation.
AB  - The applicability of the magnetic resonance (MR) technique in the liquid phase is
      limited by poor sensitivity and short nuclear spin coherence times which are
      insufficient for many potential applications. Here we illustrate how it is
      possible to address both of these issues simultaneously by harnessing long-lived
      hyperpolarised spin states that are formed by adapting the Signal Amplification
      by Reversible Exchange (SABRE) technique. We achieve more than 4% net 1H
      polarisation in a long-lived form that remains detectable for over ninety seconds
      by reference to proton pairs in the biologically important molecule nicotinamide
      and a pyrazine derivative whose in vivo imaging will offer a new route to probe
      disease in the future.

PMID- 27711400
TI  - Understanding of the formation of shallow level defects from the intrinsic
      defects of lead tri-halide perovskites.
AB  - Organic-inorganic hybrid perovskites have unique electronic properties in which
      deep level defects are rarely formed. This unique defect characteristic is the
      source of the long carrier diffusion length. This theoretical study shows what
      causes this characteristic formation of shallow level defects in lead tri-halide
      perovskites. Comparative studies between iodides and other halides showed that
      deep level defect states were generated for Cl based perovskites. Longer Pb
      halide bond lengths and narrower band gaps are beneficial for preventing deep
      level defect states. Additionally, our study shows that the formation of shallow
      level defects does not change even when the lattice structures of the perovskites
      do not reach their equilibrium structures.

PMID- 27711402
TI  - Photodissociation dynamics of dinitrite at 355 nm: initiation of a reactive
      pathway.
AB  - Dinitrites are effective nitrosating reagents in preparative chemistry and their
      decomposition products are involved in the atmospheric reaction of volatile
      organic compounds with nitrogen oxides (NOx). In this work, photodissociation
      dynamics of five alkyl dinitrites were investigated by detecting the LIF spectra
      of the dissociation products and theoretical calculations. The results showed
      that the C-C bond connecting the two nitrosooxy (-ONO) functional groups was the
      weakest bond in vicinal dinitrites and aldehydes were the dissociation products.
      For dinitrites with two ONO groups separated by a CH2 group, vinoxy and 1
      methylvinoxy radicals were detected as the fragments via photodissociation,
      indicating a different mechanism compared to thermal decomposition. This
      observation demonstrated that a new reactive pathway could be initiated by
      photolysis of dinitrites.

PMID- 27711401
TI  - Tandem neopentyl glycol maltosides (TNMs) for membrane protein stabilisation.
AB  - A novel class of detergents, designated tandem neopentyl glycol maltosides
      (TNMs), were evaluated with four target membrane proteins. The best detergent
      varied depending on the target, but TNM-C12L and TNM-C11S were notable for their
      ability to confer increased membrane protein stability compared to DDM. These
      agents have potential for use in membrane protein research.

PMID- 27711403
TI  - Removal of alkali and transition metal ions from water with hydrophobic deep
      eutectic solvents.
AB  - Hydrophobic deep eutectic solvents were used for the first time for the removal
      of metal ions from non-buffered water. It was shown that the extraction occurs
      via an ion exchange mechanism in which all transition metal ions could be
      extracted with high distribution coefficients, even for high Co2+ concentrations
      and low DES/water mass ratios. Maximum extraction efficiency could be reached
      within 5 s and regeneration was possible.

PMID- 27711404
TI  - Benzoannelated aza-, oxa- and azaoxa[8]circulenes as promising blue organic
      emitters.
AB  - In the present work, we studied the synergetic effect of benzoannelation and NH/O
      substitution for enhancing the absorption intensity in a series of novel designed
      benzoannelated aza- and oxa[8]circulenes. Semi-empirical estimations of the
      fluorescence rate constants allowed us to determine the most promising
      fluorophores among all the possible benzoannelated aza-, oxa- and mixed
      azaoza[8]circulenes. Among them, para-dibenzoannelated [8]circulenes demonstrated
      the most intense light absorption and emission due to the prevailing role of the
      linear acene chromophore. Calculated phifl values are in complete agreement with
      experimental data for a number of already synthesized circulenes. Thus, we
      believe that the most promising circulenes designed in this study can demonstrate
      an intensive fluorescence in the case of their successful synthesis, which in
      turn could be extremely useful for the fabrication of future blue OLEDs. Special
      attention is devoted to the aromaticity features and peculiarities of the
      absorption spectra for the two highly-symmetrical (D4h ground state symmetry) pi
      isoelectronic species as well as the so-called tetrabenzotetraaza[8]circulene and
      tetrabenzotetraoxa[8]circulene molecules. Both of them are characterized by rich
      electronic spectra, which can be assigned only by taking into account the
      vibronic coarse structure of the first electronic absorption band; the 0-1 and 0
      2 transitions were found to be active in the absorption spectrum in complete
      agreement with experimental data obtained for both energy and intensity. The
      corresponding promotive vibrational modes have been determined and their vibronic
      activity estimated using the Franck-Condon approximation.

PMID- 27711405
TI  - Influence of electric potential on the apparent viscosity of an ionic liquid:
      facts and artifacts.
AB  - According to recent findings, the steady shear viscosity of the ionic liquid 1
      ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Emim][Tf2N])
      decreases significantly under the influence of electric potential. This implies a
      causal connection between nanoscale ordering at the electrified interface and a
      macroscopic change of transport properties. To study this phenomenon in more
      detail, we reproduced the above-mentioned measurements; however, we find no
      evidence that the viscosity of [Emim][Tf2N] is a function of electric potential.
      Additionally, our results show that steady shear measurements can lead to
      artifacts that, at first glance, may appear to be potential-induced changes in
      viscosity. We demonstrate that the artifacts result from a sliding electrical
      contact at the working electrode of the electrochemical cell and we suggest to
      consider our findings for future viscosity measurements of ionic liquids.

PMID- 27711406
TI  - The flow patterning capability of localized natural convection.
AB  - Controlling flow patterns to align materials can have various applications in
      optics, electronics, and biosciences. In this study, we developed a natural
      convection-based method to create desirable spatial flow patterns by controlling
      the locations of heat sources. Fluid motion in natural convection is induced by
      the spatial fluid density gradient that is caused by the established spatial
      temperature gradient. To analyze the patterning resolution capability of this
      method, we used a mathematical model combined with nondimensionalization to
      correlate the flow patterning resolution with experimental operating conditions.
      The nondimensionalized model suggests that the flow pattern and resolution is
      only influenced by two dimensionless parameters, and , where Gr is the Grashof
      number, representing the ratio of buoyancy to the viscous force acting on a
      fluid, and Pr is the Prandtl number, representing the ratio of momentum
      diffusivity to thermal diffusivity. We used the model to examine all of the flow
      behaviors in a wide range of the two dimensionless parameter group and proposed a
      flow pattern state diagram which suggests a suitable range of operating
      conditions for flow patterning. In addition, we developed a heating wire with an
      angular configuration, which enabled us to efficiently examine the pattern
      resolution capability numerically and experimentally. Consistent resolutions were
      obtained between the experimental results and model predictions, suggesting that
      the state diagram and the identified operating range can be used for further
      application.

PMID- 27711407
TI  - Initial dissolution of D2O at the gas-liquid interface of the ionic liquid
      [C4min][NTf2] associated with hydrogen-bond network formation.
AB  - We have studied the initial dissolution of D2O at the interfacial surface of the
      flowing jet sheet beam of the ionic liquid (IL) [C4min][NTf2] using the King and
      Wells method as a function of both the temperature and collision energy of the
      IL. The initial dissolution probability of D2O into the IL [C4min][NTf2] was
      found to follow the general propensity that the solubility of gases into a liquid
      decreases with temperature. However, a large partial molar enthalpy and entropy
      for the initial dissolution of D2O in the IL [C4min][NTf2] were observed from the
      temperature dependence of the initial dissolution probability: DeltaHl = -53 +/-
      8 kJ mol-1, DeltaSl = -210 +/- 30 J mol-1 K-1. In addition, it was found that the
      collision energy significantly reduced the initial dissolution probability. We
      propose that the associated D2O molecules at the interface of the IL
      [C4min][NTf2] make a hydrogen-bond network around the [NTf2]- anion before
      dissolution into the deeper portion of the interface layer.

PMID- 27711408
TI  - Complexes of Ni(ii) and Cu(ii) with small peptides: deciding whether to
      deprotonate.
AB  - The observed variety of metal-ion complexation sites offered by peptides reflects
      a basic tension between charge solvation of the ion by Lewis-basic chelating
      groups versus amide nitrogen deprotonation and formation of metal-nitrogen bonds.
      Gas-phase models of metal-ion coordination can illuminate the factors governing
      this choice in condensed-phase proteins and enzymes. Here, structures of gas
      phase complexes of Ni(ii) and Cu(ii) with tri- and tetra-peptide ligands are
      mapped out using a combination of Infrared Multiple Photon Dissociation (IRMPD)
      spectroscopy and density functional theory (DFT) computations. The two binding
      modes give distinctive IRMPD signatures, particularly in the diagnostic region
      1500-1550 cm-1. Previous observations have suggested that Ni(ii) complexes
      preferentially show the iminol rearrangement pattern (Im) giving low-spin square
      planar geometries with metal-ion bonds to deprotonated amide nitrogens. In
      contrast, alkaline earth metal ion complexes prefer amide carbonyl oxygens
      chelating the metal ion with pyramidal geometry (charge-solvation, CS).
      Surprisingly, it is shown here that the Gly4 complexes are CS bound, in contrast
      with the expectation of Im binding. It is suggested that CS binding is actually a
      normal Ni(ii) and Cu(ii) binding mode to simple peptides lacking participating
      side chains. Three factors are suggested to influence the choice between CS and
      Im binding patterns: (1) presence of an accessible side-chain Lewis-basic proton
      interaction site (FGGF, FGG and HAA complexes); (2) short chain length of the
      peptide leading to a shortage of accessible carbonyl oxygen sites for CS binding,
      (AAA, FGG and HAA complexes); (3) outright deprotonation of the ligand giving net
      negatively charged Im[Ni2+(Gly4-3H+)]- and Im[Ni2+(Ala3-3H+)]- complexes, which
      have a triply-deprotonated ligand. IRMPD spectra of [Cu2+Gly4]2+ and [Cu2+(Gly4
      3H+)]- complexes suggest that their structures are similar to their Ni2+ analogs.

PMID- 27711409
TI  - First-principles assessment of CO2 capture mechanisms in aqueous piperazine
      solution.
AB  - Piperazine (PZ) and its blends have emerged as attractive solvents for CO2
      capture, but the underlying reaction mechanisms still remain uncertain. Our study
      particularly focuses on assessing the relative roles of PZCOO- and PZH+ produced
      from the PZ + CO2 reaction. PZCOO- is found to directly react with CO2 forming
      COO-PZCOO-, whereas PZH+ will not. However, COO-PZCOO- appears very unlikely to
      be produced in thermodynamic equilibrium with monocarbamates, suggesting that its
      existence would predominantly originate from the surface reaction that likely
      occurs. We also find production of H+PZCOO- to be more probable with increasing
      CO2 loading, due partly to the thermodynamic favorability of the PZH+ + PZCOO- ->
      H+PZCOO- + PZ reaction; the facile PZ liberation may contribute to its relatively
      high CO2 absorption rate. This study highlights an accurate description of
      surface reaction and the solvent composition effect is critical in thermodynamic
      and kinetic models for predicting the CO2 capture processes.

PMID- 27711410
TI  - C96H30 tailored single-layer and single-crystalline graphene quantum dots.
AB  - By controllable synthesis of a carbon precursor and with a suitable preparation
      routine, a series of single-layer and single-crystalline graphene quantum dots
      (GQDs) with uniform size distribution were prepared from C96H30. It was found
      that the absorption, photoluminescence (PL) and two-photon photoluminescence
      (TPPL) show a high size-dependent effect with a redshift that occurs as the size
      grows. Two-photon absorption (TPA) properties of GQDs were measured at 800 nm
      under a femtosecond pulse laser. Two-photon bioimaging of HeLa cells was carried
      out to determine TPA properties. Most significantly, the as-prepared GQDs showed
      potential in a practical application in two-photon cell bioimaging due to their
      high contrast TPPL. In addition, the superior nonlinear absorption, stable TPPL
      and excellent solubility were beneficial to the optical limiting (OL) properties.

PMID- 27711411
TI  - N2 activation on Al metal clusters: catalyzing role of BN-doped graphene support.
AB  - The successful sustenance of life demands an ambient abiotic process for N2
      activation and dissociation. The Bosch-Haber process remains the only abiotic and
      synthetic means for N2 activation and its fixation. Metal nanoclusters have been
      recently reported for activating molecular nitrogen. Interestingly, the metal
      clusters explored so far for N2 activation are free clusters and, hence, are
      practically not applicable by experimental chemists. Using density functional
      theory (DFT) based methodology, we propose a potential catalytic system for di
      nitrogen activation, viz. supported Al clusters. Al clusters supported on BN
      doped graphene sheets are seen to activate N2 molecule with a red shift in the N
      N stretching frequency up to 874 cm-1 with activation barriers as low as 1.14 eV.

PMID- 27711412
TI  - Theoretical study of the binding profile of an allosteric modulator NS-1738 with
      a chimera structure of the alpha7 nicotinic acetylcholine receptor.
AB  - Potentiation of the function of the alpha7 nicotinic acetylcholine receptor
      (alpha7-nAChR) is believed to provide a possible way for the treatment of
      cholinergic system dysfunctions such as Alzheimer's disease and schizophrenia.
      Positive allosteric modulators (PAMs) are able to augment the peak current
      response of the endogenous agonist of alpha7-nAChR by binding to some allosteric
      sites. In this study, the binding profile of a potent type I PAM, NS-1738, with a
      chimera structure (termed alpha7-AChBP) constructed from the extracellular domain
      of alpha7-nAChR and an acetylcholine binding protein was investigated with
      molecular docking, molecular dynamics simulation, and free energy calculation
      methods. We found that NS-1738 could bind to three allosteric sites of alpha7
      AChBP, namely, the top pocket, the vestibule pocket and the agonist sub-pocket.
      NS-1738 has moderate binding affinities (-6.76 to -9.15 kcal mol-1) at each
      allosteric site. The urea group is critical for binding and can form hydrogen
      bond interactions with the protein. The bulky trifluoromethyl group also has a
      great impact on the binding modes and binding affinities. We believe that our
      study provides valuable insight into the binding profiles of type I PAMs with
      alpha7-nAChR and is helpful for the development of novel PAMs.

PMID- 27711413
TI  - Solvent effects on de-excitation channels in the p-coumaric acid methyl ester
      anion, an analogue of the photoactive yellow protein (PYP) chromophore.
AB  - In an attempt to shed light on the environmental effects on the deactivation
      channels of the PYP chromophore, radiative and non-radiative deactivation
      mechanisms of the anionic p-coumaric acid methyl ester (pCE-) in the gas phase
      and water solution are compared at the CASPT2//CASSCF/cc-pVDZ level and, when
      necessary, at the CASPT2//CASPT2/cc-pVDZ level. We find that the solvent produces
      dramatic modifications on the free energy profile of the S1 state. Two twisted
      structures that are minima in the gas phase could not be localized in aqueous
      solution. Furthermore, the relative stability of minima and conical intersections
      (CIs) is reverted with respect to the gas phase values, affecting the prevalent
      de-excitation paths. As a consequence of these changes, three competitive de
      excitation channels are open in aqueous solution: the fluorescence emission from
      a planar minimum on S1, the trans-cis photoisomerization through a CI that
      involves the rotation of the vinyl double bond and the non-radiative, non
      reactive, de-excitation through the CI associated with the rotation of the single
      bond adjacent to the phenyl group. In the gas phase, the minima are the
      structures with lower energy, while in solution the CIbeta structure,
      characterized by a large charge separation, is strongly stabilized by
      interactions with water molecules and becomes the structure with the lowest
      energy on S1. These facts explain the low fluorescence signal of pCE- in aqueous
      solution and the presence of partial trans-cis photoisomerization in this system.

PMID- 27711414
TI  - Smart adsorbents with reversible photo-regulated molecular switches for selective
      adsorption and efficient regeneration.
AB  - Traditional adsorbents with fixed pore surface properties are unlikely to achieve
      both selective adsorption and efficient desorption, which are extremely desirable
      in adsorption processes. Here we report a new class of smart adsorbents by
      introducing photo-responsive azobenzene derivatives to pore interiors of
      mesoporous silica. The azobenzene molecules are applied as ON-OFF switches for
      active sites, and are reversibly regulated by UV/visible light irradiation, thus
      endowing the adsorbents with unprecedented properties to achieve selective
      adsorption and efficient desorption.

PMID- 27711415
TI  - Sorption of 3-hydroxyflavone within channel type zeolites: the effect of
      confinement on copper(ii) complexation.
AB  - The confinement effect on the complexation process of Cu(ii) by 3-hydroxyflavone
      (3HF) was investigated by studying 3HF incorporation in channel-type copper
      containing ZSM-5 and mordenite (MOR) zeolites characterized by different pore
      diameters. Complementary electronic and vibrational spectroscopy techniques point
      out two distinct behaviors upon 3HF sorption and subsequent complexation
      depending on the channel diameter in CuZSM-5 and CuMOR. To determine the
      influence of the internal environment on the interaction between the copper
      cation and the guest molecule, and to predict the structure of the complexes
      formed within the narrow-pore ZSM-5 and in the larger pore mordenite, the
      vibrational spectra of the complexes were calculated using quantum chemical
      calculations at the DFT level. From the calculations, it is derived that the
      Cu(3HF)+ chelate is formed in CuMOR indicating a weak interaction with the pore
      walls. In contrast, due to high confinement in CuZSM-5, interactions between
      copper cations and the narrower pore walls are assumed to take place in addition
      to 3HF metal complexation. To emphasize the fact that zeolites act as a solid
      solvent, 3HF complexation was also investigated in methanol solution. In such
      liquid media, a stable complex Cu(3HF)2 of 1 : 2 stoichiometry resulting in a
      double chelation with the metal cation was found to coexist with a minor species
      [Cu(3HF)(MeOH)2]+ of 1 : 1 stoichiometry. These two complexes show striking
      analogy with those observed in CuZSM-5 and CuMOR, respectively. Thus, it appears
      clearly that zeolites can constitute an ideal tool to control and orientate
      molecular reactivity for the guest in the isolated state.

PMID- 27711416
TI  - Molecular engineered nanomaterials for catalytic hydrogen evolution and
      oxidation.
AB  - The active sites of hydrogenases have inspired the design of molecular catalysts
      for hydrogen evolution and oxidation. In this feature article, we showcase key
      elements of bio-inspiration before embarking on a tour of a representative series
      of molecular hydrogen evolving catalysts (HECs) and describing the toolbox
      available for benchmarking their performances. We then show how such catalysts
      can be immobilized on conducting substrates to prepare electrode materials active
      for hydrogen evolution and oxidation with a special emphasis on cobalt diimine
      dioxime complexes and DuBois' nickel diphosphine compounds. We finally discuss
      the optimization required for implementing molecular-engineered materials into
      operational devices and illustrate how such molecular approaches can be expanded
      to other fuel-forming processes such as the electrochemical valorisation of
      carbon dioxide and the oxygen reduction or water oxidation reactions.

PMID- 27711417
TI  - Comment on "Calibration of 57Fe Mossbauer constants by first principles" Phys.
      Chem. Chem. Phys., 2016, 18, 10201-10206.
AB  - The proportionality constant, alpha, between the observed isomer shifts and the
      calculated electron probability density at the iron nucleus has been reevaluated
      in terms of the correct experimental isomer shifts relative to alpha-iron and
      their corresponding accuracy, which should be considered in the linear regression
      fit yielding alpha. The iron-57 excited state nuclear quadrupole moment, Q, is
      not a "relative" value and its widely accepted experimental value is 0.16(1) * 10
      28 m2 as also confirmed by nuclear model calculations.

PMID- 27711418
TI  - From intermolecular interactions to structures and properties of a novel
      cocrystal explosive: a first-principles study.
AB  - By employing a first-principles method, we conducted a thorough study on a novel
      cocrystal explosive 1 : 1 NTO : TZTN and gained insight into the interaction
      structure-property interrelationship. Mulliken bond orders, Hirshfeld surfaces,
      intermolecular binding energies, packing coefficients, and oxygen balance were
      calculated to analyze the intermolecular interactions and structures of the
      cocrystal explosive. The cocrystallization of NTO and TZTN molecules enhances the
      intermolecular binding force, which drives the synthesis of the cocrystal.
      However, the cocrystallization decreases the molecular packing density along the
      closest packed directions, which reduces the density by 10.5% and deteriorates
      the oxygen balance. All of these lead to a reduction in the detonation
      performance compared to NTO explosives. We have also proposed a new method to
      evaluate the impact sensitivity according to the lattice dynamics calculation.
      The cocrystal explosive has a lower impact sensitivity than TZTN but higher than
      NTO, which agrees well with experiments.

PMID- 27711419
TI  - Interface engineering via an insulating polymer for highly efficient and
      environmentally stable perovskite solar cells.
AB  - A tunnelling contact of polystyrene nanofilm was introduced for the first time at
      the interface of perovskite/hole transfer layer, leading to a significantly
      reduced charge recombination. Moreover, such a polymeric contact worked as a
      hydrophobic encapsulation layer for effectively protecting the perovskite against
      humidity. The resultant PSCs displayed a peak efficiency of 17.80% (vs. 15.90% of
      the control cell) and an enhanced stability.

PMID- 27711420
TI  - A binary catalyst system of a cationic Ru-CNC pincer complex with an alkali metal
      salt for selective hydroboration of carbon dioxide.
AB  - Binary catalyst systems comprising a cationic Ru-CNC pincer complex and an alkali
      metal salt were developed for selective hydroboration of CO2 utilizing
      pinacolborane at r.t. and 1 atm CO2, with the combination of
      [Ru(CNCBn)(CO)2(H)][PF6] and KOCO2tBu producing formoxyborane in 76% yield. A
      bicyclic catalytic mechanism was proposed and discussed.

PMID- 27711421
TI  - Local, solvation pressures and conformational changes in ethylenediamine aqueous
      solutions probed using Raman spectroscopy.
AB  - Raman spectra of 1,2-ethylenediamine (EDA) in aqueous solutions are used to
      demonstrate that EDA molecules experience an anti-gauche conformational change
      resulting from the interactions with water. The observed Raman shift reveals a
      compressive (hydrophobic) effect of water on both methylene and amino groups of
      EDA. Raman spectra of EDA at high pressures are used as reference to quantify the
      intermolecular EDA-H2O interactions in terms of local pressures. These results
      are compared with macroscopic solvation pressures calculated from the cohesive
      energy parameter. We compare and discuss all our observations with available
      computational and experimental studies.

PMID- 27711422
TI  - Understanding the surface segregation behavior of transition metals on Ni(111): a
      first-principles study.
AB  - The surface composition of an alloying system has an important impact on its
      catalytic and chemical properties. The segregation behavior of 3d, 4d and 5d
      transition metals on an Ni(111) surface has been investigated by performing first
      principles calculations in the framework of density-functional theory with the
      generalized gradient approximation for the exchange-correlation functional. Our
      calculated surface segregation energies are in good agreement with the
      experimental data as well as with previous calculated results. Most importantly,
      we have made an attempt to correlate the surface segregation behavior with the
      surface energy difference between the alloying (solute) metal and the host metal,
      the elastic energy release, and the heat of solution of the alloying metal in the
      host metal. By doing so, we not only overcome the difficulties that empirical
      models encounter, but also clearly identify the importance of each contribution
      to the segregation behavior of an alloying metal. The present study provides
      valuable insight into the surface segregation behavior of solute atoms in
      alloying systems.

PMID- 27711423
TI  - Domain-dependent electronic structure and optical absorption property in hybrid
      organic-inorganic perovskite.
AB  - Hybrid organic-inorganic perovskites, represented by materials in the CH3NH3PbI3
      series, have become one of the most promising materials for solar cells with a
      high power conversion efficiency and low cost. The ordered Pb-I cage in such
      hybrid perovskites can induce the polarized cations to form a variety of
      polarization domains with long-range order, which will lead to the formation of
      specific atomic conformations or metastable crystalline phases, unique electronic
      band structures and optical absorption properties. Such domain-dependent
      characteristics play a critical role in the phase transition and service
      stability of such solar cells, and also open up the opportunity of tuning their
      electronic structure. In the present study, we systematically investigate the
      band structures and optical absorption properties of different electronically
      ordered domains in CH3NH3PbI3. By comparing different perovskites containing
      various cations, we have clarified the important influence of cation polarization
      on domain-dependent properties. Our results provide not only a possible pathway
      for the manipulation of band structure by applying an external field, but also a
      novel scheme for improving the performance and stability of hybrid perovskites.

PMID- 27711424
TI  - DFT global optimisation of gas-phase and MgO-supported sub-nanometre AuPd
      clusters.
AB  - The Birmingham Parallel Genetic Algorithm (BPGA) has been adopted for the global
      optimization of free and MgO(100)-supported Pd, Au and AuPd nanocluster
      structures, over the size range N = 4-10. Structures were evaluated directly
      using density functional theory, which has allowed the identification of Pd, Au
      and AuPd global minima. The energetics, structures, and tendency of segregation
      have been evaluated by different stability criteria such as binding energy,
      excess energy, second difference in energy, and adsorption energy. The ability of
      the approach in searching for putative global minimum has been assessed against a
      systematic homotop search method, which shows a high degree of success.

PMID- 27711426
TI  - The structure of Pyrex(r) glass investigated by correlation NMR spectroscopy.
AB  - The structure of the important technological glass Pyrex(r) was investigated by
      1D- and 2D-correlation NMR techniques. Its local order was analysed in a first
      step by 1D 23Na, 27Al, 11B and 29Si MAS-NMR performed at 9.4 and 18.8 T. In a
      second step, its medium range order was documented using homo- and, for the first
      time, hetero-nuclear correlation NMR techniques: (i) the presence and the nature
      of BOB bonds were analysed using 2D 11B DQ-SQ map; (ii) the silicate speciation
      was probed using 2D 29Si/X (X = 11B, 23Na and 27Al) D-HMQC maps and (iii) the
      27Al/11B interaction was studied using TRAPDOR-NMR experiments. Altogether, the
      set of NMR data was used to extract accurate NMR parameters, to rule out the
      presence of diborate and danburite superstructural units and to provide an
      updated structural model based on B3 based groups attached to a T4 network (T =
      Si, B, Al).

PMID- 27711425
TI  - Hydrogen evolution from water using Mo-oxide clusters in the gas phase: DFT
      modeling of a complete catalytic cycle using a Mo2O4-/Mo2O5- cluster couple.
AB  - Density functional theory (DFT) calculations using a small metal cluster couple,
      Mo2O4-/Mo2O5-, are used to model a complete catalytic cycle for H2 production
      from water. While Mo2O4- is known to readily react with water to form Mo2O5- and
      release H2, the principal challenge is in reducing Mo2O5- to Mo2O4- to complete
      the cycle. We investigate the role of several potential sacrificial reagents
      (ethylene, propylene, CO and acetylene) that can reduce Mo2O5- after the initial
      oxidation. DFT calculations of the free energy reaction pathways demonstrate the
      presence of overall kinetically accessible barriers that are below the entrance
      channel (separated reactants) in the Mo2O4- + H2O reaction (step I) followed by
      the Mo2O5- + sacrificial reagent reactions (step II). Though the overall reaction
      is thermodynamically favorable, the first step is highly exothermic while the
      second step is endothermic. The deepest part of the potential energy surface is a
      complex of Mo2O5- with the sacrificial reagent. If the energy gained in the first
      reaction and the succeeding complex formation is not lost due to collisions, the
      subsequent barriers can be overcome, leading to possible catalytic applications
      of the Mo2O4-/Mo2O5- cluster couple in H2 production reactions.

PMID- 27711428
TI  - Solid-state valence tautomeric octahedral {CoII[(BQ-N-Cat)]2}0 complex formation
      via ligand-centered phenolic C-O bond breaking and Co-O bond making.
AB  - Ligand H4LO(AP/AP) underwent ligand-centered C-O bond cleavage during a
      complexation reaction with Co(ii)-salt. The thus formed octahedral {CoII[(BQ-N
      Cat)]2}0 complex showed valence tautomerization in the solid state. While the
      process was triggered by the presence of lattice solvent, the nature of the
      solvent molecule has less effect on the process.

PMID- 27711427
TI  - Mechanistical investigation on the self-enhanced photocatalytic activity of
      CuO/Cu2O hybrid nanostructures by density functional theory calculations.
AB  - The photocatalytic mechanism of a Cu2O/CuO hybrid system is disclosed in detail
      by density functional theory (DFT) calculations. The synergistic relationship of
      the two counterparts is confirmed by hydrogen peroxide (H2O2) formation on the
      CuO nanowires and dissociation on the Cu2O nanoparticles; this enables the system
      to self-sufficiently produce hydroxyl radicals, which is highly efficient in the
      photocatalytic degradation of methyl orange. The exposed surfaces are found to be
      crucial in the cooperative photocatalytic system, especially the Cu2O(111)
      surface, in the dissociation of H2O2. The distinct positions of the conduction
      band minimum and valence band maximum for CuO and Cu2O and synergic surface
      reactions enable the effective utilization of the electrons and holes generated
      by visible-light irradiation. Our results will contribute to a greater
      understanding of the specific mechanism of photodegradation catalyzed by Cu2O/CuO
      heterostructures, which may lead to promising directions in structure
      optimization for photocatalysts with high photocatalytic efficiency.

PMID- 27711429
TI  - An alcohol-soluble and ion-free electron transporting material functionalized
      with phosphonate groups for solution-processed multilayer PLEDs.
AB  - An alcohol-soluble and ion-free small molecule TPPO functionalized with
      phosphonate groups has been developed as the electron transporting material for
      multilayer PLEDs fabricated via an orthogonal solvent strategy. A state-of-art
      current efficiency as high as 11.6 cd A-1 is achieved, which is about 16 times
      higher than that of the single-layer device without TPPO (0.7 cd A-1).

PMID- 27711430
TI  - Water dissociation on MnO(1 * 1)/Ag(100).
AB  - In this work we utilize experimental and simulation techniques to examine the
      molecular level interaction of water with a MnO(1 * 1) thin film deposited onto
      Ag(100). The formation of MnO(1 * 1)/Ag(100) was characterized by low energy
      electron diffraction and scanning tunneling microscopy. Density functional theory
      (DFT) shows MnO(1 * 1) is thermodynamically more stable than MnO(2 * 1) by ~0.4
      eV per MnO. Upon exposure to 2.5 Torr water vapor at room temperature, X-ray
      photoemission spectroscopy results show extensive surface hydroxylation
      attributed to reactivity at MnO(1 * 1) terrace sites. DFT calculations of a water
      monomer on MnO(1 * 1)/Ag(100) show the dissociated form is energetically more
      favorable than molecular adsorption, with a hydroxylation activation barrier 0.4
      eV per H2O. These results are discussed and contrasted with previous studies of
      MgO/Ag(100) which show a stark difference in behavior for water dissociation.

PMID- 27711431
TI  - Phase transition in crown-jewel structured Au-Ir nanoalloys with different
      shapes: a molecular dynamics study.
AB  - We have studied the melting process for crown-jewel structured Ir55, Ir54Au,
      Ir43Au12, Ir25Au30, Ir13Au42, and Au55 nanoclusters in the icosahedral, Ir55,
      Ir54Au, Ir43Au12, Ir19Au36, Ir13Au42, and Au55 nanoclusters in the cuboctahedral,
      and Ir54, Ir53Au, Ir47Au7, Ir17Au37, Ir7Au47, and Au54 nanoclusters in the
      decahedral morphologies. We have investigated the different thermodynamic,
      structural, and dynamical properties for the different nanoclusters in the
      different structures. Our thermodynamic results indicated that as the
      concentration of Au atoms in the nanoclusters increases, the absolute value of
      internal energy, and so the melting points, of the nanoclusters decrease. It is
      also shown that the Au atoms decrease the melting temperature of the pure
      cuboctahedral cluster more than that of the other structures. We have also found
      that the Au atoms were located in favorable positions at the surface sites of
      nanoalloys. Also, the doping of the Ir nanocluster by Au atoms makes the cluster
      more stable. It is also found that nanoclusters with different morphologies have
      almost the same stability. Our structural results indicated that after the
      melting process, the Au atoms generally tend to lie in the outer shell of the
      cluster, but the Ir atoms generally tend to lie in the core of the cluster (see
      the Ir13Au42 and Ir7Au47 nanoclusters, for example). We have also found the
      interesting result that the Ir7Au47 nanocluster shows a solid-solid transition
      from a decahedral structure to an icosahedral structure before melting. The
      Ir43Au12 nanocluster also shows a transformation from a cuboctahedral structure
      to an icosahedral-like structure before melting. Our dynamical results showed
      that doping of the Ir55 cluster with an Au atom sharply increases the self
      diffusion coefficient in the initial state in the solid phase, especially in
      icosahedral and cuboctahedral structures. It is also shown that the Ir13Au42
      cluster in icosahedral and cuboctahedral and the Ir7Au47 and Ir17Au37 clusters in
      decahedral morphologies have smaller values of self-diffusion coefficients than
      other clusters after the melting point and that this could be due to the
      formation of core-shell structures.

PMID- 27711432
TI  - Water desalination by electrical resonance inside carbon nanotubes.
AB  - Although previous studies have indicated that the carbon nanotube (CNT) can be
      used for directed transportation of water and ions, it is still a challenging
      problem to design a CNT-based device for high performance water desalination. In
      this study, by using molecular dynamics simulations, we successfully design one
      type of CNT as a highly efficient desalination membrane through electrical
      resonance. By decorating the two ends of the CNT with vibrational charges, an
      alternating electric field is created inside the CNT. When the amplitude of the
      vibrational charge is 0.05 e, and the vibrational frequency is between 10 THz and
      20 THz, the CNT can completely block the transportation of ions. The decrease of
      the amplitude or the deviation of the frequency in an appropriate range will
      gradually increase the ion flow. Besides, we also reveal the underlying molecular
      mechanism of ion blockage, i.e., the electric resonance can disrupt the water
      structure inside the CNT and then alter the hydration energy of ions inside the
      CNT. More importantly, we further demonstrate that this mechanism is universal,
      which is independent of the type of ions and the size of CNT. The present work
      could be useful for designing water desalination membranes with lower energy
      consumption and higher fresh water production.

PMID- 27711433
TI  - Programmed photosensitizer conjugated supramolecular nanocarriers with dual
      targeting ability for enhanced photodynamic therapy.
AB  - A programmed supramolecular nanocarrier was developed for multistage targeted
      photodynamic therapy. This smart nanocarrier exhibited enhanced cellular uptake
      and controlled mitochondria targeting, as well as an excellent photodynamic
      therapeutic effect after light irradiation.

PMID- 27711434
TI  - The divide-and-conquer second-order proton propagator method based on nuclear
      orbital plus molecular orbital theory for the efficient computation of proton
      binding energies.
AB  - An efficient computational method to evaluate the binding energies of many
      protons in large systems was developed. Proton binding energy is calculated as a
      corrected nuclear orbital energy using the second-order proton propagator method,
      which is based on nuclear orbital plus molecular orbital theory. In the present
      scheme, the divide-and-conquer technique was applied to utilize local molecular
      orbitals. This use relies on the locality of electronic relaxation after
      deprotonation and the electron-nucleus correlation. Numerical assessment showed
      reduction in computational cost without the loss of accuracy. An initial
      application to model a protein resulted in reasonable binding energies that were
      in accordance with the electrostatic environment and solvent effects.

PMID- 27711435
TI  - A MOF-membrane based on the covalent bonding driven assembly of a NMOF with an
      organic oligomer and its application in membrane reactors.
AB  - A UiO-66-MOF-based membrane UiO-66-TEM (1) was prepared by the assembly of
      methacrylamide-decorated UiO-66-NH-Met with a thiol side chain-attached
      polysiloxane (PSI-SH) via a photoinduced thiol-ene click reaction. The obtained
      membrane 1 can be a platform to support Au nanoparticles (Au NPs) to generate an
      Au-MOF-polymer composite membrane Au@UiO-66-TEM (2). 1 and 2 can be used to build
      highly efficient continuous flow-through membrane reactors for Knoevenagel
      condensation of 4-nitrobenzaldehyde with malononitrile and 4-nitrophenol (4-NP)
      reduction at ambient temperature, respectively.

PMID- 27711436
TI  - Palladium-catalyzed Sonogashira coupling of amides: access to ynones via C-N bond
      cleavage.
AB  - The first palladium-catalyzed Sonogashira coupling of amides has been developed,
      which proceeds via a selective cleavage of the N-acylsaccharin C-N bond. Notably,
      the new approach employs N-acylsaccharins as coupling partners to give ynones in
      good to excellent yield. This protocol can be efficiently utilized in the
      synthesis of a broad array of ynones under low catalyst loading and Cu-free
      conditions.

PMID- 27711437
TI  - Microsecond and nanosecond polyproline II helix formation in aqueous nanodrops
      measured by mass spectrometry.
AB  - The 1.5 MUs and <400 ns time constants for the formation of polyproline II helix
      structures in 21 and 16 residue peptides, respectively, are measured using rapid
      mixing from theta-glass emitters coupled with mass spectrometry. Results from
      these studies should serve as useful benchmarks for comparison with computational
      simulation results.

PMID- 27711438
TI  - Preparation and structure of Fe-containing aluminosilicate thin films.
AB  - In attempts to fabricate model systems of Fe-containing aluminosilicates, we
      studied the incorporation of iron into silicate and aluminosilicate bilayer films
      grown on Ru(0001). Structural characterization was performed by low energy
      electron diffraction, X-ray photoelectron spectroscopy, infrared reflection
      absorption spectroscopy and scanning tunneling microscopy. The experimental
      results show that even at low concentrations Fe does not randomly substitute
      Si(Al) cations in the silicate framework, but segregates into a pure silicate
      (aluminosilicate) phase and an Fe-silicate phase which is formed by an FeO(111)
      like layer underneath a silicate layer. At high Fe/(Si + Al) molar ratios, the
      resulting films showed two phases depending on the annealing temperature. In both
      phases, the surface exposes a silicate layer and the bottom layer is dominated by
      FeO. The Al ions seem to be present in the bottom layer at relatively low
      oxidation temperatures, but segregate as alumina clusters at the surface at
      higher temperatures. The results suggest that the formation of in-frame Fe
      species in silicalites and zeolites is thermodynamically unfavourable. This study
      provides further steps towards the rational design of model systems for studying
      surface chemistry of a wide class of layered minerals.

PMID- 27711439
TI  - A supramolecular fluorescent vesicle based on a coordinating aggregation induced
      emission amphiphile: insight into the role of electrical charge in cancer cell
      division.
AB  - Binding of Zn2+ to the coordinating supramolecular vesicle based on an
      aggregation induced emission amphiphile TPE-BPA immediately triggers the
      formation of charged vesicles. This induces vesicle fission and fluorescence
      reduction, suggesting a looser molecular packing in the charged vesicle membrane.
      Since cancer cells are highly charged, this indicates that the quick fission of
      cancer cells may have electrical charge origin.

PMID- 27711440
TI  - Multivalent effect of glycopolypeptide based nanoparticles for galectin binding.
AB  - Synthetic glycopolypeptides are versatile glycopolymers used to conceive
      bioinspired nanoassemblies. In this work, novel amphiphilic glycopolypeptides
      were designed to incorporate lactose or galactan in order to prepare polymeric
      nanoassemblies with sizes below 50 nm. The bioactivity of the two different outer
      surface sugar units was evaluated by defining glycan relative binding affinities
      to human galectins 1 and 3. A specific multivalent effect was found only for
      polymeric nanoparticles displaying galactan with a significant increase of the
      binding activity as compared to free glycan in solution. Such synthetic designs
      present great potential as therapeutic tools to address galectin related
      pathologies.

PMID- 27711441
TI  - Unexpectedly high activity of bare alumina for non-oxidative isobutane
      dehydrogenation.
AB  - Bare alumina shows surprisingly high activity in non-oxidative dehydrogenation of
      isobutane to isobutylene. The activity is related to surface coordinatively
      unsaturated Al sites (Alcus), which are created upon removal of OH groups during
      alumina treatment at high temperatures. Alcus and neighbouring lattice oxygen
      represent the active site for isobutane dehydrogenation.

PMID- 27711442
TI  - Effects of atomic interaction stiffness on low-temperature relaxation of
      amorphous solids.
AB  - While low-temperature relaxations show significant differences among metallic
      glasses with different compositions, the underlying mechanism remains mysterious.
      Using molecular dynamics simulation, low-temperature relaxation of amorphous
      solids is investigated in model systems with different atomic interaction
      stiffness. It was found that as the interaction stiffness increases, the low
      temperature relaxation is enhanced. The fraction of mobile atoms increases with
      increasing interaction stiffness, while the length scale of dynamical
      heterogeneity does not change. The enhanced relaxation may be due to increased
      dynamical heterogeneity. These findings provide a physical picture for better
      understanding the origin of low-temperature relaxation dynamics in amorphous
      solids, and the experimentally observed different beta-relaxation behaviors in
      various metallic glasses.

PMID- 27711443
TI  - Acidity constants and redox potentials of uranyl ions in hydrothermal solutions.
AB  - We report a first principles molecular dynamics (FPMD) study of the structures,
      acidity constants (pKa) and redox potentials (E0) of uranyl (UO22+) from ambient
      conditions to 573 K. It is found that UO22+ keeps five coordination up to 573 K
      whereas UO2+ transforms from 5 to 4-coordinate as temperature increases to 573 K.
      The FPMD-based vertical energy gap method is used to derive pKas and E0s. The
      method is validated by comparing with available experimental data (for E0 under
      the ambient conditions and for pKas from ambient conditions to 367 K), with an
      uncertainty of 1-2 pKa units and 0.2 V for pKa and E0. The encouraging results
      demonstrate that the method may be used to predict the pH-Eh diagrams of f-block
      elements under the conditions of hydrothermal solutions. The results show that
      the acidity constants of uranyl decrease with temperature and are lower than 3.0
      when the temperature is above 473 K, indicating that hydrolytic forms are
      dominant for U(vi) in the near neutral pH range. The reduction potential
      increases with temperature, indicating that the reduced state is more significant
      at higher temperatures.

PMID- 27711444
TI  - A multifunctional material of two-dimensional g-C4N3/graphene bilayer.
AB  - Using first-principles calculations, we present a multifunctional material of g
      C4N3/graphene bilayer with great potentials in the field of spintronics and
      photocatalysis. In g-C4N3/graphene bilayer, N atoms create localized spin
      polarization and p-doped graphene shows high charge carrier density, which makes
      this nanocomposite a perfect candidate for spintronic applications. Meanwhile,
      the charge redistribution occurred between the two layers also facilitates the
      separation of photogenerated electron-hole pairs. Moreover, the inclusion of C
      atoms into g-C3N4 closes the band gap of g-C3N4/graphene completely and induces
      more levels near the Fermi energy, and thus the g-C4N3/graphene bilayer displays
      enhanced visible light absorption compared to the g-C3N4/graphene bilayer.

PMID- 27711446
TI  - Experimental and computational studies of the roles of MgO and Zn in talc for the
      selective formation of 1,3-butadiene in the conversion of ethanol.
AB  - The one-step conversion of ethanol to 1,3-butadiene was performed using talc
      containing Zn (talc/Zn) as a catalyst. The influence of the MgO and Zn in the
      talc on the formation rate and selectivity for 1,3-butadiene were investigated.
      MgO as a catalyst afforded 1,3-butadiene with a selectivity that was nearly the
      same as talc/Zn at ~40% ethanol conversion at 673 K, although the rate of 1,3
      butadiene formation over MgO was about 40 times lower than that over the talc/Zn.
      The introduced Zn cations were located in octahedral sites in place of Mg cations
      in the talc lattice. The Zn cations accelerated the rate of CH3CHO formation from
      ethanol, resulting in an increase in the rate of 1,3-butadiene formation.
      However, the rate of CH3CHO consumption to form crotonaldehyde was not influenced
      by Zn, although the distribution of crotonaldehyde was decreased with increasing
      Zn concentrations. X-ray photoelectron spectra of talc/Zn showed that the O1s
      binding energy was increased by increasing the concentration of Zn, while those
      of both Mg2p and Si2p were hardly influenced. DFT calculations were used to
      estimate the atomic charges on the O, Mg, Si, and Zn atoms when an atom of Zn per
      unit cell of talc was introduced into an octahedral site. On the basis of the
      results for the conversion of ethanol into 1,3-butadiene and the corresponding
      DFT calculations, the roles of the O, Zn, Mg, and Si atoms in the talc catalyst
      for the formation of 1,3-butadiene from ethanol were discussed.

PMID- 27711447
TI  - Pyrite surface environment drives molecular adsorption: cystine on pyrite(100)
      investigated by X-ray photoemission spectroscopy and low energy electron
      diffraction.
AB  - We have demonstrated that the annealing process for cleaning pyrite surfaces is a
      critical parameter in promoting ordering on the surface and driving surface
      reactivity. Furthermore, we describe a spectroscopic surface characterization of
      the presence or absence of the surface ordering, as indicated by the Low Energy
      Electron Diffraction (LEED) pattern, as a function of the surface annealing
      process. Complementary X-ray photoemission spectroscopy (XPS) results provide
      evidence that longer annealing processes of over 3 hours repair the sulfur
      vacancies in the pyrite, making FeS species partially disappear in favor of FeS2
      species. These features play an important role in molecular adsorption. We show
      that in the case of the cystine amino acid on the (100) pyrite surface, the
      substrate structure is responsible for the chemical adsorption form. The presence
      of an ordered structure on the surface, as indicated by the LEED pattern, favors
      the cystine NH3+ chemical form, whereas the absence of the surface ordering
      promotes cystine NH2 adsorption due to the sulfur-deficient surface. The cystine
      molecule could then act by changing its chemical functionalities to compensate
      for the iron surface coordination. The chemical molecular adsorption form can be
      selected by the surface annealing conditions, implying that environmental
      conditions could drive molecular adsorption on mineral surfaces. These findings
      are relevant in several surface processes, and they could play a possible role in
      prebiotic chemistry surface reactions and iron-sulfur scenarios.

PMID- 27711445
TI  - Structures of the kinetically trapped i-motif DNA intermediates.
AB  - In the present work, the conformational dynamics and folding pathways of i-motif
      DNA were studied in solution and in the gas-phase as a function of the solution
      pH conditions using circular dichroism (CD), photoacoustic calorimetry analysis
      (PAC), trapped ion mobility spectrometry-mass spectrometry (TIMS-MS), and
      molecular dynamics (MD). Solution studies showed at thermodynamic equilibrium the
      existence of a two-state folding mechanism, whereas during the pH = 7.0 -> 4.5
      transition a fast and slow phase (DeltaHfast + DeltaHslow = 43 +/- 7 kcal mol-1)
      with a volume change associated with the formation of hemiprotonated cytosine
      base pairs and concomitant collapse of the i-motif oligonucleotide into a compact
      conformation were observed. TIMS-MS experiments showed that gas-phase,
      kinetically trapped i-motif DNA intermediates produced by nanoESI are preserved,
      with relative abundances depending on the solution pH conditions. In particular,
      a folded i-motif DNA structure was observed in nanoESI-TIMS-MS for low charge
      states in both positive and negative ion mode (e.g., z = +/-3 to +/-5) at low pH
      conditions. As solution pH increases, the cytosine neutralization leads to the
      loss of cytosine-cytosine+ (C.CH+) base pairing in the CCC strands and in those
      conditions we observe partially unfolded i-motif DNA conformations in nanoESI
      TIMS-MS for higher charge states (e.g., z = -6 to -9). Collisional induced
      activation prior to TIMS-MS showed the existence of multiple local free energy
      minima, associated with the i-motif DNA unfolding at z = -6 charge state. For the
      first time, candidate gas-phase structures are proposed based on mobility
      measurements of the i-motif DNA unfolding pathway. Moreover, the inspection of
      partially unfolded i-motif DNA structures (z = -7 and z = -8 charge states)
      showed that the presence of inner cations may or may not induce conformational
      changes in the gas-phase. For example, incorporation of ammonium adducts does not
      lead to major conformational changes while sodium adducts may lead to the
      formation of sodium mediated bonds between two negatively charged sides inducing
      the stabilization towards more compact structures in new local, free energy
      minima in the gas-phase.

PMID- 27711448
TI  - Delayed ignition and propulsion of catalytic microrockets based on fuel-induced
      chemical dealloying of the inner alloy layer.
AB  - The delayed ignition and propulsion of catalytic tubular microrockets based on
      fuel-induced chemical dealloying of an inner alloy layer is demonstrated. Such
      timed delay motor activation process relies on the preferential gradual corrosion
      of Cu from the inner Pt-Cu alloy layer by the peroxide fuel. The dealloying
      process exposes the catalytically active Pt surface to the chemical fuel, thus
      igniting the microrockets propulsion autonomously without external stimuli. The
      delayed motor activation relies solely on the intrinsic material properties of
      the micromotor and the surrounding solution. The motor activation time can thus
      be tailored by controlling the composition of the Cu-Pt alloy layer and the
      surrounding media, including the fuel and NaCl concentrations and local pH. Speed
      acceleration in a given fuel solution is also demonstrated and reflects the
      continuous exposure of the Pt surface. The versatile "blastoff" control of these
      chemical microrockets holds considerable promise for designing self-regulated
      chemically-powered nanomachines with a "built-in" activation mechanism for
      diverse tasks.

PMID- 27711449
TI  - A perspective on structural and computational work on collagen.
AB  - Collagen is the single most abundant protein in the extracellular matrix in the
      animal kingdom, with remarkable structural and functional diversity and regarded
      one of the most useful biomaterials. Etymologically, the term collagen comes from
      Greek kola 'glue' and gen 'giving birth to'. Thus, it is not surprising that the
      various collagens and the structures they form all serve the same purpose, to
      help tissues withstand stretching. Among the functions the various collagens are
      involved in are cell adhesion and migration, tissue repair, scaffolding and
      morphogenesis. Thus knowledge about the structure and properties of collagen, how
      they change depending on the nature of the local environment as well as the
      nature and specificity of collagen interactions with its partners is central to
      discerning the role of collagen in medical applications such as imaging, drug
      delivery and tissue engineering, and in the design and construction of synthetic
      collagen-like materials for tools in biomaterial science and nanotechnology. The
      main focus of this perspective is to review the molecular and packing structures
      of collagen and the computer simulations work performed up to now to further
      highlight the significance of collagen.

PMID- 27711450
TI  - The Z-enoate assisted, Meyer-Schuster rearrangement cascade: unconventional
      synthesis of alpha-arylenone esters.
AB  - Bronsted acid promoted nucleophilation of propargylic alcohols during the Meyer
      Schuster rearrangement (M-S) has been introduced. A novel concept of reverse
      polarization of the M-S intermediate allenyl cation has been realized by
      employing a cis-enoate assisted strategy. This idea is well demonstrated by the
      metal free synthesis of complex, highly functionalized cyclic as well as acyclic
      alpha-arylenones. The synthetic importance of the derived products was
      highlighted by the efficient conversion to biologically relevant molecules such
      as pyrazoles and 4,5-seco-abietane.

PMID- 27711451
TI  - Pt38 cluster on OH- and COOH-functionalised graphene as a model for Pt/C
      catalysts.
AB  - The binding of a Pt38-cluster on pristine graphene, mono-vacancy graphene, OH-
      and COOH-functionalised graphene has been investigated using DFT-calculations.
      Graphene containing a mono-vacancy site or OH and COOH functional groups on
      graphene anchor the Pt38-cluster more strongly than pristine graphene. The most
      favoured adsorption geometry for the cluster depends on the number of Pt-C bonds
      generated and the required distortion of the interacting facet. Adsorption of the
      cluster is associated with charge transfer between (functionalised) graphene and
      the Pt38-cluster, a localised charge re-distribution within the cluster and shift
      in the d-band centre. The modified electronic properties of the supported Pt38
      cluster would imply a change in the reactivity of these supported Pt38-clusters
      towards adsorbates depending on the type of defect present in the support.

PMID- 27711452
TI  - Electronic structure and energy decomposition analyses as a tool to interpret the
      redox potential ranking of naphtho-, biphenyl- and biphenylene-quinone isomers.
AB  - By calling on modelling approaches we have performed a comparative study on the
      redox properties of various naphtho-, biphenyl- and biphenylene-quinone isomers.
      These different compounds exhibit as a whole a redox potential range between 2.09
      and 2.90 V vs. Li+/Li. A specific methodology was used to decrypt the interplay
      among isomerism, aromaticity and antiaromaticity modifications and the
      stabilization/destabilization effects due to other molecular components on this
      key electrochemical feature for electrode materials of batteries. In particular,
      energy decomposition analysis, within the Quantum Theory of Atoms in Molecules,
      along with the electron and electron spin population changes upon reduction
      nicely rationalise the observed potential trends. While 1,2- and 2,3-isomers show
      the highest/lowest redox potential in the biphenylene-quinone series, a reverse
      trend is observed for the naphtho-quinone, the compound having the two carbonyl
      groups on distinct rings being characterized by an intermediate value in both
      cases. There is instead almost no differentiation between 1,2 and 2,3 isomers for
      the biphenyl-quinone family.

PMID- 27711453
TI  - Carrier transport behaviors depending on the two orthogonally directional energy
      bands in the ZnO nanofilm affected by oxygen plasma.
AB  - An oxygen plasma treatment of ZnO nanostructures has frequently been used for
      obtaining a desired optoelectrical property. Nevertheless, a detailed study
      regarding carrier transport behaviors affected by the plasma has scarcely been
      managed, especially in the thin film structure, owing to its more complex physics
      than those of a one-dimensional nanostructure. Herein, we demonstrate an analysis
      of carrier transport behaviors on an oxygen plasma-treated ZnO nanofilm (50 nm
      thick) on a SiO2/Si substrate. By comparison with the as-grown sample, we
      observed drastic changes in carrier transport behavior according to the short
      exposure times of 30 s and 60 s. The plasma effect leading to the distinction was
      confirmed to originate from the bombardment of energetic ions near the surface
      and the diffusion of various oxygen ions and radicals into the host. The
      mechanism of the resulting carrier transport was comprehended through the
      revelation of two orthogonally directional energy band structures (surface band
      bending in the surface layer and localized energy bending at the grain boundary).
      Furthermore, we experimentally observed that the increased electrical barrier of
      the grain boundary, due to negatively absorbed oxygen ions, could be helpful in
      impeding persistent photoconductivity and in reducing dark current.

PMID- 27711454
TI  - Calculation of Raman parameters of real-size zigzag (n, 0) single-walled carbon
      nanotubes using finite-size models.
AB  - Structural and selected Raman features of pristine single-walled carbon nanotubes
      (SWCTNs) with diameters from 0.4 to 1.2 nm and total lengths up to 2.15 nm were
      studied using the density functional theory (DFT) at the UB3LYP/6-31G* level.
      Models of different lengths (1, 4, 6 and 10 adjacent bamboo-units) of zigzag (n,
      0) SWCNTs, for n ranging from 5 to 15, were studied. Highly systematic changes of
      individual CC bond lengths and angles along the nanotube axis were observed and
      described for the longest models. Predicted Raman active radial breathing mode
      (RBM) vibrational frequencies regularly decreased upon increasing the nanotube
      diameter and only a negligible effect of the tube length was observed. The
      changes in calculated RBM frequencies with increasing diameter were close to
      values estimated using empirical formulas. The experimental G-mode
      characteristics were reasonably well reproduced using the 4-unit model,
      especially for tubes with the diameter d > 1 nm. Raman features were also
      determined for cyclacenes representing the shortest models of SWCNTs. Calculated
      RBM frequencies of cyclacenes match closely the values for longer SWCNT models
      but are too inaccurate in the case of the G-mode. For the first time, the Raman
      properties of SWCNTs were also determined using the Cartesian coordinate tensor
      (CCT) transfer technique, thus providing reasonable frequencies of Raman active
      bands for long tubes consisting of 10 bamboo-units.

PMID- 27711455
TI  - Crystal engineering of a zwitterionic drug to neutral cocrystals: a general
      solution for floxacins.
AB  - The transformation of zwitterionic Sparfloxacin (SPX) to the neutral form is
      achieved by cocrystallization. Neutral forms of drugs are important for higher
      membrane permeability, while zwitterions are more soluble in water. The twin
      advantages of higher solubility/dissolution rate and good stability of neutral
      SPX are achieved in a molecular cocrystal compared to its zwitterionic SPX
      hydrate. The amine-phenol supramolecular synthon drives cocrystal formation, with
      the paraben ester acting as a "proton migrator" for the ionic to neutral
      transformation.

PMID- 27711456
TI  - Two-dimensional dual-pore covalent organic frameworks obtained from the
      combination of two D2h symmetrical building blocks.
AB  - A strategy to construct covalent organic frameworks (COFs) bearing two different
      kinds of pores has been developed, by which two dual-pore COFs were fabricated
      through the condensation reactions of two D2h symmetrical building blocks. The
      COFs exhibit good adsorption capacities for CO2 and H2.

PMID- 27711457
TI  - Pushing up the magnetisation values for iron oxide nanoparticles via zinc doping:
      X-ray studies on the particle's sub-nano structure of different synthesis routes.
AB  - The maximum magnetisation (saturation magnetisation) obtainable for iron oxide
      nanoparticles can be increased by doping the nanocrystals with non-magnetic
      elements such as zinc. Herein, we closely study how only slightly different
      synthesis approaches towards such doped nanoparticles strongly influence the
      resulting sub-nano/atomic structure. We compare two co-precipitation approaches,
      where we only vary the base (NaOH versus NH3), and a thermal decomposition route.
      These methods are the most commonly applied ones for synthesising doped iron
      oxide nanoparticles. The measurable magnetisation change upon zinc doping is
      about the same for all systems. However, the sub-nano structure, which we studied
      with Mossbauer and X-ray absorption near edge spectroscopy, differs tremendously.
      We found evidence that a much more complex picture has to be drawn regarding what
      happens upon Zn doping compared to what textbooks tell us about the mechanism.
      Our work demonstrates that it is crucial to study the obtained structures very
      precisely when "playing" with the atomic order in iron oxide nanocrystals.

PMID- 27711458
TI  - Mechanical responses of borophene sheets: a first-principles study.
AB  - Recent experimental advances for the fabrication of various borophene sheets
      introduced new structures with a wide range of applications. Borophene is the
      boron atom analogue of graphene. Borophene exhibits various structural polymorphs
      all of which are metallic. In this work, we employed first-principles density
      functional theory calculations to investigate the mechanical properties of five
      different single-layer borophene sheets. In particular, we analyzed the effect of
      the loading direction and point vacancy on the mechanical response of borophene.
      Moreover, we compared the thermal stabilities of the considered borophene
      systems. Based on the results of our modelling, borophene films depending on the
      atomic configurations and the loading direction can yield a remarkable elastic
      modulus in the range of 163-382 GPa nm and a high ultimate tensile strength from
      13.5 GPa nm to around 22.8 GPa nm at the corresponding strain from 0.1 to 0.21.
      Our study reveals the remarkable mechanical characteristics of borophene films.

PMID- 27711459
TI  - Dioxygen-induced oxidative activation of a P-H bond: radical oxyphosphorylation
      of alkenes and alkynes toward beta-oxy phosphonates.
AB  - The dioxygen-induced radical oxyphosphorylation of alkenes and alkynes is
      presented, wherein a P-H bond was activated by molecular oxygen. Various beta-oxy
      phosphonates could be facilely synthesized without the assistance of any
      transition metals or extra organic initiators. Mechanistic studies showed that
      HP(O)Ph2 acts as a reductant to accelerate oxyphosphorylation.

PMID- 27711460
TI  - Influence of the mixed organic cation ratio in lead iodide based perovskite on
      the performance of solar cells.
AB  - Lead halide based perovskite solar cells are presently the flagship among the
      third generation solution-processed photovoltaic technologies. The organic cation
      part in the perovskite plays an important role in terms of crystal structure
      tuning from tetragonal to trigonal or pseudocubic or vice versa depending on the
      organic cations used, while it also displays different microstructure. In this
      paper, we demonstrate the influence of the organic cation part with respect to
      optical properties, hysteresis behavior, and stability. This study offers a clear
      understanding of the perovskite properties and how they can be modulated by
      compositional engineering. With a rational choice, light harvesting abilities and
      hysteresis behavior can be controlled in these systems. The substitution of
      formamidinium cation by methylammonium cation allows achieving low temperature
      annealing and inducing stability in perovskites together with enhanced
      photovoltaic properties. By the use of in-situ scanning force microscopy
      experiments the conversion of precursors to perovskite at a particular
      temperature can be visualized.

PMID- 27711461
TI  - A joint experimental and theoretical determination of the structure of discharge
      products in Na-SO2 batteries.
AB  - Na-SO2 batteries are promising power sources for energy storage systems. However,
      it is unclear what happens on the cathode surface at the molecular level during
      the discharge process. Here, we provide the working mechanism of Na-SO2 batteries
      through a combination of nuclear magnetic resonance (NMR) spectroscopy and first
      principles NMR calculations.

PMID- 27711462
TI  - Deciphering the cryptic role of a catalytic electron in a photochemical bond
      dissociation using excited state aromaticity markers.
AB  - The breaking of bonds by catalytic electrons has gained prominence very recently
      but has been limited to cases where electrons from external sources have been
      used. Here, we show that upon photoexcitation, an electron of intramolecular
      origin is transferred from one part of a molecule to another followed by bond
      cleavage and then returns to its original moiety on completion of its catalytic
      function. By a proper assessment of the dramatic changes in aromaticity in
      excited-state intermediates along the photoreaction coordinate captured by the
      magnetically induced current density (MICD) technique, we show that in 5
      phenyltetrazole, an excited electron, which migrates from the phenyl ring to the
      tetrazole ring, induces bond cleavage catalytically. Using the MICD technique, we
      establish for the first time a link between the phenomenon of excited-state
      electron/charge transfer among aromatic rings and the intricate interplay of
      aromatic, antiaromatic and non-aromatic states.

PMID- 27711463
TI  - Fluorinated photopolymer waveguide thermo-optic switches with loss-compensation
      function based on erbium-containing cladding structure.
AB  - In this work, a novel polymer thermo-optic switch with loss compensation function
      is successfully designed and fabricated by direct UV-writing technology. The
      waveguide core and cladding layer material of the switch are based on the low
      loss fluorinated photopolymer and erbium-containing gain copolymer. The
      absorption loss characteristics and thermal stabilities of the core and cladding
      materials are studied. The optimal optical field distribution for loss
      compensation structures is analyzed by modifying refractive index difference
      between the core and cladding. The thermo-optic modulation effect of the optical
      signal transmission for the device is simulated. The insertion loss of the switch
      device is about 6 dB. The switching rise and fall time are 396.2 MUs and 461.2
      MUs applied by 500 Hz square-wave voltage, respectively. The switching power is
      6.5 mW, the extinction ratio of the switch is about 14 dB. The loss-compensation
      value of the entire chip is obtained as 1.9 dB at 1530 nm wavelength. The
      flexible loss-compensation multi-functional waveguide switch is appropriate for
      incorporation in large-scale opti-electronic integrated circuits.

PMID- 27711464
TI  - Photochemical CO2 reduction using structurally controlled g-C3N4.
AB  - Graphitic carbon nitride (g-C3N4) synthesised from a urea precursor is an
      excellent CO2 reduction photocatalyst using [Co(bpy)n]2+ as a co-catalyst. A five
      fold increase in activity for the highly polymerised urea derived g-C3N4 is
      achieved compared to alternative precursors. Transient absorption, time-resolved
      and steady-state emission studies indicate that the enhanced activity is related
      to both an increased driving force for photoelectron transfer and a greater
      availability of photogenerated charges.

PMID- 27711465
TI  - 35Cl dynamic nuclear polarization solid-state NMR of active pharmaceutical
      ingredients.
AB  - In this work, we show how to obtain efficient dynamic nuclear polarization (DNP)
      enhanced 35Cl solid-state NMR (SSNMR) spectra at 9.4 T and demonstrate how they
      can be used to characterize the molecular-level structure of hydrochloride salts
      of active pharmaceutical ingredients (APIs) in both bulk and low wt% API dosage
      forms. 35Cl SSNMR central-transition powder patterns of chloride ions are
      typically tens to hundreds of kHz in breadth, and most cannot be excited
      uniformly with high-power rectangular pulses or acquired under conditions of
      magic-angle spinning (MAS). Herein, we demonstrate the combination of DNP and 1H
      35Cl broadband adiabatic inversion cross polarization (BRAIN-CP) experiments for
      the acquisition of high quality wideline spectra of APIs under static sample
      conditions, and obtain signals up to 50 times greater than in spectra acquired
      without the use of DNP at 100 K. We report a new protocol, called spinning-on
      spinning-off (SOSO) acquisition, where MAS is applied during part of the
      polarization delay to increase the DNP enhancements and then the MAS rotation is
      stopped so that a wideline 35Cl NMR powder pattern free from the effects of
      spinning sidebands can be acquired under static conditions. This method provides
      an additional two-fold signal enhancement compared to DNP-enhanced SSNMR spectra
      acquired under purely static conditions. DNP-enhanced 35Cl experiments are used
      to characterize APIs in bulk and dosage forms with Cl contents as low as 0.45
      wt%. These results are compared to DNP-enhanced 1H-13C CP/MAS spectra of APIs in
      dosage forms, which are often hindered by interfering signals arising from the
      binders, fillers and other excipient materials.

PMID- 27711466
TI  - Deposition of ZnO on bismuth species towards a rechargeable Zn-based aqueous
      battery.
AB  - Zn aqueous batteries typically suffer from poor cycle life because water soluble
      zincate ions are formed during the oxidation of Zn. When Zn is oxidized, most of
      the Zn2+ ions detach from the current collector and become electrochemically
      inactive, leaving the battery non-rechargeable. Numerous reports demonstrate the
      use of Bi2O3 as an electrode additive to enhance electrochemical performance and
      they attribute this phenomenon to the improvement in electrical conductivity.
      However, conductivity does not have an effect on the intrinsic solubility of the
      zincate ion. We conduct a series of characterizations to provide a comprehensive
      mechanistic role of Bi2O3 in the Zn electrode. We find that upon oxidation,
      zincate ions are formed but they relax into ZnO on the surface of the bismuth
      species. This work proposes that the reason for the prolonged cycle life is due
      to the deposition of ZnO through relaxation and this prevents losing
      electrochemically active materials. This finding paves the way for further
      improving the cycle life and understanding the mechanism of the Zn based
      rechargeable aqueous batteries and possibly other conversion types of
      rechargeable batteries.

PMID- 27711467
TI  - Ice nucleation on nanotextured surfaces: the influence of surface fraction,
      pillar height and wetting states.
AB  - In this work, we address the nucleation behavior of a supercooled monatomic
      cylindrical water droplet on nanoscale textured surfaces using molecular dynamics
      simulations. The ice nucleation rate at 203 K on graphite based textured surfaces
      with nanoscale roughness is evaluated using the mean fast-passage time method.
      The simulation results show that the nucleation rate depends on the surface
      fraction as well as the wetting states. The nucleation rate enhances with
      increasing surface fraction for water in the Cassie-Baxter state, while contrary
      behavior is observed for the case of Wenzel state. Based on the spatial histogram
      distribution of ice formation, we observed two pathways for ice nucleation.
      Heterogeneous nucleation is observed at a high surface fraction. However, the
      probability of homogeneous ice nucleation events increases with decreasing
      surface fraction. We further investigate the role of the nanopillar height in ice
      nucleation. The nucleation rate is enhanced with increasing nanopillar height.
      This is attributed to the enhanced contact area with increasing nanopillar height
      and the shift in nucleation events towards the three-phase contact line
      associated with the nanotextured surface. The ice-surface work of adhesion for
      the Wenzel state is found to be 1-2 times higher than that in the Cassie-Baxter
      state. Furthermore, the work of adhesion of ice in the Wenzel state is found to
      be linearly dependent on the contour length of the droplet, which is in line with
      that reported for liquid droplets.

PMID- 27711468
TI  - Construction of gyroid-structured matrices through the design of geminized
      amphiphilic zwitterions and their self-organization.
AB  - Gemini amphiphilic zwitterions exhibit thermotropic bicontinuous cubic liquid
      crystalline phases having a 3D continuous ionic domain. Incorporation of an acid
      into the materials led to the creation of novel electrolytes transporting protons
      efficiently through the 3D continuous domain.

PMID- 27711469
TI  - Influence of counterions on the conformation of conjugated polyelectrolytes: the
      case of poly(thiophen-3-ylacetic acid).
AB  - The addition of simple salt to a solution of conjugated polyelectrolyte can lead
      to substantial changes in its optical properties caused by the conformational
      change of the polymer chain. The effect of the addition of alkali metal and
      tetraalkylammonium chlorides to solutions of lithium salt of poly(thiophen-3
      ylacetic acid) is investigated by NMR. The fractions of free alkali metal
      counterions are in agreement with predictions of the cylindrical Poisson
      Boltzmann cell model. On the other hand, the fractions of free tetraalkylammonium
      counterions deviate from the prediction of this model and diminish with
      increasing size of these counterions. This trend is consistent with observed
      ultraviolet-visible absorption spectra and measured self-diffusion coefficients
      of the polyion in mixtures with tetraalkylammonium salts. A transition to more
      constricted conformation of the polyion chain becomes more pronounced with the
      lengthening of alkyl groups in the added tetraalkylammonium cation. Taking into
      account the obtained fractions of free counterions, existing thermodynamic data
      are reanalysed in order to determine thermodynamic parameters for binding of
      different counterions to the polyion. This analysis shows that standard
      enthalpies of binding of alkali metal counterions are distinctively different,
      which is most probably related to differences in hydration shells of counterions.
      On the other hand, such an analysis fails in the case of tetraalkylammonium
      chlorides where obviously more complex changes take place.

PMID- 27711470
TI  - Catalytic effects of silver plasmonic nanoparticles on the redox reaction leading
      to ABTS+ formation studied using UV-visible and Raman spectroscopy.
AB  - ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) is a compound
      extensively employed to evaluate the free radical trapping capacity of
      antioxidant agents and complex mixtures such as biological fluids or foods. This
      evaluation is usually performed by using a colourimetric experiment, where
      preformed ABTS radical cation (ABTS+) molecules are reduced in the presence of an
      antioxidant causing an intensity decrease of the specific ABTS+ UV-visible
      absorption bands. In this work we report a strong effect of silver plasmonic
      nanoparticles (Ag NPs) on ABTS leading to the formation of ABTS+. The reaction of
      ABTS with Ag NPs has been found to be dependent on the interfacial and plasmonic
      properties of NPs. Specifically, this reaction is pronounced in the presence of
      spherical nanoparticles prepared by the reduction of silver nitrate with
      hydroxylamine (AgH) and in the case of star-shaped silver nanoparticles (AgNS).
      On the other hand, spherical nanoparticles prepared by the reduction of silver
      nitrate with citrate apparently do not react with ABTS. Additionally, the
      formation of ABTS+ is investigated by surface-enhanced Raman scattering (SERS)
      and the assignment of the most intense vibrational bands of this compound is
      performed. The SERS technique enables us to detect this radical cation at very
      low concentrations of ABTS (~2 MUM). Altogether, these findings allow us to
      suggest the use of ABTS/Ag NPs-systems as reliable and easy going substrates to
      test the antioxidant capacity of various compounds, even at concentrations much
      lower than those usually used in the spectrophotometric assays. Moreover, we have
      suggested that ABTS could be employed as a suitable agent to investigate the
      interfacial and plasmonic properties of the metal nanoparticles and, thus, to
      characterize the nanoparticle metal systems employed for various purposes.

PMID- 27711471
TI  - The influence of solution environment on the nucleation kinetics and
      crystallisability of para-aminobenzoic acid.
AB  - The influence of solvent type on the solution thermodynamics, nucleation-kinetics
      and crystal growth of alpha para-aminobenzoic acid (PABA) crystallising from
      supersaturated ethanol, acetonitrile and water solutions, is examined using poly
      thermal analysis of the metastable zone width. Application of a recently proposed
      model for analysis of crystallisation kinetics (J. Cryst. Growth, 2010, 312, 698
      704) indicates a solvent and concentration dependence of the nucleation mechanism
      and key nucleation parameters for the alpha form of PABA. The mechanism of
      nucleation is found to change from instantaneous to progressive with decreasing
      concentration and also when changing the solvent from ethanol to acetonitrile to
      water. The dependence of the nucleation mechanism is correlated to the kinetic
      component of the nucleation rate through calculated values of instantaneously
      nucleated crystallites, which increase from 1.40 * 109 m-3 in ethanol to 1.08 *
      1010 m-3 in acetonitrile to 2.58 * 1010 m-3 in water. This in combination with
      low calculated number concentrations of interfacial tension between 1.13 and 2.71
      mJ m-2, supports the conclusion that the kinetic component of the nucleation rate
      is more limiting when crystallising PABA from ethanol solutions in comparison to
      water solutions. This finding is further supported by molecular dynamics
      simulations of the solvation free energy of PABA, which is found to be greatest
      in water, -42.4 kJ mol-1 and lowest in ethanol, -58.5 kJ mol-1.

PMID- 27711472
TI  - Chemodivergent synthesis of multi-substituted/fused pyrroles via copper-catalyzed
      carbene cascade reaction of propargyl alpha-iminodiazoacetates.
AB  - A novel cascade reaction of alkynyl-tethered alpha-iminodiazoacetates has been
      developed, which provides a general access to both multi-substituted and fused
      pyrroles in high yields with a broad substrate scope. The gamma-imino carbene is
      proposed as the key intermediate in this divergent reaction and followed by
      unpresented transformations.

PMID- 27711473
TI  - Excited-state intramolecular proton transfer and conformational relaxation in 4'
      N,N-dimethylamino-3-hydroxyflavone doped in acetonitrile crystals.
AB  - The effect of intermolecular interactions on excited-state intramolecular proton
      transfer (ESIPT) in 4'-N,N-dimethylamino-3-hydroxyflavone (DMHF) doped in
      acetonitrile crystals was investigated by measuring its temperature dependence of
      steady-state fluorescence excitation and fluorescence spectra and picosecond time
      resolved spectra. The relative intensity of emission from the excited state of
      the normal form (N*) to that from the excited state of the tautomer form (T*) and
      spectral features changed markedly with temperature. Unusual changes in the
      spectral shift and spectral features were observed in the fluorescence spectra
      measured between 200 and 218 K, indicating that a solid-solid phase transition of
      DMHF-doped acetonitrile crystals occurred. Time-resolved fluorescence spectra
      suggested conformational relaxation of the N* state competed with ESIPT after
      photoexcitation and the ESIPT rate increased with temperature in the low
      temperature phase of acetonitrile. However, the intermolecular interaction of N*
      with acetonitrile in the high-temperature phase markedly stabilized the potential
      minimum of the fluorescent N* state and slowed the ESIPT. This stabilization can
      be explained by reorganization of acetonitrile originating from the strong
      electric dipole-dipole interaction between DMHF and acetonitrile molecules.

PMID- 27711474
TI  - Conformation controlled turn on-turn off phosphorescence in a metal-free
      biluminophore: thriving the paradox that exists for organic compounds.
AB  - The legacy of phosphorescence from expensive organometallic compounds has
      inspired researchers to develop efficient metal-free organic phosphors. Although
      organic phosphors offer a cheaper alternative, the long-lived triplets of organic
      phosphors that are primarily consumed by vibrational dissipation need to be
      adequately suppressed, and this provides an opportunity to design new organic
      entities, at par with the organometallic compounds, based on conformational
      control and incorporation of useful functional groups to alter their emissive
      properties, especially phosphorescence. Here, we have achieved a proficient dual
      state emission, underlining the key design rule of conformational control in an
      organic molecular platform for 2-(6-chlorobenzo[d]thiazol-2-yl)-1H
      benzo[de]isoquinoline-1,3(2H)-dione (CBIQD). In contrast to other known
      naphthalimides, the system limiting access to non-radiative triplet states is
      achieved by steric encumbrance which exhibits strong phosphorescence. Here, in
      addition to strong fluorescence (from planar conformer), phosphorescence is
      unlocked by suppression of non-radiative channels from the non-planar conformer
      in glassy solvents (77 K) and when embedded in a polymer matrix of poly(methyl
      methacrylate) (PMMA) at RT. The spectroscopic delineation of adopted geometry and
      optical property relationship is sought by a steric approach, extent of
      intramolecular charge transfer (ICT), presence of carbonyl groups, directed heavy
      atom effect and the spin-orbit coupling (SOC) invoked by -S- and -Cl atoms. Time
      dependent density functional theory (TD-DFT) is used to explain the favourable
      mechanistic path for the decay of excited states (ESs) leading to phosphorescence
      from a non-planar conformer and fluorescence from a planar conformer. The
      spectacular access to the radiative singlet and triplet states suggests that
      there is less scope for loss channels. The phosphorescence of the CBIQD-PMMA
      system may find use in other biomedical applications due to the biocompatibility
      of each component.

PMID- 27711475
TI  - The use of reduced copper metal-organic frameworks to facilitate CuAAC click
      chemistry.
AB  - A reduced copper metal-organic framework (rCu-MOF) containing CuI ions was
      prepared by reducing raw MOFs (Cu-BTC). A series of polymer functionalizations
      and coupling reactions could subsequently be achieved via CuAAC click chemistry,
      thus demonstrating the high activity, facile recyclability and good structural
      stability of rCu-MOFs for catalytic applications.

PMID- 27711476
TI  - Role of ion hydration for the differential capacitance of an electric double
      layer.
AB  - The influence of soft, hydration-mediated ion-ion and ion-surface interactions on
      the differential capacitance of an electric double layer is investigated using
      Monte Carlo simulations and compared to various mean-field models. We focus on a
      planar electrode surface at physiological concentration of monovalent ions in a
      uniform dielectric background. Hydration-mediated interactions are modeled on the
      basis of Yukawa potentials that add to the Coulomb and excluded volume
      interactions between ions. We present a mean-field model that includes hydration
      mediated anion-anion, anion-cation, and cation-cation interactions of arbitrary
      strengths. In addition, finite ion sizes are accounted for through excluded
      volume interactions, described either on the basis of the Carnahan-Starling
      equation of state or using a lattice gas model. Both our Monte Carlo simulations
      and mean-field approaches predict a characteristic double-peak (the so-called
      camel shape) of the differential capacitance; its decrease reflects the packing
      of the counterions near the electrode surface. The presence of hydration-mediated
      ion-surface repulsion causes a thin charge-depleted region close to the surface,
      which is reminiscent of a Stern layer. We analyze the interplay between excluded
      volume and hydration-mediated interactions on the differential capacitance and
      demonstrate that for small surface charge density our mean-field model based on
      the Carnahan-Starling equation is able to capture the Monte Carlo simulation
      results. In contrast, for large surface charge density the mean-field approach
      based on the lattice gas model is preferable.

PMID- 27711477
TI  - Tuning the electronic and magnetic properties of graphene-like SiGe hybrid
      nanosheets by surface functionalization.
AB  - In this paper, the structural, electronic and magnetic properties of fully and
      partially surface modified SiGe nanosheets (NSs) have been investigated using
      first-principles calculations based on density functional theory. The results
      demonstrate that the electronic and magnetic properties of SiGe NSs can be tuned
      by decorating H, Cl and F atoms on Si sites in SiGe NSs. It is shown that by
      decorating their surface with H, F, and Cl atoms, H-SiGe, F-SiGe, and Cl-SiGe NSs
      in FM states are predicted to behave as a semiconductor, half-metal, and metal,
      respectively. The diverse electronic and magnetic properties define the potential
      applications of SiGe nanosheets in electronics and spintronics.

PMID- 27711478
TI  - Observation of a new channel, the production of CH3, in the abstraction reaction
      of OH radicals with acetaldehyde.
AB  - Using laser flash photolysis coupled to photo-ionization time-of-flight mass
      spectrometry (PIMS), methyl radicals (CH3) have been detected as primary products
      from the reaction of OH radicals with acetaldehyde (ethanal, CH3CHO) with a yield
      of ~15% at 1-2 Torr of helium bath gas. Supporting measurements based on laser
      induced fluorescence studies of OH recycling in the OH/CH3CHO/O2 system are
      consistent with the PIMS study. Master equation calculations suggest that the
      origin of the methyl radicals is from prompt dissociation of chemically activated
      acetyl products and hence is consistent with previous studies which have shown
      that abstraction, rather than addition/elimination, is the sole route for the OH
      + acetaldehyde reaction. However, the observation of a significant methyl product
      yield suggests that energy partitioning in the reaction is different from the
      typical early barrier mechanism where reaction exothermicity is channeled
      preferentially into the newly formed bond. The master equation calculations
      predict atmospheric yields of methyl radicals of ~9%. The implications of the
      observations in atmospheric and combustion chemistry are briefly discussed.

PMID- 27711479
TI  - Redox tunable delivery systems: sweet block copolymer micelles via thiol
      (bromo)maleimide conjugation.
AB  - Oligosaccharide-based block copolymers (OBCPs) are synthesized by thiol click
      conjugation using reducing-end thiol-containing xyloglucooligosaccharides and
      maleimide- or bromomaleimide-terminated polycaprolactone. The self-assembled
      OBCPs in aqueous solution lead to redox-sensitive micelles with different
      responsiveness. This distinguishing feature allows us to control the release of
      entrapped hydrophobic Nile red by mixing both OBCPs.

PMID- 27711480
TI  - Benchmark values of chemical potential and chemical hardness for atoms and atomic
      ions (including unstable anions) from the energies of isoelectronic series.
AB  - We present benchmark values for the electronic chemical potential and chemical
      hardness from reference data for ionization potentials and electron affinities.
      In cases where the energies needed to compute these quantities are not available,
      we estimate the ionization potential of the metastable (di)anions by
      extrapolation along the isoelectronic series, taking care to ensure that the
      extrapolated data satisfy reasonable intuitive rules to the maximum possible
      extent. We also propose suitable values for the chemical potential and chemical
      hardness of zero-electron species. Because the values we report are faithful to
      the trends in accurate data on atomic energies, we believe that our proposed
      values for the chemical potential and chemical hardness are ideally suited to
      conceptual studies of chemical trends across the periodic table. The critical
      nuclear charge (Z critical) of the isoelectronic series with 2 < N < 96 has also
      been reported for the first time.

PMID- 27711481
TI  - Theoretical and experimental investigation on structural, electronic and magnetic
      properties of layered Mn5O8.
AB  - We have investigated the crystal, electronic, and magnetic structures of Mn5O8 by
      means of state-of-the-art density functional theory calculations and neutron
      powder diffraction (NPD) measurements. This compound stabilizes in the monoclinic
      structure with space group C2/m where the Mn ions are in the distorted octahedral
      and trigonal prismatic coordinations with oxygen atoms. The calculated structural
      parameters based on total energy calculations are found to be in excellent
      agreement with low temperature NPD measurements when we accounted for the correct
      magnetic structure and Coulomb correlation effect in the computation. Using fully
      relativistic generalized-gradient approximation with Hubbard U (GGA+U) we found
      that the magnetic ordering in Mn5O8 is A-type antiferromagnetic and the direction
      of the easy axis is [1 0 0] in agreement with susceptibility and NPD
      measurements. However, the calculation without the inclusion of Hubbard U leads
      to ferrimagnetic half metal as a ground state contradictory to experimental
      findings, indicating the presence of a strong Coulomb correlation effect in this
      material. The GGA calculation without the Coulomb correction effect itself is
      sufficient to reproduce the experimentally observed magnetic moments in various
      Mn sites. We found that Mn in this material exhibits mixed valence behavior with
      2+ and 4+ oxidation states reflecting different magnetic moments in the Mn sites.
      We explored the electronic band characteristics using total, site-, and orbital
      projected density of states which emphasized the mixed-valent nature of Mn. A
      dominant Mn 3d character of the density of states at Fermi energy is the origin
      for the metallic behavior of Mn5O8. The bond strength analysis based on the
      crystal orbital Hamiltonian population between constituents indicates strong
      anisotropy in the bonding behavior which results from the layered nature of its
      crystal structure. Our bonding analysis shows that there is a noticeable covalent
      bond between Mn 3d-O 2p states which stabilizes the observed low symmetric
      structure. Our experimental findings and theoretical predictions suggest that
      Mn5O8 can be classified as a strongly correlated mixed valent antiferromagnetic
      metal.

PMID- 27711482
TI  - Photocatalytic oxidation of methane over SrCO3 decorated SrTiO3 nanocatalysts via
      a synergistic effect.
AB  - Because of the high C-H bond energy as well as the non-polar feature of CH4
      molecules, oxidation of methane under mild conditions remains a challenging task
      for both C1 utilization and atmospheric environmental cleansing. Here we report
      that by using a sol-gel method SrCO3 decorated SrTiO3 nanocatalysts (SrTiO3-S)
      with an average particle size of ~25 nm can be readily prepared, which
      surprisingly show efficient performance for photocatalytic oxidation of methane
      with the activity close to fourfold of P25, a benchmark photocatalyst. Further
      investigation revealed a synergistic effect between SrCO3 and SrTiO3 when
      combined together into a composite material as both of which are totally inactive
      for methane oxidation if used alone. Gas adsorption characterization disclosed
      that the SrCO3 can adsorb methane and cannot adsorb carbon dioxide, whereas the
      SrTiO3 will preferentially adsorb CO2 instead of CH4. Photocurrent and
      photoluminescence measurements indicate that SrCO3 exhibits a negligible
      photocurrent response relative to the SrTiO3 semiconductor under simulated solar
      light illumination but the formation of the SrCO3/SrTiO3 junction structure
      (SrTiO3-S) helps reduce surface recombination of the photogenerated electrons and
      holes. All these results refer to the synergistic mechanism in which the SrCO3
      acts as a trapping agent to adsorb methane and weaken its C-H bond while the
      SrTiO3 acts as a photocatalyst to activate and oxidize methane under light
      illumination. The underlying photooxidation mechanism is further investigated
      with the aid of in situ electron paramagnetic resonance and infrared
      spectroscopy.

PMID- 27711483
TI  - Electronic and optical properties of MAPbX3 perovskites (X = I, Br, Cl): a
      unified DFT and GW theoretical analysis.
AB  - Materials engineering is a key for the enhancement of photovoltaics technology.
      This is particularly true for the novel class of perovskite solar cells. Accurate
      theoretical modelling can help establish general trends of behavior when
      addressing structural changes. Here, we consider the effects due to halide
      substitution in organohalide CH3NH3PbX3 perovskites exploring the halide series
      with X = Cl, Br, I. For this task, we use accurate DFT and GW methods including
      spin-orbit coupling. We find the expected band gap increase when moving from X =
      I to Cl, in line with the experimental data. Most notably, the calculated
      absorption coefficients for I, Br and Cl are nicely reproducing the behavior
      reported experimentally. A common feature of all the simulated band structures is
      a significant Rashba effect. This is similar for MAPbI3 and MAPbBr3 while MAPbCl3
      shows in general a reduced Rashba interaction coefficient. Finally, a monotonic
      increase of the exciton reduced masses is calculated when moving from I to Br to
      Cl, in line with the stronger excitonic character of the lighter perovskite
      halides.

PMID- 27711484
TI  - Thermodynamics and kinetics of carbon deposits on cobalt: a combined density
      functional theory and kinetic Monte Carlo study.
AB  - We have built a lattice gas model for cobalt-carbon interaction to investigate
      the thermodynamics and kinetics of carbon deposition on Co(0001) surfaces. The
      formation of carbon structures on cobalt is considered to be one of the causes of
      deactivation of a cobalt Fischer-Tropsch (FT) catalyst. The formation of graphene
      - the most thermodynamically stable phase under FT conditions - is kinetically
      inhibited during the first 30 hours of exposure of the surface to carbon, while
      the build-up of surface carbide is the fastest reaction. Our simulations clearly
      show that the kinetics of carbon deposition is the result of two competing
      effects: a fast subsurface diffusion and a slower surface diffusion to form a
      carbon-carbon bond.

PMID- 27711485
TI  - Label-free ratiometric electrochemical detection of the mutated apolipoprotein E
      gene associated with Alzheimer's disease.
AB  - A novel ratiometric electrochemical nanosensing platform was developed based on
      graphene and mesoporous hybrid nanomaterials for detection of the mutated
      apolipoprotein E gene associated with Alzheimer's disease. The introduction of
      ratiometric assay could cancel out some systematic errors and significantly
      improved the sensing performance, such as reproducibility, reliability and
      accuracy.

PMID- 27711486
TI  - Atomistic insights into deep eutectic electrolytes: the influence of urea on the
      electrolyte salt LiTFSI in view of electrochemical applications.
AB  - The influence of urea on the conducting salt lithium bis
      (trifluoromethanesulfonyl)-imide (LiTFSI) in terms of lithium ion coordination
      numbers and lithium ion transport properties is studied via atomistic molecular
      dynamics simulations. Our results indicate that the presence of urea favors the
      formation of a deep eutectic electrolyte with pronounced ion conductivities which
      can be explained by a competition between urea and TFSI in occupying the first
      coordination shell around lithium ions. All simulation findings verify that high
      urea concentrations lead to a significant increase of ionic diffusivities and an
      occurrence of relatively high lithium transference numbers in good agreement with
      experimental results. The outcomes of our study point at the possible application
      of deep eutectic electrolytes as ion conducting materials in lithium ion
      batteries.

PMID- 27711487
TI  - Metallic nanowires and mesoscopic networks on a free surface of superfluid helium
      and charge-shuttling across the liquid-gas interface.
AB  - We investigate the motion of electrically charged metallic nano- and
      microparticles produced by laser ablation in He gas and injected into superfluid
      helium. In the presence of a vertical static electric field, the particles either
      perform a repetitive shuttle-like motion transporting the charge across the
      liquid-gas interface or become trapped under the free surface of liquid He and
      coalesce into long filaments and complex two-dimensional mesoscopic networks. A
      classical electrohydrodynamic model is used to describe the motion of charged
      microparticles in superfluid He. The resulting filaments and networks are
      analyzed using electron microscopy. It is demonstrated that each filament is in
      fact composed of a large number of nanowires with a characteristic diameter of
      order of 10 nm and extremely large aspect ratios.

PMID- 27711488
TI  - Observation of nanotwinning and room temperature ferromagnetism in sub-5 nm
      BiFeO3 nanoparticles: a combined experimental and theoretical study.
AB  - Particle size significantly affects the properties and therefore the potential
      applications of multiferroics. However, is there special particle size effect in
      BiFeO3, which has a spiral modulated spin structure? This is still under
      investigation for sub-5 nm BiFeO3. In this report, the structural, electronic and
      magnetic properties are investigated for chemically synthesized BiFeO3
      nanoparticles with an average size of 3 nm. We observed nanotwinning features in
      the specific size regime of the nanoparticles (2-4 nm). A weak Bi-O-Fe
      coordination and weak covalent nature has been observed in the nanoparticles
      through high-resolution electron energy loss spectroscopy and theoretical
      analysis, confirming that BiFeO3 nanoparticles a retain rudimentary R3c phase
      even at sub-5 nm dimensions. The R3c phase of sub-5 nm BiFeO3 nanoparticles has
      also been confirmed using Raman spectroscopy and Raman mapping of the vibrational
      modes. The nanoparticles display cluster spin glass, room temperature
      ferromagnetism, and a metamictization-davidite phase. The observation of weak
      magnetic entropy features confirmed the presence of a weak correlation between
      the magnetic and ferroelectric components. To support our experimental
      observations, we have simulated a sub-5 nm BiFeO3 nanocluster. Using density
      functional theory, the ferromagnetic ground state and the presence of a weak
      covalent nature in the nanocluster is established considering the first Brillouin
      zone, thus confirming our experimental results. Finding of new physicochemical
      features in sub-5 nm BiFeO3 would be beneficial for the understanding of the
      fundamental physical and chemical science as well as potential device
      development.

PMID- 27711489
TI  - Gate-tunable diode-like current rectification and ambipolar transport in
      multilayer van der Waals ReSe2/WS2 p-n heterojunctions.
AB  - Vertically stacked van der Waals (vdW) heterojunctions of two-dimensional (2D)
      transition metal dichalcogenides (TMDs) have attracted a great deal of attention
      due to their fascinating properties. In this work, we report two important gate
      tunable phenomena in new artificial vdW p-n heterojunctions created by vertically
      stacking p-type multilayer ReSe2 and n-type multilayer WS2: (1) well-defined
      strong gate-tunable diode-like current rectification across the p-n interface is
      observed, and the tunability of the electronic processes is attributed to the
      tunneling-assisted interlayer recombination induced by majority carriers across
      the vdW interface; (2) the distinct ambipolar behavior under gate voltage
      modulation both at forward and reverse bias voltages is found in the vdW
      ReSe2/WS2 heterojunction transistors and a corresponding transport model is
      proposed for the tunable polarity behaviors. The findings may provide some new
      opportunities for building nanoscale electronic and optoelectronic devices.

PMID- 27711490
TI  - Calcium-decorated carbon nanostructures for the selective capture of carbon
      dioxide.
AB  - The development of advanced materials for CO2 capture is of great importance for
      mitigating climate change. In this paper, we outline our discovery that calcium
      decorated carbon nanostructures, i.e., zigzag graphene nanoribbons (ZGNRs),
      carbyne, and graphyne, have great potential for selective CO2 capture, as
      demonstrated via first-principles calculations. Our findings show that Ca
      decorated ZGNRs can bind up to three CO2 molecules at each Ca atom site with an
      adsorption energy of ~-0.8 eV per CO2, making them suitable for reversible CO2
      capture. They adsorb CO2 molecules preferentially, compared with other gas
      molecules such as H2, N2, and CH4. Moreover, based on equilibrium thermodynamical
      simulations, we confirm that Ca-decorated ZGNRs can capture CO2 selectively from
      a gas mixture with a capacity of ~4.5 mmol g-1 under ambient conditions. Similar
      results have been found in other carbon nanomaterials, indicating the generality
      of carbon based nanostructures for selective CO2 capture under ambient
      conditions.

PMID- 27711491
TI  - Ritter-type amination of C-H bonds at tertiary carbon centers using iodic acid as
      an oxidant.
AB  - The Ritter-type amination of a tertiary C-H bond using iodic acid (HIO3) as an
      oxidant, in the presence of N-hydroxyphthalimide (NHPI) is reported. This
      operationally simple method is conducted under metal-free conditions, is
      scalable, and efficiently provides valuable alpha-tertiary amine derivatives.

PMID- 27711492
TI  - One-step assembly of a hierarchically porous phenolic resin-type polymer with
      high stability for CO2 capture and conversion.
AB  - A hierarchically porous phenolic resin-type polymer has been successfully
      prepared by a solvothermal reaction. Given the relatively high surface area,
      hierarchical pores, good stability and abundant -OH reactive groups, this polymer
      exhibits high CO2 adsorption and efficient catalytic conversion for CO2
      cycloaddition.

PMID- 27711493
TI  - Raman excess spectroscopy vs. principal component analysis: probing the
      intermolecular interactions between chiral molecules and imidazolium-based ionic
      liquids.
AB  - Raman spectroscopy is a very sensitive and specific measurement tool for probing
      intermolecular interaction structures. As imidazolium-based ionic liquids can
      favorably be used for enantioseparation, in this work two approaches for Raman
      signal analysis, namely by means of excess spectra and principal component
      analysis (PCA), are compared to extract detailed information about the
      interaction structure of the enantiomers d- and l-glucose in an aqueous solution
      of the ionic liquid [EMIM][EtSO4]. In contrast to the excess calculations, the
      loadings obtained from PCA lead to significant results since the interactions are
      weighted by their strength and significance. Moreover, the analysis of the
      weighted vibrations in the loadings indicate that hydrogen bonds are particularly
      formed between the ethyl sulphate anion of [EMIM][EtSO4] and the hydrogen atom of
      the OH-group at the C6-atom of glucose.

PMID- 27711494
TI  - Outstanding surface plasmon resonance performance enabled by templated oxide
      gratings.
AB  - Here we report a simple and scalable soft-lithography-based templating technology
      for fabricating Au-covered oxide (titania and zirconia) gratings by using DVDs as
      a structural template. The resulting plasmonic gratings simultaneously exhibit
      very high surface plasmon resonance (SPR) sensitivity (up to ~940 nm per
      refractive index unit, nm per RIU) and figure of merit (FOM, up to 62.5). The
      effects of thermal annealing of the templated oxide gratings on their final
      plasmonic properties have been systematically investigated by both experiments
      and finite-difference time-domain (FDTD) simulations. Higher SPR sensitivities
      and slightly reduced FOMs have been observed for the annealed gratings.
      Additionally, the amplitude of the SPR dips gradually decreases with increasing
      annealing temperatures. Scanning electron microscopy and X-ray diffraction show
      that the annealing process enlarges the crystal domain sizes of the oxides and
      smoothens the final plasmonic grating surface. Systematic FDTD simulations reveal
      that the SPR properties (e.g., dip amplitude) of Au-covered oxide gratings are
      significantly affected by the deformation of the track-pitch structure caused by
      thermal annealing, agreeing with the experimental results. The outstanding SPR
      performance combined with the high thermal stability of the crystalline oxides
      could make the templated plasmonic gratings a promising SPR platform for many
      important sensing applications, such as in situ probing heterogeneous catalytic
      reactions under realistic conditions.

PMID- 27711495
TI  - Variational first hyperpolarizabilities of 2,3-naphtho-15-crown-5 ether
      derivatives with cation-complexing: a potential and selective cation detector.
AB  - Crown ethers, as a kind of heterocycle, have been the subject of great interest
      over recent decades due to their selective capability to bind to metal cations.
      The use of a constant crown ether, such as naphtho-15-crown-5 (N15C5), and varied
      metal cations (Li+, Na+, K+, Be2+, Mg2+, Ca2+, Co2+, Ni2+, Cu2+) makes it
      possible to determine the contributions of the metal cations to nonlinear optical
      (NLO) responses and to design an appropriate NLO-based cation detector. N15C5 and
      its metal cation derivatives have been systematically investigated by density
      functional theory. It is found that the dependency of the first
      hyperpolarizability relies on the metal cation, especially for transition metals.
      The decrease of the first hyperpolarizabilities for alkali metal cation
      derivatives is due to their relatively low oscillator strengths, whereas the
      significant increase of the first hyperpolarizabilities for transition metal
      cation derivatives can be further illustrated by their low transition energies,
      large amplitudes and separate distributions of first hyperpolarizability density.
      Thus, the alkali metal and transition metal cations are distinguishable and the
      transition metal cations are easier to detect by utilizing the variations in NLO
      responses.

PMID- 27711496
TI  - A facile strategy for accessing 3-alkynylchromones through gold-catalyzed
      alkynylation/cyclization of o-hydroxyarylenaminones.
AB  - A strategy based on tandem alkynylation of o-hydroxyarylenaminones followed by
      intramolecular cyclization has been developed to generate a diverse array of 3
      alkynyl chromones. The functionality embedded in these key intermediates enables
      their facile elaboration into more diverse structures by a variety of
      functionalizations and ring-forming processes.

PMID- 27711497
TI  - Induction of unidirectional pi-electron rotations in low-symmetry aromatic ring
      molecules using two linearly polarized stationary lasers.
AB  - A new laser-control scenario of unidirectional pi-electron rotations in a low
      symmetry aromatic ring molecule having no degenerate excited states is proposed.
      This scenario is based on dynamic Stark shifts of two relevant excited states
      using two linearly polarized stationary lasers. Each laser is set to selectively
      interact with one of the two electronic states, the lower and higher excited
      states are shifted up and down with the same rate, respectively, and the two
      excited states become degenerate at their midpoint. One of the four control
      parameters of the two lasers, i.e. two frequencies and two intensities,
      determines the values of all the other parameters. The direction of pi-electron
      rotations, clockwise or counter-clockwise rotation, depends on the sign of the
      relative phase of the two lasers at the initial time. An analytical expression
      for the time-dependent expectation value of the rotational angular momentum
      operator is derived using the rotating wave approximation (RWA). The control
      scenario depends on the initial condition of the electronic states. The control
      scenario with the ground state as the initial condition was applied to toluene
      molecules. The derived time-dependent angular momentum consists of a train of
      unidirectional angular momentum pulses. The validity of the RWA was checked by
      numerically solving the time-dependent Schrodinger equation. The simulation
      results suggest an experimental realization of the induction of unidirectional pi
      electron rotations in low-symmetry aromatic ring molecules without using any
      intricate quantum-optimal control procedure. This may open up an effective
      generation method of ring currents and current-induced magnetic fields in
      biomolecules such as amino acids having aromatic ring molecules for searching
      their interactions.

PMID- 27711498
TI  - Exploration of the phase diagram of liquid water in the low-temperature
      metastable region using synthetic fluid inclusions.
AB  - We present new experimental data of the low-temperature metastable region of
      liquid water derived from high-density synthetic fluid inclusions (996-916 kg m
      3) in quartz. Microthermometric measurements include: (i) prograde (upon heating)
      and retrograde (upon cooling) liquid-vapour homogenisation. We used single
      ultrashort laser pulses to stimulate vapour bubble nucleation in initially
      monophase liquid inclusions. Water densities were calculated based on prograde
      homogenisation temperatures using the IAPWS-95 formulation. We found retrograde
      liquid-vapour homogenisation temperatures in excellent agreement with IAPWS-95.
      (ii) Retrograde ice nucleation. Raman spectroscopy was used to determine the
      nucleation of ice in the absence of the vapour bubble. Our ice nucleation data in
      the doubly metastable region are inconsistent with the low-temperature trend of
      the spinodal predicted by IAPWS-95, as liquid water with a density of 921 kg m-3
      remains in a homogeneous state during cooling down to a temperature of -30.5 
      degrees C, where it is transformed into ice whose density corresponds to zero
      pressure. (iii) Ice melting. Ice melting temperatures of up to 6.8  degrees C
      were measured in the absence of the vapour bubble, i.e. in the negative pressure
      region. (iv) Spontaneous retrograde and, for the first time, prograde vapour
      bubble nucleation. Prograde bubble nucleation occurred upon heating at
      temperatures above ice melting. The occurrence of prograde and retrograde vapour
      bubble nucleation in the same inclusions indicates a maximum of the bubble
      nucleation curve in the rho-T plane at around 40  degrees C. The new experimental
      data represent valuable benchmarks to evaluate and further improve theoretical
      models describing the p-V-T properties of metastable water in the low-temperature
      region.

PMID- 27711500
TI  - Enantioselective formation of cyclopropane spiroindenes from benzofulvenes by
      phase transfer catalysis.
AB  - The enantio- and diastereoselective formation of indenes spirofused to highly
      substituted cyclopropanes is described. The application of a new cinchona
      alkaloid derived ammonium salt in a phase transfer catalysis setup facilitates
      high selectivity and excellent yields at low catalyst loadings (0.1-1.0 mol%).

PMID- 27711499
TI  - The 3D [(Cu2Br2){MU-EtS(CH2)4SEt}]n material: a rare example of a coordination
      polymer exhibiting triplet-triplet annihilation.
AB  - EtS(CH2)4SEt, L1, forms with CuI a luminescent 2D polymer [Cu4I4{MU-L1}2]n (CP1),
      which exhibits no triplet excitation energy migration, but with CuBr, it forms a
      3D material (CP2), [(Cu2Br2){MU-L1}]n consisting of parallel (Cu2Br2S2)n layers
      bridged by L1's. CP2 shows T1-T1 annihilation at 298 K but not at 77 K.

PMID- 27711501
TI  - First exploration of freestanding and flexible Na2+2xFe2-x(SO4)3@porous carbon
      nanofiber hybrid films with superior sodium intercalation for sodium ion
      batteries.
AB  - The design of a freestanding electrode is the key to the development of energy
      storage devices with superior electrochemical performance and mechanical
      durability. Herein, we propose a highly-scalable strategy for the facile
      synthesis of a freestanding alluaudite Na2+2xFe2-x(SO4)3@porous carbon-nanofiber
      hybrid film, which is used as a self-supported and flexible electrode for sodium
      ion batteries. By the combined use of electrospinning and electrospraying, the
      freestanding hybrid film is constructed in the form of sulfate nanoparticles
      enwrapped in highly porous graphitic-like carbon-nanofibers. The multimodal
      porous architecture of the freestanding hybrid film ensures its superiority in
      mechanical flexibility and structural stability during repeated electrochemical
      processes, which meets the long-standing challenge of practical application.
      Moreover, both the highly conductive and porous framework and the nanoscale
      particles are favorable for promoting fast electron/ion transport capability.
      Compared with other carbon based supports such as graphene (GA), carbon nanotubes
      (CNTs) and active carbons (ACs), the flexible carbon nanofiber shows better
      interaction with electrochemical active materials and superior electrochemical
      properties. It retains over 95% of the capacity after five hundred cycles at
      alternate rates of 40C and 5C, which demonstrates the superior ultralong time and
      high-rate cycling capability. Therefore, the present work provides a facile and
      highly scalable strategy for the design and fabrication of high-performance
      freestanding sulfate cathodes for advanced sodium ion batteries.

PMID- 27711502
TI  - Isomerization of the methoxy radical revisited: the impact of water dimers.
AB  - Investigations carried out at MP2 and CCSD(T) levels of theory show that water
      dimers can compete with formic and sulfuric acids in catalyzing the isomerization
      of methoxy radicals in the lower troposphere. The rate coefficients for water
      catalyzed reactions showed opposite temperature dependence to that of acid
      catalyzed reactions and they were found to play an important role in determining
      the relative impacts of these catalysts under different atmospheric conditions.

PMID- 27711503
TI  - Ab initio study of hydrogen chemisorption in nitrogen-doped carbon nanotubes.
AB  - The electronic structure of single walled nitrogen-doped carbon nanotubes is
      calculated by first principles using density functional theory within the
      supercell approach with periodic boundary conditions. The effect of the
      adsorption of hydrogen atoms on different sites, relative to the position of the
      nitrogen atom, is explicitly taken into account. Both non-chiral and chiral
      geometries are analyzed. The obtained band structure shows that the non-chiral
      (6,0) nanotube is a semimetal under all different doping and adsorption
      configurations treated. The non-chiral (10,0) nanotube behaves mostly as a
      semiconductor, with the band gap width modulated by nitrogen doping and the
      relative position of the adsorbed hydrogen atom. The increase of substitutional N
      doping from one to three atoms per cell turns a (6,5) single-walled carbon
      nanotube from a semiconductor into a semimetal at zero temperature. Optical
      absorption related to carrier transitions between the calculated states is
      investigated from the imaginary part of the dielectric function, constructed with
      the use of the calculated Kohn-Sham states. The importance of the variation of
      the relative position of the adsorbed hydrogen atom on the chemical and physical
      properties investigated is particularly highlighted.

PMID- 27711504
TI  - Thermoelectric properties of fullerene-based junctions: a first-principles study.
AB  - This study is built on density functional calculations in combination with the
      non-equilibrium Green's function, and we probe the thermoelectric transport
      mechanisms through C60 molecules anchored to Al nano-electrodes in three
      different ways, such as, the planar, pyramidal, and asymmetric surfaces. When the
      electrode is switched from the planar and pyramidal surfaces, the electrical
      conductance (sigma) and electron's thermal conductance (kappael) decrease almost
      two orders of magnitude due to the reduction of the molecule-electrode contact
      coupling, whereas the Seebeck coefficients (S) are reduced by ~55%. Furthermore,
      the maximum electron's thermoelectric figure of merit (ZelT = S2sigmaT/kappael,
      assuming a vanishing phonon's thermal conductance) is about 0.12 in the
      asymmetric junction. In particular, all sigma, S, kappael, and ZelT increase
      along with the average temperature (T) in all C60-junctions, although their
      growth is really quite negligible in the pyramidal junction because the Fermi
      level is far away from the frontier orbitals. In addition, when the strain
      increases from the compressive (-1.0 A) to tensile (1.0 A) strain, the Seebeck
      coefficient in the planar junction increases drastically, while the Seebeck
      coefficients in the asymmetric and pyramidal junctions reach their maximum values
      at 0.2 A tensile and -0.4 A compressive strains, respectively. This is because
      the Seebeck coefficient is inversely proportional to the magnitudes and
      proportional to the slopes of the transmission spectrum around the Fermi level.
      Finally, it is found that the shift of the Fermi level is an effective scheme to
      obtain the maximum ZelT of any molecular junction, including fullerene-based
      junctions.

PMID- 27711505
TI  - Comment on T. Stauch, A. Dreuw, "Stiff-stilbene photoswitch ruptures bonds not by
      pulling but by local heating", Phys. Chem. Chem. Phys., 2016, 18, 15848.

PMID- 27711506
TI  - Functionalization of two-dimensional phthalo-carbonitride with metal atoms.
AB  - Two-dimensional (2D) carbonitrides have attracted intense interest because of
      their intriguing physical and chemical properties. One such 2D system is the so
      called phthalo-carbonitride (pc-C3N2) with stoichiometry C3N2 and an extended
      network of phthalocyanine-like cores. Here we use first-principles calculations
      to study pc-C3N2 sheets with Al, Zn, or Cu atoms attached at the cores. We
      describe the structural details of various possible geometries and probe the
      electronic properties of the most stable configurations. The decorated sheets are
      metallic, with the exception of the Zn case, which is a semiconductor with a
      small energy band gap. Moreover, the Cu-laden monolayers bear finite
      magnetization. These key properties highlight the potential of C3N2-based 2D
      materials as multi-functional components in various applications.

PMID- 27711507
TI  - Versatile fabrication of a superhydrophobic and ultralight cellulose-based
      aerogel for oil spillage clean-up.
AB  - To deal with marine oil spillage and chemical leakage issues, a highly efficient
      absorbent (cellulose based aerogel) with a low density (rho < 0.034 g cm-3, phi >
      98.5%) and high mechanical strength was fabricated via a novel physical-chemical
      foaming method, plasma treatment and subsequent silane modification process. This
      aerogel has a perfect 3D skeleton and interconnected pores similar to honeycomb,
      which are favorable to oil adsorption and storage. More importantly, without
      introducing additional micro/nanoparticles, the rough micro/nano structure of the
      surface was directly constructed using plasma irradiation in this study. The low
      surface energy substrate was further introduced using a simple physical-soaking
      method and the resulting aerogel exhibited excellent superhydrophobicity (WCA >
      156 degrees ) and superoleophilicity (OCA = 0 degrees ), which can selectively
      and efficiently absorb various oils or organic solvents from polluted water. In
      addition, this aerogel has a high storage capacity and absorption capacity (up to
      4300% and 99% of its weight and volume, respectively). More interestingly, this
      aerogel exhibits excellent mechanical abrasion resistance and corrosion
      resistance even in strong acid, alkali solution and salt marine environment. The
      aerogel could be reused more than 30 times after removal of the absorbed oil by
      rinsing with ethanol.

PMID- 27711508
TI  - How do random superficial defects influence the electro-oxidation of glycerol on
      Pt(111) surfaces?
AB  - The glycerol electrooxidation reaction (GEOR) has attracted huge interest in the
      last decade due to the very low price and availability of this polyol. In this
      work, we studied the GEOR on Pt(111) electrodes by introducing different
      densities of random defects. Our results showed that the generation of defects on
      Pt(111) slightly modified the GEOR onset potential, however it generates changes
      in the voltammetric oxidation charges and also in the relative production of CO2
      to carbonyl containing compounds, C[double bond, length as m-dash]O. The
      voltammetric profiles in the forward scan show two oxidation peaks. FTIR data
      show that the first one is connected with the GlOH dissociative adsorption to
      form CO (and others intermediates) while the second one, at higher potentials,
      matches the onsets of the CO oxidation to CO2 and the C[double bond, length as m
      dash]O production. FTIR also confirms that the lower activity of defected
      electrodes at lower potentials is connected to a higher CO poisoning. DFT
      calculations show that the presence of CO molecules on a Pt defected surface
      keeps water and GlOH molecules far from the surface and linked by H bonds. This
      paper is the last of a series of three works where we explore the GEOR on an
      important number of different Pt surfaces. These works show that it is difficult
      to oxidize GlOH at potentials lower than 0.6 V (under our experimental
      conditions) without suffering an important electrode poisoning (mainly by CO).
      Since the structure of nanoparticles might be mimicked by defected single
      crystals, these sets of reports provide a considerable amount of information
      concerning the influence of such surfaces towards GlOH reaction in acidic media.
      Therefore, if the well-known "nano"-effect does not produce substantial changes
      in the activity of Pt materials, they are not useful to be applied in a Direct
      Glycerol Fuel Cell (DGFC). On the other hand, it is very interesting that the
      density of electrode defects permits us to tune the relative production of CO2 to
      C[double bond, length as m-dash]O.

PMID- 27711509
TI  - Nonresonant electronic transitions induced by vibrational motion in light-induced
      potentials.
AB  - We find a new mechanism of electronic population inversion using strong
      femtosecond pulses, where the transfer is mediated by vibrational motion on a
      light-induced potential. The process can be achieved with a single pulse tuning
      its frequency to the red of the Franck-Condon window. We show the determinant
      role that the gradient of the transition dipole moment can play on the dynamics,
      and extend the method to multiphoton processes with odd number of pulses. As an
      example, we show how the scheme can be applied to population inversion in Na2.

PMID- 27711510
TI  - An attempt to correlate surface physics with chemical properties: molecular beam
      and Kelvin probe investigations of Ce1-xZrxO2 thin films.
AB  - What is the correlation between physical properties of the surfaces (such as
      surface potential, electronic nature of the surface), and chemical and catalysis
      properties (such as chemisorption, sticking probability of surface)? An attempt
      has been made to explore any correlation that might exist between the physical
      and chemical properties of thin film surfaces. Kelvin probe microscopy (KPM) and
      the molecular beam (MB) methods were employed to carry out the surface potential,
      and oxygen adsorption and oxygen storage capacity (OSC) measurements on Ce1
      xZrxO2 thin films. A sol-gel synthesis procedure and spin-coating deposition
      method have been applied to make continuous nanocrystalline Ce1-xZrxO2 (x = 0-1)
      (CZ) thin films with uniform thickness (35-50 nm); however, surface roughness and
      porosity inherently changes with CZ composition. MB studies of O2 adsorption on
      CZ reveal high OSC for Ce0.9Zr0.1O2, which also exhibits highly porous and
      significantly rough surface characteristics. The surface potential observed from
      KPM studies varied between 30 and 80 mV, with Ce-rich compositions exhibiting the
      highest surface potential. Surface potential shows large changes after reduction
      or oxidation of the CZ film demonstrating the influence of Ce3+/Ce4+ on surface
      potential, which is also a key to catalytic activity for ceria-based catalysts.
      The surface potential measured from KPM and the OSC measured from MB vary
      linearly and they depend on the Ce3+/Ce4+ ratio. More and detailed studies are
      suggested to arrive at a correlation between the physical and chemical properties
      of the surfaces.

PMID- 27711511
TI  - Directional dependence of the electronic and transport properties of 2D borophene
      and borophane.
AB  - Very recently two dimensional layers of boron atoms, so called borophene, have
      been successfully synthesized. It presents a metallic band structure, with a
      strong anisotropic character. Upon further hydrogen adsorption a new material is
      obtained, borophane; giving rise to a Dirac cone structure like the one in
      graphene. We have performed a first-principles study of the electronic and
      transport properties of borophene and borophane through the Landauer-Buttiker
      formalism. We find that borophene presents an electronic current two orders of
      magnitude larger than borophane. In addition we verified the direction dependence
      of the electronic current in two perpendicular directions, namely, Ix and Iy;
      where for both systems, we found a current ratio, eta = Ix/Iy, of around 2.
      Aiming to control such a current anisotropy, eta, we performed a study of its
      dependence with respect to an external strain. Where, by stretching the borophane
      sheet, eta increases by 11% for a bias voltage of 50 mV.

PMID- 27711512
TI  - The complex behavior of the Pd7 cluster supported on TiO2(110) during CO
      oxidation: adsorbate-driven promoting effect.
AB  - Using the TiO2(110)-supported Pd7 cluster as a model catalyst, we have identified
      from density functional theory calculations that the dynamics of supported metal
      nanoparticles, particularly at the sub-nanometer scale, can be complex under
      reactive environments. Increasing the CO coverage can induce a structural
      transformation from Pd7-3D/TiO2(110) at low coverage to Pd7-2D/TiO2(110) at the
      saturation coverage wherein CO saturation-driven Pd7-2D/TiO2(110) structure
      displays superior CO oxidation activity at the interfacial sites, which are
      highly active for catalyzing O2 dissociation and CO oxidation via bifunctional
      synergy.

PMID- 27711513
TI  - 17O MAS NMR studies of oxo-based olefin metathesis catalysts: a critical
      assessment of signal enhancement methods.
AB  - The DFS enhancement method as applied to 17O MAS NMR was critically assessed,
      first on NaPO3, a simple binary glass system, and in a second step, on a series
      of catalysis-related organometallic molecules and materials. The robustness of
      DFS was investigated for the wide range of anisotropic parameters (quadrupolar
      coupling and chemical shift anisotropy) encountered in these samples. Emphasis
      has been put on the variation of signal enhancements with respect to the DFS
      final sweep frequency, pulse amplitude and pulse duration, while line shape
      distortion issues were also addressed. Finally, the robustness of DFS enhancement
      of the 17O MAS NMR signal is shown through its successful application to silica
      supported olefin metathesis catalysts.

PMID- 27711514
TI  - Growth patterns and structural motifs of cadmium clusters with up to 60 atoms:
      disordered or not?
AB  - Using two different approaches, the structures of Cdn clusters are optimized. At
      first, parameterized density-functional calculations using the DFTB method in
      combination with evolutionary algorithms provide one set of candidate structures.
      Second, earlier proposed structures based on the Gupta potential provide a second
      set. Subsequently, all structures of each set are re-optimized using parameter
      free density-functional calculations. It turned out that those based on the DFTB
      calculations in almost all cases were those of the lowest total energy. By
      analysing the structural properties as a function of cluster size information on
      growth patterns can be extracted. Thereby, the results show a certain preference
      that the atoms of the inner parts have surroundings as found in bulk hcp Cd.
      Furthermore, for larger size ranges, we could identify a specific growth pattern,
      implying that most of these clusters cannot be classified as being disordered.
      The results show also that the 4d electrons have only a weak influence on the
      properties of the clusters that, however, is so strong that a jellium-like model
      occasionally becomes inaccurate in describing the properties. In particular, the
      question at which size the clusters can be considered to be metallic becomes non
      trivial to answer. Further arguments based on a comparison of the HOMO-LUMO gaps
      with the Kubo gap, however, suggested the non-metallic properties in the studied
      size range.

PMID- 27711515
TI  - Large enhancement in photocurrent by Mn doping in CdSe/ZTO quantum dot sensitized
      solar cells.
AB  - We find a large enhancement in the efficiency of CdSe quantum dot sensitized
      solar cells by doping with manganese. In the presence of Mn impurities in
      relatively small concentrations (2.3%) the photoelectric current increases by up
      to 190%. The average photocurrent enhancement is about 160%. This effect cannot
      be explained by a light absorption mechanism because the experimental and
      theoretical absorption spectra demonstrate that there is no change in the
      absorption coefficient in the presence of the Mn impurities. To explain such a
      large increase in the injection current we propose a tunneling mechanism of
      electron injection from the quantum dot LUMO state to the Zn2SnO4 (ZTO)
      semiconductor photoanode. The calculated enhancement is approximately equal to
      150% which is very close to the experimental average value of 160%. The relative
      discrepancy between the calculated and experimentally measured ratios of the IPCE
      currents is only 6.25%. For other mechanisms (such as electron trapping, etc.)
      the remaining 6.25% cannot explain the large change in the experimental IPCE.
      Thus we have indirectly proved that electron tunneling is the major mechanism of
      photocurrent enhancement. This work proposes a new approach for a significant
      improvement in the efficiency of quantum dot sensitized solar cells.

PMID- 27711516
TI  - Phosphine passivated gold clusters: how charge transfer affects electronic
      structure and stability.
AB  - A systematic evaluation of small phosphine ligand-protected gold clusters with
      six to nine gold atoms using density functional theory with dispersion correction
      has been performed in order to understand the major factors determining
      stability, including its size, shape, and charge dependence. We show that the
      charge per atom of the cluster is much more important for the interaction between
      the ligand shell and gold cluster than the system size. Thus, strong charge
      transfer effects determine the binding strength between the ligand shell and
      cluster. The clusters in this series are all non-spherical and exhibit large HOMO
      LUMO gaps (above 2.7 eV). Analysis of the delocalized nature of the electronic
      states at the centre of the clusters demonstrates the presence of nascent
      superatomic states. However the number of delocalized electrons in these systems
      is significantly influenced by the charge transfer from the phosphine ligands,
      contrary to the usual accounting rule for superatom complex systems. Thus, not
      only electron withdrawing but also charge transfer effects should be considered
      to influence the superatomic structure of charged ligand surrounded clusters. In
      consequence in the phosphine gold cluster series under consideration the systems
      Au7(PPh3)7+ and Au8(PPh3)82+ exhibit nearly fully filled S and P states and the
      HOMO-LUMO gap increases by 0.2 eV and 0.9 eV, respectively. The interpretation
      for the stability of the gold phosphine systems is in agreement with experimental
      results and demonstrates the importance of the superatomic concept.

PMID- 27711517
TI  - Wetting behavior of water on silicon carbide polar surfaces.
AB  - Technically important wide band-gap semiconductors such as GaN, AlN, ZnO and SiC
      are crystallized in polar structures. Taking SiC as an example, we investigate
      the effect of surface polarity on the wetting behavior by water using experiments
      and molecular dynamic simulations. It is found that the contact angle (CA) of
      deionized water on the carbon-face (C-face) is significantly larger than that on
      the silicon-face (Si-face) for both 6H-SiC and 4H-SiC, while the CA of
      tetrachloromethane is almost the same on these two faces. This finding clearly
      indicates that polar interactions between water and SiC induce such a large
      difference in the CA. Extensive molecular dynamics simulations suggest that a
      larger CA on the C-face than that on the Si-face is resulted from the different
      charge agglomeration on the two faces. These results will not only be helpful in
      improving the state of the art processes such as rinsing and wet etching in
      device fabrication, but also offer a reliable method to determine the polarity of
      SiC crystals quickly, simply, accurately and nondestructively, which is easily
      extendable for the measurement of other polar crystals.

PMID- 27711518
TI  - Fast and slow dynamics and the local structure of liquid and supercooled water
      next to a hydrophobic amino acid.
AB  - We study, through molecular dynamics simulations, the structure and orientational
      dynamics of water next to a blocked hydrophobic amino acid, valine (Val), above
      and below the freezing point of water. The structure and the orientational
      dynamics of waters with four water neighbors (4WN) and less than four water
      neighbors (L4WN) in the Val's coordination sphere are deconvoluted. We find that
      in spite of the excluded volume effects waters with L4WN have faster librational
      dynamics than bulk water, reminiscent of water at the liquid-vapor interface, and
      faster orientational dynamics than waters with 4WN, at every temperature.
      Furthermore, our results show that the pronounced decrease of the orientational
      retardation factor below ~255 K observed experimentally is mostly caused by the
      acceleration of the orientational dynamics of waters with L4WN, while waters with
      4WN exhibit only moderate acceleration. The differences between the hydrogen-bond
      acceptor switching mechanism in the shell and the bulk are also analyzed, and no
      evidence of especially slow OH groups neither in the 4WN nor in the L4WN
      populations is found. Finally, we show that waters with 4WN have higher
      tetrahedrality than bulk water at every temperature although this difference
      decreases at both high and low temperatures.

PMID- 27711519
TI  - Theoretical calculation of the vibrational state dependent photodetachment
      spectra of X-H2O, X = F, Cl, Br.
AB  - Vibrational spectra of X-H2O (X = F, Cl, Br) were simulated using full
      dimensional vibrational calculations using quantum chemistry potential energy
      surfaces. Furthermore, utilizing the reflection approximation, we simulated the
      photodetachment spectra obtained from different vibrational excited states. From
      these spectra, we can observe changes in the hydrogen bond interaction between
      the anion and the neutral XH2O system. Notably, for F-H2O, the excitation of the
      ionic hydrogen bonded (IHB) OH stretching vibration generates a large tail on the
      low energy side of the photodetachment spectra compared to the detachment from
      the zero-point vibration state. This shows that the IHB OH stretching vibration
      of F-H2O causes charge delocalization from F- to the oxygen atom in H2O, and that
      the photodetachment from FHOH- occurs at lower energies.

PMID- 27711520
TI  - The possible formation of a magnetic FeS2 phase in the two-dimensional MoS2
      matrix.
AB  - The possibility of a FeS2 phase formation in the 2D MoS2 structure was
      investigated by an ab initio DFT approach. Various concentrations of FeS2 in MoS2
      have been analyzed, and it is shown that the energy favorable structures of the
      Mo1-xFexS2 composition are in-plane hybrid phases, FeS2 and MoS2 domains. After
      increasing the Fe/Mo concentration ratio up to 0.68, a complete transformation of
      the whole structure is predicted. We have found that the introduction of only a
      small amount of Fe atoms leads to a change in the electronic and magnetic
      properties of the film. An increase of the FeS2 nucleus size leads to the nearly
      monotonous increase of the magnetic moment governed by the exponential law.

PMID- 27711522
TI  - The study of electron transfer reactions in a dendrimeric assembly: proper
      utilization of dendrimer fluorescence.
AB  - The PAMAM dendrimer with a cage like structure acts as an excellent electron
      donor in the presence of an electron deficient molecule. Electron transfer (ET)
      causes significant quenching of dendrimer fluorescence. Trapping of quencher
      molecules within the dendrimer cage helps ET to take place through an expeditious
      route. Utilization of intrinsic fluorescence and sensing applications of
      dendrimers have been established here.

PMID- 27711521
TI  - Photoinduced water splitting in pyridine water clusters.
AB  - Ab initio calculations predict that pyridine (Py) can act as a photo-catalyst to
      split water by the absorption of a UV photon following the reaction Py-H2O + hnu 
      > PyH + OH. To test this prediction, we performed two types of experiments: in
      the first, we characterize the electronic spectroscopy of the PyH radical in the
      gas phase. In the second, we evidence the reaction through the UV excitation of
      molecular Py-(H2O)n clusters obtained in a supersonic expansion and monitoring
      the PyH reaction product. The results show unambiguously that PyH is produced,
      and thus that water is split using pyridine as a photo-catalyst.

PMID- 27711524
TI  - Chiral recognition by fullerenes: CHFClBr enantiomers in the C82 cage.
AB  - Density-functional theory and symmetry-adapted perturbation theory calculations
      on complexes of the enantiomers of CHFClBr with the most stable isomer of C82-3
      fullerene show that despite the guests being too large for the host cage, they
      are nevertheless stabilized by electrostatic interactions. The complexation leads
      to considerable strain on the cage and the guests accompanied by compression of
      the bonds of the guest molecule, resulting in considerable complexation-induced
      changes in the infrared (IR), vibrational circular dichroism (VCD), nuclear
      magnetic resonance (NMR), and UV-vis spectra. The effect of chiral recognition is
      pronounced only for the 19F signal in the NMR spectra and in a sign reversal of
      the rotational strength of the nuCH stretching vibration of S-CHFClBr@C82-3 in
      the VCD spectrum as compared to that of the free guest, making the sign of this
      band for the C82 complexes with the S- and R-guest enantiomers the same. This is
      a surprising result since vibrational circular dichroism is considered a reliable
      method for determining the absolute chirality of small molecules and for
      establishing dominant conformations in biopolymers.

PMID- 27711525
TI  - Structural movies of the gradual spin-crossover in a molecular complex at various
      physical scales.
AB  - The thermally induced Spin-CrossOver (SCO) undergone by the mononuclear iron(ii)
      complex [Fe(PM-AzA)2(NCS)2] (PM = N-2'-pyridylmethylene, AzA = 4
      (phenylazo)aniline) is fully pictured by a quasi-continuous structural
      determination all along the spin-state modification within the sample. This large
      scale multi-temperature Single-Crystal X-Ray Diffraction (SCXRD) investigation
      leads to making structural movies. The latter reveal or confirm some features of
      the SCO that are subsequently validated by the same systematic investigation
      performed on a zinc isostructural analogue complex. Notably, the continuous views
      of the temperature dependencies of the unit-cell parameters, the dilatation
      tensors, the metal coordination sphere geometry and the intermolecular distances
      confirm a few of the structure-property relationships already known for SCO
      materials. In parallel, the examination of the temperature dependencies of the
      atomic coordinates and the atomic displacement parameters reveals unexpected
      behaviours in this gradual SCO material such as antagonistic atomic movements due
      to the single SCO and the pure thermal effects.

PMID- 27711526
TI  - Effect of chain microstructure on self-assembly and emulsification of amphiphilic
      poly(acrylic acid)-polystyrene copolymers.
AB  - In this study, a series of random copolymer poly(acrylic acid-co-styrene) (P(AA
      co-St)) and block copolymer poly(acrylic acid)-b-polystyrene (PAA-b-PSt) with
      similar chemical composition but different chain microstructure were synthesized.
      The self-assembly behavior of random and block copolymers in selective solvent
      was investigated, and the structural evaluation of random and block copolymers
      micelles was carried out by transmission electron microscopy (TEM), dynamic light
      scattering (DLS) measurement, and X-ray photoelectron spectroscopy (XPS).
      Moreover, together with experimental characterization, the theoretical method
      dissipative particle dynamics (DPD) approach was applied to investigate the
      morphological structures of micelles composed from random and block copolymers.
      Results revealed that the structure of polymeric micelles is significantly
      affected by the distribution sequence of hydrophilic and hydrophobic monomers in
      copolymer chains. Furthermore, polymeric micelles based on P(AA-co-St) and PAA-b
      PSt with about 50 mol% hydrophilic composition were chosen as the model to
      investigate the influence of micellar structure on emulsifying performance. For
      PAA-b-PSt micelles (B48), stable water-in-oil (w/o) emulsions could only obtained
      when the pH values were lower than 5. As a comparison, the P(AA-co-St) micelles
      (R49) had an excellent emulsification performance at 4-10 pH, and the pH-induced
      phase inversion derived from obtained emulsions observed at pH higher than 6.
      Preliminary results confirm that the micellar structure controlled by chain
      microstructure plays an important role in the interface behavior of polymer
      micelles. Compared with PAA-b-PSt micelles, P(AA-co-St) micelles have better
      interfacial performance and are more tailorable and controllable; thus they can
      be used as a model for further study of polymeric particulate emulsifiers. This
      paper provides new insight into the principles governing extremely high
      emulsifying efficiency of polymeric particulate emulsifiers and pH-responsive
      properties of the formed emulsions.

PMID- 27711528
TI  - Energy harvesting and conversion mechanisms for intrinsic upconverted mechano
      persistent luminescence in CaZnOS.
AB  - We interpreted the mechanisms of energy harvesting and conversion for intrinsic
      upconverted mechano-persistent luminescence in CaZnOS through a native point
      defects study. We found that vacancy defects such as Zn and O vacancies, as well
      as Schottky pair defects, act as energy harvesting centers; they are very readily
      formed and very active. They are found to be extra deep electron or hole trap
      levels near the valence or conduction band edges, respectively. This leads to a
      coupling and exchange effect to continuously collect and transport host charges
      along a path via localized states to deep recombination levels. The initiating
      energy barrier is small and can be overcome by ambient thermal stimulation or
      quantum tunneling. Native activators such as V, V, and V function as energy
      conversion centers to transfer energy into photon emissions. This gives a solid
      theoretical reference for developing upconverted mechano-persistent luminescence.

PMID- 27711527
TI  - Determination of the local structure of CsBi4-xPbxTe6 (x = 0, 0.5) by X-ray
      absorption spectroscopy.
AB  - We have studied the local structure and valence electronic unoccupied states of
      thermoelectric CsBi4Te6 and superconducting CsBi3.5Pb0.5Te6 (Tc ~ 3 K) by
      extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge
      structure (XANES) measurements. The Bi-L3 edge EXAFS reveals wide Bi-Te distance
      distribution for both compounds indicating complex atomic arrangements in the
      studied system. The mean square relative displacements (MSRDs) of the Bi-Te bond
      distances appear largely increased in Pb substituted system due to larger overall
      local disorder, however, one of the Bi-Te bonds shows a reduced disorder. On the
      other hand, the Bi-L3 edge XANES is hardly affected by Pb substitution while the
      Te-L1 edge XANES reveals increased density of unoccupied Te 5p states. This
      suggests that the carriers introduced by the Pb substitution in CsBi4-xPbxTe6
      preferentially goes on Te sites. Similarly, the Cs-L3 edge XANES also shows small
      changes due to Pb-substitution and reduced local disorder indicated by the
      reduced width of the Cs-L3 edge white line. We have also shown that the X-ray
      photoemission spectroscopy (XPS) measurements on various electronic core levels
      are in a qualitative agreement with the XANES results. These findings are
      consistent with carrier doping and a reduced disorder in one direction to be
      likely factors to drive the thermoelectric CsBi4Te6 into a bulk superconductor by
      Pb-substitution in CsBi4-xPbxTe6.

PMID- 27711529
TI  - Spatially resolved surface valence gradient and structural transformation of
      lithium transition metal oxides in lithium-ion batteries.
AB  - Layered lithium transition metal oxides are one of the most important types of
      cathode materials in lithium-ion batteries (LIBs) that possess high capacity and
      relatively low cost. Nevertheless, these layered cathode materials suffer
      structural changes during electrochemical cycling that could adversely affect the
      battery performance. Clear explanations of the cathode degradation process and
      its initiation, however, are still under debate and not yet fully understood. We
      herein systematically investigate the chemical evolution and structural
      transformation of the LiNixMnyCo1-x-yO2 (NMC) cathode material in order to
      understand the battery performance deterioration driven by the cathode
      degradation upon cycling. Using high-resolution electron energy loss spectroscopy
      (HR-EELS) we clarify the role of transition metals in the charge compensation
      mechanism, particularly the controversial Ni2+ (active) and Co3+ (stable) ions,
      at different states-of-charge (SOC) under 4.6 V operation voltage. The cathode
      evolution is studied in detail from the first-charge to long-term cycling using
      complementary diagnostic tools. With the bulk sensitive 7Li nuclear magnetic
      resonance (NMR) measurements, we show that the local ordering of transition metal
      and Li layers (R3[combining macron]m structure) is well retained in the bulk
      material upon cycling. In complement to the bulk measurements, we locally probe
      the valence state distribution of cations and the surface structure of NMC
      particles using EELS and scanning transmission electron microscopy (STEM). The
      results reveal that the surface evolution of NMC is initiated in the first
      charging step with a surface reduction layer formed at the particle surface. The
      NMC surface undergoes phase transformation from the layered structure to a poor
      electronic and ionic conducting transition-metal oxide rock-salt phase
      (R3[combining macron]m -> Fm3[combining macron]m), accompanied by irreversible
      lithium and oxygen loss. In addition to the electrochemical cycling effect,
      electrolyte exposure also shows non-negligible influence on cathode surface
      degradation. These chemical and structural changes of the NMC cathode could
      contribute to the first-cycle coulombic inefficiency, restrict the charge
      transfer characteristics and ultimately impact the cell capacity.

PMID- 27711533
TI  - QM/MM calculations on a newly synthesised oxyluciferin substrate: new insights
      into the conformational effect.
AB  - In this publication we conduct calculations on a newly synthesised red-shifted
      emitter of luciferin in order to understand what are the main contributions to
      the colour-shifting emission. Indeed the bioluminescent system, especially from
      fireflies, is one of the main resources for medical imaging but its efficiency
      greatly depends on the wavelength of the emission. We performed classical
      molecular dynamics followed by quantum mechanics/molecular mechanics (QM/MM)
      calculations, with either density functional theory or multiconfigurational
      reference second-order perturbation theory on different emitters to obtain
      bioluminescence emission. We analysed the calculations and investigated the
      effects which play a non-negligible role in the emission, like the effect of the
      surroundings or the effect of the conformation of the emitter. Finally, in the
      absence of crystallographic structures, we proposed the most likely conformation
      for the emitter in the bioluminescence process.

PMID- 27711534
TI  - Helium droplet infrared spectroscopy of glycine and glycine-water aggregates.
AB  - Infrared absorption spectra of glycine and glycine-water aggregates embedded in
      superfluid helium nanodroplets were recorded in the frequency range 1000-1450 cm
      1. For glycine monomer, absorption bands were observed at 1106 cm-1, 1134 cm-1,
      and 1389 cm-1. These bands were assigned to the C-OH stretch mode of the glycine
      conformers I, III and II, respectively. For glycine-water aggregates, we observed
      two bands at 1209 cm-1 and 1410 cm-1 which we assign to distinct conformers of
      glycine-H2O. In all cases, the water is found to preferentially bind to the
      carboxyl group of the glycine.

PMID- 27711532
TI  - EPR characterization of Mn(ii) complexes for distance determination with pulsed
      dipolar spectroscopy.
AB  - The four Mn(ii) complexes Mn-DOTA, Mn-TAHA, Mn-PyMTA, and Mn-NO3Py were
      characterized by electron paramagnetic resonance (EPR), electron-nuclear double
      resonance (ENDOR), and relaxation measurements, to predict their relative
      performance in the EPR pulse dipolar spectroscopy (PDS) experiments. High spin
      density localization on the metal ions was proven by ENDOR on 1H, D, 14N, and
      55Mn nuclei. The transverse relaxation of the Mn(ii) complexes appears to be slow
      enough for PDS-based spin-spin distance determination. Rather advantageous ratios
      of T1/Tm were measured allowing for good relaxation induced dipolar modulation
      enhancement (RIDME) performance and, in general, fast shot repetitions in any PDS
      experiment. Relaxation properties of the Mn(ii) complexes correlate with the
      strengths of their zero field splitting (ZFS). Further, a comparison of Mn(ii)
      DOTA and Gd(iii)-DOTA based spin labels is presented. The RIDME technique to
      measure nanometer-range Mn(ii)-Mn(ii) distances in biomolecules is discussed as
      an alternative to the well-known DEER technique that often appears challenging in
      cases of metal-metal distance measurements. The use of a modified kernel function
      that includes dipolar harmonic overtones allows model-free computation of the
      Mn(ii)-Mn(ii) distance distributions. Mn(ii)-Mn(ii) distances are computed from
      RIDME data of Mn-rulers consisting of two Mn-PyMTA complexes connected by a
      rodlike spacer of defined length. Level crossing effects seem to have only a weak
      influence on the distance distributions computed from this set of Mn(ii)-Mn(ii)
      RIDME data.

PMID- 27711535
TI  - Temperature dependence of the reaction of anti-CH3CHOO with water vapor.
AB  - The kinetics of the reaction of anti-CH3CHOO with water vapor were investigated
      using transient UV absorption spectroscopy at temperatures from 288 to 328 K and
      500 Torr. We found that both the water monomer and the water dimer react with
      anti-CH3CHOO. The rate coefficients of the reaction of the water monomer and
      dimer with anti-CH3CHOO at 298 K were determined to be (1.31 +/- 0.26) * 10-14
      cm3 s-1 and (4.40 +/- 0.29) * 10-11 cm3 s-1, respectively. Furthermore, for the
      water dimer reaction, we observed very large negative temperature dependence with
      an activation energy of -12.17 +/- 0.66 kcal mol-1. On the other hand, the
      monomer reaction showed minimal temperature dependence with nearly zero
      activation energy. At atmospherically relevant humidity, in opposition to
      previous experiments conducted for CH2OO in which water dimer reaction
      predominates at room temperature, for anti-CH3CHOO, the water monomer reaction
      can contribute significantly (~30% of the reaction with water vapor at relative
      humidity RH = 40% and 298 K). These results show that substitution of an alkyl
      group can greatly affect the reaction of Criegee intermediates with water vapor,
      especially changing the contributions of water monomer and dimer reactions.

PMID- 27711536
TI  - Post-perovskite CaIrO3: a conventional Slater type antiferromagnetic insulator.
AB  - To resolve the controversy of whether or not the origin of an electronic gap in
      antiferromagnetic post-perovskite (pPv) CaIrO3 is due to Coulomb repulsion or
      spin-orbit coupling, and/or both, we have performed comprehensive full potential
      density functional theory based calculations. A rather consistent electronic
      structure, which explains the origin and magnitude of the electronic gap, inter
      band d-d transition energies, high thermopower and large magneto-crystalline
      anisotropy, is obtained with the use of a modified Becke-Johnson (mBJ) exchange
      potential. Fundamentally, mBJ calculations correctly capture the strong interplay
      of the crystal field and long range antiferromagnetic ordering of Ir spins as the
      mechanism that drives pPv-CaIrO3 to an insulating state. Based on our findings,
      we propose that pPv-CaIrO3 is a conventional Slater type antiferromagnetic
      insulator.

PMID- 27711537
TI  - Ab initio molecular dynamics study of Se(iv) species in aqueous environment.
AB  - An ab initio molecular dynamics investigation is carried out on various water
      borne Se(iv) species, H2SeO3, HSeO3- and SeO32-, in aqueous environment.
      Consistent with the reported acid dissociation constants, in neutral solution
      H2SeO3 exchanges protons with the surrounding water molecules establishing a
      dynamic equilibrium with HSeO3-. The SeO32- species is found to be stable only in
      basic environment, which is emulated in the present simulation through
      introducing a hydroxide ion, OH-, in the system. The hydration structure,
      hydrogen bonding and spectroscopic signatures of the species are comprehensively
      analyzed. The influence of the solute's hydration structure on the structural and
      dynamic response of the solvent is discussed. The correlation between the
      strength as well as the number of hydrogen bonds accepted by the solute on its
      vibrational properties are analyzed.

PMID- 27711538
TI  - Concerted nitrogen inversion and hydrogen bonding to Glu451 are responsible for
      protein-controlled suppression of the reverse reaction in human DPP III.
AB  - Human dipeptidyl-peptidase III (h.DPP III) is a zinc-exopeptidase that hydrolyses
      dipeptides from the N-terminus of its substrates. Its mechanism of action was
      assumed to be similar to that of thermolysin, but was never thoroughly
      investigated. This study presents the first insight into the reaction mechanism
      of h.DPP III, determined on the model and real (hydrated enzyme with Leu
      enkephalin bound in the active site) systems. The Glu451-assisted water addition
      on amide carbon atoms and nitrogen inversion (i.e. change of pyramidalization on
      the leaving nitrogen) are shown to be the rate-determining steps with the
      activation energies in a good agreement with the experimental results for the Leu
      enkephalin hydrolysis. The energy barrier for nucleophilic attack is about 28 kJ
      mol-1, while barriers for the N-inversion differ as a consequence of the number
      of hydrogen bonds that have to be changed, which is smaller in the model active
      site than in the solvated enzyme. Although precisely defined geometry of the
      enzyme binding site puts an additional restraint on the hydrogen bonding
      interactions, at the same time it stimulates the forward reaction towards the
      final hydrolytic product. Namely, different from the model, the N-inversion is in
      a concerted fashion followed by favourable hydrogen bonding with Glu451 that
      immediately "locks" the system into the configuration where reversion to the
      enzyme-substrate complex is hardly achievable. Therefore we propose that the
      functional significance of DPP III is dual: to lower the energy barrier of the
      peptide hydrolysis and to suppress the reverse reaction.

PMID- 27711539
TI  - Computational investigation into the gas-phase ozonolysis of the conjugated
      monoterpene alpha-phellandrene.
AB  - Reaction with ozone is a major atmospheric sink for alpha-phellandrene, a
      monoterpene found in both indoor and outdoor environments, however experimental
      literature concerning the reaction is scarce. In this study, high-level G4(MP2)
      quantum chemical calculations are used to theoretically characterise the reaction
      of ozone with both double bonds in alpha-phellandrene for the first time. Results
      show that addition of ozone to the least substituted double bond in the
      conjugated system is preferred. Following addition, thermal and chemically
      activated unimolecular reactions, including the so-called hydroperoxide and ester
      or 'hot' acid channels, and internal cyclisation reactions, are characterised to
      major first generation products. Conjugation present in alpha-phellandrene allows
      two favourable Criegee intermediate reaction pathways to proceed that have not
      previously been considered in the literature; namely a 1,6-allyl resonance
      stabilised hydrogen shift and intramolecular dioxirane isomerisation to an
      epoxide. These channels are expected to play an important role alongside
      conventional routes in the ozonolysis of a-phellandrene. Computational
      characterisation of the potential energy surface thus provides insight into this
      previously unstudied system, and will aid future mechanism development and
      experimental interpretation involving alpha-phellandrene and structurally similar
      species, to which the results are expected to extend.

PMID- 27711540
TI  - Systematic design and application of unimolecular star-like block copolymer
      micelles: a coarse-grained simulation study.
AB  - Unimolecular polymeric micelles have several features, such as thermodynamic
      stability, small particle size, biocompatibility, and the ability to internalize
      hydrophobic molecules. These micelles have recently attracted significant
      attention in various applications, such as nano-reactors, catalysis, and drug
      delivery. However, few attempts have explored the formation mechanisms and
      conditions of unimolecular micelles due to limited experimental techniques. In
      this study, a unimolecular micelle system formed from beta-cyclodextrin-graft
      {poly(lactide)-block-poly(2-(dimethylamino) ethyl multimethacrylate)-block
      poly[oligo (2-ethyl-2-oxazoline) methacrylate]} beta-CD-g-(PLA-b-PDMAEMA-b
      PEtOxMA) star-like block copolymers in aqueous media was investigated by
      dissipative particle dynamics (DPD) to explore the formation process of
      unimolecular micelles. The simulation results showed that using longer
      hydrophobic or pH-sensitive chains, shorter hydrophilic backbones, smaller
      hydrophilic side chain grafting density, and fewer polymer arms resulted in
      micellar aggregation. Furthermore, this unimolecular polymeric micelle could be
      used for encapsulating gold nanoparticles, whose mesoscopic structure was also
      explored. The gold nanoparticles tended to distribute in the middle layer formed
      by PDMAEMA, and the unimolecular micelles were capable of impeding gold
      nanoparticle aggregation. This study could help understand the formation
      mechanism of unimolecular micelles formed from star-like block copolymers in
      dilute solutions and offer a theoretical guide to the design and preparation of
      promising unimolecular polymeric micelles with targeting properties.

PMID- 27711541
TI  - Electron transfer across the germanium-polyelectrolyte-gold nanoparticle
      interface: convenient detection and applications in sensing.
AB  - Germanium-polyelectrolyte-gold nanoparticle composites were prepared and
      characterized using FTIR-ATR spectroscopy and scanning electron microscopy. The
      germanium (Ge) element served as an internal reflection element and the buildup
      of the layered system was followed in situ. A positively charged polyelectrolyte,
      poly (allylamine hydrochloride) (PAH) adsorbs spontaneously on negatively charged
      Ge. Citrate-stabilized gold nanoparticles can then be adsorbed onto the PAH
      layer. Upon illumination of the device with visible light a prominent absorption
      over the entire mid infrared region is observed which is due to intervalence band
      transitions in Ge. The strong infrared signals are evidence for holes in the
      valence band of the Ge semiconductor, which arise due to electron transfer to the
      gold nanoparticles (GNPs). The electron transfer, as evidenced by the holes in
      Ge, is affected by the nature of the gap between the Ge semiconductor and the
      GNPs. Increasing the gap by adsorbing polyelectrolyte multilayers hinders the
      electron transfer. Also, heating and vacuum have a pronounced effect. The device
      is proposed as a sensor, where the sensing event is transduced into an optical
      signal in the infrared region, as demonstrated for a thiol molecule. The thiol
      has a large affinity for gold, and therefore affects the germanium-gold
      nanoparticle gap. This reduces the electron transfer, and therefore the
      absorption in the infrared region upon illumination with visible light. Removal
      of the thiol from the solution leads to the recovery of the signal.

PMID- 27711542
TI  - Bottom-up excited state dynamics of two cinnamate-based sunscreen filter
      molecules.
AB  - Methyl-E-4-methoxycinnamate (E-MMC) is a model chromophore of the commonly used
      commercial sunscreen agent, 2-ethylhexyl-E-4-methoxycinnamate (E-EHMC). In an
      effort to garner a molecular-level understanding of the photoprotection
      mechanisms in operation with E-EHMC, we have used time-resolved pump-probe
      spectroscopy to explore E-MMC's and E-EHMC's excited state dynamics upon UV-B
      photoexcitation to the S1 (11pipi*) state in both the gas- and solution-phase. In
      the gas-phase, our studies suggest that the excited state dynamics are driven by
      non-radiative decay from the 11pipi* to the S3 (11npi*) state, followed by de
      excitation from the 11npi* to the ground electronic state (S0). Using both a non
      polar-aprotic solvent, cyclohexane, and a polar-protic solvent, methanol, we
      investigated E-MMC and E-EHMC's photochemistry in a more realistic, 'closer-to
      shelf' environment. A stark change to the excited state dynamics in the gas-phase
      is observed in the solution-phase suggesting that the dynamics are now driven by
      efficient E/Z isomerisation from the initially photoexcited 11pipi* state to S0.

PMID- 27711543
TI  - Exploring the substrate specificity and catalytic mechanism of
      imidazolonepropionase (HutI) from Bacillus subtilis.
AB  - Imidazolonepropionase (HutI, EC 3.5.2.7) catalyzes the hydrolytic cleavage of
      carbon-nitrogen bond in 4-imidazolone-5-propionic acid (IPA) to yield l
      formiminoglutamic acid, which is the third step in the universal histidine
      degradation pathway. In this article, using a combined quantum mechanics and
      molecular mechanics (QM/MM) approach, the specificity and catalytic mechanism of
      HutI from Bacillus subtilis have been explored by considering the four isomers of
      (S)- and (R)-enantiomers of IPA (SIPA-1, SIPA-2, RIPA-1 and RIPA-2). Our
      calculations reveal that the activation of hydrolytic water (a zinc-bound water)
      is performed by residue E252 via a "bridging" water molecule, which occurs before
      binding of the substrate. After the substrate binding, this activation channel is
      blocked by the substrate, and the other two residues (D324 and H272) cannot act
      as the general base to activate the hydrolytic water. For the two (S)-enantiomers
      of IPA, HutI can specifically convert one isomer of (S)-enantiomer (SIPA-1) to l
      formiminoglutamic acid with an energy barrier of 16.6 kcal mol-1. The conversion
      of another (S)-enantiomer (SIPA-2) corresponds to the energy barrier of 21.9 kcal
      mol-1. However, for the two isomers of (R)-enantiomer, RIPA-1 corresponds to a
      higher energy barrier (21.8 kcal mol-1), and RIPA-2 is associated with a weak
      binding in the active site compared to SIPA-2. Thus, on the basis of our
      calculations, SIPA-1 is suggested to be the most favorable substrate for HutI,
      whereas the hydrolytic cleavage of SIPA-2 may require a preliminary isomerization
      to SIPA-1.

PMID- 27711545
TI  - Adsorption in zeolites using mechanically embedded ONIOM clusters.
AB  - We have explored mechanically embedded three-layer QM/QM/MM ONIOM models for
      computational studies of binding in Al-substituted zeolites. In all the models
      considered, the high-level-theory layer consists of the adsorbate molecule and of
      the framework atoms within the first two coordination spheres of the Al atom and
      is treated at the M06-2X/6-311G(2df,p) level. For simplicity, flexibility and
      routine applicability, the outer, low-level-theory layer is treated with the UFF.
      We have modelled the intermediate-level layer quantum mechanically and
      investigated the performance of HF theory and of three DFT functionals, B3LYP,
      M06-2X and omegaB97x-D, for different layer sizes and various basis sets, with
      and without BSSE corrections. We have studied the binding of sixteen probe
      molecules in H-MFI and compared the computed adsorption enthalpies with published
      experimental data. We have demonstrated that HF and B3LYP are inadequate for the
      description of the interactions between the probe molecules and the framework
      surrounding the metal site of the zeolite on account of their inability to
      capture dispersion forces. Both M06-2X and omegaB97x-D on average converge within
      ca. 10% of the experimental values. We have further demonstrated transferability
      of the approach by computing the binding enthalpies of n-alkanes (C1-C8) in H
      MFI, H-BEA and H-FAU, with very satisfactory agreement with experiment. The
      computed entropies of adsorption of n-alkanes in H-MFI are also found to be in
      good agreement with experimental data. Finally, we compare with published
      adsorption energies calculated by periodic-DFT for n-C3 to n-C6 alkanes, water
      and methanol in H-ZSM-5 and find very good agreement.

PMID- 27711546
TI  - Morphological modulation of graphene-mediated hybridization in plasmonic systems.
AB  - We investigated the plasmonic response of a 2-dimensional ordered array of
      closely spaced (few-nm apart) Au nanoparticles covered by a large-area single
      layer graphene sheet. The array consisted of coherently aligned nanoparticle
      chains, endowed with a characteristic uniaxial anisotropy. The joint effect of
      such a morphology and of the very small particle size and spacing led to a
      corresponding uniaxial wrinkling of graphene in the absence of detectable strain.
      The deposition of graphene redshifted the Au plasmon-resonance, strongly
      increased the optical absorption of the array and, most importantly, induced a
      marked optical anisotropy in the plasmonic response, absent in the pristine
      nanoparticle array. The experimental observations are accounted for by invoking a
      graphene-mediated resistive coupling between the Au nanoparticles, where the
      optical anisotropy arises from the wrinkling-induced anisotropic electron
      mobility in graphene at optical frequencies.

PMID- 27711547
TI  - A computational study of the competing reaction mechanisms of the photo-catalytic
      reduction of CO2 on anatase(101).
AB  - We perform a computational study of three different reaction mechanisms for the
      photo-catalytic reduction of CO2 on the TiO2 anatase(101) surface known as (i)
      the carbene, (ii) the formaldehyde and (iii) the glyoxal pathways. We define a
      set of approximations that allows testing a number of mechanistic hypotheses and
      design experiments to validate them. We find that the energetically most
      favourable reaction mechanism among those proposed in the literature is the
      formaldehyde path, and the rate-limiting step is likely to be the formation of
      CH3 radicals from dissociation of CH3OH. We show that an intermediate that
      supports this mechanism is OCH2OH. We also find that formaldehyde would be an
      energetically favorable intermediate forming from CO and HCO, intermediates that
      are proposed in the early stage of the carbene and glyoxal pathways respectively.
      Some possible variants of mechanisms and methods to ease the formation of CH3
      radicals are also discussed.

PMID- 27711548
TI  - Superelastic stress-strain behavior in ferrogels with different types of magneto
      elastic coupling.
AB  - Colloidal magnetic particles embedded in an elastic polymer matrix constitute a
      smart material called a ferrogel. It responds to an applied external magnetic
      field by changes in elastic properties, which can be exploited for various
      applications such as dampers, vibration absorbers, or actuators. Under
      appropriate conditions, the stress-strain behavior of a ferrogel can display a
      fascinating feature: superelasticity, the capability to reversibly deform by a
      huge amount while barely altering the applied load. In previous work, using
      numerical simulations, we investigated this behavior assuming that the magnetic
      moments carried by the embedded particles can freely reorient to minimize their
      magnetic interaction energy. Here, we extend the analysis to ferrogels where
      restoring torques by the surrounding matrix hinder rotations towards a
      magnetically favored configuration. For example, the particles can be chemically
      cross-linked into the polymer matrix and the magnetic moments can be fixed to the
      particle axes. We demonstrate that these systems still feature a superelastic
      regime. As before, the nonlinear stress-strain behavior can be reversibly
      tailored during operation by external magnetic fields. Yet, the different
      coupling of the magnetic moments causes different types of response to external
      stimuli. For instance, an external magnetic field applied parallel to the
      stretching axis hardly affects the superelastic regime but stiffens the system
      beyond it. Other smart materials featuring superelasticity, e.g. metallic shape
      memory alloys, have already found widespread applications. Our soft polymer
      systems offer many additional advantages such as a typically higher deformability
      and enhanced biocompatibility combined with high tunability.

PMID- 27711549
TI  - The unfolding effects on the protein hydration shell and partial molar volume: a
      computational study.
AB  - In this paper we apply the computational analysis recently proposed by our group
      to characterize the solvation properties of a native protein in aqueous solution,
      and to four model aqueous solutions of globular proteins in their unfolded states
      thus characterizing the protein unfolded state hydration shell and quantitatively
      evaluating the protein unfolded state partial molar volumes. Moreover, by using
      both the native and unfolded protein partial molar volumes, we obtain the
      corresponding variations (unfolding partial molar volumes) to be compared with
      the available experimental estimates. We also reconstruct the temperature and
      pressure dependence of the unfolding partial molar volume of Myoglobin dissecting
      the structural and hydration effects involved in the process.

PMID- 27711550
TI  - Magnetomigration of rare-earth ions in inhomogeneous magnetic fields.
AB  - The effects of external inhomogenous (gradient) magnetic fields on the movement
      of the rare-earth ions: Dy3+, Gd3+ and Y3+, in initially homogeneous aqueous
      solutions have been investigated. Differences in the migration of rare-earth ions
      in gradient magnetic fields were observed, depending on the magnetic character of
      the ions: paramagnetic ions of Dy3+ and Gd3+ move towards regions of the sample
      where the magnetic field gradient is the strongest, while diamagnetic ions of Y3+
      move in the opposite direction. It has been showed that the low magnetic field
      gradients, such the ones generated by permanent magnets, are sufficient to
      observe the magnetomigration effects of the ions in solution. The present work
      clearly establishes the behavior of magnetically different ions in initially
      homogeneous aqueous solutions exposed to magnetic field gradients. To this avail,
      a methodology for measuring the local concentration differences of metal ions in
      liquid samples was developed.

PMID- 27711551
TI  - Strong 1D localization and highly anisotropic electron-hole masses in heavy
      halogen functionalized graphenes.
AB  - While halogenation of graphene presents a fascinating avenue to the construction
      of a chemically and physically diverse class of systems, their application in
      photovoltaics has been hindered by often prohibitively large optical gaps. Herein
      we study the effects of partial bromination and chlorination on the structure and
      optoelectronic properties of both graphane and fluorographene. We find brominated
      and chlorinated fluorographene derivatives to be as stable as graphane with a
      detailed investigation of the systems band structure revealing significant 1D
      localization of the charge carriers as well as strongly electron-hole asymmetric
      effective masses. Lastly using G0W0 and BSE, we investigate the optical
      adsorption spectra of the aforementioned materials whose first adsorption peak is
      shown to lie close to the optimal peak position for photovoltaic applications
      (~1.5 eV).

PMID- 27711552
TI  - Conformation-specific spectroscopy of capped, gas-phase Aib oligomers: tests of
      the Aib residue as a 310-helix former.
AB  - The conformational preferences of a series of capped peptides containing the
      helicogenic amino acid aminoisobutyric acid (Aib) (Z-Aib-OH, Z-(Aib)2-OMe, and Z
      (Aib)4-OMe) are studied in the gas phase under expansion-cooled conditions. Aib
      oligomers are known to form 310-helical secondary structures in solution and in
      the solid phase. However, in the gas phase, accumulation of a macrodipole as the
      helix grows could inhibit helix stabilization. Implementing single-conformation
      IR spectroscopy in the NH stretch region, Z-Aib-OH and Z-(Aib)2-OMe are both
      observed to have minor conformations that exhibit dihedral angles consistent with
      the 310-helical portion of the Ramachandran map (phi, psi = -57 degrees , -30
      degrees ), even though they lack sufficient backbone length to form 10-membered
      rings which are a hallmark of the developed 310-helix. For Z-(Aib)4-OMe three
      conformers are observed in the gas phase. Single-conformation infrared
      spectroscopy in both the NH stretch (Amide A) and C[double bond, length as m
      dash]O stretch (Amide I) regions identifies the main conformer as an incipient
      310-helix, having two free NH groups and two C10 H-bonded NH groups, labeled an F
      F-10-10 structure, with a calculated dipole moment of 13.7 D. A second minor
      conformer has an infrared spectrum characteristic of an F-F-10-7 structure in
      which the third and fourth Aib residues have phi, psi = 75 degrees , -74 degrees 
      and -52 degrees , 143 degrees , Ramachandran angles which fall outside of the
      typical range for 310-helices, and a dipole moment that shrinks to 5.4 D. These
      results show Aib to be a 310-helix former in the gas phase at the earliest stages
      of oligomer growth.

PMID- 27711554
TI  - Hysteresis phenomenon in a reaction system of nanocrystalline iron and a mixture
      of ammonia and hydrogen.
AB  - During nitriding of nanocrystalline iron and reduction of iron nitrides with
      NH3/H2 mixtures, at the stationary states a hysteresis phenomenon is observed
      where two phases coexist, according to the extended phase rule of Gibbs due to
      the presence of an additional degree of freedom associated with the size of the
      nanocrystallites. Nanocrystallites transform from the biggest ones to the
      smallest due to differences in energy demand.

PMID- 27711553
TI  - Dichlorophosphanyl isocyanate - spectroscopy, conformation and molecular
      structure in the gas phase and the solid state.
AB  - Dichlorophosphanyl isocyanate, Cl2PNCO, was synthesized and characterized by IR,
      Raman and 31P NMR spectroscopy. The conformational properties and molecular
      structures were studied by using gas electron diffraction (GED), X-ray
      crystallography and quantum-chemical calculations. Extensive DFT and ab initio
      calculations show that the potential energy surface of Cl2PNCO upon rotating the
      P-N bond is rather flat; three conformers, namely syn, anti and gauche between
      the NCO group and the bisector of the ClPCl angle, were theoretically predicted.
      Experimentally, only one conformer was indicated by gas-phase IR spectroscopy and
      the preference for a gauche conformation in both gas phase and solid state was
      unambiguously ascertained by gas electron diffraction and X-ray crystallographic
      data. In the solid state, the Cl2PNCO molecules adopt a gauche conformation with
      two distinct dihedral angles Cl-P-N-C of -121.3(2) and 137.4(2) degrees  and form
      polymeric chains through weak intermolecular CO contacts. Additionally, the
      dynamic character of the position of the isocyanate group of Cl2PNCO was examined
      in the gas phase.

PMID- 27711555
TI  - Na-ion diffusion in a NASICON-type solid electrolyte: a density functional study.
AB  - Based on density functional theory, we have systematically studied the crystal
      and electronic structures, and the diffusion mechanism of the NASICON-type solid
      electrolyte Na3Zr2Si2PO12. Four possible elementary processes are addressed:
      three inner-chain and one inter-chain processes. In inner-chain processes, Na
      tends to move inside the Na diffusion chain, while Na moves across the Na
      diffusion chain in the inter-chain process. The activation energies for the inner
      chain and inter-chain processes are 230 meV and 260 meV, respectively. By
      combining possible elementary processes, three preferable pathways along a, b,
      and c directions are found.

PMID- 27711556
TI  - Switching adsorption and growth behavior of ultrathin [C2C1Im][OTf] films on
      Au(111) by Pd deposition.
AB  - Combining in vacuo deposition of ultrathin ionic liquid (UTIL) films with angle
      resolved X-ray photoelectron spectroscopy (ARXPS), we demonstrate that by
      deposition of submonolayer amounts of Pd onto Au(111) the initial growth mode of
      the ionic liquid (IL) 1-ethyl-3-methylimidazolium trifluoromethanesulfonate
      ([C2C1Im][OTf]) can be switched from three-dimensional (3D) to two-dimensional
      (2D) growth, that is, from non-wetting to wetting. On clean Au(111), pronounced
      3D growth occurs on top of an initially formed 2D wetting layer with cations and
      anions next to each other in a checkerboard arrangement. After pre- or
      postdeposition of only 0.7 ML Pd, two-dimensional layer-by-layer growth is found,
      which is attributed to strong attractive interactions between [C2C1Im][OTf] and
      surface Pd. For Pd post deposition onto the IL, the ARXPS data revealed
      particularly strong interactions between the dialkylimidazolium cation and Pd
      atoms, which considerably reduce the regular surface alloying of Pd with the Au
      substrate stabilizing Pd at the metal surface. In the context of heterogeneous
      catalysis using the SCILL (solid catalyst coated with ionic liquid layer)
      concept, these results directly provide a possible explanation on the molecular
      level for the beneficial influence of the IL layer in case of heterogeneous metal
      alloy catalysts.

PMID- 27711557
TI  - Theoretical characterization of the conformational features of unnatural
      oligonucleotides containing a six nucleotide genetic alphabet.
AB  - The addition of the unnatural P:Z base pair to the four naturally occurring DNA
      bases expands the genetic alphabet and yields an artificially expanded genetic
      information system (AEGIS). Herein, the structural feature of oligonucleotides
      containing a novel unnatural P:Z base pair is characterized using both molecular
      dynamics and quantum chemistry. The results show that the incorporation of the
      novel artificial base pair (P:Z) preserves the global conformational feature of
      duplex DNA except for some local structures. The Z-nitro group imparts new
      properties to the groove width, which widens the major groove. The unnatural
      oligonucleotides containing mismatched base pairs exhibit low stability. This
      ensures efficient and high-fidelity replication. In general, the incorporation of
      the P:Z pair strengthens the stability of the corresponding DNA duplex. The
      calculated results also show that the thermostability originates from both
      hydrogen interaction and stacking interaction. The Z-nitro group plays an
      important role in enhancing the stability of the H-bonds and stacking strength of
      the P:Z pair. Overall, the present results provide theoretical insights in the
      exploration of artificially expanded genetic information systems.

PMID- 27711558
TI  - Molecular origin of photoluminescence of carbon dots: aggregation-induced orange
      red emission.
AB  - The molecular origin of the photoluminescence of carbon dots (CDs) is not known.
      This restricts the design of CDs with desired optical properties. We have
      synthesized CDs starting from carbohydrates by employing a simple synthesis
      method. We were able to demonstrate that the CDs are composed of aggregated
      hydroxymethylfurfural (HMF) derivatives. The optical properties of these CDs are
      quite unique. These CDs exhibit an excitation-independent PL emission maximum in
      the orange-red region (lambda ~ 590 nm). These CDs also exhibit excitation as
      well as monitoring wavelength-independent single exponential PL decay. These
      observations indicate that only one type of chromophore (HMF derivative) is
      present within the CDs. Several HMF derivatives are aggregated within the CDs;
      therefore, the aggregated structure cause a large Stokes shift (~150 nm). By
      several control experiments, we showed that the same aggregated chromophore unit
      (HMF derivative), and not the individual fluorophores, is the fluorescing unit.
      The emission maximum and the single exponential PL lifetime are independent of
      the polarity of the medium. The existence of a low-lying trap state could be
      reduced quite significantly. A model has been proposed to explain the interesting
      steady state and dynamical photoluminescence behaviour of the CDs. As the
      molecular origin of their photoluminescence is known, CDs with desired optical
      properties can be designed.

PMID- 27711559
TI  - Conductive multi-walled boron nitride nanotubes by catalytic etching using cobalt
      oxide.
AB  - Boron nitride nanotubes (BNNTs) are ceramic compounds which are hardly oxidized
      below 1000  degrees C due to their superior thermal stability. Also, they are
      electrically almost insulators with a large band gap of 5 eV. Thus, it is a
      challenging task to etch BNNTs at low temperature and to convert their electrical
      properties to a conductive behavior. In this study, we demonstrate that BNNTs can
      be easily etched at low temperature by catalytic oxidation, resulting in an
      electrically conductive behavior. For this, multi-walled BNNTs (MWBNNTs)
      impregnated with Co precursor (Co(NO3)2.6H2O) were simply heated at 350  degrees
      C under air atmosphere. As a result, diverse shapes of etched structures such as
      pits and thinned walls were created on the surface of MWBNNTs without losing the
      tubular structure. The original crystallinity was still kept in the etched
      MWBNNTs in spite of oxidation. In the electrical measurement, MWBNNTs with a
      large band gap were converted to electrical conductors after etching by catalytic
      oxidation. Theoretical calculations indicated that a new energy state in the gap
      and a Fermi level shift contributed to MWBNNTs being conductive.

PMID- 27711560
TI  - The effect of halide and iodate anions on the hydrogen-bonding network of water
      in aqueous nanodrops.
AB  - The hydration of halide and iodate anions was investigated using electrospray
      ionization (ESI) mass spectrometry and infrared photodissociation (IRPD)
      spectroscopy. The average cluster sizes, determined from the abundances of X
      (H2O)n (X- = F-, Cl-, Br-, I-, IO3-) in the ESI mass spectra, follow the order F-
      > IO3- ~ Cl- > Br- > I-. The average cluster sizes and solution hydration
      enthalpies of the halides increase linearly with decreasing ionic radii, but IO3-
      does not fit this trend. The correlation between average cluster sizes and
      solution hydration enthalpies indicates that there is a similar relationship
      between ion-water interactions in these large gas-phase clusters and in bulk
      solution. The abundances of odd number clusters between n = 49 and 55 for I-, Br-
      and Cl- are enhanced but those for F- and IO3- are not. I- and IO3- have nearly
      the same ionic radii, but evidence suggests that these ions interact with water
      molecules differently both in solution and in small clusters. IRPD spectra of I
      (H2O)n and IO3-(H2O)n, measured for select cluster sizes between n = 30 and 75
      reveal differences in the hydrogen-bonding network of water molecules in these
      two ions even for sizes around n = 50. This indicates that differences in
      hydration motifs reported previously for the first hydration shells of I- and IO3
      propagate to water molecules past the second solvation shell, a phenomenon that
      has not been reported previously for singly charged anions.

PMID- 27711562
TI  - Incorporating QM and solvation into docking for applications to GPCR targets.
AB  - A great number of GPCR crystal structures have been solved in recent years,
      enabling GPCR-targeted drug discovery using structure-based approaches such as
      docking. GPCRs generally have wide and open entrances to the binding sites, which
      render the binding sites readily accessible to solvent. GPCRs are also populated
      with hydrophilic residues in the extracellular regions. Thus, including solvent
      and polarization effects can be important for accurate GPCR docking. To test this
      hypothesis, a new docking protocol which incorporates quantum
      mechanical/molecular mechanical (QM/MM) calculations along with an implicit
      solvent model is developed. The new docking method treats the ligands and the
      protein residues in the binding sites as QM regions and performs QM/MM
      calculations with implicit solvent. The results of a test on all solved GPCR
      cocrystals show a significant improvement over the conventional docking method.

PMID- 27711561
TI  - Evidence of spin-temperature in dynamic nuclear polarization: an exact
      computation of the EPR spectrum.
AB  - In dynamic nuclear polarization (DNP) experiments, the compound is driven out-of
      equilibrium by the microwave (MW) irradiation of the radical electron spins.
      Their stationary state has been recently probed via electron double resonance
      (ELDOR) techniques showing, at low temperature, a broad depolarization of the
      electron paramagnetic resonance (EPR) spectrum under microwave irradiation. In
      this theoretical manuscript, we develop a numerical method to compute exactly the
      EPR spectrum in the presence of dipolar interactions. Our results reproduce the
      observed broad depolarisation and provide a microscopic justification for the
      spectral diffusion mechanism. We show the validity of the spin-temperature
      approach for typical radical concentration used in dissolution DNP protocols. In
      particular once the interactions are properly taken into account, the spin
      temperature is consistent with the non-monotonic behavior of the EPR spectrum
      with a wide minimum around the irradiated frequency.

PMID- 27711563
TI  - Preparation and electrochemical properties of Li2MoO3/C composites for
      rechargeable Li-ion batteries.
AB  - Layered Li2MoO3 is a potential candidate for a high-capacity positive electrode
      material for Li-ion batteries because of its excess lithium composition. However,
      the difficulty of single-phase preparation and its insulating nature are
      drawbacks for its application in lithium-ion batteries. A small quantity of
      acetylene black added in the starting material solves these drawbacks, i.e. the
      formation of impurity phases and the low conductivity. As a result, a Li2MoO3/C
      composite is successfully synthesized with the simple addition of acetylene
      black. Since the electronic conductivity of the composite is enhanced to more
      than 1000 times higher than that of bare Li2MoO3, the Li2MoO3/C composite
      delivers approximately 230 mA h g-1 of initial discharge capacity in a voltage
      range of 1.5-4.3 V, while carbon-free Li2MoO3 shows only 110 mA h g-1 of initial
      discharge capacity. During the initial lithium extraction and insertion, a
      partial transformation from a layered into a cation-disordered cubic structure is
      evidenced in the Li2MoO3/C composite electrode by X-ray diffraction.

PMID- 27711564
TI  - The i-TTM model for ab initio-based ion-water interaction potentials. II. Alkali
      metal ion-water potential energy functions.
AB  - A new set of i-TTM potential energy functions describing the interactions between
      alkali metal ions and water molecules is reported. Following our previous study
      on halide ion-water interactions [J. Phys. Chem. B, 2016, 120, 1822], the new i
      TTM potentials are derived from fits to CCSD(T) reference energies and, by
      construction, are compatible with the MB-pol many-body potential, which has been
      shown to accurately predict the properties of water from the gas to the condensed
      phase. Within the i-TTM formalism, two-body repulsion, electrostatic, and
      dispersion energies are treated explicitly, while many-body effects are
      represented by classical induction. The accuracy of the new i-TTM potentials is
      assessed through extensive comparisons with results obtained from different ab
      initio methods, including CCSD(T), CCSD(T)-F12b, DF-MP2, and several DFT models,
      as well as from polarizable force fields for M+(H2O)n clusters with M+ = Li+,
      Na+, K+, Rb+, and Cs+, and n = 1-4.

PMID- 27711565
TI  - Understanding the effect of an in situ generated and integrated spinel phase on a
      layered Li-rich cathode material using a non-stoichiometric strategy.
AB  - Recently, spinel-layered integrated Li-rich cathode materials have attracted
      great interest due to the large enhancement of their electrochemical
      performances. However, the modification mechanism and the effect of the
      integrated spinel phase on Li-rich layered cathode materials are still not very
      clear. Herein, we have successfully synthesized the spinel-layered integrated Li
      rich cathode material using a facile non-stoichiometric strategy (NS-LNCMO). The
      rate capability (84 mA h g-1vs. 28 mA h g-1, 10 C), cycling stability (92.4% vs.
      80.5%, 0.2 C), low temperature electrochemical capability (96.5 mA h g-1vs. 59 mA
      h g-1, -20  degrees C), initial coulomb efficiency (92% vs. 79%) and voltage
      fading (2.77 V vs. 3.02 V, 200 cycles@1 C) of spinel-layered integrated Li-rich
      cathode materials have been significantly improved compared with a pure Li-rich
      phase cathode. Some new insights into the effect of the integrated spinel phase
      on a layered Li-rich cathode have been proposed through a comparison of the
      structure evolution of the integrated and Li-rich only materials before and after
      cycling. The Li-ion diffusion coefficient of NS-LNCMO has been enlarged by about
      3 times and almost does not change even after 100 cycles indicating an enhanced
      structure stability. The integration of the spinel phase not only enhances the
      structure stability of the layered Li-rich phase during charging-discharging but
      also expands the interslab spacing of the Li-ion diffusion layer, and elongates
      TM-O covalent bond lengths, which lowers the activation barrier of Li+
      transportation, and alleviates the structure strain during the cycling procedure.

PMID- 27711566
TI  - Light-induced charge separation in a P3HT/PC70BM composite as studied by out-of
      phase electron spin echo spectroscopy.
AB  - A composite material of semiconducting polymer P3HT and fullerene derivative
      PC70BM was studied by means of electron spin echo (ESE) spectroscopy. The out-of
      phase ESE signal was observed under laser irradiation of the composite at low
      temperature. We assume that during the charge separation process firstly the spin
      correlated radical pairs in the singlet-polarized spin state are formed, and then
      the net polarization of radical pairs arises due to spin evolution. Both types of
      polarizations contribute to the out-of-phase ESE signal in the case of non-ideal
      microwave pulses. Analytical calculation of the echo shape for both types of
      initial polarization revealed that the contribution of the net polarization
      becomes zero after averaging over the whole EPR spectrum of the radical pair.
      This behavior was experimentally confirmed; thus the analysis of the out-of-phase
      ESE signal was simplified. Interspin distance distributions in the charge
      transfer state were obtained by modeling the out-of-phase ESE envelope modulation
      measured at different delays after laser flash TDAF from 300 ns to 3.3 MUs at a
      temperature of 65 K. Due to geminate recombination and diffusion of the radicals
      from the interface the distribution becomes significantly broader with larger
      distances prevailing at longer TDAF values. The average distance between charges
      increases from 3.5 nm to 5.6 nm with an increase in TDAF.

PMID- 27711567
TI  - Design and simple synthesis of composite Bi12TiO20/Bi4Ti3O12 with a good
      photocatalytic quantum efficiency and high production of photo-generated hydroxyl
      radicals.
AB  - Hybrid Bi12TiO20/Bi4Ti3O12 composites with different Bi : Ti molar ratios were
      successfully fabricated using a one-step solid-state calcination. These samples
      were characterized using X-ray diffraction, specific surface area analysis,
      scanning electron microscopy, high-resolution microscopy, selected-area electron
      diffraction, X-ray photoelectron spectroscopy, UV-vis diffuse reflection
      spectroscopy, photoluminescence analyses, and photocurrent and electrochemical
      impedance spectroscopy. Some specified techniques were also used to investigate
      the photocatalytic properties and the formation of radical species under UV-vis
      irradiation. The composites provide an efficient pathway for photo-produced
      electrons and holes to diffuse and transfer to the exterior of the particles for
      photodegradation, because of the good contact between hybrid Bi12TiO20 and
      Bi4Ti3O12. Therefore, the hybrid Bi12TiO20/Bi4Ti3O12 can prolong the carrier
      lifetime as compared to any individual material (Bi12TiO20 or Bi4Ti3O12). In
      particular, the hybrid Bi12TiO20/Bi4Ti3O12 composite with a Bi : Ti ratio of 12 :
      6 had the longest photo-generated carrier lifetime and produced the maximum
      amount of hydroxyl radicals during UV-vis irradiation; therefore, it demonstrated
      the best photo-catalytic properties. A Z-scheme mechanism was proposed to explain
      the hydroxyl radical yield and photodegradation.

PMID- 27711568
TI  - Generation of highly reactive oxygen species on metal-supported MgO(100) thin
      films.
AB  - The formation of highly reactive oxygen species (ROS) on metal oxide surfaces has
      attracted considerable interest due to their diverse applications. In this work,
      we have performed density functional theory calculations to investigate the co
      adsorption of oxygen and water on ultrathin MgO(100) films deposited on a Mo(100)
      substrate. We reveal that molecular oxygen can be completely decomposed stepwise
      with the assistance of water. Consequently, a series of highly ROS including
      superoxide, hydroperoxide, hydroxyl and single oxygen adatoms are formed on
      Mo(100) supported MgO(100) thin films. The reaction barriers accompanied by the
      generation of ROS are reported, and the influence of the thickness of MgO(100)
      films is also discussed. The promising routes to produce these species provide
      valuable information to understand the importance of synergy effects between the
      substrate, the co-adsorbed species, and the film thickness in multiphase catalyst
      design.

PMID- 27711569
TI  - Excited-state relaxation of the solar cell dye D49 in organic solvents and on
      mesoporous Al2O3 and TiO2 thin films.
AB  - We present an ultrafast UV-Vis-NIR transient absorption study of the donor
      acceptor solar-cell dye D49 in diisopropyl ether, THF and acetonitrile, as well
      as on mesoporous Al2O3 and TiO2 thin films. Photoexcitation at 505 nm initially
      populates the first electronically excited state of the dye having significant
      intramolecular charge transfer character ("S1/ICT"). On Al2O3 and in the three
      organic solvents, the dynamics are fully explained in terms of S1/ICT
      stabilisation (by reorientation of adjacent solvent or D49 molecules and
      collisional cooling), intramolecular vibrational redistribution and S1/ICT -> S0
      electronic decay. A substantial decrease of the S1/ICT lifetime is observed with
      increasing polarity of the surrounding medium suggesting an acceleration of
      internal conversion. In agreement with these results, the addition of the
      nonpolar co-adsorbent deoxycholic acid (DCA) to the Al2O3 surface leads to a
      substantial increase of the S1/ICT lifetime. DCA spacers reduce the local
      polarity around the dye molecules, thus interrupting D49 "self-solvation". These
      results are in contrast to a recent experimental study for the indoline dye D131
      on Al2O3, where charge transfer from electronically excited D131 to adjacent dye
      molecules was proposed (Cappel et al., Sci. Rep., 2016, 6, 21276). We do not see
      evidence for charge transfer processes between D49 molecules and also not for
      electron injection from D49 into Al2O3 trap states. Charge separation is only
      observed for D49 bound to TiO2 thin films, with efficient injection of electrons
      into the conduction band of the semiconductor via formation of a [D49+e-] complex
      and a transient Stark effect signalling the formation of mobile electrons upon
      dissociation of the complex.

PMID- 27711570
TI  - Probing the microhydration of metal carbonyls: a photoelectron velocity-map
      imaging spectroscopic and theoretical study of Ni(CO)3(H2O)n.
AB  - A series of microhydrated nickel carbonyls, Ni(CO)3(H2O)n- (n = 0-4), are
      prepared via a laser vaporization supersonic cluster source in the gas phase and
      identified by mass-selected photoelectron velocity-map imaging spectroscopy and
      quantum chemical calculations. Vertical detachment energies for the n = 1-4
      anions are measured from the photoelectron spectra to be 1.429 +/- 0.103, 1.698
      +/- 0.090, 1.887 +/- 0.080, and 2.023 +/- 0.074 eV, respectively. The C-O
      stretching vibrational frequencies in the corresponding neutral clusters are
      determined to be 1968, 1950, 1945, and 1940 cm-1 for n = 1-4, respectively, which
      are characteristic of terminal CO. It is determined that the hydrogen atom of the
      first water molecule is bound to the nickel center. Addition of a second water
      molecule prefers solvation at the carbonyl terminal. Spectroscopy combined with
      theory suggests that the solvation of nickel tricarbonyl is dominated by a water
      ring network. The present findings would have important implications for the
      fundamental understanding of the multifaceted mechanisms of the multibody
      interaction of water and carbon monoxide with transition metals.

PMID- 27711571
TI  - Kinetics of prebiotic depsipeptide formation from the ester-amide exchange
      reaction.
AB  - In this work, we introduce a kinetic model to study the effectiveness of ester
      mediated amide bond formation under prebiotic conditions. In our previous work,
      we found that a simple system composed of alpha-hydroxy acids and alpha-amino
      acids is capable of forming peptide bonds via esterification followed by the
      ester-amide exchange reaction. To further understand the kinetic behavior of this
      copolymerization, we first tracked the growth of initial species from a
      valine/lactic acid mixture in a closed system reactor. A mathematical model was
      developed to simulate the reactions and evaluate the rate constants at different
      temperatures. We found these reactions can be described by the empirical
      Arrhenius equation even when reaction occurred in the solid (dry) state. Further
      calculations for activation parameters showed that the ester-mediated pathway
      facilitates amide bond formation by lowering activation entropies. These results
      provide a theoretical framework that illustrates why the ester-mediated pathway
      for peptide bond formation is efficient and why it would have been more favorable
      on the early Earth, compared to peptide bond formation without the aid of hydroxy
      acids.

PMID- 27711572
TI  - Influence of asymmetric depletion of solvents on the electric double layer of
      charged objects in binary polar solvent mixtures.
AB  - For binary solvent mixtures composed of ions and two kinds of polar solvents, the
      electric double layer near a charged object is strongly affected by not only the
      binary solvent composition but also the nature of the solvents, such as the
      volume and dipole moment of the solvent molecule. Accounting for the difference
      in sizes of solvents and the orientational ordering of solvent dipoles, we
      theoretically obtain general expressions for the spatial distribution functions
      of solvents and ions, in planar geometry and within the mean-field approach.
      While focusing on long-range electrostatic interaction and neglecting short-range
      interactions such as preferential solvation, our approach predicts an asymmetric
      depletion of the two solvents from the charged surface and a behavior of
      decreased permittivity of the binary solvent mixture. Furthermore, we suggest
      that the key factor for the depletion is the ratio of the solvent dipole moment
      to the solvent volume. The influence of the binary solvent composition, the
      volume of solvent and the dipole moment of the solvent on the number density of
      solvents, the permittivity and the differential capacitance is presented and
      discussed. We conclude that accounting for the difference in the volume and
      dipole moment between polar solvents is necessary for a new approach to represent
      more realistic situations such as preferential solvation.

PMID- 27711573
TI  - A comparative study of small 3d-metal oxide (FeO)n, (CoO)n, and (NiO)n clusters.
AB  - Geometrical and electronic structures of the 3d-metal oxide clusters (FeO)n,
      (CoO)n, and (NiO)n are computed using density functional theory with the
      generalized gradient approximation in the range of 1 <= n <= 10. It is found that
      the cluster geometries are similar in the (FeO)n and (CoO)n series but noticeably
      different in the (NiO)n series for several values of n. All of the lowest total
      energy states are found to possess relatively small spin multiplicities and are
      either antiferromagnetic or ferrimagnetic except for the states of (NiO)3,
      (NiO)4, (NiO)9, and (NiO)10, which are ferromagnetic. The computed
      polarizabilities per atom undergo a steep decrease when compared to the atomic
      values of the MO monomers (M = Fe, Co, and Ni). Surprisingly, the polarizability
      does not strongly depend on either M or n in all the considered series when n
      varies from 3 to 10. The binding energies per atom are the largest in the (FeO)n
      series, followed by the binding energies of (CoO)n and (NiO)n.

PMID- 27711574
TI  - Classification of hydrogen bond flips in small water polyhedra applied to
      concerted proton tunneling.
AB  - Recently a new mechanism of proton tunneling in a prism-like water hexamer was
      revealed [Richardson et al., Science, 2016, 351, 1310]. The tunneling motion
      involves the concerted breaking of two hydrogen bonds and rotations of two
      nearest water molecules. Eventually, this structural transformation means
      flipping one of the hydrogen bonds without the creation of defects in the
      hydrogen bond network. On the surface of polyhedral water clusters, there are
      five essentially different types of hydrogen bonds, and only two of them can be
      changed in this manner. In this article, the topological classification of such
      transformations for five small water polyhedra: triangular, pentagonal, and
      hexagonal prisms as well as cube and polyhedron 4454, consisting of four square
      and four pentagonal faces, is presented. Our classification includes the
      enumeration of all possible one-bond-flips with consideration of the types of
      hydrogen bonds on the polyhedral surface. Attention is paid to the most stable
      proton configurations which can be studied in experiments. It was established
      that a number of one-bond-flip transitions between the low energy configurations
      are possible in clusters in the shape of triangular and pentagonal prisms.

PMID- 27711575
TI  - Understanding the role of silica nanospheres with their light scattering and
      energy barrier properties in enhancing the photovoltaic performance of ZnO based
      solar cells.
AB  - The present study discusses the design and development of a dye sensitized solar
      cell (DSSC) using a hybrid composite of ZnO nanoparticles (ZnO NP) and silica
      nanospheres (SiO2 NS). A ~22% enhancement in the overall power conversion
      efficiency (PCE, eta) was observed for the device fabricated with a binary hybrid
      composite of 1 wt% SiO2 NS and ZnO NP compared to the pristine ZnO NP device. A
      systematic investigation revealed the dual function of the silica nanospheres in
      enhancing the device efficacy compared to the bare ZnO NP based device. Sub
      micron sized SiO2 NS can boost the light harvesting efficiency of the photoanode
      by optical confinement, resulting in increased propagation length of the incident
      light by multiple internal reflections, which was confirmed by UV-Vis diffused
      reflectance spectroscopy. Electrochemical impedance spectroscopic (EIS) analysis
      showed a reduced recombination of photo-generated electrons to the I-/I3- redox
      shuttle in the case of the composite photoanode. The higher recombination
      resistance (Rct) in the case of a 1 wt% composite indicates that the SiO2 NS
      serves as a partial energy barrier layer to retard the interfacial recombination
      (back transfer) of photo-generated electrons at the working electrode/electrolyte
      interface, increasing the device efficiency.

PMID- 27711576
TI  - Dynamics of silver ions in AgI doped Ag2O-SeO2-MoO3 mixed former glasses.
AB  - We have studied the dynamics of silver ions in AgI-doped Ag2O-SeO2-MoO3 mixed
      former glasses in wide frequency and temperature ranges. We have observed that
      the ionic conductivity exhibits a mixed glass network former effect for low AgI
      content. The scaling for the conductivity spectra shows that the mechanism of
      charge carrier dynamics is independent of temperature and composition. We have
      obtained a mobile Ag+ ion concentration from the Nernst-Einstein relation, which
      is found to be independent of temperature, but slightly dependent on composition.
      We have also obtained the characteristic mean square displacement of the silver
      ions from the mapping of the conductivity spectra in the time domain. It is
      observed that the composition dependence of the characteristic displacement is
      opposite to that of the conductivity. We have also studied the influence of the
      network structure of these glasses on ion dynamics using infrared spectra and
      established a correlation between the ion dynamics and the SeO32- structural
      units. It is observed that the available hopping sites for Ag+ ions increase in
      the glass network with the increase of non-bridging oxygens of SeO32- units.

PMID- 27711577
TI  - Enhanced low-temperature ionic conductivity via different Li+ solvated clusters
      in organic solvent/ionic liquid mixed electrolytes.
AB  - We investigate Li+ coordination in mixed electrolytes based on ionic liquids
      (ILs) and organic solvents and its relation with the macroscopic properties such
      as phase behaviour and ionic conductivity. Using Raman spectroscopy we determine
      the solvation shell around Li+ in mixtures formed by the IL N-butyl-N
      methylpyrrolidinium bis(trifluoromethanesulfonyl)imide, the organic solvents
      ethylene carbonate and dimethyl carbonate (EC : DMC 1 : 1), and the salt LiTFSI.
      We find that the organic solvent molecules preferentially solvate Li+ as long as
      there are enough of them. Our results are consistent with a model where
      Li(EC)3(DMC)1 and Li(EC)2(DMC)2 are the main complexes formed by the organic
      solvent molecules and where TFSI- mainly participates in Li(TFSI)2- clusters. As
      the amount of organic solvent is increased, the number of TFSI- around Li+
      rapidly decreases showing a higher affinity of the organic solvents to solvate
      Li+. The changes in the local configurations are also reflected in the ionic
      conductivity and the phase behaviour. The formation of larger clusters leads to a
      decrease in the conductivity, whereas the presence of several different clusters
      at intermediate compositions effectively hinders crystallization at low
      temperatures. The result is an enhanced low-temperature ionic conductivity in
      comparison with the pure IL or organic solvent electrolytes.

PMID- 27711578
TI  - NaGdF4:Dy3+ nanofibers and nanobelts: facile construction technique, structure
      and bifunctionality of luminescence and enhanced paramagnetic performances.
AB  - Luminescent-magnetic bifunctional NaGdF4:Dy3+ nanofibers and nanobelts have been
      successfully fabricated by a combination of electrospinning followed by
      subsequent calcination with fluorination technology for the first time. The
      structure, morphologies, and luminescence and magnetic properties of the
      synthesized materials have been investigated by a variety of techniques. X-ray
      diffraction (XRD) analysis shows that as-prepared NaGdF4:Dy3+ nanostructures are
      pure hexagonal structures. Scanning electron microscopy (SEM) observations
      indicate that directly electrospinning-made PVP/[NaNO3 + Gd(NO3)3 + Dy(NO3)3]
      composite nanofibers and nanobelts have smooth surfaces, good dispersion and
      uniform size, and surfaces of NaGdF4:Dy3+ nanofibers and nanobelts become rough
      after calcination and fluorination processes. The mean diameters of PVP/[NaNO3 +
      Gd(NO3)3 + Dy(NO3)3] composite nanofibers and NaGdF4:0.5%Dy3+ nanofibers are,
      respectively, 402.20 +/- 2.39 nm and 246.06 +/- 5.84 nm at the confidence level
      of 95%. The mean widths and thicknesses of PVP/[NaNO3 + Gd(NO3)3 + Dy(NO3)3]
      composite nanobelts and NaGdF4:0.5%Dy3+ nanobelts are 4.16 +/- 0.17 MUm and 279
      nm, and 0.83 +/- 0.01 MUm and 130 nm, respectively. Under the excitation of 274
      nm ultraviolet light, NaGdF4:Dy3+ nanofibers and nanobelts show the predominant
      blue and yellow emission peaks at 478 and 570 nm corresponding to the 4F9/2 ->
      6HJ/2 (J = 15, 13) energy level transitions of Dy3+ ions, respectively.
      NaGdF4:0.5%Dy3+ nanofibers have higher photoluminescence intensity than their
      nanobelt counterpart. In addition, all the NaGdF4:Dy3+ nanofibers and nanobelts
      display superparamagnetic properties. The NaGdF4:0.5%Dy3+ nanobelts show the
      highest magnetization, and NaGdF4:0.5%Dy3+ nanofibers have slightly higher
      magnetization values than NaGdF4 nanofibers. NaGdF4:Dy3+ nanofibers and nanobelts
      simultaneously possess excellent luminescence and enhanced superparamagnetic
      properties, which make them ideally suitable for application in many fields such
      as solid-state lasers, lighting and displays, and magnetic resonance imaging. The
      design conception and construction strategy developed in this work may provide
      some new guidance for the synthesis of other rare earth fluoride nanostructures
      with various morphologies.

PMID- 27711579
TI  - An experimental and theoretical study on the electronic and structural properties
      of CdSe@TiO2 nanotube arrays.
AB  - In this work, the effects of the structural (crystallite size, stress) and
      electronic parameters (band gap, lifetime) on the photoelectrocatalysis and
      electron transport over CdSe electrodeposited inside TiO2-nanotubes (CdSe@TiO2NT)
      were investigated. Density functional theory (DFT) calculations of TiO2 were used
      to elucidate the electronic band structure and to correlate with experimental
      values. CdSe was grown by pulsed electrodeposition into previous and late thermal
      treated TiO2NT (Sample-PTT and Sample-LTT, respectively) without blocking the
      nanotube's entrance. The Rietveld refinement method was used to obtain
      information from crystallographic data of each photoelectrode. The lattice
      strains calculated from the Rietveld analysis for Sample-PTT and Sample-LTT were
      0.472 and 0.540, and the average volume of the TiO2-anatase unit cell increased
      from 133.235(0) A3 to 136.950(6) A3, respectively. Sample-PTT exhibited higher
      experimental electron lifetime, larger than 1.0 order of magnitude compared to
      Sample-LTT photoanodes. The band structures and DOS obtained by computational
      modelling showed theoretical band gap values of 2.54 eV and 2.75 eV, which were
      close to the experimental values. All studies evidenced a strong dependence of
      the electronic properties of the CdSe@TiO2 samples on their morphology, and,
      consequently, on their photoelectrochemical activity in water splitting.

PMID- 27711580
TI  - Hydrogenated borophene as a stable two-dimensional Dirac material with an
      ultrahigh Fermi velocity.
AB  - The recent synthesis of monolayer borophene (triangular boron monolayer) on a
      substrate has opened the era of boron nanosheets (Science, 2015, 350, 1513), but
      the structural instability and a need to explore the novel physical properties
      are still open issues. Here we demonstrated that borophene can be stabilized by
      full surface hydrogenation (borophane), from first-principles calculations. Most
      interestingly, our calculations show that borophane has direction-dependent Dirac
      cones, which are mainly caused by the in-plane px and py orbitals of boron atoms.
      The Dirac fermions possess an ultrahigh Fermi velocity of up to 3.5 * 106 m s-1
      under the HSE06 level, which is 4 times higher than that of graphene. The Young's
      moduli are calculated to be 190 and 120 GPa nm along two different directions,
      which are comparable to those of steel. The ultrahigh Fermi velocity and good
      mechanical features render borophane ideal for nanoelectronic applications.

PMID- 27711581
TI  - In situ Raman investigation of electrolyte solutions in the vicinity of graphite
      negative electrodes.
AB  - The structure of electrolyte solutions plays an important role in the lithium-ion
      intercalation reaction at graphite negative electrodes. The solvation structure
      of an electrolyte solution in bulk has been investigated previously. However, the
      structure of an electrolyte solution at the graphite negative
      electrode/electrolyte solution interface, where the lithium-ion intercalation
      reaction occurs is more important. In this study, the structure of electrolyte
      solutions in the vicinity of a graphite negative electrode was investigated using
      in situ Raman spectroscopy during the 1st reduction process in 1 mol dm-3
      LiClO4/ethylene carbonate (EC) + diethyl carbonate (DEC) (1 : 1 volume ratio), 1
      mol dm-3 LiCF3SO3/propylene carbonate (PC), and 1 mol dm-3 LiCF3SO3/PC +
      tetraethylene glycol dimethyl ether (tetraglyme) (20 : 1 volume ratio). As a
      result, in the electrolyte solutions in which the lithium-ion intercalation
      reaction can occur (LiClO4/EC + DEC and LiCF3SO3/PC + tetraglyme), the Raman
      spectra of free solvent molecules (EC or PC) and anions showed a positive
      vibrational frequency shift during the co-intercalation reaction, and these
      shifts returned to their original positions during the lithium-ion intercalation
      reaction. On the other hand, there is no vibrational frequency shift in
      LiCF3SO3/PC, an electrolyte in which the lithium-ion intercalation reaction
      cannot occur. Based on our results, the relationship between the Raman shift and
      the solid electrolyte interphase (SEI) formation process was discussed.

PMID- 27711582
TI  - Evidence for dissolved hydrogen in the mixed ionic-electronic conducting
      perovskites La0.6Sr0.4FeO3-delta and SrTi0.7Fe0.3O3-delta.
AB  - Two mixed ionic-electronic conducting, Fe-containing perovskites were
      investigated regarding their reducibility in dry H2, namely lanthanum strontium
      ferrite (LSF4, La0.6Sr0.4FeO3-delta) and strontium titanium ferrite (STF3,
      SrTi0.7Fe0.3O3-delta). Upon treatment under comparable reduction conditions, LSF4
      is by far more affected by reduction and is reduced more deeply than STF3.
      Thermal treatments of fully oxidized or slightly reduced LSF4/STF3 at decreased
      O2 partial pressure lead to spontaneous desorption of O2. Temperature-programmed
      desorption (TPD) spectra of H2 reveal distinct differences in H2 and H2O
      desorption. A simple mass balance of H2 reveals that oxygen vacancies formed on
      STF3 are more resilient towards O2 re-oxidation compared to those on LSF4. The
      results also imply that substantial amounts of hydrogen are dissolved in the bulk
      of LSF4 or STF3. 4.9 * 10-2 mol H2 per mol LSF4 and 1.6 * 10-2 mol H2 per mol
      STF3 are incorporated if the specimens are heated in flowing/dry H2 up to 550 
      degrees C and 612  degrees C, respectively. For LSF4 this equals about 13
      hypothetical ML of H2 and for STF3 about 20 hypothetical ML of H2. This
      conclusion is also supported by Fourier-transform infrared spectroscopy (FT-IR).
      FT-IR reveals water formation during static H2 treatment of LSF4/STF3, which
      indicates perovskite reduction. Furthermore, both samples behave extraordinarily
      hydrophobic and no chemistry involving surface hydroxy groups was observed.

PMID- 27711583
TI  - Magnetic behavior of superatomic-fullerene assemblies.
AB  - It has recently been possible to synthesize ordered assemblies composed of
      magnetic superatomic clusters Ni9Te6(PEt3)8 separated by C60 and study their
      magnetic behavior. We have carried out theoretical studies on model systems
      consisting of magnetic superatoms separated by non-magnetic species to examine
      the evolution in magnetic response as the nature of the magnetic superatom
      (directions of spin quantization), the strength of isotropic and anisotropic
      interactions, the magnetic anisotropy energy, and the size of the assembly are
      varied. We have examined square planar configurations consisting of 16, 24 and 48
      sites with 8, 12 and 24 magnetic superatoms respectively. The magnetic atoms are
      allowed 2 or 5 orientations. The model Hamiltonian includes isotropic exchange
      interactions with second nearest neighbor ferromagnetic and nearest neighbor
      antiferromagnetic couplings and anisotropic Dzyaloshinskii-Moriya interactions.
      It is shown that the inclusion of Dzyaloshinskii-Moriya interaction that cause
      spin canting is necessary to get qualitative response as observed in experiments.

PMID- 27711584
TI  - Emission in Gd6O5F8:Yb3+,Er3+ micro-particles for multimodal luminescence and
      temperature sensing upon 980 nm excitation.
AB  - Mono-dispersed Gd6O5F8:Yb3+/Er3+ micro-particles with different doping
      concentrations (Er3+: 0.1-1%) were synthesized by a facile hydrothermal route.
      The emission spectra, luminescent dynamic power-dependence and temperature
      sensing of up-conversion photoluminescence were investigated in detail. Under 980
      nm excitation, the as-prepared samples exhibit intense red up-conversion and NIR
      emissions, which are influenced by the doping concentrations of Er3+ within
      Gd6O5F8. With increasing concentrations of Er3+ ions, the visible up-conversion
      emissions first increase and then decrease, but NIR down-conversion emissions
      display a distinct trend, in which one peak at 1010 nm is highly suppressed and
      another at 1530 nm is increased quickly. Furthermore, the 980 nm excited optical
      temperature sensing property of the synthesized sample is realized over a wide
      temperature range by monitoring the intensity of up-conversion luminescence. The
      study provides a novel strategy based on lanthanide oxy-fluoride micro-particles
      for multifunctional displays, lighting and temperature sensing in a single
      system.

PMID- 27711585
TI  - Rational selection of amorphous or crystalline V2O5 cathode for sodium-ion
      batteries.
AB  - Vanadium oxide (V2O5), as a potential positive electrode for sodium ion batteries
      (SIBs), has attracted considerable attention from researchers. Herein, amorphous
      and crystalline V2O5 cathodes on a graphite paper without a binder and conductive
      additives have been synthesized via facile anodic electrochemical deposition
      following different heat treatments. Both the amorphous V2O5 (a-V2O5) cathode and
      crystalline V2O5 (c-V2O5) cathode show good rate cycling performance and long
      cycling life. After five rate cycles, the reversible capacities of both the
      cathodes were almost unchanged at different current densities from 40 to 5120 mA
      g-1. Long cycling tests with 10 000 cycles were carried out and the two cathodes
      exhibit excellent cycling stability. The c-V2O5 cathode retains a high specific
      capacity of 54 mA h g-1 after 10 000 cycles at 2560 mA g-1 and can be charged
      within 80 s. Interestingly, the a-V2O5 cathode possesses higher reversible
      capacities than the c-V2O5 cathode at low current densities, whereas it is
      inversed at high current densities. The c-V2O5 cathode shows faster capacity
      recovery from 5120 to 40 mA g-1 than the a-V2O5 cathode. When discharged at 80 mA
      g-1 (long discharge time of 140 min) and charged at 640 mA g-1 (short charge time
      of 17 min), the a-V2O5 cathode shows a higher discharge capacity than its c-V2O5
      counterpart. The different electrochemical performance of a-V2O5 and c-V2O5
      cathodes during various electrochemical processes can provide a rational
      selection of amorphous or crystalline V2O5 cathode materials for SIBs in their
      practical applications to meet the variable requirements.

PMID- 27711586
TI  - Charge-transfer and isomerization reactions of trans-4-(N-arylamino)stilbenes.
AB  - We studied the excited-state dynamics of trans-4-(N-arylamino)stilbenes with aryl
      = phenyl (p1H), 4-methoxyphenyl (p1OM), or 4-cyanophenyl (p1CN) in solvents of
      varied polarity and viscosity by using femtosecond transient absorption and time
      correlated single photon counting techniques. In nonpolar solvents the decay is
      triexponential, in which the rapid component corresponds to vibrational cooling
      combined with solvation, the intermediate temporal component 41-120 ps to trans
      cis isomerization, and the long one ~1 ns to fluorescence decay of the S1 state.
      The S1 state has a delocalized geometry and charge-transfer characteristics,
      corresponding to a planar intramolecular charge transfer (PICT) state. In polar
      solvents, an excited-state absorption band appears near 520 and 480 nm for p1OM
      and p1CN, respectively but not for p1H. This band has a rise lifetime of 4.3/7.5,
      16.3/9.4, and 29.5/16 ps for p1CN/p1OM in acetonitrile (ACN), dimethylformamide
      (DMF), and dimethyl sulfoxide (DMSO), respectively and matches the decay of the
      600 nm PICT band. This band is thus assigned to the absorption of a singlet
      twisted intramolecular charge transfer state (TICT). The conversion rate
      decreases as the solvent viscosity is increased and is consistent with a large
      structural variation amplitude. Theoretical calculations using density functional
      theory (DFT), method PEB0, were employed to obtain the optimized structures and
      energies of those states. The PICT state possesses delocalized pi electrons along
      the molecule. The TICT for p1CN is formed by twisting about the aminostilbene
      benzonitrile C-N bond by ~90 degrees , but it is about the stilbene-aniline C-N
      bond for p1OM. We observed faster conversion rates for p1CN in alcoholic
      solvents, in which the lifetimes for both the PICT and TICT states are shortened
      to 20-99 ps and 120-660 ps, respectively, as a result of solvent-solute H-bonding
      interactions. In p1OM, the TICT state has an elongated C[double bond, length as m
      dash]C bond in the stilbene moiety, which might facilitate the trans-cis
      isomerization reaction and thus account for the relatively short lifetime of 58
      420 ps in polar solvents.

PMID- 27711587
TI  - Towards understanding the kinetic behaviour and limitations in photo-induced
      copper(i) catalyzed azide-alkyne cycloaddition (CuAAC) reactions.
AB  - The kinetic behaviour of the photo-induced copper(i) catalyzed azide-alkyne
      cycloaddition (CuAAC) reaction was studied in detail using real-time Fourier
      transform infrared (FTIR) spectroscopy on both a solvent-based monofunctional and
      a neat polymer network forming system. The results in the solvent-based system
      showed near first-order kinetics on copper and photoinitiator concentrations up
      to a threshold value in which the kinetics switch to zeroth-order. This kinetic
      shift shows that the photo-CuAAC reaction is not susceptible from side reactions
      such as copper disproportionation, copper(i) reduction, and radical termination
      at the early stages of the reaction. The overall reaction rate and conversion is
      highly dependent on the initial concentrations of photoinitiator and copper(ii)
      as well as their relative ratios. The conversion was decreased when an excess of
      photoinitiator was utilized compared to its threshold value. Interestingly, the
      reaction showed an induction period at relatively low intensities. The induction
      period is decreased by increasing light intensity and photoinitiator
      concentration. The reaction trends and limitations were further observed in a
      solventless polymer network forming system, exhibiting a similar copper and
      photoinitiator threshold behaviour.

PMID- 27711588
TI  - Coalescence behavior of liquid immiscible metal drops in two-wall confinement.
AB  - Molecular dynamics (MD) simulations are performed to investigate the coalescence
      of the liquid Al and Pb drops in the graphene (G) walls and pillared-graphene
      (PG) walls. The confining walls can affect the coalescence dynamics of two
      adjacent films by restricting the movement of one of the metal drops; however,
      the coalescence behavior is different in the G-walls and the PG-walls. Two un
      contacted films can still merge into one bigger drop because of the restricting
      effect of the walls, in which the movement of the Pb drop plays a predominant
      role. The coalescence time decreases with the decrease of the confining space.
      Our findings demonstrate that the coalescence dynamics can be controlled by
      tuning the confining space or wall surface.

PMID- 27711589
TI  - Multivalent bonds in self-assembled bundles of ultrathin gold nanowires.
AB  - Ultrathin gold nanowires are unusual colloidal objects that assemble into bundles
      with line contacts between parallel wires. Each molecule in the contact line
      interacts with many ligand and solvent molecules. We used X-ray scattering and
      electron microscopy to study how these interactions control assembly.

PMID- 27711590
TI  - pH-Responsive drug release and NIR-triggered singlet oxygen generation based on a
      multifunctional core-shell-shell structure.
AB  - A multifunctional platform with pH-responsive drug release and near-infrared
      (NIR) light-triggered photodynamic therapy (PDT) was designed and prepared using
      the novel core-shell-shell structure. The multifunctional platform consists of an
      upconversion nanoparticle (UCNP) emission core, a photosensitizer methylene blue
      (MB) embedded dense silica sandwich shell, and a polyethyleneimine conjugated
      folic acid (PEI-FA) gated mesoporous silica (MS) outmost shell with doxorubicin
      hydrochloride (DOX) loaded inside. The simulated drug release experiments
      revealed that DOX will release from the nanoparticles because of the distortion
      in the PEI-FA layer under acidic conditions. Moreover, under 980 nm NIR
      irradiation, a 660 nm red light emission was excited, activating MB to generate a
      singlet oxygen (1O2), which acts as the PDT drug. The multifunctional platform
      integrated pH-responsive drug release and UCNP-based PDT drug together show
      promising potential in nanomedicine for future chemotherapy and NIR-triggered
      PDT.

PMID- 27711591
TI  - Black-box determination of temperature-dependent susceptibilities for crystalline
      organic radicals with complex magnetic topologies.
AB  - In all but the simplest crystal structures, the identification of all relevant
      interactions between magnetic sites as well as the setup of magnetic model
      spaces, which are necessary for modeling macroscopic magnetism, are tedious and
      error-prone tasks. Here, we present a procedure to generate magnetic
      susceptibility versus temperature curves using only a crystal structure as input.
      The procedure, which is based on the first-principles bottom-up approach [Deumal
      et al., J. Phys. Chem. A, 2002, 106, 1299], is designed in a way to require as
      little user interference as possible. We employ quantum chemical calculations to
      parametrize a Heisenberg Hamiltonian, which is set up and diagonalized for
      different magnetic model spaces to ensure convergence of the model. We apply the
      procedure to several 6-oxo-verdazyl radical structures, including newly
      synthesized compounds, and compare the results to data we obtained from magnetic
      susceptibility measurements as well as published data to further benchmark our
      procedure. Furthermore, the different impact of certain dominating coupling
      constants is systematically analyzed.

PMID- 27711592
TI  - Cation-cation and anion-anion complexes stabilized by halogen bonds.
AB  - Stable minima showing halogen bonds between charged molecules with the same sign
      have been explored by means of theoretical calculations. The dissociation
      transition states and their corresponding barriers have also been characterized.
      In all cases, the results indicate that the complexes are thermodynamically
      unstable but kinetically stable with respect to the isolated monomers in gas
      phase. A corrected binding energy profile by removing the charge-charge repulsion
      of the monomers shows a profile similar to the one observed for the dissociation
      of analogous neutral systems. The nature of the interaction in the minima and TSs
      has been analyzed using the symmetry adapted perturbation theory (SAPT) method.
      The results indicate the presence of local favorable electrostatic interactions
      in the minima that vanish in the TSs. Natural bond orbital (NBO) and "atoms-in
      molecules" (AIM) theories were used to analyze the complexes, obtaining good
      correlations between Laplacian and electron density values with both bond
      distances and charge-transfer energy contributions E(2). The largest E(2) orbital
      interaction energies for cation-cation and anion-anion complexes are 561.2 and
      197.9 kJ mol-1, respectively.

PMID- 27711593
TI  - Multifunctional heterostructures constructed using MoS2 and WS2 nanoribbons.
AB  - Using first-principles calculations based on nonequilibrium Green's function
      together with density functional theory, we investigated the electronic transport
      properties of some devices consisting of armchair and zigzag MoS2NRs/WS2NRs in
      plane heterostructures. The results indicate that these heterostructures exhibit
      rectifying performance, which are depressed as the number of WS2NR unit cell
      decreases. In addition, the NDR effect is observed and can be modulated.
      Importantly, the zigzag MoS2NRs/WS2NRs heterostructures can be used as spintronic
      devices because of their tunable spin filtering behavior and NDR effect. The
      devices with WS2NRs electrode display a better NDR effect and spin filtering
      behavior. The unique properties of these heterostructures suggest promising
      applications in the next generation nanoelectronic devices.

PMID- 27711594
TI  - Vapour adsorption kinetics: statistical rate theory and zeta adsorption isotherm
      approach.
AB  - The equilibrium zeta adsorption isotherm for vapours indicates the amount
      adsorbed is finite for vapour-phase pressures approaching the saturation value,
      and is strongly supported by experimental measurements for a number of different
      vapour-solid surface systems. This isotherm assumes the adsorbate consists of
      differently sized molecular clusters in local equilibrium rather than the
      adsorbate being in layers. We use the local-equilibrium approximation and develop
      a method to determine the expression for chemical potential of the adsorbate in
      terms of the amount adsorbed, nA(t). This allows us to apply statistical rate
      theory to calculate nA(t) at five different vapour-phase pressures, xV
      (=PV/Psat), in terms of a parameter, re. Statistical rate theory indicates that
      re describes the dynamics of a given isolated system under equilibrium
      conditions. We consider two methods for determining the value of re that give the
      best agreement with the measurements performed at each of five values of xV. In
      one method, we assume, re, is a function of both temperature, T, and pressure,
      xV, and determine the five best-fit values of re. In the experiments, xV changes
      by a factor of more than two, but the standard deviation in the re values is 6%.
      In the second method, we assume re is a function only of T; and find that the
      value of re is not changed significantly. In all cases, the calculated nA(t)
      agree with the measurements.

PMID- 27711595
TI  - Density functional simulation of resonant inelastic X-ray scattering experiments
      in liquids: acetonitrile.
AB  - In this paper we report an experimental and computational study of liquid
      acetonitrile (H3C-C[triple bond, length as m-dash]N) by resonant inelastic X-ray
      scattering (RIXS) at the N K-edge. The experimental spectra exhibit clear
      signatures of the electronic structure of the valence states at the N site and
      incident-beam-polarization dependence is observed as well. Moreover, we find fine
      structure in the quasielastic line that is assigned to finite scattering duration
      and nuclear relaxation. We present a simple and light-to-evaluate model for the
      RIXS maps and analyze the experimental data using this model combined with ab
      initio molecular dynamics simulations. In addition to polarization-dependence and
      scattering-duration effects, we pinpoint the effects of different types of
      chemical bonding to the RIXS spectrum and conclude that the H2C-C[double bond,
      length as m-dash]NH isomer, suggested in the literature, does not exist in
      detectable quantities. We study solution effects on the scattering spectra with
      simulations in liquid and in vacuum. The presented model for RIXS proved to be
      light enough to allow phase-space-sampling and still accurate enough for
      identification of transition lines in physical chemistry research by RIXS.

PMID- 27711596
TI  - Aliphatic-aromatic stacking interactions in cyclohexane-benzene are stronger than
      aromatic-aromatic interaction in the benzene dimer.
AB  - Stacking interactions between cyclohexane and benzene were studied in crystal
      structures from the Cambridge Structural Database and by ab initio calculations.
      Calculated at the very accurate CCSD(T)/CBS level of theory, the cyclohexane
      benzene interaction energy is -3.27 kcal mol-1, which is significantly stronger
      than the interaction in the benzene dimer (-2.84 kcal mol-1) indicating the
      importance of aliphatic-aromatic interactions.

PMID- 27711597
TI  - Coronene-based metal-organic framework: a theoretical exploration.
AB  - With the help of first-principle calculations we have proposed a new 2D metal
      organic framework (MOF) consisting of a -NH substituted coronene molecule and
      transition metals. Our study reveals that formation of such crystals is
      exothermic in nature, i.e. it is an energetically favourable process. The mode of
      magnetic coupling between the local magnetic moments and hence the overall
      magnetic moment of the MOF can be tuned by changing the transition metal. Not
      only the magnetic properties, but also the electronic structure of the MOF can be
      regulated from half-metal to spin-semiconductor to semimetallic-semiconductor by
      altering the metal center from Cr to Mn to Fe/Co. Our study also indicates that
      the change in the ligand structure and its anchoring group is also very effective
      in tuning the electronic properties of MOFs. The study of transport properties
      reveals that the half-metallic crystal possesses the maximum value of the spin
      filtering efficiency, i.e. 100%.

PMID- 27711599
TI  - Bidirectional particle transport and size selective sorting of Brownian particles
      in a flashing spatially periodic energy landscape.
AB  - We demonstrate a size sensitive experimental scheme which enables bidirectional
      transport and fractionation of paramagnetic colloids in a fluid medium. It is
      shown that two types of magnetic colloidal particles with different sizes can be
      simultaneously transported in opposite directions, when deposited above a stripe
      patterned ferrite garnet film subjected to a square-wave magnetic modulation. Due
      to their different sizes, the particles are located at distinct elevations above
      the surface, and they experience two different energy landscapes, generated by
      the modulated magnetic substrate. By combining theoretical arguments and
      numerical simulations, we reveal such energy landscapes, which fully explain the
      bidirectional transport mechanism. The proposed technique does not require pre
      imposed channel geometries such as in conventional microfluidics or lab-on-a-chip
      systems, and permits remote control over the particle motion, speed and
      trajectory, by using relatively low intense magnetic fields.

PMID- 27711598
TI  - Viscometry of single nanoliter-volume droplets using dynamic force spectroscopy.
AB  - The viscometry of minute amounts of liquid has been in high demand as a novel
      tool for medical diagnosis and biological assays. Various microrheological
      techniques have shown the capability to handle small volumes. However, as the
      liquid volume decreases down to nanoliter scale, increasingly dominant surface
      effects complicate the measurement and analysis, which remain a challenge in
      microrheology. Here, we demonstrate an atomic force microscope-based platform
      that determines the viscosity of single sessile drops of 1 nanoliter Newtonian
      fluids. We circumvent interfacial effects by measuring the negative-valued shear
      elasticity, originating from the retarded fluidic response inside the drop. Our
      measurement is independent of the liquid-boundary effects, and thus is valid
      without a priori knowledge of surface tension or contact angle, and consistently
      holds at a 1 milliliter-scale volume. Importantly, while previous methods
      typically need a much larger 'unrecoverable' volume above 1 microliter, our
      simple platform uses only ~1 nanoliter. Our results offer a quantitative and
      unambiguous methodology for viscosity measurements of extremely minute volumes of
      Newtonian liquids on the nanoliter scale.

PMID- 27711600
TI  - Solvothermal synthesis, stirring-assisted assembly and photoelectric performance
      of Te nanowires.
AB  - Tellurium nanowires (NWs) are attractive one-dimensional materials for many
      applications, yet most synthesis processes require hazardous chemical reducing
      agents and extreme operating conditions. Here we described a solvothermal
      synthesis of Te NWs using a non-toxic reducing agent, ascorbic acid. Then the Te
      NWs were assembled into a well-aligned film through a stirring-assisted oil-water
      air interface assembly method and a Te NWs photodetector was fabricated which is
      sensitive to infrared radiation. The photodetector based on the well-aligned Te
      NWs film had a series of more excellent photoelectric properties than that based
      on those being randomly oriented. For example, the photoresponsivity of the
      former is 103 times larger, and the response time is 1.15 * 103 times shorter,
      than those of the latter.

PMID- 27711601
TI  - Low energy electron catalyst: the electronic origin of catalytic strategies.
AB  - Using a low energy electron (LEE) as a catalyst, the electronic origin of the
      catalytic strategies corresponding to substrate selectivity, reaction specificity
      and reaction rate enhancement is investigated for a reversible unimolecular
      elementary reaction. An electronic energy complementarity between the catalyst
      and the substrate molecule is the origin of substrate selectivity and reaction
      specificity. The electronic energy complementarity is induced by tuning the
      electronic energy of the catalyst. The energy complementarity maximizes the
      binding forces between the catalyst and the molecule. Consequently, a new
      electronically metastable high-energy reactant state and a corresponding new low
      barrier reaction path are resonantly created for a specific reaction of the
      substrate through the formation of a catalyst-substrate transient adduct. The LEE
      catalysis also reveals a fundamental structure-energy correspondence in the
      formation of the catalyst-substrate transient adduct. Since the energy
      complementarities corresponding to the substrate molecules of the forward and the
      backward steps of the reversible reactions are not the same due to their
      structural differences, the LEE catalyst exhibits a unique one-way catalytic
      strategy, i.e., the LEE catalyst favors the reversible reaction more effectively
      in one direction. A characteristic stronger binding of the catalyst to the
      transition state of the reaction than in the initial reactant state and the final
      product state is the molecular origin of barrier lowering.

PMID- 27711603
TI  - The influence of mass-transport conditions on the ethanol oxidation reaction
      (EOR) mechanism of Pt/C electrocatalysts.
AB  - This study aims to provide further understanding of the influence of different
      parameters that control mass-transport (the revolution rate of the rotating disk
      electrode and the potential scan rate) on the ethanol oxidation reaction (EOR).
      The experiments were conducted on a home-made carbon-supported 20 wt% Pt/C
      electrocatalyst, synthesized using a modified polyol method, and characterized in
      terms of physicochemical properties by thermogravimetric analysis (TGA), powder X
      ray diffraction (XRD) and transmission electron microscopy (TEM). The EOR at the
      thin active layer of this electrocatalyst was characterized using both
      differential electrochemical mass spectrometry (DEMS) in a flow cell
      configuration and the rotating disc electrode (RDE). The results demonstrate that
      operating under stationary conditions (low scan rate and high RDE speed) hinders
      complete ethanol electrooxidation into CO2 and favors the poisoning of the
      electrocatalyst surface by hydroxide and strong ethanol adsorbates. As such, the
      EOR appears to be more efficient and faster under dynamic conditions than in near
      steady-state.

PMID- 27711602
TI  - Nuclear spin hyperpolarization with ansa-aminoboranes: a metal-free perspective
      for parahydrogen-induced polarization.
AB  - The parahydrogen-induced polarization (PHIP) phenomenon, observed when
      parahydrogen is used in H2 addition processes, provides a means for substantial
      NMR signal enhancements and mechanistic studies of chemical reactions. Commonly,
      noble metal complexes are used for parahydrogen activation, whereas metal-free
      activation is rare. Herein, we report a series of unimolecular metal-free
      frustrated Lewis pairs based on an ansa-aminoborane (AAB) moiety in the context
      of PHIP. These molecules, which have a "molecular tweezers" structure, differ in
      their substituents at the boryl site (-H, -Ph, -o-iPr-Ph, and -Mes). PHIP effects
      were observed for all the AABs after exposing their solutions to parahydrogen in
      a wide temperature range, and experimental measurements of their kinetic and
      thermodynamic parameters were performed. A theoretical analysis of their nuclear
      spin polarization effects is presented, and the roles of chemical exchange,
      chemical equilibrium and spin dynamics are discussed in terms of the key
      dimensionless parameters. The analysis allowed us to formulate the prerequisites
      for achieving strong polarization effects with AAB molecules, which can be
      applied for further design of efficient metal-free tweezers-like molecules for
      PHIP. Mechanistic (chemical and physical) aspects of the observed effects are
      discussed in detail. In addition, we performed quantum chemical calculations,
      which confirmed that the J-coupling between the parahydrogen-originated protons
      in AAB-H2 molecules is mediated through dihydrogen bonding.

PMID- 27711604
TI  - Bifurcated dissociative photoionization mechanism of acetic acid anhydride
      revealed by imaging photoelectron photoion coincidence spectroscopy.
AB  - The fragmentation processes of internal energy selected acetic acid anhydride
      cations, Ac2O+, were investigated by imaging photoelectron photoion coincidence
      (iPEPICO) spectroscopy. The first dissociation channel leads to the formation of
      CH3C(O)OCO+ (m/z = 87) by a CH3-loss. The 0 K appearance energy (E0) was
      determined to be 10.289 +/- 0.010 eV, in excellent agreement with the G4
      calculated 10.28 eV transition state (TS) energy. Based on the thermochemical
      onset of CH3C(O)OCO+, a reverse barrier of 40 kJ mol-1 was found. The second
      dissociation channel leads to the formation of the acetyl cation, CH3CO+ (m/z =
      43). The appearance of trace amounts of acetone in the mass spectra, statistical
      modeling of the branching ratios, and quantum chemical calculations point to the
      existence of a post-transition-state bifurcation on the potential energy surface
      and a single TS leading to multiple products. That is, at higher excess energies,
      the CH3-group may swerve back along an orbiting pathway to form the acetone
      cation by CO2-loss instead of leaving directly. The acetone cation thus formed is
      then energetic enough to lose a methyl group and yield the acetyl cation at a
      phenomenological E0 = 10.316 +/- 0.015 eV. The acetyl cation, which dominates the
      breakdown diagram up to 16 eV photon energy, is also formed by sequential CO2
      loss from the CH3C(O)OCO+ intermediate at E0 = 10.53 +/- 0.03 eV. The CH3+ (m/z =
      15) fragment ion appears above 13 eV photon energy. This species can be produced
      directly from the parent ion or via two sequential dissociation channels: by
      acetyl radical loss from the acetone cation or CO-loss from the acetyl cation.

PMID- 27711605
TI  - Accurate nonadiabatic dynamics.
AB  - This Perspective addresses the use of coupled diabatic potential energy surfaces
      (PESs) together with rigorous quantum dynamics in full or reduced dimensional
      coordinate spaces to obtain accurate solutions to problems in nonadiabatic
      dynamics. A recently developed technique for obtaining the requisite diabatic
      PESs is reviewed. Three examples are considered in detail, two, H2O and NH3
      photodissociation, are treated in the full dimensionality while for the third,
      phenol photodissociation, a reduced dimensionality treatment is used. In all
      three examples, nonadiabatic dynamics is dominated by conical intersections, near
      which the Born-Oppenheimer approximation fails. The role of the conical
      intersection induced geometric phase in the adiabatic representation, as evinced
      by the molecular Aharonov-Bohm effect, is discussed.

PMID- 27711606
TI  - A unified description of the double perovskite family Sr2MWO6 within a rigid ion
      model.
AB  - The sequence of phase transitions and structural instabilities of the Sr2MWO6
      double perovskites are investigated using a rigid ion model. The parametrization
      of the short range empirical potential allows the control of the cation sizes by
      means of independent parameters, and in particular, the effective size of the M
      cation can be tuned to reproduce the behaviour of the whole family. The coupling
      of symmetry modes and its role in the stability of the phases are discussed, and
      molecular dynamics simulations are carried out to determine structural phase
      transitions as a function of temperature. A satisfactory agreement between
      experiments and ab initio calculations is obtained for the relevant range of
      ionic radii and temperatures, indicating that the range of stability of the
      structures is mainly governed by steric effects.

PMID- 27711607
TI  - Assessing Hubbard-corrected AM05+U and PBEsol+U density functionals for strongly
      correlated oxides CeO2 and Ce2O3.
AB  - The structure-property relationships of bulk CeO2 and Ce2O3 have been
      investigated using AM05 and PBEsol exchange-correlation functionals within the
      frameworks of Hubbard-corrected density functional theory (DFT+U) and density
      functional perturbation theory (DFPT+U). Compared with conventional PBE+U,
      RPBE+U, PW91+U and LDA+U functionals, AM05+U and PBEsol+U describe experimental
      crystalline parameters and properties of CeO2 and Ce2O3 with superior accuracy,
      especially when +U is chosen close to its value derived by the linear-response
      approach. The present findings call for a reexamination of some of the
      problematic oxide materials featuring strong f- and d-electron correlation using
      AM05+U and PBEsol+U.

PMID- 27711608
TI  - Half-metallic YN2 monolayer: dual spin filtering, dual spin diode and spin
      Seebeck effects.
AB  - Most of the pristine graphene-like two-dimensional materials have been found to
      be non-magnetic, and the emergence of magnetism usually needs an external
      electric field, substrate, strain, vacancy, or doping, which is not easily
      controlled in an experiment, limiting the potential applications in spintronics.
      Very recently, layered transition-metal dinitrides were explored experimentally
      and theoretically, and a pristine YN2 monolayer was predicted to be a half
      metallic ferromagnet with a graphene-like structure. To demonstrate the possible
      spintronic applications, herein, we designed spintronic devices based on the half
      metallic YN2 monolayer, and found perfect dual spin filtering and dual spin diode
      effects when a bias voltage was applied. Moreover, the devices also exhibited
      excellent spin Seebeck effects under a temperature gradient, which make the YN2
      monolayer a promising candidate for both spintronic and spin caloritronic
      applications. These peculiar spin transport properties were analyzed and
      explained from the calculated spin-resolved band structure and transmission
      spectrum based on first-principles combined with the non-equilibrium Green's
      function method.

PMID- 27711609
TI  - A new insight into pi-pi stacking involving remarkable orbital interactions.
AB  - For more than half a century, the phenomenon of pi-pi stacking has attracted much
      attention in several research fronts including materials science, chemical
      synthesis, and even drug design. Despite intense theoretical and experimental
      exploration, no unified description of the factors contributing to pi-pi stacking
      interactions and their weak bonding process has been proposed. In this work,
      based on calculations of the simplest prototype of pi-pi stacking, namely the
      benzene sandwich dimer (together with benzene-phenol, toluene and benzonitrile)
      using the density functional theory with dispersion correction, previously rarely
      studied intermolecular orbital interaction is discussed in detail and shown to
      involve considerable hybridizations of some of the orbitals which make a large
      contribution to the total interaction energy. We now propose a unified model for
      the often nebulous pi-pi stacking process and its analogs: firstly when the two
      monomers are too far apart, the dispersion effect will play a dominant role in
      bringing them together, but when they are too close, Pauli repulsion will force
      them apart. Secondly, at the equilibrium distance, electrostatic interaction,
      Pauli repulsion, dispersion and intermolecular orbital interaction are all
      pronounced, with part of the molecular orbitals of the two monomers interacting
      with each other to form a weak intermolecular bond.

PMID- 27711610
TI  - Modelling the structure of Zr-rich Pb(Zr1-xTix)O3, x = 0.4 by a multiphase
      approach.
AB  - Solid solution perovskite Pb(Zr1-xTix)O3 (PZT) is an industrially important
      material. Despite the long history of experimental and theoretical studies, the
      structure of this material is still under intensive discussion. In this work, we
      have applied structure searching coupled with density functional theory methods
      to provide a multiphase description of this material at x = 0.4. We demonstrate
      that the permutational freedom of B-site cations leads to the stabilisation of a
      variety of local phases reflecting a relatively flat energy landscape of PZT.
      Using a set of predicted local phases we reproduce the experimental pair
      distribution function (PDF) profile with high accuracy. We introduce a complex
      multiphase picture of the structure of PZT and show that additional monoclinic
      and rhombohedral phases account for a better description of the experimental PDF
      profile. We propose that such a multiphase picture reflects the entropy reached
      in the sample during the preparation process.

PMID- 27711611
TI  - Do group 1 metal salts form deep eutectic solvents?
AB  - Mixtures of metal salts such as ZnCl2, AlCl3 and CrCl3.6H2O form eutectic
      mixtures with complexing agents, such as urea. The aim of this research was to
      see if alkali metal salts also formed eutectics in the same way. It is shown that
      only a limited number of sodium salts form homogeneous liquids at ambient
      temperatures and then only with glycerol. None of these mixtures showed eutectic
      behaviour but the liquids showed the physical properties similar to the group of
      mixtures classified as deep eutectic solvents. This study focussed on four sodium
      salts: NaBr, NaOAc, NaOAc.3H2O and Na2B4O7.10H2O. The ionic conductivity and
      viscosity of these salts with glycerol were studied, and it was found that unlike
      previous studies of quaternary ammonium salts with glycerol, where the salt
      decreased the viscosity, most of the sodium salts increased the viscosity. This
      suggests that sodium salts have a structure making effect on glycerol. This
      phenomenon is probably due to the high charge density of Na+, which coordinates
      to the glycerol. 1H and 23Na NMR diffusion and relaxation methods have been used
      to understand the molecular dynamics in the glycerol-salt mixtures, and probe the
      effect of water on some of these systems. The results reveal a complex dynamic
      behaviour of the different species within these liquids. Generally, the
      translational dynamics of the 1H species, probed by means of PFG NMR diffusion
      coefficients, is in line with the viscosity of these liquids. However, 1H and
      23Na T1 relaxation measurements suggest that the Na-containing species also play
      a crucial role in the structure of the liquids.

PMID- 27711612
TI  - Bilayered graphene as a platform of nanostructures with folded edge holes.
AB  - The stability and the electronic properties of new AB-stacking and moire bilayer
      graphene superlattices with closed edge nanoholes are studied using DFT
      calculations. The closing of the edges is made of C-C bonds that form after
      folding the borders of the holes. Superlattices with periodic hexagonal symmetry
      are considered in more detail. The electronic band structure of the nanomeshes
      has metallic to semiconductor characteristics, depending not only on the size of
      the holes and the distance between them, but also on the hole shape. Bilayered
      graphene is considered as a platform for the engineering of nanostructures with
      folded edge holes.

PMID- 27711613
TI  - Improvement in surface-enhanced Raman spectroscopy from cubic SiC semiconductor
      nanowhiskers by adjustment of energy levels.
AB  - Enhanced reproducible Raman signals of the 4-MBA molecule were observed on the
      surface of semiconducting SiC nanowhiskers (SiCNWs) by surface-enhanced Raman
      spectroscopy (SERS). The SERS enhancement was further tuned and boosted by doping
      with B. Theoretical calculations were performed to unravel the mechanism of the
      SERS enhancement and it was found that the SERS effect was strongly associated
      with the energy level structure between the substrate and analyte. Appropriate
      energy level matching facilitated the charge transfer process during laser
      illumination, enhancing the SERS signal. This proposed mechanism was verified
      through multiple control experiments.

PMID- 27711614
TI  - Temperature- and pressure-dependent studies of niccolite-type formate frameworks
      of [NH3(CH2)4NH3][M2(HCOO)6] (M = Zn, Co, Fe).
AB  - We report temperature-dependent electric, IR and Raman studies of niccolite-type
      formate frameworks templated by protonated 1,4-diaminobutane. Our results show
      that the zinc-analogue exhibits a first-order phase transition close to 240 K.
      Single-crystal dielectric data show a much stronger anomaly at the phase
      transition for epsilon' along the a-direction compared to the c-direction. They
      also reveal that dipole relaxation exists in bnZn. Pronounced temperature
      dependence observed for bending and torsion modes of the NH3+ groups proves that
      ordering of protonated amine plays a major role in the phase transition
      mechanism. The ordering is associated with distortion of the zinc formate
      framework but the number of observed vibrational modes is much smaller than
      expected assuming 36-fold multiplication of the unit cell below TC. It is also
      much smaller than reported for the Mn-analogue, which exhibits only a two-fold
      increase of the unit cell below TC. We discuss the origin of this behavior. Our
      results also show that the Co-analogue exhibits a similar phase transition to its
      Zn-counterpart. However, the observed narrowing and splitting of the
      corresponding bands is significantly smaller, suggesting weaker distortion of the
      framework and the presence of some disorder for this compound even at 5 K. The
      Raman and IR spectra of the Fe-analogue show weak narrowing of bands upon
      cooling, indicative of statistical freezing of the protonated amine at low
      temperatures. We also report high-pressure Raman scattering studies of the zinc
      analogue. This study revealed a pressure-induced reversible phase transition
      between 3.4 and 4.1 GPa. Large shifts and splitting of modes corresponding to the
      vibrations of HCOO- ions associated with weak changes of the protonated amine
      prove that the major contribution to the phase transition mechanism comes from
      distortion of the zinc formate framework.

PMID- 27711615
TI  - Multiple-decker and ring sandwich formation of manganese-benzene organometallic
      cluster anions: MnnBzn- (n = 1-5 and 18).
AB  - Organometallic multiple-decker sandwich clusters are topics of great interest due
      to their unique electronic and magnetic properties originating from anisotropic
      structures. We report a joint anion photoelectron spectroscopic and computational
      study on a new family of manganese (Mn)-benzene (Bz) anionic clusters MnnBzn-. In
      stark contrast to the most widely studied vanadium-Bz sandwich clusters, it is
      found that MnnBzn- (n = 1-5) clusters exhibit unprecedented multiple-decker
      structures with a tilted Mn-Bz stacking and a monotonically increasing behavior
      of their high spin multiplicities. Furthermore, a couple of closed ring forms of
      Mn18Bz18- and its neutral state are computationally anticipated as an intriguing
      "cluster of Mn1Bz1 clusters" in which the neutral Mn18Bz18 has extremely high
      C18h symmetry with an uncommon spin state of 2S + 1 = 55. The extensively
      delocalized electron environment of Mn18Bz18 allows the simple Huckel model to
      reveal the strong intra-atomic exchange interactions within the Mn 3d electrons.

PMID- 27711616
TI  - Nanoparticle electrochemistry.
AB  - This perspective article provides a survey of recent advances in nanoscale
      electrochemistry, with a brief theoretical background and a detailed discussion
      of experimental results of nanoparticle based electrodes, including the rapidly
      expanding field of "impact electrochemistry". Following this, recent advances in
      experimental study of exotic nanoparticle electrodes are reviewed.

PMID- 27711617
TI  - Investigation on the conversion of ethylene to ethylidyne on Pt(100) and Pd(100)
      using density functional theory.
AB  - The comprehensive formation network of ethylidyne (CH3C) from ethylene (CH2CH2)
      is investigated on Pt(100) and Pd(100) using the density functional theory
      method. The structural and energetic features of all intermediate products were
      considered. We found that the trend of the activation barriers in each pathway on
      Pt(100) and Pd(100) are the same, whereas the barriers on Pt(100) are higher than
      that on Pd(100). The activation barriers of 1,2-H shift reactions are relatively
      high compared with the other reactions. We screened three possible pathways and
      selected the optimal route as CH2CH2(ethylene) -> CH2CH(vinyl) ->
      CH2C(vinylidene) -> CH3C(ethylidyne).

PMID- 27711618
TI  - Structure-dependent vibrational dynamics of Mg(BH4)2 polymorphs probed with
      neutron vibrational spectroscopy and first-principles calculations.
AB  - The structure-dependent vibrational properties of different Mg(BH4)2 polymorphs
      (alpha, beta, gamma, and delta phases) were investigated with a combination of
      neutron vibrational spectroscopy (NVS) measurements and density functional theory
      (DFT) calculations, with emphasis placed on the effects of the local structure
      and orientation of the BH4- anions. DFT simulations closely match the neutron
      vibrational spectra. The main bands in the low-energy region (20-80 meV) are
      associated with the BH4- librational modes. The features in the intermediate
      energy region (80-120 meV) are attributed to overtones and combination bands
      arising from the lower-energy modes. The features in the high-energy region (120
      200 meV) correspond to the BH4- symmetric and asymmetric bending vibrations, of
      which four peaks located at 140, 142, 160, and 172 meV are especially intense.
      There are noticeable intensity distribution variations in the vibrational bands
      for different polymorphs. This is explained by the differences in the spatial
      distribution of BH4- anions within various structures. An example of the possible
      identification of products after the hydrogenation of MgB2, using NVS
      measurements, is presented. These results provide fundamental insights of benefit
      to researchers currently studying these promising hydrogen-storage materials.

PMID- 27711619
TI  - Ligand effects on the optical and chiroptical properties of the thiolated Au18
      cluster.
AB  - The effect of chiral and achiral ligands protecting the inner Au9 core of the
      Au18(SR)14 cluster is studied based on density functional theory (DFT) and its
      corrected long-range interaction (DFT-D) approach. It was found that the
      electronic properties (energy levels) depend on the specific ligands, which
      induce distinct distortions on the Au-S framework. However, the substitution of S
      c-C6H11 as SCH3 ligands may be considered to be correct given the obtained
      resemblance to the displayed bonding, optical and chiroptical properties. A
      further comparison of the CD and UV spectra displayed by the Au18 cluster
      protected by chiral and achiral ligands attests that more intense profiles are
      featured by ligands including phenyl rings and/or oxygen atoms such that the Au18
      cluster protected by either achiral meta-mercaptobenzoic acid (m-MBA) or achiral
      SPh ligands displays more intense UV and CD signals. These results provide new
      insight into the effect of ligands on thiolated gold clusters.

PMID- 27711620
TI  - In situ S-K XANES study of polymer electrolyte fuel cells: changes in the
      chemical states of sulfonic groups depending on humidity.
AB  - Changes in the chemical states of sulfonic groups of Nafion in polymer
      electrolyte fuel cells (PEFCs) under gas-flowing conditions were studied using in
      situ S-K XANES spectroscopy. The applied potential to the electrodes and the
      humidity of the cell were changed under flowing H2 gas in the anode and He gas in
      the cathode. While the potential shows no significant effect on the S-K XANES
      spectra, the humidity is found to induce reversible changes in the spectra.
      Comparison of the spectral changes with simulations based on the density
      functional theory calculations indicates that the humidity influences the
      chemical state of the sulfonic group; under wet conditions the sulfonic group is
      in the form of a sulfonate ion. By drying treatment the sulfonate ion binds to
      hydrogen and becomes sulfonic acid. Furthermore, a small fraction of the sulfonic
      acid irreversibly decomposes to atomic sulfur. The peak energy of the atomic
      sulfur suggests that the generated atomic sulfur is adsorbed on the Pt catalyst
      surfaces.

PMID- 27711621
TI  - Tuning the thermoelectric properties of A-site deficient SrTiO3 ceramics by
      vacancies and carrier concentration.
AB  - Ceramics based on Sr0.8La0.067Ti0.8Nb0.2O3-delta have been prepared by the mixed
      oxide route. The La1/3NbO3 component generates ~13.4% A-site vacancies; this was
      fixed for all samples. Powders were sintered under air and reducing conditions at
      1450 to 1700 K; products were of high density (>90% theoretical). Processing
      under reducing conditions led to the formation of a Ti1-xNbxO2-y second phase,
      core-shell structures and oxygen deficiency. X-ray diffraction (XRD) confirmed a
      simple cubic structure with space group Pm3[combining macron]m. Transmission
      electron microscopy revealed a high density of dislocations while analytical
      scanning transmission electron microscopy at atomic resolution demonstrated a
      uniform distribution of La, Nb and vacancies in the lattice. X-ray photoemission
      spectroscopy and thermogravimetry showed the oxygen deficiency (delta value) to
      be ~0.08 in reduced samples with enhanced carrier concentrations ~2 * 1021 cm-3.
      Both carrier concentration and carrier mobility increased with sintering time,
      giving a maximum figure of merit (ZT) of 0.25. Selective additional doping by La
      or Nb, with no additional A site vacancies, led to the creation of additional
      carriers and reduced electrical resistivity. Together these led to enhanced ZT
      values of 0.345 at 1000 K. The contributions from oxygen vacancies and charge
      carriers have been investigated independently.

PMID- 27711622
TI  - Elucidation of the local dynamics of domain-III of human serum albumin over the
      ps-MUs time regime using a new fluorescent label.
AB  - The ps-MUs dynamics of domain-III of human serum albumin (HSA) has been
      investigated using a new fluorescent marker selectively labeled to the Tyr-411
      residue. The location of the marker has been confirmed using Forster resonance
      energy transfer (FRET) study. Steady state, time-resolved and single molecular
      level fluorescence techniques have been employed to understand the dynamics
      within the domain-III of HSA. It is found that solvent reorganization dynamics in
      domain-III is 1.7 times faster than that in domain-I. The timescale of the local
      rotational dynamics of domain-III is found to be 2.3 times faster than that of
      domain-I. Fluorescence correlation spectroscopic experiments reveal that domain
      III of HSA has more conformational flexibility than domain-I. Together, the
      results deliver useful details of the local environment around the domain-III of
      HSA, which have not been explored earlier, mainly because of a lack of a suitable
      fluorescent marker for domain-III. The newly synthesized probe serves well as a
      site specific fluorescent marker for HSA, and can be used for further
      investigation of the ligand binding properties and enzymatic activity of domain
      III of HSA.

PMID- 27711623
TI  - The computational prediction of Raman and ROA spectra of charged histidine
      tautomers in aqueous solution.
AB  - Histidine is a key component of a number of enzymatic mechanisms, and undertakes
      a myriad of functionalities in biochemical systems. Its computational modelling
      can be problematic, as its capacity to take on a number of distinct formal charge
      states, and tautomers thereof, is difficult to capture by conventional
      techniques. We demonstrate a means for recovering the experimental Raman optical
      activity (ROA) spectra of histidine to a high degree of accuracy. The resultant
      concordance between experiment and theory is of particular importance in
      characterising physically insightful quantities, such as band assignments. We
      introduce a novel conformer selection scheme that unambiguously parses snapshots
      from a molecular dynamics trajectory into a smaller conformational ensemble,
      suitable for reproducing experimental spectra. We show that the "dissimilarity"
      of the conformers within the resultant ensemble is maximised and representative
      of the physically relevant regions of molecular conformational space. In
      addition, we present a conformer optimisation strategy that significantly reduces
      the computational costs associated with alternative optimisation strategies. This
      conformer optimisation strategy yields spectra of equivalent quality to those of
      the aforementioned alternative optimisation strategies. Finally, we demonstrate
      that microsolvated models of small molecules yield spectra that are comparable in
      quality to those obtained from ab initio calculations involving a large number of
      solvent molecules.

PMID- 27711624
TI  - The photophysics of photoredox catalysis: a roadmap for catalyst design.
AB  - Recently, the use of transition metal based chromophores as photo-induced single
      electron transfer reagents in synthetic organic chemistry has opened up a wealth
      of possibilities for reinventing known reactions as well as creating new pathways
      to previously unattainable products. The workhorses for these efforts have been
      polypyridyl complexes of Ru(ii) and Ir(iii), compounds whose photophysics have
      been studied for decades within the inorganic community but never extensively
      applied to problems of interest to organic chemists. While the nexus of synthetic
      organic and physical-inorganic chemistries holds promise for tremendous new
      opportunities in both areas, a deeper appreciation of the underlying principles
      governing the excited-state reactivity of these charge-transfer chromophores is
      needed. In this Tutorial Review, we present a basic overview of the photophysics
      of this class of compounds with the goal of explaining the concepts, ground- and
      excited-state properties, as well as experimental protocols necessary to probe
      the kinetics and mechanisms of photo-induced electron and/or energy transfer
      processes.

PMID- 27711625
TI  - The rectifying and negative differential resistance effects in graphene/h-BN
      nanoribbon heterojunctions.
AB  - We investigate the electronic transport properties of four types of lateral
      graphene/h-BN nanoribbon heterojunctions using the non-equilibrium Green's
      function method in combination with the density functional theory. The results
      show that the heterojunction displays an interesting rectifying effect when the
      interface has a left-right type structure, while a pronounced negative
      differential resistance (NDR) effect when the interface has an up-down type
      structure. Moreover, when the interface of the heterojunction has a left-bank or
      right-bank type structure, it presents the rectifying (with a larger
      rectification ratio) and NDR effects. This work is helpful to further construct
      and prepare a nanodevice based on the graphene/h-BN heterojunction materials
      according to the proposed structures.

PMID- 27711626
TI  - Band-structure engineering in conjugated 2D polymers.
AB  - Conjugated polymers find widespread application in (opto)electronic devices,
      sensing, and as catalysts. Their common one-dimensional structure can be extended
      into the second dimension to create conjugated planar sheets of covalently linked
      molecules. Extending pi-conjugation into the second dimension unlocks a new class
      of semiconductive polymers which as a consequence of their unique electronic
      properties can find usability in numerous applications. In this article the
      theoretical band structures of a set of conjugated 2D polymers are compared and
      information on the important characteristics band gap and valence/conduction band
      dispersion is extracted. The great variance in these characteristics within the
      investigated set suggests 2D polymers as exciting materials in which band
      structure engineering can be used to tailor sheet-like organic materials with
      desired electronic properties.

PMID- 27711627
TI  - Electrochemical oxidation of dihydronicotinamide adenine dinucleotide (NADH):
      comparison of highly oriented pyrolytic graphite (HOPG) and polycrystalline boron
      doped diamond (pBDD) electrodes.
AB  - The electro-oxidation of nicotinamide adenine dinucleotide (NADH) is studied at
      bare surfaces of highly oriented pyrolytic graphite (HOPG) and semi-metallic
      polycrystalline boron-doped diamond (pBDD). A comparison of these two carbon
      electrode materials is interesting because they possess broadly similar densities
      of electronic states that are much lower than most metal electrodes, but graphite
      has carbon sp2-hybridization, while in diamond the carbon is sp3-hybridised, with
      resulting major differences in bulk structure and surface termination. Using
      cyclic voltammetry (CV), it is shown that NADH oxidation is facile at HOPG
      surfaces but the reaction products tend to strongly adsorb, which causes rapid
      deactivation of the electrode activity. This is an important factor that needs to
      be taken into account when assessing HOPG and its intrinsic activity. It is also
      shown that NADH itself adsorbs at HOPG, a fact that has not been recognized
      previously, but has implications for understanding the mechanism of the electro
      oxidation process. Although pBDD was found to be less susceptible to surface
      fouling, pBDD is not immune to deterioration of the electrode response, and the
      reaction showed more sluggish kinetics on this electrode. Scanning
      electrochemical cell microscopy (SECCM) highlights a significant voltammetric
      variation in electroactivity between different crystal surface facets that are
      presented to solution with a pBDD electrode. The electroactivity of different
      grains correlates with the local dopant level, as visualized by field emission
      scanning electron microscopy. SECCM measurements further prove that the basal
      plane of HOPG has high activity towards NADH electro-oxidation. These new
      insights on NADH voltammetry are useful for the design of optimal carbon-based
      electrodes for NADH electroanalysis.

PMID- 27711628
TI  - Hydrogen bonding and delocalization in the ELF analysis approach.
AB  - Delocalization of the electron density in the proton donor fragment has been
      studied for 21 complexes, A-HB (A = F, Cl; B = Ne, Ar, CO2, N2, FH, ClH, H2O,
      PH3, NH3, Cl-, F-, covering the whole range of hydrogen bond strength. The proton
      donor and proton acceptor fragments are defined by a minimum variance principle
      achieved by the ELF partition. It is shown that the variance of the proton donor
      population as well as the charge transfer between the fragments calculated from
      the ELF partition is always smaller than that evaluated within the QTAIM
      framework. For both partition schemes, the variance and the charge transfer are
      correlated with the hydrogen bond strength. It is shown that the variance varies
      as the square root of the value of the ELF at the hydrogen bond interaction point
      (i.e. the saddle point at the boundary of the proton donor and proton acceptor
      moieties)etavv' providing a numerical proof of the conjecture that the ELF
      partition satisfies a minimum variance condition and an explanation of the
      success of the core valence bifurcation index as an indicator of the hydrogen
      bond strength. The ELF technique has been then applied to the study of hydrogen
      bonded crystals for which the variance of the fragment population has been
      estimated from etavv'. The systems investigated are KHF2, KDP and ice VIII. The
      results are consistent with very strong hydrogen bonds in the two former crystals
      and medium-weak bonding in ice. In ice VIII the variance, and therefore the
      hydrogen bond strength, increases with pressure yielding a phase transition
      toward ice X in which the hydrogen bond is characterized as very strong. Our
      study emphasizes the importance of the partition scheme which defines the proton
      donor fragment and the role of electron density delocalization between the
      fragments which is, according to us, often improperly termed as covalence.

PMID- 27711629
TI  - Prediction of flatness-driven quantum spin Hall effect in functionalized
      germanene and stanene.
AB  - Searching for realistic materials able to realize room-temperature quantum spin
      Hall (QSH) effects is currently a growing field, especially when compatibility
      with the current group-IV electronics industry is required. Here we predict,
      through first-principles calculations, a new class of QSH phases in flattened
      germanene and stanene functionalized with X atoms (f-GeX2 and f-SnX2; X = H, F,
      Cl, Br, I) with a bulk gap as large as 0.56 eV, that can be tuned efficiently
      under mechanical strain. More interestingly, different from the normal band order
      in buckled germanane and stanane, the structural flatness leads to an inverted
      band order without spin-orbit coupling (SOC), whereas the SOC only opens the band
      gap. We also find that the characteristics of edge states, such as the Fermi
      velocity, are enhanced greatly by edge modification. When these films are
      deposited on a BN substrate, a nontrivial QSH state is preserved with a Dirac
      cone lying within the nontrivial band gap. These findings provide a promising
      platform for future realistic applications of the QSH effect at room temperature
      in two-dimensional group-IV films.

PMID- 27711630
TI  - Crystal structure, luminescence properties, energy transfer and thermal
      properties of a novel color-tunable, white light-emitting phosphor Ca9-x
      yCe(PO4)7:xEu2+,yMn2.
AB  - A series of Ca9-x-yCe(PO4)7:xEu2+,yMn2+ phosphors were synthesized by a high
      temperature solid-state reaction method. The as-prepared samples were
      characterized by XRD and EDX measurements, which showed that Eu2+ and Mn2+ could
      be efficiently doped into the host. Ce3+ acts concurrently as activator and
      sensitizer in Ca9Ce(PO4)7, and the energy transfer mechanisms between Ce3+/Eu2+
      and Ce3+/Mn2+ in Ca9Ce(PO4)7 were validated and proven to be a resonant type via
      dipole-quadrupole and dipole-dipole interactions, respectively. Besides, there is
      also energy transfer from Eu2+ to Mn2+ ions. The host, Ca9Ce(PO4)7, emits blue
      white light and Ca9Ce(PO4)7:xEu2+,yMn2+ phosphors emit blue-green through white
      to orange-red light under near-ultraviolet radiation as a result of tuning the
      ratio of Eu2+/Mn2+. Ca9Ce(PO4)7:0.04Eu2+,0.08Mn2+ emits white light with CIE
      coordinates (0.333, 0.310), a CCT of 5446 K, and a high CRI of 81. The energy
      transfer efficiency between Ce3+ and Mn2+ increases significantly with
      temperature. These results reveal that Ca9Ce(PO4)7:Eu2+,Mn2+ may be a potential
      candidate for white light-emitting phosphors.

PMID- 27711631
TI  - Characterization of step-edge barrier crossing of para-sexiphenyl on the ZnO
      (101[combining macron]0) surface.
AB  - Mass transport processes of conjugated organic molecules (COMs) on inorganic
      surfaces are essential elements in thin film deposition for hybrid optoelectronic
      devices. Defects and in particular surface step-edges dictate the molecular
      nucleation and growth morphology, which itself determine many physical properties
      of the resulting hybrid interface. Here, we explore the detailed molecular
      kinetics and transport rates of a single physisorbed para-sexiphenyl (p-6P)
      molecule crossing a step-edge (a "hetero-Ehrlich-Schwoebel barrier") on the
      inorganic ZnO (101[combining macron]0) surface by a combination of all-atom
      molecular dynamics simulations and passage time theory. We determine temperature-
      and charge-dependent (free) energy landscapes, position-dependent diffusion
      coefficients, and ultimately the mean first passage time over the step-edges. We
      find two completely different step-edge crossing mechanisms, the occurrence and
      rates of which simultaneously depend on both electrostatic and thermal molecule
      surface coupling. In weakly coupled systems, the molecule crosses the step
      relatively quickly (in nanoseconds) by log-roll mechanisms while for strongly
      coupled systems, it crosses relatively slowly (in microseconds) in a strictly
      perpendicular fashion. In the latter process, "internal friction" from
      intramolecular bending and torsional degrees of freedom contribute a significant
      corrugation to the overall crossing barrier. Furthermore, we show that crossing
      pathways can also change qualitatively with step-edge height. The great
      complexity in hetero-barrier crossing of COMs (in contrast to simple atoms)
      revealed in this study has implications on the interpretation and possible
      control of nucleation and growth mechanisms at surface defects in hybrid systems.

PMID- 27711632
TI  - A search map for organic additives and solvents applicable in high-voltage
      rechargeable batteries.
AB  - Chemical databases store information such as molecular formulas, chemical
      structures, and the physical and chemical properties of compounds. Although the
      massive databases of organic compounds exist, the search of target materials is
      constrained by a lack of physical and chemical properties necessary for specific
      applications. With increasing interest in the development of energy storage
      systems such as high-voltage rechargeable batteries, it is critical to find new
      electrolytes efficiently. Here we build a search map to screen organic additives
      and solvents with novel core and functional groups, and thus establish a database
      of electrolytes to identify the most promising electrolyte for high-voltage
      rechargeable batteries. This search map is generated from MAssive Molecular Map
      BUilder (MAMMBU) by combining a high-throughput quantum chemical simulation with
      an artificial neural network algorithm. MAMMBU is designed for predicting the
      oxidation and reduction potentials of organic compounds existing in the massive
      organic compound database, PubChem. We develop a search map composed of ~1 000
      000 redox potentials and elucidate the quantitative relationship between the
      redox potentials and functional groups. Finally, we screen a quinoxaline compound
      for an anode additive and apply it to electrolytes and improve the capacity
      retention from 64.3% to 80.8% near 200 cycles for a lithium ion battery in
      experiments.

PMID- 27711633
TI  - Anomalous pressure effects on the photoreaction of a light-sensor protein from
      Synechocystis, PixD (Slr1694), and the compressibility change of its
      intermediates.
AB  - SyPixD (Slr1694) is a blue-light receptor that contains a BLUF (blue-light sensor
      using a flavin chromophore) domain for the function of phototaxis. The key
      reaction of this protein is a light-induced conformational change and subsequent
      dissociation reaction from the decamer to the dimer. In this study, anomalous
      effects of pressure on this reaction were discovered, and changes in the
      compressibility of its short-lived intermediates were investigated. While the
      absorption spectra of the dark and light states are not sensitive to pressure,
      the formation yield of the first intermediate decreases with pressure to about
      40% at 150 MPa. Upon blue-light illumination with a sufficiently strong
      intensity, the transient grating signal, which represents the dissociation of the
      SyPixD decamer, was observed at 0.1 MPa, and the signal intensity significantly
      decreased with increasing pressure. This behavior shows that the dissociation of
      the decamer from the second intermediate state is suppressed by pressure.
      However, while the decamer undergoes no dissociation upon excitation of one
      monomer unit at 0.1 MPa, dissociation is gradually induced with increasing
      pressure. For solving this strange behavior, the compressibility changes of the
      intermediates were measured as a function of pressure at weak light intensity.
      Interestingly, the compressibility change was negative at low pressure, but
      became positive with increasing pressure. Because the compressibility is related
      to the volume fluctuation, this observation suggests that the driving force for
      this reaction is fluctuation of the protein. The relationship between the
      cavities at the interfaces of the monomer units and the reactivity was also
      discussed.

PMID- 27711634
TI  - New solvatochromic probes: performance enhancement via regulation of excited
      state structures.
AB  - A new fluorescent conjugate (PNBD) with a structure of D-pi-A was designed and
      synthesized, where the donor (D), the acceptor (A) and the bridge (pi) are
      naphthalyl, dicyanovinyl and phenylethynyl-phenylethynyl, respectively. To
      improve the solubility of the conjugate, two long alkyl chains were introduced as
      substituents of the central aromatic ring. Spectroscopic studies demonstrated
      that PNBD is a strongly solvatochromic probe which is characterized by a large
      molar absorption coefficient (>32 000 cm-1 M-1), long wavelength absorption (>410
      nm), large solvatochromic emission range (470-650 nm), high photochemical
      stability, and good solubility in common organic solvents. The fluorescent
      quantum yield of PNBD is limited in some polar solvents due to dual emission, a
      phenomenon ascribed to radiative decay from a higher excited singlet state. To
      eliminate dual emission, a covalently bound dimer (BPNBD) of PNBD characterized
      by weak vibronic coupling, was designed and synthesized. The dimer constituents
      are linked by a single bond between the naphthalyl moieties of the two PNBD
      monomers. As expected, BPNBD maintains almost all the strong points of the
      monomer, exhibits a substantial increase in fluorescence quantum yield, and
      eliminates dual emission by facilitating efficient internal conversion.
      Importantly, the use of PNBD and BPNBD in concert provides unprecedented
      discrimination among solvents of similar structures, such as (CH2Cl2, CHCl3,
      CCl4), (ethyl ether, THF, dioxane), or (methanol, ethanol, n-propanol, n-butanol,
      n-pentanol, n-hexanol, n-heptanol, n-octanol, n-decanol), allowing rapid and
      selective visual identification.

PMID- 27711635
TI  - Mass effects in the photodissociation of homonuclear diatomic molecules in helium
      nanodroplets: inelastic collision and viscous flow energy exchange regimes.
AB  - The influence of the mass in the photodissociation dynamics of a homonuclear
      diatomic molecule (X2), embedded in a superfluid helium nanodroplet (T = 0.37 K)
      of 300 atoms, has been investigated using a hybrid quantum dynamics method
      recently proposed by us. Several hypothetical isotopic variants of Cl2 have been
      examined in order to make possible the analysis of a wide diversity of masses
      (mX: 0.25mCl-1.50mCl). This is probably the first time that this problem has been
      considered theoretically. The photodissociation mechanism of X2(B) is very
      similar to that of Cl2(B) and the efficiency of the X2-helium energy exchange
      mechanism can be so great that it leads to the full and partial (~86%) geminate
      recombination for the lower masses explored (mX = 0.25mCl and 0.50mCl,
      respectively). From the energy exchange perspective two dynamic regimes have been
      identified. The first regime occurs at the initial times of the photodissociation
      and corresponds to a perfectly inelastic collision (IC) between the atomic
      fragments (X) and some helium atoms of the solvation shell. The second regime
      occurs when the atomic fragments are moving through the nanodroplet, which
      behaves as a viscous fluid (VF). The ICVF mechanism has probably general
      character in the photodissociation of molecules embedded in superfluid helium
      nanodroplets.

PMID- 27711636
TI  - Transition metal-catalysed couplings between arenes and strained or reactive
      rings: combination of C-H activation and ring scission.
AB  - Organic transformations that involve direct functionalization of C-H bonds
      represent an attractive synthetic strategy that maximizes atom- and step-economy.
      With the generally high stability of C-H bonds, these processes have mostly
      required harsh reaction conditions, in combination with the necessity of
      activation of the C-H substrates and/or the coupling partners. As a class of
      activated coupling partners, strained or reactive rings exhibited high activity
      in the coupling with aryl and alkyl C-H bonds. Such a high reactivity of the
      rings allowed the facile construction of various new structural platforms via
      coupling with scission of the ring structures. The combination of C-H activation
      and scission of the rings allowed for applications of a broader scope of C-H
      bonds, including those less reactive alkyl ones. This synthetic diversity of
      these rings has been realized owing to the intrinsically different mechanisms of
      the interactions of transition metal catalysts and the strained/reactive rings.

PMID- 27711637
TI  - Metallic cyanoacetylides of copper, silver and gold: generation and structural
      characterization.
AB  - The metallic cyanoacetylides CuCCCN, AgCCCN, and AuCCCN have been synthesized in
      the throat of a pulsed supersonic expansion by reaction of metal vapors, produced
      by laser ablation, and BrCCCN. Their pure rotational spectra in the (X1Sigma+)
      electronic ground state were observed by Fourier transform microwave spectroscopy
      in the 2-10 GHz frequency region. Importantly, the rotational spectroscopy
      constants determined from the analysis of the rotational spectra clearly
      established the existence of metal-CCCN arrangements for all the mentioned
      cyanoacetylides. A study of the chemical bonding by means of a topological
      analysis of the electron density helps to understand the preference for metal-C
      bonding over metal-N bonding.

PMID- 27711638
TI  - Interfacial charge separation and photovoltaic efficiency in Fe(ii)-carbene
      sensitized solar cells.
AB  - The first combined theoretical and photovoltaic characterization of both
      homoleptic and heteroleptic Fe(ii)-carbene sensitized photoanodes in working dye
      sensitized solar cells (DSSCs) has been performed. Three new heteroleptic Fe(ii)
      NHC dye sensitizers have been synthesized, characterized and tested. Despite an
      improved interfacial charge separation in comparison to the homoleptic compounds,
      the heteroleptic complexes did not show boosted photovoltaic performances. The ab
      initio quantitative analysis of the interfacial electron and hole transfers and
      the measured photovoltaic data clearly evidenced fast recombination reactions for
      heteroleptics, even associated with un unfavorable directional electron flow, and
      hence slower injection rates, in the case of homoleptics. Notably, quantum
      mechanics calculations revealed that deprotonation of the not anchored carboxylic
      function in the homoleptic complex can effectively accelerate the electron
      injection rate and completely suppress the electron recombination to the oxidized
      dye. This result suggests that introduction of strong electron-donating
      substituents on the not-anchored carbene ligand in heteroleptic complexes, in
      such a way of mimicking the electronic effects of the carboxylate functionality,
      should yield markedly improved interfacial charge generation properties. The
      present results, providing for the first time a detailed understanding of the
      interfacial electron transfers and photovoltaic characterization in Fe(ii)
      carbene sensitized solar cells, open the way to a rational molecular engineering
      of efficient iron-based dyes for photoelectrochemical applications.

PMID- 27711639
TI  - Calculations of the light absorption spectra of porphyrinoid chromophores for dye
      sensitized solar cells.
AB  - Solar power is a strong alternative to the currently used fossil fuels in order
      to satisfy the world's energy needs. Among them, dye-sensitized solar cells
      (DSSC) represent a low-cost option. Efficient and cheap dyes are currently needed
      to make DSSCs competitive. Computational chemistry can be used to guide the
      design of new light-absorbing chromophores. Here, we have computationally studied
      the lowest excited states of ZnPBAT, which is a recently synthesized porphyrinoid
      chromophore with high light-absorption efficiency. The calculations have been
      performed at ab initio correlated levels of theory employing second-order coupled
      clusters (CC2) and algebraic diagrammatic construction using second order
      (ADC(2)) methods and by performing density functional theory (DFT) calculations
      using the time-dependent DFT (TDDFT) approach for excitation energies. The
      ultraviolet-visible (UV-vis) spectrum calculated at the ADC(2) and CC2 levels
      agrees well with the experimental one. The calculations show that ZnPBAT has six
      electronic transitions in the visible range of the absorption spectrum. The ab
      initio correlated calculations and previously reported experimental data have
      been used to assess the performance of several well-known density functionals
      that have been employed in the present TDDFT study. Solvent effects have been
      estimated by using the conductor-like screening model (COSMO). The influence of
      the addition of a TiO2 cluster to the chromophore systems has also been
      investigated. The results indicate that both CAM-B3LYP and Becke's "half-and
      half" (BHLYP) density functionals are appropriate for the studies of excitation
      energies in the blue range of the visible spectrum for these kinds of
      porphyrinoid chromophores, whereas the excitation energies of the Q band
      calculated at the ab initio correlated level are more accurate than those
      obtained in the present TDDFT calculations. The inclusion of solvent effects has
      a modest influence on the spectrum of the protonated form of the studied
      chromophores, whereas solvent models are crucial when studying the absorption
      spectrum of the anionic chromophore. The calculated UV-vis spectrum for the
      chromophore anion is not significantly affected by attaching a TiO2 cluster to
      it.

PMID- 27711640
TI  - Correction: Effect of lipid head group interactions on membrane properties and
      membrane-induced cationic beta-hairpin folding.
AB  - Correction for 'Effect of lipid head group interactions on membrane properties
      and membrane-induced cationic beta-hairpin folding' by Sai J. Ganesan et al.,
      Phys. Chem. Chem. Phys., 2016, 18, 17836-17850.

PMID- 27711641
TI  - Establishing the pivotal role of local aromaticity in the electronic properties
      of boron-nitride graphene lateral hybrids.
AB  - Within an attempt to unravel the conundrum of irregular bandgap variations in
      hybrids of white-graphene (hBN) and graphene (G) observed in both experiment and
      theory, strong proofs about the decisive role of aromaticity in their electronic
      properties are brought to light. Sound numerical experiments conducted on zero-,
      one- and two-dimensional hBNG hybrids demonstrate that upon structural and/or
      electronic perturbation caused by foreign doping agents, the uniformity in local
      cyclic electron delocalization of ideal graphene restructures locally creating
      carbon hexagons of contrasting cyclic electron delocalization (c.c. local
      aromatic patterns) which may dominate the bandgap size of the resulting systems.
      In addition, relying on the quantum chemical aspect of aromaticity in terms of
      quantitative computations of cyclic electron delocalization together with
      pictorial intrinsic polarizability density representations, this work provides a
      solid and handy rule-of-thumb to be used in qualitative and intuitive
      predictions. According to this empirical rule, the origin of any nonmonotonic
      bandgap variation observed in stoichiometric 0D (BN)n/graphene hybrids with
      increasing hBN segment lies in instabilities caused by partially substituted
      benzenoid rings formed locally at the hBNG interfaces. This relationship,
      established in 0D graphene flakes and extended to 1D periodic ribbons, can be
      used to understand and qualitatively predict conflicting bandgap variations of
      vacancy-free 2D periodic lattices, pointing at the property of aromaticity as the
      missing link needed to solve the puzzle of conflicting bandgap variations in hBNG
      hybrids observed in experiment.

PMID- 27711642
TI  - Stress-strain behavior of block-copolymers and their nanocomposites filled with
      uniform or Janus nanoparticles under shear: a molecular dynamics simulation.
AB  - Although numerous research studies have been focused on studying the self
      assembled morphologies of block-copolymers (BCPs) and their nanocomposites,
      little attention has been directed to explore the relation between their ordered
      structures and the resulting mechanical properties. We adopt coarse-grained
      molecular dynamics simulation to study the influence of the morphologies on the
      stress-strain behavior of pure block copolymers and block copolymers filled with
      uniform or Janus nanoparticles (NPs). At first, we examine the effect of the
      arrangement (di-block, tri-block, alternating-block) and the components of the
      pure block copolymers, and by varying the component ratio between A and B blocks,
      spherical, cylindrical and lamellar phases are all formed, showing that spherical
      domains bring the largest reinforcing effect. Then by studying BCPs filled with
      NPs, the Janus NPs induce stronger bond orientation of polymer chains and greater
      mechanical properties than the uniform NPs, when these two kinds of NPs are both
      located in the interface region. Meanwhile, some other anisotropic Janus NPs,
      such as Janus rods and Janus sheets, are incorporated to examine the effect on
      the morphology and the stress-strain behavior. These findings deepen our
      understanding of the morphology-mechanics relation of BCPs and their
      nanocomposites, opening up a vast number of approaches such as designing the
      arrangement and components of BCPs, positioning uniform or Janus NPs with
      different shapes and shear flow to tailor their stress-strain performance.

PMID- 27711643
TI  - Two-dimensional exciton properties in monolayer semiconducting phosphorus
      allotropes.
AB  - Excitons play a key role in technological applications since they have a strong
      influence on determining the efficiency of photovoltaic devices. Recently, it has
      been shown that the allotropes of phosphorus possess an optical band gap that can
      be tuned over a wide range of values including the near-infrared and visible
      spectra, which would make them promising candidates for optoelectronic
      applications. In this work we carry out ab initio many-body perturbation theory
      calculations to study the excitonic effects on the optical properties of two
      dimensional phosphorus allotropes: the case of blue and black monolayers. We
      elucidate the most relevant optical transitions, exciton binding energy spectrum
      as well as real-space exciton distribution, particularly focusing on the
      absorption spectrum dependence on the incident light polarization. In addition,
      based on our results, we use a set of effective hydrogenic models, in which the
      electron-hole Coulomb interaction is included to estimate exciton binding
      energies and radii. Our results show an excellent agreement between the many-body
      methodology and the effective models.

PMID- 27711644
TI  - Probing the low-energy structures of aluminum-magnesium alloy clusters: a
      detailed study.
AB  - The effect of Mg doping on the growth behavior and the electronic properties of
      aluminum clusters has been investigated theoretically using the CALYPSO (Crystal
      structure AnaLYsis by Particle Swarm Optimization) method in combination with
      density functional theory calculations. Compared to pure aluminum clusters, the
      structure of Mg-doped clusters shows the charming transformation with increasing
      atomic number. The photoelectron spectra (PES) of the global minima of anionic
      Aln and AlnMg (n = 3-20) clusters have been calculated based on the time
      dependent density functional theory (TD-DFT) method. The reliability of our
      theoretical methodology is easily corroborated by the good agreement between the
      experimental PES and the simulated spectra. Our findings bring forth an ionic
      bonding with enhanced stability for the Al6Mg cluster, paired with a surprisingly
      large HOMO-LUMO gap, as would be expected from the magic number of 20 valence
      electrons.

PMID- 27711645
TI  - Understanding molecular self-assembly of a diol compound by considering
      competitive interactions.
AB  - With a combination of scanning tunneling microscopy and density functional
      theory, effects on molecular self-assembly involving two distinct chemical groups
      were investigated. We analyzed the influence of the individual functional units
      in the adsorbate and extracted the dominating contributions to the adsorption
      behaviour. The viability of such a systematic approach to study self-assembled
      structures by considering the interplay between substrate effects and molecular
      design is demonstrated.

PMID- 27711646
TI  - Unusual linear dependency of viscosity with temperature in ionic liquid/water
      mixtures.
AB  - An unusual linear dependency of viscosity with temperature has been observed in
      aqueous solutions of 1-octyl-3-methylimidazolium-based ionic liquids because of
      the ion induced structural transition which leads to the violation of both the
      Stokes-Einstein and fractional Stokes-Einstein equations, suggesting the presence
      of dynamic heterogeneity in the system.

PMID- 27711647
TI  - Interfacial properties of POPC/GDO liquid crystalline nanoparticles deposited on
      anionic and cationic silica surfaces.
AB  - Reversed lipid liquid crystalline nanoparticles (LCNPs) of the cubic micellar
      (I2) phase have high potential in drug delivery applications due to their ability
      to encapsulate both hydrophobic and hydrophilic drug molecules. Their
      interactions with various interfaces, and the consequences for the particle
      structure and integrity, are essential considerations in their effectiveness as
      drug delivery vehicles. Here, we have studied LCNPs formed of equal fractions of
      1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and glycerol dioleate in the
      presence of different fractions of the stabilizer Polysorbate 80. We have used a
      combination of ellipsometry, quartz crystal microbalance with dissipation
      monitoring and neutron reflectometry to reveal the structure and composition of
      the adsorbed layer on both anionic silica and cationic
      (aminopropyltriethoxysilane) silanized surfaces. For both types of surfaces,
      there is a spread near-surface layer comprising lipid and polymer as well as a
      sparse coverage of intact particles. The composition of the near-surface layer is
      very close to that of the particles, in contrast to the lipid bilayer observed
      with related systems. The interaction is stronger for cationic than anionic
      surfaces, which is rationalized in terms of the negative zeta potential of the
      LCNPs. The work shows that the attachment of and spreading from LCNPs is
      influenced by the properties of the surface, the internal structure, composition
      and stability of the particles as well as the nature of the stabilizer.

PMID- 27711648
TI  - Mechanistic insights into lithium ion battery electrolyte degradation - a
      quantitative NMR study.
AB  - The changes in electrolyte composition on the molecular level and the reaction
      mechanisms of electrolyte degradation upon thermal aging are monitored by
      quantitative NMR spectroscopy, revealing similar rates of degradation for
      pristine and already aged electrolytes. The data analysis is not in favor of an
      autocatalytic reaction mechanism based on OPF3 but rather indicates that the
      degradation of LiPF6 in carbonate based solvents proceeds via a complex sequence
      of "linear" reactions rather than a cyclic reaction pattern which is determined
      by the amount of water present in the samples. All investigated electrolytes are
      reasonably stable at temperatures of up to 60  degrees C in the presence of minor
      amounts or absence of water hence indicating that chemical instability of
      electrolyte components against water is decisive for degradation and an increase
      in temperature ("thermal aging") just accelerates the degradation impact of
      water.

PMID- 27711649
TI  - Probing the potential of halogen-free superhalogen anions as effective
      electrolytes of Li-ion batteries: a theoretical prospect from combined ab initio
      and DFT studies.
AB  - The potential of 23 superhalogen anions of halogen-free structures as high
      performance electrolytes of Li-ion batteries is theoretically explored here.
      According to high-level ab initio results at the CCSD(T) level, eight candidates,
      obeying the Wade-Mingos rule, should be capable of forming electrolytes, which
      are better than the currently used commercial products. When comparing different
      methods, MP2 was found to be in good agreement with CCSD(T) in the calculation of
      DeltaELi+ and DeltaEH2O, which are parameters describing the performance of
      potential electrolytes. Thus, MP2 represents a good choice for such calculations,
      particularly for large potential electrolyte systems wherein CCSD(T) calculations
      are actually impractical. The five functionals selected here (omegaB97XD, B2GP
      PLYP, B2K-PLYP, B2T-PLYP and B3LYP) are also capable of reproducing the
      variational trends of the relative values of different structures at the CCSD(T)
      level. However, the actual DFT values of DeltaELi+ are usually different from
      those of CCSD(T) by more than 1 eV. These significant deviations may be a problem
      when accurate DeltaELi+ values are required.

PMID- 27711650
TI  - Scaling of excitons in graphene nanodots.
AB  - The binding energy of an exciton in a semiconductor or an insulator is known to
      scale linearly with epsilonr-2, where epsilonr is its dielectric constant. In
      graphene however, since the kinetic energy scales linearly with the wave number
      instead of its square, the exciton binding energy is thus expected to scale with
      epsilonr-1. In this work we make use of the configuration interaction approach to
      study the properties of excitons in graphene nanodots embedded in various
      dielectric environments. With tens of million configurations taken into account
      in the calculation, we find that the exciton binding energy can be well described
      by a single scaling rule in which the scaling factor is found to vary with the
      dimension of the nanodots as well as with the on-site interaction parameter,
      which agrees well with a recent experiment. The linear relation of the exciton
      binding energy found with the quasi-particle gap also agrees with the previous
      work on bulk graphene and other two-dimensional materials.

PMID- 27711651
TI  - Fluorescent chemosensors manipulated by dual/triple interplaying sensing
      mechanisms.
AB  - Fluorescence imaging is a powerful approach for noninvasive and real-time
      visualization and tracking of biomolecules and biological processes in living
      systems. The fluorescent chemosensors with dual/triple interplaying sensing
      mechanisms tend to provide diverse fluorescence signals or amplify the response
      signals, which are propitious to simultaneously track multiple analytes or to
      improve the selectivity and sensitivity of the chemosensors. Thus, the
      development of dual/triple sensing mechanism-based chemosensors has attracted
      great interest recently. This review highlights the representative cases of the
      fluorescent chemosensors with dual/triple interplaying sensing mechanisms
      published since 2010, and these chemosensors are classified according to the
      types of the interplaying sensing mechanisms, including ICT-FRET, PET-FRET, PET
      ICT-ESIPT, etc.

PMID- 27711652
TI  - Ethylene decomposition on Ir(111): initial path to graphene formation.
AB  - The complete mechanism behind the thermal decomposition of ethylene (C2H4) on
      Ir(111), which is the first step of graphene growth, is established for the first
      time employing a combination of experimental and theoretical methods. High
      resolution X-ray photoelectron spectroscopy was employed, along with calculations
      of core level binding-energies, to identify the surface species and their
      evolution as the surface temperature is increased. To understand the experimental
      results, we have developed a reaction sequence between the various CnHm species,
      from ethylene to C monomers and dimers, based on ab initio density functional
      calculations of all the energy barriers and the Arrhenius prefactors for the most
      important processes. The resulting temperature evolution of all species obtained
      from the simulated kinetics of ethylene decomposition agrees with photoemission
      measurements. The molecular dissociation mechanism begins with the
      dehydrogenation of ethylene to vinylidene (CH2C), which is then converted to
      acetylene (CHCH) by the removal and addition of an H atom. The C-C bond is then
      broken to form methylidyne (CH), and in the same temperature range a small amount
      of ethylidyne (CH3C) is produced. Finally methylidyne dehydrogenates to produce C
      monomers that are available for the early stage nucleation of the graphene
      islands.

PMID- 27711653
TI  - Tuning the structure and mechanical property of polymer nanocomposites by
      employing anisotropic nanoparticles as netpoints.
AB  - Introducing carbon nanotubes or graphene sheets into polymer matrices has
      received lots of scientific and technological attention. For the first time, we
      report a new kind of polymer nanocomposite (PNC) by means of employing
      anisotropic nanoparticles (NPs) as netpoints (referred to as an end-linked
      system), namely with NPs acting as netpoints to chemically connect the dual end
      groups of each polymer chain to form a network. By taking advantage of this
      strategy, the anisotropic NPs can be uniformly distributed in the polymer matrix,
      with the NPs being separated via the connected polymer chains. And the separation
      distance between NPs, the stress-strain behavior and the dynamic hysteresis loss
      (HL) can be manipulated by varying the temperature and the polymer chain
      flexibility. Meanwhile, the physically mixed system is investigated by changing
      the interaction strength between polymer and NPs, and the temperature. It is
      emphasized that compared to the physically mixed system, the end-linked system
      which employs carbon nanotubes or graphene as netpoints possesses good thermal
      stability because of its thermodynamically stable morphology, exhibiting both
      excellent static and dynamic mechanical properties. These results help us to
      design and fabricate high performance and multi-functional PNCs filled with
      carbon nanotubes or graphene, facilitating the potentially large industrial
      application of these nanomaterials.

PMID- 27711654
TI  - Facile solvothermal synthesis of a high-efficiency CNNs/Ag/AgCl plasmonic
      photocatalyst.
AB  - A CNNs/Ag/AgCl (defined as CNAAC) plasmonic photocatalyst with efficient
      photocatalytic degradation ability was obtained by depositing Ag/AgCl
      nanoparticles on g-C3N4 nanosheets (CNNS). Methyl orange (MO) and rhodamine B
      (RhB) were selected to evaluate the photocatalytic degradation performance of the
      as-synthesized CNAAC plasmonic photocatalysts. Among all of the prepared CNAAC
      plasmonic photocatalysts, CNAAC4 showed the most efficient photocatalytic
      degradation performance under visible light. Recycling experiments were also
      performed to confirm the superior stability of CNAAC4. The synergistic effect
      between the surface plasmon resonance effect (SPR) of the Ag nanoparticles and
      the steady heterojunction of CNNs-Ag/AgCl may mainly contribute to the enhanced
      photocatalytic activity and high stability of CNAAC.

PMID- 27711655
TI  - Shuttle inhibition by chemical adsorption of lithium polysulfides in B and N co
      doped graphene for Li-S batteries.
AB  - The advance of lithium sulfur batteries is now greatly restricted by the fast
      capacity fading induced by shuttle effect. Using first-principles calculations,
      various vacancies, N doping, and B,N co-doping in graphene sheets have been
      systematically explored for lithium polysufides entrapped in Li-S batteries. The
      LiS, LiC, LiN and SB bonds and Hirshfeld charges in the Li2S6 adsorbed defective
      graphene systems have been analyzed to understand the intrinsic mechanism of
      retaining lithium polysulfides in these systems. Total and local densities of
      states analyses elucidate the strongest adsorption sites among the N and B-N co
      doped graphene systems. The overall electrochemical performance of Li-S batteries
      varies with the types of defects in graphene. Among the defective graphene
      systems, only the reconstructed pyrrole-like vacancy is effective for retaining
      lithium polysulfides. N doping induces a strong LiN interaction in the defective
      graphene systems, in which the pyrrolic N rather than the pyridinic N plays a
      dominant role in trapping of lithium polysulfides. The shuttle effect can be
      further depressed via pyrrolic B,N co-doped defective graphene materials,
      especially the G-B-N-hex system with extremely strong adsorption of lithium
      polysulfides (4-5 eV), and simultaneous contribution from the strong LiN and SB
      interactions.

PMID- 27711656
TI  - Response to Comment on T. Stauch, A. Dreuw, "Stiff-stilbene photoswitch ruptures
      bonds not by pulling but by local heating", Phys. Chem. Chem. Phys., 2016, 18,
      15848.

PMID- 27711657
TI  - The origin of cooperative solubilisation by hydrotropes.
AB  - The signature of hydrotropic solubilisation is the sigmoidal solubility curve;
      when plotted against hydrotrope concentration, solubility increases suddenly
      after the minimum hydrotrope concentration (MHC), and reaches a plateau at higher
      hydrotrope concentrations. This sigmoidal curve is characteristic of cooperative
      phenomena, yet the true molecular basis of hydrotropic cooperativity has long
      remained unclear. Here we develop a theory, derived from the first principles of
      statistical thermodynamics using partially-open ensembles, to identify the origin
      of hydrophobic cooperativity. Our theory bears a close resemblance to the
      cooperative binding model used for protein-ligand binding. The cause of
      cooperativity is the enhancement of the hydrotrope m-body interaction induced by
      the presence of the solute; m can be estimated from the experimental solubility
      data.

PMID- 27711658
TI  - Highly luminescent and stable lyotropic liquid crystals based on a europium beta
      diketonate complex bridged by an ethylammonium cation.
AB  - Soft lanthanide luminescent materials are impressive because of their tunable and
      self-assembling characteristics, which make them an attractive emerging materials
      field of research. In this report, novel luminescent lyotropic liquid crystals
      (LLCs) with four different mesophases have been fabricated by a protic ionic
      liquid (IL) based europium beta-diketonate complex EA[Eu(TTA)4] (EA =
      ethylammonium, TTA = 2-thenoyltrifluoro-acetone) and an amphiphilic block
      copolymer (Pluronic P123). The protic IL, ethylammonium nitrate (EAN), was used
      as both the solvent and linkage to stabilize the doped complexes. Analyses by
      single-crystal X-ray diffraction for EA[Eu(TTA)4] and Fourier transform infrared
      spectroscopy for the LLC materials reveal convincingly that the ethylammonium
      cations establish an effective connection with both the carbonyl group of the
      beta-diketonate ligand and the EO blocks of the amphiphilic block copolymer P123
      via strong hydrogen bonding interactions. Due to this, an extremely long decay
      time of the excited state is obtained in EA[Eu(TTA)4] and excellent
      photostability of the luminescent LLCs could be achieved. The long-period ordered
      structures of the luminescent LLCs have been investigated by small-angle X-ray
      scattering measurements and the best luminescence performance was found in the
      most organized mesophase. Noteworthy, the LLCs could yield an effective confining
      effect on the europium complex accompanied by a sizeable elongation of the
      excited-state lifetime and an enhancement of the energy transfer efficiency,
      which reaches a remarkably high value of 52.6%. More importantly, the modulated
      luminescence properties observed in the four mesophase structures offer the
      potential and powerful possibility for these unique composite LLCs to be used in
      the fabrication of soft luminescent materials with tunable functions.

PMID- 27711659
TI  - Effect of alkyl chain functionalization of ionic liquid surfactants on the
      complexation and self-assembling behavior of polyampholyte gelatin in aqueous
      medium.
AB  - The complexation behaviour of an imidazolium based ionic liquid surfactant (ILS)
      3-methyl-1-dodecylimidazolium chloride, [C12mim][Cl], and its amide and ester
      functionalized counterparts 3-(2-(dodecylamino)-2-oxoethyl)-1-methyl-1H-imidazol
      3-ium chloride, [C12Amim][Cl], and 3-methyl-1-dodecyloxycarbonylmethylimidazolium
      chloride, [C12Emim][Cl], with a model protein gelatin (G) in aqueous solution has
      been investigated. Complexation of G with ILSs at the air-solution interface has
      been monitored by tensiometry, whereas complexation and ILS mediated self
      assembly of G-ILS complexes in the bulk have been followed by dynamic light
      scattering (DLS), zeta-potential measurements, conductivity, and fluorescence
      techniques. The morphology of different self-assembled architectures has been
      monitored by scanning electron microscopy (SEM). Different transitions observed
      from various techniques in different concentration regimes of ILSs have been
      assigned to the varying extent of complexation and ILS mediated self-assembly of
      G-ILS complexes. The functionalization of the alkyl chain of the ILS [C12mim][Cl]
      with an amide ([C12Amim][Cl]) or ester ([C12Emim][Cl]) moiety owing to their
      additional hydrogen bonding (H-bonding) ability along with rigidity
      ([C12Amim][Cl]) or flexibility ([C12Emim][Cl]) near the imidazolium head group
      has been found to exert great influence on their complexation with G. This
      influence is fashioned as self-assembled structures of G-ILS complexes into
      discrete large hexagonal sheet-like or near spherical architectures, depending on
      the concentration and type of functionality of the alkyl chain of ILSs. The
      thermodynamic forces behind the complexation and self-assembly processes have
      been monitored by isothermal titration calorimetry (ITC) measurements and are
      discussed in detail. As both the nature of the ILS and protein (charge and
      structure) could affect their interactional behavior, the present results are
      expected to be very useful in deeply understanding the structure-property
      relationship between the nature of the ILS and proteins, which would be of great
      importance in the field of functional soft-materials.

PMID- 27711661
TI  - Ultrafast electronic energy relaxation in a conjugated dendrimer leading to inter
      branch energy redistribution.
AB  - Dendrimers are arrays of coupled chromophores, where the energy of each unit
      depends on its structure and conformation. The light harvesting and energy
      funneling properties are strongly dependent on their highly branched conjugated
      architecture. Herein, the photoexcitation and subsequent ultrafast electronic
      energy relaxation and redistribution of a first generation dendrimer (1) are
      analyzed combining theoretical and experimental studies. Dendrimer 1 consists of
      three linear phenylene-ethynylene (PE) units, or branches, attached in the meta
      position to a central group opening up the possibility of inter-branch energy
      transfer. Excited state dynamics are explored using both time-resolved
      spectroscopy and non-adiabatic excited state molecular dynamics simulations. Our
      results indicate a subpicosecond loss of anisotropy due to an initial excitation
      into several states with different spatial localizations, followed by exciton
      self-trapping on different units. This exciton hops between branches. The absence
      of an energy gradient leads to an ultrafast energy redistribution among
      isoenergetic chromophore units. At long times we observe similar probabilities
      for each branch to retain significant contributions of the transition density of
      the lowest electronic excited-state. The observed unpolarized emission is
      attributed to the contraction of the electronic wavefunction onto a single branch
      with frequent interbranch hops, and not to its delocalization over the whole
      dendrimer.

PMID- 27711660
TI  - Monomer zinc phthalocyanine/upconversion nanoparticle coated with hyaluronic acid
      crosslinked gel as NIR light-activated drug for in vitro photodynamic therapy.
AB  - Carboxyl group modified zinc phthalocyanines (ZnPc) are classic and widely used
      photosensitizers (PSs) in upconversion nanoparticles (UCNPs) mediated
      photodynamic therapy (PDT) for tumor treatment. To improve the PDT activity of
      the complex system of ZnPc and UCNPs, many UCNPs with high red emission intensity
      were design and prepared. ZnPc-(COOH)4 tends to aggregate both in water and under
      physiological conditions, which can sharply decrease its PDT activity. Therefore,
      choosing monomeric COOH groups modified ZnPc as PSs is an alternative way to
      improve their activity. In this manuscript, three zinc(ii) phthalocyanines,
      substituted with 4 (ZnPc-(COOH)4), 8 (ZnPc-(COOH)8) and 16 (ZnPc-(COOH)16) COOH
      groups, were synthesized. A comparison of the results indicated that ZnPc
      (COOH)16 existed in its monomeric form under physiological conditions because of
      its large substituents. Moreover, ZnPc-(COOH)16 showed superior singlet oxygen
      (1O2) generation ability when compared to ZnPc-(COOH)4 and ZnPc-(COOH)8.
      Therefore, we chose ZnPc-(COOH)16 as PSs for absorption on the surface of the
      UCNPs. Then, they were encapsulated by crosslinked methacrylated hyaluronic acid
      (m-HA), which provides active tumor accumulation ability by binding its
      overexpressed receptors on the surface of cancer cells. The resulting
      nanoparticles can be effectively taken up by cancer cells and shows strong near
      infrared (NIR) light triggered PDT in vitro.

PMID- 27711662
TI  - Accurate prediction of bulk properties in hydrogen bonded liquids: amides as case
      studies.
AB  - In this contribution we show that it is possible to build accurate force fields
      for small organic molecules allowing the reliable reproduction of a large panel
      of bulk properties, which are seldom addressed in the same context. Starting from
      the results obtained in recent studies, we developed a protocol for charge
      estimation and virtual site generation for the amide class of molecules. The
      parametrization of electrostatic properties is based on population analysis and
      orbital localization of quantum mechanical computations rooted in density
      functional theory and the polarizable continuum model, without any additional
      external information. The new protocol, coupled to other recent studies in our
      group targeted at an accurate fitting of internal degrees of freedom, makes
      available a method for building force fields from scratch (excluding for the
      moment intermolecular van der Waals interactions) with focus on reproducing the
      structure and dynamics of hydrogen bonded liquids, yielding results that are in
      line or better than those delivered by current general force fields. The approach
      is tested on the demanding series formed by formamide and its two N-methyl
      derivatives, N-methylformamide and N,N-dimethylformamide. We show that the
      atomistic structure of the liquids arising from classical molecular dynamics (MD)
      simulations employing the new force field is in full agreement with X-ray and
      neutron diffraction experiments and the corresponding spatial distribution
      functions are in remarkable agreement with the results of ab initio MD
      simulations. It is noteworthy that the latter result has never been obtained
      before without using ad hoc (and system dependent) scale factors and that, in
      addition, our parameter-free procedure is able to reproduce static dielectric
      constants over a wide range of values without sacrificing the force field
      accuracy with respect to other observables. Finally, we are able to explain the
      trend of static dielectric constants followed by the three amides in terms of
      properties obtained from the simulations, namely hydrogen bond patterns and
      reorientational lifetimes.

PMID- 27711663
TI  - First-principles electronic structure calculations for the whole spinel oxide
      solid solution range MnxCo3-xO4 (0 <= x <= 3) and their comparison with
      experimental data.
AB  - Transition metal spinel oxides have recently been suggested for the creation of
      efficient photovoltaic cells or photocatalysts. These compounds can be easily
      tuned by doping to adapt their electronic or magnetic properties. However, their
      cation distribution is very complex and band structures are still a subject of
      controversy. We propose a complete density functional theory investigation of
      MnxCo3-xO4 compounds, using different approximations in order to explain the
      variation of these properties as a function of composition (for 0 <= x <= 3) and
      determine the electronic structure over the whole solid solution range. A
      detailed study of their atomic structure, magnetic properties and electronic
      structure is given and compared with experimental data. The unit cell volume
      calculated for each composition is in agreement with the volume obtained
      experimentally in ceramics, while a cubic-to-tetragonal structural transition is
      predicted at x = 2.0. An antiferromagnetic to ferrimagnetic behavior is observed
      at the lowest ordering temperature depending on the composition. The band gap,
      deduced from our band structure calculations, strongly decreases upon doping of
      the end members Co3O4 and Mn3O4, but is partly restored by the tetragonal
      distortion. A direct band gap, close to 0.5-0.8 eV, is calculated for 0.25 <= x
      <= 2.25, justified by inter-metal transitions from Mn ions on octahedral sites.

PMID- 27711664
TI  - Application of the dielectric-dependent screened exchange potential approach to
      organic photocell materials.
AB  - This paper discusses the fundamental features of the dielectric-dependent
      screened exchange potential approach for organic molecules and photocell
      materials. The energy difference (gap) between the highest occupied molecular
      orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) is a key factor
      when designing organic photocell materials. The magnitude of this energy gap
      strongly depends on the ratio of the Hartree-Fock (HF) exchange term combined
      with hybrid density functional theory (DFT) functionals. In ordinary hybrid DFT
      functionals, the HF exchange term ratio is often determined empirically and a
      constant value is employed for all materials. Conversely, the dielectric
      dependent exchange potential approach employs a system-dependent value for this
      parameter, which is proportional to the inverse of the dielectric constant. The
      organic materials examined in this paper take different dielectric constant
      values according to their material types and unit lengths; therefore, their HF
      exchange ratios are also different. This paper discusses the relationship between
      the energy gaps, the dielectric constants, and the HF exchange ratios in the
      dielectric-dependent screened exchange potential approach. For a series of acene
      type compounds, it was found that the HOMO-LUMO gap decreased when their
      conjugation systems are extended. The dielectric-dependent screened exchange
      potential approach demonstrated that the values of the dielectric constants of
      the compounds increased; consequently, the HF exchange ratio decreased. Similar
      results were obtained for a series of thiophene-based donor molecules. The
      calculated values were compared with those obtained via experimental
      measurements. We found that although the theoretical calculations of the HOMO
      LUMO gap usually overestimate experimental optical gaps, a better agreement
      between the experimental and calculated values can be obtained if we correct for
      the exciton binding energy.

PMID- 27711665
TI  - Recent progress in the design and applications of fluorescence probes containing
      crown ethers.
AB  - Crown ethers, discovered by the winner of the Nobel Prize Charles Pedersen, are
      cyclic chemical compounds that consist of a ring or multiple rings containing
      several ether groups that are capable of binding alkali ions. A smart fluorescent
      probe containing a crown ether moiety could be developed as a sensor for metal
      ions, anions and other bio-molecules and be further applied to monitor the
      relevant biological process in vivo. This review highlights recent advances which
      can be divided into seven parts: (i) fluorescent probes containing a simple crown
      ether or an aza-crown ether structure; (ii) fluorescent probes containing an
      azathia crown ether; (iii) fluorescent probes containing a cryptand; (iv)
      fluorescent probes containing two or more binding sites; (v) crown ether
      derivatives-metal complex assisted chemosensing of bioactive species; (vi) crown
      ether-based chemosensors for bioactive molecular detection; and (vii) efforts to
      improve biological relevance.

PMID- 27711666
TI  - Distinctive electron transport on pyridine-linked molecular junctions with narrow
      monolayer graphene nanoribbon electrodes compared with metal electrodes and
      graphene electrodes.
AB  - The electrodes in the molecular devices are essential for creating functional
      organic electronic devices. We investigate theoretically the pyridine-terminated
      molecule - 4,4'-bipyridyl attached to the narrow monolayer zigzag graphene
      nanoribbon electrodes, compared to the metal (Au, Ag and Cu) and 2D graphene
      electrodes. Results show that this zigzag graphene nanoribbon-based junction
      shows excellent electron transport performances. It possesses great transmission
      at the fermi level due to the strongest delocalization of the electronic state.
      The coupling of the dominant molecular orbital to the ZGNR electrodes is much
      stronger than that to the metal electrodes due to a higher contributing
      proportion of PDOS on N atoms in the molecule at the fermi level. Also the
      molecular orbital couples more strongly to the ZGNR electrodes than the graphene
      electrodes because of a larger device density of state around the fermi level.
      Moreover, the different molecule-electrode coupling among these metal-based
      devices stems from the different proportion of density of d-states of the
      electrodes at the fermi level. In addition, the device with the narrow ZGNR
      electrodes exhibits the NDR effect unexpectedly.

PMID- 27711667
TI  - Gels with sense: supramolecular materials that respond to heat, light and sound.
AB  - Advances in the field of supramolecular chemistry have made it possible, in many
      situations, to reliably engineer soft materials to address a specific
      technological problem. Particularly exciting are "smart" gels that undergo
      reversible physical changes on exposure to remote, non-invasive environmental
      stimuli. This review explores the development of gels which are transformed by
      heat, light and ultrasound, as well as other mechanical inputs, applied voltages
      and magnetic fields. Focusing on small-molecule gelators, but with reference to
      organic polymers and metal-organic systems, we examine how the structures of
      gelator assemblies influence the physical and chemical mechanisms leading to
      thermo-, photo- and mechano-switchable behaviour. In addition, we evaluate how
      the unique and versatile properties of smart materials may be exploited in a wide
      range of applications, including catalysis, crystal growth, ion sensing, drug
      delivery, data storage and biomaterial replacement.

PMID- 27711669
TI  - Adsorption dynamics and rate assessment of volatile organic compounds in active
      carbon.
AB  - In this paper, an investigation was presented about terahertz time-domain
      spectroscopy (THz-TDS) as a novel tool for the characterization of the dynamic
      adsorption rate of volatile organic compounds, including isooctane, ethanol, and
      butyl acetate, in the pores of active carbon. The THz-TDS peak intensity (EP) was
      extracted and corresponded to the measurement time frames. By analyzing EP with
      time, the entire process could be divided into three physical parts including
      volatilization, adsorption and stabilization so that the adsorption dynamics
      could be clearly identified. In addition, based on the pseudo-second-order
      kinetic model and the relationship between EP and time in the adsorption process,
      a mathematical model was built in terms of the adsorbed rate parameter and the
      THz parameter. Consequently, the adsorption rate of isooctane, ethanol, and butyl
      acetate could be assessed by the THz measurement, indicating that THz
      spectroscopy could be used as a promising selection tool to monitor the
      adsorption dynamics and evaluate adsorption efficiency in the recovery of
      pollutants.

PMID- 27711670
TI  - Direct simulation of electron transfer in the cobalt hexammine(ii/iii) self
      exchange reaction.
AB  - We present an atomistic simulation of the cobalt hexammine(ii/iii) self-exchange
      reaction using path integral (PI) methods. We construct a simple force field for
      the system in its reactant state that includes parameters for both atom-atom
      interactions, and interactions with an explicit transferring electron represented
      in the PI framework. We then calculate the outer sphere free energy barrier due
      to solvent reorganization from a PI molecular dynamics simulation and we obtain
      the dynamic transmission coefficient using ring polymer molecular dynamics.
      Combining these calculated values with literature values for the inner sphere
      reorganization energy, we obtain a reaction rate in good agreement with
      experimental measurements. The protocol introduced here circumvents the need for
      complex, system-specific force field parameterization along an assumed reaction
      coordinate making it sufficiently accurate, efficient, and broadly applicable to
      the study of both adiabatic and nonadiabatic charge transfer reactions in
      transition metal complexes.

PMID- 27711668
TI  - Synthesis, characterization, biological activity, DNA and BSA binding study:
      novel copper(ii) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate.
AB  - A serie of novel square pyramidal copper(ii) complexes [Cu(L)2H2O] (3a-d) with
      O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3
      methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4'-hydroxy-3'-methoxyphenyl)vinyl
      2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by
      spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The
      antimicrobial activity was estimated by the determination of the minimal
      inhibitory concentration (MIC) using the broth microdilution method. The most
      active antibacterial compounds were 3c and 3d, while the best antifungal activity
      was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL-1) was
      measured for 3c against Proteus mirabilis. The cytotoxic activity was tested
      using the MTT method on human epithelial carcinoma HeLa cells, human lung
      carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed
      extremely better cytotoxic activity compared to cisplatin at all tested
      concentrations. Compound 3d expressed the best activity against all tested cell
      lines with IC50 values ranging from 7.45 to 7.91 MUg mL-1. The type of cell death
      and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry.
      Both compounds induced apoptosis and S phase cell cycle arrest. The interactions
      between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA)
      were investigated by the fluorescence spectroscopic method. Competitive
      experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity
      to displace EB from the EB-DNA complex through intercalation suggesting strong
      competition with EB [Ksv = (1.4 +/- 0.2) and (2.9 +/- 0.1) * 104 M-1,
      respectively]. Ksv values indicate that these complexes bind to DNA covalently
      and non-covalently. The achieved results in the fluorescence titration of BSA
      with 3d and 3e [Ka = (2.9 +/- 0.2) * 106 and (2.5 +/- 0.2) * 105 M, respectively]
      showed that the fluorescence quenching of BSA is a result of the formation of the
      3d- and 3e-BSA complexes. The obtained Ka values are high enough to ensure that a
      significant amount of 3d and 3e gets transported and distributed through the
      cells.

PMID- 27711671
TI  - Axial coordination and electronic structure of diatomic NO, CO, and O2 molecules
      adsorbed onto Co-tetraphenylporphyrin on Au(111), Ag(111), and Cu(111): a density
      functional theory study.
AB  - Based on density functional theory calculations, we investigated the axial
      bindings of diatomic molecules (NO, CO, and O2) to metalloporphyrins and their
      spin switching behaviors. These binding reactions provide the ways to control
      molecular states and spins in metalloporphyrin systems that can be used in bio
      sensing and spintronic applications. To microscopically understand the non
      trivial axial binding structures and spin-switching behaviors of diatomic
      molecules (NO, CO, and O2) adsorbed onto Co-tetraphenylporphyrin (CoTPP), we
      performed spin-polarized density functional theory (DFT) calculations for various
      CoTPP systems on Au(111), Ag(111), and Cu(111) substrates. We also systematically
      evaluated the effects of van der Waals and Hubbard U corrections by directly
      comparing the electronic structure with the results of scanning tunnelling
      microscopy. From the calculation results, we have found that a NO molecule,
      almost 60 degrees  tilted away from the axial direction, is coordinated with
      CoTPP with a binding energy of 1.2-1.7 eV depending on substrates, and the spin
      state of CoTPP is completely switched off due to the charge transfer from NO to
      CoTPP. On the other hand, CO and O2 molecules rather weakly interact with a
      binding energy of 0.4-0.8 eV, and a spin polarization of ~1MUB is still present
      at CoTPP. A CO molecule is expected to be almost straightly coordinated along the
      axial direction of CoTPP, but O2 is tilted similarly to the NO case. Regarding
      the substrate effects, we have found that there is noticeable charge transfer
      from Ag(111) and Cu(111) to CoTPP, but no significant charge transfer from
      Au(111) to CoTPP. These findings of the axial coordination and spin states for
      NO, CO, and O2 adsorbed CoTPP systems will be useful for understanding bio
      sensing mechanisms and designing molecular spintronic systems.

PMID- 27711672
TI  - Two-photon excitation nanoparticles for photodynamic therapy.
AB  - Two-photon excitation (TPE) nanoparticle-based photosensitizers (PSs) that
      combine the advantages of TPE and nanotechnology have emerged as attractive
      therapeutic agents for near-infrared red (NIR) light excited photodynamic therapy
      (PDT) for cancer treatment. TPE PDT is characterized by nonlinear absorption of
      two relatively low-energy photons of NIR light with the resulting emission of
      high-energy visible light. This high-energy light can sensitize oxygen to produce
      cytotoxic reactive oxygen species (ROS) and singlet oxygen (1O2) which can kill
      cancer cells. The long-wavelength light used to excite TPE NPs allows for deeper
      tissue penetration to achieve efficient PDT of deep-seated tumors. Moreover, TPE
      nanoparticles normally have large two-photon absorption (TPA) cross-sections,
      which hold great potential as efficient two-photon donors in PDT. In this review,
      we will summarize the recent advances made in the development of TPE
      nanoparticles for cancer PDT. Five different TPE nanoparticles, including quantum
      dots (QDs), carbon nanomaterials, silica nanoparticles, gold nanomaterials, and
      polymer nanoparticles, are summarized in detail, and the existing challenges as
      well as the future perspectives are also discussed.

PMID- 27711674
TI  - Structure and Li+ ion transport in a mixed carbonate/LiPF6 electrolyte near
      graphite electrode surfaces: a molecular dynamics study.
AB  - Electrolyte and electrode materials used in lithium-ion batteries have been
      studied separately to a great extent, however the structural and dynamical
      properties of the electrolyte-electrode interface still remain largely unexplored
      despite its critical role in governing battery performance. Using molecular
      dynamics simulations, we examine the structural reorganization of solvent
      molecules (cyclic ethylene carbonate : linear dimethyl carbonate 1 : 1 molar
      ratio doped with 1 M LiPF6) in the vicinity of graphite electrodes with varying
      surface charge densities (sigma). The interfacial structure is found to be
      sensitive to the molecular geometry and polarity of each solvent molecule as well
      as the surface structure and charge distribution of the negative electrode. We
      also evaluated the potential difference across the electrolyte-electrode
      interface, which exhibits a nearly linear variation with respect to sigma up
      until the onset of Li+ ion accumulation onto the graphite edges from the
      electrolyte. In addition, well-tempered metadynamics simulations are employed to
      predict the free-energy barriers to Li+ ion transport through the relatively
      dense interfacial layer, along with analysis of the Li+ solvation sheath
      structure. Quantitative analysis of the molecular arrangements at the electrolyte
      electrode interface will help better understand and describe electrolyte
      decomposition, especially in the early stages of solid-electrolyte-interphase
      (SEI) formation. Moreover, the computational framework presented in this work
      offers a means to explore the effects of solvent composition, electrode surface
      modification, and operating temperature on the interfacial structure and
      properties, which may further assist in efforts to engineer the electrolyte
      electrode interface leading to a SEI layer that optimizes battery performance.

PMID- 27711673
TI  - Metal-organic frameworks as competitive materials for non-linear optics.
AB  - The last five years have witnessed a huge breakthrough in the creation and the
      study of the properties of a new class of compounds - metamaterials. The next
      stage of this technological revolution will be the development of active,
      controllable, and non-linear metamaterials, surpassing natural media as platforms
      for optical data processing and quantum information applications. However,
      scientists are constantly faced with the need to find new methods that can ensure
      the formation of quantum and non-linear metamaterials with higher resolution. One
      such method of producing metamaterials in the future, which will provide
      scalability and availability, is chemical synthesis. Meanwhile, the chemical
      synthesis of organized 3D structures with a period of a few nanometers and a size
      of up to a few millimeters is not an easy task and is yet to be resolved. The
      most promising avenue seems to be the use of highly porous structures based on
      metal-organic frameworks that have demonstrated their unique properties in the
      field of non-linear optics (NLO) over the past three years. Thus, the aim of this
      review is to examine current progress and the possibilities of using metal
      organic frameworks in the field of non-linear optics as chemically obtained
      metamaterials of the future. The review begins by presenting the theoretical
      principles of physical phenomena represented by mathematical descriptions for
      clarity. Major attention is paid to the second harmonic generation (SHG) effect.
      In this section we compare inorganic single crystals, which are most commonly
      used to study the effect in question, to organic materials, which also possess
      the required properties. Based on these data, we present a rationale for the
      possibility of studying the non-linear optical properties of metal-organic
      structures as well as describing the use of synthetic approaches and the
      difficulties associated with them. The second part of the review explicitly
      acquaints the reader with a new class of materials which successfully combines
      the positive properties of organic and inorganic materials. Using recently
      synthesized metal-organic frameworks and coordination polymers in the field of
      non-linear optics as an example, we consider synthetic approaches used for
      obtaining materials with desired properties and the factors to be considered in
      this case. Finally, probable trends towards improving the quality of the
      synthesized materials with regards to their further use in the field of non
      linear optical effects are described.

PMID- 27711675
TI  - Mobility and association of ions in aqueous solutions: the case of imidazolium
      based ionic liquids.
AB  - The mobility and the mechanism of ion pairing of 1,1 electrolytes in aqueous
      solutions were investigated systematically on nine imidazolium based ionic
      liquids (ILs) from 1-methylimidazolium chloride, [MIM][Cl], to 1-dodecyl-3
      methylimidazolium chloride, [1,3-DoMIM][Cl], with two isomers 1,2
      dimethylimidazolium chloride, [1,2-MMIM][Cl], and 1,3-dimethylimidazolium
      chloride, [1,3-MMIM][Cl]. Molecular dynamics (MD) simulations, statistical
      mechanics calculations in the framework of the integral equation theory using one
      dimensional (1D-) and three-dimensional (3D-) reference interaction site model
      (RISM) approaches as well as conductivity measurements were applied. From
      experiment and MD simulations it was found that the mobility/diffusion
      coefficients of cations in the limit of infinite dilution decrease with an
      increasing length of the cation alkyl chain, but not linearly. The aggregation
      tendency of cations with long alkyl chains at higher IL concentrations impedes
      their diffusivity. Binding free energies of imidazolium cations with the chloride
      anion estimated by RISM calculations, MD simulations and experiments reveal that
      the association of investigated ILs as model 1,1 electrolytes in water solutions
      is weak but evidently dependent on the molecular structure (alkyl chain length),
      which also strongly affects the mobility of cations.

PMID- 27711676
TI  - Surface and shape modification of mackinawite (FeS) nanocrystals by cysteine
      adsorption: a first-principles DFT-D2 study.
AB  - The control of nanoparticle shape offers promise for improving catalytic activity
      and selectivity through optimization of the structure of the catalytically active
      site. Here, we have employed density functional theory calculations with a
      correction for the long-range interactions (DFT-D2) to investigate the effect of
      adsorption of the amino acid cysteine on the {001}, {011}, {100}, and {111}
      surfaces of mackinawite, which are commonly found in FeS nanoparticles. We have
      calculated the surface energies and adsorption energies for all the surfaces
      considered, and compared the surface energies of the pure and adsorbed systems.
      Based on the calculated surface energies, we have simulated the thermodynamic
      crystal morphology of the pure and cysteine-modified FeS nanoparticles using
      Wulff's construction. The strength of cysteine adsorption is found to be related
      to the stability of different surfaces, where it adsorbs most strongly onto the
      least stable FeS{111} surface via bidentate Fe-S and Fe-N chemical bonds and most
      weakly onto the most stable FeS{001} surface via hydrogen-bonded interactions;
      the adsorption energy decreases in the order {111} > {100} > {011} > {001}. We
      demonstrate that the stronger binding of the cysteine to the {011}, {100}, and
      {111} surfaces rather than to the {001} facet results in shape modulation of the
      FeS nanoparticles, with the reactive surfaces more expressed in the thermodynamic
      crystal morphology compared to the unmodified FeS crystals. Information regarding
      the structural parameters, electronic structures and vibrational frequency
      assignments of the cysteine-FeS complexes is also presented.

PMID- 27711677
TI  - Rapid acquisition of wideline MAS solid-state NMR spectra with fast MAS, proton
      detection, and dipolar HMQC pulse sequences.
AB  - The solid-state NMR spectra of many NMR active elements are often extremely broad
      due to the presence of chemical shift anisotropy (CSA) and/or the quadrupolar
      interaction (for nuclei with spin I > 1/2). These NMR interactions often give
      rise to wideline solid-state NMR spectra which can span hundreds of kHz or
      several MHz. Here we demonstrate that by using fast MAS, proton detection and
      dipolar hetero-nuclear multiple-quantum (D-HMQC) pulse sequences, it is possible
      to rapidly acquire 2D spectra which correlate 1H chemical shifts to the
      indirectly detected wideline MAS powder patterns of dipolar coupled hetero
      nuclei. The D-HMQC pulse sequence enables broadband excitation of the wideline
      hetero-nuclear NMR spectrum and provides higher sensitivity by detecting the
      narrower and more sensitive 1H NMR signal. This approach is demonstrated for the
      rapid acquisition of 2D 1H detected 195Pt solid-state NMR spectra of cisplatin
      and transplatin and the 71Ga solid-state NMR spectrum of a self-assembled Ga
      coordination polymer of unconfirmed structure. This approach should be broadly
      applicable for the rapid acquisition of wideline MAS solid-state NMR spectra of
      moderately abundant NMR nuclei.

PMID- 27711678
TI  - Investigation of reactivity and structure formation in a K-Te-U oxo-system under
      high-temperature/high-pressure conditions.
AB  - The high-temperature/high-pressure treatment of the K-Te-U oxo-family at 1100 
      degrees C and 3.5 GPa results in the crystallization of a series of novel uranyl
      tellurium compounds, K2[(UO2)3(TeIVO3)4], K2[(UO2)TeO14], alpha-K2[(UO2)TeVIO5]
      and beta-K2[(UO2)TeVIO5]. In contrast to most of the reported uranyl compounds
      which are favorable in layered structures, we found that under extreme
      conditions, the potassium uranyl oxo-tellurium compounds preferably crystallized
      in three-dimensional (3D) framework structures with complex topologies. Anion
      topology analysis indicates that the 3D uranyl tellurite anionic framework
      observed in K2[(UO2)3(TeIVO3)4] is attributable to the additional linkages of
      TeO3 polyhedra connecting with TeO4 disphenoids from the neighboring U-Te layers.
      The structure of K2[(UO2)TeO14] can be described based on [UTe6O26]22- clusters,
      where six TeO5 polyhedra enclose a hexagonal cavity in which a UO8 polyhedron is
      located. The [UTe6O26]22- clusters are further linked by TeO5 square pyramids to
      form the 3D network. Similar to uranyl tellurates, both alpha-K2[(UO2)TeVIO5] and
      beta-K2[(UO2)TeVIO5] contain TeO6 octahedra which share a common face to form a
      dimeric Te2O10 unit. However, in alpha-K2[(UO2)TeVIO5], these Te2O10 units
      connect with UO6 tetragonal bipyramids to form a 3D structural framework, while
      in beta-K2[(UO2)TeVIO5], the same Te2O10 dimers are observed to link with UO7
      pentagonal bipyramids, forming 2D layers. Raman measurements were carried out and
      the vibration bands related to TeIV-O, TeVI-O and UVI-O bonds are discussed.

PMID- 27711679
TI  - Hole-conductor-free perovskite solar cells with carbon counter electrodes based
      on ZnO nanorod arrays.
AB  - A one dimensional nanostructure array has been considered as a successful charge
      transport material for perovskite solar cells (PSCs), because of its large
      internal surface area, superior charge collection efficiency and fast charge
      transport. Herein we demonstrate a ZnO nanorod (NR) array as the electron
      collector in a hole-conductor-free PSC with a carbon counter electrode (CE). A
      relatively low initial power conversion efficiency (PCE) of 5.6% was achieved
      using a 1 MUm long ZnO NR array as an electron collector. However, by
      introduction of a thin TiO2 coating layer on the surface of ZnO via TiCl4
      treatment, the PCE of the cell has been improved to the highest value of 8.24%.
      It is revealed that the performance enhancement of the ZnO/TiO2 NR based PSCs is
      largely attributed to the larger surface area, reduced electron combination, and
      superior electron transport properties.

PMID- 27711680
TI  - Structural, magnetic and magnetocaloric effects in epitaxial
      La0.67Ba0.33Ti0.02Mn0.98O3 ferromagnetic thin films grown on 001-oriented SrTiO3
      substrates.
AB  - Epitaxial La0.67Ba0.33Ti0.02Mn0.98O3 (denoted as LBTMO hereafter) thin films of
      approximately 95 nm thickness were deposited by a pulsed laser deposition
      technique onto SrTiO3 (STO) (001) substrates. High-resolution X-ray diffraction
      (HRXRD) and transmission electron microscopy (TEM) investigations revealed that
      the films are epilayers with a four-fold symmetry around the [001] direction.
      Cross-sectional TEM and the presence of Pendellosung fringes in the XRD profiles
      demonstrate smooth interfaces. The STO substrate induces an in-plane compressive
      strain, which leads to a slight tetragonality of the film structure. The
      epilayers exhibit paramagnetic-to-ferromagnetic phase transitions at the Curie
      temperature TC (286 K), close to room temperature. The magnetization easy axis
      lies in the film plane along the [100] direction of the (001) substrate. The
      magnetic entropy change (DeltaSM) associated with the second-order magnetic phase
      transition was determined via magnetization measurements in the temperature range
      between 210 and 350 K under different magnetic fields. The relative cooling power
      (RCP) of this film is about 220 J kg-1, somewhat lower than that of bulk Gd (410
      J kg-1) for a 50 kOe field change, making the LBTMO ferromagnetic thin films a
      promising candidate for micro/nanomagnetic refrigeration around room temperature.
      The proposed universal curve provides a simple method for extrapolating DeltaSM
      in a wide range of fields and temperatures, thus confirming the order of the
      magnetic transition in this system. The magnetic entropy (DeltaSM)max around TC
      is proportional to (MU0H/TC)2/3 in agreement with the mean-field theory,
      indicating the existence of long-range ferromagnetic interactions in epitaxial
      LBTMO thin films.

PMID- 27711681
TI  - Tunability of the two-dimensional electron gas at the LaAlO3/SrTiO3 interface by
      strain-induced ferroelectricity.
AB  - The two-dimensional electron gas (2DEG) formed at the interface between two
      insulating materials LaAlO3 (LAO) and SrTiO3 (STO) has recently generated a lot
      of interest. Here, based on first-principles density functional theory
      calculations, we investigate the existence and stability of the 2DEG under the
      application of a biaxial strain on the LAO/STO(001) heterostructure. The
      compressive strain induces ferroelectric (FE) polarization in STO, which allows
      for the tunability of the 2DEG by reversing the STO polarization orientation. We
      show that the formation of the 2DEG is unstable when LAO and STO have the same
      polarization direction. On the other hand, the 2DEG will always form if the two
      polarizations are in the opposite directions regardless of the LAO thickness,
      which is in contrast to the unstrained interface that has a critical thickness
      for stabilizing the 2DEG. We show that the underpinnings of this behavior are due
      to charge passivation and band gap alignment.

PMID- 27711682
TI  - Effects of chemical substitutions on the properties of azacalixphyrins: a first
      principles study.
AB  - Azacalixphyrins are particularly stable macrocycles absorbing light up to the
      near infrared region, which makes them good candidates for applications in a wide
      panel of fields. However, to date, only a very limited number of substituted
      azacalixphyrins are experimentally known. Herein, aiming to drive the synthesis
      towards the most promising substitution patterns, we explore with first
      principles approaches the impact of adding substituents on both the aromaticity
      and absorption spectrum of these macrocycles. Both neutral and dicationic species
      are considered. For the former, we show that the substituents have an impact on
      the relative stabilities of the different tautomers, which can lead to
      significant tuning of the properties. Depending on the electron donating or
      electron attracting character of the chemical groups added at the periphery, the
      first absorption band in the near infrared region can be remarkably red or
      blueshifted, respectively. Our calculations also predict that replacing the
      macrocycle phenyl rings with pyridine rings leads to a more planar structure -
      due to the reduction of the steric stress at the centre - and to more equalised
      bond lengths. This results in an increase of the aromatic strength of the
      macrocycle by ca. 20%, at the cost of a large blueshift of the first absorption
      band. Compared to the neutral forms, the latter dicationic species are found to
      be more aromatic. Flatter and therefore more aromatic macrocycles can also be
      obtained for the neutral species by replacing the peripheral NH2/NH groups with
      OH/O groups/atoms, owing to the interaction between the oxygen lone pairs and the
      vicinal hydrogen atom. It is found that the combination of nitrogenation and
      oxidation allows doubling the aromatic character strength compared to the parent
      compound. This work therefore paves the way to the control of the properties of
      azacalixphyrins by purpose-designed substitutions.

PMID- 27711683
TI  - Counterion-dominating chirality transfer between chiral and achiral
      polyoxometalates.
AB  - We show that chirality transfer from chiral polyoxometalates to achiral
      polyoxometalates can occur in aqueous solution with unexpected selectivity of
      surrounding counterions. In comparison with sodium ions, protonated
      dimethylammonium counterions play a critical role in shortening the inter-cluster
      distance, thus promoting the efficiency of chirality transfer.

PMID- 27711684
TI  - The influence of structural isomerism on fluorescence and organic dye selective
      adsorption in two complexes based on flexible ligands.
AB  - Based on Cd(NO3)2.4H2O and 4,4'-((5-carboxy-1,3-phenylene)bis(oxy))dibenzoic acid
      (H3cpbda), two isomeric coordination polymers,
      {[Cd1.5(cpbda)(bpa)(H2O)2].1.5H2O}n (1), [Cd(H2cpbda)2(bpa)0.5(H2O)]n (2), were
      synthesized by using different solvent-systems. The complexes were characterized
      by single-crystal X-ray diffraction, IR spectroscopy, powder X-ray diffraction,
      and thermogravimetric analysis. Owing to the obvious structural difference
      between the two isomeric complexes, the further fluorescence sensing and dye
      selection and adsorption were investigated. The 3D tight stacking structure of 1
      strengthened the fluorescence emission and the loose 2D layer structure of 2
      generated the active selection and adsorption of the Malachite Green Oxalate
      (MGO) dye.

PMID- 27711686
TI  - Observation of isolated ionic liquid cations and water molecules in an inert
      solvent.
AB  - 1-Octyl-3-methyl imidazolium halides ([OMIM]I and [OMIM]Cl) were loaded on top of
      CCl4, and an in situ inclusion process was monitored from the CCl4 phase as time
      elapses by infrared absorption spectroscopy. Absorption from the bands
      corresponding to the C(2)-H and C(4,5)-H stretch modes in the imidazolium cation
      was reduced significantly compared to the bulk IL spectra. This indicates that
      (1) the [OMIM] cation exists in CCl4 as a monomer, dissociated from the anion and
      other cations, and (2) hydrogen bonding between the anion and the cation
      increases the dipole strength of the CH moieties in the imidazolium ring. [OMIM]I
      was found to transfer into the CCl4 phase much faster than [OMIM]Cl, and this
      instigated us to compare the transfer of aqueous solutions of ionic liquids, 1
      butyl-3-methyl imidazolium halides ([BMIM]I and [BMIM]Cl) into the CCl4 matrix.
      Not only [BMIM]I but also water molecules transferred faster compared to those in
      the [BMIM]Cl aqueous solution. Water molecules in CCl4 were shown to form
      clusters in [BMIM]I; presumably, I- anions work as nucleation centers of water
      clusters.

PMID- 27711685
TI  - Self-assembly of like-charged nanoparticles into Voronoi diagrams.
AB  - The self-assembly of nanoscopic building blocks into higher order macroscopic
      patterns is one possible approach for the bottom-up fabrication of complex
      functional systems. Macroscopic pattern formation, in general, is determined by
      the reaction and diffusion of ions and molecules. In some cases macroscopic
      patterns emerge from diffusion and interactions existing between nanoscopic or
      microscopic building blocks. In systems where the distribution of the interaction
      determining species is influenced by the presence of a diffusion barrier, the
      evolving macroscopic patterns will be determined by the spatiotemporal evolution
      of the building blocks. Here we show that a macroscopic pattern can be generated
      by the spatiotemporally controlled aggregation of like-charged carboxyl
      terminated gold nanoparticles in a hydrogel, where clustering is induced by the
      screening effect of the sodium ions that diffuse in a hydrogel. Diffusion fronts
      of the sodium ions and the induced nanoparticle aggregation generate Voronoi
      diagrams, where the Voronoi cells consist of aggregated nanoparticles and their
      edges are aggregation-free and nanoparticle-free zones. We also developed a
      simple aggregation-diffusion model to adequately describe the evolution of the
      experimentally observed Voronoi patterns.

PMID- 27711687
TI  - Lowered phase transition temperature and excellent solar heat shielding
      properties of well-crystallized VO2 by W doping.
AB  - Monoclinic VO2 (M) is a key material for energy-efficient smart window
      applications. Fine crystalline VO2 particles with an ambient phase transition
      temperature are urgently required to achieve excellent properties including high
      luminous transmittance and solar heat shielding ability. Moreover, the anti
      oxidation ability is regarded as a significant factor which determines the
      lifetime of VO2-based products. In this paper, well-crystallized W-doped VO2 with
      low phase transition temperature, excellent solar heat shielding ability and
      considerable anti-oxidation ability was synthesized by a solid-state reaction
      process. The phase transition temperature was reduced from 67.3  degrees C to
      10.8  degrees C at 2.0% W doping with an efficiency of -28.1  degrees C per at%.
      Importantly, an excellent balance between the phase transition temperature and
      the latent heat was obtained at high doping levels (1.5-2.0%). Furthermore, W
      doped VO2 particles exhibited a significantly longer exposure time (more than 5
      h) at 300  degrees C in air than the previously reported 2 h in the literature,
      and the corresponding derived composite foils showed excellent luminous
      transmittance and solar heat shielding properties (Tlum = 49.9% and Tsol = 44.8%
      for 2.0% W doping).

PMID- 27711688
TI  - The influences of operating conditions and design configurations on the
      performance of symmetric electrochemical capacitors.
AB  - The influence of different charging current densities, charging times and several
      structural designs on symmetric electrochemical capacitor (EC) performance,
      including capacitance, energy density and power density, has been investigated
      via modelling and simulation. Understanding the effects of different operating
      conditions and structural design variables on a capacitor's performance will
      guide in the optimal design and fabrication of high performance ECs. The
      operating conditions and design configurations examined were charging current
      density, charging times, electrode and electrolyte effective conductivity,
      electrode thickness and electrode porosity. The results reveal that ECs with low
      electrode and electrolyte effective conductivities can only be effectively
      charged at low current density for long times. ECs with a high concentration of
      impurity ions or redox species exhibit high self-discharge rates, and fast
      charging of the ECs greatly reduces the self-discharge rate, compared to slow
      charging, provided that the effective conductivities of the electrode and
      electrolyte are high enough. The simulation showed the typical electrode length
      scale over which the liquid potential drop occurs and electrode utilization can
      be employed as a design parameter to optimize electrode thickness (effective
      thickness) for ECs designed to operate under a specific current density range.
      The expression for electrode utilization (u) and the guidelines that can also be
      used to determine optimum electrode thickness/effective thickness (100% electrode
      utilization), optimum charging time and optimum current density in a cell of a
      given voltage and effective conductivity of electrode and electrolyte, were
      derived. The energy and power density of ECs were increased when the electrode
      thickness was reduced in the given charging conditions. The Ragone plots can be
      used to select optimum electrode dimensions to attain given energy and power
      density specifications.

PMID- 27711689
TI  - An efficient and inexpensive water-oxidizing manganese-based oxide electrode.
AB  - Using inexpensive and environmentally friendly Mn oxide, a very simple method to
      synthesize an efficient and stable water-oxidizing electrode on the surface of a
      fluorine doped tin oxide electrode was reported. The electrode at pH = 13 yields
      a current density of 1 mA cm-2 at an overpotential of 450 mV, which is promising
      to be used as an anode in water-splitting systems. In higher overpotential (800
      mV), a current density of 7 mA cm-2 was observed. Proposed different states of
      the growth of layered Mn oxide on the surface of FTO based on SEM images were
      also discussed.

PMID- 27711690
TI  - Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by
      using lanthanide-doped upconversion nanoparticles.
AB  - Platinum-based chemotherapy, although it has been well proven to be effective in
      the battle against cancer, suffers from limited specificity, severe side effects
      and drug resistance. The development of new alternatives with potent anticancer
      effects and improved specificity is therefore urgently needed. Recently, there
      are some new chemotherapy reagents based on photoactive Re(i) complexes which
      have been reported as promising alternatives to improve specificity mainly
      attributed to the spatial and temporal activation process by light irradiation.
      However, most of them respond to short-wavelength light (e.g. UV, blue or green
      light), which may cause unwanted photo damage to cells. Herein, we demonstrate a
      system for near-infrared (NIR) light controlled activation of Re(i) complex
      cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide
      doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the
      Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs
      and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed
      effective inactivation of both drug susceptible human ovarian carcinoma A2780
      cells and cisplatin resistant subline A2780cis cells by our UCNP based system
      with NIR irradiation, and there was minimum light toxicity observed in the whole
      process, suggesting that such a system could provide a promising strategy to
      control localized activation of Re(i) complexes and therefore minimize potential
      side effects.

PMID- 27711691
TI  - HONH3Cl optimized CH3NH3PbI3 films for improving performance of planar
      heterojunction perovskite solar cells via a one-step route.
AB  - Planar heterojunction perovskite solar cells (PHJ-PSCs) constructed with one-step
      precursor solution spin-coating deposition (OPSSD) usually give an extremely low
      performance mainly due to the poor morphology and low crystallinity of the
      perovskite films. In this work, by incorporating a suitable HONH3Cl additive in
      the perovskite precursor solution, a high quality perovskite film with improved
      morphology and crystallinity was obtained. The UV-vis measurement of the CH3NH3I
      solutions without and with HONH3Cl demonstrates that the improved quality of the
      perovskite film can be easily attributed to a combined effect of N2, I2, H2O and
      CH3NH3Cl originating from the oxidation of CH3NH3I triggered by the HONH3Cl
      additive, which can manipulate the crystallization process of the perovskite.
      Accordingly, the improved performance for the HONH3Cl-induced PHJ-PSCs can also
      be demonstrated. At the optimized molar ratio of 1 : 1 : 0.1 for PbI2 : CH3NH3I :
      HONH3Cl, the PHJ-PSCs exhibit an average power conversion efficiency (PCE) of
      10.61 +/- 0.51%, which is much higher than that of pristine 1 : 1 : 0 based cells
      without additive (7.21 +/- 0.61%), and the best performing HONH3Cl-induced device
      can yield a PCE as high as 11.12% with a Jsc of 18.42 mA cm-2, Voc of 0.95 V and
      FF of 0.63. Introducing suitable HONH3Cl as an additive into the perovskite
      precursor solution is really an effective route to enhance the performance of the
      PHJ-PSCs via OPSSD.

PMID- 27711692
TI  - Synthesis of a highly efficient 3D graphene-CNT-MnO2-PANI nanocomposite as a
      binder free electrode material for supercapacitors.
AB  - Graphene based nanocomposites have been investigated intensively, as electrode
      materials for energy storage applications. In the current work, a graphene-CNT
      MnO2-PANI (GCM@PANI) nanocomposite has been synthesized on 3D graphene grown on
      nickel foam, as a highly efficient binder free electrode material for
      supercapacitors. Interestingly, the specific capacitance of the synthesized
      electrode increases up to the first 1500 charge-discharge cycles, and is thus
      referred to as an electrode activation process. The activated GCM@PANI
      nanocomposite electrode exhibits an extraordinary galvanostatic specific
      capacitance of 3037 F g-1 at a current density of 8 A g-1. The synthesized
      nanocomposite exhibits an excellent cyclic stability with a capacitance retention
      of 83% over 12 000 charge-discharge cycles, and a high rate capability by
      retaining a specific capacitance of 84.6% at a current density of 20 A g-1. The
      structural and electrochemical analysis of the synthesized nanocomposite suggests
      that the astonishing electrochemical performance might be attributed to the
      growth of a novel PANI nanoparticle layer and the synergistic effect of CNT/MnO2
      nanostructures.

PMID- 27711693
TI  - Room temperature magnetoelectric coupling in intrinsic multiferroic Aurivillius
      phase textured ceramics.
AB  - Spark plasma sintering was employed in order to obtain textured Aurivillius phase
      ceramics that simultaneously exhibit ferroelectric and ferromagnetic properties
      at room temperature. The sintered multiferroics are layer-structured, nearly
      single-phase materials. Although a small amount of the secondary phase consisting
      of magnetic Co and Fe was detected by SEM/EDX, a majority of the observed
      ferromagnetic behaviour was attributed to the Aurivillius phase
      Bi4.25La0.75Ti3Fe0.5Co0.5O15 based on the observed magnetic anisotropy. The
      ferroelectric switching was demonstrated to exist in the Aurivillius phase
      ceramics by measuring the current peaks upon electric field reversal.
      Piezoresponse force microscopy at room temperature revelaed substantial changes
      of the ferroelectric domain structure when the Aurivillius phase material is
      subjected to an external magnetic field.

PMID- 27711694
TI  - Control of calcium accessibility over hydroxyapatite by post-precipitation steps:
      influence on the catalytic reactivity toward alcohols.
AB  - Hydroxyapatites are increasingly used as heterogeneous catalysts since they
      present atypical behaviours for many acid base reactions. The aim of this study
      was to discuss the possible involvement of Ca2+ Lewis and/or PO-H Bronsted acid
      sites belonging to the hydroxyapatite system in the conversion of 2-methylbut-3
      yn-1-ol, a model molecule that is known to account for the acid base properties,
      and of ethanol into n-butanol. A series of hydroxyapatite samples with similar
      bulk properties was prepared from a lone precipitation batch, but by varying the
      conditions of the washing and drying steps. Although the surface depth probed by
      XPS exhibited similar average composition, ISS analysis revealed a gradient of
      calcium concentration in the first surface layers. In fact, the different
      conditions of drying and washing resulted in a modulation of the relative amount
      of Ca2+ and PO-H accessible on the top surface, as revealed by the adsorption of
      the CO molecule monitored by FTIR. The conversion in the two alcohol molecules is
      linearly dependent on the nature of the acid base pairs involved: when accessible
      on the top surfaces, due to their stronger acidity, the Ca2+ Lewis acid sites are
      preferentially involved, but they are less efficient than PO-H, as illustrated by
      the linear decrease of the conversion levels with the increasing relative amount
      of accessible Ca2+ cations. It is thus concluded that PO-H sites enhance the
      performances of the catalysts for the two reactions, and that washing and drying
      conditions allowing us to decrease the calcium accessibility at the benefit of PO
      H should be favoured.

PMID- 27711695
TI  - Ultrafast relaxation dynamics of electronically excited piperidine: ionization
      signatures of Rydberg/valence evolution.
AB  - We have investigated the electronic relaxation dynamics of gas-phase piperidine
      (a secondary aliphatic amine) using time-resolved photoelectron imaging.
      Following 200 nm excitation, spectrally sharp and highly anisotropic
      photoelectron data reveal ultrafast (60 fs) internal conversion between the
      initially excited 3px Rydberg state and the lower-lying 3s Rydberg state,
      mediated by the evolution of nsigma* valence character along the 3px N-C bond.
      This behaviour is in good agreement with previously reported findings for several
      tertiary aliphatic amines. In contrast to the these systems, however, much
      broader photoelectron signals exhibiting only very small angular anisotropy and
      two distinct decay timescales (180 fs and 1.7 ps) were also observed. As
      confirmed by our supporting calculations, this is attributable to nsigma* valence
      character now evolving along the N-H stretching coordinate within the 3s Rydberg
      state as the molecule starts dissociating to yield H atom photoproducts in
      conjunction with ground state piperidinyl radicals. By analogy with systems such
      as ammonia and morpholine, we conclude this event may occur either promptly or,
      alternatively, via a "frustrated" process where the system repeatedly traverses
      the upper cone of a conical intersection with the ground state until the required
      region of phase space is sampled to facilitate non-adiabatic population transfer.
      Our findings reveal the role of several different nuclear coordinate motions in
      driving stepwise internal conversion across multiple potential energy surfaces
      and the distinct photoionization signatures that are associated with these
      processes.

PMID- 27711696
TI  - Attachment of composite porous supra-particles to air-water and oil-water
      interfaces: theory and experiment.
AB  - We developed and tested a theoretical model for the attachment of fluid-infused
      porous supra-particles to a fluid-liquid interface. We considered the wetting
      behaviour of agglomerated clusters of particles, typical of powdered materials
      dispersed in a liquid, as well as of the adsorption of liquid-infused
      colloidosomes at the liquid-fluid interface. The free energy of attachment of a
      composite spherical porous supra-particle made from much smaller aggregated
      spherical particles to the oil-water interface was calculated. Two cases were
      considered: (i) a water-filled porous supra-particle adsorbed at the oil-water
      interface from the water phase, and, (ii) an oil-filled porous supra-particle
      adsorbed at the oil-water interface from the oil-phase. We derived equations
      relating the three-phase contact angle of the smaller "building block" particles
      and the contact angle of the liquid-infused porous supra-particles. The theory
      predicts that the porous supra-particle contact angle attached at the liquid
      interface strongly depends on the type of fluid infused in the particle pores and
      the fluid phase from which it approaches the liquid interface. We tested the
      theory by using millimetre-sized porous supra-particles fabricated by evaporation
      of droplets of polystyrene latex suspension on a pre-heated super-hydrophobic
      surface, followed by thermal annealing at the glass transition temperature. Such
      porous particles were initially infused with water or oil and approached to the
      oil-water interface from the infusing phase. The experiment showed that when
      attaching at the hexadecane-water interface, the porous supra-particles behaved
      as hydrophilic when they were pre-filled with water and hydrophobic when they
      were pre-filled with hexadecane. The results agree with the theoretically
      predicted contact angles for the porous composite supra-particles based on the
      values of the contact angles of their building block latex particles measured
      with the Gel Trapping Technique. The experimental data for the attachment of
      porous supra particles to the air-water interface from both air and water also
      agree with the theoretical model. This study gives important insights about how
      porous particles and particle aggregates attach to the oil-water interface in
      Pickering emulsions and the air-water surface in particle-stabilised aqueous
      foams relevant in ore flotation and a range of cosmetic, pharmaceutical, food,
      home and personal care formulations.

PMID- 27711697
TI  - Smart Inorganic Polymers.

PMID- 27711698
TI  - Ambiguous electrocatalytic CO2 reduction behaviour of a nickel
      bis(aldimino)pyridine pincer complex.
AB  - The electrochemical properties of two Ni(NNN)X2 pincer complexes are reported
      where X = Cl or Br and NNN is N,N'-(2,6-diisopropylphenyl)bis-aldiminopyridine.
      Cyclic voltammetry under 1 atm of CO2 suggests electrocatalytic CO2 reduction
      activity, however, bulk electrolysis shows a poor Faradaic efficiency for CO
      evolution with a high Faradaic yield for H2 evolution.

PMID- 27711699
TI  - Facile synthesis of hierarchical Mn3O4 superstructures and efficient catalytic
      performance.
AB  - The development of novel materials with excellent performance depends not only on
      the constituents but also on their remarkable micro/nanostructures. In this work,
      manganese oxide (Mn3O4) hausmannite structures with a uniform three-dimensional
      (3D) flower-like hierarchical architecture have been successfully synthesized by
      a novel chemical route using surfactants as structure-directing agents.
      Microstructure analysis indicates that the obtained 3D flower-like Mn3O4
      superstructure consists of a large number of two-dimensional (2D) Mn3O4
      nanosheets, which is different from the reported 3D Mn3O4 hierarchical structures
      based on zero-dimensional nanoparticles or one-dimensional nanowires and
      nanorods. This 3D Mn3O4 hierarchical architecture provides us with another type
      of manganese oxide with different superstructural characteristics, which may have
      potential practical applications in the catalytic degradation of organic
      pollutants. The catalytic performance of this hierarchical Mn3O4 superstructure,
      which was prepared by three different types of structure-directing agents,
      including cetyltrimethylammonium bromide (CTAB), poly(vinylpyrrolidone) (PVP),
      and poly(ethylene oxide)-poly(propylene oxide) (P123), was evaluated for the
      catalytic degradation of organic pollutants, e.g. methylene blue. Interestingly,
      the hierarchical Mn3O4 superstructure prepared using CTAB as a template showed
      efficient catalytic degradation. The formation processes and possible growth
      mechanism of this novel 3D Mn3O4 hierarchical superstructure assembled by 2D
      Mn3O4 nanosheets are discussed in detail.

PMID- 27711700
TI  - Insight into the mechanism about the initiation, growth and termination of the C
      C chain in syngas conversion on the Co(0001) surface: a theoretical study.
AB  - The initiation, growth and termination mechanism of the C-C chain from syngas on
      the Co(0001) surface have been investigated using DFT calculations. Our results
      show that CHx (x = 1-3) formation is easier than CH3OH, both CH and CH2 species
      are the dominant forms of CHx (x = 1-3), both CH and CH2 species dominantly
      interact with CHO to form CHCHO and CH2CHO, and realizes the initial C-C chain
      formation. Then, CHCHO and CH2CHO prefer to be successively hydrogenated to
      CH3CHO, followed by C-O bond cleavage to give CH3CH; subsequently, CHO insertion
      into CH3CH can realize the further chain growth to form CH3CHCHO, followed by
      dissociation and hydrogenation to give CH3CHCH and CH3CH2CHO, respectively;
      further, CH3CHCH hydrogenation or CH3CH2CHO dissociation via the C-O bond
      cleavage can form the CH3CH-like species CH3CH2CH intermediate. Thus, the
      mechanism of a C-C chain growth cycle has been proposed that starts from a
      CH3CH2CH intermediate, followed by repeating the above C-C chain growth cycle via
      CH3CH intermediates, and the C-C chain growth to higher C2+ hydrocarbons and
      oxygenates can be realized, in which RCH2CH prefers to interact with CHO to form
      RCH2CHCHO, followed by its C-O bond cleavage and its hydrogenation to form R'CHCH
      (R' = RCH2) and R'CH2CHO (R' = RCH2), respectively, where R'CHCH hydrogenation
      and C-O bond cleavage of R'CH2CHO will produce R'CH2CH. Moreover, aldehyde
      intermediates R'CH2CHO are expected to undergo C-O bond cleavage to five R'CH2CH
      (R' = RCH2) rather than its desorption and its hydrogenation to alcohol. The C-C
      chain termination occurs at three possible positions along the growth cycle:
      R'CH2CHO desorption, R'CHCH with successive hydrogenation steps to alkanes or
      alkenes, and R'CH2CH hydrogenation to alkanes, in which the relative importance
      of termination of R'CHCH and R'CH2CH with hydrocarbons will depend strongly on
      the hydrogen coverage on the metal surface. The results of this work not only
      illustrate the initiation, growth and termination mechanism of the C-C chain
      involved in FTS on the Co(0001) surface, but also serve as a basis for the
      rational design of other Co surfaces toward desirable higher hydrocarbons or
      oxygenates.

PMID- 27711701
TI  - Impact electrochemistry on screen-printed electrodes for the detection of
      monodispersed silver nanoparticles of sizes 10-107 nm.
AB  - Impact electrochemistry provides a useful alternative technique for the detection
      of silver nanoparticles in solutions. The combined use of impact electrochemistry
      on screen-printed electrodes (SPEs) for the successful detection of silver
      nanoparticles provides an avenue for future on-site, point-of-care detection
      devices to be made for environmental, medicinal and biological uses. Here we
      discuss the use of screen-printed electrodes for the detection of well-defined
      monodispersed silver nanoparticles of sizes 10, 20, 40, 80, and 107 nm.

PMID- 27711703
TI  - Quantum molecular motion in the mixed ion-radical complex, [(H2O)(H2S)].
AB  - The cation dimer of water and hydrogen sulfide, [(H2O)(H2S)]+, serves as a
      fundamental model for the oxidation chemistry of H2S. The known oxidative
      metabolism of H2S by biological species in sulfur-rich environments has motivated
      the study of the inherent properties of this benchmark complex, with possible
      mechanistic implications for modern water oxidation chemistry. The low-energy
      isomer of this open-shell ion is a proton-transferred (PT) structure, H3O+SH. An
      alternative PT structure, H3S+OH, and a hemibonded (HB) isomer, [H2O.SH2]+, are
      also stable isomers, placing this complex intermediate to known (H2O)2+ (PT) and
      (H2S)2+ (HB) limiting regimes. This intermediate character suggested the
      possibility of unique molecular motion, even in the vibrational ground state.
      Path integral molecular dynamics and anharmonic vibrational spectroscopy
      simulations have been performed in this study, in order to understand the
      inherent quantum molecular motion of this complex. The resulting structural
      distributions were found to deviate significantly from both classical and
      harmonic analyses, including the observation of large-amplitude anharmonic motion
      of the central proton and nearly free rotation of the terminal hydrogens. The
      predicted vibrational spectra are particularly unique and suggest characteristic
      signatures of the strong electronic interactions and anharmonic vibrational mode
      couplings in this radical cation.

PMID- 27711702
TI  - Fluorescent zinc(ii) complexes for gene delivery and simultaneous monitoring of
      protein expression.
AB  - Two new zinc(ii) complexes, [Zn(l-His)(NIP)]+(1) and [Zn(acac)2(NIP)](2) (where
      NIP is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline, acac = acetyl
      acetone), have been synthesized and characterized by elemental analysis, UV-vis,
      fluorescence, IR, 1H NMR and electron spray ionization mass spectroscopies. Gel
      retardation assay, atomic force microscopy and dynamic light scattering studies
      show that 1 and 2 can induce the condensation of circular plasmid pBR322 DNA into
      nanometer size particles under ambient conditions. Treatment of 2 with 5 mM EDTA
      restored 30% of the supercoiled form of DNA, revealing partial reversibility of
      DNA condensation. The in vitro transfection experiment demonstrates that the
      complexes can be used to deliver pCMV-tdTomato-N1 plasmid which expresses red
      fluorescent protein. The confocal studies show that the fluorescent nature of
      complexes is advantageous for visualizing the intracellular delivery of metal
      complexes as well as transfection efficiency using two distinct emission windows.

PMID- 27711704
TI  - Phthalocyanine based molecular spintronic devices.
AB  - Molecular spintronics is an effervescent field of research, which aims at
      combining spin physics and molecular nano-objects. In this article, we show that
      phthalocyanine molecules integrated in magnetic tunnel junctions (MTJs) can lead
      to magnetoresistance effects of different origins. We have investigated cobalt
      and manganese phthalocyanine molecule based magnetic tunnel junctions. CoPc MTJs
      exhibit both tunneling magnetoresistance (TMR) and tunneling anisotropic
      magnetoresistance (TAMR) effects of similar magnitude. However, for MnPc MTJs, a
      giant TAMR dominates with ratios up to ten thousands of percent. Strong features
      visible in the conductance suggest that spin-flip inelastic electron tunneling
      processes occur through the Mn atomic chain formed by the MnPc stacks. These
      results show that metallo-organic molecules could be used as a template to
      connect magnetic atomic chains or even a single magnetic atom in a solid-state
      device.

PMID- 27711705
TI  - Liquid silver tris(perfluoroethyl)trifluorophosphate salts as new media for
      propene/propane separation.
AB  - A series of silver tris(perfluoroethyl)trifluorophosphate (Ag[FAP]) complexes
      with various ligands (acetonitrile ACN, chloroacetonitrile Cl-ACN, acrylonitrile
      acryl-CN, pyridine py, ethylenediamine en and propene C3H6) have been synthesized
      starting from Ag[NO3] and K[FAP] using three different routes. Physicochemical
      properties as well as crystal structures ([Ag(ACN)2/4][FAP], [Ag(py)2][FAP]) were
      determined and the suitability of such Ag salts for propene/propane separation
      processes was investigated. The investigated silver complexes exhibit either low
      melting points or form liquid complexes when contacted with gaseous propene at 30
      degrees C. This makes them promising separation materials for both liquid
      membranes and absorber fluids due to their high silver content and significant
      propene capacity. Single (iGSC) and mixed (NMR) gas solubilities as well as
      diffusion coefficients (PFG-NMR) of propene and propane were determined to
      predict the theoretical selectivity of solubility, membrane selectivity, capacity
      and transport properties of the silver salts according to the solution diffusion
      model. A strong influence of the number and type of ligands on chemical
      complexation, physicochemical properties and separation performance has been
      observed.

PMID- 27711706
TI  - Radiative cooling of H3O+ and its deuterated isotopologues.
AB  - In conjunction with ab initio potential energy and dipole moment surfaces for the
      electronic ground state, we have made a theoretical study of the radiative
      lifetimes for the hydronium ion H3O+ and its deuterated isotopologues. We compute
      the ro-vibrational energy levels and their associated wavefunctions together with
      Einstein coefficients for electric dipole transitions. A detailed analysis of the
      stability of the ro-vibrational states has been carried out and the longest
      living states of the hydronium ions have been identified. We report estimated
      radiative lifetimes and cooling functions for temperatures <200 K. A number of
      long-living meta-stable states are identified, capable of population trapping.

PMID- 27711707
TI  - Prediction of proton affinities of organic molecules using the any-particle
      molecular-orbital second-order proton propagator approach.
AB  - We assess the performance of the recently developed any-particle molecular
      orbital second-order proton propagator (APMO/PP2) scheme [M. Diaz-Tinoco, J.
      Romero, J. V. Ortiz, A. Reyes and R. Flores-Moreno, J. Chem. Phys., 2013, 138,
      194108] on the calculation of gas phase proton affinities (PAs) of a set of 150
      organic molecules comprising several functional groups: amines, alcohols,
      aldehydes, amides, ketones, esters, ethers, carboxylic acids and carboxylate
      anions. APMO/PP2 PAs display an overall mean absolute error of 0.68 kcal mol-1
      with respect to experimental data. These results suggest that the APMO/PP2 method
      is an alternative approach for the quantitative prediction of gas phase proton
      affinities. One novel feature of the method is that a PA can be obtained from a
      single calculation of the optimized protonated molecule.

PMID- 27711708
TI  - Coordination versatility of p-hydroquinone-functionalized dibenzobarrelene-based
      PC(sp3)P pincer ligands.
AB  - The manuscript describes the synthesis and coordination chemistry of a novel
      diphosphine pincer ligand based on a p-hydroquinone-functionalized
      dibenzobarrelene scaffold. The p-hydroquinone fragment of the ligand is
      oxidatively and coordinatively non-innocent and may render new reactivity to the
      metal center due to implied reversible redox behavior, tautomeric interconversion
      and metal-hydroxyl/alkoxide coordination switch of the pendant hydroxyl side-arm.
      Palladium, platinum and iridium complexes were prepared and characterized.
      Investigation of their coordination chemistry revealed that while tautomeric
      equilibrium exists in free ligands and in the chelate non-metalated complexes, it
      is essentially blocked in the corresponding C(sp3)-pincer compounds due to
      stabilizing hemilabile coordination of the hydroxyl group. However, its presence
      in close proximity to the metal center is essential for catalyzing acceptorless
      dehydrogenation of alcohols by the iridium complexes via the outer-sphere
      hydrogen transfer mechanism. Remarkably, we found a similar activity for the
      analogous palladium complexes, which is not characteristic of this metal. This
      unprecedented reactivity of palladium stresses the fact that besides the choice
      of an active metal, transformation-oriented design of the ligand is crucial for
      catalysis.

PMID- 27711709
TI  - A scalable architecture for quantum computation with molecular nanomagnets.
AB  - A proposal for a magnetic quantum processor that consists of individual molecular
      spins coupled to superconducting coplanar resonators and transmission lines is
      carefully examined. We derive a simple magnetic quantum electrodynamics
      Hamiltonian to describe the underlying physics. It is shown that these hybrid
      devices can perform arbitrary operations on each spin qubit and induce tunable
      interactions between any pair of them. The combination of these two operations
      ensures that the processor can perform universal quantum computations. The
      feasibility of this proposal is critically discussed using the results of
      realistic calculations, based on parameters of existing devices and molecular
      qubits. These results show that the proposal is feasible, provided that molecules
      with sufficiently long coherence times can be developed and accurately integrated
      into specific areas of the device. This architecture has an enormous potential
      for scaling up quantum computation thanks to the microscopic nature of the
      individual constituents, the molecules, and the possibility of using their
      internal spin degrees of freedom.

PMID- 27711710
TI  - Surface functionalized H2Ti3O7 nanowires engineered for visible-light
      photoswitching, electrochemical water splitting, and photocatalysis.
AB  - This article demonstrates comprehensive studies on different visible-light driven
      photoelectrochemical and photocatalytic aspects of a hydrothermally synthesized n
      type H2Ti3O7 (HTO) nanowire mesh and its carbon and nitrogen functionalized
      counterparts, namely C-HTO and N-HTO. It was found that the presence of various
      defect states within the band gap of HTO, C-HTO and N-HTO nanowires, make them
      photoactive under visible-light. The photo-conversion efficiencies of HTO, C-HTO,
      and N-HTO nanowire electrodes are about 0.066, 0.129, and 0.076%, respectively,
      at around 1 V vs. Ag/AgCl. Carbon functionalization of HTO nanowires has been
      found to be most beneficial in increasing the charge carrier density, resulting
      in the highest current density, high photo conversion efficiency, remarkable
      photoelectrochemical water splitting performance and enhanced photocatalytic
      activity. The photocurrent density of the C-HTO NWs was found to be 0.0562 mA cm
      2 at 1 V vs. Ag/AgCl, which is almost two times that of the pristine HTO NWs
      (0.029 mA cm-2). Although nitrogen functionalization increases the charge carrier
      density of the HTO nanowires, nitrogen incorporation produces lots of
      recombination centres in the nanowires, which are found to play a detrimental
      role in the photoelectrochemical and photocatalytic performance of N-HTO
      nanowires, limiting the expected performance. Therefore, the present study
      demonstrates a suitable surface engineering technique for nanostructures to
      maximize the utilization of green solar light.

PMID- 27711711
TI  - Highly effective ion-pair receptors based on 2,2-bis(aminomethyl)-propionic acid.
AB  - Compounds 2 and 3 were designed and prepared as heteroditopic ion-pair receptors.
      The design features a 2,2-bis(aminomethyl)propionic acid core to connect and pre
      organize binding groups. The cation binding is provided by a sodium selective N
      acyl aza-18-crown-6 subunit whereas for anion complexation, two urea groups
      (receptor 2) or two squaramide groups (receptor 3) were introduced. Beyond acting
      as anion binding sites, the urea and squaramide groups were used to support
      sodium cation complexation through metal carbonyl oxygen lone pair interactions.
      The receptors were found to bind sodium salts of chloride, bromide and nitrate
      much more strongly than the corresponding ions accompanied by counterions that do
      not coordinate to the receptor. For example, chloride binding to receptor 2
      enhances the strength of sodium complexation by up to 23 times. Conversely,
      sodium binding enhances chloride recognition by a factor of three. Receptor 3
      containing squaramide units, binds sodium chloride and bromide with a similar
      albeit lower cooperativity. Moreover, unprecedentedly tight binding of these
      salts was achieved, with association constants as high as log Ka = 6.52 M-1 for
      NaCl salt complexation.

PMID- 27711712
TI  - Atomically precise understanding of nanofluids: nanodiamonds and carbon nanotubes
      in ionic liquids.
AB  - A nanofluid (NF) is composed of a base liquid and suspended nanoparticles (NPs).
      High-performance NFs exhibit significantly better heat conductivities, as
      compared to their base liquids. In the present work, we applied all-atom
      molecular dynamics (MD) simulations to characterize diffusive and ballistic
      energy transfer mechanisms within nanodiamonds (NDs), carbon nanotubes (CNTs),
      and N-butylpyridinium tetrafluoroborate ionic liquid (IL). We showed that heat
      transfer within both NDs and CNTs is orders of magnitude faster than that in the
      surrounding IL, whereas diffusion of all particles in the considered NF is
      similar. Intramolecular heat transfer in NPs is a key factor determining the
      difference of NFs from base liquids. Solvation free energy of NDs and CNTs in ILs
      was estimated from MD simulations. The geometric dimensions of NPs were shown to
      be a major source of entropic penalty. Temperature adjusts the entropic factor
      substantially by modifying a genuine local structure of the bulk base liquid. Our
      work contributes to engineering more stable and productive suspensions of NPs in
      ILs, which are necessary for essential progress in the field of NFs.

PMID- 27711713
TI  - Insight into the reactivity of in situ formed {(NbO2)3SiW9}: synthesis,
      structure, and solution properties of a trimeric polytungstosilicate trapping a
      {MnNb9} core.
AB  - A new trimeric cluster [(SiW9Nb3O38)3MnO3(H2O)3]13- (1) with three Keggin-type
      trilacunary SiW9 units connected by a {MnNb9} core were structurally
      characterized. The polyanion 1 features three corner-shared {Nb3O3} fragments
      that are linked to each other on two sides via three Nb-O-Nb bridges and by a
      {MnII} linker. To the best of our knowledge, polyanion 1 represents the first
      example of a trimeric niobotungstate cluster reported to date, and is revealed
      for the first time uniting a family of polytungstosilicate clusters. The
      formation of polyanion 1 exemplifies the reactivity of {(NbO2)3SiW9} with a
      manganese metal ion, defining a new in situ synthetic strategy for {(NbO2)3SiW9}
      based derivatives, featuring POM chemistry between Nb/W mixed-addendum POMs and
      various transition-metal or lanthanide species.

PMID- 27711714
TI  - Reaction mechanisms of carbon dioxide, ethylene oxide and amines catalyzed by
      ionic liquids BmimBr and BmimOAc: a DFT study.
AB  - The mechanisms of the one-pot conversion of carbon dioxide, ethylene oxide, and
      aniline to 3-phenyl-2-oxazolidionone catalyzed by the binary ionic liquids of
      BmimBr and BmimOAc were explored using the DFT methods. The complex reaction
      above comprises of two parallel reactions and a subsequent cascade reaction. DFT
      calculations on reaction pathways and energy profiles reveal that the
      electrostatic and hydrogen-bond effects of BmimBr play a crucial role in the
      parallel reactions for the generation of ethylene carbonate and 2-phenylamino
      ethanol. Further, the subsequent cascade reaction to generate 3-phenyl-2
      oxazolidinone catalyzed by BmimOAc follows a stepwise mechanism, which is more
      favorable than the concerted mechanism governed by BmimBr. In addition, BmimBr
      can accelerate the side reaction of aniline and ethylene oxide to yield a mixture
      of oligomers, which accords with the experimental observation. This theoretical
      work provides a deep insight into the catalytic roles of binary ionic liquids and
      also inspires us to design high efficient catalysts for the conversion of carbon
      dioxide further.

PMID- 27711715
TI  - Maximizing ion current rectification in a bipolar conical nanopore fluidic diode
      using optimum junction location.
AB  - The ion current rectification has been obtained as a function of the location of
      a heterojunction in a bipolar conical nanopore fluidic diode for different
      parameters to determine the junction location for maximum ion current
      rectification using numerical simulations. Forward current peaks for a specific
      location of the junction and reverse current decreases with the junction location
      due to a change in ion enrichment/depletion in the pore. The optimum location of
      the heterojunction shifts towards the tip with base/tip diameter and surface
      charge density, and towards the base with the electrolyte concentration. The
      optimum location of the heterojunction has been approximated by an equation as a
      function of pore length, base/tip diameter, surface charge density and
      electrolyte concentration. The study is useful to design a rectifier with maximum
      ion current rectification for practical purposes.

PMID- 27711716
TI  - Iron-catalyzed clean dehydrogenative coupling of alcohols with P(O)-H compounds:
      a new protocol for ROH phosphorylation.
AB  - An efficient oxygen-phosphoryl bond-forming reaction via iron-catalyzed cross
      dehydrogenative coupling has been developed. This transformation proceeds
      efficiently under oxidant- and halide-free reaction conditions with H2
      liberation, and represents a straightforward method to prepare valuable
      organophosphoryl compounds from the readily available alcohols and P(O)-H
      compounds.

PMID- 27711717
TI  - Transition metal complexes of the pyridylphosphine ligand o-C6H4(CH2PPy2)2.
AB  - The synthesis and coordination behaviour of the pyridylphosphine ligand o
      C6H4(CH2PPy2)2 (Py = 2-pyridyl) are reported. The phosphine selenide was
      synthesised and the 1JPSe value of 738 Hz indicates the phosphorus atoms have a
      similar basicity to PPh3. The ligand reacts with platinum(ii) and palladium(ii)
      complexes to give simple diphosphine complexes of the type [MX2(PP)] (M = Pt, X =
      Cl, I, Me, Et; M = Pd, X = Cl, Me). When the ligand is reacted with
      chloromethyl(hexa-1,5-diene)platinum the [PtClMe(PP)] complex results, from which
      a series of unsymmetrical platinum complexes of the type [PtMeL(PP)]+ (L = PPh3,
      PTA, SEt2 and pyridine) can be made. This enabled the comparison of the cis and
      trans influences of a range of ligands. The following cis influence series was
      compiled based on 31P NMR data of these complexes: Py ~ Cl > SEt2 > PTA > PPh3.
      Reaction of [PtClMe(PP)] with NaCH(SO2CF3)2 and carbon monoxide slowly formed an
      acyl complex, where the CO had inserted in the Pt-Me bond. Attempts to achieve
      P,P,N chelation, through abstracting the chloride ligand in [PtClMe(PP)], were
      unsuccessful. When the ligand reacted with platinum(0), palladium(0) and
      silver(i) complexes the bis-chelated complexes [M(PP)2] (M = Pt, Pd) and
      [Ag(PP)2]+ were formed respectively. Reaction of the ligand with [Ir(COD)(MU
      Cl)]2 formed [IrCl(PP)(COD)]. When the chloride ligand was abstracted, the
      pyridyl nitrogens were able to interact with the iridium centre facilitating the
      isomerisation of the 1,2,5,6-eta4-COD ligand to a 1-kappa-4,5,6-eta3-C8H12
      ligand. The X-ray crystal structure of [Ir(1-kappa-4,5,6-eta3-C8H12)(PPN)]BPh4
      confirmed the P,P,N chelation mode of the ligand. In solution, this complex
      displayed hemilabile behaviour, with the pyridyl nitrogens exchanging at a rate
      faster than the NMR time scale at room temperature.

PMID- 27711718
TI  - Water bridges anchored by a C-HO hydrogen bond: the role of weak interactions in
      molecular solvation.
AB  - The imidazole group, characterized by an activated C(2)-H bond sandwiched between
      two N atoms, occurs in several biomolecules including alkaloids, amino acids, and
      nucleobases. The speculated role of this potential hydrogen bond donor in shaping
      the solvation shell around the neutral imidazole moiety, however, remains
      unidentified. In contrast, hydrogen bonding and electrostatic interactions are
      commonly observed in the imidazolium cation where the acidity of the C(2)-H bond
      is markedly enhanced. Here, we show direct evidence of the weakly activated C(2)
      H bond in shaping the solvation shell of neutral imidazole, via spectroscopic
      characterization of the water clusters (Wn, n = 2-4) of two model compounds,
      benzimidazole (BIM) and N-methylbenzimidazole (MBIM). Infrared spectra in the OH,
      NH, and CH stretching regions allow unambiguous detection of a N-WW-C(2)H binding
      motif in the doubly hydrated cluster of both molecules. Remarkably, H-bonded
      water bridges between the N atom and N-H bond in BIM-W3,4 clusters are switched
      to the C(2)-H bond in MBIM-W3,4 with comparable binding strength, indicating that
      the weakly activated C(2)-H bond in the neutral imidazole moiety can serve as a
      potent H-bond donor.

PMID- 27711719
TI  - Poly(n-alkylsilsesquioxane) liquids prepared by cosolvent-free hydrolytic
      polycondensation of n-alkyltrialkoxysilanes: effects of liquid-liquid phase
      separation during aging and alkyl chain length on structure and viscosity.
AB  - The effect of the alkyl chain length and alkoxy groups on the viscosity and
      related properties of polysilsesquioxanes (PSQs) prepared by cosolvent-free
      hydrolytic polycondensation from n-alkyltrialkoxysilane-water binary systems via
      aging was investigated. n-Alkyltrialkoxysilanes with ethyl, n-propyl, and n-butyl
      groups gave PSQ liquids, whereas those with methyl groups yielded gels. The
      viscosity of the PSQ liquids remained stable over a month at room temperature
      despite the presence of many SiOH groups, and decreased with an increase in the
      alkyl chain length. The aging step was crucial for obtaining PSQ liquids with low
      viscosities, and both n-alkyltrimethoxysilane and n-alkyltriethoxysilane with the
      same alkyl group produced PSQ liquids with comparable viscosities. However,
      during aging, liquid-liquid phase separation occurred only in the solutions
      derived from alkyltrimethoxysilanes. These observations confirmed that liquid
      liquid phase separation is not essential for the preparation of PSQ liquids. The
      temperature dependence of the viscosity indicated that the PSQ liquids are
      fragile.

PMID- 27711720
TI  - Fabrication of RGD-conjugated Gd(OH)3:Eu nanorods with enhancement of magnetic
      resonance, luminescence imaging and in vivo tumor targeting.
AB  - The development of multimodal probes with magnetic resonance imaging (MRI) and
      intraoperative fluorescence imaging is the most challenging task in the field of
      tumor diagnosis. Herein, a simple one-pot hydrothermal method is used to prepare
      Eu-doped Gd(OH)3 nanorods (Gd(OH)3:Eu NRs) with good fluorescence and the
      longitudinal relaxivity r1 value of 4.78 (Gd mM s-1). After dual-functionalized
      maleimide-polyethylene glycol-succinimide (Mal-PEG-NHS) macromolecules are coated
      on the surface of Gd(OH)3:Eu NRs (PEG-NRs), the results of a lower degradation
      ratio in newborn calf serum (NCS), reactive oxygen species (ROS) generation in
      L929 cells and the hemolytic rate of PEG-NRs show their good cyto-compatibility
      and longer blood circulation time. Moreover, the actively tumor-targeting
      properties are endowed to NRs through the conjugation of cyclic arginine-glycine
      aspartic acid (cRGD) (denoted RGD-NRs). The bio-distributions of RGD-NRs in tumor
      bearing nude mice via tail-vein injection indicate that RGD-NRs are specifically
      taken-up by gliomas. The tests of in vivo T1-weighted MR imaging via tail-vein
      injection confirm that RGD-NRs possess a higher positive signal-enhancement
      ability in gliomas. Besides, the better luminescence imaging of living cells
      under a fluorescence microscope and the clear in vivo fluorescence imaging
      further confirm the targeting properties and better in vivo optical imaging
      behavior of RGD-NRs.

PMID- 27711721
TI  - Unraveling the sub-nanoscopic structure at interphase in a poly(vinyl alcohol)
      MOF nanocomposite, and its role in thermo-mechanical properties.
AB  - A microscopic model of the interfacial region is required to improve
      understanding of the role of local structure in bulk physical properties in metal
      organic framework-based polymer nanocomposites. A zeolitic imidazolate framework
      (ZIF-8)-based (loading 2-30 wt%) composite of poly vinyl alcohol (PVA) is studied
      as a model system to investigate the role of interfacial interaction in molecular
      packing, glass transition process and tensile properties. Attractive interfacial
      interaction between the surface of ZIF particles and PVA chains is established by
      Fourier transform infra red (FTIR) measurements. The morphology of the
      nanocomposites is characterized using X-ray diffraction and scanning electron
      microscopy (SEM), showing that aggregation of particles started from 5 wt% of ZIF
      8. At low loadings, occurrence of two glass transitions measured using
      differential scanning calorimetry indicates two spatial zones, viz. interphase
      and bulk layers, of different packing density in the PVA matrix. With increase in
      loading, molecular packing throughout the polymer matrix is changed as the
      interparticle distance and interphase width become comparable. At the highest
      loading, PVA shows bulk glass transition temperature because of the non
      significant volume fraction of interphase resulting from aggregation of ZIF.
      Molecular packing (free volume structure) of PVA in the nanocomposites is
      investigated using ortho-positronium lifetime distributions, which show that
      large vacant spaces are created at the interfacial region leading to a low
      density interphase. The existence of a low-density interphase is also supported
      by bulk-density measurements of the nanocomposites. Tensile testing measurements
      show a decrease in ductility of the nanocomposites, indicating enhancement in
      rigidity of polymer chains at the interfacial region because of attractive
      interfacial interaction. This study indicates that the polymer chain framework at
      the interfacial region in PVA-MOF nanocomposites can be represented by a rigid
      but rather open network.

PMID- 27711722
TI  - Hydrazine as a hydrogen carrier in the photocatalytic generation of H2 using CdS
      quantum dots.
AB  - The compelling need for safe storage and transportation of H2 has made liquid
      phase materials safer H2-carriers with a high gravimetric and volumetric hydrogen
      density. Unlike thermal or electrocatalytic decomposition on precious metal
      catalysts, a photocatalytic route to decomposing these liquid-phase materials can
      offer triggered onboard production of H2 and help mitigate the safety issues
      concerned with H2 storage. We have investigated visible-light induced H2
      evolution from aqueous hydrazine using CdS quantum dots (QDs) as metal-free
      photocatalysts. Hydrazine acts as a H2 carrier as well as a donor, giving rise to
      a visible-light induced H2 evolution activity as high as 33 mmol h-1 g-1 at pH 8.
      This has been achieved by the use of CdS QDs capped with S2- ligands. The use of
      larger ligands such as mercaptopropionic acid hinders the adsorption of hydrazine
      onto CdS QDs and significantly decreases the activity. The effect of pH on the
      hydrogen yield in aqueous hydrazine has also been examined.

PMID- 27711724
TI  - Switching between porphyrin, porphodimethene and porphyrinogen using cyanide and
      fluoride ions mimicking volatile molecular memory and the 'NOR' logic gate.
AB  - beta-Functionalization of meso-tetrakis(3,5-di-tert-butyl-4
      hydroxyphenyl)porphyrin with electron acceptors such as formyl and dicyanovinyl
      has been reported for the first time. 2-Formyl-5,10,15,20-tetrakis(3',5'-di-tert
      butyl-4'-hydroxyphenyl)porphyrinatocopper(ii) (Cu-TDtBHPP-CHO) crystallizes in
      the triclinic space group P1[combining macron], [a = 10.8479(4) A, b = 14.6207(5)
      A, c = 15.9745(5) A, V = 2198.97(13) A3] and exhibits an almost planar structure
      and a square planar geometry. beta-Formyl/dicyanovinyl substituted porphyrins
      such as Cu-TDtBHPP-CHO, Ni-TDtBHPP-CHO, Cu-TDtBHPP-MN (1), Ni-TDtBHPP-MN (2) and
      H2-TDtBHPP-MN (3) exhibited red-shifted optical absorption features
      (Deltalambdamax = 13-40 nm) in CH2Cl2 compared to the corresponding MTPPs. beta
      Dicyanovinyl substituted porphyrins were developed as a quantitatively operating
      'lab-on-a-molecule' for the visual detection of F- and CN- ions. Having a CN- ion
      responsive dicyanovinyl moiety and a F- ion responsive redox-active 3,5-di-tert
      butyl-4-hydroxyphenyl groups, they detect F- and CN- ions simultaneously by
      switching unique structural changes between porphyrin, porphodimethene and
      porphyrinogen along with distinct colour changes which were monitored by UV-Vis
      NIR, fluorescence and NMR spectroscopic techniques.

PMID- 27711723
TI  - Water inhibits CO oxidation on gold cations in the gas phase. Structures and
      binding energies of the sequential addition of CO, H2O, O2, and N2 onto Au.
AB  - We report a detailed experimental and theoretical study of the gas phase
      reactivity of Au+ with CO, O2, N2 and their mixtures in the presence of a trace
      amount of water impurity. The gold cation is found to strongly interact with CO
      and H2O molecules via successive addition reactions until reaching saturation.
      The stoichiometry of the formed complex is determined by the strength of the
      binding energy of the neutral molecule to the gold cation. CO binds the strongest
      to Au+, followed by H2O, N2 and then O2. We found that the gold cation (Au+) can
      activate the O2 molecule within the Au+(CO)2(O2) complex which could react with
      another CO molecule to form Au+(CO)(CO2) + CO2. The product Au+(CO)(CO2) is
      observed experimentally with a small intensity at room temperature. However, the
      presence of water leads to the formation of Au+(CO)(H2O)(O2) instead of
      Au+(CO)2(O2) due to the strong interaction between Au+ and water. The current
      experiments and calculations might lead to a molecular level understanding of the
      interactions between the active sites, reactants and impurities which could pave
      the way for the design of efficient nanocatalysts.

PMID- 27711725
TI  - Sulphur-rich functionalized calix[4]arenes for selective complexation of Hg2+
      over Cu2+, Zn2+ and Cd2.
AB  - The syntheses of two new ligands based on a calix[4]arene scaffold in the cone
      conformation functionalized on the phenolic positions 1 and 3 by
      diethylthiophosphonates (L1) or tetra(tri)thioethyleneglycol (L2) crowns are
      described. Together with ligand L3, the parent calix[4]arene substituted by a
      penta(tetra)thioethyleneglycol crown, the spectroscopic properties of the ligands
      were determined by means of UV-Vis absorption spectroscopy and steady-state and
      time-resolved fluorescence spectroscopy, showing that the ligands display modest
      but non-negligible intrinsic fluorescence properties (phifluo = 0.023; 0.026 and
      0.029 for L1, L2 and L3 in CH2Cl2, respectively). The X-ray crystal structures of
      ligand L1, and of its synthetic precursor were determined and analyzed for their
      capacity to accommodate the incoming cationic species. The ligands were further
      investigated for their complexation properties of divalent cations such as Cu2+,
      Zn2+, Hg2+ and Cd2+ (under their nitrate salts) in 1 : 1 CH3CN/CH2Cl2 solutions
      (I = 0.01 M Et4NNO3, T = 25.0(2)  degrees C), in which the additions of cations
      were monitored by absorption and steady-state fluorescence spectrophotometries.
      The stoichiometries of the corresponding complexes were assessed by ESI-MS, while
      insights into the structures of the complexes in solution were obtained with
      density functional theory (DFT) calculations. The influence of the sulphur and
      phenol coordinating moieties was addressed to show that the thiocrown compounds
      L2 and L3 displayed a marked affinity towards the soft mercuric cation (Deltalog
      K >= 2), with no particular size selectivity effect, whereas ligand L1 can
      accommodate both the thio and phenol units to coordinate with Cu(ii). Altogether,
      these results point to the use of L3 as a selective fluoroionophore for detection
      of Hg2+.

PMID- 27711726
TI  - Highly stable selenadiazole derivatives induce bladder cancer cell apoptosis and
      inhibit cell migration and invasion through the activation of ROS-mediated
      signaling pathways.
AB  - Bladder cancer is still a common malignancy of the urinary tract due to the high
      metastasis rate and unexpected side effects of drug treatments. The acidic
      environment of the urinary bladder also strongly limits the efficacy of the
      chemotherapeutic agents during the treatment of bladder cancer. In this study, a
      series of selenadiazole derivatives (SeDs) have been rationally designed and
      synthesized and could actively suppress the progression and metastasis of bladder
      cancer cells. SeDs demonstrated better antiproliferative activity and higher
      stability under different physiological conditions, especially in an acidic
      urocystic environment, than mitomycin, a clinically used anti-bladder cancer
      drug. In particular, compound 1b displayed better selectivity between cancer and
      normal cells in comparison with other compounds. Studies on the structure
      activity relationship revealed that the introduction of strong electron donating
      substituents, such as the methoxy group, resulted in a dramatic enhancement in
      the anticancer efficacy. Furthermore, 1b induced anti-migration and anti-invasion
      activities against bladder cancer cells. Mechanistic investigation revealed that
      compound 1b was able to enter the cells through endocytosis and then trigger
      reactive oxygen species (ROS) overproduction, further causing DNA damage-mediated
      p53 phosphorylation and promoting cancer cell apoptosis by regulating the AKT and
      MAPKs signaling pathways. Altogether, the study provides a strategy for rational
      design of selenadiazole derivatives with improved stability to antagonize bladder
      cancer.

PMID- 27711727
TI  - A ligand substituted tungsten iodide cluster: luminescence vs. singlet oxygen
      production.
AB  - Octahedral tungsten iodide clusters equipped with apical ligands (L) are
      synthesized to implement substantial photophysical properties. The
      [W6I8(CF3COO)6]2- cluster reported herein is the first example of a family of
      ligand substituted [W6I8L6]2- clusters. Such compounds are expected to exhibit a
      rich photochemistry in which the apical ligands play a crucial role. The
      versatile solid state and solution phase photophysical properties of
      (TBA)2[W6I8(CF3COO)6] described herein parallel characteristics obtained in some
      photophysically active organic compounds, including a broad absorption in the
      UV/VIS region. Upon irradiation of this compound, a broad red emission is
      observed in the VIS/NIR region resulting from excited triplet states, and singlet
      oxygen (a1Deltag) is generated in the presence of O2.

PMID- 27711728
TI  - ZnGeSb2: a promising thermoelectric material with tunable ultra-high
      conductivity.
AB  - First principles calculations predict the promising thermoelectric material
      ZnGeSb2 with a huge power factor (S2sigma/tau) on the order of 3 * 1017 W m-1 K-2
      s-1, due to the ultra-high electrical conductivity scaled by a relaxation time of
      around 8.5 * 1025 Omega-1 m-1 s-1, observed in its massive Dirac state. The
      observed electrical conductivity is higher than the well-established Dirac
      materials, and is almost carrier concentration independent with similar behaviour
      of both n and p type carriers, which may certainly attract device applications.
      The low range of thermal conductivity is also evident from the phonon dispersion.
      Our present study further reports the gradual phase change of ZnGeSb2 from a
      normal semiconducting state, through massive Dirac states, to a topological semi
      metal. The maximum power factor is observed in the massive Dirac states compared
      to the other two states.

PMID- 27711729
TI  - Singlet oxygen generation properties of isometrically dibromated thienyl
      containing aza-BODIPYs.
AB  - Isometrically dibromated thienyl-containing aza-BODIPYs CDB-1 and BDB-2 with
      potential use as photosensitizers (PSs) were successfully prepared and their
      photophysical properties were fully characterized. Singlet oxygen generation
      experiments were also performed. In this regard, PS CDB-1 was found to be more
      effective and had about two-fold rate enhancement compared to PS BDB-2. DFT and
      TD-DFT calculations helped to provide insights into the distinct intersystem
      crossing (ISC) processes observed for CDB-1 and BDB-2.

PMID- 27711730
TI  - Lanthanide contraction for helicity fine-tuning and helix-winding control of
      single-helical metal complexes.
AB  - Lanthanide contraction was used for helicity fine-tuning and helix winding
      control of single-helical tetranuclear complexes LZn3Ln (Ln = La-Lu); heavier
      lanthanides formed a tighter helix with a higher M/P ratio and gave a more
      abundant partially-coiled structure, resulting in 14-step structural control of
      the helical complexes.

PMID- 27711731
TI  - Peripheral halo-functionalization in [Cu(N^N)(P^P)]+ emitters: influence on the
      performances of light-emitting electrochemical cells.
AB  - A series of heteroleptic [Cu(N^N)(P^P)][PF6] complexes is described in which P^P
      = bis(2-(diphenylphosphino)phenyl)ether (POP) or 4,5-bis(diphenylphosphino)-9,9
      dimethylxanthene (xantphos) and N^N = 4,4'-diphenyl-6,6'-dimethyl-2,2'-bipyridine
      substituted in the 4-position of the phenyl groups with atom X (N^N = 1 has X =
      F, 2 has X = Cl, 3 has X = Br, 4 has X = I; the benchmark N^N ligand with X = H
      is 5). These complexes have been characterized by multinuclear NMR spectroscopy,
      mass spectrometry, elemental analyses and cyclic voltammetry; representative
      single crystal structures are also reported. The solution absorption spectra are
      characterized by high energy bands (arising from ligand-centred transitions)
      which are red-shifted on going from X = H to X = I, and a broad metal-to-ligand
      charge transfer band with lambdamax in the range 387-395 nm. The ten complexes
      are yellow emitters in solution and yellow or yellow-orange emitters in the solid
      state. For a given N^N ligand, the solution photoluminescence (PL) spectra show
      no significant change on going from [Cu(N^N)(POP)]+ to [Cu(N^N)(xantphos)]+;
      introducing the iodo-functionality into the N^N domain leads to a red-shift in
      lambda compared to the complexes with the benchmark N^N ligand 5. In the solid
      state, [Cu(1)(POP)][PF6] and [Cu(1)(xantphos)][PF6] (fluoro-substituent) exhibit
      the highest PL quantum yields (74 and 25%, respectively) with values of tau1/2 =
      11.1 and 5.8 MUs, respectively. Light-emitting electrochemical cells (LECs) with
      [Cu(N^N)(P^P)][PF6] complexes in the emissive layer have been tested. Using a
      block-wave pulsed current driving mode, the best performing device employed
      [Cu(1)(xantphos)]+ and this showed a maximum luminance (Lummax) of 129 cd m-2 and
      a device lifetime (t1/2) of 54 h; however, the turn-on time (time to reach
      Lummax) was 4.1 h. Trends in performance data reveal that the introduction of
      fluoro-groups is beneficial, but that the incorporation of heavier halo
      substituents leads to poor devices, probably due to a detrimental effect on
      charge transport; LECs with the iodo-functionalized N^N ligand 4 failed to show
      any electroluminescence after 50 h.

PMID- 27711732
TI  - Effect of dopant concentration on visible light driven photocatalytic activity of
      Sn1-xAgxS2.
AB  - Tin(iv) sulfide (SnS2), as a mid-band-gap semiconductor shows good potential as
      an excellent photocatalyst due to its low cost, wide light spectrum response and
      environment-friendly nature. However, to meet the demands of large-scale water
      treatment, a SnS2 photocatalyst with a red-shifted band gap, increased surface
      area and accelerated molecule and ion diffusion is required. Doping is a facile
      method to manipulate the optical and chemical properties of semiconductor
      materials simultaneously. In this work, SnS2 photocatalysts with varied Ag doping
      content are synthesized through a facile one-step hydrothermal method. The
      product is characterized by XRD, SEM, TEM and UV-Vis spectrometry. The
      photocatalytic activity of the as-prepared Sn1-xAgxS2 is studied by the
      degradation of methylene blue (MB) dye under solar light irradiation. It is found
      that increasing the Ag dopant concentration can effectively increase the solar
      light adsorption efficiency of the photocatalyst and accelerate heterogeneous
      photocatalysis. The optimal concentration of Ag dopant is found to be 5% with the
      highest rate constant being 1.8251 hour-1. This study demonstrates that an
      optimal amount of Ag doping can effectively increase the photocatalytic
      performance of SnS2 and will promote the commercialization of such photocatalysts
      in the photocatalytic degradation of organic compounds.

PMID- 27711733
TI  - Manganese clusters of aromatic oximes: synthesis, structure and magnetic
      properties.
AB  - With the aim of tuning the structures by using oxime ligands with different non
      coordinating groups, three aromatic oxime ligands were designed by fusing oxime
      groups ([double bond, length as m-dash]N-OH) onto different non-coordinating
      groups. Their reactions with the corresponding Mn(ii) salts gave five manganese
      clusters [Mn(MU3-O)(L1)3(DMF)(H2O)3Cl].2DMF.CH3OH (1), [Mn(MU3
      O)(L2)3(OAc)(CH3OH)2] (2), [Mn(MU3-O)2(L2)6(H2O)(py)7](ClO4)2.py.0.5CH3OH.2H2O
      (3), [MnO4(L2)8(DMF)4].DMF.6CH3CN (4), and [MnMnO4(L3)12].3DMF.6H2O (5), in which
      H2L1, H2L2 and HL3 represent indane-1,2,3-trione-1,2-dioxime, acenaphthenequinone
      dioxime, and 9,10-phenanthrenedione-9-oxime, respectively. Their structures were
      determined and studied in detail. 1 and 2 show planar triangular trinuclear Mn
      structures. 3 has a hexanuclear Mn skeleton formed from two Mn triangular units
      through inter-trinuclear mutual coordination. 4 and 5 present octanuclear
      skeletons constructed from planar triangular Mn3O and tetrahedral Mn4O secondary
      building units, respectively, with different symmetries and different oxidation
      states of the manganese ions. Their structural studies reveal a significant
      contribution of the parent rings for fusing oxime groups, different non
      coordinating groups and anions to the formation of different cluster skeletons.
      Their magnetic properties were investigated and simulated, which revealed the
      presence of dominant antiferromagnetic interactions between the metal ions in
      these compounds.

PMID- 27711734
TI  - Unprecedentedly enhanced solar photocatalytic activity of a layered titanate
      simply integrated with TiO2 nanoparticles.
AB  - We report a simple, low-cost methodology for unprecedentedly enhancing the
      photocatalytic activity of layered inorganic semiconductors. A layered titanate
      with a lepidocrocite-type structure scarcely showed photocatalytic activity for a
      test reaction, the oxidative decomposition of formic acid in water into CO2,
      under simulated solar light, but it showed highly enhanced photocatalytic
      activity upon mixing with a much smaller amount (approximately 10 wt%) of
      commercially available TiO2 nanoparticles (P25) in water. The photocatalytic
      activity of the mixture was approximately 5 times that of P25, a benchmark
      photocatalyst. From various analyses, the enhancement resulted from the transfer
      of photoexcited electrons from the layered titanate to P25 at their particle
      interfaces and retardation of charge recombination. When applied to a
      photocatalyst for H2 production from water containing methanol under simulated
      solar light, the layered titanate/P25 mixture showed considerably enhanced
      activity and the apparent quantum yield was 23% (at 320 nm). By replacing P25
      with Pt co-catalyst-loaded P25, the apparent quantum yield of the mixture
      increased from 23 to 73%, although an extremely small amount (below 0.06%) of Pt
      was used in the system.

PMID- 27711736
TI  - The coordination of amidoxime ligands with uranyl in the gas phase: a mass
      spectrometry and DFT study.
AB  - Sequestering uranium from the ocean is a promising solution to fulfill the demand
      for nuclear energy. Motivated by this purpose, a series of amidoxime ligands and
      their analogs have been developed with high absorption capacity and selectivity.
      An in-depth understanding of the structural information of the uranyl-ligand
      complexes is essential to improve the performance of the ligands. Herein, we have
      studied the coordination of three amidoxime ligands (6-methoxyl-naphtha-2
      amidoxime, NAO; glutarimidedioxime, GIO; and gluardiamidoxime, GDO) with uranyl
      in the gas phase by mass spectrometry. The identifications of the electrospray
      ionization (ESI) generated species, the fragmentation pathways upon dissociation,
      the relative binding affinities of the ligands, and the hydration reactions have
      been conducted and compared to reveal their structural information in the gas
      phase. The binding modes for all the complexes were suggested based on the
      experimental results and were further studied by density functional theory (DFT)
      calculations.

PMID- 27711735
TI  - A nanostructured hematite film prepared by a facile "top down" method for
      application in photoelectrochemistry.
AB  - To overcome tough conditions currently used for the preparation of nanostructured
      hematite films on a conducting substrate, a rational and easy method of chemical
      etching involving Fe3+ release and material growth in the presence of OH- has
      been developed. By carefully tuning the parameters influencing the morphologies
      of hematite, including the synthetic procedure, the concentration of etching
      solution, temperature, etching time and the morphology controlling surfactant,
      hematite films grown on iron foil with various morphologies (e.g. nanorod,
      nanowire, ultrathin nanoflake and cauliflower-like shape) have been achieved. In
      particular, it is found that F- is an effective surfactant to control the
      morphology as well as the crystallization process of hematite. Ultrathin
      nanoflakes having a minimized feature size exhibit the best photocurrent of 0.5
      mA cm-2 (1.23 V vs. RHE, RHE is reversible hydrogen electrode) among the samples
      tested as a result of facilitated hole diffusion to the electrolyte and thus
      lowered carrier recombination. Compared with pristine hematite, a nearly tripled
      photocurrent is observed when H2O2 is added in the electrolyte as a hole
      scavenger, suggesting the presence of a charge injection barrier in the surface
      of samples. According to this, the strategy of Co2+ treatment is utilized and the
      improved photocurrent is seen, likely due to the improved water oxidation
      kinetics and surface state passivation. We believe that this convenient and
      economical method can be extended to the synthesis of other alkaline metal oxide
      nanomaterials as long as the redox potential of S2O82-/SO42- is higher than Mn+/M
      (M refers to metal).

PMID- 27711737
TI  - Gas phase RDX decomposition pathways using coupled cluster theory.
AB  - Electronic and free energy barriers for a series of gas-phase RDX decomposition
      mechanisms have been obtain using coupled cluster singles, doubles, and
      perturbative triples with complete basis set (CCSD(T)/CBS) electronic energies
      for MBPT(2)/cc-pVTZ structures. Importantly, we have located a well-defined
      transition state for NN homolysis, in the initial RDX decomposition step, thereby
      obtaining a true barrier for this reaction. These calculations support the view
      that HONO elimination is preferred at STP over other proposed mechanisms,
      including NN homolysis, "triple whammy" and NONO isomerization. Indeed, our
      calculated values of Arrhenius parameters are in agreement with experimental
      findings for gas phase RDX decomposition. We also investigate a number of new
      pathways leading to breakdown of the intermediate formed by the initial HONO
      elimination, and find that NN homolysis in this intermediate has an activation
      energy barrier comparable with that computed for HONO elimination.

PMID- 27711738
TI  - How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a
      proof-of-concept study.
AB  - The role of Cu and Zn ions in Alzheimer's disease is linked to the consequences
      of their coordination to the amyloid-beta (Abeta) peptide, i.e. to the modulation
      of Abeta aggregation and to the production of Reactive Oxygen Species (ROS), two
      central events of the so-called amyloid cascade. The role of both ions in Abeta
      aggregation is still controversial. Conversely the higher toxicity of the redox
      competent Cu ions (compared to the redox inert Zn ions) in ROS production is
      acknowledged. Thus the Cu ions can be considered as the main therapeutic target.
      Because Zn ions are present in higher quantity than Cu ions in the synaptic
      cleft, they can prevent detoxification of Cu by chelators unless they have an
      unusually high Cu over Zn selectivity. We describe a proof-of-concept study where
      the role of Zn on the metal swap reaction between two prototypical ligands and
      the Cu(Abeta) species has been investigated by several complementary
      spectroscopic techniques (UV-Vis, EPR and XANES). The first ligand has a higher
      Cu over Zn selectivity relative to the one of Abeta peptide while the second one
      exhibits a classical Cu over Zn selectivity. How Zn impacts the effect of the
      ligands on Cu-induced ROS production and Abeta aggregation is also reported.

PMID- 27711741
TI  - Excited-state dynamics of the medicinal pigment curcumin in a hydrogel.
AB  - Curcumin is a yellow polyphenol with multiple medicinal effects. These effects,
      however, are limited due to its poor aqueous stability and solubility. A hydrogel
      of 3% octadecyl randomly substituted polyacrylate (PAAC18) has been shown to
      provide high aqueous stability for curcumin under physiological conditions,
      offering a route for photodynamic therapy. In this study, the excited-state
      photophysics of curcumin in the PAAC18 hydrogel is investigated using a
      combination of femtosecond transient absorption and fluorescence upconversion
      spectroscopy. The transient absorption results reveal a multiexponential decay in
      the excited-state kinetics with fast (1 ps & 15 ps) and slow (110 ps & ~5 ns)
      components. The fast decay component exhibits a deuterium isotope effect with D2O
      in the hydrogel, indicating that the 15 ps decay component is attributable to
      excited-state intramolecular hydrogen atom transfer of curcumin in the PAAC18
      hydrogel. In addition, solvent reorganisation of excited-state curcumin is
      investigated using multiwavelength femtosecond fluorescence upconversion
      spectroscopy. The results show that the dominant solvation response (tau = 0.08
      ps) is a fast inertial motion owing to the presence of bulk-like water in the
      vicinity of the hydrophobic octadecyl substituents of the PAAC18 hydrogel. The
      results also show an additional response with longer time constants of 1 and 6
      ps, which is attributable to translational diffusion of confined water molecules
      in the three-dimensional, cross-linking network of the octadecyl substituents of
      PAAC18. Overall, we show that excited-state intramolecular hydrogen atom transfer
      and solvent reorganisation are major photophysical events for curcumin in the
      PAAC18 hydrogel.

PMID- 27711739
TI  - First quadruple-glycine bridging mono-lanthanide-substituted borotungstate
      hybrids.
AB  - A class of novel organic-inorganic hybrid lanthanide (Ln)-substituted Keggin-type
      borotungstates K4Na4H4[Ln2(gly)4(alpha-BW11O39)2].23H2O [Ln = Ce3+ (1), Pr3+ (2),
      Nd3+ (3), Sm3+ (4), Eu3+ (5), Tm3+ (6); gly = glycine] have been synthesized from
      the reaction of K8[BW11O39H].13H2O, NaAc.6H2O and Ln(NO3)3.6H2O by employing gly
      ligands as structure-stabilizing agents in the conventional aqueous solution
      system and structurally characterized by elemental analyses, IR spectroscopy,
      thermogravimetric (TG) analyses, powder X-ray diffraction (PXRD) and single
      crystal X-ray diffraction. The common prominent structural feature of isomorphic
      1-6 is that all of them consist of two mono-Ln-substituted Keggin [Ln(alpha
      BW11O39)]6- fragments linked by four gly ligands, furnishing an intriguing
      dimeric assembly of the quadruple-gly-connective mono-Ln-substituted
      borotungstate, in which each carboxylic oxygen atom from gly ligands is bound to
      Ln3+ cations in the MU2-O or MU3-O mode. To the best of our knowledge, 1-6
      represent the first examples of inorganic-organic hybrid Ln-substituted
      borotungstates functionalized by quadruple amino acid bridges. The solid-state
      photoluminescence properties of 3-5 have been determined at ambient temperature
      and the photoluminescence emission spectra exhibit the characteristic emission
      bands derived from Ln3+ centers. The thermostability of 1-6 has been studied and
      the thermal decomposition procedure of 3 has been comprehensively investigated
      with the assistance of variable-temperature PXRD patterns and variable
      temperature IR spectra. Furthermore, magnetic susceptibility measurements of 1, 2
      and 4 have been conducted.

PMID- 27711740
TI  - Reactivity of cyclopentadienyl transition metal(ii) complexes with borate
      ligands: structural characterization of the toluene-activated molybdenum complex
      [Cp*Mo(CO)2(eta3-CH2C6H5)].
AB  - Reactions of cyclopentadienyl transition-metal halide complexes [Cp*Mo(CO)3Cl],
      1, and [CpFe(CO)2I], 2, (Cp = C5H5; Cp* = eta5-C5Me5) with borate ligands are
      reported. Treatment of 1 with [NaBt2] (Bt2 = dihydrobis(2-mercapto
      benzothiazolyl)borate) in toluene yielded [Cp*Mo(CO)2(C7H4S2N)], 3, and
      [Cp*Mo(CO)2(eta3-CH2C6H5)], 4, with a selective binding of toluene through C-H
      activation followed by orthometallation. Note that compound 4 is a structurally
      characterized toluene-activated molecule in which the metal is in eta3
      coordination mode. Under similar reaction conditions, [NaPy2] (Py2 = dihydrobis(2
      mercaptopyridyl)borate) produced only the mercaptopyridyl molybdenum complex
      [Cp*Mo(CO)2(C5H4SN)], 5, in good yield. On the other hand, when compound 2 was
      treated individually with [NaBt] (Bt = trihydro(2-mercapto-benzothiazolyl)borate)
      and [NaPy2] in THF, formation of the eta1-coordinated complexes
      [CpFe(CO)2(C7H4S2N)], 6, and [CpFe(CO)2(C5H4SN)], 7, was observed. The solid
      state molecular structures of compounds 3, 4, 6, and 7 have been established by
      single-crystal X-ray crystallographic analyses.

PMID- 27711742
TI  - Constructing B and N separately co-doped carbon nanocapsules-wrapped Fe/Fe3C for
      oxygen reduction reaction with high current density.
AB  - The exploration of low-cost and highly efficient non-platinum electrocatalysts
      for the oxygen reduction reaction (ORR) is vital for renewable systems. Herein,
      we report a novel non-platinum electrocatalyst consisting of B and N separately
      co-doped graphitic carbon encapsulated Fe/Fe3C nanoparticles (BNGFe), which were
      synthesized from a facile method by adopting melamine, iron nitrate and boric
      acid as the precursors. In this synthesis, the N atoms in melamine first bond
      with the iron ions in iron nitrate, which could prevent the formation of BN
      covalent bonds during the subsequent pyrolysed process, resulting in the
      formation of effective B and N separately co-doped graphitic carbon encapsulated
      on the Fe/Fe3C nanoparticles. The synthetic BNGFe catalyst shows outstanding
      catalytic performance for ORR with an onset potential of 0.98 V (vs. RHE) and a
      high limiting diffusion current density, which could be comparable to the state
      of-the-art commercial Pt/C catalyst in alkaline electrolyte.

PMID- 27711743
TI  - Overview of the crystal chemistry of the actinide chalcogenides: incorporation of
      the alkaline-earth elements.
AB  - This review focuses on the results of exploratory syntheses of alkaline-earth
      metal actinide chalcogenides Ak-An-Q (Ak = Ba, Sr; An = Th, U; Q = S, Se, and
      Te). About thirty new compounds are described. Although the basic building blocks
      of their structures are usually AnQ6 octahedra and AkQ8 bicapped trigonal prisms,
      these are combined in diverse ways to afford eleven new structure types. The
      structures reconfirm the prevailing presence of An4+ in chalcogenides, although
      some of the compounds discovered are mixed An4+/An5+ systems, and a few contain
      only An5+. The tendency of the chalcogens to form Q-Q bonds is again evident from
      the presence of S-S single bonds and infinite Te-Te-Te linear chains. The latter
      possess interatomic distances of lengths greater than that of a Te-Te single bond
      but less than that of a Te-Te van der Waals interaction. Assignment of formal
      oxidation states in compounds containing these chains is arbitrary at best.
      Addition of metal atoms (M) affords quaternary structures, some of which show
      remarkable flexibility in the positions of the An and M atoms, and in such
      compounds the nature of the M elements influences directly the dimensionality of
      the resultant structure. The presence of adventitious oxygen, often from etching
      of the fused-silica tubes by oxyphilic An elements, results in new quintary
      compounds that show remarkable structural variations with change of M. The
      compounds discussed have shown transport and electronic structures that range
      from metallic-like to semiconducting. We find, with the exception of BaUSe3, when
      comparisons can be made that the values of the calculated band gaps are
      reasonably close but usually lower than the experimentally derived values. Thus
      the method used, in particular the HSE functional, has been generally successful
      on these 5f actinides. This is an important result because in the absence of
      suitable crystals, and hence experimental measurements, it still may be possible
      to offer credible predictions of some of the magnetic and electronic properties
      of the compounds.

PMID- 27711744
TI  - Niobium tetrachloride complexes with thio-, seleno- and telluro-ether
      coordination - synthesis and structures.
AB  - NbCl4 reacts with the dithioethers MeS(CH2)nSMe (n = 2 or 3), iPrS(CH2)2SiPr or o
      C6H4(CH2SEt)2 in a 1 : 1 molar ratio in CH2Cl2 or toluene over several days, to
      give red or orange, paramagnetic complexes, [NbCl4(dithioether)]. Their X-ray
      crystal structures confirm distorted octahedral geometries with chelating
      dithioether. MeS(CH2)2SMe, alone, also forms an [NbCl4{MeS(CH2)2SMe}2] complex
      based upon eight-coordinate Nb(iv) in a square antiprismatic geometry. Similar
      six-coordinate cis-[NbCl4(diselenoether)] are formed by MeSe(CH2)nSeMe (n = 2 or
      3) and nBuSe(CH2)3SenBu. The monodentate ligands Me2S, Me2Se and nBu2Se form
      [NbCl4(R2E)2] (E = S, Se) which are unstable in solution, losing R2E to form
      complexes with a 1 : 1 stoichiometry, which are shown to be diamagnetic dimers,
      [(Me2E)Cl3Nb(MU-Cl)2NbCl3(Me2E)], with single Nb-Nb sigma-bonds. Tellurium
      ligands tend to decompose in these reactions, but reaction at room temperature of
      Me2Te and NbCl4 formed [NbCl4(Me2Te)2], the X-ray structure of which revealed an
      eight-coordinate dimer, [Nb2Cl4(MU-Cl)4(Me2Te)4]. The new complexes have been
      characterised by microanalysis, IR, UV-visible spectroscopy and magnetic
      measurements. X-ray crystal structures are reported for [NbCl4(L-L)] (L-L =
      MeS(CH2)nSMe, n = 2 or 3, iPrS(CH2)2SiPr, o-C6H4(CH2SEt)2, MeSe(CH2)3SeMe),
      [Nb2Cl8(Me2Te)4], [Nb2Cl8(Me2S)2] and [Nb2Cl8(Me2Se)2]. The complexes are very
      sensitive to moisture and dioxygen, and some also readily undergo C-E bond
      cleavage. Two ligand fragmentation products were identified -[Nb2Cl4(MU
      S)2{MeS(CH2)3SMe}2] and [Nb2Cl4(MU-Se)2{o-C6H4(CH2)2Se}4]. X-ray crystal
      structures are also reported for the oxidation/hydrolysis products [NbOCl3(Me2S)]
      and [NbOCl3{MeS(CH2)2SMe}].

PMID- 27711745
TI  - Four new 3D metal-organic frameworks constructed by the asymmetrical
      pentacarboxylate: gas sorption behaviour and magnetic properties.
AB  - By using an asymmetrical rigid pentacarboxylic acid ligand, 2,4-di(3',5'
      dicarboxylphenyl)benzoic acid (H5L), four new three-dimensional (3D) metal
      organic frameworks (MOFs), namely {[Cu2(HL)(H2O)2].2DMF.2H2O}n (1),
      {[Co2(L)(DMA)].H2N(Me)2}n (2), {[Co2(L)(H2O)].H2N(Me)2}n (3),
      {[Mn2(L)(DMF)(H2O)].H2N(Me)2}n (4), were solvothermally synthesized. H5L in 1-4
      shows different coordination modes and can easily form various metal clusters
      (secondary building units, SBUs) in the final structures. 1 is a 3D porous
      framework with a (4,4)-connected pts topology based on the [Cu2(COO)4]
      paddlewheel SBU, wherein six SBUs are connected by twelve HL4- to get an
      unprecedented Cu12 hendecahedron nanocage. 2-4 possess similar dinuclear
      [M2(COO)5] SBUs (M = Co, Mn), which are further extended by L5- to give rise to
      3D frameworks with the uncommon (5,5)-connected nia-5,5-P21/c and bnn topologies.
      In addition, the desolvated framework of 1 contains polar channels decorated with
      uncoordinated carboxylate groups, leading to selective adsorption for CO2 over
      CH4 at 195, 273 and 298 K. Moreover, the magnetic properties of 1-4 show that
      there exist antiferromagnetic interactions between metal ions.

PMID- 27711746
TI  - Highly sensitive and selective fluorescent probes for Hg2+ in Ag(i)/Cu(ii) 3D
      supramolecular architectures based on noncovalent interactions.
AB  - Three novel metal-organic assemblies (MOAs), namely, [Ag(2,4'-Hpdc)(4,4'-bpy)]n
      (1), [Ag(2,2'-Hpdc)(4,4'-bpy)0.5]n (2), and [Cu(2,2'-Hpdc)2(1,4-bib)]n (3) [2,4'
      H2pdc = 2,4'-biphenyldicarboxylic acid; 2,2'-H2pdc = 2,2'-biphenyldicarboxylic
      acid; 4,4'-bpy = 4,4'-bipyridine; 1,4-bib = 1,4-bis(1-imidazolyl)benzene] have
      been hydrothermally synthesized by using mixed ligands and characterized by
      single crystal X-ray diffraction, infrared (IR), elemental analysis and
      thermogravimetric analysis (TGA). The crystal structures of the three compounds
      indicate that the hydrogen bonding (C-HO and C-Hpi) and pipi stacking
      interactions play critical roles in the formation of an extended supramolecular
      array. The combination of C-Hpi and pipi stacking interactions endow 1 with a 3D
      network. 2 displays a rare 3D structure with a unique 1D structure based on an
      eight-membered {Ag2C2O4} ring and compound 3 shows a 1D chain structure, which is
      propagated to form an extended 3D structure only by C-Hpi hydrogen bonding. The
      two Ag(i)-compounds display blue emissions in the solid state at 298 K and 77 K.
      More significantly, compound 1 shows excellent selectivity, fast detection time
      (<5 min), and high sensitivity (detection limit, 9.63 nM) for Hg2+ ions in
      aqueous solution due to a great enhancement of 1-luminescence, which can be
      attributed to Hg2+ cation binding by a non-coordinated carboxyl group
      efficiently. This is a rare example of Hg2+ detection in aqueous solution based
      on luminescent silver MOAs. In addition, adsorption spectra reveal the
      semiconductive nature (2.76 eV for 2, but not detected for 1), thus the role of
      the AgAg interaction in controlling the performance of the semiconductor
      properties is highlighted.

PMID- 27711747
TI  - The first example of ab initio calculations of f-f transitions for the case of
      [Eu(DOTP)]5- complex-experiment versus theory.
AB  - Crystal structures and photophysical properties (IR and UV-vis-NIR) of two
      compounds, [C(NH2)3]5[Eu(DOTP)].12.5H2O and K5[Eu(DOTP)].11H2O (DOTP = 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetrakis (methylenephosphonic acid)), were
      determined. The DOTP ligand is bonded to Eu3+via four O and four N atoms, filling
      thus eight coordination sites of Eu3+. The experimental structures of two
      [K4Eu(DOTP)]- clusters were used as a starting point for theoretical ab initio
      calculations based on a multireference wavefunction approach. Positions of the
      energy levels of the 4f6 configuration of the Eu3+ ion have been calculated and
      compared with those derived from the experimental spectra. This enabled us to
      tentatively assign energy levels of the Eu3+ ion. The relationship between
      calculated energies of excited states and Eu-N and Eu-O bond lengths was
      discussed with respect to the nephelauxetic effect.

PMID- 27711749
TI  - Deuterium substitution effects on the structural and magnetic phase transitions
      of a hydrogen-bonded coordination polymer, bis(glycolato)copper(ii).
AB  - Bis(glycolato)copper(ii) [Cu(HOCH2CO2)2] shows a structural phase transition
      around 220 K under cooling and 270 K under heating, and ferromagnetic ordering at
      1.1 K. Deuterium substitution of the hydroxyl groups in it induced a large shift
      in the structural transition temperature while no shift in the ferromagnetic
      transition temperature took place.

PMID- 27711748
TI  - Solution equilibria and the X-ray structure of Cu(ii) complexation with 3-amino-N
      (pyridin-2-ylmethyl)propanamide, a pseudo-mimic of human serum albumin.
AB  - Copper complexes have anti-inflammatory activity in the treatment of inflammation
      associated with rheumatoid arthritis (RA). The preferred route of administration
      is through the skin, so the rate of dermal absorption and bioavailability of
      copper is important. Based on previous studies, 3-amino-N-(pyridin-2-ylmethyl)
      propanamide, [H(56)NH2], was designed as a potential chelator of copper. The
      stability constant measurements revealed that MLH-1 is the most stable species at
      the physiological pH of 7.4. The X-ray crystal structure of this species was
      solved and copper was found in a rectangular pyramidal geometry. The ligand
      occupied three coordination sites while bridging chloride linked copper ions
      together in a chain. The ligand bound to the metal ion through the pyridyl
      nitrogen, the amide nitrogen and the terminal amino group. Spectroscopic studies
      confirmed that this structure persisted in aqueous solution. Octanol/water
      partition coefficients and Franz cell permeation studies showed that [H(56)NH2]
      is able to promote the dermal absorption of Cu(ii).

PMID- 27711750
TI  - Physical chemistry of hybrid perovskite solar cells.

PMID- 27711751
TI  - When does near-wall hindered diffusion influence mass transport towards targets?
AB  - The diffusion of a particle is slowed as it moves close to a surface. We identify
      the conditions under which this hindered diffusion is significant and show that
      is strongly dependant on the sizes of both the particle and the target. We focus
      particularly on the transport of nano-particles to a variety of targets including
      a planar surface, a sphere, a disc and a wire, and provide data which allows the
      frequency of impacts to be inferred for a variety of experimental conditions.
      Equations are given to estimate the particle fluxes and we explain literature
      observations reported on the detected frequency of impacts. Finally we observe a
      drastic effect on the calculation of the mean first passage time of a single
      particle impacting a sub-micron sized target, showing the importance of this
      effect in biological systems.

PMID- 27711752
TI  - Anti-inflammatory activity and enhanced COX-2 selectivity of nitric oxide
      donating zinc(ii)-NSAID complexes.
AB  - Zinc(ii)-NSAID complexes supported by NO-donating 1,10-phenanthrolinefuroxan
      exhibit anti-inflammatory activities through selective inhibition of the COX-2
      pathway. The strategy represents a general procedure to convert non-selective or
      COX-1 selective NSAIDs to selective COX-2 inhibitors.

PMID- 27711753
TI  - Ru nanoparticles supported on nitrogen-doped porous carbon derived from ZIF-8 as
      an efficient catalyst for the selective hydrogenation of p-chloronitrobenzene and
      p-bromonitrobenzene.
AB  - Ruthenium (Ru) nanoparticles (NPs) are supported on nitrogen-doped porous carbon
      (NPC) derived from metal-organic-framework (MOF) ZIF-8 for the first time. NPC is
      prepared by the direct carbonization of ZIF-8 crystals, which not only retains
      the original morphology of ZIF-8 but also provides a high surface area and stable
      chemical-physical properties. Ru NPs were supported by different methods. Four
      types of Ru-based catalysts are tested in the selective hydrogenation of p
      chloronitrobenzene (p-CNB) and p-bromonitrobenzene (p-BNB) to haloanilines.
      Different catalytic activities and selectivities are obtained through these
      catalysts. After the screening of the catalysts and reaction conditions, high
      conversion and selectivity were obtained. The hydrogen pressure is limited to 1.5
      MPa, which is much lower than most previous reports, and the dehalogenation
      reaction is restricted to a very low level. Furthermore, the dehalogenation
      properties of the Ru/NPC catalysts are also studied.

PMID- 27711754
TI  - Characteristics and reactivity of ruthenium-oxo complexes.
AB  - In this perspective, we have surveyed the synthetic procedure, characteristics,
      and reactivity of high-valent ruthenium-oxo complexes. The ruthenium-oxo
      complexes have served as ideal species to elucidate the characteristics of metal
      oxo complexes in terms of not only geometrical and electronic structures but also
      oxidation reactivity and mechanisms of oxidation reactions. Due to the high
      stability and excellent reversibility of redox processes, ruthenium-oxo complexes
      have provided significant mechanistic insights into the oxidation of organic
      compounds including alcohols, alkenes, and alkanes and also water on the basis of
      detailed kinetic analysis.

PMID- 27711755
TI  - Macrocyclic ligand decorated ordered mesoporous silica with large-pore and short
      channel characteristics for effective separation of lithium isotopes: synthesis,
      adsorptive behavior study and DFT modeling.
AB  - Effective separation of lithium isotopes is of strategic value which attracts
      growing attention worldwide. This study reports a new class of macrocyclic ligand
      decorated ordered mesoporous silica (OMS) with large-pore and short-channel
      characteristics, which holds the potential to effectively separate lithium
      isotopes in aqueous solutions. Initially, a series of benzo-15-crown-5 (B15C5)
      derivatives containing different electron-donating or -withdrawing substituents
      were synthesized. Extractive separation of lithium isotopes in a liquid-liquid
      system was comparatively studied, highlighting the effect of the substituent,
      solvent, counter anion and temperature. The optimal NH2-B15C5 ligands were then
      covalently anchored to a short-channel SBA-15 OMS precursor bearing alkyl halides
      via a post-modification protocol. Adsorptive separation of the lithium isotopes
      was fully investigated, combined with kinetics and thermodynamics analysis, and
      simulation by using classic adsorption isotherm models. The NH2-B15C5 ligand
      functionalized OMSs exhibited selectivity to lithium ions against other alkali
      metal ions including K(i). Additionally, a more efficient separation of lithium
      isotopes could be obtained at a lower temperature in systems with softer counter
      anions and solvents with a lower dielectric constant. The highest value
      separation factor (alpha = 1.049 +/- 0.002) was obtained in CF3COOLi aqueous
      solution at 288.15 K. Moreover, theoretical computation based on the density
      functional theory (DFT) was performed to elucidate the complexation interactions
      between the macrocyclic ligands and lithium ions. A suggested mechanism involving
      an isotopic exchange equilibrium was proposed to describe the lithium isotope
      separation by the functionalized OMSs.

PMID- 27711756
TI  - A series of dinuclear lanthanide complexes with slow magnetic relaxation for Dy2
      and Ho2.
AB  - The employment of a new Schiff base ligand, 2-{[(2-hydroxy-3
      methoxybenzyl)imino]methyl}naphthalen-1-ol (H2L), in 4f-metal chemistry has led
      to the formation of seven new isostructural lanthanide(iii) complexes. More
      specifically the 1 : 1 reaction of Ln(NO3)3.6H2O and H2L in ethanol in the
      presence of 3 equivalents of pyridine yielded seven dinuclear complexes of
      compositions [Ln2L2(NO3)2(C2H5OH)2].0.5py (Ln = Eu (1), Gd (2), Tb (3), Dy (4),
      Ho (5), Er (6), Yb (7); py = pyridine). The structures of the isomorphous
      complexes 1-7 were determined by single-crystal X-ray crystallography. X-ray
      crystallography data reveal that each compound is neutral, and contains two
      doubly-deprotonated ligands, two chelated nitrates and two coordinated ethanol
      molecules. The two LnIII atoms in 1-7 are doubly bridged by the two phenolato
      oxygen atoms of two L2- ligands. Each of the two lanthanide ions is eight
      coordinated and possesses distorted dodecahedron geometry. Dc magnetic
      susceptibility studies in the 2-300 K range reveal probably a weak
      antiferromagnetic interaction for 2, 3 and 6, and a ferromagnetic interaction at
      low temperature for 4 and 5. Complexes 4 and 5 show slow magnetic relaxation
      behavior. The Ueff for 4 of 66.7 K is a relatively high value among the reported
      Dy2 SMMs. Complex 5 is a very rare example of a Ho2 compound which exhibits slow
      magnetic relaxation.

PMID- 27711757
TI  - Highly time resolved chemical characterization of submicron organic aerosols at a
      polluted urban location.
AB  - Non-refractory submicron (NR-PM1) aerosols were measured during the late winter
      period (February-March) via an Aerodyne High Resolution Time of Flight Aerosols
      Mass Spectrometer (HR-ToF-AMS) along with Black Carbon (BC) and trace gasses in
      an industrial city, Kanpur, situated in the Gangetic Plain (GP) of India. The
      composition of NR-PM1 aerosols was dominated by organics (54%), followed by
      inorganics (36%), and BC (10%). Source apportionment via Positive Matrix
      Factorization (PMF) of AMS measured organic aerosols (OAs) revealed 6 factors.
      Factors are identified as 2 types of oxidized organic aerosols (OOAs), 2 types of
      biomass burning organic aerosols (BBOAs), freshly emitted hydrocarbon-like
      organic aerosols (HOAs) and oxygenated primary organic aerosols (OPOAs). A
      substantial increase in relative OOA contributions (200%) and O/C ratio (26%) has
      been observed from the high loading events (HLE) to the low loading events (LLE).
      Back trajectory analysis indicated that the study location received contributions
      from regional and long-range transported aerosols. OA composition and evolution
      during this study period were also very different from those observed during a
      fog influenced peak winter period of December-January. This is the first study to
      present detailed aerosol composition during the late winter period in India
      highlighting the changes in OA composition and chemistry within the same winter
      season.

PMID- 27711758
TI  - Crystal, electronic, and magnetic structures of M2AgF4 (M = Na-Cs) phases as
      viewed from the DFT+U method.
AB  - Theoretical investigations of the magneto-structural correlations of M2AgF4 (M =
      Na-Cs) compounds show that they adopt two polymorphs, the layered perovskite and
      post-perovskite structures, which differ greatly in the connectivity of the Ag/F
      sub-lattice and hence in their magnetic properties. With the use of the DFT+U
      method, the relative stabilities of various M2AgF4 phases were established and
      the collective JT effect within the Ag/F sub-lattice of these systems was
      modelled. Calculations show that for all studied stoichiometries, the preferred
      scenario of the collective JT effect in the layered perovskite phase corresponds
      to an antiferrodistortive order of elongated octahedra, which leads to 2D
      ferromagnetic coupling, in agreement with the experimental findings for the M =
      Cs, and Rb systems. The layered perovskite phase is found to be progressively
      destabilized with respect to the post-perovskite structure when moving from Cs to
      Na, again in agreement with the experimental findings. Our results strongly
      indicate that the layered polymorph of K2AgF4 should not exhibit a
      ferrodistortive order of compressed octahedra, which contradicts the previous
      experimental results.

PMID- 27711759
TI  - A computational study of doped olivine structured Cd2GeO4: local defect trapping
      of interstitial oxide ions.
AB  - Computational modelling techniques have been employed to investigate defects and
      ionic conductivity in Cd2GeO4. We show due to highly unfavourable intrinsic
      defect formation energies the ionic conducting ability of pristine Cd2GeO4 is
      extremely limited. The modelling results suggest trivalent doping on the Cd site
      as a viable means of promoting the formation of the oxygen interstitial defects.
      However, the defect cluster calculations for the first time explicitly suggest a
      strong association of the oxide defects to the dopant cations and tetrahedral
      units. Defect clustering is a complicated phenomenon and therefore not trivial to
      assess. In this study the trapping energies are explicitly quantified. The trends
      are further confirmed by molecular dynamic simulations. Despite this, the
      calculated diffusion coefficients do suggest an enhanced oxide ion mobility in
      the doped system compared to the pristine Cd2GeO4.

PMID- 27711760
TI  - A discrete Cu cluster and a 3D MnII-CuII framework based on assembly of Mn2Cu4
      clusters: synthesis, structure and magnetic properties.
AB  - The synthesis, single-crystal structure characterization and detailed magnetic
      study of a homometallic hexanuclear CuII cluster [Cu6(MU3-OH)2(ppk)6(H2O)2(NO3)4]
      (1) and a three-dimensional (3D) compound [{MnCu2(dpkO2H)2(dpkO2)N3}.(NO3).H2O]n
      (2) (ppk = phenyl-2-pyridyl ketoxime; dpk = di-2-pyridyl ketone) consisting of
      heterometallic MnII-CuII hexanuclear cores as secondary building units are
      reported in this paper. In compound 1, two symmetry-related Cu3 triangles
      consisting of a hydroxido-bridged trinuclear unit, [Cu3(MU3
      OH)(ppk)3(H2O)(NO3)]+, are assembled through nitrate bridging giving rise to the
      homometallic Cu6 cluster. Compound 2 contains heterometallic {MnCu} cores, which
      are further connected to each other through an azido bridging ligand in all the
      crystallographic directions, resulting in a 3D metal-organic framework.
      Construction of such a heterometallic 3D framework from {MnCu} units is until
      now, unknown. Magnetic studies of both 1 and 2 were performed in detail and both
      compounds show dominant antiferromagnetic interaction in the respective clusters.
      Compound 1 reveals significant spin frustration and anti-symmetric exchange
      interaction in the trinuclear cores, with a significantly high value of Jav (-655
      cm-1). Furthermore, compound 2 exhibits a dominant antiferromagnetic interaction,
      which is also supported by an extensive magneto-structural correlation which
      considers the different magnetic pathways.

PMID- 27711761
TI  - Correction: Simulations of the water exchange dynamics of lanthanide ions in 1
      ethyl-3-methylimidazolium ethyl sulfate ([EMIm][EtSO4]) and water.
AB  - Correction for 'Simulations of the water exchange dynamics of lanthanide ions in
      1-ethyl-3-methylimidazolium ethyl sulfate ([EMIm][EtSO4]) and water' by Yi-Jung
      Tu et al., Phys. Chem. Chem. Phys., 2016, DOI: 10.1039/c6cp04957e.

PMID- 27711762
TI  - Stoichiometry-controlled structural and functional variation in two photochromic
      iodoargentates with a fast and wide range response.
AB  - By using 1-methyl-4-(carbomethoxy)pyridinium (MCMP+) as counterions, two
      iodoargentate hybrids, 1D [MCMP][AgI2] (1) and 3D [MCMP][Ag3I4] (2) have been
      synthesized and they exhibit rare electron transfer photochromism with a fast
      response rate, a wide response range and a long-lived charge-separated state in
      iodometallate systems. Noteworthily, the marked differences in the structure and
      photochromic performance of 1 and 2 are largely ascribed to the different
      aggregating behavior of electron-deficient MCMP+ counterions (C-HO hydrogen
      bonded trimer in 1 and pi-pi/C-Hpi chain in 2).

PMID- 27711763
TI  - Solid-state study of the structure and host-guest chemistry of cucurbituril
      ferrocene inclusion complexes.
AB  - Inclusion complexes of ferrocene (Fc) with cucurbit[n]urils (n = 7, 8) have been
      prepared via a rapid microwave-assisted hydrothermal approach. Solids were
      isolated and characterised by elemental analysis, powder X-ray diffraction
      (PXRD), spectroscopic, and thermoanalytical methods. The UV-Vis spectra support
      the presence of Fc in Fc@CB7 and a mixture of Fc and ferrocenium ions in Fc@CB8.
      Partial oxidation of Fc to Fc+ takes place in situ mainly due to the presence of
      acid of crystallisation in CB8. On the basis of PXRD, the complex Fc@CB8 is
      classified into an isostructural series that is formed by several CB8-containing
      compounds that crystallise in the space group I41/a and have similar unit cell
      dimensions and CB8 packing motifs. The FT-IR and Raman spectra of Fc@CB7 are
      compared with those of the CB7 host and the Fc guest starting materials,
      revealing significant frequency shifts of some Fc-centered vibrational modes upon
      complexation. Blueshifts of the Fe-Cp stretching and ring tilt bands are
      attributed to encapsulation of Fc monomers in a constrained environment, leading
      to restricted motion effects and/or a change in the Fc conformation from
      staggered to eclipsed. The absence of comparable shifts for Fc@CB8 point to a
      weaker host-guest interaction as a consequence of the larger cavity size. The
      different host-guest interactions are also evident through a comparison of the
      13C{1H} CP MAS NMR spectra. Thermogravimetric analysis for the inclusion
      compounds reveals that sublimation of Fc is inhibited by molecular encapsulation
      to the extent that oxidative decomposition of the organoiron species takes place
      concurrently with cucurbituril decomposition, leading to the formation of
      hematite, alpha-Fe2O3.

PMID- 27711764
TI  - Increasing the triplet lifetime and extending the ground-state absorption of
      biscyclometalated Ir(iii) complexes for reverse saturable absorption and
      photodynamic therapy applications.
AB  - The synthesis, photophysics, reverse saturable absorption, and photodynamic
      therapeutic effect of six cationic biscyclometalated Ir(iii) complexes (1-6) with
      extended pi-conjugation on the diimine ligand and/or the cyclometalating ligands
      are reported in this paper. All complexes possess ligand-localized 1pi,pi*
      absorption bands below 400 nm and charge-transfer absorption bands above 400 nm.
      They are all emissive in the 500-800 nm range in deoxygenated solutions at room
      temperature. All complexes exhibit strong and broad triplet excited-state
      absorption at 430-800 nm, and thus strong reverse saturable absorption for ns
      laser pulses at 532 nm. Complexes 1-4 are strong reverse saturable absorbers at
      532 nm, while complex 6 could be a good candidate as a broadband reverse
      saturable absorber at 500-850 nm. The degree of pi-conjugation of the diimine
      ligand mainly influences the 1pi,pi* transitions in their UV-vis absorption
      spectra, while the degree of pi-conjugation of the cyclometalating ligand
      primarily affects the nature and energies of the lowest singlet and emitting
      triplet excited states. However, the lowest-energy triplet excited states for
      complexes 3-6 that contain the same benzo[i]dipyrido[3,2-a:2',3'-c]phenazine
      (dppn) diimine ligand but different cyclometalating ligands remain the same as
      the dppn ligand-localized 3pi,pi* state, which gives rise to the long-lived,
      strong excited-state absorption in the visible to the near-IR region. All of the
      complexes exhibit a photodynamic therapeutic effect upon visible or red light
      activation, with complex 6 possessing the largest phototherapeutic index reported
      to date (>400) for an Ir(iii) complex. Interactions with biological targets such
      as DNA suggest that a novel mechanism of action may be at play for the
      photosensitizing effect. These Ir(iii) complexes also produce strong
      intracellular luminescence that highlights their potential as theranostic agents.

PMID- 27711765
TI  - CRISPR/Cas9: a historical and chemical biology perspective of targeted genome
      engineering.
AB  - The CRISPR-Cas9 system has revolutionized the process of making changes to the
      DNA sequence of organisms. Relying on a simplistic model of RNA guided DNA
      binding and cleavage, this molecular toolbox has found application in nearly
      every branch of biological sciences. The story of CRISPR-Cas9 is one of discovery
      and development where a component of bacterial adaptive immunity has been
      harnessed to address important biological questions using significant inputs from
      physicochemical structure-function studies. In this review, we trace the
      evolution of CRISPR-Cas9 from its predecessor genome editing tools and document
      its current status with an emphasis on chemical biology aspects of modulating its
      activity to generate a potent tool for gene therapy applications.

PMID- 27711767
TI  - The {Ni10Nb32} aggregate: a perspective on isopolyniobates as ligands.
AB  - [H4Ni10(H2O)8Nb32O102]20-, representing the first high-nuclear nickel-cation
      bridged polyoxoniobate, has been synthesized. It incorporates two
      [{Ni2O4}(H2O)2(Nb6O19)]12- and two [Ni3(H2O)2Nb10O34]12- subunits exhibiting a
      rhombus-like architecture. Furthermore, the solution behaviour was examined by
      electrospray ionization mass spectrometry and the magnetic properties in the low
      temperature range indicate the presence of ferromagnetic interactions.

PMID- 27711768
TI  - Three and four coordinate Fe carbodiphosphorane complexes.
AB  - Carbodiphosphoranes (CDPs) are a family of divalent carbon ligands that are known
      for their exceptional electron donor properties. Herein, the preparation and
      reactivity of a family of three and four co-ordinate Fe carbodiphosphorane
      complexes is described. Hexaphenylcarbodiphosphorane (HCDP) [1] is shown to react
      with FeCl2(PPh3)2 to form the three coordinate adduct Fe(HCDP)Cl2 [2], which is
      equilibrium with its four coordinate dimer. Reaction of [2] with two equivalents
      of benzyl Grignard yields the corresponding dialkyl complex (HCDP)FeBn2 [3].
      Combination of [2] with LiHMDS results in salt metathesis and the formation of
      the monosilylated derivative Fe(HCDP)Cl(N(SiMe3)2) [4]. Subsequent anion exchange
      leads to the three coordinate Fe(HCDP)(OTf)(N(SiMe3)2) [5] which was
      characterized crystallographically and in solution.

PMID- 27711766
TI  - Cyclometallated iridium complexes inducing paraptotic cell death like natural
      products: synthesis, structure and mechanistic aspects.
AB  - Six mononuclear Ir complexes (1-6) using polypyridyl-pyrazine based ligands (L1
      and L2) and {[cp*IrCl(MU-Cl)]2 and [(ppy)2Ir(MU-Cl)]2} precursors have been
      synthesised and characterised. Complexes 1-5 have shown potent anticancer
      activity against various human cancer cell lines (MCF-7, LNCap, Ishikawa, DU145,
      PC3 and SKOV3) while complex 6 is found to be inactive. Flow cytometry studies
      have established that cellular accumulation of the complexes lies in the order 2
      > 1 > 5 > 4 > 3 > 6 which is in accordance with their observed cytotoxicity. No
      changes in the expression of the proteins like PARP, caspase 9 and beclin-1,
      Atg12 discard apoptosis and autophagy, respectively. Overexpression of CHOP,
      activation of MAPKs (P38, JNK, and ERK) and massive cytoplasmic vacuolisation
      collectively suggest a paraptotic mode of cell death induced by proteasomal
      dysfunction as well as endoplasmic reticulum and mitochondrial stress. An
      intimate relationship between p53, ROS production and extent of cell death has
      also been established using p53 wild, null and mutant type cancer cells.

PMID- 27711769
TI  - Small molecule activation.

PMID- 27711770
TI  - Chromium complexes bearing amidinato-phosphino ligand: synthesis,
      characterization, and catalytic properties of ethylene tri-/tetramerization and
      polymerization.
AB  - An amidinato-phosphino ligand ArN[double bond, length as m-dash]C(R)NH(o
      Ph2PC6H4) (Ar = 2,4,6-Me3C6H2, R = Ph (1); Ar = 2,6-iPr2C6H3, R = Ph (2); Ar =
      2,6-iPr2C6H3, R = tBu (3)) was prepared. The ligand reacted with CrCl3(THF)3 to
      yield the N,P-chelation complex [ArNHC(R)[double bond, length as m-dash]N(o
      Ph2PC6H4)]CrCl3(THF) (4-6), and the ligand's lithium salt ArN[double bond, length
      as m-dash]C(R)N(o-Ph2PC6H4)Li reacted with the respective CrCl3(THF)3 and
      CrCl2(THF)2 to give the N,N,P-chelation complexes [ArN[double bond, length as m
      dash]C(R)N(o-Ph2PC6H4)]CrCl2(THF) (7-8) and {[ArN[double bond, length as m
      dash]C(R)N(o-Ph2PC6H4)]Cr(MU-Cl)}2 (9-11). Complexes 1-11 were characterized by
      IR, NMR (for 1-3), EPR (for 4-11) spectroscopy and CHN elemental analysis, of
      which 3, 5, 8, and 11 were further studied by X-ray crystallography. Upon
      activation with an organoaluminum cocatalyst, complexes 4-6 were all
      catalytically active in ethylene tri-/tetramerization along with ethylene
      polymerization, and complexes 7-11 functioned as well but in ethylene
      polymerization. The correlation between the structure and the catalytic
      properties of the catalyst system is discussed.

PMID- 27711771
TI  - Pseudocontact shifts from mobile spin labels.
AB  - This paper presents a detailed analysis of the pseudocontact shift (PCS) field
      induced by a mobile spin label that is viewed as a probability density
      distribution with an associated effective magnetic susceptibility anisotropy. It
      is demonstrated that non-spherically symmetric density can lead to significant
      deviations from the commonly used point dipole approximation for the PCS.
      Analytical and numerical solutions are presented for the general partial
      differential equation that describes the non-point case. It is also demonstrated
      that it is possible, with some reasonable approximations, to reconstruct
      paramagnetic centre probability distributions from the experimental PCS data.

PMID- 27711772
TI  - Boron complexes of aromatic ring fused iminopyrrolyl ligands: synthesis,
      structure, and luminescence properties.
AB  - The condensation reactions of 2-formylindole (1) or 2-formylphenanthro[9,10
      c]pyrrole (2) with various aromatic amines afforded the corresponding phenyl or
      phenanthrene ring fused mono-/bis-iminopyrrole ligand precursors 3-8, which, upon
      reaction with BPh3 in an appropriate molar ratio, led to the new mono- and
      diboron chelate compounds Ph2B[NC8H5C(H)[double bond, length as m-dash]N-2,6-Ar]
      (Ar = 2,6-iPr2C6H39; C6H510), Ph2B[(NC8H5C(H)[double bond, length as m-dash]N)2
      1,4-C6H4]BPh211, Ph2B(NC16H9C(H)[double bond, length as m-dash]N-Ar) (Ar = 2,6
      iPr2C6H312; C6H513), and Ph2B[(NC16H9C(H)[double bond, length as m-dash]N)2-1,4
      C6H4]BPh214, respectively. Boron complexes 12-14, containing a phenanthrene
      fragment fused to the pyrrolyl C3-C4 bond, are highly fluorescent in solution,
      with quantum efficiencies of 37%, 61% and 58% (in THF), respectively, their
      emission colours ranging from blue to orange depending on the extension of pi
      conjugation. Complexes 9-11, containing a benzene fragment fused to the pyrrolyl
      C4-C5 bond, are much weaker emitters, exhibiting quantum efficiencies of 10%, 7%
      and 6%, respectively. DFT and TDDFT calculations showed that 2,6-iPr2C6H3N
      substituents or, to a smaller extent, the indolyl group prevent a planar geometry
      of the ligand in the excited state and reveal the existence of a low energy weak
      band in all the indolyl complexes, which is responsible for the different optical
      properties. Non-doped single-layer light-emitting diodes (OLEDs) were fabricated
      with complexes 9-14, deposited by spin coating, that of complex 13 revealing a
      maximum luminance of 198 cd m-2.

PMID- 27711773
TI  - An unusual assembled Pb(ii) meso-helicate that shows the inert pair effect.
AB  - A dinuclear Pb(ii) mesocate has been prepared with an unprecedented four
      coordinated kernel in which the Pb(ii) lone pair is stereochemically active. This
      is the first time that this effect has been observed in a supramolecular Pb(ii)
      helicate or meso-helicate.

PMID- 27711774
TI  - 1001 lights: luciferins, luciferases, their mechanisms of action and applications
      in chemical analysis, biology and medicine.
AB  - Bioluminescence (BL) is a spectacular phenomenon involving light emission by live
      organisms. It is caused by the oxidation of a small organic molecule, luciferin,
      with molecular oxygen, which is catalysed by the enzyme luciferase. In nature,
      there are approximately 30 different BL systems, of which only 9 have been
      studied to various degrees in terms of their reaction mechanisms. A vast range of
      in vitro and in vivo analytical techniques have been developed based on BL,
      including tests for different analytes, immunoassays, gene expression assays,
      drug screening, bioimaging of live organisms, cancer studies, the investigation
      of infectious diseases and environmental monitoring. This review aims to cover
      the major existing applications for bioluminescence in the context of the
      diversity of luciferases and their substrates, luciferins. Particularly, the
      properties and applications of d-luciferin, coelenterazine, bacterial, Cypridina
      and dinoflagellate luciferins and their analogues along with their corresponding
      luciferases are described. Finally, four other rarely studied bioluminescent
      systems (those of limpet Latia, earthworms Diplocardia and Fridericia and higher
      fungi), which are promising for future use, are also discussed.

PMID- 27711775
TI  - Dehalogenation of chloroalkanes by nickel(i) porphyrin derivatives, a
      computational study.
AB  - The nickel(i) octaethylisobacteriochlorin anion ([OEiBCh-Ni(I)]-) is commonly
      used as a synthetic model of cofactor F430 from Methyl-Coenzyme M Reductase. In
      this regard, experimental studies show that [OEiBCh-Ni(I)]- can catalyze
      dehalogenation of aliphatic halides in DMF solution by a highly efficient SN2
      reaction. To better understand this process, we constructed theoretical models of
      the dehalogenation of chloromethane by a simple nickel(i) isobacteriochlorin
      anion and compared its reactivity with that of similar Ni(I) complexes with other
      porphyrin-derived ligands: porphyrin, chlorin, bactreriochlorin,
      hexahydroporphyrin and octahydroporphyrin. Our calculations predict that all of
      the porphyrin derivative's model reactions proceed through low-spin complexes.
      Relative to the energy of the separate reactants the theoretical activation
      energies (free-energy barriers with solvation corrections) for the dehalogenation
      of chloromethane are similar for all of the porphyrin derivatives and range for
      the different functionals from 10-15 kcal mol-1 for B3LYP to 5-10 kcal mol-1 for
      M06-L and to 13-18 kcal mol-1 for omegaB97X-D. The relative free energies of the
      products of the dehalogenation step, L-Ni-Me adducts, have a range from -5 to -40
      kcal mol-1 for all functionals; generally becoming more negative with increasing
      saturation of the porphyrin ligand. Moreover, no significant differences in the
      theoretical chlorine kinetic isotope effect were discernable with change of
      porphyrin ligand.

PMID- 27711776
TI  - Thermodynamics of biphasic lanthanide extraction by tripodal diglycolamide: a
      solution calorimetry study.
AB  - Isothermal titration calorimetry was employed for the direct measurement of the
      enthalpy of extraction (DeltaHextr) of Eu(NO3)3 by using a tripodal diglycolamide
      (T-DGA) ligand dissolved in n-dodecane containing 5% (v/v) 2-decanol. The
      enthalpy of extraction obtained by titration calorimetry was in good agreement
      with the enthalpy of extraction calculated from the temperature dependence of the
      distribution coefficients by using the van't Hoff equation. The Gibbs free energy
      and the entropy of extraction (DeltaGextr and DeltaSextr) for the extraction of
      Eu(NO3)3 by T-DGA were also obtained by solvent extraction experiments. The
      complexation of Eu3+ with T-DGA in a mixture of acetonitrile/nitric acid was also
      studied by spectrophotometry and calorimetry to determine the stability constants
      and the enthalpy of complexation (DeltaHcomp) for the Eu3+/T-DGA complexes in a
      single phase. The enthalpy of complexation, though obtained in a solvent
      different from that in the solvent extraction, allows a rough estimate of the
      enthalpy of phase transfer of the Eu3+/T-DGA complexes from the aqueous phase to
      the organic phase.

PMID- 27711777
TI  - Self-assembled dimethyldihydropyrene-pyridyl substituted ligands with zinc(ii)
      meso-tetraphenylporphyrin via axial coordination.
AB  - A series of dimethyldihydropyrene (DHP)-pyridyl photochromic derivatives has been
      synthesized and its photochemical behaviour characterized by spectroscopic and
      electrochemical methods. The corresponding noncovalently-linked electron donor
      acceptor complexes have been isolated. They combine the DHP-pyridyl ligand as a
      donor and the zinc(ii) tetraphenylporphyrin as acceptor. Such association allowed
      to explore the efficiency of dative bonds to monitor the interactions between the
      two units.

PMID- 27711778
TI  - Interference stabilization of autoionizing states in molecular N2 studied by time
      and angular-resolved photoelectron spectroscopy.
AB  - An autoionizing resonance in molecular N2 is excited by an ultrashort XUV pulse
      and probed by a subsequent weak IR pulse, which ionizes the contributing Rydberg
      states. Time- and angular-resolved photoelectron spectra recorded with a velocity
      map imaging spectrometer reveal two electronic contributions with different
      angular distributions. One of them has an exponential decay rate of 20 +/- 5 fs,
      while the other one is shorter than 10 fs. This observation is interpreted as a
      manifestation of interference stabilization involving the two overlapping
      discrete Rydberg states. A formalism of interference stabilization for molecular
      ionization is developed and applied to describe the autoionizing resonance. The
      results of calculations suggest, that the effect of the interference
      stabilization is facilitated by rotationally-induced couplings of electronic
      states with different symmetry.

PMID- 27711779
TI  - Oxygen reduction reaction catalyzed by nickel complexes based on
      thiophosphorylated calix[4]resorcinols and immobilized in the membrane electrode
      assembly of fuel cells.
AB  - The catalytic activity of the nickel complexes of thiophosphorylated
      calix[4]resorcinols for oxygen reduction in a polymer electrolyte membrane fuel
      cell (PEMFC) has been studied. The conformation of the macrocyclic ligand
      determines the morphology and catalytic properties of the resulting
      organometallic species.

PMID- 27711780
TI  - Synthesis of three series of ruthenium tris-diimine complexes containing acridine
      based pi-extended ligands using an efficient "chemistry on the complex" approach.
AB  - The preparation and characterization of three series of novel ruthenium(ii)
      complexes are reported, each series differing by the nature of the ancillary
      ligands (2,2'-bipyridine - bpy, 1,10-phenanthroline - phen or 1,4,5,8
      tetraazaphenanthrene - TAP). The third ligand was either the heptacyclic
      heterocycle dipyrido[3,2-a:2',3'-c]quinolino[3,2-h]phenazine (dpqp) substituted
      at position 12 by an hydroxyl (oxo), 2,2-dimethoxyethylamine (DMEA) or halogeno
      (Cl or Br) substituent, or the octacyclic dipyrido[3,2-a:2',3'-c]pyrido[2,3,4
      de]quinolino[3,2-h]phenazine (dppqp), prepared by a multi-step "chemistry on the
      complex" strategy from [RuL2(oxo-dpqp)](PF6)2. The three steps, halogenation,
      substitution by a dimethoxyethylamino group and cyclization in trifluoroacetic
      acid, were performed in reasonable to high yields depending on the nature of the
      ancillary ligands. Isolation and purification processes were facilitated by the
      ability to switch the solubility of the complex from aqueous to organic solvents,
      depending on the counter-ion. All new complexes were fully characterized; in
      particular their absorption properties were compared by UV-vis spectroscopy.
      Finally, pi-stacking properties induced by these extended ligands were studied by
      1H NMR studies and quantum chemical calculations.

PMID- 27711781
TI  - Plasma engineering of silicon quantum dots and their properties through energy
      deposition and chemistry.
AB  - The characterization of plasma and atomic radical parameters along with the
      energy influx from plasma to the substrate during plasma enhanced chemical vapor
      deposition (PECVD) of Si quantum dot (QD) films is presented and discussed. In
      particular, relating to the Si QD process optimization and control of film
      growth, the necessity to control the deposition environment by inducing the
      effect of the energy of the key plasma species is realized. In this contribution,
      we report dual frequency PECVD processes for the low-temperature and high-rate
      deposition of Si QDs by chemistry and energy control of the key plasma species.
      The dual frequency plasmas can effectively produce a very high plasma density and
      atomic H and N densities, which are found to be crucial for the growth and
      nucleation of QDs. Apart from the study of plasma chemistry, the crucial role of
      the energy imparted due to these plasma activated species on the substrate is
      determined in light of QD formation. Various plasma diagnostics and film analysis
      methods are integrated to correlate the effect of plasma and energy flux on the
      properties of the deposited films prepared in the reactive mixtures of SiH4/NH3
      at various pressures. The present results are highly relevant to the development
      of the next-generation plasma process for devices that rely on effective control
      of the QD size and film properties.

PMID- 27711782
TI  - Visible-light-induced release of CO by thiolate iron(iii) carbonyl complexes
      bearing N,C,S-pincer ligands.
AB  - Iron(iii) carbonyl complexes are stabilized by a pincer ligand containing
      pyridine-N, phenyl-C and thiolate-S donors and two axial phosphine ligands. The
      N,C,S-pincer iron(iii) carbonyl complexes show CO-releasing properties induced by
      visible light.

PMID- 27711783
TI  - Multifunctional Eu-doped NaGd(MoO4)2 nanoparticles functionalized with poly(l
      lysine) for optical and MRI imaging.
AB  - A method for the synthesis of non-aggregated and highly uniform Eu3+ doped
      NaGd(MoO4)2 nanoparticles is reported for the first time. The obtained particles
      present tetragonal structure, ellipsoidal shape and their size can be varied by
      adjusting the experimental synthesis parameters. These nanoparticles, which were
      coated with citrate anions and functionalised with PLL, have also been developed
      in order to improve their colloidal stability in physiological medium (2-(N
      morpholino)ethanesulfonic acid, MES). A study of the luminescent dynamics of the
      samples as a function of the Eu doping level has been conducted in order to find
      the optimum nanophosphors, whose magnetic relaxivity and cell viability have also
      been evaluated for the first time for this system, in order to assess their
      suitability as multifunctional probes for optical (in vitro) and magnetic
      bioimaging applications.

PMID- 27711784
TI  - Visualization of bond rearrangements in acetylene using near single-cycle laser
      pulses.
AB  - The migration of hydrogen atoms resulting in the isomerization of hydrocarbons is
      an important process which can occur on ultrafast timescales. Here, we visualize
      the light-induced hydrogen migration of acetylene to vinylidene in an ionic state
      using two synchronized 4 fs intense laser pulses. The first pulse induces
      hydrogen migration, and the second is used for monitoring transient structural
      changes via Coulomb explosion imaging. Varying the time delay between the pulses
      reveals the migration dynamics with a time constant of 54 +/- 4 fs as observed in
      the H+ + H+ + CC+ channel. Due to the high temporal resolution, vibrational wave
      packet motions along the CC- and CH-bonds are observed. Even though a maximum in
      isomerization yield for kinetic energy releases above 16 eV is measured, we find
      no indication for a backwards isomerization - in contrast to previous
      measurements. Here, we propose an alternative explanation for the maximum in
      isomerization yield, namely the surpassing of the transition state to the
      vinylidene configuration within the excited dication state.

PMID- 27711785
TI  - The effect of imidazole on the enhancement of gadolinium-porphyrin
      phosphorescence at room temperature.
AB  - A mechanism for the enhanced room-temperature phosphorescence (RTP) of gadolinium
      coordinated hematoporphyrin monomethyl ether (Gd-HMME) in the presence of
      imidazole and free gadolinium ions (Gd3+) is revealed. Imidazole, the molten
      solvent used in the synthesis of Gd-HMME, was effective in enhancing the Gd-HMME
      RTP. In the presence of imidazole, further enhancement of the Gd-HMME RTP was
      observed upon adding Gd3+. Overall, a 40-fold enhancement of Gd-HMME RTP
      intensity was achieved by adding both imidazole and Gd3+. In addition, there was
      an increase in the RTP lifetime. Through spectroscopic analysis, we deduced that
      a protective medium is formed by the imidazole and the degree of this protection
      is further increased by Gd3+. The protective medium enhances the Gd-HMME RTP by
      partially inhibiting energy transfer from the lowest triplet state of Gd-HMME to
      oxygen. This was demonstrated by the presence of lower levels of singlet oxygen
      in the Gd-HMME solution after the addition of imidazole. These results indicate
      that imidazole could have potential application as an RTP enhancer or triplet
      state protector.

PMID- 27711786
TI  - Quantitative extraction of Rh(iii) using ionic liquids and its simple separation
      from Pd(ii).
AB  - The extraction of Pd(ii) and Rh(iii) from acidic solutions containing between 1
      and 8 M HCl towards three ionic liquids, namely [P66614][Cl], [P66614][Br] and
      [P66614][DCA], based on the trihexyltetradecylphosphonium cation ([P66614]) and
      chloride, bromide or dicyanamide (DCA) anions, respectively, is reported.
      Extraction of Pd(ii) is quantitative up to 6 M HCl (D > 3000). A value of 258 for
      the distribution coefficient of Rh(iii) extracted from 1 M HCl towards
      [P66614][Br] is also reported. [P66614][Cl] and [P66614][Br] were found to be
      very efficient at separating these two metals from aqueous solutions containing
      at least 6 mol L-1 HCl.

PMID- 27711788
TI  - Facile preparation of C, N co-modified Nb2O5 nanoneedles with enhanced visible
      light photocatalytic activity.
AB  - C, N co-modified niobium pentoxide (Nb2O5) nanoneedles have been successfully
      synthesized via a facile hydrothermal method with Niobium Chloride (NbCl5) as a
      precursor and triethylamine as both the carbon and nitrogen source. The formation
      process of Nb2O5 nanoneedles has been presented in detail by investigating the
      effect of the crystallization temperature, the amount of triethylamine and the
      calcination temperature. The as-prepared Nb2O5 nanoneedles exhibit more efficient
      photocatalytic activity than commercial Degussa P25 and commercial Nb2O5 towards
      photodegradation of Rhodamine B (RhB) at a concentration of 10 mg L-1 under
      visible light. Special chemical species, such as carbonate species and NOX
      species, that exist on the surface of the as-prepared catalyst could extend the
      absorption into the visible region and thus enhance the photocatalytic activity
      of the Nb2O5 nanoneedles. At the same time, the obtained Nb2O5 nanoneedles
      exhibit excellent stability even after three successive cycles. A possible
      photodegradation mechanism was proposed and the corresponding photodecomposition
      process of RhB over the Nb2O5 nanoneedles was elucidated by a reactive species
      trapping experiment, suggesting that h+ and O2- play a major role in the
      photodegradation of RhB in aqueous solution.

PMID- 27711789
TI  - Nickel silicotungstate-decorated Pt photocathode as an efficient catalyst for
      triiodide reduction in dye-sensitized solar cells.
AB  - A new type of polyoxometalate material, K6SiW11O39Ni(H2O).xH2O (denoted as
      SiW11Ni), was successfully synthesized and introduced to a dye-sensitized solar
      cell (DSSC) with modified traditional Pt as a novel composite counter electrode.
      The new counter electrode showed superior electrochemical catalytic activity for
      the reduction of I3- to I- in analysis utilizing a Tafel-polarization curve,
      cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The
      DSSC assembled with the SiW11Ni/Pt photocathode exhibited an enhanced performance
      (7.03%) under the standard AM 1.5G illumination compared to the DSSC with a
      pristine Pt photocathode (6.65%). Furthermore, the DSSC based on the SiW11Ni/Pt
      photocathode had an increased light-harvesting efficiency and was very stable.
      The results demonstrate that SiW11Ni/Pt is an alternative and highly efficient
      counter electrode for dye-sensitized solar cells. Moreover, the facile design
      strategy is promising for fabricating efficient and inexpensive composite counter
      electrode catalysts for DSSCs.

PMID- 27711787
TI  - Effects of a nanoceria fuel additive on the physicochemical properties of diesel
      exhaust particles.
AB  - Nanoceria (i.e., CeO2 nanoparticles) fuel additives have been used in Europe and
      elsewhere to improve fuel efficiency. Previously we have shown that the use of a
      commercial fuel additive EnviroxTM in a diesel-powered electricity generator
      reduced emissions of diesel exhaust particle (DEP) mass and other pollutants.
      However, such additives are currently not permitted for use in on-road vehicles
      in North America, largely due to limited data on the potential health impact. In
      this study, we characterized a variety of physicochemical properties of DEPs
      emitted from the same engine. Our methods include novel techniques such as Raman
      spectrometry for analyzing particle surface structure and an assay for DEP
      oxidative potential. Results show that with increasing EnviroxTM concentrations
      in the fuel (0*, 0.1*, 1*, and 10* of manufacturer recommended 0.5 mL EnviroxTM
      per liter fuel), DEP sizes decreased from 194.6 +/- 20.1 to 116.3 +/- 14.8 nm;
      the zeta potential changed from -28.4 mV to -22.65 mV; DEP carbon content
      decreased from 91.8% to 79.4%; cerium and nitrogen contents increased from 0.3%
      to 6.5% and 0.2% to 0.6%, respectively; the ratio of organic carbon (OC) to
      elemental carbon (EC) increased from 22.9% to 38.7%; and the ratio of the
      disordered carbon structure to the ordered carbon structure (graphitized carbon)
      in DEPs decreased. Compared to DEPs emitted from 0*, 0.1*, and 1* fuels, DEPs
      from the 10* fuel had a lower oxidative potential likely due to the increased
      ceria content because pure ceria nanoparticles exhibited the lowest oxidative
      potential compared to all the DEPs. Since the physicochemical parameters tested
      here are among the determinants of particle toxicity, our findings imply that
      adding ceria nanoparticles into diesel may alter the toxicity of DEPs. The
      findings from the present study, hence, can help future studies that will examine
      the impact of nanoceria additives on DEP toxicities.

PMID- 27711790
TI  - Intrinsic reactivity of a uranium metallacyclopropene toward unsaturated organic
      molecules.
AB  - The uranium metallacyclopropene (eta5-C5Me5)2U[eta2-C2(SiMe3)2] (1) reacts with
      various small unsaturated organic molecules. For example, replacement of
      bis(trimethylsilyl)acetylene occurs when complex 1 is exposed to alkynes,
      conjugated alkenes, nitriles and quinones. Reaction of 1 with internal
      phenyl(alkyl)acetylene PhC[triple bond, length as m-dash]CMe selectively yields
      the Cs symmetric uranium metallacyclopentadiene (eta5-C5Me5)2U[eta2-C(Ph)[double
      bond, length as m-dash]C(Me)-C(Ph)[double bond, length as m-dash]C(Me)] (6) after
      the loss of bis(trimethylsilyl)acetylene, while treatment of 1 with
      phenyl(silyl)acetylenes (PhC[triple bond, length as m-dash]CR, R = SiHMe2, SiMe3)
      gives the corresponding C2v symmetric isomers (eta5-C5Me5)2U[eta2-C(R)[double
      bond, length as m-dash]C(Ph)-C(Ph)[double bond, length as m-dash]C(R)] (R =
      SiHMe2 (7), SiMe3 (8)). Furthermore, while no deprotonation occurs between
      complex 1 and pyridine derivatives, cyclohexanone can be inserted into the
      uranium metallacyclopropene moiety of 1 to yield the five-membered, heterocyclic
      complex (eta5-C5Me5)2U[OC(CH2)5(C2(SiMe3)2)] (14) in quantitative conversion.
      Density functional theory (DFT) studies have been performed to complement the
      experimental studies.

PMID- 27711791
TI  - Towards controlling the dissociation probability by light-induced conical
      intersections.
AB  - Light-induced conical intersections (LICIs) can be formed both by standing or by
      running laser waves. The position of a LICI is determined by the laser frequency
      while the laser intensity controls the strength of the nonadiabatic coupling.
      Recently, it was shown within the LICI framework that linearly chirped laser
      pulses have an impact on the dissociation dynamics of the D2+ molecule (J. Chem.
      Phys., 143, 014305, (2015); J. Chem. Phys., 144, 074309, (2016)). In this work we
      exploit this finding and perform calculations using chirped laser pulses in which
      the time dependence of the laser frequency is designed so as to force the LICI to
      move together with the field-free vibrational wave packet as much as possible.
      Since nonadiabaticity is strongest in the vicinity of the conical intersection,
      this is the first step towards controlling the dissociation process via the LICI.
      Our showcase example is again the D2+ molecular ion. To demonstrate the impact of
      the LICIs on the dynamical properties of diatomics, the total dissociation
      probabilities and the population of the different vibrational levels after the
      dissociation process are studied and discussed.

PMID- 27711792
TI  - Triple molybdate scheelite-type upconversion phosphor NaCaLa(MoO4)3:Er3+/Yb3+:
      structural and spectroscopic properties.
AB  - Triple molybdate NaCaLa(1-x-y)(MoO4)3:xEr3+,yYb3+ (x = y = 0, x = 0.05 and y =
      0.45, x = 0.1 and y = 0.2, x = 0.2 and y = 0) phosphors were successfully
      synthesized for the first time by the microwave sol-gel method. Well-crystallized
      particles formed after heat treatment at 900  degrees C for 16 h showed a fine
      and homogeneous morphology with particle sizes of 2-3 MUm. The structures were
      refined by the Rietveld method in the space group I41/a. The optical properties
      were examined comparatively using photoluminescence emission and Raman
      spectroscopy. Under excitation at 980 nm, the NaCaLa0.7(MoO4)3:0.1Er3+,0.2Yb3+
      and NaCaLa0.5(MoO4)3:0.05Er3+,0.45Yb3+ particles exhibited a strong 525 nm
      emission band, a weaker 550 nm emission band in the green region, and three weak
      655 nm, 490 nm and 410 nm emission bands in the red, blue and violet regions. The
      pump power dependence and Commission Internationale de L'Eclairage chromaticity
      of the upconversion emission intensity were evaluated in detail.

PMID- 27711793
TI  - 3D Co3O4@MnO2 heterostructures grown on a flexible substrate and their
      applications in supercapacitor electrodes and photocatalysts.
AB  - In this work, flexible 3D Co3O4@MnO2 heterostructures have been successfully
      obtained without using any surfactants. The as-prepared flexible electrodes
      exhibit high efficiency, high discharge areal capacitance (1397.2 mF cm-2 at 1 mA
      cm-2), long cycle life (13.9% loss after 6000 repetitive cycles at 1 mA cm-2) and
      excellent electrical stability. In addition, hybrid 3D Co3O4@MnO2 structures are
      also used as photocatalysts for the photocatalytic degradation of several harmful
      organic dyes under visible light illumination. The results show that the as-grown
      products possess excellent photocatalytic performance, demonstrating their
      potential applications in wastewater treatment.

PMID- 27711794
TI  - Solution or solid - it doesn't matter: visible light-induced CO release
      reactivity of zinc flavonolato complexes.
AB  - Two types of zinc flavonolato complexes ([(6-Ph2TPA)Zn(flavonolato)]ClO4 and
      Zn(flavonolato)2) of four extended flavonols have been prepared, characterized,
      and evaluated for visible light-induced CO release reactivity. Zinc coordination
      of each flavonolato anion results in a red-shift of the lowest energy absorption
      feature and in some cases enhanced molar absorptivity relative to the free
      flavonol. The zinc-coordinated flavonolato ligands undergo visible light-induced
      CO release with enhanced reaction quantum yields relative to the neutral
      flavonols. Most notable is the discovery that both types of zinc flavonolato
      derivatives undergo similar visible light-induced CO release reactivity in
      solution and in the solid state. A solid film of a Zn(flavonolato)2 derivative
      was evaluated as an in situ CO release agent for aerobic oxidative palladium
      catalyzed alkoxycarbonylation to produce esters in ethanol. The CO release
      product was found to undergo ester alcolysis under the conditions of the
      carbonylation reaction.

PMID- 27711795
TI  - Statistical analysis of the photodegradation of imazethapyr on the surface of
      extracted soybean (Glycine max) and corn (Zea mays) epicuticular waxes.
AB  - The photodegradation rate of the herbicide imazethapyr on epicuticular waxes of
      soybean and corn plants was investigated. Plant age, relative humidity,
      temperature, and number of light banks were varied during plant growth, analyzed
      statistically, and examined to determine if these factors had an effect on the
      photodegradation of imazethapyr. Through ultraviolet/visible (UV-Vis) and
      fluorescence spectroscopy, epicuticular wax characteristics of soybean and corn
      plants were explored, were used to confirm observations determined statistically,
      and explain correlations between the rate constants and the composition of the
      epicuticular waxes. Plant age, the interaction between plant age and light, and
      the quadratic dependence on temperature were all determined to have a significant
      impact on the photodegradation rate of imazethapyr on the epicuticular waxes of
      soybean plants. As for the photodegradation rate on the epicuticular waxes of
      corn plants, the number of light banks used during growing and temperature were
      significant factors.

PMID- 27711796
TI  - Unimolecular dissociation of peptides: statistical vs. non-statistical
      fragmentation mechanisms and time scales.
AB  - In the present work we have investigated mechanisms of gas phase unimolecular
      dissociation of a relatively simple dipeptide, the di-proline anion, by means of
      chemical dynamics simulations, using the PM3 semi-empirical Hamiltonian. In
      particular, we have considered two activation processes that are representative
      limits of what occurs in collision induced dissociation experiments: (i) thermal
      activation, corresponding to several low energy collisions, in which the system
      is prepared with a microcanonical distribution of energy; (ii) collisional
      activation where a single shock of hundreds of kcal mol-1 (300 kcal mol-1 in the
      present case) can transfer sufficient energy to allow dissociation. From these
      two activation processes we obtained different product abundances, and for one
      particular fragmentation pathway a clear mechanistic difference for the two
      activation processes. This mechanism corresponds to the leaving of an OH- group
      and subsequent formation of water by taking a proton from the remaining molecule.
      This last reaction is always observed in thermal activation while in collisional
      activation it is less favoured and the formation of OH- as a final product is
      observed. More importantly, we show that while in thermal activation unimolecular
      dissociation follows exponential decay, in collision activation the initial
      population decays with non-exponential behaviour. Finally, from the thermal
      activation simulations it was possible to obtain rate constants as a function of
      temperature that show Arrhenius behaviour. Thus activation energies have also
      been extracted from these simulations.

PMID- 27711797
TI  - Retraction: Vibrational evidence for the "missing link" in structural kinship
      between kanemite and FSM-16 mesoporous silica.
AB  - Retraction of 'Vibrational evidence for the "missing link" in structural kinship
      between kanemite and FSM-16 mesoporous silica' by Ewa M. Serwicka, et al., Dalton
      Trans., 2016, DOI: 10.1039/C6DT01600F.

PMID- 27711798
TI  - Towards elucidating the photochemistry of the sunscreen filter ethyl ferulate
      using time-resolved gas-phase spectroscopy.
AB  - Ultrafast time-resolved ion yield (TR-IY) and velocity map imaging spectroscopies
      are employed to reveal the relaxation dynamics after photoexcitation in ethyl 4
      hydroxy-3-methoxycinnamate (ethyl ferulate, EF), an active ingredient in
      commercially available sunscreens. In keeping with a bottom-up strategy, the
      building blocks of EF, 2-methoxy-4-vinylphenol (MVP) and 4-hydroxy-3
      methoxycinnamyl alcohol (coniferyl alcohol, ConA), were also studied to assist in
      our understanding of the dynamics of EF as we build up in molecular complexity.
      In contrast to the excited state dynamics of MVP and ConA, which are described by
      a single time constant (>900 ps), the dynamics of EF are described by three time
      constants (15 +/- 4 ps, 148 +/- 47 ps, and >900 ps). A mechanism is proposed
      involving internal conversion (IC) between the initially excited S1(11pipi*) and
      S2(11npi*) states followed by intramolecular vibrational redistribution (IVR) on
      both states, in competition with intersystem crossing onto neighbouring triplet
      states (15 +/- 4 ps). IVR and IC within the triplet manifold then ensues (148 +/-
      47 ps) to populate a low-lying triplet state (>900 ps). Importantly, the
      fluorescence spectrum of EF at the S1 origin, along with the associated lifetime
      (6.9 +/- 0.1 ns), suggests that population is trapped, during initial IVR, on the
      S1(11pipi*) state. This serves to demonstrate the complex, competing dynamics in
      this sunscreen filter molecule.

PMID- 27711799
TI  - Bilayer structured supramolecular light harvesting arrays based on zinc porphyrin
      coordination polymers for enhanced photocurrent generation in dye sensitized
      solar cells.
AB  - An acylhydrazone zinc porphyrin P1 and its coordination polymers (CPs, denoted as
      P1M, M = Mn, Co, Ni, Cu, Zn) with different metal ions (Mn2+, Co2+, Ni2+, Cu2+
      and Zn2+) were synthesized. Then these coordination polymers were assembled into
      bilayer structured supramolecular chromophores through axially coordinating with
      anchoring porphyrin AP, and their performance in dye sensitized solar cells was
      investigated. Our results reveal that the bilayer structured supramolecular
      chromophore based solar cells show significantly improved photocurrent conversion
      efficiency. Particularly, P1Mn and P1Zn based solar cells showed a relatively
      higher short circuit current density (JSC) due to their broad absorption bands
      and remarkable light harvesting abilities. Meanwhile, the VOC values of the cells
      fabricated with the bilayered chromophores slightly decreased. Electrochemical
      impedance spectroscopy (EIS) in combination with charge extraction (CE) and
      transient photovoltage decay (TPD) measurements indicates that the decreased VOC
      resulted from the vigorous electron recombination and the downward shifted
      conduction band edge (ECB) of titania.

PMID- 27711800
TI  - Donor-substituted phosphanes - surprisingly weak Lewis donors for phosphenium
      cation stabilisation.
AB  - Paradoxically, N- and O-donor substituted tri-arylphosphanes are shown to be
      weaker donors than PPh3 when binding the soft Lewis acid moiety [PPh2]+. This
      arises from internal solvation and rehybridisation at phosphorus, precluding
      chelation and increasing steric demand, in direct contrast to coordination modes
      observed for metal complexes.

PMID- 27711801
TI  - Plasmon resonance energy transfer and hot electron injection induced high
      photocurrent density in liquid junction Ag@Ag2S sensitized solar cells.
AB  - An in situ technique was developed to deposit Ag@Ag2S core-shell quantum dots on
      a SnO2 mesoporous film for solar energy conversion. When adopted as a photoanode,
      an impressive high photocurrent density of ~25.6 mA cm-2 was demonstrated in a
      cell configuration using polysulfide S2-/Sn2- as an electrolyte and Cu2S/brass as
      a counter electrode, which leads to a power conversion efficiency of ~0.784% for
      this environmentally benign device. Optical measurements showed that Ag
      nanoparticles could be employed as plasmon resonance centers to enhance the
      harvesting efficiency of incident light at the visible and near-infrared range.
      Moreover, photoluminescence spectra demonstrated fast charge transfer at
      Ag@Ag2S/SnO2 interfaces, which facilitates direct hot electron injection from
      sensitizers to the SnO2 matrix and finally gives rise to the high photocurrent
      density.

PMID- 27711802
TI  - An organo-functionalized metal-oxide cluster, [VO6{(OCH2CH2)2N(CH2CH2OH)}6], with
      Anderson-like structure.
AB  - A new polyoxovanadium cluster compound, [VO6{(OCH2CH2)2N(CH2CH2OH)}6].0.5CH3CN,
      was synthesized and characterized by single-crystal X-ray diffraction analysis,
      FTIR and UV-vis spectroscopy, and TGA. The cluster is composed of a fully reduced
      cyclic {V6N6O18} framework, which adopts an Anderson-like structure and is
      comprised of a ring of six edge-sharing {VO5N} octahedra incorporating six
      {(OCH2CH2)2N(CH2CH2OH)} ligands. Two (OCH2CH2-) arms of each of the six
      triethanolamine ligands are directly incorporated into the oxometalate core and
      the third {-CH2CH2OH} arm remains pendant. In the condensed phase, the clusters
      form discrete hcp layers through inter-cluster hydrogen bonding. These layers
      stack through soft chemical interactions to form a 3D network structure. The
      neutral cluster, [VO6{(OCH2CH2)2N(CH2CH2OH)}6], is the isopolyoxovanadium
      analogue to the cationic clusters contained in a series of heteropolyoxovanadium
      compounds previously introduced by our laboratory, e.g.,
      [LiVO6{(OCH2CH2)2N(CH2CH2OH)}6]+; its existence shows that a heteroatom is not
      required to form or stabilize the common organofunctionalized vanadium oxide
      framework: [VO6{(OCH2CH2)2N(CH2CH2OH)}6]. To the best of our knowledge, the
      isopolyoxovanadium and heteropolyoxovanadium clusters represent the first
      reported isopoly-heteropoly analogues in the polyoxometalate field. We compare
      the TGA profile, FTIR and UV-vis spectra of the new compound with two of its
      cationic heteropoly analogues.

PMID- 27711804
TI  - Electrocatalytic reduction of carbon dioxide with Mn(terpyridine) carbonyl
      complexes.
AB  - The behavior of a series of Manganese (Mn) carbonyl compounds with 2,2':6',2''
      terpyridine (tpy) in kappa2-N,N' and kappa3-N,N',N'' coordination modes under
      electrochemically reducing conditions is reported. In the presence of carbon
      dioxide (CO2) and Bronsted acid (phenol), two-electron reduction to carbon
      monoxide (CO) and water (H2O) is observed. Based on data obtained from cyclic
      voltammetry and infrared spectroelectrochemistry, the active state of the
      catalyst in the proposed mechanism for all cases is [Mn(kappa3-N,N',N''
      tpy)(CO)2]-. Under these conditions, competing decomposition reactions limit the
      overall Faradaic efficiency. These results suggest the possibility of developing
      new tridentate ligand frameworks suitable for catalytic systems with Mn carbonyl
      cores.

PMID- 27711805
TI  - The structure of a one-electron oxidized Mn(iii)-bis(phenolate)dipyrrin radical
      complex and oxidation catalysis control via ligand-centered redox activity.
AB  - The tetradentate ligand dppH3, which features a half-porphyrin and two electron
      rich phenol moieties, was prepared and chelated to manganese. The mononuclear
      Mn(iii)-dipyrrophenolate complex 1 was structurally characterized. The metal ion
      lies in a square pyramidal environment, the apical position being occupied by a
      methanol molecule. Complex 1 displays two reversible oxidation waves at 0.00 V
      and 0.47 V vs. Fc+/Fc, which are assigned to ligand-centered processes. The one
      electron oxidized species 1+ SbF6- was crystallized, showing an octahedral
      Mn(iii) center with two water molecules coordinated at both apical positions. The
      bond distance analysis and DFT calculations disclose that the radical is
      delocalized over the whole aromatic framework. Complex 1+ SbF6- exhibits an Stot
      = 3/2 spin state due to the antiferromagnetic coupling between Mn(iii) and the
      ligand radical. The zero field splitting parameters are D = 1.6 cm-1, E/D =
      0.18(1), g? = 1.99 and g? = 1.98. The dication 12+ is an integer spin system,
      which is assigned to a doubly oxidized ligand coordinated to a Mn(iii) metal
      center. Both 1 and 1+ SbF6- catalyze styrene oxidation in the presence of PhIO,
      but the nature of the main reaction product is different. Styrene oxide is the
      main reaction product when using 1, but phenylacetaldehyde is formed
      predominantly when using 1+ SbF6-. We examined the ability of complex 1+ SbF6- to
      catalyze the isomerization of styrene oxide and found that it is an efficient
      catalyst for the anti-Markovnikov opening of styrene oxide. The formation of
      phenylacetaldehyde from styrene therefore proceeds in a tandem E-I (epoxidation
      isomerization) mechanism in the case of 1+ SbF6-. This is the first evidence of
      control of the reactivity for styrene oxidation by changing the oxidation state
      of a catalyst based on a redox-active ligand.

PMID- 27711803
TI  - Towards characterization of photo-excited electron transfer and catalysis in
      natural and artificial systems using XFELs.
AB  - The ultra-bright femtosecond X-ray pulses provided by X-ray Free Electron Lasers
      (XFELs) open capabilities for studying the structure and dynamics of a wide
      variety of biological and inorganic systems beyond what is possible at
      synchrotron sources. Although the structure and chemistry at the catalytic sites
      have been studied intensively in both biological and inorganic systems, a full
      understanding of the atomic-scale chemistry requires new approaches beyond the
      steady state X-ray crystallography and X-ray spectroscopy at cryogenic
      temperatures. Following the dynamic changes in the geometric and electronic
      structure at ambient conditions, while overcoming X-ray damage to the redox
      active catalytic center, is key for deriving reaction mechanisms. Such studies
      become possible by using the intense and ultra-short femtosecond X-ray pulses
      from an XFEL, where sample is probed before it is damaged. We have developed
      methodology for simultaneously collecting X-ray diffraction data and X-ray
      emission spectra, using an energy dispersive spectrometer, at ambient conditions,
      and used this approach to study the room temperature structure and intermediate
      states of the photosynthetic water oxidizing metallo-protein, photosystem II.
      Moreover, we have also used this setup to simultaneously collect the X-ray
      emission spectra from multiple metals to follow the ultrafast dynamics of light
      induced charge transfer between multiple metal sites. A Mn-Ti containing system
      was studied at an XFEL to demonstrate the efficacy and potential of this method.

PMID- 27711806
TI  - Synthesis and reactivity of N,N'-1,4-diazabutadiene derived borocations.
AB  - A series of borocations have been synthesised from the addition of haloboranes to
      synthetically accessible N,N'-1,4-diazabutadiene precursors, which are derived
      from commercially available anilines. The synthesis and structural studies of the
      borocations are described.

PMID- 27711807
TI  - Reactions facilitated by ligand design.

PMID- 27711808
TI  - Toward fully quantum modelling of ultrafast photodissociation imaging
      experiments. Treating tunnelling in the ab initio multiple cloning approach.
AB  - We present an account of our recent effort to improve simulation of the
      photodissociation of small heteroaromatic molecules using the Ab Initio Multiple
      Cloning (AIMC) algorithm. The ultimate goal is to create a quantitative and
      converged technique for fully quantum simulations which treats both electrons and
      nuclei on a fully quantum level. We calculate and analyse the total kinetic
      energy release (TKER) spectra and Velocity Map Images (VMI), and compare the
      results directly with experimental measurements. In this work, we perform new
      extensive calculations using an improved AIMC algorithm that now takes into
      account the tunnelling of hydrogen atoms. This can play an extremely important
      role in photodissociation dynamics.

PMID- 27711809
TI  - In situ video-STM studies of the mechanisms and dynamics of electrochemical
      bismuth nanostructure formation on Au.
AB  - The microscopic mechanisms of Bi electrodeposition on Au(111) and Au(100)
      electrodes in the overpotential regime were studied by in situ scanning tunneling
      microscopy with high spatial and temporal resolution. Atomic resolution images of
      the needle-like Bi(110) deposits formed on Au(111) reveal the central influence
      of covalent Bi-Bi bonds on the deposit morphology. In the straight steps along
      the needle edges the Bi atoms are interlinked by these bonds, whereas at the
      needle tip and at kinks along the needle edges dangling bonds exist, explaining
      the rapid structural fluctuations at these sites. For ultrathin Bi deposits on
      Au(100) a more open atomic arrangement was found within the surface plane, which
      was tentatively assigned to an epitaxially stabilised Bi(111) film. Furthermore,
      well-defined nanowires, consisting of zigzag chains of Bi surface atoms, were
      observed on this surface.

PMID- 27711810
TI  - Activation of aldehydes by exocyclic iridium(i)-eta4:pi2-diene complexes derived
      from 1,3-oxazolidin-2-ones.
AB  - The Ir(i) complexes [TpMe2Ir(eta4-1,4-diene)] 2b and 2c react thermally with a
      variety of aromatic aldehydes, 3a-e, to generate the metallabicyclic compounds 4e
      k and the Fischer-type carbenes 5a-b in moderate yields. These reactions are
      proposed to take place with the initial formation of eta1-aldehyde adducts as key
      intermediates. The formation of the metallabicyclic compounds 4e-k involves a
      formal decarboxylation process at the exo-2-oxazolidinone diene and an ortho
      metallation of the aromatic ring. The generation of the Fischer-type carbenes 5a
      b is the result of a series of metal-based rearranged intermediates with no
      decarboxylation observed. Treatment of the eta4-diene complex 2b with a variety
      of Lewis bases induces a change in the binding mode of the diene ligand from
      eta4:pi2 to eta2:sigma2 to form the Ir(iii) derivatives 6b-d of composition
      TpMe2Ir-(eta4:pi2-1,4-diene)(L) (L = CO, MeCN, and C5H5N). A study of reactions
      of complex 2b with either mono- or poly-deuterated aldehydes was performed to
      understand the mechanisms of such processes. The results of these studies were
      used to determine plausible formation mechanisms of the metallabicyclic compounds
      4e-4k and Fischer-type carbenes 5a-b compound series. These mechanisms were
      corroborated by density functional theory (DFT) calculations of the free energy
      profiles.

PMID- 27711811
TI  - S-shooting: a Bennett-Chandler-like method for the computation of rate constants
      from committor trajectories.
AB  - Mechanisms of rare transitions between long-lived stable states are often
      analyzed in terms of commitment probabilities, determined from swarms of short
      molecular dynamics trajectories. Here, we present a computer simulation method to
      determine rate constants from such short trajectories combined with free energy
      calculations. The method, akin to the Bennett-Chandler approach for the
      calculation of reaction rate constants, requires the definition of a valid
      reaction coordinate and can be applied to both under- and overdamped dynamics. We
      verify the correctness of the algorithm using a one-dimensional random walker in
      a double-well potential and demonstrate its applicability to complex transitions
      in condensed systems by calculating cavitation rates for water at negative
      pressures.

PMID- 27711812
TI  - Decoherence, control and attosecond probing of XUV-induced charge migration in
      biomolecules. A theoretical outlook.
AB  - The sudden ionization of a molecule by an attosecond pulse is followed by charge
      redistribution on a time scale from a few femtoseconds down to hundreds of
      attoseconds. This ultrafast redistribution is the result of the coherent
      superposition of electronic continua associated with the ionization thresholds
      that are reached by the broadband attosecond pulse. Thus, a correct theoretical
      description of the time evolution of the ensuing wave packet requires the
      knowledge of the actual ionization amplitudes associated with all open ionization
      channels, a real challenge for large and medium-size molecules. Recently, the
      first calculation of this kind has come to light, allowing for interpretation of
      ultrafast electron dynamics observed in attosecond pump-probe experiments
      performed on the amino acid phenylalanine [Calegari et al., Science 2014, 346,
      336]. However, as in most previous theoretical works, the interpretation was
      based on various simplifying assumptions, namely, the ionized electron was not
      included in the description of the cation dynamics, the nuclei were fixed at
      their initial position during the hole migration process, and the effect of the
      IR probe pulse was ignored. Here we go a step further and discuss the
      consequences of including these effects in the photoionization of the glycine
      molecule. We show that (i) the ionized electron does not affect hole dynamics
      beyond the first femtosecond, and (ii) nuclear dynamics has only a significant
      effect after approximately 8 fs, but does not destroy the coherent motion of the
      electronic wave packet during at least few additional tens of fs. As a first step
      towards understanding the role of the probe pulse, we have considered an XUV
      probe pulse, instead of a strong IR one, and show that such an XUV probe does not
      introduce significant distortions in the pump-induced dynamics, suggesting that
      pump-probe strategies are suitable for imaging and manipulating charge migration
      in complex molecules. Furthermore, we show that hole dynamics can be changed by
      shaping the attosecond pump pulse, thus opening the door to the control of charge
      dynamics in biomolecules.

PMID- 27711814
TI  - Theory of electrostatic phenomena in water-filled Pt nanopores.
AB  - The emerging field of nanoprotonics is concerned with controlling proton
      distribution and transport in nanoporous media. These phenomena, dictated by the
      surface charging properties of the host medium, are of vital importance in porous
      electrodes for fuel cells, electrolysers, supercapacitors and nanofluidic
      devices. In this theoretical study, we explore the interplay of the metal
      charging relation with the proton density and oxygen reduction activity in a
      water-filled nanopore with walls made of platinum. We exploit a non-monotonic
      charging behavior derived from a refined structural model of the Pt-solution
      interface. This charging relation replaces the oversimplified linear relation
      that has been widely used in practical applications. The water-filled pore, with
      one opening interfacing with a polymer electrolyte membrane as a proton source,
      always possesses negative surface charge in the potential range of 0-1.0 V (RHE).
      Therefore, its proton conductivity can be several orders higher than that of pure
      water. We obtain an analytical expression for the oxygen reduction activity of
      the nanopore and parameterize it using the polarization data of an ionomer-free
      thin-film Pt electrode. The structure vs. performance relation of the water
      filled Pt nanopore is examined.

PMID- 27711813
TI  - Novel dinitromethyl-featured polynitro energetic salts.
AB  - A unique and facile method was developed to synthesize a new class of energetic
      salts based on 2-amino-1,1,5,5-tetranitro-4-oxo-3-aza-pentene. All the salts were
      fully characterized by NMR (1H and 13C), IR spectroscopy and elemental analysis.
      Furthermore, the crystal structure of the guanidinium salt (5) was determined by
      single-crystal X-ray diffraction. The differential scanning calorimetry (DSC)
      results showed that the decomposition temperatures of these salts were between
      126.2  degrees C (10) and 148.8  degrees C (9). The densities of these salts lie
      in the range of 1.745 (8) to 1.880 (4) g cm-3. Their impact sensitivities and
      friction sensitivities were measured to be in the range of 1-16 J and 48-84 N,
      respectively. All the salts exhibited promising detonation performances
      (detonation pressure: 28.6 to 34.3 GPa; detonation velocity: 8037 to 8674 m s-1),
      and the detonation performances of salt 4 were comparable to those of RDX.

PMID- 27711815
TI  - The effects of substituent position on kinetics of benzene vapour adsorption onto
      3-phenylphenoxy substituted metal-free and metallo-phthalocyanines thin films.
AB  - The preparation of metal-free, Zn(ii), In(iii), and Cu(ii)-phthalocyanines
      containing tetrakis-(3-phenylphenoxy) groups was achieved by employing 3-(3
      phenylphenoxy)phthalonitrile (1) and 4-(3-phenylphenoxy)phthalonitrile (2) as
      starting materials. The phthalonitriles and phthalocyanines were characterized by
      elemental analysis, infrared, proton nuclear magnetic resonance, ultraviolet
      visible, and matrix-assisted laser desorption/ionization time-of-flight mass
      spectroscopic techniques. The effect of the substituent group on the kinetics of
      benzene vapour adsorption onto these novel compounds was examined using three
      kinetics models: the pseudo first-order model, the Elovich equation, and a simple
      adsorption-desorption model. Results show that the benzene adsorption kinetics
      strongly depend on the position of the substituent groups.

PMID- 27711816
TI  - A theoretical consideration of ion size effects on the electric double layer and
      voltammetry of nanometer-sized disk electrodes.
AB  - Considering that an electric-double-layer (EDL) structure may significantly
      impact on the mass transport and charge transfer kinetics at the interfaces of
      nanometer-sized electrodes, while EDL structures could be altered by the finite
      sizes of electrolyte and redox ions, the possible effects of ion sizes on EDL
      structures and voltammetric responses of nanometer-sized disk (nanodisk)
      electrodes are investigated. Modified Boltzmann and Nernst-Planck (NP) equations,
      which include the influence of the finite ion volumes, are combined with the
      Poisson equation and modified Butler-Volmer equation to gain knowledge on how the
      finite sizes of ions and the nanometer sizes of electrodes may couple with each
      other to affect the structures and reactivities of a nanoscale electrochemical
      interface. Two typical ion radii, 0.38 nm and 0.68 nm, which could represent the
      sizes of the commonly used aqueous electrolyte ions (e.g., the solvated K+) and
      the organic electrolyte ions (e.g., the solvated TEA+) respectively, are
      considered. The finite size of ions can result in decreased screening of
      electrode charges, therefore magnifying EDL effects on the ion transport and the
      electron transfer at electrochemical interfaces. This finite size effect of ions
      becomes more pronounced for larger ions and at smaller electrodes as the
      electrode radii is larger than 10 nm. For electrodes with radii smaller than 10
      nm, however, the ion size effect may be less pronounced with decreasing the
      electrode size. This can be explained in terms of the increased edge effect of
      disk electrodes at nanometer scales, which could relax the ion crowding at/near
      the outer Helmholtz plane. The conditions and situations under which the ion
      sizes may have a significant effect on the voltammetry of electrodes are
      discussed.

PMID- 27711817
TI  - Beyond structure: ultrafast X-ray absorption spectroscopy as a probe of non
      adiabatic wavepacket dynamics.
AB  - The excited state non-adiabatic dynamics of polyatomic molecules, leading to the
      coupling of structural and electronic dynamics, is a fundamentally important yet
      challenging problem for both experiment and theory. Ongoing developments in
      ultrafast extreme vacuum ultraviolet (XUV) and soft X-ray sources present new
      probes of coupled electronic-structural dynamics because of their novel and
      desirable characteristics. As one example, inner-shell spectroscopy offers
      localized, atom-specific probes of evolving electronic structure and bonding (via
      chemical shifts). In this work, we present the first on-the-fly ultrafast X-ray
      time-resolved absorption spectrum simulations of excited state wavepacket
      dynamics: photo-excited ethylene. This was achieved by coupling the ab initio
      multiple spawning (AIMS) method, employing on-the-fly dynamics simulations, with
      high-level algebraic diagrammatic construction (ADC) X-ray absorption cross
      section calculations. Using the excited state dynamics of ethylene as a test
      case, we assessed the ability of X-ray absorption spectroscopy to project out the
      electronic character of complex wavepacket dynamics, and evaluated the
      sensitivity of the calculated spectra to large amplitude nuclear motion. In
      particular, we demonstrate the pronounced sensitivity of the pre-edge region of
      the X-ray absorption spectrum to the electronic and structural evolution of the
      excited-state wavepacket. We conclude that ultrafast time-resolved X-ray
      absorption spectroscopy may become a powerful tool in the interrogation of
      excited state non-adiabatic molecular dynamics.

PMID- 27711818
TI  - Faraday efficiency and mechanism of electrochemical surface reactions: CO2
      reduction and H2 formation on Pt(111).
AB  - An atomic scale model of the electrical double layer is used to calculate the
      mechanism and rate of electrochemical reduction of CO2 as well as H2 formation at
      a Pt(111) electrode. The water layer contains solvated protons and the electrode
      has excess electrons at the surface. Density functional theory within the
      generalized gradient approximation is used to describe the electronic structure
      while the mechanism and activation energy of the various elementary reactions is
      obtained by calculating minimum energy paths using the nudged elastic band
      method. The applied electrical potential is deduced from the calculated work
      function. The optimal reaction mechanism for CO2 reduction to either methane or
      methanol is found and the estimated rate compared with that of the competing
      reaction, H2 formation. When the free energy of only the intermediates and
      reactants is taken into account, not the activation energy, Pt(111) would seem to
      be a good electrocatalyst for CO2 reduction, significantly better than Cu(111).
      This, however, contradicts experimental findings. Detailed calculations reported
      here show that the activation energy for CO2 reduction is high for both Heyrovsky
      and Tafel mechanisms on Pt(111) in the relevant range of applied potential. The
      rate-limiting step of the Heyrovsky mechanism, *COOH + H+ + e- -> *CO + H2O, is
      estimated to have an activation energy of 0.95 eV at -0.9 V vs. standard hydrogen
      electrode. Under the same conditions, the activation energy for H2 formation is
      estimated to be only 0.5 eV. This explains why attempts to reduce CO2 using
      platinum electrodes have produced only H2. A comparison is made with analogous
      results for Cu(111) [J. Hussain et al., Procedia Comput. Sci., 2015, 51, 1865]
      where a reaction mechanism with low activation energy for CO2 electroreduction to
      methane was identified. The difference between the two electrocatalysts is
      discussed.

PMID- 27711819
TI  - Construction of copper chains with new fluorescent guanidino-functionalized
      naphthyridine ligands.
AB  - The three new blue-fluorescent ligands 2,7-bis(tetramethylguanidino)-1,8
      naphthyridine (1), 2,7-bis(N,N'-dimethylethylene-guanidino)-1,8-naphthyridine (2)
      and 2,7-bis(N,N'-diisopropylguanidino)-1,8-naphthyridine (3) are synthesized, and
      their optical properties (electronic absorption and emission spectroscopy)
      studied. Reactions of 1 or 2 with [Cu(CH3CN)4]BF4 yield the Cu4 chain compounds
      [Cu4(1)2](BF4)4 (that crystallizes as [Cu4(1)2(CH3CN)2](BF4)4.2CH2Cl2) and
      [Cu4(2)2](BF4)4. The variations of the optical properties upon coordination are
      evaluated, and the electronic transitions identified by time-dependent DFT (TD
      DFT) calculations. Then the redox properties of the new Cu4 chain complexes are
      studied. In the course of these experiments, the new Cu6 complex
      [Cu4(1)2(CuCl2)2]2+, in which two CuCl2- units coordinate to the Cu4 chain in
      [Cu4(1)2]4+, was fully characterized. In addition, the Cu3 chain complexes
      [Cu3(1)3]3+ and [Cu3(1)2]3+ were isolated as products of redox-induced
      degradation processes. Finally, we show by quantum chemical calculations that in
      [M4(1)2]4+ complexes (M = coinage metal), the HOMO changes from a ligand-centered
      to a metal-centered orbital for replacement of M = Cu by Au.

PMID- 27711820
TI  - Interactions of anions and cations in carbon nanotubes.
AB  - We consider the insertion of alkali-halide ion pairs into a narrow (5,5) carbon
      nanotube. In all cases considered, the insertion of a dimer is only slightly
      exothermic. While the image charge induced on the surface of the tube favors
      insertion, it simultaneously weakens the Coulomb attraction between the two ions.
      In addition, the anion experiences a sizable Pauli repulsion. For a one
      dimensional chain of NaCl embedded in the tube the most favorable position for
      the anion is at the center, and for the cation near the wall. The phonon spectrum
      of such chains shows both an acoustic and an optical branch.

PMID- 27711821
TI  - The antioxidant effect of mulberry and jamun fruit wines by ameliorating
      oxidative stress in streptozotocin-induced diabetic Wistar rats.
AB  - Polyphenols act by scavenging reactive oxygen species during oxidative stress and
      hence are useful in the treatment of metabolic disorders including diabetes. This
      study describes the effect of polyphenol rich mulberry and jamun wines fed to
      streptozotocin-induced diabetic rats. To male adult Wistar rats, divided into
      groups (n = 10 per group) intraperitoneal injection was administered with
      streptozotocin at 38 mg per kg body weight for inducing diabetes. After
      confirmation of diabetes, rats divided into groups were fed each day with 5.7
      milliliter per kg body weight of mulberry, jamun, white and red grape wines for 6
      weeks. One group of animals received resveratrol at 20 mg per kg body weight.
      After six weeks of treatment, blood glucose, urinary profile, lipid profile,
      plasma, liver, kidney, brain and eye antioxidant enzyme activities, lipid
      peroxidation, non-esterified fatty acids (NEFA) and hepatic glutathione (GSH)
      content were determined. Though wine and resveratrol feeding did not improve the
      glycemic status of diabetic rats, increases in antioxidant enzymes and GSH
      content accompanied by reduced NEFA and lipid peroxidation were observed. The
      kidneys and brains of resveratrol fed rats showed significant reduction in
      malondialdehyde equivalents, exhibited an improved antioxidant status of tissues
      and an increased glutathione content. The findings suggested that the wines can
      ameliorate the consequences of diabetes due to their antioxidants.

PMID- 27711822
TI  - Controllable fabrication of urchin-like Co3O4 hollow spheres for high-performance
      supercapacitors and lithium-ion batteries.
AB  - Urchin-like cobalt oxide (Co3O4) hollow spheres can be successfully prepared by
      thermal decomposition of cobalt carbonate hydroxide hydrate
      (Co(CO3)0.5(OH).0.11H2O) obtained by template-assisted hydrothermal synthesis.
      The morphology, crystal structure evolution and thermal decomposition behaviors
      of the as-prepared products have been carefully investigated. A plausible
      formation mechanism of the urchin-like Co3O4 hollow spheres in the presence of
      hexadecyl trimethyl ammonium bromide (CTAB) as the surfactant template is
      proposed. The urchin-like Co3O4 hollow spheres are further constructed as
      electrode materials for high-performance supercapacitors with a high specific
      capacitance of 460 F g-1 at a current density of 4 A g-1 and excellent cycling
      stability. Furthermore, as anode materials for lithium-ion batteries (LIBs),
      superior lithium storage performance of 1342.2 mA h g-1 (0.1 C) and 1122.7 mA h g
      1 (0.2 C) can also be achieved. The excellent performances can be ascribed to the
      unique hierarchical urchin-like hollow structure of the electrode materials,
      which offers a large specific surface area, short electron and ion diffusion
      paths and high permeability while being directly in contact with the electrolyte.
      Moreover, the hollow structure with sufficient internal void spaces can self
      accommodate volume change during electrochemical reactions, which improves the
      structural stability and integrity.

PMID- 27711823
TI  - Ligand-dependent formation of ion-pair CuI/CuIII trifluoromethyl complexes
      containing bisphosphines.
AB  - We report novel ion-pair bisphosphine CuI/CuIII trifluoromethyl complexes
      [(P2)2CuI]+[CuIII(CF3)4]- (P2 = DPPE, BINAP or Xantphos) featuring tetrahedral
      CuI and square planar CuIII units that are prepared via oxidative
      trifluoromethylation of CuI with CF3SiMe3 in the presence of AgF. The
      bisphosphine CuI/CuIII CF3 complexes are highly reactive for aerobic
      trifluoromethylation of arylboronic acids to produce trifluoromethylated arenes
      in good to quantitative yields, which is in sharp contrast to the CuI/CuIII
      complex with phen/PPh3 ligands (1'). These results not only provide strong
      evidence that both the neutral and ion-pair CuIII CF3 complexes are competent
      catalytic species for Cu-mediated oxidative trifluoromethylation reactions, but
      also have important mechanistic implications that the active catalyst and
      reaction mechanism should be distinct and ligand-dependent for
      trifluoromethylation reactions with different types of ancillary ligands.

PMID- 27711825
TI  - "CLICKable" azide-functionalized phosphonates for the surface-modification of
      molecular and solid-state metal oxides.
AB  - The covalent functionalization of metal oxide surfaces with organic ligands gives
      unique organic-inorganic hybrids. Here we report a bifunctional organic tether
      combining a phosphonate for metal oxide anchoring with an organic azide for
      attachment of organic groups. Stable binding of the tether to molecular and solid
      state metal oxides is demonstrated and the subsequent "CLICKability" of the TiO2
      anchored tether is shown. The phosphonate-azide reported could in future allow
      the general linkage of functional organic groups to metal oxides.

PMID- 27711824
TI  - The effect of a plant extract enriched in stigmasterol and beta-sitosterol on
      glycaemic status and glucose metabolism in alloxan-induced diabetic rats.
AB  - Banana is an extensively cultivated plant worldwide, mainly for its fruit, while
      its ancillary product, the banana pseudostem, is consumed as a vegetable and is
      highly recommended for diabetics in the traditional Indian medicine system. The
      present study was aimed at elucidating the mechanism of antihyperglycaemia
      exerted by the ethanol extract of banana pseudostem (EE) and its isolated
      compounds viz., stigmasterol (C1) and beta-sitosterol (C2), in an alloxan-induced
      diabetic rat model. Diabetic rats which were administered with C1, C2 and EE (100
      and 200 mg per kg b. wt.) for 4 weeks showed reduced levels of fasting blood
      glucose and reversal of abnormalities in serum/urine protein, urea and creatinine
      in diabetic rats compared to the diabetic control group of rats. Diabetic
      symptoms such as polyphagia, polydipsia, polyuria, urine glucose and reduced body
      weight were ameliorated in the diabetic group of rats fed with EE, C1 and C2 (100
      mg per kg b. wt., once daily) for 28 days. The levels of insulin and Hb were also
      increased, while the HbA1c level was reduced. The altered activities of hepatic
      marker enzymes viz., aspartate transaminase (AST), alanine transaminase (ALT) and
      alkaline phosphatase (ALP); glycolytic enzyme (hexokinase); shunt enzyme (glucose
      6-phosphate dehydrogenase); gluconeogenic enzymes (glucose-6-phosphatase,
      fructose-1,6-bisphosphatase and lactate dehydrogenase) and pyruvate kinase were
      significantly reverted to normal levels by the administration of EE, C1 and C2.
      In addition, increased levels of hepatic glycogen and glycogen synthase and the
      corresponding decrease of glycogen phosphorylase activity in diabetic rats
      illustrated the antihyperglycaemic potential of EE and its components. The
      histological observations revealed a marked regeneration of the beta-cells in the
      drug treated diabetic rats. These findings suggest that EE might exert its
      antidiabetic potential in the presence of C1 and C2, attributable to the enhanced
      glycolytic activity, besides increasing the hepatic glucose utilization in
      diabetic rats by stimulating insulin secretion from the remnant beta-cells.

PMID- 27711826
TI  - Femtosecond gas phase electron diffraction with MeV electrons.
AB  - We present results on ultrafast gas electron diffraction (UGED) experiments with
      femtosecond resolution using the MeV electron gun at SLAC National Accelerator
      Laboratory. UGED is a promising method to investigate molecular dynamics in the
      gas phase because electron pulses can probe the structure with a high spatial
      resolution. Until recently, however, it was not possible for UGED to reach the
      relevant timescale for the motion of the nuclei during a molecular reaction.
      Using MeV electron pulses has allowed us to overcome the main challenges in
      reaching femtosecond resolution, namely delivering short electron pulses on a gas
      target, overcoming the effect of velocity mismatch between pump laser pulses and
      the probe electron pulses, and maintaining a low timing jitter. At electron
      kinetic energies above 3 MeV, the velocity mismatch between laser and electron
      pulses becomes negligible. The relativistic electrons are also less susceptible
      to temporal broadening due to the Coulomb force. One of the challenges of
      diffraction with relativistic electrons is that the small de Broglie wavelength
      results in very small diffraction angles. In this paper we describe the new setup
      and its characterization, including capturing static diffraction patterns of
      molecules in the gas phase, finding time-zero with sub-picosecond accuracy and
      first time-resolved diffraction experiments. The new device can achieve a
      temporal resolution of 100 fs root-mean-square, and sub-angstrom spatial
      resolution. The collimation of the beam is sufficient to measure the diffraction
      pattern, and the transverse coherence is on the order of 2 nm. Currently, the
      temporal resolution is limited both by the pulse duration of the electron pulse
      on target and by the timing jitter, while the spatial resolution is limited by
      the average electron beam current and the signal-to-noise ratio of the detection
      system. We also discuss plans for improving both the temporal resolution and the
      spatial resolution.

PMID- 27711827
TI  - 1/f 2 noise in bistable electrocatalytic reactions on mesoscale electrodes.
AB  - The formation of a self-organized spatial domain during current-controlled CO
      oxidation, a kinetically bistable reaction, is investigated experimentally and by
      deterministic simulations as a function of the electrode size and of the
      supporting electrolyte concentration. Decreasing the microelectrode size leads to
      the suppression of the spatial instability at the electrode and thus stabilizes
      the S-NDR branch of the reaction. The critical microelectrode size capable of
      supporting sustained domain formation is shown to be strongly affected by the
      sulfuric acid concentration, the characteristic time of the positive feedback
      loop increasing with the sulfate concentration. Furthermore, we demonstrate that
      for microelectrode diameters close to the instability threshold, small amplitude
      electrochemical potential fluctuations appear in the system. These potential
      fluctuations cannot be captured by deterministic mathematical models and are
      attributed to a strong enhancement of molecular fluctuations or intrinsic noise
      in the vicinity of the spatial instability. Analysis of the electrochemical noise
      revealed a 1/f 2 frequency dependence and several common features with neuronal
      shot noise.

PMID- 27711828
TI  - A comparison of MOP-phosphonite ligands and their applications in Rh(i)- and
      Pd(ii)-catalysed asymmetric transformations.
AB  - Six chiral MOP-phosphonites have been synthesised and compared via experimental
      and computational methods in an effort to quantify their differing structural and
      electronic profiles. They were found to be electron-poor ligands in comparison to
      their arylphosphine analogues and have a larger trans influence in square planar
      Pt(ii) complexes. Four [Rh(LP)(eta2:eta2-cod)Cl] complexes were synthesised and
      characterised by NMR, HRMS and X-ray crystallography. Two [Rh(LP)2]BF4 complexes
      were prepared where one ligand acts as a chelating P,C-pi-donor; detailed NMR
      studies demonstrated a hemilabile eta6-coordination mode, which in one case was
      confirmed by X-ray crystallography. Rh(i) complexes were used as catalysts in
      asymmetric hydrogenation and hydroformylation reactions and in the addition of
      phenyl boronic acid to an isatin. Pd(ii) complexes were successfully employed in
      asymmetric Suzuki-Miyaura cross-coupling reactions yielding binaphthyl products.
      Two [Pd(LP)2Cl2] complexes were synthesised and characterised by X-ray
      crystallography, both adopting cis orientations, with one of the complexes
      crystallising as two pseudo-polymorphs.

PMID- 27711829
TI  - Probing spin-vibronic dynamics using femtosecond X-ray spectroscopy.
AB  - Ultrafast pump-probe spectroscopy within the X-ray regime is now possible owing
      to the development of X-ray Free Electrons Lasers (X-FELs) and is opening new
      opportunities for the direct probing of femtosecond evolution of the nuclei, the
      electronic and spin degrees of freedom. In this contribution we use wavepacket
      dynamics of the photoexcited decay of a new Fe(ii) complex, [Fe(bmip)2]2+ (bmip =
      2,6-bis(3-methyl-imidazole-1-ylidine)pyridine), to simulate the experimental
      observables associated with femtosecond Fe K-edge X-ray Absorption Near-Edge
      Structure (XANES) and X-ray emission (XES) spectroscopy. We show how the
      evolution of the nuclear wavepacket is translated into the spectroscopic signal
      and the sensitivity of these approaches for following excited state dynamics.

PMID- 27711830
TI  - Role of tunnel ionization in high harmonic generation from substituted benzenes.
AB  - We theoretically study high-harmonic generation in toluene, ortho-xylene and
      fluorobenzene driven by a 1.8 MUm ultrashort pulse. We find that the chemical
      substitutions have a strong influence on the amplitude and phase of the emission
      from the highest occupied molecular orbital, despite having a small influence on
      the orbital itself. We show that this influence is due to the tunnel ionization
      step, which depends critically on the sign and amplitude of the asymptotic part
      of the wave function. We discuss how these effects would manifest in phase
      sensitive high-harmonic generation spectroscopy experiments.

PMID- 27711831
TI  - Four-wave-mixing experiments with seeded free electron lasers.
AB  - The development of free electron laser (FEL) sources has provided an
      unprecedented bridge between the scientific communities working with ultrafast
      lasers and extreme ultraviolet (XUV) and X-ray radiation. Indeed, in recent years
      an increasing number of FEL-based applications have exploited methods and
      concepts typical of advanced optical approaches. In this context, we recently
      used a seeded FEL to demonstrate a four-wave-mixing (FWM) process stimulated by
      coherent XUV radiation, namely the XUV transient grating (X-TG). We hereby report
      on X-TG measurements carried out on a sample of silicon nitride (Si3N4). The
      recorded data bears evidence for two distinct signal decay mechanisms: one
      occurring on a sub-ps timescale and one following slower dynamics extending
      throughout and beyond the probed timescale range (100 ps). The latter is
      compatible with a slower relaxation (time decay > ns), that may be interpreted as
      the signature of thermal diffusion modes. From the peak intensity of the X-TG
      signal we could estimate a value of the effective third-order susceptibility
      which is substantially larger than that found in SiO2, so far the only sample
      with available X-TG data. Furthermore, the intensity of the time-coincidence peak
      shows a linear dependence on the intensity of the three input beams, indicating
      that the measurements were performed in the weak field regime. However, the
      timescale of the ultrafast relaxation exhibits a dependence on the intensity of
      the XUV radiation. We interpreted the observed behaviour as the generation of a
      population grating of free-electrons and holes that, on the sub-ps timescale,
      relaxes to generate lattice excitations. The background free detection inherent
      to the X-TG approach allowed the determination of FEL-induced electron dynamics
      with a sensitivity largely exceeding that of transient reflectivity and
      transmissivity measurements, usually employed for this purpose.

PMID- 27711832
TI  - Transformation of chlorpyrifos and chlorpyrifos-methyl in prairie pothole pore
      waters.
AB  - Non-point source pesticide pollution is a concern for wetlands in the prairie
      pothole region (PPR). Recent studies have demonstrated that reduced sulfur
      species (e.g., bisulfide and polysulfides) in PPR wetland pore waters directly
      undergo reactions with chloroacetanilide and dinitroaniline compounds. In this
      paper, the abiotic transformation of two organophosphate compounds, chlorpyrifos
      and chlorpyrifos-methyl, was studied in PPR wetland pore waters. Chlorpyrifos
      methyl reacted significantly faster (up to 4 times) in pore water with reduced
      sulfur species relative to hydrolysis. No rate enhancement was observed in the
      transformation of chlorpyrifos in pore water with reduced sulfur species. The
      lack of reactivity was most likely caused by steric hindrance from the ethyl
      groups and partitioning to dissolved organic matter (DOM), thereby shielding
      chlorpyrifos from nucleophilic attack. Significant decreases in reaction rates
      were observed for chlorpyrifos in pore water with high concentrations of DOM.
      Rate enhancement due to other reactive species (e.g., organo-sulfur compounds) in
      pore water was minor for both compounds relative to the influence of bisulfide
      and DOM.

PMID- 27711833
TI  - Arsenic releasing characteristics during the compaction of muddy sediments.
AB  - Muddy sediments are abundant in pore water and capable of preserving a large
      amount of chemicals, such as arsenic. Muddy sediments would transform into
      aquicludes or aquitards during long-term compaction and burial. It remains
      unclear whether the release of arsenic from muddy sediments poses a potential
      contamination risk to groundwater in the adjacent aquifer. An indoor compaction
      simulation experiment was conducted, coupled with an investigation on vertical
      geochemical profiles of muddy sediments in one actual borehole. In this
      experiment, aqueous arsenic in released pore water ranged from 17.5 to 21.3 MUg L
      1 and the accumulated content of the released arsenic was 17.576 MUg during the
      compaction. As(iii) was the main As species in released pore water and had good
      correlations with Fe2+ and Mn. The analysis of the solid phase showed a
      remarkable depletion of Fe-Mn oxide bound arsenic during the compaction. In the
      profiles of the actual borehole, the contents of Fe-Mn oxide bound arsenic also
      exhibited a gradual decreasing trend from shallow to deep. Based on both the
      indoor experiment and the field profile, it can be concluded that the reductive
      dissolution of Fe-Mn oxides took place in arsenic-rich muddy sediments and Fe-Mn
      oxide-bound arsenic transformed into soluble arsenic, then soluble arsenic was
      released into the adjacent aquifer along with the pore water in the long-term
      compaction and burial.

PMID- 27711834
TI  - Discrimination of chiral copper(ii) complexes upon binding of galactonoamidine
      ligands.
AB  - The coordination between N-p-methylbenzyl-d-galactonoamidine, a putative
      transition state analogue of the hydrolyis of glycosidic bonds, and symmetric and
      chiral binuclear copper(ii) complexes was characterized by spectroscopic
      titration, isothermal titration calorimetry, circular dichroism spectroscopy, and
      DFT calculations to elucidate the binding sites in the carbohydrate upon
      coordination to selected metal complexes. For the formation of metal complex
      glyconoamidine assemblies, contributions of the amidine site and of the hydroxyl
      group at C-2 in the glycon of the amidine are noted. The chiral complexes S- and
      R-Cu2bpdbo are discriminated by a third binding site in the carbohydrate that
      leads to higher stability of complexes derived from S-Cu2bpdbo (4-5 kcal mol-1)
      compared to those formed from R-Cu2bpdbo.

PMID- 27711835
TI  - Structure property relationships affecting the proton conductivity in imidazole
      loaded Al-MOFs.
AB  - The structures of the imidazole loaded derivatives of Al-MIL-53 [Al(OH)(1,4-BDC
      (CH3)x)] (x = 0, 1, 2) and CAU-11 ([Al(OH)(SDBA)]) (1,4-H2BDC = terephthalic
      acid; H2SDBA = 4,4'-sulfonyldibenzoic acid) were determined from powder X-ray
      diffraction data. Impedance spectroscopy measurements were carried out to
      evaluate their proton conductivities under anhydrous conditions at temperatures
      up to 110  degrees C. In Al-MIL-53-(CH3)x_HIm (x = 0, 1, 2) the formation of
      hydrogen bonds between the framework and the guest molecules results in a
      decrease in proton conductivity (x0 = 1.7 * 10-6, x1 = 1.9 * 10-8 and x2 = 1.7 *
      10-9 S cm-1 at 110  degrees C and Eact = 0.42, 0.41 and 0.46 eV, for 0, 1 and 2
      CH3-groups, respectively). The highest conductivity has been measured for CAU
      11_HIm with 3.0 * 10-4 S cm-1 at 110  degrees C (Eact = 0.19 eV), where no host
      guest hydrogen bonding interactions are observed.

PMID- 27711836
TI  - Pressure-dependent rate constants for PAH growth: formation of indene and its
      conversion to naphthalene.
AB  - Unraveling the mechanisms for growth of polycyclic aromatic hydrocarbons (PAHs)
      requires accurate temperature- and pressure-dependent rate coefficients for a
      great variety of feasible pathways. Even the pathways for the formation of the
      simplest PAHs, indene and naphthalene, are fairly complex. These pathways provide
      important prototypes for modeling larger PAH growth. In this work we employ the
      ab initio RRKM theory-based master equation approach to predict the rate
      constants involved in the formation of indene and its conversion to naphthalene.
      The reactions eventually leading to indene involve C9Hx (x = 8-11) potential
      energy surfaces (PESs) and include C6H5 + C3H4 (allene and propyne), C6H6 + C3H3,
      benzyl + C2H2, C6H5 + C3H6, C6H6 + C3H5 and C6H5 + C3H5. These predictions allow
      us to make a number of valuable observations on the role of various mechanisms.
      For instance, we demonstrate that reactions which can significantly contribute to
      the formation of indene include phenyl + allene and H-assisted isomerization to
      indene of its major product, 3-phenylpropyne, benzyl + acetylene, and the
      reactions of the phenyl radical with propene and the allyl radical, both
      proceeding via the 3-phenylpropene intermediate. 3-Phenylpropene can be activated
      to a 1-phenylallyl radical, which in turn rapidly decomposes to indene. Next,
      indene can be converted to benzofulvene or naphthalene under typical combustion
      conditions, via its activation by H atom abstraction and methyl substitution on
      the five-membered ring followed by isomerization and decomposition of the
      resulting 1-methylindenyl radical, C10H9 -> C10H8 + H. Alternatively, the same
      region of the C10H9 PES can be accessed through the reaction of benzyl with
      propargyl, C7H7 + C3H3 -> C10H10 -> C10H9 + H, which therefore can also
      contribute to the formation of benzofulvene or naphthalene. Benzofulvene easily
      transforms to naphthalene by H-assisted isomerization. An analysis of the effect
      of pressure on the reaction outcome and relative product yields is given, and
      modified Arrhenius fits of the rate constants are reported for the majority of
      the considered reactions. Ultimately, the implementation of such expressions in
      detailed kinetic models will help quantify the role of these reactions for PAH
      growth in various environments.

PMID- 27711838
TI  - Low-temperature chemistry using the R-matrix method.
AB  - Techniques for producing cold and ultracold molecules are enabling the study of
      chemical reactions and scattering at the quantum scattering limit, with only a
      few partial waves contributing to the incident channel, leading to the
      observation and even full control of state-to-state collisions in this regime. A
      new R-matrix formalism is presented for tackling problems involving low- and
      ultra-low energy collisions. This general formalism is particularly appropriate
      for slow collisions occurring on potential energy surfaces with deep wells. The
      many resonance states make such systems hard to treat theoretically but offer the
      best prospects for novel physics: resonances are already being widely used to
      control diatomic systems and should provide the route to steering ultracold
      reactions. Our R-matrix-based formalism builds on the progress made in
      variational calculations of molecular spectra by using these methods to provide
      wavefunctions for the whole system at short internuclear distances, (a regime
      known as the inner region). These wavefunctions are used to construct collision
      energy-dependent R-matrices which can then be propagated to give cross sections
      at each collision energy. The method is formulated for ultracold collision
      systems with differing numbers of atoms.

PMID- 27711837
TI  - Cyanotoxin degradation activity and mlr gene expression profiles of a
      Sphingopyxis sp. isolated from Lake Champlain, Canada.
AB  - A bacterium capable of degrading five microcystin (MC) variants, microcystin-LR,
      YR, LY, LW and LF at an initial total concentration of 50 MUg l-1 in less than 16
      hours was isolated from Missisquoi Bay, in the south of Quebec, Canada.
      Phylogenetic analysis of the 16S rRNA gene sequence identified the bacterium as
      Sphingopyxis sp., designated strain MB-E. It was shown that microcystin
      biodegradation activity was reduced at acidic and basic pH values. Even though no
      biodegradation occurred at pH values of 5.05 and 10.23, strain MB-E was able to
      degrade MCLR and MCYR at pH 9.12 and all five MCs variants tested at pH 6.1.
      Genomic sequencing revealed that strain MB-E contained the microcystin degrading
      gene cluster, including the mlrA, mlrB, mlrC and mlrD genes, and transcriptomic
      analysis demonstrated that all of these genes were induced during the degradation
      of MCLR alone or in the mixture of all five MCs. This novel transcriptomic
      analysis showed that the expression of the mlr gene cluster was similar for MCLR
      alone, or the mixture of MCs, and appeared to be related to the total
      concentration of substrate. The results suggested that the bacterium used the
      same pathway for the degradation of all MC variants.

PMID- 27711839
TI  - The half-sandwich 18- and 16-electron arene ruthenium iminophosphonamide
      complexes.
AB  - Novel half-sandwich 18e and 16e arene ruthenium iminophosphonamide complexes
      [(eta6-C6Me6)RuCl{(R'N)2PR2}] (3a-c) and [(eta6-C6Me6)Ru{(R'N)2PR2}]+(X-) (4a-c)
      (a, R = Ph, R' = p-Tol; b, R = Et, R' = p-Tol; c, R = Ph, R' = Me. X = BF4, PF6
      or BArF4) were synthesized. The elongated Ru-Cl bond in the 18e complexes is
      shown to dissociate even in apolar solvents to form the corresponding 16e
      cations, which can be readily isolated as salts with non-coordinating anions. The
      coordinatively unsaturated 16e complexes are stable species due to efficient pi
      electron donation from the nitrogen atoms of the zwitterionic NPN-ligand. The
      ruthenium iminophosphonamides are moderately active in the ROMP polymerization of
      norbornene; the 16e complexes 4a,b yield high molecular weight polymers (Mn~ 300
      * 103) with a narrow distribution Mw/Mn~ 1.6, while the 18e complexes 3a,b give
      polymers of lower molecular weight (Mn < 50 * 103) with a wider polydispersity
      index Mw/Mn~ 2.5.

PMID- 27711840
TI  - A simple approach to a new T8-POSS based MRI contrast agent.
AB  - A fast and simple route was developed to synthesize a new T8-silsesquioxane based
      contrast agent for potential application in Magnetic Resonance Imaging. For this
      purpose the novel C2-thiol-functionalized T8-silsesquioxane (3) was constructed
      as a carrier molecule as well as the DOTA based gadolinium(iii) complex (11)
      equipped with allyl terminated linkers was prepared. The linkage of the complexes
      to the T8-silsesquioxane was performed via an UV-light catalyzed thiol-ene click
      reaction within one hour which affords the desired product 13 in a yield of 80%.
      The successful transformation as well as the intactness of the cube was confirmed
      by spectroscopic methods and mass spectrometry. This new and simple approach
      offers a highly effective access to T8-silsesquioxanes functionalized with eight
      metal complexes. Longitudinal relaxivity measurements of compound 13 (9.5 +/- 0.9
      mM-1 s-1) at 3 T in HEPES buffered cell culture medium (physiological conditions)
      show a significant enhancement of r1 per 1 mM gadolinium in comparison to the
      clinically applied contrast agent DotaremTM (3.4 mM-1 s-1). In relation to the
      former reported T8-silsesquioxane based contrast agent Gadoxane G (10.6 mM-1 s-1)
      a similar relaxivity is found. As the T8-core of polyhedral oligosilsesquioxanes
      (POSS) based contrast agents undergoes a hydrolysis process depending on the pH,
      long-term r1 measurements in different solutions (water, cell culture medium and
      HEPES buffered medium) as well as 1H, 1H/29Si HSQC and PGSE diffusion 1H NMR
      spectroscopic investigations on aqueous solutions were performed. In solutions
      featuring an approximately neutral pH (D2O, pD = 7.0; water and HEPES buffered
      medium, pH = 7.4-7.5) contrast agent 13 (t1/2 = 2.4 d, HEPES/medium) shows a
      slower decomposition of the T8-cage in comparison to the previously synthesized
      Gadoxane G (t1/2 = 15 +/- 3 h, HEPES/medium). However, under more basic
      conditions (medium, pH = 8.4-8.5) the decomposition process of 13 is considerably
      accelerated (t1/2 ~ 55-60 min), indicating a higher sensitivity of the T8-cage to
      pH shifts into the basic range similar to Gadoxane G.

PMID- 27711841
TI  - Mechanistic aspects of hydrazine-induced Pt colloid instability and monitoring
      aggregation kinetics with nanoparticle impact electroanalysis.
AB  - Here we investigate the mechanistic aspects of Pt nanoparticle (NP) aggregation
      in solutions typically used for detecting NP/electrode impacts by
      electrocatalytic amplification (ECA). We previously proposed a general mechanism
      for Pt colloid destabilization that involved the participation of both the
      hydrazine redox probe and the pH buffer species as coagulants. Herein the Pt NP
      coagulation and aggregation mechanisms were further investigated with microscopic
      kinetic NP concentration monitoring and zeta potential measurements using
      nanoparticle tracking analysis (NTA), as well as open circuit potential
      experiments with a citrate-treated polycrystalline Pt surface to assess
      electrical double layer potential. After considering the combined results of
      these experiments we propose that the colloidal stability of citrate-capped
      platinum nanoparticles involves much more than the typical physicochemical
      interactions predicted by DLVO theory. A structure based on intermolecular H
      bonding in the citrate capping layer is the most plausible explanation for the
      exceptional stability of large Pt NPs in high ionic strength buffers. Thus, the
      mechanism of Pt NP aggregation includes specific reactive contributions from
      hydrazine. The catalytic decomposition of hydrazine, in particular, is thought to
      occur to some extent at the citrate-coated Pt surface while the citrate remains
      adsorbed. Evolved gases such as ammonia and possible surface bound intermediates
      from Pt-catalyzed decomposition of hydrazine may disrupt the stability of the
      citrate layer, causing colloidal instability and thus promoting Pt NP
      coagulation. In the closing section, we demonstrate nanoparticle impact
      electroanalysis by ECA detection as a method to quantify Pt NP concentration with
      adequate time resolution for monitoring the kinetics of Pt NP coagulation.

PMID- 27711842
TI  - Clioquinol-ruthenium complex impairs tumour cell invasion by inhibiting cathepsin
      B activity.
AB  - Over the past few years, the organometalled compounds, including ruthenium,
      gained a lot of attention as anticancer agents. We report on the clioquinol
      ruthenium complex [Ru(eta6-p-cymene)(Cq)Cl] as a potent inhibitor of cathepsin B,
      a lysosomal cysteine peptidase, involved in tumour cell invasion and metastasis.
      In the low micromolar concentration range, the clioquinol-ruthenium complex did
      not exhibit cytotoxic effects on MCF-10A neoT and U-87 MG cells; it did, however,
      significantly reduce their ability for extracellular matrix degradation and
      invasiveness in two independent cell-based models, measuring either electrical
      impedance in real time or the growth of multicellular tumour spheroids implanted
      in Matrigel, a model representing the extracellular matrix. These results
      establish ruthenium based organometallic compounds as promising candidates for
      further pre-clinical studies as anticancer therapeutics.

PMID- 27711843
TI  - Ionic-liquid-assisted synthesis of the phosphorus interhalides [PBr4][IBr2] and
      [PBr4][I5Br7].
AB  - The phosphorus interhalides [PBr4][IBr2] (1) and [PBr4]2[I5Br7] (2) were prepared
      by reaction of PBr5 and the interhalogen IBr in the ionic liquid [MeBu3N][N(Tf)2]
      (N(Tf)2: bis(trifluoromethylsulfonyl)amide). [PBr4][IBr2] (1) consists of
      tetrahedral [PBr4]+ cations and linear [IBr2]- anions. [PBr4]2[I5Br7] (2) also
      contains [PBr4]+ cations as well as the iodine bromide anion [I5Br7]2-. The
      latter represents the yet largest known polyiodinebromide. Moreover, (2) shows
      remarkable halogen release (IBr and Br2) of 96.8 wt% below 300  degrees C. For
      the ternary system P-Br-I, (1) and (2) are the first compounds that were
      characterized by crystal structure analysis. Composition, bonding situation and
      properties were further validated by energy dispersive X-ray (EDX) analysis,
      thermogravimetry (TG) and Raman spectroscopy.

PMID- 27711844
TI  - Femtosecond photodissociation dynamics of 1,4-diiodobenzene by gas-phase X-ray
      scattering and photoelectron spectroscopy.
AB  - We present a multifaceted investigation into the initial photodissociation
      dynamics of 1,4-diiodobenzene (DIB) following absorption of 267 nm radiation. We
      combine ultrafast time-resolved photoelectron spectroscopy and X-ray scattering
      experiments performed at the Linac Coherent Light Source (LCLS) to study the
      initial electronic excitation and subsequent rotational alignment, and interpret
      the experiments in light of Complete Active Space Self-Consistent Field (CASSCF)
      calculations of the excited electronic landscape. The initially excited state is
      found to be a bound 1B1 surface, which undergoes ultrafast population transfer to
      a nearby state in 35 +/- 10 fs. The internal conversion most likely leads to one
      or more singlet repulsive surfaces that initiate the dissociation. This initial
      study is an essential and prerequisite component of a comprehensive study of the
      complete photodissociation pathway(s) of DIB at 267 nm. Assignment of the
      initially excited electronic state as a bound state identifies the mechanism as
      predissociative, and measurement of its lifetime establishes the time between
      excitation and initiation of dissociation, which is crucial for direct comparison
      of photoelectron and scattering experiments.

PMID- 27711845
TI  - Single oxygen generation sensitized by
      spiro(dipyridinogermole)(dithienogermole)s.
AB  - Three spiro(dipyridinogermole)(dithienogermole) derivatives (1-3), including
      newly prepared spiro(dipyridinogermole)[di(2-pyridyl)dithienogermole] (3), were
      examined as photosensitizers for singlet oxygen (1O2) generation in
      dichloromethane-methanol. Irradiation of their air-saturated solutions led to the
      generation of 1O2, which was readily trapped by well-known scavengers,
      dihydronaphthoquinone (DHN) and diphenylisobenzofuran (DPBF).
      Spiro(dipyridinogermole)[bis(n-hexylbithiophenyl)dithienogermole] (2) showed the
      best performance with a first-order rate constant that was higher than that of
      tetraphenylporphyrin (TPP), an efficient photosensitizer for 1O2 generation. This
      is ascribable to the efficient intersystem crossing characteristic of the
      dipyridinogermole unit. The quantum yield of 1O2 generation was phiDelta = 0.72
      for 2, relative to that for rose bengal (RB) in methanol as reference (phiDelta =
      0.8).

PMID- 27711846
TI  - Synthesis, structures, and magnetic properties of metal-organic polyhedra based
      on unprecedented {V7} isopolyoxometalate clusters.
AB  - Two isostructural vanadium-based metal-organic polyhedra (denoted as VMOP-16 and
      VMOP-17) were synthesized by a solvothermal method, which are built from
      unprecedented {V7} isopolyoxometalate clusters and dicarboxylate ligands. To our
      knowledge, the {V7} second building unit is reported for the first time and
      features the highest nuclearity of vanadium-oxygen clusters compared with
      reported vanadium-based MOPs.

PMID- 27711847
TI  - Atom tunnelling in the reaction NH3+ + H2 -> NH4+ + H and its astrochemical
      relevance.
AB  - The title reaction is involved in the formation of ammonia in the interstellar
      medium. We have calculated thermal rates including atom tunnelling using
      different rate theories. Canonical variational theory with microcanonically
      optimised multidimensional tunnelling was used for bimolecular rates, modelling
      the gas-phase reaction and also a surface-catalysed reaction of the Eley-Rideal
      type. Instanton theory provided unimolecular rates, which model the Langmuir
      Hinshelwood type surface reaction. The potential energy was calculated on the
      CCSD(T)-F12 level of theory on the fly. We report thermal rates and H/D kinetic
      isotope effects. The latter have implications for observed H/D fractionation in
      molecular clouds. Tunnelling causes rate constants to be sufficient for the
      reaction to play a role in interstellar chemistry even at cryogenic temperature.
      We also discuss intricacies and limitations of the different tunnelling
      approximations to treat this reaction, including its pre-reactive minimum.

PMID- 27711849
TI  - Novel photochemistry of molecular polaritons in optical cavities.
AB  - Violations of the Born-Oppenheimer approximation (BOA) and the consequent
      nonadiabatic dynamics have long been an object of intense study. Recently, such
      dynamics have been induced via strong coupling of the molecule to a high
      amplitude (spatially confined) mode of the electromagnetic field in optical
      cavities. However, the effects of a cavity on a pre-existing avoided crossing or
      conical intersection are relatively unexplored. The dynamics of molecules dressed
      by cavity modes are usually calculated by invoking the rotating wave
      approximation (RWA), which greatly simplifies the calculation but breaks down
      when the cavity mode frequency is higher than the relevant material frequencies.
      We develop a protocol for computing curve crossing dynamics in an optical cavity
      by exploiting a recently-developed method of solving the quantum Rabi model
      without invoking the RWA. The method is demonstrated for sodium iodide.

PMID- 27711848
TI  - Metabolism and growth inhibitory activity of cranberry derived flavonoids in
      bladder cancer cells.
AB  - In the present study, anti-proliferative activities of cranberry derived
      flavonoids and some of their in vivo metabolites were evaluated using a panel of
      human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic
      immortalized human uroepithelial cells (SV-HUC). Among the compounds tested,
      quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and
      quercetin showed strong concentration-dependent cell growth inhibitory activities
      in bladder cancer cells with IC50 values in a range of 8-92 MUM. Furthermore,
      isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even
      at very high concentrations (>200 MUM) compared to bladder cancer cells,
      indicating that their cytotoxicity is selective for cancer cells. To determine
      whether the differential cell growth inhibitory effects of isomeric flavonoids
      quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside)
      (inactive) are related to their metabolism by the cancer cells, SW-780 cells were
      incubated with these compounds and their metabolism was examined by LC-MS/MS.
      Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less
      metabolic biotransformation (methylation, glucuronidation and quinone formation).
      These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the
      active forms of quercetin in prevention of bladder cancer in vivo and emphasize
      the importance of metabolism for the prevention of bladder cancer by diets rich
      in cranberries.

PMID- 27711850
TI  - Effect of tomato juice consumption on the plasmatic lipid profile, hepatic HMGCR
      activity, and fecal short chain fatty acid content of rats.
AB  - The aims of the present study were to ascertain, indirectly, the prebiotic role
      of tomato juice, by analyzing its effect on the content of short chain fatty
      acids (SCFA) in feces of rats, and to determine the plausible mechanisms related
      to the hypocholesterolemic effects of tomato juice and lycopene, evaluating the
      activity of hepatic HMGCR and the formation of propionic acid. Two commercially
      available tomato juices with differing contents of lycopene (low and high
      lycopene contents: Llyc and Hlyc tomato juices) were used. Sprague-Dawley male
      rats were randomly divided into three experimental groups (n = 8): control group,
      normal diet and water; group 1, normal diet and Llyc tomato juice; and group 2,
      normal diet and Hlyc tomato juice, which were fed ad libitum for three weeks.
      Feces were collected at the beginning and the end of the study to determine SCFA,
      and blood and liver were obtained (after sacrificing the animals) to analyze the
      lipid plasmatic parameters and the HMGCR activity and total cholesterol,
      respectively. No significant differences were observed in the plasmatic
      parameters, except that HDL-cholesterol increased significantly after consumption
      of both tomato juices. Lycopene was accumulated in the liver in proportion to the
      amount ingested, and was observed to have an inhibitory effect on the HMGCR
      enzyme, according to the amount of lycopene in the liver. In relation to the SCFA
      in feces, no differences were observed in acetate and propionate after the
      consumption of tomato juice, but a significant increase in butyrate was observed
      in group 2 after the intake of Hlyc tomato juice. The content of this carboxylic
      acid together with excreted lycopene in feces could have a beneficial effect on
      colonic cells.

PMID- 27711851
TI  - Dissipative dynamics at conical intersections: simulations with the hierarchy
      equations of motion method.
AB  - The effect of a dissipative environment on the ultrafast nonadiabatic dynamics at
      conical intersections is analyzed for a two-state two-mode model chosen to
      represent the S2(pipi*)-S1(npi*) conical intersection in pyrazine (the system)
      which is bilinearly coupled to infinitely many harmonic oscillators in thermal
      equilibrium (the bath). The system-bath coupling is modeled by the Drude spectral
      function. The equation of motion for the reduced density matrix of the system is
      solved numerically exactly with the hierarchy equation of motion method using
      graphics-processor-unit (GPU) technology. The simulations are valid for arbitrary
      strength of the system-bath coupling and arbitrary bath memory relaxation time.
      The present computational studies overcome the limitations of weak system-bath
      coupling and short memory relaxation time inherent in previous simulations based
      on multi-level Redfield theory [A. Kuhl and W. Domcke, J. Chem. Phys. 2002, 116,
      263]. Time evolutions of electronic state populations and time-dependent reduced
      probability densities of the coupling and tuning modes of the conical
      intersection have been obtained. It is found that even weak coupling to the bath
      effectively suppresses the irregular fluctuations of the electronic populations
      of the isolated two-mode conical intersection. While the population of the upper
      adiabatic electronic state (S2) is very efficiently quenched by the system-bath
      coupling, the population of the diabatic pipi* electronic state exhibits long
      lived oscillations driven by coherent motion of the tuning mode.
      Counterintuitively, the coupling to the bath can lead to an enhanced lifetime of
      the coherence of the tuning mode as a result of effective damping of the highly
      excited coupling mode, which reduces the strong mode-mode coupling inherent to
      the conical intersection. The present results extend previous studies of the
      dissipative dynamics at conical intersections to the nonperturbative regime of
      system-bath coupling. They pave the way for future first-principles simulations
      of femtosecond time-resolved four-wave-mixing spectra of chromophores in
      condensed phases which are nonperturbative in the system dynamics, the system
      bath coupling as well as the field-matter coupling.

PMID- 27711852
TI  - Microbial toxicity and biodegradability of perfluorooctane sulfonate (PFOS) and
      shorter chain perfluoroalkyl and polyfluoroalkyl substances (PFASs).
AB  - Perfluorooctane sulfonate (PFOS) and related perfluoroalkyl and polyfluoroalkyl
      substances (PFASs) are emerging contaminants that have been widely applied in
      consumer and industrial applications for decades. However, PFOS has raised public
      concern due to its high bioaccumulative character, environmental persistence, and
      toxicity. Shorter PFASs such as perfluorobutane sulfonate (PFBS) and
      polyfluoroalkyl compounds have been proposed as alternatives to PFOS but it is
      unclear whether these fluorinated substances pose a risk for public health and
      the environment. The objective of this research was to investigate the microbial
      toxicity and the susceptibility to microbial degradation of PFOS and several
      related fluorinated compounds, i.e., short-chain perfluoroalkyl and
      polyfluoroalkyl sulfonic and carboxylic acids. None of the compounds tested were
      toxic to the methanogenic activity of anaerobic wastewater sludge even at very
      high concentrations (up to 500 mg L-1). All PFASs evaluated were highly resistant
      to microbial degradation. PFOS was not reductively dehalogenated by the anaerobic
      microbial consortium even after very long periods of incubation (3.4 years).
      Similarly, the tested short chain perfluoroalkyl substances (i.e., PFBS and
      trifluoroacetic acid) and a polyfluoroalkyl PFOS analogue, 6 : 2 fluorotelomer
      sulfonic acid (FTSA) were also resistant to anaerobic biodegradation. Likewise,
      no conclusive evidence of microbial degradation was observed under aerobic
      conditions for any of the short-chain perfluoroalkyl and polyfluoroalkyl
      carboxylic acids tested after 32 weeks of incubation. Collectively, these results
      indicate that PFOS and its alternatives such as short chain perfluoroalkyl
      sulfonates and carboxylates and their polyfluorinated homologues are highly
      resistant to microbial degradation.

PMID- 27711853
TI  - Strong-field-induced wave packet dynamics in carbon dioxide molecule.
AB  - Temporal evolution of electronic and nuclear wave packets created in strong-field
      excitation of the carbon dioxide molecule is studied employing momentum-resolved
      ion spectroscopy and channel-selective Fourier analysis. Combining the data
      obtained with two different pump-probe set-ups, we observed signatures of
      vibrational dynamics in both, ionic and neutral states of the molecule. We
      consider far-off-resonance two-photon Raman scattering to be the most likely
      mechanism of vibrational excitation in the electronic ground state of the neutral
      CO2. Using the measured phase relation between the time-dependent yields of
      different fragmentation channels, which is consistent with the proposed
      mechanism, we suggest an intuitive picture of the underlying vibrational
      dynamics. For ionic states, we found signatures of both, electronic and
      vibrational excitations, which involve the ground and the first excited
      electronic states, depending on the particular final state of the fragmentation.
      While our results for ionic states are consistent with the recent observations by
      Erattupuzha et al. [J. Chem. Phys.144, 024306 (2016)], the neutral state
      contribution was not observed there, which we attribute to a larger bandwidth of
      the 8 fs pulses we used for this experiment. In a complementary measurement
      employing longer, 35 fs pulses in a 30 ps delay range, we study the influence of
      rotational excitation on our observables, and demonstrate how the coherent
      electronic wave packet created in the ground electronic state of the ion
      completely decays within 10 ps due to the coupling to rotational motion.

PMID- 27711854
TI  - Towards efficient time-resolved X-ray absorption studies of electron dynamics at
      photocatalytic interfaces.
AB  - We present a picosecond time-resolved X-ray absorption spectroscopy (tr-XAS)
      setup designed for synchrotron-based studies of interfacial photochemical
      dynamics. The apparatus combines a high power, variable repetition rate
      picosecond laser system with a time-resolved X-ray fluorescence yield detection
      technique. Time-tagging of the detected fluorescence signals enables the parallel
      acquisition of X-ray absorption spectra at a variety of pump-probe delays
      employing the well-defined time structure of the X-ray pulse trains. The
      viability of the setup is demonstrated by resolving dynamic changes in the fine
      structure near the O1s X-ray absorption edge of cuprous oxide (Cu2O) after photo
      excitation with a 355 nm laser pulse. Two distinct responses are detected. A
      pronounced, quasi-static, reversible change of the Cu2O O1s X-ray absorption
      spectrum by up to ~30% compared to its static line shape corresponds to a
      redshift of the absorption edge by ~1 eV. This value is small compared to the 2.2
      eV band gap of Cu2O but in agreement with previously published results. The
      lifetime of this effect exceeds the laser pulse-to-pulse period of 8 MUs,
      resulting in a quasi-static spectral change that persists as long as the sample
      is exposed to the laser light, and completely vanishes once the laser is blocked.
      Additionally, a short-lived response corresponding to a laser-induced shift of
      the main absorption line by ~2 eV to lower energies appears within <200 ps and
      decays with a characteristic timescale of 43 +/- 5 ns. Both the picosecond rise
      and nanosecond decay of this X-ray response are simultaneously captured by making
      use of a time-tagging approach - highlighting the prospects of the experimental
      setup for efficient probing of the electronic and structural dynamics in
      photocatalytic systems on multiple timescales.

PMID- 27711855
TI  - Synthesis, crystal structure and characterization of novel open framework CHA
      type aluminophosphate involving a chiral diamine.
AB  - A highly crystalline new precursor of CHA-type zeolite AlPO4-34 was obtained by
      using an aluminophosphate gel with a chiral diamine [(S)-(+)-1-(2
      pyrrolidinylmethyl)pyrrolidine; C9H18N2] as an organic structure directing agent
      under hydrothermal synthesis conditions. This precursor (called GAM-1) was
      changed into the zeolite AlPO4-34 which had a high porosity (the Brunauer-Emmett
      Teller (BET) surface area is approximately 700 m3 g-1) using calcination. The GAM
      1 obtained was characterized by various measurements, e.g., powder X-ray
      diffraction, scanning electron microscopy, and solid-state nuclear magnetic
      resonance spectroscopy, and so on. Structure determination from powder
      diffraction data revealed that the new precursor GAM-1 has triclinic symmetry
      [space group P1[combining macron], a = 9.16535(11) A, b = 9.23042(11) A, c =
      9.29228(11) A, alpha = 79.8243(7) degrees , beta = 87.4593(7) degrees , gamma =
      86.5365(7) degrees ] and the chemical formula was estimated to be:
      |Al6P6O24H2F2|(C9H18N2).2.5(H2O). It also revealed that a two edge sharing AlO4F2
      octahedron with an [triple bond, length as m-dash]Al-F-Al[triple bond, length as
      m-dash] bridge was included in the framework. GAM-1 was transformed into AlPO4-34
      with rhombohedral symmetry (R3[combining macron]) by elevating temperature to
      over 400  degrees C. At high temperatures, AlO4F2 octahedron connectivity was
      changed into an AlO4 tetrahedron. The crystal structure of the dehydrated AlPO4
      34 changed back to a triclinic symmetry (P1) model again after rehydration in the
      atmosphere.

PMID- 27711857
TI  - Reactive trajectories of the Ru2+/3+ self-exchange reaction and the connection to
      Marcus' theory.
AB  - Outer sphere electron transfer between two ions in aqueous solution is a rare
      event on the time scale of first principles molecular dynamics simulations. We
      have used transition path sampling to generate an ensemble of reactive
      trajectories of the self-exchange reaction between a pair of Ru2+ and Ru3+ ions
      in water. To distinguish between the reactant and product states, we use as an
      order parameter the position of the maximally localised Wannier center associated
      with the transferring electron. This allows us to align the trajectories with
      respect to the moment of barrier crossing and compute statistical averages over
      the path ensemble. We compare our order parameter with two typical reaction
      coordinates used in applications of Marcus theory of electron transfer: the
      vertical gap energy and the solvent electrostatic potential at the ions.

PMID- 27711856
TI  - Attosecond science in atomic, molecular, and condensed matter physics.
AB  - Attosecond science represents a new frontier in atomic, molecular, and condensed
      matter physics, enabling one to probe the exceedingly fast dynamics associated
      with purely electronic dynamics in a wide range of systems. This paper presents a
      brief discussion of the technology required to generate attosecond light pulses
      and gives representative examples of attosecond science carried out in several
      laboratories. Attosecond transient absorption, a very powerful method in
      attosecond science, is then reviewed and several examples of gas phase and
      condensed phase experiments that have been carried out in the Leone/Neumark
      laboratories are described.

PMID- 27711858
TI  - Designed intramolecular blocking of the spin crossover of an Fe(ii) complex.
AB  - A ligand derived from 1,3bpp (2-(pyrazol-1-yl)-6-(pyrazol-3-yl)-pyridine) has
      been prepared to prove that the spin crossover (SCO) of an Fe(ii) complex can be
      blocked by means of intramolecular interactions not related to the crystal field.
      Calculations show that the blocking is caused by the energy penalty incurred by
      the rotation of a phenyl ring, needed to avoid steric hindrance upon SCO.

PMID- 27711859
TI  - Novel synthesis of a four-electron-reduced ruthenium(ii) NADH-type complex under
      water-gas-shift reaction conditions.
AB  - A four-electron-reduced ruthenium(ii) NADH-type complex, [Ru(bbnpH4)(CO)2Cl](PF6)
      (bbnpH4 = 2,2'-(4-(tert-butyl)pyridine-2,6-diyl)bis(5,10
      dihydrobenzo[b][1,5]naphthyridine)), has been successfully synthesized by mixing
      an NAD+-type ligand, bbnp (bbnp = 2,2'-(4-(tert-butyl)pyridine-2,6
      diyl)bis(benzo[b][1,5]naphthyridine)), and [Ru(CO)2Cl2] under moderate water-gas
      shift reaction conditions, which has been fully characterized by single-crystal X
      ray structure analysis, ESI-TOF mass spectrometry, and NMR spectroscopy.

PMID- 27711861
TI  - A multi-responsive luminescent sensor based on a super-stable sandwich-type
      terbium(iii)-organic framework.
AB  - A super-stable multifunctional terbium(iii)-organic framework, namely {[Tb(TATAB)
      (H2O)2].NMP.H2O}n (Tb-MOF, H3TATAB = 4,4',4''-s-triazine-1,3,5-triyltri-m
      aminobenzoic acid, NMP = N-methyl-2-pyrrolidone) was synthesized. Tb-MOF exhibits
      a 2D sql structure with binuclear [Tb2(COO)4(H2O)4]2+ units as 4-connected nodes,
      and free water and NMP molecules are inserted between 2D layers through hydrogen
      bonding interactions, forming a sandwich-type architecture. Observably, such a
      framework remains intact in a remarkable variety of environments such as common
      solvents and aqueous solutions with metal cations and inorganic anions, as well
      as with a pH ranging from 1 to 13. In particular, Tb-MOF can not only detect
      small organic molecules, metal cations and inorganic anions with high sensitivity
      and high selectivity, but also can accurately detect explosive 2-nitrophenol, 3
      nitrophenol, 4-nitrophenol and 2,4,6-trinitrophenol in water. Its luminescence
      quenching response to Fe3+ and Cr2O72- ions can be explained in terms of the
      competitive absorption mechanism. In addition, the luminescence intensity of Tb
      MOF is strongly correlated with the pH value in a pH range from 1 to 13. Thus,
      this material can be potentially used as a multi-responsive luminescent sensor.

PMID- 27711860
TI  - Synthesis, up-conversion luminescence and thermometry of Yb3+/Er3+ co-doped
      La2.4Mo1.6O8 phosphors.
AB  - Yb3+/Er3+ co-doped La2.4Mo1.6O8 up-conversion phosphors with thermometric
      properties were synthesized by a conventional solid-state reaction. The optimal
      synthesis conditions for the pure phase have been determined by varying the types
      and contents of fluxes. Structural studies verify that all samples retain the
      same face-centered cubic structure, and the morphology via SEM observation also
      verified the cubic-like crystal growth behaviour. Yb3+/Er3+ co-doped La2.4Mo1.6O8
      phosphors mainly emit green emission peaks, ascribed to the emission from the
      excited states 2H11/2 and 4S3/2 to the ground state 4I15/2 of Er3+ ion, and the
      weak red emission from the excited state 4F9/2 to the ground state 4I15/2 of Er3+
      ion when they are excited by 980 nm laser diodes. The up-conversion process has
      been discussed in detail by pump-power dependence of luminescence intensities and
      further explained via the energy level diagram. The temperature-dependence
      properties of La2.4Mo1.6O8 phosphors were investigated in detail, which show
      their potential prospect in temperature-sensing applications.

PMID- 27711862
TI  - Electrochemistry at single bimetallic nanoparticles - using nano impacts for
      sizing and compositional analysis of individual AgAu alloy nanoparticles.
AB  - The increasing interest in producing bimetallic nanoparticles and utilizing them
      in modern technologies sets the demand for fast and affordable characterization
      of these materials. To date Scanning Transmission Electron Microscopy (STEM)
      coupled to energy dispersive X-ray spectroscopy is usually used to determine the
      size and composition of alloy nanoparticles, which is time-consuming and
      expensive. Here electrochemical single nanoparticle analysis is presented as an
      alternative approach to infer the particle size and composition of alloy
      nanoparticles, directly in a dispersion of these particles. As a proof of
      concept, 14 nm sized Ag0.73Au0.27 alloy nanoparticles are analyzed using a
      combination of chronoamperometric single nanoparticle analysis and cyclic
      voltammetry ensemble studies. It is demonstrated that the size, the alloying and
      the composition can all be inferred using this approach. Thus, the
      electrochemical characterization of single bimetallic alloy nanoparticles is
      suggested here as a powerful and convenient complement or alternative to TEM
      characterization of alloy nanoparticles.

PMID- 27711863
TI  - Bacterial components are the major contributors to the macrophage stimulating
      activity exhibited by extracts of common edible mushrooms.
AB  - Recent studies have indicated that a major contributor to the innate immune
      enhancing properties of some medicinal plants is derived from the cell wall
      components of bacteria colonizing these plants. The purpose of the current study
      was to assess if the bacteria present within edible and medicinal mushrooms
      substantially contribute to the innate immune stimulating potential of these
      mushrooms. Whole mushrooms from thirteen types of edible fungi and individual
      parts from Agaricus bisporus were analyzed for in vitro macrophage activation as
      well as bacterial lipopolysaccharides (LPS) content, cell load, and community
      composition. Substantial variation between samples was observed in macrophage
      activation (over 500-fold), total bacterial load (over 200-fold), and LPS content
      (over 10 million-fold). Both LPS content (rho = 0.832, p < 0.0001) and total
      bacterial load (rho = 0.701, p < 0.0001) correlated significantly with macrophage
      activation in the whole mushroom extracts. Extract activity was negated by
      treatment with NaOH, conditions that inactivate LPS and other bacterial
      components. Significant correlations between macrophage activation and total
      bacterial load (rho = 0.723, p = 0.0001) and LPS content (rho = 0.951, p <
      0.0001) were also observed between different tissues of Agaricus bisporus.
      Pseudomonas and Flavobacterium were the most prevalent genera identified in the
      different tissue parts and these taxa were significantly correlated with in vitro
      macrophage activation (rho = 0.697, p < 0.0001 and rho = 0.659, p = 0.0001,
      respectively). These results indicate that components derived from mushroom
      associated bacteria contribute substantially to the innate immune enhancing
      activity exhibited by mushrooms and may result in similar therapeutic actions as
      reported for ingestion of bacterial preparations such as probiotics.

PMID- 27711864
TI  - Potassium uranyl borate 3D framework compound resulted from temperature directed
      hydroborate condensation: structure, spectroscopy, and dissolution studies.
AB  - The equatorial coordination nature of the uranyl unit has resulted in only three
      uranyl borate 3D framework compounds reported so far formed from boric acid flux
      reactions conducted at 190  degrees C while all others are 2D layers. Here in
      this work, by increasing the reaction temperature to 250  degrees C, a new
      potassium uranyl borate K[(UO2)B6O10(OH)] (KUBO-4) framework compound is
      synthesized that shares the same layer topology with the previously reported 2D
      layered KUBO-1. The 3D structure of KUBO-4 is achieved by interlayer hydroborate
      condensation. The KUBO-4 was further characterized with single crystal XRD, SHG
      and fluorescence spectra, and TG/DSC measurements. A deep understanding regarding
      the dissolution behaviours of uranyl borate is achieved via solubility studies of
      the KUBO-1 and KUBO-4 performed using a combination of ICP-MS, powder XRD, and
      fluorescence spectroscopy techniques. The results confirm the lack of stability
      of borates in aqueous solutions with the presence of coordinating ligands in the
      environment regardless of the structure types.

PMID- 27711865
TI  - Low-temperature atomic layer deposition of crystalline manganese oxide thin
      films.
AB  - We present a new low-temperature atomic layer deposition (ALD) process based on
      Mn2(CO)10 and ozone as precursors to fabricate crystalline alpha-Mn2O3 and Mn3O4
      thin films; the phase composition is controlled by the deposition temperature
      such that the former phase forms in the range 60-100  degrees C and the latter in
      the range 120-160  degrees C. In both cases an appreciably high growth rate of
      ~1.2 A per cycle is achieved. The spinel-structured Mn3O4 thin films are shown to
      be ferrimagnetic with the transition temperature determined to be at ~47 K.

PMID- 27711866
TI  - The role of ammonia in promoting ammonia borane synthesis.
AB  - Ammonia promotes the synthesis of pure ammonia borane (AB) in excellent yields
      from sodium borohydride and ammonium sulfate in tetrahydrofuran under ambient
      conditions. An examination of the influence of added ammonia reveals that it is
      incorporated into the product AB, contrary to its perceived function as a
      catalyst or a co-solvent. Mechanistic studies point to a nucleophilic attack by
      ammonia on ammonium borohydride with concurrent dehydrogenation to yield AB.

PMID- 27711867
TI  - Observation of multi-channel non-adiabatic dynamics in aniline derivatives using
      time-resolved photoelectron imaging.
AB  - We present results from a recent time-resolved photoelectron imaging (TRPEI)
      study investigating the non-adiabatic relaxation dynamics of N,N-dimethylaniline
      (N,N-DMA) and 3,5-dimethylaniline (3,5-DMA) following excitation at 240 nm.
      Analysis of the experimental data is supported by ab initio coupled-cluster
      calculations evaluating excited state energies and the evolution of several
      excited state physical properties as a function of N-H/N-CH3 bond extension - a
      critical reaction coordinate. The use of site-selective methylation brings
      considerable new insight to the existing body of literature concerning
      photochemical dynamics in the related system aniline at similar excitation
      wavelengths. The present work also builds on our own previous investigations in
      the same species at 250 nm. The TRPEI method provides highly differential energy-
      and angle-resolved data and, in particular, the temporal evolution of the
      photoelectron angular distributions afforded by the imaging approach offers much
      of the new dynamical information. In particular, we see no clear evidence of the
      second excited 2pipi* state non-adiabatically coupling to the lower-lying
      S1(pipi*) state or the mixed Rydberg/valence S2(3s/pisigma*) state. This, in
      turn, potentially raises some unresolved questions about the overall nature of
      the dynamics operating in these systems, especially in regard to the 2pipi*
      state's ultimate fate. More generally, the findings for the aromatic systems N,N
      DMA and 3,5-DMA, taken along with our recent TRPEI results for several aliphatic
      amine species, highlight interesting questions about the nature of electronic
      character evolution in mixed Rydberg-valence states as a function of certain key
      bond extensions and the extent of system conjugation. We begin exploring these
      ideas computationally for a systematically varied series of tertiary amines.

PMID- 27711868
TI  - Dehydrogenation of benzyl alcohol with N2O as the hydrogen acceptor catalyzed by
      the rhodium(i) carbene complex: insights from quantum chemistry calculations.
AB  - The detailed mechanisms of the dehydrogenation of benzyl alcohol with N2O as the
      hydrogen acceptor catalyzed by the rhodium(i) carbene complex for the formation
      of the corresponding carboxylic acid or ester have been investigated via density
      functional theory (DFT) calculations at the M06 level of theory. Three cycles
      were considered for the formation of benzaldehyde, benzyl benzoate and benzoic
      acid. On the basis of the calculations, the rate-determining step for these three
      cycles is involved in N2O activation by the rhodium ammine hydride complex with
      an activation barrier of only 22.6 kcal mol-1, which is different from the
      previous mechanism proposed by Gianetti and co-workers, where the hydride is
      transferred from the Rh atom to the oxygen atom of N2O with a barrier of 30.5
      kcal mol-1. In addition, the calculations also demonstrated that one more N2O is
      necessary to give benzoic acid, and the reaction can only take place under
      anhydrous conditions. Present calculations are in good agreement with the
      experimental observations and provide new insights into the dehydrogenation of
      benzyl alcohol with N2O as the hydrogen acceptor.

PMID- 27711869
TI  - {[Ir3(cod)3(MU3-S)2](MU3-S)SnCl}2 - a ternary Ir-Sn-S cluster with the iridium
      atoms in three different chemical environments.
AB  - Reactions of Sn-S clusters with [IrCl(cod)]2 afforded an Ir-Sn-S cluster with
      unprecedented topology, {[Ir3(cod)3(MU3-S)2](MU3-S)SnCl}2, in which two [Ir3S2]
      units and a central [Sn2S2] unit are connected via Ir-S and Ir-Sn bonds. Each of
      the crystallographically independent Ir atoms exhibits a specific chemical
      environment. Quantum chemical studies shed light on the electronic structure of
      the multinary cluster and the Ir-Sn bonds.

PMID- 27711870
TI  - Comparison of lipases for in vitro models of gastric digestion: lipolysis using
      two infant formulas as model substrates.
AB  - The aim of this study was to find a lipase suitable as a surrogate for Human
      Gastric Lipase (HGL), since the development of predictive gastrointestinal
      lipolysis models are hampered by the lack of a lipase with similar digestive
      properties as HGL. Three potential surrogates for HGL; Rhizopus Oryzae Lipase
      (ROL), Rabbit Gastric Lipase (RGL) and recombinant HGL (rHGL), were used to
      catalyze the in vitro digestion of two infant formulas (a medium-chain
      triacylglyceride enriched formula (MC-IF) and a predominantly long-chain
      triacylglyceride formula (LC-IF)). Digesta were withdrawn after 0, 5, 15, 30, 60
      min of gastric digestion and after 90 or 180 min of intestinal digestion with or
      without the presence of pancreatic enzymes, respectively. The digesta were
      analyzed by scanning electron microscopy and gas chromatography to quantify the
      release of fatty acids (FAs). Digestions of both formulas, catalyzed by ROL,
      showed that the extent of gastric digestion was higher than expected from
      previously published in vivo data. ROL was furthermore insensitive to FA chain
      length and all FAs were released at the same pace. RGL and rHGL favoured the
      release of MC-FAs in both formulas, but rHGL did also release some LC-FAs during
      digestion of MC-IF, whereas RGL only released MC-FAs. Digestion of a MC-IF by HGL
      in vivo showed that MC-FAs are preferentially released, but some LC-FAs are also
      released. Thus of the tested lipase rHGL replicated the digestive properties of
      HGL the best and is a suitable surrogate for HGL for use in in vitro
      gastrointestinal lipolysis models.

PMID- 27711872
TI  - Demonstration of intramolecular energy transfer in asymmetric bimetallic
      ruthenium(ii) complexes.
AB  - A new family of bimetallic Ru(ii) complexes derived from an asymmetric bridging
      ligand (tpy-Hbzim-dipy) consisting of both bipyridine and terpyridine chelating
      sites covalently connected via phenyl-imidazole spacer were designed in this work
      to demonstrate intramolecular energy transfer from one component to the other in
      asymmetric dyads. To fine tune the photo-redox properties, both bidentate and
      tridentate terminal ligands in the complexes were varied systematically. Both
      steady state and time-resolved luminescence spectral results indicated photo
      induced intramolecular energy transfer from the excited MLCT state of the
      [(bpy/phen)2RuII(dipy-Hbzim-tpy)] component to the MLCT state of the tpy
      containing unit [(dipy-Hbzim-tpy)RuII(tpy-PhCH3/H2pbbzim)] in dyads with rate
      constant values on the order of 106-107 s-1. Temperature-dependent luminescence
      studies indicated an enhancement in the luminescence intensity and excited state
      lifetimes upon decreasing the temperature.

PMID- 27711873
TI  - Synthesis of a new class of silsesquioxanes with alkynyl and germyl
      functionality.
AB  - Although there are a variety of functional compounds in the vast family of
      silsesquioxanes (POSS), the number of protocols describing specific
      monosubstituted silsesquioxanes is limited. There are even fewer reports on
      alkynyl and/or germyl functionalities appearing together with the POSS compounds.
      Here, a series of novel kinds of cubic monosubstituted POSS bearing alkynyl and
      germyl functionality in one molecule are reported. These compounds were
      synthesized by effective germylative coupling of terminal alkynes with
      vinylgermanes in the presence of a Ru-H complex. The structures of the products
      were determined. Moreover, stoichiometric reactions of a complex possessing Ru-Ge
      were also performed to propose the general mechanistic scheme of this reaction.

PMID- 27711871
TI  - On the mechanism of electrochemical vesicle cytometry: chromaffin cell vesicles
      and liposomes.
AB  - The mechanism of mammalian vesicle rupture onto the surface of a polarized carbon
      fiber microelectrode during electrochemical vesicle cytometry is investigated. It
      appears that following adsorption to the surface of the polarized electrode,
      electroporation leads to the formation of a pore at the interface between a
      vesicle and the electrode and this is shown to be potential dependent. The
      chemical cargo is then released through this pore to be oxidized at the electrode
      surface. This makes it possible to quantify the contents as it restricts
      diffusion away from the electrode and coulometric oxidation takes place. Using a
      bottom up approach, lipid-only transmitter-loaded liposomes were used to mimic
      native vesicles and the rupture events occurred much faster in comparison with
      native vesicles. Liposomes with added peptide in the membrane result in rupture
      events with a lower duration than that of liposomes and faster in comparison to
      native vesicles. Diffusional models have been developed and suggest that the
      trend in pore size is dependent on soft nanoparticle size and diffusion of the
      content in the nanometer vesicle. In addition, it appears that proteins form a
      barrier for the membrane to reach the electrode and need to move out of the way
      to allow close contact and electroporation. The protein dense core in vesicles
      matrixes is also important in the dynamics of the events in that it significantly
      slows diffusion through the vesicle.

PMID- 27711874
TI  - Gold nanoparticles supported by imidazolium-based porous organic polymers for
      nitroarene reduction.
AB  - Two imidazolium-based porous organic polymers (Im-POP-1 and Im-POP-2) were
      synthesized through the Yamamoto reaction of different molar ratios of 1,3-bis(4
      bromophenyl)imidazolium bromide and tetrakis(4-bromophenyl)methane, subsequent
      anion exchange with HAuCl4 and reduction with NaBH4 produced well-dispersed gold
      nanoparticles (NPs), Au@Im-POP-1 and Au@Im-POP-2. These NPs possess a small size
      and narrow size distribution, their application in the reduction of nitroarenes
      was evaluated, and the reduction process was tracked by 13C NMR experiments for
      reaction mechanism studies. In comparison with gold NPs supported by a non-ionic
      analogue from the Yamamoto reaction of tetrakis(4-bromophenyl)methane (Au@POP
      TPM), Au@Im-POP-2 exhibits high catalytic activity, good selectivity of aniline
      and superior recyclability in nitrobenzene reduction. The gold NPs in Au@Im-POP-2
      increase slightly after four consecutive reaction runs, while an apparent
      agglomeration of NPs in Au@POP-TPM was observed after the second run. This
      research provides a new type of support for the stabilization of gold NPs and for
      the improvement of catalytic performances.

PMID- 27711875
TI  - Classical to quantum mechanical tunneling mechanism crossover in thermal
      transitions between magnetic states.
AB  - Transitions between states of a magnetic system can occur by jumps over an energy
      barrier or by quantum mechanical tunneling through the energy barrier. The rate
      of such transitions is an important consideration when the stability of magnetic
      states is assessed for example for nanoscale candidates for data storage devices.
      The shift in transition mechanism from jumps to tunneling as the temperature is
      lowered is analyzed and a general expression derived for the crossover
      temperature. The jump rate is evaluated using a harmonic approximation to
      transition state theory. First, the minimum energy path for the transition is
      found with the geodesic nudged elastic band method. The activation energy for the
      jumps is obtained from the maximum along the path, a saddle point on the energy
      surface, and the eigenvalues of the Hessian matrix at that point as well as at
      the initial state minimum used to estimate the entropic pre-exponential factor.
      The crossover temperature for quantum mechanical tunneling is evaluated from the
      second derivatives of the energy with respect to orientation of the spin vector
      at the saddle point. The resulting expression is applied to test problems where
      analytical results have previously been derived, namely uniaxial and biaxial spin
      systems with two-fold anisotropy. The effect of adding four-fold anisotropy on
      the crossover temperature is demonstrated. Calculations of the jump rate and
      crossover temperature for tunneling are also made for a molecular magnet
      containing an Mn4 group. The results are in excellent agreement with previously
      reported experimental measurements on this system.

PMID- 27711876
TI  - Evaluation of bis-cyclometalated alkynylgold(iii) sensitizers for water
      photoreduction to hydrogen.
AB  - Well-defined gold sensitizers for hydrogen production from water remain extremely
      rare despite decades of interest, and are currently limited to systems based on
      ruthenium, iridium or platinum complexes. This report details the synthesis and
      characterization of a series of neutral cyclometalated gold(iii) complexes of the
      type [(RC^N^CR)Au(C[triple bond, length as m-dash]C-R')] (R = H or tert-butyl
      group; R' = aryl groups) that have been found to be good candidates to function
      as harvesting materials in light-induced electron transfer reactions. We
      established the efficacy of systems with these gold(iii) complexes as
      photosensitizers (PSs) in the production of renewable hydrogen in the presence of
      [Co(2,2'-bipyridine)3]Cl2 or [Rh(4,4'-di-tert-butyl-2,2'-bipyridine)3](PF6)3 as a
      H2-evolved catalyst and triethanolamine (TEOA) as a sacrificial electron donor in
      acetone-water solution. All complexes are active, and there is a more than
      threefold increase over other candidates in photocatalytic H2 generation
      activity. Under the optimal reaction conditions, hydrogen evolution took place
      through a photochemical route with the highest efficiency and with a turnover
      number (TON) of up to 1441.5 relative to the sensitizer over 24 hours. In the
      initial photochemical path, the reductive quenching of the excited gold(iii)
      complex by TEOA due to the latter's greater concentration in the system followed
      by electron transfer to the catalyst species is proposed to be the dominant
      mechanism. A photo-to-H2 quantum yield of approximately 13.7% was attained when
      illuminated with monochromatic light of 400 nm. Such gold(iii) complexes have
      demonstrated significant utility in solar-to-hydrogen reactions and thus
      represent a new effective class of light-harvesting materials. These results open
      possibilities for pursuing more efficient photosensitizers featuring gold(iii)
      complexes in photocatalytic solar energy conversion.

PMID- 27711877
TI  - Rare-earth metal diisopropylamide-catalyzed intramolecular hydroamination.
AB  - Rare-earth metal diisopropylamide complexes LiLn(NiPr2)4(THF) (Ln = Sc, Y, La),
      [LiY(NiPr2)4]n, NaLn(NiPr2)4(THF) (Ln = Sc, Y), Sc(NiPr2)3(THF) and Ce(NiPr2)4
      were screened as catalysts for the intramolecular hydroamination/cyclization
      (IHC) of 1-amino-2,2-dimethyl-4-pentene, 1-amino-2,2-diphenyl-4-pentene, and 1
      amino-2,2-diphenyl-5-hexene at ambient and moderately increased temperature of 60
      degrees C in C6D6. The lithium ate complexes displayed the most efficient
      precatalysts with high conversion rates at 60  degrees C for the phenyl
      substituted substrates and Ln = Y and La, affording turnover frequencies Nt as
      high as 164 h-1. The catalytic activity could be increased by employing THF-free
      complex [LiY(NiPr2)4]n (Nt = 45.8 h-1 at 26  degrees C; 34.1 h-1 for
      LiY(NiPr2)4(THF)). In situ generation of putative LiY(NiPr2)4(THF) from
      YCl3(THF)3.3 and four equivalents of LiNiPr2 (LDA) in C6D6 generated a catalyst
      revealing Nt comparable to pre-isolated crystallized LiY(NiPr2)4(THF) but
      yielding even higher substrate conversion. The IHC reactions were also examined
      for rare-earth metal bis(trimethylsilyl)amide catalysts Ln[N(SiMe3)2]3 (Ln = Sc,
      Y, La) as well as for LDA using the same reaction conditions, revealing overall
      superior activity of the silylamide derivatives but poor performance of LDA
      compared to the rare-earth metal diisopropylamide complexes LiLn(NiPr2)4(THF).
      Cyclization of 1-amino-2,2-diphenyl-5-hexene to the 6-membered heterocycle 2
      methyl-4,4-diphenylpiperidine by lanthanum derivative LiLa(NiPr2)4(THF) was
      accompanied by a competitive isomerization reaction affording max. 20% of 1-amino
      2,2-diphenyl-4-hexene after 2 h at 60  degrees C. Crystalline tetravalent
      Ce(NiPr2)4 showed a better IHC performance than crystalline trivalent
      Sc(NiPr2)3(THF) as preliminary examined for 1-amino-2,2-diphenyl-4-pentene at 26 
      degrees C (Nt = 5.6 and 0.9 h-1, respectively), but cyclization came to a halt
      after 2 h, probably due to decomposition of the catalyst.

PMID- 27711878
TI  - Correction: The biology of environmental stress: molecular biomarkers in Sydney
      rock oysters (Saccostrea glomerata).
AB  - Correction for 'The biology of environmental stress: molecular biomarkers in
      Sydney rock oysters (Saccostrea glomerata)' by D. A. Raftos et al., Environ.
      Sci.: Processes Impacts, 2016, 18, 1129-1139.

PMID- 27711879
TI  - Synthesis and molecular structure of a spheroidal binary nanoscale copper sulfide
      cluster.
AB  - The reaction of copper(4-(tert-butyl)phenyl)methanethiolate [CuSCH2C6H4tBu] with
      bis(trimethylsilyl)sulfide S(SiMe3)2 in the presence of triphenylphosphine PPh3
      afforded the binary 52 nuclear copper cluster [Cu52S12(SCH2C6H4tBu)28(PPh3)8].
      The molecular structure of this intensely red coloured nanoscale Cu2S mimic was
      established by single crystal X-ray diffraction.

PMID- 27711880
TI  - Facile preparation of NiCo2O4@rGO composites for the removal of uranium ions from
      aqueous solutions.
AB  - A hierarchical structure of NiCo2O4@rGO composite has been fabricated, with its
      structure and morphology well characterized by XRD, TEM, XPS and BET. The results
      proved that the NiCo2O4 nanosheets grow uniformly on both sides of the graphene
      sheets. In batch adsorption experiments, the effects of equilibrium time, pH and
      temperature on uranium(vi) adsorption were investigated. The main results show
      that the NiCo2O4@rGO composite has a higher affinity towards the uptake of
      uranium(vi) from aqueous solutions. The highest adsorption capacity reached 342.4
      mg U g-1 at pH 5.0. Kinetic analysis shows that the adsorption process is
      described best by a pseudo-second-order kinetic model. The uranium(vi) sorption
      equilibrium data correlates well with the Langmuir sorption isotherm model in the
      thermodynamic analysis. Thus, NiCo2O4@rGO composite is an excellent adsorbent for
      removing uranium(vi) ions.

PMID- 27711881
TI  - Structural dynamics of photochemical reactions probed by time-resolved
      photoelectron spectroscopy using high harmonic pulses.
AB  - Femtosecond ring-opening dynamics of 1,3-cyclohexadiene (CHD) in gas phase upon
      two-photon excitation at 400 nm (=3.1 eV) was investigated by time-resolved
      photoelectron spectroscopy using 42 nm (=29.5 eV) high harmonic photons probing
      the dynamics of the lower-lying occupied molecular orbitals (MOs), which are the
      fingerprints of the molecular structure. After 500 fs, the photoelectron
      intensity of the MO constituting the C[double bond, length as m-dash]C sigma bond
      (sigmaC[double bond, length as m-dash]C) of CHD was enhanced, while that of the
      MO forming the C-C sigma bond (sigmaCC) of CHD was decreased. The changes in the
      photoelectron spectra suggest that the ring of CHD opens to form a 1,3,5
      hexatriene (HT) after 500 fs. The dynamics of the sigmaC[double bond, length as m
      dash]C and sigmaCC bands between 200 and 500 fs reflects the ring deformation to
      a conical intersection between the 21A and 11A potential energy surfaces prior to
      the ring-opening reaction.

PMID- 27711882
TI  - Crystal structure, thermal expansion and electrical conductivity of
      LaCoxNiyMozO3.
AB  - The effect of Mo-substitution was investigated for the LaCoxNiyMozO3 system,
      obtaining single-phase perovskite for Mo-substitutions up to 20 at%. The crystal
      structure of the perovskite changed from rhombohedral, orthorhombic to monoclinic
      with increasing Mo-content. The thermal expansion was suppressed by Mo
      substitution, while the electrical conductivity was also suppressed, but remained
      relatively high.

PMID- 27711883
TI  - Deterministic modeling of the exposure of individual participants in the National
      Health and Nutrition Examination Survey (NHANES) to polychlorinated biphenyls.
AB  - A population's exposure to persistent organic pollutants, e.g., polychlorinated
      biphenyls (PCBs), is typically assessed through national biomonitoring programs,
      such as the United States National Health and Nutrition Examination Survey
      (NHANES). To complement statistical methods, we use a deterministic modeling
      approach to establish mechanistic links between human contaminant concentrations
      and factors (e.g. age, diet, lipid mass) deemed responsible for the often
      considerable variability in these concentrations. Lifetime exposures to four PCB
      congeners in 6128 participants from NHANES 1999-2004 are simulated using the ACC
      Human model supplied with individualized input parameters obtained from NHANES
      questionnaires (e.g., birth year, sex, body mass index, dietary composition,
      reproductive behavior). Modeled and measured geometric mean PCB-153
      concentrations in NHANES participants of 13.3 and 22.0 ng g-1 lipid,
      respectively, agree remarkably well, although lower model-measurement agreement
      for air, water, and food suggests that this is partially due to fortuitous error
      cancellation. The model also reproduces trends in the measured data with key
      factors such as age, parity and sex. On an individual level, 62% of all modeled
      concentrations are within a factor of three of their corresponding measured
      values (Spearman rs = 0.44). However, the model attributes more of the inter
      individual variability to differences in dietary lipid intake than is indicated
      by the measured data. While the model succeeds in predicting levels and trends on
      the population level, the accuracy of individual-specific predictions would need
      to be improved for refined exposure characterization in epidemiological studies.

PMID- 27711884
TI  - Imaging electrocatalytic processes on single gold nanorods.
AB  - Imaging electrochemical processes has attracted increasing attention in past
      decades. Particularly, monitoring electrochemical reactions rapidly at the nano
      scale is still a challenge due to the ultra-low current detection and long
      scanning time required. The development of optical techniques provide a new way
      to demonstrate electrochemical processes through optical signals which enhance
      sensitivity and spatial resolution. Herein, we developed a novel method to image
      electrocatalytic processes on single gold nanorods (GNRs) during Cyclic
      Voltammetry (CV) scanning based on plasmon resonance scattering information by
      using dark-field microscopy. The electrocatalytic oxidation of hydrogen peroxide
      was selected as a typical reaction and the catalytic mechanism was revealed using
      the obtained spectra. Notably, observation on single GNRs avoided the averaging
      effects in bulk systems and confirmed that the individual nanoparticles had
      variable catalytic properties with different spectral change during the reaction
      process. Furthermore, a color-amplified system was introduced to convert light
      intensity into imaging information via the Matlab program which was able to image
      thousands of nanoparticles simultaneously. This approach offered the statistical
      intensity distribution of all of the nanoparticles in a dark-field image which
      dramatically enhanced the detection accuracy and avoided random events.

PMID- 27711885
TI  - A passive dosing method to determine fugacity capacities and partitioning
      properties of leaves.
AB  - The capacity of leaves to take up chemicals from the atmosphere and water
      influences how contaminants are transferred into food webs and soil. We provide a
      proof of concept of a passive dosing method to measure leaf/polydimethylsiloxane
      partition ratios (Kleaf/PDMS) for intact leaves, using polychlorinated biphenyls
      (PCBs) as model chemicals. Rhododendron leaves held in contact with PCB-loaded
      PDMS reached between 76 and 99% of equilibrium within 4 days for PCBs 3, 4, 28,
      52, 101, 118, 138 and 180. Equilibrium Kleaf/PDMS extrapolated from the uptake
      kinetics measured over 4 days ranged from 0.075 (PCB 180) to 0.371 (PCB 3). The
      Kleaf/PDMS data can readily be converted to fugacity capacities of leaves (Zleaf)
      and subsequently leaf/water or leaf/air partition ratios (Kleaf/water and
      Kleaf/air) using partitioning data from the literature. Results of our
      measurements are within the variability observed for plant/air partition ratios
      (Kplant/air) found in the literature. Log Kleaf/air from this study ranged from
      5.00 (PCB 3) to 8.30 (PCB 180) compared to log Kplant/air of 3.31 (PCB 3) to 8.88
      (PCB 180) found in the literature. The method we describe could provide data to
      characterize the variability in sorptive capacities of leaves that would improve
      descriptions of uptake of chemicals by leaves in multimedia fate models.

PMID- 27711886
TI  - Review of chemical and electrokinetic remediation of PCBs contaminated soils and
      sediments.
AB  - Polychlorinated biphenyls (PCBs) are manmade organic compounds, and pollution due
      to PCBs has been a global environmental problem because of their persistence,
      long-range atmospheric transport and bioaccumulation. Many physical, chemical and
      biological technologies have been utilized to remediate PCBs contaminated soils
      and sediments, and there are some emerging new technologies and combined methods
      that may provide cost-effective alternatives to the existing remediation
      practice. This review provides a general overview on the recent developments in
      chemical treatment and electrokinetic remediation (EK) technologies related to
      PCBs remediation. In particular, four technologies including photocatalytic
      degradation of PCBs combined with soil washing, Fe-based reductive
      dechlorination, advanced oxidation process, and EK/integrated EK technology
      (e.g., EK coupled with chemical oxidation, nanotechnology and bioremediation) are
      reviewed in detail. We focus on the fundamental principles and governing factors
      of chemical technologies, and EK/integrated EK technologies. Comparative analysis
      of these technologies including their major advantages and disadvantages is
      summarized. The existing problems and future prospects of these technologies
      regarding PCBs remediation are further highlighted.

PMID- 27711887
TI  - High-bandwidth detection of short DNA in nanopipettes.
AB  - Glass or quartz nanopipettes have found increasing use as tools for studying the
      biophysical properties of DNA and proteins, and as sensor devices. The ease of
      fabrication, favourable wetting properties and low capacitance are some of the
      inherent advantages, for example compared to more conventional, silicon-based
      nanopore chips. Recently, we have demonstrated high-bandwidth detection of double
      stranded (ds) DNA with microsecond time resolution in nanopipettes, using custom
      designed electronics. The electronics design has now been refined to include more
      sophisticated control features, such as integrated bias reversal and other
      features. Here, we exploit these capabilities and probe the translocation of
      short dsDNA in the 100 bp range, in different electrolytes. Single-stranded (ss)
      DNA of similar length are in use as capture probes, so label-free detection of
      their ds counterparts could therefore be of relevance in disease diagnostics.

PMID- 27711889
TI  - Probing the excited state relaxation dynamics of pyrimidine nucleosides in
      chloroform solution.
AB  - Ultrafast transient electronic and vibrational absorption spectroscopy (TEAS and
      TVAS) of 2'-deoxy-cytidine (dC) and 2'-deoxy-thymidine (dT) dissolved in
      chloroform examines their excited-state dynamics and the recovery of ground
      electronic state molecules following absorption of ultraviolet light. The
      chloroform serves as a weakly interacting solvent, allowing comparisons to be
      drawn with prior experimental studies of the photodynamics of these nucleosides
      in the gas phase and in polar solvents such as water. The pyrimidine base
      nucleosides have some propensity to dimerize in aprotic solvents, but the monomer
      photochemistry can be resolved clearly and is the focus of this study. UV
      absorption at a wavelength of 260 nm excites a 1pipi* <- S0 transition, but
      prompt crossing of a significant fraction (50% in dC, 17% in dT) of the 1pipi*
      population into a nearby 1npi* state is too fast for the experiments to resolve.
      The remaining flux on the 1pipi* state leaves the vertical Franck-Condon region
      and encounters a conical intersection with the ground electronic state of
      ethylenic twist character. In dC, the 1pipi* state decays to the ground state
      with a time constant of 1.1 +/- 0.1 ps. The lifetime of the 1npi* state is much
      longer in the canonical forms of both molecules: recovery of the ground state
      population from these states occurs with time constants of 18.6 +/- 1.1 ps in
      amino-oxo dC and ~114 ps in dT, indicating potential energy barriers to the
      1npi*/S0 conical intersections. The small fraction of the imino-oxo tautomer of
      dC present in solution has a longer-lived 1npi* state with a lifetime for ground
      state recovery of 193 +/- 55 ps. No evidence is found for photo-induced
      tautomerization of amino-oxo dC to the imino-oxo form, or for population of low
      lying triplet states of this nucleoside. In contrast, ~8% of the UV-excited dT
      molecules access the long-lived T1 (3pipi*) state through the 1npi* state. The
      primary influence of the solvent appears to be the degree to which it
      destabilizes the states of 1npi* character, with consequences for the lifetimes
      of these states as well as the triplet state yields.

PMID- 27711888
TI  - Energetics of base flipping at a DNA mismatch site confined at the latch
      constriction of alpha-hemolysin.
AB  - Unique, two-state modulating current signatures are observed when a cytosine
      cytosine mismatch pair is confined at the 2.4 nm latch constriction of the alpha
      hemolysin (alphaHL) nanopore. We have previously speculated that the modulation
      is due to base flipping at the mismatch site. Base flipping is a biologically
      significant mechanism in which a single base is rotated out of the DNA helical
      stack by 180 degrees . It is the mechanism by which enzymes are able to access
      bases for repair operations without disturbing the global structure of the helix.
      Here, temperature dependent ion channel recordings of individual double-stranded
      DNA duplexes inside alphaHL are used to derive thermodynamic (DeltaH, DeltaS) and
      kinetic (EA) parameters for base flipping of a cytosine at an unstable cytosine
      cytosine mismatch site. The measured activation energy for flipping a cytosine
      located at the latch of alphaHL out of the helix (18 +/- 1 kcal mol-1) is
      comparable to that previously reported for base flipping at mismatch sites from
      NMR measurements and potential mean force calculations. We propose that the
      alphaHL nanopore is a useful tool for measuring conformational changes in dsDNA
      at the single molecule level.

PMID- 27711890
TI  - Applications: general discussion.

PMID- 27711891
TI  - Transformation of mackinawite to greigite by trichloroethylene and
      tetrachloroethylene.
AB  - Trichloroethylene (TCE) and tetrachloroethylene (PCE) are common ground water
      contaminants susceptible to reductive dechlorination by FeS (mackinawite) in
      anaerobic environments. The objective of this study was to characterize the
      mineral-associated products that form when mackinawite reacts with TCE and PCE.
      The dissolved products of the reaction included Cl- and Fe2+, and trace amounts
      of cis 1,2-dichloroethylene (for TCE) and TCE (for PCE). Selected area electron
      diffraction (SAED) analysis identified greigite as a mackinawite oxidation
      product formed after reaction between TCE or PCE and FeS over seven weeks.
      Release of Fe2+ is consistent with the solid state transformation of mackinawite
      to greigite, resulting in depletion of the solid with Fe. X-ray photoelectron
      spectroscopy of the sulfur 2p peak showed a shift to a higher binding energy
      after FeS reacted with TCE or PCE, also observed in other studies of mackinawite
      oxidation to greigite. The results may help efforts to maintain the reactivity of
      FeS generated to remediate chlorinated aliphatic contaminants in ground water.

PMID- 27711892
TI  - Electrochemical transformation of individual nanoparticles revealed by coupling
      microscopy and spectroscopy.
AB  - Although extremely sensitive, electrical measurements are essentially unable to
      discriminate complex chemical events involving individual nanoparticles. The
      coupling of electrochemistry to dark field imaging and spectroscopy allows the
      triggering of the electrodissolution of an ensemble of Ag nanoparticles (by
      electrochemistry) and the inference of both oxidation and dissolution processes
      (by spectroscopy) at the level of a single nanoparticle. Besides the inspection
      of the dissolution process from optical scattering intensity, adding optical
      spectroscopy reveals chemical changes through drastic spectral changes. The
      behaviours of single NPs and NP agglomerates are differentiated: in the presence
      of thiocyanate ions, the transformation of Ag single nanoparticles to AgSCN is
      investigated in the context of plasmonic coupling with the electrode; tentative
      interpretations for optically unresolved groups of nanoparticles are proposed.

PMID- 27711893
TI  - Single molecular catalysis of a redox enzyme on nanoelectrodes.
AB  - Due to a high turnover coefficient, redox enzymes can serve as current amplifiers
      which make it possible to explore their catalytic mechanism by electrochemistry
      at the level of single molecules. On modified nanoelectrodes, the voltammetric
      behavior of a horseradish peroxidase (HRP) catalyzed hydroperoxide reduction no
      longer presents a continuous current response, but a staircase current response.
      Furthermore, single catalytic incidents were captured through a collision mode at
      a constant potential, from which the turnover number of HRP can be figured out
      statistically. In addition, the catalytic behavior is dynamic which may be caused
      by the orientation status of HRP on the surface of the electrode. This modified
      nanoelectrode methodology provides an electrochemical approach to investigate the
      single-molecule catalysis of redox enzymes.

PMID- 27711894
TI  - Nanocapillary electrokinetic tracking for monitoring charge fluctuations on a
      single nanoparticle.
AB  - We introduce nanoCapillary Electrokinetic Tracking (nanoCET), an optofluidic
      platform for continuously measuring the electrophoretic mobility of a single
      colloidal nanoparticle or macromolecule in vitro with millisecond time resolution
      and high charge sensitivity. This platform is based on using a nanocapillary
      optical fiber in which liquids may flow inside a channel embedded inside the
      light-guiding core and nanoparticles are tracked using elastic light scattering.
      Using this platform we have experimentally measured the electrophoretic mobility
      of 60 nm gold nanoparticles in an aqueous environment. Further, using numerical
      simulations, we demonstrate the underlying electrokinetic dynamics inside the
      nanocapillary and the necessary steps for extending this method to probing single
      biomolecules, which can be achieved with existing technologies. This achievement
      will immensely facilitate the daunting challenge of monitoring biochemical or
      catalytic reactions on a single entity over a wide range of timescales. The
      unique measurement capabilities of this platform pave the way for a wide range of
      discoveries in colloid science, analytical biochemistry, and medical diagnostics.

PMID- 27711895
TI  - Confronting surface hopping molecular dynamics with Marcus theory for a molecular
      donor-acceptor system.
AB  - We investigate the performance of fewest switches surface hopping (SH) in
      describing electron transfer (ET) for a molecular donor-acceptor system. Computer
      simulations are carried out for a wide range of reorganisation energy (lambda),
      electronic coupling strength (Hab) and driving force using our recently developed
      fragment orbital-based SH approach augmented with a simple decoherence
      correction. This methodology allows us to compute SH ET rates over more than four
      orders of magnitude, from the sub-picosecond to the nanosecond time regime. We
      find good agreement with semi-classical ET theory in the non-adiabatic ET regime.
      The correct scaling of the SH ET rate with electronic coupling strength is
      obtained and the Marcus inverted regime is reproduced, in line with previously
      reported results for a spin-boson model. Yet, we find that the SH ET rate falls
      below the semi-classical ET rate in the adiabatic regime, where the free energy
      barrier is in the order of kBT in our simulations. We explain this by first
      signatures of non-exponential population decay of the initial charge state. For
      even larger electronic couplings (Hab = lambda/2), the free energy barrier
      vanishes and ET rates are no longer defined. At this point we observe a crossover
      from ET on the vibronic time scale to charge relaxation on the femtosecond time
      scale that is well described by thermally averaged Rabi oscillations. The
      extension of the analysis from the non-adiabatic limit to large electronic
      couplings and small or even vanishing activation barriers is relevant for our
      understanding of charge transport in organic semiconductors.

PMID- 27711896
TI  - Electrochemistry at single molecule occupancy in nanopore-confined recessed ring
      disk electrode arrays.
AB  - Electrochemical reactions at nanoscale structures possess unique characteristics,
      e.g. fast mass transport, high signal-to-noise ratio at low concentration, and
      insignificant ohmic losses even at low electrolyte concentrations. These
      properties motivate the fabrication of high density, laterally ordered arrays of
      nanopores, embedding vertically stacked metal-insulator-metal electrode
      structures and exhibiting precisely controlled pore size and interpore spacing
      for use in redox cycling. These nanoscale recessed ring-disk electrode (RRDE)
      arrays exhibit current amplification factors, AFRC, as large as 55-fold with
      Ru(NH3)62/3+, indicative of capture efficiencies at the top and bottom
      electrodes, Phit,b, exceeding 99%. Finite element simulations performed to
      investigate the concentration distribution of redox species and to assess
      operating characteristics are in excellent agreement with experiment. AFRC
      increases as the pore diameter, at constant pore spacing, increases in the range
      200-500 nm and as the pore spacing, at constant pore diameter, decreases in the
      range 1000-460 nm. Optimized nanoscale RRDE arrays exhibit a linear current
      response with concentration ranging from 0.1 MUM to 10 mM and a small capacitive
      current with scan rate up to 100 V s-1. At the lowest concentrations, the average
      pore occupancy is <n> ~ 0.13 molecule establishing productive electrochemical
      signals at occupancies at and below the single molecule level in these nanoscale
      RRDE arrays.

PMID- 27711897
TI  - Janus and patchy nanoparticles: general discussion.

PMID- 27711899
TI  - Stimulated X-ray Raman scattering - a critical assessment of the building block
      of nonlinear X-ray spectroscopy.
AB  - With the invention of femtosecond X-ray free-electron lasers (XFELs), studies of
      light-induced chemical reaction dynamics and structural dynamics reach a new era,
      allowing for time-resolved X-ray diffraction and spectroscopy. To ultimately
      probe coherent electron and nuclear dynamics on their natural time and length
      scales, coherent nonlinear X-ray spectroscopy schemes have been proposed. In this
      contribution, we want to critically assess the experimental realisation of
      nonlinear X-ray spectroscopy at current-day XFEL sources, by presenting first
      experimental attempts to demonstrate stimulated resonant X-ray Raman scattering
      in molecular gas targets.

PMID- 27711900
TI  - Stochastic electrochemistry and photoelectrochemistry of colloidal dye-sensitized
      anatase nanoparticles at a Pt ultramicroelectrode.
AB  - We report the stochastic interactions between dye sensitized anatase
      nanoparticles, suspended in a colloid, and a Pt ultramicroelectrode (UME) that
      result in step-wise behavior in the current vs. time response. The stochastic
      currents are observed in the dark and under illumination. In the dark, the
      currents are anodic, consistent with the oxidation of the dye N719 at the Pt
      surface. The electrochemical behavior of the dye was investigated in MeOH and
      MeCN with a quasireversible cyclic voltammogram (CV) observed at 1 V s-1. The
      anodic currents observed in the dark due to nanoparticles (NPs) at the Pt surface
      are consistent with the CVs in MeOH and MeCN. Under illumination cathodic steps
      are observed and assigned to the reduction of the oxidized form of the dye
      generated after electrons are injected into the TiO2 NPs. The colloidal behavior
      is a strong function of the history of the colloid with illumination time
      increasing the size of the agglomerates and with larger agglomerates being less
      photoelectrochemically active. Agglomerates of ca. 100 nm in diameter are
      proposed to be photoactive entities with a higher probability of detection that
      contribute to the staircase photocurrent response.

PMID- 27711898
TI  - Imaging ultrafast excited state pathways in transition metal complexes by X-ray
      transient absorption and scattering using X-ray free electron laser source.
AB  - This report will describe our recent studies of transition metal complex
      structural dynamics on the fs and ps time scales using an X-ray free electron
      laser source, Linac Coherent Light Source (LCLS). Ultrafast XANES spectra at the
      Ni K-edge of nickel(ii) tetramesitylporphyrin (NiTMP) were measured for optically
      excited states at a timescale from 100 fs to 50 ps, providing insight into its
      sub-ps electronic and structural relaxation processes. Importantly, a transient
      reduced state Ni(i) (pi, 3dx2-y2) electronic state is captured through the
      interpretation of a short-lived excited state absorption on the low-energy
      shoulder of the edge, which is aided by the computation of X-ray transitions for
      postulated excited electronic states. The observed and computed inner shell to
      valence orbital transition energies demonstrate and quantify the influence of the
      electronic configuration on specific metal orbital energies. A strong influence
      of the valence orbital occupation on the inner shell orbital energies indicates
      that one should not use the transition energy from 1s to other orbitals to draw
      conclusions about the d-orbital energies. For photocatalysis, a transient
      electronic configuration could influence d-orbital energies up to a few eV and
      any attempt to steer the reaction pathway should account for this to ensure that
      external energies can be used optimally in driving desirable processes. NiTMP
      structural evolution and the influence of the porphyrin macrocycle conformation
      on relaxation kinetics can be likewise inferred from this study.

PMID- 27711902
TI  - Challenges in nanoelectrochemical and nanomechanical studies of individual
      anisotropic gold nanoparticles.
AB  - The characterization of nanoparticles and the correlation of physical properties
      such as size and shape to their (electro)chemical properties is an emerging
      field, which may facilitate future optimization and tuning of devices involving
      nanoparticles. This requires the investigation of individual particles rather
      than obtaining averaged information on large ensembles. Here, we present atomic
      force - scanning electrochemical microscopy (AFM-SECM) measurements of soft
      conductive PDMS substrates modified with gold nanostars (i.e., multibranched Au
      nanoparticles) in peak force tapping mode, which next to the electrochemical
      characterization provides information on the adhesion, deformation properties,
      and Young's modulus of the sample. AFM-SECM probes with integrated nanodisc
      electrodes (radii < 50 nm) have been used for these measurements. Most studies
      attempting to map individual nanoparticles have to date been performed at
      spherical nanoparticles, rather than highly active asymmetric gold nanoparticles.
      Consequently, this study discusses challenges during the nanocharacterization of
      individual anisotropic gold nanostars.

PMID- 27711901
TI  - Goat sausages containing chitosan towards a healthier product: microbiological,
      physico-chemical textural evaluation.
AB  - Goat meat is extensively known for its interesting nutritional value and for
      being an important source of protein with high quality. Its food derivatives are,
      therefore, a good alternative to develop new products addressed to health
      conscious consumers. In this work, a healthier goat product, namely, a low fat
      fresh sausage, was produced with the objective of evaluating the effect of
      inclusion of chitosan on quality, stability and shelf life. Sausages containing
      2% chitosan were formulated with different fat levels (5%, 12.5% and 20%, w/w)
      and stored at 4  degrees C for 15 days. Results indicated the incorporation of 2%
      (w/w) chitosan was technologically feasible, due to the reduction of microbial
      growth and lipid oxidation, as well as the enhancement of red color.
      Additionally, the treated samples improved all the characteristics associated
      with cooking, showing the ability to bind water and fat and acquiring a firmer
      texture compared with control samples. Additionally, the reduction of fat content
      is technologically feasible without negative influences on the final product.

PMID- 27711903
TI  - Quantification of microbial uptake of quercetin and its derivatives using an
      UHPLC-ESI-QTOF mass spectrometry assay.
AB  - A liquid chromatography-mass spectrometry-based method for the quantification of
      intracellular concentrations of dietary phenolics in bacteria was developed.
      Using this assay, the time-dependent uptake of quercetin and two of its
      glycosides into gut microbiota model organisms (Escherichia coli and
      Bifidobacterium bifidum) under aerobic and anaerobic conditions was studied. For
      the first time, quantitative data on the uptake of dietary phenols were obtained
      indicating a time-dependent differential uptake of the dietary compounds. The
      shape of the uptake curve and the comparative use of bacterial mutants lacking
      porins OmpFC or the multi-drug efflux pump AcrAB, respectively, along with the
      identification and quantification of selected bacterial metabolites provided a
      mechanistic insight into the uptake process.

PMID- 27711904
TI  - Anisotropic nanoparticles: general discussion.

PMID- 27711905
TI  - Particles at interfaces: general discussion.

PMID- 27711906
TI  - Proteomic response of inflammatory stimulated intestinal epithelial cells to in
      vitro digested plums and cabbages rich in carotenoids and polyphenols.
AB  - Due to their anti-oxidant and anti-inflammatory potential, polyphenol and
      carotenoid-rich plant foods have been suggested as promising phytochemicals in
      the prevention of or as adjuvants regarding inflammatory bowel diseases (IBD). In
      the present study, we investigated whether plum (Italian Plum, Prunus cocomilla),
      or cabbage (Kale, Brassica oleracea var. sabellica), selected for their high
      phytochemical content, are able to reduce inflammation in cellular models of the
      intestinal epithelium, employing proteomic methods. For this purpose,
      plum/cabbage (carotenoid content: 1.9 mg per 100 g resp. 13 mg per 100 g;
      polyphenol content: 83 mg per 100 g resp. 27 mg per 100 g) were gastro
      intestinally digested, and aliquots exposed (18 h) to either a monoculture (Caco
      2) or a triple culture (Caco-2/HT-29-MTX (90 : 10, v/v) with THP-1 like
      macrophages), stimulated (with LPS, TNF-alpha, and IL-1beta) to induce
      inflammation. Cells (Caco-2, Caco-2/HT-29-MTX, and THP-1) were then harvested
      separately, and proteomic analyses of total cell extracts were carried out by 2D
      DIGE. In the monoculture, 68 protein-spots were significantly (p < 0.05,
      expression ratio >1.5) differentially regulated due to the Kale and Italian plum
      digesta, and in the co-culture 206 protein-spots, compared to digesta without
      plum/cabbage. These belonged to 27 (monoculture) and 76 (coculture) uniquely
      identified proteins, suggesting the coculture to be a more sensitive model.
      Proteins included antioxidant enzymes such as catalase, superoxide dismutase and
      glutathione-S-transferases. Only 3 proteins were differentially regulated in the
      THP-1 cells, perhaps as these were only indirectly exposed. The results show
      promise regarding some aspects related to IBD complications, however, employing
      phytochemical-rich food items should be further investigated in in vivo trials.

PMID- 27711908
TI  - Membrane patches as ion channel probes for scanning ion conductance microscopy.
AB  - We describe dual-barrel ion channel probes (ICPs), which consist of an open
      barrel and a barrel with a membrane patch directly excised from a donor cell.
      When incorporated with scanning ion conductance microscopy (SICM), the open
      barrel (SICM barrel) serves to measure the distance-dependent ion current for non
      invasive imaging and positioning of the probe in the same fashion of traditional
      SICM. The second barrel with the membrane patch supports ion channels of interest
      and was used to investigate ion channel activities. To demonstrate robust probe
      control with the dual-barrel ICP-SICM probe and verify that the two barrels are
      independently addressable, current-distance characteristics (approach curves)
      were obtained with the SICM barrel and simultaneous, current-time (I-T) traces
      were recorded with the ICP barrel. To study the influence that the distance
      between ligand-gated ion channels (i.e., large conductance Ca2+-activated K+
      channels/BK channels) and the ligand source (i.e., Ca2+ source) has on channel
      activations, ion channel activities were recorded at two fixed probe-substrate
      distances (Dps) with the ICP barrel. The two fixed positions were determined from
      approach curves acquired with the SICM barrel. One position was defined as the
      "In-control" position, where the probe was in close proximity to the ligand
      source; the second position was defined as the "Far" position, where the probe
      was retracted far away from the ligand source. Our results confirm that channel
      activities increased dramatically with respect to both open channel probability
      and single channel current when the probe was near the ligand source, as opposed
      to when the probe was far away from the ligand source.

PMID- 27711907
TI  - Influence of the addition of Lactobacillus acidophilus La-05, Bifidobacterium
      animalis subsp. lactis Bb-12 and inulin on the technological, physicochemical,
      microbiological and sensory features of creamy goat cheese.
AB  - The effects of the addition of Lactobacillus acidophilus LA-05, Bifidobacterium
      animalis subsp. lactis BB-12 and inulin on the quality characteristics of creamy
      goat cheese during refrigerated storage were evaluated. The manufactured cheeses
      included the addition of starter culture (Lactococcus lactis subsp. lactis and
      Lactococcus lactis subsp. cremoris - R-704) (CC); starter culture, L. acidophilus
      LA-05 and inulin (CLA); starter culture, B. lactis BB-12 and inulin (CBB); or
      starter culture, L. acidophilus LA-05, B. lactis BB-12 and inulin (CLB). In the
      synbiotic cheeses (CLA, CBB and CLB), the counts of L. acidophilus LA-05 and B.
      lactis BB-12 were greater than 6log CFU g-1, the amount of inulin was greater
      than 6 g per 100 g, and the firmness was reduced. The cheeses evaluated had high
      brightness values (L*), with a predominance of yellow (b*). CC had higher
      contents of proteins, lipids and minerals compared to the other cheeses. There
      was a decrease in the amount of short-chain fatty acids (SCFAs) and an increase
      of medium-chain (MCFAs) and long-chain fatty acids (LCFAs) in the synbiotic
      cheeses compared to CC. The amount of conjugated linoleic acid increased in CLA,
      CBB and CLB. The highest depth of proteolysis and the greatest changes in the
      release of free amino acids were found in CLB. The addition of inulin and
      probiotics, alone or in co-culture, did not affect the cheese acceptance. Inulin
      and probiotics can be used together for the production of creamy goat cheese
      without negatively affecting the general quality characteristics of the product,
      and to add value because of its synbiotic potential.

PMID- 27711910
TI  - Long-term Adjuvant Tamoxifen Therapy and Decreases in Contralateral Breast
      Cancer.

PMID- 27711909
TI  - Reduced Levels of Tear Lacritin Are Associated With Corneal Neuropathy in
      Patients With the Ocular Component of Sjogren's Syndrome.
AB  - Purpose: To determine whether levels of endogenous tear protein, lacritin, are
      linked to altered corneal innervation and dry eye severity in patients with
      Sjogren's syndrome (SS). Methods: Clinical data were obtained from 10 SS and 10
      age-matched controls. Enzyme-linked immunosorbent assay was used to assess total
      tear lacritin extracted from Schirmer strips. Western blot was used to detect
      active lacritin monomer (~25 kDa), active lacritin fragment (~12-15 kDa), and
      inactive tissue transglutaminase-generated lacritin (>=40 kDa). In vivo confocal
      microscopy was used to assess nerve fiber density (NFD) and length (NFL).
      Relationships between nerve morphology and tear lacritin were examined by
      Spearman correlation. Diagnostic performance of tear lacritin was analyzed using
      receiver operating characteristic. Results: Active tear lacritin was
      significantly reduced in SS patients (3.72 +/- 5.62 [SS] versus 18.17 +/- 4.57
      ng/100 ng total tear protein [controls]; P < 0.001), while inactive lacritin was
      increased (84.99% +/- 11.15% [SS] versus 51.04% +/- 12.03% [controls]; P <
      0.001). Nerve fiber density (21.70 +/- 18.93 vs. 31.80 +/- 9.35; P = 0.03) and
      NFL (4.18 +/- 3.44 vs. 6.54 +/- 2.47; P < 0.05) were significantly decreased in
      SS patients compared to controls. Reduced NFL (r = 0.74, P < 0.01) and NFD (r =
      0.70, P < 0.01) were highly correlated with reduced tear lacritin. Similarly,
      total tear lacritin was highly correlated with Schirmers (r = 0.77, P < 0.01),
      ocular staining (r = -0.80, P < 0.01), and corneal sensitivity (r = 0.81, P <
      0.01). Tear lacritin showed equivalent or better diagnostic performance compared
      to traditional clinical measures for SS (100.00% sensitivity, 85.71% specificity,
      cutoff = 14.50 ng/100 ng tear protein). Conclusions: Reduced tear lacritin levels
      in SS patients are highly correlated with clinical signs of dry eye, as well as
      decreased NFD and NFL. Lacritin and its components provide excellent diagnostic
      sensitivity and specificity in SS.

PMID- 27711911
TI  - Full-Thickness Scalp Defects Reconstructed With Outer Table Calvarial
      Decortication and Surface Grafting.

PMID- 27711912
TI  - Association of Changes in Visual Acuity With Vision-Specific Functioning in the
      Singapore Malay Eye Study.
AB  - Importance: Longitudinal population-based data on the effect of vision loss on
      vision-specific functioning (VSF) are scarce, particularly in Asian populations.
      Objective: To examine the association between changes in presenting visual acuity
      (PVA) and VSF. Design, Setting, and Participants: Vision-specific functioning of
      1895 adults was assessed in the baseline (January 20, 2004-July 31, 2006) and
      follow-up (June 28, 2010-July 31, 2014) phases of the longitudinal population
      based Singapore Malay Eye Study. Mean (SD) differences and effect sizes for
      results of the modified Visual Function Index were calculated for 3 categories of
      change in PVA in the eye with better vision during the follow-up period (PVA gain
      of >=2 lines [+0.2 logMAR], no change [PVA between a loss of 2 lines and a gain
      of 2 lines], and PVA loss of >=2 lines [-0.2 logMAR]). The group with PVA loss
      was further stratified into incident vision impairment (VI) (baseline PVA >=6/12)
      and progression of VI (baseline PVA <6/12) that worsened by 2 or more lines at
      follow-up. Associations between PVA and VSF changes were assessed using multiple
      linear regression models. Exposures: Presenting visual acuity was measured using
      a logMAR chart during an ophthalmic examination at baseline and follow-up. Main
      Outcomes and Measures: Vision-specific functioning and associations between PVA
      and changes in VSF. Results: Of the 1895 participants (mean [SD] age at baseline,
      56.9 [10.1] years; 862 men and 1033 women), at follow-up, 319 (16.8%) had lost 2
      or more lines of PVA (mean [SD] PVA loss, 0.34 [0.22] logMAR; P < .001), which
      was associated with a mean (SD) -0.87 [2.12] logit decrease in VSF (medium effect
      size, -0.61). Of these 319 participants, 153 (48%) had incident VI and 166 (52%)
      had progression of VI, which were associated with mean (SD) -1.08 (2.15) (effect
      size, -0.86) and -0.64 (2.06) (effect size, -0.41) logit reductions in VSF,
      respectively. In adjusted models, compared with participants with no change in
      PVA, those who lost 2 or more lines had a significant 117% reduction in VSF
      (beta, -0.39; 95% CI, -0.62 to -0.16). Older age (-0.55 logit decrease in VSF;
      95% CI, -0.66 to -0.43) and female sex (-0.25 logit decrease in VSF; 95% CI, 
      0.45 to -0.06) were also independently associated with poorer VSF at follow-up (P
      < .01). Conclusions and Relevance: Approximately 1 in 6 Malay adults lost 2 or
      more lines of PVA during the 6 years of the study; this loss was associated with
      a sizable deterioration in VSF. Loss of VSF was greater in participants with new
      onset VI compared with those whose existing VI worsened. In older adults,
      strategies to prevent the onset of new VI may have more relative effect than
      delaying further progression among those with existing VI.

PMID- 27711913
TI  - Effect of Primary and Revision Repair on Palatal Motion.

PMID- 27711914
TI  - Second Malignant Neoplasms and Cause of Death in Patients With Germ Cell Cancer:
      A Danish Nationwide Cohort Study.
AB  - Importance: Patients given systemic treatment for testicular germ cell cancer
      (GCC) are at increased risk for a second malignant neoplasm (SMN). Previous
      studies on SMN and causes of death lacked information on the exact treatment
      applied or were based on patients receiving former treatment options. Objective:
      To evaluate the treatment-specific risks for SMN and death in a nationwide
      population-based cohort of patients with GCC treated with current standard
      regimens. Design, Setting, and Participants: This study examined a Danish
      nationwide cohort of 5190 men with GCC who entered the Danish Testicular Cancer
      database between January 1, 1984, and December 31, 2007. Treatment results were
      compared with a randomly sampled, age-stratified, population-based control group.
      Cases of gonadal and extragonadal primary were included in the nationwide cohort.
      The treatments were surveillance only; retroperitoneal radiotherapy (RT);
      bleomycin, etoposide, and cisplatin (BEP); or more than 1 line of treatment
      (MTOL). Main Outcomes and Measures: Cumulative incidence and hazard ratios (HRs)
      for SMN and death calculated by the Cox proportional hazards model were compared
      with those of age-matched controls. Results: The study population comprised 2804
      patients with seminoma and 2386 with nonseminoma. The median follow-up was 14.4
      years (interquartile range, 8.6-20.5 years). The 20-year cumulative incidence of
      SMN with death as a competing risk was 7.8% (surveillance), 7.6% (BEP), 13.5%
      (RT), 9.2% (MTOL), and 7.0% (controls). We found no increased risk for SMN after
      surveillance, while the HRs were 1.7 (95% CI, 1.4-2.0), 1.8 (95% CI, 1.5-2.3),
      and 3.7 (95% CI, 2.5-5.5), respectively, after BEP, RT, and MTOL. Mortality owing
      to non-GCC causes was decreased after surveillance, but increased by 1.3 times
      after BEP and RT and by 2.6 times after MTOL. Excess mortality due to SMN was
      found after BEP (HR, 1.6; 95% CI, 1.2-2.2), RT (HR, 2.1; 95% CI, 1.5-2.9), and
      MTOL (HR, 5.8; 95% CI, 3.6-9.6). Conclusions and Relevance: We found no increased
      risk for SMN or death among patients undergoing surveillance only. The risks for
      SMN and death due to SMN were increased after BEP alone, RT alone, and MTOL.
      Approaches to define patients who might benefit from less intensive treatment are
      needed.

PMID- 27711916
TI  - Intimacy, Body Image, and Cancer.

PMID- 27711915
TI  - Palatal Motion After Primary and Secondary Furlow Palatoplasty.
AB  - Importance: Indications for Furlow palatoplasty include primary repair of cleft
      palate as well as secondary repair, or secondary palatoplasty for treatment of
      velopharyngeal insufficiency. Speculation exists surrounding the benefit of
      secondary Furlow palatoplasty in cases of a previously well-reconstructed palate
      or a short but otherwise anatomically normal soft palate because it has been
      theorized that reorientation of a previously reconstructed or normal muscular
      levator sling should in fact worsen palatal motion. Objective: To compare palatal
      motion following primary and secondary Furlow palatoplasty using footage from
      postoperative nasopharyngoscopy videos. Design, Setting, and Participants: In
      this retrospective case series, medical records in a database of an urban
      academic pediatric otolaryngology practice was used to identify patients who had
      undergone either primary or secondary Furlow palatoplasty. Subjects with adequate
      postoperative nasopharyngoscopy footage were randomized, and 2 blinded reviewers
      assessed soft palate motion in each video using an abbreviated version of the
      Golding-Kushner scale. Main Outcomes and Measures: Reviewers' blinded ratings of
      soft palate motion were quantified using a modified Golding-Kushner scale to
      generate a mean palatal motion score for each subject (range, 0.0-2.0). Scores of
      primary and secondary Furlow palatoplasty patients were compared. Results: Over a
      4-year period, 20 patients with adequate postoperative nasopharyngoscopy footage
      were identified (12 primary Furlow palatoplasty patients and 8 secondary Furlow
      palatoplasty patients). Patients consisted of 8 males and 12 females and ranged
      in age from 12 months to 22 years at the time of postoperative nasopharyngoscopy.
      Modified Golding-Kushner scores were similar between groups: mean primary group,
      1.61 (range, 0.5-2.0); mean secondary group, 1.53 (range, 0.75-2.0); absolute
      difference in mean, 0.08 (95% CI, 0.00-0.43); effect size, Hedges g, 0.18. There
      was fair interrater reliability (interclass coefficient, R = 0.45), consistent
      with prior reports using this scale. No significant difference in postoperative
      palatal motion scores was identified between primary and secondary palatoplasty
      groups in this study. Conclusions and Relevance: When examined in isolation,
      postoperative motion of the soft palate appears similar following both primary
      and secondary Furlow palatoplasty procedures, suggesting that there are no major
      deleterious effects on palatal motion following secondary Furlow palatoplasty.

PMID- 27711917
TI  - Advances in 3-Dimensional Printing in Otolaryngology: A Review.
AB  - Importance: Three-dimensional (3-D) printing is an exponentially growing
      technology that enables the use of a patient's image data to create patient
      specific models, devices, and implants. Three-dimensional printing, developed in
      the 1980s, has emerged in the past decade with the potential to create new
      paradigms in personalized medicine. Observations: The field of otolaryngology has
      advanced many current and evolving future medical applications of 3-D printing.
      The predominant uses of 3-D printing have rapidly progressed from patient
      specific models and simulators to intraoperative guides. Continued advancements
      now include 3-D-printed implants and future tissue-engineered constructs, which
      bring new regulatory challenges. This review summarizes the literature and
      provides a comprehensive guide to the background, applications, and current
      limitations of 3-D printing across the head and neck. Conclusions and Relevance:
      Three-dimensional printing enables the rapid production of patient-specific
      devices for personalized medicine. The field of otolaryngology has pioneered many
      of the underlying advancements in medical 3-D printing and will continue to
      remain at the forefront of 3-D printing technology.

PMID- 27711918
TI  - Anti-Vascular Endothelial Growth Factor Comparative Effectiveness Trial for
      Diabetic Macular Edema: Additional Efficacy Post Hoc Analyses of a Randomized
      Clinical Trial.
AB  - Importance: Post hoc analyses from the Diabetic Retinopathy Clinical Research
      Network randomized clinical trial comparing aflibercept, bevacizumab, and
      ranibizumab for diabetic macular edema (DME) might influence interpretation of
      study results. Objective: To provide additional outcomes comparing 3 anti
      vascular endothelial growth factor (VEGF) agents for DME. Design, Setting, and
      Participants: Post hoc analyses performed from May 3, 2016, to June 21, 2016, of
      a randomized clinical trial performed from August 22, 2012, to September 23,
      2015, of 660 participants comparing 3 anti-VEGF treatments in eyes with center
      involved DME causing vision impairment. Exposures: Randomization to intravitreous
      aflibercept (2.0 mg), bevacizumab (1.25 mg), or ranibizumab (0.3 mg) administered
      up to monthly based on a structured retreatment regimen. Focal/grid laser
      treatment was added after 6 months for the treatment of persistent DME. Main
      Outcomes and Measures: Change in visual acuity (VA) area under the curve and
      change in central subfield thickness (CST) within subgroups based on whether an
      eye received laser treatment for DME during the study. Results: Post hoc analyses
      were performed for 660 participants (mean [SD] age, 61 [10] years; 47% female,
      65% white, 16% black or African American, 16% Hispanic, and 3% other). For eyes
      with an initial VA of 20/50 or worse, VA improvement was greater with aflibercept
      than the other agents at 1 year but superior only to bevacizumab at 2 years. Mean
      (SD) letter change in VA over 2 years (area under curve) was greater with
      aflibercept (+17.1 [9.7]) than with bevacizumab (+12.1 [9.4]; 95% CI, +1.6 to
      +7.3; P < .001) or ranibizumab (+13.6 [8.5]; 95% CI, +0.7 to +6.0; P = .009).
      When VA was 20/50 or worse at baseline, bevacizumab reduced CST less than the
      other agents at 1 year, but at 2 years the differences had diminished. In
      subgroups stratified by baseline VA, anti-VEGF agent, and whether focal/grid
      laser treatment was performed for DME, the only participants to have a
      substantial reduction in mean CST between 1 and 2 years were those with a
      baseline VA of 20/50 or worse receiving bevacizumab and laser treatment (mean
      [SD], -55 [108] um; 95% CI, -82 to -28 um; P < .001). Conclusions and Relevance:
      Although post hoc analyses should be viewed with caution given the potential for
      bias, in eyes with a VA of 20/50 or worse, aflibercept has the greatest
      improvement in VA over 2 years. Focal/grid laser treatment, ceiling and floor
      effects, or both may account for mean thickness reductions noted only in
      bevacizumab-treated eyes between 1 and 2 years. Trial Registration:
      clinicaltrials.gov Identifier NCT01627249.

PMID- 27711919
TI  - Decreased Vision and Cognitive Decline.

PMID- 27711920
TI  - Association of Adjuvant Tamoxifen and Aromatase Inhibitor Therapy With
      Contralateral Breast Cancer Risk Among US Women With Breast Cancer in a General
      Community Setting.
AB  - Importance: Within 10 years after breast cancer diagnosis, roughly 5% of patients
      develop contralateral breast cancer (CBC). Randomized trials have found that
      therapy including tamoxifen citrate and aromatase inhibitors (AIs) reduces CBC
      risk. But little is known about the magnitude and duration of protective
      associations within the context of real-world clinical management settings, where
      varying durations of and gaps in treatment are common. Objective: To determine
      the association between adjuvant tamoxifen and AI therapy and CBC risk within a
      general community setting. Design, Setting, and Participants: A retrospective
      cohort study of CBC risk among 7541 patients diagnosed with a first primary
      unilateral invasive breast cancer at Kaiser Permanente Institute for Health
      Research (Colorado) or Kaiser Permanente Northwest Center for Health Research
      (Oregon) between January 1, 1990, and December 31, 2008. Data were analyzed from
      1 year after diagnosis of the first breast cancer through the earliest of the
      following events: CBC diagnosis, other second cancer diagnosis, death, last tumor
      registry follow-up, exit from the Kaiser Permanente health care plan, or end of
      study follow-up (December 31, 2010, for Oregon and December 31, 2011, for
      Colorado). Exposures: Adjuvant tamoxifen use and AI therapy were treated as time
      dependent exposures, assessed using electronic prescription records. Main
      Outcomes and Measures: Incident CBC based on long-term systematic follow-up.
      Results: Among 7541 women with invasive breast cancer, median age at initial
      breast cancer diagnosis was 60.6 years (age range, 24.9-84.9 years). Women were
      predominantly (92.9% [7009 of 7541]) of white race. During a median of 6.3 years
      (range, 1-20.9 years) of follow-up, 248 women developed CBC (45 in situ and 203
      invasive). Contralateral breast cancer risk decreased significantly with
      increasing tamoxifen therapy duration. In current users, the relative risk (RR)
      per year of tamoxifen use was 0.76 (95% CI, 0.64-0.89), with an estimated 66%
      (RR, 0.34; 95% CI, 0.29-0.40) RR reduction for 4 years of use compared with
      nonusers. Risk reductions were slightly smaller for past users but were still
      significant at least 5 years after stopping tamoxifen therapy (RR per year of
      use, 0.85; 95% CI, 0.71-0.995). In addition, AI use without tamoxifen therapy was
      associated with reduced CBC risk (RR for AI users compared with nonusers, 0.48;
      95% CI, 0.22-0.97). Risk reductions were most apparent among women whose primary
      and CBCs were estrogen receptor positive. Conclusions and Relevance: Tamoxifen
      therapy was associated with reduced CBC risk during treatment and after its
      cessation, with risk progressively decreasing as tamoxifen therapy duration
      increased. Among those surviving at least 5 years, tamoxifen use for at least 4
      years was estimated to prevent 3 CBCs per 100 women by 10 years after an estrogen
      receptor-positive first breast cancer, an absolute risk reduction that is
      consistent with findings from clinical trials. If adjuvant endocrine therapy is
      indicated for breast cancer treatment, these findings in concert with trial data
      suggest that women should be encouraged to complete the full course.

PMID- 27711921
TI  - Drug Price Inflation and the Cost of Assisted Death for Terminally Ill Patients
      Death With Indignity.

PMID- 27711922
TI  - Sociodemographic Factors Associated With Knowledge and Risk Perception of Human
      Papillomavirus and Human Papillomavirus-Associated Oropharyngeal Squamous Cell
      Carcinoma Among a Predominantly Black Population.
AB  - Importance: The incidence of human papillomavirus (HPV)-associated oropharyngeal
      squamous cell carcinoma (OPSCC) is increasing in the United States and may be
      underestimated among black individuals. Characterizing the current knowledge
      level among black individuals is critical to developing interventions to increase
      awareness. Objective: To describe the sociodemographic correlates of knowledge
      and risk perception of HPV and HPV-associated OPSCC among a predominantly black
      population. Design, Setting, and Participants: A cross-sectional survey was
      conducted at a drag racing event on September 12 and 13, 2015, in Madison,
      Illinois. The setting was a community-based oral head and neck cancer screening
      and education initiative. Participants were 301 drag race attendees 18 years or
      older who were conveniently sampled from attendees at an annual drag racing event
      predominantly patronized by black individuals. Main Outcomes and Measures: The
      primary outcome was knowledge and risk perception of HPV and HPV-associated
      OPSCC. An electronic-based questionnaire elicited sociodemographic information
      and contained oral cancer knowledge and risk perception items, which were
      combined to form knowledge and risk perception scores. Multivariable linear
      regression analysis assessed estimates of knowledge and risk perception of HPV
      and HPV-associated OPSCC. Results: Of the 301 participants (111 female and 190
      male) completing the questionnaire, 194 (64.5%) were black. Overall, respondents
      ranged in age from 18 to 78 years, with a mean (SD) age of 48.0 (13.0) years. The
      mean (SD) knowledge score was 5.7 (4.6) of 15, and the mean (SD) risk perception
      score was 2.2 (1.4) of 6. Using multivariable linear regression, we found that,
      for every 1-year increase in age, knowledge of HPV-associated OPSCC decreased by
      5.0% and was worse in men (beta = -1.26; 95% CI, -2.33 to -0.18), black vs white
      individuals (beta = -1.29; 95% CI, -2.35 to -0.23), and those with a high school
      diploma or less vs college graduates (beta = -3.23; 95% CI, -4.67 to -1.80).
      Black individuals also had lower perceived risk of developing HPV-associated
      OPSCC (beta = -0.36; 95% CI, -0.69 to -0.02) compared with white individuals, and
      participants with a high school diploma or less had lower perceived risk of
      developing HPV-associated OPSCC compared with those with a college degree or
      higher (beta = -0.59; 95% CI, -1.04 to -0.14). Conclusions and Relevance: Age and
      sex were independent correlates of knowledge of HPV-associated OPSCC, while race
      and education level were correlates of both knowledge and risk perception of HPV
      associated OPSCC. These findings should inform future interventions targeted at
      increasing knowledge of HPV-associated OPSCC in black communities.

PMID- 27711923
TI  - Yield Strength Testing in Human Cadaver Nasal Septal Cartilage and L-Strut
      Constructs.
AB  - Importance: To our knowledge, yield strength testing in human nasal septal
      cartilage has not been reported to date. An understanding of the basic mechanics
      of the nasal septum may help surgeons decide how much of an L-strut to preserve
      and how much grafting is needed. Objectives: To determine the factors correlated
      with yield strength of the cartilaginous nasal septum and to explore the
      association between L-strut width and thickness in determining yield strength.
      Design, Setting, and Participants: In an anatomy laboratory, yield strength of
      rectangular pieces of fresh cadaver nasal septal cartilage was measured, and
      regression was performed to identify the factors correlated with yield strength.
      To measure yield strength in L-shaped models, 4 bonded paper L-struts models were
      constructed for every possible combination of the width and thickness, for a
      total of 240 models. Mathematical modeling using the resultant data with trend
      lines and surface fitting was performed to quantify the associations among L
      strut width, thickness, and yield strength. The study dates were November 1,
      2015, to April 1, 2016. Main Outcomes and Measures: The factors correlated with
      nasal cartilage yield strength and the associations among L-strut width,
      thickness, and yield strength in L-shaped models. Results: Among 95 cartilage
      pieces from 12 human cadavers (mean [SD] age, 67.7 [12.6] years) and 240
      constructed L-strut models, L-strut thickness was the only factor correlated with
      nasal septal cartilage yield strength (coefficient for thickness, 5.54; 95% CI,
      4.08-7.00; P < .001), with an adjusted R2 correlation coefficient of 0.37. The
      mean (SD) yield strength R2 varied with L-strut thickness exponentially (0.93
      [0.06]) for set widths, and it varied with L-strut width linearly (0.82 [0.11])
      or logarithmically (0.85 [0.17]) for set thicknesses. A 3-dimensional surface
      model of yield strength with L-strut width and thickness as variables was created
      using a 2-dimensional gaussian function (adjusted R2 = 0.94). Estimated yield
      strengths were generated from the model to allow determination of the desired
      yield strength with different permutations of L-strut width and thickness.
      Conclusions and Relevance: In this study of human cadaver nasal septal cartilage,
      L-strut thickness was significantly associated with yield strength. In a bonded
      paper L-strut model, L-strut thickness had a more important role in determining
      yield strength than L-strut width. Surgeons should consider the thickness of
      potential L-struts when determining the amount of cartilaginous septum to harvest
      and graft. Level of Evidence: NA.

PMID- 27711924
TI  - The Patient I Thought I Knew.

PMID- 27711925
TI  - Peripapillary Capillary Dilation in Leber Hereditary Optic Neuropathy Revealed by
      Optical Coherence Tomographic Angiography.

PMID- 27711927
TI  - The Rising Price of Cancer Drugs-A New Old Problem?

PMID- 27711928
TI  - Highlights of Recent Studies of Metastatic Non-Small Cell Lung Cancer.

PMID- 27711926
TI  - Photoreceptor Arrangement Changes Secondary to Choroidal Nevus.
AB  - Importance: Although mostly asymptomatic, patients with choroidal nevi carry a
      moderate risk for malignant transformation and visual loss. A novel noninvasive
      imaging assessment could change the current clinical evaluation of choroidal
      nevi. Observation: Three patients with a recent diagnosis of choroidal nevi
      underwent a novel adaptive optical assessment that detected potential
      photoreceptor abnormalities in the retina overlying the choroidal nevi.
      Conclusions and Relevance: Adaptive optics imaging may provide high-resolution en
      face images of retinal structural changes in the photoreceptor mosaic overlying
      the choroidal nevi. Cone attenuation may be an important component of structural
      damage in choroidal nevi and may correlate and possibly predict functional visual
      loss.

PMID- 27711929
TI  - Life Experiences of Caring for Pets Among Taiwanese Community-Dwelling Older
      Adults: Pets as an Integral Part of the Family and Beyond.
AB  - The purpose of the current study was to use grounded theory to explore the
      experiences of caring for pets from the perspective of Taiwanese community
      dwelling older adults. Twelve participants ages 65 to 73 were interviewed. Data
      were analyzed using the constant comparative method of qualitative analysis. Pets
      as an integral part of the family unit and beyond was the core category. The pet
      becomes part of my family was identified as the antecedent condition; this
      process undertakes action and interaction among the categories of the pet is part
      of my daily life, the pet provides positive life energy, and the pet is a sweet
      companion. Older adults believe caring for pets can bring them self-affirmation
      and lead them to blessings and luck. The results provide a framework to
      understand the experiences of older adults who reside with their pets, and serve
      as a guide for the design of animal-assisted therapy in future research and
      practice. [Journal of Gerontological Nursing, 43(1), 44-49.].

PMID- 27711930
TI  - Morbidity and Mortality Following Relocation of Highly Dependent Long-Term Care
      Residents: A Retrospective Analytical Study.
AB  - In recent years, 1,200 long-term care facility (LTCF) beds have been closed in
      Ireland, resulting in residents being transferred between facilities. The current
      study examined morbidity and mortality in residents relocated between LTCFs. The
      outcomes were studied for residents who transferred between LTCFs compared to
      residents who did not move (i.e., controls). A retrospective analysis was
      performed recording demographic data and markers of function and frailty. As a
      measure of morbidity, new antidepressant medication prescriptions and antibiotic
      drug use were examined. Mortality at 30 and 90 days was recorded. In total, 76
      transferred residents and 62 control residents were studied. Both groups were
      highly dependent and had a high 90-day mortality rate (18.4% versus 17.7%).
      Higher prescription rates of antibiotic drugs occurred among relocated residents
      prior to transfer (59.2% versus 27.4%, p = 0.017). Residents who transferred had
      a greater number of new antidepressant medication prescriptions than control
      residents (19.7% versus 8.1%, p = 0.05). Proper planning and vigilance by staff
      are essential to minimize any distress caused to residents during times of
      relocation. [Journal of Gerontological Nursing, 42(11), 34-38.].

PMID- 27711931
TI  - Managing Challenging Behaviors of Dementia in Veterans: Identifying and Changing
      Activators and Consequences Using STAR-VA.
AB  - One of the most challenging clinical issues for long-term care staff is the
      management of dementia-related behavioral symptoms. STAR-VA is an
      interdisciplinary intervention for managing challenging behaviors of Veterans
      with dementia in Community Living Centers (CLCs) within the U.S. Department of
      Veterans Affairs. The goals of the current article are to delineate categories of
      challenging behaviors found in CLCs, the context in which behaviors occurred, and
      the interventions used by CLC clinical teams when implementing STAR-VA. In 2013,
      17 CLC teams completed STAR-VA training, enrolling 71 Veteran participants. Four
      independent raters identified common assessment and intervention themes for six
      behavior categories, coding activators, consequences, goal behaviors, and care
      plans for each category. Successful care plans included staff changes in
      communication approaches, incorporation of pleasant events into care, and
      individualized environmental modifications. Findings illustrate the range of
      interventions that CLC teams may apply as a result of systematic behavioral
      assessment informing an understanding of activators and consequences of dementia
      related behaviors. [Journal of Gerontological Nursing, 43(2), 33-43.].

PMID- 27711932
TI  - Behavioral Symptoms of Dementia that Present Management Difficulties in Nursing
      Homes: Staff Perceptions and Their Concordance With Informant Scales.
AB  - The current study aimed to profile behaviors associated with dementia that pose
      management difficulties for staff and determine whether existing rating scales
      capture these reported behaviors. Staff in 17 nursing homes described the
      behavioral symptoms of 229 residents with predominantly moderate-severe dementia
      associated with management difficulties. Behaviors were categorized by an expert
      clinical panel and compared to items in four dementia behavior rating scales.
      Staff reported 59 discrete behavioral symptoms, with physically agitated,
      aggressive verbal, non-aggressive verbal, and aggressive physical behaviors most
      common, followed by resistance to care and inappropriate social and sexual
      behaviors. Results suggested that some scales omit important behaviors reported
      by staff for residents with particularly challenging behaviors. The current study
      highlights the clinical complexity faced by nursing home staff in managing
      residents with behavioral symptoms of dementia. [Journal of Gerontological
      Nursing, 43(1), 34-43.].

PMID- 27711934
TI  - Relevant areas of functioning in patients with adolescent idiopathic scoliosis on
      the International Classification of Functioning, Disability and Health: The
      patients' perspective.
AB  - OBJECTIVE: To investigate relevant aspects of functioning and disability, and
      environmental factors in people with adolescent idiopathic scoliosis according to
      patients' self-reports based on the International Classification of Functioning,
      Disability and Health for Children and Youth (ICF-CY). DESIGN: Multicentre,
      empirical, cross-sectional study. SETTING: Four departments of orthopaedics in 4
      hospitals, and 5 departments of rehabilitation medicine in 5 hospitals. METHODS:
      Semi-structured interviews were conducted with 975 patients with adolescent
      idiopathic scoliosis from 5 hospitals according to the patients' self-reporting.
      In addition, patients were divided into 3 groups according to clinical outcome.
      Participant information included demographic and disease-related characteristics.
      Three adolescent idiopathic scoliosis groups were then compared with respect to
      the problems identified. Interviews were transcribed verbatim. Categories
      identified by qualitative analysis were subsequently mapped to the ICF-CY using
      established linking rules. In order to enrich these findings, we also translated
      the Scoliosis Research Society 22 Patient Questionnaire (SRS-22 PQ) into the
      language of the ICF-CY, based on ICF linking rules. RESULTS: A total of 1278
      themes that linked to 54 ICF-CY cate-gories from 18 chapters were identified.
      Twenty-two (41%) categories were identified as Body Functions, 7 (13%) as Body
      Structures, 15 (27%) as Activities and Participation, and 10 (19%) as
      Environmental Factors. Of the 54 categories, 45 (83%) were second-level, 5 (9%)
      were third-level, and 4 (7%) were fourth-level. Differences between the SRS-22 PQ
      results and our findings were observed for several ICF-CY categories. CONCLUSION:
      Patients with AIS reported activity limitations and participation restrictions
      combined with impaired body structures and functions. Environmental factors may
      act as a barrier to, or facilitator of, patient functioning in daily life. The
      ICF-CY provides a valuable framework for representing the complexity and
      multifaceted impact of AIS, and for comparing and examining the content of the
      SRS-22 PQ for AIS in children and adolescents. These results will be used to
      develop ICF Core Sets for AIS in China.

PMID- 27711935
TI  - Admission-Based Prevalence of Schizophrenia, Schizoaffective Disorder and Bipolar
      I Disorder in a Catchment Area in Sinop, Turkey.
AB  - OBJECTIVE: To provide registry-based prevalence estimates of schizophrenia,
      schizoaffective, and bipolar I (BPI) disorders in a defined area of Sinop,
      Turkey. MATERIAL AND METHODS: All patients that presented to primary and
      secondary health services over three year time (2009-2011) with diagnosis of
      psychotic disorder (F06.1, F06.2, F10.5, F12.5, F19.5, F20-29, F30-31, F32.3,
      F33.3, F39 in ICD-10) covering a population of 73,503 aged 15-64 were included
      via case registry systems. All accessed case records were pooled. Case
      ascertainment and diagnostic assessment were achieved through structured clinical
      interview for DSM-IV, phone interview, or farming a best-estimated diagnosis via
      records on registers. RESULTS: Registries provided 1,410 probable cases. The
      successful clinical reappraisal rate was 66.8% (n: 955) while, the final
      diagnoses were determined via phone interview or best-estimate diagnosis in the
      rest of the cases. Seven hundred twenty seven individuals were diagnosed with DSM
      IV yielding a prevalence of 9.8 per 1,000 (95% confidence interval [CI]: 8.2
      11.5). Registry-based prevalence of schizophrenia, schizoaffective disorder, BPI
      disorder, and depression with psychotic features were 3.6 (95% CI: 3.0-4.2), 1.1
      (95% CI: 0.8-1.4), 2.7 (95% CI: 2.0-3.3), and 1.0 (95% CI: 0.6-1.3) per 1,000,
      respectively. CONCLUSION: Ten individuals per 1,000 adult persons admit for any
      disorder with psychotic symptoms. Registry-based prevalence estimates are lower
      than the lifetime prevalence estimates. However, analyses of administrative data
      appear to provide information needed for effectively plan and implement
      psychiatric services.

PMID- 27711936
TI  - Evaluation of Changes in Anxiety and Depression Symptoms, and Sexual Functions in
      Patients Receiving Antidepressants: 3 Months-Long Naturalistic Follow-Up Study.
AB  - OBJECTIVE: The aim of this study was to study the change in sexual functions
      within 3 months period following the initiation of antidepressant treatment in
      psychiatry outpatients, and its relationship with the change in anxiety and
      depression symptoms. MATERIAL AND METHOD: Eighty two patients, who consecutively
      applied to the psychiatry outpatient clinic and who were prescribed
      antidepressants, were included in the study. Hamilton Depression Rating Scale,
      Hamilton Anxiety Rating Scale, General Assessment of Functioning Scale and
      Arizona Sexual Experience Questionnaire (ASEC) were administered to the patients
      at the first interview, then repeated on a monthly basis during 3 months.
      RESULTS: Fifty seven of the patients (69.50 %) has been diagnosed with sexual
      dysfunctions prior to the antidepressant treatment. During the third month after
      the antidepressant treatment, 24 patients in this group (42.11%) showed no
      impairment in ASEC scores, whereas 33 patients' (57.89%) scores were still at
      impairment level. Eight patients out of 25 (32%) who weren't diagnosed with
      sexual dysfunctions prior to the treatment were later diagnosed with sexual
      dysfunctions. Sexual dysfunctions correlated with patients' level of functioning,
      separately from anxiety and depression symptoms. RESULTS: Our study results show
      that the sexual dysfunction rate is quite high in psychiatric patients
      population. However, sexual dysfunctions rate which can be related to
      antidepressant treatment is 36%. It would be appropriate for clinicians to
      determine benefit-loss balance by considering patients' mental syndromes together
      with sexual functions.

PMID- 27711937
TI  - IL-4, TGF-?, NF-?B and MPO levels in Patients with Treatment Resistant
      Schizophrenia.
AB  - OBJECTIVE: Schizophrenia is a chronic psychotic disorder in which genetics and
      environmental factors such as infection and the corresponding immune response
      play a role in the etiopathogenesis. The aim of this study was to compare some
      immune factors such as nuclear factor-?B (NF-?B) activation, myeloperoxidase
      (MPO), the anti-inflammatory cytokine interleukin-4 (IL-4), and regulatory
      cytokine transforming growth factor-? (TGF-?) in schizophrenia patients and an
      age- and gender-matched control group. METHOD: Plasma levels of IL-4, TGF-?, MPO,
      and NF-?B activation in 20 subjects with treatment-resistant schizophrenia and 20
      age- and gender-matched healthy controls were analyzed. Disease severity was
      evaluated using the Brief Psychiatric Rating Scale (BPRS). RESULTS: Plasma TGF-?
      levels were found to be significantly lower and NF-?B to be significantly higher
      in antipsychotic treatment-resistant schizophrenia patients than in controls in
      this study. No significant differences were found between the patient and control
      groups for serum IL-4 and MPO levels. CONCLUSION: The low TGF-? level in
      treatment-resistant schizophrenia patients in the symptom exacerbation period
      indicates that there is inadequate Th1/Th2 balance. Large-scale studies are
      required to investigate whether this is responsible for resistance in
      schizophrenia. The fact that the increase in NF-?B that we found in treatment
      resistant schizophrenia patients in this study has also been reported in the
      first attack in untreated schizophrenia patients in previous studies indicates
      that NF-?B plays a role in the disorder's physiopathology from the beginning.

PMID- 27711938
TI  - The Effect of Medical Education on Attitudes Towards Schizophrenia: A Five-Year
      follow-Up Study.
AB  - OBJECTIVE: It has been widely acknowledged that the community and health
      professionals hold negative attitudes toward patients with impaired mental
      health. This constitutes a major obstacle for those patients in coping with their
      disease, managing their care, and hence regulating their lives. Although studies
      carried out in Turkey document the presence of stigma, they provide limited
      information about the ways for solving this problem. Drawing on the litrature,
      the present study investigated the effect of medical education on stigmatization.
      METHOD: During 2008/2009 academic year, 106 freshmen who were majoring in the
      Medical School at Celal Bayar University volunteered to participate in the
      present study. Participants have not yet received any theoretical or practical
      training on psychiatry. At the beginning of the study, they were informed about
      the purpose of the study and accordingly requested to fill a consent form. The 32
      item schizophrenia subscale of the Attitude Questionnaire developed by
      Psychiatric Investigations and Education Center (PAREM) was administered to the
      participants. Along with the questionnaire, they were also requested demographic
      information. After 5 years, the participants who completed their psychiatry
      internship were reassessed with the same instrument. RESULTS: 106 volunteers
      participated in the present study. The majority of the participants were females
      (54.7%) with equal balance of income and expidentures (65.1%) having a mental
      disease percentage of 5.6%. Findings showed that students' attitudes towards
      schizophrenic patients changed significantly positive as they proceed from first
      year to the fifth year. Results demonstrated that as students move through the
      years they report more positive attitudes in the areas of etiology of
      schizophrenia (p<0.01), treatment options (p<0.01), approach to schizophrenic
      patients (p<0.01), and social interactions (p<0.01). CONCLUSION: We claim that
      the development of positive attitudes should be integrated in to the mental
      health curriculum not only in particular years but also throughout the whole
      years of education. Along this continuum, we believe that students would become
      more aware of the needs of the schizophrenic patients and gain an on going
      intuition toward the difficulties that the patients encounter. Viewed together,
      at the stage of acquiring medical/psychological skills students should be given
      the opportunity to have direct contact with patients in order to give adequate
      response to patients' needs and thus observe the improvement at the end of the
      treatment.

PMID- 27711939
TI  - The Ege Agraphia Test Battery for Identifying the Writing Disorders in Cases with
      Mild Cognitive Impairment and Alzheimer's Disease.
AB  - OBJECTIVE: The purpose of this study is to create an agraphia test battery
      specific to Turkish language, to obtain normative data for the performance and
      error types of this test and to demonstrate its success in detecting cognitive
      disorders in mild cognitive impairment (MCI) cases that can't be diagnosed by
      formal neuropsychological tests due to the fact that writing is a complex
      function. METHOD: For this purpose, 20 healthy control (HC) subjects, 20 MCI
      cases and 20 Alzheimer's disease (AD) patients with Clinical Dementia Rating
      (CDR) of 1 were evaluated with Ege Agraphia Test Battery. RESULTS: Significant
      differences between the performance points and the error types of HC subjects,
      MCI cases and AD patients were obtained. As the cognitive impairment of the
      subjects in the study got worse, the writing skills also became worse revealing
      lower test points. Besides, some statistically significant differences between
      the error types of MCI cases and AD patients were found. CONCLUSION: Ege Agraphia
      Test Battery is not only a practical test, but also is the first defined agraphia
      test specific for Turkish language. Writing disorders in cases with MCI support
      the view that MCI is a transition period for AD. Further studies are required to
      increase the test data and proper rearrangements of the test battery.

PMID- 27711940
TI  - Construct Validity of Auditory Verbal Learning Test.
AB  - OBJECTIVE: Auditory Verbal Learning Test (AVLT) is frequently used in
      neuropsychology literature to comprehensively assess the memory. The test
      measures verbal learning as immediate and delayed free recall, recognition, and
      retroactive and proactive interference. Adaptation of AVLT to the Turkish society
      has been completed, whereas research and development studies are still underway.
      The purpose of the present study is to investigate the construct validity of the
      test in order to contribute to the research and development process. METHOD: In
      line with this purpose, the research data were obtained from 78 healthy
      participants aged between 20 and 69. The exclusion criteria included neurological
      and/or psychiatric disorders as well as untreated auditory/visual disorders. AVLT
      was administered to participants individually by two trained psychologists.
      RESULTS: Principal component analysis that is used to investigate the components
      represented by the AVLT scores consisted of learning, free recall and
      recognition, in line with the construct of the test. Distractors were also added
      to these two components in structural equation model. Analyses were carried out
      on descriptive level to establish the relatioships between age, education, gender
      and AVLT scores. CONCLUSION: These findings, which are consistent with the
      literature indicating that memory is affected by the developmental process,
      suggest that learning/free recall, recognition, and distractor scores of the AVLT
      demonstrate a component pattern consistent with theoretical knowledge. This
      conclusion suggests that AVLT is a valid measurement test for the Turkish
      society.

PMID- 27711941
TI  - Understanding Treatment Response and Resistance in Obsessive Compulsive Disorder
      in the Context of Cognitive Neuropsychological Model.
AB  - Cognitive-behavioral therapies (CBT), antidepressants and neuromodulation
      techniques are current treatment options used in various stages of treatment
      procedure for obsessive-compulsive disorder (OCD). The factors that disparate
      treatment options from psychological approaches to invasive surgical techniques
      in a psychiatric disorder have in common have scarcely been described in the
      relevant literature. Cognitive neuropsychological model (CNM) as a novel approach
      offers a common framework in which psychological and neurobiological models of
      different psychopathologies are reconciled by means of impaired emotional
      processing. In this paper, an integrated approach of disrupted top-down and
      bottom-up emotional processing has been described to understand the efficacy of
      the different treatment modalities for OCD. In this model, the cognitive therapy
      is proposed to contribute to the gradual breakdown of schemata through the effect
      on top-down emotional processing instead of acting on information processing
      biases directly. Antidepressant drugs and behavioral therapy are proposed to
      alter the brain's emotion processing in a bottom-up process. Resistance to
      pharmacotherapy and CBT is a common problem in the patients with OCD, and a lot
      of factors have been described as negative predictors of these treatment options.
      The severity of symptoms, presence of specific symptoms, poorer insight, high
      level of dissociation and family accommodation are the factors associated with
      resistance to both pharmacotherapy and CBT. The underlying reasons establishing
      an association between the presence of these diverse factors and treatment
      resistance were discussed in the context of CNM.

PMID- 27711942
TI  - Reversible Valproic Acid-Induced Parkinsonism and Cognitive Impairment in an
      Elderly Patient With Bipolar Disorder I.
AB  - Valproic acid (VPA) is approved by the Food and Drug Administration (FDA) for the
      treatment of manic or mixed episodes associated with bipolar disorder. VPA is
      also used off-label to treat other conditions in psychiatry such as impulse
      control disorders, major depression, and posttraumatic stress disorder (PTSD).
      Although VPA is mostly well-tolerated, common adverse effects include
      gastrointestinal symptoms (nausea, vomiting, diarrhea), neurological symptoms
      (sedation, ataxia, tremor), weight gain, and alopecia. Less common adverse
      effects include VPA-induced parkinsonism and cognitive impairment. We describe a
      patient who developed parkinsonism and cognitive impairment eight years after
      starting divalproex sodium for bipolar disorder, type I. Over time, the patient's
      parkinsonian symptoms progressed, and the motor symptoms were partially
      responsive to carbidopa/levodopa. Her mild cognitive impairment was, for the most
      part, stable on donepezil. Rapid discontinuation of divalproex sodium resolved
      the parkinsonian symptoms as well as the cognitive impairment. A brief review of
      the literature regarding VPA-induced parkinsonism and cognitive impairment in
      adults is included. Given the reversible nature and potential severity of VPA
      induced parkinsonism, improved recognition in psychiatric populations is
      critical, particularly after extended VPA exposure. To the best of our knowledge
      there are no reports describing the onset of VPA-induced parkinsonism in
      psychiatric patients more than eight years after starting VPA.

PMID- 27711943
TI  - Investigating Connectivity of Orbitomedial Prefrontal Region in a Patient with
      Traumatic Brain Injury.
AB  - The majority of the research studying the prefrontal region has focused on gray
      matter injury. However, recent studies show that damage to white matter also
      contributes to the development of cognitive impairment after traumatic brain
      injury (TBI). Through the use of diffusion tensor imaging (DTI), it is now
      possible to assess the white matter fiber pathways between brain regions. With
      Diffusion Tensor Tractography (DTT), fibers of interest can be three
      dimensionally reconstructed and associated measurements can be performed. In this
      paper, we present the case of an individual that suffered from panic attacks,
      behavioral changes, auditory hallucinations and disturbing bodily sensations
      after traumatic brain injury. The patient was evaluated with a detailed clinical
      and neuropsychological assessment, magnetic resonance imaging (MRI) and DTI. MRI
      revealed cystic encephalomalasia with a diameter of 3.4 cm in the left
      orbitomedial frontal region. With DTT, major white matter tracts of the
      traumatized area were compared with symmetrical tracts in the contralateral side.
      Streamline count for the right inferior fronto-occipital fasciculus (iFOF) was 54
      while no streamlines could be found for the left iFOF. For the left uncinate
      fasciculus and the left cingulum, streamline counts were significantly lower
      compared with the right side (62% and 34% lower; respectively). White matter
      damage in TBI can cause dysfunction of different brain regions through disruption
      of connections with the traumatized area. In this case report, we emphasized that
      symptoms were not limited with dysfunction of the traumatized region and the
      regular functions of other brain regions were also affected via the disturbance
      of connection pathways.

PMID- 27711944
TI  - [Options for the optimized therapy of Helicobacter pylori infection].

PMID- 27711945
TI  - [Laboratory requirements to diagnose viral hepatitis under the development of
      guidelines].
AB  - Infections with hepatitis B-, C- and D- viruses have a significant health burden.
      In Germany, the seroprevalence of HBs-Ag is calculated with 0.6 % and of HCV
      antibodies with 0.3 %. However, most patients are not diagnosed. Sequelae are
      liver-cirrhosis and hepatocellular carcinoma. Several S3-guidelines for the
      diagnosis and treatment of viral hepatitis have been established. However,
      implementation of guidelines is not easy to evaluate. To estimate the changes of
      medical knowledge and diagnostic procedures about viral hepatitis, 7 parameters
      of liver-diagnostics were elected to analyze the requirements profile in the
      years 2005 - 2011 in 4 German federal states. GPT/ALT showed no important change
      except the influence of the laboratory-reformation. HBs-Ag and HCV-Ab show only a
      minor increase in adults. The molecular differentiation of HBV-DNA and HCV-RNA
      showed changes up to 200 % in some regions; however, this might not be explained
      by more screening but rather increased treatment monitoring or new region
      specific regulations. The most significant increase was observed for HDV
      antibodies, but the amount of testing is still at a low level. The development
      and update of guidelines, the World-Hepatitis-Awareness-Day, and other specific
      nationwide activities did not result in a major increase in the screening of
      viral hepatitis with the exception of HDV. The results and the new treatment
      options against hepatitis C should motivate to continue the education in the
      field of viral hepatitis in an intensified manor.

PMID- 27711946
TI  - [Biosimilars in inflammatory bowel disease].
AB  - After the expiry date of the patent protection for Infliximab in 2013, the
      biosimilar CT-P13 was approved for indications in Crohn's disease and ulcerative
      colitis in adults as well as in children. The approval has been based on two
      randomized clinical studies indicating equivalence for the biosimilar with regard
      to pharmacokinetics, efficacy, as well as side-effects. The clinical experience
      since, in addition to multiple non-randomized studies, indicate a comparable
      efficacy and immunogenicity of the Infliximab biosimilar CT-P13 in inflammatory
      bowel disease. Thus, the introduction of the biosimilar as primary therapy seems
      to be justified. Tight monitoring of the safety of biosimilars with regard to
      efficacy and side effects has to be ensured.

PMID- 27711947
TI  - [Opportunities and challenges of extrapolation for biosimilars].
AB  - Although biosimilars approved in the European Union have proved to be safe and
      efficacious, their licensing requirements continue to be disputed by medical
      professionals. In particular, extrapolation to indications of the originator
      without one's own clinical data of the biosimilar is controversial. Conceptually,
      the development of biosimilars is derived from that of generics. However, due to
      their complexity and inherent variability, considerably more data are necessary
      for biosimilars to demonstrate comparability with the originator (the reference
      product) than for the usually low-molecular generics. Biosimilars increase
      competition and help contain healthcare, and they improve access for patients to
      valuable treatments with biologicals. However, biosimilar development is a
      laborious and lengthy process and requires major biotechnological know-how. The
      basis is comprehensive, structural, and functional characterization of the
      biosimilar and reference product as well as their comparison with suitable and
      sensitive methods. The clinical development programme is reduced and tailored to
      address remaining uncertainties and to confirm comparable clinical performance.
      Extrapolation of data to other indications of the reference product is the
      greatest cost advantage of biosimilar development, but must always be
      scientifically justified and, if necessary, substantiated by further data. The
      scientific principles underlying the comparability exercise for a biosimilar are
      the same as those applied to a change in the manufacturing process of an already
      licensed biological. In both cases, different versions of a biological substance
      are compared and the clinical relevance of observed differences is assessed.
      Competent authorities do have decades of experience in evaluating changes in the
      manufacturing process, which they can now apply to biosimilars. For approval of a
      biosimilar and extrapolation of data, the totality of the evidence from the
      complete comparability exercise is considered, as has been the case for the first
      biosimilar infliximab.

PMID- 27711948
TI  - Highly Porous Metaphyseal Cones in Revision Total Knee Arthroplasty: A Case
      Series.
AB  - Highly porous metaphyseal cones are used for the management of large bone defects
      in revision total knee arthroplasty. These cones fill defects and allow bony
      ongrowth while providing several sizing and offset options. In this case series,
      we evaluated three patients who received these latest generation metaphyseal
      cones. Specifically, these cases will be explored in detail with respect to
      history, indications, operative technique, and short-term outcomes. Overall,
      these newer generation porous coated cones are excellent options for large
      contained bone loss in the absence of infection, and they have demonstrated good
      clinical and radiological outcomes at short-term follow-up.

PMID- 27711949
TI  - Advanced endoscopic imaging: European Society of Gastrointestinal Endoscopy
      (ESGE) Technology Review.
AB  - Background and aim: This technical review is an official statement of the
      European Society of Gastrointestinal Endoscopy (ESGE). It addresses the
      utilization of advanced endoscopic imaging in gastrointestinal (GI) endoscopy.
      Methods: This technical review is based on a systematic literature search to
      evaluate the evidence supporting the use of advanced endoscopic imaging
      throughout the GI tract. Technologies considered include narrowed-spectrum
      endoscopy (narrow band imaging [NBI]; flexible spectral imaging color enhancement
      [FICE]; i-Scan digital contrast [I-SCAN]), autofluorescence imaging (AFI), and
      confocal laser endomicroscopy (CLE). The Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) system was adopted to define the strength of
      recommendation and the quality of evidence. Main recommendations:1. We suggest
      advanced endoscopic imaging technologies improve mucosal visualization and
      enhance fine structural and microvascular detail. Expert endoscopic diagnosis may
      be improved by advanced imaging, but as yet in community-based practice no
      technology has been shown consistently to be diagnostically superior to current
      practice with high definition white light. (Low quality evidence.) 2. We
      recommend the use of validated classification systems to support the use of
      optical diagnosis with advanced endoscopic imaging in the upper and lower GI
      tracts (strong recommendation, moderate quality evidence). 3. We suggest that
      training improves performance in the use of advanced endoscopic imaging
      techniques and that it is a prerequisite for use in clinical practice. A learning
      curve exists and training alone does not guarantee sustained high performances in
      clinical practice. (Weak recommendation, low quality evidence.) Conclusion:
      Advanced endoscopic imaging can improve mucosal visualization and endoscopic
      diagnosis; however it requires training and the use of validated classification
      systems.

PMID- 27711950
TI  - [Periprosthetic Acetabulum Fractures].
AB  - In contrast to periprosthetic fractures of the femur, periprosthetic fractures of
      the acetabulum are rare complications - both primary fractures and fractures in
      revision surgery. This topic is largely under-reported in the literature; there
      are a few case reports and no long term results. Due to an increase in life
      expectancy, the level of patients' activity and the number of primary joint
      replacements, one has to expect a rise in periprosthetic complications in general
      and periprosthetic acetabular fractures in particular. This kind of fracture can
      be intra-, peri- or postoperative. Intraoperative fractures are especially
      associated with insertion of cementless press-fit acetabular components or
      revision surgery. Postoperative periprosthetic fractures of the acetabulum are
      usually related to osteolysis, for example, due to polyethylene wear. There are
      also traumatic fractures and fractures missed intraoperatively that lead to some
      kind of insufficiency fracture. Periprosthetic fractures of the acetabulum are
      treated conservatively if the implant is stable and the fracture is not
      dislocated. If surgery is needed, there are many possible different surgical
      techniques and challenging approaches. That is why periprosthetic fractures of
      the acetabulum should be treated by experts in pelvic surgery as well as revision
      arthroplasty and the features specific to the patient, fracture and prosthetic
      must always be considered.

PMID- 27711951
TI  - Novel Heterozygous Genetic Variants in Patients with 46,XY Gonadal Dysgenesis.
AB  - 46,XY gonadal dysgenesis (GD) constitutes a rare group of disorders characterized
      by the presence of dysfunctional testes in genotypic males. The molecular
      etiology is not known in about 2 thirds of instances. The aim of this study was
      to identify the genetic cause in patients with 46,XY gonadal dysgenesis. Based on
      clinical, cytogenetic, and biochemical screening, 10 patients with 46,XY GD were
      recruited. Direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes was
      carried out for molecular analysis. Among 10 patients, 5 were diagnosed with
      complete gonadal dysgenesis (CGD), 3 with partial gonadal dysgenesis (PGD), and 3
      with testicular agenesis. Molecular analysis revealed 12 heterozygous genetic
      changes, 4 of which were novel. One (c.416T>A) was observed in evolutionary
      conserved region of DMRT1 gene in a patient with CGD and was found to be probably
      damaging on in silico analysis. Other 3 were identified in NR5A1 gene (c.990+22
      C>A, c.1387+1403T>A and p.131P), but their association with gonadal dysgenesis is
      not evident from our study. These genetic changes were absent in parents and 50
      healthy control samples, which were also studied. With targeted sequencing
      approach, a molecular diagnosis was made in only one patient with 46,XY GD. The
      application of new genomic technologies is required for the precise evaluation of
      these rare genetic defects.

PMID- 27711952
TI  - Are Thyroid Hormone Values Obtained in Hospitalized Elderly Patients
      Reproducible? - A Cohort Study.
AB  - It is unclear whether TSH should be obtained in elderly hospitalized patients as
      several factors associated with hospitalization influence these levels, which may
      not truly represent the thyroid status of the individual. All patients>=65 years
      old hospitalized in a geriatric ward in the years 2012-2014 had TSH measured
      irrespective of the cause for hospitalization. All patients in whom TSH levels
      were performed in an ambulatory setting 2-12 months following hospitalization
      were identified and these TSH levels were correlated with levels recorded during
      hospitalization. Factors influencing TSH reproducibility were identified through
      review of patients' medical records. Of 562 patients hospitalized during the
      study period, 198 had repeat ambulatory TSH measurements during follow-up. The
      Katz Index of Independence was higher (9.43+/-2.98 vs. 8.43+/-3.67 p=0.002) and
      cerebrovascular disease was less prevalent (15.6 vs. 25.2% p=0.014) in those who
      had a repeat TSH measurement compared with those who did not, but other baseline
      characteristics and TSH levels on admission were similar. Ambulatory TSH values
      were significantly correlated with those obtained during hospitalization
      (correlation coefficient=0.677), irrespective of baseline systolic blood
      pressure, cause of hospitalization, or admission albumin levels. Mean TSH
      difference between in-hospital and ambulatory was 0.65+/-2.36 mIU/l and in more
      than 94% of cases TSH values differed by less than 2 mIU/l between the 2
      measurements. In hospitalized patients>=65 years old, TSH levels are highly
      concordant with ambulatory values. TSH obtained during hospitalization may be
      used for making treatment decisions and has clinical utility in this population.

PMID- 27711953
TI  - [Safety of Hyaluronic Acid in Postoperative Treatment after Penetrating
      Keratoplasty].
AB  - BACKGROUND: The objective of this clinical trial was to confirm the safety of
      phosphate-free high molecular weight hyaluronate (HYLO(r)-GEL) as lubricant for
      postoperative care after penetrating keratoplasty. PATIENTS AND METHODS: 51 eyes
      were followed up 6 weeks after penetrating keratoplasty under therapy with
      phosphate-free high molecular weight hyaluronate. Visual acuity, intraocular
      pressure, conjunctival hyperaemia, conjunctival chemosis, corneal fluorescein
      staining, corneal infiltrates, corneal endothelial-epithelial decompensation,
      Descemet's folds, Tyndall effect, cells in the anterior chamber and subjective
      assessment of lacrimation, foreign body sensation, pressure sensation, burning,
      mucus and itching were recorded on the first, third and fifth postoperative days
      and six weeks postoperatively. Tolerance was rated by the patient and the
      attending ophthalmologist. RESULTS: The following objective parameters improved
      significantly from day 1 to week 6 in patients treated with phosphate-free high
      molecular weight hyaluronate: visual acuity, conjunctival hyperaemia,
      conjunctival chemosis, corneal fluorescein-staining, corneal endothelial
      epithelial decompensation, Descemet's folds, the maximum diameter of corneal
      erosion, Tyndall effect and cells in the anterior chamber. In addition, there was
      significant improvement in the course of the following subjective complaints:
      lacrimation, foreign body sensation, pressure sensation and itching. In total 63
      % (32/47) of the study patients reported excellent local tolerance of phosphate
      free high molecular weight hyaluronate on day one postoperatively. This
      proportion rose to 86 % (37/43) 6 weeks postoperatively. The safety of phosphate
      free high molecular weight hyaluronate was rated by the ophthalmologists as
      "perfect" in 92 %, as "acceptable" in 6 % and as "unacceptable" in 2 % of eyes.
      CONCLUSION: Therapy with phosphate-free high molecular weight hyaluronate results
      in significant improvements in objective findings and subjective symptoms after
      penetrating keratoplasty. Tolerance was rated as "excellent" by the
      ophthalmologist in 92 % of patients in the early postoperative follow-up.

PMID- 27711954
TI  - [Imagery Rescripting and Psychophysical Relations Based on the ImRs-Therapy
      Concept Used for Test Anxiety: Review and First Experience].
AB  - Imagery Rescripting (ImRs) is an emotion-focused treatment technique, which was
      developed for persons suffering from traumatic experiences. ImRs includes
      imaginary exposure and rescripting alongside cognitive re-structuring. The
      principle of ImRs is based on the activation of emotions and the structuring of
      dysfunctional affective-cognitive schemata. ImRs is an effective treatment for
      PTSD and could be adapted to suit other psychological disorders. The current
      state of research focuses primarily on the wide range of uses. To date,
      physiological processes during the imagery rescripting have not been explored.
      Because of this, together with the cooperation of colleagues at Bar-Ilan
      University in Israel, we have conducted a pilot study to investigate
      psychophysiological patterns during ImRS sessions. Specifically, we examine the
      effectiveness of a targeted 6-session protocol developed for the treatment of
      test anxiety on a student sample, during which we monitor the sympathetic
      response of both clients and therapists. First feedback from the participants
      supports the power of imagery.

PMID- 27711955
TI  - [Validation of a German-language Version of the Body Checking Questionnaire (BCQ)
      in Adolescents with Anorexia and Bulimia Nervosa].
AB  - Body-related checking behavior, as a behavioral manifestation of a disturbed body
      image, fosters the development and maintenance of eating disorders. The Body
      Checking Questionnaire (BCQ) is the most commonly used questionnaire for
      measuring body-related checking behavior internationally. To date, validation
      studies are only available for adult populations. Therefore, the aim of this
      study was to statistically test the German-language version of the BCQ in
      adolescents. A total of N=129 female adolescents were examined, comprising n=57
      with Anorexia Nervosa, n=24 with Bulimia Nervosa, and n=48 healthy female
      adolescents. A confirmatory factor analysis supports the subdivision of the BCQ
      into a general factor and the subfactors "overall appearance", "specific body
      parts" and "idiosyncratic checking", which was also found in the original
      version. The internal consistencies are good (alpha>=0.81), and the BCQ is able
      to differentiate well between adolescents with and without eating disorders.
      Significant correlations between the BCQ and other body image questionnaires
      point to a good convergent validity. The German-language BCQ thus constitutes a
      valid and reliable instrument for measuring body-related checking behavior among
      adolescents in clinical research and practice.

PMID- 27711956
TI  - [Psycho-Oncologic Care by a Consultation-Liaison Service - Differences between
      Oncologic Patients with and without Psychiatric Comorbidity].
AB  - Background: Psycho-oncologic consultation and liaison services (CLS) are mainly
      psychosomatic oriented teams in acute care hospitals. Their interventions are
      electively, setting-related or universal like in accredited centers. Objectives:
      We investigated whether clinical and care-related differences between cancer
      patients with and without psychiatric comorbidity exist as well as between
      patients treated in oncologic centers and aside thereof. We also investigated
      possible differences according to psychiatric as well as to oncologic diagnoses.
      Method: A 4-year study (2012-15, for center-related comparisons: 2013-15) in a
      regional hospital (520 beds, 18 wards, 6 oncologic centers) based on data from a
      basic documentation covering selected clinical as well as care variables. Data
      was been collected on occasion of each consultation (N=3441 corresponding to 2257
      patients). Associations between clinical and care-related variables were
      identified by means of chi-square, ANOVA, Scheffe post hoc tests as well as by
      means of multivariate linear and logistic regression models. Results: The sample
      was on average 64 years old, about 68% women, and they showed a distress about
      4.63. Affective disorders were found for 4.4% and adjustment disorders for 7.8%
      of the sample. Bivariate tests show that patients with psychiatric comorbidity
      (19%) and patients aside the centers (24%) were highly significant (p<0.001)
      clinically more impaired and received more intensive care by CLS. Within the
      centers the psychiatric comorbidity amounted on average 9% (range:4-16%), that
      was lower than aside the centers (33,5%). Multivariate regression models largely
      confirm the differences found in bivariate tests; no gender differences were
      found, but a negative association between age and care density. Discussion: This
      study supports that psychooncologic CLS follow a good practice, because patients
      with a higher clinical burden related to psychiatric comorbidity receive more
      intensive care. Comorbidity quotas found were lower than in other similar German
      investigations. Conclusions: Oncologic patients with psychiatric comorbidity
      should be identified by CLS because they have a larger clinical burden and more
      distress. The fact that older patients receive less face to face interventions
      may have to be balanced with systemic interventions. Care needs - and not only
      received care - have to be assessed in further research.

PMID- 27711957
TI  - Evaluation of Ovarian Reserve with AMH Level in Patients with Well-Differentiated
      Thyroid Cancer Receiving Radioactive Iodine Ablation Treatment.
AB  - Introduction: Radioactive iodine (RAI) ablation treatment is used for patients
      diagnosed with well-differentiated thyroid cancer in order to reduce the risk of
      recurrence. RAI ablation treatment can adversely affect gonads in males and
      females. In this study, we aimed to determine ovary damage and infertility risk
      due to RAI, using serum anti-Mullerian hormone (AMH) level, in females who
      received RAI ablation treatment. Materials and Methods: 45 female patients who
      have not gone through the menopause and had received RAI ablation treatment for
      well-differentiated thyroid cancer in premenopausal period, and 40 healthy
      females as control groups were included in this study. The serum AMH, follicle
      stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), thyroid
      stimulating hormone (TSH) and creatinine levels of the patients included in the
      study were analyzed and compared to those of the control group with similar
      demographical characteristics. Results: No differences were found between the
      patient group and control group in terms of age, height, weight, body mass index,
      LH, E2 and creatinine. The difference in AMH, FSH and TSH between both groups
      were found to be significant. There was no statistically significant relation
      between the age and AMH levels. Similarly, no statistically significant relation
      between RAI exposure duration and AMH levels was determined. When the patients
      below and above the age of 35 were compared with regard to AMH (2.95+/-1.79 and
      2.75+/-1.94, respectively) and FSH (5.45+/-1.63 and 5.99+/-3.06, respectively),
      the difference between them was found to be statistically insignificant.
      Oligo/anovulation was detected in 7 patients (15.6% of the patient group) after
      RAI treatment, 8 (17.8%) patients became pregnant after RAI treatment, and none
      of the patients, who were actively trying to get pregnant, were unable to achieve
      it. Conclusion: According to these results, it may be concluded that low AMH
      levels due to RAI treatment can cause damage to the ovaries of patients;
      nevertheless, considering the AMH levels and the absence of infertility in the
      patients, the infertility risk was found to be low.

PMID- 27711958
TI  - Sexual Functioning and Depressive Symptoms in Women with Diabetes and Prediabetes
      Receiving Metformin Therapy: A Pilot Study.
AB  - Aim:Metformin is a drug of choice for the management of type 2 diabetes mellitus.
      Very little is known about its effect on human sexual function. Methods: The
      study included 3 age- and weight-matched groups of premenopausal women:
      individuals with type 2 diabetes, women with prediabetes and healthy controls.
      All women with diabetes and 50% of those with prediabetes were then treated with
      metformin and complied with lifestyle modification. The remaining individuals,
      not receiving pharmacotherapy, only complied with dietary recommendations. Apart
      from measuring plasma glucose and assessing insulin sensitivity, all enrolled
      women completed questionnaires evaluating sexual function (Female Sexual Function
      Index - FSFI) and the presence and severity of depressive symptoms (Beck
      Depression Inventory-Second Edition - BDI-II) initially and after 6 months.
      Results: Women with diabetes had a lower total FSFI score, as well as lower
      scores for all domains: sexual desire, sexual arousal, lubrication, orgasm,
      sexual satisfaction and dyspareunia, and these scores correlated with a degree of
      insulin resistance. Women with prediabetes had lower scores for sexual desire and
      sexual satisfaction. Moreover, women with diabetes and prediabetes were
      characterized by a higher total BDI-II score. Metformin treatment not only
      normalized sexual desire and sexual satisfaction in both studied groups, but also
      normalized or improved the remaining domains of FSFI in patients with diabetes,
      and these effects correlated with an improvement in insulin resistance.
      Conclusions: Metformin treatment provides a beneficial effect on female sexual
      function and the strength of this effect depends on the degree of insulin
      resistance.

PMID- 27711959
TI  - Novel Approaches for the Treatment of Familial Hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal disorder characterized by
      increased levels of total cholesterol and low density lipoprotein (LDL)
      cholesterol.The extent of underdiagnosis and undertreatment of individuals with
      FH is largely unknown.The LDL-lowering capacity of statins in combination with
      other lipid-lowering drugs is maximally around 50-60%. FH patients have a
      strongly elevated LDL-C and in most cases maximal current treatment is not
      sufficient to reach the desired LDL targets.Therefore, FH patients have a large
      residual cardiovascular risk despite the use of statins and there is a medical
      need for new additional drugs to further lower LDL-C in patients with FH to
      improve their prognosis.PCSK9 inhibitors have shown great efficacy in lowering
      lipids with very few side effects. No synergism between statins and PCSK9
      inhibition was observed in many trials, allowing clinicians to select a statin
      dose before considering the initiation of PCSK9-inhibitor therapy.In patients
      with FH, who are at risk for markedly accelerated atherosclerosis and premature
      cardiovascular death, also treatment with lomitapide or mipomersen has the
      potential to reduce the risk of atherosclerotic cardiovascular disease and
      premature mortality.These new drugs will be probably reserved for the most
      severely affected FH patients and could help clinicians to reduce their residual
      cardiovascular risk.

PMID- 27711960
TI  - Phycology for the ecologist.

PMID- 27711961
TI  - Consistency in a marine algal-grazer interaction over multiple scales.
AB  - Coralline algae are conspicuous members of many marine assemblages, especially
      those characterized by intense grazing pressure. We explored whether articulated
      species, especially Corallina vancouveriensis, depend on grazing invertebrates to
      both establish and flourish in an exposed rocky intertidal setting, and whether
      this plant-grazer relationship varied over more than three orders of magnitude
      (~100->300,000 MUm). Three experimental manipulations, supplemented by
      observations on recruitment, demonstrated that (i) C. vancouveriensis failed to
      recover rapidly from disturbed areas when grazers were experimentally excluded;
      (ii) recruitment occurred in the presence of grazers; (iii) increasing surface
      texture of molded surfaces enhanced coralline recruitment more when grazers were
      present; and (iv) settlement occurred predominately in microtopographical low
      areas of a molded surface, whereas a competitively superior fleshy red alga
      tended to recruit to high areas. These results confirm that coralline algal
      establishment and persistence are enhanced by grazers and reveal that this
      relationship is consistent over a range of biologically relevant scales.

PMID- 27711962
TI  - Effects of a diet containing dried grape pomace on blood metabolites and milk
      composition of dairy cows.
AB  - BACKGROUND: The effect of a diet containing 15% grape pomace (GP) on the general
      health status and milk quality of dairy cows was assessed by plasma biochemistry
      and total polyphenol (TP) content, milk polyphenols, milk composition and milk
      protein fractions. RESULTS: Among the polyphenols measured by liquid
      chromatography-mass spectroscopy in GP, in feed containing GP (GP+) or not
      containing GP (GP-), gallic acid and epicatechin were present in the highest
      concentrations (67.58 and 19.23 ug mL-1 , respectively). Higher amounts of TP
      were also detected in the blood plasma of GP+ cows (114.06 and 83.93 mg GAE L-1 ,
      respectively) but not in their milk (233.17 and 245.75 mg GAE L-1 ,
      respectively). Also a significant increase was found for lactose and beta
      lactoglobulin, although there was no effect on alpha-lactalbumin, albumin,
      secretory components and caseins. CONCLUSION: Inclusion of 15% GP in the diets of
      dairy cows is beneficial for overall normal blood constituent metabolism and
      helps to maintain cow health. The milk of cows fed with a GP diet preserves the
      normal levels of fat, protein and caseins, and has increased levels of components
      that make this milk a versatile ingredient material for the food industry (e.g.
      model whey powders, stability of lactose-rich powders). (c) 2016 Society of
      Chemical Industry.

PMID- 27711963
TI  - Operative Techniques and Preliminary Outcomes Following Percutaneous Endoscopic
      Thoracolumbar Pediculectomy in Dogs.
AB  - OBJECTIVE: To examine the technical feasibility of percutaneous endoscopic
      pediculectomy using a lateral approach and to evaluate its use for decompression
      and examination of the thoracic and lumbar spinal canals in small dogs. STUDY
      DESIGN: Experimental study. ANIMALS: Clinically normal adult dogs (n=10).
      METHODS: After optimizing the technique in cadavers, percutaneous endoscopic
      pediculectomy was performed using a lateral approach to the thoracic (T12) or
      lumbar (L2) vertebrae in 5 dogs each. Using fluoroscopic guidance, a K-wire,
      dilator, and (cannula) working sleeve were placed. A window for visualizing the
      spinal cord and floor of the spinal canal was created using a specialized drill,
      rongeurs, trephine, and elevator. Gait and neurologic status were monitored
      postoperatively, and computed tomography (CT) and magnetic resonance imaging
      (MRI) performed. RESULTS: All procedures were completed successfully (T12, 45 +/-
      13 minutes; L2, 59 +/- 14 minutes) with clear observation of the spinal cord and
      floor of the spinal canal. Normal ambulation was maintained in 9 dogs. One dog in
      the L2 group had ipsilateral hind limb weakness that resolved within 4 days. One
      dog in the L2 group suffered a fracture of the accessory process. One dog each in
      the T12 and L2 groups had hyperintense lesions on T2-weighted MRI images,
      suspicious of focal edema, which reduced at 4 weeks after initial examination,
      possibly reflecting gliosis. CONCLUSION: Pediculectomy using a percutaneous
      endoscopic thoracolumbar lateral approach is feasible, provides a good view of
      the spinal canal, and may be an alternative for treatment of disk disease in
      dogs.

PMID- 27711965
TI  - Measuring circulating placental RNAs to non-invasively assess the placental
      transcriptome and to predict pregnancy complications.
AB  - Circulating nucleic acids have revolutionized prenatal diagnosis in the last
      decade, allowing non-invasive screening for single gene or chromosomal defects
      using a single sample of maternal blood. In addition to DNAs, RNAs from the
      placenta are released into the maternal blood from early in pregnancy and may
      reflect changes in gene expression occurring within the placenta. Measuring
      circulating RNA may therefore provide insights into the placental transcriptome
      without the need for invasive testing. Combined with advances in next-generation
      sequencing and molecular analyses, it may be possible to measure circulating RNA
      to improve our understanding of placental pathology and develop novel non
      invasive biomarkers for pregnancy complications and monitoring high-risk
      pregnancies. This review summarizes the current technologies available and the
      studies that have measured circulating placental RNA to predict and/or monitor
      pregnancies complicated by preeclampsia, fetal growth restriction, preterm birth,
      early pregnancy complications, invasive placentation and twin-twin transfusion
      syndrome. Prospective cohort studies are now required to validate these findings
      to determine the clinical applicability of measuring circulating placental RNA to
      develop novel biomarkers for a wide spectrum of pregnancy complications. (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27711964
TI  - Effects of combined treatment with ibandronate and pulsed electromagnetic field
      on ovariectomy-induced osteoporosis in rats.
AB  - Ibandronate (IBN) and pulsed electromagnetic field (PEMF) have each shown
      positive effects for treating osteoporosis, but no study has evaluated the
      relative effects of these treatments combined. This study investigated the
      effects of IBN + PEMF on bone turnover, mineral density, microarchitecture, and
      biomechanical properties in an ovariectomized (OVX) rat model of osteoporosis.
      Fifty 3-month-old rats were randomly apportioned to receive a sham-operation (n =
      10), or ovariectomy (n = 40). The latter group was equally divided as the model
      (OVX control) or to receive IBN, PEMF, or IBN + PEMF. Beginning the day after
      surgery, the IBN and IBN + PEMF groups received weekly subcutaneous IBN; the PEMF
      and IBN + PEMF groups were given daily PEMF during the same 12 weeks. After 12
      weeks of treatments, biochemical parameters, bone mineral density (BMD),
      microarchitecture parameters, biomechanical properties, and some metabolic
      modulators that are involved in bone resorption were compared. The L5 lumbar
      vertebral body BMDs of the IBN, PEMF, and IBN + PEMF groups were 121.6%, 119.5%,
      and 139.6%; maximum loads were 111.4%, 112.7%, and 121.9%; and energy to failure
      was 130.8%, 129.2%, and 154.9% of the OVX model, respectively. The IBN + PEMF
      group had significantly lower levels of serum tartrate-resistant acid phosphatase
      5b, and greater improvement in BMD, bone microarchitecture, and strength of the
      lumbar spine compared with monotherapy groups. Results showed that IBN + PEMF had
      a more favorable effect on the lumbar spine in this osteoporosis model than did
      either monotherapy. Bioelectromagnetics. 38:31-40, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27711966
TI  - An Argument for Fewer Clinical Trials.
AB  - The volume of clinical research is increasing exponentially-far beyond our
      ability to process and absorb the results. Given this situation, it may be
      beneficial to consider reducing the flow at its source. In what follows, I will
      motivate and critically evaluate the following proposal: researchers should
      conduct fewer clinical trials. More specifically, I c onsider whether researchers
      should be permitted to conduct only clinical research of very high quality and,
      in turn, whether research ethics committees (RECs) should prohibit all other,
      lower-quality research, even when it might appear to meet some minimal ethical
      standard. Following a close analysis of the social-value requirement of ethical
      clinical research, I argue that this proposal is defensible. The problem
      identified in this paper has two parts, quantity and quality, and some
      clarification is needed about the latter because "quality" is a highly contested
      term in the medical literature. When some scholars advocate for high-quality
      trials, they mean large-scale, simple, explanatory randomized controlled trials.
      Others, including myself, have defended a different characterization of high
      quality research that tends more toward pragmatic trial design and the use of
      methods other than RCTs. Pragmatic trials aim to provide evidence that directly
      supports clinical decision-making in "usual" care settings. Unlike explanatory
      trials, which aim to abstract away from particular settings and patients, in the
      hopes of creating ideal conditions for the success of an intervention, pragmatic
      trials deliberately pursue knowledge of high applicability, through the use of
      representative subjects, clinically important questions, flexible treatment
      protocols, patient-oriented outcome measures, and so on. I see applicability as a
      marker of high-quality research. The context in which research is meant to be
      applied should be the context in which new interventions are evaluated.

PMID- 27711967
TI  - Augmented Repair of an Achilles Tendon Rupture Using the Flexor Digitorum
      Lateralis Tendon in a Toy Poodle.
AB  - OBJECTIVE: To report appositional augmentation of Achilles tendon rupture in a
      toy breed dog with an intact flexor digitorum lateralis (FDL) muscle tendon.
      STUDY DESIGN: Clinical case report. ANIMALS: Two-year-old spayed female Toy
      Poodle with Achilles tendon rupture. METHODS: The Achilles tendon was
      accidentally ruptured by hair clippers during grooming. The dog demonstrated a
      plantigrade stance without digital flexion of the right hind limb. The ruptured
      gastrocnemius and superficial digital flexor tendons were sutured to their
      respective cut ends using a simple locking loop pattern under a surgical
      microscope. The repair site was appositionally augmented by the caudally
      retracted intact FDL. An aluminum splint was applied on the plantar aspect to
      immobilize the tarsal joint for the first 2 weeks, after which a soft bandage was
      applied for another 2 weeks. RESULTS: At the 7 month follow-up no lameness was
      detected during walking and no complications associated with decreased FDL
      function such as digital contracture were observed. The range of motion of the
      tarsal joint had improved and could be flexed to ~60 degrees  and extended fully.
      CONCLUSION: Use of the FDL is feasible for augmenting Achilles tendon repair in
      toy breed dogs.

PMID- 27711968
TI  - Efficacy of the MEK inhibitor cobimetinib for wild-type BRAF Erdheim-Chester
      disease.

PMID- 27711969
TI  - Survey of Molds in California Processing Tomatoes.
AB  - From 2009 to 2011, freshly harvested processing tomatoes from California
      commercial fields were surveyed for mold species present in the mature fruit.
      Molds were recovered from the majority of fruit that had visual symptoms of black
      mold and other decays and from about a quarter of randomly sampled, asymptomatic
      fruit. Alternaria, Fusarium, and Geotrichum spp. were the most commonly recovered
      fungi in both symptomatic and random samples. Based on pairwise statistical
      analysis, the frequencies of 2 different fungal genera in a composite 11 kg
      sample were, in general, statistically independent events, with the exception of
      a weak association between the incidence of Geotrichum with Alternaria,
      Cladosporium, or Stemphylium. The mold genera distribution data in this study
      provide the processing tomato industry with a valuable informational resource
      that can be used in the management of fungal infection in both the crop and in
      the final thermally processed finished product. Because of the relative abundance
      of these fungi, this survey supported the development of genera-specific
      immunochromatographic diagnostic assays to detect and quantify mold occurrence in
      Californian processing tomatoes as a potential alternative to the current
      subjective visual methods, which are characterized by imprecision and nonuniform
      species sensitivity. A simulation of 1 million 11 kg-composite samples based upon
      the distributional survey data projected that a multiantibody
      immunochromatographic assay using monoclonal antibodies for Alternaria,
      Cladosporium, Fusarium, and Geotrichum could successfully detect the presence of
      mold in 94% of moldy processing tomato samples collected randomly at harvest.

PMID- 27711970
TI  - Examining Consistency Between Self-Assessed and Peer-Rated Quality of Life in
      Older Persons.

PMID- 27711971
TI  - Future warming and acidification effects on anti-fouling and anti-herbivory
      traits of the brown alga Fucus vesiculosus (Phaeophyceae).
AB  - Human-induced ocean warming and acidification have received increasing attention
      over the past decade and are considered to have substantial consequences for a
      broad range of marine species and their interactions. Understanding how these
      interactions shift in response to climate change is particularly important with
      regard to foundation species, such as the brown alga Fucus vesiculosus. This
      macroalga represents the dominant habitat former on coastal rocky substrata of
      the Baltic Sea, fulfilling functions essential for the entire benthic community.
      Its ability to withstand extensive fouling and herbivory regulates the associated
      community and ecosystem dynamics. This study tested the interactive effects of
      future warming, acidification, and seasonality on the interactions of a marine
      macroalga with potential foulers and consumers. F. vesiculosus rockweeds were
      exposed to different combinations of conditions predicted regionally for the year
      2100 (+?5 degrees C, +?700 MUatm CO2 ) using multifactorial long-term experiments
      in novel outdoor benthic mesocosms ("Benthocosms") over 9-12-week periods in four
      seasons. Possible shifts in the macroalgal susceptibility to fouling and
      consumption were tested using consecutive bioassays. Algal susceptibility to
      fouling and grazing varied substantially among seasons and between treatments. In
      all seasons, warming predominantly affected anti-fouling and anti-herbivory
      interactions while acidification had a subtle nonsignificant influence.
      Interestingly, anti-microfouling activity was highest during winter under
      warming, while anti-macrofouling and anti-herbivory activities were highest in
      the summer under warming. These contrasting findings indicate that seasonal
      changes in anti-fouling and anti-herbivory traits may interact with ocean warming
      in altering F. vesiculosus community composition in the future.

PMID- 27711972
TI  - Distinct and shared three-dimensional chromosome organization patterns in
      lymphocytes, monoclonal gammopathy of undetermined significance and multiple
      myeloma.
AB  - The consistent appearance of specific chromosomal translocations in multiple
      myeloma has suggested that the positioning of chromosomes in the interphase
      nucleus might play a role in the occurrence of particular chromosomal
      rearrangements associated with malignant transformation. Using fluorescence in
      situ hybridization, we have determined the positions of selected chromosome pairs
      (18 and 19, 9 and 22, 4 and 14, 14 and 16, 11 and 14) in interphase nuclei of
      myeloma cells compared to normal lymphocytes of treatment-naive patients. All
      chromosome pairs were arranged in a nonrandom pattern. Chromosomes commonly
      involved in myeloma-associated translocations (4 and 14, 14 and 16, 11 and 14)
      were found in close spatial proximity, and this is correlated with the occurrence
      of overlapping chromosome territories. The spatial distribution of chromosomes
      may increase the possibility of chromosomal translocations in multiple myeloma.

PMID- 27711973
TI  - Pharmacological interventions other than botulinum toxin for spasticity after
      stroke.
AB  - BACKGROUND: The long-term risk of stroke increases with age, and stroke is a
      common cause of disability in the community. Spasticity is considered a
      significantly disabling impairment that develops in people who have had a stroke.
      The burden of care is higher in stroke survivors who have spasticity when
      compared with stroke survivors without spasticity with regard to treatment costs,
      quality of life, and caregiver burden. OBJECTIVES: To assess if pharmacological
      interventions for spasticity are more effective than no intervention, normal
      practice, or control at improving function following stroke. SEARCH METHODS: We
      searched the Cochrane Stroke Group Trials Register (May 2016), the Cochrane
      Central Register of Controlled Trials (CENTRAL, 2016, Issue 5), MEDLINE (1946 to
      May 2016), Embase (2008 to May 2016), CINAHL (1982 to May 2016), AMED (1985 to
      May 2016), and eight further databases and trial registers. In an effort to
      identify further studies, we undertook handsearches of reference lists and
      contacted study authors and commercial companies. SELECTION CRITERIA: We included
      randomised controlled trials (RCTs) that compared any systemically acting or
      locally acting drug versus placebo, control, or comparative drug with the aim of
      treating spasticity. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the studies for inclusion and extracted the data. We
      assessed the included studies for both quality and risk of bias. We contacted
      study authors to request further information when necessary. MAIN RESULTS: We
      included seven RCTs with a total 403 participants. We found a high risk of bias
      in all but one RCT. Two of the seven RCTs assessed a systemic drug versus
      placebo. We pooled data on an indirect measure of spasticity (160 participants)
      from these two studies but found no significant effect (odds ratio (OR) 1.66, 95%
      confidence interval (CI) 0.21 to 13.07; I2 = 85%). We identified a significant
      risk of adverse events per participant occurring in the treatment group versus
      placebo group (risk ratio (RR) 1.65, 95% CI 1.12 to 2.42; 160 participants; I2 =
      0%). Only one of these studies used a functional outcome measure, and we found no
      significant difference between groups.Of the other five studies, two assessed a
      systemic drug versus another systemic drug, one assessed a systemic drug versus
      local drug, and the final two assessed a local drug versus another local drug.
      AUTHORS' CONCLUSIONS: The lack of high-quality RCTs limited our ability to make
      specific conclusions. Evidence is insufficient to determine if systemic
      antispasmodics are effective at improving function following stroke.

PMID- 27711974
TI  - Next-generation sequencing-based detection of circulating tumour DNA After
      allogeneic stem cell transplantation for lymphoma.
AB  - Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection
      is a promising monitoring tool for lymphoid malignancies. We evaluated whether
      the presence of ctDNA was associated with outcome after allogeneic haematopoietic
      stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients
      drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in
      lymphoma. Conventional restaging and collection of peripheral blood samples
      occurred at pre-specified time points before and after HSCT and were assayed for
      ctDNA by sequencing of the immunoglobulin or T-cell receptor genes. Tumour
      clonotypes were identified in 87% of patients with adequate tumour samples.
      Sixteen of 19 (84%) patients with disease progression after HSCT had detectable
      ctDNA prior to progression at a median of 3.7 months prior to
      relapse/progression. Patients with detectable ctDNA 3 months after HSCT had
      inferior progression-free survival (PFS) (2-year PFS 58% vs. 84% in ctDNA
      negative patients, P = 0.033). In multivariate models, detectable ctDNA was
      associated with increased risk of progression/death (Hazard ratio 3.9, P = 0.003)
      and increased risk of relapse/progression (Hazard ratio 10.8, P = 0.0006).
      Detectable ctDNA is associated with an increased risk of relapse/progression, but
      further validation studies are necessary to confirm these findings and determine
      the clinical utility of NGS-based minimal residual disease monitoring in lymphoma
      patients after HSCT.

PMID- 27711975
TI  - Observational research rigour alone does not justify causal inference.
AB  - BACKGROUND: Differing opinions exist on whether associations obtained in
      observational studies can be reliable indicators of a causal effect if the
      observational study is sufficiently well controlled and executed. MATERIALS AND
      METHODS: To test this, we conducted two animal observational studies that were
      rigorously controlled and executed beyond what is achieved in studies of humans.
      In study 1, we randomized 332 genetically identical C57BL/6J mice into three diet
      groups with differing food energy allotments and recorded individual self
      selected daily energy intake and lifespan. In study 2, 60 male mice (CD1) were
      paired and divided into two groups for a 2-week feeding regimen. We evaluated the
      association between weight gain and food consumption. Within each pair, one
      animal was randomly assigned to an S group in which the animals had free access
      to food. The second paired animal (R group) was provided exactly the same diet
      that their S partner ate the day before. RESULTS: In study 1, across all three
      groups, we found a significant negative effect of energy intake on lifespan.
      However, we found a positive association between food intake and lifespan among
      the ad libitum feeding group: 29.99 (95% CI: 8.2-51.7) days per daily kcal. In
      study 2, we found a significant (P = 0.003) group (randomized vs. self-selected)
      by-food consumption interaction effect on weight gain. CONCLUSION: At least in
      nutrition research, associations derived from observational studies may not be
      reliable indicators of causal effects, even with the most rigorous study designs
      achievable.

PMID- 27711977
TI  - Evaluation of the Penetration of Multiple Classes of Pesticides in Fresh Produce
      Using Surface-Enhanced Raman Scattering Mapping.
AB  - Understanding pesticide penetration is important for effectively applying
      pesticides and in reducing pesticide exposures from food. This study aims to
      evaluate multiclass systemic and nonsystemic pesticide penetration in 3
      representative fresh produce (apples, grapes, and spinach leaves). Surface
      enhanced Raman scattering mapping was applied for in situ and real-time tracking
      of pesticide penetration over time. The results show that 100 mg/L of systemic
      pesticides, thiabendazole and acetamiprid, penetrated more rapidly and deeply
      with maximum depth around 220 MUm after 48-h exposure into the tested fresh
      produce than 100 mg/L of nonsystemic pesticides, ferbam and phosmet, with maximum
      depth about 80 MUm. The fact that 2 nonsystemic pesticides were also able to
      penetrate over time into all 3 fresh produce tested may raise additional food
      safety concerns. Comparatively, grapes were generally more resistant for
      pesticide penetration with all pesticides penetration depth below 80 MUm compared
      to apples and spinach leaves. The information obtained here could provide
      technical support and guidance for accurate, effective, and safe application of
      pesticides and for the reduction of pesticide exposure from fresh produce.

PMID- 27711976
TI  - Identification of peptide sequences that selectively bind to pentaerythritol
      trinitrate hemisuccinate-a surrogate of PETN, via phage display technology.
AB  - The present research investigates the identification of amino acid sequences that
      selectively bind to a pentaerythritol tetranitrate (PETN) explosive surrogate.
      Through the use of a phage display technique and enzyme-linked immunosorbent
      assays (ELISA), a peptide library was tested against pentaerythritol trinitrate
      hemisuccinate (PETNH), a surrogate of PETN, to screen for those with amino acids
      having affinity toward the explosive. The results suggest that the library
      contains peptides selective to PETNH. Following three rounds of panning, clones
      were picked and tested for specificity toward PETNH. ELISA results from these
      samples show that each phage clone has some level of selectivity for binding to
      PETNH. The peptides from these clones have been sequenced and shown to contain
      certain common amino acid segments among them. This work represents a
      technological platform for identifying amino-acid sequences selective toward any
      bio-chem analyte of interest.

PMID- 27711978
TI  - Development and validation of an assessment tool for a national young worker
      curriculum.
AB  - BACKGROUND: An online, multiple-choice assessment was developed and validated for
      Youth@Work-Talking Safety, a NIOSH curriculum that equips middle and high school
      students with foundational workplace safety and health knowledge and skills.
      METHODS: Classical Test Theory was used for the test development and validation;
      the Jaeger method was used for cut score determination. A total of 118 multiple
      choice items were developed to measure the acquisition of knowledge and skills
      taught through the NIOSH curriculum. Pilot testing was conducted with 192 8-12th
      grade students and a cut score was determined. RESULTS: The mean score for all
      test-takers on the Talking Safety assessment was 80.9%; total test reliability
      measured using an Alpha/KR20 statistic was 0.93. A minimum passing (cut) score of
      74% was established. CONCLUSIONS: The assessment provides an objective measure of
      students' acquisition of the foundational workplace safety and health
      competencies taught through the Talking Safety curriculum. Am. J. Ind. Med.
      59:969-978, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27711980
TI  - Interventions for patients and caregivers to improve knowledge of sickle cell
      disease and recognition of its related complications.
AB  - BACKGROUND: Sickle cell disease is a group of genetic diseases which is
      especially prevalent in tropical and subtropical regions; however, forced
      migration and ongoing population movement have spread it throughout the world,
      with estimated birth rates reaching 0.49 per 1000 in the Americas, 0.07 per 1000
      in Europe, 0.68 per 1000 in South and Southeast Asia, and 10.68 per 1000 in
      Africa. Life for individuals with sickle cell disease can be affected by repeated
      acute complications and compounded by progressive organ damage. Studies reveal
      that when people with chronic illness learn self-management, their clinical
      outcomes and quality of life improves; and they show lower dependence on
      healthcare services. There are, however, no reviews identifying which
      interventions improve knowledge and little is known about the impact of patient
      or care-giver knowledge on clinical and psychosocial outcomes in people with
      sickle cell disease. OBJECTIVES: 1. To determine the effectiveness of patient-
      and caregiver-centred educational interventions for changing knowledge and
      understanding of sickle cell disease among patients as well as caregivers of
      people with the disease.2. To assess the effectiveness and safety of patient- and
      caregiver-centred educational interventions and programs for the recognition of
      signs and symptoms of disease-related morbidity, adherence to treatment and
      healthcare utilization in patients with sickle cell disease. SEARCH METHODS: The
      authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
      Haemoglobinopathies Trials Register, compiled from electronic database searches
      and handsearching of journals and conference abstract books. Additional trials
      were sought from the reference lists of the trials and reviews identified by the
      search strategy.Date of last search: 11 April 2016. SELECTION CRITERIA:
      Randomized and quasi-randomized controlled trials which evaluate the
      effectiveness of individual- and group-based interventions for either the patient
      with sickle cell disease or their caregivers, or both. Eligible interventions
      will aim to change knowledge, attitudes or skills, improve psychosocial aspects
      of the disease as well as treatment adherence and healthcare utilization. Trials
      evaluating the intervention versus no program, comparing two interventions and
      those which are part of a multi-faceted intervention to improve a range of sickle
      cell-related health outcomes are all eligible for inclusion. DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected trials based on stated
      inclusion criteria and thereafter examined each selected report to extract data
      using a prepared, piloted, data collection form. A third author assisted in
      reaching consensus if there were any discrepancies. Similarly, risk of bias was
      assessed by two authors and verified by a third author. MAIN RESULTS: A total of
      12 trials (11 randomized controlled trials and one quasi-randomized trial) of 563
      people with HbSS, HbSC or HbSbetathal, aged six to 35 years old, were included in
      the review; the majority of participants were African-American. Interventions
      ranged from a total of one hour to weekly sessions for eight weeks and the post
      intervention assessments ranged from the end of the intervention period to 12
      months after completion. The heterogeneity of the included trials, which
      encompasses setting, inclusion and exclusion criteria, interventional method and
      time of assessment, ranged from 'not important' to 'moderate to substantial' for
      different review outcomes. The overall risk of bias was low for selective
      reporting, unclear for random sequence generation, allocation concealment,
      blinding of participants and blinding of outcome assessment. Incomplete outcome
      reporting and blinding of personnel showed mixed bias representations.Patient
      knowledge was assessed by four trials (160 participants) with moderate to
      substantial heterogeneity. There was evidence that educational programs improved
      patient knowledge, standardised mean difference 0.87 points (95% confidence
      interval 0.28 to 1.45, moderate quality evidence), which improved further when a
      trial with high bias was removed in a sensitivity analysis. Caregiver knowledge,
      reported in a single trial of 20 families, also showed an improvement,
      standardised mean difference 0.52 points (95% confidence interval 0.03 to 1.00,
      moderate quality evidence). The effect on patient knowledge was sustained at
      longer follow-up periods, whereas the effect on caregiver knowledge was not
      sustained.There were two primary outcomes related to the effectiveness of
      educational programs on the recognition of signs and symptoms of disease-related
      morbidity. No comparative data were reported for patients or caregivers (or both)
      recognising signs and symptoms leading to self-management. Data from two trials
      were analysed for the utilization of health services and showed no evidence of an
      effect, mean difference 0.33 (95% confidence interval -0.57 to 1.23, moderate
      quality evidence).With regard to the review's secondary outcomes, depression
      showed a statistically significant decline in intervention groups, standardised
      mean difference -0.66 points (95% confidence interval -1.18, to -0.14, moderate
      quality evidence). Adherence to treatment was not assessed in any of the
      identified trials. No effects of interventions were seen on coping, family
      relationships or health-related quality of life of patients.The quality of
      evidence was low for positive coping and moderate for child knowledge, healthcare
      utilization and depression. This suggests that further research is likely to have
      an important impact on our confidence in the estimate of effect and may change
      the estimates. AUTHORS' CONCLUSIONS: This review identifies important positive
      effects of educational interventions on improving patient knowledge of sickle
      cell disease and depression. Effects on patients' knowledge were maintained for
      longer than for caregivers. The effect on knowledge was significant but small and
      whether it offers any clinical benefit is uncertain. Significant factors limiting
      these effects could be trials being under powered as well as attrition rates.
      Effects were not statistically significant in assessments of secondary outcomes,
      possibly due to the paucity of the number of trials and patients and caregivers.
      Trials showed moderate to high heterogeneity which might impact the results. To
      better study effects on outcomes, further controlled trials are needed with
      rigorous attention given to improve recruitment and retention and to decrease
      bias. Predetermined protocols using similar measurements should be used across
      multiple sites.

PMID- 27711981
TI  - Assessing moderated mediation in linear models requires fewer confounding
      assumptions than assessing mediation.
AB  - It is well known from the mediation analysis literature that the identification
      of direct and indirect effects relies on strong no unmeasured confounding
      assumptions of no unmeasured confounding. Even in randomized studies the mediator
      may still be correlated with unobserved prognostic variables that affect the
      outcome, in which case the mediator's role in the causal process may not be
      inferred without bias. In the behavioural and social science literature very
      little attention has been given so far to the causal assumptions required for
      moderated mediation analysis. In this paper we focus on the index for moderated
      mediation, which measures by how much the mediated effect is larger or smaller
      for varying levels of the moderator. We show that in linear models this index can
      be estimated without bias in the presence of unmeasured common causes of the
      moderator, mediator and outcome under certain conditions. Importantly, one can
      thus use the test for moderated mediation to support evidence for mediation under
      less stringent confounding conditions. We illustrate our findings with data from
      a randomized experiment assessing the impact of being primed with social
      deception upon observer responses to others' pain, and from an observational
      study of individuals who ended a romantic relationship assessing the effect of
      attachment anxiety during the relationship on mental distress 2 years after the
      break-up.

PMID- 27711979
TI  - Innate immune responses in the ageing lung.
AB  - The world is undergoing an unprecedented shift in demographics, with the number
      of individuals over the age of 60 years projected to reach 2 billion or more by
      2050, representing 22% of the global population. Elderly people are at a higher
      risk for chronic disease and more susceptible to infection, due in part to age
      related dysfunction of the immune system resulting from low-grade chronic
      inflammation known as 'inflamm-ageing'. The innate immune system of older
      individuals exhibits a diminished ability to respond to microbial threats and
      clear infections, resulting in a greater occurrence of many infectious diseases
      in elderly people. In particular, the incidence of and mortality from lung
      infections increase sharply with age, with such infections often leading to worse
      outcomes, prolonged hospital stays and life-threatening complications, such as
      sepsis or acute respiratory distress syndrome. In this review, we highlight
      research on bacterial pneumonias and pulmonary viral infections and discuss age
      related changes in innate immunity that contribute to the higher rate of these
      infections in older populations. By understanding more clearly the innate immune
      defects in elderly individuals, we can design age-specific therapies to address
      lung infections in such a vulnerable population.

PMID- 27711983
TI  - Hot spots become cold spots: coevolution in variable temperature environments.
AB  - Antagonistic coevolution between hosts and parasites is a key process in the
      genesis and maintenance of biological diversity. Whereas coevolutionary dynamics
      show distinct patterns under favourable environmental conditions, the effects of
      more realistic, variable conditions are largely unknown. We investigated the
      impact of a fluctuating environment on antagonistic coevolution in experimental
      microcosms of Pseudomonas fluorescens SBW25 and lytic phage SBWPhi2. High
      frequency temperature fluctuations caused no deviations from typical
      coevolutionary arms race dynamics. However, coevolution was stalled during
      periods of high temperature under intermediate- and low-frequency fluctuations,
      generating temporary coevolutionary cold spots. Temperature variation affected
      population density, providing evidence that eco-evolutionary feedbacks act
      through variable bacteria-phage encounter rates. Our study shows that
      environmental fluctuations can drive antagonistic species interactions into and
      out of coevolutionary cold and hot spots. Whether coevolution persists or stalls
      depends on the frequency of change and the environmental optima of both
      interacting players.

PMID- 27711982
TI  - Association of Anticholinergic Burden with Cognitive Impairment and Health Care
      Utilization Among a Diverse Ambulatory Older Adult Population.
AB  - STUDY OBJECTIVE: To determine the association between Anticholinergic Cognitive
      Burden (ACB) score and both cognitive impairment and health care utilization
      among a diverse ambulatory older adult population. DESIGN: Retrospective cohort
      study. DATA SOURCE: Medication exposure and other clinical data were extracted
      from the Regenstrief Medical Record System (RMRS), and cognitive diagnosis was
      derived from a dementia screening and diagnosis study. PATIENTS: A total of 3344
      community-dwelling older adults (age 65 yrs and older) who were enrolled in a
      previously published dementia screening and diagnosis study; of these, 3127 were
      determined to have no cognitive impairment, and 217 were determined to have
      cognitive impairment. MEASUREMENTS AND MAIN RESULTS: The study followed a two
      phase screening and comprehensive neuropsychiatric examination to determine a
      cognitive diagnosis, which defined cognitive impairment as dementia or mild
      cognitive impairment. The ACB scale was used to identify anticholinergics
      dispensed in the 12 months prior to screening. A total daily ACB score was
      calculated by using pharmacy dispensing data from RMRS; each anticholinergic was
      multiplied by 1, 2, or 3 consistent with anticholinergic burden defined by the
      ACB scale. The sum of all ACB medications was divided by the number of days with
      any medication dispensed to achieve the total daily ACB score. Health care
      utilization included visits to inpatient, outpatient, and the emergency
      department, and it was determined by using visit data from the RMRS. The overall
      population had a mean age of 71.5 years, 71% were female, and 58% were African
      American. Each 1-point increase in mean total daily ACB score was associated with
      increasing risk of cognitive impairment (odds ratio [OR] 1.13, 95% confidence
      interval [CI] 1.004-1.27, p=0.043). Each 1-point increase in mean total daily ACB
      score increased the likelihood of inpatient admission (OR 1.11, 95% CI 1.02-1.29,
      p=0.014) and number of outpatient visits after adjusting for demographic
      characteristics, number of chronic conditions, and prior visit history (estimate
      0.382, standard error [SE] 0.113; p=0.001). The number of visits to the emergency
      department was also significantly different after similar adjustments (estimate
      0.046, SE 0.023, p=0.043). CONCLUSION: Increasing total ACB score was correlated
      with an increased risk for cognitive impairment and more frequent health care
      utilization. Future work should study interventions that safely reduce ACB and
      evaluate the impact on brain health and health care costs.

PMID- 27711984
TI  - Ordinary least squares regression is indicated for studies of allometry.
AB  - When it comes to fitting simple allometric slopes through measurement data,
      evolutionary biologists have been torn between regression methods. On the one
      hand, there is the ordinary least squares (OLS) regression, which is commonly
      used across many disciplines of biology to fit lines through data, but which has
      a reputation for underestimating slopes when measurement error is present. On the
      other hand, there is the reduced major axis (RMA) regression, which is often
      recommended as a substitute for OLS regression in studies of allometry, but which
      has several weaknesses of its own. Here, we review statistical theory as it
      applies to evolutionary biology and studies of allometry. We point out that the
      concerns that arise from measurement error for OLS regression are small and
      straightforward to deal with, whereas RMA has several key properties that make it
      unfit for use in the field of allometry. The recommended approach for researchers
      interested in allometry is to use OLS regression on measurements taken with low
      (but realistically achievable) measurement error. If measurement error is
      unavoidable and relatively large, it is preferable to correct for slope
      attenuation rather than to turn to RMA regression, or to take the expected amount
      of attenuation into account when interpreting the data.

PMID- 27711985
TI  - Dysfunction of Arabidopsis MACPF domain protein activates programmed cell death
      via tryptophan metabolism in MAMP-triggered immunity.
AB  - Plant immune responses triggered upon recognition of microbe-associated molecular
      patterns (MAMPs) typically restrict pathogen growth without a host cell death
      response. We isolated two Arabidopsis mutants, derived from accession Col-0, that
      activated cell death upon inoculation with nonadapted fungal pathogens. Notably,
      the mutants triggered cell death also when treated with bacterial MAMPs such as
      flg22. Positional cloning identified NSL1 (Necrotic Spotted Lesion 1) as a
      responsible gene for the phenotype of the two mutants, whereas nsl1 mutations of
      the accession No-0 resulted in necrotic lesion formation without pathogen
      inoculation. NSL1 encodes a protein of unknown function containing a putative
      membrane-attack complex/perforin (MACPF) domain. The application of flg22
      increased salicylic acid (SA) accumulation in the nsl1 plants derived from Col-0,
      while depletion of isochorismate synthase 1 repressed flg22-inducible lesion
      formation, indicating that elevated SA is needed for the cell death response.
      nsl1 plants of Col-0 responded to flg22 treatment with an RBOHD-dependent
      oxidative burst, but this response was dispensable for the nsl1-dependent cell
      death. Surprisingly, loss-of-function mutations in PEN2, involved in the
      metabolism of tryptophan (Trp)-derived indole glucosinolates, suppressed the
      flg22-induced and nsl1-dependent cell death. Moreover, the increased accumulation
      of SA in the nsl1 plants was abrogated by blocking Trp-derived secondary
      metabolite biosynthesis, whereas the nsl1-dependent hyperaccumulation of PEN2
      dependent compounds was unaffected when the SA biosynthesis pathway was blocked.
      Collectively, these findings suggest that MAMP-triggered immunity activates a
      genetically programmed cell death in the absence of the functional MACPF domain
      protein NSL1 via Trp-derived secondary metabolite-mediated activation of the SA
      pathway.

PMID- 27711987
TI  - Physical Microfabrication of Shape-Memory Polymer Systems via Bicomponent Fiber
      Spinning.
AB  - As emerging technologies continue to require diverse materials capable of
      exhibiting tunable stimuli-responsiveness, shape-memory materials are of
      considerable significance because they can change size and/or shape in
      controllable fashion upon environmental stimulation. Of particular interest,
      shape-memory polymers (SMPs) have secured a central role in the ongoing
      development of relatively lightweight and remotely deployable devices that can be
      further designed with specific surface properties. In the case of thermally
      activated SMPs, two functional chemical species must be present to provide (i) an
      elastic network capable of restoring the SMP to a previous strain state and (ii)
      switching elements that either lock-in or release a temporary strain at a well
      defined thermal transition. While these species are chemically combined into a
      single macromolecule in most commercially available SMPs, this work establishes
      that, even though they are physically separated across one or more
      polymer/polymer interfaces, their shape-memory properties are retained in melt
      spun bicomponent fibers. In the present study, we investigate the effects of
      fiber composition and cross-sectional geometry on both conventional and cold-draw
      shape memory, and report surprisingly high levels of strain fixity and recovery
      that generally improve upon strain cycling.

PMID- 27711986
TI  - Esophageal carcinoma: Ex vivo evaluation by high-spatial-resolution T2 -mapping
      MRI compared with histopathological findings at 3.0T.
AB  - PURPOSE: To prospectively determine the feasibility of T2 -mapping magnetic
      resonance imaging (MRI) to quantitatively describe the signal characteristics of
      the normal esophageal wall and assess the depth of esophageal wall invasion by
      carcinoma at 3.0T. MATERIALS AND METHODS: Thirty-two patient specimens, each
      having foci of carcinoma, were studied using 3.0T MR. Freehand regions of
      interest were placed to measure the T2 value of the normal esophageal layers and
      were compared with the regions of carcinoma. Three independent readers reviewed
      the MR images to evaluate the depth of carcinoma invasion; when the three
      radiologists could not fully agree with each other, the final stage was
      determined by consensus. The Games-Howell test was used to compare the difference
      between the normal esophageal layers and carcinoma. Spearman correlation
      coefficient analysis was used to compare the stage at MRI with that at
      histopathological analysis. The interobserver agreement was compared with Cohen's
      kappa. The sensitivity, specificity, and accuracy for detecting carcinoma
      invasion were calculated. RESULTS: The T2 values between the carcinoma and normal
      esophageal layers were different (all P < 0.01), except for the inner circular
      muscle (P = 0.511). The T2 value of each layer of the normal esophageal wall was
      also different from that of the adjacent layer (all P < 0.01). In 29 of 32
      lesions, the depth of the esophageal wall invasion determined by MR was
      consistent with the histopathological stage (r = 0.969, P < 0.001). The
      sensitivity, specificity, and accuracy were 80%, 96.3%, and 93.8%, respectively,
      for invasion into the mucosa; 77.8%, 95.7%, and 90.6%, respectively, for invasion
      into submucosa; 100%, 95.8%, and 96.9%, respectively, for invasion into
      muscularis propria; and 100%, 100%, and 100%, respectively, for invasion into the
      adventitia. CONCLUSION: T2 -mapping MR images obtained using a 3.0T MR scanner
      can be used to depict the precise histopathological layers of the esophageal wall
      clearly and provide excellent diagnostic accuracy for assessing esophageal
      carcinoma invasion. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN.
      RESON. IMAGING 2017;45:1609-1616.

PMID- 27711988
TI  - Status of Removable Dentures and Relationship with Oral Candida-Associated
      Factors in a Geriatric Population in Catalonia.
AB  - PURPOSE: Colonization by Candida is related to wearing a denture. How denture
      type, status, and maintenance play a role in determining Candida colonization
      remains unknown. This work evaluated removable denture status in an elderly
      population and explored the association between denture-related factors and oral
      Candida colonization as determined by systemic and local factors. MATERIALS AND
      METHODS: Socio-demographic, general health, and behavioral data and oral factors
      were registered by means of a questionnaire. Oral, dental, and denture-related
      factors were assessed by clinical examination, and yeasts were isolated from oral
      and denture specimens. Multiple logistic regression analysis was used to explore
      the relative relevance of risk factors. RESULTS: Overall, 52.4% of subjects used
      complete dentures in both lower and upper arches, and 90% of the prostheses were
      in good condition. Denture plaque index was high in most cases, and 75% of
      subjects had yeasts in their oral cavities. Oral Candida colonization was
      significantly associated with low saliva pH, sugar consumption, and the fault of
      a denture component; however, only sugar consumption was found to be an
      independent factor related with oral Candida colonization, showing an odds ratio
      of 3.04 in a multiple logistic regression model. CONCLUSIONS: Elderly people in
      this study used a complete denture in good condition, with a median age of 15
      years. Daily or weekly sugar consumption was found to be highly associated with
      oral colonization by Candida.

PMID- 27711989
TI  - Discordant ventriculo-arterial connections, or "transposition", are not
      necessarily an essential part of isomerism.

PMID- 27711991
TI  - Conformational study of tylosin A in water and full assignments of 1 H and 13 C
      spectra of tylosin A in D2 O and tylosin B in CDCl3.

PMID- 27711990
TI  - Identification of fungal candidates for asthma protection in a large population
      based study.
AB  - BACKGROUND: Exposure to molds has been related to asthma risk both positively and
      negatively, depending on the environmental setting. The pertinent results are
      based on generic markers or culturing methods although the majority of present
      fungi cannot be cultured under laboratory conditions. The aim of the present
      analysis was to assess environmental dust samples for asthma-protective fungal
      candidates with a comprehensive molecular technique covering also non-cultivable
      and non-viable fungi. METHODS: Mattress dust samples of 844 children from the
      GABRIELA study were analyzed by polymerase chain reaction-single-strand
      conformation polymorphism (PCR-SSCP) of the fungus-specific internal transcribed
      spacer (ITS) region. Known asthma candidate species were tested for their
      associations with asthma, and further gel positions were sought to explain the
      above. As a second, data-driven, analysis, we tested the association of each
      individual gel position with asthma. RESULTS: In the hypothesis-driven approach,
      Penicillium chrysogenum emerged with an odds ratio of 0.80 (95% confidence
      interval 0.66-0.96; p = 0.020). The effect size was changed by 39% toward the
      null when adjusting for the two bands 683 (DNA of Metschnikowia sp.,
      Aureobasidium spp.) and 978 (DNA of Epicoccum spp., Galactomyces spp., uncultured
      Penicillium). The data-driven approach yielded an additional band (containing DNA
      of Pseudotaeniolina globosa) with reduced risk of asthma (OR = 0.80 [0.66-0.96],
      p = 0.012). CONCLUSIONS: A large population-based study revealed several fungal
      taxa with inverse associations with childhood asthma. Molds produce a variety of
      bioactive compounds with detrimental but also beneficial immunoregulatory
      capacities, which renders them promising targets for further asthma research.

PMID- 27711992
TI  - ABI4 represses the expression of type-A ARRs to inhibit seed germination in
      Arabidopsis.
AB  - The plant hormone abscisic acid (ABA) plays a crucial role in regulating seed
      germination and post-germination growth. ABSCISIC ACID INSENSITIVE4 (ABI4), an
      APETALA2 (AP2)-type transcription factor, is required for the ABA-mediated
      inhibition of seed germination. Cytokinins promote seed germination and seedling
      growth by antagonizing ABA signaling. However, the interaction between ABA and
      cytokinin signaling during seed germination remains unclear. Here, we report that
      ABA signaling downregulates Arabidopsis response regulators (ARRs), a class of
      cytokinin-inducible genes, during seed germination and cotyledon greening. We
      found that the application of exogenous ABA repressed the expression of type-A
      ARRs in Arabidopsis seeds and seedlings. Among the type-A ARR family members, the
      expression of ARR6, ARR7 and ARR15 was upregulated in ABA-deficient mutants,
      indicating that the transcriptional inhibition of type-A ARRs requires the ABA
      signaling pathway. Single and multiple mutations of these ARRs resulted in
      increased ABA sensitivity during germination and cotyledon greening;
      overexpression of ARR7 or ARR15 led to an ABA-insensitive phenotype. These
      observations suggest that type-A ARRs inhibit the ABA response during seed
      germination and cotyledon greening. Further analysis showed that ABI4 negatively
      regulated the transcription of ARR6, ARR7 and ARR15 by directly binding to their
      promoters. Genetic analysis showed that loss-of-function mutations of ARR7 and
      ARR15 partially rescued the ABA insensitivity of abi4-1. Thus, this study
      revealed that ABI4 plays a key role in ABA and cytokinin signaling by inhibiting
      the transcription of type-A ARRs to inhibit seed germination and cotyledon
      greening.

PMID- 27711994
TI  - Methods and terminology used in cell-culture studies of low-dose effects of
      matrix constituents of polymer resin-based dental materials.
AB  - General comprehension of terms and confounding factors associated with in vitro
      experiments can maximize the potential of in vitro testing of substances. In this
      systematic review, we present an overview of the terms and methods used to
      determine low-dose effects of matrix constituents in polymer resin-based dental
      materials in cell-culture studies and discuss the findings in light of how they
      may influence the comprehension and interpretation of results. Articles published
      between 1996 and 2015 were identified by searches in the Scopus, Web of Science,
      MEDLINE, PubMed, and Embase databases using keywords associated with low-dose
      effects, polymer resin-based materials, in vitro parameters, and dental
      materials. Twenty-nine articles were included. Subtoxic (n = 11), sublethal (n =
      10), and nontoxic (n = 6) were the terms most commonly used to describe the low
      dose effects of methacrylates. However, definition of terms varied. Most (82%)
      studies employed only one method to define the exposure scenario, and no
      agreement was seen between studies on the use of solvents. Prophylactic use of
      antibiotics was widespread, and mycoplasma screening was not reported. In
      conclusion, cell-culture conditions and tests used to define exposure scenarios
      have changed little in the last decades, despite development in recommendations.
      Nomenclature alignment is needed for a better understanding of possible
      biohazards of methacrylates.

PMID- 27711993
TI  - High sensitivity of spontaneous spike frequency to sodium leak current in a
      Lymnaea pacemaker neuron.
AB  - The spontaneous rhythmic firing of action potentials in pacemaker neurons depends
      on the biophysical properties of voltage-gated ion channels and background leak
      currents. The background leak current includes a large K+ and a small Na+
      component. We previously reported that a Na+ -leak current via U-type channels is
      required to generate spontaneous action potential firing in the identified
      respiratory pacemaker neuron, RPeD1, in the freshwater pond snail Lymnaea
      stagnalis. We further investigated the functional significance of the background
      Na+ current in rhythmic spiking of RPeD1 neurons. Whole-cell patch-clamp
      recording and computational modeling approaches were carried out in isolated
      RPeD1 neurons. The whole-cell current of the major ion channel components in
      RPeD1 neurons were characterized, and a conductance-based computational model of
      the rhythmic pacemaker activity was simulated with the experimental measurements.
      We found that the spiking rate is more sensitive to changes in the Na+ leak
      current as compared to the K+ leak current, suggesting a robust function of Na+
      leak current in regulating spontaneous neuronal firing activity. Our study
      provides new insight into our current understanding of the role of Na+ leak
      current in intrinsic properties of pacemaker neurons.

PMID- 27711995
TI  - Efficacy and safety of superficial cryotherapy for alopecia areata: A
      retrospective, comprehensive review of 353 cases over 22 years.
AB  - Alopecia areata (AA) affects anagen hair follicles, resulting in non-scarring
      hair loss. Since introduced by Huang et al., superficial cryotherapy has been
      accepted as a considerable primary therapeutic modality for AA. The aim of this
      study was to objectively clarify the therapeutic efficacy and safety of
      superficial hypothermic cryotherapy for treatment of AA. Medical records of 353
      patients from 1993 to 2014 were retrospectively analyzed. According to the
      response to the superficial cryotherapy, patients were categorized into four
      groups: "marked", "partial", "poor" and "no recovery". The marked and partial
      recovery groups were considered as responders. The proportions of the responders
      among patient subgroups which were defined by various patients, disease, and
      treatment factors were compared. Of the patients, 60.9% were classified as
      responders after 3 months of superficial hypothermic cryotherapy. The proportion
      of the responders were higher when the treatment interval was 2 weeks or less and
      in the incipient disease stage, with statistical significance. No severe side
      effects other than mild pain and pruritus were reported. In conclusion,
      superficial cryotherapy is an effective and safe therapeutic modality for AA.
      Especially when the treatment interval is 2 weeks or less and in the first
      occurrence of the disease, the therapeutic outcome is superior.

PMID- 27711996
TI  - Editorial: It is about time to stop misusing the P-value?

PMID- 27711997
TI  - Overcoming Autofluorescence: Long-Lifetime Infrared Nanoparticles for Time-Gated
      In Vivo Imaging.
AB  - The always present and undesired contribution of autofluorescence is here
      completely avoided by combining a simple time gating technology with long
      lifetime neodymium doped infrared-emitting nanoparticles.

PMID- 27711998
TI  - VTA dopamine neuron plasticity - the unusual suspects.
AB  - Dopamine neurons in the ventral tegmental area (VTA) are involved in a variety of
      physiological and pathological conditions, ranging from motivated behaviours to
      substance use disorders. While many studies have shown that these neurons can
      express plasticity at excitatory and inhibitory synapses, little is known about
      how inhibitory inputs and glial activity shape the output of DA neurons and
      therefore, merit greater discussion. In this review, we will attempt to fill in a
      bit more of the puzzle, with a focus on inhibitory transmission and astrocyte
      function. We summarize the findings within the VTA as well as observations made
      in other brain regions that have important implications for plasticity in general
      and should be considered in the context of DA neuron plasticity.

PMID- 27712001
TI  - Alveolar ridge preservation after tooth extraction: a Bayesian Network meta
      analysis of grafting materials efficacy on prevention of bone height and width
      reduction.
AB  - AIMS: To conduct a traditional meta-analysis and a Bayesian Network meta-analysis
      to synthesize the information coming from randomized controlled trials on
      different socket grafting materials and combine the resulting indirect evidence
      in order to make inferences on treatments that have not been compared directly.
      MATERIALS AND METHODS: RCTs were identified for inclusion in the systematic
      review and subsequent statistical analysis. Bone height and width remodelling
      were selected as the chosen summary measures for comparison. First, a series of
      pairwise meta-analyses were performed and overall mean difference (MD) in mm with
      95% CI was calculated between grafted versus non-grafted sockets. Then, a
      Bayesian Network meta-analysis was performed to draw indirect conclusions on
      which grafting materials can be considered most likely the best compared to the
      others. RESULTS: From the six included studies, seven comparisons were obtained.
      Traditional meta-analysis showed statistically significant results in favour of
      grafting the socket compared to no-graft both for height (MD 1.02, 95% CI 0.44
      1.59, p value < 0.001) than for width (MD 1.52 95% CI 1.18-1.86, p value
      <0.000001) remodelling. Bayesian Network meta-analysis allowed to obtain a rank
      of intervention efficacy. CONCLUSIONS: On the basis of the results of the present
      analysis, socket grafting seems to be more favourable than unassisted socket
      healing. Moreover, Bayesian Network meta-analysis indicates that freeze-dried
      bone graft plus membrane is the most likely effective in the reduction of bone
      height remodelling. Autologous bone marrow resulted the most likely effective
      when width remodelling was considered. Studies with larger samples and less risk
      of bias should be conducted in the future in order to further strengthen the
      results of this analysis.

PMID- 27712000
TI  - Redox-Neutral Aromatization of Cyclic Amines: Mechanistic Insights and Harnessing
      of Reactive Intermediates for Amine alpha- and beta-C-H Functionalization.
AB  - Cyclic amines such as pyrrolidine and piperidine are known to undergo
      condensations with aldehydes to furnish pyrrole and pyridine derivatives,
      respectively. A combined experimental and computational study provides detailed
      insights into the mechanism of pyrrole formation. A number of reactive
      intermediates (e.g., azomethine ylides, conjugated azomethine ylides, enamines)
      were intercepted, outlining strategies for circumventing aromatization as a
      valuable pathway for amine C-H functionalization.

PMID- 27712002
TI  - Multi-parameter machine learning approach to the neuroanatomical basis of
      developmental dyslexia.
AB  - Despite decades of research, the anatomical abnormalities associated with
      developmental dyslexia are still not fully described. Studies have focused on
      between-group comparisons in which different neuroanatomical measures were
      generally explored in isolation, disregarding potential interactions between
      regions and measures. Here, for the first time a multivariate classification
      approach was used to investigate grey matter disruptions in children with
      dyslexia in a large (N = 236) multisite sample. A variety of cortical
      morphological features, including volumetric (volume, thickness and area) and
      geometric (folding index and mean curvature) measures were taken into account and
      generalizability of classification was assessed with both 10-fold and leave-one
      out cross validation (LOOCV) techniques. Classification into control vs. dyslexic
      subjects achieved above chance accuracy (AUC = 0.66 and ACC = 0.65 in the case of
      10-fold CV, and AUC = 0.65 and ACC = 0.64 using LOOCV) after principled feature
      selection. Features that discriminated between dyslexic and control children were
      exclusively situated in the left hemisphere including superior and middle
      temporal gyri, subparietal sulcus and prefrontal areas. They were related to
      geometric properties of the cortex, with generally higher mean curvature and a
      greater folding index characterizing the dyslexic group. Our results support the
      hypothesis that an atypical curvature pattern with extra folds in left
      hemispheric perisylvian regions characterizes dyslexia. Hum Brain Mapp 38:900
      908, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27712003
TI  - Photoprotective and antioxidant responses to light spectrum and intensity
      variations in the coastal diatom Skeletonema marinoi.
AB  - Photosynthesis is known to produce reactive oxygen species together with the
      transformation of light into biochemical energy. To fill the gap of the knowledge
      on the protective antioxidant network of microalgae, a series of experiments to
      explore the role of spectral composition and intensity of light in the modulation
      of the photodefence mechanisms developed by the coastal diatom Skeletonema
      marinoi were performed. The modulation of the total phenolic content, ascorbic
      acid and the enzymes glutathione reductase, catalase, ascorbate peroxidase and
      superoxide dismutase together with xanthophyll cycle and non-photochemical
      quenching in response to variations in the light environment were analysed. Most
      of the enzymes' activity was promptly affected by the red light. Yet, the
      monochromatic high intensity blue light enhanced the synthesis of total phenolic
      content and ascorbic acid in parallel to the xanthophyll cycle activity. This
      study reveals the dual effects of spectral composition and intensity of light on
      the modulation of photoprotective mechanisms. Diatoms developed a complementary
      and/or alternative tuning processes to cope with the variable light environment
      they experience in the water column. They also provided valuable insights into
      light manipulation regimes for diatom cultivation that will help to maximize
      production of bioactive molecules.

PMID- 27712005
TI  - Glyoxal measurement with a proton transfer reaction time of flight mass
      spectrometer (PTR-TOF-MS): characterization and calibration.
AB  - We examine the potential for PTR-TOF-MS systems to quantitatively measure glyoxal
      in ambient air by characterizing the response of the instrument to a dilute
      glyoxal sample, calibrating the system as a function of humidity. The
      concentration of glyoxal in a sample air-stream was measured with an UV
      absorption spectrometer in parallel to a PTR-TOF-MS. This calibration
      demonstrated that the PTR-TOF-MS has a relatively low sensitivity to glyoxal
      particularly at high humidity. Extensive fragmentation of glyoxal to formaldehyde
      was observed. This behaviour not only desensitizes PTR-MS system to glyoxal; it
      may also pose a problem to the quantification of formaldehyde. (c) 2016 The
      Authors. Journal of Mass Spectrometry Published by John Wiley & Sons Ltd.

PMID- 27712004
TI  - Pulmonary vascular inflammation: effect of TLR signalling on angiopoietin/TIE
      regulation.
AB  - Increased pulmonary vascular resistance is a critical complication in sepsis.
      Toll-like receptor (TLR) as well as angiopoietin (ANG) signalling both contribute
      to the emergence of pulmonary arterial hypertension. We hypothesized that TLR
      stimulation by bacterial ligands directly affects expression and secretion of
      ligands and receptors of the angiopoietin/TIE axis. Microvascular endothelial
      (HPMEC) and smooth muscle cells (SMC) of pulmonary origin were incubated with
      thrombin and with ligands for TLR2, -4, -5, and -9. Expression and secretion of
      ANG1, -2, TIE2 and IL-8 were determined using quantitative real-time PCR and
      ELISA. TLR stimulation had no impact either on the expression of ANG2 and TIE2 in
      HPMEC or on that of ANG1 in SMC. However, overall levels of both released ANG1
      and -2 were halved upon stimulation with the TLR9 ligand CpG, and ANG2 release
      was significantly enhanced by TLR4 activation when initially provoked by
      sequentially performed stimulation. Furthermore, enhanced ANG2 activity increased
      endothelial permeability, as demonstrated in an in vitro transwell assay. We
      conclude that sole TLR stimulation by bacterial ligands plays no significant role
      for altered expression and secretion of ANG1, -2 and TIE2 in human pulmonary
      vascular cells. The interplay between various stimuli is required to induce
      imbalances between ANG1 and -2.

PMID- 27712006
TI  - Is radiotherapy the best option for treating hepatocellular carcinoma with portal
      vein tumour thrombosis?

PMID- 27712007
TI  - A Cooperative Strategy for the Highly Selective Intermolecular Oxycarbonylation
      Reaction of Alkenes using a Palladium Catalyst.
AB  - A novel method for intermolecular functionalization of terminal and internal
      alkenes has been designed. The electrophilic reagent, hypervalent iodine, plays a
      key role in this process by activating the alkene C=C bond for nucleophilic
      addition of the palladium catalyst. This process generates an iodonium-containing
      palladium species which undergoes CO insertion. The new approach, intermolecular
      oxycarbonylaton reactions of alkenes, has been achieved and carried out under
      mild reaction conditions to produce the corresponding beta-oxycarbonylic acids
      with excellent efficiencies and levels of regio- and diastereoselectivity.

PMID- 27711999
TI  - NMR Hyperpolarization Techniques of Gases.
AB  - Nuclear spin polarization can be significantly increased through the process of
      hyperpolarization, leading to an increase in the sensitivity of nuclear magnetic
      resonance (NMR) experiments by 4-8 orders of magnitude. Hyperpolarized gases,
      unlike liquids and solids, can often be readily separated and purified from the
      compounds used to mediate the hyperpolarization processes. These pure
      hyperpolarized gases enabled many novel MRI applications including the
      visualization of void spaces, imaging of lung function, and remote detection.
      Additionally, hyperpolarized gases can be dissolved in liquids and can be used as
      sensitive molecular probes and reporters. This Minireview covers the fundamentals
      of the preparation of hyperpolarized gases and focuses on selected applications
      of interest to biomedicine and materials science.

PMID- 27712008
TI  - Overexpression of a tomato miR171 target gene SlGRAS24 impacts multiple
      agronomical traits via regulating gibberellin and auxin homeostasis.
AB  - In Arabidopsis, the miR171-GRAS module has been clarified as key player in
      meristem maintenance. However, the knowledge about its role in fruit crops like
      tomato (Solanum lycopersicum) remains scarce. We previously identified tomato
      SlGRAS24 as a target gene of Sly-miR171. To study the role of this probable
      transcription factor, we generated transgenic tomato plants underexpressing
      SlGRAS24, overexpressing SlGRAS24, overexpressing Sly-miR171 and expressing beta
      glucuronidase (GUS) under the SlGRAS24 promoter (proSlGRAS24-GUS). Plants
      overexpressing SlGRAS24 (SlGRAS24-OE) had pleiotropic phenotypes associated with
      multiple agronomical traits including plant height, flowering time, leaf
      architecture, lateral branch number, root length, fruit set and development. Many
      GA/auxin-related genes were down-regulated and altered responsiveness to
      exogenous IAA/NAA or GA3 application was observed in SlGRAS24-OE seedlings.
      Moreover, compromised fruit set and development in SlGRAS24-OE was also observed.
      These newly identified phenotypes for SlGRAS24 homologs in tomato were later
      proved to be caused by impaired pollen sacs and fewer viable pollen grains. At
      anthesis, the comparative transcriptome results showed altered expression of
      genes involved in pollen development and hormone signalling. Taken together, our
      data demonstrate that SlGRAS24 participates in a series of developmental
      processes through modulating gibberellin and auxin signalling, which sheds new
      light on the involvement of hormone crosstalk in tomato development.

PMID- 27712009
TI  - Broad phylogeny and functionality of cellulosomal components in the bovine rumen
      microbiome.
AB  - The cellulosome is an extracellular multi-enzyme complex that is considered one
      of the most efficient plant cell wall-degrading strategies devised by nature. Its
      unique modular architecture, achieved by high affinity and specific interaction
      between protein modules (cohesins and dockerins) enables formation of various
      enzyme combinations. Extensive research has been dedicated to the mechanistic
      nature of the cellulosome complex. Nevertheless, little is known regarding its
      distribution and abundance among microbes in natural plant fibre-rich
      environments. Here, we explored these questions in bovine rumen microbial
      communities, specialized in efficient degradation of lignocellulosic plant
      material. We bioinformatically screened for cellulosomal modules in this complex
      environment using a previously published ultra-deep fibre-adherent rumen
      metagenome. Intriguingly, a large portion of the functions of the dockerin
      containing proteins were related to alternative biological processes, and not
      necessarily to the classic fibre degradation function. Our analysis was
      experimentally validated by characterizing specific interactions between selected
      cohesins and dockerins and revealed that cellulosome is a more generalized
      strategy used by diverse bacteria, some of which were not previously associated
      with cellulosome production. Remarkably, our results provide additional proof of
      similarity among rumen microbial communities worldwide. This study suggests a
      broader and widespread role for the cellulosomal machinery in nature.

PMID- 27712010
TI  - Hepatic manifestations of inflammatory bowel diseases.
AB  - Inflammatory bowel diseases are associated with various hepatobiliary disorders,
      reported both in Crohn's disease and ulcerative colitis. They may occur at any
      moment in the natural course of the disease. The prevalence of liver dysfunction
      rises from 3% to 50% accordingly to definitions used in different studies. Fatty
      liver is considered as the most common hepatobiliary complication in inflammatory
      bowel diseases while primary sclerosing cholangitis is the most specific one.
      Less frequently, inflammatory bowel diseases-associated hepatobiliary disorders
      include: autoimmune hepatitis/ primary sclerosing cholangitis overlap syndrome,
      IgG4-associated cholangiopathy, primary biliary cholangitis, hepatic amyloidosis,
      granulomatous hepatitis, cholelithiasis, portal vein thrombosis and liver
      abscess. The spectrum of these manifestations varies according to the type of
      inflammatory bowel diseases. Treatments of inflammatory bowel diseases may cause
      liver toxicity, although incidence of serious complications remains low. However,
      early diagnosis of drug-induced liver injury is of major importance as it affects
      future clinical management. When facing abnormal liver tests, clinicians should
      undertake a full diagnostic work-up in order to determine whether the hepatic
      abnormalities are related to the inflammatory bowel diseases or not. Management
      of hepatic manifestations in inflammatory bowel diseases usually involves both
      hepatologists and gastroenterologists because of the complexity of some
      situations.

PMID- 27712011
TI  - Theory of Ultralong-Range Rydberg Molecule Formation Incorporating Spin-Dependent
      Relativistic Effects: Cs(6s)-Cs(np) as Case Study.
AB  - We calculate vibrational spectra of ultralong-range Cs(32p) Rydberg molecules
      that form in an ultracold gas of Cs atoms. We account for the partial-wave
      scattering of the Rydberg electrons from the Cs perturber atoms by including the
      full set of spin-resolved 1,3 SJ and 1,3 PJ scattering phase shifts, and allow
      for the mixing of singlet (S=0) and triplet (S=1) spin states through Rydberg
      electron spin-orbit and ground state electron hyperfine interactions. Excellent
      agreement with observed data in Sabetamannshausen et al. [Phys. Rev. Lett. 2015,
      113, 133201] in line positions and profiles is obtained. We also determine the
      spin-dependent permanent electric dipole moments for these molecules. This is the
      first such calculation of ultralong-range Rydberg molecules for which all of the
      relativistic contributions are accounted.

PMID- 27712012
TI  - Impulsive Collision Dynamics of CO Super Rotors from an Optical Centrifuge.
AB  - We report state-resolved collision dynamics for CO molecules prepared in an
      optical centrifuge and measured with high-resolution transient IR absorption
      spectroscopy. Time-resolved polarization-sensitive measurements of excited CO
      molecules in the J=29 rotational state reveal that the oriented angular momentum
      of CO rotors is relaxed by impulsive collisions. The translational energy gains
      for molecules in the initial plane of rotation are threefold larger than for
      randomized angular momentum orientations, indicating the presence of anisotropic
      kinetic energy. The transient data show enhanced population for CO molecules in
      the initial plane of rotation immediately following the optical centrifuge pulse.
      A comparison with previous CO2 super rotor studies illustrates the behavior of
      molecular gyroscopes; spatial reorientation of CO2 J=76 rotors takes
      substantially longer than that for CO J=29 rotors, despite similarities in
      classical rotational period and rotational energy gap. High-resolution transient
      IR absorption measurements of the CO J=29-39 rotational states show that the
      collisional depopulation rates increase with J quantum number.

PMID- 27712013
TI  - An in vitro comparison of the effects of voluven (6% hydroxyethyl starch 130/0.4)
      and hespan (6% hydroxyethyl starch 670/0.75) on measures of blood coagulation in
      canine blood.
AB  - OBJECTIVE: To assess primary and secondary hemostasis following in vitro dilution
      of canine whole blood (WB) with hydroxyethyl starch (HES) 130/0.4 and HES
      670/0.75. DESIGN: In vitro experimental study. SETTING: Private practice,
      teaching hospital. ANIMALS: Twenty-five healthy dogs. INTERVENTIONS: Each dog
      underwent venipuncture and 18 mL of venous blood was sampled once. MEASUREMENTS
      AND MAIN RESULTS: Collected blood was separated in 4 aliquots. Aliquot A served
      as baseline sample. The remaining tubes of WB were diluted with 0.9% saline, HES
      670/0.75 and HES 130/0.4 at a ratio of 1:5.5. Dilutional effects were evaluated
      using prothrombin time (PT), activated partial thromboplastin time (aPTT), packed
      cell volume (PCV), thromboelastography (TEG), and platelet closure time (Ct),
      which was measured using a platelet function analyzer (PFA). Clot strength (ie, G
      value) was calculated from measured TEG values. Significant increases in PT (P <
      0.05) and aPTT (P < 0.05) were documented following WB dilution with saline.
      Dilution of WB with HES 670/0.75 and HES 130/0.4 resulted in significant
      hypocoagulable changes in K, MA and G (P < 0.05) compared to baseline and saline.
      When comparing saline to HES 670/0.75, both R and K values were significantly
      increased (P < 0.05). K value was significantly increased (P < 0.05) when
      comparing baseline to HES 130/0.4 and HES 670/0.75. Ct (P < 0.05) was
      significantly prolonged after WB dilution with HES solutions but not after
      saline. CONCLUSIONS: Dilution of WB with HES 670/0.75 and HES 130/0.4 resulted in
      changes in primary and secondary hemostasis. Although there were small
      differences between saline and HES 670/0.75, no differences between HES solutions
      were evident in this small study. This may suggest there would be minimal
      increases in bleeding risk when either solution is administered to dogs at low
      doses. Clinical relevance of our findings requires further investigation.

PMID- 27712014
TI  - Generation of a NK1R-CreER knockin mouse strain to study cells involved in
      Neurokinin 1 Receptor signaling.
AB  - The Neurokinin 1 Receptor (NK1R), which binds Substance P, is expressed in
      discrete populations of neurons throughout the nervous system, where it has
      numerous roles including the modulation of pain and affective behaviors. Here, we
      report the generation of a NK1R-CreER knockin allele, in which CreERT2 replaces
      the coding sequence of the TACR1 gene (encoding NK1R) in order to gain genetic
      access to these cells. We find that the NK1R-CreER allele mediates recombination
      in many regions of the nervous system that are important in pain and anxiety
      including the amygdala, hypothalamus, frontal cortex, raphe nucleus, and dorsal
      horn of the spinal cord. Other cell types that are labeled by this allele include
      amacrine cells in the retina and fibroblasts in the skin. Thus, the NK1R-CreER
      mouse line is a valuable new tool for conditional gene manipulation enabling the
      visualization and manipulation of cells that express NK1R.

PMID- 27712016
TI  - Post-transplant blood transfusions and pediatric renal allograft outcomes.
AB  - The association of blood transfusions with GS after pediatric KTx is unclear. We
      retrospectively analyzed blood transfusions post-KTx and subsequent outcomes.
      Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our
      center. Recipient demographics, outcomes and transfusion data were collected. Cox
      regression with post-KTx blood transfusion as a time-dependent covariate was
      performed to model the impact of blood transfusion on outcomes. Of the 208 (44%)
      that were transfused, 39% had transfusion <1 month post-KTx; 48% >12 months.
      Transfused and non-transfused recipients were not significantly different. In
      univariate and multivariate analyses, there was no difference between transfused
      and non-transfused recipient patient survival, antibody-mediated and ACR, and DSA
      free survival. Transfusions <1 month post-KTx did not impact DCGS (P=NS).
      Patients transfused >12 months post-KTx had significantly lower 12 month eGFR
      (compared to non-transfused) and worse subsequent DCGS. Post-KTx blood
      transfusions have increased in pediatric KTx over time but have no negative
      association with rejection or DSA production. DCGS is unaffected by transfusion
      within first month. Transfusions after the first year occur in patients with more
      advanced chronic kidney disease and are associated with significantly worse DCGS.

PMID- 27712015
TI  - Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type
      KRAS colorectal cancer-WJOG 6210G.
AB  - This randomized phase II trial compared panitumumab plus fluorouracil,
      leucovorin, and irinotecan (FOLFIRI) with bevacizumab plus FOLFIRI as second-line
      chemotherapy for wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC)
      and to explore the values of oncogenes in circulating tumor DNA (ctDNA) and serum
      proteins as predictive biomarkers. Patients with WT KRAS exon 2 mCRC refractory
      to first-line chemotherapy containing oxaliplatin and bevacizumab were randomly
      assigned to panitumumab plus FOLFIRI or bevacizumab plus FOLFIRI. Of 121 randomly
      assigned patients, 117 were eligible. Median overall survival (OS) for
      panitumumab plus FOLFIRI and bevacizumab plus FOLFIRI were 16.2 and 13.4 months
      [hazard ratio (HR), 1.16; 95% CI, 0.76-1.77], respectively. Progression-free
      survival (PFS) was also similar (HR, 1.14; 95% CI, 0.78-1.66). KRAS, NRAS, and
      BRAF status using ctDNA was successfully examined in 109 patients, and mutations
      were identified in 19 patients (17.4%). Panitumumab plus FOLFIRI showed favorable
      survival compared with bevacizumab plus FOLFIRI in WT patients and unfavorable
      survival in those with mutations (P for interaction = 0.026 in OS and 0.054 in
      PFS). OS with bevacizumab plus FOLFIRI was better than panitumumab plus FOLFIRI
      in patients with high serum vascular endothelial growth factor-A (VEGF-A) levels
      and worse in those with low levels (P for interaction = 0.016). Second-line
      FOLFIRI plus panitumumab and FOLFIRI plus bevacizumab showed a similar efficacy
      in patients with WT KRAS exon 2 mCRC. RAS and BRAF mutation in ctDNA could be a
      negative predictive marker for panitumumab.

PMID- 27712018
TI  - Prevalence of hair shedding among women.
AB  - Hair shedding in female patients is a frequent complaint in dermatological,
      endocrinological, and gynecological consults. Previously, the Sinclair Hair
      Shedding Scale was developed to assess normal versus excessive hair shedding in
      female pattern hair loss (FPHL) subjects. However, the prevalence of hair
      shedding in females not suffering from FPHL is unknown. To gain better
      understanding of hair shedding in the general population, we recruited 300
      subjects visiting a public hospital for conditions other than alopecia. Of the
      300 subjects recruited, 263 did not suffer from FPHL. Among those subjects,
      approximately 40% reported experiencing excessive hair shedding (as defined by
      the Sinclair Hair Shedding Scale) on hair washing days. In comparison, in our
      subject population, approximately 60% of subjects with FPHL reported excessive
      hair shedding on hair washing days. To best of our knowledge, this is the first
      study to quantify the prevalence of hair shedding in women. While, no treatment
      currently exists for this condition, we hope that this study would encourage
      physicians and researchers to address this frequent concern.

PMID- 27712017
TI  - Real life Egyptian experience of efficacy and safety of Simeprevir/Sofosbuvir
      therapy in 6211 chronic HCV genotype IV infected patients.
AB  - BACKGROUND & AIMS: Major changes have emerged during the last few years in the
      therapy of chronic HCV. Several direct acting antiviral agents have been
      developed showing potent activity with higher rates of sustained virological
      response, even in difficult-to-treat patients. This study explores real life
      experience concerning efficacy, safety and possible predictors of response for
      the first cohort of Egyptian patients with chronic HCV genotype IV treated with
      Sofosbuvir/Simprevir combination therapy. METHODS: This real life study recruited
      the first (6211) chronic HCV genotype IV Egyptian patients, who received
      antiviral therapy in viral hepatitis specialized treatment centres affiliated to
      the National committee for control of viral hepatitis. All enrolled patients
      received 12 weeks course of daily combination of sofosbuvir (400 mg) and
      simeprevir (150 mg). Patients were closely monitored for treatment safety and
      efficacy. RESULTS: Overall sustained virological response 12 rate was 94.0% while
      the end of treatment response rate was 97.6%. sustained virological response 12
      rates in easy and difficult-to-treat groups were 96% and 93% respectively.
      Univariate and multivariate logistic regression analysis revealed significant
      association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with
      treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to
      liver cell failure adverse events or SAEs leading to treatment discontinuation
      occurred in 97 patients (1.6%). CONCLUSION: Sofosbuvir/Simeprevir combination is
      an effective and well tolerated regimen for patients with chronic HCV genotype
      IV.

PMID- 27712019
TI  - Highly Efficient Cooperative Catalysis by CoIII (Porphyrin) Pairs in
      Interpenetrating Metal-Organic Frameworks.
AB  - A series of porous twofold interpenetrated In-CoIII (porphyrin) metal-organic
      frameworks (MOFs) were constructed by in situ metalation of porphyrin bridging
      ligands and used as efficient cooperative catalysts for the hydration of terminal
      alkynes. The twofold interpenetrating structure brings adjacent CoIII
      (porphyrins) in the two networks parallel to each other with a distance of about
      8.8 A, an ideal distance for the simultaneous activation of both substrates in
      alkyne hydration reactions. As a result, the In-CoIII (porphyrin) MOFs exhibit
      much higher (up to 38 times) catalytic activity than either homogeneous catalysts
      or MOF controls with isolated CoIII (porphyrin) centers, thus highlighting the
      potential application of MOFs in cooperative catalysis.

PMID- 27712020
TI  - Anti-PD-L1 treatment enhances antitumor effect of everolimus in a mouse model of
      renal cell carcinoma.
AB  - Immunotherapy based on blockade of the programmed death-1 (PD-1)/programmed death
      ligand 1 (PD-L1) axis has shown promising clinical activity for renal cell
      carcinoma (RCC) patients; however, the most effective use of these agents in
      combination with conventional targeted therapy remains to be resolved. Here we
      evaluated the therapeutic efficacy of the combination of the mTOR inhibitor
      everolimus (EVE) and anti-PD-L1 using an immunocompetent mouse model of RCC. We
      first assessed the in vitro effect of EVE on PD-L1 expression in the human 786-O
      and mouse RENCA RCC cell lines and found that EVE upregulated PD-L1 expression in
      these RCC cell lines. We then treated RENCA tumor-bearing mice with EVE and found
      that PD-L1 expression was also increased in tumor cells after EVE treatment. To
      determine the antitumor effects of EVE alone, anti-PD-L1 alone, and EVE in
      combination with anti-PD-L1, we evaluated their antitumor effects on RENCA tumor
      bearing mice. A significant decrease in the tumor burden was observed in the EVE
      alone but not in the anti-PD-L1 alone treatment group compared with the control
      group. Importantly, the combination of EVE with anti-PD-L1 significantly reduced
      tumor burden compared with the EVE alone treatment, increasing tumor infiltrating
      lymphocytes (TILs) and the ratio of cytotoxic CD8+ T cells to TILs. The results
      of the present study demonstrated that anti-PD-L1 treatment enhanced the
      antitumor effect of EVE in a mouse model, supporting a direct translation of this
      combination strategy to the clinic for the treatment of RCC.

PMID- 27712021
TI  - Bronchoscopy assessment of acute respiratory failure in interstitial lung
      disease.
AB  - BACKGROUND AND OBJECTIVE: Acute respiratory failure (ARF) in patients with
      interstitial lung disease (ILD) is associated with significant morbidity and
      mortality. Recommended assessment for acute exacerbation (AE) of ILD includes
      exclusion of secondary causes via fibreoptic bronchoscopy. Our aim is to assess
      the role of bronchoscopy during ARF-ILD. METHODS: Consecutive ILD patients (2002
      2014) hospitalized with ARF who underwent bronchoscopy were included. Baseline
      demographics, underlying ILD diagnoses and presenting clinical features were
      reviewed. Characteristics of bronchoscopy including diagnostic findings,
      management and complications were collated. RESULTS: One hundred and six patients
      accounted for 119 unique bronchoscopies. Sixteen (13%) were abnormal (12
      infections and 4 haemorrhages). Baseline presenting clinical features did not
      differ between those with and without abnormal findings. About half were
      performed in an intensive care unit (ICU) (53%), with 25% of bronchoscopies
      performed in a general floor setting resulting in ICU transfer; 71% of whom
      resulted in immediate mechanical ventilation. Overall management of ARF in those
      with positive bronchoscopy findings was similar to those without, resulting in
      similar in-hospital mortality. CONCLUSION: Bronchoscopy in the clinical
      assessment of ARF-ILD is often performed with only a 13% yield in this large
      retrospective cohort. As management and in-hospital mortality were similar,
      routine diagnostic bronchoscopy in ARF-ILD should be further studied given its
      low yield and high procedural risk.

PMID- 27712022
TI  - Anions Stabilize Each Other inside Macrocyclic Hosts.
AB  - Contrary to the simple expectations from Coulomb's law, Weinhold proposed that
      anions can stabilize each other as metastable dimers, yet experimental evidence
      for these species and their mutual stabilization is missing. We show that two
      bisulfate anions can form such dimers, which stabilize each other with self
      complementary hydrogen bonds, by encapsulation inside a pair of cyanostar
      macrocycles. The resulting 2:2 complex of the bisulfate homodimer persists across
      all states of matter, including in solution. The bisulfate dimer's OH???O
      hydrogen bonding is seen in a 1 H NMR peak at 13.75 ppm, which is consistent with
      borderline-strong hydrogen bonds.

PMID- 27712023
TI  - First Examples of de Vries-like Smectic A to Smectic C Phase Transitions in Ionic
      Liquid Crystals.
AB  - In ionic liquid crystals, the orthogonal smectic A phase is the most common phase
      whereas the tilted smectic C phase is rather rare. We present a new study with
      five novel ionic liquid crystals exhibiting both a smectic A as well as the rare
      smectic C phase. Two of them have a phenylpyrimidine core whereas the other three
      are imidazolium azobenzenes. Their phase sequences and tilt angles were studied
      by polarizing microscopy and their temperature-dependent layer spacing as well as
      their translational and orientational order parameters were studied by X-ray
      diffraction. The X-ray tilt angles derived from X-ray studies of the layer
      contraction and the optically measured tilt angles of the five ionic liquid
      crystals were compared to obtain their de Vries character. Four of our five
      mesogens turned out to show de Vries-like behavior with a layer shrinkage that is
      far less than that expected for conventional materials. These materials can thus
      be considered as the first de Vries-type materials among ionic liquid crystals.

PMID- 27712024
TI  - A Rapid Microwave-Assisted Thermolysis Route to Highly Crystalline Carbon
      Nitrides for Efficient Hydrogen Generation.
AB  - Highly crystalline graphitic carbon nitride (g-C3 N4 ) with decreased structural
      imperfections benefits from the suppression of electron-hole recombination, which
      enhances its hydrogen generation activity. However, producing such g-C3 N4
      materials by conventional heating in an electric furnace has proven challenging.
      Herein, we report on the synthesis of high-quality g-C3 N4 with reduced
      structural defects by judiciously combining the implementation of melamine
      cyanuric acid (MCA) supramolecular aggregates and microwave-assisted thermolysis.
      The g-C3 N4 material produced after optimizing the microwave reaction time can
      effectively generate H2 under visible-light irradiation. The highest H2 evolution
      rate achieved was 40.5 MUmol h-1 , which is two times higher than that of a g-C3
      N4 sample prepared by thermal polycondensation of the same supramolecular
      aggregates in an electric furnace. The microwave-assisted thermolysis strategy is
      simple, rapid, and robust, thereby providing a promising route for the synthesis
      of high-efficiency g-C3 N4 photocatalysts.

PMID- 27712026
TI  - De novo autoimmune hepatitis after liver transplantation: A focus on glutathione
      S-transferase theta 1.
AB  - De novo autoimmune hepatitis (DAIH) is a rare clinical condition with features
      that resemble those of autoimmune hepatitis (AIH) in patients undergoing liver
      transplantation (LT) for nonautoimmune liver disease. The diagnosis of this
      entity has been based on the presence of biochemical and histological patterns
      similar to those observed in the primary AIH, although several considerations
      must be taken into account. The impact of DAIH on graft survival is relevant, and
      early diagnosis and treatment is associated with a good longterm outcome.
      Although glutathione S-transferase theta 1 (GSTT1) alloimmune recognition has
      been shown to be involved in the pathogenesis of DAIH, further studies are
      necessary to fully determine its pathogenic mechanisms and risk factors. We
      review the pathophysiology, the most common histological patterns, the treatment
      strategies, and the longterm outcomes of DAIH after LT with a special focus on
      GSTT1. Liver Transplantation 23:75-85 2017 AASLD.

PMID- 27712025
TI  - Synthesis of Bridged Cyclopentane Derivatives by Catalytic Decarbonylative
      Cycloaddition of Cyclobutanones and Olefins.
AB  - Herein, we report an intramolecular rhodium-catalyzed decarbonylative coupling
      between cyclobutanones and alkenes that proceeds by C-C activation and provides a
      distinct approach to a diverse range of saturated bridged cyclopentane
      derivatives. In this reaction, cyclobutanones serve as cyclopropane surrogates,
      reacting in a formal (4+2-1) transformation. To demonstrate the efficacy of this
      method, it was applied in a concise synthesis of the antifungal drug Tolciclate.

PMID- 27712027
TI  - Clinical practice guidelines for the noninvasive management of low back pain: A
      systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa)
      Collaboration.
AB  - : We conducted a systematic review of guidelines on the management of low back
      pain (LBP) to assess their methodological quality and guide care. We synthesized
      guidelines on the management of LBP published from 2005 to 2014 following best
      evidence synthesis principles. We searched MEDLINE, EMBASE, CINAHL, PsycINFO,
      Cochrane, DARE, National Health Services Economic Evaluation Database, Health
      Technology Assessment Database, Index to Chiropractic Literature and grey
      literature. Independent reviewers critically appraised eligible guidelines using
      AGREE II criteria. We screened 2504 citations; 13 guidelines were eligible for
      critical appraisal, and 10 had a low risk of bias. According to high-quality
      guidelines: (1) all patients with acute or chronic LBP should receive education,
      reassurance and instruction on self-management options; (2) patients with acute
      LBP should be encouraged to return to activity and may benefit from paracetamol,
      nonsteroidal anti-inflammatory drugs (NSAIDs), or spinal manipulation; (3) the
      management of chronic LBP may include exercise, paracetamol or NSAIDs, manual
      therapy, acupuncture, and multimodal rehabilitation (combined physical and
      psychological treatment); and (4) patients with lumbar disc herniation with
      radiculopathy may benefit from spinal manipulation. Ten guidelines were of high
      methodological quality, but updating and some methodological improvements are
      needed. Overall, most guidelines target nonspecific LBP and recommend education,
      staying active/exercise, manual therapy, and paracetamol or NSAIDs as first-line
      treatments. The recommendation to use paracetamol for acute LBP is challenged by
      recent evidence and needs to be revisited. SIGNIFICANCE: Most high-quality
      guidelines recommend education, staying active/exercise, manual therapy and
      paracetamol/NSAIDs as first-line treatments for LBP. Recommendation of
      paracetamol for acute LBP is challenged by recent evidence and needs updating.

PMID- 27712028
TI  - Prediction of suicidal behavior in high risk psychiatric patients using an
      assessment of acute suicidal state: The suicide crisis inventory.
AB  - BACKGROUND: We have developed the Suicide Crisis Inventory (SCI) to evaluate the
      intensity of the Suicidal Crisis Syndrome, an acute state hypothesized to precede
      suicide attempt. The psychometric properties of the SCI, including predictive
      validity for suicidal behavior (SB), were assessed. METHODS: Adult psychiatric
      patients (n = 201) hospitalized for high suicide risk were assessed. Logistic
      regression models assessed the SCI's predictive validity for SB in the 4-8 weeks
      following hospital discharge and its incremental predictive validity over
      traditional risk factors (n = 137, 64% f/u rate). Internal structure,
      reliability, convergent and discriminant validity, and state versus trait
      properties were also assessed. RESULTS: The SCI had excellent internal
      consistency (Cronbach's alpha 0.970). The SCI total score at discharge predicted
      short-term SB with 64% sensitivity 88% specificity (OR = 13, P = .003) at its
      optimal cut score. In a test of its incremental predictive validity, SCI total
      score at discharge improved prediction of SB over traditional risk factors (Chi
      squared 5.597, P = .024, model P = .001), with AOR 2.02 (P = .030). The SCI
      admission versus discharge test-retest reliability and score distributions showed
      it to be an acute state measure. CONCLUSION: The SCI was predictive of future SB
      in high-risk psychiatric inpatients during the crucial weeks following their
      hospital discharge. Further validation in diverse patient populations is needed.

PMID- 27712029
TI  - High serum lipopolysaccharide binding protein is associated with increased
      mortality in patients with decompensated cirrhosis.
AB  - BACKGROUND & AIMS: Lipopolysaccharide-binding-protein (LBP) is an acute-phase
      protein produced by hepatocytes. Changes in LBP are associated with the dynamics
      of bacterial translocation and intestinal permeability in decompensated cirrhosis
      (DC). We assessed serum and ascitic-fluid (AF) LBP and examined their association
      with mortality in patients with DC. METHODS: Eighty-eight consecutive patients
      (73.9% males) underwent thorough diagnostic investigations for infection. LBP
      (ng/mL) was assessed in serum (N=88) and AF (n=49) by enzyme-linked-immunosorbent
      assay and expressed in natural logarithm (ln). RESULTS: Serum lnLBP was higher in
      18 patients with overt infection compared to those without (P<.001). Serum and AF
      lnLBP 13.49 and 12.11 displayed a very good-negative-predictive value of 90% and
      95.1% to rule out infection and spontaneous-bacterial-peritonitis (SBP),
      respectively. LBP was higher in serum than in AF (P<.001). Serum and AF LBP
      levels showed a positive correlation with surrogate markers of inflammation.
      Patients without overt infection were prospectively followed up. The 90-day
      mortality rate was 48% and 24.4% in patients with high (>=13.49) and low (<13.49)
      lnLBP, respectively, (log rank P=0.045). In univariate Cox regression analysis,
      neutrophils, LBP, MELD score and CRP were predictive of mortality. However, only
      high LBP (HR 8.1 95%CI 2.0-31.5, P=0.003) and MELD (HR 1.1 95%CI 1.0-1.2,
      P=0.002) were predictive of mortality in multivariate analysis. CONCLUSIONS:
      Serum and AF LBP concentrations showed a high negative-predictive-value to
      exclude infection and SBP, respectively. High serum LBP was detected in patients
      without infection at presentation who died during the 90-day-follow-up period.
      Elevated serum LBP is a marker of short-term mortality in patients without overt
      bacterial infection.

PMID- 27712030
TI  - Effectiveness of Pressure Ulcer Prevention Strategies for Adult Patients in
      Intensive Care Units: A Systematic Review.
AB  - BACKGROUND: Pressure ulcers are associated with substantial health burden, but
      could be preventable. Hospital-acquired pressure ulcers (HAPUs) prevention has
      become a priority for all healthcare settings, as it is considered a sign of
      quality of care providing. Intensive care unit (ICU) patients are at higher risk
      for HAPUs development. Despite the availability of published prevention
      strategies, there is a little evidence about which strategies can be safely
      integrated into routine standard care and have an impact on HAPUs prevention.
      AIMS: The aim was to synthesize the best available evidence regarding the
      effectiveness of single strategies designed to reduce the incidence and
      prevalence of HAPUs development in ICUs. METHODS: The search strategy was
      designed to retrieve studies published in English across CINAHL, Medline,
      Cochrane Central Register of Controlled Trials, Embase, Scopus, and Mednar
      between 2000 and 2015. All adult ICU participants were aged 18 years or over.
      This review included randomized controlled trials, quasi-experimental and
      comparative studies. The studies that were selected for retrieval were assessed
      by two independent reviewers for methodological validity prior to inclusion in
      the review using standardized critical-appraisal instruments. RESULTS: The review
      included 25 studies, and the meta-analysis revealed a statistically significant
      effect of a silicon foam dressing strategy in reducing HAPUs incidence (effect
      size = 4.62; 95% CI: 0.05-0.29; p < .00001, effect size = 4.50; 95% CI: 0.05
      0.31; p = .00001, respectively) in critically ill patients. Evidence of the
      effectiveness of nutrition, skin-care regimen, positioning and repositioning
      schedule, support surfaces, and the role of education in prevention of HAPUs
      development in the ICU was limited, which precludes strong conclusions. LINKING
      EVIDENCE TO ACTION: The review provides an evidence-based guide to future
      priorities for clinical practice. In particular, a silicone foam dressing has
      positive impact in reducing sacrum and heel HAPUs incidence in the ICU.

PMID- 27712031
TI  - Facile and Green Production of Impurity-Free Aqueous Solutions of WS2 Nanosheets
      by Direct Exfoliation in Water.
AB  - To obtain 2D materials with large quantity, low cost, and little pollution,
      liquid-phase exfoliation of their bulk form in water is a particularly
      fascinating concept. However, the current strategies for water-borne exfoliation
      exclusively employ stabilizers, such as surfactants, polymers, or inorganic
      salts, to minimize the extremely high surface energy of these nanosheets and
      stabilize them by steric repulsion. It is worth noting, however, that the
      remaining impurities inevitably bring about adverse effects to the ultimate
      performances of 2D materials. Here, a facile and green route to large-scale
      production of impurity-free aqueous solutions of WS2 nanosheets is reported by
      direct exfoliation in water. Crucial parameters such as initial concentration,
      sonication time, centrifugation speed, and centrifugation time are systematically
      evaluated to screen out an optimized condition for scaling up. Statistics based
      on morphological characterization prove that substantial fraction (66%) of the
      obtained WS2 nanosheets are one to five layers. X-ray diffraction and Raman
      characterizations reveal a high quality with few, if any, structural distortions.
      The water-borne exfoliation route opens up new opportunities for easy, clean
      processing of WS2 -based film devices that may shine in the fields of, e.g.,
      energy storage and functional nanocomposites owing to their excellent
      electrochemical, mechanical, and thermal properties.

PMID- 27712032
TI  - Insights into the Impact of Impurities and Non-Stoichiometric Effects on the
      Electrochemical Performance of Li2 MnSiO4.
AB  - A series of Li2 MnSiO4 samples with various Li, Mn, and/or Si concentrations are
      reported to study for the first time the effect of impurities and deviation from
      ideal stoichiometry on electrochemical behavior. Carbon-coated and nanosized
      powders are obtained at 600  degrees C and compared with those synthetized at 900
      degrees C. Samples are investigated using XRD, SEM, high-resolution TEM,
      attenuated total reflection infrared spectroscopy and Brunauer-Emmett-Teller
      surface area to characterize crystal structure, particle size, impurity amount,
      morphology, and surface area. Electrochemical performance depends on impurities
      such as MnO as well as crystallite size, surface area, and non-stoichiometric
      phases, which lead to the formation of additional polymorphs such as Pmnb and P21
      /n of Li2 MnSiO4 at low calcination temperatures. A systematic analysis of the
      main parameters affecting the electrochemical behavior is performed and trends in
      synthesis are identified. The findings can be applied to optimize different
      synthesis routes for attaining stoichiometric and phase-pure Pmn21 Li2 MnSiO4 as
      cathode material for Li-ion batteries.

PMID- 27712035
TI  - To B or not to B; that might just be the question. The use of lung ultrasound in
      pediatric cardiac intensive care.

PMID- 27712034
TI  - Delay of insulin initiation in patients with type 2 diabetes mellitus
      inadequately controlled with oral hypoglycemic agents (analysis of patient- and
      physician-related factors): A prospective observational DIPP-FACTOR study in
      Korea.
AB  - AIMS/INTRODUCTION: To assess the time to initiation of insulin therapy, and
      concurrently investigate both patient- and physician-related factors associated
      with delaying insulin therapy in Korean patients with type 2 diabetes
      uncontrolled by oral hypoglycemic agents (OHAs). MATERIALS AND METHODS: This
      prospective, observational disease registry study was carried out across 69
      centers in Korea. Type 2 diabetes patients who had received two or more OHAs
      within the past 5 years, had a glycated hemoglobin >=8% in the past 6 months and
      had not received insulin were included. Data recorded on data collection forms
      during a 12-month period were analyzed. RESULTS: Of 2168 patients enrolled, 1959
      were evaluated and classified as the insulin-initiated or insulin-delayed group.
      Insulin was prescribed for just 20% of the patients during a 1-year follow-up
      period, and less than half (44.5%) of the patients who were taking two OHAs
      started insulin after 6 years. Patient-related factors for delay in insulin
      initiation included older age, shorter duration of diabetes and lower glycated
      hemoglobin. Physician-related factors included age (~50 to <60 years), sex
      (women) and number (<1000) of patients consulted per month. Patient refusal
      (33.6%) and physicians' concerns of patient non-compliance (26.5%) were the major
      physician-reported reasons for delaying insulin therapy. Inconvenience of insulin
      therapy (51.6%) and fear of injection (48.2%) were the major reasons for patient
      refusal. CONCLUSIONS: Insulin initiation is delayed in patients with type 2
      diabetes uncontrolled by two or more OHAs in Korea. Patient- and physician
      related factors associated with this delay need to be addressed for better
      diabetes management.

PMID- 27712033
TI  - Reduced intensity conditioned allograft yields favorable survival for older
      adults with B-cell acute lymphoblastic leukemia.
AB  - Older adults with B-cell acute lymphoblastic leukemia (B-ALL) have poor survival.
      We examined the effectiveness of reduced intensity conditioning (RIC)
      hematopoietic cell transplant (HCT) in adults with B-ALL age 55 years and older
      and explored prognostic factors associated with long-term outcomes. Using CIBMTR
      registry data, we evaluated 273 patients (median age 61, range 55-72) with B-ALL
      with disease status in CR1 (71%), >CR2 (17%) and Primary Induction Failure
      (PIF)/Relapse (11%), who underwent RIC HCT between 2001 and 2012 using mostly
      unrelated donor (59%) or HLA-matched sibling (32%). Among patients with available
      cytogenetic data, the Philadelphia chromosome (Ph+) was present in 50%. The 3
      year cumulative incidences of nonrelapse mortality (NRM) and relapse were 25%
      (95% confidence intervals (CI): 20-31%) and 47% (95% CI: 41-53%), respectively.
      Three-year overall survival (OS) was 38% (95% CI: 33-44%). Relapse remained the
      leading cause of death accounting for 49% of all deaths. In univariate analysis,
      3 year risk of NRM was significantly higher with reduced Karnofsky performance
      status (KPS <90: 34% (95% CI: 25-43%) versus KPS >=90 (18%; 95% CI: 12-24%, P =
      0.006). Mortality was increased in older adults (66+ vs. 55-60: Relative Risk
      [RR] 1.51 95% CI: 1.00-2.29, P = 0.05) and those with advanced disease (RR 2.13;
      95% CI: 1.36-3.34, P = 0.001). Survival of patients in CR1 yields 45% (95% CI: 38
      52%) at 3 years and no relapse occurred after 2 years. We report promising OS and
      acceptable NRM using RIC HCT in older patients with B-ALL. Disease status in CR1
      and good performance status are associated with improved outcomes. Am. J.
      Hematol. 92:42-49, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27712036
TI  - In vitro evaluation of poly (lactic-co-glycolic acid)/polyisoprene fibers for
      soft tissue engineering.
AB  - The polymeric blend of poly (lactic-co-glycolic acid) (PLGA) and polyisoprene
      (PI) has recently been explored for application as stents for tracheal stenosis
      and spring for the treatment of craniosynostosis. From the positive results
      presented in other biomedical applications comes the possibility of investigating
      the application of this material as scaffold for tissue engineering (TE),
      acquiring a deeper knowledge about the polymeric blend by exploring a new
      processing technique while attending to the most fundamental demands of TE
      scaffolds. PLGA/PI was processed into randomly oriented microfibers through the
      dripping technique and submitted to physical-chemical and in vitro
      characterization. The production process of fibers did not show an effect over
      the polymer's chemical composition, despite the fact that PLGA and PI were
      observed to be immiscible. Mechanical assays reinforce the suitability of these
      scaffolds for soft tissue applications. Skeletal muscle cells demonstrated
      increases in metabolic activity and proliferation to the same levels of the
      control group. Human dermal fibroblasts didn't show the same behaviour, but
      presented cell growth with the same development profile as presented in the
      control group. It is plausible to believe that PLGA/PI fibrous three-dimensional
      scaffolds are suitable for applications in soft tissue engineering. (c) 2016
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2581
      2591, 2017.

PMID- 27712038
TI  - Evaluation of an oral direct factor Xa inhibitor anticoagulant in healthy adult
      horses.
AB  - OBJECTIVE: To assess whether an oral direct factor Xa inhibitor (DiXaI)
      anticoagulant drug used at the low end of the recommended dose in people achieves
      presumed prophylactic plasma concentrations and does not induce bleeding in
      horses. DESIGN: Experimental study. SETTING: Field study. ANIMALS: Ten healthy
      adult horses. INTERVENTIONS: A DiXaI was administered at a dose of 0.125 mg/kg
      every 24 h orally for 4 days. Following a wash-out period of 2 weeks, 8 of 10
      horses received daily subcutaneous doses of a low molecular weight heparin
      (dalteparin) for 4 consecutive days at 50 IU/kg. In both trials, antifactor Xa
      activity was measured at baseline time and 3 hours after each dose
      administration. Activated partial thromboplastin time, prothrombin time,
      hematocrit, erythrocyte agglutination, and platelet aggregation were monitored
      throughout the study. In addition, an in vitro spiking experiment was performed
      to demonstrate anticoagulant activity of this DiXaI in horse plasma. MAIN
      RESULTS: When treated with the DiXaI, this group of horses did not achieve the
      suggested thromboprophylactic plasma range of antifactor Xa activity (0.1-0.2
      IU/mL), except for 1 horse after the first administration of the drug. In
      contrast, median values of plasma antifactor Xa activity 3 hours after receiving
      dalteparin were within the prophylactic range (0.16 IU/mL). No hemorrhagic events
      or erythrocyte agglutination were observed. In vitro addition of this DiXaI
      caused a concentration-dependent effect in antifactor Xa activity. CONCLUSIONS:
      At the low end of the recommended dose in people this oral formulation of DiXaI
      did not reach prophylactic plasma antifactor Xa activity in this group of healthy
      adult horses. Further studies are warranted in order to establish the
      prophylactic dose for horses.

PMID- 27712037
TI  - In vivo cytochrome P450 activity alterations in diabetic nonalcoholic
      steatohepatitis mice.
AB  - Nonalcoholic steatohepatitis (NASH) has been identified as a source of
      significant interindividual variation in drug metabolism. A previous ex vivo
      study demonstrated significant changes in hepatic Cytochrome P450 (CYP) activity
      in human NASH. This study evaluated the in vivo activities of multiple CYP
      isoforms simultaneously in prominent diabetic NASH mouse models. The
      pharmacokinetics of CYP selective substrates: caffeine, losartan, and omeprazole
      changed significantly in a diabetic NASH mouse model, indicating attenuation of
      the activity of Cyp1a2 and Cyp2c29, respectively. Decreased mRNA expression of
      Cyp1a2 and Cyp2c29, as well as an overall decrease in CYP protein expression, was
      found in the diabetic NASH mice. Overall, these data suggest that the diabetic
      NASH model only partially recapitulates the human ex vivo CYP alteration pattern.
      Therefore, in vivo determination of the effects of NASH on CYP activity should be
      conducted in human, and more appropriate models are required for future drug
      metabolism studies in NASH.

PMID- 27712039
TI  - Efficacy of topical flutamide in the treatment of melasma.

PMID- 27712040
TI  - Donor safety in living donor liver donation: An Italian multicenter survey.
AB  - Major concerns about donor morbidity and mortality still limit the use of living
      donor liver transplantation (LDLT) to overcome the organ shortage. The present
      study assessed donor safety in LDLT in Italy reporting donor postoperative
      outcomes in 246 living donation procedures performed by 7 transplant centers.
      Outcomes were evaluated over 2 time periods using the validated Clavien 5-tier
      grading system, and several clinical variables were analyzed to determine the
      risk factors for donor morbidity. Different grafts were obtained from the 246
      donor procedures (220 right lobe, 10 left lobe, and 16 left lateral segments).
      The median follow-up after donation was 112 months. There was no donor mortality.
      One or more complications occurred in 82 (33.3%) donors, and 3 of them had
      intraoperative complications (1.2%). Regardless of graft type, the rate of major
      complications (grade >= 3) was 12.6% (31/246). The overall donor morbidity and
      the rate of major complications did not differ significantly over time: 26
      (10.6%) donors required hospital readmission throughout the follow-up period,
      whereas 5 (2.0%) donors required reoperation. Prolonged operative time (>400
      minutes), intraoperative hypotension (systolic < 100 mm Hg), vascular
      abnormalities, and intraoperative blood loss (>300 mL) were multivariate risk
      factors for postoperative donor complications. In conclusion, from the standpoint
      of living donor surgery, a meticulous and well-standardized technique that
      reduces operative time and prevents blood loss and intraoperative hypotension may
      reduce the incidence of donor complications. Transparency in reporting results
      after LDLT is mandatory, and we should continue to strive for zero donor
      mortality. Liver Transplantation 23 184-193 2017 AASLD.

PMID- 27712042
TI  - Erratum: Predicting Melting Points of Organic Molecules: Applications to Aqueous
      Solubility Prediction Using the General Solubility Equation.

PMID- 27712041
TI  - Functional anatomy of the mammalian sperm flagellum.
AB  - The eukaryotic flagellum is the organelle responsible for the propulsion of the
      male gamete in most animals. Without exception, sperm of all mammalian species
      use a flagellum for swimming. The mammalian sperm has a centrally located 9 + 2
      arrangement of microtubule doublets and hundreds of accessory proteins that
      together constitute an axoneme. However, they also possess several characteristic
      peri-axonemal structures that make the mammalian sperm tail function differently.
      These modifications include nine outer dense fibers (ODFs) that are paired with
      the nine outer microtubule doublets of the axoneme, and are anchored in a
      structure called the connecting piece located at the base. The presence of the
      ODFs and connecting piece, and the absence of a basal body, dictate that physical
      forces generated by the dynein motors are transmitted to the base of the
      flagellum through the ODFs. Mammalian sperm flagella also possess a mitochondrial
      and a fibrous sheath that encircle most of the axoneme. These sheaths and the
      ODFs add mechanical rigidity to the flagellum creating the functional effect of
      increasing bend wavelength, which requires the entrainment of more dynein motors
      in the production of a single wave. The sheaths also act as a retinaculum and
      maintain the integrity of the central axoneme when large bending torques are
      generated by dynein. Large torque production is crucial to the process of
      hyperactivation and the unique motility transitions associated with effective
      fertilizing capacity. Consequently, these specialized anatomical features are
      essential for the effective interaction of sperm with the female reproductive
      tract and ovum. (c) 2016 Wiley Periodicals, Inc.

PMID- 27712043
TI  - Molecular Simulations Bring New Insights into Protoporphyrinogen IX
      Oxidase/Protoporphyrinogen IX Interaction Modes.
AB  - Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) catalyzes the oxidation of
      protoporphyrinogen IX (protogen IX) to protoporphyrin IX (proto IX) in the
      haem/chlorophyll biosynthetic pathway. Although extensive studies of PPO have
      already afforded many insights into its biological function and its significance
      to agriculture and medicine, details of the enzymatic mechanism as well as the
      nature of the specific amino acids involved in substrate binding still remain
      largely unknown due to the lack of structural information about protogen IX
      binding to PPO. In this study, we carried out a detailed and systematic
      investigation on the binding mode of protogen IX in the Nicotiana tabacum PPO
      (mtPPO) by performing a computational docking followed by molecular simulations,
      quantum mechanics calculations, and an integrated analysis. The proposed binding
      mode was consistent with experimental studies, and several potential key residues
      that have not been investigated in previous studies, such as Thr70, Arg233,
      Ser235, Ser474 and Lys477, were identified. In addition, we compared the binding
      modes of protogen IX in mtPPO and Homo sapiens PPO, and found their differences.
      Considering the low sequence identity and the differences of biochemical
      properties among the PPOs from various species, the investigation could provide a
      valuable basis for the design of PPO inhibitors with high potency and species
      selectivity.

PMID- 27712044
TI  - Molecular Polarization Potential as a Molecular Descriptor to Predict Biological
      Activity of Dioxins and Dibenzofurans.
AB  - Molecular interaction potential (MIP) maps are a powerful tool to develop
      structure-activity relationships of a series of compounds. In the present study
      we have studied the effect of molecular polarization on the description of the
      toxicity of a series of dioxins and benzofurans using their MIPs. Specifically,
      we have used principal component analysis in an exploratory way to understand the
      common structural features that describe the toxicity of these molecules through
      the analysis of their MIPs and each of their components, i.e.; molecular
      electrostatic and polarization potentials. Moreover, we have developed a
      predictive model using PLS that permits to evaluate the toxicity of compounds
      belonging to any of the families of compounds studied in the present work on the
      basis of their molecular electrostatic and interaction potentials.

PMID- 27712046
TI  - Physicochemical Properties, Fatty Acid Profiles, and Sensory Characteristics of
      Fermented Beef Sausage by Probiotics Lactobacillus plantarum IIA-2C12 or
      Lactobacillus acidophilus IIA-2B4.
AB  - Probiotics may be used to enhance the functionality and nutritional values of
      fermented sausages. This study aims to evaluate the physicochemical and sensory
      properties of beef sausages fermented by lactic acid bacteria of Lactobacillus
      plantarum IIA-2C12 and L. acidophilus IIA-2B4. These strains were isolated from
      beef cattle and have shown to display probiotic features. While the nutrient
      contents were not affected by the probiotics, the pH, texture, and color varied
      among the sausages. Further analysis on fatty acids showed different profiles of
      saturated (C14:0, C17:0, and C20:0) and unsaturated (C14:1, C18:1n9c, C18:2n6c,
      and C22:6n3) fatty acids in sausages with probiotics. Gas chromatography-mass
      spectrometry further revealed some flavor development compounds including acid,
      alcohols, aldehydes, aromatic, ketones, sulfur, hydrocarbons and terpenes, varied
      among the sausages. Hedonic test showed no difference in the preference toward
      aroma, texture, and color for untrained panelists.

PMID- 27712045
TI  - Systematic Analysis of Tyrosine Kinase Inhibitor Response to RET Gatekeeper
      Mutations in Thyroid Cancer.
AB  - The proto-oncogene protein RET is a receptor tyrosine kinase that plays an
      important role in the development and progress of various human cancers.
      Currently, targeting RET with small-molecule tyrosine kinase inhibitors (TKIs)
      has been established as promising therapeutic strategy for thyroid carcinoma
      (TC). However, two gatekeeper mutations V804M and V804L in RET kinase domain have
      been frequently observed to cause drug resistance during the targeted therapy,
      largely limiting the application of reversible TKIs in TC. Here, we described an
      integrative protocol that combined literature curation, computational analysis,
      and in vitro kinase assay to systematically investigate the response profile of 9
      approved RET TKIs to the two clinical RET gatekeeper mutations. It was revealed
      that the two mutations exhibit a similar energetic behavior to influence TKI
      binding, which can moderately decrease competitive inhibitor affinity and
      modestly increase substrate ATP affinity simultaneously. However, the binding
      potency of few second-generation kinase inhibitors such as Ponatinib and
      Alectinib can be improved to overcome the increased ATP affinity, thus restoring
      their inhibitory activity against the kinase mutants. Subsequently, the
      established protocol was employed to investigate the response profile of 4
      commercially available RET TKIs that are under preclinical or clinical
      development. Three out of the four TKIs were found to become resistant upon the
      mutations due to steric hindrance effect introduced by the mutated residues,
      while the remaining one was moderately sensitized by the mutations since the
      mutated residues can form additional hydrophobic and van der Waals interactions
      with the inhibitor.

PMID- 27712048
TI  - Multidimensional Mass Spectrometry of Synthetic Polymers and Advanced Materials.
AB  - Multidimensional mass spectrometry interfaces a suitable ionization technique and
      mass analysis (MS) with fragmentation by tandem mass spectrometry (MS2 ) and an
      orthogonal online separation method. Separation choices include liquid
      chromatography (LC) and ion-mobility spectrometry (IMS), in which separation
      takes place pre-ionization in the solution state or post-ionization in the gas
      phase, respectively. The MS step provides elemental composition information,
      while MS2 exploits differences in the bond stabilities of a polymer, yielding
      connectivity and sequence information. LC conditions can be tuned to separate by
      polarity, end-group functionality, or hydrodynamic volume, whereas IMS adds
      selectivity by macromolecular shape and architecture. This Minireview discusses
      how selected combinations of the MS, MS2 , LC, and IMS dimensions can be applied,
      together with the appropriate ionization method, to determine the constituents,
      structures, end groups, sequences, and architectures of a wide variety of homo-
      and copolymeric materials, including multicomponent blends, supramolecular
      assemblies, novel hybrid materials, and large cross-linked or nonionizable
      polymers.

PMID- 27712047
TI  - Coupling between spontaneous pupillary fluctuations and brain activity relates to
      inattentiveness.
AB  - Autonomic activity in neurological and psychiatric disorders is often
      dysregulated, particularly in the context of attentional behaviors. This suggests
      that interplay between the autonomic nervous system and aspects of the central
      nervous system subserving attention may be disrupted in these conditions. Better
      understanding these interactions and their relationship with individual variation
      in attentional behaviors could facilitate development of mechanistic biomarkers.
      We identified brain regions defined by trait-sensitive central-autonomic coupling
      as a first step in this process. As spontaneous neural activity measured during
      the resting state is sensitive to phenotypic variability, unconfounded by task
      performance, we examined whether spontaneous fluctuations in brain activity and
      an autonomic measure, pupil diameter, were coupled during the resting state, and
      whether that coupling predicted individual differences in attentional behavior.
      By employing concurrent pupillometry and fMRI during the resting state, we
      observed positive coupling in regions comprising cingulo-opercular, default mode,
      and fronto-parietal networks, as well as negative coupling with visual and
      sensorimotor regions. Individuals less prone to distractibility in everyday
      behavior demonstrated stronger positive coupling in cingulo-opercular regions
      often associated with sympathetic activity. Overall, our results suggest that
      individuals less prone to distractibility have tighter intrinsic coordination
      between specific brain areas and autonomic systems, which may enable adaptive
      autonomic shifts in response to salient environmental cues. These results suggest
      that incorporating autonomic indices in resting-state studies should be useful in
      the search for biomarkers for neurological and psychiatric disorders.

PMID- 27712049
TI  - Thirteen years of invasive and noninvasive home ventilation for children in a
      developing country: A retrospective study.
AB  - INTRODUCTION: Home ventilation (HV) for children is growing rapidly worldwide.
      The aim was to describe (1) the sociodemographic characteristics of children on
      HV and (2) the indications for, means and outcome of initiating HV in children
      from a developing country. METHODOLOGY: This retrospective study included
      patients sent home on noninvasive or invasive ventilation, over 13 years, by the
      pediatric respiratory unit in a single center. Children who declined treatment
      were excluded. RESULTS: Seventy children were initiated on HV: 85.7% on
      noninvasive ventilation, 14.3% on invasive ventilation. There was about a
      threefold increase from 2001-2008 (n = 18) to 2009-2014 (n = 52). Median (range)
      age of initiating HV was 11 (1-169) months and 73% of children were <2 years old.
      Common indications for HV were respiratory (57.2%), chest/spine anomalies
      (11.4%), and neuromuscular (10.0%). Fifty-two percent came off their devices with
      a median (interquartile range) usage duration of 12 (4.8, 21.6) months. Ten
      children (14.3%) died with one avoidable death. Children with neuromuscular
      disease were less likely to come off their ventilator (0.0%) compared to children
      with respiratory disease (62.1%). Forty-one percent of parents bought their
      equipment, whereas 58.6% borrowed their equipment from the medical social work
      department and other sources. CONCLUSION: HV in a resource-limited country is
      possible. Children with respiratory disease made up a significant proportion of
      those requiring HV and were more likely to be weaned off. The mortality rate was
      low. The social work department played an important role in facilitating early
      discharge. Pediatr Pulmonol. 2017;52:500-507. (c) 2016 Wiley Periodicals, Inc.

PMID- 27712051
TI  - Role of Hydrogen and Oxygen Activation over Pt and Pd-Doped Composites for
      Catalytic Hydrogen Combustion.
AB  - Removal of excess amount of hydrogen in a catalytic route is a safety measure to
      be implemented in fuel cell technologies and in nuclear power plants. Hydrogen
      and oxygen activation are crucial steps for hydrogen combustion that can be
      achieved by modifying supports with suitable noble metals. In the present study,
      Pt- and Pd-substituted Co3O4-ZrO2 (CZ) were synthesized using PEG-assisted
      sonochemical synthesis. Ionic states of Pt and Pd in CZ supports were analyzed by
      X-ray photoelectron spectroscopy. Pd and Pt improved H2 and O2 activation
      extensively, which reduced the temperature of 50% conversion (T50%) to 33 
      degrees C compared with the support (CZ). The activation energy of PdCZ catalyst
      was decreased by more than 2 folds (13.4 +/- 1.2 kJ mol-1) compared with CZ (34.3
      +/- 2.3 kJ mol-1). The effect of oxygen vacancies in the reaction mechanism is
      found to be insignificant with Pt- and Pd-substituted CZ supports. However,
      oxygen vacancies play an important role when CZ alone was used as catalyst. The
      importance of hydrogen and oxygen activation as well as the oxygen vacancies in
      mechanism was studied by H2-TPD, H2-TPR, and in situ FTIR spectroscopy.

PMID- 27712050
TI  - Human Dopamine Receptor-Conjugated Multidimensional Conducting Polymer Nanofiber
      Membrane for Dopamine Detection.
AB  - In the brain and central nervous system, dopamine plays a crucial role as a
      neurotransmitter or a local chemical messenger for interneuronal communication.
      Dopamine is associated with renal, hormonal, and cardiovascular systems.
      Additionally, dopamine dysfunction is known to cause serious illnesses, such as
      Parkinson's disease and Alzheimer's disease. Therefore, dopamine detection is
      essential for medical diagnosis and disease prevention and requires a novel
      strategy with high sensitivity and selectivity and a rapid response. Herein, we
      present a novel human dopamine receptor (hDRD1)-conjugated multidimensional
      conducting polymer nanofiber (NF) membrane for the selective and sensitive
      detection of dopamine. The membrane, which consists of multidimensional
      carboxylated poly(3,4-ethylenedioxythiophene) (MCPEDOT) NFs with nanorods, is
      used as a transistor in a liquid-ion gated field-effect transistor (FET)-based
      biosensor. Interestingly, hDRD1 is first expressed in Escherichia coli before it
      is immobilized onto the MCPEDOT NF. The hDRD1-MCPEDOT NF-based FET exhibits a
      rapid real-time response (<2 s) with high dopamine selectivity and sensitivity
      performance (approximately 100 fM). Furthermore, this FET device can be
      integrated into a poly(dimethylsiloxane)-based microfluidic system and also can
      retain its high performance in the integrated system, which results in the
      generation of large-scale dopamine biosensors with a novel geometry.

PMID- 27712052
TI  - Antibacterial Adhesion of Poly(methyl methacrylate) Modified by Borneol Acrylate.
AB  - Poly(methyl methacrylate) (PMMA) is a widely used biomaterial. But there is still
      a challenge facing its unwanted bacterial adhesion because the subsequent biofilm
      formation usually leads to failure of related implants. Herein, we present a
      borneol-modified PMMA based on a facile and effective stereochemical strategy,
      generating antibacterial copolymer named as P(MMA-co-BA). It was synthesized by
      free radical polymerization and studied with different ratio between methyl
      methacrylate (MMA) and borneol acrylate (BA) monomers. NMR, GPC, and EA, etc.,
      were used to confirm their chemical features. Their films were challenged with
      Escherichia coli (Gram-negative) and Bacillus subtilis (Gram-positive), showing a
      BA content dependent antibacterial performance. The minimum effective dose should
      be 10%. Then in vivo subcutaneous implantations in mice demonstrated their
      biocompatibilities through routine histotomy and HE staining. Therefore, P(MMA-co
      BA)s not only exhibited their unique antibacterial character but also suggested a
      potential for the safe usage of borneol-modified PMMA frame and devices for
      further implantation.

PMID- 27712053
TI  - Simultaneous and Sensitive Detection of Multisite 5-Methylcytosine Including Non
      CpG Sites at Single-5mC-Resolution.
AB  - The methylation status of multiplexed methylcytosine sites can be simultaneously
      monitored by ligation-depended PCR assay. The ability of quantitative detection
      of multiplexed sites in one PCR reaction makes it a good choice for detecting
      methylation at both CpG and non-CpG sites for research and diagnosis of disease
      compared with others. The assay can determine as low as 20 aM methylated DNA and
      has been successfully applied to the genomic DNA sample derived from cancer cell
      lines.

PMID- 27712054
TI  - Bioethanol Blending Reduces Nanoparticle, PAH, and Alkyl- and Nitro-PAH Emissions
      and the Genotoxic Potential of Exhaust from a Gasoline Direct Injection Flex-Fuel
      Vehicle.
AB  - Bioethanol as an alternative fuel is widely used as a substitute for gasoline and
      also in gasoline direct injection (GDI) vehicles, which are quickly replacing
      traditional port-fuel injection (PFI) vehicles. Better fuel efficiency and
      increased engine power are reported advantages of GDI vehicles. However,
      increased emissions of soot-like nanoparticles are also associated with GDI
      technology with yet unknown health impacts. In this study, we compare emissions
      of a flex-fuel Euro-5 GDI vehicle operated with gasoline (E0) and two
      ethanol/gasoline blends (E10 and E85) under transient and steady driving
      conditions and report effects on particle, polycyclic aromatic hydrocarbon (PAH),
      and alkyl- and nitro-PAH emissions and assess their genotoxic potential. Particle
      number emissions when operating the vehicle in the hWLTC (hot started worldwide
      harmonized light-duty vehicle test cycle) with E10 and E85 were lowered by 97 and
      96% compared with that of E0. CO emissions dropped by 81 and 87%, while CO2
      emissions were reduced by 13 and 17%. Emissions of selected PAHs were lowered by
      67-96% with E10 and by 82-96% with E85, and the genotoxic potentials dropped by
      72 and 83%, respectively. Ethanol blending appears to reduce genotoxic emissions
      on this specific flex-fuel GDI vehicle; however, other GDI vehicle types should
      be analyzed.

PMID- 27712056
TI  - Size-Dependent Fullerene-Fullerene Interactions in Water: A Molecular Dynamics
      Study.
AB  - Nested fullerenes display a range of unique properties influenced by their size
      and shape. In this paper, the size- and shape-dependent aggregation of nested
      fullerenes in water is studied using explicit solvent molecular dynamic
      simulations. It is shown that water forms a layered structure near the surface of
      the particle, with the density of interfacial water increasing with increasing
      particle size. Meanwhile, water molecules near the extended facets of large
      nested fullerenes are unable to maintain their hydrogen bonding network, leading
      to a shape and size mediated structuring of surrounding waters. These distortions
      affect the overall association kinetics of particles in water with spherically
      shaped particles transitioning quickly into contact, while larger fullerenes,
      characterized by a lower sphericity, cluster at a much slower rate.

PMID- 27712055
TI  - Discovery and Characterization of Allosteric WNK Kinase Inhibitors.
AB  - Protein kinases are known for their highly conserved adenosine triphosphate (ATP)
      binding site, rendering the discovery of selective inhibitors a major challenge.
      In theory, allosteric inhibitors can achieve high selectivity by targeting less
      conserved regions of the kinases, often with an added benefit of retaining
      efficacy under high physiological ATP concentration. Although often overlooked in
      favor of ATP-site directed approaches, performing a screen at high ATP
      concentration or stringent hit triaging with high ATP concentration offers
      conceptually simple methods of identifying inhibitors that bind outside the ATP
      pocket. Here, we applied the latter approach to the With-No-Lysine (K) (WNK)
      kinases to discover lead molecules for a next-generation antihypertensive that
      requires a stringent safety profile. This strategy yielded several ATP
      noncompetitive WNK1-4 kinase inhibitors, the optimization of which enabled
      cocrystallization with WNK1, revealing an allosteric binding mode consistent with
      the observed exquisite specificity for WNK1-4 kinases. The optimized compound
      inhibited rubidium uptake by sodium chloride cotransporter 1 (NKCC1) in HT29
      cells, consistent with the reported physiology of WNK kinases in renal
      electrolyte handling.

PMID- 27712058
TI  - Inhibition and Promotion of Heat-Induced Gelation of Whey Proteins in the
      Presence of Calcium by Addition of Sodium Caseinate.
AB  - Heat-induced aggregation and gelation of aqueous solutions of whey protein
      isolate (WPI) in the presence of sodium caseinate (SC) and CaCl2 was studied at
      pH 6.6. The effect of adding SC (0-100 g/L) on the structure of the aggregates
      and the gels was investigated by light scattering and confocal laser scanning
      microscopy at different CaCl2 concentration ([CaCl2] = 0-30 mM). The gelation
      process was studied by oscillatory shear rheology. At the whey protein
      concentrations studied here (34 and 60 g/L), no gels were formed in the absence
      of CaCl2 and SC. However, WPI solutions gelled above a critical CaCl2
      concentration that increased with increasing SC concentration. In the absence of
      CaCl2, WPI gels were formed only above a critical SC concentration. The critical
      SC concentration needed to induce WPI gelation decreased weakly when CaCl2 was
      added. In an intermediate range of CaCl2 concentrations, gels were formed both at
      low and high SC concentrations, but not at intermediate SC concentrations.
      Finally, at high CaCl2 concentrations gels were formed at all SC concentrations.
      The gelation rate and the gel structure of the gels formed at low and high casein
      concentrations were very different. The effect of SC on the thermal gelation of
      WPI was interpreted by competition for Ca2+, a chaperon effect, and microphase
      separation.

PMID- 27712059
TI  - Nano Day: Celebrating the Next Decade of Nanoscience and Nanotechnology.
AB  - Nanoscience and nanotechnology are poised to contribute to a wide range of
      fields, from health and medicine to electronics, energy, security, and more.
      These contributions come both directly in the form of new materials, interfaces,
      tools, and even properties as well as indirectly by connecting fields together.
      We celebrate how far we have come, and here, we look at what is to come over the
      next decade that will leverage the strong and growing base that we have built in
      nanoscience and nanotechnology.

PMID- 27712057
TI  - Selective Uptake of Alkaline Earth Metals by Cyanobacteria Forming Intracellular
      Carbonates.
AB  - The uptakes of calcium (Ca), strontium (Sr), and barium (Ba) by two
      cyanobacterial strains, Cyanothece sp. PCC7425 and Gloeomargarita lithophora,
      both forming intracellular carbonates, were investigated in laboratory cultures.
      In the culture medium BG-11 amended with 250 MUM Ca and 50 or 250 MUM Sr and Ba,
      G. lithophora accumulated first Ba, then Sr, and finally Ca. Sr and Ba were
      completely accumulated by G. lithophora cells at rates between 0.02 and 0.10 fmol
      h-1 cell-1 and down to extracellular concentrations below the detection limits of
      inductively coupled plasma atomic emission spectroscopy. Accumulation of Sr and
      Ba did not affect the growth rate of the strain. This sequential accumulation
      occurred mostly intracellularly within polyphosphate and carbonate granules and
      resulted in the formation of core-shell structures in carbonates. In contrast,
      Cyanothece sp. PCC7425 showed neither a preferential accumulation of heavier
      alkaline earth metals nor core-shell structures in the carbonates. This indicated
      that fractionation between alkaline earth metals was not inherent to
      intracellularly calcifying cyanobacteria but was likely a genetically based trait
      of G. lithophora. Overall, the capability of G. lithophora to sequester
      preferentially Sr and Ba at high rates may be of considerable interest for
      designing new remediation strategies and better understanding the geochemical
      cycles of these elements.

PMID- 27712060
TI  - Composition by LC-MS/MS of New Carotenoid Esters in Mango and Citrus.
AB  - Interest in the composition of carotenoid esters of fruits is growing because
      esterification may affect their bioavailability. Thus, the aim was to provide a
      detailed identification of carotenoid esters in citrus and mango. Orange cv.
      'Valencia' and cv. 'Pera' presented 9 free carotenoids, 38 monoesters, and 60
      diesters. Violaxanthin and luteoxanthin derivatives were the major ones, followed
      by antheraxanthin, lutein, zeaxanthin, beta-cryptoxanthin, and zeinoxanthin
      esters, many of them reported for the first time in orange pulp. The carotenoid
      ester composition of tangor cv. 'Murcott', reported for the first time, showed 8
      free carotenoids, 34 monoesters, and 33 diesters, with beta-cryptoxanthin esters
      as major compounds, followed by violaxanthin and zeaxanthin esters. In citrus,
      carotenoids were acylated mainly with capric, lauric, myristic, myristoleic,
      palmitic, palmitoleic, and oleic acids. In mango, 5 free carotenoids, 2
      monoesters, and 19 diesters were identified, from which many violaxanthin and
      neoxanthin esters were reported for the first time.

PMID- 27712061
TI  - Simultaneous Microcystis Algicidal and Microcystin Degrading Capability by a
      Single Acinetobacter Bacterial Strain.
AB  - Measures for removal of toxic harmful algal blooms often cause lysis of algal
      cells and release of microcystins (MCs). In this study, Acinetobacter sp. CMDB-2
      that exhibits distinct algal lysing activity and MCs degradation capability was
      isolated. The physiological response and morphological characteristics of toxin
      producing Microcystis aeruginosa, the dynamics of intra- and extracellular MC-LR
      concentration were studied in an algal/bacterial cocultured system. The results
      demonstrated that Acinetobacter sp. CMDB-2 caused thorough decomposition of algal
      cells and impairment of photosynthesis within 24 h. Enhanced algal lysis and MC
      LR release appeared with increasing bacterial density from 1 * 103 to 1 * 107
      cells/mL; however, the MC-LR was reduced by nearly 94% within 14 h irrespective
      of bacterial density. Measurement of extracellular and intracellular MC-LR
      revealed that the toxin was decreased by 92% in bacterial cell incubated systems
      relative to control and bacterial cell-free filtrate systems. The results
      confirmed that the bacterial metabolite caused 92% lysis of Microcystis
      aeruginosa cells, whereas the bacterial cells were responsible for approximately
      91% reduction of MC-LR. The joint efforts of the bacterium and its metabolite
      accomplished the sustainable removal of algae and MC-LR. This is the first report
      of a single bacterial strain that achieves these dual actions.

PMID- 27712062
TI  - Dual Detection System for Simultaneous Measurement of Intracellular Fluorescent
      Markers and Cellular Secretion.
AB  - Glucose-stimulated insulin secretion from pancreatic beta-cells within islets of
      Langerhans plays a critical role in maintaining glucose homeostasis. Although
      this process is essential for maintaining euglycemia, the underlying
      intracellular mechanisms that control it are still unclear. To allow simultaneous
      correlation between intracellular signal transduction events and extracellular
      secretion, an analytical system was developed that integrates fluorescence
      imaging of intracellular probes with high-speed automated insulin immunoassays.
      As a demonstration of the system, intracellular [Ca2+] ([Ca2+]i) was measured by
      imaging Fura-2 fluorescence simultaneously with insulin secretion from islets
      exposed to elevated glucose levels. Both [Ca2+]i and insulin were oscillatory
      during application of 10 mM glucose with temporal and quantitative profiles
      similar to what has been observed elsewhere. In previous work, sinusoidal glucose
      levels have been used to test the entrainment of islets while monitoring either
      [Ca2+]i or insulin levels; using this newly developed system, we show
      unambiguously that oscillations of both [Ca2+]i and insulin release are entrained
      to oscillatory glucose levels and that the temporal correlation of these are
      maintained throughout the experiment. It is expected that the developed
      analytical system can be expanded to investigate a number of other intracellular
      messengers in islets or other stimulus-secretion pathways in different cells.

PMID- 27712065
TI  - Quantum Dynamics of the 17O + 32O2 Collision Process.
AB  - We report full quantum integral and differential cross sections and rate
      constants for the 17O + 32O2 collision, possibly reactive, process. This
      constitutes the first quantum scattering study of the 17O16O16O system. We
      emphasize the comparison with the 18O + 32O2 collision in close connection to the
      mass independent fractionation (thereafter refered to as MIF) puzzle for ozone in
      atmospheric chemistry. We find similar general trends in the cross sections and
      rate constants for both rare isotopes, but we note some singular behaviors
      peculiar to the use of 17O isotope, particularly at the lowest collision
      energies.

PMID- 27712064
TI  - Shape-Controlled Synthesis of All-Inorganic CsPbBr3 Perovskite Nanocrystals with
      Bright Blue Emission.
AB  - We developed a colloidal synthesis of CsPbBr3 perovskite nanocrystals (NCs) at a
      relative low temperature (90  degrees C) for the bright blue emission which
      differs from the original green emission (~510 nm) of CsPbBr3 nanocubes as
      reported previously. Shapes of the obtained CsPbBr3 NCs can be systematically
      engineered into single and lamellar-structured 0D quantum dots, as well as face
      to-face stacking 2D nanoplatelets and flat-lying 2D nanosheets via tuning the
      amounts of oleic acid (OA) and oleylamine (OM). They exhibit sharp excitonic PL
      emissions at 453, 472, 449, and 452 nm, respectively. The large blue shift
      relative to the emission of CsPbBr3 bulk crystal can be ascribed to the strong
      quantum confinement effects of these various nanoshapes. PL decay lifetimes are
      measured, ranging from several to tens of nanoseconds, which infers the higher
      ratio of exciton radiative recombination to the nonradiative trappers in the
      obtained CsPbBr3 NCs. These shape-controlled CsPbBr3 perovskite NCs with the
      bright blue emission will be widely used in optoelectronic applications,
      especially in blue LEDs which still lag behind compared to the better developed
      red and green LEDs.

PMID- 27712063
TI  - Ligand-Promoted Meta-C-H Amination and Alkynylation.
AB  - Meta-C-H amination and meta-C-H alkynylation using a modified norbornene (methyl
      bicyclo[2.2.1]hept-2-ene-2-carboxylate) as a transient mediator has been
      developed for the first time. Both the identification of a mono-protected 3-amino
      2-hydroxypyridine/pyridone type ligand and the use of methyl bicyclo[2.2.1]hept-2
      ene-2-carboxylate as the mediator are crucial for realizing these two
      unprecedented meta-C-H transformations. A variety of substrates are compatible
      with both meta-C-H amination and meta-C-H alkynylation. Amination and
      alkynylation of heterocyclic substrates including indole, indoline, and indazole
      afford the desired products in moderate to high yields.

PMID- 27712066
TI  - Characterization of Key Odorants Causing a Fusty/Musty Off-Flavor in Native Cold
      Pressed Rapeseed Oil by Means of the Sensomics Approach.
AB  - The sensomics approach was used to clarify the formation of the fusty/musty off
      flavor of native cold-pressed rapeseed oil. A "positive control" (PC) showing the
      desired sensory attributes and an oil eliciting a fusty/musty off-flavor (OF)
      were analyzed. Comparative aroma extract dilution analysis (cAEDA),
      identification experiments, quantitation by stable isotope dilution assays
      (SIDAs), calculation of odor activity values (OAVs), and aroma recombination
      resulted in 11 odorants with an OAV >= 1 in PC. Main differences between both
      oils were obtained for compounds caused by microbial influence revealing
      significantly higher concentrations in OF, e.g., for ethyl 2-methylbutanoate, 2
      methoxyphenol, 3-hydroxy-4,5-dimethylfuran-2(5H)-one (sotolon), 2- and 3
      methylbutanoic acid, and 4-methylphenol. Comparison of the key odorants in OF
      with those of the rapeseeds (OFS), from which it was pressed, showed the same 18
      compounds proving that the grade of the seeds and their storage conditions are
      important criteria for the quality of the final oil. Finally, a further 7 native
      cold-pressed rapeseed oils, eliciting the same sensory defect, were analyzed to
      confirm aroma-active marker compounds responsible for the fusty/musty off-flavor.

PMID- 27712067
TI  - Hollow Nano- and Microstructures as Catalysts.
AB  - Catalysis is at the core of almost every established and emerging chemical
      process and also plays a central role in the quest for novel technologies for the
      sustainable production and conversion of energy. Particularly since the early
      2000s, a great surge of interest exists in the design and application of micro-
      and nanometer-sized materials with hollow interiors as solid catalysts. This
      review provides an updated and critical survey of the ever-expanding material
      architectures and applications of hollow structures in all branches of catalysis,
      including bio-, electro-, and photocatalysis. First, the main synthesis
      strategies toward hollow materials are succinctly summarized, with emphasis on
      the (regioselective) incorporation of various types of catalytic functionalities
      within their different subunits. The principles underlying the scientific and
      technological interest in hollow materials as solid catalysts, or catalyst
      carriers, are then comprehensively reviewed. Aspects covered include the
      stabilization of catalysts by encapsulation, the introduction of molecular
      sieving or stimuli-responsive "auxiliary" functionalities, as well as the single
      particle, spatial compartmentalization of various catalytic functions to create
      multifunctional (bio)catalysts. Examples are also given on the applications which
      hollow structures find in the emerging fields of electro- and photocatalysis,
      particularly in the context of the sustainable production of chemical energy
      carriers. Finally, a critical perspective is provided on the plausible evolution
      lines for this thriving scientific field, as well as the main practical
      challenges relevant to the reproducible and scalable synthesis and utilization of
      hollow micro- and nanostructures as solid catalysts.

PMID- 27712068
TI  - Stable Graphene-Isolated-Au-Nanocrystal for Accurate and Rapid Surface
      Enhancement Raman Scattering Analysis.
AB  - Various interferences from measurement conditions and substrate inhomogeneity are
      well-known confounding factors for poor reproducibility, which is a challenge in
      surface-enhanced Raman scattering (SERS) quantification. To address these issues,
      novel substrates and versatile internal standards have been designed and the
      repeatability is improved to some degree. However, these internal standards are
      either complex or unstable enough to resist harsh environments such as acid and
      oxidation. Graphene-isolated-Au-nanocrystal (GIAN) has unique properties and been
      applied for cell multimodal imaging and chemotherapy but not for SERS
      quantification analysis yet. Herein, we chose GIANs to improve the accuracy of
      SERS analysis. GIAN integrates the SERS effect and internal standard into a
      simple nanoparticle and is proved to be an ideal platform for SERS analysis given
      its superior properties: (1) chemical stability, it remains stable in strong acid
      and oxidation, even mimic bioenvironment; (2) a simple core-shell structure, with
      a thin graphitic shell which is not only a protector that avoiding inner Au
      catalysis unnecessary reaction but also an internal standard to eliminate the
      interference during the Raman detections; (3) the big-Pi structure can absorb
      target molecule thus achieve an enrichment effect and quench background
      fluorescence. Laser power, focus, and substrate fluctuations as well as coexist
      substance interferences were investigated and the accuracy was improved greatly
      with the introduction of 2D band internal standard in Raman silent region with
      less background. Moreover, GIAN was applied for crystal violet determination
      directly on fish muscle and scale, which was rapid and convenient without complex
      extraction process. All these results indicate GIAN is an optimum choice for SERS
      analysis in complex systems.

PMID- 27712069
TI  - Stable Disk Assemblies of a Tobacco Mosaic Virus Mutant as Nanoscale Scaffolds
      for Applications in Drug Delivery.
AB  - Current approaches to nanoscale therapeutic delivery rely on the attachment of a
      drug of interest to a nanomaterial scaffold that is capable of releasing the drug
      selectively in a tumor environment. One class of nanocarriers receiving
      significant attention is protein nanomaterials, which are biodegradable and
      homogeneous in morphology and can be equipped with multiple functional handles
      for drug attachment. Although most protein-based nanocarriers are spherical in
      morphology, recent research has revealed that nonspherical nanomaterials may have
      favorable tumor uptake in comparison to their spherical counterparts. It is
      therefore important to expand the number of nonspherical protein-based
      nanocarriers that are available. Herein, we report the development of a self
      assembling nanoscale disk derived from a double arginine mutant of recombinantly
      expressed tobacco mosaic virus coat protein (RR-TMV). RR-TMV disks display highly
      stable double-disk assembly states. These RR-TMV disks were functionalized with
      the chemotherapy drug doxorubicin (DOX) and further modified with polyethylene
      glycol (PEG) for improved solubility. RR-TMVDOX-PEG displayed cytotoxic
      properties similar to those of DOX alone when incubated with U87MG glioblastoma
      cells, but unmodified RR-TMV did not cause any cytotoxicity. The RR-TMV disk
      assembly represents a promising protein-based nanomaterial for applications in
      drug delivery.

PMID- 27712070
TI  - Molecular Dynamics Simulations Predict the Pathways via Which Pristine Fullerenes
      Penetrate Bacterial Membranes.
AB  - Carbon fullerenes are emerging as effective devices for different biomedical
      applications, including the transportation of nanosized drugs and extraction of
      harmful oxidants and radicals. It has been proposed that fullerenes could be used
      as novel antibacterial agents, given the realization that the nanoparticles can
      kill pathogenic Gram-negative bacteria. To explore this at the molecular level,
      we simulated C60 fullerenes with bacterial membranes using the coarse-grain
      molecular dynamics Martini force field. We found that pristine C60 has a limited
      tendency to penetrate (incomplete core) Re mutant lipopolysaccharide (LPS)
      leaflets, but the translocation of C60 fullerenes into (complete core) Ra mutant
      LPS leaflets is not thermodynamically favored. Moreover, we showed that the
      permeability of the Re LPS bilayers depends sensitively on the system
      temperature, charge of ambient ions, and prevalence of
      palmitoyloleoylphosphoethanolamine (POPE) defect domains. The different
      permeabilities are rationalized in terms of transitory head group pore formation,
      which underpins the translocation of C60 into the lipid core. The Re LPS lipids
      readily form transient micropores when they are linked with monovalent cations or
      when they are heated to a high temperature. POPE lipids are shown to be
      particularly adept at forming these transient surface cavities, and their
      inclusion into Re LPS membranes facilitates the formation of particularly large
      pores that are tunneled by C60 aggregates of a significant size (~5 nm wide).
      After insertion into the lipid core, the aggregates dissociate, and the disbanded
      nanoparticles migrate to the interface between separate POPE and LPS domains,
      where they weaken the boundaries between the coexisting lipid fractions and
      thereby promote lipid mixing.

PMID- 27712071
TI  - Tetraazacalix[2]arence[2]triazine Coated Fe3O4/SiO2 Magnetic Nanoparticles for
      Simultaneous Dispersive Solid Phase Extraction and Determination of Trace
      Multitarget Analytes.
AB  - To satisfy the requirement of simultaneous extraction and characterization of
      diverse kinds of multitarget analytes, the preparation, characterization, and
      application of a novel tetraazacalix[2]arene[2]triazine (TCT) coated magnetic
      nanoparticle (TCT MNP) adsorbent are presented in this paper. TCT assembles two
      benzene rings and two triazines with nitrogen cross-bridging links, which
      exhibits a unique structural framework and versatile recognition features based
      on the multiple recognition sites. These include pi electron stacking, charge
      transfer, hydrogen bonding, and ion-exchange. TCT MNPs acted as a dispersive SPE
      adsorbent showing strong interaction with and adsorption of polycyclic aromatic
      hydrocarbons (PAHs), nitroaromatics, and heavy metal ions. The dispersive
      magnetic nanoparticle solid phase extraction (d-MNSPE) strategy with the
      simultaneous extraction and stepwise elution (SESE) procedure was designed and
      optimized for the five PAHs (phenanthrene, anthracene, pyrene, chrysene, and
      benzo(a)pyrene), six nitroaromatics (4-nitrotoluene, 2,4-dinitrotoluene, 2,4,6
      trinitrotoluene, 4-nitrophenol, 2,4-dinitrophenol, and 2,4,6-trinitrophenol), and
      four metal ions (Cu, Zn, Mn, Cd) in aqueous samples. Due to the high stability,
      desirable durability, larger saturation magnetization, reuse and distinct
      enrichment capacity of TCT MNPs, the d-MNSPE method with the SESE strategy
      provided high recovery (>90%) and good precision (relative standard deviations,
      RSD < 10%). Coupled with the commonly used HPLC-fluorescence detection, HPLC-UV
      detection, and atomic absorption spectrometry, these trace probes in tap water,
      river water, and lake water were determined with very low detection limits, in
      the range of 0.09-0.15 pg mL-1 for PAHs, 6-11 pg mL-1 for nitroaromatics, and 17
      53 pg mL-1 for metal ions after being enriched by the d-MNSPE. The determination
      of trace PAHs in urine samples from smokers and nonsmokers was successfully
      carried out with this method, which implied that the versatile TCT MNPs and the
      robust method together represent a significant potential application in the
      analysis of body fluids and disease markers. Such methods for accurate
      quantification of trace components in water are very valuable as they fulfill an
      unmet need in environmental and medicinal chemistry.

PMID- 27712072
TI  - Computational Study of Reduction Potentials of Th4+ Compounds and Hydrolysis of
      ThO2(H2O)n, n = 1, 2, 4.
AB  - The stability of Th4+ to reduction in water is studied by DFT methods. The
      standard reduction potential (SRP) of homoleptic complexes including Th(H2O)94+,
      Th(H2O)104+, Th(NO3)4, Th(NO2)62-, Th(NO3)62-, Th(COT)2, Th(acac)4, ThCp4, ThF4,
      and ThCl4 have been investigated. The values vary widely (from -3.50 V for
      Th(OH)4 to -0.62 V for Th(NO3)4 depending on whether the ligands are redox active
      (noninnocent) or not. Several additional topics of thorium chemistry are
      explored, including the hydrolysis mechanism of ThO2(H2O)n, n = 1, 2, 4, and the
      solution phase nonzero dipole moment of ThCp4. Dinuclear complexes are also
      characterized, including Th2O4, Th2O2(OH)4, Th2O2(H2O)8, Th2(OH)8(H2O)4, and
      Th2(OH)2(NO3)6(H2O)4 and condensed thorium complexes as [Th4(OH)6(H2O)12]10+ and
      [Th6(OH)14(H2O)12]10+. For the Th2(OH)2(NO3)6(H2O)4 dinuclear complex, the first
      SRP is -0.82 V and the second is 1.59 V. The first SRP corresponds to the
      reduction of the ligand NO3-, and the second SRP corresponds to dissociative
      electron transfer to the NO32- ligand. The calculated formation constant of
      Th(EDTA)(H2O)4 is in reasonable agreement with experiment. The different
      stereochemistries of the bidentate ligands NO2-, NO3-, and acetylacetonate (acac)
      around the thorium center have very similar stabilities.

PMID- 27712074
TI  - ATP Hydrolysis Mechanism in a Maltose Transporter Explored by QM/MM Metadynamics
      Simulation.
AB  - Translocation of substrates across the cell membrane by adenosine 5'-triphosphate
      (ATP)-binding cassette (ABC) transporters depends on the energy provided by ATP
      hydrolysis within the nucleotide-binding domains (NBDs). However, the detailed
      mechanism remains unclear. In this study, we focused on maltose transporter NBDs
      (MalK2) and performed a quantum mechanical/molecular mechanical (QM/MM) well
      tempered metadynamics simulation to address this issue. We explored the free
      energy profile along an assigned collective variable. As a result, it was
      determined that the activation free energy is approximately 10.5 kcal/mol, and
      the reaction released approximately 3.8 kcal/mol of free energy, indicating that
      the reaction of interest is a one-step exothermic reaction. The dissociation of
      the ATP gamma-phosphate seems to be the rate-limiting step, which supports the so
      called dissociative model. Moreover, Glu159, located in the Walker B motif, acts
      as a base to abstract the proton from the lytic water, but is not the catalytic
      base, which corresponds to an atypical general base catalysis model. We also
      observed two interesting proton transfers: transfer from the His192 epsilon
      position nitrogen to the dissociated inorganic phosphate, Pi, and transfer from
      the Lys42 side chain to adenosine 5'-diphosphate beta-phosphate. These proton
      transfers would stabilize the posthydrolysis state. Our study provides
      significant insight into the ATP hydrolysis mechanism in MalK2 from a dynamical
      viewpoint, and this insight would be applicable to other ABC transporters.

PMID- 27712073
TI  - Highly Stable Fluorinated Nanocarriers with iRGD for Overcoming the Stability
      Dilemma and Enhancing Tumor Penetration in an Orthotopic Breast Cancer.
AB  - The stability dilemma and limited tumor penetration of nanocarriers in cancer
      chemotherapy remain two predominant challenges for their successful clinical
      translation. Herein, the pH-sensitive fluorocarbon-functionalized nanocarriers
      (SFNs) with a tumor-homing and penetrating peptide iRGD are reported to overcome
      the stability dilemma and enhance tumor accumulation and penetration in an
      orthotopic breast cancer. The highly stable SFNs with a low critical association
      concentration provide a safe and spacious harbor for hydrophobic drugs.
      Furthermore, the stimulus-responsive evaluation and in vitro drug release study
      show that the SFNs can balance intracellular dissociation for drug release and
      extracellular stability in the blood circulation. Additionally, the tumor
      penetration capacity has been dramatically enhanced in 3D multicellular
      spheroids, effectively affecting cells far from the periphery. This can be
      ascribed to the coadministration of iRGD having tumor-penetrating ability and
      fluorocarbon chains having good cell membrane permeability. The combination of
      SFNs and iRGD is a viable approach to assist drugs' effective accumulation in
      primary and metastasized tumor sites, significantly inhibiting the breast tumor
      growth and curbing lung and liver metastases in an orthotopic-tumor-bearing mouse
      model. Taken together, this pH-sensitive fluorinated nanosystem having excellent
      stability and tumor accumulation and penetration properties paves the way to
      combat cancer.

PMID- 27712075
TI  - Ferromagnetic/Nonmagnetic Nanostructures for the Electrical Measurement of the
      Spin Hall Effect.
AB  - Spin-orbitronics is based on the ability of spin-orbit interactions to achieve
      the conversion between charge currents and pure spin currents. As the precise
      evaluation of the conversion efficiency becomes a crucial issue, the need for
      straightforward ways to observe this conversion has emerged as one of the main
      challenges in spintronics. Here, we propose a simple device, akin to the
      ferromagnetic/nonmagnetic bilayers used in most spin-orbit torques experiments,
      and consisting of a spin Hall effect wire connected to two transverse
      ferromagnetic electrodes. We show that this system allows probing electrically
      the direct and inverse conversion in a spin Hall effect system and measuring both
      the spin Hall angle and the spin diffusion length. By applying this method to
      several spin Hall effect materials (Pt, Pd, Au, Ta, W), we show that it
      represents a promising tool for the metrology of spin-orbit materials.

PMID- 27712076
TI  - Nanoscale Coordination Polymers Codeliver Carboplatin and Gemcitabine for Highly
      Effective Treatment of Platinum-Resistant Ovarian Cancer.
AB  - Due to the ability of ovarian cancer (OCa) to acquire drug resistance, it has
      been difficult to develop efficient and safe chemotherapy for OCa. Here, we
      examined the therapeutic use of a new self-assembled core-shell nanoscale
      coordination polymer nanoparticle (NCP-Carbo/GMP) that delivers high loadings of
      carboplatin (28.0 +/- 2.6 wt %) and gemcitabine monophosphate (8.6 +/- 1.5 wt %).
      A strong synergistic effect was observed between carboplatin and gemcitabine
      against platinum-resistant OCa cells, SKOV-3 and A2780/CDPP, in vitro. The
      coadministration of carboplatin and gemcitabine in the NCP led to prolonged blood
      circulation half-life (11.8 +/- 4.8 h) and improved tumor uptake of the drugs
      (10.2 +/- 4.4% ID/g at 24 h), resulting in 71% regression and 80% growth
      inhibition of SKOV-3 and A2780/CDDP tumors, respectively. Our findings
      demonstrate that NCP particles provide great potential for the codelivery of
      multiple chemotherapeutics for treating drug-resistant cancer.

PMID- 27712077
TI  - PEGylation of Reduced Graphene Oxide Induces Toxicity in Cells of the Blood-Brain
      Barrier: An in Vitro and in Vivo Study.
AB  - Polyethylene glycol (PEG) coating has been frequently used to improve the
      pharmacokinetic behavior of nanoparticles. Studies that contribute to better
      unravel the effects of PEGylation on the toxicity of nanoparticle formulation are
      therefore highly relevant. In the present study, reduced graphene oxide (rGO) was
      functionalized with PEG, and its effects on key components of the blood-brain
      barrier, such as astrocytes and endothelial cells, were analyzed in culture and
      in an in vivo rat model. The in vitro studies demonstrated concentration
      dependent toxicity. The highest concentration (100 MUg/mL) of non-PEGylated rGO
      had a lower toxic influence on cell viability in primary cultures of astrocytes
      and rat brain endothelial cells, while PEGylated rGO induced deleterious effects
      and cell death. We assessed hippocampal BBB integrity in vivo by evaluating
      astrocyte activation and the expression of the endothelial tight and adherens
      junctions proteins. From 1 h to 7 days post-rGO-PEG systemic injection, a notable
      and progressive down-regulation of protein markers of astrocytes (GFAP, connexin
      43), the endothelial tight (occludin), and adherens (beta-catenin) junctions and
      basal lamina (laminin) were observed. The formation of intracellular reactive
      oxygen species demonstrated by increases in the enzymatic antioxidant system in
      the PEGylated rGO samples was indicative of oxidative stress-mediated damage.
      Under the experimental conditions and design of the present study the PEGylation
      of rGO did not improve interaction with components of the blood-brain barrier. In
      contrast, the attachment of PEG to rGO induced deleterious effects in comparison
      with the effects caused by non-PEGylated rGO.

PMID- 27712078
TI  - Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas
      gingivalis.
AB  - Porphyromonas gingivalis is an oral pathogen associated with the inflammatory
      disease periodontitis. Periodontitis and P. gingivalis have been associated with
      rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of
      tolerance against citrullinated proteins. Citrullination is a post-translational
      modification of arginine residues, leading to a change in structure and function
      of the respective protein. This modification, which is catalyzed by
      peptidylarginine deiminases (PADs), plays a role in several physiological
      processes in the human body. Interestingly, P. gingivalis secretes a
      citrullinating enzyme, known as P. gingivalis PAD (PPAD), which targets bacterial
      and human proteins. Because the extent of P. gingivalis protein citrullination by
      PPAD was not yet known, the present study was aimed at identifying the
      extracellular proteome and citrullinome of P. gingivalis. To this end,
      extracellular proteins of two reference strains, two PPAD-deficient mutants, and
      three clinical isolates of P. gingivalis were analyzed by mass spectrometry. The
      results uncovered substantial heterogeneity in the extracellular proteome and
      citrullinome of P. gingivalis, especially in relation to the extracellular
      detection of typical cytoplasmic proteins. In contrast, the major virulence
      factors of P. gingivalis were identified in all investigated isolates, although
      their citrullination was shown to vary. This may be related to post-translational
      processing of the PPAD enzyme. Altogether, our findings focus attention on the
      possible roles of 6 to 25 potentially citrullinated proteins, especially the
      gingipain RgpA, in periodontitis and rheumatoid arthritis.

PMID- 27712079
TI  - Orthogonal Bodipy Trimers as Photosensitizers for Photodynamic Action.
AB  - Orthogonally linked BODIPY units show exceptional intersystem crossing
      efficiencies. We now report orthogonal BODIPY trimers with strong absorption in
      the visible region and high singlet oxygen generation capability. The X-ray
      diffraction structure confirms that the two peripheral BODIPY units are at a
      perpendicular angle to the core structure.

PMID- 27712080
TI  - Diet, the intestinal microbiota, and immune health in aging.
AB  - Many countries are facing aging populations, with those over 65 years of age
      likely to represent the largest population over the next 10-20 years. Living
      longer often comes with poor health and, in particular, a decline in the immune
      function characterized by poor vaccine responses and increased risk of infection
      and certain cancers. Aging and diet represent major intrinsic and extrinsic
      factors that influence the makeup and activity of resident intestinal microbes,
      the microbiota, the efficient functioning of which is essential for sustaining
      overall health and the effectiveness of the immune system. The provision of
      elderly specific dietary recommendations appears to be lacking but is necessary
      since this population has an altered microbiota and immune response and may not
      respond in the same way as their healthy and younger counterparts. We have
      reviewed the evidence supporting the role of diet and, in particular, dietary
      carbohydrate, protein, and fat in influencing the microbiota and its generation
      of key metabolites that influence the efficient functioning of immune cells
      during aging, and how dietary intervention might be of benefit in improving the
      intestinal health and immune status in the elderly.

PMID- 27712082
TI  - Fit-for-purpose biomarker immunoassay qualification and validation: three case
      studies.
AB  - AIM: To improve on the efficiency of biomarker assay readiness, and for reliable
      biomarker data to support three drug programs, we implemented a fit-for-purpose
      approach, qualifying two biomarker assays and validating a third.
      Results/methodology: The qualification strategy and selection of experiments for
      two exploratory biomarkers (CXCL1, CCL19) was determined by the intended use of
      the biomarker data. The third biomarker, IL-6, was validated as the data would be
      used in monitoring patient safety during dose-escalation studies in a Phase I
      trial. All three assays passed a priori acceptance criteria. CONCLUSION: These
      assays highlight strategies and methodologies for a fit-for-purpose approach.
      Minimum qualification, full qualification and validation were chosen and
      supported programs at different stages of drug development.

PMID- 27712081
TI  - 2016 White Paper on recent issues in bioanalysis: focus on biomarker assay
      validation (BAV) (Part 1 - small molecules, peptides and small molecule
      biomarkers by LCMS).
AB  - The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place in
      Orlando, Florida with participation of close to 700 professionals from
      pharmaceutical/biopharmaceutical companies, biotechnology companies, contract
      research organizations, and regulatory agencies worldwide. WRIB was once again a
      5-day, weeklong event - A Full Immersion Week of Bioanalysis including Biomarkers
      and Immunogenicity. As usual, it was specifically designed to facilitate sharing,
      reviewing, discussing and agreeing on approaches to address the most current
      issues of interest including both small and large molecule analysis involving
      LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and
      immunogenicity. This 2016 White Paper encompasses recommendations emerging from
      the extensive discussions held during the workshop, and is aimed to provide the
      bioanalytical community with key information and practical solutions on topics
      and issues addressed, in an effort to enable advances in scientific excellence,
      improved quality and better regulatory compliance. This white paper is published
      in 3 parts due to length. This part (Part 1) discusses the recommendations for
      small molecules, peptides and small molecule biomarkers by LCMS. Part 2 (Hybrid
      LBA/LCMS and regulatory inputs from major global health authorities) and Part 3
      (large molecule bioanalysis using LBA, biomarkers and immunogenicity) will be
      published in the Bioanalysis journal, issue 23.

PMID- 27712083
TI  - Aortic valve leaflet wall shear stress characterization revisited: impact of
      coronary flow.
AB  - Computational characterizations of aortic valve hemodynamics have typically
      discarded the effects of coronary flow. The objective of this study was to
      complement our previous fluid-structure interaction aortic valve model with a
      physiologic coronary circulation model to quantify the impact of coronary flow on
      aortic sinus hemodynamics and leaflet wall shear stress (WSS). Coronary flow
      suppressed vortex development in the two coronary sinuses and altered WSS
      magnitude and directionality on the three leaflets, with the most substantial
      differences occurring in the belly and tip regions.

PMID- 27712084
TI  - Hope and social support in elderly patients with cancer and their partners: an
      actor-partner interdependence model.
AB  - AIM: Assess relationships between oldest-old (minimum 86 years) patients'
      perceived social support to their own and their spousal caregivers' hope through
      application of the actor-partner interdependence model (APIM). PATIENTS &
      METHODS: 58 dyads of patients and their spousal caregivers completed standardized
      self-report measures of depression, distress, hope and social support. RESULTS:
      Patients presented high distress levels. Among patients and spouses, perceived
      social support was positively correlated to their own level of hope (beta = 0.44,
      p < 0.0001; beta = 0.56, p < 0.0001, respectively) and negatively correlated to
      the other's level of hope (beta = -0.25, p < 0.024; beta = -0.44, p < 0.0001,
      respectively). CONCLUSION: The actor-partner interdependence model was found to
      be adequate for describing relationships between social support and hope among
      dyads of oldest-old patients and their spousal caregivers. Patients and caregiver
      seem to utilize social support to enhance hope.

PMID- 27712085
TI  - 'They've invited me into their world': a focus group with clinicians delivering a
      behaviour change intervention in a UK contraceptive service.
AB  - Although teenage conceptions rates in the United Kingdom (UK) have seen a
      downward trend recently, it remains imperative that contraceptive services for
      young people continue to improve. To ensure that evidence-based interventions are
      sustained in clinical practice, it is useful to assess the experiences of those
      delivering them. This study explores the experiences of sexual health clinicians
      who were trained to deliver a one-to-one behaviour change intervention aiming to
      improve contraceptive use in young women. The intervention was set in a UK NHS
      contraceptive and sexual health service and involved clinicians' facilitating
      (within one-to-one consultations) the formation of implementation intentions (or
      'if-then' plans) that specified when, where and how young women would use
      contraception. A focus group was conducted with seven clinicians who had
      delivered the intervention. A thematic analysis of the focus group revealed three
      overall themes: (1) How the intervention worked in practice; (2) barriers and
      benefits to delivering the intervention; and (3) positive changes to individual
      consultation style and wider 'best practice' within the clinic. Our findings show
      that, with support, clinical staff would be in favour of incorporating if-then
      planning as a strategy to help promote contraceptive adherence in young women.

PMID- 27712086
TI  - Evaluation and selection of a non-PCR based technology for improved gene
      expression profiling from clinical formalin-fixed, paraffin-embedded samples.
AB  - AIM: Formalin-fixed, paraffin-embedded (FFPE) clinical tissue samples have the
      potential to provide valuable gene-expression data for the development of cancer
      biomarkers. However, FFPE RNA is extensively fragmented, presenting a significant
      challenge for reliably detecting gene expression using traditional qPCR methods.
      RESULTS: We evaluated three novel methodologies along with the traditional qPCR
      method for their ability to detect Notch pathway gene expression in colorectal
      cancer FFPE tissue RNAs. We found that quantitative nuclease protection assay
      detected gene expression in high-quality RNAs as sensitively as qPCR, and
      consistently detected mRNAs in highly fragmented FFPE tissue RNAs. CONCLUSION:
      Quantitative nuclease protection assay represents an improved methodology for
      detecting gene expression in FFPE tissue and has the potential to advance the
      development of cancer biomarkers.

PMID- 27712087
TI  - Development and validation of an IA-LC/MS method to quantitate active and total B
      type natriuretic peptide in human plasma.
AB  - AIM: Patients with elevated levels of B-type natriuretic peptide (BNP) and/or NT
      proBNP as measured by clinical tests have an elevated risk of heart failure (HF).
      Despite utility in large clinical studies, both assays are plagued by large
      biological variability and specificity issues. To address these concerns and
      further investigate BNP in the HF setting, we developed an LC/MS assay to
      characterize the ratio of active to total BNP. RESULTS: We have developed and
      validated a novel immunoaffinity LC/MS assay to measure BNP-derived fragments, as
      well as 'total BNP' in human plasma. The ratio of active BNP1-32 to total BNP in
      11 HF subjects was found to be <8%, and the sum of detectable BNP fragments
      contributed approximately 20% of total BNP. CONCLUSION: We developed an assay
      with the specificity to measure the active form of BNP, which may aid in the
      accurate diagnosis and better management of HF.

PMID- 27712088
TI  - Are school meals a viable and sustainable tool to improve the healthiness and
      sustainability of children's diet and food consumption? A cross-national
      comparative perspective.
AB  - There is little agreement among governments, institutions, scientists and food
      activists as to how to best tackle the challenging issues of health and
      sustainability in the food sector. This essay discusses the potential of school
      meals as a platform to promote healthy and sustainable food behavior. School meal
      programs are of particular interest for improving public diet because they reach
      children at a population scale across socio-economic classes and for over a
      decade of their lives, and because food habits of children are more malleable
      than those of adults. Current research on the history and health implications of
      school meal programs is reviewed in a cross-national comparative framework, and
      arguments explored that speak for the need of a new developmental phase of school
      meals as an integrative learning platform for healthy and sustainable food
      behavior. Nutritional, social, practical, educational, economical, political, and
      cultural perspectives and challenges linked to the implementation of healthy and
      sustainable school meals are discussed. Finally, the need for long-term
      interventions and evaluations is highlighted and new research directions are
      proposed.

PMID- 27712089
TI  - Tolerance and hyperaccumulation of a mixture of heavy metals (Cu, Pb, Hg, and Zn)
      by four aquatic macrophytes.
AB  - In the present investigation, four macrophytes, namely Typha latifolia (L.),
      Lemna minor (L.), Eichhornia crassipes (Mart.) Solms-Laubach, and Myriophyllum
      aquaticum (Vell.) Verdc, were evaluated for their heavy metal (Cu, Pb, Hg, and
      Zn) hyperaccumulation potential under laboratory conditions. Tolerance analyses
      were performed for 7 days of exposure at five different treatments of the metals
      mixture (Cu+2, Hg+2, Pb+2, and Zn+2). The production of chlorophyll and
      carotenoids was determined at the end of each treatment. L. minor revealed to be
      sensitive, because it did not survive in all the tested concentrations after 72
      hours of exposure. E. crassipes and M. aquaticum displayed the highest tolerance
      to the metals mixture. For the most tolerant species of aquatic macrophytes, The
      removal kinetics of E. crassipes and M. aquaticum was carried out, using the
      following mixture of metals: Cu (0.5 mg/L) and Hg, Pb, and Zn 0.25 mg/L. The
      obtained results revealed that E. crassipes can remove 99.80% of Cu, 97.88% of
      Pb, 99.53% of Hg, and 94.37% of Zn. M. aquaticum withdraws 95.2% of Cu, 94.28% of
      Pb, 99.19% of Hg, and 91.91% of Zn. The obtained results suggest that these two
      species of macrophytes could be used for the phytoremediation of this mixture of
      heavy metals from the polluted water bodies.

PMID- 27712090
TI  - Use of horizontal subsurface flow constructed wetlands to treat reverse osmosis
      concentrate of rolling wastewater.
AB  - According to the characteristics of the reverse osmosis concentrate (ROC)
      generated from iron and steel company, we used three sets of parallel horizontal
      subsurface flow (HSF) constructed wetlands (CWs) with different plants and
      substrate layouts to treat the high-salinity wastewater. The plant growth and
      removal efficiencies under saline condition were evaluated. The evaluation was
      based entirely on routinely collected water quality data and the physical and
      chemical characteristics of the plants (Phragmites australis, Typha latifolia,
      Iris wilsonii, and Scirpus planiculmis). The principal parameters of concern in
      the effluent were chemical oxygen demand (COD), total nitrogen (TN), and total
      phosphorus (TP). The results showed that the CWs were able to remove COD, TN, and
      TP from ROC. S. planiculmis was not suitable for the treatment of high-saline
      wastewater. The sequence of metals accumulated in CW plants was K>Ca>Na>Mg>Zn>Cu.
      More than 70% of metals were accumulated in the aboveground of P. australis. The
      CW filled with gravel and manganese ore and planted with P. australis and T.
      latifolia had the best performance of pollutant removal, with average removal of
      49.96%, 39.45%, and 72.01% for COD, TN, and TP, respectively. The effluent water
      quality met the regulation in China. These results suggested that HSF CW planted
      with P. australis and T. latifolia can be applied for ROC pollutants removal.

PMID- 27712091
TI  - Sustained high-pressure in the spinal subarachnoid space while arterial expansion
      is low may be linked to syrinx development.
AB  - Syringomyelia (a spinal cord cyst) usually develops as a result of conditions
      that cause cerebrospinal fluid (CSF) obstruction. The mechanism of syrinx
      formation and enlargement remains unclear, though previous studies suggest that
      the fluid enters via the perivascular spaces (PVS) of the penetrating arteries of
      the spinal cord, and that alterations in the CSF pulse timing and pressure could
      contribute to enhanced PVS inflow. This study uses an idealised computational
      model of the PVS to investigate the factors that influence peri-arterial fluid
      flow. First, we used three sample patient-specific models to explore whether
      changes in subarachnoid space (SAS) pressures in individuals with and without
      syringomyelia could influence PVS inflow. Second we conducted a parametric study
      to determine how features of the CSF pulse altered perivascular fluid, including
      alterations to timing and magnitude of the peak SAS pressure, the timing of
      reversal from high to low pressure (diastolic phase), and the area under the
      pressure-time curve. The model for the patient with syringomyelia had higher net
      CSF inflow to the PVS than the two subjects without syringomyelia. In the
      parametric study, only increasing the area under the high pressure region of the
      SAS pulse substantially increased PVS inflow, when coupled with a temporal shift
      in arterial and SAS pulses. This suggests that a period of sustained high SAS
      pressure while arterial diameter is low may increase net CSF pumping into the
      PVS.

PMID- 27712092
TI  - Uniportal video-assisted thoracic surgery or single-incision video-assisted
      thoracic surgery for lung resection: clarifying definitions.

PMID- 27712093
TI  - Addressing taxane resistance in metastatic castration-resistant prostate cancer:
      a focus on chaperone proteins.
AB  - Despite the significant survival benefit of taxane therapy in metastatic
      castration-resistant prostate cancer (mCRPC), all patients inevitably develop
      treatment resistance. An understanding of resistance mechanisms has led to new
      therapies for prostate cancer (cabazitaxel, abiraterone and enzalutamide), all of
      which have improved survival following first-line docetaxel. Another treatment,
      currently in development, targets the prosurvival molecule clusterin. Custirsen,
      an antisense molecule that inhibits clusterin production, has shown promise in
      combination with docetaxel in mCRPC patients at risk for poor outcomes. Although
      optimal sequence and combination of available therapies is unclear, the
      heterogeneity of mCRPC suggests a continuing need for personalized treatment
      regimens and improved abilities to predict which patients will respond to the
      available treatment options.

PMID- 27712094
TI  - Relationship between daily training load and psychometric status of professional
      soccer players.
AB  - We studied the relationship between daily training load (TL) experienced by
      professional soccer players and the Hooper questionnaire reflecting their
      perceived quality of sleep, fatigue, stress and delayed onset muscle soreness.
      During a 16-week training period, the rating of perceived exertion and duration
      were collected after each training session, and daily TL was calculated from 14
      professional soccer players. The Hooper questionnaire was completed every day
      before the first training session and the Hooper's score (HS) was then
      calculated. The daily TL and HS were 379.9 +/- 198.3 AU and 16.2 +/- 5.1,
      respectively. Pearson correlation showed significant relationships (p < 0.01)
      between TL and perceived fatigue, muscle soreness, sleep and stress. Our findings
      revealed that the perceived sleep, stress, fatigue and muscle soreness are
      moderately related to the daily TL in professional soccer players. The Hooper
      questionnaire is both a simple and useful tool for monitoring perceived wellness
      and psychometric players' status of professional soccer players.

PMID- 27712095
TI  - Predicting dental attendance from dental hygienists' autonomy support and
      patients' autonomous motivation: A randomised clinical trial.
AB  - OBJECTIVE: To test the hypothesis that a Self-Determination Theory (SDT)
      intervention designed to promote oral health care competence in an autonomy
      supportive way would predict change in caries competence relative to standard
      care. Further, to test the SDT process path-model hypotheses with: (1) the
      intervention and individual differences in relative autonomous locus of causality
      (RALOC) predicting increases in caries competence, which in turn would positively
      predict dental attendance; (2) RALOC negatively predicting dental anxiety, which
      would negatively predict dental attendance; (3) RALOC and caries disease referred
      to the dentist after an autonomy-supportive clinical exam directly positively
      predicting dental attendance; and (4) the intervention moderating the link
      between RALOC and dental attendance. DESIGN: A randomised two-group experiment
      was conducted at a dental clinic with 138 patients (Mage = 23.31 yr., SD = 3.5),
      with pre- and post-measures in a period of 5.5 months. RESULTS: The experimental
      model was supported. The SDT path model fit the data well and supported the
      hypotheses explaining 63% of the variance in dental attendance. CONCLUSIONS:
      Patients personality (RALOC) and hygienists promoting oral health care competence
      in an autonomy-supportive way, performance of autonomy-supportive clinical exams
      and reductions of anxiety for dental treatment have important practical
      implications for patients' dental attendance.

PMID- 27712096
TI  - Guardians' Perceptions of Dogs' Welfare and Behaviors Related to Visiting the
      Veterinary Clinic.
AB  - A large survey of Italian dog guardians (n = 906) was conducted to assess dog
      behavior and welfare at the veterinary clinic and to investigate how guardians
      and veterinarians affect them. This study confirmed that the veterinary clinic is
      a source of stress for most dogs, who showed impaired welfare in all phases: in
      the waiting room, entering the examination room, on the examination table, and
      when approached by the vet. This study also characterizes some factors related to
      the guardians' and veterinarians' behavior that affect the dogs' behavior and
      welfare during the veterinary examination. If dogs had not been examined by a vet
      since puppyhood, if they did not accept treatments by their guardians, and if
      they were scolded when refusing a treatment, the risk for having problems with
      dog welfare and behavior at the veterinary clinic increased. The attention paid
      by the vet to the dog was found to be positively related with a good response of
      the dog to the vet. Prevention seems to be the key for the protection of dog
      welfare related to veterinary care.

PMID- 27712097
TI  - In vitro evaluation of cytotoxic activity of the ethanol extract and isolated
      compounds from the corms of Liatris spicata (L.) willd on HepG2.
AB  - Investigation of the ethanol extract of the corms of Liatris spicata (L.) willd
      led to the isolation of two sterols: stigmasterol and its 3-O-glucoside, a
      triterpene: obtusifoliyl acetate, two benzofurans: euparin and 6-hydroxy-3
      methoxytremetone, three phenolic acids: protocatechuic, vanillic and ferulic acid
      and a sesquiterpene lactone igalan. The structures of the isolated compounds were
      established on the basis of physicochemical properties and spectral analysis (IR,
      EI/MS, 1H NMR and 13C NMR). The ethanol extract and its isolated compounds
      evidenced cytotoxic activities against human liver cancer cell line (HepG2),
      where igalan showed the highest potency (3.83 +/- 0.043) MUg/mL, its effect was
      comparable to that of the standard drug doxorubicin(r) (3.73 +/- 0.036) MUg/mL.

PMID- 27712100
TI  - Centennial Celebration: Endocrine Reviews Past Highlights for September and
      October.

PMID- 27712101
TI  - Hemodynamic Control of Endothelial Cell Fates in Development.
AB  - Biomechanical forces are emerging as critical regulators of embryogenesis,
      particularly in the developing cardiovascular system. From the onset of blood
      flow, the embryonic vasculature is continuously exposed to a variety of
      hemodynamic forces. These biomechanical stimuli are key determinants of vascular
      cell specification and remodeling and the establishment of vascular homeostasis.
      In recent years, major advances have been made in our understanding of mechano
      activated signaling networks that control both spatiotemporal and structural
      aspects of vascular development. It has become apparent that a major site for
      mechanotransduction is situated at the interface of blood and the vessel wall and
      that this process is controlled by the vascular endothelium. In this review, we
      discuss the hemodynamic control of endothelial cell fates, focusing on arterial
      venous specification, lymphatic development, and the endothelial-to-hematopoietic
      transition, and present some recent insights into the mechano-activated pathways
      driving these cell fate decisions in the developing embryo.

PMID- 27712103
TI  - Monitoring of pistachio (Pistacia Vera) ripening by high field nuclear magnetic
      resonance spectroscopy.
AB  - The metabolic profiling of pistachio (Pistacia vera) aqueous extracts from two
      different cultivars, namely 'Bianca' and 'Gloria', was monitored over the months
      from May to September employing high field NMR spectroscopy. A large number of
      water-soluble metabolites were assigned by means of 1D and 2D NMR experiments.
      The change in the metabolic profiles monitored over time allowed the pistachio
      development to be investigated. Specific temporal trends of amino acids, sugars,
      organic acids and other metabolites were observed and analysed by multivariate
      Partial Least Squares (PLS) analysis. Statistical analysis showed that while in
      the period from May to September there were few differences between the two
      cultivars, the ripening rate was different.

PMID- 27712102
TI  - TCR Signal Strength and T Cell Development.
AB  - Thymocyte selection involves the positive and negative selection of the
      repertoire of T cell receptors (TCRs) such that the organism does not suffer
      autoimmunity, yet has the benefit of the ability to recognize any invading
      pathogen. The signal transduced through the TCR is translated into a number of
      different signaling cascades that result in transcription factor activity in the
      nucleus and changes to the cytoskeleton and motility. Negative selection involves
      inducing apoptosis in thymocytes that express strongly self-reactive TCRs,
      whereas positive selection must induce survival and differentiation programs in
      cells that are more weakly self-reactive. The TCR recognition event is analog by
      nature, but the outcome of signaling is not. A large number of molecules regulate
      the strength of the TCR-derived signal at various points in the cascades. This
      review discusses the various factors that can regulate the strength of the TCR
      signal during thymocyte development.

PMID- 27712104
TI  - Assessment of Welfare Issues During Traditional Slaughter of Goats in Pretoria,
      South Africa.
AB  - Goats are traditionally slaughtered to celebrate marriages and births, venerate
      ancestors, address personal problems, or perform a ritual during funerals. The
      objective of this study was to assess nonhuman animal welfare issues associated
      with the traditional slaughter of goats in and around Pretoria, South Africa.
      Participatory research methods were used to interview 105 respondents. Four of
      those interviewed were visited to observe the slaughter process. The most common
      method of transport was a vehicle (47%), followed by transport on foot (30%). The
      distance traveled (68%) was usually less than 10 km, and in all cases, it was
      less than 50 km. The most common (57%) method of restraining goats during
      transport was tying all 4 legs together. During slaughter, assistants held the
      head and legs of the goat (55%). Prior to slaughter, the majority of goats were
      tied under a tree (66%). In total, 97% of the goats were slaughtered within 24
      hr, and no stunning was performed. In this study, animal welfare problems were
      widespread. Research should be undertaken to find practical ways to address
      animal welfare issues during traditional slaughter.

PMID- 27712106
TI  - A Pilot Study of Eight-Session Mindfulness-Based Cognitive Therapy Adapted for
      Women's Sexual Interest/Arousal Disorder.
AB  - While few treatment options exist for low sexual desire and arousal, the most
      common sexual dysfunction in women, a growing body of research supports the
      efficacy of mindfulness-based approaches. The mechanisms underlying improvements,
      and whether they are due to mindfulness practice or other treatment components,
      are unclear. As a result, we designed and pilot-tested an eight-session group
      mindfulness-based cognitive therapy for sexuality (MBCT-S) program that includes
      more extensive practice of mindfulness skills and closely aligns with the
      evidence-based MBCT program for depression and anxiety. A total of 26 women (mean
      age 43.9, range 25 to 63) with a diagnosis of sexual interest/arousal disorder
      participated in eight weekly group sessions, before and after which they
      completed validated questionnaires. The majority of women attended all sessions
      and completed the recommended at-home mindfulness exercises. Compared to
      baseline, women reported significant improvements in sexual desire, overall
      sexual function, and sex-related distress, regardless of treatment expectations,
      relationship duration, or low desire duration. Depressed mood and mindfulness
      also significantly improved and mediated increases in sexual function. These
      pilot data suggest that eight-session MBCT-S is feasible and significantly
      improves sexual function, and provide the basis for a larger randomized
      controlled trial (RCT) with a longer follow-up period.

PMID- 27712099
TI  - The Pathophysiologic Role of Disrupted Circadian and Neuroendocrine Rhythms in
      Breast Carcinogenesis.
AB  - Most physiological processes in the brain and body exhibit daily (circadian)
      rhythms coordinated by an endogenous master clock located in the suprachiasmatic
      nucleus of the hypothalamus that are essential for normal health and functioning.
      Exposure to sunlight during the day and darkness at night optimally entrains
      biological rhythms to promote homeostasis and human health. Unfortunately, a
      major consequence of the modern lifestyle is increased exposure to sun-free
      environments during the day and artificial lighting at night. Additionally,
      behavioral disruptions to circadian rhythms (ie, repeated transmeridian flights,
      night or rotating shift work, or sleep disturbances) have a profound influence on
      health and have been linked to a number of pathological conditions, including
      endocrine-dependent cancers. Specifically, night shift work has been identified
      as a significant risk factor for breast cancer in industrialized countries.
      Several mechanisms have been proposed by which shift work-induced circadian
      disruptions promote cancer. In this review, we examine the importance of the
      brain-body link through which circadian disruptions contribute to endocrine
      dependent diseases, including breast carcinogenesis, by negatively impacting
      neuroendocrine and neuroimmune cells, and we consider preventive measures
      directed at maximizing circadian health.

PMID- 27712105
TI  - Normative data for evaluating mild traumatic brain injury with a handheld
      neurocognitive assessment tool.
AB  - The BrainScope Ahead 300 is designed for use by health care professionals to aid
      in the assessment of patients suspected of a mild traumatic brain injury. The
      purpose of the current study was to establish normative data for the cognitive
      test component of the Ahead 300 system and to evaluate the role of demographic
      factors on test performance. Healthy, community-dwelling adults between the ages
      of 18 and 80 recruited from five geographically distributed sites were
      administered Android versions of the ANAM Matching to Sample and Procedural
      Reaction Time tests that comprise the cognitive test component of the Ahead 300
      system by trained personnel. Scores were correlated with age, education, and
      race. Age accounted for the majority of the variance in test scores with
      additional significant, but minor, contributions of education and race. Gender
      did not account for a significant proportion of the variance for either test.
      Based on these results, the normative data for 551 individuals are presented
      stratified by age. These are the first available normative data for these tests
      when administered using the Ahead 300 system and will assist health care
      professionals in determining the degree to which scores on the cognitive tests
      reflect impaired performance.

PMID- 27712107
TI  - Light Therapy With Scheduled Rise Times in Young Adults With Delayed Sleep Phase
      Disorder: Therapeutic Outcomes and Possible Predictors.
AB  - Clinical trials with light therapy (LT) for delayed sleep phase disorder (DSPD)
      are sparse and little is known about factors that are favorable for improvements.
      In this study, LT with scheduled rise times was conducted at home for 14 days by
      44 participants with DSPD aged 16-26 years. Primary outcomes were sleep onset and
      sleep offset. Potential predictors were demographic characteristics, chronotype,
      dim light melatonin onset, the number of days the LT lamp was used, the daily
      duration of LT, daytime sleepiness, anxiety, depression, worry, and rumination.
      Significant advances were observed in sleep onset and sleep offset from baseline
      to the end of treatment. The number of days of LT predicted earlier sleep onset
      and sleep offset.

PMID- 27712108
TI  - Sexual Behavior Latent Classes Among Men Who Have Sex With Men: Associations With
      Sexually Transmitted Infections.
AB  - Men who have sex with men (MSM) are at disproportionate risk of acquisition of
      sexually transmitted infections (STIs). We used latent class analysis (LCA) to
      examine patterns of sexual behavior among MSM and how those patterns are related
      to STIs. We examined patterns of sexual behavior using behavioral and clinical
      data from a cross-sectional study of 235 MSM who presented to an urban sexual
      health clinic for STI testing. Analyzed data were collected using a combination
      of interviewer- and self-administered surveys and electronic health records. We
      used LCA to identify underlying subgroups of men based on their sexual behavior,
      described the demographics of the latent classes, and examined the association
      between the latent classes and STI status. We identified three latent classes of
      sexual behavior: Unprotected Anal Intercourse (UAI) Only (67%), Partner Seekers
      (14%), and Multiple Behaviors (19%). Men in the Multiple Behaviors class had a
      67% probability of being STI positive, followed by men in the UAI Only class
      (27%) and men in the Partner Seekers class (22%). Examining the intersection of a
      variety of sexual practices indicates particular subgroups of MSM have the
      highest probability of being STI positive.

PMID- 27712109
TI  - Assessing Stress-Induced Sleep Reactivity in College Students: The European
      Portuguese Version of the Ford Insomnia Response to Stress Test (FIRST).
AB  - OBJECTIVE AND BACKGROUND: Over the past few years, the comprehensive models of
      insomnia have exhibited impressive developments. However, there is scarce
      knowledge on predisposing or vulnerability factors for insomnia. One of the most
      promising constructs to aid in filling this gap is stress-induced sleep
      reactivity assessed through self-report. Our aim was to study the psychometric
      properties of the European Portuguese version of the Ford Insomnia Response to
      Stress Test (FIRST). PARTICIPANTS: We recruited a large sample of students
      attending medical school (N = 699). METHODS: Several analyses were carried out
      such as internal consistency, construct validity, and discriminant groups'
      analysis. RESULTS: It was observed that FIRST-PT shows good internal consistency
      (Cronbach's alpha = .81) and validity indicators. Interestingly, and contrary to
      what was observed in the previously published studies on psychometric properties
      of the FIRST, it was observed that a two-factor solution (Factor I = rumination,
      Factor II = worry) was the most adequate one to explain the correlation matrix,
      accounting for approximately 44% of the total variance. CONCLUSIONS: The FIRST-PT
      proved to be a useful and reliable tool to measure stress-induced sleep
      reactivity. However, these results should be replicated in other groups,
      particularly clinical samples, in order to verify the stability of its factorial
      dimension.

PMID- 27712110
TI  - CADASIL and multiple sclerosis: A case report of prolonged misdiagnosis.
AB  - CADASIL is Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy [corrected]. (CADASIL) is sometimes misdiagnosed as multiple
      sclerosis (MS). MS and CADASIL are not known to co-occur and brain magnetic
      resonance imagining (MRI) findings can help with differential diagnosis. Despite
      the availability of this information, a case report is presented of a 61-year-old
      woman who was misdiagnosed with MS at age 50, tested positive for CADASIL at age
      56, described incorrectly as having both conditions simultaneously, and continued
      on MS disease-modifying medications, resulting in financial and physical
      hardship. Neuropsychological consultation helped initiate removal of the MS
      diagnosis and treatment. Better understanding is needed among clinicians that MS
      and CADASIL are not known to co-exist, that no association has been found between
      MS and the NOTCH3 mutations that cause CADASIL, and that neuroimaging and
      clinical features can help distinguish between the two conditions in addition to
      genetic testing. This case study highlights how neuropsychological consultation
      involves more than testing, can help improve diagnostic decision making, and can
      improve outcomes by reducing costs to the patient and the healthcare system.

PMID- 27712111
TI  - Mastery, Isolation, or Acceptance: Gay and Bisexual Men's Construction of Aging
      in the Context of Sexual Embodiment After Prostate Cancer.
AB  - Age is the predominant risk factor for developing prostate cancer, leading to its
      description as an "older man's disease." Changed sexual embodiment is a concern
      for men who develop prostate cancer, often compounding experiences of age-related
      sexual decline. Although research has examined heterosexual men's experiences of
      aging in the context of sexual embodiment after prostate cancer, gay and bisexual
      men have received little attention. This qualitative study used a material
      discursive analysis, drawing on positioning theory and intersectionality, to
      explore constructions of aging following prostate cancer in 46 gay or bisexual
      men. Thematic decomposition of one-to-one interviews identified three subject
      positions: "mastering youth," involving maintaining an active sex life through
      biomedical interventions, accessing commercial sex venues, or having sex with
      younger men; "the lonely old recluse," involving self-positioning as prematurely
      aged and withdrawal from a gay sexual scene; and "accepting embodied aging,"
      involving the incorporation of changed sexual function into intimate
      relationships and finding pleasure through nonsexual activities. These subject
      positions are conceptualized as the product of intersecting masculine and gay
      identities, interpreted in relation to broader cultural discourses of "new aging"
      and "sexual health," in which sexual activity is conceptualized as a lifelong
      goal.

PMID- 27712112
TI  - Attentional bias toward alcohol-related stimuli in heavy drinkers: evidence from
      dynamic eye movement recording.
AB  - BACKGROUND: It has been proposed that attentional biases toward alcohol stimuli
      are contributing factors maintaining problematic drinking behavior. OBJECTIVE:
      The main goal of the present set of studies was to provide an examination of
      dynamic attentional mechanisms associated with alcohol consumption derived from
      eye movement monitoring. METHOD: Undergraduate students were recruited for two
      studies. In Experiment 1, 80 students were exposed to complex scenes (containing
      alcohol-related cues or not) viewed at a self-determined presentation rate. In
      Experiment 2, 80 students were exposed to the stimuli for a fixed presentation
      time and asked to memorize the photographs. In both studies, participants
      completed the Khavari Alcohol Test (KAT) to measure their drinking behaviors.
      RESULTS: Experiment 1 revealed that alcohol consumption was unrelated to eye
      movement measures on alcohol-related objects within pictures. However, results of
      Experiment 2 indicated that saccades into and out of the alcohol-related zones
      were more frequent as alcohol consumption increased. The time spent and the speed
      of the first fixation in the alcohol-related zone did not explain the variance in
      alcohol consumption. CONCLUSION: Attentional biases associated with alcohol
      consumption might be better understood in terms of dynamic attention mechanisms.
      More precisely, heavy drinker's attention seems to be constantly drawn back to
      alcohol-related objects once they are first fixated and when attention is
      enforced through other cognitive demands. From a clinical viewpoint, dynamic
      attentional biases might contribute to the development or maintenance of alcohol
      related problems and this observation might help guide attention-based
      interventions.

PMID- 27712114
TI  - Hidden Markov Item Response Theory Models for Responses and Response Times.
AB  - Current approaches to model responses and response times to psychometric tests
      solely focus on between-subject differences in speed and ability. Within
      subjects, speed and ability are assumed to be constants. Violations of this
      assumption are generally absorbed in the residual of the model. As a result,
      within-subject departures from the between-subject speed and ability level remain
      undetected. These departures may be of interest to the researcher as they reflect
      differences in the response processes adopted on the items of a test. In this
      article, we propose a dynamic approach for responses and response times based on
      hidden Markov modeling to account for within-subject differences in responses and
      response times. A simulation study is conducted to demonstrate acceptable
      parameter recovery and acceptable performance of various fit indices in
      distinguishing between different models. In addition, both a confirmatory and an
      exploratory application are presented to demonstrate the practical value of the
      modeling approach.

PMID- 27712113
TI  - Palonosetron and hydroxyzine pre-treatment reduces the objective signs of
      experimentally-induced acute opioid withdrawal in humans: a double-blinded,
      randomized, placebo-controlled crossover study.
AB  - BACKGROUND: Treatments for reducing opioid withdrawal are limited and prone to
      problematic side effects. Laboratory studies, clinical observations, and limited
      human trial data suggest 5-HT3-receptor antagonists and antihistamines may be
      effective. OBJECTIVES: This double-blind, crossover, placebo-controlled study
      employing an acute physical dependence model evaluated whether (i) treatment with
      a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal
      symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would
      enhance any treatment effect. METHODS: At timepoint T = 0, healthy (non-opioid
      dependent, non-substance abuser) male volunteers (N = 10) were pre-treated with
      either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg)
      and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T =
      30 by intravenous morphine (10 mg/70kg). At T = 165, 10 mg/70kg naloxone IV was
      given to precipitate opioid withdrawal. The objective opioid withdrawal score
      (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15
      minutes after naloxone administration (T = 170, 180, respectively). Baseline
      measurements were recorded at T = -30 and T = -15. RESULTS: Comparison of average
      baseline OOWS scores with OOWS scores obtained 15 minutes after naloxone was
      significant (p = 0.0001). Scores from 15 minutes post-naloxone infusion showed
      significant differences in OOWS scores between treatment groups: placebo, 3.7 +/-
      2.4; palonosetron, 1.5 +/- 0.97; and palonosetron with hydroxyzine, 0.2 +/-
      0.1333. CONCLUSIONS: Pretreatment with palonosetron significantly reduced many
      signs of experimentally-induced opioid withdrawal. Co-administration with
      hydroxyzine further reduced opioid withdrawal severity. These results suggest
      that 5-HT3 receptor antagonists, alone or in combination with an antihistamine,
      may be useful in the treatment of opioid withdrawal.

PMID- 27712115
TI  - An exploration of pain-related vocabulary: implications for AAC use with
      children.
AB  - Children with significant communication difficulties who experience pain need
      appropriate means to communicate their pain in order to receive appropriate
      treatment. Augmentative and alternative communication (AAC) strategies could be
      used to enable children to self-report pain. The aim of this research study was
      to identify the common vocabulary children with typical development use to
      describe physical pain experiences and develop and socially validate an
      appropriate pain-related vocabulary list for children who use or could benefit
      from using AAC. A sequential, exploratory, mixed-method design was employed. This
      paper focuses on the quantitative phase. A set of scenarios was developed to
      gather pain-related vocabulary appropriate for children aged 6;0-7;11
      (years;months) and children aged 8;0-9;11, from 74 children, 61 parents, and 56
      teachers. Some 629 pain-related words or phrases were suggested and then
      classified into seven categories. A composite list of the 84 most frequently
      occurring pain-related vocabulary items was compiled and socially validated by
      three adults who used AAC. They emphasized the need to individualize vocabulary
      and provided suggestions for vocabulary organization for display on any type of
      AAC system. Despite similarities in the categories of words offered by the
      various respondent groups, the differences underscore the importance of more than
      one perspective (particularly that of children and adults) in generating a
      comprehensive vocabulary list.

PMID- 27712116
TI  - Estimation of the Coefficient of Variation with Minimum Risk: A Sequential Method
      for Minimizing Sampling Error and Study Cost.
AB  - The coefficient of variation is an effect size measure with many potential uses
      in psychology and related disciplines. We propose a general theory for a
      sequential estimation of the population coefficient of variation that considers
      both the sampling error and the study cost, importantly without specific
      distributional assumptions. Fixed sample size planning methods, commonly used in
      psychology and related fields, cannot simultaneously minimize both the sampling
      error and the study cost. The sequential procedure we develop is the first
      sequential sampling procedure developed for estimating the coefficient of
      variation. We first present a method of planning a pilot sample size after the
      research goals are specified by the researcher. Then, after collecting a sample
      size as large as the estimated pilot sample size, a check is performed to assess
      whether the conditions necessary to stop the data collection have been satisfied.
      If not an additional observation is collected and the check is performed again.
      This process continues, sequentially, until a stopping rule involving a risk
      function is satisfied. Our method ensures that the sampling error and the study
      costs are considered simultaneously so that the cost is not higher than necessary
      for the tolerable sampling error. We also demonstrate a variety of properties of
      the distribution of the final sample size for five different distributions under
      a variety of conditions with a Monte Carlo simulation study. In addition, we
      provide freely available functions via the MBESS package in R to implement the
      methods discussed.

PMID- 27712118
TI  - Zika virus epidemic: an update.
AB  - INTRODUCTION: Zika Virus (ZIKV), previously the cause of only rare and sporadic
      human infections, is now considered a Public Health Emergency of International
      Concern. Over the past two years, ZIKV has become a pandemic encompassing much of
      the Americas. ZIKV is now proven to cause microcephaly and ophthalmic anomalies
      in the newborn. Hydrops fetalis, developmental delay, and other anomalies are
      increasingly being attributed to ZIKV infection in fetuses and neonates. Sequelae
      of congenital infection and rapid spread of ZIKV throughout the Americas has
      catapulted Zika virus concerns to the forefront of the medical community. Areas
      covered: This review seeks to consolidate ZIKV epidemiology, diagnostic testing
      methods, CDC screening recommendations, and preventive strategies including
      potential vaccines. Expert commentary: Many unknowns still exist regarding ZIKV
      infections and its long-term effects in neonates. In addition, further studies
      need to evaluate if genomic differences that have occurred from the African to
      the Asian lineage of the virus have led to increased virulence of the virus. The
      authors believe that all pregnant women with fetuses showing microcephaly and/or
      intracranial calcifications should be tested for ZIKV infection if they cannot
      recall their sexual partner travel history. This change from the current CDCs
      recommendations could increase substantially the number of pregnant women and
      neonates, screened for ZIKV.

PMID- 27712120
TI  - Craving, prayer, and the brain.

PMID- 27712117
TI  - Clinical relevance of midline fluid percussion brain injury: Acute deficits,
      chronic morbidities and the utility of biomarkers.
AB  - BACKGROUND: After 30 years of characterisation and implementation, fluid
      percussion injury (FPI) is firmly recognised as one of the best-characterised
      reproducible and clinically relevant models of TBI, encompassing concussion
      through diffuse axonal injury (DAI). Depending on the specific injury parameters
      (e.g. injury site, mechanical force), FPI can model diffuse TBI with or without a
      focal component and may be designated as mild-to-severe according to the chosen
      mechanical forces and resulting acute neurological responses. Among FPI models,
      midline FPI may best represent clinical diffuse TBI, because of the acute
      behavioural deficits, the transition to late-onset behavioural morbidities and
      the absence of gross histopathology. REVIEW: The goal here was to review acute
      and chronic physiological and behavioural deficits and morbidities associated
      with diffuse TBI induced by midline FPI. In the absence of neurodegenerative
      sequelae associated with focal injury, there is a need for biomarkers in the
      diagnostic, prognostic, predictive and therapeutic approaches to evaluate
      outcomes from TBI. CONCLUSIONS: The current literature suggests that midline FPI
      offers a clinically-relevant, validated model of diffuse TBI to investigators
      wishing to evaluate novel therapeutic strategies in the treatment of TBI and the
      utility of biomarkers in the delivery of healthcare to patients with brain
      injury.

PMID- 27712119
TI  - Identification of problems in the functioning of individuals with schizophrenia
      from the expert perspective: an Internet-based survey.
AB  - PURPOSE: The purpose of the study was to identify aspects of functioning and
      related environmental factors that are relevant to schizophrenia from the
      perspective of health professionals experienced in treating individuals with this
      disorder using the International Classification of Functioning, Disability and
      Health (ICF). METHOD: An international pool of experts from diverse health care
      disciplines was surveyed to identify problems in functioning experienced by
      individuals with schizophrenia and the environmental factors that impact their
      functioning. On the basis of established rules, all answers were translated to
      the ICF by two independent researchers. RESULTS: One-hundred and eighty-nine
      experts from all six World Health Organization regions identified 4776 meaningful
      concepts, of which 92% were linked to 347 different ICF categories. Of the 347
      categories, 194 were second-level categories, 151 were third-level categories and
      2 were fourth-level categories. Ninety-five second-level ICF categories, 43 third
      level categories and 1 fourth-level category reached percentage frequency of at
      least 5%. The majority of the categories were attributed to body functions,
      activities and participation, and environmental factors. CONCLUSIONS: Health
      professionals identified a wide range of problems in functioning that reflect the
      complexity and breadth of schizophrenia, specifically activity limitations and
      participation restrictions that are particularly relevant for individuals with
      schizophrenia. Knowing these functioning problems can guide the design of patient
      oriented rehabilitation programmes. Implications for rehabilitation Schizophrenia
      may result in impaired functioning in multiple daily life activities. The
      International Classification of Functioning, Disability and Health (ICF) can help
      in identifying the needs and problems of these individuals. The reported list of
      ICF categories can facilitate a systematic application of the ICF in
      schizophrenia and can help to design and implement coordinated and patient
      oriented rehabilitation programmes with a biopsychosocial approach. According to
      health professionals surveyed, activity limitations and participation
      restrictions are broadly affected in this population and are highly influenced by
      neurocognitive and social cognitive deficits and environmental factors.

PMID- 27712121
TI  - The importance of building trust and tailoring interactions when meeting older
      adults' health literacy needs.
AB  - PURPOSE: Health literacy is the ability to access, understand and use health
      information. This study qualitatively explored the views and experiences of older
      adults with varying health literacy levels who had attended a falls clinic on
      their overall experience of the falls clinic, access to the service and provider
      patient interaction. METHODS: Individual semi-structured interviews were
      conducted with nine older adults using a falls clinic in England. Health literacy
      was assessed using the REALM and NVS-UK. Interviews were audio-recorded,
      transcribed verbatim and interrogated using interpretative phenomenological
      analysis (IPA). RESULTS: Two superordinate themes emerged from the analysis: The
      importance of trust and relationship building to achieve effective communication
      with older adults; and the importance of tailoring education and healthcare to
      older adults' individual health literacy needs and preferences. CONCLUSIONS: The
      findings corroborate previous research emphasising the importance of face-to-face
      communication in responding to older adults' individual health literacy needs.
      Building trust in the relationship and tailoring communication to older adults'
      individual attributes and preferred learning styles is essential. Healthcare
      practitioners and managers should consider how service organisation and
      communication methods can enhance positive and effective relationships with
      patients. Improved training could support healthcare providers in meeting
      patients' personal communication needs. Implications for Rehabilitation
      Rehabilitation professionals should be aware of their patients' individual health
      literacy needs and communication/learning preferences. It is important to build
      relationships and trust with older adults attending rehabilitation services.
      Further training for rehabilitation professionals could support them in meeting
      patients' personal communication needs.

PMID- 27712122
TI  - The relationship between circulating visfatin/nicotinamide
      phosphoribosyltransferase, obesity, inflammation and lipids profile in elderly
      population, determined by structural equation modeling.
AB  - BACKGROUND: The available literature suggests that circulating
      visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) level variability in
      humans is related to obesity, insulin resistance, inflammation, and lipid
      profile. The aim of the study was to assess the relationship between circulating
      visfatin/NAMPT, obesity, insulin resistance, inflammation, and lipid profile in a
      large population-based, elderly cohort, applying structural equation modeling.
      MATERIALS AND METHODS: The analysis included 2983 elderly participants of the
      PolSenior study with assessed total blood count, fasting concentrations of
      lipids, glucose, insulin, hs-CRP, interleukin-6, and visfatin/NAMPT (by ELISA),
      and calculated HOMA-IR. RESULTS: The circulating visfatin/NAMPT levels were
      higher in obese compared to normal weight subjects, in those with hs-CRP above 3
      mg/L, with low serum HDL cholesterol, and in insulin resistant subjects. Based on
      results of the exploratory factor analysis, a baseline model of mutual
      relationship between four latent and measured variables was created and a final
      model was developed by maintaining only two significant categories. The important
      variables for 'latent inflammation' proved to be hs-CRP and IL-6 serum levels. In
      the case of 'nutritional status', important variables were BMI, waist
      circumference, and to a lesser extent insulin resistance. Additionally, the
      residual correlation between those two constructs was also statistically
      significant. CONCLUSION: The structural equation modeling provided support for
      the existence of a link between nutritional status, inflammation and circulating
      visfatin/NAMPT level. This indicates that circulating visfatin/NAMPT can be
      considered as a novel surrogate marker of systemic inflammation associated with
      fat depot, especially visceral, in the elderly population.

PMID- 27712123
TI  - Intervening to address communication difficulties in incarcerated youth: A Phase
      1 clinical trial.
AB  - PURPOSE: Although a number of studies have described high rates of wide-ranging
      language difficulties in youth offender samples, minimal intervention research
      has been conducted with this population. The aim of this study was to implement a
      small-scale speech-language pathology (SLP) intervention study in a secure youth
      justice facility and to identify key practical challenges associated with
      conducting SLP interventions in youth custodial settings. METHOD: Six young males
      were recruited and underwent assessment via a range of standardised and self
      report communication measures. Measures of nonverbal IQ and of therapeutic
      engagement were also employed, and participants' own goals concerning
      communication competence were incorporated into treatment. Participants completed
      seven to 16 weeks' of 1:1 SLP intervention, once or twice per week. RESULT:
      Therapeutic engagement was generally strong. All participants made gains and
      responded favourably regarding the usefulness of the intervention. Many practical
      issues conspired to make this a challenging SLP intervention setting. CONCLUSION:
      Youth custodial sentences represent an important opportunity for high-risk youths
      with compromised communication skills to receive specialist SLP therapeutic
      services to reduce the impact of their communication difficulties post-release
      into the community.

PMID- 27712125
TI  - The impact of childhood language difficulties on healthcare costs from 4 to 13
      years: Australian longitudinal study.
AB  - PURPOSE: This study investigated the relationship between children's language
      difficulties and health care costs using the 2004-2012 Longitudinal Study of
      Australian Children (LSAC). METHOD: Language difficulties were defined as scores
      <=1.25SD below the standardised mean on measures of directly assessed receptive
      vocabulary (4-9 years) and teacher-reported language and literacy (10-13 years).
      Participant data were individually linked to administrative data, which were
      sourced from Australia's universal subsidised healthcare scheme (Medicare).
      RESULT: It was found that healthcare costs over each 2-year age band were higher
      for children with language difficulties than without in the 4-5-year-age bracket
      (mean difference = AU$357, 95%CI $59, $659), in the 6-7-year-age bracket (mean
      difference = AU$602, 95%CI $136, $1068) and in the 10-11-year-age bracket (mean
      difference = AU$504, 95%CI $153, $854). Out-of-pocket costs, that is the portion
      of healthcare costs paid for by the family, were also higher for children with
      than without language difficulties in the 4-5-year-age bracket (mean difference =
      AU$123, 95%CI $46, $199), in the 6-7-year-age bracket (mean difference = AU$176,
      95%CI $74,278) and in the 10-11-year-age bracket (mean difference = AU$79, 95%CI
      $6, $152). Medical services accounted for 97% of total healthcare cost
      differences. CONCLUSION: Overall the findings from this study suggest that
      language difficulties are associated with increased healthcare costs at key
      developmental milestones, notably early childhood and as a child approaches the
      teenage years.

PMID- 27712126
TI  - Perceptions of e-cigarettes: a comparison of adult smokers and non-smokers in a
      Mechanical Turk sample.
AB  - BACKGROUND: Given plans to extend its regulatory authority to e-cigarettes, the
      Food and Drug Administration (FDA) urgently needs to understand how e-cigarettes
      are perceived by the public. OBJECTIVES: To examine how smoking status impacts
      adult perceptions and expectations of e-cigarettes. METHODS: We used Mechanical
      Turk (MTurk), a "crowdsourcing" platform, to rapidly survey a large (n = 796;
      female = 381; male = 415), diverse sample of adult ever (44%) and never smokers
      (56%), including ever (28%) and never (72%) users of e-cigarettes. RESULTS:
      Smokers and non-smokers learned about e-cigarettes primarily through the internet
      and conversations with others. Ever smokers were more likely than never smokers,
      and female current smokers were more likely than female former smokers, to have
      learned about e-cigarettes from point of sale advertising (p's < 0.05) and to
      believe that e-cigarettes help smokers quit (ps < 0.05). Among never users of e
      cigarettes, current smokers were more likely than never smokers and former
      smokers to report that they would try e-cigarettes in the future (ps < 0.01).
      Current smokers' top reason for wanting to try e-cigarettes was to quit or reduce
      smoking (56%), while never and former smokers listed curiosity. In contrast,
      female current smokers' top reason for not trying e-cigarettes was health and
      safety concerns (44%) while males were deterred by expense (44%). CONCLUSIONS:
      Adult smokers and non-smokers have different perceptions and expectations of e
      cigarettes. Public health messages regarding e-cigarettes may need to be tailored
      separately for persons with and without a history of using conventional
      cigarettes. Tailoring messages by gender within smoker groups may also improve
      their impact.

PMID- 27712127
TI  - Quantifying pupillary asymmetry through objective binocular pupillometry in the
      normal and mild traumatic brain injury (mTBI) populations.
AB  - INTRODUCTION: Little is known about human inter-ocular pupillary asymmetry
      (IOPA). Thus, the purpose of the present investigation was to assess objectively
      static and dynamic IOPA in normals and in individuals with mild traumatic brain
      injury (mTBI). METHODS: The pupillary light reflex (PLR) was assessed in an adult
      population of normals and in those with mTBI using the Neuroptics DP-2000
      binocular pupillometer. Four stimulus conditions were used to optimize the
      assessment. Two aspects of the pupil were assessed: baseline diameter prior to
      light stimulation and the dynamic amplitude of constriction following light
      stimulation. RESULTS: There was no statistical difference in either the static or
      dynamic IOPA between the two groups. Thus, the data were combined for a better
      global parameter estimate. The mean average static IOPA was 0.26 mm (SD = +/-
      0.20 mm) or 4.17% (+/- 3.29%). The mean average dynamic IOPA was dependent on the
      light stimulus condition, with the average across all four test conditions being
      0.11 mm (+/- 0.10 mm) or 1.84% (+/- 1.70%). DISCUSSION: The inter-ocular
      pupillary effects of mTBI appear to be symmetrical rather than asymmetrical in
      nature. The findings provide clinicians and researchers a useful quantitative
      guideline to assess normal vs abnormal static and dynamic inter-ocular pupillary
      asymmetry (IOPA) in these two populations.

PMID- 27712124
TI  - Leveraging allostery to improve G protein-coupled receptor (GPCR)-directed
      therapeutics: cannabinoid receptor 1 as discovery target.
AB  - INTRODUCTION: Allosteric modulators of G-protein coupled receptors (GPCRs) hold
      the promise of improved pharmacology and safety over typical orthosteric GPCR
      ligands. These features are particularly relevant to the cannabinoid receptor 1
      (CB1R) GPCR, since typical orthosteric CB1R ligands are associated with adverse
      events that limit their translational potential. Areas covered: The contextual
      basis for applying allostery to CB1R is considered from pharmacological, drug
      discovery, and medicinal standpoints. Rational design of small-molecule CB1R
      allosteric modulators as potential pharmacotherapeutics would be greatly
      facilitated by direct experimental characterization of structure-function
      correlates underlying the biological activity of chemically-diverse CB1R
      allosteric modulators, CB1R allosteric ligand-binding binding pockets, and amino
      acid contact residues critical to allosteric ligand engagement and activity. In
      these regards, designer covalent probes exhibiting well-characterized molecular
      pharmacology as CB1R allosteric modulators are emerging as valuable molecular
      reporters enabling experimental interrogation of CB1R allosteric site(s) and
      informing the design of new CB1R agents as drugs. Expert opinion: Synthesis and
      pharmacological profiling of CB1R allosteric ligands will continue to provide
      valuable insights into CB1R structure-function correlates. The resulting data
      should expand the repertoire of novel agents capable of exerting therapeutic
      benefit by modulating CB1R-dependent signaling.

PMID- 27712129
TI  - Corrigendum.

PMID- 27712128
TI  - Association between Q192R paraoxonase 1 polymorphism and serumadipocyte-fatty
      acid binding protein (FABP4) levels in Mexican women.
AB  - AIM: This study aimed to evaluate the genetic effects of PON1 Q192R polymorphism
      on serum FABP4 levels in Mexican women. METHODS: PON1 Q192R polymorphism was
      genotyped using a TaqMan allelic discrimination assay and serum FABP4
      concentration was measured using an enzyme-linked immunosorbent assay. RESULTS:
      The distribution of genotype frequencies in the assessed women (PON1 Q192R
      polymorphism) was QQ = 20%, QR = 48% and RR = 32%. Significantly higher serum
      FABP4 levels were found in women with genotype QR/RR (20.6 +/- 2.20 ng/mL), when
      compared with the levels found in the QQ group (12.8 +/- 1.70 ng/mL) (p = .004).
      After, the odds ratio (OR) was calculated by binomial logistic regression
      analysis and a significantly higher OR was found in the QR/RR group when compared
      with the QQ group (OR = 3.45; 95% CI = 1.80-16.50; p < .05). CONCLUSION: The
      results support an association between 192R-allele of the PON1 polymorphism
      (Q192R) and increased serum FABP4 levels (suggested as an early biomarker of CVDs
      risk) in assessed Mexican women.

PMID- 27712130
TI  - Serum levels of second-generation antipsychotics are associated with cognitive
      function in psychotic disorders.
AB  - OBJECTIVES: Antipsychotics are effective in treating psychosis and mood episodes;
      however, the effect on cognition is less known. We investigated the association
      between serum levels of second-generation antipsychotics (SGAs) and cognitive
      performance in psychosis spectrum disorders in a naturalistic setting. METHODS: A
      total of 495 patients with a DSM-IV Schizophrenia and Other Psychotic Disorders
      (SCZ, n = 373) or Bipolar Disorder (BD, n = 122) diagnosis treated with
      olanzapine, quetiapine, aripiprazole or risperidone were tested
      neuropsychologically with concurrent measurement of the serum concentration of
      the drug. Linear regression was used for association analyses. RESULTS: Attention
      was positively associated with the olanzapine concentration (standardised beta
      (beta) coefficient = 0.19, P = .006), and short-term verbal memory and verbal
      fluency were negatively associated with the quetiapine (beta = -0.24, P = .004)
      and risperidone (beta = -0.37, P = .007) concentrations respectively.
      CONCLUSIONS: The present results suggest that SGA serum concentration is
      associated with better attention (small effect size), and worse verbal memory
      (small effect size) and verbal fluency (medium effect size). These findings are
      in line with the notion that SGAs affect aspects of cognitive function, and
      suggest careful dosing in patients with severe memory and executive problems.

PMID- 27712131
TI  - Sudden sensorineural hearing loss: is there a relationship between routine
      haematological parameters and audiogram shapes?
AB  - OBJECTIVE: To investigate the relationship between haematological routine
      parameters and audiogram shapes in patients affected by sudden sensorineural
      hearing loss (SSNHL). DESIGN: A retrospective study. All patients were divided
      into four groups according to the audiometric curve and mean values of
      haematological parameters (haemoglobin, white blood cell, neutrophils and
      lymphocytes relative count, platelet count, haematocrit, prothrombin time,
      activated partial thromboplastin time, fibrinogen and neutrophil-to-lymphocite
      ratio) of each group were statistically compared. The prognostic role of blood
      profile and coagulation test was also examined. STUDY SAMPLE: A cohort of 183
      SSNHL patients without comorbidities. RESULTS: With a 48.78% of complete hearing
      recovery, individuals affected by upsloping hearing loss presented a better
      prognosis instead of flat (18.36%), downsloping (19.23%) and anacusis (2.45%)
      groups (p = 0.0001). The multivariate analysis of complete blood count values
      revealed lower mean percentage of lymphocytes (p = 0.041) and higher platelet
      levels (p = 0.015) in case of downsloping hearing loss; with the exception of
      fibrinogen (p = 0.041), none of the main haematological parameters studied
      resulted associated with poorer prognosis. CONCLUSIONS: Our work suggested a lack
      of association between haematological parameters and a defined audiometric
      picture in SSNHL patients; furthermore, only fibrinogen seems to influence the
      prognosis of this disease.

PMID- 27712132
TI  - Diagnostic utility of the HIV dementia scale and the international HIV dementia
      scale in screening for HIV-associated neurocognitive disorders among Spanish
      speaking adults.
AB  - Given that neurocognitive impairment is a frequent complication of HIV-1
      infection in Spanish-speaking adults, the limited number of studies assessing HIV
      associated neurocognitive disorders (HAND) in this population raises serious
      clinical concern. In addition to being appropriately translated, instruments need
      to be modified, normed, and validated accordingly. The purpose of the current
      study was to examine the diagnostic utility of the HIV Dementia Scale (HDS) and
      International HIV Dementia Scale (IHDS) to screen for HAND in Spanish-speaking
      adults living with HIV infection. Participants were classified as either HAND (N
      = 47) or No-HAND (N = 53) after completing a comprehensive neuropsychological
      evaluation. Receiver operating characteristic analyses found the HDS (AUC = .706)
      was more sensitive to detecting HAND than the IHDS (AUC = .600). Optimal cutoff
      scores were 9.5 for the HDS (PPV = 65.2%, NPV = 71.4%) and 9.0 for the IHDS (PPV
      = 59.4%, NPV = 59.1%). Canonical Correlation Analysis found the HDS converged
      with attention and executive functioning. Findings suggest that while the IHDS
      may not be an appropriate screening instrument with this population, the HDS
      retains sufficient statistical validity and clinical utility to screen for HAND
      in Spanish-speaking adults as a time-efficient and cost-effective measure in
      clinical settings with limited resources.

PMID- 27712133
TI  - EEG Derived Brain Activity Reflects Treatment Response from Vagus Nerve
      Stimulation in Patients with Epilepsy.
AB  - The mechanism of action of vagus nerve stimulation (VNS) is yet to be elucidated.
      To that end, the effects of VNS on the brain of epileptic patients were studied.
      Both when VNS was switched "On" and "Off", the brain activity of responders (R,
      seizure frequency reduction of over 50%) was compared to the brain activity of
      nonresponders (NR, seizure frequency reduction of less than 50%). Using EEG
      recordings, a significant increase in P300 amplitude for R and a significant
      decrease in P300 amplitude for NR were found. We found biomarkers for checking
      the efficacy of VNS with accuracy up to 94%. The results show that P300 features
      recorded in nonmidline electrodes are better P300 biomarkers for VNS efficacy
      than P300 features recorded in midline electrodes. Using source localization and
      connectivity analyses, the activity of the limbic system, insula and
      orbitofrontal cortex was found to be dependent on VNS switched "On" versus "Off"
      or patient group (R versus NR). The results suggest an important role for these
      areas in the mechanism of action of VNS, although a larger patient study should
      be done to confirm the findings.

PMID- 27712134
TI  - Dietary calcium intake is inversely associated with blood pressure in Brazilian
      children.
AB  - This study aimed to evaluate the dietary calcium intake and its association with
      blood pressure in childhood. It is a cross-sectional study with a sample of 347
      Brazilian children aged 8 and 9 years. We evaluated calcium intake through three
      dietary records. Blood pressure was measured following the recommendations of the
      Brazilian Society of Cardiology. The intake of calcium was below recommendations
      for almost all children (96.3%). There was statistically significant difference
      in the means of systolic (p = .041) and diastolic (p = .047) blood pressure in
      the tertiles of calcium intake. After adjustment of regression model, each
      tertile of calcium intake showed that the systolic and diastolic blood pressure
      was reduced in 1.53 (95% confidence interval: -2.84 to -0.21) and 1.83 mmHg (95%
      confidence interval: -3.49 to -0.19), respectively. Our results showed an inverse
      association between dietary calcium intake and blood pressure in childhood.

PMID- 27712135
TI  - Functional assessment of autologous platelet-rich plasma (PRP) after long-term
      storage at -20  degrees C without any preservation agent.
AB  - BACKGROUND: Platelet-rich plasma (PRP) is increasingly being used in the
      treatment of chronic wounds, pathologies of the musculoskeletal system, and in
      cosmetic medicine; however, the preparation of platelet-rich plasma is both time
      consuming and requires invasive intervention. Additional costs are introduced if
      special equipment is used during preparation. The aim of the present study is to
      test whether autologous platelet-rich plasma (PRP) preserves the feature of
      growth factor release when stored at -20  degrees C after preparation. METHOD:
      Autologous PRP concentrates were prepared using whole blood samples obtained from
      20 healthy subjects and divided into three parts to form three groups. Epidermal
      growth factor (EGF), vascular endothelial growth factor (VEGF), platelet derived
      growth factor-AB (PDGF-AB), insulin-like growth factor 1 (IGF-1), transforming
      growth factor-beta (TGF-beta), and P-Selectin levels were immediately analysed in
      the control group. The other groups were defined as the experimental groups and
      were stored at -20  degrees C and analysed on the 7th and the 14th days. The same
      growth factors were tested in the experimental groups. RESULTS: The growth
      factors (EGF, VEGF, PDGF-AB, IGF-1, TGF-beta) and P-selectin levels were
      significantly decreased in the autologous PRP samples stored at -20  degrees C
      compared to the control group. CONCLUSION: The growth factor levels on days 7 and
      14 suggest that autologous PRP can be stored at -20  degrees C without
      preservative agents, although in vivo studies are required in order to evaluate
      the clinical efficacy of the detected growth factor levels.

PMID- 27712136
TI  - Association between the variability of the ABCA13 gene and the risk of major
      depressive disorder and schizophrenia in the Han Chinese population.
AB  - OBJECTIVES: The ATP-binding cassette transporter superfamily is one of the
      largest membrane protein families, which is responsible for transportation of
      substances across the membranes by utilising energy. Some research has bridged
      the variations in ABCA13 with occurrence of psychiatric disorders. To investigate
      the overlapping risk conferred by ABCA13 for both major depressive disorder and
      schizophrenia, we analysed tag single nucleotide polymorphisms (tag SNPs).
      METHODS: We used TaqMan(r) technology to genotype 1045 major depressive disorder
      patients, 1235 schizophrenia patients and 1235 healthy controls of Han Chinese
      origin. RESULTS: We found that rs7789493 (Pallele = 7.23E-04, Pgenotype =.001)
      was associated with major depressive disorder, while rs17132388 (Pallele = 1.63E
      04, Pgenotype = 7.50E-04) and rs6583476 (Pallele = 5.50E-04, Pgenotype =.002)
      showed statistically significant association with schizophrenia. CONCLUSIONS: Our
      results indicate that the ABCA13 gene may contain overlapping common genetic risk
      factors for both major depressive disorder and schizophrenia in the Han Chinese
      population. The study on variants conferring overlapping risk for multiple
      psychiatric disorders could be tangible pathogenesis support in clinical or
      diagnostic references.

PMID- 27712139
TI  - Louise Crosby.
AB  - What gets you out of bed in the morning? I have been in post for only ten months
      so my current job still feels challenging and I'm still busy. I never feel there
      are enough hours in the day, but I think that's the same for most people in the
      NHS. Most days present tasks or elements of negotiation that I still find
      difficult, but which are rewarding once achieved.

PMID- 27712138
TI  - The ward managers' premier league.
AB  - FOR SOME TIME NOW, effective teamwork has been considered essential to the
      delivery of high quality health care ( Major2002 , Ryan1994 , Webster2002 ), with
      team nursing commonly reflected in ward philosophies.

PMID- 27712137
TI  - An update on the management of urinary tract infections in the era of
      antimicrobial resistance.
AB  - Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-negative
      bacteria are a growing concern due to limited therapeutic options. Gram-negative
      bacteria, specifically Enterobacteriaceae, are common causes of both community
      acquired and hospital acquired UTIs. These organisms can acquire genes that
      encode for multiple antibiotic resistance mechanisms, including extended-spectrum
      lactamases (ESBLs), AmpC- beta -lactamase, and carbapenemases. The assessment of
      suspected UTI includes identification of characteristic symptoms or signs,
      urinalysis, dipstick or microscopic tests, and urine culture if indicated. UTIs
      are categorized according to location (upper versus lower urinary tract) and
      severity (uncomplicated versus complicated). Increasing rates of antibiotic
      resistance necessitate judicious use of antibiotics through the application of
      antimicrobial stewardship principles. Knowledge of the common causative pathogens
      of UTIs including local susceptibility patterns are essential in determining
      appropriate empiric therapy. The recommended first-line empiric therapies for
      acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant
      females is a 5-day course of nitrofurantion or a 3-g single dose of fosfomycin
      tromethamine. Second-line options include fluoroquinolones and beta-lactams, such
      as amoxicillin-clavulanate. Current treatment options for UTIs due to AmpC- beta 
      lactamase-producing organisms include fosfomycin, nitrofurantion,
      fluoroquinolones, cefepime, piperacillin-tazobactam and carbapenems. In addition,
      treatment options for UTIs due to ESBLs-producing Enterobacteriaceae include
      nitrofurantion, fosfomycin, fluoroquinolones, cefoxitin, piperacillin-tazobactam,
      carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides.
      Based on identification and susceptibility results, alternatives to carbapenems
      may be used to treat mild-moderate UTIs caused by ESBL-producing
      Enterobacteriaceae. Ceftazidime-avibactam, colistin, polymixin B, fosfomycin,
      aztreonam, aminoglycosides, and tigecycline are treatment options for UTIs caused
      by carbapenem-resistant Enterobacteriaceae (CRE). Treatment options for UTIs
      caused by multidrug resistant (MDR)-Pseudomonas spp. include fluoroquinolones,
      ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides,
      colistin, ceftazidime-avibactam, and ceftolozane-tazobactam. The use of
      fluoroquinolones for empiric treatment of UTIs should be restricted due to
      increased rates of resistance. Aminoglycosides, colistin, and tigecycline are
      considered alternatives in the setting of MDR Gram-negative infections in
      patients with limited therapeutic options.

PMID- 27712140
TI  - Worth the investment.
AB  - DEVELOPING LEADERS at all levels is central to the modernisation of the NHS. But
      sustaining the level of investment needed for leadership development can pose
      challenges for trusts, which lead many to question whether such investment
      genuinely improves the quality and delivery of patient care.

PMID- 27712141
TI  - Expression and methylation of BDNF in the human brain in schizophrenia.
AB  - OBJECTIVES: To examine the combined effect of the BDNF Val66Met (rs6265)
      polymorphism and BDNF DNA methylation on transcriptional regulation of the BDNF
      gene. METHODS: DNA methylation profiles were generated for CpG sites proximal to
      Val66Met, within BDNF promoter I and exon V for prefrontal cortex samples from 25
      schizophrenia and 25 control subjects. Val66Met genotypes and BDNF mRNA
      expression data were generated by transcriptome sequencing. Expression,
      methylation and genotype data were correlated and examined for association with
      schizophrenia. RESULTS: There was 43% more of the BDNF V-VIII-IX transcript in
      schizophrenia samples. BDNF mRNA expression and DNA methylation of seven CpG
      sites were not associated with schizophrenia after accounting for age and PMI
      effects. BDNF mRNA expression and DNA methylation were not altered by Val66Met
      after accounting for age and PMI effects. DNA methylation of one CpG site had a
      marginally significant positive correlation with mRNA expression in schizophrenia
      subjects. CONCLUSIONS: Schizophrenia risk was not associated with differential
      BDNF mRNA expression and DNA methylation. A larger age-matched cohort with
      comprehensive clinical history is required to accurately identify the effects of
      genotype, mRNA expression and DNA methylation on schizophrenia risk.

PMID- 27712142
TI  - Chronic obstructive airway disease among patients hospitalized with acute heart
      failure; clinical characteristics, precipitating factors, management and outcome:
      Observational report from the Middle East.
AB  - BACKGROUND: The purpose of this study was to report the prevalence, clinical
      characteristics, contributing factors, management and outcome of patients with
      chronic obstructive pulmonary disease (COPD) among patients hospitalized with
      heart failure (HF). METHODS: Data were derived from Gulf Care (Gulf acute heart
      failure registry), a prospective multicenter study of 5005 consecutive patients
      hospitalized with acute heart failure during February to November 2012 in seven
      Middle Eastern countries. Data were described and compared for demographics,
      management and outcomes. RESULTS: The prevalence of COPD among HF patients was
      10%. COPD patients were older, more likely to be female and to have diabetes,
      hypertension, chronic kidney disease and sleep apnea (P = 0.001 for all) when
      compared to non-COPD patients. Contributing factors for hospitalization were
      systemic infection and atrial arrhythmias in COPD patients compared to acute
      coronary syndrome, uncontrolled hypertension and anemia in the non-COPD patients.
      Left-ventricular ejection fraction was higher in COPD patients; while BNP levels
      were comparable between the two groups. Non-invasive ventilation was used more
      frequently among COPD patients compared to non-COPD patients (P = 0.001). On
      multivariate logistic regression analysis, COPD was not associated with increased
      risk in-hospital and one-year death among acute heart failure (AHF) population
      and beta blockers treatment appear to have neutral mortality effect in COPD
      patients with HF. CONCLUSION: COPD have distinct cardiovascular risk profile and
      precipitating factors for hospitalization with HF when compared to non-COPD
      patients. COPD history had no impact on the short-term and one-year mortality.

PMID- 27712143
TI  - Mayo registry for telemetry efficacy in arrest (MR TEA) study: An assessment of
      the effect of admission diagnosis on outcomes from in-hospital cardiopulmonary
      arrest.
AB  - INTRODUCTION: Little data exists evaluating how different risk factors influence
      outcomes following in-hospital arrests. METHODS: A retrospective review of
      patients that suffered a cardiopulmonary arrest between 1 May 2008 and 30 June
      2014 was performed. Patients were stratified into subsets based on cardiac versus
      non-cardiac reasons for admission. RESULTS: 199 patients met inclusion criteria,
      of which 138 (69.3%) had a non-cardiac reason for admission and 61 (30.7%) a
      cardiac etiology. No difference in demographics and non-cardiac comorbidities
      were present. Cardiac-related comorbidities were more prevalent in the cardiac
      etiology subset. Arrests with a shockable rhythm were more common in the cardiac
      group (P < 0.0001), yet return of spontaneous circulation from the index event
      was similar (P = 0.254). More patients in the cardiac group were alive at 24-h
      post resuscitation (n = 34, 55.7% versus n = 49, 35.5%; P = 0.0085), discharge (n
      = 21, 34.4% versus n = 19, 13.8%; P = 0.0018), and at last follow-up (n = 13,
      21.3% versus n = 14, 10.1%; P = 0.0434). CONCLUSION: Although patients with
      cardiac and non-cardiac etiologies for admission have similar rates of return of
      spontaneous circulation, those with cardiac etiologies are more likely to survive
      to hospital discharge and outpatient follow-up.

PMID- 27712145
TI  - Face to face.
AB  - I was inspired to work with older people by a ward sister during my training. She
      was a fantastic role model who showed me that working with older people covers
      every facet of nursing, from managing multiple conditions and polypharmacy, to
      rehabilitation and palliative care.

PMID- 27712146
TI  - Make the strategy a reality.
AB  - The National Dementia Strategy was published in February 2009 with the intention
      that dementia would be a national priority. Yet a year on, services for people
      with dementia still do not provide value for money. This is the unsatisfactory
      conclusion of the National Audit Office ( 2010 ) report into implementation of
      the strategy ( page 8 ). The Department of Health is criticised, with a call for
      stronger leadership and joined up working between health and social care services
      for people with dementia.

PMID- 27712147
TI  - Alcohol Is alcohol misuse only a problem in the younger generation?
AB  - The popular image of older people requesting a small sherry with their Christmas
      lunch and becoming tipsy is an erroneous view of their drinking habits. People do
      not stop drinking hazardously simply because they are older. Bereavement,
      isolation and pain are a potent mix when combined with the low cost and
      accessibility of alcohol. It is likely therefore that there will be an increase
      in the need for alcohol services for older people.

PMID- 27712144
TI  - Regulation of fixLJ by Hfq Controls Symbiotically Important Genes in
      Sinorhizobium meliloti.
AB  - The RNA-binding chaperone Hfq plays critical roles in the establishment and
      functionality of the symbiosis between Sinorhizobium meliloti and its legume
      hosts. A mutation in hfq reduces symbiotic efficiency resulting in a Fix-
      phenotype, characterized by the inability of the bacterium to fix nitrogen. At
      least in part, this is due to the ability of Hfq to regulate the fixLJ operon,
      which encodes a sensor kinase-response regulator pair that controls expression of
      the nitrogenase genes. The ability of Hfq to bind fixLJ in vitro and in planta
      was demonstrated with gel shift and coimmunoprecipitation experiments. Two (ARN)2
      motifs in the fixLJ message were the likely sites through which Hfq exerted its
      posttranscriptional control. Consistent with the regulatory effects of Hfq,
      downstream genes controlled by FixLJ (such as nifK, noeB) were also subject to
      Hfq regulation in planta.

PMID- 27712148
TI  - Mental health and learning disabilities.
AB  - The Mental Health and Learning Disability Nurse Directors' and Leads' National
      Forum has launched a new website. The forum has a membership of 50 NHS
      organisations and its main aim is to provide a platform to support members to
      share ideas, policies and initiatives. Its website can be found at
      www.mentalhealthforum.org.uk.

PMID- 27712149
TI  - New chief nurse for Scotland appointed.
AB  - The Scottish Executive has appointed Paul Mar- tin to replace Anne Jarvie as
      Scotland's chief nursing officer (CNO) in September.

PMID- 27712150
TI  - Apathy over foundation status 'infects' staff.
AB  - The second group of NHS trusts was set to gain foundation status this month amid
      claims that the initiative is beleaguered by apathy.

PMID- 27712152
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27712151
TI  - HR with attitude.
AB  - Staff joining the NHS human resources (HR) team in England will benefit from a
      new web based induction course, writes Steven Black.

PMID- 27712153
TI  - England's chief nursing officer steps down this autumn. Nick Lipley reports.
AB  - Sarah Mullally (pictured left) has stressed that her decision to leave the
      Department of Health has been a 'personal career decision'. She said, however: 'I
      leave at a time when the nursing and allied health professions are well placed to
      provide continuing leadership in health care, and to continue to make a positive
      difference to the lives of many.' Ms Mullally added: 'I am proud to have played a
      part in introducing the changes that have put nurses and midwives at the
      forefront of better health care.

PMID- 27712154
TI  - Vantage point.
AB  - HERE'S A question for readers of Vantage Point: what is an 'arm's length body'?
      Sounds like something you might see after a nasty accident with a fishing rod,
      doesn't it?

PMID- 27712155
TI  - Sarah Mullally: from CNO to C of E.
AB  - Essence of care, modern matrons and nurse prescribing are among the areas of
      advance attributed England's chief nurse as she prepares to leave post this
      autumn.

PMID- 27712156
TI  - Preparing overseas nurses and midwives.
AB  - NHS Education for Scotland, in partnership with the Queen's Nursing Institute
      Scotland, has also been developing a Scotland wide programme to prepare overseas
      nurses and midwives.

PMID- 27712157
TI  - Getting it right in education.
AB  - More learning resources are being made available by organisations in Scotland.
      NHS Education for Scotland (NES) has launched Getting It Right Together, a
      learning resource produced with the Scottish Consortium for Learning Disability
      for pre-registration nursing students.

PMID- 27712158
TI  - School of leadership.
AB  - A new ebulletin has been launched by the NHSU. It features the latest
      developments and case studies from staff and learners who have used NHSU services
      and programmes.

PMID- 27712159
TI  - Travelling light.
AB  - WHEN BOSTON nurse Phil Jones graduated from nursing school four years ago, he
      took a job at a large city hospital. He quickly tired of the excessive workloads
      and felt he wasn't being paid enough. After only a year, he wanted out. He found
      a way to escape by becoming what is called a travel nurse.

PMID- 27712161
TI  - Conferences.

PMID- 27712160
TI  - Poll position.
AB  - SINCE THE establishment of foundation hospitals were announced, many nurses have
      talked about 'change fatigue', and have become suspicious about what they see as
      a move away from the principles of the national health service.

PMID- 27712162
TI  - Four per cent pay rise under agenda for change.
AB  - Senior nurses can expect pay rises of around 4 per cent when their trusts
      transfer over to the new Agenda for Change pay and grading system.

PMID- 27712163
TI  - Nurse nurse.

PMID- 27712164
TI  - New honours.
AB  - Jacqueline Docherty, director of nursing and operations at King's College
      Hospital, London, has been made a Dame of the British Empire in the Queen's
      Birthday honours list.

PMID- 27712165
TI  - Editorial.
AB  - SO WEare to have new chief nursing officers (CNOs) for England and Scotland.
      Sarah Mullally's surprise resignation last month paves the way for a new leader
      in England, while Paul Martin has been appointed Anne Jarvie's successor in
      Scotland. Maybe a new era for nurse leadership is in the offing?

PMID- 27712166
TI  - Danny Bungaroo.
AB  - What are your most important roles? I manage community nurses working across
      three multidisciplinary community learning dis- ability teams. I also provide
      direct clinical intervention to clients in one area and am involved in the
      learning disability service development strategies group.

PMID- 27712167
TI  - A vision for nursing research.
AB  - In previous editorials I have written about the need to ensure that a career in
      research is acknowledged as a real job trajectory option for nursing students and
      for nurses considering a career change. It is, therefore, with considerable
      satisfaction that I read the NHS Commissioning Board's Developing the Culture of
      Compassionate Care: Creating a New Vision for Nurses, Midwives and Care-givers
      (Department of Health 2012). Research and research careers are central to this
      draft vision.

PMID- 27712168
TI  - Designing Social Research - A Guide for the Bewildered Ian Greener Designing
      Social Research - A Guide for the Bewildered Sage Publications L22.99 224pp
      9781849201902 1849201900 [Formula: see text].
AB  - HOW TO design social research may be challenging for students but in this
      publication the author highlights the strengths and limitations of different
      approaches and advises on process and procedure.

PMID- 27712169
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27712170
TI  - The Patient Paradox: Why Sexed-up Medicine is Bad for Your Health Margaret
      McCartney The Patient Paradox: Why Sexed-up Medicine is Bad for Your Health
      Pinter & Martin L9.99 335pp 9781780660004 1780660006 [Formula: see text].
AB  - THIS BOOK offers a fascinating insight into the usefulness of modern medical
      screening. Practising GP Margaret McCartney bravely presents convincing and well
      constructed arguments against a number of screening programmes in the UK,
      including those for breast cancer, cardiovascular risk, prostate, and cervical
      cancer. She investigates the evidence behind the propaganda that often surrounds
      these services. The book is well written, easy to read and use of diagrams and
      examples is clear.

PMID- 27712171
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27712174
TI  - Barcode checks.
AB  - IN HEALTH CARE, we strive to achieve a seamless and safe system for our patients.
      We choose competent staff who, to our knowledge, will provide safe care, we have
      guidelines and policies and we accredit staff to ensure that they meet
      international standards.

PMID- 27712172
TI  - The future for research is bright.
AB  - CLAIRE HALE is the Dame Kathleen Raven professor of clinical nursing and co
      director of the academic and clinical unit for musculoskeletal nursing in the
      School of Healthcare at the University of Leeds. Having led the RCN's Research
      Society through a period of change in 2001, Claire was given an RCN Award of
      Merit.

PMID- 27712175
TI  - Exploring the evidence.
AB  - THE CLINICAL research facility (CRF) where I work opened in 2001 as one of five
      such 'millennial' organisations across the UK developed to translate scientific
      advances into better care.

PMID- 27712177
TI  - Treatment of aortic aneurysms.
AB  - Aortic aneurysms are common in older people but most are asymptomatic. Where
      symptoms do occur they include.

PMID- 27712176
TI  - Sexuality and Dementia: a guide for all staff working with people with dementia
      Carole Archibald Sexuality and Dementia: a guide for all staff working with
      people with dementia Second The Dementia Services Development Centre Stirling
      University 49 L12.00 1 85769 1865 1857691865 [Formula: see text].
AB  - This reasonably priced book is an essential resource for those working in the
      field of dementia care. It is written as a guide and presented in practical
      toolkit form, which includes case studies and reflective scenarios. It is also a
      useful resource for those working in gerontology.

PMID- 27712178
TI  - I'm still here John Zeisel I'm still here Piatkus L12.99 244pp 9780749952211
      0749952210 [Formula: see text].
AB  - THE AUTHOR of this book is better known in the united States for his work on arts
      and other cultural experiences with people with Alzheimer's disease. I'm Still
      here is a book that offers healthcare professionals, carers and the public an
      alternative perspective on dementia, especially Alzheimer's disease. underpinning
      the content are two values: the first about optimism in the skills and
      capabilities of people living with the disease; and the second about the need for
      vibrant relationships.

PMID- 27712179
TI  - Foot care for people with diabetes.
AB  - Foot complications are common in people with diabetes. Ulcers often become
      infected and, if not treated promptly, can result in sepsis and gangrene
      requiring amputation. The specialised nursing intervention in this study varied
      according to the assessed risk. Patients with diabetic neuropathy received
      treatment every six months. This comprised toenail cutting, trimming of
      trichophytic nail with a grinder, removal of keratinised layers of callus with a
      corn-cutter and grinding of the surface of the callus.

PMID- 27712180
TI  - Neuroscience nursing: evidence-based practice Sue Woodward Neuroscience nursing:
      evidence-based practice and Ann-Marie Mestecky (Eds) Wiley-Blackwell L39.99 680pp
      9781405163569 1405163569 [Formula: see text].
AB  - THIS BOOK provides a good overview for any nurse working with neurosurgical
      patients in acute settings, or those with chronic diseases such as epilepsy or
      myasthenia gravis. It introduces relevant anatomy and physiology and contains
      clear illustrations and tables. chapters on the assessment, interpretation and
      management of specific problems, such as raised intracranial pressure and altered
      consciousness, provide examples of common scenarios experienced in the specialty.

PMID- 27712182
TI  - When nurses hurt nurses When nurses hurt nurses Cheryl Dellasega Sigma Theta Tau
      International Honor Society of Nursing L18.70 225pp 1935476564 1935476564
      [Formula: see text].
AB  - THE CONCEPT of 'nurses hurting nurses' is interesting for a profession whose
      underlying values are that of compassion and care. Bullying stretches beyond one
      professional group, however. An organisational culture that promotes and allows
      such behaviour is toxic.

PMID- 27712183
TI  - Keeping Mum: Caring for Someone with Dementia Marianne Talbot Keeping Mum: Caring
      for Someone with Dementia Hay House L8.99 284pp 9781848502918 1848502915
      [Formula: see text].
AB  - AlTHOUGH THIS book focuses predominantly on a lay carer's experiences of caring
      for a relative with dementia in the UK it would be suitable for health and social
      care staff likely to encounter people with dementia and their carers. It
      highlights the need for staff to think outside their comfort zones and look at
      the lived experience of dementia.

PMID- 27712184
TI  - Talking about death.
AB  - A narrative approach was used to engage older adults in conversation about death
      in general and their own death in particular. Comments such as 'I am 89 now, how
      many more years do I have' and 'I don't want to go, I love this life. But it
      doesn't bother me,' suggest that people's anxiety about dying and fear decrease
      with age.

PMID- 27712185
TI  - Risks of taking antidepressants.
AB  - Older people with depression have higher rates of other diseases, particularly
      cerebrovascular disease. Therefore, they are at high risk of adverse events from
      antidepressants.

PMID- 27712186
TI  - Notice board.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27712187
TI  - Practice question.
AB  - Soline Jerram is nurse consultant older people and intermediate care, Berkshire
      Healthcare Foundation NHS Trust and chair of the nurses' and allied health
      professionals' special interest group, British Geriatrics Society.

PMID- 27712188
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27712189
TI  - A Computational Model of Osteochondral Defect Repair Following Implantation of
      Stem Cell-Laden Multiphase Scaffolds.
AB  - Developing successful tissue engineering strategies requires an understanding of
      how cells within an implanted scaffold interact with the host environment. The
      objective of this study was to use a computational mechanobiological model to
      explore how the design of a cell-laden scaffold influences the spatial formation
      of cartilage and bone within an osteochondral defect. Tissue differentiation was
      predicted using a previously developed model, in which cell fate depends on the
      local oxygen tension and the mechanical environment within a damaged joint. This
      model was first updated to include a rule through which mature cartilage was
      resistant to both terminal differentiation and vascularization, and then used to
      simulate osteochondral defect repair following the implantation of various cell
      free and cell-laden scaffolds. While delivery of a cell-free scaffold led to only
      marginal improvements in joint repair, implantation of a cell-laden bilayered
      scaffold was predicted to significantly increase cartilage formation in the
      chondral phase of the scaffold. Despite these improvements, bone still progressed
      into the chondral regions of these engineered implants by means of endochondral
      ossification during the later stages of repair. This led to thinning of the
      cartilage tissue, which in turn resulted in a prediction of increased tissue
      strain and, eventually, increases in fibrocartilage formation as a result of this
      altered mechanical stimulus. In contrast to this, the model predicted that
      implantation of a trilayered scaffold, which included a compact layer to confine
      angiogenesis to the osseous phase of the defect, further improves joint
      regeneration. This is achieved by allowing chondrogenically primed mesenchymal
      stem cells, which are seeded into the chondral phase of the implant, to form
      stable cartilage, which was ultimately resistant to both vascularization and
      endochondral ossification. These models provide a framework for exploring how
      environmental factors impact bone, cartilage, and joint regeneration and can be
      used to inform the design of new tissue engineering strategies for use in
      orthopedic medicine.

PMID- 27712194
TI  - Exercise-induced hypoalgesia: Pain tolerance, preference and tolerance for
      exercise intensity, and physiological correlates following dynamic circuit
      resistance exercise.
AB  - Previous research has demonstrated significant decreases in pain perception in
      healthy individuals following both aerobic and upper body resistance exercise,
      but research on circuit training has been limited. The purpose of the study was
      to determine the effects of a strenuous bout of dynamic circuit resistance
      exercise on pain threshold and pain tolerance in conjunction with changes in
      blood lactate levels, heart rate (HR), and perceived exertion. A sample of 24
      college-age students participated in 2 sessions: (1) a maximal strength testing
      session and (2) a circuit training bout of exercise that consisted of 3 sets of
      12 repetitions with a 1:1 work to rest ratio at 60% one-repetition maximum (1-RM)
      predicted from a three-repetition maximum (3-RM) for 9 exercises. Participants
      exhibited increases in pain tolerance, blood lactate levels, HR and perceived
      exertion following resistance exercise. Preference for exercise intensity was
      positively correlated with lactate post exercise and tolerance for exercise
      intensity was positively correlated with pain tolerance and lactate post
      exercise. In conclusion, this is the first study to demonstrate increases in pain
      tolerance following a dynamic circuit resistance exercise protocol and
      disposition for exercise intensity may influence lactate and pain responses to
      circuit resistance exercise.

PMID- 27712195
TI  - Information theoretic sub-network mining characterizes breast cancer subtypes in
      terms of cancer core mechanisms.
AB  - A breast cancer subtype classification scheme, PAM50, based on genetic
      information is widely accepted for clinical applications. On the other hands,
      experimental cancer biology studies have been successful in revealing the
      mechanisms of breast cancer and now the hallmarks of cancer have been determined
      to explain the core mechanisms of tumorigenesis. Thus, it is important to
      understand how the breast cancer subtypes are related to the cancer core
      mechanisms, but multiple studies are yet to address the hallmarks of breast
      cancer subtypes. Therefore, a new approach that can explain the differences among
      breast cancer subtypes in terms of cancer hallmarks is needed. We developed an
      information theoretic sub-network mining algorithm, differentially expressed sub
      network and pathway analysis (DeSPA), that retrieves tumor-related genes by
      mining a gene regulatory network (GRN) of transcription factors and miRNAs. With
      extensive experiments of the cancer genome atlas (TCGA) breast cancer sequencing
      data, we showed that our approach was able to select genes that belong to cancer
      core pathways such as DNA replication, cell cycle, p53 pathways while keeping the
      accuracy of breast cancer subtype classification comparable to that of PAM50. In
      addition, our method produces a regulatory network of TF, miRNA, and their target
      genes that distinguish breast cancer subtypes, which is confirmed by experimental
      studies in the literature.

PMID- 27712196
TI  - Identifying cancer type specific oncogenes and tumor suppressors using limited
      size data.
AB  - Cancer is a complex and heterogeneous genetic disease. Different mutations and
      dysregulated molecular mechanisms alter the pathways that lead to cell
      proliferation. In this paper, we explore a method which classifies genes into
      oncogenes (ONGs) and tumor suppressors. We optimize this method to identify
      specific (ONGs) and tumor suppressors for breast cancer, lung adenocarcinoma
      (LUAD), lung squamous cell carcinoma (LUSC) and colon adenocarcinoma (COAD),
      using data from the cancer genome atlas (TCGA). A set of genes were previously
      classified as ONGs and tumor suppressors across multiple cancer types (Science
      2013). Each gene was assigned an ONG score and a tumor suppressor score based on
      the frequency of its driver mutations across all variants from the catalogue of
      somatic mutations in cancer (COSMIC). We evaluate and optimize this approach
      within different cancer types from TCGA. We are able to determine known driver
      genes for each of the four cancer types. After establishing the baseline
      parameters for each cancer type, we identify new driver genes for each cancer
      type, and the molecular pathways that are highly affected by them. Our
      methodology is general and can be applied to different cancer subtypes to
      identify specific driver genes and improve personalized therapy.

PMID- 27712197
TI  - Realizing the potential of near-peer teaching programmes.

PMID- 27712198
TI  - Performance and physiological effects of different descending strategies for
      cross-country mountain biking.
AB  - This study investigated the performance-related feasibility and physiological
      benefits of purposefully eliminating propulsive work while descending in mountain
      biking and compared values to those measured during road descending. Participants
      cycled uphill on a road at race pace before descending over three conditions (off
      road pedalling; off-road coasting; road coasting). Relatively low power output
      during off-road pedalling was associated with a greater oxygen uptake (p < .01)
      when compared with off-road coasting despite no difference in vibration exposure
      (p > .05). Importantly, pedalling did not invoke a performance benefit (p > .05)
      on the descent used in this study. Significantly greater heart rate and oxygen
      uptake (both p < .01) were observed between road and off-road descending, likely
      caused by the increase in terrain-induced vibrations (p < .01) experienced
      between the bicycle and rider. Results indicate that reducing propulsive work
      during descending can improve recovery without being disadvantageous to
      performance. Similarly, the vibrations experienced during road descending are
      relatively low, and further reduce oxygen cost. In an effort to increase
      efficiency, it is recommended that mountain bike athletes focus on skills to
      increase descending speed without the addition of pedalling, and that equipment
      be used to decrease vibrations nearer to those seen on the road.

PMID- 27712199
TI  - Vital Notes for Nurses: Accountability Helen Caulfield Vital Notes for Nurses:
      Accountability Blackwell 192 L16.99 140512279X 140512279X [Formula: see text].
AB  - My knowledge and understanding of accountability is limited to the everyday, and
      could best be described as a 'working knowledge'. Thus, I came to this book with
      an open mind to see if it could fill knowledge gaps. It does what it says on the
      cover in that it presents, in notation form, an overview of accountability.

PMID- 27712200
TI  - Participatory Action Research in Health Care Tina Koch Participatory Action
      Research in Health Care Debbie Kralik Blackwell 186 L24.99 1405124164 1405124164
      [Formula: see text].
AB  - On first perusal, this book seemed ideal for healthcare professionals interested
      in developing public involvement or community development strategies. On closer
      inspection, however, the book is.

PMID- 27712201
TI  - The Research Process in Nursing Kate Gerrish The Research Process in Nursing Anne
      Lacey Blackwell 576 L19.99 140513013X 140513013X [Formula: see text].
AB  - Although there are an increasing number of texts available to nurses in respect
      of research, The Research Process in Nursing makes a unique contribution. It has
      stood the test of time having been in print since 1984, and has been a key text
      for many nurses wishing to learn about or undertake research. This complete
      revision brings a welcome updating of a comprehensive text which is grounded
      within UK nursing and nursing research.

PMID- 27712202
TI  - The right ingredients.
AB  - JAMIE OLIVER'Ssuccess in making school meals a hot political issue has led to
      calls for him to work his magic on hospital food.

PMID- 27712203
TI  - Community care overhaul causes 'dismay'.
AB  - Senior nurses are facing job losses and a major shake-up in career plans
      following the announcement of yet another radical overhaul of NHS organisations
      in England.

PMID- 27712204
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27712206
TI  - Future of senior staff in primary care high on NDA agenda.
AB  - The future of senior staff in primary care is set to be high on the agenda this
      month at the annual conference of the Nurse Directors Association (NDA).

PMID- 27712205
TI  - Serving up success.
AB  - THE FOCUS on NHS food this summer of England's chief medical officer Sir Liam
      Donaldson will be welcomed by many concerned with patient nutrition.

PMID- 27712207
TI  - Vantage point.
AB  - FOR MOST of us, partaking of nutrition is a normal and pleasurable experience
      that involves little risk. Moreover it is a basic need that we can fulfil for
      ourselves.

PMID- 27712209
TI  - Nurse leaders urged to encourage IT training.
AB  - Nurse managers have been urged to encourage staff to make the most of information
      technology (IT) training opportunities.

PMID- 27712208
TI  - Online training.
AB  - For online training programmes relating to other aspects of patient safety, visit
      The Health Professional Zone on the National Patient Safety Agency (NPSA) website
      www.npsa.nhs.uk/health/resources.

PMID- 27712210
TI  - ?
AB  - Screen break: nursing students Jackie Walsh, Laura Robinson and Liz Midgley join
      'matron' Sandra McQuat, a ward manager at Beatson Oncology Centre, the Western
      Infirmary, Glasgow, as they try out nurse training 1950s style for a new BBC
      series to be televised this autumn. The series, Thoroughly Modern Matron, was
      filmed at Belvoir Park Hospital, Belfast.

PMID- 27712211
TI  - ?
AB  - PROVIDING PATIENTS in hospital with the right food can be as important as
      providing them with the right medicine: it can literally save their lives.

PMID- 27712212
TI  - CMO report focuses on food.
AB  - Patient nutrition and NHS food provision have a central focus in the latest
      annual report by English chief medical officer Sir Liam Donaldson.

PMID- 27712213
TI  - Leadership awards.
AB  - Leaders in health care who would like to apply for two years of one-to-one
      coaching and personalised leadership development training can visit The Health
      Foundation website to find out about its Leadership Fellows award scheme.

PMID- 27712214
TI  - End of life care.
AB  - Those with a role in end of life care management might find the resources part of
      the NHS End of Life Care Programme website useful.

PMID- 27712215
TI  - Nurse migration.
AB  - The International Council of Nurses (ICN) and the Commission on Graduates of
      Foreign Nursing Schools (CGFNS) have launched a new website to develop, promote
      and disseminate research, policy and information on nurse migration, writes Ruth
      Williams.

PMID- 27712216
TI  - Nursing's losses and gains.
AB  - ONE OF the first papers I published in a nursing journal, back in 1979, was a
      personal account of caring for my father.

PMID- 27712217
TI  - Infection control.
AB  - With infection control in healthcare settings in the media spotlight, the
      Department of Health's (DH) toolkit for tackling the problem is particularly
      timely.

PMID- 27712219
TI  - Under cover.
AB  - HAVE YOU ever returned from a conference thinking that the best bits involved
      talking to colleagues at the coffee breaks?

PMID- 27712218
TI  - Dealing with disaster.
AB  - FOR MANY PEOPLE in London, July 7 2005 will always be recalled as the day that
      terrorist bombs were detonated on the capital's transport system. This will be
      especially true of the staff of the NHS acute trusts and emergency services who
      implemented major incident plans in response to the bombings.

PMID- 27712220
TI  - Karen Norman.
AB  - What gets you out of bed in the morning? Usually the noise from the bars across
      the road from where we live! Gibraltarians know how to party loud - and late!

PMID- 27712222
TI  - Have your say.

PMID- 27712221
TI  - Conferences.

PMID- 27712224
TI  - PCTs 'fail to appoint' directors.
AB  - Primary care trusts (PCTs) are coming under scrutiny amid claims that some are
      failing to appoint directors of nursing.

PMID- 27712225
TI  - Vantage point.
AB  - AS THE NEWLY configured primary care trust (PCT) boards in England slowly take
      shape, a fresh generation of PCT directors of nursing are taking stock of the
      work ahead.

PMID- 27712226
TI  - 5.4 per cent rise for top nurses PCTs 'fail to appoint' directors.
AB  - Nurse directors' average basic salaries increased 5.4 per cent to L80,530 last
      year, latest pay figures reveal.

PMID- 27712227
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27712228
TI  - Something fishy.
AB  - NEWLY ADMITTED patients on the medical wards at King's College Hospital, London,
      may notice some- thing a bit out of the ordinary about the uniforms of the staff
      taking care of them: many of them have brightly coloured fish brooches.

PMID- 27712229
TI  - Have your say.
AB  - Changes to how health care is delivered, particularly the provision of local,
      community based care for patients, has prompted the Department of Health to
      review the hospital travel costs scheme.

PMID- 27712230
TI  - Conferences.
AB  - RCN congress April 15-19 Harrogate Further details: RCN Events. Tel: 0207 647
      3577 Email: rcn.events@rcn.org.uk Website: www.rcn.org.uk.

PMID- 27712231
TI  - Ten steps to managing change.
AB  - CHANGE MANAGEMENT is a prime requirement of management. Change is all around us,
      and is happening every day. To some, this is exciting; they find it thrilling to
      be part of the action and to keep up with trends. But, to others, it can be
      threatening or even frightening.

PMID- 27712232
TI  - Joining forces: part 2.
AB  - THIS SECOND ARTICLE in Nursing Management's series on partnership considers how
      leaders can work with learning representatives on the clinical governance agenda.

PMID- 27712233
TI  - Odds-on favourite.
AB  - The recent announcement that the UK's first 'super-casino' will be built in
      Manchester has caused dismay in Blackpool, which had been tipped as favourite to
      win the licence.

PMID- 27712234
TI  - PbR 'should better reflect' nurse contribution.
AB  - The RCN is calling on ministers to ensure that the Payment by Results (PbR)
      tariff better reflects the contribution of nursing to the provision of NHS
      services.

PMID- 27712235
TI  - Guest editorial.
AB  - REFORMS, RECONFIGURATIONS and redesigns: these are the 'three Rs' that
      characterise the daily experience of staff in the NHS team, as much as the
      delivery of good patient care.

PMID- 27712236
TI  - Social enterprise.
AB  - The recent raft of government policies encouraging social enterprise in the
      healthcare services has prompted NHS Networks to add a section to its website
      that covers the concept.

PMID- 27712237
TI  - Implementing guidance.
AB  - If you have you been involved in implementing National Institute for Health and
      Clinical Excellence (NICE) guidance in your workplace, you can share your
      experiences on a new online database.

PMID- 27712238
TI  - Under cover Influencing people: The essential guide to thinking and working
      smarter Rogers Jenny [Formula: see text].
AB  - Effective leadership and an ability to influence others go hand in hand,
      particularly as competition over resources for healthcare services intensifies.

PMID- 27712239
TI  - At the centre of practice.
AB  - IN THE CURRENT climate of change, nurses need to respond quickly and
      appropriately to emerging challenges and to acquire rapid information about
      issues that affect quality of care.

PMID- 27712240
TI  - Mental health.
AB  - The Mental Health Foundation has revamped its website. Features include a weekly
      e-bulletin that delivers the latest news of developments in mental health, an
      online message posting service and discussion forums.

PMID- 27712241
TI  - Think lean.
AB  - 'Lean thinking' is a philosophy that requires the continuous elimination of waste
      or non-value-added elements from processes so that customers or patients are
      given ever greater value.

PMID- 27712243
TI  - Human Vaccines & Immunotherapeutics: News.

PMID- 27712242
TI  - Knowledge attitude and practice toward pertussis vaccination during pregnancy
      among pregnant and postpartum Italian women.
AB  - In Italy, no specific recommendation toward maternal pertussis immunization
      during pregnancy has been issued. However, vaccination during pregnancy will be
      likely integrated in the Italian immunization program in the future. In order to
      identify barriers to achieving a sufficient vaccination coverage during
      pregnancy, we investigated knowledge, attitude and practice toward pertussis
      vaccination during pregnancy through a web-based survey. A total of 343 Italian
      pregnant women (N = 164) and women in the postpartum period (N = 183) completed
      the online questionnaire. More than a half of the study population was uncertain
      regarding the benefits of the vaccination during pregnancy. Only 1.7% of women in
      the postpartum had received the vaccination during pregnancy, and 21% of pregnant
      women declared the intention to be vaccinated in pregnancy. Only 34% would accept
      the vaccination in the current or in a future pregnancy, if recommended by a
      physician, and a half would remain uncertain. Perceiving the vaccine as harmful
      for the fetus' development is associated to a decreased willingness to be
      vaccinated if recommended by a HCP, both in pregnant women (OR 0.25 p = 0.010 95%
      CI 0.09-0.72) and in women in the postpartum period (OR 0.32 p =  0.006 95% CI
      0.15-0.72). Our study suggests that the vaccination recommendation by physicians
      might not be sufficient to adequately raise vaccination coverage against
      pertussis among Italian pregnant women. A combination of educational
      interventions and tailored communi-cation campaigns could be implemented to
      promote maternal immunization.

PMID- 27712244
TI  - Letter from the editor.

PMID- 27712245
TI  - Universality and Diversity of Mental Health Concerns Across the Globe.

PMID- 27712246
TI  - What is the Evidence for Treating Delusional Disorder?

PMID- 27712247
TI  - Conferences.

PMID- 27712248
TI  - Resources.

PMID- 27712249
TI  - Nurse nurse.

PMID- 27712252
TI  - Overseas nurse numbers soar.
AB  - International nurses have once again hit the headlines, as health secretary Alan
      Milburn has been asked by the Royal College of Nursing to clarify which
      developing countries should not be targeted by trusts looking to recruit staff.

PMID- 27712251
TI  - Editorial.
AB  - The issue of nurse specialism is back on the agenda, although to be polite about
      it, the old chestnut can be traced back to Miss Nightingale's correspondence.
      Current concern arises from the different experiences that organisations have had
      with the creation of nurse consultant posts. Some have reported them to be
      roaring successes, though often without offering any specific outcomes that can
      be assessed or replicated. Some are more reserved but see them as a way of
      keeping able practitioners in their organisation. And some are asking, are they
      really worth it?

PMID- 27712253
TI  - Thousands of nursing recruits lost every year.
AB  - Thousands of new nursing recruits are lost every year, according to researchers
      at The King's Fund, and they are leaving the porofession as soon as they finish
      their training.

PMID- 27712254
TI  - Standards for care homes scrapped.
AB  - Standards setting minimum room sizes in care homes, among other things, have been
      scrapped.

PMID- 27712256
TI  - Websites.
AB  - RCN members now have even greater access to journals online. Following the
      setting up of a partnership deal with OVID, four more journals will be available
      in full-text versions on the internet.

PMID- 27712258
TI  - ?

PMID- 27712257
TI  - 'Negative experiences' force staff to quit public sector.
AB  - The United Kingdom's public sector is fighting a losing battle as it tries to
      hold on to staff, according to a survey by the Audit Commission. Respondents told
      the Commission that 'negative experiences' were forcing them to leave, and not
      the prospect of more attractive options elsewhere.

PMID- 27712259
TI  - Spirituality in health care contexts Helen Orchard Spirituality in health care
      contexts Jessica Kingsley 196 pages L15.95 1 85302 969 6 1853029696 [Formula: see
      text].
AB  - Spirituality in Health Care Contexts, edited by Helen Orchard is a much easier
      read. I found Mark Cobb's chapter on 'The moral foundations of chaplaincy'
      interesting and thought provoking, particularly his focus on the need for an
      educational and professional infrastructure to support competency amongst
      chaplains.

PMID- 27712260
TI  - The spiritual dimension of ageing Elizabeth MacKinlay The spiritual dimension of
      ageing Jessica Kingsl ey 304 pages L15.95 1 84310 008 184310008 [Formula: see
      text].
AB  - In terms of meeting the spiritual needs of patients, Elizabeth MacKinlay, in The
      Spiritual Dimension of Ageing, identifies that nurses must first understand their
      own spirituality if they are to understand the spirituality of others.

PMID- 27712261
TI  - Holistic care.
AB  - PROVIDING HOLISTIC HEALTHCARE that is seamless or 'joined up' and of the right
      quality is something that all healthcare clinicians should now be trying to
      achieve. I believe that, to date, nursing has been the champion of holistic care.
      However, recent exposure to the NHS, as a patient and as a worried daughter, have
      left me wondering whether this is still the case.

PMID- 27712262
TI  - Volunteers rewarded for dogged dedication.
AB  - Sunny the spaniel and owner Patrick Parry-Okeden (pictured) have been recognised
      for their volunteer work with older people at an Oxfordshire care home.

PMID- 27712264
TI  - NICE changes stance on treatment of Alzheimer's disease.
AB  - DRUGS WILL be available on the NHS for all people with Alzheimer's disease from
      this month after new guidance was published by the National Institute for Health
      and Clinical Excellence (NICE).

PMID- 27712263
TI  - Guide issued to help staff act on signs of malnutrition.
AB  - An information sheet to help health professionals and care home workers spot the
      signs of malnutrition and dehydration has been developed.

PMID- 27712265
TI  - Spiritual assessment in healthcare practice Wilfred McSherry Spiritual assessment
      in healthcare practice and Linda Ross M&K Publishing L27 190pp 9781905539277
      1905539274 [Formula: see text].
AB  - OLD AGE, sickness and death were defining moments in Buddha's search for
      spiritual enlightenment, and so it is for many of us faced with suffering as we
      start to question life and our place in it. Healthcare workers are frequently the
      ones who find themselves supporting the troubled person and their family. This
      book explores the nature of spirituality, in particular spiritual assessment.

PMID- 27712266
TI  - NHS lacks care, compassion and dignity.
AB  - THE NHS is failing to treat older people with care, compassion, dignity and
      respect, a report from the health service ombudsman concludes.

PMID- 27712267
TI  - Report criticises poorly maintained and inaccurate websites.
AB  - COUNCILS ARE letting older people and their families down by providing confusing
      and incorrect information about residential care on their websites, a report has
      found.

PMID- 27712268
TI  - Ensuring access to specialist care is fair.
AB  - Nurses working in care homes have a considerable impact on the health, wellbeing,
      social contact and overall quality of life of older people. Input from expert and
      specialist services can help us do this more effectively.

PMID- 27712271
TI  - Pupils drum up support for new therapy.
AB  - THE POWER of music and rhythm is being used to unite different generations and
      cultures at one care home.

PMID- 27712272
TI  - Diary.

PMID- 27712273
TI  - Practice question.
AB  - Dawne Garrett is consultant nurse intermediate care at Bournemouth and Poole
      Community Health Services In 2008 a letter was sent to 826 residential homes in
      one state in Australia asking them what information was available that addressed
      issues of intimacy and sexuality. Less that 20 per cent responded and of those 64
      per cent said they had no information available on the topic ( Bauer et al 2008
      ).

PMID- 27712274
TI  - Notice board.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27712275
TI  - Medication that triggers delirium.
AB  - The pathophysiology of delirium is complex and not completely understood.
      Medications are an important risk factor and may be the sole cause in 12-39 per
      cent of cases.

PMID- 27712276
TI  - Toolkit to enhance quality of life for people with dementia.
AB  - This study aimed to develop a practical tool to support quality of life in
      dementia. Group discussions including professionals, people living with dementia
      and other intereste lay people developed a dementia toolkit for effective
      communication (DEMTEC) which, once completed, will be available free, via the
      internet.

PMID- 27712279
TI  - Feedback on being in hospital.
AB  - Four clinicians and four consumers over 70 years of age took part in workshops to
      reflect on aspects of care for older people in acute hospitals. One of the themes
      their discussion generated was problems with food. Packaging was hard to open and
      ensuring that patients had eaten was not considered as important as giving
      medication. A further example of the lack of importance given to nutrition was
      the loss of technical aids for eating supplied by occupational therapists.

PMID- 27712280
TI  - Step up to the mark, leaders.
AB  - These are challenging times for all of us. Reconfiguration, redundancy and
      redeployment abound and uncertainty is often the only certainty. The pressure on
      individuals can feel immense but this is not the era for the faint hearted. This
      is the time for real leaders to come to the fore, focus on the horizon and create
      the future.

PMID- 27712282
TI  - Older people.
AB  - A new website has been launched by the British Geriatrics Society (BGS) to
      provide access to information on the specialist care of older people. The site
      has a resources section that includes best-practice guides, clinical guidelines,
      consultation responses and the BGS bi-monthly newsletter. It also includes
      information on disease-specific conditions, general clinical management of frail
      older people and developments in the provision of health care such as
      commissioning, health economics and end of life care.

PMID- 27712281
TI  - More holes than cheese. What prevents the delivery of effective, high quality and
      safe health care in England?
AB  - What prevents the delivery of effective, high quality and safe health care in the
      National Health Service (NHS) in England? This paper presents 760 challenges
      which 330 NHS staff reported as preventing the delivery of effective, high
      quality and safe care. Some problems have been known for over 25 years (staff
      shortages, finance and patient complexity) but other challenges raise questions
      about the commitment of the NHS to patient and staff safety. For example,
      Organisational Culture leading to 'stifling bureaucracy', 'odds stacked against
      smooth [...] working' and Workload resulting in 'firefighting daily' and
      'perpetual crisis mode'. The role of Human Factors/Ergonomics professional input
      (engagement with safety scientists) is discussed in the context of success
      stories and examples of Human Factors Integration from other safety critical
      industries (Defence, Nuclear and Rail). Practitioner Summary: 760 challenges to
      the quality, effectiveness and safety of health care were identified at Human
      Factors/Ergonomics taster workshops in England. These are used to challenge
      health care providers to think about a Human Factors Integration (HFI systems)
      approach for safety, well-being and performance for all people involved in
      providing and receiving health care.

PMID- 27712285
TI  - Safeguarding children in primary health care Julie Taylor Safeguarding children
      in primary health care and Markus Themessl-Huber (Eds) Jessica Kingsley L19.99
      272pp 19781843106524 1843106523 [Formula: see text].
AB  - THIS BOOK is an in-depth exploration from a multidisciplinary perspective of the
      management of neglect and the physical, sexual and emotional abuse of children.

PMID- 27712284
TI  - Tailored leadership.
AB  - I HAVE worked in community services for the past 21 years, and in clinical and
      operational roles supporting the head of nursing for the past five. I have
      responsibility for a round-the-clock district nursing service, district nurse
      liaison and a community phlebotomy service.

PMID- 27712286
TI  - Non-executive directors.
AB  - A new professional networking site has been created for the NHS Alliance's non
      executive director network (NEDNET). The website uses OnMedica's professional
      networking platform to provide a secure online environment in which NEDNET
      members can share information and best practice. The network aims to help non
      executive directors find theirpeers, learn from each other and learn about the
      latest developments. The website can be found at www.medefero.com/nednet.

PMID- 27712287
TI  - Global nursing.
AB  - WHEN NURSES come together for international events, discussion at some point
      turns to nurse leadership, a common concern across the globe.

PMID- 27712289
TI  - Cancer care.
AB  - The Northern Ireland Cancer Network (NICaN) has developed a new e-learning
      programme on the care of people who have undergone laryngectomy. The programme is
      divided into modules, which cover a range of topics from emergency to community
      care, and each module uses quizzes to assess learning. Participants can do all
      the modules or choose the ones most relevant to their area of practice. For more
      information, go to www.cancerni.net/education/elearningcareofthelaryngectomee .

PMID- 27712288
TI  - Service commissioning.
AB  - The Royal Society for Public Health (RSPH) has published a Guide for World Class
      Commissioners: Promoting Health and Well-Being. Reducing Inequalities. Funded by
      the Department of Health, the guide explains how to enhance the commissioning of
      local services. Senior nurses involved in preventative, community and chronic
      care services can use the guide, which is available to download free at
      www.rsph.org.uk/en/policy-and-projects/projects/commissioning-tool-for-health
      promotion.cfm , to help ensure they are engaged with the commissioning process.

PMID- 27712290
TI  - Independent sector.
AB  - A guide to dispel some of the myths of working in the independent healthcare
      sector has been launched by Skills for Health.

PMID- 27712291
TI  - Out for consultation.
AB  - Nursing strategy The Department of Health, Social Services and Public Safety
      (DHSSPS) has launched a strategy for nursing and midwifery in Northern Ireland
      and is seeking views on the proposals. The strategy was developed in response to
      the Modernising Nursing Careers agenda and is similar to that which concerns the
      Midwifery 2020 initiative. The document can be read, and responses to it made, at
      www.dhsspsni.gov.uk/showconsultations?txtid=40605 . The closing date is April 19.

PMID- 27712293
TI  - Get connected.
AB  - As MANAGERS, we tend to look forward, to plan and to anticipate where the next
      challenges are likely to come from. finding time to reflect on events is
      therefore difficult.

PMID- 27712292
TI  - PM's commission calls for 'champions of change'.
AB  - THE REPORT by the Prime Minister's Commission on the Future of Nursing and
      Midwifery in England has been welcomed by health organisations and is expected to
      raise the status of the professions as leaders in care.

PMID- 27712294
TI  - Improving nursing by degrees.
AB  - It has been my privilege to be part of the prime minister's commission on the
      future of nursing and midwifery in England.

PMID- 27712298
TI  - Nurse executives urged to think of different ways to improve patient care.
AB  - PATIENT SAFETY and the quality of clinical care have soared up the NHS agenda in
      the past 12 months.

PMID- 27712297
TI  - Prime minister's commission findings get mixed response.
AB  - WHEN PRIME minister Gordon Brown launched a commission to examine the future of
      nursing and midwifery last year, there was an expectation that it would
      rejuvenate the profession in England.

PMID- 27712300
TI  - Mid Staffs inquiry finds that 'lack of leadership' contributed to deaths.
AB  - A LACK of leadership at ward and board level contributed to the unnecessary
      deaths of at least 400 patients at Mid Staffordshire NHS Foundation Trust, a
      report has found.

PMID- 27712299
TI  - In a flash.
AB  - Pocket-sized flash cards are helping nurses at one hospital to identify if
      patients admitted with physical illnesses or injuries also have mental health
      conditions.

PMID- 27712301
TI  - Senior nurses judged crucial to success of productive ward.
AB  - THE EFFECTIVENESS of the productive ward programme depends on the support and
      guidance nurses receive from senior nursing leaders in their organisations,
      research has revealed.

PMID- 27712302
TI  - Saving lives, saving money.
AB  - AS THE NHS moves into a period of financial restraint, the temptation to cut
      corners, eliminate non-core activities and bleed cash from services is likely to
      become increasingly strong.

PMID- 27712303
TI  - Making collaboration work.
AB  - The Children's Hospitals Network (CHN) was formed in 2012 following a review of
      national specialist services. Oxford University Hospitals NHS Foundation Trust
      (OUH) and the University Hospital Southampton NHS Foundation Trust (UHS)
      collaborated in its formation, with the CHN hosting clinical and operational
      networks across more than 20 district general hospitals in the Thames Valley and
      Wessex regions.

PMID- 27712304
TI  - In other RCNi journals.
AB  - 'Healthcare professionals need greater awareness of the features of benign
      neonatal sleep myoclonus to reduce the number of neonates undergoing unnecessary
      investigations and avoid misdiagnosis of the condition as epilepsy.'

PMID- 27712305
TI  - A three-stage process for change management.
AB  - Healthcare organisations are continually undergoing change. If such change is not
      managed well, it can affect a number of areas, including staff turnover, patient
      care and on budgetary targets.

PMID- 27712306
TI  - Diagnosing and managing brain tumours in children.
AB  - Brain tumours account for more than one quarter of all cancers and are the most
      common cause of cancer-related death among children in the UK.

PMID- 27712307
TI  - Seizures in children.
AB  - Defined as a sudden surge of electrical activity in the brain, a seizure will
      usually affect how a person acts for a short time.

PMID- 27712308
TI  - Consistency in end of life care.
AB  - The death of a child is a comparatively rare event in the UK. Even so, more than
      3,000 infant and 2,000 children and young people age 1-19 years died in England
      and Wales in 2012.

PMID- 27712309
TI  - Charity launches video campaign.
AB  - The charity Together for Short Lives (TSL), which supports families of children
      with life-shortening conditions, has launched a campaign called You Can Be That
      Nurse to lure staff into the sector.

PMID- 27712310
TI  - We need school nurses now more than ever.
AB  - School nurses are in a unique position to spot the early signs of abuse in
      children, but evidence suggests that this aspect of their role is being
      compromised.

PMID- 27712314
TI  - Taking a new path.
AB  - We would not place a child on a bicycle designed for an adult and expect them to
      pedal or steer it. So why would we apply adult theories of nursing to children?

PMID- 27712311
TI  - Picture book support for preparing children ahead of and during day surgery.
AB  - Aim To develop and evaluate the use of a specific picture book aiming to prepare
      children for anaesthesia and surgery. Methods An intervention comparing two
      different information methods before ear, nose and throat day surgery was
      performed. The intervention involved using a specific information sheet and a
      specific picture book. Parents (n=104) of children aged 2-12 years completed open
      ended questions that were analysed with qualitative content analysis. They were
      divided into two groups: one group received routine information and one received
      routine information and the intervention. Findings The picture sheet and picture
      book were valuable aids to prepare small children for anaesthesia and surgery by
      explaining the procedures that would take place. The parents expressed that
      knowledge of the procedures made them and the child feel secure. Conclusion Peri
      operative information through pictures supports children and their parents during
      day surgery and may be helpful in future healthcare visits.

PMID- 27712315
TI  - Millions to be affected by expected rise in pollen count.
AB  - Back to school misery could be compounded for schoolchildren in future as numbers
      suffering from hay fever caused by ragweed pollen is expected to double in Europe
      within 35 years.

PMID- 27712316
TI  - Helping people through their darkest hours.
AB  - On my last placement I met two wonderful people who were in the most frightening
      situation parents can find themselves in.

PMID- 27712317
TI  - Nurses struggle to help pupils with long-term conditions.
AB  - Most school nurses are not confident they can give essential support to pupils
      with long-term health conditions. Research by the National Children's Bureau
      found that, due to heavy workloads and the need to work across several schools,
      nine out of ten school nurses were less confident they can help children with
      conditions such as diabetes and asthma.

PMID- 27712318
TI  - Support for families.
AB  - Families need support to understand the implications of screening results.

PMID- 27712319
TI  - Sickle cell and cystic fibrosis carrier results.
AB  - Background Newborn screening (NBS) is used to identify pre-symptomatic babies who
      carry, or are affected by, genetic or congenital conditions ( UK Newborn
      Screening Programme Centre 2012 ). In England, parents are required to provide
      informed consent before their babies are screened.

PMID- 27712322
TI  - Bronchiolitis.
AB  - In England last year, nearly 40,000 babies and young children with bronchiolitis
      were admitted to hospital. This infection is usually caused by the respiratory
      syncytial virus, and in most cases symptoms are mild and last only a few days.
      However, a quality standard published in the summer by the National Institute for
      Health and Care Excellence (NICE) states that admissions for bronchiolitis are
      rising. NICE quality standards describe high-priority areas for improvement in a
      defined field of care.

PMID- 27712324
TI  - How holistic nursing can enhance the quality of life of children with cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is one of the most common life-limiting genetic conditions.
      This article presents a case study of a teenager with one of the rarer
      presentations of CF. This case study explores the experiences of her and her
      family. It also discusses the effects of CF on the patient and her family, and
      how it affects their quality of life and well-being.

PMID- 27712326
TI  - Nurse-initiated and criteria-led discharge from hospital for children and young
      people.
AB  - The readiness of a child or young person for discharge includes patient safety,
      the family's ability to care for the child at home and the ongoing treatment they
      will need, which has a direct influence on their health outcomes and future
      readmissions to hospital. There are no standard criteria for discharge practice
      and registered nurses have reported concerns about their ability to provide
      education and discharge planning to meet the needs of the patient and their
      family. A literature review was carried out to ascertain the current discharge
      principles adhered to in practice and the implemented tools used. The problems
      faced by registered nurses include ineffective communication, poorly defined role
      in discharge planning and lack of agreement with the multidisciplinary team. The
      standardisation of discharge procedures may reduce the risk of readmission and
      health deterioration of the patient and ensure positive health outcomes, improve
      family health literacy and continuity of care.

PMID- 27712330
TI  - College calls for protected funding for health visitors as number of posts falls.
AB  - The RCN has called for protected funding for health visitors as latest workforce
      figures showed hundreds fewer posts in recent months.

PMID- 27712327
TI  - Understanding the endocrinopathies associated with the treatment of childhood
      cancer: part 1.
AB  - This article explores endocrinopathies associated with late effects of treatments
      for childhood cancers. It is the first of two articles on the subject, the second
      to be published in November. This is a growing area of care, as more than 80% of
      all childhood cancer is treatable, resulting in an increase in survivors of
      childhood cancer. However, up to two thirds of these children are reported to
      present with significant health problems resulting from their treatments, and
      approximately 25% of survivors have endocrine problems. This article explains how
      an understanding of oncology and endocrinology enables nurse specialists to
      educate young people about their past treatment and its implications for their
      health. This knowledge is the foundation for individually-tailored care plans
      that enable young people to be confident to self-care and self-monitor their long
      term health.

PMID- 27712331
TI  - Guide for staff concerned about children sexting.
AB  - Nurses' concerns about children sexting and sharing sexual images should always
      be followed up, according to new guidance.

PMID- 27712332
TI  - Higher risk of developing diabetes from weight gain during puberty.
AB  - Teenagers' tendency to put on weight at puberty has been linked to a sudden drop
      in the calories burned while resting, in a new study. When girls and boys reach
      puberty there is a rapid drop in calories burned, which is counter-intuitive as
      calories burned could be expected to rise with the growth spurt.

PMID- 27712333
TI  - Lack of room keeps families apart.
AB  - Thousands of parents of sick or premature babies cannot be closely involved in
      their child's hospital care due to inadequate support services, a new report has
      found.

PMID- 27712334
TI  - Other scans.

PMID- 27712335
TI  - We need to attract more students to palliative care.
AB  - A good palliative care service is responsive, available to families where they
      want it, provided round the clock, and co-ordinated by a lead healthcare
      professional or team. This is the view of one hospice director of care in
      response to a draft good practice guideline on end of life care from the National
      Institute for Health and Care Excellence.

PMID- 27712336
TI  - Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome is a congenital condition that can affect many of a
      child's systems. It was named after the Dutch paediatrician who first identified
      it.

PMID- 27712337
TI  - How to use social media to disseminate research findings.
AB  - Traditionally, research and theoretical studies have been disseminated through
      articles published in journals, or via conferences as oral or poster
      presentations. However, the rise of the internet, particularly social media, has
      broadened opportunities.

PMID- 27712338
TI  - Overcoming the ignorance of basic sex education.
AB  - Another academic year is underway, and schools in England can again choose
      whether or not to teach sex and relationships education (SRE). The evidence in
      favour of making SRE a requirement in all schools is stacked higher than ever.
      One girl in four starts her period before she has learned about it, and 38% of
      boys do not learn anything about wet dreams before they experience them ( Sex
      Education Forum (SEF) 2016a ), which shows that even biological aspects of SRE
      are falling short.

PMID- 27712340
TI  - Cultural Awareness in Nursing and Health Care Second edition Karen Holland
      Cultural Awareness in Nursing and Health Care Second edition and Christine Hogg
      Hodder Arnold L21.99 208pp 9780340972908 0340972904 [Formula: see text].
AB  - THIS IS the second edition of a useful and practical text that examines issues of
      culture, race and ethnicity as they affect patient care. It is aimed at students
      but will appeal to qualified health and social care professionals.

PMID- 27712339
TI  - Doing a Literature Review in Health and Social Care A Practical Guide Second
      edition Helen Aveyard Doing a Literature Review in Health and Social Care A
      Practical Guide Second edition McGraw Hil / L17.99 170pp 9780335238859 0335238858
      [Formula: see text].
AB  - LITERATURE REVIEWS are an important preliminary step towards a research project
      or dissertation, as well as being an important source of information in their own
      right. But despite their value, literature reviews often present a major
      challenge to students at undergraduate and postgraduate level.

PMID- 27712342
TI  - The driving force in research.
AB  - At the Royal College of Nursing annual international nursing research Conference
      in Harrogate it was noticeable that clinical research nurses(CRNs) had real
      presence. They hosted a packed symposium and presented concurrent papers and
      posters.

PMID- 27712343
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27712344
TI  - Doing Quantitative Research in Education with SPSS Second edition Daniel Muijs
      Doing Quantitative Research in Education with SPSS Second edition L24.99 264pp
      9781849203241 1849203245 [Formula: see text].
AB  - THIS TEXT is a straightforward, no nonsense guide for novice researchers
      venturing into research involving quantitative methodologies. It is also an
      excellent resource to refresh more experienced researchers. It is well written in
      plain English and encourages researchers to carry out their own analyses.

PMID- 27712345
TI  - Doing Your Literature Review - Traditional and Systematic Techniques Jill K
      Jesson Doing Your Literature Review - Traditional and Systematic Techniques ,
      Lydia Matheson Fiona M Lacey L20.99 192pp 9781848601543 1848601549 [Formula: see
      text].
AB  - A PLETHORA of books has appeared over the past few years on writing literature
      reviews. However this one is definitely worth a second look. Written by a social
      scientist, a pharmaceutical scientist and a library scientist, the authors
      between them have a wealth of experience and authority on the subject.

PMID- 27712346
TI  - Using mixed methods David Plowright L24.99 224pp 9781848601086 1848601085
      [Formula: see text].
AB  - INITIAL PERUSAL of the content of this publication did not reveal anything new.
      However, this book is well presented and has plenty of tables which help simplify
      what is often a dense subject.

PMID- 27712347
TI  - About the journal.
AB  - Aims Nurse Researcher seeks to promote professional excellence and encourage
      creativity in nursing. Nurse Researcher is editorially independent and the
      opinions expressed in it are not those of the RCN, nor of any contributor's
      employing organisation, unless specifically stated. All profits generated by RCN
      Publishing will be used to benefit nurses and nursing.

PMID- 27712348
TI  - Insight into the challenges faced by students involved in real-world research.
AB  - A COLLECTION of papers focusing on 'challenges in real world research' could have
      provided multiple examples of the unusual and the bizarre. I could have submitted
      one myself on the array of extravagant and eccentric individuals and situations
      that have helped and hindered my research endeavours: the men who were women, the
      knives and the threats, the comedic and the tragic.

PMID- 27712349
TI  - Research is part of real life.
AB  - The transition from nursing student to registered nurse can be a challenging one
      as newly qualified nurses come face-to-face with the real world of practice. More
      than ever before, universities are aware of the need to help students make this
      transition by ensuring that classroom learning and assignments are as practically
      focused as possible.

PMID- 27712352
TI  - Designing and managing your research project David R Thomas and Ian D Hodges
      Designing and managing your research project Sage Publications L20.99 264pp
      9781848601932 184860193X [Formula: see text].
AB  - THIS TEXT book is aimed at providing new researchers in health and social care
      with a general introduction to the fundamental elements of managing a research
      project. It offers 14 detailed chapters that examine a range of issues that apply
      to conducting research, including software skills, developing research
      objectives, writing proposals, doing literature reviews, working with colleagues
      and supervisors. While appropriate theoretical insights are provided the emphasis
      is on practical application and the book is particularly useful in this regard.

PMID- 27712350
TI  - Meta-analyses of clinical neuropsychological tests of executive dysfunction and
      impulsivity in alcohol use disorder.
AB  - BACKGROUND: Promising models for cognitive rehabilitation in alcohol treatment
      rest on a more nuanced understanding of the associated impairments in the
      multifaceted domains of executive functioning (EF) and impulsivity. OBJECTIVES:
      This meta-analysis examined the effects of alcohol on the individual
      subcomponents of EF and impulsivity in recently detoxified participants,
      including 1) Inhibition & Self-Regulation, 2) Flexibility & Set Shifting, 3)
      Planning & Problem Solving, 4) Reasoning & Abstraction, and 5) Verbal Fluency.
      Impulsivity was further examined through an analysis of motor, cognitive, and
      decisional subcategories. METHOD: Investigators searched, coded, and calculated
      effect sizes of impairments demonstrated in a broad range of neuropsychological
      tests for EF. A total of 77 studies were selected covering 48 years of research
      with a sample size of 5140. RESULTS: Findings ranged from a Hedges' g effect size
      of 0.803 for Inhibition to a Hedges' g of 0.359 for Verbal Fluency. Results also
      varied for the individual subcategories of Inhibition, including a large effect
      size for decisional impulsivity (g = 0.817) and cognitive impulsivity (0.860),
      and a moderate effect size for motor impulsivity (g = 0.529). The Hayling Test,
      Wisconsin Card Sorting Test, and Iowa Gambling Task were the measures most
      sensitive for alcohol effects. CONCLUSION: Planning, problem solving, and
      inhibitory abilities are significantly affected by alcohol abuse, with decisional
      and cognitive forms of impulsivity most impacted. Cognitive remediation targeting
      these deficits might increase the related functions that mediate the ability to
      moderate or abstain from alcohol, and so lead to improved treatment results.

PMID- 27712354
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27712353
TI  - Guided Reflection: A Narrative Approach to Advancing Professional Practice Second
      edition Christopher Johns Guided Reflection: A Narrative Approach to Advancing
      Professional Practice Second edition (Ed) Wiley-Blackwell L32.99 320pp
      9781405185684 1405185686 [Formula: see text].
AB  - THIS SECOND edition builds on the first and gives a rich account of Johns's
      evolving views from the reflective turn in his first edition to the narrative
      turn proposed here. The subheadings within each chapter guide the reader but each
      chapter should be read in its entirety to appreciate fully the unfolding
      narratives. The book will appeal to practitioners and researchers involved in
      reflexive narrative research because the style adopted illustrates how
      theoretical perspectives can be woven in with the narratives.

PMID- 27712355
TI  - Supervisory support for students.
AB  - With the academic year under way, many students are beginning to think about
      research projects. They will identify or be allocated a supervisor whose job it
      is to guide them through what might feel like methodological soup with seemingly
      impossible deadlines.

PMID- 27712357
TI  - Research methodology: a step by step guide for beginners Ranjit Kumar Research
      methodology: a step by step guide for beginners Sage L26.99 440pp 9781849203012
      1849203016 [Formula: see text].
AB  - THIS IS a practical introductory text for healthcare students with minimal
      understanding of the research process. The focus of the text integrates
      quantitative and qualitative methodologies through the following operational
      steps.

PMID- 27712356
TI  - At the heart of nursing.
AB  - Evidence-based practice challenges nurses to base their decision making on the
      best available evidence. This is a requirement for all nurses so it is not
      surprising that the move to all-graduate nurse training in the UK has been
      accompanied by increased research content in curricula and a greater focus on the
      need to use evidence throughout programmes of study.

PMID- 27712358
TI  - Leading change in healthcare Anthony L Suchman , David J Sluyter and Penelope R
      Williamson Leading change in healthcare Radcliffe L35 362pp 9781846194481
      1846194482 [Formula: see text].
AB  - WHEN A book promises to offer an alternative to the 'antiquated and
      psychologically unsophisticated theories' that have underpinned the leadership of
      change programmes to date, you can expect the interest of any forward-thinking
      manager, clinician or academic in the field to be piqued.

PMID- 27712359
TI  - Theory and methods in social research Bridget Somekh Theory and methods in social
      research Cathy Lewin (Eds) Sage L24.99 368pp 9781849200158 1849200157 [Formula:
      see text].
AB  - Rather than your typical 'how to' approach, this book offers a cross-perspective
      that challenges the thinking on how to conduct research and how to draw on
      sources through strategies and experiences. The reader finishes with an
      understanding of conducting well-conceptualised research because the text is easy
      to understand and remember, and applies to other disciplines.

PMID- 27712360
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27712361
TI  - Group that celebrates silliness helps women cope with growing old.
AB  - How older women cope with challenges and losses in later life influences not only
      their physical health, but also their psychological wellbeing and quality of
      life. The Red Hat Society is an international social group for women over 50, and
      has a mission to 'celebrate the silliness of life'; the main feature of society's
      meetings is that members must dress up in gaudy red hats and garish purple
      outfits. The women interviewed said participation helped them to cope with
      emotional stressors of later life. Although growing old is not something that can
      be changed, participation in the society helps circumstances seem less
      distressing and more manageable.

PMID- 27712362
TI  - One chance to get it right.
AB  - Recently I chaired a conference hosted by the National Council for Palliative
      Care focusing on the issues of comorbidity and dying with dignity. Being a
      conference chair is one sure way of concentrating your mind and thoughts on
      speaker presentations because you have to pick up the threads, link speakers
      together and summarise the conference.

PMID- 27712363
TI  - Toolkit for falls service.
AB  - The government is set to launch a toolkit to help primary care trusts (PCTs)
      develop falls and fractures services for older people to boost access across the
      country.

PMID- 27712364
TI  - Welsh debate the future of social care.
AB  - On November 11, Wales began a national debate on how to pay for social care in
      the future. Amid warnings of a L360 million funding gap in social services in 20
      years' time, the Welsh public is being asked to consider how much they are
      willing to contribute from their personal finances to social care.

PMID- 27712365
TI  - ?
AB  - Former athletics star, Colin Jackson, presented an award to a team from Bristol
      based Brunelcare last month in recognition of the company's training in 'Person-
      Centred Care' that it offers its staff. The charity, which offers care services
      for older people in residential accommodation and their own homes across the
      South West, has developed a specialist dementia care programme. Maureen Howe, who
      spearheaded the training programme, said: 'Although the standard of care within
      our care homes was good, we wanted to be much better at meeting the needs of
      people living with a dementia. We wanted to change the culture of care from being
      task-based to person-centred, seeing each resident for the unique person they
      are. The training was for everyone, not just the care staff so it encompassed
      admin, laundry staff, catering staff, everyone.'

PMID- 27712366
TI  - Early discharge fuels A&E visits.
AB  - Millie was wearing her nightie and didn't have enough clothes when she was
      discharged from hospital. Staff decided to buy her a dress from the hospital
      charity shop. Despite being in her eighties and having a heart condition, she was
      dropped off on her doorstep in her bedroom slippers and no one made sure she got
      inside safely. She had no care plan or medication. This is the story Millie's
      daughter told Age Concern when she got in touch.

PMID- 27712367
TI  - Championing dignity.
AB  - Encouraging compassion Ruth Chauhan has been passionate about improving care for
      older people for the past 25 years, and she recently became a dignity champion.
      Like so many healthcare professionals, she believes everyone has the right to be
      treated with dignity and respect, and that empathy and compassion in care are
      just as important as having the knowledge and skills to carry out clinical tasks.

PMID- 27712368
TI  - Learn more about mental health care.
AB  - As I write this editorial, I am visiting Wollongong University, New South Wales,
      Australia, where, through a partnership initiative with United Care, I am
      learning more about the care of older people in Australia. I am struck by the
      fact that many of the concerns and issues regarding the care of older people are
      the same on both sides of the world.

PMID- 27712369
TI  - Thailand.
AB  - Growing complaints Speaking at a government policy forum on how to improve
      services for older people, a senior minister in Thailand's Social Development and
      Human Security Ministry told of a growing number of complaints about nursing
      care. Ubon Limsakul called for standards to be set. According to Dr Nonglak
      Pagaiya, an academic at the Human Resource for Health Research and Development
      Office, there are 97,972 registered nurses in the country, less than one quarter
      of whom are taking care of older people. Dr Siriphan Sasat of the Chulalongkorn
      University's Faculty of Nursing called for the establishment of a national level
      committee to tackle problems relating to the care given to the older people.

PMID- 27712370
TI  - Gill Duncan.
AB  - At school I wanted to follow in my mum's footsteps to be a nurse. I had my
      interview to train at the Oxford Radcliffe school of nursing when I was 16.

PMID- 27712371
TI  - Link nurse's role hampered by lack of management support.
AB  - Link nurses should have background knowledge of palliative care, be able to
      support and develop others and be in a position to implement change. This paper
      explored link nurses' views of supports and barriers to implementation of the
      role in the nursing home. The nurses found external support, monthly meetings and
      access to a resource file helpful but were hindered by lack of management
      support, a transient workforce and lack of preparation for the role.

PMID- 27712372
TI  - Israel.
AB  - Credit crunch hits pensioners The credit crunch is hitting older people in
      Jerusalem particularly hard, say several organisations who work with this age
      group. They are calling for the government to cancel plans to raise the income
      threshold for eligibility for nursing care assistance, as they say this could
      deprive 30,000 senior citizens of home help.

PMID- 27712373
TI  - The four-hour waiting target in A&E is not always helping older people.
AB  - The Department of Health document, The NHS Plan, stated that no patient should
      wait more than four hours in Accident and Emergency (A&E). Nurses argue that the
      pressures of meeting the four-hour target have led to hasty transfers to other
      departments, often with incomplete assessments and misdiagnosis. Transferring
      patients in this manner poses problems for the ward and for the older person,
      particularly those with dementia who are further disorientated by multiple moves.

PMID- 27712374
TI  - Scientific approach to nursing recommended.
AB  - Parameters that are particularly important to the nursing care of older people
      feature heavily in a new report by researchers at the National Nursing Research
      Unit at King's College, London, which is aimed at helping nurses see the impact
      of the care they deliver.

PMID- 27712375
TI  - United states.
AB  - Oral hygiene care reduces risk of pneumonia three-fold Good oral hygiene can
      prevent death from pneumonia, according to a new study from the US National
      Institute of Dental and Craniofacial Research in Bethesda, Maryland. Pneumonia is
      the leading cause of death in older nursing home residents, and is often
      triggered by aspirating saliva or food. However, analysis of medical records of
      143 older people in a nursing home showed that the help of a certified nursing
      assistant assigned to provide oral hygiene care reduced the risk of dying from
      pneumonia three-fold.

PMID- 27712376
TI  - How apomorphine should be used to treat Parkinson's disease.
AB  - The key clinical features of Parkinson's disease are tremor, rigidity and
      bradykinesia. Oral levodopa is the usual initial treatment but, in advanced
      Parkinson's disease, patients can begin to experience dyskinesias and prolonged
      hypomobility episodes or 'off periods'. Apomorphine is a short-acting dopamine
      receptor agonist that can be used to prevent or reverse 'off period'.

PMID- 27712377
TI  - New NICE bone fracture guidance.
AB  - The National Institute for Health and Clinical Excellence (NICE) has issued final
      guidance on the use of drugs to prevent osteoporotic fractures in postmenopausal
      women. The document details treatment for the prevention of further fractures in
      women who have already had a fracture (secondary prevention). However, for the
      first time it also recommends drugs to help prevent a first fracture due to
      osteoporosis (primary prevention).

PMID- 27712378
TI  - Taiwan.

PMID- 27712379
TI  - Adverse effects of medication for schizophrenia.
AB  - Numbers of older people with schizophrenia are likely to increase with the ageing
      population and they require special attention when considering care and
      treatment. Medication is the mainstay of treatment for patients with
      schizophrenia, to control hallucinations and delusions. Older people are more
      prone to the adverse effects of antipsychotic medication, particularly torso
      movements and buccal twitches. They are also more likely to be prescribed
      inappropriate doses and types of medication. Where drugs are required, smaller
      doses should be prescribed.

PMID- 27712380
TI  - Australia.
AB  - Mental health and healthy ageing; first 24-hour care service for older Aboriginal
      people Older people with more sound mental health are less likely to fall
      according to new research from The Australian National University (ANU). The team
      assessed 787 adults, with an average age of 78, three times over eight years on
      measures of wellbeing, including depressive symptoms, morale and sense of control
      over their lives. The study found that there was a rising fall rate over time
      among those who reported an increase in depressive symptoms or reduction in
      morale during the course of the study.

PMID- 27712382
TI  - Dorset wellbeing project extended.
AB  - A project to promote the wellbeing of older people by bringing local health and
      social care services together has been extended due to its success.

PMID- 27712381
TI  - Canada.
AB  - A journalist facing a life- threatening aneurism has compiled a series of essays
      documenting the most pressing policy implications of our ageing in societies
      around the worl++d as part of a public policy fellowship.

PMID- 27712383
TI  - ?
AB  - Tai chi improves confidence and reduces the risk of falling among at-risk elderly
      people, a small trial has shown. Almost three quarters of patients who attended a
      course of tai chi run by the Heart of Birmingham Primary Care Trust, said their
      confidence had risen.

PMID- 27712384
TI  - Medical and environmental factors play part in falls in hospital.
AB  - Tackling the medical causes and environmental factors that could lead to a
      patient falling are the best ways to limit falls in a hospital setting, according
      to the National Patient Safety Agency (NPSA).

PMID- 27712386
TI  - And in other news.
AB  - You never see TV advertisements about dementia care services, perhaps because
      there are more buyers than sellers, and providers have all the business they can
      cope with. But Bupa has changed that with an ad that it claims is the first one
      ever on offering care for people with dementia.

PMID- 27712385
TI  - Act now, save later.
AB  - The second interim report evaluating 29 local authority-led pilot schemes, known
      as POPPs (Partnerships for Older People Projects), presents encouraging news on
      their performance ( PSSRU 2008 ). These projects have been established for two
      years with funding from the Department of Health. The first phase - 19 projects -
      started in 2006, with the remainder a year later.

PMID- 27712387
TI  - Bakewell can't shake off 'crumpet' epithet.
AB  - The temptation was just too great and most newspapers succumbed. The phrase was
      first used back in the days when objectifying women was as commonplace as
      miniskirts and moptops, but that did not deter reporters from resurrecting it 40
      years later.

PMID- 27712388
TI  - Hospitals need a dedicated team.
AB  - All hospitals should have a dedicated team working to reduce patient falls and
      falls training should be compulsory for staff across all wards, a leading nurse
      consultant has claimed.

PMID- 27712390
TI  - If nurses feel they are poorly treated by management it affects care.
AB  - This study found that nurses' time pressure and their perceptions of unfair
      management contribute to the prevalence of anti-anxiety or hypnotic drug use and
      pressure ulcers, even when controlling for nurse staffing levels. Where employees
      perceive that they are being treated unfairly there is reduced commitment and
      lack of involvement as well as increased staff health problems. Nurses'
      perception of unfairness may reflect a failure to engage nurses in decisions
      about use of anti-anxiety or hypnotic drugs and an under-use of nurses' expertise
      on the daily care needs of residents. Long-term care units should review work
      loads and management practices to support effective communication and
      collaboration among nursing staff.

PMID- 27712389
TI  - Study suggests geriatric patients should have pulse oximetry at night.
AB  - Older people have lower oxygen retention in the supine position during sleep.
      This is due to age-related reduced lung elasticity as well as cardiac, lung or
      brain disease.

PMID- 27712391
TI  - Dementia can affect an individual's personhood.
AB  - This article defines three levels of personhood: ? Biological personhood: Central
      to biological system is sentience or the ability to experience pleasure or pain.
      There is little disagreement that all individuals living with dementia retain
      personhood at a basic biological level. ? Individual personhood: This relates to
      an individual's characteristics including such things as the past, roles,
      personality, values, self-worth and spirituality. ? Sociological personhood: This
      is defined by the perceptions of society and other people's approach to the
      person with dementia. As social contacts become aware of cognitive decline, their
      behaviour towards the individual begins to change. Residents become more isolated
      and sociological personhood is threatened. Individuals living in nursing homes
      can become increasingly socially isolated.

PMID- 27712392
TI  - Exercise and weight loss are key to treating osteoarthritis.
AB  - Osteoarthritis is the most common joint disease and a leading cause of pain and
      disability in older people. Joint replacement for osteoarthritis of the hip is
      the only intervention with a large effect, but is only appropriate for patients
      with advanced disease. There is evidence that topical application of non
      steroidal anti-inflammatory drugs (NSAIDs) is helpful. Although less effective in
      pain relief, oral paracetamol should be tried before oral NSAIDs as it has a
      lower risk of side effects. Some long-used treatments, such as arthroscopic
      debridement and glucosamine, are now thought to be ineffective.

PMID- 27712393
TI  - A whole-systems approach for dementia careDrawing on his 30 years' experience as
      a nurse, Trevor Adams has written a book on dementia care nursing. Here, he
      refers to its contents to explain why nurses should look beyond person-centred
      and relationship-centred care to consider wider social, psychological and
      biological systems that help construct a more rounded picture of the needs of
      people with dementia.
AB  - The nursing care of people with dementia is carried out mainly by general and
      mental health nurses, and takes place in a wide variety of settings such as
      accident and emergency units, orthopaedic wards, people's homes, long- stay wards
      and day hospitals ( care Services Improvement Partnership (CSIP) 2005 ). My own
      experience of nursing people with dementia is as a mental health nurse, but my
      mother developed dementia and this has enabled me to see dementia care nursing
      from a different angle.

PMID- 27712395
TI  - Age no indicator of cancer survival.
AB  - Age is not a key factor in cancer survival, according to a team of researchers in
      Spain. And although 60 per cent of cancers occur in patients over 65, most
      clinical trials still exclude older people. This makes it difficult to predict
      how older people will respond to new cancer treatments.

PMID- 27712394
TI  - The right place to die.
AB  - The government's end-of-life care strategy aims to help people have a dignified
      death in the place of their choosing. For many people this means dying in the
      place where they have lived - at home. 'Is It That Time Already?', a new report
      by Housing 21, the older people's housing and care organisation, and the National
      End-of-Life Care programme, suggests that older people who live in extra care
      housing may be denied this choice because extra care housing is not recognised as
      a 'home for life'.

PMID- 27712396
TI  - First TV ad for dementia care.
AB  - Last month, viewers saw the first-ever TV advertisement about providing care for
      people with dementia. Screened as part of Bupa's initiative, bringing the issue
      of dementia care 'out of the shadows,' the ad features Ernie visiting his sister
      June, who has dementia, in a Bupa care home and shows the personalised care being
      delivered by specially trained staff.

PMID- 27712398
TI  - Nurses address winter's effect on ill health.
AB  - Nurses in the West Midlands have developed an award-winning scheme which aims to
      combat the effects of cold, damp weather on ill health. They identify patients
      whose health could be worsened by poor heating conditions, for example, those
      with asthma, angina, osteoporosis, or those recovering from surgery, and help
      them access grants and other funds to pay for heating and insulation
      improvements.

PMID- 27712397
TI  - ?
AB  - Joan Parsonage (left) will be sending out 27,000 Christmas cards this year.
      That's because the 83-year-old resident of a Bupa nursing home in Wilmslow,
      Cheshire, has had her festive design (inset) chosen from 200 entries to be the
      company's Christmas card for 2008. Joan has enjoyed painting from an early age
      and runs a weekly art class for other residents at the home. Bupa is the largest
      operator of care homes for older people in the UK and runs 304 nursing and
      residential homes with more than 21,000 registered beds - more than 25 per cent
      of which are registered for specialist dementia care.

PMID- 27712401
TI  - Longitudinal quantitative research designs.
AB  - In this paper I aim to present some of the advantages and problems associated
      with longitudinal quantitative research designs. The main feature of longitudinal
      designs is that the effect of time on the subjects of the research can be studied
      better than in cross-sectional designs where several groups (called cohorts), or
      one cohort divided up on the basis of a feature such as age, may be required. If
      you compare two groups on the basis of age you cannot assume that any differences
      you observe are due to age - this is known as the cohort effect. However,
      longitudinal designs bring some problems in terms of keeping subjects in the
      study and the longer the time between points at which stages of the study are
      carried out, the greater the difficulty in retaining subjects. In addition to
      these general features of longitudinal quantitative research designs, some
      specific designs and methods of statistical analysis will be considered.

PMID- 27712403
TI  - Editorial.
AB  - Writing for publication can be a tricky business. Finding the time, finding the
      words, submitting your work to be disfigured by the sharp red pens of reviewers
      and editors, and doing a day job at the same time, can conspire to deter even the
      most motivated and diligent potential author. However, and at risk of boring you
      on a topic that has probably been done to death, writing for publication is an
      important issue. Especially for researchers. So important in fact, that at the
      Workgroup of European Nurse Researchers (WENR) conference in Helsinki earlier in
      July scientific writing featured heavily in workshops and symposia.

PMID- 27712399
TI  - Priming Equine Bone Marrow-Derived Mesenchymal Stem Cells with Proinflammatory
      Cytokines: Implications in Immunomodulation-Immunogenicity Balance, Cell
      Viability, and Differentiation Potential.
AB  - Mesenchymal stem cells (MSCs) have a great potential for treating equine
      musculoskeletal injuries. Although their mechanisms of action are not completely
      known, their immunomodulatory properties appear to be key in their functions. The
      expression of immunoregulatory molecules by MSCs is regulated by proinflammatory
      cytokines; so inflammatory priming of MSCs might improve their therapeutic
      potential. However, inflammatory environment could also increase MSC
      immunogenicity and decrease MSC viability and differentiation capacity. The aim
      of this study was to assess the effect of cytokine priming on equine bone marrow
      derived MSC (eBM-MSC) immunoregulation, immunogenicity, viability, and
      differentiation potential, to enhance MSC immunoregulatory properties, without
      impairing their immune-evasive status, viability, and plasticity. Equine BM-MSCs
      (n = 4) were exposed to 5 ng/mL of TNFalpha and IFNgamma for 12 h (CK5-priming).
      Subsequently, expression of genes coding for immunomodulatory, immunogenic, and
      apoptosis-related molecules was analyzed by real-time quantitative polymerase
      chain reaction. Chromatin integrity and proliferation assays were assessed to
      evaluate cell viability. Trilineage differentiation was evaluated by specific
      staining and gene expression. Cells were reseeded in a basal medium for
      additional 7 days post-CK5 to elucidate if priming-induced changes were
      maintained along the time. CK5-priming led to an upregulation of immunoregulatory
      genes IDO, iNOS, IL-6, COX-2, and VCAM-1. MHC-II and CD40 were also upregulated,
      but no change in other costimulatory molecules was observed. These changes were
      not maintained 7 days after CK5-priming. Viability and differentiation potential
      were maintained after CK5-priming. These findings suggest that CK5-priming of eBM
      MSCs could improve their in vivo effectiveness without affecting other eBM-MSC
      properties.

PMID- 27712400
TI  - Visual and audio emotion processing training for outpatients with schizophrenia:
      an integrated multisensory approach.
AB  - Deficits in emotion processing (EP) represent a target of rehabilitation in
      schizophrenia, as they have been related to poor personal and social functioning.
      To date neither the relationship between these deficits and the generalised
      cognitive impairment, nor the involvement of specific mechanisms of perception
      (visual or auditory) are fully comprehended. We developed two treatments
      targeting EP, through visual or auditory channels, with the aim of disentangling
      possible differences and/or interactions between the two modalities in
      schizophrenia-related impairments, also taking into account the role of cognition
      and social functioning. Thirty five outpatients with schizophrenia were assessed
      for neurocognition, social functioning and EP (visual and auditory channel) and
      participated in either visual or auditory EP training or in an active control
      group. Results showed a significant improvement in EP through the specific
      channel trained for both groups, with an extended effect also on vocal stimuli
      for the visual training group. Positive correlations were found between working
      memory, social functioning and EP. Our findings help to shed light on the
      possible different involvement of perceptual channels in schizophrenia, as well
      as supporting previous evidence that emotion recognition may be inter-related but
      does not overlap with neurocognition and can be specifically trained.

PMID- 27712404
TI  - The crossover study design and its clinical application.
AB  - This paper describes the crossover design in research methodology and illustrates
      its use in a clinical study in an intensive care unit (ICU). The benefits and
      shortcomings of the design are described. Strategies to avoid or minimise the
      shortcomings are explained with reference to examples from a study carried out in
      clinical practice. By linking theory to practice in this way, we hope to help to
      increase the understanding of this methodology for the nurse researcher.

PMID- 27712405
TI  - Introducing single case study research design: an overview.
AB  - An overview of case study research The use of case study design in research has a
      long and distinguished history in many disciplines ( 1 ). It is used in law,
      education, history, medicine, psychology and business ( 2 ). Yin ( 3 ) stated
      that case studies are essential for social science and that they are used
      extensively in practice-oriented professions. Examples of studies include those
      of Freud, from which he derived his theories of personality ( 4 ), and Whyte's
      study of neighbourhood gangs in Chicago ( 5 ), which was found by other
      researchers ( 6 ) to be a typical case and again, as in the example of Freud, led
      to the development of theory. The term 'case study' refers to both a process of
      inquiry - that is, studying a case or designing and executing a case study - and
      its end product, the case study or 'case report' ( 7 ).

PMID- 27712406
TI  - Single case experimental design: controlling the study.
AB  - Single case reports are popular in nursing, as well as, for example, in
      education, psychology and medicine, and can give a clear picture of aspects of
      individual characteristics in a way that neither large scale controlled trials
      nor even large scale qualitative studies can hope to do. In both these latter
      cases, considerable individual detail is lost, owing to the need to present what
      is essentially a precis of these characteristics in the final published report.

PMID- 27712407
TI  - Linking philosophy and method in the research process: the case for realism.
AB  - The early stages of a research study involve much thought, reflection and
      planning. A clear understanding of the philosophical basis of the research
      strategy is important for a number of reasons. It helps to clarify research
      design; enables recognition of whether the strategy will or will not work; helps
      to identify and create designs beyond past experience ( 1 ); helps to ensure
      consistency in the application of different methods to a research question; and
      provides grounding for research methods within an accepted epistemological
      paradigm. This differentiates academic work from lay knowledge, by increasing its
      validity ( 2 ).

PMID- 27712408
TI  - Dilemmas of interviewing women who have given birth in Pakistan.
AB  - This paper focuses upon dilemmas that arose when Pakistani women were interviewed
      about their birth experiences in Pakistan. The dilemmas are grounded in issues
      from my own background and research stance and the methodology used. These
      factors expose issues from my white Western heritage and entry to the research
      field, as well as dilemmas ranging from power within the method to the
      sensitivity around the role and accountability of the interviewer. The over
      arching dilemma involves the heavy weight of responsibility incumbent upon me to
      interpret the women's words accurately and leave them unharmed by the experience
      of being interviewed.

PMID- 27712409
TI  - Anisotropic Shape-Memory Alginate Scaffolds Functionalized with Either Type I or
      Type II Collagen for Cartilage Tissue Engineering.
AB  - Regenerating articular cartilage and fibrocartilaginous tissue such as the
      meniscus is still a challenge in orthopedic medicine. While a range of different
      scaffolds have been developed for joint repair, none have facilitated the
      development of a tissue that mimics the complexity of soft tissues such as
      articular cartilage. Furthermore, many of these scaffolds are not designed to
      function in mechanically challenging joint environments. The overall goal of this
      study was to develop a porous, biomimetic, shape-memory alginate scaffold for
      directing cartilage regeneration. To this end, a scaffold was designed with
      architectural cues to guide cellular and neo-tissue alignment, which was
      additionally functionalized with a range of extracellular matrix cues to direct
      stem cell differentiation toward the chondrogenic lineage. Shape-memory
      properties were introduced by covalent cross-linking alginate using carbodiimide
      chemistry, while the architecture of the scaffold was modified using a
      directional freezing technique. Introducing such an aligned pore structure was
      found to improve the mechanical properties of the scaffold, and promoted higher
      levels of sulfated glycosaminoglycans (sGAG) and collagen deposition compared to
      an isotropic (nonaligned) pore geometry when seeded with adult human stem cells.
      Functionalization with collagen improved stem cell recruitment into the scaffold
      and facilitated more homogenous cartilage tissue deposition throughout the
      construct. Incorporating type II collagen into the scaffolds led to greater cell
      proliferation, higher sGAG and collagen accumulation, and the development of a
      stiffer tissue compared to scaffolds functionalized with type I collagen. The
      results of this study demonstrate how both scaffold architecture and composition
      can be tailored in a shape-memory alginate scaffold to direct stem cell
      differentiation and support the development of complex cartilaginous tissues.

PMID- 27712411
TI  - A sideways look at images of age.

PMID- 27712410
TI  - Makeover brings new look and added value.
AB  - Welcome to the new-look Nursing Older People. Over the summer we have given the
      journal a complete makeover. We have put on a little weight - an extra eight
      pages this month - and we have a bright, new design. The restructured sections
      should help you to find what you want more easily and, responding to the
      extensive feedback you have given us, the content is better than ever.

PMID- 27712412
TI  - Bandolier.
AB  - Many nurses will be familiar with Bandolier, originally conceived by Oxford-based
      scientists as an independent journal on evidence-based health care. Its online
      version claims a million visitors each month.

PMID- 27712413
TI  - Older people confused by complex public services, say MPs.
AB  - Public services for the UK's 10.5 million older people are poorly co-ordinated
      and confusing for those who use them, MPs have said.

PMID- 27712414
TI  - ?
AB  - A free festival of music, entertainment and dance for older people and their
      friends and relatives was staged in London last month and featured the UK's
      oldest established steel band, Nostalgia, greatest hits from the tribute band
      Buddy Holly & The Cricketers, and dance and movement from the Lilian Baylis over
      60s Performance Group. The Capital Age Festival, now in its second year, also
      featured Cruel Sea, a film installation project that explored the experience of
      Merchant Navy veterans from across the Commonwealth who served in the Second
      World War.

PMID- 27712416
TI  - A good read.
AB  - Actively ageing magazines are a publishing hit. Magazines specifically directed
      at older people, such as The Oldie, Choice, Saga and Yours, have achieved success
      at the national level. Actively ageing is the market with potential these days.
      This year, three magazines for the over-55s have appeared as part of that other
      publishing phenomenon, the county magazines. 'The idea is to produce a good,
      reader-based magazine,' says Paul Hazeldine, editor of Our Time Staffordshire.
      'We want to get reaction and participation from readers, so they make the
      magazine part of their life.'

PMID- 27712417
TI  - Dynamic role boundaries in intermediate care services.
AB  - The rapid growth and development of intermediate care services for older people
      has led to wide variations in service delivery and istaffing arrangements. This
      paper reports an exploratory investigation which used a case study approach to
      examine two services run by one primary care trust. One focused on admission
      avoidance (Rapid Response), while the other supported discharges from
      institutional care (Hospital at Home). Even though both services were labelled as
      'intermediate care', they were different in almost every major aspect of service
      organisation and delivery. Nurses and therapists working with the rapid response
      team felt that there was little role overlap, while the longer term nature of
      hospital at home provided more scope for it. The researchers conclude that role
      overlap can benefit all concerned.

PMID- 27712422
TI  - ?
AB  - Four veterans of the First World War laid wreaths at the Cenotaph in London last
      month to commemorate the 90th anniversary of war being declared against Germany
      in 1914. All four are aged over 100 and as well as laying wreaths they read
      prayers and poems in memory of fallen comrades.

PMID- 27712424
TI  - Trailblazing in the Fens.

PMID- 27712423
TI  - Perceived health promotion practice by older women: use of herbal products.
AB  - There is some evidence that women are more likely than men to use complementary
      health products for chronic conditions at some point in their lives. This study
      conducted in Florida built upon an earlier one by the same authors to follow up
      subjects after an interval of 18 months. There were 70 women aged 65 and over in
      the sample. Instruments employed included the Multidimensional Health Locus of
      Control Scale, and the Perceived Health Competence Scale. The study revealed that
      the prevalence of herbal product usage and the number of products used remained
      the same over the 18-month period. Differences in locus of control between users
      and non-users were not statistically significant.

PMID- 27712425
TI  - New scheme offers protection to vulnerable older people.
AB  - A scheme to protect older people and other vulnerable adults from abuse has been
      formally launched by ministers.

PMID- 27712426
TI  - The antimicrobial activity ofmaggots: in-vivo results.
AB  - This Dutch study reports the results of using maggots to treat Gram-positive and
      Gramnegative infected wounds in 16 patients, half of whom had suffered trauma.
      The authors stress the limitations of this trial as it was an open label, non
      comparative cohort study in design, and all patients with a severe wound
      infection were treated with antibiotics. However, even though no definite
      conclusions regarding the effectiveness of maggot therapy could be drawn, useful
      pointers for clinical practice were reported. The mean treatment time was found
      to be 27 days, with a range of 11 to 83 days, and with the maggots being changed
      an average of seven times. Maggot therapy was found to be more effective in Gram
      positive wounds. The authors conclude by discussing what is known about the
      mechanisms through which maggots affect wounds.

PMID- 27712427
TI  - An exploration of nutrition and eating disabilities in relation to quality of
      life at 6 months post-stroke.
AB  - This study carried out in south London involved interviews with 206 patients who
      had been hospitalised by a stroke. The mean age of participants was 71 years.
      Interviews were conducted in stroke survivors' homes by a single researcher, and
      a range of tools were used. The results indicated that mood was a major factor in
      poor nutritional status. In addition, social support, eating-related disabilities
      and age were found to have a significant impact.

PMID- 27712429
TI  - ?
AB  - Mixed methodologies were employed in this study of hope-fostering strategies. The
      sample of ten older people, drawn from Canadian rural prairie communities, was
      arrived at through theoretical purposive sampling. The data collection
      instruments employed were the Herth Hope Index and the Edmonton Symptom
      Assessment Scale. The interviews revealed a range of hopefostering strategies,
      including 'leaving a legacy', 'short term goals', 'faith', and 'symbols of hope'.
      As one participant said, 'These robins, they hop along, and they sing to me, they
      say "cheer up, cheer up".' The authors discuss their findings in the light of
      previous studies of hope-fostering strategies.

PMID- 27712430
TI  - Lessons learned from NHS leadership programme.
AB  - A booklet designed to show how modern matrons and consultant nurses working with
      older people can benefit from leadership training has been published by the NHS
      Leadership Centre.

PMID- 27712431
TI  - Older people living in nursing homes or other community care facilities:
      registered nurses' views of their working situation and co-operation with family
      members.
AB  - This Swedish study used a questionnaire to survey the opinions of registered
      nurses working with older people in a variety of community settings. Almost half
      the nurses were not satisfied with their working conditions, with increasing
      demand and limited resources being major factors. Female nurses were more likely
      than their male colleagues to believe that family members were a resource in
      caring for older people.

PMID- 27712434
TI  - Donald L. Burnham: At the Helm in Stormy Seas.

PMID- 27712435
TI  - Conferences.
AB  - Topics addressed include the value of eprescribing and ebooking, engaging
      clinicians in the national programme for information technology (NPfIT), legal
      issues relating to ehealth, local implementation challenges for NHS trusts and
      primary care trusts, and the direction of technological development.

PMID- 27712436
TI  - Networking ideas.
AB  - Nurses meanwhile have a chance to share their innovative ideas online through a
      new forum. Healthcare research charity Picker Institute Europe wants nurses to
      post suggestions for improving patients' experiences of care on a 'good practice
      network', which is expected to build into a searchable database of real life
      cases.

PMID- 27712432
TI  - A chemical stability study of trimethylsilane plasma nanocoatings for coronary
      stents.
AB  - Trimethylsilane (TMS) plasma nanocoatings were deposited onto stainless steel
      coupons in direct current (DC) and radio frequency (RF) glow discharges and
      additional NH3/O2 plasma treatment to tailor the coating surface properties. The
      chemical stability of the nanocoatings were evaluated after 12 week storage under
      dry condition (25  degrees C) and immersion in simulated body fluid (SBF) at 37 
      degrees C. It was found that nanocoatings did not impact surface roughness of
      underlying stainless steel substrates. X-ray photoelectron spectroscopy and
      Fourier transform infrared spectroscopy were used to characterize surface
      chemistry and compositions. Both DC and RF nanocoatings had Si- and C-rich
      composition; and the O- and N-contents on the surfaces were substantially
      increased after NH3/O2 plasma treatment. Contact angle measurements showed that
      DC-TMS nanocoating with NH3/O2 treatment generated very hydrophilic surfaces. DC
      TMS nanocoatings with NH3/O2 treatment showed minimal surface chemistry change
      after 12 week immersion in SBF. However, nitrogen functionalities on RF-TMS
      coating with NH3/O2 post treatment were not as stable as in DC case. Cell culture
      studies revealed that the surfaces with DC coating and NH3/O2 post treatment
      demonstrated substantially improved proliferation of endothelial cells over the
      12 week storage period at both dry and wet conditions, as compared to other
      coated surfaces. Therefore, DC nanocoatings with NH3/O2 post treatment may be
      chemically stable for long-term properties, including shelf-life storage and
      exposure to the bloodstream for coronary stent applications.

PMID- 27712437
TI  - Intensive care.
AB  - The families and friends of patients in intensive care are the target of a new
      website at www.ics.ac.uk It provides easily accessible answers to common
      questions away from stressful hospital situations.

PMID- 27712439
TI  - Relocation guide.
AB  - Moving home this autumn? If so, and if you want to take some of the stress out of
      the process, the website for you could be www.nhsconsortium.com It is designed
      specifically for NHS staff who are relocating, and provides access to discounted
      services and offers help in finding solicitors and general advice on what is
      involved in buying a new home.

PMID- 27712441
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27712440
TI  - Vantage point.
AB  - Let's face it, some nurses shouldn't be in nursing. We know who they are but
      dealing with them can be extraordinarily difficult.

PMID- 27712442
TI  - Jan grant.
AB  - What are your most important roles? First, developing clinical leadership across
      all levels and ensuring that we, as senior NHS managers, develop and secure
      leaders for the future.

PMID- 27712443
TI  - ?

PMID- 27712444
TI  - Childhood vaccination.
AB  - Information on childhood vaccines in Scotland is available on a new website. The
      site contains publications relating to vaccines being introduced and provides
      detailed information on all those that are recommended in the national
      immunisation programme.

PMID- 27712445
TI  - Nursing director helps close public 'reality gap'.
AB  - Director of quality and nursing Claire Old is among the healthcare professionals
      who want to change public perception about the number of managers in the NHS.

PMID- 27712446
TI  - Booking staff online.
AB  - For those still using agency nurses and midwives, online booking could become a
      convenient option if a new website is successful, writes Steven Black. Newcross
      Healthcare Solutions, a company that provides temporary staffing solutions for
      NHS trusts and private hospitals, and for public and private care homes, has
      launched a UK wide online booking system.

PMID- 27712447
TI  - Matron 'charter' to spell out cleaning authority.
AB  - Modern matrons can expect the publication this month of a cleaning 'charter'
      spelling out their authority and duties in helping to tackle healthcare acquired
      infections.

PMID- 27712449
TI  - The new register.
AB  - The new Nursing and Midwifery Council register for nurses, midwives and
      specialist community practitioners is also available online for the public and
      professionals at www.nmc-uk.org.

PMID- 27712448
TI  - Two-year funding to train more leaders.
AB  - The RCN is bolstering its leadership team in Scotland after receiving government
      funding worth L500,000 to develop its training schemes for two more years.

PMID- 27712450
TI  - New CNO priorities.
AB  - Leadership was among the nursing priorities outlined by Scotland's new chief
      nursing officer Paul Martin (pictured) at his first official engagement.

PMID- 27712452
TI  - ?
AB  - In the current political climate, it's refreshing to be able to welcome an idea
      from across the Atlantic. October is Black History Month, an initiative started
      by the son of former slaves who himself worked as a child labourer in Kentucky
      coal mines. Later, while studying for a PhD at Harvard University, he lamented
      the lack of reference to black people except by negative stereotyping.

PMID- 27712451
TI  - Regulation rethink.
AB  - The Health Professions Council, the regulatory body for allied health
      professionals from chiropodists to physiotherapists, has announced changes to its
      online systems.

PMID- 27712454
TI  - The Action Level.

PMID- 27712453
TI  - ?
AB  - Putting their heads together: the Department of Health last month published the
      long awaited National Service Framework for Children, Young People and Maternity
      Services. Health secretary John Reid said it was 'the biggest national effort
      there has ever been to improve health and social care services for children,
      young people and their parents'.

PMID- 27712455
TI  - Independent Component Decomposition of Human Somatosensory Evoked Potentials
      Recorded by Micro-Electrocorticography.
AB  - High-density surface microelectrodes for electrocorticography (ECoG) have become
      more common in recent years for recording electrical signals from the cortex.
      With an acceptable invasiveness/signal fidelity trade-off and high spatial
      resolution, micro-ECoG is a promising tool to resolve fine task-related spatial
      temporal dynamics. However, volume conduction - not a negligible phenomenon - is
      likely to frustrate efforts to obtain reliable and resolved signals from a sub
      millimeter electrode array. To address this issue, we performed an independent
      component analysis (ICA) on micro-ECoG recordings of somatosensory-evoked
      potentials (SEPs) elicited by median nerve stimulation in three human patients
      undergoing brain surgery for tumor resection. Using well-described cortical
      responses in SEPs, we were able to validate our results showing that the array
      could segregate different functional units possessing unique, highly localized
      spatial distributions. The representation of signals through the root-mean-square
      (rms) maps and the signal-to-noise ratio (SNR) analysis emphasizes the advantages
      of adopting a source analysis approach on micro-ECoG recordings in order to
      obtain a clear picture of cortical activity. The implications are twofold: while
      on one side ICA may be used as a spatial-temporal filter extracting micro-signal
      components relevant to tasks for brain-computer interface (BCI) applications, it
      could also be adopted to accurately identify the sites of nonfunctional regions
      for clinical purposes.

PMID- 27712457
TI  - Do we understand pain from a biopsychosocial perspective? A review and discussion
      of the usefulness of some pain terms.
AB  - Pain is a biopsychosocial phenomenon and should be assessed and managed from this
      perspective. However, the dualistic mind-body perspective is still present and
      affects the way this health situation is addressed. Following this approach, pain
      can either be attributed to an identifiable cause or considered as
      'psychological' pain, for which there is neither an identifiable cause nor
      adequate treatment. Faced with this situation, first, we introduce some concepts
      that have been used (and are still frequently being used) to refer to pain with
      no identifiable cause. Next, we question the usefulness of these 'dualistic
      terms' and, finally, defend the biopsychosocial perspective to advance in the
      conceptualization of pain and avoid using terms that can foster a dualistic
      perspective.

PMID- 27712456
TI  - Emergence of Narrowband High Frequency Oscillations from Asynchronous, Uncoupled
      Neural Firing.
AB  - Previous experimental studies have demonstrated the emergence of narrowband local
      field potential oscillations during epileptic seizures in which the underlying
      neural activity appears to be completely asynchronous. We derive a mathematical
      model explaining how this counterintuitive phenomenon may occur, showing that a
      population of independent, completely asynchronous neurons may produce narrowband
      oscillations if each neuron fires quasi-periodically, without requiring any
      intrinsic oscillatory cells or feedback inhibition. This quasi-periodicity can
      occur through cells with similar frequency-current ([Formula: see text]-[Formula:
      see text]) curves receiving a similar, high amount of uncorrelated synaptic
      noise. Thus, this source of oscillatory behavior is distinct from the usual cases
      (pacemaker cells entraining a network, or oscillations being an inherent property
      of the network structure), as it requires no oscillatory drive nor any specific
      network or cellular properties other than cells that repetitively fire with
      continual stimulus. We also deduce bounds on the degree of variability in neural
      spike-timing which will permit the emergence of such oscillations, both for
      action potential- and postsynaptic potential-dominated LFPs. These results
      suggest that even an uncoupled network may generate collective rhythms, implying
      that the breakdown of inhibition and high synaptic input often observed during
      epileptic seizures may generate narrowband oscillations. We propose that this
      mechanism may explain why so many disparate epileptic and normal brain mechanisms
      can produce similar high frequency oscillations.

PMID- 27712458
TI  - Acceptability of a brief computerized intervention targeting anxiety sensitivity.
AB  - Despite the well-documented efficacy of cognitive behavioral treatments for
      anxiety disorders, the acceptability of these treatments remains an under
      researched area. A better understanding of acceptability could help to improve
      the initiation of, and engagement in, these effective interventions. Recent
      research has suggested computerized interventions of anxiety-related risk factors
      may be one way to improve acceptability and overcome several common barriers to
      treatment. Considering this, the current study tested the acceptability of a
      computerized, anxiety sensitivity (AS)-focused treatment among a sample of
      treatment-seeking community participants and military veterans (N = 58). Results
      indicated that the majority of participants rated the intervention as acceptable,
      and that drop-out rate was low (ie 5%). Moreover, higher acceptability scores
      were associated with older age, veteran status, lower income levels, African
      American race, and being separated/divorced. Findings suggest that a computerized
      AS-focused treatment may be an acceptable treatment method, and may have
      advantages in acceptability for hard to reach populations.

PMID- 27712461
TI  - Oral Health-Related Quality of Life Before and After Treatment of Dentin
      Hypersensitivity With Cyanoacrylate and Laser.
AB  - BACKGROUND: The aim of this longitudinal study is to verify changes in the oral
      health-related quality of life of patients 180 days after treatment of dentin
      hypersensitivity (DH) with laser and cyanoacrylate. METHODS: This clinical,
      controlled, randomized, double-masked trial used a split-mouth design, and
      quadrants were randomized to receive either laser or cyanoacrylate treatments.
      All patients received both treatments. The study included 62 patients aged 12 to
      60 years (mean: 31.4 years) in whom a total of 432 teeth were treated. Quadrants
      were randomly distributed into two groups: cyanoacrylate (n = 218 teeth) or laser
      (n = 216 teeth) treatment. DH was evaluated with air and cold stimuli at 24
      hours, 30, 90, and 180 days after treatment. The Oral Health Impact Profile (OHIP
      14) questionnaire was applied at baseline and 180 days after treatment. RESULTS:
      There were statistically significant differences in the following OHIP-14
      subscales before and after treatment: physical pain (P = 0.002), psychologic
      discomfort (P <0.001), psychologic disability (P = 0.003), social disability (P =
      0.01), and total score (P <0.001). At the end of the study, 80.6% of participants
      reported an improvement in their condition. CONCLUSION: There was a reduction in
      the impact of DH on the quality of life of study participants after interventions
      with laser and cyanoacrylate.

PMID- 27712462
TI  - Mandibular Degree II Furcation Defects Treatment With Platelet-Rich Fibrin and 1%
      Alendronate Gel Combination: A Randomized Controlled Clinical Trial.
AB  - BACKGROUND: Different materials have been investigated for renewal of lost
      supporting periodontal structures and tested for furcation defect treatment.
      Platelet-rich fibrin (PRF) is a pool of growth-promoting factors and cytokines
      that promote bone regeneration and maturation of soft tissue. Alendronate (ALN),
      an influential member of the bisphosphonate group, is known to enhance
      osteoblastogenesis and inhibit osteoclastic bone resorption, thus promoting
      tissue regeneration. This randomized trial was done to assess effectiveness of
      PRF and 1% ALN gel combination in mandibular degree II furcation defect treatment
      in comparison with PRF and access therapy alone. METHODS: Seventy-two mandibular
      molar furcation defects were treated with either access therapy alone (group 1),
      access therapy with PRF (group 2), or access therapy with PRF and 1% ALN (group
      3). Plaque index, modified sulcus bleeding index, probing depth (PD), relative
      vertical attachment level (RVAL) and relative horizontal attachment level (RHAL),
      and intrabony defect depth were recorded at baseline and 9 months
      postoperatively. Radiographically, defect fill, assessed in percentage, was
      evaluated at baseline, before surgery, and 9 months post-therapy. RESULTS: Group
      3 showed greater PD reduction and RVAL and RHAL gain when compared with groups 1
      and 2 postoperatively. Moreover, group 3 sites showed a significantly greater
      percentage of radiographic defect fill (56.01% +/- 2.64%) when compared with
      group 2 (49.43% +/- 3.70%) and group 1 (10.25% +/- 3.66%) at 9 months.
      CONCLUSIONS: Furcation defect treatment with autologous PRF combined with 1% ALN
      gel results in significant therapeutic outcomes when compared with PRF and access
      therapy alone. Combining ALN with PRF has potential for regeneration of furcation
      defects without any adverse effect on healing process.

PMID- 27712463
TI  - Peptide 19 of Porphyromonas gingivalis Heat Shock Protein Is a Potent Inducer of
      Low-Density Lipoprotein Oxidation.
AB  - BACKGROUND: Although periodontal pathogens show a strong association with
      development of atherosclerosis, little is known about how a microorganism
      contributes to disease onset and progression. Oxidation of low-density
      lipoprotein (LDL) is a major risk factor of atherogenesis. The principal
      objective of this study is to evaluate the ability of peptide 19 (Pep19) of
      Porphyromonas gingivalis (Pg) heat shock protein (HSP) as a potent inducer of LDL
      oxidation, and a secondary objective is to compare this ability with that of
      Pep19 from different bacteria. METHODS: HSP60, Pep14, and Pep19 from Pg and THP-1
      monocytes were cultured, and the extent of LDL oxidation induced by each peptide
      was evaluated by an assay for thiobarbituric acid-reactive substances (TBARS).
      Pep19 and HSP60 from Chlamydia pneumoniae and Mycobacterium tuberculosis were
      also cultured with THP-1 monocytes and evaluated by the TBARS assay. After
      incubation of macrophages with LDL and peptides from Pg, Oil Red O staining was
      performed for examination of foam cells, macrophages that took up the oxidized
      LDL. RESULTS: Monocyte-mediated native-LDL oxidation under the influence of Pep19
      or HSP60 from Pg was significantly stronger than oxidation induced by the
      counterpart Pep19 or HSP60 from C. pneumoniae or M. tuberculosis. Pep19 from Pg
      HSP60 showed a stronger ability to induce LDL oxidation than did Pep14 from Pg
      HSP60. CONCLUSION: These results suggest Pep19 from Pg HSP60 has a distinct
      ability to induce native-LDL oxidation as a plausible mechanism by which this
      peptide may drive epitope spreading to the neoantigen, i.e., oxidized LDL, in the
      pathogenesis of atherosclerosis.

PMID- 27712464
TI  - In Vitro Biofilm Formation on Titanium and Zirconia Implant Surfaces.
AB  - BACKGROUND: It has been hypothesized that zirconia might have a reduced bacterial
      adhesion compared with titanium; however, results from experimental studies are
      rather controversial. The aim of the present study is to compare biofilm
      formation on zirconia and titanium implant surfaces using an in vitro three
      species biofilm and human plaque samples. METHODS: Experimental disks made of
      titanium (Ti) or zirconia (ZrO2) with a machined (M) or a sandblasted (SLA) and
      acid-etched (ZLA) surface topography were produced. An in vitro three-species
      biofilm or human plaque samples were applied for bacterial adhesion to each type
      of disk, which after 72 hours of incubation was assessed using an anaerobic flow
      chamber model. RESULTS: Zirconia showed a statistically significant reduction in
      three-species biofilm thickness compared with titanium (ZrO2-M: 8.41 MUm; ZrO2
      ZLA: 17.47 MUm; Ti-M: 13.12 MUm; Ti-SLA: 21.97 MUm); however, no differences were
      found regarding three-species-biofilm mass and metabolism. Human plaque analysis
      showed optical density values of 0.06 and 0.08 for ZrO2-M and ZrO2-ZLA, and
      values of 0.1 and 0.13 for Ti-M and Ti-SLA, respectively; indicating a
      statistically significant reduction in human biofilm mass on zirconia compared
      with titanium. Additionally, zirconia revealed a statistically significant
      reduction in human plaque thickness (ZrO2-M: 9.04 MUm; ZrO2-ZLA: 13.83 MUm; Ti-M:
      13.42 MUm; Ti-SLA: 21.3 MUm) but a similar human plaque metabolism compared with
      titanium. CONCLUSION: Zirconia implant surfaces showed a statistically
      significant reduction in human plaque biofilm formation after 72 hours of
      incubation in an experimental anaerobic flow chamber model compared with titanium
      implant surfaces.

PMID- 27712465
TI  - Antioxidant capacity of (+)-catechin visible-light photoirradiated in the
      presence of vitamin B2.
AB  - OBJECTIVES: Catechins are important components of human diet and have received
      special attention due to their antioxidant capacity. The purpose of this paper
      was to study the antioxidant action of (+)-catechin (CTQ) in the presence of
      vitamin B2 (riboflavin) as light-absorbing agent. Furthermore, two model
      compounds, catechol (CTC) and resorcinol (RSC), were selected in order to
      elucidate the reactive target of the CTQ molecule. The influence of pH-medium was
      investigated. METHODS: Stationary photolysis, polarographic detection of
      dissolved oxygen, reactive oxygen species (ROS)-scavengers, time-resolved near-IR
      phosphorescence detection, stationary, and time-resolved fluorescence and laser
      flash photolysis techniques were employed. RESULTS: CTQ interacts with riboflavin
      under visible-light photoirradiation as well as with different ROS which are
      generated in this mechanism. Radical-scavenging activity increases with
      increasing of pH-medium. DISCUSSION: pH-effect of the medium on radical
      scavenging activity comes from the increased electron-donating ability of CTQ
      upon deprotonation. These results are very interesting due to the fact that the
      pH of the food products displays important variations. The [Formula: see text]
      scavenging ability of CTQ, would be equal to the additive contribution of each
      reactive center, CTC, and RSC, present at the molecule of CTQ. However, CTQ would
      have a moderate ability to removal of [Formula: see text]-species at pH 7.

PMID- 27712468
TI  - Issues in research.
AB  - Much of the following information was provided by the Royal College of Nursing
      Research and Development Co-ordinating Centre. More information can be found on
      www.man.ac.uk/rcn/. For further details contact Dave O'Carroll. Tel: 0161-237
      2171. Fax: 0161-237 2620. E-mail: daveocarroll@man.ac.uk.

PMID- 27712466
TI  - Collaboration or renunciation? The role of traditional medicine in mental health
      care in Rwanda and Eastern Cape Province, South Africa.
AB  - Traditional medicine (TM) and biomedicine represent parallel health systems in
      many developing countries; the latter dominating in public policies, while the
      former still retain considerable influence among the general public. This study
      investigates how mental health care professionals responsible for mental health
      care implementation comprehend and relate to the intersection between TM and
      biomedicine in the cases of Rwanda and the Eastern Cape Province, South Africa.
      The material is based on semi-structured interviews with mental health care
      stakeholders in Eastern Cape, South Africa and Rwanda. The findings confirm an
      impact of TM in the treatment of mental health issues in Rwanda and South Africa
      due to TM being more accessible than biomedical medicine, widespread traditional
      perceptions of mental illness in society, and the lack of knowledge of biomedical
      treatments. Furthermore, the respondents identified three strategies to manage
      the impact of TM; improved accessibility of biomedical facilities, outreach
      education about mental illness, and, in the Eastern Cape case, collaboration
      between traditional healers and biomedicine. The study points to the necessity to
      take TM into consideration as an important component of health systems and
      policies in the Global south.

PMID- 27712469
TI  - Collaboration in research.
AB  - The need for researchers to work closely with people who use health and social
      care services has been a central theme in recent policy developments. Ruth
      Northway and colleagues discuss a participative research project.

PMID- 27712471
TI  - Doing Research Ourselves. A Report of the Strategies for Living. Research Support
      Project Vicky Nicholls Doing Research Ourselves. A Report of the Strategies for
      Living. Research Support Project The Mental Health Foundation No. of pages: 28 1
      90364X 00 X 190364X00X.
AB  - The involvement in research of people who use health and social care services can
      take a variety of different forms. In some instances it will involve the co
      option of service users on to service led research projects, while in others
      service users themselves initiate, control and undertake independent research.
      This document is a report of a project undertaken by the Mental Health
      Foundation, which sought to develop and support the latter approach.

PMID- 27712472
TI  - Performing interprofessional research: the example of a team care project.

PMID- 27712474
TI  - Interprofessional research in clinical practice.
AB  - Interprofessional research involves the collaboration of two or more health
      professionals in the research process, be it setting the research agenda,
      designing or implementing a research study, or evaluating published work. Sarah
      Ryan and Andy Hassell argue that the need for interdisciplinary participation has
      been recognised and endorsed in clinical practice but has yet to impact fully on
      nursing research.

PMID- 27712473
TI  - Interviewing colleagues.
AB  - Qualitative research methods are popular among nurses and an increasing number of
      them are undertaking small-scale qualitative studies in conjunction with practice
      related post -graduate degrees ( Jarvis 2000 ). Phil McEvoy discusses some of the
      issues that may arise when practitioner - researchers conduct conversational
      interviews with colleagues as part of a practice based research project.

PMID- 27712475
TI  - Analysis of phenomenological data.
AB  - Lisa Whiting offers some personal insights into using Giorgi's phenomenological
      method in a small-scale research study.

PMID- 27712476
TI  - Research collaboration.
AB  - Collaborative interdisciplinary research can contribute to bridging the gap
      between research and practice. This paper by Leslie Gelling and Dot Chatfield
      considers the nature of collaborative research, describes three models of
      collaboration and suggests some potential benefits of successful research
      collaboration to individuals, groups, organisations and consumers.

PMID- 27712477
TI  - Editorial.
AB  - It will probably come as no surprise to many readers of Nurse Researcher to hear
      that nurse research in the UK is dramatically under-funded compared to other
      disciplines. According to a newly-published study, the funding available to nurse
      researchers in this country lags far behind that which is available to those
      holding similar posts in countries such as the United States and Canada.

PMID- 27712481
TI  - Viewpoint.

PMID- 27712483
TI  - Families and Mental Illness: Current Interpersonal and Biological Approaches
      (Part 2).

PMID- 27712484
TI  - Specialist nurses for older people.
AB  - The profession needs to identify where specialist nursing expertise fits in In
      the JAN article, Dr Jan Reed Professor of Health Care for Older People at
      Northumbria University, and colleagues argue that the everyday activities of
      specialist nurses for older people seem to be driven by policies, resources and
      the personal characteristics of the individual nurse, rather than ideas of
      universal service user needs or wishes. They struggle to fit existing posts with
      theories about nursing older people, and the implications for education and
      training.

PMID- 27712485
TI  - Ethnic minorities are often under-represented in mental health services.
AB  - Nurses need to be aware that people from ethnic minority groups may need
      particular encouragement to seek help if they develop dementia. A mixed age focus
      group of British people of Punjabi Indian origin was asked to discuss ageing and
      problems of old age. One focus group member said: 'We are afraid to come to
      mental health services because no one will speak our language. It is so difficult
      to express emotional difficulties in another language.'

PMID- 27712486
TI  - Folic acid supplements significantly improve memory function.
AB  - Cognitive function declines with age. Modifiable risk factors have been
      identified and poor folate status is suspected of being one such risk factor.
      This trial compared three years of folic acid supplementation with placebo in
      people, aged 50-70, who had raised blood concentrations of homocysteine
      (associated with atherosclerosis). The findings were that folic acid
      supplementation significantly improved those domains of cognitive function
      (memory and information processing) that tend to decline with age.

PMID- 27712487
TI  - Cognitive impairment may not hamper ability to describe quality of life.
AB  - Subjective accounts of quality of life are vital if we are to better understand
      the experience of people with dementia; however, cognitive limitations and lack
      of insight have been seen as barriers to self-reporting in quality of life
      assessment. Nevertheless, it has been suggested that awareness of feelings may be
      preserved even when awareness of cognitive deficits is impaired.

PMID- 27712488
TI  - Responsibility and decision making help to minimise effects of AD.
AB  - People with Alzheimer's disease (AD) are affected not only by changes in the
      brain but also by the way they react to the effect of these changes and the way
      they are treated by others. When treated by 'healthy others' in a way that could
      be described as 'malignant social psychology', the person with AD can become
      depressed and angry and lose their sense of self-worth. This article discusses
      the importance of the sense of self-worth in all older people; they perform
      better on memory tests after being exposed to positive subliminal messages about
      older people.

PMID- 27712489
TI  - Working with adult abuse a training manual for people working with vulnerable
      adults Jacki Pritchard Working with adult abuse a training manual for people
      working with vulnerable adults Jessica Kingsley Publishers 2007 L50 416 978 1
      84310 509 1 1843105098 [Formula: see text].
AB  - This training manual is an update of Working with Elder Abuse from 1996. It would
      be hugely beneficial to all professionals regardless of band/grade who work with
      adults that are potentially vulnerable. It is refreshing in that it is written in
      plain every day English, and reads as if the author is talking to you directly.

PMID- 27712491
TI  - Educating vulnerable people on the benefits of influenza vaccines.
AB  - Influenza causes 3,000-6,000 deaths each year in the UK, mainly in people aged 65
      or older. Modern influenza vaccines are safe and effective with between 60 per
      cent and 90 per cent success rate. Systemic side effects are no more common than
      placebo, and local side effects are mild and short lived. Despite this, some
      older people are reluctant to take up the vaccine and the reasons for this are
      not straightforward.

PMID- 27712490
TI  - Dignity, drugs and discharge.
AB  - Speaking at 'Nursing older people on the wards', an excellent conference hosted
      by Healthcare Events at RCN HQ in London last month, Dr Nadia Chambers urged the
      audience to think about going home - not that they needed much encouragement as
      hers was the last presentation of the day.

PMID- 27712492
TI  - Falls can be an indicator of underlying medical or social problems.
AB  - Falls are the most common reason for A&E attendance in people over 55. Between 10
      20 per cent of falls cause injury of some sort and even apparently 'minor' soft
      tissue injury can lead to significant loss of function in frailer people. Falls
      can also result in distressing 'long lie' where victims are unable to get up, and
      this may lead to pressure damage, dehydration or hypothermia. Falls are also
      frequently an indicator of underlying medical or social problems and the first
      'red flag' suggesting that something is wrong.

PMID- 27712493
TI  - Heather Middleton.
AB  - The things the older people I have known value most are the company of family and
      friends, being seen as a person (or even just 'being seen'), and being able to
      maintain their independence. The challenge for nurses and carers is to see the
      person, not their age, and to find ways to enable them to keep their independence
      in whatever way they can.

PMID- 27712495
TI  - Website launch has potential to promote digital inclusion.
AB  - The Department for Work and Pensions has launched a social networking website
      akin to Facebook and Myspace to enable the over-50s to communicate with the
      government and each other about issues that concern them. The site,
      www.generationxperience.wordpress.com , is a pilot scheme.

PMID- 27712494
TI  - Falls prevention strategies.
AB  - Multifactorial assessment and targeted intervention to reduce falls among older
      people has for some time been considered an effective intervention ( Gillespie et
      al 2003 ; Chang et al 2004 ). This practice normally involves identifying the
      risk status of individuals and then intervening to reduce such risks by, for
      example, medication review, offering professionally prescribed gait training,
      exercise programmes toimprove strength and balance, modification of environmental
      hazards and so on. It has been the cornerstone of UK NHS policy implemented by
      NICE ( 2004 ).

PMID- 27712496
TI  - Sharing funding for long term care.
AB  - The issue of funding for long term care always generates considerable debate, and
      the situation is not helped by the existence of different polices across the four
      countries of the UK. In England, long term care is means tested, whereas in
      Scotland it is free. However, conclusions drawn in a new report, The Future of
      Care Funding - Time for a Change suggest that the funding system of long term
      care is not fit for purpose.

PMID- 27712497
TI  - Helping older people to maintain a healthy body weight.
AB  - Unintentional weight loss is a common problem in older people, with those in
      institutions being at greatest risk. NICE guidelines recommend opportunistic
      screening of older people when they attend for health checks or flu injections,
      and if there is cause for concern such as poor wound healing or impaired
      swallowing.

PMID- 27712500
TI  - And in other news....
AB  - Newspapers these days are stuffed with articles on health and wellbeing, many of
      them fanciful or, at worst, incorrect. Part of the problem is the desire to
      distil complex research into a headline which may bear little relationship to the
      truth.

PMID- 27712499
TI  - Historic appointment.
AB  - On 21 April, Ruth Marks will become the first Commissioner for Older People in
      Wales - one of only a handful of such positions in the world. Wales has a higher
      proportion of older people than anywhere else in the UK and Ms Marks, whose role
      is independent of the Assembly Government, is charged with ensuring that the
      interests of people who are aged 60 and over are 'safeguarded and promoted' More
      than one in five of Wales' population is aged over 60, and in 20 years' time this
      group will comprise just under a third while the number of people over 85 will
      rise by over a third.

PMID- 27712501
TI  - Now, voyager.
AB  - Diana Athill, now 90, has spent a life in books. As a writer, editor and
      publisher she has, as expected, a way with words, employed to great effect in A
      Final Farewell to Sex, published in The Guardian Weekend magazine (
      http://tinyurl.com/2gg20y ).

PMID- 27712502
TI  - Side-effects of antibiotics can vary from mild to life threatening.
AB  - In his overview of antibiotic therapy, Kevin Frost, the senior clinical
      pharmacist for antibiotics at Airedale NHS Trust, West Yorkshire, describes the
      factors that should be taken into account when choosing an antibiotic. These
      include.

PMID- 27712503
TI  - Essential geriatrics Henry Woodford Essential geriatrics Radcliffe 2007 320
      L24.95 9781846191701 184619170X [Formula: see text].
AB  - Nurses with an interest in medicine for older people will find this book
      invaluable. It is only 300 pages but contains masses of information presented in
      a way that is easily accessible for those with even a rudimentary knowledge of
      the subject. Diagrams are refreshing in their simplicity.

PMID- 27712504
TI  - The 'eye-light' of 2007.
AB  - Patients with eye disease on both side of the Atlantic received some Christmas
      cheer with the news that drugs for age-related macular degeneration (AMD) will be
      made more accessible.

PMID- 27712506
TI  - Downfall.
AB  - For anyone working in falls prevention it was a disheartening end to the year: a
      review of 19 trials, involving almost 6,500 older people in eight countries,
      found no strong evidence that falls prevention programmes work( Gates et al 2007
      ).

PMID- 27712507
TI  - Sight/stroke meeting.
AB  - The Stroke Association together with the Royal National Institute of the Blind is
      holding a one-day conference on Monday 3rd March in Devon on stroke related eye
      conditions, assessment of vision, and advances in rehabilitation. Each year an
      estimated 150,000 people in the UK have a stroke ( page 14 ). Of these, about a
      third is likely to die in the first ten days, a third is likely to make a
      recovery in one month and a third is likely to be left disabled and needing
      rehabilitation. Sight problems in stroke are associated with reduced activities
      of daily living and with falls. Because many visual problems are easily corrected
      or improve with intervention, formal screening for visual problems in stroke
      patients in a rehabilitation setting may be beneficial. Conference details are
      available on 0117 935 7750 or Rnibsouthwest@rnib.org.uk.

PMID- 27712510
TI  - Intensive Clinical Studies.

PMID- 27712514
TI  - Still Rockin.

PMID- 27712511
TI  - Anakinra in resistant gout: a case report.
AB  - Gout is a common cause of inflammatory arthritis. The classical treatment options
      in an acute gout attack are non-steroidal anti-inflammatory drugs, colchicine,
      and corticosteroids. Interleukin-1 inhibition has been shown to be an effective
      alternative when non-biologic therapies are ineffective or contraindicated.
      Herein, we report the case of a 69-year-old female who presented with
      polyarticular tophaceous gout treated successfully with anakinra.

PMID- 27712518
TI  - At-risk groups 'may miss out' on flu vaccinations.
AB  - The government's annual flu vaccination campaign is underway again, with an
      uptake target of 70 per cent among those aged 65 and over.

PMID- 27712516
TI  - Under the microscope.
AB  - Under the Health and Social Care Act 2001, local authorities have been given new
      powers to scrutinise the work of the NHS in the local area (including decisions
      on NHS reorganisations and service change).

PMID- 27712519
TI  - Demands grow for better stroke care.
AB  - Pressure is mounting on the government to improve the care of people who have
      suffered a stroke.

PMID- 27712520
TI  - Joint conference.
AB  - The RCN Forum for Nurses Working with Older People and the RCN Mental Health and
      Older People Forum have come together this year in the spirit of partnership and
      participation to arrange one-day conferences on consecutive days so that members
      have the opportunity to stay over and enjoy both.

PMID- 27712521
TI  - Developing links mental health and older people.
AB  - Life seems full of conflicting choices. Take football teams: do you support the
      local team with no chance of big success but which is friendly, sporting and
      inviting, or do you go for the big side with big names, big money and a good
      chance of winning something silver? These difficulties can really exercise the
      mind. This pattern seems to sum up many of the decisions that one has to take: do
      you go big or do you stay small?

PMID- 27712522
TI  - The Pool Activity Level (PAL) Instrument for Occupational Profiling Jackie Pool
      The Pool Activity Level (PAL) Instrument for Occupational Profiling Second
      edition Jessica Kingsley Publishers 96pp L22.50 1843100800 1843100800.
AB  - This easy-to-access introduction and workbook to cover the use of the Pool
      Activity Instrument is a useful addition to the growing resources available under
      the umbrella of the Bradford Dementia Group. In this second edition, it has been
      modified to account for suggestions from the field and this shows from its clear
      and practice-based approach.

PMID- 27712523
TI  - Working with Dysphagia Working with Dysphagia Lizzy Marks and Deirdre Rainbow
      Speechmark 152pp A4 wirebound, L35 + VAT 0863882498 0863882498.
AB  - This book explores all aspects of swallowing difficulty including relevant
      anatomy and physiology and detailed discussion of assessment techniques such as
      videofluoroscopy and electromyography. The authors highlight the impact that
      dysphagia can have on all aspects of a person's life with fear of choking leading
      to malnutrition and social withdrawal.

PMID- 27712524
TI  - Nurse Prescribing Nurse Prescribing Jennifer L Humphries and Joyce Green Palgrave
      137pp , L16.99 0 333 726112 0333726112.
AB  - This is a small book on a big development. It is for all healthcare professionals
      with an interest in community health care and primary health care, and offers a
      broad scope of related topics rather than great detail. There is an impressive
      range of contributors, from the nurse academic to the pharmacist, although the
      views of a GP would have added an interesting dimension.

PMID- 27712525
TI  - A bitter pill to swallow.
AB  - If you are old and have your meals prepared for you, beware of the powdery
      flavour you think you sense in the sandwich filler, the suspicious extra crunch
      in your breakfast cereal, or the strange alien taste in Sunday lunch. Patients in
      health and care settings would do well in future to emulate those powerful but
      paranoid rulers who required a personal taster to take a bite of each course
      before they ate it. They might otherwise find themselves consuming medicines
      which they would have chosen to decline; covert medication, alas, is back on the
      menu.

PMID- 27712527
TI  - Trusts stumble over NSF falls target.
AB  - Targets set in the National Service Framework for Older People (NSF) to reduce
      injuries caused by falls may not be met, according to new research.

PMID- 27712526
TI  - Draft bill response.
AB  - Many readers will be aware that in June of this year the government published a
      draft Mental Health Bill to introduce a new framework for mental health care in
      England and Wales. This is arguably the biggest review of the mental health
      system since the 1950s. Many people regard this overhaul as both necessary and
      long overdue. However, concerned organisations, including the RCN, believe that
      there are areas of serious concern within the draft Bill, which have important
      implications for users of mental health services.

PMID- 27712528
TI  - Veterans' battles still to be won.
AB  - Now 102 to 107 years of age, Britain's most senior war veterans will soon be
      gathering to celebrate their latest achievement. On November 5 the members of the
      World War One Veterans Association will meet at the the World War One Veterans
      Association will meet at the Imperial War Museum in London to launch their new
      book, The Forgotten Voices of the Great War: A New History of World War One, a
      compilation of their memories and reflections.

PMID- 27712529
TI  - Events.
AB  - November 6 - 7 Shared investment conference and exhibition RCN Continence Care
      Venue: The International Centre, Telford Fee: L155 - L235 Contact: Kathryn Clark
      Tel: 020 7647 3585 Fax: 020 7647 3411 Email: continence@rcn.org.uk.

PMID- 27712532
TI  - The Sacred and Profane: An Editorial.

PMID- 27712534
TI  - Disguised Countertransference in Institutions.

PMID- 27712533
TI  - Letters.

PMID- 27712535
TI  - The Double Life of a Psychiatrist.

PMID- 27712536
TI  - Identity and Individuality in the Nouveau-Religious Patient.

PMID- 27712537
TI  - Comparing Males' and Females' Perspectives through Family.Self-Report.

PMID- 27712538
TI  - ReligIon and Secularization in Psychiatric Practice: Three Examples.

PMID- 27712539
TI  - Communication Deviance in Adolescence and Adulthood.

PMID- 27712540
TI  - Psychoeducational Family Therapy for Schizophrenia.

PMID- 27712544
TI  - Internet-delivered transdiagnostic and tailored cognitive behavioral therapy for
      anxiety and depression: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - Anxiety and depressive disorders are often comorbid. Transdiagnostic and tailored
      treatments seem to be promising approaches in dealing with comorbidity. Although
      several primary studies have examined the effects of Internet-delivered cognitive
      behavior therapy (iCBT) for anxiety and depression, no meta-analysis including
      different types of iCBT that address comorbidity has been conducted so far. We
      conducted systematic searches in databases up to 1 July 2016. Only randomized
      trials comparing transdiagnostic/tailored iCBT for adult anxiety and/or
      depression with control groups were included. Nineteen randomized trials with a
      total of 2952 participants that met inclusion criteria were analyzed. The quality
      of the studies was high, however the blinding criteria were not fulfilled. The
      uncontrolled effect size (Hedges' g) of transdiagnostic/tailored iCBT on anxiety
      and depression outcomes was large and medium for quality of life. The controlled
      effect size for iCBT on anxiety and depression outcomes was medium to large
      (anxiety: g = .82, 95% CI: .58-1.05, depression: g = .79, 95% CI: .59-1.00) and
      medium on quality of life (g = .56, 95% CI: .37-.73). Heterogeneity was small
      (quality of life) to moderate (anxiety, depression). There was a large effect on
      generic outcome measures and a moderate effect on comorbidities. When compared to
      disorder-specific treatments there were no differences on anxiety and quality of
      life outcomes, however there were differences in depression outcomes.
      Transdiagnostic and tailored iCBT are effective interventions for anxiety
      disorders and depression. Future studies should investigate mechanisms of change
      and develop outcome measures for these interventions.

PMID- 27712545
TI  - How does the small picture relate to the bigger picture?

PMID- 27712546
TI  - The refugee crisis: We cannot ignore this for much longer.

PMID- 27712547
TI  - (What) do you believe?: Therapist spiritual/religious/non-religious self
      disclosure.
AB  - OBJECTIVE: Spiritual/religious/non-religious (S/R/N) identity development is
      often neglected in psychotherapy training and represents an area where
      psychotherapists feel they lack competence. Such feelings can become even more
      pronounced when it comes to S/R/N self-disclosure. This study explores the
      decisions therapists make regarding self-disclosure, which impacts the
      psychotherapy process. METHOD: This grounded theory study explores
      psychotherapists' S/R/N self-disclosure based on qualitative interviews with 21
      psychotherapists representing varied theoretical orientations and spiritual,
      religious, atheist, and agnostic backgrounds. RESULTS: Findings reveal that while
      some self-disclosure happens on an explicit level, more often psychotherapists
      find implicit ways to share S/R/N aspects of the self for purposes of enhancing
      the therapeutic alliance and to convey openness. Psychotherapists also attempt to
      avoid the topic altogether, either to protect the therapeutic relationship or
      because of unresolved S/R/N identity in the therapist. CONCLUSIONS: Developing
      skills related to S/R/N self-disclosure represents an important aspect of
      multicultural competence, which can impact clients' feelings of safety and
      comfort discussing their own S/R/N identity. This capacity is strongly influenced
      by the therapist's self-awareness regarding S/R/N identity. Suggestions for
      engaging S/R/N identity and disclosure in supervisory experiences and academic
      preparation are discussed.

PMID- 27712550
TI  - Delinquency, Drug Abuse and Alcoholism.

PMID- 27712548
TI  - An Integrative Control Theory of Delinquent Behavior: A Validation 1976-1985.

PMID- 27712551
TI  - Are There Any Successful Men from Criminogenic Backgrounds?

PMID- 27712552
TI  - The residential context of health in Australia: No longer the lucky country?
AB  - This paper introduces the special issue focused on the relationship between
      residence and health in Australia. We present six papers conducted in different
      Australian states that demonstrate different elements of the complex impact of
      residential context on health. Through this series of papers, we demonstrate the
      impact of housing quality and safety on vulnerable populations, but also the way
      in which processes around housing (e.g., data collection, renewal, allocation)
      can have either negative or positive outcomes. The broader residential context
      (i.e., neighborhood, community, geographic location) also must be considered in
      housing decisions, along with variables that closely track housing (e.g., stigma,
      poverty). Australia is in the middle of a housing crisis that can still be
      resolved in positive ways if adequate attention is given to the nuances and
      complexities of housing decisions.

PMID- 27712553
TI  - A place to call my own: Young people with complex disabilities living in long
      term care.
AB  - It is important to consider the nature of home in more detail when thinking about
      living environments for vulnerable groups of people, especially as it has been
      found that the nature of home can impact on the quality of life. The aim of this
      study was to understand the "lived experience" of home for a group of young
      people with complex disabilities who had recently relocated to a specially
      designed residential apartment building. Multiple domains of home, as they were
      experienced over time, were examined through a series of semi-structured
      interviews conducted with seven residents at their apartments. The findings
      revealed two major themes ("perceived quality of the place" and "identity in
      place") that were inextricably interlinked. To the extent that they overlapped,
      the experience of home was enhanced. The interaction between the two themes was
      associated with a dynamic ongoing process whereby the sense of home was either
      created or damaged ("deconstruction and reconstruction of home"). The current
      study has implications for how residential care workers are trained and supported
      if the well-being of individuals with complex disabilities is to be promoted
      within residential settings.

PMID- 27712554
TI  - Where you live and who you live with matters: Housing and mental health.
AB  - This article considers the relationship between where a person lives and who they
      live with and their mental health and well-being. In particular, this article
      considers the regional locale as an important factor in understanding the
      perspective of a person with lived experience of mental illness. This article
      questions the influential, yet somewhat narrow, argument that living in the
      community and in the family home is somehow better for people with mental
      illness. The arguments presented in this article illustrate that for some people
      with mental illness, the issues of stigma, autonomy, and lack of alternatives
      (choice) are just as prevalent for them now, living in the community, as when
      they lived in institutions. The assumption that place alone can redress the lack
      of choice and autonomy is unfounded.

PMID- 27712555
TI  - The cunning of data in Indigenous housing and health.
AB  - This article explores why it is so difficult to provide and sustain decent public
      housing in Indigenous communities, highlighting the curious role that data
      reporting and analysis plays in perpetuating this state of affairs. Drawing on
      data amassed by the Housing for Health (HFH) program that has focused on "health
      hardware" functionality in almost 9,000 houses in over 215 communities across
      Australia, we note inroads made to the language of policy (through, for example,
      the development of a National Indigenous Housing Guide). However, we also note
      the more limited effect on those policy practices that ordain substandard housing
      function. There is an intimate relationship between this outcome and the
      paradoxical state of the Indigenous housing and health evidence base, a field
      which is simultaneously awash with multiple databases providing synoptic
      information at regional, state/territory, and national levels, yet lacking
      specificity in relation to the health-enabling status of housing infrastructure.

PMID- 27712556
TI  - Public housing renewal and social determinants of health.
AB  - This article draws on the concept of residential context of housing and its
      relationship to health. It considers a bundle of changes through implementation
      of a housing renewal initiative as part of the Carlton Housing Estate Upgrading
      Project in Melbourne, Australia. Beyond the quality and appropriateness of the
      housing, pertinent factors explored include social networks, safety and security,
      and green open space. Data collection for the research project included in-depth
      interviews with public housing tenants, private residents, and service providers
      who live on and service the estate, as well as neighborhood observations and
      participation in on-site events. A key finding was that the relational processes
      of how tenants were related to by others-specifically, the way housing was
      reallocated during the processes of renewal-affected social housing tenants' self
      perceived health and well-being.

PMID- 27712557
TI  - Poor housing quality: Prevalence and health effects.
AB  - Housing is a central component of productive, healthy, and meaningful lives, and
      a principle social determinant of health and well-being. Surprisingly, though,
      evidence on the ways that housing influences health in Australia is poorly
      developed. This stems largely from the fact that the majority of the population
      are accommodated in good quality housing. The dominance of a "good housing
      paradigm" means that households living in poor quality and unhealthy housing are
      doubly disadvantaged-by the quality of their housing and because policy makers in
      Australia do not acknowledge the health effects of housing. In this article, we
      examine the relationship between health outcomes and quality of housing. We base
      our analysis on data from the Household Income and Labour Dynamics in Australia
      (HILDA) survey, a panel dataset that is representative across Australia. We find
      a sizeable, policy-important, and to date under-acknowledged cohort of
      Australians whose health is influenced by poor-condition dwellings.

PMID- 27712558
TI  - Self-assessed health status and neighborhood context.
AB  - In recent years, there has been growing interest in the relationship between the
      characteristics of neighborhoods and the health and well-being of residents. The
      focus on neighborhood as a health determinant is based on the hypothesis that
      residing in a disadvantaged neighborhood can negatively influence health outcomes
      beyond the effect of individual characteristics. In this article, we examine
      three possible ways of measuring neighborhood socio-economic status, and how they
      each impact on self-reported health status beyond the effect contributed by
      individual-level factors. Using individual-level data from the Household Income
      and Labor Dynamics Australia survey combined with neighborhood-level (suburb)
      data, we tested the proposition that how one measures neighborhood socio-economic
      characteristics may provide an important new insight into understanding the links
      between individual-level outcomes and neighborhood-level characteristics. The
      findings from the analysis illustrate that although individual-level factors may
      be important to understanding health outcomes, how one accounts for neighborhood
      level socio-economic status may be equally important. The findings suggest that
      in developing place-based health programs, policy makers need to account for the
      complex interactions between individual drivers and the potential complexities of
      accounting for neighborhood socio-economic status.

PMID- 27712564
TI  - Protective effect of wild Corni fructus methanolic extract against acute
      alcoholic liver injury in mice.
AB  - BACKGROUND: In Chinese folk medicine, Corni fructus (C. fructus) has
      traditionally been used to improve liver function, although the mechanism
      underlying its activity remains unclear. The aim of the present study was to
      evaluate the protective effects of wild C. fructus methanolic extract against
      acute alcoholic liver injury. METHODS: Alcohol was administered to mice for three
      consecutive days, either alone or in combination with C. fructus methanolic
      extract (50, 100, or 200 mg/kg body weight/d). Serum and liver tissue were
      collected from the animals and subjected to biochemical and histopathological
      analyses. RESULTS: C. fructus significantly alleviated alcohol-induced liver
      injury by reducing serum alanine aminotransferase, aspartate aminotransferase,
      and thiobarbituric acid reactive species, inhibiting hydroxyl radicals (*OH), and
      increasing total superoxide dismutase, glutathione peroxidase, and glutathione in
      the liver (P < 0.05). In addition, the C. fructus treatment inhibited the
      expression and activity of cytochrome P450 2E1 (P < 0.05). CONCLUSIONS: C.
      fructus could be a promising natural substance for ameliorating acute alcohol
      induced oxidative stress and hepatic injury.

PMID- 27712565
TI  - Confronting the opioid epidemic through publication, promotion, and dissemination
      of evidence-based addiction scholarship.

PMID- 27712566
TI  - Corrigendum.

PMID- 27712567
TI  - Development and Optimization of Controlled Porosity Osmotic Tablets of
      Lamotrigine Solid Dispersion.
AB  - BACKGROUND: The purpose of this study was to investigate the application of a
      controlled porosity osmotic tablet (CPOT) utilizing solid dispersion (SD) of
      poorly soluble drug. The patents on Cyclobenzaprine HCl (US4968507 A) and
      Venlafaxine salts (EP 2085078 A1) helped in the selection of drug and polymers.
      METHOD: The SDs having different ratio of drug to carrier (PVP K 30) were
      prepared by kneading method and optimized. Effect of three independent variables,
      total amount of osmogen (mannitol& potassium chloride), total amount of polymer
      (polyethylene oxide WSR 301, hydroxy propyl methyl cellulose K100 M) and
      polymer1: polymer 2 ratio were investigated using Box Behnken design. Core and
      coated tablets were evaluated for various parameters. In-vitro drug release
      profiles of CPOT tablets were compared with reference product Diffcore tablet,
      Lamictal XR (GlaxoSmith Kline Inc., USA). RESULTS: All formulations showed
      acceptable parameters. Drug release from CPOT was determined as complete, zero
      order and pH-independent within the physiological pH range of the GI tract. Drug
      release was directly proportional to initial level of polymers and osmogens.
      CONCLUSION: The present results confirmed that prepared LTG SD serves as
      solubility modulator. Further, CPOT of LTG based on SD proved to be successful in
      delivering the drug in a controlled manner ensuring the once daily dosing for the
      treatment of convulsive disorders.

PMID- 27712568
TI  - Formulation Development and Optimization of Matrix Tablet of Tramadol
      Hydrochloride.
AB  - BACKGROUND: The aim of the present investigation is to formulate and optimize
      oral sustained release matrix tablet of highly water soluble drug Tramadol HCl
      and to evaluate the effect of varying concentration of hydrophilic and
      hydrophobic polymer on drug release, based on a survey done on the recent patents
      of Tramadol HCl (US7374781, CA 2479252) and sustained release matrix tablets.
      METHODS: The tablets were prepared by double granulation process, by melt
      granulation and wet granulation technique using Carnauba wax (CW) and HPMC K100
      as release retardant. RESULTS: Pre and post compression factors were evaluated
      and all the parameters were found within the limit. The drug release data were
      subjected to different models in order to evaluate release kinetics and mechanism
      of drug release. The prepared formulations showed drug release in the range 100+/
      2% in 6hrs, 7hrs, 8hrs and 9hrs and upto 12 hrs respectively. The optimized
      tablet having 25% CW and 20% HPMC showed sustained drug release pattern.
      Hydrophilic matrix of HPMC alone could not control the Tramadol release
      effectively for 12 h whereas when combined with CW could slow down the release of
      drug and can be successfully employed for formulating sustained-release matrix
      tablets. Similarity factor, f2 shows the test and reference profile are
      identical. CONCLUSION: Double granulation technique with CW and HPMC K100 proved
      as a better technique for sustaining the drug release from the matrix tablet.

PMID- 27712570
TI  - Editorial (Thematic Issue: Nanoparticles for Brain and Tumor Targeting Delivery).

PMID- 27712569
TI  - Liposomal Drug Delivery System for Cancer Therapy: Advancement and Patents.
AB  - BACKGROUND: In this review article, authors reviewed about the liposomes which
      are amongst various drug delivering systems for the delivery of the therapeutic
      agents at the target site. METHODS: Advances in liposomal drug delivery systems
      for the cancer therapy have enhanced the therapeutic levels of the anticancer
      moieties. Liposomes show promising action on the tumor by incorporating less
      amount of drug at the target site, with minimum toxic effect and maximum
      therapeutic effect and thereby enhancing the bioavailability. RESULTS: Liposome
      based drug delivery systems provide the potential to elevate the effect of drug
      concentration in tumor cells. Manuscript briefly describes the role of liposomes
      in cancer therapy and various patents based on the same.

PMID- 27712571
TI  - Editorial (Thematic Issue: New Developments in Medicinal Chemistry Highlighting
      Diverse Heterocyclic Ring Systems : Part I- Five Membered Ring Systems).

PMID- 27712572
TI  - Old, New and Hidden Causes of Perioperative Hypersensitivity.
AB  - Perioperative hypersensitivity reactions are rare, often life-threatening events,
      and subsequent investigations to identify the culprit are important to avoid re
      exposure. All exposures in the perioperative setting may potentially be the cause
      of a hypersensitivity reaction, but drugs administered intravenously such as
      neuromuscular blocking agents (NMBA), induction agents and antibiotics have
      traditionally been reported to be implicated most commonly. It has recently
      become apparent that there are geographical differences in sensitization patterns
      related to variation in exposures, referral patterns and performance and
      interpretation of investigations. Differences in sensitization to NMBAs are
      partly explained by cross sensitization to pholcodine, an ingredient in cough
      medicines available in some countries. While NMBAs are the most common causes of
      perioperative hypersensitivity in some countries, this may not necessarily be the
      case in all countries. New and hidden allergens have emerged as causes of
      perioperative hypersensitivity such as blue dyes, chlorhexidine and excipients.
      Detailed knowledge of the events at the time of reaction is necessary to identify
      potential culprits including rare and hidden allergens. Cooperation between
      allergists and anaesthetists, or other staff present perioperatively, is often
      needed to identify hidden or even undocumented exposures. The objectives of this
      review are to provide an overview of the history of investigation of
      perioperative hypersensitivity, to describe the differences in causes of
      perioperative hypersensitivity emerging over time and to increase awareness about
      the "hidden allergens" in the perioperative setting. Some practical advice on how
      to approach the patient testing negative on all initial investigations is also
      included.

PMID- 27712573
TI  - Diagnosing beta-Lactam Hypersensitivity.
AB  - Hypersensitivity reactions to beta-lactam antibiotics are commonly reported. They
      can be classified as immediate or non-immediate according to the time interval
      between the last drug administration and their onset. Immediate reactions occur
      within one hour after the last drug administration and are manifested clinically
      by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock;
      they may be mediated by specific IgEantibodies. Non-immediate reactions occur
      more than one hour after the last drug administration. The most common
      manifestations are maculopapular exanthemas; specific T lymphocytes may be
      involved in this type of manifestation. In the diagnostic evaluation of
      hypersensitivity reactions to beta -lactam antibiotics, the patient's history is
      fundamental. The allergy examination is based on in vitro and in vivo tests
      selected on the basis of the clinical features and the type of reaction,
      immediate or non-immediate. Immediate reactions can be assessed in vitro by serum
      specific IgE assays and basophil activation tests and in vivo by immediate
      reading skin tests and, in selected cases, drug provocation tests (DPTs). Non
      immediate reactions can be evaluated mainly by delayed-reading skin tests, patch
      tests, and DPTs.

PMID- 27712574
TI  - Progress in Polysaccharide Derivatization and Properties.
AB  - Polysaccharides and their derivatives have opened up new industrial field because
      of their special biochemical functions. Their biological immune, biological
      inhibition, antioxidant and anticoagulant properties have begun to help people
      enhance their physique, the fight against aging. Molecular modification is an
      important way to study the structure-activity relationship of polysaccharides
      which should be focused on. After molecular modification, various derivatives of
      different types of structures and biological activities are gained. Chemical
      modification of polysaccharides, e.g., carboxymethylation, sulfonylation,
      phosphorylation, acetylation, and hydroxypropylation, cationic or other
      derivatives, can improve their bioavailability and applications in different
      biological systems.

PMID- 27712575
TI  - Selective Serotonin Reuptake Inhibitors and Serotonin and Noradrenaline Reuptake
      Inhibitors Improve Cognitive Function in Partial Responders Depressed Patients:
      Results from a Prospective Observational Cohort Study.
AB  - BACKGROUND: Major Depressive disorder (MDD) is often accompanied by cognitive
      deficits, involving attention, learning, memory and executive functioning.
      Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin and Noradrenaline
      Reuptake Inhibitors (SNRIs) show efficacy on affective symptoms, but it is
      unclear whether or not they improve cognitive symptoms. METHODS: We carried out a
      12 week-prospective observational study in two cohorts of recurrent moderate
      severe partial responder MDD patients, to test the hypothesis that SSRIs and/or
      SNRIs may affect cognitive symptoms and assess whether or not such an effect was
      correlated to their effect on affective symptoms. All patients underwent
      cognitive and neuropsychiatric assessment at baseline, 4- and 12-week follow-up.
      Thirty-three patients in the SSRI- and sixteen patients in the SNRI-cohort
      completed the follow-up. RESULTS: Both SSRIs and SNRIs reduced affective symptoms
      and improved global cognitive function. Both SSRIs and SNRIs improved executive
      function and verbal memory. Global cognitive function, verbal memory and
      executive function improved both in full and partial responder patients. Finally,
      there was no correlation between baseline Mini Mental State Examination, Montreal
      Cognitive Assessment and Frontal Assessment Battery scores and the mean change in
      Hamilton Psychiatric Rating scale for Depression or Beck Depression Inventory at
      the end of the 12 weeks of treatment. CONCLUSION: Present data show that SSRIs
      and SNRIs improve cognitive symptoms in MDD independently from their efficacy on
      affective symptoms. Affective and cognitive symptoms may represent distinct
      psychopathological dimensions of MDD with different response to antidepressant
      drugs.

PMID- 27712576
TI  - Multiple Targets for the Management of Alzheimer's Disease.
AB  - AD is a progressive and irreversible neurodegenerative disease and the most
      common cause of dementia in the elderly population. Betaeta- amyloid cascade
      formation along with several cytoskeleton abnormalities succeeding to the
      hyperphosphorylation of microtubule-associated tau protein in neurons leads to
      the elicitation of several neurotoxic incidents. As an outcome of these
      phenomena, steady growth of dementia in aged population is becoming ubiquitous in
      both developed and developing countries. Thus, the key aspiration is to endow
      with stable daily life functionality to the person suffering from dementia and to
      cut down or slower the symptoms of disease leading to disruptive behavior. In
      sight of this, the proteins amyloid-beta, BACE-1, RAGE and AChE are being aimed
      for the treatment of AD successfully. Currently, there are several medicines for
      the treatment of AD under survey like Galangin, Cymserine, Tolserine,
      Bisnorcymserine and Huperzine A. The article emphasizes clinical and
      neurobiological aspects of AD. The purpose of this review article is to provide a
      brief introduction of AD along with the related concept of beta-secretase, beta
      amyloid and neurotransmitter in the progression of disease. In the present
      review, we summarize the available evidence on the new therapeutic approaches
      that target amyloid and neurotransmitter in the AD.

PMID- 27712577
TI  - Editorial (Thematic Issue: Medicinal Inorganic Chemistry: Identification of New
      Targets in Drug Discovery).

PMID- 27712578
TI  - SINGLE CELLS: SHUT YOUR EYES AND SEE.
AB  - Increasingly, researchers are turning to single cells to explore basic biology.
      Jeffrey Perkel looks at the technology making single-cell experiments a reality.

PMID- 27712579
TI  - TO EDIT OR NOT: THE NGAGO STORY.
AB  - New genome-editing approaches always receive widespread attention. But in the
      case of a novel Argonaute-based technique published last spring, attention has
      been particularly intense.

PMID- 27712580
TI  - PCR amplification of GC-rich DNA regions using the nucleotide analog N4-methyl-2'
      deoxycytidine 5'-triphosphate.
AB  - GC-rich DNA regions were PCR-amplified with Taq DNA polymerase using either the
      canonical set of deoxynucleoside triphosphates or mixtures in which the dCTP had
      been partially or completely replaced by its N4-methylated analog, N4-methyl-2'
      deoxycytidine 5'-triphosphate (N4me-dCTP). In the case of a particularly GC-rich
      region (78.9% GC), the PCR mixtures containing N4me-dCTP produced the expected
      amplicon in high yield, while mixtures containing the canonical set of
      nucleotides produced numerous alternative amplicons. For another GC-rich DNA
      region (80.6% GC), the target amplicon was only generated by re-amplifying a gel
      purified sample of the original amplicon with N4me-dCTP-containing PCR mixtures.
      In a direct PCR comparison on a highly GC-rich template, mixtures containing N4me
      dCTP clearly performed better than did solutions containing the canonical set of
      nucleotides mixed with various organic additives (DMSO, betaine, or ethylene
      glycol) that have been reported to resolve or alleviate problems caused by
      secondary structures in the DNA. This nucleotide analog was also tested in PCR
      amplification of DNA regions with intermediate GC content, producing the expected
      amplicon in each case with a melting temperature (Tm) clearly below the Tm of the
      same amplicon synthesized exclusively with the canonical bases.

PMID- 27712581
TI  - Optimization of Diamond Nucleic Acid Dye for quantitative PCR.
AB  - Here, we evaluate Diamond Nucleic Acid Dye (DD) for use in quantitative PCR
      (qPCR) applications. Although DD is a commercially available stain for detection
      of DNA separated by gel electrophoresis, its use as a detection dye in qPCR has
      yet to be described. To determine if DD can be used in qPCR, we investigated its
      inhibitory effects on qPCR at concentrations ranging 0.1-2.5*. Serial dilution of
      DNA was used to determine the efficiency, sensitivity, and linearity of DD
      generated qPCR data in comparison to other commonly used fluorescent dyes such as
      SYBR Green (SG), EvaGreen (EG), and BRYT Green (BG). DD was found to be
      comparable with other dyes for qPCR applications, with an R2 value >0.9 and an
      efficiency of 0.83. Mitochondrial DNA (mtDNA) target signals were successfully
      produced by DD over a DNA dilution range of ~28 ng- 0.28 pg, demonstrating
      comparable sensitivity to the other dyes investigated. Cq values obtained using
      DD were lower than those using EG by almost 7 cycles. We conclude that Diamond
      Nucleic Acid Dye is a cheaper, less toxic alternative for qPCR applications.

PMID- 27712582
TI  - Spotsizer: High-throughput quantitative analysis of microbial growth.
AB  - Microbial colony growth can serve as a useful readout in assays for studying
      complex genetic interactions or the effects of chemical compounds. Although
      computational tools for acquiring quantitative measurements of microbial colonies
      have been developed, their utility can be compromised by inflexible input image
      requirements, non-trivial installation procedures, or complicated operation.
      Here, we present the Spotsizer software tool for automated colony size
      measurements in images of robotically arrayed microbial colonies. Spotsizer
      features a convenient graphical user interface (GUI), has both single-image and
      batch-processing capabilities, and works with multiple input image formats and
      different colony grid types. We demonstrate how Spotsizer can be used for high
      throughput quantitative analysis of fission yeast growth. The user-friendly
      Spotsizer tool provides rapid, accurate, and robust quantitative analyses of
      microbial growth in a high-throughput format. Spotsizer is freely available at
      https://data.csiro.au/dap/landingpage?pid=csiro:15330 under a proprietary CSIRO
      license.

PMID- 27712583
TI  - Extraction of high-molecular-weight genomic DNA for long-read sequencing of
      single molecules.
AB  - De novo sequencing of complex genomes is one of the main challenges for
      researchers seeking high-quality reference sequences. Many de novo assemblies are
      based on short reads, producing fragmented genome sequences. Third-generation
      sequencing, with read lengths >10 kb, will improve the assembly of complex
      genomes, but these techniques require high-molecular-weight genomic DNA (gDNA),
      and gDNA extraction protocols used for obtaining smaller fragments for short-read
      sequencing are not suitable for this purpose. Methods of preparing gDNA for
      bacterial artificial chromosome (BAC) libraries could be adapted, but these
      approaches are time-consuming, and commercial kits for these methods are
      expensive. Here, we present a protocol for rapid, inexpensive extraction of high
      molecular-weight gDNA from bacteria, plants, and animals. Our technique was
      validated using sunflower leaf samples, producing a mean read length of 12.6 kb
      and a maximum read length of 80 kb.

PMID- 27712584
TI  - A cost-effective method to immobilize hydrated soft-tissue samples for atomic
      force microscopy.
AB  - Immobilizing hydrated soft tissue specimens for atomic force microscopy (AFM) is
      a challenge. Here, we describe a simple and very cost-effective immobilization
      method, based on the use of transglutaminase in an aqueous environment, and
      successfully apply it to AFM characterization of human native Wharton's Jelly
      (nWJ), the gelatinous connective tissue matrix of the umbilical cord. A side-by
      side comparison with a widely used polyphenolic protein-based tissue adhesive
      (Corning Cell-Tak), which is known to bind strongly to virtually all inorganic
      and organic surfaces in aqueous environments, shows that both adhesives
      successfully immobilize nWJ in its physological hydrated state. The cost of
      transglutaminase, however, is over 3000-fold lower than that of Cell-Tak, making
      it a very attractive method for immobilizing soft tissues for AFM
      characterization.

PMID- 27712585
TI  - Knockdown of Rap1b Enhances Apoptosis and Autophagy in Gastric Cancer Cells via
      the PI3K/Akt/mTOR Pathway.
AB  - Gastric cancer (GC) is the fourth most common malignancy and the second leading
      cause of cancer mortality around the world. However, the regulatory mechanisms of
      GC tumorigenesis and cancer cell motility are completely unknown. We investigated
      the role of a RAS-related protein (Rap1b) in the progression of GC. Our results
      showed that the expression of Rap1b is aberrantly upregulated in GC tissue
      samples and human GC cell lines, and the high expression of Rap1b indicated a
      positive correlation with poor prognosis in patients with GC. Inhibition of
      endogenous Rap1b dramatically reduced the cell cycle progression but strongly
      enhanced the apoptosis capacity of human GC cell lines MKN-28 and SGC-7901 cells
      compared with the control group. Western blotting assay showed that Rap1b
      inhibition resulted in a significant increase in the ratio of LC3-II to LC3-I,
      and the levels of p62 protein were decreased in both MKN-28 and SGC-7901 cells.
      Furthermore, PI3K/Akt/mTOR activation was found to be maintained in a low level
      in the normal gastric mucosal epithelial cells, while it was significantly
      upregulated in GC cells, which could be decreased by Rap1b inhibition. The PI3K
      inhibitor LY294002 was enhanced but activator insulin-like growth factor 1 (IGF
      1) blocked the Rap1b silencing-induced enhancement of apoptosis and autophagy in
      MKN-28 and SGC-7901 cells. In conclusion, we demonstrate that Rap1b expression is
      aberrantly increased in GC, resulting in the inhibition of autophagy and
      apoptosis of GC cells by the PI3K/Akt/mTOR pathway. This might provide a new
      understanding and represent a novel therapeutic target for human GC.

PMID- 27712586
TI  - Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and
      ERK1/2 in Non-Small Cell Lung Cancer Cells.
AB  - Recently, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)
      have revolutionized non-small cell lung cancer (NSCLC) treatment. However,
      resistance remains a major obstacle. Anexelekto (AXL) is a member of receptor
      tyrosine kinases (RTKs) and shares the same downstream signaling pathways with
      EGFR, such as PI3K/AKT and MAPK/ERK. AXL overexpression in resistant tumors has
      been implicated in many previous studies in vitro and in vivo. In this study, we
      further examined whether expression of AXL and its downstream targets increased
      in gefitinib-resistant PC9 cells (PC9GR). In addition, we hypothesize that
      knocking down AXL in PC9GR and overexpressing AXL in PC9 using genetic tools can
      restore and decrease the sensitivity to gefitinib, respectively. We found that
      silencing AXL could sensitize the resistance to gefitinib, and the downstream
      pathways were significantly inhibited. Interestingly, we also discovered that
      increased AXL expression did promote the resistance, and its downstream targets
      were activated accordingly. Then 69 NSCLC patients who harbored EGFR mutation
      were recruited to analyze the expression of AXL and the association between AXL
      expression and clinical characteristics. We found that 5 of the 69 patients were
      AXL positive (about 7%), and AXL was related to tumor differentiation and tumor
      size. In this study, we concluded that the molecular mechanisms of AXL mediated
      resistance involved in the increased activity of the PI3K/AKT and MAPK/ERK1/2
      pathways, and AXL overexpression could promote resistance, but it can be weakened
      when AXL expression is silenced.

PMID- 27712587
TI  - TIPE2 Overexpression Suppresses the Proliferation, Migration, and Invasion in
      Prostate Cancer Cells by Inhibiting PI3K/Akt Signaling Pathway.
AB  - Tumor necrosis factor-alpha (TNF-alpha)-induced protein 8-like 2 (TNFAIP8L2,
      TIPE2) is involved in the invasion and metastasis of human tumors. However, the
      functional role of TIPE2 in prostate cancer remains unclear. In the present
      study, we explored the role of TIPE2 in prostate cancer and cancer progression
      including the molecular mechanism that drives TIPE2-mediated oncogenesis. Our
      results showed that TIPE2 was lowly expressed in human prostate cancer tissues
      and cell lines. In addition, restored TIPE2 obviously inhibits proliferation in
      prostate cancer cells. TIPE2 overexpression also suppresses the epithelial
      mesenchymal transition (EMT) process and migration/invasion in prostate cancer
      cells. Mechanistically, TIPE2 overexpression obviously inhibits the
      phosphorylation levels of phosphatidylinositol 3-kinase (PI3K) and Akt in
      prostate cancer cells. In conclusion, for the first time we demonstrated that
      TIPE2 overexpression may suppress proliferation, migration, and invasion in
      prostate cancer cells by inhibiting the PI3K/Akt signaling pathway. Therefore,
      TIPE2 might serve as a potential therapeutic target for human prostate cancer.

PMID- 27712588
TI  - Knockdown of REV7 Inhibits Breast Cancer Cell Migration and Invasion.
AB  - REV7 (also known as MAD2L2) is a multifunctional protein involved in DNA damage
      tolerance, cell cycle regulation, gene expression, and carcinogenesis. Although
      its expression is reportedly associated with poor prognosis in several kinds of
      human cancers, the significance of REV7 expression in breast malignancies is
      unclear. In this study, REV7 was found to be increased in breast cancer. We found
      that knockdown of REV7 inhibited the migration, invasion, and epithelial
      mesenchymal transition (EMT) of breast cancer cells. Meanwhile, overexpression of
      REV7 promoted the migration, invasion, and EMT of breast cancer cells. As shown
      by Western blot, knockdown of REV7 can promote TGF-beta1 expression. Western blot
      analysis indicated that TGF-beta1 may play a role as a downstream factor of REV7.
      Moreover, interference of TGF-beta1 can also inhibit the cell's ability for
      migration, invasion, and EMT, as well as in a cell line whose REV7 is
      overexpressed. Taken together, these results contributed to a recognition of the
      oncogene functions of REV7 in breast cancer cells and provided a novel direction
      to treat breast cancer.

PMID- 27712589
TI  - Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and
      Histone Acetylation in Renal Cancer Cells.
AB  - The histone deacetylase (HDAC) inhibitor belinostat increases the amount of
      unfolded proteins in cells by promoting the acetylation of heat shock protein 90
      (HSP90), thereby disrupting its chaperone function. The human immunodeficiency
      virus protease inhibitor ritonavir, on the other hand, not only increases
      unfolded proteins by suppressing HSP90 but also acts as a proteasome inhibitor.
      We thought that belinostat and ritonavir together would induce endoplasmic
      reticulum (ER) stress and kill renal cancer cells effectively. The combination of
      belinostat and ritonavir induced drastic apoptosis and inhibited the growth of
      renal cancer cells synergistically. Mechanistically, the combination caused ER
      stress (evidenced by the increased expression of the ER stress markers) and also
      enhanced histone acetylation by decreasing the expression of HDACs. To our
      knowledge, this is the first study that showed a beneficial combined effect of
      belinostat and ritonavir in renal cancer cells, providing a framework for testing
      the combination in renal cancer patients.

PMID- 27712590
TI  - Knockdown of Long Noncoding RNA uc.338 by siRNA Inhibits Cellular Migration and
      Invasion in Human Lung Cancer Cells.
AB  - Lung cancer remains a critical health concern worldwide. Long noncoding RNAs with
      ultraconserved elements have recently been implicated in human tumorigenesis. The
      present study investigated the role of ultraconserved element 338 (uc.338) in the
      regulation of cell proliferation and metastasis in human lung cancer. Our data
      showed that the expression of uc.338 in lung cancer was remarkably increased in
      vivo and in vitro. Depletion of uc.338 with specific siRNA interference retarded
      the cell proliferative rate in lung cancer cell lines NCI-H929 and H1688.
      Furthermore, knockdown of uc.338 caused cell cycle arrest in the G0/G1 phase in
      both cell lines. Transwell assays showed that inhibition of uc.338 notably
      decreased migration and invasion in NCI-H929 and H1688 cells. Moreover, uc.338
      depletion decreased the expression of cyclin B1, Cdc25C, Snail, vimentin, and N
      cadherin while increasing the protein level of E-cadherin, shown with Western
      blot analysis. These results suggested the pro-oncogenic potential of uc.338 in
      lung cancer, which might provide novel clues for the diagnosis and treatment of
      lung cancer in the clinic.

PMID- 27712591
TI  - MicroRNA-16-1 Inhibits Tumor Cell Proliferation and Induces Apoptosis in A549 Non
      Small Cell Lung Carcinoma Cells.
AB  - Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Plenty
      of microRNAs (miRs), except miR-16-1, have been reported to be associated with
      the initiation and progression of NSCLC. This study was aimed to explore the
      impacts of miR-16-1 on NSCLC cells. Human NSCLC cell line A549 was used, and the
      expression of miR-16-1 was up- or downregulated by transfecting with miR-16-1
      mimics or inhibitors. Afterward, cell proliferation and apoptosis were detected
      using MTT assay, BrdU assay, and Annexin V/FITC Apoptosis Detection Kit. The
      expression changes of proliferation- and apoptosis-related factors were measured
      by Western blot. Results showed that miR-16-1 overexpression significantly
      inhibited cell proliferation and induced apoptosis when compared with the control
      group. Besides, miR-16-1 overexpression significantly upregulated the protein
      expressions of p27, Bax, procaspase 3, and cleaved caspase 3, whereas it
      downregulated Bcl-2. Conversely, miR-16-1 suppression affected NSCLC cell
      proliferation and apoptosis, and these protein expressions resulted in completely
      opposite impacts. In conclusion, miR-16-1 overexpression could inhibit cell
      proliferation and induce apoptosis via regulating the expression of p27, Bcl-2,
      Bax, and caspase 3 in NSCLC cells.

PMID- 27712592
TI  - Suppressive Role of MicroRNA-148a in Cell Proliferation and Invasion in Ovarian
      Cancer Through Targeting Transforming Growth Factor-beta-Induced 2.
AB  - Ovarian cancer (OC) is one of the most common gynecological malignancies.
      MicroRNAs (miRs) play a crucial role in the development and progression of OC,
      but the underlying mechanism remains largely unclear. Our study investigated the
      regulatory role of miR-148a in OC cell proliferation and invasion. We found that
      miR-148a was significantly downregulated in OC tissues compared to their matched
      adjacent nontumor tissues. In addition, its expression was also reduced in OC
      cell lines (SKOV3, ES-2, OVCAR, and A2780) compared to normal ovarian epithelial
      cells. Overexpression of miR-148a caused a significant decrease in OC cell
      proliferation and invasion, as well as reduced MMP9 protein levels. Transforming
      growth factor-beta-induced 2 (TGFI2) was further identified as a target gene of
      miR-148a, and its protein expression was downregulated in OC cells after miR-148a
      overexpression. Restoration of TGFI2 attenuated the suppressive effects of miR
      148a on OC cell proliferation and invasion. Moreover, we found that TGFI2 was
      remarkably upregulated in OC tissues when compared with their matched adjacent
      nontumor tissues, and observed a reverse correlation between miR-148a and TGFI2
      expression in OC tissues. On the basis of these findings, we suggest that miR
      148a inhibits OC cell proliferation and invasion partly through inhibition of
      TGFI2. Therefore, our study highlights the importance of the miR-148a/TGFI2 axis
      in the malignant progression of OC.

PMID- 27712593
TI  - Knockdown of UBE2T Inhibits Osteosarcoma Cell Proliferation, Migration, and
      Invasion by Suppressing the PI3K/Akt Signaling Pathway.
AB  - Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the E2 family, was found to
      be overexpressed in a great many cancers such as bladder cancer, lung cancer, and
      prostate cancer. However, there have been no reports on the role of UBE2T in
      osteosarcoma. In this study, we tried to make the effects of UBE2T on
      osteosarcoma clear. The study results showed that UBE2T was overexpressed in
      osteosarcoma tissues and cell lines. Moreover, UBE2T knockdown inhibited
      osteosarcoma cell proliferation, migration, and invasion. We also observed that
      UBE2T downregulation could suppress the activity of the PI3K/Akt signaling
      pathway. Therefore, we concluded that UBE2T exerted its inhibitory effects on
      osteosarcoma cells via suppressing the PI3K/Akt signaling pathway. These findings
      indicated that UBE2T may be a potential therapeutic target for osteosarcoma
      treatment.

PMID- 27712594
TI  - MicroRNA-21 Regulates the Proliferation, Differentiation, and Apoptosis of Human
      Renal Cell Carcinoma Cells by the mTOR-STAT3 Signaling Pathway.
AB  - MicroRNA-21 (miRNA-21), a kind of short, noncoding RNAs, functioned as a tumor
      marker and was upregulated in renal cell carcinoma (RCC). However, the underlying
      mechanisms of miRNA-21 in RCC were uncertain. Therefore, the effects and
      mechanisms of miRNA-21 on the proliferation, differentiation, and apoptosis of
      cultured human RCC cells were further investigated in this study. After slicing
      miRNA-21 in RCC cells, the viability, mRNA expression of C/EBPalpha and
      PPARgamma, caspase 3 activity, and protein expression of mTOR, STAT3, and pSTAT3
      were determined. It was found that knockdown of miRNA-21 downregulated the
      optical density (OD) value of cells, inhibited mRNA expression of PPARgamma and
      C/EBPalpha, and enhanced activity of caspase 3. Furthermore, protein expression
      of pSTAT3 was also decreased in the absence of miRNA-21. Notably, miRNA-21
      changed proliferation, differentiation, and apoptosis of human RCC cells were
      partially regulated following the block of the mTOR-STAT3 signaling pathway by
      the mTOR inhibitor (XL388). It was indicated that miRNA-21 promoted proliferation
      and differentiation and decreased apoptosis of human RCC cells through the
      activation of the mTOR-STAT3 signaling pathway.

PMID- 27712595
TI  - Armadillo Repeat-Containing Protein 8 (ARMC8) Silencing Inhibits Proliferation
      and Invasion in Osteosarcoma Cells.
AB  - Armadillo repeat-containing protein 8 (ARMC8) plays an important role in
      regulating cell migration, proliferation, tissue maintenance, signal
      transduction, and tumorigenesis. However, the expression pattern and role of
      ARMC8 in osteosarcoma are still unclear. In this study, our aims were to examine
      the effects of ARMC8 on osteosarcoma and to explore its underlying mechanism. Our
      results demonstrated that ARMC8 was overexpressed in osteosarcoma cell lines.
      Knockdown of ARMC8 significantly inhibited osteosarcoma cell proliferation in
      vitro and markedly inhibited xenograft tumor growth in vivo. ARMC8 silencing also
      suppressed the epithelial-mesenchymal transition (EMT) phenotype, as well as
      inhibited the migration and invasion of osteosarcoma cells. Furthermore,
      knockdown of ARMC8 obviously inhibited the expression of beta-catenin, c-Myc, and
      cyclin D1 in MG-63 cells. In conclusion, this report demonstrates that ARMC8
      silencing inhibits proliferation and invasion of osteosarcoma cells. Therefore,
      ARMC8 may play an important role in the development and progression of human
      osteosarcoma and may represent a novel therapeutic target in the treatment of
      osteosarcoma.

PMID- 27712596
TI  - MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN
      Expression.
AB  - Gastric carcinoma is one of the most common malignancies in men, and microRNA
      plays a critical role in regulating the signaling networks of gastric carcinoma
      tumorigenesis and metastasis. We first report the functional characteristics of
      miR-221-3p in gastric carcinoma. Quantification in gastric carcinoma cell lines
      and tumor samples reveals significantly increasing miR-221-3p expression.
      Moreover, a high level of miR-221-3p is correlated with a poor prognosis for
      gastric carcinoma patients. Ectopic miR-221-3p expression significantly promotes
      gastric carcinoma cell proliferation, invasion, and sphere formation, while
      silencing miR-221-3p significantly inhibits these abilities in gastric carcinoma
      cells. Tests in vivo showed that miR-221-3p significantly promotes tumor growth
      in xenograft mouse models. In this study, we reveal that miR-221-3p targets PTEN
      mRNA and downregulates PTEN, which is the possible mechanism of miR-221-3p
      induced oncogenic properties. Collectively, we reveal a critical role for miR-221
      3p in gastric carcinoma development and progression.

PMID- 27712597
TI  - Knockdown of Latent Transforming Growth Factor-beta (TGF-beta)-Binding Protein 2
      (LTBP2) Inhibits Invasion and Tumorigenesis in Thyroid Carcinoma Cells.
AB  - Latent transforming growth factor-beta (TGF-beta)-binding protein 2 (LTBP2) is
      one of four proteins in the LTBP family of proteins (LTBP1-4) and was shown to
      play a vital role in tumorigenesis. However, little is known regarding the
      functional role of LTBP2 in thyroid carcinoma. Therefore, the current study aimed
      to evaluate the effect of LTBP2 expression on the proliferation, invasion, and
      tumorigenesis in thyroid carcinoma cells and to explore the molecular mechanism
      of LTBP2 in tumor progression. Our results showed that the expression of LTBP2 is
      upregulated in human thyroid carcinoma and cell lines. Knockdown of LTBP2
      inhibits the proliferation, invasion, and EMT phenotype in thyroid carcinoma
      cells. Furthermore, knockdown of LTBP2 attenuates thyroid carcinoma growth in
      nude mice. Finally, knockdown of LTBP2 inhibits activation of the PI3K/Akt
      pathway in thyroid carcinoma cells. In summary, the present study has provided
      further evidence that knockdown of LTBP2 inhibits invasion and tumorigenesis in
      thyroid carcinoma cells. Our findings may help to further elucidate the molecular
      mechanisms underlying thyroid carcinoma progression and provide candidate targets
      for the prevention and treatment of thyroid carcinoma.

PMID- 27712599
TI  - Exosomes Derived From Hypoxic Colorectal Cancer Cells Promote Angiogenesis
      Through Wnt4-Induced beta-Catenin Signaling in Endothelial Cells.
AB  - Cancer cell-derived exosomes have been actively released into the tumor
      microenvironment with pleiotropic roles in tumor growth and metastasis, including
      angiogenesis and immune modulation. However, the functions and underlying
      mechanisms of exosomes shed by colorectal cancer (CRC) cells under hypoxic
      conditions remain unknown. Here we found that exosomes derived from hypoxic CRC
      cells promoted the proliferation and migration of endothelial cells. Suppression
      of exosome secretion through RAB27a knockdown in CRC cells inhibited exosomal
      induced proliferation and migration of endothelial cells. Furthermore, we
      discovered that these exosomes enriched with Wnt4 were dependent on HIF1alpha.
      Exosomal Wnt4 increased beta-catenin nuclear translocation in endothelial cells.
      The induction of beta-catenin signaling is critical for the proliferation and
      migration of endothelial cells, which could be abolished by the inhibitor ICG001.
      The in vivo animal study further revealed the tumor-promoting effects of CRC cell
      derived exosomes with enhanced tumor growth and angiogenesis. Taken together, our
      study indicates that CRC cells promote angiogenesis through exosome-mediated
      Wnt/beta-catenin signaling in endothelial cells under hypoxia, which might be a
      new mechanism in CRC development.

PMID- 27712600
TI  - Empty Spiracles Homeobox 2 (EMX2) Inhibits the Invasion and Tumorigenesis in
      Colorectal Cancer Cells.
AB  - Empty spiracles homeobox 2 (EMX2) is a homeodomain-containing transcription
      factor that plays an essential role in tumorigenesis. However, to the best of our
      knowledge, the role of EMX2 in human colorectal cancer (CRC) is still unclear.
      Thus, the aim of this study was to investigate the expression and role of EMX2 in
      CRC. Our results demonstrated that the expression of EMX2 was greatly decreased
      in CRC tissues and cell lines. Overexpression of EMX2 significantly inhibited the
      proliferation in vitro and CRC tumor growth in nude mice. In addition, EMX2 also
      inhibited the migration and invasion of CRC cells. Mechanically, overexpression
      of EMX2 downregulated the expression levels of beta-catenin, cyclin D1, and c-Myc
      in CRC cells. Taken together, our study demonstrates that EMX2 inhibits
      proliferation and tumorigenesis through inactivation of the Wnt/beta-catenin
      pathway in CRC cells. Therefore, EMX2 may be a potential therapeutic target for
      the treatment of CRC.

PMID- 27712601
TI  - The Quality Measurement Crisis: An Urgent Need for Methodological Standards and
      Transparency.

PMID- 27712602
TI  - Consumer Rankings and Health Care: Toward Validation and Transparency.
AB  - BACKGROUND: Differences between the Centers for Medicare & Medicaid Services
      (CMS)-measured rates of safety events for Rush University Medical Center (RUMC;
      Chicago) and the U. S. News & World Report (USNWR)-deter mined patient safety
      score were evaluated in an attempt to validate the USNWR patient safety score
      based ranking. METHODS: The USNWR findings for Patient Safety Indicators (PSIs)
      were compared with findings derived from RUMC internal billing data, and
      sensitivity analyses were conducted using a simulated data set derived from the
      Healthcare Cost and Utilization Project (HCUP) state inpatient data sets.
      RESULTS: Discrepancies were found for PSIs 3 (Pressure Ulcer Rate), 9
      (Perioperative Hemorrhage or Hematoma Rate), and 11 (Postoperative Respiratory
      Failure Rate)-an excess of 0.72, 0.63, and 0.26 cases/1,000 admissions, in USNWR
      versus RUMC, respectively). The sensitivity analysis, which included missing
      present on admission (POA) flags and dates, resulted in an increase of rates by
      1.83 (95% confidence interval [CI] = 1.10-2.56) cases/1,000 hospital- izations,
      2.72 (CI = 0.00-5.90) cases/1,000 hospitalizations, and 3.89 (CI = 1.60-6.20)
      cases/1,000 hospitalizations for PSI 3, 9, and 11, respectively. Regression
      modeling showed that each 1% increase in transfers was associated with an in-
      crease of 0.06 cases of PSI 3/1,000 admissions; each 1,000 increase in admissions
      was associated with an increase of 0.04 cases of PSI 9/1,000 admissions.
      CONCLUSION: The USNWR data set produced inaccurate PSI rates for RUMC, and false
      positive event rates were more common among high-transfer and high-volume hos-
      pitals. More transparency and validation is needed for con- sumer-based
      benchmarking methods. In response to these findings and concerns raised by
      others, in 2016 USNWR made changes to its methodology and data sources and
      reported them in announcing its 2016-17 Best Hospitals.

PMID- 27712604
TI  - A New Performance Improvement Model: Adding Benchmarking to the Analysis of
      Performance Indicator Data.
AB  - BACKGROUND: A performance improvement model was developed that focuses on the
      analysis and interpretation of performance indicator (PI) data using statistical
      process control and benchmarking. PIs are suitable for comparison with benchmarks
      only if the data fall within the statistically accepted limit-that is, show only
      random variation. Specifically, if there is no significant special-cause
      variation over a period of time, then the data are ready to be benchmarked.
      METHODS: The proposed Define, Measure, Control, Internal Threshold, and Benchmark
      model is adapted from the Define, Measure, Analyze, Improve, Control (DMAIC)
      model. The model consists of the following five steps: Step 1. Define the
      process; Step 2. Monitor and measure the variation over the period of time; Step
      3. Check the variation of the process; if stable (no significant variation), go
      to Step 4; otherwise, control variation with the help of an action plan; Step 4.
      Develop an internal threshold and compare the process with it; Step 5.1. Compare
      the process with an internal benchmark; and Step 5.2. Compare the process with an
      external benchmark. RESULTS: The steps are illustrated through the use of health
      care-associated infection (HAI) data collected for 2013 and 2014 from the
      Infection Control Unit, King Fahd Hospital, University of Dammam, Saudi Arabia.
      CONCLUSION: Monitoring variation is an important strategy in understanding and
      learning about a process. In the example, HAI was monitored for variation in
      2013, and the need to have a more predictable process prompted the need to
      control variation by an action plan. The action plan was successful, as noted by
      the shift in the 2014 data, compared to the historical average, and, in addition,
      the variation was reduced. The model is subject to limitations: For example, it
      cannot be used without benchmarks, which need to be calculated the same way with
      similar patient populations, and it focuses only on the "Analyze" part of the
      DMAIC model.

PMID- 27712603
TI  - Viewing Prevention of Catheter-Associated Urinary Tract Infection as a System:
      Using Systems Engineering and Human Factors Engineering in a Quality Improvement
      Project in an Academic Medical Center.
AB  - BACKGROUND: Urinary tract infections (UTIs) are the most commonly reported health
      care-associated infection (HAI) in the United States. Among UTIs acquired in the
      hospital, approximately 75% are associated with urinary catheters, with an
      estimated 15%-25% of all hospitalized patients receiving urinary catheters during
      their hospitalization. Despite ambitious national goals to reduce these
      infections, catheter-associated urinary tract infection (CAUTI) has not decreased
      in the United States. METHODS: Systems engineering (SE) and human factors engi-
      neering (HFE) methods were used to reduce urinary catheter utilization and CAUTIs
      in a three-year (June 1, 2012-May 31, 2015) quality improvement project in a 610
      bed academic medical center. These methods were used to define the factors
      leading to CAUTI and promote standardization of urinary catheter utilization,
      insertion, and maintenance. RESULTS: The total systemwide CAUTI count decreased
      from 135 cases at baseline to 74 cases at the end of the project's Year 1, to 59
      cases at the end of Year 2, and 25 cases at the end of Year 3-alone, an 81.5%
      reduction from baseline. The control chart showed a steady decline in the CAUTI
      count within a few months after the project's start. By the end of Year 3, on the
      basis of an average attributable-per-patient cost of CAUTI ($1,007 per case), the
      estimated annual avoidable CAUTI costs decreased from approximately $135,945 to
      $25,175 per year. Urinary catheter utilization decreased by 27.3% during the same
      three-year period, and the systemwide CAUTI standardized infection ratio (SIR)
      decreased from 3.2 to 0.51 (84.1% from baseline). CONCLUSION: SE and HFE methods
      and principles can effectively decrease urinary catheter utilization and CAUTI
      incidence in an academic medical center hospital environment.

PMID- 27712605
TI  - Creating a Professional Ladder for Interpreters for Improvement of Care.
AB  - BACKGROUND: Children's Hospital Los Angeles (CHLA), a metropolitan academic
      medical center, recognized limitations in how the professional interpreters from
      the Diversity Services Department were used to support effective patient-provider
      communication across the organization. Given the importance of mitigating
      language and communication barriers, CHLA sought to minimize clinical and
      structural barriers to health care for limited English proficiency populations
      through a comprehensive restructuring of the Diversity Services Department. This
      approach entailed a new delivery model for hospital language assistance and
      cultural consultancy resources. METHODS: The intervention focused on
      restructuring the Diversity Services Department, redefining priorities,
      reallocating resources, and redefining the roles of the language staff positions
      in the department. The language staff role was redesigned to fit a four-level
      professional career ladder modeled after the professional career ladders commonly
      used in hospitals for the RN role and other professional disciplines. The
      approach involved creating new levels of language specialist, each with
      progressive requirements for performance, leadership, and accountability for
      patient care outcomes. Language staff in the inpatient, clinic, and emergency
      department settings worked alongside nurses, physicians, and other disciplines to
      care for a specific set of patients. RESULTS: The result of this work was a
      positive culture change resulting in service efficiencies, care improvements, and
      improved access to language services. CONCLUSIONS: A professional career ladder
      for language staff contributed to improving the quality and access of language
      services and advancing the interpreting profession by incorporating care
      coordination support, vital document translation, and cultural consultancy.

PMID- 27712606
TI  - Using Human Factors Design Principles and Industrial Engineering Methods to
      Improve Accuracy and Speed of Drug Selection with Medication Trays.

PMID- 27712607
TI  - Letters to the Editor.

PMID- 27712610
TI  - Contextual factors in geosocial-networking smartphone application use and
      engagement in condomless anal intercourse among gay, bisexual, and other men who
      have sex with men who use Grindr.
AB  - : Background Geosocial-networking smartphone applications (apps) have been used
      increasingly by men who have sex with men (MSM) to meet new sexual partners. The
      purpose of this study was to examine associations between contexts of app use
      (e.g. using apps when drinking) and condomless anal intercourse among a sample of
      MSM who use these apps. METHODS: MSM (n=174) in New York City were recruited
      through Grindr, a geosocial-networking app popular among MSM, using broadcast
      advertisements asking MSM to complete an Internet-based survey about their app
      use and sexual behaviours. Log-binomial regression models were fit to assess the
      association between each of the six app-use contexts (e.g. using apps when
      lonely, when drinking) and engagement in condomless insertive and receptive anal
      intercourse with one or more partners in the past 3 months. RESULTS: Engagement
      in condomless receptive and insertive anal intercourse with one or more partners
      in the preceding 3 months was common (39.7% and 43.1% respectively) and was
      associated with several app-use contexts. For example, significant associations
      (P<0.05) were observed between alcohol and other drug use when using these apps
      and engagement in condomless receptive and insertive anal intercourse.
      CONCLUSION: Given that 57.5% of respondents had engaged in condomless anal
      intercourse in the preceding 3 months and the associations of app-use contexts
      with condomless sexual behaviours, these findings suggest that reductions in
      substance use may lead to safer sexual practices among MSM who use apps to meet
      sexual partners.

PMID- 27712611
TI  - Social participation as an indicator of successful aging: an overview of concepts
      and their associations with health.
AB  - Objectives Social participation has generated a wealth of research in
      gerontology, but the concept suffers from a lack of conceptual clarity that
      renders it difficult to define and measure. This means that research on social
      participation is difficult to compare directly. The aim of the present study was
      to draw the literature on social participation in older adults together to inform
      health services researchers seeking to investigate social participation as an
      indicator of successful aging. Methods A narrative review of studies
      investigating the association between social participation and health in adults
      aged 65 years and older was conducted. Results Three concepts of social
      participation (i.e. social connections, informal social participation and
      volunteering) were defined, their measurement instruments described and evidence
      of their associations with health explored. All three concepts have demonstrated
      associations with an array of health indicators. Prospective studies reveal that
      social participation at baseline is positively associated with mental and
      physical health. Conclusion A model of social participation on health is
      presented, showing the evidence that all three concepts contribute to the
      association between social participation and health through their shared
      mechanisms of social support and social cohesion with the wider community. Using
      an instrument that can be separated into these three distinct concepts will
      assist health services researchers to determine the relative effect of each form
      of participation on the health of older adults. What is known about the topic?
      Social participation has generated a wealth of research in gerontology. The scope
      of the literature on social participation is broad and the concepts diverse. For
      this reason, most previous systematic reviews have been unable to comprehensively
      assess the effect of all concepts of social participation on health. This means
      the research on social participation is difficult to compare directly, and
      indicators of social participation in older adults are difficult for policy
      makers to select. What does this paper add? This paper overviews the three
      concepts of social participation, their methods of measurement and their
      associations with health in older adults. We present a model of social
      participation that incorporates all three concepts of social participation and
      their effects on health. We argue that the use of a measure that can be segmented
      into each of the three forms of social participation will predict more of the
      variance in health outcomes than any measure on its own. What are the
      implications for practitioners? Enhancing the social participation of older
      adults is a key factor in successful aging that many older adults value. However,
      many service provision organisations tend to focus on meeting the specific
      physical needs of clients, rather than targeting services that connect older
      adults with their community. Targeting social participation may present one of
      the greatest opportunities to improve older adults' general health, and will also
      generate societal benefits by increasing community contributions from this group.
      Selecting an indicator of social participation that measures each of the three
      concepts overviewed in this paper will enable policy makers to identify the areas
      in which social interventions for older adults will have the most effect.

PMID- 27712612
TI  - Prevalence of oral human papillomavirus in men attending an Italian sexual health
      clinic.
AB  - A high-risk population, formed by 79 consecutive male attendees of our sexually
      transmissible infections clinic, and who did not have any overt signs of human
      papillomavirus (HPV) infection, were examined. Oral HPV prevalence (37%) was much
      higher than previously reported. Periurethral HPV-DNA was found in 49% of the
      patients and anal HPV-DNA was found in 43% of the patients. Considering the high
      prevalence of oral HPV obtained in the current study, it is important to further
      investigate the burden of oral HPV, not only in men who have sex with men, but
      also in heterosexual men and in women.

PMID- 27712613
TI  - Exploring attitudes towards sexting of young people: a cross-sectional study.
AB  - : Background Sexting is a common emerging phenomenon. This study aims to explore
      young people's attitudes towards sexting. METHODS: Participants (n=469, age range
      15-29 years) were recruited at a music festival and self-completed a
      questionnaire. Attitudes towards sexting were assessed using a series of seven
      statements, rated on a five-point Likert scale from 'strongly agree' to 'strongly
      disagree'. Correlates of sexting attitudes were determined using multivariable
      regression. RESULTS: Forty-six percent of respondents reported ever sexting. Most
      (88%) agreed 'It's risky for a girl to send a naked picture of herself,' fewer
      agreed with the statement 'It's risky for a boy to send a naked picture of
      himself' (77%). Thirty percent agreed that 'If someone I'd just started seeing
      sent me a sext I might show it to some friends,' however, only 14% might do the
      same with a sext from a boyfriend or girlfriend (this did not differ by sex).
      More permissive attitudes to sexting were associated with being male, lower
      sexual health knowledge, inconsistent condom use with casual partners, and higher
      alcohol consumption. CONCLUSIONS: Although the majority of young people surveyed
      agreed that sexting was risky it was a common practice. Given the potential
      psychosocial impact of sharing sexts without consent, it was concerning that up
      to a third of participants indicated they might do so. The findings of this study
      have implications for informing education on sexting.

PMID- 27712614
TI  - Seasonal variation in gonorrhoea incidence among men who have sex with men.
AB  - : Background After reviewing urethral gonorrhoea cases among men who have sex
      with men (MSM) at the South Australia Specialist Sexual Health (SASSH) in
      Adelaide, Australia, we noticed peaks of gonorrhoea among MSM occurred
      predominantly in the first quarter of the year (January-March). The aim of this
      study was to formally test this hypothesis against data from a similar period at
      three sexual health services, one each in Adelaide, Melbourne and Sydney.
      METHODS: This study was a retrospective analysis of computerised records at the
      three Australian sexual health services. Potential risk factors for urethral
      gonorrhoea among MSM were also reviewed at the SASSH. RESULTS: More peaks of
      gonorrhoea cases were observed in the first quarter of the year in Adelaide and
      Sydney and in the second and fourth quarter in Melbourne. Factors independently
      associated with urethral gonorrhoea at the SASSH were being a young MSM,
      especially those aged 25-29 (odds ratio (OR) 2.66, 95% confidence interval (CI):
      2.00-3.54), having more than one sexual partner (OR 1.71, 95% CI: 1.43-2.04),
      having had sex interstate and overseas (OR 1.52, 95% CI: 1.06-2.17), and
      presenting in the first quarter (OR 1.30, 95% CI: 1.10-1.55). CONCLUSION: Our
      data suggest that gonorrhoea among MSM occurs in a seasonal pattern, particularly
      late summer into early autumn. This has implications for the provision of health
      services over the year and for the timing of health promotion activities.

PMID- 27712615
TI  - Integration of nurse practitioners using a change management framework: the way
      forward.
AB  - Objective The aim of the present study was to investigate and describe the
      application of a change management theoretical framework in relation to nurse
      practitioner (NP) role integration. Methods A survey formed Phase 1 of a broader
      mixed-methods study to explore perceptions of the change process involved with
      integrating NPs into Australian health care settings. The stakeholder
      participants were NPs, nurse managers and nurse policy advisers. Results Key
      themes were identified adding information about how NPs, nurse managers and nurse
      policy advisers perceive the integration of NPs into Australian healthcare. The
      themes correlate to the components of organisational change management necessary
      to embed NPs into the healthcare workforce. Conclusions Healthcare reform is a
      complex organisational change. Alignment of several key elements is required for
      the process to be successful. A change management proposal for reframing
      organisations provides an apt framework for use in the Australian context of
      reforming workforce to integrate NPs into healthcare teams. The theoretical
      framework proposes that multiple lenses be applied to change processes, to
      integrate NPs into the workforce and highlights the need for exceptional
      leadership throughout such endeavours. What is known about the topic? NPs provide
      safe and efficient care to patients, often in settings where access to health
      care is limited. NPs have been identified as a key strategic workforce reform
      initiative to address some of the known healthcare gaps. What does this paper
      add? This paper adds information about how NPs, nurse managers and nurse policy
      advisers perceive progress of the integration of NPs into healthcare settings.
      The findings are contextualised within an organisational change framework and
      highlight the complexity of healthcare reform. What are the implications for
      practitioners? The findings provide a novel approach for managing workforce
      reform and identify the components of change management necessary to embed NPs
      into the healthcare workforce.

PMID- 27712616
TI  - The future of drugs: recreational drug use and sexual health among gay and other
      men who have sex with men.
AB  - There are complex historical connections between sexual minoritisation and
      desires to chemically alter bodily experience. For gay men, drug and alcohol use
      can be a creative or experimental response to social marginalisation - and not
      necessarily a problematic one in every instance. Numerous studies have found that
      infection with HIV and other sexually transmissible infections (STIs) is more
      likely among gay and men who have sex with men (MSM) who use recreational drugs
      than those who do not, but the causal nature of these relations is uncertain.
      Sexualised drug use is associated with a range of other problems, including
      dependence, mental health issues, accident and overdose. A growing body of work
      in the Alcohol and Other Drugs (AOD) field demonstrates the action of drugs and
      their purported effects to be a product of their relations with various other
      actors, contexts and practices. Given these contingencies, it is impossible to
      predict the future of drugs or their effect on the sexual health of gay and MSM
      with any degree of certainty. This article outlines some of the conditions most
      likely to mediate such futures in the medium term. Public funding for lesbian,
      gay, bisexual, transgender and queer drug issues should not remain restricted to
      questions of HIV prevention and sexual health. It should be expanded to equip
      sexual health and AOD service providers with the cultural and sexual literacy to
      mitigate stigma and allow them to respond constructively to drug problems among
      sexual and gender minorities as a matter of priority.

PMID- 27712617
TI  - What is the extent of repeat prescriptions for post-exposure prophylaxis for HIV
      after sexual exposure among men who have sex with men in the UK?
AB  - People who repeatedly present for post-exposure prophylaxis (PEP) for prevention
      of HIV following a high-risk sexual exposure are of concern according to the
      British HIV Association PEP guidelines. The aim of this audit was to determine
      the extent of repeat PEP prescriptions for men who have sex with men (MSM) by
      conducting a retrospective review of patient notes from a 5-year period at one
      genitourinary medicine clinic. Over the 5 years, 107 of 929 MSM (11.5%; 95%
      confidence interval: 9.45-13.55) received more than one PEP prescription (repeat
      range 1-8; mean=3.3, s.d.=1.44). Forty percent of these had received three or
      more PEP prescriptions. Seven of the 107 became HIV positive. Patients need to be
      offered and encouraged to take up behavioural risk reduction interventions at the
      time of each PEP prescription.

PMID- 27712618
TI  - Sexual transmission of hepatitis C virus among gay and bisexual men: a systematic
      review.
AB  - A systematic review was performed on the evidence of sexual transmission of
      hepatitis C virus (HCV) in gay and bisexual men (GBM). Studies conducted in
      industrialised countries and published in English from 2000 to 2015 with data on
      HCV in GBM were included. Pooled estimates of prevalence and incidence of HCV
      infection were stratified by study settings and participants' HIV status using
      random effect models. Case-series reports were summarised descriptively. Of the
      38 cross-sectional studies, the pooled HCV prevalence was substantially higher in
      HIV-positive men (8.3%, 95% CI: 6.7-9.9) than in HIV-negative men (1.5%, 95% CI
      0.8-2.1), and higher in those who reported injecting drug use (34.8%, 95% CI 26.9
      42.7) than in those who did not (3.5%, 95% CI 2.4-4.5). Of the 16 longitudinal
      studies, the pooled HCV incidence was markedly higher in clinic-based (7.0 per
      1000 person-years, 95% CI 4.6-9.5) than in community-based (1.4 per 1000 person
      years, 95% CI 0.7-2.1) studies, and in HIV-positive men (6.4 per 1000 person
      years, 95% CI 4.6-8.1) than in HIV-negative men (0.4 per 1000 person-years, 95%
      CI 0-0.9). Since the early 2000s, 15 case-series reports increasingly pointed to
      the importance of sexual transmission of HCV in mainly HIV-positive men.
      Injecting drug use remained the major transmission route of HCV in GBM. Receptive
      condomless intercourse and concurrent ulcerative sexually transmissible
      infections are likely drivers that facilitated HCV sexual transmission in HIV
      positive men. HCV incidence remains very low in HIV-negative GBM.

PMID- 27712619
TI  - Organizing graduate medical education programs into communities of practice.
AB  - BACKGROUND: A new organizational model of educational administrative support was
      instituted in the Department of Medical Education (DME) to better meet increasing
      national accreditation demands. Residency and fellowship programs were organized
      into four 'Communities of Practice' (CoOPs) based on discipline similarity,
      number of learners, and geographic location. Program coordinator reporting lines
      were shifted from individual departments to a centralized reporting structure
      within the DME. The goal of this project was to assess the impact on those most
      affected by the change. METHODS: This was a mixed methods study that utilized
      structured interviews and the Organizational Culture Assessment Instrument
      (OCAI). Eleven members of the newly formed CoOPs participated in the study.
      RESULTS: Three major themes emerged after review and coding of the interview
      transcripts: improved group identity, improved availability of resources, and
      increased opportunity for professional growth. OCAI results indicated that
      respondents are committed to the DME and perceived the culture to be empowering.
      The 'preferred culture' was very similar to the culture at the time of the study,
      with some indication that DME employees are ready for more creativity and
      innovation in the future. CONCLUSION: Reorganization within the DME of residency
      programs into CoOPs was overwhelmingly perceived as a positive change. Improved
      resources and accountability may position our DME to better handle the increasing
      complexity of graduate medical education.

PMID- 27712621
TI  - Supramolecular Architecture of the Coronavirus Particle.
AB  - Coronavirus particles serve three fundamentally important functions in infection.
      The virion provides the means to deliver the viral genome across the plasma
      membrane of a host cell. The virion is also a means of escape for newly
      synthesized genomes. Lastly, the virion is a durable vessel that protects the
      genome on its journey between cells. This review summarizes the available X-ray
      crystallography, NMR, and cryoelectron microscopy structural data for coronavirus
      structural proteins, and looks at the role of each of the major structural
      proteins in virus entry and assembly. The potential wider conservation of the
      nucleoprotein fold identified in the Arteriviridae and Coronaviridae families and
      a speculative model for the evolution of corona-like virus architecture are
      discussed.

PMID- 27712620
TI  - The experiences of patients with Duchenne muscular dystrophy in facing and
      learning about their clinical conditions.
AB  - Patients experience extreme difficulty when facing an intractable genetic
      disease. Herein, we examine the experiences of patients with Duchenne muscular
      dystrophy in facing and learning about their disease. A total of seven patients
      with Duchenne muscular dystrophy (age range: 20-48) participated. We conducted in
      depth interviews with them about how they learned of their disease and how their
      feelings regarding the disease changed over time. Transcribed data were analysed
      using thematic analysis. The following themes emerged from this analysis:
      "experiences before receiving the diagnosis," "experiences when they learned of
      their condition and progression of the disease," "supports," and "desired
      explanations." Anxiety and worry were most pronounced when they had to transition
      to using wheelchairs or respirators due to disease progression; indeed, such
      transitions affect the patients psychological adjustment. In such times, support
      from significant others in their lives helped patients adjust.

PMID- 27712622
TI  - Coronavirus cis-Acting RNA Elements.
AB  - Coronaviruses have exceptionally large RNA genomes of approximately 30 kilobases.
      Genome replication and transcription is mediated by a multisubunit protein
      complex comprised of more than a dozen virus-encoded proteins. The protein
      complex is thought to bind specific cis-acting RNA elements primarily located in
      the 5'- and 3'-terminal genome regions and upstream of the open reading frames
      located in the 3'-proximal one-third of the genome. Here, we review our current
      understanding of coronavirus cis-acting RNA elements, focusing on elements
      required for genome replication and packaging. Recent bioinformatic, biochemical,
      and genetic studies suggest a previously unknown level of conservation of cis
      acting RNA structures among different coronavirus genera and, in some cases, even
      beyond genus boundaries. Also, there is increasing evidence to suggest that
      individual cis-acting elements may be part of higher-order RNA structures
      involving long-range and dynamic RNA-RNA interactions between RNA structural
      elements separated by thousands of nucleotides in the viral genome. We discuss
      the structural and functional features of these cis-acting RNA elements and their
      specific functions in coronavirus RNA synthesis.

PMID- 27712624
TI  - Feline Coronaviruses: Pathogenesis of Feline Infectious Peritonitis.
AB  - Feline infectious peritonitis (FIP) belongs to the few animal virus diseases in
      which, in the course of a generally harmless persistent infection, a virus
      acquires a small number of mutations that fundamentally change its pathogenicity,
      invariably resulting in a fatal outcome. The causative agent of this deadly
      disease, feline infectious peritonitis virus (FIPV), arises from feline enteric
      coronavirus (FECV). The review summarizes our current knowledge of the genome and
      proteome of feline coronaviruses (FCoVs), focusing on the viral surface (spike)
      protein S and the five accessory proteins. We also review the current
      classification of FCoVs into distinct serotypes and biotypes, cellular receptors
      of FCoVs and their presumed role in viral virulence, and discuss other aspects of
      FIPV-induced pathogenesis. Our current knowledge of genetic differences between
      FECVs and FIPVs has been mainly based on comparative sequence analyses that
      revealed "discriminatory" mutations that are present in FIPVs but not in FECVs.
      Most of these mutations result in amino acid substitutions in the S protein and
      these may have a critical role in the switch from FECV to FIPV. In most cases,
      the precise roles of these mutations in the molecular pathogenesis of FIP have
      not been tested experimentally in the natural host, mainly due to the lack of
      suitable experimental tools including genetically engineered virus mutants. We
      discuss the recent progress in the development of FCoV reverse genetics systems
      suitable to generate recombinant field viruses containing appropriate mutations
      for in vivo studies.

PMID- 27712625
TI  - Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon
      Response.
AB  - Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome
      (MERS) are the most severe coronavirus (CoV)-associated diseases in humans. The
      causative agents, SARS-CoV and MERS-CoV, are of zoonotic origin but may be
      transmitted to humans, causing severe and often fatal respiratory disease in
      their new host. The two coronaviruses are thought to encode an unusually large
      number of factors that allow them to thrive and replicate in the presence of
      efficient host defense mechanisms, especially the antiviral interferon system.
      Here, we review the recent progress in our understanding of the strategies that
      highly pathogenic coronaviruses employ to escape, dampen, or block the antiviral
      interferon response in human cells.

PMID- 27712627
TI  - Coronavirus Spike Protein and Tropism Changes.
AB  - Coronaviruses (CoVs) have a remarkable potential to change tropism. This is
      particularly illustrated over the last 15 years by the emergence of two zoonotic
      CoVs, the severe acute respiratory syndrome (SARS)- and Middle East respiratory
      syndrome (MERS)-CoV. Due to their inherent genetic variability, it is inevitable
      that new cross-species transmission events of these enveloped, positive-stranded
      RNA viruses will occur. Research into these medical and veterinary important
      pathogens-sparked by the SARS and MERS outbreaks-revealed important principles of
      inter- and intraspecies tropism changes. The primary determinant of CoV tropism
      is the viral spike (S) entry protein. Trimers of the S glycoproteins on the
      virion surface accommodate binding to a cell surface receptor and fusion of the
      viral and cellular membrane. Recently, high-resolution structures of two CoV S
      proteins have been elucidated by single-particle cryo-electron microscopy. Using
      this new structural insight, we review the changes in the S protein that relate
      to changes in virus tropism. Different concepts underlie these tropism changes at
      the cellular, tissue, and host species level, including the promiscuity or
      adaptability of S proteins to orthologous receptors, alterations in the
      proteolytic cleavage activation as well as changes in the S protein
      metastability. A thorough understanding of the key role of the S protein in CoV
      entry is critical to further our understanding of virus cross-species
      transmission and pathogenesis and for development of intervention strategies.

PMID- 27712623
TI  - Viral and Cellular mRNA Translation in Coronavirus-Infected Cells.
AB  - Coronaviruses have large positive-strand RNA genomes that are 5' capped and 3'
      polyadenylated. The 5'-terminal two-thirds of the genome contain two open reading
      frames (ORFs), 1a and 1b, that together make up the viral replicase gene and
      encode two large polyproteins that are processed by viral proteases into 15-16
      nonstructural proteins, most of them being involved in viral RNA synthesis. ORFs
      located in the 3'-terminal one-third of the genome encode structural and
      accessory proteins and are expressed from a set of 5' leader-containing
      subgenomic mRNAs that are synthesized by a process called discontinuous
      transcription. Coronavirus protein synthesis not only involves cap-dependent
      translation mechanisms but also employs regulatory mechanisms, such as ribosomal
      frameshifting. Coronavirus replication is known to affect cellular translation,
      involving activation of stress-induced signaling pathways, and employing viral
      proteins that affect cellular mRNA translation and RNA stability. This chapter
      describes our current understanding of the mechanisms involved in coronavirus
      mRNA translation and changes in host mRNA translation observed in coronavirus
      infected cells.

PMID- 27712626
TI  - Molecular Basis of Coronavirus Virulence and Vaccine Development.
AB  - Virus vaccines have to be immunogenic, sufficiently stable, safe, and suitable to
      induce long-lasting immunity. To meet these requirements, vaccine studies need to
      provide a comprehensive understanding of (i) the protective roles of antiviral B
      and T-cell-mediated immune responses, (ii) the complexity and plasticity of major
      viral antigens, and (iii) virus molecular biology and pathogenesis. There are
      many types of vaccines including subunit vaccines, whole-inactivated virus,
      vectored, and live-attenuated virus vaccines, each of which featuring specific
      advantages and limitations. While nonliving virus vaccines have clear advantages
      in being safe and stable, they may cause side effects and be less efficacious
      compared to live-attenuated virus vaccines. In most cases, the latter induce long
      lasting immunity but they may require special safety measures to prevent
      reversion to highly virulent viruses following vaccination. The chapter
      summarizes the recent progress in the development of coronavirus (CoV) vaccines,
      focusing on two zoonotic CoVs, the severe acute respiratory syndrome CoV (SARS
      CoV), and the Middle East respiratory syndrome CoV, both of which cause deadly
      disease and epidemics in humans. The development of attenuated virus vaccines to
      combat infections caused by highly pathogenic CoVs was largely based on the
      identification and characterization of viral virulence proteins that, for
      example, interfere with the innate and adaptive immune response or are involved
      in interactions with specific cell types, such as macrophages, dendritic and
      epithelial cells, and T lymphocytes, thereby modulating antiviral host responses
      and viral pathogenesis and potentially resulting in deleterious side effects
      following vaccination.

PMID- 27712628
TI  - The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing.
AB  - Coronaviruses are animal and human pathogens that can cause lethal zoonotic
      infections like SARS and MERS. They have polycistronic plus-stranded RNA genomes
      and belong to the order Nidovirales, a diverse group of viruses for which common
      ancestry was inferred from the common principles underlying their genome
      organization and expression, and from the conservation of an array of core
      replicase domains, including key RNA-synthesizing enzymes. Coronavirus genomes
      (~26-32 kilobases) are the largest RNA genomes known to date and their expansion
      was likely enabled by acquiring enzyme functions that counter the commonly high
      error frequency of viral RNA polymerases. The primary functions that direct
      coronavirus RNA synthesis and processing reside in nonstructural protein (nsp) 7
      to nsp16, which are cleavage products of two large replicase polyproteins
      translated from the coronavirus genome. Significant progress has now been made
      regarding their structural and functional characterization, stimulated by
      technical advances like improved methods for bioinformatics and structural
      biology, in vitro enzyme characterization, and site-directed mutagenesis of
      coronavirus genomes. Coronavirus replicase functions include more or less
      universal activities of plus-stranded RNA viruses, like an RNA polymerase (nsp12)
      and helicase (nsp13), but also a number of rare or even unique domains involved
      in mRNA capping (nsp14, nsp16) and fidelity control (nsp14). Several smaller
      subunits (nsp7-nsp10) act as crucial cofactors of these enzymes and contribute to
      the emerging "nsp interactome." Understanding the structure, function, and
      interactions of the RNA-synthesizing machinery of coronaviruses will be key to
      rationalizing their evolutionary success and the development of improved control
      strategies.

PMID- 27712629
TI  - Preface.

PMID- 27712630
TI  - The Evolution of Physician Certification and the Canary in the Coal Mine.

PMID- 27712631
TI  - Role of Neuroinflammation in Parkinson Disease: The Enigma Continues.

PMID- 27712632
TI  - Physician Attitudes About Maintenance of Certification: A Cross-Specialty
      National Survey.
AB  - OBJECTIVES: To determine physicians' perceptions of current maintenance of
      certification (MOC) activities and to explore how perceptions vary across
      specialties, practice characteristics, and physician characteristics, including
      burnout. PATIENTS AND METHODS: We conducted an Internet and paper survey among a
      national cross-specialty random sample of licensed US physicians from September
      23, 2015, through April 18, 2016. The questionnaire included 13 MOC items, 2
      burnout items, and demographic variables. RESULTS: Of 4583 potential respondents,
      we received 988 responses (response rate 21.6%) closely reflecting the
      distribution of US physician specialties. Twenty-four percent of physicians (200
      of 842) agreed that MOC activities are relevant to their patients, and 15% (122
      of 824) felt they are worth the time and effort. Although 27% (223 of 834)
      perceived adequate support for MOC activities, only 12% (101 of 832) perceived
      that they are well-integrated in their daily routine and 81% (673 of 835)
      believed they are a burden. Nine percent (76 of 834) believed that patients care
      about their MOC status. Forty percent or fewer agreed that various MOC activities
      contribute to their professional development. Attitudes varied statistically
      significantly (P<.001) across specialties, but reflected low perceived relevance
      and value in nearly all specialties. Thirty-eight percent of respondents met
      criteria for being burned out. We found no association of attitudes toward MOC
      with burnout, certification status, practice size, rural or urban practice
      location, compensation model, or time since completion of training. CONCLUSION:
      Dissatisfaction with current MOC programs is pervasive and not localized to
      specific sectors or specialties. Unresolved negative perceptions will impede
      optimal physician engagement in MOC.

PMID- 27712633
TI  - Reduced Risk of Parkinson Disease in Patients With Rheumatoid Arthritis: A
      Nationwide Population-Based Study.
AB  - OBJECTIVE: To investigate the association between rheumatoid arthritis (RA) and
      the risk of developing Parkinson disease (PD). PATIENTS AND METHODS: This
      retrospective cohort study was conducted from January 1, 1998, through December
      31, 2010, using data from the Taiwan National Health Insurance Research Database.
      We identified 33,221 patients with newly diagnosed RA and 132,884 randomly
      selected age- and sex-matched patients without RA. A multivariable Cox
      proportional hazards regression model was used to evaluate the risk of developing
      PD in the RA cohort. RESULTS: The multivariable Cox proportional hazards
      regression analysis revealed an adjusted hazard ratio of 0.65 (95% CI, 0.58-0.73)
      for the development of PD in the RA cohort relative to the non-RA cohort. The
      cumulative incidence of PD was 2.42% lower in the RA cohort than in the non-RA
      cohort. The risk reduction of PD development in patients affected with RA was
      independent of treatment with disease-modifying antirheumatic drugs (DMARDs);
      subgroup analysis of patients treated with biologic DMARDs revealed further risk
      reduction (adjusted hazard ratio, 0.57; 95% CI, 0.41-0.79). CONCLUSION: Patients
      with RA have a reduced risk of developing PD. This risk reduction was independent
      of treatment with DMARDs; however, biologic DMARDs appear to further reduce this
      risk. Further research is necessary to explore the underlying mechanism.

PMID- 27712634
TI  - Systemic Immunoglobulin Light Chain Amyloidosis-Associated Myopathy:
      Presentation, Diagnostic Pitfalls, and Outcome.
AB  - OBJECTIVE: To characterize the natural history of immunoglobulin light chain
      amyloidosis-associated myopathy and to provide guidelines for recognition.
      PATIENTS AND METHODS: Fifty-one patients with systemic immunoglobulin light chain
      amyloidosis and biopsy-confirmed muscle amyloid deposition diagnosed between
      January 1, 1995, and December 31, 2015, were included in this study. RESULTS:
      Common presenting symptoms were muscle weakness in 49 patients (96%), dysphagia
      in 23 (45%), myalgia in 17 (33%), macroglossia in 17 (33%), jaw claudication in
      13 (25%), and hoarseness in 9 (18%). The median time from the onset of symptoms
      to diagnosis was almost 2 years. Less than two-thirds of the patients with an
      outside muscle biopsy (16 of 27) had an established pathologic confirmation of
      amyloidosis due to failure to routinely incorporate Congo red staining. Moreover,
      12 patients were incorrectly treated before diagnosis of amyloid myopathy. More
      than half of the patients had normal creatine kinase levels at diagnosis. Cardiac
      troponin T levels were elevated above the reference range in 5 of 12 patients who
      lacked evidence of cardiac involvement. Median overall survival was 32 months.
      Factors associated with inferior survival were involvement of more than 2 organs
      (median survival, 13 months), cardiac involvement (median survival, 15 months),
      and absence of stem cell transplant (median survival, 18 months). With the
      exclusion of patients treated with stem cell transplant, no improvement in
      survival was seen over the 1995-2004 and 2005-2015 decades. CONCLUSION:
      Immunoglobulin light chain amyloidosis-associated myopathy is rare. Delay in
      diagnosis is common, and there is a high rate of pathologic and clinical
      misdiagnosis. Awareness of elevation of cardiac troponin T levels in the absence
      of cardiac disease may be a clue to diagnosis.

PMID- 27712636
TI  - Diet Quality and Mortality Risk in Metabolically Obese Normal-Weight Adults.
AB  - OBJECTIVE: To examine the associations among the Dietary Approaches to Stop
      Hypertension (DASH)-style diet, the Healthy Eating Index (HEI), and mortality
      risk in metabolically obese normal-weight (MONW) adults. PATIENTS AND METHODS:
      Data were from normal-weight (body mass index of 18.5 to <25) adults aged 30 to
      90 years at baseline in the Third National Health and Nutrition Examination
      Survey, October 18, 1988, through October 15, 1994, followed up for deaths (all
      cause, cardiovascular, and cancer related) until December 31, 2011. A total of
      2103 participants without known cardiovascular disease and cancer at baseline
      were included in this prospective cohort study. Metabolic obesity was defined as
      having 2 or more of the following: high glucose, blood pressure, triglyceride, C
      reactive protein, and insulin resistance values and low high-density lipoprotein
      cholesterol levels; metabolic healthy status was defined as having 0 or 1 of
      these metabolic derangements. RESULTS: During median follow-up of 18.6 years,
      there were 344 and 296 deaths in the MONW and metabolically healthy normal-weight
      (MHNW) phenotypes, respectively. In MONW individuals, a 1-SD increment in
      adherence to a DASH diet (2 points) or HEI (14 points) was significantly
      associated with reductions (17% [hazard ratio (HR), 0.83; 95% CI, 0.72-0.97] and
      22% [HR, 0.78; 95% CI, 0.68-0.90], respectively) in the risk of all-cause
      mortality, after adjustment for potential confounders. The corresponding HRs for
      cardiovascular disease mortality were 0.72 (95% CI, 0.55-0.94) and 0.79 (95% CI,
      0.65-0.97), respectively. In addition, reduction of cancer mortality was observed
      with 1-SD increment of HEI (HR, 0.63; 95% CI, 0.46-0.88). However, no association
      was observed in the MHNW phenotype. Sensitivity analyses suggested relationships
      robust to different definitions of MONW and also dose responses with the number
      of metabolic derangements. CONCLUSION: Higher diet quality scores were associated
      with lower risk of mortality in normal-weight individuals with metabolic
      abnormalities.

PMID- 27712637
TI  - Survival, Risk Factors, and Effect of Treatment in 101 Patients With
      Calciphylaxis.
AB  - OBJECTIVE: To report on the survival and the associations of treatments upon
      survival of patients with calciphylaxis seen at a single center. PATIENTS AND
      METHODS: Using the International Classification of Diseases, Ninth Revision
      diagnosis code of 275.49 and the keyword "calciphylaxis" in the dismissal
      narrative, we retrospectively identified 101 patients with calciphylaxis seen at
      our institution between January 1, 1999, through September 20, 2014, using a
      predefined, consensus-developed classification scheme. RESULTS: The average age
      of patients was 60 years: 81 (80.2%) were women; 68 (68.0%) were obese; 19
      (18.8%) had stage 0 to 2 chronic kidney disease (CKD), 19 (18.9%) had stage 3 or
      4 CKD; 63 (62.4%) had stage 5 or 5D (dialysis) CKD. Seventy-five patients died
      during follow-up. Six-month survival was 57%. Lack of surgical debridement was
      associated with insignificantly lower 6-month survival (hazard ratio [HR]=1.99;
      95% CI, 0.96-4.15; P=.07) and significantly poorer survival for the entire
      duration of follow-up (HR=1.98; 95% CI, 1.15-3.41; P=.01), which was most
      pronounced in stage 5 or 5D CKD (HR=1.91; 95% CI, 1.03-3.56; P=.04). Among
      patients with stage 5/5D CKD, subtotal parathyroidectomy (performed only in
      patients with hyperparathyroidism) was associated with better 6-month (HR=0.12;
      95% CI, 0.02-0.90; P=.04) and overall survival (HR= 0.37; 95% CI, 0.15-0.87;
      P=.02). CONCLUSION: Calciphylaxis is associated with a high mortality rate.
      Significantly effective treatments included surgical debridement and subtotal
      parathyroidectomy in patients with stage 5/5D CKD with hyperparathyroidism.
      Treatments with tissue-plasminogen activator, sodium thiosulfate, and hyperbaric
      oxygen therapy were not associated with higher mortality.

PMID- 27712635
TI  - A Predictive Model of Mortality in Patients With Bloodstream Infections due to
      Carbapenemase-Producing Enterobacteriaceae.
AB  - OBJECTIVE: To develop a score to predict mortality in patients with bloodstream
      infections (BSIs) due to carbapenemase-producing Enterobacteriaceae (CPE).
      PATIENTS AND METHODS: A multinational retrospective cohort study (INCREMENT
      project) was performed from January 1, 2004, through December 31, 2013. Patients
      with clinically relevant monomicrobial BSIs due to CPE were included and randomly
      assigned to either a derivation cohort (DC) or a validation cohort (VC). The
      variables were assessed on the day the susceptibility results were available, and
      the predictive score was developed using hierarchical logistic regression. The
      main outcome variable was 14-day all-cause mortality. The predictive ability of
      the model and scores were measured by calculating the area under the receiver
      operating characteristic curve. The sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy were calculated for different
      cutoffs of the score. RESULTS: The DC and VC included 314 and 154 patients,
      respectively. The final logistic regression model of the DC included the
      following variables: severe sepsis or shock at presentation (5 points); Pitt
      score of 6 or more (4 points); Charlson comorbidity index of 2 or more (3
      points); source of BSI other than urinary or biliary tract (3 points);
      inappropriate empirical therapy and inappropriate early targeted therapy (2
      points). The score exhibited an area under the receiver operating characteristic
      curve of 0.80 (95% CI, 0.74-0.85) in the DC and 0.80 (95% CI, 0.73-0.88) in the
      VC. The results for 30-day all-cause mortality were similar. CONCLUSION: A
      validated score predictive of early mortality in patients with BSIs due to CPE
      was developed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01 764490.

PMID- 27712638
TI  - Calciphylaxis: A Disease of Pannicular Thrombosis.
AB  - OBJECTIVE: To identify coagulation risk factors in patients with calciphylaxis
      and the relationship between anticoagulation use and overall survival. PATIENTS
      AND METHODS: Study subjects were 101 patients with calciphylaxis seen at Mayo
      Clinic from 1999 to September 2014. Data including thrombophilia profiles were
      extracted from the medical records of each patient. Survival status was
      determined using patient registration data and the Social Security Death Index.
      Survival was estimated using the Kaplan-Meier method, and associations were
      evaluated using Cox proportional hazards models. RESULTS: Sixty-four of the 101
      patients underwent thrombophilia testing. Of these, a complete test panel was
      performed in 55 and a partial panel in 9. Severe thrombophilias observed in 60%
      (33 of 55) of the patients included antiphospholipid antibody syndrome protein C,
      protein S, or antithrombin deficiencies or combined thrombophilias. Of the 55
      patients, severe thrombophilia (85%, 23 of 27) was noted in patients who were not
      on warfarin at the time of testing (27). Nonsevere thrombophilias included
      heterozygous factor V Leiden (n=2) and plasminogen deficiency (n=1). For the
      comparison of survival, patients were divided into 3 treatment categories:
      Warfarin (n=63), other anticoagulants (n=20), and no anticoagulants (n=18). There
      was no statistically significant survival difference between treatment groups.
      CONCLUSION: Laboratory testing reveals a strikingly high prevalence of severe
      thrombophilias in patients with calciphylaxis, underscoring the importance of
      congenital and acquired thrombotic propensity potentially contributing to the
      pathogenesis of this disease. These findings may have therapeutic implications;
      however, to date, survival differences did not vary by therapeutic choice.

PMID- 27712639
TI  - Antithrombotic Approaches in Acute Coronary Syndromes: Optimizing Benefit vs
      Bleeding Risks.
AB  - It is estimated that in the United States, each year, approximately 620,000
      persons will experience an acute coronary syndrome and approximately 70% of these
      will have non-ST-elevation acute coronary syndrome. Cardiovascular disease still
      accounts for 1 of every 3 deaths in the United States, and there is an urgent
      need to improve the prognosis of patients presenting with acute coronary
      syndrome. Cardiovascular mortality and ischemic complications are common after
      acute coronary syndrome, and the advent of newer antithrombotic therapies has
      reduced ischemic complications, but at the expense of greater bleeding. The new
      antithrombotic agents also raise the challenge of choosing between multiple
      potential therapeutic combinations to minimize recurrent ischemia without a
      concomitant increase in bleeding, a decision that often varies according to an
      individual patient's relative propensity for ischemia versus hemorrhage. In this
      review, we will synthesize the available information to arm health care providers
      with the contemporary knowledge on antithrombotic therapy and individualize
      treatment decisions.

PMID- 27712640
TI  - Importance of Rapid Eye Movement Sleep Behavior Disorder to the Primary Care
      Physician.
AB  - Sleep disorders and neurodegenerative diseases are commonly encountered in
      primary care. A common, but underdiagnosed sleep disorder, rapid eye movement
      sleep behavior disorder (RBD), is highly associated with Parkinson disease and
      related disorders. Rapid eye movement sleep behavior disorder is common. It is
      estimated to affect 0.5% of the general population and more than 7% of
      individuals older than 60 years; however, most cases go unrecognized. Rapid eye
      movement sleep behavior disorder presents as dream enactment, often with patients
      thrashing, punching, and kicking while they are sleeping. Physicians can quickly
      assess for the presence of RBD with high sensitivity and specificity by asking
      patients the question "Have you ever been told that you act out your dreams, for
      example by punching or flailing your arms in the air or screaming and shouting in
      your sleep?" Patients with RBD exhibit subtle signs of neurodegenerative disease,
      such as mild motor slowing, constipation, or changes in sense of smell. These
      signs and symptoms may predict development of a neurodegenerative disease within
      3 years. Ultimately, most patients with RBD develop a neurodegenerative disease,
      highlighting the importance of serial neurological examinations to assess for the
      presence of parkinsonism and/or cognitive impairment and prognostic counseling
      for these patients. Rapid eye movement sleep behavior disorder is treatable with
      melatonin (3-6 mg before bed) or clonazepam (0.5-1 mg before bed) and may be the
      most common, reversible cause of sleep-related injury. Thus, it is important to
      identify patients at risk of RBD in a primary care setting so that bedroom safety
      can be addressed and treatment may be initiated.

PMID- 27712642
TI  - "Petrified Ears": Auricular Ossification in Adrenal Insufficiency.

PMID- 27712643
TI  - Sacral Chordoma.

PMID- 27712644
TI  - Mayo Ancestors by Glenna Goodacre, Victoria Davila, and Daniel Anthony.
AB  - Recognizing the contribution art has had in the Mayo Clinic environment since the
      original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings
      features some of the numerous works of art displayed throughout the buildings and
      grounds on Mayo Clinic campuses as researched and interpreted by the author.

PMID- 27712641
TI  - Anorectal and Pelvic Pain.
AB  - Although pelvic pain is a symptom of several structural anorectal and pelvic
      disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease),
      this comprehensive review will focus on the 3 most common nonstructural, or
      functional, disorders associated with pelvic pain: functional anorectal pain (ie,
      levator ani syndrome, unspecified anorectal pain, and proctalgia fugax),
      interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic
      pelvic pain syndrome. The first 2 conditions occur in both sexes, while the
      latter occurs only in men. They are defined by symptoms, supplemented with
      levator tenderness (levator ani syndrome) and bladder mucosal inflammation
      (interstitial cystitis). Although distinct, these conditions share several
      similarities, including associations with dysfunctional voiding or defecation,
      comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and
      increased health care utilization. Several factors, including pelvic floor muscle
      tension, peripheral inflammation, peripheral and central sensitization, and
      psychosocial factors, have been implicated in the pathogenesis. The management is
      tailored to symptoms, is partly supported by clinical trials, and includes
      multidisciplinary approaches such as lifestyle modifications and pharmacological,
      behavioral, and physical therapy. Opioids should be avoided, and surgical
      treatment has a limited role, primarily in refractory interstitial cystitis.

PMID- 27712645
TI  - Foreword: Child Health Disparities.

PMID- 27712646
TI  - Child Health Disparities in the 21st Century.
AB  - The topic of persistent child health disparities remains a priority for
      policymakers and a concern for pediatric clinicians. Health disparities are
      defined as differences in adverse health outcomes for specific health indicators
      that exist across sub-groups of the population, frequently between minority and
      majority populations. This review will highlight the gains that have been made
      since the 1990s as well as describe disparities that have persisted or have
      worsened into the 21st century. It will also examine the most potent social
      determinants and their impact on the major disparities in mortality, preventive
      care, chronic disease, mental health, educational outcomes, and exposure to
      selected environmental toxins. Each section concludes with a description of
      interventions and innovations that have been successful in reducing child health
      disparities.

PMID- 27712647
TI  - Commentary: Health Disparities, Social Justice and the Practice of Pediatrics.

PMID- 27712648
TI  - Impact of Lipoprotein(a) on Long-term Outcomes in Patients With Diabetes Mellitus
      Who Underwent Percutaneous Coronary Intervention.
AB  - Patients with diabetes mellitus (DM) are at twofold to fourfold higher
      cardiovascular risk than those without DM. Serum levels of lipoprotein(a) (Lp(a))
      can be risk factors for adverse events. However, the clinical implications of
      Lp(a) in patients with DM who underwent percutaneous coronary intervention (PCI)
      is unknown. The aim of the study was to determine the role of Lp(a) in patients
      with DM who underwent PCI. A total of 3,508 patients were treated by PCI from
      1997 to 2011 at our institution. Among them, we analyzed consecutive 1,546
      patients with DM. Eligible 1,136 patients were divided into 2 groups (high Lp(a)
      [n = 575] and low Lp(a) [n = 561]) by the median of Lp(a) levels. The number of
      chronic kidney disease, multivessel disease, and the level of LDL-C were higher
      in the group with high Lp(a) than with low Lp(a). The median follow-up period was
      4.7 years. Event rate of all-cause death was same between the 2 groups (p =
      0.37). However, cumulative incidence of cardiac death and acute coronary syndrome
      was significantly higher in the high Lp(a) than in the low Lp(a) group (p =
      0.03). Multivariable analysis selected a high Lp(a) level as an independent
      predictor of cardiac death and acute coronary syndrome (hazard ratio 1.20; 95%
      confidence interval 1.00 to 1.42; p = 0.04). In conclusion, a high Lp(a) value
      could be associated with advanced cardiac events after PCI for patients with DM.

PMID- 27712650
TI  - Effects of NMDA and non-NMDA ionotropic glutamate receptors in the medial
      preoptic area on body temperature in awake rats.
AB  - Glutamate when microinjected at the medial preoptic area (mPOA) influences brain
      temperature (Tbr) and body temperature (Tb) in rats. Glutamate and its various
      receptors are present at the mPOA. The aim of this study was to identify the
      contribution of each of the ionotropic glutamatergic receptors at the mPOA on
      changes in Tbr and Tb in freely moving rats. Adult male Wistar rats (n=40) were
      implanted with bilateral guide cannula with indwelling styli above the mPOA. A
      telemetric transmitter was implanted at the peritoneum to record Tb and locomotor
      activity (LMA). A precalibrated thermocouple wire implanted near the hypothalamus
      was used to assess Tbr. Specific agonist for each ionotropic glutamate receptor
      was microinjected into the mPOA and its effects on temperature and LMA were
      measured in the rats. The rats were also microinjected with the respective
      ionotropic receptor antagonists, 15min prior to the microinjection of each
      agonist. Amongst amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N
      methyl-d-aspartate (NMDA) and kainic acid, AMPA increased Tb and LMA when
      injected at the mPOA. Specific antagonists for AMPA receptors was able to
      attenuate this increase (p<0.005). Pharmacological blockade of NMDA was able to
      lower Tbr only. Microinjection of kainic acid and its antagonist had no effect on
      the variables. The finding of the study suggests that activation of the AMPA
      receptors at the mPOA, leads to the rise in body temperature.

PMID- 27712651
TI  - Cooler performance breadth in a viviparous skink relative to its oviparous
      congener.
AB  - Susceptibility of species to climate change varies depending on many biological
      and environmental traits, such as reproductive mode and climatic exposure. For
      example, wider thermal tolerance breadths are associated with more climatically
      variable habitats and viviparity could be associated with greater vulnerability
      relative to oviparity. However, few examples exist detailing how such
      physiological and environmental traits together might shape species thermal
      performance. In this study we compared the thermal tolerance and performance of
      two sympatric skink congeners in Hong Kong that differ in habitat use and
      reproductive mode. The viviparous Sphenomorphus indicus lives on the forest floor
      while the oviparous Sphenomorphus incognitus occupies stream edges. We quantified
      the thermal environments in each of these habitats to compare climatic exposure
      and then calculated thermal safety margins, potential daily activity times within
      each species' thermal optimal range, and possible climate change vulnerability.
      Although we did not detect any differences in thermal tolerance range or thermal
      environments across habitats, we found cooler performance in S. indicus relative
      to S. incognitus. Moreover, while optimal activity time increases for both skinks
      under a warming scenario, we project that the thermal safety margin of S. indicus
      would narrow to nearly zero, thus losing its buffering capacity to potential
      extreme climate events in the future. This research is thus consistent with
      recent studies emphasizing the vulnerability of viviparous reptiles to a warming
      climate. The results together furthermore highlight the complexity in how
      environmental and physiological traits at multiple spatial scales structure
      climate change vulnerability of ectothermic species.

PMID- 27712649
TI  - High-Sensitivity C-Reactive Protein and Risk of Stroke in Atrial Fibrillation
      (from the Reasons for Geographic and Racial Differences in Stroke Study).
AB  - The relation between inflammation and prothrombotic state in atrial fibrillation
      (AF) is well recognized. This suggests a potential role for high-sensitivity C
      reactive protein (hs-CRP), a marker of systemic inflammation, in improving
      prediction of stroke in participants with AF. Cox proportional hazard analysis
      was used to examine the risk of stroke in 25,841 participants (40% black and 55%
      women) with and without AF who were enrolled in the Reasons for Geographic and
      Racial Differences in Stroke study from 2003 to 2007. Baseline AF (n = 2,132) was
      ascertained by electrocardiogram and self-reported history of previous physician
      diagnosis. Stroke events were identified and adjudicated during 8.3 years of
      follow-up. A total of 655 incident strokes occurred during follow-up. In a model
      adjusted for sociodemographics, traditional stroke risk factors, and use of
      aspirin and warfarin, higher levels of hs-CRP were associated with increased
      overall stroke risk (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.10 to
      1.54, and HR 1.06, 95% CI 1.01 to 1.12 for hs-CRP >3 mg/L and per 1-SD increase,
      respectively). Higher levels of hs-CRP continued to be associated with incident
      stroke in participants without AF (HR 1.31, 95% CI 1.09 to 1.57, and HR 1.06, 95%
      CI 1.01 to 1.12 for hs-CRP >3 mg/L and per 1-SD increase, respectively) but not
      in those with AF (HR 1.22, 95% CI 0.78 to 1.91, and HR 1.01, 95% CI 0.82 to 1.23
      for hs-CRP >3 mg/L and per 1-SD increase, respectively). In conclusion, although
      hs-CRP was significantly associated with stroke risk in this population, it seems
      to be limited to those without AF. These findings suggest a limited value of hs
      CRP in improving stroke risk stratification in subjects with AF.

PMID- 27712652
TI  - Life-history responses of the rice stem borer Chilo suppressalis to temperature
      change: Breaking the temperature-size rule.
AB  - Temperature is a key environmental factor for ectotherms and affects a large
      number of life history traits. In the present study, development time from
      hatching to pupation and adult eclosion, pupal and adult weights of the rice stem
      borer, Chilo suppressalis were examined at 22, 25, 28 and 31 degrees C under
      L18:D 6. Larval and pupal times were significantly decreased with increasing
      rearing temperature and growth rate was positively correlated with temperature.
      Larval and pupal developmental times were not significantly different between
      females and males. The relationship between body weight and rearing temperature
      in C. suppressalis did not follow the temperature-size rule (TSR), both males and
      females gained the highest body weight at 31 degrees C. Females were
      significantly larger than males at all temperatures, showing a female biased sex
      size dimorphism (SSD). Contrary to Rensch's rule, SSD and body weight in C.
      suppressalis tended to increase with rising temperature. Male pupae lost
      significantly more weight at metamorphosis compared to females. We discuss the
      adaptive significance of the reverse-TSR in the moth's life history.

PMID- 27712653
TI  - The influence of cooling and TRPM8 ion channel activation on the level of pro
      inflammatory cytokines in normotensive and hypertensive rats.
AB  - The role of thermosensitive TRP ion channels in physiological processes in the
      whole organism is far from being clear. In present work we tried to understand
      the possible participation of the cold-sensitive ion channel TRPM8 in regulation
      of the pro-inflammatory cytokine level in blood, and to see if hypertension
      (widely spread disease) changes this relationship. Experiments were carried out
      on normotensive Wistar rats and rats with inherited stress-induced arterial
      hypertension. The effects of deep rapid and slow cooling with decrease in rectal
      temperature by 3 degrees C, and activation of the skin TRPM8 ion channel by its
      agonist menthol (application of 1% L-menthol) on the concentration of pro
      inflammatory cytokines (IL-6, IL-1beta and TNFalpha) in blood have been studied.
      The data have shown that the TRPM8 ion channel participates in regulation of pro
      inflammatory cytokine in the whole organism, as well as exposure to cold. In
      normotensive animals the activation of the cold-sensitive TRPM8 ion channel in
      skin by its agonist menthol without any temperature shifts causes an increase
      (about two fold) of pro-inflammatory cytokines IL-6 and IL-1 beta in blood
      without any changes in the level of TNFalpha. The effect of cooling (slow or
      rapid) on IL-6 and IL-1beta is comparable with the effect of the TRPM8
      activation. The changes in TNFalpha concentration were observed only at slow
      cooling. In hypertensive rats there were no changes in the level of pro
      inflammatory cytokines under the effect of cooling or activation of the TRPM8 ion
      channel. This evidences for the decrease in TRPM8 activity under arterial
      hypertension. One of possible mechanisms of profound changes at arterial
      hypertension may be the alteration in activity of some ion channels, and TRPM8 is
      one of them.

PMID- 27712654
TI  - Thermal and substrate color-induced melanization in laboratory reared red-eared
      sliders (Trachemys scripta elegans).
AB  - Color and pigmentation patterns of the integument can facilitate crypsis,
      thermoregulation, and social signaling. According to the "thermal melanism
      hypothesis", cold environmental temperature should increase the quantity of
      melanin that is deposited in the integument thereby facilitating radiative
      warming. We studied the influences of water temperature (26 degrees C or 31
      degrees C) and substrate color (black or white) on the degree of melanization in
      the red-eared slider, Trachemys scripta elegans, under laboratory conditions.
      Turtles reared on a black substrate, or in 26 degrees C water, for 120 days were
      darker than those reared on a white substrate or in 31 degrees C water. A
      potential tradeoff between the fitness benefits of crypsis and the benefits of
      radiative warming through melanism was detected because turtles reared in 26
      degrees C water and on a white substrate were darker than those reared on a white
      substrate and in 31 degrees C water. Low temperatures limited metabolic processes
      because turtles reared in 26 degrees C water grew more slowly than those reared
      in 31 degrees C water. However, histological analyses revealed that melanization
      was a dynamic process in all treatments confirming that the degree of
      melanization in the cool water treatment was not influenced by the initial and
      relatively dark hatchling coloration in individuals that grew relatively slowly.

PMID- 27712655
TI  - Comparison of abdominal skin temperature between fertile and infertile women by
      infrared thermography: A diagnostic approach.
AB  - This retrospective study aimed to evaluate the differences in abdominal
      temperature (AT) between fertile (n=206; age) and infertile (n=250) women between
      the ages of 30 and 39 years. We evaluated the differences in two distinctive skin
      temperatures by thermography: DeltaT1 (CV8 index) - difference in temperature
      between the mid-abdomen (CV8 acupuncture area) and ventral upper arm (VUA) and
      DeltaT2 (CV4 index) - difference in temperature between the lower abdomen (CV4
      acupuncture area) and VUA. The results indicated that the DeltaT1 and DeltaT2 of
      infertile women were significantly lower (by 1.05 degrees C and 0.79 degrees C,
      respectively; p<0.001, both) compared to those of fertile women. Additionally,
      the area under the curve of DeltaT1 (0.78) was greater compared to that of
      DeltaT2 (0.736), and its threshold was set at 0.675 degrees C, by which, the
      sensitivity and specificity of DeltaT1 for determination of fertility were found
      to be 80.8% and 68.4%, respectively. In conclusion, infertility is associated
      with lower AT. The decrease in AT in infertile women might be due to poor blood
      perfusion to the core muscles and tissues of the body. These findings provide a
      basis for further research for evaluation of clinical feasibility of thermography
      for analysis of infertility in women. Further evaluation of the influence of AT
      on fertility outcomes is required to determine the causal relationship between AT
      and infertility.

PMID- 27712656
TI  - Numerical investigation of thermal response of laser-irradiated biological tissue
      phantoms embedded with gold nanoshells.
AB  - The work presented in this paper focuses on numerically investigating the thermal
      response of gold nanoshells-embedded biological tissue phantoms with potential
      applications into photo-thermal therapy wherein the interest is in destroying the
      cancerous cells with minimum damage to the surrounding healthy cells. The tissue
      phantom has been irradiated with a pico-second laser. Radiative transfer equation
      (RTE) has been employed to model the light-tissue interaction using discrete
      ordinate method (DOM). For determining the temperature distribution inside the
      tissue phantom, the RTE has been solved in combination with a generalized non
      Fourier heat conduction model namely the dual phase lag bio-heat transfer model.
      The numerical code comprising the coupled RTE-bio-heat transfer equation,
      developed as a part of the current work, has been benchmarked against the
      experimental as well as the numerical results available in the literature. It has
      been demonstrated that the temperature of the optical inhomogeneity inside the
      biological tissue phantom embedded with gold nanoshells is relatively higher than
      that of the baseline case (no nanoshells) for the same laser power and operation
      time. The study clearly underlines the impact of nanoshell concentration and its
      size on the thermal response of the biological tissue sample. The comparative
      study concerned with the size and concentration of nanoshells showed that 60nm
      nanoshells with concentration of 5*1015mm-3 result into the temperature levels
      that are optimum for the irreversible destruction of cancer infected cells in the
      context of photo-thermal therapy. To the best of the knowledge of the authors,
      the present study is one of the first attempts to quantify the influence of gold
      nanoshells on the temperature distributions inside the biological tissue phantoms
      upon laser irradiation using the dual phase lag heat conduction model.

PMID- 27712657
TI  - Effects of rapid temperature fluctuations prior to breeding on reproductive
      efficiency in replacement gilts.
AB  - Rapidly cooling pigs after heat stress (HS) results in a pathophysiological
      condition, and because rapid temperature fluctuations may be associated with
      reduced reproductive success in sows, it lends itself to the hypothesis that
      these conditions may be linked. Objectives were to determine the effects of rapid
      cooling on thermal response and future reproductive success in pigs. Thirty-six
      replacement gilts (137.8+/-0.9kg BW) were estrus synchronized and then 14.1+/-0.4
      d after estrus confirmation, pigs were exposed to thermoneutral conditions (TN;
      n=12; 19.7+/-0.9 degrees C) for 6h, or HS (36.3+/-0.5 degrees C) for 3h, followed
      by 3h of rapid cooling (HSRC; n=12; immediate TN exposure and water dousing) or
      gradual cooling (HSGC; n=12; gradual decrease to TN conditions) repeated over 2
      d. Vaginal (TV) and gastrointestinal tract temperatures (TGI) were obtained every
      15min, and blood was collected on d 1 and d 2 during the HS and recovery periods
      at 180 and 60min, respectively. Pigs were bred 8.3+/-0.8 d after thermal
      treatments over 2 d. Reproductive tracts were collected and total fetus number
      and viability were recorded 28.0+/-0.8 d after insemination. HS increased TV and
      TGI (P=0.01; 0.98 degrees C) in HSRC and HSGC compared to TN pigs. During
      recovery, TV was reduced from 15 to 105min (P=0.01; 0.33 degrees C) in HSRC
      compared to HSGC pigs, but no overall differences in TGI were detected (P<0.05;
      39.67 degrees C). Rapid cooling increased (P<0.05) TNFalpha compared to HSGC and
      TN pigs during recovery-d 1 (55.2%), HS-d 2 (35.1%), and recovery-d 2 (64.9%).
      Viable fetuses tended to be reduced (P=0.08; 10.5%) and moribund fetuses tended
      to be increased (P=0.09; 159.3%) in HSRC compared to HSGC and TN pigs. In
      summary, rapid cooling prior to breeding may contribute to reduced fetal
      viability and reproductive success in pigs.

PMID- 27712658
TI  - Effect of thermal stress on fertility and egg quality of Japanese quail.
AB  - Heat stress is one of the major causes of a decreased performance of laying quail
      in tropical and subtropical countries. The aim of this study was to investigate
      the impact of temperature humidity index (THI) on fertility aspects, external and
      internal egg quality parameters in Japanese quail. One hundred and forty four
      (144) Japanese quail, 12 of weeks age, were used. Birds were divided randomly
      into three equal groups, control (at low THI, lower than 70), H1 (at moderate
      THI, 70-75) and H2 (at high THI, 76-80). Quail in the control and H1 groups had
      significant greater fertility (p=0.021) and hatchability % (p=0.037), compared
      with H2 group. Quail in the control group (at low THI) laid heavier egg weight
      with a higher external (egg weight (p=0.03), shell thickness, shell weight,
      eggshell ratio and eggshell density (p=0.001)) and internal egg quality score
      (albumin weight (p=0.026), yolk height (p=0.003), yolk index (p=0.039) and Haugh
      unit (p=0.001)). Otherwise, such quality traits were compromised in heat-stressed
      quail. At the high THI level, egg weight had a significant positive correlation
      with albumin weight (r=0.58, p<0.01), yolk weight (r=0.22, p<0.05), albumen ratio
      (r=0.17, p<0.05), yolk height (r=0.14, p<0.05) and yolk index (r=0.18, p<0.05),
      but was negatively correlated with yolk ratio (r=-0.15, p<0.05). Japanese quail
      exposed to heat stress (THI over 75) revealed drop in fertility indices and egg
      quality traits, indicating a detrimental policy of economic income.

PMID- 27712659
TI  - Sexual differences in behavioral thermoregulation of the lizard Scelarcis
      perspicillata.
AB  - Temperature determines all aspects of the biology of ectotherms. Although sexual
      differences in thermal ecology are not the rule in lizards, some species exhibit
      such differences. We studied the effect of sex and reproductive condition on the
      thermoregulation of an introduced population of Scelarcis perspicillata during
      the summer in Menorca (Balearic Islands, Spain). These lizards live in the wall
      surfaces of a limestone quarry, where the sun is scarce because of the narrowness
      of the quarry walls. The population is sexually dimorphic, with larger males than
      females. We measured body temperature (Tb) of adult males and females in the
      field, and air (Ta) and substrate temperature (Ts) at the capture sites, and
      recorded exposure to sunlight, height of the perch, and type of substrate. We
      also recorded operative temperatures (Te) as a null hypothesis of
      thermoregulation. Finally, we studied the thermal preferences of adult males and
      females in a laboratory thermal gradient. Thermal preferences were similar for
      pregnant and non-pregnant females, and sex did not affect the thermal preferences
      of lizards, even after controlling for the effect of body size. However, in the
      field, females achieved higher Tb than males, and occupied microhabitats with
      higher Ta and Ts and lower perch heights than males. Furthermore, females
      selected perches in full sun at a higher frequency than males. As a consequence,
      females achieved a higher accuracy and effectiveness of thermoregulation (0.89)
      than males (0.84). Thus, all else being equal, females would achieve a higher
      performance than males. The observed results are attributable to sexual
      differences in behaviour, probably in relation with the reproductive season.

PMID- 27712660
TI  - Effect of cyclical cold stress during embryonic development on aspects of
      physiological responses and HSP70 gene expression of chicks.
AB  - The objective of the present study was to evaluate the effects of cyclical lower
      incubation temperature at different embryonic ages on the hatchability, body and
      organs weights, thyroid hormones, and liver HSP70 gene expression of newly
      hatched chicks. In a completely randomized design, fertile eggs of a broiler
      breeder (34 weeks of age) were assigned to three treatment groups with six
      replicates and 145 eggs per each. The treatment groups were as: control group (C)
      that eggs were incubated at 37.6 degrees C during the whole incubation period;
      incubation temperature was decreased to 36 degrees C for 3h per day at embryonic
      age from 12 to 14 (T1); and incubation temperature was decreased to 36 degrees C
      for 3h per day at embryonic age from 15 to 17 (T2). No significant difference was
      found among treatments for hatchability (P>0.05). There were no differences
      (P>0.05) among treatments for body weight and liver weight, while heart weight of
      chicks in T1 and T2 groups were significantly higher than the control group
      (P<0.05). There were no differences (P>0.05) among treatments for the levels of
      thyroid hormones, however, the levels of both hormones tended to increase in
      chicks exposed to cold stress (T1 and T2). Chicks in T2 group had higher liver
      HSP70 gene expression compared with those in T1 and the control group (P<0.05).
      Cold stress in both incubation periods had no significant effect on the plasma
      levels of aspartate aminotransferase and alanine aminotransferase. Treatments had
      no effect on the plasma levels of glucose, cholesterol and triglyceride. The
      results of this study suggest that cyclical lower incubation temperatures (36
      degrees C) at the embryonic age from day 15-17 could induce the liver HSP70 gene
      expression, without negative effects on the hatchability and body weight of
      hatched chicks.

PMID- 27712661
TI  - The particularities of a remote islet shape the thermoregulatory profile of an
      endemic Mediterranean lizard.
AB  - Environmental temperatures considerably affect the reptilian ability for
      thermoregulation and harsh climatic conditions may impose a highly effective body
      temperature regulation to lizards. Such demanding conditions are more common to
      extreme mainland habitats (e.g. deserts or mountains). To the contrary, islands
      have more benign climate conditions thanks to the thermal buffering effect of the
      surrounding sea. However, this favorable effect may be eliminated in small size
      islets where the scarcity of thermal shelters and exposure to high winds create
      challenging conditions. Here we investigate the impact of a tough islet habitat
      on the thermoregulation of Podarcis levendis, a lacertid lizard endemic to two
      rocky islets in the north Cretan Sea, Greece. To evaluate the thermoregulatory
      effectiveness of P. levendis we measured operative and body temperatures in the
      field and the preferred body temperatures in the lab. Analyses of the thermal
      data revealed an accurate, precise, and effective thermoregulator, achieving very
      high thermoregulation values (E =0.91, de--db- =7.6). This high effectiveness
      comes to compensate living in an inhospitable habitat as the operative
      temperatures denote (de =7.79). Our findings, together with the limited published
      literature, suggested the lack of a general pattern for all insular lizards and
      indicated a possible deviation for islet habitats.

PMID- 27712662
TI  - Effect of stride frequency on thermoregulatory responses during endurance running
      in distance runners.
AB  - Changing stride frequency may influence oxygen uptake and heart rate during
      running as a function of running economy and central command. This study
      investigated the influence of stride frequency manipulation on thermoregulatory
      responses during endurance running. Seven healthy endurance runners ran on a
      treadmill at a velocity of 15km/h for 60min in a controlled environmental chamber
      (ambient temperature 27 degrees C and relative humidity 50%), and stride
      frequency was manipulated. Stride frequency was intermittently manipulated by
      increasing and decreasing frequency by 10% from the pre-determined preferred
      frequency. These periods of increase or decrease were separated by free frequency
      running in the order of free stride frequency, stride frequency manipulation
      (increase or decrease), free stride frequency, and stride frequency manipulation
      (increase or decrease) for 15min each. The increased and decreased stride
      frequencies were 110% and 91% of the free running frequency, respectively (196+/
      6, 162+/-5, and 178+/-5steps/min, respectively, P<0.01). Compared to the control,
      stride frequency manipulation did not affect rectal temperature, heart rate, or
      the rate of perceived exhaustion during running. Whole-body sweat loss increased
      significantly when stride frequency was manipulated (1.48+/-0.11 and 1.57+/
      0.11kg for control and manipulated stride frequencies, respectively, P<0.05), but
      stride frequency had a small effect on sweat loss overall (Cohen's d=0.31). A
      higher mean skin temperature was also observed under mixed frequency conditions
      compared to that in the control (P<0.05). While the precise mechanisms underlying
      these changes remain unknown (e.g. running economy or central command), our
      results suggest that manipulation of stride frequency does not have a large
      effect on sweat loss or other physiological variables, but does increase mean
      skin temperature during endurance running.

PMID- 27712663
TI  - Whole- and partial-body cryostimulation/cryotherapy: Current technologies and
      practical applications.
AB  - Cold therapy is commonly used as a method to relieve pain and inflammation. This
      review focuses primarily on two methods of cold therapy that have received recent
      attention: whole-body cryotherapy and partial-body cryotherapy. These methods are
      used to induce physiological and psychological benefits in humans in the context
      of medicine, health and sports. The subjects experiencing cryotherapy are dressed
      in minimal clothing and are exposed to very cold air (at -110 degrees C or less)
      for 1-4min. Despite the increasing scientific interest in these methods, there is
      a lack of information about the technologies used. Moreover, there is no existing
      reference concerning exposure protocols and the relationship between temperature,
      duration, number of repetitions and the treatments' desired effects. The aim of
      this review is to compare whole- and partial-body cryotherapy effects (especially
      on skin temperature) and to classify the protocols for exposure according to the
      desired effects. This review emphasises 1) the lack of information concerning the
      actual temperatures inside the cabin or chamber during exposure and 2) the
      heterogeneity among the exposure protocols that have been reported in the
      scientific literature. This review will be valuable and relevant to health
      professionals endeavouring to optimize the cold treatments offered to patients
      and producers of cryotherapy apparatus striving to create more efficient devices
      that meet market requirements.

PMID- 27712664
TI  - Evaluation of physiological strain in hot work areas using thermal imagery.
AB  - BACKGROUND: Monitoring core body temperature to identify heat strain in workers
      engaged in hot work in heat stress environments is intrusive and expensive.
      Nonintrusive, inexpensive methods are needed to calculate individual
      Physiological Strain Index (PSI). OBJECTIVE: Thermal imaging and heart rate
      monitoring were used in this study to calculate Physiological Strain Index (PSI)
      from thermal imaging temperatures of human subjects wearing thermal protective
      garments during recovery from hot work. METHODS: Ten male subjects were evaluated
      for physiological strain while participating in hot work. Thermal images of the
      head and neck were captured with a high-resolution thermal imaging camera
      concomitant with measures of gastrointestinal and skin temperature. Lin's
      concordance correlation coefficient (rho_c), Pearson's coefficient (r) and bias
      correction factor (C-b) were calculated to compare thermal imaging based
      temperatures to gastrointestinal temperatures. Calculations of PSI based thermal
      imaging recorded temperatures were compared to gastrointestinal based PSI.
      RESULTS: Participants reached a peak PSI of 5.2, indicating moderate heat strain.
      Sagittal measurements showed low correlation (rho_c=0.133), moderate precision
      (r=0.496) and low accuracy (C_b=0.269) with gastrointestinal temperature. Bland
      Altman plots of imaging measurements showed increasing agreement as
      gastrointestinal temperature rose; however, the Limits of Agreement (LoA) fell
      outside the +/-0.25C range of clinical significance. Bland-Altman plots of PSI
      calculated from imaging measurements showed increasing agreement as
      gastrointestinal temperature rose; however, the LoA fell outside the +/-0.5 range
      of clinical significance. CONCLUSION: Results of this study confirmed previous
      research showing thermal imagery is not highly correlated to body core
      temperature during recovery from moderate heat strain in mild ambient conditions.
      Measurements display a trend toward increasing correlation at higher body core
      temperatures. Accuracy was not sufficient at mild to moderate heat strain to
      allow calculation of individual physiological stress.

PMID- 27712665
TI  - Proteomic response of mouse pituitary gland under heat stress revealed active
      regulation of stress responsive proteins.
AB  - The mapping of tissue proteomes can identify the molecular regulators and
      effectors of their physiological activity. However, proteomic response of a
      mammalian tissue against heat stress (HS) particularly of the pituitary gland has
      not yet been resolved. The proteomic response of the mouse pituitary gland
      against HS at 40oC was evaluated by iTRAQ. We found that, HS actively regulates
      stress-related proteins. Among 375 differentially expressed proteins, 26 up and
      46 downregulated proteins were found as stress responsive proteins. Two proteins
      belonging to the HSP70 and one to HSP90 family were found upregulated. Meanwhile,
      the expression of HSP90alpha (Cytosolic), HSP60, and HSP84b were observed to be
      downregulated. A neuroprotective enzyme Nmnat3 was observed to be significantly
      upregulated. Three proteins related to the intermediate filament (IF) proteins
      (lamins, vimentin and keratins) were also found to be upregulated. We reported,
      an association between the IF proteins and HSPs as a biological marker of HS. The
      expression of Apo A-IV was upregulated and might be one explanation for low food
      intake during HS. Our findings indicated that, differentially expressed proteins
      might be played important roles in combating HS.

PMID- 27712666
TI  - Altitudinal variation in lifespan of Drosophila melanogaster populations from the
      Firtina Valley, northeastern Turkey.
AB  - Studies of altitudinal changes in phenotype and genotype can complement studies
      of latitudinal patterns and provide evidence of natural selection in response to
      climatic factors. In Drosophila melanogaster, latitudinal variation in phenotype
      and genotype has been well studied, but altitudinal patterns have rarely been
      investigated. We studied populations from six different altitudes varying between
      35m and 2173m in the Firtina Valley in northeastern part of Turkey to evaluate
      clinal trends in lifespan under experimental conditions. Lifespan in the D.
      melanogaster populations was examined in relation to altitude, sex, temperature
      (25 degrees C and 29 degrees C), and dietary yeast concentration (5g/L and
      25g/L). As expected high temperature decrease lifespan in all populations.
      However, it was shown that lifespan was slightly affected by dietary stress. We
      found that lifespan decreases significantly under thermal stress conditions with
      increasing altitude. Moreover, there was a slightly negative relationship between
      altitude and lifespan, which was closely associated with climatic factors such as
      temperature and precipitation, may suggest local adaptation to climate.

PMID- 27712667
TI  - Effects of environmental variables on surface temperature of breeding adult
      female northern elephant seals, Mirounga angustirostris, and pups.
AB  - Pinnipeds spend extended periods of time on shore during breeding, and some
      temperate species retreat to the water if exposed to high ambient temperatures.
      However, female northern elephant seals (Mirounga angustirostris) with pups
      generally avoid the water, presumably to minimize risks to pups or male
      harassment. Little is known about how ambient temperature affects
      thermoregulation of well insulated females while on shore. We used a
      thermographic camera to measure surface temperature (Ts) of 100 adult female
      elephant seals and their pups during the breeding season at Point Reyes National
      Seashore, yielding 782 thermograms. Environmental variables were measured by an
      onsite weather station. Environmental variables, especially solar radiation and
      ambient temperature, were the main determinants of mean and maximum Ts of both
      females and pups. An average of 16% of the visible surface of both females and
      pups was used as thermal windows to facilitate heat loss and, for pups, this area
      increased with solar radiation. Thermal window area of females increased with
      mean Ts until approximately 26 degrees C and then declined. The Ts of both age
      classes were warmer than ambient temperature and had a large thermal gradient
      with the environment (female mean 11.2+/-0.2 degrees C; pup mean 14.2+/-0.2
      degrees C). This large gradient suggests that circulatory adjustments to bypass
      blubber layers were sufficient to allow seals to dissipate heat under most
      environmental conditions. We observed the previously undescribed behavior of
      females and pups in the water and determined that solar radiation affected this
      behavior. This may have been possible due to the calm waters at the study site,
      which reduced the risk of neonates drowning. These results may predict important
      breeding habitat features for elephant seals as solar radiation and ambient
      temperatures change in response to changing climate.

PMID- 27712668
TI  - Keeping it in the family: the impact of marital status and next of kin on cancer
      treatment and survival.
AB  - BACKGROUND: This study examines the impact of marriage and next of kin identity
      on timing of diagnosis, treatment, and survival in cancer patients. METHODS:
      Retrospective review of patients with 5 solid tumor types treated at an academic
      medical center from 2002 to 2012. Exposures of interest were marriage status at
      time of diagnosis and familial relationship with next of kin (NOK). Association
      with overall survival determined via Cox regressions and with early diagnosis
      (stage I to II) and receipt of surgery via logistic regressions. RESULTS:
      Marriage was not associated with early diagnosis for any cancer type. After
      adjustment, being married was associated with significantly higher odds of
      receiving surgery only for pancreatic cancer and with improved survival for
      breast and lung cancers. Having a nuclear relationship with NOK was not
      associated with any outcomes. CONCLUSIONS: Marriage status was associated with
      improved outcomes for certain cancers whereas familial relationship with NOK was
      not.

PMID- 27712669
TI  - Intraoperative adverse events during irreversible electroporation-a call for
      caution.
AB  - BACKGROUND: Irreversible electroporation is increasingly used for treatment of
      solid tumors, but safety data remain scarce. This study aimed to describe
      intraoperative adverse events associated with irreversible electroporation in
      patients undergoing solid tumor ablation. METHODS: We analyzed demographic and
      intraoperative data for patients (n = 43) undergoing irreversible electroporation
      for hepato-pancreato-biliary and retroperitoneal malignancies (2012 to 2015).
      Adverse events were defined as cardiac, surgical, or equipment-related. RESULTS:
      Adverse events (n = 20, 47%) were primarily cardiac (90%, n = 18), including
      blood pressure elevation (77%, n = 14/18) and arrhythmia (16%, n = 7/43). All but
      one was managed medically, 1 patient with arrhythmia required termination of
      ablation. Bleeding and technical problems with the equipment occurred in 1
      patient each. Multivariable analysis revealed previous cardiovascular disease and
      needle placement close to the celiac trunk associated with increased likelihood
      for cardiac events. CONCLUSIONS: Intraoperative cardiac adverse events are common
      during irreversible electroporation but rarely impair completion of the
      procedure.

PMID- 27712670
TI  - Insecure times? Workers' perceived job and labor market security in 23 OECD
      countries.
AB  - By examining the association between employees' perceptions of job security and
      central labor market policies and characteristics, this paper seeks to understand
      the mechanisms through which institutions generate confidence and positive
      expectations among individuals regarding their economic future. The analyses
      distinguish between different facets of perceived job security and different
      institutional mechanisms. My multilevel analyses of a data set that contains
      information on 12,431 individuals and 23 countries show that some labor market
      policies and characteristics are more likely than others to provide workers with
      subjective security. Unemployment assistance in particular is an effective means
      of reducing workers' worries about job loss. Dismissal protection, by contrast,
      only unleashes its psychologically protective effects under certain conditions.
      The paper's main conclusion is that the effectiveness of policies varies and that
      different types of labor market institutions serve as complements rather than as
      substitutes.

PMID- 27712671
TI  - The exclusion from welfare benefits: Resentment and survey attrition in a
      randomized controlled trial in Mexico.
AB  - Public policy programs must often impose limits on who may be eligible for
      benefits. Despite research on the impact of exclusion in developed countries,
      there is little evidence on how people react to being excluded from benefits in
      developing societies. Utilizing repeated waves of data from an experimental
      evaluation of Mexico's foundational PROGRESA antipoverty program, we examine the
      impact of exclusion and distinguish two separate forms. "Statistical exclusion"
      occurs where determination of benefits is based on randomized assignment to a
      treatment and control group. "Needs-based exclusion" occurs when benefits
      programs are designed to be selective rather than universal, basing eligibility
      on characteristics, like relative poverty, that are difficult to measure simply
      and accurately. Focusing on temporal variation in survey non-response as our
      behavioral outcome, we show that needs-based exclusion has much greater negative
      effects on continued participation than statistical exclusion. We also show that
      these effects are concentrated among the wealthy, that is, those furthest from
      the eligibility cut-off line. These findings reinforce general concerns about the
      validity of evaluation studies when incentives are at work. We discuss both the
      behavioral explanations that might underlie these findings as well as some
      potential approaches to reduce threats to evaluation validity.

PMID- 27712672
TI  - Life satisfaction, ethnicity and neighbourhoods: Is there an effect of
      neighbourhood ethnic composition on life satisfaction?
AB  - Immigrants and ethnic minorities tend to have lower life satisfaction than
      majority populations. However, current understanding of the drivers of these gaps
      is limited. Using a rich, nationally representative data set with a large sample
      of ethnic minorities and matched neighbourhood characteristics, we test whether
      first and second generation minorities experience lower life satisfaction once
      accounting for compositional differences and whether, specifically, neighbourhood
      deprivation impacts their wellbeing. We further investigate whether a larger
      proportion of own ethnic group in the neighbourhood improves satisfaction. We
      find life satisfaction is lower among ethnic minorities, and especially for the
      second generation, even controlling for individual and area characteristics.
      Neighbourhood concentration of own ethnic group is, however, associated with
      higher life satisfaction for Black Africans and UK born Indians and Pakistanis.
      The effect for Black Africans may stem from selection into areas, but findings
      for Indians and Pakistanis are robust to sensitivity tests.

PMID- 27712673
TI  - How the macroeconomic context impacts on attitudes to immigration: Evidence from
      within-country variation.
AB  - This study investigates the effects of the macroeconomic context on attitudes to
      immigration. Earlier studies do in some cases not provide significant empirical
      support for the existence of important such effects. In this article it is argued
      that this lack of consistent evidence is mainly due to the cross-national setup
      of these studies being vulnerable to estimation bias caused by country-specific
      factors. The present study instead analyzes attitude variation within countries
      over time. The results provide firm empirical support in favor of macroeconomic
      variation importantly affecting attitudes to immigration. As an illustration, the
      estimates indicate that the number of individuals in the average European country
      in 2012 who were against all immigration from poorer countries outside Europe was
      40% higher than it would have been if macroeconomic conditions in that year had
      been as good as they were in 2006.

PMID- 27712674
TI  - Context effects and the temporal stability of stated preferences.
AB  - In stated preference studies it is assumed that individuals' answers reflect true
      preferences and are stable over time. We test these two assumptions of validity
      and reliability using as an example a choice experiment study on ethical
      consumption that measures preferences for a Peace Product jointly produced by
      Israeli and Palestinian producers as well as for organic products. In a web
      survey conducted in Germany, we investigate the validity assumption by
      manipulating the question context and presenting one group of respondents with
      questions on anti-Semitic and anti-Arabic attitudes before the choice tasks, and
      presenting another group with these questions after the choice tasks. In order to
      test the assumption of temporal stability, the same experimental set-up was
      repeated in a second survey based on a new sample ten months after the first.
      However, prior to the second survey an external event, a major violent dispute
      between Israelis and the Palestinians occurred. Overall, we find evidence for a
      context effect but not for temporal instability. In both surveys, the placement
      of the attitudinal questions before the choice tasks has a positive effect on the
      valuation of products from Israel, Palestinian products and the Peace Product
      (i.e. a directional context effect). The respondents seem to act according to an
      anti-discrimination norm. In line with this reasoning, we find an attention shift
      caused by the attitudinal questions. Organic products are valued much less
      positively if discriminatory attitudes are surveyed before the choice tasks.
      Furthermore, despite the violent dispute, stated preferences are very stable over
      time. This indicates high reliability of stated preference studies and encourages
      the use of study results by private and public decision makers.

PMID- 27712676
TI  - The state of domestic affairs: Housework, gender and state-level institutional
      logics.
AB  - Multi-level cross-national research consistently shows individual housework
      arrangements are structured by broader contexts of equality. Across this body of
      research, the United States is treated as a single entity. Yet, individual-level
      housework time may vary by state-to-state differences in institutional market,
      family and legislative logics. To test these relationships, we pair individual
      level data from the American Time Use Survey (2003-2012; aged 18 to 64 n =
      106,190) with three state-level indices - female labor force empowerment, family
      traditionalism and state government liberalism. For market institutional logics,
      we find wives and husbands spend more but mothers less time in housework in
      states where women have more labor market power. For family logics, we find
      mothers spend more and husbands less time in housework in more traditional
      states. For legislative logics, we find women and husbands spend more time in
      housework in more liberal states. Our results highlight the importance of state
      to-state institutional logics on individuals' housework time.

PMID- 27712675
TI  - Does higher education expansion promote educational homogamy? Evidence from
      married couples of the post-80s generation in Shanghai, China.
AB  - The expansion of higher education witnessed in many societies influences the
      pattern of educational assortative mating. Structural transition theory predicts
      growing educational homogamy due to increasing preference for highly-educated
      partners who become more widely available. In contrast, social closure theory
      suggests depressed educational homogamy because the inflation of the education
      elite circle fosters the openness of marriage market, reducing the preference for
      a highly-educated mate and increasing the penetrability across social-status
      boundaries. Capitalizing the survey data that are representative of the post-80s
      one-child generation collected in Shanghai, China, we test the hypotheses derived
      from the two theories. Empirical results suggest that, with increasing
      availability of highly educated individuals, the extent of educational homogamy
      by birth cohort reveals a U-shaped pattern. This U-shaped pattern demonstrates
      increasing levels of educational homogamy and lends support to structural
      transition theory.

PMID- 27712677
TI  - It takes two: A dyadic model of recruitment to civic activity.
AB  - Why are some people, but not others, asked to engage in civic activity? Rather
      than focus on the personal traits of either potential recruits or recruiters for
      this initial stage of recruitment, we develop and test a theoretical framework
      that emphasizes the importance of shared relationships and characteristics
      between those doing the recruiting and those being recruited. Specifically, the
      nature of interactions, overlapping community and associational space, status and
      value homophily, and strength and intimacy are assessed to explain differential
      recruitment among people's closest ties. Furthermore, unlike previous studies, we
      do so across three different forms of civic activity-blood donation, volunteer
      work, and political activism-allowing us to identify larger patterns in civic
      solicitation. Results from multilevel analyses of dyads reorganized from ego
      centric data of U.S. adults show that while certain personal traits of egos and
      alters remain significant, attributes of the dyad are equally, if not more,
      consequential for explaining variation in who gets asked to participate in civic
      activity. Importantly, while certain dyadic characteristics-such as romantic
      partnerships-promote recruitment to all three forms of civic activity, the
      effects of others-such as sex homophily-are unique to specific forms. Broadly
      speaking, our results indicate that some types of dyadic characteristics are more
      powerful than others and that there are important differences in how particular
      dimensions of social connections shape recruitment efforts across the specific
      activities of donating blood, volunteering time, and engaging in political
      activism.

PMID- 27712678
TI  - Donations and dependence: Individual contributor strategies in house elections.
AB  - Despite the importance of individual contributors to financing federal
      candidates, past work has largely neglected this crucial financial constituency
      in favor of research on corporate and trade political action committees (PACs).
      By contrast, in this study I offer the first analysis of aggregate contributions
      from the population of individual contributors to House candidates. Using an
      original big dataset constructed from over fifteen million Federal Election
      Commission (FEC) disclosure records, I identify individual contributors (rather
      than contributions) and trace the variation in their strategies across types of
      House candidates. I distinguish between frequent donors, who are theorized to
      have more contact with members of Congress, versus infrequent donors in these
      elections. I find evidence that the character of aggregate donations from repeat
      donors is more access-oriented even while controlling for other salient candidate
      characteristics. Funds from infrequent donors, in contrast, appear more
      ideologically motivated. By also examining the percentage of funds that House
      candidates receive from repeat donors, I show that the fundraising coalitions of
      candidates may reproduce reliance on more access-oriented, repeat donors despite
      the influx of dollars from infrequent donors. I suggest that my findings provide
      a persuasive case for re-evaluating the diversity of roles individual
      contributors play in the campaign finance system, and for systematically
      analyzing variation in contributor strategies.

PMID- 27712679
TI  - Socially organized sentiments: Exploring the link between religious density and
      protest mobilization, 1960-1995.
AB  - Extensive research has shown individual religiosity to have an impact upon U.S.
      protest participation. But very little work has examined the role of religious
      density in a community on the likelihood of protest mobilization. Our research
      links the religious density across 62 counties in New York State to various
      protest mobilization issues during the period of 1960-1995. In this research, we
      develop a theory of socially organized sentiments to examine religious influences
      on overall protest event mobilizations in local communities, a specific example
      of a more general theory that can link community structure to multiple forms of
      civic engagement. The impact of various religious traditions is assessed by using
      measures for the density of religious population per congregation of three
      religious traditions-Mainline Protestantism, Evangelical Protestantism and
      Catholicism. The analysis also assesses the likelihood of mobilization concerning
      four specific issues-African-American civil rights, gender, anti-nuclear/peace,
      and anti-poverty movements.

PMID- 27712680
TI  - Does the standard voluntary association question capture informal associations?
AB  - Sociologists have long been attentive to participation in associational life.
      Yet, despite being repeatedly cautioned to consider more informal groups, most
      researchers focus on participation in formal voluntary associations using
      national surveys with fixed group categories, such as the General Social Survey
      (GSS). In this paper, we use new GSS data on the names of the voluntary
      associations listed by respondents to evaluate whether voluntary association
      prompts capture or miss various types of informal associations. We code the
      formality of the associations listed by respondents and also compare to a new
      sample of bottom-up, informal voluntary associations. We demonstrate that some
      response categories adequately capture both formal and informal associations,
      e.g., sports groups. However, our results also suggest that the standard
      voluntary association question both omits entire categories of informal
      associations and omits some informal variants of associations within categories.
      In the tradition of Baumgartner and Walker (1988), Wuthnow (1994), and Wellman et
      al. (2001), we suggest that we may misunderstand citizen associations if we
      ignore informal associating.

PMID- 27712681
TI  - Risky sexual behavior of foreign and native-born women in emerging adulthood: The
      long reach of mother-daughter relationships in adolescence.
AB  - Parents' influence on young adult sexual behavior receives little attention
      compared to influence on adolescent behavior. Yet effective parenting should have
      lasting effects. Even fewer studies examine parents' influence on sexual behavior
      of both foreign and native-born young adults. Using the National Longitudinal
      Study of Adolescent to Adult Health (Add Health) Waves I (1994-95) and III (2001
      02), we examine longitudinal associations among mother-daughter relationship
      quality and nativity during adolescence and young adults' risky sexual behaviors
      of condom use at last intercourse, number of sexual partners, and STI diagnoses
      (N = 4460). Women, 18-26 years old, who had good mother-adolescent daughter
      relationships have fewer partners and STIs in the past year. Second generation
      women have worse mother-adolescent daughter relationships, compared to third
      generation. Relationship quality does not explain associations between nativity
      and risky behavior. Lasting associations between relationship quality and risk
      behaviors suggest that reproductive health interventions should enhance mother
      adolescent relationships.

PMID- 27712682
TI  - Home sweet home? Home physical environment and inflammation in children.
AB  - The home environment includes important social and physical contexts within which
      children develop. Poor physical home environments may be a potential source of
      stress for children through difficult daily experiences. Using a sub-sample from
      the Los Angeles Family and Neighborhood Survey (N = 425), we consider how the
      home physical environment affects stress-related immune system dysregulation in
      children ages 3-18 years. Results indicated that children in poorer quality homes
      had higher inflammation (measured by C-reactive protein). The associations were
      particularly strong for younger children. We also found that part of the home
      physical environment association with CRP worked through increased risk of
      obesity for children living in low-quality homes. Future research should assess
      how home physical environments could be improved to reduce stress and improve
      health outcomes in children.

PMID- 27712683
TI  - Child support and mixed-status families an analysis using the Fragile Families
      and Child Wellbeing Study.
AB  - A large body of literature documents the importance of child support for
      children's wellbeing, though little is known about the child support behaviors of
      mixed-status families, a large and rapidly growing population in the United
      States. In this paper, we use data from the Fragile Families and Child Wellbeing
      Study to investigate the impact of citizenship status on formal and informal
      child support transfers among a nationally representative sample of parents who
      have citizen children. Probit regression models and propensity score matching
      (PSM) estimators show that mixed-status families are significantly less likely to
      have child support orders and child support receipt compared to their citizen
      counterparts. We found that mothers' knowledge of the child support system
      increases the probability of establishing paternity. However, cultural
      differences in knowledge of and perception about the U.S. child support system
      between mixed-status families and citizen families do not have an impact on the
      probability of getting a child support order, child support receipt, or in-kind
      child support. Rather, institutional factors such as collaborations between
      welfare agencies and child support enforcement agencies as well as state child
      support enforcement efforts have a significant impact on formal child support
      outcomes. The results are robust against different model specifications, measure
      constructions, and use of datasets. These findings have important policy
      implications for policy makers and researchers interested in reducing child
      poverty in complex family structures and underscore the need to revisit child
      support policies for mixed-status families.

PMID- 27712684
TI  - Tethered lives: A couple-based perspective on the consequences of parenthood for
      time use, occupation, and wages.
AB  - Prior research on parenthood effects has typically used single-sex models and
      estimated average effects. By contrast, we estimate population-level variability
      in partners' changes in housework hours, paid work hours, occupation traits, and
      wages after becoming parents, and we explore whether one partner's adjustment
      offsets or supplements the other's. We find tradeoffs between spouses on paid
      work adjustments to parenthood, but complementarity in adjustments to housework
      hours, occupation traits, and wages. The effect of parenthood on wives' behaviors
      is larger and more variable than on husbands' behaviors in every domain. The
      modest variation between husbands in work responses to parenthood explains little
      of the variation in the motherhood penalty, while variation in wives' own
      behaviors plays a larger role. We refer to this pattern as tethered autonomy:
      variation across American couples in work responses to parenthood is shaped
      primarily by variation in wives' adjustments, while husbands' work acts largely
      as a fixed point.

PMID- 27712686
TI  - Displacement in new economy labor markets: Post-displacement wage loss in high
      tech versus low tech cities.
AB  - While scholars and politicians tout education as the salve to employment
      disruptions, we argue that the geography of the new economy, and the social
      closure mechanisms that geography creates, may be just as important as
      individuals' characteristics for predicting post-displacement wage loss (or
      gain). We use data from the 2012 Displaced Workers ement of the Current
      Population Survey and from the 2010 United States Census to test hypotheses
      linking local labor markets in different industrial contexts to post-displacement
      wage loss. Our results point to age as a closure mechanism, and to the partially
      protective effect of education in high-tech versus low-tech economic sectors.
      This study is the first to use national level data to examine how employment in
      high-tech cities influences post-displacement wages. These findings are relevant
      both for theorizing about the new economy and for public policy.

PMID- 27712685
TI  - Factors associated with two types of child custody loss among a sample of African
      American mothers: A novel approach.
AB  - African American families are overrepresented in the Child Welfare System;
      however, extant research on this phenomenon has (1) focused mostly on Caucasian
      or mixed-race samples and (2) has not examined informal custody arrangements
      alongside official child custody loss. This research addresses these gaps in the
      literature by examining factors associated with both official and informal child
      custody loss among a sample of African American mothers. Multinomial regression
      results show that having ever been incarcerated following a conviction increases
      the odds of experiencing both types of custody loss relative to no loss.
      Additionally, mother's experiences of childhood victimization increase the
      likelihood of informal custody loss relative to no loss, while being older, past
      year homelessness, number of minor children, being lesbian or bisexual,
      crack/cocaine use, and more family social support increase the odds of official
      loss versus no loss. Finally, increases in social support from friends decrease
      the odds of official loss. Implications are discussed.

PMID- 27712688
TI  - Segregation by race and income in the United States 1970-2010.
AB  - A systematic analysis of residential segregation and spatial interaction by
      income reveals that as income rises, minority access to integrated neighborhoods,
      higher levels of interaction with whites, and more affluent neighbors also
      increase. However, the income payoffs are much lower for African Americans than
      other groups, especially Asians. Although Hispanics and Asians have always
      displayed declining levels of minority-white dissimilarity and rising levels of
      minority-white interaction with rising income, income differentials on these
      outcomes for blacks did not appear until 1990 and since then have improved at a
      very slow pace. Given their higher overall levels of segregation and income's
      limited effect on residential attainment, African Americans experience less
      integration, more neighborhood poverty at all levels of income compared to other
      minority groups. The degree of black spatial disadvantage is especially acute in
      the nation's 21 hypersegregated metropolitan areas.

PMID- 27712689
TI  - Residential segregation: The mitigating effects of past military experience.

PMID- 27712690
TI  - Altering the life course: Military service and contact with the criminal justice
      system.
AB  - Using data taken from the 1997 National Longitudinal Survey of Youth, we examine
      the relationship between military service and contact with the criminal justice
      system. Drawing on the life course concept of a turning point, we show that
      military service does little to affect the risk of being arrested or being
      convicted of crimes involving violence or destructive behavior, while at the same
      time significantly reducing the risk of being arrested or being convicted of non
      violent crimes. We find no evidence that service in a combat zone alters these
      relationships. Our results demonstrate how participation in a large-scale
      institution can serve as a turning point, altering the life course trajectories
      of young persons.

PMID- 27712687
TI  - Risk factors and outcomes of chronic sexual harassment during the transition to
      college: Examination of a two-part growth mixture model.
AB  - A two-part latent growth mixture model was implemented in order to examine
      heterogeneity in the growth of sexual harassment (SH) victimization in college
      and university students, and the extent to which SH class membership explains
      substance use and mental health outcomes for certain groups of students.
      Demographic risk factors, mental health, and substance use were examined as they
      related to chronically experienced SH victimization. Incoming freshmen students
      (N = 2855; 58% female; 54% White) completed a survey at five time points. In
      addition to self-reporting gender, race, and sexual orientation, students
      completed measures of sexual harassment, anxiety, depression, binge drinking, and
      marijuana use. Overall, self-reported SH declined upon college entry, although
      levels rebounded by the third year of college. Results also supported a two-class
      solution (Infrequent and Chronic) for SH victimization. Being female, White, and
      a sexual minority were linked to being classified into the Chronic (relative to
      the Infrequent) SH class. In turn, Chronic SH class membership predicted greater
      anxiety, depression, and substance use, supporting a mediational model.

PMID- 27712691
TI  - Reversing welfare reform? Immigrant restoration efforts and food stamp receipt
      among Mexican immigrant families.
AB  - The safety net that immigrants face today differs significantly from the
      immediate post-Welfare Reform era in terms of eligibility and economic context.
      To inform debates on immigrant access to the safety net, this paper examines
      implications of the 2002 Farm Security and Rural Investment Act, which restored
      food stamp eligibility to nearly two-thirds of immigrants who lost eligibility
      under Welfare Reform. Using data from the 1995-2013 Current Population Survey and
      a difference-in-difference design, I examine how restoration efforts have
      influenced food stamp participation and food insecurity rates among low-income
      Mexican immigrant households with children. I then examine trends in food stamp
      receipt across policy and economic changes since Welfare Reform. Overall, results
      suggest that immigrant restoration efforts have reversed some but not all of the
      negative consequences of Welfare Reform and that immigrant households' use of
      food stamps has increased, particularly in the wake of the Great Recession.

PMID- 27712692
TI  - From the Co-Editors-In-Chief.

PMID- 27712693
TI  - Decision Modeling for Cost-Utility Analysis.

PMID- 27712694
TI  - Response to Editorial: Estimating Health-State Utility for Economic Models in
      Clinical Studies: An ISPOR Good Research Practices Task Force Report.

PMID- 27712695
TI  - Estimating Health-State Utility for Economic Models in Clinical Studies: An ISPOR
      Good Research Practices Task Force Report.
AB  - Cost-utility models are increasingly used in many countries to establish whether
      the cost of a new intervention can be justified in terms of health benefits.
      Health-state utility (HSU) estimates (the preference for a given state of health
      on a cardinal scale where 0 represents dead and 1 represents full health) are
      typically among the most important and uncertain data inputs in cost-utility
      models. Clinical trials represent an important opportunity for the collection of
      health-utility data. However, trials designed primarily to evaluate efficacy and
      safety often present challenges to the optimal collection of HSU estimates for
      economic models. Careful planning is needed to determine which of the HSU
      estimates may be measured in planned trials; to establish the optimal
      methodology; and to plan any additional studies needed. This report aimed to
      provide a framework for researchers to plan the collection of health-utility data
      in clinical studies to provide high-quality HSU estimates for economic modeling.
      Recommendations are made for early planning of health-utility data collection
      within a research and development program; design of health-utility data
      collection during protocol development for a planned clinical trial; design of
      prospective and cross-sectional observational studies and alternative study
      types; and statistical analyses and reporting.

PMID- 27712696
TI  - When Future Change Matters: Modeling Future Price and Diffusion in Health
      Technology Assessments of Medical Devices.
AB  - BACKGROUND: Health technology assessments (HTAs) that take account of future
      price changes have been examined in the literature, but the important issue of
      price reductions that are generated by the reimbursement decision has been
      ignored. OBJECTIVES: To explore the impact of future price reductions caused by
      increasing uptake on HTAs and decision making for medical devices. METHODS: We
      demonstrate the use of a two-stage modeling approach to derive estimates of
      technology price as a consequence of changes in technology uptake over future
      periods on the basis of existing theory and supported by empirical studies. We
      explore the impact on cost-effectiveness and expected value of information
      analysis in an illustrative example on the basis of a technology in development
      for preterm birth screening. RESULTS: The application of our approach to the case
      study technology generates smaller incremental cost-effectiveness ratios compared
      with the commonly used single cohort approach. The extent of this reduction in
      the incremental cost-effectiveness ratio depends on the magnitude of the modeled
      price reduction, the speed of diffusion, and the length of the assumed technology
      life horizon. Results of value of information analysis are affected through
      changes in the expected net benefit calculation, the addition of uncertain
      parameters, and the diffusion-adjusted estimate of the affected patient
      population. CONCLUSIONS: Because modeling future changes in price and uptake has
      the potential to affect HTA outcomes, modeling techniques that can address such
      changes should be considered for medical devices that may otherwise be rejected.

PMID- 27712697
TI  - International Experiences in Quantitative Benefit-Risk Analysis to Support
      Regulatory Decisions.

PMID- 27712699
TI  - Patient-Focused Benefit-Risk Analysis to Inform Regulatory Decisions: The
      European Union Perspective.
AB  - Regulatory decisions are often based on multiple clinical end points, but the
      perspectives used to judge the relative importance of those end points are
      predominantly those of expert decision makers rather than of the patient.
      However, there is a growing awareness that active patient and public
      participation can improve decision making, increase acceptance of decisions, and
      improve adherence to treatments. The assessment of risk versus benefit requires
      not only information on clinical outcomes but also value judgments about which
      outcomes are important and whether the potential benefits outweigh the harms.
      There are a number of mechanisms for capturing the input of patients, and
      regulatory bodies within the European Union are participating in several
      initiatives. These can include patients directly participating in the regulatory
      decision-making process or using information derived from patients in empirical
      studies as part of the evidence considered. One promising method that is being
      explored is the elicitation of "patient preferences." Preferences, in this
      context, refer to the individual's evaluation of health outcomes and can be
      understood as statements regarding the relative desirability of a range of
      treatment options, treatment characteristics, and health states. Several methods
      for preference measurement have been proposed, and pilot studies have been
      undertaken to use patient preference information in regulatory decision making.
      This article describes how preferences are currently being considered in the
      benefit-risk assessment context, and shows how different methods of preference
      elicitation are used to support decision making within the European context.

PMID- 27712698
TI  - Regulatory Decision Making in Canada-Exploring New Frontiers in Patient
      Involvement.
AB  - Recent legislative amendments aim to enhance the transparency of the regulatory
      review processes about drugs, and provide public information about Health
      Canada's review decisions. There is also growing recognition of the value, with
      respect to regulatory benefit-risk assessment, of information that could be
      gathered from patients-the direct users of these products. Patients can provide
      unique insights into practical aspects of living with their disease and its
      treatments-as well as gaps in treatment needs. An enhanced understanding of
      patients' experiences and perspectives can contribute directly to better-informed
      decision making about these products by regulators. Health Canada is currently
      exploring and examining the most effective ways to collect and consider patient
      input in the evaluation of therapeutic products. As part of this process, Health
      Canada is assessing the suitability of other existing models through
      environmental scans, discussions with other health authorities, and pilot
      projects. Lessons learned from these models can inform best practices and
      opportunities for patient involvement when designing a model to meet Canada's
      needs and context. Health Canada launched a Patient Involvement Pilot Project in
      2014 to simulate how input from patients, their caregivers, health care
      professionals, and patient groups could be collected and incorporated in the drug
      submission review process. This ongoing experience and continuous learning will
      define better how to incorporate patient input into benefit-risk assessment and
      regulatory decision making throughout the life cycle of therapeutic products in
      Canada.

PMID- 27712700
TI  - Patient Preferences in Regulatory Benefit-Risk Assessments: A US Perspective.
AB  - Demands for greater transparency in US regulatory assessments of benefits and
      risks, together with growing interest in engaging patients in Food and Drug
      Administration regulatory decision making, have resulted in several recent
      regulatory developments. Although Food and Drug Administration's Center for Drug
      Evaluation and Research (CDER) and Center for Devices and Radiological Health
      (CDRH) have established patient-engagement initiatives, CDRH has proposed
      guidelines for considering quantitative data on patients' benefit-risk
      perspectives, while CDER has focused on a more qualitative approach. We summarize
      two significant studies that were developed in collaboration and consultation
      with CDER and CDRH. CDER encouraged a patient advocacy group to propose draft
      guidance on engaging patient and caregiver stakeholders in regulatory decision
      making for Duchenne muscular dystrophy. CDRH sponsored a discrete-choice
      experiment case study to quantify obese respondents' perspectives on "meaningful
      benefits." CDRH and CDER issued draft guidance in May and June 2015,
      respectively, on including patient-preference data in regulatory submissions.
      Both organizations face challenges. CDER is working on integrating qualitative
      data into existing evidence-based review processes and is exploring options for
      therapeutic areas not included on a priority list. CDRH has adopted an approach
      that requires patient-preference data to satisfy standards of valid scientific
      evidence. Although that strategy could facilitate integrating patient
      perspectives directly with clinical data on benefits and harms, generating such
      data requires building capacity.

PMID- 27712701
TI  - A Framework for Incorporating Patient Preferences Regarding Benefits and Risks
      into Regulatory Assessment of Medical Technologies.
AB  - BACKGROUND: In response to 2012 guidance in which the US Food and Drug
      Administration's (FDA) Center for Devices and Radiological Health (CDRH) stated
      the importance of patient-centric measures in regulatory benefit-risk
      assessments, the Medical Device Innovation Consortium (MDIC) initiated a project.
      The project was used to develop a framework to help the Food and Drug
      Administration (FDA) and industry sponsors understand how patient preferences
      regarding benefit and risk might be integrated into the review of innovative
      medical devices. METHODS: A public-private partnership of experts from medical
      device industry, government, academia and non-profits collaborated on development
      of the MDIC patient centered benefit-risk framework. RESULTS: The MDIC Framework
      examines what patient preference information is and the potential use and value
      of patient preference information in the regulatory process and across the
      product development life cycle. The MDIC Framework also includes a catalog of
      patient preference assessment methods and an agenda for future research to
      advance the field. CONCLUSIONS: This article discusses key concepts in patient
      preference assessment of particular importance for regulators and researchers
      that are addressed in the MDIC Framework for patient centered benefit-risk
      assessment as well as the unique public-private collaboration that led its
      development.

PMID- 27712702
TI  - Developing a Patient-Centered Benefit-Risk Survey: A Community-Engaged Process.
AB  - OBJECTIVES: To provide a community-engaged process to inform the design of a
      stated-preferences experiment. The process involved integrating patients and
      caregivers of people with Duchenne/Becker muscular dystrophy, advocates,
      clinicians, and the sponsor in conceptualizing and developing a benefit-risk
      survey on the basis of phase III trial results. METHODS: Our community-engagement
      process for the development of a stated-preference survey included a set of five
      guiding principles with a foundation in the principles of community-engaged
      research. Engagement efforts were carried out through an informal network of
      three committees. Members of the leadership, stakeholder, and review committees
      comprised patients, caregivers, clinicians, advocacy leadership, and industry
      representatives. RESULTS: Committee members participated in 15 hours of formal
      engagement including interviews and conference calls that ranged from 45 to 90
      minutes, plus additional less-formal ad hoc communication. Committees comprised
      20 individuals across three committees including adults with DMD (n = 6), parents
      of children with DMD (n = 6), clinicians (n = 3), members of research and
      advocacy organizations (n = 4), and an industry representative (n = 1). Community
      engagement informed attribute selection, survey length, word choice, and
      eligibility criteria. Challenges in the process included managing diverse
      stakeholder perspectives, time requirements, and the inherent tension between
      outcomes used in clinical trials versus attributes that correspond to patient-
      and family-relevant outcomes. CONCLUSIONS: We demonstrated how community
      engagement can successfully influence study design to support the design of a
      relevant survey instrument that is ethical, acceptable, meaningful to the
      community, and enhances patient-centered benefit-risk assessment for regulatory
      decision making.

PMID- 27712703
TI  - Attribute Development Using Continuous Stakeholder Engagement to Prioritize
      Treatment Decisions: A Framework for Patient-Centered Research.
AB  - OBJECTIVES: To develop a methodological approach for selecting, validating, and
      prioritizing attributes for health care decision making. METHODS: Participants (n
      = 48) were recruited from community support groups if they had a child aged 26
      years or younger diagnosed with a coexisting mental health condition and
      cognitive impairment. Six in-depth interviews eliciting care management
      experiences were transcribed and coded into themes following the principles of
      grounded theory and the constant comparative method. Six focus groups involving
      42 participants assessed the relevance, priority, and meaning and inter
      relationship among the themes. The positive predictive value and sensitivity
      assessed agreement on thematic meaning. A final list was selected from the top
      priorities with good agreement as candidate attributes. Attribute levels
      reflecting the range of experiences in care management decisions emerged from the
      verbatim passages within each coded theme. RESULTS: Participants were the child's
      mother (73%), white (77%), married (69%), and on average 48 years old. The
      children were on average 14 years old; 44% had an intellectual disability, 25%
      had autism, and more than half had anxiety or attention-deficit/hyperactivity
      disorder. All 14 attributes identified from the in-depth interviews were deemed
      relevant. The positive predictive value exceeded 90%, and the sensitivity ranged
      from 64% to 89%. The final set of attributes formed the framework for care
      management decisions consisting of six attributes (medication, behavior,
      services, social, treatment effects, and school) each with three levels.
      CONCLUSIONS: A systematic approach grounded in qualitative methods produced a
      framework of relevant, important, and actionable attributes representing
      competing alternatives in clinical decisions.

PMID- 27712704
TI  - Measuring High-Risk Patients' Preferences for Pharmacogenetic Testing to Reduce
      Severe Adverse Drug Reaction: A Discrete Choice Experiment.
AB  - OBJECTIVES: To investigate patient preferences and willingness to pay (WTP) for a
      genetic test that can reduce the risk of life-threatening adverse drug reactions
      (ADRs). We hypothesize that test features (risk of developing the adverse
      reaction with and without testing, test cost, and treatment cost) and the choice
      context (physician recommendation and the most common choice made by peer
      patients) will influence choices. METHODS: A discrete choice experiment was
      conducted in which 189 patients at high risk for gout were asked to choose
      between treatment options that varied along key attributes. A latent class logit
      model was used to analyze the choice data and test the hypotheses. RESULTS: We
      identified two classes of patients: the risk-averse class and the cost-conscious
      class. The WTP to reduce the risk of life-threatening ADRs from 1 out of 600 to 1
      out of 1 million was SGD1215 in the risk-averse class. In contrast, in the cost
      conscious class, the WTP was insensitive to the extent of risk reduction.
      Overall, the predicted take-up rate for the test is 65% at a price of SGD400. If
      the test was recommended by a physician or was chosen by most of the patients,
      the take-up rate for the test would increase by 8.5 and 1.5 percentage points,
      respectively. CONCLUSIONS: There is a potentially large demand for genetic tests
      that could reduce the risk of life-threatening ADRs. Physician recommendations
      and providing information on the choices of others are powerful influences on
      demand, even more so than moderate price reductions.

PMID- 27712705
TI  - First and Foremost Battle the Virus: Eliciting Patient Preferences in Antiviral
      Therapy for Hepatitis C Using a Discrete Choice Experiment.
AB  - BACKGROUND: There has been tremendous progress regarding treatment options for
      hepatitis C virus (HCV) infection. Several interferon-free regimens are awaiting
      regulatory approval. These innovations promise substantial reductions in the
      burden of disease and side effects as well as a decrease in treatment duration.
      OBJECTIVES: The aim of this quantitaitive study was to elicit patient preferences
      for attributes of innovative antiviral therapies for hepatitis C. METHODS: A
      systematic literature search and 14 semi-structured interviews were performed,
      resulting in eight patient-relevant characteristics. For the discrete choice
      experiment, an experimental design (3*3 + 5*6) was generated using Ngene
      software. The survey was conducted in August 2014 through computer-assisted
      personal interviews. The data were effects-coded in a random parameter logit
      estimation. RESULTS: Participants were patients with HCV (N = 561; 58.1% men) in
      different treatment states. The analysis revealed a predominance of the attribute
      "reaching sustained virological response." When considering confidence intervals,
      the results showed three different preference ranks. At first place was
      "sustained virological response" (level difference [LD] 3.98), second was
      "anemia" (LD 1.10), followed by "number of interferon injections" (LD 0.92),
      "rash" (LD 0.82), "nausea and/or diarrhea" (LD 0.79), and "duration of antiviral
      therapy" (LD 0.78). The last position was occupied by both "tiredness/fatigue"
      (LD 0.31) and "headache" (LD 0.34). CONCLUSIONS: From the patients' point of
      view, sustained virological response is the most essential criterion for choosing
      an HCV therapy. It was ranked at the highest, dominating all side effects and
      modes of administration. Furthermore, this study proved that patients consider
      both the probability of occurrence and the severity of treatment-induced side
      effects. Results clearly point to valuation of probabilities that is separate
      from that of severity.

PMID- 27712707
TI  - The Capability Approach: A Critical Review of Its Application in Health
      Economics.
AB  - The capability approach is an approach to assessing well-being developed by
      Amartya Sen. Interest in this approach has resulted in several attempts to
      develop questionnaires to measure and value capability at an individual level in
      health economics. This commentary critically reviews the ability of these
      questionnaires to measure and value capability. It is argued that the method used
      in the questionnaires to measure capability will result in a capability set that
      is an inaccurate description of the individual's true capability set. The
      measured capability set will either represent only one combination and ignore the
      value of choice in the capability set, or represent one combination that is not
      actually achievable by the individual. In addition, existing methods of valuing
      capability may be inadequate because they do not consider that capability is a
      set. It may be practically more feasible to measure and value capability
      approximately rather than directly. Suggestions are made on how to measure and
      value an approximation to capability, but further research is required to
      implement the suggestions.

PMID- 27712706
TI  - Impact of Treatment Subsidies and Cash Payouts on Treatment Choices at the End of
      Life.
AB  - OBJECTIVES: To examine the extent to which financial assistance, in the form of
      subsidies for life-extending treatments (LETs) or cash payouts, distorts the
      demand for end-of-life treatments. METHODS: A discrete choice experiment was
      administered to 290 patients with cancer in Singapore to elicit preferences for
      LETs and only palliative care (PC). Responses were fitted to a latent class
      conditional logistic regression model. We also quantified patients' willingness
      to pay to avoid and willingness to accept a less effective LET or PC-only. We
      then simulated the effects of various LET subsidy and cash payout policies on
      treatment choices. RESULTS: We identified three classes of patients according to
      their preferences. The first class (26.1% of the sample) had a strong preference
      for PC and were willing to give up life expectancy gains and even pay for
      receiving only PC. The second class (29.8% of the sample) had a strong preference
      for LETs and preferred to extend life regardless of cost or quality of life. The
      final class (44.1% of the sample) preferred LETs to PC, but actively traded off
      costs and length and quality of life when making end-of-life treatment choices.
      Policy simulations showed that LET subsidies increase demand for LETs at the
      expense of demand for PC, but an equivalent cash payout was not shown to distort
      demand. CONCLUSIONS: Patients with cancer have heterogeneous end-of-life
      preferences. LET subsidies and cash payouts have differing effects on the use of
      LETs. Policymakers should be mindful of these differences when designing health
      care financing schemes for patients with life-limiting illnesses.

PMID- 27712708
TI  - Patient Heterogeneity in Health Economic Decision Models for Chronic Obstructive
      Pulmonary Disease: Are Current Models Suitable to Evaluate Personalized Medicine?
AB  - OBJECTIVES: To assess how suitable current chronic obstructive pulmonary disease
      (COPD) cost-effectiveness models are to evaluate personalized treatment options
      for COPD by exploring the type of heterogeneity included in current models and by
      validating outcomes for subgroups of patients. METHODS: A consortium of COPD
      modeling groups completed three tasks. First, they reported all patient
      characteristics included in the model and provided the level of detail in which
      the input parameters were specified. Second, groups simulated disease
      progression, mortality, quality-adjusted life-years (QALYs), and costs for
      hypothetical subgroups of patients that differed in terms of sex, age, smoking
      status, and lung function (forced expiratory volume in 1 second [FEV1] %
      predicted). Finally, model outcomes for exacerbations and mortality for subgroups
      of patients were validated against published subgroup results of two large COPD
      trials. RESULTS: Nine COPD modeling groups participated. Most models included sex
      (seven), age (nine), smoking status (six), and FEV1% predicted (nine), mainly to
      specify disease progression and mortality. Trial results showed higher
      exacerbation rates for women (found in one model), higher mortality rates for men
      (two models), lower mortality for younger patients (four models), and higher
      exacerbation and mortality rates in patients with severe COPD (four models).
      CONCLUSIONS: Most currently available COPD cost-effectiveness models are able to
      evaluate the cost-effectiveness of personalized treatment on the basis of sex,
      age, smoking, and FEV1% predicted. Treatment in COPD is, however, more likely to
      be personalized on the basis of clinical parameters. Two models include several
      clinical patient characteristics and are therefore most suitable to evaluate
      personalized treatment, although some important clinical parameters are still
      missing.

PMID- 27712709
TI  - Cost-Effectiveness of Rotavirus Vaccination in France-Accounting for Indirect
      Protection.
AB  - BACKGROUND: Vaccination against rotavirus has shown great potential for reducing
      the primary cause of severe childhood gastroenteritis. Previous economic
      evaluations of rotavirus vaccination in France have not modeled the potential
      impact of vaccines on disease burden via reduced transmission. OBJECTIVE: To
      determine the cost-effectiveness of the introduction of pentavalent rotavirus
      vaccination into the French infant vaccination schedule. METHODS: We developed an
      age-structured model of rotavirus transmission calibrated to 6 years of French
      gastroenteritis incidence and vaccine clinical trial data. We evaluated the cost
      effectiveness of pentavalent rotavirus vaccination considering that 75% of
      infants would receive the three-dose vaccine course. RESULTS: Our model predicts
      that rotavirus vaccination will decrease rotavirus gastroenteritis incidence and
      associated clinical outcomes in vaccinated and unvaccinated individuals, delay
      the seasonal peak of infection, and increase the age of infection. From the
      societal perspective, our base-case scenario predicts that vaccination coverage
      would be cost-effective at ?115 or ?135 per vaccine course at ?28,500 and
      ?39,500/quality-adjusted life-year (QALY) gained, respectively, and suggests that
      almost 95% of the financial benefits will be recouped within the first 5 years
      following vaccination implementation. From the third-party payer perspective,
      incremental cost-effectiveness ratios ranged from ?12,500 to ?20,000/QALY,
      respectively. Our uncertainty analysis suggests that findings were sensitive to
      various assumptions including the number of hospitalizations, outpatient visits,
      and the extent of QALY losses per rotavirus episode. CONCLUSIONS: Introducing
      pentavalent rotavirus vaccination into the French infant vaccination schedule
      would significantly reduce the burden of rotavirus disease in children, and could
      be cost-effective under plausible conditions.

PMID- 27712710
TI  - Measuring Health and Broader Well-Being Benefits in the Context of Opiate
      Dependence: The Psychometric Performance of the ICECAP-A and the EQ-5D-5L.
AB  - BACKGROUND: Measuring outcomes in economic evaluations of social care
      interventions is challenging because both health and well-being benefits are
      evident. The ICEpop CAPability instrument for adults (ICECAP-A) and the five
      level EuroQol five-dimensional questionnaire (EQ-5D-5L) are measures potentially
      suitable for the economic evaluation of treatments for substance use disorders.
      Evidence for their validity in this context is, however, lacking. OBJECTIVES: To
      assess the construct validity of the ICECAP-A and the EQ-5D-5L in terms of
      convergent and discriminative validity and sensitivity to change on the basis of
      standard clinical measures (Clinical Outcomes in Routine Evaluation-Outcome
      Measure, Treatment Outcomes Profile, Interpersonal Support Evaluation List, Leeds
      Dependence Questionnaire, and Social Satisfaction Questionnaire). METHODS: A
      secondary analysis of pilot trial data for heroin users in opiate substitution
      treatment was conducted. Baseline convergence with clinical measures was assessed
      using the Pearson correlation coefficient. Discriminative validity was assessed
      using one-way analysis of variance and stepwise regressions. Sensitivity to
      changes in clinical indicators was assessed at 3 and 12 months using the
      standardized response mean statistic and parametric and nonparametric testing.
      RESULTS: Both measures had the same level of construct validity, except for
      clinical indicators of well-being, for which the ICECAP-A performed better. The
      ICECAP-A was sensitive to changes in both health and well-being indicators. The
      EQ-5D-5L had lower levels of sensitivity to change, and a ceiling effect (27%),
      particularly evident in the dimensions of self-care (89%), mobility (75%), and
      usual activities (72%). CONCLUSIONS: The findings support the construct validity
      of both measures, but the ICECAP-A gives more attention to broader impacts and is
      more sensitive to change. The ICECAP-A shows promise in evaluating treatments for
      substance use disorders for which recovery is the desired outcome.

PMID- 27712711
TI  - Comparison of Daily versus Weekly Recording of Gastroesophageal Reflux Disease
      Symptoms in Patients with a Partial Response to Proton Pump Inhibitor Therapy.
AB  - BACKGROUND: The Reflux Symptom Questionnaire electronic Diary (RESQ-eD) and the
      Reflux Symptom Questionnaire 7-day recall (RESQ-7) are versions of a patient
      reported outcome instrument that was developed and validated for measuring the
      frequency and intensity of symptoms in patients with gastroesophageal reflux
      disease (GERD) who have a partial response to proton pump inhibitor (PPI)
      therapy. OBJECTIVE: The aim of these analyses was to assess the ability of the
      RESQ-7 to reproduce findings based on RESQ-eD reports of the same symptoms.
      METHODS: These analyses are based on data from patients with GERD with a partial
      response to PPI (ClinicalTrials.gov identifier: NCT00703534). Participants
      completed the RESQ-eD twice daily for 7 days and the RESQ-7 on day 7. RESULTS:
      Data from 446 patients were available for these analyses. Symptom-level analyses
      showed that, for intensity, mean domain scores were higher for the RESQ-7 (range
      1.49-2.72) than for the RESQ-eD (range 1.45-2.57); for frequency, scores were
      lower for the RESQ-7 (range 2.58-4.82) than for the RESQ-eD (range 4.22-6.24).
      Correspondence analyses of RESQ-7 and RESQ-eD mean domain scores indicated
      excellent agreement for intensity (correlation-concordance coefficient 0.77-0.83)
      and fair agreement for frequency (correlation-concordance coefficient 0.40-0.58).
      Mean RESQ-eD subscale intensity scores for GERD symptoms were higher for symptoms
      experienced during the daytime than for those occurring at nighttime. Symptom
      recall was not associated with peak or recency effects. CONCLUSIONS: Patients
      with GERD slightly overestimated the intensity of their reflux symptoms and
      markedly underestimated the frequency on weekly recall compared with twice-daily
      reporting.

PMID- 27712712
TI  - Which Questionnaire Should Be Used to Measure Quality-of-Life Utilities in
      Patients with Acute Leukemia? An Evaluation of the Validity and Interpretability
      of the EQ-5D-5L and Preference-Based Questionnaires Derived from the EORTC QLQ
      C30.
AB  - OBJECTIVES: The aim of this study was to assess the validity and interpretability
      of different preference-based questionnaires (generic 5-level EuroQol five
      dimensional questionnaire [EQ-5D-5L], cancer-specific Quality of Life
      Questionnaire Preference-Based Measure, and European Organization of Randomized
      Controlled Trials 8 Dimension [EORTC-8D]) in patients with acute leukemia.
      METHODS: Patients who participated in Hemato-Oncologie voor Volwassenen Nederland
      (HOVON - the Haemato Oncology Foundation for Adults in the Netherlands) clinical
      trials between 1999 and 2011 at a single hospital were invited to complete the
      questionnaires. Interpretability was evaluated by the frequency of incomplete
      data and highest and lowest possible scores. Content validity was evaluated by
      exploring the health-related quality-of-life domains included in the
      questionnaires. Construct validity was assessed using correlations with other
      quality-of-life scales (EQ-visual analogue scale score and global quality-of-life
      scale of the EORTC Quality of Life Questionnaire) and ability to distinguish
      between patients with different health statuses. RESULTS: Questionnaires were
      returned by 89% (111 of 125) of the patients. Six to seven respondents did not
      return full questionnaires. Perfect health on the EQ-5D-5L was reported by 32
      respondents and many of them (N = 17) did report health problems on other
      questionnaires. All questionnaires were strongly correlated (range 0.61-0.78)
      with other quality-of-life scales and yielded substantially different utility
      values for patients with different health statuses. Nevertheless, the disease
      specific preference-based questionnaires showed greater discriminatory power.
      CONCLUSIONS: Although the Quality of Life Questionnaire Preference-Based Measure
      and the EORTC-8D appear to have better validity, this study does not provide any
      strong evidence against the use of the EQ-5D-5L for measuring quality-of-life
      utilities in acute leukemia. However, our findings need to be confirmed in larger
      longitudinal studies.

PMID- 27712713
TI  - Adherence to Self-Care Behaviors among Patients with Type 2 Diabetes-The Role of
      Risk Preferences.
AB  - OBJECTIVES: To examine whether the degree of risk aversion is associated with
      adherence to disease self-management among adults with type 2 diabetes. METHODS:
      This was a cross-sectional study of patients with type 2 diabetes (n = 408) aged
      21 to 70 years who presented for routine visits in the diabetes clinic at a
      university medical center in Beer-Sheva, Israel. The authors used validated
      questionnaires to estimate adherence, risk preferences, motivation, self
      efficacy, impulsivity, perceptions about the disease and the interpersonal
      process of care, and demographic and socioeconomic characteristics, in addition
      to retrieving data from computerized patient medical records of clinical
      indicators of disease severity. Multivariable linear and ordered-logit models
      examined predictors of adherence to each self-care behavior. RESULTS:
      Multivariable analyses revealed that, compared with others, risk-seeking patients
      reported lower general adherence (beta = -0.32; P <= 0.05), and specifically,
      lower adherence to healthful eating plan (beta = -0.48; P <= 0.1), consumption of
      low-fat food (beta = -0.47; P <= 0.1), exercise (beta = -0.73; P <= 0.05), blood
      glucose monitoring (beta = -0.69; P <= 0.05), and foot care (beta = -0.36; P <=
      0.1). Risk-seeking patients did not report lower consumption of fruits and
      vegetables (beta = -0.19; P > 0.1). Because 96% of the study population reported
      optimal adherence to medication, determinants of this behavior could not be
      analyzed. CONCLUSIONS: Risk preference is associated with adherence to self-care
      behaviors. Identifying risk seekers may enable practitioners to target these
      patients with tailored strategies to improve adherence, thus more efficiently
      allocating scarce health care resources.

PMID- 27712714
TI  - Development and Validation of Algorithms to Identify Statin Intolerance in a US
      Administrative Database.
AB  - OBJECTIVES: To develop and validate algorithms to define statin intolerance (SI)
      in an administrative database using electronic medical records (EMRs) as the
      reference comparison. METHODS: One thousand adults with one or more qualifying
      changes in statin therapy and one or more previous diagnoses of hyperlipidemia,
      hypercholesterolemia, or mixed dyslipidemia were identified from the Henry Ford
      Health System administrative database. Data regarding statin utilization,
      comorbidities, and adverse effects were extracted from the administrative
      database and corresponding EMR. Patients were stratified by cardiovascular (CV)
      risk. SI was classified as absolute intolerance or titration intolerance on the
      basis of changes in statin utilization and/or the occurrence of adverse effects
      and laboratory testing for creatine kinase. Measures of concordance (Cohen's
      kappa [kappa]) and accuracy (sensitivity, specificity, positive predictive value
      [PPV], and negative predictive value) were calculated for the administrative
      database algorithms. RESULTS: Half of the sample population was white, 52.9% were
      women, mean age was 60.6 years, and 35.7% were at high CV risk. SI was identified
      in 11.5% and 14.0%, absolute intolerance in 2.2% and 3.1%, and titration
      intolerance in 9.7% and 11.8% of the patients in the EMR and the administrative
      database, respectively. The algorithm identifying any SI had substantial
      concordance (kappa = 0.66) and good sensitivity (78.1%), but modest PPV (64.0%).
      The titration intolerance algorithm performed better (kappa = 0.74; sensitivity
      85.4%; PPV 70.1%) than the absolute intolerance algorithm (kappa = 0.40;
      sensitivity 50%; PPV 35.5%) and performed best in the high CV-risk group (n =
      353), with robust concordance (kappa = 0.73) and good sensitivity (80.9%) and PPV
      (75.3%). CONCLUSIONS: Conservative but comprehensive algorithms are available to
      identify SI in administrative databases for application in real-world research.
      These are the first validated algorithms for use in administrative databases
      available to decision makers.

PMID- 27712715
TI  - Financing a Cure for Diabetes in a Multipayer Environment.
AB  - BACKGROUND: Financing medical breakthroughs or cures is becoming increasingly
      challenging in the current fiscal environment. OBJECTIVES: In this paper, we
      develop the precise conditions needed for a financing mechanism, HealthCoin, to
      work between a private payer and Medicare, to incentivize the former to invest in
      breakthrough therapies or cures in the US. METHODS: We illustrate the valuation
      of such a currency for a cure of Type 2 diabetes. RESULTS: We show that without a
      HealthCoin, a private payer does not invest in the cure, a small fraction of the
      patients live up to age 65, Medicare pays for the full price of the cure at age
      65 and incurs net loss in returns over the elderly ages, and the manufacturer
      only sells cures for those who reach age 65. In contrast, a HealthCoin is
      feasible in this market, incentivizing the private payer to invest in the cure
      during the non-elderly ages and leading to Pareto improvements for all three
      stakeholders. CONCLUSIONS: Discussions around the applicability of HealthCoin for
      breakthrough therapies on the horizon, such as gene therapies for blindness and
      hemophilia B, and the feasibility of instituting such payments through new
      legislations or demonstration projects could be of great value.

PMID- 27712716
TI  - Increasing Patient Involvement in Drug Development.
AB  - BACKGROUND: To ensure the creation of treatments that maximize value at the
      lowest cost, all aspects of the health care system need to align with patient
      needs and preferences. Despite growing efforts to engage patients in research and
      regulatory activities, the pharmaceutical industry has yet to maximize patient
      involvement in the drug development process. OBJECTIVE: To gain a better
      understanding of the present state of patient involvement in drug development.
      METHODS: Through a semistructured interview methodology, we sought to identify
      opportunities, barriers, and examples of patient involvement in the drug
      development process. Telephone interviews were conducted with six senior leaders
      of evidence generation within the pharmaceutical industry and four patients.
      These interviews were supplemented with interviews with a research funder, a
      regulator, a patient advocacy group, and a caregiver. RESULTS: Although our
      interviewees spoke of the potential benefits of aligning research around the
      needs of patients, there were few examples they could share to suggest this was
      occurring at scale. A number of barriers were identified including the added
      burden associated with adverse event reporting, concerns about patient
      representativeness or their ability to participate in drug development
      conversations, and the costs in time and resources involved relative to returns
      on investment. CONCLUSIONS: As health care systems continue to evolve and
      establish patients as the primary stakeholder in their health care decision
      making, the pharmaceutical industry will need to be innovative to demonstrate the
      value of their products relative to the outcomes experienced by patients.
      Pharmaceutical companies should recognize the value of involving patients across
      the entire product life cycle and work to transform present perceptions and
      practices throughout their organizations.

PMID- 27712717
TI  - Did It Matter That the Cancer Drugs Fund Was Not NICE? A Retrospective Review.
AB  - BACKGROUND: The Cancer Drugs Fund (CDF) will have spent more than L1 billion
      between October 2010 and the introduction of reforms to its structure and
      operations in July 2016. There has been much more debate about the existence of
      the fund than about how it spent its substantial budget. It is important to
      undertake a retrospective examination of "where the money went" in light of the
      substantial reforms that will be introduced in 2016. OBJECTIVES: We review the
      means by which the CDF made recent funding decisions for cancer drugs to provide
      an assessment of the merits of the CDF "model" as a basis for allocation
      decisions. We assess the extent to which proposed reforms could overcome defects
      in the original CDF model of prioritization, and lessons for other countries.
      METHODS: We provide a narrative commentary on CDF's methods and processes since
      2014. We evaluate methods against best practice in cost-effectiveness analysis,
      and processes against the "accountability for reasonableness" framework. We
      comment on reforms to the fund. RESULTS: There are no grounds for concluding that
      the opportunity costs imposed on cancer patients were well evidenced, or the
      product of legitimate deliberative processes. We note that some of these issues
      will be addressed in the next incarnation of the fund, but the rationale for the
      fund's existence remains unconvincing. CONCLUSIONS: It is important and timely to
      debate how cancer drugs appraisal ought to be conducted to confront the
      consequences of CDF's model of appraisal. We conclude that it did matter that the
      CDF was not NICE.

PMID- 27712718
TI  - A Comprehensive Algorithm for Approval of Health Technologies With, Without, or
      Only in Research: The Key Principles for Informing Coverage Decisions.
AB  - BACKGROUND: The value of evidence about the performance of a technology and the
      value of access to a technology are central to policy decisions regarding
      coverage with, without, or only in research and managed entry (or risk-sharing)
      agreements. OBJECTIVES: We aim to outline the key principles of what assessments
      are needed to inform "only in research" (OIR) or "approval with research" (AWR)
      recommendations, in addition to approval or rejection. METHODS: We developed a
      comprehensive algorithm to inform the sequence of assessments and judgments that
      lead to different types of guidance: OIR, AWR, Approve, or Reject. This algorithm
      identifies the order in which assessments might be made, how similar guidance
      might be arrived at through different combinations of considerations, and when
      guidance might change. RESULTS: The key principles are whether the technology is
      expected to be cost-effective; whether the technology has significant
      irrecoverable costs; whether additional research is needed; whether research is
      possible with approval and whether there are opportunity costs that once
      committed by approval cannot be recovered; and whether there are effective price
      reductions. Determining expected cost-effectiveness is only a first step. In
      addition to AWR for technologies expected to be cost-effective and OIR for those
      not expected to be cost-effective, there are other important circumstances when
      OIR should be considered. CONCLUSIONS: These principles demonstrate that cost
      effectiveness is a necessary but not sufficient condition for approval. Even when
      research is possible with approval, OIR may be appropriate when a technology is
      expected to be cost-effective due to significant irrecoverable costs.

PMID- 27712719
TI  - Economic Impact of Integrated Care Models for Patients with Chronic Diseases: A
      Systematic Review.
AB  - OBJECTIVES: To assess the costs and potential financial benefits of integrated
      care models for patients with chronic diseases, that is, type 2 diabetes
      mellitus, schizophrenia, and multiple sclerosis, respectively. METHODS: A
      systematic search of the literature was performed using EMBASE, MEDLINE, and Web
      of Science. Studies that conducted a cost analysis, considered at least two
      components of the chronic care model, and compared integrated care with standard
      care were included. RESULTS: Out of 575 articles, 26 were included. Most studies
      examined integrated care models for type 2 diabetes mellitus (n = 18) and to a
      lesser extent for schizophrenia (n = 6) and multiple sclerosis (n = 2). Across
      the three disease groups, the incremental cost per patient per year ranged from -
      ?3860 to + ?613.91 (x- = - ?533.61 +/- ?902.96). The incremental cost for type 2
      diabetes mellitus ranged from - ?1507.49 to + ?299.20 (x- = - ?518.22 +/- +
      ?604.75), for schizophrenia from - ?3860 to + ?613.91 (x- = - ?677.21 +/- +
      ?1624.35), and for multiple sclerosis from - ?822 to + ?339.43 (x- = - ?241.29 +/
      + ?821.26). Most of the studies (22 of 26 [84.6%]) reported a positive economic
      impact of integrated care models: for type 2 diabetes mellitus (16 of 18
      [88.9%]), schizophrenia (4 of 6 [66.7%]), and multiple sclerosis (1 of 2 [50%]).
      CONCLUSIONS: In this systematic literature review, predominantly positive
      economic impacts of integrated care models for patients with chronic diseases
      were found.

PMID- 27712720
TI  - A Systematic Review of Health Economic Evaluation Studies Using the Patient's
      Perspective.
AB  - BACKGROUND: Patient-centered care has become increasingly important and relevant
      for informed health care decision making. OBJECTIVE: Our study aimed to perform a
      systematic review of health economic evaluation studies from the patient's
      perspective. METHODS: PubMed, EMBASE, and Cochrane Central databases were
      searched through May 2014 for cost-effectiveness, cost-utility, and cost-benefit
      studies using the patient's perspective in their analysis. The reporting quality
      of the studies was evaluated on the basis of Consolidated Health Economic
      Evaluation Reporting Standards. RESULTS: We identified 30 health economic
      evaluations using the patient's perspective, of which 7 were conducted in the
      United States, 9 in Europe, and 14 in Asian or other countries. Seventeen of 23
      health conditions evaluated were chronic in nature. Among 12 studies that
      justified the use of the patient's perspective, patient's financial burden
      associated with medical treatment was the most commonly cited rationale. A total
      of 29, 17, and 15 studies examined direct medical, direct nonmedical, and
      indirect costs, respectively. Seventeen studies also included societal,
      governmental or payer's, and/or provider's perspective(s) in their analyses.
      Based on Consolidated Health Economic Evaluation Reporting Standards, more than
      20% of the reporting items in these studies were either partially satisfied or
      not satisfied. CONCLUSIONS: There is a paucity of health economic evaluations
      conducted from the patient's perspective in the literature. For those studies
      using the patient's perspective, the true patient costs were not fully explored
      and study reporting quality was not optimal. With the increasing focus on patient
      centered outcomes in health policy research, more frequent use of the patient's
      perspective in economic studies should be advocated.

PMID- 27712721
TI  - Redox-electrodes for selective electrochemical separations.
AB  - Redox-active materials hold great promise as platforms for selective liquid-phase
      separations. In contrast to capacitive electrodes that rely purely on double
      layer charge for deionization, redox-modified electrodes can be used to control
      Faradaic reactions at the interface to selectively bind various charged and
      uncharged molecules, thus modulating surface interactions through electrochemical
      potential solely. These electrodes can be composed of a range of functional
      materials, from organic and organometallic polymers to inorganic crystalline
      compounds, each relying on its own distinct ion-exchange process. Often, redox
      electrochemical systems can serve as pseudocapacitors or batteries, thus offering
      an advantageous combination of adsorption selectivity and energy
      storage/recovery. This review summarizes redox-interfaces for electrosorption and
      release, outlines methods for preparation and synthesis, discusses the diverse
      mechanisms for interaction, and gives a perspective on the future of redox
      mediated separations.

PMID- 27712722
TI  - Editorial commentary.

PMID- 27712723
TI  - Autophagy in neurodegenerative diseases.

PMID- 27712725
TI  - Training in Multimodality CV Imaging: Is There an Inclusive Model?

PMID- 27712726
TI  - The Business We Are In.

PMID- 27712727
TI  - It's About the Patient...Duh!

PMID- 27712724
TI  - The Future of Cardiac Imaging: Report of a Think Tank Convened by the American
      College of Cardiology.
AB  - The American College of Cardiology's Executive Committee and Cardiovascular
      Imaging Section Leadership Council convened a discussion regarding the future of
      cardiac imaging among thought leaders in the field during a 2 day Think Tank.
      Participants were charged with thinking broadly about the future of imaging and
      developing a roadmap to address critical challenges. Key areas of discussion
      included: 1) how can cardiac imaging services thrive in our new world of value
      based health care? 2) Who is the cardiac imager of the future and what is the
      role of the multimodality imager? 3) How can we nurture innovation and research
      in imaging? And 4) how can we maximize imaging information and optimize outcomes?
      This document describes the proceedings of this Think Tank.

PMID- 27712728
TI  - Cystic Pancreatic Neoplasm Guidelines and the Importance of PubMed Search
      Effectiveness.

PMID- 27712729
TI  - Author's Reply.

PMID- 27712730
TI  - Should Incidental Simple Renal Cysts Be Considered Normal Variants and Ignored in
      Radiologic Reports? Review of a Proposed Framework.

PMID- 27712731
TI  - The Ability to Multitask Effectively While Ensuring That All Customers Understand
      That They Are the Priority.

PMID- 27712732
TI  - Utility of Intravascular Ultrasound in Percutaneous Revascularization of Chronic
      Total Occlusions: An Overview.
AB  - Intravascular ultrasound has been used for >20 years to guide percutaneous
      coronary intervention in different subsets of coronary lesions. During the last
      decade, the interest in percutaneous coronary intervention for chronic total
      occlusion (CTO) has increased dramatically, leading to high success rates.
      Failure of guidewire crossing is the most common reason for failed CTO attempts.
      Certain angiographic features, such as blunt proximal CTO cap, tortuosity, heavy
      calcification, and lack of visibility of path in the distal vessel, increase
      procedural difficulty. A better understanding of the behavior of the guidewire
      within the CTO segment may represent a key issue to achieve successful outcome.
      In this respect, intravascular ultrasound imaging might have potential roles in
      the recanalization of CTOs. In this paper, we focused on the usefulness and the
      applications of intravascular ultrasound imaging in percutaneous CTO
      recanalization, underlying its impact on clinical outcome.

PMID- 27712733
TI  - Prevention of Radial Artery Occlusion After Transradial Catheterization: The
      PROPHET-II Randomized Trial.
AB  - OBJECTIVES: The study sought to evaluate whether prophylactic ipsilateral ulnar
      artery compression during radial artery hemostasis could reduce the risk of
      radial artery occlusion (RAO). BACKGROUND: RAO after transradial access (TRA) is
      a structural complication of TRA. It limits future ipsilateral TRA and may cause
      transient pain. Maintaining radial artery flow during hemostasis reduces the
      incidence of acute RAO. Ipsilateral ulnar compression increases radial artery
      flow and could impact the incidence of RAO. METHODS: Three thousand patients
      undergoing diagnostic cardiac catheterization using TRA were randomized to
      receive either standard patent hemostasis protocol (Group I) or prophylactic
      ipsilateral ulnar compression in addition to patent hemostasis (Group II). Using
      plethysmography, radial artery patency was evaluated at the time of removal of
      the compression device as well as 24 h and 30 days after the procedure. The
      primary study endpoint was 30-day RAO. RESULTS: The primary endpoint, 30-day RAO,
      was significantly reduced in patients with patent hemostasis and prophylactic
      ulnar compression compared with standard patent hemostasis (0.9% vs. 3.0%; p =
      0.0001). Baseline patient and procedural characteristics were similar between the
      2 groups. RAO was significantly reduced by prophylactic ulnar compression at all
      time intervals (p < 0.0001). CONCLUSIONS: Prophylactic ipsilateral ulnar
      compression during radial artery hemostasis is an effective, simple, and
      inexpensive technique that lowers the risk of RAO after TRA.

PMID- 27712734
TI  - The PROPHET-II's Prophecy.

PMID- 27712735
TI  - Does Residual Thrombus After Aspiration Thrombectomy Affect the Outcome of
      Primary PCI in Patients With ST-Segment Elevation Myocardial Infarction?: An
      Optical Coherence Tomography Study.
AB  - OBJECTIVES: The aim of this study was to evaluate if residual thrombus burden
      after aspiration thrombectomy affects the outcomes of primary percutaneous
      coronary intervention in patients with ST-segment elevation myocardial infarction
      (STEMI). BACKGROUND: Recent studies failed to show clinical benefit of aspiration
      thrombectomy in STEMI patients. This might be due to insufficient removal of
      thrombus at the culprit lesion. METHODS: A total of 109 STEMI patients who
      underwent aspiration thrombectomy followed by stenting within 24 h from symptom
      onset were included. Optical coherence tomography was performed after
      thrombectomy to measure residual thrombus burden. Patients were divided into
      tertiles based on the amount of residual thrombus and the outcomes were compared.
      RESULTS: Myocardial no reflow, defined as TIMI (Thrombolysis In Myocardial
      Infarction) flow grade of <=2 and/or myocardial blush grade of <=1 after
      stenting, was more observed frequently in patients in the highest tertile
      compared with those in the lowest tertile (44.4% vs. 16.7%; p = 0.001). Patients
      in the highest tertile also had greater myocardial damage measured by creatine
      kinase MB compared with those in the lowest tertile (p = 0.002). CONCLUSIONS:
      STEMI patients with greater residual thrombus burden after aspiration
      thrombectomy had worse microvascular dysfunction and greater myocardial damage
      compared with those with smaller residual thrombus burden.

PMID- 27712736
TI  - Aspiration Thrombectomy: The Possible Importance of Effective Thrombus Removal
      and Minimal Residual Thrombus Burden.

PMID- 27712737
TI  - Safety and Efficacy of a Pharmacoinvasive Strategy in ST-Segment Elevation
      Myocardial Infarction: A Patient Population Study Comparing a Pharmacoinvasive
      Strategy With a Primary Percutaneous Coronary Intervention Strategy Within a
      Regional System.
AB  - OBJECTIVES: This study investigated the safety and efficacy of a pharmacoinvasive
      strategy compared with a primary percutaneous coronary intervention (PCI)
      strategy for ST-segment elevation myocardial infarction (STEMI) in the context of
      a real-world system. BACKGROUND: Primary PCI continues to be the optimal
      reperfusion therapy; however, in areas where PCI centers are not readily
      available, a pharmacoinvasive strategy has been proposed. METHODS: The University
      of Ottawa Heart Institute regional STEMI system provides a primary PCI strategy
      for patients presenting within a 90-km radius from the PCI center, and a
      pharmacoinvasive strategy for patients outside this limit. We included all
      confirmed STEMI patients between April 2009 and May 2011. The primary efficacy
      outcome was a composite of mortality, reinfarction, or stroke and the primary
      safety outcome was major bleeding. RESULTS: We identified 236 and 980 consecutive
      patients enrolled in pharmacoinvasive and primary PCI strategies, respectively.
      The median door-to-needle time was 31 min in the pharmacoinvasive group and the
      median door-to-balloon time was 95 min in the primary PCI group. In a
      multivariable model, there was no significant difference in the primary efficacy
      outcome (odds ratio: 1.54; p = 0.21); however, the propensity for more bleeding
      with a pharmacoinvasive strategy approached statistical significance (odds ratio:
      2.02; p = 0.08). CONCLUSIONS: Within the context of a STEMI system, a
      pharmacoinvasive strategy was associated with similar rates of the composite of
      mortality, reinfarction, or stroke as compared with a primary PCI strategy;
      however, there was a propensity for more bleeding with a pharmacoinvasive
      strategy.

PMID- 27712738
TI  - The Choice Is Reperfusion Therapy: But Which One?

PMID- 27712740
TI  - Computing Fractional Flow Reserve During Coronary Angiography: How Good Is Good
      Enough?

PMID- 27712739
TI  - Diagnostic Accuracy of Fast Computational Approaches to Derive Fractional Flow
      Reserve From Diagnostic Coronary Angiography: The International Multicenter FAVOR
      Pilot Study.
AB  - OBJECTIVES: The aim of this prospective multicenter study was to identify the
      optimal approach for simple and fast fractional flow reserve (FFR) computation
      from radiographic coronary angiography, called quantitative flow ratio (QFR).
      BACKGROUND: A novel, rapid computation of QFR pullbacks from 3-dimensional
      quantitative coronary angiography was developed recently. METHODS: QFR was
      derived from 3 flow models with: 1) fixed empiric hyperemic flow velocity (fixed
      flow QFR [fQFR]); 2) modeled hyperemic flow velocity derived from angiography
      without drug-induced hyperemia (contrast-flow QFR [cQFR]); and 3) measured
      hyperemic flow velocity derived from angiography during adenosine-induced
      hyperemia (adenosine-flow QFR [aQFR]). Pressure wire-derived FFR, measured during
      maximal hyperemia, served as the reference. Separate independent core
      laboratories analyzed angiographic images and pressure tracings from 8 centers in
      7 countries. RESULTS: The QFR and FFR from 84 vessels in 73 patients with
      intermediate coronary lesions were compared. Mean angiographic percent diameter
      stenosis (DS%) was 46.1 +/- 8.9%; 27 vessels (32%) had FFR <= 0.80. Good
      agreement with FFR was observed for fQFR, cQFR, and aQFR, with mean differences
      of 0.003 +/- 0.068 (p = 0.66), 0.001 +/- 0.059 (p = 0.90), and -0.001 +/- 0.065
      (p = 0.90), respectively. The overall diagnostic accuracy for identifying an FFR
      of <=0.80 was 80% (95% confidence interval [CI]: 71% to 89%), 86% (95% CI: 78% to
      93%), and 87% (95% CI: 80% to 94%). The area under the receiver-operating
      characteristic curve was higher for cQFR than fQFR (difference: 0.04; 95% CI:
      0.01 to 0.08; p < 0.01), but did not differ significantly between cQFR and aQFR
      (difference: 0.01; 95% CI: -0.04 to 0.06; p = 0.65). Compared with DS%, both cQFR
      and aQFR increased the area under the receiver-operating characteristic curve by
      0.20 (p < 0.01) and 0.19 (p < 0.01). The positive likelihood ratio was 4.8, 8.4,
      and 8.9 for fQFR, cQFR, and aQFR, with negative likelihood ratio of 0.4, 0.3, and
      0.2, respectively. CONCLUSIONS: The QFR computation improved the diagnostic
      accuracy of 3-dimensional quantitative coronary angiography-based identification
      of stenosis significance. The favorable results of cQFR that does not require
      pharmacologic hyperemia induction bears the potential of a wider adoption of FFR
      based lesion assessment through a reduction in procedure time, risk, and costs.

PMID- 27712742
TI  - Percutaneous Mitral Repair: A Potential "Standard" for Functional Mitral
      Regurgitation?

PMID- 27712743
TI  - Aggressive Post-Dilation of Coronary Stents and Restenosis.

PMID- 27712741
TI  - Transcatheter Mitral Annuloplasty in Chronic Functional Mitral Regurgitation: 6
      Month Results With the Cardioband Percutaneous Mitral Repair System.
AB  - OBJECTIVES: This study sought to show safety and efficacy of the Cardioband
      system during 6 months after treatment. BACKGROUND: Current surgical and medical
      treatment options for functional mitral regurgitation (FMR) are limited. The
      Cardioband system (Valtech Cardio, OrYehuda, Israel) is a novel transvenous,
      transseptal direct annuloplasty device. METHODS: Thirty-one patients (71.8 +/-
      6.9 years of age; 83.9% male; EuroSCORE II: 8.6 +/- 5.9) with moderate to severe
      FMR, symptomatic heart failure, and depressed left ventricular function (left
      ventricular ejection fraction 34 +/- 11%) were prospectively enrolled. RESULTS:
      Procedural success rate, defined as delivery of the entire device, was 100%.
      There were no periprocedural deaths (0%), and mortality rate at 1 month or prior
      to hospital discharge and at 7 months was 5% and 9.7% respectively. Cinching of
      the implanted Cardioband reduced the annular septolateral dimension by >30% from
      3.7 +/- 0.5 cm at baseline to 2.5 +/- 0.4 cm after 1 month and to 2.4 +/- 0.4 cm
      after 6 months, respectively (p < 0.001). Percentage of patients with FMR >=3 was
      reduced from 77.4% to 10.7% 1 month after the procedure (p < 0.001) and 13.6% (p
      < 0.001) at 7 months. Percentage of patients with New York Heart Association
      functional class III/IV decreased from 95.5% to 18.2% after 7 months (p < 0.001);
      exercise capacity as assessed by 6-min walking test increased from 250 +/- 107 m
      to 332 +/- 118 m (p < 0.001) and quality of life (Minnesota Living With Heart
      Failure Questionnaire) was also significantly improved (p < 0.001). CONCLUSIONS:
      In this feasibility trial in symptomatic patients with FMR, transcatheter mitral
      annuloplasty with the Cardioband was effective in reducing MR and was associated
      with improvement in heart failure symptoms and demonstrated a favorable safety
      profile. (Cardioband With Transfemoral Delivery System; NCT01841554).

PMID- 27712744
TI  - Reply: Aggressive Post-Dilation of Coronary Stents and Restenosis.

PMID- 27712745
TI  - A Year to Learn It All: A Call-to-Action for a Comprehensive, Yet Not Longer,
      Training of the Next Generation of Interventional Cardiologists.

PMID- 27712746
TI  - Setting the Goals in the Management of Mutilated Injuries of the Hand-Impressions
      Based on the Ganga Hospital Experience.
AB  - Mutilated injuries need to be treated aggressively and appropriately to avoid
      amputation or severe disability in the individual. Assessment of the management
      of these injuries on a global level reveals that there is a gap between the need
      and availability of the skilled manpower to manage these injuries. There is also
      a gap in the utilization of the available services. These gaps need to be covered
      or narrowed as far as possible. Although some measures need policy changes and
      improvement of health care delivery infrastructure, simpler measures taken at the
      final health care delivery level can significantly improve the final outcome.

PMID- 27712747
TI  - The Biomechanical Impact of Digital Loss and Fusion Following Trauma: Setting the
      Patient up for Success.
AB  - Surgeons managing mutilating hand injures are faced with difficult decisions
      between attempting to salvage remaining or injured digits or proceeding to
      amputation and fusion. Through application of a basic understanding of hand
      biomechanics, the surgeon may more accurately predict what motion and function
      can best be salvaged. This article provides an explanation of how amputation,
      fusion, and tendon loss can affect postoperative hand motion. The surgeon can use
      these concepts in planning the reconstruction or preparing the foundation for
      secondary reconstructive procedures to achieve the highest functional outcome for
      the patient.

PMID- 27712749
TI  - Mutilating Hand Injuries in Children.
AB  - Mutilating hand injuries in children are injuries that are significant not only
      because of the actual injury caused to tissue but also owing to the significant
      psychological impact they have on the patient and family alike. Management of
      these injuries requires significant surgical skill as well as a well-planned and
      well-executed treatment protocol. This article discusses the etiology, incidence
      as well as treatment of mutilating hand injuries in a child. Relevant literature
      has been reviewed and appropriate treatment guidelines have been provided.

PMID- 27712748
TI  - Measuring Functional and Patient-Reported Outcomes After Treatment of Mutilating
      Hand Injuries: A Global Health Approach.
AB  - Understanding the global burden of trauma, particularly upper extremity trauma,
      is necessary in addressing the need for surgical services. Critical to that
      mission is to understand, and accurately measure, disability and related
      disability-adjusted life-years from massive upper extremity trauma. The impact of
      these injuries is magnified when considering that they frequently occur to young
      people in prime working years. This article discusses these social and medical
      system issues and reviews components of a comprehensive approach to measuring
      outcomes after these injuries. Patient-reported outcomes are highlighted. Methods
      of optimizing outcomes measurements and studies, disability assessments, and
      associated research are also discussed.

PMID- 27712750
TI  - Skin Coverage Considerations in a Mutilating Hand Injury.
AB  - The foremost goal of managing a mutilated hand is provision of adequate skin
      coverage. The most suitable method is free tissue transfer. The specific role of
      volar surface requires replacement tissue to have similar texture for
      aesthetically satisfactory and functionally acceptable outcomes. Hand surgeons
      must approach mutilating hand injuries with the recognition that no 2 injuries
      are ever the same. The injured hand must be evaluated on the individual demand
      and characteristics of hand use. Optimal function and aesthetic outcomes require
      appropriate selection of skin coverage. Lost tissues must be replaced like with
      like tissue.

PMID- 27712751
TI  - Skeletal Fixation in a Mutilated Hand.
AB  - Hand fracture fixation in mutilating injuries is characterized by multiple
      challenges due to possible skeletal disorganization and concomitant severe injury
      of soft tissue structures. The effects of skeletal disruption are best analyzed
      as divided into specific locales in the hand: radial, ulnar, proximal, and
      distal. Functional consequences of injuries in each of these regions are
      discussed. Although a variety of implants are now in vogue, K-wire fixation has
      stood the test of time and is especially useful in multiple fracture situations.
      Segmental bone loss is quite common in such injuries, which can be safely
      reconstructed in a staged manner.

PMID- 27712752
TI  - Primary Thumb Reconstruction in a Mutilated Hand.
AB  - The thumb should be preserved at all costs, and major efforts to preserve it are
      justified. If nothing can be done (or desperate measures fail), classic
      procedures or a toe-to-hand are indicated. This article will not only discuss
      some tips to succeed in extreme acute scenarios, but will also consider the
      indications of other alternatives in the acute or subacute setting.

PMID- 27712753
TI  - Secondary Thumb Reconstruction in a Mutilated Hand.
AB  - The thumb plays an integral role in hand function. Traumatic amputation results
      in significant morbidity. With loss of the thumb, up to a 40% reduction in hand
      function may result. Thumb replantation must be attempted when possible. The
      goals of thumb reconstruction are to replicate normal function as closely as
      possible, minimize donor site morbidity, and expedite recovery. In the setting of
      a mutilated hand, the status of the remaining digits must be carefully assessed.
      Toe transfers, osteoplastic thumb reconstruction, and pollicization are commonly
      used. This article summarizes the indications and technical considerations in
      addressing the deficiencies after thumb amputation.

PMID- 27712754
TI  - Metacarpal-Like and Metacarpal Hand.
AB  - The metacarpal-like and metacarpal hand injuries are devastating conditions that
      render the hand nonfunctional. Although the metacarpal hand is well-studied, the
      metacarpal-like hand is never addressed. The authors, using the same principles
      as in the classification and treatment of metacarpal hand, propose an easy to
      follow treatment algorithm for metacarpal-like hand injury to guide the
      reconstructive surgeon. For both injuries, microsurgical toe-to-hand
      transplantation can restore an acceptable level of function if done properly.
      Meticulous planning is essential for the toe-to-hand surgery to achieve its prime
      goal of stable tripod pinch with insignificant morbidity at the donor sites.

PMID- 27712755
TI  - Secondary Interventions for Mutilating Hand Injuries.
AB  - Care of the reconstructed hand following mutilating injury is akin to the care of
      a vintage car. Its mechanisms are delicate, spare parts are limited, touch-ups
      are required often, and a major overhaul is indicated rarely. Secondary
      interventions are indicated for completion of staged primary procedures,
      management of complications, targeted improvement of function, and enhancement of
      appearance of the reconstructed hand. The approach to secondary reconstruction
      depends on the patient's age, and vocational and recreational requirements. It is
      also influenced by the constant evolution of surgeons' reconstructive philosophy,
      experience, and technology.

PMID- 27712756
TI  - Challenges Posed by Delayed Presentation of Mutilating Hand Injuries.
AB  - Management of mutilating hand injury is a challenge for any hand surgeon. Delay
      in presentation makes management even more challenging, usually because of
      inadequate initial assessment, inadequate debridement leading to infection, and
      secondary loss of tissues from exposure and desiccation. The aim is to obtain a
      functional hand by radical debridement, adequate assessment of the injury,
      appropriately timed reconstruction, and physiotherapy and rehabilitation. The
      hand surgeon must pay attention to the appearance of the hand by elimination of
      deformities, unsightly scars and bulky flaps to help to restore confidence in the
      patient to face the demands of daily living.

PMID- 27712757
TI  - Pushing the Boundaries of Salvage in Mutilating Upper Limb Injuries: Techniques
      in Difficult Situations.
AB  - With the available microsurgical techniques, salvage of the limb can almost
      always provide a useful upper limb, even in the most complex combined injuries.
      Having a low threshold for revascularization of doubtfully viable extremities and
      making full use of the current armamentarium of soft tissue cover techniques,
      including flow through free flaps, will salvage many limbs. Secondary procedures,
      including free functioning muscle transfers and toe transfers, further increase
      the possible functional outcome. Even in the most complex combined injuries,
      intelligent reconstruction will obtain better outcomes than the best available
      prosthesis, making the efforts of salvage worthwhile.

PMID- 27712758
TI  - Reconstructing Lives.

PMID- 27712759
TI  - An Overview of Nonsteroidal Antiinflammatory Drug Reactions.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, are among the
      most commonly used drugs worldwide. They account for a large number of adverse
      drug reactions (ADRs). The prevalence of NSAID-induced reactions is increasing.
      Distinguishing between a predicted side effect of a drug and a potentially life
      threatening hypersensitivity reaction is essential to manage the affected
      patient. However, most clinicians find it difficult to diagnose these types of
      reactions despite published classification schemes. In this overview, we provide
      an in-depth review of NSAID classification, types of NSAID reactions, diagnostic
      tactics, and management strategies to provide the reader with a greater
      understanding of NSAID-induced reactions.

PMID- 27712760
TI  - Clinical Characteristics of Aspirin-Exacerbated Respiratory Disease.
AB  - Aspirin-exacerbated respiratory disease is a significant endotype of both asthma
      and chronic rhinosinusitis with nasal polyps. The disease demonstrates what seems
      to be a unified inflammatory mechanism culminating in highly eosinophilic nasal
      polyp disease and asthma. The rate of polyp recurrence and morbidity from asthma
      exacerbations are significant and warrant separating this group diagnostically
      from aspirin-tolerant peers. Given the unique anti-inflammatory effects of
      aspirin and the evolving landscape of new, targeted biologic treatments, it is
      even more incumbent to consider this diagnosis and offer patients treatment
      specific for the disease.

PMID- 27712761
TI  - Diagnostic Evaluation in Aspirin-Exacerbated Respiratory Disease.
AB  - Aspirin-exacerbated respiratory disease (AERD) is a distinct clinical condition
      characterized by chronic sinusitis with nasal polyps, asthma, and
      hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs).
      Distinguishing AERD from other forms of chronic sinusitis, asthma, and NSAID
      reactivity has important clinical implications for management. The clinical
      history is helpful, but not adequate for confirming the diagnosis of AERD, in
      most cases. Diagnostic provocation challenge remains the only way to confirm or
      exclude the diagnosis of AERD. This article discusses the utility of the clinical
      history and the current evidence regarding measures that optimize the safety of
      performing diagnostic NSAID provocation challenges.

PMID- 27712762
TI  - Aspirin-Exacerbated Respiratory Disease as an Endotype of Chronic Rhinosinusitis.
AB  - Aspirin-Exacerbated Respiratory Disease (AERD) and Chronic Rhinosinusitis with
      Nasal Polyps (CRSwNP) are both characterized by the presence of chronic sinonasal
      inflammation and nasal polyps. Unlike in CRSwNP, AERD patients develop
      respiratory reactions following ingestion of COX-1 inhibitors. AERD patients
      also, on average, have worse upper respiratory disease with increased sinonasal
      symptoms, mucosal inflammation and requirements for revision sinus surgery when
      compared to CRSwNP patients. While no single genetic factor has been identified
      in either CRSwNP or AERD to date, differences in the metabolism of arachidonic
      acid as well as innate immune cell activation may uniquely contribute to AERD
      pathogenesis.

PMID- 27712763
TI  - Pathogenesis of Aspirin-Induced Reactions in Aspirin-Exacerbated Respiratory
      Disease.
AB  - The acute clinical symptoms that develop following the oral ingestion of aspirin,
      or any other inhibitor of cyclooxygenase-1, are well established in aspirin
      exacerbated respiratory disease: nasal congestion, rhinorrhea, and bronchospasm.
      Less commonly, gastrointestinal distress, rash, angioedema, or urticaria also
      develops. However, the pathobiology that drives these clinical reactions is
      poorly understood. Use of an intranasal aspirin challenge protocol or
      administration of premedications inhibiting the leukotriene pathway decreases the
      severity of clinical reaction, which suggests the involvement of both local
      effector cells and cysteinyl leukotrienes in the pathogenesis of aspirin-induced
      reactions.

PMID- 27712764
TI  - Performing Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease.
AB  - Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic
      rhinosinusitis with nasal polyps, asthma, and reactions to cyclooxygenase-1
      inhibiting drugs. This condition is often refractory to standard medical
      treatments and results in aggressive nasal polyposis that often requires multiple
      sinus surgeries. Aspirin desensitization followed by daily aspirin therapy is an
      important treatment option, and its efficacy has been validated in multiple
      research studies. Aspirin desensitization is not without risk, but specific
      protocols and recommendations exist to mitigate the risk. Most patients with AERD
      can undergo aspirin desensitization in an outpatient setting under the
      supervision of an allergist.

PMID- 27712765
TI  - Clinical Trials of Aspirin Treatment After Desensitization in Aspirin-Exacerbated
      Respiratory Disease.
AB  - The clinical efficacy of aspirin treatment after desensitization in patients with
      respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs has been
      documented in observational studies and in double-blind placebo-controlled
      trials. There is no general agreement with regard to the optimal maintenance dose
      or duration of treatment with acetylsalicylic acid after desensitization, thus
      further studies are necessary to offer clear guidelines to clinicians. This
      article summarizes data from noncontrolled, active-control, and placebo
      controlled trials assessing clinical effectiveness and reporting on safety of
      treatment with acetylsalicylic acid in desensitized patients with respiratory
      disease exacerbated by nonsteroidal anti-inflammatory drugs.

PMID- 27712767
TI  - Mechanisms of Benefit with Aspirin Therapy in Aspirin-Exacerbated Respiratory
      Disease.
AB  - Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome
      characterized by severe persistent asthma, hyperplastic eosinophilic sinusitis
      with nasal polyps, and an intolerance to aspirin and other NSAIDs that
      preferentially inhibit COX-1. For more than 30 years, aspirin desensitization has
      proven to be of significant long-term benefit in carefully selected patients with
      AERD. Despite this, the exact mechanisms behind the therapeutic effects of
      aspirin desensitization remain poorly understood. In this article, we review the
      current understanding of the mechanisms of aspirin desensitization and discuss
      future areas of investigation.

PMID- 27712766
TI  - Eosinophils and Mast Cells in Aspirin-Exacerbated Respiratory Disease.
AB  - Aspirin-exacerbated respiratory disease (AERD) involves overexpression of
      proinflammatory mediators, including 5-lipoxygenase and leukotriene C4 synthase
      (LTC4S), resulting in constitutive overproduction of cysteinyl leukotrienes. Mast
      cells and eosinophils have roles in mediating many of the observed effects.
      Increased levels of both interleukin-4 (IL-4) and interferon (IFN)-gamma are
      present in the tissue of patients with AERD. Previous studies showed that IL-4 is
      primarily responsible for the upregulation of LTC4S by mast cells. Our studies
      show that IFN-gamma, but not IL-4, drives this process in eosinophils. This
      article examines the overall role that eosinophils and mast cells contribute to
      the pathophysiology of AERD.

PMID- 27712768
TI  - Lipid Mediators in Aspirin-Exacerbated Respiratory Disease.
AB  - Aspirin-exacerbated respiratory disease (AERD) is a syndrome of severe asthma and
      rhinosinusitis with nasal polyposis with exacerbations of baseline eosinophil
      driven and mast cell-driven inflammation after nonsteroidal antiinflammatory drug
      ingestion. Although the underlying pathophysiology is poorly understood,
      dysregulation of the cyclooxygenase and 5-lipoxygenase pathways of arachidonic
      acid metabolism is thought to be key. Central features of AERD pathogenesis are
      overproduction of proinflammatory and bronchoconstrictor cysteinyl leukotrienes
      and prostaglandin (PG) D2 and inhibition of bronchoprotective and
      antiinflammatory PGE2. Imbalance in the ratio of these lipid mediators likely
      leads to the increased eosinophilic and mast cell inflammatory responses in the
      respiratory tract.

PMID- 27712770
TI  - From "Samter's Triad" to "NERD": The Long and Winding Road to Understanding
      Aspirin-Exacerbated Respiratory Disease.

PMID- 27712771
TI  - Aspirin-Exacerbated Respiratory Disease: The Hunt for the "Rosetta Stone" of
      Respiratory Inflammation.

PMID- 27712769
TI  - Genetic and Epigenetic Components of Aspirin-Exacerbated Respiratory Disease.
AB  - Aspirin-exacerbated respiratory disease (AERD) severity and its clinical
      phenotypes are characterized by genetic variation within pathways for arachidonic
      acid metabolism, inflammation, and immune responses. Epigenetic effects,
      including DNA methylation and histone protein modification, contribute to
      regulation of many genes that contribute to inflammatory states in AERD. The
      development of noninvasive, predictive clinical tests using data from genetic,
      epigenetic, pharmacogenetic, and biomarker studies will improve precision
      medicine efforts for AERD and asthma treatment.

PMID- 27712773
TI  - How Robust Is the Evidence for Recommending Very Low Salt Intake in Entire
      Populations?

PMID- 27712772
TI  - Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension
      Prevention.
AB  - BACKGROUND: The relationship between lower sodium intake and total mortality
      remains controversial. OBJECTIVES: This study examined the relationship between
      well-characterized measures of sodium intake estimated from urinary sodium
      excretion and long-term mortality. METHODS: Two trials, phase I (1987 to 1990),
      over 18 months, and phase II (1990 to 1995), over 36 months, were undertaken in
      TOHP (Trials of Hypertension Prevention), which implemented sodium reduction
      interventions. The studies included multiple 24-h urine samples collected from
      pre-hypertensive adults 30 to 54 years of age during the trials. Post-trial
      deaths were ascertained over a median 24 years, using the National Death Index.
      The associations between mortality and the randomized interventions as well as
      with average sodium intake were examined. RESULTS: Among 744 phase I and 2,382
      phase II participants randomized to sodium reduction or control, 251 deaths
      occurred, representing a nonsignificant 15% lower risk in the active intervention
      (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.66 to 1.09; p = 0.19).
      Among 2,974 participants not assigned to an active sodium intervention, 272
      deaths occurred. There was a direct linear association between average sodium
      intake and mortality, with an HR of 0.75, 0.95, and 1.00 (references) and 1.07 (p
      trend = 0.30) for <2,300, 2,300 to <3,600, 3,600 to <4,800, and >=4,800 mg/24 h,
      respectively; and with an HR of 1.12 per 1,000 mg/24 h (95% CI: 1.00 to 1.26; p =
      0.05). There was no evidence of a J-shaped or nonlinear relationship. The HR per
      unit increase in sodium/potassium ratio was 1.13 (95% CI: 1.01 to 1.27; p =
      0.04). CONCLUSIONS: We found an increased risk of mortality for high-sodium
      intake and a direct relationship with total mortality, even at the lowest levels
      of sodium intake. These results are consistent with a benefit of reduced sodium
      and sodium/potassium intake on total mortality over a 20-year period.

PMID- 27712775
TI  - Who Should Undergo Chronic Total Occlusion Percutaneous Coronary Intervention?:
      The EXPLORation Continues.

PMID- 27712774
TI  - Percutaneous Intervention for Concurrent Chronic Total Occlusions in Patients
      With STEMI: The EXPLORE Trial.
AB  - BACKGROUND: In 10% to 15% of patients with ST-segment elevation myocardial
      infarction (STEMI), concurrent coronary chronic total occlusion (CTO) in a non
      infarct-related artery is present and is associated with increased morbidity and
      mortality. OBJECTIVES: The EXPLORE (Evaluating Xience and Left Ventricular
      Function in Percutaneous Coronary Intervention on Occlusions After ST-Elevation
      Myocardial Infarction) trial evaluated whether patients with STEMI and concurrent
      CTO in a non-infarct-related artery benefit from additional percutaneous coronary
      intervention (PCI) of CTO shortly after primary PCI. METHODS: From November 2007
      through April 2015, we enrolled 304 patients with acute STEMI who underwent
      primary PCI and had concurrent CTO in 14 centers in Europe and Canada. A total of
      150 patients were randomly assigned to early PCI of the CTO (CTO PCI), and 154
      patients were assigned to conservative treatment without PCI of the CTO (no CTO
      PCI). Primary outcomes were left ventricular ejection fraction (LVEF) and left
      ventricular end diastolic volume (LVEDV) on cardiac magnetic resonance imaging
      after 4 months. RESULTS: The investigator-reported procedural success rate in the
      CTO PCI arm of the trial was 77%, and the adjudicated success rate was 73%. At 4
      months, mean LVEF did not differ between the 2 groups (44.1 +/- 12.2% vs. 44.8 +/
      11.9%, respectively; p = 0.60). Mean LVEDV at 4 months was 215.6 +/- 62.5 ml in
      the CTO PCI arm versus 212.8 +/- 60.3 ml in the no-CTO PCI arm (p = 0.70).
      Subgroup analysis revealed that patients with CTO located in the left anterior
      descending coronary artery who were randomized to the CTO PCI strategy had
      significantly higher LVEF compared with patients randomized to the no-CTO PCI
      strategy (47.2 +/- 12.3% vs. 40.4 +/- 11.9%; p = 0.02). There were no differences
      in terms of 4-month major adverse coronary events (5.4% vs. 2.6%; p = 0.25).
      CONCLUSIONS: Additional CTO PCI within 1 week after primary PCI for STEMI was
      feasible and safe. In patients with STEMI and concurrent CTO, we did not find an
      overall benefit for CTO PCI in terms of LVEF or LVEDV. The finding that early CTO
      PCI in the left anterior descending coronary artery subgroup was beneficial
      warrants further investigation. (Evaluating Xience and Left Ventricular Function
      in Percutaneous Coronary Intervention on Occlusions After ST-Segment Elevation
      Myocardial Infarction; NTR1108).

PMID- 27712777
TI  - TAVR Prognosis, Aging, and the Second TAVR Tsunami: Insights From France.

PMID- 27712779
TI  - Cardiac-Coronary Coupling.

PMID- 27712778
TI  - Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy: Insights From
      Wave Intensity Analysis and Magnetic Resonance.
AB  - BACKGROUND: Angina is common in hypertrophic cardiomyopathy (HCM) and is
      associated with abnormal myocardial perfusion. Wave intensity analysis improves
      the understanding of the mechanics of myocardial ischemia. OBJECTIVES: Wave
      intensity analysis was used to describe the mechanisms underlying perfusion
      abnormalities in patients with HCM. METHODS: Simultaneous pressure and flow were
      measured in the proximal left anterior descending artery in 33 patients with HCM
      and 20 control patients at rest and during hyperemia, allowing calculation of
      wave intensity. Patients also underwent quantitative first-pass perfusion cardiac
      magnetic resonance to measure myocardial perfusion reserve. RESULTS: Patients
      with HCM had a lower coronary flow reserve than control subjects (1.9 +/- 0.8 vs.
      2.7 +/- 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very
      large backward compression wave during systole (38 +/- 11% vs. 21 +/- 6%; p <
      0.001) and a proportionately smaller backward expansion wave (27% +/- 8% vs. 33
      +/- 6%; p = 0.006) compared with control subjects. Patients with severe left
      ventricular outflow tract obstruction had a bisferiens pressure waveform
      resulting in an additional proximally originating deceleration wave during
      systole. The proportion of waves acting to accelerate coronary flow increased
      with hyperemia, and the magnitude of change was proportional to the myocardial
      perfusion reserve (rho = 0.53; p < 0.01). CONCLUSIONS: Coronary flow in patients
      with HCM is deranged. Distally, compressive deformation of intramyocardial blood
      vessels during systole results in an abnormally large backward compression wave,
      whereas proximally, severe left ventricular outflow tract obstruction is
      associated with an additional deceleration wave. Perfusion abnormalities in HCM
      are not simply a consequence of supply/demand mismatch or remodeling of the
      intramyocardial blood vessels; they represent a dynamic interaction with the
      mechanics of myocardial ischemia that may be amenable to treatment.

PMID- 27712780
TI  - Carbamylated Low-Density Lipoproteins Induce a Prothrombotic State Via LOX-1:
      Impact on Arterial Thrombus Formation In Vivo.
AB  - BACKGROUND: Carbamylation alters low-density lipoprotein (LDL) structure and is
      thought to promote vascular inflammation and dysfunction in patients with chronic
      kidney disease (CKD). OBJECTIVES: This study sought to determine whether
      carbamylated LDL (cLDL) exerts prothrombotic effects in vascular cells and
      platelets and whether cLDL enhances arterial thrombus formation in vivo. METHODS:
      LDL was isolated from healthy subjects or patients with CKD by sequential
      ultracentrifugation. Ex vivo carbamylation of LDL from healthy subjects was
      induced with potassium cyanate. Arterial thrombus formation was analyzed in a
      murine carotid artery photochemical injury model. Protein expression and mRNA
      levels were analyzed by Western blotting, flow cytometry, and real-time PCR.
      Platelet aggregation was measured by impedance aggregometry. RESULTS: Intravenous
      administration of cLDL in mice accelerated arterial thrombus formation compared
      to treatment with native LDL (nLDL) or vehicle. Tissue lysates of mouse carotid
      arteries revealed that cLDL induced the expression of TF, PAI-1, and LOX-1 mRNA
      in vascular cells. In human aortic smooth muscle and endothelial cells, cLDL
      induced TF and PAI-1 expression. In contrast, nLDL had no effect on either cell
      type. While nLDL and cLDL had no aggregatory effect on resting platelets, cLDL
      enhanced platelet aggregation in response to different agonists. This effect was
      mediated by mitogen-activated protein kinase p38 phosphorylation and LOX-1
      translocation to the surface. LDL isolated from patients with CKD mimicked the
      prothrombotic effects of cLDL on vascular cells, platelets, and thrombus
      formation in vivo. CONCLUSIONS: We found that cLDL induces prothrombotic effects
      in vascular cells and platelets by activation of the LOX-1 receptor and enhances
      thrombus formation in vivo. This observation reveals a new mechanism underlying
      the increased incidence of acute thrombotic events observed in patients with CKD
      and may lead to the development of new lipid-targeting therapies in this
      population.

PMID- 27712776
TI  - Late Outcomes of Transcatheter Aortic Valve Replacement in High-Risk Patients:
      The FRANCE-2 Registry.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) has revolutionized
      management of high-risk patients with severe aortic stenosis. However, survival
      and the incidence of severe complications have been assessed in relatively small
      populations and/or with limited follow-up. OBJECTIVES: This report details late
      clinical outcome and its determinants in the FRANCE-2 (FRench Aortic National
      CoreValve and Edwards) registry. METHODS: The FRANCE-2 registry prospectively
      included all TAVRs performed in France. Follow-up was scheduled at 30 days, at 6
      months, and annually from 1 to 5 years. Standardized VARC (Valve Academic
      Research Consortium) outcome definitions were used. RESULTS: A total of 4,201
      patients were enrolled between January 2010 and January 2012 in 34 centers.
      Approaches were transarterial (transfemoral 73%, transapical 18%, subclavian 6%,
      and transaortic or transcarotid 3%) or, in 18% of patients, transapical. Median
      follow-up was 3.8 years. Vital status was available for 97.2% of patients at 3
      years. The 3-year all-cause mortality was 42.0% and cardiovascular mortality was
      17.5%. In a multivariate model, predictors of 3-year all-cause mortality were
      male sex (p < 0.001), low body mass index, (p < 0.001), atrial fibrillation (p <
      0.001), dialysis (p < 0.001), New York Heart Association functional class III or
      IV (p < 0.001), higher logistic EuroSCORE (p < 0.001), transapical or subclavian
      approach (p < 0.001 for both vs. transfemoral approach), need for permanent
      pacemaker implantation (p = 0.02), and post-implant periprosthetic aortic
      regurgitation grade >=2 of 4 (p < 0.001). Severe events according to VARC
      criteria occurred mainly during the first month and subsequently in <2% of
      patients/year. Mean gradient, valve area, and residual aortic regurgitation were
      stable during follow-up. CONCLUSIONS: The FRANCE-2 registry represents the
      largest database available on late results of TAVR. Late mortality is largely
      related to noncardiac causes. Incidence rates of severe events are low after the
      first month. Valve performance remains stable over time.

PMID- 27712781
TI  - Carbamylated Low-Density Lipoprotein and Thrombotic Risk in Chronic Kidney
      Disease.

PMID- 27712785
TI  - Veterans Affairs Health Care System as Cardiology Training Site: A Fellow's
      Perspective.

PMID- 27712784
TI  - Preparing for a Value-Based Health Care System.

PMID- 27712782
TI  - The Supply and Demand of the Cardiovascular Workforce: Striking the Right
      Balance.
AB  - As the burden of cardiovascular disease in the United States continues to
      increase, uncertainty remains on how well-equipped the cardiovascular workforce
      is to meet the challenges that lie ahead. In a time when health care is rapidly
      shifting, numerous factors affect the supply and demand of the cardiovascular
      workforce. This Council Commentary critically examines several factors that
      influence the cardiovascular workforce. These include current workforce
      demographics and projections, evolving health care and practice environments, and
      the increasing burden of cardiovascular disease. Finally, we propose 3 strategies
      to optimize the workforce. These focus on cardiovascular disease prevention, the
      effective utilization of the cardiovascular care team, and alterations to the
      training pathway for cardiologists.

PMID- 27712783
TI  - Refining Statin Prescribing in Lower-Risk Individuals: Informing Risk/Benefit
      Decisions.
AB  - Guidelines from the American College of Cardiology/American Heart Association, as
      well as those from the Veterans Affairs/Department of Defense and the Joint
      British Societies all recommended treating more people with statins than previous
      guidelines. In each guideline, the decision-making process began with an
      assessment of overall cardiovascular risk. Each group proposed updated treatment
      thresholds, and all of them lowered the threshold compared with earlier
      guidelines. Since release of these new guidelines in 2013 and 2014, additional
      evidence has emerged to suggest a rationale for extending statin consideration to
      an even larger proportion of asymptomatic adults-even those with a 10-year
      atherosclerotic cardiovascular disease risk below 7.5%. This review discusses new
      findings since 2013 and proposes strategies emanating from the current guidelines
      to help clinicians and patients make more informed decisions about long-term
      statin use, especially pertinent to lower-risk patients.

PMID- 27712786
TI  - Transcatheter Aortic Valve Replacement to Treat Pure Aortic Regurgitation on
      Noncalcified Native Valves.

PMID- 27712787
TI  - Cardiac Fabry Disease With Late Gadolinium Enhancement Is a Chronic Inflammatory
      Cardiomyopathy.

PMID- 27712788
TI  - Takotsubo Cardiomyopathy Outcomes Should Be Stratified Based on the Triggering
      Etiology.

PMID- 27712789
TI  - Lipid Measurements: Fasting or Nonfasting, Women or Men.

PMID- 27712790
TI  - Reply: Lipid Measurements: Fasting or Nonfasting, Women or Men.

PMID- 27712791
TI  - Posterior Fossa Tumors in Adult Patients.
AB  - In adults, the most common expansile "mass" lesion in the posterior fossa is a
      subacute stroke, whereas the most common neoplastic lesion in the posterior fossa
      is cerebellar metastasis (intra-axial) or vestibular schwannoma (extra-axial).
      Those diseases fall outside the scope of this article, which focuses on primary
      intra-axial tumors of the posterior fossa in adults. This category of tumors is
      uncommon and more frequently encountered in children. This article reviews tumors
      of the cerebellum, brainstem, and fourth ventricle that are seen in adult
      patients, following categories from the 2007 World Health Organization
      classification of central nervous system tumors.

PMID- 27712792
TI  - Lymphomas-Part 1.
AB  - Primary central nervous system lymphomas are aggressive, high-cell-density
      tumors. There is recent increase in their incidence in immunocompetent patients.
      Knowledge of imaging findings on computed tomography and conventional MR imaging
      is important to suggest the diagnosis. Moreover, information obtained from
      advanced MR imaging techniques, such as diffusion-weighted imaging, diffusion
      tensor imaging, MR spectroscopy, perfusion-weighted imaging, and dynamic contrast
      enhanced studies, increases diagnostic confidence and helps distinguish them from
      other aggressive intracranial tumors. This article discusses typical imaging
      findings of primary and secondary central nervous system lymphomas on computed
      tomography and conventional MR imaging, advanced MR imaging techniques, and
      changes related to steroid therapy.

PMID- 27712793
TI  - Lymphomas-Part 2.
AB  - There are 2 types of central nervous system lymphoma: primary and secondary. Both
      have variable imaging features making them diagnostic challenges. Furthermore, a
      patient's immune status significantly alters the imaging findings. Familiarity
      with typical appearances, variations, and common mimics aids radiologists in
      appropriately considering lymphoma in the differential diagnosis. Moreover,
      special types of lymphoma, such as lymphomatosis cerebri, intravascular lymphoma,
      and lymphomatoid granulomatosis, also are found. This article discusses uncommon
      types of lymphoma and the differential diagnosis for focal, multifocal,
      meningeal, and infiltrative lymphomas.

PMID- 27712794
TI  - Pretreatment Evaluation of Glioma.
AB  - Glioma is considered the most common type of primary central nervous system (CNS)
      tumor. Imaging is crucial for diagnosis, characterization, grading, and
      therapeutic planning of CNS gliomas. Along with a brief description of
      conventional computed tomography and magnetic resonance imaging techniques, this
      article reviews the ever-developing role of modern imaging techniques in
      preoperative management of CNS gliomas. It discusses current clinical
      applications, promising features, and limitations of each imaging method.

PMID- 27712795
TI  - Posttreatment Evaluation of Brain Gliomas.
AB  - The imaging of treated gliomas is complicated by a variety of treatment related
      effects, which can falsely simulate disease improvement or progression.
      Distinguishing between disease progression and treatment effects is difficult
      with standard MR imaging pulse sequences and added specificity can be gained by
      the addition of advanced imaging techniques.

PMID- 27712796
TI  - Metastasis in Adult Brain Tumors.
AB  - Metastatic cancer to the central nervous system is primarily deposited by
      hematogenous spread in various anatomically distinct regions: calvarial,
      pachymeningeal, leptomeningeal, and brain parenchyma. A patient's overall
      clinical status and the information needed to make treatment decisions are the
      primary considerations in initial imaging modality selection. Contrast-enhanced
      MR imaging is the preferred imaging modality. Morphologic MR imaging is limited
      to delineating anatomic deraignment of tissues. Dynamic susceptibility contrast
      enhanced perfusion and diffusion-weighted physiology-based MR imaging sequences
      have been developed that complement morphologic MR imaging by providing
      additional diagnostic information.

PMID- 27712797
TI  - Extraparenchymal Lesions in Adults.
AB  - This article reviews the most frequent extra-axial tumors of the central nervous
      system, from the most common meningioma to some uncommon conditions, like Rosai
      Dorfman disease, focusing on imaging techniques, pearls, and pitfalls as well as
      a more practical approach.

PMID- 27712798
TI  - Advanced MR Imaging Techniques in Daily Practice.
AB  - This article presents a summary of advanced MR imaging techniques and their use
      in the evaluation of patients with brain tumors. It reviews diffusion-weighted
      imaging, diffusion-tensor imaging, T2* susceptibility-sensitive imaging, MR
      spectroscopy, MR perfusion, and functional MR imaging, and discusses their
      current roles in the evaluation of patients with brain tumors.

PMID- 27712799
TI  - Adult Brain Tumors and Pseudotumors: Interesting (Bizarre) Cases.
AB  - Some brain tumors results are interesting due to their rarity at presentation and
      overwhelming imaging characteristics, posing a diagnostic challenge in the eyes
      of any experienced neuroradiologist. This article focuses on the most important
      features regarding epidemiology, location, clinical presentation, histopathology,
      and imaging findings of cases considered "bizarre." A review of the most recent
      literature dealing with these unusual tumors and pseudotumors is presented,
      highlighting key points related to the diagnosis, treatments, outcomes, and
      differential diagnosis.

PMID- 27712800
TI  - Adult Brain Tumors.

PMID- 27712801
TI  - Adult Brain Tumors: Imaging Characterization of Primary, Secondary, and
      Extraparenchymal Tumors in the Central Nervous System, Including Findings on
      Advanced MR Imaging Techniques as well as Treatment-Related Abnormalities.

PMID- 27712802
TI  - A Second Set of Eyes: Pre-Patient Dismissal Interpretation.

PMID- 27712803
TI  - Doppler Echocardiographic Quantitation of Aortic Valve Stenosis: A Science in
      Constant Evolution.

PMID- 27712804
TI  - Quantitative Three-Dimensional Color Flow Echocardiography of Chronic Mitral
      Regurgitation: New Methods, New Perspectives, New Challenges.

PMID- 27712805
TI  - Learning to Permit Disruptive Innovation....

PMID- 27712806
TI  - ASE Governance Changes; ASEXIT not BREXIT.

PMID- 27712807
TI  - What Does the Restructure of the American Society of Echocardiography Board Mean
      for Sonographers?

PMID- 27712808
TI  - Innovations in Perioperative Cardiac Imaging.

PMID- 27712809
TI  - Genetic Evaluation for Craniofacial Conditions.
AB  - There are thousands of craniofacial disorders, each with a different etiology.
      All cases of orofacial clefts have an underlying genetic cause, ranging from
      multifactorial with an underlying genetic predisposition to chromosomal and
      single-gene etiologies. More than 50% of cases of Pierre Robin sequence are
      syndromic and 25% of craniosynostoses are syndromic. Clinical genetics evaluation
      is important for each patient with a craniofacial condition to make a proper
      diagnosis, counsel the family, and assist in management. This is an overview of
      the major components of the clinical genetics evaluation with a review of many
      syndromes associated with craniofacial disorders.

PMID- 27712810
TI  - Early Airway Intervention for Craniofacial Anomalies.
AB  - This article reviews the presentation of children with craniofacial anomalies by
      the most common sites of airway obstruction. Major craniofacial anomalies may be
      categorized into those with midface hypoplasia, mandible hypoplasia, combined
      midface and mandible hypoplasia, and midline deformities. Algorithms of airway
      interventions are provided to guide the initial management of these complex
      patients.

PMID- 27712811
TI  - Feeding Management in Infants with Craniofacial Anomalies.
AB  - The instinctual drive to gain nourishment can become complicated by structural
      differences, physiologic instability and environmental influences. Infants with
      craniofacial anomalies may experience significant feeding and swallowing
      difficulties related to the type and severity of the anomalies present as well as
      social-emotional interactions with caregivers. Typical outcome measures and
      feeding goals are discussed. Details regarding clinical and instrumental
      evaluation, including fiberoptic endoscopic evaluation of swallowing and modified
      barium swallow study, as well as management techniques are reported.

PMID- 27712812
TI  - Evaluation of Speech and Resonance for Children with Craniofacial Anomalies.
AB  - Children with craniofacial anomalies often demonstrate disorders of speech and/or
      resonance. Anomalies that affect speech and resonance are most commonly caused by
      clefts of the primary palate and secondary palate. This article discusses how
      speech-language pathologists evaluate the effects of dental and occlusal
      anomalies on speech production and the effects of velopharyngeal insufficiency on
      speech sound production and resonance. How to estimate the size of a
      velopharyngeal opening based on speech characteristics is illustrated. Nasometry,
      nasopharyngoscopy, and low-tech tools are discussed as adjunct methods to aid in
      the evaluation, treatment planning, and measurement of outcomes.

PMID- 27712813
TI  - Cleft Lip Repair, Nasoalveolar Molding, and Primary Cleft Rhinoplasty.
AB  - Cleft lip and palate are the fourth most common congenital birth defect.
      Management requires multidisciplinary care owing to the complexity of these
      clefts on midface growth, dentition, Eustachian tube function, and lip and nasal
      cosmesis. Repair requires planning, but can be performed systematically to reduce
      variability of outcomes. The use of primary rhinoplasty at the time of cleft lip
      repair can improve nose symmetry and reduce nasal deformity. Use of nasoalveolar
      molding ranging from lip taping to the use of preoperative infant orthopedics has
      played an important role in improving functional and cosmetic results of cleft
      lip repair.

PMID- 27712814
TI  - Cleft Palate Repair, Gingivoperiosteoplasty, and Alveolar Bone Grafting.
AB  - Repair of the cleft palate intends to establish the division between the oral and
      nasal cavity, thereby improving feeding, speech, and eustachian tube dysfunction
      all while minimizing the negative impact on maxillary growth. Before palate
      repair candidacy, timing and surgical method of repair is dependent on comorbid
      conditions, particularly cardiac disease, mandibular length, and palate width.
      Additionally, management of the alveolar cleft and the indications for
      gingivoperiosteoplasty versus secondary alveolar bone grafting is a controversial
      topic that weighs the risks and benefits of potentially sparing the patient an
      additional surgery against iatrogenic restriction of facial growth and
      malocclusion.

PMID- 27712815
TI  - Velopharyngeal Dysfunction Evaluation and Treatment.
AB  - Velopharyngeal dysfunction (VPD) can significantly impair a child's quality of
      life and may have lasting consequences if inadequately treated. This article
      reviews the work-up and management options for patients with VPD. An accurate
      perceptual speech analysis, nasometry, and nasal endoscopy are helpful to
      appropriately evaluate patients with VPD. Treatment options include nonsurgical
      management with speech therapy or a speech bulb and surgical approaches including
      double-opposing Z-plasty, sphincter pharyngoplasty, pharyngeal flap, or posterior
      wall augmentation.

PMID- 27712816
TI  - Intermediate and Definitive Cleft Rhinoplasty.
AB  - Intermediate and definitive cleft rhinoplasties are a challenging part of
      definitive cleft care. The anatomy of the cleft nose is severely affected by the
      structural deficits associated with congenital orofacial clefting. A
      comprehensive understanding of the related anatomy is crucial for understanding
      how to improve the appearance and function in patients with secondary cleft nasal
      deformities. Timing of intermediate and definitive rhinoplasty should be
      carefully considered. A thorough understanding of advanced rhinoplasty techniques
      is an important part of providing adequate care for patients with these
      deformities.

PMID- 27712818
TI  - Nonsyndromic Craniosynostosis and Deformational Head Shape Disorders.
AB  - This article provides an overview of etiology, epidemiology, pathology,
      diagnosis, and treatment of nonsyndromic craniosynostosis, including sagittal,
      metopic, coronal, lambdoid, and complex synostosis. Detailed discussion is
      presented regarding indications for surgical intervention and management options,
      including frontoorbital advancement, cranial vault reconstruction, endoscopic
      strip craniectomy, spring-assisted strip craniectomy, and cranial vault
      distraction osteogenesis. Deformational plagiocephaly is also presented with
      treatment options including repositioning, physical therapy, and helmet therapy.

PMID- 27712817
TI  - Craniofacial Microsomia.
AB  - Craniofacial microsomia (CFM) encompasses a broad spectrum of phenotypes. It is
      thought to result from defective development of the first and second pharyngeal
      arch structures, and generally presents with anomalies of the mandible and other
      facial bones, ears, and overlying soft tissues. The cause of CFM is thought to
      involve both extrinsic and genetic risk factors. Several classification systems
      have been developed to help stratify patients based on the severity of their
      defects. Treatment of patients includes repair of bony asymmetry as well as soft
      tissue defects and auricular anomalies. Surgical intervention is individualized
      based on each patient's deficits.

PMID- 27712819
TI  - Syndromic Craniosynostosis.
AB  - Syndromic craniosynostosis affects up to 1:30,000 live births with characteristic
      craniofacial growth restrictions, deformities, and other associated
      abnormalities, such as carpal-pedal anomalies and cognitive function impairment.
      More than 150 syndromes are associated with craniosynostosis. This article
      describes some commonalities and distinguishing features and management of
      syndromic synostosis. Also addressed is secondary synostosis, which is often
      found in syndromic children with problems related to microcephaly, hydrocephalus,
      or shunt-induced craniosynostosis, although pathophysiologically and genetically
      different. The importance of obtaining a thorough history and a complete physical
      and examination is highlighted. Adjuvant testing and multidisciplinary management
      are discussed.

PMID- 27712820
TI  - Tessier Clefts and Hypertelorism.
AB  - Tessier's classification system for rare craniofacial clefts remains the most
      widely used today. It denotes the position of the cleft process in a schema based
      around the orbit, and facilitates communication between surgeons regarding these
      complicated conditions. Tessier's classification is reviewed in detail, and a
      separate discussion of hypertelorism (increased distance between the bony orbits)
      follows, focusing on orbital hypertelorism in the setting of craniofacial clefts.

PMID- 27712822
TI  - Facial Nerve Rehabilitation.
AB  - Facial nerve paralysis, although uncommon in the pediatric population, occurs
      from several causes, including congenital deformities, infection, trauma, and
      neoplasms. Similar to the adult population, management of facial nerve disorders
      in children includes treatment for eye exposure, nasal obstruction/deviation,
      smile asymmetry, drooling, lack of labial function, and synkinesis. Free tissue
      transfer dynamic restoration is the preferred method for smile restoration in
      this population, with outcomes exceeding those of similar procedures in adults.

PMID- 27712821
TI  - Vascular Lesions.
AB  - Classification of vascular lesions based of off the biological behavior has
      greatly facilitated more accurate diagnoses, optimally defined treatment plans,
      and better outcomes. Treatment of vascular lesions has taken a more conservative
      surgical approach with reliance on select medical treatment options, which has
      greatly reduced morbidity and mortality resulting from extensive surgery. A
      multidisciplinary approach involving multiple surgical and pediatric
      subspecialties has led to advancement in both understanding and ideal treatment
      strategies of these lesions.

PMID- 27712823
TI  - Microtia Reconstruction.
AB  - Microtia reconstruction is a challenging endeavor that has seen significant
      technique evolution. It is important to educate patients and their families to
      determine the best hearing rehabilitation and ear reconstructive options.
      Microtia is often associated with aural atresia, hearing loss, and craniofacial
      syndromes. Optimal care is provided by multiple disciplines, including a
      reconstructive surgeon, an otologic surgeon, an audiologist, and a craniofacial
      pediatrician. Microtia management includes observation, prosthetic ear,
      autologous cartilage reconstruction, or alloplastic implant placement. Hearing
      management options are observation, bone conduction sound processor, or
      atresiaplasty with and without hearing aids. Appropriate counseling should be
      done to manage expectations.

PMID- 27712825
TI  - Craniomaxillofacial Trauma.
AB  - Facial trauma causes significant of morbidity in the United States. With injuries
      varying widely, the clinical benefits of antibiotics use in facial fracture
      treatment are not easily determined. The pediatric population is more predisposed
      to craniofacial trauma secondary to their increased cranial mass to body ratio.
      All patients with traumatic injury should be assessed according to the Advanced
      Trauma Life Support protocol. This article discusses the types and prevalence of
      injuries and approaches to management.

PMID- 27712824
TI  - The Evolution of Complex Microsurgical Midface Reconstruction: A Classification
      Scheme and Reconstructive Algorithm.
AB  - Orbito-malar reconstruction after oncological resection represents one of the
      most challenging facial reconstructive procedures. Until the last few decades,
      rehabilitation was typically prosthesis based with a limited role for surgery.
      The advent of microsurgical techniques allowed large-volume tissue reconstitution
      from a distant donor site, revolutionizing the potential approaches to these
      defects. The authors report a novel surgery-based algorithm and a classification
      scheme for complete midface reconstruction with a foundation in the Gillies
      principles of like-to-like reconstruction and with a significant role of computer
      aided virtual planning. With this approach, the authors have been able to achieve
      significantly better patient outcomes.

PMID- 27712826
TI  - Craniofacial Surgery for the Facial Plastic Surgeon.

PMID- 27712827
TI  - Are Filopodia Privileged Signaling Structures in Migrating Cells?
AB  - Filopodia are thin, fingerlike structures that contain bundled actin filaments
      and project from the cell periphery. These structures are dogmatically endowed
      with the ability to sense cues in the microenvironment, implying that filopodia
      foster local signal transduction, yet their small diameter hampers the imaging of
      dynamic processes therein. To overcome this challenge, we analyzed total internal
      reflection fluorescence images of migrating fibroblasts coexpressing either a
      plasma membrane marker or tagged AktPH domain, a translocation biosensor for
      signaling through the phosphoinositide 3-kinase pathway, along with a cytosolic
      volume marker. We devised a scheme to estimate the radii of filopodia using
      either the membrane marker or volume marker data, and we used that information to
      account for geometry effects in the biosensor data. With conservative estimates
      of relative target molecule abundance, it is revealed that filopodia typically
      harbor higher densities of 3' phosphoinositides than adjacent regions at the cell
      periphery. In this context at least, the analysis supports the filopodial
      signaling hypothesis.

PMID- 27712828
TI  - Sperm morphometry and chromatin condensation in Nelore bulls of different ages
      and their effects on IVF.
AB  - The aim of this study was to evaluate the chromatin packing and sperm head
      morphometry of cryopreserved semen of Nelore bulls (Bos taurus indicus) of
      different ages. Furthermore, the influence of the degree of chromatin compaction
      on in vitro embryo production (IVP) was investigated. Forty bulls were divided
      into three groups: young (1.8-2 years), adult (3.5-7 years), and senile (8-14.3
      years). The ejaculates were frozen according to standards established by the
      Artificial Insemination Center located in the Southeast of Brazil. Toluidine blue
      staining was used for simultaneous evaluation of the sperm chromatin and sperm
      head morphometry. Chromomycin A3 (CMA3) was applied to analyze sperm
      protamination and IVP for embryonic development. Spermatozoa of young bulls
      presented higher values for area (A, pixels), perimeter (P, pixels), and width
      (W, pixels) compared to adults and senile (young: A = 1848.5 +/- 119.79, P =
      10.23 +/- 0.29, and W = 1.95 +/- 0.1; adults: A = 1672.9 +/- 104.46, P = 9.86 +/-
      0.33, and W = 1.81 +/- 0.06; senile: A = 1723.1 +/- 124.41, P = 9.97 +/- 0.33,
      and W = 1.83 +/- 0.09; P < 0.0001) and showed higher protamination deficiency
      when analyzed by CMA3 (young: 1.57 +/- 0.76; adults: 1.09 +/- 0.63, and senile:
      0.90 +/- 0.59; P < 0.05). Likewise, variables of sperm head size (A, P, and W)
      and protamination assessed by CMA3 showed negative correlation with age and
      positive correlation with ellipticity, evaluated by toluidine blue method (P <
      0.05). Sperm head area was larger in spermatozoa presenting chromatin
      instabilities than spermatozoa without chromatin alteration (P < 0.0001). There
      was no difference in IVP when using semen with larger or smaller portions of
      spermatozoa with chromatin instabilities, indicating that the proportion of sperm
      with abnormal chromatin compaction (4%-16.15%) did not interfere with early
      embryonic development. From our results, it can be concluded that sperm of young
      Nelore bulls have larger heads compared to adults and senile due to reduced
      protamine content when evaluated by CMA3 and higher proportion of major sperm
      defects assessed by differential interference contrast microscopy.

PMID- 27712829
TI  - Thoracoabdominal aortic aneurysm repair: big case, big risk, big center!

PMID- 27712831
TI  - [The use of the G8 score for the patient of more than 75years old in digestive
      surgery for cancer].

PMID- 27712830
TI  - Parsing Heterogeneity in the Brain Connectivity of Depressed and Healthy Adults
      During Positive Mood.
AB  - BACKGROUND: There is well-known heterogeneity in affective mechanisms in
      depression that may extend to positive affect. We used data-driven parsing of
      neural connectivity to reveal subgroups present across depressed and healthy
      individuals during positive processing, informing targets for mechanistic
      intervention. METHODS: Ninety-two individuals (68 depressed patients, 24 never
      depressed control subjects) completed a sustained positive mood induction during
      functional magnetic resonance imaging. Directed functional connectivity paths
      within a depression-relevant network were characterized using Group Iterative
      Multiple Model Estimation (GIMME), a method shown to accurately recover the
      direction and presence of connectivity paths in individual participants. During
      model selection, individuals were clustered using community detection on neural
      connectivity estimates. Subgroups were externally tested across multiple levels
      of analysis. RESULTS: Two connectivity-based subgroups emerged: subgroup A,
      characterized by weaker connectivity overall, and subgroup B, exhibiting
      hyperconnectivity (relative to subgroup A), particularly among ventral affective
      regions. Subgroup predicted diagnostic status (subgroup B contained 81% of
      patients; 50% of control subjects; chi2 = 8.6, p = .003) and default mode network
      connectivity during a separate resting-state task. Among patients, subgroup B
      members had higher self-reported symptoms, lower sustained positive mood during
      the induction, and higher negative bias on a reaction-time task. Symptom-based
      depression subgroups did not predict these external variables. CONCLUSIONS:
      Neural connectivity-based categorization travels with diagnostic category and is
      clinically predictive, but not clinically deterministic. Both patients and
      control subjects showed heterogeneous, and overlapping, profiles. The larger and
      more severely affected patient subgroup was characterized by ventrally driven
      hyperconnectivity during positive processing. Data-driven parsing suggests
      heterogeneous substrates of depression and possible resilience in control
      subjects in spite of biological overlap.

PMID- 27712832
TI  - [Anti-PLD1 and anti-PD1 in advanced urothelial cancers: promises from early phase
      trials].

PMID- 27712833
TI  - [Acute cardiac disease in the Emergency Department: Fast-track approach for
      outpatient management].

PMID- 27712834
TI  - Diagnostic dilemma: Epstein-Barr virus (EBV) infectious mononucleosis with lung
      involvement or co-infection with Legionnaire's disease?
AB  - BACKGROUND: Hospitalized adults with fever and "pneumonia" can be a difficult
      diagnostic challenge particularly when the clinical findings may be due to
      different infectious diseases. METHODS: We recently had an elderly female who
      presented with fever, fatigue and dry cough with elevated serum transaminases and
      lung infiltrates. The diagnosis of Epstein-Barr virus (EBV) infectious
      mononucleosis (IM) was made based on a positive Monospot test, elevated EBV VCA
      IgM titer, and highly elevated EBV viral load. Her chest infiltrates were not
      accompanied by hilar adenopathy which may occur with EBV IM. Her dry cough
      persisted and she developed abdominal pain. RESULTS: Legionnaire's disease was
      considered because she had extra-pulmonary findings characteristic of
      Legionnaire's disease, e.g., relative bradycardia, abdominal pain, hyponatremia,
      hypophosphatemia, elevated ferritin levels, microscopic hematuria. Legionella
      titers were negative, but Legionella (serogroup 1) urinary antigen was positive.
      CONCLUSIONS: We present a diagnostic dilemma in an elderly female with both
      Legionnaire's disease and Epstein-Barr virus infectious mononucleosis with
      pulmonary involvement.

PMID- 27712836
TI  - Coronary calcification in familial hypercholesterolemia: Not all about LDL.

PMID- 27712835
TI  - Utility of 18 fludeoxyglucose in preoperative positon-emission tomography
      computed tomography (PET-CT) in the early diagnosis of exocrine pancreatic
      cancer: A study of 139 resected cases.
AB  - INTRODUCTION: In pancreatic ductal adenocarcinoma (PDA), surgical resection is
      the only curative treatment, but due to its late clinical presentation only 15
      25% patients are candidates for curative resection. The aim of this prospective,
      single-center study is to determine the diagnostic utility of preoperative PET-CT
      for early detection of PDA and early panIN lesions. METHODS: We studied the
      histopathological features of PDA and different panIN lesions in 139 surgical
      samples from patients undergoing pancreatic resection (from 2010-2014), comparing
      these results with preoperative PET-CT and MDCT study. For tumor diagnosis in PET
      CT maximum standard SUV 2.5 was used. Pancreatic baseline SUVmax is the maximum
      uptake of the radiotracer 18-2FDG on the ROI curve determined for the area of the
      normal pancreas after pathological reassessment with areas not affected by
      tumours or preneoplastic lesions. Tumour Uptake Index is the ratio between the
      tumour SUVmax and pancreatic baseline SUVmax. RESULTS: Using an standard maximum
      SUV value of 2.5, PET-CT sensitivity was 77.7% (108 of the 139 cases) against
      75.5% (105 of the 139 cases) of MDCT. But when we combined this value with
      maximum SUV of normal pancreatic tissue from each patient, PET-CT sensitivity
      improved its value to 94.9%. CONCLUSION: A combination of studies of PET-CT in
      tumor and non-tumor tissue of each patient might be a very useful diagnostic tool
      not only for preoperative diagnosis of PDA, but also for early panIN lesions.

PMID- 27712838
TI  - Quality of life in patients diagnosed with acute symptomatic pulmonary embolism.

PMID- 27712837
TI  - Influence of air pollution on exhaled carbon monoxide levels in smokers and non
      smokers. A prospective cross-sectional study.
AB  - BACKGROUND: The poor air quality and cigarette smoking are the most important
      reasons for increased carbon monoxide (CO) level in exhaled air. However, the
      influence of high air pollution concentration in big cities on the exhaled CO
      level has not been well studied yet. OBJECTIVES: To evaluate the impact of
      smoking habit and air pollution in the place of living on the level of CO in
      exhaled air. METHODS: Citizens from two large cities and one small town in Poland
      were asked to complete a survey disclosing their place of residence, education
      level, work status and smoking habits. Subsequently, the CO level in their
      exhaled air was measured. Air quality data, obtained from the Regional
      Inspectorates of Environmental Protection, revealed the differences in
      atmospheric CO concentration between locations. RESULTS: 1226 subjects were
      divided into 4 groups based on their declared smoking status and place of living.
      The average CO level in exhaled air was significantly higher in smokers than in
      non-smokers (p<0.0001) as well as in non-smokers from big cities than non-smokers
      from small ones (p<0.0001). Created model showed that non-smokers from big cities
      have odds ratio of 125.3 for exceeding CO cutoff level of 4ppm compared to non
      smokers from small towns. CONCLUSIONS: The average CO level in exhaled air is
      significantly higher in smokers than non-smokers. Among non-smokers, the average
      exhaled CO level is significantly higher in big city than small town citizens.
      These results suggest that permanent exposure to an increased concentration of
      air pollution and cigarette smoking affect the level of exhaled CO.

PMID- 27712839
TI  - ?

PMID- 27712840
TI  - Development and psychometric testing of a measure of older adult patients'
      attitudes towards mobility during hospitalization (ATM-H).
AB  - This paper describes the development and psychometric testing of a questionnaire
      evaluating attitudes towards mobility during hospitalization of older adults, an
      understudied phenomenon that lacks a valid and reliable measure. An instrument
      development procedure, followed by an empirical study, was conducted between
      December 2013 and June 2014. Instrument development included item generation and
      analysis of content validity, which was established by six experts. The
      validation study used a prospective within-patients design with a sample of 100
      patients, age 70+, hospitalized in general medical units in a large medical
      center. Internal consistency, reliability, and divergent and predictive validity
      of the measure were tested. Reliability analysis revealed an acceptable estimate
      for the total score (0.76). Predictive validity was good. The divergent validity
      coefficient was in the expected direction. Preliminary psychometric properties of
      the measure showed acceptable results. The measure should be explored further in
      different cultural settings.

PMID- 27712841
TI  - Frailty defined by the SHARE Frailty Instrument and adverse outcomes after an ED
      visit.

PMID- 27712842
TI  - A lethal case of gastroenterobronchial fistula.

PMID- 27712843
TI  - Impact of concierges on ED revisits and outpatient follow-up.

PMID- 27712844
TI  - Prenatal versus Postnatal Screening for Familial Retinoblastoma.
AB  - PURPOSE: To compare overall outcomes of conventional postnatal screening of
      familial retinoblastoma and prenatal RB1 mutation identification followed by
      planned early-term delivery. DESIGN: Retrospective, observational study.
      PARTICIPANTS: Twenty children with familial retinoblastoma born between 1996 and
      2014 and examined within 1 week of birth. METHODS: Cohort 1 included
      spontaneously delivered neonates examined within 1 week of birth and confirmed
      postnatal to carry their family's RB1 mutant allele. Cohort 2 included infants
      identified by amniocentesis to carry their family's RB1 mutant allele, and
      therefore scheduled for early-term delivery (36-38 weeks' gestation). Treatment
      for retinoblastoma was performed at the Hospital for Sick Children, Toronto,
      Canada. MAIN OUTCOME MEASURES: Age at first tumor in each eye, eye stage,
      treatments given, ocular salvage, treatment success (defined as avoidance of
      enucleation, external-beam irradiation, or both), visual outcome, number of
      anesthetics, pregnancy or delivery complications, and estimated treatment burden.
      RESULTS: Vision-threatening tumors were present at birth in 4 of 8 infants in
      cohort 1 and in 3 of 12 infants in cohort 2. Eventually, all infants demonstrated
      tumors in both eyes. At the first treatment, 1 of 8 infants in cohort 1 had eyes
      in stage cT1a/cT1a or cT1a/cT0 (smallest and least vision-threatening tumors),
      compared with 8 of 12 infants in cohort 2 (P = 0.02). Null RB1 germline alleles
      induced earlier tumors than low-penetrance alleles (P = 0.03). Treatment success
      was achieved in 3 of 8 children in cohort 1 compared with 11 of 12 children in
      cohort 2 (P = 0.002). Acceptable vision (better than 0.2 decimal) was achieved
      for 8 of 16 eyes in cohort 1 compared with 21 of 24 eyes in cohort 2 (P = 0.014).
      Useful vision (better than 0.1, legal blindness) was achieved for 8 of 9 children
      in cohort 1 compared with 12 of 12 children in cohort 2. There were no
      complications related to early-term delivery. Median follow-up was 5.6 years,
      cohort 1 and 5.8 years, cohort 2. CONCLUSIONS: When a parent had retinoblastoma,
      prenatal molecular diagnosis with early-term delivery increased the likelihood of
      infants born with no detectable tumors, better vision outcomes, and less invasive
      therapy. Prenatal molecular diagnosis facilitates anticipatory planning for both
      the child and family.

PMID- 27712846
TI  - Methylation of the circadian Clock gene in the offspring of a free-living
      passerine bird increases with maternal and individual exposure to PM10.
AB  - The consequences of exposure to particulate matter (PM) have been thoroughly
      investigated in humans and other model species, but there is a dearth of studies
      of the effects of PM on physiology and life-history traits of non-human organisms
      living in natural or semi-natural environments. Besides toxicological relevance,
      PM has been recently suggested to exert epigenetic effects by altering DNA
      methylation patterns. Here, we investigated for the first time the association
      between the exposure to free-air PM10 and DNA methylation at two loci ('poly-Q
      exon' and '5'-UTR') of the Clock gene in blood cells of the nestlings of a
      synanthropic passerine bird, the barn swallow (Hirundo rustica). The Clock gene
      is a phylogenetically highly conserved gene playing a major role in governing
      circadian rhythms and circannual life cycles of animals, implying that change in
      its level of methylation can impact on important fitness traits. We found that
      methylation at both loci significantly increased with PM10 levels recorded few
      days before blood sampling, and also with PM10 exposure experienced by the mother
      during or shortly before egg laying. This study is the first where methylation at
      a functionally important gene has been shown to vary according to the
      concentration of anthropogenic pollutants in any animal species in the wild.
      Since early-life environmental conditions produce epigenetic effects that can
      transgenerationally be transmitted, DNA methylation of genes controlling
      photoperiodic response can have far reaching consequences for the ecology and the
      evolution of wild animal populations.

PMID- 27712847
TI  - Invasive Haemophilus influenzae serotype b disease in adults.

PMID- 27712848
TI  - First case of ceftazidime/avibactam administration in home care. ESBL producing
      Klebsiella pneumoniae bacteremia.

PMID- 27712845
TI  - Pharmacogenetic Optimization of Smoking Cessation Treatment.
AB  - Worldwide, approximately one billion people smoke cigarettes. Cigarette smoking
      persists in part because long-term smoking cessation rates are modest on existing
      treatments. Smoking cessation outcomes are influenced by genetic factors,
      including genetic variation in enzymes that metabolize nicotine and smoking
      cessation medications, as well as in receptor targets for nicotine and treatment
      medications. For example, smokers with genetically slow nicotine metabolism have
      higher cessation success on behavioural counseling and nicotine patches compared
      with smokers with genetically fast nicotine metabolism. In this review, we
      highlight new progress in our understanding of how genetic variation in the
      pharmacological targets of nicotine and smoking cessation medications could be
      used to tailor smoking cessation therapy, increase quit rates, and reduce tobacco
      related harm.

PMID- 27712849
TI  - A safe an easy method for building consensus HIV sequences from 454 massively
      parallel sequencing data.
AB  - OBJECTIVE: To show how to generate a consensus sequence from the information of
      massive parallel sequences data obtained from routine HIV anti-retroviral
      resistance studies, and that may be suitable for molecular epidemiology studies.
      MATERIAL AND METHODS: Paired Sanger (Trugene-Siemens) and next-generation
      sequencing (NGS) (454 GSJunior-Roche) HIV RT and protease sequences from 62
      patients were studied. NGS consensus sequences were generated using Mesquite,
      using 10%, 15%, and 20% thresholds. Molecular evolutionary genetics analysis
      (MEGA) was used for phylogenetic studies. RESULTS: At a 10% threshold, NGS-Sanger
      sequences from 17/62 patients were phylogenetically related, with a median
      bootstrap-value of 88% (IQR83.5-95.5). Association increased to 36/62 sequences,
      median bootstrap 94% (IQR85.5-98)], using a 15% threshold. Maximum association
      was at the 20% threshold, with 61/62 sequences associated, and a median bootstrap
      value of 99% (IQR98-100). CONCLUSION: A safe method is presented to generate
      consensus sequences from HIV-NGS data at 20% threshold, which will prove useful
      for molecular epidemiological studies.

PMID- 27712850
TI  - Management Difficulties in a Patient with EGFR-mutation Positive Lung
      Adenocarcinoma and Cerebral Metastases.

PMID- 27712851
TI  - Dogmas and medical beliefs in COPD.

PMID- 27712852
TI  - Renin-Angiotensin System Blockade and Long-term Clinical Outcomes in Kidney
      Transplant Recipients: A Meta-analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Renin-angiotensin system [RAS] blockade has been established as the
      cornerstone of therapy in the general population, and especially in chronic
      kidney disease. However, its efficacy in the kidney transplant population remains
      unknown. STUDY DESIGN: We conducted a systematic review and meta-analysis using
      MEDLINE (1966 to November 2015), Embase (1980 to November 2015), and the Cochrane
      Library (third quarter 2015), as well as a PubMed search for recent nonindexed
      citations. SETTINGS & POPULATION: Adult kidney transplant recipients. SELECTION
      CRITERIA FOR STUDIES: Randomized controlled trials, with follow-up of 1 year or
      longer and reporting clinical outcomes of interest. INTERVENTION: RAS blockade
      (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers)
      versus placebo, active comparator, or standard of care. OUTCOMES: All-cause
      mortality, all-cause transplant failure, and doubling of serum creatinine level.
      RESULTS: 8 trials (1,502 participants) were included in the systematic review.
      RAS blockade did not significantly alter all-cause mortality (risk ratio [RR],
      0.96; 95% CI, 0.62-1.51), transplant failure (RR, 0.76; 95% CI, 0.49-1.18), or
      creatinine level doubling (RR, 0.84; 95% CI, 0.51-1.39) compared to the control
      group. This result was robust across the subgroups of interest (angiotensin
      converting enzyme inhibitor or angiotensin receptor blocker intervention, follow
      up >= 1 year, and baseline proteinuria as an inclusion criterion). There was
      significantly higher risk for hyperkalemia with RAS blockade (RR, 2.44; 95% CI,
      1.53-3.90). There was no statistical heterogeneity in any of these pooled
      analyses. LIMITATIONS: Relatively smaller number of events (overall, 71 deaths
      and 72 transplant failures among 8 trials) and relatively short follow-up (only 2
      trials > 5 years). CONCLUSIONS: This analysis neither supports nor refutes the
      hypothesis that RAS blockade improves clinical outcomes in kidney transplant
      recipients. A trial with more than 10,000 patients would be needed to
      definitively answer whether RAS blockade reduces transplant loss in this
      population. In the meantime, clinicians should weigh the risks and benefits of
      using these medications with their patients on a case-by-case basis.

PMID- 27712853
TI  - Commercial vaccines provide limited protection to NADC30-like PRRSV infection.
AB  - NADC30-like PRRSV has been recently reported and became endemic in vaccinated pig
      herds in China. The outbreaks of disease in vaccinated pigs indicated the
      inefficacy of commercial PRRSV vaccines. In this study, five commercial PRRSV
      vaccines that have been widely used in China were used to evaluate the efficacy
      to a NADC30-like PRRSV infection. The vaccinated pigs were challenged with
      HNjz15, a NADC30-like PRRSV at 28days post vaccination. Compared to unvaccinated
      pigs, the vaccinated pigs clinically shortened the period of fever with less pig
      numbers of clinical manifestations and had improved body weight gain at the end
      of the study. However, the vaccinated pigs developed viremia with similar
      kinetics and suffered pathological lesions in lung and lymphoid tissues as the
      unvaccinated pigs. The virus load in tonsil, lung and lymph nodes detected by
      immunohistochemistry staining in vaccinated pigs was also similar to that in
      unvaccinated pigs which indicated the inability of vaccination to eradicate the
      virus from tissues of vaccinated pigs. Therefore, the above results suggested
      current commercial PRRSV vaccines could not provide complete protection to the
      NADC30-like PRRSV infection.

PMID- 27712854
TI  - A Hidden Cause of Hemorrhage: Cavernous Venous Malformation.

PMID- 27712855
TI  - Patient selection does not improve the success rate of infected TKA one stage
      exchange.
AB  - BACKGROUND: One stage exchange of a chronically infected total knee arthroplasty
      (TKA) is recommended in selected cases only. However, there is little evidence
      regarding the usefulness of selection criteria. The goal of this retrospective
      study was to compare the results of two concomitant cohorts of patients with
      chronically infected TKA: one treated with a routine one-stage exchange (study
      group) and one treated with one-stage exchange in selected cases only (control
      group). The hypoyhesis tested was that the failure rate and repeat surgery rate
      were higher in the study group than in the control group. METHODS: One hundred
      and thirty one cases were selected: 54 in the study group and 77 in the control
      group. There were 63 men and 68 women with a mean age of 70years. All patients
      were followed up for a minimal period of time of two years or until death or
      recurrence of infection. RESULTS: Twenty five cases had a recurrence of
      infection: 9/54 in the study group and 16/77 in the control group (NS). The
      survival rate for being free of infection after four years was 85% in the study
      group and 78% in the control group (NS). The repeat surgery rate was
      significantly higher in the control group. CONCLUSION: The tested hypothesis was
      rejected. When one stage exchange is considered, patient selection does not
      improve outcome.

PMID- 27712856
TI  - Knee joint position sense ability in elite athletes who have returned to
      international level play following ACL reconstruction: A cross-sectional study.
AB  - BACKGROUND: Following an ACL injury, reconstruction (ACL-R) and rehabilitation,
      athletes may return to play with a proprioceptive deficit. However, literature is
      lacking to support this hypothesis in elite athletic groups who have returned to
      international levels of performance. It is possible the potentially heightened
      proprioceptive ability evidenced in athletes may negate a deficit following
      injury. The purpose of this study was to consider the effects of ACL injury,
      reconstruction and rehabilitation on knee joint position sense (JPS) on a group
      of elite athletes who had returned to international performance. METHODS: Using a
      cross-sectional design ten elite athletes with ACL-R and ten controls were
      evaluated. JPS was tested into knee extension and flexion using absolute error
      scores. Average data with 95% confidence intervals between the reconstructed,
      contralateral and uninjured control knees were analyzed using t-tests and effect
      sizes. RESULTS: The reconstructed knee of the injured group demonstrated
      significantly greater angle of error scores when compared to the contralateral
      and uninjured control into knee flexion (p=0.0001, r=0.98) and knee extension
      (p=0.0001, r=0.91). There were no significant differences between the
      contralateral uninjured knee of the injured group and the uninjured control
      group. CONCLUSIONS: Elite athletes who have had an ACL injury, reconstruction,
      rehabilitation and returned to international play demonstrate lower JPS ability
      compared to control groups. It is unclear if this deficiency affects long-term
      performance or secondary injury and re-injury problems. In the future physical
      therapists should monitor athletes longitudinally when they return to play.

PMID- 27712857
TI  - Removable air-cathode to overcome cathode biofouling in microbial fuel cells.
AB  - An innovative microbial fuel cell (MFC) design is described, which allows the air
      cathode to be replaced easily without draining the electrolyte. MFCs equipped
      with 9-cm2 or 50-cm2 bioanodes provided 0.6 and 0.7W/m2 (referred to the cathode
      surface area) and were boosted to 1.25 and 1.96W/m2, respectively, when the
      initial air-cathode was replaced by a new one. These results validate the
      practical interest of removable air-cathodes and evidence the importance of the
      cathode biofouling that takes place during the MFC starting phase. As this
      biofouling is compensated by the concomitant improvement of the bioanodes it
      cannot be detected on the power curves and may be a widespread cause of
      performance underestimation.

PMID- 27712858
TI  - Fine mapping of the GWAS loci identifies SLC35D1 and IL23R as potential risk
      genes for leprosy.
AB  - BACKGROUND: Previous genome-wide association study (GWAS) identified two new
      leprosy associated loci (1p31.3 [rs3762318] and 6q24.3 [rs2275606]). However,
      there were insufficient validations in independent populations. OBJECTIVE: To
      validate the association and to map the potentially causal variants/genes
      underlying the association between the confirmed GWAS hit and leprosy. METHODS:
      We genotyped 10 variants in the regions encompassing the two loci in 1110 Han
      Chinese subjects with and without leprosy, followed by expression quantitative
      trait loci (eQTL), mRNA expression profiling, and network analysis. We further
      sequenced the exon region of four genes that were located in the confirmed GWAS
      hit region in 80 leprosy patients and 99 individuals without leprosy. RESULTS: We
      validated the positive association of rs3762318 with multibacillary leprosy
      (P=7.5*10-4), whereas the association of rs2275606 could not be validated. eQTL
      analysis showed that both the GWAS locus rs3762318 and one surrounding positively
      associated SNP rs2144658 (P=1.8*10-3) significantly affected the mRNA expression
      of a nearby gene SLC35D1, which might be involved in metabolism. Moreover,
      SLC35D1 was differentially expressed in skin tissues of leprosy patients, and the
      differential expression pattern was consistent among leprosy subtypes. Rare
      damaging missense variants in IL23R were significantly enriched in leprosy
      patients. CONCLUSION: Our results supported the positive association between the
      GWAS reported rs3762318 and leprosy, and SLC35D1 and IL23R might be the causal
      genes.

PMID- 27712859
TI  - Foeniculum vulgare extract and its constituent, trans-anethole, inhibit UV
      induced melanogenesis via ORAI1 channel inhibition.
AB  - BACKGROUND: Ultraviolet radiation exposure is the most important cause of
      extrinsic skin aging (photoaging), which causes skin wrinkling and
      hyperpigmentation. Although many factors are involved in the photoaging process,
      calcium release-activated calcium channel protein 1 (ORAI1) has been reported to
      be involved in UV-induced melanogenesis. OBJECTIVE: The aim of the present study
      was to find inhibitory effects of the extract of Foeniculum vulgare (fennel)
      fruits on ORAI1 ion channels and UV-induced melanogenesis in melanoma cells and
      to identify its active constituents. METHODS: Active compounds were isolated and
      quantitatively analyzed. An electrophysiological assay was performed by using the
      whole-cell patch-clamp technique. Intracellular free calcium concentration was
      measured by Fura-2. Tyrosinase activity was evaluated by levodopa colorimetry.
      Effects of the most active compound on cell viability of murine B16F10 melanoma
      cells and inhibition of melanin content after UVB irradiation were determined.
      RESULTS: F. vulgare fruits extract and its hexane fraction strongly blocked ORAI1
      currents and tyrosinase activity and significantly inhibited UV-induced
      melanogenesis. Of the 13 compounds isolated from the hexane fraction, trans
      anethole (TA) exhibited inhibitory effects on ORAI1 (IC50=8.954+/-1.36MUM) and
      increased cytoplasmic Ca2+ concentrations in response. TA inhibited UV-induced
      melanogenesis without affecting tyrosinase activity. CONCLUSION: Our findings
      suggest that the fruits extract of F. vulgare and its active constituent, TA,
      provide a possible novel approach for treating and preventing UV-induced
      melanogenesis.

PMID- 27712860
TI  - A high-resolution operational forecast system for oil spill response in Belfast
      Lough.
AB  - This paper presents a high-resolution operational forecast system for providing
      support to oil spill response in Belfast Lough. The system comprises an
      operational oceanographic module coupled to an oil spill forecast module that is
      integrated in a user-friendly web application. The oceanographic module is based
      on Delft3D model which uses daily boundary conditions and meteorological forcing
      obtained from COPERNICUS and from the UK Meteorological Office. Downscaled
      currents and meteorological forecasts are used to provide short-term oil spill
      fate and trajectory predictions at local scales. Both components of the system
      are calibrated and validated with observational data, including ADCP data, sea
      level, temperature and salinity measurements and drifting buoys released in the
      study area. The transport model is calibrated using a novel methodology to obtain
      the model coefficients that optimize the numerical simulations. The results
      obtained show the good performance of the system and its capability for oil spill
      forecast.

PMID- 27712862
TI  - Chemogenetic activation of dopamine neurons in the ventral tegmental area, but
      not substantia nigra, induces hyperactivity in rats.
AB  - Hyperactivity is a core symptom in various psychiatric disorders, including
      attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorders, and
      anorexia nervosa. Although hyperactivity has been linked to dopaminergic
      signalling, the causal relationship between midbrain dopamine neuronal activity
      and locomotor hyperactivity remains unknown. In this study, we test whether
      increased dopamine neuronal activity is sufficient to induce locomotor
      hyperactivity. To do so, we used designer receptors exclusively activated by
      designer drugs (DREADD) to chemogenetically enhance neuronal activity in two main
      midbrain dopamine neuron populations, i.e. the ventral tegmental area (VTA) and
      substantia nigra pars compacta (SN), in TH:Cre rats. We found that activation of
      VTA dopamine neurons induced a pronounced and long-lasting hyperactive phenotype,
      whilst SN dopamine neuron activation only modestly increased home cage
      locomotion. Furthermore, this hyperactive phenotype was replicated by selective
      activation of the neuronal pathway from VTA to the nucleus accumbens (NAC). These
      results show a clear functional difference between neuronal subpopulations in the
      VTA and SN with regards to inducing locomotor hyperactivity, and suggest that the
      dopaminergic pathway from VTA to NAC may be a promising target for the treatment
      of hyperactivity disorders.

PMID- 27712861
TI  - Occurrence and distribution of bacteria indicators, chemical tracers and
      pathogenic vibrios in Singapore coastal waters.
AB  - Water quality in Singapore's coastal area was evaluated with microbial
      indicators, pathogenic vibrios, chemical tracers and physico-chemical parameters.
      Sampling sites were grouped into two clusters (coastal sites at (i) northern and
      (ii) southern part of Singapore). The coastal sites located at northern part of
      Singapore along the Johor Straits exhibited greater pollution. Principal
      component analysis revealed that sampling sites at Johor Straits have greater
      loading on carbamazepine, while turbidity poses greater influence on sampling
      sites at Singapore Straits. Detection of pathogenic vibrios was also more
      prominent at Johor Straits than the Singapore Straits. This study examined the
      spatial variations in Singapore's coastal water quality and provided the baseline
      information for health risk assessment and future pollution management.

PMID- 27712863
TI  - Patients' Perceptions and Experiences of Shared Decision-Making in Primary HIV
      Care Clinics.
AB  - Shared decision-making (SDM) is considered best practice in health care. Prior
      studies have explored attitudes and barriers/facilitators to SDM, with few
      specific to HIV care. We interviewed 53 patients in HIV primary care clinics in
      California to understand the factors and situations that may promote or hinder
      engagement in SDM. Studies in other populations have found that patients'
      knowledge about their diseases and their trust in providers facilitated SDM. We
      found these features to be more nuanced for HIV. Perceptions of personal agency,
      knowledge about one's disease, and trust in provider were factors that could work
      for or against SDM. Overall, we found that participants described few experiences
      of SDM, especially among those with no comorbidities. Opportunities for SDM in
      routine HIV care (e.g., determining antiretroviral therapy) may arise
      infrequently because of treatment advances. These findings yield considerations
      for adapting SDM to fit the context of HIV care.

PMID- 27712864
TI  - Mean annual temperatures of mid-latitude regions derived from delta2H values of
      wood lignin methoxyl groups and its implications for paleoclimate studies.
AB  - Tree-rings are widely used climate archives providing annual resolutions on
      centennial to millennial timescales. Stable isotope ratios of tree-rings have
      been applied to assist with the delineation of climate parameters such as
      temperature and precipitation. Here, we investigated stable hydrogen isotope
      ratios (expressed as delta2H values) of lignin methoxyl groups of wood from
      various tree species collected along a ~3500km north-south transect across Europe
      with mean annual temperatures (MAT) ranging from -4 to +17 degrees C. We found a
      strong linear relationship between MATs and delta2H values of wood lignin
      methoxyl groups. We used this relationship to predict MATs from randomly
      collected wood samples and found general agreement between predicted and observed
      MATs for the mid-latitudes on a global scale. Our results are discussed in
      context of their paleoclimate relevance and suggest that delta2H values of lignin
      methoxyl groups might have the potential to reconstruct MATs when applied on mid
      latitudinal tree-ring chronologies of the Late Holocene.

PMID- 27712865
TI  - Artificial macropores attract crop roots and enhance plant productivity on
      compacted soils.
AB  - The structure of compacted soils is characterised by decreased (macro-)porosity,
      which leads to increased mechanical impedance and decreased fluid transport
      rates, resulting in reduced root growth and crop productivity. Particularly in
      soils with high mechanical impedance, macropores can be used by roots as pathways
      of least resistance. This study investigated how different soil physical states
      relate to whole plant growth and whether roots grow towards spots with favourable
      soil physical conditions. Experiments were conducted under controlled and field
      conditions. Soybean (Glycine max L.), wheat (Triticum aestivum L.) and maize (Zea
      mays L.) were grown on uncompacted soil, compacted soil and compacted soil with
      artificial macropores. The interactions between roots and artificial macropores
      were quantified using X-ray computed tomography. Active growth of roots towards
      artificial macropores was observed for all three species. Roots grew either into
      macropores (predominantly in maize) or crossed them (predominantly in wheat). The
      presence of artificial macropores in compacted soil enabled all three species to
      compensate for decreased early vigour at later developmental stages. These
      results show that roots sense their physical environment, enabling them to grow
      towards spots with favourable soil conditions. The different kinds of root
      macropore interaction indicated that macropores serve as a path of least
      resistance and a source of oxygen, both resulting in increased crop productivity
      on compacted soils.

PMID- 27712866
TI  - Energy demand for elimination of organic micropollutants in municipal wastewater
      treatment plants.
AB  - Organic micropollutants (OMP), e.g. pharmaceuticals and household/industrial
      chemicals, are not fully eliminated in state-of-the-art municipal wastewater
      treatment plants and can potentially harm the aquatic environment. Therefore,
      several pilot and large-scale investigations on the elimination of organic
      micropollutants have taken place in recent years. Based on the present findings,
      the most efficient treatment steps to eliminate organic micropollutants have
      proven to be ozonation, adsorption on powdered activated carbon (PAC), or
      filtration through granular activated carbon (GAC). Yet a further treatment step
      implies an increase in energy demand of the wastewater treatment plant, which has
      to be considered along with OMP elimination. To this aim, data on energy demand
      of ten large-scale municipal wastewater treatment plants (WWTP) with processes
      for OMP elimination was collected and analyzed. Moreover, calculations on energy
      demand beyond the WWTP for production and transport of ancillary materials were
      performed to assess the cumulative energy demand of the processes. An assessment
      of the greenhouse gas emissions of the processes was achieved, which shall
      facilitate future life cycle analyses. The results show that energy demand of
      ozonation at the wastewater treatment plant is dependent upon the ozone dosage
      and is significantly higher than energy demand of PAC addition or GAC filtration
      (2 to 4 times higher without consideration of delivery heads). Despite
      uncertainties regarding the energy demand for production of activated carbon, it
      could be shown that the cumulative energy demand of adsorption steps is
      significantly higher than the energy demand at the WWTP. Using reactivated GAC
      can lead to energy and greenhouse gas emissions savings compared to using fresh
      GAC/PAC. Moreover, energy demand is always plant-specific and depends on
      different factors (delivery heads, existing filtration or post-treatment etc.).
      Since processes for elimination of organic micropollutants are still in a
      developing phase, future optimization steps shall minimize their energy demand.

PMID- 27712867
TI  - The water productivity score (WPS) at global and regional level: Methodology and
      first results from remote sensing measurements of wheat, rice and maize.
AB  - Scarce water resources are one of the major constraints to achieve more food
      production. Food production needs therefore also to be evaluated in terms of
      water consumption, besides the conventional unit of land. Crop Water Productivity
      (CWP) is defined as the crop yield per unit of water evaporated. Contrary to crop
      yield, local benchmark values for CWP do not exist. This paper shows how
      operational earth observation satellites can measure CWP indirectly on a pixel-by
      pixel basis, which provides an opportunity to define local, regional and global
      benchmark values. In analogy to a grading system for earthquakes (Richter) or
      wind force (Beaufort), a grading system for CWP is introduced: the Water
      Productivity Score (WPS). A regional scale WPS and a global version - Global
      Water Productivity Score (GWPS) - are presented. Crop yield zones are used to
      reflect local production potential, which reflects also the presence of
      irrigation systems besides general physio-graphical conditions. The 99th
      percentiles of climatic normalized CWP values at global scale are 2.45, 2.3 and
      4.9kgm-3 for wheat, rice and maize respectively. There is significant scope to
      produce the same - or more - food from less water resources, provided that
      locally specific best on-farm practices are implemented. At the upstream level,
      Governments can use (G)WPS to define national water and food policies and use it
      as a means to report to the Sustainable Development Goal standards. At the
      downstream level, WPS helps to improve on-farm water management practices by
      growers, both for rainfed and irrigated crops. While the current paper is based
      on wheat, rice and maize, the same framework can be expanded to potatoes,
      sugarbeet, sugarcane, fruit trees, cotton and other crops.

PMID- 27712868
TI  - Mass, nutrient pool, and mineralization of litter and fine roots in a tropical
      mountain cloud forest.
AB  - We used fine root and litter mass from a tropical mountain cloud forest to assess
      their relative contribution to nutrient content and to examine mineralization
      processes during a laboratory incubation experiment. Our results showed that
      average fine root mass density ranged from 2.86kgm-3 to 11.59kgm-3, while litter
      mass density ranged from 72.5kgm-3 to 177.3kgm-3. On average, fine root mass
      density represented 4.7% of the mass density of the O horizon. Fine root mass
      density followed an exponentially declining trend with soil depth. On average,
      83% of fine root mass density within the soil profile was concentrated in the O
      horizon. Mean element pools in litter decreased from 44.08mgcm-3 to 0.49MUgcm-3
      in the following sequence: C>N>Fe>S>Ca>P>K>Mg>Na>Mn>Zn>Cu. For fine roots, a
      different mean element pool sequence (C>N>Ca>K>Fe>S>Mg>Na>P>Mn>Zn>Cu) in
      decreasing abundance (from 2.88mgcm-3 to 0.13MUgcm-3) was observed with respect
      to litter. Regarding C, litter mineralized faster than fine roots, with a mean k
      value of 0.25d-1 for litter and 0.13d-1 for fine roots. Principal component
      analysis (PCA) combined with stepwise regression analysis revealed that the main
      mass density predictors were N, S, Zn, and Mn for litter (p<0.0001, R2=0.92), and
      S and C/N ratio for fine roots (p<0.0001, R2=0.82). These results demonstrate the
      potential of chemical composition to influence the mineralization of fine root
      and litter mass and therefore the nutrient availability and C sequestration.

PMID- 27712870
TI  - Hydrological responses to land use/cover changes in the source region of the
      Upper Blue Nile Basin, Ethiopia.
AB  - Understanding how changes in distinctive land use/land cover (LULC) types
      influence the basin hydrology would greatly improve the predictability of the
      hydrological consequences of LULC dynamics for sustainable water resource
      management. As the main flow contributor to the River Nile, quantifying the
      effect of LULC change on water resources in the source regions is very important
      for the assessment of water resources availability and management downstream in
      the riparian states in general and the study watersheds in particular. In this
      study, an integrated approach comprising hydrological modeling and partial least
      squares regression (PLSR) was used to quantify the contributions of changes in
      individual LULC classes to changes in hydrological components. Two watersheds,
      namely Lake Tana and Beles in the Upper Blue Nile Basin in Ethiopia, were
      considered for the conduction of hydrological modeling using LULC maps and the
      Soil and Water Assessment Tool (SWAT). In the Tana sub-basin, it is found that
      expansion of cultivation land and decline in woody shrub are the major
      contributors to the rise in surface run-off and to the decline in the groundwater
      component. Similarly, decline of woodland and expansion of cultivation land are
      the major contributors to the increase in surface run-off and water yield in the
      Beles sub-basin. Increased run-off and reduced baseflow and actual
      evapotranspiration would have negative impacts on water resources, especially in
      relation to erosion and sedimentation in the upper Blue Nile River Basin. As a
      result, expansion of cultivation land and decline in woody shrub/woodland appear
      to be major environmental stressors affecting local water resources. The wider
      implications of the hydrological changes on the Easter Nile water resources are
      briefly discussed. The approach to assessing changes in basin hydrology could
      generally be applied to a variety of other watersheds for which temporal digital
      LULC maps are available.

PMID- 27712869
TI  - Assessing the population equivalent and performance of wastewater treatment
      through the ratios of pharmaceuticals and personal care products present in a
      river basin: Application to the River Thames basin, UK.
AB  - The quality of surface waters in lowland rivers is largely dependent on the
      efficiency of wastewater treatment. Even in the developed countries, there have
      been difficulties in evaluating the effectiveness of wastewater management and
      the proportion of wastewater content (WWC) in the river, as well as in estimating
      the contributing human population. This study aimed to develop a wastewater
      quality and quantity assessment based on the occurrence of pharmaceuticals in the
      receiving waters. A survey of 53 pharmaceuticals in 324 samples (river water and
      influent and effluent of sewage (wastewater) treatment plants) was carried out in
      southern England in the River Thames catchment over four years. Carbamazepine was
      selected as stable marker and from its concentration WWC in the rivers and
      cumulative human populations along the catchment were estimated. The estimated
      population had a strong relationship (R2=0.94) with that reported by the local
      water company. The concentration ratio of the labile marker caffeine to
      carbamazepine indicated the efficiency of wastewater treatment in the different
      treatment systems (i.e. trickling filter or activated sludge) and in the
      receiving waters. The ratio in some river samples revealed unexpected discharges
      of untreated or poorly treated wastewater, with a total concentration of the
      analytes (up to 20MUg/L) five times higher than that in treated wastewater. Such
      information could be valuable to estimate the discharge or occurrence of not only
      non-targeted chemicals, but also pathogens within the basin.

PMID- 27712871
TI  - Risk assessment of replacing conventional P fertilizers with biomass ash:
      Residual effects on plant yield, nutrition, cadmium accumulation and mycorrhizal
      status.
AB  - Reutilizing biomass ashes in agriculture can substitute inputs of P from finite
      primary sources. However, recycling of ashes is disputed due to their content of
      toxic substances such as heavy metals. This study evaluates the potential risk of
      replacing easily soluble inorganic P fertilizer with P in biomass ashes in a
      barley crop grown on soil with adequate P status. Two contrasting doses of three
      different types of ashes were applied to an agricultural field with spring barley
      and compared to similar doses of triple-superphosphate fertilizer. In the second
      growing season after biomass ash application, grain, straw and root dry matter
      yield, and P and Cd uptake were determined. Resin-extractable P was measured in
      soil and the symbiotic arbuscular mycorrhizal fungal activity, colonization, and
      community composition were assessed. Crop yield was not affected by ash
      application, while P-uptake and mycorrhizal status were slightly enhanced with
      high ash applications. Changes to the mycorrhizal community composition were
      evident with high ash doses. Cadmium uptake in aboveground plant tissue was
      unaffected by ash treatments, but increased in roots with increasing doses.
      Consequently, we conclude that fertilization with biomass ashes can replace
      conventional fertilizers without risk to barley crops in the short term.

PMID- 27712872
TI  - Verification of the oncologic inferiority of percutaneous biliary drainage to
      endoscopic drainage: A propensity score matching analysis of resectable perihilar
      cholangiocarcinoma.
AB  - BACKGROUND: Percutaneous transhepatic biliary drainage is an established biliary
      drainage method but is associated with a potential risk of seeding metastasis.
      The aim of this retrospective study was to evaluate whether percutaneous
      transhepatic biliary drainage really increases seeding metastasis and worsens the
      postoperative survival in patients with resectable perihilar cholangiocarcinoma.
      METHODS: Patients who underwent resection for perihilar cholangiocarcinoma after
      percutaneous transhepatic biliary drainage or endoscopic biliary drainage were
      retrospectively reviewed. Seeding metastasis was defined as peritoneal/pleural
      dissemination and percutaneous transhepatic biliary drainage sinus tract
      recurrence. Univariate and multivariate analyses followed by propensity score
      matching were performed to adjust the data for the baseline characteristics of
      the percutaneous transhepatic biliary drainage and endoscopic biliary drainage
      patients. RESULTS: Of 320 resected patients, 168 underwent percutaneous
      transhepatic biliary drainage and the remaining 152 received endoscopic biliary
      drainage before operation. The survival of the percutaneous transhepatic biliary
      drainage patients was significantly lower than that of the endoscopic biliary
      drainage patients (37.0% vs 44.3% at 5 years, P = .019). Multivariate analyses
      showed that percutaneous transhepatic biliary drainage was an independent
      predictor of poor survival (P = .011) and a risk factor for seeding metastasis (P
      = .005). After propensity score matching (71 patients in each group), the
      survival of the percutaneous transhepatic biliary drainage patients was
      significantly worse than that of the endoscopic biliary drainage patients (P =
      .018). The estimated cumulative recurrence rate of seeding metastasis was
      significantly higher in the percutaneous transhepatic biliary drainage patients
      than in the endoscopic biliary drainage patients (P = .005), while the recurrence
      rates at other sites were similar between the 2 groups (P = .413). CONCLUSION:
      Percutaneous transhepatic biliary drainage increases the incidence of seeding
      metastasis and shortens the postoperative survival in patients with perihilar
      cholangiocarcinoma. Endoscopic biliary drainage is recommended as the optimal
      method for preoperative biliary drainage.

PMID- 27712873
TI  - Impact of different sarcopenia stages on the postoperative outcomes after radical
      gastrectomy for gastric cancer.
AB  - BACKGROUND: The association between sarcopenia and postoperative outcomes has
      been well reported. However, the impact of different sarcopenia stages on
      postoperative outcomes has never been investigated. METHODS: We conducted a
      large, prospective study of patients who underwent radical gastrectomy for
      gastric cancer from August 2014 to December 2015. Sarcopenia was staged as
      "presarcopenia," "sarcopenia," and "severe sarcopenia" according to the
      definition of the European Working Group on Sarcopenia in Older People.
      Univariate and multivariate analyses evaluating the risk factors for total,
      surgical, and medical complications were performed. RESULTS: A total of 470
      patients were included, in which 20.6%, 10%, and 6.8% of the patients were
      identified as having "presarcopenia," "sarcopenia," and "severe sarcopenia,"
      respectively. Postoperative complications, duration of hospital stays, and costs
      increased with advancing sarcopenia stages. Severe sarcopenia, visceral fat area
      to total abdominal muscle area ratio, American Society of Anesthesiologists grade
      III, and tumor located at the cardia were independent risk factors for total
      complications. Visceral fat area to total abdominal muscle area ratio and tumor
      located at the cardia were independent risk factors for operative complications.
      Presarcopenia, sarcopenia, and severe sarcopenia were all identified as
      independent risk factors for medical complications, as well as age >=75 years and
      Charlson Comorbidity Index. CONCLUSION: Patients had worse postoperative outcomes
      after gastric cancer operation with advancing sarcopenia stages. Severe
      sarcopenia, but not presarcopenia or sarcopenia, was an independent risk factor
      for total postoperative complications. The 3 sarcopenia stages independently
      influence medical but not surgical complications. Recognizing sarcopenia stages
      is important for preoperative risk stratification.

PMID- 27712874
TI  - Variability in postoperative resource utilization after pancreaticoduodenectomy:
      Who is responsible.
AB  - BACKGROUND: We aimed to quantify and predict variability that exists in resource
      utilization after pancreaticoduodenectomy and determine how such variability
      impacts postoperative outcomes. METHODS: The University HealthSystems Consortium
      database was queried for all pancreaticoduodenectomies performed between 2011
      2013 (n = 9,737). A composite resource utilization score was created using z
      scores of 8 clinically significant postoperative care delivery variables
      including number of laboratory tests, imaging tests, computed tomographic scans,
      days on antibiotics, anticoagulation, antiemetics, promotility agents, and total
      number of blood products transfused per patient. Logistic, Poisson, and gamma
      regression models were used to determine predictors of increased variability in
      care between patients. RESULTS: Having a high (versus low) resource utilization
      score after pancreaticoduodenectomy correlated with increased duration of stay;
      (odds ratio 2.28), cost (odds ratio 1.89), readmission rate (odds ratio 1.46),
      and mortality (odds ratio 7.54). Patient-specific factors were the strongest
      predictors and included extreme severity of illness (odds ratio 114), major
      comorbidities/complications (odds ratio 5.99), and admission prior to procedure
      (odds ratio 2.72; all P < .01). Surgeon and center volume were not associated
      with resource utilization. CONCLUSION: Public reporting of patient outcomes and
      resource utilization, invariably tied to reimbursement in the near future, should
      consider that much of the postoperative variability after complex pancreatic
      operation is related to patient-specific risk factors.

PMID- 27712875
TI  - Insurance status is associated with complex presentation among emergency general
      surgery patients.
AB  - BACKGROUND: The Affordable Care Act has the potential to significantly affect
      access to care for previously uninsured patients in need of emergency general
      surgical care. Our objective was to determine the relationship between insurance
      status and disease complexity at presentation among a national sample of
      emergency general surgical patients. METHODS: Data from the National Emergency
      Department Sample from 2006-2009 were queried to identify all patients aged 18-64
      years old admitted through the emergency department with a primary diagnosis of
      appendicitis, diverticulitis, inguinal hernia, or bowel obstruction. Primary
      outcome of complex presentation was defined as also presenting with generalized
      peritonitis, intra-abdominal abscess, perforated bowel, intestinal gangrene, or
      other disease-specific measures of complexity. We used multivariable logistic
      regression to determine the independent association between insurance status and
      complex presentation. Models accounted for patient- and hospital-level
      covariates. Counterfactual models were used to estimate the risk of complex
      presentation attributable to lack of insurance. RESULTS: A total of 1,373,659
      patients were included, with an overall uninsured rate of 12.3%. Uninsured
      patients had significantly higher, unadjusted rates of complex presentation, and
      uninsured payer status was independently associated with complex presentation
      (odds ratio 1.38, 95% confidence interval: 1.34-1.42). Counterfactual models
      suggest that having insurance would result in a 22.37% (95% confidence interval:
      22.35-22.39%) relative decline in risk of complex emergency general surgical
      presentation among the uninsured population. CONCLUSION: Insurance status is
      independently associated with severity of disease at presentation among emergency
      general surgical conditions nationally. In light of recently reaffirmed
      Affordable Care Act insurance expansion provisions, these results anticipate
      increased timely access to operative care for newly insured patients and a
      corresponding decline in complex, emergency general surgical presentations.

PMID- 27712876
TI  - Allicin ameliorates intraintestinal bacterial translocation after
      trauma/hemorrhagic shock in rats: The role of mesenteric lymph node dendritic
      cell.
AB  - BACKGROUND: Intestinal dendritic cells play important roles in regulating the
      function of the intestinal immune barrier and the intestinal bacterial
      translocation. In this study, we aim to investigate the effects of allicin on the
      function of mesenteric lymph node-dendritic cells after trauma/hemorrhagic shock.
      METHODS: One hundred and eight-four Sprague-Dawley rats were randomly assigned
      into a sham group (n = 46), sham + allicin group (n = 46), trauma/hemorrhagic
      shock group (n = 46), and trauma/hemorrhagic shock + allicin group (n = 46).
      Studies were performed on an in vivo model of spontaneously breathing rats with
      induced trauma/hemorrhagic shock. Allicin was diluted in resuscitation fluid and
      was administered through the right jugular vein. Flow cytometry was used to
      determine the expression of CD80, CD86, and major histocompatibility complex II
      (MHC II) on the surface of mesenteric lymph node-dendritic cells, as well as
      apoptosis. Intraintestinal bacterial translocation was monitored by using
      bioluminescent citrobacter. Intestinal permeability tests were conducted by using
      both FITC-Dextran and Ussing-Chember assay. RESULT: CD80 and MHC-II expression
      levels were downregulated in the trauma/hemorrhagic shock group compared with the
      sham and sham + allicin groups; however, the expression was upregulated after
      allicin treatment. Also, allicin could ameliorate the trauma/hemorrhagic shock
      induced increase in early apoptosis of mesenteric lymph node-dendritic cells. A
      significant increase was observed in the permeability of the intestinal barrier
      after severe traumatic shock, along with an obvious intraintestinal bacterial
      translocation to mesenteric lymph node. No difference was noticed in the
      bacterial translocation in mesenteric lymph node in the trauma/hemorrhagic shock
      group compared with trauma/hemorrhagic shock + allicin group (P = .589), which
      indicated allicin could not block bacterial translocation into mesenteric lymph
      node after trauma/hemorrhagic shock. However, it may increase the capacity of
      mesenteric lymph node to block intraintestinal bacterial translocation to
      extraintestinal organs as a statistical difference was noticed in the bacterial
      translocation in liver, blood, and spleen between trauma/hemorrhagic shock and
      trauma/hemorrhagic shock + allicin groups (P < .05). CONCLUSION:
      Trauma/hemorrhagic shock resulted in a decrease of mature mesenteric lymph node
      dendritic cells. Allicin treatment could block intraintestinal bacterial
      translocation through increasing the immunologic barrier function of mesenteric
      lymph node by modulating dendritic cells maturation.

PMID- 27712877
TI  - Safety and feasibility of phlebotomy with controlled hypovolemia to minimize
      blood loss in liver resections.
AB  - BACKGROUND: Liver resection can be associated with significant blood loss and
      transfusion. Whole blood phlebotomy is an under-reported technique, distinct from
      acute normovolemic hemodilution, the goal of which is to minimize blood loss in
      liver operation. This work sought to report on its safety and feasibility and to
      describe technical considerations. METHODS: Consecutive patients who had an
      elective liver resection and concurrent phlebotomy between 2013 and 2016 were
      examined prospectively. Formal Inclusion and exclusion criteria were defined a
      priori. All surgical indications were allowed. All procedures were carried out
      with a stated goal of low central venous pressure anesthesia (<5 cm H2O). The
      target phlebotomy volume was 7-10 mL/kg of patient body weight. The removed blood
      was not replaced by intravenous fluid. Removed blood was returned back to the
      patient after parenchymal transection. Safety end points were examined. A
      historic cohort (2010-2014) of major resections was included for comparison.
      RESULTS: A total of 37 patients underwent liver resection with phlebotomy (86%
      major) and 101 without. Half had metastatic colorectal cancer. The median
      phlebotomy volume was 7.2 mg/kg (4.7-10.2), yielding a median drop in central
      venous pressure of 3 cm H2O (0-15). Median blood loss was 400 vs 700 mL (P =
      .0016), and the perioperative transfusion rate was 8.1% vs 32% (P = .0048). There
      was no difference between the 2 groups in overall complications, mortality,
      intensive care admission, duration of stay, or end-organ ischemic complications.
      CONCLUSION: Whole blood phlebotomy with controlled hypovolemia prior to liver
      resection seems to be safe and feasible. Comparative studies are required to
      determine its effectiveness.

PMID- 27712878
TI  - Liver hypoxia as a trigger to liver regeneration: No more than another piece of
      the puzzle.

PMID- 27712879
TI  - Primary hyperparathyroidism with normal baseline intraoperative parathyroid
      hormone: A challenging population.
AB  - BACKGROUND: Patients with primary hyperparathyroidism and baseline intraoperative
      parathyroid hormone levels in the normal range are challenging. This study
      compares the predictive value of a commonly used intraoperative parathyroid
      hormone algorithm, a software model for cure prediction, and surgeon judgment in
      this population. METHODS: This was a retrospective review of consecutive patients
      who underwent parathyroidectomy for primary hyperparathyroidism at a single
      institution from March 2013 to October 2014. RESULTS: Of 541 operative patients,
      114 (21.1%) had a mean normal baseline intraoperative parathyroid hormone of <=69
      pg/mL (median 59.0 +/- 10.3; range 26-69). Of the 114 patients, 93 (81.6%) were
      women, median age was 61 years (range 18-88). Overall, 107/108 (99.1%) patients
      were cured; 47 (41.2%) patients had single adenomas, 16 (14%) had double
      adenomas, and 51 (44.7%) had multigland hyperplasia. Using the 50% decline
      algorithm, a correct prediction was made in 86 (75.4%) patients. Using the
      computer software, a correct prediction was made in 88 (77.2%) patients. Surgeon
      judgment, however, was 99.1% accurate. CONCLUSION: Patients with normal baseline
      intraoperative parathyroid hormone have a high incidence of multigland disease
      (58.8%), greater than reported previously. Current software modeling and the 50%
      decline algorithm are insufficient to predict cure in this population;
      intraoperative parathyroid hormone interpretation combined with operative
      findings and surgical judgment yield optimal outcomes.

PMID- 27712880
TI  - Peritonitis in Rwanda: Epidemiology and risk factors for morbidity and mortality.
AB  - BACKGROUND: Few studies discuss causes and outcomes of peritonitis in low-income
      settings. This study describes epidemiology of patients with peritonitis at a
      Rwandan referral hospital. Identification of risk factors associated with
      mortality and unplanned reoperation could improve management of peritonitis.
      METHODS: Data were collected on demographics, clinical presentation, operative
      findings, and outcomes for all patients with peritonitis. Multivariate regression
      analysis identified factors associated with in-hospital mortality and unplanned
      reoperation. RESULTS: A total of 280 patients presented with peritonitis over a 6
      month period. Causes of peritonitis were complications of intestinal obstruction
      (39%) and appendicitis (17%). Thirty-six (13%) patients required unplanned
      reoperation, and in-hospital mortality was 17%. Factors associated with increased
      odds of in-hospital mortality were unplanned reoperation (adjusted odds ratio
      34.12), vasopressor use (adjusted odds ratio 24.91), abnormal white blood cell
      count (adjusted odds ratio 12.6), intensive care unit admission (adjusted odds
      ratio 9.06), and American Society of Anesthesiologist score >=3 (adjusted odds
      ratio 7.80). Factors associated with increased odds of unplanned reoperation
      included typhoid perforation (adjusted odds ratio 5.92) and hypoxia on admission
      (adjusted odds ratio 3.82). CONCLUSION: Peritonitis in Rwanda presents with high
      morbidity and mortality. Minimizing delays in care is important, as many patients
      with intestinal obstruction present with features of peritonitis. A better
      understanding of patient care and management prior to arrival at the referral
      hospital is needed to identify areas for improvement at the health center and
      district hospital.

PMID- 27712881
TI  - Should we be following anti-factor Xa levels in patients receiving prophylactic
      enoxaparin perioperatively?

PMID- 27712882
TI  - Spatial frequency content of plantar pressure and shear profiles for diabetic and
      non-diabetic subjects.
AB  - How high does pressure and shear stress sensor resolution need to be in order to
      reliably measure the plantar pressure and shear profiles (PPSPs) under normal and
      diabetic feet? In this study, pressure and shear stress data were collected from
      26 total diabetic and control subjects using new instrumentation that measures
      vertical and horizontal force vectors of the plantar contact surface during
      multiple instances in the gait cycle. The custom built shear-and-pressure
      evaluating-camera-system (SPECS) performs simultaneous recordings of pressure and
      both components of the horizontal force vector (medio-lateral and antero
      posterior) at distinctive regions under one's foot, at a spatial resolution for
      each sensor equal to 1.6mm by 1.6mm. A linear interpolation method was used to
      simulate the effect of increasing sensor size on PPSPs. Ten square-shaped sensors
      were included in the analysis, having edge lengths of: (1.6mm, 3.2mm, 4.8mm,
      6.4mm, 8mm, 9.6mm, 11.2mm, 12.8mm, 14.4mm, and 16mm). A two-dimensional Discrete
      Fourier Transform was performed on each data set, for each of the ten sensor
      sizes. To quantify the difference between sensor sizes, a comparison was made
      using the maximum pressure and shear stress data over the entire plantar contact
      surface, equivalent to the peak of the spatial frequency spectrum. A reduction of
      5% of any component of the stress vector (i.e., pressure, or medio-lateral shear
      stress, or anter-posterior shear stress) due to an increase in sensor size was
      deemed significant. The results showed that a sensor measuring 9.6mm by 9.6mm
      caused meaningful reductions in all three stress components (p<0.001), whereas
      sensors measuring 1.6mm by 1.6mm, up to 4.8mm by 4.8mm, can capture the full
      range of spatial frequencies in both pressure and shear stress data.

PMID- 27712883
TI  - Effects of sex, age, body height and body weight on spinal loads: Sensitivity
      analyses in a subject-specific trunk musculoskeletal model.
AB  - Subject-specific parameters influence spinal loads and the risk of back disorders
      but their relative effects are not well understood. The objective of this study
      is to investigate the effects of changes in age (35-60 years), sex (male,
      female), body height (BH: 150-190cm) and body weight (BW: 50-120kg) on spinal
      loads in a full-factorial simulation using a personalized (spine kinematics,
      geometry, musculature and passive properties) kinematics driven musculoskeletal
      trunk finite element model. Segmental weight distribution (magnitude and location
      along the trunk) was estimated by a novel technique to accurately represent
      obesity. Five symmetric sagittal loading conditions were considered, and main
      effect plots and analyses of variance were employed to identify influential
      parameters. In all 5 tasks simulated, BW (98.9% in compression and 96.1% in
      shear) had the greatest effect on spinal loads at the L4-L5 and L5-S1 levels
      followed by sex (0.7% in compression and 2.1% in shear), BH (0.4% in compression
      and 1.5% in shear) and finally age (<5.4%). At identical BH and BW, spinal loads
      in females were slightly greater than those in males by ~4.7% in compression and
      ~8.7% in shear. In tasks with no loads in hands, BW-normalized spinal loads
      further increased with BW highlighting the exponential increase in spinal loads
      with BW that indicates the greater risk of back disorders especially in obese
      individuals. Uneven distribution of weight in obese subjects, with more BW placed
      at the lower trunk, further (though slightly <7.5%) increased spinal loads.

PMID- 27712884
TI  - Predicting protein partition coefficients in aqueous two phase system.
AB  - The present work aims to achieve an additional insight into the protein
      partitioning behavior in aqueous two phase systems (ATPSs), together with a study
      on the viability of a semi-empirical model based on continuum electrostatics to
      predict the protein partition characteristics. The partitioning behaviors of 14
      globular proteins, with different properties, were explored in three
      polymer/polymer ATPSs. By the Collander equation, a linear correlation between
      protein partitioning coefficients in all systems was observed. Using the semi
      empirical model it was possible to predict the partitioning behavior of proteins.
      The electrostatic energy depends on the protein size and ATPSs characteristics
      and varies in agreement with the difference in phase dielectric constants. Linear
      correlation of nonpolar energy, and the solvent accessible surface area was
      observed. Polymer structure and concentration have a significant influence on
      model viability. A good qualitative prediction of preferred phase for studied
      proteins was observed.

PMID- 27712885
TI  - Intelligent peak deconvolution through in-depth study of the data matrix from
      liquid chromatography coupled with a photo-diode array detector applied to
      pharmaceutical analysis.
AB  - Multivariate curve resolution-alternating least squares (MCR-ALS) method was
      investigated for its potential to accelerate pharmaceutical research and
      development. The fast and efficient separation of complex mixtures consisting of
      multiple components, including impurities as well as major drug substances,
      remains a challenging application for liquid chromatography in the field of
      pharmaceutical analysis. In this paper we suggest an integrated analysis
      algorithm functioning on a matrix of data generated from HPLC coupled with photo
      diode array detector (HPLC-PDA) and consisting of the mathematical program for
      the developed multivariate curve resolution method using an expectation
      maximization (EM) algorithm with a bidirectional exponentially modified Gaussian
      (BEMG) model function as a constraint for chromatograms and numerous PDA spectra
      aligned with time axis. The algorithm provided less than +/-1.0% error between
      true and separated peak area values at resolution (Rs) of 0.6 using simulation
      data for a three-component mixture with an elution order of a/b/c with similarity
      (a/b)=0.8410, (b/c)=0.9123 and (a/c)=0.9809 of spectra at peak apex. This
      software concept provides fast and robust separation analysis even when method
      development efforts fail to achieve complete separation of the target peaks.
      Additionally, this approach is potentially applicable to peak deconvolution,
      allowing quantitative analysis of co-eluted compounds having exactly the same
      molecular weight. This is complementary to the use of LC-MS to perform
      quantitative analysis on co-eluted compounds using selected ions to differentiate
      the proportion of response attributable to each compound.

PMID- 27712886
TI  - Chromatographic behaviour of synthetic high pressure high temperature diamond in
      aqueous normal phase chromatography.
AB  - The chromatographic properties of high pressure high temperature synthesised
      diamond (HPHT) are investigated under the conditions of hydrophilic interaction
      liquid chromatography (HILIC). A 50*4.6mm ID stainless steel column packed with
      HPHT particles of mean diameter 1.6MUm and specific surface area 5.1m2g-1 is
      used. According to the results of acid-base titration with NaOH the purified HPHT
      batch contains 4.59MUeqg-1 of protogenic, mainly carboxyl- and hydroxyl-, groups,
      which make this polar adsorbent suitable for use as a stationary phase in HILIC.
      The retention behaviour of several classes of polar compounds including benzoic
      and benzenesulfonic acids, nitro- and chlorophenols, various organic bases, and
      quaternary ammonium compounds are studied using acetonitrile and methanol based
      mobile phases containing 5-30v/v% of water. The effects of the buffer pH and
      concentration, column temperature and organic solvent content on retention of
      model compounds are also investigated. It is shown that both pH and
      acetonitrile/methanol ratio in the mobile phase can be used to vary the
      separation selectivity. Molecular adsorption mechanism (related to aqueous normal
      phase mode), rather than partitioning is established to be responsible for the
      retention.

PMID- 27712888
TI  - Oral antibiotics for perforated appendicitis in children.

PMID- 27712887
TI  - Resectability and tumor response after preoperative chemotherapy in
      hepatoblastoma treated by the Japanese Study Group for Pediatric Liver Tumor
      (JPLT)-2 protocol.
AB  - BACKGROUND/PURPOSE: We aimed to clarify whether surgical resectability and tumor
      response after preoperative chemotherapy (preCTx) represented prognostic factors
      for patients with hepatoblastoma (HBL) in the JPLT-2 study (1999-2012). METHODS:
      Patients (N=342) with HBL who underwent preCTx were eligible. PRETEXT, CHIC risk
      stratification (standard [SR], intermediate [IR] and high risk [HR]) at
      diagnosis, POST-TEXT, and tumor resectability were evaluated by imaging. Tumor
      response was classified into responders (CR or PR) and nonresponders (NC or PD)
      according to RECIST criteria. RESULTS: There were 7 PRETEXT I, 106 II, 143 III,
      and 86 IV, including 71 metastatic HBLs. In POST-TEXT, 12 PRETEXT II, 42 III, and
      58 IV were down-staged. The 5-year EFS/OS rates of 198 SR, 73 IR, and 71 HR-HBLs
      were 82/94%, 49/64%, and 28/34%, respectively. In 198 SR, 154 of 160 responders
      and 24 of 38 nonresponders survived event-free (P<0.01). In 73 IR, 12 of 24 whose
      tumors remained unresectable experienced recurrence, 9 of whom were nonresponders
      (P<0.01). In 71 HR, chemoresponders and tumor resectability after preCTx
      correlated with favorable outcomes (P<0.05). CONCLUSIONS: Evaluation of response
      and tumor resectability after preCTx is useful for predicting prognosis in HBLs.
      To improve outcomes, we should reconsider surgical procedures according to
      resectability and chemoresponsiveness. LEVEL OF EVIDENCE: Level II.

PMID- 27712890
TI  - Acute gastrointestinal compromise in neonates with congenital diaphragmatic
      hernia prior to repair.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) affects 1 in 3000 live births.
      Modern management strategies include delayed repair of the diaphragm to permit
      pre-operative optimization of cardiorespiratory status. We describe a cohort of
      neonates in whom early emergency operative intervention was required for
      potentially fatal intestinal compromise. METHODS: A retrospective review was
      performed of all neonatal CDH patients managed at a tertiary center in an 8-year
      period (2005-2012). RESULTS: A total of 126 CDH patients were managed during the
      8-year period. Five neonates (male - 1; gestation 37+4-39+7; birth weight 2.9
      3.7kg; left CDH - 5) required emergency operative intervention for presumed
      gastrointestinal compromise. All five neonates demonstrated systemic hypotension
      despite inotropic support, raised serum lactate (>2mmol/L), and abnormal
      radiographic findings. Operative intervention occurred within 3days of birth (1
      3days). Findings included gastric volvulus, jejunal volvulus, and perforated
      caecum. All patients underwent primary diaphragmatic repair without a patch.
      Temporary ileostomy was required in 1 patient. All patients remain alive.
      CONCLUSION: Gastrointestinal compromise is a rare, but potentially catastrophic,
      complication of CDH. Emergency operative intervention may be required in a select
      cohort of patients. Early deterioration following birth should alert clinicians
      to the possibility of significant intestinal pathology. LEVEL OF EVIDENCE: Level
      IV case series with no comparison group.

PMID- 27712889
TI  - Magnetic resonance imaging of epiploic appendagitis in children.
AB  - In children, epiploic appendagitis has been seldom reported. We describe two
      children with clinical presentations mimicking appendicitis. A correct diagnosis
      was eventually achieved by magnetic resonance imaging (MRI) and confirmed at
      laparoscopy in the initial case. Our preliminary experience suggests that MRI is
      a valid and non-invasive alternative to computed tomography for characterization
      of unusual causes of pediatric abdominal pain in the acute hospital care setting.

PMID- 27712891
TI  - Usefulness of posterior sagittal anorectoplasty for redo pull-through in
      complicated and recurrent Hirschsprung disease: Experience with a single surgical
      group.
AB  - AIM: To retrospectively examine 12 patients with Hirschsprung disease (HD) who
      underwent posterior sagittal anorectoplasty (PSARP) for various complications.
      METHODS: This study included patients with HD who underwent redo pull-through
      (PT) via PSARP at our institute between 2005 and 2014. The type of initial
      procedure, clinical presentations, indications, and functional results were
      analyzed. Postoperative excretory function was assessed using the Krickenbeck
      classification. RESULTS: The study group comprised 9 boys and 3 girls (total,
      12). Five patients were diagnosed with rectosigmoid aganglionosis, 5 with long
      segment aganglionosis, and 2 with total colonic aganglionosis. The primary
      operations performed on these patients included the Soave, Duhamel, Swenson,
      Rehbein, and Ikeda-Soper procedures. The interval between the primary operations
      and reoperation ranged from 5months to 8years (median, 3years). The indications
      for PSARP were rectocutaneous fistulae (6 cases), frozen pelvis (5 cases), severe
      anastomotic stricture (3 cases), rectovaginal fistulae (2 cases), and hemorrhagic
      proctitis with an inflammatory polyp (1 case). All fistulae were repaired using
      PSARP; only one rectocutaneous fistula recurred and required two additional
      surgeries. Stricture and hemorrhagic proctitis were cured in all involved cases.
      Nine patients were followed up for 8months to 10years after PSARP surgery
      (average, 5.1years). All 9 patients had voluntary bowel movements within 6months
      after the last PSARP and stoma closure: 3 had normal bowel movement, while 6 had
      varying degrees of soiling, depending on the length of residual colon. None
      complained of constipation. CONCLUSION: PSARP is useful for treating severe
      complications of failed PT in HD. Complex and recurrent rectocutaneous fistulae
      and frozen pelvis are the main indications for PSARP, while soiling is the most
      common surgical complication.

PMID- 27712894
TI  - Rib Fibrous Dysplasia Mimicking Extrapleural Hematoma.

PMID- 27712892
TI  - Inspissated bile syndrome; Safe and effective minimally invasive treatment with
      percutaneous cholecystostomy in neonates and infants.
AB  - PURPOSE: Inspissated bile syndrome (IBS) is a rare cause of obstructive jaundice
      in neonates and infants with several treatment options reported. We present our
      experience with the use of minimally invasive ultrasound-guided percutaneous
      cholecystostomy drain catheter placement with ongoing saline lavage in neonates
      and infants. METHODS: Retrospective chart review of patients treated with
      percutaneous cholecystostomy, from February 2010 till June 2015. We reviewed the
      technical and clinical success along with complications of the procedure.
      RESULTS: There were 6 patients, mean age 17weeks (range 4-40). Most had
      significant risk factors for IBS presenting with biliary obstruction. A total of
      7 procedures performed on the 6 patients, with a technical success rate of 6/7.
      One patient required cannulation of the intrahepatic biliary system. Drains were
      flushed for a median of 26days (10-70). Clinical success was achieved in all
      patients. 3 had displacement of the drain, one of which required re-insertion.
      Another developed a small sub-hepatic collection post procedure with pyrexia. On
      long term follow up one was found to have a forme fruste choledochal cyst.
      CONCLUSION: Centers with suitable interventional radiology services ultrasound
      guided percutaneous cholecystostomy drain catheter placement with ongoing saline
      lavage is a safe and effective minimally invasive treatment for IBS in neonates
      and infants.

PMID- 27712893
TI  - Two years in IGF research.
AB  - The last two years of insulin-like growth factor (IGF) research has yielded a
      vast literature highlighting the central role IGFs factors play in processes such
      as development, growth, aging and neurological function. It also provides our
      latest understanding of how IGF system perturbation is linked to diseases
      including growth deficiency, cancer, and neurological and cardiovascular
      diseases. A snapshot of the highlights is presented in this review, focussing on
      the topics of IGFs and growth, comparative and structural biology to understand
      insulin-like peptide function, IGFs and cancer, and IGFs and neurological
      function. New revelations in the IGF field include the unexpected discovery that
      the gut microbiome has a remarkable influence on the GH/IGF axis to influence
      growth, that the insulin of cone snails provides novel insight into the mechanism
      of receptor binding, and that macrophages in the tumour microenvironment can
      provide IGF-I to promote drug resistance. These advances and many others provide
      the exciting basis for future development of disease treatments and for
      biomarkers of disease.

PMID- 27712895
TI  - Osteochondroma.

PMID- 27712896
TI  - Choroid Detachment, a Rare Cause of Vision Loss Diagnosed by Point-of-Care
      Ultrasound.
AB  - BACKGROUND: Choroid detachment is a rare disease process that has a multitude of
      etiologies; usually related to recent ophthalmological surgery, eye trauma,
      corneal ulcers, or intraocular pressure-lowering agents. Point-of-care ocular
      ultrasound has high utility and accuracy in diagnosing pathology of the eye. CASE
      REPORT: We present a case of a patient who presented with vision loss caused by a
      choroid detachment diagnosed on point-of-care ultrasound because fundoscopic
      examination was limited due to cataracts. Ultrasound findings based on location
      and appearance during both static and dynamic evaluation that help differentiate
      a choroid vs. a retinal detachment are also described. WHY SHOULD AN EMERGENCY
      PHYSICIAN BE AWARE OF THIS?: Choroid detachments have a different sonographic
      appearance, as well as management, compared to a retinal detachment.

PMID- 27712899
TI  - Response.

PMID- 27712897
TI  - A Rare But Important Entity: Epistaxis in Infants.
AB  - BACKGROUND: Epistaxis is a common emergency department (ED) complaint; however,
      this entity is rare among children younger than 2 years of age. In this age
      group, epistaxis may be a presenting sign of a bleeding disorder or nonaccidental
      trauma. CASE REPORT: We present a case of a 2-month-old infant who was evaluated
      in the pediatric ED for epistaxis and discharged home. The infant returned 2 days
      later with facial swelling and irritability, and was found to have significant
      head trauma. In this article we review the epidemiology and differential
      diagnoses for epistaxis among infants, as well as the initial approach to the
      evaluation of this uncommon clinical entity in this age group. WHY SHOULD AN
      EMERGENCY PHYSICIAN BE AWARE OF THIS?: Potential etiologies for epistaxis among
      infants and young children include severe systemic disease and nonaccidental
      trauma. Given its rarity and possible clinical significance, the approach to
      epistaxis differs in this age group. Emergency physicians should screen for and
      exclude a bleeding disorder while also having a very low threshold for a
      nonaccidental trauma evaluation.

PMID- 27712898
TI  - Lung Ultrasound Diagnosis of Pneumothorax and Intervention: The Fundamental Role
      of Clinical Data.

PMID- 27712900
TI  - Graveyard Electrocardiogram.

PMID- 27712901
TI  - Electronic Cigarette Explosion Resulting in a C1 and C2 Fracture: A Case Report.
AB  - BACKGROUND: Electronic cigarettes have seen a drastic increase in use. A lithium
      ion battery is often used as the rechargeable battery of the electronic cigarette
      device and has recently received much attention in terms of safety. There are
      several recent case reports in the scientific literature of injuries due to
      electronic cigarette explosions that involved soft-tissue injuries. CASE REPORT:
      We report a significant spinal fracture from an electronic-cigarette explosion in
      a 27-year-old male. The electronic cigarette exploded during use, sending the
      mouthpiece through the pharynx and into the first cervical vertebra and resulting
      in fractures of the first and second vertebrae. An x-ray study of the neck showed
      a foreign body in the neck at the level of C1. A computed tomography scan of the
      neck showed fractures of C1. The foreign body was removed in the operating room.
      The patient was discharged home without neurologic sequelae. WHY SHOULD AN
      EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case report is the first case of a
      cervical spine injury due to the explosion of an electronic cigarette. This case
      demonstrates that an electronic cigarette explosion can cause potentially serious
      penetrating neck injury. Emergency physicians should be aware of the potential
      danger of electronic cigarettes and have a low threshold to obtain radiographic
      tests and surgical consultation in the case of electronic cigarette explosion in
      the oral cavity. As the use of electronic cigarettes continue to increase, it is
      likely that injuries associated with them will also increase.

PMID- 27712902
TI  - Response to Letter to the Editor.

PMID- 27712905
TI  - Whole-breast US following mammography and breast MRI in newly diagnosed breast
      cancer patients: can it be more than just a guidance tool for biopsy?
AB  - AIM: To evaluate the role of ultrasound (US) following magnetic resonance imaging
      (MRI) and mammography in patients with newly diagnosed breast cancers by
      assessing the additional cancer detection rate of US. MATERIAL AND METHODS: Two
      hundred and twenty-five women who had undergone 225 MRI examinations followed by
      US were included. An US-detected additional cancer was defined as a lesion
      detected using breast US that had not been detected by MRI, and which was shown
      to be malignant at histopathology. The rate of additional cancer detection,
      incidence of additional malignancies, positive predictive value (PPV), and false
      positive (FP) rate were analysed. Factors associated with an increase in the
      additional cancer detection rate were analysed. RESULTS: The additional cancer
      detection rate was 0% (0/225) for the ipsilateral breast and 0.9% (2/225) for the
      contralateral breast, and the PPVs were 0% (0/5) and 100% (2/2), respectively.
      The overall TP:FP ratio was 0.4 (2:5). The additional cancer detection rate was
      higher for cases with moderate and severe background parenchymal enhancement than
      cases with minimal and mild background parenchymal enhancement (p=0.003). The
      additional cancer detection rate for cases with moderate and severe background
      parenchymal enhancement was 5.7% (2/35) for the contralateral breast (p=0.003).
      CONCLUSION: Preoperative breast US following MRI and mammography can help
      clinicians screen for contralateral cancers with an additional detection rate of
      0.9%. Moreover, whole-breast US might be a useful contralateral screening
      modality in cases with moderate or marked parenchymal enhancement on breast MRI.

PMID- 27712903
TI  - End-tidal CO2 on admission is associated with hemorrhagic shock and predicts the
      need for massive transfusion as defined by the critical administration threshold:
      A pilot study.
AB  - BACKGROUND: Critical administration threshold (>=3 units of packed red blood
      cells/h or CAT+) has been proposed as a new definition for massive transfusion
      (MT) that includes volume and rate of blood transfusion. CAT+ has been shown to
      eliminate survivor bias and be a better predictor of mortality than the
      traditional MT (>10 units/24h). End-tidal CO2 (ET CO2) negatively correlates with
      lactate and is an early predictor of shock in trauma patients. We conducted a
      pilot study to test the hypothesis that low ET CO2 on admission predicts CAT+.
      METHODS: ET CO2 via capnography and serum lactate were prospectively collected on
      admission for 131 patients requiring trauma team activation. Demographic data
      were obtained from patient charts. Excluded were patients with isolated head
      injuries, traumatic arrests, or pre-hospital intubations. CAT+/- status was
      determined for each hour up to 6h from admission as described; likewise, MT+/-
      status was determined up to 24h from admission. RESULTS: After exclusion
      criteria, 67 patients were analyzed. Mean age was 41.2 (SD 18.5). Thirty-three
      patients had a blunt mechanism of injury (49%), median ISS was 9 (interquartile
      range 4-19), and there were 6 deaths (9%). ET CO2 and lactate were negatively
      correlated by Spearman rank-based correlation (rho=-0.41, p=0.0006). Twenty-one
      (31%) and 8 (12%) patients were CAT+ and traditional MT+, respectively. There
      were a significantly greater proportion of patients with ISS>15, ET CO2 <35, or
      who died found to be CAT+. A binomial logistic regression model adjusting for
      age, SBP <90, HR, and ISS >15 revealed ET CO2 < 35 to be independently predictive
      of CAT+ (OR 9.24, 95% CI 1.51-56.57, p=0.016). CONCLUSIONS: This pilot study
      demonstrated that low ET CO2 had strong association with standard indicators for
      shock and was predictive of patients meeting CAT+ criteria in the first 6h after
      admission. Further study to verify these results and to elucidate CAT criteria's
      association with mortality will require a larger sample size.

PMID- 27712904
TI  - Factors affecting planned return to work after trauma: A prospective descriptive
      qualitative and quantitative study.
AB  - The use of patient reported outcome measures (PROMs) in trauma is limited. The
      aim of this pilot study is to evaluate qualitative responses and factors
      affecting planned return to work following significant trauma, for which there is
      currently a poor evidence base. National ethical approval was obtained for
      routine prospective PROMs data collection, including EQ-5D, between Sept 2013 and
      March 2015 for trauma patients admitted to the Sussex Major Trauma Centre (n=92).
      84 trauma patients disclosed their intended return to work at discharge.
      Additional open questions asked 'things done well' and 'things to be improved'.
      EQ-5D responses were valued using the time trade-off method. Statistical analysis
      between multiple variables was completed by ANOVA, and with categorical
      categories by Chi squared analysis. Only 18/68 of patients working at admission
      anticipated returning to work within 14days post-discharge. The injury severity
      scores (ISS) of those predicting return to work within two weeks and those
      predicting return to work longer than two weeks were 14.17 and 13.59,
      respectively. Increased physicality of work showed a trend towards poorer return
      to work outcomes, although non-significant in Chi-squared test in groups
      predicting return in less than or greater than two weeks (4.621, p=0.2017ns). No
      significant difference was demonstrated in the comparative incomes of patients
      with different estimated return to work outcomes (ANOVA r2=0.001, P=0.9590ns). EQ
      5D scores were higher in those predicting return to work within two weeks when
      compared to greater than two weeks. Qualitative thematic content analysis of open
      responses was possible for 66/92 of respondents. Prominent positive themes were:
      care, staff, professionalism, and communication. Prominent negative themes were:
      food, ward response time, and communication. This pilot study highlights the
      importance of qualitative PROMs analysis in leading patient-driven improvements
      in trauma care. We provide standard deviations for ISS scores and EQ-5D scores in
      our general trauma cohort, for use in sample size calculations for further
      studies analysing factors affecting return to work after trauma.

PMID- 27712906
TI  - Distribution of intravoxel incoherent motion MRI-related parameters in the brain:
      evidence of interhemispheric asymmetry.
AB  - AIM: To compare intravoxel incoherent motion (IVIM) magnetic resonance imaging
      (MRI)-derived true diffusion (D) and perfusion fraction (f)-values of the two
      hemispheres to detect the presence of asymmetrical differences. MATERIALS AND
      METHODS: Forty-seven healthy right-handed volunteers were assessed using IVIM
      imaging. The interhemispheric D- and f-values were compared using paired t-tests
      and two related-samples Wilcoxon's test. RESULTS: Comparison of the
      interhemispheric D- and f-values of the grey matter revealed a significant
      difference in the D-value of the frontal lobe and the f-value of the temporal
      lobe (p=0.028, p=0.030, respectively). A significant difference in the D-values
      of the frontal, temporal, and occipital lobes (p=0.003, p=0.005, and p=0.001,
      respectively) was seen, whereas no significant difference in f-values was seen.
      CONCLUSIONS: The distribution of the IVIM-derived D- and f-values in the two
      hemispheres was not completely symmetrical. Radiologists should consider this
      difference when the contralateral region is used as internal reference to
      normalise the IVIM imaging results. Average values of the interhemispheric white
      matter within the same lobe as the lesion may be the best internal reference.

PMID- 27712907
TI  - Classic signs in head and neck imaging.
AB  - Radiologists have long relied upon the use of metaphoric imaging signs to
      attribute meaning to disease or anatomy-specific imaging patterns encountered in
      clinical imaging. Teachers of radiology often employ the use of such signs to
      help learners rapidly identify the typical appearance of various pathologies.
      Head and neck (H&N) imaging is no exception, and as a specialty that deals with
      uncommon pathologies and complex anatomy, learners and practising radiologists
      alike may benefit from this simplistic, pattern-based approach. In this review,
      we present a compendium of classic imaging signs of H&N lesions, including signs
      related to traumatic, infectious, neoplastic, congenital, and inflammatory
      aetiologies found throughout the spectrum of H&N sites (temporal bones, orbits,
      paranasal sinuses, larynx, salivary glands, and neck soft tissues). Additionally,
      we identify potential pitfalls and detail critical clinical ramifications related
      to the rapid and accurate diagnosis of these pathologies.

PMID- 27712909
TI  - Evolution of the electrocardiogram in a patient with arrhythmogenic right
      ventricular cardiomyopathy.

PMID- 27712908
TI  - How to improve the diagnosis of eosinophilic esophagitis: Experience from a case
      series in Mexico.
AB  - INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, immune disorder
      mediated largely by food antigens. It shares nonspecific symptoms with
      gastroesophageal reflux disease (GERD). EoE is rarely reported in Mexico, perhaps
      due to the racial characteristics of the population or because of insufficient
      diagnostic suspicion. AIMS: Our aim was to describe a Mexican cohort with EoE and
      evaluate the usefulness of the clinical history and endoscopy in the EoE
      diagnosis, in comparison with GERD patients. MATERIALS AND METHODS: A
      retrospective study was carried out on the clinical characteristics and
      endoscopic and histopathologic findings in patients with EoE, along with a case
      control study on patients with GERD. The endoscopic images obtained were
      interpreted in a blind and randomized manner by 4 gastroenterologists, before and
      after providing them with information on the characteristic alterations of EoE.
      The esophageal biopsies were also blinded to 2 pathologists that evaluated their
      diagnostic correlation. The Fisher's exact test and Mann-Whitney U test were used
      in the statistical analysis. RESULTS: Fourteen patients with EoE were included in
      the study. Ten (71%) of them were men and the mean age of the patients was 35
      years. There were more subjects with a personal history of asthma (p=0.0023) and
      food impaction (p=0.04) in the EoE group. The initial evaluation of the
      endoscopic findings showed 53% correct EoE interpretations and rose to 96% in the
      second revision (sensitivity 100%, specificity 71%, PPV 65%, NPV 100%).
      CONCLUSIONS: Mexican patients with EoE have similar characteristics to those of
      patients in western case series. Clinical awareness of the disorder increases
      endoscopic diagnosis in up to 40% of cases.

PMID- 27712910
TI  - Health-Related Quality of Life after Coronary Revascularization: A systematic
      review with meta-analysis.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis to summarize evidence
      and determine the impact of coronary revascularization (CR) on cardiac patients'
      Health-Related Quality of Life (HRQoL), highlighting factors that may affect this
      outcome in patients. METHODS: A systematic search of Medline (Pubmed), EMBASE,
      Cochrane Library, Sciverse (Science Direct and Scopus) and PsycInfo was conducted
      to identify studies published from January 2000 to December 2012. Data were
      analyzed using MIX 2.0 Pro and SPSS 20. RESULTS: Thirty-four longitudinal studies
      met the inclusion criteria; these studies included 15,992 patients, of whom 8,027
      had undergone PCI, 6,348 had undergone CABG and 1,617 had received medication
      treatment. Moderate long-term effect sizes were revealed for both CR procedures.
      Both percutaneous coronary interventions (PCI) and coronary artery bypass graft
      surgery (CABG) had significantly greater effects on HRQoL than did medication;
      however, the CR procedures did not differ significantly from each other.
      Moderators included the type of instrument used to assess HRQoL and the study
      quality. Benefits related to physical functioning were greater than those related
      to psychosocial functioning in patients treated with CABG. CONCLUSIONS: Empirical
      research highlights the positive effect of CR on patient HRQoL. Researchers
      should carefully select the instrument they use to measure HRQoL, as this may
      affect the results and thus conclusions. More RCTs and between-group studies
      employing pre-post designs should be conducted before clear conclusions can be
      drawn.

PMID- 27712911
TI  - Ulnar artery: The Ulysses ultimate resort for coronary procedures.
AB  - Despite the increasing worldwide adoption of the transradial access site, the
      ulnar artery (UA) only very infrequently serves as a primary option for coronary
      procedures. In contrast to the uncertainty surrounding previous reports regarding
      the feasibility and safety, recent data from larger registries and randomized
      trials provide more conclusive evidence that the transulnar route may be safely
      selected as an alternative arterial access approach. However, a default
      transulnar strategy appears time-consuming and is associated with higher
      crossover rates compared with the radial artery (RA). Once arterial access is
      obtained, the likelihood of a successful coronary procedure is high and similar
      between the two forearm arteries. The UA has similar flow-mediating vasodilating
      properties with and seems at least as vulnerable as the RA with regard to
      incident occlusion, with UA occlusion (UAO) rates being probably higher than
      previously anticipated. A learning curve effect may not be apparent for crossover
      rates among experienced radialists, but increasing experience is associated with
      reduction in the fluoroscopy time, contrast volume and frequency of large
      hematoma formation. The UA may represents an important alternative access site
      for coronary procedures, and experienced radial operators should obtain
      additional skills to perform the transulnar approach. Nevertheless, in view of
      this method's lower feasibility compared to the RA, an initial ulnar access
      strategy should be reserved for carefully selected patients to ensure
      satisfactory cannulation rates.

PMID- 27712913
TI  - [Comment on "Introduction of the photoselective vaporization of the prostate in
      an outpatient setting: Outcomes after the first 100 cases"].

PMID- 27712912
TI  - [Local analgesia during flexible cystoscopy in male patients: A non-inferiority
      study comparing Xylocaine(r) gel to Instillagel(r) Lido].
AB  - INTRODUCTION: Local anesthesia using urethral gel has been proven to reduce
      discomfort of male patients during flexible cystoscopy. This study was a non
      inferiority study between two lidocain-containing urethral gel (Instillagel(r)
      Lido and Xylocaine(r) gel). METHODS: A prospective single center study was
      conducted between June 2014 and November 2014. Male patients seen in the office
      and in whom a flexible cystoscopy was planned were included in the present study
      and received urethral instillation of either Xylocaine(r) gel or Instillagel(r)
      Lido at least 5minutes before flexible cystoscopy. No other anesthetic agent was
      used. Primary endpoint was pain during the procedure, assessed through visual
      analog scale (VAS) from 0 to 10. RESULTS: Four hundred and sixty-one men were
      included: 233 in the Instillagel(r) Lido group and 228 in the Xylocaine(r) gel
      group. Indications of flexible cystoscopy non-muscle invasive bladder cancer
      follow-up in 44 % of cases, hematuria work-up in 21 % of cases and lower urinary
      tract symptoms work-up in 35 %. Patients' age was comparable betwwen both groups:
      64.5 years (+/-1.1) in the Instillagel(r) Lido group and 66.2 years (+/-1.1) in
      the Xylocaine(r) gel group (P=0.29). The mean VAS was 0.8 (+/-0.1) in the
      Instillagel(r) Lido group and 0.6 (+/-0.1) in the Xylocaine(r) gel group
      (P=0.10). The non-inferiority criterion was reached (P<0.001) as the average
      difference in VAS between the two groups was 0.2 with a confidence interval not
      comprising 1 (CI 97.5 %: -0.47; 0.07). CONCLUSION: In this prospective study,
      Instillagel(r) Lido was not inferior to Xylocaine(r) gel for local analgesia
      during flexible cystoscopy in male patients. LEVEL OF EVIDENCE: 4.

PMID- 27712914
TI  - [Intravesical instillations in non-muscle-invasive bladder cancer (NMIBC).
      Prospects for thermochemotherapy].
AB  - : Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high risk of
      recurrence when performing only a transurethral resection of the bladder (TURB).
      Intravesical instillations are performed postoperatively to decrease the rate of
      recurrence. The standard agents currently used are Mitomycin-C (MMC) or bacillus
      Calmette-Guerin (BCG). In order to further enhance the efficacy of the adjuvant
      treatments and/or diminish their side effects, alternative treatments are
      studied. Intravesical MMC combined with hyperthermia could be an interesting
      alternative active treatment for intermediate- and possibly high-risk NMIBC, and
      has been investigated in the past years. Two methods for achieving hyperthermia
      are described and presently evaluated: heating the bladder wall by the mean of an
      intravesical microwave generator (Synergo(r)) and heating the MMC before it is
      instilled in the bladder (Combat BRS(r)). LEVEL OF EVIDENCE: 5.

PMID- 27712915
TI  - Comparative genomics unravels metabolic differences at the species and/or strain
      level and extremely acidic environmental adaptation of ten bacteria belonging to
      the genus Acidithiobacillus.
AB  - Members of the Acidithiobacillus genus are widely found in extreme environments
      characterized by low pH and high concentrations of toxic substances, thus it is
      necessary to identify the cellular mechanisms needed to cope with these harsh
      conditions. Pan-genome analysis of ten bacteria belonging to the genus
      Acidithiobacillus suggested the existence of core genome, most of which were
      assigned to the metabolism-associated genes. Additionally, the unique genes of
      Acidithiobacillus ferrooxidans were much less than those of other species. A
      large proportion of Acidithiobacillus ferrivorans-specific genes were mapped
      especially to metabolism-related genes, indicating that diverse metabolic
      pathways might confer an advantage for adaptation to local environmental
      conditions. Analyses of functional metabolisms revealed the differences of carbon
      metabolism, nitrogen metabolism, and sulfur metabolism at the species and/or
      strain level. The findings also showed that Acidithiobacillus spp. harbored
      specific adaptive mechanisms for thriving under extreme environments. The genus
      Acidithiobacillus had the genetic potential to resist and metabolize toxic
      substances such as heavy metals and organic solvents. Comparison across species
      and/or strains of Acidithiobacillus populations provided a deeper appreciation of
      metabolic differences and environmental adaptation, as well as highlighting the
      importance of cellular mechanisms that maintain the basal physiological functions
      under complex acidic environmental conditions.

PMID- 27712917
TI  - Postoperative (Chemo)Radiotherapy for Oral Cavity Squamous Cell Carcinomas:
      Outcomes and Patterns of Failure.
AB  - AIMS: To determine outcomes after adjuvant radiotherapy for squamous cell
      carcinoma of the oral cavity and to correlate locoregional recurrence patterns
      with radiotherapy target volumes. MATERIALS AND METHODS: All patients receiving
      adjuvant radiotherapy+/-chemotherapy after surgery with curative intent for oral
      cavity squamous cell carcinoma between 2007 and 2012 were retrospectively
      analysed. Locoregional recurrences were reconstructed on the planning computed
      tomography scan by both deformable image co-registration and by visual
      assessment. Recurrences were categorised as in-field, marginal or out-of-field if
      >95%, 20-95%, and <20% of the recurrence volume was encompassed by 95% of the
      prescription isodose, respectively. RESULTS: In total, 106 patients with a median
      follow-up of 42 months were included. Oral cavity subsites included oral tongue
      (54%) and floor of mouth (32%). Thirty (28%) patients received concurrent
      chemotherapy. Fifty-five (52%) patients received bilateral neck radiotherapy. Two
      year overall, disease-free, local disease-free, regional disease-free and distant
      metastases-free survival were 72, 83, 92, 89, 94%, respectively. On multivariate
      analysis, extracapsular nodal spread was the only factor significantly associated
      with inferior overall survival. Fourteen (13%) patients have experienced
      locoregional failure. Of the eight local recurrences at the primary tumour site,
      four, three and one were classified as in-field, marginal and out-of-field,
      respectively. Of 10 regional recurrences, one, one and eight were in-field,
      marginal and out-of-field. There were 7/21 (33%) contralateral regional
      recurrences in patients with pN2a/b disease who did not receive contralateral
      neck irradiation; there were 0/21 (0%) and 0/9 (0%) contralateral regional
      recurrences in patients with pN0 or pN1 disease, respectively, who did not
      receive contralateral neck irradiation. CONCLUSION: Marginal recurrences
      highlight the need for generous target volume delineation. Based upon rates of
      contralateral regional recurrences, a comprehensive approach to target volume
      selection should be advised for tumour subsites with bilateral lymphatic drainage
      in the presence of pN2a/b disease.

PMID- 27712916
TI  - Mesorhizobium olivaresii sp. nov. isolated from Lotus corniculatus nodules.
AB  - In this study four Mesorhizobium strains isolated from Lotus corniculatus nodules
      in Granada (Spain) were characterized. Their 16S rRNA gene sequences were closely
      related to those of M. albiziae LMG 23507T and M. chacoense Pr5T showing 99.4 and
      99.2% similarity values, respectively. The analysis of concatenated rpoB, recA,
      atpD and glnII genes showed they formed a cluster with internal similarities
      higher than 97%. The closest species also were M. albiziae LMG 23507T and M.
      chacoense Pr5T showing similarity values lower than 92% in rpoB, recA and glnII
      genes and lower than 96.5% in the atpD gene. These results indicated that the L.
      corniculatus strains belong to a new species of genus Mesorhizobium which was
      confirmed by DNA-DNA hybridization and phenotypic characterization. Therefore a
      new species with the name Mesorhizobium olivaresii sp. nov. is proposed, and the
      type strain is CPS13T (LMG 29295T=CECT 9099T).

PMID- 27712918
TI  - Enrichment and characterization of acid-tolerant nitrifying sludge.
AB  - Nitrification is an acidifying process that requires the addition of external
      alkalinity because of the alkaliphilic nature of the most ammonia-oxidizing
      bacteria. In this study, aerobic activated sludge was used as inoculum in an
      internal loop air-lift reactor, which resulted in successful enrichment of acid
      tolerant nitrifying (ACIN) sludge at pH 6.0 by sequential addition of tea orchard
      soil suspension. The results showed that ACIN sludge had a remarkable acid
      tolerant capability with a volumetric ammonia conversion rate of 1.13 kg N m-3
      day-1. ACIN sludge showed a higher maximum specific ammonia conversion rate (0.29
      g N g-1 VSS day-1) than neutrophilic nitrifying sludge (0.14 g N g-1 VSS day-1)
      at pH 6.0 and had good resistance against pH fluctuations, with a maximum
      specific ammonia conversion rate (0.584 g N g-1 VSS day-1) at pH 7.5. Microbial
      community analysis indicated that the higher abundance of acid tolerant
      Nitrosospira and ammonia-oxidizing archaea laid a solid foundation for the
      remarkable acid-tolerant capability of ACIN sludge.

PMID- 27712919
TI  - Greening Drylands with Seawater Easily and Naturally.
AB  - The sun and sea are inexhaustible sources of energy and water that could be used
      to transform drylands into more viable ecosystems. A sustainable and cost
      effective approach is proposed for greening drylands and restoring wildlife and
      biodiversity in deserts using seawater desert-houses (or movable seawater ponds)
      that could offer important environmental advantages.

PMID- 27712920
TI  - Using Prokaryotes for Carbon Capture Storage.
AB  - Geological storage of CO2 is a fast-developing technology that can mitigate
      rising carbon emissions. However, there are environmental concerns with the long
      term storage and implications of a leak from a carbon capture storage (CCS) site.
      Traditional monitoring lacks clear protocols and relies heavily on physical
      methods. Here, we discuss the potential of biotechnology, focusing on microbes
      with a natural ability to utilize and assimilate CO2 through different metabolic
      pathways. We propose the use of natural microbial communities for CCS monitoring
      and CO2 utilization, and, with examples, demonstrate how synthetic biology may
      maximize CO2 uptake within and above storage sites. An integrated physical and
      biological approach, combined with metagenomics data and biotechnological
      advances, will enhance CO2 sequestration and prevent large-scale leakages.

PMID- 27712922
TI  - Corrigendum to "Impaired motor preparation and execution during standing reach in
      people with chronic stroke" [Neurosci. Lett. 630 (2016) 38-44].

PMID- 27712921
TI  - Does physiological response to disease incur cost to reproductive ecology in a
      sexually dichromatic amphibian species?
AB  - It is well known that the disease chytridiomycosis, caused by the fungal pathogen
      Batrachochytrium dendrobatidis (Bd) has contributed to amphibian declines
      worldwide. The impact of Bd varies, with some species being more susceptible to
      infection than others. Recent evidence has shown that Bd can have sub-lethal
      effects, whereby increases in stress hormones have been associated with
      infection. Could this increased stress response, which is a physiological
      adaptation that provides an increased resilience against Bd infection,
      potentially be a trade-off with important life-history traits such as
      reproduction? We studied this question in adult male frogs of a non-declining
      species (Litoria wilcoxii). Frogs were sampled for (1) seasonal hormone
      (testosterone and corticosterone), color and disease profiles, (2) the
      relationship between disease infection status and hormone levels or dorsal color,
      (3) subclinical effects of Bd by investigating disease load and hormone level,
      and (4) reproductive and stress hormone relationships independent of disease.
      Testosterone levels and color score varied seasonally (throughout the
      spring/summer months) while corticosterone levels remained stable. Frogs with
      high Bd prevalence had significantly higher corticosterone levels and lower
      testosterone levels compared to uninfected frogs, and no differences in color
      were observed. There was a significant positive correlation between disease load
      and corticosterone levels, and a significant negative relationship between
      disease load and testosterone. Our field data provides novel evidence that
      increased physiological stress response associated with Bd infection in wild
      frogs, could suppress reproduction by down-regulating gonadal hormones in
      amphibians, however the impacts on reproductive output is yet to be established.

PMID- 27712924
TI  - Testosterone administration does not affect men's rejections of low ultimatum
      game offers or aggressive mood.
AB  - Correlative evidence suggests that testosterone promotes dominance and
      aggression. However, causal evidence is scarce and offers mixed results. To
      investigate this relationship, we administered testosterone for 48h to 41 healthy
      young adult men in a within-subjects, double-blind placebo-controlled balanced
      crossover design. Subjects played the role of responders in an ultimatum game,
      where rejecting a low offer is costly, but serves to destroy the proposer's
      profit. Such action can hence be interpreted as non-physical aggression in
      response to social provocation. In addition, subjects completed a self-assessed
      mood questionnaire. As expected, self-reported aggressiveness was a key predictor
      of ultimatum game rejections. However, while testosterone affected subjective
      ratings of feeling energetic and interested, our evidence strongly suggests that
      testosterone had no effect on ultimatum game rejections or on aggressive mood.
      Our findings illustrate the importance of using causal interventions to assess
      correlative evidence.

PMID- 27712923
TI  - Echo Decorrelation Imaging of Rabbit Liver and VX2 Tumor during In Vivo
      Ultrasound Ablation.
AB  - In open surgical procedures, image-ablate ultrasound arrays performed thermal
      ablation and imaging on rabbit liver lobes with implanted VX2 tumor. Treatments
      included unfocused (bulk ultrasound ablation, N = 10) and focused (high-intensity
      focused ultrasound ablation, N = 13) exposure conditions. Echo decorrelation and
      integrated backscatter images were formed from pulse-echo data recorded during
      rest periods after each therapy pulse. Echo decorrelation images were corrected
      for artifacts using decorrelation measured prior to ablation. Ablation prediction
      performance was assessed using receiver operating characteristic curves. Results
      revealed significantly increased echo decorrelation and integrated backscatter in
      both ablated liver and ablated tumor relative to unablated tissue, with larger
      differences observed in liver than in tumor. For receiver operating
      characteristic curves computed from all ablation exposures, both echo
      decorrelation and integrated backscatter predicted liver and tumor ablation with
      statistically significant success, and echo decorrelation was significantly
      better as a predictor of liver ablation. These results indicate echo
      decorrelation imaging is a successful predictor of local thermal ablation in both
      normal liver and tumor tissue, with potential for real-time therapy monitoring.

PMID- 27712925
TI  - Serotonin 1A agonism decreases affiliative behavior in pair-bonded titi monkeys.
AB  - Relatively little is known about serotonergic involvement in pair-bonding despite
      its putative role in regulating social behavior. Here we sought to determine if
      pharmacological elevation of serotonin 1A (5-HT1A) receptor activity would lead
      to changes in social behavior in pair-bonded male titi monkeys (Callicebus
      cupreus). Adult males in established heterosexual pairs were injected daily with
      the selective 5-HT1A agonist 8-OH-DPAT or saline for 15days using a within
      subjects design. Social behavior with the female pair-mate was quantified, and
      plasma concentrations of oxytocin, vasopressin, and cortisol were measured. When
      treated with saline, subjects showed reduced plasma oxytocin concentrations,
      while 8-OH-DPAT treatment buffered this decrease. Treatment with 8-OH-DPAT also
      led to decreased plasma cortisol 15minutes post-injection and decreased social
      behavior directed toward the pair-mate including approaching, initiating contact,
      lipsmacking, and grooming. The reduction in affiliative behavior seen with
      increased activity at 5-HT1A receptors indicates a substantial role of serotonin
      activity in the expression of social behavior. In addition, results indicate that
      the effects of 5-HT1A agonism on social behavior in adulthood differ between
      rodents and primates.

PMID- 27712926
TI  - Species and emm-type distribution of group C and G streptococci from different
      sites of isolation.
AB  - beta-Haemolytic streptococci of groups C (GCS) and G (GGS) from human infections
      typically belong to Streptococcus dysgalactiae and are important human pathogens.
      Among GGS (183 isolates), several emm-types were identified without significant
      differences between different sites of isolation. For GCS (79 isolates), the type
      distribution was markedly different and more restricted.

PMID- 27712927
TI  - Gut eradication of VIM-1 producing ST9 Klebsiella oxytoca after fecal microbiota
      transplantation for diarrhea caused by a Clostridium difficile hypervirulent R027
      strain.
AB  - We report the fecal carriage eradication of a VIM-1-producing ST9 Klebsiella
      oxytoca strain in a pluripathological 84-year-old woman after fecal microbiota
      transplantation to control relapsing R027 hypervirulent Clostridium difficile
      infections. The donor was her son, in which the absence of fecal carbapenemase
      producing bacteria was corroborated.

PMID- 27712928
TI  - Colistin enhances therapeutic efficacy of daptomycin or teicoplanin in a murine
      model of multiresistant Acinetobacter baumannii sepsis.
AB  - We investigated the efficacy of colistin combined with teicoplanin or daptomycin
      in an experimental mouse model of multiresistant Acinetobacter baumannii
      infection. Animal received intraperitoneally 1ml saline containing 2*1010CFU of
      A. baumannii. Colistin, daptomycin, teicoplanin, and colistin plus daptomycin or
      teicoplanin were given by intraperitoneal administration 2h after bacterial
      challenge. A control group received sodium chloride solution. In the in vitro
      study A. baumannii showed to be susceptible only to colistin with MIC of 2mg/l.
      In the in vivo study, colistin alone showed a good antimicrobial efficacy. When
      combined with teicoplanin or daptomycin, colistin produced the lowest bacterial
      and the best survival rates. In immunological studies, when colistin was
      associated to daptomycin or teicoplanin, both the number and the cytotoxic
      activity of NK cells increased. In conclusion, colistin combined with teicoplanin
      or daptomycin may improve the therapy of multiresistant A. baumannii infection.

PMID- 27712929
TI  - Early detection of OXA-370-producing Klebsiella pneumoniae ST17 co-harboring
      blaCTX-M-8 in Brazil.
AB  - We aimed to describe an early detection of OXA-370-producing Klebsiella
      pneumoniae in Brazil. The isolate CCBH10079 belonged to ST17 and the blaOXA-370
      was located in a plasmid of ?57kb.

PMID- 27712930
TI  - Type 4 cardiorenal syndrome.
AB  - The Acute Dialysis Quality Initiative consensus conference proposed a
      classification of cardiorenal syndrome (CRS), aiming for a better delineation of
      each subtype. Although the exact pathophysiology of type 4 CRS is not completely
      understood, the mechanisms involved are probably multifactorial. There is growing
      evidence that oxidative stress is a major connector in the development and
      progression of type 4 CRS. Giving its complexity, poor prognosis and increasing
      incidence, type 4 CRS is becoming a significant public health problem. Patients
      with chronic kidney disease are particularly predisposed to cardiac dysfunction,
      due to the high prevalence of traditional cardiovascular risk factors in this
      population, but the contribution of risk factors specific to chronic kidney
      disease should also be taken into account. Much remains to be elucidated about
      type 4 CRS: despite progress over the last decade, there are still significant
      questions regarding its pathophysiology and there is as yet no specific therapy.
      A better understanding of the mechanisms involved may provide potential targets
      for intervention. The present review will provide a brief description of the
      definition, epidemiology, diagnosis, prognosis, biomarkers and management
      strategies of type 4 CRS, and the pathophysiological mechanisms and risk factors
      presumably involved in its development will be particularly highlighted.

PMID- 27712931
TI  - Uncommonly reported effects of methamphetamine.

PMID- 27712932
TI  - Comparison of cardiovascular responses after injection of lidocaine with either
      clonidine or adrenaline: a two-year comparative analysis.
AB  - Our aim was to evaluate the efficacy of clonidine with lidocaine as a local
      anaesthetic agent for inferior alveolar mandibular nerve blocks for dental
      extraction. We studied 200 patients who required extraction of mandibular teeth
      and divided them into two groups of 100 each, the first of which was given
      lidocaine and adrenaline (12.5MUg/ml) and the second lidocaine and clonidine
      (15MUg/ml). Cardiovascular vascular variables (blood pressure, heart rate, and
      mean arterial pressure) were assessed before, during, and after extraction, and
      postoperative pain was measured on a visual analogue scale. There was a
      significant reduction in systolic blood pressure (p=0.0001) and heart rate
      (p=0.000) after injection of clonidine. However, they both increased after
      injections of lidocaine plus adrenaline, and there was a significant reduction in
      pain at four hours postoperatively with clonidine (p=0.000). Our results showed
      that anaesthesia with lidocaine and clonidine decreases systolic blood pressure
      and heart rate 10minutes after injection for extraction of lower mandibular
      teeth. We suggest that patients who have local anaesthetic with lidocaine and
      clonidine are at minimal cardiovascular risk and there is no difference in the
      onset of anaesthesia.

PMID- 27712933
TI  - [Food protein-induced enterocolitis syndrome].
AB  - A little known pathology, increasingly diagnosed. Late vomiting after food intake
      predominate. An insidious chronic form, an explosive acute form. A clinical
      diagnosis of a typical story, reproducible. Milk and soy often involved,
      sometimes unusual foods.

PMID- 27712934
TI  - Effects of TiO2 nanoparticles and sunscreens on coastal marine microalgae:
      Ultraviolet radiation is key variable for toxicity assessment.
AB  - Given the large numbers of sunbathers on beaches, sunscreen compounds are being
      released into the coastal aquatic environment in significant amounts. Until now
      the effect of these potential pollutants on microbiota has been not well-known.
      Phytoplankton is a key component of the microbiota community. It forms the basis
      of the aquatic trophic networks, and any change in the natural population of
      phytoplankton can affect the structure of aquatic biota. This paper describes an
      experiment performed outdoors (in natural sunlight conditions including
      ultraviolet radiation (UVR) and with UVR blocked) on mixed microalgae populations
      (four species from different key marine taxonomic groups, Nannochloropsis
      gaditana, Chaetoceros gracilis, Pleurochrysis roscoffensis and Amphidinium
      carterae), for three days, exposed to a range of concentrations of three
      commercial sunscreens (with variable TiO2 concentrations: highest concentration
      for sunscreen C, followed by sunscreen A; and sunscreen B did not contain TiO2 in
      its composition). With regard to UVR effect, in the absence of sunscreens, the
      most sensitive species is the centric diatom, Chaetoceros gracilis, and the least
      is Nannochloropsis gaditana; this last species presented the same behavior in the
      absence of UVR and with high sunscreen concentrations. The toxicity gradient
      obtained for sunscreens and nanoparticles under UVR is: TiO2 NPs>Sunscreen
      C>Sunscreen A>Sunscreen B. The differential sensitivity of microalgae to
      sunscreens and TiO2 NPs can produce a change in the dynamics of phytoplankton
      populations and provoke undesirable ecological effects (such as giving
      dinoflagellates more prominence). The effects of UVR, commonly neglected in
      bioassays, could alter the results in important ways and should be considered
      when performing environmentally-relevant bioassays. The toxicity mediated by
      hydrogen peroxide production associated with the concentration of TiO2 NPs cannot
      be considered the only factor responsible for the toxicity: the organic compounds
      in the sunscreens must also be taken into account.

PMID- 27712935
TI  - Associations of night-time road traffic noise with carotid intima-media thickness
      and blood pressure: The Whitehall II and SABRE study cohorts.
AB  - BACKGROUND: Road traffic noise has been linked to increased risk of stroke, for
      which hypertension and carotid intima-media thickness (cIMT) are risk factors. A
      link between traffic noise and hypertension has been established, but there are
      few studies on blood pressure and no studies on cIMT. OBJECTIVES: To examine
      cross-sectional associations for long-term exposure to night-time noise with
      cIMT, systolic blood pressure (SBP), diastolic blood pressure (DBP) and
      hypertension. METHODS: The study population consisted of 2592 adults from the
      Whitehall II and SABRE cohort studies living within Greater London who had cIMT,
      SBP and DBP measured. Exposure to night-time road traffic noise (A-weighted dB,
      referred to as dBA) was estimated at each participant's residential postcode
      centroid. RESULTS: Mean night-time road noise levels were 52dBA (SD=4). In the
      pooled analysis adjusted for cohort, sex, age, ethnicity, marital status,
      smoking, area-level deprivation and NOx there was a 9.1MUm (95% CI: -7.1, 25.2)
      increase in cIMT in association with 10dBA increase in night-time noise. Analyses
      by noise categories of 55-60dBA (16.2MUm, 95% CI: -8.7, 41.2), and >60dBA
      (21.2MUm, 95% CI: -2.5, 44.9) vs. <55dBA were also positive but non-significant,
      expect among those not using antihypertensive medication and exposed to >60dBA
      vs. <55dBA (32.6MUm, 95% CI: 6.2, 59.0). Associations for SBP, DPB and
      hypertension were close to null. CONCLUSIONS: After adjustments, including for
      air pollution, the association between night-time road traffic noise and cIMT was
      only observed among non-medication users but associations with blood pressure and
      hypertension were largely null.

PMID- 27712936
TI  - GSK621 activates AMPK signaling to inhibit LPS-induced TNFalpha production.
AB  - LPS stimulation in macrophages/monocytes induces TNFalpha production. We here
      tested the potential effect of GSK621, a novel AMP-activated protein kinase
      (AMPK) activator, against the process. In RAW264.7 macrophages, murine bone
      marrow-derived macrophages (BMDMs), and chronic obstructive pulmonary disease
      (COPD) patients' monocytes, GSK621 significantly inhibited LPS-induced TNFalpha
      protein secretion and mRNA synthesis. Inhibition of AMPK, through AMPKalpha shRNA
      knockdown or dominant negative mutation (T172A), almost abolished GSK621's
      suppression on TNFalpha in RAW264.7 cells. Reversely, forced-expression of a
      constitutively-active AMPKalpha (T172D) mimicked GSK621 actions and reduced LPS
      induced TNFalpha production. Molecularly, GSK621 suppressed LPS-induced reactive
      oxygen species (ROS) production and nuclear factor kappa B (NFkappaB) activation.
      In vivo, GSK621 oral administration inhibited LPS-induced TNFalpha production and
      endotoxin shock in mice. In summary, GSK621 activates AMPK signaling to inhibit
      LPS-induced TNFalpha production in macrophages/monocytes.

PMID- 27712937
TI  - Will Medicare Readmission Penalties Motivate Hospitals to Reduce Arthroplasty
      Readmissions?
AB  - BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) recently imposed
      penalties against hospitals with above-average 30-day readmission rates following
      total joint arthroplasty (TJA). Hospitals must decide whether investments in
      readmission prevention are worthwhile. This study examines the financial
      incentives associated with unplanned readmissions before and after invocation of
      these penalties. METHODS: Financial data were reviewed for 2028 consecutive
      primary TJAs performed on Medicare beneficiaries over a 2-year period at an urban
      academic health system. Readmission penalties were estimated in accordance with
      CMS policies. RESULTS: Unplanned readmissions generated a $4416 median
      contribution margin. The initial hospitalizations (when the TJA was performed)
      were financially unfavorable for patients subsequently readmitted relative to
      those not readmitted due to increased costs of care (P = .002), but these costs
      were more than outweighed by the increased reimbursement earned during the
      readmission (P < .001), ultimately making readmitted patients financially
      preferable (P < .001). Going forward, penalties will be levied for risk-adjusted
      readmission rates above the national rate of 4.8%. For the institution under
      review, the penalty per readmission outweighs the financial gains earned through
      readmission by $12,184, resulting in a net loss from readmissions if the rate
      exceeds 6.5%. It will be financially optimal to maintain a readmission rate
      (after risk adjustment) equal to the national average but exceeding that rate
      will be $7768 more expensive per readmission than undershooting that target.
      CONCLUSION: If our results are generalizable, unplanned Medicare readmissions
      have traditionally been financially beneficial, but CMS penalties outweigh this
      benefit. Thus, penalties should incentivize institutions to maintain below
      average arthroplasty readmissions rates.

PMID- 27712938
TI  - Synthesis and anti-inflammatory activity of paeonol analogues in the murine model
      of complete Freund's adjuvant induced arthritis.
AB  - A new series of paeonol alkyl ether analogues were synthesized and confirmed with
      IR, 1H NMR, 13C NMR and HRMS spectra. They have shown anti-inflammatory
      activities by scavenging mediator of free radicals and inhibiting lipid mediator
      of inflammation on complete Freund's adjuvant (CFA) induced arthritis in mice.
      The in vitro and in vivo scavenging ability of free radicals was determined by
      using chemical analysis and commercial assay kits, respectively. The in vivo
      inhibiting lipid mediator of inflammation was examined by ELISA. Our results
      indicated that the substitution of the hydrogen in hydroxyl group at C2 position
      of paeonol 1 by short carbon chain, in the presence or absence of bromo atom at
      C5 position, decreased its scavenging ability on radicals (3a or 4a vs 1), while
      the long alkyl substitution (Cn>14) increased the activity. Compared with 3a or
      4a, scavenging abilities of 3a-h or 4a-h gradually increased following the length
      elongation of alkyl carbon chain. Compounds 3h and 4h showed great scavenging
      ability on OH, O2-, DPPH, ATBS+ and MDA, and good promotion on T-AOC and SOD. The
      results of the in vivo inhibiting lipid mediator of inflammation also
      demonstrated that 3h, 4h exhibited substantial inhibition on enzyme activity of
      COX-2, PGE2. Therefore, 3h and 4h have great potential to be the novel anti
      inflammatory drug candidates for the therapy of arthritis.

PMID- 27712939
TI  - Design, synthesis, and activity evaluation of selective inhibitors of anti
      apoptotic Bcl-2 proteins: The effects on the selectivity of the P1 pockets in the
      active sites.
AB  - The anti-apoptotic Bcl-2 proteins are attractive targets for anti-cancer drug
      development, and the discovery of their selective inhibitors has become a
      research focus. In this Letter, obvious differences in the P1 pocket of the
      active site between Bcl-2, Bcl-xL, and Mcl-1 proteins were proposed by the
      structural comparison of these proteins. As a result, the groups in their
      inhibitors binding to the P1 pockets may have significant effect on the
      selectivity for these proteins. Based on this hypothesis, five types of
      derivatives of the lead compound B-1 were designed, and several highly selective
      inhibitors of Bcl-xL (E-1) or Mcl-1 proteins (G) were found. The selective
      inhibitors of Mcl-1 protein found in this Letter provide new structural types for
      the development of novel antitumor agents.

PMID- 27712940
TI  - Host use and seasonality of Culex (Melanoconion) iolambdis (Diptera: Culicidae)
      from eastern Florida, USA.
AB  - Culex (Melanoconion) iolambdis (Dyar, 1918) is a mosquito (Diptera: Culicidae)
      species found throughout much of tropical America, including southern Florida.
      Relatively few reports are available regarding the ecology of Cx. iolambdis,
      despite its widespread distribution and putative involvement in transmission of
      Venezuelan equine encephalitis virus. To quantify habitat and host utilization,
      adults of Cx. iolambdis were sampled from resting shelters at a field site in
      Vero Beach, Florida, over a 12-month period. Culex iolambdis (1109 males, 3072
      females) constituted more than half (56.76%) of all mosquitoes sampled (24
      species) and was active year-round. Unfed females and gravid females of Cx.
      iolambdis were significantly more abundant in mangrove habitat, while males and
      blood-fed females were not. PCR-based bloodmeal analysis of 305 females revealed
      that Cx. iolambdis has very wide host breadth, feeding on birds (37.0% overall),
      reptiles (26.6%), amphibians (23.3%) and mammals (13.1%). Green heron (Butorides
      virescens), Southern leopard frog (Lithobates sphenocephala) and American
      alligator (Alligator mississippiensis) were the most commonly fed upon hosts.
      Bloodmeals from different host classes varied significantly with season,
      suggesting that Cx. iolambdis may play a role in the amplification and epidemic
      transmission of zoonotic arboviruses affecting human health.

PMID- 27712941
TI  - Effect of energy grass on methane production and heavy metal fractionation during
      anaerobic digestion of sewage sludge.
AB  - Anaerobic digestion (AD) is one of the most widely used processes to stabilize
      waste sewage sludge and produce biogas as renewable energy. The relatively low
      organic matter content and high heavy metal concentrations in sewage sludge have
      severely restricted the application and development of AD technology in China. In
      this study, the effect of energy grass (Pennisetum alopecuroides) addition on
      methane production and heavy metal fractionation during the AD of sewage sludge
      was evaluated. Methane production was enhanced by 11.2% by the addition of P.
      alopecuroides. The addition of P. alopecuroides significantly reduced the
      percentages of the water-soluble and exchangeable fractions of the target heavy
      metals in the sewage sludge after AD, and the dominant species were concentrated
      in Fe-Mn oxide-bound and organic- and sulfide-bound fractions of the digested
      sludge. The addition of P. alopecuroides at a dosage of 0.3kg significantly
      (P<0.05) decreased the mobility factors (MFs) of the target heavy metals after
      AD. In particular, the MFs of Cr and Ni were 61% and 32% lower, respectively,
      relative to the control. The increase in the added dose did not necessarily lead
      to further decreases in the MFs of the heavy metals. These results demonstrate
      that an appropriate addition of energy grass could enhance AD, decrease the
      mobility of heavy metals and promote heavy metal stabilization in sewage sludge
      during AD, which is beneficial for the subsequent land application of sewage
      sludge.

PMID- 27712942
TI  - Cost and efficiency of disaster waste disposal: A case study of the Great East
      Japan Earthquake.
AB  - This paper analyzes the cost and efficiency of waste disposal associated with the
      Great East Japan Earthquake. The following two analyses were performed: (1) a
      popular parametric approach, which is an ordinary least squares (OLS) method to
      estimate the factors that affect the disposal costs; (2) a non-parametric
      approach, which is a two-stage data envelopment analysis (DEA) to analyze the
      efficiency of each municipality and clarify the best performance of the disaster
      waste management. Our results indicate that a higher recycling rate of disaster
      waste and a larger amount of tsunami sediments decrease the average disposal
      costs. Our results also indicate that area-wide management increases the average
      cost. In addition, the efficiency scores were observed to vary widely by
      municipality, and more temporary incinerators and secondary waste stocks improve
      the efficiency scores. However, it is likely that the radioactive contamination
      from the Fukushima Daiichi nuclear power station influenced the results.

PMID- 27712943
TI  - Liberation of Printed Circuit Assembly (PCA) and dust generation in relation to
      mobile phone design in a size reduction process.
AB  - Complex electronic devices entering our recycling systems often generate losses
      in the whole treatment chain. For better liberation, crucial for the mechanical
      separation process, the devices are crushed which also generates dusts that are
      not recovered. This study investigated the relation between the liberation of
      Printed Circuit Assembly (PCA) and dust generation in the crushing process of two
      different types of mobile phone samples. The results revealed that the overall
      PCA grade in both samples was approximately 70% with around 3.4% dust generation.
      However, the liberation distribution of PCAs differed between mobile phones
      resulting in better distribution for sophisticated mobile phones due among other
      things to the initial size of the phones. Further, the dust fractions comprised
      both noble and valuable metals but also contaminants that need to be taken into
      account when further processing is planned. A higher gold concentrate was
      detected in dusts from regular phones since the protective plastic casing crushed
      more easily thus exposing the PCA surface for grinding.

PMID- 27712944
TI  - Degradation of organic pollutants by Ag, Cu and Sn doped waste non-metallic
      printed circuit boards.
AB  - The disposal and reuse of waste printed circuit boards have been the major global
      concerns. Printed circuit boards, a form of Electronic waste (hereafter e-waste),
      have been chemically processed, doped with Ag+, Cu2+ and Sn2+, and used as
      visible light photocatalysts against the degradation of methylene blue and methyl
      violet. The elemental analyses of pristine and metal doped printed circuit board
      were obtained using energy dispersive X-ray fluorescence (EDXRF) spectra and
      inductively coupled plasma optical emission spectroscopy (ICP-OES). The
      morphology of parent and doped printed circuit board was obtained from scanning
      electron microscopy (SEM) measurements. The photocatalytic activity of parent and
      metal doped samples was carried out for the decomposition of organic pollutants,
      methylene blue and methyl violet, under visible light irradiation. Metal doped
      waste printed circuit boards (WPCBs) have shown higher photocatalytic activity
      against the degradation of methyl violet and methylene blue under visible light
      irradiation. Scavenger experiments were performed to identify the reactive
      intermediates responsible for the degradation of methylene blue and methyl
      violet. The reactive species responsible for the degradation of MV and MB were
      found to be holes and hydroxyl radicals. A possible mechanism of degradation of
      methylene blue and methyl violet is given. The stability and reusability of the
      catalysts are also investigated.

PMID- 27712945
TI  - A holistic approach to the environmental evaluation of food waste prevention.
AB  - The environmental evaluation of food waste prevention is considered a challenging
      task due to the globalised nature of the food supply chain and the limitations of
      existing evaluation tools. The most significant of these is the rebound effect:
      the associated environmental burdens of substitutive consumption that arises as a
      result of economic savings made from food waste prevention. This study introduces
      a holistic approach to addressing these challenges, with a focus on greenhouse
      gas (GHG) emissions from household food waste in the UK. It uses a hybrid life
      cycle assessment model coupled with a highly detailed multi-regional
      environmentally extended input output analysis to capture environmental impacts
      across the global food supply chain. The study also takes into consideration the
      rebound effect, which was modelled using a linear specification of an almost
      ideal demand system. The study finds that food waste prevention could lead to
      substantial reductions in GHG emissions in the order of 706-896kg CO2-eq. per
      tonne of food waste, with most of these savings (78%) occurring as a result of
      avoided food production overseas. The rebound effect may however reduce such GHG
      savings by up to 60%. These findings provide a deeper insight into our
      understanding of the environmental impacts of food waste prevention: the study
      demonstrates the need to adopt a holistic approach when developing food waste
      prevention policies in order to mitigate the rebound effect and highlight the
      importance of increasing efficiency across the global food supply chain,
      particularly in developing countries.

PMID- 27712946
TI  - The Curious History of the Calorie in U.S. Policy:: A Tradition of Unfulfilled
      Promises.

PMID- 27712947
TI  - Supplemental Nutrition Assistance Program Reform:: Retail Requirements, Eligible
      Foods.

PMID- 27712948
TI  - Community Organizing for Healthier Communities: Environmental and Policy Outcomes
      of a National Initiative.
AB  - INTRODUCTION: Childhood obesity is disproportionately prevalent in communities of
      color, partially because of structural inequities in the social and built
      environment (e.g., poverty, food insecurity, pollution) that restrict healthy
      eating and active living. Community organizing is an underexamined, grassroots
      health promotion approach that empowers and mobilizes community residents to
      advocate for, and achieve, environmental and policy changes to rectify these
      structural inequities. This paper presents outcomes of the Robert Wood Johnson
      Foundation's Communities Creating Healthy Environments initiative: the first
      national program to apply community organizing to combat childhood obesity
      causing structural inequities in communities of color. METHODS: Twenty-one
      community-based organizations and tribal nations (grantees) conducted 3-year
      community organizing-based interventions primarily designed to increase
      children's healthy food and safe recreational access. Grantees' policy wins
      (environmental and policy changes resulting from grantee interventions) were
      measured from 2009 to 2014 using semi-structured interviews conducted quarterly
      and 6 months post-grant, and independently coded and reviewed in 2015 by
      researchers and expert community organizers. RESULTS: The 21 grantees achieved 72
      policy wins (mean=3.43, SD=1.78) across six domains: two directly addressed
      childhood obesity by enhancing children's healthy food (37.50%) and recreational
      access (33.33%), whereas four indirectly addressed obesity by promoting access to
      quality health care (8.33%); clean environments (9.73%); affordable housing
      (8.33%); and discrimination- and crime-free neighborhoods (2.78%). CONCLUSIONS:
      These findings provide compelling evidence that community organizing-based
      interventions designed and led by community stakeholders can achieve diverse
      environmental and policy solutions to the structural inequities that foment
      childhood obesity in communities of color.

PMID- 27712949
TI  - Assessing usability of the "Adherence Starts with Knowledge 20" (ASK-20)
      questionnaire for Japanese adults with bronchial asthma receiving inhaled
      corticosteroids long term.
AB  - BACKGROUND: Maintaining high treatment adherence levels is critical for effective
      management of chronic diseases. The Adherence Starts with Knowledge 20 (ASK-20)
      questionnaire is the only linguistically validated patient-reported treatment
      adherence tool available in Japan. We conducted additional analyses on ASK-20
      data from Japanese adults with asthma. METHODS: This was a prospective, non
      interventional, single-visit, multi-centre study in Japanese adults (n = 300)
      with asthma receiving long-term treatment with inhaled corticosteroids (ICS) or
      ICS/long-acting beta-agonists. We tested the reliability, validity and the
      relationship between different adherence conditions and ASK-20 score. At one
      centre, ICS adherence prescription rate was calculated retrospectively based on 2
      year percentage ICS adherence data contained within medical records. RESULTS: The
      ASK-20 had good internal consistency reliability (Cronbach's alpha = 0.76; n =
      290). Discriminant validity was demonstrated with significant correlations
      between the percentage ICS adherence rates and both the mean ASK-20 total score
      and mean total barrier count (TBC) (r = -0.51 and -0.58, p < 0.001; n = 111). The
      ASK-20 total score discriminated between subjects with good and poor adherence
      measured by patients' reported questionnaire and between those of high and low
      percentage ICS adherence rates. All other factors that possibly affect adherence
      were correlated with the mean ASK-20 total score and mean TBC in addition to the
      number of medicines taken every day. CONCLUSIONS: The Japanese ASK-20 is a
      reliable tool for assessing possible medication adherence barriers and adherence
      behaviour in Japanese adults with asthma. Furthermore, our results are comparable
      with those obtained using the ASK-20 in the United States.

PMID- 27712950
TI  - Health Disparities and the Microbiome.
AB  - An individual's microbiome is likely to be an important contributor to certain
      health disparity diseases and conditions. We present a framework to study the
      role of the microbiome and the multiple factors that are likely to influence
      differences in disease predisposition, onset, and progression at the individual
      and population level.

PMID- 27712951
TI  - Meningococcal Biofilm Formation: Let's Stick Together.
AB  - Extracellular DNA (eDNA) is an essential constituent of the extracellular matrix
      of biofilms of many microorganisms. In spite of many studies, it has long
      remained unclear how exactly eDNA exerts its role in biofilm formation. Here, we
      describe recent advances that have been made in understanding biofilm formation
      in the human pathogen Neisseria meningitidis. Several cell-surface-exposed
      proteins have been identified that bind DNA and other negatively charged
      polymers, such as heparin, by electrostatic interactions. By virtue of these
      proteins, eDNA can act as an adhesive that binds the bacteria together. We
      provide examples that indicate that the mechanism of binding eDNA via DNA/heparin
      binding proteins is a conserved feature in biofilms of many different
      microorganisms, including fungi.

PMID- 27712953
TI  - Shared decision making and the internist.
AB  - In this narrative review, we locate within the tradition of great diagnosticians
      in internal medicine, a fundamental development in patient-centered care: shared
      decision making (SDM). In this way, we present SDM as a core component of the
      clinical method, one in which diagnosis of the situation and of the actions that
      resolve it is essential toward the practice of evidence-based medicine.

PMID- 27712955
TI  - Neural stem cells from mouse strain Thy1 YFP-16 are a valuable tool to monitor
      and evaluate neuronal differentiation and morphology.
AB  - To analyse events following transplantation of stem cells in the brain robust
      tools for tracing stem cells are required. Here we took advantage of the mouse
      strain B6.Cg-Tg(Thy1-YFP)16Jrs/J (Thy1 YFP-16), where yellow fluorescent protein
      (YFP) is under control of the promoter of Thy1 gene. This allows visualising
      whole neurons, i.e. their cell body, axons and dendrites. In this work
      fluorescent cells were followed during embryonic development, in vitro
      differentiation, and after transplantation in the healthy and stroke-affected
      mouse brain. During embryonic development Thy1-YFP positive cells were first
      observed on E12.5 and subsequently located in the prosencephalon,
      rhombencephalon, spinal cord and peripheral nerves. Quantitative analysis by RT
      PCR and immunocytochemistry revealed that Thy1-YFP positive cells during embryo
      development and in vitro differentiation were expressing nestin and SOX2 then
      MAP2, beta3-tubulin and NeuN. Thy1-YFP positive cells isolated from E14.5
      represented 21.88+/-053% (SD) of the cultivated neurons and this remained
      constant along in vitro differentiation. On the other hand, proportion of Thy1
      YFP positive cells reached 50% of neurons in perinatal and one month old mouse
      brain. Neural stem cells isolated from Thy1 YFP-16 mouse strain transplanted near
      hippocampus of the healthy and stroke-affected brain were distinguishable by YFP
      fluorescence. They differentiated into mature neurons and were detectable even 14
      weeks after transplantation, the end point of our experiment. In conclusion, stem
      cells originating from Thy1 YFP-16 mice represent an outstanding tool to monitor
      neurogenesis enabling morphological analyses of new neurons and their
      projections, in particular after transplantation in the brain.

PMID- 27712952
TI  - Chlamydial Plasmid-Dependent Pathogenicity.
AB  - Most Chlamydia species carry a 7.5kb plasmid encoding eight open reading frames
      conventionally called plasmid glycoproteins 1-8 or pGP1-8. Although the plasmid
      is not critical for chlamydial growth in vitro, its role in chlamydial
      pathogenesis is clearly demonstrated in the genital tracts of mice infected with
      Chlamydia muridarum, a model for investigating the human pathogen Chlamydia
      trachomatis. Plasmid-free C. trachomatis is also attenuated in both the mouse
      genital tract and nonhuman primate ocular tissue. Deficiency in pGP3 alone, which
      is regulated by pGP4, largely reproduced the in vivo but not in vitro phenotypes
      of the plasmid-free organisms, suggesting that pGP3 is a key in vivo virulence
      factor. The positive and negative regulations of some chromosomal genes by pGP4
      and pGP5, respectively, may allow the plasmid to promote chlamydial adaptation to
      varied animal tissue environments. The focus of this review is to summarize the
      progress on the pathogenic functions of the plasmid-encoded open reading frames,
      which may motivate further investigation of the molecular mechanisms of
      chlamydial pathogenicity and development of medical utility of the chlamydial
      plasmid system.

PMID- 27712954
TI  - 2016 Canadian Cardiovascular Society Guidelines for the Management of
      Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult.
AB  - Since the publication of the 2012 guidelines new literature has emerged to inform
      decision-making. The 2016 guidelines primary panel selected a number of
      clinically relevant questions and has produced updated recommendations, on the
      basis of important new findings. In subjects with clinical atherosclerosis,
      abdominal aortic aneurysm, most subjects with diabetes or chronic kidney disease,
      and those with low-density lipoprotein cholesterol >= 5 mmol/L, statin therapy is
      recommended. For all others, there is an emphasis on risk assessment linked to
      lipid determination to optimize decision-making. We have recommended nonfasting
      lipid determination as a suitable alternative to fasting levels. Risk assessment
      and lipid determination should be considered in individuals older than 40 years
      of age or in those at increased risk regardless of age. Pharmacotherapy is
      generally not indicated for those at low Framingham Risk Score (FRS; <10%). A
      wider range of patients are now eligible for statin therapy in the FRS
      intermediate risk category (10%-19%) and in those with a high FRS (> 20%).
      Despite the controversy, we continue to advocate for low-density lipoprotein
      cholesterol targets for subjects who start therapy. Detailed recommendations are
      also presented for health behaviour modification that is indicated in all
      subjects. Finally, recommendation for the use of nonstatin medications is
      provided. Shared decision-making is vital because there are many areas in which
      clinical trials do not fully inform practice. The guidelines are meant to be a
      platform for meaningful conversation between patient and care provider so that
      individual decisions can be made for risk screening, assessment, and treatment.

PMID- 27712956
TI  - Alternative Splicing May Not Be the Key to Proteome Complexity.
AB  - Alternative splicing is commonly believed to be a major source of cellular
      protein diversity. However, although many thousands of alternatively spliced
      transcripts are routinely detected in RNA-seq studies, reliable large-scale mass
      spectrometry-based proteomics analyses identify only a small fraction of
      annotated alternative isoforms. The clearest finding from proteomics experiments
      is that most human genes have a single main protein isoform, while those
      alternative isoforms that are identified tend to be the most biologically
      plausible: those with the most cross-species conservation and those that do not
      compromise functional domains. Indeed, most alternative exons do not seem to be
      under selective pressure, suggesting that a large majority of predicted
      alternative transcripts may not even be translated into proteins.

PMID- 27712957
TI  - Increased risk for knee replacement surgery after arthroscopic surgery for
      degenerative meniscal tears: a multi-center longitudinal observational study
      using data from the osteoarthritis initiative.
AB  - OBJECTIVE: The primary objective was to assess whether patients with knee
      osteoarthritis and whom undergo arthroscopic meniscectomy have an increased risk
      for future knee replacement surgery. DESIGN: Data used were obtained from the
      Osteoarthritis Initiative (OAI) study. SETTING: Participants were enrolled, in
      four clinical centers, between February 2004 and May 2006 and were followed up on
      an annual basis up to and including 108-months from enrollment. PARTICIPANTS:
      4674 participants (58.4% female), aged 45-79, of all ethnic groups, who had, and
      those who were at high risk for developing, symptomatic knee osteoarthritis were
      included, of which 3337 (71.4%) were included in the final follow up visit. MAIN
      OUTCOME MEASURES: Hazard ratio of knee replacement surgery for participants who
      underwent arthroscopic meniscectomy during follow up compared to propensity score
      matched participants who did not undergo arthroscopic meniscectomy during follow
      up. RESULTS: 335 participants underwent arthroscopic meniscectomy during follow
      up, of which 63 (18.8%) underwent knee replacement surgery in the same knee. Of
      the 335 propensity score matched participants 38 (11.1%) underwent knee
      replacement surgery during follow up. Results from the Cox-proportional hazards
      model demonstrated that the hazard ratio of knee replacement surgery was 3.03
      (95% CI (1.67-5.26)) for participants who underwent arthroscopic meniscectomy
      relative to the propensity score matched participants who did not undergo
      arthroscopic meniscectomy. CONCLUSIONS: In patients with knee osteoarthritis
      arthroscopic knee surgery with meniscectomy is associated with a three fold
      increase in the risk for future knee replacement surgery.

PMID- 27712959
TI  - Mucoepidermoid carcinoma of the upper lip.

PMID- 27712960
TI  - Passive myofunctional therapy applied on children with obstructive sleep apnea: A
      6-month follow-up.
AB  - BACKGROUND/PURPOSE: Myofunctional therapy is one of the recommended treatments
      for obstructive sleep apnea, but the level of compliance has often been low in
      children. This study aims to investigate the therapeutic effect of passive
      myofunctional therapy using an oral appliance during sleep in children suffering
      from obstructive sleep apnea. METHODS: Twenty-nine children who suffered from
      obstructive sleep apnea were divided into two groups: premature children and full
      term children. All children wore an oral device to induce their tongue muscle
      activity during sleep for 6 months. Polysomnography during sleep was performed
      before and 1 week after the end of 6-month treatment. RESULTS: Both groups showed
      positive polysomnographic changes. Full-term children had a significant decrease
      in the apnea-hypopnea index, hypopnea index, and percentage of arousals.
      Prematurely born children had a significant decrease in the apnea-hypopnea index
      during rapid eye movement sleep and in the mean heart rate during sleep.
      CONCLUSION: Using a specialized oral device to perform myofunctional therapy
      during sleep may improve the breathing during sleep of children with obstructive
      sleep apnea.

PMID- 27712962
TI  - Risk factors for candidemia mortality in hospitalized children.
AB  - OBJECTIVE: To evaluate risk factors associated with death due to bloodstream
      infection caused by Candida spp. in pediatric patients and evaluate the
      resistance to the main anti-fungal used in clinical practice. METHODS: This is a
      cross-sectional, observational, analytical study with retrospective collection
      that included 65 hospitalized pediatric patients with bloodstream infection by
      Candida spp. A univariate analysis was performed to estimate the association
      between the characteristics of the candidemia patients and death. RESULTS: The
      incidence of candidemia was 0.23 cases per 1000patients/day, with a mortality
      rate of 32% (n=21). Clinical outcomes such as sepsis and septic shock (p=0.001),
      comorbidities such as acute renal insufficiency (p=0.01), and risks such as
      mechanical ventilation (p=0.02) and dialysis (p=0.03) are associated with
      increased mortality in pediatric patients. The resistance and dose-dependent
      susceptibility rates against fluconazole were 4.2% and 2.1%, respectively. No
      resistance to amphotericin B and echinocandin was identified. CONCLUSION: Data
      from this study suggest that sepsis and septic shock, acute renal insufficiency,
      and risks like mechanical ventilation and dialysis are associated with increased
      mortality in pediatric patients. The mortality among patients with candidemia is
      high, and there is no species difference in mortality rates. Regarding the
      resistance rates, it is important to emphasize the presence of low resistance in
      this series.

PMID- 27712961
TI  - Physical self-efficacy is associated to body mass index in schoolchildren.
AB  - OBJECTIVE: The present study aimed to investigate the relationship between
      physical self-efficacy and body mass index in a large sample of schoolchildren.
      METHODS: The Perceived Physical Ability Scale for Children was administered to
      1560 children (50.4% boys; 8-12 years) from three different countries. Weight and
      height were also recorded to obtain the body mass index. RESULTS: In agreement
      with the literature, the boys reported greater perceived physical self-efficacy
      than girls. Moreover, the number of boys who are obese is double that of girls,
      while the number of boys who are underweight is half that found in girls. In the
      linear regression model, the increase in body mass index was negatively related
      to the physical self-efficacy score, differently for boys and girls. Furthermore,
      age and nationality also were predictors of low physical self-efficacy only for
      girls. CONCLUSION: The results of this study reinforce the importance of
      psychological aspect of obesity, as the perceived physical self-efficacy and body
      mass index were negatively associated in a sample of schoolchildren for boys and
      girls.

PMID- 27712963
TI  - Effect of classic ketogenic diet treatment on lipoprotein subfractions in
      children and adolescents with refractory epilepsy.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of the classic
      ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein
      (HDL) subfractions in children and adolescents with refractory epilepsy. METHODS:
      This prospective study recruited children and adolescents of either sex, whose
      epilepsy was refractory to treatment with multiple drugs. To be included, the
      patient had to have an indication for treatment with the KD and be treated as an
      outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total
      cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL
      cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL,
      7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the
      Lipoprint system. RESULTS: The lipid profile components (TC, TG, LDL-C, HDL-C,
      apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent
      after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and
      apoB/apoA-I ratios, representing atherogenic particles, significantly increased.
      In contrast, qualitative lipoprotein characteristics progressively changed during
      the follow-up period. Small LDL subfractions increased, and this profile was
      related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became
      worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small
      HDL subfractions decreased only after 6 mo of the KD. CONCLUSIONS: KD treatment
      promotes negative changes in lipoprotein size and phenotype, contributing to
      atherogenic risk in these patients.

PMID- 27712958
TI  - Nutrients and the microenvironment to feed a T cell army.
AB  - T cells have dramatic functional and proliferative shifts in the course of
      maintaining immune protection from pathogens and cancer. To support these
      changes, T cells undergo metabolic reprogramming upon stimulation and again after
      antigen clearance. Depending on the extrinsic cell signals, T cells can
      differentiate into functionally distinct subsets that utilize and require diverse
      metabolic programs. Effector T cells (Teff) enhance glucose and glutamine uptake,
      whereas regulatory T cells (Treg) do not rely on significant rates of glycolysis.
      The dependence of these subsets on specific metabolic programs makes T cells
      reliant on these signaling pathways and nutrients. Metabolic pathways, such as
      those regulated by mTOR and Myc, augment T cell glycolysis and glutaminolysis
      programs to promote T cell activity. These pathways respond to signals and
      control metabolism through both transcriptional or post-transcriptional
      mechanisms. Epigenetic modifications also play an important role by stabilizing
      the transcription factors that define subset specific reprogramming. In addition,
      circadian rhythm cycling may also influence energy use, immune surveillance, and
      function of T cells. In this review, we focus on the metabolic and nutrient
      requirements of T cells, and how canonical pathways of growth and metabolism
      regulate nutrients that are essential for T cell function.

PMID- 27712964
TI  - Relationship between sodium and potassium intake and blood pressure in a sample
      of overweight adults.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between sodium
      and potassium intakes and blood pressure (BP) in a clinical sample. METHODS:
      Secondary analysis of baseline data from 328 participants (mean age: 43.6 +/- 8
      y, mean body mass index [BMI]: 32.4 +/- 4.2 kg/m2, mean systolic BP
      [SBP]/diastolic BP [DBP]: 124.9 +/- 14.5/73.3 +/- 9.9 mm Hg) of the 12-mo
      HealthTrack randomized controlled weight loss trial was conducted. Resting BP and
      24-h urine sodium and potassium were measured. Dietary intake was evaluated with
      4-d food records and self-reported diet histories. RESULTS: Urinary sodium was
      positively correlated (Spearman's rho) with SBP (r = 0.176; P = 0.001) and DBP (r
      = 0.150; P = 0.003). The ratio of sodium to potassium was positively correlated
      with SBP (r = 0.1; P = 0.035). Urinary sodium (F [4,323] = 20.381; P < 0.0005;
      adjusted R2 = 0.231) and sodium-to-potassium ratio (F[4,323] = 25.008; P <
      0.0005; adjusted R2 = 0.227) significantly predicted SBP after controlling for
      age, sex, BMI, and hypertension medication use. Dietary sodium and potassium
      significantly predicted urinary sodium (B = 0.33, t = 4.032, P < 0.01) and
      potassium (B = 0.67, t = 8.537, P < 0.01) excretion, respectively, after
      adjustment for energy and BMI. Median dietary sodium intake was 3197 mg/d and
      median dietary potassium intake was 2886 mg/d. Cereal-based products and dishes
      were the major contributors (22%) to total sodium intake. CONCLUSIONS: In the
      present study, a high dietary sodium intake and high sodium-to-potassium ratio
      predicted high SBP. This suggests a need to focus dietary advice on reduction of
      sources of sodium and increasing sources of potassium in weight loss
      interventions to improve BP control.

PMID- 27712965
TI  - Systemic inflammation, growth factors, and linear growth in the setting of
      infection and malnutrition.
AB  - OBJECTIVES: Deficits in weight gain and linear growth are seen frequently among
      children in areas where malnutrition and recurrent infections are common.
      Although both inflammation and malnutrition can result in growth hormone (GH)
      resistance, the interrelationships of infection, inflammation, and growth
      deficits in developing areas remain unclear. The aim of this study was to
      evaluate relationships between low levels of systemic inflammation, growth
      factors, and anthropometry in a case-control cohort of underweight and normal
      weight children in northern Brazil. METHODS: We evaluated data from 147 children
      ages 6 to 24 mo evaluated in the MAL-ED (Interactions of Malnutrition and Enteric
      Disease) case-control study following recruitment from a nutrition clinic for
      impoverished families in Fortaleza, Brazil. We used nonparametric tests and
      linear regression to evaluate relationships between current symptoms of
      infections (assessed by questionnaire), systemic inflammation (assessed by high
      sensitivity C-reactive protein [hsCRP]), the GH insulin-like growth factor-1 (IGF
      1) axis, and measures of anthropometry. All models were adjusted for age and sex.
      RESULTS: Children with recent symptoms of diarrhea, cough, and fever (compared
      with those without symptoms) had higher hsCRP levels; those with recent diarrhea
      and fever also had lower IGF-1 and higher GH levels. Stool myeloperoxidase was
      positively associated with serum hsCRP. hsCRP was in turn positively associated
      with GH and negatively associated with IGF-1 and IGF-binding protein-3 (IGFBP-3),
      suggesting a state of GH resistance. After adjustment for hsCRP, IGF-1 and IGFBP
      3 were positively and GH was negatively associated with Z scores for height and
      weight. CONCLUSIONS: Infection and inflammation were linked to evidence of GH
      resistance, whereas levels of GH, IGF-1, and IGFBP-3 were associated with growth
      indices independent of hsCRP. These data implicate complex interrelationships
      between infection, nutritional status, GH axis, and linear growth in children
      from a developing area.

PMID- 27712966
TI  - Impact of glucose tolerance status on the development of coronary artery disease
      among working-age men.
AB  - AIMS: To examine the impact of glucose tolerance status on the development of
      coronary artery disease (CAD) in working-age men in Japan. METHODS: This
      population-based retrospective cohort study included 111,621 men aged 31-60 years
      [63,558 with normal glucose tolerance (NGT); 37,126 with prediabetes; 10,937 with
      diabetes]. The Cox proportional-hazards regression model was used to identify
      variables related to the incidence of CAD. RESULTS: Multivariate analysis showed
      that, compared with NGT, diabetes increased the risk of CAD by 17.3 times (95%
      CI: 6.36-47.0) at ages 31-40 years, by 2.74 times (95% CI: 1.85-4.05) at ages 41
      50 years and by 2.47 times (95% CI: 1.69-3.59) at ages 51-60 years. The HRs for
      CAD in men with diabetes aged 31-40 equaled that of men with NGT aged 51-60 [18.2
      (7.15-46.4) and 19.4 (8.28-45.4), respectively]. CONCLUSION: The impact of
      diabetes on CAD was markedly greater in men aged 31-40 years compared with those
      aged 41-60 years.

PMID- 27712967
TI  - Pulmonic Regurgitation in the Adult Cardiac Surgery Patient.

PMID- 27712968
TI  - Surgical Versus Percutaneous Therapy of Carotid Artery Disease: An Evidence-Based
      Outcomes Analysis.

PMID- 27712969
TI  - Malpositioning of the Intra-atrial Baffle in a Case of Partial Anomalous
      Pulmonary Venous Connection-Role of Transesophageal Echocardiography in the
      Diagnosis and Management.

PMID- 27712970
TI  - Implementing a Statistical Model for Protamine Titration: Effects on Coagulation
      in Cardiac Surgical Patients.
AB  - OBJECTIVES: To implement a statistical model for protamine titration. DESIGN:
      Prospective randomized trial. SETTING: University hospital. PARTICIPANTS: Sixty
      (n = 30+30) patients scheduled for elective coronary artery bypass surgery were
      randomly assigned to 2 groups. INTERVENTIONS: Protamine dose calculated according
      to an algorithm established from a statistical model or to a fixed protamine
      heparin dose ratio (1:1). MEASUREMENTS AND MAIN RESULTS: Both groups demonstrated
      comparable patient demographics and intraoperative data. Coagulation effects were
      evaluated using rotational thromboelastometry. Using the statistical model
      reduced (p<0.01) the protamine dose from 426+/-43 mg to 251+/-66 mg, followed by
      significantly (p<0.01) shorter intrinsic clotting time (208+/-29 seconds versus
      244+/-52 seconds) and stronger clot firmness (p = 0.01), and effects on indices
      of extrinsic or fibrinogen coagulation pathways were insignificant. Test of
      residual heparin was negative in all patients after protamine administration,
      aligned with insignificant (p = 0.27) intergroup heparinase-verified clotting
      time differences. CONCLUSIONS: The statistical model for protamine titration is
      clinically feasible and protects the patient from exposure to excessive doses of
      protamine, with advantageous effects on coagulation as measured using rotational
      thromboelastometry. Significance regarding clinical outcome is yet to be defined.

PMID- 27712971
TI  - Corrigendum to ''Cell-free protein synthesis system from Escherichia coli cells
      cultured at decreased temperatures improves productivity by decreasing DNA
      template degradation'' [Anal. Biochem. 377 (2008) 156-161].

PMID- 27712972
TI  - Pyogenic liver abscess: current status and predictive factors for recurrence and
      mortality of first episodes.
AB  - BACKGROUND: In times of modern surgery, transplantation and percutaneous
      techniques, pyogenic liver abscess (PLA) has essentially become a problem of
      biliary or iatrogenic origin. In the current scenario, diagnostic approach,
      clinical behavior and therapeutic outcomes have not been profoundly studied. This
      study analyzes the clinical and microbiological features, diagnostic methods,
      therapeutic management and predictive factors for recurrence and mortality of
      first episodes of PLA. METHODS: A retrospective single-center study was conducted
      including 142 patients admitted to the Hospital Italiano de Buenos Aires, between
      2005 and 2015 with first episodes of PLA. RESULTS: Prevailing identifiable causes
      were biliary diseases (47.9%) followed by non-biliary percutaneous procedures
      (NBIPLA, 15.5%). Seventeen patients (12%) were liver recipients. Eleven patients
      (7.8%) died and 18 patients (13.7%) had recurrence in the first year of follow
      up. The isolation of multiresistant organisms (p = 0.041) and a history of
      cholangitis (p < 0.001) were independent risk factors for recurrence. Mortality
      was associated with serum bilirubin >5 mg/dL (p = 0.022) and bilateral
      involvement (p = 0.014) in the multivariate analysis. CONCLUSION: NBPLA and PLA
      after transplantation may be increasing among the population of PLA in referral
      centers. History of cholangitis is a strong predictor for recurrence. Mortality
      is associated to hiperbilirrubinemia and anatomical distribution of the lesions.

PMID- 27712974
TI  - Utility of cytopathological specimens and an automated image analysis for the
      evaluation of HER2 status and intratumor heterogeneity in breast carcinoma.
AB  - OBJECTIVES: Although updated HER2 testing guidelines have been improved by a
      collaboration between the American Society of Clinical Oncology (ASCO) and the
      College of American Pathologists (CAP) in 2013, HER2 evaluation is still
      problematic because of issues involving CEP17 polysomy, heterogeneity, and HER2
      score 2+ cases. The aim of this retrospective study was to evaluate the
      relationship between HER2 gene heterogeneity, or so called CEP17 polysomy, using
      breast carcinoma cells sampled by scraping and the IHC score graded by automated
      image analysis using whole slide image. MATERIAL AND METHODS: We randomly
      selected 23 breast carcinoma cases with a HER2 score 0, 24 cases with a HER2
      score 1+, 24 cases with HER2 score 2+, and 23 cases with HER2 score 3+ from the
      records of patients with breast cancer at Hiroshima University Hospital. We
      compared the results of fluorescent in situ hybridization (FISH) using formalin
      fixed, paraffin-embedded (FFPE) tissues and cytological samples and compared the
      HER2 score calculated using an automated image analysis using wholly scanned
      slide images and visual counting. RESULTS: We successfully performed the FISH
      assay in 78 of 94 cases (83%) using FFPE tissues and in all 94 (100%) cases using
      cytological samples. Frequency of both HER2 amplification and CEP17 polysomy was
      higher when cytological samples were used than when FFPE tissue was used.
      Frequency of HER2 heterogeneity using cytological samples was higher that than
      using FFPE tissue, except for the IHC score 3+ cases. CONCLUSIONS: When
      assessment of HER2 status based on FISH using FFPE tissue cannot be accomplished,
      FISH using cytological samples should be considered. When intensity of HER2 is
      heterogeneous in the tumor tissue, particularly in cases regarded as score 2+,
      they should be evaluated by automated image analysis using the whole slide image.

PMID- 27712973
TI  - Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive
      oxygen species (ROS) production in fungal cells.
AB  - BACKGROUND: Ebselen, an organoselenium compound and a clinically safe molecule
      has been reported to possess potent antifungal activity, but its antifungal
      mechanism of action and in vivo antifungal activity remain unclear. METHODS: The
      antifungal effect of ebselen was tested against Candida albicans, C. glabrata, C.
      tropicalis, C. parapsilosis, Cryptococcus neoformans, and C. gattii clinical
      isolates. Chemogenomic profiling and biochemical assays were employed to identify
      the antifungal target of ebselen. Ebselen's antifungal activity in vivo was
      investigated in a Caenorhabditis elegans animal model. RESULTS: Ebselen exhibits
      potent antifungal activity against both Candida spp. and Cryptococcus spp., at
      concentrations ranging from 0.5 to 2MUg/ml. Ebselen rapidly eradicates a high
      fungal inoculum within 2h of treatment. Investigation of the drug's antifungal
      mechanism of action indicates that ebselen depletes intracellular glutathione
      (GSH) levels, leading to increased production of reactive oxygen species (ROS),
      and thereby disturbs the redox homeostasis in fungal cells. Examination of
      ebselen's in vivo antifungal activity in two Caenorhabditis elegans models of
      infection demonstrate that ebselen is superior to conventional antifungal drugs
      (fluconazole, flucytosine and amphotericin) in reducing Candida and Cryptococcus
      fungal load. CONCLUSION: Ebselen possesses potent antifungal activity against
      clinically relevant isolates of both Candida and Cryptococcus by regulating GSH
      and ROS production. The potent in vivo antifungal activity of ebselen supports
      further investigation for repurposing it for use as an antifungal agent. GENERAL
      SIGNIFICANCE: The present study shows that ebselen targets glutathione and also
      support that glutathione as a potential target for antifungal drug development.

PMID- 27712975
TI  - Decreased PLK1 expression denotes therapy resistance and unfavourable disease
      free survival in rectal cancer patients receiving neoadjuvant chemoradiotherapy.
AB  - AIM: Polo-like kinase 1 (Plk1) plays a key role in mitotic cell division and DNA
      damage repair. It has been observed that either up-regulated or down-regulated
      Plk1 could induce mitotic defects that results in aneuploidy and tumorigenesis,
      probably depending on the context. Few previous reports have associated Plk1
      expression with prognosis and response to radiotherapy in rectal carcinomas. The
      aim of this study is to investigate the prognostic impact of Plk1 expression and
      its role in predicting response to neoadjuvant cheomoradiotherapy in rectal
      cancer. METHODS AND RESULTS: Immunohistochemical analysis of Plk1 expression was
      performed in the pre-treatment tumour specimens from 75 rectal cancer patients.
      We analysed the assocation between Plk1 expression and clinicopathological
      parameters, pathologic response and outcome. Opposed to previous reports on this
      issue, low expression of Plk1 was significantly associated with a high grade of
      differentiation (P=0.0007) and higher rate of distant metastasis (P=0.014). More
      importantly, decreased levels of Plk1 were associated with absence of response
      after neoadjuvant therapy (P=0.049). Moreover, low Plk1 expression emerged as an
      unfavourable prognostic factor for disease-free survival in the non-responder
      group of patients (P=0.037). CONCLUSIONS: Decreased Plk1 expression was
      associated with poor pathologic response and worse disease-free survival in
      rectal cancer patients receiving neoadjuvant chemoradiotherapy, suggesting Plk1
      as a clinically relevant marker to predict chemoradiotherapy response and
      outcome.

PMID- 27712976
TI  - A rare, low-grade appendiceal mucinous neoplasm (Pseudomyxoma peritonei) with
      ossification: A case report with morphoproteomic analysis of bone formation.
AB  - Heterotopic ossification occurring to low-grade appendiceal mucinous neoplasm
      (LAMN) (pseudomyxoma peritonei) is extremely rare. The pathogenetic mechanism of
      the tumor-related heterotopic bone formation remains as yet unconfirmed. Here, we
      describe a rare case of LAMN with ossification in a 72-year-old woman, and
      concentrate on the etiology of heterotopic ossification by the
      immunohistochemical evaluation of the novel markers such as BMP9, osteocalcin,
      and osteopontin. BMP9 is one of the most effective osteogenetic proteins.
      However, no researches associated with BMP9 in the heterotopic ossification
      occurring to LAMN have been performed. Consequently, we suggest the trustworthy
      hypothesis of tumor-associated heterotopic bone formation through this case. When
      osteoblastic markers such as BMP9, osteocalcin, and osteopontin are overexpressed
      in tumor cells, osteoblast-like transformation of such tumor cells occurs. In
      turn, these tumor cells increase secretion of interactive osteogenetic factors,
      such as BMP9, osteocalcin, and osteopontin, thus contributing to heterotopic bone
      formation through a microenvironmental change to mesenchymal stromal cells
      (osteoblastic differentiation). This phenomenon is considered a type of EMT.
      Patients should be followed closely because EMT-like transformed tumors have
      shown a tendency toward local recurrence. Our findings provide insight into the
      pathogenetic etiology of the heterotopic ossification in LAMN (pseudomyxoma
      peritonei).

PMID- 27712977
TI  - Breast cancer in young women of Chinese Han population: A retrospective study of
      patients under 25 years.
AB  - BACKGROUND: Breast cancer has aggressive clinical and pathological features in
      younger women and is characterized by poorer prognosis than in older women.
      However, data on women <25 years are limited. OBJECTIVE: The aim of the present
      study was to evaluate the different pathological characteristics and prognostic
      factors in Chinese women with breast cancer <25 years at the time of diagnosis.
      METHODS: This retrospective study included 94 patients (aged <25) of Chinese Han
      population with operable breast cancer at the National Cancer Center/Cancer
      Hospital, Chinese Academy of Medical Sciences between January 1, 2000 and
      September 30, 2015. Univariate and multivariate Cox regression analysis were
      performed. The median follow-up duration was 64 months (range, 11-200 months).
      RESULTS: The HER2-positive and triple-negative groups had a higher T (P=0.002)
      and N stage than the luminal A group (P=0.014). The 5-year overall survival (OS)
      was 90.4%, and the disease-free survival (DFS) was 74.5%. The 5-year DFS varied
      among the four groups were 94.1 vs. 76.9 vs. 45.5 vs. 66.7%, respectively;
      P=0.009. Multivariate analysis showed that only estrogen receptor (ER) status was
      a significant predictor of OS and DFS [Hazard ratio (HR)=5.3, 95% confidence
      interval (CI)=1.11-25.27, P=0.036; HR=2.712, 95%CI=1.27-5.80, P=0.01).
      CONCLUSION: HER2-positive and triple-negative breast cancer are more likely to
      have poor prognosis in patients<25years. Hence, ER status may be identified as an
      independent prognostic factor for predicting young women with breast cancer.

PMID- 27712978
TI  - MMP-14 promotes VSMC migration via up-regulating CD44 expression in cardiac
      allograft vasculopathy.
AB  - Cardiac allograft vasculopathy (CAV) was the leading cause of late death in heart
      transplantation recipients. Matrix metalloproteinase-14 (MMP-14), as a member of
      the MMPs family, has been reported to play a vital role in coronary vascular
      lesions of allotransplanted hearts. However, concrete mechanism is still unclear.
      Herein, we showed that the expression of MMP-14 was different between isografts
      and allografts. Interestingly, we found MMP-14 could interact with CD44 in
      allografts. Cluster of differentiation 44 (CD44), as a cell adhesion receptor and
      is involved in cell migration, caused our interest in MMP-14/CD44 complex in
      allografts. Then we analyzed the effect of MMP-14/CD44 complex on pro-MMP-9
      activation and vascular smooth muscle cell (VSMC) migration in rat VSMC TNF-alpha
      treated model. Then, we further found intervention of MMP-14/CD44 complex could
      inhibit VSMC migration. Our results elucidate the molecular mechanism of VSMC
      migration after cardiac transplantation and provide theoretical basis for seeking
      new specific drug targets for CAV prevention and treatment.

PMID- 27712979
TI  - Novel polyacrylate-based cationic nanoparticles for survivin siRNA delivery
      combined with mitoxantrone for treatment of breast cancer.
AB  - As a gene delivery method in breast cancer therapy, knocking down the undesired
      genes in the cancerous cells would be promising. Inhibitors of Apoptosis Protein
      (IAP) family genes are some of the genes whose responsibility is inhibition of
      apoptosis in cells. Silencing these genes seems to be helpful directing the tumor
      cells to death. siRNA sequence designed against survivin anti-apoptotic gene can
      play this role if carried to the cytoplasm. Here we prepared a positive charged
      biocompatible nano-sized particle made up of a Fe3O4 core covered respectively by
      polyacrylate (PA) and polyethyleneimine (PEI) layer, which could successfully
      deliver the siRNA into the MCF-7 cells. The particle structure was checked and
      having less than 50 nm diameter in size, positive charge and, safety towards MCF
      7 cells besides being able to form nanoplexes with the siRNA strand helps it
      entering into the biologic assays part. The siRNA delivery evaluated via
      flowcytometry. Apoptosis induction was determined by DAPI staining. The
      efficiency of survivin gene knockdown was evaluated in mRNA and protein levels
      using Real time PCR and western blotting methods. Overall, the Fe3O4-PA-PEI
      nanoparticles can deliver siRNA effectively into the cytoplasm of the MCF-7
      breast cancer cells and induce apoptosis.

PMID- 27712980
TI  - Resampling: An improvement of importance sampling in varying population size
      models.
AB  - Sequential importance sampling algorithms have been defined to estimate
      likelihoods in models of ancestral population processes. However, these
      algorithms are based on features of the models with constant population size, and
      become inefficient when the population size varies in time, making likelihood
      based inferences difficult in many demographic situations. In this work, we
      modify a previous sequential importance sampling algorithm to improve the
      efficiency of the likelihood estimation. Our procedure is still based on features
      of the model with constant size, but uses a resampling technique with a new
      resampling probability distribution depending on the pairwise composite
      likelihood. We tested our algorithm, called sequential importance sampling with
      resampling (SISR) on simulated data sets under different demographic cases. In
      most cases, we divided the computational cost by two for the same accuracy of
      inference, in some cases even by one hundred. This study provides the first
      assessment of the impact of such resampling techniques on parameter inference
      using sequential importance sampling, and extends the range of situations where
      likelihood inferences can be easily performed.

PMID- 27712982
TI  - Colonic Hemosuccus Pancreaticus.

PMID- 27712981
TI  - Weight Loss Decreases Magnetic Resonance Elastography Estimated Liver Stiffness
      in Nonalcoholic Fatty Liver Disease.

PMID- 27712983
TI  - Acculturation and Nonalcoholic Fatty Liver Disease Risk Among Hispanics of
      Mexican Origin: Findings From the National Health and Nutrition Examination
      Survey.

PMID- 27712984
TI  - Recent Discoveries in the Genetics of Familial Colorectal Cancer and Polyposis.
AB  - The development of genome-wide massively parallel sequencing, ie, whole-genome
      and whole-exome sequencing, and copy number approaches has raised high
      expectations for the identification of novel hereditary colorectal cancer genes.
      Although relatively successful for genes causing adenomatous polyposis syndromes,
      both autosomal dominant and recessive, the identification of genes associated
      with hereditary non-polyposis colorectal cancer has proven extremely challenging,
      mainly because of the absence of major high-penetrance genes and the difficulty
      in demonstrating the functional impact of the identified variants and their
      causal association with tumor development. Indeed, most, if not all, novel
      candidate non-polyposis colorectal cancer genes identified so far lack
      corroborative data in independent studies. Here we review the novel hereditary
      colorectal cancer genes and syndromes identified and the candidate genes proposed
      in recent years as well as discuss the challenges we face.

PMID- 27712985
TI  - [Quality of professional life and musculoskeletal disorders in nurses].
AB  - OBJECTIVE: To characterize the conditions of quality of working life, the
      presence of muscle- skeletal disorders and the association between these
      variables in nursing staff of a public hospital in Zacatecas, Mexico. METHOD: A
      cross-sectional study with descriptive-correlational scope was designed. A
      stratified random sampling per shift was used in 107 cases. The Questionnaire
      Professional Quality of Life (CVP-35) was applied as well as the Nordic
      Questionnaire Standardized for musculoskeletal pain and work-related risk factors
      questionnaire. RESULTS: The quality of working life gained an average of 55.62
      (SD=13.57), the intrinsic motivation was the best rated component with (M=75.06,
      SD=18.44), contrary to managerial support that got the lowest scores with
      (M=43.74, SD=21.71). The presence of risk factors in the development work of
      musculoskeletal problems obtained a mean of 50.10 (SD=26.69). The main
      musculoskeletal disorders occurred in the neck region, lumbar spine and knees
      with 42.1% for each one. The quality of working life decreased in the presence of
      muscle-skeletal problems in the lumbar region with (-0.188, p<=.050), dorsal (
      0.206, p<=.050), neck (-0.175, p<=.050) and knees (-0.220, p<=.010). CONCLUSIONS:
      It is necessary to improve the working conditions of nurses to reduce the
      presence of musculoskeletal problems and improve their quality of working life.

PMID- 27712986
TI  - Increased Bone Mineral Density in Cervical or Thoracic Diffuse Idiopathic
      Skeletal Hyperostosis (DISH): A Case-Control Study.
AB  - We aim to compare the bone mineral density (BMD) in a group of patients with
      cervical or thoracic diffuse idiopathic skeletal hyperostosis (DISH) with that in
      a matched control group. We also investigated the prevalence of osteoporosis in
      the two groups and determined the correlation between BMD and the extent of
      spinal DISH. From 1999 to July 2015, 65 patients with DISH underwent dual-energy
      X-ray absorptiometry at our institute. The control group was matched with regard
      to age, sex, and body mass index to the patient group on a 1:1 basis. BMD was
      measured at the lumbar spine (L1-L4), femur neck, and femur total areas using
      dual-energy X-ray absorptiometry. The BMDs of the DISH and control groups were
      significantly different at the lumbar spine (L1-L4) and the femur neck (p =
      0.005, 0.001). The rates of patients with osteopenia and osteoporosis were lower
      in the DISH than in the control group for the lumbar spine (L1-L4) (p = 0.05). A
      positive correlation was observed between the lumbar spine (L1-L4) BMD and the
      number of spine levels affected by DISH (p = 0.04). The BMDs of the lumbar spine
      and femur neck were found to be higher in the DISH group than in a matched
      control group, when patients with lumbar DISH involvement were excluded. The
      rates of osteopenia and osteoporosis tended to be lower in the DISH group than in
      the control group. Lumbar spine BMD is significantly correlated with the number
      of spine levels affected by DISH.

PMID- 27712987
TI  - Impact of physical activity of individuals and creatine kinase on 99th
      percentiles of troponin I assays.
AB  - Determination of cardiac troponin I (cTnI) is one central means for diagnosis of
      myocardial infarction. Assay performance of three troponin I assays was compared
      previously in a large reference population detecting sex-differences in the 99th
      percentile only for the Dimension Vista cTnI assay. The present study examined
      the underlying effects. Values for cTnI were reused. Creatine kinase (CK)
      activity was determined in 2358 samples from blood donors. Information on
      physical activity was evaluated from health questionnaires. Using quantile
      regression data were analysed to investigate the impact of sex, physical
      activity, and CK on the 99th percentile of the cTnI assay. We report significant
      sex-differences for the 99th percentile of cTnI. Physical activity was
      significantly associated with cTnI values. Strong association of CK activity with
      cTnI values was detected only in men. Adjustment for CK in quantile regression
      abolished sex-differences in the 99th percentile. Two other contemporary
      sensitive cTnI assays were not relevantly affected by physical activity or CK.
      Sex-differences in the 99th percentile for the Dimension Vista cTnI assay arise
      from a positive association between cTnI and physical activity and were abrogated
      when data were adjusted for CK activity. These findings should be taken into
      account when using this assay.

PMID- 27712988
TI  - Estimated glomerular filtration rate calculated using different creatinine and
      cystatin based formulas in prediction of trough plasma Dabigtran concentration.
AB  - BACKGROUND: In this paper we evaluated the relationship between trough DAB
      concentration with eGFR calculated using CRE and CYS based formulas. MATERIALS
      AND METHODS: We considered 100 patients. eGFR was calculated using CKD-EPIcreat,
      CG, MDRD, CKD-EPIcys and CKD-EPIcombined equations. DAB dosage was selected on
      the basis of CKD-EPIcreat and relationship between trough DAB concentration and
      eGFRs was evaluated. RESULTS: Trough DAB concentration roughly correlates with
      eGFR calculated using various formulas. CKD-EPIcreat eGFR was higher than CKD
      EPIcys. In patients receiving a DAB dosage considered adequate using CKD-EPIcreat
      eGFR but considered excessive using CKD-EPIcys, we observed higher DAB trough
      concentration and an increased prevalence of subjects with drug concentration
      >200ng/mL. CONCLUSION: These results suggest that eGFR alone was unable to fully
      explain trough DAB plasma concentration. Therefore a drug's prescription schedule
      based on eGFR only should be inadequate. We observed a better correlation between
      trough DAB concentration and CKD-EPIcys rather than CKD-EPIcreat eGFR. Thus, in
      patients chronically treated with DAB for thromboprophylaxis in nonvalvular
      atrial fibrillation evaluation of eGFR using a cystatin base formula should be
      considered.

PMID- 27712989
TI  - Nuclear spin-lattice relaxation in nitroxide spin-label EPR.
AB  - Nuclear relaxation is a sensitive monitor of rotational dynamics in spin-label
      EPR. It also contributes competing saturation transfer pathways in T1-exchange
      spectroscopy, and the determination of paramagnetic relaxation enhancement in
      site-directed spin labelling. A survey shows that the definition of nitrogen
      nuclear relaxation rate Wn commonly used in the CW-EPR literature for 14N
      nitroxyl spin labels is inconsistent with that currently adopted in time-resolved
      EPR measurements of saturation recovery. Redefinition of the normalised 14N spin
      lattice relaxation rate, b=Wn/(2We), preserves the expressions used for CW-EPR,
      whilst rendering them consistent with expressions for saturation recovery rates
      in pulsed EPR. Furthermore, values routinely quoted for nuclear relaxation times
      that are deduced from EPR spectral diffusion rates in 14N-nitroxyl spin labels do
      not accord with conventional analysis of spin-lattice relaxation in this three
      level system. Expressions for CW-saturation EPR with the revised definitions are
      summarised. Data on nitrogen nuclear spin-lattice relaxation times are compiled
      according to the three-level scheme for 14N-relaxation: T1n=1/Wn. Results are
      compared and contrasted with those for the two-level 15N-nitroxide system.

PMID- 27712990
TI  - Influence of concurrency, partner choice, and viral suppression on racial
      disparity in the prevalence of HIV infected women.
AB  - In 1992, Watts and May introduced a simple dynamical systems model of the spread
      of HIV based on disease transmission per partnership including the length of
      partnership duration. This model allowed for the treatment of concurrent
      partnerships, although it was hampered by the assumption of an important latent
      phase which generated a non-autonomous system. Subsequent models including
      concurrency have been based on networks, Monte Carlo, and stochastic simulations
      which lose a qualitative understanding of the effects of concurrency. We present
      a new autonomous deterministic model of the effect of concurrent sexual
      partnerships that allows for an analytical study of disease transmission. We
      incorporate the effect of concurrency through the newly derived force of
      infection term in a mathematical model of the transmission of HIV through sexual
      contact in a population stratified by sexual behavior and race/ethnicity. The
      model also includes variations in population mixing (partner choice) and non
      uniform Highly Active Anti-Retroviral Treatment (HAART) leading to viral
      suppression. We use this mathematical model to understand the non-uniform spread
      of HIV in women who were infected through heterosexual contact. In addition, an
      analytical study shows the importance of continued condom use in virally
      suppressed MSM. Numerical simulations of the reproduction number as a function of
      concurrency, viral suppression level, and mixing show a reservoir of disease
      present in both heterosexual and MSM populations. Statistical analysis of
      parameter values show that viral suppression level, mixing and progression to
      AIDS without viral suppression have a strong correlation (either positive or
      negative) with the number of HIV positive women. Concurrency and assortative
      mixing are shown to be essential to reproduce infection levels in women, as
      reported by 2010 data from the Center for Disease Control (CDC).

PMID- 27712991
TI  - Sensitivity and elasticity analysis of a Lur'e system used to model a population
      subject to density-dependent reproduction.
AB  - Sensitivity and elasticity analyzes have become central to the analysis of models
      in population biology and ecology. While much work has been done applying
      sensitivity and elasticity analysis to study density-independent (linear) matrix
      and integral projection models, little work has been done to study the
      sensitivity and elasticity of density-dependent models, especially integral
      projection models. In this paper we derive sensitivity and elasticity formulas
      for the equilibrium population n* of a structured population modeled by a Lur'e
      system, which consists of a linear system plus a nonlinearity modeling density
      dependent fecundity. Sensitivity and elasticity formulas are easy to interpret
      ecologically, and we apply these formulas to published models for Chinook Salmon
      and Platte thistle (Cirsium canescens). In the C. canescens example we show that
      models with identical equilibrium populations can have sensitivities that are an
      order-of-magnitude apart, depending on the functional form for the nonlinearity.

PMID- 27712992
TI  - Smartphone-based sensing system using ZnO and graphene modified electrodes for
      VOCs detection.
AB  - Volatile organic compounds (VOCs) detection is in high demand for clinic
      treatment, environment monitoring, and food quality control. Especially, VOCs
      from human exhaled breath can serve as significant biomarkers of some diseases,
      such as lung cancer and diabetes. In this study, a smartphone-based sensing
      system was developed for real-time VOCs monitoring using alternative current (AC)
      impedance measurement. The interdigital electrodes modified with zinc oxide
      (ZnO), graphene, and nitrocellulose were used as sensors to produce impedance
      responses to VOCs. The responses could be detected by a hand-held device, sent
      out to a smartphone by Bluetooth, and reported with concentration on an android
      program of the smartphone. The smartphone-based system was demonstrated to detect
      acetone at concentrations as low as 1.56ppm, while AC impedance spectroscopy was
      used to distinguish acetone from other VOCs. Finally, measurements of the
      exhalations from human being were carried out to obtain the concentration of
      acetone in exhaled breath before and after exercise. The results proved that the
      smartphone-based system could be applied on the detection of VOCs in real
      settings for healthcare diagnosis. Thus, the smartphone-based system for VOCs
      detection provided a convenient, portable and efficient approach to monitor VOCs
      in exhaled breath and possibly allowed for early diagnosis of some diseases.

PMID- 27712993
TI  - Response to the commentary on mechanical properties of cortical bone and their
      relationships with age, gender, composition and microindentation properties in
      the elderly.

PMID- 27712994
TI  - Identification of high-affinity anti-CD16A allotype-independent human antibody
      domains.
AB  - CD16A (FcgammaRIIIA) is an activating receptor mostly expressed on natural killer
      (NK) cells and monocytes/macrophages. It can mediate antibody-dependent cell
      mediated cytotoxicity (ADCC) through low-affinity interaction with human
      immunoglobulin G (IgG) Fc. It can also mediate cell lysis if NK cells are guided
      by bispecific killer cells engagers (BiKEs). BiKEs showed some success in
      clinical trials of cancer and are promising candidate therapeutics. However,
      currently reported BiKEs are based on antibody fragments (scFvs) of relatively
      large size. The CD16A-specific antibodies are also typically from animal origin.
      Decreasing the BiKE size could result in enhanced penetration into solid tumor
      and normal tissues, and using fully human antibodies could decrease the
      likelihood of immunogenicity. Here we report the identification and
      characterization of two antibody domains, D6 and E11, isolated from a very large
      human VH antibody domain library displayed on phage. D6 and E11 bound CD16A with
      EC50 of 4nM and 8nM, respectively, but not other Fc gamma receptors (FcgammaRs)
      such as CD64 (FcgammaRI), CD32 (FcgammaRII) and CD16B (FcgammaRIIIB). They bound
      to both CD16A allotypes (158F,V) with equal affinity and competed with each other
      as well as with human IgG1 and the mouse anti-CD16A antibody 3G8. These and other
      results were used to build a molecular docking model predicting that D6 and E11
      may bind to the CD16A membrane proximal D2 domain by interacting with its BC, C'E
      and EF loops. Importantly, cross-linked (bivalent) D6 and E11 induced secretion
      of IL-2 after binding to CD16A-expressing Jurkat T cells. The small size of these
      antibody domains combined with their high-affinity, specific, allotype
      independent, activating interactions with CD16A could allow generation of novel
      highly effective BiKEs and other candidate protein therapeutics.

PMID- 27712996
TI  - Traumatic open globe injury in young pediatric patients: characterization of a
      novel prognostic score.

PMID- 27712997
TI  - Revisiting secondary capsulotomy for posterior capsule management in pediatric
      cataract surgery.
AB  - PURPOSE: To evaluate the development and treatment of visual axis opacification
      following pediatric cataract extraction with intraocular lens placement (IOL)
      without primary posterior capsulotomy and anterior vitrectomy (PPC+AV). METHODS:
      The medical records of children who underwent cataract extraction and IOL at an
      academic medical center were reviewed retrospectively for development of
      posterior capsular opacification (PCO) to identify risk factors for development
      of treatment-requiring posterior capsular opacification. RESULTS: A total of 63
      eyes of 47 children 7 months to 16 years of age were included. The rate of PCO
      formation following cataract extraction without PPC+AV was 90%. Of those, 96%
      required a secondary capsular procedure to clear the visual axis; 55% had a clear
      visual axis after 1 procedure, almost exclusively with a YAG capsulotomy, and
      3.5% did not require any secondary capsular procedure. Younger age was the only
      statistically significant characteristic associated with both PCO formation and
      need for more than one secondary capsular procedure. Children <3 years of age had
      an average of 2.1 capsular procedures. CONCLUSIONS: Cataract extraction and IOL
      without PPC+AV leads to an expected high rate of PCO formation, which can be
      effectively managed with a secondary capsular procedure in all age groups.
      Leaving the posterior capsule intact at primary surgery is an option to discuss
      with parents to avoid a more complicated primary surgery.

PMID- 27712995
TI  - Combination strategy of PARP inhibitor with antioxidant prevent bioenergetic
      deficits and inflammatory changes in CCI-induced neuropathy.
AB  - Neuropathic pain, a debilitating pain condition and the underlying pathogenic
      mechanisms are complex and interwoven amongst each other and still there is scant
      information available regarding therapies which promise to treat the condition.
      Evidence indicate that oxidative/nitrosative stress induced poly (ADP-ribose)
      polymerase (PARP) overactivation initiate neuroinflammation and bioenergetic
      crisis culminating into neurodegenerative changes following nerve injury. Hence,
      we investigated the therapeutic effect of combining an antioxidant, quercetin and
      a PARP inhibitor, 4-amino 1, 8-naphthalimide (4-ANI) on the hallmark deficits
      induced by chronic constriction injury (CCI) of sciatic nerve in rats. Quercetin
      (25 mg/kg, p.o.) and 4-ANI (3 mg/kg, p.o.) were administered either alone or in
      combination for 14 days to examine sciatic functional index, allodynia and
      hyperalgesia using walking track analysis, Von Frey, acetone spray and hot plate
      tests respectively. Malondialdehyde, nitrite and glutathione levels were
      estimated to detect oxidative/nitrosative stress; mitochondrial membrane
      potential and cytochrome c oxidase activity to assess mitochondrial function; NAD
      & ATP levels to examine the bioenergetic status and levels of inflammatory
      markers were evaluated in ipsilateral sciatic nerve. Quercetin and 4-ANI alone
      improved the pain behaviour and biochemical alterations but the combination
      therapy demonstrated an appreciable reversal of CCI-induced changes.
      Nitrotyrosine and Poly ADP-Ribose (PAR) immunopositivity was decreased and
      nuclear factor erythroid 2-related factor (Nrf-2) levels were increased
      significantly in micro-sections of the sciatic nerve and dorsal root ganglion
      (DRG) of treatment group. These results suggest that simultaneous inhibition of
      oxidative stress-PARP activation cascade may potentially be useful strategies for
      management of trauma induced neuropathic pain.

PMID- 27712999
TI  - Evaluation of the cytotoxic, apoptosis inducing activity and molecular docking of
      spiroquinazolinone benzamide derivatives in MCF-7 breast cancer cells.
AB  - Previous studies have suggested that quinazolinone derivatives are potent
      apoptosis-inducing agents in various cancer cell lines. In the present study, we
      have investigated cytotoxic, apoptosis induction, and molecular docking
      activities of the spiroquinazolinone benzamide derivatives family on MCF-7 human
      breast cancer cells. The MTT cytotoxicity assays and docking studies showed that
      4t-CHQB was the most active compound among the prepared spiroquinazolinone
      benzamide compounds with IC50 of 50 +/- 1.2 MUM and was selected for further
      assessments. Apoptosis, as the mechanism of cell death, was assessed
      morphologically by acridine orange/ethidium bromide (AO/EtBr) double staining,
      evaluation of the cell surface phosphatidylserine (PS) expression through annexin
      V/PI technique and, the formation of DNA ladder. Down regulation of survivin was
      evaluated in protein level after cell treatment with 4t-CHQB using western
      blotting method. Molecular modeling experiments involving 4t-CHQB binding site of
      survivin showed several strong hydrogen bonds and hydrophobic interactions
      between many important amino acid residues. Overall, the obtained data suggest
      that the assessed spiroquinazolinone benzamide compounds may provide a novel
      therapeutic approach for further evaluation, as an effective chemotherapeutic
      family acting through down regulation of survivin and apoptosis induction in
      breast cancer.

PMID- 27713000
TI  - Overlapping effects of age on associative memory and the anterior hippocampus
      from middle to older age.
AB  - The anterior hippocampus has been implicated in associative memory, and along
      with hippocampal volume, this type of memory declines with age. However, few
      cross-sectional studies include middle-aged samples, making it unclear at what
      point these age-related changes occur. In addition, although men and women have
      been shown to differ in associative memory and rates of age-related hippocampal
      atrophy, sex-differences in aging are rarely studied. To address these issues, we
      assessed memory for word-pairs, hippocampal volume and activation during encoding
      and retrieval, across middle-aged (n=39) and older (n=44) participants,
      specifically in relation to sex. Older adults showed significantly poorer
      associative memory compared to middle-aged adults, paralleled by smaller anterior
      hippocampi and less activation during successful retrieval. The age-by-sex
      interaction observed in memory performance was also mirrored in the volume and
      activation of the hippocampus, indicating more pronounced age-effects in men as
      compared to women. These results indicate a specific role of the anterior
      hippocampus in verbal associative memory and suggest they both decline between
      middle-age and older age.

PMID- 27712998
TI  - Inhibitors of retrograde trafficking active against ricin and Shiga toxins also
      protect cells from several viruses, Leishmania and Chlamydiales.
AB  - Medical countermeasures to treat biothreat agent infections require broad
      spectrum therapeutics that do not induce agent resistance. A cell-based high
      throughput screen (HTS) against ricin toxin combined with hit optimization
      allowed selection of a family of compounds that meet these requirements. The hit
      compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in
      mice even at high doses. Moreover, Retro-2 is an inhibitor of retrograde
      transport that affects syntaxin-5-dependent toxins and pathogens. As a
      consequence, it has a broad-spectrum activity that has been demonstrated both in
      vitro and in vivo against ricin, Shiga toxin-producing O104:H4 entero-hemorrhagic
      E. coli and Leishmania sp. and in vitro against Ebola, Marburg and poxviruses and
      Chlamydiales. An effect is anticipated on other toxins or pathogens that use
      retrograde trafficking and syntaxin-5. Since Retro-2 targets cell components of
      the host and not directly the pathogen, no selection of resistant pathogens is
      expected. These lead compounds need now to be developed as drugs for human use.

PMID- 27713001
TI  - Levo-tetrahydropalmatine inhibits the acquisition of ketamine-induced conditioned
      place preference by regulating the expression of ERK and CREB phosphorylation in
      rats.
AB  - Levo-tetrahydropalmatine (l-THP) is an alkaloid purified from the Chinese herbs
      Corydalis and Stephania and has been used in many traditional Chinese herbal
      preparations for its sedative, analgesic and hypnotic properties. Previous
      studies demonstrated that l-THP has antagonistic activity on dopamine receptors;
      thus, it may have potential therapeutic effects on drug abuse. However, whether l
      THP affects ketamine-induced conditioned place preference (CPP) remains unclear.
      Therefore, the present study was designed to evaluate the effects of l-THP on the
      rewarding behavior of ketamine through CPP. Results revealed that ketamine (5, 10
      and 15mg/kg) induced CPP in rats. Furthermore, Ketamine (10mg/kg) promoted the
      phosphorylation of extracellular-regulated kinase (ERK) and cAMP responsive
      element binding protein (CREB) in the hippocampus (Hip) and caudate putamen
      (CPu), but not in the prefrontal cortex (PFc). l-THP (20mg/kg) co-administered
      with ketamine during conditioning inhibited the acquisition of ketamine-induced
      CPP in rats. Furthermore, l-THP (20mg/kg) prevented the enhanced phosphorylation
      of ERK and CREB in CPu and Hip. These results suggest that l-THP has potential
      therapeutic effects on ketamine-induced CPP. The underlying molecular mechanism
      may be related to its inhibitory effect on ERK and CREB phosphorylation in Hip
      and CPu. The present data supports the potential use of l-THP for the treatment
      of ketamine addiction.

PMID- 27713002
TI  - Sex differences in angiotensin II responses contribute to a differential
      regulation of cox-mediated vascular dysfunction during aging.
AB  - Aging is a cardiovascular risk factor partially related to activation of the
      Renin-Angiotensin System (RAS). RAS activation is also influenced by sex. In this
      regard, our study aims to determine whether sex-associated differences in RAS
      contribute to a differential regulation of vascular aging and associated
      dysfunction. Male and female outbreed CD-1 mice were studied at 3 and 12months of
      age (M). Contribution of RAS was determined by treating mice from 3M to 12M with
      the AngII type 1 receptor blocker losartan (0.6g/L in the drinking water). At
      12M, contractions to AngII were higher in males compared to females (P<0.05).
      This effect was paralleled by a decrease in AngII type 2 receptors in 12M males.
      Aging also diminished ACh relaxation in males, but did not modify female
      responses. Treatment of aortas with indomethacin (10MUM) restored the impaired
      endothelium-dependent relaxation in 12M males, suggesting an increase of
      cyclooxygenase (COX)-derived vasoconstrictors in aged males. Chronic treatment of
      mice with losartan also improved endothelium-dependent relaxation. Besides,
      losartan significantly decreased COX-2 expression and activity in 12M male, with
      a minor effect in aged females. Aging increases AngII contraction and induces
      endothelial dysfunction differently in males and females. In aged males, RAS
      contributed to increased COX-2 expression and activity, which in turn may lead to
      vascular dysfunction.

PMID- 27713003
TI  - Diacylglycerol kinase epsilon suppresses expression of p53 and glycerol kinase in
      mouse embryo fibroblasts.
AB  - The incorporation of glycerol into lipid was measured using SV40 transformed
      mouse embryo fibroblasts (MEFs) from either wild-type (WT) mice or from mice in
      which the epsilon isoform of diacylglycerol kinase (DGKepsilon) was knocked out
      (DGKepsilon-/-). We present an explanation for our finding that DGKepsilon-/-
      MEFs exhibited greater uptake of 3H-glycerol into the cell and a greater
      incorporation into lipids compared with their WT counterparts, with no change in
      the relative amounts of various lipids between the DGKepsilon-/- and WT MEFs.
      Glycerol kinase is more highly expressed in the DGKepsilon-/- cells than in their
      WT counterparts. In addition, the activity of glycerol kinase is greater in the
      DGKepsilon-/- cells than in their WT counterparts. Other substrates that enter
      the cell independent of glycerol kinase, such as pyruvate or acetate, are
      incorporated into lipid to the same extent between DGKepsilon-/- and WT cell
      lines. We also show that expression of p53, a transcription factor that increases
      the synthesis of glycerol kinase, is increased in DGKepsilon-/- MEFs in
      comparison to WT cells. We conclude that the increased incorporation of glycerol
      into lipids in DGKepsilon-/- cells is a consequence of up-regulation of glycerol
      kinase and not a result of an increase in the rate of lipid synthesis.
      Furthermore, increased expression of the pro-survival gene, p53, in cells knocked
      out for DGKepsilon suggests that cells over-expressing DGKepsilon would have a
      greater propensity to become tumorigenic.

PMID- 27713005
TI  - Deep sedation without intubation during second trimester surgical termination in
      an inpatient hospital setting.
AB  - OBJECTIVES: Safety of outpatient dilation and evacuations with intravenous (iv)
      sedation without intubation has been demonstrated, but there is a paucity of data
      on deep iv sedation on an inpatient second trimester surgical termination
      population. The purpose of this study is to evaluate complications of deep
      sedation with propofol without the use of intubation during second trimester
      surgical terminations in an inpatient teaching institution. STUDY DESIGN: A
      retrospective chart review of all obstetrical and anesthetic data from inpatient
      dilation and evacuations between gestational ages 15 0/7 and 24 0/7 during the
      years 2002 to 2015. We examined 332 patient charts. Primary outcomes included
      suspected perioperative pulmonary aspiration and conversion to an intubated
      general anesthesia. RESULTS: No perioperative pulmonary aspiration cases were
      either suspected or confirmed. There were a total of 14 (4.2%) patients that had
      intubation compared to 313 with natural airway (94.3%) or laryngeal mask (1.5%).
      Of the 14 intubated, 9 (64%) were started with intubation, and 5 (36%) were
      converted during the procedure (1.7% of those started with nonintubated
      anesthesia). Cases requiring intubation were associated with longer procedure
      times (p=<0.001), higher American Society of Anesthesiologists (ASA) class
      (p=0.038), greater estimated blood loss (p=<0.001) and a primary indication of
      maternal health (p=<0.001) for the dilation and evacuation. CONCLUSIONS: Deep
      sedation without intubation appears safe in a hospital setting with few
      complications reported. IMPLICATIONS: Deep sedation without intubation for
      operating room dilation and evacuation is a safe option that rarely resulted in
      conversion to intubation and, in most cases, should be the anesthesia method of
      choice at initiation in an inpatient setting.

PMID- 27713006
TI  - Medical exchange with Japan and the UK.

PMID- 27713004
TI  - Biological and pathophysiological roles of end-products of DHA oxidation.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFA) are known to be present and/or
      enriched in vegetable and fish oils. Among fatty acids, n-3 PUFA are generally
      considered to be protective in inflammation-related diseases. The guidelines for
      substituting saturated fatty acids for PUFAs have been highly publicized for
      decades by numerous health organizations. Recently, however, the beneficial
      properties of n-3 PUFA are questioned by detailed analyses of multiple randomized
      controlled clinical trials. The reported heterogeneity of results is likely due
      not only to differential effects of PUFAs on various pathological processes in
      humans, but also to the wide spectrum of PUFA's derived products generated in
      vivo. SCOPE OF REVIEW: The goal of this review is to discuss the studies focused
      on well-defined end-products of PUFAs oxidation, their generation, presence in
      various pathological and physiological conditions, their biological activities
      and known receptors. Carboxyethylpyrrole (CEP), a DHA-derived oxidized product,
      is especially emphasized due to recent data demonstrating its pathophysiological
      significance in many inflammation-associated diseases, including atherosclerosis,
      hyperlipidemia, thrombosis, macular degeneration, and tumor progression. MAJOR
      CONCLUSIONS: CEP is a product of radical-based oxidation of PUFA that forms
      adducts with proteins and lipids in blood and tissues, generating new powerful
      ligands for TLRs and scavenger receptors. The interaction of CEP with these
      receptors affects inflammatory response, angiogenesis, and wound healing. GENERAL
      SIGNIFICANCE: The detailed understanding of CEP-mediated cellular responses may
      provide a basis for the development of novel therapeutic strategies and dietary
      recommendations.

PMID- 27713007
TI  - Injury of the deep femoral artery penetrating branch caused by the breakage of a
      greater trochanter fixed cable: Case report.

PMID- 27713008
TI  - CT-based morphological analysis of spinal fractures in patients with diffuse
      idiopathic skeletal hyperostosis.
AB  - PURPOSE: To clarify correlations between spinal fracture and delayed paralysis in
      patients with diffuse idiopathic skeletal hyperostosis (DISH) using computed
      tomography (CT) with multiplanar reformatting (CT-MPR). DISH increases
      susceptibility to unstable spinal fractures, leading to neurological
      deterioration. The pathomechanism of the neurological injury is unclear. METHODS:
      This multicenter retrospective study included 42 DISH patients (32 male; 10
      female) treated for 45 spinal fractures during a 5-year period. The mean age at
      the time of injury was 77.1 +/- 10.1 years. The cause of injury, delay in
      diagnosis, fracture location, and neurological status were recorded, and anterior
      and posterior-column fractures, a fracture displacement over 3 mm, and posterior
      column ankylosis were assessed using CT-MPR. RESULTS: Most fractures (73.8%)
      resulted from trivial trauma, such as falling from a standing or sitting
      position. Diagnosis was delayed in 47.6% of the patients, primarily due to delays
      in seeking medical attention (65.0%). Although 78.6% of the patients were
      neurologically intact at the time of injury, 54.8% developed paralysis, defined
      by a change in one or more Frankel-score levels during short-term follow-up. Of
      the fractures, 39.1% were in the vertebral body, and 60.9% were at the disc
      level. Fractures with posterior-column ankylosis were significantly associated
      with delayed paralysis. CONCLUSIONS: CT-MPR was useful for evaluating spinal
      fractures and determining treatment in patients with DISH. Fractures associated
      with posterior-column ankylosis resulted in unstable three-column injuries that
      led to delayed neurological deterioration. Early surgical stabilization of such
      fractures is recommended to avoid delayed paralysis.

PMID- 27713009
TI  - Cervical spinal canal stenosis first presenting after spinal cord injury due to
      minor trauma: An insight into the value of preventive decompression.
AB  - PURPOSE: Patients with pre-existing cervical spinal canal stenosis (CSCS) may
      have minimal or no symptoms. However, performing preventive decompression is
      controversial as the incidence of CSCS leading to severe cord injury is unknown.
      Hence, this study aims to revisit the threshold for surgery in "silent" CSCS by
      reviewing the neurologic outcomes of patients with undiagnosed CSCS who sustained
      a cervical spinal cord injury (CSCI). METHODS: Two groups of subjects were
      recruited for analysis. Firstly, patients with trauma-induced CSCI without
      fracture or dislocation were included. Pre-existing CSCS was diagnosed by MRI
      measurements. The second group consisted of asymptomatic subjects recruited from
      the general population who also had MRIs performed. Canal sizes were compared
      between this control group and the patient group. Within the patient group,
      neurological assessments and outcomes by Frankel classification were performed in
      patients treated surgically or conservatively. RESULTS: 32 patients with CSCS
      were recruited. The mean spinal canal sagittal diameter (disc-level) of all CSCS
      cases was 5.3 +/- 1.4 mm (1.3-8.2). In comparison, the diameter was 10.5 +/- 1.7
      mm (6.6-14.6) in the 47 asymptomatic individuals recruited from the general
      population. Decompression was performed in 17 patients and conservative treatment
      in 15. Mean follow-up was 19.3 +/- 17.0 months (6-84). At the final follow-up, 3
      patients (9.3%) returned to their pre-injury Frankel grade, whereas 26 patients
      (83.3%) lost one or more neurological grade. Three patients (9.3%) died.
      CONCLUSIONS: Majority of patients with "silent" CSCS who sustained cervical cord
      injuries did not return to their pre-injury neurological status. All of these
      subjects have pre-existing canal stenosis hence the risk of cord injury. Given
      the poor neurological outcome of CSCS, a lower threshold for surgery could be
      indicated to avoid these disastrous injuries. However, before making any
      conclusive recommendation we must first identify the prevalence of "silent" CSCS
      in the general population and the risk of developing spinal cord injury with more
      prospective population-based studies.

PMID- 27713010
TI  - Phosphorylated Codonopsis pilosula polysaccharide could inhibit the virulence of
      duck hepatitis A virus compared with Codonopsis pilosula polysaccharide.
AB  - To screen effective anti-duck hepatitis A virus (DHAV) drugs, we applied STMP
      STPP method to prepare phosphorylated Codonopsis pilosula polysaccharide (pCPPS),
      the phosphorylation-modified product of Codonopsis pilosula polysaccharide
      (CPPS). The IR spectrum and field emission scanning electron microscope (FE-SEM)
      were subsequently used to analyze the structure of pCPPS. Several tests were
      conducted to compare the anti-DHAV activities of CPPS and pCPPS. The MTT method
      was used to compare the effect of the drugs on DHAV-infected duck embryonic
      hepatocytes (DEHs), and the Reed-Muench assay was employed to observe changes in
      the virulence of DHAV. We also applied real-time PCR to examine the relationship
      between virus replication and the expression of IFN-beta. The results indicated
      that CPPS could not inhibit the replication of DHAV. In contrast, pCPPS increased
      the virus TCID50, inhibited viral replication and, accordingly, increased the
      survival rate of DEHs infected with DHAV. Because DHAV induced the expression of
      IFN-beta, and the IFN-beta expression level was positively associated with the
      number of DHAV, the reduction of IFN-beta expression levels after pCPPS treatment
      demonstrated a decrease in the number of virus particles. These results indicated
      that pCPPS, which reduces the number of DHAV, was more effective than CPPS in
      anti-DHAV activity.

PMID- 27713011
TI  - The influence of metal ions on the dielectric enhancement and radical generation
      of rice starch during microwave processing.
AB  - In this study, the effect of the enrichment of rice starch with metal ions on its
      capability to generate free radicals during microwave processing was
      investigated. The underlying mechanism was explored from two aspects: dielectric
      and thermal properties. Rice starch was modified with ions of iron, copper,
      manganese and calcium. The modified starches were analyzed in terms of dielectric
      properties, activation energy (Ea) and thermodynamic characteristics of
      gelatinization. The quantity and character of the free radicals were analyzed
      using electron paramagnetic resonance (EPR). The results showed that the metal
      ions could change the dielectric property and inter structure of rice starch,
      thus influencing the ability of rice starch to generate radicals under microwave
      irradiation.

PMID- 27713012
TI  - Forebrain neurone-specific deletion of insulin-regulated aminopeptidase causes
      age related deficits in memory.
AB  - Central infusion of Insulin-Regulated Aminopeptidase (IRAP) inhibitors improves
      memory in both normal rodents and in models of memory deficit. However, in
      contrast, the global IRAP knockout mice (KO) demonstrate age-accelerated spatial
      memory deficits and no improvements in performance in any memory tasks.
      Potentially, the observed memory deficit could be due to the absence of IRAP in
      the developing brain. We therefore generated a postnatal forebrain neuron
      specific IRAP knockout mouse line (CamKIIalphaCre; IRAPlox/lox). Unexpectedly, we
      demonstrated that postnatal deletion of IRAP in the brain results in significant
      deficits in both spatial reference and object recognition memory at three months
      of age, although spatial working memory remained intact. These results indicate a
      significant role for IRAP in postnatal brain development and normal function of
      the hippocampus in adulthood.

PMID- 27713014
TI  - Synthesis and biological evaluation of furocoumarin derivatives on melanin
      synthesis in murine B16 cells for the treatment of vitiligo.
AB  - Furocoumarins, isolated from Psoralen corylifolia L., were found to be the most
      effective drug in the treatment of vitiligo nowadays. Twenty-five furocoumarin
      derivatives were thus designed and synthesized in order to improve the
      melanogenesis in B16 cells for the first time. Among them, twenty-three compounds
      were more potent than the positive control (8-MOP), the commonly used drug for
      vitiligo in clinic. Noticeably, compounds 6m (350.5%) and 6p (313.1%) based on
      the scaffold of 6k (2H-benzofuro[2,3-h]chromen-2-one) were nearly 3-fold stronger
      than 8-MOP (114.50%). The in vitro melanin synthesis evaluation of these
      structurally diverse analogues had also led to an outline of structure-activity
      relationship.

PMID- 27713013
TI  - Synthesis, photophysical properties and biological evaluation of beta
      alkylaminoporphyrin for photodynamic therapy.
AB  - A series of beta-alkylaminoporphyrins conjugated with different amines at beta
      position (D1-D3) or with electron-donating and electron-withdrawing substituents
      at phenyl position (D4-D6) were synthesized. Their photophysical and
      photochemical properties, intracellular localization, photocytotoxicities in
      vitro and vivo were also investigated. All target compounds exhibited no
      cytotoxicities in the dark and excellent photocytotoxicities against HeLa cells.
      Among them, D6 showed the highest phototoxicity and the lowest dark toxicity,
      which was more phototoxic than Hematoporphyrin monomethyl ether (HMME). In
      addition, D6 exhibited best photodynamic antitumor efficacy on BALB/c nude mice
      bearing HeLa tumor. Therefore, D6 is a powerful and promising antitumor
      photosensitizer for photodynamic therapy.

PMID- 27713015
TI  - In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors.
AB  - Herein we report the synthesis, PDE-4B and TNF-alpha inhibitory activities of a
      few dibenzo[b,d]furan-1-yl-thiazole derivatives. The hydroxycyclohexanol amide
      derivatives 14, 18, 24, 29, 31 and 33 exhibited promising in vitro PDE-4B and TNF
      alpha inhibitory activities. Compound 24 showed good systemic availability in
      preclinical animal models and was also found to be non-toxic (exploratory
      mutagenicity test). Further it exhibited promising results in in vivo asthma/COPD
      and Uveitis models.

PMID- 27713016
TI  - A cell-based approach to characterize antimicrobial compounds through kinetic
      dose response.
AB  - The rapid spread of antibiotic resistance has created a pressing need for the
      development of novel drug screening platforms. Herein, we report on the use of
      cell-based kinetic dose response curves for small molecule characterization in
      antibiotic discovery efforts. Kinetically monitoring bacterial growth at sub
      inhibitory concentrations of antimicrobial small molecules generates unique dose
      response profiles. We show that clustering of profiles by growth characteristics
      can classify antibiotics by mechanism of action. Furthermore, changes in growth
      kinetics have the potential to offer insight into the mechanistic action of novel
      molecules and can be used to predict off-target effects generated through
      structure-activity relationship studies. Kinetic dose response also allows for
      detection of unstable compounds early in the lead development process. We propose
      that this kinetic approach is a rapid and cost-effective means to gather critical
      information on antimicrobial small molecules during the hit selection and lead
      development pipeline.

PMID- 27713017
TI  - Purification and characterization of d-allulose 3-epimerase derived from
      Arthrobacter globiformis M30, a GRAS microorganism.
AB  - An enzyme that catalyzes C-3 epimerization between d-fructose and d-allulose was
      found in Arthrobacter globiformis strain M30. Arthrobacter species have long been
      used in the food industry and are well-known for their high degree of safety. The
      enzyme was purified by ion exchange and hydrophobic interaction chromatographies
      and characterized as a d-allulose 3-epimerase (d-AE). The molecular weight of the
      purified enzyme was estimated to be 128 kDa with four identical subunits. The
      enzyme showed maximal activity and thermostability in the presence of Mg2+. The
      optimal pH and temperature for enzymatic activity were 7.0-8.0 and 70 degrees C,
      respectively. The enzyme was immobilized to ion exchange resin whereupon it was
      stable for longer periods than the free enzyme when stored at below 10 degrees C.
      In the column reaction, the enzyme activity also maintained stability for more
      than 4 months. Under these conditions, 215 kg of d-allulose produced per liter
      immobilized enzyme, and this was the highest production yield of d-allulose
      reported so far. These highly stable properties suggest that this enzyme
      represents an ideal candidate for the industrial production of d-allulose.

PMID- 27713018
TI  - Use of phylogenetical analysis to predict susceptibility of pathogenic Candida
      spp. to antifungal drugs.
AB  - Successful treatment of a Candida infection relies on 1) an accurate
      identification of the pathogenic fungus and 2) on its susceptibility to
      antifungal drugs. In the present study we investigated the level of correlation
      between phylogenetical evolution and susceptibility of pathogenic Candida spp. to
      antifungal drugs. For this, we compared a phylogenetic tree, assembled with the
      concatenated sequences (2475-bp) of the ATP2, TEF1, and TUF1 genes from 20
      representative Candida species, with published minimal inhibitory concentrations
      (MIC) of the four principal antifungal drug classes commonly used in the
      treatment of candidiasis: polyenes, triazoles, nucleoside analogues, and
      echinocandins. The phylogenetic tree revealed three distinct phylogenetic
      clusters among Candida species. Species within a given phylogenetic cluster have
      generally similar susceptibility profiles to antifungal drugs and species within
      Clusters II and III were less sensitive to antifungal drugs than Cluster I
      species. These results showed that phylogenetical relationship between clusters
      and susceptibility to several antifungal drugs could be used to guide therapy
      when only species identification is available prior to information pertaining to
      its resistance profile. An extended study comprising a large panel of clinical
      samples should be conducted to confirm the efficiency of this approach in the
      treatment of candidiasis.

PMID- 27713019
TI  - Galleria mellonella hemocytes: A novel phagocytic assay for Leishmania (Viannia)
      braziliensis.
AB  - Galleria mellonella is an excellent invertebrate model for the study of diseases
      that involve interactions with cells from the innate immune system, since they
      have an innate immune system capable of recognizing the pathogens. Here we
      present for the first time, an alternative model for an in vitro phagocytic assay
      using hemocytes of G. mellonella larvae to study infection by Leishmania
      (Viannia) braziliensis. We showed that the insect phagocytic cells were able to
      engulf promastigotes. Furthermore, this infective form differentiated into the
      amastigote form inside those cells. However, the cells in this model seem
      resistant to the parasite, since amastigotes were depleted after 24h and NO
      levels were maintained after infection. Our model opens an avenue of
      possibilities for new investigations regarding other Leishmania species,
      mechanisms of invasion and evasion, receptors involved, release of signaling
      molecules and, above all, it is a novel infection model using invertebrate
      animals.

PMID- 27713020
TI  - Evaluation of urine for Leishmania infantum DNA detection by real-time
      quantitative PCR.
AB  - The availability of some sorts of biological samples which require noninvasive
      collection methods has led to an even greater interest in applying molecular
      biology on visceral leishmaniasis (VL) diagnosis, since these samples increase
      the safety and comfort of both patients and health professionals. In this
      context, this work aimed to evaluate the suitability of the urine as a specimen
      for Leishmania infantum kinetoplast DNA detection by real-time quantitative PCR
      (qPCR). Subsequent to the reproducibility analysis, the detection limit of the
      qPCR assay was set at 5fg (~0.025 parasites) per MUL of urine. From the
      comparative analysis performed with a set of diagnostic criteria (serological and
      molecular reference tests), concordance value of 96.08% was obtained (VL
      suspected and HIV/AIDS patients, n=51) (P>0.05). Kappa coefficient (95% CI)
      indicated a good agreement between the test and the set of diagnostic criteria
      (k=0.778+/-0.151). The detection of Leishmania DNA in urine by qPCR was possible
      in untreated individuals, and in those with or without suggestive renal
      impairment. Fast depletion of the parasite's DNA in urine after treatment (from
      one dose of meglumine antimoniate) was suggested by negative qPCR results, thus
      indicating it as a potential alternative specimen to follow up the efficacy of
      therapeutic approaches. Even when evaluated in a clinically heterogeneous set of
      patients, the urine showed good prospect as sample for VL diagnosis by qPCR, also
      indicating a good negative predictive value for untreated suspected patients.

PMID- 27713021
TI  - Disodium cromoglycate inhibits asthma-like features induced by sphingosine-1
      phosphate.
AB  - Compelling evidence suggests the involvement of sphingosine-1-phosphate (S1P) in
      the pathogenesis of asthma. The systemic administration of S1P causes asthma like
      features in the mouse involving mast cells. In this study we investigated whether
      disodium cromoglycate (DSCG), administered as a preventative treatment as in
      human therapy, could affect S1P effects on airways. BALB/c mice, treated with
      DSCG, received subcutaneous administration of S1P. Bronchi and pulmonary tissues
      were collected and functional, molecular and cellular studies were performed.
      DSCG inhibited S1P-induced airway hyper-reactivity as well as pulmonary
      inflammation. DSCG decreased the recruitment of solely mast cells and B cells in
      the lung. IgE serum levels, prostaglandin D2, mucus production and IL-13 were
      also reduced when mice were pretreated with DSCG. S1P induced pulmonary
      expression of CD23 on T and B cells, that was reversed by DSCG. Conversely, S1P
      failed to upregulate CD23 in mast cell-deficient Kit W-sh/W-sh mice. In
      conclusion we have shown that DSCG inhibits S1P-induced asthma like features in
      the mouse. This beneficial effect is due to a regulatory action on mast cell
      activity, and in turn to an inhibition of IgE-dependent T and B cells responses.

PMID- 27713022
TI  - The underappreciated in vitro activity of tedizolid against Bacteroides fragilis
      species, including strains resistant to metronidazole and carbapenems.
AB  - Because Bacteroides fragilis has the ability to develop mechanisms of resistance
      to almost all antibiotics, we studied the comparative in vitro activity of
      tedizolid against 124 Bacteroides group species clinical isolates, including
      carbapenem, metronidazole and piperacillin-tazobactam resistant strains.
      Tedizolid had an MIC90 of 2 MUg/ml (range, 0.5-4 MUg/ml) and was 1-4 times more
      active than linezolid that had an MIC90 of 8 MUg/ml (range, 2-16 MUg/ml). It was
      also active (MICs 0.5-2 MUg/ml) against the 27 ertapenem, 2 metronidazole and 12
      piperacillin-tazobactam resistant strains tested. This suggests that tedizolid
      may be useful treating infections, including bacteremias, due to resistant B.
      fragilis group species, as well as, mixed skin and soft tissue infections such as
      diabetic foot infections caused by Gram-positive aerobes and B. fragilis group
      species.

PMID- 27713023
TI  - Development of a screening tool to prioritize testing for the carcinogenic hazard
      of residual aromatic extracts and related petroleum streams.
AB  - Residual aromatic extracts (RAE) are petroleum substances with variable
      composition predominantly containing aromatic hydrocarbons with carbon numbers
      greater than C25. Because of the high boiling nature of RAEs, the aromatics
      present are high molecular weight, with most above the range of carcinogenic
      polycyclic aromatic hydrocarbons (PAHs). However, refinery distillations are
      imperfect; some PAHs and their heteroatom-containing analogs (collectively
      referred to as polycyclic aromatic content or PAC) may remain in the parent
      stream and be extracted into the RAE, and overall PAC content is related to the
      carcinogenic potential of an RAE. We describe here a real-time analytical
      chemistry-based tool to assess the carcinogenic hazard of RAE via the development
      of a functional relationship between carcinogenicity and boiling point. Samples
      representative of steps along the RAE manufacturing process were obtained from
      five refineries to evaluate relationships between mutagenicity index (MI), PAC
      ring content and gas chromatographic distillation (GCD) curves. As expected, a
      positive linear relationship between MI and PAC ring content occurred, most
      specifically for 3-6 ring PAC (R2=0.68). A negative correlation was found between
      MI and temperature at 5% vaporization by GCD (R2=0.72), indicating that samples
      with greater amounts of lower boiling constituents were more likely to be
      carcinogenic. The inverse relationship between boiling range and carcinogenicity
      was further demonstrated by fractionation of select RAE samples (MI=0.50+0.07;
      PAC=1.70+0.51wt%; n=5) into low and high boiling fractions, where lower boiling
      fractions were both more carcinogenic than the higher boiling fractions
      (MI=2.36+/-0.55 and 0.17+/-0.11, respectively) and enriched in 3-6 ring PACs
      (5.20+0.70wt% and 0.97+0.35wt%, respectively). The criteria defining
      carcinogenicity was established as 479 degrees C for the 5% vaporization points
      by GCD, with an approximate 95% probability of a future sample having an MI below
      the recommended limit of 0.4 for RAEs. Overall, these results provide a cost
      efficient and real-time tool by which the carcinogenic potential of RAEs can be
      assessed at the refinery level, ultimately providing a means to readily monitor
      and minimize the carcinogenic potential of RAEs.

PMID- 27713024
TI  - MicroRNA-877-5p is involved in the trovafloxacin-induced liver injury.
AB  - Trovafloxacin develops severe hepatotoxicity; however, the underlying mechanism
      of the trovafloxacin-induced liver injury has not been cleared. It has been shown
      that microRNAs (miRNAs) can be involved in the development of drug-induced liver
      injuries. We performed a miRNA microarray analysis to identify hepatic miRNAs
      that were induced or reduced by trovafloxacin in mice. It was demonstrated that
      miR-877-5p was the most increased miRNA in the mouse liver 24h after the
      trovafloxacin administration. To investigate the role of miR-877-5p in the liver,
      we established miR-877-5p-overexpressed HepG2 cells. Microarray analysis detected
      altered expressions in 2077 (>2-fold) and 1547 (<0.5-fold) genes in the miR-877
      5p overexpressing cells compared to the mock cells. Especially, SLCO4C1, PEPCK,
      MT1M, HIST1H2BM, LGI1, and PLA2G2A were markedly increased or decreased in the
      miR-877-5p overexpressing cells. We conducted a correlation analysis between the
      expression levels of miR-877-5p and the six genes in eight miR-877-5p stably
      expressed clones. It was shown that the PEPCK expression levels were correlated
      with miR-877-5p expression levels. PEPCK is associated with development of
      apoptotic cell death; therefore, the increased miR- 877-5p-induced PEPCK can be a
      trigger that is involved in the development of trovafloxacin-induced liver
      injury.

PMID- 27713025
TI  - Event related potentials changes associated with the processing of auditory valid
      and invalid targets as a function of previous trial validity in a Posner's
      paradigm.
AB  - The present study tries to analyze the neural basis of the so-called "Inter-trial
      Validity-Invalidity Effects" by means of Event-Related Potentials. The N1, P2,
      P3a and P3b components were examined. The aim is to show the sequential effects
      on Event-Related Potentials by analyzing the effect of previous trial condition
      (n-1) in the processing of current trial target (n). Event-Related Potentials
      results indicate that the N1 and P2 components show higher negativity in valid
      trials preceded by invalid trials with respect to valid trials preceded by valid
      trials, elicited by the so-called "Processing Negativity". Next, the P3a and P3b
      components show increased positivity in invalid trials preceded by valid trials
      compared to invalid trials preceded by invalid trials. Present results suggest
      that there is a dynamic updating of attentional resources and working memory, due
      to the influence of previous trial condition (n-1) on the current trial
      processing (n). This dynamic updating would be higher after trial validity
      changes, and it would be compatible with the Bayesian Brain Model.

PMID- 27713026
TI  - Agents that activate the High Osmolarity Glycerol pathway as a means to combat
      pathogenic molds.
AB  - Treatment of invasive fungal infections often fails due to the limited number of
      therapeutic options. In this study, we have analyzed the impact of agents
      activating the High Osmolarity Glycerol (HOG) pathway on molds that cause
      infections in humans and livestock. We found that agents like fludioxonil and
      iprodione, have a clear anti-fungal activity against pathogenic Aspergillus,
      Lichtheimia, Rhizopus and Scedosporium species. Only A. terreus turned out to be
      resistant to fludioxonil, even though it is sensitive to iprodione and able to
      adapt to hyperosmotic conditions. Moreover, the A. terreus tcsC gene can fully
      complement an A. fumigatus DeltatcsC mutant, thereby also restoring its
      sensitivity to fludioxonil. The particular phenotype of A. terreus is therefore
      likely to be independent of its TcsC kinase. In a second part of this study, we
      further explored the impact of fludioxonil using A. fumigatus as a model
      organism. When applied in concentrations of 1-2MUg/ml, fludioxonil causes an
      immediate growth arrest and, after longer exposure, a quantitative killing.
      Hyphae respond to fludioxonil by the formation of new septa and closure of nearly
      all septal pores. Mitosis occurs in all compartments and is accompanied by a re
      localization of the NimA kinase to the cytoplasm. In the swollen compartments,
      the massive extension of the cell wall triggers a substantial reorganization
      resulting in an enhanced incorporation of chitin and, most strikingly, a massive
      loss of galactomannan. Hence, HOG-activating agents have dramatic cell biological
      consequences and may represent a valuable, future element in the armory that can
      be used to combat mold infections.

PMID- 27713027
TI  - The secretome of Acinetobacter baumannii ATCC 17978 type II secretion system
      reveals a novel plasmid encoded phospholipase that could be implicated in lung
      colonization.
AB  - Acinetobacter baumannii infections are compounded with a striking lack of
      treatment options. In many Gram-negative bacteria, secreted proteins play an
      important early role in avoiding host defences. Typically, these proteins are
      targeted to the external environment or into host cells using dedicated transport
      systems. Despite the fact that medically relevant species of Acinetobacter
      possess a type II secretion system (T2SS), only recently, its significance as an
      important pathway for delivering virulence factors has gained attention. Using in
      silico analysis to characterize the genetic determinants of the T2SS, which are
      found clustered in other organisms, in Acinetobacter species, they appear to have
      a unique genetic organization and are distributed throughout the genome. When
      compared to other T2SS orthologs, individual components of the T2SS apparatus
      showed the highest similarity to those of Pseudomonas aeruginosa. A mutant of
      Acinetobacter baumannii strain ATCC 17978 lacking the secretin component of the
      T2SS (DeltagspD), together with a trans-complemented mutant, were tested in a
      series of in vitro and in vivo assays to determine the role of T2SS in
      pathogenicity. The DeltagspD mutant displayed decreased lipolytic activity,
      associated with attenuated colonization ability in a murine pneumonia model.
      These phenotypes are linked to LipAN, a novel plasmid-encoded phospholipase,
      identified through mass spectroscopy as a T2SS substrate. Recombinant LipAN
      showed specific phospholipase activity in vitro. Proteomics on the T2-dependent
      secretome of ATCC 17978 strain revealed its potential dedication to the secretion
      of a number of lipolytic enzymes, among others which could contribute to its
      virulence. This study highlights the role of T2SS as an active contributor to the
      virulence of A. baumannii potentially through secretion of a newly identified
      phospholipase.

PMID- 27713028
TI  - Colistin-entrapped liposomes driven by the electrostatic interaction: Mechanism
      of drug loading and in vivo characterization.
AB  - The potential in vivo application of liposome for polycationic colistin has been
      hindered by the poor entrapment efficiency (EE) due to their phospholipid
      membrane permeability. The objective of this study is to investigate the loading
      mechanism and validity of applying electrostatic attraction for the colistin
      entrapment and delivery in liposomes. Anionic lipids with various structures were
      used for colistin entrapment, and the properties of resulting liposomes (i.e.
      zeta-potential, EE and release rate) were highly dependent on the structure of
      anionic lipids. Based on consideration of intermolecular interactions, the
      retention of electrostatically entrapped colistin is essentially determined by
      the balance of interfacial hydrophobic attraction and electrostatic repulsion.
      The liposomal colistin showed the reduced bacterial killing rate, but did not
      compromise the in vitro antibacterial activity. Specially, the PEGylated
      liposomal colistin of sodium cholesteryl sulfate (Chol-SO4-) showed the best drug
      retention, resulting in the significantly increased maximum-tolerated dose,
      prolonged blood circulation and decreased colistin distribution in kidney after
      intravenous administration in mice. These results highlight the potential utility
      of electrostatically entrapped liposome for polycationic colistin delivery.

PMID- 27713029
TI  - Colon targeted oral drug delivery system based on alginate-chitosan microspheres
      loaded with icariin in the treatment of ulcerative colitis.
AB  - In recent years, oral colon specific drug delivery system has been paid more
      attention in the treatment of inflammatory bowel disease (IBD). As the special pH
      condition in gastrointestinal tract, the challenge for treatment of IBD was that
      the colon drug delivery system should endure the low pH in stomach and release
      drugs quickly in high pH in colon. Icariin with the poor solubility and low
      bioavailability limited the treatment of many diseases in clinic. In this study,
      the protective mechanism of alginate-chitosan microspheres loaded with icariin
      were investigated with trinitrobenzene sulfonic acid (TNBS)/ethanol induced
      colonic mucosal injury in rats. The results of drug release showed that the
      icariin loaded into microspheres released only 10% in simulated gastric fluid and
      a high amount of 65.6% released in simulated colonic fluid. The fluorescence
      tracer indicated high retention of targeted microspheres more than 12h in colon.
      The microspheres loaded with icariin could not only reduce the colonic injury by
      decreasing the colon mucosa damage index in rats, but also reduce the
      inflammatory response by reducing the production and gene expression of
      inflammatory mediators and cytokines in colonic mucosa. All the results indicate
      that targeted microspheres loaded with icariin could exert the colon-protective
      effects through reducing the inflammatory response, which would be developed as a
      potential drug controlled release system for treatment of ulcerative colitis.

PMID- 27713031
TI  - Agammaglobulinemia associated to nasal polyposis due to a hypomorphic RAG1
      mutation in a 12 years old boy.
AB  - Recombination-activating gene (RAG) 1 and 2 mutations in humans cause T- B- NK+
      SCID and Omenn syndrome, but milder phenotypes associated with residual protein
      activity have been recently described. We report a male patient with a diagnosis
      of common variable immunodeficiency (CVID) born from non-consanguineous parents,
      whose immunological phenotype was characterized by severe reduction of B cells
      and agammaglobulinemia for which several candidate genes were excluded by
      targeted Sanger sequencing. Next Generation Sequencing revealed two compound
      heterozygous mutations in the RAG1 gene: the previously described p.R624H, and
      the novel p.Y728H mutation, as well as the known polymorphism p.H249R. This case
      reinforces the notion of large phenotypic spectrum in RAG deficiency and opens
      questions on the management and follow-up of these patients.

PMID- 27713032
TI  - Re: A Trial of Shuangbai San for Treating Primary Liver Cancer Patients With
      Cancer Pain.

PMID- 27713030
TI  - Role of the JAK/STAT signaling pathway in regulation of innate immunity in
      neuroinflammatory diseases.
AB  - The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT)
      signaling pathway is utilized by numerous cytokines and interferons, and is
      essential for the development and function of both innate and adaptive immunity.
      Aberrant activation of the JAK/STAT pathway is evident in neuroinflammatory
      diseases such as Multiple Sclerosis and Parkinson's Disease. Innate immunity is
      the front line defender of the immune system and is composed of various cell
      types, including microglia, macrophages and neutrophils. Innate immune responses
      have both pathogenic and protective roles in neuroinflammation, depending on
      disease context and the microenvironment in the central nervous system. In this
      review, we discuss the role of innate immunity in the pathogenesis of
      neuroinflammatory diseases, how the JAK/STAT signaling pathway regulates the
      innate immune response, and finally, the potential for ameliorating
      neuroinflammation by utilization of JAK/STAT inhibitors.

PMID- 27713033
TI  - A 10-Year Longitudinal Study of Effects of a Multifaceted Residency Spiritual
      Care Curriculum: Clinical Ability, Professional Formation, End of Life, and
      Culture.
AB  - CONTEXT: Although spiritual care (SC) is recognized as important in whole-person
      medicine, physicians infrequently address patients' spiritual needs, citing lack
      of training. Although many SC curricula descriptions exist, few studies report
      effects on physicians. OBJECTIVES: To broadly examine immediate and long-term
      effects of a required, longitudinal, residency SC curriculum, which emphasized
      inclusive patient-centered SC, compassion, and spiritual self-care. METHODS: We
      conducted in-depth individual interviews with 26 physicians (13 intervention; 13
      comparison) trained at a 13-13-13 residency. We interviewed intervention
      physicians three times over 10 years-1) preintervention, as PGY1s, 2)
      postintervention, as PGY3s, 3) eight-year postintervention, as practicing
      physicians. We interviewed comparison physicians as PGY3s. Interviews were audio
      recorded, transcribed, and analyzed by four researchers. RESULTS: Forty-nine
      interviews were analyzed. General: Both groups were diverse regarding personal
      importance of spirituality/religion. All physicians endorsed the value of SC,
      sharing rich patient stories particularly related to end of life and cultural
      diversity. Curricular effects: 1) skills/barriers-intervention physicians
      demonstrated progressive improvements in clinical approach, accompanied by
      diminishing worries related to SC. PGY3 comparison physicians struggled with SC
      skills and worries more than PGY3 intervention physicians, 2) physician formation
      most physicians described residency as profoundly challenging and transformative.
      Even after eight years, many intervention physicians noted that reflection on
      their diverse beliefs and values in safety, coupled with compassion shown to them
      through this curriculum, had deeply positive effects. High impact training:
      patient-centered spiritual assessment; chaplain rounds; spiritual self-care
      workshop/retreats; multicultural SC framework. CONCLUSION: A longitudinal,
      multifaceted residency SC curriculum can have lasting positive effects on
      physicians' SC skills and their professional/personal formation.

PMID- 27713034
TI  - A Matter of Time: The Case of a Patient With a Left Ventricular Assist Device.

PMID- 27713035
TI  - In vivo fate of lipid-based nanoparticles.
AB  - The in vivo fate of lipid-based nanoparticles (LBNs) is essentially determined by
      the properties of their lipid compositions. LBNs are rapidly degraded via
      lipolysis wherever lipases are abundant, especially in the gastrointestinal
      tract. LBNs that survive lipolysis can be translocated through the circulation to
      reach terminal organs or tissues. Lipid composition, particle size, and surface
      decoration, as well as the formation of protein corona, are the main factors
      influencing the in vivo fate of LBNs. As we discuss here, elucidation of the in
      vivo fate of LBNs helps weigh the balance between lipolysis and biorecognition,
      and is emerging as a new field of research.

PMID- 27713036
TI  - Insulin resistance and Parkinson's disease: A new target for disease
      modification?
AB  - There is growing evidence that patients with Type 2 diabetes have an increased
      risk of developing Parkinson's disease and share similar dysregulated pathways
      suggesting common underlying pathological mechanisms. Historically insulin was
      thought solely to be a peripherally acting hormone responsible for glucose
      homeostasis and energy metabolism. However accumulating evidence indicates
      insulin can cross the blood-brain-barrier and influence a multitude of processes
      in the brain including regulating neuronal survival and growth, dopaminergic
      transmission, maintenance of synapses and pathways involved in cognition. In
      conjunction, there is growing evidence that a process analogous to peripheral
      insulin resistance occurs in the brains of Parkinson's disease patients, even in
      those without diabetes. This raises the possibility that defective insulin
      signalling pathways may contribute to the development of the pathological
      features of Parkinson's disease, and thereby suggests that the insulin signalling
      pathway may potentially be a novel target for disease modification. Given these
      growing links between PD and Type 2 diabetes it is perhaps not unsurprising that
      drugs used the treatment of T2DM are amongst the most promising treatments
      currently being prioritised for repositioning as possible novel treatments for PD
      and several clinical trials are under way. In this review, we will examine the
      underlying cellular links between insulin resistance and the pathogenesis of PD
      and then we will assess current and future pharmacological strategies being
      developed to restore neuronal insulin signalling as a potential strategy for
      slowing neurodegeneration in Parkinson's disease.

PMID- 27713037
TI  - Mitochondrial Amino Acid Metabolism Provides Vulnerabilities in Mutant KRAS
      Driven Cancers.

PMID- 27713039
TI  - Thoracic osteomyelitis: an unusual adverse event of esophageal stenting.

PMID- 27713038
TI  - Validation of Recently Proposed Colorectal Cancer Susceptibility Gene Variants in
      an Analysis of Families and Patients-a Systematic Review.
AB  - High-throughput sequencing analysis has accelerated searches for genes associated
      with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM,
      FAN1, TP53, BUB1, BUB3, LRP6, and PTPN12 have been recently proposed to increase
      CRC risk. We attempted to validate the association between variants in these
      genes and development of CRC in a systematic review of 11 publications, using
      sequence data from 863 familial CRC cases and 1604 individuals without CRC
      (controls). All cases were diagnosed at an age of 55 years or younger and did not
      carry mutations in an established CRC predisposition gene. We found sufficient
      evidence for NTHL1 to be considered a CRC predisposition gene-members of 3
      unrelated Dutch families were homozygous for inactivating p.Gln90Ter mutations; a
      Canadian woman with polyposis, CRC, and multiple tumors was reported to be
      heterozygous for the inactivating NTHL1 p.Gln90Ter/c.709+1G>A mutations; and a
      man with polyposis was reported to carry p.Gln90Ter/p.Gln287Ter; whereas no
      inactivating homozygous or compound heterozygous mutations were detected in
      controls. Variants that disrupted RPS20 were detected in a Finnish family with
      early-onset CRC (p.Val50SerfsTer23), a 39-year old individual with metachronous
      CRC (p.Leu61GlufsTer11 mutation), and a 41-year-old individual with CRC (missense
      p.Val54Leu), but not in controls. We therefore found published evidence to
      support the association between variants in NTHL1 and RPS20 with CRC, but not of
      other recently reported CRC susceptibility variants. We urge the research
      community to adopt rigorous statistical and biological approaches coupled with
      independent replication before making claims of pathogenicity.

PMID- 27713041
TI  - Reply.

PMID- 27713040
TI  - Tetrahydrocurcumin in combination with deferiprone attenuates hypertension,
      vascular dysfunction, baroreflex dysfunction, and oxidative stress in iron
      overloaded mice.
AB  - Excessive iron can generate reactive oxygen species (ROS), leading to oxidative
      stress that is closely associated with cardiovascular dysfunction. Iron overload
      was induced in male ICR mice by injection of iron sucrose (10mg/kg/day) for eight
      weeks. Iron overload was evidenced by increased serum iron indices. The mice
      developed increased blood pressure, impaired vascular function and blunted
      response of the autonomic nervous system. These effects were accompanied by
      increased malondialdehyde levels in various tissues, increased nitric oxide
      metabolites in plasma and urine, and decreased blood glutathione.
      Tetrahydrocurcumin (THU, 50mg/kg/day), deferiprone (or L1, 50mg/kg/day) or both
      was orally administered throughout the period of iron sucrose injection. The
      treatments significantly alleviated the deleterious cardiovascular effects of
      iron overload, and were associated with modulation of nitric oxide levels. An
      imbalance between endothelial nitric oxide synthase (eNOS) and inducible NOS
      (iNOS) expression in response to iron overload was normalized by THU, L1 or the
      combination treatment. Moreover, the treatment decreased the upregulated
      expression levels of gp91phox, p47phox and HO-1. The combination of THU and L1
      exerted a greater effect than THU or L1 monotherapy. These results suggest
      beneficial effects of THU and L1 on iron-induced oxidative stress, hypertension,
      and vascular dysfunction.

PMID- 27713042
TI  - An Uncommon Cause of Gas Gangrene.

PMID- 27713043
TI  - A Rare Cause of Massive Upper Gastrointestinal Bleeding.

PMID- 27713045
TI  - Uncertain Benefits of Simvastatin in the Treatment of Patients With Variceal
      Hemorrhage.

PMID- 27713044
TI  - Altered Pharmacokinetics of Statins Explain Increased Risk of Rhabdomyolysis in
      Advanced Cirrhosis.

PMID- 27713046
TI  - The Formation of a Yin-Yang Gallbladder: A Case Report and Potential Clinical
      Implication.

PMID- 27713047
TI  - An Unusual Cause of Recurrent Severe Abdominal Colic.

PMID- 27713048
TI  - An Unusual Cause of Rectal Invasion.

PMID- 27713050
TI  - The Golden Compass to the Depths.

PMID- 27713051
TI  - Reply.

PMID- 27713052
TI  - Accuracy of virtually 3D planned resection templates in mandibular
      reconstruction.
AB  - OBJECTIVE: Since reconstruction of composite defects in the head and neck region
      is a challenging and demanding problem for head and neck surgeons, surgical aids
      have been sought for decades. The purpose of this study was to evaluate the
      accuracy of prefabricated surgical resection templates used in mandibular
      segmental resections in comparison to the virtual surgical plan. MATERIALS AND
      METHODS: A prospective study was performed in 11 consecutive patients, with a
      primary T4 oral squamous cell carcinoma or osteoradionecrosis of the mandible.
      Preoperatively, a CBCT scan was acquired to delineate the size and extension of
      tumor invasion; a virtual patient-specific resection template was designed based
      on this information. Intraoperatively, the resection template was positioned on
      the mandible and secured using four fixation screws. Postoperatively, a CBCT scan
      was acquired. This scan was superimposed on the preoperative scan. Positioning of
      the resection template and inclination of the resection planes were evaluated on
      the virtual head model. In order to test the interobserver reliability of these
      new measurement methods, two different observers executed all measurements.
      RESULTS: The mean shift of the proximal resection templates was 3.76 mm (standard
      deviation [SD] 3.10 mm). For the distal resection templates, the mean shift was
      3.06 mm (SD 1.57 mm) with no significant interobserver difference (ICC = 0.99).
      An absolute mean deviation of 8.5 degrees  (SD 5.3 degrees ) was found for the
      proximal resection angle and 10.4 degrees  (SD 5.0 degrees ) for the distal
      resection angle. Again, no significant interobserver differences were found (ICC
      = 0.98). CONCLUSION: The resection templates used in this study proved reasonably
      accurate. Although the concept of virtual surgical planning aids significantly in
      mandibular reconstruction with microvascular free flaps, further improvement of
      resection accuracy is necessary for further improvement of reconstruction
      accuracy.

PMID- 27713053
TI  - Development of a virtual reality training system for endoscope-assisted
      submandibular gland removal.
AB  - PURPOSE: Endoscope-assisted surgery has widely been adopted as a basic surgical
      procedure, with various training systems using virtual reality developed for this
      procedure. In the present study, a basic training system comprising virtual
      reality for the removal of submandibular glands under endoscope assistance was
      developed. The efficacy of the training system was verified in novice oral
      surgeons. MATERIAL AND METHODS: A virtual reality training system was developed
      using existing haptic devices. Virtual reality models were constructed from
      computed tomography data to ensure anatomical accuracy. Novice oral surgeons were
      trained using the developed virtual reality training system. RESULTS: The
      developed virtual reality training system included models of the submandibular
      gland and surrounding connective tissues and blood vessels entering the
      submandibular gland. Cutting or abrasion of the connective tissue and
      manipulations, such as elevation of blood vessels, were reproduced by the virtual
      reality system. A training program using the developed system was devised. Novice
      oral surgeons were trained in accordance with the devised training program.
      CONCLUSIONS: Our virtual reality training system for endoscope-assisted removal
      of the submandibular gland is effective in the training of novice oral surgeons
      in endoscope-assisted surgery.

PMID- 27713054
TI  - Improving the accuracy of mandibular reconstruction with vascularized iliac crest
      flap: Role of computer-assisted techniques.
AB  - While vascularized iliac crest flap is widely used for mandibular reconstruction,
      it is often challenging to predict the clinical outcome in a conventional
      operation based solely on the surgeon's experience. Herein, we aimed to improve
      this procedure by using computer-assisted techniques. We retrospectively reviewed
      records of 45 patients with mandibular tumor who underwent mandibulectomy and
      reconstruction with vascularized iliac crest flap from January 2008 to June 2015.
      Computer-assisted techniques including virtual plan, stereomodel, pre-bending
      individual reconstruction plate, and surgical navigation were used in 15
      patients. The other 30 patients underwent conventional surgery based on the
      surgeon's experience. Condyle position and reconstructed mandible contour were
      evaluated based on post-operative computed tomography. Complications were also
      evaluated during the follow-up. Flap success rate of the patients was 95.6%
      (43/45). Those in the computer-assisted group presented with better outcomes of
      the mandibular contour (p = 0.001) and condyle position (p = 0.026). Further,
      they also experienced beneficial dental restoration (p = 0.011) and postoperative
      appearance (p = 0.028). The difference between postoperative effect and virtual
      plan was within the acceptable error margin. There is no significant difference
      in the incidence of post-operative complications. Thus, computer-assisted
      techniques can improve the clinical outcomes of mandibular reconstruction with
      vascularized iliac crest flap.

PMID- 27713055
TI  - Evolutionary history and spatiotemporal dynamics of DENV-1 genotype V in the
      Americas.
AB  - The genotype V has been the most prevalent dengue virus type 1 (DENV-1) clade
      circulating in the Americas over the last 40years. In this study, we investigate
      the spatiotemporal pattern of emergence and dissemination of DENV-1 lineages in
      the continent. We applied phylogenetic and phylogeographic approaches to a
      comprehensive data set of 836 DENV-1 E gene sequences of the genotype V isolated
      from 46 different countries around the world over a period of 50years (1962 to
      2014). Our study reveals that genetic diversity of DENV-1 genotype V in the
      Americas resulted from two independent introductions of this genotype from India.
      The first genotype V strain was most probably introduced into the Lesser Antilles
      at around the early 1970s and this Caribbean region becomes the source population
      of several DENV-1 lineages that spread in the Americas during the 1970s and
      1980s. Most of those lineages appear to become extinct during the 1990s, except
      one that persisted in Venezuela and later spread to other American countries,
      dominating the DENV-1 epidemics in the region from the early 2000s onwards. The
      second genotype V strain of Indian origin was also most probably introduced into
      the Lesser Antilles at around the early 1980s. This lineage remained almost
      undetected for nearly 15years, until it was introduced in Northern Brazil around
      the middle 1990s and later spread to other country regions. These results
      demonstrate that different geographic regions have played a role in maintaining
      and spreading the DENV-1 genotype V in the Americas over time. DENV-1 genotype V
      lineages have originated, spread and died out in the Americas with very different
      dynamics and the phenomenon of lineage replacement across successive DENV-1
      epidemic outbreaks was a common characteristic in most American countries.

PMID- 27713056
TI  - Cross-Disciplinary Analysis of Lymph Node Classification in Lung Cancer on CT
      Scanning.
AB  - BACKGROUND: Accurate and consistent regional lymph node classification is an
      important element in the staging and multidisciplinary management of lung cancer.
      Regional lymph node definition sets-lymph node maps-have been created to
      standardize regional lymph node classification. In 2009, the International
      Association for the Study of Lung Cancer (IASLC) introduced a lymph node map to
      supersede all preexisting lymph node maps. Our aim was to study if and how lung
      cancer specialists apply the IASLC lymph node map when classifying thoracic lymph
      nodes encountered on CT scans during lung cancer staging. METHODS: From April
      2013 through July 2013, invitations were distributed to all members of the
      Fleischner Society, Society of Thoracic Radiology, General Thoracic Surgical
      Club, and the American Association of Bronchology and Interventional Pulmonology
      to participate in an anonymous online image-based and text-based 20-question
      survey regarding lymph node classification for lung cancer staging on CT imaging.
      RESULTS: Three hundred thirty-seven people responded (approximately 25%
      participation). Respondents consisted of self-reported thoracic radiologists (n =
      158), thoracic surgeons (n = 102), and pulmonologists who perform endobronchial
      ultrasonography (n = 77). Half of the respondents (50%; 95% CI, 44%-55%) reported
      using the IASLC lymph node map in daily practice, with no significant differences
      between subspecialties. A disparity was observed between the IASLC definition
      sets and their interpretation and application on CT scans, in particular for
      lymph nodes near the thoracic inlet, anterior to the trachea, anterior to the
      tracheal bifurcation, near the ligamentum arteriosum, between the bronchus
      intermedius and esophagus, in the internal mammary space, and adjacent to the
      heart. CONCLUSIONS: Use of older lymph node maps and inconsistencies in
      interpretation and application of definitions in the IASLC lymph node map may
      potentially lead to misclassification of stage and suboptimal management of lung
      cancer in some patients.

PMID- 27713057
TI  - Signalling pathways in trophic skeletal development and morphogenesis: Insights
      from studies on teleost fish.
AB  - During the development of the vertebrate feeding apparatus, a variety of
      complicated cellular and molecular processes participate in the formation and
      integration of individual skeletal elements. The molecular mechanisms regulating
      the formation of skeletal primordia and their development into specific
      morphological structures are tightly controlled by a set of interconnected
      signalling pathways. Some of these pathways, such as Bmp, Hedgehog, Notch and
      Wnt, are long known for their pivotal roles in craniofacial skeletogenesis.
      Studies addressing the functional details of their components and downstream
      targets, the mechanisms of their interactions with other signals as well as their
      potential roles in adaptive morphological divergence, are currently attracting
      considerable attention. An increasing number of signalling pathways that had
      previously been described in different biological contexts have been shown to be
      important in the regulation of jaw skeletal development and morphogenesis. In
      this review, I provide an overview of signalling pathways involved in trophic
      skeletogenesis emphasizing studies of the most species-rich group of vertebrates,
      the teleost fish, which through their evolutionary history have undergone
      repeated episodes of spectacular trophic diversification.

PMID- 27713058
TI  - Organogenesis of adult lung in a dish: Differentiation, disease and therapy.
AB  - The remarkable regenerative capacity of the lung suggests that stem cells could
      be of therapeutic importance in diverse lung diseases; however, the successful
      exploitation of lung stem cell biology has long been hampered by our inability to
      maintain and expand adult lung stem cells while retaining their multi-lineage
      potential in vitro. Recently, advances in our understanding of stem cell niches
      and the role of key signalling modulators in controlling stem cell maintenance
      and differentiation have fuelled the development of new in vitro three
      dimensional (3D) culture technologies that sustain the stem cell-driven formation
      of near-physiological, self-organizing structures called organoids. Here we
      review basic approaches to organoid model systems and highlight recent
      achievements in the generation of organoids from adult stem and progenitor cells
      of both the murine and human lungs. We evaluate current applications in studying
      cellular changes in proliferation, differentiation, plasticity, and cell
      polarity, and cellular and molecular crosstalk of epithelial cells with stroma.
      Advantages and limitations of organoids for clinical use are also discussed.

PMID- 27713060
TI  - Affinity purification of native glycodelin from amniotic fluid for biological
      investigations and development of a glycodelin ELISA for clinical studies.
AB  - INTRODUCTION: Glycodelin is a glycoprotein with different oligosaccharides that
      are responsible for its diverse biological functions in contraception and
      immunosuppression. Therefore, it is necessary to have access to adequate amounts
      of glycodelin with retained carbohydrate structure for functional studies because
      the carbohydrate part can be lacking or be insufficient in recombinant glycodelin
      from prokaryotic and eukaryotic cell systems. METHODS AND RESULTS: Native
      glycodelin was purified from amniotic fluid by a series of affinity
      chromatography steps and had many glycosylated forms verified by mass
      spectrometry. About 7.5 mg glycodelin was obtained from 1.5 L amniotic fluid. No
      high molecular mass forms of glycodelin were found in amniotic fluid. Aliquots of
      the purified glycodelin were used as an immunogen in rabbits for antibody
      production against glycodelin and a calibrator in a highly sensitive glycodelin
      enzyme-linked immunosorbent assay (ELISA) with a detection limit of about 1
      MUg/L. CONCLUSIONS: Native glycodelin was purified from amniotic fluid and used
      as an immunogen for raising a rabbit antibody against glycodelin and a calibrator
      in a highly sensitive glycodelin ELISA. We found no high molecular mass forms of
      glycodelin in amniotic fluid. Aliquots of the purified glycodelin were set aside
      for functional studies which are in progress.

PMID- 27713059
TI  - Bmp4-Msx1 signaling and Osr2 control tooth organogenesis through antagonistic
      regulation of secreted Wnt antagonists.
AB  - Mutations in MSX1 cause craniofacial developmental defects, including tooth
      agenesis, in humans and mice. Previous studies suggest that Msx1 activates Bmp4
      expression in the developing tooth mesenchyme to drive early tooth organogenesis.
      Whereas Msx1-/- mice exhibit developmental arrest of all tooth germs at the bud
      stage, mice with neural crest-specific inactivation of Bmp4 (Bmp4ncko/ncko),
      which lack Bmp4 expression in the developing tooth mesenchyme, showed
      developmental arrest of only mandibular molars. We recently demonstrated that
      deletion of Osr2, which encodes a zinc finger transcription factor expressed in a
      lingual-to-buccal gradient in the developing tooth bud mesenchyme, rescued molar
      tooth morphogenesis in both Msx1-/- and Bmp4ncko/ncko mice. In this study,
      through RNA-seq analyses of the developing tooth mesenchyme in mutant and
      wildtype embryos, we found that Msx1 and Osr2 have opposite effects on expression
      of several secreted Wnt antagonists in the tooth bud mesenchyme. Remarkably, both
      Dkk2 and Sfrp2 exhibit Osr2-dependent preferential expression on the lingual side
      of the tooth bud mesenchyme and expression of both genes was up-regulated and
      expanded into the tooth bud mesenchyme in Msx1-/- and Bmp4ncko/ncko mutant
      embryos. We show that pharmacological activation of canonical Wnt signaling by
      either lithium chloride (LiCl) treatment or by inhibition of DKKs in utero was
      sufficient to rescue mandibular molar tooth morphogenesis in Bmp4ncko/ncko mice.
      Furthermore, whereas inhibition of DKKs or inactivation of Sfrp2 alone was
      insufficient to rescue tooth morphogenesis in Msx1-/- mice, pharmacological
      inhibition of DKKs in combination with genetic inactivation of Sfrp2 and Sfrp3
      rescued maxillary molar morphogenesis in Msx1-/- mice. Together, these data
      reveal a novel mechanism that the Bmp4-Msx1 pathway and Osr2 control tooth
      organogenesis through antagonistic regulation of expression of secreted Wnt
      antagonists.

PMID- 27713061
TI  - The Total Calvarial Transsutural Distraction Osteogenesis for 26 Children with
      Slit Ventricle, Craniosynostosis, or Microcephaly After Shunt Operation.
AB  - OBJECTIVE: Among shunt complications, the postshunt slit ventricle (PSSV) and the
      postshunt craniosynostosis (PSCS) may be managed by shunt valve upgrade and/or
      cranial expansion surgery. Here, we analyzed 26 children with PSSV, PSCS, or
      microcephaly who received simple generalized cranial expansion (ie, total
      calvarial transsutural distraction osteogenesis [TC-TSuDO]). METHODS: Among 254
      children with shunt surgery, 26 children received TC-TSuDO. These 26 children
      included 14 with PSSV, 4 with PSCS, and 8 with both PSSV and PSCS. The mean age
      of patients who underwent shunt procedures was 8.2 +/- 10.6 months, and the mean
      time interval from shunt surgery to TC-TSuDO was 26.8 +/- 29.5 months. The mean
      age of children at the time of TC-TSuDO was 33.3 +/- 30.2 months. We analyzed
      head circumferences, lumbar puncture pressures, development status, operative
      factors, and postoperative complications. RESULTS: The mean preoperative head
      circumference was -2.1 +/- 1.9, which increased to -1.4 +/- 2.1 (P < 0.001)
      postsurgically. The mean preoperative lumbar puncture pressure was 26.2 +/- 10.7
      cm H2O which decreased to 11.9 +/- 3.5 cm H2O (P < 0.001) after surgery. The mean
      operation time was 138 +/- 66 minutes. The mean intensive care unit stay was 0.27
      +/- 0.53 days. There were no mortalities but 2 patients suffered from distractor
      malfunction and 1 patient showed wound discharge. CONCLUSIONS: We suggest that
      postshunt complications such as PSSV or PSCS, especially those that are
      accompanied by increased intracranial pressure or postshunt microcephaly, may be
      managed for patients with TC-TSuDO, which has been shown to be safe, simple, and
      effective.

PMID- 27713062
TI  - Intradural Carcinoid Tumor Found in a Patient with No History of Cancer.
AB  - BACKGROUND: Carcinoid tumors are rare neoplasms that often arise from the
      gastrointestinal or respiratory tracts. They often metastasize to bone tissue and
      pancreatic and hepatic sites. The central nervous system and most specifically
      the spinal cord are rarely involved. Primary carcinoid tumors of the central
      nervous system are even rarer. CASE DESCRIPTION: A 58-year-old man presented with
      progressive bilateral lower extremity weakness and a negative history of cancer.
      Imaging revealed an intradural mass at the L1 and L2 spinal levels. Surgical
      resection of the tumor via laminectomy was performed. The tumor was observed to
      have eroded through the dura and was compressing the spinal nerves.
      Histopathologically, the mass was observed to be of carcinoid origin. A
      subsequent octreoscan revealed no primary sites of carcinoid tumor.
      Postoperatively, the patient was followed for 1.5 years. The patient reported
      improvement in sensation to his lower extremities with no change in motor
      findings. CONCLUSIONS: Carcinoid tumors of the central nervous system are
      extremely rare, but they should remain in the differential diagnosis for patients
      experiencing extremity weakness and back or neck pain with an intradural mass and
      no primary source of the tumor identified or other manifestations of a primary
      tumor.

PMID- 27713063
TI  - Radiation-Induced Meningiomas: An Exhaustive Review of the Literature.
AB  - OBJECTIVE: Radiation-induced meningioma (RIM) is an uncommon late risk of cranial
      irradiation. We conducted an exhaustive review of individual patient data to
      characterize RIM. METHODS: Using a systematic search of the PubMed database, we
      performed a comprehensive literature review to characterize and investigate RIM.
      Student t tests were used to evaluate differences between variables. A Kaplan
      Meier analysis was used to assess survival. Statistical significance was assessed
      using a log-rank test. RESULTS: Our analysis included 251 cases of RIM. The
      average age at onset for the primary lesion was 13.0 +/- 13.5 years, and the
      average radiation dose delivered to this lesion was 38.8 +/- 16.8 Gy. Secondary
      meningiomas could be divided into grades I (140), II (55), and III (10) tumors.
      Thirty patients (11.9%) had multiple lesions, and 46 (18.3%) had recurrent
      meningiomas. The latency period between radiotherapy for primary lesions and the
      onset of meningiomas was 22.9 +/- 11.4 years. The latency period was shorter for
      patients with grade III meningioma and for those in the high-dose and
      intermediate-dose radiation groups who received systemic chemotherapy. Aggressive
      meningiomas and multiple meningiomas were more common in the high-dose and
      intermediate-dose groups than in the low-dose group. The 5-year and 10-year
      survival rates for all patients with meningioma were 77.7% and 66.1%,
      respectively. CONCLUSIONS: For patients treated with cranial radiotherapy, the
      risk of secondary meningioma warrants a longer follow-up period beyond the
      standard time frame typically designated for determining the risk of primary
      tumor relapse.

PMID- 27713064
TI  - Aggressive Pituitary Adenomas: The Dark Side of the Moon.
AB  - BACKGROUND: Although pituitary adenomas are considered benign lesions, a small
      group may show clinically aggressive behavior, sometimes independently from the
      classic markers of aggressiveness, including the Ki67 labeling index or p53
      expression. METHODS: We selected 7 patients harboring a pituitary tumor with
      clinical features of aggressiveness. Patients underwent a full preoperative and
      postoperative endocrinologic and neuroradiologic workup. Two were nonfunctioning,
      2 prolactin-secreting, 2 adrenocorticotrophic hormone-secreting, and 1 a growth
      hormone-secreting adenoma. RESULTS: The 7 patients underwent a total of 17
      surgical procedures. At the first surgical procedure, gross total removal was
      achieved in none of the patients, whereas subtotal removal (>90% of tumor
      removed) was achieved in 4/7 cases and partial removal (<90% of tumor removed) in
      3/7 cases. At first operation, 4/7 patients showed a Ki67 index <=3% and 2/7 >3%;
      this information was not available for 1 patient. Postoperatively, all patients
      underwent radiation therapy. Three patients received chemotherapy with
      temozolomide. Three patients underwent peptide receptor radionuclide therapy. To
      date, 1 patient has died of tumor progression, and 2 patients are in a poor
      general condition. The remaining 4 patients are in a fair/good condition, without
      any major complaints. The mean follow-up is 43.42 months. CONCLUSIONS: Aggressive
      pituitary adenomas represent a specific and still underestimated entity, often
      diagnosed late. Clinical and neuroradiologic rapid progression is often the only
      marker of aggressiveness. Surgical debulking remains the first therapeutic
      option. Multidisciplinary management is mandatory to offer these patients
      targeted therapeutic options.

PMID- 27713065
TI  - Using Intraoperative Ultrasonography for Spinal Cord Tumor Surgery.
AB  - BACKGROUND: Our aim was to evaluate the usefulness of modern intraoperative
      ultrasonography (iUS) in the resection of a wide variety of spinal intradural
      pathologic entities. METHODS: We evaluated patients with spinal cord disease
      treated between January 2006 and September 2015. Intraoperative standard B-mode
      images were acquired using a 3.5-MHz to 12-MHz ultrasonographic probes (linear
      and curvilinear) on various ultrasound machines. The benefits and disadvantages
      of iUS were assessed for each case. RESULTS: A total number of 158 intradural
      spinal lesions were operated on using iUS. Of these, 107 lesions (68%) were
      intradural extramedullary and 51 (32%) were intramedullary. All lesions were
      clearly visible using the ultrasound probe. The high-frequency linear probes (10
      12 MHz) provided a better image quality compared with lower-frequency probes.
      Color and power-angiography modes were helpful in assessing the vascularization
      of the tumors and location of the major vessels in the vascular lesions.
      DISCUSSION: We document how iUS was used to facilitate safe and efficient spinal
      tumor resection at each stage of the operation. iUS was beneficial in
      confirmation of tumor location and extension, planning myelotomy, and estimation
      of degree of resection of the intramedullary tumors. It was particularly helpful
      in guiding the approach in redo surgeries for recurrent spinal cord tumors.
      CONCLUSIONS: iUS has a fast learning curve and offers additional intraoperative
      information that can help improve surgical accuracy and therefore may reduce
      procedure-related morbidity.

PMID- 27713066
TI  - Impact of Age on Change in Self-Image 5 Years After Complex Spinal Fusion (>=5
      Levels).
AB  - BACKGROUND: Spinal deformities that require >=5 fusion levels are difficult and
      challenging for both the surgeon and patient. Corrections of moderate to severe
      deformities have been shown to improve patient-reported outcomes (PROs), and
      provide patients with a better quality of life. Self-image is an important PRO
      because it sheds insight into the patient's perception of health, as well as
      serving as a proxy of satisfaction for patients with spine deformity undergoing
      corrective surgery. However, with an aging population, the impact of age on long
      term change in self-image is unknown. The aim of this study is to determine the
      effects of age on self-image 5 years after undergoing an elective complex spinal
      fusion (>=5 levels). METHODS: This was a retrospective analysis of prospectively
      collected data of 55 adult patients (>=18 years old) undergoing >=5 levels of
      spinal fusion to the sacrum with iliac fixation from January 2002 to December
      2008. Patients were grouped by age: young (<60 years old) and older (>=60 years
      old). Patient demographics, comorbidities, preoperative variables (sagittal and
      Cobb angles) and postoperative complication rates were collected. All patients
      had prospectively collected outcome measures and a minimum of 5 years follow-up.
      PRO instrument SRS-22r (function, self-image, mental health, and pain) was
      completed before surgery then at follow-up (at least 5 years after surgery). The
      primary outcome investigated in this study was the change in self-image after
      surgery. RESULTS: Baseline characteristics and preoperative variables were
      similar in both cohorts. There were no significant differences in intraoperative
      variables, including the mean +/- standard deviation number of fusion levels
      between the cohorts (young, 11.2 +/-4.3 vs. older, 12.1 +/- 4.0; P = 0.42).
      Complication rates were similar between the cohorts, with no significant
      differences in the types of complications (young, 29.63% vs. older, 25.0%; P =
      0.77). There were no significant differences in preoperative and follow-up PROs
      between the cohorts. The mean +/- standard deviation preoperative and follow-up
      self-image scores were (young, 2.35+/-0.58 vs. older, 2.68 +/- 0.64; P = 0.51)
      and (young, 3.82 +/- 0.63 vs. older, 3.51 +/- 0.94), respectively. There were no
      significant differences in the change of function, mental health, or pain between
      the cohorts. However, the younger cohort experienced a significantly greater
      overall change in self-image than did the older cohort (young, 1.49 +/- 0.87 vs.
      older, 0.70+/-1.14; P = 0.01). CONCLUSIONS: Our study suggests that age
      significantly affects the perception of self-image after deformity correction
      surgery; with younger patients reporting a greater change from baseline in self
      image after surgery. Further studies are necessary to corroborate our observed
      findings.

PMID- 27713067
TI  - Clinical Experience with Intraoperative Ultrasonographic Image in Microsurgical
      Resection of Cerebral Arteriovenous Malformations.
AB  - BACKGROUND: Intraoperative ultrasonography is widely used in neurosurgery for the
      management of intracerebral hematoma and brain tumor. However, the clinical value
      of this method in the surgery of cerebral arteriovenous malformations (AVMs) has
      not been reported. In this study, the application of intraoperative
      ultrasonography for AVM surgery was evaluated prospectively. METHODS: This
      prospective clinical study comprised 41 patients who underwent microsurgical
      resection of cerebral AVMs at our institute. After routine craniotomy,
      ultrasonographic imaging with color Doppler ultrasonography and real-time
      contrast-enhanced ultrasonographic angiography if necessary were applied as
      navigated images on the monitor during the operation. RESULTS: Ultrasonographic
      imaging made it easier to understand the vascular architecture during the
      operation. Color Doppler flow imaging clearly delineated the shape and margin of
      the AVMs. Intraoperative real-time contrast-enhanced ultrasonographic angiography
      enabled the surgeons to categorically identify AVM feeders both on the surface
      and deep in the tissue. CONCLUSIONS: Microneurosurgery with intraoperative
      ultrasonographic image guidance was a safe, effective, and reliable method for
      identifying the afferent and efferent vessels and for confirming the complete
      resection of AVMs. These benefits of image-guided microsurgery were mostly
      apparent for deep-seated AVMs that were not visible on the surface of the brain.

PMID- 27713068
TI  - Cloning and expression study of a Toll-like receptor 2 (tlr2) gene from turbot,
      Scophthalmus maximus.
AB  - Toll-like receptor 2 (TLR2) in mammals is a member of the ancient Toll-like
      family of receptors that predominantly recognizes conserved components of Gram
      positive bacteria. In the present study, a tlr2 gene and its 5'-flanking sequence
      were cloned from turbot, Scophthalmus maximus, its responsive expressions to
      various immunostimulants were subsequently studied in vivo. The turbot (sm)tlr2
      gene spans over 9.0 kb with a structure of 12 exon-11 intron and encodes 816
      amino acids. The deduced protein shows the highest sequence identity (76.1%) to
      Japanese flounder Tlr2 and possesses a signal peptide sequence, a leucine-rich
      repeat (LRR) domain composed of 19 LRR motifs, a transmembrane region and a
      Toll/interleukin-1 receptor (TIR) domain. Phylogenetic analysis grouped it with
      other neoteleostei Tlr2as. A number of transcription factor binding sites known
      to be important for the basal transcriptional activity of TLR3 and response of
      TLR2 to lipopolysaccharide (LPS) signalling in mammals were predicted in the 5'
      flanking sequence of smtlr2. Quantitative real-time PCR (qPCR) analysis
      demonstrated the constitutive expression of smtlr2 mRNA in all twelve examined
      tissues with higher levels in the lymphomyeloid-rich tissues and liver. Further,
      smtlr2 expression was up-regulated following stimulation with LPS, peptidoglycan
      (PGN) or polyinosinic: polycytidylic acid [poly(I:C)] in the gills, head kidney,
      spleen and muscle. Finally, for all three immunostimulants, a two-wave induced
      smtlr2 expression was observed in the head kidney and spleen in a 7-day time
      course and the strongest inducibility in the head kidney. These findings suggest
      a possible role of Smtlr2 in the immune responses to the infections of a broad
      range of pathogens that include Gram-positive and Gram-negative bacteria and RNA
      virus.

PMID- 27713069
TI  - A Neurophysiological examination of quality of learning in a feedback-based
      learning task.
AB  - The efficiency with which one processes external feedback contributes to the
      speed and quality of one's learning. Previous findings that the feedback related
      negativity (FRN) event related potential (ERP) is modulated by learning outcomes
      suggested that this ERP reflects the extent to which feedback is used by the
      learner to improve performance. To further test this suggestion, we measured
      whether the FRN and the fronto-central positivity (FCP) that follows it are
      modulated by learning slopes, and as a function of individual differences in
      learning outcomes. Participants were tasked with learning names (non-words) of 42
      novel objects in a two-choice feedback-based visual learning task. The items were
      divided into three sets of 14 items, each presented in five learning blocks and a
      sixth test block. Individual learning slopes based on performance on the task, as
      well as FRN and FCP slopes based on positive and negative feedback related
      activation in each block were created for 53 participants. Our data pointed to an
      interaction between slopes of the FRN elicited by negative feedback and learning
      slopes, such that a sharper decrease in the amplitude of the FRN to negative
      feedback was associated with sharper learning slopes. We further examined the
      predictive power of the FRN and FCP elicited in the training blocks on the
      learning outcomes as measured by performance on the test blocks. We found that
      small FRN to negative feedback, large FRN to positive feedback, and large FCP to
      negative feedback in the first training block predicted better learning outcomes.
      These results add to the growing evidence that the processes giving rise to the
      FRN and FCP are sensitive to individual differences in the extent to which
      feedback is used for learning.

PMID- 27713070
TI  - Renal Parenchyma to Hydronephrosis Area Ratio (PHAR) as a Predictor of Future
      Surgical Intervention for Infants With High-grade Prenatal Hydronephrosis.
AB  - OBJECTIVE: To explore the potential value of an objective assessment, renal
      parenchyma to hydronephrosis area ratio (PHAR), as an early predictor of surgery.
      METHODS: Initial sagittal renal ultrasound (US) images of patients prospectively
      entered into a prenatal hydronephrosis database from January 2008 to January 2016
      with baseline Society for Fetal Urology (SFU) grades III and IV prenatal
      hydronephrosis, without vesicoureteral reflux, were evaluated using the National
      Institutes of Health-sponsored image processing software. PHAR, anteroposterior
      diameter, SFU grade, and urinary tract dilation risk categories were contrasted
      with nuclear scan data (differential renal function and drainage time [t1/2]) and
      analyzed for predictive value in determining the decision to proceed with surgery
      by drawing receiver operating characteristic curves. RESULTS: Out of 196 infants
      (162 male; 138 left sided hydronephrosis), 58 (30%) underwent surgery to address
      obstruction. Surgical patients compared with those managed conservatively had
      longer t1/2 (60 vs 18 min; P < .01) and lower differential renal function (46 vs
      50%; P = .01). Of the initial US parameters, PHAR (area under the curve = 0.816;
      P < .001) had a better predictive performance than anteroposterior diameter, SFU
      grade, or urinary tract dilation classification. PHAR values correlated with
      subsequent parameters obtained on nuclear scan. CONCLUSION: PHAR is a promising
      parameter that can be estimated on presentation US to help predict future need
      for surgery in newborns with high-grade hydronephrosis.

PMID- 27713071
TI  - Evaluation of the orthopaedics and traumatology resident education in Turkey: A
      descriptive study.
AB  - OBJECTIVE: The objective of this study is to describe the current situation
      regarding the training, working conditions, future plans, fields of interest and
      satisfaction of orthopaedics and traumatology residents in Turkey. METHODS: A
      descriptive survey questionnaire consisting of 24 questions was designed to
      identify the problems and solution suggestions concerning training of orthopaedic
      residents. All orthopaedics and traumatology residents who took the 2013 Progress
      Testing for Speciality in Medicine (UEGS) held by Turkish Orthopaedics and
      Traumatology Education Council (TOTEK) were surveyed in the class at the end
      thereof as well as the young orthopaedic surgeons who were reached through the
      email groups of Turkish Society of Orthopaedics and Traumatology - Residents and
      Young Attendings Council (TOTBID-AGUH). RESULTS: A total of 725 residents and 132
      young attendings were surveyed. The most outstanding answers are as follows:
      62,7% of the respondents replied to the question "Is there a training program/Is
      it being applied" as "yes/yes". It was found out that 94,3% of the respondents
      wanted to be involved in a rotation abroad. The "patient care" was the most
      common answer, with a ratio of 36,9%, to the question "What's the priority of the
      department you are studying in?". Regarding work conditions, "many emergency on
      calls" was found to be the most important parameter affecting life conditions (p
      < 0.05). CONCLUSION: Aiming to identify the challenges that orthopaedics and
      traumatology residents in Turkey face as regards their training, this survey
      stands as a pioneering study with a high participation rate. Analysis of survey
      data highlights the importance of several key factors such as the development of
      training programs and increasing the time spent with academicians as well as
      spreading and promotion of log book application.

PMID- 27713072
TI  - GRADE Evidence to Decision (EtD) frameworks for adoption, adaptation, and de novo
      development of trustworthy recommendations: GRADE-ADOLOPMENT.
AB  - BACKGROUND: Guideline developers can: (1) adopt existing recommendations from
      others; (2) adapt existing recommendations to their own context; or (3) create
      recommendations de novo. Monetary and nonmonetary resources, credibility,
      maximization of uptake, as well as logical arguments should guide the choice of
      the approach and processes. OBJECTIVES: To describe a potentially efficient model
      for guideline production based on adoption, adaptation, and/or de novo
      development of recommendations utilizing the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD)
      frameworks. STUDY DESIGN AND SETTING: We applied the model in a new national
      guideline program producing 22 practice guidelines. We searched for relevant
      evidence that informs the direction and strength of a recommendation. We then
      produced GRADE EtDs for guideline panels to develop recommendations. RESULTS: We
      produced a total of 80 EtD frameworks in approximately 4 months and 146 EtDs in
      approximately 6 months in two waves. Use of the EtD frameworks allowed panel
      members understand judgments of others about the criteria that bear on guideline
      recommendations and then make their own judgments about those criteria in a
      systematic approach. CONCLUSION: The "GRADE-ADOLOPMENT" approach to guideline
      production combines adoption, adaptation, and, as needed, de novo development of
      recommendations. If developers of guidelines follow EtD criteria more widely and
      make their work publically available, this approach should prove even more
      useful.

PMID- 27713073
TI  - A chronological review of experimental infection studies of the role of wild
      animals and livestock in the maintenance and transmission of Crimean-Congo
      hemorrhagic fever virus.
AB  - This article provides a definitive review of experimental studies of the role of
      wild animals and livestock in the maintenance and transmission of Crimean-Congo
      hemorrhagic fever virus (CCHFV), the etiologic agent of Crimean-Congo hemorrhagic
      fever (CCHF), beginning with the first recognized outbreak of the human disease
      in Crimea in 1944. Published reports by researchers in the former Soviet Union,
      Bulgaria, South Africa, and other countries where CCHF has been observed show
      that CCHFV is maintained in nature in a tick-vertebrate-tick enzootic cycle.
      Human disease most commonly results from the bite of an infected tick, but may
      also follow crushing of infected ticks or exposure to the blood and tissues of
      infected animals during slaughter. Wild and domestic animals are susceptible to
      infection with CCHFV, but do not develop clinical illness. Vertebrates are
      important in CCHF epidemiology, as they provide blood meals to support tick
      populations, transport ticks across wide geographic areas, and transmit CCHFV to
      ticks and humans during the period of viremia. Many aspects of vertebrate
      involvement in the maintenance and spread of CCHFV are still poorly understood.
      Experimental investigations in wild animals and livestock provide important data
      to aid our understanding of CCHFV ecology. This article is the second in a series
      of reviews of more than 70 years of research on CCHF, summarizing important
      findings, identifying gaps in knowledge, and suggesting directions for future
      research.

PMID- 27713076
TI  - Fear of Movement Is Not Associated With Objective and Subjective Physical
      Activity Levels in Chronic Nonspecific Low Back Pain.
AB  - OBJECTIVES: To assess the association of physical activity measures, derived with
      an accelerometer and a self-reported questionnaire, with fear of movement in
      patients with chronic nonspecific low back pain (LBP) and to investigate the
      association between disability and fear of movement in this population. DESIGN:
      Cross-sectional study. SETTING: Outpatient physical therapy university clinics.
      PARTICIPANTS: Patients (N=119) presenting with nonspecific LBP of >3 months'
      duration. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Physical activity
      levels measured objectively with an accelerometer (ie, counts per minute, time
      spent in moderate-to-vigorous and light physical activity per day, number of
      steps per day, and number of 10-minute bouts of moderate-to-vigorous physical
      activity per day) and subjectively with a self-reported questionnaire (Baecke
      Physical Activity Questionnaire); fear of movement (Tampa Scale of
      Kinesiophobia); pain (11-point numerical rating scale); disability (Roland Morris
      Disability Questionnaire); and depression (Beck Depression Inventory). The
      associations were examined with correlational, univariate, and multivariable
      linear regression analyses. RESULTS: None of the objective physical activity
      measures were associated with fear of movement. The apparent association of self
      reported physical activity levels with fear of movement (correlational analyses:
      r=-.18; P<.05; univariate regression analyses: beta=-.04; 95% confidence interval
      [CI], -.07 to -.01; P=.04) was not confirmed in multivariable analyses. Fear of
      movement was consistently associated with disability in both correlational
      (r=.42; P<.01) and multivariable (beta=.21; 95% CI, .11-.31; P<.001) analyses.
      CONCLUSIONS: Our data support one aspect of the fear-avoidance model-that higher
      fear of movement is associated with more disability-but not the aspect of the
      model linking fear of movement with inactivity.

PMID- 27713074
TI  - An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody with
      prophylactic and therapeutic activity in vivo.
AB  - Zoonotic A(H7N9) avian influenza viruses emerged in China in 2013 and continue to
      be a threat to human public health, having infected over 800 individuals with a
      mortality rate approaching 40%. Treatment options for people infected with
      A(H7N9) include the use of neuraminidase (NA) inhibitors. However, like other
      influenza viruses, A(H7N9) can become resistant to these drugs. The use of
      monoclonal antibodies is a rapidly developing strategy for controlling influenza
      virus infection. Here we generated a murine monoclonal antibody (3c10-3) directed
      against the NA of A(H7N9) and show that prophylactic systemic administration of
      3c10-3 fully protected mice from lethal challenge with wild-type A/Anhui/1/2013
      (H7N9). Further, post-infection treatment with a single systemic dose of 3c10-3
      at either 24, 48 or 72 h post A(H7N9) challenge resulted in both dose- and time
      dependent protection of up to 100% of mice, demonstrating therapeutic potential
      for 3c10-3. Epitope mapping revealed that 3c10-3 binds near the enzyme active
      site of NA, and functional characterization showed that 3c10-3 inhibits the
      enzyme activity of NA and restricts the cell-to-cell spread of the virus in
      cultured cells. Affinity analysis also revealed that 3c10-3 binds equally well to
      recombinant NA of wild-type A/Anhui/1/2013 and to a variant NA carrying a R289K
      mutation known to infer NAI resistance. These results suggest that 3c10-3 has the
      potential to be used as a therapeutic to treat A(H7N9) infections either as an
      alternative to, or in combination with, current NA antiviral inhibitors.

PMID- 27713077
TI  - Noninfectious complications in patients with pediatric-onset common variable
      immunodeficiency correlated with defects in somatic hypermutation but not in
      class-switch recombination.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous syndrome
      characterized by impaired immunoglobulin production and usually presents with a
      normal quantity of peripheral B cells. Most attempts aiming to classify these
      patients have mainly been focused on T- or B-cell phenotypes and their ability to
      produce protective antibodies, but it is still a major challenge to find a
      suitable classification that includes the clinical and immunologic heterogeneity
      of these patients. OBJECTIVE: In this study we evaluated the late stages of B
      cell differentiation in a heterogeneous population of patients with pediatric
      onset CVID to clinically correlate and assess their ability to perform somatic
      hypermutation (SHM), class-switch recombination (CSR), or both. METHODS: We
      performed a previously reported assay, the restriction enzyme hotspot mutation
      assay (IgkappaREHMA), to evaluate in vivo SHM status. We amplified switch regions
      from genomic DNA to investigate the quality of the double-strand break repairs in
      the class-switch recombination process in vivo. We also tested the ability to
      generate immunoglobulin germline and circle transcripts and to upregulate the
      activation-induced cytidine deaminase gene through in vitro T-dependent and T
      independent stimuli. RESULTS: Our results showed that patients could be
      classified into 2 groups according to their degree of SHM alteration. This
      stratification showed a significant association between patients of group A,
      severe alteration, and the presence of noninfectious complications. Additionally,
      60% of patients presented with increased microhomology use at switched regions.
      In vitro activation revealed that patients with CVID behaved heterogeneously in
      terms of responsiveness to T-dependent stimuli. CONCLUSIONS: The correlation
      between noninfectious complications and SHM could be an important tool for
      physicians to further characterize patients with CVID. This categorization would
      help to improve elucidation of the complex mechanisms involved in B-cell
      differentiation pathways.

PMID- 27713075
TI  - Quality and Equity in Wheelchairs Used by Veterans.
AB  - OBJECTIVES: To assess in Veterans with spinal cord injury (SCI) or amputated limb
      (AL) the following: (1) patient demographics, medical factors, cultural and
      psychosocial characteristic by race; (2) wheelchair quality by race; and (3) the
      independent associations of patient race and the other factors with wheelchair
      quality. DESIGN: Cross-sectional cohort study. SETTING: Three Department of
      Veterans Affairs (VA) medical centers affiliated with academic medical centers.
      PARTICIPANTS: Eligible participants were Veterans with SCI or ALs (N=516); 482 of
      them completed the interview. Analyses were restricted to white and African
      American participants. Because there was no variation in wheelchair quality among
      AL patients (n=42), they were excluded from all but descriptive analyses, leading
      to a final sample size of 421. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: Wheelchair quality as defined by the Medicare Healthcare Common
      Procedure Coding System. RESULTS: We found race differences in many of our
      variables, but not in quality for manual (odds ratio [OR]=.67; 95% confidence
      interval [CI], .33-1.36) or power (OR=.82; 95% CI, .51-1.34) wheelchairs. Several
      factors including age (OR=.96; 95% CI, .93-.99) and income (OR=3.78; 95% CI, 1.43
      9.97) were associated with wheelchair quality. There were no significant
      associations of cultural or psychosocial factors with wheelchair quality.
      CONCLUSIONS: Although there were no racial differences in wheelchair quality, we
      found a significant association of older age and lower income with poorer
      wheelchair quality among Veterans. Efforts are needed to raise awareness of such
      disparities among VA wheelchair providers and to take steps to eliminate these
      disparities in prescription practice across VA sites.

PMID- 27713079
TI  - Corrigendum to "The transport mechanism of the mitochondrial ADP/ATP carrier"
      [Biochim. Biophys. Acta 1863/10 (2016) 2379-2393].

PMID- 27713078
TI  - Cardiac ankyrin repeat protein attenuates cardiomyocyte apoptosis by upregulation
      of Bcl-2 expression.
AB  - Cardiac ankyrin repeat protein (CARP) is a nuclear transcriptional co-factor that
      has additional functions in the myoplasm as a component of the muscle sarcomere.
      Previous studies have demonstrated increased expression of CARP in cardiovascular
      diseases, however, its role in cardiomyocyte apoptosis is unclear and
      controversial. In the present study, we investigated possible roles of CARP in
      hypoxia/reoxygenation (H/R) -induced cardiomyocyte apoptosis and the underlying
      mechanisms. Neonatal mouse ventricular cardiomyocytes were isolated and infected
      with adenovirus encoding Flag-tagged CARP (Ad-CARP) and lentivirus encoding CARP
      targeted shRNA (sh-CARP), respectively. Cardiomyocyte apoptosis induced by
      exposure to H/R conditions was evaluated by TUNEL staining and western blot
      analysis of cleaved caspase-3. The results showed that H/R-induced apoptosis was
      significantly decreased in Ad-CARP cardiomyocytes and increased in sh-CARP
      cardiomyocytes, suggesting a protective anti-apoptosis role for CARP.
      Interestingly, over-expressed CARP was mainly distributed in the nucleus,
      consistent with its role in regulating transcriptional activity. qPCR analysis
      showed that Bcl-2 transcripts were significantly increased in Ad-CARP
      cardiomyocytes. ChIP and co-IP assays confirmed the binding of CARP to the Bcl-2
      promoter through interaction with transcription factor GATA4. Collectively, our
      results suggest that CARP can protect against H/R induced cardiomyocyte
      apoptosis, possibly through increasing anti-apoptosis Bcl-2 gene expression.

PMID- 27713080
TI  - Synthetic and editing reactions of aminoacyl-tRNA synthetases using cognate and
      non-cognate amino acid substrates.
AB  - The covalent coupling of cognate amino acid-tRNA pairs by corresponding aminoacyl
      tRNA synthetases (aaRS) defines the genetic code and provides aminoacylated tRNAs
      for ribosomal protein synthesis. Besides the cognate substrate, some non-cognate
      amino acids may also compete for tRNA aminoacylation. However, their
      participation in protein synthesis is generally prevented by an aaRS proofreading
      activity located in the synthetic site and in a separate editing domain. These
      mechanisms, coupled with the ability of certain aaRSs to discriminate well
      against non-cognate amino acids in the synthetic reaction alone, define the
      accuracy of the aminoacylation reaction. aaRS quality control may also act as a
      gatekeeper for the standard genetic code and prevents infiltration by natural
      amino acids that are not normally coded for protein biosynthesis. This latter
      finding has reinforced interest in understanding the principles that govern
      discrimination against a range of potential non-cognate amino acids. This paper
      presents an overview of the kinetic assays that have been established for
      monitoring synthetic and editing reactions with cognate and non-cognate amino
      acid substrates. Taking into account the peculiarities of non-cognate reactions,
      the specific controls needed and the dedicated experimental designs are discussed
      in detail. Kinetic partitioning within the synthetic and editing sites controls
      the balance between editing and aminoacylation. We describe in detail steady
      state and single-turnover approaches for the analysis of synthetic and editing
      reactions, which ultimately enable mechanisms of amino acid discrimination to be
      determined.

PMID- 27713081
TI  - TrackMate: An open and extensible platform for single-particle tracking.
AB  - We present TrackMate, an open source Fiji plugin for the automated, semi
      automated, and manual tracking of single-particles. It offers a versatile and
      modular solution that works out of the box for end users, through a simple and
      intuitive user interface. It is also easily scriptable and adaptable, operating
      equally well on 1D over time, 2D over time, 3D over time, or other single and
      multi-channel image variants. TrackMate provides several visualization and
      analysis tools that aid in assessing the relevance of results. The utility of
      TrackMate is further enhanced through its ability to be readily customized to
      meet specific tracking problems. TrackMate is an extensible platform where
      developers can easily write their own detection, particle linking, visualization
      or analysis algorithms within the TrackMate environment. This evolving framework
      provides researchers with the opportunity to quickly develop and optimize new
      algorithms based on existing TrackMate modules without the need of having to
      write de novo user interfaces, including visualization, analysis and exporting
      tools. The current capabilities of TrackMate are presented in the context of
      three different biological problems. First, we perform Caenorhabditis-elegans
      lineage analysis to assess how light-induced damage during imaging impairs its
      early development. Our TrackMate-based lineage analysis indicates the lack of a
      cell-specific light-sensitive mechanism. Second, we investigate the recruitment
      of NEMO (NF-kappaB essential modulator) clusters in fibroblasts after stimulation
      by the cytokine IL-1 and show that photodamage can generate artifacts in the
      shape of TrackMate characterized movements that confuse motility analysis.
      Finally, we validate the use of TrackMate for quantitative lifetime analysis of
      clathrin-mediated endocytosis in plant cells.

PMID- 27713082
TI  - Cytotoxic melodinus-type alkaloids from the ethanol extract of Melodinus
      fusiformis.
AB  - A chemical investigation of the ethanol extract of the aerial parts of Melodinus
      fusiformis led to the isolation of six new melodinus-type alkaloids, melofusines
      A-E (1-6), along with one known compound, melodinine B. Structural elucidation of
      all the compounds was performed by spectral methods such as 1D and 2D NMR, IR, UV
      and HRESIMS. The isolated compounds were tested in vitro for cytotoxic potential
      against six tumor cell lines (Hep-2, SCL-1, CAL-27, UMSCC-1, Detroit-562 and TCA
      83). As a result, compound 1 exhibited significant cytotoxic activities against
      all tested tumor cell lines with IC50 values <5MUM.

PMID- 27713083
TI  - The antihypercholesterolemic effect of columbamine from Rhizoma Coptidis in HFHC
      diet induced hamsters through HNF-4alpha/FTF-mediated CYP7A1 activation.
AB  - The aim of this study was to investigate the antihypercholesterolemic activity
      and potential molecular mechanism of columbamine (COL) that was prepared by
      extraction from Rhizoma Coptidis in hamsters and HepG2 cells. The results
      displayed that the COL from Rhizoma Coptidis was a safe natural compound with a
      LD50 0f 1524.6mg/kg and no detectable toxic symptoms during the observation of
      chronic toxicity. COL dose-dependently reversed the abnormal lipid levels induced
      by HFHC diet. Specifically, COL(M) and COL(H) significantly reduced the blood
      lipid levels(TC, TG and LDL-c) and enhanced the fecal contents of TBA by 21.8%
      and 25.1% respectively in hamsters. COL up-regulated the genes of CYP8B1, CYP7A1
      and LDLR in mRNA and protein level, and down-regulated those of HMGCR to a
      different degree. Especially, CYP7A1 were significantly up-regulated by COL in
      hamsters (p<0.01). Further analysis indicated that COL obviously activated the
      mRNA and protein expression of the transcription factors FTF, HNF-4alpha, and
      inhibited those of SHP. Promoter luciferase assay showed that COL induced the
      expression of FTF and HNF-4alpha, further transactivating CYP7A1, which
      accelerated the conversion of liver cholesterol to bile acids. It concluded that
      the COL showed high lipid-lowering activities through indirectly transactivating
      CYP7A1 by upregulating FTF and HNF-4alpha, and directly activating CYP7A1
      catalytic activity by strongly interacting with receptor and ligand, therefore
      promoting cholesterol catabolism and accelerating the excretion of bile acids.

PMID- 27713084
TI  - Pseudolaric acid B induces mitotic arrest and apoptosis in both 5-fluorouracil
      sensitive and -resistant colorectal cancer cells.
AB  - 5-fluorouracil (5-FU)-based chemotherapy is the main chemotherapeutic approach
      for colorectal cancer (CRC) treatment. Because chemoresistance occurs frequently
      and significantly limits CRC therapies, a novel agent is needed. Pseudolaric acid
      B (PAB), a small molecule derived from the Chinese medicinal herb ''Tujinpi'',
      exhibits strong cytotoxic effects on a variety of cancers. However, the detailed
      mechanisms by which PAB inhibits CRC cell growth and its potential role in
      overcoming 5-FU resistance have not been well studied. In this study, we showed
      that PAB significantly inhibited the viability of various CRC cell lines but
      induced minor cytotoxicity in normal cells. Both the in vitro and in vivo results
      showed that PAB induced proliferation inhibition, mitotic arrest and subsequently
      caspase-dependent apoptosis in both 5-FU-sensitive and -resistant CRC cells.
      Moreover, PAB was shown to interfere with CRC cell mitotic spindle apparatus and
      activate the spindle assembly checkpoint. Finally, CDK1 activity was involved in
      PAB-induced mitotic arrest and apoptosis in CRC cells. Taken together, these data
      reveal that PAB induces CRC cell mitotic arrest followed by apoptosis and
      overcomes 5-FU resistance in vitro and in vivo, suggesting that PAB may be a
      potential agent for CRC treatment, particularly for 5-FU-resistant CRC.

PMID- 27713085
TI  - The effect of high-fat diet consumption on appetitive instrumental behavior in
      rats.
AB  - Evidence now indicates that the chronic consumption of high-calorie foods, such
      as a high-fat diet (HFD), is associated with impaired control over food-seeking,
      yet the extent of this alteration is not fully understood. Using different
      reinforcement schedules, we evaluated whether HFD intake from weaning to
      adulthood modifies instrumental responding and induces a shift from goal-directed
      actions to habitual responding. We first observed reduced instrumental
      performance and motivation for a food reward in HFD-fed rats trained under
      schedules of reinforcement that facilitate habitual responding [Random Interval
      (RI)]. However, this deficit was alleviated if rats trained under RI were
      subsequently trained with reinforcement schedules that promote goal-directed
      strategies [Random Ratio (RR)]. Using an outcome devaluation procedure, we then
      demonstrated that consumption of a HFD promoted habitual behavior in rats trained
      under RI but not RR schedules. Finally, extended HFD exposure did not interfere
      with the ability of RR training to overcome impaired RI instrumental performance
      and to favor goal-directed behavior. These results indicate that chronic
      consumption of a HFD changes the co-ordination of goal-directed actions and
      habits and that alteration of food-seeking may be reversed under particular
      behavioral conditions.

PMID- 27713087
TI  - A nanovehicle developed for treating deep-seated bacteria using low-dose X-ray.
AB  - : Many non-antibiotic strategies, such as photocatalysis and photodynamic
      therapy, have been proposed to inhibit and/or kill bacteria. However, these
      approaches still have drawbacks such as insufficient bacterial specificity and
      the limited penetration depth of ultraviolet and near-infrared light. To overcome
      these limitations, we developed a bacteria-specific anti-bacterial technique via
      using low-dose X-ray. Graphene oxide quantum dots (GQDs, a multifunctional
      vehicle) conjugated with vancomycin (Van, a bacteria-targeting ligand) were
      assembled with Protoporphyrin IX (PpIX, a photo/radiation sensitizer) to yield a
      novel Van-GQDs/PpIX complex that specifically attached to Escherichia coli and
      efficiently generated intracellular reactive oxygen species following X-ray
      activation. Delivery using GQDs increased the PpIX/Van ratio in the target
      bacterial cell, damaged bacterial cell wall, and enhanced X-ray-induced PpIX
      activation. Hence, this approach allowed for the use of a low-dose X-ray to
      efficiently activate the Van-GQDs/PpIX complex to exert its bactericidal effects
      on Escherichia coli without damaging normal cells. Furthermore, the E. coli did
      not develop resistance to the proposed approach for at least 7 rounds of repeated
      administration during one week. Thus, this proposed vehicle exhibiting bacteria
      specific X-ray-triggered toxicity is a promising alternative to antibiotics for
      treating serious bacterial infections occurring in deep-seated tissues/organs
      (e.g., osteomyelitis and peritonitis). STATEMENTS OF SIGNIFICANCE: Administration
      of antibiotics is the most common treatment modality for bacterial infections.
      However, in some cases, patient attributes such as age, health, tolerance to
      antibiotics do not allow for the use of high-dose antibiotics. In addition, some
      bacteria develop resistance to antibiotics because of improper and long-term use
      of these agents. Therefore, non-antibiotic strategies to treat deeply situated
      bacterial infections, such as osteomyelitis, are urgently needed for avoiding
      amputation. To date, several non-antibiotic approaches, such as Ag nanoparticles,
      graphene-based materials, photocatalysis, and photodynamic therapy have been
      proposed to inhibit and/or kill bacteria. However, the major challenges of
      photochemical strategies, specificity and limited penetration depth of light
      source, still remain for treating the deep-seated bacteria. To overcome these
      problems, we developed a novel nanovehicle that exerted toxic effects
      specifically on bacteria following activation by a deeply penetrative low-dose X
      ray, without damaging normal cells. As such, it realizes a deeply photochemical
      route for treating the deep-seated bacteria.

PMID- 27713086
TI  - Silk-based biomaterials functionalized with fibronectin type II promotes cell
      adhesion.
AB  - : The objective of this work was to exploit the fibronectin type II (FNII) module
      from human matrix metalloproteinase-2 as a functional domain for the development
      of silk-based biopolymer blends that display enhanced cell adhesion properties.
      The DNA sequence of spider dragline silk protein (6mer) was genetically fused
      with the FNII coding sequence and expressed in Escherichia coli. The chimeric
      protein 6mer+FNII was purified by non-chromatographic methods. Films prepared
      from 6mer+FNII by solvent casting promoted only limited cell adhesion of human
      skin fibroblasts. However, the performance of the material in terms of cell
      adhesion was significantly improved when 6mer+FNII was combined with a silk
      elastin-like protein in a concentration-dependent behavior. With this work we
      describe a novel class of biopolymer that promote cell adhesion and potentially
      useful as biomaterials for tissue engineering and regenerative medicine.
      STATEMENT OF SIGNIFICANCE: This work reports the development of biocompatible
      silk-based composites with enhanced cell adhesion properties suitable for
      biomedical applications in regenerative medicine. The biocomposites were produced
      by combining a genetically engineered silk-elastin-like protein with a
      genetically engineered spider-silk-based polypeptide carrying the three domains
      of the fibronectin type II module from human metalloproteinase-2. These
      composites were processed into free-standing films by solvent casting and
      characterized for their biological behavior. To our knowledge this is the first
      report of the exploitation of all three FNII domains as a functional domain for
      the development of bioinspired materials with improved biological performance.
      The present study highlights the potential of using genetically engineered
      protein-based composites as a platform for the development of new bioinspired
      biomaterials.

PMID- 27713088
TI  - Comparison of three lymph node classifications for survival prediction in distant
      metastatic gastric cancer.
AB  - BACKGROUND: The optimal lymph node (LN) classification system for prognostic
      assessment in distant metastatic gastric cancer (DMGC) patients who undergo LN
      dissection remains unclear. Therefore, we compared the prognostic performance of
      positive LN (PLN), LN ratio (LNR), and log odds of positive LNs (LODDS) in DMGC
      patients. METHODS: A total of 1999 DMGC patients who underwent lymphadenectomy
      recorded in the Surveillance Epidemiology and End Results database from 2004 to
      2012 were reviewed. RESULTS: Univariate analyses showed that the PLN, LNR and
      LODDS systems were all significantly correlated with cancer-specific survival
      (CSS). However, only the LODDS classification remained an independent prognostic
      factor through the multivariate analysis. Furthermore, this classification could
      efficiently discriminate survival outcomes in patients within the same positive
      PLN category, as well as in patients with no positive node involvement. Both the
      LODDS and LNR classifications had better discriminatory ability, monotonicity,
      and homogeneity of prognostic stratification, as well as more accurate 1 or 2
      year CSS prediction, than the PLN classification. The performances of the LNR and
      LODDS classifications were similar. Additionally, we found that inclusion of PORT
      carried a survival benefit across all LODDS intervals except the "LODDS <= -1.0"
      subgroup. CONCLUSION: Our findings indicate that the LODDS classification is the
      most optimal system for prognostic assessment in DMGC patients. Incorporating
      LODDS into the staging system of DMGC patients will enable clinicians to more
      accurately predict prognosis and guide regional therapy regimen decisions in DMGC
      patients.

PMID- 27713089
TI  - The Fibrodysplasia Ossificans Progressiva (FOP) mutation p.R206H in ACVR1 confers
      an altered ligand response.
AB  - Patients with Fibrodysplasia Ossificans Progressiva (FOP) suffer from ectopic
      bone formation, which progresses during life and results in dramatic movement
      restrictions. Cause of the disease are point mutations in the Activin A receptor
      type 1 (ACVR1), with p.R206H being most common. In this study we compared the
      signalling responses of ACVR1WT and ACVR1R206H to different ligands. ACVR1WT, but
      not ACVR1R206H inhibited BMP signalling of BMP2 or BMP4 in a ligand binding
      domain independent manner. Likewise, the basal BMP signalling activity of the
      receptor BMPR1A or BMPR1B was inhibited by ACVR1WT, but enhanced by ACVR1R206H.
      In comparison, BMP6 or BMP7 activated ACVR1WT and caused a hyper-activation of
      ACVR1R206H. These effects were dependent on an intact ligand binding domain.
      Finally, the neofunction of Activin A in FOP was tested and found to depend on
      the ligand binding domain for activating ACVR1R206H. We conclude that the FOP
      mutation ACVR1R206H is more sensitive to a number of natural ligands. The mutant
      receptor apparently lost some essential inhibitory interactions with its ligands
      and co-receptors, thereby conferring an enhanced ligand-dependent signalling and
      stimulating ectopic bone formation as observed in the patients.

PMID- 27713090
TI  - A Comprehensive Assessment of Toxicities in Patients with Central Nervous System
      Lymphoma Undergoing Autologous Stem Cell Transplantation Using Thiotepa,
      Busulfan, and Cyclophosphamide Conditioning.
AB  - High-dose therapy and autologous stem cell transplantation (ASCT) with thiotepa,
      busulfan, and cyclophosphamide (TBC) conditioning has emerged as an effective
      postinduction treatment strategy for patients with primary central nervous system
      lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL), but it is
      associated with considerable toxicity and transplantation-related mortality (TRM)
      in the modern era. Forty-three adult patients with chemosensitive PCNSL or SCNSL
      underwent TBC-conditioned ASCT between 2006 and 2015. Twenty-eight of these
      patients received pharmacokinetically (PK)-targeted busulfan dosing. The median
      number of clinically relevant individual grade >=3 nonhematologic toxicities per
      patient was 5. We found no association between pretransplantation patient
      characteristics and the presence of more than 5 grade >=3 nonhematologic
      toxicities. Patients with elevated first-dose busulfan area under the curve
      values did not experience more toxicity. Paradoxically, patients treated with
      more than 2 regimens before undergoing ASCT had lower first-dose busulfan AUC
      values. With a median follow-up among survivors of 20 months, 1-year progression
      free survival (PFS) and overall survival (OS) from the time of ASCT were 83% and
      87%, respectively. Although this study reaffirms the favorable PFS and OS
      associated with TBC-conditioned ASCT for PCNSL or SCNSL, this treatment strategy
      carries a large toxicity burden.

PMID- 27713091
TI  - National Institutes of Health Blood and Marrow Transplant Late Effects
      Initiative: The Healthcare Delivery Working Group Report.
AB  - Hematopoietic cell transplantation (HCT) survivors are at risk for development of
      late complications and require lifelong monitoring for screening and prevention
      of late effects. There is an increasing appreciation of the issues related to
      healthcare delivery and coverage faced by HCT survivors. The 2016 National
      Institutes of Health Blood and Marrow Transplant Late Effects Initiative included
      an international and broadly representative Healthcare Delivery Working Group
      that was tasked with identifying research gaps pertaining to healthcare delivery
      and to identify initiatives that may yield a better understanding of the long
      term value and costs of care for HCT survivors. There is a paucity of literature
      in this area. Critical areas in need of research include pilot studies of novel
      and information technology supported models of care delivery and coverage for HCT
      survivors along with development and validation of instruments that capture
      patient-reported outcomes. Investment in infrastructure to support this research,
      such as linkage of databases including electronic health records and routine
      inclusion of endpoints that will inform analyses focused around care delivery and
      coverage, is required.

PMID- 27713093
TI  - Cross-generational effects of parental low dose BPA exposure on the Gonadotropin
      Releasing Hormone3 system and larval behavior in medaka (Oryzias latipes).
AB  - Growing evidence indicates that chronic exposure to Bisphenol A (BPA) may disrupt
      normal brain function and behavior mediated by gonadotropin-releasing hormone
      (GnRH) pathways. Previous studies have shown that low dose BPA (200ng/ml)
      exposure during embryogenesis altered development of extra-hypothalamic GnRH3
      systems and non-reproductive locomotor behavior in medaka. Effects of parental
      low-dose BPA exposure on the development of GnRH3 systems and locomotor behavior
      of offspring are not well known. This study examines whether the
      neurophysiological and behavioral effects of BPA in parents (F0 generation) are
      carried over to their offspring (F1 generation) using stable transgenic medaka
      embryos/larvae with GnRH3 neurons tagged with green fluorescent protein (GFP).
      Parental fish were exposed to BPA (200ng/ml) for either life-long or different
      developmental time windows. Fertilized F1 eggs were collected and raised in
      egg/fish water with no environmental exposure to BPA. All experiments were
      performed on F1 embryos/larvae, which were grouped based on the following
      parental (F0) BPA exposure conditions - (i) Group 1 (G1): through life; (ii) G2:
      during embryogenesis and early larval development [1-14days post fertilization
      (dpf)]; (iii) G3: during neurogenesis (1-5dpf); and (iv) G4: during sex
      differentiation (5-14dpf). Embryos from unexposed vehicle treated parents served
      as controls (G0). G1 embryos showed significantly reduced survival rates and
      delayed hatching time compared to other groups, while G4 embryos hatched
      significantly earlier than all other groups. At 3 dpf, the GnRH3-GFP intensity
      was increased by 47% in G3 embryos and decreased in G4 embryos by 59% compared to
      controls. At 4dpf, G1 fish showed 42% increased intensity, while GFP intensity
      was reduced by 44% in G3 subjects. In addition, the mean brain size of G1, G3 and
      G4 embryos were smaller than that of control at 4dpf. At 20dpf, all larvae from
      BPA-treated parents showed significantly decreased total movement (distance
      covered) compared with controls, with G2 and G3 fish showing reduced velocity of
      movement. While at 20 dpf no group differences were seen in the soma diameter of
      GnRH3-GFP neurons, a 34% decrease in SV2 expression, a marker for synaptic
      transmission, in G1 larvae was observed. These data suggest that parental BPA
      exposure during critical windows of embryonic development or chronic treatment
      affects next-generation offspring both in embryonic and larval brain development
      as well as larval behavior.

PMID- 27713094
TI  - Genetic variation associated with the occurrence and progression of neurological
      disorders.
AB  - This paper presents an overview of genetic variation associated with the onset
      and progression of 14 neurological disorders, focusing primarily on association
      studies. The 14 disorders are heterogeneous in terms of their frequency, age of
      onset, etiology and progression. There is substantially less evidence on
      progression than onset. With regard to onset, the conditions are diverse in terms
      of their epidemiology and patterns of familial aggregation. While the muscular
      dystrophies and Huntington's disease are monogenic diseases, for the other 12
      conditions only a small proportion of cases is associated with specific genetic
      syndromes or mutations. Excluding these, some familial aggregation remains for
      the majority of cases. There is considerable variation in the volume of evidence
      by condition, and by gene within condition. The volume of evidence is greatest
      for Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic
      lateral sclerosis. As for common complex chronic diseases, genome wide
      association studies have found that validated genomic regions account for a low
      proportion of heritability. Apart from multiple sclerosis, which shares several
      susceptibility loci with other immune-related disorders, variation at HLA-DRB5
      being associated both with Parkinson's disease and Alzheimer's disease, and the
      association of the C9orf72 repeat expansion with ALS and frontotemporal
      degeneration, there was little evidence of gene loci being consistently
      associated with more than one neurological condition or with other conditions.
      With the exception of spina bifida, for which maternal MTHFR genotype is
      associated with risk in the offspring, and corroborates other evidence of the
      importance of folate in etiology, there was little evidence that the pathways
      influenced by genetic variation are related to known lifestyle or environmental
      exposures.

PMID- 27713095
TI  - Nutrition for the ageing brain: Towards evidence for an optimal diet.
AB  - As people age they become increasingly susceptible to chronic and extremely
      debilitating brain diseases. The precise cause of the neuronal degeneration
      underlying these disorders, and indeed normal brain ageing remains however
      elusive. Considering the limits of existing preventive methods, there is a desire
      to develop effective and safe strategies. Growing preclinical and clinical
      research in healthy individuals or at the early stage of cognitive decline has
      demonstrated the beneficial impact of nutrition on cognitive functions. The
      present review is the most recent in a series produced by the Nutrition and
      Mental Performance Task Force under the auspice of the International Life
      Sciences Institute Europe (ILSI Europe). The latest scientific advances specific
      to how dietary nutrients and non-nutrient may affect cognitive ageing are
      presented. Furthermore, several key points related to mechanisms contributing to
      brain ageing, pathological conditions affecting brain function, and brain
      biomarkers are also discussed. Overall, findings are inconsistent and fragmented
      and more research is warranted to determine the underlying mechanisms and to
      establish dose-response relationships for optimal brain maintenance in different
      population subgroups. Such approaches are likely to provide the necessary
      evidence to develop research portfolios that will inform about new dietary
      recommendations on how to prevent cognitive decline.

PMID- 27713096
TI  - Regulation of Mitofusin1 by Mahogunin Ring Finger-1 and the proteasome modulates
      mitochondrial fusion.
AB  - Health and homoeostasis are maintained by a dynamic balance between mitochondrial
      fission and fusion. Mitochondrial fusion machinery is largely unknown in mammals.
      Only a few reports have illustrated the role of Fzo1 in mitochondrial fusion
      known in Saccharomyces cerevisiae. We demonstrate that the ubiquitin ligase
      Mahogunin Ring Finger-1 (MGRN1) interacts with and constitutively ubiquitinates
      the mammalian homolog, Mitofusin1 (Mfn1) via K63 linkages. In mice models, loss
      of Mgrn1 function leads to severe developmental defects and adult-onset
      spongiform neurodegeneration, similar to prion diseases. The tethering of
      mitochondria to form the ~180kDa Mfn1 complex is independent of MGRN1-mediated
      ubiquitination. However, successful mitochondrial fusion requires formation of
      higher oligomers of Mfn1 which in turn needs GTPase activity, intact heptad
      repeats of Mfn1 and ubiquitination by MGRN1. Following ubiquitination,
      proteasomal processing of Mfn1 completes the mitochondrial fusion process. This
      step requires functional p97 activity. These findings suggest a sequence of
      events where GTPase activity of Mfn1 and tethering of adjacent mitochondria
      precedes its MGRN1-mediated ubiquitination and proteasomal degradation
      culminating in mitochondrial fusion.

PMID- 27713097
TI  - Cytoplasmic RNA decay pathways - Enzymes and mechanisms.
AB  - RNA decay plays a crucial role in post-transcriptional regulation of gene
      expression. Work conducted over the last decades has defined the major mRNA decay
      pathways, as well as enzymes and their cofactors responsible for these processes.
      In contrast, our knowledge of the mechanisms of degradation of non-protein coding
      RNA species is more fragmentary. This review is focused on the cytoplasmic
      pathways of mRNA and ncRNA degradation in eukaryotes. The major 3' to 5' and 5'
      to 3' mRNA decay pathways are described with emphasis on the mechanisms of their
      activation by the deprotection of RNA ends. More recently discovered 3'-end
      modifications such as uridylation, and their relevance to cytoplasmic mRNA decay
      in various model organisms, are also discussed. Finally, we provide up-to-date
      findings concerning various pathways of non-coding RNA decay in the cytoplasm.

PMID- 27713098
TI  - First report on Babesia vogeli infection in dogs in the Philippines.
AB  - Babesia vogeli is a tick-borne protozoal pathogen that infects erythrocytes. In
      Southeast Asia, this pathogen has only been reported in Thailand. In this study,
      nine dogs presented at three different veterinary clinics in Cebu City,
      Philippines were found positive for B. vogeli. DNA was extracted from blood
      samples and tested using a PCR for genus Babesia and a PCR specific for B. vogeli
      (both based on the 18S rRNA gene). Blood smears (triplicate) from each sample
      were found negative. All positive amplicons were sequenced and were found to be
      99.4% identical to registered B. vogeli sequences at Genbank. Phylogenetic
      analysis revealed monophyletic grouping of Philippine sequences with the
      registered A. platys Genbank sequences. This is the first report of B. vogeli
      infection in dogs in the Philippines.

PMID- 27713099
TI  - Dispelling the myth: Exploring associations between the HPV vaccine and
      inconsistent condom use among college students.
AB  - Human papillomavirus (HPV) vaccination is safe and effective in preventing
      anogenital cancers and warts. However, myths have surrounded the HPV vaccine
      since its approval, including the possibility that HPV vaccinated young people
      are more likely to engage in risky sexual behaviors. The purpose of this study
      was to assess the association between HPV vaccination and engaging in
      inconsistent condom use in a sample of U.S. college students. A secondary data
      analysis of the National College Health Assessment-II (Fall 2013) was conducted
      in 2015. Risky sexual activity was operationalized as inconsistent condom use for
      oral, vaginal or anal sexual activity. Logistic regression models were stratified
      by sexual activity and gender, and controlled for socio-demographics and history
      of STIs. Inconsistent condom use was reported among females for vaginal (47%),
      oral (94%), and anal sex (75%); while males reported levels of inconsistency for
      vaginal (38%), oral (94%), and anal sex (58%). Sixty-nine percent of females
      reported receiving the HPV vaccine compared to 43% of males. Among females, there
      was no significant association between HPV vaccination and inconsistent condom
      use in any of the sexual activities. Among males, there was no significant
      association between HPV vaccination and inconsistent condom use in oral or
      vaginal sex. HPV-vaccinated males were less likely to report inconsistent condom
      use during anal sexual activity. This study contributes to the increasing
      evidence that HPV vaccination is not associated with risky sexual behavior.
      Dispelling this myth is important to facilitate uptake and completion of the HPV
      vaccine in the U.S.

PMID- 27713100
TI  - Do cigarette health warning labels comply with requirements: A 14-country study.
AB  - The Framework Convention on Tobacco Control, a global health treaty ratified by
      over 175 countries, calls on countries to ensure that tobacco packages carry
      health warning labels (HWLs) describing the harmful effects of tobacco use. We
      assessed the extent of compliance with 14 countries' HWL requirements. Unique
      cigarette packs were purchased in 2013 using a systematic protocol in 12 distinct
      neighborhoods within three of the ten most populous cities in the 14 low- and
      middle-income countries with the greatest number (count) of smokers. HWL
      compliance codebooks were developed for each country based on the details of
      country-specific HWL requirements, with up to four common compliance indicators
      assessed for each country (location, size, label elements, text size). Packs
      (n=1859) were double coded for compliance. Compliance was examined by country and
      pack characteristics, including parent company and brand family. Overall, 72% of
      coded cigarette packs were compliant with all relevant compliance indicators,
      ranging from 17% in the Philippines to 94% in Mexico. Compliance was highest for
      location of the warning (ranging from 75%-100%) and lowest for warning size
      (ranging from 46%-99%). Compliance was higher for packs bought in high SES
      neighborhoods, and varied by parent company and brand family. This multi-country
      study found at least one pack in every country - and many packs in some countries
      - that were not compliant with key requirements for health warning labels in the
      country of purchase. Non-compliance may be exacerbating health disparities.
      Tobacco companies should be held accountable for complying with country HWL
      requirements.

PMID- 27713092
TI  - The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the
      National Institutes of Health Consensus Development Project on Criteria for
      Clinical Trials in Chronic Graft-versus-Host Disease.
AB  - Chronic graft-versus-host disease (GVHD) is the leading cause of late, nonrelapse
      mortality and disability in allogeneic hematopoietic cell transplantation
      recipients and a major obstacle to improving outcomes. The biology of chronic
      GVHD remains enigmatic, but understanding the underpinnings of the immunologic
      mechanisms responsible for the initiation and progression of disease is
      fundamental to developing effective prevention and treatment strategies. The
      goals of this task force review are as follows: This document is intended as a
      review of our understanding of chronic GVHD biology and therapies resulting from
      preclinical studies, and as a platform for developing innovative clinical
      strategies to prevent and treat chronic GVHD.

PMID- 27713101
TI  - Cardiorespiratory fitness levels and moderators in people with HIV: A systematic
      review and meta-analysis.
AB  - Cardiorespiratory fitness (CRF) is a modifiable risk factor for cardiovascular
      disease and premature mortality. CRF levels and moderators among people living
      with HIV (PLWH) are unknown. The aim of the current meta-analysis was to (1)
      determine mean CRF in PLWH and compare levels with age- and gender-matched
      healthy controls (HCs), (2) explore moderators of CRF, (3) and (4) explore
      moderators of CRF outcomes following physical activity (PA) interventions. Major
      electronic databases were searched systematically for articles reporting CRF
      expressed as maximum or peak oxygen uptake (ml/min/kg) in PLWH. A random effects
      meta-analysis calculating the pooled mean CRF including subgroup- and meta
      regression analyses was undertaken. Across 21 eligible studies, the CRF level was
      26.4ml/kg/min (95% CI=24.6 to 28.1) (n=1010; mean age=41years). There were
      insufficient data to compare CRF levels with HCs. A higher body mass index (beta=
      0.99, 95% CI=-1.93 to -0.06, P=0.04), older age (beta=-0.31, 95% CI=-0.58 to 
      0.04, P=0.02) and the presence of lipodystrophy (beta=-4.63, 95% CI=-7.88 to 
      1.39, P=0.005) were significant moderators of lower CRF levels. Higher CD4+
      counts (beta=0.004, 95% CI=0.0007 to 0.007, P=0.016), supervised interventions
      (P<0.001) and interventions with a lower frequency of weekly sessions (2 or 3
      versus 4 times) (P<0.001) predicted a better CRF-outcome following PA. CRF levels
      of PLWH are among the lowest in comparison to other vulnerable populations. More
      research on the most optimal physical activity intervention characteristics is
      needed.

PMID- 27713102
TI  - Pedestrian-oriented zoning is associated with reduced income and poverty
      disparities in adult active travel to work, United States.
AB  - : Active travel to work can provide additional minutes of daily physical
      activity. While the literature points to the relationship between zoning, equity
      and socioeconomic status, and physical activity, no study has quantitatively
      explored these connections. This study examined whether zoning may help to
      moderate any income and poverty inequities in active travel and taking public
      transit to work. Research was conducted between May 2012 and June 2015. Zoning
      data were compiled for 3914 jurisdictions covering 45.45% of the U.S. population
      located in 471 of the most populous U.S. counties and 2 consolidated cities
      located in 48 states and the District of Columbia. (Sensitivity analyses also
      captured unincorporated areas which, with the municipalities, collectively
      covered ~72% of the U.S. POPULATION: ) Zoning codes were obtained and evaluated
      to assess the pedestrian-orientation of the zoning codes. Public transit use,
      active travel to work, median household income, and poverty data were obtained
      for all study jurisdictions from the 2010-2014 American Community Survey
      estimates. Associations were examined through multivariate regression models,
      controlling for community sociodemographics, clustered on county, with robust
      standard errors. We found that certain pedestrian-oriented zoning provisions
      (e.g., crosswalks, bike-pedestrian connectivity, street connectivity, bike lanes,
      bike parking, and more zoning provisions) were associated with reduced income
      and/or poverty disparities in rates of public transit use and active travel to
      work. Findings from this study can help to inform cross-sectoral collaborations
      between the public health, planning, and transportation fields regarding zoning
      for pedestrian-orientation and active travel.

PMID- 27713103
TI  - Burden of skin cancer in Belgium and cost-effectiveness of primary prevention by
      reducing ultraviolet exposure.
AB  - Skin cancer (melanoma- and non-melanoma skin cancer) is one of the most rapidly
      increasing cancers worldwide. This study analysed the current and future economic
      burden of skin cancer in Belgium and the cost-effectiveness of primary prevention
      of skin cancer. A retrospective bottom-up cost-of-illness study was performed,
      together with a Markov model in order to analyse the cost-effectiveness and the
      budget impact analysis of primary prevention of skin cancer in Belgium. Total
      prevalence of skin cancer in Belgium was estimated to triple in the next 20years.
      The total economic burden of skin cancer in 2014 in Belgium was estimated at ?106
      million, with a cumulative cost of ?3 billion in 2034. The majority of this total
      cost was due to melanoma (65%). Over a period of 50years, both a sensitisation
      campaign and a total ban on sunbed use would lead to a gain in quality-adjusted
      life-years and cost-savings. For every euro invested in the campaign, ?3.6 would
      be saved on the long-term for the healthcare payer. Policy makers and clinicians
      should promote UV protection strategies, as they were estimated to be dominant
      strategies.

PMID- 27713104
TI  - Quantitative morphometric study of the subaxial cervical vertebrae end plate.
AB  - BACKGROUND CONTEXT: Cervical disc arthroplasty has been gradually adopted as an
      alternative for the treatment of cervical degenerative disease. However, there is
      a large discrepancy between footprints of currently available cervical disc
      prostheses and anatomic dimensions of cervical end plates. PURPOSE: This study
      aimed to accurately and comprehensively quantify the three-dimensional (3D)
      anatomic morphology of the cervical vertebral end plate and provide a theoretical
      basis for designing appropriate disc prostheses. Moreover, we introduced a novel
      geometric and mechanical model for 3D reconstruction techniques of the cervical
      end plate. STUDY DESIGN: A descriptive study of the geometry of the middle and
      lower cervical vertebral end plates in cadaveric spines was carried out. METHODS:
      A total of 138 cervical vertebral end plates were digitized using an optical 3D
      range scanning system, and then each end plate was reconstructed using the
      digitized image. For each end plate, the morphologic characteristics of six
      surface curves and the end plate concavity depth were symmetrically chosen and
      depicted. RESULTS: The cranial end plates (relative to the disc) were concave and
      the caudal end plates were relatively flat at all disc levels, with mean
      concavity depths of 2.04 and 0.69 mm, respectively. For the caudal end plates,
      the end plate concavity apex was most often (81.42%) located in the posterior
      portion, whereas in the cranial end plates, the distribution was relatively even.
      For the sagittal curves, the foremost point and the rearmost point on the middle
      curve had a more forward position than those in the left curve and the right
      curve. Regarding the frontal plane curves, the length of the middle curve was
      longer than that of the anterior curve and posterior curve. For the cranial end
      plate, the maximal mean depth was the middle curve, whereas for the caudal end
      plate, the maximum depth was the posterior curve. CONCLUSIONS: There is marked
      morphologic asymmetry, in that the cranial end plate is more concave than the
      corresponding caudal end plate. In the sagittal plane, the caudal end plates are
      aerofoil-shaped, whereas the cranial end plates are arc-shaped. In the transverse
      plane, the end plates are kidney-shaped. These morphologic characteristics of
      cervical vertebral end plates should be taken into consideration when designing
      cervical devices, such as artificial discs.

PMID- 27713105
TI  - Associations between Long-Term Particulate Matter Exposure and Adult Renal
      Function in the Taipei Metropolis.
AB  - BACKGROUND: Studies on the effect of air pollutions on kidney diseases are still
      limited. OBJECTIVE: We aimed to investigate the associations between particulate
      matter (PM) exposures and renal function among adults. METHODS: We recruited
      21,656 adults as participants from 2007 to 2009. The Taiwanese Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) equation was used to derive the
      estimated glomerular filtration rate (eGFR). Subjects with an eGFR lower than 60
      mL/min/1.73 m2 were defined as having chronic kidney disease (CKD). Land use
      regression (LUR) models were used to estimate individual exposures to PM with an
      aerodynamic diameter < 10 MUm (PM10), coarse particles (PMCoarse), fine particles
      (PM2.5), and PM2.5Absorbance. Generalized linear and logistic regression models
      were used to estimate the associations between PM exposure and renal function.
      RESULTS: An IQR increase in PM10 (5.83 MUg/m3) was negatively associated with
      eGFR by -0.69 (95% CI: -0.89, -0.48) mL/min/1.73 m2 and positively associated
      with the prevalence of CKD with adjusted OR = 1.15 (95% CI: 1.07, 1.23). An IQR
      increase in PMCoarse (6.59 MUg/m3) was significantly associated with lower eGFR
      by -1.07 (95% CI: -1.32, -0.81) mL/min/1.73 m2 and CKD with OR = 1.26 (95% CI:
      1.15, 1.38). In contrast, neither outcome was significantly associated with PM2.5
      or PM2.5Absorbance. Stratified analyses indicated that associations of CKD with
      both PM10 and PMCoarse were limited to participants < 65 years of age, and were
      stronger (for PM10) or limited to (PMCoarse) women. Associations also appeared to
      be stronger in those without (vs. with) hypertension, and in normal versus
      overweight participants. CONCLUSIONS: Exposure during the previous year to PM10
      and PMCoarse, but not PM2.5 or PM2.5Absorbance, was associated with reduced renal
      function among Taiwanese adults.

PMID- 27713106
TI  - An Analysis of the Potential Impact of Climate Change on Dengue Transmission in
      the Southeastern United States.
AB  - BACKGROUND: Dengue fever, caused by a mosquito-transmitted virus, is an
      increasing health concern in the Americas. Meteorological variables such as
      temperature and precipitation can affect disease distribution and abundance
      through biophysical impacts on the vector and on the virus. Such tightly coupled
      links may facilitate further spread of dengue fever under a changing climate. In
      the southeastern United States, the dengue vector is widely established and
      exists on the current fringe of dengue transmission. OBJECTIVES: We assessed
      projected climate change-driven shifts in dengue transmission risk in this
      region. METHODS: We used a dynamic mosquito population and virus transmission
      model driven by meteorological data to simulate Aedes aegypti populations and
      dengue cases in 23 locations in the southeastern United States under current
      climate conditions and future climate projections. We compared estimates for each
      location with simulations based on observed data from San Juan, Puerto Rico,
      where dengue is endemic. RESULTS: Our simulations based on current climate data
      suggest that dengue transmission at levels similar to those in San Juan is
      possible at several U.S. locations during the summer months, particularly in
      southern Florida and Texas. Simulations that include climate change projections
      suggest that conditions may become suitable for virus transmission in a larger
      number of locations and for a longer period of time during each year. However, in
      contrast with San Juan, U.S. locations would not sustain year-round dengue
      transmission according to our model. CONCLUSIONS: Our findings suggest that
      Dengue virus (DENV) transmission is limited by low winter temperatures in the
      mainland United States, which are likely to prevent its permanent establishment.
      Although future climate conditions may increase the length of the mosquito season
      in many locations, projected increases in dengue transmission are limited to the
      southernmost locations.

PMID- 27713107
TI  - A Longitudinal Study of Peripubertal Serum Organochlorine Concentrations and
      Semen Parameters in Young Men: The Russian Children's Study.
AB  - BACKGROUND: Exposures to endocrine-disrupting chemicals during critical phases of
      testicular development may be related to poorer semen parameters. However, few
      studies have assessed the association between childhood organochlorine (OC)
      exposure and adult semen parameters. OBJECTIVE: We examined whether peripubertal
      serum OC concentrations are associated with semen parameters among young Russian
      men. METHODS: From 2003 through 2005, 516 boys were enrolled at age 8-9 years and
      followed for up to 10 years. Serum OCs were measured in the enrollment samples
      using high-resolution mass spectrometry. At 18-19 years, 133 young men provided 1
      or 2 semen samples (256 samples) collected approximately 1 week apart, which were
      analyzed for volume, sperm concentration, and motility. Unadjusted and adjusted
      linear mixed models were used to examine the associations of quartiles of lipid
      standardized concentrations of dioxins [2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), polychlorinated dibenzo-p-dioxins (PCDDs)], furans, polychlorinated
      biphenyls (PCBs), and corresponding toxic equivalents (TEQs) with semen
      parameters. RESULTS: The median (range) for TCDD was 2.9 (0.4-12.1) pg/g lipid
      and PCDD TEQ was 8.7 (1.0-36.0) pg TEQ/g lipid. Higher quartiles of TCDD and PCDD
      TEQs were associated with lower sperm concentration, total sperm count, and total
      motile sperm count (p-trends <= 0.05). The highest quartile of peripubertal serum
      TCDD concentrations was associated with a decrease (95% CI) of 40% (18, 66%), 29%
      (3, 64%), and 30% (2, 70%) in sperm concentration, total sperm count, and total
      motile sperm count, respectively, compared with the lowest quartile. Similar
      associations were observed for serum PCDD TEQs with semen parameters. Serum PCBs,
      furans, and total TEQs were not associated with semen parameters. CONCLUSION:
      Higher peripubertal serum TCDD concentrations and PCDD TEQs were associated with
      poorer semen parameters. Citation: Minguez-Alarcon L, Sergeyev O, Burns JS,
      Williams PL, Lee MM, Korrick SA, Smigulina L, Revich B, Hauser R. 2017. A
      longitudinal study of peripubertal serum organochlorine concentrations and semen
      parameters in young men: the Russian Children's Study. Environ Health Perspect
      125:460-466; http://dx.doi.org/10.1289/EHP25.

PMID- 27713109
TI  - Population-Level Exposure to Particulate Air Pollution during Active Travel:
      Planning for Low-Exposure, Health-Promoting Cities.
AB  - BACKGROUND: Providing infrastructure and land uses to encourage active travel
      (i.e., bicycling and walking) are promising strategies for designing health
      promoting cities. Population-level exposure to air pollution during active travel
      is understudied. OBJECTIVES: Our goals were a) to investigate population-level
      patterns in exposure during active travel, based on spatial estimates of bicycle
      traffic, pedestrian traffic, and particulate concentrations; and b) to assess how
      those exposure patterns are associated with the built environment. METHODS: We
      employed facility-demand models (active travel) and land use regression models
      (particulate concentrations) to estimate block-level (n = 13,604) exposure during
      rush-hour (1600-1800 hours) in Minneapolis, Minnesota. We used the model-derived
      estimates to identify land use patterns and characteristics of the street network
      that are health promoting. We also assessed how exposure is correlated with
      indicators of health disparities (e.g., household income, proportion of nonwhite
      residents). Our work uses population-level rates of active travel (i.e., traffic
      flows) rather than the probability of walking or biking (i.e., "walkability" or
      "bikeability") to assess exposure. RESULTS: Active travel often occurs on high
      traffic streets or near activity centers where particulate concentrations are
      highest (i.e., 20-42% of active travel occurs on blocks with high population
      level exposure). Only 2-3% of blocks (3-8% of total active travel) are "sweet
      spots" (i.e., high active travel, low particulate concentrations); sweet spots
      are located a) near but slightly removed from the city-center or b) on off-street
      trails. We identified 1,721 blocks (~ 20% of local roads) where shifting active
      travel from high-traffic roads to adjacent low-traffic roads would reduce
      exposure by ~ 15%. Active travel is correlated with population density, land use
      mix, open space, and retail area; particulate concentrations were mostly
      unchanged with land use. CONCLUSIONS: Public health officials and urban planners
      may use our findings to promote healthy transportation choices. When designing
      health-promoting cities, benefits (physical activity) as well as hazards (air
      pollution) should be evaluated.

PMID- 27713108
TI  - Chronic Exposure to Low Doses of Dioxin Promotes Liver Fibrosis Development in
      the C57BL/6J Diet-Induced Obesity Mouse Model.
AB  - BACKGROUND: Exposure to persistent organic pollutants (POPs) has been associated
      with the progression of chronic liver diseases, yet the contribution of POPs to
      the development of fibrosis in non-alcoholic fatty liver disease (NAFLD), a
      condition closely linked to obesity, remains poorly documented. OBJECTIVES: We
      investigated the effects of subchronic exposure to low doses of the POP 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor ligand, on NAFLD
      progression in diet-induced obese C57BL/6J mice. METHODS: Male C57BL/6J mice were
      fed either a 10% low-fat (LFD) or a 45% high-fat (HFD) purified diet for 14 weeks
      and TCDD-exposed groups were injected once a week with 5 MUg/kg TCDD or the
      vehicle for the last 6 weeks of the diet. RESULTS: Liver histology and
      triglyceride levels showed that exposure of HFD fed mice to TCDD worsened hepatic
      steatosis, as compared to either HFD alone or LFD plus TCDD and the mRNA levels
      of key genes of hepatic lipid metabolism were strongly altered in co-treated
      mice. Further, increased liver collagen staining and serum transaminase levels
      showed that TCDD induced liver fibrosis in the HFD fed mice. TCDD in LFD fed mice
      increased the expression of several inflammation and fibrosis marker genes with
      no additional effect from a HFD. CONCLUSIONS: Exposure to TCDD amplifies the
      impairment of liver functions observed in mice fed an enriched fat diet as
      compared to a low fat diet. The results provide new evidence that environmental
      pollutants promote the development of liver fibrosis in obesity-related NAFLD in
      C57BL/6J mice. Citation: Duval C, Teixeira-Clerc F, Leblanc AF, Touch S, Emond C,
      Guerre-Millo M, Lotersztajn S, Barouki R, Aggerbeck M, Coumoul X. 2017. Chronic
      exposure to low doses of dioxin promotes liver fibrosis development in the
      C57BL/6J diet-induced obesity mouse model. Environ Health Perspect 125:428-436;
      http://dx.doi.org/10.1289/EHP316.

PMID- 27713110
TI  - Associations between Environmental Quality and Mortality in the Contiguous United
      States, 2000-2005.
AB  - BACKGROUND: Assessing cumulative effects of the multiple environmental factors
      influencing mortality remains a challenging task. OBJECTIVES: This study aimed to
      examine the associations between cumulative environmental quality and all-cause
      and leading cause-specific (heart disease, cancer, and stroke) mortality rates.
      METHODS: We used the overall Environmental Quality Index (EQI) and its five
      domain indices (air, water, land, built, and sociodemographic) to represent
      environmental exposure. Associations between the EQI and mortality rates (CDC
      WONDER) for counties in the contiguous United States (n = 3,109) were
      investigated using multiple linear regression models and random intercept and
      random slope hierarchical models. Urbanicity, climate, and a combination of the
      two were used to explore the spatial patterns in the associations. RESULTS: We
      found 1 standard deviation increase in the overall EQI (worse environment) was
      associated with a mean 3.22% (95% CI: 2.80%, 3.64%) increase in all-cause
      mortality, a 0.54% (95% CI: -0.17%, 1.25%) increase in heart disease mortality, a
      2.71% (95% CI: 2.21%, 3.22%) increase in cancer mortality, and a 2.25% (95% CI:
      1.11%, 3.39%) increase in stroke mortality. Among the environmental domains, the
      associations ranged from -1.27% (95% CI: -1.70%, -0.84%) to 3.37% (95% CI: 2.90%,
      3.84%) for all-cause mortality, -2.62% (95% CI: -3.52%, -1.73%) to 4.50% (95% CI:
      3.73%, 5.27%) for heart disease mortality, -0.88% (95% CI: -2.12%, 0.36%) to
      3.72% (95% CI: 2.38%, 5.06%) for stroke mortality, and -0.68% (95% CI: -1.19%, 
      0.18%) to 3.01% (95% CI: 2.46%, 3.56%) for cancer mortality. Air had the largest
      associations with all-cause, heart disease, and cancer mortality, whereas the
      sociodemographic index had the largest association with stroke mortality. Across
      the urbanicity gradient, no consistent trend was found. Across climate regions,
      the associations ranged from 2.29% (95% CI: 1.87%, 2.72%) to 5.30% (95% CI:
      4.30%, 6.30%) for overall EQI, and larger associations were generally found in
      dry areas for both overall EQI and domain indices. CONCLUSIONS: These results
      suggest that poor environmental quality, particularly poor air quality, was
      associated with increased mortality and that associations vary by urbanicity and
      climate region. Citation: Jian Y, Messer LC, Jagai JS, Rappazzo KM, Gray CL,
      Grabich SC, Lobdell DT. 2017. Associations between environmental quality and
      mortality in the contiguous United States, 2000-2005. Environ Health Perspect
      125:355-362; http://dx.doi.org/10.1289/EHP119.

PMID- 27713111
TI  - Air Pollution and Deaths among Elderly Residents of Sao Paulo, Brazil: An
      Analysis of Mortality Displacement.
AB  - BACKGROUND: Evaluation of short-term mortality displacement is essential to
      accurately estimate the impact of short-term air pollution exposure on public
      health. OBJECTIVES: We quantified mortality displacement by estimating single-day
      lag effects and cumulative effects of air pollutants on mortality using
      distributed lag models. METHODS: We performed a daily time series of
      nonaccidental and cause-specific mortality among elderly residents of Sao Paulo,
      Brazil, between 2000 and 2011. Effects of particulate matter smaller than 10 MUm
      (PM10), nitrogen dioxide (NO2) and carbon monoxide (CO) were estimated in Poisson
      generalized additive models. Single-day lag effects of air pollutant exposure
      were estimated for 0-, 1- and 2-day lags. Distributed lag models with lags of 0
      10, 0-20 and 0-30 days were used to assess mortality displacement and potential
      cumulative exposure effects. RESULTS: PM10, NO2 and CO were significantly
      associated with nonaccidental and cause-specific deaths in both single-day lag
      and cumulative lag models. Cumulative effect estimates for 0-10 days were larger
      than estimates for single-day lags. Cumulative effect estimates for 0-30 days
      were essentially zero for nonaccidental and circulatory deaths but remained
      elevated for respiratory and cancer deaths. CONCLUSIONS: We found evidence of
      mortality displacement within 30 days for nonaccidental and circulatory deaths in
      elderly residents of Sao Paulo. We did not find evidence of mortality
      displacement within 30 days for respiratory or cancer deaths. Citation: Costa AF,
      Hoek G, Brunekreef B, Ponce de Leon AC. 2017. Air pollution and deaths among
      elderly residents of Sao Paulo, Brazil: an analysis of mortality displacement.
      Environ Health Perspect 125:349-354; http://dx.doi.org/10.1289/EHP98.

PMID- 27713112
TI  - Developing a Health Information Technology Systems Matrix: A Qualitative
      Participatory Approach.
AB  - BACKGROUND: The US Department of Veterans Affairs (VA) has developed various
      health information technology (HIT) resources to provide accessible veteran
      centered health care. Currently, the VA is undergoing a major reorganization of
      VA HIT to develop a fully integrated system to meet consumer needs. Although
      extensive system documentation exists for various VA HIT systems, a more
      centralized and integrated perspective with clear documentation is needed in
      order to support effective analysis, strategy, planning, and use. Such a tool
      would enable a novel view of what is currently available and support identifying
      and effectively capturing the consumer's vision for the future. OBJECTIVE: The
      objective of this study was to develop the VA HIT Systems Matrix, a novel tool
      designed to describe the existing VA HIT system and identify consumers' vision
      for the future of an integrated VA HIT system. METHODS: This study utilized an
      expert panel and veteran informant focus groups with self-administered surveys.
      The study employed participatory research methods to define the current system
      and understand how stakeholders and veterans envision the future of VA HIT and
      interface design (eg, look, feel, and function). Directed content analysis was
      used to analyze focus group data. RESULTS: The HIT Systems Matrix was developed
      with input from 47 veterans, an informal caregiver, and an expert panel to
      provide a descriptive inventory of existing and emerging VA HIT in four
      worksheets: (1) access and function, (2) benefits and barriers, (3) system
      preferences, and (4) tasks. Within each worksheet is a two-axis inventory. The
      VA's existing and emerging HIT platforms (eg, My HealtheVet, Mobile Health,
      VetLink Kiosks, Telehealth), My HealtheVet features (eg, Blue Button, secure
      messaging, appointment reminders, prescription refill, vet library, spotlight,
      vitals tracker), and non-VA platforms (eg, phone/mobile phone, texting, non-VA
      mobile apps, non-VA mobile electronic devices, non-VA websites) are organized by
      row. Columns are titled with thematic and functional domains (eg, access,
      function, benefits, barriers, authentication, delegation, user tasks). Cells for
      each sheet include descriptions and details that reflect factors relevant to
      domains and the topic of each worksheet. CONCLUSIONS: This study provides
      documentation of the current VA HIT system and efforts for consumers' vision of
      an integrated system redesign. The HIT Systems Matrix provides a consumer
      preference blueprint to inform the current VA HIT system and the vision for
      future development to integrate electronic resources within VA and beyond with
      non-VA resources. The data presented in the HIT Systems Matrix are relevant for
      VA administrators and developers as well as other large health care organizations
      seeking to document and organize their consumer-facing HIT resources.

PMID- 27713113
TI  - A Web-Based Psychosocial Intervention for Family Caregivers of Older People:
      Results from a Mixed-Methods Study in Three European Countries.
AB  - BACKGROUND: Informal caregiving is the main source of care for older people in
      Europe. An enormous amount of responsibility and care activity is on the
      shoulders of family caregivers, who might experience problems in their
      psychological well-being and in reconciling caregiving and their personal sphere.
      In order to alleviate such burden, there is increasing interest and growing
      research in Europe on Web-based support addressing family caregivers and their
      needs. However, the level of development and penetration of innovative Web-based
      services for caregivers is still quite low and the access to traditional face-to
      face services can be problematic for logistic, availability, and quality reasons.
      OBJECTIVE: As part of the European project INNOVAGE, a pilot study was conducted
      for developing and testing a Web-based psychosocial intervention aimed at
      empowering family caregivers of older people in Italy, Sweden, and Germany. The
      program offered information resources and interactive services to enable both
      professional and peer support. METHODS: A mixed-methods, sequential explanatory
      design was adopted. Caregivers' psychological well-being, perceived negative and
      positive aspects of caregiving, and social support received were assessed before
      and after the 3-month intervention. Poststudy, a subsample of users participated
      in focus groups to assist in the interpretation of the quantitative results.
      RESULTS: A total of 94 out of 118 family caregivers (79.7%) from the three
      countries used the Web platform at least once. The information resources were
      used to different extents in each country, with Italian users having the lowest
      median number of visits (5, interquartile range [IQR] 2-8), whereas German users
      had the highest number (17, IQR 7-66) (P<.001). The interactive services most
      frequently accessed (more than 12 times) in all countries were the social network
      (29/73, 40%) and private messages (27/73, 37%). The pretest-posttest analysis
      revealed some changes, particularly the slight worsening of perceived positive
      values of caregiving (Carers of Older People in Europe [COPE] positive value
      subscale: P=.02) and social support received (COPE quality-of-support subscale:
      P=.02; Multidimensional Scale of Perceived Social Support subscale: P=.04), in
      all cases with small effect size (r range -.15 to -.18). Focus groups were
      conducted with 20 family caregivers and the content analysis of discussions
      identified five main themes: online social support, role awareness, caregiving
      activities, psychological well-being, and technical concerns. The analysis
      suggested the intervention was useful and appropriate, also stimulating a better
      self-efficacy and reappraisal of the caregivers' role. CONCLUSIONS: The
      intervention seemed to contribute to the improvement of family caregivers'
      awareness, efficacy, and empowerment, which in turn may lead to a better self
      recognition of their own needs and improved efforts for developing and accessing
      coping resources. A major implication of the study was the finalization and
      implementation of the InformCare Web platform in 27 European countries, now
      publicly accessible (www.eurocarers.org/informcare).

PMID- 27713114
TI  - Influence of Pedometer Position on Pedometer Accuracy at Various Walking Speeds:
      A Comparative Study.
AB  - BACKGROUND: Demographic growth in conjunction with the rise of chronic diseases
      is increasing the pressure on health care systems in most OECD countries.
      Physical activity is known to be an essential factor in improving or maintaining
      good health. Walking is especially recommended, as it is an activity that can
      easily be performed by most people without constraints. Pedometers have been
      extensively used as an incentive to motivate people to become more active.
      However, a recognized problem with these devices is their diminishing accuracy
      associated with decreased walking speed. The arrival on the consumer market of
      new devices, worn indifferently either at the waist, wrist, or as a necklace,
      gives rise to new questions regarding their accuracy at these different
      positions. OBJECTIVE: Our objective was to assess the performance of 4 pedometers
      (iHealth activity monitor, Withings Pulse O2, Misfit Shine, and Garmin vivofit)
      and compare their accuracy according to their position worn, and at various
      walking speeds. METHODS: We conducted this study in a controlled environment with
      21 healthy adults required to walk 100 m at 3 different paces (0.4 m/s, 0.6 m/s,
      and 0.8 m/s) regulated by means of a string attached between their legs at the
      level of their ankles and a metronome ticking the cadence. To obtain baseline
      values, we asked the participants to walk 200 m at their own pace. RESULTS: A
      decrease of accuracy was positively correlated with reduced speed for all
      pedometers (12% mean error at self-selected pace, 27% mean error at 0.8 m/s, 52%
      mean error at 0.6 m/s, and 76% mean error at 0.4 m/s). Although the position of
      the pedometer on the person did not significantly influence its accuracy, some
      interesting tendencies can be highlighted in 2 settings: (1) positioning the
      pedometer at the waist at a speed greater than 0.8 m/s or as a necklace at
      preferred speed tended to produce lower mean errors than at the wrist position;
      and (2) at a slow speed (0.4 m/s), pedometers worn at the wrist tended to produce
      a lower mean error than in the other positions. CONCLUSIONS: At all positions,
      all tested pedometers generated significant errors at slow speeds and therefore
      cannot be used reliably to evaluate the amount of physical activity for people
      walking slower than 0.6 m/s (2.16 km/h, or 1.24 mph). At slow speeds, the better
      accuracy observed with pedometers worn at the wrist could constitute a valuable
      line of inquiry for the future development of devices adapted to elderly people.

PMID- 27713115
TI  - A comprehensive transcriptomic analysis of differentiating embryonic stem cells
      in response to the overexpression of Mesogenin 1.
AB  - The mutation of somitogenesis protein Mesogenin 1 (Msgn1) has been widely used to
      study the direct link between somitogenesis and the development of an embryo.
      Several studies have used gene expression profiling of somitogenesis to identify
      the key genes in the process, but few have focused on the pathways involved and
      the coexpression patterns of associated pathways. Here we employed time-course
      microarray datasets of differentiating embryonic stem cells by overexpressing the
      transcription factor Msgn1 from the public database library of Gene Expression
      Omnibus (GEO). Then we applied gene set enrichment analysis (GSEA) to the
      datasets and performed candidate transcription factors selection. As a result,
      several significantly regulated pathways and transcription factors (TFs), as well
      as some of the specific signaling pathways, were identified during somitogenesis
      under Msgn1 overexpression, most of which had not been reported previously.
      Finally, significant core genes such as Hes1 and Notch1 as well as some of the
      TFs such as PPARs and FOXs were identified to construct coexpression networks of
      related pathways, the expression patterns of which had been validated by our
      following quantitative real-time PCR (qRT-PCR). The results of our study may help
      us better understand the molecular mechanisms of somitogenesis in mice at the
      genome-wide level.

PMID- 27713116
TI  - Prostate-specific membrane antigen (PSMA) assembles a macromolecular complex
      regulating growth and survival of prostate cancer cells "in vitro" and
      correlating with progression "in vivo".
AB  - The expression of Prostate Specific-Membrane Antigen (PSMA) increases in high
      grade prostate carcinoma envisaging a role in growth and progression. We show
      here that clustering PSMA at LNCaP or PC3-PSMA cell membrane activates AKT and
      MAPK pathways thus promoting proliferation and survival. PSMA activity was
      dependent on the assembly of a macromolecular complex including filamin A, beta1
      integrin, p130CAS, c-Src and EGFR. Within this complex beta1 integrin became
      activated thereby inducing a c-Src-dependent EGFR phosphorylation at Y1086 and
      Y1173 EGF-independent residues. Silencing or blocking experiments with drugs
      demonstrated that all the complex components were required for full PSMA
      dependent promotion of cell growth and/or survival in 3D culture, but that
      p130CAS and EGFR exerted a major role. All PSMA complex components were found
      assembled in multiple samples of two high-grade prostate carcinomas and
      associated with EGFR phosphorylation at Y1086. The expression of p130CAS and
      pEGFRY1086 was thus analysed by tissue micro array in 16 castration-resistant
      prostate carcinomas selected from 309 carcinomas and stratified from GS 3+4 to GS
      5+5. Patients with Gleason Score <=5 resulted negative whereas those with GS>=5
      expressed p130CAS and pEGFRY1086 in 75% and 60% of the cases,
      respectively.Collectively, our results demonstrate for the first time that PSMA
      recruits a functionally active complex which is present in high-grade patients.
      In addition, two components of this complex, p130CAS and the novel pEGFRY1086,
      correlate with progression in castration-resistant patients and could be
      therefore useful in therapeutic or surveillance strategies of these patients.

PMID- 27713117
TI  - New combined microRNA and protein plasmatic biomarker panel for pancreatic
      cancer.
AB  - INTRODUCTION: Lack of diagnostic makers results in loss of operation opportunity
      in that most patients are diagnosed at the late stage. Pancreatic cancer (PC) has
      been regarded as a fatal disease with a 5-year survival rate below 10%.
      Therefore, the development of diagnostic biomarkers for PC is in urgent need to
      control the mortality of the disease. MATERIALS AND METHODS: This is a case
      control study including 640 plasma samples from healthy controls (HC), patients
      with benign pancreatic diseases (BPD), patients with PC; and patients with other
      gastrointestinal (GI) cancers. Eight biomarker candidates, including miR-20a, miR
      21, miR-25, miR-155, miR-196a, miR-210, Macrophage Inhibitory Cytokine-1(MIC-1)
      and CA19-9, were evaluated to establish two diagnostic indexes in this study.
      RESULTS: The plasma level of the six miRNAs and MIC-1, CA19-9 were elevated in PC
      patients compared with those of healthy controls (P<0.001). Among them, miR-20a,
      miR-21, miR-25, MIC-1 and CA19-9 could distinguish PC patients from those with
      other GI cancers or BPD. With multivariable logistic regression, we established
      two specific indexes for diagnosis of PC(Index1 contains miR-21, MIC-1 and CA19
      9; Index2 contains miR-25, MIC-1 and CA19-9). In a randomized setting of 260 HC,
      168 PC, 132 other GI cancers and 80 BPD patients, both indexes performed not only
      better sensitivity for PC but also better specificity to distinguish PC from
      other GI cancers than CA19-9 and individual biomarkers. CONCLUSIONS: These
      results indicated that combination of biomarkers as a panel could improve
      diagnostic values compared with using a single marker. Such panels as illustrated
      in this study could provide novel plasmatic biomarker for PC diagnosis.

PMID- 27713118
TI  - Exploring the interactions of the RAS family in the human protein network and
      their potential implications in RAS-directed therapies.
AB  - RAS proteins are the founding members of the RAS superfamily of GTPases. They are
      involved in key signaling pathways regulating essential cellular functions such
      as cell growth and differentiation. As a result, their deregulation by
      inactivating mutations often results in aberrant cell proliferation and cancer.
      With the exception of the relatively well-known KRAS, HRAS and NRAS proteins,
      little is known about how the interactions of the other RAS human paralogs affect
      cancer evolution and response to treatment. In this study we performed a
      comprehensive analysis of the relationship between the phylogeny of RAS proteins
      and their location in the protein interaction network. This analysis was
      integrated with the structural analysis of conserved positions in available 3D
      structures of RAS complexes. Our results show that many RAS proteins with
      divergent sequences are found close together in the human interactome. We found
      specific conserved amino acid positions in this group that map to the binding
      sites of RAS with many of their signaling effectors, suggesting that these pairs
      could share interacting partners. These results underscore the potential
      relevance of cross-talking in the RAS signaling network, which should be taken
      into account when considering the inhibitory activity of drugs targeting specific
      RAS oncoproteins. This study broadens our understanding of the human RAS
      signaling network and stresses the importance of considering its potential cross
      talk in future therapies.

PMID- 27713119
TI  - Concurrent MEK targeted therapy prevents MAPK pathway reactivation during
      BRAFV600E targeted inhibition in a novel syngeneic murine glioma model.
AB  - Inhibitors of BRAFV600E kinase are currently under investigations in preclinical
      and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical
      response to such individualized therapy in the majority of patients whereas in
      some patients tumors continue to grow despite treatment. To study resistance
      mechanisms, which include feedback activation of mitogen-activated protein kinase
      (MAPK) signaling in melanoma, we developed a luciferase-modified cell line
      (2341luc) from a BrafV600E mutant and Cdkn2a- deficient murine high-grade glioma,
      and analyzed its molecular responses to BRAFV600E- and MAPK kinase (MEK)-targeted
      inhibition. Immunocompetent, syngeneic FVB/N mice with intracranial grafts of
      2341luc were tested for effects of BRAFV600E and MEK inhibitor treatments, with
      bioluminescence imaging up to 14-days after start of treatment and survival
      analysis as primary indicators of inhibitor activity. Intracranial injected tumor
      cells consistently generated high-grade glioma-like tumors in syngeneic mice.
      Intraperitoneal daily delivery of BRAFV600E inhibitor dabrafenib only transiently
      suppressed MAPK signaling, and rather increased Akt signaling and failed to
      extend survival for mice with intracranial 2341luc tumor. MEK inhibitor
      trametinib delivered by oral gavage daily suppressed MAPK pathway more
      effectively and had a more durable anti-growth effect than dabrafenib as well as
      a significant survival benefit. Compared with either agent alone, combined
      BRAFV600E and MEK inhibitor treatment was more effective in reducing tumor growth
      and extending animal subject survival, as corresponding to sustained MAPK pathway
      inhibition. Results derived from the 2341luc engraftment model application have
      clinical implications for the management of BRAFV600E glioma.

PMID- 27713120
TI  - Automated analysis of acute myeloid leukemia minimal residual disease using a
      support vector machine.
AB  - We investigated the ability of support vector machines (SVM) to analyze minimal
      residual disease (MRD) in flow cytometry data from patients with acute myeloid
      leukemia (AML) automatically, objectively and standardly. The initial disease
      data and MRD review data in the form of 159 flow cytometry standard 3.0 files
      from 36 CD7-positive AML patients in whom MRD was detected more than once were
      exported. SVM was used for training with setting the initial disease data to 1 as
      the flag and setting 15 healthy persons to set 0 as the flag. Based on the two
      training groups, parameters were optimized, and a predictive model was built to
      analyze MRD data from each patient. The automated analysis results from the SVM
      model were compared to those obtained through conventional analysis to determine
      reliability. Automated analysis results based on the model did not differ from
      and were correlated with results obtained through conventional analysis
      (correlation coefficient c = 0.986, P > 0.05). Thus the SVM model could
      potentially be used to analyze flow cytometry-based AML MRD data automatically,
      objectively, and in a standardized manner.

PMID- 27713121
TI  - MicroRNA-130a alleviates human coronary artery endothelial cell injury and
      inflammatory responses by targeting PTEN via activating PI3K/Akt/eNOS signaling
      pathway.
AB  - Our study aims to investigate the roles of microRNA-130a (miR-130a) in human
      coronary artery endothelial cells (HCAECs) injury and inflammatory responses by
      targeting PTEN through the PI3K/Akt/eNOS signaling pathway. HCAECs were treated
      with 1.0 mmol/L homocysteine (HCY) and assigned into eight groups: the blank
      group, the negative control (NC) group, the miR-130a mimics group, the miR-130a
      inhibitors group, the si-PTEN group, the Wortmannin group, the miR-130a
      inhibitors + si-PTEN group and the miR-130a mimics + Wortmannin group. Luciferase
      reporter gene assay was used to validate the relationship between miR-130a and
      PTEN. The expressions of miR-130a, PTEN and PI3K/Akt/eNOS signaling pathway
      related proteins were detected by qRT-PCR assay and Western blotting. MTT assay
      and Hoechst 33258 staining were adopted to testify cell growth and apoptosis. The
      NO kit assay was used to detect the NO release. ELISA was conducted to measure
      serum cytokine levels. Luciferase reporter gene assay confirmed the target
      relationship between miR-130a and PTEN. Compared with the blank and NC groups,
      the miR-130a mimics and si-PTEN groups showed significant increases in the
      expressions of PI3K/Akt/eNOS signaling pathway-related proteins, cell viability
      and the NO release, while serum cytokine levels and cell apoptosis were
      decreased; by contrast, an opposite trend was observed in miR-130a inhibitors and
      Wortmannin groups. However, no significant difference was found in the miR-130a
      inhibitors + si-PTEN and miR-130a mimics + Wortmannin groups when compared with
      the blank group. These results indicate that miR-130a could alleviate HCAECs
      injury and inflammatory responses by down-regulating PTEN and activating
      PI3K/Akt/eNOS signaling pathway.

PMID- 27713122
TI  - Depletion of pro-oncogenic RUNX2 enhances gemcitabine (GEM) sensitivity of p53
      mutated pancreatic cancer Panc-1 cells through the induction of pro-apoptotic
      TAp63.
AB  - Recently, we have described that siRNA-mediated silencing of runt-related
      transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM)
      sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the
      augmentation of p53 family TAp63-dependent cell death pathway. In this
      manuscript, we have extended our study to p53-mutated human pancreatic cancer
      Panc-1 cells. According to our present results, knockdown of mutant p53 alone had
      a marginal effect on GEM-mediated cell death of Panc-1 cells. We then sought to
      deplete RUNX2 using siRNA in Panc-1 cells and examined its effect on GEM
      sensitivity. Under our experimental conditions, RUNX2 knockdown caused a
      significant enhancement of GEM sensitivity of Panc-1 cells. Notably, GEM-mediated
      induction of TAp63 but not of TAp73 was further stimulated in RUNX2-depleted Panc
      1 cells, indicating that, like AsPC-1 cells, TAp63 might play a pivotal role in
      the regulation of GEM sensitivity of Panc-1 cells. Consistent with this notion,
      forced expression of TAp63alpha in Panc-1 cells promoted cell cycle arrest and/or
      cell death, and massively increased luciferase activities driven by TAp63-target
      gene promoters such as p21WAF1 and NOXA. In addition, immunoprecipitation
      experiments indicated that RUNX2 forms a complex with TAp63 in Panc-1 cells.
      Taken together, our current observations strongly suggest that depletion of RUNX2
      enhances the cytotoxic effect of GEM on p53-mutated Panc-1 cells through the
      stimulation of TAp63-dependent cell death pathway even in the presence of a large
      amount of pro-oncogenic mutant p53, and might provide an attractive strategy to
      treat pancreatic cancer patients with p53 mutations.

PMID- 27713123
TI  - Abnormal amphiregulin expression correlates with gastric cancer prognosis.
AB  - Gastric cancer (GC) is a global health issue with a high mortality rate. Early
      diagnosis and tracking of GC is a challenge due to a lack of reliable tools.
      Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family that
      activates growth signaling upon binding of EGF receptors. Elevated AREG
      expression is associated with various pathological conditions, including cancer.
      Here, we investigated whether increased AREG expression is a disease indicator
      and/or prognostic biomarker for GC. We used tissue microarray and quantitative
      real-time polymerase chain reaction to assess AREG expression in clinical tissue
      specimens at various stages of GC and a conducted bioinformatics analysis to
      evaluate the value of AREG over-expression as a GC biomarker. We found that both
      mRNA and protein expression of AREG were increased in the tissues of GC patients
      when compared to tissues from non-cancer patients or normal tissues. High
      expression of AREG was also associated with GC clinicopathological
      characteristics and poor survival. Thus, over-expression of AREG could serve as a
      novel GC biomarker, and active surveillance of its expression could be a novel
      approach to GC diagnosis and monitoring.

PMID- 27713125
TI  - Secondary malignancies after partial versus whole breast irradiation: a
      systematic review and meta-analysis.
AB  - Secondary malignancies are a common complication for patients receiving
      radiotherapy. Here, we compared rates of secondary malignancies after partial
      breast irradiation (PBI) and whole breast irradiation (WBI). The MEDLINE, EMBASE,
      and the Cochrane Library databases were systematically searched to identify
      relevant randomized clinical trials comparing PBI with WBI in breast cancer
      patients treated with breast-conserving therapy. Four studies including 2,185
      patients were selected. Compared to WBI, the pooled odds ratios (OR) for
      contralateral breast cancer were 0.86 (95% confidence interval (CI) 0.31-2.42; p
      = 0.78) after 5 years and 1.15 (95% CI 0.43-3.09; p = 0.78) after 10 years for
      PBI. The pooled ORs for secondary non-breast cancer were 0.91 (95% CI 0.49-1.67;
      p = 0.77) after 5 years and 1.20 (95% CI 0.39-3.66; p = 0.75) after 10 years for
      PBI compared to WBI. These results demonstrate that the risk of secondary
      malignancies is similar for PBI and WBI after breast-conserving radiotherapy.

PMID- 27713124
TI  - Neutrophilia in locally advanced cervical cancer: A novel biomarker for image
      guided adaptive brachytherapy?
AB  - OBJECTIVE: To study the prognostic value of leucocyte disorders in a prospective
      cohort of cervical cancer patients receiving definitive chemoradiation plus image
      guided adaptive brachytherapy (IGABT). RESULTS: 113 patients were identified. All
      patients received a pelvic irradiation concomitant with chemotherapy, extended to
      the para-aortic area in 13 patients with IVB disease. Neutrophilia and
      leukocytosis were significant univariate prognostic factors for poorer local
      failure-free survival (p = 0.000 and p = 0.002, respectively), associated with
      tumor size, high-risk clinical target volume (HR-CTV) and anemia. No effect was
      shown for distant metastases but leukocytosis and neutrophila were both poor
      prognostic factors for in-field relapses (p = 0.003 and p < 0.001). In
      multivariate analysis, HR-CTV volume (p = 0.026) and neutrophils count >
      7,500/MUl (p = 0.018) were independent factors for poorer survival without local
      failure, with hazard ratio (HR) of 3.1. MATERIALS AND METHODS: We examined
      patients treated in our Institution between April 2009 and July 2015 by
      concurrent chemoradiation (45 Gy in 25 fractions +/- lymph node boosts) followed
      by a magnetic resonance imaging (MRI)-guided adaptive pulse-dose rate
      brachytherapy (15 Gy to the intermediate-risk clinical target volume). The
      prognostic value of pretreatment leucocyte disorders was examined. Leukocytosis
      and neutrophilia were defined as a leukocyte count or a neutrophils count
      exceeding 10,000 and 7,500/MUl, respectively. CONCLUSIONS: Neutrophilia is a
      significant prognostic factor for local relapse in locally advanced cervical
      cancer treated with MRI-based IGABT. This biomarker could help identifying
      patients with higher risk of local relapse and requiring dose escalation.

PMID- 27713126
TI  - 18beta-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p
      Wnt-1 signaling.
AB  - 18beta-glycyrrhetinic acid (GRA) exerts anti-tumor effects on various types of
      cancer. In the present study, we found that GRA attenuated the severity of
      gastritis and suppressed gastric tumorigenesis in transgenic mice. We also
      discovered that miR-149-3p was downregulated in gastric cancer tissues and cell
      lines as compared to normal gastric tissues and epithelial cells, but was
      upregulated by GRA. miR-149-3p expression also correlated negatively with
      lymphnode metastasis. Our functional assays showed that miR-149-3p overexpression
      inhibited cell proliferation and cell cycle progression while inducing apoptosis,
      while inhibition of miR-149-3p had the opposite effects. In addition, we
      identified Wnt-1 as a direct target of miR-149-3p. These data suggest that GRA
      inhibits the initiation and progression of gastric tumors by ameliorating the
      inflammatory microenvironment through downregulation of COX-2 expression and by
      inhibiting Wnt-1 expression through the upregulation of tumor suppressor miR-149
      3p. GRA may thus have the potential to serve as a useful therapeutic agent for
      the prevention and treatment of gastric cancer.

PMID- 27713127
TI  - Induction treatments for acute promyelocytic leukemia: a network meta-analysis.
AB  - BACKGROUND: 9 treatments for acute promyelocytic leukemia (APL) have been
      compared in many randomized controlled trials (RCT). The conclusions have been
      inconsistent and the purpose of this study is to conduct a network meta-analysis.
      RESULTS: Rankings of event-free survival are ATRA+RIF (81.2%), ATRA+ATO (69.6%),
      ATO (50.6%). Rankings of complete remission are ATRA+RIF (79.3%), ATRA+ATO
      (64.8%), RIF (60.3%), ATO (55.9%). Rankings of avoiding differentiation syndromes
      are CT (84.3%), ATO (80.3%), RIF (71.6%), ATRA+RIF (49%), ATRA+ATO (40.8%).
      METHODS: A total of 1,666 patients from 12 RCTs were enrolled. The frequentist
      method was used. Relative risks with 95% confidence intervals were calculated. We
      produced a network plot, a contribution plot, and a forest plot predictive
      intervals. The inconsistency factor, the surface under the cumulative ranking
      curve and the publication bias were evaluated. CONCLUSIONS: ATRA+ATO is eligible
      to be the first-line treatment for APL. ATRA+RIF is a prospective alternative to
      the first-line treatment. RIF or ATO should be reconsidered as another option for
      de novo APL.

PMID- 27713128
TI  - Spc24 is required for meiotic kinetochore-microtubule attachment and production
      of euploid eggs.
AB  - Mammalian oocytes are particularly error prone in chromosome segregation during
      two successive meiotic divisions. The proper kinetochore-microtubule attachment
      is a prerequisite for faithful chromosome segregation during meiosis. Here, we
      report that Spc24 localizes at the kinetochores during mouse oocyte meiosis.
      Depletion of Spc24 using specific siRNA injection caused defective kinetochore
      microtubule attachments and chromosome misalignment, and accelerated the first
      meiosis by abrogating the kinetochore recruitment of spindle assembly checkpoint
      protein Mad2, leading to a high incidence of aneuploidy. Thus, Spc24 plays an
      important role in genomic stability maintenance during oocyte meiotic maturation.

PMID- 27713130
TI  - Increased gene expression noise in human cancers is correlated with low p53 and
      immune activities as well as late stage cancer.
AB  - Gene expression in metazoans is delicately organized. As genetic information
      transmits from DNA to RNA and protein, expression noise is inevitably generated.
      Recent studies begin to unveil the mechanisms of gene expression noise control,
      but the changes of gene expression precision in pathologic conditions like
      cancers are unknown. Here we analyzed the transcriptomic data of human breast,
      liver, lung and colon cancers, and found that the expression noise of more than
      74.9% genes was increased in cancer tissues as compared to adjacent normal
      tissues. This suggested that gene expression precision controlling collapsed
      during cancer development. A set of 269 genes with noise increased more than 2
      fold were identified across different cancer types. These genes were involved in
      cell adhesion, catalytic and metabolic functions, implying the vulnerability of
      deregulation of these processes in cancers. We also observed a tendency of
      increased expression noise in patients with low p53 and immune activity in
      breast, liver and lung caners but not in colon cancers, which indicated the
      contributions of p53 signaling and host immune surveillance to gene expression
      noise in cancers. Moreover, more than 53.7% genes had increased noise in patients
      with late stage than early stage cancers, suggesting that gene expression
      precision was associated with cancer outcome. Together, these results provided
      genomic scale explorations of gene expression noise control in human cancers.

PMID- 27713129
TI  - New strategy to rescue the inhibition of osteogenesis of human bone marrow
      derived mesenchymal stem cells under oxidative stress: combination of vitamin C
      and graphene foams.
AB  - To rescue the oxidative stress induced inhibition of osteogenesis, vitamin C (VC)
      was chemically modified onto three-dimensional graphene foams (3D GFs), then
      their regulation on osteogenesis of human bone marrow-derived mesenchymal stem
      cells (BM-MSCs) was studied. Combined action of VC + GF significantly decreased
      H2O2-induced oxidative stress, and rescued H2O2-inhibited cell viability,
      differentiation and osteogenesis of BM-MSCs in vitro. Further studies revealed
      that Wnt pathway may be involved in this protection of osteogenesis. Furthermore,
      an in vivo mouse model of BM-MSCs transplantation showed that VC + GF remarkably
      rescued oxidative stress inhibited calcium content and bone formation. The
      combination of VC and GF exhibited more pronounced protective effects against
      oxidative stress induced inhibition of osteogenesis, compared to monotherapy of
      VC or GF. Our study proposed a new strategy in stem cell-based therapies for
      treating bone diseases.

PMID- 27713131
TI  - Discovery of cell surface vimentin targeting mAb for direct disruption of GBM
      tumor initiating cells.
AB  - Intracellular vimentin overexpression has been associated with epithelial
      mesenchymal transition, metastasis, invasion, and proliferation, but cell surface
      vimentin (CSV) is less understood. Furthermore, it remains unknown whether CSV
      can serve as a therapeutic target in CSV-expressing tumor cells. We found that
      CSV was present on glioblastoma multiforme (GBM) cancer stem cells and that CSV
      expression was associated with spheroid formation in those cells. A newly
      developed monoclonal antibody against CSV, 86C, specifically and significantly
      induced apoptosis and inhibited spheroid formation in GBM cells in vitro. The
      addition of 86C to GBM cells in vitro also led to rapid internalization of
      vimentin and decreased GBM cell viability. These findings were associated with an
      increase in caspase-3 activity, indicating activation of apoptosis. Finally,
      treatment with 86C inhibited GBM progression in vivo. In conclusion, CSV
      expressing GBM cells have properties of tumor initiating cells, and targeting CSV
      with the monoclonal antibody 86C is a promising approach in the treatment of GBM.

PMID- 27713132
TI  - Highly elevated serum lactate dehydrogenase is associated with central nervous
      system relapse in patients with diffuse large B-cell lymphoma: Results of a
      multicenter prospective cohort study.
AB  - Central nervous system involvement remains a challenging issue in the treatment
      of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort
      study with newly diagnosed diffuse large B-cell lymphoma patients receiving
      rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify
      incidence and risk factors for central nervous system involvement. Among 595
      patients, 279 patients received pre-treatment central nervous system evaluation,
      and 14 patients had central nervous system involvement at diagnosis (2.3% out of
      entire patients and 5.0% out of the 279 patients). For those patients, median
      follow-up duration was 38.2 months and some of them achieved long-term survival.
      Out of 581 patients who did not have central nervous system involvement at
      diagnosis, 26 patients underwent secondary central nervous system relapse with a
      median follow-up of 35 months, and the median time to central nervous system
      involvement was 10.4 months (range: 3.4-29.2). Serum lactate dehydrogenase > *3
      upper limit of normal range, the Eastern Cooperative Oncology Group performance
      status >= 2, and involvement of sinonasal tract or testis, were independent risk
      factors for central nervous system relapse in multivariate analysis. Our study
      suggests that enhanced stratification of serum lactate dehydrogenase according to
      the National Comprehensive Cancer Network-International Prognostic Index may
      contribute to better prediction for central nervous system relapse in patients
      with diffuse large B-cell lymphoma. This trial was registered at
      clinicaltrials.gov identifier: 01202448.

PMID- 27713133
TI  - Long non-coding RNAs in anti-cancer drug resistance.
AB  - Chemotherapy is one of the basic treatments for cancers; however, drug resistance
      is mainly responsible for the failure of clinical treatment. The mechanism of
      drug resistance is complicated because of interaction among various factors
      including drug efflux, DNA damage repair, apoptosis and targets mutation. Long
      non-coding RNAs (lncRNAs) have been a focus of research in the field of
      bioscience, and the latest studies have revealed that lncRNAs play essential
      roles in drug resistance in breast cancer, gastric cancer and lung cancer, et al.
      Dysregulation of multiple targets and pathways by lncRNAs results in the
      occurrence of chemoresistance. In this review, we will discuss the mechanisms
      underlying lncRNA-mediated resistance to chemotherapy and the therapeutic
      potential of lncRNAs in future cancer treatment.

PMID- 27713135
TI  - Recombinant heat shock protein 70 functional peptide and alpha-fetoprotein
      epitope peptide vaccine elicits specific anti-tumor immunity.
AB  - Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves
      as a target for immunotherapy. However, current treatments targeting AFP are not
      reproducible and do not provide complete protection against cancer. This issue
      may be solved by developing novel therapeutic vaccines with enhanced
      immunogenicity that could effectively target AFP-expressing tumors. In this
      study, we report construction of a therapeutic peptide vaccine by linking heat
      shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70
      P/AFP-P. This novel peptide was administered into BALB/c mice to observe the
      effects. Quantification of AFP-specific CD8 + T cells that secrete IFN-gamma in
      these mice via ELISPOT revealed the synergistic effects of HSP70-P/AFP-P with
      increased numbers of AFP-specific CD8 + T cells. Similarly, ELISA analysis showed
      increased granzyme B and perforin released by natural killer cells. Moreover, in
      vitro cytotoxic T-lymphocyte assays and in vivo tumor preventive experiments
      clearly showed the higher antitumor effects of HSP70-P/AFP-P against AFP
      expressing tumors. These results show that treatment of BALB/c mice with HSP70
      P/AFP-P induced stronger T-cells responses and improved protective immunity. Our
      data suggest that HSP70-P/AFP-P may be used as a therapeutic approach in the
      treatment of AFP-expressing cancers.

PMID- 27713134
TI  - A three ion channel genes-based signature predicts prognosis of primary
      glioblastoma patients and reveals a chemotherapy sensitive subtype.
AB  - Increasing evidence suggests that ion channels not only regulate electric
      signaling in excitable cells but also play important roles in the development of
      brain tumor. However, the roles of ion channels in glioma remain controversial.
      In the present study, we systematically analyzed the expression patterns of ion
      channel genes in a cohort of Chinese patients with glioma using RNAseq expression
      profiling. First, a molecular signature comprising three ion channel genes
      (KCNN4, KCNB1 and KCNJ10) was identified using Univariate Cox regression and two
      tailed student's t test conducted in overall survival (OS) and gene expression.
      We assigned a risk score based on three ion channel genes to each primary
      Glioblastoma multiforme (pGBM) patient. We demonstrated that pGBM patients who
      had a high risk of unfavorable outcome were sensitive to chemotherapy. Next, we
      screened the three ion genes-based signature in different molecular glioma
      subtypes. The signature showed a Mesenchymal subtype and wild-type IDH1
      preference. Gene ontology (GO) analysis for the functional annotation of the
      signature showed that patients with high-risk scores tended to exhibit the
      increased expression of proteins associated with apoptosis, immune response, cell
      adhesion and motion and vasculature development. Gene Set Enrichment Analysis
      (GSEA) results showed that pathways associated with negative regulation of
      programmed cell death, cell proliferation and locomotory behavior were highly
      expressed in the high-risk group. These results suggest that ion channel gene
      expression could improve the subtype classification in gliomas at the molecular
      level. The findings in the present study have been validated in two independent
      cohorts.

PMID- 27713137
TI  - A long noncoding RNA positively regulates CD56 in human natural killer cells.
AB  - Natural killer (NK) cells are innate immune lymphocytes that play critical roles
      in host defense against viral infection and surveillance against malignant
      transformation. Long noncoding RNAs (lncRNAs) are important immune system
      regulators. Here, we analyzed human primary lymphocyte lncRNA expression profiles
      to identify NK-lncRNA signatures. We detected numerous novel NK-specific lncRNAs
      with potential roles in regulating human NK cell differentiation and function.
      Expression of lnc-CD56, an NK-specific lncRNA, was positively correlated with
      that of CD56, a classical human NK cell surface marker. We showed that lnc-CD56
      may function as a positive regulator of CD56 in primary human NK cells and
      differentiated NK cells from human CD34+ hematopoietic progenitor cells. Our data
      provide an annotated human NK cell lncRNA expression catalog and demonstrate a
      key role for lncRNAs in NK cell biology.

PMID- 27713138
TI  - Transgenic and gene knockout mice in gastric cancer research.
AB  - Mouse models are useful tool for carcinogenic study. They will greatly enrich the
      understanding of pathogenesis and molecular mechanisms for gastric cancer.
      However, only few of mice could develop gastric cancer spontaneously. With the
      development and improvement of gene transfer technology, investigators created a
      variety of transgenic and knockout/knockin mouse models of gastric cancer, such
      as INS-GAS mice and gastrin knockout mice. Combined with helicobacter infection
      and carcinogens treatment, these transgenic/knockout/knockin mice developed
      precancerous or cancerous lesions, which are proper for gene function study or
      experimental therapy. Here we review the progression of genetically engineered
      mouse models on gastric cancer research, and emphasize the effects of chemical
      carcinogens or infectious factors on carcinogenesis of genetically modified
      mouse. We also emphasize the histological examination on mouse stomach. We expect
      to provide researchers with some inspirations on this field.

PMID- 27713139
TI  - Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis.
AB  - Increasing evidences indicate that the abnormal DNA methylation is involved in
      the pathogenesis of psoriasis. A number of SNPs in HLA-DRB1 have been found being
      associated with the risk of psoriasis, however it is unclear that metylation
      status within HLA-DRB1 in psoriasis. Here, DNA and RNA were obtained from
      epidermis of 56 patients with plaque psoriasis and 28 healthy volunteers served
      as the control group. For the first time, we discovered mean methylation rate for
      HLA-DRB1 is 52.2%, 64.3% and 68.1% in epidermis from psoriatic lesions, psoriatic
      non-lesions and healthy controls, respectively. HLA-DRB1 methylation in psoriatic
      lesions is significantly lower than in psoriatic non-lesions (t = 13.077, p <
      0.001). However, there is no significant difference for HLA-DRB1 methylation
      between in psoriatic non-lesions and in healthy controls (t = 1.046, p = 0.299).
      HLA-DRB1 methylation in psoriatic lesions is negatively correlated to PASI score
      (r = -0.431, p = 0.001). HLA-DRB1 methylation in psoriatic lesions of the
      patients with onset age<=18 years is significantly lower than the other patients
      (t = 3.968, p < 0.001). Meanwhile, HLA-DRB1 mRNA expression is significantly
      increased in psoriatic lesions comparing to psoriatic non-lesions (t = 12.119, p
      < 0.001). There are no significant difference for HLA-DRB1 mRNA expression
      between in psoriatic non-lesions and in healthy controls (t = 1.172, p = 0,245).
      Moreover, HLA-DRB1 mRNA expression is negatively associated with HLA-DRB1
      methylation in psoriatic lesions (r = 0.932, p < 0.001). In conclusions, our
      results showed hypomethylation of HLA-DRB1 is associated with HLA-DRB1 mRNA
      expression and severity of the disease, indicating that hypomethylation of HLA
      DRB1 may play roles in the pathogenesis of psoriasis.

PMID- 27713136
TI  - The role of extracellular vesicles in mediating progression, metastasis and
      potential treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a major cause of cancer-related death
      worldwide. As vectors for intercellular information exchange, the potential role
      of extracellular vesicles (EVs) in HCC formation, progression and therapy has
      been widely investigated. In this review, we explore the current status of the
      researches in this field. Altogether there is undeniable evidence that EVs play a
      crucial role in HCC development, metastasis. Moreover, EVs have shown great
      potential as drug delivery systems (DDSs) for the treatment of HCC. Exosomal
      miRNAs derived from HCC cells can enhance transformed cell growth in recipient
      cells by modulating the expression of transforming growth factor-beta activated
      kinase-1(TAK1) and downstream signaling molecules. Furthermore, vacuolar protein
      sortin 4 homolog A(VPS4A) and insulin-like growth factor(IGF)-1 regulate exosome
      mediated miRNAs transfer. Immune cells- derived EVs containing integrin
      alphaMbeta2 or CD147 may facilitate HCC metastasis. In addition, EVs-mediated
      shuttle of long non-coding RNAs (lncRNAs), specifically linc- VLDLR and linc-ROR
      promote chemoresistance of malignant cells. Heat shock proteins (HSPs)-harboring
      exosomes derived from HCC tumor cells increase the antitumor effect of natural
      killer (NK) cells, thus enhancing HCC immunotherapy. Indeed, inhibition of HCC
      tumor growth has been associated with tumor cell-derived exosomes (TEX)-pulsed
      dentritic cells (DCs). Exosomes are also essential in liver metastasis during
      colorectal carcinoma (CRC) and pancreatic ductal adenocarcinomas (PDAC).
      Therefore, as nucleic acid and drug delivery vehicles, EVs show a tremendous
      potential for effective treatment against HCC.

PMID- 27713140
TI  - Neuroprotective effects of CD4+CD25+Foxp3+ regulatory T cells in a 3xTg-AD
      Alzheimer's disease model.
AB  - Alzheimer's disease patients display neuropathological lesions, including the
      accumulation of amyloid-beta (Abeta) peptide and neurofibrillary tangles.
      Although the mechanisms causing the neurodegenerative process are largely
      unknown, increasing evidence highlights a critical role of immunity in the
      pathogenesis of Alzheimer's disease. In the present study, we investigated the
      role of regulatory T cells (Tregs) on Alzheimer's disease progression. First, we
      explored the effect of Tregs (CD4+CD25+ T cells) and Teffs (CD4+CD25- T cells) in
      an adoptive transfer model. Systemic transplantation of purified Tregs into 3xTg
      AD mice improved cognitive function and reduced deposition of Abeta plaques. In
      contrast, adoptive transfer of Teffs diminished behavioral function and cytokine
      production. Next, we transiently depleted Treg population using an anti-CD25
      antibody (PC61). Depletion of Tregs for four months resulted in a marked
      aggravation of the spatial learning deficits of six-month-old 3xTg-AD mice.
      Additionally, it resulted in decreasing glucose metabolism, as assessed by
      positron emission tomography (PET) with 18F-2 fluoro-2-deoxy-D-glucose ([F-18]
      FDG) neuroimaging. Importantly, the deposition of Abeta plaques and
      microglia/macrophage was increased in the hippocampal CA1 and CA3 regions of the
      Treg depleted 3xTg-AD compared to the vehicle-treated 3xTg-AD group. Our finding
      suggested that systemic Treg administration ameliorates disease progression and
      could be an effective Alzheimer's disease treatment.

PMID- 27713141
TI  - Fibroblast growth factor 23 dysregulates late sodium current and calcium
      homeostasis with enhanced arrhythmogenesis in pulmonary vein cardiomyocytes.
AB  - Fibroblast growth factor 23 (FGF23), elevated in chronic renal failure, increases
      atrial arrhythmogenesis and dysregulates calcium homeostasis. Late sodium
      currents (INa-Late) critically induces ectopic activity of pulmoanry vein (the
      most important atrial fibrillation trigger). This study was to investigate
      whether FGF23 activates the INa-Late leading to calcium dysregulation and
      increases PV arrhythmogenesis. Patch clamp, western blot, and confocal microscopy
      were used to evaluate the electrical activities, calcium homeostasis, and
      mitochondrial reactive oxygen species (ROS) in PV cardiomyocytes with or without
      FGF23 (0.1 or 1 ng/mL) incubation for 4~6 h. Compared to the control, FGF23 (1
      ng/mL, but not 0.1 ng/mL)-treated PV cardiomyocytes had a faster beating rate.
      FGF23 (1 ng/mL)-treated PV cardiomyocytes had larger INa-Late, calcium
      transients, and mitochondrial ROS than controls. However, ranolazine (an
      inhibitor of INa-Late) attenuated FGF23 (1 ng/mL)-increased beating rates,
      calcium transients and mitochondrial ROS. FGF23 (1 ng/mL)-treated PV
      cardiomyocytes exhibited larger phosphorylation of calcium/calmodulin-dependent
      protein kinase II (CaMKII). Chelerythrine chloride (an inhibitor of protein
      kinase C) decreased INa-Late in FGF23 (1 ng/mL)-treated PV cardiomyocytes.
      However, KN93 (a selective CaMKII blocker) decreased INa-Late in control and
      FGF23 (1 ng/mL)-treated PV cardiomyocytes to a similar extent. In conclusion,
      FGF23 increased PV arrhythmogenesis through sodium and calcium dysregulation by
      acting protein kinase C signaling.

PMID- 27713142
TI  - Novel circulating lipid measurements for current dyslipidemias in non-treated
      patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C.
AB  - Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9),
      apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol
      (sdLDL-C), have been recently recognized as circulating atherosclerosis-related
      lipid measurements. We aimed to elucidate their associations with current
      dyslipidemias, and identify their levels at increased risk to dyslipidemia. A
      total of 1,605 consecutive, non-treated patients undergoing
      diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and
      apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was
      measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C
      were associated with the current dyslipidemias classification (all p<0.001).
      PCSK9 significantly conferred prediction of both hypercholesterolemia and
      combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for
      hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0,
      71.5, and 86.4 MUg/ml, respectively; and sdLDL-C for hypertriglyceridemia,
      hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein
      (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for
      area under the receiver-operating characteristic curve). In a polytomous logistic
      model comparing increasing LDL-C categories, the interactions with high PCSK9,
      apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed
      elevated interaction with increased triglyceride categories, and only sdLDL-C
      showed interaction with decreased HDL cholesterol (HDL-C) categories.
      Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias
      were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with
      current dyslipidemias, and were predictive in the screening. The substantial
      discordances with current dyslipidemias might provide novel view in lipid
      management and further cardiovascular benefit.

PMID- 27713143
TI  - Signaling through hepatocyte vasopressin receptor 1 protects mouse liver from
      ischemia-reperfusion injury.
AB  - : Terlipressin has been used extensively in the management of certain
      complications associated with end-stage liver diseases (ESLDs). In our pilot
      study, terlipressin treatment showed beneficial effects on liver function in
      patients with decompensated cirrhosis, however whether it plays a role in liver
      ischemia-reperfusion injury (IRI) remains unknown. Using a mouse nonlethal
      hepatic IR model, we found terlipressin administration significantly ameliorated
      IR-induced liver apoptosis, necrosis and inflammation. Furthermore, despite its
      known effect on visceral vasoconstriction, hemodynamic evaluation of murine
      hepatic tissue after IR revealed no change of overall hepatic blood flow after
      terlipressin treatment. Further studies identified the upregulation of
      vasopressin receptor 1 (V1R) expression on hepatocytes upon IR. In isolated
      hepatocyte hypoxia/reoxygenation model, the active component of terlipressin,
      lysine vasopressin, conferred hepatocytes resistant to oxidative stress-induced
      apoptosis. Mechanistic studies revealed the V1R engagement activated the Wnt/beta
      catenin/FoxO3a/AKT pathway, which subsequently circumvented the proapoptotic
      events, thus ameliorated hepatocyte apoptosis. Furthermore, genetic knockdown of
      V1R expression in hepatocyte cell lines or blockade of this signaling pathway
      abrogated such protective effect. CONCLUSION: These data highlight the functional
      importance of the hepatocyte V1R/Wnt/beta-catenin/FoxO3a/AKT pathway in
      protecting liver from oxidative stress-induced injury.

PMID- 27713144
TI  - RGS6 is an essential tumor suppressor that prevents bladder carcinogenesis by
      promoting p53 activation and DNMT1 downregulation.
AB  - Urinary bladder cancer (UBC) is largely caused by exposure to toxic chemicals
      including those in cigarette smoke (i.e. BBN). An activating SNP in RGS6 is
      associated with a pronounced reduction in UBC risk, especially among smokers.
      However, the mechanism underlying this reduction remains unknown. Here we
      demonstrate that RGS6 is robustly expressed in human urothelium, where urothelial
      cell carcinoma originates, and is downregulated in human UBC. Utilizing RGS6-/-
      mice we interrogated a possible role for RGS6 as a tumor suppressor using the BBN
      induced bladder carcinogenesis model that closely recapitulates human disease. As
      in humans, RGS6 is robustly expressed in mouse urothelium. RGS6 loss dramatically
      accelerates BBN-induced bladder carcinogenesis, with RGS6-/- mice consistently
      displaying more advanced pathological lesions than RGS6+/+ mice. Furthermore, BBN
      treatment promotes urothelial RGS6 mRNA and protein downregulation. RGS6 loss
      impairs p53 activation and promotes aberrant accumulation of oncogenic protein
      DNMT1 in urothelium. Tumor suppressor RASSF1A, a DNMT1-regulated gene, is also
      silenced, likely via methylation of its promoter during BBN exposure. We
      hypothesize that this BBN-induced RGS6 loss represents a critical hit in UBC as
      it irrevocably impairs the anti-proliferative actions of the ATM/p53 and RASSF1A
      pathways. Consistent with these findings, RGS6-/- mice treated with CP-31398, a
      p53-stablizing agent, and/or 5-Aza, a DNMT1 inhibitor, are protected from BBN
      induced tumorigenesis. Together, our data identify RGS6 as a master tumor
      suppressor modulating two critical signaling pathways that are often dysregulated
      in UBC; therefore, RGS6 represents a potential novel biomarker for UBC
      diagnosis/prognosis and an appealing new target in its treatment.

PMID- 27713145
TI  - Glycodelin is a potential novel follow-up biomarker for malignant pleural
      mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a short
      survival time arising from the mesothelial cells of the pleura. Soluble
      mesothelin-related peptide (SMRP), osteopontin or EFEMP1 (Fibulin-3) are well
      described biomarkers for malignant mesothelioma with moderate sensitivity and
      specificity. In this study, we characterized the expression of glycodelin, a
      marker for risk pregnancy, in MPM by RNA and protein analyses and investigated
      its potential as a MPM biomarker. We were able to detect glycodelin in the serum
      of MPM patients. Compared to benign lung diseases, the serum levels were
      significant increased. Patients with high glycodelin serum levels revealed a
      worse overall survival. The glycodelin serum levels correlated with the tumor
      response to treatment. A comparison of SMRP and glycodelin serum measurement in a
      large patient cohort demonstrated that the detection of both soluble factors can
      increase the reliable diagnostic of MPM. Glycodelin was highly expressed in MPM
      tumors. Analyses of a tissue micro array indicated that the immunomodulatory form
      glycodelin A was expressed in MPM and correlated with the survival of the
      patients. Altogether, glycodelin seems to be a new potential biomarker for the
      aggressive malignant pleural mesothelioma.

PMID- 27713146
TI  - TGF-beta and NF-kappaB signaling pathway crosstalk potentiates corneal epithelial
      senescence through an RNA stress response.
AB  - The corneal epithelium plays important roles in the maintenance of corneal
      transparency for good vision, and acts as a protective barrier against foreign
      insults. Structural and functional changes with aging in the corneal epithelium
      have been documented. Here we found that transforming growth factor-beta (TGF
      beta) is highly expressed in the elderly donor corneal epithelium, as are
      senescence-associated genes, such as p16 and p21. In human corneal epithelial
      cell (HCEC) models, TGF-beta induces cellular senescence, characterized by
      increased SA-beta-gal positive cells and elevated expression of p16 and p21.
      Pharmacological inhibition of TGF-beta signaling alleviates TGF-beta-induced
      cellular senescence. In addition, we determined that senescence-associated
      inflammation was significantly aggravated in TGF-beta-induced cellular senescence
      by detecting the expression of interleukin-6 (IL-6), IL-8, and tumor necrosis
      factor alpha (TNFalpha). Both genetic and pharmacological approaches revealed
      that blocking nuclear factor-kappaB (NF-kappaB) signaling not only inhibited the
      production of inflammatory factors, but also rescued the senescent phenotype
      induced by TGF-beta in HCECs. Mechanistically, TGF-beta induced an atypical RNA
      stress responses, leading to accelerated mRNA degradation of IkappaBalpha, an
      inhibitor of NF-kappaB. Together, our data indicate that TGF-beta-driven NF
      kappaB activation contributes to corneal epithelial senescence via RNA metabolism
      and the inflammation blockade can attenuate TGF-beta-induced senescence.

PMID- 27713147
TI  - MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and
      recurrence-free survival in surgically resected CRC individuals.
AB  - Genetic variation within microRNA (miRNA) may result in its abnormal folding or
      aberrant expression, contributing to colorectal turmorigenesis and metastasis.
      However, the association of six polymorphisms (miR-608 rs4919510, miR-499a
      rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and
      pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response
      and survival remains unclear. A retrospective study was carried out to
      investigate the association in 1358 0-III stage resected CRC patients and 1079
      healthy controls using Sequenom's MassARRAY platform. The results showed that
      rs4919510 was significantly associated with a decreased susceptibility to CRC in
      co-dominant, allele and recessive genetic models, and the protective role of
      rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases;
      significant association between rs531564 and poor RFS was observed in cases
      undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant
      models; moreover, there was a positive association between rs7372209 and
      recurrence-free survival in stage II cases in co-dominant and over-dominant
      models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk
      genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes
      was examined in stage II cases, respectively. Our findings indicated that
      rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC,
      rs7372209 and rs531564 could decrease RFS in II stage individuals and resected
      CRC patients receiving adjuvant chemo-radiology.

PMID- 27713149
TI  - Human beta-defensin 3 contributes to the carcinogenesis of cervical cancer via
      activation of NF-kappaB signaling.
AB  - Human beta-defensin 3 (hBD3), an antimicrobial peptide (AMP) expressed in
      epithelium in response to various stimulations including human papillomavirus
      infection, has recently been found to be overexpressed in head and neck cancers
      and exhibit tumorigenic activities. However, the role of hBD3 in cervical cancer
      remains to be investigated. In this study, we showed by immunohistochemistry that
      hBD3 expression was elevated in cervical cancer samples of different stages
      versus the normal tissue, and was positively correlated with the progression of
      the disease. Overexpression of hBD3 in cervical cancer cell lines promoted cell
      proliferation by accelerating G1/S progression and enhanced cell migration and
      invasion in vitro. These oncogenic effects of hBD3 were associated with
      activation of NF-kappaB signaling. Using a mouse xenograft model, we further
      demonstrated that hBD3 overexpression promoted the growth of cervical cancer
      cells in vivo. Our results suggested that hBD3 is involved in the carcinogenesis
      and development of cervical cancer, and may serve as a biomarker or therapeutic
      target of this disease.

PMID- 27713148
TI  - A novel mechanism of action of HER2 targeted immunotherapy is explained by
      inhibition of NRF2 function in ovarian cancer cells.
AB  - Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic
      detoxification and crosstalk with growth promoting pathways. HER2 receptor
      tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled
      receptor activation and signaling. A combination of HER2 targeting monoclonal
      antibodies shows greater anticancer efficacy than the single targeting
      antibodies, however, its mechanism of action is largely unclear. Here we report
      novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2.HER2
      targeting by antibodies inhibited growth in association with persistent
      generation of reactive oxygen species (ROS), glutathione (GSH) depletion,
      reduction in NRF2 levels and inhibition of NRF2 function in ovarian cancer cell
      lines. The combination of antibodies produced more potent effects than single
      antibody alone; downregulated NRF2 substrates by repressing the Antioxidant
      Response (AR) pathway with concomitant transcriptional inhibition of NRF2. We
      showed the antibody combination produced increased methylation at the NRF2
      promoter consistent with repression of NRF2 antioxidant function, as HDAC and
      methylation inhibitors reversed such produced transcriptional effects. These
      findings demonstrate a novel mechanism and role for NRF2 in mediating the
      response of cancer cells to the combination of Trastuzumab and Pertuzumab and
      reinforce the importance of NRF2 in drug resistance and as a key anticancer
      target.

PMID- 27713150
TI  - Second-generation proteasome inhibitor carfilzomib sensitizes neuroblastoma cells
      to doxorubicin-induced apoptosis.
AB  - Neuroblastoma (NB), which accounts for about 15% of cancer-related mortality in
      children, is the most common extracranial malignant neoplasm in children.
      Elevated level of proteasome activity promotes cancer development and the
      inhibition of proteasome activity is a promising strategy for cancer treatment.
      Therefore, targeting proteasome by small molecule inhibitors may be a viable
      option for NB therapy. Here in this study, we show that a novel proteasome
      inhibitor Carfilzomib (CFZ) exerts anti-tumor effect on NB. CFZ caused decreased
      cell viability and attenuated colony formation ability of a subset of NB cell
      lines. CFZ induced cell apoptosis in NB cells. Moreover, CFZ enhanced the
      cytotoxic effect of doxorubicin (Dox) on NB cells and Dox-induced p38 and JNK
      phosphorylation. In addition, CFZ inhibited Dox-induced NF-kappaB activation by
      stabilizing the protein level of IkappaBalpha. Furthermore, CFZ induced apoptosis
      and augmented Dox-induced apoptosis in NB tumor cells in orthotopic xenograft
      mouse models. In summary, our study suggests that proteasome is a therapeutic
      target in NB and proteasome inhibition by CFZ is a potential therapeutic strategy
      for treating NB patients.

PMID- 27713151
TI  - Selinexor, a Selective Inhibitor of Nuclear Export (SINE) compound, acts through
      NF-kappaB deactivation and combines with proteasome inhibitors to synergistically
      induce tumor cell death.
AB  - The nuclear export protein, exportin-1 (XPO1/CRM1), is overexpressed in many
      cancers and correlates with poor prognosis. Selinexor, a first-in-class Selective
      Inhibitor of Nuclear Export (SINE) compound, binds covalently to XPO1 and blocks
      its function. Treatment of cancer cells with selinexor results in nuclear
      retention of major tumor suppressor proteins and cell cycle regulators, leading
      to growth arrest and apoptosis. Recently, we described the selection of SINE
      compound resistant cells and reported elevated expression of inflammation-related
      genes in these cells. Here, we demonstrated that NF-kappaB transcriptional
      activity is up-regulated in cells that are naturally resistant or have acquired
      resistance to SINE compounds. Resistance to SINE compounds was created by
      knockdown of the cellular NF-kappaB inhibitor, IkappaB-alpha. Combination
      treatment of selinexor with proteasome inhibitors decreased NF-kappaB activity,
      sensitized SINE compound resistant cells and showed synergistic cytotoxicity in
      vitro and in vivo. Furthermore, we showed that selinexor inhibited NF-kappaB
      activity by blocking phosphorylation of the IkappaB-alpha and the NF-kappaB p65
      subunits, protecting IkappaB-alpha from proteasome degradation and trapping
      IkappaB-alpha in the nucleus to suppress NF-kappaB activity. Therefore,
      combination treatment of selinexor with a proteasome inhibitor may be beneficial
      to patients with resistance to either single-agent.

PMID- 27713152
TI  - Detection of cellular senescence within human invasive breast carcinomas
      distinguishes different breast tumor subtypes.
AB  - Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by
      arresting cells at risk of malignant transformation. Nevertheless, numerous
      findings suggest that senescent cells may conversely promote tumor progression
      through the development of the senescence-associated secretome they produce. It
      is likely that the composition and the physiological consequences mediated by the
      senescence secretome are dependent on the oncogenes that trigger the senescence
      program. Breast cancer represents a heterogenous disease that can be divided into
      breast cancer subtypes due to different subsets of genetic and epigenetic
      abnormalities. As tumor initiation and progression of these breast cancer
      subtypes is triggered by diverse oncogenic stimuli, differences in the senescence
      secretomes within breast tumors might be responsible for tumor initiation,
      progression, metastasis and therapeutic response. Many studies have addressed the
      role of senescence as a barrier to tumor progression using murine xenograft
      models. However, few investigations have been performed to elucidate the degree
      to which senescent tumor cells are present within untreated human tumors, and if
      present, whether these senescent tumor cells may play a role in disease
      progression. In the present study we analysed the appearance of senescent cells
      within invasive breast cancers. Detection of cellular senescence by the use of
      SAbeta-galactosidase (SAbeta-gal) staining within invasive breast carcinoms from
      129 untreated patients revealed differences in the amount of SAbeta-gal+ tumor
      cells between breast cancer subtypes. The highest percentages of SAbeta-gal+
      tumor cells were found in HER2-positive and luminal A breast carcinomas whereas
      triple negative tumors showed either little or no positivity.

PMID- 27713153
TI  - CCND1 mutations increase protein stability and promote ibrutinib resistance in
      mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation, which
      leads to deregulated expression of the cell cycle regulatory protein cyclin D1
      (CCND1). Genomic studies of MCL have also identified recurrent mutations in the
      coding region of CCND1. However, the functional consequence of these mutations is
      not known. Here, we showed that, compared to wild type (WT), single E36K, Y44D or
      C47S CCND1 mutations increased CCND1 protein levels in MCL cell lines.
      Mechanistically, these mutations stabilized CCND1 protein through attenuation of
      threonine-286 phosphorylation, which is important for proteolysis through the
      ubiquitin-proteasome pathway. In addition, the mutant proteins preferentially
      localized to the nucleus. Interestingly, forced expression of WT or mutant CCND1
      increased resistance of MCL cell lines to ibrutinib, an FDA-approved Bruton
      tyrosine kinase inhibitor for MCL treatment. The Y44D mutant sustained the
      resistance to ibrutinib even at supraphysiologic concentrations (5-10 MUM).
      Furthermore, primary MCL tumors with CCND1 mutations also expressed stable CCND1
      protein and were resistant to ibrutinib. These findings uncover a new mechanism
      that is critical for the regulation of CCND1 protein levels, and is directly
      relevant to primary ibrutinib resistance in MCL.

PMID- 27713155
TI  - Chicken GHR natural antisense transcript regulates GHR mRNA in LMH cells.
AB  - Growth hormone receptor (GHR) played key roles in human and animal growth. Both
      human laron type dwarfism and sex linked dwarf chicken were caused by the
      mutation of GHR gene. In this study, we identified an endogenously expressed long
      non-coding natural antisense transcript, GHR-AS, which overlapped with the GHR
      mRNA (GHR-S) in a tail to tail manner. Spatial and temporal expression analyses
      indicated that GHR-AS were highly expressed in chicken liver and displayed
      ascending with the development of chicken from E10 to 3 w of age. Interfering GHR
      AS caused GHR-S decreasing, accompanied with increasing of the inactive gene
      indicator, H3K9me2, in the GHR-S promoter regions in LMH cells. RNase A
      experiment exhibited that GHR-AS and GHR-S can form double strand RNAs at the
      last exon of GHR gene in vivo and in vitro, which hinted they could act on each
      other via the region. In addition, the levels of GHR-S and GHR-AS can be affected
      by DNA methylation. Compared the normal chicken with the dwarfs, the negative
      correlation trends were showed between the GHR-S promoter methylation status and
      the GHR-AS levels. This is the first report of that GHR gene possessed natural
      antisense transcript and the results presented here further highlight the fine
      and complicated regulating mechanism of GHR gene in chicken development.

PMID- 27713154
TI  - NRF2 promotes breast cancer cell proliferation and metastasis by increasing
      RhoA/ROCK pathway signal transduction.
AB  - Nuclear factor erythroid 2-related factor (NRF2) is an important transcription
      factor in oxidative stress regulation. Overexpression of NRF2 is associated with
      human breast carcinogenesis, and increased NRF2 mRNA levels predict poor patient
      outcome for breast cancer. However, the mechanisms linking gain of NRF2
      expression and poor prognosis in breast cancer are still unclear. Here, we
      provide evidence that NRF2 deletion inhibits proliferation and metastasis of
      breast cancer cells by down-regulating RhoA. Restoration of RhoA in MCF7 and MDA
      MB-231 cells induced NRF2 knockdown-suppressed cell growth and metastasis in
      vitro, and NRF2 silencing suppressed stress fiber and focal adhesion formation
      leading to decreased cell migration and invasion. Mechanistic studies showed that
      NRF2 binds to the promoter region of estrogen-related receptor alpha (ERR1) and
      may function as a silencer. This may enhance RhoA protein stability and lead to
      RhoA overexpression in breast cancer cell. Our findings indicate that NRF2
      silencing-mediated reduction of RhoA expression contributes, at least in part, to
      the poor outcome of breast cancer patients with high NRF2 expression.

PMID- 27713156
TI  - Kindlin-2 interacts with beta-catenin and YB-1 to enhance EGFR transcription
      during glioma progression.
AB  - Kindlin-2 promotes carcinogenesis through regulation of cell-cell and cell
      extracellular matrix adhesion. However, the role of Kindlin-2 in glioma has not
      been elucidated. We investigated Kindlin-2 expression in 188 human glioma tissue
      samples. High Kindlin-2 expression was correlated with high pathological grade
      and a worse prognosis. Kindlin-2 promoted glioma cell motility and proliferation
      both in vitro and in vivo. Importantly, Kindlin-2 activated the EGFR pathway and
      increased EGFR mRNA levels. In addition to up-regulating Y-box binding protein-1
      (YB-1) and beta-catenin expression, Kindlin-2 formed a transcriptional complex
      with YB-1 and beta-catenin that bound to the EGFR promoter and enhanced
      transcription. The beta-catenin/YB-1/EGFR pathway was required for Kindlin-2
      mediated functions. Our data provide a better understanding of the mechanisms
      underlying glioma progression, and suggest that Kindlin-2 may be a biomarker and
      therapeutic target in glioma.

PMID- 27713158
TI  - Cancer cell-binding peptide fused Fc domain activates immune effector cells and
      blocks tumor growth.
AB  - Therapeutic strategies aiming at mobilizing immune effector cells to kill tumor
      cells independent of tumor mutational load and MHC expression status are expected
      to benefit cancer patients. Recently, we engineered various peptide-Fc fusion
      proteins for directing Fcg receptor-bearing immune cells toward tumor cells.
      Here, we investigated the immunostimulatory and anti-tumor effects of one of the
      engineered Fc fusion proteins (WN-Fc). In contrast to the Fc control, soluble WN
      Fc-1 fusion protein activated innate immune cells (e.g. monocytes, macrophages,
      dendritic cells, NK cells), resulting in cytokine production and surface display
      of the lytic granule marker CD107a on NK cells. An engineered Fc-fusion variant
      carrying two peptide sequences (WN-Fc-2) also activated immune cells and bound to
      various cancer cell types with high affinity, including the murine 4T1 breast
      carcinoma cells. When injected into 4T1 tumor-bearing BALB/c mice, both peptide
      Fc fusions accumulated in tumor tissues as compared to other organs such as the
      lungs. Moreover, treatment of 4T1 tumor-bearing BALB/c mice by means of two
      intravenous injections of the WN-Fc fusion proteins inhibited tumor growth with
      WN-Fc-2 being more effective than WN-Fc-1. Treatment resulted in tumor
      infiltration by T cells and NK cells. These new engineered WN-Fc fusion proteins
      may be a promising alternative to existing immunotherapies for cancer.

PMID- 27713157
TI  - Delayed reendothelialization with rapamycin is rescued by the addition of
      nicorandil in balloon-injured rat carotid arteries.
AB  - Rapamycin is an immunosuppressive agent that is added to drug eluting stents. It
      prevents restenosis, but it also impairs reendothelialization. Nicorandil is a
      hybrid agent with adenosine triphosphated (ATP)-sensitive K+ (KATP) channel
      opener and nitrate properties. It prevents oxidative stress and cell apoptosis
      induced by rapamycin in endothelial cells in vitro. However, whether nicorandil
      promotes reendothelialization after angioplasty delayed by rapamycin remains to
      be determined. Balloon injury model was established in SD rats. Nicorandil
      increased reendothelialization impaired by rapamycin, and it decreased xanthine
      oxidase (XO)-generated reactive oxygen species (ROS) induced by rapamycin. In
      addition, eNOS expression inhibited by rapamycin was increased by nicorandil in
      vivo. In vitro, rapamycin-impeded cardiac microvascular endothelial cells (CMECs)
      migration, proliferation and rapamycin-induced ROS production were reversed by
      nicorandil. Knockdown of XO partially inhibited rapamycin-induced ROS production
      and cell apoptosis in CMECs, and it promoted CMECs migration and proliferation
      suppressed by rapamycin. Knockdown of Akt partially prevents eNOS upregulation
      promoted by nicorandil. The beneficial effect of nicorandil is exhibited by
      inhibiting XO and up-regulating Akt pathway. Nicorandil combined with rapamycin
      in effect rescue the deficiencies of rapamycin alone in arterial healing after
      angioplasty.

PMID- 27713159
TI  - Lipopolysaccharide increases the release of VEGF-C that enhances cell motility
      and promotes lymphangiogenesis and lymphatic metastasis through the TLR4- NF
      kappaB/JNK pathways in colorectal cancer.
AB  - Lipopolysaccharide (LPS) exists in the outer membrane of Gram-negative bacteria.
      Colorectal normal epithelium and colorectal cancer cells in situ are continuously
      exposed to LPS from intestinal bacteria, while little is known about the
      influence of LPS on colorectal cancer progression and metastasis. In this study,
      we investigated the potential role of LPS on colorectal cancer progression and
      metastasis as well as the underlying mechanisms. We measured higher LPS
      concentration in colorectal cancer tissues and even higher LPS concentration in
      colorectal cancer tissues with lymph node metastasis. LPS significantly enhanced
      cancer cell motility and promoted human dermal lymphatic endothelial cells'
      (HDLECs') capacity of tube-like formation in vitro, as well as accelerates
      lymphangiogenesis and lymph node metastasis in nude mice. Furthermore, we
      demonstrated LPS notably increased the expression of VEGF-C in a time-dependent
      and concentration-dependent manner. VEGF-C is a key regulator for
      lymphangiogenesis and lymph node metastasis. By constructing lentivirus-mediated
      shVEGF-C cells, VEGF-C down-regulation suppressed LPS' promotive effect on cancer
      cell motility and HDLEC tube-like formation capacity. In addition, we found TLR4-
      NF-kappaB/JNK signal pathways were important for LPS to increase VEGF-C
      expression. All these result suggested a critical role for LPS in migration,
      invasion, lymphangiogenesis and lymph node metastasis of colorectal cancer,
      providing evidence that LPS increased VEGF-C secretion to promote cell motility
      and lymphangiogenesis via TLR4- NF-kappaB/JNK signaling.

PMID- 27713161
TI  - Role of long noncoding RNA UCA1 as a common molecular marker for lymph node
      metastasis and prognosis in various cancers: a meta-analysis.
AB  - Accumulating evidences indicated that UCA1 expression was up-regulated in various
      cancers, and high UCA1 expression was correlated with metastasis and prognosis.
      This meta-analysis collected all eligible studies and explored the relationships
      between UCA1 expression and lymph node metastasis (LNM) or overall survival (OS).
      Literature collection was performed by using electronic databases PubMed,
      Cochrane Library, and Web of Science (up to June 13, 2016). According to the
      inclusion and exclusion criteria, twelve studies were included in the meta
      analysis. The result showed that high UCA1 expression was correlated with more
      LNM (OR=2.50, 95 %CI: 1.58-3.96, p<0.0001) in a random-effects model (I2=45 %,
      p=0.08) and could predict poor OS in cancer patients, with pooled hazard ratio
      (HR) of 1.65 [95% confidence interval (CI) 1.44-1.88, p<0.00001] indicated by a
      fixed-effects model (I2=35%, p=0.11). In conclusion, the present meta-analysis
      demonstrated that high expression of UCA1 might serve as a common molecular
      marker for predicting lymph node metastasis and prognosis in various cancers.

PMID- 27713162
TI  - MTOR inhibition reversed drug resistance after combination radiation with
      erlotinib in lung adenocarcinoma.
AB  - OBJECTIVE: To investigate the effects of mTOR inhibition on drug resistance in
      lung adenocarcinoma after combined radiation and erlotinib therapy. RESULTS:
      Combined radiation and erlotinib therapy produced clear radiosensitization
      effects both in vitro and in vivo; however, tumor cells remained drug resistant.
      Additionally, combined radiation and erlotinib therapy significantly increased p
      AKT and p-P70 levels. After mTOR inhibition, the number of surviving cells
      significantly decreased compared with that before inhibition, and the in vivo
      growth curve was significantly reduced. METHODS: The effects of combined
      radiation and erlotinib therapy on tumor inhibition and drug resistance were
      evaluated by in vitro survival curves in PC9 lung adenocarcinoma cell line and in
      vivo growth curves in nude mouse xenograft tumor model respectively. The
      association between tumor drug resistance and the phosphatidylinositol 3
      kinase/protein kinase B/mechanistic target of rapamycin (PI3K-AKT-mTOR) pathway
      was measured by western blot, assessing the changes in protein kinase B (AKT),
      phosphor-AKT (p-AKT), P70, and p-P70 protein levels. MTOR was inhibited using
      everolimus, and changes in AKT, p-AKT, P70, and p-P70 levels were observed.
      Furthermore, changes in in vitro survival curves, and in vivo growth curves
      before and after mTOR inhibition were evaluated to confirm its effects on drug
      resistance in lung adenocarcinoma after combined radiation and TKI therapy.
      CONCLUSION: mTOR was associated with drug resistance in lung adenocarcinoma after
      radiation combined with TKI, and MTOR inhibition reversed drug resistance in lung
      adenocarcinoma after combined radiation and TKI therapy.

PMID- 27713160
TI  - Role of BCL9L in transforming growth factor-beta (TGF-beta)-induced epithelial-to
      mesenchymal-transition (EMT) and metastasis of pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has a low overall survival rate, which is
      approximately 20% during the first year and decreases to less than 6% within five
      years of the disease. This is due to premature dissemination accompanied by a
      lack of disease-specific symptoms during the initial stages. Additionally, to
      date there are no biomarkers for an early prognosis available.A growing number of
      studies indicate that epithelial to mesenchymal transition (EMT), triggered by
      WNT-, TGF-beta- and other signaling pathways is crucial for the initiation of the
      metastatic process in PDAC. Here we show, that BCL9L is up-regulated in PDAC cell
      lines and patient tissue compared to non-cancer controls. RNAi-induced BCL9L
      knockdown negatively affected proliferation, migration and invasion of pancreatic
      cancer cells. On a molecular basis, BCL9L depletion provoked an increment of E
      cadherin protein levels, with concomitant increase of beta-catenin retention at
      the plasma membrane. This is linked to the induction of a strong epithelial
      phenotype in pancreatic cancer cells upon BCL9L knockdown even in the presence of
      the EMT-inducer TGF-beta. Finally, xenograft mouse models of pancreatic cancer
      revealed a highly significant reduction in the number of liver metastases upon
      BCL9L knockdown. Taken together, our findings underline the key importance of
      BCL9L for EMT and thus progression and metastasis of pancreatic cancer cells.
      Direct targeting of this protein might be a valuable approach to effectively
      antagonize invasion and metastasis of PDAC.

PMID- 27713164
TI  - Upregulation of HSF1 in estrogen receptor positive breast cancer.
AB  - Heat shock transcription factor 1 (HSF1), a key regulator of the heat-shock
      response, is deregulated in many cancers. HSF1 can mediate cancer cell survival
      and metastasis. High levels of HSF1 have been associated with poor prognosis in
      breast cancer. The nature of HSF1 upregulation needs to be validated in different
      cohorts to further validate its prognostic utility in breast cancer.We first
      evaluated its expression in a cohort of breast cancer tissue microarrays with
      Oncotype DX recurrence scores available using immunohistochemistry. To further
      confirm the clinical relevance and prognostic impact, mutational and methylation
      status of the gene were also assessed in The Cancer Genome Atlas and publically
      available microarray datasets.Immunohistochemical analysis showed that HSF1
      expression is independent of Oncotype DX high recurrence score in ER-positive
      node-negative patients. Analysis of The Cancer Genome Atlas data revealed
      upregulation of HSF1 is not due to methylation or mutation. HSF1 copy number
      variations and amplifications (15%) were not associated with survival. In
      publicly available microarray datasets, a prognostic impact was observed in ER
      positive tumors, but not in ER-negative tumors. Patients with ER-positive tumors
      with high HSF1 levels were associated with shorter overall survival (P = 0.00045)
      and relapse-free survival (P = 0.0057). In multivariable analysis, HSF1 remained
      a significant prognostic parameter.The mRNA expression levels of HSF1 in ER
      positive breast cancer are associated with both shorter relapse-free and overall
      survival. This prognostic impact is specific to mRNA expression, but stayed
      insignificant by protein expression or by analyzing amplification events.

PMID- 27713163
TI  - Premalignant alteration assessment in liver-like tissue derived from embryonic
      stem cells by aristolochic acid I exposure.
AB  - The in vitro predictive evaluation of chemical carcinogenicity based on hepatic
      premalignance has so far not been established. Here, we report a novel approach
      to investigate the premalignant events triggered by human carcinogen aristolochic
      acid I (AAI) in the liver-like tissue derived from mouse embryonic stem cells. By
      AAI exposure, the liver-like tissue exhibited the paracrine interleukin-6
      phenotypic characteristics. Hepatocytes expressed STAT3/p-STAT3, c-Myc and Lin28B
      in parallel. Some of them displayed the dedifferentiation characteristics, such
      as full of alpha-fetoprotein granules, increase in size, and nucleocytoplasmic
      shuttle of Oct4. When these cells were injected into mice, the xenografts mostly
      displayed the uniform area of hepatic-like tissue with malignant nuclei. The
      hepatic malignant markers, alpha-fetoprotein, cytokeratin 7 and cytokeratin 19,
      were co-expressed in albumin-positive areas, respectively. In conclusion, we
      established an approach to predict the hepatic premalignance triggered by
      carcinogen AAI. This premalignant assay system might aid to evaluate the effects
      of potential carcinogens in liver, and probably to screen the protecting against
      hepatocarcinogenic efficacy of pharmaceuticals in vitro.

PMID- 27713165
TI  - Generation of V alpha13/beta21+T cell specific target CML cells by TCR gene
      transfer.
AB  - Adoptive immunotherapy with antigen-specific T cells can be effective for
      treating melanoma and chronic myeloid leukemia (CML). However, to obtain
      sufficient antigen-specific T cells for treatment, the T cells have to be
      cultured for several weeks in vitro, but in vitro T cell expansion is difficult
      to control. Alternatively, the transfer of T cell receptors (TCRs) with defined
      antigen specificity into recipient T cells may be a simple solution for
      generating antigen-specific T cells. The objective of this study was to identify
      CML-associated, antigen-specific TCR genes and generate CML-associated, antigen
      specific T cells with T cell receptor (TCR) gene transfer. Our previous study has
      screened an oligoclonal Vbeta21 with a different oligoclonal Valpha partner in
      peripheral blood mononuclear cells (PBMCs) derived from patients with CML. In
      this study, oligoclonally expanded TCR alpha genes, which pair with TCR Vbeta21,
      were cloned into the pIRES eukaryotic expression vector (TCR Valpha-IRES
      Vbeta21). Next, two recombinant plasmids, TCR Valpha13-IRES-Vbeta21 and TCR
      Valpha18-IRES-Vbeta21, were successfully transferred into T cells, and the TCR
      gene-modified T cells acquired CML-specific cytotoxicity with the best cytotoxic
      effects for HLA-A11+ K562 cells observed for the TCR Valpha13/Vbeta21 gene
      redirected T cells. In summary, our data confirmed TCRValpha13/Vbeta21 as a CML
      associated, antigen-specific TCR. This study provided new evidence that
      genetically engineered antigen-specific TCR may become a druggable approach for
      gene therapy of CML.

PMID- 27713166
TI  - MFAP5 and TNNC1: Potential markers for predicting occult cervical lymphatic
      metastasis and prognosis in early stage tongue cancer.
AB  - The purpose of this study is to identify candidate genes that could predict
      prognosis of early-stage tongue squamous cell carcinoma (TSCC) and its occult
      cervical lymphatic metastasis by large-scale gene expression profiling. Tumor
      tissue and matched normal mucosa samples were collected from patients with TSCC
      and analyzed with Affymetrix HTA2.0 high-density oligonucleotide array.
      Differentially expressed genes in TSCC with cervical lymph node metastasis (CLNM)
      were further analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and
      Genomes for their functions and related pathways. A total of 107 differentially
      expressed genes (p < 0.05) were identified by microarray in TSCC samples with
      CLNM (n = 6) compared to those without CLNM (n = 6). Genes involved in the cell
      matrix adherens junction and migration function including MFAP5, TNNC1, MGP,
      FBFBP1 and FBXO32 were selected and validated by RT-PCR in TSCC samples (n = 32).
      Of the five genes, MFAP5 and TNCC1 expressions were further validated by
      immohistochemistry (n = 61). The significant positive correlation between MFAP5
      and TNNC1 expression (p<0.001) was observed. Notably, over-expression of MFAP5
      and TNNC1 were correlated with CLNM, metastasis relapse-free survival and overall
      survival. Our findings indicated that MFAP5 and TNNC1 may be potential markers
      for predicting occult cervical lymphatic metastasis and prognosis of oral tongue
      carcinoma.

PMID- 27713167
TI  - Simultaneous high expression of PLD1 and Sp1 predicts a poor prognosis for
      pancreatic ductal adenocarcinoma patients.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with few therapeutic
      options. Recently, insight into cancer biology suggested abnormal lipid
      metabolism to be a risk factor for human malignancies. As a key enzyme implicated
      in lipid metabolism, PLD1 was elevated in various human cancer associating with
      malignant phenotypes. However, little was known about its expression and function
      in PDAC. We showed that PLD1 was elevated in both the cell lines and clinical
      samples of PDAC, and it positively correlated with vascular invasion (p = 0.041)
      and responsible for a poor prognosis (p = 0.009). Meanwhile, we also found Sp1 to
      be elevated in the disease, correlating with vascular invasion (p = 0.007).
      Moreover, the correlation assay suggested that PLD1 positively correlated with
      Sp1 in the clinical sample (r = 0.390; p < 0.001) and the cell lines. Finally, we
      showed that co-high expression of both the factors confers the poorest prognosis
      for the patients, and that their simultaneous high expression might be an
      independent prognostic factor (p = 0.001; HR = 3.427; 95% CI 1.629-7.211).

PMID- 27713168
TI  - The Aurora kinase A inhibitor TC-A2317 disrupts mitotic progression and inhibits
      cancer cell proliferation.
AB  - Mitotic progression is crucial for the maintenance of chromosomal stability. A
      proper progression is ensured by the activities of multiple kinases. One of these
      enzymes, the serine/threonine kinase Aurora A, is required for proper mitosis
      through the regulation of centrosome and spindle assembly. In this study, we
      functionally characterized a newly developed Aurora kinase A inhibitor, TC-A2317.
      In human lung cancer cells, TC-A2317 slowed proliferation by causing aberrant
      formation of centrosome and microtubule spindles and prolonging the duration of
      mitosis. Abnormal mitotic progression led to accumulation of cells containing
      micronuclei or multinuclei. Furthermore, TC-A2317-treated cells underwent
      apoptosis, autophagy or senescence depending on cell type. In addition, TC-A2317
      inactivated the spindle assembly checkpoint triggered by paclitaxel, thereby
      exacerbating mitotic catastrophe. Consistent with this, the expression level of
      Aurora A in tumors was inversely correlated with survival in lung cancer
      patients. Collectively, these data suggest that inhibition of Aurora kinase A
      using TC-A2317 is a promising target for anti-cancer therapeutics.

PMID- 27713169
TI  - A phase 1 study of oral ridaforolimus in pediatric patients with advanced solid
      tumors.
AB  - PURPOSE: Ridaforolimus is an investigational, potent, selective mTOR inhibitor.
      This study was conducted to determine the recommended phase 2 dose (RP2D),
      maximum tolerated dose, safety, pharmacokinetics, and antitumor activity of oral
      ridaforolimus in children with advanced solid tumors. EXPERIMENTAL DESIGN: In
      this phase 1, multicenter, open-label study in children aged 6 to <18 years with
      advanced solid tumors, ridaforolimus was administered orally for 5 consecutive
      days/week in 28-day cycles until progression, unacceptable toxicity, or consent
      withdrawal. Dose started at 22 mg/m2 and increased to 28 mg/m2 and 33 mg/m2,
      followed by expansion at the RP2D. RESULTS: Twenty patients were treated; 18 were
      evaluable for dose-limiting toxicities. One dose-limiting toxicity (grade 3
      increased alanine aminotransferase) occurred in 1 patient at 33 mg/m2. Dose
      escalation concluded at 33 mg/m2; the maximum tolerated dose was not determined.
      The most common treatment-related adverse events (frequency >=40%) were
      manageable grade 1-2 stomatitis, thrombocytopenia, hypertriglyceridemia,
      increased alanine aminotransferase, fatigue, hypercholesterolemia, anemia, and
      increased aspartate aminotransferase. Ridaforolimus exposure at 28 mg/m2 and 33
      mg/m2 exceeded adult target levels. The RP2D for oral ridaforolimus in children
      was defined as 33 mg/m2. Four patients received at least 4 cycles; 2 with
      pineoblastoma and diffuse intrinsic pontine glioma had stable disease for 12 and
      46 cycles, respectively. CONCLUSIONS: Ridaforolimus is orally bioavailable and
      well tolerated in children with advanced solid tumors. The RP2D (33 mg/m2, 5
      days/week) exceeds the adult RP2D. The favorable toxicity and pharmacokinetic
      profiles may allow for combination therapy, a promising therapeutic option in
      pediatric malignancies.

PMID- 27713170
TI  - Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2
      signaling.
AB  - Ultra Violet (UV) radiation induces reactive oxygen species (ROS) production, DNA
      oxidation and single strand breaks (SSBs), which will eventually lead to skin
      cell damages or even skin cancer. Here, we tested the potential activity of
      gremlin, a novel vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2)
      agonist, against UV-induced skin cell damages. We show that gremlin activated
      VEGFR2 and significantly inhibited UV-induced death and apoptosis of skin
      keratinocytes and fibroblasts. Pharmacological inhibition or shRNA-mediated
      knockdown of VEGFR2 almost abolished gremlin-mediated cytoprotection against UV
      in the skin cells. Further studies showed that gremlin activated VEGFR2
      downstream NF-E2-related factor 2 (Nrf2) signaling, which appeared required for
      subsequent skin cell protection. Nrf2 shRNA knockdown or S40T dominant negative
      mutation largely inhibited gremlin-mediated skin cell protection against UV. At
      last, we show that gremlin dramatically inhibited UV-induced ROS production and
      DNA SSB formation in skin keratinocytes and fibroblasts. We conclude that gremlin
      protects skin cells from UV damages via activating VEGFR2-Nrf2 signaling. Gremlin
      could be further tested as a novel anti-UV skin protectant.

PMID- 27713171
TI  - Sulfuretin promotes osteoblastic differentiation in primary cultured osteoblasts
      and in vivo bone healing.
AB  - Although sulfuretin, the major flavonoid of Rhus verniciflua Stokes, has a
      variety of biological actions, its in vitro and in vivo effects on osteogenic
      potential remain poorly understood. The objective of the present study was to
      investigate the effects of sulfuretin on in vitro osteoblastic differentiation
      and the underlying signal pathway mechanisms in primary cultured osteoblasts and
      on in vivo bone formation using critical-sized calvarial defects in mice.
      Sulfuretin promoted osteogenic differentiation of primary osteoblasts, with
      increased ALP activity and mineralization, and upregulated differentiation
      markers, including ALP, osteocalcin, and osteopontin, in a concentration
      dependent manner. The expression levels of Runx2, BMP-2, and phospho-Smad1/5/8
      were upregulated by sulfuretin. Moreover, sulfuretin increased phosphorylation of
      Akt, mTOR, ERK, and JNK. Furthermore, sulfuretin treatment increased mRNA
      expression of Wnt ligands, phosphorylation of GSK3, and nuclear beta-catenin
      protein expression. In vivo studies with calvarial bone defects revealed that
      sulfuretin significantly enhanced new bone formation by micro-computed tomography
      and histologic analysis. Collectively, these data suggest that sulfuretin acts
      through the activation of BMP, mTOR, Wnt/beta-catenin, and Runx2 signaling to
      promote in vitro osteoblast differentiation and facilitate in vivo bone
      regeneration, and might be have therapeutic benefits in bone disease and
      regeneration.

PMID- 27713173
TI  - Dot1l expression predicts adverse postoperative prognosis of patients with clear
      cell renal cell carcinoma.
AB  - BACKGROUND: Disruptor of telomeric silencing 1-like (Dot1l), a histone
      methyltransferase that targets the histone H3 lysine 79 (H3K79), has been
      reported that its high expression is associated with various cancers, while the
      association between Dot1l expression and clear-cell renal cell carcinoma (ccRCC)
      is still unknown. PATIENTS AND METHODS: We retrospectively enrolled 282 patients
      with ccRCC undergoing nephrectomy from a single institution between 2005 and
      2007, with a median follow-up of 99 months. Dot1l expression was evaluated by
      immunohistochemistry in clinical specimens. We compared the clinical outcomes by
      Kaplan-Meier survival analyses and assessed the prognostic value of Dot1l
      expression. Harrell's concordance index (C-index) was used to assess the
      predictive accuracy of different prognostic models. RESULTS: Higher Dot1l
      expression indicated poorer OS (P<0.001) and RFS (P<0.001) in patients with
      ccRCC. Moreover, Dot1l expression could stratify ccRCC patients in pT stage,
      Fuhrman grade and SSIGN/ Leibovich subgroups, which might redefine individual
      risk stratification. Multivariate analyses further indicated that Dot1l
      expression was an independent prognostic factor for OS (P=0.007) and RFS
      (P=0.001). The prognostic accuracy of conventional prognostic models was notably
      improved with Dot1l integration. Two nomograms and calibration plots were built
      to predict OS and RFS for patients with ccRCC and performed better based on C
      index value. CONCLUSION: Dot1l expression is a promising independent prognostic
      indicator for postoperative recurrence and survival of patients with ccRCC.

PMID- 27713174
TI  - Protective effects of oxymatrine against arsenic trioxide-induced liver injury.
AB  - Oxymatrine, a quinolizidine natural drug extracted from Sophora japonica, has
      been reported to have neuroprotective effect and cardioprotective effect.
      However, the protective effect of oxymatrine on arsenic trioxide (As2O3)-induced
      liver injury has not been reported. In the present study, we investigated the
      protective effects of oxymatrine on As2O3-induced liver injury in rats. Male
      Wistar rats were administrated 3mg/kg As2O3 intravenous injection on alternate
      days for 4 days. Oxymatrine was given 1 h before As2O3 treatment. The results
      showed that oxymatrine inhibited As2O3-induced hepatic pathological damage, liver
      ROS level and MDA level in a dose-dependent manner. As2O3 decreased the
      antioxidant enzymes SOD, GPX, and CAT activity and the decrease was inhibited by
      treatment of oxymatrine. Furthermore, oxymatrine attenuated the retention of
      arsenic in liver tissues and improved the expression of Nrf2 and HO-1. In
      conclusion, our results suggested that oxymatrine protected against As2O3-induced
      oxidative damage by activating Nrf2/HO-1 signaling pathway.

PMID- 27713172
TI  - Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette
      smoke-exposed mice.
AB  - Cigarette smoke (CS) is known to dysregulate microRNA expression profiles in the
      lungs of mice, rats, and humans, thereby modulating several pathways involved in
      lung carcinogenesis and other CS-related diseases. We designed a study aimed at
      evaluating (a) the expression of 1135 microRNAs in the lung of Swiss H mice
      exposed to mainstream CS during the first 4 months of life and thereafter kept in
      filtered air for an additional 3.5 months, (b) the relationship between lung
      microRNA profiles and histopathological alterations in the lung, (c) intergender
      differences in microRNA expression, and (d) the comparison with microRNA profiles
      in blood serum. CS caused multiple histopathological alterations in the lung,
      which were almost absent in sham-exposed mice. An extensive microRNA
      dysregulation was detected in the lung of CS-exposed mice. Modulation of microRNA
      profiles was specifically related to the histopathological picture, no effect
      being detected in lung fragments with non-neoplastic lung diseases (emphysema or
      alveolar epithelial hyperplasia), whereas a close association occurred with the
      presence and multiplicity of preneoplastic lesions (microadenomas) and benign
      lung tumors (adenomas). Three microRNAs regulating estrogen and HER2-dependent
      mechanisms were modulated in the lung of adenoma-bearing female mice. Blood
      microRNAs were also modulated in mice affected by early neoplastic lesions.
      However, there was a poor association between lung microRNAs and circulating
      microRNAs, which can be ascribed to an impaired release of mature microRNAs from
      the damaged lung. Studies in progress are evaluating the feasibility of analyzing
      blood microRNAs as a molecular tool for lung cancer secondary prevention.

PMID- 27713175
TI  - Fatty acid synthase is a primary target of MiR-15a and MiR-16-1 in breast cancer.
AB  - Fatty acid synthase (FASN) is upregulated in breast cancer and correlates with
      poor prognosis. FASN contributes to mammary oncogenesis and serves as a bona fide
      target in cancer therapies. MicroRNAs inhibit gene expression through blocking
      mRNA translation or promoting mRNA degradation by targeting their 3'-UTRs. We
      identified four microRNAs in two microRNA clusters miR-15a-16-1 and miR-497-195
      that share a common seed sequence to target the 3'-UTR of the FASN mRNA. In
      reporter assays, both of these microRNA clusters inhibited the expression of a
      reporter construct containing the FASN 3'-UTR. However, only ectopic miR-15a-16
      1, but not miR-497-195, markedly reduced the levels of endogenous FASN in breast
      cancer cells. Both miR-15a and miR-16-1 contributes to inhibiting FASN expression
      and breast cancer cell proliferation. Consistently, a sponge construct consisting
      of eight repeats of the FASN 3'-UTR region targeted by these microRNAs could
      markedly increase endogenous FASN levels in mammary cells. When FASN expression
      was restored by ectopic expression in breast cancer cells, retarded cell
      proliferation caused by miR-15a-16-1 was partially rescued. In conclusion, we
      demonstrated that FASN expression is primarily downregulated by miR-15a and miR
      16-1 in mammary cells and FASN is one of the major targets of these two tumor
      suppressive microRNAs.

PMID- 27713176
TI  - A functional signal profiling test for identifying a subset of HER2-negative
      breast cancers with abnormally amplified HER2 signaling activity.
AB  - The results of clinical trials evaluating the efficacy of HER2 inhibitors in
      patients with breast cancer indicate that the correlation between HER2 receptor
      levels and patient outcomes is as low as 50%. The relatively weak correlation
      between HER2 status and response to HER2-targeting drugs suggests that
      measurement of HER2 signaling activity, rather than absolute HER2 levels, may
      more accurately diagnose HER2-driven breast cancer. A new diagnostic test, the
      CELx HER2 Signaling Profile (CELx HSP) test, is demonstrated to measure real-time
      HER2 signaling function in live primary cells. In the present study, epithelial
      cells extracted fresh from breast cancer patient tumors classified as HER2
      negative (HER2-, n = 34 of which 33 were estrogen receptor positive) and healthy
      subjects (n = 16) were evaluated along with reference breast cancer cell lines (n
      = 19). Live cell response to specific HER2 agonists (NRG1b and EGF) and
      antagonist (pertuzumab) was measured. Of the HER2- breast tumor cell samples
      tested, 7 of 34 patients (20.5%; 95% CI = 10%-37%) had HER2 signaling activity
      that was characterized as abnormally high. Amongst the tumor samples there was no
      correlation between HER2 protein status (by cell cytometry) and HER2 signaling
      activity (hyperactive or normal) (Regression analysis P = 0.144, R2 = 0.068). One
      conclusion is that measurement of HER2 signaling activity can identify a subset
      of breast cancers with normal HER2 receptor levels with abnormally high levels of
      HER2 signaling. This result constitutes a new subtype of breast cancer that
      should be considered for treatment with HER2 pathway inhibitors.

PMID- 27713180
TI  - The Kondo tip decorated by the Co atom.
AB  - The Kondo effect of single Co adatoms on Ru(0001) is detected with two different
      kinds of co-decorated tip (Kondo tip) by using low temperature scanning tunneling
      microscopy and scanning tunneling spectroscopy. We call the relatively separated
      two magnetic impurities in the tunneling region 'two Kondo system' to distinguish
      it from the 'two-impurity Kondo system'. We find that the artificially
      constructed Kondo tips can be generally categorized into two types of Kondo
      resonances, which have distinct Fano line shapes with quantum interference factor
      |q| ? 1 and |q| ~ 1, respectively. The tunneling spectra of six constructed two
      Kondo systems can be well fitted by summing the two Fano resonances of the two
      subsystems and a linear background. More interestingly, by extracting the
      amplitudes of the two Fano resonances in the spectra, we find that the electron
      transmission of such a two Kondo system in the tunneling region is dominated by
      the quantum interference of the Kondo tip, which is directly related to the
      geometric configuration of the adsorbed Kondo atom on the tip.

PMID- 27713177
TI  - LDB1 overexpression is a negative prognostic factor in colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in western
      countries and is driven by the Wnt signaling pathway. LIM-domain-binding protein
      1 (LDB1) interacts with the Wnt signaling pathway and has been connected to
      malignant diseases. We therefore aimed to evaluate the role of LDB1 in CRC.
      RESULTS: Overexpression of LDB1 in CRC is associated with strikingly reduced
      overall and metastasis free survival in all three independent patient cohorts.
      The expression of LDB1 positively correlates with genes involved in the Wnt
      signaling pathway (CTNNB1, AXIN2, MYC and CCND1). Overexpression of LDB1 in CRC
      cell lines induced Wnt pathway upregulation as well as increased invasivity and
      proliferation. Upon separate analysis, the role of LDB1 proved to be more
      prominent in proximal CRC, whereas distal CRC seems to be less influenced by
      LDB1. MATERIALS AND METHODS: The expression of LDB1 was measured via RT-qPCR in
      59 clinical tumor and normal mucosa samples and correlated to clinical end
      points. The role of LDB1 was examined in two additional large patient cohorts
      from publicly available microarray and RNAseq datasets. Functional
      characterization was done by lentiviral overexpression of LDB1 in CRC cell lines
      and TOP/FOP, proliferation and scratch assays. CONCLUSIONS: LDB1 has a strong
      role in CRC progression, confirmed in three large, independent patient cohorts.
      The in vitro data confirm an influence of LDB1 on the Wnt signaling pathway and
      tumor cell proliferation. LDB1 seems to have a more prominent role in proximal
      CRC, which confirms the different biology of proximal and distal CRC.

PMID- 27713178
TI  - Impact of Polo-like kinase 1 inhibitors on human adipose tissue-derived
      mesenchymal stem cells.
AB  - Polo-like kinase 1 (Plk1) has been established as one of the most promising
      targets for molecular anticancer intervention. In fact, various Plk1 inhibitors
      have been identified and characterized. While the data derived from the bench are
      prospective, the clinical outcomes are less encouraging by showing modest
      efficacy. One of the explanations for this discrepancy could be unintendedly
      targeting of non-malignant cells by Plk1 inhibitors. In this work, we have
      addressed the effect of Plk1 inhibition in adipose tissue-derived mesenchymal
      stem cells (ASCs). We show that both visceral and subcutaneous ASCs display
      monopolar spindles, reduced viability and strong apoptosis induction upon
      treatment with BI 2536 and BI 6727, the Plk1 kinase domain inhibitors, and with
      Poloxin, the regulatory Polo-box domain inhibitor. While Poloxin triggers quickly
      apoptosis, BI 2536 and BI 6727 result in mitotic arrest in ASCs. Importantly,
      survived ASCs exhibit DNA damage and a pronounced senescent phenotype. In
      addition, Plk1 inhibition impairs ASCs' motility and homing ability. These
      results show that Plk1 inhibitors target slowly proliferating ASCs, an important
      population of anti-inflammation and immune modulation. The toxic effects on
      primary cells like ASCs could be partially responsible for the reported moderate
      antitumor activity in patients treated with Plk1 inhibitors.

PMID- 27713181
TI  - Reduction of magnetic damping and isotropic coercivity and increase of saturation
      magnetization in Rh-incorporated CoIr system.
AB  - Replacing Ir with Rh in a CoIr system possessing negative uniaxial
      magnetocrystalline anisotropy (K u ) substantially reduces its magnetic damping
      and coercivity by more than half while retaining its high negative K u .
      Moreover, a higher saturation magnetization (M s ) and more isotropic coercivity
      are achieved. Such material development makes it particularly suitable for use as
      the soft underlayer (SUL) of magnetic recording media for reducing noise, and as
      the oscillation layer of a spin-torque oscillator (STO) for achieving higher
      oscillation frequency, larger AC magnetic field and lower driving current, which
      can be readily integrated with the current recording head for microwave-assisted
      magnetic recording. Finally, we recommend a composite free layer by coupling CoIr
      with a spin polarizer (Co or Co/Cu/Co) for the enhancement of the spin
      polarization rate and, therefore, the improvement of STO efficiency. These could
      pave the way for CoIr-based materials to be implemented in devices requiring a
      negative Ku with low damping and high 'softness', such as oscillators.

PMID- 27713179
TI  - The hedgehog inhibitor GANT61 sensitizes prostate cancer cells to ionizing
      radiation both in vitro and in vivo.
AB  - Limited data exists regarding the combination of Hedgehog signaling (Hh)
      inhibition and radiotherapy, even though there are several indications that this
      might be a promising treatment strategy. In this study, we evaluated the
      combination of two Hh inhibitors, the SMO inhibitor GDC-0449 and the GLI
      inhibitor GANT61 with radiotherapy in different prostate cancer (PCa) models. In
      vitro, GANT61 was able to sensitize 22Rv1 PCa cells but not PC3 and DU145 PCa
      cells. The lack of radiosensitization in the latter cell lines was shown to be
      dependent on the presence of mutated p53. Introduction of WT p53 into PC3 cells
      resulted in radiosensization following GANT61 treatment, suggesting that the p53
      transcription factor plays an important role in the GANT61-induced
      radiosensitization in vitro. Targeting at the level of SMO (GDC-0449) did not
      show cytotoxicity or synergy with radiation. Furthermore, we confirmed the
      radiosensitization effect of GANT61 in two in vivo xenograft PCa models. The
      decrease in tumor growth was associated with decreased proliferation and
      increased apoptosis. In conclusion, we provide evidence that GANT61 in
      combination with radiation treatment might represent a promising therapeutic
      strategy for enhancing the radiation response of PCa patients.

PMID- 27713182
TI  - Vertical Si nanowire arrays fabricated by magnetically guided metal-assisted
      chemical etching.
AB  - In this work, vertically aligned Si nanowire arrays were fabricated by
      magnetically guided metal-assisted directional chemical etching. Using an
      anodized aluminum oxide template as a shadow mask, nanoscale Ni dot arrays were
      fabricated on an Si wafer to serve as a mask to protect the Si during the
      etching. For the magnetically guided chemical etching, we deposited a tri-layer
      metal catalyst (Au/Fe/Au) in a Swiss-cheese configuration and etched the sample
      under the magnetic field to improve the directionality of the Si nanowire etching
      and increase the etching rate along the vertical direction. After the etching,
      the nanowires were dried with minimal surface-tension-induced aggregation by
      utilizing a supercritical CO2 drying procedure. High-resolution transmission
      electron microscopy (HR-TEM) analysis confirmed the formation of single-crystal
      Si nanowires. The method developed here for producing vertically aligned Si
      nanowire arrays could find a wide range of applications in electrochemical and
      electronic devices.

PMID- 27713183
TI  - Recombination dynamics in aerotaxy-grown Zn-doped GaAs nanowires.
AB  - In this paper we have investigated the dynamics of photo-generated charge
      carriers in a series of aerotaxy-grown GaAs nanowires (NWs) with different levels
      of Zn doping. Time-resolved photo-induced luminescence and transient absorption
      have been employed to investigate radiative (band edge transition) and non
      radiative charge recombination processes, respectively. We find that the photo
      luminescence (PL) lifetime of intrinsic GaAs NWs is significantly increased after
      growing an AlGaAs shell over them, indicating that an AlGaAs shell can
      effectively passivate the surface of aerotaxy-grown GaAs NWs. We observe that PL
      decay time as well as PL intensity decrease with increasing Zn doping, which can
      be attributed to thermally activated electron trapping with the trap density
      increased due to the Zn doping level.

PMID- 27713184
TI  - Quenching of the luminescence intensity of GaN nanowires under electron beam
      exposure: impact of C adsorption on the exciton lifetime.
AB  - Electron irradiation of GaN nanowires in a scanning electron microscope strongly
      reduces their luminous efficiency as shown by cathodoluminescence imaging and
      spectroscopy. We demonstrate that this luminescence quenching originates from a
      combination of charge trapping at already existing surface states and the
      formation of new surface states induced by the adsorption of C on the nanowire
      sidewalls. The interplay of these effects leads to a complex temporal evolution
      of the quenching, which strongly depends on the incident electron dose per area.
      Time-resolved photoluminescence measurements on electron-irradiated samples
      reveal that the carbonaceous adlayer affects both the nonradiative and the
      radiative recombination dynamics.

PMID- 27713185
TI  - Manipulation of single nanodiamonds to ultrathin fiber-taper nanofibers and
      control of NV-spin states toward fiber-integrated lambda-systems.
AB  - We report on the coupling of single nitrogen vacancy (NV) centers to ultrathin
      fiber-taper nanofibers by the manipulation of single diamond nanocrystals on the
      nanofibers under real-time observation of nanodiamond fluorescence. Spin
      dependent fluorescence of the single NV centers is efficiently detected through
      the nanofiber. We show control of the spin sub-level structure of the electronic
      ground state using an external magnetic field and clearly observe a frequency
      fine tuning of [Formula: see text]. This observation demonstrates a possibility
      of realizing fiber-integrated quantum lambda-systems, which can be used for
      various quantum information devices including push-pull quantum memory and
      quantum gates.

PMID- 27713186
TI  - Fluorescent protein integrated white LEDs for displays.
AB  - The usage time of displays (e.g., TVs, mobile phones, etc) is in general shorter
      than their functional life time, which worsens the electronic waste (e-waste)
      problem around the world. The integration of biomaterials into electronics can
      help to reduce the e-waste problem. In this study, we demonstrate fluorescent
      protein integrated white LEDs to use as a backlight source for liquid crystal
      (LC) displays for the first time. We express and purify enhanced green
      fluorescent protein (eGFP) and monomeric Cherry protein (mCherry), and afterward
      we integrate these proteins as a wavelength-converter on a blue LED chip. The
      protein-integrated backlight exhibits a high luminous efficacy of 248 lm/Wopt and
      the area of the gamut covers 80% of the NTSC color gamut. The resultant colors
      and objects in the image on the display can be well observed and distinguished.
      Therefore, fluorescent proteins show promise for display applications.

PMID- 27713187
TI  - Transforming gate misalignment into a unique opportunity to facilitate steep
      switching in junctionless nanotransistors.
AB  - In this work, we examine the feasibility of triggering impact ionisation at sub
      bandgap voltages through optimal utilisation of structural non-ideality induced
      electric field redistribution in the semiconductor film for an energy efficient
      steep switching junctionless (JL) transistor. While misalignment between front
      and back gates is often considered as a disadvantage due to loss of gate
      controllability, the work highlights its usefulness and applicability in
      nanoscale devices to engineer the electric field to enhance the product of
      current density (J) and electric field (E) and activate impact ionisation at sub
      bandgap applied voltages. Results show that intentionally misaligned gates in
      silicon and germanium based JL devices exhibit an inclined conduction channel and
      achieve a nearly ideal value of steep subthreshold swing (~ 1 mV decade-1) at
      room temperature. The work provides new viewpoints to realise energy efficient JL
      devices through the sharp increase of drain current from off-state to on-state
      achieved due to intentional misalignment between front and back gates.

PMID- 27713188
TI  - Interfaces and heterostructures of van der Waals materials.

PMID- 27713189
TI  - Anharmonic enhancement of superconductivity in metallic molecular Cmca  -  4
      hydrogen at high pressure: a first-principles study.
AB  - First-principles calculations based on density-functional theory including
      anharmonicity within the variational stochastic self-consistent harmonic
      approximation are applied to understand how the quantum character of the proton
      affects the candidate metallic molecular Cmca  -  4 structure of hydrogen in the
      400-450 GPa pressure range, where metallization of hydrogen is expected to occur.
      Anharmonic effects, which become crucial due to the zero-point motion, have a
      large impact on the hydrogen molecules by increasing the intramolecular distance
      by approximately a 6%. This induces two new electron pockets at the Fermi surface
      opening new scattering channels for the electron-phonon interaction.
      Consequently, the electron-phonon coupling constant and the superconducting
      critical temperature are approximately doubled by anharmonicity and Cmca  -  4
      hydrogen becomes a superconductor above 200 K in all the studied pressure range.
      Contrary to many superconducting hydrides, where anharmoncity tends to lower the
      superconducting critical temperature, our results show that it can enhance
      superconductivity in molecular hydrogen.

PMID- 27713190
TI  - Stretchable and transparent electrodes based on patterned silver nanowires by
      laser-induced forward transfer for non-contacted printing techniques.
AB  - Silver nanowires (AgNWs) are excellent candidate electrode materials in next
      generation wearable devices due to their high flexibility and high conductivity.
      In particular, patterning techniques for AgNWs electrode manufacture are very
      important in the roll-to-roll printing process to achieve high throughput and
      special performance production. It is also essential to realize a non-contact
      mode patterning for devices in order to keep the pre-patterned components away
      from mechanical damages. Here, we report a successful non-contact patterning of
      AgNWs-based stretchable and transparent electrodes by laser-induced forward
      transfer (LIFT) technique. The technique was used to fabricate a 100% stretchable
      electrode with a width of 200 MUm and electrical resistivity 10-4 Omegacm.
      Experiments conducted integrating the stretchable electrode on rubber substrate
      in which LED was pre-fabricated showed design flexibility resulting from non
      contact printing. Further, a patterned transparent electrode showed over 80% in
      optical transmittance and less than 100 Omega sq-1 in sheet resistance by the
      optimized LIFT technique.

PMID- 27713191
TI  - Not ery small bowel submucosal mass is a GIST A rare case of small bowel
      schwannoma.
AB  - INTRODUCTION: Schwannomas are slow-growing tumors, rarely occurring in the GI
      tract. When found, their location is mostly in the stomach. Presentation in the
      small bowel is extremely rare, anecdotal. CASE REPORT: We present the case of a
      47-year old male who underwent laparoscopic elective left hemicolectomy for
      recurrent diverticulitis. RESULTS: At surgery an exophytic mass originating from
      the first jejunal loop was identified and resected, under the suspicion of a
      GIST. Post-operative pathologic report was consistent with the diagnosis of
      jejunal schwannoma. Unfortunately resection margins were positive and the patient
      was taken back to the OR for an additional jejunal segmental resection.
      CONCLUSIONS: GI schwannomas have excellent prognosis after surgical resection. It
      is important to differentiate them from GISTs, which may have a malignant
      behavior in 10-30% of the cases. To ensure complete surgical resection with
      negative margins is mandatory and is the curative treatment of choice. KEY WORDS:
      GIST, Jejunum, Submucosa Minimally-invasive surgery, Schwannoma, Small bowel.

PMID- 27713193
TI  - [Prevention and Treatment Strategy for Infectious Complication after Lung
      Transplantation].
AB  - The most frequent cause of death within a year after lung transplantation is
      infectious complications, which shifts to chronic allograft rejection or chronic
      lung allograft dysfunction(CLAD) thereafter. It is no doubt that minimization of
      the dose of immunosuppression within the acceptable therapeutic range is a best
      strategy to avoid infectious complications however, adequate dose of
      immunosuppressant is mandatory to protect lung allografts from acute or chronic
      rejection. Carefully balanced therapy of immunosuppression and infection control
      is extremely important for patient's long term survival after lung
      transplantation. Total 344 transplants were performed in Japan until the end of
      2013, and the 5-year post-operative survival was reported as more than 70% which
      is superior than North American or European registry data. However, more than 30%
      of death is still caused by infectious complications thus appropriate prevention
      and treatment for infection is important for better long term results. Here in
      this paper, the 1st 10-year experience of Fukuoka University Lung Transplant
      Program was reported and discussed especially focusing on infectious
      complications.

PMID- 27713192
TI  - [Infectious Diseases after Lung Transplantation].
AB  - Lung transplantation is getting to be a common treatment for the end-stage
      respiratory failure. Therefore we might encounter the various issues associated
      with infection under immunosuppression. At 1st, virus infections occur by
      Cytomegalovirus, Epstein-Barr virus, hepatitis B and C virus and John Cunningham
      virus. The 2nd, bacterial infections exacerbate graft condition by methicillin
      resistant Staphylococcus aureus, Pseudomonas, Burkholderia cepacia and coagulase
      negative staphylococci. The 3rd, fungal infections are induced by Aspergillus,
      Candida and Cryptococcus. Lastly there is mycobacterial infection. These
      opportunistic infections contribute poor prognosis for lung transplant
      recipients, so that we have to manage these infectious diseases.

PMID- 27713195
TI  - [Cardiac Function after Lung Transplantation of Eisenmenger Syndrome].
AB  - Eisenmenger syndrome(ES) could occur at the end-stage of congenital heart disease
      and is one of the indications for lung transplantation. Survival following heart
      lung transplantation is better than that following bilateral lung transplantation
      (LT). However, in Japan, because of limitations in regard to the numbers of
      donors available, LT with cardiac repair is usually chosen. Following LT with
      cardiac repair, careful management of the repaired heart is necessary, though
      there are few reports available regarding such postoperative cardiac management.
      Here, we present findings from careful postoperative monitoring and management of
      cardiac function in a patient with ES with a ventricular septal defect, for whom
      LT with cardiac repair was performed. In addition, follow-up results of cardiac
      function are presented as well as discussion of important points related to such
      cases.

PMID- 27713194
TI  - [Anti-thymocyte Globulin Therapy for Cases of Acute Rejection Following Lung
      Transplantation].
AB  - A 58-year-old male underwent right lung transplantation from a brain-dead donor,
      after which acute rejection developed that was resistant to steroid pulse
      therapy. Rabbit-derived anti-thymocyte globulin (rATG) therapy was successful for
      controlling the rejection. However, following that therapy, the patient was
      affected by an opportunistic infection and suffered from repeated empyema. It is
      important to pay attention to immunosuppressive agent levels in blood following
      treatment, because ATG is a potent immunosuppressive drug and its effects can
      continue for more than 6 months after administration.

PMID- 27713196
TI  - [Overview of Clinical Issues after Lung Transplantation].
AB  - Lung allograft encounters changeable issues over the pre-and postransplant
      period. It is important to realize individual problems in each specific
      peritransplant stage and share the awareness between transplant team and
      patients. Long-sighted management policy is encouraged throughout posttransplant
      care because morbidities in each stage trigger each other and graft condition and
      management in acute posttransplant period have a considerable impact on long-term
      recipient survival after lung transplantation. The specific issues at hand are
      reviewed by going through the current important literature.

PMID- 27713197
TI  - [Anastomotic Airway Complications after Lung Transplantation].
AB  - Anastomotic airway complications still remain an important issue after lung
      transplantation. Most of the complications are stenosis and anastomotic leakage.
      Stent insertion is one option for the stenosis. We review the anastomotic airway
      complications and report our recent experience of stent insertion using 3
      dimensional printed airway model.

PMID- 27713198
TI  - [The History and Development of Experimental Rodent Models of Chronic Lung
      Allograft Dysfunction after Lung Transplantation].
AB  - Chronic lung allograft dysfunction (CLAD) is a critical impediment to the long
      term survival after lung transplantation. A rat orthotopic lung transplantation
      model was developed in the early 1970s, and using this model, our laboratory has
      shown that the immunopathogenesis of CLAD involves both allogeneic immunity and
      autoimmunity. However, further investigation of CLAD is limited by the scarcity
      of transgenic and knockout strains. The model most widely used to study CLAD, the
      mouse model of heterotopic tracheal transplantation, has some incomplete
      pathophysiologic features of CLAD, which limits the utility of this model. Unlike
      other solid organ transplants, vascularized and aerated murine lung
      transplantation has only recently been developed. We have also reported that
      minor, but not major, histocompatibility antigens mismatch induced the
      development of CLAD in murine orthotopic lung transplants and that CLAD
      development was interleukin-17-dependent. This mini-review underscores the
      history and development of rodent models of CLAD after lung transplant, including
      the findings from our previous studies. In addition, the future direction of
      rodent models is also discussed.

PMID- 27713199
TI  - [Development of Personalized and Targeted Preventive Therapies for Chronic Lung
      Allograft Dysfunction Subtypes;A Novel Strategy].
AB  - Chronic lung allograft dysfunction (CLAD) is a major limitation to long-term
      success of lung transplantation. Restrictive allograft syndrome (RAS) is a
      recently discovered subtype of CLAD, showing distinct clinical, pathological and
      radiological features compared with the major CLAD subtype, bronchiolitis
      obliterans syndrome (BOS). Introduction of the novel CLAD classification system
      that differentiates CLAD into BOS and RAS has stimulated research activities
      aiming delineation of the underlying pathological mechanism in the 2 CLAD
      subtypes. Accumulating evidences suggest that BOS and RAS could be biologically
      distinct, indicating that optimal therapeutic strategy could be different.
      Further efforts in refinements in biologic profiling of BOS and RAS will lead to
      a better understanding of CLAD, as well as the development of personalized and
      targeted preventive therapies for underlying CLAD subtypes.

PMID- 27713200
TI  - [Characteristics of Postoperative Malignancies after Lung Transplantation].
AB  - Patients after lung transplantation are at risk for postoperative malignancy
      mainly due to postoperative immunosuppression. Skin cancer and post-transplant
      lymphoproliferative disorder (PTLD) are common in Western countries. We
      retrospectively reviewed the medical records of 120 patients undergoing lung
      transplantation between April 2002 and July 2015 at Kyoto University.
      Postoperative malignancy developed in 14 patients(11.7%):PTLD in 8, gastric
      cancer in 2, breast cancer in 1, glioblastoma in 1, lung cancer in 1, and
      adenocarcinoma of unknown primary in 1. Seven patients(11.3%)and 7 patients
      (12.1%)were after living-donor lung transplantation( LDLLT) and cadaveric lung
      transplantation (CLT), respectively (p=1.00). The overall 5-year survival of
      patients with postoperative malignancy was 39.3%, which tended to be worse
      (p=0.059), compared to those without postoperative malignancy(71.4%). All
      postoperative malignancies were de novo malignancies without any recurrence of
      original malignancies. Postoperative malignancies occurred after LDLLT as well as
      after CLT, and seemed to have a negative impact on long-term outcome of lung
      transplant recipients. The majority was PTLD;however, skin cancer was not
      recognized, suggesting ethnic differences. We should be careful about
      postoperative malignancies in follow-up of the lung transplant recipients.

PMID- 27713201
TI  - [Fatal Respiratory Failure Developed during Chemotherapy for Diffuse Large B Cell
      Lymphoma that Occurred Late after Lung Transplantation].
AB  - We report here a case of fatal respiratory failure developed during chemotherapy
      for diffuse large B cell lymphoma that occurred late after lung transplantation.
      25-year- old man underwent lung transplantation from brain death donor for
      respiratory failure due to interstitial pneumonia at the age of 16 years old. Two
      years after transplantation, his respiratory function decreased gradually.
      Chronic lung allograft dysfunction including bronchiolitis obliterans( BOS) and
      restrictive allograft syndrome was suspected and immunosuppression was enhanced.
      Nine years after transplantation, he had abdominal pain and physical examination
      suggested intestinal obstruction. Small intestine endoscopy revealed an ulcer at
      jejunum and diffuse large B cell lymphoma( DLBCL) was finally diagnosed by
      biopsy. Chemotherapy was planned for lymphoma, but respiratory failure progressed
      just before chemotherapy. Chest computed tomography showed infiltrative shadow in
      right lung, so we suspected presence of lymphoma and chemotherapy was carried
      out. After chemotherapy, abnormal shadow in the right lung disappeared. Although
      chemotherapy was effective, respiratory failure progressed and he died.
      Pathological examination from autopsy showed mixture of BOS, diffuse alveolar
      damage, invasion of aspergillus and acute fibrinoid organizing pneumonia but no
      residual DLBCL was found in the lung.

PMID- 27713202
TI  - [Unplanned Ascending Aortic Graft Replacement at Valvuler Surgery in a Patient
      with Systemic Lupus Erythematosus;Report of a Case].
AB  - A 65-year-old woman with severe mitral stenosis was admitted to our hospital. She
      had been previously diagnosed with systemic lupus erythematosus (SLE) and had
      been taking prednisolone (5 mg/day) for 19 years. As SLE patients with prolonged
      steroid use are known to be at risk of an aortic dissection and aneurysm, femoral
      artery was chosen for arterial perfusion to reduce the risk of a dissection of
      the ascending aorta. However, hemostasis was difficult at the insertion point of
      the catheter to infuse the antegrade cardioplegic solution. An ascending aortic
      graft replacement was therefore performed. Histopathological examination of the
      aortic wall showed the presence of intimal hypertrophy and a decrease in elastic
      fiber content but without any evidence of vasculitis. Because prolonged steroids
      use is a risk factor of atherosclerotic change in the aortic wall, the aorta
      should be treated carefully during cardiovascular surgery in such patients.

PMID- 27713203
TI  - [Left Ventricular Patch Plasty for Post-infarct Ventricular True Aneurysm with
      Ventricular Septal Perforation;Report of a Case].
AB  - We experienced a rare case of post-infarct left ventricular aneurysm (LVA) and
      ventricular septal perforation (VSP). An 83-year-old woman was treated for acute
      cardiac insufficiency. Three weeks later after hospitalization, she had sudden
      cardiorespiratory failure and was diagnosed with VSP and LVA. She underwent
      emergency heart surgery. After establishing extracorporeal circulation, the LVA
      was excised longitudinally from the left side of the left anterior descending
      branch. Endoventricular patch plasty (Dor procedure) was performed to exclude the
      ventricular aneurysm, and the VSP was closed using Dacron patch. After surgery,
      echocardiography found no residual shunts and exclusion of the LVA. The patient
      underwent successful surgical treatment of VSP and LVA.

PMID- 27713204
TI  - [Rupture of Saccular Brachiocephalic Artery Aneurysm after One Year and Seven
      Months from Coil Embolization;Report of a Case].
AB  - A 52-years-old man, who had undergone coil embolization of saccular aneurysm of
      the brachiocephalic artery, presented with right back discomfort. Diagnosis by
      computed tomography was difficult because of an artifact from the coils.
      Angiography, on the other hand, revealed a rupture of the aneurysm, and emergency
      surgery was performed. A Y-shaped graft was anastomosed to the ascending aorta
      under partial clamp. Then, one of its branches was anastomosed to the common
      carotid artery also under partial clamp in an end-to-side fashion. The cerebral
      blood flow monitored by a regional oximetry system (INVOS) remained stable. The
      other branch was anastomosed to the subclavian artery in end-to end fashion. No
      postoperative neurologic complications occurred. Angiography was useful in
      diagnosis of brachiocephalic artery aneurysm rupture after coil embolization.
      INVOS was also useful for monitoring the cerebral blood flow during surgery.

PMID- 27713205
TI  - [Reconstruction of Unilateral Absent Pulmonary Artery Using Ringed Prosthetic
      Graft;Report of a Case].
AB  - We have repaired a unilateral absent pulmonary artery(UAPA) using a prosthetic
      graft with a ring. Case 1 was a 1-month old girl. The right pulmonary artery(RPA)
      was anti-anatomically reconstructed with a 4 mm ePTFE graft. In postoperative
      year 1, however, the graft became stenosed due to compression by the ascending
      aorta. We reversed the stenosis with a 6 mm stent by percutaneous transluminal
      angioplasty. Case 2 was 6-year old boy. His RPA was anatomically reconstructed
      with a ringed 5 mm ePTFE graft when he was 5-months old. In postoperative year 6,
      he needed the graft exchanged because of the relatively decreased pulmonary flow
      due to body growth. Therefore, we exchanged the graft with an anti-anatomically
      ringed 12 mm ePTFE graft. No graft stenosis was observed during the perioperative
      course. Using a prosthetic graft with a ring may be a good solution to avoid
      compression from the ascending aorta.

PMID- 27713206
TI  - Bacterial Community Shift during the Startup of a Full-Scale Oxidation Ditch
      Treating Sewage.
AB  - The oxidation ditch (OD) is one of the most widely used processes for treating
      municipal wastewater. However, the microbial communities in the OD systems have
      not been well characterized, and little information about the shift of bacterial
      community during the startup process of the OD systems is available. In this
      study, we investigated the bacterial community changes during the startup period
      (over 100 days) of a full-scale OD. The results showed that the bacterial
      community dramatically changed during the startup period. Similar to the
      activated sludge samples in other studies, Proteobacteria (accounting for 26.3%
      48.4%) was the most dominant bacterial phylum in the OD system, but its relative
      abundance declined nearly 40% during the startup process. It was also found that
      Planctomycetes proliferated greatly (from 4.79% to 13.5%) and finally replaced
      Bacteroidetes as the second abundant phylum in the OD system. Specifically, some
      bacteria affiliated with genus Flavobacterium exhibited remarkable decreasing
      trends, whereas bacterial species belonging to the OD1 candidate division and
      Saprospiraceae family were found to increase during the startup process. Despite
      of the bacterial community shift, the organic matter, nitrogen, and phosphorus in
      the effluent were always in low concentrations, suggesting the functional
      redundancy of the bacterial community. Moreover, by comparing with the bacterial
      community in other municipal wastewater treatment bioreactors, some potentially
      novel bacterial species were found to be present in the OD system. Collectively,
      this study improved our understandings of the bacterial community structure and
      microbial ecology during the startup of a full-scale wastewater treatment
      bioreactor.

PMID- 27713207
TI  - Identification of a Bacillus thuringiensis Surface Layer Protein with Cytotoxic
      Activity against MDA-MB-231 Breast Cancer Cells.
AB  - In this work, we isolated a surface layer protein (SLP) from a Bacillus
      thuringiensis (Bt) strain to evaluate it cytotoxic effects against MDA-MB-231
      human breast cancer cells. AP11 was selected from a group of Bt strains using SLP
      oligonucleotides developed from Bacillus conserved regions. The AP11 strain was
      grown in Luria Bertani medium until the late exponential phase; an 86 kDa protein
      was extracted using 5 M LiCl and identified by liquid chromatography- tandem mass
      spectrometry. It corresponded to a multispecies SLP highly similar to previously
      described SLPs in Bt. The MDA-MB-231 breast cancer cells LC50 was obtained using
      0.25 MUg/ml of the isolated SLP. HaCat non-cancerous cells presented 90% survival
      using the same protein concentration. Our data suggest that SLP cytotoxicity
      against MDA-MB-231 could be induced by an interaction with the CDH11 cell
      membrane receptor.

PMID- 27713208
TI  - Antimicrobial Activity of Flaxseed Meal Extract against Escherichia coli O157:H7
      and Staphylococcus aureus Inoculated on Red Mustard.
AB  - This study examined the antimicrobial activity of flaxseed meal extract (FME)
      against Staphylococcus aureus and Escherichia coli O157:H7 inoculated on red
      mustard. With the treatment of 0.7% FME for 3 min, the reduction levels of S.
      aureus and E. coli O157:H7 populations were 1.23 and 1.83 log CFU/g,
      respectively. In addition, the combined treatment of 0.7% FME at 50 degrees C for
      3 min reduced the populations of the pathogenic bacteria by 2.28 and 2.41 log
      CFU/g, respectively. The color and the vitamin C content were not significantly
      different between treatments. Thus, FME can be used as a novel antimicrobial
      agent in freshcut vegetables.

PMID- 27713209
TI  - Virulence Factors and Stability of Coliphages Specific to Escherichia coli
      O157:H7 and to Various E. coli Infection.
AB  - Characteristics of E. coli O157:H7-specific infection bacteriophages (O157
      coliphages) and broad-host-range bacteriophages for other E. coli serotypes
      (broad-host coliphages) were compared. The burst sizes of the two groups ranged
      from 40 to 176 PFU/infected cell. Distributions of the virulence factors stx1,
      stx2, ehxA, and saa between the two groups were not differentiated. Broad-host
      range coliphages showed lower stability at 70 degrees C, in relation to O157
      coliphages. However, O157 coliphages showed high acid and ethanol tolerance by
      reduction of only 22% and 11% phages, respectively, under pH 3 and 70% ethanol
      for 1 h exposure. Therefore, these results revealed that the O157 coliphages
      might be more stable under harsh environments, which might explain their
      effective infection of the acid-tolerant E. coli O157:H7.

PMID- 27713210
TI  - Efficient (3R)-Acetoin Production from meso-2,3-Butanediol Using a New Whole-Cell
      Biocatalyst with Co-Expression of meso-2,3-Butanediol Dehydrogenase, NADH
      Oxidase, and Vitreoscilla Hemoglobin.
AB  - Acetoin (AC) is a volatile platform compound with various potential industrial
      applications. AC contains two stereoisomeric forms: (3S)-AC and (3R)-AC.
      Optically pure AC is an important potential intermediate and widely used as a
      precursor to synthesize novel optically active materials. In this study, chiral
      (3R)-AC production from meso-2,3-butanediol (meso-2,3-BD) was obtained using
      recombinant Escherichia coli cells co-expressing meso-2,3-butanediol
      dehydrogenase (meso-2,3-BDH), NADH oxidase (NOX), and hemoglobin protein (VHB)
      from Serratia sp. T241, Lactobacillus brevis, and Vitreoscilla, respectively. The
      new biocatalyst of E. coli/pET-mbdh-nox-vgb was developed and the bioconversion
      conditions were optimized. Under the optimal conditions, 86.74 g/l of (3R)-AC
      with the productivity of 3.61 g/l/h and the stereoisomeric purity of 97.89% was
      achieved from 93.73 g/l meso-2,3-BD using the whole-cell biocatalyst. The yield
      and productivity were new records for (3R)-AC production. The results exhibit the
      industrial potential for (3R)-AC production via whole-cell biocatalysis.

PMID- 27713211
TI  - Characterization of Interphase Microbial Community in Luzhou-Flavored Liquor
      Manufacturing Pits of Various Ages by Polyphasic Detection Methods.
AB  - It is vital to understand the changing characteristics of interphase microbial
      communities and interspecies synergism during the fermentation of Chinese
      liquors. In this study, microbial communities in the three indispensable phases
      (pit mud, zaopei, and huangshui) of Luzhou-flavored liquor manufacturing pits and
      their shifts during cellars use were first investigated by polyphasic culture
      independent approaches. The archaeal and eubacterial communities in the three
      phases were quantitatively assessed by combined phospholipid ether
      lipids/phospholipid fatty acid analysis and fluorescence in situ hybridization.
      In addition, qualitative information regarding the microbial community was
      analyzed by PCR-denaturing gradient gel electrophoresis. Results suggested that
      the interphase microbial community profiles were quite different, and the
      proportions of specific microbial groups evolved gradually. Anaerobic bacteria
      and gram-positive bacteria were dominant and their numbers were higher in pit mud
      (109 cells/g) than in huangshui (107 cells/ml) and zaopei (107cells/g).
      Hydrogenotrophic methanogenic archaea were the dominant archaea, and their
      proportions were virtually unchanged in pit mud (around 65%), whereas they first
      increased and then decreased in zaopei (59%-82%-47%) and increased with pit age
      in huangshui (82%-92%). Interactions between microbial communities, especially
      between eubacteria and methanogens, played a key role in the formation of
      favorable niches for liquor fermentation. Furthermore, daqu (an essential
      saccharifying and fermentative agent) and metabolic regulation parameters greatly
      affected the microbial community.

PMID- 27713212
TI  - Isolation, Identification, and Expression of Microbial Cellulases from the Gut of
      Odontotermes formosanus.
AB  - Termites are destructive to agriculture, forestry, and buildings, but they can
      also promote agro-ecosystem balance through the degradation of lignocellulose.
      Termite-triggered cellulose digestion may be clarified through microbial
      metabolism of cellulose products. In the present study, we characterized the
      activities of cellulase and its three components synthesized by the cellulase
      producing fungal strain HDZK-BYTF620 isolated from the gut of Odontotermes
      formosanus. The protein components of cellulases were synthesized by strain HDZK
      BYTF620, which were isolated and characterized using polyacrylamide gel
      electrophoresis, and the expression of the cellulases was studied at the proteome
      level.

PMID- 27713213
TI  - Identification of Uncommon Candida Species Using Commercial Identification
      Systems.
AB  - Recently, several studies have revealed that commercial microbial identification
      systems do not accurately identify the uncommon causative species of candidiasis,
      including Candida famata, Meyerozyma guilliermondii, and C. auris. We
      investigated the accuracy of species-level identification in a collection of
      clinical isolates previously identified as C. famata (N = 38), C. lusitaniae (N =
      1 2), and M. guilliermondii (N = 5) by the Vitek 2 system. All 55 isolates were
      re-analyzed by the Phoenix system (Becton Dickinson Diagnostics), two matrix
      assisted laser desorption ionization-time of flight mass spectrometry analyzers
      (a Vitek MS and a Bruker Biotyper), and by sequencing of internal transcribed
      spacer (ITS) regions or 26S rRNA gene D1/D2 domains. Among 38 isolates previously
      identified as C. famata by the Vitek 2 system, the majority (27/38 isolates,
      71.1%) were identified as C. tropicalis (20 isolates) or C. albicans (7 isolates)
      by ITS sequencing, and none was identified as C. famata. Among 20 isolates that
      were identified as C. tropicalis, 17 (85%) were isolated from urine. The two
      isolates that were identified as C. auris by ITS sequencing originated from ear
      discharge. The Phoenix system did not accurately identify C. lusitaniae, C.
      krusei, or C. auris. The correct identification rate for 55 isolates was 92.7%
      (51/55 isolates) for the Vitek MS and 94.6% (52/55 isolates) for the Bruker
      Biotyper, as compared with results from ITS sequencing. These results suggest
      that C. famata is very rare in Korea, and that the possibility of
      misidentification should be noted when an uncommon Candida species is identified.

PMID- 27713214
TI  - Trametes villosa Lignin Peroxidase (TvLiP): Genetic and Molecular
      Characterization.
AB  - White-rot basidiomycetes are the organisms that decompose lignin most
      efficiently, and Trametes villosa is a promising species for ligninolytic enzyme
      production. There are several publications on T. villosa applications for lignin
      degradation regarding the expression and secretion of laccase and manganese
      peroxidase (MnP) but no reports on the identification and characterization of
      lignin peroxidase (LiP), a relevant enzyme for the efficient breakdown of lignin.
      The object of this study was to identify and partially characterize, for the
      first time, gDNA, mRNA, and the corresponding lignin peroxidase (TvLiP) protein
      from T. villosa strain CCMB561 from the Brazilian semiarid region. The presence
      of ligninolytic enzymes produced by this strain grown in inducer media was
      qualitatively and quantitatively analyzed by spectrophotometry, qPCR, and dye
      fading using Remazol Brilliant Blue R. The spectrophotometric analysis showed
      that LiP activity was higher than that of MnP. The greatest LiP expression as
      measured by qPCR occurred on the 7th day, and the ABSA medium (agar, sugarcane
      bagasse, and ammonium sulfate) was the best that favored LiP expression. The
      amplification of the TvLiP gene median region covering approximately 50% of the
      T. versicolor LPGIV gene (87% identity); the presence of Trp199, Leu115, Asp193,
      Trp199, and Ala203 in the translated amplicon of the T. villosa mRNA; and the
      close phylogenetic relationship between TvLiP and T. versicolor LiP all indicate
      that the target enzyme is a lignin peroxidase. Therefore, T. villosa CCMB561 has
      great potential for use as a LiP, MnP, and Lac producer for industrial
      applications.

PMID- 27713215
TI  - Structural Analyses of Zinc Finger Domains for Specific Interactions with DNA.
AB  - Zinc finger proteins are among the most extensively applied metalloproteins in
      the field of biotechnology owing to their unique structural and functional
      aspects as transcriptional and translational regulators. The classical zinc
      fingers are the largest family of zinc proteins and they provide critical roles
      in physiological systems from prokaryotes to eukaryotes. Two cysteine and two
      histidine residues (Cys2His2) coordinate to the zinc ion for the structural
      functions to generate a betabetaalpha fold, and this secondary structure supports
      specific interactions with their binding partners, including DNA, RNA, lipids,
      proteins, and small molecules. In this account, the structural similarity and
      differences of well-known Cys2His2-type zinc fingers such as zinc interaction
      factor 268 (ZIF268), transcription factor IIIA (TFIIIA), GAGA, and Ros will be
      explained. These proteins perform their specific roles in species from archaea to
      eukaryotes and they show significant structural similarity; however, their
      aligned amino acids present low sequence homology. These zinc finger proteins
      have different numbers of domains for their structural roles to maintain
      biological progress through transcriptional regulations from exogenous stresses.
      The superimposed structures of these finger domains provide interesting details
      when these fingers are applied to specific gene binding and editing. The
      structural information in this study will aid in the selection of unique types of
      zinc finger applications in vivo and in vitro approaches, because biophysical
      backgrounds including complex structures and binding affinities aid in the
      protein design area.

PMID- 27713216
TI  - In Vivo Wound Healing Activity of Crocodile (Crocodylus siamensis) Hemoglobin and
      Evaluation of Antibacterial and Antioxidant Properties of Hemoglobin and
      Hemoglobin Hydrolysate.
AB  - The hydrolysis of proteins constitutes an invaluable tool, granting access to a
      variety of peptide fragments with potentially interesting biological properties.
      Therefore, a hemoglobin (Hb) hydrolysate of Crocodylus siamensis was generated by
      digestion under acidic conditions. The antibacterial and antioxidant activities
      of the Hb hydrolysate were assessed in comparison with intact Hb. A disc
      diffusion assay revealed that the Hb hydrolysate exhibited antibacterial activity
      against eight strains of gram-positive bacteria and showed a higher efficacy than
      intact Hb. Moreover, the antioxidant activity of intact Hb and its hydrolysate
      was evaluated using ABTS and DPPH radical scavenging assays. The Hb hydrolysate
      exhibited free radical scavenging rates of 6-32%, whereas intact Hb showed a
      slightly higher activity. In addition, non-toxicity to human erythrocytes was
      observed after treatment with quantities of Hb hydrolysate up to 10 MUg.
      Moreover, active fragmented Hb (P3) was obtained after purifying the Hb
      hydrolysate by reversed-phase HPLC. Scanning electron microscopy demonstrated the
      induction of bacterial cell membrane abnormalities after exposure to P3.
      Antibacterial and antioxidant activities play crucial roles for supporting the
      wound healing activity. Consequently, an in vivo mice excisional skin wound
      healing assay was carried out to investigate the effects of intact Hb treatment
      on wound healing in more detail. The results clearly demonstrate that intact Hb
      is capable of promoting 75% wound closure within 6 days. These findings imply
      that intact Hb of C. siamensis and its acid hydrolysate may serve as valuable
      precursors for food supplementary products benefitting human health.

PMID- 27713217
TI  - The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation
      with Pituitary Adenoma Recurrence.
AB  - BACKGROUND: The 2004 World Health Organization classification introduced atypical
      pituitary adenoma (aPA), which was equivocally defined as invasion with increased
      mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and
      extensive p53 immunoreactivity. However, aPAs that exhibit all of these features
      are rare and the predictive value for recurrence in pituitary adenomas (PAs)
      remains uncertain. Thus, we sought to characterize pathological features of PAs
      that correlated with recurrence. METHODS: One hundred and sixty-seven cases of
      surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St.
      Mary's Hospital. Among them, 28 cases were confirmed to be recurrent, based on
      pathologic or radiologic examination. The pathologic characteristics including
      mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to
      recurrence. RESULTS: Analysis of the pathologic features indicated that only Ki
      67 LI over 3% was significantly associated with tumor recurrence (p = .02). The
      cases with at least one pathologic feature showed significantly higher recurrence
      rates (p < .01). Analysis indicated that cases with two pathologic features, Ki
      67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly
      associated with tumor recurrence (p < .01). CONCLUSIONS: Based on these results,
      PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%),
      or extensive p53 immunoreactivity (>= 20%). Assessment of these features is
      recommended for PA diagnosis for more accurate prediction of recurrence.

PMID- 27713218
TI  - Resumed Publication of Pharmaceuticals in 2009.
AB  - After a five year hiatus, we are pleased to announce the resumption of
      publication of the MDPI journal Pharmaceuticals (ISSN 1424-8247). First launched
      in 2004, few suitable papers were submitted and only one was published [1],
      before our limited editorial resources at the time led us to temporarily
      discontinue publication. Several things have changed since then. First, there has
      been an explosive growth in the number of manuscripts submitted and published in
      MDPI's various current journals [2], whose topics clearly fall within the
      intended scope of Pharmaceuticals and we feel that these manuscripts merit a
      dedicated forum. Second, the expansion of MDPI, now with Editorial Offices and
      staff in Basel (Switzerland) and Beijing (China), allows us to provide
      Pharmaceuticals' authors with all the services they could desire and deserve: a
      simple manuscript submission process, rigorous peer review, quick revision
      turnaround, Open Access publication on a new and attractive platform and coverage
      by all the major abstracting services. In addition, a new Editorial Board
      comprised of noted academic and industry scientists has been set up for
      Pharmaceuticals. Finally, to better focus the subject matter published in
      Pharmaceuticals on molecular medicines, we have also set up a special section in
      International Journal of Molecular Sciences (IJMS, ISSN 1422-0067) for papers on
      nutraceuticals or chemopreventives. We look forward to receiving and publishing
      your papers and as always, we welcome your comments and suggestions. [...].

PMID- 27713219
TI  - Fractionation of Mastic Gum in Relation to Antimicrobial Activity.
AB  - Mastic gum is a viscous light-green liquid obtained from the bark of Pistacia
      lentiscus var. chia. which belongs to the Anacardiaceae family. The gum has been
      fractionated to investigate the antimicrobial activity of the whole gum and its
      fractions against various strains of Helicobacter pylori. The polymeric gum
      fraction was separated from the essential oil and the resin (trunk exudates
      without essential oil) to assess and compare the anti-H. pylori activity of the
      polymer fraction against lower molecular weight fractions, the gum itself and
      masticated gum. The polymer fraction was also oxidized and assessed for
      antimicrobial activity.

PMID- 27713220
TI  - Knowledge and Implementation of the New European Guide in the Management of
      Arterial Hypertension. The Cigema Survey.
AB  - Knowledge of guideline implementation pitfalls allows anticipation and solving of
      problems and may help to promote implementation. The aims of this study were: 1)
      to find out how much is known among medical professionals about the
      recommendations for the Management of Arterial Hypertension; 2) to study in depth
      the extent of implementation and 3) to evaluate the manner in which this guide
      will be applied to daily medical practice. The Delphi method was used for this
      work. The total estimated sample size was 2,250 physicians. The carefully
      selected experts answered questionnaires in two or more rounds. The final sample
      size was 2,475 physicians. Results of the study are detailed in the article.
      Among the resultsIt is noteworthy that the guide is viewed as needed among all
      those who have been interviewed and this agreement about its need is generalised
      and that the improvement in medical practice, together with individual treatment
      and cardiovascular risk stratification are viewed positively in opinions reached
      by consensus by the majority of physicians, regardless of whether they are
      specialists or general practitioners. The main results of this study emphasize
      the fact that physicians need a guideline for the management of hypertensive
      patients and that most of physicians agree with them. The new guidelines on
      arterial hypertension management are widely known among physicians and there
      appears to be a global agreement regarding the need for the implementation of the
      new recommendations.

PMID- 27713221
TI  - Antitumor Activity of Some Prenylated Xanthones.
AB  - Pyranoxanthones 6-8 were obtained by dehydrogenation of the respective
      dihydropyranoxanthones 3-5 with DDQ in dry dioxane. Two prenylated xanthones
      10,11 were obtained from the reaction of 1-hydroxyxanthone (9) with prenyl
      bromide in alkaline medium, or by condensation of xanthone 9 with isoprene in the
      presence of orthophosphoric acid. The structural elucidation of the two new
      compounds 6,11, as well as an update of data for the already described prenylated
      derivatives 7,8,10 were accomplished by IR, UV, HRMS and NMR (1H, 13C, HSQC and
      HMBC) techniques. The effect of the prenylated xanthone derivatives on the in
      vitro growth of human tumor cell lines MCF-7 (breast adenocarcinoma) and NCI-H460
      (non-small cell lung cancer) is also reported. Compounds 10 and 11 have been
      found to exhibit a moderate growth inhibitory activity against the MCF-7 cell
      line.

PMID- 27713222
TI  - Antihypertensive Drug and Inner Ear Perfusion: An Otologist's Point of View.
AB  - A number of labyrinthine disorders with sensorineural hearing loss, vertigo, and
      tinnitus are known to occur to young people without vascular risk factors, thus
      being classified as "idiopathic" in the absence of satisfactory explanations; in
      the last decade, this phenomenon has found a reliable explanation by the adverse
      effect of a sharp decrease of blood pressure values followed by an abnormal
      vasomotor regulation. This model may not only be applied to healthy subjects, but
      even had some confirmation in conditions possibly affecting hemodynamic changes,
      such as heart failure or treated hypertension. In particular, the results of a
      recent study on the impact of different antihypertensive therapies, which was
      analyzed by monitoring the onset or enhancement of tinnitus as a symptom of inner
      ear sufferance, unequivocally demonstrated an increased prevalence of tinnitus in
      subjects submitted to more "aggressive" treatments. This seems in agreement with
      recent observations about the model of fluid homeostasis of the inner ear, and
      suggests, when possible, to resort to treatments with modulatory effects in order
      to maintain a steady perfusion to the labyrinth thus protecting its function.

PMID- 27713223
TI  - Fusion of a Short HA2-Derived Peptide Sequence to Cell-Penetrating Peptides
      Improves Cytosolic Uptake, but Enhances Cytotoxic Activity.
AB  - Cell-penetrating peptides (CPP) have become a widely used tool for efficient
      cargo delivery into cells. However, one limiting fact is their uptake by
      endocytosis causing the enclosure of the CPP-cargo construct within endosomes.
      One often used method to enhance the outflow into the cytosol is the fusion of
      endosome-disruptive peptide or protein sequences to CPP. But, until now, no
      studies exist investigating the effects of the fusion peptide to the cellular
      distribution, structural arrangements and cytotoxic behaviour of the CPP. In this
      study, we attached a short modified sequence of hemagglutinin subunit HA2 to
      different CPP and analysed the biologic activity of the new designed peptides.
      Interestingly, we observed an increased cytosolic distribution but also highly
      toxic activities in the micromolar range against several cell lines. Structural
      analysis revealed that attachment of the fusion peptide had profound implications
      on the whole conformation of the peptide, which might be responsible for membrane
      interaction and endosome disruption.

PMID- 27713224
TI  - Hypertensive Emergency in Aortic Dissection and Thoracic Aortic Aneurysm-A Review
      of Management.
AB  - Over the last few decades, treatment for aortic dissection and thoracic aortic
      aneurysms has evolved significantly with improvement in outcomes. Treatment
      paradigms include medical, endovascular and surgical options. As aortic
      dissection presents as a hypertensive emergency, diligent control of BP is of
      utmost importance in order to reduce the progression of dissection with possible
      aortic branch malperfusion. Treatment should begin on arrival to the emergency
      department and continues in the intensive care unit, endovascular suite or the
      operating room. Novel antihypertensive medications with improved pharmacological
      profile and improved surgical techniques, have improved the prognosis of patients
      with aortic aneurysm and/or aortic dissection. Nevertheless, morbidity and
      mortality remain high and hypertensive emergency poses a significant challenge in
      aortic dissection and thoracic aortic aneurysms.

PMID- 27713225
TI  - A New Classification of Prodrugs: Regulatory Perspectives.
AB  - Many therapeutic agents are manufactured and administered in prodrug forms. In
      this paper, a new classification system for prodrugs is proposed to provide
      useful information about where in the body a prodrug is converted to the active
      drug. In this system, prodrugs are classified into Type I or Type II and the
      respective Subtypes IA, IB, IIA, IIB or IIC based on their sites of conversion
      into the final active drug form. For Type I prodrugs, conversion occurs
      intracellularly (e.g., antiviral nucleoside analogs, lipid-lowering statins),
      whereas conversion of Type II prodrugs occurs extracellularly, for examples in
      digestive fluids, systemic circulation or other extracellular body fluids (e.g.,
      etoposide phosphate, valganciclovir, fosamprenavir). Type IA prodrugs refer to
      those that are converted at the cellular targets of therapeutic actions, whereas
      Type IB prodrugs' conversion occurs in the primary metabolic tissues such as
      liver, gut, or lung. For Type II prodrugs, the conversion process could either
      take place extracellularly in the milieu of gastrointestinal fluids (Type IIA),
      in the systemic circulation and/or other systemic extracellular fluid
      compartments (Type IIB), or near therapeutical target cells (Type IIC). A prodrug
      may belong to multiple categories and be recognized as a Mixed-Type prodrug. For
      example a prodrug may be converted both in target cells and metabolic tissues
      such as liver (i.e., named as a Type IA/IB prodrug), or one converted in both GI
      fluids and systemic circulations (i.e., named as a Type IIA/IIB prodrug). The
      Mixed-Type compound can be further distinguished as a Parallel Mixed-Type or
      Sequential Mixed-Type prodrug depending on the conversion processes that proceed
      with, either in concurrent or in sequential steps. Because traditional analysis
      of drug actions has always been focused on the site of action and mode of action,
      the proposed classification of prodrugs based on cellular locations of conversion
      is in line with current thought processes of regulatory review and risk
      assessment of both prodrug and active drug. By gaining insights regarding the
      site of action through prodrug nomenclature, risk benefit evaluation can be made
      more efficiently because both information on kinetics and impact of tissues
      involved are adequately revealed through prodrug subtype designated. In
      conclusion, the new system of classification will add to existing knowledge of
      prodrug classifications, and will provide improved insight into the contributory
      roles of both prodrug and active drug in the product's efficacy and safety, and
      their risk-benefit assessment.

PMID- 27713226
TI  - Obsessive-Compulsive and Post Traumatic Avoidance Symptoms Influence the Response
      to Antihypertensive Therapy: Relevance in Uncontrolled Hypertension.
AB  - AIM: To investigate the association of uncontrolled hypertension with
      psychological factors associated with high cardiovascular morbidity and mortality
      (type D personality, depression, posttraumatic stress-related symptoms). METHODS:
      205 consecutive outpatient hypertensives completed three questionnaires
      evaluating Type D personality (DS 16), post traumatic symptoms (revised Impact of
      Events Scale), symptoms of anxiety, hostility, depression and obsessive
      compulsive traits (subscales of the Symptom Checklist). Uncontrolled hypertension
      was diagnosed when clinic sitting blood pressure was above 140/90 mmHg (130/80 in
      the presence of diabetes or nephropathy), despite reported adherence to treatment
      with at least three antihypertensive medications, including a diuretic. RESULTS:
      Uncontrolled hypertension (39%), was predicted by lower scores at Symptom
      Checklist obsessive-compulsive subscale and higher number of post traumatic
      avoidance symptoms, older age, diabetes, higher systolic pressure at first visit
      and longstanding hypertension. Type D personality correlated with depression,
      hostility, anxiety, compulsiveness, history of malignancy, and older age, but not
      with uncontrolled hypertension. CONCLUSIONS: Uncontrolled hypertension is
      associated with low obsessionality and avoidance symptoms, which reduce
      compliance to treatment. On the contrary, type D personality is not correlated
      with uncontrolled hypertension, as it includes compulsiveness, which improves
      compliance. A multidisciplinary approach to the hypertensive patient is mandatory
      to establish if the psychological profile affects compliance.

PMID- 27713228
TI  - Aliskiren: Just a New Drug for Few Selected Patients or an Innovative Molecule
      Predestinated to Replace Arbs and Ace-Inhibitors?
AB  - The renin-angiotensin-aldosterone system (RAAS) plays a dominant role in the
      pathophysiology of hypertension, diabetes mellitus, chronic kidney disease and
      chronic heart failure. Therefore, drugs that block key components of the RAAS
      such as ACE inhibitors (ACEI) and angiotensin receptor blockers (ARBs) have
      gained wide clinical use for these indications. Despite progress, the morbidity
      and mortality of patients treated with ACEI or ARBs remain high. Aliskiren
      (Tekturna, Rasilez) is the first orally active inhibitor of renin approved for
      clinical use as an antihypertensive agent. The development program has
      established that at the licensed doses of 150 mg and 300 mg. Aliskiren is
      effective either as monotherapy or in combination with drugs from the other major
      classes. In this review we analyze and review the information already gained with
      Aliskiren, raises questions regarding the advantages of DRIs as monotherapy
      compared to marketed ACEIs and ARBs, their potential added value in combination
      with other RAAS modulators and other still unproven benefits in relation to
      prorenin and renin receptor biology.

PMID- 27713229
TI  - Combination Therapy with Olmesartan and Amlodipine in the Treatment of
      Hypertension.
AB  - BACKGROUND: Combination therapy with antihypertensive agents utilises different
      mechanisms of action and may be responsible for a more effective decrease in
      blood pressure. OBJECTIVE: To review the recently published trials on efficacy
      and safety of the combination therapy with olmesartan and amlodipine. RESULTS:
      The double-blind American COACH (Combination of Olmesartan Medoxomil and
      Amlopdine Besylate in Controlling High Blood Pressure) study (2008) showed in
      1,940 patients that after eight weeks of treatment the BP goals were most
      frequently achieved in the 'combination therapy group', with 56.3% (54.1-58.5%)
      and 54.0% (51.8-56.2%) of patients reaching adequate blood pressure of.

PMID- 27713227
TI  - Functional Consequences of Mutations and Polymorphisms in the Coding Region of
      the PAF Acetylhydrolase (PAF-AH) Gene.
AB  - In the past several years a number of alterations in the PAFAH/PLA2G7/LpPLA2 gene
      have been described. These include inactivating mutations, polymorphisms in the
      coding region, and other genetic changes located in promoter and intronic regions
      of the gene. The consequences associated with these genetic variations have been
      evaluated from different perspectives, including in vitro biochemical and
      molecular studies and clinical analyses in human subjects. This review highlights
      the current state of the field and suggests new approaches that can be used to
      evaluate functional consequences associated with mutations and polymorphisms in
      the PAF-AH gene.

PMID- 27713230
TI  - Coenzyme Q10 and Neurological Diseases.
AB  - Coenzyme Q10 (CoQ10, or ubiquinone) is a small electron carrier of the
      mitochondrial respiratory chain with antioxidant properties. CoQ10
      supplementation has been widely used for mitochondrial disorders. The rationale
      for using CoQ10 is very powerful when this compound is primary decreased because
      of defective synthesis. Primary CoQ10 deficiency is a treatable condition, so
      heightened "clinical awareness" about this diagnosis is essential. CoQ10 and its
      analogue, idebenone, have also been widely used in the treatment of other
      neurodegenerative disorders. These compounds could potentially play a therapeutic
      role in Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis,
      Friedreich's ataxia, and other conditions which have been linked to mitochondrial
      dysfunction. This article reviews the physiological roles of CoQ10, as well as
      the rationale and the role in clinical practice of CoQ10 supplementation in
      different neurological diseases, from primary CoQ10 deficiency to
      neurodegenerative disorders.

PMID- 27713231
TI  - Oxytocin: Old Hormone, New Drug.
AB  - Oxytocin (OT), traditionally associated with reproductive functions, was
      revisited recently, and several new functions in cardiovascular regulation were
      discovered. These functions include stimulation of the cardioprotective mediators
      nitric oxide (NO) and atrial natriuretic peptide. OT's cardiovascular outcomes
      comprise: (i) natriuresis, (ii) blood pressure reduction, (iii) negative
      inotropic and chronotropic effects, (iv) parasympathetic neuromodulation, (v) NO
      pathway involvement in vasodilatation and endothelial cell growth, (vi) anti
      inflammatory and (vii) antioxidant activities as well as (viii) metabolic
      effects. In addition, we have reported abundant OT in the early developing heart
      with its capacity to generate cardiomyocytes (CMs) from mouse embryonic stem
      cells and stem cells residing in the heart. OT increases glucose uptake by
      cultured CMs, in normal, hypoxic and even in insulin resistance conditions. In
      experimentally-induced myocardial infarction in rats, continuous in vivo OT
      delivery improves the cardiac healing process and cardiac work, diminishes
      inflammation, and stimulates angiogenesis. Therefore, in pathological situations,
      OT plays an anti-inflammatory and cardioprotective role, enhancing vascular and
      metabolic functions, with potential therapeutic application(s).

PMID- 27713232
TI  - Effect of Different Metal Ions on the Biological Properties of Cefadroxil.
AB  - The effect of different metal ions on the intestinal transport and the
      antibacterial activity of cefadroxil [(6R,7R)-7-{[(2R)-2-amino-2-(4
      hydroxyphenyl)acetyl]amino}-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2
      carboxylic acid] was investigated. The [14C]Gly-Sar uptake via PEPT1 was
      inhibited by Zn2+ and Cu2+ treatment in a concentration-dependent manner (Ki
      values 107 +/- 23 and 19 +/- 5 MUM, respectively). Kinetic analysis showed that
      the Kt of Gly-Sar uptake was increased 2-fold in the presence of zinc sulphate
      (150 MUM) whereas the Vmax value were not affected suggesting that zinc ions
      inhibited Gly-Sar uptake by PEPT1 in a competitively manner. Ni2+ exhibited
      moderate inhibitory effect, whereas Co2+, Mg2+, Al3+ ions showed no inhibitory
      effect on Gly-Sar uptake via PEPT1. Subsequently, we examined the effect of Zn2+
      and Al3+ ions on the transepithelial transport of cefadroxil across Caco-2 cells
      cultured on permeable supports. The results showed that zinc ions inhibited the
      transepithelial flux of cefadroxil at Caco-2 cell monolayers while Al3+ ions had
      no effect. The interaction of cephalosporins with the metal ions could suggest
      negative effects of some metal ions on the clinical aspects of small intestinal
      peptide and drug transport. Finally, the effect of Zn2+, Cu2+ and Al3+ ions on
      the antibacterial activity of cefadroxil was tested. It was found that there is
      no significant difference between the activity of cefadroxil and the cefadroxil
      metal ion complexes studied against the investigated sensitive bacterial species.

PMID- 27713233
TI  - Resveratrol: An Antiaging Drug with Potential Therapeutic Applications in
      Treating Diseases.
AB  - The prevention of aging is one of the most fascinating areas in biomedicine. The
      first step in the development of effective drugs for aging prevention is a
      knowledge of the biochemical pathways responsible for the cellular aging process.
      In this context it seems clear that free radicals play a key role in the aging
      process. However, in recent years it has been demonstrated that the families of
      enzymes called sirtuins, specifically situin 1 (SIRT1), have an anti-aging
      action. Thus, the natural compound resveratrol is a natural compound that shows a
      very strong activation of SIRT1 and also shows antioxidant effects. By activating
      sirtuin 1, resveratrol modulates the activity of numerous proteins, including
      peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1 alpha), the
      FOXO family, Akt (protein kinase B) and NFkappabeta. In the present review, we
      suggest that resveratrol may constitute a potential drug for prevention of ageing
      and for the treatment of several diseases due to its antioxidant properties and
      sirtuin activation.

PMID- 27713234
TI  - Interferons as Therapy for Viral and Neoplastic Diseases: From Panacea to Pariah
      to Paragon.
AB  - For more than 20 years after the excitement engendered by their discovery in 1957
      as antiviral agents, there were no significant clinical uses of interferons;
      however, following their cloning they have been employed as effective treatment
      for several viral, autoimmune, and neoplastic diseases.

PMID- 27713235
TI  - The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure,
      Ameliorates Renal Injury and Improves Vascular Function in Hypertension.
AB  - Soluble epoxide hydrolase inhibitors (sEHIs) are demonstrating promise as
      potential pharmaceutical agents for the treatment of cardiovascular disease,
      diabetes, inflammation, and kidney disease. The present study determined the
      ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve
      vascular function, and decrease renal inflammation and injury in angiotensin
      hypertension. Rats were infused with angiotensin and AR9281 was given orally
      during the 14-day infusion period. Systolic blood pressure averaged 180 +/- 5
      mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure
      to 142 +/- 7 mmHg in angiotensin hypertension. Histological analysis demonstrated
      decreased injury to the juxtamedullary glomeruli. Renal expression of
      inflammatory genes was increased in angiotensin hypertension and two weeks of
      AR9281 treatment decreased this index of renal inflammation. Vascular function in
      angiotensin hypertension was also improved by AR9281 treatment. Decreased
      afferent arteriolar and mesenteric resistance endothelial dependent dilator
      responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats.
      These data demonstrate that the first-in-class sEHI, AR9281, lowers blood
      pressure, improves vascular function and reduces renal damage in angiotensin
      hypertension.

PMID- 27713236
TI  - Malaria-Infected Mice Are Cured by a Single Low Dose of a New Silylamide Trioxane
      Plus Mefloquine.
AB  - Three thermally and hydrolytically stable silylamide trioxanes have been prepared
      from the natural trioxane artemisinin in only five simple chemical steps and in
      at least 56% overall yield. Two of these new chemical entities completely cured
      malariainfected mice at a single oral dose of only 8 mg/kg combined with 24 mg/kg
      of mefloquine hydrochloride. The high efficacy of this ACT chemotherapy is
      considerably better than the efficacy using the popular trioxane drug artemether
      plus mefloquine hydrochloride.

PMID- 27713237
TI  - Real Time Imaging of Biomarkers in the Parkinson's Brain Using Mini-Implantable
      Biosensors. II. Pharmaceutical Therapy with Bromocriptine.
AB  - We used Neuromolecular Imaging (NMI) and trademarked BRODERICK PROBE(r) mini
      implantable biosensors, to selectively and separately detect neurotransmitters in
      vivo, on line, within seconds in the dorsal striatal brain of the Parkinson's
      Disease (PD) animal model. We directly compared our results derived from PD to
      the normal striatal brain of the non-Parkinson's Disease (non-PD) animal. This
      advanced biotechnology enabled the imaging of dopamine (DA), serotonin (5-HT),
      homovanillic acid (HVA) a metabolite of DA, L-tryptophan (L-TP) a precursor to 5
      HT and peptides, dynorphin A 1-17 (Dyn A) and somatostatin (somatostatin
      releasing inhibitory factor) (SRIF). Each neurotransmitter and neurochemical was
      imaged at a signature electroactive oxidation/half-wave potential in dorsal
      striatum of the PD as compared with the non-PD animal. Both endogenous and
      bromocriptine-treated neurochemical profiles in PD and non-PD were imaged using
      the same experimental paradigm and detection sensitivities. Results showed that
      we have found significant neurotransmitter peptide biomarkers in the dorsal
      striatal brain of endogenous and bromocriptine-treated PD animals. The peptide
      biomarkers were not imaged in dorsal striatal brain of non-PD animals, either
      endogenously or bromocriptine-treated. These findings provide new
      pharmacotherapeutic strategies for PD patients. Thus, our findings are highly
      applicable to the clinical treatment of PD.

PMID- 27713239
TI  - Spironolactone Plus Full-Dose ACE Inhibition in Patients with Idiopathic
      Membranous Nephropathy and Nephrotic Syndrome: Does It Really Work?
AB  - We have studied the effects of add-on spironolactone treatment (100 mg/day) in 11
      patients with idiopathic membranous nephropathy (IMN) and > 3 gm proteinuria/day
      despite angiotensin converting enzyme (ACE) inhibitor therapy titrated to a
      systolic/diastolic blood pressure < 120/80 mmHg. Blood pressure, 24-hour urinary
      protein excretion, and creatinine clearance were measured prior to, after two
      months of combined therapy, and after a 2-month withdrawal period of
      spironolactone. While systolic and diastolic blood pressure decreased
      significantly after spironolactone therapy, proteinuria did not improve. Serum
      potassium increased significantly as well, with three patients requiring resin
      binding therapy. Thus, spironolactone seems to have no additional antiproteinuric
      effects over ACE inhibitor therapy in patients with IMN and nephrotic syndrome
      and carries the risk of significant hyperkalemia.

PMID- 27713240
TI  - Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update.
AB  - After beta lactam antibiotics, hypersensitivity reactions to nonsteroidal
      antiinflammatory drugs are the second cause of hypersensitivity to drugs. Acute
      manifestations affect the respiratory tract (aspirin exacerbated respiratory
      disease), the skin (urticaria and angioedema), or are generalized (anaphylaxis).
      Correct diagnosis and treatment in order to prevent unnecessary morbidity and the
      potential risk of death from these severe reactions, and to provide proper
      medical advice on future drug use frequently requires the participation of
      allergology specialists familiar with these clinical conditions.

PMID- 27713242
TI  - Role of Glycogen Synthase Kinase-3beta in APP Hyperphosphorylation Induced by
      NMDA Stimulation in Cortical Neurons.
AB  - The phosphorylation of Amyloid Precursor Protein (APP) at Thr668 plays a key role
      in APP metabolism that is highly relevant to AD. The c-Jun-N-terminal kinase
      (JNK), glycogen synthase kinase-3beta (GSK-3beta) and cyclin-dependent kinase 5
      (Cdk5) can all be responsible for this phosphorylation. These kinases are
      activated by excitotoxic stimuli fundamental hallmarks of AD. The exposure of
      cortical neurons to a high dose of NMDA (100 MUM) for 30'-45' led to an increase
      of P-APP Thr668. During NMDA stimulation APP hyperphosphorylation has to be
      assigned to GSK-3beta activity, since addition of L803-mts, a substrate
      competitive inhibitor of GSK-3beta reduced APP phosphorylation induced by NMDA.
      On the contrary, inhibition of JNK and Cdk5 with D-JNKI1 and Roscovitine
      respectively did not prevent NMDA-induced P-APP increase. These data show a tight
      connection, in excitotoxic conditions, between APP metabolism and the GSK-3beta
      signaling pathway.

PMID- 27713241
TI  - The Timing of Antidepressant Effects: A Comparison of Diverse Pharmacological and
      Somatic Treatments.
AB  - Currently available antidepressants used to treat major depressive disorder (MDD)
      unfortunately often take weeks to months to achieve their full effects, commonly
      resulting in considerable morbidity and increased risk for suicidal behavior. Our
      lack of understanding of the precise cellular underpinnings of this illness and
      of the mechanism of action of existing effective pharmacological treatments is a
      large part of the reason that therapies with a more rapid onset of antidepressant
      action (ROAA) have not been developed. Other issues that need to be addressed
      include heterogeneous clinical concepts and statistical models to measure rapid
      antidepressant effects. This review describes the timing of onset of
      antidepressant effects for various therapies used to treat MDD. While several
      agents produce earlier improvement of depressive symptoms (defined as occurring
      within one week), the response rate associated with such agents can be quite
      variable. These agents include both currently available antidepressants as well
      as other pharmacological and non-pharmacological interventions. Considerably
      fewer treatments are associated with ROAA, defined as occurring within several
      hours or one day. Treatment strategies for MDD whose sustained antidepressant
      effects manifest within hours or even a few days would have an enormous impact on
      public health.

PMID- 27713244
TI  - Comparison of Functional Protein Transduction Domains Using the NEMO Binding
      Domain Peptide.
AB  - Protein transduction domains (PTDs), both naturally occurring and synthetic, have
      been extensively utilized for intracellular delivery of biologically active
      molecules both in vitro and in vivo. However, most comparisons of transduction
      efficiency have been performed using fluorescent markers. To compare efficiency
      of functional protein transduction, a peptide derived from IkB kinase beta
      (IKKbeta) that prevents formation of an active IKK complex was used as a
      biologically active cargo. This peptide, termed NEMO Binding Domain (NBD), is
      able to block activation of the transcriptional factor NF-kappaB by IKK, but not
      basal NF-kappaB activity. Our results demonstrate that Antp and Tat PTDs were
      most effective for delivery of NBD for inhibition of NF-kB activation compared to
      other PTD-NBD in both Hela and 293 cells, however, at higher concentrations (100
      uM), the Antp-NBD as well as the FGF-NBD peptide caused significant cellular
      toxicity. In contrast to the cell culture results, delivery of NBD using 8K
      (octalysine) and 6R (six arginine) were the most effect in blocking inflammation
      following local, footpad delivery in a KLH-induced DTH murine model of
      inflammatory arthritis. These results demonstrate differences between PTDs for
      delivery of a functional cargo between cell types.

PMID- 27713238
TI  - Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as
      Therapeutic Targets.
AB  - Insulin, besides its glucose lowering effects, is involved in the modulation of
      lifespan, aging and memory and learning processes. As the population ages,
      neurodegenerative disorders become epidemic and a connection between insulin
      signaling dysregulation, cognitive decline and dementia has been established.
      Mitochondria are intracellular organelles that despite playing a critical role in
      cellular metabolism are also one of the major sources of reactive oxygen species.
      Mitochondrial dysfunction, oxidative stress and neuroinflammation, hallmarks of
      neurodegeneration, can result from impaired insulin signaling. Insulin
      sensitizing drugs such as the thiazolidinediones are a new class of synthetic
      compounds that potentiate insulin action in the target tissues and act as
      specific agonists of the peroxisome proliferator-activated receptor gamma (PPAR
      gamma). Recently, several PPAR agonists have been proposed as novel and possible
      therapeutic agents for neurodegenerative disorders. Indeed, the literature shows
      that these agents are able to protect against mitochondrial dysfunction,
      oxidative damage, inflammation and apoptosis. This review discusses the role of
      mitochondria and insulin signaling in normal brain function and in
      neurodegeneration. Furthermore, the potential protective role of insulin and
      insulin sensitizers in Alzheimer's, Parkinson's and Huntington's diseases and
      amyotrophic lateral sclerosis will be also discussed.

PMID- 27713246
TI  - Impact of Glycosylation on Effector Functions of Therapeutic IgG.
AB  - Human IgG has only one conserved glycosylation site located in the Cgamma2 domain
      of the Fc region that accounts for the presence of two sugar moieties per IgG.
      These IgG sugar cores play a critical role in a number of IgG effector functions.
      In the present review, we describe the main characteristics of IgG Fc
      glycosylation and some abnormalities of serum IgG glycosylation. We also discuss
      how glycosylation impacts on monoclonal antibodies (mAbs) and IVIg effector
      functions and how these molecules can be engineered. Several therapeutic
      antibodies have now been engineered to be no- or low-fucose antibodies and are
      currently tested in clinical trials. They exhibit an increased binding to
      activating FcgammaRIIIA and trigger a strong antibody-dependent cell cytotoxicity
      (ADCC) as compared to their highly-fucosylated counterparts. They represent a new
      generation of therapeutic antibodies that are likely to show a better clinical
      efficacy in patients, notably in cancer patients where cytotoxic antibodies are
      needed.

PMID- 27713245
TI  - Approved and Off-Label Uses of Obesity Medications, and Potential New
      Pharmacologic Treatment Options.
AB  - Available anti-obesity pharmacotherapy options remain very limited and
      development of more effective drugs has become a priority. The potential
      strategies to achieve weight loss are to reduce energy intake by stimulating
      anorexigenic signals or by blocking orexigenic signals, and to increase energy
      expenditure. This review will focus on approved obesity medications, as well as
      potential new pharmacologic treatment options.

PMID- 27713249
TI  - A New Baroreceptor Sensitivity-Restoring Ca-Channel Blocker Diminishes Age
      Related Morning Blood Pressure Increase in Hypertensive Patients: Open-Label
      Monitoring of Azelnidipine Treatment for Hypertension in the Early Morning (At
      HOME) Study.
AB  - BACKGROUND: Morning blood pressure (BP) surge, which exhibits an age-related
      increase, is a risk factor for stroke in elderly hypertensive patients,
      independently of the 24-h BP level. We studied the effect of the new baroreceptor
      sensitivity (BRS)-restoring Ca-channel blocker (CCB) azelnidipine (AZ) on this
      age-related morning BP increase. METHODS: We conducted a 16-week prospective
      study to clarify the effect of morning dosing of AZ on home BPs measured in the
      morning and in the evening in 2,546 hypertensive patients (mean age, 65.1 years;
      female, 53.6%). RESULTS: At baseline, ME-Dif (morning systolic BP [SBP]-evening
      SBP) increased with age, independently of ME-Ave (average of the morning and
      evening SBPs). This age-related increase of ME-Dif was exaggerated by regular
      alcohol drinking and beta-blocker use. After AZ treatment (14.3 +/- 3.6 mg/day),
      ME-AV and ME-Dif were significantly reduced independently of each other, with
      reductions of -18.1 +/- 15.6 and -2.5 +/- 13.2 mmHg, respectively (both p <
      0.001). AZ treatment decreased age-related increase in ME-Dif particularly in
      patients who were regular consumers of alcohol and in beta-blocker users.
      CONCLUSIONS: The new BRS-restoring CCB AZ significantly reduced age-related
      increase in morning BP and had some potential benefit on cardiovascular
      protection in hypertension, particularly in elderly patients and/or consumers of
      alcohol.

PMID- 27713243
TI  - A Novel Category of Anti-Hypertensive Drugs for Treating Salt-Sensitive
      Hypertension on the Basis of a New Development Concept.
AB  - Terrestrial animals must conserve water and NaCl to survive dry environments. The
      kidney reabsorbs 95% of the sodium filtered from the glomeruli before sodium
      reaches the distal connecting tubules. Excess sodium intake requires the renal
      kallikrein-kinin system for additional excretion. Renal kallikrein is secreted
      from the distal connecting tubule cells of the kidney, and its substrates, low
      molecular kininogen, from the principal cells of the cortical collecting ducts
      (CD). Formed kinins inhibit reabsorption of NaCl through bradykinin (BK)-B2
      receptors, localized along the CD. Degradation pathway of BK by kinin-destroying
      enzymes in urine differs completely from that in plasma, so that ACE inhibitors
      are ineffective. Urinary BK is destroyed mainly by a carboxypeptidase-Y-like
      exopeptidase (CPY) and partly by a neutral endopeptidase (NEP). Inhibitors of CPY
      and NEP, ebelactone B and poststatin, respectively, were found. Renal kallikrein
      secretion is accelerated by potassium and ATP-sensitive potassium (KATP) channel
      blockers, such as PNU-37883A. Ebelactone B prevents DOCA-salt hypertension in
      rats. Only high salt intake causes hypertension in animals deficient in BK-B2
      receptors, tissue kallikrein, or kininogen. Hypertensive patients, and
      spontaneously hypertensive rats, excrete less kallikrein than normal subjects,
      irrespective of races, and become salt-sensitive. Ebelactone B, poststatin, and
      KATP channel blockers could become novel antihypertensive drugs by increase in
      urinary kinin levels. Roles of kinin in cardiovascular diseases were discussed.

PMID- 27713248
TI  - Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms
      Associated with Their Stress-Protective Activity.
AB  - Adaptogens were initially defined as substances that enhance the "state of
      nonspecific resistance" in stress, a physiological condition that is linked with
      various disorders of the neuroendocrine-immune system. Studies on animals and
      isolated neuronal cells have revealed that adaptogens exhibit neuroprotective,
      anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity.
      In addition, a number of clinical trials demonstrate that adaptogens exert an
      anti-fatigue effect that increases mental work capacity against a background of
      stress and fatigue, particularly in tolerance to mental exhaustion and enhanced
      attention. Indeed, recent pharmacological studies of a number of adaptogens have
      provided a rationale for these effects also at the molecular level. It was
      discovered that the stress-protective activity of adaptogens was associated with
      regulation of homeostasis via several mechanisms of action, which was linked with
      the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of
      stress response, such as molecular chaperons (e.g., HSP70), stress-activated c
      Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription
      factor DAF-16, cortisol and nitric oxide.

PMID- 27713247
TI  - Oxidative Stress Induced Mitochondrial Failure and Vascular Hypoperfusion as a
      Key Initiator for the Development of Alzheimer Disease.
AB  - Mitochondrial dysfunction may be a principal underlying event in aging, including
      age-associated brain degeneration. Mitochondria provide energy for basic
      metabolic processes. Their decay with age impairs cellular metabolism and leads
      to a decline of cellular function. Alzheimer disease (AD) and cerebrovascular
      accidents (CVAs) are two leading causes of age-related dementia. Increasing
      evidence strongly supports the theory that oxidative stress, largely due to
      reactive oxygen species (ROS), induces mitochondrial damage, which arises from
      chronic hypoperfusion and is primarily responsible for the pathogenesis that
      underlies both disease processes. Mitochondrial membrane potential, respiratory
      control ratios and cellular oxygen consumption decline with age and correlate
      with increased oxidant production. The sustained hypoperfusion and oxidative
      stress in brain tissues can stimulate the expression of nitric oxide synthases
      (NOSs) and brain endothelium probably increase the accumulation of oxidative
      stress products, which therefore contributes to blood brain barrier (BBB)
      breakdown and brain parenchymal cell damage. Determining the mechanisms behind
      these imbalances may provide crucial information in the development of new, more
      effective therapies for stroke and AD patients in the near future.

PMID- 27713250
TI  - Quercetin: A Treatment for Hypertension?-A Review of Efficacy and Mechanisms.
AB  - Quercetin is a polyphenolic flavonoid. Common sources in the diet are apples,
      onions, berries, and red wine. Epidemiological studies have found an inverse
      relationship between dietary quercetin intake and cardiovascular disease. This
      has led to in vitro, in vivo, and clinical research to determine the mechanism by
      which quercetin exerts cardioprotective effects. Recent studies have found a
      reduction in blood pressure when hypertensive (>140 mm Hg systolic and >90 mm Hg
      diastolic) animals and humans are supplemented with quercetin. Proposed
      mechanisms for the antihypertensive effect of quercetin include decreased
      oxidative stress, inhibition of angiotensin converting enzyme activity, improved
      endothelial function, direct action on the vascular smooth muscle, and/or
      modulation in cell signaling and gene expression. Although in vitro and in vivo
      evidence exists to support and refute each possibility, it is likely that
      quercetin influences multiple targets via a combination of known and as yet
      undiscovered mechanisms. The purpose of this review is to examine the mechanisms
      whereby quercetin might reduce blood pressure in hypertensive individuals.

PMID- 27713251
TI  - Antihypertensive Peptides from Milk Proteins.
AB  - Dietary proteins possess a wide range of nutritional and functional properties.
      They are used as a source of energy and amino acids, which are needed for growth
      and development. Many dietary proteins, especially milk proteins, contain
      physiologically active peptides encrypted in the protein sequence. These peptides
      may be released during gastrointestinal digestion or food processing and once
      liberated, cause different physiological functions. Milk-derived bioactive
      peptides are shown to have antihypertensive, antimicrobial, immunomodulatory,
      antioxidative and mineral-binding properties. During the fermentation of milk
      with certain lactobacilli, two interesting tripeptides Ile-Pro-Pro and Val-Pro
      Pro are released from casein to the final product. These lactotripeptides have
      attenuated the development of hypertension in several animal models and lowered
      blood pressure in clinical studies. They inhibit ACE in vitro at micromolar
      concentrations, protect endothelial function in vitro and reduce arterial
      stiffness in humans. Thus, milk as a traditional food product can after certain
      processing serve as a functional food and carry specific health-promoting
      effects, providing an option to control blood pressure.

PMID- 27713252
TI  - Monoclonal Antibodies for Systemic Lupus Erythematosus (SLE).
AB  - A number of monoclonal antibodies (mAb) are now under investigation in clinical
      trials to assess their potential role in Systemic Lupus Erythematosus (SLE). The
      most frequently used mAb is rituximab, which is directed against CD20, a membrane
      protein expressed on B lymphocytes. Uncontrolled trials reported an improvement
      of SLE activity in non-renal patients and other studies even reported an
      improvement of severe lupus nephritis unresponsive to conventional treatments.
      However two randomized trials failed to show the superiority of rituximab over
      conventional treatment in non renal SLE and in lupus nephritis. Preliminary
      trials reported promising results with epratuzumab, a humanized mAb directed
      against CD22, and with belimumab, a human mAb that specifically recognizes and
      inhibits the biological activity of BLyS a cytokine of the tumornecrosis-factor
      (TNF) ligand superfamily. Other clinical trials with mAb directed against TNF
      alpha, interleukin-10 (Il-10), Il-6, CD154, CD40 ligand, IL-18 or complement
      component C5 are under way. At present, however, in spite of good results
      reported by some studies, no firm conclusion on the risk-benefit profile of these
      mAbs in patients with SLE can be drawn from the available studies.

PMID- 27713256
TI  - Structural Examination of 6-Methylsulphonylphenanthro- [9,10-C]-furan-1(3H)-one-A
      Rofecoxib Degradation Product.
AB  - In the attempt to discover a new polymorph of rofecoxib (Vioxx(r)), an unexpected
      product resulted. The product was characterised by chemical composition, thermal
      behaviour and structure and found to be 6-methylsulphonylphenanthro-[9,10-C]
      furan-1(3H)-one, a photo-cyclization degradation product of rofecoxib. This is a
      significant finding because it indicates that without appropriate control of the
      recrystallisation procedures, the structural integrity of rofecoxib may be
      seriously compromised.

PMID- 27713254
TI  - Oromucosal Administration of Interferon to Humans.
AB  - The prevailing dogma is that, to be systemically effective, interferon-alpha
      (IFNalpha) must be administered in sufficiently high doses to yield functional
      blood concentrations. Such an approach to IFNa therapy has proven effective in
      some instances, but high-dose parenteral IFNalpha therapy has the disadvantage of
      causing significant adverse events. Mounting evidence suggests that IFNalpha
      delivered into the oral cavity in low doses interacts with the oral mucosa in a
      unique manner to induce systemic host defense mechanisms without IFNalpha
      actually entering the circulation, thus reducing the potential for toxic side
      effects. A better understanding of the applications and potential benefits of
      this treatment modality are under active investigation. This paper provides a
      review of the relevant literature on the clinical use of the oromucosal route of
      administration of interferon, with an emphasis on the treatment of influenza.

PMID- 27713255
TI  - Olesoxime (TRO19622): A Novel Mitochondrial-Targeted Neuroprotective Compound.
AB  - Olesoxime (TRO19622) is a novel mitochondrial-targeted neuroprotective compound
      undergoing a pivotal clinical efficacy study in Amyotrophic Lateral Sclerosis
      (ALS) and also in development for Spinal Muscular Atrophy (SMA). It belongs to a
      new family of cholesterol-oximes identified for its survival-promoting activity
      on purified motor neurons deprived of neurotrophic factors. Olesoxime targets
      proteins of the outer mitochondrial membrane, concentrates at the mitochondria
      and prevents permeability transition pore opening mediated by, among other
      things, oxidative stress. Olesoxime has been shown to exert a potent
      neuroprotective effect in various in vitro and in vivo models. In particular
      olesoxime provided significant protection in experimental animal models of motor
      neuron disorders and more particularly ALS. Olesoxime is orally active, crosses
      the blood brain barrier, and is well tolerated. Collectively, its pharmacological
      properties designate olesoxime as a promising drug candidate for motor neuron
      diseases.

PMID- 27713253
TI  - Nitric Oxide Synthase Inhibitors as Antidepressants.
AB  - Affective and anxiety disorders are widely distributed disorders with severe
      social and economic effects. Evidence is emphatic that effective treatment helps
      to restore function and quality of life. Due to the action of most modern
      antidepressant drugs, serotonergic mechanisms have traditionally been suggested
      to play major roles in the pathophysiology of mood and stress-related disorders.
      However, a few clinical and several pre-clinical studies, strongly suggest
      involvement of the nitric oxide (NO) signaling pathway in these disorders.
      Moreover, several of the conventional neurotransmitters, including serotonin,
      glutamate and GABA, are intimately regulated by NO, and distinct classes of
      antidepressants have been found to modulate the hippocampal NO level in vivo. The
      NO system is therefore a potential target for antidepressant and anxiolytic drug
      action in acute therapy as well as in prophylaxis. This paper reviews the effect
      of drugs modulating NO synthesis in anxiety and depression.

PMID- 27713257
TI  - Cell Permeable Peptides: A Promising Tool to Deliver Neuroprotective Agents in
      the Brain.
AB  - The inability of most drugs to cross the blood-brain barrier and/or plasma
      membrane limits their use for biomedical applications in the brain. Cell
      Permeable Peptides (CPPs) overcome this problem and are effective in vivo,
      crossing the plasma membrane and the blood-brain barrier. CPPs deliver a wide
      variety of compounds intracellularly in an active form. In fact, many bioactive
      cargoes have neuroprotective properties, and due to their ability to block
      protein-protein interactions, offer exciting perspectives in the clinical
      setting. In this review we give an overview of the Cell Permeable Peptides
      strategy to deliver neuroprotectants against neurodegeneration in the CNS.

PMID- 27713258
TI  - Renal Side Effects of Non-Steroidal Anti-Inflammatory Drugs in Neonates.
AB  - Non-steroidal anti-inflammatory drugs like ibuprofen or indomethacin are commonly
      prescribed drugs to induce pharmacologic closure of a patent ductus arteriosus in
      preterm neonates. Based on a recently published Cochrane meta-analysis, both
      drugs are equally effective to induce closure. Drug choice can therefore be based
      on differences in side effects or pharmaco-economic arguments. The current review
      quantifies the negative impact of either ibuprofen or indomethacin on renal
      function, including diuresis, glomerular filtration rate and renal tubular
      function. Both ibuprofen and indomethacin have a quantifiable impact on renal
      function. However, compared to ibuprofen, the negative impact of indomethacin is
      more pronounced.

PMID- 27713259
TI  - Deregulation of Interferon Signaling in Malignant Cells.
AB  - Interferons (IFNs) are a family of cytokines with potent antiproliferative,
      antiviral, and immunomodulatory properties. Much has been learned about IFNs and
      IFN-activated signaling cascades over the last 50 years. Due to their potent
      antitumor effects in vitro and in vivo, recombinant IFNs have been used
      extensively over the years, alone or in combination with other drugs, for the
      treatment of various malignancies. This review summarizes the current knowledge
      on IFN signaling components and pathways that are deregulated in human
      malignancies. The relevance of deregulation of IFN signaling pathways in
      defective innate immune surveillance and tumorigenesis are discussed.

PMID- 27713260
TI  - Home and Office Blood Pressure Control among Treated Hypertensive Patients in
      Japan: Findings from the Japan Home versus Office Blood Pressure Measurement
      Evaluation (J-HOME) Study.
AB  - Appropriate control of blood pressure (BP) is essential for prevention of future
      cardiovascular events. However, BP control among treated hypertensive patients
      has been insufficient. Recently, the usefulness of self-measured BP at home (home
      BP measurement) for the management of hypertension has been reported in many
      studies. We evaluated BP control both at home and in the office among treated
      hypertensive patients in primary care settings in Japan (the J-HOME study). We
      found poor control of home and office BPs and clarified some factors affecting
      control. We also examined factors associated with the magnitude of the white-coat
      effect, the morning-evening BP difference, and home heart rate in this J-HOME
      study.

PMID- 27713262
TI  - Degradation of Methyldopa by Banana.
AB  - Methyldopa, an antihypertensive, is a very close analogue of DOPA. Drug
      interaction accompanied by degradation in a banana juice mixture was reported for
      DOPA. However, the effect of banana on methyldopa has not been reported.
      Therefore, we have investigated the impact of banana juice on methyldopa. The
      drug and supernatant of banana pulp were mixed, and the mixture was observed for
      changes in color, drug concentration, and ultraviolet-visible absorption spectra
      at 30  degrees C. The originally clear and colorless mixture started to acquire a
      yellow coloration after about 30 seconds after the mixing. The color tone
      increasingly deepened, then blistered solid particles that do not dissolve were
      observed after 3 hours. Concentration of methyldopa in the mixture decreased by
      60% after 5 min, to 0.5% after 30 min of the mixing. From these findings, it was
      suggested that the drastic alterations were caused by banana polyphenol oxidase
      that plays a role in the biosynthesis of melanin pigment from levodopa in banana
      pulp. Because the degradation of methyldopa occurs extremely fast, it was
      suggested concomitant use of this anti-hypertensive and banana juice consumption
      should be avoided in clinical practice.

PMID- 27713261
TI  - The Vasohibin Family.
AB  - Angiogenesis is regulated by the local balance between angiogenesis stimulators
      and inhibitors. A number of endogenous angiogenesis inhibitors have been found in
      the body. The origin of these inhibitors is mostly extrinsic to the vasculature.
      Recently, however, vascular endothelial cells themselves have been found to
      produce angiogenesis inhibitors including vasohibin-1. These intrinsic inhibitors
      are thought to regulate angiogenesis by an auto-regulatory or negative-feedback
      mechanism. This review will focus on vasohibin-1 produced by vascular endothelial
      cells and on its homologue, vasohibin-2.

PMID- 27713263
TI  - Cell-Penetrating Peptides for Antiviral Drug Development.
AB  - Viral diseases affect hundreds of millions of people worldwide, and the few
      available drugs to treat these diseases often come with limitations. The key
      obstacle to the development of new antiviral agents is their delivery into
      infected cells in vivo. Cell-penetrating peptides (CPPs) are short peptides that
      can cross the cellular lipid bilayer with the remarkable capability to shuttle
      conjugated cargoes into cells. CPPs have been successfully utilized to enhance
      the cellular uptake and intracellular trafficking of antiviral molecules, and
      thereby increase the inhibitory activity of potential antiviral proteins and
      oligonucleotide analogues, both in cultured cells and in animal models. This
      review will address the notable findings of these studies, highlighting some
      promising results and discussing the challenges CPP technology has to overcome
      for further clinical applications.

PMID- 27713264
TI  - Generic Medicine Pricing Policies in Europe: Current Status and Impact.
AB  - Generic medicine pricing is an area of national responsibility of European Union
      countries. This article aims to present the current status and impact of generic
      medicine pricing policies in ambulatory care in Europe. The study conducts a
      literature review of policies relating to free-pricing systems, price-regulated
      systems, price differentiation, price competition and discounts, and tendering
      procedures; and a survey of European generic medicine pricing policies.
      Competition from Indian generic medicine manufacturers, European variation in
      generic medicine prices and competition between generic medicine manufacturers by
      discount suggest that the potential savings to health care payers and patients
      from generic medicines are not fully realized in Europe. One way of attaining
      these savings may be to move away from competition by discount to competition by
      price. Free-pricing systems may drive medicine prices downwards under specific
      conditions. In price-regulated systems, regulation may lower prices of originator
      and generic medicines, but may also remove incentives for additional price
      reductions beyond those imposed by regulation. To date, little is known about the
      current status and impact of tendering procedures for medicines in ambulatory
      care. In conclusion, the European experience suggests that there is not a single
      approach towards developing generic medicine pricing policies in Europe.

PMID- 27713267
TI  - Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights
      from the Structure.
AB  - Plasma platelet-activating factor acetylhydrolase (PAF-AH), also called
      lipoprotein-associated phospholipase A2 (Lp-PLA2), is a group VIIA PLA2 enzyme
      that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although
      the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated,
      several studies have shown it to be an independent marker of cardiovascular
      diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller
      portion to HDL; the majority of the enzyme being associated with small dense LDL
      and VHDL-1 subclasses. Several studies suggest that the anti- or pro
      atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein
      it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL
      and HDL have been identified. However our understanding of the interaction of PAF
      AH with LDL and HDL is still incomplete. In this review we present an overview of
      what is already known about the interaction of PAF-AH with lipoprotein particles,
      and we pose questions that are yet to be answered. The recently solved crystal
      structure of PAF-AH, along with functional work done by others is used as a guide
      to develop a model of interaction of PAF-AH with lipoprotein particles.

PMID- 27713266
TI  - Inhaled Corticosteroids.
AB  - Inhaled corticosteroids (ICS) are the most effective controllers of asthma. They
      suppress inflammation mainly by switching off multiple activated inflammatory
      genes through reversing histone acetylation via the recruitment of histone
      deacetylase 2 (HDAC2). Through suppression of airway inflammation ICS reduce
      airway hyperresponsiveness and control asthma symptoms. ICS are now first-line
      therapy for all patients with persistent asthma, controlling asthma symptoms and
      preventing exacerbations. Inhaled long-acting beta2-agonists added to ICS further
      improve asthma control and are commonly given as combination inhalers, which
      improve compliance and control asthma at lower doses of corticosteroids. By
      contrast, ICS provide much less clinical benefit in COPD and the inflammation is
      resistant to the action of corticosteroids. This appears to be due to a reduction
      in HDAC2 activity and expression as a result of oxidative stress. ICS are added
      to bronchodilators in patients with severe COPD to reduce exacerbations. ICS,
      which are absorbed from the lungs into the systemic circulation, have negligible
      systemic side effects at the doses most patients require, although the high doses
      used in COPD has some systemic side effects and increases the risk of developing
      pneumonia.

PMID- 27713268
TI  - NSAIDs and Acute Pancreatitis: A Systematic Review.
AB  - The resulting pain is the main symptom of acute pancreatitis and it should be
      alleviated as soon as possible. NSAIDs are the first line therapy for pain and
      they are generally administered to acute pancreatitis patients upon admission to
      the hospital. In addition, these drugs have also been used to prevent post
      endoscopic cholangiopancreatography (ERCP) acute pancreatitis. On the other hand,
      there are several reports indicating that NSAIDs may be the actual cause of acute
      pancreatitis. We carried out a literature search on PubMed/MEDLINE; all full text
      papers published in from January 1966 to November 2009 on the use of NSAIDs in
      acute pancreatitis were collected; the literature search was also supplemented by
      a review of the bibliographies of the papers evaluated. Thus, in this article, we
      will systematically review the current literature in order to better illustrate
      the role of NSAIDs in acute pancreatitis, in particular: i) NSAIDs as a cause of
      acute pancreatitis; ii) their use to prevent post-retrograde ERCP pancreatitis
      and iii) their efficacy for pain relief in the acute illness of the pancreas.

PMID- 27713271
TI  - Distribution of CPP-Protein Complexes in Freshly Resected Human Tissue Material.
AB  - Interest in cell-penetrating peptides (CPPs) as delivery agents has fuelled a
      large number of studies conducted on cultured cells and in mice. However, only a
      few studies have been devoted to the behaviour of CPPs in human tissues.
      Therefore, we performed ex vivo tissue-dipping experiments where we studied the
      distribution of CPP-protein complexes in samples of freshly harvested human
      tissue material. We used the carcinoma or hyperplasia-containing specimens of the
      uterus and the cervix, obtained as surgical waste from nine hysterectomies. Our
      aim was to evaluate the tissue of preference (epithelial versus
      muscular/connective tissue, carcinoma versus adjacent histologically normal
      tissue) for two well-studied CPPs, the transportan and the TAT-peptide. We
      complexed biotinylated CPPs with avidin-?-galactosidase (ABG), which enabled us
      to apply whole-mount X-gal staining as a robust detection method. Our results
      demonstrate that both peptides enhanced the tissue distribution of ABG. The
      enhancing effect of the tested CPPs was more obvious in the normal tissue and in
      some specimens we detected a striking selectivity of CPP-ABG complexes for the
      normal tissue. This unexpected finding encourages the evaluation of CPPs as local
      delivery agents in non-malignant situations, for example in the intrauterine gene
      therapy of benign gynaecological diseases.

PMID- 27713270
TI  - Targeting the Tumour: Cell Penetrating Peptides for Molecular Imaging and
      Radiotherapy.
AB  - Over the last couple of years, the number of original papers and reviews
      discussing various applications of cell penetrating peptides (CPPs) has grown
      exponentially. This is not remarkable since CPPs are capable of transporting the
      most varying cargo across cell membranes which is one of the biggest problems in
      drug delivery and targeted therapy. In this review, we focus on the use of CPPs
      and related peptides for delivery of imaging contrast agents and radionuclides to
      cells and tissues with the ultimate goal of in vivo molecular imaging and
      molecular radiotherapy of intracellular and even intranuclear targets.

PMID- 27713269
TI  - Platelet-Derived Growth Factor (PDGF)/PDGF Receptors (PDGFR) Axis as Target for
      Antitumor and Antiangiogenic Therapy.
AB  - Angiogenesis in normal and pathological conditions is a multi-step process
      governed by positive and negative endogenous regulators. Many growth factors are
      involved in different steps of angiogenesis, like vascular endothelial growth
      factors (VEGF), fibroblast growth factor (FGF)-2 or platelet-derived growth
      factors (PDGF). From these, VEGF and FGF-2 were extensively investigated and it
      was shown that they significantly contribute to the induction and progression of
      angiogenesis. A lot of evidence has been accumulated in last 10 years that
      supports the contribution of PDGF/PDGFR axis in developing angiogenesis in both
      normal and tumoral conditions. The crucial role of PDGF-B and PDGFR-beta in
      angiogenesis has been demonstrated by gene targeting experiments, and their
      expression correlates with increased vascularity and maturation of the vascular
      wall. PDGF and their receptors were identified in a large variety of human tumor
      cells. In experimental models it was shown that inhibition of PDGF reduces
      interstitial fluid pressure in tumors and enhances the effect of chemotherapy.
      PDGFR have been involved in the cardiovascular development and their loss leads
      to a disruption in yolk sac blood vessels development. PDGFRbeta expression by
      pericytes is necessary for their recruitment and integration in the wall of tumor
      vessels. Endothelial cells of tumor-associated blood vessels can express PDGFR.
      Based on these data, it was suggested the potential benefit of targeting PDGFR in
      the treatment of solid tumors. The molecular mechanisms of PDGF/PDGFR-mediated
      angiogenesis are not fully understood, but it was shown that tyrosine kinase
      inhibitors reduce tumor growth and angiogenesis in experimental xenograft models,
      and recent data demonstrated their efficacy in chemoresistant tumors. The in vivo
      effects of PDGFR inhibitors are more complex, based on the cross-talk with other
      angiogenic factors. In this review, we summarize data regarding the mechanisms
      and significance of PDGF/PDGFR expression in normal conditions and tumors,
      focusing on this axis as a potential target for antitumor and antiangiogenic
      therapy.

PMID- 27713265
TI  - The Chick Embryo Chorioallantoic Membrane as an In Vivo Assay to Study
      Antiangiogenesis.
AB  - Antiangiogenesis, e.g., inhibition of blood vessel growth, is being investigated
      as a way to prevent the growth of tumors and other angiogenesis-dependent
      diseases. Pharmacological inhibition interferes with the angiogenic cascade or
      the immature neovasculature with synthetic or semi-synthetic substances,
      endogenous inhibitors or biological antagonists.The chick embryo chorioallantoic
      membrane (CAM) is an extraembryonic membrane, which serves as a gas exchange
      surface and its function is supported by a dense capillary network. Because its
      extensive vascularization and easy accessibility, CAM has been used to study
      morphofunctional aspects of the angiogenesis process in vivo and to study the
      efficacy and mechanism of action of pro- and anti-angiogenic molecules. The
      fields of application of CAM in the study of antiangiogenesis, including our
      personal experience, are illustrated in this review article.

PMID- 27713273
TI  - Hybridoma-Derived Idiotype Vaccine for Lymphoma: Approval Must Wait.
AB  - Hybridoma-derived idiotype vaccines have been used for the experimental treatment
      of human lymphoma over the last twenty years, providing evidence of biological
      efficacy, clinical efficacy and clinical benefit. However, the product that has
      come closer to regulatory approval is unlikely to clear that hurdle due to the
      insufficiently robust data obtained in a recently closed clinical trial. This
      review aims at discussing the reasons for hybridoma-derived idiotype vaccines,
      more difficult to produce but also more successful than recombinant idiotype
      vaccines so far, are unlikely to gain regulatory approval. In particular, it is
      necessary to examine the many peculiar features of this therapeutic approach in a
      broader context, with special attention to concepts like customized active
      immunotherapy and randomization. Most published trials based on hybridoma-derived
      idiotype vaccines are being analyzed, together with the yet non-peer reviewed
      data from the only randomized study conducted so far with this product, and with
      the main trials on recombinant idiotype vaccines for thorough comparison. All in
      all, the sole randomized trial ever conducted on hybridoma-derived idiotype
      vaccines failed to achieve its primary clinical end point because of an
      insufficient accrual and because the statistical significance achieved was not as
      stringent as required for regulatory approval.

PMID- 27713272
TI  - Dendritic Guanidines as Efficient Analogues of Cell Penetrating Peptides.
AB  - The widespread application of cell penetrating agents to clinical therapeutics
      and imaging agents relies on the ability to prepare them on a large scale and to
      readily conjugate them to their cargos. Dendritic analogues of cell penetrating
      peptides, with multiple guanidine groups on their peripheries offer advantages as
      their high symmetry allows them to be efficiently synthesized, while orthogonal
      functionalities at their focal points allow them to be conjugated to cargo using
      simple synthetic methods. Their chemical structures and properties are also
      highly tunable as their flexibility and the number of guanidine groups can be
      tuned by altering the dendritic backbone or the linkages to the guanidine groups.
      This review describes the development of cell-penetrating dendrimers based on
      several different backbones, their structure-property relationships, and
      comparisons of their efficacies with those of known cell penetrating peptides.
      The toxicities of these dendritic guanidines are also reported as well as their
      application towards the intracellular delivery of biologically significant cargos
      including proteins and nanoparticles.

PMID- 27713274
TI  - 2-Deoxystreptamine Conjugates by Truncation-Derivatization of Neomycin.
AB  - A small library of truncated neomycin-conjugates is prepared by consecutive
      removal of 2,6-diaminoglucose rings, oxidation-reductive amination of ribose,
      oxidation-conjugation of aminopyridine/aminoquinoline and finally dimerization.
      The dimeric conjugates were evaluated for antibacterial activity with a unique
      hemocyanin-based biosensor. Based on the outcome of these results, a second
      generation set of monomeric conjugates was prepared and found to display
      significant antibacterial activity, in particular with respect to kanamycin
      resistant E. coli.

PMID- 27713278
TI  - Liraglutide Therapy for Type 2 Diabetes: Overcoming Unmet Needs.
AB  - Although advances have been achieved in the management of type 2 diabetes,
      current treatment options for patients with this disease still fail to address
      disease progression, glycaemic control remains suboptimal and therapies are often
      associated with weight gain and hypoglycaemia. Thus, new antidiabetes therapies
      are being sought. Glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) are incretin hormones that have been the recent
      focus of research. The physiological action of GLP-1, in particular, has
      demonstrated its potential in addressing the therapeutic needs of patients with
      type 2 diabetes. To exploit this action, liraglutide, a human GLP-1 analogue that
      shares 97% of its amino acid sequence identity with native GLP-1, has been
      developed. In a recent phase 3 trial programme (LEAD, Liraglutide Effect and
      Action in Diabetes), treatment with liraglutide was associated with substantial
      improvements in glycaemic control and low risk of hypoglycaemia. In addition,
      reductions in weight and systolic blood pressure were reported. There is also an
      indication that liraglutide is capable of improving beta-cell function and
      increasing beta-cell mass. Thus, liraglutide may overcome the limitations with
      current therapies and help to address the unmet clinical needs of patients with
      type 2 diabetes.

PMID- 27713276
TI  - Theophylline.
AB  - Theophylline (3-methyxanthine) has been used to treat airway diseases for over 70
      years. It was originally used as a bronchodilator but the relatively high doses
      required are associated with frequent side effects, so its use declined as
      inhaled beta2-agonists became more widely used. More recently it has been shown
      to have anti-inflammatory effects in asthma and COPD at lower concentrations. The
      molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3
      and PDE4, but the anti-inflammatory effect may be due to histone deacetylase
      (HDAC) activation, resulting in switching off of activated inflammatory genes.
      Through this mechanism theophylline also reverses corticosteroid resistance and
      this may be of particular value in severe asthma and COPD where HDAC2 activity is
      markedly reduced. Theophylline is given systemically (orally as slow-release
      preparations for chronic treatment and intravenously for acute exacerbations of
      asthma) and blood concentrations are determined mainly by hepatic metabolism,
      which may be increased or decreased in several diseases and by concomitant drug
      therapy. Theophylline is now usually used as an add-on therapy in asthma patients
      not well controlled on inhaled corticosteroids and in COPD patients with severe
      disease not controlled by bronchodilator therapy. Side effects are related to
      plasma concentrations and include nausea, vomiting and headaches due to PDE
      inhibition and at higher concentrations to cardiac arrhythmias and seizures due
      to adenosine A1-receptor antagonism.

PMID- 27713279
TI  - Implications of Inter-Individual Differences in Clopidogrel Metabolism, with
      Focus on Pharmacogenetics.
AB  - Increasing evidence for the role of pharmacogenetics in treatment resistance to
      the antiplatelet agent clopidogrel has been gained during the last years. Apart
      from CYP2C19 genetic polymorphisms, nongenetic factors, particularly drug-drug
      interactions, age and other clinical characteristics influence the
      interindividual variability in clopidogrel response to varying degrees. The
      present article reviews the so far accumulated evidence on the role of
      pharmacogenetic traits influencing CYP-activity as determinants of the
      antiplatelet response to clopidogrel, and its clinical implications. The genetic
      variation in CYP2C19 activity seems to influence short- and long-term
      antithrombotic effects of clopidogrel to a substantial extent. Prediction models
      for clopidogrel non-responsiveness that include CYP2C19 genotyping together with
      relevant non-genetic risk factors are needed to be verified for their potential
      benefit in individualization of antithrombotic therapy.

PMID- 27713275
TI  - Oxytocin and Major Depressive Disorder: Experimental and Clinical Evidence for
      Links to Aetiology and Possible Treatment.
AB  - Affective disorders represent the most common psychiatric diseases, with
      substantial co-morbidity existing between major depressive disorders (MDD) and
      anxiety disorders. The lack of truly novel acting compounds has led to non
      monoaminergic based research and hypotheses in recent years. The large number of
      brain neuropeptides, characterized by discrete synthesis sites and multiple
      receptors, represent likely research candidates for novel therapeutic targets.
      The present review summarises the available preclinical and human evidence
      regarding the neuropeptide, oxytocin, and its implications in the aetiology and
      treatment of MDD. While the evidence is not conclusive at present additional
      studies are warranted to determine whether OXT may be of therapeutic benefit in
      subsets of MDD patients such as those with comorbid anxiety symptoms and low
      levels of social attachment.

PMID- 27713277
TI  - Phytochemicals in the Control of Human Appetite and Body Weight.
AB  - Since obesity has grown to epidemic proportions, its effective management is a
      very important clinical issue. Despite the great amount of scientific effort that
      has been put into understanding the mechanisms that lead to overconsumption and
      overweight, at the moment very few approaches to weight management are effective
      in the long term. On the other hand, modern society is also affected by the
      growing incidence of eating disorders on the other side of the spectrum such as
      anorexia and bulimia nervosa which are equally difficult to treat. This review
      will try to summarise the main findings available in the literature regarding the
      effect of plants or plant extracts (phytochemicals) on human appetite and body
      weight. The majority of plant extracts are not single compounds but rather a
      mixture of different molecules, therefore their mechanism of action usually
      targets several systems. In addition, since some cellular receptors tend to be
      widely distributed, sometimes a single molecule can have a widespread effect.
      This review will attempt to describe the main phytochemicals that have been
      suggested to affect the homeostatic mechanisms that influence intake and body
      weight. Clinical data will be summarised and scientific evidence will be
      reviewed.

PMID- 27713280
TI  - Lambda Interferons: New Cytokines with Old Functions.
AB  - Interferon lambda (IFN-lambda) is a member of the class II cytokine family, and
      like the other members of this family, they are small helical proteins. Since
      their discovery significant efforts have been made to determine their role in
      innate and adaptive immunity. Their strong antiviral activity, both in vitro and
      in vivo, has firmly established their interferon status. However, in contrast to
      type I interferon, only a very limited subset of cells/tissues responds to
      interferon lambda. In addition to inducing an antiviral state in responsive
      cells, recent data suggest that IFN-l plays a role in shaping the adaptive immune
      response. However, the data is not in complete agreement regarding the effect of
      IFN-lambda on the adaptive immune system. Recently IFN-l has entered clinical
      trials against hepatitis C Virus and IFN-l is a promising future therapeutic,
      against different viruses replicating in responsive tissues, like that of the
      airway epithelia. In this review we describe the knowledge acquired during the
      past six years about the structure and function of interferon lambda.

PMID- 27713281
TI  - Synthetic Medicinal Chemistry in Chagas' Disease: Compounds at The Final Stage of
      "Hit-To-Lead" Phase.
AB  - Chagas' disease, or American trypanosomosiasis, has been the most relevant
      illness produced by protozoa in Latin America. Synthetic medicinal chemistry
      efforts have provided an extensive number of chemodiverse hits at the "active-to
      hit" stage. However, only a more limited number of these have been studied in
      vivo in models of Chagas' disease. Herein, we survey some of the cantidates able
      to surpass the "hit-to-lead" stage discussing their limitations or merit to enter
      in clinical trials in the short term.

PMID- 27713282
TI  - Combating Combination of Hypertension and Diabetes in Different Rat Models.
AB  - Rat experimental models are used extensively for studying physiological
      mechanisms and treatments of hypertension and diabetes co-existence. Each one of
      these conditions is a major risk factor for cardiovascular disease (CVD), and the
      combination of the two conditions is a potent enhancer of CVD. Five major animal
      models that advanced our understanding of the mechanisms and therapeutic
      approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB,
      SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH) rats. The use of
      various drugs, such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs),
      various angiotensin receptor blockers (ARBs), and calcium channel blockers
      (CCBs), to combat the effects of concomitant pathologies on the combination of
      diabetes and hypertension, as well as the non-pharmacological approach are
      reviewed in detail for each rat model. Results from experiments on these models
      indicate that classical factors contributing to the pathology of hypertension and
      diabetes combination-Including hypertension, hyperglycemia, hyperinsulinemia and
      hyperlipidemia-can now be treated, although these treatments do not completely
      prevent renal complications. Animal studies have focused on several mechanisms
      involved in hypertension/diabetes that remain to be translated into clinical
      medicine, including hypoxia, oxidative stress, and advanced glycation. Several
      target molecules have been identified that need to be incorporated into a
      treatment modality. The challenge continues to be the identification and
      interpretation of the clinical evidence from the animal models and their
      application to human treatment.

PMID- 27713283
TI  - The Renin-Angiotensin System in the Development of Salt-Sensitive Hypertension in
      Animal Models and Humans.
AB  - Hypertension is still one of the major causes of death from cardiovascular
      failure. Increased salt intake may aggravate the rise in blood pressure and the
      development of consequential damage of the heart, the vessels and other organs.
      The general necessity of restricted salt intake regardless of blood pressure or
      salt sensitivity has been a matter of debate over the past decades. This review
      summarizes the main pathogenic mechanisms of hypertension and salt sensitivity in
      rat models, particularly in the spontaneously hypertensive rat (SHR), and in
      patients with essential hypertension (EH). Although SHRs are commonly considered
      to be salt-resistant, there is much evidence that salt loading may deteriorate
      blood pressure and cardiovascular function even in these animals. Similarly, EH
      is not a homogenous disorder - some patients, but not all, exhibit pronounced
      salt sensitivity. The renin-angiotensin system (RAS) plays a key role in the
      regulation of blood pressure and salt and fluid homeostasis and thus is one of
      the main targets of antihypertensive therapy. This review focuses on the
      contribution of the RAS to the pathogenesis of salt-sensitive hypertension in
      SHRs and patients with EH.

PMID- 27713286
TI  - Cell-Penetrating Peptides: A Comparative Study on Lipid Affinity and Cargo
      Delivery Properties.
AB  - A growing number of natural and/or synthetic peptides with cell membrane
      penetrating capability have been identified and described in the past years.
      These molecules have been considered promising tools for delivering bioactive
      compounds into various cell types. Although the mechanism of uptake is still
      unclear, it is reasonable to assume that the relative contribute of each proposed
      mechanism could differ for the same peptide, depending on experimental protocol
      and cargo molecule composition. In this work we try to connect the capability to
      interact with model lipid membrane and structural and chemical characteristics of
      CPPs in order to obtain a biophysical classification that predicts the behavior
      of CPP-cargo molecules in cell systems. Indeed, the binding with cell membrane is
      one of the primary step in the interaction of CPPs with cells, and consequently
      the studies on model membrane could become important for understanding peptide
      membrane interaction on a molecular level, explaining how CPPs may translocate a
      membrane without destroying it and how this interactions come into play in
      shuttling CPPs via different routes with different efficiency. We analyzed by CD
      and fluorescence spectroscopies the binding properties of six different CPPs
      (kFGF, Nle54-Antp and Tat derived peptides, and oligoarginine peptides containing
      6, 8 or 10 residues) in absence or presence of the same cargo peptide (the 392
      401pTyr396 fragment of HS1 protein). The phospholipid binding properties were
      correlated to the conformational and chemical characteristics of peptides, as
      well as to the cell penetrating properties of the CPP-cargo conjugates. Results
      show that even if certain physico-chemical properties (conformation, positive
      charge) govern CPP capability to interact with the model membrane, these cannot
      fully explain cell-permeability properties.

PMID- 27713287
TI  - Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its
      Analogs.
AB  - We developed an efficient, stereoselective synthetic method for the
      diketopiperazine moiety of neoechinulin A and its derivatives. The intramolecular
      cyclization at 80 oC proceeded with minimal racemization of the stereogenic
      center at C-12 on neoechinulin A, even though the cyclization at 110 oC caused
      partial racemization. In contrast with these results, the cyclization on
      diketopiperazine of 8,9-dihydroneoechinulin A derivatives did not cause
      epimerization of the stereogenic centers, even at 110  degrees C. We examined the
      structure-activity relationships for the cytoprotective activity against
      cytotoxicity induced by 3-morpholinosydnonimine (SIN-1) in nerve growth factor
      (NGF)-differentiated PC12 cells. The C-8/C-9 double bond, but not the stereogenic
      center derived from alanine, was found to play a key role in the cytoprotective
      activity.

PMID- 27713288
TI  - Lessons Learned from Surveillance of Antimicrobial Susceptibilities of
      Pseudomonas aeruginosa at a Large Academic Medical Center.
AB  - This research report assessed the differences in resistance rates and
      antimicrobial usage-versus-susceptibility relationships of Pseudomonas aeruginosa
      found in various hospital patient care areas. A simplified case control study was
      also performed to identify patient-specific risk factors associated with cefepime
      resistant P. aeruginosa isolates. Last, we determined the consequence of
      combining mucoid and non-mucoid derived antimicrobial susceptibilities of
      P.aeruginosa into hospital antibiograms. Overall, susceptibility rates remained
      lower in the intensive care units (ICUs) compared to the non-ICU patient care
      areas, except for cefepime over the last time period. Cefepime utilization and
      antimicrobial-resistance rates among P. aeruginosa isolates had a significant
      relationship. Decreased meropenem exposure was associated with lower resistance
      rates relative to cefepime. Risk factors independently associated with cefepime
      resistant P. aeruginosa were structural lung disease, ICU admission, recent third
      generation cephalosporin use, frequent hospital admission and non-urine isolates.
      Large and statistically significant differences were observed between non-mucoid
      and combined percent susceptibility data for aminoglycosides. To control
      antimicrobial resistance and optimize initial empiric antimicrobial therapy,
      antimicrobial susceptibility and utilization patterns in specific patient care
      areas should be monitored and risk factors for antimicrobial resistance should be
      assessed. Mucoid strains of P. aeruginosa should not be included into
      antimicrobial susceptibility data as this may underestimate activity of most
      antipseudomonal agents.

PMID- 27713290
TI  - Imperatoxin A, a Cell-Penetrating Peptide from Scorpion Venom, as a Probe of Ca2+
      Release Channels/Ryanodine Receptors.
AB  - Scorpion venoms are rich in ion channel-modifying peptides, which have proven to
      be invaluable probes of ion channel structure-function relationship. We
      previously isolated imperatoxin A (IpTxa), a 3.7 kDa peptide activator of Ca2+
      release channels/ryanodine receptors (RyRs) [1,2,3] and founding member of the
      calcin family of scorpion peptides. IpTxa folds into a compact, mostly
      hydrophobic molecule with a cluster of positively-charged, basic residues
      polarized on one side of the molecule that possibly interacts with the
      phospholipids of cell membranes. To investigate whether IpTxa permeates external
      cellular membranes and targets RyRs in vivo, we perfused IpTxa on intact
      cardiomyocytes while recording field-stimulated intracellular Ca2+ transients. To
      further investigate the cell-penetrating capabilities of the toxin, we prepared
      thiolated, fluorescent derivatives of IpTxa. Biological activity and
      spectroscopic properties indicate that these derivatives retain high affinity for
      RyRs and are only 5- to 10-fold less active than native IpTxa. Our results
      demonstrate that IpTxa is capable of crossing cell membranes to alter the release
      of Ca2+in vivo, and has the capacity to carry a large, membrane-impermeable cargo
      across the plasma membrane, a finding with exciting implications for novel drug
      delivery.

PMID- 27713285
TI  - Beta-Adrenergic Agonists.
AB  - Inhaled beta2-adrenoceptor (beta2-AR) agonists are considered essential
      bronchodilator drugs in the treatment of bronchial asthma, both as symptoms
      relievers and, in combination with inhaled corticosteroids, as disease
      controllers. In this article, we first review the basic mechanisms by which the
      beta2-adrenergic system contributes to the control of airway smooth muscle tone.
      Then, we go on describing the structural characteristics of beta2-AR and the
      molecular basis of G-protein-coupled receptor signaling and mechanisms of its
      desensitization/ dysfunction. In particular, phosphorylation mediated by protein
      kinase A and beta-adrenergic receptor kinase are examined in detail. Finally, we
      discuss the pivotal role of inhaled beta2-AR agonists in the treatment of asthma
      and the concerns about their safety that have been recently raised.

PMID- 27713284
TI  - Cell-Penetrating Peptides-Mechanisms of Cellular Uptake and Generation of
      Delivery Systems.
AB  - The successful clinical application of nucleic acid-based therapeutic strategies
      has been limited by the poor delivery efficiency achieved by existing vectors.
      The development of alternative delivery systems for improved biological activity
      is, therefore, mandatory. Since the seminal observations two decades ago that the
      Tat protein, and derived peptides, can translocate across biological membranes,
      cell-penetrating peptides (CPPs) have been considered one of the most promising
      tools to improve non-invasive cellular delivery of therapeutic molecules. Despite
      extensive research on the use of CPPs for this purpose, the exact mechanisms
      underlying their cellular uptake and that of peptide conjugates remain
      controversial. Over the last years, our research group has been focused on the
      S413-PV cell-penetrating peptide, a prototype of this class of peptides that
      results from the combination of 13-amino-acid cell penetrating sequence derived
      from the Dermaseptin S4 peptide with the SV40 large T antigen nuclear
      localization signal. By performing an extensive biophysical and biochemical
      characterization of this peptide and its analogs, we have gained important
      insights into the mechanisms governing the interaction of CPPs with cells and
      their translocation across biological membranes. More recently, we have started
      to explore this peptide for the intracellular delivery of nucleic acids (plasmid
      DNA, siRNA and oligonucleotides). In this review we discuss the current knowledge
      of the mechanisms responsible for the cellular uptake of cell-penetrating
      peptides, including the S413-PV peptide, and the potential of peptide-based
      formulations to mediate nucleic acid delivery.

PMID- 27713289
TI  - Non Steroidal Anti-Inflammatory Drugs and Inflammatory Bowel Disease.
AB  - Inflammatory Bowel Diseases (IBD) are an immune mediated chronic or relapsing
      disorders of the gastrointestinal (GI) tract. IBD is characterized by a chronic
      intestinal inflammatory process with various components contributing to the
      pathogenesis of the disease including environmental factors such as smoking or
      use of Non Steroidal Anti-Inflammatory Drugs (NSAIDS). NSAIDS are among the most
      commonly used medications for the treatment of various inflammatory conditions.
      The main factor limiting NSAIDS use is the concern for the development of
      gastrointestinal toxicity including mucosal injury. A possible association
      between the use of NSAIDS and the onset or relapse of IBD has been repeatedly
      suggested. This article will review the current concepts and evidence of the
      relationship between IBD and NSAIDS.

PMID- 27713291
TI  - Ingested Type I Interferon-State of the Art as Treatment for Autoimmunity Part 2.
AB  - We have proposed a unifying hypothesis of the etiopathogenesis of autoimmunity
      that defines autoimmunity as a type I interferon (IFN) immunodeficiency syndrome.
      We have examined toxicity and potential efficacy in two phase I (type 1 diabetes
      [T1D], multiple sclerosis [MS]) and phase II clinical trials in T1D and MS. In a
      phase I open label trial in T1D, ingested IFN-alpha preserved residual beta-cell
      function in recent onset patients. In a second phase I trial in MS, there was a
      significant decrease in peripheral blood mononuclear cell IL-2 and IFN-gamma
      production after ingesting IFN-alpha. In a phase II randomized, placebo
      controlled, double-blind trial in MS, 10,000 IU ingested IFN-alpha significantly
      decreased gadolinium enhancements compared to the placebo group at month 5. TNF
      alpha and IFN-gamma cytokine secretion in the 10,000 IU group at month 5 showed a
      significant decrease that corresponded with the effect of ingested IFN-alpha on
      decreasing gadolinium enhancements. In a phase II randomized, placebo-controlled,
      double-blind trial in T1D, patients in the 5,000 unit hrIFN-alpha treatment group
      maintained more beta-cell function one year after study enrollment compared to
      individuals in the placebo group. Ingested IFN-alpha was not toxic in these
      clinical trials. These studies suggest that ingested IFN-alpha may have a
      potential role in the treatment of autoimmunity.

PMID- 27713292
TI  - The Impact of CYP2D6 Genotyping on Tamoxifen Treatment.
AB  - Tamoxifen remains a cornerstone of treatment for patients with oestrogen-receptor
      positive breast cancer. Tamoxifen efficacy depends on the biotransformation,
      predominantly via the cytochrome P450 2D6 (CYP2D6) isoform, to the active
      metabolite endoxifen. Both genetic and environmental (drug-induced) factors may
      alter CYP2D6 enzyme activity directly affecting the concentrations of active
      tamoxifen metabolites. Several studies suggest that germline genetic variants in
      CYP2D6 influence the clinical outcomes of patients treated with adjuvant
      tamoxifen. Here, we review the existing data relating CYP2D6 genotypes to
      tamoxifen efficacy.

PMID- 27713293
TI  - Lysostaphin: A Staphylococcal Bacteriolysin with Potential Clinical Applications.
AB  - Lysostaphin is an antimicrobial agent belonging to a major class of antimicrobial
      peptides and proteins known as the bacteriocins. Bacteriocins are bacterial
      antimicrobial peptides which generally exhibit bactericidal activity against
      other bacteria. Bacteriocin production is a self-protection mechanism that helps
      the microorganisms to survive in their natural habitats. Bacteriocins are
      currently distributed into three main classes. Staphylococcins are bacteriocins
      produced by staphylococci, which are Gram-positive bacteria of medical and
      veterinary importance. Lysostaphin is the only class III staphylococcin described
      so far. It exhibits a high degree of antistaphylococcal bacteriolytic activity,
      being inactive against bacteria of all other genera. Infections caused by
      staphylococci continue to be a problem worldwide not only in healthcare
      environments but also in the community, requiring effective measures for
      controlling their spread. Since lysostaphin kills human and animal staphylococcal
      pathogens, it has potential biotechnological applications in the treatment of
      staphylococcal infections. In vitro and in vivo studies performed with
      lysostaphin have shown that this staphylococcin has potential to be used, solely
      or in combination with other antibacterial agents, to prevent or treat bacterial
      staphylococcal infectious diseases.

PMID- 27713295
TI  - A Review of Anti-Inflammatory Drug-Induced Gastrointestinal Injury: Focus on
      Prevention of Small Intestinal Injury.
AB  - Capsule endoscopy and balloon endoscopy, advanced modalities that allow full
      investigation of the entire small intestine, have revealed that nonsteroidal anti
      inflammatory drugs (NSAIDs) can cause a variety of abnormalities in the small
      intestine. Recently, several reports show that traditional NSAIDs (tNSAIDs) and
      acetylsalicylic acid (ASA) can induce small intestinal injuries. These reports
      have shown that the preventive effect of proton pump inhibitors (PPIs) does not
      extend to the small intestine, suggesting that concomitant therapy may be
      required to prevent small intestinal side effects associated with tNSAID/ASA use.
      Recently, several randomized controlled trials used capsule endoscopy to evaluate
      the preventive effect of mucoprotective drugs against tNSAID/ASA-induced small
      intestinal injury. These studies show that misoprostol and rebamipide reduce the
      number and types of tNSAID-induced small intestinal mucosal injuries. However,
      those studies were limited to a small number of subjects and tested short-term
      tNSAID/ ASA treatment. Therefore, further extensive studies are clearly required
      to ascertain the beneficial effect of these drugs.

PMID- 27713294
TI  - Safety, Tolerability, and Immunogenicity of Interferons.
AB  - Interferons (IFNs) are class II cytokines that are key components of the innate
      immune response to virus infection. Three IFN sub-families, type I, II, and III
      IFNs have been identified in man, Recombinant analogues of type I IFNs, in
      particular IFNalpha2 and IFNbeta1, have found wide application for the treatment
      of chronic viral hepatitis and remitting relapsing multiple sclerosis
      respectively. Type II IFN, or IFN gamma, is used principally for the treatment of
      chronic granulomatous disease, while the recently discovered type III IFNs, also
      known as IFN lambda or IL-28/29, are currently being evaluated for the treatment
      of chronic viral hepatitis. IFNs are in general well tolerated and the most
      common adverse events observed with IFNalpha or IFNbeta therapy are "flu-like"
      symptoms such as fever, headache, chills, and myalgia. Prolonged treatment is
      associated with more serious adverse events including leucopenia,
      thrombocytopenia, increased hepatic transaminases, and neuropsychiatric effects.
      Type I IFNs bind to high-affinity cell surface receptors, composed of two
      transmembrane polypeptides IFNAR1 and IFNAR2, resulting in activation of the
      Janus kinases Jak1 and Tyk2, phosphorylation and activation of the latent
      cytoplasmic signal transducers and activators of transcription (STAT1) and STAT2,
      formation of a transcription complex together with IRF9, and activation of a
      specific set of genes that encode the effector molecules responsible for
      mediating the biological activities of type I IFNs. Systemic administration of
      type I IFN results in activation of IFN receptors present on essentially all
      types of nucleated cells, including neurons and hematopoietic stem cells, in
      addition to target cells. This may well explain the wide spectrum of IFN
      associated toxicities. Recent reports suggest that certain polymorphisms in type
      I IFN signaling molecules are associated with IFN-induced neutropenia and
      thrombocytopenia in patients with chronic hepatitis C. IFNgamma binds to a cell
      surface receptor composed of two transmembrane polypeptides IFGR1 and IFGR2
      resulting in activation of the Janus kinases Jak1 and Jak2, phosphorylation of
      STAT1, formation of STAT1 homodimers, and activation of a specific set of genes
      that encode the effector molecules responsible for mediating its biological
      activity. In common with type I IFNs, IFNgamma receptors are ubiquitous and a
      number of the genes activated by IFNgamma are also activated by type I IFNs that
      may well account for a spectrum of toxicities similar to that associated with
      type I IFNs including "flu-like" symptoms, neutropenia, thrombocytopenia, and
      increased hepatic transaminases. Although type III IFNs share the major
      components of the signal transduction pathway and activate a similar set of IFN
      stimulated genes (ISGs) as type I IFNs, distribution of the IFNlambda receptor is
      restricted to certain cell types suggesting that IFNlambda therapy may be
      associated with a reduced spectrum of toxicities relative to type I or type II
      IFNs. Repeated administration of recombinant IFNs can cause in a break in immune
      tolerance to self-antigens in some patients resulting in the production of
      neutralizing antibodies (NABs) to the recombinant protein homologue. Appearance
      of NABs is associated with reduced pharmacokinetics, pharmacodynamics, and a
      reduced clinical response. The lack of cross-neutralization of IFNbeta by anti
      IFNalpha NABs and vice versa, undoubtedly accounts for the apparent lack of
      toxicity associated with the presence of anti-IFN NABs with the exception of
      relatively mild infusion/injection reactions.

PMID- 27713297
TI  - Tyrosine Kinase Inhibitors as Antiangiogenic Drugs in Multiple Myeloma.
AB  - Tyrosine kinase inhibitors are a new class of anticancer drugs, that are capable
      of directly interacting with the catalytic site of the target enzyme and thereby
      inhibiting catalysis. Therapeutically useful tyrosine kinase inhibitors are not
      specific for a single tyrosine kinase, but rather they are selective against a
      limited number of tyrosine kinases. The success of imatinib-mesylate (Gleevec(r))
      for the treatment of patients with chronic myeloid leukemia has opened a
      intensive search for new small molecular compounds able to target other protein
      tyrosine kinases involved in the malignant transformation. This review article is
      focused on the use of tyrosine kinase inhibitors as antiangiogenic molecules in
      the treatment of multiple myeloma.

PMID- 27713296
TI  - New Trends in Cancer Therapy: Targeting Ion Channels and Transporters.
AB  - The expression and activity of different channel types mark and regulate specific
      stages of cancer establishment and progression. Blocking channel activity impairs
      the growth of some tumors, both in vitro and in vivo, which opens a new field for
      pharmaceutical research. However, ion channel blockers may produce serious side
      effects, such as cardiac arrhythmias. For instance, Kv11.1 (hERG1) channels are
      aberrantly expressed in several human cancers, in which they control different
      aspects of the neoplastic cell behaviour. hERG1 blockers tend to inhibit cancer
      growth. However they also retard the cardiac repolarization, thus lengthening the
      electrocardiographic QT interval, which can lead to life-threatening ventricular
      arrhythmias. Several possibilities exist to produce less harmful compounds, such
      as developing specific drugs that bind hERG1 channels in the open state or
      disassemble the ion channel/integrin complex which appears to be crucial in
      certain stages of neoplastic progression. The potential approaches to improve the
      efficacy and safety of ion channel targeting in oncology include: (1) targeting
      specific conformational channel states; (2) finding ever more specific
      inhibitors, including peptide toxins, for channel subtypes mainly expressed in
      well-identified tumors; (3) using specific ligands to convey traceable or
      cytotoxic compounds; (4) developing channel blocking antibodies; (5) designing
      new molecular tools to decrease channel expression in selected cancer types.
      Similar concepts apply to ion transporters such as the Na+/K+ pump and the Na+/H+
      exchanger. Pharmacological targeting of these transporters is also currently
      being considered in anti-neoplastic therapy.

PMID- 27713298
TI  - Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in
      Models of Neurodegeneration.
AB  - Cdk5 is essential for neuronal differentiation processes in the brain. Activation
      of Cdk5 requires the association with the mostly neuron-specific p35 or p39.
      Overactivation of CDK5 by cleavage of p35 into p25 is thought to be involved in
      neurodegenerative processes. Here, we have tested an approach to inhibit
      pathological Cdk5 activation with a Tat-linked dominant-negative fragment of p25.
      It reduced cell death induced by staurosporine and showed a tendency to alleviate
      manganese-induced cell death, while it did not protect against 6-OHDA toxicity.
      Our results suggest that the Tat technique is a suitable tool to inhibit
      dysregulated CDK5.

PMID- 27713300
TI  - Significant Acute Kidney Injury Due to Non-steroidal Anti-inflammatory Drugs:
      Inpatient Setting.
AB  - In the United States non-steroidal anti-inflammatory drugs (NSAID) are freely
      available over-the-counter. Because of the adverse effects on the kidneys and the
      popularity of these drugs, unregulated use of NSAIDs is an under recognized and
      potentially dangerous problem. Fifteen inpatients, mean age of 15.2 +/- 2.3 years
      (five males, 10 females), were referred to nephrology for acute kidney injury.
      All patients admitted to taking ibuprofen and six also consumed naproxen. None of
      the patients had underlying renal diseases at the time of admission. Nine
      patients had proteinuria and 12 had hematuria (including one with gross
      hematuria). One patient had nephrotic syndrome but the condition resolved
      spontaneously without steroids and has remained in remission for four years. Two
      patients required dialysis. Only one of the dialyzed patients required steroid
      therapy for recovery of renal function. The mean duration of hospitalization was
      7.4 +/- 5.5 days. The serum creatinine peaked at 4.09 +/- 4.24 (range 1.2-15.3)
      mg/dL. All patients recovered renal function with normalization of serum
      creatinine to 0.71 +/- 0.15 mg/dL. The estimated GFR (glomerular filtration rate)
      at peak of renal failure was 38.2 +/- 20.5 mL/min but did improve to a baseline
      of 134 +/- 26.2 mL/min (range 89-177, p < 0.01). However, the duration from onset
      to normalization of serum creatinine was 37 +/- 42 days indicating that majority
      of patients had abnormal renal function for a prolonged period. In conclusion,
      NSAIDs pose a significant risk of renal failure for significant duration and as
      an entity may be under recognized.

PMID- 27713302
TI  - The Treatment of Melioidosis.
AB  - Melioidosis is a complex bacterial infection, treatment of which combines the
      urgency of treating rapidly fatal Gram negative septicaemia with the need for
      eradication of long-term persistent disease in pulmonary, soft tissue, skeletal
      and other organ systems. Incremental improvements in treatment have been made as
      a result of multicentre collaboration across the main endemic region of Southeast
      Asia and northern Australia. There is an emerging consensus on the three main
      patterns of antimicrobial chemotherapy; initial (Phase 1) treatment, subsequent
      eradication (Phase 2) therapy and most recently post-exposure (Phase 0)
      prophylaxis. The combination of agents used, duration of therapy and need for
      adjunct modalities depends on the type, severity and antimicrobial susceptibility
      of infection. New antibiotic and adjunct therapies are at an investigational
      stage but on currently available data are unlikely to make a significant impact
      on this potentially fatal infection.

PMID- 27713301
TI  - Effects of NSAIDs on the Inner Ear: Possible Involvement in Cochlear Protection.
AB  - Cyclooxygenase and lipoxygenase, two important enzymes involved in arachidonic
      acid metabolism, are major targets of non-steroidal anti-inflammatory drugs
      (NSAIDs). Recent investigations suggest that arachidonic cascades and their
      metabolites may be involved in maintaining inner ear functions. The excessive use
      of aspirin may cause tinnitus in humans and impairment of the outer hair cell
      functions in experimental animals. On the other hand, NSAIDs reportedly exhibit
      protective effects against various kinds of inner ear disorder. The present
      review summarizes the effects of NSAIDs on cochlear pathophysiology. NSAIDs are a
      useful ameliorative adjunct in the management of inner ear disorders.

PMID- 27713303
TI  - The Role of Non-Steroidal Anti-Inflammatory Drugs in Renal Colic.
AB  - NSAIDs provide optimal analgesia in renal colic due to the reduction in
      glomerular filtration and renal pelvic pressure, ureteric peristalsis and
      ureteric oedema. Prevention of glomerular afferent arteriolar vasodilatation
      renders these patients at risk of renal impairment. NSAIDs have the additional
      benefit of reducing the number of new colic episodes and preventing subsequent
      readmission to hospital. Despite recent work promoting the use of pharmacological
      agents to improve stone passage rates, NSAIDs do not appear to reduce the time to
      stone passage or increase the likelihood of stone passage in renal colic.

PMID- 27713299
TI  - Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents
      Endowed with Multiple Mechanisms of Action.
AB  - Uncontrolled neovascularization occurs in several angiogenesis-dependent
      diseases, including cancer. Neovascularization is tightly controlled by the
      balance between angiogenic growth factors and antiangiogenic agents. The various
      natural angiogenesis inhibitors identified so far affect neovascularization by
      different mechanisms of action. Thrombospondin-1 (TSP-1) is a matricellular
      modular glycoprotein that acts as a powerful endogenous inhibitor of
      angiogenesis. It acts both indirectly, by sequestering angiogenic growth factors
      and effectors in the extracellular environment, and directly, by inducing an
      antiangiogenic program in endothelial cells following engagement of specific
      receptors including CD36, CD47, integrins and proteoglycans (all involved in
      angiogenesis ). In view of its central, multifaceted role in angiogenesis, TSP-1
      has served as a source of antiangiogenic tools, including TSP-1 fragments,
      synthetic peptides and peptidomimetics, gene therapy strategies, and agents that
      up-regulate TSP-1 expression. This review discusses TSP-1-based inhibitors of
      angiogenesis, their mechanisms of action and therapeutic potential, drawing our
      experience with angiogenic growth factor-interacting TSP-1 peptides, and the
      possibility of exploiting them to design novel antiangiogenic agents.

PMID- 27713304
TI  - Prospects for the Use of ATR Inhibitors to Treat Cancer.
AB  - ATR is an apical kinase in one of the DNA-damage induced checkpoint pathways.
      Despite the development of inhibitors of kinases structurally related to ATR, as
      well as inhibitors of the ATR substrate Chk1, no ATR inhibitors have yet been
      developed. Here we review the effects of ATR downregulation in cancer cells and
      discuss the potential for development of ATR inhibitors for clinical use.

PMID- 27713306
TI  - Health Economics of Antibiotics.
AB  - Antibiotics have made a significant contribution to improving patient health, but
      policy makers and health care payers are concerned about the costs of antibiotics
      in addition to their effectiveness. This paper aims to assess the value of
      antibiotics by examining incremental cost-utility ratios of antibiotics. Evidence
      was derived from cost-utility analyses of antibiotics included in the Tufts-New
      England Center Cost-Effectiveness Analysis Registry through September 2009. The
      analysis included 85 incremental cost-utility ratios from 23 cost-utility
      analyses. The findings showed that 38.8% of incremental cost-utility ratios
      related to dominant antibiotics (i.e., more effective and less costly than the
      comparator); 45.9% referred to antibiotics that improved effectiveness, but also
      increased costs; and 15.3% related to dominated antibiotics (i.e., less effective
      and more costly than the comparator). The median ratio was 748 ? per quality
      adjusted life year. Using threshold values of 20,000 ? per quality-adjusted life
      year and 50,000 ? per quality-adjusted life year, the probability that an
      antibiotic provides value for money was 64% and 67%, respectively. The current
      evidence base suggests that the majority of antibiotics provide value for money
      and that antibiotics can aid decision makers to attain further population health
      improvements, whilst containing pharmaceutical expenditures.

PMID- 27713305
TI  - NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous
      System.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) act upon peripheral tissues and
      upon the central nervous system to produce analgesia. A major central target of
      NSAIDs is the descending pain control system. The rostral structures of the
      descending pain control system send impulses towards the spinal cord and regulate
      the transmission of pain messages. Key structures of the descending pain control
      system are the periaqueductal gray matter (PAG) and the rostral ventromedial
      region of the medulla (RVM), both of which are critical targets for endogenous
      opioids and opiate pharmaceuticals. NSAIDs also act upon PAG and RVM to produce
      analgesia and, if repeatedly administered, induce tolerance to themselves and
      cross-tolerance to opioids. Experimental evidence shows that this is due to an
      interaction of NSAIDs with endogenous opioids along the descending pain control
      system. Analgesia by NSAIDs along the descending pain control system also
      requires an activation of the CB1 endocannabinoid receptor. Several experimental
      approaches suggest that opioids, NSAIDs and cannabinoids in PAG and RVM cooperate
      to decrease GABAergic inhibition and thus enhance the descending flow of impulses
      that inhibit pain.

PMID- 27713307
TI  - Lp-PLA2 Inhibition-The Atherosclerosis Panacea?
AB  - Based on the complex pathophysiology of atherosclerosis, a large number of
      biomarkers that relate to lipids, inflammation, immunity, thrombosis and
      hemostasis, have been investigated experimentally, in epidemiologic studies and
      in clinical trials. Interest focuses on their potential role to aid in risk
      stratification, as possible surrogate markers of atherosclerosis, and potential
      targets for therapy. More recently, one lipid associated biomarker, lipoprotein
      associated phospholipase A2 (Lp-PLA2), has gained considerable interest. In
      addition to a plausible pathophysiological role by generating pro-inflammatory
      and pro-atherogenic compounds from oxidized LDL in the vessel wall, there is a
      large, fairly consistent epidemiological database indicating that increased
      levels of Lp-PLA2 mass or activity are associated with increased risk for
      cardiovascular outcomes; such data further suggest that it might improve risk
      stratification. In addition, clinical studies indicate that increased Lp-PLA2
      levels are associated with endothelial dysfunction. Moreover, it may also serve
      as an interesting therapeutic target, since a specific inhibitor of the enzyme is
      available with promising animal data and initial positive data in humans. Recent
      experimental data from a hyperlipidemic diabetic pig model strongly suggest that
      increased Lp-PLA2 in the vessel wall is associated with a more vulnerable plaque
      phenotype which can be modulated by inhibiting Lp-PLA2 activity. A biomarker
      study in more than 1,000 patients with CHD over three months has demonstrated a
      positive effect on various inflammatory molecules. In addition, an imaging study
      using IVUS based modalities (greyscale, virtual histology, and palpography)
      together with a panel of biomarkers (IBIS-2) has been done in more than 300
      patients with CHD treated over 12 months and results indicate that the
      progression of the necrotic core of the plaque can be retarded. Inhibition of the
      pro-atherogenic and pro-inflammatory effects of Lp-PLA2 may therefore contribute
      to decrease the residual risk in high risk patients already on
      polypharmacotherapy. This hypothesis is now being tested in two large phase 3
      clinical trials. Thus, Lp-PLA2 indeed may represent a biomarker and a promising
      target for intervention.

PMID- 27713308
TI  - Combining Biofilm-Controlling Compounds and Antibiotics as a Promising New Way to
      Control Biofilm Infections.
AB  - Many bacteria grow on surfaces forming biofilms. In this structure, they are well
      protected and often high dosages of antibiotics cannot clear infectious biofilms.
      The formation and stabilization of biofilms are mediated by diffusible
      autoinducers (e.g. N-acyl homoserine lactones, small peptides, furanosyl borate
      diester). Metabolites interfering with this process have been identified in
      plants, animals and microbes, and synthetic analogues are known. Additionally,
      this seems to be not the only way to control biofilms. Enzymes capable of
      cleaving essential components of the biofilm matrix, e.g. polysaccharides or
      extracellular DNA, and thus weakening the biofilm architecture have been
      identified. Bacteria also have mechanisms to dissolve their biofilms and return
      to planktonic lifestyle. Only a few compounds responsible for the signalling of
      these processes are known, but they may open a completely novel line of biofilm
      control. All these approaches lead to the destruction of the biofilm but not the
      killing of the pathogens. Therefore, a combination of biofilm-destroying
      compounds and antibiotics to handle biofilm infections is proposed. In this
      article, different approaches to combine biofilm-controlling compounds and
      antibiotics to fight biofilm infections are discussed, as well as the balance
      between biofilm formation and virulence.

PMID- 27713309
TI  - Effects of NSAIDs on Differentiation and Function of Human and Murine Osteoclasts
      - Crucial 'Human Osteoclastology'.
AB  - Osteoclasts play a critical role in both normal bone metabolism and bone
      resorption in the joints of patients with rheumatoid arthritis. It has been
      reported that non-steroidal anti-inflammatory drugs (NSAIDs) inhibit murine
      osteoclastogenesis in vitro and murine arthritis models in vivo, but not the
      destruction of joints of patients with rheumatoid arthritis. In the current
      review article, we review the recent findings in the effect of NSAIDs on the
      formation and function of human and murine osteoclasts both in vitro and in vivo,
      underlining the importance of studies using human osteoclasts. Since 2009, we
      have suggested a novel term 'human osteoclastology'.

PMID- 27713311
TI  - Natural Products in Epilepsy-the Present Situation and Perspectives for the
      Future.
AB  - More efficacious and better tolerated treatments for epilepsy are clearly needed.
      Complementary and alternative medicine (CAM) has a long history of use in certain
      parts of the world and has gained increasing interest over the last decades in
      Western countries. In countries with a Western-based type of medical system,
      people with epilepsy (PWE) take natural products or engage in other forms of CAM
      mainly to enhance general health, but also to prevent seizures or to alleviate
      symptoms of comorbidities or side effects of antiepileptic medications. In other
      countries, well developed medical systems, such as traditional Chinese Medicine
      and Ayurveda, are often the basis for treating PWE. Based on anecdotal reports of
      efficacy in PWE, natural products from these and other traditions are
      increasingly being studied in animal models of epilepsy, and candidates for
      further clinical development have been identified. It is likely, therefore, that
      natural products will be further evaluated for safety, tolerability and efficacy
      in PWE with drug-resistant seizures.

PMID- 27713310
TI  - Acid-Sensing Ion Channels and Pain.
AB  - Pathophysiological conditions such as inflammation, ischemia, infection and
      tissue injury can all evoke pain, and each is accompanied by local acidosis. Acid
      sensing ion channels (ASICs) are proton-gated cation channels expressed in both
      central and peripheral nervous systems. Increasing evidence suggests that ASICs
      represent essential sensors for tissue acidosis-related pain. This review
      provides an update on the role of ASICs in pain sensation and discusses their
      therapeutic potential for pain management.

PMID- 27713312
TI  - Suppression of Autoimmune Arthritis by Small Molecule Inhibitors of the JAK/STAT
      Pathway.
AB  - A skewed ratio of pro-inflammatory to anti-inflammatory cytokines, elevated
      growth factor synthesis and T- and B-lymphocyte activation are 3 hallmarks of
      rheumatoid arthritis (RA) pathology. Interleukin-6 (IL-6), IL-7, IL-17, IL-12/IL
      23 and growth factors, granulocyte macrophage-colony stimulating factor, IL-3,
      and erythropoietin activate the Janus Kinase/Signal Transducers and Activators of
      Transcription (JAK/STAT) pathway. Evidence showed that STAT protein
      phosphorylation (p-STAT) by activated JAKs is permissive for p-STAT to act as
      transcription factors by binding to STAT-responsive gene promoter sequences. This
      event is critical for perpetuating RA, in part, by up-regulating pro-inflammatory
      cytokine gene transcription. Activation of JAK/STAT by cytokines and growth
      factors can induce 'cross-talk' with other signaling pathways by which Stress
      Activated Protein/Mitogen-Activated Protein Kinase (SAP/MAPK) and
      Phosphatidylinositide-3-Kinase (PI3K)-mediated signaling are also activated. JAK
      specific small molecule inhibitors (SMIs) were developed to test whether JAK/STAT
      pathway blockade would regulate autoimmune-mediated inflammation. JAK-specific
      SMI blockade inhibited p-STAT induced by pro-inflammatory cytokines in vitro.
      Systemically administered JAK-specific SMI blockade also ameliorated biomarkers
      of inflammation in well-validated arthritis animal models. A few JAK-specific
      SMIs have made their way into RA clinical trials. In fact, the JAK3-specific SMI,
      CP-690,500 is the first JAK/STAT SMI to be assessed for clinical efficacy in a
      Phase III RA trial.

PMID- 27713314
TI  - Critical Overview on the Benefits and Harms of Aspirin.
AB  - Aspirin is widely used internationally for a variety of indications, with the
      most prominent one being that of cardiovascular disease. However, aspirin has
      also been proposed as a treatment option in a diverse range of conditions such as
      diabetes mellitus, cancer prevention, and obstetrics. In our overview, we
      critically appraise the current evidence from recent systematic reviews and meta
      analyses covering the benefits of aspirin across these conditions. We also look
      at evidence that some patients may not derive benefit due to the concept of
      aspirin resistance. Aspirin is also associated with the potential for significant
      harm, principally from haemorrhagic adverse events. We critically appraise the
      threat of haemorrhagic complications, and weigh up these risks against that of
      any potential benefit.

PMID- 27713313
TI  - Building Cell Selectivity into CPP-Mediated Strategies.
AB  - There is a pressing need for more effective and selective therapies for cancer
      and other diseases. Consequently, much effort is being devoted to the development
      of alternative experimental approaches based on selective systems, which are
      designed to be specifically directed against target cells. In addition, a large
      number of highly potent therapeutic molecules are being discovered. However, they
      do not reach clinical trials because of their low delivery, poor specificity or
      their incapacity to bypass the plasma membrane. Cell-penetrating peptides (CPPs)
      are an open door for cell-impermeable compounds to reach intracellular targets.
      Putting all these together, research is sailing in the direction of the design of
      systems with the capacity to transport new drugs into a target cell. Some CPPs
      show cell type specificity while others require modifications or form part of
      more sophisticated drug delivery systems. In this review article we summarize
      several strategies for directed drug delivery involving CPPs that have been
      reported in the literature.

PMID- 27713315
TI  - Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi
      faceted Anti-Tumor Modalities.
AB  - Photodynamic therapy (PDT) has emerged as one of the important therapeutic
      options in the management of cancer and other diseases. PDT involves a tumor
      localized photosensitizer (PS), which when appropriately illuminated by visible
      light converts oxygen into cytotoxic reactive oxygen species (ROS), that attack
      key structural entities within the targeted cells, ultimately resulting in
      necrosis or apoptosis. Though PDT is a selective modality, it can be further
      enhanced by combining other targeted therapeutic strategies that include the use
      of synthetic peptides and nanoparticles for selective delivery of
      photosensitizers. Another potentially promising strategy is the application of
      targeted therapeutics that exploit a myriad of critical pathways involved in
      tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor
      vasculature during PDT and anti-angiogenic agents that targets specific molecular
      pathways and prevent the formation of new blood vessels are novel therapeutic
      approaches that have been shown to improve treatment outcome. In addition to the
      well-documented mechanisms of direct cell killing and damage to the tumor
      vasculature, PDT can also activate the body's immune response against tumors.
      Numerous pre-clinical studies and clinical observations have demonstrated the
      immuno-stimulatory capability of PDT. Herein, we aim to integrate the most
      important findings with regard to the combination of PDT and other novel targeted
      therapy approaches, detailing its potential in cancer photomedicine.

PMID- 27713317
TI  - The Role of Non-Steroidal Anti-Inflammatory Drugs in the Chemoprevention of
      Breast Cancer.
AB  - Epidemiological evidence suggests that non-steroidal anti-inflammatory drugs
      (NSAIDs) which act as cyclooxygenase (COX-2) inhibitors may reduce breast cancer
      incidence by up to 20%. These agents are often taken for pain relief by older
      women with osteoarthritis. Age is the major risk factor for breast cancer in
      women with 50% cases being diagnosed in those aged >65 years. NSAIDs reduce serum
      estradiol by 17% in post-menopausal women and since most of these who develop
      breast cancers have estrogen receptor positive tumours; this suggests a possible
      preventative role. Careful use of these agents could provide a strategy for both
      relief of symptoms of osteoarthritis and also breast cancer prevention. Instead
      of conducting a randomised trial, proof of efficacy could be from an adequately
      powered cohort study within the breast screening programme.

PMID- 27713316
TI  - Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Progress in Small Molecule Drug
      Development.
AB  - Ever since the discovery of aspirin, small molecule therapeutics have been widely
      prescribed to treat inflammation and pain. Aspirin and several small molecule
      NSAIDs are known to inhibit the enzymes cyclooxygenase-1 (COX-1) and -2 (COX-2).
      Despite the success of NSAIDs to treat inflammatory disorders, the development of
      a clinically useful small molecule NSAIDs with decreased side effect profiles is
      an ongoing effort. The recent discovery and development of selective COX-2
      inhibitors was a step toward this direction. Emerging trends are represented by
      the progress in the development of hybrid agents such as nitric oxide donor
      NSAIDs (NO-NSAIDs) and dual COX/lipoxygenase (LOX) inhibitors. This review
      focuses on the recent advances in the rational design of small molecule NSAIDs in
      therapy.

PMID- 27713318
TI  - Chemoprophylaxis of Tropical Infectious Diseases.
AB  - Travelers to tropical countries are at risk for a variety of infectious diseases.
      In some cases effective vaccinations are available, but for other infections
      chemoprophylaxis can be offered. Malaria prevention has become increasingly
      complex as Plasmodium species become resistant to available drugs. In certain
      high risk settings, antibiotics can be used to prevent leptospirosis, scrub
      typhus and other infections. Post-exposure prophylaxis is appropriate for
      selected virulent infections. In this article the evidence for chemoprophylaxis
      will be reviewed.

PMID- 27713321
TI  - Beyond Genetics-Stratified and Personalised Medicines Using Multiple Parameters.
AB  - Prescribers have been practicing stratified medicine for many years. Patient
      characteristics, usually non-genetic, including age, comorbidities and
      concomitant medications are taken into account when deciding which drug to
      prescribe. In addition, the majority of drugs require dose adjustments across
      patient subgroups, usually determined by non-genetic differences between the
      subgroups. Whilst pharmacogenetics hold promise for enhancing treatment
      stratification and even treatment individualisation, non-genetic factors will
      continue to be very important. Both non-genetic and genetic factors must be
      considered to improve understanding and quantification of the variability in
      treatment outcomes and to guide stratification and targeting of patient subgroups
      to the right drug and also to the right range of doses within that subgroup.
      Development of stratified medicines must consider non-genetic as well as genetic
      factors and, where appropriate, include stratification through optimising the
      dose for each patient or subgroup as well as by choosing the drug most likely to
      deliver efficacy to that patient or group.

PMID- 27713319
TI  - NSAIDs, Mitochondria and Calcium Signaling: Special Focus on Aspirin/Salicylates.
AB  - Aspirin (acetylsalicylic acid) is a well-known nonsteroidal anti-inflammatory
      drug (NSAID) that has long been used as an anti-pyretic and analgesic drug.
      Recently, much attention has been paid to the chemopreventive and apoptosis
      inducing effects of NSAIDs in cancer cells. These effects have been thought to be
      primarily attributed to the inhibition of cyclooxygenase activity and
      prostaglandin synthesis. However, recent studies have demonstrated unequivocally
      that certain NSAIDs, including aspirin and its metabolite salicylic acid, exert
      their anti-inflammatory and chemopreventive effects independently of
      cyclooxygenase activity and prostaglandin synthesis inhibition. It is becoming
      increasingly evident that two potential common targets of NSAIDs are mitochondria
      and the Ca2+ signaling pathway. In this review, we provide an overview of the
      current knowledge regarding the roles of mitochondria and Ca2+ in the apoptosis
      inducing effects as well as some side effects of aspirin, salicylates and other
      NSAIDs, and introducing the emerging role of L-type Ca2+ channels, a new Ca2+
      entry pathway in non-excitable cells that is up-regulated in human cancer cells.

PMID- 27713320
TI  - Molecular Mechanism for Various Pharmacological Activities of NSAIDS.
AB  - The anti-inflammatory action of non-steroidal anti-inflammatory drugs (NSAIDs) is
      mediated through their inhibitory effects on cyclooxygenase (COX) activity. On
      the other hand, NSAID use is often associated with gastrointestinal
      complications. The inhibition of COX by NSAIDs is not the sole explanation for
      the gastrointestinal side effects of NSAIDs. Furthermore, recent epidemiological
      studies have revealed that prolonged NSAID use reduces the risk of cancer and
      Alzheimer's disease (AD) and a COX-independent unknown mechanism is suggested to
      be involved in these activities of NSAIDs. In this article, I review our recent
      work on the COX-independent mechanism involved in NSAID-induced gastric lesions
      and anti-tumor and anti-AD activities of NSAIDs. Using DNA microarray analysis,
      we found that NSAIDs affect expression of various genes in a COX-independent
      manner. We found that membrane permeabilization activity of NSAIDs and resulting
      NSAID-induced apoptosis are involved in NSAID-induced gastric lesions. On the
      other hand, induction of expression of tight junction-related genes and
      endoplasmic reticulum chaperones were suggested to be involved in anti-tumor and
      anti-AD, respectively, activities of NSAIDs. These results suggest that NSAIDs
      affect expression of various genes in a COX-independent manner, which is involved
      in various pharmacological activities of NSAIDs.

PMID- 27713322
TI  - NSAIDs: Old Drugs Reveal New Anticancer Targets.
AB  - There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs)
      and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but
      toxicity from cyclooxygenase (COX) inhibition and the suppression of
      physiologically important prostaglandins limits their use for cancer
      chemoprevention. Previous studies as reviewed here suggest that the mechanism for
      their anticancer properties does not require COX inhibition, but instead involves
      an off-target effect. In support of this possibility, recent molecular modeling
      studies have shown that the NSAID sulindac can be chemically modified to
      selectively design out its COX-1 and COX-2 inhibitory activity. Unexpectedly,
      certain derivatives that were synthesized based on in silico modeling displayed
      increased potency to inhibit tumor cell growth. Other experiments have shown that
      sulindac can inhibit phosphodiesterase to increase intracellular cyclic GMP
      levels and that this activity is closely associated with its ability to
      selectively induce apoptosis of tumor cells. Together, these studies suggest that
      COX-independent mechanisms can be targeted to develop safer and more efficacious
      drugs for cancer chemoprevention.

PMID- 27713325
TI  - Cobalt Complexes as Antiviral and Antibacterial Agents.
AB  - Metal ion complexes are playing an increasing role in the development of
      antimicrobials. We review here the antimicrobial properties of cobalt
      coordination complexes in oxidation state 3+. In addition to reviewing the cobalt
      complexes containing polydentate donor ligands, we also focus on the
      antimicrobial activity of the homoleptic [Co(NH3)6]3+ ion.

PMID- 27713326
TI  - The Role of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in the Management of
      the Post-Embolization Symptoms after Uterine Artery Embolization.
AB  - Uterine artery embolization (UAE) is usually a very painful procedure. Although
      pain after the procedure can occur as a single symptom, it usually is associated
      with other symptoms such as nausea, vomiting, pelvic pain, general malaise, fever
      and leukocytosis that characterize the post-embolization syndrome. Management of
      the post-embolization symptoms and of pain in particular, is paramount if UAE is
      to be performed as an outpatient procedure. Different protocols have used
      analgesic and/or anti-inflammatory agents to control these symptoms. Nonsteroidal
      anti-inflammatory drugs (NSAIDs) are frequently used in association with
      analgesic drugs to control post-embolization symptoms. In our institution the
      patients start oral medication with NSAIDs the day before the procedure and
      continue it during and after UAE. We also mix NSAIDs with the embolizing
      particles. This enables a reduction in the inflammation present in the uterine
      fibroids and helps controlling the pain. The purpose of this paper is to review
      the importance of NSAIDs in the management of the post-embolization symptoms. We
      describe the protocol that we use in our institution that enables us to perform
      the procedure on an outpatient basis with same day discharge and good control of
      the post-embolization symptoms with oral NSAIDs and analgesics.

PMID- 27713323
TI  - Effect of Non-Steroidal Anti-Inflammatory Drugs on Bone Healing.
AB  - Nonspecific and COX-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs)
      function by inhibiting the cyclooxygenase isoenzymes and effectively reduce pain
      and inflammation attributed to acute or chronic musculoskeletal pathologies.
      However, use of NSAIDs as an analgesic is thought to negatively contribute to
      bone healing. This review strived to provide a thorough unbiased analysis of the
      current research conducted on animals and humans regarding NSAIDs and their
      effect on bone healing. Specifically, this review discusses the role of animal
      models, dosing regiments, and outcome parameters when examining discrepancies
      about NSAIDS and their effects on bone regeneration. The role of COX-2 in bone
      regeneration needs to be better defined in order to further elucidate the impact
      of NSAIDs on bone healing.

PMID- 27713324
TI  - Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and
      the Host Innate Immune System.
AB  - In general antibiotics interact cooperatively with host defences, weakening and
      decreasing the virulence of microbial pathogens, thereby increasing vulnerability
      to phagocytosis and eradication by the intrinsic antimicrobial systems of the
      host. Antibiotics, however, also interact with host defences by several other
      mechanisms, some harmful, others beneficial. Harmful activities include
      exacerbation of potentially damaging inflammatory responses, a property of cell
      wall targeted agents, which promotes the release of pro-inflammatory microbial
      cytotoxins and cell-wall components. On the other hand, inhibitors of bacterial
      protein synthesis, especially macrolides, possess beneficial anti
      inflammatory/cytoprotective activities, which result from interference with the
      production of microbial virulence factors/cytotoxins. In addition to these
      pathogen-directed, anti-inflammatory activities, some classes of antimicrobial
      agent possess secondary anti-inflammatory properties, unrelated to their
      conventional antimicrobial activities, which target cells of the innate immune
      system, particularly neutrophils. This is a relatively uncommon, potentially
      beneficial property of antibiotics, which has been described for macrolides,
      imidazole anti-mycotics, fluoroquinolones, and tetracyclines. Although of largely
      unproven significance in the clinical setting, increasing awareness of the pro
      inflammatory and anti-inflammatory properties of antibiotics may contribute to a
      more discerning and effective use of these agents.

PMID- 27713327
TI  - Opportunities to Target Specific Contractile Abnormalities with Smooth Muscle
      Protein Kinase Inhibitors.
AB  - Smooth muscle is a major component of most hollow organ systems (e.g., airways,
      vasculature, bladder and gut/gastrointestine); therefore, the coordinated
      regulation of contraction is a key property of smooth muscle. When smooth muscle
      functions normally, it contributes to general health and wellness, but its
      dysfunction is associated with morbidity and mortality. Rho-associated protein
      kinase (ROCK) is central to calcium-independent, actomyosin-mediated contractile
      force generation in the vasculature, thereby playing a role in smooth muscle
      contraction, cell motility and adhesion. Recent evidence supports an important
      role for ROCK in the increased vasoconstriction and remodeling observed in
      various models of hypertension. This review will provide a commentary on the
      development of specific ROCK inhibitors and their clinical application. Fasudil
      will be discussed as an example of bench-to-bedside development of a clinical
      therapeutic that is used to treat conditions of vascular hypercontractility. Due
      to the wide spectrum of biological processes regulated by ROCK, many additional
      clinical indications might also benefit from ROCK inhibition. Apart from the
      importance of ROCK in smooth muscle contraction, a variety of other protein
      kinases are known to play similar roles in regulating contractile force. The
      zipper-interacting protein kinase (ZIPK) and integrin-linked kinase (ILK) are two
      well-described regulators of contraction. The relative contribution of each
      kinase to contraction depends on the muscle bed as well as hormonal and neuronal
      stimulation. Unfortunately, specific inhibitors for ZIPK and ILK are still in the
      development phase, but the success of fasudil suggests that inhibitors for these
      other kinases may also have valuable clinical applications. Notably, the directed
      inhibition of ZIPK with a pseudosubstrate molecule shows unexpected effects on
      the contractility of gastrointestinal smooth muscle.

PMID- 27713328
TI  - Aptamers for Targeted Drug Delivery.
AB  - Aptamers are a class of therapeutic oligonucleotides that form specific three
      dimensional structures that are dictated by their sequences. They are typically
      generated by an iterative screening process of complex nucleic acid libraries
      employing a process termed Systemic Evolution of Ligands by Exponential
      Enrichment (SELEX). SELEX has traditionally been performed using purified
      proteins, and cell surface receptors may be challenging to purify in their
      properly folded and modified conformations. Therefore, relatively few aptamers
      have been generated that bind cell surface receptors. However, improvements in
      recombinant fusion protein technology have increased the availability of receptor
      extracellular domains as purified protein targets, and the development of cell
      based selection techniques has allowed selection against surface proteins in
      their native configuration on the cell surface. With cell-based selection, a
      specific protein target is not always chosen, but selection is performed against
      a target cell type with the goal of letting the aptamer choose the target.
      Several studies have demonstrated that aptamers that bind cell surface receptors
      may have functions other than just blocking receptor-ligand interactions. All
      cell surface proteins cycle intracellularly to some extent, and many surface
      receptors are actively internalized in response to ligand binding. Therefore,
      aptamers that bind cell surface receptors have been exploited for the delivery of
      a variety of cargoes into cells. This review focuses on recent progress and
      current challenges in the field of aptamer-mediated delivery.

PMID- 27713329
TI  - The Pharmacogenomics of Anti-Hypertensive Therapy.
AB  - Hypertension is a major public health problem, but measures to reduce blood
      pressure and thus cardiovascular risk are complicated by the high prevalence of
      treatment resistance, despite the availability of multiple drugs. Drug side
      effects contribute considerably to suboptimal blood pressure control. Clinicians
      must often rely on empirical methods to match patients with effective drug
      treatment. Hypertension pharmacogenomics seeks to find genetic predictors of
      response to drugs that lower blood pressure and to translate this knowledge into
      clinical practice. In this review we summarise the current status of hypertension
      pharmacogenetics from monogenic hypertension to essential hypertension and
      discuss the issues that need to be considered in a hypertension pharmacogenomic
      study.

PMID- 27713330
TI  - Role of Leukotrienes and Leukotriene Modifiers in Asthma.
AB  - Leukotrienes (LTs), including cysteinyl LTs (CysLTs) and LTB4, are potent lipid
      mediators that are pivotal in the pathophysiology of asthma phenotypes. At least
      two receptor subtypes for CysLTs - CysLT1 and CysLT2 - have been identified. Most
      of the pathophysiological effects of CysLTs in asthma, including increased airway
      smooth muscle activity, microvascular permeability and airway mucus secretion,
      are mediated by the activation of the CysLT1 receptor. LTB4 may have a role in
      the development of airway hyperresponsiveness, severe asthma and asthma
      exacerbations. Although generally less effective than inhaled glucocorticoids,
      CysLT1 receptor antagonists can be given orally as monotherapy in patients with
      persistent mild asthma. In patients with more severe asthma, CysLT1 receptor
      antagonists can be combined with inhaled glucocorticoids. This therapeutic
      strategy improves asthma control and enables the dose of inhaled glucocorticoids
      to be reduced, while maintaining similar efficacy. The identification of
      subgroups of patients with asthma who respond to CysLT1 receptor antagonists is
      relevant for asthma management, as the response to these drugs is variable. The
      potential anti-remodeling effect of CysLT1 receptor antagonists might be
      important for preventing or reversing airway structural changes in patients with
      asthma. This review discusses the role of LTs in asthma and the therapeutic
      implications of the pharmacological modulation of the LT pathway for asthma.

PMID- 27713333
TI  - In Response to: 'Impact of Glycosylation on Effector Functions of Therapeutic
      IgG' (Pharmaceuticals 2010, 3, 146-157).
AB  - To complete the review article by Abes and colleagues (Pharmaceuticals 2010, 3,
      146-157) which provides a good overview on recently developed approaches for
      generation of glyco-modified antibodies and the impact of glyco-modification of
      antibodies on their effector functions, important information should be added,
      namely that - besides the Glycart and the Biowa approach to generate de
      fucosylated antibodies - innovative, moss derived methods have been shown to
      generate glyco-modified antibodies with improved effector function profile.

PMID- 27713332
TI  - Use of p38 MAPK Inhibitors for the Treatment of Werner Syndrome.
AB  - Werner syndrome provides a convincing model for aspects of the normal ageing
      phenotype and may provide a suitable model for therapeutic interventions designed
      to combat the ageing process. Cultured primary fibroblast cells from Werner
      syndrome patients provide a powerful model system to study the link between
      replicative senescence in vitro and in vivo pathophysiology. Genome instability,
      together with an increased pro-oxidant state, and frequent replication fork
      stalling, all provide plausible triggers for intracellular stress in Werner
      syndrome cells, and implicates p38 MAPK signaling in their shortened replicative
      lifespan. A number of different p38 MAPK inhibitor chemotypes have been prepared
      rapidly and efficiently using microwave heating techniques for biological study
      in Werner syndrome cells, including SB203580, VX-745, RO3201195, UR-13756 and
      BIRB 796, and their selectivity and potency evaluated in this cellular context.
      Werner syndrome fibroblasts treated with a p38 MAPK inhibitor reveal an
      unexpected reversal of the accelerated ageing phenotype. Thus the study of p38
      inhibition and its effect upon Werner pathophysiology is likely to provide new
      revelations into the biological mechanisms operating in cellular senescence and
      human ageing in the future.

PMID- 27713334
TI  - A Review of Topical Diclofenac Use in Musculoskeletal Disease.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed medications
      for the treatment of musculoskeletal disorders. Osteoarthritis is the most common
      form of arthritis in humans and its prevalence rises with age. Oral NSAIDs have
      potential associated toxicities that must be monitored for and can limit the use
      of these drugs in certain populations including people of older age. Topical
      NSAIDs are now being recognized as an option for the treatment strategy of
      osteoarthritis. We review the efficacy and safety of one of the most common
      topical NSAIDS, topical diclofenac, for the treatment of osteoarthritis.

PMID- 27713331
TI  - Non-Steroidal Anti-Inflammatory Drugs in Alzheimer's Disease and Parkinson's
      Disease: Reconsidering the Role of Neuroinflammation.
AB  - Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common
      neurodegenerative diseases with age as the greatest risk factor. As the general
      population experiences extended life span, preparation for the prevention and
      treatment of these and other age-associated neurological diseases are warranted.
      Since epidemiological studies suggested that non-steroidal anti-inflammatory drug
      (NSAID) use decreased risk for AD and PD, increasing attention has been devoted
      to understanding the costs and benefits of the innate neuroinflammatory response
      to functional recovery following pathology onset. This review will provide a
      general overview on the role of neuroinflammation in these neurodegenerative
      diseases and an update on NSAID treatment in recent experimental animal models,
      epidemiological analyses, and clinical trials.

PMID- 27713335
TI  - Unlocking the Door to Neuronal Woes in Alzheimer's Disease: Abeta and
      Mitochondrial Permeability Transition Pore.
AB  - Mitochondrial dysfunction occurs early in the progression of Alzheimer's disease.
      Amyloid-beta peptide has deleterious effects on mitochondrial function and
      contributes to energy failure, respiratory chain impairment, neuronal apoptosis,
      and generation of reactive oxygen species in Alzheimer's disease. The mechanisms
      underlying amyloid-beta induced mitochondrial stress remain unclear. Emerging
      evidence indicates that mitochondrial permeability transition pore is important
      for maintenance of mitochondrial and neuronal function in aging and
      neurodegenerative disease. Cyclophilin D (Cyp D) plays a central role in opening
      mitochondrial permeability transition pores, ultimately leading to cell death.
      Interaction of amyloid-beta with cyclophilin D triggers or enhances the formation
      of mitochondrial permeability transition pores, consequently exacerbating
      mitochondrial and neuronal dysfunction, as shown by decreased mitochondrial
      membrane potential, impaired mitochondrial respiration function, and increased
      oxidative stress and cytochrome c release. Blockade of cyclophilin D by genetic
      abrogation or pharmacologic inhibition protects mitochondria and neurons from
      amyloid-beta induced toxicity, suggesting that cyclophilin D dependent
      mitochondrial transition pores are a therapeutic target for Alzheimer's disease.

PMID- 27713336
TI  - Non-Steroidal Anti-Inflammatory Drugs and Brain Inflammation: Effects on
      Microglial Functions.
AB  - The term NSAID refers to structurally diverse chemical compounds that share the
      ability to inhibit the activity of the prostaglandin (PG) biosynthetic enzymes,
      the cyclooxygenase (COX) isoforms 1 and 2. The suppression of PG synthesis at
      sites of inflammation has been regarded as primarily responsible for the
      beneficial properties of NSAIDs, but several COX-independent effects have been
      described in recent years. Epidemiological studies indicate that NSAIDs are
      neuroprotective, although the mechanisms underlying their beneficial effect
      remain largely unknown. Microglial cells play a major role in brain inflammation
      and are often viewed as major contributors to the neurodegeneration. Therefore,
      microglia represent a likely target for NSAIDs within the brain. In the present
      review, we focused on the direct effects of NSAIDs and selective COX-2 inhibitors
      on microglial functions and discuss the potential efficacy in controlling brain
      inflammation.

PMID- 27713338
TI  - Linezolid Resistance in Staphylococci.
AB  - Linezolid, the first oxazolidinone to be used clinically, is effective in the
      treatment of infections caused by various Gram-positive pathogens, including
      multidrug resistant enterococci and methicillin-resistant Staphylococus aureus.
      It has been used successfully for the treatment of patients with endocarditis and
      bacteraemia, osteomyelitis, joint infections and tuberculosis and it is often
      used for treatment of complicated infections when other therapies have failed.
      Linezolid resistance in Gram-positive cocci has been encountered clinically as
      well as in vitro, but it is still a rare phenomenon. The resistance to this
      antibiotic has been, until now, entirely associated with distinct nucleotide
      substitutions in domain V of the 23S rRNA genes. The number of mutated rRNA genes
      depends on the dose and duration of linezolid exposure and has been shown to
      influence the level of linezolid resistance. Mutations in associated ribosomal
      proteins also affect linezolid activity. A new phenicol and clindamycin
      resistance phenotype has recently been found to be caused by an RNA
      methyltransferase designated Cfr. This gene confers resistance to lincosamides,
      oxazolidinones, streptogramin A, phenicols and pleuromutilins, decrease the
      susceptibility of S. aureus to tylosin, to josamycin and spiramycin and thus
      differs from erm rRNA methylase genes. Research into new oxazolidinones with
      improved characteristics is ongoing. Data reported in patent applications
      demonstrated that some oxazolidinone derivatives, also with improved
      characteristics with respect to linezolid, are presently under study: at least
      three of them are in an advanced phase of development.

PMID- 27713337
TI  - NSAIDs in the Acute Treatment of Migraine: A Review of Clinical and Experimental
      Data.
AB  - Migraine is a common disabling neurological disorder with a serious socio
      economical burden. By blocking cyclooxygenase nonsteroidal anti-inflammatory
      drugs (NSAIDs) decrease the synthesis of prostaglandins, which are involved in
      the pathophysiology of migraine headaches. Despite the introduction more than a
      decade ago of a new class of migraine-specific drugs with superior efficacy, the
      triptans, NSAIDs remain the most commonly used therapies for the migraine attack.
      This is in part due to their wide availability as over-the-counter drugs and
      their pharmaco-economic advantages, but also to a favorable efficacy/side effect
      profile at least in attacks of mild and moderate intensity. We summarize here
      both the experimental data showing that NSAIDs are able to influence several
      pathophysiological facets of the migraine headache and the clinical studies
      providing evidence for the therapeutic efficacy of various subclasses of NSAIDs
      in migraine therapy. Taken together these data indicate that there are several
      targets for NSAIDs in migraine pathophysiology and that on the spectrum of
      clinical potency acetaminophen is at the lower end while ibuprofen is among the
      most effective drugs. Acetaminophen and aspirin excluded, comparative trials
      between the other NSAIDs are missing. Since evidence-based criteria are scarce,
      the selection of an NSAID should take into account proof and degree of efficacy,
      rapid GI absorption, gastric ulcer risk and previous experience of each
      individual patient. If selected and prescribed wisely, NSAIDs are precious, safe
      and cost-efficient drugs for the treatment of migraine attacks.

PMID- 27713339
TI  - NSAIDs and Cell Proliferation in Colorectal Cancer.
AB  - Colon cancer is common worldwide and accounts for significant morbidity and
      mortality in patients. Fortunately, epidemiological studies have demonstrated
      that continuous therapy with NSAIDs offers real promise of chemoprevention and
      adjunct therapy for colon cancer patients. Tumour growth is the result of complex
      regulation that determines the balance between cell proliferation and cell death.
      How NSAIDs affect this balance is important for understanding and improving
      treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and
      impair the growth of colon cancer cell lines when tested in culture in vitro and
      many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models
      and in patients, but the relationship to inhibition of tumour cell proliferation
      is less convincing, principally due to gaps in the available data. High
      concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition
      and growth retardation at varying time-points following treatment. However, the
      results from studies with colon cancer cell xenografts are promising and,
      together with better comparative data on anti-proliferative NSAID concentrations
      and doses (for in vitro and in vivo administration), could provide more
      information to improve our understanding of the relationships between these
      agents, dose and dosing regimen, and cellular environment.

PMID- 27713341
TI  - Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4
      Lymphoma Cells.
AB  - Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of
      phosphatidylcholine. PLD2 has been shown to play a role in enhancing
      tumorigenesis. The epidermal growth factor receptor (EGFR) can both activate and
      interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a
      unique model to elucidate the role of PLD2 in signal transduction. In the current
      study, we investigated effects of PLD2 on EGF response. Western blotting and RT
      PCR were used to establish that both parental cells and PLD2 transfectants
      express endogenous EGFR. Levels of EGFR protein are increased in cells expressing
      active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF
      stimulates proliferation of EL4 cells transfected with active PLD2, but not
      parental cells or cells transfected with inactive PLD2. EGF-mediated
      proliferation in cells expressing active PLD2 is dependent on the activities of
      both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein
      kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix
      is enhanced in cells expressing active PLD2, as compared to parental cells or
      cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts
      in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

PMID- 27713340
TI  - Demethylating Agents in the Treatment of Cancer.
AB  - Gene silencing resulting from aberrant DNA methylation can lead to tumorigenesis.
      Therefore, drugs that inhibit or interfere with DNA methylation have been used to
      reactivate and induce silenced gene re-expression in malignancies. Two
      demethylating agents, azacitidine and decitabine, are approved for the treatment
      of myelodysplastic syndromes (MDS) by the U.S. Food and Drug Administration
      (FDA), and are now considered the standard of care in MDS. In this review, we
      discuss clinical data, including clinical benefits and toxicities, which led to
      the approval of azacitidine and decitabine. We also summarize findings from
      clinical trials that used these two demethylating agents in the treatment of
      solid tumors. Lastly, we discuss some limitations in the use of azacitidine and
      decitabine in cancer therapy.

PMID- 27713343
TI  - Role of Non-Steroidal Anti-Inflammatory Drugs in Gynecology.
AB  - This review summarizes the current use of non-steroidal anti-inflammatory drugs
      (NSAIDs) in obstetrics, gynecology and infertility. These medications are
      commonly used in different fields of reproductive medicine, for pain management
      after operative procedures and to relieve dysmenorrhea. In addition to their
      analgesic effect, NSAIDs are helpful in the management of menorrhagia by
      decreasing menstrual blood loss. NSAIDs alleviate pain associated with medical
      abortion, assist in undertaking natural cycle in-vitro fertilization by
      preventing follicular rupture and reducing premature ovulation, and serve as
      tocolytics in preterm labor. New NSAIDs may have a growing role in management of
      women's health.

PMID- 27713342
TI  - In Silico Screening of Nonsteroidal Anti-Inflammatory Drugs and Their Combined
      Action on Prostaglandin H Synthase-1.
AB  - The detailed kinetic model of Prostaglandin H Synthase-1 (PGHS-1) was applied to
      in silico screening of dose-dependencies for the different types of nonsteroidal
      anti-inflammatory drugs (NSAIDs), such as: reversible/irreversible,
      nonselective/selective to PGHS-1/PGHS-2 and time dependent/independent inhibitors
      (aspirin, ibuprofen, celecoxib, etc.) The computational screening has shown a
      significant variability in the IC50s of the same drug, depending on different in
      vitro and in vivo experimental conditions. To study this high heterogeneity in
      the inhibitory effects of NSAIDs, we have developed an in silico approach to
      evaluate NSAID action on targets under different PGHS-1 microenvironmental
      conditions, such as arachidonic acid, reducing cofactor, and peroxide
      concentrations. The designed technique permits translating the drug IC50,
      obtained in one experimental setting to another, and predicts in vivo inhibitory
      effects based on the relevant in vitro data. For the aspirin case, we elucidated
      the mechanism underlying the enhancement and reduction (aspirin resistance) of
      its efficacy, depending on PGHS-1 microenvironment in in vitro/in vivo
      experimental settings. We also present the results of the in silico screening of
      the combined action of sets of two NSAIDs (aspirin with ibuprofen, aspirin with
      celecoxib), and study the mechanism of the experimentally observed effect of the
      suppression of aspirin-mediated PGHS-1 inhibition by selective and nonselective
      NSAIDs. Furthermore, we discuss the applications of the obtained results to the
      problems of standardization of NSAID test assay, dependence of the NSAID efficacy
      on cellular environment of PGHS-1, drug resistance, and NSAID combination
      therapy.

PMID- 27713344
TI  - Difficulties in Treatment and Management of Epilepsy and Challenges in New Drug
      Development.
AB  - Epilepsy is a serious neurological disorder that affects around 50 million people
      worldwide. Almost 30% of epileptic patients suffer from pharmacoresistance, which
      is associated with social isolation, dependent behaviour, low marriage rates,
      unemployment, psychological issues and reduced quality of life. Currently
      available antiepileptic drugs have a limited efficacy, and their negative
      properties limit their use and cause difficulties in patient management.
      Antiepileptic drugs can provide only symptomatic relief as these drugs suppress
      seizures but do not have ability to cure epileptogenesis. The long term use of
      antiepileptic drugs is limited due to their adverse effects, withdrawal symptoms,
      deleterious interactions with other drugs and economic burden, especially in
      developing countries. Furthermore, some of the available antiepileptic drugs may
      even potentiate certain type of seizures. Several in vivo and in vitro animal
      models have been proposed and many new antiepileptic drugs have been marketed
      recently, but large numbers of patients are still pharmacoresistant. This review
      will highlight the difficulties in treatment and management of epilepsy and the
      limitations of available antiepileptic drugs and animal seizure models.

PMID- 27713346
TI  - Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks.
AB  - While aspirin may offer protection, other non-aspirin non-steroidal anti
      inflammatory drugs (NSAIDs) can cause serious cardiovascular side effects and
      complications. This has led to a general "black box" warning for cardiovascular
      adverse events for NSAIDs. This review explores the different mechanisms
      underlying the protective effects of aspirin, the NSAID associated renovascular
      effects causing hypertension, edema and heart failure, the cardiovascular effects
      causing myocardial infarction and stroke, and the possible deleterious
      interaction between NSAIDs and aspirin.

PMID- 27713347
TI  - Cannabinoid-Induced Hyperemesis: A Conundrum-From Clinical Recognition to Basic
      Science Mechanisms.
AB  - Cannabinoids are used clinically on a subacute basis as prophylactic agonist
      antiemetics for the prevention of nausea and vomiting caused by
      chemotherapeutics. Cannabinoids prevent vomiting by inhibition of release of
      emetic neurotransmitters via stimulation of presynaptic cannabinoid CB1
      receptors. Cannabis-induced hyperemesis is a recently recognized syndrome
      associated with chronic cannabis use. It is characterized by repeated cyclical
      vomiting and learned compulsive hot water bathing behavior. Although considered
      rare, recent international publications of numerous case reports suggest the
      contrary. The syndrome appears to be a paradox and the pathophysiological
      mechanism(s) underlying the induced vomiting remains unknown. Although some
      traditional hypotheses have already been proposed, the present review critically
      explores the basic science of these explanations in the clinical setting and
      provides more current mechanisms for the induced hyperemesis. These encompass:
      (1) pharmacokinetic factors such as long half-life, chronic exposure, lipid
      solubility, individual variation in metabolism/excretion leading to accumulation
      of emetogenic cannabinoid metabolites, and/or cannabinoid withdrawal; and (2)
      pharmacodynamic factors including switching of the efficacy of Delta8-THC from
      partial agonist to antagonist, differential interaction of Delta8-THC with Gs and
      Gi signal transduction proteins, CB1 receptor desensitization or downregulation,
      alterations in tissue concentrations of endocannabinoid agonists/inverse
      agonists, Delta8-THC-induced mobilization of emetogenic metabolites of the
      arachidonic acid cascade, brainstem versus enteric actions of Delta8-THC, and/or
      hypothermic versus hyperthermic actions of Delta8-THC. In addition, human and
      animal findings suggest that chronic exposure to cannabis may not be a
      prerequisite for the induction of vomiting but is required for the intensity of
      emesis.

PMID- 27713348
TI  - The Molecular Mechanisms of Anesthetic Action: Updates and Cutting Edge
      Developments from the Field of Molecular Modeling.
AB  - For over 160 years, general anesthetics have been given for the relief of pain
      and suffering. While many theories of anesthetic action have been purported, it
      has become increasingly apparent that a significant molecular focus of anesthetic
      action lies within the family of ligand-gated ion channels (LGIC's). These
      protein channels have a transmembrane region that is composed of a pentamer of
      four helix bundles, symmetrically arranged around a central pore for ion passage.
      While initial and some current models suggest a possible cavity for binding
      within this four helix bundle, newer calculations postulate that the actual
      cavity for anesthetic binding may exist between four helix bundles. In either
      scenario, these cavities have a transmembrane mode of access and may be partially
      bordered by lipid moieties. Their physicochemical nature is amphiphilic.
      Anesthetic binding may alter the overall motion of a ligand-gated ion channel by
      a "foot-in-door" motif, resulting in the higher likelihood of and greater time
      spent in a specific channel state. The overall gating motion of these channels is
      consistent with that shown in normal mode analyses carried out both in vacuo as
      well as in explicitly hydrated lipid bilayer models. Molecular docking and large
      scale molecular dynamics calculations may now begin to show a more exact mode by
      which anesthetic molecules actually localize themselves and bind to specific
      protein sites within LGIC's, making the design of future improvements to
      anesthetic ligands a more realizable possibility.

PMID- 27713345
TI  - Protein Kinases as Drug Development Targets for Heart Disease Therapy.
AB  - Protein kinases are intimately integrated in different signal transduction
      pathways for the regulation of cardiac function in both health and disease.
      Protein kinase A (PKA), Ca2+-calmodulin-dependent protein kinase (CaMK), protein
      kinase C (PKC), phosphoinositide 3-kinase (PI3K) and mitogen-activated protein
      kinase (MAPK) are not only involved in the control of subcellular activities for
      maintaining cardiac function, but also participate in the development of cardiac
      dysfunction in cardiac hypertrophy, diabetic cardiomyopathy, myocardial
      infarction, and heart failure. Although all these kinases serve as signal
      transducing proteins by phosphorylating different sites in cardiomyocytes, some
      of their effects are cardioprotective whereas others are detrimental. Such
      opposing effects of each signal transduction pathway seem to depend upon the
      duration and intensity of stimulus as well as the type of kinase isoform for each
      kinase. In view of the fact that most of these kinases are activated in heart
      disease and their inhibition has been shown to improve cardiac function, it is
      suggested that these kinases form excellent targets for drug development for
      therapy of heart disease.

PMID- 27713349
TI  - Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.
AB  - Cannabis contains the psychoactive component delta8-tetrahydrocannabinol (delta8
      THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and
      cannabigerol. It is well-known that delta8-THC and other cannabinoid CB1 receptor
      agonists are neuroprotective during global and focal ischemic injury.
      Additionally, delta8-THC also mediates psychological effects through the
      activation of the CB1 receptor in the central nervous system. In addition to the
      CB1 receptor agonists, cannabis also contains therapeutically active components
      which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the
      most important is CBD. In the past five years, an increasing number of
      publications have focused on the discovery of the anti-inflammatory, anti
      oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive
      pharmacological effects in ischemic stroke and other chronic diseases, including
      Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. The
      cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and
      has potent anti-oxidant activity. Importantly, CBD use does not lead to
      tolerance. In this review, we will discuss the therapeutic possibility of CBD as
      a cerebroprotective agent, highlighting recent pharmacological advances, novel
      mechanisms, and therapeutic time window of CBD in ischemic stroke.

PMID- 27713350
TI  - High-Dose Ibuprofen in Cystic Fibrosis.
AB  - Cystic Fibrosis (CF) is the most common lethal genetic disorder in North America
      and Europe. Most patients succumb to progressive lung disease characterized by an
      exaggerated neutrophilic inflammation. In animal models of chronic infection,
      high-dose ibuprofen was demonstrated to reduce inflammation without hindering
      bacterial clearance. This led to two clinical trials, which demonstrated a
      benefit in slowing the progression of lung disease in CF. However, concerns about
      potential adverse effects have limited the use of high-dose ibuprofen in CF
      patients. There are a variety of potential mechanisms to account for the observed
      clinical benefit. A better understanding of these mechanisms could potentially
      lead to more targeted and better-tolerated anti-inflammatory therapies.

PMID- 27713351
TI  - Nonsteroidal Anti-Inflammatory Drug-Induced Gastroduodenal Bleeding: Risk Factors
      and Prevention Strategies.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed
      medications in the World. A frequent complication of NSAID use is gastroduodenal
      bleeding. Risk factors for gastroduodenal bleeding while on NSAID therapy are
      age, prior peptic ulcer and co-medication with anti-platelet agents,
      anticoagulants, glucocorticosteroids and selective serotonin-reuptake inhibitors
      (SSRI). Prevention strategies for at-risk patients include the use of the lowest
      effective dose of NSAIDs, co-therapy with proton-pump inhibitors and/or the use
      of a COX-2 selective agent. Treatment of Helicobacter pylori infection is
      beneficial for primary prophylaxis of NSAID-induced gastroduodenal bleeding in
      NSAID-naive patients. For patients with cardiovascular risk factors requiring
      NSAIDs, naproxen should be selected. In very high risk patients for both
      gastrointestinal and cardiovascular complications NSAID therapy should be avoided
      altogether.

PMID- 27713352
TI  - EGFR Targeting in Hormone-Refractory Prostate Cancer: Current Appraisal and
      Prospects for Treatment.
AB  - The incidence of prostate cancer increases with age and because of its high
      prevalence this disease has become a major public health concern. Despite
      advances in our understanding of the biological mechanisms responsible for the
      development of this cancer, the transition to the hormone refractory stage (HRPC)
      and metastatic progression pose real problems of clinical management. Currently,
      docetaxel chemotherapy has been shown to have a slight but significant impact on
      survival, though the gain in median survival is still less than three months.
      Research is therefore continuing to improve treatment outcomes. The progression
      of prostate cancer is accompanied by the overexpression of EGFR (epidermal growth
      factor receptor) in a very large majority of cases, suggesting that this may play
      a mechanistic role. Unfortunately, although preclinical findings seem to be
      promising for therapies targeting the EGFR in HRPC, current clinical results are
      disappointing. These results should however encourage us to look for different
      ways of using anti-EGFR agents or combining them with other targeted therapies.

PMID- 27713353
TI  - Emerging Families of Ion Channels Involved in Urinary Bladder Nociception.
AB  - The expression of multiple ion channels and receptors is essential for
      nociceptors to detect noxious stimuli of a thermal, mechanical or chemical
      nature. The peripheral sensory transduction systems of the urinary bladder
      include sensory nerve endings, urothelial cells and others whose location is
      suitable for transducing mechanical and chemical stimuli. There is an increasing
      body of evidence implicating the Deg/ENaC and TRP channel families in the control
      of bladder afferent excitability under physiological and pathological conditions.
      Pharmacological interventions targeting these ion channels may provide a new
      strategy for the treatment of pathological bladder sensation and pain.

PMID- 27713355
TI  - Artesunate: The Best Drug in the Treatment of Severe and Complicated Malaria.
AB  - This review summarizes progress in treating severe and complicated malaria, which
      are global problems, claiming at least one million lives annually, and have been
      accompanied by advances in our understanding of the pathogenesis of severe
      malaria complications. New drugs such as intravenous artesunate (AS) and
      intramuscular artemether (AM) are improving outcomes and decreasing malaria
      deaths. Trials comparing AM to the traditional parenteral drug, quinine, have not
      demonstrated however convincing evidence of a mortality advantage for AM. The
      South East Asian Quinine Artesunate Malaria Trials (SEAQUAMAT), a multicenter,
      randomized, open-label study comparing AS with quinine showed that parenteral AS
      was shown to be associated with a 35% reduction in the risk of mortality compare
      to quinine, and is now the recommended treatment by the WHO for severe and
      complicated malaria in low-transmission areas and in the second and third
      trimesters of pregnancy, with almost all the benefit reported in those with high
      parasite counts. Artesunate is a semisynthetic derivative of artemisinin whose
      water solubility facilitates absorption and provides an advantage over other
      artemisinins because it can be formulated as oral, rectal, intramuscular, and
      intravenous preparations. Artesunate is rapidly hydrolyzed to dihydroartemisinin,
      which is the most active schizonticidal metabolite. Injectable AS results in a
      more rapid systemic availability of AS compared with intramuscular AM. This
      pharmacokinetic advantage may provide a clinical advantage in the treatments of
      severe and complicated malaria.

PMID- 27713354
TI  - Nonsteroidal Anti-Inflammatory Drugs and the Kidney.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and
      COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid
      and urinary electrolyte excretion) vary with the extent of COX-2-COX-1
      selectivity and the administered dose of these compounds. While young healthy
      subjects will rarely experience adverse renal effects with the use of NSAIDs,
      elderly patients and those with co-morbibity (e.g., congestive heart failure,
      liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin
      angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure.
      This review summarizes our present knowledge how traditional NSAIDs and selective
      COX-2 inhibitors may affect the kidney under various experimental and clinical
      conditions, and how these drugs may influence renal inflammation, water
      transport, sodium and potassium balance and how renal dysfunction or hypertension
      may result.

PMID- 27713357
TI  - Rational Polytherapy with Antiepileptic Drugs.
AB  - Approximately 30-40% of patients do not achieve seizure control with a single
      antiepileptic drug (AED). With the advent of multiple AEDs in the past 15 years,
      rational polytherapy, the goal of finding combinations of AEDs that have
      favorable characteristics, has become of greater importance. We review the
      theoretical considerations based on AED mechanism of action, animal models, human
      studies in this field, and the challenges in finding such optimal combinations.
      Several case scenarios are presented, illustrating examples of rational
      polytherapy.

PMID- 27713358
TI  - Rational Use of Antibiotics in the Treatment of Functional Bowel Disorders.
AB  - Functional gastrointestinal symptoms such us bloating, fullness, flatulence,
      diarrhea, and constipation due to irritable bowel syndrome (IBS) were recently
      attributed to small bowel bacterial overgrowth, a condition depending on the
      presence of an increased number of bacteria in the small bowel. However, the
      methodology used to describe this association may be harshly criticized, since it
      has already been shown to be quite inaccurate. As a result an inappropriate use
      of antibiotics was consequently generated. In fact, antibiotics could be
      effective in the treatment of functional complaints, but only in a limited
      subgroup of patients, characterized by an increase of fermentation at colonic
      level. In this review, we have examined the papers suggesting a
      pathophysiological link between IBS and small bowel bacterial overgrowth,
      underlining its inappropriateness, and put forth our personal view on the
      rationale for antibiotic use in IBS.

PMID- 27713359
TI  - Measurement of Neuropsychiatric Symptoms in Clinical Trials Targeting Alzheimer's
      Disease and Related Disorders.
AB  - Behavioral and psychological symptoms (BPSD) are now known to be frequently
      associated to cognitive and functional decline in Alzheimer's disease and related
      disorders. They are present since the early stages of the disease and have
      negative impact on the disease process. BPSD assessment is crucial in clinical
      practice and also in future clinical trials targeting disease-modifying therapies
      for dementia. In this article, we will first review current assessment tools for
      BPSD, mainly global and domain-specific scales, and new assessment methods,
      currently available or in development, including new scales, diagnostic criteria
      and new technologies such as ambulatory actigraphy.

PMID- 27713356
TI  - The Health Effect of Psychostimulants: A Literature Review.
AB  - Prevalence of psychostimulant use is high, and raising in several countries.
      Nicotine is the legal stimulant causing the most important public health impact.
      Cocaine ranks among the most used illicit substances after cannabis. Stimulant
      medications are frequently misused. Psychostimulants can lead to addiction, have
      physical, psychological and social health consequences and can induce a great
      disease burden. The aim of the present article is to provide a literature review
      on the health effects of stimulants as potential drugs of abuse. It will cover
      essentially cocaine, amphetamines and its derivatives (including methamphetamines
      and 3-4-methylenedioxymethamphetamine, ecstasy), nicotine, caffeine and khat, and
      touch upon the issues of prescribed substances (anti-depressants, weight control
      medications, attention-deficit hyperactivity disorder medications, hypersomniac
      disorder). Their pharmacology, addictive potential, health consequences and
      treatment will be discussed. We used Medline for the literature review from 1990
      to the date of this review, and mention the findings of human and animal studies
      (the latter only if they are of clinical relevance).

PMID- 27713361
TI  - Synthesis and Antimicrobial Activity of Some New Quinoxaline Derivatives.
AB  - 2-Chloro-3-methylquinoxaline was selected as a nucleus around which various
      molecular transformations were performed to obtain new compounds expected to
      possess optimized antimicrobial activity. As very little work regarding
      attachment of ether linkages replacing chlorine at C-2 has been reported, it was
      thought worthwhile to synthesize various quinoxaline derivatives by replacing the
      C2 chlorine with an ether linkage attached to a benzene ring possessing an
      aldehyde or a free amino group which can be further reacted with aromatic amines
      and aromatic aldehydes, respectively, to yield new Schiff bases containing
      quinoxaline moieties. Thus the compounds 4-(2-methylquinoxalinyloxy) benzaldehyde
      (4), 2-[4-(substituted-benziminomethyl)-phenoxy]-3-methyl quinoxalines 5a-e, 4-(2
      methyl-quinoxaline-3-yloxy)benzamine (6) and 4-(2-methylquinoxalin-3-yloxy)-N
      substituted benzylidine benzamines 7a-e were synthesized and tested for their
      antimicrobial activity. The structures of the compounds were confirmed on the
      basis of their elemental and spectral data.

PMID- 27713360
TI  - Combinations of drugs in the Treatment of Obesity.
AB  - Obesity is a chronic disease associated with excess morbidity and mortality.
      Clinical treatment, however, currently offers disappointing results, with very
      high rates of weight loss failure or weight regain cycles, and only two drugs
      (orlistat and sibutramine) approved for long-term use. Drugs combinations can be
      an option for its treatment but, although widely used in clinical practice, very
      few data are available in literature for its validation. Our review focuses on
      the rationale for their use, with advantages and disadvantages; on combinations
      often used, with or without studies; and on new perspectives of combinations
      being studied mainly by the pharmaceutical industry.

PMID- 27713362
TI  - The Impact of Residual Symptoms in Major Depression.
AB  - The current definition of remission from major depressive disorder does not fully
      take into account all aspects of patient recovery. Residual symptoms of
      depression are very common in patients who are classified as being in remission.
      Patients with residual symptoms are at increased risk of functional and
      interpersonal impairments, and are at high risk for recurrence of depression.
      This article discusses the incidence of residual symptoms of depression, as well
      as the risks and consequences of these symptoms, and will review the state of
      current treatment.

PMID- 27713363
TI  - Use of Generics-A Critical Cost Containment Measure for All Healthcare
      Professionals in Europe?
AB  - Pharmaceutical expenditures in ambulatory care rose rapidly in Europe in the
      1990s and early 2000s. This was typically faster than other components of
      healthcare spending, leading to reforms to moderate future growth. A number of
      these centered on generic medicines with measures to lower reimbursed prices as
      well as enhance their prescribing and dispensing. The principal objective of this
      paper is to review additional measures that some European countries can adopt to
      further reduce reimbursed prices for generics. Secondly, potential approaches to
      address concerns with generics when they arise to maximize savings. Measures to
      enhance the prescribing of generics will also briefly be discussed. A narrative
      review of the extensive number of publications and associated references from the
      co-authors was conducted supplemented with known internal or web-based articles.
      In addition, health authority and health insurance databases, principally from
      2001 to 2007, were analyzed to assess the impact of the various measures on price
      reductions for generic omeprazole and generic simvastatin vs. pre-patent loss
      prices, as well as overall efficiency in Proton Pump Inhibitor (PPI) and statin
      prescribing. The various initiatives generally resulted in considerable lowering
      of the prices of generics as well as specifically for generic omeprazole and
      generic simvastatin vs. pre-patent loss prices. At one stage in the UK, generic
      simvastatin was just 2% of the originator price. These measures also led to
      increased efficiency for PPI and statin prescribing with reimbursed expenditure
      for the PPIs and statins either falling or increasing at appreciably lower rates
      than increases in utilization. A number of strategies have also been introduced
      to address patient and physician concerns with generics to maximize savings. In
      conclusion, whilst recent reforms have been successful, European countries must
      continue learning from each other to fund increased volumes and new innovative
      drugs as resource pressures grow. Policies regarding generics and their
      subsequent impact on reimbursement and utilization of single sourced products
      will continue to play a key role to release valuable resources. However, there
      must continue to be strategies to address concerns with generics when they exist.

PMID- 27713364
TI  - Non-Steroidal Anti-Inflammatory Drugs in the Carcinogenesis of the
      Gastrointestinal Tract.
AB  - It is estimated that underlying infections and inflammatory responses are linked
      to 15-20% of all deaths from cancer worldwide. Inflammation is a physiologic
      process in response to tissue damage resulting from microbial pathogen infection,
      chemical irritation, and/or wounding. Tissues injured throughout the recruitment
      of inflammatory cells such as macrophages and neutrophils, generate a great
      amount of growth factors, cytokines, and reactive oxygen and nitrogen species
      that may cause DNA damage that in turn predisposes to the transformation from
      chronic inflammation to neoplasia. Cyclooxygenase (COX), playing a key role in
      cell homeostasis, angiogenesis and tumourigenesis, may represent the link between
      inflammation and cancer. Currently COX is becoming a pharmacological target for
      cancer prevention and treatment.It is estimated that underlying infections and
      inflammatory responses are linked to 15-20% of all deaths from cancer worldwide.
      Inflammation is a physiologic process in response to tissue damage resulting from
      microbial pathogen infection, chemical irritation, and/or wounding. Tissues
      injured throughout the recruitment of inflammatory cells such as macrophages and
      neutrophils, generate a great amount of growth factors, cytokines, and reactive
      oxygen and nitrogen species that may cause DNA damage that in turn predisposes to
      the transformation from chronic inflammation to neoplasia. Cyclooxygenase (COX),
      playing a key role in cell homeostasis, angiogenesis and tumourigenesis, may
      represent the link between inflammation and cancer. Currently COX is becoming a
      pharmacological target for cancer prevention and treatment.

PMID- 27713366
TI  - Exenatide Use in the Management of Type 2 Diabetes Mellitus.
AB  - Exenatide is a GLP-1 (glucagon-like peptide-1) agonist that has been approved in
      the UK for use in the management of Type 2 Diabetes Mellitus (T2DM) since 2006.
      It acts by increasing glucose-induced insulin release and by reducing glucagon
      secretion postprandially. It therefore increases insulin secretion and reduces
      glucose levels, especially postprandially. It also reduces gastric emptying and
      acts centrally to promote satiety. In clinical practice it reduces HbA1c (range; 
      0.4% to -1.3%), fasting and postprandial blood glucose levels and is the only
      antidiabetic agent (together with liraglutide; a human GLP-1 analogue) to promote
      weight loss (range; -1.5 kg to -5.5 kg). It can be used as monotherapy or in
      combination with metformin and/or sulphonylureas (SU) and/or thiazolinediones
      (TZD). When compared with insulin it causes similar reductions in HbA1c and
      glucose levels, but unlike insulin it has the advantage of inducing weight loss.
      Its main side effect is gastrointestinal (GI) disturbances; nausea is the
      commonest GI adverse effect, albeit usually mild and transient. Hypoglycaemia is
      uncommon, especially when used as monotherapy or in combination with metformin.
      In this review article we scrutinize the currently available evidence for use of
      exenatide in the management of T2DM.

PMID- 27713367
TI  - Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in
      the Neonate: A Review.
AB  - Bacterial infections are common in the neonates and are a major cause of
      morbidity and mortality. Sixty percent of preterm infants admitted to neonatal
      intensive care units received at least one antibiotic during the first week of
      life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%,
      respectively. Kinetic parameters such as the half-life (t1/2), clearance (Cl),
      and volume of distribution (Vd) change with development, so the kinetics of
      penicillins, cephalosporins and aminoglycosides need to be studied in order to
      optimise therapy with these drugs. The aim of this study is to review the
      pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the
      neonate in a single article in order to provide a critical analysis of the
      literature and thus provide a useful tool in the hands of physicians. The
      bibliographic search was performed electronically using PubMed, as the search
      engine, until February 2nd, 2010. Medline search terms were as follows:
      pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides) AND
      infant, newborn, limiting to humans. Penicillins, cephalosporins and
      aminoglycosides are fairly water soluble and are mainly eliminated by the
      kidneys. The maturation of the kidneys governs the pharmacokinetics of
      penicillins, cephalosporins and aminoglycosides in the neonate. The renal
      excretory function is reduced in preterms compared to term infants and Cl of
      these drugs is reduced in premature infants. Gestational and postnatal ages are
      important factors in the maturation of the neonate and, as these ages proceed, Cl
      of penicillins, cephalosporins and aminoglycosides increases. Cl and t1/2 are
      influenced by development and this must be taken into consideration when planning
      a dosage regimen with these drugs. More pharmacokinetic studies are required to
      ensure that the dose recommended for the treatment of sepsis in the neonate is
      evidence based.

PMID- 27713365
TI  - Brain CB2 Receptors: Implications for Neuropsychiatric Disorders.
AB  - Although previously thought of as the peripheral cannabinoid receptor, it is now
      accepted that the CB2 receptor is expressed in the central nervous system on
      microglia, astrocytes and subpopulations of neurons. Expression of the CB2
      receptor in the brain is significantly lower than that of the CB1 receptor.
      Conflicting findings have been reported on the neurological effects of
      pharmacological agents targeting the CB2 receptor under normal conditions. Under
      inflammatory conditions, CB2 receptor expression in the brain is enhanced and CB2
      receptor agonists exhibit potent anti-inflammatory effects. These findings have
      prompted research into the CB2 receptor as a possible target for the treatment of
      neuroinflammatory and neurodegenerative disorders. Neuroinflammatory alterations
      are also associated with neuropsychiatric disorders and polymorphisms in the CB2
      gene have been reported in depression, eating disorders and schizophrenia. This
      review will examine the evidence to date for a role of brain CB2 receptors in
      neuropsychiatric disorders.

PMID- 27713368
TI  - Mechanism of Allosteric Modulation of the Cys-loop Receptors.
AB  - The cys-loop receptor family is a major family of neurotransmitter-operated ion
      channels. They play important roles in fast synaptic transmission, controlling
      neuronal excitability, and brain function. These receptors are allosteric
      proteins, in that binding of a neurotransmitter to its binding site remotely
      controls the channel function. The cys-loop receptors also are subject to
      allosteric modulation by many pharmaceutical agents and endogenous modulators. By
      binding to a site of the receptor distinct from the neurotransmitter binding
      site, allosteric modulators alter the response of the receptors to their
      agonists. The mechanism of allosteric modulation is traditionally believed to be
      that allosteric modulators directly change the binding affinity of receptors for
      their agonists. More recent studies support the notion that these allosteric
      modulators are very weak agonists or antagonists by themselves. They directly
      alter channel gating, and thus change the distribution of the receptor across
      multiple different affinity states, indirectly influencing receptors' sensitivity
      to agonists. There are two major locations of allosteric modulator binding sites.
      One is in subunit interfaces of the amino-terminal domain. The other is in the
      transmembrane domain close to the channel gating machinery. In this review, we
      also give some examples of well characterized allosteric binding pockets.

PMID- 27713369
TI  - The Potential Role of Cannabinoids in Modulating Serotonergic Signaling by Their
      Influence on Tryptophan Metabolism.
AB  - Phytocannabinoids present in Cannabis plants are well known to exert potent anti
      inflammatory and immunomodulatory effects. Previously, we have demonstrated that
      the psychoactive D9-tetrahydrocannabinol (THC) and the non-psychotropic
      cannabidiol (CBD) modulate mitogen-induced Th1-type immune responses in
      peripheral blood mononuclear cells (PBMC). The suppressive effect of both
      cannabinoids on mitogen-induced tryptophan degradation mediated by indoleamine
      2,3-dioxygenase (IDO), suggests an additional mechanism by which antidepressive
      effects of cannabinoids might be linked to the serotonergic system. Here, we will
      review the role of tryptophan metabolism in the course of cell mediated immune
      responses and the relevance of cannabinoids in serotonergic signaling. We
      conclude that in particular the non-psychotropic CBD might be useful for the
      treatment of mood disorders in patients with inflammatory diseases, since this
      cannabinoid seems to be safe and its effects on activation-induced tryptophan
      degradation by CBD were more potent as compared to THC.

PMID- 27713371
TI  - Overview of Histone Deacetylase Inhibitors in Haematological Malignancies.
AB  - Histone deacetylase inhibitors (HDACi) can induce hyperacetylation of both
      histone and non-histone target resulting in epigenetic reprogramming and altered
      activity, stability and localisation of non-histone proteins to ultimately
      mediate diverse biological effects on cancer cells and their microenvironment.
      Clinical trials have demonstrated single agent HDACi to have activity in
      hematological malignancies, in particular T-cell lymphoma and Hodgkin lymphoma.
      Combination strategies with standard therapies based on pre-clinical data are
      being employed with significant success due to their excellent side effect
      profile. Correlative studies will provide valuable information on the sub-groups
      of patients more likely to respond or be resistant to HDACi therapy, while long
      term monitoring for toxicities is also needed.

PMID- 27713370
TI  - The Role of Cannabinoid Receptors in the Descending Modulation of Pain.
AB  - The endogenous antinociceptive descending pathway represents a circuitry of the
      supraspinal central nervous system whose task is to counteract pain. It includes
      the periaqueductal grey (PAG)-rostral ventromedial medulla (RVM)-dorsal horn (DH)
      axis, which is the best characterized pain modulation system through which pain
      is endogenously inhibited. Thus, an alternative rational strategy for silencing
      pain is the activation of this anatomical substrate. Evidence of the involvement
      of cannabinoid receptors (CB) in the supraspinal modulation of pain can be found
      in several studies in which intra-cerebral microinjections of cannabinoid ligands
      or positive modulators have proved to be analgesic in different pain models,
      whereas cannabinoid receptor antagonists or antisense nucleotides towards CB1
      receptors have facilitated pain. Like opioids, cannabinoids produce centrally
      mediated analgesia by activating a descending pathway which includes PAG and its
      projection to downstream RVM neurons, which in turn send inhibitory projections
      to the dorsal horn of the spinal cord. Indeed, several studies underline a
      supraspinal regulation of cannabinoids on g-aminobutyric acid (GABA) and
      glutamate release which inhibit and enhance the antinociceptive descending
      pathway, respectively. Cannabinoid receptor activation expressed on presynaptic
      GABAergic terminals reduces the probability of neurotransmitter release thus dis
      inhibiting the PAG-RVM-dorsal horn antinociceptive pathway. Cannabinoids seem to
      increase glutamate release (maybe as consequence of GABA decrease) and to require
      glutamate receptor activation to induce antinociception. The consequent outcome
      is behavioral analgesia, which is reproduced in several pain conditions, from
      acute to chronic pain models such as inflammatory and neuropathic pain. Taken
      together these findings would suggest that supraspinal cannabinoid receptors have
      broad applications, from pain control to closely related central nervous system
      diseases such as anxiety and depression.

PMID- 27713372
TI  - Cannabinoids and Dementia: A Review of Clinical and Preclinical Data.
AB  - The endocannabinoid system has been shown to be associated with neurodegenerative
      diseases and dementia. We review the preclinical and clinical data on
      cannabinoids and four neurodegenerative diseases: Alzheimer's disease (AD),
      Huntington's disease (HD), Parkinson's disease (PD) and vascular dementia (VD).
      Numerous studies have demonstrated an involvement of the cannabinoid system in
      neurotransmission, neuropathology and neurobiology of dementias. In addition,
      several candidate compounds have demonstrated efficacy in vitro. However, some of
      the substances produced inconclusive results in vivo. Therefore, only few trials
      have aimed to replicate the effects seen in animal studies in patients. Indeed,
      the literature on cannabinoid administration in patients is scarce. While
      preclinical findings suggest causal treatment strategies involving cannabinoids,
      clinical trials have only assessed the suitability of cannabinoid receptor
      agonists, antagonists and cannabidiol for the symptomatic treatment of dementia.
      Further research is needed, including in vivo models of dementia and human
      studies.

PMID- 27713373
TI  - Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic
      Drug Therapy.
AB  - Genetic polymorphisms in the genes that encode drug-metabolizing enzymes are
      implicated in the inter-individual variability in the pharmacokinetics and
      pharmaco-dynamics of antiepileptic drugs (AEDs). However, the clinical impact of
      these polymorphisms on AED therapy still remains controversial. The defective
      alleles of cytochrome P450 (CYP) 2C9 and/or CYP2C19 could affect not only the
      pharmacokinetics, but also the pharmacodynamics of phenytoin therapy. CYP2C19
      deficient genotypes were associated with the higher serum concentration of an
      active metabolite of clobazam, N-desmethylclobazam, and with the higher clinical
      efficacy of clobazam therapy than the other CYP2C19 genotypes. The defective
      alleles of CYP2C9 and/or CYP2C19 were also found to have clinically significant
      effects on the inter-individual variabilities in the population pharmacokinetics
      of phenobarbital, valproic acid and zonisamide. EPHX1 polymorphisms may be
      associated with the pharmacokinetics of carbamazepine and the risk of phenytoin
      induced congenital malformations. Similarly, the UDP-glucuronosyltransferase 2B7
      genotype may affect the pharmacokinetics of lamotrigine. Gluthatione S
      transferase null genotypes are implicated in an increased risk of hepatotoxicity
      caused by carbamazepine and valproic acid. This article summarizes the state of
      research on the effects of mutations of drug-metabolizing enzymes on the
      pharmacokinetics and pharmacodynamics of AED therapies. Future directions for the
      dose-adjustment of AED are discussed.

PMID- 27713375
TI  - Clinical Toxicities of Histone Deacetylase Inhibitors.
AB  - The HDAC inhibitors are a new family of antineoplastic agents. Since the entry of
      these agents into our therapeutic armamentarium, there has been increasing
      interest in their use. Although this family comprises chemical compounds from
      unrelated chemical classes that have different HDAC isoform specificities, they
      surprisingly have very similar toxicity profiles. In contrast, the observed
      toxicity profile is somewhat different from that of traditional cytotoxic
      chemotherapeutic agents and from other epigenetic agents. While some of the side
      effects may be familiar to the oncologist, others are less commonly seen. As some
      patients remain on therapy for a prolonged period of time, the long-term sequelae
      need to be characterized. In addition, since preclinical models suggest promising
      activity when used in combination with other antineoplastic agents, combination
      trials are being pursued. It will thus be important to distinguish the relative
      toxicity attributed to these agents and be alert to the exacerbation of
      toxicities observed in single agent studies. Notably, few of the agents in this
      class have completed phase 2 testing. Consequently, more clinical experience is
      needed to determine the relative frequency of the observed side effects, and to
      identify and develop approaches to mitigate potential clinical sequelae.

PMID- 27713374
TI  - Dendritic Cell Regulation by Cannabinoid-Based Drugs.
AB  - Cannabinoid pharmacology has made important advances in recent years after the
      cannabinoid system was discovered. Studies in experimental models and in humans
      have produced promising results using cannabinoid-based drugs for the treatment
      of obesity and cancer, as well as neuroinflammatory and chronic inflammatory
      diseases. Moreover, as we discuss here, additional studies also indicates that
      these drugs have immunosuppressive and anti-inflammatory properties including
      modulation of immune cell function. Thus, manipulation of the endocannabinoid
      system in vivo may provide novel therapeutic strategies against inflammatory
      disorders. At least two types of cannabinoid receptors, cannabinoid 1 and
      cannabinoid 2 receptors are expressed on immune cells such as dendritic cells
      (DC). Dendritic cells are recognized for their critical role in initiating and
      maintaining immune responses. Therefore, DC are potential targets for cannabinoid
      mediated modulation. Here, we review the effects of cannabinoids on DC and
      provide some perspective concerning the therapeutic potential of cannabinoids for
      the treatment of human diseases involving aberrant inflammatory processes.

PMID- 27713378
TI  - Role of the G Protein-Coupled Receptor, mGlu1, in Melanoma Development.
AB  - Melanoma remains one of the cancers for which a decline in morbidity has not been
      achieved with current scientific and medical advances. Mono-therapies targeting
      melanoma have been largely ineffective, increasing the need for identification of
      new drugable targets. Multiple tumor suppressors and oncogenes that impart
      genetic predisposition to melanoma have been identified and are being studied in
      an attempt to provide insight on the development of anti-melanoma therapies.
      Metabotropic Glutamate Receptor I (GRM1) has recently been implicated as a novel
      oncogene involved in melanomagenesis. GRM1 (mGlu1, protein) belongs to the G
      protein coupled receptor (GPCR) super family and is normally functional in the
      central nervous system. Our group showed in a transgenic mouse model system that
      ectopic expression of Grm1 in melanocytes is sufficient to induce spontaneous
      melanoma development in vivo. GPCRs are some of the most important therapeutic
      drug targets discovered to date and they make up a significant proportion of
      existing therapies. This super family of transmembrane receptors has wide spread
      expression and interacts with a diverse array of ligands. Diverse physiological
      responses can be induced by stimulator(s) or suppressor(s) of GPCRs, which
      contributes to their attractiveness in existing and emerging therapies. GPCR
      targeting therapies are employed against a variety of human disorders including
      those of the central nervous system, cardiovascular, metabolic, urogenital and
      respiratory systems. In the current review, we will discuss how the
      identification of the oncogenic properties of GRM1 opens up new strategies for
      the design of potential novel therapies for the treatment of melanoma.

PMID- 27713376
TI  - Identifying the Ion Channels Responsible for Signaling Gastro-Intestinal Based
      Pain.
AB  - We are normally unaware of the complex signalling events which continuously occur
      within our internal organs. Most of us only become cognisant when sensations of
      hunger, fullness, urgency or gas arise. However, for patients with organic and
      functional bowel disorders pain is an unpleasant and often debilitating reminder.
      Furthermore, chronic pain still represents a large unmet need for clinical
      treatment. Consequently, chronic pain has a considerable economic impact on
      health care systems and the afflicted individuals. In order to address this need
      we must understand how symptoms are generated within the gut, the molecular
      pathways responsible for generating these signals and how this process changes in
      disease states.

PMID- 27713379
TI  - Allosteric Modulation of Muscarinic Acetylcholine Receptors.
AB  - An allosteric modulator is a ligand that binds to an allosteric site on the
      receptor and changes receptor conformation to produce increase (positive
      cooperativity) or decrease (negative cooperativity) in the binding or action of
      an orthosteric agonist (e.g., acetylcholine). Since the identification of
      gallamine as the first allosteric modulator of muscarinic receptors in 1976, this
      unique mode of receptor modulation has been intensively studied by many groups.
      This review summarizes over 30 years of research on the molecular mechanisms of
      allosteric interactions of drugs with the receptor and for new allosteric
      modulators of muscarinic receptors with potential therapeutic use. Identification
      of positive modulators of acetylcholine binding and function that enhance
      neurotransmission and the discovery of highly selective allosteric modulators are
      mile-stones on the way to novel therapeutic agents for the treatment of
      schizophrenia, Alzheimer's disease and other disorders involving impaired
      cognitive function.

PMID- 27713381
TI  - Antiepileptic Drug Discovery and Development: What Have We Learned and Where Are
      We Going?
AB  - Current marketed antiepileptic drugs (AEDs) consist of a variety of structural
      classes with different mechanisms of action. These agents typically have non
      overlapping efficacy and side-effect profiles presenting multiple treatment
      options for the patient population. However, approximately 30% of seizure
      sufferers fail to respond to current therapies often because poorly tolerated
      side-effects limit adequate dosing. The scope of this review is to summarize
      selected advances in 2nd and 3rd generation AEDs as well as compounds in
      development with novel mechanisms of action.

PMID- 27713377
TI  - Vulnerability Factors for the Psychiatric and Behavioral Effects of Cannabis.
AB  - Cogent evidence shows that cannabis plays a variable role on behavioral
      regulation and the pathophysiology of most psychiatric conditions. Accordingly,
      cannabis has been alternatively shown to exacerbate or ameliorate mental
      symptoms, depending on its composition and route of consumption, as well as
      specific individual and contextual characteristics. The vulnerability to the
      psychological effects of cannabis is influenced by a complex constellation of
      genetic and environmental factors. In the present article, we will review the
      current evidence on the pharmacological, individual and situational factors that
      have been documented to affect the behavioral and psychiatric effects of
      cannabinoids.

PMID- 27713380
TI  - Antidepressants and Suicide Risk: A Comprehensive Overview.
AB  - The annual worldwide suicide rate currently averages approximately 13 per 100,000
      individuals per year (0.013% per year), with higher average rates for men than
      for women in all but a few countries, very low rates in children, and relatively
      high rates in elderly men. Suicide rates vary markedly between countries,
      reflecting in part differences in case-identification and reporting procedures.
      Rates of attempted suicide in the general population average 20-30 times higher
      than rates of completed suicide, but are probably under-reported. Research on the
      relationship between pharmacotherapy and suicidal behavior was rare until a
      decade ago. Most ecological studies and large clinical studies have found that a
      general reduction in suicide rates is significantly correlated with higher rates
      of prescribing modern antidepressants. However, ecological, cohort and case
      control studies and data from brief, randomized, controlled trials in patients
      with acute affective disorders have found increases, particularly in young
      patients and particularly for the risk of suicide attempts, as well as increases
      in suicidal ideation in young patients. whether antidepressants are associated
      with specific aspects of suicidality (e.g., higher rates of completed suicide,
      attempted suicide and suicidal ideation) in younger patients with major affective
      disorders remains a highly controversial question. In light of this gap this
      paper analyzes research on the relationship between suicidality and
      antidepressant treatment.

PMID- 27713382
TI  - Antifungal Properties of Chenopodium ambrosioides Essential Oil Against Candida
      Species.
AB  - The essential oil of the aerial part (leaves, flowers and stem) of Chenopodium
      ambrosioides was obtained by hydrodistillation and its chemical composition
      analyzed by GC and GC/MS, which permitted the identification of 14 components,
      representing 98.8% of the total oil. Major components were alpha-terpinene
      (51.3%), p-cymene (23.4%) and p-mentha-1,8-diene (15.3%). The antifungal
      properties of this essential oil were investigated in vitro by the well diffusion
      and broth microdilution methods. The in vitro antifungal activity was
      concentration dependent and minimum inhibitory concentration values varied from
      0.25 to 2 mg/mL. The in vivo antifungal activity was evaluated on an induced
      vaginal candidiasis rat model. The in vivo activity of the oil on mice vaginal
      candidiasis was not dose-dependent. Indeed, all the three tested doses; 0.1%, 1%
      and 10% led to the recovery of mice from the induced infection after 12 days of
      treatment. The effect of the essential oil on C. albicans ATCC 1663 fatty acid
      profile was studied. This oil has a relatively important dose-dependent effect on
      the fatty acids profile.

PMID- 27713385
TI  - The Art of Managing Conversions between Antiepileptic Drugs: Maximizing Patient
      Tolerability and Quality of Life.
AB  - Conversion between anti-epilectic drugs (AEDs) is frequently necessary in
      epilepsy care, exposing patients to a risk of incurring adverse effects and
      reduced quality of life. Little practical guidance is available to practitioners
      to guide conversions between AED monotherapies, or in adding a new adjunctive AED
      into a polytherapy regimen. This article reviews the impact of adverse effects of
      AEDs on quality of life in epilepsy patients, then reviews several important
      patient-related factors such as age, gender, medical and psychiatric co
      morbidities, and co-medications that must be considered when selecting AEDs and
      ensuring tolerable and safe AED conversions. Practical strategies for
      transitional polytherapy AED conversion are then considered in different commonly
      encountered clinical scenarios in newly diagnosed and refractory epilepsy care,
      including inadequate seizure control, intolerable adverse effects, or
      idiosyncratic safety hazards. Successful conversion between AEDs requires regular
      monitoring for patient-reported adverse effects and appropriately reactive
      adjustment of AED therapy to maximize patient quality of life.

PMID- 27713384
TI  - Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against
      Chemotherapy-Induced Acute and Delayed Vomiting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is a complex pathophysiological
      condition and consists of two phases. The conventional CINV neurotransmitter
      hypothesis suggests that the immediate phase is mainly due to release of
      serotonin (5-HT) from the enterochromaffin cells in the gastrointestinal tract
      (GIT), while the delayed phase is a consequence of release of substance P (SP) in
      the brainstem. However, more recent findings argue against this simplistic
      neurotransmitter and anatomical view of CINV. Revision of the hypothesis
      advocates a more complex, differential and overlapping involvement of several
      emetic neurotransmitters/modulators (e.g. dopamine, serotonin, substance P,
      prostaglandins and related arachidonic acid derived metabolites) in both phases
      of emesis occurring concomitantly in the brainstem and in the GIT enteric nervous
      system (ENS) [1]. No single antiemetic is currently available to completely
      prevent both phases of CINV. The standard antiemetic regimens include a 5-HT3
      antagonist plus dexamethasone for the prevention of acute emetic phase, combined
      with an NK1 receptor antagonist (e.g. aprepitant) for the delayed phase. Although
      NK1 antagonists behave in animals as broad-spectrum antiemetics against different
      emetogens including cisplatin-induced acute and delayed vomiting, by themselves
      they are not very effective against CINV in cancer patients. Cannabinoids such as
      D8-THC also behave as broad-spectrum antiemetics against diverse emetic stimuli
      as well as being effective against both phases of CINV in animals and patients.
      Potential side effects may limit the clinical utility of direct-acting
      cannabinoid agonists which could be avoided by the use of corresponding indirect
      acting agonists. Cannabinoids (both phyto-derived and synthetic) behave as
      agonist antiemetics via the activation of cannabinoid CB1 receptors in both the
      brainstem and the ENS emetic loci. An endocannabinoid antiemetic tone may exist
      since inverse CB1 agonists (but not the corresponding silent antagonists) cause
      nausea and vomiting.

PMID- 27713383
TI  - From Fertilisation to Implantation in Mammalian Pregnancy-Modulation of Early
      Human Reproduction by the Endocannabinoid System.
AB  - There is an increasing recognition that the endocannabinoid system is the crucial
      cytokine-hormone system regulating early human pregnancy. The synchronous
      development of the fertilized embryo and the endometrium to ensure timely
      implantation has been shown to be one of the pivotal steps to successful
      implantation. This development is thought to be regulated by a finely balanced
      relationship between various components of the endocannabinoid system in the
      endometrium, the embryo and the Fallopian tube. In addition, this system has also
      been shown to be involved in the regulation of the development and maturation of
      the gametes prior to fertilization. In this review, we will examine the evidence
      from animal and human studies to support the role of the endocannabinoid system
      in gametogenesis, fertilization, implantation, early pregnancy maintenance, and
      in immunomodulation of pregnancy. We will discuss the role of the cannabinoid
      receptors and the enzymes involved in the synthesis and degradation of the key
      endocannabinoid ligands (e.g., anandamide and 2-arachinoylglycerol) in early
      reproduction.

PMID- 27713386
TI  - Tissue Engineering of Cartilage; Can Cannabinoids Help?
AB  - This review discusses the role of the cannabinoid system in cartilage tissue and
      endeavors to establish if targeting the cannabinoid system has potential in
      mesenchymal stem cell based tissue-engineered cartilage repair strategies. The
      review discusses the potential of cannabinoids to protect against the degradation
      of cartilage in inflamed arthritic joints and the influence of cannabinoids on
      the chondrocyte precursors, mesenchymal stem cells (MSCs). We provide
      experimental evidence to show that activation of the cannabinoid system enhances
      the survival, migration and chondrogenic differentiation of MSCs, which are three
      major tenets behind the success of a cell-based tissue-engineered cartilage
      repair strategy. These findings highlight the potential for cannabinoids to
      provide a dual function by acting as anti-inflammatory agents as well as
      regulators of MSC biology in order to enhance tissue engineering strategies aimed
      at cartilage repair.

PMID- 27713387
TI  - The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression
      and Mood Disorders.
AB  - Aggressive symptomatology presents across multiple psychiatric, developmental,
      neurological and behavioral disorders, complicating the diagnosis and treatment
      of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing
      alternative in the treatment of aggression, mood lability and impulsivity in
      adult and pediatric populations, although few controlled trials have explored
      their efficacy in treating pediatric populations. This review of the literature
      synthesizes the available data on ten AEDs - valproate, carbamazepine,
      oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide,
      gabapentin and tiagabine - in an attempt to assess evidence for the efficacy of
      AEDs in the treatment of aggression in pediatric populations. Our review revealed
      modest evidence that some of the AEDs produced improvement in pediatric
      aggression, but controlled trials in pediatric bipolar disorder have not been
      promising. Valproate is the best supported AED for aggression and should be
      considered as a first line of treatment. When monotherapy is insufficient,
      combining an AED with either lithium or an atypical anti-psychotic can result in
      better efficacy. Additionally, our review indicates that medications with
      predominately GABA-ergic mechanisms of action are not effective in treating
      aggression, and medications which decrease glutaminergic transmission tended to
      have more cognitive adverse effects. Agents with multiple mechanisms of action
      may be more effective.

PMID- 27713388
TI  - Oral Hypoglycemic Drugs: Pathophysiological Basis of Their Mechanism of
      ActionOral Hypoglycemic Drugs: Pathophysiological Basis of Their Mechanism of
      Action.
AB  - Type 2 diabetes is a syndrome characterized by relative insulin deficiency,
      insulin resistance and increased hepatic glucose output. Medications used to
      treat the disease are designed to correct one or more of these metabolic
      abnormalities. Current recommendations of the American Diabetes Association (ADA)
      and European Association for the Study of Diabetes (EASD) include diet and
      exercise as first-line therapy plus hypoglycemic drugs. Actually there are seven
      distinct classes of anti-hyperglicemic agents, each of them displaying unique
      pharmacologic properties. The aim of this review is to describe the
      pathophysiological basis of their mechanism of action, a necessary step to
      individualize treatment of diabetic people, taking into proper consideration
      potential benefits and secondary effects of drugs.

PMID- 27713390
TI  - Association of STin2 VNTR Polymorphism of Serotonin Transporter Gene with
      Lifelong Premature Ejaculation: A Case-Control Study in Han Chinese Subjects.
AB  - BACKGROUND The STin2 VNTR polymorphism has a variable number of tandem repeats in
      intron 2 of the serotonin transporter gene. We aimed to explore the relationship
      between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE).
      MATERIAL AND METHODS We recruited a total of 115 outpatients who complained of
      ejaculating prematurely and who were diagnosed as LPE, and 101 controls without
      PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based
      technology. We evaluated the associations between STin2 VNTR allelic and
      genotypic frequencies and LPE, as well as the intravaginal ejaculation latency
      time (IELT) of different STin2 VNTR genotypes among LPE patients. RESULTS The
      patients and controls did not differ significantly in terms of any characteristic
      except age. A significantly higher frequency of STin2.12/12 genotype was found
      among LPE patients versus controls (P=0.026). Frequency of patients carrying at
      least 1 copy of the 10-repeat allele was significantly lower compared to the
      control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31-0.97, P=0.040). In the LPE
      group, the mean IELT showed significant difference in STin2.12/12 genotype when
      compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10
      repeat allele carriers was 50% longer compared to homozygous carriers of the
      STin2.12 allele. CONCLUSIONS Our results indicate the presence of STin2.10 allele
      is a protective factor for LPE. Men carrying the higher expression genotype
      STin2. 12/12 have shorter IELT than 10-repeat allele carriers.

PMID- 27713389
TI  - Diagnosis and Treatment of Small Bowel Strangulation Due To Congenital Band:
      Three Cases of Congenital Band in Adults Lacking a History of Trauma or Surgery.
AB  - BACKGROUND Among the causes of constipation are bands and adhesions that lead to
      obstructions at different points in the intestinal tract. These can occur as a
      consequence of healing following surgery or trauma. However, an entity known as
      congenital band exists where a band is present from birth. Here we report three
      such cases of adults with symptoms of intestinal obstruction, in whom a
      congenital band was discovered through exploratory laparoscopy. CASE REPORT All
      three of these patients presented lacking a history of any abdominal trauma or
      previous abdominal surgeries, a fact that is often used to exclude an adhesion as
      a differential. All three recovered quickly and had relief of their symptoms
      following surgical intervention. CONCLUSIONS Bands and adhesions are common
      surgical causes of small bowel obstruction, leading to symptoms such as nausea,
      vomiting, constipation, and obstipation. These bands almost always result from a
      prior abdominal surgery or from a recent abdominal trauma. The three cases
      presented here show a far more unusual picture of a band, one that is
      congenitally present, as there was an absence of such a history. This is
      significant because clinical suspicion of a band is often very low due to a lack
      of distinguishing clinical and diagnostic features, and when the past history is
      negative.

PMID- 27713391
TI  - Resolution of Hepatic Venous Congestion Following Gradual Occlusion of Middle
      Hepatic Vein Interposition Graft in Living Donor Liver Transplantation.
AB  - BACKGROUND The middle hepatic vein (MHV) interposition vessel graft (IVG) is
      often occluded within a few months after living-donor liver transplantation
      (LDLT). We aimed to assess the mechanisms of resolving the hepatic venous
      congestion (HVC) that develops after gradual occlusion of the MHV-IVG. MATERIAL
      AND METHODS This study comprised two parts. Part I involved an assessment of the
      process of HVC resolution in the remnant right liver after donation of an
      extended left liver graft (n=100). Part II involved an evaluation of the timing
      and patterns of gradual MHV-IVG occlusion and HVC resolution in LDLT recipients
      (n=100). RESULTS In Part I, the analysis of 1-week dynamic computed tomography
      (CT) showed pre-existing collaterals in 8, appropriate compensation in 44, and
      HVC in 48 patients. In Part II, reconstruction of a segment V vein (V5) and a
      segment VIII vein (V8) was the most common reconstruction type (n=65). The
      patency rates of MHV-IVG were 90% at 3 months, 65% at 6 months, 37% at 12 months,
      and 18% at 24 months. The patency rate of V5 was inferior to that of V8. CT
      imaging analysis indicated that extrinsic compression of IVG, development of
      intrahepatic collaterals, and IVG shrinkage were the main mechanisms underlying
      late MHV-IVG occlusion. Moreover, the timing of MHV-IVG occlusion was well
      correlated with that of neo-collateralization. CONCLUSIONS MHV-IVG reconstruction
      effectively prevents HVC in LDLT. Although gradual MHV-IVG occlusion is well
      compensated by neo-collateralization, we believe that the patency of the IVG
      should be maintained for at least 6 months after LDLT.

PMID- 27713392
TI  - [Linee guida flebo-linfologiche SIF-SICVE 2016 della Societa Italiana di
      Flebologia e della Societa Italiana di Chirurgia Vascolare ed Endovascolare].
AB  - Phlebology is not a specialty for its own in Italy. Phlebological patients are
      treated by vascular and general surgeons, dermatologists, phlebologists,
      angiologists, internists and even general practitioners. Even tough guidelines
      present a series of recommendations based on evidence-based medicine, guidelines
      may also be a tool to unify the diagnostic and therapeutic approach in a vast
      medical field like phlebology. Since vascular surgeons and phlebologists are
      particularly involved in phlebology-related pathologies the scientific societies
      of the Italian Society of Phlebology (SIF) and the Italian Society for Vascular
      and Endovascular Surgery (SICVE) decided to cooperate for the preparation of
      phlebo-lymphological guidelines. These guidelines comprehend also an important
      chapter dealing with the lymphology of the lower extremities; phlebological
      active physicians are often faced with lymphatic pathologies and a good
      differential diagnosis can be sometimes very helpful. Sclerotherapy and Surgery
      as the major therapeutical alternatives are extensively analyzed, but also the
      compression therapy, the medical and physical therapy are presented under the
      critical view of evidence based analyses. Separate chapters deal with the
      treatment alternatives for superficial and deep venous thromboses and the
      recommendations for the treatment of venous ulcers. The current scientific
      evidences were confronted with the experiences of Italian specialists and the
      particular practice and reality in Italy. They represent therefore the actual
      valid positions and recommendations in Italy which shall be updated regularly.

PMID- 27713393
TI  - Impact of inhibitor of apoptosis proteins on immune modulation and inflammation.
AB  - The routes leading to programmed cell death are as tightly regulated as those of
      cellular growth and proliferation, and a finely synchronized balance between the
      life and death of cells ensures proper organ size and function. Inhibitors of
      apoptosis (IAPs) proteins were initially characterized by their ability to
      directly bind and inhibit apoptotic caspases. However, recent studies have
      clarified that IAPs are much more functionally versatile, modulating a vast range
      of signaling pathways that have an impact on antimicrobial responses,
      tumorigenesis, metastasis and cellular migration. A significant contribution of
      IAPs in tumorigenesis is their inherent function as E3 ubiquitin ligases to
      modulate cellular signaling downstream of death receptors or certain pattern
      recognition receptors. In this review, we focus on modulation of the innate and
      adaptive immune systems, macrophage plasticity and inflammatory responses by IAP
      family members. We also explore the rationale to target IAPs pharmacologically
      for the treatment of a number of inflammatory diseases and cancer.

PMID- 27713394
TI  - Effect of growth hormone and IgG aggregates on dendritic cells activation and T
      cells polarization.
AB  - Patients treated with therapeutic biological products (BP) frequently develop
      anti-drug antibodies (ADA) with potential neutralizing capacities leading to loss
      of clinical response or serious side effects. BP aggregates have been suggested
      to promote immunogenicity, thus enhancing ADA production. Dendritic cells (DC)
      are key effectors in T-cell and B-cell fates, and the subsequent generation of
      immunogenicity. The objective of this work was to determine if BP aggregates can
      participate to DC maturation and T-cell activation. We compared aggregates from
      three different proteins: human growth hormone (hGH), Rituximab, a chimeric anti
      CD20 antibody and a serum-purified human IgG1. All three proteins underwent a
      stir stress, generating comparable populations of aggregated particles.
      Maturation of human monocyte-derived DC (moDC) upon exposure to native BPs or
      aggregates was evaluated in vitro. Results showed that hGH aggregates induced an
      increased expression of moDC co-stimulation markers, and augmented levels of IL
      6, IL-8, IL-12p40, CCL2, CCL3, CCL4 and CXCL10. Both antibodies aggregates were
      also able to modify DC phenotype, but cytokine and chemokine productions were
      seen only with IL-6, IL-8, IL-12p40 and CXCL10. Aggregates-treated moDC enhanced
      allogenic T-cell proliferation and cytokines production, suggesting Th1
      polarization with hGH, and mixed T-cell responses with antibodies aggregates.
      These results showed that BP aggregates provoked DC maturation, thus driving
      adaptive T-cell responses and polarization.

PMID- 27713395
TI  - An interdigit signalling centre instructs coordinate phalanx-joint formation
      governed by 5'Hoxd-Gli3 antagonism.
AB  - The number of phalanges and joints are key features of digit 'identity' and are
      central to limb functionality and evolutionary adaptation. Prior chick work
      indicated that digit phalanges and their associated joints arise in a different
      manner than the more sparsely jointed long bones, and their identity is regulated
      by differential signalling from adjacent interdigits. Currently, there is no
      genetic evidence for this model, and the molecular mechanisms governing digit
      joint specification remain poorly understood. Using genetic approaches in mouse,
      here we show that functional 5'Hoxd-Gli3 antagonism acts indirectly, through Bmp
      signalling from the interdigital mesenchyme, to regulate specification of joint
      progenitors, which arise in conjunction with phalangeal precursors at the digit
      tip. Phalanx number, although co-regulated, can be uncoupled from joint
      specification. We propose that 5'Hoxd genes and Gli3 are part of an interdigital
      signalling centre that sets net Bmp signalling levels from different interdigits
      to coordinately regulate phalanx and joint formation.

PMID- 27713396
TI  - Motor cortex activity predicts response alternation during sensorimotor
      decisions.
AB  - Our actions are constantly guided by decisions based on sensory information. The
      motor cortex is traditionally viewed as the final output stage in this process,
      merely executing motor responses based on these decisions. However, it is not
      clear if, beyond this role, the motor cortex itself impacts response selection.
      Here, we report activity fluctuations over motor cortex measured using MEG, which
      are unrelated to choice content and predict responses to a visuomotor task
      seconds before decisions are made. These fluctuations are strongly influenced by
      the previous trial's response and predict a tendency to switch between response
      alternatives for consecutive decisions. This alternation behaviour depends on the
      size of neural signals still present from the previous response. Our results
      uncover a response-alternation bias in sensorimotor decision making. Furthermore,
      they suggest that motor cortex is more than an output stage and instead shapes
      response selection during sensorimotor decision making.

PMID- 27713397
TI  - Experimental creation of quantum Zeno subspaces by repeated multi-spin
      projections in diamond.
AB  - Repeated observations inhibit the coherent evolution of quantum states through
      the quantum Zeno effect. In multi-qubit systems this effect provides
      opportunities to control complex quantum states. Here, we experimentally
      demonstrate that repeatedly projecting joint observables of multiple spins
      creates quantum Zeno subspaces and simultaneously suppresses the dephasing caused
      by a quasi-static environment. We encode up to two logical qubits in these
      subspaces and show that the enhancement of the dephasing time with increasing
      number of projections follows a scaling law that is independent of the number of
      spins involved. These results provide experimental insight into the interplay
      between frequent multi-spin measurements and slowly varying noise and pave the
      way for tailoring the dynamics of multi-qubit systems through repeated
      projections.

PMID- 27713398
TI  - Mechanisms of aging-related proteinopathies in Caenorhabditis elegans.
AB  - Aging is the most important risk factor for human neurodegenerative diseases such
      as Alzheimer's and Parkinson's diseases. Pathologically, these diseases are
      characterized by the deposition of specific protein aggregates in neurons and
      glia, representing the impairment of neuronal proteostasis. However, the
      mechanism by which aging affects the proteostasis system and promotes protein
      aggregation remains largely unknown. The short lifespan and ample genetic
      resources of Caenorhabditis elegans (C. elegans) have made this species a
      favorite model organism for aging research, and the development of proteinopathy
      models in this organism has helped us to understand how aging processes affect
      protein aggregation and neurodegeneration. Here, we review the recent literature
      on proteinopathies in C. elegans models and discuss the insights we have gained
      into the mechanisms of how aging processes are integrated into the pathogenesis
      of various neurodegenerative diseases.

PMID- 27713399
TI  - A novel anti-IL4Ralpha nanoparticle efficiently controls lung inflammation during
      asthma.
AB  - Drug resistance and the harmful side effects accompanying the prolonged
      corticosteroid treatment of chronic pulmonary diseases prompted the development
      of more specific anti-inflammatory approaches. Several strategies aiming to block
      IL4Ralpha, the receptor for a key pro-inflammatory pathway, were investigated.
      However, their efficiency was limited, mostly due to the systemic or subcutaneous
      route of administrations. In this paper, we examined the ability of an intranasal
      treatment with biocompatible nanoparticles targeting IL4Ralpha to control lung
      inflammation in ovalbumin (OVA)-sensitized mice. OVA-sensitized mice were treated
      with anti-IL4Ralpha-conjugated nanoparticles. The levels of pro-inflammatory
      cytokines in the lungs and broncho-alveolar lavage fluid (BALF) were determined
      using a cytokine array assay. The effects of nanoparticle treatment on the
      activation of lung inflammatory cells and their ability to proliferate and
      produce cytokines were determined using fluorescence-activated cell sorting
      (FACS) analysis. Lung inflammation was also monitored using immunohistochemical
      staining. Treatment with the anti-IL4Ralpha nanoparticles significantly decreased
      pro-inflammatory cytokine expression and release in BALF and airway lung tissue
      in mice. The numbers of lung tissue lymphocytes, neutrophils and eosinophils were
      also decreased. Interestingly, anti-IL4Ralpha nanoparticles deactivated CD4 and
      CD8 T cells in lung tissue and inhibited their ability to produce pro
      inflammatory cytokines to a significantly lower level than the treatment with
      free anti-IL4Ralpha. Moreover, they induced a sustained low level of lung
      inflammation for 1 week following the last instillation compared with the
      treatment with free anti-IL4Ralpha antibodies. Together, this data suggested that
      the enhanced tissue penetrability and sustainability of these nanoparticles
      improved the strength and durability of the immunosuppressive effects of anti
      IL4Ralpha.

PMID- 27713400
TI  - Non-enzymatic pyridine ring formation in the biosynthesis of the rubrolone
      tropolone alkaloids.
AB  - The pyridine ring is a potent pharmacophore in alkaloid natural products.
      Nonetheless, its biosynthetic pathways are poorly understood. Rubrolones A and B
      are tropolone alkaloid natural products possessing a unique tetra-substituted
      pyridine moiety. Here, we report the gene cluster and propose a biosynthetic
      pathway for rubrolones, identifying a key intermediate that accumulates upon
      inactivation of sugar biosynthetic genes. Critically, this intermediate was
      converted to the aglycones of rubrolones by non-enzymatic condensation and
      cyclization with either ammonia or anthranilic acid to generate the respective
      pyridine rings. We propose that this non-enzymatic reaction occurs via hydrolysis
      of the key intermediate, which possesses a 1,5-dione moiety as an amine acceptor
      capable of cyclization. This study suggests that 1,5-dione moieties may represent
      a general strategy for pyridine ring biosynthesis, and more broadly highlights
      the utility of non-enzymatic diversification for exploring and expanding natural
      product chemical space.

PMID- 27713401
TI  - Synergism between RIZ1 gene therapy and paclitaxel in SiHa cervical cancer cells.
AB  - RIZ1 is a tumor suppressor gene. The purpose of the present study was to
      investigate the inhibitory effect of RIZ1 gene therapy on the growth of SiHa
      cervical cancer cells and its synergism with paclitaxel. The expression levels of
      RIZ1 were examined by real-time PCR and western blotting before and after
      transfection of RIZ1. The effects of paclitaxel or pcDNA3.1(+)-RIZ1 alone or in
      combination, on the proliferation of SiHa cells were evaluated by MTT method. The
      inhibitory effect on the proliferation of SiHa cells was more significant in the
      pcDNA3.1(+)-RIZ1 combined with paclitaxel group than in the pcDNA3.1(+)-RIZ1 or
      paclitaxel groups (P<0.05). The expression level of RIZ1 in SiHa cells increased
      after treatment with paclitaxel, which indicated a synergism between them. RIZ1
      gene therapy combined with paclitaxel showed stronger cell inhibition than
      paclitaxel alone, which indicated a synergism between them.

PMID- 27713402
TI  - Structural characterization of antibiotic self-immunity tRNA synthetase in plant
      tumour biocontrol agent.
AB  - Antibiotic-producing microbes evolved self-resistance mechanisms to avoid
      suicide. The biocontrol Agrobacterium radiobacter K84 secretes the Trojan Horse
      antibiotic agrocin 84 that is selectively transported into the plant pathogen A.
      tumefaciens and processed into the toxin TM84. We previously showed that TM84
      employs a unique tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase
      (LeuRS), while the TM84-producer prevents self-poisoning by expressing a
      resistant LeuRS AgnB2. We now identify a mechanism by which the antibiotic
      producing microbe resists its own toxin. Using a combination of structural,
      biochemical and biophysical approaches, we show that AgnB2 evolved structural
      changes so as to resist the antibiotic by eliminating the tRNA-dependence of TM84
      binding. Mutagenesis of key resistance determinants results in mutants adopting
      an antibiotic-sensitive phenotype. This study illuminates the evolution of
      resistance in self-immunity genes and provides mechanistic insights into a
      fascinating tRNA-dependent antibiotic with applications for the development of
      anti-infectives and the prevention of biocontrol emasculation.

PMID- 27713403
TI  - Scaled laboratory experiments explain the kink behaviour of the Crab Nebula jet.
AB  - The remarkable discovery by the Chandra X-ray observatory that the Crab nebula's
      jet periodically changes direction provides a challenge to our understanding of
      astrophysical jet dynamics. It has been suggested that this phenomenon may be the
      consequence of magnetic fields and magnetohydrodynamic instabilities, but
      experimental demonstration in a controlled laboratory environment has remained
      elusive. Here we report experiments that use high-power lasers to create a plasma
      jet that can be directly compared with the Crab jet through well-defined physical
      scaling laws. The jet generates its own embedded toroidal magnetic fields; as it
      moves, plasma instabilities result in multiple deflections of the propagation
      direction, mimicking the kink behaviour of the Crab jet. The experiment is
      modelled with three-dimensional numerical simulations that show exactly how the
      instability develops and results in changes of direction of the jet.

PMID- 27713404
TI  - Multi-omics integration accurately predicts cellular state in unexplored
      conditions for Escherichia coli.
AB  - A significant obstacle in training predictive cell models is the lack of
      integrated data sources. We develop semi-supervised normalization pipelines and
      perform experimental characterization (growth, transcriptional, proteome) to
      create Ecomics, a consistent, quality-controlled multi-omics compendium for
      Escherichia coli with cohesive meta-data information. We then use this resource
      to train a multi-scale model that integrates four omics layers to predict genome
      wide concentrations and growth dynamics. The genetic and environmental ontology
      reconstructed from the omics data is substantially different and complementary to
      the genetic and chemical ontologies. The integration of different layers confers
      an incremental increase in the prediction performance, as does the information
      about the known gene regulatory and protein-protein interactions. The predictive
      performance of the model ranges from 0.54 to 0.87 for the various omics layers,
      which far exceeds various baselines. This work provides an integrative framework
      of omics-driven predictive modelling that is broadly applicable to guide
      biological discovery.

PMID- 27713406
TI  - Formation of metastable phases by spinodal decomposition.
AB  - Metastable phases may be spontaneously formed from other metastable phases
      through nucleation. Here we demonstrate the spontaneous formation of a metastable
      phase from an unstable equilibrium by spinodal decomposition, which leads to a
      transient coexistence of stable and metastable phases. This phenomenon is generic
      within the recently introduced scenario of the landscape-inversion phase
      transitions, which we experimentally realize as a structural transition in a
      colloidal crystal. This transition exhibits a rich repertoire of new phase
      ordering phenomena, including the coexistence of two equilibrium phases connected
      by two physically different interfaces. In addition, this scenario enables the
      control of sizes and lifetimes of metastable domains. Our findings open a new
      setting that broadens the fundamental understanding of phase-ordering kinetics,
      and yield new prospects of applications in materials science.

PMID- 27713405
TI  - Molecular analysis of aggressive renal cell carcinoma with unclassified histology
      reveals distinct subsets.
AB  - Renal cell carcinomas with unclassified histology (uRCC) constitute a significant
      portion of aggressive non-clear cell renal cell carcinomas that have no standard
      therapy. The oncogenic drivers in these tumours are unknown. Here we perform a
      molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer
      gene sequencing, RNA sequencing, single-nucleotide polymorphism array,
      fluorescence in situ hybridization, immunohistochemistry and cell-based assays.
      We identify recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2
      (18%), BAP1 (13%), KMT2C (10%) and MTOR (8%). Integrated analysis reveals a
      subset of 26% uRCC characterized by NF2 loss, dysregulated Hippo-YAP pathway and
      worse survival, whereas 21% uRCC with mutations of MTOR, TSC1, TSC2 or PTEN and
      hyperactive mTORC1 signalling are associated with better clinical outcome. FH
      deficiency (6%), chromatin/DNA damage regulator mutations (21%) and ALK
      translocation (2%) distinguish additional cases. Altogether, this study reveals
      distinct molecular subsets for 76% of our uRCC cohort, which could have
      diagnostic and therapeutic implications.

PMID- 27713407
TI  - Striatal prediction errors support dynamic control of declarative memory
      decisions.
AB  - Adaptive memory requires context-dependent control over how information is
      retrieved, evaluated and used to guide action, yet the signals that drive
      adjustments to memory decisions remain unknown. Here we show that prediction
      errors (PEs) coded by the striatum support control over memory decisions. Human
      participants completed a recognition memory test that incorporated biased
      feedback to influence participants' recognition criterion. Using model-based
      fMRI, we find that PEs-the deviation between the outcome and expected value of a
      memory decision-correlate with striatal activity and predict individuals' final
      criterion. Importantly, the striatal PEs are scaled relative to memory strength
      rather than the expected trial outcome. Follow-up experiments show that the
      learned recognition criterion transfers to free recall, and targeting biased
      feedback to experimentally manipulate the magnitude of PEs influences criterion
      consistent with PEs scaled relative to memory strength. This provides convergent
      evidence that declarative memory decisions can be regulated via striatally
      mediated reinforcement learning signals.

PMID- 27713408
TI  - Mutually exclusive sense-antisense transcription at FLC facilitates
      environmentally induced gene repression.
AB  - Antisense transcription through genic regions is pervasive in most genomes;
      however, its functional significance is still unclear. We are studying the role
      of antisense transcripts (COOLAIR) in the cold-induced, epigenetic silencing of
      Arabidopsis FLOWERING LOCUS C (FLC), a regulator of the transition to
      reproduction. Here we use single-molecule RNA FISH to address the mechanistic
      relationship of FLC and COOLAIR transcription at the cellular level. We
      demonstrate that while sense and antisense transcripts can co-occur in the same
      cell they are mutually exclusive at individual loci. Cold strongly upregulates
      COOLAIR transcription in an increased number of cells and through the mutually
      exclusive relationship facilitates shutdown of sense FLC transcription in cis.
      COOLAIR transcripts form dense clouds at each locus, acting to influence FLC
      transcription through changed H3K36me3 dynamics. These results may have general
      implications for other loci showing both sense and antisense transcription.

PMID- 27713409
TI  - Evolutionary interplay between sister cytochrome P450 genes shapes plasticity in
      plant metabolism.
AB  - Expansion of the cytochrome P450 gene family is often proposed to have a critical
      role in the evolution of metabolic complexity, in particular in microorganisms,
      insects and plants. However, the molecular mechanisms underlying the evolution of
      this complexity are poorly understood. Here we describe the evolutionary history
      of a plant P450 retrogene, which emerged and underwent fixation in the common
      ancestor of Brassicales, before undergoing tandem duplication in the ancestor of
      Brassicaceae. Duplication leads first to gain of dual functions in one of the
      copies. Both sister genes are retained through subsequent speciation but
      eventually return to a single copy in two of three diverging lineages. In the
      lineage in which both copies are maintained, the ancestral functions are split
      between paralogs and a novel function arises in the copy under relaxed selection.
      Our work illustrates how retrotransposition and gene duplication can favour the
      emergence of novel metabolic functions.

PMID- 27713410
TI  - Abundant DNA 6mA methylation during early embryogenesis of zebrafish and pig.
AB  - DNA N6-methyldeoxyadenosine (6mA) is a well-known prokaryotic DNA modification
      that has been shown to exist and play epigenetic roles in eukaryotic DNA. Here we
      report that 6mA accumulates up to ~0.1-0.2% of total deoxyadenosine during early
      embryogenesis of vertebrates, but diminishes to the background level with the
      progression of the embryo development. During this process a large fraction of
      6mAs locate in repetitive regions of the genome.

PMID- 27713411
TI  - Electronic control of H+ current in a bioprotonic device with Gramicidin A and
      Alamethicin.
AB  - In biological systems, intercellular communication is mediated by membrane
      proteins and ion channels that regulate traffic of ions and small molecules
      across cell membranes. A bioelectronic device with ion channels that control
      ionic flow across a supported lipid bilayer (SLB) should therefore be ideal for
      interfacing with biological systems. Here, we demonstrate a biotic-abiotic
      bioprotonic device with Pd contacts that regulates proton (H+) flow across an SLB
      incorporating the ion channels Gramicidin A (gA) and Alamethicin (ALM). We model
      the device characteristics using the Goldman-Hodgkin-Katz (GHK) solution to the
      Nernst-Planck equation for transport across the membrane. We derive the
      permeability for an SLB integrating gA and ALM and demonstrate pH control as a
      function of applied voltage and membrane permeability. This work opens the door
      to integrating more complex H+ channels at the Pd contact interface to produce
      responsive biotic-abiotic devices with increased functionality.

PMID- 27713412
TI  - Nanoscale probing of electron-regulated structural transitions in silk proteins
      by near-field IR imaging and nano-spectroscopy.
AB  - Silk protein fibres produced by silkworms and spiders are renowned for their
      unparalleled mechanical strength and extensibility arising from their high-beta
      sheet crystal contents as natural materials. Investigation of beta-sheet-oriented
      conformational transitions in silk proteins at the nanoscale remains a challenge
      using conventional imaging techniques given their limitations in chemical
      sensitivity or limited spatial resolution. Here, we report on electron-regulated
      nanoscale polymorphic transitions in silk proteins revealed by near-field
      infrared imaging and nano-spectroscopy at resolutions approaching the molecular
      level. The ability to locally probe nanoscale protein structural transitions
      combined with nanometre-precision electron-beam lithography offers us the
      capability to finely control the structure of silk proteins in two and three
      dimensions. Our work paves the way for unlocking essential nanoscopic protein
      structures and critical conditions for electron-induced conformational
      transitions, offering new rules to design protein-based nanoarchitectures.

PMID- 27713413
TI  - Thermally-nucleated self-assembly of water and alcohol into stable structures at
      hydrophobic interfaces.
AB  - At the interface with solids, the mobility of liquid molecules tends to be
      reduced compared with bulk, often resulting in increased local order due to
      interactions with the surface of the solid. At room temperature, liquids such as
      water and methanol can form solvation structures, but the molecules remain highly
      mobile, thus preventing the formation of long-lived supramolecular assemblies.
      Here we show that mixtures of water with methanol can form a novel type of
      interfaces with hydrophobic solids. Combining in situ atomic force microscopy and
      multiscale molecular dynamics simulations, we identify solid-like two-dimensional
      interfacial structures that nucleate thermally, and are held together by an
      extended network of hydrogen bonds. On graphite, nucleation occurs above ~35 
      degrees C, resulting in robust, multilayered nanoscopic patterns. Our findings
      could have an impact on many fields where water-alcohol mixtures play an
      important role such as fuel cells, chemical synthesis, self-assembly, catalysis
      and surface treatments.

PMID- 27713414
TI  - N-type organic electrochemical transistors with stability in water.
AB  - Organic electrochemical transistors (OECTs) are receiving significant attention
      due to their ability to efficiently transduce biological signals. A major
      limitation of this technology is that only p-type materials have been reported,
      which precludes the development of complementary circuits, and limits sensor
      technologies. Here, we report the first ever n-type OECT, with relatively
      balanced ambipolar charge transport characteristics based on a polymer that
      supports both hole and electron transport along its backbone when doped through
      an aqueous electrolyte and in the presence of oxygen. This new semiconducting
      polymer is designed specifically to facilitate ion transport and promote
      electrochemical doping. Stability measurements in water show no degradation when
      tested for 2 h under continuous cycling. This demonstration opens the possibility
      to develop complementary circuits based on OECTs and to improve the
      sophistication of bioelectronic devices.

PMID- 27713416
TI  - Single-shot observation of optical rogue waves in integrable turbulence using
      time microscopy.
AB  - Optical fibres are favourable tabletop laboratories to investigate both coherent
      and incoherent nonlinear waves. In particular, exact solutions of the one
      dimensional nonlinear Schrodinger equation such as fundamental solitons or
      solitons on finite background can be generated by launching periodic,
      specifically designed coherent waves in optical fibres. It is an open fundamental
      question to know whether these coherent structures can emerge from the nonlinear
      propagation of random waves. However the typical sub-picosecond timescale
      prevented-up to now-time-resolved observations of the awaited dynamics. Here, we
      report temporal 'snapshots' of random light using a specially designed 'time
      microscope'. Ultrafast structures having peak powers much larger than the average
      optical power are generated from the propagation of partially coherent waves in
      optical fibre and are recorded with 250 femtoseconds resolution. Our experiment
      demonstrates the central role played by 'breather-like' structures such as the
      Peregrine soliton in the emergence of heavy-tailed statistics in integrable
      turbulence.

PMID- 27713417
TI  - Social learning strategies modify the effect of network structure on group
      performance.
AB  - The structure of communication networks is an important determinant of the
      capacity of teams, organizations and societies to solve policy, business and
      science problems. Yet, previous studies reached contradictory results about the
      relationship between network structure and performance, finding support for the
      superiority of both well-connected efficient and poorly connected inefficient
      network structures. Here we argue that understanding how communication networks
      affect group performance requires taking into consideration the social learning
      strategies of individual team members. We show that efficient networks outperform
      inefficient networks when individuals rely on conformity by copying the most
      frequent solution among their contacts. However, inefficient networks are
      superior when individuals follow the best member by copying the group member with
      the highest payoff. In addition, groups relying on conformity based on a small
      sample of others excel at complex tasks, while groups following the best member
      achieve greatest performance for simple tasks. Our findings reconcile
      contradictory results in the literature and have broad implications for the study
      of social learning across disciplines.

PMID- 27713415
TI  - Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2.
AB  - Mechanisms of haematopoietic and cardiac patterning remain poorly understood.
      Here we show that the BMP and Wnt signalling pathways are integrated in an
      endoglin (Eng)-dependent manner in cardiac and haematopoietic lineage
      specification. Eng is expressed in early mesoderm and marks both haematopoietic
      and cardiac progenitors. In the absence of Eng, yolk sacs inappropriately express
      the cardiac marker, Nkx2.5. Conversely, high levels of Eng in vitro and in vivo
      increase haematopoiesis and inhibit cardiogenesis. Levels of Eng determine the
      activation of both BMP and Wnt pathways, which are integrated downstream of Eng
      by phosphorylation of Smad1 by Gsk3. By interrogating Eng-dependent Wnt-mediated
      transcriptional changes, we identify Jdp2 as a key Eng-dependent Wnt target,
      sufficient to establish haematopoietic fate in early mesoderm when BMP and Wnt
      crosstalk is disturbed. These studies provide mechanistic insight into the
      integration of BMP and Wnt signalling in the establishment of haematopoietic and
      cardiac progenitors during embryogenesis.

PMID- 27713418
TI  - Papillary thyroid carcinoma with nodular fasciitis-like stroma and beta-catenin
      mutations should be renamed papillary thyroid carcinoma with desmoid-type
      fibromatosis.
AB  - Various histological variants of papillary thyroid carcinoma have been reported,
      some with clinical implications, some with peculiar, sometimes misleading
      morphologies. One of these rare and poorly characterized variants is papillary
      thyroid carcinoma with nodular fasciitis-like stroma, of which fewer than 30
      cases have been documented, mostly as isolated reports. It is a dual tumor
      comprising a malignant epithelial proliferation that harbors typical features of
      conventional papillary thyroid carcinoma, admixed with a prominent mesenchymal
      proliferation resembling nodular fasciitis or fibromatosis. Thus, the terms
      papillary thyroid carcinoma with nodular fasciitis-like stroma and papillary
      thyroid carcinoma with fibromatosis-like stroma are used interchangeably;
      however, the former term suggests a self-limited and regressing disease, whereas
      the latter one suggests a recurrent and potentially aggressive one. Better
      genetic and ultrastructural characterization could lead to more appropriate
      terminology and management. We performed detailed clinicopathological and
      molecular analyses of two cases of PTC with prominent mesenchymal proliferation
      that developed in the thyroid gland of two male patients aged 34 and 48. In both
      cases, the epithelial component harbored a heterozygous somatic activating BRAF
      mutation (p.V600E). Also, in both cases, the mesenchymal component showed typical
      aberrant nuclear and cytoplasmic immunoreactivity for beta-catenin and harbored a
      heterozygous somatic activating mutation in the corresponding CTNNB1 gene
      (p.S45P). This mutation has never been reported in thyroid stroma; in other
      tissues, it is typical of desmoid-type fibromatosis rather than nodular fasciitis
      like stroma. We therefore propose that in cases of papillary thyroid carcinoma
      with a prominent mesenchymal component, mutations in CTNNB1 should be sought;
      when they are present, the term 'papillary thyroid carcinoma with desmoid-type
      fibromatosis' should be used. As the mesenchymal component of these tumors is not
      expected to concentrate radioactive iodine, special considerations apply to
      clinical evaluation and follow-up, which should be brought to the attention of
      the treating specialist.

PMID- 27713420
TI  - Colorectal carcinomas with submucosal invasion (pT1): analysis of
      histopathological and molecular factors predicting lymph node metastasis.
AB  - Submucosally invasive colorectal carcinoma (pT1) has the potential to be cured by
      local excision. In US surgical intervention is reserved for tumors with high
      grade morphology, lymphvascular invasion, and close/positive margin. In other
      countries, particularly Japan, surgical therapy is also recommended for mucinous
      tumors, tumors with >1000 MUm of submucosal invasion, and those with high tumor
      budding. These histological features have not been well evaluated in a western
      cohort of pT1 carcinomas. In a cohort of 116 surgically resected pT1 colorectal
      carcinomas, high tumor budding (P<0.001), lymphatic invasion (P=0.003), depth of
      submucosal invasion >1000 MUm (P=0.04), and high-grade morphology (P=0.04) were
      significantly associated with lymph node metastasis on univariate analysis.
      Mucinous differentiation, tumor location, tumor growth pattern, and size of
      invasive component were not significant. On multivariate analysis, only high
      tumor budding was associated with lymph node metastasis with an odds ratio of 4.3
      (P=0.004). A subset of 48 tumors (22 node-positive and 26 node-negative) was
      analyzed for mutations in 50 oncogenes and tumor suppressors. No statistically
      significant molecular alterations in these 50 genes were associated with lymph
      node status. However, lymphatic invasion was associated with BRAF mutations
      (P=0.01). Furthermore, high tumor budding was associated with mutations in TP53
      (P=0.03) and inversely associated with mutations in the mTOR pathway (PIK3CA and
      AKT, P=0.02). In conclusion, this study demonstrates the importance of
      identifying high tumor budding in pT1 carcinomas when considering additional
      surgical resection. Molecular alterations associated with adverse histological
      features are identified.

PMID- 27713419
TI  - Genetic analysis of microglandular adenosis and acinic cell carcinomas of the
      breast provides evidence for the existence of a low-grade triple-negative breast
      neoplasia family.
AB  - Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas
      microglandular adenosis has been shown to be a neoplastic proliferation. Both
      entities display a triple-negative phenotype, and may give rise to and display
      somatic genomic alterations typical of high-grade triple-negative breast cancers.
      Here we report on a comparison of previously published data on eight carcinoma
      associated microglandular adenosis and eight acinic cell carcinomas subjected to
      targeted massively parallel sequencing targeting all exons of 236 genes
      recurrently mutated in breast cancer and/or DNA repair-related. Somatic
      mutations, insertions/ deletions, and copy number alterations were detected using
      state-of-the-art bioinformatic algorithms. All cases were of triple-negative
      phenotype. A median of 4.5 (1-13) and 4.0 (1-7) non-synonymous somatic mutations
      per carcinoma-associated microglandular adenosis and acinic cell carcinoma were
      identified, respectively. TP53 was the sole highly recurrently mutated gene (75%
      in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53
      mutations were consistently coupled with loss of heterozygosity of the wild-type
      allele. Additional somatic mutations shared by both groups included those in
      BRCA1, PIK3CA, and INPP4B. Recurrent (n=2) somatic mutations restricted to
      microglandular adenosis or acinic cell carcinomas included those affecting PTEN
      and MED12 or ERBB4, respectively. No significant differences in the repertoire of
      somatic mutations were detected between microglandular adenosis and acinic cell
      carcinomas, and between this group of lesions and 77 triple-negative carcinomas
      from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas,
      however, were genetically distinct from estrogen receptor-positive and/or HER2
      positive breast cancers from The Cancer Genome Atlas. Our findings support the
      contention that microglandular adenosis and acinic cell carcinoma are part of the
      same spectrum of lesions harboring frequent TP53 somatic mutations, and likely
      represent low-grade forms of triple-negative disease with no/minimal metastatic
      potential, of which a subset has the potential to progress to high-grade triple
      negative breast cancer.

PMID- 27713422
TI  - Diagnosis of T1 colorectal cancer in pedunculated polyps in daily clinical
      practice: a multicenter study.
AB  - T1 colorectal cancer can be mimicked by pseudo-invasion in pedunculated polyps.
      British guidelines are currently one of the few which recommend diagnostic
      confirmation of T1 colorectal cancer by a second pathologist. The aim of this
      study was to provide insights into the accuracy of histological diagnosis of
      pedunculated T1 colorectal cancer in daily clinical practice. A sample of 128
      cases diagnosed as pedunculated T1 colorectal cancer between 2000 and 2014 from
      10 Dutch hospitals was selected for histological review. Firstly, two Dutch
      expert gastrointestinal pathologists reviewed all hematoxylin-eosin stained
      slides. In 20 cases the diagnosis T1 colorectal cancer was not confirmed (20/128;
      16%). The discordant cases were subsequently discussed with a third Dutch
      gastrointestinal pathologist and a consensus diagnosis was agreed. The revised
      diagnoses were pseudo-invasion in 10 cases (10/128; 8%), high-grade dysplasia in
      4 cases (4/128; 3%), and equivocal in 6 cases (6/128; 5%). To further validate
      the consensus diagnosis, the discordant cases were reviewed by an independent
      expert pathologist from the United Kingdom. A total of 39 cases were reviewed
      blindly including the 20 cases with a revised diagnosis and 19 control cases
      where the Dutch expert panel agreed with the original reporting pathologists
      diagnosis. In 19 of the 20 cases with a revised diagnosis the British pathologist
      agreed that T1 colorectal cancer could not be confirmed. Additionally, amongst
      the 19 control cases the British pathologist was unable to confirm T1 colorectal
      cancer in a further 4 cases and was equivocal in 3 cases. In conclusion, both
      generalist and expert pathologists experience diagnostic difficulty
      distinguishing pseudo-invasion and high-grade dysplasia from T1 colorectal
      cancer. In order to prevent overtreatment, review of the histology of
      pedunculated T1 colorectal cancers by a second pathologist should be considered
      with discussion of these cases at a multidisciplinary meeting.

PMID- 27713421
TI  - Upper tract urothelial carcinomas: frequency of association with mismatch repair
      protein loss and lynch syndrome.
AB  - Increased risk for upper tract urothelial carcinoma is described in patients with
      Lynch syndrome, caused by germline mutations in mismatch repair genes. We aimed
      to identify the frequency of mismatch repair protein loss in upper tract
      urothelial carcinoma and its potential for identifying an association with Lynch
      syndrome. We queried our database to identify upper tract urothelial carcinomas.
      Patients were cross-referenced for history of colorectal carcinoma or other
      common Lynch syndrome-associated neoplasms to enrich for potential Lynch syndrome
      cases. Tumor histopathologic characteristics were reviewed and each case was
      analyzed for loss of mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2, by
      immunohistochemistry. Of 444 patients with upper tract urothelial carcinoma, a
      subset of 215 (encompassing 30 with upper tract urothelial carcinoma and another
      common Lynch syndrome-associated neoplasm) was analyzed for loss of mismatch
      repair protein expression. Of 30 patients with Lynch syndrome-associated
      neoplasms, six had documented Lynch syndrome, including two with Muir-Torre
      syndrome. Mismatch repair protein loss was identified in 7% of total upper tract
      urothelial carcinomas and 30% of patients with Lynch syndrome-associated
      neoplasms (including all patients with Lynch syndrome/Muir-Torre syndrome). Of
      patients without history of Lynch syndrome-associated neoplasms, 5 of 184 (2.7%)
      had loss of mismatch repair protein expression. Twelve cases with mismatch repair
      protein loss demonstrated loss of MSH2 and MSH6, and 2 had isolated loss of MSH6.
      MLH1 and PMS2 expression were consistently retained. Although increased
      intratumoral lymphocytes, inverted growth, pushing tumor-stromal interface, and
      lack of nuclear pleomorphism were more commonly seen in cases with mismatch
      repair protein loss, only intratumoral lymphocytes and presence of pushing
      borders were statistically significant. MLH1 and PMS2 testing appear to have
      little utility in upper tract urothelial carcinoma; however, mismatch repair
      protein loss of MSH2 and/or MSH6 by immunohistochemistry seems relatively
      sensitive and specific for identifying patients with potential Lynch syndrome.

PMID- 27713423
TI  - Downregulation of acetyl-CoA synthetase 2 is a metabolic hallmark of tumor
      progression and aggressiveness in colorectal carcinoma.
AB  - Acetyl-CoA synthetase-2 is an emerging key enzyme for cancer metabolism, which
      supplies acetyl-CoA for tumor cells by capturing acetate as a carbon source under
      stressed conditions. However, implications of acetyl-CoA synthetase-2 in
      colorectal carcinoma may differ from other malignancies, because normal
      colonocytes use short-chain fatty acids as an energy source, which are supplied
      by fermentation of the intestinal flora. Here we analyzed acetyl-CoA synthetase-2
      mRNA expression by reverse-transcription quantitative PCR in paired normal mucosa
      and tumor tissues of 12 colorectal carcinomas, and subsequently evaluated acetyl
      CoA synthetase-2 protein expression by immunohistochemistry in 157 premalignant
      colorectal lesions, including 60 conventional adenomas and 97 serrated polyps,
      1,106 surgically resected primary colorectal carcinomas, and 23 metastatic
      colorectal carcinomas in the liver. In reverse-transcription quantitative PCR
      analysis, acetyl-CoA synthetase-2 mRNA expression was significantly decreased in
      tumor tissues compared with corresponding normal mucosa tissues. In acetyl-CoA
      synthetase-2 immunohistochemistry analysis, all 157 colorectal polyps showed
      moderate-to-strong expression of acetyl-CoA synthetase-2. However, cytoplasmic
      acetyl-CoA synthetase-2 expression was downregulated (acetyl-CoA synthetase-2 low
      expression) in 771 (69.7%) of 1,106 colorectal carcinomas and 21 (91.3%) of 23
      metastatic lesions. The colorectal carcinomas with acetyl-CoA synthetase-2-low
      expression were significantly associated with advanced TNM stage, poor
      differentiation, and frequent tumor budding. Regarding the molecular aspect,
      acetyl-CoA synthetase-2-low expression exhibited a tendency of frequent KRT7
      expression and decreased KRT20 and CDX2 expression. In survival analysis, acetyl
      CoA synthetase-2-low expression was an independent prognostic factor for poor 5
      year progression-free survival (hazard ratio, 1.39; 95% confidence interval, 1.08
      1.79; P=0.01). In conclusion, these findings suggest that downregulation of
      acetyl-CoA synthetase-2 expression is a metabolic hallmark of tumor progression
      and aggressive behavior in colorectal carcinoma.

PMID- 27713424
TI  - 5-Hydroxymethylcytosine is an independent predictor of survival in malignant
      melanoma.
AB  - Outcomes for melanoma patients vary within cancer stage. Prognostic biomarkers
      are potential adjuncts to provide more precise prognostic information. Simple,
      low-cost biomarker assays, such as those based on immunohistochemistry, have
      strong translational potential. 5-hydroxymethylcytosine (5 hmC) shows prognostic
      potential in melanoma but prior studies were small. We, therefore, analysed 5 hmC
      in a retrospective cohort to provide external validation of its prognostic value.
      Two hundred primary melanomas were evaluated for 5 hmC expression using
      immunohistochemistry. The primary objective was to assess the effect on overall
      survival while controlling for important confounders. Univariable and
      multivariable analyses were performed. REMARK guidelines were followed. The 5 hmC
      immunohistochemistry scoring showed very strong inter-observer agreement (ICC
      0.88) and expression was significantly related to age, site, Breslow thickness,
      ulceration, mitotic rate, and stage. Kaplan-Meier analysis showed 5 hmC was
      associated with metastasis-free, melanoma-specific, and overall survival,
      P<0.0001 for each. In univariable Cox proportional hazards models, 5 hmC hazard
      ratios were significant and remained so in a multivariable model. A two-step cox
      model was created using stage and 5 hmC, as stage is the gold standard for
      clinical practice. The addition of 5 hmC produced significant improvement in the
      model and 5 hmC and stage were independent significant predictors. This is the
      largest study of the prognostic value of 5 hmC immunohistochemistry in melanoma.
      The 5 hmC scoring was easily and reproducibly performed and it was an independent
      predictor of metastasis-free survival, melanoma-specific survival, and overall
      survival. This work supports further development of 5 hmC as a prognostic
      biomarker and suggests that it could add more precision to American Joint
      Committee on Cancer staging.

PMID- 27713426
TI  - Orbital disproportionation of electronic density is a universal feature of alkali
      doped fullerides.
AB  - Alkali-doped fullerides show a wide range of electronic phases in function of
      alkali atoms and the degree of doping. Although the presence of strong electron
      correlations is well established, recent investigations also give evidence for
      dynamical Jahn-Teller instability in the insulating and the metallic trivalent
      fullerides. In this work, to reveal the interplay of these interactions in
      fullerides with even electrons, we address the electronic phase of tetravalent
      fulleride with accurate many-body calculations within a realistic electronic
      model including all basic interactions extracted from first principles. We find
      that the Jahn-Teller instability is always realized in these materials too. In
      sharp contrast to the correlated metals, tetravalent system displays uncorrelated
      band-insulating state despite similar interactions present in both fullerides.
      Our results show that the Jahn-Teller instability and the accompanying orbital
      disproportionation of electronic density in the degenerate lowest unoccupied
      molecular orbital band is a universal feature of fullerides.

PMID- 27713425
TI  - Bimodal antagonism of PKA signalling by ARHGAP36.
AB  - Protein kinase A is a key mediator of cAMP signalling downstream of G-protein
      coupled receptors, a signalling pathway conserved in all eukaryotes. cAMP binding
      to the regulatory subunits (PKAR) relieves their inhibition of the catalytic
      subunits (PKAC). Here we report that ARHGAP36 combines two distinct inhibitory
      mechanisms to antagonise PKA signalling. First, it blocks PKAC activity via a
      pseudosubstrate motif, akin to the mechanism employed by the protein kinase
      inhibitor proteins. Second, it targets PKAC for rapid ubiquitin-mediated
      lysosomal degradation, a pathway usually reserved for transmembrane receptors.
      ARHGAP36 thus dampens the sensitivity of cells to cAMP. We show that PKA
      inhibition by ARHGAP36 promotes derepression of the Hedgehog signalling pathway,
      thereby providing a simple rationale for the upregulation of ARHGAP36 in
      medulloblastoma. Our work reveals a new layer of PKA regulation that may play an
      important role in development and disease.

PMID- 27713431
TI  - Antibiotic resistance: Correct dosage.

PMID- 27713428
TI  - Sensory feedback synchronizes motor and sensory neuronal networks in the neonatal
      rat spinal cord.
AB  - Early stages of sensorimotor system development in mammals are characterized by
      the occurrence of spontaneous movements. Whether and how these movements support
      correlated activity in developing sensorimotor spinal cord circuits remains
      unknown. Here we show highly correlated activity in sensory and motor zones in
      the spinal cord of neonatal rats in vivo. Both during twitches and complex
      movements, movement-generating bursts in motor zones are followed by bursts in
      sensory zones. Deafferentation does not affect activity in motor zones and
      movements, but profoundly suppresses activity bursts in sensory laminae and
      results in sensorimotor uncoupling, implying a primary role of sensory feedback
      in sensorimotor synchronization. This is further supported by largely dissociated
      activity in sensory and motor zones observed in the isolated spinal cord in
      vitro. Thus, sensory feedback resulting from spontaneous movements is
      instrumental for coordination of activity in developing sensorimotor spinal cord
      circuits.

PMID- 27713432
TI  - Orthodontic therapists - has their introduction affected outcomes?
AB  - Objective To assess the effect of the introduction of orthodontic therapists
      (OTs) on the quality of orthodontic treatment outcomes in two specialist
      orthodontic practices in the UK.Study design Retrospective cross sectional
      observational study.Setting Multi-centre evaluation at two specialist orthodontic
      practices in Yorkshire. Data collection was carried out during 2014.Materials and
      methods The treatment undertaken by three specialist orthodontic clinicians (A, B
      and C) was evaluated at two time points. The first time point (T1) was before the
      introduction of OTs when the specialist orthodontic clinicians were solo
      operators. The second time point (T2) followed the introduction of OTs. Patients
      at T2 had their treatment planned by a specialist orthodontist and were seen for
      care by both the orthodontist and an OT who had been qualified for a minimum of
      three years. A sample size of 30 orthodontic patients per clinician at each time
      point was chosen. Included participants had completed a course of fixed appliance
      therapy. They were consecutively selected from cases that had been completed in
      the specified time frame for each clinician.Main outcome measures The quality of
      treatment was assessed objectively using the quantitative Peer Assessment Rating
      index (PAR index). Data extracted from the specialist practice databases also
      allowed conclusions to be drawn about the length of treatment time and number of
      appointments in each treatment group.Results and conclusions There appears to
      have been no change in orthodontic treatment outcomes following the introduction
      of supervised OTs at two specialist orthodontic practices.

PMID- 27713429
TI  - Disaggregating the evidence linking biodiversity and ecosystem services.
AB  - Ecosystem services (ES) are an increasingly popular policy framework for
      connecting biodiversity with human well-being. These efforts typically assume
      that biodiversity and ES covary, but the relationship between them remains
      remarkably unclear. Here we analyse >500 recent papers and show that reported
      relationships differ among ES, methods of measuring biodiversity and ES, and
      three different approaches to linking them (spatial correlations, management
      comparisons and functional experiments). For spatial correlations, biodiversity
      relates more strongly to measures of ES supply than to resulting human benefits.
      For management comparisons, biodiversity of 'service providers' predicts ES more
      often than biodiversity of functionally unrelated taxa, but the opposite is true
      for spatial correlations. Functional experiments occur at smaller spatial scales
      than management and spatial studies, which show contrasting responses to scale.
      Our results illuminate the varying dynamics relating biodiversity to ES, and show
      the importance of matching management efforts to the most relevant scientific
      evidence.

PMID- 27713435
TI  - Mind the gap: Are dental trainees satisfied with their clinical experience?
AB  - An investigation of the clinical experiences of dentists within the national
      dental foundation training programme in the North West of England.

PMID- 27713427
TI  - Insulin and TOR signal in parallel through FOXO and S6K to promote epithelial
      wound healing.
AB  - The TOR and Insulin/IGF signalling (IIS) network controls growth, metabolism and
      ageing. Although reducing TOR or insulin signalling can be beneficial for ageing,
      it can be detrimental for wound healing, but the reasons for this difference are
      unknown. Here we show that IIS is activated in the cells surrounding an epidermal
      wound in Drosophila melanogaster larvae, resulting in PI3K activation and
      redistribution of the transcription factor FOXO. Insulin and TOR signalling are
      independently necessary for normal wound healing, with FOXO and S6K as their
      respective effectors. IIS is specifically required in cells surrounding the
      wound, and the effect is independent of glycogen metabolism. Insulin signalling
      is needed for the efficient assembly of an actomyosin cable around the wound, and
      constitutively active myosin II regulatory light chain suppresses the effects of
      reduced IIS. These findings may have implications for the role of insulin
      signalling and FOXO activation in diabetic wound healing.

PMID- 27713436
TI  - Information regarding restorative dentistry for new graduates.
AB  - A recent national survey has shown the need for clarification regarding the
      various disciplines encompassed by restorative dentistry and their respective
      training pathways. This document aims to address this by outlining the remit of
      restorative dentistry, in addition to the various job roles involved. This
      information is being disseminated by the British Society for Restorative
      Dentistry, and given the relevance to referrers and those looking for insight
      into the speciality, it has been reproduced here. Roles within the speciality
      range from dentists with special interests to specialists and consultants,
      whether primarily academic or clinical. The choice that a new graduate may make
      to choose a specific route will likely depend on a number of factors, often
      specific to each individual. Guidance on ways to gain experience and sources of
      further information are also provided.

PMID- 27713437
TI  - Snap, send &screen.
AB  - Validity and reliability of remote dental screening of different dental
      professionals using a store-and-forward telehealth model.

PMID- 27713438
TI  - No bad thing.

PMID- 27713440
TI  - OMFS: Gender imbalance?

PMID- 27713441
TI  - Conference report: ADI Young Dentist Implant Day.

PMID- 27713444
TI  - New radiation safety guidance launched.

PMID- 27713443
TI  - Dental education: Reviewing the situation.

PMID- 27713446
TI  - Student view: 'My passion for dentistry has only got stronger'.

PMID- 27713447
TI  - What difference do orthodontic therapists make to outcomes?
AB  - Orthodontic therapists - has their introduction affected Orthodontic Peer
      Assessment Rating (PAR) outcomes?

PMID- 27713448
TI  - The orthodontic condition of children in England, Wales and Northern Ireland
      2013.
AB  - Background The 2013 Children's Dental Health Survey is the fifth in a series of
      national surveys.Aims This paper reports the orthodontic condition of 12- and 15
      year-olds and how they and their parents feel about the appearance of their
      teeth.Methodology A representative sample of children (5y, 8y, 12y, 15y) in
      England, Wales and Northern Ireland were invited to participate in dental
      examinations. A modified Index of Orthodontic Treatment Need (IOTN) was used as a
      measure of orthodontic treatment need for 12- and 15-year-olds. Children and
      parents were invited to complete a questionnaire about oral health behaviour and
      attitudes.Results Nine percent of 12-year-olds and 18% of 15-year-olds were
      undergoing orthodontic treatment at the time of the survey. Forty-four percent of
      12-year-olds and 29% of 15-year-olds expressed a desire for straighter teeth,
      however over half of this group would not qualify for NHS treatment. Unmet
      treatment need was higher in children eligible for free school meals (P <0.05 at
      15y).Conclusions Provision of and demand for orthodontic treatment is increasing,
      with a significant proportion of children who desire orthodontic care not
      eligible to receive it. Children from deprived backgrounds have greater unmet
      orthodontic treatment need.

PMID- 27713451
TI  - Ecological hypothesis of dentin and root caries.
AB  - '...questionable whether bacteria play a role in the initial stages of the
      degradation of the organic components of teeth.'

PMID- 27713449
TI  - Validity and reliability of remote dental screening by different oral health
      professionals using a store-and-forward telehealth model.
AB  - Objective This study was conducted to evaluate the validity and reliability of
      intraoral photographic assessments by different members of a dental team as a
      means for dental screening in children.Methods The intraoral photographic records
      of 126 children (2 to 18 years old) were obtained from routine clinical records
      taken before dental treatment. Intraoral photographs were obtained using a DSLR
      camera and then uploaded to a cloud-based server using store-and-forward
      telehealth technology. Images were reviewed by an expert panel to formulate a
      benchmark screening baseline, to which the screeners' data were compared. The
      photographic assessments conducted by a mid-level dental practitioner (MLDP) and
      dentist, were compared to the benchmark expert panel assessment.Results The
      screeners' assessments by means of intraoral photography, when compared to the
      expert panel assessment had a sensitivity value of 82-89% and specificity value
      of 97%. The inter-examiner agreement between the expert panel assessment and
      photographic method (assessed by a dentist and MLDP), was almost perfect, with a
      kappa score ranging from 0.82 to 0.88. The mean DFT/dft score for the children as
      determined by the expert panel's review and photographic assessment ranging from
      5.41 to 5.79, with mean scores between the two assessment methods not
      significantly different (P = 0.746).Conclusion Our results suggested that oral
      health professionals (other than dentists) have the potential to screen for
      caries from intraoral photographs with the same diagnostic accuracy and
      reliability as dentists. This strategy has implications for supporting the use of
      MLDPs such as dental therapists or hygienists to screen for oral disease using
      telehealth.

PMID- 27713453
TI  - Lack of buffering by composites promotes shift to more cariogenic bacteria.
AB  - Amalgam shows the highest acid-buffering ability and antibacterial effect.

PMID- 27713454
TI  - Posterior bulk-filled resin composite restorations: a 5-year randomized
      controlled clinical study.
AB  - No better clinical outcome for bulk-filled resin composites.

PMID- 27713455
TI  - Dundee dentists pilot public health coaching in prison.

PMID- 27713457
TI  - Randomized clinical trial on arresting dental root caries through silver diamine
      fluoride applications in community-dwelling elders.
AB  - The immediate application of potassium iodide to dental root caries treated with
      silver diamine fluoride improved the colour of the lesion from black to bright
      yellow, but this colour change was only short lived.

PMID- 27713461
TI  - Oral health: Flossing has to be taught well.

PMID- 27713460
TI  - Dens invaginatus: diagnosis and management strategies.
AB  - Dens invaginatus is a developmental malformation, in which there is an infolding
      of enamel into dentine. These infolds represent stagnation sites for bacteria and
      can predispose to dental caries. The carious infection can spread via enamel and
      dentine to contaminate the pulp and cause soft tissue necrosis. The altered and
      sometimes complex anatomy of affected teeth can make endodontic management
      challenging. Early diagnosis is therefore essential as prophylactic treatment of
      the dens can prevent degeneration and pulpal necrosis. The aim of this article is
      to review the aetiology, classification, diagnosis and management of teeth
      affected with dens invaginatus. Emphasis will be placed on describing the
      clinical features of this anomaly. Treatment options, management strategies and
      the challenges faced in managing this condition will be discussed.

PMID- 27713462
TI  - The growing problems of dental caries and obesity: an Australian perspective.
AB  - Preventable diet-related diseases such as dental caries and obesity are a growing
      global problem, causing a significant burden on public health systems. Although
      there has been good evidence for the links between sugar consumption and dental
      caries for many decades, we are now seeing stronger links implicating sugar in
      obesity. There is a growing worldwide movement to tackle these problems by
      targeting the consumption of sugar-sweetened beverages through a range of public
      policy measures.

PMID- 27713466
TI  - Orthodontics: Irresponsible articles.

PMID- 27713467
TI  - An inspiring specialty.

PMID- 27713464
TI  - Restorative complications of orthodontic treatment.
AB  - The complications of elective orthodontic treatment are numerous. Patients need
      to be aware, in advance, of possible problems including resorption, instability,
      caries, recession and failure to deliver optimal tooth position. The investment
      of time and resources by all concerned is considerable and if there are adverse
      outcomes these can be biologically costly in the longer term. A frank and full
      discussion of the possible problems is necessary following the findings of
      Montgomery vs. Lanarkshire in 2015.

PMID- 27713469
TI  - Fast sintering of silver nanoparticle and flake layers by infrared module
      assistance in large area roll-to-roll gravure printing system.
AB  - We present fast sintering for silver (Ag) nanoparticle (NP) and flake layers
      printed using roll-to-roll (R2R) gravure printing. An infrared (IR) sintering
      module was applied to an R2R system to shorten the sintering duration of an R2R
      gravure-printed Ag layer. IR sintering of the conductive layer was improved by
      optimising the process condition. After printing of the Ag NP and Ag flake
      layers, additional IR sintering was performed in the R2R system. The lowest sheet
      resistance obtained in the Ag NP layer was 0.294 Omega/?, the distance between
      the substrate and lamp was 50-mm long, the IR lamp power was 500 W, and the
      sintering time was 5.4 s. The fastest sintering of 0.34 Omega/? was achieved with
      50-mm distance, 1,000-W IR lamp power, and 1.08-s sintering time. In the Ag flake
      layer, the lowest sheet resistance obtained was 0.288 Omega/? with a 20-mm
      distance, 1,000-W IR lamp power, and 10.8-s sintering time. Meanwhile, the
      fastest sintering was obtained with a 3.83 Omega/? sheet resistance, 20-mm
      distance, 1000-W IR lamp, and 1.08-s sintering time. Thus, the IR sintering
      module can easily be employed in an R2R system to obtain excellent layer sheet
      resistance.

PMID- 27713472
TI  - Real internal microstructure based key mechanism analysis on the micro-damage
      process of short fibre-reinforced composites.
AB  - In this work, the underlying micro-damage mechanisms of randomly oriented short
      fibre-reinforced composites were revealed based on real internal microstructural
      characteristics obtained by high-resolution (0.7 MUm/pixel) synchrotron radiation
      X-ray computed tomography (SR-CT). The special 'pore dominant micro-damage
      processes' were directly observed through SR-CT three-dimensional reconstructed
      images, which were different from the well-known 'fibre breakage dominant failure
      mode'. The mechanisms of pore formation and pore evolution were further
      investigated on the basis of the microstructural parameters extracted from the SR
      CT results. On one hand, the pore formation mechanism caused by shear stress
      concentration was proposed by combining the shear-lag model with the
      microstructural parameters obtained from the experiment, including the fibre
      length and orientation angle. On the other hand, the 'fibre-end aggregation
      induced pore connection' mode of crack initiation was proposed through a
      composites model, which considered the parameters of real internal
      microstructure, including the critical value of the distance between neighbouring
      fibre ends and the number of neighbouring fibre ends. The study indicated that
      the shear stress concentration was significant in the region with a large number
      of neighbouring fibre ends, thus causing pore connection and crack initiation.

PMID- 27713470
TI  - In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle.
AB  - Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies
      suggests similar subtle fluctuations in hippocampal structure, predominantly
      linked to estrogen. Hippocampal abnormalities have been observed in several
      neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential
      impact of subtle sex-hormonal fluctuations on human hippocampal structure in
      health is unclear. We tested the feasibility of longitudinal neuroimaging in
      conjunction with rigorous menstrual cycle monitoring to evaluate potential
      changes in hippocampal microstructure associated with physiological sex-hormonal
      changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy
      female subject were acquired across two full menstrual cycles. We calculated
      hippocampal fractional anisotropy (FA), a measure sensitive to changes in
      microstructural integrity, and investigated potential correlations with estrogen.
      We observed a significant positive correlation between FA values and estrogen in
      the hippocampus bilaterally, revealing a peak in FA closely paralleling
      ovulation. This exploratory, single-subject study demonstrates the feasibility of
      a longitudinal DWI scanning protocol across the menstrual cycle and is the first
      to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In
      light of recent attempts to neurally phenotype single humans, our findings
      highlight menstrual cycle monitoring in parallel with highly sampled individual
      neuroimaging data to address fundamental questions about the dynamics of
      plasticity in the adult brain.

PMID- 27713474
TI  - Carbon-Coated, Diatomite-Derived Nanosilicon as a High Rate Capable Li-ion
      Battery Anode.
AB  - Silicon is produced in a variety of ways as an ultra-high capacity lithium-ion
      battery (LIB) anode material. The traditional carbothermic reduction process
      required is expensive and energy-intensive; in this work, we use an efficient
      magnesiothermic reduction to convert the silica-based frustules within
      diatomaceous earth (diatomite, DE) to nanosilicon (nanoSi) for use as LIB anodes.
      Polyacrylic acid (PAA) was used as a binder for the DE-based nanoSi anodes for
      the first time, being attributed for the high silicon utilization under high
      current densities (up to 4C). The resulting nanoSi exhibited a high BET specific
      surface area of 162.6 cm2 g-1, compared to a value of 7.3 cm2 g-1 for the
      original DE. DE contains SiO2 architectures that make ideal bio-derived templates
      for nanoscaled silicon. The DE-based nanoSi anodes exhibit good cyclability, with
      a specific discharge capacity of 1102.1 mAh g-1 after 50 cycles at a C-rate of
      C/5 (0.7 A gSi-1) and high areal loading (2 mg cm-2). This work also demonstrates
      the fist rate capability testing for a DE-based Si anode; C-rates of C/30 - 4C
      were tested. At 4C (14.3 A gSi-1), the anode maintained a specific capacity of
      654.3 mAh g-1 - nearly 2x higher than graphite's theoretical value (372 mAh g-1).

PMID- 27713473
TI  - Identification of the nuclear localisation signal of O-GlcNAc transferase and its
      nuclear import regulation.
AB  - Nucleocytoplasmic O-GlcNAc transferase (OGT) attaches a single GlcNAc to hydroxyl
      groups of serine and threonine residues. Although the cellular localisation of
      OGT is important to regulate a variety of cellular processes, the molecular
      mechanisms regulating the nuclear localisation of OGT is unclear. Here, we
      characterised three amino acids (DFP; residues 451-453) as the nuclear
      localisation signal of OGT and demonstrated that this motif mediated the nuclear
      import of non-diffusible beta-galactosidase. OGT bound the importin alpha5
      protein, and this association was abolished when the DFP motif of OGT was mutated
      or deleted. We also revealed that O-GlcNAcylation of Ser389, which resides in the
      tetratricopeptide repeats, plays an important role in the nuclear localisation of
      OGT. Our findings may explain how OGT, which possesses a NLS, exists in the
      nucleus and cytosol simultaneously.

PMID- 27713471
TI  - Hepatic Deletion of Janus Kinase 2 Counteracts Oxidative Stress in Mice.
AB  - Genetic deletion of the tyrosine kinase JAK2 or the downstream transcription
      factor STAT5 in liver impairs growth hormone (GH) signalling and thereby promotes
      fatty liver disease. Hepatic STAT5 deficiency accelerates liver tumourigenesis in
      presence of high GH levels. To determine whether the upstream kinase JAK2 exerts
      similar functions, we crossed mice harbouring a hepatocyte-specific deletion of
      JAK2 (JAK2Deltahep) to GH transgenic mice (GHtg) and compared them to
      GHtgSTAT5Deltahep mice. Similar to GHtgSTAT5Deltahep mice, JAK2 deficiency
      resulted in severe steatosis in the GHtg background. However, in contrast to
      STAT5 deficiency, loss of JAK2 significantly delayed liver tumourigenesis. This
      was attributed to: (i) activation of STAT3 in STAT5-deficient mice, which was
      prevented by JAK2 deficiency and (ii) increased detoxification capacity of JAK2
      deficient livers, which diminished oxidative damage as compared to
      GHtgSTAT5Deltahep mice, despite equally severe steatosis and reactive oxygen
      species (ROS) production. The reduced oxidative damage in JAK2-deficient livers
      was linked to increased expression and activity of glutathione S-transferases
      (GSTs). Consistent with genetic deletion of Jak2, pharmacological inhibition and
      siRNA-mediated knockdown of Jak2 led to significant upregulation of Gst isoforms
      and to reduced hepatic oxidative DNA damage. Therefore, blocking JAK2 function
      increases detoxifying GSTs in hepatocytes and protects against oxidative liver
      damage.

PMID- 27713475
TI  - Recent origin and semi-permeable species boundaries in the scleractinian coral
      genus Stylophora from the Red Sea.
AB  - Reticulate evolution, introgressive hybridisation, and phenotypic plasticity have
      been documented in scleractinian corals and have challenged our ability to
      interpret speciation processes. Stylophora is a key model system in coral biology
      and physiology, but genetic analyses have revealed that cryptic lineages
      concealed by morphological stasis exist in the Stylophora pistillata species
      complex. The Red Sea represents a hotspot for Stylophora biodiversity with six
      morphospecies described, two of which are regionally endemic. We investigated
      Stylophora species boundaries from the Red Sea and the associated Symbiodinium by
      sequencing seven DNA loci. Stylophora morphospecies from the Red Sea were not
      resolved based on mitochondrial phylogenies and showed nuclear allele sharing.
      Low genetic differentiation, weak isolation, and strong gene flow were found
      among morphospecies although no signals of genetic recombination were evident
      among them. Stylophora mamillata harboured Symbiodinium clade C whereas the other
      two Stylophora morphospecies hosted either Symbiodinium clade A or C. These
      evolutionary patterns suggest that either gene exchange occurs through reticulate
      evolution or that multiple ecomorphs of a phenotypically plastic species occur in
      the Red Sea. The recent origin of the lineage leading to the Red Sea Stylophora
      may indicate an ongoing speciation driven by environmental changes and incomplete
      lineage sorting.

PMID- 27713476
TI  - The fates of 15N-labeled fertilizer in a wheat-soil system as influenced by
      fertilization practice in a loamy soil.
AB  - Appropriate fertilization practice is crucial to achieve maximum wheat grain
      yield with minimum nitrogen (N) loss. A field 15N micro-plot experiment was
      conducted to determine the effects of application methods [split application (SA)
      and band application (BA)] and N rates (60, 150 and 240 kg ha-1) on the wheat
      grain yield, urea-15N fate and N efficiency in Jiangyan County, China. At high N
      rates, wheat grain yield was significantly higher for SA than BA treatment, but
      there was no difference at the lower N rates. Plant N derived from fertilizer was
      higher in SA than in BA treatment. The high N fertilizer application increased
      total N uptake by wheat derived from fertilizer, but wheat plant N derived from
      soil was not affected by the N rate. Fertilizer-N recovery in SA treatment was
      higher than in BA treatment. Residual N recovery in the 0-80 cm soil layer was 31
      51%, which decreased with increasing N rate. The highest N loss was found for BA
      treatment at the N application of 240 kg ha-1. The one-time BA of N fertilizer,
      especially for higher N rates, led to reduced wheat grain yield and N efficiency,
      and increased the N loss.

PMID- 27713478
TI  - Polymer-dispersed liquid crystal elastomers.
AB  - The need for mechanical manipulation during the curing of conventional liquid
      crystal elastomers diminishes their applicability in the field of shape
      programmable soft materials and future applications in additive manufacturing.
      Here we report on polymer-dispersed liquid crystal elastomers, novel composite
      materials that eliminate this difficulty. Their thermal shape memory anisotropy
      is imprinted by curing in external magnetic field, providing for conventional
      moulding of macroscopically sized soft, thermomechanically active elastic objects
      of general shapes. The binary soft-soft composition of isotropic elastomer
      matrix, filled with freeze-fracture-fabricated, oriented liquid crystal elastomer
      microparticles as colloidal inclusions, allows for fine-tuning of thermal
      morphing behaviour. This is accomplished by adjusting the concentration, spatial
      distribution and orientation of microparticles or using blends of microparticles
      with different thermomechanical characteristics. We demonstrate that any Gaussian
      thermomechanical deformation mode (bend, cup, saddle, left and right twist) of a
      planar sample, as well as beat-like actuation, is attainable with bilayer
      microparticle configurations.

PMID- 27713477
TI  - Antiestrogen Resistant Cell Lines Expressing Estrogen Receptor alpha Mutations
      Upregulate the Unfolded Protein Response and are Killed by BHPI.
AB  - Outgrowth of metastases expressing ERalpha mutations Y537S and D538G is common
      after endocrine therapy for estrogen receptor alpha (ERalpha) positive breast
      cancer. The effect of replacing wild type ERalpha in breast cancer cells with
      these mutations was unclear. We used the CRISPR-Cas9 genome editing system and
      homology directed repair to isolate and characterize 14 T47D cell lines in which
      ERalphaY537S or ERalphaD538G replace one or both wild-type ERalpha genes. In 2
      dimensional, and in quantitative anchorage-independent 3-dimensional cell
      culture, ERalphaY537S and ERalphaD538G cells exhibited estrogen-independent
      growth. A progestin further increased their already substantial proliferation in
      micromolar 4-hydroxytamoxifen and fulvestrant/ICI 182,780 (ICI). Our recently
      described ERalpha biomodulator, BHPI, which hyperactivates the unfolded protein
      response (UPR), completely blocked proliferation. In ERalphaY537S and
      ERalphaD538G cells, estrogen-ERalpha target genes were constitutively active and
      partially antiestrogen resistant. The UPR marker sp-XBP1 was constitutively
      activated in ERalphaY537S cells and further induced by progesterone in both cell
      lines. UPR-regulated genes associated with tamoxifen resistance, including the
      oncogenic chaperone BiP/GRP78, were upregulated. ICI displayed a greater than 2
      fold reduction in its ability to induce ERalphaY537S and ERalphaD538G
      degradation. Progestins, UPR activation and perhaps reduced ICI-stimulated
      ERalpha degradation likely contribute to antiestrogen resistance seen in
      ERalphaY537S and ERalphaD538G cells.

PMID- 27713479
TI  - Intrinsic noise and deviations from criticality in Boolean gene-regulatory
      networks.
AB  - Gene regulatory networks can be successfully modeled as Boolean networks. A much
      discussed hypothesis says that such model networks reproduce empirical findings
      the best if they are tuned to operate at criticality, i.e. at the borderline
      between their ordered and disordered phases. Critical networks have been argued
      to lead to a number of functional advantages such as maximal dynamical range,
      maximal sensitivity to environmental changes, as well as to an excellent tradeoff
      between stability and flexibility. Here, we study the effect of noise within the
      context of Boolean networks trained to learn complex tasks under supervision. We
      verify that quasi-critical networks are the ones learning in the fastest possible
      way -even for asynchronous updating rules- and that the larger the task
      complexity the smaller the distance to criticality. On the other hand, when
      additional sources of intrinsic noise in the network states and/or in its wiring
      pattern are introduced, the optimally performing networks become clearly
      subcritical. These results suggest that in order to compensate for inherent
      stochasticity, regulatory and other type of biological networks might become
      subcritical rather than being critical, all the most if the task to be performed
      has limited complexity.

PMID- 27713480
TI  - The transcription factor Ets21C drives tumor growth by cooperating with AP-1.
AB  - Tumorigenesis is driven by genetic alterations that perturb the signaling
      networks regulating proliferation or cell death. In order to block tumor growth,
      one has to precisely know how these signaling pathways function and interplay.
      Here, we identified the transcription factor Ets21C as a pivotal regulator of
      tumor growth and propose a new model of how Ets21C could affect this process. We
      demonstrate that a depletion of Ets21C strongly suppressed tumor growth while
      ectopic expression of Ets21C further increased tumor size. We confirm that Ets21C
      expression is regulated by the JNK pathway and show that Ets21C acts via a
      positive feed-forward mechanism to induce a specific set of target genes that is
      critical for tumor growth. These genes are known downstream targets of the JNK
      pathway and we demonstrate that their expression not only depends on the
      transcription factor AP-1, but also on Ets21C suggesting a cooperative
      transcriptional activation mechanism. Taken together we show that Ets21C is a
      crucial player in regulating the transcriptional program of the JNK pathway and
      enhances our understanding of the mechanisms that govern neoplastic growth.

PMID- 27713481
TI  - Computational prediction shines light on type III secretion origins.
AB  - Type III secretion system is a key bacterial symbiosis and pathogenicity
      mechanism responsible for a variety of infectious diseases, ranging from food
      borne illnesses to the bubonic plague. In many Gram-negative bacteria, the type
      III secretion system transports effector proteins into host cells, converting
      resources to bacterial advantage. Here we introduce a computational method that
      identifies type III effectors by combining homology-based inference with de novo
      predictions, reaching up to 3-fold higher performance than existing tools. Our
      work reveals that signals for recognition and transport of effectors are
      distributed over the entire protein sequence instead of being confined to the N
      terminus, as was previously thought. Our scan of hundreds of prokaryotic genomes
      identified previously unknown effectors, suggesting that type III secretion may
      have evolved prior to the archaea/bacteria split. Crucially, our method performs
      well for short sequence fragments, facilitating evaluation of microbial
      communities and rapid identification of bacterial pathogenicity - no genome
      assembly required. pEffect and its data sets are available at
      http://services.bromberglab.org/peffect.

PMID- 27713482
TI  - Understanding the multiferroicity in TmMn2O5 by a magnetically induced
      ferrielectric model.
AB  - The magnetically induced electric polarization behaviors in multiferroic TmMn2O5
      in response to varying temperature and magnetic field are carefully investigated
      by means of a series of characterizations including the high precision
      pyroelectric current technique. Here polycrystalline rather than single crystal
      samples are used for avoiding the strong electrically self-polarized effect in
      single crystals, and various parallel experiments on excluding the thermally
      excited current contributions are performed. The temperature-dependent electric
      polarization flop as a major character is identified for different measuring
      paths. The magneto-current measurements indicate that the electric polarization
      in the low temperature magnetic phase region has different origin from that in
      the high temperature magnetic phase. It is suggested that the electric
      polarization does have multiple components which align along different
      orientations, including the Mn3+-Mn4+-Mn3+ exchange striction induced
      polarization PMM, the Tm3+-Mn4+-Tm3+ exchange striction induced polarization PTM,
      and the low temperature polarization PLT probably associated with the Tm3+
      commensurate phase. The observed electric polarization flop can be reasonably
      explained by the ferrielectric model proposed earlier for DyMn2O5, where PMM and
      PTM are the two antiparallel components both along the b-axis and PLT may align
      along the a-axis. Finally, several issues on the unusual temperature dependence
      of ferroelectric polarizations are discussed.

PMID- 27713483
TI  - The smallest chimera state for coupled pendula.
AB  - Chimera states in the systems of coupled identical oscillators are spatiotemporal
      patterns in which different groups of oscillators can exhibit coexisting
      synchronous and incoherent behaviors despite homogeneous coupling. Although these
      states are typically observed in large ensembles of oscillators, recently it has
      been suggested that chimera states may occur in the systems with small numbers of
      oscillators. Here, considering three coupled pendula showing chaotic behavior, we
      find the pattern of the smallest chimera state, which is characterized by the
      coexistence of two synchronized and one incoherent oscillator. We show that this
      chimera state can be observed in simple experiments with mechanical oscillators,
      which are controlled by elementary dynamical equations derived from Newton's
      laws. Our finding suggests that chimera states are observable in small networks
      relevant to various real-world systems.

PMID- 27713485
TI  - Targeting Stress Pathophysiology to Improve Alcoholism Relapse Outcomes.

PMID- 27713484
TI  - A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with
      Risk of Lung Cancer.
AB  - Lung cancer etiology is multifactorial, and growing evidence has indicated that
      long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. We
      performed a large-scale meta-analysis of 690,564 SNPs in 15,531 autosomal lncRNAs
      by using datasets from six previously published genome-wide association studies
      (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL)
      consortium in populations of European ancestry. Previously unreported significant
      SNPs (P value < 1 * 10-7) were further validated in two additional independent
      lung cancer GWAS datasets from Harvard University and deCODE. In the final meta
      analysis of all eight GWAS datasets with 17,153 cases and 239,337 controls, a
      novel risk SNP rs114020893 in the lncRNA NEXN-AS1 region at 1p31.1 remained
      statistically significant (odds ratio = 1.17; 95% confidence interval = 1.11
      1.24; P = 8.31 * 10-9). In further in silico analysis, rs114020893 was predicted
      to change the secondary structure of the lncRNA. Our finding indicates that SNP
      rs114020893 of NEXN-AS1 at 1p31.1 may contribute to lung cancer susceptibility.

PMID- 27713488
TI  - Traumatic brain injury: Carbon monoxide - a potential therapy for traumatic brain
      injury?

PMID- 27713486
TI  - The phasor-FLIM fingerprints reveal shifts from OXPHOS to enhanced glycolysis in
      Huntington Disease.
AB  - Huntington disease (HD) is an autosomal neurodegenerative disorder caused by the
      expansion of Polyglutamine (polyQ) in exon 1 of the Huntingtin protein. Glutamine
      repeats below 36 are considered normal while repeats above 40 lead to HD.
      Impairment in energy metabolism is a common trend in Huntington pathogenesis;
      however, this effect is not fully understood. Here, we used the phasor approach
      and Fluorescence Lifetime Imaging Microscopy (FLIM) to measure changes between
      free and bound fractions of NADH as a indirect measure of metabolic alteration in
      living cells. Using Phasor-FLIM, pixel maps of metabolic alteration in HEK293
      cell lines and in transgenic Drosophila expressing expanded and unexpanded polyQ
      HTT exon1 in the eye disc were developed. We found a significant shift towards
      increased free NADH, indicating an increased glycolytic state for cells and
      tissues expressing the expanded polyQ compared to unexpanded control. In the
      nucleus, a further lifetime shift occurs towards higher free NADH suggesting a
      possible synergism between metabolic dysfunction and transcriptional regulation.
      Our results indicate that metabolic dysfunction in HD shifts to increased
      glycolysis leading to oxidative stress and cell death. This powerful label free
      method can be used to screen native HD tissue samples and for potential drug
      screening.

PMID- 27713487
TI  - Alzheimer disease: Preclinical Alzheimer disease - the new frontier.

PMID- 27713490
TI  - Headache: Headache disorders may be a harbinger of hypothyroidism.

PMID- 27713489
TI  - In the news: Treatment guidelines and positive trials at ECTRIMS.

PMID- 27713491
TI  - Motor neuron disease: Smoking adversely affects survival in patients with
      amyotrophic lateral sclerosis.

PMID- 27713492
TI  - Alzheimer disease: Cerebral blood flow could be a marker for Alzheimer disease
      severity.

PMID- 27713494
TI  - Locating the depth of magma supply for volcanic eruptions, insights from Mt.
      Cameroon.
AB  - Mt. Cameroon is one of the most active volcanoes in Africa and poses a possible
      threat to about half a million people in the area, yet knowledge of the volcano's
      underlying magma supply system is sparse. To characterize Mt. Cameroon's magma
      plumbing system, we employed mineral-melt equilibrium thermobarometry on the
      products of the volcano's two most recent eruptions of 1999 and 2000. Our results
      suggest pre-eruptive magma storage between 20 and 39 km beneath Mt. Cameroon,
      which corresponds to the Moho level and below. Additionally, the 1999 eruption
      products reveal several shallow magma pockets between 3 and 12 km depth, which
      are not detected in the 2000 lavas. This implies that small-volume magma batches
      actively migrate through the plumbing system during repose intervals. Evolving
      and migrating magma parcels potentially cause temporary unrest and short-lived
      explosive outbursts, and may be remobilized during major eruptions that are fed
      from sub-Moho magma reservoirs.

PMID- 27713493
TI  - SDF-1alpha-induced dual pairs of E-selectin/ligand mediate endothelial progenitor
      cell homing to critical ischemia.
AB  - Homing of endothelial progenitor cells (EPC) to the ischemic tissues is a key
      event in neovascularization and tissue regeneration. In response to ischemic
      insult, injured tissues secrete several chemo-cytokines, including stromal cell
      derived factor-1alpha (SDF-1alpha), which triggers mobilization and homing of
      bone marrow-derived EPC (BMD-EPC). We previously reported that SDF-1alpha-induced
      EPC homing is mediated by a panel of adhesion molecules highly or selectively
      expressed on the activated endothelium in ischemic tissues, including E-selectin.
      Elevated E-selectin on wound vasculature serve as docking sites for circulating
      EPC, which express counterpart E-selectin ligands. Here, we show that SDF-1alpha
      presented in wound tissue and released into circulation can act both locally and
      remotely to induce ischemic tissue endothelium and BMD-EPC to express both E
      selectin and its ligands. By performing BM transplantation using E-selectin-/-
      and E-selectin+/+ mice as the donors and recipients respectively, we demonstrate
      that upregulated dual E-selectin/ligand pairs reciprocally expressed on ischemic
      tissue endothelium and BMD-EPC act as double-locks to secure targeted EPC-
      endothelium interactions by which to facilitate EPC homing and promote
      neovascularization and tissue repair. These findings describe a novel mechanism
      for BMD-EPC homing and indicate that dual E-selectin/ligand pairs may be
      effective targets/tools for therapeutic neovascularization and targeted cell
      delivery.

PMID- 27713496
TI  - Accurate modeling of high-repetition rate ultrashort pulse amplification in
      optical fibers.
AB  - A numerical model for amplification of ultrashort pulses with high repetition
      rates in fiber amplifiers is presented. The pulse propagation is modeled by
      jointly solving the steady-state rate equations and the generalized nonlinear
      Schrodinger equation, which allows accurate treatment of nonlinear and dispersive
      effects whilst considering arbitrary spatial and spectral gain dependencies.
      Comparison of data acquired by using the developed model and experimental results
      prove to be in good agreement.

PMID- 27713495
TI  - Allosteric regulation in NMDA receptors revealed by the genetically encoded photo
      cross-linkers.
AB  - Allostery is essential to neuronal receptor function, but its transient nature
      poses a challenge for characterization. The N-terminal domains (NTDs) distinct
      from ligand binding domains are a major locus for allosteric regulation of NMDA
      receptors (NMDARs), where different modulatory binding sites have been observed.
      The inhibitor ifenprodil, and related phenylethanoamine compounds specifically
      targeting GluN1/GluN2B NMDARs have neuroprotective activity. However, whether
      they use differential structural pathways than the endogenous inhibitor Zn2+ for
      regulation is unknown. We applied genetically encoded unnatural amino acids
      (Uaas) and monitored the functional changes in living cells with photo-cross
      linkers specifically incorporated at the ifenprodil binding interface between
      GluN1 and GluN2B subunits. We report constraining the NTD domain movement, by a
      light induced crosslinking bond that introduces minimal perturbation to the
      ligand binding, specifically impedes the transduction of ifenprodil but not Zn2+
      inhibition. Subtle distance changes reveal interfacial flexibility and NTD
      rearrangements in the presence of modulators. Our results present a much richer
      dynamic picture of allostery than conventional approaches targeting the same
      interface, and highlight key residues that determine functional and subtype
      specificity of NMDARs. The light-sensitive mutant neuronal receptors provide
      complementary tools to the photo-switchable ligands for opto-neuropharmacology.

PMID- 27713497
TI  - Erratum: Insight into the template effect of vesicles on the laccase-catalyzed
      oligomerization of N-phenyl-1,4-phenylenediamine from Raman spectroscopy and
      cyclic voltammetry measurements.

PMID- 27713498
TI  - Prognostic Value of Reverse Dipper Blood Pressure Pattern in Chronic Kidney
      Disease Patients not Undergoing Dialysis: Prospective Cohort Study.
AB  - The "reverse dipping" blood pressure (BP) pattern has been studied among the
      general population and in individuals suffering from hypertension. However, the
      prognosis of this pattern in chronic kidney disease (CKD) patients is not known.
      We monitored BP throughout the day and followed health outcomes in 588 CKD
      patients admitted to our hospital. Time to all-cause mortality, cardiovascular
      mortality, renal events and cardiovascular events was recorded. Multivariate
      adjusted Cox regression analyses were carried out to detect the prognostic value
      of a reverse dipping BP pattern. Prevalence of a "dipper", "non-dipper" and
      "reverse dippers" was 34.69%, 43.54% and 18.03%, respectively. Patients with a
      reverse dipping pattern had a higher prevalence of total mortality,
      cardiovascular mortality, renal events and cardiovascular events than patients
      with a dipping pattern (P < 0.025). Multivariate-adjusted Cox regression analyses
      showed that reverse dippers (versus dippers) were associated with a higher risk
      of total mortality (hazard ratio [HR], 5.08; 95% confidence interval [CI],
      1.79~14.47), cardiovascular mortality (4.17; 1.25~13.88), renal events (3.00;
      1.59~5.65) and cardiovascular events (4.12; 1.78~9.51) even after adjustment by
      24-h systolic BP. These data suggest that a reverse dipping BP pattern,
      independent of 24-h levels of systolic BP, has prognostic value in CKD patients
      not undergoing dialysis.

PMID- 27713500
TI  - Genome Sequencing of the Pyruvate-producing Strain Candida glabrata CCTCC M202019
      and Genomic Comparison with Strain CBS138.
AB  - Candida glabrata CCTCC M202019 as an industrial yeast strain that is widely used
      to produce alpha-oxocarboxylic acid. Strain M202019 has been proven to have a
      higher pyruvate-producing capacity than the reference strain CBS138. To
      characterize the genotype of the M202019 strain, we generated a draft sequence of
      its genome, which has a size of 12.1 Mbp and a GC content of 38.47%. Evidence
      accumulated during genome annotation suggests that strain M202019 has strong
      capacities for glucose transport and pyruvate biosynthesis, defects in pyruvate
      catabolism, as well as variations in genes involved in nutrient and dicarboxylic
      acid transport, oxidative phosphorylation, and other relevant aspects of carbon
      metabolism, which might promote pyruvate accumulation. In addition to differences
      in its central carbon metabolism, a genomic analysis revealed genetic differences
      in adhesion metabolism. Forty-nine adhesin-like proteins of strain M202019 were
      identified classified into seven subfamilies. Decreased amounts of adhesive
      proteins, and deletions or changes of low-complexity repeats and functional
      domains might lead to lower adhesion and reduced pathogenicity. Further virulence
      experiments validated the biological safety of strain M202019. Analysis of the C.
      glabrata CCTCC M202019 genome sequence provides useful insights into its genetic
      context, physical characteristics, and potential metabolic capacity.

PMID- 27713499
TI  - Disruption of ArhGAP15 results in hyperactive Rac1, affects the architecture and
      function of hippocampal inhibitory neurons and causes cognitive deficits.
AB  - During brain development, the small GTPases Rac1/Rac3 play key roles in neuronal
      migration, neuritogenesis, synaptic formation and plasticity, via control of
      actin cytoskeleton dynamic. Their activity is positively and negatively regulated
      by GEFs and GAPs molecules, respectively. However their in vivo roles are poorly
      known. The ArhGAP15 gene, coding for a Rac-specific GAP protein, is expressed in
      both excitatory and inhibitory neurons of the adult hippocampus, and its loss
      results in the hyperactivation of Rac1/Rac3. In the CA3 and dentate gyrus (DG)
      regions of the ArhGAP15 mutant hippocampus the CR+, PV+ and SST+ inhibitory
      neurons are reduced in number, due to reduced efficiency and directionality of
      their migration, while pyramidal neurons are unaffected. Loss of ArhGAP15 alters
      neuritogenesis and the balance between excitatory and inhibitory synapses, with a
      net functional result consisting in increased spike frequency and bursts,
      accompanied by poor synchronization. Thus, the loss of ArhGAP15 mainly impacts on
      interneuron-dependent inhibition. Adult ArhGAP15-/- mice showed defective
      hippocampus-dependent functions such as working and associative memories. These
      findings indicate that a normal architecture and function of hippocampal
      inhibitory neurons is essential for higher hippocampal functions, and is
      exquisitely sensitive to ArhGAP15-dependent modulation of Rac1/Rac3.

PMID- 27713501
TI  - In vivo analysis of internal ribosome entry at the Hairless locus by genome
      engineering in Drosophila.
AB  - Cell communication in metazoans requires the highly conserved Notch signaling
      pathway, which is subjected to strict regulation of both activation and
      silencing. In Drosophila melanogaster, silencing involves the assembly of a
      repressor complex by Hairless (H) on Notch target gene promoters. We previously
      found an in-frame internal ribosome entry site in the full length H transcript
      resulting in two H protein isoforms (Hp120 and Hp150). Hence, H may repress Notch
      signalling activity in situations where cap-dependent translation is inhibited.
      Here we demonstrate the in vivo importance of both H isoforms for proper fly
      development. To this end, we replaced the endogenous H locus by constructs
      specifically affecting translation of either Hp150 or Hp120 isoforms using genome
      engineering. Our findings indicate the functional relevance of both H proteins.
      Based on bristle phenotypes, the predominant isoform Hp150 appears to be of
      particular importance. In contrast, growth regulation and venation of the wing
      require the concomitant activity of both isoforms. Finally, the IRES dependent
      production of Hp120 during mitosis was verified in vivo. Together our data
      confirm IRES mediated translation of H protein in vivo, supporting strict
      regulation of Notch in different cellular settings.

PMID- 27713502
TI  - Nutrient reduction induced stringent responses promote bacterial quorum-sensing
      divergence for population fitness.
AB  - Bacteria use a cell-cell communication system termed quorum-sensing (QS) to
      adjust population size by coordinating the costly but beneficial cooperative
      behaviors. It has long been suggested that bacterial social conflict for
      expensive extracellular products may drive QS divergence and cause the "tragedy
      of the commons". However, the underlying molecular mechanism of social divergence
      and its evolutionary consequences for the bacterial ecology still remain largely
      unknown. By using the model bacterium Pseudomonas aeruginosa PAO1, here we show
      that nutrient reduction can promote QS divergence for population fitness during
      evolution but requiring adequate cell density. Mechanically, decreased nutrient
      supplies can induce RpoS-directed stringent response and enhance the selection
      pressure on lasR gene, and lasR mutants are evolved in association with the DNA
      mismatch repair "switch-off". The lasR mutants have higher relative fitness than
      QS-intact individuals due to their energy-saving characteristic under nutrient
      decreased condition. Furthermore an optimal incorporation of lasR mutants is
      capable of maximizing the fitness of entire population during in vitro culture
      and the colonization in mouse lung. Consequently, rather than worsen the
      population health, QS-coordinated social divergence is an elaborate evolutionary
      strategy that renders the entire bacterial population more fit in tough times.

PMID- 27713503
TI  - Left Atrial trajectory impairment in Hypertrophic Cardiomyopathy disclosed by
      Geometric Morphometrics and Parallel Transport.
AB  - The analysis of full Left Atrium (LA) deformation and whole LA deformational
      trajectory in time has been poorly investigated and, to the best of our
      knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy.
      Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and
      46 healthy subjects, investigated them by three-dimensional Speckle Tracking
      Echocardiography, and studied the derived landmark clouds via Geometric
      Morphometrics with Parallel Transport. Trajectory shape and trajectory size were
      different in Controls versus HCM and their classification powers had high AUC
      (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two
      trajectories were much different at the transition between LA conduit and booster
      pump functions. Full shape and deformation analyses with trajectory analysis
      enabled a straightforward perception of pathophysiological consequences of HCM
      condition on LA functioning. It might be worthwhile to apply these techniques to
      look for novel pathophysiological approaches that may better define atrio
      ventricular interaction.

PMID- 27713504
TI  - Metabolomics of aging assessed in individual parasitoid wasps.
AB  - Metabolomics studies of low-biomass organisms, such as small insects, have
      previously relied on the pooling of biological samples to overcome detection
      limits, particularly using NMR. We show that the differentiation of metabolite
      profiles of individual 1 mg parasitoid wasps of different ages is possible when
      using a modified sample preparation and a combination of untargeted NMR and LC-MS
      based metabolomics. Changes were observed between newly emerged and older wasps
      in glycerolipids, amino acids and circulatory sugars. This advance in chemical
      profiling has important implications for the study of the behaviour and ecology
      of parasitoids and many other species of small organisms because predictions and
      observations are typically made at the level of the individual. Thus, the
      metabolomic state of low-biomass individuals can now be related to their
      behaviour and ecological performance. We discuss specifically the utility of age
      related metabolomic profiling but our new approach can be applied to a wide range
      of biological research.

PMID- 27713505
TI  - Zika virus infection during the period of maximal brain growth causes
      microcephaly and corticospinal neuron apoptosis in wild type mice.
AB  - Zika virus (ZIKV) infection in pregnant women has been established as a cause of
      microcephaly in newborns. Here we test the hypothesis that neurodevelopmental
      stages when the brain is undergoing rapid growth are particularly vulnerable to
      the effects of ZIKV infection. We injected ZIKV intracranially into wild type
      C57BL/6 mice at two different time points: early postnatal development, when the
      brain is growing at its maximal rate, and at weaning, when the brain has largely
      reached adult size. Both time points showed widespread immunoreactivity for ZIKV
      and cleaved caspase 3 (CC3, a marker of apoptosis) throughout the brain. However,
      in early postnatal ZIKV injected mice, some brain areas and cell types display
      particularly large increases in apoptosis that we did not observe in older
      animals. Corticospinal pyramidal neurons, a cell type implicated in human
      microcephaly associated with ZIKV infection, are an example of one such cell
      type. Proliferating cells in the ventricular zone stem cell compartment are also
      depleted. These findings are consistent with the hypothesis that periods of rapid
      brain growth are especially susceptible to neurodevelopmental effects of ZIKV
      infection, and establish a valuable model to investigate mechanisms underlying
      neurodevelopmental effects of ZIKV infection and explore candidate therapeutics.

PMID- 27713506
TI  - PAK1 confers chemoresistance and poor outcome in non-small cell lung cancer via
      beta-catenin-mediated stemness.
AB  - PAK1 confers resistance to the estrogen antagonist tamoxifen in breast cancer.
      However, a role for PAK1 remains to be elucidated for chemoresistance and
      prognosis in non-small cell lung cancer (NSCLC). We provide evidence that PAK1
      confers cisplatin resistance by increasing beta-catenin expression through
      ERK/GSK3beta signaling. The increased beta-catenin expression promotes sphere
      cell formation and expression of stemness markers and this beta-catenin-induced
      stemness is responsible for PAK1-mediated cisplatin resistance. We enrolled 87
      NSCLC patients who had received cisplatin-based chemotherapy to confirm the
      association between PAK1 expression and response to chemotherapy and outcomes.
      PAK1 expression, evaluated by immunohistochemistry, was positively correlated
      with pERK and beta-catenin expression in lung tumors. Patients with high-PAK1,
      high-pERK, and high-nuclear beta-catenin tumors more frequently showed an
      unfavorable response to cisplatin-based chemotherapy when compared to their
      counterparts. Kaplan-Meier and Cox regression analysis also indicated a poorer
      overall survival (OS) and relapse free survival (RFS) in patients with high-PAK1,
      high-pERK, and high-nuclear beta-catenin tumors. In conclusion, PAK1 confers
      cisplatin resistance in NSCLC via beta-catenin-mediated stemness. Therefore, we
      suggest that clinical use of a combination of the MEK/ERK inhibitor AZD6244 and
      cisplatin might improve sensitivity to cisplatin-based chemotherapy and outcomes
      in NSCLC patients who harbor high-PAK1-expressing tumors.

PMID- 27713507
TI  - Versatile members of the DNAJ family show Hsp70 dependent anti-aggregation
      activity on RING1 mutant parkin C289G.
AB  - Parkinson's disease is one of the most common neurodegenerative disorders and
      several mutations in different genes have been identified to contribute to the
      disease. A loss of function parkin RING1 domain mutant (C289G) is associated with
      autosomal-recessive juvenile-onset Parkinsonism (AR-JP) and displays altered
      solubility and sequesters into aggregates. Single overexpression of almost each
      individual member of the Hsp40 (DNAJ) family of chaperones efficiently reduces
      parkin C289G aggregation and requires interaction with and activity of
      endogenously expressed Hsp70 s. For DNAJB6 and DNAJB8, potent suppressors of
      aggregation of polyglutamine proteins for which they rely mainly on an S/T-rich
      region, it was found that the S/T-rich region was dispensable for suppression of
      parkin C289G aggregation. Our data implies that different disease-causing
      proteins pose different challenges to the protein homeostasis system and that
      DNAJB6 and DNAJB8 are highly versatile members of the DNAJ protein family with
      multiple partially non-overlapping modes of action with respect to handling
      disease-causing proteins, making them interesting potential therapeutic targets.

PMID- 27713509
TI  - Islanding the power grid on the transmission level: less connections for more
      security.
AB  - Islanding is known as a management procedure of the power system that is
      implemented at the distribution level to preserve sensible loads from outages and
      to guarantee the continuity in electricity supply, when a high amount of
      distributed generation occurs. In this paper we study islanding on the level of
      the transmission grid and shall show that it is a suitable measure to enhance
      energy security and grid resilience. We consider the German and Italian
      transmission grids. We remove links either randomly to mimic random failure
      events, or according to a topological characteristic, their so-called betweenness
      centrality, to mimic an intentional attack and test whether the resulting
      fragments are self-sustainable. We test this option via the tool of optimized DC
      power flow equations. When transmission lines are removed according to their
      betweenness centrality, the resulting islands have a higher chance of being
      dynamically self-sustainable than for a random removal. Less connections may even
      increase the grid's stability. These facts should be taken into account in the
      design of future power grids.

PMID- 27713508
TI  - Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse
      Forebrain Causes Dendritic Malformation via beta-catenin.
AB  - Breast carcinoma amplified sequence 2 (BCAS2) is a core component of the hPrP19
      complex that controls RNA splicing. Here, we performed an exon array assay and
      showed that beta-catenin is a target of BCAS2 splicing regulation. The regulation
      of dendrite growth and morphology by beta-catenin is well documented. Therefore,
      we generated conditional knockout (cKO) mice to eliminate the BCAS2 expression in
      the forebrain to investigate the role of BCAS2 in dendrite growth. BCAS2 cKO mice
      showed a microcephaly-like phenotype with a reduced volume in the dentate gyrus
      (DG) and low levels of learning and memory, as evaluated using Morris water maze
      analysis and passive avoidance, respectively. Golgi staining revealed shorter
      dendrites, less dendritic complexity and decreased spine density in the DG of
      BCAS2 cKO mice. Moreover, the cKO mice displayed a short dendrite length in
      newborn neurons labeled by DCX, a marker of immature neurons, and BrdU
      incorporation. To further examine the mechanism underlying BCAS2-mediated
      dendritic malformation, we overexpressed beta-catenin in BCAS2-depleted primary
      neurons and found that the dendritic growth was restored. In summary, BCAS2 is an
      upstream regulator of beta-catenin gene expression and plays a role in dendrite
      growth at least partly through beta-catenin.

PMID- 27713510
TI  - Hierarchically-structured silver nanoflowers for highly conductive metallic inks
      with dramatically reduced filler concentration.
AB  - Silver has long been employed as an electrically conductive component, and
      morphology-dependent properties have been actively investigated. Here we present
      a novel scalable synthesis method of flower-shaped silver nanoparticles (silver
      nanoflowers, Ag NFs). The preferential affinity of citrate molecules on (111)
      surface of silver enabled spontaneous anisotropic growth of Ag NFs (bud size:
      250~580 nm, single crystalline petal thickness: 9~22 nm) with high
      reproducibility and a high yield of >99.5%. The unique hierarchical structure
      resulted in coalescence of petals over 80~120  degrees C which was practically
      employed in conductive inks to construct percolation pathways among Ag NFs. The
      ink with only 3 wt% of Ag NFs provided two orders of magnitude greater
      conductivity (1.008 * 105 Scm-1), at a low curing temperature of 120  degrees C,
      compared with the silver nanoparticle ink with a much higher silver concentration
      (50 wt%). This extraordinary property may provide an excellent opportunity for Ag
      NFs for practical applications in printable and flexible electronics.

PMID- 27713511
TI  - Cell surface GRP78 as a biomarker and target for suppressing glioma cells.
AB  - High-grade glioma is a highly malignant and metastatic brain cancer, resistant to
      many existing anticancer treatments. In such glioma cancer cells, the glucose
      regulated protein 78 kDa (GRP78) is particularly highly up-regulated. Former
      studies have thus targeted mutation-free GRP78 not only to detect glioma cancer
      cells specifically but also to enhance cytotoxic effect. We focus on cell surface
      expressed GRP78 as a target for suppressing high-grade glioma cell lines.
      Glioblastoma multiforme (GBM) cell line, highly malignant glioma cells, was first
      injected into 5-week-old athymic mice to confirm and compare GRP78 expression in
      vivo in xenografted and normal brain tissue. Immunofluorescence and
      immunoblotting were utilized to detect surface-localized GRP78 in diverse high
      grade glioma cell lines. By treating glioma cell lines with the polyclonal N-20
      antibody against surface-localized GRP78, we subsequently studied the
      significance of surface GRP78 to the survival and growth of the glioma cell
      lines. We found that inhibiting the function of surface GRP78 suppressed cancer
      cell survival and growth proving that the surface-expressed GRP78 is a vital
      receptor involved in the proliferation of high-grade glioma. Our findings provide
      opportunities to target surface GRP78 as a biomarker for high-grade glioma and to
      develop effective cell-specific anticancer therapy.

PMID- 27713512
TI  - Marangoni effect visualized in two-dimensions Optical tweezers for gas bubbles.
AB  - In the report we demonstrate how, using laser light, effectively trap gas bubbles
      and transport them through a liquid phase to a desired destination by shifting
      the laser beam position. The physics underlying the effect is complex but quite
      general as it comes from the limited to two-dimension, well-known, Marangoni
      effect. The experimental microscope-based system consists of a thin layer of
      liquid placed between two glass plates containing a dye dissolved in a solvent
      and a laser light beam that is strongly absorbed by the dye. This point-like heat
      source locally changes surface tension of nearby liquid-air interface. Because of
      temperature gradients a photo-triggered Marangoni flows are induced leading to
      self-amplification of the effect and formation of large-scale whirls. The
      interface is bending toward beam position allowing formation of a gas bubble upon
      suitable beam steering. Using various techniques (employing luminescent particles
      or liquid crystals), we visualize liquid flows propelled by the tangential to
      interface forces. This helped us to understand the physics of the phenomenon and
      analyze accompanying effects leading to gas bubble trapping. The manipulation of
      sessile droplets moving on the glass surface induced via controlled with laser
      light interface bending (i.e. "droplet catapult") is demonstrated as well.

PMID- 27713513
TI  - Computational identification of putative lincRNAs in mouse embryonic stem cell.
AB  - As the regulatory factors, lncRNAs play critical roles in embryonic stem cells.
      And lincRNAs are most widely studied lncRNAs, however, there might still might
      exist a large member of uncovered lncRNAs. In this study, we constructed the de
      novo assembly of transcriptome to detect 6,701 putative long intergenic non
      coding transcripts (lincRNAs) expressed in mouse embryonic stem cells (ESCs),
      which might be incomplete with the lack coverage of 5' ends assessed by CAGE
      peaks. Comparing the TSS proximal regions between the known lincRNAs and their
      closet protein coding transcripts, our results revealed that the lincRNA TSS
      proximal regions are associated with the characteristic genomic and epigenetic
      features. Subsequently, 1,293 lincRNAs were corrected at their 5' ends using the
      putative lincRNA TSS regions predicted by the TSS proximal region prediction
      model based on genomic and epigenetic features. Finally, 43 putative lincRNAs
      were annotated by Gene Ontology terms. In conclusion, this work provides a novel
      catalog of mouse ESCs-expressed lincRNAs with the relatively complete transcript
      length, which might be useful for the investigation of transcriptional and post
      transcriptional regulation of lincRNA in mouse ESCs and even mammalian
      development.

PMID- 27713514
TI  - Anti-neuropathic effects of Rosmarinus officinalis L. terpenoid fraction:
      relevance of nicotinic receptors.
AB  - Traditional uses and current results highlight the neuroprotective properties of
      Rosmarinus officinalis L. The compelling need for novel strategies able to
      relieve neuropathic pain encouraged us to analyze different rosemary leaf
      extracts in rats following chronic constriction injury (CCI) of sciatic nerve.
      Ethanol, acetone, and the innovative ultrasound-hexane extractive methods were
      used to obtain: EE, AE, and for hexane extracts UREprel and URE. Extracts were
      characterized in terms of typical constituents and repeatedly administered to CCI
      rats (13-days treatment, from the day of surgery). URE showed the best efficacy
      and potency in reducing hypersensitivity to noxious- and non-noxious stimuli and
      spontaneous pain. URE contained the higher quantity of the terpenoid carnosic
      acid (CA) and its efficacy was compared to pure CA. Histological analysis of the
      sciatic nerve revealed that URE prevented axon and myelin derangement, edema and
      inflammatory infiltrate. In the dorsal horn of the spinal cord, URE did not
      reduce astrocyte activation. Both the pain reliever and the neuroconservative
      effects of URE were significantly prevented by the nicotinic receptor (nAChR)
      antagonist mecamylamine. In conclusion, the hexane-ultrasound rosemary extract is
      able to reduce neuropathic hypersensitivity and protect nervous tissues.
      Effectiveness is mainly related to the terpenoid fraction by mechanisms involving
      nAChRs.

PMID- 27713515
TI  - The influence of single nucleotide polymorphisms on the association between
      dietary acrylamide intake and endometrial cancer risk.
AB  - It is unclear whether the association between dietary acrylamide intake and
      endometrial cancer risk as observed in some epidemiological studies reflects a
      causal relationship. We aimed at clarifying the causality by analyzing acrylamide
      gene interactions for endometrial cancer risk. 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 selected for a case cohort analysis approach.
      Acrylamide intake of subcohort members and endometrial cancer cases (n = 315) was
      assessed with a food frequency questionnaire. Single nucleotide polymorphisms
      (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress
      and DNA repair were assessed through a MassARRAY iPLEX Platform. Interaction
      between acrylamide and SNPs was assessed with Cox proportional hazards analysis,
      based on 11.3 years of follow-up. Among the results for 57 SNPs and 2 gene
      deletions, there were no statistically significant interactions after adjustment
      for multiple testing. However, there were nominally statistically significant
      interactions for SNPs in acrylamide-metabolizing enzymes: CYP2E1 (rs915906 and
      rs2480258) and the deletions of GSTM1 and GSTT1. Although in need of
      confirmation, the interactions between acrylamide intake and CYP2E1 SNPs
      contribute to the evidence for a causal relationship between acrylamide and
      endometrial cancer risk.

PMID- 27713516
TI  - How Humans Solve Complex Problems: The Case of the Knapsack Problem.
AB  - Life presents us with problems of varying complexity. Yet, complexity is not
      accounted for in theories of human decision-making. Here we study instances of
      the knapsack problem, a discrete optimisation problem commonly encountered at all
      levels of cognition, from attention gating to intellectual discovery. Complexity
      of this problem is well understood from the perspective of a mechanical device
      like a computer. We show experimentally that human performance too decreased with
      complexity as defined in computer science. Defying traditional economic
      principles, participants spent effort way beyond the point where marginal gain
      was positive, and economic performance increased with instance difficulty. Human
      attempts at solving the instances exhibited commonalities with algorithms
      developed for computers, although biological resource constraints-limited working
      and episodic memories-had noticeable impact. Consistent with the very nature of
      the knapsack problem, only a minority of participants found the solution-often
      quickly-but the ones who did appeared not to realise. Substantial heterogeneity
      emerged, suggesting why prizes and patents, schemes that incentivise intellectual
      discovery but discourage information sharing, have been found to be less
      effective than mechanisms that reveal private information, such as markets.

PMID- 27713517
TI  - Implementation of Arithmetic and Nonarithmetic Functions on a Label-free and DNA
      based Platform.
AB  - A series of complex logic gates were constructed based on graphene oxide and DNA
      templated silver nanoclusters to perform both arithmetic and nonarithmetic
      functions. For the purpose of satisfying the requirements of progressive
      computational complexity and cost-effectiveness, a label-free and universal
      platform was developed by integration of various functions, including half adder,
      half subtractor, multiplexer and demultiplexer. The label-free system avoided
      laborious modification of biomolecules. The designed DNA-based logic gates can be
      implemented with readout of near-infrared fluorescence, and exhibit great
      potential applications in the field of bioimaging as well as disease diagnosis.

PMID- 27713518
TI  - Large gap Quantum Spin Hall Insulators of Hexagonal III-Bi monolayer.
AB  - In the present work, we demonstrate that both GaBi3 and InBi3 monolayers are
      Quantum Spin Hall insulators. Here, the electronic band structures and edge
      states of the two novel monolayers are systematically investigated by first
      principle calculation. Our analysis of the band inversion and Z2 number
      demonstrate that both GaBi3 and InBi3 are promising 2D TIs with large gaps of
      283meV and 247meV, respectively. Taking GaBi3 as example, it is illustrated that
      the edge states are impacted by SOC and finite size effect. In addition, it is
      found that the compression and tension totally affect differently on the edge
      states. Finally, the electron velocity is studied in detail, which is highly
      important in the manufacturing of spintronics device.

PMID- 27713519
TI  - Use of aerosol route to fabricate positively charged Au/Fe3O4 Janus nanoparticles
      as multifunctional nanoplatforms.
AB  - Gold (Au)-decorated iron oxide (Fe3O4), Au/Fe3O4, Janus nanoparticles were
      fabricated via the continuous route for aerosol Au incorporation with Fe3O4
      domains synthesized in an aqueous medium as multifunctional nanoplatforms. The
      fabricated nanoparticles were subsequently exposed to 185-nm UV light to generate
      positive charges on Au surfaces, and their activities were tested in computed
      tomography (CT) and magnetic resonance (MR) imaging, gene-delivery and
      photothermal therapy. No additional polymeric coatings of the Janus particles
      also had a unique ability to suppress inflammatory responses in macrophages
      challenged with lipopolysaccharide, which may be due to the absence of amine
      groups.

PMID- 27713520
TI  - Identifying molecular signatures of hypoxia adaptation from sex chromosomes: A
      case for Tibetan Mastiff based on analyses of X chromosome.
AB  - Genome-wide studies on high-altitude adaptation have received increased attention
      as a classical case of organismal evolution under extreme environment. However,
      the current genetic understanding of high-altitude adaptation emanated mainly
      from autosomal analyses. Only a few earlier genomic studies paid attention to the
      allosome. In this study, we performed an intensive scan of the X chromosome of
      public genomic data generated from Tibetan Mastiff (TM) and five other dog
      populations for indications of high-altitude adaptation. We identified five genes
      showing signatures of selection on the X chromosome. Notable among these genes
      was angiomotin (AMOT), which is related to the process of angiogenesis. We
      sampled additional 11 dog populations (175 individuals in total) at continuous
      altitudes in China from 300 to 4,000 meters to validate and test the association
      between the haplotype frequency of AMOT gene and altitude adaptation. The results
      suggest that AMOT gene may be a notable candidate gene for the adaptation of TM
      to high-altitude hypoxic conditions. Our study shows that X chromosome deserves
      consideration in future studies of adaptive evolution.

PMID- 27713521
TI  - Transcriptome Comparison Analysis of Ostrinia furnacalis in Four Developmental
      Stages.
AB  - The Asian corn borer, Ostrinia furnacalis, is one of the most destructive pests
      of maize and causes huge losses in maize yield each year. In order to
      characterize the different developmental stages, a high-throughput sequencing
      platform was employed to perform de novo transcriptome assembly and gene
      expression analysis for the egg, larva, pupa and adult stages. Approximately 185
      million reads were obtained, trimmed, and assembled into 42,638 unigenes with an
      average length of 801.94 bp and an N50 length of 1,152 bp. These unigene
      sequences were annotated and classified by performing Gene Ontology (GO), Cluster
      of Orthologous Groups (KOG) and Kyoto Encyclopedia of Genes and Genomes (KEGG)
      functional classifications. Comparison of the gene expression profiles of the two
      transitional stages revealed dramatic differences. Some differentially expressed
      genes are associated with digestion, cuticularization olfactory recognition and
      wing formation as well as growth and development. In total, 12 putative insect
      development-related genes were identified. Real-time quantitative PCR (RT-qPCR)
      results and sequencing based on relative expression levels of randomly selected
      genes confirmed these expression patterns. These data represent the most
      comprehensive transcriptomic resource currently available for O. furnacalis and
      will facilitate the study of developmental pathways, cuticularization, wing
      formation and olfactory recognition.

PMID- 27713522
TI  - Ultrafast spin dynamics and switching via spin transfer torque in
      antiferromagnets with weak ferromagnetism.
AB  - The spin-torque driven dynamics of antiferromagnets with Dzyaloshinskii-Moriya
      interaction (DMI) were investigated based on the Landau-Lifshitz-Gilbert
      Slonczewski equation with antiferromagnetic and ferromagnetic order parameters (l
      and m, respectively). We demonstrate that antiferromagnets including DMI can be
      described by a 2-dimensional pendulum model of l. Because m is coupled with l,
      together with DMI and exchange energy, close examination of m provides
      fundamental understanding of its dynamics in linear and nonlinear regimes.
      Furthermore, we discuss magnetization reversal as a function of DMI and
      anisotropy energy induced by a spin current pulse.

PMID- 27713523
TI  - Effects of Melanocortin 3 and 4 Receptor Deficiency on Energy Homeostasis in
      Rats.
AB  - Melanocortin-3 and 4 receptors (MC3R and MC4R) can regulate energy homeostasis,
      but their respective roles especially the functions of MC3R need more
      exploration. Here Mc3r and Mc4r single and double knockout (DKO) rats were
      generated using CRISPR-Cas9 system. Metabolic phenotypes were examined and data
      were compared systematically. Mc3r KO rats displayed hypophagia and decreased
      body weight, while Mc4r KO and DKO exhibited hyperphagia and increased body
      weight. All three mutants showed increased white adipose tissue mass and
      adipocyte size. Interestingly, although Mc3r KO did not show a significant
      elevation in lipids as seen in Mc4r KO, DKO displayed even higher lipid levels
      than Mc4r KO. DKO also showed more severe glucose intolerance and hyperglycaemia
      than Mc4r KO. These data demonstrated MC3R deficiency caused a reduction of food
      intake and body weight, whereas at the same time exhibited additive effects on
      top of MC4R deficiency on lipid and glucose metabolism. This is the first
      phenotypic analysis and systematic comparison of Mc3r KO, Mc4r KO and DKO rats on
      a homogenous genetic background. These mutant rats will be important in defining
      the complicated signalling pathways of MC3R and MC4R. Both Mc4r KO and DKO are
      good models for obesity and diabetes research.

PMID- 27713526
TI  - NO gas sensing kinetics at room temperature under UV light irradiation of In2O3
      nanostructures.
AB  - In2O3 nanostructure sensors were fabricated by arc-discharging a source composed
      of a graphite tube containing indium. The NO gas sensing properties, as well as
      the morphology, structure, and electrical properties, were examined at room
      temperature under UV light illumination. In particular, the response and recovery
      kinetics of the sensor at room temperature under various UV light intensities
      were studied. The maximum response signal was observed at an intermediate UV
      light intensity, which could be corroborated by a nano-size effect based on the
      conduction model of a resistive chemical nano sensor. The mechanism for the
      enhanced adsorption/desorption kinetics for NO in an air environment under UV
      light irradiation is discussed in detail. Furthermore, the general requirements
      of the sensor, including the stability, repeatability, and selectivity, are
      discussed.

PMID- 27713525
TI  - Behaviors of Microcystis aeruginosa cells during floc storage in drinking water
      treatment process.
AB  - This is the first study to systematically investigate the different behaviors of
      Microcystis aeruginosa in the sludges formed by AlCl3, FeCl3, and polymeric
      aluminium ferric chloride (PAFC) coagulants during storage. Results show that the
      viability of Microcystis aeruginosa in PAFC sludge was stronger than that of
      cells in either AlCl3 or FeCl3 sludge after the same storage time, while the
      cells' viability in the latter two systems stayed at almost the same level. In
      AlCl3 and FeCl3 sludges high concentrations of Al and Fe were toxic to
      Microcystis aeruginosa, whereas in PAFC sludge low levels of Al showed little
      toxic effect on Microcystis aeruginosa growth and moderate amounts of Fe were
      beneficial to growth. The lysis of Microcystis aeruginosa in AlCl3 sludge was
      more serious than that in PAFC sludge, for the same storage time. Although the
      cell viability in FeCl3 sludge was low (similar to AlCl3 sludge), the Microcystis
      aeruginosa cells remained basically intact after 10 d storage (similar to PAFC
      sludge). The maintenance of cellular integrity in FeCl3 sludge might be due to
      the large floc size and high density, which had a protective effect for
      Microcystis aeruginosa.

PMID- 27713524
TI  - GhABF2, a bZIP transcription factor, confers drought and salinity tolerance in
      cotton (Gossypium hirsutum L.).
AB  - The bZIP transcription factor (TF) act as an important regulator for the abscisic
      acid (ABA) mediated abiotic stresses signaling pathways in plants. Here, we
      reported the cloning and characterization of GhABF2, encoding for typical cotton
      bZIP TF. Overexpression of GhABF2 significantly improved drought and salt stress
      tolerance both in Arabidopsis and cotton. However, silencing of GhABF2 made
      transgenic cotton sensitive to PEG osmotic and salt stress. Expression of GhABF2
      was induced by drought and ABA treatments but repressed by high salinity.
      Transcriptome analysis indicated that GhABF2 increases drought and salt tolerance
      by regulating genes related to ABA, drought and salt response. The proline
      contents, activity of superoxide dismutase (SOD) and catalase (CAT) were also
      significantly increased in GhABF2-overexpression cottons in comparison to wild
      type after drought and salt treatment. Further, an increase in fiber yield under
      drought and saline-alkali wetland exhibited the important role of GhABF2 in
      enhancing the drought and salt tolerance in transgenic lines. In conclusion,
      manipulation of GhABF2 by biotechnological tools could be a sustainable strategy
      to deploy drought and salt tolerance in cotton.

PMID- 27713527
TI  - Thermal and Thermoelectric Transport in Highly Resistive Single Sb2Se3 Nanowires
      and Nanowire Bundles.
AB  - In this study, we measured the thermal conductivity and Seebeck coefficient of
      single Sb2Se3 nanowires and nanowire bundles with a high resistivity (sigma ~
      4.37 * 10-4 S/m). Microdevices consisting of two adjacent suspended silicon
      nitride membranes were fabricated to measure the thermal transport properties of
      the nanowires in vacuum. Single Sb2Se3 nanowires with different diameters and
      nanowire bundles were carefully placed on the device to bridge the two membranes.
      The relationship of temperature difference on each heating/sensing suspension
      membranes with joule heating was accurately determined. A single Sb2Se3 nanowire
      with a diameter of ~ 680 nm was found to have a thermal conductivity (kNW) of
      0.037 +/- 0.002 W/m.K. The thermal conductivity of the nanowires is more than an
      order of magnitude lower than that of bulk materials (k ~ 0.36-1.9 W/m.K) and
      highly conductive (sigma ~ 3 * 104 S/m) Sb2Se3 single nanowires (k ~ 1 W/m.K).
      The measured Seebeck coefficient with a positive value of ~ 661 MUV/K is
      comparable to that of highly conductive Sb2Se3 single nanowires (~ 750 MUV/K).
      The thermal transport between wires with different diameters and nanowire bundles
      was compared and discussed.

PMID- 27713528
TI  - Heat-induced phytohormone changes are associated with disrupted early
      reproductive development and reduced yield in rice.
AB  - Heat stress causes morphological and physiological changes and reduces crop yield
      in rice (Oryza sativa). To investigate changes in phytohormones and their
      relationships with yield and other attributes under heat stress, four rice
      varieties (Nagina22, Huanghuazhan, Liangyoupeijiu, and Shanyou 63) were grown in
      pots and subjected to three high temperature treatments plus control in
      temperature-controlled greenhouses for 15 d during the early reproductive phase.
      Yield reductions in Nagina22, Huanghuazhan, and Liangyoupeijiu were attributed to
      reductions in spikelet fertility, spikelets per panicle, and grain weight. The
      adverse effects of high temperature were alleviated by application of exogenous 6
      benzylaminopurine (6-BA) in the heat-susceptible Liangyoupeijiu. High temperature
      stress reduced active cytokinins, gibberellin A1 (GA1), and indole-3-acetic acid
      (IAA), but increased abscisic acid (ABA) and bound cytokinins in young panicles.
      Correlation analyses and application of exogenous 6-BA revealed that high
      temperature-induced cytokinin changes may regulate yield components by modulating
      the differentiation and degradation of branches and spikelets, panicle exsertion,
      pollen vigor, anther dehiscence, and grain size. Heat-tolerant Shanyou 63
      displayed minor changes in phytohormones, panicle formation, and grain yield
      under high temperature compared with those of the other three varieties. These
      results suggest that phytohormone changes are closely associated with yield
      formation, and a small reduction or stability in phytohormone content is required
      to avoid large yield losses under heat stress.

PMID- 27713529
TI  - A novel proposal of a simplified bacterial gene set and the neo-construction of a
      general minimized metabolic network.
AB  - A minimal gene set (MGS) is critical for the assembly of a minimal artificial
      cell. We have developed a proposal of simplifying bacterial gene set to
      approximate a bacterial MGS by the following procedure. First, we base our
      simplified bacterial gene set (SBGS) on experimentally determined essential genes
      to ensure that the genes included in the SBGS are critical. Second, we introduced
      a half-retaining strategy to extract persistent essential genes to ensure
      stability. Third, we constructed a viable metabolic network to supplement SBGS.
      The proposed SBGS includes 327 genes and required 431 reactions. This report
      describes an SBGS that preserves both self-replication and self-maintenance
      systems. In the minimized metabolic network, we identified five novel hub
      metabolites and confirmed 20 known hubs. Highly essential genes were found to
      distribute the connecting metabolites into more reactions. Based on our SBGS, we
      expanded the pool of targets for designing broad-spectrum antibacterial drugs to
      reduce pathogen resistance. We also suggested a rough semi-de novo strategy to
      synthesize an artificial cell, with potential applications in industry.

PMID- 27713530
TI  - A probabilistic assessment of the likelihood of vegetation drought under varying
      climate conditions across China.
AB  - Climate change significantly impacts the vegetation growth and terrestrial
      ecosystems. Using satellite remote sensing observations, here we focus on
      investigating vegetation dynamics and the likelihood of vegetation-related
      drought under varying climate conditions across China. We first compare temporal
      trends of Normalized Difference Vegetation Index (NDVI) and climatic variables
      over China. We find that in fact there is no significant change in vegetation
      over the cold regions where warming is significant. Then, we propose a joint
      probability model to estimate the likelihood of vegetation-related drought
      conditioned on different precipitation/temperature scenarios in growing season
      across China. To the best of our knowledge, this study is the first to examine
      the vegetation-related drought risk over China from a perspective based on joint
      probability. Our results demonstrate risk patterns of vegetation-related drought
      under both low and high precipitation/temperature conditions. We further identify
      the variations in vegetation-related drought risk under different climate
      conditions and the sensitivity of drought risk to climate variability. These
      findings provide insights for decision makers to evaluate drought risk and
      vegetation-related develop drought mitigation strategies over China in a warming
      world. The proposed methodology also has a great potential to be applied for
      vegetation-related drought risk assessment in other regions worldwide.

PMID- 27713531
TI  - Translation Elongation Factor eEF1A2 is a Novel Anticancer Target for the Marine
      Natural Product Plitidepsin.
AB  - eEF1A2 is one of the isoforms of the alpha subunit of the eukaryotic Elongation
      Factor 1. It is overexpressed in human tumors and is endowed with oncogenic
      properties, favoring tumor cell proliferation while inhibiting apoptosis. We
      demonstrate that plitidepsin, an antitumor agent of marine origin that has
      successfully completed a phase-III clinical trial for multiple myeloma, exerts
      its antitumor activity by targeting eEF1A2. The drug interacts with eEF1A2 with a
      KD of 80 nM and a target residence time of circa 9 min. This protein was also
      identified as capable of binding [14C]-plitidepsin in a cell lysate from K-562
      tumor cells. A molecular modelling approach was used to identify a favorable
      binding site for plitidepsin at the interface between domains 1 and 2 of eEF1A2
      in the GTP conformation. Three tumor cell lines selected for at least 100-fold
      more resistance to plitidepsin than their respective parental cells showed
      reduced levels of eEF1A2 protein. Ectopic expression of eEF1A2 in resistant cells
      restored the sensitivity to plitidepsin. FLIM-phasor FRET experiments
      demonstrated that plitidepsin localizes in tumor cells sufficiently close to
      eEF1A2 as to suggest the formation of drug-protein complexes in living cells.
      Altogether, our results strongly suggest that eEF1A2 is the primary target of
      plitidepsin.

PMID- 27713533
TI  - Comprehensive mutational analysis of primary and relapse acute promyelocytic
      leukemia.

PMID- 27713532
TI  - PB1 as a potential target for increasing the breadth of T-cell mediated immunity
      to Influenza A.
AB  - Recently, we showed that combined intranasal and subcutaneous immunization with a
      non-replicating adenoviral vector expressing NP of influenza A, strain PR8,
      induced long-standing protection against a range of influenza A viruses. However,
      H-2b mice challenged with an influenza A strain mutated in the dominant NP366
      epitope were not efficiently protected. To address this problem, we envision the
      use of a cocktail of adenovectors targeting different internal proteins of
      influenza A virus. Consequently, we investigated the possibility of using PB1 as
      a target for an adenovector-based vaccine against influenza A. Our results showed
      that PB1 is not as immunogenic as the NP protein. However, by tethering PB1 to
      the murine invariant chain we were able to circumvent this problem and raise
      quite high numbers of PB1-specific CD8+ T cells in the circulation. Nevertheless,
      mice immunized against PB1 were not as efficiently protected against influenza A
      challenge as similarly NP-vaccinated animals. The reason for this is not a
      difference in the quality of the primed cells, nor in functional avidity.
      However, under similar conditions of immunization fewer PB1-specific cells were
      recruited to the airways, and surface expression of the dominant PB1 peptide,
      PB1703, was less stable than in the case of NP366.

PMID- 27713534
TI  - Moku virus; a new Iflavirus found in wasps, honey bees and Varroa.
AB  - There is an increasing global trend of emerging infectious diseases (EIDs)
      affecting a wide range of species, including honey bees. The global epidemic of
      the single stranded RNA Deformed wing virus (DWV), driven by the spread of Varroa
      destructor has been well documented. However, DWV is just one of many insect RNA
      viruses which infect a wide range of hosts. Here we report the full genome
      sequence of a novel Iflavirus named Moku virus (MV), discovered in the social
      wasp Vespula pensylvanica collected in Hawaii. The novel genome is 10,056
      nucleotides long and encodes a polyprotein of 3050 amino acids. Phylogenetic
      analysis showed that MV is most closely related to Slow bee paralysis virus
      (SBPV), which is highly virulent in honey bees but rarely detected. Worryingly,
      MV sequences were also detected in honey bees and Varroa from the same location,
      suggesting that MV can also infect other hymenopteran and Acari hosts.

PMID- 27713535
TI  - The effect of topical atropine on the choroidal thickness of healthy children.
AB  - The purpose of the current study was to investigate the effect of topical
      atropine on choroidal thickness using spectral-domain optical coherence
      tomography. A total of 30 healthy eyes from 30 children were analyzed in this
      study. A single drop of 1% atropine gel was administered twice daily for a week.
      Choroidal thickness (CT) was measured using SD-OCT, and changes in CT before and
      after administration of the eye drops were analyzed at the subfovea and at 1.0-mm
      intervals (up to 3.0 mm) from the fovea at superior, inferior, nasal, and
      temporal locations. Pre- and post-cycloplegic axial length (AL) was also measured
      using the IOLMaster. We observed that administration of 1% atropine gel led to a
      significant increase in the choroidal thickness under the fovea and at all
      intervals from the fovea. The greatest change in CT was observed in the inferior
      meridian, while the nasal meridian exhibited the least change. AL did not
      significantly differ before and after cycloplegia, and there was no significant
      correlation between the changes in AL and subfoveal CT. It was concluded that
      administration of 1% atropine gel can significantly increase CT in the eyes of
      young Chinese children, albeit with different magnitude at different locations.

PMID- 27713536
TI  - A fast and effective approach for reversible wetting-dewetting transitions on ZnO
      nanowires.
AB  - Here, we demonstrate a facile approach for the preparation of ZnO nanowires (NWs)
      with tunable surface wettability that can be manipulated reversibly in a
      controlled manner from a superhydrophilic state to a superhydrophobic state. The
      as-synthesized ZnO NWs obtained by a chemical vapor deposition method are
      superhydrophilic with a contact angle (CA) value of ~0 degrees . After H2 gas
      annealing at 300  degrees C for 90 minutes, ZnO NWs display superhydrophobic
      behavior with a roll-off angle less than 5 degrees . However, O2 gas annealing
      converts these superhydrophobic ZnO NWs into a superhydrophilic state. For
      switching from superhydrophobic to superhydrophilic state and vice versa in
      cyclic manner, H2 and O2 gas annealing treatment was used, respectively. A model
      based on density functional theory indicates that the oxygen-related defects are
      responsible for CA switching. The water resistant properties of the ZnO NWs
      coating is found to be durable and can be applied to a variety of substrates
      including glass, metals, semiconductors, paper and even flexible polymers.

PMID- 27713537
TI  - Increasing the Efficiency of CRISPR/Cas9-mediated Precise Genome Editing of HSV-1
      Virus in Human Cells.
AB  - Genetically modified HSV-1 viruses serve as promising vectors for tumour therapy
      and vaccine development. The CRISPR/Cas9 system is one of the most powerful tools
      for precise gene editing of the genomes of organisms. However, whether the
      CRISPR/Cas9 system can precisely and efficiently make gene replacements in the
      genome of HSV-1 remains essentially unknown. Here, we reported CRISPR/Cas9
      mediated editing of the HSV-1 genome in human cells, including the knockout and
      replacement of large genes. In established cells stably expressing CRISPR/Cas9,
      gRNA in coordination with Cas9 could direct a precise cleavage within a pre
      defined target region, and foreign genes were successfully used to replace the
      target gene seamlessly by HDR-mediated gene replacement. Introducing the NHEJ
      inhibitor SCR7 to the CRISPR/Cas9 system greatly facilitated HDR-mediated gene
      replacement in the HSV-1 genome. We provided the first genetic evidence that two
      copies of the ICP0 gene in different locations on the same HSV-1 genome could be
      simultaneously modified with high efficiency and with no off-target
      modifications. We also developed a revolutionized isolation platform for desired
      recombinant viruses using single-cell sorting. Together, our work provides a
      significantly improved method for targeted editing of DNA viruses, which will
      facilitate the development of anti-cancer oncolytic viruses and vaccines.

PMID- 27713538
TI  - Tooth enamel oxygen "isoscapes" show a high degree of human mobility in
      prehistoric Britain.
AB  - A geostatistical model to predict human skeletal oxygen isotope values
      (delta18Op) in Britain is presented here based on a new dataset of Chalcolithic
      and Early Bronze Age human teeth. The spatial statistics which underpin this
      model allow the identification of individuals interpreted as 'non-local' to the
      areas where they were buried (spatial outliers). A marked variation in delta18Op
      is observed in several areas, including the Stonehenge region, the Peak District,
      and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas,
      rich in funerary and ceremonial monuments, may have formed focal points for
      people, some of whom would have travelled long distances, ultimately being buried
      there. The dataset and model represent a baseline for future archaeological
      studies, avoiding the complex conversions from skeletal to water delta18O values
      a process known to be problematic.

PMID- 27713539
TI  - Mechanism of high affinity inhibition of the human urate transporter URAT1.
AB  - Gout is caused by elevated serum urate levels, which can be treated using
      inhibitors of the uric acid transporter, URAT1. We exploited affinity differences
      between the human and rat transporters to map inhibitor binding sites in URAT1.
      Human-rat transporter chimeras revealed that human URAT1 serine-35, phenylalanine
      365 and isoleucine-481 are necessary and sufficient to provide up to a 100-fold
      increase in affinity for inhibitors. Moreover, serine-35 and phenylalanine-365
      are important for high-affinity interaction with the substrate urate. A novel
      URAT1 binding assay provides support for direct interaction with these amino
      acids; thus, current clinically important URAT1 inhibitors likely bind the same
      site in URAT1. A structural model suggests that these three URAT1 residues are in
      close proximity potentially projecting within the channel. Our results indicate
      that amino acids from several transmembrane segments functionally cooperate to
      form a high-affinity URAT1 inhibitor binding site that, when occupied, prevents
      substrate interactions.

PMID- 27713540
TI  - Polar Superhelices in Ferroelectric Chiral Nanosprings.
AB  - Topological objects of nontrivial spin or dipolar field textures, such as
      skyrmions, merons, and vortices, interacting with applied external fields in
      ferroic materials are of great scientific interest as an intriguing playground of
      unique physical phenomena and novel technological paradigms. The quest for new
      topological configurations of such swirling field textures has primarily been
      done for magnets with Dzyaloshinskii-Moriya interactions, while the absence of
      such intrinsic chiral interactions among electric dipoles left ferroelectrics
      aside in this quest. Here, we demonstrate that a helical polarization coiled into
      another helix, namely a polar superhelix, can be extrinsically stabilized in
      ferroelectric nanosprings. The interplay between dipolar interactions confined in
      the chiral geometry and the complex strain field of mixed bending and twisting
      induces the superhelical configuration of electric polarization. The geometrical
      structure of the polar superhelix gives rise to electric chiralities at two
      different length scales and the coexistence of three order parameters, i.e.,
      polarization, toroidization, and hypertoroidization, both of which can be
      manipulated by homogeneous electric and/or mechanical fields. Our work therefore
      provides a new geometrical configuration of swirling dipolar fields, which offers
      the possibility of multiple order-parameters, and electromechanically
      controllable dipolar chiralities and associated electro-optical responses.

PMID- 27713541
TI  - Femtosecond dynamics of energetic electrons in high intensity laser-matter
      interactions.
AB  - Highly energetic electrons are generated at the early phases of the interaction
      of short-pulse high-intensity lasers with solid targets. These escaping particles
      are identified as the essential core of picosecond-scale phenomena such as laser
      based acceleration, surface manipulation, generation of intense magnetic fields
      and electromagnetic pulses. Increasing the number of the escaping electrons
      facilitate the late time processes in all cases. Up to now only indirect
      evidences of these important forerunners have been recorded, thus no detailed
      study of the governing mechanisms was possible. Here we report, for the first
      time, direct time-dependent measurements of energetic electrons ejected from
      solid targets by the interaction with a short-pulse high-intensity laser. We
      measured electron bunches up to 7 nanocoulombs charge, picosecond duration and 12
      megaelectronvolts energy. Our 'snapshots' capture their evolution with an
      unprecedented temporal resolution, demonstrat- ing a significant boost in charge
      and energy of escaping electrons when increasing the geometrical target
      curvature. These results pave the way toward significant improvement in laser
      acceleration of ions using shaped targets allowing the future development of
      small scale laser-ion accelerators.

PMID- 27713542
TI  - Electrostatic repulsive out-of-plane actuator using conductive substrate.
AB  - A pseudo-three-layer electrostatic repulsive out-of-plane actuator is proposed.
      It combines the advantages of two-layer and three-layer repulsive actuators,
      i.e., fabrication requirements and fill factor. A theoretical model for the
      proposed actuator is developed and solved through the numerical calculation of
      Schwarz-Christoffel mapping. Theoretical and simulated results show that the
      pseudo-three-layer actuator offers higher performance than the two-layer and
      three-layer actuators with regard to the two most important characteristics of
      actuators, namely, driving force and theoretical stroke. Given that the pseudo
      three-layer actuator structure is compatible with both the parallel-plate
      actuators and these two types of repulsive actuators, a 19-element two-layer
      repulsive actuated deformable mirror is operated in pseudo-three-layer electrical
      connection mode. Theoretical and experimental results demonstrate that the pseudo
      three-layer mode produces a larger displacement of 0-4.5 MUm for a dc driving
      voltage of 0-100 V, when compared with that in two-layer mode.

PMID- 27713543
TI  - Tumour metabolism: Lactic acid: not just a waste product?

PMID- 27713544
TI  - AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing
      of hematopoietic stem/progenitor cells.
AB  - The AML1/ETO fusion protein found in acute myeloid leukemias functions as a
      transcriptional regulator by recruiting co-repressor complexes to its DNA binding
      site. In order to extend the understanding of its role in preleukemia, we
      expressed AML1/ETO in a murine immortalized pluripotent hematopoietic
      stem/progenitor cell line, EML C1, and found that genes involved in functions
      such as cell-to-cell adhesion and cell motility were among the most significantly
      regulated as determined by RNA sequencing. In functional assays, AML1/ETO
      expressing cells showed a decrease in adhesion to stromal cells, an increase of
      cell migration rate in vitro, and displayed an impairment in homing and
      engraftment in vivo upon transplantation into recipient mice. Our results suggest
      that AML1/ETO expression determines a more mobile and less adherent phenotype in
      preleukemic cells, therefore altering the interaction with the hematopoietic
      niche, potentially leading to the migration across the bone marrow barrier and to
      disease progression.

PMID- 27713545
TI  - Fully inkjet-printed microfluidics: a solution to low-cost rapid three
      dimensional microfluidics fabrication with numerous electrical and sensing
      applications.
AB  - As the needs for low-cost rapidly-produced microfluidics are growing with the
      trend of Lab-on-a-Chip and distributed healthcare, the fully inkjet-printing of
      microfluidics can be a solution to it with numerous potential electrical and
      sensing applications. Inkjet-printing is an additive manufacturing technique
      featuring no material waste and a low equipment cost. Moreover, similar to other
      additive manufacturing techniques, inkjet-printing is easy to learn and has a
      high fabrication speed, while it offers generally a great planar resolution down
      to below 20 um and enables flexible designs due to its inherent thin film
      deposition capabilities. Due to the thin film feature, the printed objects also
      usually obtain a high vertical resolution (such as 4.6 um). This paper introduces
      a low-cost rapid three-dimensional fabrication process of microfluidics, that
      relies entirely on an inkjet-printer based single platform and can be implemented
      directly on top of virtually any substrates.

PMID- 27713546
TI  - Testing multi-scale processing in the auditory system.
AB  - Natural sounds contain information on multiple timescales, so the auditory system
      must analyze and integrate acoustic information on those different scales to
      extract behaviorally relevant information. However, this multi-scale process in
      the auditory system is not widely investigated in the literature, and existing
      models of temporal integration are mainly built upon detection or recognition
      tasks on a single timescale. Here we use a paradigm requiring processing on
      relatively 'local' and 'global' scales and provide evidence suggesting that the
      auditory system extracts fine-detail acoustic information using short temporal
      windows and uses long temporal windows to abstract global acoustic patterns.
      Behavioral task performance that requires processing fine-detail information does
      not improve with longer stimulus length, contrary to predictions of previous
      temporal integration models such as the multiple-looks and the spectro-temporal
      excitation pattern model. Moreover, the perceptual construction of putatively
      'unitary' auditory events requires more than hundreds of milliseconds. These
      findings support the hypothesis of a dual-scale processing likely implemented in
      the auditory cortex.

PMID- 27713547
TI  - Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic
      Properties.
AB  - Acupuncture as a therapeutic intervention has been widely used for treatment of
      many pathophysiological disorders. For achieving improved therapeutic effects,
      relatively thick acupuncture needles have been frequently used in clinical
      practice with, in turn, enhanced stimulation intensity. However due to the
      discomforting nature of the larger-diameter acupuncture needles there is
      considerable interest in developing advanced acupuncture therapeutical techniques
      that provide more comfort with improved efficacy. So motivated, we have developed
      a new class of acupuncture needles, porous acupuncture needles (PANs) with
      hierarchical micro/nano-scale conical pores upon the surface, fabricated via a
      simple and well known electrochemical process, with surface area approximately 20
      times greater than conventional acupuncture needles. The performance of these
      high-surface-area PANs is evaluated by monitoring the electrophysiological and
      behavioral responses from the in vivo stimulation of Shenmen (HT7) points in
      Wistar rats, showing PANs to be more effective in controlling
      electrophysiological and behavioral responses than conventional acupuncture
      needles. Comparative analysis of cocaine induced locomotor activity using PANs
      and thick acupuncture needles shows enhanced performance of PANs with
      significantly less pain sensation. Our work offers a unique pathway for achieving
      a comfortable and improved acupuncture therapeutic effect.

PMID- 27713548
TI  - Intra-islet lesions and lobular variations in beta-cell mass expansion in ob/ob
      mice revealed by 3D imaging of intact pancreas.
AB  - The leptin deficient ob/ob mouse is a widely used model for studies on initial
      aspects of metabolic disturbances leading to type 2 diabetes, including insulin
      resistance and obesity. Although it is generally accepted that ob/ob mice display
      a dramatic increase in beta-cell mass to compensate for increased insulin demand,
      the spatial and quantitative dynamics of beta-cell mass distribution in this
      model has not been assessed by modern optical 3D imaging techniques. We applied
      optical projection tomography and ultramicroscopy imaging to extract information
      about individual islet beta-cell volumes throughout the volume of ob/ob pancreas
      between 4 and 52 weeks of age. Our data show that cystic lesions constitute a
      significant volume of the hyperplastic ob/ob islets. We propose that these
      lesions are formed by a mechanism involving extravasation of red blood
      cells/plasma due to increased islet vessel blood flow and vessel instability.
      Further, our data indicate that the primary lobular compartments of the ob/ob
      pancreas have different potentials for expanding their beta-cell population.
      Unawareness of the characteristics of beta-cell expansion in ob/ob mice presented
      in this report may significantly influence ex vivo and in vivo assessments of
      this model in studies of beta-cell adaptation and function.

PMID- 27713549
TI  - A study of the temporal robustness of the growing global container-shipping
      network.
AB  - Whether they thrive as they grow must be determined for all constantly expanding
      networks. However, few studies have focused on this important network feature or
      the development of quantitative analytical methods. Given the formation and
      growth of the global container-shipping network, we proposed the concept of
      network temporal robustness and quantitative method. As an example, we collected
      container liner companies' data at two time points (2004 and 2014) and built a
      shipping network with ports as nodes and routes as links. We thus obtained a
      quantitative value of the temporal robustness. The temporal robustness is a
      significant network property because, for the first time, we can clearly
      recognize that the shipping network has become more vulnerable to damage over the
      last decade: When the node failure scale reached 50% of the entire network, the
      temporal robustness was approximately -0.51% for random errors and -12.63% for
      intentional attacks. The proposed concept and analytical method described in this
      paper are significant for other network studies.

PMID- 27713550
TI  - Chromatic Mechanical Response in 2-D Layered Transition Metal Dichalcogenide
      (TMDs) based Nanocomposites.
AB  - The ability to convert photons of different wavelengths directly into mechanical
      motion is of significant interest in many energy conversion and reconfigurable
      technologies. Here, using few layer 2H-MoS2 nanosheets, layer by layer process of
      nanocomposite fabrication, and strain engineering, we demonstrate a reversible
      and chromatic mechanical response in MoS2-nanocomposites between 405 nm to 808 nm
      with large stress release. The chromatic mechanical response originates from the
      d orbitals and is related to the strength of the direct exciton resonance A and B
      of the few layer 2H-MoS2 affecting optical absorption and subsequent mechanical
      response of the nanocomposite. Applying uniaxial tensile strains to the
      semiconducting few-layer 2H-MoS2 crystals in the nanocomposite resulted in
      spatially varying energy levels inside the nanocomposite that enhanced the
      broadband optical absorption up to 2.3 eV and subsequent mechanical response. The
      unique photomechanical response in 2H-MoS2 based nanocomposites is a result of
      the rich d electron physics not available to nanocomposites based on sp bonded
      graphene and carbon nanotubes, as well as nanocomposite based on metallic
      nanoparticles. The reversible strain dependent optical absorption suggest
      applications in broad range of energy conversion technologies that is not
      achievable using conventional thin film semiconductors.

PMID- 27713551
TI  - Pomegranate extract decreases oxidative stress and alleviates mitochondrial
      impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of
      spontaneously hypertensive rats.
AB  - High blood pressure, or "hypertension," is associated with high levels of
      oxidative stress in the paraventricular nucleus of the hypothalamus. While
      pomegranate extract is a known antioxidant that is thought to have
      antihypertensive effects, the mechanism whereby pomegranate extract lowers blood
      pressure and the tissue that mediates its antihypertensive effects are currently
      unknown. We have used a spontaneously hypertensive rat model to investigate the
      antihypertensive properties of pomegranate extract. We found that chronic
      treatment of hypertensive rats with pomegranate extract significantly reduced
      blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced
      oxidative stress, increased the antioxidant defense system, and decreased
      inflammation in the paraventricular nucleus of hypertensive rats. We determined
      that pomegranate extract reduced mitochondrial superoxide anion levels and
      increased mitochondrial function in the paraventricular nucleus of hypertensive
      rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics
      and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45
      related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract
      reduces oxidative stress in the paraventricular nucleus to relieve hypertension.
      Our findings demonstrate that pomegranate extract alleviates hypertension by
      reducing oxidative stress and improving mitochondrial function in the
      paraventricular nucleus, and reveal multiple novel targets for therapeutic
      treatment of hypertension.

PMID- 27713553
TI  - SCIWORA.

PMID- 27713552
TI  - Differential transcriptional responses to Ebola and Marburg virus infection in
      bat and human cells.
AB  - The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases
      and 11,000 deaths, underlining the need for a better understanding of the biology
      of this highly pathogenic virus to develop specific counter strategies. Two
      filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal
      infection in humans. However, bats are natural hosts and survive filovirus
      infections without obvious symptoms. The molecular basis of this striking
      difference in the response to filovirus infections is not well understood. We
      report a systematic overview of differentially expressed genes, activity motifs
      and pathways in human and bat cells infected with the Ebola and Marburg viruses,
      and we demonstrate that the replication of filoviruses is more rapid in human
      cells than in bat cells. We also found that the most strongly regulated genes
      upon filovirus infection are chemokine ligands and transcription factors. We
      observed a strong induction of the JAK/STAT pathway, of several genes encoding
      inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER
      stress-induced cell death. We used comparative transcriptomics to provide a data
      resource that can be used to identify cellular responses that might allow bats to
      survive filovirus infections.

PMID- 27713556
TI  - Non-equilibrium quantum phase transition via entanglement decoherence dynamics.
AB  - We investigate the decoherence dynamics of continuous variable entanglement as
      the system-environment coupling strength varies from the weak-coupling to the
      strong-coupling regimes. Due to the existence of localized modes in the strong
      coupling regime, the system cannot approach equilibrium with its environment,
      which induces a nonequilibrium quantum phase transition. We analytically solve
      the entanglement decoherence dynamics for an arbitrary spectral density. The
      nonequilibrium quantum phase transition is demonstrated as the system-environment
      coupling strength varies for all the Ohmic-type spectral densities. The 3-D
      entanglement quantum phase diagram is obtained.

PMID- 27713554
TI  - Glibenclamide impairs responses of neutrophils against Burkholderia pseudomallei
      by reduction of intracellular glutathione.
AB  - The major risk factor for melioidosis, an infectious disease caused by B.
      pseudomallei, is diabetes mellitus. More than half of diabetic melioidosis
      patients in Thailand were prescribed glibenclamide. Recent evidence demonstrates
      that glibenclamide reduces pro-inflammatory cytokine production by
      polymorphonuclear neutrophils (PMNs) of diabetic individuals in response to this
      bacterial infection. However, the mechanisms by which glibenclamide affects
      cytokine production are unknown. We found that PMNs from glibenclamide-treated
      diabetic individuals infected with live B. pseudomallei in vitro showed lower
      free glutathione (GSH) levels compared with those of healthy individuals.
      Glibenclamide decreased GSH levels and glutathione peroxidase (GPx) of PMNs after
      exposed to live B. pseudomallei. Moreover, glibenclamide reduced cytokine
      production and migration capacity of infected PMNs, whereas GSH could restore
      these functions. Taken together, our data show a link between the effect of
      glibenclamide on GSH and PMN functions in response to B. pseudomallei that may
      contribute to the susceptibility of diabetic individuals to B. pseudomallei
      infection.

PMID- 27713557
TI  - Olfactory experiences dynamically regulate plasticity of dendritic spines in
      granule cells of Xenopus tadpoles in vivo.
AB  - Granule cells, rich in dendrites with densely punctated dendritic spines, are the
      most abundant inhibitory interneurons in the olfactory bulb. The dendritic spines
      of granule cells undergo remodeling during the development of the nervous system.
      The morphological plasticity of the spines' response to different olfactory
      experiences in vivo is not fully known. In initial studies, a single granule cell
      in Xenopus tadpoles was labeled with GFP plasmids via cell electroporation; then,
      morphologic changes of the granule cell spines were visualized by in vivo
      confocal time-lapse imaging. With the help of long-term imaging, the total spine
      density, dynamics, and stability of four types of dendritic spines (mushroom,
      stubby, thin and filopodia) were obtained. Morphological analysis demonstrated
      that odor enrichment produced a remarkable increase in the spine density and
      stability of large mushroom spine. Then, with the help of short-term imaging, we
      analyzed the morphological transitions among different spines. We found that
      transitions between small spines (thin and filopodia) were more easily influenced
      by odor stimulation or olfactory deprivation. These results indicate that
      different olfactory experiences can regulate the morphological plasticity of
      different dendritic spines in the granule cell.

PMID- 27713555
TI  - Lipid metabolism is associated with developmental epigenetic programming.
AB  - Maternal diet and metabolism impact fetal development. Epigenetic reprogramming
      facilitates fetal adaptation to these in utero cues. To determine if maternal
      metabolite levels impact infant DNA methylation globally and at growth and
      development genes, we followed a clinical birth cohort of 40 mother-infant dyads.
      Targeted metabolomics and quantitative DNA methylation were analyzed in 1st
      trimester maternal plasma (M1) and delivery maternal plasma (M2) as well as
      infant umbilical cord blood plasma (CB). We found very long chain fatty acids,
      medium chain acylcarnitines, and histidine were: (1) stable in maternal plasma
      from pregnancy to delivery, (2) significantly correlated between M1, M2, and CB,
      and (3) in the top 10% of maternal metabolites correlating with infant DNA
      methylation, suggesting maternal metabolites associated with infant DNA
      methylation are tightly controlled. Global DNA methylation was highly correlated
      across M1, M2, and CB. Thus, circulating maternal lipids are associated with
      developmental epigenetic programming, which in turn may impact lifelong health
      and disease risk. Further studies are required to determine the causal link
      between maternal plasma lipids and infant DNA methylation patterns.

PMID- 27713558
TI  - Occurrence and preliminarily environmental risk assessment of selected
      pharmaceuticals in the urban rivers, China.
AB  - Twelve selected pharmaceuticals including antibiotics, analgesics, antiepileptics
      and lipid regulators were analysed and detected in water samples collected from
      18 sampling sections along the three main urban rivers in Yangpu District of
      Shanghai, China during four sampling campaigns. Besides, algal growth inhibition
      test was conducted to preliminarily assess the eco-toxicology induced by the
      target pharmaceuticals in the rivers. Mean levels for most of target compounds
      were generally below 100 ng/L at sampling sections, with the exception of
      caffeine and paracetamol presenting considerably high concentration. The detected
      pharmaceuticals in the urban rivers ranged from <LOQ for propranolol to 8571 ng/L
      for caffeine. Qiujiang River could be regarded as the most polluted according to
      total detected pharmaceutical concentrations. The target pharmaceuticals varied
      and fluctuated irregularly from the upstreams to the downstreams of the three
      rivers, indicating the wastewater inputs from non-point sources and their
      individual different characteristics of transference and transportation.
      Preliminary eco-toxicological risk assessment showed that the presence of
      azithromycin, clarithromycin and caffeine may present an ecotoxicological risk in
      the urban rivers. For other tested pharmaceuticals the inhibition effects of
      single substances in the urban aquatic environment, based on the algae inhibition
      tests, were very imperceptible.

PMID- 27713559
TI  - A novel Fe(III) dependent bioflocculant from Klebsiella oxytoca GS-4-08: culture
      conditions optimization and flocculation mechanism.
AB  - In this work, the effect of cultivation factors on the flocculation efficiency
      (FE) of bioflocculant P-GS408 from Klebsiella oxytoca was optimized by the
      response surface methodology. The most significant factor, i.e. culture time, was
      determined by gray relational analysis. A total of 240 mg of purified P-GS408 was
      prepared from 1 liter of culture solution under the optimal conditions. GC-MS
      analysis results indicated that the polysaccharide of P-GS408 mainly contains
      Rhamnose and Galactose, and the existence of abundant hydroxyl, carboxyl and
      amino groups was evidenced by FTIR and XPS analyses. With the aid of Fe3+, the FE
      of kaolin solution by P-GS408 could achieve 99.48% in ten minutes. Functional
      groups of polysaccharide were involved in the first adsorption step and the zeta
      potential of kaolin solution changed from -39.0 mV to 43.4 mV in the presence of
      Fe3+ and P-GS408. Three-dimensional excitation-emission (EEM) fluorescence
      spectra demonstrates that the trivalent Fe3+ and Al3+ can bind efficiently with P
      GS408, while those univalent and divalent cations cannot. With the help of SEM
      images, FTIR, zeta potential and EEM spectra, we proposed the P-GS408
      flocculation mechanism, which consists of coordination bond combination, charge
      neutrality, adsorption and bridging, and net catching.

PMID- 27713560
TI  - Efficient Enrichment of Bacterial mRNA from Host-Bacteria Total RNA Samples.
AB  - Despite numerous advances in genomics and bioinformatics, technological hurdles
      remain to examine host-microbe transcriptomics. Sometimes the transcriptome of
      either or both can be ascertained merely by generating more sequencing reads.
      However, many cases exist where bacterial mRNA needs to be enriched further to
      enable cost-effective sequencing of the pathogen or endosymbiont. While a
      suitable method is commercially available for mammalian samples of this type,
      development of such methods has languished for invertebrate samples. Furthermore,
      a common method across multiple taxa would facilitate comparisons between
      bacteria in invertebrate vectors and their vertebrate hosts. Here, a method is
      described to concurrently remove polyadenylated transcripts, prokaryotic rRNA,
      and eukaryotic rRNA, including those with low amounts of starting material (e.g.
      100 ng). In a Wolbachia-Drosophila system, this bacterial mRNA enrichment yielded
      a 3-fold increase in Wolbachia mRNA abundance and a concomitant 3.3-fold increase
      in the percentage of transcripts detected. More specifically, 70% of the genome
      could be recovered by transcriptome sequencing compared to 21% in the total RNA.
      Sequencing of similar bacterial mRNA-enriched samples generated from Ehrlichia
      infected canine cells covers 93% of the Ehrlichia genome, suggesting ubiquitous
      transcription across the entire Ehrlichia chaffeensis genome. This technique can
      potentially be used to enrich bacterial mRNA in many studies of host-microbe
      interactions.

PMID- 27713561
TI  - Characterisation of sensitivity and orientation tuning for visually responsive
      ensembles in the zebrafish tectum.
AB  - Sensory coding relies on ensembles of co-active neurons, but these ensembles
      change from trial to trial of the same stimulus. This is due in part to wide
      variability in the responsiveness of neurons within these ensembles, with some
      neurons responding regularly to a stimulus while others respond inconsistently.
      The specific functional properties that cause neurons to respond more or less
      consistently have not been thoroughly explored. Here, we have examined neuronal
      ensembles in the zebrafish tectum responsive to repeated presentations of a
      visual stimulus, and have explored how these populations change when the
      orientation or brightness of the stimulus is altered. We found a continuum of
      response probabilities across the neurons in the visual ensembles, with the most
      responsive neurons focused toward the spatial centre of the ensemble. As the
      visual stimulus was made dimmer, these neurons remained active, suggesting higher
      overall responsiveness. However, these cells appeared to represent the most
      consistent end of a continuum, rather than a functionally distinct "core" of
      highly responsive neurons. Reliably responsive cells were broadly tuned to a
      range of stimulus orientations suggesting that, at least for this stimulus
      property, tight stimulus tuning was not responsible for their consistent
      responses.

PMID- 27713562
TI  - New interpretation of the Gran Dolina-TD6 bearing Homo antecessor deposits
      through sedimentological analysis.
AB  - Gran Dolina is a cavity infilled by at least 25 m of Pleistocene sediments. This
      sequence contains the TD6 stratigraphic unit, whose records include around 170
      hominin bones that have allowed the definition of a new species, Homo antecessor.
      This fossil accumulation was studied as a single assemblage and interpreted as a
      succession of several human home bases. We propose a complete stratigraphic
      context and sedimentological interpretation for TD6, analyzing the relationships
      between the sedimentary facies, the clasts and archaeo-palaeontological remains.
      The TD6 unit has been divided into three sub-units and 13 layers. Nine
      sedimentary facies have been defined. Hominin remains appear related to three
      different sedimentary facies: debris flow facies, channel facies and floodplain
      facies. They show three kinds of distribution: first a group of scattered
      fossils, then a group with layers of fossils in fluvial facies, and third a group
      with a layer of fossils in mixed fluvial and gravity flow facies. The results of
      this work suggest that some of these hominin remains accumulated in the cave by
      geological processes, coming from the adjacent slope above the cave or the cave
      entry, as the palaeogeography and sedimentary characteristics of these
      allochthonous facies suggest.

PMID- 27713563
TI  - Tailoring Thermal Conductivity of Single-stranded Carbon-chain Polymers through
      Atomic Mass Modification.
AB  - Tailoring the thermal conductivity of polymers is central to enlarge their
      applications in the thermal management of flexible integrated circuits. Progress
      has been made over the past decade by fabricating materials with various
      nanostructures, but a clear relationship between various functional groups and
      thermal properties of polymers remains to be established. Here, we numerically
      study the thermal conductivity of single-stranded carbon-chain polymers with
      multiple substituents of hydrogen atoms through atomic mass modification. We find
      that their thermal conductivity can be tuned by atomic mass modifications as
      revealed through molecular dynamics simulations. The simulation results suggest
      that heavy homogeneous substituents do not assist heat transport and trace
      amounts of heavy substituents can in fact hinder heat transport substantially.
      Our analysis indicates that carbon chain has the biggest contribution (over 80%)
      to the thermal conduction in single-stranded carbon-chain polymers. We further
      demonstrate that atomic mass modifications influence the phonon bands of bonding
      carbon atoms, and the discrepancies of phonon bands between carbon atoms are
      responsible for the remarkable drops in thermal conductivity and large thermal
      resistances in carbon chains. Our study provides fundamental insight into how to
      tailor the thermal conductivity of polymers through variable substituents.

PMID- 27713564
TI  - A Nucleotide Signature for the Identification of Angelicae Sinensis Radix
      (Danggui) and Its Products.
AB  - It is very difficult to identify Angelicae sinensis radix (Danggui) when it is
      processed into Chinese patent medicines. The proposed internal transcribed spacer
      2 (ITS2) is not sufficient to resolve heavily processed materials. Therefore, a
      short barcode for the identification of processed materials is urgently needed.
      In this study, 265 samples of Angelicae sinensis radix and adulterants were
      collected. The ITS2 region was sequenced, and based on one single nucleotide
      polymorphism(SNP) site unique to Angelica sinensis, a nucleotide signature
      consisting of 37-bp (5'-aatccgcgtc atcttagtga gctcaaggac ccttagg-3') was
      developed. It is highly conserved and specific within Angelica sinensis while
      divergent among other species. Then, we designed primers (DG01F/DG01R) to amplify
      the nucleotide signature region from processed materials. 15 samples procured
      online were analysed. By seeking the signature, we found that 7 of them were
      counterfeits. 28 batches of Chinese patent medicines containing Danggui were
      amplified. 19 of them were found to contain the signature, and adulterants such
      as Ligusticum sinense, Notopterygium incisum, Angelica decursiva and Angelica
      gigas were detected in other batches. Thus, this nucleotide signature, with only
      37-bp, will broaden the application of DNA barcoding to identify the components
      in decoctions, Chinese patent medicines and other products with degraded DNA.

PMID- 27713566
TI  - A method to calibrate a camera using perpendicularity of 2D lines in the target
      observations.
AB  - Camera calibration based on point features leads the main trends in vision-based
      measurement systems for both fundamental researches and potential applications.
      However, the calibration results tend to be affected by the precision of the
      feature point extraction in the camera images. As the point features are noise
      sensitive, line features are more appropriate to provide a stable calibration due
      to the noise immunity of line features. We propose a calibration method using the
      perpendicularity of the lines on a 2D target. The objective function of the
      camera internal parameters is theoretically constructed by the reverse
      projections of the image lines on a 2D target in the world coordinate system. We
      experimentally explore the performances of the perpendicularity method and
      compare them with the point feature methods at different distances. By the
      perpendicularity and the noise immunity of the lines, our work achieves a
      relatively higher calibration precision.

PMID- 27713565
TI  - Molecular surveillance on Streptococcus pneumoniae carriage in non-elderly
      adults; little evidence for pneumococcal circulation independent from the
      reservoir in children.
AB  - Carriage of Streptococcus pneumoniae in adults is rarely detected by the gold
      standard culture method. With molecular tests of high sensitivity now available,
      we analysed upper respiratory tract samples collected during autumn/winter
      2012/2013 from parents of PCV7-vaccinated infants and from childless adults,
      directly comparing culture and qPCR-based S. pneumoniae detection. As compared to
      the gold standard of testing nasopharyngeal swabs, qPCR-based analysis of oral
      samples significantly improved detection of pneumococcal carriage (5% versus 20%,
      p < 0.0001) with higher carriage rates in parents compared to childless adults
      (34% versus 7%; p < 0.001). Molecular methods also increased the number of
      serotype-carriage events detected with higher carriage frequencies of serotypes 3
      and 7A/F and lower of serotypes 6C/D and 15A/B/C in parents compared to their
      infant children. We provide evidence that culture-based methods severely
      underestimate adult carriage rates and for the superiority of testing oral
      samples over nasopharyngeal swabs. The substantial circulation of pneumococci in
      parents is however, not representative for the entire adult population. While age
      associated differences in serotype carriage suggests reservoirs outside infants
      as potential sources of vaccine-serotypes contributing to weakening of vaccine
      herd effects, we find no evidence for reservoirs in adults contributing to
      serotype replacement in carriage.

PMID- 27713567
TI  - An Animal Model of Modic Changes by Embedding Autogenous Nucleus Pulposus inside
      Subchondral Bone of Lumbar Vertebrae.
AB  - The establishment of Modic changes (MCs) in animal model was vital for research
      of MCs. Fifty-four rabbits were divided into a sham group, a muscle embedment
      group (ME group) and nucleus pulposus (NP) embedment group (NPE group). In the
      NPE group, the discs were exposed by the lumbar anterolateral surgical approach.
      A needle was used to puncture the L5 vertebral body close to the endplate. NP was
      extracted by a syringe from L1/2 intervertebral discs and then injected into the
      drilled hole of subchondral bone. The muscle embedment group and sham group had
      the same procedure and drill method as the NP embedment group. Some pieces of
      muscle were put into the hole in the ME group, but nothing was put into the hole
      in the sham group. After the operation, MRI scan and molecular biology tests were
      applied. The signal changes were found in the NPE group; while the sham group and
      the ME group showed no significant signal change. Histological observation
      confirmed that there was abnormal tissue proliferation in imbed site. High
      expression of IL-4, IL-17 and IFN-gamma were detected in the NPE group. The
      embedment of NP into subchondral bone can create an animal model of MCs.

PMID- 27713568
TI  - Characterisation of the immune compounds in koala milk using a combined
      transcriptomic and proteomic approach.
AB  - Production of milk is a key characteristic of mammals, but the features of
      lactation vary greatly between monotreme, marsupial and eutherian mammals.
      Marsupials have a short gestation followed by a long lactation period, and milk
      constituents vary greatly across lactation. Marsupials are born immunologically
      naive and rely on their mother's milk for immunological protection. Koalas
      (Phascolarctos cinereus) are an iconic Australian species that are increasingly
      threatened by disease. Here we use a mammary transcriptome, two milk proteomes
      and the koala genome to comprehensively characterise the protein components of
      koala milk across lactation, with a focus on immune constituents. The most
      abundant proteins were well-characterised milk proteins, including beta
      lactoglobulin and lactotransferrin. In the mammary transcriptome, 851 immune
      transcripts were expressed, including immunoglobulins and complement components.
      We identified many abundant antimicrobial peptides, as well as novel proteins
      with potential antimicrobial roles. We discovered that marsupial VELP is an
      ortholog of eutherian Glycam1, and likely has an antimicrobial function in milk.
      We also identified highly-abundant koala endogenous-retrovirus sequences,
      identifying a potential transmission route from mother to young. Characterising
      the immune components of milk is key to understanding protection of marsupial
      young, and the novel immune compounds identified may have applications in
      clinical research.

PMID- 27713569
TI  - Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via
      Tdg in the mouse liver.
AB  - The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that
      plays an important role in the manifestation of toxicity induced by polycyclic
      aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical
      biotransformation through activation of drug metabolizing enzymes. The activated
      Ahr cooperates with coactivator complexes to induce epigenetic modifications at
      target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the
      Ahr target gene cytochrome P450 1a1 (Cyp1a1). A single dose of TCDD administered
      to adult mice induced Ahr-dependent CpG hypomethylation, changes in histone
      modifications, and thymine DNA glycosylase (Tdg) recruitment at the Cyp1a1
      promoter in the liver within 24 hrs. These epigenetic changes persisted until 40
      days post-TCDD treatment and there was Cyp1a1 mRNA hyperinduction upon repeat
      administration of TCDD at this time-point. Our demethylation assay using siRNA
      knockdown and an in vitro methylated plasmid showed that Ahr, Tdg, and the ten
      eleven translocation methyldioxygenases Tet2 and Tet3 are required for the TCDD
      induced DNA demethylation. These results provide novel evidence of Ahr-driven
      active DNA demethylation and epigenetic memory. The epigenetic alterations
      influence response to subsequent chemical exposure and imply an adaptive
      mechanism to xenobiotic stress.

PMID- 27713570
TI  - Quantitative Profiling of Single Formalin Fixed Tumour Sections: proteomics for
      translational research.
AB  - Although re-sequencing of gene panels and mRNA expression profiling are now
      firmly established in clinical laboratories, in-depth proteome analysis has
      remained a niche technology, better suited for studying model systems rather than
      challenging materials such as clinical trial samples. To address this limitation,
      we have developed a novel and optimized platform called SP3-Clinical Tissue
      Proteomics (SP3-CTP) for in-depth proteome profiling of practical quantities of
      tumour tissues, including formalin fixed and paraffin embedded (FFPE). Using
      single 10 MUm scrolls of clinical tumour blocks, we performed in-depth
      quantitative analyses of individual sections from ovarian tumours covering the
      high-grade serous, clear cell, and endometrioid histotypes. This examination
      enabled the generation of a novel high-resolution proteome map of ovarian cancer
      histotypes from clinical tissues. Comparison of the obtained proteome data with
      large-scale genome and transcriptome analyses validated the observed proteome
      biology for previously validated hallmarks of this disease, and also identified
      novel protein features. A tissue microarray analysis validated cystathionine
      gamma-lyase (CTH) as a novel clear cell carcinoma feature with potential clinical
      relevance. In addition to providing a milestone in the understanding of ovarian
      cancer biology, these results show that in-depth proteomic analysis of clinically
      annotated FFPE materials can be effectively used as a biomarker discovery tool
      and perhaps ultimately as a diagnostic approach.

PMID- 27713571
TI  - HMG-CoAR expression in male breast cancer: relationship with hormone receptors,
      Hippo transducers and survival outcomes.
AB  - Male breast cancer (MBC) is a rare hormone-driven disease often associated with
      obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular
      route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR
      regulates the oncogenic Hippo transducers TAZ/YAP whose expression was previously
      associated with shorter survival in MBC. 225 MBC samples were immunostained for
      HMG-CoAR and 124 were considered eligible for exploring its relationship with
      hormone receptors (ER, PgR, AR), Hippo transducers and survival outcomes. HMG
      CoAR was positively associated with the expression of hormone receptors (ER, PgR,
      AR) and Hippo transducers. Overall survival was longer in patients with HMG-CoAR
      positive tumors compared with their negative counterparts (p = 0.031). Five- and
      10-year survival outcomes were better in patients whose tumors expressed HMG-CoAR
      (p = 0.044 and p = 0.043). Uni- and multivariate analyses for 10-year survival
      suggested that HMG-CoAR expression is a protective factor (HR 0.50, 95% CI: 0.25
      0.99, p = 0.048 and HR 0.53, 95% CI: 0.26-1.07, p = 0.078). Results were
      confirmed in a sensitivity analysis by excluding uncommon histotypes
      (multivariate Cox: HR 0.45, 95% CI: 0.21-0.97, p = 0.043). A positive
      relationship emerged between HMG-CoAR, hormone receptors and TAZ/YAP, suggesting
      a connection between the mevalonate pathway, the hormonal milieu and Hippo in
      MBC. Moreover, HMG-CoAR expression may be a favorable prognostic indicator.

PMID- 27713573
TI  - Tribological Properties of Water-lubricated Rubber Materials after Modification
      by MoS2 Nanoparticles.
AB  - Frictional vibration and noise caused by water-lubricated rubber stern tube
      bearings, which are generated under extreme conditions, severely threaten
      underwater vehicles' survivability and concealment performance. This study
      investigates the effect of flaky and spherical MoS2 nanoparticles on tribological
      properties and damping capacity of water-lubricated rubber materials, with the
      aim of decreasing frictional noise. A CBZ-1 tribo-tester was used to conduct the
      sliding tests between rubber ring-discs and ZCuSn10Zn2 ring-discs with water
      lubrication. These materials' typical mechanical properties were analysed and
      compared. Coefficients of friction (COFs), wear rates, and surface morphologies
      were evaluated. Frictional noise and critical velocities of generating friction
      vibration were examined to corroborate above analysis. Results showed that
      spherical MoS2 nanoparticles enhanced rubber material's mechanical and
      tribological properties and, in turn, reduced the friction noise and critical
      velocity. Flaky MoS2 nanoparticles reduced COF but did not enhance their
      mechanical properties, i.e., the damping capacity, wear resistance property;
      thus, these nanoparticles did not reduce the critical velocity obviously, even
      though increased the frictional noise at high load. The knowledge gained in the
      present work will be useful for optimizing friction pairs under extreme
      conditions to decrease frictional noise of water-lubricated rubber stern tube
      bearings.

PMID- 27713574
TI  - Structural insights into conformational stability of both wild-type and mutant
      EZH2 receptor.
AB  - Polycomb group (PcG) proteins have been observed to maintain the pattern of
      histone by methylation of the histone tail responsible for the gene expression in
      various cellular processes, of which enhancer of zeste homolog 2 (EZH2) acts as
      tumor suppressor. Overexpression of EZH2 results in hyper activation found in a
      variety of cancer. Point mutation on two important residues were induced and the
      results were compared between the wild type and mutant EZH2. The mutation of Y641
      and A677 present in the active region of the protein alters the interaction of
      the top ranked compound with the newly modeled binding groove of the SET domain,
      giving a GLIDE score of -12.26 kcal/mol, better than that of the wild type at 
      11.664 kcal/mol. In depth analysis were carried out for understanding the
      underlying molecular mechanism using techniques viz. molecular dynamics,
      principal component analysis, residue interaction network and free energy
      landscape analysis, which showed that the mutated residues changed the overall
      conformation of the system along with the residue-residue interaction network.
      The insight from this study could be of great relevance while designing new
      compounds for EZH2 enzyme inhibition and the effect of mutation on the overall
      binding mechanism of the system.

PMID- 27713572
TI  - Neuroprotective pentapeptide CN-105 improves functional and histological outcomes
      in a murine model of intracerebral hemorrhage.
AB  - Presently, no pharmacological treatments have been demonstrated to improve long
      term functional outcomes following intracerebral hemorrhage (ICH). Clinical
      evidence associates apolipoprotein E (apoE) genotype with ICH incidence and
      outcome. While apoE modifies neuroinflammatory responses through its adaptive
      role in glial downregulation, intact apoE holoprotein is too large to cross the
      blood-brain barrier (BBB). Therefore, we developed a 5-amino acid peptide - CN
      105 - that mimics the polar face of the apoE helical domain involved in receptor
      interactions. In the current study, we investigated the therapeutic potential of
      CN-105 in a mouse model of ICH. Three doses of CN-105 (0.05 mg/kg) was
      administered by tail vein injection within 24 hours after ICH induction.
      Functional assessment showed durable improvement in vestibulomotor performance
      after CN-105 treatment, as quantified by increased Rotarod latencies on Days 1-5
      post-ICH, and long-term improvement in neurocognitive performance, as quantified
      by reduced Morris water maze latencies on Days 29-32 post-ICH. Further, brain
      water content was significantly reduced, neuroinflammation was decreased and
      hippocampal CA3 neuronal survival was increased, although hemorrhage volume was
      not affected by CN-105. We concluded, therefore, that pentapeptide CN-105
      improved short- and long-term neurobehavioral outcomes in a murine model of ICH,
      suggesting therapeutic potential for patients with acute ICH.

PMID- 27713575
TI  - The efficacy of instrument assisted soft tissue mobilization: a systematic
      review.
AB  - BACKGROUND: Instrument assisted soft tissue mobilization (IASTM) is a popular
      treatment for myofascial restriction. IASTM uses specially designed instruments
      to provide a mobilizing effect to scar tissue and myofascial adhesions. Several
      IASTM tools and techniques are available such as the Graston(r) technique.
      Currently, there are no systematic reviews that have specifically appraised the
      effects of IASTM as a treatment or to enhance joint range of motion (ROM).
      PURPOSE: The purpose of this study was to systematically appraise the current
      evidence assessing the effects of IASTM as an intervention to treat a
      musculoskeletal pathology or to enhance joint ROM. METHODS: A search of the
      literature was conducted during the month of December 2015 which included the
      following databases: PubMed, PEDro, Science Direct, and the EBSCOhost collection.
      A direct search of known journals was also conducted to identify potential
      publications. The search terms included individual or a combination of the
      following: instrument; assisted; augmented; soft-tissue; mobilization;
      Graston(r); and technique. RESULTS: A total of 7 randomized controlled trials
      were appraised. Five of the studies measured an IASTM intervention versus a
      control or alternate intervention group for a musculoskeletal pathology. The
      results of the studies were insignificant (p>.05) with both groups displaying
      equal outcomes. Two studies measured an IASTM intervention versus a control or
      alternate intervention group on the effects of joint ROM. The IASTM intervention
      produced significant (P<.05) short term gains up to 24 hours. CONCLUSION: The
      literature measuring the effects of IASTM is still emerging. The current research
      has indicated insignificant results which challenges the efficacy of IASTM as a
      treatment for common musculoskeletal pathology, which may be due to the
      methodological variability among studies. There appears to be some evidence
      supporting its ability to increase short term joint ROM.

PMID- 27713577
TI  - A narrative review of new trends in the diagnosis of myofascial trigger points:
      diagnostic ultrasound imaging and biomarkers.
AB  - Myofascial pain syndrome (MPS) is one of the most common conditions of chronic
      musculoskeletal pain encountered by primary healthcare practitioners on a daily
      basis. It is generally accepted amongst the broad profile of healthcare
      practitioners treating MPS that the presence of discrete, palpable and tender
      nodules within the muscle, known as myofascial trigger points (MTrP), is
      necessary to confirm the diagnosis of MPS. Manual palpation is currently the most
      common technique used to detect MTrP, however, previous research has shown that
      the reliability of manual palpation for detecting MTrP is poor, and in our
      opinion unacceptably poor, leading to inconsistent diagnosis of MPS and poor
      patient outcomes. There are currently no objective accepted diagnostic criteria
      for the clinical detection of MTrP, nor are there standardized diagnostic
      criteria for MPS. Two promising areas of research with potential for enhancing
      the diagnosis of MPS include the use of diagnostic ultrasound and biomarkers.
      Further research is needed to advance the development of composite diagnostic
      criteria employing ultrasound imaging, biomarker assessments and physical
      assessment to enhance the accuracy and objectivity of MTrP detection and
      diagnosis of chronic MPS disorder.

PMID- 27713576
TI  - Neck pain in children: a retrospective case series.
AB  - INTRODUCTION: Spinal pain in the paediatric population is a significant health
      issue, with an increasing prevalence as they age. Paediatric patients attend for
      chiropractor care for spinal pain, yet, there is a paucity of quality evidence to
      guide the practitioner with respect to appropriate care planning. METHODS: A
      retrospective chart review was used to describe chiropractic management of
      paediatric neck pain. Two researchers abstracted data from 50 clinical files that
      met inclusion criteria from a general practice chiropractic office in the Greater
      Toronto Area, Canada. Data were entered into SPSS 15 and descriptively analyzed.
      RESULTS: Fifty paediatric neck pain patient files were analysed. Patients' age
      ranged between 6 and 18 years (mean 13 years). Most (98%) were diagnosed with
      Grade I-II mechanical neck pain. Treatment frequency averaged 5 visits over 19
      days; with spinal manipulative therapy used in 96% of patients. Significant
      improvement was recorded in 96% of the files. No adverse events were documented.
      CONCLUSION: Paediatric mechanical neck pain appears to be successfully managed by
      chiropractic care. Spinal manipulative therapy appears to benefit paediatric
      mechanical neck pain resulting from day-today activities with no reported serious
      adverse events. Results can be used to inform clinical trials assessing
      effectiveness of manual therapy in managing paediatric mechanical neck pain.

PMID- 27713578
TI  - A rare cause of chronic elbow pain in an adolescent baseball player: a case
      report.
AB  - OBJECTIVE: To present a case of chronic elbow pain as a result of a hidden
      underlying osteochondral defect. CLINICAL FEATURES: A 17-year old baseball player
      presented with chronic lateral elbow pain. Examination revealed swelling of the
      elbow with signs of possible ligament, muscle, and tendon injury. DIAGNOSIS AND
      TREATMENT: Although there was apparent soft-tissue injury, the elbow swelling
      created immediate suspicion of a more serious underlying condition. Examination
      revealed a swollen and tender elbow, with plain x-ray confirming a subchondral
      bone disorder (osteochondral defect) of the capitellum. Surgical repair was
      performed by an orthopedic surgeon using DeNovo NT Natural Tissue Grafts: the
      implantation of small pieces of juvenile joint cartilage into the affected area,
      using glue-like fibrin. Rehabilitation of the elbow began immediately following
      surgery. SUMMARY: Examination and imaging indicated that elbow pain in an
      adolescent baseball player could be from multiple sources, however, the chronic
      swelling raised suspicion of a condition requiring immediate and further
      investigation.

PMID- 27713579
TI  - Differences in hip range of motion among collegiate pitchers when compared to
      youth and professional baseball pitcher data.
AB  - The purpose of this study was to measure passive hip internal (IR) and external
      rotation (ER) range of motion (ROM) in collegiate baseball pitchers and compare
      to published youth and professional values. Measures were taken on the bilateral
      hips of 29 participants (mean age 20.0+/-1.4, range 18-22 years). Results
      identified no significant differences between the stance and stride hip in
      collegiate right handed pitchers for IR (p= 0.22, ES 0.23) and ER (p=.08, ES=
      0.25). There was no significant difference in left handed pitchers for IR (p=
      0.80, ES= 0.11) and ER (p= 0.56, ES= 0.15). When comparing youth to collegiate,
      IR increased in the stance (2o) and stride (5o) hip and an increase in the stance
      (5o) and stride (5o) hip were present for ER as well. From collegiate to
      professional, IR increased in the stance (4o) and stride (3o) hip whereas a
      decrease in the stance (9o) and stride (12o) hip was present for ER. The data
      suggests an increase in passive ROM from youth to collegiate and a decrease from
      collegiate to professional. Understanding passive hip ROM values among the
      different levels of pitchers may assist clinicians in developing time dependent
      interventions to prevent future injury and enhance performance.

PMID- 27713580
TI  - The meaning of it all: evaluating knowledge of Minimal Clinically Important
      Difference (MCID) among chiropractic students.
AB  - INTRODUCTION: Patient-reported outcome measures are frequently used to monitor
      patient progress during chiropractic care, yet student interns utilizing such
      assessments are unfamiliar with what magnitude of change (MCID) is considered
      beneficial to the patient. OBJECTIVE: This work seeks to determine chiropractic
      intern knowledge of MCID. METHODS: A five-item survey was administered to 104
      chiropractic student interns. RESULTS: Nearly one-third of the interns correctly
      defined the MCID acronym, and approximately one-third of the interns knew at
      least one MCID value for the outcome assessments in the EHR. Surprisingly, 20% of
      the interns reported knowledge of at least one MCID value, but answered
      incorrectly pertaining to the MCID acronym. CONCLUSION: Student interns value
      patient perception, but have limited knowledge of MCID values. Addressing this
      gap will improve their understanding of patient progress and inform their
      treatment decisions both in the outpatient clinic and in their practices
      following graduation.

PMID- 27713582
TI  - Imaging case reviews.

PMID- 27713581
TI  - Multiple seizure-induced thoracic vertebral compression fractures: a case report.
AB  - BACKGROUND: Musculoskeletal injuries stemming from forceful muscular contractions
      during seizures have been documented in the literature. Reports of multiple
      seizure-induced spinal fractures, in the absence of external trauma and without
      risk factors for fracture, are rare. CASE PRESENTATION: A 28-year-old male, newly
      diagnosed with epilepsy, presented to a chiropractic clinic with the complaint of
      mid-thoracic pain beginning after a tonic-clonic seizure with no associated
      external trauma. Radiographs revealed the impression of five new vertebral
      compression fractures from T4 to T8. DISCUSSION: This report highlights the
      importance of a complete history and examination of patients with a history of
      tonic-clonic seizures and back pain, especially when considering spinal
      adjustments. SUMMARY: This case report presents an argument that a tonic-clonic
      seizure, in the absence of external trauma or significant risk factors for
      fracture, resulted in multiple vertebral compression fractures.

PMID- 27713583
TI  - Advanced hip joint degeneration associated with femoroacetabular impingement in a
      retired chiropractor.
AB  - Femoroacetabular impingement is a relatively new clinical entity only recently
      described in the orthopedic literature. In this report, we document a severe case
      of hip joint osteoarthritis associated with cam-type impingement in a retired
      chiropractor.

PMID- 27713584
TI  - Sciatic neuralgia associated with a perineural (Tarlov) cyst.
AB  - Perineural (Tarlov) cysts are rare and are usually asymptomatic and an incidental
      finding on routine spinal imaging. Presented here is a case of sciatic neuralgia
      in a 56-year-old patient whose clinical symptoms correlated with a lower lumbar
      perineural cyst.

PMID- 27713585
TI  - Analyzing Single Giant Unilamellar Vesicles With a Slotline-Based RF Nanometer
      Sensor.
AB  - Novel techniques that enable reagent free detection and analysis of single cells
      are of great interest for the development of biological and medical sciences as
      well as point-of-care health service technologies. Highly sensitive and broadband
      radio-frequency (RF) sensors are promising candidates for such a technique. In
      this work, we present a highly sensitive and tunable RF sensor, which is based on
      interference processes and built with a 100 nm slotline structure. The highly
      concentrated RF fields, up to ~1.76*107 V/m, enable strong interactions between
      Giant unilamellar vesicles (GUVs) and fields for high sensitivity operations. We
      also provide two modeling approaches to extract cell dielectric properties from
      measured scattering parameters. GUVs of different molecular compositions are
      synthesized and analyzed with the RF sensor at ~2 GHz, ~2.5 GHz, and ~2.8 GHz
      with an initial |S21 | min of ~-100 dB. Corresponding GUV dielectric properties
      are obtained. A one-dimensional scanning of single GUV is also demonstrated.

PMID- 27713586
TI  - ?Educacion o desintegracion? Parental migration, remittances and left-behind
      children's education in western Guatemala.
AB  - A growing body of literature addresses the positive impacts of international
      migration and remittances on children's education. This paper offers a nuanced,
      qualitative view that addresses the positive remittance-related benefits to
      children's education and the negative repercussions of parental absences on
      children's relationships with schooling from the perspectives of parents and
      local educators. A case study approach including field interviews of parents,
      teachers and school administrators from five western Guatemalan communities was
      used. Findings suggest that remittances improve basic living conditions, allowing
      many children to access a more comfortable and substantive education. However,
      parental absences can disrupt the educational opportunities for others.

PMID- 27713587
TI  - Priming effect of benthic gastropod mucus on sedimentary organic matter
      remineralization.
AB  - Mucous gels are produced by benthic animals rapidly and in copious amounts, and
      consequently they are a possible priming substrate whose addition in modest
      amounts may affect sedimentary organic matter (SOM) remineralization. The priming
      effect of benthic infaunal mucus was tested using mucus of the common gastropod
      Neverita duplicata as model substrate. Its composition is typical of marine
      molluscan mucus, consisting primarily of water (>96% by weight). Salt-free dry
      weight constitutes 0.7% of total mucus. Relationships between C, N and S content
      show the presence of N-free and S-free fractions, indicative of
      mucopolysaccharides, that account for approximately half of the total C present.
      The C/N ratios of the N-containing fraction (6.1 and 8.75 for pedal and
      hypobranchial mucus, respectively) are indicative of a carbohydrate-protein
      complex. Relatively low C/S ratios for the S-containing fraction (21.8 and 10.5
      for pedal and hypobranchial mucus, respectively) and positive staining with
      Alcian Blue dye are indicative of S-ester and alkyl-SO42- groups bridging
      mucopolysaccharide and glycoprotein components. Anaerobic incubations of pedal
      mucus, sediment and mucus-sediment mixture resulted in the generation of SigmaCO2
      and NH4+ at ratios lower than substrate C/N ratios, indicating the preferential
      decomposition of N-rich components. Production rates of SigmaCO2 and NH4+ in
      mucus-sediment incubations are higher, by 9+/-16% and 29+/-11%, respectively,
      than those predicted from linear addition of mucus-only and sediment-only rates.
      The accelerated remineralization rate of N in the presence of modest mucus
      contribution suggests that benthic mucus addition can affect SOM remineralization
      processes through a "priming" effect.

PMID- 27713588
TI  - Acceleration of metallacycle-mediated alkyne-alkyne cross-coupling with TMSCl.
AB  - Investigation of titanium-centered metallacycle-mediated cross-coupling between
      unsymmetrical internal alkynes has led to the discovery that TMSCl significantly
      accelerates the C-C bond forming event. We report a collection of results that
      compare the efficiency of this reaction employing Ti(Oi-Pr)4/2n-BuLi in PhMe with
      and without TMSCl, demonstrating in every case that the presence of TMSCl has a
      profound impact on efficiency. While relevant in the context of developing this
      fundamental bond-forming process as an entry to more complex organometallic
      transformations, these modified reaction conditions allow coupling processes to
      be run at > 10 times the concentrations previously possible [in 2.4M n-BuLi
      (hexanes)], without the requirement of additional solvent. Finally, we
      demonstrate the effectiveness of these modified reaction conditions for the
      annulative cross-coupling between TMS-alkynes and 1,6-enynes leading to the
      formation of angularly substituted hydrindanes with, now well appreciated, high
      levels of regio- and stereoselection.

PMID- 27713590
TI  - Spatio-Temporal EEG Models for Brain Interfaces.
AB  - Multichannel electroencephalography (EEG) is widely used in non-invasive brain
      computer interfaces (BCIs) for user intent inference. EEG can be assumed to be a
      Gaussian process with unknown mean and autocovariance, and the estimation of
      parameters is required for BCI inference. However, the relatively high
      dimensionality of the EEG feature vectors with respect to the number of labeled
      observations lead to rank deficient covariance matrix estimates. In this
      manuscript, to overcome ill-conditioned covariance estimation, we propose a
      structure for the covariance matrices of the multichannel EEG signals.
      Specifically, we assume that these covariances can be modeled as a Kronecker
      product of temporal and spatial covariances. Our results over the experimental
      data collected from the users of a letter-by-letter typing BCI show that with
      less number of parameter estimations, the system can achieve higher
      classification accuracies compared to a method that uses full unstructured
      covariance estimation. Moreover, in order to illustrate that the proposed
      Kronecker product structure could enable shortening the BCI calibration data
      collection sessions, using Cramer-Rao bound analysis on simulated data, we
      demonstrate that a model with structured covariance matrices will achieve the
      same estimation error as a model with no covariance structure using fewer labeled
      EEG observations.

PMID- 27713589
TI  - Replacement of the Bryostatin A- and B-Pyran Rings With Phenyl Rings Leads to
      Loss of High Affinity Binding With PKC.
AB  - We describe a convergent synthesis of a bryostatin analogue in which the natural
      A- and B-ring pyrans have been replaced by phenyl rings. The new analogue
      exhibited PMA like behavior in cell assays, but failed to maintain high affinity
      binding for PKC, despite retaining an unaltered C-ring 'binding domain'.

PMID- 27713591
TI  - Inter- and intra-specific variation in drought sensitivity in Abies spec. and its
      relation to wood density and growth traits.
AB  - Understanding drought sensitivity of tree species and its intra-specific
      variation is required to estimate the effects of climate change on forest
      productivity, carbon sequestration and tree mortality as well as to develop
      adaptive forest management measures. Here, we studied the variation of drought
      reaction of six European Abies species and ten provenances of Abies alba planted
      in the drought prone eastern Austria. Tree-ring and X-ray densitometry data were
      used to generate early- and latewood measures for ring width and wood density.
      Moreover, the drought reaction of species and provenances within six distinct
      drought events between 1970 and 2011, as identified by the standardized
      precipitation index, was determined by four drought response measures. The mean
      reaction of species and provenances to drought events was strongly affected by
      the seasonal occurrence of the drought: a short, strong drought at the beginning
      of the growing season resulted in growth reductions up to 50%, while droughts at
      the end of the growing season did not affect annual increment. Wood properties
      and drought response measures showed significant variation among Abies species as
      well as among A. alba provenances. Whereas A. alba provenances explained
      significant parts in the variation of ring width measures, the Abies species
      explained significant parts in the variation of wood density parameters. A
      consistent pattern in drought response across the six drought events was observed
      only at the inter-specific level, where A. nordmanniana showed the highest
      resistance and A. cephalonica showed the best recovery after drought. In
      contrast, differences in drought reaction among provenances were only found for
      the milder drought events in 1986, 1990, 1993 and 2000 and the ranking of
      provenances varied at each drought event. This indicates that genetic variation
      in drought response within A. alba is more limited than among Abies species. Low
      correlations between wood density parameters and drought response measures
      suggest that wood density is a poor predictor of drought sensitivity in Abies
      spec.

PMID- 27713592
TI  - Deposition, Heat Treatment And Characterization of Two Layer Bioactive Coatings
      on Cylindrical PEEK.
AB  - Polyether ether ketone (PEEK) rods were coated via ion beam asssited deposition
      (IBAD) at room temperature. The coating consists of a two-layer design of yttria
      stabilized zirconia (YSZ) as a heat-protection layer, and hydroxyapatite (HA) as
      a top layer to increase bioactivity. A rotating substrate holder was designed to
      deposit an even coating on the cylindrical surface of PEEK rods; the uniformity
      is verified by cross-sectional measurements using scanning electron microscopy
      (SEM). Deposition is followed by heat treatment of the coating using microwave
      annealing and autoclaving. Transmission electron microscopy (TEM) showed a dense,
      uniform columnar grain structure in the YSZ layer that is well bonded to the PEEK
      substrate, while the calcium phosphate layer was amorphous and pore-free in its
      as-deposited state. Subsequent heat treatment via microwave energy introduced HA
      crystallization in the calcium phosphate layer and additional autoclaving further
      expanded the crystallization of the HA layer. Chemical composition evaluation of
      the coating indicated the Ca/P ratios of the HA layer to be near that of
      stoichiometric HA, with minor variations through the HA layer thickness. The
      adhesion strength of as-deposited HA/YSZ coatings on smooth, polished PEEK
      surfaces was mostly unaffected by microwave heat treatment, but decreased with
      additional autoclave treatment. Increasing surface roughness showed improvement
      of bond strength.

PMID- 27713593
TI  - Multiple Imputation of a Randomly Censored Covariate Improves Logistic Regression
      Analysis.
AB  - Randomly censored covariates arise frequently in epidemiologic studies. The most
      commonly used methods, including complete case and single imputation or
      substitution, suffer from inefficiency and bias. They make strong parametric
      assumptions or they consider limit of detection censoring only. We employ
      multiple imputation, in conjunction with semi-parametric modeling of the censored
      covariate, to overcome these shortcomings and to facilitate robust estimation. We
      develop a multiple imputation approach for randomly censored covariates within
      the framework of a logistic regression model. We use the non-parametric estimate
      of the covariate distribution or the semiparametric Cox model estimate in the
      presence of additional covariates in the model. We evaluate this procedure in
      simulations, and compare its operating characteristics to those from the complete
      case analysis and a survival regression approach. We apply the procedures to an
      Alzheimer's study of the association between amyloid positivity and maternal age
      of onset of dementia. Multiple imputation achieves lower standard errors and
      higher power than the complete case approach under heavy and moderate censoring
      and is comparable under light censoring. The survival regression approach
      achieves the highest power among all procedures, but does not produce
      interpretable estimates of association. Multiple imputation offers a favorable
      alternative to complete case analysis and ad hoc substitution methods in the
      presence of randomly censored covariates within the framework of logistic
      regression.

PMID- 27713594
TI  - Environmental Perceptions and Health before and after Relocation to a Green
      Building.
AB  - Green buildings are designed to have low environmental impacts and improved
      occupant health and well-being. Improvements to the built environment including
      ventilation, lighting, and materials have resulted in improved indoor
      environmental quality (IEQ) in green buildings, but the evidence around occupant
      health is currently centered around environmental perceptions and self-reported
      health. To investigate the objective impact of green buildings on health, we
      tracked IEQ, self-reported health, and heart rate in 30 participants from green
      and conventional buildings for two weeks. 24 participants were then selected to
      be relocated to the Syracuse Center of Excellence, a LEED platinum building, for
      six workdays. While they were there, ventilation, CO2, and volatile organic
      compound (VOC) levels were changed on different days to match the IEQ of
      conventional, green, and green+ (green with increased ventilation) buildings.
      Participants reported improved air quality, odors, thermal comfort, ergonomics,
      noise and lighting and fewer health symptoms in green buildings prior to
      relocation. After relocation, participants consistently reported fewer symptoms
      during the green building conditions compared to the conventional one, yet
      symptom counts were more closely associated with environmental perceptions than
      with measured IEQ. On average, participants had 4.7 times the odds of reporting a
      lack of air movement, 1.4 more symptoms (p-value = 0.019) and a 2 bpm higher
      heart rate (p-value < 0.001) for a 1000 ppm increase in indoor CO2 concentration.
      These findings suggest that occupant health in green and conventional buildings
      is driven by both environmental perceptions and physiological pathways.

PMID- 27713595
TI  - Eurytemora carolleeae in the Laurentian Great Lakes revealed by phylogenetic and
      morphological analysis.
AB  - In the Laurentian Great Lakes, specimens of Eurytemora have been reported as E.
      affinis since its invasion in the late 1950s. During an intensive collection of
      aquatic invertebrates for morphological and molecular identification in Western
      Lake Erie in 2012-2013, several specimens of Eurytemora were collected. Analysis
      of these specimens identified them as the recently described species E.
      carolleeae Alekseev and Souissi 2011. This result led us to assess E.
      carolleeae's identifying features, geographic distribution and historical
      presence in the Laurentian Great Lakes in view of its recent description in 2011.
      Cytochrome oxidase I (COI) DNA sequences of Eurytemora specimens were identified
      as closer (2 - 4% different) to recently described E. carolleeae than to most
      Eurytemora affinis sequences (14% different). Eurytemora from other areas of the
      Great Lakes and from North American rivers as far west as South Dakota (Missouri
      River) and east to Delaware (Christina River) also keyed to E. carolleeae.
      Morphological analysis of archival specimens from 1962 and from all the Great
      Lakes were identified as E. carolleeae. Additionally, Eurytemora drawings in
      previous publications from studies in the Holarctic region were reassessed to
      determine if these specimens were E. carolleeae. Additional morphological
      characters that may distinguish the North American E. carolleeae from other taxa
      are also described. We conclude that E. carolleeae is the correct name for the
      species of Eurytemora that has inhabited the Great Lakes since its invasion, as
      established by both morphological and COI sequence comparisons to reference keys
      and sequence databases in present and archival specimens.

PMID- 27713596
TI  - [Focus on RNA polymerase II].

PMID- 27713597
TI  - Sexual Orientation, Race, and Trauma as Predictors of Sexual Assault Recovery.
AB  - Sexual minorities and racial minorities experience greater negative impact
      following sexual assault. We examined recovery from sexual assault among women
      who identified as heterosexual and bisexual across racial groups. A community
      sample of women (N = 905) completed three yearly surveys about sexual
      victimization, recovery outcomes, race group, and sexual minority status.
      Bisexual women and Black women reported greater recovery problems. However, Black
      women improved more quickly on depression symptoms than non-Black women. Finally,
      repeated adult victimization uniquely undermined survivors' recovery, even when
      controlling for child sexual abuse. Sexual minority and race status variables and
      their intersections with revictimization play roles in recovery and should be
      considered in treatment protocols for sexual assault survivors.

PMID- 27713599
TI  - Influence of tree shape and evolutionary time-scale on phylogenetic diversity
      metrics.
AB  - During the last decades, describing, analysing and understanding the phylogenetic
      structure of species assemblages has been a central theme in both community
      ecology and macro-ecology. Among the wide variety of phylogenetic structure
      metrics, three have been predominant in the literature: Faith's phylogenetic
      diversity (PDFaith), which represents the sum of the branch lengths of the
      phylogenetic tree linking all species of a particular assemblage, the mean
      pairwise distance between all species in an assemblage (MPD) and the pairwise
      distance between the closest relatives in an assemblage (MNTD). Comparisons
      between studies using one or several of these metrics are difficult because there
      has been no comprehensive evaluation of the phylogenetic properties each metric
      captures. In particular it is unknown how PDFaith relates to MDP and MNTD.
      Consequently, it is possible that apparently opposing patterns in different
      studies might simply reflect differences in metric properties. Here, we aim to
      fill this gap by comparing these metrics using simulations and empirical data. We
      first used simulation experiments to test the influence of community structure
      and size on the mismatch between metrics whilst varying the shape and size of the
      phylogenetic tree of the species pool. Second we investigated the mismatch
      between metrics for two empirical datasets (gut microbes and global carnivoran
      assemblages). We show that MNTD and PDFaith provide similar information on
      phylogenetic structure, and respond similarly to variation in species richness
      and assemblage structure. However, MPD demonstrate a very different behaviour,
      and is highly sensitive to deep branching structure. We suggest that by combining
      complementary metrics that are sensitive to processes operating at different
      phylogenetic depths (i.e. MPD and MNTD or PDFaith) we can obtain a better
      understanding of assemblage structure.

PMID- 27713598
TI  - Shape Control of Colloidal Cu2-x S Polyhedral Nanocrystals by Tuning the
      Nucleation Rates.
AB  - Synthesis protocols for colloidal nanocrystals (NCs) with narrow size and shape
      distributions are of particular interest for the successful implementation of
      these nanocrystals into devices. Moreover, the preparation of NCs with well
      defined crystal phases is of key importance. In this work, we show that Sn(IV)
      thiolate complexes formed in situ strongly influence the nucleation and growth
      rates of colloidal Cu2-x S polyhedral NCs, thereby dictating their final size,
      shape, and crystal structure. This allowed us to successfully synthesize
      hexagonal bifrustums and hexagonal bipyramid NCs with low-chalcocite crystal
      structure, and hexagonal nanoplatelets with various thicknesses and aspect ratios
      with the djurleite crystal structure, by solely varying the concentration of
      Sn(IV)-additives (namely, SnBr4) in the reaction medium. Solution and solid-state
      119Sn NMR measurements show that SnBr4 is converted in situ to Sn(IV)-thiolate
      complexes, which increase the Cu2-x S nucleation barrier without affecting the
      precursor conversion rates. This influences both the nucleation and growth rates
      in a concentration-dependent fashion and leads to a better separation between
      nucleation and growth. Our approach of tuning the nucleation and growth rates
      with in situ-generated Sn-thiolate complexes might have a more general impact due
      to the availability of various metal-thiolate complexes, possibly resulting in
      polyhedral NCs of a wide variety of metal-sulfide compositions.

PMID- 27713600
TI  - Association of Single Nucleotide Polymorphisms with Atrial Fibrillation and the
      Outcome after Catheter Ablation.
AB  - BACKGROUND: The association of gene variants with atrial fibrillation (AF) type
      and the recurrence of AF after catheter ablation in Taiwan is still unclear. In
      this study, we aimed to investigate the relationships between gene variants, AF
      type, and the recurrence of AF. METHODS: In our investigation, we examined 383
      consecutive patients with AF (61.9 +/- 14.0 years; 63% men); of these 383
      patients, 189 underwent catheter ablation for drug-refractory AF. Thereafter, the
      single nucleotide polymorphisms rs2200733, and rs7193343 were genotyped using
      real-time polymerase chain reaction. RESULTS: The rs7193343 variant was
      independently associated with non-paroxysmal AF (non-PAF). In the PAF group, the
      rs7193343 variant was independently associated with AF recurrence after catheter
      ablation. However, the rs2200733 variant was not associated with AF recurrence in
      this group. The combination of the rs7193343 and rs2200733 risk alleles was
      associated with a better predictive power in the PAF patients. In contrast, in
      the non-PAF group, the SNPs were not associated with recurrence. The rs7193343
      and rs2200733 variants were not associated with different atrial voltage and
      activation times. CONCLUSIONS: The rs7193343 variants were associated with AF
      recurrence after catheter ablation in PAF patients but not in non-PAF patients.
      The rs7193343 CC variant was independently associated with non-PAF.

PMID- 27713601
TI  - Elevated Neutrophil-to-Lymphocyte Ratio Predicts Intermediate-Term Outcomes in
      Patients Who Have Advanced Chronic Kidney Disease with Peripheral Artery Disease
      Receiving Percutaneous Transluminal Angioplasty.
AB  - BACKGROUND: Inflammation plays an important role in the pathogenesis of
      cardiovascular disease in patients with advanced chronic kidney disease (CKD).
      Neutrophil-to-lymphocyte ratio (NLR), an inflammatory biomarker, has not been
      evaluated in patients who have advanced CKD with peripheral artery disease (PAD)
      undergoing percutaneous transluminal angioplasty (PTA), especially in Taiwan.
      METHODS: We retrospectively evaluated 148 advanced CKD (creatinine clearance rate
      <= 30 mL/min/1.73 m2) identified from a prospective registry in our hospital (303
      PTA cases in total). Kaplan-Meier analysis with log-rank test was used to study
      event-free survival, and all univariables (p value < 0.1) were put into
      multivariate Cox regression analysis. RESULTS: During the mean follow-up time of
      8.6 +/- 7.8 months, 35.1% of the cases achieved primary composite endpoint (all
      cause mortality or major amputation), 25.5% underwent death from any cause, and
      14.9% underwent major or minor amputation. Rutherford grade 6, either NLR or NLR
      >= 3.76, and a history of hypertension had a positively prognostic impact on the
      occurrence of primary composite endpoint, whereas higher albumin level (>= 3.0
      mg/dL) and technical success had a significantly protective effect. History of
      hypertension, either NLR or NLR >= 3.76, and age were associated with all-cause
      mortality. In addition, Rutherford 6, higher albumin level (>= 3.0 mg/dL),
      technical success, NLR, and age could predict the occurrence of major amputation.
      CONCLUSIONS: NLR, but not C-reactive protein or platelet-lymphocyte ratio, is an
      important prognostic predictor of all major clinical outcomes in patients with
      advanced CKD and PAD receiving PTA. Further studies are warranted to establish a
      better strategy and healthcare program in this clinical setting.

PMID- 27713602
TI  - Increased Platelet-to-Lymphocyte Ratios and Low Relative Lymphocyte Counts
      Predict Appropriate Shocks in Heart Failure Patients with ICDs.
AB  - BACKGROUND: Platelet-to-lymphocyte ratio (PLR) and relative lymphocyte count (L%)
      are commonly available tests that can be obtained from complete blood count. The
      aim of this study was to investigate the association between appropriate
      defibrillator therapy and PLR, and whether decreased lymphocyte count may predict
      appropriate implantable cardioverter defibrillator (ICD) shocks in heart failure
      (HF) patients. METHODS: A total of 147 patients with ischemic or non-ischemic HF
      who underwent ICD implantation for primary prevention were enrolled in this
      study. Peripheral venous blood samples were drawn on the same day as ICD
      implantation. White blood cell counts with differentials, red blood cell indices,
      and platelet counts were calculated with an automated blood cell counter. All
      patients were evaluated according to the presence of appropriate ICD therapy.
      RESULTS: Baseline ejection fraction was significantly lower in the appropriate
      shock received group (p = 0.040). Median PLR was significantly higher and L% was
      significantly lower in the appropriate shock received group (p < 0.001). In both
      ischemic and non-ischemic HF groups, median L% was significantly lower in the
      appropriate shock received group (p < 0.001; p = 0.006, respectively). In
      multivariable logistic regression analysis, only L% showed a strong association
      with appropriate shock therapy (p < 0.001). CONCLUSIONS: Higher PLRs are related
      to appropriate shocks in patients that received ICD with lower EF. Furthermore,
      decreased L% is independently associated with appropriate shocks in HF.

PMID- 27713603
TI  - The Early Predictive Value of Right Ventricular Strain in Epirubicin-Induced
      Cardiotoxicity in Patients with Breast Cancer.
AB  - BACKGROUND: As cancer therapies have improved, patient life spans have been
      extended but quality of life has been threatened by chemotherapy induced
      cardiotoxicity. Most cardiac complications remain unobserved until specific
      symptoms develop. Speckle-tracking echocardiography is a sensitive imaging
      modality in detecting early occult myocardial dysfunction. METHODS: A total
      number of 35 patients newly diagnosed with breast cancer and preparing for
      epirubicin therapy were prospectively recruited. Echocardiography, including
      speckle-tracking echocardiography, was performed sequentially at baseline (T1),
      after the first cycle (T2) and after the third cycle (T3) of epirubicin. At each
      visit, the severity of dyspnea was evaluated by the assessment scale. RESULTS:
      Compared with the baseline, right ventricular longitudinal strain (RVLS_FW) at T2
      significantly declined (-22.49 +/- 4.97 vs. -18.48 +/- 4.46, p = 0.001), which
      was also positively associated with the development of dyspnea (R2 = 0.8, p =
      0.01). At T3, both the left ventricular global longitudinal strain and RVLS_FW
      were significantly impaired (-21.4 +/- 4.12 vs. -16.94 +/- 6.81%; -22.49 +/- 4.97
      vs. -16.86 +/- 7.27%, p = 0.01; 0.001, respectively). Also, the accumulating dose
      of epirubicin positively correlated with the development of dyspnea (R2 = 0.38, p
      = 0.04) and the decline of RVLS_FW (R2 = 0.53, p = 0.02). Notably, compared with
      the other echocardiographic parameters only RVLS_FW at the early stage (T2)
      significantly correlated with the development of dyspnea (odds ratio: 1.84, 95%
      confidence interval: 1.22-2.78, p = 0.04). CONCLUSIONS: RVLS_FW sensitively
      predicts dyspnea development in breast cancer patients receiving epirubicin
      therapy. However, larger scale studies are required to validate its role in long
      term patient survival.

PMID- 27713604
TI  - Echocardiography for Evaluation of Oncology Therapy-Related Cardiotoxicity.

PMID- 27713605
TI  - Impact of Statins Therapy for Ischemic Heart Disease Patients with Low-Density
      Lipoprotein Cholesterol Levels Less Than 100 mg/dL.
AB  - BACKGROUND: The objective of this study was to determine whether the use of
      statins prevents the progression of ischemic heart disease (IHD) in patients with
      low levels of low-density lipoprotein cholesterol (LDL-C). METHODS: We reviewed
      data obtained from IHD patients who underwent first percutaneous coronary
      intervention (PCI). Patients underwent follow-up coronary angiography (re-CAG)
      after PCI. However, only patients with LDL-C levels less than 100 mg/dL at PCI
      were included in this study. Ultimately, 92 patients were enrolled. All patients
      were divided into two groups: 1) patients who were treated with statins (n = 69),
      and 2) patients who were not treated with statins (n = 23). RESULTS: The two
      groups had similar LDL-C levels at PCI. At re-CAG, the ratio of patients who
      underwent PCI for de novo lesion in the statin group was lower than that in the
      non-statin group (12% vs. 48%) (p < 0.001). In multiple regression analysis,
      statin usage and LDL-C level at PCI were independent predictors of the ratio of
      patients undergoing PCI for de novo lesion. CONCLUSIONS: Statins therapy for
      patients whose LDL-C levels are less than 100 mg/dL has a beneficial effect on
      secondary prevention of IHD.

PMID- 27713606
TI  - Frequency of Vascular Inflammation and Impact on Neointimal Proliferation of Drug
      Eluting Stents in Porcine Coronary Arteries.
AB  - BACKGROUND: We aimed to describe the frequency of vascular inflammatory reactions
      with second generation drug eluting stents (DES) compared to first generation
      DES, and analyze the impact on inflammation and neointimal proliferation in a
      porcine coronary model. METHODS: A total of 26 stents (7 multi-link VISION, 6
      CYPHER, 6 TAXUS and 7 XIENCE V) were deployed in the coronary arteries of 10
      domestic swine for 28 days, after which each stent was harvested and processed
      (divided into 8 or 9 segments) for histomorphometric analysis. RESULTS: A total
      of 202 histological segments [146 DES and 56 bare metal stents (BMS)] were
      included in this study. The mean neointimal thickness was significantly reduced
      in the DES group compared to the BMS group. The DES group had higher injury
      scores (DES = 0.99 +/- 0.79 versus BMS = 0.67 +/- 0.44, p < 0.004), inflammatory
      scores (DES = 2.09 +/- 1.54 versus BMS = 0.64 +/- 0.98, p < 0.001) and presence
      of para-strut granulomas (DES = 35% versus BMS = 2%, p < 0.001). In logistic
      regression analysis, the presence of para-strut granulomas correlated with an
      area of stenosis > 50% (RR: 6.11, 95% CI: 2.97 to 12.59, p = 0.001). In the DES
      group, the second generation stents had a lower neointimal area (XIENCE V: 1.64
      +/- 0.90 mm2) compared to the first generation stents (TAXUS: 2.36 +/- 1.56 mm2,
      p = 0.005; CYPHER 2.78 +/- 1.82 mm2, p = 0.001). The XIENCE V stents had lower
      inflammatory scores and lower frequency of para-strut granulomas compared to the
      first generation stents. CONCLUSIONS: Second generation DES had a lower incidence
      of vascular inflammatory reactions compared to first generation DES. This
      biological phenomenon appears to influence the patterns of neointimal formation.

PMID- 27713607
TI  - Impact of Atorvastatin Combined with Ezetimibe for the Treatment of Carotid
      Atherosclerosis in Patients with Coronary Heart Disease.
AB  - BACKGROUND: This study aimed to investigate the impact of atorvastatin (Ato)
      combined with ezetimibe (Eze) for the treatment of carotid atherosclerosis in
      patients with coronary heart disease (CHD). METHODS: One hundred and forty-eight
      CHD patients with carotid atherosclerosis were divided into the control (Ato
      alone) and combination (Ato and Eze) groups. The treatment course was 12 months;
      patient blood lipids, carotid intima-media thickness (CIMT), and carotid plaque
      area were measured before and after treatment. RESULTS: Twelve months after
      treatment, there was a decrease in the CIMT, and the horizontal and vertical axes
      of the carotid plaque areas in both groups, compared to pretreatment values. The
      serum low-density lipoprotein cholesterol (LDL-C) levels were significantly
      decreased (p < 0.05). There were statistically significant differences (p < 0.05)
      in the LDL-C (2.12 +/- 0.58 mmol/L vs. 2.63 +/- 0.56 mmol/L) and CIMT (1.06 +/-
      0.12 mm vs. 1.13 +/- 0.11 mm) levels between the combination and the control
      groups after treatment. Compared to the control group, the horizontal (0.18 +/-
      0.06 cm2 vs. 0.19 +/- 0.05 cm2) and vertical carotid arterial plaque areas (0.40
      +/- 0.15 cm2 vs. 0.41 +/- 0.17 cm2) of the combination group were reduced after
      treatment. However, the difference was not statistically significant (p > 0.05).
      CONCLUSIONS: The combination of Ato and Eze further reduces LDL-C levels and
      CIMT, and affect the progression of carotid atherosclerosis in CHD patients with
      hypercholesterolemia.

PMID- 27713608
TI  - Aliskiren Inhibits Neointimal Matrix Metalloproteinases in Experimental
      Atherosclerosis.
AB  - BACKGROUND: The renin-angiotensin system (RAS) plays an important role in
      atherosclerosis. Acting via the angiotensin II receptor, type 1, oxidative stress
      increases and contributes to endothelial dysfunction and vascular inflammation.
      Renin exerts effects through a renin receptor causing an increase in the
      efficiency of angiotensinogen cleavage and facilitates angiotensin II (Ang II)
      generation and action on cell surfaces. Ang II enhances proliferation and
      migration of vascular smooth muscle cells, indicating a direct involvement of the
      RAS in smooth muscle cell proliferation during neointimal formation. Aliskiren, a
      direct renin inhibitor, is a new oral antihypertensive drug. However, the role of
      the direct renin inhibitor in neointimal formation and vascular matrix
      metalloproteinases remains unclear. METHODS: To investigate the effects of
      aliskiren on the expression of vascular matrix metalloproteinases, we evaluated
      the aortic neointimal formation of high-cholesterol-fed animals after vascular
      injury in vivo and the cellular function of the tumor necrosis factor-alpha
      stimulated human aortic smooth muscle cells in vitro. Thereafter, we evaluated
      vascular expression (by western blot), activity (by gelatin zymography) and
      molecular pathway. RESULTS: In this study we demonstrated that aliskiren reduced
      neointimal hyperplasia in hypercholesterolemic rabbits after vascular injury and
      the expression of matrix metalloproteinases in the neointima. Aliskiren also
      inhibited the expression and activities of matrix metalloproteinases on tumor
      necrosis factor-alpha (TNF-alpha)-stimulated human aortic smooth muscle cells via
      the mitogen-activated protein kinase pathway. CONCLUSIONS: The present study
      showed that aliskiren inhibited the expression of vascular matrix
      metalloproteinases. With these results, we have better clarified the potential
      role of renin inhibitors in human atherosclerosis.

PMID- 27713609
TI  - Secondhand Smoke Exposure Enhances Cardiac Fibrosis Effects on the Aging Rat
      Hearts.
AB  - BACKGROUND: Examining aging rats exposed to secondhand smoke (SHS) engenders
      changes in left ventricular remodeling due to age- or disease-dependent
      alterations. METHODS: Rats were placed in whole-body exposure chambers and
      exposed to 10 cigarettes. Filtered air was introduced into the chamber at a low
      rate. Rats were exposed to SHS for 30 min, twice a day, 5 days per week for 1
      month. After 4 weeks SHS exposure, rats were sacrificed for morphological study
      with trichome staining and left ventricular remodeling related protein analysis
      using western blot. RESULTS: Characteristic fibrotic morphology in the left
      ventricle increased significantly with aging and exposure to SHS. Exposure to SHS
      elevated TGFbeta1/p-Smad2/3/CTGF and MMP2/MMP9 protein expression levels (p <
      0.05). No significant differences in FGF-2 and UPA protein expression were noted
      as a result of SHS exposure. However, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 protein
      expression were suppressed by SHS exposure. We also observed increased TGFbeta1/p
      Smad2/3/CTGF (p < 0.01), FGF-2/UPA (p < 0.05) and decreased TIMPs protein
      expression levels. Corresponding MMP2 and MMP9 upregulation occurred with aging
      and exposure to SHS. TGFbeta1/p-Smad2/3/CTGF and FGF-2/UPA protein expression
      from SHS exposure were higher than that from aging. In contrast, MMP2 and MMP9
      were increased in aging rats compared with SHS exposed rats (p < 0.05); however,
      TIMP-1 (p < 0.01), TIMP-2 (p < 0.01) and TIMP-3 (p < 0.05) were decreased. TIMP-4
      protein expression levels were decreased compared with SHS exposed rats (p <
      0.01). CONCLUSIONS: Aging and SHS exposure in rats will produce elevated
      fibrosis. Exposure to SHS will accelerate aging and left ventricular fibrosis.

PMID- 27713610
TI  - Hydrogen Sulfide Modulates the S-Nitrosoproteome and the Mitochondrial Morphology
      in Endothelial Cells.
AB  - BACKGROUND: Hydrogen sulfide (H2S) is one of the endogenous gaseous molecules
      promoting the production of nitric oxide (NO) which has cardioprotective
      functions. However, the role of the H2S-mediated protein S-nitrosoproteome and
      its subsequent physiological response remains unclear. METHODS: Endothelial cells
      EAhy 926 were treated with 50 MUM of H2S for 2 hours. The NO bound S
      nitrosoproteins were purified by a biotin-switch and then digested by trypsin.
      Resulting peptides from control and H2S treatment were separately labeled by
      isobaric tag for relative and absolute quantitation 114/115, quantified by liquid
      chromatography tandem-mass spectrometry and analyzed by ingenuity pathway
      analysis (IPA) software. The microP software was applied to analyze the
      morphological changes of mitochondria. RESULTS: With the treatment of H2S, 416 S
      nitrosylated proteins were identified. IPA analysis showed that these proteins
      were involved in five signaling pathways. The NO-bound cysteine residues and the
      S-nitrosylation levels (115/114) were shown for ten S-nitrosoproteins. Western
      blot further verified the S-nitrosylation of thioredoxin-dependant peroxide
      reductase, cytochrome c oxidase and cytochrome b-c1 complex that are involved in
      the mitochondrial signaling pathway. H2O2-induced mitochondrial swelling can be
      reduced by the pretreatment of H2S. CONCLUSIONS: The H2S-mediated endothelial S
      nitrosoproteome has been confirmed. In the present study, we have proposed the
      cardioprotective role of H2S via maintaining mitochondrial homeostasis.

PMID- 27713611
TI  - Fontan Operation in a Patient with Severe Hypoplastic Right Pulmonary Artery,
      Single Ventricle, and Heterotaxy Syndrome.
AB  - Assessment of the pulmonary circulation status including pressure, resistance,
      size, and absence of anatomical distortion, is crucial to the successful Fontan
      operation. Most patients are found to have acceptable pulmonary arteries after
      previous palliation, although some degree of distortion is not uncommon. However,
      in rare instances, some patients have only one functioning lung with another
      pulmonary artery seriously hypoplastic or atretic. For theses patients,
      completion of a Fontan operation will be challenging. We reported a 17-year-old
      girl with a single ventricle and heterotaxy syndrome and only her left lung
      functioning, who underwent one-lung Fontan operation with a satisfactory result.

PMID- 27713612
TI  - Longitudinal Stent Deformation Caused by Retraction of the Looped Main Branch
      Guidewire.
AB  - A 66-year-old male was treated percutaneously for a bifurcation lesion of the
      left anterior descending coronary artery by provisional stenting using the jailed
      wire technique. After successfully stenting the main branch, retraction of the
      looped main branch guidewire was impossible. After using an intravascular
      ultrasound we discovered the guidewire was entangled with a stent strut.
      Thereafter, the proximal stent elongated after retraction. With the support of an
      over-the-wire microcatheter, we finally pulled out the entrapped guidewire. This
      rare complication should remind physicians that it is important to prevent the
      distal guidewire from being looped while retracting it through a stent,
      regardless of whether it is in the side branch or main vessel. If the guidewire
      becomes entangled with a stent, a microcatheter or low-profile balloon can be
      advanced to rescue it before the stent is damaged. Furthermore, the microcather
      should be maintained after successful retraction of the entangled guidewire to
      facilitate further wiring and subsequent rescue angioplasty as necessary.

PMID- 27713613
TI  - Young Adult Patent Ductus Arteriosus Treated with Endovascular Stent Grafting.
AB  - Endovascular stent-grafting is an alternative treatment for adult patent ductus
      arteriosus (PDA), especially in elderly patients. Regarding young adults,
      endovascular therapy is a reasonable choice if the landing zone is sufficient. In
      this study, we report on a young adult with PDA successfully treated with
      endovascular stent-grafting.

PMID- 27713614
TI  - Using Rivaroxaban as Thrombolytic Treatment for a Patient of Pedal Arch Arterial
      Thrombosis with Suboptimal Result of Endovascular Therapy.
AB  - A 77-year-old male with subacute right foot ischemia was treated with
      endovascular therapy to relieve total thrombosis of the pedal arch extending from
      the dorsalis pedis of the anterior tibial artery into the posterior tibial
      artery, plantar segment. Because the procedure was only partially successful,
      rivaroxaban was used for thrombolytic treatment resulting in improvement of the
      patient's ischemic pain and avoidance of gangrenous progression and surgical
      amputation. This is the first report describing successful recanalization of
      pedal arch arterial thrombosis using rivaroxaban in a patient after suboptimal
      results of endovascular therapy.

PMID- 27713615
TI  - Isolation and characterization of new secondary metabolites from Asphodelus
      microcarpus.
AB  - Phytochemical study of the ethanolic extract of Asphodelus microcarpus Salzm. et
      Viv. (Asphodelaceae) resulted in the isolation of two new compounds, methyl-1,4,5
      trihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracene-2-carboxylate (1), and (1R)
      3,10-dimethoxy-5-methyl-1H-1,4-epoxybenzo[h]isochromene (2) as well as three
      known compounds; 3,4-dihydroxy-methyl benzoate (3), 3,4-dihydroxybenzoic acid
      (4), and 6-methoxychrysophanol (5). Compound 1 showed a potent activity against
      methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus with
      IC50 values of 1.5 and 1.2 ug/mL, respectively. Compound 3 showed antileishmanial
      activity with an IC50 value of 33.2 ug/mL. Compound 2 is the first isochromene
      possessing a highly strained 1,4-epoxy moiety. The structure elucidation of
      isolated metabolites was carried out using spectroscopic data, the absolute
      configuration of 2 based on optical rotation and electronic circular dichroism
      experiments and calculations.

PMID- 27713616
TI  - Cognitive Behavioural Suicide Prevention for Male Prisoners: Case examples.
AB  - Suicide is a serious public health problem but a problem that is preventable.
      This complex and challenging problem is particularly prevalent amongst prisoners;
      associated with a five-fold increase in risk compared to the general community.
      Being in prison can lead people to experience fear, distrust, lack of control,
      isolation, and shame, which is often experienced as overwhelming and intolerable
      with some choosing suicide as a way to escape. Few effective psychological
      interventions exist to prevent suicide although cognitive behaviour therapies
      appear to offer some promise. Offering cognitive behaviour suicide prevention
      (CBSP) therapy to high risk prisoners may help to reduce the likelihood of
      preventable self-inflicted deaths. In this paper we present three cases drawn
      from a randomised controlled trial designed to investigate the feasibility of
      CBSP for male prisoners. Implications of the current findings for future research
      and clinical practice are considered.

PMID- 27713617
TI  - Effects of laser in situ keratomileusis on mental health-related quality of life.
AB  - PURPOSE: The aims of our study were to investigate whether laser in situ
      keratomileusis (LASIK) improves health-related quality of life (HRQoL) and to
      identify factors that affect postoperative HRQoL. MATERIALS AND METHODS: A total
      of 213 Japanese patients who underwent primary LASIK were analyzed in this study.
      The average age of patients was 35.0+/-9.4 years. The subjects were asked to
      answer questions regarding subjective quality of vision, satisfaction, and
      quality of life (using the Japanese version of 36-Item Short Form Health Survey
      Version 2) at three time points: before LASIK, 1 month after LASIK, and 6 months
      after LASIK. Longitudinal changes over 6 months in the outputs of mental
      component summary (MCS) score and the physical component summary (PCS) score from
      the 36-Item Short Form Health Survey Version 2 questionnaire were compared
      between time points using a linear mixed-effects model. Delta MCS and PCS were
      calculated by subtracting the postoperative score (1 month after LASIK) from the
      preoperative score. Preoperative and postoperative factors associated with a
      change in the MCS score or PCS score were evaluated via a linear regression
      model. RESULTS: The preoperative MCS score was 51.0+/-9.4 and increased to 52.0+/
      9.8 and 51.5+/-9.6 at 1 month and 6 months after LASIK, respectively, and the
      trend for the change from baseline in MCS through 6 months was significant
      (P=0.03). PCS score did not change following LASIK. Delta MCS was significantly
      negatively associated with preoperative spherical equivalent, axial length, and
      postoperative quality of vision, after adjusting for potential confounding
      factors. CONCLUSION: Mental HRQoL is not lost with LASIK, and LASIK may improve
      mental HRQoL. Preoperative axial length may predict postoperative mental HRQoL.

PMID- 27713618
TI  - Radiolabeled tirofiban - a potential radiopharmaceutical for detection of deep
      venous thrombosis.
AB  - AIM: The aim of this study was to investigate the possibility of using
      99mtechnetium (99mTc)-labeled tirofiban (a reversible antagonist of glycoprotein
      IIb/IIIa) for detection of deep venous thrombosis (DVT) in rats without causing
      an antiplatelet effect. METHODS: The ability of in vitro tirofiban to inhibit
      adenosine 5'-diphosphate (ADP)-induced platelet aggregation was evaluated using
      optical aggregometer. Binding of 99mTc-tirofiban to platelets was evaluated.
      Serum levels of unlabeled (a validated high performance liquid chromatography
      method) and 99mTc-tirofiban after single intravenous injection were evaluated in
      male Wistar rats with or without induced DVT (femoral vein ligation model), and
      the rats were also subjected to whole body scintigraphy. RESULTS: Tirofiban in
      vitro inhibits ADP-induced aggregation of human platelets in a dose- and
      concentration-dependent manner (10 nM to 2 MUM), but only if it is added before
      ADP and not after ADP. 99mTc labeling did not affect the ability of tirofiban to
      bind to either human or rat platelets, nor did it affect tirofiban
      pharmacokinetics in intact rats or in animals with induced DVT. When 99mTc
      tirofiban was injected to rats after induction of DVT, at a molar dose lower than
      the one showing only a weak antiaggregatory effect in vitro, whole body
      scintigraphy indicated localization of 99mTc-tirofiban around the place of the
      induced DVT. CONCLUSION: 99mTc labeling of tirofiban does not affect its ability
      to bind to glycoprotein IIb/IIIa or its in vivo pharmacokinetics in rats, either
      intact or with DVT. A low, nonantiaggregatory dose of 99mTc-tirofiban may be used
      to visualize DVT at an early stage.

PMID- 27713619
TI  - Spotlight on sirukumab for the treatment of rheumatoid arthritis: the evidence to
      date.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease primarily
      affecting synovial joints and is characterized by persistent high-grade systemic
      inflammation. Proinflammatory cytokines, particularly interleukin-6 (IL-6), are
      of crucial importance in the pathogenesis of the disease, driving both joint
      inflammation and extra-articular comorbidities. Tocilizumab, a humanized IL-6
      receptor-inhibiting monoclonal antibody, has been the first, and, to date, the
      only, IL-6 inhibitor approved for the treatment of RA. Many studies have
      demonstrated the potency and effectiveness of tocilizumab in controlling disease
      activity and radiological progression of RA. These successful results have
      encouraged the development of novel IL-6 inhibitors, among which a promising
      agent is sirukumab (SRK), a human anti-IL-6 monoclonal antibody currently under
      evaluation in Phase II/III studies in patients with RA, systemic lupus
      erythematosus, giant-cell arteritis, and major depressive disorder. The evidence
      to date indicates SRK as an effective and well-tolerated new therapeutic tool for
      patients with active RA, with some preliminary data suggesting a specific
      beneficial impact on relevant systemic complications associated with the disease,
      such as depression and cardiovascular disease. Conversely, although
      pathophysiological considerations make plausible the hypothesis that IL-6
      blockade with SRK may also be beneficial in the treatment of many diseases other
      than RA (either autoimmune or not), available clinical data in patients with
      systemic lupus erythematosus do not seem to support this view, also giving rise
      to potentially relevant concerns about drug safety. If large Phase III clinical
      trials currently in progress in patients with RA confirm the efficacy and
      tolerability of SRK, then in the long term, this drug could, in the near future,
      occupy a place in the treatment of the disease, potentially also opening the
      doors to a more extended use of SRK in a wide range of disorders in which IL-6
      plays a key pathogenic role.

PMID- 27713620
TI  - Evaluation of effects of various drugs on platelet functions using phorbol 12
      myristate 13-acetate-induced megakaryocytic human erythroid leukemia cells.
AB  - BACKGROUND: The hyperfunction and activation of platelets have been strongly
      implicated in the development and recurrence of arterial occlusive disease, and
      various antiplatelet drugs are used to treat and prevent such diseases. New
      antiplatelet drugs and many other drugs have been developed, but some drugs may
      have adverse effects on platelet functions. OBJECTIVE: The aim of this study was
      to establish an evaluation method for evaluating the effect and adverse effect of
      various drugs on platelet functions. MATERIALS AND METHODS: Human erythroid
      leukemia (HEL) cells were used after megakaryocytic differentiation with phorbol
      12-myristate 13-acetate as an alternative to platelets. Drugs were evaluated by
      changes in intracellular Ca2+ concentration ([Ca2+]i) mobilization in Fura2
      loaded phorbol 12-myristate 13-acetate-induced HEL cells. Aspirin and cilostazol
      were selected as antiplatelet drugs and ibuprofen and sodium valproate as other
      drugs. RESULTS: There was a positive correlation between [Ca2+]i and platelet
      aggregation induced by thrombin. Aspirin (5.6-560 uM) and cilostazol (5-10 uM)
      significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration
      dependent manner. On the other hand, ibuprofen (8-200 uM) and sodium valproate
      (50-1,000 ug/mL) also significantly inhibited thrombin-induced increases in
      [Ca2+]i in a concentration-dependent manner. Furthermore, the interaction effects
      of the simultaneous combined use of aspirin and ibuprofen or sodium valproate
      were evaluated. When the inhibitory effect of aspirin was higher than that of
      ibuprofen, the effect of aspirin was reduced, whereas when the inhibitory effect
      of aspirin was lower than that of ibuprofen, the effect of ibuprofen was reduced.
      The combination of aspirin and sodium valproate synergistically inhibited
      thrombin-induced [Ca2+]i. CONCLUSION: It is possible to induce HEL cells to
      differentiate into megakaryocytes, which are a useful model for the study of
      platelet functions, and the quantification of the inhibition of thrombin-induced
      increases in [Ca2+]i is applicable to the evaluation of the effects of various
      drugs on platelets.

PMID- 27713621
TI  - "My patients are better than yours": optimistic bias about patients' medication
      adherence by European health care professionals.
AB  - OBJECTIVES: The objectives of this study were to determine the perceptions of
      European physicians, nurses, and pharmacists about the extent of nonadherence by
      patients in their country relative to their perception of nonadherence by their
      own patients, and to investigate the occurrence of optimistic bias about
      medication adherence. The study explored a key cognitive bias for prevalence and
      likelihood estimates in the context of health care professionals' beliefs about
      patients' use of medicines. METHODS: A cross-sectional online survey of 3,196
      physicians (855), nurses (1,294), and pharmacists (1,047) in ten European
      countries (Austria, Belgium, England, France, Germany, Hungary, the Netherlands,
      Poland, Portugal, and Switzerland) was used. RESULTS: Participants differed in
      their perceptions of the prevalence of medication adherence initiation,
      implementation, and persistence present in their own patients with a chronic
      illness in comparison to patients with a chronic illness in general. Health care
      professionals demonstrated optimistic bias for initiation and persistence with
      medicine taking, perceiving their own patients to be more likely to initiate and
      persist with treatment than other patients, but reported significantly lower
      prevalence of medication adherence levels for their own patients than for
      patients in general. This finding is discussed in terms of motivational and
      cognitive factors that may foster optimistic bias by health care professionals
      about their patients, including heightened knowledge of, and positive beliefs
      about, their own professional competence and service delivery relative to care
      and treatment provided elsewhere. CONCLUSION: Health care professionals in Europe
      demonstrated significant differences in their perceptions of medication adherence
      prevalence by their own patients in comparison to patients in general. Some
      evidence of optimistic bias by health care professionals about their patients'
      behavior is observed. Further social cognitive theory-based research of health
      care professional beliefs about medication adherence is warranted to enable
      theory-based practitioner-focused interventions to be tested and implemented.

PMID- 27713622
TI  - Patient preferences for treatment of multiple sclerosis with disease-modifying
      therapies: a discrete choice experiment.
AB  - OBJECTIVES: To assess disease-modifying therapy (DMT) preferences in a population
      of patients with multiple sclerosis (MS) and to estimate the association between
      sociodemographic and clinical factors and these preferences. METHODS: Preferences
      for DMTs attributes were measured using a discrete choice experiment. Analysis of
      preferences was assessed using mixed-logit hierarchical Bayes regression. A
      multilinear regression was used to evaluate the association between the
      preferences for each attribute and patients' demographic and clinical
      characteristics. A Student's t-test or Welch's t-test was used for subgroup
      comparisons. RESULTS: A total of 125 patients were included in the final analysis
      (62.9% female, mean age 44.5 years, 71.5% with relapsing-remitting MS diagnosis).
      The most important factor for patients was the possibility of suffering from the
      side effects of the treatment (relative importance [RI] =50%), followed by a
      delay in disease progression (RI =19.4%), and route and frequency of
      administration (RI =14.3%). According to maximum acceptable risk, patients were
      willing to accept an increase of 3.8% in severity of side effects, for a delay of
      1 year in disease progression. Treatment duration was the most prevalent factor
      affecting preferences, followed by the age of patients, type of MS, level of
      education, and the type of current treatment. Patients treated orally were
      significantly more concerned about the route and frequency of administration
      (P=0.026) than patients on injectable therapy. Naive patients stated
      significantly less importance to prevention of relapses (P=0.021) and
      deterioration of the capacity for performing usual daily life activities
      (P=0.015). Finally, patients with >5 years since diagnosis were significantly
      less concerned about preventing disease progression (P=0.021), and more concerned
      about treatment side effects (P=0.052) than compared with patients with <5 years
      of MS history. CONCLUSION: The most important attribute for MS patients was side
      effects of DMTs, followed by delay in disability progression. Experience with
      DMTs and time since MS diagnosis changed patients' preferences. These results
      give information to adjust new DMT treatment in order to satisfy patients'
      preferences and therefore, improve adherence to treatment.

PMID- 27713623
TI  - Patterns of scheduled follow-up appointments following hospitalization for heart
      failure: insights from an urban medical center in the United States.
AB  - OBJECTIVES: Although postdischarge outpatient follow-up appointments after a
      hospitalization for heart failure represent a potentially effective strategy to
      prevent heart failure readmissions, patterns of scheduled follow-up appointments
      upon discharge are poorly described. We aimed to characterize real-world patterns
      of scheduled follow-up appointments among adult patients with heart failure upon
      hospital discharge. PATIENTS AND METHODS: This was a retrospective cohort study
      performed at a large urban academic center in the United States among adults
      hospitalized with a principal diagnosis of congestive heart failure between
      January 1, 2013, and December 31, 2014. Patient demographics, administrative
      data, clinical parameters, echocardiographic indices, and scheduled postdischarge
      outpatient follow-up appointments were collected. RESULTS: Of the 796 patients
      hospitalized for heart failure, just over half of the cohort had a scheduled
      follow-up appointment upon discharge. Follow-up appointments were less likely
      among patients who were white and had heart failure with preserved ejection
      fraction and more likely among patients with Medicaid and chronic obstructive
      pulmonary disease. In an adjusted multivariable regression model, age >=65 years
      was inversely associated with a scheduled follow-up appointment upon hospital
      discharge, despite higher rates of several cardiovascular and noncardiovascular
      comorbidities. CONCLUSION: Just half of the patients discharged home following a
      hospitalization for heart failure had a follow-up appointment scheduled,
      representing a missed opportunity to provide a recommended care transition
      intervention. Despite a greater burden of both cardiovascular and
      noncardiovascular comorbidities, older adults (age >=65 years) were less likely
      to have a follow-up appointment scheduled upon discharge compared with younger
      adults, revealing a disparity that warrants further investigation.

PMID- 27713624
TI  - Evaluation of the Master's curriculum for elderly nursing: a qualitative study.
AB  - BACKGROUND: Improving the quality of health care and rehabilitation for the
      elderly is one of the most important priorities of the health care system. Given
      the importance of evaluating the strengths and weaknesses of any program after
      its implementation, this study was conducted to identify the advantages and
      weaknesses of a geriatric nursing program at Tehran University of Medical
      Sciences. METHODS: This was a qualitative study, and the study population
      comprised students, graduates, and professors of geriatric nursing at the Master
      of Science level. Data were collected through face-to-face interviews and focus
      groups. Sixteen interviews were conducted. The interview guide was used as a
      research tool. Interviews continued until data saturation was reached.
      Conventional content analysis was used to analyze the data. RESULTS: Three main
      themes including "motivation to enter geriatric nursing", "lack of employment
      groundwork", and "lack of practical implementation of the curriculum" were the
      main findings of the study. CONCLUSION: Efforts to restructure the administrative
      system and employment can deter geriatric nursing students from simply earning a
      degree and actually encourage them to learn the required content. Appraisal and
      improvement of education facilities for student recruitment can guarantee the
      practical implementation of the curriculum. Drafting policies to attract
      graduates in clinical environments, opening up employment opportunities,
      providing organizational positions for the recruitment of this group, as well as
      dedicating some wards for elderly special care and providing nursing care to
      elderly people only can increase students' motivation to learn and their hopes of
      good job prospects.

PMID- 27713625
TI  - Impact of pharmacist interventions in older patients: a prospective study in a
      tertiary hospital in Germany.
AB  - BACKGROUND: Inappropriate pharmacotherapy among older adults remains a critical
      issue in our health care systems. Besides polypharmacy and multiple
      comorbidities, the age-related pharmacokinetic and pharmacodynamic changes may
      increase the risk of adverse drug reactions and medication errors. OBJECTIVE: The
      main target of this study was to describe the characteristics of pharmaceutical
      interventions in two geriatric wards (orthogeriatric ward and geriatric day unit)
      of a general teaching hospital and to evaluate the clinical significance of the
      detected medication errors. MATERIALS AND METHODS: The study was conducted
      between August 2014 and October 2015 and was based on a triple approach that
      included validation of medical orders, medication reconciliation at patients'
      admission, and a predischarge planning appointment with the patient. The
      validation of medical orders was based on analyzing the suitability of the drugs
      prescribed, the drug dose depending on the patient's characteristics, the
      presence of contraindications and interactions between drugs, and the proposal of
      alternative drugs included in the hospital formulary. RESULTS: A total of 2,307
      interventions associated to a medication error in 15,282 medical orders for 1,859
      older patients were recorded. The greater part of the interventions carried out
      on the orthogeriatric ward at admission and at discharge were due to omission of
      a drug in the medical order (20.0%) and clinically significant interactions
      requiring monitoring (30.4%), respectively. The main factor triggering
      pharmacist's recommendations on the geriatric day unit was clinically significant
      interactions (21.1%). With regard to the clinical severity of the detected
      errors, 68.1% were considered significant, 24.8% were of minor significance, and
      7.2% were clinically serious. CONCLUSION: Our findings show the importance of
      clinical pharmacist involvement in the optimization of pharmacotherapy in older
      adults, ensuring that they receive effective, safe, and efficient drug therapy.

PMID- 27713626
TI  - Increased mortality in patients with severe COPD associated with high-intensity
      exercise: a preliminary cohort study.
AB  - INTRODUCTION: Intensity of exercise is believed to be a key determinant of
      response to chronic obstructive pulmonary disease (COPD) rehabilitation. We
      hypothesized that a higher intensity of exercise, in combination with
      physiotherapist-led instructions and education in management of breathlessness,
      would lead to better self-management, possibly delaying calls to the emergency
      service and preventing hospitalization. OBJECTIVE: We aimed to test this
      hypothesis in a subsequent randomized trial, and in order to test study processes
      and estimate hospitalization rates, we did a small preliminary prospective cohort
      study on severe COPD patients referred to outpatient rehabilitation. METHODS: In
      2013, four rehabilitation courses were scheduled (spring, summer, autumn, and
      winter) each lasting 8 weeks and including eight to ten patients. This
      preliminary study was designed as a controlled cohort study. The bi-weekly
      exercise sessions in the spring and autumn courses included a high-intensity
      walking exercise at 95% of estimated VO2 max for as long as possible. The other
      two rehabilitation courses included the usual walking exercise intensity (85% of
      estimated VO2 max). Hospitalization rates were assessed from the participants'
      medical records in an 18-month period. RESULTS: We were able to enroll 31
      patients in total (15 in the high-intensity exercise group and 16 in regular
      intensity). There were no group differences in the hospitalization rates.
      However, during review of the medical records, we observed a striking mortality
      rate among participants who had attended the high-intensity rehabilitation
      courses (five deaths) compared to the standard rehabilitation (zero deaths). Four
      of the five deaths were COPD exacerbations. Fisher's exact test was statistically
      significant (P=0.046), as was a log-rank test (P=0.019) of the Kaplan-Meier
      estimated survival rates. CONCLUSION: These results from this small preliminary
      cohort study are alarming and raise concerns about the possible serious risks
      associated with high-intensity exercise rehabilitation of severe COPD patients.

PMID- 27713628
TI  - Can resistive breathing injure the lung? Implications for COPD exacerbations.
AB  - In obstructive lung diseases, airway inflammation leads to bronchospasm and thus
      resistive breathing, especially during exacerbations. This commentary discusses
      experimental evidence that resistive breathing per se (the mechanical stimulus)
      in the absence of underlying airway inflammation leads to lung injury and
      inflammation (mechanotransduction). The potential implications of resistive
      breathing-induced mechanotrasduction in COPD exacerbations are presented along
      with the available clinical evidence.

PMID- 27713627
TI  - Elevated circulating PAI-1 levels are related to lung function decline, systemic
      inflammation, and small airway obstruction in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type
      plasminogen activator receptor (suPAR) participate in inflammation and tissue
      remolding in various diseases, but their roles in chronic obstructive pulmonary
      disease (COPD) are not yet clear. This study aimed to investigate if PAI-1 and
      suPAR were involved in systemic inflammation and small airway obstruction (SAO)
      in COPD. METHODS: Demographic and clinical characteristics, spirometry
      examination, and blood samples were obtained from 84 COPD patients and 51 healthy
      volunteers. Serum concentrations of PAI-1, suPAR, tissue inhibitor of
      metalloproteinase-1 (TIMP-1), Matrix metalloproteinase-9 (MMP-9), and C-reactive
      protein (CRP) were detected with Magnetic Luminex Screening Assay. Differences
      between groups were statistically analyzed using one-way analysis of variance or
      chi-square test. Pearson's partial correlation test (adjusted for age, sex, body
      mass index, cigarette status, and passive smoke exposure) and multivariable
      linear analysis were used to explore the relationships between circulating PAI-1
      and indicators of COPD. RESULTS: First, we found that serum PAI-1 levels but not
      suPAR levels were significantly increased in COPD patients compared with healthy
      volunteers (125.56+/-51.74 ng/mL versus 102.98+/-36.62 ng/mL, P=0.007). Then, the
      correlation analysis showed that circulating PAI-1 was inversely correlated with
      pulmonary function parameters including the ratio of forced expiratory volume in
      1 second to forced vital capacity (FEV1/FVC), FEV1/Pre (justified r=-0.308,
      P<0.001; justified r=-0.295, P=0.001, respectively) and SAO indicators such as
      FEV3/FVC, MMEF25-75/Pre (justified r=-0.289, P=0.001; justified r=-0.273,
      P=0.002, respectively), but positively related to the inflammatory marker CRP
      (justified r=0.351, P<0.001), the small airway remolding biomarker TIMP-1, and
      MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively).
      Besides, multivariable linear analysis showed that FEV1/FVC, CRP, and TIMP-1 were
      independent parameters associated with PAI-1. CONCLUSION: Our findings first
      illustrate that elevated serum PAI-1 levels are related to the lung function
      decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play
      critical roles in the pathogenesis of COPD.

PMID- 27713629
TI  - Importance of fractional exhaled nitric oxide in the differentiation of asthma
      COPD overlap syndrome, asthma, and COPD.
AB  - BACKGROUND: Fractional exhaled nitric oxide (FeNO) is an easy, sensitive,
      reproducible, and noninvasive marker of eosinophilic airway inflammation.
      Accordingly, FeNO is extensively used to diagnose and manage asthma. Patients
      with COPD who share some of the features of asthma have a condition called asthma
      COPD overlap syndrome (ACOS). The feasibility of using FeNO to differentiate ACOS
      patients from asthma and COPD patients remains unclear. METHODS: From February
      2013 to May 2016, patients suspected with asthma and COPD through physician's
      opinion were subjected to FeNO measurement, pulmonary function test (PFT), and
      bronchial hyperresponsiveness or bronchodilator test. Patients were divided into
      asthma alone group, COPD alone group, and ACOS group according to a clinical
      history, PFT values, and bronchial hyperresponsiveness or bronchodilator test.
      Receiver operating characteristic (ROC) curves were obtained to elucidate the
      clinical functions of FeNO in diagnosing ACOS. The optimal operating point was
      also determined. RESULTS: A total of 689 patients were enrolled in this study:
      500 had asthma, 132 had COPD, and 57 had ACOS. The FeNO value in patients with
      ACOS was 27 (21.5) parts per billion (ppb; median [interquartile range]), which
      was significantly higher than that in the COPD group (18 [11] ppb). The area
      under the ROC curve was estimated to be 0.783 for FeNO. Results also revealed an
      optimal cutoff value of >22.5 ppb FeNO for differentiating ACOS from COPD
      patients (sensitivity 70%, specificity 75%). CONCLUSION: FeNO measurement is an
      easy, noninvasive, and sensitive method for differentiating ACOS from COPD. This
      technique is a new perspective for the management of COPD patients.

PMID- 27713630
TI  - Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded
      with Akebia saponin D-phospholipid complex.
AB  - BACKGROUND: Akebia saponin D (ASD) exerts various pharmacological activities but
      with poor oral bioavailability. In this study, a self-nanoemulsifying drug
      delivery system (SNEDDS) based on the drug-phospholipid complex technique was
      developed to improve the oral absorption of ASD. METHODS: ASD-phospholipid
      complex (APC) was prepared using a solvent-evaporation method and characterized
      by infrared spectroscopy, differential scanning calorimetry, morphology
      observation, and solubility test. Oil and cosurfactant were selected according to
      their ability to dissolve APC, while surfactant was chosen based on its
      emulsification efficiency in SNEDDS. Pseudoternary phase diagrams were
      constructed to determine the optimized APC-SNEDDS formulation, which was
      characterized by droplet size determination, zeta potential determination, and
      morphology observation. Robustness to dilution and thermodynamic stability of
      optimized formulation were also evaluated. Subsequently, pharmacokinetic
      parameters and oral bioavailability of ASD, APC, and APC-SNEDDS were investigated
      in rats. RESULTS: The liposolubility significantly increased 11.4-fold after
      formation of APC, which was verified by the solubility test in n-octanol. Peceol
      (Glyceryl monooleate [type 40]), Cremophor(r) EL (Polyoxyl 35 castor oil), and
      Transcutol HP (Diethylene glycol monoethyl ether) were selected as oil,
      surfactant, and cosurfactant, respectively. The optimal formulation was composed
      of Glyceryl monooleate (type 40), Polyoxyl 35 castor oil, Diethylene glycol
      monoethyl ether, and APC (1:4.5:4.5:1.74, w/w/w/w), which showed a particle size
      of 148.0+/-2.7 nm and a zeta potential of -13.7+/-0.92 mV after dilution with
      distilled water at a ratio of 1:100 (w/w) and good colloidal stability.
      Pharmacokinetic studies showed that APC-SNEDDS exhibited a significantly greater
      Cmax1 (733.4+/-203.8 ng/mL) than ASD (437.2+/-174.2 ng/mL), and a greater Cmax2
      (985.8+/-366.6 ng/mL) than ASD (180.5+/-75.1 ng/mL) and APC (549.7+/-113.5
      ng/mL). Compared with ASD, Tmax1 and Tmax2 were both remarkably shortened by APC
      SNEDDS. The oral bioavailability in rats was enhanced significantly to 183.8% and
      431.8% by APC and APC-SNEDDS, respectively. CONCLUSION: These results indicated
      that APC-SNEDDS was a promising drug delivery system to enhance the oral
      bioavailability of ASD.

PMID- 27713632
TI  - Is there any superiority among diagnostic methods in organizing pneumonia in
      terms of clinical features of the patients?
AB  - BACKGROUND: Organizing pneumonia (OP) can be idiopathic or secondary to some
      clinical situations. If an etiological cause is not present, this phenomenon is
      called cryptogenic OP. Secondary OP is associated with various diseases that are
      known to induce the OP. OBJECTIVES: The aim of this study was to evaluate the
      clinical features of the cases with OP and compare the patients diagnosed by
      bronchoscopic transbronchial biopsy with patients diagnosed by surgical lung
      biopsy. PATIENTS AND METHODS: Medical records of 41 patients diagnosed with OP
      between 2004 and 2014 were reviewed retrospectively. RESULTS: Totally, 41
      patients with OP were identified. In all, 39.02% of the cases were diagnosed by
      bronchoscopic methods, and 60.97% of the cases were diagnosed by surgical
      procedures. Although the frequency of ground glass opacities, consolidations, and
      micronodules was higher in the group diagnosed by bronchoscopy, mass-like lesions
      were more common in the cases diagnosed by surgery. Bronchoscopy, performed in 30
      patients totally, had a diagnostic efficacy of 53.33%. Diagnostic value of
      bronchoscopy was significantly higher in cryptogenic OPs. Although diffuse
      radiological pattern was more common in "successful bronchoscopy" group,
      frequency of focal pattern was higher in "failed bronchoscopy" group. Ground
      glass opacity in successful bronchoscopy group and mass-like lesions in failed
      bronchoscopy group reached significant differences. CONCLUSION: There were
      significant differences between the diagnostic procedures in terms of
      radiological patterns. This is the first study about the relationship between the
      diagnostic methods and the characteristics of OP.

PMID- 27713631
TI  - A longitudinal, event-related potential pilot study of adult obsessive-compulsive
      disorder with 1-year follow-up.
AB  - AIM: Earlier brain imaging research studies have suggested that brain
      abnormalities in obsessive-compulsive disorder (OCD) normalize as clinical
      symptoms improve. However, although many studies have investigated event-related
      potentials (ERPs) in patients with OCD compared with healthy control subjects, it
      is currently unknown whether ERP changes reflect pharmacological and
      psychotherapeutic effects. As such, the current study examined the neurocognitive
      components of OCD to elucidate the pathophysiological abnormalities involved in
      the disorder, including the frontal-subcortical circuits. METHODS: The Yale-Brown
      Obsessive-Compulsive Scale was used to evaluate 14 adult patients with OCD. The
      present study also included ten age-, sex-, and IQ-matched controls. The P300 and
      mismatch negativity (MMN) components during an auditory oddball task at baseline
      for both groups and after 1 year of treatment for patients with OCD were
      measured. RESULTS: Compared with controls, P300 amplitude was attenuated in the
      OCD group at Cz and C4 at baseline. Pharmacotherapy and psychotherapy treatment
      for 1 year reduced OCD symptomology. P300 amplitude after 1 year of treatment was
      significantly increased, indicating normalization compared with baseline at Fz,
      Cz, C3, and C4. We found no differences in P300 latency, MMN amplitude, or MMN
      latency between baseline and after one year of treatment. CONCLUSION: ERPs may be
      a useful tool for evaluating pharmacological and cognitive behavioral therapy in
      adult patients with OCD.

PMID- 27713634
TI  - Risk factors for nosocomial nontraumatic coma: sepsis and respiratory failure.
AB  - BACKGROUND: Coma's are a major cause of clinical deterioration or death.
      Identification of risks that predispose to coma are important in managing
      patients; however, the risk factors for nosocomial nontraumatic coma (NNC) are
      not well known. Our aim was to investigate the risk factors in patients with NNC.
      METHODS: A retrospective case-control design was used to compare patients with
      NNC and a control group of patients without coma in a population-based cohort of
      263 participants from the neurological intensive care unit in Shuyang County
      People's Hospital of Northern China. Coma was diagnosed by a Glasgow Coma Scale
      score <=8. Adjusted odds ratios for patients with NNC were derived from
      multivariate logistic regression analyses. RESULTS: A total of 96 subjects had
      NNC. The prevalence of NNC was 36.5% among the subjects. Among these, 82% had
      acute cerebrovascular etiology. Most of the NNC usually occurred at day 3 after
      admission to the neurological intensive care unit. Patients with NNC had higher
      hospital mortality rates (67.7% vs 3%, P<0.0001) and were more likely to have a
      central herniation (47.9% vs 0%, P<0.001) or uncal herniation (11.5% vs 0%,
      P<0.001) than those without NNC. Multiple logistic regression showed that
      systemic inflammatory response syndrome-positive sepsis (odds ratio =4, 95%
      confidence interval =1.875-8.567, P<0.001) and acute respiratory failure (odds
      ratio =3.275, 95% confidence interval =1.014-10.573, P<0.05) were the factors
      independently associated with a higher risk of NNC. CONCLUSION: Systemic
      inflammatory response syndrome-positive sepsis and acute respiratory failure are
      independently associated with an increased risk of NNC. This information may be
      important for patients with NNC.

PMID- 27713633
TI  - Comparison of the acute-phase response after laparoscopic versus open
      aortobifemoral bypass surgery: a substudy of a randomized controlled trial.
AB  - PURPOSE: Minimally invasive surgical techniques have been shown to reduce the
      inflammatory response related to a surgical procedure. The main objective of our
      study was to measure the inflammatory response in patients undergoing a totally
      laparoscopic versus open aortobifemoral bypass surgery. This is the first
      randomized trial on subjects in this population. PATIENTS AND METHODS: This is a
      substudy of a larger randomized controlled multicenter trial (Norwegian
      Laparoscopic Aortic Surgery Trial). Thirty consecutive patients with severe
      aortoiliac occlusive disease eligible for aortobifemoral bypass surgery were
      randomized to either a totally laparoscopic (n=14) or an open surgical procedure
      (n=16). The inflammatory response was measured by perioperative monitoring of
      serum interleukin-6 (IL-6), IL-8, and C-reactive protein (CRP) at six different
      time points. RESULTS: The inflammatory reaction caused by the laparoscopic
      procedure was reduced compared with open surgery. IL-6 was significantly lower
      after the laparoscopic procedure, measured by comparing area under the curve
      (AUC), and after adjusting for the confounding effect of coronary heart disease
      (P=0.010). The differences in serum levels of IL-8 and CRP did not reach
      statistical significance. CONCLUSION: In this substudy of a randomized controlled
      trial comparing laparoscopic and open aortobifemoral bypass surgeries, we found a
      decreased perioperative inflammatory response after the laparoscopic procedure
      measured by comparing AUC for serum IL-6.

PMID- 27713635
TI  - Weekly nanoparticle albumin-bound paclitaxel in combination with cisplatin versus
      weekly solvent-based paclitaxel plus cisplatin as first-line therapy in Chinese
      patients with advanced esophageal squamous cell carcinoma.
AB  - OBJECTIVE: More effective regimens for advanced esophageal squamous cell
      carcinoma (ESCC) are urgently needed. Therefore, a retrospective study concerning
      the efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin
      (nab-TP) versus solvent-based paclitaxel plus cisplatin (sb-TP) as a first-line
      therapy was conducted in Chinese patients with advanced ESCC. METHODS: From June
      2009 to June 2015, 32 patients were treated with nab-paclitaxel (125 mg/m2) on
      the first and eighth days (30 minutes infusion) and cisplatin (75 mg/m2) on the
      second day every 21 days (nab-TP arm). Also, 43 patients were treated with
      solvent-based paclitaxel (80 mg/m2) intravenously on the first and eighth days
      and the same dose of cisplatin (sb-TP arm). The two groups were compared in terms
      of objective response rate (ORR), disease control rate, progression-free survival
      (PFS), overall survival (OS), and safety profile. OS and PFS were estimated using
      Kaplan-Meier methods to determine associations between chemotherapy regimens and
      survival outcomes. RESULTS: Nab-TP demonstrated a higher ORR (50% vs 30%;
      P=0.082) and disease control rate (81% vs 65%; P=0.124) than sb-TP. Median OS was
      similar for nab-TP and sb-TP (12.5 vs 10.7 months; P=0.269). However, nab-TP
      resulted in a longer median PFS (6.1 months [95% confidence interval: 5.3-6.9])
      than sb-TP (5.0 months [95% confidence interval: 4.4-5.6]) (P=0.029). The most
      common adverse events included anemia, leukopenia, neutropenia, febrile
      neutropenia, and thrombocytopenia in both the groups and no statistically
      significant differences were observed between the groups. With statistically
      significant differences, significantly less grade >=3 peripheral neuropathy,
      arthralgia, and myalgia occurred in the nab-TP arm (all P<0.05). Dose reduction,
      treatment delays, and second-line therapy were similar between the two regimens.
      There were no treatment-related deaths in either group. CONCLUSION: Nab
      paclitaxel plus cisplatin is found to be an effective and tolerable option for
      advanced ESCC in the People's Republic of China.

PMID- 27713636
TI  - Clinical use of cabozantinib in the treatment of advanced kidney cancer:
      efficacy, safety, and patient selection.
AB  - Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer
      found in the kidney accounting for ~90% of all kidney cancers. In 2012, there
      were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000
      deaths, with the highest incidence and mortality in Western countries. Despite
      improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for
      RCC, progression remains virtually universal and additional therapies are needed.
      The pivotal results of the METEOR trial led to cabozantinib's designation as a
      breakthrough drug by the US Food and Drug Administration and its approval for
      treatment of advanced RCC in 2016. Subsequent data from the CABOSUN trial, where
      caboxantinib is compared with sunitinib, will provide information on the relative
      activity of cabozantinib as first-line therapy for ccRCC. We review the
      development of cabozantinib in advanced RCC and its role in the treatment
      landscape for advanced RCC.

PMID- 27713637
TI  - Safety and efficacy of sunitinib in patients from Latin America: subanalysis of
      an expanded access trial in metastatic renal cell carcinoma.
AB  - BACKGROUND: Sunitinib is an approved treatment for metastatic renal cell
      carcinoma (mRCC). The safety profile and efficacy of sunitinib were confirmed in
      a global expanded access trial (ClinicalTrials.gov identifier: NCT00130897). This
      report presents a subanalysis of the final trial data from patients in Latin
      America. METHODS: Treatment-naive or previously treated mRCC patients aged >=18
      years received oral sunitinib at a starting dose of 50 mg/day on a 4-weeks-on/2
      weeks-off schedule. Treatment continued until disease progression, unacceptable
      toxicity, or withdrawal of consent. Safety was assessed regularly, and tumor
      measurements were scheduled per local practice (using Response Evaluation
      Criteria in Solid Tumors). RESULTS: In total, 348 patients from Latin America
      received sunitinib. Overall, 75% of patients had two or more sites of metastatic
      disease, 28% were aged >=65 years, 14% had an Eastern Cooperative Oncology Group
      performance status >=2, 9% had brain metastases, 9% had no prior nephrectomy, and
      5% had non-clear cell RCC. Median treatment duration was 8 months, and median
      follow-up was 15.1 months. In total, 326 patients (94%) discontinued treatment,
      primarily due to death (41%) or lack of efficacy (22%). Most treatment-related
      adverse events were of mild to moderate severity (grade 1/2). Mucosal
      inflammation (reported in 54% of patients), diarrhea (53%), and asthenia (41%)
      were the most common any-grade treatment-related adverse events. Asthenia (12%),
      neutropenia (10%), and fatigue and thrombocytopenia (both 9%) were the most
      common grade 3/4 treatment-related adverse events. In total, 311 patients were
      included for tumor response, of whom eight (3%) had a complete response and 46
      (15%) a partial response, yielding an objective response rate of 17%. Median
      duration of response, progression-free survival, and overall survival were 26.7,
      12.1, and 16.9 months, respectively. CONCLUSION: The efficacy and safety profile
      of sunitinib in patients with mRCC from Latin America was comparable to that in
      the entire cohort of the global expanded access trial.

PMID- 27713638
TI  - Nanoradiopharmaceuticals for breast cancer imaging: development,
      characterization, and imaging in inducted animals.
AB  - Monoclonal antibodies as polymeric nanoparticles are quite interesting and endow
      this new drug category with many advantages, especially by reducing the number of
      adverse reactions and, in the case of radiopharmaceuticals, also reducing the
      amount of radiation (dose) administered to the patient. In this study, a
      nanoradiopharmaceutical was developed using polylactic acid (PLA)/polyvinyl
      alcohol (PVA)/montmorillonite (MMT)/trastuzumab nanoparticles labeled with
      technetium-99m (99mTc) for breast cancer imaging. In order to confirm the
      nanoparticle formation, atomic force microscopy and dynamic light scattering were
      performed. Cytotoxicity of the nanoparticle and biodistribution with 99mTc in
      healthy and inducted animals were also measured. The results from atomic force
      microscopy showed that the nanoparticles were spherical, with a size range of
      ~200-500 nm. The dynamic light scattering analysis demonstrated that over 90% of
      the nanoparticles produced had a size of 287 nm with a zeta potential of -14,6
      mV. The cytotoxicity results demonstrated that the nanoparticles were capable of
      reaching breast cancer cells. The biodistribution data demonstrated that the
      PLA/PVA/MMT/trastuzumab nanoparticles labeled with 99mTc have great renal
      clearance and also a high uptake by the lesion, as ~45% of the
      PLA/PVA/MMT/trastuzumab nanoparticles injected were taken up by the lesion. The
      data support PLA/PVA/MMT/trastuzumab labeled with 99mTc nanoparticles as
      nanoradiopharmaceuticals for breast cancer imaging.

PMID- 27713639
TI  - Spotlight on pembrolizumab in non-small cell lung cancer: the evidence to date.
AB  - Immunotherapy with immune checkpoint inhibitors has opened a new arena in cancer
      therapeutics. Pembrolizumab is a highly selective anti-programmed cell death
      protein 1 (PD-1) antibody that has shown efficacy, leading to survival benefit
      and durable responses, in some patients with non-small cell lung cancer (NSCLC).
      It has been approved by the US Food and Drug Administration for the treatment of
      patients with metastatic NSCLC, whose tumors express PD-1 ligand 1 (PD-L1), with
      disease progression on or after platinum-containing chemotherapy. Here, we
      briefly discuss the PD-1/PD-L1 pathway and pembrolizumab before delving into the
      clinical trials that have led to its just-mentioned approval in NSCLC and ongoing
      clinical trials. Finally, we discuss the use of biomarkers, primarily PD-L1, in
      the context of pembrolizumab and NSCLC.

PMID- 27713640
TI  - The efficacy and safety of nivolumab in previously treated advanced non-small
      cell lung cancer: a meta-analysis of prospective clinical trials.
AB  - BACKGROUND: Nivolumab (BMS-936558/ONO-4538) was the first monoclonal antibody
      targeting programmed death (PD)-1. So far, a number of clinical trials on
      nivolumab have showed satisfactory efficacy in treating non-small-cell lung
      cancer (NSCLC). Herein, we present a meta-analysis evaluating the efficacy and
      safety of nivolumab for previously treated advanced NSCLC patients. METHODS:
      Electronic databases were searched for eligible literature. Data of objective
      response rate (ORR), disease control rate, overall survival, progression-free
      survival, and adverse effects (AEs) were extracted and pooled. Outcomes analyzed
      and presented in this study were according to the original data from nivolumab 3
      mg/kg. RESULTS: In general, nine trials with 817 patients were included in this
      meta-analysis. The pooled ORR, disease control rate, 1-year overall survival
      rate, and 1-year progression-free survival rate were 20% (95% confidence interval
      [CI]: 17%-23%), 36% (95% CI: 22%-51%), 47% (95% CI: 40%-53%), 21% (95% CI: 18%
      24%), respectively. In addition, the rate of grade 3-4 AEs was only 8% (95% CI:
      6%-12%). Subgroup analysis showed no significant difference in terms of ORR
      between squamous and non-squamous NSCLC (odds ratio 1.23, 95% CI: 0.63-2.39,
      P=0.51). However, significantly greater ORR was presented in programmed cell
      death ligand 1 (PD-L1) positive cohort (ORR 31%, 95% CI: 24%-38%), compared to PD
      L1 negative cohort (ORR 12%, 95% CI: 9%-17%). The odds ratio for objective
      response to nivolumab in PD-L1 positive cases relative to negative cases was 3.08
      (95% CI: 1.87-5.08, P<0.0001). CONCLUSION: In conclusion, nivolumab is a
      promising second-line agent for previously treated advanced NSCLC with manageable
      AEs. Both squamous and non-squamous NSCLC patients showed similar efficacy. In
      addition, patients with positive PD-L1 expression had better response from
      nivolumab. MICROABSTRACT: We present a meta-analysis evaluating the efficacy and
      safety of nivolumab for previously treated advanced NSCLC patients. In our study,
      nivolumab is a promising second-line agent for previously treated advanced NSCLC
      with manageable AEs. Both squamous and non-squamous NSCLC patients showed similar
      efficacy. In addition, patients with positive PD-L1 expression had better
      response from nivolumab.

PMID- 27713641
TI  - Radiation dose reduction for patients with extranodal NK/T-cell lymphoma with
      complete response after initial induction chemotherapy.
AB  - Previous studies have found that radiotherapy (RT) dose less than 50 Gy resulted
      in inferior outcomes for early stage extranodal NK/T-cell lymphoma (ENKTL).
      Nowadays, induction chemotherapy (CT) followed by RT consolidation is often used.
      For patients who get complete response (CR) after CT, whether RT dose can be
      safely reduced or not remains unknown. This retrospective study compared the
      survival outcomes between patients who received higher dose (>50 Gy) and lower
      dose (<=50 Gy) RT after CR was attained by CT. One hundred and forty four
      patients of early stage ENKTL got CR after induction CT and received RT
      consolidation. Thirty-one patients received lower dose RT (median 46 Gy, range,
      36-50 Gy), and 113 patients received higher dose RT (median 56 Gy, range, 52-66
      Gy). In univariate survival analysis, age >60, local tumor invasion, and non
      asparaginase-based CT were associated with inferior progression-free survival
      (PFS) and overall survival (OS). However, there were no differences in PFS and OS
      between patients treated with higher and lower dose RT, which was confirmed in
      the multivariate survival analysis. Furthermore, reduced dose RT did not affect
      local control rate. Most common RT-related side effects were grade 1/2 mucositis
      and dermatitis, and the incidence rate of grade 3 mucositis or dermatitis was
      lower in patients treated with reduced dose RT (9.7% vs 15.0% for mucositis, and
      6.5% vs 17.7% for dermatitis). In conclusion, this study found that RT dose could
      be safely reduced without compromising survival outcomes and further improved RT
      related side effects. Prospective randomized controlled trials are warranted to
      validate our findings.

PMID- 27713642
TI  - Differential proteomics analysis of low- and high-grade of astrocytoma using
      iTRAQ quantification.
AB  - Astrocytoma is one of the most common types of brain tumor, which is
      histologically and clinically classified into four grades (I-IV): I (pilocytic
      astrocytoma), II (diffuse astrocytoma), III (anaplastic astrocytoma), and IV
      (glioblastoma multiforme). A higher grade astrocytoma represents a worse
      prognosis and is more aggressive. In this study, we compared the differential
      proteome profile of astrocytoma from grades I to IV. The protein samples from
      clinical specimens of grades I, II, III, and IV astrocytoma were analyzed by two
      dimensional liquid chromatography-tandem mass spectrometry and isobaric tags for
      relative and absolute quantitation and quantification. A total of 2,190 proteins
      were identified. Compared to grade I astrocytoma, 173 (12.4%), 304 (14%), and 462
      (21.2%) proteins were aberrantly expressed in grades II, III, and IV,
      respectively. By bioinformatics analysis, the cell proliferation, invasion, and
      angiogenesis-related pathways increase from low- to high-grade of astrocytoma.
      Five differentially expressed proteins were validated by Western blot. Within
      them, matrix metalloproteinase-9 and metalloproteinase inhibitor 1 were
      upregulated in glioblastoma multiforme group; whereas fibulin-2 and -5 were
      downregulated in grade II/III/IV astrocytoma, and the negative expression was
      significantly associated with advanced clinical stage. Functional analysis showed
      that both fibulin-2 and -5 may exert an antitumor effect by inhibiting cell
      proliferation, in vitro migration/invasion in glioma cells. New molecular
      biomarkers are likely to be used for accurate classification of astrocytoma and
      likely to be the target for drug development.

PMID- 27713643
TI  - Postoperative prophylactic hepatic arterial infusion chemotherapy for stage III
      colorectal cancer: a retrospective study.
AB  - BACKGROUND: Radical resection is the main treatment for colorectal cancer (CRC),
      but metastasis or recurrence is common in which liver metastasis accounted for
      83% of the cases. Therefore, the prognosis of patients with advanced CRC may be
      improved if liver metastasis is prevented. This study aims to investigate the
      efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of
      stage III CRC patients after curative resection. METHODS: Between 2002 and 2008,
      287 stage III CRC patients who had undergone radical resection were included in
      this study. According to postoperative adjuvant chemotherapy modality, these
      patients were divided into two groups. Patients in the combined therapy group
      received two cycles of HAIC plus four cycles of systemic chemotherapy, while
      patients in the monotherapy group received six cycles of systemic chemotherapy
      alone. The HAIC regimen consisted of hepatic arterial infusion of oxaliplatin
      (OXA, 85 mg/m2) on day 1 and 5-fluorouracil (5-FU, 2,400 mg/m2) on days 2 and 3
      followed by a vein infusion of folinic acid (FA, 200 mg/m2) as a 2-hour infusion
      on days 2 and 3. The systemic chemotherapy regimen consisted of a 2-hour infusion
      of OXA (85 mg/m2) on day 1 followed by FA (200 mg/m2) as a 2-hour infusion on
      days 2 and 3, and by 5-FU (2,400 mg/m2) as a 48-hour infusion. This was repeated
      every 4 weeks. All cases were followed up for 5 years or until death. The 5-year
      overall survival, disease-free survival, liver metastases-free survival, and the
      overall liver metastases rates were retrospectively compared. RESULTS:
      Significant differences were found in the 5-year overall survival (combined
      therapy, 70.71%; monotherapy, 57.14%; P=0.014), disease-free survival (combined
      therapy, 69.29%; monotherapy, 55.78%; P=0.021), and liver metastases-free
      survival rates (combined therapy, 70%; monotherapy, 56.46%; P=0.019). CONCLUSION:
      Prophylactic adjuvant HAIC can prevent metachronous liver metastases and improve
      the prognosis of patients with stage III CRC after curative resection.

PMID- 27713645
TI  - Evaluating vancomycin susceptibility in Staphylococcus aureus.

PMID- 27713644
TI  - Complications of ultrasound-guided percutaneous microwave ablation of renal cell
      carcinoma.
AB  - PURPOSE: To retrospectively review the complications of ultrasound (US)-guided
      percutaneous microwave ablation (MWA) of renal cell carcinoma. PATIENTS AND
      METHODS: In this study, 101 patients with 105 tumors seen from April 2006 to Feb
      2014 were enrolled retrospectively. The patients were treated with US-guided
      percutaneous MWA and were followed up with contrast-enhanced US and computed
      tomography or magnetic resonance imaging at 1, 3, and 6 months and every 6 months
      thereafter. RESULTS: Technical success was achieved in 99 of 105 tumors (94.3%).
      The median follow-up time was 25 (range 1.13-93.23) months. Among the 105 tumors,
      26 complications in 24.8% of patients and 23 minor complications (Clavien-Dindo
      Grades I and II) in 21.9% of patients were noted, accounting for 88.5% of all
      complications. All the minor complications were cured. Three major complications
      (Clavien-Dindo Grade >=III) occurred in 2.9% of the patients, accounting for
      11.5% of all complications: hydrothorax in two patients and bowel injury in one.
      The two patients who had hydrothorax post-MWA had a history of cirrhosis and were
      treated with catheter drainage. The bowel injury was treated surgically. In all
      patients, the changes in serum creatinine and urea nitrogen levels from before to
      after the procedure were small. CONCLUSION: US-guided percutaneous MWA is a
      beneficial treatment for renal cell carcinoma in selected patients; however, if
      the renal tumor is close to the bowel, or the patient has serious comorbidities
      or has undergone abdominal surgery, the procedure must be performed more
      carefully.

PMID- 27713646
TI  - Cost-effectiveness analysis of fesoterodine flexible dose in newly diagnosed
      patients with overactive bladder in routine clinical practice in Spain.
AB  - OBJECTIVE: To carry out cost-effectiveness analysis from the Spanish National
      Health System perspective, of treating overactive bladder (OAB), in newly
      diagnosed patients with two flexible doses of fesoterodine in routine clinical
      practice. PATIENTS AND METHODS: Economic evaluation of flexible-dose fesoterodine
      in newly diagnosed patients, including two treatment groups: standard escalating
      from 4 to 8 mg or fast escalating to 8 mg. Costs were estimated from health care
      resources utilization related to OAB, and were expressed in 2015 Euros. Quality
      adjusted life-years (QALYs) were obtained from overactive bladder questionnaire
      short form. Univariate and probabilistic sensitivity analyses were carried out.
      RESULTS: Three hundred and ninety symptomatic OAB patients treated with
      fesoterodine and newly diagnosed (141 in fast escalating group and 249 in
      standard escalating) were analyzed. Adjusted health care total costs were not
      statistically different; difference -?4.1 (confidence interval: -153.3; 25.1)
      P=0.842. QALYs were higher in fast escalating to high dose vs standard escalating
      group, resulting in a cost of -?16,020/QALY gained for fast escalating vs
      standard escalating group. CONCLUSION: When the cost-effectiveness threshold is
      set at a maximum value of ?30,000/QALY gained, fesoterodine fast escalating group
      was cost-effective vs standard escalating group 67.6% of the time. The treatment
      with fesoterodine, in female patients newly diagnosed, fast escalating to 8 mg
      was a cost-effective option relative to escalating traditionally from 4 to 8 mg,
      in the management of OAB in routine clinical practice, from the Spanish National
      Health System perspective.

PMID- 27713647
TI  - Efficacy and tolerance of an injectable medical device containing stable hybrid
      cooperative complexes of high- and low-molecular-weight hyaluronic acid: a
      monocentric 16 weeks open-label evaluation.
AB  - BACKGROUND: An injectable medical device containing stable hybrid cooperative
      complexes of high- and low-molecular-weight hyaluronic acid (HA) has been
      developed with characteristics suited for a global improvement of facial
      esthetics. OBJECTIVE: To evaluate the HA product performance in improving some
      key facial esthetic features. The study employed clinical scales, subjective
      evaluations, and facial skin objective measurements. METHODS: A single Italian
      site treated 64 female subjects aged 38-60 years, with injections at five
      predetermined points, on each side of the face, with a 4-week time lapse between
      the first and the second product administration. Subjects were evaluated after 4,
      8, 12, and 16 weeks, using validated clinical scales, subjective evaluation, and
      objective quantitative outcome measures. Assessment of esthetic results included
      photographic documentation. RESULTS: Both the clinical and subjective
      assessments, and the majority of objective instrumental parameters indicated an
      improvement throughout the study and were already significant at week 4 or 8 and
      were still significant at week 16 (3 months after the second treatment). Minor
      and temporary local skin reactions were observed in 23% of subjects at the site
      of the injections, and the global judgment on tolerability was good or excellent,
      both in the investigators' opinion and volunteers' self-evaluation. CONCLUSION:
      Both subjective and objective improvement of the facial parameters was consistent
      with the bio-remodeling purpose, and persistent and still statistically
      significant at the end of the study. The tolerability and safety profile of the
      product were judged good or excellent both by investigators and volunteers. This
      study supports the claim for bio-remodeling of these stable hybrid cooperative
      complexes of low- and high-molecular-weight HA.

PMID- 27713649
TI  - Smartphone applications for chronic pain management: a critical appraisal.

PMID- 27713648
TI  - A novel paradigm to evaluate conditioned pain modulation in fibromyalgia.
AB  - INTRODUCTION: Application of noxious stimulation to one body area reduces pain
      sensitivity in a remote body area through activation of an endogenous pain
      inhibitory network, a behavioral phenomenon referred to as conditioned pain
      modulation (CPM). The efficiency of CPM is predictive of a variety of health
      outcomes, while impaired CPM has been associated with various chronic pain
      conditions. Current methods used to assess CPM vary widely, and interest in CPM
      method development remains strong. Here, we evaluated a novel method for
      assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb
      pressure as both a test and conditioning stimulus. METHODS: Sixteen female FM
      patients and 14 matched healthy controls underwent CPM testing with thumbnail
      pressure as the test stimulus, and either cold water or noxious pressure as the
      conditioning stimulus. CPM magnitude was evaluated as the difference in pain
      rating of the test stimulus applied before and during the conditioning stimulus.
      RESULTS: In healthy controls, application of either pressure or cold water
      conditioning stimulation induced CPM as evidenced by a significant reduction in
      test stimulus pain rating during conditioning (P=0.007 and P=0.021,
      respectively). In contrast, in FM patients, neither conditioning stimulus induced
      a significant CPM effect (P>0.274). There was a significant difference in CPM
      magnitude for FM patients compared to healthy controls with noxious pressure
      conditioning stimulation (P=0.023); however, no significant difference in CPM was
      found between groups using cold water as a conditioning stimulus (P=0.269).
      CONCLUSION: The current study demonstrates that thumbnail pressure can be used as
      both a test and conditioning stimulus in the assessment of CPM. This study
      further confirms previous findings of attenuated CPM in FM patients compared with
      healthy controls.

PMID- 27713650
TI  - Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South
      African type 2 diabetic subjects.
AB  - AIM: To determine the effective dose of glibenclamide by quantifying the dose
      response relationship in South African type 2 diabetic patients. PATIENTS AND
      METHODS: A total of 24 type 2 diabetic patients participated in a glibenclamide
      dose-escalation study during which glibenclamide, glucose, and insulin
      concentrations were quantified, while the dose of glibenclamide was progressively
      increased. All except four subjects contributed data on all dose-escalation
      steps; however, data from all 24 patients were included in the model-based
      analysis. Pharmacokinetic/pharmacodynamic (PKPD) relationships were modeled using
      the software Nonmem(r). Six models were utilized to explore the effect of
      alternative glibenclamide dose and plasma concentration inputs on various metrics
      of glucose response. RESULTS: Six models adequately described the experimental
      data. The effective dose for a glucose-lowering effect suggested by PKPD modeling
      is less than 5 mg/day. Doses beyond 5 mg/day do not meaningfully add to
      glibenclamide effects on blood-glucose response. CONCLUSION: The effective dose
      of glibenclamide, suggested by PKPD modeling, is less than 5 mg/day. Higher doses
      of glibenclamide, eg, 15 mg/day as originally recommended by the manufacturer, do
      not produce further decrease in the blood glucose level but may predispose the
      patients to adverse effects.

PMID- 27713651
TI  - Quality of life and use of health care resources among patients with chronic
      depression.
AB  - PURPOSE: This study estimates the health-related quality of life and the health
      care resource utilization of patients diagnosed with chronic depression (CD) in
      Spain. PATIENTS AND METHODS: We used the Spanish National Health Survey 2011
      2012, a cross-sectional survey representative at the national level, that selects
      people aged between 18 and 64 years (n=14,691). We estimated utility indices
      through the EuroQol five-dimensional descriptive system questionnaire included in
      the survey. We calculated percentage use of health care resources (medical
      visits, hospitalizations, emergency services, and drug consumption) and average
      number of resources used when available. A systematic comparison was made between
      people diagnosed with CD and other chronic conditions (OCCs). The chi-square
      test, Mann-Whitney U-test, and Kruskal-Wallis test were used to determine the
      statistical significance of differences between comparison groups. Multivariate
      analyses (Poisson regression, logistic regression, and linear regression) were
      also carried out to assess the relationship between quality of life and
      consumption of health care resources. RESULTS: Approximately, 6.1% of the
      subjects aged between 18 and 64 years were diagnosed with CD (average age 48.3+/
      11 years, 71.7% females). After controlling for age, sex, and total number of
      comorbidities, a diagnosis of CD reduced utility scores by 0.09 (P<0.05) vs OCCs,
      and increased the average number of hospitalizations by 15%, the average number
      of days at hospital by 51%, and the average number of visits to emergency
      services by 15% (P<0.05). CD also increased the average number of visits to
      secondary care by 14% and visits to general practitioners by 4%. People with CD
      had a higher probability of consuming drugs than people with OCCs (odds ratio
      [OR]: 1.24, P<0.05), but only 38.6% took antidepressants. CONCLUSION: People with
      CD had significantly lower health-related quality of life than people with OCCs.
      CD was associated with increased hospital length of stay and involved a higher
      consumption of emergency services and drugs than OCCs.

PMID- 27713653
TI  - The use of cognitive behavioral therapy-based coping strategies in dealing with
      examination-related stress at medical school.

PMID- 27713652
TI  - Acquired hypofibrinogenemia: current perspectives.
AB  - Acquired hypofibrinogenemia is most frequently caused by hemodilution and
      consumption of clotting factors. The aggressive replacement of fibrinogen has
      become one of the core principles of modern management of massive hemorrhage. The
      best method for determining the patient's fibrinogen level remains controversial,
      and particularly in acquired dysfibrinogenemia, could have major therapeutic
      implications depending on which quantification method is chosen. This review
      introduces the available laboratory and point-of-care methods and discusses the
      relative advantages and limitations. It also discusses current strategies for the
      correction of hypofibrinogenemia.

PMID- 27713654
TI  - Iterative learning control with applications in energy generation, lasers and
      health care.
AB  - Many physical systems make repeated executions of the same finite time duration
      task. One example is a robot in a factory or warehouse whose task is to collect
      an object in sequence from a location, transfer it over a finite duration, place
      it at a specified location or on a moving conveyor and then return for the next
      one and so on. Iterative learning control was especially developed for systems
      with this mode of operation and this paper gives an overview of this control
      design method using relatively recent relevant applications in wind turbines,
      free-electron lasers and health care, as exemplars to demonstrate its
      applicability.

PMID- 27713655
TI  - Quantifying uncertainty in partially specified biological models: how can optimal
      control theory help us?
AB  - Mathematical models in biology are highly simplified representations of a complex
      underlying reality and there is always a high degree of uncertainty with regards
      to model function specification. This uncertainty becomes critical for models in
      which the use of different functions fitting the same dataset can yield
      substantially different predictions-a property known as structural sensitivity.
      Thus, even if the model is purely deterministic, then the uncertainty in the
      model functions carries through into uncertainty in model predictions, and new
      frameworks are required to tackle this fundamental problem. Here, we consider a
      framework that uses partially specified models in which some functions are not
      represented by a specific form. The main idea is to project infinite dimensional
      function space into a low-dimensional space taking into account biological
      constraints. The key question of how to carry out this projection has so far
      remained a serious mathematical challenge and hindered the use of partially
      specified models. Here, we propose and demonstrate a potentially powerful
      technique to perform such a projection by using optimal control theory to
      construct functions with the specified global properties. This approach opens up
      the prospect of a flexible and easy to use method to fulfil uncertainty analysis
      of biological models.

PMID- 27713656
TI  - Unifying dynamical and structural stability of equilibria.
AB  - We exhibit a fundamental relationship between measures of dynamical and
      structural stability of linear dynamical systems-e.g. linearized models in the
      vicinity of equilibria. We show that dynamical stability, quantified via the
      response to external perturbations (i.e. perturbation of dynamical variables),
      coincides with the minimal internal perturbation (i.e. perturbations of
      interactions between variables) able to render the system unstable. First, by
      reformulating a result of control theory, we explain that harmonic external
      perturbations reflect the spectral sensitivity of the Jacobian matrix at the
      equilibrium, with respect to constant changes of its coefficients. However, for
      this equivalence to hold, imaginary changes of the Jacobian's coefficients have
      to be allowed. The connection with dynamical stability is thus lost for real
      dynamical systems. We show that this issue can be avoided, thus recovering the
      fundamental link between dynamical and structural stability, by considering
      stochastic noise as external and internal perturbations. More precisely, we
      demonstrate that a linear system's response to white-noise perturbations directly
      reflects the intensity of internal white-noise disturbance that it can
      accommodate before becoming stochastically unstable.

PMID- 27713657
TI  - Thin-film electrodes for high-capacity lithium-ion batteries: influence of phase
      transformations on stress.
AB  - In this study, we revisit experiments by Sethuraman et al. (2010 J. Power
      Sources, 195, 5062-5066. (doi:10.1016/j.jpowsour.2010.02.013)) on the stress
      evolution during the lithiation/delithiation cycle of a thin film of amorphous
      silicon. Based on recent work that show a two-phase process of lithiation of
      amorphous silicon, we formulate a phase-field model coupled to elasticity in the
      framework of Larche-Cahn. Using an adaptive nonlinear multigrid algorithm for the
      finite-volume discretization of this model, our two-dimensional numerical
      simulations show the formation of a sharp phase boundary between the lithiated
      and the amorphous silicon that continues to move as a front through the thin
      layer. We show that our model captures the non-monotone stress loading curve and
      rate dependence, as observed in recent experiments and connects characteristic
      features of the curve with the structure formation within the layer. We take
      advantage of the thin film geometry and study the corresponding one-dimensional
      model to establish the dependence on the material parameters and obtain a
      comprehensive picture of the behaviour of the system.

PMID- 27713658
TI  - The Green's functions for peridynamic non-local diffusion.
AB  - In this work, we develop the Green's function method for the solution of the
      peridynamic non-local diffusion model in which the spatial gradient of the
      generalized potential in the classical theory is replaced by an integral of a
      generalized response function in a horizon. We first show that the general
      solutions of the peridynamic non-local diffusion model can be expressed as
      functionals of the corresponding Green's functions for point sources, along with
      volume constraints for non-local diffusion. Then, we obtain the Green's functions
      by the Fourier transform method for unsteady and steady diffusions in infinite
      domains. We also demonstrate that the peridynamic non-local solutions converge to
      the classical differential solutions when the non-local length approaches zero.
      Finally, the peridynamic analytical solutions are applied to an infinite plate
      heated by a Gauss source, and the predicted variations of temperature are
      compared with the classical local solutions. The peridynamic non-local diffusion
      model predicts a lower rate of variation of the field quantities than that of the
      classical theory, which is consistent with experimental observations. The
      developed method is applicable to general diffusion-type problems.

PMID- 27713659
TI  - Stress concentration in periodically rough Hertzian contact: Hertz to soft-flat
      punch transition.
AB  - We report on the elastic contact between a spherical lens and a patterned
      substrate, composed of a hexagonal lattice of cylindrical pillars. The stress
      field and the size of the contact area are obtained by means of numerical
      methods: a superposition method of discrete pressure elements and an iterative
      bisection-like method. For small indentations, a transition from a Hertzian to a
      soft-flat-punch behaviour is observed when the surface fraction of the substrate
      that is covered by the pillars is increased. In particular, we present a master
      curve defined by two dimensionless parameters, which allows one to predict the
      stress at the centre of the contact region in terms of the surface fraction
      occupied by pillars. The transition between the limiting contact regimes,
      Hertzian and soft-flat-punch, is well described by a rational function.
      Additionally, a simple model to describe the Boussinesq-Cerruti-like contact
      between the lens and a single elastic pillar, which takes into account the pillar
      geometry and the elastic properties of the two bodies, is presented.

PMID- 27713661
TI  - [Formula: see text]-symmetric graphene under a magnetic field.
AB  - We propose a [Formula: see text]-symmetrically deformed version of the graphene
      tight-binding model under a magnetic field. We analyse the structure of the
      spectra and the eigenvectors of the Hamiltonians around the K and K' points, both
      in the [Formula: see text]-symmetric and [Formula: see text]-broken regions. In
      particular, we show that the presence of the deformation parameter V produces
      several interesting consequences, including the asymmetry of the zero-energy
      states of the Hamiltonians and the breakdown of the completeness of the
      eigenvector sets. We also discuss the biorthogonality of the eigenvectors, which
      turns out to be different in the [Formula: see text]-symmetric and [Formula: see
      text]-broken regions.

PMID- 27713660
TI  - The interface of SrTiO3 and H2O from density functional theory molecular
      dynamics.
AB  - We use dispersion-corrected density functional theory molecular dynamics
      simulations to predict the ionic, electronic and vibrational properties of the
      SrTiO3/H2O solid-liquid interface. Approximately 50% of surface oxygens on the
      planar SrO termination are hydroxylated at all studied levels of water coverage,
      the corresponding number being 15% for the planar TiO2 termination and 5% on the
      stepped TiO2-terminated surface. The lateral ordering of the hydration structure
      is largely controlled by covalent-like surface cation to H2O bonding and surface
      corrugation. We find a featureless electronic density of states in and around the
      band gap energy region at the solid-liquid interface. The vibrational spectrum
      indicates redshifting of the O-H stretching band due to surface-to-liquid
      hydrogen bonding and blueshifting due to high-frequency stretching vibrations of
      OH fragments within the liquid, as well as strong suppression of the OH
      stretching band on the stepped surface. We find highly varying rates of proton
      transfer above different SrTiO3 surfaces, owing to differences in hydrogen bond
      strength and the degree of dissociation of incident water. Trends in proton
      dynamics and the mode of H2O adsorption among studied surfaces can be explained
      by the differential ionicity of the Ti-O and Sr-O bonds in the SrTiO3 crystal.

PMID- 27713662
TI  - Decadal variability of extreme wave height representing storm severity in the
      northeast Atlantic and North Sea since the foundation of the Royal Society.
AB  - Long-term estimation of extreme wave height remains a key challenge because of
      the short duration of available wave data, and also because of the possible
      impact of climate variability on ocean waves. Here, we analyse storm-based
      statistics to obtain estimates of extreme wave height at locations in the
      northeast Atlantic and North Sea using the NORA10 wave hindcast (1958-2011), and
      use a 5 year sliding window to examine temporal variability. The decadal
      variability is correlated to the North Atlantic oscillation and other atmospheric
      modes, using a six-term predictor model incorporating the climate indices and
      their Hilbert transforms. This allows reconstruction of the historic extreme
      climate back to 1661, using a combination of known and proxy climate indices.
      Significant decadal variability primarily driven by the North Atlantic
      oscillation is observed, and this should be considered for the long-term
      survivability of offshore structures and marine renewable energy devices. The
      analysis on wave climate reconstruction reveals that the variation of the mean,
      99th percentile and extreme wave climates over decadal time scales for locations
      close to the dominant storm tracks in the open North Atlantic are comparable,
      whereas the wave climates for the rest of the locations including the North Sea
      are rather different.

PMID- 27713663
TI  - Edge wrinkling in elastically supported pre-stressed incompressible isotropic
      plates.
AB  - The equations governing the appearance of flexural static perturbations at the
      edge of a semi-infinite thin elastic isotropic plate, subjected to a state of
      homogeneous bi-axial pre-stress, are derived and solved. The plate is
      incompressible and supported by a Winkler elastic foundation with, possibly,
      wavenumber dependence. Small perturbations superposed onto the homogeneous state
      of pre-stress, within the three-dimensional elasticity theory, are considered. A
      series expansion of the plate kinematics in the plate thickness provides a
      consistent expression for the second variation of the potential energy, whose
      minimization gives the plate governing equations. Consistency considerations
      supplement a constraint on the scaling of the pre-stress so that the classical
      Kirchhoff-Love linear theory of pre-stretched elastic plates is retrieved.
      Moreover, a scaling constraint for the foundation stiffness is also introduced.
      Edge wrinkling is investigated and compared with body wrinkling. We find that the
      former always precedes the latter in a state of uni-axial pre-stretch, regardless
      of the foundation stiffness. By contrast, a general bi-axial pre-stretch state
      may favour body wrinkling for moderate foundation stiffness. Wavenumber
      dependence significantly alters the predicted behaviour. The results may be
      especially relevant to modelling soft biological materials, such as skin or
      tissues, or stretchable organic thin-films, embedded in a compliant elastic
      matrix.

PMID- 27713664
TI  - Mathematical and numerical framework for metasurfaces using thin layers of
      periodically distributed plasmonic nanoparticles.
AB  - In this paper, we derive an impedance boundary condition to approximate the
      optical scattering effect of an array of plasmonic nanoparticles mounted on a
      perfectly conducting plate. We show that at some resonant frequencies the
      impedance blows up, allowing for a significant reduction of the scattering from
      the plate. Using the spectral properties of a Neumann-Poincare type operator, we
      investigate the dependency of the impedance with respect to changes in the
      nanoparticle geometry and configuration.

PMID- 27713665
TI  - The interactive bending wrinkling behaviour of inflated beams.
AB  - A model is proposed based on a Fourier series method to analyse the interactive
      bending wrinkling behaviour of inflated beams. The whole wrinkling evolution is
      tracked and divided into three stages by identifying the bifurcations of the
      equilibrium path. The critical wrinkling and failure moments of the inflated beam
      can then be predicted. The global-local interactive buckling pattern is
      elucidated by the proposed theoretical model and also verified by non-contact
      experimental tests. The effects of geometric parameters, internal pressure and
      boundary conditions on the buckling of inflated beams are investigated finally.
      The results reveal that the interactive buckling characteristics of an inflated
      beam under bending are more sensitive to the dimensions of the structure and
      boundary conditions. We find that for beams which are simply supported at both
      ends or clamped and simply supported, boundary conditions may prevent the
      wrinkling formation. The results provide significant support for our
      understanding of the bending wrinkling behaviour of inflated beams.

PMID- 27713666
TI  - Pipette aspiration testing of soft tissues: the elastic half-space model
      revisited.
AB  - The pipette aspiration testing technique is considered, and the elastic half
      space model, which was originally introduced in the isotropic incompressible
      case, is revisited and generalized for the case of transverse isotropy.
      Asymptotic solutions are obtained in the two limiting cases of a wide and a
      narrow pipette.

PMID- 27713667
TI  - Polyelectrolyte-graphene Nanocomposites for Biosensing Applications.
AB  - Due to their unique structure, the optical and mechanical properties graphene and
      its derivatives (e.g. graphene oxide, reduced graphene oxide) have captured the
      attention of a constantly increasing number of scientists with regards to
      biomolecule sensing. This mini review focuses on one specific type of sensor,
      that consisting of graphene and polyelectrolytes. Polyelectrolyte-graphene
      nanocomposites exhibit outstanding detection capabilities by synergistically
      combining the characteristics of both components, outperforming traditional
      sensors in many cases. Characteristics and mechanistic details of the most
      important polyelectrolyte-graphene based sensors will be discussed in detail in
      addition to some current challenges and future perspectives.

PMID- 27713668
TI  - Interventions for improving adherence to iron chelation therapy in people with
      sickle cell disease or thalassaemia.
AB  - This is the protocol for a review and there is no abstract. The objectives are as
      follows: To identify and assess the effectiveness of interventions to improve
      adherence to iron chelation therapy compared to standard care in people with SCD
      or thalassaemia including: identifying and assessing the effectiveness of
      different types of interventions (psychological and psychosocial, educational,
      medication interventions, or multi-component interventions);identifying and
      assessing the effectiveness of interventions specific to different age groups
      (children, adolescents, adults).

PMID- 27713669
TI  - Exploring Service Provider Perceptions of Treatment Barriers Facing Black, Non
      Gay-Identified MSMW.
AB  - Non-gay-identified men who have sex with men and women and who use alcohol and
      other drugs are a vulnerable population. Little is known about health and medical
      service provider interaction with these underserved clients. This article
      presents a thematic analysis of two focus groups undertaken with social and
      medical service providers regarding the needs of non-gay-identified men who have
      sex with men and women. Four emergent themes (labeling, constructions of
      masculinity, HIV/AIDS awareness, and treatment success) illustrate perceived
      barriers to HIV/AIDS prevention and treatment, as well as treatment success.
      Implications for policy, practice, and future research are discussed.

PMID- 27713670
TI  - Calprotectin: Clinical Applications in Pediatrics.
AB  - As seen over the past 20 years, calprotectin has evolved as a novel, non-invasive
      biomarker of gastrointestinal (GI) inflammation. We present this review of
      calprotectin in pediatrics. This article will focus on studies using calprotectin
      concentrations from different body fluids to monitor inflammation in different
      disease states and conditions. The ultimate goal of our group is to lay down a
      foundation as we consider using calprotectin prospectively as a marker of
      intestinal inflammation that could lead to further testing and possibly a marker
      of preparedness for feeding. We surveyed all published studies in English of
      calprotectin in neonates, infants, children, and adolescents through February
      2014. We will discuss calprotectin's basic properties and analysis such as
      characteristics, identification, presence in body fluids, and maturational
      development. In addition, calprotectin's use in inflammatory diseases exploring
      both GI and non-GI conditions will be evaluated and compared with other serum
      markers presently available. Finally, a summary of our findings and discussion of
      future work that could be undertaken in order to render calprotectin as a more
      useful monitoring tool to the medical research community will complete the
      review.

PMID- 27713671
TI  - Stability and Sterility of Enoxaparin 8 mg/mL Subcutaneous Injectable Solution.
AB  - BACKGROUND: Enoxaparin is often diluted to accurately deliver doses to neonatal
      and infant patients. Current recommendations for dilutions may not be adequate
      for the smallest patients. METHODS: Review of dosing at our institution occurred,
      and an 8 mg/mL concentration of enoxaparin was chosen. A concentration of 8 mg/mL
      was compounded by diluting 0.4 mL of enoxaparin (100 mg/mL) into 4.6 mL of
      sterile water for injection into an empty sterile vial. Four syringes of the 8
      mg/mL concentration were prepared by 5 technicians (20 total syringes). Stability
      and sterility testing occurred a 0, 7, 14, and 30 days. One-way repeated-measures
      analysis of variance was used to detect significant differences in Anti-Factor Xa
      concentrations at the testing time points. RESULTS: The dilution of enoxaparin
      was sterile at 30 days but exhibited significant degradation at the 30-day point
      (p < 0.05). CONCLUSION: A dilution of enoxaparin 8 mg/mL is stable and sterile
      for 14 days refrigerated but is not stable at 30 days.

PMID- 27713672
TI  - Outcomes in Postoperative Pediatric Cardiac Surgical Patients Who Received an
      Antiepileptic Drug.
AB  - BACKGROUND: Advances in cardiac operations over the last few decades, including
      corrective operations in early life, have dramatically increased the survival of
      children with congenital heart disease. However, postoperative care has been
      associated with neurologic complications, with seizures being the most common
      manifestation. The primary objective of this study is to describe the outcomes in
      pediatric patients who received an antiepileptic drug (AED) post-cardiac surgery.
      METHOD: A retrospective cohort study was performed in all patients less than 18
      years of age who received an AED in the cardiovascular intensive care unit at
      Texas Children's Hospital from June 2002 until June 2012. Cardiac surgical
      patients initiated on phenobarbital, phenytoin, and levetiracetam were queried.
      Patients were excluded if the AED was not initiated on the admission for surgery.
      Patients who received 1 AED were compared to patients who received 2 AED, and
      differences in outcomes examined between the 3 AEDs used were evaluated. RESULTS:
      A total of 37 patients met the study criteria. Patients were initiated on an AED
      a median of 4 days following surgery and became seizure free a median of 1 day
      after initiation, with 65% remaining seizure free after the first dose. Half of
      all patients required 2 AEDs for seizure control, with a higher proportion of
      adolescents requiring 2 AEDs (p = 0.04). No differences were found when comparing
      the collected outcomes between phenobarbital, fosphenytoin, or levetiracetam.
      CONCLUSION: No adverse events were reported with the AEDs reviewed. Further work
      is necessary to evaluate long-term neurodevelopmental outcomes in this population
      and whether outcomes are a result of the AED or of other clinical sequelae.

PMID- 27713673
TI  - Does Combination Therapy With Vancomycin and Piperacillin-Tazobactam Increase the
      Risk of Nephrotoxicity Versus Vancomycin Alone in Pediatric Patients?
AB  - OBJECTIVES: To determine if the incidence of nephrotoxicity is higher in
      pediatric patients treated with the combination of vancomycin and piperacillin
      tazobactam, compared to patients treated with vancomycin alone. Secondary
      objectives were to determine if admission to an intensive care unit (ICU), higher
      serum vancomycin trough concentrations (>15 mg/L), or receipt of other
      nephrotoxic agents were related to the development of nephrotoxicity. METHODS:
      This was a retrospective, single-center, cohort study of 79 patients treated with
      vancomycin and 106 patients treated with vancomycin and pipracillin/tazobacatam
      (TZP). Serum creatinine was trended to determine if patients had nephrotoxicity,
      which was defined as at least a 100% increase in serum creatinine or an increase
      of >=0.5 mg/dL from the baseline value. Fisher's exact test was used to compare
      the incidence of nephrotoxicity in the vancomycin group to the combination group.
      Secondary objectives were evaluated by using relative risk (RR). RESULTS:
      Nephrotoxicity developed in 3 of 79 patients (3.8%) in the vancomycin group and
      in 25 of 106 patients (23.6%) on combination therapy (p = 0.0001). In patients
      receiving only vancomycin, there was no statistically significant increase in
      nephrotoxicity for patients in the ICU (RR 1.85, 95% confidence interval [CI]
      0.175-19.62, p = 0.61), those with higher vancomycin troughs (RR 2.32, CI 0.226
      23.86, p = 0.48), or those receiving other nephrotoxic medications (RR 2.94, CI
      0.2779-31.05, p = 0.37). In the combination group, having higher serum vancomycin
      trough concentrations increased the risk of nephrotoxicity (RR 5.22, CI 2.407
      11.306, p < 0.0001). CONCLUSIONS: Combination therapy with vancomycin and TZP is
      potentially more nephrotoxic than vancomycin alone. ICU admissions, high
      vancomycin troughs (>15 mg/L), and concomitant nephrotoxic medications cannot be
      excluded as risk factors for the observed increase in nephrotoxicity in patients
      receiving vancomycin and TZP.

PMID- 27713674
TI  - Impact of Computerized Provider Order Entry on Total Parenteral Nutrition in the
      Neonatal Intensive Care Unit.
AB  - OBJECTIVES: To determine if computerized provider order entry (CPOE)
      implementation impacts the time it takes for preterm neonates to reach their
      parenteral macronutrient goals. METHODS: Retrospective review of neonates <1750 g
      receiving parenteral nutrition (PN) before and after the implementation of CPOE.
      Primary outcome was the attainment of parenteral macronutrient goals. Secondary
      outcomes included time to attainment, the frequency of electrolyte abnormalities,
      and the incidence of required adjustments made to PN orders by verification
      pharmacists. RESULTS: Goal PN was achieved by 12/47 (25.5%) intervention vs. 2/44
      (4.5%) control group infants (p < 0.05). This goal was attained in 10.8 +/- 7.5
      days in the intervention group and 10 +/- 4.2 days in the control group (p =
      0.90). Goal protein was reached by 74.5% of CPOE patients vs. 36.4% of controls,
      p < 0.05. Lipid goals were achieved by 98% vs. 100% (p = 0.33) of patients and
      were attained at an average of 1.5 +/- 0.8 days vs. 2.0 +/- 1.1 days (p < 0.05).
      Abnormal serum electrolyte values occurred more frequently in the control group
      (0.79 vs. 1.12/day PN). Adjustments by a verification pharmacist were required in
      5.6% of CPOE compared with 30.4% of control group orders (p < 0.05). CONCLUSIONS:
      CPOE parenteral nutrition increased the proportion of preterm neonates attaining
      overall macronutrient goals. With CPOE, protein goals were reached by more
      patients and goal lipids were achieved faster. This system also decreased the
      number of pharmacist interventions during verification of PN orders and appeared
      to positively impact the incidence of serum electrolyte disturbances.

PMID- 27713675
TI  - Pharmacist-Led Model to Reduce Hospital Readmissions in Medically Complex
      Children.
AB  - OBJECTIVES: This pilot study investigated the feasibility and effect on health
      care utilization of medically complex children participating in a pharmacist-led
      model for care coordination. Quality of life and satisfaction with care were
      secondarily assessed for each patient. METHODS: Four medically complex children
      were enrolled and contacted by the pharmacist weekly for 5 consecutive months.
      Time for each encounter with a patient was collected. Each patient's hospital
      admissions, days of stay, emergency department visits, and clinic visits were
      recorded. At enrollment and at the end of the study, each caregiver completed the
      PedsQL 4.0 questionnaire to evaluate the child's quality of life and the Patient
      Assessment of Care for Chronic Conditions questionnaire to assess satisfaction
      with care. Patients aged 5 years and older completed an age-appropriate version
      of the PedsQL 4.0 as well. RESULTS: The pharmacist spent on average 60 to 80
      minutes per patient per week. Hospital admissions and days of stay decreased for
      3 patients and increased for 1 patient during this study. Quality of life
      increased for 2 patients and decreased for 2 patients and satisfaction with care
      increased for all 4 caregivers. CONCLUSIONS: This model was feasible for a
      pharmacist to coordinate and required frequent physician involvement. Health care
      utilization varied between patients, but overall decreased for the 4 patients
      pooled. Changes in quality of life varied and may be attributed to using a survey
      that was not specific to medically complex children. Overall, caregivers were
      highly satisfied with this service and the health care their child received.

PMID- 27713676
TI  - Meropenem-Induced Neutropenia in a Neonate.
AB  - Postmarketing surveillance has associated meropenem with the development of
      hematologic abnormalities, including agranulocytosis, neutropenia, and
      leukopenia, but the exact incidence in children is unknown. The case describes a
      full-term, 26-day-old neonate admitted for a sepsis workup. She was found to have
      a blood culture positive for Enterobacter cloacae and suspected meningitis and
      was initiated on meropenem 40 mg/kg/dose intravenously every 8 hours. On day 14
      of antibiotic treatment, the patient developed an isolated neutropenia with an
      absolute neutrophil count of 288 cells/mm3. Meropenem was discontinued on
      hospital day 20, and a follow-up complete blood cell count 2 months later
      confirmed resolution of the hematologic abnormality. Clinicians should monitor
      complete blood cell counts diligently in children who receive large doses and
      prolonged courses of meropenem.

PMID- 27713678
TI  - Correspondence.

PMID- 27713677
TI  - Intraoperative Anaphylactic Reaction: Is it the Floseal?
AB  - When hemodynamic or respiratory instability occurs intraoperatively, the inciting
      event must be determined so that a therapeutic plan can be provided to ensure
      patient safety. Although generally uncommon, one cause of cardiorespiratory
      instability is anaphylactic reactions. During anesthetic care, these most
      commonly involve neuromuscular blocking agents, antibiotics, or latex. Floseal is
      a topical hemostatic agent that is frequently used during orthopedic surgical
      procedures to augment local coagulation function and limit intraoperative blood
      loss. As these products are derived from human thrombin, animal collagen, and
      animal gelatin, allergic phenomenon may occur following their administration. We
      present 2 pediatric patients undergoing posterior spinal fusion who developed
      intraoperative hemodynamic and respiratory instability following use of the
      topical hemostatic agent, Floseal. Previous reports of such reactions are
      reviewed, and the perioperative care of patients with intraoperative anaphylaxis
      is discussed.

PMID- 27713679
TI  - PPAG INDUCTS NEW FELLOWS.

PMID- 27713680
TI  - The influence of drinking motives on hookah use frequency among young multi
      substance users.
AB  - PURPOSE: The present work examined the influence of drinking motives on hookah
      use frequency among individuals reporting both alcohol and hookah use (multi
      substance users). Despite growing documentation of cross-substance effects
      between motives and substance use, limited research has examined these
      relationships specifically with respect to hookah use. METHODS: Participants were
      134 (75.37% female) hookah and alcohol users, aged 18-47 years (M = 22.17, SD =
      3.66) who completed measures of substance use, drinking motives, and reported
      demographic information. Structural equation modeling (SEM) was employed to
      investigate the predictive value of drinking motives on hookah use frequency, age
      taken into account. RESULTS: Findings showed that hookah use was negatively
      associated with age (beta = -.22, p <= .01). The model regressing hookah use on
      the four drinking motives provided adequate fit (chi2 = 314.31, df = 180, p <
      .05, CFI = .92, RMSEA = .075 [95% CI, .06-.09]). Hookah use was associated
      negatively with social motives (beta = -.43, p < .001) and positively with
      conformity motives (beta = .24, p <= .05). CONCLUSIONS: These findings are
      consistent with multi-substance use literature suggesting that drinking motives
      are associated with the use of other substances, including increased hookah use
      frequency. Additional examinations of cross-substance cognitive processes are
      needed, particularly with respect to understanding whether hookah use among multi
      substance users may be contingent in part on individual factors including
      negative affectivity.

PMID- 27713681
TI  - Mass spectrometry-based approaches to targeted quantitative proteomics in
      cardiovascular disease.
AB  - Mass spectrometry-based proteomics methodology has become an important tool in
      elucidating some of the underlying mechanisms involved in cardiovascular disease.
      The present review provides details on selected important protein targets where
      highly selective and specific mass spectrometry-based approaches have led to
      important new findings and provided new mechanistic information. The role of six
      proteins involved in the etiology of cardiovascular disease (acetylated platelet
      cyclooxygenase-1, serum apolipoprotein A1, apolipoprotein C-III, serum C-reactive
      protein, serum high mobility group box-1 protein, insulin-like growth factor I)
      and their quantification has been discussed. There are an increasing number of
      examples where highly selective mass spectrometry-based quantification has
      provided new important data that could not be obtained with less labor intensive
      and cheaper immunoassay-based procedures. It is anticipated that these findings
      will lead to significant advances in a number of important issues related to the
      role of specific proteins in cardiovascular disease. The availability of a new
      generation of high-resolution high-sensitivity mass spectrometers will greatly
      facilitate these studies so that in the future it will be possible to analyze
      serum proteins of relevance to cardiovascular disease with levels of specificity
      and/or sensitivity that cannot be attained by immunoassay-based procedures.

PMID- 27713682
TI  - Enantiomeric Profiling of Chiral Pharmacologically Active Compounds in the
      Environment with the Usage of Chiral Liquid Chromatography ?Coupled with Tandem
      Mass Spectrometry.
AB  - The issue of drug chirality is attracting increasing attention among the
      scientific community. The phenomenon of chirality has been overlooked in
      environmental research (environmental occurrence, fate and toxicity) despite the
      great impact that chiral pharmacologically active compounds (cPACs) can provoke
      on ecosystems. The aim of this paper is to introduce the topic of chirality and
      its implications in environmental contamination. Special attention has been paid
      to the most recent advances in chiral analysis based on liquid chromatography
      coupled with mass spectrometry and the most popular protein based chiral
      stationary phases. Several groups of cPACs of environmental relevance, such as
      illicit drugs, human and veterinary medicines were discussed. The increase in the
      number of papers published in the area of chiral environmental analysis indicates
      that researchers are actively pursuing new opportunities to provide better
      understanding of environmental impacts resulting from the enantiomerism of cPACs.

PMID- 27713685
TI  - Spectral Transfer Learning Using Information Geometry for a User-Independent
      Brain-Computer Interface.
AB  - Recent advances in signal processing and machine learning techniques have enabled
      the application of Brain-Computer Interface (BCI) technologies to fields such as
      medicine, industry, and recreation; however, BCIs still suffer from the
      requirement of frequent calibration sessions due to the intra- and inter
      individual variability of brain-signals, which makes calibration suppression
      through transfer learning an area of increasing interest for the development of
      practical BCI systems. In this paper, we present an unsupervised transfer method
      (spectral transfer using information geometry, STIG), which ranks and combines
      unlabeled predictions from an ensemble of information geometry classifiers built
      on data from individual training subjects. The STIG method is validated in both
      off-line and real-time feedback analysis during a rapid serial visual
      presentation task (RSVP). For detection of single-trial, event-related potentials
      (ERPs), the proposed method can significantly outperform existing calibration
      free techniques as well as outperform traditional within-subject calibration
      techniques when limited data is available. This method demonstrates that
      unsupervised transfer learning for single-trial detection in ERP-based BCIs can
      be achieved without the requirement of costly training data, representing a step
      forward in the overall goal of achieving a practical user-independent BCI system.

PMID- 27713683
TI  - Specific Medical Conditions Are Associated with Unique Behavioral Profiles in
      Autism Spectrum Disorders.
AB  - Autism spectrum disorder (ASD) is a heterogeneous group of disorders which occurs
      with numerous medical conditions. In previous research, subtyping in ASD has been
      based mostly on cognitive ability and ASD symptom severity. The aim of the
      current study was to investigate whether specific medical conditions in ASD are
      associated with unique behavioral profiles. The medical conditions included in
      the study were macrocephaly, microcephaly, developmental regression, food
      selectivity, and sleep problems. The behavioral profile was composed of cognitive
      ability, adaptive skills, and autism severity, and was examined in each of the
      aforementioned medical conditions. The study population included 1224
      participants, 1043 males and 181 females (M:F ratio = 5.8:1) with a mean age of
      49.9 m (SD = 29.4) diagnosed with ASD using standardized tests. Groups with and
      without the specific medical conditions were compared on the behavioral measures.
      Developmental regression was present in 19% of the population and showed a more
      severe clinical presentation, with lower cognitive abilities, more severe ASD
      symptoms, and more impaired adaptive functioning. Microcephaly was observed in
      6.3% of the population and was characterized by a lower cognitive ability and
      more impaired adaptive functioning in comparison to the normative head
      circumference (HC) group. Severe food selectivity was found in 9.8% and severe
      sleep problems in 5.1% of the ASD population. The food selectivity and sleep
      problem subgroups, both showed more severe autism symptoms only as described by
      the parents, but not per the professional assessment, and more impaired adaptive
      skills. Macrocephaly was observed in 7.9% of the ASD population and did not
      differ from the normative HC group in any of the examined behavioral measures.
      Based on these findings, two unique medical-behavioral subtypes in ASD that
      affect inherited traits of cognition and/or autism severity were suggested. The
      microcephaly phenotype occurred with more impaired cognition and the
      developmental regression phenotype with widespread, more severe impairments in
      cognition and autism severity. In contrast, severe food selectivity and sleep
      problems represent only comorbidities to ASD that affect functioning. Defining
      specific subgroups in ASD with a unique biological signature and specific
      behavioral phenotypes may help future genetic and neuroscience research.

PMID- 27713684
TI  - Effects of Ceftriaxone on Glial Glutamate Transporters in Wistar Rats
      Administered Sequential Ethanol and Methamphetamine.
AB  - Methamphetamine (METH) is one of the psychostimulants that is co-abused with
      ethanol. Repeated exposure to high dose of METH has been shown to cause increases
      in extracellular glutamate concentration. We have recently reported that ethanol
      exposure can also increase the extracellular glutamate concentration and
      downregulate the expression of glutamate transporter subtype 1 (GLT-1). GLT-1 is
      a glial transporter that regulates the majority of extracellular glutamate. A
      Wistar rat model of METH and ethanol co-abuse was used to examine the expression
      of GLT-1 as well as other glutamate transporters such as cystine/glutamate
      exchanger (xCT) and glutamate aspartate transporter (GLAST). We also examined the
      body temperature in rats administered METH, ethanol or both drugs. We further
      investigated the effects of ceftriaxone (CEF), a beta-lactam antibiotic known to
      upregulate GLT-1, in this METH/ethanol co-abuse rat model. After 7 days of either
      ethanol (6 g/kg) or water oral gavage, Wistar rats received either saline or METH
      (10 mg/kg i.p. every 2 h * 4), followed by either saline or CEF (200 mg/kg)
      posttreatment. METH administered alone decreased GLT-1 expression in the nucleus
      accumbens (NAc) and prefrontal cortex (PFC) and increased body temperature, but
      did not reduce either xCT or GLAST expression in ethanol and water-pretreated
      rats. Interestingly, ethanol and METH were found to have an additive effect on
      the downregulation of GLT-1 expression in the NAc but not in the PFC. Moreover,
      ethanol alone caused GLT-1 downregulation in the NAc and elevated body
      temperature compared to control. Finally, CEF posttreatment significantly
      reversed METH-induced hyperthermia, restored GLT-1 expression, and increased xCT
      expression. These findings suggest the potential therapeutic role of CEF against
      METH- or ethanol/METH-induced hyperglutamatergic state and hyperthermia.

PMID- 27713686
TI  - Synthesis, Biodistribution and In vitro Evaluation of Brain Permeable High
      Affinity Type 2 Cannabinoid Receptor Agonists [11C]MA2 and [18F]MA3.
AB  - The type 2 cannabinoid receptor (CB2) is a member of the endocannabinoid system
      and is known for its important role in (neuro)inflammation. A PET-imaging agent
      that allows in vivo visualization of CB2 expression may thus allow quantification
      of neuroinflammation. In this paper, we report the synthesis, radiosynthesis,
      biodistribution and in vitro evaluation of a carbon-11 ([11C]MA2) and a fluorine
      18 ([18F]MA3) labeled analog of a highly potent N-arylamide oxadiazole CB2
      agonist (EC50 = 0.015 nM). MA2 and MA3 behaved as potent CB2 agonist (EC50: 3 nM
      and 0.1 nM, respectively) and their in vitro binding affinity for hCB2 was found
      to be 87 nM and 0.8 nM, respectively. Also MA3 (substituted with a fluoro ethyl
      group) was found to have higher binding affinity and EC50 values when compared to
      the originally reported trifluoromethyl analog 12. [11C]MA2 and [18F]MA3 were
      successfully synthesized with good radiochemical yield, high radiochemical purity
      and high specific activity. In mice, both tracers were efficiently cleared from
      blood and all major organs by the hepatobiliary pathway and importantly these
      compounds showed high brain uptake. In conclusion, [11C]MA2 and [18F]MA3 are
      shown to be high potent CB2 agonists with good brain uptake, these favorable
      characteristics makes them potential PET probes for in vivo imaging of brain CB2
      receptors. However, in view of its higher affinity and selectivity, further
      detailed evaluation of MA3 as a PET tracer for CB2 is warranted.

PMID- 27713687
TI  - Differential Effects of Toluene and Ethanol on Dopaminergic Neurons of the
      Ventral Tegmental Area.
AB  - Drugs of abuse increase the activity of dopaminergic neurons of the ventral
      tegmental area (VTA), and output from the VTA is critical for both natural and
      drug-induced reward and reinforcement. Ethanol and the abused inhalant toluene
      both enhance VTA neuronal firing, but the mechanisms of this effect is not fully
      known. In this study, we used extracellular recordings to compare the actions of
      toluene and ethanol on DA VTA neurons. Both ethanol and toluene increased the
      firing rate of DA neurons, although toluene was ~100 times more potent than
      ethanol. The mixed ion channel blocker quinine (100 MUM) blocked the increases in
      firing produced by ethanol and toluene, indicating some similarity in mechanisms
      of excitation. A mixture of antagonists of GABA and cholinergic receptors did not
      prevent toluene-induced or ethanol-induced excitation, and toluene-induced
      excitation was not altered by co-administration of ethanol, suggesting
      independent mechanisms of excitation for ethanol and toluene. Concurrent blockade
      of NMDA, AMPA, and metabotropic glutamate receptors enhanced the excitatory
      effect of toluene while having no significant effect on ethanol excitation.
      Nicotine increased firing of DA VTA neurons, and this was blocked by the
      nicotinic antagonist mecamylamine (1 MUM). Mecamylamine did not alter ethanol or
      toluene excitation of firing but the muscarinic antagonist atropine (5 MUM) or a
      combination of GABA antagonists (bicuculline and CGP35348, 10 MUM each) reduced
      toluene-induced excitation without affecting ethanol excitation. The Ih current
      blocker ZD7288 abolished the excitatory effect of toluene but unlike the block of
      ethanol excitation, the effect of ZD7288 was not reversed by the GIRK channel
      blocker barium, but was reversed by GABA antagonists. These results demonstrate
      that the excitatory effects of ethanol and toluene have some similarity, such as
      block by quinine and ZD7288, but also indicate that there are important
      differences between these two drugs in their modulation by glutamatergic,
      cholinergic, and GABAergic receptors. These findings provide important
      information regarding the actions of abused inhalants on central reward pathways,
      and suggest that regulation of the activation of central dopamine pathways by
      ethanol and toluene partially overlap.

PMID- 27713689
TI  - The Free Zinc Concentration in the Synaptic Cleft of Artificial Glycinergic
      Synapses Rises to At least 1 MUM.
AB  - Zn2+ is concentrated into presynaptic vesicles at many central synapses and is
      released into the synaptic cleft by nerve terminal stimulation. There is strong
      evidence that synaptically released Zn2+ modulates glutamatergic
      neurotransmission, although there is debate concerning the peak concentration it
      reaches in the synaptic cleft. Glycine receptors (GlyRs), which mediate
      inhibitory neurotransmission in the spinal cord and brainstem, are potentiated by
      low nanomolar Zn2+ and inhibited by micromolar Zn2+. Mutations that selectively
      ablate Zn2+ potentiation result in hyperekplexia phenotypes suggesting that Zn2+
      is a physiological regulator of glycinergic neurotransmission. There is, however,
      little evidence that Zn2+ is stored presynaptically at glycinergic terminals and
      an alternate possibility is that GlyRs are modulated by constitutively bound
      Zn2+. We sought to estimate the peak Zn2+ concentration in the glycinergic
      synaptic cleft as a means of evaluating whether it is likely to be synaptically
      released. We employed 'artificial' synapses because they permit the insertion of
      engineered alpha1beta GlyRs with defined Zn2+ sensitivities into synapses. By
      comparing the effect of Zn2+ chelation on glycinergic IPSCs with the effects of
      defined Zn2+ and glycine concentrations applied rapidly to the same recombinant
      GlyRs in outside-out patches, we inferred that synaptic Zn2+ rises to at least 1
      MUM following a single presynaptic stimulation. Moreover, using the fast, high
      affinity chelator, ZX1, we found no evidence for tonic Zn2+ bound constitutively
      to high affinity GlyR binding sites. We conclude that diffusible Zn2+ reaches 1
      MUM or higher and is therefore likely to be phasically released in artificial
      glycinergic synapses.

PMID- 27713688
TI  - Connexins and Pannexins: New Insights into Microglial Functions and Dysfunctions.
AB  - Under physiological conditions, microglia adopt a resting phenotype associated
      with the production of anti-inflammatory and neurotrophic factors. In response to
      a wide variety of insults, these cells shift to an activated phenotype that is
      necessary for the proper restoration of brain homeostasis. However, when the
      intensity of a threat is relatively high, microglial activation worsens the
      progression of damage rather than providing protection, with potentially
      significant consequences for neuronal survival. Coordinated interactions among
      microglia and other brain cells, including astrocytes and neurons, are critical
      for the development of timely and optimal inflammatory responses in the brain
      parenchyma. Tissue synchronization is in part mediated by connexins and
      pannexins, which are protein families that form different plasma membrane
      channels to communicate with neighboring cells. Gap junction channels (which are
      exclusively formed by connexins in vertebrates) connect the cytoplasm of
      contacting cells to coordinate electrical and metabolic coupling. Hemichannels
      (HCs) and pannexons (which are formed by connexins and pannexins, respectively)
      communicate the intra- and extracellular compartments and serve as diffusion
      pathways for the exchange of ions and small molecules. In this review article, we
      discuss the available evidence concerning the functional expression and
      regulation of connexin- and pannexin-based channels in microglia and their
      contributions to microglial function and dysfunction. Specifically, we focus on
      the possible implications of these channels in microglia-to-microglia, microglia
      to-astrocyte and neuron-to-microglia interactions in the inflamed brain.

PMID- 27713690
TI  - The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology
      Downstream of the Neurodevelopmental Disorder Factor Dysbindin.
AB  - AGAP1 is an Arf1 GTPase activating protein that interacts with the vesicle
      associated protein complexes adaptor protein 3 (AP-3) and Biogenesis of Lysosome
      Related Organelles Complex-1 (BLOC-1). Overexpression of AGAP1 in non-neuronal
      cells results in an accumulation of endosomal cargoes, which suggests a role in
      endosome-dependent traffic. In addition, AGAP1 is a candidate susceptibility gene
      for two neurodevelopmental disorders, autism spectrum disorder (ASD) and
      schizophrenia (SZ); yet its localization and function in neurons have not been
      described. Here, we describe that AGAP1 localizes to axons, dendrites, dendritic
      spines and synapses, colocalizing preferentially with markers of early and
      recycling endosomes. Functional studies reveal overexpression and down-regulation
      of AGAP1 affects both neuronal endosomal trafficking and dendritic spine
      morphology, supporting a role for AGAP1 in the recycling endosomal trafficking
      involved in their morphogenesis. Finally, we determined the sensitivity of AGAP1
      expression to mutations in the DTNBP1 gene, which is associated with
      neurodevelopmental disorder, and found that AGAP1 mRNA and protein levels are
      selectively reduced in the null allele of the mouse ortholog of DTNBP1. We
      postulate that endosomal trafficking contributes to the pathogenesis of
      neurodevelopmental disorders affecting dendritic spine morphology, and thus
      excitatory synapse structure and function.

PMID- 27713692
TI  - Determining Monkey Free Choice Long before the Choice Is Made: The Principal Role
      of Prefrontal Neurons Involved in Both Decision and Motor Processes.
AB  - When choices are made freely, they might emerge from pre-existing neural
      activity. However, whether neurons in the prefrontal cortex (PF) show this
      anticipatory effect and, if so, in which part of the process they are involved is
      still debated. To answer this question, we studied PF activity in monkeys while
      they performed a strategy task. In this task when the stimulus changed from the
      previous trial, the monkeys had to shift their response to one of two spatial
      goals, excluding the one that had been previously selected. Under this free
      choice condition, the prestimulus activity of the same neurons that are involved
      in decision and motor processes predicted future choices. These neurons developed
      the same goal preferences during the prestimulus presentation as they did later
      in the decision phase. In contrast, the same effect was not observed in motor
      only neurons and it was present but weaker in decision-only neurons. Overall, our
      results suggest that the PF neuronal activity predicts upcoming actions mainly
      through the decision-making network that integrate in time decision and motor
      task aspects.

PMID- 27713693
TI  - Patterns of Theta Activity in Limbic Anxiety Circuit Preceding Exploratory
      Behavior in Approach-Avoidance Conflict.
AB  - Theta oscillations within the hippocampus-amygdala-medial prefrontal cortex (HPC
      AMY-mPFC) circuit have been consistently implicated in the regulation of anxiety
      behaviors, including risk-assessment. To study if theta activity during risk
      assessment was correlated with exploratory behavior in an approach/avoidance
      paradigm we recorded simultaneous local field potentials from this circuit in
      rats exploring the elevated-plus maze (EPM). Opposing patterns of power
      variations in the ventral hippocampus (vHPC), basolateral amygdala (BLA), and
      prelimbic (PrL) mPFC, but not in the dorsal hippocampus (dHPC), during
      exploratory risk-assessment of the open arms preceded further exploration of the
      open arms or retreat back to the safer closed arms. The same patterns of theta
      power variations in the HPC-BLA-mPFC(PrL) circuit were also displayed by animals
      submitted to chronic unpredictable stress protocol known to induce an anxious
      state. Diverging patterns of vHPC-mPFC(PrL) theta coherence were also
      significantly correlated with forthcoming approach or avoidance behavior in the
      conflict situation in both controls and stressed animals; interestingly, vHPC
      BLA, and BLA-mPFC(PrL) theta coherence correlated with future behavior only in
      stressed animals, underlying the pivotal role of the amygdala on the stress
      response.

PMID- 27713694
TI  - Variation in the Oxytocin Receptor Gene Is Associated with Face Recognition and
      its Neural Correlates.
AB  - The ability to recognize faces is crucial for daily social interactions. Recent
      studies suggest that intranasal oxytocin administration improves social
      recognition in humans. Oxytocin signaling in the amygdala plays an essential role
      for social recognition in mice, and oxytocin administration has been shown to
      influence amygdala activity in humans. It is therefore possible that the effects
      of oxytocin on human social recognition depend on mechanisms that take place in
      the amygdala-a central region for memory processing also in humans. Variation in
      the gene encoding the oxytocin receptor (OXTR) has been associated with several
      aspects of social behavior. The present study examined the potential associations
      between nine OXTR polymorphisms, distributed across the gene, and the ability to
      recognize faces, as well as face-elicited amygdala activity measured by
      functional magnetic resonance imaging (fMRI) during incidental encoding of faces.
      The OXTR 3' polymorphism rs7632287, previously related to social bonding behavior
      and autism risk, was associated with participants' ability to recognize faces.
      Carriers of the GA genotype, associated with enhanced memory, displayed higher
      amygdala activity during face encoding compared to carriers of the GG genotype.
      In line with work in rodents, these findings suggest that, in humans, naturally
      occurring endogenous modulation of OXTR function affects social recognition
      through an amygdala-dependent mechanism. These findings contribute to the
      understanding of how oxytocin regulates human social behaviors.

PMID- 27713695
TI  - Are We Real When We Fake? Attunement to Object Weight in Natural and Pantomimed
      Grasping Movements.
AB  - Behavioral and neuropsychological studies suggest that real actions and
      pantomimed actions tap, at least in part, different neural systems. Inspired by
      studies showing weight-attunement in real grasps, here we asked whether (and to
      what extent) kinematics of pantomimed reach-to-grasp movement can reveal the
      weight of the pretended target. To address this question, we instructed
      participants (n = 15) either to grasp or pretend to grasp toward two differently
      weighted objects, i.e., a light object and heavy object. Using linear
      discriminant analysis, we then proceeded to classify the weight of the target -
      either real or pretended - on the basis of the recorded movement patterns.
      Classification analysis revealed that pantomimed reach-to-grasp movements
      retained information about object weight, although to a lesser extent than real
      grasp movements. These results are discussed in relation to the mechanisms
      underlying the control of real and pantomimed grasping movements.

PMID- 27713691
TI  - Characterizing and Modulating Brain Circuitry through Transcranial Magnetic
      Stimulation Combined with Electroencephalography.
AB  - The concurrent combination of transcranial magnetic stimulation (TMS) with
      electroencephalography (TMS-EEG) is a powerful technology for characterizing and
      modulating brain networks across developmental, behavioral, and disease states.
      Given the global initiatives in mapping the human brain, recognition of the
      utility of this technique is growing across neuroscience disciplines.
      Importantly, TMS-EEG offers translational biomarkers that can be applied in
      health and disease, across the lifespan, and in humans and animals, bridging the
      gap between animal models and human studies. However, to utilize the full
      potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is
      needed. In this article, we review the principles of TMS-EEG methodology, factors
      impacting TMS-EEG outcome measures, and the techniques for preventing and
      correcting artifacts in TMS-EEG data. To promote the standardization of this
      technique, we provide comprehensive guides for designing TMS-EEG studies and
      conducting TMS-EEG experiments. We conclude by reviewing the application of TMS
      EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of
      this emerging technology in brain research.

PMID- 27713696
TI  - Development of Effective Connectivity during Own- and Other-Race Face Processing:
      A Granger Causality Analysis.
AB  - Numerous developmental studies have suggested that other-race effect (ORE) in
      face recognition emerges as early as in infancy and develops steadily throughout
      childhood. However, there is very limited research on the neural mechanisms
      underlying this developmental ORE. The present study used Granger causality
      analysis (GCA) to examine the development of children's cortical networks in
      processing own- and other-race faces. Children were between 3 and 13 years. An
      old-new paradigm was used to assess their own- and other-race face recognition
      with ETG-4000 (Hitachi Medical Co., Japan) acquiring functional near infrared
      spectroscopy (fNIRS) data. After preprocessing, for each participant and under
      each face condition, we obtained the causal map by calculating the weights of
      causal relations between the time courses of [oxy-Hb] of each pair of channels
      using GCA. To investigate further the differential causal connectivity for own
      race faces and other-race faces at the group level, a repeated measure analysis
      of variance (ANOVA) was performed on the GCA weights for each pair of channels
      with the face race task (own-race face vs. other-race face) as the within-subject
      variable and the age as a between-subject factor (continuous variable). We found
      an age-related increase in functional connectivity, paralleling a similar age
      related improvement in behavioral face processing ability. More importantly, we
      found that the significant differences in neural functional connectivity between
      the recognition of own-race faces and that of other-race faces were modulated by
      age. Thus, like the behavioral ORE, the neural ORE emerges early and undergoes a
      protracted developmental course.

PMID- 27713698
TI  - Stress Assessment by Prefrontal Relative Gamma.
AB  - Stress assessment has been under study in the last years. Both biochemical and
      physiological markers have been used to measure stress level. In neuroscience,
      several studies have related modification of stress level to brain activity
      changes in limbic system and frontal regions, by using non-invasive techniques
      such as functional magnetic resonance imaging (fMRI) and electroencephalography
      (EEG). In particular, previous studies suggested that the exhibition or
      inhibition of certain brain rhythms in frontal cortical areas indicates stress.
      However, there is no established marker to measure stress level by EEG. In this
      work, we aimed to prove the usefulness of the prefrontal relative gamma power
      (RG) for stress assessment. We conducted a study based on stress and relaxation
      periods. Six healthy subjects performed the Montreal Imaging Stress Task (MIST)
      followed by a stay within a relaxation room while EEG and electrocardiographic
      signals were recorded. Our results showed that the prefrontal RG correlated with
      the expected stress level and with the heart rate (HR; 0.8). In addition, the
      difference in prefrontal RG between time periods of different stress level was
      statistically significant (p < 0.01). Moreover, the RG was more discriminative
      between stress levels than alpha asymmetry, theta, alpha, beta, and gamma power
      in prefrontal cortex. We propose the prefrontal RG as a marker for stress
      assessment. Compared with other established markers such as the HR or the
      cortisol, it has higher temporal resolution. Additionally, it needs few
      electrodes located at non-hairy head positions, thus facilitating the use of non
      invasive dry wearable real-time devices for ubiquitous assessment of stress.

PMID- 27713697
TI  - Does the Cerebral Cortex Exploit High-Dimensional, Non-linear Dynamics for
      Information Processing?
AB  - The discovery of stimulus induced synchronization in the visual cortex suggested
      the possibility that the relations among low-level stimulus features are encoded
      by the temporal relationship between neuronal discharges. In this framework,
      temporal coherence is considered a signature of perceptual grouping. This insight
      triggered a large number of experimental studies which sought to investigate the
      relationship between temporal coordination and cognitive functions. While some
      core predictions derived from the initial hypothesis were confirmed, these
      studies, also revealed a rich dynamical landscape beyond simple coherence whose
      role in signal processing is still poorly understood. In this paper, a framework
      is presented which establishes links between the various manifestations of
      cortical dynamics by assigning specific coding functions to low-dimensional
      dynamic features such as synchronized oscillations and phase shifts on the one
      hand and high-dimensional non-linear, non-stationary dynamics on the other. The
      data serving as basis for this synthetic approach have been obtained with chronic
      multisite recordings from the visual cortex of anesthetized cats and from monkeys
      trained to solve cognitive tasks. It is proposed that the low-dimensional
      dynamics characterized by synchronized oscillations and large-scale correlations
      are substates that represent the results of computations performed in the high
      dimensional state-space provided by recurrently coupled networks.

PMID- 27713699
TI  - Plant Alkaloids as Antiplatelet Agent: Drugs of the Future in the Light of Recent
      Developments.
AB  - An alkaloid is a class of naturally occurring organic nitrogen-containing
      compounds that are frequently found in the plant kingdom. Many alkaloids are
      valuable medicinal agents that can be utilized to treat various diseases
      including malaria, diabetics, cancer, cardiac dysfunction etc. Similarly,
      platelet aggregation beyond the purpose of homeostasis is the underlying cause of
      blood clotting related diseases. This review presents a thorough understanding of
      alkaloids as antiplatelet agents with a possible mechanism of action based on the
      literature of the last decade. In addition, this review will address the
      antiplatelet activity of alkaloids and their medicinal usage as potent
      antiplatelet agents with a description of structural relationship activity and
      possible lead compounds for future drug discovery.

PMID- 27713701
TI  - Improvements in Cycling Time Trial Performance Are Not Sustained Following the
      Acute Provision of Challenging and Deceptive Feedback.
AB  - The provision of performance-related feedback during exercise is acknowledged as
      an influential external cue used to inform pacing decisions. The provision of
      this feedback in a challenging or deceptive context allows research to explore
      how feedback can be used to improve performance and influence perceptual
      responses. However, the effects of deception on both acute and residual responses
      have yet to be explored, despite potential application for performance
      enhancement. Therefore, this study investigated the effects of challenging and
      deceptive feedback on perceptual responses and performance in self-paced cycling
      time trials (TT) and explored whether changes in performance are sustained in a
      subsequent TT following the disclosure of the deception. Seventeen trained male
      cyclists were assigned to either an accurate or deceptive feedback group and
      performed four 16.1 km cycling TTs; (1 and 2) ride-alone baseline TTs where a
      fastest baseline (FBL) performance was identified, (3) a TT against a virtual
      avatar representing 102% of their FBL performance (PACER), and (4) a subsequent
      ride-alone TT (SUB). The deception group, however, were initially informed that
      the avatar accurately represented their FBL, but prior to SUB were correctly
      informed of the nature of the avatar. Affect, self-efficacy and RPE were measured
      every quartile. Both groups performed PACER faster than FBL and SUB (p < 0.05)
      and experienced lower affect (p = 0.016), lower self-efficacy (p = 0.011), and
      higher RPE (p < 0.001) in PACER than FBL. No significant differences were found
      between FBL and SUB for any variable. The presence of the pacer rather than the
      manipulation of performance beliefs acutely facilitates TT performance and
      perceptual responses. Revealing that athletes' performance beliefs were falsely
      negative due to deceptive feedback provision has no effect on subsequent
      perceptions or performance. A single experiential exposure may not be sufficient
      to produce meaningful changes in the performance beliefs of trained individuals
      beyond the acute setting.

PMID- 27713702
TI  - Population Dynamics and Flight Phenology Model of Codling Moth Differ between
      Commercial and Abandoned Apple Orchard Ecosystems.
AB  - Apple orchard management practices may affect development and phenology of
      arthropod pests, such as the codling moth (CM), Cydia pomonella (L.)
      (Lepidoptera: Tortricidae), which is a serious internal fruit-feeding pest of
      apples worldwide. Estimating population dynamics and accurately predicting the
      timing of CM development and phenology events (for instance, adult flight, and
      egg-hatch) allows growers to understand and control local populations of CM.
      Studies were conducted to compare the CM flight phenology in commercial and
      abandoned apple orchard ecosystems using a logistic function model based on
      degree-days accumulation. The flight models for these orchards were derived from
      the cumulative percent moth capture using two types of commercially available CM
      lure baited traps. Models from both types of orchards were also compared to
      another model known as PETE (prediction extension timing estimator) that was
      developed in 1970s to predict life cycle events for many fruit pests including CM
      across different fruit growing regions of the United States. We found that the
      flight phenology of CM was significantly different in commercial and abandoned
      orchards. CM male flight patterns for first and second generations as predicted
      by the constrained and unconstrained PCM (Pennsylvania Codling Moth) models in
      commercial and abandoned orchards were different than the flight patterns
      predicted by the currently used CM model (i.e., PETE model). In commercial
      orchards, during the first and second generations, the PCM unconstrained model
      predicted delays in moth emergence compared to current model. In addition, the
      flight patterns of females were different between commercial and abandoned
      orchards. Such differences in CM flight phenology between commercial and
      abandoned orchard ecosystems suggest potential impact of orchard environment and
      crop management practices on CM biology.

PMID- 27713700
TI  - Drug Discovery via Human-Derived Stem Cell Organoids.
AB  - Patient-derived cell lines and animal models have proven invaluable for the
      understanding of human intestinal diseases and for drug development although both
      inherently comprise disadvantages and caveats. Many genetically determined
      intestinal diseases occur in specific tissue microenvironments that are not
      adequately modeled by monolayer cell culture. Likewise, animal models
      incompletely recapitulate the complex pathologies of intestinal diseases of
      humans and fall short in predicting the effects of candidate drugs. Patient
      derived stem cell organoids are new and effective models for the development of
      novel targeted therapies. With the use of intestinal organoids from patients with
      inherited diseases, the potency and toxicity of drug candidates can be evaluated
      better. Moreover, owing to the novel clustered regularly interspaced short
      palindromic repeats/CRISPR-associated protein-9 genome-editing technologies,
      researchers can use organoids to precisely modulate human genetic status and
      identify pathogenesis-related genes of intestinal diseases. Therefore, here we
      discuss how patient-derived organoids should be grown and how advanced genome
      editing tools may be applied to research on modeling of cancer and infectious
      diseases. We also highlight practical applications of organoids ranging from
      basic studies to drug screening and precision medicine.

PMID- 27713703
TI  - Gene Expression in Response to Exercise in Patients with Chronic Fatigue
      Syndrome: A Pilot Study.
AB  - Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown
      pathogenesis, characterized by fatigue, which is exacerbated after minimal
      exercise. We examined the effect of a single bout of aerobic exercise on
      leucocyte mRNA expression of genes putatively linked to exaggerated afferent
      signaling as an under-pinning of the fatigue state. A carefully-characterized
      sample of patients with CFS (N = 10) and healthy matched control participants (N
      = 12) were included. Participant ratings of fatigue and other symptoms, as well
      as blood samples, were obtained at baseline, and five other time-points up to 72
      h after 25 min of moderate-intensity cycling exercise. Leucocyte mRNA of 19
      metabolite-sensing, adrenergic, immune, and neurotransmission genes was examined
      using quantitative polymerase chain reaction. Patients with CFS reported
      substantial fatigue, functional impairment, and poor sleep at baseline (all p <
      0.02), and exercise immediately induced worsened patients' fatigue (effect size,
      ES = 1.17). There were no significant changes in gene expression after exercise
      and patients did not differ from control participants at any time point. Higher
      levels of expression of ficolin (FCN1) and a purinergic receptor (P2RX4) in
      patients with CFS were found when all time points were combined. Patients with
      CFS did not show significant exercise-induced changes in leucocyte mRNA of 19
      metabolite-sensing, adrenergic, immune and neurotransmission genes despite a
      prominent exacerbation of fatigue.

PMID- 27713704
TI  - Editorial: Impact of Lipid Peroxidation on the Physiology and Pathophysiology of
      Cell Membranes.

PMID- 27713706
TI  - Detecting Superior Face Recognition Skills in a Large Sample of Young British
      Adults.
AB  - The Cambridge Face Memory Test Long Form (CFMT+) and Cambridge Face Perception
      Test (CFPT) are typically used to assess the face processing ability of
      individuals who believe they have superior face recognition skills. Previous
      large-scale studies have presented norms for the CFPT but not the CFMT+. However,
      previous research has also highlighted the necessity for establishing country
      specific norms for these tests, indicating that norming data is required for both
      tests using young British adults. The current study addressed this issue in 254
      British participants. In addition to providing the first norm for performance on
      the CFMT+ in any large sample, we also report the first UK specific cut-off for
      superior face recognition on the CFPT. Further analyses identified a small
      advantage for females on both tests, and only small associations between
      objective face recognition skills and self-report measures. A secondary aim of
      the study was to examine the relationship between trait or social anxiety and
      face processing ability, and no associations were noted. The implications of
      these findings for the classification of super-recognizers are discussed.

PMID- 27713705
TI  - Pacemaking Property of RVLM Presympathetic Neurons.
AB  - Despite several studies describing the electrophysiological properties of RVLM
      presympathetic neurons, there is no consensus in the literature about their
      pacemaking property, mainly due to different experimental approaches used for
      recordings of neuronal intrinsic properties. In this review we are presenting a
      historical retrospective about the pioneering studies and their controversies on
      the intrinsic electrophysiological property of auto-depolarization of these cells
      in conjunction with recent studies from our laboratory documenting that RVLM
      presympathetic neurons present pacemaking capacity. We also discuss whether
      increased sympathetic activity observed in animal models of neurogenic
      hypertension (CIH and SHR) are dependent on changes in the intrinsic
      electrophysiological properties of these cells or due to changes in modulatory
      inputs from neurons of the respiratory network. We also highlight the key role of
      INaP as the major current contributing to the pacemaking property of RVLM
      presympathetic neurons.

PMID- 27713707
TI  - How to Measure the Intervention Process? An Assessment of Qualitative and
      Quantitative Approaches to Data Collection in the Process Evaluation of
      Organizational Interventions.
AB  - Organizational interventions aiming at improving employee health and wellbeing
      have proven to be challenging to evaluate. To analyze intervention processes two
      methodological approaches have widely been used: quantitative (often
      questionnaire data), or qualitative (often interviews). Both methods are
      established tools, but their distinct epistemological properties enable them to
      illuminate different aspects of organizational interventions. In this paper, we
      use the quantitative and qualitative process data from an organizational
      intervention conducted in a national postal service, where the Intervention
      Process Measure questionnaire (N = 285) as well as an extensive interview study
      (N = 50) were used. We analyze what type of knowledge about intervention
      processes these two methodologies provide and discuss strengths and weaknesses as
      well as potentials for mixed methods evaluation methodologies.

PMID- 27713708
TI  - Implications of "Too Good to Be True" for Replication, Theoretical Claims, and
      Experimental Design: An Example Using Prominent Studies of Racial Bias.
AB  - In response to concerns about the validity of empirical findings in psychology,
      some scientists use replication studies as a way to validate good science and to
      identify poor science. Such efforts are resource intensive and are sometimes
      controversial (with accusations of researcher incompetence) when a replication
      fails to show a previous result. An alternative approach is to examine the
      statistical properties of the reported literature to identify some cases of poor
      science. This review discusses some details of this process for prominent
      findings about racial bias, where a set of studies seems "too good to be true."
      This kind of analysis is based on the original studies, so it avoids criticism
      from the original authors about the validity of replication studies. The analysis
      is also much easier to perform than a new empirical study. A variation of the
      analysis can also be used to explore whether it makes sense to run a replication
      study. As demonstrated here, there are situations where the existing data suggest
      that a direct replication of a set of studies is not worth the effort. Such a
      conclusion should motivate scientists to generate alternative experimental
      designs that better test theoretical ideas.

PMID- 27713709
TI  - Effect of a Mindfulness Training Program on the Impulsivity and Aggression Levels
      of Adolescents with Behavioral Problems in the Classroom.
AB  - Objective: The aim of the present study was to analyze the effects of a
      mindfulness training psycho-educative program on impulsivity and aggression
      levels in a sample of high school students. Methods: A randomized controlled
      trial with pre-test-post-test measurements was applied to an experimental group
      and a control group (waiting list). The Barratt Impulsivity Scale (BIS-11) Patton
      et al. (1995) and the Aggression Questionnaire (Buss and Perry, 1992) were used.
      Results: Statistical analyses showed a significant decrease in the levels of
      impulsivity and aggressiveness in the experimental group compared with the
      control group. These results have important implications for improving the level
      of academic engagement and self-efficacy of students and for reducing school
      failure. Conclusion: This is one of the first studies showing the effectiveness
      of mindfulness training at reducing impulsive and aggressive behaviors in the
      classroom. The efficacy of mindfulness-based programs is emphasized.

PMID- 27713710
TI  - Cognitive Reflection, Decision Biases, and Response Times.
AB  - We present novel evidence on response times and personality traits in standard
      questions from the decision-making literature where responses are relatively slow
      (medians around half a minute or above). To this end, we measured response times
      in a number of incentivized, framed items (decisions from description) including
      the Cognitive Reflection Test, two additional questions following the same logic,
      and a number of classic questions used to study decision biases in probability
      judgments (base-rate neglect, the conjunction fallacy, and the ratio bias). All
      questions create a conflict between an intuitive process and more deliberative
      thinking. For each item, we then created a non-conflict version by either making
      the intuitive impulse correct (resulting in an alignment question), shutting it
      down (creating a neutral question), or making it dominant (creating a heuristic
      question). For CRT questions, the differences in response times are as predicted
      by dual-process theories, with alignment and heuristic variants leading to faster
      responses and neutral questions to slower responses than the original, conflict
      questions. For decision biases (where responses are slower), evidence is mixed.
      To explore the possible influence of personality factors on both choices and
      response times, we used standard personality scales including the Rational
      Experiential Inventory and the Big Five, and used them as controls in regression
      analysis.

PMID- 27713711
TI  - Work Characteristics and Occupational Well-Being: The Role of Age.
AB  - Based on a lifespan perspective on work design, person-environment interaction
      and fit theories, models of successful aging at work, and role theory, we review
      research on the role of worker age in relationships between work characteristics
      and occupational well-being. We first focus on interaction effects of work
      characteristics and age on occupational well-being. Research has found that age
      can moderate associations between work characteristics and occupational well
      being indicators, and that work characteristics can moderate associations between
      age and occupational well-being indicators. Next, we describe research showing
      that work characteristics can mediate associations between age and occupational
      well-being indicators. The relationships of age with specific work
      characteristics and occupational well-being indicators can be linear or non
      linear. We conclude our literature review by discussing implications for future
      research.

PMID- 27713714
TI  - Editorial: When (and How) Is Theory of Mind Useful? Evidence from Life-Span
      Research.

PMID- 27713713
TI  - Isochronous Sequential Presentation Helps Children Orient Their Attention in
      Time.
AB  - Knowing when an event is likely to occur allows attentional resources to be
      oriented toward that moment in time, enhancing processing of the event. We
      previously found that children (mean age 11 years) are unable to use endogenous
      temporal cues to orient attention in time, despite being able to use endogenous
      spatial cues (arrows) to orient attention in space. Arrow cues, however, may have
      proved beneficial by engaging exogenous (automatic), as well as endogenous
      (voluntary), orienting mechanisms. We therefore conducted two studies in which
      the exogenous properties of visual temporal cues were increased, to examine
      whether this helped children orient their attention in time. In the first study,
      the location of an imperative target was predicted by the direction of a left or
      right spatial arrow cue while its onset was predicted by the relative duration of
      a short or long temporal cue. To minimize the influence of rhythmic entrainment
      in the temporal condition, the foreperiod (500 ms/1100 ms) was deliberately
      chosen so as not to precisely match the duration of the temporal cue (100 ms/400
      ms). Targets appeared either at cued locations/onset times (valid trials) or at
      unexpected locations/onset times (invalid trials). Adults' response times were
      significantly slower for invalid versus valid trials, in both spatial and
      temporal domains. Despite being slowed by invalid spatial cues, children (mean
      age 10.7 years) were unperturbed by invalid temporal cues, suggesting that these
      duration-based temporal cues did not help them orient attention in time. In the
      second study, we enhanced the exogenous properties of temporal cues further, by
      presenting multiple temporal cues in an isochronous (rhythmic) sequence. Again,
      to minimize automatic entrainment, target onset did not match the isochronous
      interval. Children (mean age 11.4 years), as well as adults, were now
      significantly slowed by invalid cues in both the temporal and spatial dimension.
      The sequential, as opposed to single, presentation of temporal cues therefore
      helped children to orient their attention in time. We suggest that the exogenous
      properties of sequential presentation provide a temporal scaffold that supports
      the additional attentional and mnemonic requirements of temporal, as compared to
      spatial, processing.

PMID- 27713712
TI  - Vowels and Consonants in the Brain: Evidence from Magnetoencephalographic Studies
      on the N1m in Normal-Hearing Listeners.
AB  - Speech sound perception is one of the most fascinating tasks performed by the
      human brain. It involves a mapping from continuous acoustic waveforms onto the
      discrete phonological units computed to store words in the mental lexicon. In
      this article, we review the magnetoencephalographic studies that have explored
      the timing and morphology of the N1m component to investigate how vowels and
      consonants are computed and represented within the auditory cortex. The neurons
      that are involved in the N1m act to construct a sensory memory of the stimulus
      due to spatially and temporally distributed activation patterns within the
      auditory cortex. Indeed, localization of auditory fields maps in animals and
      humans suggested two levels of sound coding, a tonotopy dimension for spectral
      properties and a tonochrony dimension for temporal properties of sounds. When the
      stimulus is a complex speech sound, tonotopy and tonochrony data may give
      important information to assess whether the speech sound parsing and decoding are
      generated by pure bottom-up reflection of acoustic differences or whether they
      are additionally affected by top-down processes related to phonological
      categories. Hints supporting pure bottom-up processing coexist with hints
      supporting top-down abstract phoneme representation. Actually, N1m data
      (amplitude, latency, source generators, and hemispheric distribution) are limited
      and do not help to disentangle the issue. The nature of these limitations is
      discussed. Moreover, neurophysiological studies on animals and neuroimaging
      studies on humans have been taken into consideration. We compare also the N1m
      findings with the investigation of the magnetic mismatch negativity (MMNm)
      component and with the analogous electrical components, the N1 and the MMN. We
      conclude that N1 seems more sensitive to capture lateralization and hierarchical
      processes than N1m, although the data are very preliminary. Finally, we suggest
      that MEG data should be integrated with EEG data in the light of the neural
      oscillations framework and we propose some concerns that should be addressed by
      future investigations if we want to closely line up language research with issues
      at the core of the functional brain mechanisms.

PMID- 27713715
TI  - Editorial: Neuro-Education and Neuro-Rehabilitation.

PMID- 27713716
TI  - Inattention, Working Memory, and Goal Neglect in a Community Sample.
AB  - Executive function deficits have been linked to attention deficit hyperactivity
      disorder (ADHD), but it has been theorized that the symptom inattention is
      specifically related to problems with complex verbal working memory (WM). Using
      the Conners Adult ADHD rating scale, adults aged 18-35 were assessed for ADHD
      symptoms, and completed tasks designed to tap verbal and spatial aspects of WM
      (Experiment 1). Results showed that high inattention predicted poor performance
      on both simple and complex verbal WM measures. Results relating to spatial WM
      were inconclusive. In a follow up experiment based on the theory that those with
      inattention have problems receiving verbal instructions, a measure of goal
      neglect assessing integration of information into a task model in WM was employed
      (Experiment 2). Results showed that high inattention uniquely predicted
      performance on this task, representing the first reported association between
      inattention and the phenomenon of goal neglect. The results from both experiments
      lend support to the WM theory of inattention.

PMID- 27713717
TI  - Just Google It: Young Children's Preferences for Touchscreens versus Books in
      Hypothetical Learning Tasks.
AB  - Children today regularly interact with touchscreen devices (Rideout, 2013) and
      thousands of "educational" mobile applications are marketed to them (Shuler,
      2012). Understanding children's own ideas about optimal learning has important
      implications for education, which is being transformed by electronic mobile
      devices, yet we know little about how children think about such devices,
      including what children think touchscreens are useful for. Based on a prior
      result that children prefer a book over a touchscreen for learning about dogs,
      the present study explored how children view touchscreens versus books for
      learning an array of different types of information. Seventy children ages 3-6
      were presented with six different topics (cooking, today's weather, trees,
      vacuums, Virginia, and yesterday's football game) and chose whether a book or a
      touchscreen device would be best to use to learn about each topic. Some of this
      information was time-sensitive, like the current weather; we predicted that
      children would prefer a touchscreen for time-sensitive information. In addition,
      each child's parent was surveyed about the child's use of books and touchscreens
      for educational purposes, both at home and in school. Results indicated that
      younger children had no preference between books and touchscreen devices across
      learning tasks. However, 6-year-olds were significantly more likely to choose the
      touchscreen for several topics. Surprisingly, 6-year-olds chose a touchscreen
      device to learn about time-sensitive weather conditions, but not yesterday's
      football. Children's choices were not associated with their use of books and
      touchscreens at home and school.

PMID- 27713718
TI  - Processing Metrical Information in Silent Reading: An ERP Study.
AB  - Listeners are sensitive to the metric structure of words, i.e., an alternating
      pattern of stressed and unstressed syllables, in auditory speech processing:
      Event-related potentials recorded as participants listen to a sequence of words
      with a consistent metrical pattern, e.g., a series of trochaic words, suggest
      that participants register words metrically incongruent with the preceding
      sequence. Here we examine whether the processing of individual words in silent
      reading is similarly impacted by rhythmic properties of the surrounding context.
      We recorded participants' EEG as they read lists of either three trochaic or
      iambic disyllabic words followed by a target word that was either congruent or
      incongruent with the preceding metric pattern. Event-Related Potentials (ERPs) to
      targets were modulated by an interaction between metrical structure (iambic vs.
      trochaic) and congruence: for iambs, more positive ERPs were observed in the
      incongruent than congruent condition 250-400 ms and 400-600 ms post-stimulus,
      whereas no reliable impact of congruence was found for trochees. We suggest that
      when iambs are in an incongruent context, i.e., preceded by trochees, the context
      contains the metrical structure that is more typical in participants' native
      language which facilitates processing relative to when they are presented in a
      congruent context, containing the less typical, i.e., iambic, metrical structure.
      The results provide evidence that comprehenders are sensitive to the prosodic
      properties of the context even in silent reading, such that this sensitivity
      impacts lexico-semantic processing of individual words.

PMID- 27713719
TI  - Lay Explanatory Models of Depression and Preferred Coping Strategies among Somali
      Refugees in Norway. A Mixed-Method Study.
AB  - Objective: Refugees are at high risk of experiencing mental health problems due
      to trauma in their pasts and to acculturation stress as they settle in a new
      country. To develop efficient health services that meet the needs of refugees
      from different regions, an understanding is required of how they make sense of
      and prefer to cope with mental health problems. This study aims to investigate
      lay explanatory models of depression and preferred coping strategies among Somali
      refugees in Norway. Methods: The study used a mixed-method design with a vignette
      describing a moderately depressed person based on ICD-10 criteria. Firstly, a
      survey study was performed among Somali refugees (n = 101). Respondents were
      asked to give advice to the vignette character and complete the Cross-Cultural
      Depression Coping Inventory and the General Help-Seeking Questionnaire. Secondly,
      focus group interviews (n = 10) were conducted separately with males and females
      to examine the relationship between the explanatory models of depression and the
      preferred coping strategies. Results: The participants showed a strong preference
      for coping with depression by religious practices and reliance on family,
      friends, and their ethnic/religious community, rather than by seeking
      professional treatment from public health services (e.g., medical doctors,
      psychologists). Depressive symptoms were conceptualized as a problem related to
      cognition (thinking too much) and emotion (sadness), but not to biological
      mechanisms, and they were thought to result from spiritual possession, stress as
      a result of social isolation, and/or past trauma. Independently of time in exile,
      the participants showed a strong identification with their ethnic origin and
      associated values. Because participants emphasized the need to obey and follow
      the views of elders, fathers, and spiritual leaders, these authorities seemed to
      be "gatekeepers" for access to mental health services. Conclusion: The results
      highlight that mental health programs for Somali refugees should actively involve
      the ethnic community, including spiritual leaders, in order to reach patients in
      need and to foster treatment compliance.

PMID- 27713720
TI  - Romantic Love vs. Drug Addiction May Inspire a New Treatment for Addiction.
AB  - Drug addiction is a complex neurological dysfunction induced by recurring drug
      intoxication. Strategies to prevent and treat drug addiction constitute a topic
      of research interest. Early-stage romantic love is characterized by some
      characteristics of addiction, which gradually disappear as the love relationship
      progresses. Therefore, comparison of the concordance and discordance between
      romantic love and drug addiction may elucidate potential treatments for
      addiction. This focused review uses the evidences from our recent studies to
      compare the neural alterations between romantic love and drug addiction, moreover
      we also compare the behavioral and neurochemical alterations between romantic
      love and drug addiction. From the behavioral comparisons we find that there are
      many similarities between the early stage of romantic love and drug addiction,
      and this stage romantic love is considered as a behavioral addiction, while
      significant differences exist between the later stage of romantic love and drug
      addiction, and this stage of romantic love eventually developed into a prosocial
      behavior. The neuroimaging comparisons suggest that romantic love and drug
      addiction both display the functional enhancement in reward and emotion
      regulation network. Except the similar neural changes, romantic love display
      special function enhancement in social cognition network, while drug addiction
      display special dysfunction in cognitive control network. The neurochemical
      comparisons show that there are many similarities in the dopamine (DA) system,
      while significant differences in oxytocin (OT) system for romantic love and drug
      addiction. These findings indicate that the functional alterations in reward and
      emotion regulation network and the DA system may be the neurophysiological basis
      of romantic love as a behavioral addiction, and the functional alterations in
      social cognition network and the OT system may be the neurophysiological basis of
      romantic love as a prosocial behavior. It seems that the OT system is a critical
      factor for the development of addiction. So we then discuss strategies to treat
      drug addiction with OT, and suggest that future research should further
      investigate OT system interventions aiming to improve cognitive control and/or
      social cognition functions, in order to develop strategies designed to more
      effectively treat drug addiction.

PMID- 27713721
TI  - Modulating the Activity of Ventromedial Prefrontal Cortex by Anodal tDCS Enhances
      the Trustee's Repayment through Altruism.
AB  - Trust and trustworthiness are essential to an efficient economy and play crucial
      roles in social life. Previous evidence from behavioral experiments has revealed
      that the trustworthiness of individuals is closely related with their altruistic
      preference. It has been demonstrated that the ventromedial prefrontal cortex
      (vmPFC) is associated with decisions involving trustworthiness. Moreover, vmPFC
      lesion patients showed less trustworthiness and altruism than control subjects,
      indicating the indispensable role of this specific brain area in human social
      interactions. However, the causal relationship between this neural area and
      trustworthiness, as well as altruism, has not been fully revealed. The potential
      neural basis behind the behavior of trustees' repayment has also seldom been
      discussed. In the present study, we aimed to provide evidence of a direct link
      between the neural and behavioral results through the application of transcranial
      direct current stimulation (tDCS) over the vmPFC of our participants. We found
      that activating the vmPFC could promote both the trustworthiness and altruism of
      our participants. We also show that enhancing the excitability of the vmPFC using
      tDCS increased the trustworthiness of the participants, and this promoting effect
      might be attributable to the enhancement of individuals' altruistic preference.
      In addition, we revealed that the enhancing effect in trustworthiness and
      altruism might be specific to the activation of the vmPFC by applying tDCS over
      another brain region within the prefrontal cortex as a control site. Crucially,
      our findings provide direct evidence supporting the critical role of the vmPFC in
      cooperative behaviors in economic interactions, especially the trustees'
      repayment in the trust game and the dictators' altruistic transfer in the
      dictator game.

PMID- 27713722
TI  - Episodic Short-Term Recognition Requires Encoding into Visual Working Memory:
      Evidence from Probe Recognition after Letter Report.
AB  - Human vision is organized in discrete processing episodes (e.g., eye fixations or
      task-steps). Object information must be transmitted across episodes to enable
      episodic short-term recognition: recognizing whether a current object has been
      seen in a previous episode. We ask whether episodic short-term recognition
      presupposes that objects have been encoded into capacity-limited visual working
      memory (VWM), which retains visual information for report. Alternatively, it
      could rely on the activation of visual features or categories that occurs before
      encoding into VWM. We assessed the dependence of episodic short-term recognition
      on VWM by a new paradigm combining letter report and probe recognition.
      Participants viewed displays of 10 letters and reported as many as possible after
      a retention interval (whole report). Next, participants viewed a probe letter and
      indicated whether it had been one of the 10 letters (probe recognition). In
      Experiment 1, probe recognition was more accurate for letters that had been
      encoded into VWM (reported letters) compared with non-encoded letters (non
      reported letters). Interestingly, those letters that participants reported in
      their whole report had been near to one another within the letter displays. This
      suggests that the encoding into VWM proceeded in a spatially clustered manner. In
      Experiment 2, participants reported only one of 10 letters (partial report) and
      probes either referred to this letter, to letters that had been near to it, or
      far from it. Probe recognition was more accurate for near than for far letters,
      although none of these letters had to be reported. These findings indicate that
      episodic short-term recognition is constrained to a small number of
      simultaneously presented objects that have been encoded into VWM.

PMID- 27713723
TI  - A Tutorial on Hunting Statistical Significance by Chasing N.
AB  - There is increasing concern about the replicability of studies in psychology and
      cognitive neuroscience. Hidden data dredging (also called p-hacking) is a major
      contributor to this crisis because it substantially increases Type I error
      resulting in a much larger proportion of false positive findings than the usually
      expected 5%. In order to build better intuition to avoid, detect and criticize
      some typical problems, here I systematically illustrate the large impact of some
      easy to implement and so, perhaps frequent data dredging techniques on boosting
      false positive findings. I illustrate several forms of two special cases of data
      dredging. First, researchers may violate the data collection stopping rules of
      null hypothesis significance testing by repeatedly checking for statistical
      significance with various numbers of participants. Second, researchers may group
      participants post hoc along potential but unplanned independent grouping
      variables. The first approach 'hacks' the number of participants in studies, the
      second approach 'hacks' the number of variables in the analysis. I demonstrate
      the high amount of false positive findings generated by these techniques with
      data from true null distributions. I also illustrate that it is extremely easy to
      introduce strong bias into data by very mild selection and re-testing. Similar,
      usually undocumented data dredging steps can easily lead to having 20-50%, or
      more false positives.

PMID- 27713724
TI  - Paranoia as an Antecedent and Consequence of Getting Ahead in Organizations: Time
      Lagged Effects Between Paranoid Cognitions, Self-Monitoring, and Changes in Span
      of Control.
AB  - A 6-month, time-lagged online survey among 441 employees in diverse industries
      was conducted to investigate the role paranoia plays as an antecedent and as a
      consequence of advancement in organizations. The background of the study is the
      argument that it requires active social sense-making and behavioral adaptability
      to advance in organizations. The present paper thus explores the extent to which
      employees' paranoid cognitions-representative of a heightened albeit suspicious
      sense-making and behavioral adaptability-link with their advancement in
      organizations (operationalized as changes in afforded span of control), both as
      an antecedent and an outcome. Following the strategy to illuminate the process by
      interaction analysis, both conditions (antecedent and outcome) are examined in
      interaction with employees' self-monitoring, which is considered representative
      of a heightened but healthy sense-making and behavioral adaptability. Results
      support the expected interference interaction between paranoid cognitions and
      self-monitoring in that each can to some degree compensate for the other in
      explaining employees' organizational advancement. Reversely, changes in span of
      control also affected paranoid cognitions. In particular, low self-monitors,
      i.e., those low in adaptive sense-making, reacted with heightened paranoid
      cognitions when demoted. In effect, the present study is thus the first to
      empirically support that paranoid cognitions can be a consequence but also a
      prerequisite for getting ahead in organizations. Practical advice should,
      however, be suspended until it is better understood whether and under what
      circumstances paranoia may relate not only to personally getting ahead but also
      to an increased effectiveness for the benefit of the organization.

PMID- 27713725
TI  - A Price Paid for Our Internal Strife: Escalated Intragroup Aggression and the
      Evolution of Ingroup Derogation.
AB  - From evolutionary reasoning, we derived a novel hypothesis that ingroup
      derogation is an adaptation to a special ecological condition in which the
      greater threat of aggression is incurred by ingroup members. This hypothesis was
      tested and supported across five studies. Specifically, the computational
      modeling found that ingroup derogation could easily evolve if the chance of death
      incurred by intragroup conflicts was no less than 10%. Further behavioral
      experiments on Chinese participants showed that the ingroup derogation mechanism
      responded to heuristic social category cues and it responded more strongly when
      participants subjectively felt more vulnerable to interpersonal aggression, or
      when there were contextual cues of aggression in the immediate environment.
      Additional results showed that Chinese participants responded more strongly to
      aggression cues originating from ingroup members and that they endorsed more
      ingroup derogation attitudes even when the ingroup and outgroup members were both
      displaying cues of aggression. In addition, the results also revealed that the
      Chinese participants perceived more intentions of aggression from ingroup members
      than from outgroup members even in the absence of any clear signs of those
      intentions, and such a bias was positively correlated with ingroup derogation
      attitudes. Taken together, these results suggest that ingroup derogation is
      related to the evolved response of intragroup aggression management system.

PMID- 27713726
TI  - Optimization of Xylanase Production through Response Surface Methodology by
      Fusarium sp. BVKT R2 Isolated from Forest Soil and Its Application in
      Saccharification.
AB  - Xylanses are hydrolytic enzymes with wide applications in several industries like
      biofuels, paper and pulp, deinking, food, and feed. The present study was aimed
      at hitting at high yield xylanase producing fungi from natural resources. Two
      highest xylanase producing fungal isolates-Q12 and L1 were picked from collection
      of 450 fungal cultures for the utilization of xylan. These fungal isolates-Q12
      and L1 were identified basing on ITS gene sequencing analysis as Fusarium sp.
      BVKT R2 (KT119615) and Fusarium strain BRR R6 (KT119619), respectively with
      construction of phylogenetic trees. Fusarium sp. BVKT R2 was further optimized
      for maximum xylanase production and the interaction effects between variables on
      production of xylanase were studied through response surface methodology. The
      optimal conditions for maximal production of xylanase were sorbitol 1.5%, yeast
      extract 1.5%, pH of 5.0, Temperature of 32.5 degrees C, and agitation of 175 rpm.
      Under optimal conditions, the yields of xylanase production by Fusarium sp. BVKT
      R2 was as high as 4560 U/ml in SmF. Incubation of different lignocellulosic
      biomasses with crude enzyme of Fusarium sp. BVKT R2 at 37 degrees C for 72 h
      could achieve about 45% saccharification. The results suggest that Fusarium sp.
      BVKT R2 has potential applications in saccharification process of biomass.

PMID- 27713727
TI  - Microbial Community Structure of Subglacial Lake Whillans, West Antarctica.
AB  - Subglacial Lake Whillans (SLW) is located beneath ~800 m of ice on the Whillans
      Ice Stream in West Antarctica and was sampled in January of 2013, providing the
      first opportunity to directly examine water and sediments from an Antarctic
      subglacial lake. To minimize the introduction of surface contaminants to SLW
      during its exploration, an access borehole was created using a microbiologically
      clean hot water drill designed to reduce the number and viability of
      microorganisms in the drilling water. Analysis of 16S rRNA genes (rDNA) amplified
      from samples of the drilling and borehole water allowed an evaluation of the
      efficacy of this approach and enabled a confident assessment of the SLW ecosystem
      inhabitants. Based on an analysis of 16S rDNA and rRNA (i.e., reverse-transcribed
      rRNA molecules) data, the SLW community was found to be bacterially dominated and
      compositionally distinct from the assemblages identified in the drill system. The
      abundance of bacteria (e.g., Candidatus Nitrotoga, Sideroxydans, Thiobacillus,
      and Albidiferax) and archaea (Candidatus Nitrosoarchaeum) related to
      chemolithoautotrophs was consistent with the oxidation of reduced iron, sulfur,
      and nitrogen compounds having important roles as pathways for primary production
      in this permanently dark ecosystem. Further, the prevalence of Methylobacter in
      surficial lake sediments combined with the detection of methanogenic taxa in the
      deepest sediment horizons analyzed (34-36 cm) supported the hypothesis that
      methane cycling occurs beneath the West Antarctic Ice Sheet. Large ratios of rRNA
      to rDNA were observed for several operational taxonomic units abundant in the
      water column and sediments (e.g., Albidiferax, Methylobacter, Candidatus
      Nitrotoga, Sideroxydans, and Smithella), suggesting a potentially active role for
      these taxa in the SLW ecosystem. Our findings are consistent with chemosynthetic
      microorganisms serving as the ecological foundation in this dark subsurface
      environment, providing new organic matter that sustains a microbial ecosystem
      beneath the West Antarctic Ice Sheet.

PMID- 27713728
TI  - Cell-Free Spent Media Obtained from Bifidobacterium bifidum and Bifidobacterium
      crudilactis Grown in Media Supplemented with 3'-Sialyllactose Modulate Virulence
      Gene Expression in Escherichia coli O157:H7 and Salmonella Typhimurium.
AB  - Complex oligosaccharides from human milk (HMO) possess an antimicrobial activity
      and can promote the growth of bifidobacteria such as Bifidobacterium bifidum and
      Bifidobacterium longum subsp. infantis. In addition, fermentation of
      carbohydrates by bifidobacteria can result in the production of metabolites
      presenting an antivirulence effect on several pathogenic bacteria. Whey is rich
      in complex bovine milk oligosaccharides (BMO) structurally similar to HMO and B.
      crudilactis, a species of bovine origin, is able to metabolize some of those
      complex carbohydrates. This study focused on the ability of B. bifidum and B.
      crudilactis to grow in a culture medium supplemented in 3'-sialyllactose (3'SL)
      as the main source of carbon, a major BMO encountered in cow milk. Next, the
      effects of cell-free spent media (CFSM) were tested against virulence expression
      of Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium. Both
      strains were able to grow in presence of 3'SL, but B. crudilactis showed the best
      growth (7.92 +/- 0.3 log cfu/ml) compared to B. bifidum (6.84 +/- 0.9 log
      cfu/ml). Then, CFSM were tested for their effects on virulence gene expression by
      ler and hilA promoter activity of luminescent mutants of E. coli and S.
      Typhimurium, respectively, and on wild type strains of E. coli O157:H7 and S.
      Typhimurium using RT-qPCR. All CFSM resulted in significant under expression of
      the ler and hilA genes for the luminescent mutants and ler (ratios of -15.4 and 
      8.1 respectively) and qseA (ratios of -2.1 and -3.1) for the wild type strain of
      E. coli O157:H7. The 3'SL, a major BMO, combined with some bifidobacteria strains
      of bovine or human origin could therefore be an interesting synbiotic to maintain
      or restore the intestinal health of young children. These effects observed in
      vitro will be further investigated regarding the overall phenotype of pathogenic
      agents and the exact nature of the active molecules.

PMID- 27713729
TI  - Pseudomonas fluorescens F113 Can Produce a Second Flagellar Apparatus, Which Is
      Important for Plant Root Colonization.
AB  - The genomic sequence of Pseudomonas fluorescens F113 has shown the presence of a
      41 kb cluster of genes that encode the production of a second flagellar
      apparatus. Among 2,535 pseudomonads strains with sequenced genomes, these genes
      are only present in the genomes of F113 and other six strains, all but one
      belonging to the P. fluorescens cluster of species, in the form of a genetic
      island. The genes are homologous to the flagellar genes of the soil bacterium
      Azotobacter vinelandii. Regulation of these genes is mediated by the flhDC master
      operon, instead of the typical regulation in pseudomonads, which is through fleQ.
      Under laboratory conditions, F113 does not produce this flagellum and the flhDC
      operon is not expressed. However, ectopic expression of the flhDC operon is
      enough for its production, resulting in a hypermotile strain. This flagellum is
      also produced under laboratory conditions by the kinB and algU mutants. Genetic
      analysis has shown that kinB strongly represses the expression of the flhDC
      operon. This operon is activated by the Vfr protein probably in a c-AMP dependent
      way. The strains producing this second flagellum are all hypermotile and present
      a tuft of polar flagella instead of the single polar flagellum produced by the
      wild-type strain. Phenotypic variants isolated from the rhizosphere produce this
      flagellum and mutation of the genes encoding it, results in a defect in
      competitive colonization, showing its importance for root colonization.

PMID- 27713730
TI  - High Iron-Sequestrating Bifidobacteria Inhibit Enteropathogen Growth and Adhesion
      to Intestinal Epithelial Cells In vitro.
AB  - The gut microbiota plays an important role in host health, in particular by its
      barrier effect and competition with exogenous pathogenic bacteria. In the present
      study, the competition of Bifidobacterium pseudolongum PV8-2 (Bp PV8-2) and
      Bifidobacterium kashiwanohense PV20-2 (Bk PV20-2), isolated from anemic infant
      gut microbiota and selected for their high iron sequestration properties, was
      investigated against Salmonella Typhimurium (S. Typhi) and Escherichia coli
      O157:H45 (EHEC) by using co-culture tests and assays with intestinal cell lines.
      Single and co-cultures were carried out anaerobically in chemically semi-defined
      low iron (1.5 MUM Fe) medium (CSDLIM) without and with added ferrous iron (30 MUM
      Fe). Surface properties of the tested strains were measured by bacterial adhesion
      to solvent xylene, chloroform, ethyl acetate, and to extracellular matrix
      molecules, mucus II, collagen I, fibrinogen, fibronectin. HT29-MTX mucus
      secreting intestinal cell cultures were used to study bifidobacteria competition,
      inhibition and displacement of the enteropathogens. During co-cultures in CSDLIM
      we observed strain-dependent inhibition of bifidobacterial strains on
      enteropathogens, independent of pH, organic acid production and supplemented
      iron. Bp PV8-2 significantly (P < 0.05) inhibited S. Typhi N15 and EHEC after 24
      h compared to single culture growth. In contrast Bk PV20-2 showed less inhibition
      on S. Typhi N15 than Bp PV8-2, and no inhibition on EHEC. Affinity for intestinal
      cell surface glycoproteins was strain-specific, with high affinity of Bp PV8-2
      for mucin and Bk PV20-2 for fibronectin. Bk PV20-2 showed high adhesion potential
      (15.6 +/- 6.0%) to HT29-MTX cell layer compared to Bp PV8-2 (1.4 +/- 0.4%). In
      competition, inhibition and displacement tests, Bp PV8-2 significantly (P < 0.05)
      reduced S. Typhi N15 and EHEC adhesion, while Bk PV20-2 was only active on S.
      Typhi N15 adhesion. To conclude, bifidobacterial strains selected for their high
      iron binding properties inhibited S. Typhi N15 and EHEC in co-culture experiments
      and efficiently competed with the enteropathogens on mucus-producing HT29-MTX
      cell lines. Further studies in complex gut ecosystems should explore host
      protection effects of Bp PV8-2 and Bk PV20-2 mediated by nutritional immunity
      mechanism associated with iron-binding.

PMID- 27713732
TI  - Armadillidin H, a Glycine-Rich Peptide from the Terrestrial Crustacean
      Armadillidium vulgare, Displays an Unexpected Wide Antimicrobial Spectrum with
      Membranolytic Activity.
AB  - Antimicrobial peptides (AMPs) are key components of innate immunity and are
      widespread in nature, from bacteria to vertebrate animals. In crustaceans, there
      are currently 15 distinct AMP families published so far in the literature, mainly
      isolated from members of the Decapoda order. Up to now, armadillidin is the sole
      non-decapod AMP isolated from the haemocytes of Armadillidium vulgare, a
      crustacean isopod. Its first description demonstrated that armadillidin is a
      linear glycine-rich (47%) cationic peptide with an antimicrobial activity
      directed toward Bacillus megaterium. In the present work, we report
      identification of armadillidin Q, a variant of armadillidin H (earlier known as
      armadillidin), from crude haemocyte extracts of A. vulgare using LC-MS approach.
      We demonstrated that both armadillidins displayed broad spectrum antimicrobial
      activity against several Gram-positive and Gram-negative bacteria, fungi, but
      were totally inactive against yeasts. Membrane permeabilization assays, only
      performed with armadillidin H, showed that the peptide is membrane active against
      bacterial and fungal strains leading to deep changes in cell morphology. This
      damaging activity visualized by electronic microscopy correlates with a rapid
      decrease of cell viability leading to highly blebbed cells. In contrast,
      armadillidin H does not reveal cytotoxicity toward human erythrocytes.
      Furthermore, no secondary structure could be defined in this study [by circular
      dichroism (CD) and nuclear magnetic resonance (NMR)] even in a membrane mimicking
      environment. Therefore, armadillidins represent interesting candidates to gain
      insight into the biology of glycine-rich AMPs.

PMID- 27713731
TI  - Genome-Based Genetic Tool Development for Bacillus methanolicus: Theta- and
      Rolling Circle-Replicating Plasmids for Inducible Gene Expression and Application
      to Methanol-Based Cadaverine Production.
AB  - Bacillus methanolicus is a thermophilic methylotroph able to overproduce amino
      acids from methanol, a substrate not used for human or animal nutrition. Based on
      our previous RNA-seq analysis a mannitol inducible promoter and a putative
      mannitol activator gene mtlR were identified. The mannitol inducible promoter was
      applied for controlled gene expression using fluorescent reporter proteins and a
      flow cytometry analysis, and improved by changing the -35 promoter region and by
      co-expression of the mtlR regulator gene. For independent complementary gene
      expression control, the heterologous xylose-inducible system from B. megaterium
      was employed and a two-plasmid gene expression system was developed. Four
      different replicons for expression vectors were compared with respect to their
      copy number and stability. As an application example, methanol-based production
      of cadaverine was shown to be improved from 11.3 to 17.5 g/L when a heterologous
      lysine decarboxylase gene cadA was expressed from a theta-replicating rather than
      a rolling-circle replicating vector. The current work on inducible promoter
      systems and compatible theta- or rolling circle-replicating vectors is an
      important extension of the poorly developed B. methanolicus genetic toolbox,
      valuable for genetic engineering and further exploration of this bacterium.

PMID- 27713733
TI  - Bacteriome-Localized Intracellular Symbionts in Pollen-Feeding Beetles of the
      Genus Dasytes (Coleoptera, Dasytidae).
AB  - Several insect taxa are associated with intracellular symbionts that provision
      limiting nutrients to their hosts. Such tightly integrated symbioses are
      especially common in insects feeding on nutritionally challenging diets like
      phloem sap or vertebrate blood, but also occur in seed-eating and omnivorous
      taxa. Here, we characterize an intracellular symbiosis in pollen-feeding beetles
      of the genus Dasytes (Coleoptera, Dasytidae). High-throughput tag-encoded 16S
      amplicon pyrosequencing of adult D. plumbeus and D. virens revealed a single
      gamma-proteobacterial symbiont ('Candidatus Dasytiphilus stammeri') that amounts
      to 52.4-98.7% of the adult beetles' entire microbial community. Almost complete
      16S rRNA sequences phylogenetically placed the symbiont into a clade comprising
      Buchnera and other insect endosymbionts, but sequence similarities to these
      closest relatives were surprisingly low (83.4-87.4%). Using histological
      examination, three-dimensional reconstructions, and fluorescence in situ
      hybridization, we localized the symbionts in three mulberry-shaped bacteriomes
      that are associated with the mid- to hind-gut transition in adult male and female
      beetles. Given the specialized pollen-feeding habits of the adults that contrasts
      with the larvae's carnivorous lifestyle, the symbionts may provision limiting
      essential amino acids or vitamins as in other intracellular symbioses, or they
      might produce digestive enzymes that break up the fastidious pollen walls and
      thereby contribute to the host's nutrition. In either case, the presence of gamma
      proteobacterial symbionts in pollen-feeding beetles indicates that intracellular
      mutualists are more widely distributed across insects with diverse feeding habits
      than previously recognized.

PMID- 27713734
TI  - The Highly Conserved Escherichia coli Transcription Factor YhaJ Regulates
      Aromatic Compound Degradation.
AB  - The aromatic compound 2,4-dinitrotoluene (DNT), a common impurity in 2,4,6
      trinitrotoluene (TNT) production, has been suggested as a tracer for the presence
      of TNT-based landmines due to its stability and high volatility. We have
      previously described an Escherichia coli bioreporter capable of detecting the
      presence of DNT vapors, harboring a fusion of the yqjF gene promoter to a
      reporter element. However, the DNT metabolite which is the direct inducer of
      yqjF, has not yet been identified, nor has the regulatory mechanism of the
      induction been clarified. We demonstrate here that the YhaJ protein, a member of
      the LysR type family, acts as a transcriptional regulator of yqjF activation, as
      well as of a panel of additional E. coli genes. This group of genes share a
      common sequence motif in their promoters, which is suggested here as a putative
      YhaJ-box. In addition, we have linked YhaJ to the regulation of quinol-like
      compound degradation in the cell, and identified yhaK as playing a role in the
      degradation of DNT.

PMID- 27713735
TI  - Modulation of the Bifidobacterial Communities of the Dog Microbiota by Zeolite.
AB  - During last decades canine health and well being is becoming an important issue
      for human owners. In dogs, several factors including diet, pathogenic bacterial
      and stress conditions can affect the composition of the gut microbiota. In this
      study, we evaluated the effect of dietary chabazitic zeolitite (CZ)
      supplementation on the contribution of bifidobacteria to the fecal microbiota in
      training hunting dogs. Fecal microbiota cataloging based on 16S rRNA microbial
      profiling analyses highlighted an increase of Lactobacillus and Bifidobacterium
      in animals treated with CZ, with a simultaneous decrease of pathogens associated
      with dog gastrointestinal infections, such as Klebsiella and Enterobacter. A
      detailed profiling of the bifidobacterial population of dogs receiving CZ based
      on the ITS-based sequencing approach, revealed an enhancement bifidobacterial of
      species typical of animals such as Bifidobacterium animalis and B. pseudolongum.
      Moreover, these analyses identified the occurrence of putative new
      bifidobacterial taxa in both treated and untreated samples.

PMID- 27713736
TI  - Identification and Characterization of an Aeromonas hydrophila Oligopeptidase
      Gene pepF Negatively Related to Biofilm Formation.
AB  - Bacterial biofilms are involved in adaptation to complex environments and are
      responsible for persistent bacterial infections. Biofilm formation is a highly
      complex process during which multifarious genes work together regularly. In this
      study, we screened the EZ-Tn5 transposon mutant library to identify genes
      involved in biofilm formation of Aeromonas hydrophila. A total of 24 biofilm
      associated genes were identified, the majority of which encoded proteins related
      to cell structure, transcription and translation, gene regulation, growth and
      metabolism. The mutant strain TM90, in which a gene encoding oligopeptidase F
      (pepF) was disturbed, showed significant upregulation of biofilm formation
      compared to the parental strain. The TM90 colony phenotype was smaller, more
      transparent, and splendent. The adhesive ability of TM90 to HEp-2 cells was
      significantly increased compared with the parental strain. Fifty percent lethal
      dose (LD50) determinations in zebrafish demonstrated that the enhanced-biofilm
      mutant TM90 was highly attenuated relative to the wild-type strain. In
      conclusion, the pepF gene is demonstrated for the first time to be a negative
      factor for biofilm formation and is involved in A. hydrophila pathogenicity.

PMID- 27713737
TI  - Development of a Method to Determine the Effectiveness of Cleaning Agents in
      Removal of Biofilm Derived Spores in Milking System.
AB  - Microbial damages caused by biofilm forming bacteria in the dairy industry are a
      fundamental threat to safety and quality of dairy products. In order to ensure
      the optimal level of equipment hygiene in the dairy industry, it is necessary to
      determine the biofilm removal efficiency of cleaning agents used for cleaning-in
      place (CIP) procedures. However, currently there is no standard method available
      for evaluating and comparing cleaning agents for use in CIP procedures in the
      dairy industry under realistic conditions. The present study aims to establish a
      CIP model system to evaluate the effectiveness of cleaning agents in removal of
      biofilm derived spores from the surfaces of stainless steel which is the
      predominant substrate in milking equipment on dairy farms. The system is based on
      Bacillus subtilis spores surrounded with exopolymeric substances produced by
      bacteria during biofilm formation. The spores applied on sampling plates were
      mounted on T-junctions protruding 1.5-11-times the milk pipe diameter from the
      main loop to resemble different levels of cleaning difficulty. The cleaning tests
      were conducted using commercial alkaline detergents and caustic soda at
      conditions which are relevant to actual farm environment. The spores removal
      effect was evaluated by comparing the number of viable spores (attached to
      sampling plates) before and after cleaning. Evaluation of the cleaning and
      disinfecting effect of cleaning agents toward biofilm derived spores was further
      performed, which indicates whether spores elimination effect of an agent is due
      to killing the spores or removing them from the surfaces of dairy equipment.
      Moreover, it was established that the presence of extracellular matrix is an
      important factor responsible for high level of cleaning difficulty characteristic
      for surface attached spores. In overall, the results of this study suggest that
      the developed model system simulates actual farm conditions for quantitative
      evaluation of the effectiveness of cleaning and disinfecting agents and their
      cleaning and disinfecting effect on removal of biofilm derived spores.

PMID- 27713738
TI  - Quantification of Virus Particles Using Nanopore-Based Resistive-Pulse Sensing
      Techniques.
AB  - Viruses have drawn much attention in recent years due to increased recognition of
      their important roles in virology, immunology, clinical diagnosis, and therapy.
      Because the biological and physical properties of viruses significantly impact
      their applications, quantitative detection of individual virus particles has
      become a critical issue. However, due to various inherent limitations of
      conventional enumeration techniques such as infectious titer assays,
      immunological assays, and electron microscopic observation, this issue remains
      challenging. Thanks to significant advances in nanotechnology, nanostructure
      based electrical sensors have emerged as promising platforms for real-time,
      sensitive detection of numerous bioanalytes. In this paper, we review recent
      progress in nanopore-based electrical sensing, with particular emphasis on the
      application of this technique to the quantification of virus particles. Our aim
      is to provide insights into this novel nanosensor technology, and highlight its
      ability to enhance current understanding of a variety of viruses.

PMID- 27713739
TI  - Quantification of Viral and Prokaryotic Production Rates in Benthic Ecosystems: A
      Methods Comparison.
AB  - Viruses profoundly influence benthic marine ecosystems by infecting and
      subsequently killing their prokaryotic hosts, thereby impacting the cycling of
      carbon and nutrients. Previously conducted studies, based on different
      methodologies, have provided widely differing estimates of the relevance of
      viruses on benthic prokaryotes. There has been no attempt so far to compare these
      independent approaches, including contextual comparisons among different
      approaches for sample manipulation (i.e., dilution or not of the sediments during
      incubations), between methods based on epifluorescence microscopy (EFM) or
      radiotracers, and between the use of different radiotracers. Therefore, it has
      been difficult to identify the most suitable methodologies and protocols to be
      used as standard approaches for the quantification of viral infections of
      prokaryotes. Here, we compared for the first time different methods for
      determining viral and prokaryotic production rates in marine sediments collected
      at two benthic sites, differing in depth and environmental conditions. We used a
      highly replicated experimental design, testing the potential biases associated to
      the incubation of sediments as diluted or undiluted. In parallel, we also
      compared EFM counts with the 3H-thymidine incubations for the determination of
      viral production rates, and the use of 3H-thymidine versus 3H-leucine
      radiotracers for the determination of prokaryotic production. We show here that,
      independent from sediment dilution, EFM-based values of viral production ranged
      from 1.4 to 4.6 * 107 viruses g-1 h-1, and were similar but overall less variable
      compared to those obtained by the 3H-thymidine method (0.3 to 9.0 * 107 viruses g
      1h-1). In addition, the prokaryotic production rates were not affected by
      sediment dilution, and the use of different radiotracers provided very consistent
      estimates (10.3-35.1 and 9.3-34.6 ngC g-1h-1 using the 3H-thymidine or 3H-leucine
      method, respectively). These results indicated that viral lysis was responsible
      for the abatement of 55-81% of the prokaryotic heterotrophic production,
      corroborating previous findings of the major role of viruses in benthic deep-sea
      ecosystems. Moreover, our methodological comparison for the analysis of viral
      production in marine sediments suggests that microscopy-based approaches are
      simpler and more cost-effective than those based on radiotracers. These
      approaches also reduce time to results and overcome issues related to generation
      of radioactive waste.

PMID- 27713741
TI  - Engineering of TM1459 from Thermotoga maritima for Increased Oxidative Alkene
      Cleavage Activity.
AB  - Oxidative cleavage of alkenes is a widely employed process allowing
      oxyfunctionalization to corresponding carbonyl compounds. Recently, a novel
      biocatalytic oxidative alkene cleavage activity on styrene derivatives was
      identified in TM1459 from Thermotoga maritima. In this work we engineered the
      enzyme by site-saturation mutagenesis of active site amino acids to increase its
      activity and to broaden its substrate scope. A high-throughput assay for the
      detection of the ketone products was successfully developed. Several variants
      with up to twofold improved conversion level of styrene derivatives were
      successfully identified. Especially, changes in or removal of the C-terminus of
      TM1459 increased the activity most significantly. These best variants also
      displayed a slightly enlarged substrate scope.

PMID- 27713743
TI  - Mastitis Pathogens with High Virulence in a Mouse Model Produce a Distinct
      Cytokine Profile In Vivo.
AB  - Mastitis is a serious medical condition of dairy cattle. Here, we evaluated
      whether the degree of virulence of mastitis pathogens in a mouse model can be
      linked to the inflammatory response that they provoke. Clinical isolates of
      Staphylococcus aureus (S. aureus) (strain 556 and 392) and Escherichia coli (E.
      coli) (676 and 127), and laboratory control strains [8325-4 (S. aureus) and
      MG1655 (E. coli)], were injected i.p. into mice, followed by the assessment of
      clinical scores and inflammatory parameters. As judged by clinical scoring, E.
      coli 127 exhibited the largest degree of virulence among the strains. All
      bacterial strains induced neutrophil recruitment. However, whereas E. coli 127
      induced high peritoneal levels of CXCL1, G-CSF, and CCL2, strikingly lower levels
      of these were induced by the less virulent bacterial strains. High concentrations
      of these compounds were also seen in blood samples taken from animals infected
      with E. coli 127, suggesting systemic inflammation. Moreover, the levels of CXCL1
      and G-CSF, both in the peritoneal fluid and in plasma, correlated with clinical
      score. Together, these findings suggest that highly virulent clinical mastitis
      isolates produce a distinct cytokine profile that shows a close correlation with
      the severity of the bacterial infection.

PMID- 27713742
TI  - PtrA Is Functionally Intertwined with GacS in Regulating the Biocontrol Activity
      of Pseudomonas chlororaphis PA23.
AB  - In vitro inhibition of the fungal pathogen Sclerotinia sclerotiorum by
      Pseudomonas chlororaphis PA23 is reliant upon a LysR-type transcriptional
      regulator (LTTR) called PtrA. In the current study, we show that Sclerotinia stem
      rot and leaf infection are significantly increased in canola plants inoculated
      with the ptrA-mutant compared to the wild type, establishing PtrA as an essential
      regulator of PA23 biocontrol. LTTRs typically regulate targets that are upstream
      of and divergently transcribed from the LTTR locus. We identified a short chain
      dehydrogenase (scd) gene immediately upstream of ptrA. Characterization of a scd
      mutant revealed that it is phenotypically identical to the wild type. Moreover,
      scd transcript abundance was unchanged in the ptrA mutant. These findings
      indicate that PtrA regulation does not involve scd, rather this LTTR controls
      genes located elsewhere on the chromosome. Employing a combination of
      complementation and transcriptional analysis we investigated whether connections
      exist between PtrA and other regulators of biocontrol. Besides ptrA, gacS was the
      only gene able to partially rescue the wild-type phenotype, establishing a
      connection between PtrA and the sensor kinase GacS. Transcriptomic analysis
      revealed decreased expression of biosynthetic (phzA, prnA) and regulatory genes
      (phzI, phzR, rpoS, gacA, rsmX, rsmZ, retS) in the ptrA mutant; conversely, rsmE,
      and rsmY were markedly upregulated. The transcript abundance of ptrA was nine
      fold higher in the mutant background indicating that this LTTR negatively
      autoregulates itself. In summary, PtrA is an essential regulator of genes
      required for PA23 biocontrol that is functionally intertwined with GacS.

PMID- 27713740
TI  - Stuck in the Middle: Fibronectin-Binding Proteins in Gram-Positive Bacteria.
AB  - Fibronectin is a multidomain glycoprotein found ubiquitously in human body fluids
      and extracellular matrices of a variety of cell types from all human tissues and
      organs, including intestinal epithelial cells. Fibronectin plays a major role in
      the regulation of cell migration, tissue repair, and cell adhesion. Importantly,
      fibronectin also serves as a common target for bacterial adhesins in the
      gastrointestinal tract. Fibronectin-binding proteins (FnBPs) have been identified
      and characterized in a wide variety of host-associated bacteria. Single bacterial
      species can contain multiple, diverse FnBPs. In pathogens, some FnBPs contribute
      to virulence via host cell attachment, invasion, and interference with signaling
      pathways. Although FnBPs in commensal and probiotic strains are not sufficient to
      confer virulence, they are essential for attachment to their ecological niches.
      Here we describe the interaction between human fibronectin and bacterial adhesins
      by highlighting the FnBPs of Gram-positive pathogens and commensals. We provide
      an overview of the occurrence and diversity of FnBPs with a focus on the model
      pathogenic organisms in which FnBPs are most characterized. Continued
      investigation of FnBPs is needed to fully understand their divergence and
      specificity in both pathogens and commensals.

PMID- 27713744
TI  - Peripheral and Central Neuroinflammatory Changes and Pain Behaviors in an Animal
      Model of Multiple Sclerosis.
AB  - Pain is a widespread and debilitating symptom of multiple sclerosis (MS), a
      chronic inflammatory demyelinating disease of the central nervous system.
      Although central neuroinflammation and demyelination have been implicated in MS
      related pain, the contribution of peripheral and central mechanisms during
      different phases of the disease remains unclear. In this study, we used the
      animal model experimental autoimmune encephalomyelitis (EAE) to examine both
      stimulus-evoked and spontaneous pain behaviors, and neuroinflammatory changes,
      over the course of chronic disease. We found that mechanical allodynia of the
      hind paw preceded the onset of clinical EAE but was unmeasurable at clinical
      peak. This mechanical hypersensitivity coincided with increased microglial
      activation confined to the dorsal horn of the spinal cord. The development of
      facial mechanical allodynia also emerged in preclinical EAE, persisted at the
      clinical peak, and corresponded with pathology of the peripheral trigeminal
      afferent pathway. This included T cell infiltration, which arose prior to overt
      central lesion formation and specific damage to myelinated neurons during the
      clinical peak. Measurement of spontaneous pain using the mouse grimace scale, a
      facial expression-based coding system, showed increased facial grimacing in mice
      with EAE during clinical disease. This was associated with multiple peripheral
      and central neuroinflammatory changes including a decrease in myelinating
      oligodendrocytes, increased T cell infiltration, and macrophage/microglia and
      astrocyte activation. Overall, these findings suggest that different pathological
      mechanisms may underlie stimulus-evoked and spontaneous pain in EAE, and that
      these behaviors predominate in unique stages of the disease.

PMID- 27713746
TI  - Estrous Cycle and Gestational Age-Dependent Expression of Members of the
      Interleukin-36 Subfamily in a Semi-Allogeneic Model of Infected and Non-Infected
      Murine Pregnancy.
AB  - The IL-36 subfamily is a recently described group of cytokines with pro
      inflammatory behavior, comprising three agonists (alpha, beta, and gamma), its
      receptor (R), and one antagonist (Ra). The expression and function of IL-36
      subfamily members in the estrous cycle in healthy and infected pregnancy has not
      been described. We evaluated mRNA and protein expression of IL-36 family members
      during the estrous cycle, implantation, fetal development, and post-labor periods
      in a model of allogenic pregnancy in mice. We also explored the ability of
      Listeria monocytogenes to modulate the expression of IL-36 subfamily members
      during pregnancy. Expression of IL-36 subfamily members showed different
      expression during the estrous cycle and pregnancy but was induced at estrous,
      16.5 days post coitum (dpc), 18.5 dpc, and labor. IL-36 subfamily members showed
      a characteristic distribution in the glandular epithelium, perimetrium,
      myometrium, and stratum vasculare. Infection with L. monocytogenes during
      pregnancy induced strong production of IL-36 subfamily members, an observation
      that correlated with an increasing prevalence of fetal loss. In conclusion, IL-36
      agonists showed specific patterns of mRNA and protein expression that might
      suggest functional specialization or specific target cells. Infection with L.
      monocytogenes during pregnancy induced strong production of IL-36 subfamily
      members.

PMID- 27713745
TI  - Phosphocholine-Specific Antibodies Improve T-Dependent Antibody Responses against
      OVA Encapsulated into Phosphatidylcholine-Containing Liposomes.
AB  - Liposomes containing phosphatidylcholine have been widely used as adjuvants.
      Recently, we demonstrated that B-1 cells produce dipalmitoyl-phosphatidylcholine
      (DPPC)-specific IgM upon immunization of BALB/c mice with DPPC-liposomes
      encapsulating ovalbumin (OVA). Although this preparation enhanced the OVA
      specific humoral response, the contribution of anti-DPPC antibodies to this
      effect was unclear. Here, we demonstrate that these antibodies are secreted by B
      1 cells independently of the presence of OVA in the formulation. We also confirm
      that these antibodies are specific for phosphocholine. The anti-OVA humoral
      response was partially restored in B-1 cells-deficient BALB/xid mice by
      immunization with the liposomes opsonized with the serum total immunoglobulin
      (Ig) fraction containing anti-phosphocholine antibodies, generated in wild-type
      animals. This result could be related to the increased phagocytosis by peritoneal
      macrophages of the particles opsonized with the serum total Ig or IgM fractions,
      both containing anti-phosphocholine antibodies. In conclusion, in the present
      work, it has been demonstrated that phosphocholine-specific antibodies improve T
      dependent antibody responses against OVA carried by DPPC-liposomes.

PMID- 27713747
TI  - Crosstalk between Wnt/beta-Catenin and NF-kappaB Signaling Pathway during
      Inflammation.
AB  - Besides its important role in embryonic development and homeostatic self-renewal
      in adult tissues, Wnt/beta-catenin signaling exerts both anti-inflammatory and
      proinflammatory functions. This is, at least partially, due to either repressing
      or enhancing the NF-kappaB pathway. Similarly, the NF-kappaB pathway either
      positively or negatively regulates Wnt/beta-catenin signaling. Different
      components of the two pathways are involved in this crosstalk, forming a complex
      regulatory network. This review summarizes our current understanding of the
      molecular mechanisms underlying the cross-regulation between the two pathways and
      discusses their involvement in inflammation and inflammation-associated diseases
      such as cancer.

PMID- 27713748
TI  - Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine
      Production and Slows Progression to Cancer.
AB  - Current treatment options for head and neck squamous cell carcinoma (HNSCC)
      patients are often ineffective due to tumor-localized and systemic
      immunosuppression. Using the 4-NQO mouse model of oral carcinogenesis, this study
      showed that premalignant oral lesion cells produce higher levels of the immune
      modulator, PGE2, compared to HNSCC cells. Inhibiting prostaglandin production of
      premalignant lesion cells with the pan-cyclooxygenase inhibitor indomethacin
      stimulated their induction of spleen cell cytokine production. In contrast,
      inhibiting HNSCC prostaglandin production did not stimulate their induction of
      spleen cell cytokine production. Treatment of mice bearing premalignant oral
      lesions with indomethacin slowed progression of premalignant oral lesions to
      HNSCC. Flow cytometric analysis of T cells in the regional lymph nodes of lesion
      bearing mice receiving indomethacin treatment showed an increase in lymph node
      cellularity and in the absolute number of CD8+ T cells expressing IFN-gamma
      compared to levels in lesion-bearing mice receiving diluent control treatment.
      The cytokine-stimulatory effect of indomethacin treatment was not localized to
      regional lymph nodes but was also seen in the spleen of mice with premalignant
      oral lesions. Together, these data suggest that inhibiting prostaglandin
      production at the premalignant lesion stage boosts immune capability and improves
      clinical outcomes.

PMID- 27713749
TI  - Genomic Dissection and Expression Profiling Revealed Functional Divergence in
      Triticum aestivum Leucine Rich Repeat Receptor Like Kinases (TaLRRKs).
AB  - The leucine rich repeat receptor like kinases (LRRK) constitute the largest
      subfamily of receptor like kinases (RLK), which play critical roles in plant
      development and stress responses. Herein, we identified 531 TaLRRK genes in
      Triticum aestivum (bread wheat), which were distributed throughout the A, B, and
      D sub-genomes and chromosomes. These were clustered into 233 homologous groups,
      which were mostly located on either homeologous chromosomes from various sub
      genomes or in proximity on the same chromosome. A total of 255 paralogous genes
      were predicted which depicted the role of duplication events in expansion of this
      gene family. Majority of TaLRRKs consisted of trans-membrane region and localized
      on plasma-membrane. The TaLRRKs were further categorized into eight phylogenetic
      groups with numerous subgroups on the basis of sequence homology. The gene and
      protein structure in terms of exon/intron ratio, domains, and motifs organization
      were found to be variably conserved across the different phylogenetic
      groups/subgroups, which indicated a potential divergence and neofunctionalization
      during evolution. High-throughput transcriptome data and quantitative real time
      PCR analyses in various developmental stages, and biotic and abiotic (heat,
      drought, and salt) stresses provided insight into modus operandi of TaLRRKs
      during these conditions. Distinct expression of majority of stress responsive
      TaLRRKs homologous genes suggested their specified role in a particular
      condition. These results provided a comprehensive analysis of various
      characteristic features including functional divergence, which may provide the
      way for future functional characterization of this important gene family in bread
      wheat.

PMID- 27713751
TI  - Comparative Evaluation of Biochemical Changes in Tomato (Lycopersicon esculentum
      Mill.) Infected by Alternaria alternata and Its Toxic Metabolites (TeA, AOH, and
      AME).
AB  - In the present study, we have evaluated the comparative biochemical defense
      response generated against Alternaria alternata and its purified toxins viz.
      alternariol (AOH), alternariol monomethyl ether (AME), and tenuazonic acid (TeA).
      The necrotic lesions developed due to treatment with toxins were almost similar
      as those produced by the pathogen, indicating the crucial role of these toxins in
      plant pathogenesis. An oxidative burst reaction characterized by the rapid and
      transient production of a large amount of reactive oxygen species (ROS) occurs
      following the pathogen infection/toxin exposure. The maximum concentration of
      hydrogen peroxide (H2O2) produced was reported in the pathogen infected samples
      (22.2-fold) at 24 h post inoculation followed by TeA (18.2-fold), AOH (15.9
      fold), and AME (14.1-fold) in treated tissues. 3,3'- Diaminobenzidine staining
      predicted the possible sites of H2O2 accumulation while the extent of cell death
      was measured by Evans blue dye. The extent of lipid peroxidation and
      malondialdehyde (MDA) content was higher (15.8-fold) at 48 h in the sample of
      inoculated leaves of the pathogen when compared to control. The cellular damages
      were observed as increased MDA content and reduced chlorophyll. The activities of
      antioxidative defense enzymes increased in both the pathogen infected as well as
      toxin treated samples. Superoxide dismutase (SOD) activity was 5.9-fold higher at
      24 h post inoculation in leaves followed by TeA (5.0-fold), AOH (4.1-fold) and
      AME (2.3-fold) treated leaves than control. Catalase (CAT) activity was found to
      be increased upto 48 h post inoculation and maximum in the pathogen challenged
      samples followed by other toxins. The native PAGE results showed the variations
      in the intensities of isozyme (SOD and CAT) bands in the pathogen infected and
      toxin treated samples. Ascorbate peroxidase (APx) and glutathione reductase (GR)
      activities followed the similar trend to scavenge the excess H2O2. The reduction
      in CAT activities after 48 h post inoculation demonstrate that the biochemical
      defense programming shown by the host against the pathogen is not well efficient
      resulting in the compatible host-pathogen interaction. The elicitor (toxins)
      induced biochemical changes depends on the potential toxic effects (extent of ROS
      accumulation, amount of H2O2 produced). Thus, a fine tuning occurs for the
      defense related antioxidative enzymes against detoxification of key ROS molecules
      and effectively regulated in tomato plant against the pathogen infected/toxin
      treated oxidative stress. The study well demonstrates the acute pathological
      effects of A. alternata in tomato over its phytotoxic metabolites.

PMID- 27713752
TI  - Using Deep Learning for Image-Based Plant Disease Detection.
AB  - Crop diseases are a major threat to food security, but their rapid identification
      remains difficult in many parts of the world due to the lack of the necessary
      infrastructure. The combination of increasing global smartphone penetration and
      recent advances in computer vision made possible by deep learning has paved the
      way for smartphone-assisted disease diagnosis. Using a public dataset of 54,306
      images of diseased and healthy plant leaves collected under controlled
      conditions, we train a deep convolutional neural network to identify 14 crop
      species and 26 diseases (or absence thereof). The trained model achieves an
      accuracy of 99.35% on a held-out test set, demonstrating the feasibility of this
      approach. Overall, the approach of training deep learning models on increasingly
      large and publicly available image datasets presents a clear path toward
      smartphone-assisted crop disease diagnosis on a massive global scale.

PMID- 27713750
TI  - Non-invasive Presymptomatic Detection of Cercospora beticola Infection and
      Identification of Early Metabolic Responses in Sugar Beet.
AB  - Cercospora beticola is an economically significant fungal pathogen of sugar beet,
      and is the causative pathogen of Cercospora leaf spot. Selected host genotypes
      with contrasting degree of susceptibility to the disease have been exploited to
      characterize the patterns of metabolite responses to fungal infection, and to
      devise a pre-symptomatic, non-invasive method of detecting the presence of the
      pathogen. Sugar beet genotypes were analyzed for metabolite profiles and
      hyperspectral signatures. Correlation of data matrices from both approaches
      facilitated identification of candidates for metabolic markers. Hyperspectral
      imaging was highly predictive with a classification accuracy of 98.5-99.9% in
      detecting C. beticola. Metabolite analysis revealed metabolites altered by the
      host as part of a successful defense response: these were L-DOPA, 12
      hydroxyjasmonic acid 12-O-beta-D-glucoside, pantothenic acid, and 5-O
      feruloylquinic acid. The accumulation of glucosylvitexin in the resistant
      cultivar suggests it acts as a constitutively produced protectant. The study
      establishes a proof-of-concept for an unbiased, presymptomatic and non-invasive
      detection system for the presence of C. beticola. The test needs to be validated
      with a larger set of genotypes, to be scalable to the level of a crop improvement
      program, aiming to speed up the selection for resistant cultivars of sugar beet.
      Untargeted metabolic profiling is a valuable tool to identify metabolites which
      correlate with hyperspectral data.

PMID- 27713753
TI  - The Woody-Preferential Gene EgMYB88 Regulates the Biosynthesis of Phenylpropanoid
      Derived Compounds in Wood.
AB  - Comparative phylogenetic analyses of the R2R3-MYB transcription factor family
      revealed that five subgroups were preferentially found in woody species and were
      totally absent from Brassicaceae and monocots (Soler et al., 2015). Here, we
      analyzed one of these subgroups (WPS-I) for which no gene had been yet
      characterized. Most Eucalyptus members of WPS-I are preferentially expressed in
      the vascular cambium, the secondary meristem responsible for tree radial growth.
      We focused on EgMYB88, which is the most specifically and highly expressed in
      vascular tissues, and showed that it behaves as a transcriptional activator in
      yeast. Then, we functionally characterized EgMYB88 in both transgenic Arabidopsis
      and poplar plants overexpressing either the native or the dominant repression
      form (fused to the Ethylene-responsive element binding factor-associated
      Amphiphilic Repression motif, EAR). The transgenic Arabidopsis lines had no
      phenotype whereas the poplar lines overexpressing EgMYB88 exhibited a substantial
      increase in the levels of the flavonoid catechin and of some salicinoid phenolic
      glycosides (salicortin, salireposide, and tremulacin), in agreement with the
      increase of the transcript levels of landmark biosynthetic genes. A change in the
      lignin structure (increase in the syringyl vs. guaiacyl, S/G ratio) was also
      observed. Poplar lines overexpressing the EgMYB88 dominant repression form did
      not show a strict opposite phenotype. The level of catechin was reduced, but the
      levels of the salicinoid phenolic glycosides and the S/G ratio remained
      unchanged. In addition, they showed a reduction in soluble oligolignols
      containing sinapyl p-hydroxybenzoate accompanied by a mild reduction of the
      insoluble lignin content. Altogether, these results suggest that EgMYB88, and
      more largely members of the WPS-I group, could control in cambium and in the
      first layers of differentiating xylem the biosynthesis of some phenylpropanoid
      derived secondary metabolites including lignin.

PMID- 27713754
TI  - Transcriptome Analysis of Sucrose Metabolism during Bulb Swelling and Development
      in Onion (Allium cepa L.).
AB  - Allium cepa L. is a widely cultivated and economically significant vegetable crop
      worldwide, with beneficial dietary and health-related properties, but its sucrose
      metabolism is still poorly understood. To analyze sucrose metabolism during bulb
      swelling, and the development of sweet taste in onion, a global transcriptome
      profile of onion bulbs was undertaken at three different developmental stages,
      using RNA-seq. A total of 79,376 unigenes, with a mean length of 678 bp, was
      obtained. In total, 7% of annotated Clusters of Orthologous Groups (COG) were
      involved in carbohydrate transport and metabolism. In the Kyoto Encyclopedia of
      Genes and Genomes (KEGG) database, "starch and sucrose metabolism" (147, 2.40%)
      constituted the primary metabolism pathway in the integrated library. The
      expression of sucrose transporter genes was greatest during the early-swelling
      stage, suggesting that sucrose transporters (SUTs) participated in sucrose
      metabolism mainly at an early stage of bulb development. A gene-expression
      analysis of the key enzymes of sucrose metabolism suggested that sucrose
      synthase, cell wall invertase, and invertase were all likely to participate in
      the hydrolysis of sucrose, generating glucose, and fructose. In addition,
      trehalose was hydrolyzed to two molecules of glucose by trehalase. From 15 to 40
      days after swelling (DAS), both the glucose and fructose contents of bulbs
      increased, whereas the sucrose content decreased. The growth rate between 15 and
      30 DAS was slower than that between 30 and 40 DAS, suggesting that the latter was
      a period of rapid expansion. The dataset generated by our transcriptome profiling
      will provide valuable information for further research.

PMID- 27713756
TI  - Effects of Selected Diazotrophs on Maize Growth.
AB  - Laboratory, greenhouse, and field experiments were conducted at the University of
      KwaZulu-Natal, Pietermaritzburg, South Africa in the 2010/2011 and 2011?2012
      seasons to study the effects of eight strains of diazotrophic bacteria on the
      growth and yield of maize. Maize seeds were treated with Bacillus megaterium
      (V16), Pseudomonas sp. (StB5, A3, A6, and A61), Burkholderia ambifaria (V9),
      Enterobacter cloacae (L1) and Pantoea ananatis (LB5), aiming to stimulate plant
      growth, and maintain or increase yields while reducing the need for N
      fertilization. All the diazotrophic bacteria increased germination of maize seed,
      and Pseudomonas sp. (StB5) and B. megaterium (V16) significantly increased shoot
      length. Pseudomonas sp. (StB5), B. megaterium (V16), E. cloacae (L1), B.
      ambifaria (V9), and Pseudomonas sp. (A3) very significantly increased root length
      and seed vigor index. Under greenhouse conditions, plants treated with
      diazotrophic bacteria developed more leaf chlorophyll and greater dry weight,
      albeit not significantly (n.s.). In a field trial in 2010/2011, application of
      the best five diazotrophic bacteria, with or without 33% N-fertilizer, had no
      significant effect on germination, grain yield, dry weight, plant height and leaf
      chlorophyll. In the 2011/2012 growing season, at 60 days after planting (DAP),
      all the diazotrophic bacteria increased plant dry weights to equal that of the
      fertilized control (33%N-fertilizer) (n.s.). After inoculation with the
      diazotrophs alone increased plant heights (n.s.), and chlorophyll contents
      (n.s.). With the addition of 33%N-fertilizer at planting, the diazotrophs still
      caused increases of chlorophyll content relative to the control with 33%N (n.s.).
      It may be concluded that the tested diazotrophs alone may be beneficial for use
      on maize growth.

PMID- 27713755
TI  - GUN1, a Jack-Of-All-Trades in Chloroplast Protein Homeostasis and Signaling.
AB  - The GENOMES UNCOUPLED 1 (GUN1) gene has been reported to encode a chloroplast
      localized pentatricopeptide-repeat protein, which acts to integrate multiple
      indicators of plastid developmental stage and altered plastid function, as part
      of chloroplast-to-nucleus retrograde communication. However, the molecular
      mechanisms underlying signal integration by GUN1 have remained elusive, up until
      the recent identification of a set of GUN1-interacting proteins, by co
      immunoprecipitation and mass-spectrometric analyses, as well as protein-protein
      interaction assays. Here, we review the molecular functions of the different GUN1
      partners and propose a major role for GUN1 as coordinator of chloroplast
      translation, protein import, and protein degradation. This regulatory role is
      implemented through proteins that, in most cases, are part of multimeric protein
      complexes and whose precise functions vary depending on their association states.
      Within this framework, GUN1 may act as a platform to promote specific functions
      by bringing the interacting enzymes into close proximity with their substrates,
      or may inhibit processes by sequestering particular pools of specific
      interactors. Furthermore, the interactions of GUN1 with enzymes of the
      tetrapyrrole biosynthesis (TPB) pathway support the involvement of tetrapyrroles
      as signaling molecules in retrograde communication.

PMID- 27713758
TI  - Commentary: Primary Transcripts of microRNAs Encode Regulatory Peptides.

PMID- 27713757
TI  - Gene Evolutionary Trajectories and GC Patterns Driven by Recombination in Zea
      mays.
AB  - Recombination occurring during meiosis is critical for creating genetic variation
      and plays an essential role in plant evolution. In addition to creating novel
      gene combinations, recombination can affect genome structure through altering GC
      patterns. In maize (Zea mays) and other grasses, another intriguing GC pattern
      exists. Maize genes show a bimodal GC content distribution that has been
      attributed to nucleotide bias in the third, or wobble, position of the codon.
      Recombination may be an underlying driving force given that recombination sites
      are often associated with high GC content. Here we explore the relationship
      between recombination and genomic GC patterns by comparing GC gene content at
      each of the three codon positions (GC1, GC2, and GC3, collectively termed GCx) to
      instances of a variable GC-rich motif that underlies double strand break (DSB)
      hotspots and to meiocyte-specific gene expression. Surprisingly, GCx bimodality
      in maize cannot be fully explained by the codon wobble hypothesis. High GCx genes
      show a strong overlap with the DSB hotspot motif, possibly providing a mechanism
      for the high evolutionary rates seen in these genes. On the other hand, genes
      that are turned on in meiosis (early prophase I) are biased against both high GCx
      genes and genes with the DSB hotspot motif, possibly allowing important meiotic
      genes to avoid DSBs. Our data suggests a strong link between the GC-rich motif
      underlying DSB hotspots and high GCx genes.

PMID- 27713759
TI  - Genome-Wide Differentiation of Various Melon Horticultural Groups for Use in GWAS
      for Fruit Firmness and Construction of a High Resolution Genetic Map.
AB  - Melon (Cucumis melo L.) is a phenotypically diverse eudicot diploid (2n = 2x =
      24) has climacteric and non-climacteric morphotypes and show wide variation for
      fruit firmness, an important trait for transportation and shelf life. We
      generated 13,789 SNP markers using genotyping-by-sequencing (GBS) and anchored
      them to chromosomes to understand genome-wide fixation indices (Fst) between
      various melon morphotypes and genomewide linkage disequilibrium (LD) decay. The
      FST between accessions of cantalupensis and inodorus was 0.23. The FST between
      cantalupensis and various agrestis accessions was in a range of 0.19-0.53 and
      between inodorus and agrestis accessions was in a range of 0.21-0.59 indicating
      sporadic to wide ranging introgression. The EM (Expectation Maximization)
      algorithm was used for estimation of 1436 haplotypes. Average genome-wide LD
      decay for the melon genome was noted to be 9.27 Kb. In the current research, we
      focused on the genome-wide divergence underlying diverse melon horticultural
      groups. A high-resolution genetic map with 7153 loci was constructed. Genome-wide
      segregation distortion and recombination rate across various chromosomes were
      characterized. Melon has climacteric and non-climacteric morphotypes and wide
      variation for fruit firmness, a very important trait for transportation and shelf
      life. Various levels of QTLs were identified with high to moderate stringency and
      linked to fruit firmness using both genome-wide association study (GWAS) and
      biparental mapping. Gene annotation revealed some of the SNPs are located in beta
      D-xylosidase, glyoxysomal malate synthase, chloroplastic anthranilate
      phosphoribosyltransferase, and histidine kinase, the genes that were previously
      characterized for fruit ripening and softening in other crops.

PMID- 27713760
TI  - Impact of Phenylpropanoid Compounds on Heat Stress Tolerance in Carrot Cell
      Cultures.
AB  - The phenylpropanoid and flavonoid families include thousands of specialized
      metabolites that influence a wide range of processes in plants, including seed
      dispersal, auxin transport, photoprotection, mechanical support and protection
      against insect herbivory. Such metabolites play a key role in the protection of
      plants against abiotic stress, in many cases through their well-known ability to
      inhibit the formation of reactive oxygen species (ROS). However, the precise role
      of specific phenylpropanoid and flavonoid molecules is unclear. We therefore
      investigated the role of specific anthocyanins (ACs) and other phenylpropanoids
      that accumulate in carrot cells cultivated in vitro, focusing on their supposed
      ability to protect cells from heat stress. First we characterized the effects of
      heat stress to identify quantifiable morphological traits as markers of heat
      stress susceptibility. We then fed the cultures with precursors to induce the
      targeted accumulation of specific compounds, and compared the impact of heat
      stress in these cultures and unfed controls. Data modeling based on projection to
      latent structures (PLS) regression revealed that metabolites containing coumaric
      or caffeic acid, including ACs, correlate with less heat damage. Further
      experiments suggested that one of the cellular targets damaged by heat stress and
      protected by these metabolites is the actin microfilament cytoskeleton.

PMID- 27713762
TI  - Assessment of CYP1A2 enzyme activity in relation to type-2 diabetes and habitual
      caffeine intake.
AB  - BACKGROUND: Coffee consumption is a known inducer of cytochrome P450 1A2 (CYP1A2)
      enzyme activity. We recently observed that a group of type-2 diabetes patients
      consumed more caffeine (coffee) on a daily basis than non-type-2 diabetes
      controls. Here, we investigated whether type-2 diabetes cases may metabolize
      caffeine faster than non-type-2 diabetes controls. METHODS: To estimate CYP1A2
      enzyme activity, an established marker of caffeine metabolism, we quantified the
      paraxanthine/caffeine concentration ratio in saliva in 57 type-2 diabetes and 146
      non-type-2 diabetes participants in a case-control field study. All participants
      completed validated questionnaires regarding demographic status, health and
      habitual caffeine intake, and were genotyped for the functional -163C > A
      polymorphism of the CYP1A2 gene. RESULTS: In the diabetes group, we found a
      larger proportion of participants with the highly inducible CYP1A2 genotype.
      Furthermore, the paraxanthine/caffeine ratio, time-corrected to mitigate the
      impact of different saliva sampling times with respect to the last caffeine
      intake, was higher than in the control group. Participants who reported
      habitually consuming more caffeine than the population average showed higher
      CYP1A2 activity than participants with lower than average caffeine consumption.
      Multiple regression analyses revealed that higher caffeine intake was potentially
      an important mediator of higher CYP1A2 activity. CONCLUSIONS: Estimated CYP1A2
      enzyme activity, and thus speed of caffeine metabolism, was higher in our type-2
      diabetes group; this was possibly due to higher intake of caffeine, a known
      inducer of CYP1A2 enzyme activity. Given the fairly small sample sizes, the
      results need to be considered as preliminary and require validation in larger
      populations.

PMID- 27713761
TI  - Genome-Wide Identification, Phylogeny, and Expression Analyses of the 14-3-3
      Family Reveal Their Involvement in the Development, Ripening, and Abiotic Stress
      Response in Banana.
AB  - Plant 14-3-3 proteins act as critical components of various cellular signaling
      processes and play an important role in regulating multiple physiological
      processes. However, less information is known about the 14-3-3 gene family in
      banana. In this study, 25 14-3-3 genes were identified from the banana genome.
      Based on the evolutionary analysis, banana 14-3-3 proteins were clustered into
      epsilon and non-epsilon groups. Conserved motif analysis showed that all
      identified banana 14-3-3 genes had the typical 14-3-3 motif. The gene structure
      of banana 14-3-3 genes showed distinct class-specific divergence between the
      epsilon group and the non-epsilon group. Most banana 14-3-3 genes showed strong
      transcript accumulation changes during fruit development and postharvest ripening
      in two banana varieties, indicating that they might be involved in regulating
      fruit development and ripening. Moreover, some 14-3-3 genes also showed great
      changes after osmotic, cold, and salt treatments in two banana varieties,
      suggested their potential role in regulating banana response to abiotic stress.
      Taken together, this systemic analysis reveals the involvement of banana 14-3-3
      genes in fruit development, postharvest ripening, and response to abiotic stress
      and provides useful information for understanding the functions of 14-3-3 genes
      in banana.

PMID- 27713763
TI  - In-hospital costs of an admission for adhesive small bowel obstruction.
AB  - BACKGROUND: Previous research on the costs of treatment for ASBO is outdated and
      often based on reimbursements, rather than true healthcare provider costs of the
      admission and related interventions. An accurate estimate of the true costs of
      treatment is necessary to understand the healthcare burden and to model cost
      efficacy of adhesion strategies. The aim of this study was to provide an accurate
      cost estimate of the in-hospital costs for treatment of adhesive small bowel
      obstruction (ASBO) using micro-costing methods. METHODS: Consecutive patients
      admitted for ASBO to the Radboud University Medical Center from November 2013 to
      November 2015 were included. An episode of ASBO was defined as an admission for
      SBO with operative confirmation of adhesions or after radiological exclusion of
      other causes for SBO. For the purpose of generalization we used the costs of
      medication and interventions as provided by the Dutch Healthcare Authority and
      only if these were not available local hospital costs. We evaluated costs
      separately for operative and non-operative treatment for ASBO. RESULTS: During
      the study period 39 admissions for ASBO were eligible for analysis. An operative
      treatment was required in 19 patients (48.7 %). Mean hospital stay for ASBO with
      operative treatment was 16.0 +/- 11 days versus 4.0 +/- 2.0 days for non
      operative treatment (P = 0.003). A total of 12 patients developed complications,
      2 in the non-operative group (10 %) and 10 in the operative group (52.6 %; P =
      0.004). Overall costs for an admission for ASBO with operative treatment were ?16
      305 (SD ?2 513), and for non-operative treatment ? 2 277 (SD ? 265) (p = <0.001).
      The highest expenditure with operative treatment for ASBO was made for ward stay
      (mean ?7 856, SD ?6 882), OR time (mean ?2 6845, SD ?1 434), ICU stay (mean ?2
      183, SD ?4 305) and (parenteral) feeding costs (mean ?1797, SD ?2070). A table
      with correction coefficient to correct for differences in price levels for goods
      and services between different countries has been added. CONCLUSION: The in
      hospital costs of an admission for ASBO are higher than previously thought. These
      costs can be used to guide hospital reimbursement policy and for the development
      of a cost-effective model for the use of adhesion barriers.

PMID- 27713766
TI  - Recalcitrant carbohydrates after enzymatic hydrolysis of pretreated
      lignocellulosic biomass.
AB  - BACKGROUND: To reduce the cost of the enzymes for the hydrolysis of
      lignocellulosic biomass, two main strategies have been followed: one, the
      reduction of enzyme dosing by the use of more efficient and stable enzymatic
      cocktails; another, to include accessory enzymes in the cocktails to increase
      yields by reducing the recalcitrant carbohydrate fraction remaining at the end of
      the process. To guide this second strategy, we have explored the chemical bond
      composition of different fractions of recalcitrant carbohydrates after enzymatic
      hydrolysis. RESULTS: Two lignocellulosic feedstocks of relevance for the biofuels
      industry have been analyzed, corn stover and sugarcane straw. On comparing the
      composition of chemical bonds of the starting pretreated material with samples
      after standard and forced hydrolysis (with enzyme overdosing), we obtained
      similar sugar and chemical bond composition. CONCLUSIONS: This suggests that the
      current enzymatic cocktails bear the set of enzymes needed to hydrolyze these
      feedstocks. From our point of view, the results show the need for a parallel fine
      tuning of the enzymatic cocktails with the pretreatment process to maximize sugar
      release yield.

PMID- 27713764
TI  - Cognitive and behavioral risk factors for child physical abuse among Chinese
      children: a multiple-informant study.
AB  - BACKGROUND: It has been well established that child physical abuse is a risk
      factor for cognitive deficits and behavioral problems. However, the possible link
      between cognitive deficits and behavioral problems placing children at a higher
      risk of physical abuse has been overlooked. Using a prospective design, the
      present study aims to examine whether previously measured cognition indicated by
      intelligence quotient (IQ), including performance IQ (PIQ) and verbal IQ (VIQ),
      and behavioral problems reported by multiple informants (i.e. mothers, teachers,
      and children) predict later child physical abuse (which may include minor and
      severe forms of abuse inflicted separately by mothers and fathers) in Chinese
      children. METHODS: A school-based survey was conducted to collect data from 265
      Chinese children (52.8 % boys, mean age 13.71 +/- 0.60 years) in the Wave II of
      China Jintan Cohort study. When they were in the last year of elementary school,
      children completed the Chinese version of the Wechsler intelligence scale for
      children-revised that measured VIQ and PIQ during 2010-2012 when their behaviors
      were self-assessed. Mothers and teachers of these children used the Chinese
      versions of the youth self report, the child behavior checklist and the teacher
      report form, respectively, to assess the children's behaviors. These children
      reported minor and severe physical abuse experiences in the previous 12 months
      from mothers and fathers separately using the Chinese version of parent-child
      conflict tactics scale in 2013 when children were in grades 7 and 8 of middle
      school. RESULTS: The present study found that after controlling for the
      sociodemographic and other cognitive and/or behavior variables, high scores of
      child externalizing behavior rated by their mothers or teachers were associated
      with increased risks of experiencing maternal and paternal severe physical abuse,
      while a high score of self-reported externalizing behavior was associated with a
      decreased risk of paternal severe physical abuse. A high score of mother-rated
      internalizing behavior was associated with a decreased risk of maternal severe
      physical abuse. VIQ was associated with maternal minor physical abuse with small
      effect size. PIQ was not associated with any forms of physical abuse after
      adjusting for child behavior and sociodemographic variables. CONCLUSIONS: In this
      community sample of Chinese children, externalizing behavior perceived by mothers
      and teachers is linked to children being at risk for physical abuse, while
      internalizing behavior perceived by mothers is associated with a decreased risk
      of maternal physical abuse. Findings suggest that educating parents and teachers
      to appropriately perceive children's externalizing behavior may help prevent the
      occurrence of physical abuse.

PMID- 27713765
TI  - Sleep and behavioural problems associate with low mood in Finnish children aged 4
      12 years: an epidemiological study.
AB  - BACKGROUND: Few studies have examined the associations between sleep, mood and
      behaviour in young children in the early stages of developing psychopathology.
      The purpose here was to examine the association of emotional problems, especially
      mood, with family and child characteristics, sleep and behavioural problems in 4
      12 year-old children. METHODS: The sample was population-based and included 1714
      children. Parents filled in the Strengths and Difficulties Questionnaire and a
      background questionnaire on child and family characteristics. The associations
      between (a) emotional symptoms/mood and background variables, (b) emotional
      problems and conduct problems/hyperactivity and (c) mood and conduct
      problems/hyperactivity were examined with ordinal regression in univariate and
      multivariate models. RESULTS: Of the background variables, child's sleeping
      problems had the most powerful association with emotional symptoms and mood.
      Abnormal emotional problems score and emotional symptoms were associated with
      abnormal conduct problems and hyperactivity scores. Of the emotional symptoms,
      low mood was the one associated most strongly with conduct problems and
      hyperactivity after controlling for all significant background variables and
      other emotional symptoms. CONCLUSIONS: We conclude that in young children sleep
      problems associate with low mood. Low mood associates with behavioural problems.
      When a child presents with low mood or behavioural problems, a comprehensive
      assessment of their psychiatric symptoms, as well as their sleep problems, is
      recommended.

PMID- 27713767
TI  - Prenatal diagnosis of 1p34.3 interstitial microdeletion by aCGH in a fetus with
      jaw bone abnormalities.
AB  - BACKGROUND: Interstitial microdeletions in 1p are extremely rare, as very few
      cases have been reported postnatally and only one prenatally, yet. There is a
      variability of phenotypic findings such as hypotonia, facial dysmorphisms, mild
      microcephaly, with being most common developmental delay. CASE PRESENTATION: The
      present case involved a female fetus with an interstitial deletion on 1p,
      presenting with micrognathia in the 2nd trimester routine ultrasound examination.
      Array-based comparative genomic hybridization (a-CGH) revealed a 2,7 Mb deletion
      located on 1p34.3 which could not be detected by standard karyotyping.
      CONCLUSIONS: This is the first prenatal case of an interstitial deletion in
      1p34.3 with facial dysmorphism detected by a-CGH. Due to the use of a-CGH
      techniques submicroscopic imbalances could be detected, and a refined genotype
      phenotype correlation could be achieved.

PMID- 27713768
TI  - Neurorehabilitation and Music.

PMID- 27713769
TI  - Stem cells and colorectal carcinogenesis.
AB  - Colorectal cancer represents an important cause of mortality and morbidity.
      Unfortunately, the physiopathology is still under study. There are theories about
      carcinogenesis and it is known that not only a single factor is responsible for
      the development of a tumor, but several conditions. Stem cells are a promising
      target for the treatment of colorectal cancer, along with the environment that
      has an important role. It has been postulated that mutations within the adult
      colonic stem cells may induce neoplastic changes. This theory is based on the
      observation that within a colon cancer, less than 1% of the neoplastic cells have
      the ability to regenerate the tumor and therefore they are responsible for
      recurrence. It is important to know that a new way of treatment needs to be
      found, since these cells are resistant to chemotherapy and radiotherapy.

PMID- 27713771
TI  - Iridociliary melanoma - Clinical case.
AB  - Iris and ciliary body melanoma is an aggressive tumor, which, unfortunately,
      presents symptoms only in advanced stages and is often discovered accidentally
      during a routine eye examination. There are several treatment options, ranging
      from in time monitorization in order to observe the tumor's evolution to more
      aggressive methods such as radiotherapy and enucleation. We present a case of
      iridociliary melanoma, who underwent conservative surgery, iridocyclectomy under
      scleral flap, with good results, and maintenance of the function and integrity of
      the eyeball.

PMID- 27713772
TI  - A new treatment approach - Eplerenone - in central serous chorioretinopathy -
      Case report.
AB  - We report the case of a 46-year-old patient, medical doctor with a relapsing
      unilateral CRSC-Central Serous Chorioretinopathy who was treated after an initial
      medical therapy (oral carbonic anhydrase inhibitor, oral antihistamines, non
      steroidal anti-inflammatory drugs - systemic and topical), with an oral
      aldosterone antagonist-Eplerenone (Inspra), resulted in significant anatomic and
      visual improvements. Abbreviations: CRSC = Central Serous Chorioretinopathy, R.E.
      = right eye, L.E. = left eye, BCVA = best corrected visual acuity, RPE = retinal
      pigment epithelium, OCT = optical coherence tomography, FDA = food and drug
      administration.

PMID- 27713770
TI  - The role of Vitamin D in immuno-inflammatory responses in Ankylosing Spondylitis
      patients with and without Acute Anterior Uveitis.
AB  - Hypothesis:Abnormal Vitamin D (Vit D) level could have consequences on the immuno
      inflammatory processes in Ankylosing Spondylitis (AS). Aim:The purpose of this
      study was to analyze the role of Vitamin D in the interplay between immune and
      inflammation effectors in AS associated-Acute Anterior Uveitis (AAU). Methods and
      Results:25-hydroxyvitamin D (Vit D), LL-37 peptide, IL-8 and Serum Amyloid A
      (SAA) were identified and quantified in the serum/ plasma of thirty-four AS
      patients [eleven AS patients presenting AAU (AAU AS patients) and twenty-three AS
      patients without AAU (wAAU AS patients)] and eighteen healthy individuals
      (Control) using enzyme-linked immunosorbent assay. Acute-phase SAA level was
      significantly higher in AS patients compared to Controls. Contrary with wAAU AS
      patients, significantly elevated levels of IL-8, and diminished levels of Vit D
      characterized AAU AS patients. Regarding LL-37, its level decreased concomitantly
      with the level of Vit D. When AS patients were subgrouped based on AAU presence
      or on Vit D level, important associations between immuno-inflammatory assessed
      markers and AS features were noticed. Generally, Vit D levels were associated
      indirectly with leukocytes/ neutrophils number or with ESR, CRP, and Fibrinogen
      levels. The levels of SAA and IL-8 associated directly with AAU or with AAU
      relapses, especially in AS patients with Vit D insufficiency, while SAA
      associated directly with infection/ inflammatory markers and with disease
      activity indexes or with the degree of functional limitation. Discussion:Altered
      levels of Vit D affect the balance between LL-37, IL-8 and SAA, suggesting an
      association with AAU, an extra-articular manifestation of AS. Abbreviations:Vit D
      = Vitamin D, AS = Ankylosing Spondylitis, AAU = Acute Anterior Uveitis, AAU AS =
      AS patients with AAU, wAAU AS = AS patients without AAU, SSZ = Sulphasalazine,
      Leu = Leukocytes, Neu = Neutrophils.

PMID- 27713773
TI  - Effect of diets supplemented with different conjugated linoleic acid (CLA)
      isomers on protein expression in C57/BL6 mice.
AB  - BACKGROUND: The individual genetic variations, as a response to diet, have
      recently caught the attention of several researchers. In addition, there is also
      a trend to assume food containing beneficial substances, or to supplement food
      with specific compounds. Among these, there is the conjugated linoleic acid
      (CLA), which has been demonstrated to reduce fat mass and to increase lean mass,
      even though its mechanism of action is still not known. We investigated the
      effect of CLA isomers (CLA c9,t11 and CLA t10,c12) on the proteomic profile of
      liver, adipose tissue, and muscle of mouse, with the aim of verifying the
      presence of a modification in fat and lean mass, and to explore the mechanism of
      action. METHODS: C57/BL6 mice were fed for 2 months with different diets: (1)
      standard chow, (2) CLA c9,t11 diet, (3) CLA t10,c11 diet, (4) CLA isomers mixture
      diet, and (5) linoleic acid diet. The proteomic profile of liver, white adipose
      tissue, and muscle was investigated. Statistical significance of the spots with
      an intensity higher than twofold in expression compared to the control was tested
      using student's t test (two-tail). RESULTS: We found that both isomers modulate
      the proteomic profiles of liver, adipose tissue, and muscle by different
      mechanisms of action. Liver steatosis is mostly due to the isomer CLA t10,c12,
      since it alters the expression of lipogenetic proteins; it acts also reducing the
      adipose tissue and increasing fatty acid oxidation in muscle. Conversely, CLA
      c9,t11 has no relevant effects on liver and adipose tissue, but acts mostly on
      muscle, where it enhances muscular cell differentiation. CONCLUSIONS:
      Administration of CLA in humans has to be carefully personalized, since even
      considering the presence of a species-specific effect, adverse effects might
      occur on long-term supplementation. Here we demonstrated that, in mouse, CLA is
      effective in reducing fat mass, but it also induces liver steatosis. The increase
      of lean mass is linked to an induction of cell proliferation, which, on long-term
      supplementation, might also lead to adverse effects.

PMID- 27713774
TI  - Alternative staging of regional lymph nodes in gastric cancer.
AB  - The TNM pN stage based on the number of metastatic lymph nodes is an independent
      prognostic factor in gastric cancer. Many studies have highlighted the phenomenon
      of stage migration and problems in comparing groups of patients with different
      numbers of total lymph nodes harvested within TNM staging. The current version of
      UICC/AJCC and JGCA TNM classifications postulates a minimal number of 16 lymph
      nodes as the base for N stage determination. Alternative systems such as lymph
      node ratio (LNR), positive to negative lymph node ratio (PNLNR), and LOGODDS (or
      LODDS), were implemented to increase the quality of LN assessment. These methods
      have reached the background in the literature, but to date no standard approach
      according to the cut-offs for the stages has been implemented. LOGODDS is the
      method that most reflects the number of harvested lymph nodes. The rationale for
      alternative staging methods, their correlations, and limitations are presented.

PMID- 27713775
TI  - Diet and Helicobacter pylori infection.
AB  - Helicobacter pylori infection has accompanied man for thousands of years. In some
      infected patients, a complex and dynamic pathogen-host reaction triggers
      pathogenic pathways resulting in development, inter alia, of atrophic gastritis,
      peptic ulcer disease (both gastric and duodenal), gastric adenocarcinoma, and
      MALT lymphoma. Large-scale eradication therapy is associated with a rapid
      increase in antibiotic resistance, gut flora composition disturbances, and
      increased risk of development, inter alia, of paediatric infectious diarrhoeas,
      atopic diseases, and oesophageal adenocarcinoma. Our diet contains many
      substances with potent antibacterial activity against H. pylori. Dietary
      interventions enable a decrease in H. pylori colonisation and result in a
      decrease in gastritis prevalence, thus potentially lowering the risk of gastric
      adenocarcinoma development.

PMID- 27713777
TI  - Clinical evaluation of double-channel gastroscope for endoscopic retrograde
      cholangiopancreatography in patients with Billroth II gastrectomy.
AB  - AIM: To evaluate the use of a double-channel gastroscope in patients with
      Billroth II gastrectomy to perform endoscopic retrograde cholangiopancreatography
      (ERCP) and interventions. MATERIAL AND METHODS: From January 2008 to December
      2013, 18 patients with Billroth II gastrectomy were enrolled in this study.
      Endoscopic retrograde cholangiopancreatography was performed using a straight
      forward gastroscope with double working channel (4.2-mm diameter, 2.8-mm
      diameter). RESULTS: The success rate of selective cannulation and accomplishment
      of planned procedures was 15 out of 18 patients (83.3%), and no serious
      complications were encountered. CONCLUSIONS: The double-channel gastroscope
      appears to be useful in performing endoscopic retrograde cholangiopancreatography
      in patients with Billroth II gastrectomy.

PMID- 27713778
TI  - A comparison of two methods of treatment for central catheter tunnel phlegmon in
      home parenteral nutrition patients.
AB  - INTRODUCTION: The ESPEN guidelines on long-term (> 3 months) parenteral nutrition
      recommend the use of tunnelled central venous catheters (CVCs) to minimise the
      risk of insertion site infection. A developed symptomatic infection of the soft
      tissue tunnel surrounding a CVC may rapidly become directly life threatening if
      the infection progresses along the catheter tunnel towards its end inserted into
      the venous system. This requires immediate management to eliminate infection and
      limit its effects. AIM: To compare two surgical techniques for the treatment of
      suppurative inflammation of a CVC tunnel: conventional drainage of the infected
      tissues (surgical technique A) vs. radical en bloc excision of the infected
      tissues together with the infected central catheter (surgical technique B).
      MATERIAL AND METHODS: Seventy-three patients hospitalised due to CVC tunnel
      phlegmon between April 2004 and May 2014 were included in the retrospective
      study. Thirty-four (46.5%) patients underwent surgical procedure A and another 39
      (53.5%) underwent procedure B. RESULTS: The mean duration of antibiotic therapy
      following procedure A was 8 +/-3 days, whereas procedure B required 7 +/-2 days
      of antibiotic therapy (NS). The mean hospitalisation period following procedure B
      was over 8 days shorter in comparison to that following procedure A (16.54 +/
      7.59 vs. 24.87 +/-10.19, p = 0.009, respectively). CONCLUSIONS: The surgical
      treatment of CVC tunnel phlegmon involving radical en bloc excision of suppurated
      tissues along with the infected CVC shortens hospitalisation, expedites the
      insertion of a new CVC, and potentially reduces treatment costs.

PMID- 27713776
TI  - Adjuvant, neoadjuvant, and experimental regimens in overcoming pancreatic ductal
      adenocarcinoma.
AB  - Pancreatic cancer is one of the most aggressive and deadly malignancies. Despite
      better understanding of its biology and pathogenesis, contemporary treatment
      regimens are still insufficient. Along with the introduction of new treatment
      agents and combination therapy, the response rates are increasing, but these
      scores do not go with overall survival, and results are frequently conflicting.
      Therefore, contemporary medicine faces the challenge of expanding the knowledge
      base and practice on all grounds - pathology, factor risk, diagnosis, and finally
      surgical and palliative treatment of this disease. This paper provides a review
      of current adjuvant and neoadjuvant regimens and the role of experimental
      therapies in pancreatic ductal adenocarcinoma.

PMID- 27713779
TI  - The impact of induction therapy with three doses of infliximab on deep
      histological healing in paediatric patients with active Crohn's disease.
AB  - INTRODUCTION: The clinical efficacy of infliximab (IFX) for induction of
      remission in both adults and children with active Crohn's disease (CD) has been
      well documented. Recently, so-called "deep remission" defined as mucosal healing
      has become the ultimate endpoint of the most recent therapeutic advances for CD.
      However, endoscopic evidence of mucosal healing is not necessarily associated
      with histological evidence of suppression of inflammation. AIM: Since data on
      that issue are limited, especially in the paediatric population, the aim of this
      study was to assess the impact of induction therapy with IFX on deep microscopic
      remission in paediatric patients with CD. MATERIAL AND METHODS: Fifty-six
      children (32 boys and 24 girls) aged 13.0 +/-9.3 years with moderate to severely
      active CD diagnosed at the mean age of 5.5 +/-0.83 years were included into the
      study. Colonoscopy and gastroscopy with sample collection were performed in all
      patients before and after three injections of IFX. Clinical activity of the
      disease was assessed using the Paediatric Crohn's Disease Activity Index (PCDAI),
      and the endoscopic activity was scored using the Simple Endoscopic Score (SES
      CD). Histological changes were evaluated by a previously described numerical
      scoring system. RESULTS: Thirty-nine (69.6%) patients reached clinical remission
      (PCDAI <= 10). When comparing data at baseline and at week 10, a significant
      decrease was observed in median PCDAI, and in SES-CD score between the initial
      and control colonoscopies. We also reported a decrease in histological scale.
      However, the difference was not statistically significant (p = 0.63). Three
      (5.4%) patients had a score of zero in the control histological examination. The
      correlation was found only between histological score and SES-CD score. Clinical
      remission correlated better with mucosal healing expressed by a decrease in SES
      CD score than with microscopic changes. CONCLUSIONS: Biological therapy with
      infliximab enables mucosal healing in paediatric patients with CD, which is not
      necessarily associated with histological evidence of suppression of inflammation.
      Mucosal healing correlates better than microscopic healing with clinical
      remission.

PMID- 27713780
TI  - Medium-chain triglycerides/long-chain triglycerides versus long-chain
      triglycerides in treatment of cancer patients with major body mass loss. Survival
      in patients with refractory cachexia.
AB  - INTRODUCTION: Currently there are no established guidelines regarding the use of
      long-chain triglycerides (LCT) vs. medium-chain triglycerides medium-chain
      triglycerides (MCT)/long-chain triglycerides (LCT) in total parenteral nutrition
      (TPN). Severe malnutrition of patients with refractory cachexia (RC) often causes
      their disqualification from invasive methods of treatment thus decreasing their
      quality of life and survival time. AIM: To compare the changes in nutritional
      state of patients with RC receiving PN with LCT and LCT/MCT lipid emulsions and
      to assess the influence of enteral nutrition on their survival time. MATERIAL AND
      METHODS: The study group comprised of 50 patients (23 female, 27 male) with a
      median age of 66 years. Refractory cachexia was diagnosed in them due to
      dysphagia secondary to solid tumours causing obstruction of the gastrointestinal
      tract (GT). All patients were qualified for surgical gastrostomy due to
      contraindications to percutaneous endoscopic gastrostomy. The patients were
      randomly assigned into one of two groups and perioperatively received either LCT
      or LCT/MCT. Blood samples were collected four times and tested for: total
      protein, albumin, prealbumin, and C-reactive protein concentration. Patients
      received Home Enteral Nutrition after discharge from hospital. RESULTS: Changes
      in nutritional status parameters were similar among patients receiving lipid
      emulsions LCT vs. MCT/LCT in TPN for 11 days. The mean survival time of all
      patients operated to gain enteral access to nutrition was 192 +/-268 days, and
      the median survival was 98 days. CONCLUSIONS: Regarding the short-term TPN, the
      results of the study do not demonstrate any superiority of MCT/LCT lipid
      emulsions over LCT, or vice versa. The inability to eat significantly accelerates
      unintended body mass loss among patients with RC. Disqualification from invasive
      treatment options deprives some patients of the benefits they might have obtained
      from the surgical access to GT and enteral nutrition.

PMID- 27713781
TI  - Intestinal healing after anti-TNF induction therapy predicts long-term response
      to one-year treatment in patients with ileocolonic Crohn's disease naive to anti
      TNF agents.
AB  - INTRODUCTION: Objective assessment of Crohn's disease (CD) activity in patients
      treated with anti-tumour necrosis factor (anti-TNF) antibodies is crucial for the
      prediction of its long-term results. Mucosal healing estimated endoscopically has
      a strong predictive value; however, only combined assessment together with
      transmural healing in magnetic resonance enterography (MRE) gives full
      information about the whole spectrum of inflammatory lesions in CD. AIM: To
      assess the usefulness of intestinal healing phenomenon in CD, defined as
      improvement both in endoscopy and MRE, after anti-TNF induction therapy, in
      predicting long-term results of 1-year treatment. MATERIAL AND METHODS: Twenty
      six patients with ileocolonic CD were enrolled into the study. In this group a
      parallel assessment of disease activity was estimated before and after induction
      doses of anti-TNF antibodies with ileocolonoscopy and MRE by using appropriate
      scores. Subsequently the patients were treated until 12 months and then followed
      up. The associations between intestinal healing (assessed in MRE and endoscopy),
      and mucosal and transmural healing with long-term results of 1-year anti-TNF
      therapy were analysed statistically. RESULTS: The median time of follow-up was 29
      months (interquartile range - IQR: 14-46). Intestinal healing was significantly
      associated with favourable therapeutic outcomes (p = 0.02) and had 75% (IQR: 35
      97%) sensitivity and 72% (IQR: 46-90%) specificity in predicting long-term
      remission. Other parameters were not useful (transmural healing) or their
      usefulness was of borderline significance (mucosal healing). CONCLUSIONS: Dynamic
      assessment of intestinal healing is an accurate method in predicting long-term
      outcomes in CD patients responding to 1-year anti-TNF therapy.

PMID- 27713782
TI  - Endoscopic therapy of oesophageal strictures in children - a multicentre study.
AB  - INTRODUCTION: Oesophageal strictures are rare in children but may require
      endoscopic dilation. AIM: To gather information on centres performing endoscopic
      oesophageal dilation in Poland. MATERIAL AND METHODS: The data were obtained from
      questionnaires concerning the relevant data mailed to 22 paediatric endoscopy
      centres. Completed questionnaires were received from 11 centres. RESULTS: In 2010
      the 11 Polish paediatric endoscopy centres performed a total of 10,650 endoscopic
      procedures. This included 347 oesophageal dilations in 106 paediatric patients
      aged from 1 month to 18 years. The numbers of patients treated at individual
      centres ranged from 2 to 40. The indications for oesophageal dilation were as
      follows: postoperative strictures in 68 children, oesophageal burns in 17
      children, postinflammatory strictures in 14 children, achalasia in 4 children,
      and strictures caused by a foreign body in 3 children. Rigid guidewire dilators
      were used in the majority of procedures (271), rigid dilators without a guidewire
      in 32 procedures, and balloon dilators in 45 procedures. A total of 203
      procedures were conducted under fluoroscopic guidance, and 144 without the use of
      fluoroscopy. The number of dilating sessions performed in individual children
      varied from 1 to 6 and more. CONCLUSIONS: Oesophageal dilation constituted a
      minor proportion of all paediatric endoscopic procedures. The majority of
      children requiring dilation were patients up to 3 years of age with postoperative
      oesophageal strictures. In the majority of the centres rigid guidewire dilators
      were used, and in one third of the procedures these dilators were introduced
      without fluoroscopic guidance.

PMID- 27713783
TI  - The effect of standard therapy on mean platelet volume in patients with chronic
      hepatitis C.
AB  - INTRODUCTION: Chronic hepatitis C (CHC) infection is a systemic disorder that can
      lead to liver inflammation, fibrosis, cirrhosis, and hepatocellular cancer. The
      mean platelet volume (MPV) is widely used as an inflammatory marker to evaluate
      the platelet function and the status of systemic inflammation. AIM: To determine
      the pre- and post-treatment MPV values in CHC patients who were administered a 48
      week antiviral therapy based on systemic inflammation. MATERIAL AND METHODS: We
      enrolled 28 patients, diagnosed with CHC genotype 1b, who received a 48-week
      antiviral therapy and attended regular follow-up, and 28 healthy individuals. In
      diagnosing CHC, a positive anti-HCV for a minimum duration of 6 months and a
      positive serum HCV RNA were accepted as the criteria. The patients were assigned
      to one of two groups based on their group 1 (pre-treatment values) and group 2
      (post-treatment values) after 3 months therapy. We analysed and compared the
      blood samples of all of the groups. RESULTS: The MPV value was 8.89 +/-1.20 in
      group 1 and 8.00 +/-1.07 in group 2, and 8.21 +/-1.18 in the control group. The
      value in group 1 was detected to be statistically significantly different from
      that in group 2 and the control group (p < 0.0001, p = 0.045, respectively). No
      statistically significant difference was observed between group 2 and the control
      group (p = 0.455). CONCLUSIONS: The results of this study suggest that MPV could
      represent an inexpensive marker for use in assessing low-grade inflammation in
      patients with CHC.

PMID- 27713784
TI  - Cyanoacrylate application on colonic anastomosis: is it safe or not?
AB  - INTRODUCTION: Major complications of colonic anastomosis include fistula,
      bleeding, and anastomotic stricture, and the most common one is anastomotic
      leakage. Many organic or inorganic tissue adhesives are being used such as fibrin
      glue or cyanoacrylate to strengthen or protect colonic anastomosis. Up to now, a
      great number of studies have been carried out to investigate the effects of these
      biomaterials. AIM: To determine the effect of cyanoacrylate application on
      anastomosis safety. MATERIAL AND METHODS: In this experimental study, rats were
      divided into two groups; a control group and an experimental group. Full
      thickness incisions were done on the left colon of the rats, and then end-to-end
      anastomosis was performed by using 5/0 silk separated sutures. In the
      experimental group we applied cyanoacrylate over the sutures. The samples were
      taken on the 7th day. RESULTS: In the control group the average tissue
      hydroxyproline levels and the average bursting pressures were significantly
      higher than in the experimental group. CONCLUSIONS: The purpose of all the
      experimental studies is to prevent and reduce anastomotic complications. Despite
      all the studies that have been done, colonic anastomosis complications continue
      to be a problem. As a result, we suggest that cyanoacrylate has a negative effect
      on the healing process of colonic anastomosis.

PMID- 27713785
TI  - A giant non-functioning pancreatic neuroendocrine carcinoma founded as an
      incidentaloma successfully treated with pancreatoduodenectomy.

PMID- 27713786
TI  - Diagnostic imaging of a solid pseudopapillary tumour of the pancreas in a 20-year
      old woman - a case study.

PMID- 27713788
TI  - Addressing concerns around the veracity of scientific research and publication.

PMID- 27713789
TI  - A parting message and a look toward the future.

PMID- 27713787
TI  - Extraintestinal manifestations of Crohn's disease.

PMID- 27713790
TI  - Mapping a competency-based surgical curriculum in urology: Agreement (and
      discrepancies) in the Canadian national opinion.
AB  - INTRODUCTION: Urology residency training in Canada is quickly evolving from a
      time-based to a competency-based model. We aim to better define core surgical
      competencies that would comprise a surgical curriculum and assess any
      discrepancies in opinion nationally. METHODS: A web-based survey was validated
      and sent to the 536 practicing members of the Canadian Urological Association
      (CUA) in August and October 2014. The survey consisted of questions regarding
      practice demographics, fellowship training, and evaluated the 76 most common
      urological procedures (using a five-point Likert scale) in the context of the
      question, "After completion of residency training in Canada a urologist should be
      proficient in..." A core procedure was defined as one for which there was >=75%
      agreement. Descriptive statistics and non-parametric testing were used to
      summarize the findings. RESULTS: A total of 138 urologists completed the survey
      (25.7% response rate) with representation from all geographic regions.
      Respondents included 40.6% community and 59.4% academic urologists. The survey
      identified 16 procedures with 90-100% agreement and a total of 30 core procedures
      with >=75% agreement. When comparing community and academic urologists, there was
      statistically significant disagreement on 27 procedures, including 11 core
      procedures, most notably cystectomy (88.5% agreement vs. 67.1%; p=0.002), open
      pyeloplasty (84.6% vs. 65.8%; p=0.04), simple prostatectomy (78.9% vs. 69.7%;
      p=0.03), perineal urethrostomy (80.8% vs. 67.1%; p=0.02), open radical
      prostatectomy (96.1% vs. 80.3%; p=0.007), and Boari flap (90.4% vs. 76.3%;
      p=0.004). Regional discrepancies were also found, demonstrating eight procedures
      deemed uniquely core and three core procedures deemed less important regionally.
      CONCLUSIONS: This national survey has provided some consensus on 30 procedures
      that should comprise a core surgical curriculum in urology. However, there are
      some key differences of opinion (most notably between community and academic
      urologists) that must be considered.

PMID- 27713792
TI  - CUA brochure readability: On the right track.

PMID- 27713791
TI  - An analysis of the readability of patient information materials for common
      urological conditions.
AB  - INTRODUCTION: Health literacy has been shown to be an important determinant of
      outcomes in numerous disease states. In an effort to improve health literacy, the
      Canadian Urological Association (CUA) publishes freely accessible patient
      information materials (PIMs) on common urological conditions. We sought to
      evaluate the readability of the CUA's PIMs. METHODS: All PIMs were accessed
      through the CUA website. The Flesch Reading Ease Score (FRES), the Flesch-Kincaid
      Grade Level (FKGL), and the number of educational graphics were determined for
      each PIM. Low FRES scores and high FKGL scores are associated with more difficult
      to-read text. Average readability values were calculated for each PIM category
      based on the CUA-defined subject categorizes. The five pamphlets with the highest
      FKGL scores were revised using word substitutions for complex multisyllabic words
      and reanalyzed. The Kruskal-Wallis test was used to identify readability
      differences between PIM categories and paired t-tests were used to test
      differences between FKGL scores before and after revisions. RESULTS: Across all
      PIMs, FRES values were low (mean 47.5, standard deviation [SD] 7.47). This
      corresponded to an average FKGL of 10.5 (range 8.1-12.0). Among PIM categories,
      the infertility and sexual function PIMs exhibited the highest average FKGL (mean
      11.6), however, differences in scores between categories were not statistically
      significant (p=0.38). The average number of words per sentence was also highest
      in the infertility and sexual function PIMs and significantly higher than other
      categories (mean 17.2; p=0.01). On average, there were 1.4 graphics displayed per
      PIM (range 0-4), which did not vary significantly by disease state (p=0.928).
      Simple words substitutions improved the readability of the five most difficult-to
      read PIMs by an average of 3.1 grade points (p<0.01). CONCLUSIONS: Current
      patient information materials published by the CUA compare favourably to those
      produced by other organizations, but may be difficult to read for low-literacy
      patients. Readability levels must be balanced against the required informational
      needs of patients, which may be intrinsically complex.

PMID- 27713793
TI  - The impact of teaching on the duration of common urological operations.
AB  - INTRODUCTION: The ability of academic (teaching) hospitals to offer the same
      level of efficiency as non-teaching hospitals in a publicly funded healthcare
      system is unknown. Our objective was to compare the operative duration of general
      urology procedures between teaching and non-teaching hospitals. METHODS: We used
      administrative data from the province of Ontario to conduct a retrospective
      cohort study of all adults who underwent a specified elective urology procedure
      (2002-2013). Primary outcome was duration of surgical procedure. Primary exposure
      was hospital type (academic or non-teaching). Negative binomial regression was
      used to adjust relative time estimates for age, comorbidity, obesity, anesthetic,
      and surgeon and hospital case volume. RESULTS: 114 225 procedures were included
      (circumcision n=12 280; hydrocelectomy n=7221; open radical prostatectomy n=22
      951; transurethral prostatectomy n=56 066; or mid-urethral sling n=15 707). These
      procedures were performed in an academic hospital in 14.8%, 13.3%, 28.6%, 17.1%,
      and 21.3% of cases, respectively. The mean operative duration across all
      procedures was higher in academic centres; the additional operative time ranged
      from 8.3 minutes (circumcision) to 29.2 minutes (radical prostatectomy). In
      adjusted analysis, patients treated in academic hospitals were still found to
      have procedures that were significantly longer (by 10-21%). These results were
      similar in sensitivity analyses that accounted for the potential effect of more
      complex patients being referred to tertiary academic centres. CONCLUSIONS: Five
      common general urology operations take significantly longer to perform in
      academic hospitals. The reason for this may be due to the combined effect of
      teaching students and residents or due to inherent systematic inefficiencies
      within large academic hospitals.

PMID- 27713794
TI  - Slower but safe? Resident involvement in urological surgeries.

PMID- 27713795
TI  - A survey of Canadian urologists' opinions and prescribing patterns of
      testosterone replacement therapy in men on active surveillance for low-risk
      prostate cancer.
AB  - INTRODUCTION: Attitudes regarding the safety of testosterone replacement therapy
      (TRT) in hypogonadal men with prostate cancer (PCa) have changed over the past
      few years with the emergence of case studies suggesting a low risk of cancer
      progression and a better understanding of the interaction of different levels of
      androgen with prostate cellular metabolism. This new view has the potential to
      change clinical practice. METHODS: Active members of the Canadian Urological
      Association were surveyed about their opinions on the safety of TRT in men with
      low-risk PCa, as well as their current prescribing habits. RESULTS: Of 57
      responding urologists, 86% actively prescribe TRT in men with testosterone
      deficiency syndrome (TDS), 93% are involved in the treatment of men with PCa, and
      95% offer active surveillance as a management option for low-grade/low-stage
      disease. Furthermore, 65% stated that they would offer TRT to men with TDS who
      were on active surveillance for PCa and 63% believed that TRT did not increase
      the risk of progression of PCa in these men. In terms of treatment methods, 96%
      believed TRT was safe for men who have undergone radical prostatectomy, while a
      smaller number felt it was safe for patients who have undergone brachytherapy
      (86%) or external beam radiation (84%). Despite these figures, only 35% of the
      surveyed physicians had ever offered TRT for men on active surveillance and only
      42% actually had men in their practice who were taking testosterone while on
      active surveillance. CONCLUSIONS: The discrepancy between urologists' beliefs
      about the safety of TRT and their clinical practice patterns may be due to
      multiple factors, such as hesitation in recommending treatment in real-life
      practice, low numbers of eligible patients, absence of screening for testosterone
      deficiency in patients on active surveillance, and patient preference or fears.
      Furthermore, the difference in perceived safety in men treated by radical
      prostatectomy vs. radiation therapy suggests that some urologists are concerned
      that the radiated gland remaining in-situ may be "reactivated" by TRT. The
      results from this survey will be used as the basis of developing a national
      Canadian registry of men with low-grade/stage PCa who are receiving TRT while on
      active surveillance.

PMID- 27713796
TI  - Addressing the pressing issues related to testosterone administration to men with
      prostate cancer.

PMID- 27713798
TI  - Well-trained staff is the key to the success of urodynamic testing.

PMID- 27713797
TI  - Trained and dedicated staff appears to be the main factor in decreasing anxiety
      and improving overall satisfaction during urodynamic testing: A prospective,
      randomized trial.
AB  - INTRODUCTION: We sought to determine whether listening to patient-selected music
      during urodynamic study (UDS) reduced pain and anxiety while increasing overall
      patient satisfaction and willingness to repeat the procedure. METHODS: Fifty-one
      (51) patients who underwent UDS from March to July 2014 were randomized into two
      groups: Group 1 with patient-selected music during the procedure (n=27) and Group
      2 without music (n=24). Standard multichannel filling cystometry was performed.
      Anxiety was self-assessed using the State Trait Anxiety Inventory, while overall
      pain, satisfaction, and willingness to undergo the procedure again were self
      measured using a visual analogue scale. RESULTS: Demographic characteristics and
      reasons for testing were similar between the two groups. The state score for
      Groups 1 and 2 were 27.04 and 29.5, respectively (p=0.3225) and 31.78 and 33.86,
      respectively (p=0.4970) for the trait score. The mean pain scores were 1.04 and
      1.57, respectively (p=0.2047); the mean satisfaction scores were 0.65 and 0.52,
      respectively (p=0.8169); and the scores for willingness to undergo the procedure
      again were 0.77 and 0.74, respectively (p=0.9442). While there were no
      significant differences between the two groups in anxiety and satisfaction
      scores, pain, and willingness to undergo the procedure again, both groups
      commented on the nurse as the most important factor in their overall comfort.
      CONCLUSIONS: Music during UDS did not appear to lower pain and anxiety, nor
      increase overall satisfaction and willingness to repeat the procedure. The most
      important aspect in alleviating patients' pain and anxiety was the person
      actually performing the testing, highlighting the importance of having trained
      and dedicated staff.

PMID- 27713800
TI  - Robotic prostatectomy and access to care: Canadian vs. U.S. experience.

PMID- 27713799
TI  - Robotic prostatectomy is associated with increased patient travel and treatment
      delay.
AB  - INTRODUCTION: New technologies may limit access to treatment. We investigated
      radical prostatectomy (RP) access over time since robotic introduction and the
      impact of robotic use on RP access relative to other approaches in the modern
      era. METHODS: Using the National Cancer Data Base, RPs performed during the eras
      of early (2004-2005) and late (2010-2011) robotic dissemination were identified.
      The primary endpoints, patient travel distance and treatment delay, were compared
      by era, and for 2010-2011, by surgical approach. Analyses included multivariable
      and multinomial logistic regression. RESULTS: 138 476 cases were identified, 32%
      from 2004-2005 and 68% from 2010-2011. In 2010-2011, 74%, 21%, and 4.3% of RPs
      were robotic, open, and laparoscopic, respectively. Treatment in 2010-2011 and
      robotic approach were independently associated with increased patient travel
      distance and longer treatment delay (p<0.001). Men treated robotically had 1.1
      1.2 times higher odds of traveling medium-to-long-range distances and 1.2-1.3
      higher odds of delays 90 days or greater compared to those treated open
      (p<0.001). Laparoscopic approach was associated with increased patient travel and
      treatment delay, but to a lesser extent than the robotic approach (p<0.001). In
      high-risk patients, treatment delays remained significantly longer for minimally
      invasive approaches (p<0.001). Other factors associated with the robotic approach
      included referral from an outside facility, treatment at an academic or high
      volume hospital, higher income, and private insurance. Potential limitations
      include the retrospective observational design and lack of external validation of
      the primary outcomes. CONCLUSIONS: The robotic approach is associated with
      increased travel burden and treatment delay, potentially limiting access to
      surgical care.

PMID- 27713801
TI  - The association between institution at orchiectomy and outcomes on active
      surveillance for clinical stage I germ cell tumours.
AB  - INTRODUCTION: Institutional experience has been associated with improved outcomes
      for various malignancies, including testicular cancer. The present study
      evaluated whether institution at orchiectomy was associated with outcomes on
      active surveillance (AS) for clinical stage (CS) I germ cell tumours (GCT).
      METHODS: 815 patients with CSI GCT managed with AS at the Princess Margaret
      Cancer Centre were identified. Princess Margaret is a tertiary academic
      institution with a multidisciplinary testicular cancer clinic involving radiation
      oncologists, medical oncologists, and urologists, and has research experience in
      testicular cancer care. The association between institution of orchiectomy
      (Princess Margaret vs. Other) and time to progression on AS was analyzed using
      multivariable Cox proportional hazards models. Academic vs. non-academic
      institutions were compared in a sensitivity analysis. RESULTS: Patients
      undergoing orchiectomy at Princess Margaret for non-seminoma GCT were
      significantly less likely to have pure embryonal carcinoma (EC) in orchiectomy
      pathology (odds ratio [OR] 0.33; p=0.008) and CSIB disease (OR 0.47; p=0.014).
      Seminoma characteristics did not differ significantly between institution groups.
      In non-seminoma GCT, median followup was 5.4 years, 27% progressed on AS, and
      institution of orchiectomy was not associated with time to progression in either
      univariate (hazard ratio [HR] 0.79; p=0.33) or multivariable analyses (HR 1.01;
      p=0.97). In seminoma, median followup was 4.7 years, 12% progressed on AS, and
      institution of orchiectomy was not associated with progression (univariate: HR
      0.87; p=0.73; multivariable: HR 0.98; p=0.96). Sensitivity analyses demonstrated
      similar results. CONCLUSIONS: Among CSI GCT patients managed on AS at a
      specialized cancer centre, there appears to be no difference in oncologic
      outcomes based upon the institution where orchiectomy was performed.

PMID- 27713803
TI  - Pursuing clinician investigator programs in residency.

PMID- 27713802
TI  - The role of voiding cystourethrography in the investigation of children with
      urinary tract infections.
AB  - Urinary tract infections (UTIs) represent a common bacterial cause of febrile
      illness in children. Of children presenting with a febrile UTI, 25-40% are found
      to have vesicoureteral reflux (VUR). Historically, the concern regarding VUR was
      that it could lead to recurrent pyelonephritis, renal scarring, hypertension, and
      chronic kidney disease. As a result, many children underwent invasive surgical
      procedures to correct VUR. We now know that many cases of VUR are low-grade and
      have a high rate of spontaneous resolution. The roles of surveillance, antibiotic
      prophylaxis, endoscopic injection, and ureteral reimplantation surgery also
      continue to evolve. In turn, these factors have influenced the investigation of
      febrile UTIs. Voiding cystourethrography (VCUG) is the radiographic test of
      choice to diagnose VUR. Due to its invasive nature and questionable benefit in
      many cases, the American Academy of Pediatrics (AAP) no longer recommends VCUG
      routinely after an initial febrile UTI. Nevertheless, these guidelines pre-date
      the landmark Randomized Intervention of Children with Vesicoureteral Reflux
      (RIVUR) trial and there continues to be controversy regarding the diagnosis and
      management of VUR. This paper discusses the current literature regarding
      radiographic testing in children with febrile UTIs and presents a practical risk
      based approach for deciding when to obtain a VCUG.

PMID- 27713804
TI  - Cognitive Enhancement Therapy Improves Resting-State Functional Connectivity in
      Early Course Schizophrenia.
AB  - OBJECTIVE: Cognitive remediation is emerging as an effective psychosocial
      intervention for addressing untreated cognitive and functional impairments in
      persons with schizophrenia, and might achieve its benefits through neuroplastic
      changes in brain connectivity. This study seeks to examine the effects of
      cognitive enhancement therapy (CET) on fronto-temporal brain connectivity in a
      randomized controlled trial with individuals in the early course of
      schizophrenia. METHOD: Stabilized, early course outpatients with schizophrenia or
      schizoaffective disorder (N = 41) were randomly assigned to CET (n = 25) or an
      active enriched supportive therapy (EST) control (n = 16) and treated for 2
      years. Functional MRI data were collected annually, and pseudo resting-state
      functional connectivity analysis was used to examine differential changes in
      fronto-temporal connectivity between those treated with CET compared with EST.
      RESULTS: Individuals receiving CET evidenced significantly less functional
      connectivity loss between the resting-state network and the left dorsolateral
      prefrontal cortex as well as significantly increased connectivity with the right
      insular cortex compared to EST (all corrected p < .01). These neural networks are
      involved in emotion processing and problem-solving. Increased connectivity with
      the right insula significantly mediated CET effects on improved emotion
      perception (z' = -1.96, p = .021), and increased connectivity with the left
      dorsolateral prefrontal cortex mediated CET-related improvements in emotion
      regulation (z' = -1.71, p = .052). CONCLUSIONS: These findings provide
      preliminary evidence that CET, a psychosocial cognitive remediation intervention,
      may enhance connectivity between frontal and temporal brain regions implicated in
      problem-solving and emotion processing in service of cognitive enhancement in
      schizophrenia.

PMID- 27713805
TI  - Vitamin D Supplementation and High-Density Lipoprotein Cholesterol: A Study in
      Healthy School Children.
AB  - BACKGROUND: The high-density lipoprotein cholesterol (HDL-C) level has been shown
      to have a significant role in the prevention of cardiovascular diseases and
      atherosclerosis. Low vitamin D levels have been shown to be correlated with
      dyslipidemia, but limited data exist on indigenous children. OBJECTIVES: We aimed
      to investigate the effect of vitamin D supplementation on HDL-C levels in school
      aged Iranian children. METHODS: In this prospective controlled clinical trial, 47
      healthy children (23 boys) aged 10 - 14 years, students of Birjand (Iran)
      elementary schools, were selected and randomly divided into two groups. The study
      group received a vitamin D supplement (1000 mg capsule) daily for one month, and
      placebo tablets were prescribed to the controls. Before and after the treatment
      course, the serum HDL-C and 25-hydroxy vitamin D levels of both groups were
      measured. The data were analyzed by SPSS, ver. 16, and Chi-square tests, Fisher's
      exact test, paired-sample t-tests, and Pearson's correlation were used, wherever
      appropriate. The significance level was set at P < 0.05. RESULTS: Forty children
      completed the study; their mean age was 11.5 +/- 1.175 years. The mean serum
      levels of both HDL-C and vitamin D showed a significant rise following the
      treatment in the study group (P = 0.007 and P < 0.001, respectively), whereas
      both variables decreased slightly in the control group (P = 0.27). There was no
      statistically significant difference in the mean serum levels of HDL-C and
      vitamin D between the two groups after the intervention (P = 0.11 and P = 0.20,
      respectively). CONCLUSIONS: Vitamin D supplements seem to have a positive impact
      on serum HDL-C levels and may be effective in reducing the risk of cardiovascular
      diseases in the long term.

PMID- 27713807
TI  - The Diagnostic Significance of Comorbidities of Congenital Heart Diseases, Low
      Set Ears, and Intrauterine Growth Restriction in Neonates With Trisomies 13 and
      18.
AB  - BACKGROUND: Trisomies 13 and 18 (T13/18) are autosomal trisomy syndromes with
      dismal prognoses. Deciding whether to perform a chromosomal analysis for the
      definitive diagnosis is often difficult (even for experienced pediatricians)
      because representative clinical signs may not be found in all T13/18 neonates.
      OBJECTIVES: This study aimed to investigate any clinical signs that could be
      useful for screening for T13/18 in participants without the representative
      clinical signs traditionally found in odd-looking neonates with malformation
      syndromes. PATIENTS AND METHODS: We retrospectively analyzed 15 T13/18 patients,
      33 trisomy 21 patients, and 48 controls with other malformation syndromes, for
      apparent clinical signs during the neonatal period. All participants had been
      admitted to the neonatal intensive care unit of Kansai Medical University over a
      nine-year period. RESULTS: The three leading clinical signs in patients with
      T13/18 were congenital heart diseases (CHD; 100%), low-set ears (LSE; 80%), and
      intrauterine growth restriction (IUGR; 73.3%). A comorbidity of these two leading
      non-specific clinical signs was CHD with LSE, which showed the highest diagnostic
      accuracy between T13/18 and controls with a sensitivity of 80.0% and a negative
      predictive value of 92.5%. The chi-square test among these three groups (P <
      0.01) and multiple comparison tests of proportional differences showed that the
      comorbidity of CHD with LSE was specific for autosomal trisomy syndromes. A
      comorbidity of CHD with IUGR also revealed a similar diagnostic accuracy with a
      sensitivity of 73.3% and a negative predictive value of 90.9% as well as a
      specificity for T13/18. CONCLUSIONS: The comorbidities of either CHD with LSE or
      CHD with IUGR should be suspected in neonates with autosomal trisomy syndromes,
      particularly T13/18 without the expected representative clinical signs.

PMID- 27713806
TI  - Obese Chinese Primary-School Students and Low Self-Esteem: A Cross-Sectional
      Study.
AB  - OBJECTIVES: The aim of this study was to examine several factors related to low
      self-esteem among obese Chinese primary-school students. METHODS: A cross
      sectional study was conducted between June 2009 and June 2010. A total of 1,410
      primary-school students (China grades 4 - 6) in Changsha city were divided into
      normal weight (n = 1,084), overweight (n = 211), and obese groups (n = 115)
      according to world health organization (WHO) growth standards for body mass index
      (BMI). The students were assessed using the self-esteem scale (SES) and a general
      situation questionnaire. Caregivers completed questionnaires about their child's
      weight status. Self-esteem levels were explored; any factors related to low self
      esteem were analyzed using logistic regression analysis. RESULTS: The average
      self-esteem score among overweight or obese primary-school students was found to
      be lower than that of normal-weight students. The proportion of students with low
      self-esteem in the obese group was more than that in the normal-weight and
      overweight groups. Multiple logistic regression analysis showed that obesity
      status (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.25 - 6.22),
      overweight status (OR, 2.60; 95% CI, 1.71 - 3.95), obesity considered by
      children's grandparents (OR, 1.76; 95% CI, 1.05 - 2.96), dissatisfaction with
      height (OR, 1.55; 95% CI, 1.11 - 2.18), and dissatisfaction with weight (OR,
      1.45; 95% CI, 1.05 - 2.01) were the risk factors for low self-esteem for primary
      school students, while satisfaction with academic performance was a protective
      factor (OR, 0.22; 95% CI, 0.07 - 0.71). CONCLUSIONS: For Chinese primary-school
      students, low self-esteem is associated with higher weight status and self
      perceived body shape and academic performance. In addition, grandparental opinion
      of a child's weight also contributes to low self-esteem.

PMID- 27713808
TI  - Depressor Anguli Oris in IVF Twins.

PMID- 27713809
TI  - Comparison of Oral Acetaminophen Versus Ibuprofen in Premature Infants With
      Patent Ductus Arteriosus.
AB  - BACKGROUND: Patent ductus arteriosus (PDA) is a common cause of morbidity. The
      aim of this study was to compare the efficacy of oral Acetaminophen and oral
      Ibuprofen for the closure of patent ductus arteriosus (PDA) in preterm infants.
      OBJECTIVES: This study demonstrated that, there was no significant difference
      between treatment of PDA with either oral Acetaminophen or oral Ibuprofen in
      preterm neonates. PATIENTS AND METHODS: This clinical trial, randomized study,
      enrolled 120 infants, with a gestational age of < 37 weeks, who were admitted in
      neonatal intensive care unit of Afzalipour hospital, Kerman, Iran, in 2014. PDA
      was confirmed echocardiographically. The trial was registered in Iranian registry
      of clinical trials (Reg. No. 25542). Sixty-seven infants received oral
      Acetaminophen (15mg/kg every six hours for three days) and 62 infants received
      Ibuprofen (an initial dose of 20 mg/kg, followed by 10 mg/kg at 24 and 48 hours).
      To evaluate the efficacy of the treatment, a second echocardiography was done
      after completing the treatment. RESULTS: After the first course of the treatment,
      PDA closed in 55 (82.1 %) patients who received oral Acetaminophen vs. 47 (75.8
      %) of those given oral Ibuprofen (P = 0.38). After the second course of
      treatment, PDA closed in 50 % of oral Acetaminophen group and 73.3% of oral
      Ibuprofen group (P = 0.21). CONCLUSIONS: This study demonstrated that, there was
      no significant difference between treatment of PDA with either oral Acetaminophen
      or oral Ibuprofen in preterm neonates. Oral Ibuprofen can effectively close PDA
      but is unfortunately associated with some adverse effects limiting its utility
      thus we studied an alternative drug with similar efficacy and less adverse
      effects. This study has recommends Acetaminophen with minimal complications for
      the treatment of PDA in preterm neonates instead of Ibuprofen.

PMID- 27713810
TI  - The Clinical Course of Patients With Atrial Septal Defects.
AB  - BACKGROUND: Atrial septal defect (ASD) is a common congenital heart disease.
      OBJECTIVES: The aim of this study was to assess the clinical course of ASD, as
      well as its frequency of spontaneous closure and regression of diameter. METHODS:
      In a study conducted from 2000 to 2011, 192 consecutive patients with an isolated
      ASD were followed up regularly with periodic echocardiographic evaluations
      according to a standardized protocol. The study was conducted in two series of
      patients: infants and children and adults. Infants were classified into three
      groups based on ASD diameter: small (<= 5 mm), medium (6 - 9 mm), and large (> 9
      mm). In the same manner, the ASD size in children and adults was categorized into
      three groups: small (<= 10), medium (10 - 20 mm), and large (> 20 mm). RESULTS:
      The patients consisted of 76 (39.6%) males and 116 (60.4%) females. The mean age
      of patients at diagnosis was 16.12 +/- 15.66 years (range 1 week - 75 years). The
      mean follow-up duration was 70 +/- 9 months (range: 25 - 119 months). The most
      prevalent age group was adult patients (> 20 years), and most ASDs were of medium
      size (1 - 2 cm). The most common complication was mild pulmonary hypertension (31
      cases, 16.2%), and Eisenmenger phenomenon was the rarest complication (2 cases,
      1%). Overall spontaneous closure of ASD occurred in 42 (21.9%) cases. Spontaneous
      closure in cases with small defects occurred in 18 of 22 (81%) infants and 24 of
      81 children > 1 years of age. Regression of ASD size occurred in 2 (9.5%) infants
      and 3 (3.7%) children. No spontaneous closure was observed in cases with a defect
      size > 10 mm, and no spontaneous occlusion was detected in adolescents or adults.
      Seventy-two percent (n = 139) of patients needed surgical repair or transcatheter
      closure of the ASD. CONCLUSIONS: It is concluded that atrial septal defects < 6
      mm typically close spontaneously, and ASDs measuring 6 - 9 mm may regress in
      infants and children. An ASD > 1 cm has little chance of spontaneous closure and
      may need surgical or device closure. ASD diameter and age at diagnosis are the
      most important predictors of spontaneous closure and the need for possible
      surgical or device closure.

PMID- 27713811
TI  - High-Normal Arterial Blood Pressure in Children With Excess Body Weight.
AB  - BACKGROUND: Childhood overweight and obesity are common causes of metabolic
      disorders that persist until adulthood. OBJECTIVES: The purpose of this study was
      to determine the prevalence of high-normal arterial blood pressure (ABP) in
      children with excess body weight. MATERIAL AND METHODS: A total of 1,093
      schoolchildren aged 10 - 12 years (51% girls and 49% boys) participated in the
      study. The children's weight, height, body fat percentage (BFP), waist and hip
      circumference, and ABP were measured. The waist-to-height ratio (WHtR) and body
      mass index (BMI) were calculated and compared to the normative reference values
      accepted by the International obesity task force (IOTF). RESULTS: Excess weight
      was identified in 20% of the participants, and obesity in 5%. A total of 35.5% of
      overweight children had above-normal ABP, which implied hypertension. In obese
      children, that proportion equaled 59.3%. BFP was 6.5% greater in children with
      hypertension than in those with normal BP. The children with hypertension also
      had a 7.6-cm larger waist circumference, a 7.6-cm larger hip circumference, and a
      greater WHtR (by 0.04). CONCLUSIONS: Excess body weight was identified in 25% of
      children aged 10 - 12 years, significantly increasing their risk of developing
      hypertension.

PMID- 27713812
TI  - Relationship Between the Presence of Eczema Herpeticum and the Significance of
      Clinical and Laboratory Tests in Korean Children With Atopic Dermatitis.
AB  - BACKGROUND: Eczema herpeticum (EH) is a herpes simplex virus (HSV) infection
      superimposed on atopic dermatitis (AD). OBJECTIVES: The aim of this study was to
      evaluate the relationship between clinical features and laboratory tests,
      including skin cultures, total IgE, eosinophil count, eosinophil cationic
      protein, and 25-hydroxyvitamin D3 (25-(OH)D3), in Korean children with AD
      according to the presence of EH. PATIENTS AND METHODS: We enrolled 380 patients
      aged 6 months to 18 years who were admitted to Busan St. Mary's hospital from
      January 2012 to December 2014. All 380 subjects were divided into two groups: the
      control and the AD group. The AD group was further divided into two subgroups:
      EH+ and EH-. RESULTS: The male gender was related to the presence of EH (odds
      ratio of 2.56; 95% confidence interval, 1.19 - 5.53, P = 0.01), but age and 25
      (OH)D3 levels were not. After adjusting for age, gender, and 25-(OH)D3, no
      significant relationship was found between total IgE, eosinophil cationic protein
      or eosinophil count levels and the presence of EH. The relationship between
      positive skin cultures and the presence of EH was significant (P < 0.001) and the
      presence of methicillin-resistant Staphylococcus aureus (MRSA) was also related
      to the development of EH (OR, 0.19; 95% CI, 0.04 - 0.92, P = 0.03). CONCLUSIONS:
      We conclude that while male gender, positive skin culture results, and the
      presence of MRSA are factors influencing EH, serum 25-(OH)D3 levels are not
      associated with EH in Korean AD children.

PMID- 27713813
TI  - Insulin Edema in Type 1 Diabetes Mellitus: Report of a Case and Brief Review of
      the Literature.

PMID- 27713814
TI  - Helicobacter pylori Antibiotic Resistance: What is the Future of Treatment?

PMID- 27713815
TI  - Altered functional organization within the insular cortex in adult males with
      high-functioning autism spectrum disorder: evidence from connectivity-based
      parcellation.
AB  - BACKGROUND: The insular cortex comprises multiple functionally differentiated sub
      regions, each of which has different patterns of connectivity with other brain
      regions. Such diverse connectivity patterns are thought to underlie a wide range
      of insular functions, including cognitive, affective, and sensorimotor
      processing, many of which are abnormal in autism spectrum disorder (ASD).
      Although past neuroimaging studies of ASD have shown structural and functional
      abnormalities in the insula, possible alterations in the sub-regional
      organization of the insula and the functional characteristics of each sub-region
      have not been examined in the ASD brain. METHODS: Resting-state functional
      magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with
      ASD and 38 matched typically developed (TD) controls. A data-driven clustering
      analysis was applied to rs-fMRI data of voxels in the left and right insula to
      automatically group voxels with similar intrinsic connectivity pattern into a
      cluster. After determining the optimal number of clusters based on information
      theoretic measures of variation of information and mutual information, functional
      parcellation patterns in both the left and the right insula were compared between
      the TD and ASD groups. Furthermore, functional profiles of each sub-region were
      meta-analytically decoded using Neurosynth and were compared between the groups.
      RESULTS: We observed notable alterations in the anterior sector of the left
      insula and the middle ventral sub-region of the right insula in the ASD brain.
      Meta-analytic decoding revealed that whereas the anterior sector of the left
      insula contained two functionally differentiated sub-regions for cognitive,
      sensorimotor, and emotional/affective functions in TD brain, only a single
      functional cluster for cognitive and sensorimotor functions was identified in the
      anterior sector in the ASD brain. In the right insula, the middle ventral sub
      region, which is primarily specialized for sensory- and auditory-related
      functions, showed a significant volumetric increase in the ASD brain compared
      with the TD brain. CONCLUSIONS: The results indicate an altered organization of
      sub-regions in specific parts of the left and right insula of the ASD brain. The
      alterations in the left and right insula may constitute neural substrates
      underlying abnormalities in emotional/affective and sensory functions in ASD.

PMID- 27713816
TI  - CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and
      stem cell-derived neurons.
AB  - BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability
      and autism, results from the expansion of a CGG-repeat tract in the 5'
      untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles,
      known as full mutation (FM) alleles, are epigenetically silenced in
      differentiated cells thus resulting in the loss of FMRP, a protein important for
      learning and memory. The timing of repeat expansion and FMR1 gene silencing is
      controversial. METHODS: We monitored the repeat size and methylation status of
      FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent
      stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended
      period of time either as stem cells or differentiated into neurons. We used a PCR
      assay optimized for the amplification of large CGG repeats for sizing, and a
      quantitative methylation-specific PCR for the analysis of FMR1 promoter
      methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were
      determined by western blotting and immunofluorescence. Chromatin
      immunoprecipitation was used to study the association of repressive histone marks
      with the FMR1 gene in FXS ESCs. RESULTS: We show here that while FMR1 gene
      silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles
      contract and when the repeat number drops below ~400, DNA methylation erodes,
      even when the repeat number remains >200. The resultant active alleles do not
      show the large step-wise expansions seen in stem cells from other repeat
      expansion diseases. Furthermore, there may be selection against large active
      alleles and these alleles do not expand further or become silenced on neuronal
      differentiation. CONCLUSIONS: Our data support the hypotheses that (i) large
      expansions occur prezygotically or in the very early embryo, (ii) large
      unmethylated alleles may be deleterious in stem cells, (iii) methylation can
      occur on alleles with >400 repeats very early in embryogenesis, and (iv)
      expansion and contraction may occur by different mechanisms. Our data also
      suggest that the threshold for stable methylation of FM alleles may be higher
      than previously thought. A higher threshold might explain why some carriers of FM
      alleles escape methylation. It may also provide a simple explanation for why
      silencing has not been observed in mouse models with >200 repeats.

PMID- 27713818
TI  - Awareness of radiographic guidelines for low back pain: a survey of Australian
      chiropractors.
AB  - BACKGROUND: Chiropractors have been shown to refer for lumbar radiography in
      clinical scenarios inconsistent with the current clinical guidelines for low back
      pain. It is unknown whether this is due to lack of adherence with known
      guidelines or a lack of awareness of relevant guidelines. Therefore, the aim of
      this study is to determine Australian chiropractors' awareness of, and reported
      adherence to, radiographic guidelines for low back pain. Demographic,
      chiropractic practice and radiographic usage characteristics will be investigated
      for association with poor guideline adherence. METHODS: An online survey was
      distributed to Australian chiropractors from July to September, 2014. Survey
      questions assessed demographic, chiropractic practice and radiographic usage
      characteristics, awareness of radiographic guidelines for low back pain and the
      level of agreement with current guidelines. Results were analysed with
      descriptive statistics and logistic regression analysis. RESULTS: There were 480
      surveys completed online. Only 49.6 % (95 % confidence interval (95 % CI): 44.9,
      54.4) reported awareness of radiographic guidelines for low back pain.
      Chiropractors reported a likelihood of referring for radiographs for low back
      pain: in new patients (47.6 % (95 % CI: 42.9, 52.3)); to confirm biomechanical
      pathologies (69.0 % (95 % CI: 64.5, 73.1)); to perform biomechanical analysis
      (37.5 % (95 % CI: 33.1, 42.0)); or to screen for contraindications (39.4 % (95 %
      CI: 35.0, 44.0)). Chiropractors agreed that radiographs for low back pain could
      be useful for: acute low back pain (54.0 % (95 % CI: 49.2, 58.7)); screening for
      contraindications (55.8 % (95 % CI: 51.0, 60.5)); or to confirm diagnosis and
      direct treatment (61.3 % (95 % CI: 56.5, 65.9)). Poorer adherence to current
      guidelines was seen if the chiropractor referred to in-house radiographic
      facilities, practiced a technique other than diversified technique or was unaware
      or unsure of current radiographic guidelines for low back pain. CONCLUSION: Only
      50 % of Australian chiropractors report awareness of current radiographic
      guidelines for low back pain. A poorer awareness of guidelines is associated with
      an increase in the reported likelihood of use, and the perceived usefulness of
      radiographs for low back pain, in clinical situations that fall outside of
      current guidelines. Therefore, education strategies may help to increase
      guideline knowledge and compliance.

PMID- 27713817
TI  - VAChT overexpression increases acetylcholine at the synaptic cleft and
      accelerates aging of neuromuscular junctions.
AB  - BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of
      diseases, including amyotrophic lateral sclerosis (ALS). However, it remains
      unknown whether changes in cholinergic transmission contributes to age- and
      disease-related degeneration of the motor system. Here we investigated the effect
      of moderately increasing levels of synaptic acetylcholine (ACh) on the
      neuromuscular junction (NMJ), muscle fibers, and motor neurons during development
      and aging and in a mouse model for amyotrophic lateral sclerosis (ALS). METHODS:
      Chat-ChR2-EYFP (VAChTHyp) mice containing multiple copies of the vesicular
      acetylcholine transporter (VAChT), mutant superoxide dismutase 1 (SOD1G93A), and
      Chat-IRES-Cre and tdTomato transgenic mice were used in this study. NMJs, muscle
      fibers, and alpha-motor neurons' somata and their axons were examined using a
      light microscope. Transcripts for select genes in muscles and spinal cords were
      assessed using real-time quantitative PCR. Motor function tests were carried out
      using an inverted wire mesh and a rotarod. Electrophysiological recordings were
      collected to examine miniature endplate potentials (MEPP) in muscles. RESULTS: We
      show that VAChT is elevated in the spinal cord and at NMJs of VAChTHyp mice. We
      also show that the amplitude of MEPPs is significantly higher in VAChTHyp
      muscles, indicating that more ACh is loaded into synaptic vesicles and released
      into the synaptic cleft at NMJs of VAChTHyp mice compared to control mice. While
      the development of NMJs was not affected in VAChTHyp mice, NMJs prematurely
      acquired age-related structural alterations in adult VAChTHyp mice. These
      structural changes at NMJs were accompanied by motor deficits in VAChTHyp mice.
      However, cellular features of muscle fibers and levels of molecules with critical
      functions at the NMJ and in muscle fibers were largely unchanged in VAChTHyp
      mice. In the SOD1G93A mouse model for ALS, increasing synaptic ACh accelerated
      degeneration of NMJs caused motor deficits and resulted in premature death
      specifically in male mice. CONCLUSIONS: The data presented in this manuscript
      demonstrate that increasing levels of ACh at the synaptic cleft promote
      degeneration of adult NMJs, contributing to age- and disease-related motor
      deficits. We thus propose that maintaining normal cholinergic signaling in
      muscles will slow degeneration of NMJs and attenuate loss of motor function
      caused by aging and neuromuscular diseases.

PMID- 27713820
TI  - Fibromyalgia syndrome: metabolic and autophagic processes in intermittent cold
      stress mice.
AB  - Fibromyalgia is characterized by widespread musculoskeletal pain, fatigue, and
      depression. The aim was to analyze potential mitochondrial dysfunction or
      autophagy in mice after exposure to intermittent cold stress (ICS). Muscle and
      liver specimens were obtained from 36 mice. Lactate dehydrogenase (LDH) activity
      was measured. Microtubule-associated protein light chain 3 (MAP1LC3B) and
      glycogen content were determined histologically; muscle ultrastructure by
      electron microscopy. Mitochondrial- and autophagy-related markers were analyzed
      by RT-qPCR and Western blotting. ATP level, cytotoxicity, and caspase 3 activity
      were measured in murine C2C12 myoblasts after ICS exposure. Coenzyme Q10B
      (COQ10B) transcript was up-regulated in limb muscle of ICS mice, whereas its
      protein content was stable. Cytochrome C oxidase 4 (COX4I1) and LDH activity
      increased in limb muscle of male ICS mice. Glycogen content was lower in muscle
      and liver tissue of male ICS mice. Electron micrographs of ICS mice specimens
      showed mitochondrial damage and autophagic vesicles. A significant up-regulation
      of autophagic transcripts of MAP1LC3B and BECLIN 1 (BECN1) was observed. Map1lc3b
      protein showed an aggregated distribution in ICS mice and SqSTM1/p62 (p62)
      protein level was stable. Furthermore, ATP level and caspase activity, detected
      as apoptotic marker, were significantly lowered after ICS exposure in
      differentiated C2C12 myoblasts. The present study shows that ICS mice are
      characterized by mitochondrial dysfunction, autophagic processes, and metabolic
      alterations. Further investigations could dissect autophagy process in the
      proposed model and link these mechanisms to potential therapeutic options for
      fibromyalgia.

PMID- 27713821
TI  - RGS14 regulates the lifetime of Galpha-GTP signaling but does not prolong
      Gbetagamma signaling following receptor activation in live cells.
AB  - RGS14 is a multifunctional scaffolding protein possessing two distinct G protein
      interaction sites including a regulator of G protein signaling (RGS) domain that
      acts as a GTPase activating protein (GAP) to deactivate Galphai/o-GTP proteins,
      and a G protein regulatory (GPR) motif that binds inactive Galphai1/3-GDP
      proteins independent of Gbetagamma. GPR interactions with Galphai recruit RGS14
      to the plasma membrane to interact with Galphai-linked GPCRs and regulate Galphai
      signaling. While RGS14 actions on Galpha proteins are well characterized,
      consequent effects on Gbetagamma signaling remain unknown. Conventional RGS
      proteins act as dedicated GAPs to deactivate Galpha and Gbetagamma signaling
      following receptor activation. RGS14 may do the same or, alternatively, may
      coordinate its actions to deactivate Galpha-GTP with the RGS domain and then
      capture the same Galpha-GDP via its GPR motif to prevent heterotrimer
      reassociation and prolong Gbetagamma signaling. To test this idea, we compared
      the regulation of G protein activation and deactivation kinetics by a
      conventional RGS protein, RGS4, and RGS14 in response to GPCR agonist/antagonist
      treatment utilizing bioluminescence resonance energy transfer (BRET). Co
      expression of either RGS4 or RGS14 inhibited the release of free Gbetagamma after
      agonist stimulation and increased the deactivation rate of Galpha, consistent
      with their roles as GTPase activating proteins (GAPs). Overexpression of inactive
      Galphai1 to recruit RGS14 to the plasma membrane did not alter RGS14's capacity
      to act as a GAP for a second Galphao protein. These results demonstrate the role
      of RGS14 as a dedicated GAP and suggest that the G protein regulatory (GPR) motif
      functions independently of the RGS domain and is silent in regulating GAP
      activity in a cellular context.

PMID- 27713822
TI  - Population pharmacokinetic and pharmacodynamic analyses of safinamide in subjects
      with Parkinson's disease.
AB  - Safinamide is an orally administered alpha-aminoamide derivative with both
      dopaminergic and non-dopaminergic properties. Nonlinear mixed effects models for
      population pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PKPD)
      analyses were developed using records from, respectively, 623 and 668 patients
      belonging to two Phase 3, randomized, placebo-controlled, double-blind efficacy
      studies. The aim was to estimate safinamide population PK parameters in patients
      with Parkinson's disease (PD) on stable levodopa therapy, and to develop a model
      of safinamide effect on the PD phase of normal functioning (ON-time). The final
      models were internally evaluated using visual predictive checks (VPCs),
      prediction corrected-VPC, and nonparametric bootstrap analysis. Safinamide
      profiles were adequately described by a linear one-compartmental model with first
      order absorption and elimination. CL/F, Vd/F, and KA (95% confidence interval
      [CI]) were 4.96 (4.73-5.21) L/h, 166 (158-174) L, and 0.582 (0.335-0.829) h-1,
      respectively. CL/F and Vd/F increased with body weight, while age, gender, renal
      function, and exposure to levodopa did not influence safinamide PK. The observed
      ON-time values were adequately described by a linear model, with time in the
      study period as dependent variable, and rate of ON-time change and baseline plus
      offset effect as slope and intercept parameters. Safinamide treatment resulted in
      an increase in ON-time of 0.73 h (week 4), with further ON-time increase with the
      same slope as placebo. The increase was not influenced by age, levodopa, or
      safinamide exposure. The population models adequately describe the population PK
      of safinamide and safinamide effect on ON-time. No dose adjustments in elderly
      and mild to moderate renally impaired patients are requested.

PMID- 27713819
TI  - Attention to emotional stimuli in borderline personality disorder - a review of
      the influence of dissociation, self-reference, and psychotherapeutic
      interventions.
AB  - Interactions between attention and processing of emotional stimuli shed light on
      both sensitivity to emotional stimuli as well as emotion dysregulation. Both of
      the latter processes have been proposed as central characteristics of altered
      emotion processing in those with borderline personality disorder (BPD). This
      review first summarizes the conflicting behavioural, psychophysiological and
      neuroimaging evidence for the hypothesis that emotional dysregulation should be
      reflected by higher distractibility through emotional stimuli in those with BPD.
      Dissociation, self-reference, as well as symptom severity modulated by
      psychotherapeutic interventions are proposed to help clarify divergent findings.
      Data suggest an association of dissociation with impaired task continuation
      during the presentation of interfering emotional and neutral stimuli, as well as
      high recruitment of neuronal attention networks together with a blunted emotional
      response. Considering self-reference, evidence suggests that negative rather than
      positive information may be more self-relevant to those with BPD. This may be due
      to a negative self-concept and self-evaluation. Social or trauma-relevant
      information attracts more attention from individuals with BPD and thus suggests
      higher self-relevance. After psychotherapeutic interventions, initial evidence
      may indicate normalization of the way attention and emotional stimuli interact in
      BPD. When studying attention-emotion interactions in BPD, methodological
      heterogeneities regarding sample, task, and stimulus characteristics need to be
      considered. When doing so, dissociation, self-reference, and psychotherapeutic
      interventions offer promising targets for future studies on attention-emotion
      interactions in those with BPD. This could promote a deeper insight into the
      affected individuals' struggle with emotions.

PMID- 27713823
TI  - Phenotyping and genotyping of CYP2C19 using comparative metabolism of proguanil
      in sickle-cell disease patients and healthy controls in Nigeria.
AB  - Polymorphic expression of metabolic enzymes have been identified as one of the
      key factors responsible for the interindividual/ethnic/racial variability in drug
      metabolism and effect. In Nigeria, there is a disproportionately high incidence
      of sickle-cell disease (SCD), a condition characterized by painful crisis
      frequently triggered by malaria. Proguanil, a substrate of the polymorphic
      CYP2C19, is a chemoprophylactic antimalarial drug widely used among SCD patients
      in Nigeria. This study aimed to conduct a comparative CYP2C19 phenotyping among
      SCD patients and healthy controls and to compare the results with those
      previously reported. One hundred seventy-seven unrelated subjects comprising 131
      SCD patients and 46 non-SCD volunteers were phenotyped. This was carried out by
      collecting pooled urine samples over 8 h following PG administration. Proguanil
      and its major CYP2C19-dependent metabolites were measured by high-performance
      liquid chromatography. Metabolic ratios (MRs) were computed and employed in
      classifying subjects into poor or extensive metabolizers. Among SCD group, 130
      (99.2%) were extensive metabolizers (EMs) and 1 (0.8%) was poor metabolizer (PM)
      of PG, while 95.7 and 4.3% non-SCDs were EMs and PMs, respectively. MRs ranged
      from 0.02 to 8.70 for SCD EMs and from 0.22 to 8.33 for non-SCD EMs . Two non
      SCDs with MRs of 18.18 and 25.76 and the SCD with MR of 16.77 regarded as PMs had
      earlier been genotyped as CYP2C19*2/*2. Poor metabolizers of proguanil in SCD
      patients are reported for the first time. Regardless of clinical significance, a
      difference in metabolic disposition of proguanil and CYP2C19 by SCDs and non-SCDs
      was established.

PMID- 27713825
TI  - Frequency and trends of disease-modifying antirheumatic drug (DMARD) use in
      Germany.
AB  - The aim of this study was to analyze the population-based frequency of classic (c
      ) and biologic (b-) disease-modifying antirheumatic drug (DMARD) use over time,
      selected underlying indications and the specialty of the prescribing physicians
      in Germany. Based on the claims data of the German Pharmacoepidemiological
      Research Database (GePaRD), yearly cross-sectional studies were conducted from
      2004 to 2011. The prevalence of DMARD use was calculated as the number of persons
      with at least one dispensation per 1000 persons stratified by sex and age. In
      2011, we also obtained the proportion of c- and b-DMARDs users with diagnoses of
      selected indications and the proportion of dispensations by specialty of the
      physician. Between 2004 and 2011, the annual prevalence of b-DMARD and c-DMARD
      use increased from 0.350/00 to 1.540/00 and from 6.530/00 to 8.930/00,
      respectively. In 2011, the study population comprised 12.8 million insurants with
      a mean age of 44.0 years. During this year, among c-DMARDs, methotrexate was
      prescribed most frequently (4.760/00), followed by azathioprine (1.720/00) and
      sulfasalazine (1.200/00). For b-DMARDs, adalimumab (0.570/00), etanercept
      (0.460/00), and rituximab (0.230/00) were most frequently used. Notably, b-DMARD
      users more often had a diagnosis of ankylosing spondylitis and psoriasis compared
      to c-DMARD-users (20.7% vs. 2.9% and 20.0% vs. 11.4%, respectively) and b-DMARDs
      were more frequently prescribed by rheumatologists and other specialists. Our
      population-based study highlights the increasing use of c- and b-DMARDs in
      Germany. Compared to c-DMARDs, b-DMARDs were commonly used for indications
      besides rheumatoid arthritis. Future research should therefore also focus on
      their prescription patterns and safety aspects in indications other than RA.

PMID- 27713824
TI  - Comparison of [11C]TZ1964B and [18F]MNI659 for PET imaging brain PDE10A in
      nonhuman primates.
AB  - Phosphodiesterase 10A (PDE10A) inhibitors show therapeutic effects for diseases
      with striatal pathology. PET radiotracers have been developed to quantify in vivo
      PDE10A levels and target engagement for therapeutic interventions. The aim of
      this study was to compare two potent and selective PDE10A radiotracers,
      [11C]TZ1964B and [18F]MNI659 in the nonhuman primate (NHP) brain. Double scans in
      the same cynomolgus monkey on the same day were performed after injection of
      [11C]TZ1964B and [18F]MNI659. Specific uptake was determined in two ways:
      nondisplaceable binding potential (BPND) was calculated using cerebellum as the
      reference region and the PDE-10A enriched striatum as the target region of
      interest (ROI); the area under the time-activity curve (AUC) for the striatum to
      cerebellum ratio was also calculated. High-performance liquid chromatography
      (HPLC) analysis of solvent-extracted NHP plasma identified the percentage of
      intact tracer versus radiolabeled metabolites samples post injection of each
      radiotracer. Both radiotracers showed high specific accumulation in NHP striatum.
      [11C]TZ1964B has higher striatal retention and lower specific striatal uptake
      than [18F]MNI659. The BPND estimates of [11C]TZ1964B were 3.72 by Logan Reference
      model (LoganREF) and 4.39 by simplified reference tissue model (SRTM); the BPND
      estimates for [18F]MNI659 were 5.08 (LoganREF) and 5.33 (SRTM). AUC ratios were
      5.87 for [11C]TZ1964B and 7.60 for [18F]MNI659. Based on BPND values in NHP
      striatum, coefficients of variation were ~10% for [11C]TZ1964B and ~30% for
      [18F]MNI659. Moreover, the metabolism study showed the percentage of parent
      compounds were ~70% for [11C]TZ1964B and ~50% for [18F]MNI659 60 min post
      injection. These data indicate that either [11C]TZ1964B or [18F]MNI659 could
      serve as suitable PDE10A PET radiotracers with distinguishing features for
      particular clinical application.

PMID- 27713826
TI  - Soluble guanylate cyclase redox state under oxidative stress conditions in
      isolated monkey coronary arteries.
AB  - Coronary artery disease is associated with oxidative stress due to the excessive
      generation of free radicals in the vascular wall. This study investigated the
      impact of tert-butyl hydroperoxide (t-BuOOH), a peroxyl radical generator, on the
      redox state of soluble guanylate cyclase (sGC) in isolated monkey coronary
      arteries. Helically cut strips of endothelium-intact monkey coronary arteries
      treated with the nitric oxide synthase inhibitor NG-nitro-L-arginine (10 MUmol/L)
      were exposed for approximately 60 min to either no drug or t-BuOOH (100 MUmol/L)
      in the presence and absence of alpha-tocopherol (300 MUmol/L). Relaxation and
      cGMP levels in response to the sGC stimulator BAY 41-2272 and the sGC activator
      BAY 60-2770 were assessed by organ chamber technique and enzyme immunoassay,
      respectively. The relaxant response to BAY 41-2272 was significantly impaired by
      the exposure to t-BuOOH, whereas the response to BAY 60-2770 was significantly
      augmented. In addition, vascular cGMP accumulation caused by BAY 41-2272 was
      decreased by the exposure to t-BuOOH, whereas for BAY 60-2770, it was increased.
      These effects of t-BuOOH were abolished by coincubation with alpha-tocopherol.
      Furthermore, correlations were observed between BAY compound-induced relaxant
      magnitudes and cGMP levels. Therefore, it is concluded that increased oxidative
      stress leads to disruption of the sGC redox state in monkey coronary arteries.
      This finding is of great importance for understanding coronary physiology in
      primates.

PMID- 27713827
TI  - Evaluation of a novel PXR-knockout in HepaRGTM cells.
AB  - The nuclear pregnane X receptor (PXR) regulates the expression of genes involved
      in the metabolism, hepatobiliary disposition, and toxicity of drugs and
      endogenous compounds. PXR is a promiscuous nuclear hormone receptor (NHR) with
      significant ligand and DNA-binding crosstalk with the constitutive androstane
      receptor (CAR); hence, defining the precise role of PXR in gene regulation is
      challenging. Here, utilising a novel PXR-knockout (KO) HepaRG cell line, real
      time PCR analysis was conducted to determine PXR involvement for a range of
      inducers. The selective PXR agonist rifampicin, a selective CAR activator, 6-(4
      chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4
      dichlorobenzyl)oxime (CITCO), and dual activators of CAR and PXR including
      phenobarbital (PB) were analyzed. HepaRG control cells (5F clone) were responsive
      to prototypical inducers of CYP2B6 and CYP3A4. No response was observed in the
      PXR-KO cells treated with rifampicin. Induction of CYP3A4 by PB, artemisinin, and
      phenytoin was also much reduced in PXR-KO cells, while the response to CITCO was
      maintained. This finding is in agreement with the abolition of functional PXR
      expression. The apparent EC50 values for PB were in agreement between the cell
      lines; however, CITCO was ~threefold (0.3 MUmol/L vs. 1 MUmol/L) lower in the PXR
      KO cells compared with the 5F cells for CYP2B6 induction. Results presented
      support the application of the novel PXR-KO cells in the definitive assignment of
      PXR-mediated CYP2B6 and CYP3A4 induction. Utilization of such cell lines will
      allow advancement in composing structure activity relationships rather than
      relying predominantly on pharmacological manipulations and provide in-depth
      mechanistic evaluation.

PMID- 27713828
TI  - Efficacy and safety evaluation of claudin-4-targeted antitumor therapy using a
      human and mouse cross-reactive monoclonal antibody.
AB  - Claudin-4 (CLDN-4), a tight-junction protein, is overexpressed in various
      malignant tumors, including gastric, colorectal, pancreatic, and breast cancers.
      However, CLDN-4 is also expressed in normal tissues, including the liver,
      pancreas, kidney, and small intestine. Whether CLDN-4 is an effective and safe
      target for cancer therapy has been unclear owing to the lack of a binder with
      both CLDN-4 specificity and cross-reactivity to human and murine cells. In this
      study, we successfully generated a rat anti-CLDN-4 monoclonal antibody (5D12)
      that was specific to, and cross-reactive with, human and mouse CLDN-4. 5D12
      recognized the second extracellular domain of human CLDN-4 in a conformation
      dependent manner. A human-rat chimeric IgG1 of 5D12 (xi-5D12) activated the
      Fcgamma IIIa receptor, indicating the activation of antibody-dependent cellular
      cytotoxicity in CLDN-4-expressing cells. Moreover, xi-5D12 significantly
      suppressed tumor growth in mice bearing human colorectal and gastric tumors
      without apparent adverse effects, such as weight loss or liver and kidney damage.
      These results suggest that CLDN-4 is a potent target for cancer therapy and that
      an anti-CLDN-4 antibody is a promising candidate anticancer agent.

PMID- 27713829
TI  - Equine hepatocytes: isolation, cryopreservation, and applications to in vitro
      drug metabolism studies.
AB  - Despite reports of the successful isolation of primary equine hepatocytes, there
      are no published data regarding the successful cryopreservation of these isolated
      cells. In this study, a detailed description of the procedures for isolation,
      cryopreservation, and recovery of equine hepatocytes are presented. Furthermore,
      the intrinsic clearance (Clint) and production of metabolites for three drugs
      were compared between freshly isolated and recovered cryopreserved hepatocytes.
      Primary equine hepatocytes were isolated using a two-step collagenase perfusion
      method, with an average cell yield of 2.47 +/- 2.62 * 106 cells/g of perfused
      liver tissue and viability of 84.1 +/- 2.62%. These cells were cryopreserved with
      William's medium E containing 10% fetal bovine serum with 10% DMSO. The viability
      of recovered cells, after a 30% Percoll gradient, was 77 +/- 11% and estimated
      recovery rate was approximately 27%. These purified cells were used to determine
      the in vitro Clint of three drugs used in equine medicine; omeprazole, flunixin,
      and phenylbutazone, via the substrate depletion method. Cryopreserved suspensions
      gave a comparable estimation of Clint compared to fresh cells for these three
      drugs as well as producing the same metabolites. This work paves the way for
      establishing a bank of cryopreserved equine hepatocytes that can be used for
      estimating pharmacokinetic parameters such as the hepatic metabolic in vivo
      clearance of a drug as well as producing horse-specific drug metabolites.

PMID- 27713830
TI  - Fighting falsified medicines with paperwork - a historic review of Danish
      legislation governing distribution of medicines.
AB  - BACKGROUND: Many areas of pharmaceutical legislation in the European Union (EU)
      are harmonised in order to promote the internal market and protect public health.
      Ideally, harmonisation leads to less fragmented regulation and cross-border
      complexities. This study, however, focuses on an increasingly harmonised
      legislative area that is subject to increases in requirements and complexities:
      the distribution of medicines. This study compared Danish legislation governing
      the distribution of medicines before and after Denmark joined the EU in order to
      assess the impact of EU harmonisation, as well as to evaluate whether the drastic
      increases in requirements mandated by the Falsified Medicines Directive of 2011
      correspond to a new approach to governing the pharmaceutical supply chain.
      METHODS: A review was conducted of 115 applicable Danish laws, executive orders
      and guidelines from 1913 to 2014. Legal requirements were organised according to
      the year they were published and the companies they affected. Greater changes in
      legislative requirements were developed through inductive content analysis.
      RESULTS: Early legislation positioned pharmacies as gatekeepers, requiring them
      to identify and stop medicines of substandard quality. Legislation to regulate
      the supply chain was slow to materialise. After Denmark joined the EU, the scope
      of legislation widened to include all actors in the supply chain, and the
      quantity of legislation increased dramatically. Simultaneously, requirements
      became more specific, thereby promoting a formalistic interpretation and focusing
      the attention of companies and authorities on predefined areas with little room
      to implement innovative solutions. Over time, documentation became the focus of
      legislation, requiring companies to provide documentary evidence for their
      compliance with legislation. The Falsified Medicines Directive continues these
      trends by increasing requirements for documentation and promoting a formalistic
      interpretation. CONCLUSION: The legislative approach adopted since Denmark joined
      the EU gives companies and medicine inspectors little room to interpret
      legislation. The Falsified Medicines Directive does not depart from this
      approach. Legislation seems more focused on enforcing similar requirements than
      on benefiting public health. Legislation may benefit from allowing room for local
      interpretation of requirements.

PMID- 27713831
TI  - Potential perils of peri-Pokemon perambulation: the dark reality of augmented
      reality?
AB  - Recently, the layering of augmented reality information on top of smartphone
      applications has created unprecedented user engagement and popularity. One
      augmented reality-based entertainment application, Pokemon Go (Pokemon Company,
      Tokyo, Japan) has become the most rapidly downloaded in history. This technology
      holds tremendous promise to promote ambulatory activity. However, there exists
      the obvious potential for distraction-related morbidity. We report two cases,
      presenting simultaneously to our trauma center, with injuries sustained secondary
      to gameplay with this augmented reality-based application.

PMID- 27713832
TI  - A comparative study of enzyme initiators for crosslinking phenol-functionalized
      hydrogels for cell encapsulation.
AB  - BACKGROUND: Dityrosine crosslinking in proteins is a bioinspired method of
      forming hydrogels. This study compares oxidative enzyme initiators for their
      relative crosslinking efficiency and cytocompatibility using the same phenol
      group and the same material platform. Four common enzyme and enzyme-like
      oxidative initiators were probed for resulting material properties and cell
      viability post-encapsulation. RESULTS: All four initiators can be used to form
      phenol-crosslinked hydrogels, however gelation rates are dependent on enzyme
      type, concentration, and the oxidant. Horseradish peroxidase (HRP) or hematin
      with hydrogen peroxide led to a more rapid poly (vinyl alcohol)-tyramine (PVA
      Tyr) polymerization (10-60 min) because a high oxidant concentration was
      dissolved within the macromer solution at the onset of crosslinking, whereas
      laccase and tyrosinase require oxygen diffusion to crosslink phenol residues and
      therefore took longer to gel (2.5+ hours). The use of hydrogen peroxide as an
      oxidant reduced cell viability immediately post-encapsulation. Laccase- and
      tyrosinase-mediated encapsulation of cells resulted in higher cell viability
      immediately post-encapsulation and significantly higher cell proliferation after
      one week of culture. CONCLUSIONS: Overall this study demonstrates that HRP/H2O2,
      hematin/H2O2, laccase, and tyrosinase can create injectable, in situ phenol
      crosslinked hydrogels, however oxidant type and concentration are critical
      parameters to assess when phenol crosslinking hydrogels for cell-based
      applications.

PMID- 27713833
TI  - Missed opportunity to screen and diagnose PTSD and depression among deploying
      shipboard US military personnel.
AB  - BACKGROUND: Depression and post-traumatic stress disorder (PTSD) are significant
      risks for suicide and other adverse events among US military personnel, but
      prevalence data among ship-assigned personnel at the onset of deployment are
      unknown. AIMS: To determine the prevalence of shipboard personnel who screen
      positive for PTSD and/or major depressive disorder (MDD) at the onset of
      deployment, and also those who reported these diagnoses made by a physician or
      healthcare professional in the year prior to deployment. METHOD: Active-duty ship
      assigned personnel (N = 2078) completed anonymous assessments at the beginning of
      deployment. Depression was measured using the Center for Epidemiologic Studies
      Depression Scale (CES-D; score of >=22), and PTSD was assessed using the PTSD
      Checklist-Civilian Version (PCL-C; both score and symptom criteria were used).
      RESULTS: In total, 7.3% (n = 151 of 2076) screened positive for PTSD and 22% (n =
      461 of 2078) for MDD at deployment onset. Only 6% and 15% of those who screened
      positive for PTSD or MDD, respectively, had been diagnosed by a healthcare
      professional in the past year. CONCLUSIONS: Missed opportunities for mental
      healthcare among screen-positive shipboard personnel reduce the benefits
      associated with early identification and linkage to care. Improved methods of
      mental health screening that promote early recognition and referral to care may
      mitigate psychiatric events in theatre. DECLARATION OF INTEREST: This work was
      performed as part of the official duties of the authors as military service
      members or employees of the US Government. COPYRIGHT AND USAGE: This work was
      prepared by military service members or employees of the US Government as part of
      their official duties. As such, copyright protection is not available for this
      work (Title 17, USC, S105).

PMID- 27713834
TI  - Loss of relational continuity of care in schizophrenia: associations with patient
      satisfaction and quality of care.
AB  - BACKGROUND: Users of mental health service are concerned about changes in
      clinicians providing their care, but little is known about their impact. AIMS: To
      examine associations between changes in staff, and patient satisfaction and
      quality of care. METHOD: A national cross-sectional survey of 3379 people aged 18
      or over treated in secondary care for schizophrenia or schizoaffective disorder.
      RESULTS: Nearly 41.9% reported at least one change in their key worker during the
      previous 12 months and 10.5% reported multiple changes. Those reporting multiple
      changes were less satisfied with their treatment and less likely to report having
      a care plan, knowing how to obtain help when in a crisis or to have had
      recommended physical health assessments. CONCLUSIONS: Frequent changes in staff
      providing care for people with psychosis are associated with poorer quality of
      care. Greater efforts need to be made to protect relational continuity of care
      for such patients. DECLARATION OF INTEREST: M.J.C. was co-chair of the expert
      advisory group on the NICE quality standard on Service User Experience in Adult
      Mental Health. S.J.C. has previously been a member of the Health and Social Care
      Board Northern Ireland Formulary Committee. D.S. received a speaker's fee from
      Janssen Cilag in 2011. He is a topic expert on NICE guideline for psychosis and
      schizophrenia in children and young people and a board member of National
      Collaborating Centre for Mental Health. COPYRIGHT AND USAGE: (c) The Royal
      College of Psychiatrists 2016. This is an open access article distributed under
      the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND)
      license.

PMID- 27713835
TI  - Sequence amplification via cell passaging creates spurious signals of positive
      adaptation in influenza virus H3N2 hemagglutinin.
AB  - Clinical influenza A virus isolates are frequently not sequenced directly.
      Instead, a majority of these isolates (~70% in 2015) are first subjected to
      passaging for amplification, most commonly in non-human cell culture. Here, we
      find that this passaging leaves distinct signals of adaptation, which can
      confound evolutionary analyses of the viral sequences. We find distinct patterns
      of adaptation to Madin-Darby (MDCK) and monkey cell culture absent from
      unpassaged hemagglutinin sequences. These patterns also dominate pooled datasets
      not separated by passaging type, and they increase in proportion to the number of
      passages performed. By contrast, MDCK-SIAT1 passaged sequences seem mostly (but
      not entirely) free of passaging adaptations. Contrary to previous studies, we
      find that using only internal branches of influenza virus phylogenetic trees is
      insufficient to correct for passaging artifacts. These artifacts can only be
      safely avoided by excluding passaged sequences entirely from subsequent analysis.
      We conclude that future influenza virus evolutionary analyses should
      appropriately control for potentially confounding effects of passaging
      adaptations.

PMID- 27713836
TI  - Evolutionary dynamics of Enterococcus faecium reveals complex genomic
      relationships between isolates with independent emergence of vancomycin
      resistance.
AB  - Enterococcus faecium, a major cause of hospital-acquired infections, remains
      problematic because of its propensity to acquire resistance to vancomycin, which
      currently is considered first-line therapy. Here, we assess the evolution and
      resistance acquisition dynamics of E. faecium in a clinical context using a
      series of 132 bloodstream infection isolates from a single hospital. All
      isolates, of which 49 (37 %) were vancomycin-resistant, underwent whole-genome
      sequencing. E. faecium was found to be subject to high rates of recombination
      with little evidence of sequence importation from outside the local E. faecium
      population. Apart from disrupting phylogenetic reconstruction, recombination was
      frequent enough to invalidate MLST typing in the identification of clonal
      expansion and transmission events, suggesting that, where available, whole-genome
      sequencing should be used in tracing the epidemiology of E. faecium nosocomial
      infections and establishing routes of transmission. Several forms of the Tn1549
      like element-vanB gene cluster, which was exclusively responsible for vancomycin
      resistance, appeared and spread within the hospital during the study period.
      Several transposon gains and losses and instances of in situ evolution were
      inferred and, although usually chromosomal, the resistance element was also
      observed on a plasmid background. There was qualitative evidence for clonal
      expansions of both vancomycin-resistant and vancomycin-susceptible E. faecium
      with evidence of hospital-specific subclonal expansion. Our data are consistent
      with continuing evolution of this established hospital pathogen and confirm
      hospital vancomycin-susceptible and vancomycin-resistant E. faecium patient
      transmission events, underlining the need for careful consideration before
      modifying current E. faecium infection control strategies.

PMID- 27713838
TI  - Two-Dimensional Hermite Filters Simplify the Description of High-Order Statistics
      of Natural Images.
AB  - Natural image statistics play a crucial role in shaping biological visual
      systems, understanding their function and design principles, and designing
      effective computer-vision algorithms. High-order statistics are critical for
      conveying local features, but they are challenging to study - largely because
      their number and variety is large. Here, via the use of two-dimensional Hermite
      (TDH) functions, we identify a covert symmetry in high-order statistics of
      natural images that simplifies this task. This emerges from the structure of TDH
      functions, which are an orthogonal set of functions that are organized into a
      hierarchy of ranks. Specifically, we find that the shape (skewness and kurtosis)
      of the distribution of filter coefficients depends only on the projection of the
      function onto a 1-dimensional subspace specific to each rank. The
      characterization of natural image statistics provided by TDH filter coefficients
      reflects both their phase and amplitude structure, and we suggest an intuitive
      interpretation for the special subspace within each rank.

PMID- 27713837
TI  - SimBac: simulation of whole bacterial genomes with homologous recombination.
AB  - Bacteria can exchange genetic material, or acquire genes found in the
      environment. This process, generally known as bacterial recombination, can have a
      strong impact on the evolution and phenotype of bacteria, for example causing the
      spread of antibiotic resistance across clades and species, but can also disrupt
      phylogenetic and transmission inferences. With the increasing affordability of
      whole genome sequencing, the need has emerged for an efficient simulator of
      bacterial evolution to test and compare methods for phylogenetic and population
      genetic inference, and for simulation-based estimation. We present SimBac, a
      whole-genome bacterial evolution simulator that is roughly two orders of
      magnitude faster than previous software and includes a more general model of
      bacterial evolution, allowing both within- and between-species homologous
      recombination. Since methods modelling bacterial recombination generally focus on
      only one of these two modes of recombination, the possibility to simulate both
      allows for a general and fair benchmarking. SimBac is available from
      https://github.com/tbrown91/SimBac and is distributed as open source under the
      terms of the GNU General Public Licence.

PMID- 27713839
TI  - Community Engaged Leadership to Advance Health Equity and Build Healthier
      Communities.
AB  - Health is a human right. Equity in health implies that ideally everyone should
      have a fair opportunity to attain their full health potential and, more
      pragmatically, that no one should be disadvantaged from achieving this potential.
      Addressing the multi-faceted health needs of ethnically and culturally diverse
      individuals in the United States is a complex issue that requires inventive
      strategies to reduce risk factors and buttress protective factors to promote
      greater well-being among individuals, families, and communities. With growing
      diversity concerning various ethnicities and nationalities; and with significant
      changes in the constellation of multiple of risk factors that can influence
      health outcomes, it is imperative that we delineate strategic efforts that
      encourage better access to primary care, focused community-based programs, multi
      disciplinary clinical and translational research methodologies, and health policy
      advocacy initiatives that may improve individuals' longevity and quality of life.

PMID- 27713840
TI  - In silico identification of T-type calcium channel blockers: A ligand-based
      pharmacophore mapping approach.
AB  - Limited progress has been made in the quest to identify both selective and non
      toxic T-type calcium channel blocking compounds. The present research work was
      directed toward slaking the same by identifying the selective three dimensional
      (3D) pharmacophore map for T-type calcium channel blockers (CCBs). Using HipHop
      module in the CATALYST 4.10 software, both selective and non-selective HipHop
      pharmacophore maps for T-type CCBs were developed to identify its important
      common pharmacophoric features. HipHop pharmacophore map of the selective T-type
      CCBs contained six different chemical features, namely ring aromatic (R),
      positive ionizable (P), two hydrophobic aromatic (Y), hydrophobic aliphatic (Z),
      hydrogen bond acceptor (H) and hydrogen bond donor (D). However, non-selective T
      type CCBs contain all the above mentioned features except ring aromatic (R). The
      present ligand-based pharmacophore mapping approach could thus be utilized in
      classifying selective vs. non-selective T-type CCBs. Further, the model can be
      used for virtual screening of several small molecule databases.

PMID- 27713841
TI  - Late Effects: Focus on Adolescent and Young Adult Cancer Survivors.

PMID- 27713842
TI  - Clinically Relevant Four-Level Cancer-Related Fatigue Among Patients With Various
      Types of Cancer.

PMID- 27713843
TI  - Tyrosine Kinase Inhibitors for the Treatment of Chronic-Phase Chronic Myeloid
      Leukemia: Long-Term Patient Care and Management.
AB  - Several tyrosine kinase inhibitors (TKIs) are now approved for the treatment of
      chronic myeloid leukemia in chronic phase. The efficacy of these drugs has been
      repeatedly demonstrated, as has their tolerability in most patients. However,
      late and chronic toxicities become an important issue for many patients facing
      long-term TKI exposure. For patients on long-term imatinib, gastrointestinal
      events, fluid retention, muscle cramps, fatigue, and hepatotoxicity are among the
      most common and most clinically relevant adverse events (AEs). A few of these
      have also emerged as important AEs with some of the newer TKIs. Distinct long
      term toxicity concerns have emerged for dasatinib (pleural effusion, pulmonary
      hypertension, headache, and dyspnea) and nilotinib (rash, headache, myalgia,
      alopecia, and hyperglycemia), whereas due to the recent approval of bosutinib and
      ponatinib, their long-term toxicity profiles have not been fully characterized.
      Clinical experience with each of these drugs is accumulating, and ensuring proper
      adherence and monitoring for potential AEs is essential for effective treatment.

PMID- 27713844
TI  - Providing Intensive Palliative Care on an Inpatient Unit: A Full-Time Job.

PMID- 27713845
TI  - The First Oral Fixed-Dose Combination of Netupitant and Palonosetron for the
      Treatment of Chemotherapy-Induced Nausea and Vomiting.

PMID- 27713846
TI  - Advancements in Therapy for Acute Lymphoblastic Leukemia: Blinatumomab.

PMID- 27713847
TI  - Overview of the CLEOPATRA Trial: Implications for Advanced Practitioners.

PMID- 27713848
TI  - An Introduction to Survival Statistics: Kaplan-Meier Analysis.

PMID- 27713850
TI  - Abstracts From JADPRO Live at APSHO 2015.

PMID- 27713849
TI  - Suicide Screening in the Oncology Population.

PMID- 27713851
TI  - Swelling and Erythema of the Lower Extremities.

PMID- 27713852
TI  - Delayed cerebral infarct following anterior cervical diskectomy and fusion.
AB  - BACKGROUND: Ischemic stroke following anterior cervical diskectomy and fusion
      (ACDF) is an exceedingly rare complication. There are only three previous cases
      focusing on this problem in the literature; here, we present the fourth case.
      CASE DESCRIPTION: A patient, cared for at an outside institution, developed a
      delayed ischemic stroke 3 days following an ACDF. This complication was
      attributed to carotid manipulation precipitating vascular injury in the setting
      of multiple comorbid vascular and coagulopathic risk factors, including
      previously undiagnosed carotid atherosclerosis, a prior history of pulmonary
      embolus requiring Warfarin anticoagulation (held perioperatively), acute
      dehydration, and atrial fibrillation. CONCLUSIONS: This case demonstrates the
      importance of focused history and examination in appropriate patients prior to
      ACDF, with special consideration given to the significance of age, comorbidities
      including coagulopathy and arrhythmia, and potential underlying vascular disease
      as markers for increased risk of perioperative thrombotic stroke associated with
      carotid manipulation. Patients at higher risk warrant comprehensive preoperative
      assessment, including medical evaluation, carotid imaging, and consideration for
      alternative surgical approaches.

PMID- 27713853
TI  - Dual diagnostic catheter technique in the endovascular management of anterior
      communicating artery complex aneurysms.
AB  - BACKGROUND: The configuration of the anterior communicating artery (AcomA)
      complex is important in the endovascular treatment of AcomA complex aneurysms. In
      cases of codominant anterior cerebral arteries (ACA), coil embolization may
      result in inadvertent occlusion of the contralateral ACA due to poor
      visualization. A second diagnostic catheter in the contralateral carotid artery
      may help with visualization of this angiographic blind spot. To our knowledge,
      the safety and efficacy of this dual diagnostic catheter technique have never
      been assessed. METHODS: A cohort of consecutive patients that underwent coil
      embolization of an AcomA complex aneurysm at a major academic institution in the
      United States between 2007 and 2014 were retrospectively reviewed. RESULTS:
      Eighty-two patients who had an AcomA complex aneurysm treated with coil
      embolization were identified. The dual diagnostic catheter technique was used in
      17 (20.7%) patients. Aneurysms treated with the dual diagnostic catheter
      technique were less frequently ruptured and had less favorable dome-to-neck
      ratios as well as neck width for primary coil embolization. The rate of
      codominant ACAs was significantly higher and stent-assisted coil embolization was
      performed more frequently. The rate of thromboembolic complications, angiographic
      outcome, and retreatment did not differ between both the groups. CONCLUSIONS: The
      dual diagnostic catheter technique is a safe and effective method during coil
      embolization of AcomA complex aneurysms and preferred for aneurysms with
      codominant ACAs, incorporation of either A1 or A2 segments into the aneurysm, and
      aneurysms with a wide neck and low dome-to-neck ratios.

PMID- 27713854
TI  - Contralateral interlaminar approach for intraforaminal lumbar degenerative
      disease with special emphasis on L5-S1 level: A technical note.
AB  - BACKGROUND: Intraforaminal disc herniations at the L5-S1 level are extremely
      surgically challenging lesions. Intracanal approaches frequently require partial
      or total facetectomy, which may lead to instability. Solely extraforaminal
      approaches may offer limited visualization of the more medial superiorly exiting
      and inferiorly exiting nerve roots; this approach is also more complicated at L5
      S1 due to the often large L5 transverse process and the iliac wing. METHODS: Nine
      patients with intraforaminal L5-S1 disc herniations, foraminal stenosis, or
      synovial cysts underwent contralateral interlaminar approaches for lesion
      resection. Preoperative and postoperative visual analog scale scores were
      evaluated, and complications were reviewed. RESULTS: All 9 patients demonstrated
      immediate postoperative clinical improvement. None of the patients exhibited
      complications and none developed instability or neuropathic disorders.
      CONCLUSIONS: Although the number of cases in our sample was very small (9 in
      total), the contralateral interlaminar approach appeared to effectively address
      multiple degenerative L5-S1 foraminal pathologies. Large studies are needed to
      further evaluate the pros and cons of this approach.

PMID- 27713856
TI  - Rapid Eye Movement Sleep Homeostatic Response: A Potential Marker for Early
      Detection of Parkinson's Disease.

PMID- 27713857
TI  - On Being in the Wrong Place: The Role of Children's Conceptual Understanding and
      Ballgame Experience when Judging a Football Player's Offside Position.
AB  - We investigated the role of children's conceptual understanding and ballgame
      experience when judging whether a football player is in an offside position, or
      not. In the offside position, a player takes advantage of being behind the
      defence line of the opposing team and just waits for the ball to arrive in order
      to score a goal. We explained the offside rule to 7- and 9-year-old children with
      a Subbuteo setup. They produced drawings of an offside position until it was
      correct (drawing to criterion). Thereafter, children judged whether a designated
      player was in an offside position in a computerized task. Like adults, also
      children found it easier to judge when a player was in a wrong rather than a
      right place. Only when including frequency of ballgame practice in the analysis
      it was revealed that boys were better independently of age as they judged the
      offside position more systematically.

PMID- 27713855
TI  - Orthostatic Tremor: An Update on a Rare Entity.
AB  - BACKGROUND: Orthostatic tremor (OT) remains among the most intriguing and poorly
      understood of movement disorders. Compared to Parkinson's disease or even
      essential tremor, there are very few articles addressing more basic science
      issues. In this review, we will discuss the findings of main case series on OT,
      including data on etiology, pathophysiology, diagnostic approach, treatment
      strategies, and outcome. METHODS: Data for this review were identified by
      searching PUBMED (January 1966 to August 2016) for the terms "orthostatic tremor"
      or "shaky leg syndrome," which yielded 219 entries. We did not exclude papers on
      the basis of language, country, or publication date. The electronic database
      searches were supplemented by articles in the authors' files that pertained to
      this topic. RESULTS: Owing to its rarity, the current understanding of OT is
      limited and is mostly based on small case series or case reports. Despite this, a
      growing body of evidence indicates that OT might be a progressive condition that
      is clinically heterogeneous (primary vs. secondary cases) with a broader spectrum
      of clinical features, mainly cerebellar signs, and possible cognitive impairment
      and personality disturbances. Along with this, advanced neuroimaging techniques
      are now demonstrating distinct anatomical and functional changes, some of which
      are consistent with neuronal loss. DISCUSSION: OT might be a family of diseases,
      unified by the presence of leg tremor, but further characterized by etiological
      and clinical heterogeneity. More work is needed to understand the pathogenesis of
      this condition.

PMID- 27713858
TI  - Ascending colon cancer associated with deposited ova of Schistosoma japonicum in
      non-endemic area.
AB  - Some reports suggest the positive correlation between Schistosoma japonicum
      infection and colorectal cancer, however the sufficient evidence that supports a
      causal relationship between them has not been established. Japan used be an
      endemic area of S. japonicum infection for 40 years ago. But now all of Japan is
      a non-endemic area of S. japonicum infection. We report a case of ascending colon
      cancer associated with deposited ova of S. japonicum in non-endemic area.

PMID- 27713859
TI  - Chronic Q fever: A missed prosthetic valve endocarditis possibly for years.
AB  - Chronic Coxiella burnetii endocarditis usually develops in people with underlying
      heart disease and accounts for 60-70% of chronic Q fever. Onset is generally
      insidious and manifestations are atypical. The authors report a case of Coxiella
      burnetii prosthetic valve endocarditis in a 53 years- old patient with recurrent
      mechanical valve dehiscence on mitral position. He lived in a rural area with
      sheep and goats on the surroundings. During a 9 year- period, he was submitted to
      three cardiac mitral valve surgeries two of which with no Q fever diagnosis
      suspicion. Diagnosis was based on a positive serology test (Indirect
      imunofluorescence). Treatment consisted in a combination of prolonged course of
      hydroxychloroquine plus doxycycline and surgical replacement of the mitral valve,
      with a favorable outcome. With this case report, the authors pretend to highlight
      the not always expected diagnosis of Q fever endocarditis. If not considered,
      Coxiella burnetii endocarditis may lead to multiple cardiac surgeries, greater
      morbidity and potentially death.

PMID- 27713860
TI  - Melioidosis mimicking primary lung malignancy with superior vena cava
      obstruction.

PMID- 27713861
TI  - Anti-infective therapy without antimicrobials: Apparent successful treatment of
      multidrug resistant osteomyelitis with hyperbaric oxygen therapy.

PMID- 27713862
TI  - Pure Stage I Seminoma with an Elevated hCG of 25,265 mIU/ml: A Case Report.
AB  - We report a histologically pure stage 1 seminoma with an elevated human chorionic
      gonadotropin (hCG). A 38 year-old man was referred for the evaluation of the left
      testicular swelling. He showed an elevated serum hCG level of 25,265 mIU/ml with
      normal a fetoprotein and lactate dehydrogenase. Imaging showed heterogeneous
      tumor without any metastatic lesions. We conducted 4 courses of chemotherapy
      before detecting hCG nadir. The final pathological report showed pure seminoma
      with syncytiotrophoblastic cells but no choriocarcinoma components. The patient
      remains disease free until present time. The case raised several questions
      regarding diagnosis and treatment strategy for bulky testicular seminoma.

PMID- 27713863
TI  - Potential Impact on Clinical Decision Making via a Genome-Wide Expression
      Profiling: A Case Report.
AB  - Management of men with prostate cancer is fraught with uncertainty as physicians
      and patients balance efficacy with potential toxicity and diminished quality of
      life. Utilization of genomics as a prognostic biomarker has improved the informed
      decision-making process by enabling more rationale treatment choices. Recently
      investigations have begun to determine whether genomic information from tumor
      transcriptome data can be used to impact clinical decision-making beyond
      prognosis. Here we discuss the potential of genomics to alter management of a
      patient who presented with high-risk prostate adenocarcinoma. We suggest that
      this information help selecting patients for advanced imaging, chemotherapies, or
      clinical trial.

PMID- 27713864
TI  - Non-Radiographic Risk Factors Differentiating Atypical Lipomatous Tumors from
      Lipomas.
AB  - PURPOSE: To determine non-radiographic risk factors differentiating atypical
      lipomatous tumors (ALTs) from lipomas. METHODS: All patients with deep-seated
      lipomatous tumors of the extremities treated from January 2000 to October 2010
      were retrospectively reviewed. Factors reviewed included age, gender, tumor
      location, size, histology, local recurrence, dedifferentiation, and metastasis.
      Multivariate logistic regression models were used to evaluate the effects of
      patient characteristics on ALT status. RESULTS: Ninety-four lipomas and 46 ALTs
      were included. Patients with an ALT were older (median: 60.5 vs. 55 years).
      Lipomas were evenly distributed between upper (48.9%) and lower extremities
      (51.1%), whereas ALTs predominately involved the lower extremities (91.3%).
      Median ALT size (22 cm) was greater than lipomas (10 cm), p < 0.0001. One lipoma
      (1.04%) recurred at 77 months and five ALTs (10.9%) recurred at an average of 39
      months (19-64 months). Two ALTs originally treated with wide resection recurred
      with a dedifferentiated component and were treated with wide re-excision and
      chemotherapy. No metastases or tumor-related deaths occurred in either group at
      the time of last follow-up. Patients older than 60 years, tumors greater than 10
      cm, or thigh location, were more likely to be diagnosed with an ALT (p < 0.05).
      CONCLUSION: Lipomatous tumors were more likely to be ALTs when the tumor was at
      least 10 cm in size, located in the thigh, or found in patients that were 60
      years of age or older. These risk factors may be used to guide management and
      surveillance strategies, when lipomatous tumors do not display characteristic
      radiographic features.

PMID- 27713865
TI  - Characterization of the Adherence of Clostridium difficile Spores: The Integrity
      of the Outermost Layer Affects Adherence Properties of Spores of the Epidemic
      Strain R20291 to Components of the Intestinal Mucosa.
AB  - Clostridium difficile is the causative agent of the most frequently reported
      nosocomial diarrhea worldwide. The high incidence of recurrent infection is the
      main clinical challenge of C. difficile infections (CDI). Formation of C.
      difficile spores of the epidemic strain R20291 has been shown to be essential for
      recurrent infection and transmission of the disease in a mouse model. However,
      the underlying mechanisms of how these spores persist in the colonic environment
      remains unclear. In this work, we characterized the adherence properties of
      epidemic R20291 spores to components of the intestinal mucosa, and we assessed
      the role of the exosporium integrity in the adherence properties by using cdeC
      mutant spores with a defective exosporium layer. Our results showed that spores
      and vegetative cells of the epidemic R20291 strain adhered at high levels to
      monolayers of Caco-2 cells and mucin. Transmission electron micrographs of Caco-2
      cells demonstrated that the hair-like projections on the surface of R20291 spores
      are in close proximity with the plasma membrane and microvilli of
      undifferentiated and differentiated monolayers of Caco-2 cells. Competitive
      binding assay in differentiated Caco-2 cells suggests that spore-adherence is
      mediated by specific binding sites. By using spores of a cdeC mutant we
      demonstrated that the integrity of the exosporium layer determines the affinity
      of adherence of C. difficile spores to Caco-2 cells and mucin. Binding of
      fibronectin and vitronectin to the spore surface was concentration-dependent, and
      depending on the concentration, spore-adherence to Caco-2 cells was enhanced. In
      the presence of an aberrantly-assembled exosporium (cdeC spores), binding of
      fibronectin, but not vitronectin, was increased. Notably, independent of the
      exosporium integrity, only a fraction of the spores had fibronectin and
      vitronectin molecules binding to their surface. Collectively, these results
      demonstrate that the integrity of the exosporium layer of strain R20291
      contributes to selective spore adherence to components of the intestinal mucosa.

PMID- 27713868
TI  - The Effect of the Family Empowerment Model on Quality of Life in Children with
      Chronic Renal Failure: Children's and Parents' Views.
AB  - BACKGROUND: Chronic renal failure (CRF) causes a gradual decline in kidney
      function to the extent that CRF patients need long-term clinical care, which
      affects the patients' family function and quality of life (QoL). OBJECTIVES: The
      present study was conducted to study the effects of the family-centered
      empowerment model on QoL in children with CRF during 2012-2013. PATIENTS AND
      METHODS: In this quasi-experimental study, 68 children with CRF and their parents
      were randomly assigned to two groups, intervention and control, via a random
      numbers table. An empowerment program was then conducted over the course of seven
      45-minute sessions, and a questionnaire to ascertain demographic characteristics
      and the core pediatric QoL Inventory (version 4) were administered to both groups
      before the sessions and one month after the last training session. The data were
      analyzed using SPSS 20. RESULTS: The mean age of the children was 10.2 and 10.5
      years in the intervention and control groups, respectively. The duration of the
      disease was five years in both groups. Furthermore, a significant difference was
      seen in the mean score of the children's QoL from their own perspectives in the
      physical and psychosocial domains and the total QoL score in the intervention
      group before and after the training (P < 0.05). CONCLUSIONS: Since family
      centered empowerment interventions can determine the training- and treatment
      related needs of patients and are low cost and effective, they may help parents
      promote their children's self-efficacy and QoL.

PMID- 27713866
TI  - Hijacking Host Cell Highways: Manipulation of the Host Actin Cytoskeleton by
      Obligate Intracellular Bacterial Pathogens.
AB  - Intracellular bacterial pathogens replicate within eukaryotic cells and display
      unique adaptations that support key infection events including invasion,
      replication, immune evasion, and dissemination. From invasion to dissemination,
      all stages of the intracellular bacterial life cycle share the same three
      dimensional cytosolic space containing the host cytoskeleton. For successful
      infection and replication, many pathogens hijack the cytoskeleton using effector
      proteins introduced into the host cytosol by specialized secretion systems. A
      subset of effectors contains eukaryotic-like motifs that mimic host proteins to
      exploit signaling and modify specific cytoskeletal components such as actin and
      microtubules. Cytoskeletal rearrangement promotes numerous events that are
      beneficial to the pathogen, including internalization of bacteria, structural
      support for bacteria-containing vacuoles, altered vesicular trafficking, actin
      dependent bacterial movement, and pathogen dissemination. This review highlights
      a diverse group of obligate intracellular bacterial pathogens that manipulate the
      host cytoskeleton to thrive within eukaryotic cells and discusses underlying
      molecular mechanisms that promote these dynamic host-pathogen interactions.

PMID- 27713869
TI  - Short-Period Influence of Chronic Morphine Exposure on Serum Levels of Sexual
      Hormones and Spermatogenesis in Rats.
AB  - BACKGROUND: Increased rates of addiction and its broad societal complications are
      well known. One of the most important systems that may malfunction in drug
      abusers is the reproductive system, and evaluating patients for this potential
      risk may lead to increased awareness. MATERIALS AND METHODS: Thirty 60-day-old
      male rats were divided into control and target groups. The target group underwent
      5 mg/kg intraperitoneal injections of morphine twice a day while the control
      group underwent normal saline injections (at the same dosage). After 60 days, the
      rats were anesthetized, and after blood sampling, they underwent bilateral
      orchiepididymectomy. Histological and hormonal evaluations were performed on the
      samples. RESULTS: Levels of sex hormonal features and spermatogenesis were
      significantly reduced in the target group compared to the control group. LH
      levels showed a meaningful decrease in the target group, but FSH and testosterone
      levels did not. On histological section analysis, mature sperm were meaningfully
      decreased in the target group. CONCLUSIONS: Chronic use of opioids may lead to
      alterations in sexual features and sexual hormones. Therefore, opioids have the
      potential to cause infertility. These changes may result from the effect of the
      drugs on the hypophysis or hypothalamus, the direct effect of the drugs on the
      seminiferous tubules, or a combination of both. The findings suggest that public
      awareness about addiction may cause decreased infertility rates.

PMID- 27713867
TI  - Anaplasma phagocytophilum APH0032 Is Exposed on the Cytosolic Face of the
      Pathogen-Occupied Vacuole and Co-opts Host Cell SUMOylation.
AB  - Anaplasma phagocytophilum, a member of the family Anaplasmataceae and the
      obligate intracellular bacterium that causes granulocytic anaplasmosis, resides
      in a host cell-derived vacuole. Bacterial proteins that localize to the A.
      phagocytophilum-occupied vacuole membrane (AVM) are critical host-pathogen
      interfaces. Of the few bacterial AVM proteins that have been identified, the
      domains responsible for AVM localization and the host cell pathways that they co
      opt are poorly defined. APH0032 is an effector that is expressed and localizes to
      the AVM late during the infection cycle. Herein, the APH0032 domain that is
      essential for associating with host cell membranes was mapped. Immunofluorescent
      labeling of infected cells that had been differentially permeabilized confirmed
      that APH0032 is exposed on the AVM's cytosolic face, signifying its potential to
      interface with host cell processes. SUMOylation is the covalent attachment of a
      member of the small ubiquitin-like modifier (SUMO) family of proteins to lysines
      in target substrates. Previous work from our laboratory determined that
      SUMOylation is important for A. phagocytophilum survival and that SUMOylated
      proteins decorate the AVM. Algorithmic prediction analyses identified APH0032 as
      a candidate for SUMOylation. Endogenous APH0032 was precipitated from infected
      cells using a SUMO affinity matrix, confirming that the effector co-opts
      SUMOylation during infection. APH0032 pronouncedly colocalized with SUMO1, but
      not SUMO2/3 moieties on the AVM. Ectopic expression of APH0032 in A.
      phagocytophilum infected host cells significantly boosted the bacterial load.
      This study delineates the first domain of any Anaplasmataceae protein that is
      essential for associating with the pathogen-occupied vacuole membrane,
      demonstrates the importance of APH0032 to infection, and identifies it as the
      second A. phagocytophilum effector that co-opts SUMOylation, thus underscoring
      the relevance of this post-translational modification to infection.

PMID- 27713870
TI  - Comparison of Hemoglobin Levels Before and After Hemodialysis and Their Effects
      on Erythropoietin Dosing and Cost.
AB  - BACKGROUND: Hemoglobin levels measured after hemodialysis, as compared to
      hemoglobin levels measured before hemodialysis, are suggested to be a more
      accurate reflection of the hemoglobin levels between hemodialysis sessions, and
      to be a better reference point for adjusting erythropoietin dosing. OBJECTIVES:
      The aim of this study was to compare the hemoglobin levels before and after
      hemodialysis, to calculate the required erythropoietin doses based on these
      levels, and to develop a model to predict effective erythropoietin dosing.
      PATIENTS AND METHODS: In this cross-sectional study, the hemoglobin levels of 52
      patients with end-stage renal disease were measured before and after
      hemodialysis. The required erythropoietin doses and the differences in cost were
      calculated based on the hemoglobin levels before and after hemodialysis. A model
      to predict the adjusted erythropoietin dosages based on post-hemodialysis
      hemoglobin levels was proposed. RESULTS: Hemoglobin levels measured after
      hemodialysis were significantly higher than the hemoglobin levels before
      hemodialysis (11.1 +/- 1.1 vs. 11.9 +/- 1.2 g/dL, P < 0.001, 7% increase). The
      mean required erythropoietin dose based on post-hemodialysis hemoglobin levels
      was significantly lower than the corresponding erythropoietin dose based on pre
      hemodialysis hemoglobin levels (10947 +/- 6820 vs. 12047 +/- 7542 U/week, P <
      0.001, 9% decrease). The cost of erythropoietin was also significantly lower when
      post-hemodialysis levels were used (15.96 +/- 9.85 vs. 17.57 +/- 11.00
      dollars/patient/week, P < 0.001). This translated into 83.72 dollars/patient/year
      in cost reduction. The developed model for predicting the required dosage is:
      Erythropoietin (U/week) = 43540.8 + (-2734.8) * Post-hemodialysis Hb* (g/dL).
      [(R2) = 0.221; *P < 0.001]. CONCLUSIONS: Using post-hemodialysis hemoglobin
      levels as a reference point for erythropoietin dosing can result in significant
      dose and cost reduction, and can protect hemodialysis patients from
      hemoconcentration. The prediction of the erythropoietin adjusted dosage based on
      post-hemodialysis Hb may also help in avoiding overdosage.

PMID- 27713871
TI  - Sequence-identification of Candida species isolated from candidemia.
AB  - BACKGROUND: Candida species are the most prevalent cause of invasive fungal
      infections such as candidemia. Candidemia is a lethal fungal infection among
      immunocompromised patients worldwide. Main pathogen is Candida albicans but a
      global shift in epidemiology toward non-albicans species have reported. Species
      identification is imperative for good management of candidemia as a fatal
      infection. The aim of the study is to identify Candida spp. obtained from
      candidemia and determination of mortality rate among this population. MATERIALS
      AND METHODS: The study was performed during February 2014 to March 2015 in
      Tehran, Iran. Two-hundred and four blood cultures were evaluated for fungal
      bloodstream infection. Identification of isolates was carried out using
      phenotypic tests and polymerase chain reaction sequencing technique. RESULTS:
      Twenty-two out of 204 patients (10.8%) had candidemia. Candida parapsilosis was
      the most prevalent species (45.4%), followed by C. albicans (31.8%) and Candida
      glabrata (22.7%). Male to female sex ratio was 8/14. CONCLUSIONS: The emergence
      of resistant strains of Candida species should be considered by physicians to
      decrease the mortality of this fatal fungal infection by appropriate treatment.

PMID- 27713872
TI  - Prevalence of occult hepatitis B virus infection in hemodialysis patients in
      Isfahan, Iran.
AB  - BACKGROUND: The absence of a detectable hepatitis B surface antigen (HBsAg) with
      or without hepatitis B core antibody (anti-HBc) or hepatitis B surface antibody
      (anti-HBs) in the presence of hepatitis B virus-DNA (HBV-DNA) is defined as
      occult HBV infection. This study was aimed to evaluate the prevalence of occult
      HBV infection in patients receiving hemodialysis (HD) in Isfahan, Iran. MATERIALS
      AND METHODS: This cross sectional study was done on 400 patients without acute or
      chronic HBV infection with end-stage renal disease undergoing regular HD. Blood
      samples were collected prior to the HD session, and serological markers of viral
      hepatitis B included HBsAg, anti-HBs and anti-HBc were measured using standard
      third generation commercially available enzyme immunoassays kit, then samples of
      positive anti-HBc and negative anti-HBs were tested for HBV DNA using
      quantitative real-time polymerase chain reaction techniques. Data were analyzed
      by SPSS using t-test and Chi-square test. RESULTS: The mean age of patients was
      51.6 +/- 11.2 years. Anti-HBc positive was observed in 32 (8%) of 400 studied
      patients with negative HBsAg. Of 32 patients with anti-HBc positive, 15 were
      males and 17 were females with mean age of 49.7 +/- 12.6 years. Among 32 patients
      with anti-HBc positive, 10 patients were negative for anti-HBs. All of 10
      patients were negative for HBV DNA. The prevalence of occult HBV infection was
      0%. CONCLUSIONS: The prevalence of occult HBV infection in HBsAg negative
      patients undergoing HD was 0% and look to be among the lowest worldwide. So,
      occult HBV infection is not a significant health problem in HD patients in this
      region.

PMID- 27713873
TI  - Computed tomography-guided percutaneous core needle biopsy for diagnosis of
      mediastinal mass lesions: Experience with 110 cases in two university hospitals
      in Isfahan, Iran.
AB  - BACKGROUND: Computed tomography-guided percutaneous core needle biopsy (PCNB) is
      a diagnostic technique for initial assessment of mediastinal mass lesions. This
      study was conducted to evaluate its diagnostic yield and its complication rate.
      MATERIALS AND METHODS: We reviewed the records of CT-guided PCNB in 110 patients
      with mediastinal mass lesions performed in Kashani and Alzahra Hospitals,
      Isfahan, from 2006 to 2012. Gender, age at biopsy, size, and anatomic location of
      the lesion, number of passes, site of approach, complications, and final
      diagnosis were extracted. RESULTS: Our series encompasses 52 (47.2%) females and
      58 (52/7%) males with mean age of 41 +/- 8 years. The most common site of
      involvement was the anterior mediastinum (91.8% of cases). An average of 3/5
      passes per patient has been taken for tissue sampling. Parasternal site was the
      most frequent approach taken for PCNB (in 78.1% of cases). Diagnostic tissue was
      obtained in 99 (90%) biopsies while, in 11 (10%) cases, specimen materials were
      inadequate. Lymphoma (49.5%) and bronchogenic carcinoma (33.3%) were the most
      frequent lesions in our series. The overall complication rate was 17.2% from
      which 10.9% was pneumothorax, 5.4% was hemoptysis, and 0.9% was vasovagal reflex.
      CONCLUSION: CT-guided PCNB is a safe and reliable procedure that can provide a
      precise diagnosis for patients with both benign and malignant mediastinal masses,
      and it is considered the preferred first diagnostic procedure use for this
      purpose.

PMID- 27713874
TI  - The difference in correlation between insulin resistance index and chronic
      inflammation in type 2 diabetes with and without metabolic syndrome.
AB  - BACKGROUND: Insulin resistance (IR) is associated with low-grade systemic
      inflammation. It plays an important role in the pathogenesis of type 2 diabetes
      mellitus (T2DM) and cardiovascular disease (CVD) in patients with metabolic
      syndrome (MetS). It is unclear whether diabetic patients with MetS confer
      elevated CVD risk and outcomes beyond the impact of individual's components of
      MetS. The aim of this study is to highlight the central role of IR, inflammation,
      triglyceride/high-density lipoprotein- cholesterol (TG/HDL-C) ratio, and
      atherogenic index of plasma (AIP) in T2DM with MetS. MATERIALS AND METHODS: This
      cross-sectional study comprised 130 men distributed into three groups, namely
      Controls: 40 nondiabetic healthy volunteers; Group I: 40 T2DM patients without
      MetS, and Group II: 50 T2DM patients with MetS. Fasting blood samples were
      collected for the measurement of blood lipid profile, glucose, insulin,
      hemoglobin A1c, and high-sensitivity C-reactive protein (hs-CRP). TG/HDL-C ratio,
      AIP, and homeostasis model assessment of insulin resistance (HOMA-IR) were
      calculated. RESULTS: Significant positive association was observed between HOMA
      IR and hs-CRP only in Group II and between HOMA-IR and TG/HDL-C ratio in all
      subjects. Significant differences were seen in waist and hip circumferences,
      waist/hip ratio, body mass index, systolic blood pressure, fasting blood glucose,
      TGs, HDL-C, insulin, hs-CRP, HOMA-IR, TG/HDL ratio, and AIP between Controls and
      Group I with Group II. CONCLUSIONS: In T2DM with MetS, coexistence of elevated
      atherogenic indices, systemic inflammation, and association between HOMA-IR and
      TG/HDL-C ratio were seen. These factors are considered having important role in
      elevated CVD risk beyond MetS components in these patients.

PMID- 27713875
TI  - Symmetrical peripheral gangrene: Unusual complication of dengue fever.
AB  - Symmetrical peripheral gangrene (SPG) is a rare clinical entity, infective, and
      noninfective both types of etiologies are responsible. The basic underlying
      pathology in SPG is being disseminated intravascular coagulation and carries a
      high mortality. Here, we describe a 52-year-old male with dengue fever, who
      developed bilateral symmetrical dry gangrene of both hand and feet. His dengue
      IgM antibody was positive. All the peripheral pulses of the affected limbs were
      palpable. Color Doppler study of upper and lower limb vessels showed normal flow.
      The patient was managed with intravenous fluids, low molecular weight heparin,
      and fresh frozen plasma. His general condition was improved within 72 h with no
      further progression of gangrene. Clinician should suspect the possibility of SPG
      while dealing a case of dengue fever presenting as peripheral gangrene.

PMID- 27713876
TI  - The relationship between macro- and micro-nutrients intake and risk of preterm
      premature rupture of membranes in pregnant women of Isfahan.
AB  - BACKGROUND: Since preterm premature rupture of membranes (PPROM) is one of the
      most important complications of pregnancy and its relationship with nutrition
      status have not been surveyed comprehensively, we decided to study the
      relationship of maternal received nutrients (36 macro- and micro-nutrients) in
      three trimesters and PPROM which could be considered as a unique study. MATERIALS
      AND METHODS: In this prospective cohort study, data was collected by filling a
      questionnaire through interviews with 620 pregnant women who had no parameters to
      affect pregnancy outcome. 48-hr dietary recalls were completed for eligible women
      at 11th-15th, 26th, 34th-37th weeks of gestation. Physical activity was also
      assessed using a standard questionnaire. Also pregnant mother's reproductive and
      demographic characteristic and supplementation are considered. RESULTS: The mean
      value of received saturated fatty acids, polyunsaturated fatty acids and energy,
      in the first trimester (P < 0.001, P = 0.007, and P < 0.001 respectively), the
      mean values of calcium, sodium intake in the second trimester (P = 0.045, P =
      0.006, and P = 0.004 respectively), Vitamins C, A (mg), beta-carotene, cartenoids
      intake in the second trimester (P = 0.03, P = 0.001, P = 0.007, and P = 0.01
      respectively), and higher Vitamin C intake during the first trimester (P = 0.02)
      was significantly greater among subjects with PPROM compared to the others.
      CONCLUSIONS: The mean value of mentioned received nutrients in subjects who
      experienced PPROM later in pregnancy was higher than the others, which is
      independent of demographic and reproductive characteristic, estimated physical
      activity, and supplementation. Therefore, these findings could be considered in
      the nutritional programming for pregnant women to manage the risk of PPROM.

PMID- 27713877
TI  - The Spectrum of Congenital Heart Disease with Transposition of the Great Arteries
      from the Cardiac Registry of the University of Padua.
AB  - Transposition of the great arteries (TGA) is a cardiac condition in which the
      arterial trunks arise from the inappropriate ventricle: the aorta from the right
      ventricle and the pulmonary trunk from the left ventricle [discordant ventriculo
      arterial (VA) connection]. In complete TGA, the discordant VA connection is
      associated with situs solitus or inversus and concordant atrioventricular (AV)
      connection. The hemodynamic consequence of these combined connections is that
      systemic and pulmonary circulations function in "parallel" rather than in
      "series". The presence of situs solitus or inversus associated with both AV and
      VA discordant connections characterizes a different anatomical complex known as
      "corrected TGA." In these hearts, the double discordance at AV and VA levels
      permits a normal sequence of the blood flow from the right atrium to the
      pulmonary artery and from the left atrium to the aorta. The systemic and
      pulmonary circulation in these hearts functions regularly in series, and the
      blood sequence is "physiologically corrected." Thus, the term transposition,
      either complete or corrected, identifies two precise, different anatomical
      complexes, both characterized by VA discordance. However, among congenital heart
      disease (CHD), there are other anatomical complexes with discordant VA connection
      in the setting of isomeric atrial situs (right or left) or of univentricular AV
      connections (double inlet or absent connections). In these latter conditions, the
      term "transposition" is still necessary to stress that the great arteries are
      "transposed" in relation to the ventricular septum (aorta from the right
      ventricle and pulmonary trunk from the left ventricle) but certainly does not
      figure out the anatomical complexes named complete or corrected transposition. We
      reviewed the hearts with discordant VA connection of our Anatomical Collection,
      consisting of 1,640 specimens with CHD, with the aim to discuss the anatomy and
      the frequency of the anatomical variants of TGA and to clarify terminology and
      classification. The knowledge of the precise anatomy of these malformation are
      really important for clinical diagnosis and surgical planning.

PMID- 27713879
TI  - The Case for Endothelial Preservation via Pressure-Regulated Distension in the
      Preparation of Autologous Saphenous Vein Conduits in Cardiac and Peripheral
      Bypass Operations.

PMID- 27713878
TI  - ERK5 and Cell Proliferation: Nuclear Localization Is What Matters.
AB  - ERK5, the last MAP kinase family member discovered, is activated by the upstream
      kinase MEK5 in response to growth factors and stress stimulation. MEK5-ERK5
      pathway has been associated to different cellular processes, playing a crucial
      role in cell proliferation in normal and cancer cells by mechanisms that are both
      dependent and independent of its kinase activity. Thus, nuclear ERK5 activates
      transcription factors by either direct phosphorylation or acting as co-activator
      thanks to a unique transcriptional activation TAD domain located at its C
      terminal tail. Consequently, ERK5 has been proposed as an interesting target to
      tackle different cancers, and either inhibitors of ERK5 activity or silencing the
      protein have shown antiproliferative activity in cancer cells and to block tumor
      growth in animal models. Here, we review the different mechanisms involved in
      ERK5 nuclear translocation and their consequences. Inactive ERK5 resides in the
      cytosol, forming a complex with Hsp90-Cdc37 superchaperone. In a canonical
      mechanism, MEK5-dependent activation results in ERK5 C-terminal
      autophosphorylation, Hsp90 dissociation, and nuclear translocation. This
      mechanism integrates signals such as growth factors and stresses that activate
      the MEK5-ERK5 pathway. Importantly, two other mechanisms, MEK5-independent, have
      been recently described. These mechanisms allow nuclear shuttling of kinase
      inactive forms of ERK5. Although lacking kinase activity, these forms activate
      transcription by interacting with transcription factors through the TAD domain.
      Both mechanisms also require Hsp90 dissociation previous to nuclear
      translocation. One mechanism involves phosphorylation of the C-terminal tail of
      ERK5 by kinases that are activated during mitosis, such as Cyclin-dependent
      kinase-1. The second mechanism involves overexpression of chaperone Cdc37, an
      oncogene that is overexpressed in cancers such as prostate adenocarcinoma, where
      it collaborates with ERK5 to promote cell proliferation. Although some ERK5
      kinase inhibitors have shown antiproliferative activity it is likely that those
      tumors expressing kinase-inactive nuclear ERK5 will not respond to these
      inhibitors.

PMID- 27713880
TI  - An Algorithm Measuring Donor Cell-Free DNA in Plasma of Cellular and Solid Organ
      Transplant Recipients That Does Not Require Donor or Recipient Genotyping.
AB  - Cell-free DNA (cfDNA) has significant potential in the diagnosis and monitoring
      of clinical conditions. However, accurately and easily distinguishing the
      relative proportion of DNA molecules in a mixture derived from two different
      sources (i.e., donor and recipient tissues after transplantation) is challenging.
      In human cellular transplantation, there is currently no useable method to detect
      in vivo engraftment, and blood-based non-invasive tests for allograft rejection
      in solid organ transplantation are either non-specific or absent. Elevated levels
      of donor cfDNA have been shown to correlate with solid organ rejection, but
      complex methodology limits implementation of this promising biomarker. We
      describe a cost-effective method to quantify donor cfDNA in recipient plasma
      using a panel of high-frequency single nucleotide polymorphisms, next-generation
      (semiconductor) sequencing, and a novel mixture model algorithm. In vitro, our
      method accurately and rapidly determined donor:recipient DNA admixture. For in
      vivo testing, donor cfDNA was serially quantified in an infant with a urea cycle
      disorder after receiving six daily infusions of donor liver cells. Donor cfDNA
      isolated from 1 to 2 ml of recipient plasma was detected as late as 24 weeks
      after infusion suggesting engraftment. The percentage of circulating donor cfDNA
      was also assessed in pediatric and adult heart transplant recipients undergoing
      routine endomyocardial biopsy with levels observed to be stable over time and
      generally measuring <1% in cases without moderate or severe cellular rejection.
      Unlike existing non-invasive methods used to define the proportion of donor cfDNA
      in solid organ transplant patients, our assay does not require sex mismatch,
      donor genotyping, or whole-genome sequencing and potentially has broad
      application to detect cellular engraftment or allograft injury after
      transplantation.

PMID- 27713881
TI  - A Comparative Assessment of the Risks of Introduction and Spread of Foot-and
      Mouth Disease among Different Pig Sectors in Australia.
AB  - Small-scale pig producers are believed to pose higher biosecurity risks for the
      introduction and spread of exotic diseases than commercial pig producers.
      However, the magnitude of these risks is poorly understood. This study is a
      comparative assessment of the risk of introduction and spread of foot-and-mouth
      disease (FMD) through different sectors of the pig industry: (1) large-scale pig
      producers; (2) small-scale producers (<100 sows) selling at saleyards and
      abattoirs; and (3) small-scale producers selling through informal means. An
      exposure and consequence assessments were conducted using the World Organization
      for Animal Health methodology for risk analysis, assuming FMD virus was
      introduced into Australia through illegal importation of infected meat. A
      quantitative assessment, using scenario trees and Monte Carlo stochastic
      simulation, was used to calculate the probabilities of exposure and spread. Input
      data for these assessments were obtained from a series of data gathering
      exercises among pig producers, industry statistics, and literature. Findings of
      this study suggest there is an Extremely low probability of exposure (8.69 * 10-6
      to 3.81 * 10-5) for the three sectors of the pig industry, with exposure through
      direct swill feeding being 10-100 times more likely to occur than through contact
      with infected feral pigs. Spread of FMD from the index farm is most likely to
      occur through movement of contaminated fomites, pigs, and ruminants. The virus is
      more likely to spread from small-scale piggeries selling at saleyards and
      abattoirs than from other piggeries. The most influential factors on the spread
      of FMD from the index farm is the ability of the farmer to detect FMD, the
      probability of FMD spread through contaminated fomites and the presence of
      ruminants on the farm. Although small-scale producers selling informally move
      animals less frequently and do not use external staff, movement of pigs to non
      commercial pathways could jeopardize animal traceability in the event of a
      disease outbreak. This study suggests that producers' awareness on and engagement
      with legislative and industry requirements in relation to biosecurity and
      emergency animal disease management needs to be improved. Results from this study
      could be used by decision-makers to prioritize resource allocation for improving
      animal biosecurity in the pig industry.

PMID- 27713882
TI  - Current epidemiology of sepsis in mainland China.
AB  - The disease burden of sepsis is a global issue. Most of the large-scale
      epidemiological investigations on sepsis have been carried out in developed
      countries. The population of 1.3 billion in mainland China accounts for
      approximately 1/5th of the whole world population. Thus, the knowledge of the
      incidence and mortality of sepsis in mainland China is vital before employing
      measures for its improvement. However, most of the epidemiological data of sepsis
      in mainland China was obtained from ICU settings, and thus lacks the population
      based incidence and mortality of sepsis. In the present review, we summarized the
      limited literature encompassing the incidence, mortality, long-term outcome, and
      pathogens of sepsis in mainland China. Therefore, it might provide some valuable
      information regarding the sepsis disease burden and current issues in the
      management of sepsis in mainland China.

PMID- 27713883
TI  - Epidemiologic trends of sepsis in western countries.
AB  - Since the American College of Chest Physicians (ACCP) and the Society of Critical
      care Medicine (SCCM) published the first consensus definition of syndromes
      related to sepsis in 1992, the knowledge of epidemiology of sepsis has clearly
      improved, although no prospective studies have been performed to analyse the
      incidence of sepsis in general population. There are differences in epidemiologic
      trends in sepsis between western countries and low-income and middle-income
      countries. In the United States (US), most of epidemiologic studies have been
      based on large, administrative databases, reporting an increase in the incidence
      of severe sepsis over years. In general, studies describing epidemiology of
      sepsis outside the US use clinical definitions and intensive care unit (ICU)
      observational cohort designs instead of administrative databases and definitions.
      Incidence of sepsis has increased over years, probably due to progressive aging
      of population, the existence of more comorbidities and maybe the liberal use of
      sepsis codification, by including patients with less severity. Notwithstanding,
      mortality due to sepsis is clearly decreasing over years, probably to improvement
      in ICU care, although absolute mortality is growing on account of the raise in
      incidence. Risk factors for sepsis are the two ends of life, male sex, US black
      race, presence of comorbidities and certain genetic variants. Respiratory tract
      infections are the most common source of sepsis, and, nowadays, Gram-positive
      infections are more frequent that Gram-negative sepsis in most prospective
      studies.

PMID- 27713885
TI  - The immunocompromised oncohematological critically ill patient: considerations in
      severe infections.
AB  - Sepsis and septic shock remain a major cause of mortality among critically ill
      patient. This is particularly relevant among cancer patients as highlighted by
      different series showing that up to one in five patients admitted to intensive
      care units (ICU) with sepsis have cancer, and also, sepsis is a leading reason
      for ICU admission in patients with cancer. The classic predictors of mortality
      among these patients (such as cancer lineage, neutropenia degree, or bone marrow
      transplantation history) have changed during the last decades, and they should no
      longer be used to rule out ICU admission. Instead, a newer approach to these
      patients should be performed taking into account organ failure assessment and
      prior performance status. When a doubt exists about the criteria for ICU
      admission, not only a trial of ICU management should be proposed to assert that
      no patients are withhold of the opportunity for recovering from the acute
      condition, but also an early admission, to prevent more derangement, and thus
      impact on mortality.

PMID- 27713884
TI  - Resistance mechanisms.
AB  - By definition, the terms sepsis and septic shock refer to a potentially fatal
      infectious state in which the early administration of an effective antibiotic is
      the most significant determinant of the outcome. Because of the global spread of
      resistant bacteria, the efficacy of antibiotics has been severely compromised. S.
      pneumonia, Escherichia coli (E. coli), Klebsiella, Acinetobacter, and Pseudomonas
      are the predominant pathogens of sepsis and septic shock. It is common for E.
      coli, Klebsiella, Acinetobacter and Pseudomonas to be resistant to multiple
      drugs. Multiple drug resistance is caused by the interplay of multiple resistance
      mechanisms those emerge via the acquisition of extraneous resistance determinants
      or spontaneous mutations. Extended-spectrum beta-lactamases (ESBLs),
      carbapenemases, aminoglycoside-modifying enzymes (AMEs) and quinolone resistance
      determinants are typically external and disseminate on mobile genetic elements,
      while porin-efflux mechanisms are activated by spontaneous modifications of
      inherited structures. Porin and efflux mechanisms are frequent companions of
      multiple drug resistance in Acinetobacter and P. aeruginosa, but only
      occasionally detected among E. coli and Klebsiella. Antibiotic resistance became
      a global health threat. This review examines the major resistance mechanisms of
      the leading microorganisms of sepsis.

PMID- 27713887
TI  - New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ
      failure.
AB  - Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its
      half-life is several hours, and its plasma concentrations can be determined in
      clinical practice, it is essentially irrelevant, but proportionally represents
      the levels and activity of adrenomedullin (ADM). ADM synthesis is widely
      distributed in tissues, including bone, adrenal cortex, kidney, lung, blood
      vessels and heart. Its fundamental biological effects include vasodilator,
      positive inotropic, diuretic, natriuretic and bronchodilator. It has been
      described high levels in septic patients, interacting directly with the
      relaxation of vascular tone, triggering hypotension of these patients. It is also
      found high levels in other diseases such as hypertension, heart failure,
      respiratory failure, renal failure, cirrhosis and cancer. MR-proADM has been
      identified as a prognostic marker, stratifying the mortality risk in patients
      with sepsis in emergency department (ED) and ICU. Evolutionary MR-proADM levels
      and clearance marker to the 2nd-5th days of admission help to determine the poor
      performance and the risk of mortality in patients with severe sepsis admitted to
      the ICU. The MR-proADM levels are more effective than procalcitonin (PCT) and C
      reactive protein (CRP) levels to determine an unfavorable outcome and the risk of
      mortality in patients with sepsis admitted to the ICU. It has also proved useful
      in patients diagnosed with organ dysfunction of infectious etiology. MR-proADM
      levels are independent of the germ conversely it is related to the magnitude of
      organ failure and therefore severity. We consider advisable incorporating the MR
      proADM the panel of biomarkers necessary for the diagnosis and treatment of
      critically ill patients admitted to the ICU with severe sepsis. The combined PCT
      and MR-proADM levels could represent a valid tool in the clinical practice to
      timely identify patients with bacterial infections and guide the diagnosis and
      treatment of sepsis and septic shock.

PMID- 27713886
TI  - The role of genetics and antibodies in sepsis.
AB  - During the course of sepsis when immunosuppression predominates, the
      concentrations of circulating immunoglobulins (IGs) are decreased and this is
      associated with adverse outcomes. The production of IGs as response to invasive
      bacterial pathogens takes place through a complex pathway starting from the
      recognition of the antigen (Ag) by innate immune cells that process and present
      Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs
      specific B cells and ends with the production of IGs by plasma cells. All
      molecules implicated in this process are encoded by genes bearing single
      nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown
      that the carriage of minor frequency SNPs of CD14, TLR2 and TNF is associated
      with increased sepsis risk. The ambiguity of results of clinical trials studying
      the clinical efficacy of exogenous IG administration in sepsis suggests that
      efficacy of treatment should be considered after adjustment for SNPs of all
      implicated genes in the pathway of IG production.

PMID- 27713888
TI  - Current understanding in source control management in septic shock patients: a
      review.
AB  - Sepsis and septic shock is one of the leading causes of death worldwide.
      Antibiotics, fluid resuscitation support of vital organ function and source
      control are the cornerstones for the treatment of these patients. Source control
      measures include all those actions taken in the process of care to control the
      foci of infection and to restore optimal function of the site of infection.
      Source control represents the multidisciplinary team required in order to
      optimize critical care for septic shock patients. In the last decade an increase
      interest on fluids, vasopressors, antibiotics, and organ support techniques in
      all aspects whether time, dose and type of any of those have been described.
      However information of source control measures involving minimal invasion and new
      techniques, time of action and outcome without it, is scarce. In this review the
      authors resumes new information, recommendations and future directions on this
      matter when facing the more common types of infections.

PMID- 27713889
TI  - Right first time!
AB  - Septic shock is still a lethal disease in intensive care units (ICU). The
      mortality can exceed 40% even with therapeutic management. The high mortality is
      clearly associated with the delay of appropriate antimicrobial therapy. Early
      diagnosis and identification of infectious source is the mainstay of optimal
      therapeutic management. On the other hand, source control and optimize antibiotic
      dosing according to pharmacokinetics (PK)/pharmacodynamics (PD) properties of
      antibiotics and organ dysfunction of patients are required to get the best
      clinical outcome.

PMID- 27713890
TI  - Implementing sepsis bundles.
AB  - Sepsis bundles represent key elements of care regarding the diagnosis and
      treatment of patients with septic shock and allow ones to convert complex
      guidelines into meaningful changes in behavior. Sepsis bundles endorsed the early
      goal-directed therapy (EGDT) and their implementation resulted in an improved
      outcome of septic shock patients. They induced more consistent and timely
      application of evidence-based care and reduced practice variability. These
      benefits mainly depend on the compliance with sepsis bundles, highlighting the
      importance of dedicated performance improvement initiatives, such as multifaceted
      educational programs. Nevertheless, the interest of early goal directed therapy
      in septic shock patients compared to usual care has recently been questioned,
      leading to an update of sepsis bundles in 2015. These new sepsis bundles may also
      exhibit, as the previous bundles, some limits and pitfalls and the effects of
      their implementation still needs to be evaluated.

PMID- 27713893
TI  - Design and Psychometric Properties of Male Adolescent Health Needs-Assessment
      Scale.
AB  - BACKGROUND: Given the importance of adolescents' health in establishing health in
      the newly thriving generation of every society, the first step for adolescents'
      health promotion is health needs assessment. The present study was, therefore,
      conducted to design a valid and reliable scale for health needs assessment of
      male adolescents. METHODS: This is an exploratory sequential mixed method study
      (2014-2015). The qualitative part was performed using content analysis approach
      and aimed to generate items pool. Data collection was performed by 7 focus group
      discussions with 51 male adolescents, and 10 semi-structured in-depth interviews
      with 10 other adolescents. Nine further in-depth interviews were also performed
      with 9 key informants. Purposive sampling was used and continued until data
      saturation. In the quantitative part, the designed scale was psychometrically
      assessed through the examination of the face and content validities using
      qualitative and quantitative methods and also the construct validity using the
      exploratory factor analysis along with the tool's internal consistency and
      stability. RESULTS: The content analysis of the data from the qualitative part
      led to the extraction of 4 main themes and 103 items, which moved to the
      quantitative stage. The mean content validity index of the scale was estimated
      0.91 and content validity ratio was 0.89. The exploratory factor analysis showed
      4 factors for the designed scale (49 items), including physical, psychological,
      social and sexual health needs. The internal consistency and the stability
      assessment of the scale showed 0.79 and 0.89, respectively. (P<0.001).
      CONCLUSION: According to the psychometric assessment, MAHNAS is a valid and
      reliable scale compatible with the Iranian culture that can be used in the health
      needs assessment of male adolescents.

PMID- 27713892
TI  - Effects of a Lifestyle Modification Program on Knowledge, Attitude and Practice
      of Hypertensive Patients with Angioplasty: A Randomized Controlled Clinical
      Trial.
AB  - BACKGROUND: Lack of knowledge, attitude and practice are some of the barriers of
      having a healthy lifestyle and controlling high blood pressure. This study aimed
      to determine the effectiveness of a lifestyle modification program on knowledge,
      attitude and practice of hypertensive patients with angioplasty. METHODS: This
      study was a randomized controlled clinical trial conducted from November to April
      2014 on 60 hypertensive patients with angioplasty in Shahid Chamran hospital of
      Isfahan, Iran. The samples were randomly assigned to two equal groups. Data
      collection was performed in three stages by a researcher-made questionnaire. The
      intervention plan was 6 education sessions and then follow up were done by phone
      call. The gathered data were analyzed via SPSS (V.20), using t-test, Chi-square,
      repeated measurement, and post hoc LSD test and ANOVA statistics. RESULTS: The
      mean score of knowledge, attitude and practice in the experimental group
      immediately after the intervention was 77.8+/-7.2, 88.3+/-6.4 and 86.2+/-6.5,
      respectively and one month after the intervention was 80.8+/-7.4, 91.1+/-3.5 and
      92.5+/-2.2, respectively. But in the control group, the mean score of knowledge,
      attitude and practice immediately after the intervention (34.90+/-11.23, 61.11+/
      6.28, and 38.64+/-7.15) and one month after the intervention was (38.64+/-7.15,
      59.56+/-6.31 and 37.27+/-7.26. CONCLUSION: Lifestyle modification program can be
      effective in promoting the knowledge, attitude and practice of hypertensive
      patients with angioplasty. Nurses can use this program in their care provision
      programs for these patients. Trial Registration Number:IRCT2015062420912N3.

PMID- 27713891
TI  - Vasoactive agents for the treatment of sepsis.
AB  - The article describes some commonly used vasoactive agents in patients with
      septic shock. Depending on their distinct pharmacological properties, their
      effects on vascular bed and cardiac function are different. For example, dopamine
      has equivalent effect on heart and vasculature, which can result in increases in
      cardiac output, mean arterial pressure and heart rate. Dobutamine is considered
      as inodilator because it has potent effect on cardiac systole and vasculature.
      Patients with sepsis and septic shock sometimes have coexisting cardiac
      dysfunction that justifies the use of dobutamine. Levosimendan is a relatively
      new agent exerting its inodilator effect by increasing sensitivity of myocardium
      to calcium. Some preliminary studies showed a promising result of levosimendan on
      reducing mortality.

PMID- 27713894
TI  - Pain Experience in Hemophilia Patients: A Hermeneutic Phenomenological Study.
AB  - BACKGROUND: Pain, as a crucial subsequence of joint hemorrhages in hemophilia
      patients, is chronic, debilitating, and distracting. This study aimed to describe
      and interpret pain experiences of hemophilia patients in their lives. METHODS:
      This qualitative study with hermeneutic phenomenological approach was conducted
      on fourteen hemophilia patients who had been referred to a hemophilia center
      affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. The study
      question was "what is the meaning of pain in hemophilia patients' lives? The data
      were collected through semi-structured interviews and field notes through
      purposeful sampling. Then, thematic analysis with van Manen's six-step
      methodological framework was used. MAX.QDA qualitative software package, 2010,
      was used to analyze the data. RESULTS: The three main themes that emerged in this
      study were "alteration in physical health", "engagement in psychological
      problems", and "impairment in social relationships". Alteration in physical
      health consisted of three subthemes, namely "impairment of physical function",
      "change in body physics", and "disturbance in sleep quality". In addition, two
      subthemes including "nostalgia of pain in adults with hemophilia" and
      "psychological distress" emerged from engagement in psychological problems.
      Finally, "loss of social activity" and "change in relationships" were related to
      impairment in social relationships. CONCLUSION: The present study highlighted
      alteration in physical health, engagement in psychological problems, and
      impairment in social relationship as a result of pain in hemophilia patients.
      Thus, healthcare providers and family members have to pay special attention to
      these problems. Besides, providing complementary therapy interventions is
      suggested for reducing these issues.

PMID- 27713895
TI  - Effectiveness of Cognitive Behavioral Therapy on the Quality of Sleep in Women
      with Multiple Sclerosis: A Randomized Controlled Trial Study.
AB  - BACKGROUND: Multiple sclerosis is accompanied by secondary clinical signs such as
      insomnia. Considering the side effects of drugs and also increasing acceptability
      of psychotherapy methods in health systems, we aimed to determine the effect of
      group cognitive behavioral therapy on the quality of sleep in women with multiple
      sclerosis in 2014. METHODS: This study is a randomized controlled clinical
      conducted on 72 women with multiple sclerosis who referred to medical centers of
      Isfahan. After convenience sampling, participants were randomly allocated into
      two equal groups of control (n=36) and intervention (n=36). In the intervention
      group, cognitive behavioral therapy was performed in 8 sessions. The control
      group, along with receiving the common drugs, participated in 3 group sessions
      and talked about their feelings and experiences. Data were gathered using
      Pittsburgh Sleep Quality Index (PSQI) and analyzed through independent t-test,
      Chi-square, Mann Whitney, ANOVA with repeated measure, using SPSS 18. RESULTS:
      There was a significant difference between the mean score of sleep quality of the
      control and intervention groups immediately and one month after the intervention
      (P<0.001). ANOVA with repeated measure test showed that the mean score of sleep
      quality of patients in the intervention group had a significant difference at
      three stages of before, immediately and one month after the intervention.
      CONCLUSIONS: According to the results of this study, cognitive behavioral
      therapy, as an effective and cost-effective therapy, could improve sleep quality
      in patients with multiple sclerosis. Trial Registration Number:
      IRCT2015012720833N1.

PMID- 27713896
TI  - Nurses' Empowerment in Self-Care Education to Stroke Patients: An Action Research
      Study.
AB  - BACKGROUND: Self-care needs are major problems among stroke patients. Nurses can
      support them through interventions such as education, a change in their attitude
      and emphasis on their remaining abilities. However, research has shown some weak
      points in the quality of care given to these patients. So the aim of this study
      was to improve the nurses' practice in self-care education to stroke patients.
      METHODS: The findings of evaluation phase showed that during action research,
      approaching the nurses' empowerment in self-care education to stroke patients has
      been set in motion. The nursing practice improvement, knowledge based practice,
      nurses' attitude change, ability to respond against routinization, and motivation
      promotion emphasize the success of change process. Facilitators and barriers of
      educating patients are acknowledged by the participants as a factor influencing
      the continuation of change. RESULTS: The lack of nurses' educating performance
      skills was overcome using action research and changes were made to improve the
      performance of nurses. CONCLUSIONS: The lack of nurses' educating performance
      skills was overcome using action research and changes were made to improve the
      performance of nurses.

PMID- 27713897
TI  - Psychological Empowerment Model in Iranian Pregnant Women.
AB  - BACKGROUND: Women's empowerment programs during pregnancy focus primarily on
      increasing women's health goals and psychological empowerment has been considered
      important in most issues related to pregnant mothers' mental health. Using path
      analysis, this study aims to examine the direct and indirect components of
      psychological empowerment of pregnant mothers. METHODS: This model-testing study
      was conducted in Gorgan, northwest of Iran during three months in spring of 2015.
      Through random cluster sampling, a total number of 160 pregnant women were
      selected from 10 urban medical centers and clinics as primary centers. We used
      Spritzer's Psychological empowerment scale. Suitable sampling based on Nunally
      and Bernstein was followed in the model. The relationships between the dependent
      variables were then examined by means of path analysis using Amos 18. RESULTS:
      The psychological empowerment of pregnant mothers (PEPW) model is impacted by
      individual factors, such as marriage age and employment, including some
      subjectively rated factors such as marital satisfaction and experience of
      violence. The PEPW model was deemed appropriate as optimum conditions indicators
      of goodness of fit; low index of chi2/df shows little difference between the
      conceptual model and observed data, while RMSEA value indicated the goodness of
      fit. Other indicators such as CMIN=0.957, CMIN/DF=0.957, P-CLOSE=0.418,
      chi2=0.957 and probability level=0.328 the fact that the model is ideal. The
      mothers' employment had the highest coefficient in the PEPW path model .731
      (0.443, 0.965) bootstrap confidence intervals by 95%, and with a p-value of less
      than 0.05. CONCLUSIONS: The mothers' employment is the most important factor in
      psychological empowerment, but it cannot be addressed quickly. Programming to
      increase marital satisfaction followed by a decrease in family violence and
      prevention of early marriage are necessary for promotion of psychological
      empowerment during pregnancy.

PMID- 27713899
TI  - Relationship between Gender Roles and Sexual Assertiveness in Married Women.
AB  - BACKGROUND: Evidence indicates that sexual assertiveness is one of the important
      factors affecting sexual satisfaction. According to some studies, traditional
      gender norms conflict with women's capability in expressing sexual desires. This
      study examined the relationship between gender roles and sexual assertiveness in
      married women in Mashhad, Iran. METHODS: This cross-sectional study was conducted
      on 120 women who referred to Mashhad health centers through convenient sampling
      in 2014-15. Data were collected using Bem Sex Role Inventory (BSRI) and Hulbert
      index of sexual assertiveness. Data were analyzed using SPSS 16 by Pearson and
      Spearman's correlation tests and linear Regression Analysis. RESULTS: The mean
      scores of sexual assertiveness was 54.93+/-13.20. According to the findings,
      there was non-significant correlation between Femininity and masculinity score
      with sexual assertiveness (P=0.069 and P=0.080 respectively). Linear regression
      analysis indicated that among the predictor variables, only Sexual function
      satisfaction was identified as the sexual assertiveness summary predictor
      variables (P=0.001). CONCLUSION: Based on the results, sexual assertiveness in
      married women does not comply with gender role, but it is related to Sexual
      function satisfaction. So, counseling psychologists need to consider this
      variable when designing intervention programs for modifying sexual assertiveness
      and find other variables that affect sexual assertiveness.

PMID- 27713898
TI  - Factors Influencing School Health in Elementary Schools in Isfahan, Iran: A
      Qualitative Study.
AB  - BACKGROUND: Students' health and future health of the community are related to
      providing health care in schools and since in every society, different contextual
      factors affect this matter, the present study aims to recognize the factors
      influencing the health care elementary students are provided with. METHODS: This
      qualitative content analysis was performed in 2014 in Isfahan. This study was
      conducted on school health instructors of elementary schools. Through targeted
      sampling, 15 health care providers, two mothers and 3 principals from 23
      elementary schools were selected. Twenty-two semi-structured interviews were
      performed. Qualitative data analysis was done using qualitative content analysis.
      RESULTS: In this study, 3 concepts were extracted: family umbrella over health
      (with two sub-categories of 'family's social status and its effect on health' and
      'family and health'), functional resources (with two sub-categories of
      'opportunity', 'availability of resources for diagnosis') and health components
      (with two sub-categories of 'culture', 'the value of school health'). These
      contextual factors must be considered in providing health care for schools.
      CONCLUSIONS: Consideration of effective contextual factors on providing
      elementary students with health care can help improve health for this group.

PMID- 27713900
TI  - The Burden of Care: Mothers' Experiences of Children with Congenital Heart
      Disease.
AB  - BACKGROUND: Mothers play a key role in caring for their sick children. Their
      experiences of care were influenced by culture, rules, and the system of health
      and care services. There are few studies on maternal care of children with
      congenital heart disease. Also, each of them has studied a particular aspect of
      care. The present research aimed to understand care experiences of mothers of
      children with congenital heart disease. METHODS: A conventional content analysis
      was used to obtain rich data. The goal of content analysis is "to provide
      knowledge and deeper understanding of the phenomenon under the study". The study
      was conducted in Kerman, Iran in 2014, on mothers of children with CHD. The
      purposive sampling technique was used to select the participants. Participants
      were 14 mothers of children with CHD and one father and one nurse of open heart
      surgery unit, from two hospitals affiliated with Kerman University of Medical
      Sciences. Eighteen semi-structured interviews were constructed. Data were
      analyzed using conventional content analysis. MAXQDA 2007 software (VERBI GmbH,
      Berlin, Germany) was used to classify and manage the coding. Constant comparative
      method was done for data analysis. The reliability and validity of the findings,
      including the credibility, confirm ability, dependability, and transferability,
      were assessed. RESULTS: According to the content analysis, the main theme was the
      catastrophic burden of child care on mothers that included three categories: 1)
      the tension resulting from the disease, 2) involvement with internal thoughts,
      and 3) difficulties of care process. CONCLUSION: The results of this study may
      help health care professionals to provide supportive and educational packages to
      the patients, mothers and Family members until improving the management of
      patient's care.

PMID- 27713901
TI  - Resilience and Its Contributing Factors in Adolescents in Long-Term Residential
      Care Facilities Affiliated to Tehran Welfare Organization.
AB  - BACKGROUND: Resilience is a quality that affects an individual's ability to cope
      with tension. The present study was conducted to determine resilience and its
      contributing factors in high-risk adolescents living in residential care
      facilities affiliated to Tehran Welfare Organization in order to help develop
      effective preventive measures for them. METHODS: The present descriptive study
      was conducted on 223 adolescents living in 15 different governmental residential
      care centers in 2014. Participants were selected through convenience sampling.
      The data required were collected via the Wagnild and Young Resilience Scale with
      content validity (S-CVI=0.92) and a reliability of alpha=0.77 and r=0.83
      (P<0.001). The data obtained were analyzed in SPSS-20 using descriptive and
      inferential statistics including Chi-square test, independent t-test and ANOVA.
      RESULTS: The adolescents' mean score of resilience was 84.41+/-11.01. The level
      of resilience was moderate in 46.2% of the participants and was significantly
      higher in the female than in the male adolescents (P=0.006); moreover, the score
      obtained was lower in primary school children as compared to middle school and
      high school students (P<0.001). CONCLUSION: Directors of care facilities and
      residential care personnel should adopt preventive resilience-based strategies in
      order to optimize resilience among adolescents, particularly the male. It is
      important to provide a basis to prevent adolescents' academic failure and place a
      stronger value on education than the past.

PMID- 27713902
TI  - Absence of Nursing Position in the new Health Policies in Iran: A Dialogue with
      Nursing Scholars and Nursing Managers.

PMID- 27713903
TI  - Assessing Academic Self-Efficacy, Knowledge, and Attitudes in Undergraduate
      Physiology Students.
AB  - Academic self-efficacy affects the success of students in the sciences. Our goals
      were to develop an instrument to assess the self-efficacy and attitudes toward
      science of students in an undergraduate physiology course. We hypothesized 1)
      that our instrument would demonstrate that students taking this course would
      exhibit greater self-efficacy and more positive attitudes toward science than
      students in a non-science undergraduate course, and 2) that the physiology
      students' self-efficacy and attitudes would improve after completing the course.
      A 25-question survey instrument was developed with items investigating
      demographic information, self-efficacy, content knowledge, confidence, and
      attitudes regarding science. Students in either an undergraduate physiology
      course (Group P) or a history course (Group H) completed the survey. Forty-eight
      students in Group P completed both PRE- and POST-class surveys, while 50 students
      in Group H completed the pre-class survey. The academic self-efficacy of Group P
      as assessed by the PRE-survey was significantly higher than Group H (p=0.0003).
      Interestingly, there was no significant difference between groups in content
      knowledge in the PRE-survey. The self-efficacy of Group P was significantly
      higher as assessed by the POST-survey, when compared to the PRE-survey (p<0.0001)
      coincident with an improvement (p<0.001) in content knowledge for Group P in the
      POST-survey. This study established a survey instrument with utility in assessing
      self-efficacy, attitudes, and content knowledge. Our approach has applicability
      to studies designed to determine the impact of instructional variables on
      academic self-efficacy, attitudes, and confidence of students in the sciences.

PMID- 27713904
TI  - A Synthesis of Current Surveillance Planning Methods for the Sequential
      Monitoring of Drug and Vaccine Adverse Effects Using Electronic Health Care Data.
AB  - INTRODUCTION: The large-scale assembly of electronic health care data combined
      with the use of sequential monitoring has made proactive postmarket drug- and
      vaccine-safety surveillance possible. Although sequential designs have been used
      extensively in randomized trials, less attention has been given to methods for
      applying them in observational electronic health care database settings. EXISTING
      METHODS: We review current sequential-surveillance planning methods from
      randomized trials, and the Vaccine Safety Datalink (VSD) and Mini-Sentinel Pilot
      projects-two national observational electronic health care database safety
      monitoring programs. FUTURE SURVEILLANCE PLANNING: Based on this examination, we
      suggest three steps for future surveillance planning in health care databases:
      (1) prespecify the sequential design and analysis plan, using available
      feasibility data to reduce assumptions and minimize later changes to initial
      plans; (2) assess existing drug or vaccine uptake, to determine if there is
      adequate information to proceed with surveillance, before conducting more
      resource-intensive planning; and (3) statistically evaluate and clearly
      communicate the sequential design with all those designing and interpreting the
      safety-surveillance results prior to implementation. Plans should also be
      flexible enough to accommodate dynamic and often unpredictable changes to the
      database information made by the health plans for administrative purposes.
      CONCLUSIONS: This paper is intended to encourage dialogue about establishing a
      more systematic, scalable, and transparent sequential design-planning process for
      medical-product safety-surveillance systems utilizing observational electronic
      health care databases. Creating such a framework could yield improvements over
      existing practices, such as designs with increased power to assess serious
      adverse events.

PMID- 27713906
TI  - The role of substance use motives in the associations between minority stressors
      and substance use problems among young men who have sex with men.
AB  - Young men who have sex with men (YMSM) report higher rates of substance use than
      their heterosexual peers and minority stress has been posited as a risk factor
      for substance use. The associations between specific types of minority stress and
      substance use have been inconsistent throughout the literature and few studies
      have examined mechanisms underlying these associations. Drawing on minority
      stress theory and the motivational model of alcohol use, we propose that one
      mechanism underlying these associations may be people's motivations for using
      substances, including using substances to cope with negative emotions and to
      enhance pleasure. The goals of the current study were: (1) to examine the
      associations among minority stressors, substance use motives, and substance use
      problems; and (2) to examine substance use motives as mediators of the
      associations between minority stressors and substance use problems. Baseline self
      report data were used from a cohort of 370 YMSM enrolled in a larger study of
      substance use and sexual behavior. Results indicated that using marijuana to cope
      mediated the association between victimization and marijuana use problems. Using
      other drugs to cope mediated the associations between victimization and drug use
      problems and between internalized stigma and drug use problems. Drinking to cope
      and to enhance pleasure mediated the association between internalized stigma and
      alcohol use problems. In sum, substance use motives, especially using substances
      to cope, act as mechanisms through which certain types of minority stress
      influence substance use problems among YMSM.

PMID- 27713907
TI  - Utility of electronic medical record for recruitment in clinical research: from
      rare to common disease.
AB  - BACKGROUND: Recruitment for clinical trials is a major challenge. Movement
      disorders, which do not have associated diagnostic laboratory tests, may be
      especially prone to inaccuracy in coding. Our objective was to evaluate the
      accuracy of diagnostic codes such as cervical dystonia (CD) and PD in an
      electronic medical record. METHODS: Retrospective chart review was performed to
      confirm the ICD-9 diagnoses of PD, CD and diabetes mellitus type 2 (DM-2), using
      published clinical diagnostic criteria (PD, CD) and hemoglobin A1c >= 6.5 (DM-2).
      RESULTS: 421 charts (n=129, n=142, n=150 for PD, CD and DM-2, respectively) were
      reviewed. The accuracy rate was different between all diseases examined with an
      overall p<0.001. In post hoc pairwise comparisons, the accuracy of DM-2 diagnosis
      by ICD-9 (96.6%) was greater than CD (88.0%) and both greater than PD (55.0%)
      (p<=0.003). CONCLUSIONS: Using an electronic medical record based screening of
      clinically diagnosed diseases such as CD may be more accurate than previously
      thought and may identify potential clinical trial participants even without
      confirmatory lab tests available.

PMID- 27713905
TI  - A Harmonized Data Quality Assessment Terminology and Framework for the Secondary
      Use of Electronic Health Record Data.
AB  - OBJECTIVE: Harmonized data quality (DQ) assessment terms, methods, and reporting
      practices can establish a common understanding of the strengths and limitations
      of electronic health record (EHR) data for operational analytics, quality
      improvement, and research. Existing published DQ terms were harmonized to a
      comprehensive unified terminology with definitions and examples and organized
      into a conceptual framework to support a common approach to defining whether EHR
      data is 'fit' for specific uses. MATERIALS AND METHODS: DQ publications,
      informatics and analytics experts, managers of established DQ programs, and
      operational manuals from several mature EHR-based research networks were reviewed
      to identify potential DQ terms and categories. Two face-to-face stakeholder
      meetings were used to vet an initial set of DQ terms and definitions that were
      grouped into an overall conceptual framework. Feedback received from data
      producers and users was used to construct a draft set of harmonized DQ terms and
      categories. Multiple rounds of iterative refinement resulted in a set of terms
      and organizing framework consisting of DQ categories, subcategories, terms,
      definitions, and examples. The harmonized terminology and logical framework's
      inclusiveness was evaluated against ten published DQ terminologies. RESULTS:
      Existing DQ terms were harmonized and organized into a framework by defining
      three DQ categories: (1) Conformance (2) Completeness and (3) Plausibility and
      two DQ assessment contexts: (1) Verification and (2) Validation. Conformance and
      Plausibility categories were further divided into subcategories. Each category
      and subcategory was defined with respect to whether the data may be verified with
      organizational data, or validated against an accepted gold standard, depending on
      proposed context and uses. The coverage of the harmonized DQ terminology was
      validated by successfully aligning to multiple published DQ terminologies.
      DISCUSSION: Existing DQ concepts, community input, and expert review informed the
      development of a distinct set of terms, organized into categories and
      subcategories. The resulting DQ terms successfully encompassed a wide range of
      disparate DQ terminologies. Operational definitions were developed to provide
      guidance for implementing DQ assessment procedures. The resulting structure is an
      inclusive DQ framework for standardizing DQ assessment and reporting. While our
      analysis focused on the DQ issues often found in EHR data, the new terminology
      may be applicable to a wide range of electronic health data such as
      administrative, research, and patient-reported data. CONCLUSION: A consistent,
      common DQ terminology, organized into a logical framework, is an initial step in
      enabling data owners and users, patients, and policy makers to evaluate and
      communicate data quality findings in a well-defined manner with a shared
      vocabulary. Future work will leverage the framework and terminology to develop
      reusable data quality assessment and reporting methods.

PMID- 27713908
TI  - PPM1D/WIP1 in medulloblastoma.

PMID- 27713910
TI  - The anti-cancer components of Ganoderma lucidum possesses cardiovascular
      protective effect by regulating circular RNA expression.
AB  - To examine the role of oral Ganoderma spore oil in cardiovascular disease, we
      used transverse aortic constriction (TAC) in mice to model pressure overload
      induced cardiomyopathy. Our preliminary results demonstrated a potential
      cardioprotective role for spore oil extracted from Ganoderma. We found that
      Ganoderma treatment normalized ejection fraction and corrected the fractional
      shortening generated by TAC. We also found evidence of reduced left ventricular
      hypertrophy as assessed by left ventricular end diastolic diameter. Analysis of
      total RNA expression using cardiac tissue samples from these mice corroborated
      our findings. We found reduced expression of genes associated with heart failure,
      including a novel circular RNA circ-Foxo3. Thus our data provides evidence for
      Ganoderma lucidum as a potential cardioprotective agent, warranting further
      preclinical exploration.

PMID- 27713909
TI  - Selective glucocorticoid receptor-activating adjuvant therapy in cancer
      treatments.
AB  - Although adverse effects and glucocorticoid resistance cripple their chronic use,
      glucocorticoids form the mainstay therapy for acute and chronic inflammatory
      disorders, and play an important role in treatment protocols of both lymphoid
      malignancies and as adjuvant to stimulate therapy tolerability in various solid
      tumors. Glucocorticoid binding to their designate glucocorticoid receptor (GR),
      sets off a plethora of cell-specific events including therapeutically desirable
      effects, such as cell death, as well as undesirable effects, including
      chemotherapy resistance, systemic side effects and glucocorticoid resistance. In
      this context, selective GR agonists and modulators (SEGRAMs) with a more
      restricted GR activity profile have been developed, holding promise for further
      clinical development in anti-inflammatory and potentially in cancer therapies.
      Thus far, the research into the prospective benefits of selective GR modulators
      in cancer therapy limped behind. Our review discusses how selective GR agonists
      and modulators could improve the therapy regimens for lymphoid malignancies,
      prostate or breast cancer. We summarize our current knowledge and look forward to
      where the field should move to in the future. Altogether, our review clarifies
      novel therapeutic perspectives in cancer modulation via selective GR targeting.

PMID- 27713911
TI  - Weaponizing human EGF-containing fibulin-like extracellular matrix protein 1
      (EFEMP1) for 21st century cancer therapeutics.
AB  - De-regulated EFEMP1 gene expression in solid tumors has been widely reported with
      conflicting roles. We dissected EFEMP1 to identify domains responsible for its
      cell context-dependent dual functions, with the goal being to construct an EFEMP1
      derived tumor-suppressor protein (ETSP) that lacked tumor-promoting function.
      Exon/intron boundaries of EFEMP1 were used as boundaries of functional modules in
      constructing EFEMP1 variants, with removal of various module(s), and/or mutating
      an amino acid residue to convert a weak integrin binding-site into a strong one.
      A series of in vitro assays on cancerous features, and subcutaneous and
      intracranial xenograft-formation assays, were carried out for effects from
      overexpression of wild-type and variant forms of EFEMP1 in two glioma
      subpopulations characterized as tumor mass-forming cells (TMCs) or stem-like
      tumor initiating cells (STICs), where EFEMP1 showed cellcontext- dependent dual
      functions. One of the EFEMP1 variants was identified as the sought-after ETSP,
      which had a stronger tumor-suppression function in TMCs by targeting EGFR and
      angiogenesis, and a new tumor-suppression function in STICs by targeting NOTCH
      signaling and MMP2-mediated cell invasion. Therefore, ETSP may form the basis for
      further important research to develop a novel cancer therapy to treat many types
      of cancer by its tumor suppressor effect in the extracellular matrix compartment.

PMID- 27713912
TI  - Targeted proteomic approach in prostatic tissue: a panel of potential biomarkers
      for cancer detection.
AB  - Prostate cancer (PCa) is the sixth highest causes of cancer-related deaths in
      men. The molecular events underlying its behavior and evolution are not
      completely understood. Prostate-specific antigen (PSA) is the only approved Food
      and Drug Administration biomarker. A panel of ten stage-specific tumoral and
      adjacent non tumoral tissues from patients affected by PCa (Gleason score 6, 3+3;
      PSA 10 /19 ng/ml) was investigated by MS-based proteomics approach. The proposed
      method was based on identifying the base-soluble proteins from tissue,
      established an efficient study, which lead to a deeper molecular perspective
      understanding of the PCa. A total of 164 proteins were found and 132 of these
      were evaluated differentially expressed in tumoral tissues. The Ingenuity Pathway
      Analysis (IPA) showed that among all dataset obtained, 105 molecules were
      involved in epithelial neoplasia with a p-value of 3.62E-05, whereas, only 11
      molecules detected were ascribed to sentinel tissue and bodily fluids.

PMID- 27713913
TI  - The metastasis inducer CCN1 (CYR61) activates the fatty acid synthase (FASN)
      driven lipogenic phenotype in breast cancer cells.
AB  - The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated
      in metastatic breast carcinomas. However, little is known about the precise
      mechanisms that underlie the pro-metastatic actions of CCN1. Here, we
      investigated the impact of CCN1 expression on fatty acid synthase (FASN), a
      metabolic oncogene thought to provide cancer cells with proliferative and
      survival advantages. Forced expression of CCN1 in MCF-7 cells robustly up
      regulated FASN protein expression and also significantly increased FASN gene
      promoter activity 2- to 3-fold, whereas deletion of the sterol response element
      binding protein (SREBP) binding site in the FASN promoter completely abrogated
      CCN1-driven transcriptional activation. Pharmacological blockade of MAPK or PI
      3'K activation similarly prevented the ability of CCN1 to induce FASN gene
      activation. Pharmacological inhibition of FASN activity with the mycotoxin
      cerulenin or the small compound C75 reversed CCN1-induced acquisition of estrogen
      independence and resistance to hormone therapies such as tamoxifen and
      fulvestrant in anchorage-independent growth assays. This study uncovers
      FASNdependent endogenous lipogenesis as a new mechanism controlling the
      metastatic phenotype promoted by CCN1. Because estrogen independence and
      progression to a metastatic phenotype are hallmarks of therapeutic resistance and
      mortality in breast cancer, this previously unrecognized CCN1-driven lipogenic
      phenotype represents a novel metabolic target to clinically manage metastatic
      disease progression.

PMID- 27713915
TI  - A Closed-loop Brain Computer Interface to a Virtual Reality Avatar: Gait
      Adaptation to Visual Kinematic Perturbations.
AB  - The control of human bipedal locomotion is of great interest to the field of
      lower-body brain computer interfaces (BCIs) for rehabilitation of gait. While the
      feasibility of a closed-loop BCI system for the control of a lower body
      exoskeleton has been recently shown, multi-day closed-loop neural decoding of
      human gait in a virtual reality (BCI-VR) environment has yet to be demonstrated.
      In this study, we propose a real-time closed-loop BCI that decodes lower limb
      joint angles from scalp electroencephalography (EEG) during treadmill walking to
      control the walking movements of a virtual avatar. Moreover, virtual kinematic
      perturbations resulting in asymmetric walking gait patterns of the avatar were
      also introduced to investigate gait adaptation using the closed-loop BCI-VR
      system over a period of eight days. Our results demonstrate the feasibility of
      using a closed-loop BCI to learn to control a walking avatar under normal and
      altered visuomotor perturbations, which involved cortical adaptations. These
      findings have implications for the development of BCI-VR systems for gait
      rehabilitation after stroke and for understanding cortical plasticity induced by
      a closed-loop BCI system.

PMID- 27713914
TI  - ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for
      astrocytic tumors.
AB  - Recurrence and progression to higher grade lesions are key biological events and
      characteristic behaviors in the evolution process of glioma. Malignant astrocytic
      tumors such as glioblastoma (GBM) are the most lethal intracranial tumors.
      However, the clinical practicability and significance of molecular parameters for
      the diagnostic and prognostic prediction of astrocytic tumors is still limited.
      In this study, we detected ATRX, IDH1-R132H and Ki-67 by immunohistochemistry and
      observed the association of IDH1-R132H with ATRX and Ki-67 expression. There was
      a strong association between ATRX loss and IDH1-R132H (p<0.0001). However, Ki-67
      high expression restricted in the tumors with IDH1-R132H negative (p=0.0129).
      Patients with IDH1-R132H positive or ATRX loss astrocytic tumors had a longer
      progressive- free survival (p<0.0001, p=0.0044, respectively). High Ki-67
      expression was associated with shorter PFS in patients with astrocytic tumors
      (p=0.002). Then we characterized three prognostic subgroups of astrocytic tumors
      (referred to as A1, A2 and A3). The new model demonstrated a remarkable
      separation of the progression interval in the three molecular subgroups and the
      distribution of patients' age in the A1-A2-A3 model was also significant
      different. This model will aid predicting the overall survival and progressive
      time of astrocytic tumors' patients.

PMID- 27713916
TI  - Microsurgically aided upper lip replantation - case report and literature review.
AB  - A case with a patient who suffered an upper lip amputation and a lower lip
      laceration due to dog bite is presented. The amputated segment was replanted
      using microsurgical technique. The operative technique and postoperative care is
      presented, as well as a review of the current literature on the subject.

PMID- 27713917
TI  - Complete DIEP flap survival following pedicle resection, 4 years after its
      transfer. Clinical evidence of autonomization.
AB  - We report a case of complete DIEP flap survival, following venous congestion due
      to the excision of a local recurrence with main pedicle, 4 years after its
      transfer for breast reconstruction.

PMID- 27713918
TI  - Data for spatial analysis of growth anomaly lesions on Montipora capitata coral
      colonies using 3D reconstruction techniques.
AB  - Ten annotated 3D reconstructions of Montipora capitata coral colonies contain
      x,y,z coordinates for all growth anomaly (GA) lesions affecting these corals. The
      3D reconstructions are available as Virtual Reality Modeling Language (VRML)
      files, and the GA lesions coordinates are in accompanying text files. The VRML
      models and GA lesion coordinates can be spatially analyzed using Matlab. Matlab
      scripts are provided for three spatial statistical procedures in order to assess
      clustering of the GA lesions across the coral colony surfaces in a 3D framework:
      Ripley's K, Moran's I, and the Kolmogorov-Smirnov test. Please see the research
      article, "Investigating the spatial distribution of Growth Anomalies affecting
      Montipora capitata corals in a 3-dimensional framework" (J.H.R. Burns, T.
      Alexandrov, E. Ovchinnikova, R.D. Gates, M. Takabayashi, 2016) [1], for further
      interpretation and discussion of the data.

PMID- 27713919
TI  - Experimental data on the properties of polymer-modified cement grouts using epoxy
      and acrylic resin emulsions.
AB  - The use of additives to improve the quality of cement grouts is crucial for civil
      engineering, especially in foundation construction. This article presents
      experimental data concerning the compressive strength, elastic modulus, bleeding
      and injectability of microfine cement grouts modified with epoxy and acrylic
      resin emulsions. Strength properties were obtained at different curing ages. For
      further analysis and detailed discussion of properties of polymer-modified cement
      grouts, see "Fundamental properties of epoxy resin-modified cement grouts" (C.A.
      Anagnostopoulos, G. Sapidis, E. Papastergiadis, 2016) [1].

PMID- 27713920
TI  - Nodular cutaneous amyloidosis effectively treated with intralesional
      methotrexate.

PMID- 27713921
TI  - Predicting later life health status and mortality using state-level socioeconomic
      characteristics in early life.
AB  - Studies extending across multiple life stages promote an understanding of factors
      influencing health across the life span. Existing work has largely focused on
      individual-level rather than area-level early life determinants of health. In
      this study, we linked multiple data sets to examine whether early life state
      level characteristics were predictive of health and mortality decades later. The
      sample included 143,755 U.S. employees, for whom work life claims and
      administrative data were linked with early life state-of-residence and mortality.
      We first created a "state health risk score" (SHRS) and "state mortality risk
      score" (SMRS) by modeling state-level contextual characteristics with health
      status and mortality in a randomly selected 30% of the sample (the "training
      set"). We then examined the association of these scores with objective health
      status and mortality in later life in the remaining 70% of the sample (the "test
      set") using multivariate linear and Cox regressions, respectively. The
      association between the SHRS and adult health status was beta=0.14 (95%CI: 0.084,
      0.20), while the hazard ratio for the SMRS was 0.96 (95%CI: 0.93, 1.00). The
      association between the SHRS and health was not statistically significant in
      older age groups at a p-level of 0.05, and there was a statistically
      significantly different association for health status among movers compared to
      stayers. This study uses a life course perspective and supports the idea of
      "sensitive periods" in early life that have enduring impacts on health. It adds
      to the literature examining populations in the U.S. where large linked data sets
      are infrequently available.

PMID- 27713922
TI  - Training to use EUS-FNA : It is time to give up the human hands-on approach?

PMID- 27713923
TI  - The miR-132/212 locus: a complex regulator of neuronal plasticity, gene
      expression and cognition.
AB  - The microRNA (miRNA) class of small (typically 22-24 nt) non-coding RNA affects a
      wide range of physiological processes in the mammalian central nervous system
      (CNS). By acting as potent regulators of mRNA translation and stability, miRNAs
      fine-tune the expression of a multitude of genes that play critical roles in
      complex cognitive processes, including learning and memory. Of note, within the
      CNS, miRNAs can be expressed in an inducible, and cell-type specific manner.
      Here, we provide a brief overview of the expression and functional effects of the
      miR-132/212 gene locus in forebrain circuits of the CNS, and then discuss a
      recent publication that explored the contributions of miR-132 and miR-212 to
      cognition and to transcriptome regulation. We also discuss mechanisms by which
      synaptic activity regulates miR-132/212 expression, how miR-132 and miR-212
      affect neuronal plasticity, and how the dysregulation of these two miRNAs could
      contribute to the development of cognitive impairments.

PMID- 27713925
TI  - Time scale bias in erosion rates of glaciated landscapes.
AB  - Deciphering erosion rates over geologic time is fundamental for understanding the
      interplay between climate, tectonic, and erosional processes. Existing techniques
      integrate erosion over different time scales, and direct comparison of such rates
      is routinely done in earth science. On the basis of a global compilation, we show
      that erosion rate estimates in glaciated landscapes may be affected by a
      systematic averaging bias that produces higher estimated erosion rates toward the
      present, which do not reflect straightforward changes in erosion rates through
      time. This trend can result from a heavy-tailed distribution of erosional
      hiatuses (that is, time periods where no or relatively slow erosion occurs). We
      argue that such a distribution can result from the intermittency of erosional
      processes in glaciated landscapes that are tightly coupled to climate variability
      from decadal to millennial time scales. In contrast, we find no evidence for a
      time scale bias in spatially averaged erosion rates of landscapes dominated by
      river incision. We discuss the implications of our findings in the context of the
      proposed coupling between climate and tectonics, and interpreting erosion rate
      estimates with different averaging time scales through geologic time.

PMID- 27713924
TI  - Empirical observations of the spawning migration of European eels: The long and
      dangerous road to the Sargasso Sea.
AB  - The spawning migration of the European eel (Anguilla anguilla L.) to the Sargasso
      Sea is one of the greatest animal migrations. However, the duration and route of
      the migration remain uncertain. Using fishery data from 20 rivers across Europe,
      we show that most eels begin their oceanic migration between August and December.
      We used electronic tagging techniques to map the oceanic migration from eels
      released from four regions in Europe. Of 707 eels tagged, we received 206 data
      sets. Many migrations ended soon after release because of predation events, but
      we were able to reconstruct in detail the migration routes of >80 eels. The route
      extended from western mainland Europe to the Azores region, more than 5000 km
      toward the Sargasso Sea. All eels exhibited diel vertical migrations, moving from
      deeper water during the day into shallower water at night. The range of migration
      speeds was 3 to 47 km day-1. Using data from larval surveys in the Sargasso Sea,
      we show that spawning likely begins in December and peaks in February.
      Synthesizing these results, we show that the timing of autumn escapement and the
      rate of migration are inconsistent with the century-long held assumption that
      eels spawn as a single reproductive cohort in the springtime following their
      escapement. Instead, we suggest that European eels adopt a mixed migratory
      strategy, with some individuals able to achieve a rapid migration, whereas others
      arrive only in time for the following spawning season. Our results have
      consequences for eel management.

PMID- 27713926
TI  - The social costs of nitrogen.
AB  - Despite growing recognition of the negative externalities associated with
      reactive nitrogen (N), the damage costs of N to air, water, and climate remain
      largely unquantified. We propose a comprehensive approach for estimating the
      social cost of nitrogen (SCN), defined as the present value of the monetary
      damages caused by an incremental increase in N. This framework advances N
      accounting by considering how each form of N causes damages at specific locations
      as it cascades through the environment. We apply the approach to an empirical
      example that estimates the SCN for N applied as fertilizer. We track impacts of N
      through its transformation into atmospheric and aquatic pools and estimate the
      distribution of associated costs to affected populations. Our results confirm
      that there is no uniform SCN. Instead, changes in N management will result in
      different N-related costs depending on where N moves and the location,
      vulnerability, and preferences of populations affected by N. For example, we
      found that the SCN per kilogram of N fertilizer applied in Minnesota ranges over
      several orders of magnitude, from less than $0.001/kg N to greater than $10/kg N,
      illustrating the importance of considering the site, the form of N, and end
      points of interest rather than assuming a uniform cost for damages. Our approach
      for estimating the SCN demonstrates the potential of integrated biophysical and
      economic models to illuminate the costs and benefits of N and inform more
      strategic and efficient N management.

PMID- 27713927
TI  - Relative impacts of mitigation, temperature, and precipitation on 21st-century
      megadrought risk in the American Southwest.
AB  - Megadroughts are comparable in severity to the worst droughts of the 20th century
      but are of much longer duration. A megadrought in the American Southwest would
      impose unprecedented stress on the limited water resources of the area, making it
      critical to evaluate future risks not only under different climate change
      mitigation scenarios but also for different aspects of regional hydroclimate. We
      find that changes in the mean hydroclimate state, rather than its variability,
      determine megadrought risk in the American Southwest. Estimates of megadrought
      probabilities based on precipitation alone tend to underestimate risk.
      Furthermore, business-as-usual emissions of greenhouse gases will drive regional
      warming and drying, regardless of large precipitation uncertainties. We find that
      regional temperature increases alone push megadrought risk above 70, 90, or 99%
      by the end of the century, even if precipitation increases moderately, does not
      change, or decreases, respectively. Although each possibility is supported by
      some climate model simulations, the latter is the most common outcome for the
      American Southwest in Coupled Model Intercomparison 5 generation models. An
      aggressive reduction in global greenhouse gas emissions cuts megadrought risks
      nearly in half.

PMID- 27713928
TI  - Quantum optical rotatory dispersion.
AB  - The phenomenon of molecular optical activity manifests itself as the rotation of
      the plane of linear polarization when light passes through chiral media.
      Measurements of optical activity and its wavelength dependence, that is, optical
      rotatory dispersion, can reveal information about intricate properties of
      molecules, such as the three-dimensional arrangement of atoms comprising a
      molecule. Given a limited probe power, quantum metrology offers the possibility
      of outperforming classical measurements. This has particular appeal when samples
      may be damaged by high power, which is a potential concern for chiroptical
      studies. We present the first experiment in which multiwavelength polarization
      entangled photon pairs are used to measure the optical activity and optical
      rotatory dispersion exhibited by a solution of chiral molecules. Our work paves
      the way for quantum-enhanced measurements of chirality, with potential
      applications in chemistry, biology, materials science, and the pharmaceutical
      industry. The scheme that we use for probing wavelength dependence not only
      allows one to surpass the information extracted per photon in a classical
      measurement but also can be used for more general differential measurements.

PMID- 27713930
TI  - Intracellular pH-Induced Tip-to-Tip Assembly of Gold Nanorods for Enhanced
      Plasmonic Photothermal Therapy.
AB  - The search for efficient plasmonic photothermal therapies using nonharmful pulse
      laser irradiation at the near-infrared (NIR) is fundamental for biomedical cancer
      research. Therefore, the development of novel assembled plasmonic gold
      nanostructures with the aim of reducing the applied laser power density to a
      minimum through hot-spot-mediated cell photothermolysis is an ongoing challenge.
      We demonstrate that gold nanorods (Au NRs) functionalized at their tips with a pH
      sensitive ligand assemble into oligomers within cell lysosomes through hydrogen
      bonding attractive interactions. The unique intracellular features of the
      plasmonic oligomers allow us to significantly reduce the femtosecond laser power
      density and Au NR dose while still achieving excellent cell killing rates. The
      formation of gold tip-to-tip oligomers with longitudinal localized surface
      plasmon resonance bands at the NIR, obtained from low-aspect-ratio Au NRs close
      in resonance with 800 nm Ti:sapphire 90 fs laser pulses, was found to be the key
      parameter for realizing the enhanced plasmonic photothermal therapy.

PMID- 27713929
TI  - Intrinsic Functional Connectivity in Attention-Deficit/Hyperactivity Disorder: A
      Science in Development.
AB  - Functional magnetic resonance imaging (fMRI) without an explicit task, i.e.,
      resting state fMRI, of individuals with Attention-Deficit/Hyperactivity Disorder
      (ADHD) is growing rapidly. Early studies were unaware of the vulnerability of
      this method to even minor degrees of head motion, a major concern in the field.
      Recent efforts are implementing various strategies to address this source of
      artifact along with a growing set of analytical tools. Availability of the ADHD
      200 Consortium dataset, a large-scale multi-site repository, is facilitating
      increasingly sophisticated approaches. In parallel, investigators are beginning
      to explicitly test the replicability of published findings. In this narrative
      review, we sketch out broad, overarching hypotheses being entertained while
      noting methodological uncertainties. Current hypotheses implicate the interplay
      of default, cognitive control (frontoparietal) and attention (dorsal, ventral,
      salience) networks in ADHD; functional connectivities of reward-related and
      amygdala-related circuits are also supported as substrates for dimensional
      aspects of ADHD. Before these can be further specified and definitively tested,
      we assert the field must take on the challenge of mapping the "topography" of the
      analytical space, i.e., determining the sensitivities of results to variations in
      acquisition, analysis, demographic and phenotypic parameters. Doing so with
      openly available datasets will provide the needed foundation for delineating
      typical and atypical developmental trajectories of brain structure and function
      in neurodevelopmental disorders including ADHD when applied to large-scale multi
      site prospective longitudinal studies such as the forthcoming Adolescent Brain
      Cognitive Development study.

PMID- 27713932
TI  - Label-Free Isothermal Amplification Assay for Specific and Highly Sensitive
      Colorimetric miRNA Detection.
AB  - We describe a new method for the detection of miRNA in biological samples. This
      technology is based on the isothermal nicking enzyme amplification reaction and
      subsequent hybridization of the amplification product with gold nanoparticles and
      magnetic microparticles (barcode system) to achieve naked-eye colorimetric
      detection. This platform was used to detect a specific miRNA (miRNA-10b)
      associated with breast cancer, and attomolar sensitivity was demonstrated. The
      assay was validated in cell culture lysates from breast cancer cells and in serum
      from a mouse model of breast cancer.

PMID- 27713931
TI  - Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV
      1 Reverse Transcriptase.
AB  - We report the results of a binding free energy-based virtual screening campaign
      of a library of 77 alpha-hydroxytropolone derivatives against the challenging
      RNase H active site of the reverse transcriptase (RT) enzyme of human
      immunodeficiency virus-1. Multiple protonation states, rotamer states, and
      binding modalities of each compound were individually evaluated. The work
      involved more than 300 individual absolute alchemical binding free energy
      parallel molecular dynamics calculations and over 1 million CPU hours on national
      computing clusters and a local campus computational grid. The thermodynamic and
      structural measures obtained in this work rationalize a series of characteristics
      of this system useful for guiding future synthetic and biochemical efforts. The
      free energy model identified key ligand-dependent entropic and conformational
      reorganization processes difficult to capture using standard docking and scoring
      approaches. Binding free energy-based optimization of the lead compounds emerging
      from the virtual screen has yielded four compounds with very favorable binding
      properties, which will be the subject of further experimental investigations.
      This work is one of the few reported applications of advanced-binding free energy
      models to large-scale virtual screening and optimization projects. It further
      demonstrates that, with suitable algorithms and automation, advanced-binding free
      energy models can have a useful role in early-stage drug-discovery programs.

PMID- 27713933
TI  - Conformational Changes in High-Density Lipoprotein Nanoparticles Induced by High
      Payloads of Paramagnetic Lipids.
AB  - High-density lipoprotein (HDL) nanoparticles doped with gadolinium lipids can be
      used as magnetic resonance imaging diagnostic agents for atherosclerosis. In this
      study, HDL nanoparticles with different molar fractions of gadolinium lipids (0 <
      xGd-lipids < 0.33) were prepared, and the MR relaxivity values (r1 and r2) for
      all compositions were measured. Both r1 and r2 parameters reached a maximal value
      at a molar fraction of approximately xGd-lipids = 0.2. Higher payloads of
      gadolinium did not significantly increase relaxivity values but induced changes
      in the structure of HDL, increasing the size of the particles from dH = 8.2 +/-
      1.6 to 51.7 +/- 7.3 nm. High payloads of gadolinium lipids trigger conformational
      changes in HDL, with potential effects on the in vivo behavior of the
      nanoparticles.

PMID- 27713936
TI  - The reactivity of platinum microelectrodes.
AB  - Despite the widespread application of ultramicroelectrodes (UMEs), the customary
      method of their electrochemical characterization via outer sphere redox probing
      has serious limitations. In this study we provide additional insights into this
      subject by measuring not only outer sphere redox couples, but also blank
      voltammetries and the reactivity towards various catalytic reactions of Pt UMEs.
      The data for the UMEs are compared to those for macroscale Pt electrodes that can
      be flame-annealed. Although the reactivity is similar for reactions that are
      rather insensitive to the surface structure (and/or composition), UMEs perform
      much worse for more surface sensitive catalytic reactions. This effect can be
      explained by the UMEs being contaminated much faster, though it remains to be
      established if the origin of this contamination lies in the preparation method or
      in the impurities in the (high-purity grade) chemicals used. Our study recommends
      that catalytic reactivity measurements on ultramicroelectrodes should always be
      accompanied by blank voltammetries and the results have to be interpreted
      extremely carefully.

PMID- 27713935
TI  - Structural regulation by a G-quadruplex ligand increases binding abilities of G
      quadruplex-forming aptamers.
AB  - We report that a G-quadruplex-specific compound induced structural changes in G
      quadruplex-forming DNA aptamers and stabilized the folded structures, making them
      suitable for targeted proteins and enhancing their binding properties.

PMID- 27713934
TI  - Bimetallic MOFs (H3O)x[Cu(MF6)(pyrazine)2].(4 - x)H2O (M = V4+, x = 0; M = Ga3+,
      x = 1): co-existence of ordered and disordered quantum spins in the V4+ system.
AB  - The title compounds are bimetallic MOFs containing [Cu(pyz)2]2+ square lattices
      linked by MF6n- octahedra. In each, only the Cu2+ spins exhibit long-range
      magnetic order below 3.5 K (M = V4+) and 2.6 K (M = Ga3+). The V4+ spins remain
      disordered down to 0.5 K.

PMID- 27713937
TI  - Direct synthesis of nitroaryl acetylenes from acetylenes and nitroarenes via
      oxidative nucleophilic substitution of hydrogen.
AB  - Acetylenic carbanions add to nitroarenes (dinitrobenzenes, nitropyridines, etc.)
      to form sigmaH-adducts that are subsequently oxidized by DDQ according to the
      oxidative nucleophilic substitution of hydrogen (ONSH) pathway to give nitroaryl
      acetylenes.

PMID- 27713938
TI  - Effects of extending the pi-conjugation of the acetylide ligand on the
      photophysics and reverse saturable absorption of Pt(ii) bipyridine bisacetylide
      complexes.
AB  - The synthesis and photophysics of four platinum(ii) bipyridine (bpy) bisacetylide
      complexes with different degrees of pi-conjugation and an electron-donating
      diphenylamino (NPh2) or electron-withdrawing benzothiazolyl (BTZ) terminal
      substituent on the acetylide ligands are reported. The UV-vis absorption spectra
      of these complexes are composed of intense ligand-localized 1pi,pi* transitions
      at 330-430 nm and broad, moderately strong ligand-to-ligand charge transfer/metal
      to-ligand charge transfer (1LLCT/1MLCT) transitions at 430-530 nm. All complexes
      are phosphorescent in solutions at room temperature and exhibit very broad and
      moderately strong triplet excited-state absorption in the visible to the NIR
      spectral region (425-800 nm). It is found that extending the pi-conjugation of
      the acetylide ligands via adding one or two more ethynylfluorenyl unit(s) to the
      acetylide ligand does not change the energies of the 1pi,pi* and 1LLCT/1MLCT
      transitions pronouncedly except for increasing the molar extinction coefficients
      of the 1pi,pi* transitions. The emitting triplet excited states of the four
      complexes are the 3MLCT/3LLCT states and have the same energy. However, the
      complex that contains the tris(ethynylfluorenyl) units and the terminal NPh2
      substituent on the acetylide ligand exhibits longer triplet lifetimes than the
      corresponding complex that has the bis(ethynylfluorenyl) units. The transient
      absorption band maxima of the complexes with tris(ethynylfluorenyl) units are
      slightly red-shifted in comparison to those of their respective counterparts with
      bis(ethynylfluorenyl) units. The nature of the terminal substituent does not
      influence the parentage and energies of the lowest singlet and triplet excited
      states. However, the triplet excited-state lifetimes of the complexes with the
      NPh2 terminal substituent on the bis(ethynylfluorenyl) or tris(ethynylfluorenyl)
      ligands are much longer than that of their counterpart with
      monofluorenylacetylide ligands; while the triplet lifetimes of the complexes
      containing the BTZ terminal substituent are similar to their counterpart with
      monofluorenylacetylide ligands. All complexes exhibit strong reverse saturable
      absorption (RSA) at 532 nm for nanosecond laser pulses.

PMID- 27713940
TI  - Spin crossover and reversible single-crystal to single-crystal transformation
      behaviour in two cyanide-bridged mixed-valence {FeFe} clusters.
AB  - The reactions of tricyanometallate precursors, (Ph3PMe)[(Tp4-Me)Fe(CN)3.0.5CH3CN]
      (1) (Tp4-Me = tri(4-methyl-pyrazol-1-yl)borate) and (NBu4)[(MeTp)Fe(CN)3] (MeTp =
      methyltris(pyrazolyl)borate) with the presence of the tetradentate tpa ligand
      (tpa = tris(2-pyridylmethyl)amine) and Fe(ClO4)2.6H2O afford two new cyano
      bridged mixed-valence {FeFe} molecular squares: [(Tp4
      Me)FeIII(CN)3]2[FeII(tpa)]2.2ClO4.H2O (2.H2O) and
      [(MeTp)FeIII(CN)3]2[FeII(tpa)]2.2ClO4.CH3OH (3.CH3OH). Solvent-exchange compounds
      of 3.CH3OH, [(MeTp)FeIII(CN)3]2[FeII(tpa)]2.2ClO4.2H2O (3.2H2O), and their
      solvent-free form (2 and 3) are also obtained, respectively. The spin crossover
      (SCO) properties of all compounds are confirmed by detailed structural analyses
      of the coordination environments of the FeII centres and magnetic susceptibility
      measurements. All compounds exhibit SCO behaviour near room temperature (T1/2 =
      320 K for 2.H2O; 302 K for 2; 292 K for 3.CH3OH; 306 K for 3.2H2O and 290 K for
      3) and reversible single-crystal to single-crystal (SC-SC) transformations
      induced by guest desorption and resorption or solvent exchange. The transition
      temperature close to room temperature can be tuned by the dehydration and re
      hydration processes. The structure-property analysis discloses that the distorted
      {Fe4(MU-CN)4} core and deviations of bent ?Fe-N[triple bond, length as m-dash]C
      angles play a key role in tuning the transition temperature of these similar
      mixed-valence {FeFe} complexes.

PMID- 27713939
TI  - Novel tubulin-targeted cell penetrating antimitotic octapeptide.
AB  - An antimitotic cell penetrating octapeptide containing single Arg amino acid is
      discovered, which strongly binds with the exchangeable GTP/GDP binding site of
      tubulin, inhibits tubulin polymerization, reduces kinesin driven microtubule
      motility, activates apoptotic and mitotic check point proteins, induces apoptotic
      death and significantly inhibits the multicellular tumor spheroid growth of HeLa
      cells.

PMID- 27713942
TI  - Regioselective preparation of a bis-pyrazolinofullerene by a macrocyclization
      reaction.
AB  - A single isomer of a pyrazolinofullerene bis-adduct was prepared by tether
      directed remote functionalization. Specifically, a macrocyclization reaction
      between C60 and a bis-hydrazone reagent has been carried out to generate a
      regioisomerically pure fullerene bis-adduct which presents a lower LUMO than
      pristine C60.

PMID- 27713941
TI  - Neutral six-coordinate bis(dithiocarbamato)silicon(iv) complexes with an SiCl2S4
      skeleton.
AB  - Treatment of SiCl4 with lithium dithiocarbamates of the formula type Li[R2NCS2]
      (R = Ph, iPr) in a molar ratio of 1 : 2 afforded the respective six-coordinate
      silicon(iv) complexes [Ph2NCS2]2SiCl2 (3) and [iPr2NCS2]2SiCl2 (4), which were
      isolated as the solvates 3.MeCN and 4.MeCN. Compounds 3.MeCN and 4.MeCN were
      structurally characterised by single-crystal X-ray diffraction and multinuclear
      NMR spectroscopic studies in the solid state and in solution. In this study,
      dithiocarbamato ligands were implemented in silicon coordination chemistry for
      the first time. Compounds 3 and 4 represent the first six-coordinate silicon(iv)
      complexes with an SiCl2S4 skeleton.

PMID- 27713943
TI  - The influence of the dianhydride precursor in hyper-cross-linked hybrid polyPOSS
      imide networks.
AB  - Hybrid organic/inorganic hyper-cross-linked membranes based on imides covalently
      bonded with polyhedral oligomeric silsesquioxanes (POSS) have recently been
      developed for gas-separation applications under high pressure and/or temperature
      conditions. Their molecular sieving capabilities have been shown to depend on the
      nature of the organic dianhydride precursor. In the present work, realistic
      molecular models of such polyPOSS-imide films based on the flexible 6FDA
      dianhydride are compared to those based on the shorter and more rigid PMDA
      dianhydride. The models creation procedure closely mimicks the mixing,
      polycondensation and imidization steps of the experimental scheme. The resulting
      networks are found to be highly heterogeneous in terms of both the number of
      links (from zero to the maximum possible of eight per POSS cage with an average
      of four) and their structure (interPOSS, intraPOSS, single-links, double-links)
      because of the eight-equivalent-arms nature of the POSS precursor. For both
      dianhydride precursors, crosslinking with POSS and the subsequent imidization
      step decrease the density, create additional void-space and increase the
      solubility of the resulting membranes. However, when compared to PMDA, the added
      flexibility of the central 6FDA bridge leads to a larger thermally-induced
      dilation of the networks and a larger volume loss per H2O over the imidization
      step. With their better ability to redensify and to adapt to the added
      constraints, the cagecage distances and cage(organic bridge)cage angles in the
      6FDA polyPOSS-imides span a larger range than in their PMDA counterparts. In
      addition, the stiffness of the PMDA moiety results in more unrelaxed free volume
      remaining trapped in the PMDA polyPOSS-imides upon imidization, and as such, to
      significantly more open structures with less favourable interactions. As expected
      from their enhanced flexibility, the thermomechanical properties of the 6FDA
      networks are slightly lower than those based on PMDA. However, the better
      mechanical resistance of PMDA over 6FDA does not really become significant before
      very large volume dilations.

PMID- 27713944
TI  - Kramers' theory for diffusion on a periodic potential.
AB  - Kramers' turnover theory, based on the dynamics of the collective unstable normal
      mode (also known as PGH theory), is extended to the motion of a particle on a
      periodic potential interacting bilinearly with a dissipative harmonic bath. This
      is achieved by considering the small parameter of the problem to be the deviation
      of the collective bath mode from its value along the reaction coordinate, defined
      by the unstable normal mode. With this change, the effective potential along the
      unstable normal mode remains periodic, albeit with a renormalized mass, or
      equivalently a renormalized lattice length. Using second order classical
      perturbation theory, this not only enables the derivation of the hopping rates
      and the diffusion coefficient, but also the derivation of finite barrier
      corrections to the theory. The analytical results are tested against numerical
      simulation data for a simple cosine potential, ohmic friction, and different
      reduced barrier heights.

PMID- 27713945
TI  - Piceatannol is superior to resveratrol in promoting neural stem cell
      differentiation into astrocytes.
AB  - Piceatannol (3,3',4',5-trans-tetrahydroxystilbene) is a polyphenolic compound
      abundant in the seeds of passion fruit (Passiflora edulis). Piceatannol is an
      analogue of resveratrol (3,4',5-trans-trihydroxystilbene) and shares the
      structural motif and biological activities such as activation of SIRT1. Several
      studies have shown that piceatannol is more potent than resveratrol. In this
      study, we examined the effects of piceatannol on neural stem cell differentiation
      into astrocytes compared with those of resveratrol. At a concentration of 2.5
      MUM, piceatannol promoted astrocyte differentiation, while resveratrol had no
      effect at this concentration. Furthermore, we found that oral administration of
      piceatannol increased the number of astrocytes in the brains of adult mice, while
      resveratrol administration showed no effects. These results suggest that
      piceatannol has a superior effect to resveratrol in promoting astrocyte
      differentiation.

PMID- 27713951
TI  - Rapid infrared mapping for highly accurate automated histology in Barrett's
      oesophagus.
AB  - Barrett's oesophagus (BE) is a premalignant condition that can progress to
      oesophageal adenocarcinoma. Endoscopic surveillance aims to identify potential
      progression at an early, treatable stage, but generates large numbers of tissue
      biopsies. Fourier transform infrared (FTIR) mapping was used to develop an
      automated histology tool for detection of BE and Barrett's neoplasia in tissue
      biopsies. 22 oesophageal tissue samples were collected from 19 patients.
      Contiguous frozen tissue sections were taken for pathology review and FTIR
      imaging. 45 mid-IR images were measured on an Agilent 620 FTIR microscope with an
      Agilent 670 spectrometer. Each image covering a 140 MUm * 140 MUm region was
      measured in 5 minutes, using a 1.1 MUm2 pixel size and 64 scans per pixel.
      Principal component fed linear discriminant analysis was used to build
      classification models based on spectral differences, which were then tested using
      leave-one-sample-out cross validation. Key biochemical differences were
      identified by their spectral signatures: high glycogen content was seen in normal
      squamous (NSQ) tissue, high glycoprotein content was observed in glandular BE
      tissue, and high DNA content in dysplasia/adenocarcinoma samples. Classification
      of normal squamous samples versus 'abnormal' samples (any stage of Barrett's) was
      performed with 100% sensitivity and specificity. Neoplastic Barrett's (dysplasia
      or adenocarcinoma) was identified with 95.6% sensitivity and 86.4% specificity.
      Highly accurate pathology classification can be achieved with FTIR measurement of
      frozen tissue sections in a clinically applicable timeframe.

PMID- 27713952
TI  - Prospects of enhancing dietary zinc bioavailability with food-derived zinc
      chelating peptides.
AB  - Zinc is an essential micronutrient that strongly influences human health and
      nutrition through its involvement in several biological processes. Zinc functions
      as structural and functional component of many transcription factors and enzymes
      that regulate cell growth, gene expression, and immune response, and its
      deficiency can lead to retarded growth and impaired immune functions. The
      physiological functions of zinc are dependent on its bioavailability in tissues,
      which in turn depends on intestinal absorption of dietary zinc. The presence of
      dietary fibre and phytates impedes intestinal zinc absorption, as they can form
      insoluble complexes with zinc, decreasing its bioavailability. Peptides derived
      from food proteins can enhance zinc absorption and bioavailability. Peptides that
      contain amino acid residues such as cysteine, histidine, serine, aspartate and
      glutamate can chelate divalent metals, including zinc, forming soluble metal
      coordinate complexes. The structure-function relationship of zinc-chelating
      peptides and the stability of the peptide-metal complexes to gastrointestinal
      digestion are critical to their relevance in human nutrition and health
      promotion.

PMID- 27713953
TI  - Myricetin alleviates cuprizone-induced behavioral dysfunction and demyelination
      in mice by Nrf2 pathway.
AB  - Multiple sclerosis (MS) is a demyelinating disease occurring in the central
      nervous system. In the present study, we evaluated the function of myricetin on
      the alleviation of behavioral dysfunction and myelin protection in the cuprizone
      induced demyelination model. Mice were daily fed with fodder including 0.2%
      cuprizone and were administrated myricetin (100 mg kg-1) by gavage administration
      for 5 weeks. The treatment of myricetin ameliorated hyper-locomotion and behavior
      impairment induced by cuprizone toxicity. With the administration of myricetin,
      the demyelinating lesion was lessened via increasing the LFB staining area and
      myelin phosphatide protein (MBP) expression. In addition, myricetin evidently
      promoted Nrf2 translocation in the nuclear fraction and enhanced the HO-1 and
      NQO1 expression levels. Our data revealed that myricetin may be a potential
      candidate for mitigating motor defects and demyelination in a cuprizone-induced
      mouse model via activating the Nrf2 pathway.

PMID- 27713954
TI  - Anti-inflammatory activities of essential oil isolated from the calyx of Hibiscus
      sabdariffa L.
AB  - Hibiscus sabdariffa Linn., belonging to the family of Malvaceae, is considered to
      be a plant with health care applications in China. The main purpose of this study
      was to analyze the composition of its essential oil and assess its potential
      therapeutic effect on anti-inflammatory activity. A water steam distillation
      method was used to extract the essential oil from H. Sabdariffa. The essential
      oil components were determined by gas chromatography/mass spectrometry (GC-MS)
      analysis and a total of 18 volatile constituents were identified, the majority of
      which were fatty acids and ester compounds. Biological activity showed that the
      essential oil extracted from H. Sabdariffa exhibited excellent anti-inflammatory
      activity in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. The
      nitric oxide (NO) inhibition rate reached 67.46% when the concentration of the
      essential oil was 200 MUg mL-1. Further analysis showed that the anti
      inflammatory activity of the essential oil extracted from H. Sabdariffa might be
      exerted through inhibiting the activation of NF-kappaB and MAPK (JNK and ERK1/2)
      signaling pathways to decrease NO and pro-inflammatory cytokine (IL-1, IL-6, TNF
      alpha, COX-2, and iNOS) production. Thus, the essential oil extracted from H.
      Sabdariffa is a good source of a natural product with a beneficial effect against
      inflammation, and it may be applied as a food supplement and/or functional
      ingredient.

PMID- 27713955
TI  - Bolus matters: the influence of food oral breakdown on dynamic texture
      perception.
AB  - This review article focuses on design of food structure, characterisation of oral
      processing by boli characterisation and dynamic texture perception. Knowledge of
      the food properties governing bolus formation and bolus properties determining
      temporal changes in texture perception is of major importance. Such knowledge
      allows academia to better understand the mechanisms underlying texture perception
      and food industry to improve product texture. For instance, such knowledge can be
      used for developing foods with desired texture perception that fit in a healthy
      diet or that are customized to specific consumer groups. The end point of oral
      processing is the formation of a safe-to-swallow bolus. The transitions of solid
      and soft solid foods into bolus are accompanied by tremendous modifications of
      food properties. The review discusses dynamic changes in bolus properties
      resulting in dynamic changes of texture perception during oral processing.
      Studies monitoring chewing behaviour are discussed to complement the
      relationships between bolus properties and dynamic texture perception. We
      conclude that texture perception evolves over mastication time and depends on
      food properties, such as mechanical properties, mainly in the beginning of oral
      processing. Towards the middle and end of oral processing, bolus properties
      depend on food properties and explain texture perception better than food
      properties.

PMID- 27713956
TI  - Lipidomic approach in young adult triathletes: effect of supplementation with a
      polyphenols-rich juice on neuroprostane and F2-dihomo-isoprostane markers.
AB  - The aim of the this study was to determine the effect of a polyphenols-rich juice
      (aronia-citrus juice, ACJ) on F4-neuroprostanes and F2-dihomo-isoprostanes
      markers of oxidative stress associated with the central nervous system (CNS)-in
      16 elite triathletes under a controlled diet for triathlon training (145 days).
      In the triathletes, a decrease of the lipid peroxidation markers after ACJ
      intake, associated with neuronal membrane degradation (10-epi-10-F4t
      neuroprostane and 10-F4t-neuroprostane), was observed when compared with placebo
      stage values. Regarding the F2-dihomo-isoprostanes, a significant decrease of the
      neuromotor system damage biomarkers (17-F2t-dihomo-isoprostane) with an increase
      of training load during the study was observed, although the decrease of the load
      training at the last stage showed a significant increase of the values of ent-7
      (RS)-7-F2t-dihomo-IsoP, suggesting a possible role in adaptation post-training.
      On the other hand, the changes in the excretion of 17-epi-17-F2t-dihomo-IsoP
      provided a positive connection between physical exercise and ACJ intake. Thus,
      the results showed in this clinical study in young triathletes will help to
      elucidate novel interactions and mechanisms between the excretion of lipid
      peroxidation metabolites from CNS, supplementation of polyphenols-rich juice in
      the diet and physical exercise during a training season.

PMID- 27713957
TI  - Antidiabetic (type 2) effects of Lactobacillus G15 and Q14 in rats through
      regulation of intestinal permeability and microbiota.
AB  - The antidiabetic effects of Lactobacillus. paracasei subsp. paracasei G15 and
      Lactobacillus. casei Q14 in high fat diet and streptozotocin-induced type 2
      diabetic (T2D) rats were evaluated in this study. The strains were separated from
      Chinese traditional fermented dairy food. Administration of G15 and Q14 for 6
      weeks significantly improved the glucose tolerance and reduced the HbA1c levels
      in T2D rats. The probiotic treatment reduced the intestinal mucosal permeability
      and improved the epithelial barrier function through modification of the gut
      microbiota, which in turn lowered circulating LPS and inflammation cytokines,
      including IL-1beta and IL-8, and eventually alleviated the inflammatory status
      and islet beta-cell dysfunction. Combination of Q14 and metformin reversed the
      thymic atrophy and both G15 and Q14 lowered the circulating IL-6 level,
      indicating the immune-modulating potential of the strains. Lactobacillus.
      paracasei subsp. paracasei G15 and Lactobacillus. casei Q14 provide an insight
      into the biotherapy application of traditional fermented foods and their
      functional ingredients in the treatment of diabetes.

PMID- 27713958
TI  - Laminarin favorably modulates gut microbiota in mice fed a high-fat diet.
AB  - We investigated the anti-obesity effects of the potential prebiotic, laminarin,
      on mice fed a high-fat diet. A metagenomics approach was applied to characterize
      the ecological and functional differences of gut microbiota among mice fed a
      normal diet (CTL), a high-fat diet (HFD), and a laminarin-supplemented high-fat
      diet (HFL). The HFL mice showed a slower weight gain than the HFD mice during the
      laminarin-feeding period, but the rate of weight gain increased after the
      termination of laminarin supplementation. Gut microbial community analysis showed
      clear differences between the CTL and HFD mice, whereas the HFL mice were between
      the two. A higher abundance of carbohydrate active enzymes was observed in the
      HFL mice compared to the HFD mice, with especially notable increases in glycoside
      hydrolase and polysaccharide lyases. A significant decrease in Firmicutes and an
      increase in the Bacteroidetes phylum, especially the genus Bacteroides, were
      observed during laminarin ingestion. Laminarin ingestion altered the gut
      microbiota at the species level, which was re-shifted after termination of
      laminarin ingestion. Therefore, supplementing laminarin could reduce the adverse
      effects of a high-fat diet by shifting the gut microbiota towards a higher energy
      metabolism. Thus, laminarin could be used to develop anti-obesity functional
      foods. Our results also suggest that laminarin would need to be consumed
      regularly in order to prevent or manage obesity.

PMID- 27713959
TI  - A chitosan-coated liposome encapsulating antibacterial peptide, Apep10:
      characterisation, triggered-release effects and antilisterial activity in thaw
      water of frozen chicken.
AB  - Contamination of Listeria monocytogenes in food and their processing environment
      is a focus of attention in the food industry. To achieve the controlled release
      of antibacterial agents to a food processing environment contaminated by L.
      monocytogenes, chitosan-stabilised liposomes encapsulating Apep10 (GLARCLAGTL),
      an antibacterial peptide derived from boiled-dried anchovies, were prepared by
      utilising listeria toxins to activate the peptide release. Characteristics
      including the particle size, polydispersity index (PDI), encapsulation efficiency
      (EE), and morphology of the chitosan-coated Apep10 liposomes were investigated.
      The chitosan liposomes were more stable than their uncoated counterparts, which
      indicated that the coating of chitosan on the surface of the liposomes inhibited
      undesirable vesicle fusion and payload release during storage. However, once the
      chitosan-stabilised liposomes encountered L. monocytogenes, which secretes pore
      forming toxins, the encapsulated antibacterial peptide was released and it
      exerted antimicrobial effects on the strain. The results of time-kill inhibition,
      scanning electron microscopy (SEM), crystal violet staining and confocal laser
      scanning microscopy (CLSM) images demonstrated that these liposomes have
      favourable antibacterial and anti-biofilm activities against L. monocytogenes in
      the thaw water of frozen chicken. This bacterial toxin-enabled release of the
      encapsulated antibacterial peptide from chitosan-coated liposomes provides an
      effective approach for the control of listerial contamination. This technique can
      be broadly applied to treat contamination by a variety of pathogens that secrete
      pore-forming toxins.

PMID- 27713960
TI  - Hypouricemic effects of Mesona procumbens Hemsl. through modulating xanthine
      oxidase activity in vitro and in vivo.
AB  - Uric acid is a metabolite obtained from purine by xanthine oxidase activity (XO)
      and high levels of serum uric acid leads to hyperuricemia and gout. Mesona
      procumbens Hemsl. has been used as a healthy beverage and a traditional remedy.
      In this study, the hypouricemic effects of M. procumbens extracts were evaluated
      in vitro and in vivo. The 50% ethanol extract of M. procumbens (EE50) showed the
      strongest inhibitory effect on monosodium urate (MSU)-induced XO activity in THP
      1 cells. However, the phenolics and flavonoids in EE50 may not serve as
      inhibitors of XO. EE50 prevented an increase in the serum uric acid level in
      potassium oxonate (PO)-challenged ICR mice and streptozocin (STZ)-induced SD
      rats. EE50 down-regulated STZ-induced liver XO activity, and it restored renal
      OAT1 and urate transporter expression. STZ-induced renal interleukin-1beta (IL
      1beta) and the tumor necrosis factor-alpha (TNF-alpha) level were inhibited by
      EE50 treatment. EE50 exhibits the hypouricemic effect via down-regulation of XO
      activity, suggesting that EE50 has potential to improve hyperuricemia and its
      complications.

PMID- 27713961
TI  - Anti-cancer properties of olive oil secoiridoid phenols: a systematic review of
      in vivo studies.
AB  - Epidemiological studies suggest that olive oil intake is associated to a reduced
      risk of cancer. Recently, the chemopreventive activity of olive oil has been
      attributed to its unique phenolic compounds represented by phenolic alcohols,
      hydroxytyrosol (3,4-dihydroxyphenylethanol: 3,4-DHPEA) and tyrosol (p
      hydroxyphenylethanol: p-HPEA), and their secoiridoid derivatives 3,4-DHPEA-EA
      (oleuropein aglycon), p-HPEA-EA (ligstroside aglycon), 3,4-DHPEA-EDA, p-HPEA-EDA
      (oleocanthal), and oleuropein. Several studies have demonstrated that these
      compounds are able to inhibit proliferation and induce apoptosis in different
      tumor cell lines. These in vitro effects have been recently summarized in several
      reviews. The aim of this systematic review was to evaluate the in vivo anti
      cancer activities of secoiridoid phenols as evidenced by either animal models of
      carcinogenesis or human intervention trials. From the literature research through
      "PubMed" and "Web of Science", 16 animal studies and 5 human intervention trials
      were identified and included in the review. Most of the animal studies have
      confirmed the ability of these compounds to inhibit the carcinogenesis process at
      both initiation and promotion/progression phases. All human intervention trials
      have investigated the effects of olive oil phenols on DNA damage. Among the five
      selected studies, three have shown a significant preventive effect on oxidative
      DNA damage in terms of reduction of 8-oxo-7,8-dihydro-2'-deoxyguanosine in urine,
      in mitochondria DNA of mononuclear cells and in lymphocyte DNA. The other two
      studies failed to see an effect on the urinary excretion of either etheno-DNA
      adducts or oxidation products of guanine. Further investigations are necessary to
      clarify the real chemopreventive potential of olive oil secoiridoid phenols on
      humans performing intervention studies on populations at high cancer risk.

PMID- 27713962
TI  - Dietary supplement based on stilbenes: a focus on gut microbial metabolism by the
      in vitro simulator M-SHIME(r).
AB  - Polyphenols and intestinal microbiota can influence each other, modifying
      metabolism and gut wellness. Data on this mutual effect need to be improved.
      Several studies on the biological activities of resveratrol and derivatives have
      been carried out, but the effects of a continuous administration of stilbenes on
      gut microbiota have not yet been investigated. This study evaluated the effects
      of an extract from Vitis vinifera, containing a combination of t-resveratrol and
      epsilon-viniferin, on intestinal microbiota, using the advanced gastrointestinal
      simulator M-SHIME(r). A triple M-SHIME(r) experiment was performed using two
      concentrations of the extract (i.e. 1 and 2 g L-1), simulating a continuous daily
      intake. The effects were evaluated in terms of microbial functionality (SCFA and
      NH4+) and composition (DGGE and Illumina sequencing), since the microbiological
      aspect has been less considered so far. The treatment induced changes in
      microbial functionality and composition. In fact, the levels of SCFA and NH4+
      suffered a strong decrease (i.e. inhibition of the saccharolytic and proteolytic
      activity), while DGGE and Illumina showed important modifications of the
      microbiota composition, associated with an imbalance of the colonic microbiota
      (i.e. increase in the relative abundance of Enterobacteriaceae). HPLC-DAD-TOF-MS
      analyses demonstrated that the metabolism of t-resveratrol and other stilbenes
      was inhibited by continuous administration. Our results suggest M-SHIME(r) as an
      explorative tool to define the dosage of food supplements, in particular to
      simulate effective continuous administration in humans.

PMID- 27713963
TI  - delta and gamma tocotrienols suppress human hepatocellular carcinoma cell
      proliferation via regulation of Ras-Raf-MEK-ERK pathway-associated upstream
      signaling.
AB  - Tocotrienol (T3) has recently gained increasing interest due to its anti-cancer
      effect. Here, we investigated the modulating effect of delta and gamma T3 on the
      Ras-Raf-MEK-ERK oncogenic upstream signaling pathway in human hepatocellular
      carcinoma HepG2 cells. The results indicated that T3 regulated the upstream
      signaling cascades of this pathway.

PMID- 27713964
TI  - Effect of consumption of a carob pod inositol-enriched beverage on insulin
      sensitivity and inflammation in middle-aged prediabetic subjects.
AB  - This study assessed the effects of an inositol-enriched beverage (IEB) on blood
      glucose levels and inflammation status in subjects with an impaired fasting
      glucose (IFG) state according to body mass index (BMI). This was a 12 week,
      double-blind, randomized, controlled trial employing forty-four IFG subjects
      (fasting glucose levels 100-125 mg dl-1) that were divided into two intervention
      groups: one receiving a IEB (n = 24) containing mainly pinitol (2.0 g twice a
      day), and the other a sweetened beverage based on sucrose (SB; n = 20).
      Anthropometric and biochemical measurements, postprandial and fasting nocturnal
      glycaemia (continuous glucose monitoring system), and inflammatory parameters (IL
      6 and TNF-alpha) were analyzed at baseline and after intervention according to
      BMI (non-obese: BMI < 30 kg m-2 or obese: BMI >= 30 kg m-2). Non-obese subjects
      who consumed IEB exhibited a significant decrease in insulin (-14.4%), HOMA-IR
      index (-15.1%) and percentage of glucose change after postprandial and fasting
      nocturnal periods (-10.0% and -10.3%, respectively) compared with the SB group (
      2.35% and 10.2%, respectively) although they did not show any change in
      inflammatory cytokine levels. By contrast, obese subjects who consumed IEB showed
      a smaller variation in glucose levels after nocturnal fasting (-4.34%) and a
      marked decrease in IL-6 and TNF-alpha (p < 0.05). These findings support that
      consumption of IEB in prediabetic subjects produces a response that is dependent
      on BMI, with a clear improvement of insulin resistance and postprandial and
      nocturnal glycemia in non-obese subjects and a marked anti-inflammatory response
      in obese subjects.

PMID- 27713966
TI  - Hydroxysafflor yellow A inhibits IL-1beta-induced release of IL-6, IL-8, and MMP
      1 via suppression of ERK, NF-kappaB and AP-1 signaling in SW982 human synovial
      cells.
AB  - Hydroxysafflor yellow A (HSYA), the main active ingredient in medical and edible
      dual purpose plant safflower, is reported to have multiple bioactivities. In the
      present study, the anti-inflammatory effects of HSYA and the underlying
      mechanisms were investigated in interleukin (IL)-1beta-induced SW982 human
      synovial cells. The cells were pretreated with HSYA at various concentrations
      (2.5, 10 and 40 MUM) followed by IL-1beta (10 ng mL-1) stimulation. HSYA
      significantly inhibited the expression of IL-6, IL-8 and matrix metalloproteinase
      (MMP)-1 in IL-1beta-stimulated SW982 cells. HSYA also inhibited the
      phosphorylation of extracellular signal-regulated kinase (ERK), p65 and c-Jun. It
      also suppressed the degradation of IkappaBalpha and blocked p65 translocation
      into the nucleus. These results indicate that the inhibitory effects of HSYA on
      IL-1beta-induced IL-6, IL-8 and MMP-1 release might be mediated via suppression
      of ERK, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1)
      signaling pathways. The present data support the potential role of HSYA as an
      effective therapeutic agent in osteoarthritis.

PMID- 27713967
TI  - Cell-cycle-dependent Ca2+ transients in human induced pluripotent stem cells
      revealed by a simultaneous imaging of cell nuclei and intracellular Ca2+ level.
AB  - Cell cycle phase and [Ca2+]i are key determinants of self-renewal and
      differentiation in pluripotent stem cells. However, little is known about their
      relationship in human pluripotent stem cells owing to the lack of an effective
      method. Here, we applied an imaging-based approach for evaluating the
      relationship between the cell cycle and Ca2+ transients in human induced
      pluripotent stem (iPS) cells. Ca imaging and DNA staining was simultaneously
      performed at the same site. Then, individual cells were recognized and the cell
      cycle phase was estimated from the image of nuclei. We found that 18 +/- 4% of
      human iPS cells exhibited spontaneous Ca2+ transients and their inter-transient
      interval was 119 +/- 19 s. Ca wave events were observed in 64% of the sample and
      the [Ca2+]i elevation propagated among 47 +/- 30 cells with a duration of 57 +/-
      22 s. With the imaging-based approach, we demonstrated that the ratio of cells
      exhibiting Ca2+ transients significantly decreased during cell cycle progression,
      suggesting that the relationship previously described in mouse cells holds true
      in the human context as well. These results suggest that our method is suitable
      for evaluating Ca2+ transients, the cell cycle phase, and their relationship with
      densely cultured cells.

PMID- 27713968
TI  - Food processing and structure impact the metabolizable energy of almonds.
AB  - The measured metabolizable energy (ME) of whole almonds has been shown to be less
      than predicted by Atwater factors. However, data are lacking on the effects of
      processing (roasting, chopping or grinding) on the ME of almonds. A 5-period
      randomized, crossover study in healthy individuals (n = 18) was conducted to
      measure the ME of different forms of almonds (42 g per day), as part of a
      controlled diet: whole, natural almonds; whole, roasted almonds; chopped almonds;
      almond butter; and control (0 g per day). After 9 days of adaptation to each
      diet, participants collected all urine and fecal samples for 9 days. Diets,
      urine, and feces were analyzed to determine ME. Fracture force and fracture
      properties of whole and chopped almonds were measured. Measured ME (kcal g-1) of
      whole natural almonds (4.42), whole roasted almonds (4.86), and chopped almonds
      (5.04) was significantly lower than predicted with Atwater factors (P < 0.001);
      ME of almond butter (6.53 kcal g-1) was similar to predicted (P = 0.08). The ME
      of whole roasted and chopped almonds was lower than almond butter (P < 0.0001).
      ME of whole natural almonds was lower than whole roasted almonds (P < 0.05). This
      may be due to lower hardness of whole roasted (298 +/- 1.3 N) compared to whole
      natural almonds (345 +/- 1.6 N) (P < 0.05), and to whole natural almonds
      fracturing into fewer, larger particles, thus inhibiting the release of lipids.
      Atwater factors overestimate the ME of whole (natural and roasted) and chopped
      almonds. The amount of calories absorbed from almonds is dependent on the form in
      which they are consumed.

PMID- 27713965
TI  - Dietary resistant starch type 4-derived butyrate attenuates nuclear factor-kappa
      B1 through modulation of histone H3 trimethylation at lysine 27.
AB  - Indigestible resistant starches (RS) are substrates for gut-microbial metabolism
      and have been shown to attenuate intestinal inflammation but the supporting
      evidence is inconsistent and lacks mechanistic explanation. We have recently
      reported dietary RS type 4 (RS4) induced improvements in immunometabolic
      functions in humans and a concomitant increase in butyrogenic gut-bacteria. Since
      inflammation is a key component in metabolic diseases, here we investigated the
      effects of RS4-derived butyrate on the epigenetic repression of pro-inflammatory
      genes in vivo and in vitro. RS4-fed mice, compared to the control-diet group, had
      higher cecal butyrate and increased tri-methylation of lysine 27 on histone 3
      (H3K27me3) in the promoter of nuclear factor-kappa-B1 (NFkappaB1) in the colon
      tissue. The H3K27me3-enrichment inversely correlated with the concentration
      dependent down-regulation of NFkappaB1 in sodium butyrate treated human colon
      epithelial cells. Two additional inflammatory genes were attenuated by sodium
      butyrate, but were not linked with H3K27me3 changes. This exploratory study
      presents a new opportunity for studying underlying H3K27me3 and other methylation
      modifying mechanisms linked to RS4 biological activity.

PMID- 27713969
TI  - Effect of Bactrocera oleae on phenolic compounds and antioxidant and
      antibacterial activities of two Algerian olive cultivars.
AB  - Bactrocera oleae, an olive fruit fly, is a major olive pest in Algeria. In this
      study, olives of two Algerian cultivars (Limli and Rougette de Metidja) with
      different degrees of infestation by the Bactrocera oleae fly (0%, not attacked;
      100%, all attacked; and real %) were analysed. The influence of this pest on
      individual phenolic compounds (HPLC-DAD-FLD) and antioxidant profiles was
      ascertained. The antibacterial activity against 8 human enteropathogenic bacteria
      was also assessed. The results show that Rougette de Metidja, the cultivar with
      higher drupe size, was attacked to a greater degree than Limli, and the B. oleae
      attack caused a significant decrease in the total phenolic contents (>50%),
      including oleuropein, verbascoside, luteolin-7-O-glucoside, tyrosol and
      hydroxytyrosol. The antioxidant and antibacterial activities were highly
      correlated with the phenolic levels. Extracts from healthy olives were more
      effective against bacteria than those obtained from attacked olives. Globally,
      olive fly affected significantly the phenolic compounds of olives and their
      biological properties.

PMID- 27713970
TI  - Actomyosin contractility and RhoGTPases affect cell-polarity and directional
      migration during haptotaxis.
AB  - Although much is known about chemotaxis- induced by gradients of soluble chemical
      cues - the molecular mechanisms involved in haptotaxis (migration induced by
      substrate-bound protein gradients) are largely unknown. We used micropatterning
      to produce discontinuous gradients consisting of MUm-sized fibronectin-dots
      arranged at constant lateral but continuously decreasing axial spacing.
      Parameters like gradient slope, protein concentration and size or shape of the
      fibronectin dots were modified to determine optimal conditions for directional
      cell migration in gradient patterns. We demonstrate that fibroblasts
      predominantly migrate uphill towards a higher fibronectin density in gradients
      with a dot size of 2 * 2 MUm, a 2% and 6% slope, and a low fibronectin
      concentration of 1 MUg ml-1. Increasing dot size to 3.5 * 3.5 MUm resulted in
      stationary cells, whereas rectangular dots (2 * 3 MUm) orientated perpendicular
      to the gradient axis preferentially induce lateral migration. During haptotaxis,
      the Golgi apparatus reorients to a posterior position between the nucleus and the
      trailing edge. Using pharmacological inhibitors, we demonstrate that actomyosin
      contractility and microtubule dynamics are a prerequisite for gradient
      recognition indicating that asymmetric intracellular forces are necessary to read
      the axis of adhesive gradients. In the haptotaxis signalling cascade, RhoA and
      Cdc42, and the atypical protein kinase C zeta (aPKCzeta), but not Rac, are
      located upstream of actomyosin contractility.

PMID- 27713971
TI  - Template-assisted extrusion of biopolymer nanofibers under physiological
      conditions.
AB  - Biomedical applications ranging from tissue engineering to drug delivery systems
      require versatile biomaterials based on the scalable and tunable production of
      biopolymer nanofibers under physiological conditions. These requirements can be
      successfully met by a novel extrusion process through nanoporous aluminum oxide
      templates, which is presented in this study. With this simple method we are able
      to control the nanofiber diameter by chosing the size of the nanopores and the
      concentration of the biopolymer feed solution. Nanofiber assembly into different
      hierarchical fiber arrangements can be achieved with a wide variety of different
      proteins ranging from the intracellular proteins actin, alpha-actinin and myosin
      to the extracellular matrix components collagen, fibronectin, fibrinogen, elastin
      and laminin. The extrusion of nanofibers can even be applied to the
      polysaccharides hyaluronan, chitosan and chondroitin sulphate. Moreover, blends
      of different proteins or proteins and polysaccharides can be extruded into
      composite nanofibers. With these features our template-assisted extrusion process
      will lead to new avenues in the development of nanofibrous biomaterials.

PMID- 27713972
TI  - Vascular- and hepato-protective effects of passion fruit seed extract containing
      piceatannol in chronic high-fat diet-fed rats.
AB  - The effects of chronic administration of piceatannol-enriched (9.5% w/w) passion
      fruit seed extract (PFSE) on the cardiovascular damage induced in a high-fat (HF)
      diet-fed model of Fischer 344 rats were evaluated. Rats were fed the control, HF,
      or HF diets containing PFSE (0.5% w/w) for 16 weeks, and the effects of the
      various diets on the tissue weight, serum lipid profile, hepatic fibrosis,
      hepatic ductular reaction, cardiac function and aortic ring reactivity were
      examined. HF diet-fed rats developed signs of cardiovascular disease with
      abnormal serum profiles compared to control diet-fed rats. PFSE supplementation
      improved the liver hypertrophy and hepatic histology of the HF diet-fed rats. In
      addition, the triglyceride and cholesterol levels, platelet aggregation, cardiac
      function, and acetylcholine-mediated relaxation of the aortic ring were improved.
      These results suggest that the chronic intake of PFSE containing piceatannol
      prevents HF diet-induced cardiovascular disease in rats.

PMID- 27713973
TI  - Effects of enzyme activities during steeping and sprouting on the solubility and
      composition of proteins, their bioactivity and relationship with the bread making
      quality of wheat flour.
AB  - The aim was to determine the effect of steeping and sprouting on wheat grain
      proteins and the functional consequences in this regard. The solubility of
      proteins and the polypeptide composition of albumins, globulins, gliadins and
      glutenins were determined, as well as the content of non-protein nitrogen and
      free sulfhydryl groups (-SH), and the activity of peroxidase (POD) and
      lipoxygenase (LOX). In addition, the pasting viscosity of flour and protein
      bioactivity such as antioxidant capacity and immunoreactivity were evaluated. The
      increase of non-protein nitrogen and free -SH groups by about 62.09 and 96.7%,
      respectively, as well as the decrease of albumin + globulin polypeptides with a
      molecular weight over 85.94 kDa and between 85.94-48.00 kDa by about 34 and 8.7%,
      respectively, were the most notable changes observed in the flour from whole
      sprouted wheat that clearly point to the intensive protein hydrolysis. The
      reduction of disulfide bonds and increased concentrations of free -SH groups
      significantly modify the visco-elastic properties of gliadins and glutenins
      causing pasting viscosity reduction. However, sprouted wheat flour could be
      considered as a potential food ingredient because of its improved antioxidant
      capacity that is a result of protein hydrolysis inter alia. As protein
      modification induced by steeping may have beneficial effects on the antigenicity
      of the glutenin fraction, this kind of wheat pretreatment can represent a
      putative strategy in the dietary modulation of diseases related to glutenin
      immunoreactivity, e.g. dermatitis herpetiformis.

PMID- 27713974
TI  - The effect of sun-dried raisins (Vitis vinifera L.) on the in vitro composition
      of the gut microbiota.
AB  - Modulation of the human gut microbiota has proven to have beneficial effects on
      host health. The aim of this work was to evaluate the effect of sun-dried raisins
      (SR) on the composition of the human gut microbiota. A full model of the
      gastrointestinal tract, which includes simulated mastication, a dynamic gastric
      model, a duodenal model and a colonic model of the human large intestine, was
      used. An increase in the numbers of bifidobacteria and lactobacilli was observed
      by plate-counting in response to the addition of either SR or FOS after 8 and 24
      h fermentation. A significant decrease in Firmicutes and Bacteroidetes was
      observed in SR samples after 8 and 24 h fermentation. FOS resulted in the
      greatest production of short chain fatty acids. Sun-dried raisins demonstrated
      considerable potential to promote the colonization and proliferation of
      beneficial bacteria in the human large intestine and to stimulate the production
      of organic acids.

PMID- 27713976
TI  - Microfluidic partition with in situ biofabricated semipermeable biopolymer
      membranes for static gradient generation.
AB  - We report an in situ biofabrication strategy that conveniently partitions
      microfluidic networks into physically separated while chemically communicating
      microchannels with semipermeable biopolymer membranes, which enable the facile
      generation of static gradients for biomedical applications. The biofabrication of
      parallel biopolymer membranes was initiated with the dissipation of trapped air
      bubbles in parallel apertures in polydimethylsiloxane (PDMS) microfluidic
      devices, followed by tunable membrane growth with precise temporal and spatial
      control to the desired thickness. Static gradients were generated within minutes
      and well maintained over time by pure diffusion of molecules through the
      biofabricated semipermeable membranes. As an example application, the static
      gradient of alpha factor was generated to study the development of the "shmoo"
      morphology of yeast over time. The in situ biofabrication provides a simple
      approach to generate static gradients and an ideal platform for biological
      applications where flow-free static gradients are indispensable.

PMID- 27713977
TI  - Microfluidic technique for measuring wax appearance temperature of reservoir
      fluids.
AB  - A microfluidic technique for measuring wax appearance temperature (WAT) of
      reservoir fluids is presented. The technique is based on continuous monitoring of
      pressure across a microchannel as wax particles are deposited and gradually clog
      the channel. A rapid pressure increase was observed as the temperature was
      systematically decreased to wax appearance temperature. The relationship between
      pressure change rate and sample temperature is explored as the working principle
      in the proposed WAT measurement technique. This technique yields results which
      are comparable to measurements obtained from a cross-polar microscopy technique
      (CPM); the current industry-standard for WAT measurement. The method is validated
      by systematically investigating phase transition of pure hydrocarbons, binary
      mixtures, and real crude oils. The new technique has two distinct advantages over
      the existing industry standard methods in that its experimental setup is much
      simpler and it can be adapted to field applications. The microchannel can be
      easily cleaned and reused to test different samples.

PMID- 27713975
TI  - Modeling of the mechano-chemical behaviour of the nuclear pore complex: current
      research and perspectives.
AB  - Recent evidence suggests that mechanical deformation of the cell nucleus
      regulates the nuclear import of the transcriptional activators of genes involved
      in primary physiological cell responses such as stem cell differentiation. In
      addition, this nuclear mechanosensing response is de-regulated in pathological
      states, such as cancer and neurodegeneration. One hypothesis that could greatly
      advance the field is that the deformation of the nuclear envelope activates
      nuclear pore complexes through a direct mechanical link. The understanding of
      this possible mechanism for nuclear pore complex stretch-activation entails
      studying the mechanical connection of this complex to the nuclear envelope at the
      nanoscale. The nanomechanics of the nuclear pore complex is thus emerging as a
      novel research field, bridging nanoscience with nanotechnology. This review
      examines the frontier of research methodologies that are potentially useful for
      building a computational model of this interaction. This includes, for example,
      electron tomography to assess the geometrical features of the nuclear pore
      complex and nanoindentation to estimate its mechanical properties and that of the
      nuclear envelope. In order to summarize the state-of-the-art and perspectives in
      the field of NPC nanomechanics, this review covers highly interdisciplinary
      experimental and theoretical research methodologies pertaining to the fields of
      physics, chemistry, biology, materials and mechanics.

PMID- 27713978
TI  - Random design of microfluidics.
AB  - In this work we created functional microfluidic chips without actually designing
      them. We accomplished this by first generating a library of thousands of
      different random microfluidic chip designs, then simulating the behavior of each
      design on a computer using automated finite element analysis. The simulation
      results were then saved to a database which a user can query via to find chip
      designs suitable for a specific task. To demonstrate this functionality, we used
      our library to select chip designs that generate any three desired concentrations
      of a solute. We also fabricated and tested 16 chips from the library, confirmed
      that they function as predicted, and used these chips to perform a cell growth
      rate assay. This is one of many different applications for randomly-designed
      microfluidics; in principle, any microfluidic chip that can be simulated could be
      designed automatically using our method. Using this approach, individuals with no
      training in microfluidics can obtain custom chip designs for their own unique
      needs in just a few seconds.

PMID- 27713979
TI  - Magnetic separation of acoustically focused cancer cells from blood for
      magnetographic templating and analysis.
AB  - Liquid biopsies hold enormous promise for the next generation of medical
      diagnoses. At the forefront of this effort, many are seeking to capture,
      enumerate and analyze circulating tumor cells (CTCs) as a means to prognosticate
      and develop individualized treatments for cancer. Capturing these rare cells,
      however, represents a major engineering challenge due to their low abundance,
      morphology and heterogeneity. A variety of microfluidic tools have been developed
      to isolate CTCs from drawn blood samples; however, few of these approaches offer
      a means to separate and analyze cells in an integrated system. We have developed
      a microfluidic platform comprised of three modules that offers high throughput
      separation of cancer cells from blood and on-chip organization of those cells for
      streamlined analyses. The first module uses an acoustic standing wave to rapidly
      align cells in a contact-free manner. The second module then separates
      magnetically labeled cells from unlabeled cells, offering purities exceeding 85%
      for cells and 90% for binary mixtures of synthetic particles. Finally, the third
      module contains a spatially periodic array of microwells with underlying
      micromagnets to capture individual cells for on-chip analyses (e.g., staining,
      imaging and quantification). This array is capable of capturing with accuracies
      exceeding 80% for magnetically labeled cells and 95% for magnetic particles.
      Overall, by virtue of its holistic processing of complex biological samples, this
      system has promise for the isolation and evaluation of rare cancer cells and can
      be readily extended to address a variety of applications across single cell
      biology and immunology.

PMID- 27713980
TI  - Additively manufactured MEMS multiplexed coaxial electrospray sources for high
      throughput, uniform generation of core-shell microparticles.
AB  - This study reports the first MEMS multiplexed coaxial electrospray sources in the
      literature. Coaxial electrospraying is a microencapsulation technology based on
      electrohydrodynamic jetting of two immiscible liquids, which allows precise
      control with low size variation of the geometry of the core-shell particles it
      generates, which is of great importance in numerous biomedical and engineering
      applications, e.g., drug delivery and self-healing composites. By implementing
      monolithic planar arrays of miniaturized coaxial electrospray emitters that work
      uniformly in parallel, the throughput of the compound microdroplet source is
      greatly increased, making the microencapsulation technology compatible with low
      cost commercial applications. Miniaturized core-shell particle generators with up
      to 25 coaxial electrospray emitters (25 emitters cm-2) were fabricated via
      stereolithography, which is an additive manufacturing process that can create
      complex microfluidic devices at a small fraction of the cost per device and
      fabrication time associated with silicon-based counterparts. The characterization
      of devices with the same emitter structure but different array sizes demonstrates
      uniform array operation. Moreover, the data demonstrate that the per-emitter
      current is approximately proportional to the square root of the flow rate of the
      driving liquid, and it is independent of the flow rate of the driven liquid, as
      predicted by the theory. The core/shell diameters and the size distribution of
      the generated compound microparticles can be modulated by controlling the flow
      rates fed to the emitters.

PMID- 27713981
TI  - Field effect nanofluidics.
AB  - Nanoscale fluid transport through conduits in the 1-100 nm range is termed as
      nanofluidics. Over the past decade or so, significant scientific and
      technological advances have occurred in the domain of nanofluidics with a
      transverse external electrical signal through a dielectric layer permitting
      control over ionic and fluid flows in these nanoscale conduits. Consequently,
      this special class of nanofluidic devices is commonly referred to as field effect
      devices, analogous to the solid-state field effect transistors that form the
      basis for modern electronics. In this mini-review, we focus on summarizing the
      recent developments in field effect nanofluidics as a discipline and evaluate
      both tutorially and critically the scientific and technological advances that
      have been reported, including a discussion on the future outlook and identifying
      broad open questions which suggest that there are many breakthroughs still to
      come in field-effect nanofluidics.

PMID- 27713982
TI  - Smart hydrogels as storage elements with dispensing functionality in
      discontinuous microfluidic systems.
AB  - Smart hydrogels are useful elements in microfluidic systems because they respond
      to environmental stimuli and are capable of storing reagents. We present here a
      concept of using hydrogels (poly(N-isopropylacrylamide)) as an interface between
      continuous and discontinuous microfluidics. Their swelling and shrinking
      capabilities allow them to act as storage elements for reagents absorbed in the
      swelling process. When the swollen hydrogel collapses in an oil-filled channel,
      the incorporated water and molecules are expelled from the hydrogel and form a
      water reservoir. Water-in-oil droplets can be released from the reservoir
      generating different sized droplets depending on the flow regime at various oil
      flow rates (dispensing functionality). Different hydrogel sizes and microfluidic
      structures are discussed in terms of their storage and droplet formation
      capabilities. The time behaviour of the hydrogel element is investigated by
      dynamic swelling experiments and computational fluid dynamics simulations. By
      precise temperature control, the device acts as an active droplet generator and
      converts continuous to discontinuous flows.

PMID- 27713983
TI  - Scanning-SAXS of microfluidic flows: nanostructural mapping of soft matter.
AB  - The determination of in situ structural information of soft matter under flow is
      challenging, as it depends on many factors, such as temperature, concentration,
      confinement, channel geometry, and type of imposed flow. Here, we combine
      microfluidics and scanning small-angle X-ray scattering (scanning-SAXS) to create
      a two-dimensional spatially resolved map, which represents quantitatively the
      variation of molecular properties under flow. As application examples, mappings
      of confined amyloid fibrils and wormlike micelles under flow into various channel
      geometries are compared. A simple process to fabricate X-rays resistant chips,
      based on polyimide and UV-curing resin, is discussed. During experiments, these
      chips remained in high-energy synchrotron radiation for more than 24 hours,
      causing constant low background scattering. Thus, sufficient statistics were
      obtained from sample scattering at exposure times as low as 0.1 s, even with the
      small scattering volumes in microfluidic channels. Scanning-SAXS of microfluidic
      flows has many potential applications from biology to fundamental soft matter
      physics. In general, any fluid which has enough contrast for X-ray scattering can
      be measured to obtain the dependence of molecular shape, conformation, alignment
      and size on the flow field. Besides, dynamic processes of soft matter caused by
      flow, temperature, concentration gradient, and confinement, for example self
      assembling, aggregation, mixing, diffusion, and disintegration of macromolecules,
      can be quantified and visualized on a single image by this mapping technique.

PMID- 27713985
TI  - Fully automated chemiluminescence detection using an electrified-Lab-on-a-Disc
      (eLoaD) platform.
AB  - Typical Lab-on-a-Disc (LoaD) platforms cannot make a continuous measurement while
      the disc is spinning; this drawback means that the disc usually must be stopped
      and aligned with a sensor. This can result in measurement errors in time
      dependent assays along with inaccuracies due to liquid displacement and bubble
      formation in the absence of a stabilising centrifugal field. This paper presents
      a novel concept for a wirelessly electrified-Lab-on-a-Disc (eLoaD) platform that
      allows continuous measurement of experimental parameters while the disc is
      spinning. This platform incorporates all the components needed for measurement
      within the rotating frame of reference, and bidirectional transmission of data
      outside this reference frame, thus allowing for online measurement independent of
      the rotation of the disc. The eLoaD platform is conceived in a modular manner
      whereby an interchangeable and non-disposable 'Application Disc' can be fitted to
      the eLoaD platform and so the system can be adapted for a range of optical,
      electrochemical and other measurement types. As an application example, optical
      readout, using the Application Disc fitted with a silicon photomultiplier, is
      demonstrated using a tagged chemiluminescent antibody, which is commonly used,
      for instance, in ELISA assays. The precision of the eLoaD platform is >94%, while
      its accuracy, when compared to a commercial benchtop luminometer, is higher than
      96%. The modular design of this platform will permit extension of this technology
      to many other LoaD applications.

PMID- 27713984
TI  - Heracleum orphanidis: chemical characterisation, and comparative evaluation of
      antioxidant and antimicrobial activities with specific interest in the influence
      on Pseudomonas aeruginosa PAO1.
AB  - GC-FID and GC-MS were used to determine the chemical composition of the essential
      oil of the aerial parts of Heracleum orphanidis Boiss. Also, the HPLC-DAD/ESI-ToF
      MS profile of the methanol extracts of aerial parts and roots was determined. The
      main components of the essential oil were n-octanol, octyl hexanoate and n-octyl
      acetate, while coumarins were the most prevalent compounds in methanol extracts.
      An evaluation of antioxidant activity showed that the methanol and aqueous
      extracts of the aerial parts had the highest potential. In terms of antimicrobial
      activity determined by microdilution assays, the essential oil and methanol
      extract of the roots showed the greatest effectiveness. The colonies of
      Pseudomonas aeruginosa PAO1 treated with H. orphanidis samples produced less
      toxic pyocyanin, showed lower twitching and flagella mobility and biofilm
      formatting was reduced. The analyses in this study showed the considerable
      biological potential of H. orphanidis considering free radicals and various
      pathogenic strains, including the wild type of P. aeruginosa.

PMID- 27713986
TI  - Micro-/nanoscale electroporation.
AB  - Electroporation has been one of the most popular non-viral technologies for cell
      transfection. However, conventional bulk electroporation (BEP) shows significant
      limitations in efficiency, cell viability and transfection uniformity. Recent
      advances in microscale-electroporation (MEP) resulted in improved cell viability.
      Further miniaturization of the electroporation system (i.e., nanoscale) has
      brought up many unique advantages, including negligible cell damage and dosage
      control capabilities with single-cell resolution, which has enabled more
      translational applications. In this review, we give an insight into the
      fundamental and technical aspects of micro- and nanoscale/nanochannel
      electroporation (NEP) and go over several examples of MEP/NEP-based cutting-edge
      research, including gene editing, adoptive immunotherapy, and cellular
      reprogramming. The challenges and opportunities of advanced electroporation
      technologies are also discussed.

PMID- 27713988
TI  - Magnetic-adhesive based valves for microfluidic devices used in low-resource
      settings.
AB  - Since the introduction of micro total analytical systems (MUTASs), significant
      advances have been made toward development of lab-on-a-chip platforms capable of
      performing complex biological assays that can revolutionize public health, among
      other applications. However, use of these platforms in low-resource environments
      (e.g. developing countries) has yet to be realized as the majority of
      technologies used to control microfluidic flow rely on off-device hardware with
      non-negligible size, cost, power requirements and skill/training to operate. In
      this paper we describe a magnetic-adhesive based valve that is simple to
      construct and operate, and can be used to control fluid flow and store reagents
      within a microfluidic device. The design consists of a port connecting two
      chambers on different planes in the device that is closed by a neodymium disk
      magnet seated on a thin ring of adhesive. Bringing an external magnet into
      contact with the outer surface of the device unseats and displaces the valve
      magnet from the adhesive ring, exposing the port. Using this configuration, we
      demonstrate on-device reagent storage and on-demand transport and reaction of
      contents between chambers. This design requires no power or external
      instrumentation to operate, is extremely low cost ($0.20 materials cost per
      valve), can be used by individuals with no technical training, and requires only
      a hand-held magnet to actuate. Additionally, valve actuation does not compromise
      the integrity of the completely sealed microfluidic device, increasing safety for
      the operator when toxic or harmful substances are contained within. This valve
      concept has the potential to simplify design of MUTASs, facilitating development
      of lab-on-a-chip systems that may be practical for use in point-of-care and low
      resource settings.

PMID- 27713987
TI  - Rapid, portable and cost-effective yeast cell viability and concentration
      analysis using lensfree on-chip microscopy and machine learning.
AB  - Monitoring yeast cell viability and concentration is important in brewing, baking
      and biofuel production. However, existing methods of measuring viability and
      concentration are relatively bulky, tedious and expensive. Here we demonstrate a
      compact and cost-effective automatic yeast analysis platform (AYAP), which can
      rapidly measure cell concentration and viability. AYAP is based on digital in
      line holography and on-chip microscopy and rapidly images a large field-of-view
      of 22.5 mm2. This lens-free microscope weighs 70 g and utilizes a partially
      coherent illumination source and an opto-electronic image sensor chip. A touch
      screen user interface based on a tablet-PC is developed to reconstruct the
      holographic shadows captured by the image sensor chip and use a support vector
      machine (SVM) model to automatically classify live and dead cells in a yeast
      sample stained with methylene blue. In order to quantify its accuracy, we varied
      the viability and concentration of the cells and compared AYAP's performance with
      a fluorescence exclusion staining based gold-standard using regression analysis.
      The results agree very well with this gold-standard method and no significant
      difference was observed between the two methods within a concentration range of
      1.4 * 105 to 1.4 * 106 cells per mL, providing a dynamic range suitable for
      various applications. This lensfree computational imaging technology that is
      coupled with machine learning algorithms would be useful for cost-effective and
      rapid quantification of cell viability and density even in field and resource
      poor settings.

PMID- 27713989
TI  - Assessment of the prebiotic effect of quinoa and amaranth in the human intestinal
      ecosystem.
AB  - Quinoa and amaranth belong to the group of the so called "superfoods" and have a
      nutritional composition that confers multiple benefits. In this work, we explored
      the possibility of these foods exhibiting a prebiotic effect. These pseudocereals
      were subjected to an in vitro digestion and used as carbon sources in batch
      cultures with faecal human inocula. The effects on the microbiota composition and
      their metabolic products were determined by assessment of variations in pH, short
      chain fatty acid (SCFA) production and changes in the dynamic bacterial
      populations by fluorescence in situ hybridization (FISH). After 48 h of
      incubation, the total SCFAs were 106.5 mM for quinoa and 108.83 mM for amaranth,
      in line with the decrease in pH. Considerable differences (p < 0.05) were found
      in certain microbial groups, including Bifidobacterium spp., Lactobacillus
      Enterococcus, Atopobium, Bacteroides-Prevotella, Clostridium coccoides
      Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis. Our
      research suggests that these pseudocereals can have the prebiotic potential and
      that their intake may improve dysbiosis or maintain the gastrointestinal health
      through a balanced intestinal microbiota, although additional studies are
      necessary.

PMID- 27713990
TI  - Intake of cookies made with buriti oil (Mauritia flexuosa) improves vitamin A
      status and lipid profiles in young rats.
AB  - The oil extracted from Mauritia flexuosa (buriti) is rich in vitamin A,
      tocopherols and unsaturated fatty acids. This study evaluated the retinol status,
      blood glucose levels, lipid profiles, food efficiency rates (FERs), food
      conversion rates (FCRs) and murine anthropometric parameters of Wistar rats fed
      cookies made with buriti oil (BOC). The content of beta-carotene and
      monounsaturated fatty acids in the cookies was enhanced (p < 0.05) using buriti
      oil. Rats fed BOC showed an increase (p < 0.05) in serum and hepatic retinol
      levels compared to rats fed cookies made with soy oil (SOC - control). Rats fed
      BOC showed lower (p < 0.05) total and LDL cholesterol than the control; however,
      no changes in blood glucose levels or murine anthropometric parameters were
      observed. Serum retinol contents showed a strong correlation (r > 0.8) with
      hepatic retinol, and both groups of rats showed moderate correlations (r > 0.6 <
      0.5) with FERs, FCRs and weight gain. Taken together, these results indicated
      that buriti is an alternative to increase vitamin A in baked goods, particularly
      in cookies. Intake of BOC improves lipid profiles and retinol status without
      affecting blood glucose in young rats.

PMID- 27713991
TI  - CMOS biosensors for in vitro diagnosis - transducing mechanisms and applications.
AB  - Complementary metal oxide semiconductor (CMOS) technology enables low-cost and
      large-scale integration of transistors and physical sensing materials on tiny
      chips (e.g., <1 cm2), seamlessly combining the two key functions of biosensors:
      transducing and signal processing. Recent CMOS biosensors unified different
      transducing mechanisms (impedance, fluorescence, and nuclear spin) and readout
      electronics have demonstrated competitive sensitivity for in vitro diagnosis,
      such as detection of DNA (down to 10 aM), protein (down to 10 fM), or
      bacteria/cells (single cell). Herein, we detail the recent advances in CMOS
      biosensors, centering on their key principles, requisites, and applications.
      Together, these may contribute to the advancement of our healthcare system, which
      should be decentralized by broadly utilizing point-of-care diagnostic tools.

PMID- 27713992
TI  - In vitro bioaccessibility, transepithelial transport and antioxidant activity of
      Urtica dioica L. phenolic compounds in nettle based food products.
AB  - Nettle (Urtica dioica L.) is a well-known plant with a wide historical background
      use of stems, roots and leaves. Nettle leaves are an excellent source of phenolic
      compounds, principally 3-caffeoylquinic acid (3-CQA), caffeoylmalic acid (CMA)
      and rutin. The aim of this work was to evaluate the bioaccessibility (BAC), the
      bioavailability (BAV) and the antioxidant activity of nettle phenolic compounds
      present in foods and supplements. The BAC of nettle phenolics was evaluated with
      an in vitro dynamic digestion of real food matrices: the type of food matrix and
      chemical characteristic affected the kinetics of release and solubilization, with
      the highest BAC after duodenal digestion. A study of duodenal trans epithelial
      transport evidenced low bioavailability of native forms of 3-CQA, CMA and rutin.
      Simulation of colonic metabolism confirmed that phenolic compounds are fermented
      by gut microflora, confirming the need for further investigations on the impact
      of phenolic compounds at the large intestine level. Photochemiluminescence assay
      of the simulated digestion fluids demonstrated that ingestion of Urtica based
      foods contributes to create an antioxidant environment against superoxide anion
      radicals in the entire gastrointestinal tract (GIT).

PMID- 27713993
TI  - Polymerase chain reaction in microfluidic devices.
AB  - The invention of the polymerase chain reaction (PCR) has caused a revolution in
      molecular biology, giving access to a method of amplifying deoxyribonucleic acid
      (DNA) molecules across several orders of magnitude. Since the first application
      of PCR in a microfluidic device was developed in 1998, an increasing number of
      researchers have continued the development of microfluidic PCR systems. In this
      review, we introduce recent developments in microfluidic-based space and time
      domain devices as well as discuss various designs integrated with multiple
      functions for sample preparation and detection. The development of isothermal
      nucleic acid amplification and digital PCR microfluidic devices within the last
      five years is also highlighted. Furthermore, we introduce various commercial
      microfluidic PCR devices.

PMID- 27713995
TI  - Dynamics of bacterial streamers induced clogging in microfluidic devices.
AB  - Using a microfabricated porous media mimic platform, we investigated the clogging
      dynamics of bacterial biomass that accumulated in the device due to the formation
      of bacterial streamers. Particularly, we found the existence of a distinct
      clogging front which advanced via pronounced 'stick-slip' of the viscoelastic
      bacterial biomass over the solid surface of the micro pillar. Thus, the streamer,
      the solid surface, and the background fluidic media defined a clear three-phase
      front influencing these advancing dynamics. Interestingly, we also found that
      once the clogging became substantial, contrary to a static homogenous saturation
      state, the clogged mimic exhibited an instability phenomena marked by localized
      streamer breakage and failure leading to extended water channels throughout the
      mimic. These findings have implications for design and fabrication of biomedical
      devices and membrane-type systems such as porous balloon catheters, porous stents
      and filtration membranes prone to bacteria induced clogging as well as
      understanding bacterial growth and proliferation in natural porous media such as
      soil and rocks.

PMID- 27713994
TI  - Screw-actuated displacement micropumps for thermoplastic microfluidics.
AB  - The fabrication of on-chip displacement pumps integrated into thermoplastic chips
      is explored as a simple and low cost method for achieving precise and
      programmable flow control for disposable microfluidic systems. The displacement
      pumps consist of stainless steel screws inserted into threaded ports machined
      into a thermoplastic substrate which also serve as on-chip reagent storage
      reservoirs. Three different methods for pump sealing are investigated to enable
      high pressure flows without leakage, and software-defined control of multiple
      pumps is demonstrated in a self-contained platform using a compact and self
      contained microcontroller for operation. Using this system, flow rates ranging
      from 0.5-40 MUl min-1 are demonstrated. The pumps are combined with on-chip burst
      valves to fully seal multiple reagents into fabricated chips while providing on
      demand fluid distribution in a downstream microfluidic network, and demonstrated
      for the generation of size-tunable water-in-oil emulsions.

PMID- 27713996
TI  - Emergence of microfluidic wearable technologies.
AB  - There has been an intense interest in the development of wearable technologies,
      arising from increasing demands in the areas of fitness and healthcare. While
      still at an early stage, incorporating microfluidics in wearable technologies has
      enormous potential, especially in healthcare applications. For example, current
      microfluidic fabrication techniques can be innovatively modified to fabricate
      microstructures and incorporate electrically conductive elements on soft,
      flexible and stretchable materials. In fact, by leverarging on such
      microfabrication and liquid manipulation techniques, the developed flexible
      microfluidic wearable technologies have enabled several biosensing applications,
      including in situ sweat metabolites analysis, vital signs monitoring, and gait
      analysis. As such, we anticipate further significant breakthroughs and potential
      uses of wearable microfluidics in active drug delivery patches, soft robotics
      sensing and control, and even implantable artificial organs in the near future.

PMID- 27713998
TI  - Diagnosis of iron deficiency anemia using density-based fractionation of red
      blood cells.
AB  - Iron deficiency anemia (IDA) is a nutritional disorder that impacts over one
      billion people worldwide; it may cause permanent cognitive impairment in
      children, fatigue in adults, and suboptimal outcomes in pregnancy. IDA can be
      diagnosed by detection of red blood cells (RBCs) that are characteristically
      small (microcytic) and deficient in hemoglobin (hypochromic), typically by
      examining the results of a complete blood count performed by a hematology
      analyzer. These instruments are expensive, not portable, and require trained
      personnel; they are, therefore, unavailable in many low-resource settings. This
      paper describes a low-cost and rapid method to diagnose IDA using aqueous
      multiphase systems (AMPS)-thermodynamically stable mixtures of biocompatible
      polymers and salt that spontaneously form discrete layers having sharp steps in
      density. AMPS are preloaded into a microhematocrit tube and used with a drop of
      blood from a fingerstick. After only two minutes in a low-cost centrifuge, the
      tests (n = 152) were read by eye with a sensitivity of 84% (72-93%) and a
      specificity of 78% (68-86%), corresponding to an area under the curve (AUC) of
      0.89. The AMPS test outperforms diagnosis by hemoglobin alone (AUC = 0.73) and is
      comparable to methods used in clinics like reticulocyte hemoglobin concentration
      (AUC = 0.91). Standard machine learning tools were used to analyze images of the
      resulting tests captured by a standard desktop scanner to 1) slightly improve
      diagnosis of IDA-sensitivity of 90% (83-96%) and a specificity of 77% (64-87%),
      and 2) predict several important red blood cell parameters, such as mean
      corpuscular hemoglobin concentration. These results suggest that the use of AMPS
      combined with machine learning provides an approach to developing point-of-care
      hematology.

PMID- 27713997
TI  - Valve interstitial cell contractile strength and metabolic state are dependent on
      its shape.
AB  - The role of valvular interstitial cell (VIC) architecture in regulating cardiac
      valve function and pathology is not well understood. VICs are known to be more
      elongated in a hypertensive environment compared to those in a normotensive
      environment. We have previously reported that valve tissues cultured under
      hypertensive conditions are prone to acute pathological alterations in cell
      phenotype and contractility. We therefore aimed to rigorously study the
      relationship between VIC shape, contractile output and other functional
      indicators of VIC pathology. We developed an in vitro model to engineer VICs to
      take on the same shapes as those seen in normal and hypertensive conditions. VICs
      with longer cellular and nuclear shapes, as seen in hypertensive conditions, had
      greater contractile response to endothelin-1 that correlated with increased
      anisotropy of the actin architecture. These elongated VICs also demonstrated
      altered cell metabolism through a decreased optical redox ratio, which coincided
      with increased cellular proliferation. In the presence of actin polymerization
      inhibitor, however, these functional responses were significantly reduced,
      suggesting the important role of cytoskeletal actin organization in regulating
      cellular responses to abnormal shape. Overall, these results demonstrate the
      relationship between cell shape, cytoskeletal and nuclear organization, with
      functional output including contractility, metabolism, and proliferation.

PMID- 27713999
TI  - An LC-MS based untargeted metabolomics study identified novel biomarkers for
      coronary heart disease.
AB  - This study performed untargeted metabolomics for plasma samples from 40 coronary
      heart disease patients and 43 healthy controls by high-performance liquid
      chromatography coupled with mass spectrometry technology to find a set of
      effective biomarkers for CHD diagnosis and prognosis. The discriminating
      metabolites were extracted and analyzed by univariate and multivariate analysis
      methods. We found five metabolites (1-naphthol, 2-naphthol, methylitaconate, N
      acetyl-d-glucosamine 6-phosphate and l-carnitine) contributing to the separation
      of CHD patients from healthy controls, and a subset of two metabolites in these
      five were identified as potential plasma biomarkers for CHD diagnosis. Major
      metabolic pathways associated with these potential biomarkers included nicotinate
      and nicotinamide metabolism, protein glycosylation, lipid metabolism and fatty
      acid metabolism. In addition, two potential biomarkers (GlcNAc-6-P and l
      carnitine) were found be to be associated with intestinal microflora, indicating
      that intestinal microflora may be related to the metabolism and progression of
      CHD.

PMID- 27714000
TI  - Flow-induced phase inversion of emulsions in tapered microchannels.
AB  - Phase inversion emulsification (PIE) is a process of generating emulsions by
      inverting the continuous and dispersed phases of pre-existing emulsions. Although
      PIE is conventionally performed in batch processes, flowing emulsions through
      precisely engineered channels (i.e. flow-induced phase inversion emulsification
      (FIPIE)) can induce PIE and potentially enable continuous processing. In this
      study, we demonstrate flow-induced phase inversion of oil-in-water (O/W)
      emulsions using microfluidic channels with gradual constriction. We investigate
      the importance of wetting properties and geometric characteristics of
      microfluidic channels on FIPIE. We show that two dimensionless groups, Ca and the
      ratio of droplet-size to channel dimensions determine the outcome of the process.
      In situ observation of individual droplets undergoing FIPIE reveals that the
      rupture of films of the continuous (water) phase between oil droplets and a
      wetting oil layer on the surface of microchannels is the most crucial step for
      phase inversion. Finally, we compare our experimental observations with a scaling
      relationship that is based on the force balance between disjoining pressure and
      Laplace pressure, which provides insights into the underlying physical phenomena
      responsible for the rupture of the aqueous film and the occurrence of FIPIE. We
      believe our work provides critical insights and parameters for designing channels
      and pores that can be used for continuous PIE.

PMID- 27714001
TI  - Single-layer microfluidic device to realize hydrodynamic 3D flow focusing.
AB  - The recent rapid growth of microfluidic applications has witnessed the emergence
      of several particle flow focusing techniques for analysis and/or further
      processing. The majority of flow focusing techniques employ an external sheath
      fluid to achieve sample flow focusing independent of the flow rate, in contrast
      to sheath-free techniques. However, the introduction of a sheath fluid to
      surround the sample fluid has complicated the device design and fabrication,
      generally involving multi-layer fabrication and bonding of multiple
      polydimethylsiloxane (PDMS) layers. Several promising efforts have been made to
      reduce the complexity of fabrication. However, most of these methods involved the
      use of inertial/Dean effects, which in turn demanded the use of higher sample
      flow rates. In this paper, we report a method of flow focusing that uses a sheath
      fluid to enclose the sample in a single layer of PDMS, and that possesses
      applicability for a wide range of sample flow rates. This method of flow focusing
      uses abrupt channel depth variation and a shift of one of the sample-sheath
      junctions (termed as 'junction-shift') against the direction of the sample flow.
      This configuration serves to manipulate the sample fluid with respect to the
      sheath fluid and achieve the desired flow focusing. This design facilitates the
      attainment of 3D flow focusing in two sequential steps (depth-wise and then along
      the lateral direction) and in distinct regions, hence enabling the regions to be
      used in imaging and non-imaging flow cytometric applications, respectively.
      Simulations were performed to characterize and determine the optimum set of
      design parameters. Experimental demonstrations of this technique were carried out
      by focusing fluorescein dye and blood cells in flow.

PMID- 27714002
TI  - The effect of minimal dietary changes with raisins in NAFLD patients with non
      significant fibrosis: a randomized controlled intervention.
AB  - Aiming at investigating the potential effect of minimal dietary changes in NAFLD
      patients with non-significant fibrosis, 55 patients with NAFLD were enrolled in a
      randomized controlled clinical trial. Patients were assigned into two isocaloric
      dietary treatment groups for 24 weeks: (a) nutritional counseling (Control arm, N
      = 27), (b) nutritional counseling with currants included (two fruit servings, 36
      g per day), substituting snacks of similar caloric content (Currant arm, N = 28).
      Clinical tests, anthropometrics, inflammatory and oxidative stress markers were
      conducted pre- and post-intervention. A total of 50 patients completed the trial.
      Significant differences between the two arms post-intervention were observed in
      fasting glucose and in IL-6 levels, these being significantly decreased only in
      Currant patients. Body weight, BMI, HbA1c, CRP and EUS values decreased in both
      arms, differences being insignificant between the two arms post-intervention.
      Participants in the Currant arm had significantly reduced total body fat, WC and
      trunk fat. Ultrasound scanning improved significantly in patients snacking
      currants daily. Also, volunteers enrolled in the Currant arm showed a reduced
      intake of saturated fatty acids. Because BW regulation has been officially
      recognised as a treatment approach in NAFLD an additional analysis was repeated
      in patients adhering to this. Post-intervention, the decrease in IL-6 and in
      fasting glucose was significantly higher in Currant patients who lost BW compared
      to their counterparts in the Control arm. Conclusively, minimal modifications in
      snacking choices, such as the inclusion of dried grapes in diet, are beneficial
      in NAFLD patients with non-significant fibrosis.

PMID- 27714003
TI  - Heterotypic 3D tumor culture in a reusable platform using pneumatic
      microfluidics.
AB  - The construction of a micro-platform capable of microscale control for
      continuous, dynamic, and high-throughput biomimetic tumor manipulation and
      analysis plays a significant role in biological and clinical research. Here, we
      introduce a pneumatic microstructure-based microfluidic platform for versatile
      three-dimensional (3D) tumor cultures. The manipulative potential of pneumatic
      microstructures in a fabrication-optimized microfluidic device can be stimulated
      to achieve ultra-repetitive (tens of thousands of times) and persistent (over
      several months) microfluidic control. We demonstrated that the microfluidic
      platform is reusable (dozens of times) for stable, reproducible, and high
      throughput generation of tumors with uniform size. Various heterotypic and
      homotypic 3D tumor arrays can be produced successfully in the device based on
      robust pneumatic control. On-chip monitoring and analysis of tumor phenotypes and
      responses to different culture conditions and chemotherapies were also achieved
      in real-time in the microfluidic platform. The results indicate that fibroblasts
      cocultured with tumor cells positively promote the phenotypical appearance of
      heterotypic tumors. This microfluidic advancement offers a new methodological
      approach for the development of high-performance and non-disposable 3D culture
      systems and for tissue-mimicking cancer research. We believe that it could be
      valuable for various tumor-related research fields such as oncology,
      pharmacology, tissue engineering, and bioimaging.

PMID- 27714004
TI  - Yerba mate (Ilex paraguariensis) inhibits lymphocyte activation in vitro.
AB  - Yerba mate (YM) has been shown to have anti-inflammatory properties in several
      studies. However, this effect has been found mainly in obesity-related
      inflammation. The aim of this work was to study the effect of YM on cultured
      peripheral blood mononuclear cells to see whether it has anti-inflammatory
      properties. We stimulated peripheral blood mononuclear cells in vitro with
      phytohemagglutinin (PHA) in the presence of yerba mate and determined their
      activation by measuring the expression of CD25 by flow cytometry. We observed
      that YM treatment produced a dose-dependent reduction in PBMC activation (CD25
      positive cells) when they were stimulated with PHA. This effect was also observed
      in T cells' (CD3 positive) subpopulation. Microarray analysis revealed the
      differential expression of 128 genes in YM-treated cells. According to a protein
      protein interaction database, these genes were highly connected and they are
      involved in the inflammatory response. In summary, it was demonstrated that YM
      produces a reduction in the amount of activated cells under the stimulation of
      PHA. Therefore, it might be used in diseases with an inflammatory component.

PMID- 27714005
TI  - Polydatin attenuates d-galactose-induced liver and brain damage through its anti
      oxidative, anti-inflammatory and anti-apoptotic effects in mice.
AB  - Accumulating evidence has shown that chronic injection of d-galactose (d-gal) can
      mimic natural aging, with accompanying liver and brain injury. Oxidative stress
      and apoptosis play a vital role in the aging process. In this study, the
      antioxidant ability of polydatin (PD) was investigated using four established in
      vitro systems. An in vivo study was also conducted to investigate the possible
      protective effect of PD on d-gal-induced liver and brain damage. The results
      showed that PD had remarkable in vitro free radical scavenging activity on 2,2
      diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6
      sulfonic acid) (ABTS+) radical ions, and hydroxyl and superoxide anions. Results
      in vivo indicated that, in a group treated with d-gal plus PD, PD remarkably
      decreased the depression of body weight and organ indexes, reduced the levels of
      the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST),
      and alleviated alterations in liver and brain histopathology. PD also
      significantly decreased the level of MDA and elevated SOD, GSH-Px, CAT activity
      and T-AOC levels in the liver and brain. In addition, the levels of inflammatory
      mediators, such as TNF-alpha, IL-1beta and IL-6 in serum were markedly reduced
      after PD treatment. Western blotting results revealed that PD treatment
      noticeably attenuated the d-gal-induced elevation of Bcl-2/Bax ratio and caspase
      3 protein expression in liver and brain. Overall, our findings indicate that PD
      treatment could effectively attenuate d-gal-induced liver and brain damage, and
      the mechanism might be associated with decreasing the oxidative stress,
      inflammation and apoptosis caused by d-gal. PD holds good potential for further
      development into a promising pharmaceutical candidate for the treatment of age
      associated diseases.

PMID- 27714006
TI  - Microfluidics in microbiology: putting a magnifying glass on microbes.
AB  - Microfluidic technologies enable unique studies in the field of microbiology to
      facilitate our understanding of microorganisms. Using miniaturized and high
      throughput experimental capabilities in microfluidics, devices with controlled
      microenvironments can be created for microbial studies in research fields such as
      healthcare and green energy. In this research highlight, we describe recently
      developed tools for diagnostic assays, high-throughput mutant screening, and the
      study of human disease development as well as a future outlook on microbes for
      renewable energy.

PMID- 27714007
TI  - Multiple actuation microvalves in wax microfluidics.
AB  - Microvalves are an essential component of microfluidic devices. In this work, a
      low-consumption (<35 mJ), fast-response (<0.3 s), small footprint (<0.5 mm2) wax
      microvalve capable of multiple actuation is described. This phase-change
      microvalve is electrically controlled, simple to operate and can be easily
      fabricated as a fully integrated element of wax microfluidic devices through a
      special decal-transfer microlithographic process. The valve is inherently latched
      and leak-proof to at least 100 kPa. A minimum pressure of 3 kPa is required for
      valve opening. Maximum pressures for a successful closing in air and liquid are
      90 and 40 kPa, respectively. The wax valve exhibits reversible open-close
      behaviour without failure for up to 10 actuation cycles in air (60 kPa) and 5 in
      water (30 kPa). To the best of our knowledge, this microvalve has the lowest
      energy consumption (two orders of magnitude lower) reported so far for a plug
      type phase-change valve. Furthermore, its size, actuation mechanism and
      fabrication technology make it suitable for large-scale integration in
      microfluidic devices. Detailed characteristics in fabrication and actuation of
      the wax microfluidic valve as well as a test example of its performance for
      liquid dispensing are reported.

PMID- 27714008
TI  - Importance of proximity measures in clustering of cancer and miRNA datasets:
      proposal of an automated framework.
AB  - Distance plays an important role in the clustering process for allocating data
      points to different clusters. Several distance or proximity measures have been
      developed and reported in the literature to determine dissimilarities between two
      given points. The choice of distance measure depends on a particular domain as
      well as different data sets of the same domain. It is important to automatically
      determine the appropriate distance measure which acts best for a particular data
      set. In this study we have developed an automatic clustering technique using the
      search capability of multiobjective optimization which can automatically
      determine the relevant distance measure and the corresponding partitioning from a
      given data set. Our proposed automated framework is generic in nature i.e., any
      number of different distance measures can be incorporated into it. In our work we
      have used four existing widely used distance measures, i.e., Euclidean, line
      symmetry, point symmetry and city block distance to be explored for each data
      set. In order to measure the richness of an obtained partitioning using a
      particular distance, four cluster validity indices, the Silhouette index, the DB
      index, the adjusted rand index and classification accuracy are used. A new
      encoding strategy which can encode the set of cluster centers and the particular
      distance function is used to represent the problem. The appropriate distance
      function and the corresponding partitioning are determined using the search
      capability of a multiobjective optimization based technique. The efficiency of
      the proposed technique is shown on clustering three microRNA and three microarray
      gene expression data sets having varying complexities. The results show the
      usefulness of the proposed automated approach.

PMID- 27714009
TI  - Stiffness of the C-terminal disordered linker affects the geometry of the active
      site in endoglucanase Cel8A.
AB  - Cellulosomes are complex multi-enzyme machineries which efficiently degrade plant
      cell-wall polysaccharides. The multiple domains of the cellulosome proteins are
      often tethered together by intrinsically disordered regions. The properties and
      functions of these disordered linkers are not well understood. In this work, we
      study endoglucanase Cel8A, which is a relevant enzymatic component of the
      cellulosomes of Clostridium thermocellum. We use both all-atom and coarse-grained
      simulations to investigate how the conformations of the catalytic domain of Cel8A
      are affected by the disordered linker at its C terminus. We find that when the
      endoglucanase is bound to its substrate, the effective stiffness of the linker
      can influence the distances between groups of amino-acid residues throughout the
      entire enzymatic domain. In particular, variations in the linker stiffness can
      lead to small changes in the geometry of the active-site cleft. We suggest that
      such geometrical changes may have an effect on the catalytic activity of the
      enzyme.

PMID- 27714010
TI  - Correction: Nanoscale mechanics guides cellular decision making.
AB  - Correction for 'Nanoscale mechanics guides cellular decision making' by Zainab
      Rahil et al., Integr. Biol., 2016, DOI: .

PMID- 27714011
TI  - An on-demand gas segmented flow generator with high spatiotemporal resolution for
      in vivo analysis of neuronal response in C. elegans.
AB  - Studies of chemo-sensing in C. elegans to fluctuating gaseous cues are limited
      due to the lack of a method of precise gas control. In this paper, we describe a
      microfluidic-based on-demand gas segmented flow generator for performing
      fluctuating gaseous stimulations to worms. This highly versatile and programmable
      micro-device integrated with pneumatic valves for flexible and stable gas flow
      control and worm immobilization enabled us to examine the temporal features of
      neuronal response to multiple gas pulses with sub-second precision. As a result,
      we demonstrated the capability of the micro-device to generate repetitive gaseous
      chemical pulses with varying durations. By characterizing intracellular calcium
      signals, we showed that URX sensory neurons were sensitive to O2 pulses with
      duration of more than 0.5 s. Furthermore, URX neuronal adaptation and recovery in
      response to gaseous chemical pulses were investigated by varying the durations
      and intervals. The developed microfluidic system is shown to be a useful tool for
      studying the dynamics of in vivo gas-evoked neuronal responses and revealing the
      temporal properties of environmental stimulations.

PMID- 27714012
TI  - Molecular dynamics studies on the DNA-binding process of ERG.
AB  - The ETS family of transcription factors regulate gene targets by binding to a
      core GGAA DNA-sequence. The ETS factor ERG is required for homeostasis and
      lineage-specific functions in endothelial cells, some subset of haemopoietic
      cells and chondrocytes; its ectopic expression is linked to oncogenesis in
      multiple tissues. To date details of the DNA-binding process of ERG including DNA
      sequence recognition outside the core GGAA-sequence are largely unknown. We
      combined available structural and experimental data to perform molecular dynamics
      simulations to study the DNA-binding process of ERG. In particular we were able
      to reproduce the ERG DNA-complex with a DNA-binding simulation starting in an
      unbound configuration with a final root-mean-square-deviation (RMSD) of 2.1 A to
      the core ETS domain DNA-complex crystal structure. This allowed us to elucidate
      the relevance of amino acids involved in the formation of the ERG DNA-complex and
      to identify Arg385 as a novel key residue in the DNA-binding process. Moreover we
      were able to show that water-mediated hydrogen bonds are present between ERG and
      DNA in our simulations and that those interactions have the potential to achieve
      sequence recognition outside the GGAA core DNA-sequence. The methodology employed
      in this study shows the promising capabilities of modern molecular dynamics
      simulations in the field of protein DNA-interactions.

PMID- 27714013
TI  - Characterization of human pineal gland proteome.
AB  - The pineal gland is a neuroendocrine gland located at the center of the brain. It
      is known to regulate various physiological functions in the body through
      secretion of the neurohormone melatonin. Comprehensive characterization of the
      human pineal gland proteome has not been undertaken to date. We employed a high
      resolution mass spectrometry-based approach to characterize the proteome of the
      human pineal gland. A total of 5874 proteins were identified from the human
      pineal gland in this study. Of these, 5820 proteins were identified from the
      human pineal gland for the first time. Interestingly, 1136 proteins from the
      human pineal gland were found to contain a signal peptide domain, which indicates
      the secretory nature of these proteins. An unbiased global proteomic profile of
      this biomedically important organ should benefit molecular research to unravel
      the role of the pineal gland in neuropsychiatric and neurodegenerative diseases.

PMID- 27714014
TI  - Magnetophoretic transistors in a tri-axial magnetic field.
AB  - The ability to direct and sort individual biological and non-biological particles
      into spatially addressable locations is fundamentally important to the emerging
      field of single cell biology. Towards this goal, we demonstrate a new class of
      magnetophoretic transistors, which can switch single magnetically labeled cells
      and magnetic beads between different paths in a microfluidic chamber. Compared
      with prior work on magnetophoretic transistors driven by a two-dimensional in
      plane rotating field, the addition of a vertical magnetic field bias provides
      significant advantages in preventing the formation of particle clumps and in
      better replicating the operating principles of circuits in general. However, the
      three-dimensional driving field requires a complete redesign of the magnetic
      track geometry and switching electrodes. We have solved this problem by
      developing several types of transistor geometries which can switch particles
      between two different tracks by either presenting a local energy barrier or by
      repelling magnetic objects away from a given track, hereby denoted as "barrier"
      and "repulsion" transistors, respectively. For both types of transistors, we
      observe complete switching of magnetic objects with currents of ~40 mA, which is
      consistent over a range of particle sizes (8-15 MUm). The switching efficiency
      was also tested at various magnetic field strengths (50-90 Oe) and driving
      frequencies (0.1-0.6 Hz); however, we again found that the device performance
      only weakly depended on these parameters. These findings support the use of these
      novel transistor geometries to form circuit architectures in which cells can be
      placed in defined locations and retrieved on demand.

PMID- 27714015
TI  - A link between chromatin condensation mechanisms and Huntington's disease:
      connecting the dots.
AB  - Huntington's disease is a rare neurodegenerative disorder whose complex
      pathophysiology exhibits system-wide changes in the body, with striking and
      debilitating clinical features targeting the central nervous system. Among the
      various molecular functions affected in this disease, mitochondrial dysfunction
      and transcriptional dysregulation are some of the most studied aspects of this
      disease. However, there is evidence of the involvement of a mutant Huntingtin
      protein in the processes of DNA damage, chromosome condensation and DNA repair.
      This review attempts to briefly recapitulate the clinical features, model systems
      used to study the disease, major molecular processes affected, and, more
      importantly, examines recent evidence for the involvement of the mutant
      Huntingtin protein in the processes regulating chromosome condensation, leading
      to DNA damage response and neuronal death.

PMID- 27714016
TI  - Correction: Zinc is required to ensure the expression of flagella and the ability
      to form biofilms in Salmonella enterica sv Typhimurium.
AB  - Correction for 'Zinc is required to ensure the expression of flagella and the
      ability to form biofilms in Salmonella enterica sv Typhimurium' by Serena
      Ammendola et al., Metallomics, 2016, DOI: 10.1039/c6mt00108d.

PMID- 27714017
TI  - Electrocoalescence of paired droplets encapsulated in double-emulsion drops.
AB  - We utilize an ac electric field to trigger the on-demand fusion of two aqueous
      cores inside water-in-oil-in-water (W/O/W) double-emulsion drops. We attribute
      the coalescence phenomenon to field-induced structural polarization and breakdown
      of the stress balance at interfaces. This method provides not only accurate
      control over the reaction time of coalescence but also protection of the reaction
      from cross contamination.

PMID- 27714018
TI  - Enhanced energy harvesting by concentration gradient-driven ion transport in SBA
      15 mesoporous silica thin films.
AB  - Nanofluidic energy harvesting systems have attracted interest in the field of
      battery application, particularly for miniaturized electrical devices, because
      they possess excellent energy conversion capability for their size. In this
      study, a mesoporous silica (MPS)-based nanofluidic energy harvesting system was
      fabricated and selective ion transport in mesopores as a function of the salt
      gradient was investigated. Aqueous solutions with three different kinds of
      monovalent electrolytes-KCl, NaCl, and LiCl-with different diffusion coefficients
      (D+) were considered. The highest power density was 3.90 W m-2 for KCl, followed
      by 2.39 W m-2 for NaCl and 1.29 W m-2 for LiCl. Furthermore, the dependency of
      power density on the type of cation employed indicates that the harvested energy
      increases as the cation mobility increases, particularly at high concentrations.
      This cation-specific dependency suggests that the maximum power density increases
      by increasing the diffusion coefficient ratio of cations to anions, making this
      ratio a critical parameter in enhancing the performance of nanofluidic energy
      harvesting systems with extremely small pores ranging from 2 to 3 nm.

PMID- 27714019
TI  - Continuous plasma extraction under viscoelastic fluid in a straight channel with
      asymmetrical expansion-contraction cavity arrays.
AB  - In this paper, continuous plasma extraction under viscoelastic fluid in a
      straight channel with asymmetrical expansion-contraction cavity arrays (ECCA
      channel) is demonstrated by exploiting the Dean-flow-coupled elasto-inertial
      effects. First, the forces experienced by particles in the ECCA channel were
      discussed. Then, 4.8 MUm diameter particles, which mimic the behaviour of red
      blood cells (RBCs), were used to study the effects of poly(ethylene oxide) (PEO)
      concentrations and flow rates on particle viscoelastic focusing. Also, 3 MUm, 4.8
      MUm and 10 MUm diameter particles, which are comparable in size to platelets,
      RBCs, and white blood cells (WBCs), respectively, were used to study the effect
      of particle size on particle viscoelastic focusing. Finally, plasma extraction
      from diluted blood samples under viscoelastic conditions was conducted, and the
      purity of the collected blood plasma was measured. After two series of filtration
      with the same ECCA channel, the purity of 3 MUm, 4.8 MUm and 10 MUm diameter
      particles reached 100%, and the plasma purity reached 99.99%, as measured by a
      hemocytometer. In addition, flow cytometry data further validated the filtration
      performance of blood plasma. By exploiting the Dean-flow-coupled elasto-inertial
      effects, the ECCA channel offers a continuous, sheathless, and high purity plasma
      extraction.

PMID- 27714020
TI  - Flow-less and shape-conformable CNT sheet nanogenerator for self-powered motion
      sensor.
AB  - A carbon nanotube (CNT) sheet nanogenerator that does not require any liquid or
      gas flow for power generation is developed on the basis of Coulombic
      interactions, making the device attractive as a building block for self-powered
      sensors. The working principle of the CNT nanogenerator is probed in terms of
      sweeping speed, distance between charged object and nanotube sheet, surface
      charge, and number of layers of nanotube sheet. The nature of the CNT sheet and
      its formation process is such that simply winding the CNT sheet stripe n times
      around a substrate leads to increasing the power n times. For a practical
      demonstration of the CNT nanogenerator, a self-powered sensor array screen is
      developed that can read finger movements, just as with a finger command on a
      smartphone screen.

PMID- 27714021
TI  - Toxicological aspects of soluble titanium - a review of in vitro and in vivo
      studies.
AB  - Owing to the widespread use of titanium dioxide (TiO2) in various food, household
      and cosmetic products and in industry, the number of publications concerned with
      the potential toxic effects and health risks related to this substance in both
      bulk and nano form is steadily increasing. On the other hand, there is also a
      third form of titanium, ionic, which is produced by the biodegradation of Ti
      alloy implants. Thus, the growing population of implant recipients should raise
      concerns about the impact of soluble Ti on human health. Today, the mechanism of
      this metal's action on the human body is still not fully understood. This review
      aims to explore the health risks associated especially with long-term use of
      titanium implants. The paper provides an analysis of data available from the last
      10 years concerning investigations of the adverse effects of Ti ions, including
      in vitro models of various tissues, in vivo studies of implant corrosion in
      animals and humans, and potential pathomechanisms of the adverse health impact
      induced by soluble titanium.

PMID- 27714022
TI  - Hot off the press.
AB  - A personal selection of 32 recent papers is presented covering various aspects of
      current developments in bioorganic chemistry and novel natural products such as
      chrysamide A from a deep-sea fungus Penicillium chrysogenum.

PMID- 27714023
TI  - Launching deep subwavelength bulk plasmon polaritons through hyperbolic
      metamaterials for surface imaging with a tuneable ultra-short illumination depth.
AB  - Hyperbolic metamaterials (HMMs) composed of multiple nanometal-dielectric films
      are proposed for launching deep subwavelength bulk plasmon polaritons (BPPs) as
      uniform, large area surface imaging illumination sources with a skin depth even
      beyond 10 nm. Benefiting from the coupled plasmon modes over a wide wavevector
      range in HMMs, the illumination depth could be continually tuned, simply by
      adjusting the incidence angle of light impinged on a grating structure for BPP
      excitation. As an example, the illumination depths of 19-63 nm at a light
      wavelength of 532 nm are demonstrated with SiO2-Ag multifilms. Moreover, the
      structure holds its deep subwavelength illumination depth for a broad light
      wavelength range, resembling that of light total internal reflection in a prism
      with an ultra high refractive index. Furthermore, a fluorescent nanoparticle
      based micro-zone system was employed for estimating the illumination depth of the
      HMM structure. The method is believed to provide access for surface imaging
      features in ultra thin layers especially for bio-samples.

PMID- 27714024
TI  - Valence and oxide impurities in MoS2 and WS2 dramatically change their
      electrocatalytic activity towards proton reduction.
AB  - Layered molybdenum disulfide (MoS2) and tungsten disulfide (WS2) have received
      renewed interest in recent years as they are catalytic towards the hydrogen
      evolution reaction (HER) and they are touted as future replacements of platinum
      in electrolyzers. There is a significant discrepancy in the found onset
      potentials of MoS2 and WS2 towards the hydrogen evolution reaction. Here we show
      that the presence of valence sulfide impurities, such as MoS3 and WS3, and their
      oxide counterparts, such as MoO2, MoO3 and WO2, WO3 can contribute to the
      catalytic activity towards hydronium reduction to hydrogen of MoS2 and WS2.
      Therefore, it is highly possible that the differences in the reported onset
      potentials and thus catalytic activities of the MoS2 and WS2 are due to the
      presence of catalytic impurities.

PMID- 27714025
TI  - A label-free infrared opto-fluidic method for real-time determination of flow
      rate and concentration with temperature cross-sensitivity compensation.
AB  - The ability to accurately measure the flow rate, concentration, and temperature
      in real-time in micro total analysis systems (MUTAS) is crucial when improving
      their practical sensing capabilities within extremely small volumes. Our label
      free infrared (1500-1600 nm) opto-fluidic method, presented in this study,
      utilizes a cantilever-based flow meter integrated with two parallel optical fiber
      Fabry-Perot interferometers (FPIs). The first FPI serves as an ultra-sensitive
      flow meter and includes a Fiber Bragg Grating (FBG) tip for localized temperature
      sensing. The second FPI has a fabricated photopolymer micro-tip for highly
      sensitive refractive index (RI) determination. In this work, we performed 3-D
      simulation analysis to characterize cantilever deflection as well as temperature
      distribution and its effect on the RI. The experimental results from temperature
      cross-sensitivity analysis lead to real-time measurement resolutions of 5 nL min
      1, 1 * 10-6 RIU and 0.05  degrees C, for the flow rate, refractive index, and
      temperature, respectively.

PMID- 27714026
TI  - Multiplex SNP genotyping in whole blood using an integrated microfluidic lab-on-a
      chip.
AB  - Pharmacogenetics has often been touted as a cornerstone for precision medicine as
      detailed knowledge of a specific genetic makeup may allow for accurate
      predictions of a patient's individual drug response. Still, the widespread use of
      genetic tests is limited as they remain expensive and cumbersome, requiring
      sophisticated tools and highly trained personnel. In order for pharmacogenetics
      to reach its full potential, more cost-effective and easily accessible genotyping
      methods are desired. To meet these challenges, we present a silicon-based
      integrated microsystem for the detection of multiple single nucleotide
      polymorphisms (SNPs) directly from human blood. The device combines a blood lysis
      chamber, a cross-flow filter, a T-junction mixer, and a microreactor for
      quantitative polymerase chain reaction (qPCR). Using this device, successful on
      chip genotyping of two clinically relevant SNPs in human CYP2C9 gene was
      demonstrated with TaqMan assays, starting from blood. The two SNPs were detected
      simultaneously by introducing a sequence of plugs, each containing a different
      set of primers and probes. The method can be easily extended to detect several
      SNPs. The microsystem described here offers a rapid, reproducible, and accurate
      sample-to-answer technology enabling multiplex SNP profiling in point-of-care
      settings, bringing pharmacogenetics-based precision medicine a step closer to
      reality.

PMID- 27714027
TI  - Characterization of substrate binding and enzymatic removal of a 3-methyladenine
      lesion from genomic DNA with TAG of MDR A. baumannii.
AB  - The rise of multiple-drug resistance in bacterial pathogens imposes a serious
      public health concern and has led to increased interest in studying various
      pathways as well as enzymes. Different DNA glycosylases collaborate during
      bacterial infection and disease by overcoming the effects of ROS- and RNS
      mediated host innate immunity response. 3-Methyladenine DNA glycosylase I, an
      essential DNA repair enzyme, was chosen for the present study from the MDR
      species of A. baumannii. The enzyme was especially chosen because of its
      functional significance in A. baumannii and due to its structural variation from
      its human homologue. MDR strains such as A. baumannii are interesting targets
      owing to their evolved mechanisms of evading a host defence. In the absence of
      any structural information, the enzyme was characterized biophysically and
      biochemically. Binding studies with 3mA and Zn2+ indicated that the activity of
      TAG-Ab is an enthalpy-driven process. Fluorescence thermal denaturation studies
      described that the denaturation of TAG-Ab is a two-step process. Modified RP-HPLC
      based glycosylase assay attested that the heterologously expressed and purified
      TAG-Ab enzyme is active and catalyses the removal of 3mA. Other binding
      parameters and the effect of adenine on substrate binding are also discussed in
      detail.

PMID- 27714028
TI  - Robust scalable high throughput production of monodisperse drops.
AB  - Monodisperse drops with diameters between 20 MUm and 200 MUm can be used to
      produce particles or capsules for many applications such as for cosmetics, food,
      and biotechnology. Drops composed of low viscosity fluids can be conveniently
      made using microfluidic devices. However, the throughput of microfluidic devices
      is limited and scale-up, achieved by increasing the number of devices run in
      parallel, can compromise the narrow drop-size distribution. In this paper, we
      present a microfluidic device, the millipede device, which forms drops through a
      static instability such that the fluid volume that is pinched off is the same
      every time a drop forms. As a result, the drops are highly monodisperse because
      their size is solely determined by the device geometry. This makes the operation
      of the device very robust. Therefore, the device can be scaled to a large number
      of nozzles operating simultaneously on the same chip; we demonstrate the
      operation of more than 500 nozzles on a single chip that produces up to 150 mL h
      1 of highly monodisperse drops.

PMID- 27714029
TI  - Muscarine, imidazole, oxazole and thiazole alkaloids.
AB  - Covering: July 2012 to June 2015. Previous review: Nat. Prod. Rep., 2013, 30, 869
      915The structurally diverse imidazole-, oxazole-, and thiazole-containing
      secondary metabolites are widely distributed in terrestrial and marine
      environments, and exhibit extensive pharmacological activities. In this review
      the latest progress involving the isolation, biological activities, and chemical
      and biogenetic synthesis studies on these natural products has been summarized.

PMID- 27714030
TI  - Identification of potential CCR5 inhibitors through pharmacophore-based virtual
      screening, molecular dynamics simulation and binding free energy analysis.
AB  - CC chemokine receptor 5 (CCR5), a member of G protein-coupled receptors (GPCRs),
      plays a vital role in inflammatory responses to infection. Alterations in the
      expression of CCR5 have been correlated with disease progression in many types of
      cancers. The idea of using CCR5 as a target for therapeutic intervention has been
      demonstrated to prevent disease progression. To date, only a few compounds have
      been reported as CCR5 inhibitors. In this study, a series of CCR5 antagonists
      were used to construct pharmacophore models. Then the optimal model was utilized
      as a 3D query to identify novel chemical entities from structural databases.
      After refinement by molecular docking, drug-likeness analysis, molecular dynamics
      simulations (MDS) and binding free energy analysis, three potential inhibitors
      (25, 29 and 45) were identified. MD simulations suggested that the screened
      compounds retained the important common binding mode known for CCR5 inhibitors
      (maraviroc and nifeviroc), which occupied the bottom of a pocket and stabilized
      the conformation of CCR5. During the binding process, van der Waals interactions
      provided the substantial driving force. The most favorable contributions were
      from Tyr37, Trp86, Tyr89, Tyr108, Phe109, Phe112, Gln194, Thr195, Ile198, Trp248,
      Tyr251, Leu255, Thr259, Met279, Glu283 and Met287. The above results suggest that
      the hybrid strategy would provide a basis for rational drug design.

PMID- 27714031
TI  - Designing metallodrugs with nuclease and protease activity.
AB  - The accidental discovery of cisplatin some 50 years ago generated renewed
      interest in metallopharmaceuticals. Beyond cisplatin, many useful metallodrugs
      have been synthesized for the diagnosis and treatment of various diseases, but
      toxicity concerns, and the propensity to induce chemoresistance and secondary
      cancers make it imperative to search for novel metallodrugs that address these
      limitations. The Amino Terminal Cu(ii) and Ni(ii) (ATCUN) binding motif has
      emerged as a suitable template to design catalytic metallodrugs with nuclease and
      protease activities. Unlike their classical counterparts, ATCUN-based
      metallodrugs exhibit low toxicity, employ novel mechanisms to irreversibly
      inactivate disease-associated genes or proteins providing in principle, a channel
      to circumvent the rapid emergence of chemoresistance. The ATCUN motif thus
      presents novel strategies for the treatment of many diseases including cancers,
      HIV and infections caused by drug-resistant bacteria at the genetic level. This
      review discusses their design, mechanisms of action and potential for further
      development to expand their scope of application.

PMID- 27714032
TI  - Insight into a reversible energy transfer system.
AB  - Resonance energy transfer (RET) processes have wide applications; these processes
      involve a unidirectional energy transfer from a particular donor to a particular
      acceptor. Here, we report a plasmonic resonance energy transfer (PRET), which
      occurs from the surface of gold nanoparticles to fluorescent organic dyes, and
      coexists with a nanometal surface energy transfer (NSET) that operates in the
      reverse direction. The coexistence of both PRET and NSET in opposite directions
      means that the roles of both donor and acceptor can be interchanged, which could
      be identified by using spectrofluorometric measurements and light scattering dark
      field microscopic imaging. The experimental data could be further theoretically
      supported using Persson and Lang's model, the quasi-static approximation and
      finite-difference time-domain simulation. Moreover, disruption of the PRET
      process by altering the energy transfer pairs suggests that interactions occur
      inside the reversible energy transfer system, which manifest by increasing the
      fluorescence quenching efficiency of the NSET process.

PMID- 27714033
TI  - Integration of DNA and graphene oxide for the construction of various advanced
      logic circuits.
AB  - Multiple advanced logic circuits including the full-adder, full-subtract and
      majority logic gate have been successfully realized on a DNA/GO platform for the
      first time. All the logic gates were implemented in an enzyme-free condition. The
      investigation provides a wider field of vision towards prototypical DNA-based
      algebra logical operations and promotes the development of advanced logic
      circuits.

PMID- 27714034
TI  - Protein-coding genes combined with long non-coding RNAs predict prognosis in
      esophageal squamous cell carcinoma patients as a novel clinical multi-dimensional
      signature.
AB  - Esophageal carcinoma is one of the most malignant gastrointestinal cancers
      worldwide, and has a high mortality rate. Both protein-coding genes (PCGs) and
      long non-coding RNAs (lncRNAs) have been shown to play an important role in the
      development of malignant tumors. However, the clinical significance of PCGs
      combined lncRNAs is yet to be investigated in esophageal squamous cell carcinoma
      (ESCC). Using probe re-annotation, univariable Cox regression and the random
      survival forest algorithm to identify PCG-lncRNA combinations predictive of the
      overall survival, we found a signature comprised of three PCGs (ANGPTL7, OBP2A,
      SLC27A5) and two lncRNAs (RP11-702B10.1, RP11-523H24.3) to have the highest
      accurate prediction, with an area under ROC curve (AUC) of 0.85 in the training
      group and 0.63 in the test group, and it was significantly associated with the
      survival of ESCC patients in the training group (median survival: 32.2 months >
      60 months, P < 0.001). The application of the signature to the test group showed
      similar prognostic values (median survival: 39.3 months vs. >60 months, P =
      0.03). The chi-square test and multivariable Cox regression analysis showed that
      the three-PCG, two-lncRNA signature was an independent prognostic factor for
      patients with ESCC. Stratified analysis suggested that the PCG-lncRNA signature
      combined with the TNM stage could more accurately categorize ESCC patients. Our
      study suggests that the three-PCG, two-lncRNA signature has clinical significance
      for the prognosis of patients with ESCC. This signature can serve as a potential
      auxiliary biomarker of the TNM stage to subdivide ESCC patients more precisely.

PMID- 27714035
TI  - Nonlinear Rashba spin splitting in transition metal dichalcogenide monolayers.
AB  - Single-layer transition-metal dichalcogenides (TMDs) such as MoS2 and MoSe2
      exhibit unique electronic band structures ideal for hosting many exotic spin
      orbital orderings. It has been widely accepted that Rashba spin splitting (RSS)
      is linearly proportional to the external field in heterostructure interfaces or
      to the potential gradient in polar materials. Surprisingly, an extraordinary
      nonlinear dependence of RSS is found in semiconducting TMD monolayers under a
      gate field. In contrast to small and constant RSS in polar materials, the
      potential gradient in non-polar TMDs gradually increases with the gate bias,
      resulting in nonlinear RSS with a Rashba coefficient an order-of-magnitude larger
      than the linear one. Most strikingly, under a large gate field MoSe2 demonstrates
      the largest anisotropic spin splitting among all known semiconductors to our
      knowledge. Based on the k.p model via symmetry analysis, we identify that the
      third-order contributions are responsible for the large nonlinear Rashba
      splitting. The gate tunable spin splitting found in semiconducting pristine TMD
      monolayers promises future spintronics applications in that spin polarized
      electrons can be generated by external gating in an experimentally accessible
      way.

PMID- 27714036
TI  - A solid-state cation exchange reaction to form multiple metal oxide
      heterostructure nanowires.
AB  - Metal oxide nanostructures have been investigated extensively due to their wide
      range of physical properties; zinc oxide is one of the most promising materials.
      It exhibits fascinating functional properties and various types of morphologies.
      In particular, ZnO heterostructures have attracted great attention because their
      performance can be modified and further improved by the addition of other
      materials. In this study, we successfully transformed ZnO nanowires (NWs) into
      multiple ZnO/Al2O3 heterostructure NWs via a solid-state cation exchange
      reaction. The experiment was carried out in situ via an ultrahigh vacuum
      transmission electron microscope (UHV-TEM), which was equipped with a video
      recorder. Moreover, we analyzed the structure and composition of the
      heterostructure NWs by Cs-corrected STEM equipped with EDS. Based on these
      experimental results, we inferred a cation exchange reaction ion path model.
      Additionally, we investigated the defects that appeared after the cation
      reaction, which resulted from the remaining zinc ions. These multiple
      heterostructure ZnO/Al2O3 NWs exhibited excellent UV sensing sensitivity and
      efficiency.

PMID- 27714037
TI  - Ultra-efficient electrocatalytic hydrogen evolution at one-step carbonization
      generated molybdenum carbide nanosheets/N-doped carbon.
AB  - The hydrogen evolution reaction (HER) from water through electrocatalysis using
      highly active noble metal-free catalysts as an alternative to precious Pt-based
      catalysts holds great promise for clean and renewable energy systems. Here, Mo2C
      nanosheets well-regulated in N-doped carbon (MCNS/NC)are facilely achieved by in
      situ confining carburization of a Mo-based inorganic-organic lamellar
      mesostructure at 900  degrees C, and demonstrated for the first time as an ultra
      efficient and durable HER catalyst. The MCNS/NC displays a very low onset
      overpotential of ~0 mV and an overpotential of 19 mV at 10 mA cm-2 with a small
      Tafel slope of 28.9 mV dec-1 in acid media, which is remarkably superior to most
      other transition metal-based catalysts and comparable to commercial Pt/C. The HER
      kinetics are further studied by EIS and Tafel slope analysis, suggesting the
      dominant Volmer-Tafel mechanism. An "outside-in" carburization mechanism for the
      evolution of MCNS/NC is proposed through detailed investigation of the samples
      annealed at different temperatures. This study highlights the importance of
      designing well-regulated functional nanostructures combined with a conductive
      carbonaceous matrix for versatile applications.

PMID- 27714038
TI  - Coated and uncoated cellophane as materials for microplates and open-channel
      microfluidics devices.
AB  - This communication describes the use of uncoated cellophane (regenerated
      cellulose films) for the fabrication of microplates, and the use of coated
      cellophane for the fabrication of open-channel microfluidic devices. The
      microplates based on uncoated cellophane are particularly interesting for
      applications that require high transparency in the ultraviolet (UV) regime, and
      offer a low-cost alternative to expensive quartz-well plates. Uncoated cellophane
      is also resistant to damage by various solvents. The microfluidic devices, based
      on coated cellophane, can have features with dimensions as small as 500 MUm, and
      complex, non-planar geometries. Electrodes can be printed on the surface of the
      coated cellophane, and embedded in microfluidic devices, to develop resistive
      heaters and electroanalytical devices for flow injection analysis, and continuous
      flow electrochemiluminescence (ECL) applications. These open-channel devices are
      appropriate for applications where optical transparency (especially in the
      visible regime), resistance to damage by water, biocompatibility and
      biodegradability are important. Cellophane microfluidic systems complement
      existing cellulose-based paper microfluidic systems, and provide an alternative
      to other materials used in microfluidics, such as synthetic polymers or glass.
      Cellulose films are plausible materials for uses in integrated microfluidic
      systems for diagnostics, analyses, cell-culture, and MEMS.

PMID- 27714039
TI  - Unveiling the atomic structure and electronic properties of atomically thin boron
      sheets on an Ag(111) surface.
AB  - Two-dimensional (2D) boron sheets (i.e., borophene) have a huge potential as a
      basic building block in nanoelectronics and optoelectronics; such a situation is
      greatly promoted by recent experiments on fabrication of borophene on silver
      substrates. However, the fundamental atomic structure of borophene on the Ag
      substrate is still under debate, which greatly impedes further exploration of its
      properties. Herein, the atomic structure and electronic properties of borophene
      on an Ag(111) surface have been studied using first-principles calculations and
      ab initio molecular dynamics simulations. Our results reveal that there exist
      three energetically favorable borophene structures (beta5, chi1, and chi2) on the
      Ag(111) surface and their simulated STM images are in good agreement with
      experimental results, suggesting the coexistence of boron phases during the
      growth. All these stable borophene structures have a planar structure with slight
      surface buckling (~0.15 A) and relatively high hexagonal vacancy density (1/6 and
      1/5) and exhibit typical metallic conductivity. These findings not only can be
      applied to solve the experimental controversies about the atomic structure of
      borophene on the Ag substrate but also provide a theoretical basis for exploring
      the fundamental properties and applications of 2D boron sheets.

PMID- 27714040
TI  - Photon-induced generation and spatial control of extreme pressure at the
      nanoscale with a gold bowtie nano-antenna platform.
AB  - Precise spatial and temporal control of pressure stimulation at the nanometer
      scale is essential for the fabrication and manipulation of nano-objects, and for
      exploring single-molecule behaviour of matter under extreme conditions. However,
      state-of-the-art nano-mechanical transducers require sophisticated driving
      hardware and are currently limited to moderate pressure regimes. Here we report a
      gold plasmonic bowtie (AuBT) nano-antennas array that can generate extreme
      pressure stimulus of ~100 GPa in the ps (10-12 s) time scale with sub-wavelength
      resolution upon irradiation with ultra-short laser pulses. Our method leverages
      the non-linear interaction of photons with water molecules to excite a nano
      plasma in the plasmon-enhanced near-field and induce extreme thermodynamic
      states. The proposed method utilizes laser pulses, which in contrast to micro-
      and nano-mechanical actuators offers simplicity and versatility. We present time
      resolved shadowgraphic imaging, electron microscopy and simulation data that
      suggest that our platform can efficiently create cavitation nano-bubbles and
      generate intense pressure in specific patterns, which can be controlled by the
      selective excitation of plasmon modes of distinct polarizations. This novel
      platform should enable probing non-invasively the mechanical response of cells
      and single-molecules at time and pressure regimes that are currently difficult to
      reach with other methods.

PMID- 27714041
TI  - The 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one alkaloids. Results of 20
      years of research, uncovering a new family of natural products.
AB  - Covering: up to April 2016Aspergillus and Penicillium are fungal species known to
      produce a high diversity of secondary metabolites, many of them endowed with
      interesting bioactivity. The small but steadily growing family of the naturally
      occurring 5-hydroxy-4-aryl-quinolin-2(1H)-one alkaloids and closely related
      compounds, which represent the results of various research projects that spanned
      over 20 years and involved scientists from different continents, are covered
      here. Emphasis is placed on the isolation and chemical structures of the
      different compounds, together with their source microorganisms, environmental
      conditions, country or region of origin, and relevant biological activities. In
      addition, stereochemical aspects, as well as the proposed biosynthetic pathways
      for the different members, and the incipient synthetic efforts towards some of
      the compounds or their key intermediates, are discussed in detail.

PMID- 27714042
TI  - BiKEGG: a COBRA toolbox extension for bridging the BiGG and KEGG databases.
AB  - Development of an interface tool between the Biochemical, Genetic and Genomic
      (BiGG) and KEGG databases is necessary for simultaneous access to the features of
      both databases. For this purpose, we present the BiKEGG toolbox, an open source
      COBRA toolbox extension providing a set of functions to infer the reaction
      correspondences between the KEGG reaction identifiers and those in the BiGG
      knowledgebase using a combination of manual verification and computational
      methods. Inferred reaction correspondences using this approach are supported by
      evidence from the literature, which provides a higher number of reconciled
      reactions between these two databases compared to the MetaNetX and MetRxn
      databases. This set of equivalent reactions is then used to automatically
      superimpose the predicted fluxes using COBRA methods on classical KEGG pathway
      maps or to create a customized metabolic map based on the KEGG global metabolic
      pathway, and to find the corresponding reactions in BiGG based on the genome
      annotation of an organism in the KEGG database. Customized metabolic maps can be
      created for a set of pathways of interest, for the whole KEGG global map or
      exclusively for all pathways for which there exists at least one flux carrying
      reaction. This flexibility in visualization enables BiKEGG to indicate reaction
      directionality as well as to visualize the reaction fluxes for different static
      or dynamic conditions in an animated manner. BiKEGG allows the user to export (1)
      the output visualized metabolic maps to various standard image formats or save
      them as a video or animated GIF file, and (2) the equivalent reactions for an
      organism as an Excel spreadsheet.

PMID- 27714043
TI  - Investigation of uranium interactions with calcium phosphate-binding proteins
      using ICP/MS and CE-ICP/MS.
AB  - During long-term exposure, uranium accumulates in bone. Since uranium in U(vi)
      complexes shares similar coordination properties to calcium, this toxicant is
      assumed to be exchanged with calcium ions at the surfaces of bone mineral
      crystals. Recently, two proteins involved in bone turnover, fetuin A and
      osteopontin, were shown to exhibit a high affinity for U(vi). A common
      biochemical feature of both fetuin A and osteopontin is their inhibiting role in
      calcium phosphate precipitation. Therefore it is conceivable that complexation of
      U(vi) with these proteins may alter their interaction with calcium and/or calcium
      phosphate. Quantitative analyses of calcium, phosphorus and uranium performed
      using inductively coupled plasma/mass spectrometry (ICP/MS) demonstrated the
      inhibition of the precipitation of calcium phosphate by fetuin A and osteopontin
      for 2 h. In addition, the presence of U(vi) did not seem to alter the duration of
      this process. However, dynamic light scattering studies revealed that the size of
      the colloidal particles formed with osteopontin was altered by the presence of
      U(vi) in a concentration-dependent manner. Finally, using hyphenated capillary
      electrophoresis-ICP/MS (CE-ICP/MS), we showed that in these systems, at a low
      concentration of U(vi) (protein : U(vi) 8 : 1), U(vi) might remain in solution by
      forming a complex with proteins and not by sequestration of a precipitate of
      either autunite or uranyl orthophosphate.

PMID- 27714044
TI  - Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully
      differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells.
AB  - Intestinal iron absorption is highly regulated since no mechanism for iron
      excretion exists. We previously demonstrated that expression of an intestinal
      copper transporter (Atp7a) increases in parallel with genes encoding iron
      transporters in the rat duodenal epithelium during iron deprivation (Am. J.
      Physiol.: Gastrointest. Liver Physiol., 2005, 288, G964-G971). This led us to
      postulate that Atp7a may influence intestinal iron flux. Therefore, to test the
      hypothesis that Atp7a is required for optimal iron transport, we silenced Atp7a
      in rat IEC-6 and human Caco-2 cells. Iron transport was subsequently quantified
      in fully-differentiated cells plated on collagen-coated, transwell inserts.
      Interestingly, 59Fe uptake and efflux were impaired in both cell lines by Atp7a
      silencing. Concurrent changes in the expression of key iron transport-related
      genes were also noted in IEC-6 cells. Expression of Dmt1 (the iron importer),
      Dcytb (an apical membrane ferrireductase) and Fpn1 (the iron exporter) was
      decreased in Atp7a knockdown (KD) cells. Paradoxically, cell-surface
      ferrireductase activity increased (>5-fold) in Atp7a KD cells despite decreased
      Dcytb mRNA expression. Moreover, increased expression (>10-fold) of hephaestin
      (an iron oxidase involved in iron efflux) was associated with increased
      ferroxidase activity in KD cells. Increases in ferrireductase and ferroxidase
      activity may be compensatory responses to increase iron flux. In summary, in
      these reductionist models of the mammalian intestinal epithelium, Atp7a KD
      altered expression of iron transporters and impaired iron flux. Since Atp7a is a
      copper transporter, it is a logical supposition that perturbations in
      intracellular copper homeostasis underlie the noted biologic changes in these
      cell lines.

PMID- 27714046
TI  - Gap controlled plasmon-dielectric coupling effects investigated with single
      nanoparticle-terminated atomic force microscope probes.
AB  - Precise positioning of a plasmonic nanoparticle (NP) near a small dielectric
      surface is not only necessary for understanding gap-dependent interactions
      between a metal and dielectric but it is also a critical component in building
      ultrasensitive molecular rulers and force sensing devices. In this study we
      investigate the gap-dependent scattering of gold and silver NPs by controllably
      depositing them on an atomic force microscope (AFM) tip and monitoring their
      scattering within the evanescent field of a tin dioxide nanofiber waveguide. The
      enhanced distance-dependent scattering profiles due to plasmon-dielectric
      coupling effects show similar decays for both gold and silver NPs given the
      strong dependence of the coupling on the decaying power in the near-field.
      Experiments and simulations also demonstrate that the NPs attached to the AFM
      tips act as free NPs, eliminating optical interference typically observed from
      secondary dielectric substrates. With the ability to reproducibly place
      individual plasmonic NPs on an AFM tip, and optically monitor near-field plasmon
      dielectric coupling effects, this approach allows a wide-variety of light-matter
      interactions studies to be carried out on other low-dimensional nanomaterials.

PMID- 27714047
TI  - The role of carbon precursor on carbon nanotube chirality in floating catalyst
      chemical vapour deposition.
AB  - We have studied the influence of different carbon precursors (methane, ethanol
      and toluene) on the type, diameter and chiral angle distributions of carbon
      nanotubes (CNTs) grown with the floating catalyst technique in a horizontal gas
      flow reactor. Using electron diffraction to study their atomic structures, we
      found that ethanol and toluene precursors gave high single-wall CNT yields (92%
      and 89% respectively), with narrow diameter distributions: 1.1 nm to 1.7 nm
      (ethanol); 1.3 nm to 2.1 nm (toluene), with a propensity for armchair-type chiral
      angles. In contrast, methane-grown CNTs gave high double-wall CNT yields (75%)
      with broader diameter populations: 1.2 to 4.6 nm (inner CNT) and 2.2 to 5.3 nm
      (outer CNT) with a more uniform spread of chiral angles, but weakly peaked around
      15 to 20 degrees. These observations agree with known growth models. However,
      double-wall CNTs grown with toluene showed an unusually narrow interlayer spacing
      of 0.286 +/- 0.003 nm with suggestions of large, 20 degrees  to 25 degrees ,
      differences between inner and outer CNT chiral angles. Methane gave a large
      interlayer spacing (0.385 +/- 0.002 nm) with suggestions of small 5 degrees  to
      10 degrees  inter-tube chirality correlations.

PMID- 27714045
TI  - Mammalian Fe-S proteins: definition of a consensus motif recognized by the co
      chaperone HSC20.
AB  - Iron-sulfur (Fe-S) clusters are inorganic cofactors that are fundamental to
      several biological processes in all three kingdoms of life. In most organisms, Fe
      S clusters are initially assembled on a scaffold protein, ISCU, and subsequently
      transferred to target proteins or to intermediate carriers by a dedicated
      chaperone/co-chaperone system. The delivery of assembled Fe-S clusters to
      recipient proteins is a crucial step in the biogenesis of Fe-S proteins, and, in
      mammals, it relies on the activity of a multiprotein transfer complex that
      contains the chaperone HSPA9, the co-chaperone HSC20 and the scaffold ISCU. How
      the transfer complex efficiently engages recipient Fe-S target proteins involves
      specific protein interactions that are not fully understood. This mini review
      focuses on recent insights into the molecular mechanism of amino acid motif
      recognition and discrimination by the co-chaperone HSC20, which guides Fe-S
      cluster delivery.

PMID- 27714048
TI  - Skin-mountable stretch sensor for wearable health monitoring.
AB  - This work presents a wrinkled Platinum (wPt) strain sensor with tunable strain
      sensitivity for applications in wearable health monitoring. These stretchable
      sensors show a dynamic range of up to 185% strain and gauge factor (GF) of 42.
      This is believed to be the highest reported GF of any metal thin film strain
      sensor over a physiologically relevant dynamic range to date. Importantly,
      sensitivity and dynamic range are tunable to the application by adjusting wPt
      film thickness. Performance is reliable over 1000 cycles with low hysteresis
      after sensor conditioning. The possibility of using such a sensor for real-time
      respiratory monitoring by measuring chest wall displacement and correlating with
      lung volume is demonstrated.

PMID- 27714049
TI  - Flexible hierarchical membranes of WS2 nanosheets grown on graphene-wrapped
      electrospun carbon nanofibers as advanced anodes for highly reversible lithium
      storage.
AB  - It is still very challenging to achieve effective combination of carbon
      nanofibers and graphene sheets. In this study, a novel and facile method is
      developed to prepare flexible graphene/carbon nanofiber (GCNF) membranes with
      every carbon nanofiber wrapped by conductive graphene sheets, resulting in a
      remarkable improvement of their electrical conductivity. This method only entails
      a moderate process of soaking the pre-oxidized electrospun polyacrylonitrile
      (oPAN) nanofiber membranes in graphene oxide (GO) aqueous dispersion, and
      subsequent carbonization of the GO/oPAN hybrid membranes. By using the highly
      conductive GCNF membrane as a template, hierarchical WS2/GCNF hybrid membranes
      with few-layer WS2 nanosheets uniformly grown on GCNF nanofibers were fabricated
      as high-performance anodes for lithium ion batteries. Benefiting from the
      synergistic effects of GCNF nanofibers and WS2 nanosheets, the resulting WS2/GCNF
      hybrid membranes possessed a porous structure, large specific surface area, high
      electrical conductivity and good structural integrity, which are favorable for
      the rapid diffusion of lithium ions, fast transfer of electrons and overall
      electrochemical stability. As a result, the optimized WS2/GCNF hybrid membrane
      exhibited a high initial charge capacity of 1128.2 mA h g-1 at a current density
      of 0.1 A g-1 and outstanding cycling stability with 95% capacity retention after
      100 cycles.

PMID- 27714050
TI  - Nonassociative learning implementation by a single memristor-based multi-terminal
      synaptic device.
AB  - Animals' survival is dependent on their abilities to adapt to the changing
      environment by adjusting their behaviours, which is related to the ubiquitous
      learning behaviour, nonassociative learning. Thus mimicking the indispensable
      learning behaviour in organisms based on electronic devices is vital to better
      achieve artificial neural networks and neuromorphic computing. Here a three
      terminal device consisting of an oxide-based memristor and a NMOS transistor is
      proposed. The memristor with gradual conductance tuning inherently functions as
      the synapse between sensor neurons and motor neurons and presents adjustable
      synaptic plasticity, while the NMOS transistor attached to the memristor is
      utilized to mimic the modulatory effect of the neuromodulator released by inter
      neurons. Such a memristor-based multi-terminal device allows the practical
      implementation of significant nonassociative learning based on a single
      electronic device. In this study, the experience-induced modification behaviour,
      both habituation and sensitization, was successfully achieved. The dependence of
      the nonassociative behavioural response on the strength and interval of presented
      stimuli was also discussed. The implementation of nonassociative learning offers
      feasible and experimental advantages for further study on neuromorphic systems
      based on electronic devices.

PMID- 27714051
TI  - Rational design of Pt-Ni-Co ternary alloy nanoframe crystals as highly efficient
      catalysts toward the alkaline hydrogen evolution reaction.
AB  - The rational design of highly efficient electrocatalysts for the hydrogen
      evolution reaction (HER) is of prime importance for establishing renewable and
      sustainable energy systems. The alkaline HER is particularly challenging as it
      involves a two-step reaction of water dissociation and hydrogen recombination,
      for which platinum-based binary catalysts have shown promising activity. In this
      work, we synthesized high performance platinum-nickel-cobalt alloy nanocatalysts
      for the alkaline HER through a simple synthetic route. This ternary nanostructure
      with a Cartesian-coordinate-like hexapod shape could be prepared by a one-step
      formation of core-dual shell Pt@Ni@Co nanostructures followed by a selective
      removal of the Ni@Co shell. The cobalt precursor brings about a significant
      impact on the control of size and shape of the nanostructure. The PtNiCo
      nanohexapods showed a superior alkaline HER activity to Pt/C and binary PtNi
      hexapods, with 10 times greater specific activity than Pt/C. In addition, the
      PtNiCo nanohexapods demonstrated excellent activity and durability for the oxygen
      reduction reaction in acidic media.

PMID- 27714052
TI  - Growth of MoSe2 nanosheets with small size and expanded spaces of (002) plane on
      the surfaces of porous N-doped carbon nanotubes for hydrogen production.
AB  - MoSe2 nanosheets with small size and expanded spaces between the (002) planes
      were grown on the surfaces of porous N-doped carbon nanotubes (NCNTs) with much
      higher HER activity than carbon nanotubes without N dopants. Owing to the
      synergistic effects between the MoSe2 nanosheets and the porous NCNT substrate,
      MoSe2/NCNTs exhibit superior HER activity to layered metal chalcogenides reported
      previously.

PMID- 27714053
TI  - Decoupling the shape parameter to assess gold nanorod uptake by mammalian cells.
AB  - The impact of nanoparticles (NPs) upon biological systems can be fundamentally
      associated with their physicochemical parameters. A further often-stated tenet is
      the importance of NP shape on rates of endocytosis. However, given the convoluted
      parameters concerning the NP-cell interaction, it is experimentally challenging
      to attribute any findings to shape alone. Herein we demonstrate that shape, below
      a certain limit, which is specific to nanomedicine, is not important for the
      endocytosis of spherocylinders by either epithelial or macrophage cells in vitro.
      Through a systematic approach, we reshaped a single batch of gold nanorods into
      different aspect ratios resulting in near-spheres and studied their cytotoxicity,
      (pro-)inflammatory status, and endocytosis/exocytosis. It was found that on a
      length scale of ~10-90 nm and at aspect ratios less than 5, NP shape has little
      impact upon their entry into either macrophages or epithelial cells. Conversely,
      nanorods with an aspect ratio above 5 were preferentially endocytosed by
      epithelial cells, whereas there was a lack of shape dependent uptake following
      exposure to macrophages in vitro. These findings have implications both in the
      understanding of nanoparticle reshaping mechanisms, as well as in the future
      rational design of nanomaterials for biomedical applications.

PMID- 27714054
TI  - A flexible field-limited ordered ZnO nanorod-based self-powered tactile sensor
      array for electronic skin.
AB  - A tactile sensor is an essential component for realizing biomimetic robots, while
      the flexibility of the tactile sensor is a pivotal feature for its application,
      especially for electronic skin. In this work, a flexible self-powered tactile
      sensor array was designed based on the piezoelectricity of ZnO nanorods (NRs).
      The field-limited ordered ZnO NRs were synthesized on a flexible Kapton substrate
      to serve as the functional layer of the tactile sensor. The electrical output
      performances of the as-fabricated tactile sensor were measured under pressing and
      bending forces. Moreover, we measured the human-finger pressure detection
      performance of the tactile sensor array, suggesting that the corresponding
      mapping figure of finger pressure could be displayed on the monitor of a personal
      computer (PC) in the form of lighted LED and color density through a LabVIEW
      system. This as-grown sensory feedback system should be of potential valuable
      assistance for the users of hand prostheses to reduce the risk and obtain a
      greater feeling of using the prostheses.

PMID- 27714055
TI  - Strong dichroic emission in the pseudo one dimensional material ZrS3.
AB  - Zirconium trisulphide (ZrS3), a member of the layered transition metal
      trichalcogenides (TMTCs) family, has been studied by angle-resolved
      photoluminescence spectroscopy (ARPLS). The synthesized ZrS3 layers possess a
      pseudo one-dimensional nature where each layer consists of ZrS3 chains extending
      along the b-lattice direction. Our results show that the optical properties of
      few-layered ZrS3 are highly anisotropic as evidenced by large PL intensity
      variation with the polarization direction. Light is efficiently absorbed when the
      E-field is polarized along the chain (b-axis), but the field is greatly
      attenuated and absorption is reduced when it is polarized vertical to the 1D-like
      chains as the wavelength of the exciting light is much longer than the width of
      each 1D chain. The observed PL variation with polarization is similar to that of
      conventional 1D materials, i.e., nanowires, and nanotubes, except for the fact
      that here the 1D chains interact with each other giving rise to a unique linear
      dichroism response that falls between the 2D (planar) and 1D (chain) limit. These
      results not only mark the very first demonstration of PL polarization anisotropy
      in 2D systems, but also provide novel insight into how the interaction between
      adjacent 1D-like chains and the 2D nature of each layer influences the overall
      optical anisotropy of pseudo-1D materials. Results are anticipated to have an
      impact on optical technologies such as polarized detectors, near-field imaging,
      communication systems, and bio-applications relying on the generation and
      detection of polarized light.

PMID- 27714056
TI  - White-light-emitting magnetite nanoparticle-polymer composites: photonic
      reactions of magnetic multi-granule nanoclusters as photothermal agents.
AB  - Magnetite nanoparticles combined with polymers produce white-light emission under
      multiphoton laser irradiation. Understanding the photonic reaction in magnetite
      polymer composites is critical for application of magnetite NPs as photothermal
      agents. Laser irradiated magnetite nanoparticle-poly(methyl methacrylate) (PMMA)
      composites exhibit fluorescence due to the carbon double-bond formation resulting
      from the oxidation of the PMMA.

PMID- 27714057
TI  - Rhodamine-doped nanoporous polymer films as high-performance anti-reflection
      coatings and optical filters.
AB  - We demonstrate a simple and robust procedure for the fabrication of rhodamine
      doped nanoporous poly(methyl methacrylate) (PMMA) films, whose optical
      properties, such as anti-reflection, fluorescence and absorption can be tailored
      to specific applications. By exploiting phase separation of a binary polymer
      blend (PMMA and polystyrene), we fabricated foam-like nanoporous films that could
      be easily and cost-effectively integrated into the fabrication process of optical
      components. We link film morphology, studied by multifrequency atomic force
      microscopy (AFM), to the effective refractive index of the films for use as anti
      reflection coatings. The film's morphology leads to superior broadband anti
      reflection performance compared with homogeneous films. For applications
      involving optical filters and spectral conversion layers (e.g., for photovoltaic
      applications), we doped the films with the fluorescent molecule rhodamine,
      whereby simple variations in the fabrication process enabled us to prepare
      rhodamine-doped nanoporous PMMA with tunable fluorescence and absorption, without
      losing the anti-reflective properties. The above combination of optical
      properties makes the films attractive for a wide range of applications.

PMID- 27714058
TI  - Self-adjusted all-dielectric metasurfaces for deep ultraviolet femtosecond pulse
      generation.
AB  - The advantage of metasurfaces and nanostructures with a high nonlinear response
      is that they do not require phase matching, and the generated pulses are short in
      the time domain without additional pulse compression. However, the fabrication of
      large-scale planar structures by lithography-based methods is expensive, time
      consuming, and requires complicated preliminary simulations to obtain the most
      optimized geometry. Here, we propose a novel strategy for the self-assembled
      fabrication of large-scale resonant metasurfaces, where incident femtosecond
      laser pulses adjust the initial silicon films via specific surface deformation to
      be as resonant as possible for a given wavelength. The self-adjusting approach
      eliminates the necessity of multistep lithography and designing, because
      interference between the incident and the scattered parts of each laser pulse
      "imprints" resonant field distribution within the film. The self-adjusted
      metasurfaces demonstrate a high damage threshold (~1012 W cm-2) and efficient
      frequency conversion from near-IR to deep UV. The conversion efficiency is up to
      30-fold higher compared with nonresonant smooth Si films. The resulting
      metasurfaces allow for the generation of UV femtosecond laser pulses at a
      wavelength of 270 nm with a high peak and average power (~105 W and ~1.5 MUW,
      respectively). The results pave the way to the creation of ultrathin nonlinear
      metadevices working at high laser intensities for efficient deep UV generation at
      the nanoscale.

PMID- 27714059
TI  - In situ fabrication of Ni-Co (oxy)hydroxide nanowire-supported nanoflake arrays
      and their application in supercapacitors.
AB  - Three-dimensional (3D) hybrid nanostructured arrays grown on a flexible substrate
      have recently attracted great attention owing to their potential application as
      supercapacitor electrodes in portable and wearable electronic devices. Here, we
      report an in situ conversion of Ni-Co active electrode materials for the
      fabrication of high-performance electrodes. Ni-Co carbonate hydroxide nanowire
      arrays on carbon cloth were initially synthesized via a hydrothermal method, and
      they were gradually converted to Ni-Co (oxy)hydroxide nanowire-supported
      nanoflake arrays after soaking in an alkaline solution. The evolution of the
      supercapacitor performance of the soaked electrode was investigated in detail.
      The areal capacitance increases from 281 mF cm-2 at 1 mA cm-2 to 3710 and 3900 mF
      cm-2 after soaking for 36 h and 48 h, respectively. More interestingly, the
      electrode also shows an increased capacitance with charge/discharge cycles due to
      the long-time soaking in KOH solution, suggesting novel cycling durability. The
      enhancement in capacitive performance should be related to the formation of a
      unique nanowire-supported nanoflake array architecture, which controls the
      agglomeration of nanoflakes, making them fully activated. As a result, the facile
      in situ fabrication of the hybrid architectural design in this study provides a
      new approach to fabricate high-performance Ni/Co based hydroxide nanostructure
      arrays for next-generation energy storage devices.

PMID- 27714060
TI  - Serum metabolomics of Indian women with polycystic ovary syndrome using 1H NMR
      coupled with a pattern recognition approach.
AB  - Polycystic ovary syndrome (PCOS) is one of the most commonly occurring metabolic
      and endocrinological disorders affecting women of reproductive age. Metabolomics
      is an emerging field that holds promise in understanding disease pathophysiology.
      Recently, a few metabolomics based studies have been attempted in PCOS patients;
      however, none of them have included patients from the Indian population. The main
      objective of this study was to investigate the serum metabolomic profile of
      Indian women with PCOS and compare them with controls. Proton nuclear magnetic
      resonance (1H NMR) was used to first identify the differentially expressed
      metabolites among women with PCOS from the Eastern region of India during the
      discovery phase and further validated in a separate cohort of PCOS and control
      subjects. Multivariate analysis of the binned spectra indicated 16 dysregulated
      bins in the sera of these women with PCOS. Out of these 16 bins, 13 identified
      bins corresponded to 12 metabolites including 8 amino acids and 4 energy
      metabolites. Amongst the amino acids, alanine, valine, leucine and threonine and
      amongst the energy metabolites, lactate and acetate were observed to be
      significantly up-regulated in women with PCOS when compared with controls. The
      remaining 4 amino acids, l-glutamine, proline, glutamate and histidine were down
      regulated along with 2 energy metabolites: glucose and 3-hydroxybutyric acid. Our
      findings showed dysregulations in the expression of different metabolites in the
      serum of women with PCOS suggesting the involvement of multiple pathways
      including amino acid metabolism, carbohydrate/lipid metabolism, purine and
      pyrimidine metabolism and protein synthesis.

PMID- 27714061
TI  - Constructing bulk defective perovskite SrTiO3 nanocubes for high performance
      photocatalysts.
AB  - Defects (Ti3+ or oxygen vacancies) have been demonstrated to promote the charge
      separation process in TiO2 based photocatalysts. Particularly, the bulk defects
      within a certain concentration can give a great enhancement for both light
      absorption and charge separation efficiency. In this report, we explored a one
      step molten salts route to synthesize SrTiO3 nanocubes with bulk defects (Ti3+
      doped) by using SrCO3 as a Sr source, and TiO2 and Ti powder as Ti sources. The
      amount of defects can be tuned by changing the molar ratio of Ti/TiO2. The
      corresponding bandgap of SrTiO3 can be changed from 3.29 to 2.73 eV with the
      increase of defects. X-ray diffraction and electron microscopy disclose that
      SrTiO3 is highly crystalline and has a cubic morphology. X-ray photoelectron
      spectroscopy and electron paramagnetic resonance indicate that the as-prepared
      SrTiO3 is close to the Ti3+ doped SrTiO3. Surface photovoltage spectroscopy (SPS)
      and field-induced SPS confirm that Ti3+ doping in the SrTiO3 turns it from an n
      type semiconductor to p-type. The SrTiO3 with an optimal amount of defects
      exhibits highly enhanced photocatalytic performance. An excess amount of defects
      results in a weak SPS response and photocatalytic performance.

PMID- 27714062
TI  - Direct real-time detection of single proteins using silicon nanowire-based
      electrical circuits.
AB  - We present an efficient strategy through surface functionalization to build a
      single silicon nanowire field-effect transistor-based biosensor that is capable
      of directly detecting protein adsorption/desorption at the single-event level.
      The step-wise signals in real-time detection of His-tag F1-ATPases demonstrate a
      promising electrical biosensing approach with single-molecule sensitivity, thus
      opening up new opportunities for studying single-molecule biophysics in broad
      biological systems.

PMID- 27714063
TI  - Analysis of the distribution of organic compounds and drugs between biological
      tissues in the framework of solute partitioning in aqueous two-phase systems.
AB  - Partition coefficients of non-ionic essentially nonpolar compounds between air
      and rat biological tissues and between blood and other tissues were examined and
      found to be linearly interrelated according to the previously established
      equation for partition coefficients of solutes in aqueous two-phase systems: log
      Kblood-tissue-1 = k0 + k1 log Kblood-tissue-2 + k2 log Kblood-tissue-3, where k0,
      k1, and k2 are constants. Analysis of partition coefficients of amphiphilic and
      ionizable drugs between blood and different tissues in rats in vivo showed that
      the above relationship holds for the blood-tissue partition coefficients of these
      compounds as well. The data obtained indicate that distribution of organic
      compounds between different biological tissues may be considered in the framework
      of solute partitioning in aqueous two-phase systems, and imply that aqueous media
      in different tissues have different solvent properties, and compound-water
      interactions in these media may respond to different environments governed by the
      tissue composition.

PMID- 27714064
TI  - Amaryllidaceae and Sceletium alkaloids.
AB  - Covering: July 2012 to June 2015. Previous review: Nat. Prod. Rep., 2013, 30, 849
      868The latest progress on the isolation, identification, biological activity and
      synthetic studies of the structurally diverse alkaloids from plants of family
      Amaryllidaceae has been summarized in this review. In addition, the structurally
      related alkaloids isolated from Sceletium species were discussed as well.

PMID- 27714065
TI  - Contact-dominated transport in carbon nanotube thin films: toward large-scale
      fabrication of high performance photovoltaic devices.
AB  - Semiconducting single-walled carbon nanotubes (s-SWCNTs) have been widely
      regarded as potential channel materials for not only replacing silicon to extend
      Moore's law but also for building high performance optoelectronic devices. To
      realize these goals, high quality s-SWCNTs and contacts are needed to outperform
      devices based on traditional materials such as silicon. For a high quality
      conducting or active channel, the ideal CNTs consist of a pure s-SWCNTs array
      with a confined pitch of less than 10 nm via e.g., chemical vapor deposition
      (CVD) methods, although this has not been realized experimentally. On the other
      hand, significant progress has been made on solution-processed CNTs. However,
      only network and low performance optoelectronic devices have been realized. In
      this study, we systematically studied the performance of devices using solution
      processed CNT films with different s-SWCNT purity, with particular emphasis being
      placed on disentangling those metallic-CNTs (m-CNTs)-dominated low performance
      and contacts-dominated high performance devices. We demonstrated that using high
      purity s-SWCNTs allowed for the construction of high performance diodes via a
      doping-free method. These diodes behave similarly to those based on individual
      CVD-grown s-CNTs, resulting in 250 mV photovoltage for a typical single diode and
      more than 4.35 V for cascading cells using the virtual contact technique and thus
      paving the way for large scale fabrication of higher performance photovoltaic
      devices using readily available solution processed CNTs.

PMID- 27714066
TI  - A nanoparticle-based thermo-dynamic aptasensor for small molecule detection.
AB  - Small molecules (MW < 1000 Da) represent a large class of biomarkers of interest.
      Recently, a new class of biosensors has been emerging thanks to the recognition
      properties of aptamers, short DNA or RNA single strands, selected against such
      small molecular targets. Among them, an adenosine-specific aptamer has been
      largely described and used due to its remarkable affinity to this small target
      (KD = 6 MUM). In this paper, we achieved the proof-of-principle of an aptasensor
      based on the thermodynamic follow-up of adenosine binding with engineered split
      aptamer sequences. The detection is carried out by surface plasmon resonance
      imaging of split-aptamer micro-arrays, while signal amplification is ensured by
      gold nanoparticles (AuNPs). This original approach based on DNA sequence
      engineering and AuNP conjugation enabled us to reach limits of detection (LOD)
      200 times lower than the KD measured in solution with the native aptamer (LOD =
      30 nM).

PMID- 27714067
TI  - Synthesis, self-assembly, and immunological activity of alpha-galactose
      functionalized dendron-lipid amphiphiles.
AB  - Nanoassemblies presenting multivalent displays of biologically active
      carbohydrates are of significant interest for a wide array of biomedical
      applications ranging from drug delivery to immunotherapy. In this study,
      glycodendron-lipid hybrids were developed as a new and tunable class of dendritic
      amphiphiles. A modular synthesis was used to prepare dendron-lipid hybrids
      comprising distearylglycerol and 0 through 4th generation polyester dendrons with
      peripheral protected amines. Following deprotection of the amines, an
      isothiocyanate derivative of C-linked alpha-galactose (alpha-Gal) was conjugated
      to the dendron peripheries, affording amphiphiles with 1 to 16 alpha-Gal
      moieties. Self-assembly in water through a solvent exchange process resulted in
      vesicles for the 0 through 2nd generation systems and micelles for the 3rd and
      4th generation systems. The critical aggregation concentrations decreased with
      increasing dendron generation, suggesting that the effects of increasing molar
      mass dominated over the effects of increasing the hydrophilic weight fraction.
      The binding of the assemblies to Griffonia simplicifolia Lectin I (GSL 1), a
      protein with specificity for alpha-Gal was studied by quantifying the binding of
      fluorescently labeled assemblies to GSL 1-coated beads. It was found that binding
      was enhanced for amphiphiles containing higher generation dendrons. Despite their
      substantial structural differences with the natural ligands for the CD1d
      receptor, the glycodendron-lipid hybrids were capable of stimulating invariant
      natural killer T (iNKT) cells, a class of innate-like T cells that recognize
      lipid and glycolipid antigens presented by CD1d and that are implicated in a wide
      range of diseases and conditions including but not limited to infectious
      diseases, diabetes and cancer.

PMID- 27714068
TI  - A systems biology approach reveals new endoplasmic reticulum-associated targets
      for the correction of the ATP7B mutant causing Wilson disease.
AB  - Copper (Cu) is an important trace element required for the activity of essential
      enzymes. However, excess Cu compromises the redox balance in cells and tissues
      causing serious toxicity. The process of disposal of excess Cu from organisms
      relies on the activity of Cu-transporting ATPase ATP7B. ATP7B is mainly expressed
      in liver hepatocytes where it sequesters the potentially toxic metal and mediates
      its excretion into the bile. Mutations in the ATP7B gene cause Wilson disease
      (WD), which is characterized by the accumulation of toxic Cu in the liver due to
      the scarce expression of ATP7B as well as the failure of ATP7B mutants to pump Cu
      and/or traffic to the Cu-excretion sites. The most frequent ATP7B mutant, H1069Q,
      still presents a significant Cu-transporting activity, but undergoes retention
      within the endoplasmic reticulum (ER) where the mutant is rapidly degraded.
      Expression of this ATP7B mutant has been recently reported to activate the p38
      and JNK stress kinase pathways, which, in turn, trigger quality control
      mechanisms leading to the arrest of ATP7B-H1069Q in the ER and to the
      acceleration of its degradation. However, the main molecular players operating in
      these p38/JNK-dependent ER quality control pathways remain to be discovered. By
      using a combination of RNAseq, bioinformatics and RNAi approaches, we found a
      cluster of ER quality control genes whose expression is controlled by p38 and JNK
      and is required for the efficient retention of the ATP7B-H1069Q mutant in the ER.
      Silencing these genes reduced the accumulation of the ATP7B mutant in the ER and
      facilitated the mutant sorting and export to the Golgi and post-Golgi copper
      excretion sites. In sum, our findings reveal the ER-associated genes that could
      be utilized for the correction of ATP7B mutants and, hence, for the normalization
      of Cu homeostasis in Wilson disease.

PMID- 27714069
TI  - Hidden symmetry of small spherical viruses and organization principles in
      "anomalous" and double-shelled capsid nanoassemblies.
AB  - We propose the principles of structural organization in spherical nanoassemblies
      with icosahedral symmetry constituted by asymmetric protein molecules. The
      approach modifies the paradigmatic geometrical Caspar and Klug (CK) model of
      icosahedral viral capsids and demonstrates the common origin of both the
      "anomalous" and conventional capsid structures. In contrast to all previous
      models of "anomalous" viral capsids the proposed modified model conserves the
      basic structural principles of the CK approach and reveals the common hidden
      symmetry underlying all small viral shells. We demonstrate the common genesis of
      the "anomalous" and conventional capsids and explain their structures in the same
      frame. The organization principles are derived from the group theory analysis of
      the positional order on the spherical surface. The relationship between the
      modified CK geometrical model and the theory of two-dimensional spherical
      crystallization is discussed. We also apply the proposed approach to complex
      double-shelled capsids and capsids with protruding knob-like proteins. The
      introduced notion of commensurability for the concentric nanoshells explains the
      peculiarities of their organization and helps to predict analogous, but yet
      undiscovered, double-shelled viral capsid nanostructures.

PMID- 27714070
TI  - CuGaS2-ZnS p-n nanoheterostructures: a promising visible light photo-catalyst for
      water-splitting hydrogen production.
AB  - In this work, novel CuGaS2-ZnS p-n type semiconductor nanoheterostructures were
      synthesized by a solution route, and demonstrated experimentally to be a very
      promising visible light active photo-catalyst for water-splitting hydrogen
      production. The construction of CuGaS2-ZnS heterostructures follows a multi-step
      strategy, employing Cu1.94S nanocrystals first as catalytic assistants for the
      hetero-growth of ZnS on their surfaces, and then as sacrificial seeds for the
      formation of CuGaS2. Excitingly, attributed to the efficient charge separation
      introduced by the p-n heterojunctions, the hydrogen production ability of the
      CuGaS2-ZnS nanoheterostructures under visible light irradiation is 15 times
      higher than that of the CuGaS2 component, and comparable to that of the CdS
      nanophase which is currently regarded as one of the most active visible photo
      catalysts for hydrogen generation.

PMID- 27714071
TI  - Artificial hydrolase based on carbon nanotubes conjugated with peptides.
AB  - An artificial enzyme was constructed by attaching short peptides with active
      sites (SHELKLKLKL, WLKLKLKL) onto carbon nanotubes (CNT). It was found that the
      combination of SHE amino acids was essential to form a catalytic triad. W was
      also incorporated into this artificial enzyme and acted as a substrate binding
      site, thus producing an enzyme model with synergism of 67.7% catalytic groups and
      32.3% binding groups, CNT-(SHE/W)2:1-LKLKLKL. When the peptide SHELKLKLKL was
      attached with the catalytic triad site close to the surface of CNT, the composite
      had higher activity than a leucine-attached system terminated with the catalytic
      triad site, suggesting that CNT not only served as a platform for attaching
      active amino acids, but also created a hydrophobic microenvironment and
      facilitated the proton transfer process to enhance the catalytic activity. The
      artificial enzyme exhibited Michaelis-Menten behaviour, indicating that it was
      indeed a mimic of the corresponding natural enzyme. This work showed that a well
      designed combination of CNT and short peptides containing active sites can mimic
      a natural enzyme.

PMID- 27714072
TI  - Dynamic visualization of photothermal heating by gold nanocages using
      thermoresponsive elastin like polypeptides.
AB  - Understanding how plasmonic nanoparticles collectively generate heat upon
      exposure to light and thus increase the local temperature of the surrounding
      medium is critical for many applications such as plasmon-assisted microfluidics,
      plasmonic tweezers, and photothermal cancer therapy. Reliable temperature
      manipulation requires the capability to spatially and dynamically analyze local
      temperature profiles as a function of nanoparticle concentration and laser
      intensity. In this work, we present a novel method for visualization of local
      temperature increase using elastin-like polypeptides (ELP). We also propose a
      robust algorithm that allows the construction of reliable calibration curves
      using known boundary conditions and Boltzmann sigmoid fit applied to the ELP
      solution's temperature-absorption transfer function. Using this technique, for
      the first time, we successfully demonstrated how surface and volume distribution
      of the nano-heaters affect collective heat generation. This approach allows the
      visualization of dynamic 2D-temperature profiles and simultaneously enables the
      measurement of specific temperature at any point in a 2D-map. The experimental
      setup is compatible with conventional optical microscopy and requires no
      specialized hardware or complex sample preparation. Finally, the real time
      visualization of plasmonic heating offers an opportunity to control outcomes of
      thermo-plasmonics which enables a myriad of practical applications.

PMID- 27714073
TI  - Constructing bifunctional nanoparticles for dual targeting: improved grafting and
      surface recognition assessment of multiple ligand nanoparticles.
AB  - Nanoparticles (NPs) functionalized with two active targeting ligands have been
      proposed in drug delivery for their promising capability to stimulate different
      pathways with one object. Due to the multivalency, the construction and analysis
      of the effective surface of such bifunctional nanoparticles, however, is
      significantly more complex than for nanoparticles bearing only one ligand. Here,
      we optimize construction and analysis of bifunctional NPs containing recognizable
      combinations of human serum albumin (HSA), transferrin (Tf), and epidermal growth
      factor (EGF) on fluorescent silica NPs grafted via common polyethylene glycol
      (PEG) linkers as a model system. Combined with an overall protein quantification,
      a mapping of exposed recognizable sequences using monoclonal antibodies
      conjugated to gold nanoparticles (AuNPs) or quantum dots (QDs) for enhanced
      spectroscopic and microscopic detection revealed that active protein sequences
      can be one to two orders of magnitude lower than overall conjugated proteins
      while possessing specific cellular recognition. In addition, we found that common
      conjugation strategies lead to a large excess of non-specifically compared to
      covalently bound ligands and instabilities that may impact targeting. These can
      be avoided by certain synthetic conditions presented here for effective
      exploitation of multivalent surfaces in nanomedicine.

PMID- 27714074
TI  - miR-186 regulates chemo-sensitivity to paclitaxel via targeting MAPT in non-small
      cell lung cancer (NSCLC).
AB  - miR-186 has been reported to be implicated in tumorigenesis and chemoresistance
      in a few cancer types. However, its role in regulating chemoresistance has not
      been investigated in non-small cell lung cancer (NSCLC). To examine the effects
      of miR-186 on chemosensitivity in NSCLC, an miR-186 mimic and inhibitor were
      transfected, followed by CellTiter-Glo(r) assay in NSCLC cell lines. Western blot
      and luciferase assay were performed to investigate the direct targeting of miR
      186. A xenograft mouse model was used to examine the in vivo chemosensitizing
      function of miR-186. We found that overexpression of miR-186 sensitized A549 and
      H1299 cells to paclitaxel, whereas inhibition of miR-186 conferred resistance in
      these cells. MAPT was the direct target of miR-186 which was required for the
      regulatory role of miR-186 in chemoresistance. This chemosensitizing function was
      partially due to the induction of the p53 mediated apoptotic pathway. The miR-186
      mimic enhanced the tumor growth inhibitory effects of paclitaxel in A549
      xenografts. In addition, miR-186 was found to be down-regulated in NSCLC patients
      who were chemoresistant and this down-regulation was associated with poor
      survival. Taken together, our study demonstrated that miR-186 regulates the
      chemoresistance of NSCLC cells by modulating the MAPT expression level both in
      vitro and in vivo. miR-186 may represent a new therapeutic target for the
      improvement of the clinical outcome in NSCLC.

PMID- 27714075
TI  - Correction: Hot off the press.
AB  - Correction for 'Hot off the press' by Robert A. Hill et al., Nat. Prod. Rep.,
      2016, DOI: 10.1039/c6np90039a.

PMID- 27714076
TI  - Nanoengineering neural stem cells on biomimetic substrates using magnetofection
      technology.
AB  - Tissue engineering studies are witnessing a major paradigm shift to cell culture
      on biomimetic materials that replicate native tissue features from which the
      cells are derived. Few studies have been performed in this regard for neural
      cells, particularly in nanomedicine. For example, platforms such as magnetic
      nanoparticles (MNPs) have proven efficient as multifunctional tools for cell
      tracking and genetic engineering of neural transplant populations. However, as
      far as we are aware, all current studies have been conducted using neural cells
      propagated on non-neuromimetic substrates that fail to represent the mechano
      elastic properties of brain and spinal cord microenvironments. Accordingly, it
      can be predicted that such data is of less translational and physiological
      relevance than that derived from cells grown in neuromimetic environments.
      Therefore, we have performed the first test of magnetofection technology
      (enhancing MNP delivery using applied magnetic fields with significant potential
      for therapeutic application) and its utility in genetically engineering neural
      stem cells (NSCs; a population of high clinical relevance) propagated in
      biomimetic hydrogels. We demonstrate magnetic field application safely enhances
      MNP mediated transfection of NSCs grown as 3D spheroid structures in collagen
      which more closely replicates the intrinsic mechanical and structural properties
      of neural tissue than routinely used hard substrates. Further, as it is well
      known that MNP uptake is mediated by endocytosis we also investigated NSC
      membrane activity grown on both soft and hard substrates. Using high resolution
      scanning electron microscopy we were able to prove that NSCs display lower levels
      of membrane activity on soft substrates compared to hard, a finding which could
      have particular impact on MNP mediated engineering strategies of cells propagated
      in physiologically relevant systems.

PMID- 27714077
TI  - Monolayer graphene sensing enabled by the strong Fano-resonant metasurface.
AB  - Recent advances in graphene photonics reveal promising applications in the
      technologically important terahertz spectrum, where graphene-based active
      terahertz metamaterial modulators have been experimentally demonstrated. However,
      the sensitivity of the atomically thin graphene monolayer towards sharp Fano
      resonant terahertz metasurfaces remains unexplored. Here, we demonstrate thin
      film sensing of the graphene monolayer with a high quality factor terahertz Fano
      resonance in metasurfaces consisting of a two-dimensional array of asymmetric
      resonators. A drastic change in the transmission amplitude of the Fano resonance
      was observed due to strong interactions between the monolayer graphene and the
      tightly confined electric fields in the capacitive gaps of the Fano resonator.
      The deep-subwavelength sensing of the atomically thin monolayer graphene further
      highlights the extreme sensitivity of the resonant electric field excited at the
      dark Fano resonance, allowing the detection of an analyte that is lambda/1 000
      000 thinner than the free space wavelength.

PMID- 27714078
TI  - Advances in the synthesis of glycosidic macrolides: clavosolides A-D and
      cyanolide A.
AB  - Covering: 2005 to 2016Clavosolides A-D and cyanolide A are glycosidic macrolides
      and represent a new family of marine natural products. They possess a number of
      unusual structural features and have attracted considerable interest from the
      synthetic community. This review presents a comprehensive survey of all aspects
      of the clavosolides A-D and cyanolide A. Specific topics include isolation,
      structure determination, biological activity, and synthetic approaches.

PMID- 27714079
TI  - High-performance flexible ZnO nanorod UV photodetectors with a network-structured
      Cu nanowire electrode.
AB  - In this work, vertically aligned zinc oxide (ZnO) nanorod (NR)-based flexible
      ultraviolet (UV) photodetectors were successfully fabricated on a polyimide (PI)
      substrate with a copper (Cu) nanowire (NW) electrode. To enhance the flexibility
      and sensing properties, the entangled networks of Cu NWs were applied to UV
      photodetectors as a flexible electrode. Here, Cu NWs have a high conductivity
      with a low cost compared to other metals to achieve a Schottky contact with ZnO
      NRs. Moreover, because of forming a network structure, the surface of the sensing
      material has a large contact area with oxygen molecules, resulting in a faster
      response time. The Cu NW electrode exhibited a high optical transmittance of 90%,
      a considerable sheet resistance of 50 Omega sq-1, and a work function of 5.12 eV.
      Consequentially, the fabricated UV photodetector with Cu NW electrodes showed
      excellent UV sensing properties with a very fast rising time of 0.7 s and a decay
      time of 1.9 s in the dark and under UV illumination (365 nm, 0.40 mW cm-2) at a
      reverse bias of -2.0 V. Furthermore, during the bending test at a radius of
      curvature of 5 mm, the flexible ZnO NR UV photodetectors with Cu NW electrodes
      exhibited almost unchanged UV sensing properties even after 5000 cycles.

PMID- 27714080
TI  - Tracking of photochemical Ostwald ripening of nanoparticles through voltammetric
      atom counting.
AB  - We report the tracking of atom count in individual nanoparticles during
      photochemical Ostwald ripening. The nano-impact technique, in conjunction with UV
      Vis and TEM analysis, is used to follow the photochemical formation of silver
      nano-prisms from spherical seed particles. A mechanism of photochemical Ostwald
      ripening is deduced and key growth stages are identified.

PMID- 27714081
TI  - Protein clustering in chemically stressed HeLa cells studied by infrared
      nanospectroscopy.
AB  - Photo-Thermal Induced Resonance (PTIR) nanospectroscopy, tuned towards amide-I
      absorption, was used to study the distribution of proteic material in 34
      different HeLa cells, of which 18 were chemically stressed by oxidative stress
      with Na3AsO3. The cell nucleus was found to provide a weaker amide-I signal than
      the surrounding cytoplasm, while the strongest PTIR signal comes from the
      perinuclear region. AFM topography shows that the cells exposed to oxidative
      stress undergo a volume reduction with respect to the control cells, through an
      accumulation of the proteic material around and above the nucleus. This is
      confirmed by the PTIR maps of the cytoplasm, where the pixels providing a high
      amide-I signal were identified with a space resolution of ~300 * 300 nm. By
      analyzing their distribution with two different statistical procedures we found
      that the probability to find protein clusters smaller than 0.6 MUm in the
      cytoplasm of stressed HeLa cells is higher by 35% than in the control cells.
      These results indicate that it is possible to study proteic clustering within
      single cells by label-free optical nanospectroscopy.

PMID- 27714082
TI  - A redox-responsive mesoporous silica nanoparticle with a therapeutic peptide
      shell for tumor targeting synergistic therapy.
AB  - In this study, we report a novel redox-responsive mesoporous silica nanoparticle
      (MSN)-based nanocarrier, capping with a therapeutic peptide ((RGDWWW)2KC)
      containing a RGD target motif, for tumor targeting synergistic therapy, which is
      designated as TTSTMSN. The MSN was decorated with a tumor-targeting therapeutic
      peptide as a potential gatekeeper. The two branched peptides containing rich
      tryptophans allowed the pores to be blocked via pi-pi stacking and hydrophobic
      interactions. Once the drug loaded nanoparticles were taken up by the cancer
      cells through integrin-mediated endocytosis, the therapeutic peptide capping
      shells on the surface of MSNs were released, inducing the loaded drug to diffuse
      into the cytoplasm after breaking of the disulfide bonds, triggered by the high
      concentration of glutathione (GSH) in cancer cells. At the same time, the falling
      therapeutic rich tryptophans in the branched chains interacted with DNA due to
      the indole rings, leading to disturbance of the DNA structure through the strong
      pi interactions and causing cell apoptosis. There is no such report on capping of
      drug loaded porous silica with a therapeutic peptide shell, co-delivering an
      anticancer drug and therapeutic agent for tumor targeting synergistic therapy,
      which will have great potential in developing multifunctional nanocarriers based
      on therapeutic peptides for synergistic treatment.

PMID- 27714083
TI  - Hydrogen bonding vs. molecule-surface interactions in 2D self-assembly of
      [C60]fullerenecarboxylic acids.
AB  - The adsorption of C60-malonic derivatives C61(CO2H)2 and C66(CO2H)12 on Au(111)
      and a pentafluorobenzenethiol-modified Au substrate (PFBT@Au) has been
      investigated using scanning tunneling microscopy (STM) at a liquid-solid
      interface. Monofunctionalized C61(CO2H)2 forms a hexagonal close-packed overlayer
      on Au(111) and individual aligned dimers on PFBT@Au(111). The difference is
      attributed to the nature of the substrateC61(CO2H)2 interaction (isotropic pi-Au
      bonding vs. anisotropic PFBTCOOH interactions). Surprisingly, in both cases, the
      directionality of the COOHCOOH motif is compromised in favor of synergistic van
      der Waals/H bonding interactions. Such van der Waals contacts are geometrically
      unfeasible in hexafunctionalized C66(CO2H)12 and its assembly on Au(111) leads to
      a 2D molecular network controlled exclusively by H bonding. For both molecules,
      the "free" CO2H groups on the monolayer surface can engage in out-of-plane H
      bonding interaction resulting in the epitaxial growth of subsequent molecular
      layers.

PMID- 27714084
TI  - Mammalian copper biology: hitting the pause button in celebration of three
      pioneers and four decades of discovery.

PMID- 27714085
TI  - Solid-state colloidal CuInS2 quantum dot solar cells enabled by bulk
      heterojunctions.
AB  - Colloidal copper indium sulfide (CIS) nanocrystals (NCs) are Pb- and Cd-free
      alternatives for use as absorbers in quantum dot solar cells. In a heterojunction
      with TiO2, non-annealed ligand-exchanged CIS NCs form solar cells yielding a
      meager power conversion efficiency (PCE) of 0.15%, with photocurrents plummeting
      far below predicted values from absorption. Decreasing the amount of zinc during
      post-treatment leads to improved mobility but marginal improvement in device
      performance (PCE = 0.30%). By incorporating CIS into a porous TiO2 network, we
      saw an overall drastic improvement in device performance, reaching a PCE of
      1.16%, mainly from an increase in short circuit current density (Jsc) and fill
      factor (FF) and a 10-fold increase in internal quantum efficiency (IQE). We have
      determined that by moving from a bilayer to a bulk heterojunction architecture,
      we have reduced the trap-assisted recombination as seen in changes in the
      ideality factor, the intensity dependence of the photocurrent and transient
      photocurrent (TPC) and photovoltage (TPV) characteristics.

PMID- 27714086
TI  - 1D Ni-Co oxide and sulfide nanoarray/carbon aerogel hybrid nanostructures for
      asymmetric supercapacitors with high energy density and excellent cycling
      stability.
AB  - The fabrication of supercapacitor electrodes with high energy density and
      excellent cycling stability is still a great challenge. A carbon aerogel,
      possessing a hierarchical porous structure, high specific surface area and
      electrical conductivity, is an ideal backbone to support transition metal oxides
      and bring hope to prepare electrodes with high energy density and excellent
      cycling stability. Therefore, NiCo2S4 nanotube array/carbon aerogel and NiCo2O4
      nanoneedle array/carbon aerogel hybrid supercapacitor electrode materials were
      synthesized by assembling Ni-Co precursor needle arrays on the surface of the
      channel walls of hierarchical porous carbon aerogels derived from chitosan in
      this study. The 1D nanostructures grow on the channel surface of the carbon
      aerogel vertically and tightly, contributing to the enhanced electrochemical
      performance with ultrahigh energy density. The energy density of NiCo2S4 nanotube
      array/carbon aerogel and NiCo2O4 nanoneedle array/carbon aerogel hybrid
      asymmetric supercapacitors can reach up to 55.3 Wh kg-1 and 47.5 Wh kg-1 at a
      power density of 400 W kg-1, respectively. These asymmetric devices also
      displayed excellent cycling stability with a capacitance retention of about 96.6%
      and 92% over 5000 cycles.

PMID- 27714087
TI  - A review of recent developments in rechargeable lithium-sulfur batteries.
AB  - The research and development of advanced energy-storage systems must meet a large
      number of requirements, including high energy density, natural abundance of the
      raw material, low cost and environmental friendliness, and particularly
      reasonable safety. As the demands of high-performance batteries are continuously
      increasing, with large-scale energy storage systems and electric mobility
      equipment, lithium-sulfur batteries have become an attractive candidate for the
      new generation of high-performance batteries due to their high theoretical
      capacity (1675 mA h g-1) and energy density (2600 Wh kg-1). However, rapid
      capacity attenuation with poor cycle and rate performances make the batteries far
      from ideal with respect to real commercial applications. Outstanding
      breakthroughs and achievements have been made to alleviate these problems in the
      past ten years. This paper presents an overview of recent advances in lithium
      sulfur battery research. We cover the research and development to date on various
      components of lithium-sulfur batteries, including cathodes, binders, separators,
      electrolytes, anodes, collectors, and some novel cell configurations. The current
      trends in materials selection for batteries are reviewed and various choices of
      cathode, binder, electrolyte, separator, anode, and collector materials are
      discussed. The current challenges associated with the use of batteries and their
      materials selection are listed and future perspectives for this class of battery
      are also discussed.

PMID- 27714088
TI  - An ultrasensitive SERS sensor for simultaneous detection of multiple cancer
      related miRNAs.
AB  - Simultaneous detection of multiple trace cancer associated serum miRNA biomarkers
      is considered as a feasible method for early cancer screening and diagnosis. In
      the present work, an ultrasensitive SERS sensor was prepared based on an Ag
      nanorod array SERS substrate by assembling special hairpin-shaped molecular
      beacons (MBs) for the detection of multiple lung cancer-related miRNA biomarkers.
      The portable SERS sensor exhibits excellent performance for the qualitative and
      quantitative detection of miRNAs, with advantages of ultra-sensitivity, good
      specificity, uniformity, reproducibility and stability, as well as remarkable
      reusability. By monitoring the SERS signal quenching of the MBs in the presence
      of target miRNA biomarkers, three lung cancer related-miRNAs (miRNA-21, miRNA
      486, and miRNA-375) in buffer and human serum were simultaneously assayed using
      the SERS sensor array, and the limits of detection of the three miRNAs in human
      serum are 393 aM, 176 aM, and 144 aM, respectively. The reliable results
      demonstrate that the proposed SERS sensor array can be a promising candidate with
      great potential for the screening and clinical diagnosis of cancer in the early
      stage.

PMID- 27714089
TI  - Field emission and anode etching during formation of length-controlled nanogaps
      in electrical breakdown of horizontally aligned single-walled carbon nanotubes.
AB  - We observe field emission between nanogaps and voltage-driven gap extension of
      single-walled carbon nanotubes (SWNTs) on substrates during the electrical
      breakdown process. Experimental results show that the gap size is dependent on
      the applied voltage and humidity, which indicates high controllability of the gap
      size by appropriate adjustment of these parameters in accordance with the
      application. We propose a mechanism for the gap formation during electrical
      breakdown as follows. After small gaps are formed by Joule heating-induced
      oxidation, SWNTs on the anode side are electrochemically etched due to physically
      adsorbed water from the air and the enhanced electric field at the SWNT tips.
      Field emission is measured in a vacuum as a possible mechanism for charge
      transfer at SWNT gaps. The relationship between the field enhancement factor and
      geometric features of SWNTs explains both the voltage dependence of the extended
      gap size and the field emission properties of the SWNT gaps. In addition, the
      similar field-induced etching can cause damage to adjacent SWNTs, which possibly
      deteriorates the selectivity for cutting metallic pathways in the presence of
      water vapor.

PMID- 27714090
TI  - The Mendeleev-Meyer force project.
AB  - Here we present the Mendeleev-Meyer Force Project which aims at tabulating all
      materials and substances in a fashion similar to the periodic table. The goal is
      to group and tabulate substances using nanoscale force footprints rather than
      atomic number or electronic configuration as in the periodic table. The process
      is divided into: (1) acquiring nanoscale force data from materials, (2)
      parameterizing the raw data into standardized input features to generate a
      library, (3) feeding the standardized library into an algorithm to generate,
      enhance or exploit a model to identify a material or property. We propose
      producing databases mimicking the Materials Genome Initiative, the Medical
      Literature Analysis and Retrieval System Online (MEDLARS) or the PRoteomics
      IDEntifications database (PRIDE) and making these searchable online via search
      engines mimicking Pubmed or the PRIDE web interface. A prototype exploiting deep
      learning algorithms, i.e. multilayer neural networks, is presented.

PMID- 27714091
TI  - Highly aligned core-shell structured nanofibers for promoting phenotypic
      expression of vSMCs for vascular regeneration.
AB  - This study was designed to assess the efficacy of hyaluronan (HA) functionalized
      well-aligned nanofibers of poly-l-lactic acid (PLLA) in modulating the phenotypic
      expression of vascular smooth muscle cells (vSMCs) for blood vessel regeneration.
      Highly aligned HA/PLLA nanofibers in core-shell structure were prepared using a
      novel stable jet electrospinning approach. Formation of a thin HA-coating layer
      atop each PLLA nanofiber surface endowed the uni-directionally oriented fibrous
      mats with increased anisotropic wettability and mechanical compliance. The
      HA/PLLA nanofibers significantly promoted vSMC to elongation, orientation, and
      proliferation, and also up-regulated the expression of contractile genes/proteins
      (e.g., alpha-SMA, SM-MHC) as well as the synthesis of elastin. Six weeks of in
      vivo scaffold replacement of rabbit carotid arteries showed that vascular
      conduits made of circumferentially aligned HA/PLLA nanofibers could maintain
      patency and promoted oriented vSMC regeneration, lumen endothelialization, and
      capillary formation. This study demonstrated the synergistic effects of
      nanotopographical and biochemical cues in one biomimetic scaffold design for
      efficacious vascular regeneration.

PMID- 27714092
TI  - Magnesium ions in yeast: setting free the metabolism from glucose catabolite
      repression.
AB  - In a recent work we showed that magnesium (MgII) plays an important role in
      industrial ethanol production, overcoming the negative effect of the excess of
      minerals, particularly copper, present in sugarcane juice, with a consequent
      increase in ethanol yield. This cation has been reported to be involved in
      several steps of yeast metabolism, acting mainly as a co-factor of several
      enzymes of fermentation metabolism and protecting yeast cells from stressful
      conditions. However, despite many physiological investigations, its effect in the
      molecular mechanisms that control such metabolic activities remains unclear and
      to date no information concerning its influence on gene expression has been
      provided. The present work took advantage of the DNA microarray technology to
      analyse the global gene expression in yeast cells upon fermentation in MgII
      supplemented medium. The results of the fermentation parameters confirmed the
      previous report on the increase in ethanol yield by MgII. Moreover, the gene
      expression data revealed an unexpected set of up-regulated genes currently
      assigned as being negatively-regulated by glucose, which belong to respiratory
      and energy metabolism, the stress response and the glyoxalate cycle. On the other
      hand, genes involved in ribosome biogenesis were down-regulated. Computational
      analysis provided evidence for a regulatory network commanded by key
      transcriptional factors that may be responsible for the biological action of MgII
      in yeast cells. In this scenario, MgII seems to act by reprogramming the yeast
      metabolism by releasing many genes from glucose catabolite repression with
      positive consequences for ethanol production and maintenance of cell viability.

PMID- 27714093
TI  - Carbon dot and BiVO4 quantum dot composites for overall water splitting via a two
      electron pathway.
AB  - Carbon dot and BiVO4 quantum dot composites (CDs/BiVO4 QDs) show a significantly
      improved photocatalytic activity and high stability for overall water splitting.
      By using 5% CDs/BiVO4 QDs as photocatalysts, the H2 evolution of 0.92 MUmol h-1,
      was achieved under solar light irradiation without any cocatalysts or sacrificial
      reagents, which is about 4 times that of BiVO4 QDs (0.21 MUmol h-1). Note that,
      for the CD/BiVO4 QD catalyst, the produced H2 and O2 are approximately equal to
      the stoichiometric ratio (H2 : O2 = 1.80 : 1), while that of BiVO4 QDs is
      nonstoichiometric (about only 0.06 : 1). In addition, the present water splitting
      occurs via a two-electron pathway and CDs and BiVO4 QDs served as the reduction
      and oxidation reaction active sites, respectively.

PMID- 27714094
TI  - Skin inspired fractal strain sensors using a copper nanowire and graphite
      microflake hybrid conductive network.
AB  - This work demonstrates a facile "paint-on" approach to fabricate highly
      stretchable and highly sensitive strain sensors by combining one-dimensional
      copper nanowire networks with two-dimensional graphite microflakes. This paint-on
      approach allows for the fabrication of electronic skin (e-skin) patches which can
      directly replicate with high fidelity the human skin surface they are on,
      regardless of the topological complexity. This leads to high accuracy for
      detecting biometric signals for applications in personalised wearable sensors.
      The copper nanowires contribute to high stretchability and the graphite flakes
      offer high sensitivity, and their hybrid coating offers the advantages of both.
      To understand the topological effects on the sensing performance, we utilized
      fractal shaped elastomeric substrates and systematically compared their
      stretchability and sensitivity. We could achieve a high stretchability of up to
      600% and a maximum gauge factor of 3000. Our simple yet efficient paint-on
      approach enabled facile fine-tuning of sensitivity/stretchability simply by
      adjusting ratios of 1D vs. 2D materials in the hybrid coating, and the
      topological structural designs. This capability leads to a wide range of
      biomedical sensors demonstrated here, including pulse sensors, prosthetic hands,
      and a wireless ankle motion sensor.

PMID- 27714095
TI  - Charge transfer in crystalline germanium/monolayer MoS2 heterostructures prepared
      by chemical vapor deposition.
AB  - Heterostructuring provides novel opportunities for exploring emergent phenomena
      and applications by developing designed properties beyond those of homogeneous
      materials. Advances in nanoscience enable the preparation of heterostructures
      formed incommensurate materials. Two-dimensional (2D) materials, such as graphene
      and transition metal dichalcogenides, are of particular interest due to their
      distinct physical characteristics. Recently, 2D/2D heterostructures have opened
      up new research areas. However, other heterostructures such as 2D/three
      dimensional (3D) materials have not been thoroughly studied yet although the
      growth of 3D materials on 2D materials creating 2D/3D heterostructures with
      exceptional carrier transport properties has been reported. Here we report a
      novel heterostructure composed of Ge and monolayer MoS2, prepared by chemical
      vapor deposition. A single crystalline Ge (110) thin film was grown on monolayer
      MoS2. The electrical characteristics of Ge and MoS2 in the Ge/MoS2
      heterostructure were remarkably different from those of isolated Ge and MoS2. The
      field-effect conductivity type of the monolayer MoS2 is converted from n-type to
      p-type by growth of the Ge thin film on top of it. Undoped Ge on MoS2 is highly
      conducting. The observations can be explained by charge transfer in the
      heterostructure as opposed to chemical doping via the incorporation of
      impurities, based on our first-principles calculations.

PMID- 27714096
TI  - Tunable nanoblock lasers and stretching sensors.
AB  - Reconfigurable, reliable, and robust nanolasers with wavelengths tunable in the
      telecommunication bands are currently being sought after for use as flexible
      light sources in photonic integrated circuits. Here, we propose and demonstrate
      tunable nanolasers based on 1D nanoblocks embedded within stretchable
      polydimethylsiloxane. Our lasers show a large wavelength tunability of 7.65 nm
      per 1% elongation. Moreover, this tunability is reconfigurable and reliable under
      repeated stretching/relaxation tests. By applying excessive stretching, wide
      wavelength tuning over a range of 80 nm (spanning the S, C, and L
      telecommunication bands) is successfully demonstrated. Furthermore, as a
      stretching sensor, an enhanced wavelength response to elongation of 9.9 nm per %
      is obtained via the signal differential from two nanoblock lasers positioned
      perpendicular to each other. The minimum detectable elongation is as small as
      0.056%. Nanoblock lasers can function as reliable tunable light sources in
      telecommunications and highly sensitive on-chip structural deformation sensors.

PMID- 27714097
TI  - Standalone anion- and co-doped titanium dioxide nanotubes for photocatalytic and
      photoelectrochemical solar-to-fuel conversion.
AB  - Several strategies are currently being investigated for conversion of incident
      sunlight into renewable sources of energy, and photocatalytic or
      photoelectrochemical production of solar fuels can provide an important
      alternative. Titanium dioxide (TiO2) has been heavily investigated as a material
      of choice due to its excellent optoelectronic properties and stability, and anion
      doping proposed as a pathway to improve light absorption as well as improving the
      efficiency of oxygen production. While several studies have used morphological
      tuning, elemental doping, and surface engineering in TiO2 to extend its
      absorption, there is a need to optimize simultaneously charge transport and
      improve interfacial chemical reaction kinetics. Here we show anion-doped
      (nitrogen, carbon) standalone TiO2 nanotube membranes that absorb visible light
      for the water-splitting reaction, using both wireless (photocatalysis) and wired
      (photoelectrochemical) solar-to-fuel conversion (STFC) cells. Using simulated
      solar radiation, we show generation of hydrogen as a solar fuel using visible
      light photocatalysis. Furthermore, using a model we elucidate detailed
      photophysics and photoelectrochemical properties of these nanotubes, and explain
      the kinetics of photogenerated charge carriers following light absorption. We
      show that while visible light induces a superlinear photoresponse for catalytic
      reduction and may benefit from higher incident light intensity, ultraviolet light
      shows a linear photoresponse and saturation with higher light flux due to
      trapping of photogenerated charges (mainly electrons). These results can have
      important implications for design of other metal-oxide membranes for solar fuel
      generation, and appropriate design of dopants and induced energy levels in these
      photocatalysts.

PMID- 27714098
TI  - Tuning the Fermi-level of TiO2 mesoporous layer by lanthanum doping towards
      efficient perovskite solar cells.
AB  - Tuning the band alignment is proved to be an effective way to facilitate carrier
      transportation and thus enhance the power conversion efficiency (PCE) of solar
      cells. Doping the compact layer with metal ions or modifying the interfaces among
      functional layers in perovskite solar cells (PSCs) can appreciably improve the
      PCE of PSCs. Inspired by the rare earth elemental doping of TiO2, which has
      witnessed the success in photocatalysis and dye-sensitized solar cells, we
      firstly demonstrated here that La3+ doping in the mesoporous TiO2 layer of a
      mesostructured PSC can tune its Fermi level and thus significantly enhance the
      device PCE. Systematic analysis reveals that doping La3+ into TiO2 raises the
      Fermi level of TiO2 through scavenging oxygen and inducing vacancies, which
      subsequently increases the open circuit voltage and the fill factor while
      reducing the series resistance of the PSC using La3+-doped TiO2 as a mesoporous
      layer. As a result, a PCE of 15.42% is achieved, which is appreciably higher than
      the PCE of a device with undoped TiO2 (12.11%).

PMID- 27714099
TI  - Three-dimensional (3D) plasmonic hot spots for label-free sensing and effective
      photothermal killing of multiple drug resistant superbugs.
AB  - Drug resistant superbug infection is one of the foremost threats to human health.
      Plasmonic nanoparticles can be used for ultrasensitive bio-imaging and
      photothermal killing by amplification of electromagnetic fields at nanoscale "hot
      spots". One of the main challenges to plasmonic imaging and photothermal killing
      is design of a plasmonic substrate with a large number of "hot spots". Driven by
      this need, this article reports design of a three-dimensional (3D) plasmonic "hot
      spot"-based substrate using gold nanoparticle attached hybrid graphene oxide
      (GO), free from the traditional 2D limitations. Experimental results show that
      the 3D substrate has capability for highly sensitive label-free sensing and
      generates high photothermal heat. Reported data using p-aminothiophenol
      conjugated 3D substrate show that the surface enhanced Raman spectroscopy (SERS)
      enhancement factor for the 3D "hot spot"-based substrate is more than two orders
      of magnitude greater than that for the two-dimensional (2D) substrate and five
      orders of magnitude greater than that for the zero-dimensional (0D) p
      aminothiophenol conjugated gold nanoparticle. 3D-Finite-Difference Time-Domain
      (3D-FDTD) simulation calculations indicate that the SERS enhancement factor can
      be greater than 104 because of the bent assembly structure in the 3D substrate.
      Results demonstrate that the 3D-substrate-based SERS can be used for fingerprint
      identification of several multi-drug resistant superbugs with detection limits of
      5 colony forming units per mL. Experimental data show that 785 nm near infrared
      (NIR) light generates around two times more photothermal heat for the 3D
      substrate with respect to the 2D substrate, and allows rapid and effective
      killing of 100% of the multi-drug resistant superbugs within 5 minutes.

PMID- 27714100
TI  - Ordered gyroidal tantalum oxide photocatalysts: eliminating diffusion limitations
      and tuning surface barriers.
AB  - In this work we synthesized well-ordered, Ta2O5 films with a 3D-interconnected
      gyroid mesopore architecture with large pore sizes beyond 30 nm and extended
      crystalline domains through self-assembly of tailor-made triblock-terpolymers.
      This has effectively eliminated diffusion limitations inherent to previously
      reported mesoporous photocatalysts and resulted in superior hydrogen evolution
      with apparent quantum yields of up to 4.6% in the absence of any cocatalyst. We
      further show that the injection barrier at the solid-liquid interface constitutes
      a key criterion for photocatalytic performance and can be modified by the choice
      of the carbon template. This work highlights pore and surface engineering as a
      promising tool towards high-performance mesoporous catalysts and electrodes for
      various energy-related applications.

PMID- 27714101
TI  - Fractal growth of platinum electrodeposits revealed by in situ electron
      microscopy.
AB  - Fractals are commonly observed in nature and elucidating the mechanisms of
      fractal-related growth is a compelling issue for both fundamental science and
      technology. Here we report an in situ electron microscopy study of dynamic
      fractal growth of platinum during electrodeposition in a miniaturized
      electrochemical cell at varying growth conditions. Highly dendritic growth -
      either dense branching or ramified islands - are formed at the solid-electrolyte
      interface. We show how the diffusion length of ions in the electrolyte influences
      morphology selection and how instability induced by initial surface roughness,
      combined with local enhancement of electric field, gives rise to non-uniform
      branched deposition as a result of nucleation/growth at preferred locations.
      Comparing the growth behavior under these different conditions provides new
      insight into the fundamental mechanisms of platinum nucleation.

PMID- 27714102
TI  - Ultrafast fabrication of highly active BiVO4 photoanodes by hybrid microwave
      annealing for unbiased solar water splitting.
AB  - Hybrid microwave annealing (HMA) with a silicon susceptor in a household
      microwave oven produces BiVO4-based photoanodes of much improved performance in
      photoelectrochemical water oxidation in only 6 min relative to conventional
      thermal annealing in a traditional muffle furnace (FA) that needs a much longer
      time, 300 min. This technique can apply equally effectively to bare as well as
      modified BiVO4 by Mo-doping, heterojunction formation with WO3, and an oxygen
      evolution co-catalyst. Relative to FA, HMA forms BiVO4 films of smaller feature
      sizes, higher porosity, and increased three dimensional roughness, which decrease
      the diffusion distance of holes to the surface and thereby increase mainly the
      bulk charge separation efficiency (etabulk) of the photoanodes. Thus, the HMA
      treated BiVO4/WO3 film achieves the state-of-the art etabulk of ~90% for water
      oxidation. Combination of a photoanode of NiOOH/FeOOH/BiVO4/WO3 (HMA, 6 min) with
      a 2p c-Si solar cell allows a solar to hydrogen conversion efficiency of ~5.0% in
      unbiased overall water splitting, which is also comparable to the state-of-the
      art for a similar material combination.

PMID- 27714103
TI  - Competition between self-inclusion and drug binding explains the pH dependence of
      the cyclodextrin drug carrier - molecular modelling and electrochemistry studies.
AB  - A non-toxic lipoic acid derivative of beta cyclodextrin (betaCDLip) with an
      electron-rich aromatic linker was studied as a carrier for the drug doxorubicin
      with the aim of decreasing the toxic side effects of this drug. The modified
      cyclodextrin strengthened the drug binding and differentiated the complex-forming
      ability with dependence on pH. The stability constants of the complexes were
      evaluated by voltammetry and spectrofluorometry. Molecular modelling provided
      deeper insight into the nature of the ligand structure itself and the drug-ligand
      interactions, showing the different contributions of the self-inclusion of the
      ligand substituent at different pH values. As a result, the modes of interaction
      of betaCDLip with the drug and factors affecting the stabilities of the complex
      under the pH conditions of healthy and tumour cells could be discovered and
      explained.

PMID- 27714104
TI  - A 3D co-culture microtissue model of the human placenta for nanotoxicity
      assessment.
AB  - There is increasing evidence that certain nanoparticles (NPs) can overcome the
      placental barrier, raising concerns on potential adverse effects on the growing
      fetus. But even in the absence of placental transfer, NPs may pose a risk to
      proper fetal development if they interfere with the viability and functionality
      of the placental tissue. The effects of NPs on the human placenta are not well
      studied or understood, and predictive in vitro placenta models to achieve
      mechanistic insights on NP-placenta interactions are essentially lacking. Using
      the scaffold-free hanging drop technology, we developed a well-organized and
      highly reproducible 3D co-culture microtissue (MT) model consisting of a core of
      placental fibroblasts surrounded by a trophoblast cell layer, which resembles the
      structure of the in vivo placental tissue. We could show that secretion levels of
      human chorionic gonadotropin (hCG) were significantly higher in 3D than in 2D
      cell cultures, which indicates an enhanced differentiation of trophoblasts grown
      on 3D MTs. NP toxicity assessment revealed that cadmium telluride (CdTe) and
      copper oxide (CuO) NPs but not titanium dioxide (TiO2) NPs decreased MT viability
      and reduced the release of hCG. NP acute toxicity was significantly reduced in 3D
      co-culture MTs compared to 2D monocultures. Taken together, 3D placental MTs
      provide a new and promising model for the fast generation of tissue-relevant
      acute NP toxicity data, which are indispensable for the safe development of NPs
      for industrial, commercial and medical applications.

PMID- 27714105
TI  - Mechanism of potassium ion intercalation staging in few layered graphene from in
      situ Raman spectroscopy.
AB  - Recently emerging potassium ion (K-ion) batteries offer a lower-cost alternative
      to lithium-ion batteries while enabling comparably high storage capacity. Here,
      we leverage the strong Raman spectroscopic response of few-layered graphene to
      provide the first insight into the electrochemical staging sequence for K+ ions
      in graphitic carbons. Our analysis reveals the signature of a dilute stage I
      compound that precedes formation of ordered intercalation compounds transitioning
      from stage VI (KC72), stage II (KC24), and stage I (KC8) and correlates
      electrochemical responses to the stage formation. Overall, our study emphasizes a
      minimum barrier to transfer the general understanding acquired for lithium-ion
      battery anodes to cheaper, earth abundant K-ion battery systems ideally suited
      for grid-scale storage.

PMID- 27714106
TI  - The influence of interfacial tensile strain on the charge transport
      characteristics of MoS2-based vertical heterojunction devices.
AB  - We demonstrate the charge transport characteristics of MoS2-based vertical
      heterojunction devices through the formation of interfacial strain. Atomically
      thin MoS2 bilayers were directly synthesized on a p-type Si substrate by using
      chemical vapor deposition to introduce an interfacial tensile strain in the
      vertical heterojunction diode structure, which was confirmed by Raman, X-ray and
      ultraviolet photoelectron spectroscopy techniques. The electrical and
      optoelectronic properties of the heterojunction devices with the as-grown MoS2 (A
      MoS2) on p-Si were compared with those of transferred MoS2 (T-MoS2)/p-Si devices.
      To clearly understand the charge transport characteristics induced by the
      interfacial tensile strain, the Fowler-Nordheim (FN) analysis of the electrical
      properties of the diode devices was conducted with the corresponding energy band
      diagrams. All of the fabricated MoS2-based vertical diodes exhibited clearly
      rectifying behaviors, but the photoresponse properties of the A-MoS2-based and T
      MoS2-based heterojunctions exhibited distinct differences. Interestingly, we
      found that the tunneling barrier heights of the A-MoS2-based heterojunction
      devices were relatively higher than those of the T-MoS2-based devices and were
      almost the same before and after illumination due to the interfacial tensile
      strain, whereas those of the T-MoS2-based devices were lowered after
      illumination. Our study will help further understand the charge transport
      properties of 2D material-based heterojunction devices in the presence of
      interfacial strain, ultimately enabling the design of electronic and
      optoelectronic devices with novel functionalities.

PMID- 27714107
TI  - Combining surface plasmonic and light extraction enhancement on InGaN quantum
      well light-emitters.
AB  - Surface plasmon coupling with light-emitters and surface nano-patterning have
      widely been used separately to improve low efficiency InGaN light-emitting
      diodes. We demonstrate a method where dielectric nano-patterning and Ag
      nanoparticles (NPs) are combined to provide both light extraction and internal
      quantum efficiency enhancement for InGaN/GaN quantum-well light-emitters. By
      fabricating dielectric nano-rod pattern on the GaN surface, an optical coating
      that improves the light extraction is obtained, and furthermore has a low
      refractive index which blue-shifts the plasmonic resonance of Ag NPs towards the
      emission wavelength. We investigate emission components from both the GaN and
      sapphire surface of the semiconductor crystal and show that Ag NPs on dielectric
      nano-pattern compared to a planar surface, result in a stronger enhancement.

PMID- 27714108
TI  - Carbohydrate-based amphiphilic nano delivery systems for cancer therapy.
AB  - Nanoparticles (NPs) are novel drug delivery systems that have been attracting
      more and more attention in recent years, and have been used for the treatment of
      cancer, infection, inflammation and other diseases. Among the numerous classes of
      materials employed for constructing NPs, organic polymers are outstanding due to
      the flexibility of design and synthesis and the ease of modification and
      functionalization. In particular, NP based amphiphilic polymers make a great
      contribution to the delivery of poorly-water soluble drugs. For example, natural,
      biocompatible and biodegradable products like polysaccharides are widely used as
      building blocks for the preparation of such drug delivery vehicles. This review
      will detail carbohydrate based amphiphilic polymeric systems for cancer therapy.
      Specifically, it focuses on the nature of the polymer employed for the
      preparation of targeted nanocarriers, the synthetic methods, as well as
      strategies for the application and evaluation of biological activity.
      Applications of the amphiphilic polymer systems include drug delivery, gene
      delivery, photosensitizer delivery, diagnostic imaging and specific ligand
      assisted cellular uptake. As a result, a thorough understanding of the
      relationship between chemical structure and biological properties facilitate the
      optimal design and rational clinical application of the resulting carbohydrate
      based nano delivery systems for cancer therapy.

PMID- 27714109
TI  - Transparent multi-layer graphene/polyethylene terephthalate structures with
      excellent microwave absorption and electromagnetic interference shielding
      performance.
AB  - A high-performance electromagnetic interference (EMI) shielding structure based
      on pure graphene (without doping) consists of several graphene sheets separated
      by transparent polyethylene terephthalate (PET) films. We report the theoretical
      and experimental design, and characterization of the multi-layer graphene/PET
      structures. With a total graphene thickness of only 4 nm, the graphene/PET sample
      demonstrated an average shielding effectiveness of 19.14 dB at 18-26.5 GHz, with
      a maximum microwave absorbance of 95.82% at 25.7 GHz, while maintaining a
      normalized visible transmittance of 80.5%. For the multi-layer graphene/PET
      samples, the contribution of absorption to the total shielding exceeds 96%,
      indicating that absorption is the dominant shielding mechanism, instead of
      reflection. The microwave absorbance of the multi-layer graphene/PET structure
      increases rapidly from the mono- to the four-layer structures, and then more
      gradually as the number of layers continues to increase when the thickness of PET
      is 1 mm. In addition, the microwave absorbance can be improved two-fold by
      increasing the separation between graphene layers. We believe that this multi
      layer graphene/PET structure, which exhibits high-performance microwave
      absorption and shielding, has great potential for applications in transparent EMI
      shielding devices, especially if EMI absorption is required.

PMID- 27714110
TI  - Mechanism of photocatalytic activity improvement of AgNPs/TiO2 by oxygen plasma
      irradiation.
AB  - Plasmonic metal Ag nanoparticles (AgNPs) on TiO2 thin films (AgNPs/TiO2) are a
      kind of excellent photocatalyst of high efficiency under visible light, and thus
      draw great interest nowadays. Further improvement of their photocatalytic
      activity (PA) is difficult but is of high importance for their applications. In
      this paper, oxygen plasma was taken to partially oxidize AgNPs deposited on the
      surface of TiO2 to form a structure with the configuration of a p-type
      semiconductor/plasmonic metal/n-type semiconductor (Ag2O/AgNPs/TiO2). The
      localized surface plasmon resonance (LSPR) of the AgNPs was strongly damped after
      oxygen plasma irradiation (OPI) but the photocatalytic activity was improved. The
      mechanisms of the photocatalytic activity improvement under UV and visible light
      were explored based on charge kinetics.

PMID- 27714111
TI  - Transferrin conjugated nontoxic carbon dots for doxorubicin delivery to target
      pediatric brain tumor cells.
AB  - Among various cancers, pediatric brain tumors represent the most common cancer
      type in children and the second most common cause of cancer related deaths.
      Anticancer drugs and therapies, such as doxorubicin (Dox), have severe side
      effects on patients during chemotherapy, especially for children as their bodies
      are still under development. These side effects are believed to be due to the
      lack of a delivery system with high efficacy and targeting selectivity, resulting
      in serious damages of normal cells. To improve the efficacy and selectivity, the
      transferrin (Trans) receptor mediated endocytosis can be utilized for drug
      delivery system design, as transferrin receptors are expressed on the blood brain
      barrier (BBB) and often over expressed in brain tumor cells. Carbon dots (C-Dots)
      have recently emerged as benign nanoparticles in biomedical applications owing to
      their good water solubility, tunable surface functionalities and excellent
      biocompatibility. The unique characteristics of C-Dots make them promising
      candidates for drug delivery development. In this study, carbon dots-transferrin
      doxorubicin covalent conjugate (C-Dots-Trans-Dox) was synthesized, characterized
      by different spectroscopic techniques and investigated for the potential
      application as a drug delivery system for anticancer drug doxorubicin to treat
      pediatric brain tumors. Our in vitro results demonstrate greater uptake of the C
      Dots-Trans-Dox conjugate compared to Dox alone presumably owing to the high
      levels of transferrin receptors on these tumor cells. Experiment showed that C
      Dots-Trans-Dox at 10 nM was significantly more cytotoxic than Dox alone, reducing
      viability by 14-45%, across multiple pediatric brain tumor cell lines.

PMID- 27714112
TI  - Modulating the optical properties of the AIE fluophor confined within UiO-66's
      nanochannels for chemical sensing.
AB  - Transformation of aggregation induced emission (AIE) molecules into functional
      materials can greatly tune their fluorescence properties and expand their related
      potential applications. Here, we demonstrate a facile strategy to modulate the
      fluorescence properties of AIE molecules by confining them within the
      nanochannels of metal-organic frameworks (MOFs). AIE molecules (4,4'-(hydrazine
      1,2-diylidene bis(methanylylidene)) bis(3-hydroxybenzoic acid), HDBB) with pH
      dependent emission were successfully integrated into UiO-66 resulting in a UiO
      66?HDBB complex while maintaining the crystal structure by the host-guest
      process. The fluorescence properties of HDBB can be modulated by virtue of the
      unique nanospace confining effect. Furthermore, UiO-66?HDBB was used as a
      sensitive and selective fluorescent probe for Cu2+ detection in aqueous solution.
      This study provides a facile strategy for the construction of high performance
      AIE based luminescent materials with adjustable properties for potential
      applications.

PMID- 27714113
TI  - Thermal conductivity of disordered two-dimensional binary alloys.
AB  - Using non-equilibrium molecular dynamics simulations, we have studied the effect
      of disorder on the thermal conductivity of two-dimensional (2D) C1-xNx alloys. We
      find that the thermal conductivity not only depends on the substitution
      concentration of nitrogen, but also strongly depends on the disorder
      distribution. A general linear relationship is revealed between the thermal
      conductivity and the participation ratio of phonons in 2D alloys. Localization
      mode analysis further indicates that the thermal conductivity variation in the
      ordered alloys can be attributed to the number of inequivalent atoms. As for the
      disordered alloys, we find that the thermal conductivity variation can be
      described by a simple linear formula with the disorder degree and the
      substitution concentration. The present study suggests some general guidance for
      phonon manipulation and thermal engineering in low dimensional alloys.

PMID- 27714114
TI  - Highly controllable double Fano resonances in plasmonic metasurfaces.
AB  - Creating plasmonic nanostructures with controllable Fano resonances is of great
      interest for a number of important applications including metamaterials and
      biosensors. Realizing double Fano resonances is even more challenging but may
      become favorable to the applications such as surface enhanced Raman scattering
      (SERS) and second harmonic generation (SHG). Here we have developed plasmonic
      metasurfaces consisting of a nanoring array and a metallic film separated by a
      dielectric spacer for the generation of double Fano resonances. The double Fano
      resonances are realized by the strong plasmonic coupling between the localized
      surface plasmon resonance (LSPR) mode of the nanoring array and the cavity modes
      of the metal-insulator-metal (MIM) structure, and consequently exhibit large
      electric field enhancements at double frequencies. The resonance wavelength, the
      linewidth and the wavelength separation of double Fano resonances can be well
      tailored by changing the cavity length of the structure and the parameters of the
      top array pattern including the diameter, periodicity, and shape. In addition, we
      develop a far-field coupling model to efficiently determine the cavity length of
      metasurface structures with double Fano resonances at specific wavelengths with
      much ease and acceptable accuracy compared to the time-consuming and computing
      resource-needed numerical simulations.

PMID- 27714115
TI  - Size-tunable synthesis of monolayer MoS2 nanoparticles and their applications in
      non-volatile memory devices.
AB  - We report the CVD synthesis of a monolayer of MoS2 nanoparticles such that the
      nanoparticle size was controlled over the range 5-100 nm and the chemical
      potential of sulfur was modified, both by controlling the hydrogen flow rate
      during the CVD process. As the hydrogen flow rate was increased, the reaction
      process of sulfur changed from a "sulfiding" process to a "sulfo-reductive"
      process, resulting in the growth of smaller MoS2 nanoparticles on the substrates.
      The size control, crystalline quality, chemical configuration, and distribution
      uniformity of the CVD-grown monolayer MoS2 nanoparticles were confirmed. The
      growth of the MoS2 nanoparticles at different edge states was studied using
      density functional theory calculations to clarify the size-tunable mechanism. A
      non-volatile memory device fabricated using the CVD-grown size-controlled 5 nm
      monolayer MoS2 nanoparticles as a floating gate showed a good memory window of 5
      8 V and an excellent retention period of a decade.

PMID- 27714116
TI  - Long-term stability improvement of light-emitting diode using highly transparent
      graphene oxide paste.
AB  - A highly transparent paste adhesive is successfully fabricated by introducing
      graphene oxide (GO) to silicone paste adhesive by using a solvent-exchange
      method. The GO incorporated in the paste adhesive has a significant role in
      improving thermal conductivity, transparency and adhesive strength. The GO
      embedded silicone paste is applied as a die-attach paste to light-emitting diodes
      (LEDs) in order to enhance the optical quality of the LEDs. The presence of GO in
      the die-attach layer of the LEDs gives rise to the enhancement of luminous
      intensity, effective heat dissipation, improvement of moisture barrier property
      as well as high adhesive strength. Consequently, the LEDs with the GO-embedded
      die-attach paste exhibit enhanced long-term stability. This novel approach
      provides a feasible and effective strategy for improving LED performance.

PMID- 27714117
TI  - A mesoporous organosilica nano-bowl with high DNA loading capacity - a potential
      gene delivery carrier.
AB  - Mesoporous organosilica nanoparticles with a novel bowl-like morphology were
      synthesized. These nano-bowls possess uniform particle sizes around 180 nm and
      open cavities around 140 nm, which lead to higher loading capability for plasmid
      DNA than traditional silica-based nanoparticles. In vitro DNA transfection using
      these nano-bowls is demonstrated.

PMID- 27714118
TI  - A strategy to improve the efficiency of hole transporting materials: introduction
      of a highly symmetrical core.
AB  - The electronic, optical and hole transport properties of three new hole
      transporting materials (HTMs) with a planar core have been investigated by using
      density functional theory and Marcus theory. A reliable semi-rational formula was
      adopted to calculate the highest occupied molecular orbital (HOMO) levels of new
      HTMs. The results showed that the HOMO levels of new HTMs were 0.07-0.30 eV lower
      than those of Spiro-OMeTAD, and their absorption peaks appeared outside or close
      to the visible region and overlapped slightly with the absorption band of
      perovskites. Moreover, the Stokes shifts of the designing molecules were
      calculated to lie in a range from 72 to 124 nm, meaning that they could undergo
      large geometrical changes on excitation. More importantly, the hole mobility of
      new HTMs (0.099-0.27 cm2 v-1 s-1) was approximately two orders of magnitude
      higher than that of Spiro-OMeTAD (0.0056 cm2 v-1 s-1) due to strong hole coupling
      from a face-to-face packing pattern. Our results indicated that planar core-based
      HTMs could become potential candidates to replace the widely established Spiro
      OMeTAD.

PMID- 27714119
TI  - Highly active, stable and self-antimicrobial enzyme catalysts prepared by
      biomimetic mineralization of copper hydroxysulfate.
AB  - A nature-inspired approach to encapsulate enzymes in spindle-like copper
      hydroxysulfate nanocrystals was developed by a biomimetic mineralization process.
      Several types of enzymes including glucose oxidase (GOx), horseradish peroxidase
      (HRP), Candida antarctica lipase B (CALB) and cytochrome c (Cyt c) were
      successfully encapsulated in copper hydroxysulfate nanocrystals quickly (within 1
      hour) with maintained or even greatly enhanced catalytic efficiencies (kcat/KM of
      Cyt c showed a 143-fold increase) and high stabilities, demonstrating the
      feasibility of utilizing copper hydroxysulfate nanocrystals as a novel type of
      nanocarrier for enzyme immobilization. In addition, by this approach, for the
      first time, we showed that an immobilized enzyme can be endowed with self
      antibacterial activity by an inorganic component. This self-antibacterial
      performance together with the improved catalytic efficiencies and stabilities can
      greatly benefit the enzymatic catalysis in aqueous media and promote the future
      development of novel biosensors.

PMID- 27714120
TI  - Tuning of the photoluminescence and up-conversion photoluminescence properties of
      single-walled carbon nanotubes by chemical functionalization.
AB  - Single-walled carbon nanotubes (SWNTs) were subjected to alkylation using alkyl
      bromide and alkyl dibromide, and the photoluminescence (PL) properties of the
      resulting alkylated SWNTs were characterized. Two new PL peaks were observed
      along with the intrinsic PL peak at 976 nm when alkyl bromide was used (SWNT-Bu:
      ~1095 and 1230 nm, SWNT-Bn: 1104 and 1197 nm). In contrast, the use of
      alpha,alpha'-dibromo-o-xylene as an alkyl dibromide primarily resulted in only
      one new PL peak, which was observed at 1231 nm. The results revealed that the
      Stokes shift of the new peaks was strongly influenced by the addition patterns of
      the substituents. In addition, the time-resolved PL decay profiles of the
      alkylated SWNTs revealed that the PL peaks possessing a larger Stokes shift had
      longer exciton lifetimes. The up-conversion PL (UCPL) intensity of the alkylated
      SWNTs at excitation wavelengths of 1100 and 1250 nm was estimated to be ~2.38 and
      ~2.35 times higher than that of the as-dispersed SWNTs, respectively.

PMID- 27714121
TI  - The dissipation of field emitting carbon nanotubes in an oxygen environment as
      revealed by in situ transmission electron microscopy.
AB  - In this work, we report the first direct experimental observations of carbon
      nanotubes (CNT) field emitting in an oxygen environment, using aberration
      corrected environmental transmission electron microscopy in combination with an
      electrical biasing specimen holder under low-dose, field-free imaging conditions.
      Our studies show that while the CNTs remain stable during high vacuum field
      emission, they experience abrupt decreases in length, also termed "burn-back",
      when field-emitting in an oxygen environment at around 30 Pa pressure.
      Furthermore, we perform correlative field-free and aberration-corrected, high
      resolution transmission electron microscopy imaging to understand how the
      structure of the CNTs - particularly the opening of the nanotube caps - is
      influenced by its gas environment during field emission. This work provides
      significant insight into the mechanism of carbon nanotube behavior under non
      ideal field emission conditions.

PMID- 27714122
TI  - Optofluidic sensing from inkjet-printed droplets: the enormous enhancement by
      evaporation-induced spontaneous flow on photonic crystal biosilica.
AB  - Novel transducers for detecting an ultra-small volume of an analyte solution play
      pivotal roles in many applications such as chemical analysis, environmental
      protection and biomedical diagnosis. Recent advances in optofluidics offer
      tremendous opportunities for analyzing miniature amounts of samples with high
      detection sensitivity. In this work, we demonstrate enormous enhancement factors
      (106-107) of the detection limit for optofluidic analysis from inkjet-printed
      droplets by evaporation-induced spontaneous flow on photonic crystal biosilica
      when compared with conventional surface-enhanced Raman scattering (SERS) sensing
      using the pipette dispensing technology. Our computational fluid dynamics
      simulation has shown a strong recirculation flow inside the 100 picoliter droplet
      during the evaporation process due to the thermal Marangoni effect. The
      combination of the evaporation-induced spontaneous flow in micron-sized droplets
      and the highly hydrophilic photonic crystal biosilica is capable of providing a
      strong convection flow to combat the reverse diffusion force, resulting in a
      higher concentration of the analyte molecules at the diatom surface. In the
      meanwhile, high density hot-spots provided by the strongly coupled plasmonic
      nanoparticles with photonic crystal biosilica under a 1.5 MUm laser spot are
      verified by finite-difference time domain simulation, which is crucial for SERS
      sensing. Using a drop-on-demand inkjet device to dispense multiple 100 picoliter
      analyte droplets with pinpoint accuracy, we achieved the single molecule
      detection of Rhodamine 6G and label-free sensing of 4.5 * 10-17 g trinitrotoluene
      from only 200 nanoliter solution.

PMID- 27714123
TI  - Controllable synthesis of ultra-small metal-organic framework nanocrystals
      composed of copper(ii) carboxylates.
AB  - Controlling the size of metal-organic frameworks (MOFs) down to the nanoscale is
      of great importance for the optimization of their properties. Chemically
      synthesized MOF nanoparticles commonly range from tens of nanometers to several
      microns. Herein, a general two-ligand modulation strategy in an interface
      reaction system is developed to synthesize a series of ultra-small MOF
      nanocrystals composed of copper(ii) ions and carboxylate linkers. The size of
      these MOF nanocrystals can be tuned within 10 nm by the alkyl chain length, the
      ligand to metal ion ratio and the reaction time. The ion exchange and self
      assembly of the MOF nanocrystals were also investigated. They are well dispersed
      in nonpolar solvents applicable for spin-coating, suggesting their application
      potentials in functional thin film devices.

PMID- 27714124
TI  - Distinct metal-exchange pathways of doped Ag25 nanoclusters.
AB  - Atomically precise metal nanoclusters (NCs) containing more than one type of
      metal atom (i.e., doped or alloyed), due to synergistic effects, open new avenues
      for engineering the catalytic and optical properties of NCs in a manner that
      homometal NCs cannot. Unfortunately, it is still a major challenge to
      controllably introduce multimetallic dopants in NCs, understanding the dopants'
      positions, mechanism, and synergistic effects. To overcome these challenges, we
      designed a metal-exchange approach involving NCs as molecular templates and metal
      ions as the source of the incoming dopant. In particular, two structurally
      similar monodoped silver-rich NCs, [MAg24(SR)18]2- (M = Pd/Pt and SR: thiolate),
      were synthesized as templates to study their mechanistic transformation in
      response to the introduction of gold atoms. The controllable incorporation of Au
      atoms into the MAg24 framework facilitated the elucidation of distinct doping
      pathways through high-resolution mass spectrometry, optical spectroscopy and
      elemental analysis. Interestingly, gold replaced the central Pd atom of
      [PdAg24(SR)18]2- clusters to produce predominantly bimetallic [AuAg24(SR)18]-
      clusters along with a minor product of an [Au2Ag23(SR)18]- cluster. In contrast,
      the central Pt atom remained intact in [PtAg24(SR)18]2- clusters, and gold
      replaced the non-central Ag atoms to form trimetallic [AuxPtAg24-x(SR)18]2- NCs,
      where x = 1-2, with a portion of the starting [PtAg24(SR)18]2- NCs remaining.
      This study reveals some of the unusual metal-exchange pathways of doped NCs and
      the important role played by the initial metal dopant in directing the position
      of a second dopant in the final product.

PMID- 27714125
TI  - Turning off the majority-rules effect in two-dimensional hierarchical chiral
      assembly by introducing a chiral mismatch.
AB  - Understanding the mechanism in chiral transmission from a single molecule to a
      supramolecular level is fundamentally important to decipher the nonlinear
      amplification effect in the two-dimensional (2D) chiral assembly process. In this
      contribution, we report on the dramatically different nonlinear amplification
      effect in the chiral co-adsorber induced homochiral assemblies constructed by a
      series of homologous achiral building blocks on the graphite surface under
      control of the majority-rules principle. Homologous hexagonal networks are formed
      for 5-(benzyloxy)-isophthalic acid (BIC) derivatives with different alkyl
      lengths. While globally homochiral monolayers of BIC-C6 or BIC-C16 can be
      obtained by using a mixture of chiral co-adsorber 2-octanol with a small
      enantiomeric excess, such majority-rules principle based nonlinear chiral
      amplification is inoperative for the assembly of BIC-C10. Molecular mechanistic
      analysis indicates that BIC-C10 assembly can accommodate a chiral mismatched
      motif to form long-range ordered but short-range disordered crystalline networks,
      leading to the co-adsorption of enantiomers without enantioselectivity. The
      present results shed important insights into the significance of chirality
      mismatch during chiral transmission and benefit the understanding of chiral
      communication in a surface monolayer.

PMID- 27714126
TI  - 2D/3D perovskite hybrids as moisture-tolerant and efficient light absorbers for
      solar cells.
AB  - The lifetime and power conversion efficiency are the key issues for the
      commercialization of perovskite solar cells (PSCs). In this paper, the
      development of 2D/3D perovskite hybrids (CA2PbI4/MAPbIxCl3-x) was firstly
      demonstrated to be a reliable method to combine their advantages, and provided a
      new concept for achieving both stable and efficient PSCs through the
      hybridization of perovskites. 2D/3D perovskite hybrids afforded significantly
      improved moisture stability of films and devices without encapsulation in a high
      humidity of 63 +/- 5%, as compared with the 3D perovskite (MAPbIxCl3-x). The
      2D/3D perovskite-hybrid film did not undergo any degradation after 40 days, while
      the 3D perovskite decomposed completely under the same conditions after 8 days.
      The 2D/3D perovskite-hybrid device maintained 54% of the original efficiency
      after 220 hours, whereas the 3D perovskite device lost all the efficiency within
      only 50 hours. Moreover, the 2D/3D perovskite hybrid achieved comparable device
      performances (PCE: 13.86%) to the 3D perovskite (PCE: 13.12%) after the
      optimization of device fabrication conditions.

PMID- 27714127
TI  - Programmable RNA microstructures for coordinated delivery of siRNAs.
AB  - RNA is a natural multifunctional polymer, and is an essential component in both
      complex pathways and structures within the cellular environment. For this reason,
      artificial self-assembling RNA nanostructures are emerging as a powerful tool
      with broad applications in drug delivery and metabolic pathway regulation. To
      date, coordinated delivery of functional molecules via programmable RNA
      assemblies has been primarily done using nanosize RNA scaffolds. However, larger
      scaffolds could expand existing capabilities for spatial arrangement of ligands,
      and enable the controlled delivery of highly concentrated molecular loads. Here,
      we investigate whether micron-size RNA scaffolds can be assembled and further
      functionalized with different cargos (e.g. various siRNAs and fluorescent tags)
      for their synchronized delivery to diseased cells. Since known design approaches
      to build large RNA scaffolds are still underdeveloped, we apply a tiling method
      widely used in DNA nanotechnology. DNA tiles have been extensively used to build
      a variety of scalable and modular structures that are easily decorated with other
      ligands. Here, we adapt a double crossover (DX) DNA tile motif to design de novo
      DX RNA tiles that assemble and form lattices via programmed sticky end
      interactions. We optimize assembly protocols to guarantee high yield of RNA
      lattices. The resulting constructs are robust and modular with respect to the
      presence of distinct siRNAs and fluorophores. RNA tiles and lattices are
      successfully transfected in either human breast cancer or prostate cancer cells,
      where they efficiently knockdown the expression of target genes. Blood serum
      stability assays indicate that RNA lattices are more resilient to nuclease
      degradation when compared to individual tiles, thus making them better suited for
      therapeutic purposes. Overall, because of its design simplicity, we anticipate
      that this approach will be utilized for a wide range of applications in
      therapeutic RNA nanotechnology.

PMID- 27714128
TI  - Role of shape in substrate-induced plasmonic shift and mode uncovering on gold
      nanocrystals.
AB  - A number of plasmonic devices and applications, such as chemical and biological
      sensors, plasmon-enhanced solar cells, optical nanoantennas, metamaterials and
      metasurfaces, require the deposition of plasmonic metal nanocrystals on various
      substrates. Because the localized plasmon resonance modes, energies and strengths
      are strongly dependent on the dielectric function of the surrounding environment,
      the substrate is expected to largely affect the plasmonic properties of supported
      metal nanocrystals. Therefore, understanding the effects of the substrate on the
      plasmonic properties of metal nanocrystals and the roles of the involved factors
      will be crucial for designing various plasmonic devices that are made of metal
      nanocrystals deposited on different substrates. Herein we report on our study and
      results of the effects of substrates with distinct dielectric functions on the
      plasmonic properties of three types of Au nanocrystals. A combination of
      experiments and numerical simulations shows that the presence of a substrate
      causes plasmonic shifts as well as the appearance of new plasmon modes. The
      plasmonic shifts and the emergence of new plasmon modes are found to be dependent
      on the particle shape of Au nanocrystals and in turn on the fractional particle
      surface area that is in contact with the supporting substrate. For Au nanospheres
      and nanorods, plasmonic shifts, less than 100 nm, are observed on the scattering
      spectra by changing the supporting substrate from indium tin oxide to silicon. In
      comparison, a giant spectral shift of more than 300 nm is obtained for Au
      nanoplates. Moreover, silicon substrates induce the emergence of an out-of-plane
      quadrupolar mode of Au nanoplates, which interacts with an out-of-plane octupolar
      mode to give rise to a distinct Fano resonance. The Fano resonance is found to
      become stronger as the thickness of Au nanoplates is decreased. These results are
      of great importance for understanding the plasmonic properties of noble metal
      nanocrystals supported on various substrates, and for designing novel plasmonic
      nanostructures with desired optical properties and functions.

PMID- 27714129
TI  - Geometric structure, electronic structure and optical absorption properties of
      one-dimensional thiolate-protected gold clusters containing a quasi-face-centered
      cubic (quasi-fcc) Au-core: a density-functional theoretical study.
AB  - Based on the recently reported atomic structures of thiolate-protected
      Au28(SR)20, Au36(SR)24, Au44(SR)28, and Au52(SR)32 clusters, a family of
      homogeneous, linear, thiolate-protected gold superstructures containing novel
      quasi-face-centered-cubic (quasi-fcc) Au-cores is theoretically envisioned,
      denoted as the Au20+8N(SR)16+4N cluster. By means of density functional theory
      (DFT) and time-dependent DFT (TD-DFT) calculations, a unified view of the
      geometric structure, electronic structure, magic stable size and size-dependent
      NIR absorption properties of Au20+8N(SR)16+4N clusters is provided. We find that
      the Au20+8N(SR)16+4N clusters demonstrate oscillating transformation energies
      dependent on N. The odd-N clusters show more favorable (negative) reaction
      energies than the even-N clusters. The magic stability of recently reported
      Au28(SR)20, Au36(SR)24, Au44(SR)28, Au52(SR)32 and Au76(SR)44 clusters can be
      addressed from the relative reaction energies and geometric distortion of Au
      cores. A novel 4N + 4 magic electron-number is suggested for the Au20+8N(SR)16+4N
      cluster. Using the polyhedral skeletal electron pair theory (PSEPT) and the
      extended Huckel molecular orbital (EHMO) calculations, we suggest that the magic
      4N + 4 electron number is correlated with the quasi-fcc Au-cores, which can be
      viewed as double helical tetrahedron-Au4 chains. The size-dependent optical
      absorption properties of Au20+8N(SR)16+4N clusters are revealed based on TD-DFT
      calculations. We propose that these clusters are potential candidates for the
      experimental synthesis of atomically precise one-dimensional ligand protected
      gold superstructures with tunable NIR absorption properties.

PMID- 27714130
TI  - Covalently linked multimers of gold nanoclusters Au102(p-MBA)44 and Au~250(p
      MBA)n.
AB  - We present the synthesis, separation, and characterization of covalently-bound
      multimers of para-mercaptobenzoic acid (p-MBA) protected gold nanoclusters. The
      multimers were synthesized by performing a ligand-exchange reaction of a pre
      characterized Au102(p-MBA)44 nanocluster with biphenyl-4,4'-dithiol (BPDT). The
      reaction products were separated using gel electrophoresis yielding several
      distinct bands. The bands were analyzed by transmission electron microscopy (TEM)
      revealing monomer, dimer, and trimer fractions of the nanocluster. TEM analysis
      of dimers in combination with molecular dynamics simulations suggest that the
      nanoclusters are covalently bound via a disulfide bridge between BPDT molecules.
      The linking chemistry is not specific to Au102(p-MBA)44. The same approach yields
      multimers also for a larger monodisperse p-MBA-protected cluster of approximately
      250 gold atoms, Au~250(p-MBA)n. While the Au102(p-MBA)44 is not plasmonic, the
      Au~250(p-MBA)n nanocluster supports localized surface plasmon resonance (LSPR) at
      530 nm. Multimers of the Au~250(p-MBA)n exhibit additional transitions in their
      UV-vis spectrum at 630 nm and 810 nm, indicating the presence of hybridized LSPR
      modes. Well-defined structures and relatively small sizes make these systems
      excellent candidates for connecting ab initio theoretical studies and
      experimental quantum plasmonics. Moreover, our work opens new possibilities in
      the controlled synthesis of advanced monodisperse nanocluster superstructures.

PMID- 27714131
TI  - C60(OH)22: a potential histone deacetylase inhibitor with anti-angiogenic
      activity.
AB  - C60(OH)22 has been reported to suppress human cancer by inhibiting angiogenesis.
      However, its mechanism of action remains unclear. To explore the role and
      mechanism of C60(OH)22 in human pancreatic cancer, siRNA knockdown,
      immunofluorescence and a matrigel plug mouse model were employed. The results
      demonstrated that C60(OH)22 suppresses endothelial cell invasion and tube
      formation in vitro. C60(OH)22 suppresses angiogenesis in human umbilical vein
      endothelial cell (HUVEC) xenograft mice. The enzymatic activities of MMP2 and
      MMP9, as well as the expression levels of HDAC1, HDAC2, HIF-1alpha and VEGF, were
      inhibited by C60(OH)22. The expression of RECK was up-regulated by C60(OH)22 in
      HUVECs. The expression levels of HIF-1alpha and VEGF were down-regulated and the
      expression of RECK was up-regulated after the knockdown of HDAC1 and HDAC2 in
      HUVECs. Cell invasion, tube formation, and the enzymatic activities of MMP2 and
      MMP9 were suppressed after the knockdown of HDAC1 or HDAC2 in HUVECs.

PMID- 27714132
TI  - Enzyme-free colorimetric determination of EV71 virus using a 3D-MnO2-PEG
      nanoflower and 4-MBA-MA-AgNPs.
AB  - We present a simple colorimetric assay for EV71 virus detection based on the
      aggregation of 4-mercaptobenzoic acid (4-MBA) and melamine (MA) modified silver
      nanoparticles (4-MBA-MA-AgNPs) in the presence of Mn2+. The EV71-Ab1 was
      incubated on a 96-well plate and the EV71-Ab2 was labeled on the surface of three
      dimensional nanoflower-like MnO2-PEG (3D-MnO2-PEG). After layer-by-layer
      immunoreactions, the EV71 virus and the corresponding 3D-MnO2-PEG-Ab2 were
      captured on the plate. With the addition of Vitamin C (Vc), Mn2+ was released
      from the 3D-MnO2-PEG and then the aggregation of the 4-MBA-MA-AgNPs was induced,
      allowing a naked-eye detection limit of EV71 virus to be as low as 5 * 104
      particles per mL, which is about three orders of magnitude lower than the
      conventional enzyme-linked immunosorbent assay (ELISA). This enzyme-free
      immunoassay based on a hybrid 3D-MnO2 features signal amplification strategies
      via a simple reduction reaction.

PMID- 27714133
TI  - Efficient vacuum-free-processed quantum dot light-emitting diodes with printable
      liquid metal cathodes.
AB  - Colloidal quantum dot light-emitting diodes (QLEDs) are recognized as promising
      candidates for next generation displays. QLEDs can be fabricated by low-cost
      solution processing except for the metal electrodes, which, in general, are
      deposited by costly vacuum evaporation. To be fully compatible with the low-cost
      solution process, we herein demonstrate vacuum-free and solvent-free fabrication
      of electrodes using a printable liquid metal. With eutectic gallium-indium
      (EGaIn) based liquid metal cathodes, vacuum-free-processed QLEDs are demonstrated
      with superior external quantum efficiencies of 11.51%, 12.85% and 5.03% for red,
      green and blue devices, respectively, which are about 2-, 1.5- and 1.1-fold
      higher than those of the devices with thermally evaporated Al cathodes. The
      improved performance is attributable to the reduction of electron injection by
      the native oxide of EGaIn, which serves as an electron-blocking layer for the
      devices and thus improves the balance of carrier injection. Also, the T50 half
      lifetime of the vacuum-free-processed QLEDs is about 2-fold longer than that of
      the devices with Al cathodes. Our results demonstrate that EGaIn-based solvent
      free liquid metals are promising printable electrodes for realizing efficient,
      low-cost and vacuum-free-processed QLEDs. The elimination of vacuum and high
      temperature processes significantly reduces the production cost and paves the way
      for industrial roll-to-roll manufacturing of large area displays.

PMID- 27714134
TI  - Superhalogens as building blocks of two-dimensional organic-inorganic hybrid
      perovskites for optoelectronics applications.
AB  - Organic-inorganic hybrid perovskites, well known for their potential as the next
      generation solar cells, have found another niche application in optoelectronics.
      This was demonstrated in a recent experiment (L. Dou, et al., Science, 2015, 349,
      1518) on atomically thin (C4H9NH3)2PbBr4, where, due to quantum confinement, the
      bandgap and the exciton binding energy are enhanced over their corresponding
      values in the three-dimensional bulk phase. Using density functional theory we
      show that when halogen atoms (e.g. I) are sequentially replaced with superhalogen
      molecules (e.g. BH4) the bandgap and exciton binding energy increase
      monotonically with the superhalogen content with the exciton binding energy of
      (C4H9NH3)2Pb(BH4)4 approaching the value in monolayer black phosphorus. Lead-free
      admixtures (C4H9NH3)2MI4-x(BH4)x (M = Sn and Ge; x = 0-4) also show a similar
      trend. Thus, a combination of quantum confinement and compositional change can be
      used as an effective strategy to tailor the bandgap and the exciton binding
      energy of two-dimensional hybrid perovskites, making them promising candidates
      for optoelectronic applications.

PMID- 27714135
TI  - Folate-based single cell screening using surface enhanced Raman microimaging.
AB  - Recent progress in nanotechnology and its application to biomedical settings have
      generated great advantages in dealing with early cancer diagnosis. The
      identification of the specific properties of cancer cells, such as the expression
      of particular plasma membrane molecular receptors, has become crucial in
      revealing the presence and in assessing the stage of development of the disease.
      Here we report a single cell screening approach based on Surface Enhanced Raman
      Scattering (SERS) microimaging. We fabricated a SERS-labelled nanovector based on
      the biofunctionalization of gold nanoparticles with folic acid. After treating
      the cells with the nanovector, we were able to distinguish three different cell
      populations from different cell lines (cancer HeLa and PC-3, and normal HaCaT
      lines), suitably chosen for their different expressions of folate binding
      proteins. The nanovector, indeed, binds much more efficiently on cancer cell
      lines than on normal ones, resulting in a higher SERS signal measured on cancer
      cells. These results pave the way for applications in single cell diagnostics
      and, potentially, in theranostics.

PMID- 27714136
TI  - Parametrization of nanoparticles: development of full-particle nanodescriptors.
AB  - While metal oxide nanoparticles (NPs) are one of the most commonly used
      nanomaterials, the theoretical models used to analyze and predict their behavior
      have been mostly based on just the chemical composition or the extrapolation from
      small metal oxide clusters' calculations. In this study, a set of novel,
      theoretical full-particle descriptors for modeling, grouping or read-across of
      metal oxide NP properties and biological activity was developed based on the
      force-field calculation of the potential energies of whole NPs. The capability of
      these nanodescriptors to group the nanomaterials acoording to their biological
      activity was demonstrated by Principal Component Analysis (PCA). The grouping
      provided by the PCA approach was found to be in good accordance with the algal
      growth inhibition data of well characterized nanoparticles, synthesized and
      measured inside the consortia of the EU 7FP framework MODERN project.

PMID- 27714137
TI  - Confinement of a beta-barrel protein in nanoperforated free-standing
      nanomembranes for ion transport.
AB  - Bioinspired free-standing nanomembranes (FSNMs) for selective ion transport have
      been tailored by immobilizing the Omp2a beta-barrel membrane protein inside
      nanoperforations created in flexible poly(lactic acid) (PLA) nanomembranes.
      Perforated PLA FSNMs have been prepared by spin-coating a 99 : 1 PLA : poly(vinyl
      alcohol) mixture, and through a phase segregation process nanofeatures with
      dimensions similar to the entire nanomembrane thickness (~110 nm) were induced.
      These nanofeatures have subsequently been transformed into nanoperforations
      (diameter: ~51 nm) by selective solvent etching. The protein confined inside the
      nanopores of PLA FSNMs preserves the beta-barrel structure and organizes in ovoid
      aggregates. The transport properties of Na+, K+, and Ca2+ across non-perforated
      PLA, nanoperforated PLA, and Omp2a-filled nanoperforated PLA have been monitored
      by measuring the nanomembrane resistance with electrochemical impedance
      spectroscopy (EIS). The incorporation of nanoperforations enhances the transport
      of ions across PLA nanomembranes, whereas the functionality of immobilized Omp2a
      is essential to exhibit effects similar to those observed in biological
      nanomembranes. Indeed, Omp2a-filled nanoperforated PLA nanomembranes exhibit
      stronger affinity towards Na+ and Ca2+ ions than towards K+. In summary, this
      work provides a novel bioinspired strategy to develop mechanically stable and
      flexible FSNMs with channels for ion transport, which are precisely located
      inside artificial nanoperforations, thus holding great potential for applications
      in biofiltration and biosensing.

PMID- 27714138
TI  - A facile hybrid 'flow and batch' access to substituted 3,4-dihydro-2H
      benzo[b][1,4]oxazinones.
AB  - We describe a simple flow chemistry approach to libraries of ethyl 3-oxo-2
      (substituted-phenylamino)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylates (12a
      l) and N-ethyl-3-oxo-2-(substituted-phenylamino)-3,4-dihydro-2H
      benzo[b][1,4]oxazine-6-carboxamides (13a-l) in 38-87% yields. This scaffold is
      poorly described in the chemical literature. Screening against a panel of 11
      cancer and one normal cell line showed that the amide linked library 13a-l was
      devoid of toxicity. Whereas the ester linked analogues 12b, 12c, 12g, 12j and 12l
      were highly cytotoxic with growth inhibition (GI50) values from 0.34 to >50 MUM
      across all cell lines, with the 2-OH-Ph substituted 12l analogue presenting with
      sub-micromolar potency against the A2780 (ovarian; 0.34 +/- 0.04 MUM), BEC-2
      (glioblastoma; 0.35 +/- 0.06 MUM), MIA (pancreas; 0.91 +/- 0.054 MUM) and SMA
      (murine glioblastoma; 0.77 +/- 0.029 MUM) carcinoma cell lines. Interestingly,
      the U87 glioblastoma cell line showed inherent resistance to growth inhibition by
      all analogues (GI50 32 to >50 MUM) while the A2780 cells were highly sensitive
      (GI50 3.8-0.34 MUM), suggesting that the analogues developed herein may be
      valuable lead compounds for the development of ovarian carcinoma specific
      cytotoxic agents. The differences in amide versus ester cytotoxicity was
      consitent with esterase cleaveage to release the cytotoxic warhead.

PMID- 27714139
TI  - Catalyst-free bottom-up growth of graphene nanofeatures along with molecular
      templates on dielectric substrates.
AB  - Synthesis of graphene nanostructures has been investigated to provide outstanding
      properties for various applications. Herein, we report molecular thin film
      assisted growth of graphene into nanofeatures such as nanoribbons and nanoporous
      sheets along with a predetermined molecular orientation on dielectric substrates
      without metal catalysts. A Langmuir-Blodgett (LB) method was used for the
      formation of the molecularly patterned SiO2 substrates with ferric stearate
      layers, which acted as a template for the directional growth of the polypyrrole
      graphene precursor. The nanofeatures of the graphene were determined by the
      number of ferric stearate layers (e.g., nanoribbons from multiple layers and
      nanoporous sheets from a single layer). The graphene nanoribbons (GNRs)
      containing pyrrolic N enriched edges exhibited a p-type semiconducting behavior,
      whereas the nanoporous graphene sheets containing inhomogeneous pores and
      graphitic N enriched basal planes exhibited the typical electronic transport of
      nitrogen-doped graphene. Our approaches provide two central methods for graphene
      synthesis such as bottom-up and direct processes for the future development of
      graphene nanoelectronics.

PMID- 27714140
TI  - Self-assembly of the full-length amyloid Abeta42 protein in dimers.
AB  - The self-assembly of amyloid (Abeta) proteins into nano-aggregates is a hallmark
      of Alzheimer's disease (AD) development, yet the mechanism of how disordered
      monomers assemble into aggregates remains elusive. Here, we applied long-time
      molecular dynamics simulations to fully characterize the assembly of Abeta42
      monomers into dimers. Monomers undergo conformational changes during their
      interaction, but the resulting dimer structures do not resemble those found in
      fibril structures. To identify natural conformations of dimers among a set of
      simulated ones, validation approaches were developed and applied, and a subset of
      dimer conformations were characterized. These dimers do not contain long beta
      strands that are usually found in fibrils. The dimers are stabilized primarily by
      interactions within the central hydrophobic regions and the C-terminal regions,
      with a contribution from local hydrogen bonding. The dimers are dynamic, as
      evidenced by the existence of a set of conformations and by the quantitative
      analyses of the dimer dissociation process.

PMID- 27714141
TI  - Vertical nanocolumn-assisted pluripotent stem cell colony formation with minimal
      cell-penetration.
AB  - The biological applications of vertical nanostructures mostly rely on their
      intracellular accessibility through the cellular membrane by promoting cell-to
      nanostructure interactions. Herein, we report a seemingly counter-intuitive
      approach for the spontaneous formation of mouse induced pluripotent stem cell
      (iPSC)-derived three-dimensional spherical colonies with unlimited self-renewal
      and differentiation potential. The comprehensive analyses of iPSCs cultured on
      vertical silicon nanocolumn arrays (vSNAs) with various nanocolumn geometries
      show reduced cell-to-substrate adhesion and enhanced cell-to-cell interactions
      under optimized vSNA conditions, successfully accommodating the spontaneous
      production of iPSC-derived spherical colonies. Remarkably, these colonies which
      were only minimally penetrated by and thereby easily harvested from wafer-sized
      vSNAs display a substantial increase in pluripotency marker expression and
      successfully differentiate into three germ layers. Our vSNAs capable of large
      scale fabrication, efficient for spherical colony formation, and reusable for
      multiple iPSC culture could serve as a broad-impact culture platform for stem
      cell research.

PMID- 27714142
TI  - Synthesis of graphene nanoribbons with a defined mixed edge-site sequence by
      surface assisted polymerization of (1,6)-dibromopyrene on Ag(110).
AB  - By a combination of scanning tunneling microscopy, X-ray spectroscopic techniques
      and density functional theory calculations, we prove the formation of extended
      patterns of parallel, graphene nanoribbons with alternate zig-zag and armchair
      edges and selected width by surface-assisted Ullmann coupling polymerization and
      dehydrogenation of 1,6-dibromopyrene (C16H8Br2). Besides the relevance of these
      nanostructures for their possible application in nanodevices, we demonstrate the
      peculiarity of halogenated pyrene derivatives for the formation of nanoribbons,
      in particular on Ag(110). These results open the possibility of tuning the shape
      and dimension of nanoribbons (and hence the correlated electronic properties) by
      choosing suitably tailored or on-purpose designed molecular precursors.

PMID- 27714143
TI  - A fluorescent ELISA based on the enzyme-triggered synthesis of poly(thymine)
      templated copper nanoparticles.
AB  - Inspired by the ALP-triggered hydrolysis of the substrate ascorbic acid 2
      phosphate as well as the product ascorbate-controlled generation of polyT-CuNPs
      with bright red fluorescence, we have developed a novel, selective and sensitive
      fluorescence turn-on assay for ALP activity sensing. Based on the conventional
      ELISA platform and commercially available antibody-ALP conjugates, an
      unconventional fluorescent ELISA system has been rationally developed and
      successfully applied in the quantitative measurement of model antigen proteins
      using fluorescence spectroscopy and a naked-eye readout under ultraviolet light.

PMID- 27714144
TI  - Superparamagnetic anisotropic nano-assemblies with longer blood circulation in
      vivo: a highly efficient drug delivery carrier for leukemia therapy.
AB  - Leukemia, unlike solid tumors, has no definite shape and spreads throughout the
      whole circulatory system, therefore the therapy of leukemia requires medication
      to stay longer in the circulatory system. Anisotropic nanoparticles, showing
      longer blood circulating life than that of isotropic nanoparticles reported in
      previous research, meet the demands of leukemia therapy. Based on this strategy,
      superparamagnetic anisotropic nano-assemblies (SANs) were fabricated and loaded
      with vincristine (VCR) to form VCR-SANs. When compared to the same dose of VCR
      loaded isotropic nano-assemblies (SINs), the decrease in the leukocytes count and
      the positive expression ratio of CD13 in the VCR-SANs group were 19.38% and
      16.4%, respectively, which indicated the improved anti-leukemia activity of the
      VCR-SANs. From the results of the pharmacokinetics study, the VCR-SANs remarkably
      held the amount of drug removed from the whole body per unit time half of the
      isotropic group and the concentration of drug in blood plasma against time was
      2.1 times the isotropic group, demonstrating the rapid and sustained release
      behavior and longer blood circulation when combined with the results of in vivo
      tissue distribution studies. In summary, anisotropic nano-assemblies were found
      to be more promising than isotropic nano-assemblies via our in vivo and in vitro
      examinations.

PMID- 27714145
TI  - Plasmonic photo-current in freestanding monolayered gold nanoparticle membranes.
AB  - We report on photo-current generation in freestanding monolayered gold
      nanoparticle membranes excited by using a focused laser beam. The absence of a
      substrate leads to a 50% increase of the photo-current at the surface plasmon
      resonance. This current is attributed to a combination of trap state dynamics and
      bolometric effects in a nanocomposite medium yielding a temperature rise of 40 K.

PMID- 27714146
TI  - A hybrid MoS2 nanosheet-CdSe nanocrystal phototransistor with a fast
      photoresponse.
AB  - 2-Dimensional (2D) and 0-dimensional (0D) hybrid nanostructures have been
      reported as promising new systems for highly-sensitive and wavelength-tunable
      photodetectors. Although the performance of hybrid photodetectors was enhanced by
      charge injection from 0D nanocrystals (NCs) to 2D nanosheets (NSs), the response
      time of hybrid photodetectors is still very slow due to the trapping and leakage
      of residual carriers at the interfaces of the hybrid materials. Here, we
      demonstrate a MoS2/CdSe hybrid phototransistor with enhanced responsivity of 2.5
      * 105 A W-1 and detectivity of 1.24 * 1014 Jones. In addition, the device
      exhibited a fast rise (taurise) and decay time (taudecay) of 60 ms, respectively.
      The mechanism for the improved photoresponse time has been discussed using a
      charge injection model in an n-n type heterojunction energy band diagram of
      hybrid materials.

PMID- 27714147
TI  - Carbon nanotubes stimulate synovial inflammation by inducing systemic pro
      inflammatory cytokines.
AB  - Carbon nanotubes (CNTs) have promising applications in a wide range of biomedical
      fields, including imaging, drug/gene delivery and other therapeutics; however,
      the biosafety concerns of CNTs should be addressed. To date, many reports have
      documented the toxicological effects on the cells, tissue or organs that are in
      direct contact with the tubes; however, there is limited evidence to unravel the
      secondary toxicity upon CNT treatment. Moreover, more effort is needed to gain a
      definitive understanding of the adverse outcome pathway (AOP) for CNTs, and a
      pragmatic framework for risk assessment has not been established yet. In the
      current study, we aimed to decipher the secondary toxicity to joints under CNT
      exposure. We demonstrated that carboxylated multi-wall CNTs (MWCNTs-COOH)
      significantly provoked systemic pro-inflammatory responses, leading to synovial
      inflammation within knee joints, as evidenced by the infiltration of pro
      inflammatory cells in the synovium and meniscus. Mechanistic studies showed that
      MWCNTs-COOH stimulated pro-inflammatory effects by activating macrophages, and
      the secreted pro-inflammatory cytokines primed the synoviocytes and chondrocytes,
      resulting in enhanced production of a large array of enzymes involved in
      articular cartilage degeneration, including matrix metalloproteinase (MMP)
      members and cyclooxygenase (COX) members, and increased enzymatic activity of
      MMPs was demonstrated. Blockade of the cytokines by antibodies significantly
      attenuated the production of these enzymes. Our current study thus suggests that
      there is a novel secondary toxicity of CNTs, namely a new AOP to understand the
      indirect effects of carbon nanotubes: synovial inflammation due to the alteration
      of the priming state of synoviocytes and chondrocytes under CNT-induced systemic
      inflammatory conditions.

PMID- 27714148
TI  - Selective killing of cells triggered by their mRNA signature in the presence of
      smart nanoparticles.
AB  - The design of nanoparticles that can selectively perform multiple roles is of
      utmost importance for the development of the next generation of nanoparticulate
      drug delivery systems. So far most research studies are focused on the
      customization of nanoparticulate carriers to maximize their drug loading, enhance
      their optical signature for tracking in cells or provide photo-responsive effects
      for therapeutic purposes. However, a vital requirement of the new generation of
      drug carriers must be the ability to deliver their payload selectively only to
      cells of interest rather than the majority of various cells in the vicinity. Here
      we show for the first time a new design of nanoparticulate drug carriers that can
      specifically distinguish different cell types based on their mRNA signature.
      These nanoparticles sense and efficiently kill model tumour cells by the delivery
      of an anti-cancer drug but retain their payload in cells lacking the specific
      mRNA target.

PMID- 27714149
TI  - Filter-free, junctionless structures for color sensing.
AB  - A simple structure, efficient color splitting, sufficient output of electrical
      signals, and low power consumption are the important characteristics of
      contemporary devices for color sensing. In this study, we developed filter-free,
      junctionless structures that exhibited a superior photo-thermo-electrical
      response under a low bias voltage and a short response time in milliseconds.
      Although our compact sensor had a simple single-layer trench-like aluminum (Al)
      structure, it could perform multiple functions, including light harvesting, color
      selective absorption, photo-thermo-electrical transformation, and the ability to
      collect photoinduced differences in electrical signals. This device exploited
      near-field surface plasmon resonance and cavity effects to enhance the intensity
      of the electric field and the color-selective absorption, ultimately resulting in
      significant current signals in its structured Al film. This strategy
      significantly simplifies not only the components of the color sensor but also its
      fabrication; for example, red, green, and blue color detection devices could be
      prepared simultaneously through a single lithography, etching, and deposition
      step. With its ability to provide functional filter-free, junctionless
      structures, this strategy has great potential for the production of devices that
      operate on different kinds of substrates, thereby bridging various applications
      of color sensing technologies.

PMID- 27714150
TI  - Synthesis of hybrid metal-organic frameworks of {FexMyM'1-x-y}-MIL-88B and the
      use of anions to control their structural features.
AB  - The controlled formation of metal-organic frameworks (MOFs) or coordination
      polymers (CPs) with suitable components and structural features is one of the
      most important themes in MOF research. In particular, the reliable preparation of
      hybrid MOFs containing more than two different kinds of metal ions or organic
      linkers and a comprehensive understanding of the structural flexibility of MOFs
      are the central issues for the production of MOFs with the desired properties. We
      report the synthesis of micro-sized hybrid MOF particles [also known as
      coordination polymer particles (CPPs)] containing two or three kinds of metal
      ions in each particle: {FexMyM'1-x-y}-MIL-88B (MIL stands for Materials of
      Institut Lavoisier, M and M' = Ga, Co, or Mn). Scanning electron microscopy
      images revealed the formation of well-defined uniform micro-sized hexagonal rods,
      and energy-dispersive X-ray spectroscopy and elemental mapping images verified
      the simultaneous incorporation of two or three kinds of metal ions within the
      CPPs. Interestingly, the structural features of CPPs made from MIL-88B were
      controlled by altering the anions involved in the structure. Incorporating large
      acetylacetonate anions within the structure resulted in the closed MIL-88B
      structure with a small cell volume. However, the open MIL-88B structure with a
      large cell volume was obtained when small chloride anions were incorporated. The
      intermediate semi-open MIL-88B structure was also prepared using nitrate anions.
      Three different structural forms of MIL-88B were verified by powder X-ray
      diffraction, whole pattern fitting, and thermogravimetric analysis.

PMID- 27714151
TI  - High-energy lithium-ion hybrid supercapacitors composed of hierarchical urchin
      like WO3/C anodes and MOF-derived polyhedral hollow carbon cathodes.
AB  - A lithium-ion hybrid supercapacitor (Li-HSC) comprising a Li-ion battery type
      anode and an electrochemical double layer capacitance (EDLC) type cathode has
      attracted much interest because it accomplishes a large energy density without
      compromising the power density. In this work, hierarchical carbon coated WO3
      (WO3/C) with a unique mesoporous structure and metal-organic framework derived
      nitrogen-doped carbon hollow polyhedra (MOF-NC) are prepared and adopted as the
      anode and the cathode for Li-HSCs. The hierarchical mesoporous WO3/C microspheres
      assembled by radially oriented WO3/C nanorods along the (001) plane enable
      effective Li+ insertion, thus exhibit high capacity, excellent rate performance
      and a long cycling life due to their high Li+ conductivity, electronic
      conductivity and structural robustness. The WO3/C structure shows a reversible
      specific capacity of 508 mA h g-1 at a 0.1 C rate (1 C = 696 mA h g-1) after 160
      discharging-charging cycles with excellent rate capability. The MOF-NC achieved
      the specific capacity of 269.9 F g-1 at a current density of 0.2 A g-1. At a high
      current density of 6 A g-1, 92.4% of the initial capacity could be retained after
      2000 discharging-charging cycles, suggesting excellent cycle stability. The Li
      HSC comprising a WO3/C anode and a MOF-NC cathode boasts a large energy density
      of 159.97 W h kg-1 at a power density of 173.6 W kg-1 and 88.3% of the capacity
      is retained at a current density of 5 A g-1 after 3000 charging-discharging
      cycles, which are better than those previously reported for Li-HSCs. The high
      energy and power densities of the Li-HSCs of WO3/C//MOF-NC render large potential
      in energy storage.

PMID- 27714152
TI  - Slow and fast absorption saturation of black phosphorus: experiment and
      modelling.
AB  - According to the excited-state decay time, a slow saturable absorber model was
      employed to obtain the ground-state absorption and excited-state absorption cross
      sections sigmags and sigmaes of black phosphorus (BP) nanosheets, which are (1.25
      +/- 0.07) * 10-16 cm2 and (2.97 +/- 0.21) * 10-17 cm2 at 515 nm, and (5.95 +/-
      0.17) * 10-18 cm2 and (5.19 +/- 0.71) * 10-19 cm2 at 1030 nm, respectively. In
      comparison, the sigmags and sigmaes of MoS2 and graphene were also obtained with
      the same model. The ratio sigmaes/sigmags of BP is the smallest (only 0.24 +/-
      0.03 at 515 nm and 0.09 +/- 0.01 at 1030 nm) among the three two-dimensional
      layered materials both at 515 nm and 1030 nm. Relatively large ground-state
      transition probability and weak loss of excited-state absorption result in good
      saturable absorption performance. In comparison with MoS2 and graphene, the much
      lower saturation intensity of BP can be well explained from this perspective.

PMID- 27714153
TI  - Self-immolative versatile fluorogenic probes for screening of hydrolytic enzyme
      activity.
AB  - Enzyme triggered probes with a self-immolative linker for rapid and sensitive
      hydrolase detection through a cascade reaction have been reported. Their utility
      was proved by the preparation of three model compounds and their evaluation as
      enzyme substrates and demonstration of their applicability as fluorogenic probes
      for screening lipase, esterase and protease activities. These probes represent a
      new class of fluorogenic compounds, are stable under aqueous conditions and not
      susceptible to nonspecific degradation. The utilization of the carbamate
      cleavable linkage in a probe structure allows moving away of the bulky
      fluorophore from the enzyme recognition unit and targets different classes of
      enzymes with the same substrate.

PMID- 27714154
TI  - Characterization of nanoporous structures: from three dimensions to two
      dimensions.
AB  - The scanning electron microscope (SEM) has revealed a colorful three-dimensional
      world due to its great depth of field. However, the abundance of structural
      information imposes tough challenges to quantitative image analysis. In the
      current investigation, we developed a SEM-image polishing (SIP) based
      quantitative SEM-image analysis (QSIA) technique. As an example, QSIA was
      employed to characterize nanoporous silica. The results confirmed that the
      nanoporous silica samples, processed via sol-gel methods, were single-parameter,
      with the pore size being the only variable. The QSIA technique may pave the way
      to fast and accurate data mining of nanoscaled materials.

PMID- 27714155
TI  - Chemical synthesis and enzymatic properties of RNase A analogues designed to
      enhance second-step catalytic activity.
AB  - In this paper, we have used total chemical synthesis of RNase A analogues in
      order to probe the molecular basis of enzyme catalysis. Our goal was to
      obligately fill the adenine-binding pocket on the enzyme molecule, and to thus
      pre-orient the imidazole side chain of His119 in its catalytically productive
      orientation. Two designed analogues of the RNase A protein molecule that
      contained an adenine moiety covalently bound to distinct amino acid side chains
      adjacent to the adenine binding pocket were prepared. A crystal structure of one
      analogue was determined at 2.3 A resolution. Kinetic data for RNA
      transphosporylation and 2',3' cyclic mononucleotide hydrolysis were acquired for
      the adenine-containing RNase A analogue proteins. As anticipated, the presence of
      a covalently attached adenine on the enzyme molecule decreased the rate of
      transphosphorylation and increased the rate of hydrolysis, although the magnitude
      of the effects was small. This work illustrates the use of total protein
      synthesis to investigate the chemistry of enzyme catalysis in ways not possible
      through traditional biochemistry or molecular biology.

PMID- 27714156
TI  - A simple melting-diffusing-reacting strategy to fabricate S/NiS2-C for lithium
      sulfur batteries.
AB  - S/NiS2-C composites were fabricated using a sample melting-diffusing-reacting
      strategy. When the elemental sulfur content in the composite is 54.9 wt%, it
      shows good cyclic performance and delivers a specific capacity of 730 mA h g-1
      after 200 cycles at 0.5 C and 544 mA h g-1 after 500 cycles at 2 C. The elemental
      sulfur content can be adjusted, and when the elemental sulfur content is
      increased to 64.8 wt% and 76.0 wt%, the cathodes can maintain a stable cyclic
      capacity of 386 and 312 mA h g-1 after being discharged/charged at 2 C for 500
      cycles respectively. The carbon structure and the uniformly distributed nickel
      disulfide in the S/NiS2-C composites efficiently stabilizes the polysulfides and
      also facilitates the conversion of electrochemical reactions.

PMID- 27714157
TI  - A direct assay of butyrylcholinesterase activity using a fluorescent substrate.
AB  - In this study, we report a direct fluorometric assay for butyrylcholinesterase
      (BChE) activity and screening of its inhibitor, using a fluorescent substrate. 2
      (2-(5,6-Dimethoxy-1,3-dioxoisoindolin-2-yl)acetoxy)-N,N,N-trimethylethan-1
      ammonium iodide (1) was hydrolyzed by BChE, and its fluorescence was quenched by
      an intramolecular photoinduced electron transfer process. The resulting change in
      fluorescence provided a facile method for real-time BChE activity testing.
      Remarkably, 1 was selectively hydrolyzed by BChE, even in the presence of excess
      acetylcholinesterase, thereby facilitating the specific monitoring of BChE
      activity. This assay method is also useful for screening potential BChE
      inhibitors. Given its simplicity, selectivity, and higher assay speed, this
      method may be extended to high-throughput screening of BChE inhibitors and
      relevant drug discovery.

PMID- 27714158
TI  - The role of the crystalline face in the ordering of 6-mercaptopurine self
      assembled monolayers on gold.
AB  - Well-ordered molecular films play an important role in nanotechnology, from
      device fabrication to surface patterning. Self-assembled monolayers (SAMs) of 6
      mercaptopurine (6MP) on the Au(100)-(1 * 1) and Au(111)-(1 * 1) have been used to
      understand the interplay of molecule-substrate interactions for heterocyclic
      thiols capable of binding to the surface by two anchors, which spontaneously form
      a highly disordered film on Au(111). Our results reveal that for the same surface
      coverage the simple change of the substrate from Au(111)-(1 * 1) to Au(100)-(1 *
      1) eliminates molecular disorder and yields well-ordered SAMs. We discuss these
      findings in terms of differences in the surface mobility of 6MP species on these
      surfaces, the energetics of the adsorption sites, and the number of degrees of
      freedom of these substrates for a molecule with reduced surface mobility
      resulting from its two surface anchors. These results reveal the presence of
      subtle molecule-substrate interactions involving the heteroatom that drastically
      alter SAM properties and therefore strongly impact on our ability to control
      physical properties and to build devices at the nanoscale.

PMID- 27714159
TI  - Switch on the high thermal conductivity of graphene paper.
AB  - This work reports on the discovery of a high thermal conductivity (kappa) switch
      on phenomenon in high purity graphene paper (GP) when its temperature is reduced
      from room temperature down to 10 K. The kappa after switch-on (1732 to 3013 W m-1
      K-1) is 4-8 times that before switch-on. The triggering temperature is 245-260 K.
      The switch-on behavior is attributed to the thermal expansion mismatch between
      pure graphene flakes and impurity-embedded flakes. This is confirmed by the
      switch behavior of the temperature coefficient of resistance. Before switch-on,
      the interactions between pure graphene flakes and surrounding impurity-embedded
      flakes efficiently suppress phonon transport in GP. After switch-on, the
      structure separation frees the pure graphene flakes from the impurity-embedded
      neighbors, leading to a several-fold kappa increase. The measured kappa before
      and after switch-on is consistent with the literature reported kappa values of
      supported and suspended graphene. By conducting comparison studies with pyrolytic
      graphite, graphene oxide paper and partly reduced graphene paper, the whole
      physical picture is illustrated clearly. The thermal expansion induced switch-on
      is feasible only for high purity GP materials. This finding points out a novel
      way to switch on/off the thermal conductivity of graphene paper based on
      substrate-phonon scattering.

PMID- 27714160
TI  - A novel and highly efficient earth-abundant Cu3P with TiO2 "P-N" heterojunction
      nanophotocatalyst for hydrogen evolution from water.
AB  - Semiconductor-based photocatalytic hydrogen (H2) evolution from water is of great
      importance for solar-to-chemical conversion processes to boost and promote the
      future hydrogen economy. Here, for the first time, we demonstrate that p-Cu3P
      coupled with n-TiO2 forms a novel hybrid structure which accelerates electron
      hole pair separation and transfer for improved photocatalytic H2-evolution
      activity. The rate of H2 evolution of the optimized Cu3P/TiO2 (7940 MUmol h-1 g
      1) is 11 times higher than that of bare TiO2, with an apparent quantum efficiency
      (AQE) of 4.6%. This work may provide more insight into the synthesis of novel
      phosphide-based hybrid materials with high photocatalytic H2-evolution activity
      and sufficient stability for solar-to-chemical conversion and utilization.

PMID- 27714161
TI  - Inflammation-sensitive in situ smart scaffolding for regenerative medicine.
AB  - To cope with the rapid evolution of the tissue engineering field, it is now
      essential to incorporate the use of on-site responsive scaffolds. Therefore, it
      is of utmost importance to find new 'Intelligent' biomaterials that can respond
      to the physicochemical changes in the microenvironment. In this present report,
      we have developed biocompatible stimuli responsive polyaniline-multiwalled carbon
      nanotube/poly(N-isopropylacrylamide), (PANI-MWCNT/PNIPAm) composite nanofiber
      networks and demonstrated the physiological temperature coordinated cell grafting
      phenomenon on its surface. The composite nanofibers were prepared by a two-step
      process initiated with an assisted in situ polymerization followed by
      electrospinning. To obtain a smooth surface in individual nanofibers with the
      thinnest diameter, the component ratios and electrospinning conditions were
      optimized. The temperature-gated rearrangements of the molecular structure are
      characterized by FTIR spectroscopy with simultaneous macromolecular architecture
      changes reflected on the surface morphology, average diameter and pore size as
      determined by scanning electron microscopy. The stimuli responsiveness of the
      nanofibers has first been optimized with computational modeling of temperature
      sensitive components (coil-like and globular conformations) to tune the mechanism
      for temperature dependent interaction during in situ scaffolding with the cell
      membrane. The nanofiber networks show excellent biocompatibility, tested with
      fibroblasts and also show excellent sensitivity to inflammation to combat loco
      regional acidosis that delay the wound healing process by an in vitro model that
      has been developed for testing the proposed responsiveness of the composite
      nanofiber networks. Cellular adhesion and detachment are regulated through
      physiological temperature and show normal proliferation of the grafted cells on
      the composite nanofibers. Thus, we report for the first time, the development of
      physiological temperature gated inflammation-sensitive smart biomaterials for
      advanced tissue regeneration and regenerative medicine.

PMID- 27714162
TI  - Correction: In situ growth of fluorescent silicon nanocrystals in a monolithic
      microcapsule as a photostable, versatile platform.
AB  - Correction for 'In situ growth of fluorescent silicon nanocrystals in a
      monolithic microcapsule as a photostable, versatile platform' by Guixian Zhu, et
      al., Nanoscale, 2016, 8, 15645-15657.

PMID- 27714163
TI  - A modular clamp-like mechanism to regulate the activity of nucleic-acid target
      responsive nanoswitches with external activators.
AB  - Here we demonstrate a general and modular approach to regulate the activity of
      target-responsive DNA-based nanoswitches. We do so by coupling together two DNA
      based responsive elements: a triplex-forming clamp-like probe able to bind a
      specific DNA sequence and a split aptamer selected to bind a small molecule. In
      the presence of the specific target of one of the above responsive elements, the
      nanoswitch partially folds and its ability to bind the second target is restored.
      With this approach we can finely modulate the affinity of both DNA-recognition
      elements and aptamers using an external ligand. The modular nature of our
      strategy makes it easily generalizable to different DNA based recognition
      elements. As a demonstration of this we successfully designed five different DNA
      nanoswitches whose responsiveness can be regulated by different molecular
      effectors and targets. The convenience with which this mechanism is designed
      suggests that it may prove a useful tool by which sensors, genetic networks and
      other biotechnology devices employing nucleic-acid based receptors can be
      controlled with an external input.

PMID- 27714164
TI  - Effect of temperature on the viscoelastic properties of nano-confined liquid
      mixtures.
AB  - The behaviour of fluids confined in nanoscale gaps plays a central role in
      molecular science and nanofluidics, with applications ranging from biological
      function to multiscale printing, osmosis and filtration, lab-on-chip technology
      and friction reduction. Here atomic force microscopy is used to shear five
      different mixtures of hexadecane and squalane confined between the tip apex and
      atomically flat graphite. The shearing amplitudes are typically <2 nm, hence
      reflecting highly localised information at the interface. The evolution of each
      mixture's viscoelastic properties is studied as a function of temperature,
      between 20  degrees C and 100  degrees C. The results, complemented by sub
      nanometre resolution images of the interface, show that spatial organisation of
      the liquid molecules at the surface of graphite largely dominates the
      measurements. Squalane presents a higher effective affinity for the surface by
      forming a robust self-assembled layer in all mixtures. This results in a step
      like change of the viscous and elastic response of the confined liquid as the
      confining pressure increases. In contrast, measurements in pure hexadecane show a
      continuous and linear increase in the apparent viscosity with pressure at all
      temperatures. This is interpreted as a more fragile interfacial layer and images
      show that it can be completely removed at high temperatures. Depending on the
      mixture composition, measurements can be strongly location-dependent which
      suggests molecular clustering and nanoscale phase separation at the interface.

PMID- 27714165
TI  - Plasmonic ELISA based on the controlled growth of silver nanoparticles.
AB  - Herein, we demonstrate a plasmonic ELISA based on the alkaline phosphatase (ALP)
      mediated growth of silver nanoparticles (AgNPs) for the sensitive, rapid, and
      naked-eye detection of cancer biomarkers in clinical serum samples. This approach
      was used to measure the low-abundance alpha fetal protein (AFP) in clinical sera,
      which demonstrates its great capability in the differentiation of cancers and
      evaluation of therapeutic responses. Impressively, the readout of the plasmonic
      assay depends on the rapid formation of Ag colloidal solutions with various
      degrees of yellow color, which can be distinguished by the naked eye, without the
      need for sophisticated platforms. The limit of detection of the plasmonic ELISA
      for alpha fetal protein (AFP) can be as low as 0.23 ng mL-1, which is
      approximately 10 folds lower than that of conventional ELISA. This plasmonic
      ELISA opens a new avenue for the early detection of cancers and monitoring of
      cancer reoccurrence especially in resource-poor regions where convenient
      diagnostic tools are highly desirable.

PMID- 27714166
TI  - Synthesis, properties and applications of 2D layered MIIIXVI (M = Ga, In; X = S,
      Se, Te) materials.
AB  - Group III-VI compounds MIIIXVI (M = Ga, In; X = S, Se, Te) are one class of
      important 2D layered materials and are currently attracting increasing interest
      due to their unique electronic and optoelectronic properties and their great
      potential applications in various other fields. Similar to 2D layered transition
      metal dichalcogenides (TMDs), MIIIXVI also have the significant merits of
      ultrathin thickness, ultrahigh surface-to-volume ratio, and high compatibility
      with flexible devices. More impressively, in contrast with TMDCs, MIIIXVI
      demonstrate many superior properties, such as direct band gap electronic
      structure, high carrier mobility, rare p-type electronic behaviors, high charge
      density, and so on. These unique characteristics cause high-performance device
      applications in electronics, optoelectronics, and optics. In this review, we aim
      to provide a summary of the state-of-the-art of research activities in 2D layered
      MIIIXVI materials. The scope of the review covers the synthesis and properties of
      2D layered MIIIXVI materials and their van der Waals heterostructures. We
      especially focus on the applications in electronics and optoelectronics.
      Moreover, the review concludes with some perspectives on future developments in
      this field.

PMID- 27714167
TI  - 3D-branched hierarchical 3C-SiC/ZnO heterostructures for high-performance
      photodetectors.
AB  - The ultra-sensitive photodetection of different wavelengths holds promising
      applications in high-performance optoelectronic devices and it requires an
      efficient and suitable semiconductor unit. Herein, we demonstrated the designable
      synthesis of 3D-branched hierarchical 3C-SiC/ZnO heterostructures by a three-step
      process and their assembling into an ultrasensitive photodetector. Microstructure
      analyses using high-resolution transmission electron microscopy reveal that the
      hierarchical 3C-SiC/ZnO heterostructure is composed of single-crystal 3C-SiC
      nanowires as a central stem and numerous well-aligned single-crystalline ZnO
      nanorods as branch shells. Optoelectronic tests on the 3C-SiC/ZnO heterostructure
      photodetector verify the outstanding photo-detection performance with an
      ultrahigh EQE (1.69 * 108%), a superior photoresponsivity (4.8 * 105 A W-1), a
      very fast response time (a rise time of 40 ms and a decay time of 60 ms), a high
      photo-dark current ratio of 187.8 and an excellent photocurrent stability and
      reproducibility, which is significantly advantageous or comparable to those of
      ZnO and other inorganic semiconductor nanostructure based photodetectors. To
      understand the excellent photodetection of hierarchical 3C-SiC/ZnO
      heterostructures, a band-gap energy diagram describing the photogenerated
      electron transport process is plotted and the corresponding mechanism is
      discussed. The strategy proposed in the present work will open up more
      opportunities for the design and boost of ultra-sensitive photodetectors based on
      semiconductor heterostructures.

PMID- 27714168
TI  - Targeted SERS nanosensors measure physicochemical gradients and free energy
      changes in live 3D tumor spheroids.
AB  - Use of multicellular tumor spheroids (MTS) to investigate therapies has gained
      impetus because they have potential to mimic factors including zonation, hypoxia
      and drug-resistance. However, analysis remains difficult and often destroys 3D
      integrity. Here we report an optical technique using targeted nanosensors that
      allows in situ 3D mapping of redox potential gradients whilst retaining MTS
      morphology and function. The magnitude of the redox potential gradient can be
      quantified as a free energy difference (DeltaG) and used as a measurement of MTS
      viability. We found that by delivering different doses of radiotherapy to MTS we
      could correlate loss of DeltaG with increasing therapeutic dose. In addition, we
      found that resistance to drug therapy was indicated by an increase in DeltaG.
      This robust and reproducible technique allows interrogation of an in vitro tumor
      model's bioenergetic response to therapy, indicating its potential as a tool for
      therapy development.

PMID- 27714169
TI  - Traceless reductive ligation at a tryptophan site: a facile access to beta
      hydroxytryptophan appended peptides.
AB  - An efficient methodology for cysteine-free ligation at a tryptophan (Trp) site is
      described. A chemically active scaffold, beta-hydroxy-alpha-azidotryptophan, has
      been synthesized and explored towards the synthesis of a series of beta
      hydroxytryptophan appended native peptides in good yields via one-pot reductive
      traceless ligation of beta-O-peptidyl-alpha-azidotryptophan involving an O -> N
      peptidyl transfer strategy. Pre-organized conformational analysis and reaction
      energy pathway based theoretical studies further supported the experimental
      findings on the chemical structure stability of ligated products.

PMID- 27714170
TI  - Ultrastable nitrogen-doped carbon encapsulating molybdenum phosphide
      nanoparticles as highly efficient electrocatalyst for hydrogen generation.
AB  - There is a crucial demand for cost-effective hydrogen evolution reaction (HER)
      catalysts towards future renewable energy systems, and the development of such
      catalysts operating under all pH conditions still remains a challenging task. In
      this work, a one-step facile approach to synthesizing nitrogen-doped carbon
      encapsulating molybdenum phosphide nanoparticles (MoP NPs@NC) is introduced by
      using ammonium molybdate, ammonium dihydrogen phosphate and melamine as
      precursor. Benefitting from structural advantages, including ultrasmall
      nanoparticles, large exposed surface area and fast charge transfer, MoP NPs@NC
      exhibits excellent HER catalytic activities with small overpotentials at all pH
      values (j = 10 mA cm-2 at eta = 115, 136 and 80 mV in 0.5 M H2SO4, 1.0 M
      phosphate buffer solution and 1.0 M KOH, respectively.). Meanwhile, the high
      catalytic activities of MoP NPs@NC under both neutral and basic conditions have
      never been achieved before for molybdenum phosphide-based catalysts.
      Additionally, the encapsulation by N-doped carbon effectively prevents the MoP
      NPs from corrosion, exhibiting nearly unfading stability after 100 h testing in
      0.5 M H2SO4. Thus, our work could pave a new avenue for unprecedented design and
      fabrication of novel low-cost metal phosphide electrocatalysts encapsulated by N
      doped carbon.

PMID- 27714171
TI  - Synthesis and antitumor activity of novel N-substituted tetrahydro-beta-carboline
      imidazolium salt derivatives.
AB  - The synthesis of a series of novel N-substituted tetrahydro-beta-carboline
      imidazolium salt derivatives is presented. The biological properties of the
      compounds were evaluated in vitro against a panel of human tumor cell lines. The
      results suggest that the benzimidazole ring and 1-(naphthalen-2-yl)ethan-1-one or
      2-naphthylmethyl substituent at the imidazolyl-3-position were vital for
      modulating cytotoxic activity. Compound 41 was observed as a potent derivative
      with IC50 values of 3.24-8.78 MUM and exhibited cytotoxic activity selectively
      against HL-60, A-549 and MCF-7 cell lines. Meanwhile, high inhibitory activities
      selectively against HL-60 and MCF-7 cell lines were observed for compound 51.
      Moreover, compound 51 was able to induce G1 phase cell cycle arrest and apoptosis
      in MCF-7 cells. The cytotoxicity of compound 51 against human normal lung
      epithelial cell line BEAS-2B was further evaluated.

PMID- 27714172
TI  - Supramolecular metalloglycodendrimers selectively modulate lectin binding and
      delivery of Ru(ii) complexes into mammalian cells.
AB  - A host-guest interaction between Ru(ii)-complexes and sugar-capped beta
      cyclodextrin was employed to synthesize metalloglycodendrimers. These
      glycodendrimers demonstrated selective carbohydrate-protein interactions and
      controlled the delivery of the Ru(ii) complexes into cancer cells, which may
      facilitate cell-specific apoptosis. Lectin binding assay revealed micromolar
      range IC50 values with different plant lectins. Cell viability assay and confocal
      imaging studies of Ru(ii) complexes exhibited cytotoxic activities in cancer
      cells compared to normal cells with IC50 values close to other literature Ru(ii)
      complexes. The cell death inducer was found to accumulate favorably to the
      endoplasmic reticulum (ER) and induced ER stress in cells. The upregulation of
      CHOP, caspase-3 and caspase-12 disturbed the ER morphology initiating the
      apoptosis pathway.

PMID- 27714173
TI  - Near-infrared emissive carbon dots for two-photon fluorescence bioimaging.
AB  - Fluorescent probes with both excitation and emission in the near-infrared (NIR)
      region are highly attractive in the field of bioimaging. Herein, NIR emissive
      carbon dots (CDs, lambdamax = 683 nm) capable of excitation with a NIR
      femtosecond pulse laser (850 nm) are reported for the first time. The NIR CDs
      also hold a variety of superior features including excellent water
      dispersibility, narrow emission bands, and high quantum yields (QY = 16.8%).
      Further studies reveal that the emission of the NIR CDs derives predominantly
      from the surface molecular state mechanism. More interestingly, the NIR CDs are
      verified to have very low cytotoxicity and show capabilities for two-photon
      fluorescence bioimaging. Finally, the NIR CDs are shown to be easily modified
      with fluorescein isothiocyanate (FITC) and moved into living cells. These
      findings demonstrate that the as-prepared NIR CDs could not only be potentially
      employed for deep-tissue two-photon bioimaging, but also used as an effective
      carrier for delivery of drugs that can't (or hardly) enter into living cells
      directly.

PMID- 27714174
TI  - FT-IR and NMR structural markers for thiazole-based gamma-peptide foldamers.
AB  - Nuclear magnetic resonance (NMR) spectroscopy has been established as a potent
      method for the determination of foldamer structures in solution. However, the NMR
      techniques could be limited by averaging, so additional experimental techniques
      are often needed to fully endorse the folding properties of a sequence. We have
      recently demonstrated that oligo-gamma-peptides composed of 4-amino(methyl)-1,3
      thiazole-5-carboxylic acids (ATCs) adopt an original helical fold stabilized by
      hydrogen bonds forming C9 pseudocycles. The main objective of the present work is
      to reinvestigate the folding of ATC oligomer 1 in order to identify reliable FT
      IR and NMR structural markers that are of value for tracking the degree of
      organization of ATC-based peptides.

PMID- 27714175
TI  - Inherent N,O-containing carbon frameworks as electrode materials for high
      performance supercapacitors.
AB  - N,O-Containing micropore-dominated materials have been developed successfully via
      temperature-dependent cross-linking of 4,4'-(dioxo-diphenyl-2,3,6,7
      tetraazaanthracenediyl)dibenzonitrile (DPDN) monomers. By employing a molecular
      engineering strategy, we have designed and synthesized a series of porous
      heteroatom-containing carbon frameworks (PHCFs), in which nitrogen and oxygen
      heteroatoms are distributed homogeneously throughout the whole framework at the
      atomic level, which can ensure the stability of its electrical properties. The as
      made PHCFs@550 exhibits a high specific capacitance of 378 F g-1, with an
      excellent long cycling life, including excellent cycling stability (capacitance
      retention of ca. 120% over 20 000 cycles). Moreover, the successful preparation
      of PHCFs provides new insights for the fabrication of nitrogen and oxygen
      containing electrode materials from readily available components via a facile
      route.

PMID- 27714176
TI  - Nanoscale orbital excitations and the infrared spectrum of a molecular Mott
      insulator: A15-Cs3C60.
AB  - The quantum physics of ions and electrons behind low-energy spectra of strongly
      correlated molecular conductors, superconductors and Mott insulators is poorly
      known, yet fascinating especially in orbitally degenerate cases. The fulleride
      insulator Cs3C60 (A15), one such system, exhibits infrared (IR) spectra with low
      temperature peak features and splittings suggestive of static Jahn-Teller
      distortions with a breakdown of orbital symmetry in the molecular site. That is
      puzzling, since there is no detectable static distortion, and because the
      features and splittings disappear upon modest heating, which they should not.
      Taking advantage of the Mott-induced collapse of electronic wavefunctions from
      lattice-extended to nanoscale localized inside a caged molecular site, we show
      that the unbroken spin and orbital symmetry of the ion multiplets explains the IR
      spectrum without adjustable parameters. This demonstrates the importance of a
      fully quantum treatment of nuclear positions and orbital momenta in the Mott
      insulator sites, dynamically but not statically distorted. The observed demise of
      these features with temperature is explained by the thermal population of a
      multiplet term whose nuclear positions are essentially undistorted, but whose
      energy is very low-lying. That term is in fact a scaled-down orbital excitation
      analogous to that of other Mott insulators, with the same spin 1/2 as the ground
      state, but with a larger orbital momentum of two instead of one.

PMID- 27714177
TI  - Shape-dependent cellular behaviors and relaxivity of iron oxide-based T1 MRI
      contrast agents.
AB  - Recent research efforts about iron oxide nanoparticles has focused on the
      development of iron oxide-based T1 contrast agents for magnetic resonance imaging
      (MRI), such as ultrasmall iron oxide nanospheres (USNPs <4 nm) and ultrathin
      nanowires (NW, diameter <4 nm). In this paper, we report the cellular uptake
      behaviors of these two types of ultrasmall scale nanostructures on HepG2 cells.
      Both these two nanostructures were functionalized with tannic acid and their
      physical and chemical properties were carefully analyzed before cellular tests.
      Both USNPs and NWs exhibited strong paramagnetic signals, a property suitable for
      T1 MRI contrast agents. The distinct shapes also caused much difference in their
      cellular uptake behaviors. Specifically, the uptake of USNPs was five times
      higher than that of NWs after 72 hours incubation. The shape-dependent cellular
      uptake can potentially lead to different blood circulation times, and
      subsequently different applications of these two types of ultrasmall
      nanostructures.

PMID- 27714178
TI  - 5-Bromo-2'-deoxycytidine-a potential DNA photosensitizer.
AB  - A double-stranded oligonucleotide, 80 base pairs in length, was multiply labeled
      with 5-bromo-2'-deoxycytidine (BrdC) using polymerase chain reaction (PCR). The
      modified oligonucleotide was irradiated with 300 nm photons and its damage was
      assayed by employing DHPLC, LC-MS and denaturing polyacrylamide gel
      electrophoresis (PAGE). Two types of damage were demonstrated, namely, single
      strand breaks (SSBs) and intrastrand cross-links (ICLs); the ICLs were in the
      form of d(G^C) and d(C^C) dimers. The former species are probably formed due to
      photoinduced electron transfer between the photoexcited BrdC and the ground state
      2'-deoxyguanosine (dG), whereas the latter is a result of a cycloaddition
      reaction. Since SSBs and ICLs are potentially lethal to the cell, BrdC could be
      considered as a nucleoside with possible clinical applications.

PMID- 27714179
TI  - A one-pot synthesis of tetrazolones from acid chlorides: understanding functional
      group compatibility, and application to the late-stage functionalization of
      marketed drugs.
AB  - A one-pot and scalable synthesis of tetrazolones (tetrazol-5-ones) from acid
      chlorides using azidotrimethylsilane is presented. The reaction tolerates many
      functional groups and can furnish aryl-, heteroaryl-, alkenyl-, or alkyl
      substituted tetrazolone products in moderate to excellent yield (14-94%). No
      reduction in yield was observed when the reaction was undertaken on a larger
      scale (20-36 g). The method could be used for the late-stage functionalization of
      pharmaceuticals, to provide tetrazolone congeners of the marketed drugs aspirin,
      indomethacin, probenecid, telmisartan, bexarotene, niacin (vitamin B3), and the
      active metabolite of the recently-launched immuno-modulatory agent, BG-12
      (Tecfidera(r)). The ability of a tetrazolone group to serve as a bioisostere of a
      carboxylic acid, and to improve drug pharmacokinetic profiles is also
      highlighted.

PMID- 27714180
TI  - Radical-mediated divergent cyclization of benzamides toward perfluorinated or
      cyanated isoquinolinediones.
AB  - A simple and efficient copper-controlled divergent cyclization of benzamides,
      which leads to perfluorinated or cyanated isoquinolinediones, is developed. In
      the presence of AIBN, methacryloyl benzamides with perfluoroalkyl iodides undergo
      cascade radical addition/cyclization to afford perfluoroinated isoquinolinediones
      as the major product under metal-free conditions, whereas the use of CuI (10
      mol%) is able to redirect the cyclization to yield isoquinolinediones bearing an
      alpha-cyano quaternary carbon center. The cyclization features controllable
      divergent synthesis and a broad substrate scope as well as highly practical
      reaction conditions, thereby making this strategy a highly attractive means to
      fluorinate or cyanate isoquinolinediones.

PMID- 27714181
TI  - Correction: Composition-dependent Raman modes of Mo1-xWxS2 monolayer alloys.
AB  - Correction for 'Composition-dependent Raman modes of Mo1-xWxS2 monolayer alloys'
      by Yanfeng Chen et al., Nanoscale, 2014, 6, 2833-2839.

PMID- 27714182
TI  - 3D nest-shaped Sb2O3/RGO composite based high-performance lithium-ion batteries.
AB  - A Sb2O3/graphene composite with nest-shaped architecture has been successfully
      prepared. Compared with pure Sb2O3 materials, the Sb2O3/graphene composite
      exhibits superior electrochemical performance as an anode material in lithium-ion
      batteries, and this should be attributed to the synergistic effects of the high
      conductivity of graphene and the novel nest-shaped structure of the composite.

PMID- 27714183
TI  - TiO2 nanotubes with laterally spaced ordering enable optimized hierarchical
      structures with significantly enhanced photocatalytic H2 generation.
AB  - In the present work we grow self-organized TiO2 nanotube arrays with a defined
      and controlled regular spacing between individual nanotubes. These defined
      intertube gaps allow one to build up hierarchical 1D-branched structures,
      conformally coated on the nanotube walls using a layer by layer nanoparticle TiO2
      decoration of the individual tubes, i.e. having not only a high control over the
      TiO2 nanotube host structure but also on the harvesting layers. After optimizing
      the intertube spacing, we build host-guest arrays that show a drastically
      enhanced performance in photocatalytic H2 generation, compared to any arrangement
      of conventional TiO2 nanotubes or conventional TiO2 nanoparticle layers. We show
      this beneficial effect to be due to a combination of an increased large surface
      area (mainly provided by the nanoparticle layers) with a fast transport of the
      harvested charge within the passivated 1D nanotubes. We anticipate that this type
      of hierarchical structures based on TiO2 nanotubes with adjustable spacing will
      find even wider application, as they provide an unprecedented controllable
      combination of surface area and carrier transport.

PMID- 27714184
TI  - Functional nanocomposites with perfect nanoblending between water-soluble
      polymers and hydrophobic inorganic nanoparticles: applications to electric
      stimuli-responsive films.
AB  - There is rising demand for metal or metal oxide nanoparticle (NP)/polymer
      nanocomposite films with desired functionalities. However, it is difficult to
      directly combine well-defined NPs synthesized using organic fatty acids in
      nonpolar media with water-soluble polymers, except polyelectrolytes with specific
      functional moieties, because they differ in their hydrophobic/hydrophilic
      properties. We have developed a facile and universal hydrophilic/hydrophobic
      layer-by-layer (LbL) assembly method that enables perfect nanoblending between
      water-soluble polymers and hydrophobic NPs, maintaining their specific
      functionalities. Various hydrophobic NPs stabilized by using oleic acid (OA)
      (e.g., OA-TiO2, OA-Fe3O4, OA-Ag, and OA-Pt NPs) were directly LbL assembled with
      various water-soluble polymers (including biomaterials) containing carboxylic
      acid (-COOH), tertiary ammonium (N+), hydroxyl (-OH), and/or ether (-O-) groups.
      This adsorption behavior is based on the affinities between water-soluble
      polymers with multidentate binding sites and the surfaces of metal or metal oxide
      NPs stabilized by OA ligands. Our approach can be used to fabricate unipolar
      switching nonvolatile memory devices with ON/OFF current ratios greater than
      ~1010 and good memory stability, despite the use of water-soluble polymers.

PMID- 27714185
TI  - Self-propelled autonomous nanomotors meet microfluidics.
AB  - Self-propelled autonomous nano/micromotors are in the forefront of current
      materials science and technology research. These small machines convert chemical
      energy from the environment into propulsion, and they can move autonomously in
      the environment and are capable of chemotaxis or magnetotaxis. They can be used
      for drug delivery, microsurgeries or environmental remediation. It is of immense
      interest from a future biomedical application point of view to understand the
      motion of the nano/micromotors in microfluidic channels. In this minireview, we
      review the progress on the use of nano/micromotors in microfluidic channels and
      lab-on-chip devices.

PMID- 27714186
TI  - A tetra-n-butylammonium iodide mediated reaction of indoles with Bunte salts:
      efficient 3-sulfenylation of indoles under metal-free and oxidant-free
      conditions.
AB  - A highly efficient tetra-n-butylammonium iodide (TBAI) triggered procedure for 3
      sulfenylation of indoles with Bunte salts is demonstrated. This protocol provides
      a simple strategy to prepare 3-alkylthioindoles and 3-arylthioindoles from the
      corresponding indoles under metal-free and oxidant-free conditions.

PMID- 27714187
TI  - Total synthesis of cananginone C and structural revision of debilisone A.
AB  - A short, convergent and general strategy for stereoselective total synthesis of
      biologically active alpha-substituted gamma-hydroxymethyl gamma-lactone based
      natural products cananginone C and debilisone A has been developed. The salient
      features of this synthesis include Cadiot-Chodkiewicz coupling, Evans allylation,
      Sharpless asymmetric dihydroxylation and gamma-lactonization. The originally
      proposed structure of debilisone A has been revised.

PMID- 27714188
TI  - Direct nanopatterning of polymer/silver nanoblocks under low energy electron beam
      irradiation.
AB  - In this communication, we report on the growth, direct writing and nanopatterning
      of polymer/silver nanoblocks under low energy electron beam irradiation using a
      scanning electron microscope. The nanoblocks are produced by placing a droplet of
      an ethylene glycol solution containing silver nitrate and polyvinylpyrrolidone
      diluted in ethanol directly on a hot substrate heated up to 150  degrees C. Upon
      complete evaporation of the droplet, nanospheres, nano- and micro-triangles and
      nanoblocks made of silver-containing polymers, form over the substrate surface.
      Considering the nanoblocks as a model system, we demonstrate that such
      nanostructures are extremely sensitive to the e-beam extracted from the source of
      a scanning electron microscope operating at low acceleration voltages (between 5
      and 7 kV). This sensitivity allows us to efficiently create various nanopatterns
      (e.g. arrays of holes, oblique slits and nanotrenches) in the material under e
      beam irradiation. In addition to the possibility of writing, the nanoblocks
      revealed a self-healing ability allowing them to recover a relatively smooth
      surface after etching. Thanks to these properties, such nanomaterials can be used
      as a support for data writing and erasing on the nanoscale under low energy
      electron beam irradiation.

PMID- 27714189
TI  - Reactions of 1,2-diaza-1,3-butadienes with propargyl alcohol as an approach to
      novel bi-heterocyclic systems.
AB  - Here we describe the reaction of 1,2-diaza-1,3-dienes and propargyl alcohol
      furnishing alpha-(prop-2-yn-1-yloxy)hydrazones that are converted into novel
      alkyl-1-oxa-7,8-diazaspiro[4.4]nona-3,8-dien-6-ones, by means of 2,3-Wittig
      rearrangement under very mild conditions. The same alpha-(prop-2-yn-1
      yloxy)hydrazones, treated with benzyl azides furnish the corresponding alpha
      [(1,2,3-triazol-4-yl)methoxy]hydrazones, via Cu(ii)-catalyzed 1,3-dipolar
      cycloaddition. Their subsequent base-promoted cyclization produces interesting
      pyrazolone-triazole derivatives. The impact of this work can be ascribable to the
      attractiveness of the bi-heterocyclic systems obtained and to the ease of the
      synthetic methodologies proposed.

PMID- 27714190
TI  - Solid-phase synthesis and fluorine-18 radiolabeling of cycloRGDyK.
AB  - Solid-phase peptide synthesis, head-to-tail cyclization, and subsequent
      radiolabeling provided a reproducible, simple, rapid synthetic method to generate
      the cyclic peptide radiotracer cRGDyK([18F]FBA). Herein is reported the first on
      resin cyclization and 18F-radiolabeling of a cyclic peptide (cRGDyK) in an
      overall peptide synthesis yield of 88% (cRGDyK(NH2)) and subsequent radiolabeling
      yield of 14 +/- 2% (decay corrected, n = 4). This approach is generally
      applicable to the development of an automated process for the synthesis of cyclic
      radiolabeled peptides for positron emission tomography (PET).

PMID- 27714191
TI  - Asymmetric total synthesis of (+)-O-methylasparvenone, a rare nitrogen-free
      serotonin 2C receptor antagonist.
AB  - The first enantioselective synthesis of the fungal metabolite (+)-O
      methylasparvenone was achieved in eight steps and 22% overall yield from
      inexpensive 3,4,5-trimethoxybenzaldehyde dimethyl acetal. Key steps include (i)
      early-stage asymmetric alkynylation of an aromatic aldehyde with a propiolate,
      (ii) intramolecular Friedel-Crafts acylation, and (iii) site-selective cleavage
      of an aryl methyl ether.

PMID- 27714192
TI  - Preparation of a Fe3O4-Au-GO nanocomposite for simultaneous treatment of
      oil/water separation and dye decomposition.
AB  - A nanocomposite capable of simultaneously controlling multiple water pollutants
      (soluble organic dye and insoluble chemical solvent) has been obtained. The Au
      and Fe3O4 nanoparticles (NPs) were modified on a graphene oxide (GO) surface via
      light reduction and covalent attachment. The obtained Fe3O4-Au-GO nanocomposite
      has magnetic driving ability and catalytic applications. The nanocomposite can
      form emulsions after wrapping an insoluble and volatile organic solvent inside;
      moreover, the multi-layer graphene shell structure may delay volatilization of
      the solvent, ensuring that the oil droplets are collected efficiently and
      completely by the Fe3O4-Au-GO nanocomposite. At the same time, the Au NPs on the
      surface of the composite can effectively catalyze the decomposition of an organic
      dye in water and the recovery of the nanocomposite catalyst can also be realized
      using an external magnetic field. The simultaneous treatment of non-soluble oil
      (organic solvents) and organic dyes in water can be realized by the Fe3O4-Au-GO
      nanocomposite. Therefore, based on surface modification of GO, one material with
      two types of water pollution treatment functions was realized. This provides a
      new way for the simultaneous treatment of oil separation and dye decomposition,
      and the assembled structure may result in emulsions to give new applications in
      fuel cells and other fields.

PMID- 27714193
TI  - A practical oxidative C-H functionalization of N-carbamoyl tetrahydro-beta
      carbolines with diverse potassium trifluoroborates.
AB  - A practical and mild metal-free oxidative C-H functionalization of N-carbamoyl
      tetrahydro-beta-carbolines has been reported. This reaction has excellent
      functional group tolerance, and exhibits a broad range of potassium
      trifluoroborate components, allowing for the facile C-H functionalization of
      electronically varied N-carbamoyl THCs in high efficiency with excellent
      regioselectivity.

PMID- 27714194
TI  - Organic synthesis reactions on-water at the organic-liquid water interface.
AB  - Organic reactions that occur at the water interface for water-insoluble
      compounds, and reactions in water solution for water soluble compounds, has added
      a powerful dimension to prospects for organic synthesis under more beneficial
      economic and environmental conditions. Many organic molecules are partially
      soluble in water and reactions that appear as heterogeneous mixtures and
      suspensions may involve on-water and in-water reaction modes occurring
      simultaneously. The behavior of water molecules and organic molecules at this
      interface is discussed in the light of reported theoretical and experimental
      studies. The on-water catalytic effect, relative to neat reactions or organic
      solvents, ranges from factors of several hundred times to 1-2 times and it
      depends on the properties of reactant compounds. In some cases when on-water
      reactions produce quantitative yields of water-insoluble products they can reach
      ideal synthetic aspirations.

PMID- 27714195
TI  - A systematic exploration of the effects of flexibility and basicity on sigma
      (sigma) receptor binding in a series of substituted diamines.
AB  - The sigma-1 receptor (S1R) has attracted a great deal of attention as a
      prospective drug target due to its involvement in numerous neurological disorders
      and, more recently, for its therapeutic potential in neuropathic pain. As there
      was no crystal structure of this membrane-bound protein reported until 2016,
      ligand generation was driven by pharmacophore refinements to the general model
      suggested by Glennon and co-workers. The generalised S1R pharmacophore comprises
      a central region where a basic amino group is preferred, flanked by two
      hydrophobic groups. Guided by this pharmacophore, S1R ligands containing
      piperazines, piperazinones, and ethylenediamines have been developed. In the
      current work, we systematically deconstructed the piperazine core of a prototypic
      piperazine S1R ligand (vide infra) developed in our laboratories. Although we did
      not improve the affinity at the S1R compared to the lead, we identified several
      features important for affinity and selectivity. These included at least one
      basic nitrogen atom, conformational flexibility and, for S1R, a secondary or
      tertiary amine group proximal to the anisole. Furthermore, S2R selectivity can be
      tailored with functional group modifications of the N-atom proximal to the
      anisole.

PMID- 27714196
TI  - Monitoring interfacial lectin binding with nanomolar sensitivity using a plasmon
      field effect transistor.
AB  - By immobilizing glycopolymers onto the surface of the recently developed
      plasmonic field effect transistor (FET), the recognition between lectins and
      surface-immobilized glycopolymers can be detected over a wide dynamic range (10
      10 to 10-4 M) in an environment that resembles the glycocalyx. The binding to the
      sensor surface by various lectins was tested, and the selectivities and relative
      binding affinity trends observed in solution were maintained on the sensor
      surface, and the significantly higher avidities are attributed to cluster
      glycoside effects that occur on the surface. The combination of polymer surface
      chemistry and optoelectronic output in this device architecture produces amongst
      the highest reported detection sensitivity for ConA. This work demonstrates the
      benefits that arise from combining emerging device architectures and soft-matter
      systems to create cutting edge nanotechnologies that lend themselves to
      fundamental biological studies and integration into point-of-use diagnostics and
      sensors.

PMID- 27714197
TI  - A diversity-oriented approach to indolocarbazoles via Fischer indolization and
      olefin metathesis: total synthesis of tjipanazole D and I.
AB  - New synthetic strategies to indolocarbazoles have been reported via two-fold
      Fischer indolization under green conditions using l-(+)-tartaric acid and N,N
      dimethyl urea. Starting with cyclohexanone, a bench-top starting material, this
      methodology has been extended to the total synthesis of natural products such as
      tjipanazoles D and I as well as the core structure of asteropusazole and
      racemosin B. Here, atom economical reactions like ring-closing metathesis, enyne
      metathesis, and the Diels-Alder reaction have been used as key steps. Diverse
      strategies demonstrated here are useful in medicinal chemistry and materials
      science to design a library of decorated indoles.

PMID- 27714198
TI  - One-pot N-glycosylation remodeling of IgG with non-natural sialylglycopeptides
      enables glycosite-specific and dual-payload antibody-drug conjugates.
AB  - Chemoenzymatic transglycosylation catalyzed by endo-S mutants is a powerful tool
      for in vitro glycoengineering of therapeutic antibodies. In this paper, we report
      a one-pot chemoenzymatic synthesis of glycoengineered Herceptin using an egg-yolk
      sialylglycopeptide (SGP) substrate. Combining this one-pot strategy with novel
      non-natural SGP derivatives carrying azido or alkyne tags, glycosite-specific
      conjugation was enabled for the development of new antibody-drug conjugates
      (ADCs). The site-specific ADCs and semi-site-specific dual-drug ADCs were
      successfully achieved and characterized with SDS-PAGE, intact antibody or ADC
      mass spectrometry analysis, and PNGase-F digestion analysis. Cancer cell
      cytotoxicity assay revealed that small-molecule drug release of these ADCs relied
      on the cleavable Val-Cit linker fragment embedded in the structure. These results
      represent a new approach for glycosite-specific and dual-drug ADC design and
      rapid synthesis, and also provide the structural requirement for their biologic
      activities.

PMID- 27714199
TI  - Correction: The persistence length of adsorbed dendronized polymers.
AB  - Correction for 'The persistence length of adsorbed dendronized polymers' by Lucie
      Grebikova, et al., Nanoscale, 2016, 8, 13498-13506.

PMID- 27714200
TI  - Design and characterization of red fluorogenic push-pull chromophores holding
      great potential for bioimaging and biosensing.
AB  - Fluorogenic chromophores have been used recently for fluorescence reporting and
      biosensing. Their ability to turn on upon specific interaction with a given
      target has been exploited in particular for the design of fluorogen-based
      reporters enabling biomolecule labeling and imaging. In this paper, we report the
      development and exhaustive characterization of a new family of red fluorogenic
      push-pull chromophores, holding great potential for the development of fluorogen
      based reporters or intracellular fluorogenic markers. The proposed methodology is
      generic and should find general applicability in the discovery of new fluorogenic
      dyes suitable for the design of fluorogen-based reporters and biosensors.

PMID- 27714201
TI  - Synthesis of pyrazolo[1,5-a]quinoxalin-4(5H)-ones via one-pot amidation/N
      arylation reactions under transition metal-free conditions.
AB  - An efficient one-pot transition metal-free procedure for the synthesis of new
      pyrazolo[1,5-a]quinoxalin-4(5H)-ones from easily prepared 1-(2-chlorophenyl-5
      ethylcarboxylate)pyrazoles and various primary alkylamines is described. The key
      steps involved in the synthesis of the new 5,6-fused ring system are the
      formation of an amide intermediate followed by an intramolecular N-arylation
      reaction via nucleophilic aromatic substitution.

PMID- 27714202
TI  - Synthesis, DNA binding affinity and anticancer activity of novel 4H
      benzo[g][1,2,3]triazolo[5,1-c][1,4]oxazocines.
AB  - A new class of tricyclic heterocycles 4H-benzo[g][1,2,3]triazolo[5,1
      c][1,4]oxazocines was synthesized through a Knoevenagel condensation/azide-alkyne
      cycloaddition reaction cascade in one-pot operation. These eight membered ring
      containing heterocycles exhibited moderately high anticancer activity against
      four cancer cell lines; human cervix cancer cell line (HeLa), human prostate
      cancer cell line (DU145), human breast cancer cell line (MCF-7) and human breast
      adenocarcinoma epithelial cell line (MDA-MB-231). Our results indicate that these
      compounds have a weak cytotoxic effect on normal human mammary epithelial cell
      line (MCF-10A). Cell cycle and apoptosis assay indicate that they inhibit the
      cell cycle at the G2/M phase and induce apoptosis. Through the RED100 assay, it
      is evident that they have potential to inhibit pBR 322 plasmid DNA cleavage by
      BamH1. UV-visible, fluorescence titration and viscosity studies suggested that
      these compounds possess DNA binding affinity.

PMID- 27714203
TI  - Hydro-actuation of hybrid carbon nanotube yarn muscles.
AB  - Hybrid hydro-responsive actuators are developed by infiltrating carbon nanotube
      yarns using poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate). These
      actuators demonstrate impressive rotation and contraction in response to water
      due to volumetric expansion of the helical arrangement of carbon nanotubes. The
      total torsional stroke is 3720 revolutions per m and the simultaneously generated
      contractive strain reaches 24% at a paddle-to-yarn mass ratio of 350. The
      contraction output can furthermore be significantly enhanced by constraining the
      rotational motion and it reaches 68% with an applied stress of 1 MPa.
      Additionally, hybrid yarns exhibit an approximately linear response to humidity
      changes and show extra capability of electrical actuation, which, combined with
      the excellent hydro-actuation performance, endow them with great potential for a
      variety of applications including artificial muscles, hydro-driven generators,
      moisture switches and microfluidic mixers.

PMID- 27714204
TI  - Recent advances in the synthesis and application of fluorescent alpha-amino
      acids.
AB  - Fluorescence spectroscopy has become a powerful technique for probing a range of
      complex biological processes including enzyme mechanisms and protein-protein
      interactions. While the application of this technique uses a number of
      strategies, many of these rely on the use of fluorescent alpha-amino acids. This
      review highlights the recent synthetic methods developed for the incorporation of
      highly conjugated chromophores into the side-chain of alpha-amino acids and the
      application of these compounds as probes for imaging in medicine and biology. In
      particular, the design and synthesis of alpha-amino acids bearing coumarin,
      flavone and polyaromatic derived chromophores is described.

PMID- 27714205
TI  - Carboxyl radical-assisted 1,5-aryl migration through Smiles rearrangement.
AB  - We report herein, a silver(i)-catalyzed Smiles rearrangement of 2-aryloxy- or 2
      (arylthio)benzoic acids to provide aryl-2-hydroxybenzoate or aryl-2
      mercaptobenzoate dimer, respectively, through 1,5-aryl migration from oxygen or
      sulfur to carboxylate oxygen. Mechanistically, the aryl ether moiety undergoes an
      intramolecular ipso attack by the carboxyl radical followed by a C-O or C-S bond
      cleavage. Aryl-2-mercaptobenzoates undergo oxidative dimerization through a thiol
      moiety in situ.

PMID- 27714206
TI  - Pure white-light emitting ultrasmall organic-inorganic hybrid perovskite
      nanoclusters.
AB  - Organic-inorganic hybrid perovskites, direct band-gap semiconductors, have shown
      tremendous promise for optoelectronic device fabrication. We report the first
      colloidal synthetic approach to prepare ultrasmall (~1.5 nm diameter), white
      light emitting, organic-inorganic hybrid perovskite nanoclusters. The nearly pure
      white-light emitting ultrasmall nanoclusters were obtained by selectively
      manipulating the surface chemistry (passivating ligands and surface trap-states)
      and controlled substitution of halide ions. The nanoclusters displayed a
      combination of band-edge and broadband photoluminescence properties, covering a
      major part of the visible region of the solar spectrum with unprecedentedly large
      quantum yields of ~12% and photoluminescence lifetime of ~20 ns. The intrinsic
      white-light emission of perovskite nanoclusters makes them ideal and low cost
      hybrid nanomaterials for solid-state lighting applications.

PMID- 27714207
TI  - Synthesis of rotaxanes and catenanes using an imine clipping reaction.
AB  - Supramolecular chemistry and self-assembly provide a valuable chance to
      understand the complicated topological structures on a molecular level. Two types
      of classical mechanically interlocked molecules, rotaxanes and catenanes, possess
      non-covalent mechanical bonds and have attracted more attention not only in
      supramolecular chemistry but also in the fields of materials science,
      nanotechnology and bioscience. In the past decades, the template-directed
      clipping reaction based on imine chemistry has become one of the most efficient
      methods for the construction of functionalized rotaxanes and catenanes. In this
      review, we outlined the main progress of rotaxanes and catenanes using the
      template-directed clipping approach of imine chemistry. The review contains the
      novel topological structures of rotaxanes and catenanes, functions and
      applications.

PMID- 27714208
TI  - Synthesis and complexing properties of cyclic benzylopeptoids - a new family of
      extended macrocyclic peptoids.
AB  - An efficient protocol for the solid-phase synthesis of six members of a new class
      of extended macrocyclic peptoids (based on ortho-, meta- and para-N
      (methoxyethyl)aminomethyl phenylacetyl units) is described. Theoretical (DFT) and
      experimental (NMR) studies on the free and Na+-complexed cyclic trimers (3-5) and
      tetramers (6-8) demonstrate that annulation of the rigidified peptoids can
      generate new hosts with the ability to sequestrate one or two sodium cations with
      the affinities and stoichiometries defined by the macrocycle morphology. Ion
      transport studies have been also performed in order to better appreciate the
      factors promoting transmembrane cation translocation.

PMID- 27714210
TI  - WO3-x sensitized TiO2 spheres with full-spectrum-driven photocatalytic activities
      from UV to near infrared.
AB  - To make full use of solar energy for photocatalytic reactions, in this work, we
      developed full-spectrum-responsive photocatalysts with noteworthy photocatalytic
      activities under either UV, visible or even near infrared irradiation for the
      photodegradation of methylene blue. The core-shell structure of TiO2@WO3-x is
      designed from the consideration of combining the full-spectrum photo-absorption
      properties of WO3-x with the excellent semiconductor properties of TiO2. As
      expected, the WO3-x sensitized TiO2 sphere gives rise to a prominently strong
      optical absorption in the whole region of 300-2500 nm and thus displays desired
      photocatalytic properties for the full utilization of all solar energy,
      especially in the unexploited NIR part, which accounts for most of the sunlight.
      Encouraged by the above exciting photocatalytic outcome, we then go further to
      propose a plausible mechanism for interpreting the NIR-driven photocatalytic
      properties, which is based on the hypothesis of low-valent W5+ site induced free
      electrons and evidence-based ESR results.

PMID- 27714209
TI  - Bifunctional aryloxyphosphoramidate prodrugs of 2'-C-Me-uridine: synthesis and
      anti-HCV activity.
AB  - In an attempt to identify novel nucleoside phosphoramidate analogues for
      improving the anti-HCV activity of 2'-C-Me-uridine, we have synthesized for the
      first time a series of l-glutamic acid, l-serine, l-threonine and l-tyrosine
      containing aryloxyphosphoramidate prodrugs of 2'-C-Me-uridine. Evaluation of
      their activity against HCV revealed that they displayed very potent anti-HCV
      activity, with EC50 values that are in the same range as of Sofosbuvir.

PMID- 27714212
TI  - Synthesis of quinolines and naphthyridines via catalytic retro-aldol reaction of
      beta-hydroxyketones with ortho-aminobenzaldehydes or nicotinaldehydes.
AB  - A Cu(i)-catalyzed retro-aldol reaction of beta-hydroxyketones with ortho
      aminobenzaldehydes and nicotinaldehydes is reported that produces a range of
      quinolines and naphthyridines with high efficiency and selectivity. This reaction
      uses beta-hydroxyketones as a regiospecific ketone-protected enolate source via
      copper-catalyzed retro-aldol Calpha-Cbeta bond cleavage. The in situ generated
      copper enolate undergoes kinetically favorable cyclization with ortho-amino aryl
      aldehydes to produce quinolines and naphthyridines in a chemo- and regioselective
      manner. The mild and weakly basic reaction conditions also suppress possible side
      reactions of benzaldehydes under strongly basic conditions, resulting in improved
      reaction yields.

PMID- 27714211
TI  - A ThDP-dependent enzymatic carboligation reaction involved in Neocarazostatin A
      tricyclic carbazole formation.
AB  - Although the biosynthetic pathway of Neocarazostatin A (1) has been identified,
      the detailed enzymatic reactions underlying the assembly of the carbazole ring
      still remain largely unknown. We demonstrate here that NzsH, a putative thiamine
      diphosphate dependent enzyme, can catalyze an acyloin coupling reaction between
      indole-3-pyruvate and pyruvate to generate a beta-ketoacid intermediate. Our
      findings thus shed light on further characterization of the unusual biosynthetic
      pathway of the bacterial tricyclic carbazole alkaloids.

PMID- 27714213
TI  - The evolution of a stereoselective synthesis of the C1-C16 fragment of
      bryostatins.
AB  - The development of a synthesis of the C1-C16 fragment of bryostatins in which the
      key step is a stereoselective oxy-Michael reaction used to assemble the cis-2,6
      disubstituted tetrahydropyran with the exocyclic alkene already installed, is
      described. Following early work using Stille reactions to prepare precursors for
      oxy-Michael reactions, a more efficient route was devised based on a
      ketophosphonate-aldehyde condensation to prepare the key dienone. Synthesis of
      the aldehyde required for the ketophosphonate condensation involved the highly
      stereoselective addition of a diorganocuprate derived from allylmagnesium bromide
      and copper(i) iodide to the methyl 5-hydroxyhex-2-ynoate prepared by ring-opening
      of a protected glycidol using lithiated methyl propiolate. Ester reduction,
      selective alcohol protection and oxidative cleavage of the terminal double bond
      gave the required aldehyde. The ketophosphonate was prepared in 13 steps from (R)
      pantolactone using a synthesis based on a chelation controlled aldol condensation
      and an anti-selective reduction of a 3-hydroxyketone. Following the
      ketophosphonate-aldehyde reaction, selective deprotection followed by treatment
      with base effected the oxy-Michael reaction that gave the cis-2,6-disubstituted
      tetrahydropyran via thermodynamic control. Subsequent functional group
      manipulation led to the synthesis of a hydroxy ester that corresponded to the C1
      C16 fragment of the bryostatins in 23 steps from (R)-pantolactone. The synthesis
      was repeated using slightly different protecting groups for a study of a ring
      closing metathesis approach to the bryostatins.

PMID- 27714214
TI  - Stereospecific prenylation of tryptophan by a cyanobacterial post-translational
      modification enzyme.
AB  - Prenylation is a key post-translational reaction to increase the structural
      diversity and bioactivity of peptides and proteins. Until now, only one post
      translational modification enzyme, ComQ, has been identified to mediate the
      prenylation of a tryptophan residue in ribosomally synthesized peptides. Here, we
      report the in vitro characterization of KgpF, a novel prenyltransferase which
      transfers dimethylallyl moieties to tryptophan residues during kawaguchipeptin A
      biosynthesis. The stereospecific prenylation by KgpF was determined by a
      combination of in vitro dimethylallylation of Fmoc-tryptophan by KgpF and
      chemical synthesis of dimethylallylated Fmoc-tryptophan diastereomers. KgpF
      modified the tryptophan derivative with a dimethylallyl group at the 3 position
      of its indole ring, resulting in the formation of a tricyclic structure with the
      same scaffold as prenylation by ComQ, but with the opposite stereochemistry.

PMID- 27714215
TI  - Synthesis of trifluoromethylthiolated pyridinones through the copper-mediated
      trifluoromethylthiolation of iodopyridinones.
AB  - An operationally simple method for the copper-mediated trifluoromethylthiolation
      of iodopyridinones employing (bpy)CuSCF3 (1; bpy = 2,2'-bipyridine) as a
      trifluoromethylthiolating reagent is presented. Various types of iodopyridinones
      are applicable and the trifluoromethylthiolated pyridinones are obtained in
      moderate to excellent yields. This method tolerates a variety of protecting
      groups on the nitrogen atom of pyridinones. In addition, scalability of the
      reaction is demonstrated.

PMID- 27714216
TI  - Ethionamide biomimetic activation and an unprecedented mechanism for its
      conversion into active and non-active metabolites.
AB  - Ethionamide (ETH), a second-line anti-tubercular drug that is regaining a lot of
      interest due to the increasing cases of drug-resistant tuberculosis, is a pro
      drug that requires an enzymatic activation step to become active and to exert its
      therapeutic effect. The enzyme responsible for ETH bioactivation in Mycobacterium
      tuberculosis is a monooxygenase (EthA) that uses flavin adenine dinucleotide
      (FAD) as a cofactor and is NADPH- and O2-dependant to exert its catalytic
      activity. In this work, we investigated the activation of ETH by various oxygen
      donor oxidants and the first biomimetic ETH activation methods were developed
      (KHSO5, H2O2, and m-CPBA). These simple oxidative systems, in the presence of ETH
      and NAD+, allowed the production of short-lived radical species and the first non
      enzymatic formation of active and non-active ETH metabolites. The intermediates
      and the final compounds of the activation pathway were well characterized. Based
      on these results, we postulated a consistent mechanism for ETH activation, not
      involving sulfinic acid as a precursor of the iminoyl radical, as proposed so
      far, but putting forward a novel reactivity for the S-oxide ethionamide
      intermediate. We proposed that ETH is first oxidized into S-oxide ethionamide,
      which then behaves as a "ketene-like" compound via a formal [2 + 2] cycloaddition
      reaction with peroxide to give a dioxetane intermediate. This unstable 4-membered
      intermediate in equilibrium with its open tautomeric form decomposes through
      different pathways, which would explain the formation of the iminoyl radical and
      also that of different metabolites observed for ETH oxidation, including the ETH
      NAD active adduct. The elucidation of this unprecedented ETH activation mechanism
      was supported by the application of isotopic labelling experiments.

PMID- 27714217
TI  - Design, synthesis and biological activities of new brassinosteroid analogues with
      a phenyl group in the side chain.
AB  - We have prepared and studied a series of new brassinosteroid derivatives with a p
      substituted phenyl group in the side chain. To obtain the best comparison between
      molecular docking and biological activities both types of brassinosteroids were
      synthesized; 6-ketones, 10 examples, and B-lactones, 8 examples. The phenyl group
      was introduced into the steroid skeleton by Horner-Wadsworth-Emmons. The docking
      studies were carried out using AutoDock Vina 1.05. Plant biological activities
      were established using different brassinosteroid bioassays in comparison with
      natural brassinosteroids. Differences in the production of the plant hormone
      ethylene were also observed in etiolated pea seedlings after treatment with new
      brassinosteroids. The most active compounds were lactone 8f and 6-oxo derivatives
      8c and 9c, their biological activities were comparable or even better than
      naturally occurring brassinolide. Finally the cytotoxicity of the new derivatives
      was studied using human normal and cancer cell lines.

PMID- 27714218
TI  - A facile approach for the synthesis of C13-C24 fragments of maltepolides A, C and
      D.
AB  - A linear, chiron approach for the synthesis of C13-C24 fragments of cytostatic
      maltepolides A, C and D consisting of a tetrahydrofuran subunit and a chiral
      alkenyl/alkyl substituent is achieved from (+)-diethyl l-tartrate. The other
      chiral stereocenters were generated by employing key reactions such as Crimmins
      aldol, alkynylation and CeCl3.7H2O mediated Luche reduction reactions.

PMID- 27714219
TI  - A red fluorophore comprising a borinate-containing xanthene analogue as a polyol
      sensor.
AB  - A xanthene derivative containing a borinate moiety emitted red fluorescence with
      a high quantum yield. The interaction between the borinate and a sugar molecule
      induced a fluorescence change based on the change in the HOMO-LUMO gap. The
      response was pH-resistant in a wide range. In addition, catechol quenched through
      photoinduced electron transfer. The red fluorescence and polyol binding ability
      of dyes will pave the way for new biological applications of chemical sensors.

PMID- 27714220
TI  - The effect of photocatalyst excited state lifetime on the rate of photoredox
      catalysis.
AB  - Four different iridium(iii) polypyridyl complexes with varying excited state
      lifetimes are used as photocatalysts to study the effect of excited state
      lifetime on the rate of a prototypical photoredox-catalyzed reaction, the
      trifluoromethylation of quinoline. An improved mechanistic understanding of the
      photocatalysis is achieved, enabling guided optimization of reaction conditions
      and elucidating the role of the photocatalyst excited state lifetime on the rate
      of photocatalysis.

PMID- 27714221
TI  - DBN hexafluorophosphate salts as convenient sulfonylating and phosphonylating
      agents.
AB  - Air-stable N-sulfonyl and N-phosphonyl DBN hexafluorophosphate salts have been
      synthesised under mild conditions as sulfonylating and phosphonylating agents.
      These salts are highly efficient in the sulfonylation and phosphonylation of a
      range of N- and O-nucleophiles to generate sulfonamides, sulfonate esters,
      phosphoramidates and phosphonate esters in good yields.

PMID- 27714222
TI  - Structure and biocatalytic scope of thermophilic flavin-dependent halogenase and
      flavin reductase enzymes.
AB  - Flavin-dependent halogenase (Fl-Hal) enzymes have been shown to halogenate a
      range of synthetic as well as natural aromatic compounds. The exquisite
      regioselectively of Fl-Hal enzymes can provide halogenated building blocks which
      are inaccessible using standard halogenation chemistries. Consequently, Fl-Hal
      are potentially useful biocatalysts for the chemoenzymatic synthesis of
      pharmaceuticals and other valuable products, which are derived from haloaromatic
      precursors. However, the application of Fl-Hal enzymes, in vitro, has been
      hampered by their poor catalytic activity and lack of stability. To overcome
      these issues, we identified a thermophilic tryptophan halogenase (Th-Hal), which
      has significantly improved catalytic activity and stability, compared with other
      Fl-Hal characterised to date. When used in combination with a thermostable flavin
      reductase, Th-Hal can efficiently halogenate a number of aromatic substrates. X
      ray crystal structures of Th-Hal, and the reductase partner (Th-Fre), provide
      insights into the factors that contribute to enzyme stability, which could guide
      the discovery and engineering of more robust and productive halogenase
      biocatalysts.

PMID- 27714223
TI  - De novo protecting-group-free total synthesis of (+)-muricadienin, (+)
      ancepsenolide and (+)-3-hexadecyl-5-methylfuran-2(5H)-one.
AB  - A de novo protecting-group-free total synthesis of (+)-muricadienin, (+)
      ancepsenolide and (+)-3-hexadecyl-5-methylfuran-2(5H)-one has been achieved. Ring
      closing-metathesis has been the key step in the synthesis. In (+)-muricadienin
      synthesis, a long chain alkyl group has been installed by an sp-sp3 Sonogashira
      type reaction followed by a cis-selective Lindlar reduction. The total synthesis
      is achieved in 7 steps and in excellent 43.5% overall yield. Similarly, (+)
      ancepsenolide and (+)-3-hexadecyl-5-methylfuran-2(5H)-one synthesis is completed
      in 5 steps each and in 48 and 68% overall yields, respectively.

PMID- 27714224
TI  - Modular access to vicinally functionalized allylic (thio)morpholinonates and
      piperidinonates by substrate-controlled annulation of 1,3-azadienes with
      hexacyclic anhydrides.
AB  - A modular substrate-controlled hexannulation of inherently promiscuous 1,3
      azadienes with hexacyclic anhydrides, which affords versatile vicinally
      functionalized allylic lactams, in high yields, regio- and stereoselectivities is
      described.

PMID- 27714225
TI  - Acoustically propelled nanoshells.
AB  - Herein we report a new design for acoustic nanoswimmers, making use of a
      nanoshell geometry that was synthesized using a sphere template process. Such
      shell-shaped nanomotors display highly efficient acoustic propulsion on the
      nanoscale by converting energy from the ambient acoustic field into motion. The
      propulsion mechanism of the nanoshell motors relies on acoustic streaming stress
      over the asymmetric surface to produce the driving force for motion. The shell
      shaped nanomotors offer a high surface area to volume ratio, allow for efficient
      scalability and provide higher cargo towing capacity (in comparison to
      acoustically propelled nanowires). Furthermore, a detailed study of the
      parameters relevant to propulsion performance, including the material density,
      size and shape of the motors, reveals that the nanoshell motors exhibit a
      different propulsion behavior from that predicted by recent theoretical and
      experimental models for acoustically propelled nanomotors. Such findings indicate
      that further studies are needed to predict the behavior of acoustic nanomotors
      with different geometry designs. Practical applications of the new nanoshell
      motors, including "on-the-move" capture and the transport of multiple cargoes and
      internalization and movement inside live MCF-7 cancer cells, are demonstrated.
      These capabilities hold considerable promise for designing fuel-free nanoswimmers
      capable of performing complex tasks for diverse biomedical applications.

PMID- 27714226
TI  - Base-mediated one-pot synthesis of 1,2,4-oxadiazoles from nitriles, aldehydes and
      hydroxylamine hydrochloride without addition of extra oxidant.
AB  - A simple base-mediated one-pot synthesis of 3,5-disubstituted 1,2,4-oxadiazoles
      from nitriles, aldehydes and hydroxylamine hydrochloride has been developed, in
      which the aldehydes act as both substrates and oxidants. The reactions include
      three sequential procedures: base-promoted intermolecular addition of
      hydroxylamine to nitrile to lead to amidoxime, treatment of the amidoxime with an
      aldehyde to form 4,5-dihydro-1,2,4-oxadiazole, and oxidization of the 4,5-dihydro
      1,2,4-oxadiazole by using another aldehyde to afford 1,2,4-oxadiazole. This
      method represents a direct and simple protocol for the synthesis of 3,5
      disubstituted 1,2,4-oxadiazoles.

PMID- 27714227
TI  - Racemic and enantioselective metal-catalyzed synthesis of SF5-containing
      diarylmethanols.
AB  - The racemic and enantioselective metal-catalyzed addition of arylboronic acids to
      4- and 3-(pentafluorosulfur)benzaldehydes is reported. The racemic synthesis was
      accomplished using a Pd-based system and a wide range of arylboronic acids could
      be used, resulting in yields of 42 to 98% of the corresponding SF5-containing
      diarylmethanols. A ruthenium-based system, along with (R,R)-Me-BIPAM as the
      chiral ligand, was investigated and optimized for the enantioselective version.
      In this case, while the chiral SF5-containing diarylmethanols were generally
      obtained in good yields (up to 94%) and enantioselectivities (up to 98% ee),
      limitations were also observed. For instance, 4-(pentafluorosulfur)benzaldehyde
      generally provided slightly better yields than 3-(pentafluorosulfur)benzaldehyde.
      In addition, lower yields and enantioselectivities were observed when using
      either 4- and 3-substituted arylboronic acids bearing electron-withdrawing (e.g.,
      CO2Et, NO2, CF3) or 2-substituted arylboronic acids (regardless of the nature of
      the substituent). Overall, the SF5-containing diarylmethanols described herein
      represent novel and potentially useful fluorinated building blocks for the
      synthesis of biologically active compounds.

PMID- 27714228
TI  - Titania-coated gold nanorods with expanded photocatalytic response. Enzyme-like
      glucose oxidation under near-infrared illumination.
AB  - Gold nanorods coated with a uniform titanium dioxide nanoshell have been prepared
      and used as glucose-oxidase surrogates. Remarkably, this core-shell
      photocatalytic nanostructure has been able to induce complete oxidation of
      glucose at near room temperature (32-34  degrees C) in a wide range of pH values
      with the aid of a near-infrared (NIR) irradiation source. In contrast, the
      uncoated gold nanorods exhibit negligible photo-oxidation response under
      identical experimental conditions thereby proving the photoactivity of the
      titania shell towards glucose oxidation. The process takes place via in situ
      photo-generation of singlet oxygen or hydroxyl radicals as reactive oxidative
      species (ROS). This underlines the role played by the core nanorods as plasmonic
      light harvesters in the NIR range and constitutes the first example of a NIR
      activated enzyme-like catalyst.

PMID- 27714229
TI  - Bioactive norditerpenoids and neolignans from the roots of salvia miltiorrhiza.
AB  - Two new norditerpenoids, miltiolactones A and B (1a, 1b); seven new neolignans,
      miltiolignanolides A-G (2a, 2b and 3a, 3b and 4a, 4b, and 5) were obtained from
      the root extract of Salvia miltiorrhiza. Using HPLC separation with a chiral
      column, compounds 1-4 were found to exist as four pairs of enantiomers. Compounds
      2-5 are novel neolignans with a dibenzocycloheptatriene ring system, which form
      an unprecedented 6/7/6 carbon skeleton. The structures were established via
      extensive spectroscopic analysis, and experimental and calculated electronic
      circular dichroism (ECD) spectra, and compound 1 was also elucidated by X-ray
      diffraction experiments. Compounds 2a and 2b significantly increased the
      viability of H9c2 cells from H2O2-induced cell death, and 3a showed significant
      antioxidant activity in an ABTS assay. In addition, compounds 2a, 2b and 3a, 3b
      display moderate inhibitory effects on nitric oxide (NO) production in LPS
      induced microglial cells.

PMID- 27714230
TI  - Direct alkylthio-functionalization of unsubstituted perylenediimides.
AB  - Herein, we report a simple fluoride-mediated reaction for the direct mono- and
      dialkylthio-functionalization of unsubstituted perylenediimides (PDIs) under very
      mild conditions. The aromatic substitution reaction offers the possibility to
      introduce primary, secondary and, even, tertiary alkanethiols either on the 1- or
      on the 1,6-bay positions of unsubstituted PDIs. 1,6-DialkylthioPDIs show that
      absorption and fluorescence spectra shifted to the red when compared with the
      unsubstituted PDI, with Stokes shifts around 70-80 nm.

PMID- 27714231
TI  - Visible light-promoted synthesis of 4-(sulfonylmethyl)isoquinoline-1,3(2H,4H)
      diones via a tandem radical cyclization and sulfonylation reaction.
AB  - Heterocyclic derivatives 4-(sulfonylmethyl)isoquinoline-1,3(2H,4H)-diones were
      synthesized via a visible-light-promoted reaction of N-alkyl-N-methacryloyl
      benzamides with sulfonyl chlorides catalyzed by fac-Ir(ppy)3 at room temperature.
      With various substituents on the substrates, the reaction proceeded smoothly to
      give the corresponding products in good to excellent yields. The products could
      be converted into 3-hydroxy-4-(sulfonylmethyl)-3,4-dihydroisoquinolin-1(2H)-one
      derivatives by the reduction of NaBH4.

PMID- 27714232
TI  - Carbocation-pi interaction: evaluation of the stabilization by phenylalanine of a
      biochemical carbocation intermediate.
AB  - Computational analyses, using primarily density functional theory, have been used
      to determine the stabilization associated with the carbocation-pi interaction of
      a biochemical carbocation intermediate binding to a phenylalanine residue in an
      enzyme active site. Studies of complexation between t-butyl cation and
      ethylbenzene, and of a model of a carbocation intermediate with a phenylalanine
      in the active site of geranyl diphosphate C-methyl transferase, have afforded the
      first quantitative evaluation of the stabilization that can be provided to a
      carbocation by an aromatic residue in an enzymatic reaction. Describing the
      hydrophobic surrounding medium using a dielectric constant between epsilon = 2
      and epsilon = 4, the calculated carbocation-pi stabilization energy lies in the
      range of 10-7.5 kcal mol-1.

PMID- 27714233
TI  - C2-Symmetric pyrrolidine-derived squaramides as recyclable organocatalysts for
      asymmetric Michael reactions.
AB  - Novel C2-symmetric N,N'-bis-[(pyrrolidin-2-yl)methyl-squaramide] TFA salts
      bearing (R,R)- or (S,S)-1,2-di(pyridin-2-yl)ethane spacer groups were synthesized
      and applied, in combination with TEA, as efficient organocatalysts for asymmetric
      reactions between cyclohexanone derivatives and beta-nitrostyrenes to afford the
      corresponding Michael adducts in high yields with good to excellent
      enantioselectivity. The catalytic procedure is readily scalable and recyclable
      over four times without a negative impact on the selectivity of the reaction.
      Some of the prepared compounds are valuable precursors to useful bioactive
      molecules.

PMID- 27714234
TI  - Double heteroannulation of S,N-acetals: a facile access to quinolone derivatives.
AB  - A rapid construction of quinolone fused heterocycles from single S,N-acetal
      precursors via double heteroannulation is described. The base, radical and metal
      mediated reactions can control the C-N, C-S and C-O bond formations of the S,N
      acetal with high chemoselectivity.

PMID- 27714235
TI  - Dynamical behavior of boron clusters.
AB  - Several of the lowest energy structures of small and medium sized boron clusters
      are two-dimensional systems made up of a pair of concentric rings. In some cases,
      the barriers to the rotation of one of those rings relative to the other are
      remarkably low. We find that a combination of electronic and geometrical factors,
      including apparently the relative sizes and symmetries of the inner and outer
      rings, are decisive for the diminished barriers to in-plane rotation in these two
      dimensional clusters. A sufficiently large outer ring is important; for instance,
      expansion of the outer ring by a single atom may reduce the barrier
      significantly. A crucial factor for an apparent rotation is that the sigma
      skeleton of the individual rings remains essentially intact during the rotation.
      Finally, the transition state for the rotation of the inner ring comprises the
      transformation of a square into a diamond, which may be linked to a mechanism
      suggested decades ago for the isomerization of carboranes and boranes.

PMID- 27714236
TI  - Introduction of a tailor made anion receptor into the side chain of small
      peptides allows fine-tuning the thermodynamic signature of peptide-DNA binding.
AB  - The binding between peptides and DNA is often driven by entropic forces. We
      demonstrate herein a new approach to shift the thermodynamic profile of
      peptide/DNA binding from entropy to enthalpy driven. This eventually leads to
      higher compacted DNA aggregates which are important for gene transfection.

PMID- 27714237
TI  - Three-step synthesis of l-ido-1-deoxynojirimycin derivatives by reductive
      amination in water, "borrowing hydrogen" under neat conditions and deprotection.
AB  - In this communication, we describe a three-step synthesis of l-ido-1
      deoxynojirimycin derivatives starting from readily available 2,3,4,6-tetra-O
      benzyl-d-glucopyranose via Ir-catalyzed reductive amination in water, "borrowing
      hydrogen" under neat conditions, and Pd-catalyzed debenzylation.

PMID- 27714238
TI  - Evolution of specific 3'-5'-linkages in RNA in pre-biotic soup: a new hypothesis.
AB  - This article reviews the different possibilities towards progression of the
      formation of DNA/RNA in the chemical world, before life, in enzyme-free
      conditions. The advent of deoxyribo- and ribopentose-sugars, nucleosides,
      nucleotides and oligonucleotides in the prebiotic soup is briefly discussed.
      Further, the formation of early single stranded oligomers, base-pairing
      possibilities and information transfer based on the stability parameters of the
      derived duplexes is reviewed. Each theory has its own merits and demerits which
      we have elaborated upon. Lastly, using clues from this literature, a possible
      explanation for the specific 3'-5'-linkages in RNA is proposed.

PMID- 27714239
TI  - Tetrazolone as an acid bioisostere: application to marketed drugs containing a
      carboxylic acid.
AB  - Matched molecular pair analysis was used to evaluate the ability of a tetrazolone
      group to act as a bioisostere of a carboxylic acid. Compound 7, a tetrazolone of
      the anti-hypertensive drug, telmisartan 6, was shown to be a potent AT1
      antagonist (Kb = 0.14 nM), with activity comparable to telmisartan itself (Kb =
      0.44 nM). Additionally, compound 9, a tetrazolone congener of the marketed anti
      cancer agent, bexarotene 8, was shown to be an agonist at the retinoid X receptor
      alpha (EC50 = 64 nM). Compounds containing a tetrazolone group showed similar
      microsomal stability and plasma protein binding to marketed acid counterparts,
      while also reducing the value for clog P. Furthermore, compound 7 displayed an
      improved rat pharmacokinetic profile cf. telmisartan 6. Taken together, the
      results demonstrate that a tetrazolone group may serve as a bioisostere for a
      carboxylic acid.

PMID- 27714240
TI  - Substitution dependent stereoselective construction of bicyclic lactones and its
      application to the total synthesis of pyranopyran, tetraketide and polyrhacitide
      A.
AB  - A novel bicyclization strategy has been developed for the stereoselective
      synthesis of bicyclic lactones, i.e. 7-aryl or alkyl-2,6-dioxabicyclo[3.3.1]nonan
      3-ones through a domino cyclization of (R)-3-hydroxyhex-5-enoic acid with an
      aldehyde in the presence of 10 mol% trimethylsilyltriflate under mild conditions.
      The salient features of this methodology are high yields, excellent selectivity,
      low catalyst loading and faster reaction times. This method has been successfully
      applied to the total synthesis of pyranopyran, tetraketide and polyrhacitide A.

PMID- 27714241
TI  - The chemistry of ynol and thioynol ethers.
AB  - Alkynyl ethers and alkynyl thioethers ('ynol ethers' and 'thioynol ethers') are
      appealing building-blocks in synthetic chemistry due to their ease of
      manipulation and predictable reactivity. Until recently however, their potential
      has remained underexploited due to difficulties in preparation and isolation.
      Although recent advances in synthetic chemistry have highlighted various
      applications for ynol ethers, the equivalent thioynol examples have been rather
      less exploited despite a unique and fascinating reactivity profile. Although
      superficially the chemistry of alkynyl ethers and their sulfide counterparts are
      similar, close examination of their chemistry reveals important differences which
      can be exploited by the synthetic chemist. This review will examine the
      preparation of both classes of compound and examine their reactivity to highlight
      their powerful synthetic applications. Particular focus will be made of thiynol
      ethers whose chemistry exhibits some fascinating differences compared to their
      oxygen counterparts and have immense untapped potential for synthetic chemistry.

PMID- 27714242
TI  - Tin powder-promoted one-pot synthesis of 3-spiro-fused or 3,3'-disubstituted 2
      oxindoles.
AB  - A convenient and efficient method for the constructions of 3-spirooxindole
      derivatives or 3,3'-disubstituted oxindoles has been developed from one-pot
      reactions of isatins, hydrazides or aromatic amines, 2-(bromomethyl)acrylic ester
      and tin powder in the presence of a catalytic amount of Bronsted or Lewis acid.
      The method avoids the use of toxic stannanes and allows easy operation. It is
      also proved that hydrazides are more favorable for intramolecular cyclization
      than amines.

PMID- 27714243
TI  - Inhibitory properties of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) derivatives
      acting on glycogen metabolising enzymes.
AB  - Glycogen synthase (GS) and glycogen phosphorylase (GP) are the key enzymes that
      control, respectively, the synthesis and degradation of glycogen, a multi
      branched glucose polymer that serves as a form of energy storage in bacteria,
      fungi and animals. An abnormal glycogen metabolism is associated with several
      human diseases. Thus, GS and GP constitute adequate pharmacological targets to
      modulate cellular glycogen levels by means of their selective inhibition. The
      compound 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) is a known potent inhibitor of
      GP. We studied the inhibitory effect of DAB, its enantiomer LAB, and 29 DAB
      derivatives on the activity of rat muscle glycogen phosphorylase (RMGP) and E.
      coli glycogen synthase (EcGS). The isoform 4 of sucrose synthase (SuSy4) from
      Solanum tuberosum L. was also included in the study for comparative purposes.
      Although these three enzymes possess highly conserved catalytic site
      architectures, the DAB derivatives analysed showed extremely diverse inhibitory
      potential. Subtle changes in the positions of crucial residues in their active
      sites are sufficient to discriminate among the structural differences of the
      tested inhibitors. For the two Leloir-type enzymes, EcGS and SuSy4, which use
      sugar nucleotides as donors, the inhibitory potency of the compounds analysed was
      synergistically enhanced by more than three orders of magnitude in the presence
      of ADP and UDP, respectively. Our results are consistent with a model in which
      these compounds bind to the subsite in the active centre of the enzymes that is
      normally occupied by the glucosyl residue which is transferred between donor and
      acceptor substrates. The ability to selectively inhibit the catalytic activity of
      the key enzymes of the glycogen metabolism may represent a new approach for the
      treatment of disorders of the glycogen metabolism.

PMID- 27714244
TI  - Can the analyte-triggered asymmetric autocatalytic Soai reaction serve as a
      universal analytical tool for measuring enantiopurity and assigning absolute
      configuration?
AB  - An investigation is reported on the use of the autocatalytic enantioselective
      Soai reaction, known to be influenced by the presence of a wide variety of chiral
      materials, as a generic tool for measuring the enantiopurity and absolute
      configuration of any substance. Good generality for the reaction across a small
      group of test analytes was observed, consistent with literature reports
      suggesting a diversity of compound types that can influence the stereochemical
      outcome of this reaction. Some trends in the absolute sense of stereochemical
      enrichment were noted, suggesting the possible utility of the approach for
      assigning absolute configuration to unknown compounds, by analogy to closely
      related species with known outcomes. Considerable variation was observed in the
      triggering strength of different enantiopure materials, an undesirable
      characteristic when dealing with mixtures containing minor impurities with strong
      triggering strength in the presence of major components with weak triggering
      strength. A strong tendency of the reaction toward an 'all or none' type of
      behavior makes the reaction most sensitive for detecting enantioenrichment close
      to zero. Consequently, the ability to discern modest from excellent
      enantioselectivity was relatively poor. While these properties limit the ability
      to obtain precise enantiopurity measurements in a simple single addition
      experiment, prospects may exist for more complex experimental setups that may
      potentially offer improved performance.

PMID- 27714245
TI  - Groove modification of siRNA duplexes to elucidate siRNA-protein interactions
      using 7-bromo-7-deazaadenosine and 3-bromo-3-deazaadenosine as chemical probes.
AB  - Elucidation of dynamic interactions between RNA and proteins is essential for
      understanding the biological processes regulated by RNA, such as RNA interference
      (RNAi). In this study, the logical chemical probes, comprising 7-bromo-7
      deazaadenosine (Br7C7A) and 3-bromo-3-deazaadenosine (Br3C3A), to investigate
      small interfering RNA (siRNA)-RNAi related protein interactions, were developed.
      The bromo substituents of Br7C7A and Br3C3A are expected to be located in the
      major and the minor grooves, respectively, and to act as a steric hindrance in
      each groove when these chemical probes are incorporated into siRNAs. A
      comprehensive investigation using siRNAs containing these chemical probes
      revealed that (i) Br3C3A(s) at the 5'-end of the passenger strand enhanced their
      RNAi activity, and (ii) the direction of RISC assembly is determined by the
      interaction between Argonaute2, which is the main component of RISC, and siRNA in
      the minor groove near the 5'-end of the passenger strand. Utilization of these
      chemical probes enables the investigation of the dynamic interactions between RNA
      and proteins.

PMID- 27714246
TI  - Copper-catalyzed oxidative cyclization of vinyl azides with benzylic Csp3-H bonds
      for the synthesis of substituted phenanthridines.
AB  - A copper-catalyzed oxidative cyclization of vinyl azides with benzylic Csp3-H
      bonds via a tandem dual C-H functionalization process has been developed. This
      procedure allows access to substituted phenanthridines containing a variety of
      functional groups. In addition to benzyl hydrocarbons, other substrates
      containing unactivated Csp3-H bonds, such as ethers and alkanes could also be
      applied successfully to this transformation.

PMID- 27714247
TI  - Strain-promoted azide-alkyne cycloaddition for protein-protein coupling in the
      formation of a bis-hemoglobin as a copper-free oxygen carrier.
AB  - Conventional chemical approaches to protein-protein coupling present challenges
      due to the intrinsic competition between the desired interactions of reagents
      with groups of the protein as well as reactions with water. Biorthogonal Cu(i)
      catalyzed azide-alkyne cycloaddition (CuAAC)-processes provide a basis to direct
      reactivity without functional group interference. However, the requirement for
      Cu(i) in CuAAC leads to complications that result from the metal ion's
      interactions with the protein. In principle, a similar but metal-free alternative
      approach to coupling could employ the reaction of an alkyne that is strained in
      combination with an azide (strain-promoted azide-alkyne cycloaddition, SPAAC).
      The method is exemplified by the combination of a cyclooctyne derivative of
      hemoglobin with an azide-modified hemoglobin. The bis-hemoglobin tetramer that is
      produced has properties consistent with those sought for use as a hemoglobin
      based oxygen carrier (HBOC).

PMID- 27714248
TI  - Peptide-substituted phthalocyanine photosensitizers: design, synthesis,
      photophysicochemical and photobiological studies.
AB  - A series of phthalocyanine-peptide-quencher conjugates (6-9) were synthesized as
      photosensitizers for photodynamic therapy in cancer treatment. The photophysical,
      photochemical and photobiological properties of these activatable molecular
      beacons were also investigated in this study. For this purpose, the fluorescence,
      singlet oxygen and photodegradation quantum yields and fluorescence lifetime
      values of the compounds were determined in DMSO solutions. The phototoxicity and
      cytotoxicity of the systems were studied against the cervical cancer cell line
      named HeLa for an evaluation of their suitability for photodynamic therapy. The
      results showed that a maximum of 80% of HeLa cells were killed following light
      irradiation with photodynamic efficiency. All of the results showed that the
      novel activatable molecular beacons could be suitable candidates for cancer
      treatment via PDT technique.

PMID- 27714249
TI  - Proton-coupled electron transfer in the reduction of carbonyls using SmI2-H2O:
      implications for the reductive coupling of acyl-type ketyl radicals with SmI2
      H2O.
AB  - Samarium diiodide-water (SmI2-H2O) reagents have emerged as some of the most
      practical systems enabling reduction and reductive cyclizations of ketyl
      radicals. Recently, this reaction manifold has been extended to acyl-type
      radicals generated from cyclic polar carboxylic acid derivatives. However, the
      relationship between the fundamental electron- and proton-transfer steps in the
      generation of ketyl-type radicals with SmI2-H2O remains unclear. An intriguing
      scenario involves an initial proton-coupled electron transfer (PCET) mechanism
      from SmI2-H2O to the carbonyl group. Herein, we calculate with high accuracy bond
      dissociation free energies (BDFE) for the O-H bond in ketyl radicals in 14 cyclic
      and acyclic ketone, ester, imide and amide substrates and in anthracene relevant
      to reductions with SmI2-H2O and quantitatively assess the feasibility of
      concerted PCET in the reduction of carbonyl groups using SmI2-H2O. Reduction
      potentials of all substrates have been calculated. The data argue against
      concerted PCET from SmI2-H2O to carbonyl substrates.

PMID- 27714250
TI  - Screening of Neu5Acalpha(2-6)gal isomer preferences of siglecs with a sialic acid
      microarray.
AB  - Sialic acids (Sias) are important terminal sugars on cell surfaces involved in a
      wide range of protein-carbohydrate interactions. Hence, agents modulating sias
      mediated protein interactions are promising inhibitors or vaccine candidates.
      Here, we report the synthesis of Neu5Acalpha(2-6)Gal structural analogs and their
      binding to a series of siglecs. The results showed distinct binding patterns with
      conserved siglecs (hCD22 and mCD22) compared to rapid evolving siglecs (Siglecs 
      3 & -10).

PMID- 27714251
TI  - Developments toward the synthesis and application of 3-hydroxyindanones.
AB  - 3-Hydroxyindanone is an important scaffold in many natural products, biologically
      active compounds, and functional materials. This review provides a comprehensive
      overview of the construction of 3-hydroxyindanone derivatives and their
      applications towards pharmaceutically promising drug candidates. The total
      synthesis of the complex natural products containing this simple core is
      discussed. The highlights of the literature from 1948 to 2015 are comprised.

PMID- 27714252
TI  - A protecting group-free synthesis of (-)-hortonones A-C from the Inhoffen-Lythgoe
      diol.
AB  - A synthesis of hortonones A-C has been accomplished from vitamin D2via the
      Inhoffen-Lythgoe diol without the use of protective groups. Key steps in the
      syntheses include a TMS-diazomethane mediated regioselective homologation of the
      cyclohexanone ring to a cycloheptanone moiety and a sodium naphthalenide-mediated
      allylic alcohol transposition. It has been found that the absolute configuration
      of the natural hortonones is opposite that of the synthetic material prepared
      from vitamin D2.

PMID- 27714253
TI  - A halogen bond does not dictate the conformational preferences of cis-1,3
      disubstituted cyclohexanes.
AB  - Halogen bonds are defined as interactions between halogens and a Lewis base in
      which the halogen (X) acts as the electrophilic species, and is typically
      explained by the presence of a sigma-hole at the end of the C-X bond. Despite the
      important role of the halogen bond in intermolecularly interacting species, e.g.
      in acid-base reactions, enzyme inhibition and the supramolecular architecture,
      this interaction was not found to control the conformational equilibrium of some
      small model molecules, namely cis-1,3-disubstituted cyclohexanes. In addition,
      the attraction between the electrophilic (sigma-hole) and nucleophilic regions is
      used to explain that the halogen bond was weaker than that in the species with
      parallel C-X bonds. Therefore, intramolecular halogen bonds should be used with
      caution to explain the conformational stability of organic compounds.

PMID- 27714254
TI  - Rapid assembly of spirocycles with phenol-derived biaryls with alkynes using an
      oxidative C-H activation/dearomatization strategy.
AB  - The development of new methods for the rapid assembly of spirocyclic frameworks
      with high molecular complexity is always of great importance for organic
      syntheses. In this perspective, we endeavour to cover the recent achievements
      from our group in the construction of synthetically valuable
      spirocyclohexadienones from easily accessible phenol-derived biaryls using a
      transition-metal-catalyzed C-H activation/dearomatization strategy. The key
      feature of these cooperative reactions is the simultaneous C-H bond activation
      and aromaticity disruption, leading to the formation of various spirocyclic
      molecules that are difficult or inaccessible using conventional approaches.

PMID- 27714255
TI  - Total synthesis of diptoindonesin G and its analogues as selective modulators of
      estrogen receptors.
AB  - We have developed a versatile synthetic strategy for the synthesis of the natural
      product diptoindonesin G and its analogues as selective modulators of estrogen
      receptors. The strategy involves a regioselective dehydrative cyclization of
      arylacetals, a regioselective bromination of benzofurans, a sequential cross
      coupling of bromo-benzofurans with aryl boronic acids, and a BBr3-mediated tandem
      cyclization and demethylation. Preliminary biological studies uncovered the
      critical and dispensable phenolic hydroxyl groups in the natural product and also
      revealed unexpected selectivity for isoforms of estrogen receptor.

PMID- 27714256
TI  - Magnesium salt promoted tandem nucleophilic addition-Oppenauer oxidation of
      aldehydes with organozinc reagents.
AB  - A magnesium salt promoted synthesis of ketones via tandem nucleophilic addition
      Oppenauer oxidation of aldehydes using organozinc chemistry was demonstrated.
      Magnesium salts concomitantly generated via magnesium metal mediated organohalide
      zincation exhibit high efficacy for nucleophilic addition of organozinc reagents
      to aromatic aldehydes and thereafter Oppenauer oxidation whereby ketones are
      formed in high to excellent yields.

PMID- 27714258
TI  - Comment on "Formation of polyelectrolyte multilayers: ionic strengths and growth
      regimes" by K. Tang and A. M. Besseling, Soft Matter, 2016, 12, 1032.
AB  - Tang and Besseling recently published a study on the growth of polyelectrolyte
      multilayers formed by poly(diallyl-dimethylammonium chloride), PDADMAC, and the
      sodium salt of poly(4-styrenesulfonate), PSSNa. They described the different
      growth regimes appearing in the (PDADMAC + PSS)n multilayers within a scenario in
      which the appearance of interdiffusion of the polyelectrolyte chains within the
      multilayer architecture plays a central role in the transition between the
      different regimes. However, this account contrasts, without an apparent
      explanation, with previous experimental evidence reported in the literature.

PMID- 27714257
TI  - New synthetic approaches towards analogues of bedaquiline.
AB  - Multi-drug resistant tuberculosis (MDR-TB) is of growing global concern and
      threatens to undermine increasing efforts to control the worldwide spread of
      tuberculosis (TB). Bedaquiline has recently emerged as a new drug developed to
      specifically treat MDR-TB. Despite being highly effective as a result of its
      unique mode of action, bedaquiline has been associated with significant
      toxicities and as such, safety concerns are limiting its clinical use. In order
      to access pharmaceutical agents that exhibit an improved safety profile for the
      treatment of MDR-TB, new synthetic pathways to facilitate the preparation of
      bedaquiline and analogues thereof have been discovered.

PMID- 27714259
TI  - Chemoselective photooxygenations of furans bearing unprotected amines: their use
      in alkaloid synthesis.
AB  - Very recent investigations are described, which have shown how basic and
      unprotected nitrogen functionalities can be included, problem-free, in the furan
      photooxidation step of singlet oxygen-initiated cascade reaction sequences. The
      amine groups do not react with singlet oxygen, but, instead, participate later on
      in the sequences that ultimately yield a diverse range of important alkaloid
      motifs. To illustrate the versatility of this chemistry, six natural products
      were synthesised very rapidly and efficiently. Furthermore, all the new
      technologies operated under green conditions and without the use of a single
      protecting group.

PMID- 27714260
TI  - The excitation intensity dependence of singlet fission dynamics of a rubrene
      microcrystal studied by femtosecond transient microspectroscopy.
AB  - We have investigated the excitation intensity dependence of the singlet fission
      in a crystalline rubrene by means of femtosecond transient absorption
      microspectroscopy. When a rubrene microcrystal was excited to higher energy
      levels than that of the lowest singlet excited (S1) state with a 397 nm
      femtosecond laser pulse, a triplet excited state was formed through two pathways
      of the singlet fission, i.e. the direct fission from higher vibrational levels of
      the S1 state with a time constant of 2.2 ps and the thermally activated fission
      from the S1 state in a few tens of ps. The time constant of the thermally
      activated fission changed from 35 to 17 ps for increasing of the laser fluence
      from 0.65 to 18 mJ cm-2 per pulse, although that of the direct fission was
      constant with the excitation laser intensity. On the other hand, the yield of the
      triplet formation was independent of the intensity. We also examined the
      temperature dependence of the singlet fission and demonstrated the activation
      energy of the thermally activated fission to be 0.21 eV. Based on the
      experimental results, we considered the excitation intensity dependence of the
      singlet fission of the rubrene crystal in terms of the effect of transient local
      heating on a ps time scale after femtosecond laser excitation owing to the
      nonradiative vibrational relaxation from the higher vibrational level to the
      lower one in the S1 state.

PMID- 27714261
TI  - A near-infrared fluorescent probe based on chloroacetate modified
      naphthofluorescein for selectively detecting cysteine/homocysteine and its
      application in living cells.
AB  - We have prepared a near-infrared (NIR) turn-on fluorescent probe (NFC) based on
      chloroacetate modified naphthofluorescein for specific detection of cysteine
      (Cys) and homocysteine (Hcy) over glutathione (GSH) and other amino acids (AAs)
      with the detection limits of 0.30 MUM and 0.42 MUM, respectively. The
      fluorescence intensity of the naphthofluorescein (NF) chromophore is modulated by
      an internal charge transfer (ICT) process. The probe NFC is readily available and
      weakly fluorescent, but of observably enhanced fluorescence after reacting with
      Cys or Hcy. We assumed and then demonstrated that the fluorescence off-on process
      involves a conjugate nucleophilic substitution/cyclization sequence. Furthermore,
      the probe has been successfully applied for detecting the total content of Cys
      and Hcy in human plasma and imaging in living cells with low toxicity.

PMID- 27714262
TI  - Synthesis of furostanol glycosides: discovery of a potent alpha-glucosidase
      inhibitor.
AB  - A convenient approach to the synthesis of furostanol glycosides has been
      developed with the features of both highly efficient incorporation of a 26-O-beta
      d-glucopyranosyl unit and ready formation of hemiketal ring E. The total
      syntheses of seven furostanol saponins including funlioside B, lilioglycoside,
      protobioside I, protodioscin, pallidifloside I, coreajaponins A and parisaponin I
      are efficiently achieved using an easily available 16beta-acetoxy-22-oxo-26
      hydroxy-cholestanic derivative as a powerful building block. The alpha
      glucosidase inhibitory activity of the synthesized saponins is also evaluated,
      which reveals that funlioside B is a highly potential lead for developing alpha
      glucosidase inhibitors.

PMID- 27714263
TI  - Formation and flow behavior of micellar membranes in a T-shaped microchannel.
AB  - Understanding the formation and instability behavior of membranes is of
      fundamental interest and practical relevance to various biotechnological
      applications and self-assembly systems. Surfactant micellar membranes serve as a
      simple model system when surfactant molecules self-assemble into micellar
      structures under flow, but observing such process in real time is a major
      challenge due to limitations in spatiotemporal resolutions. We use a simple T
      shaped microchannel to capture the formation and flow behavior of an ionic
      surfactant micro-micellar-membrane (MUMM) when an aqueous stream of organic salt
      sodium salicylate (NaSal) meets a stream of cationic surfactant
      cetyltrimethylammonium bromide (CTAB). The MUMM is shown to grow and become
      unstable depending on the flow rate, as characterized using micro-particle image
      velocimetry, fluorescence microscopy, flow birefringence, and bulk rheometry. We
      propose a simple model that accounts for the flow, elasticity and inertia of the
      MUMM to analyze its flow behavior. Our experimental protocol can be easily
      replicated in conventional laboratories without the need of utilizing
      sophisticated equipment such as synchrotron small angle X-ray scattering and
      micro-electronics circuits. Our combined experimental and modeling results can be
      extrapolated to provide new insights to study the flow behavior and thermodynamic
      phases of lipid membranes, membrane proteins, and biological membranes.

PMID- 27714264
TI  - Topical treatment of green tea polyphenols emulsified in carboxymethyl cellulose
      protects against acute ultraviolet light B-induced photodamage in hairless mice.
AB  - Ultraviolet (UV) radiation causes skin injury and inflammation resulting in
      impaired immune response and increased risk of skin cancer. It has been shown
      that green tea polyphenols (GTPs) enhanced intracellular antioxidant defense and
      promoted the downregulation of proapoptotic genes, and they could be used to
      protect against the damage induced by UV irradiation. However, the high
      instability and poor bioavailability of GTPs impose restrictions on their
      potential pharmacological use. Here we show that carboxymethyl cellulose sodium
      (CMC-Na) had a stabilizing effect on GTPs under aqueous conditions and topical
      application of GTPs (emulsified in CMC-Na) had a strong photoprotective effect
      against acute UVB induced photodamage in uncovered (Uncv) hairless mice skin.
      After 8 h of incubation at 50  degrees C with CMC-Na, a percentage i.e. 93% of
      GTPs was preserved, while in the absence of CMC-Na, a percentage of only 61% was
      preserved. Topical treatment of emulsified GTPs effectively inhibited acute UVB
      induced infiltration of inflammatory cells, increase of skin thickness, oxidative
      stress such as depletion of antioxidant enzymes and lipid oxidation, and induced
      nuclear accumulation of Nrf2 in the mice skin. We also discovered the ability of
      GTPs to simultaneously trigger accumulation of nuclear Nrf2 and export of nuclear
      Bach1. Altogether, our findings reinforced the putative application of GTPs in
      the prevention/minimization of the deleterious effects of UV on the skin.

PMID- 27714265
TI  - Synthesis of HIV-1 capsid protein assembly inhibitor (CAP-1) and its analogues
      based on a biomass approach.
AB  - A biomass-derived platform chemical was utilized to access a demanded
      pharmaceutical substance with anti-HIV activity (HIV, human immunodeficiency
      virus) and a variety of structural analogues. Step economy in the synthesis of
      the drug core (single stage from cellulose) is studied including flexible
      variability of four structural units. The first synthesis and X-ray structure of
      the inhibitor of HIV-1 capsid protein assembly (CAP-1) is described.

PMID- 27714266
TI  - Rhodium(iii)-catalyzed ortho-alkenylation using a cyclic N-phosphoryl ketimine as
      the directing group.
AB  - A novel cyclic N-phosphoryl ketimine structure can efficiently react with olefins
      as useful directing groups to construct a myriad of phosphate scaffolds via
      rhodium(iii)-catalyzed ortho-alkenylation. This method provides a probability
      that the coupling products could be used as a building block to access more
      complex organic phosphorus compounds.

PMID- 27714267
TI  - An expeditious synthesis of the ascomycete metabolite rigidiusculamide B.
AB  - The ascomycete metabolite rigidiusculamide B was synthesised in six steps and 22%
      overall yield. The key steps were a Li2Te-triggered Dittmer-type Dieckmann
      cyclisation of an N-(alpha-haloacyl)tyrosine ester to give a 4-O-silyl tetramate,
      followed by its fluoride-assisted desilylation-oxidation with oxygen. The product
      3-hydroxy-pyrrolidine-2,4-dione was obtained as a 6 : 1 mixture of separable
      diastereoisomers.

PMID- 27714268
TI  - Biphenyl urea derivatives as selective CYP1B1 inhibitors.
AB  - Highly selective CYP1B1 inhibitors have potential in the treatment of hormone
      induced breast and prostate cancers. Mimicry of potent and selective CYP1B1
      inhibitors, alpha-naphthoflavone and stilbenes, revealed that two sets of
      hydrophobic clusters suitably linked via a polar linker could be implanted into a
      new scaffold 'biphenyl ureas' to create potentially a new class of CYP1B1
      inhibitors. A series of sixteen biphenyl ureas were synthesized and screened for
      CYP1B1 and CYP1A1 inhibition in SacchrosomesTM, yeast-derived recombinant
      microsomal enzymes. The most active human CYP1B1 inhibitors were further studied
      for their selectivity against human CYP1A1, CYP1A2, CYP3A4 and CYP2D6 enzymes.
      The meta-chloro-substituted biphenyl urea 5h was the most potent inhibitor of
      CYP1B1 with IC50 value of 5 nM. It displayed excellent selectivity over CYP1A1,
      CYP1A2, CYP3A4 and CYP2D6 (IC50 >10 MUM in the four CYP assays, indicating >2000
      fold selectivity). Similarly, two methoxy-substituted biphenyl ureas 5d and 5e
      also displayed potent and selective inhibition of CYP1B1 with IC50 values of 69
      and 58 nM, respectively, showing >62 and >98-fold selectivity over CYP1A1,
      CYP1A2, CYP3A4 and CYP2D6 enzymes. In order to probe if the relatively insoluble
      biphenyl ureas were cell permeable and if they could at all be used for future
      cellular studies, their CYP1B1 inhibition was investigated in live recombinant
      human and yeast cells. Compound 5d displayed the most potent inhibition with
      IC50s of 20 nM and 235 nM, respectively, in the two cell-based assays. The most
      potent and selective CYP1B1 inhibitor (compound 5h) from Sacchrosomes, also
      displayed potent inhibition in live cell assays. Molecular modeling was performed
      to understand the trends in potency and selectivity observed in the panel of five
      CYP isoenzymes used for the in vitro studies.

PMID- 27714269
TI  - Phosphorylated cyclopropanes in the synthesis of alpha-alkylidene-gamma
      butyrolactones: total synthesis of (+/-)-savinin, (+/-)-gadain and (+/-)
      peperomin E.
AB  - Phosphorylated cyclopropanes, generated via the Rh(ii)-catalysed intramolecular
      cyclopropanation of alpha-(diethoxyphosphoryl)acetates, have been found to be
      useful precursors in the synthesis of alpha-alkylidene-gamma-butyrolactones.
      These cyclopropyl intermediates undergo regioselective reductive ring-opening and
      subsequent Horner-Wadsworth-Emmons olefination to complete the synthesis. Total
      syntheses of (+/-)-savinin and (+/-)-gadain, as well as the first total synthesis
      of (+/-)-peperomin E, are all described using this method.

PMID- 27714270
TI  - Synthesis of novel styryl-N-isopropyl-9H-carbazoles for designing trans
      conjugated regular silicon hybrid materials.
AB  - An efficient synthesis and characterization of several new, conjugated styryl
      carbazole compounds functionalized by monovinylsilanes in a stereocontrolled
      approach is presented. All N-organic derivatives were successfully examined in
      silylative coupling in the presence of ruthenium-hydride complexes 4 and 5.
      Furthermore, a novel class of vinylene-arylene linear oligomeric materials with
      1,4-bis(dimethylvinylsilyl)naphthalene in the main chain was produced. Both
      reactions proceed very effectively, stereo- and regioselectively, allowing one to
      obtain E-isomer derivatives with high isolation yields.

PMID- 27714271
TI  - Radiation damage to single stranded oligonucleotide trimers labelled with 5
      iodopyrimidines.
AB  - The radiolysis of deoxygenated aqueous solution containing trimeric
      oligonucleotides labelled with iodinated pyrimidines and Tris-HCl as the hydroxyl
      radical scavenger leads to electron attachment to the halogenated bases that
      mainly results in single strand breaks. The iodinated trimers are 2-fold more
      sensitive to solvated electrons than the brominated oligonucleotides, which is
      explained by the barrier-free dissociation of the iodinated base anions. The
      present study fills the literature gap concerning the chemistry triggered by
      ionizing radiation in the iodinated pyrimidines incorporated into DNA.

PMID- 27714272
TI  - Iron(iii) chloride hexahydrate-promoted selective hydroxylation and chlorination
      of benzyl ketone derivatives for the construction of hetero-quaternary scaffolds.
AB  - A novel and tunable alpha-hydroxylation/alpha-chlorination of benzyl ketone
      derivatives has been developed for the construction of hetero-quaternary carbon
      centers by iron(iii) chloride hexahydrate mediated selective transformations
      through the application of different oxidants, especially the crystal water in
      the catalyst as an OH source is firstly reported in this hydroxylation.

PMID- 27714273
TI  - Computation-guided improved one-pot synthesis of macrocyclic cation-binding
      aromatic pyridone pentamers.
AB  - By using polar DMF to relax the H-bonded rigid backbone and to lower the
      energetic penalty associated with the sterically-crowded environment, the yields
      for BOP-mediated one-pot synthesis of pentameric macrocycles can be improved from
      10-25% as obtained in CH2Cl2 to 13-47% when 15% DMF in CH2Cl2 was used as the
      reaction medium.

PMID- 27714274
TI  - Enantioselective synthesis of alpha,alpha-disubstituted alpha-amino acids via
      direct catalytic asymmetric addition of acetonitrile to alpha-iminoesters.
AB  - alpha,alpha-Disubstituted alpha-amino acids have attracted increasing interest
      due to their potential utility as building blocks of unnatural peptides. Herein
      we document an enantioselective entry to this class of compounds through the
      direct catalytic addition of acetonitrile to alpha-iminoesters bearing an N
      thiophosphinoyl group. Chiral N-heterocyclic carbene complexes of [Ir(cod)(OMe)]2
      catalytically rendered the catalytic generation of alpha-cyanocarbanions from
      acetonitrile in combination with Barton's base, followed by enantioselective
      addition to the imino carbonyl group, delivering a variety of enantioenriched
      alpha-cyanomethylated alpha,alpha-disubstituted alpha-amino acid derivatives.

PMID- 27714275
TI  - Photocatalytic degradation of ibuprofen using TiO2 sensitized by Ru(ii) polyaza
      complexes.
AB  - In this work, modification of TiO2 was carried out by incorporation of two novel
      Ru(ii) polyaza complexes. The N1-(2-aminobenzyliden)-N2,N2-bis(2-(2
      aminobenzyliden)aminoethyl)ethane-1,2-diaminoruthenium(ii) and N1,N2-bis(2
      aminobenziliden)ethane-1,2-diaminoruthenium(ii) complexes were synthesized via
      metal-ligand direct reaction. The complexes were characterized by UV-Vis, FTIR
      and fluorescence spectroscopy, and the chemical composition was obtained from
      elemental analysis by the combustion method; additionally, the sensitized TiO2
      catalysts were also characterized by XRD, SEM and diffuse reflectance techniques.
      The photocatalytic activity of the prepared catalysts was tested in a batch
      reactor under visible radiation for the degradation of ibuprofen in aqueous
      solution. The evolution of the drug degradation process was evaluated by high
      performance liquid chromatography (HPLC), while the mineralization percentage was
      monitored by the determination of total organic carbon (TOC). The results
      indicated that the incorporation of these complexes improves the activation of
      TiO2 under visible light, increasing the degradation and mineralization
      percentage of ibuprofen up to 35% compared to the unmodified material, thereby
      making it suitable for application in heterogeneous photocatalysis of the said
      pharmaceutical in aqueous media using visible light as the energy source.

PMID- 27714276
TI  - Temperature-boosted photocatalytic H2 production and charge transfer kinetics on
      TiO2 under UV and visible light.
AB  - This study investigates the effect of reaction temperature (298-353 K) on
      photocatalytic H2 production in bare and platinized TiO2 (Pt/TiO2) suspensions
      containing various organic hole scavengers (EDTA, methanol, and formic acid)
      under UV (lambda > 320 nm) and visible light (lambda > 420 nm for ligand-to-metal
      charge transfer). H2 production rates are enhanced ~7.8- and ~2.5-fold in TiO2
      and Pt/TiO2 suspensions, respectively, with EDTA under UV by simply elevating the
      reaction temperature from 298 K to 323 K (DeltaT = 25  degrees C). Such a
      temperature-boosted increase in H2 production is always observed, regardless of
      the TiO2 crystalline structure (anatase, rutile, and an anatase/rutile mixture),
      type of hole scavenger, and irradiation wavelength range. It is estimated that
      approximately 90% of incident photons are utilized in H2 production, for which
      the activation energy is 25.5 kJ mol-1. Detailed photoelectrochemical analyses
      show the positive relationship between reaction temperature and photocurrent
      generation, with charge carrier mobility and interfacial charge transfer
      improving at higher temperatures. Other possible factors, such as H2 solubility
      and mass transport, play a limited role.

PMID- 27714277
TI  - Spontaneous exfoliation of a drying gel.
AB  - Wet starch cracks when it dries inhomogeneously, while hot glass cracks when it
      cools non-uniformly. In both cases, differential shrinkage induced by
      drying/cooling from the surface causes superficial cracks to grow perpendicular
      to the surface in different patterns. In contrast with these observations of bulk
      cracking in brittle materials, when a soft and homogeneously swollen polymer gel
      dries, differential strains lead to the peeling of a thin layer that
      spontaneously tears away from the bulk. Continued drying leads to the process
      repeating itself, forming a peeled-layered structure. The emergent thickness of
      the exfoliated layer is a function of both the geometry of the original gel and
      the physical parameters associated with the drying rate and external temperature.
      We characterize the experimental conditions under which layer peeling can arise,
      and use simulations to corroborate these observations. Finally, a minimal theory
      explains the scaling of the peel thickness, consistent with our experiments.

PMID- 27714278
TI  - Radical-radical cross coupling reactions of photo-excited fluorenones.
AB  - Radical-radical cross coupling reactions of photoexcited 9-fluorenones have been
      accomplished for the first time, leading to the synthesis of 9-alkyl,
      pyrollidinyl and spiro-THF derivatives of 9-fluorenones. The method also reveals,
      for the first time, the behaviour of ketyl radicals in decarboxyaltive alkylation
      and ring expansion reactions.

PMID- 27714279
TI  - Lipid structure influences the ability of glucose monocorynomycolate to signal
      through Mincle.
AB  - Mincle (macrophage-inducible C-type lectin) is a C-type lectin receptor that
      provides the capacity for immune sensing of a range of pathogen- and commensal
      derived glycolipids. Mincle can recognize mycolic and/or corynomycolic acid
      esters of trehalose, glycerol and glucose from mycobacteria and corynebacteria.
      While simple straight-chain long fatty acids (e.g. behenic acid) can substitute
      for mycolic acid on trehalose and glycerol and maintain robust signalling through
      Mincle, glucose monobehenate has been reported to be much less active than
      glucose monocorynomycolate (GMCM). We report the preparation of a range of
      analogues of GMCM to explore structural requirements in the lipid chain for
      signalling through Mincle. GMCM analogues bearing simple straight chain or
      branched fatty acid esters provided only weak signalling through human and mouse
      Mincle. A GMCM variant with a truncated (pentyl) alpha-chain provided attenuated
      signalling, whereas an analogue with an extended (tricosyl; C23) alpha-chain
      signalled as potently as GMCM. This work suggests that Mincle has the ability to
      survey mycolate-derived glycolipids from actinomycetes, distinguishing non
      pathogenic (e.g. Rhodococcus spp.) and pathogenic (e.g. Mycobacterium
      tuberculosis) species on the basis of alpha-chain length. Finally, an alpha
      phenyldodecyl analogue of GMCM possessed similar potency to GMCM and was only
      slightly less potent than trehalose dimycolate (cord factor), showing that large
      functional groups may be tolerated in the alpha-chain.

PMID- 27714280
TI  - Recent progress towards gold-catalyzed synthesis of N-containing tricyclic
      compounds based on ynamides.
AB  - N-Containing tricyclic compounds, especially the tricyclic N-heterocycles, are
      important structural motifs that possess significant potential in organic
      chemistry for their momentous applications in natural and man-made bioactive
      molecules. Gold catalysis, which exhibits specific catalytic properties in terms
      of both high reactivity and selectivity for various organic transformations, has
      proven to be a powerful tool for the straightforward synthesis of cyclic
      compounds, especially the polycyclic molecules. Currently, several approaches
      towards polycycle synthesis have been developed via gold-catalyzed
      transformations of readily available ynamides. In this review, we will focus on
      the recent advances in the gold-catalyzed construction of N-containing tricycles
      based on ynamides by highlighting their specificity and applicability, and the
      mechanistic rationale is presented where possible.

PMID- 27714281
TI  - Palladium meets copper: one-pot tandem synthesis of pyrido fused heterocycles via
      Sonogashira conjoined electrophilic cyclization.
AB  - An efficient step-economical tandem approach for the direct synthesis of pyrido
      fused indole, quinoline, benzofuran and benzothiophene derivatives using a
      bimetallic Pd/Cu catalytic system has been described. The three component
      reaction of o-halo aldehydes, alkynes and tert-butylamine leads to the synthesis
      of biologically active polyheterocycles. The present strategy involves the dual
      role of tert-butylamine and copper(i) in Sonogashira coupling followed by
      electrophilic cyclization through imine formation. The chemistry has been
      validated by X-ray crystallographic studies.

PMID- 27714282
TI  - A fluorescent acrylamide-type monomer bearing an environment-sensitive
      methoxybenzocoumarin structure for the development of functional polymeric
      sensors.
AB  - A new fluorescent acrylamide-type monomer bearing a hydrogen bonding- and
      polarity-sensitive benzocoumarin fluorophore was synthesized. The absorption
      spectra, fluorescence spectra, and fluorescence lifetime of a model compound were
      measured in ten solvents with different hydrogen-bonding abilities and polarities
      to investigate the sensitivity of the fluorophore to the surrounding environment.
      These spectroscopic studies demonstrated that the fluorophore emits stronger
      fluorescence in more protic, polar environments. A fluorescent polymeric
      thermometer was prepared from N-isopropylacrylamide and the new fluorescent
      monomer, and it showed good functionality in aqueous solution (e.g., high
      sensitivity to temperature changes and high chemical stability), indicating the
      applicability of the herein developed fluorescent monomer for use in functional
      sensors.

PMID- 27714283
TI  - Synthesis and biological evaluation of triazole based uracil derivatives as novel
      DPP-4 inhibitors.
AB  - A series of triazole based uracil derivatives were designed and synthesized as
      novel DPP-4 inhibitors. Compound A01 was identified as a lead compound for SAR
      studies focused on the structural modification at the S2' subsite of DPP-4. The
      novel analogues A02-A25 were obtained by modifying the substituents at the phenyl
      group, and B01-B09, by introducing the carbonyl group. On screening in DPP-4,
      compounds B03, B04 and B08 showed a significant improvement in DPP-4 inhibitory
      activities compared to compound A01 and showed comparable activities to the
      marketed DPP-4 inhibitor, alogliptin. Docking studies revealed new favorable
      binding modes of designed compounds in the S2' subsite and proved that structural
      modifications in the S2' subsite were an effective option to increase the
      inhibition of DPP-4. In vitro DPP-8 and DPP-9 tests indicated that all compounds
      showed excellent selectivity against DPP-8 and DPP-9. Further in vivo evaluation
      showed that compound B04 could significantly improve oral glucose tolerance in
      ICR mice and dose-dependently reduced glucose levels in type 2 diabetic C57BL/6
      mice. These data suggest that compound B04 could be a promising DPP-4 inhibitor
      for future treatment of T2DM.

PMID- 27714284
TI  - I2-Mediated 2H-indazole synthesis via halogen-bond-assisted benzyl C-H
      functionalization.
AB  - I2-Mediated benzyl C-H functionalization has been developed for the synthesis of
      2H-indazoles, which features high efficiency, simple conditions and no need for
      metals. Mechanistic experiments and DFT calculations have revealed halogen bond
      assistance and a radical chain process for this reaction. The azo group and the
      bound iodine cooperate in the hydrogen abstraction step, which circumvents the
      thermodynamic disfavor of direct hydrogen abstraction by a simple iodine radical.

PMID- 27714285
TI  - Regioselective synthesis of functionalized dihydroisoquinolines from o
      alkynylarylaldimines via the Reformatsky reaction.
AB  - A novel approach for the synthesis of functionalized 1,2-dihydroisoquinolines
      from o-alkynylarylaldimines via the Reformatsky reaction without the aid of an
      external Lewis acid has been described. The chemistry involves the dual role of
      the Reformatsky reagent which has been generated in situ in the reaction. We
      propose that one molecule of the Reformatsky reagent is being utilised for the
      activation of alkynes, whereas the second molecule acts as a nucleophile on the
      iminium carbon. This synthetic pathway has high functional group tolerance, and
      can be utilized on a gram scale. The proposed mechanistic pathway is well
      supported by the control experiments. The 1,2-dihydroisoquinoline derivatives
      showed up to 90% inhibition of the strand transfer activity of the HIV integrase
      enzyme.

PMID- 27714286
TI  - Generalized drift velocity of a cholesteric texture in a temperature gradient.
AB  - We propose a general method to calculate the drift velocity of cholesteric
      textures subjected to a temperature gradient when the backflow effects are
      negligible. The textures may be Translationally Invariant Configurations (TICs)
      or localized structures such as cholesteric droplets or cholesteric fingers. For
      the TICs and for the droplets, the drift is rotational while for the fingers, the
      drift is translational. We show that for the TICs, the drift is only due to the
      thermomechanical coupling terms of Leslie (classical term) and of Akopyan and
      Zel'dovich (which are additional texture-dependent terms). For the localized
      structures, we show that another mechanism involving the temperature variations
      of the elastic constants and the existence of a transverse temperature gradient
      can lead to a drift which adds to the one due the classical thermomechanical
      effects.

PMID- 27714287
TI  - Chemically reduced graphene oxide-P25-Au nanocomposite materials and their
      photoelectrocatalytic and photocatalytic applications.
AB  - Visible light active photocatalysts consisting of gold nanoparticle (Au NP)
      decorated chemically reduced graphene oxide-P25 nanocomposite materials (CRGO-P25
      Au NCMs) were prepared through a one-pot chemical reduction method. The
      nanocomposite materials were characterized using diffuse reflectance spectroscopy
      (DRS), X-ray diffraction (XRD), high-resolution transmission electron microscopy
      (HRTEM) and electrochemical impedance spectroscopy (EIS) analyses. The
      performances of CRGO-P25-Au NCM modified ITO electrodes were evaluated towards
      the photoelectrochemical oxidation of methanol. The photoelectrode fabricated
      using CRGO-P25-Au NCM exhibited a higher photocurrent of 293 MUA cm-2 compared to
      other control electrodes. The CRGO-P25-Au NCMs were also used for the
      photocatalytic reduction of highly toxic chromium(vi) ions to chromium(iii) ions
      in the presence of oxalic acid as a sacrificial electron donor. The results
      showed that around 75% of the Cr(vi) ions were photocatalytically reduced to
      Cr(iii) ions by the CRGO-P25-Au NCM within the light irradiation time of 1 h. In
      both applications, the enhanced catalytic activity of the CRGO-P25-Au NCM was
      attributed to the improved visible light absorption and the reduced charge
      recombination exerted by the interaction of CRGO and Au NPs with P25 and their
      synergistic effects.

PMID- 27714288
TI  - A general approach to iridoids by applying a new Julia olefination and a tandem
      anion-radical-carbocation crossover reaction.
AB  - A unified, asymmetric approach to the total synthesis of naturally occurring
      iridoids is presented. The synthesis features a recently discovered ortho ->
      alpha transmetalation of alkyl aryl sulfone carbanions, thus enabling Julia
      reactions, by which so far hardly accessible disilylated olefins have been
      obtained. A subsequent tandem alkoxycarbonylation/oxidative radical cyclization
      afforded substituted cyclopentane building blocks with high diastereoselectivity.
      These compounds serve as unique central intermediates for short access to
      dihydronepetalactone, dolicholactone and potentially other iridoids.

PMID- 27714289
TI  - Regioselective copper-catalyzed N(1)-(hetero)arylation of protected histidine.
AB  - We report regioselective N(1)-arylation of protected histidine using copper(i)
      iodide as a catalyst, trans-N,N'-dimethylcyclohexane-1,2-diamine as a ligand and
      readily available aryl iodides as coupling partners under microwave irradiation
      at 130  degrees C for 40 min. The reaction provides rapid access to electron
      donating, electron-withdrawing and bulky group substituted N-arylated histidines
      in high yields, including previously inaccessible N-heteroaryl histidines. These
      N(1)-(hetero)aryl histidines are promising building blocks in peptide-based drug
      design and discovery.

PMID- 27714290
TI  - A toolset of functionalized porphyrins with different linker strategies for
      application in bioconjugation.
AB  - The reaction of amines with pentafluorophenyl-substituted A3B-porphyrins has been
      used to obtain different useful reactive groups for further functionalization
      and/or conjugation of these porphyrins to other substrates or materials.
      Porphyrins with alkenyl, alkynyl, amino, azido, epoxide, hydroxyl, and maleimido
      groups have thus been synthesized. For the first time such functionalized
      porphyrins have been conjugated to hyperbranched polyglycerol (hPG) as a
      biocompatible carrier system for photodynamic therapy (PDT) using the copper(i)
      catalyzed 1,3-dipolar cycloaddition (CuAAC). The photocytotoxicity of selected
      porphyrins as well as of the porphyrin-hPG-conjugates has been assessed in
      cellular assays with human epidermoid carcinoma A-253 and squamous carcinoma CAL
      27 cells. For several biomedical applications a release of the active drug and/or
      fluorescent dye is desired. Therefore, additionally, the synthesis of A3B
      porphyrins with cleavable linker moieties is presented, namely disulfide,
      cleavable in a reductive environment, and acetal linkers whose cleavage is pH
      triggered.

PMID- 27714291
TI  - Morphology control of three-dimensional nanostructures in porous templates using
      lamella-forming block copolymers and solvent vapors.
AB  - The microphase separation behavior of block copolymers confined in cylindrical
      nanopores has been extensively investigated. Recently, the solvent-annealing
      induced nanowetting in templates (SAINT) method has been demonstrated to be a
      versatile approach for the infiltration of block copolymers into the nanopores of
      porous templates. The function of the annealing solvents, however, is still not
      well understood, especially in the morphology control of the fabricated block
      copolymer nanostructures. In this work, we elucidate the function of the
      annealing solvents in the SAINT method using a lamella-forming block copolymer,
      polystyrene-block-polydimethylsiloxane (PS-b-PDMS), and anodic aluminum oxide
      (AAO) templates. By changing the composition of the annealing solvents, different
      morphologies such as the concentric lamellar morphology, the winding cylinder
      morphology, and the irregular hybrid morphology are observed, mainly caused by
      the annealing-solvent-induced volume change. The morphology of the block
      copolymer nanostructures can be further confirmed using an HF solution to remove
      the PDMS domain selectively.

PMID- 27714292
TI  - Torsional stiffness determines aggregate structure in sheared colloidal rod
      suspensions.
AB  - We report the results of simulations of suspensions of sheared rigid rods in the
      presence of strong attractive inter-particle interactions, using dissipative
      particle dynamics for a coarse-grained representation of the suspending fluid. We
      find that the combined effect of the attractive interactions and shear-induced
      alignment generically produces aggregates of aligned bundles when the contact
      points between rods are free to rotate. However, the introduction of substantial
      torsional stiffness to the inter-particle contacts recapitulates the disordered
      aggregates often observed in suspensions of high aspect ratio particles. We show
      that the degree of alignment within the aggregates depends on the strength of the
      torsional stiffness, while the stability of the aggregates and their impact on
      system viscosity depend on the competition between the attractive interaction and
      the shear stresses.

PMID- 27714293
TI  - Enhancing and reducing chirality by opposite circularly-polarized light
      irradiation on crystalline chiral domains consisting of nonchiral photoresponsive
      W-shaped liquid crystal molecules.
AB  - We found possible chirality enhancement and reduction in chiral domains formed by
      photoresponsive W-shaped molecules by irradiation with circularly polarized light
      (CPL). The W-shaped molecules exhibit a unique smectic phase with spontaneously
      segregated chiral domains, although the molecules are nonchiral. The chirality
      control was generated in the crystalline phase, which shows chiral segregation as
      in the upper smectic phase, and the result appeared to be as follows: for a
      certain chiral domain, right-CPL stimuli enhanced the chirality, while left-CPL
      stimuli reduced the chirality, and vice versa for another chiral domain.
      Interestingly, no domain-size change could be observed after CPL irradiation,
      suggesting some changes in the causes of chirality. In this way, the present
      system can recognize the handedness of the applied chiral stimuli. In other
      words, the present material can be used as a sensitive chiral-stimuli-recognizing
      material and should find invaluable applications, including in chiroptical
      switches, sensors, and memories as well as in chiral recognition.

PMID- 27714294
TI  - Stretching liquid bridges with moving contact lines: comparison of liquid
      transfer predictions and experiments.
AB  - Transfer of liquid from one surface to another plays a key role in printing
      processes. During liquid transfer, a liquid bridge is formed and then undergoes
      significant extensional motion while its contact lines are free to move on the
      bounding solid surfaces. In this work, we develop one-dimensional (1D) slender
      jet and two-dimensional (2D) axisymmetric models of this phenomenon and compare
      the resulting predictions with previously published experimental data. For very
      low capillary numbers (Ca) (quasi-static stretching), predictions from both
      models of the amount of liquid transferred agree well with the experimental data,
      provided that the difference in receding contact angles (|Deltathetar|) between
      the two surfaces is sufficiently large. Notably, the amount of liquid transferred
      is primarily governed by the overall bridge shape and is not significantly
      influenced by contact-line motion toward the end of bridge stretching. For O(1)
      values of Ca, the models predict that each surface receives half the liquid, in
      agreement with experimental observations. For intermediate values of Ca (and very
      low values of Ca when |Deltathetar| is small enough), predictions from each model
      can deviate substantially from the experimental data, which we speculate is due
      to the influence of surface heterogeneities that are not included in the models.
      In this regime, there can be significant differences between the predictions of
      the 1D and 2D models, which is due to the tendency of the contact line to slip
      more in the 1D model. The models are also used to understand the influence of
      initial bridge shape on liquid transfer and to rationalize related experimental
      observations. The results from these fundamental studies will aid the
      optimization of gravure and other printing processes for manufacturing of printed
      electronic devices.

PMID- 27714295
TI  - Synthesis of substituted indolizines via radical oxidative decarboxylative
      annulation of 2-(pyridin-2-yl)acetate derivatives with alpha,beta-unsaturated
      carboxylic acids.
AB  - A copper mediated radical oxidative annulation of 2-(pyridin-2-yl)acetate
      derivatives with alpha,beta-unsaturated carboxylic acids is developed. This study
      offers a new and expedient strategy for the synthesis of useful indolizines in
      moderate to good yields and exhibits a broad substrate scope and good functional
      group tolerance.

PMID- 27714296
TI  - Total synthesis of mangiferin, homomangiferin, and neomangiferin.
AB  - Total synthesis of mangiferin, homomangiferin, and neomangiferin, three C
      glycosyl xanthone natural products with a wide spectrum of pharmacological
      effects, has been achieved starting from 2,3,4,6-tetra-O-benzyl-alpha/beta-d
      glucopyranose. The key steps involve a stereoselective Lewis acid promoted C
      glycosylation of protected phloroglucinol with tetrabenzylglucopyranosyl acetate
      and a highly regioselective base-induced cyclization for the construction of the
      core xanthone skeleton.

PMID- 27714297
TI  - Structure-activity studies of non-steroid analogues structurally-related to
      neuroprotective estrogens.
AB  - Estrone and 17beta-estradiol are phenolic steroids that are known to be
      neuroprotective in multiple models of neuronal injury. Previous studies have
      identified the importance of their phenolic steroid A-ring for neuroprotection
      and have identified ortho substituents at the C-2 and C-4 positions on the phenol
      ring that enhance this activity. To investigate the importance of the steroid
      ring system for neuroprotective activity, phenolic compounds having the
      cyclopent[b]anthracene, cyclopenta[b]phenanthrene, benz[f]indene, benz[e]indene,
      indenes linked to a phenol, and a phenolic spiro ring system were prepared. New
      synthetic methods were developed to make some of the cyclopent[b]anthracene
      analogues as well as the spiro ring system. Compounds were evaluated for their
      ability to protect HT-22 hippocampal neurons from glutamate neurotoxicity and
      their activity relative to a potent neuroprotective analogue of 17beta-estradiol
      was determined. An adamantyl substituent placed ortho to the phenolic hydroxyl
      group gave neuroprotective analogues in all ring systems studied.

PMID- 27714298
TI  - Co-assembly of polyoxometalates and peptides towards biological applications.
AB  - The synergistic self-assembly of biomolecules with polyoxometalates (POMs) has
      recently been considered as an effective approach to construct nano-biomaterials
      with diverse structures and morphologies towards applications in drug delivery,
      controlled release, tissue engineering scaffolds, and biomineralization, due to
      the unique features of the clusters in addition to many well-known inorganic
      nanoparticles. This review presents an overview of recent work focusing on the
      noncovalent co-assembly of peptides and POMs as well as their biological
      applications. In the co-assemblies triggered by the interaction between the
      components significant advantages are observed that POMs or peptides alone do not
      possess; examples include chiral recognition of hybrid metal oxides, the quick
      hydrolysis of peptides, and enhanced inhibition of Abeta aggregation. Finally, we
      outline a brief perspective on possible unresolved issues and future
      opportunities in this field.

PMID- 27714299
TI  - Characterisation of 6-DMATSMo from Micromonospora olivasterospora leading to
      identification of the divergence in enantioselectivity, regioselectivity and
      multiple prenylation of tryptophan prenyltransferases.
AB  - Prenylated secondary metabolites including indole derivatives usually demonstrate
      improved biological and pharmacological activities, which make them promising
      candidates for drug discovery and development. The transfer reactions of a prenyl
      moiety from a prenyl donor, e.g. dimethylallyl diphosphate (DMAPP), to an
      acceptor is catalysed by prenyltransferases. One special group of such enzymes
      uses DMAPP and tryptophan as substrates with dimethylallyltryptophans as reaction
      products and functions therefore as dimethylallyltryptophan synthases (DMATSs).
      Sequence homology search with known tryptophan prenyltransferases from
      Streptomyces led to identification of a putative prenyltransferase gene MolI14.36
      in Micromonospora olivasterospora. Expression and biochemical investigations
      revealed that MolI14.36 acts as a tryptophan C6-prenyltransferase (6-DMATSMo).
      Study on substrate specificity of 6-DMATSMo displayed a significantly high
      activity towards d-tryptophan, which prompted us to carry out comparative studies
      on enantioselectivity, regioselectivity and multiple prenylation ability of
      additional DMATSs including FgaPT2, 5-DMATS, 5-DMATSSc, 6-DMATSSv, 6-DMATSSa and
      7-DMATS towards l- and d-isomers of tryptophan and their analogues. The relative
      activities of the tested enzymes towards d-tryptophan differ clearly from each
      other. Incubation of l-, d-isomers or the racemates of 5-, 6- and 7
      methyltryptophan revealed distinctly different preferences of the DMATS enzymes.
      Interestingly, 6-DMATSMo and 5-DMATSSc accepted 5-methyl-d-tryptophan much better
      than the l-enantiomer. Furthermore, the conversion yields of the d-isomers were
      strongly inhibited in the reactions with racemates. More interestingly, the
      regioselectivities of FgaPT2, 5-DMATSSc and 7-DMATS towards d-tryptophan and its
      C5-methylated derivative differed clearly from those of the l-forms. In addition,
      both mono- and diprenylated products were clearly detected for 5-DMATSSc with l-
      and d-enantiomers of tryptophan and their methylated derivatives.

PMID- 27714300
TI  - 4,4'-Bismoschamine: biomimetic synthesis and evidence to support structural
      equivalency to montamine.
AB  - The dimeric natural product montamine was originally reported as two N
      feruloylserotonin (moschamine) units linked by a nitrogen-nitrogen bond, but our
      recent synthesis of this symmetrical diacyl hydrazide structure revealed this to
      be incorrect. We subsequently hypothesized that the moschamine subunits were
      linked through the indole C4 site and that montamine was structurally identical
      to 4,4'-bismoschamine, a known natural product present in safflower oil. However,
      given that authentic samples of both montamine and 4,4'-bismoschamine were
      unavailable and that the NMR data for the natural products were recorded in
      different solvents, we were unable to unequivocally prove this hypothesis. A
      recent publication that claims montamine and 4,4'-bismoschamine are not the same
      natural product prompts us to disclose our own findings on this matter. A
      biomimetic synthesis of 4,4'-bismoschamine was developed that hinged on oxidative
      coupling of N-Boc-serotonin followed by elaboration of the resulting 4,4'-dimer
      to the natural product. A detailed comparison of the NMR data for synthetic 4,4'
      bismoschamine with that reported for montamine revealed that while the 1H NMR
      data were in good agreement, the 13C NMR data displayed some discrepancies. In
      light of this result, the NMR data for several literature compounds was analyzed,
      the results of which revealed that the upfield chemical shifts of the methylene
      protons in the 1H NMR of montamine is unique to 4,4'-bistryptamines, supporting
      our initial statement that montamine and 4,4'-bismoschamine are structurally
      equivalent. Given that the main differences in the 13C NMR data between montamine
      and synthetic 4,4'-bismoschamine occur at the quaternary carbons, we propose that
      these peaks have been misassigned from a 13C NMR spectrum that was obtained from
      an impure sample and/or the small amount of montamine (4 mg) isolated from the
      natural source.

PMID- 27714301
TI  - Design and synthesis of reversible solid-state photochromic pyrazolones by
      introducing a pyridine ring.
AB  - We demonstrate a new strategy for designing reversibility, fatigue resistance and
      fluorescence switching materials, which are based on pyrazolone derivatives by
      introducing a pyridine ring. The reversible "on" and "off" modulation of
      fluorescence emission was up to 95% in the solid state.

PMID- 27714302
TI  - Measuring the viscoelastic creep of soft samples by step response AFM.
AB  - We have measured the creep response of soft gels and cells after applying a step
      in loading force with atomic force microscopy (AFM). By analysing the creep
      response data using the standard linear solid model, we can quantify the viscous
      and elastic properties of these soft samples independently. Cells, in comparison
      with gels of similar softness, are much more viscous, as has been qualitatively
      observed in conventional force curve data before. Here, we quantify the spring
      constant and the viscous damping coefficient from the creep response data. We
      propose two different modes for applying a force step: (1) indirectly by
      increasing the sample height or (2) directly by employing magnetic cantilevers.
      Both lead to similar results, whereas the latter seems to be better defined since
      it resembles closely a constant strain mode. The former is easier to implement in
      most instruments, and thus may be preferable from a practical point of view.
      Creep analysis by step response is much more appropriate to analyse the
      viscoelastic response of soft samples like cells than the usually used force
      curve analysis.

PMID- 27714303
TI  - Correction: Total synthesis of fellutamides, lipopeptide proteasome inhibitors.
      More sustainable peptide bond formation.
AB  - Correction for 'Total synthesis of fellutamides, lipopeptide proteasome
      inhibitors. More sustainable peptide bond formation' by Michael C. Pirrung, et
      al., Org. Biomol. Chem., 2016, 14, 8367-8375.

PMID- 27714304
TI  - Force spectroscopy predicts thermal stability of immobilized proteins by
      measuring microbead mechanics.
AB  - Optimal immobilization of enzymes on porous microbeads enables the fabrication of
      highly active and stable heterogeneous biocatalysts to implement biocatalysis in
      synthetic and analytical chemistry. However, empirical procedures for enzyme
      immobilization still prevail over rational ones because there is an unmet need
      for more comprehensive characterization techniques that aid to understand and
      trace the immobilization process. Here, we present the use of atomic force
      spectroscopy (AFS) as an innovative solution to indirectly characterize
      immobilized proteins on porous materials and monitor the immobilization process
      in real time. We investigate the mechanical properties of porous agarose
      microbeads immobilizing proteins by indenting a colloidal probe (silica
      microparticle) into a single bead. AFS demonstrates that the binding of proteins
      to the solid matrix of an agarose microbead alters its stiffness. Interestingly,
      we discovered that irreversible and multivalent immobilizations that make
      microbeads stiffer also stabilize the immobilized proteins against the
      temperature. Hence, we propose atomic force spectroscopy as a useful technique to
      indirectly unravel the stability of the immobilized enzymes investigating the
      mechanics of the heterogenous biocatalysts as a solid biomaterial beyond the
      intrinsic mechanics of the proteins.

PMID- 27714305
TI  - Preparation of oxocene terpenes. The first enantiospecific synthesis of cytotoxic
      arenaran A.
AB  - The first syntheses of cytotoxic marine arenarans A and B starting from
      commercial (-)-sclareol are reported. The oxocene ring of the target compound is
      formed via ring-closing metathesis, a process that depends on certain structural
      requirements. The trans-fused structure of the natural product is confirmed by
      comparison with the cis-fused isomer, which was synthesized. This synthetic
      strategy is also applicable to the synthesis of other oxocene terpenes.

PMID- 27714306
TI  - Collective ratchet effects and reversals for active matter particles on quasi-one
      dimensional asymmetric substrates.
AB  - Using computer simulations, we study a two-dimensional system of sterically
      interacting self-mobile run-and-tumble disk-shaped particles with an underlying
      periodic quasi-one-dimensional asymmetric substrate, and show that a rich variety
      of collective active ratchet behaviors arise as a function of particle density,
      activity, substrate period, and the maximum force exerted by the substrate. The
      net dc drift, or ratchet transport flux, is nonmonotonic since it increases with
      increased activity but is diminished by the onset of self-clustering of the
      active particles. Increasing the particle density decreases the ratchet transport
      flux for shallow substrates but increases the ratchet transport flux for deep
      substrates due to collective hopping events. At the highest particle densities,
      the ratchet motion is destroyed by a self-jamming effect. We show that it is
      possible to realize reversals of the direction of the net dc drift in the deep
      substrate limit when multiple rows of active particles can be confined in each
      substrate minimum, permitting emergent particle-like excitations to appear that
      experience an inverted effective substrate potential. We map out a phase diagram
      of the forward and reverse ratchet effects as a function of the particle density,
      activity, and substrate properties.

PMID- 27714307
TI  - Synthesis and properties of novel 2'-C,4'-C-ethyleneoxy-bridged 2'
      deoxyribonucleic acids with exocyclic methylene groups.
AB  - Three 2'-C,4'-C-ethyleneoxy-bridged 2'-deoxyribonucleic acids possessing six
      membered bridges with 6'-oxygen and 8'-exocyclic methylene groups (methylene
      EoDNAs) were designed and synthesized in nine to ten steps from 5-methyluridine.
      The methylene-EoDNA-modified oligonucleotides showed excellent binding affinity
      with target ssRNA and extremely high nuclease resistance compared with natural
      oligonucleotides. These results proved the potential of methylene-EoDNAs for
      nucleic acid based technology.

PMID- 27714308
TI  - Abnormal polymer transport in crowded attractive micropost arrays.
AB  - We investigate polymer diffusion in a quasi-two-dimensional environment decorated
      with attractive cylindrical posts using Langevin dynamics simulation. We find
      that the polymer diffusivity has non-monotonic dependence on the post array
      density. This diffusive behavior strongly depends on the adsorption-desorption
      transition and the critical adsorption strength epsilonc. For epsilon < epsilonc,
      the polymer undergoes normal diffusion and the diffusivity decreases as the post
      density increases due to the reduction of the void volume. For epsilon >
      epsilonc, polymer dynamics is strongly mediated by post adsorption, and we
      observe a regime where the polymer diffusivity increases as the post density
      increases. The polymer diffusivity reaches a maximum, which can be attributed to
      cross-post translation enabled by large polymer conformation fluctuations. We
      find both cross-post transport and polymer conformation fluctuations strongly
      depend on the post absorption strength and the chain length.

PMID- 27714309
TI  - The self-assembly structure and the CO2-philicity of a hybrid surfactant in
      supercritical CO2: effects of hydrocarbon chain length.
AB  - Hybrid surfactants containing both fluorocarbon (FC) and hydrocarbon (HC) chains,
      as effective CO2-philic surfactants, could improve the solubility of polar
      substances in supercritical CO2. Varying the length of the HC of hybrid
      surfactants is an effective way to improve the CO2-philicity. In this paper, we
      have investigated the effects of the HC length on the self-assembly process and
      the CO2-philicity of hybrid surfactants (F7Hn, n = 1, 4, 7 and 10) in water/CO2
      mixtures using molecular dynamics simulations. It is found that the self-assembly
      time of F7Hn exhibits a maximum when the length of the HC is equal to that of the
      FC (F7H7). In this case, the investigation of H-bonds between the water core and
      CO2 phase shows that F7H7 has the strongest CO2-philicity because it has the best
      ability to separate water and CO2. To explain the origin of the differences in
      separation ability, the analysis of the structures of the reverse micelles shows
      that there are two competing mechanisms with a shortening HC. Firstly, the volume
      of F7Hn is reduced, which thus decreases the separation ability. Moreover, this
      also leads to the curved conformation of the FC. As a result, the separation
      ability is enhanced. These two mechanisms are balanced in F7H7, which has the
      best ability to separate water and CO2. Our simulation results demonstrate that
      the increased volume and the curved conformation of the hybrid surfactant tail
      could enhance the CO2-philicity in F7Hn surfactants. It is expected that this
      work will provide valuable information for the design of CO2-philic surfactants.

PMID- 27714310
TI  - Nile red fluorescence for quantitative monitoring of micropolarity and
      microviscosity of pluronic F127 in aqueous media.
AB  - The photophysical behaviour and excited state decay kinetics of the fluorescent
      probe Nile red were used for quantitative monitoring of micropolarity,
      microviscosity and the sol-gel transition temperature of a copolymer hydrogel,
      pluronic F127. There was considerable enhancement of the emission intensity with
      a large blue shift in emission and an absorption maximum at and above the sol-gel
      transition temperature (20  degrees C), showing the sensitivity of Nile red
      fluorescence to the sol-gel transition. The estimation of micropolarity by
      comparing the Nile red emission maximum in dioxane-water mixtures suggested a
      considerable decrease in the polarity of the PF127 microenvironment from less
      polar (20% dioxane-water) in its sol phase to almost non-polar (90% dioxane
      water) microenvironments in the gel phase. The thermotropic response of the
      wavelength dependent fluorescence lifetime of the probe with a rise time in the
      longer wavelength region has enabled monitoring of the microheterogeneity of the
      gel medium. With an increase in temperature, the microviscosity progressively
      increases from ~10 mPa s (sol state) to ~23 mPa s (gel state). The mismatch
      between microviscosity as estimated by the Nile red and the corresponding bulk
      viscosity reflected the microheterogeneity of the pluronic medium and its
      sensitivity towards PF127 microenvironments.

PMID- 27714311
TI  - On the syneresis of an OPV functionalised dipeptide hydrogel.
AB  - We describe a new dipeptide hydrogel based on an oligophenylene vinylene core.
      After gelation, the initial network evolves, expelling solvent and resulting in
      syneresis. We describe this process and the effects in the bulk properties of the
      material.

PMID- 27714312
TI  - Safety evaluation of repeated intravenous infusion of sinoporphyrin with and
      without PDT in rats.
AB  - Photodynamic therapy (PDT) is a promising antineoplastic modality in the oncology
      field. We assessed the safety of repeated intravenous administrations of
      sinoporphyrin, a porphyrin derivative, with and without illumination in rats.
      Toxicokinetic studies of single and multiple administrations of sinoporphyrin
      were also carried out. Sprague-Dawley rats were randomly assigned to the dark
      toxicity and PDT groups. Animals in the dark toxicity group received an i.v.
      infusion of sinoporphyrin at 3 doses: 2 mg kg-1, 6 mg kg-1, and 18 mg kg-1. The
      PDT group included 2 doses of sinoporphyrin (2 mg kg-1 and 18 mg kg-1), and the
      rats received 60 J of 630 nm laser illumination 24 h after photosensitizer
      infusion. The treatments were repeated every 7 days for 5 cycles and were
      followed by a 14-day recovery period. Systematic analyses were conducted at the
      end of treatment and recovery periods. Blood samples were obtained 5 min, 30 min,
      2 h, 8 h, 24 h, 48 h, 72 h, and 96 h after the first and fifth treatments for
      toxicokinetic studies. Sinoporphyrin-PDT led to the death of one out of 270 rats;
      the dead animal had been treated with 18 mg kg-1 sinoporphyrin and died at the
      end of the fifth PDT treatment. Liver injury, the primary toxicity observed in
      the study, was identified using biochemical tests, necropsy, and histopathology.
      Elevated white blood cell and neutrophil counts were found in the rats in both
      the dark toxicity and PDT groups. Skin lesions at the illumination site were
      obvious in the PDT group. Pigment deposits were detected in multiple organs such
      as the liver, spleen, lymph nodes, and ovaries in the 6 mg kg-1 and 18 mg kg-1
      groups. No other abnormalities were observed. The toxicokinetic parameters of
      single and multiple sinoporphyrin administrations were calculated and compared.
      Repeated sinoporphyrin administrations both alone and in combination with laser
      illumination were tolerable, and all toxicities were transient. The no observed
      adverse effect level (NOAEL) for repeated sinoporphyrin administration and
      sinoporphyrin-PDT was 6 mg kg-1 and 2 mg kg-1, respectively. Further studies are
      warranted.

PMID- 27714313
TI  - The role of UVR and vitamin D on T cells and inflammatory bowel disease.
AB  - Vitamin D deficiency is associated with the development of inflammatory bowel
      disease (IBD). In experimental IBD the targets of vitamin D that result in
      protection from IBD include gut epithelial cells, innate immune cells, T cells,
      and the microbiota. Ultraviolet radiation (UVR) induces production of vitamin D
      in the skin and suppresses T cell responses in the host. There is limited data
      demonstrating an effect of UVR on experimental IBD but the mechanisms of UVR
      suppression in IBD have not been defined. There are several shared effects of
      vitamin D and UVR on T cells including inhibition of proliferation and
      suppression of IFN-gamma and IL-17 producing T cells. Conversely UVR decreases
      and vitamin D increases IL-4 production from T cells. Together the data suggest
      that UVR suppression of T cells and potentially IBD are both vitamin D dependent
      and independent.

PMID- 27714314
TI  - Photocatalytic degradation of humic acid using a novel photocatalyst: Ce-doped
      ZnO.
AB  - This study aimed at investigating the photocatalytic degradation of humic acid
      (HA) as a representative of natural organic matter (NOM) by using Ce-doped ZnO as
      a novel material. Following photocatalysis, HA degradation was characterized by
      specified UV-vis and fluorescence spectroscopic parameters as well as by the
      dissolved organic carbon (NPOC) content. Excitation-Emission Matrix (EEM)
      fluorescence features were also evaluated by using advanced techniques.
      Comparison of Ce-doped ZnO photocatalysis to TiO2 P-25 photocatalytic treatment
      of the HA samples was elucidated under similar experimental conditions. Kinetic
      modeling of the photocatalytic removal of HA expressed promising results
      indicating that Ce-doped ZnO could serve as an efficient catalyst for the
      degradation of NOM.

PMID- 27714315
TI  - Shear dynamics of an inverted nematic emulsion.
AB  - Here we study theoretically the dynamics of a 2D and a 3D isotropic droplet in a
      nematic liquid crystal under a shear flow. We find a large repertoire of possible
      nonequilibrium steady states as a function of the shear rate and of the anchoring
      of the nematic director field at the droplet surface. We first discuss
      homeotropic anchoring. For weak anchoring, we recover the typical behaviour of a
      sheared isotropic droplet in a binary fluid, which rotates, stretches and can be
      broken by the applied flow. For intermediate anchoring, new possibilities arise
      due to elastic effects in the nematic fluid. We find that in this regime the 2D
      droplet can tilt and move in the flow, or tumble incessantly at the centre of the
      channel. For sufficiently strong anchoring, finally, one or both of the
      topological defects which form close to the surface of the isotropic droplet in
      equilibrium detach from it and get dragged deep into the nematic state by the
      flow. In 3D, instead, the Saturn ring associated with the normal anchoring
      disclination line can be deformed and shifted downstream by the flow, but remains
      always localized in the proximity of the droplet, at least for the parameter
      range we explored. Tangential anchoring in 2D leads to a different dynamic
      response, as the boojum defects characteristic of this situation can unbind from
      the droplet under a weaker shear with respect to the normal anchoring case. Our
      results should stimulate further experiments with inverted liquid crystal
      emulsions under shear, as most of the predictions can be testable in principle by
      monitoring the evolution of liquid crystalline orientation patterns or by
      tracking the position and shape of the droplet over time.

PMID- 27714316
TI  - Red-emitting protein-coated conjugated polymer nanoparticles.
AB  - Red emitting materials are desirable in biology due to the transparency of
      certain biological tissues at these wavelengths. Here, we report the synthesis of
      aqueous dispersions of amphiphilic protein (hydrophobin) capped red-emitting
      cyano-substituted poly(p-phenylenevinylene) conjugated polymer nanoparticles
      (CPNs) and their use in labeling live mammalian (HeLa) cells.

PMID- 27714317
TI  - Conformational studies of 10-23 DNAzyme in solution through pyrenyl-labeled 2'
      deoxyadenosine derivatives.
AB  - 10-23 DNAzyme is a small catalytic DNA molecule. Studies on its conformation in
      solution are critical for understanding its catalytic mechanism and functional
      optimization. Based on our previous research, two fluorescent nucleoside
      analogues 1 and 2 were designed for the introduction of a pyrenyl group at one of
      the five dA residues in the catalytic core and the unpaired adenosine residue in
      its full-DNA substrate, respectively. Ten pyrenyl-pyrenyl pairs are formed in the
      DNAzyme-substrate complexes in solution for sensing the spacial positions of the
      five dA residues relative to the cleavage site using fluorescence spectra. The
      position-dependent quenching effect of pyrene emission fluorescence by
      nucleobases, especially the pyrenyl-pyrenyl interaction, was observed for some
      positions. The adenine residues in the 3'-part of the catalytic loop seem to be
      closer to the cleavage site than the adenine residues in the 5'-part, which is
      consistent with the molecular dynamics simulation result. The catalytic
      activities and Tm changes also confirmed the effect of the pyrenyl-nucleobase and
      pyrenyl-pyrenyl pair interactions. Together with functional group mutations,
      catalytically relevant nucleobases will be identified for understanding the
      catalytic mechanism of 10-23 DNAzyme.

PMID- 27714318
TI  - Negative stiffness and modulated states in active nematics.
AB  - We examine the dynamics of an active nematic liquid crystal on a frictional
      substrate. When frictional damping dominates over viscous dissipation, we
      eliminate flow in favor of active stresses to obtain a minimal dynamical model
      for the nematic order parameter, with elastic constants renormalized by activity.
      The renormalized elastic constants can become negative at large activity, leading
      to the selection of spatially inhomogeneous patterns via a mechanism analogous to
      that responsible for modulated phases arising at an equilibrium Lifshitz point.
      Tuning activity and the degree of nematic order in the passive system, we obtain
      a linear stability phase diagram that exhibits a nonequilibrium tricritical point
      where ordered, modulated and disordered phases meet. Numerical solution of the
      nonlinear equations yields a succession of spatial structures of increasing
      complexity with increasing activity, including kink walls and active turbulence,
      as observed in experiments on microtubule bundles confined at an oil-water
      interface. Our work provides a minimal model for an overdamped active nematic
      that reproduces all the nonequilibrium structures seen in simulations of the full
      active nematic hydrodynamics and provides a framework for understanding some of
      the mechanisms for selection of the nonequilibrium patterns in the language of
      equilibrium critical phenomena.

PMID- 27714319
TI  - About different packing states of alkyl groups in comb-like polymers with rigid
      backbones.
AB  - We report a comparative X-ray diffraction study on three series of comb-like
      polymers with rigid backbones and layered morphologies [regio-regular poly(3
      alkyl thiophenes), alkoxylated polyesters, alkoxylated polyphenylenevinylenes]
      highlighting the importance of the volume per methylene unit VCH2 in alkyl
      nanodomains for the overall packing state. We demonstrate that there is a large
      (~30%) variation in the VCH2 values for different polymer series and packing
      states but no significant change in VCH2 depending on the length of the alkyl
      side groups. This calls into question commonly used structural models which are
      based only on tilting and interdigitation of ideally stretched alkyl side groups.
      We argue that a linear dependence of the layer spacings with side chain length
      can also be explained by a constant VCH2 value and unchanged main chain packing.
      The potential importance of side chain packing for the occurrence of different
      (liquid-) crystalline modifications in various polymer series and possible
      interrelations between main and side chain packings are discussed.

PMID- 27714320
TI  - Sonochemical/hydration-dehydration synthesis of Pt-TiO2 NPs/decorated carbon
      nanotubes with enhanced photocatalytic hydrogen production activity.
AB  - Modified Pt-TiO2 NPs/decorated carbon nanotubes were synthesized utilizing
      sonochemical/hydration-dehydration techniques. Pt was loaded on TiO2 by a
      photodeposition method keeping in mind the end goal to achieve electron-hole pair
      separation and promote the surface reaction. The morphological and basic
      properties of Pt-TiO2/fCNTs were investigated by field emission scanning electron
      microscopy (FESEM), high resolution transmission electron microscopy (HRTEM),
      powder X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (DRS),
      photoluminescence (PL) and Raman spectroscopy. The selected area electron
      diffraction (SAED) patterns of Pt-TiO2/fCNTs were obtained utilizing TEM-based
      energy dispersive X-ray spectroscopy (EDXS) analysis. It was found that the TiO2
      nanoparticles were uniformly distributed on the fCNTs, and the Pt particles were
      decorated on the surface of TiO2/fCNTs. The photocatalytic hydrogen production
      activity of the Pt(0.5%)-TiO2/fCNTs(0.5%) nanoparticle composites was
      investigated using a sacrificial agent methanol solution. Pt-loaded TiO2
      demonstrated a hydrogen evolution rate around 20 times that of TiO2/fCNTs(0.5%)
      (fSWCNTs, fMWCNTs). When compared with platinized TiO2 in methanol, which was
      utilized as a control material, Pt-TiO2/fCNTs demonstrated an almost 2-fold
      increment in hydrogen generation.

PMID- 27714321
TI  - A Prussian blue/carbon dot nanocomposite as an efficient visible light active
      photocatalyst for C-H activation of amines.
AB  - A Prussian blue/carbon dot (PB/CD) nanocomposite was synthesised and used as a
      visible-light active photocatalyst for the oxidative cyanation of tertiary amines
      to alpha-aminonitriles by using NaCN/acetic acid as a cyanide source and H2O2 as
      an oxidant. The developed photocatalyst afforded high yields of products after 8
      h of visible light irradiation at room temperature. The catalyst was recycled and
      reused several times without any significant loss in its activity.

PMID- 27714322
TI  - Spectroscopic studies of the interaction of 3-(2-thienyl)-[1,2,3]triazolo[1,5
      a]pyridine with 2,6-dimethyl-beta-cyclodextrin and ctDNA.
AB  - The inclusion complexation behavior of 3-(2-thienyl)-[1,2,3]triazolo[1,5-a]
      pyridine (TTP) with native beta-cyclodextrin and derivatized cyclodextrins was
      investigated. Stability constants for complexes with 1 : 1 molar ratios were
      calculated from phase solubility diagrams. The solubilizing efficiency of the TTP
      inclusion complex is enhanced in the order of DMbetaCD > HPbetaCD > betaCD. The
      TTP-DMbetaCD inclusion complex was further characterized in solution by means of
      absorption, fluorescence, 2D NMR and molecular modeling methods. The
      thermodynamic studies indicate that the inclusion of TTP into the cyclodextrin
      cavity is mainly an enthalpy-driven process. The 2D NMR studies revealed that the
      thienyl moiety of TTP is inserted into the CD cavity while the triazolopyridine
      protrudes the primary rim of the DMbetaCD, which are in good agreement with
      docking results. The fluorescence titration of TTP by ctDNA suggested that the
      quenching mechanism is a dynamic quenching procedure resulting from the
      temperature dependence of the TTP-ctDNA complex. Thermodynamics of the
      interaction revealed that the positive values of DeltaH and DeltaS announced that
      the binding process was primarily driven by hydrophobic forces indicating that
      TTP interacts with ctDNA by means of the minor groove. These results are in good
      agreement with docking experiments and iodide experiments which reinforce TTP's
      interactions in the minor groove.

PMID- 27714323
TI  - Mesoporous self-assembled nanoparticles of biotransesterified cyclodextrins and
      nonlamellar lipids as carriers of water-insoluble substances.
AB  - Soft mesoporous hierarchically structured particles were created by the self
      assembly of an amphiphilic deep cavitand cyclodextrin betaCD-nC10 (degree of
      substitution n = 7.3), with a nanocavity grafted by multiple alkyl (C10) chains
      on the secondary face of the betaCD macrocycle through enzymatic
      biotransesterification, and the nonlamellar lipid monoolein (MO). The effect of
      the non-ionic dispersing agent polysorbate 80 (P80) on the liquid crystalline
      organization of the nanocarriers and their stability was studied in the context
      of vesicle-to-cubosome transition. The coexistence of small vesicular and
      nanosponge membrane objects with bigger nanoparticles with inner multicompartment
      cubic lattice structures was established as a typical feature of the employed
      dispersion process. The cryogenic transmission electron microscopy (cryo-TEM)
      images and small-angle X-ray scattering (SAXS) structural analyses revealed the
      dependence of the internal organization of the self-assembled nanoparticles on
      the presence of embedded betaCD-nC10 deep cavitands in the lipid bilayers. The
      obtained results indicated that the incorporated amphiphilic betaCD-nC10 building
      blocks stabilize the cubic lattice packing in the lipid membrane particles, which
      displayed structural features beyond the traditional CD nanosponges. UV-Vis
      spectroscopy was employed to characterize the nanoencapsulation of a model
      hydrophobic dimethylphenylazo-naphthol guest compound (Oil red) in the created
      nanocarriers. In perspective, these dual porosity carriers should be suitable for
      co-encapsulation and sustained delivery of peptide, protein or siRNA
      biopharmaceuticals together with small molecular weight drug compounds or imaging
      agents.

PMID- 27714324
TI  - Blast wave attenuation in liquid foams: role of gas and evidence of an optimal
      bubble size.
AB  - Liquid foams are excellent systems to mitigate pressure waves such as acoustic or
      blast waves. The understanding of the underlying dissipation mechanisms however
      still remains an active matter of debate. In this paper, we investigate the
      attenuation of a weak blast wave by a liquid foam. The wave is produced with a
      shock tube and impacts a foam, with a cylindrical geometry. We measure the wave
      attenuation and velocity in the foam as a function of bubble size, liquid
      fraction, and the nature of the gas. We show that the attenuation depends on the
      nature of the gas and we experimentally evidence a maximum of dissipation for a
      given bubble size. All features are qualitatively captured by a model based on
      thermal dissipation in the gas.

PMID- 27714325
TI  - Light harvesting a gold porphyrin-zinc phthalocyanine supramolecular donor
      acceptor dyad.
AB  - We reported herein the spectroscopic, electrochemical and laser photolysis
      studies for the newly constructed light harvesting supramolecular dyad composed
      of gold porphyrin (AuPpy), as an electron acceptor, and zinc phthalocyanine
      (ZnPc), as an electron donor, to mimic the reaction centre in the photosynthetic
      system. For this, gold porphyrin has been functionalized by pyridine units, which
      axially coordinated with zinc phthalocyanine to form the stable supramolecular
      AuPpy:ZnPc with a rate of 2.94 * 104 M-1. Steady-state fluorescence measurements
      showed significant quenching of the singlet excited ZnPc emission with addition
      of AuPpy, suggesting an electron transfer from the singlet excited ZnPc to AuPpy.
      The electron transfer character was confirmed by recoding the characteristic
      absorption band of the zinc phthalocyanine radical cation in the NIR region by a
      femtosecond laser photolysis technique. The findings that the AuPpy:ZnPc
      supramolecular dyad exhibits relatively long-lived radical-ion pairs and absorbs
      light in a wide range of the solar spectrum suggest that it would be useful as a
      photosynthetic reaction centre.

PMID- 27714326
TI  - Formation of simple single-tailed vesicles mediated by lipophilic solid surfaces.
AB  - Adsorption and aggregation of surfactants at solid-liquid interfaces were fairly
      well understood, but there was limited knowledge regarding the effect of the
      presence of a solid surface on aggregate structures in bulk solution. Except for
      the fatty acid system, most simple single-tailed surfactants (STSs) are well
      known to form micelles but not vesicles in aqueous solution. Herein, we report a
      novel phenomenon: with the mediation of lipophilic solid surfaces (LSSs), the
      zwitterionic STS lauryl sulfobetaine (LSB) formed vesicles from its micellar
      solution without any additives, producing a mixed solution of vesicles and
      micelles. More interestingly, the STS vesicles coexisted stably with micelles in
      the solution and were thermally insensitive even after the removal of LSSs. The
      quantity of LSB vesicles decreases with the addition of ethanol. The pH effects
      (4.0-9.0) did not have an obvious influence on the formation and stability of the
      LSB vesicles. Similar results were obtained from the other STSs, suggesting that
      the LSS-mediated micelle-to-vesicle transition may be a general phenomenon. We
      proposed a possible mechanism that adsorption, the matrix effect, and
      interdigitated bilayer structures were probably crucial for the formation and
      stability of STS vesicles. We expect this work to provide important insights into
      the effect of the solid/liquid interface on the self-assembly chemistry of
      surfactants in bulk solution.

PMID- 27714327
TI  - Computational insight into the cooperative role of non-covalent interactions in
      the aza-Henry reaction catalyzed by quinine derivatives: mechanism and
      enantioselectivity.
AB  - Density functional theory (DFT) calculations were performed to elucidate the
      mechanism and the origin of the high enantioselectivity of the aza-Henry reaction
      of isatin-derived N-Boc ketimine catalyzed by a quinine-derived catalyst (QN).
      The C-C bond formation step is found to be both the rate-determining and the
      stereo-controlled step. The results revealed the important role of the phenolic
      OH group in pre-organizing the complex of nitromethane and QN and stabilizing the
      in situ-generated nitronate and protonated QN. Three possible activation modes
      for C-C bond formation involving different coordination patterns of catalyst and
      substrates were studied, and it was found that both the ion pair-hydrogen bonding
      mode and the Bronsted acid-hydrogen bonding mode are viable, with the latter
      slightly preferred for the real catalytic system. The calculated enantiomeric
      excess (ee) favouring the S enantiomer is in good agreement with the experimental
      result. The high reactivity and enantioselectivity can be ascribed to the
      cooperative role of the multiple non-covalent interactions, including classical
      and non-classical H bonding as well as anionpi interactions. These results also
      highlight the importance of the inclusion of dispersion correction for achieving
      a reasonable agreement between theory and experiment for the current reaction.

PMID- 27714328
TI  - Dynamics of liquid plugs in prewetted capillary tubes: from acceleration and
      rupture to deceleration and airway obstruction.
AB  - The dynamics of individual liquid plugs pushed at a constant pressure head inside
      prewetted cylindrical capillary tubes is investigated experimentally and
      theoretically. It is shown that, depending on the thickness of the prewetting
      film and the magnitude of the pressure head, the plugs can either experience a
      continuous acceleration leading to a dramatic decrease of their size and
      eventually their rupture or conversely, a progressive deceleration associated
      with their growth and an exacerbation of the airway obstruction. These behaviors
      are quantitatively reproduced using a simple nonlinear model [Baudoin et al.,
      Proc. Natl. Acad. Sci. U. S. A., 2013, 110, 859] adapted here for cylindrical
      channels. Furthermore, an analytical criterion for the transition between these
      two regimes is derived and successfully compared with extensive experimental
      data. The potential implications of this work for pulmonary obstructive diseases
      are discussed.

PMID- 27714329
TI  - Total synthesis of wewakazole B.
AB  - Wewakazole B is a novel cyclodecapeptide with highly potent cytotoxic activity
      isolated from a sample of M. producens collected from the Red Sea. It contains
      nine common and three modified amino acid residues. The first total synthesis of
      Wewakazole B was successfully achieved on a gram scale, unambiguously confirming
      its structure. Notable features include the careful choice of amino acid
      protecting groups and the construction of three different substituted oxazoles
      present in this natural product.

PMID- 27714330
TI  - Controlling swelling/deswelling of stimuli-responsive hydrogel nanofilms in
      electric fields.
AB  - The swelling/deswelling transition of pH-sensitive, electrode-grafted, hydrogel
      nanofilms when exposed to electric fields is studied by theoretical analysis. In
      acidic conditions, the response of these films to changes in pH is dominated by
      network-surface interactions, while intra-network electrostatic repulsions, which
      are highly modulated by the adsorption of salt ions, determine material response
      at a higher pH. Film thickness is a non-monotonic function of solution pH and
      displays a local maximum, a local minimum or both, depending on the salt
      concentration and the applied voltage. We suggest the use of these materials in
      the development of biosensors and control of enzyme activity.

PMID- 27714331
TI  - A practical metal-free homolytic aromatic alkylation protocol for the synthesis
      of 3-(pyrazin-2-yl)bicyclo[1.1.1]pentane-1-carboxylic acid.
AB  - As a part of our ongoing synthetic quest to expand the frontiers of contemporary
      medicinal chemistry, we now report an expedient synthesis of a potentially useful
      bicyclo[1.1.1]pentane building block, 3-(pyrazin-2-yl)bicyclo[1.1.1]pentane-1
      carboxylic acid. This report also showcases the application of this motif as a
      probe in a biological study.

PMID- 27714332
TI  - Magnetic field induced modulated phases in a ferrofluid lutidine silicone oil
      mixture.
AB  - A mixture of an ester based ferrofluid with silicone oil and 2,6-lutidine is
      exposed to an external magnetic field. We find a region of composition of the
      ternary mixture, where weak magnetic fields of the order of a few kA m-1 induce a
      modulated phase with a pattern characterized by equilibrium size droplets of the
      minority phase immersed into the extended majority phase. While the pattern
      resembles in many ways the pattern of immiscible magnetic fluids, the dependence
      of the characteristic parameters of the pattern on the magnetic field are
      completely different than in immiscible fluids. We theoretically explain the
      pattern formation as a magnetic field induced polymerization of magnetic
      particles into magnetic chains that goes along with a reduction of the entropy of
      mixing. This entropy reduction causes the Ostwald ripening of chains into
      mesoscopic droplets the size of which is limited by repulsive dipolar
      interactions between the chains.

PMID- 27714333
TI  - Interfacial rheology of polymer/carbon nanotube films co-assembled at the
      oil/water interface.
AB  - At appropriate conditions, water-dispersed acid-functionalized single-walled
      carbon nanotubes (SWCNTs) co-assemble at the oil/water interface with toluene
      dissolved amine-terminated polystyrene (PS-NH2) to form composite thin films
      displaying pronounced interfacial viscoelasticity. To probe this viscoelasticity,
      the films were examined under dilatational deformations of pendant drop
      tensiometry/rheometry, with storage and loss moduli recorded against frequency
      omega (0.003 < omega < 3 Hz) and time-dependent relaxation modulus recorded
      against time t (0.2 < t < 2000 s). Without the SWCNTs, PS-NH2-decorated
      interfaces have little dilatational stiffness, i.e., low storage modulus, but
      their stiffness grows as SWCNTs are added, reaching 50-100 mN m-1 at large omega.
      Two characteristic relaxation processes are identified in the composite films: a
      fast process (omega ~ 0.1-0.2 Hz) attributable to local structural relaxation of
      confined PS-NH2 and a slow process (t ~ 300-2000 s) attributable to component
      adsorption/desorption (or attachment/detachment). Among the variables that affect
      positions and strengths of these relaxations are SWCNT and PS-NH2 bulk
      concentrations as well as water phase pH. In frequency or timescale ranges
      intermediate between the two relaxations, the co-assembled films display "soft
      glass" behavior, with the storage and loss moduli characterized by nearly equal
      power-law exponents. The relaxation modulus, better able to probe terminal
      behavior, eventually decays to zero, revealing that the films are fundamentally
      fluid-like due to the slow relaxation, and in support of this conclusion, large
      strain compression-induced film wrinkles disappear at large t.

PMID- 27714334
TI  - Poroelastic indentation of mechanically confined hydrogel layers.
AB  - We report on the poroelastic indentation response of hydrogel thin films
      geometrically confined within contacts with rigid spherical probes of radii in
      the millimeter range. Poly(PEGMA) (poly(ethylene glycol) methyl ether
      methacrylate), poly(DMA) (dimethylacrylamide) and poly(NIPAM) (N
      isopropylacrylamide) gel films with thickness less than 15 MUm were grafted onto
      glass substrates using a thiol-ene click chemistry route. Changes in the
      indentation depth under constant applied load were monitored over time as a
      function of the film thickness and the radius of curvature of the probe using an
      interferometric method. In addition, shear properties of the indented films were
      measured using a lateral contact method. In the case of poly(PEGMA) films, we
      show that poroelastic indentation behavior is adequately described within the
      framework of an approximate contact model derived within the limits of confined
      contact geometries. This model provides simple scaling laws for the
      characteristic poroelastic time and the equilibrium indentation depth.
      Conversely, deviations from this model are evidenced for poly(DMA) and
      poly(NIPAM) films. From lateral contact experiments, these deviations are found
      to result from strong changes in the shear properties as a result of glass
      transition (poly(DMA)) or phase separation (poly(NIPAM)) phenomena induced by the
      drainage of the confined films squeezed between the rigid substrates.

PMID- 27714335
TI  - Clusters of red blood cells in microcapillary flow: hydrodynamic versus
      macromolecule induced interaction.
AB  - We present experiments on RBCs that flow through micro-capillaries under
      physiological conditions. The strong flow-shape coupling of these deformable
      objects leads to a rich variety of cluster formation. We show that the RBC
      clusters form as a subtle imbrication between hydrodynamic interactions and
      adhesion forces because of plasma proteins, mimicked by the polymer dextran.
      Clusters form along the capillaries and macromolecule-induced adhesion
      contributes to their stability. However, at high yet physiological flow
      velocities, shear stresses overcome part of the adhesion forces, and cluster
      stabilization due to hydrodynamics becomes stronger. For the case of pure
      hydrodynamic interaction, cell-to-cell distances have a pronounced bimodal
      distribution. Our 2D-numerical simulations on vesicles capture the transition
      between adhesive and non-adhesive clusters at different flow velocities.

PMID- 27714336
TI  - Nanotubular self-organization of amide dendrons with focal beta-sheet forming
      peptide units.
AB  - To develop rational design principles for a self-organized structure using
      dendron-peptide conjugates, a beta-sheet forming short peptide (VVLL) was
      introduced to the focal point of a second-generation amide dendron (2G-VVLL) and
      its self-organization characteristics were investigated. 2G-VVLL self-organized
      into a nanotubular structure in the aqueous phase. The twisted beta-sheet
      structure of the focal peptide unit was essential for the construction of the
      nanotubular structure. The design principle could be applied to another dendron
      peptide conjugate (2G-AAVV). These findings are expected to assist in the
      construction of novel precisely controlled nanoarchitectures using amide dendrons
      with focal peptide units.

PMID- 27714337
TI  - One-step formation of multiple Pickering emulsions stabilized by self-assembled
      poly(dodecyl acrylate-co-acrylic acid) nanoparticles.
AB  - In this study, a one-step generation of stable multiple Pickering emulsions using
      pH-responsive polymeric nanoparticles as the only emulsifier was reported. The
      polymeric nanoparticles were self-assembled from an amphiphilic random copolymer
      poly(dodecyl acrylate-co-acrylic acid) (PDAA), and the effect of the copolymer
      content on the size and morphology of PDAA nanoparticles was determined by
      dynamic light scattering (DLS) and transmission electron microscopy (TEM). The
      emulsification study of PDAA nanoparticles revealed that multiple Pickering
      emulsions could be generated through a one-step phase inversion process by using
      PDAA nanoparticles as the stabilizer. Moreover, the emulsification performance of
      PDAA nanoparticles at different pH values demonstrated that multiple emulsions
      with long-time stability could only be stabilized by PDAA nanoparticles at pH
      5.5, indicating that the surface wettability of PDAA nanoparticles plays a
      crucial role in determining the type and stability of the prepared Pickering
      emulsions. Additionally, the polarity of oil does not affect the emulsification
      performance of PDAA nanoparticles, and a wide range of oils could be used as the
      oil phase to prepare multiple emulsions. These results demonstrated that multiple
      Pickering emulsions could be generated via the one-step emulsification process
      using self-assembled polymeric nanoparticles as the stabilizer, and the prepared
      multiple emulsions have promising potential to be applied in the cosmetic,
      medical, and food industries.

PMID- 27714338
TI  - Nanostickers for cells: a model study using cell-nanoparticle hybrid aggregates.
AB  - We present direct evidence that nanoparticles (NPs) can stick together cells that
      are inherently non-adhesive. Using cadherin-depleted S180 murine cells lines,
      which exhibit very low cell-cell adhesion, we show that NPs can assemble
      dispersed single cells into large cohesive aggregates. The dynamics of
      aggregation, which is controlled by diffusion and collision, can be described as
      a second-order kinetic law characterized by a rate of collision that depends on
      the size, concentration, and surface chemistry of the NPs. We model the cell-cell
      adhesion induced by the "nanostickers" using a three-state dynamical model, where
      the NPs are free, adsorbed on the cell membrane or internalized by the cells. We
      define a "sticking efficiency parameter" to compare NPs and look for the most
      efficient type of NP. We find that 20 nm carboxylated polystyrene NPs are more
      efficient nanostickers than 20 nm silica NPs which were reported to induce fast
      wound healing and to glue soft tissues. Nanostickers, by increasing the cohesion
      of tissues and tumors, may have important applications for tissue engineering and
      cancer treatment.

PMID- 27714339
TI  - Curvature induced hierarchical wrinkling patterns in soft bilayers.
AB  - Sinusoidal wrinkling will occur in a planar film-substrate bilayer when the
      uniaxial compressive strain imposed to the system exceeds a critical value.
      However, when a core-shell soft cylinder is subjected to axial compression,
      surface wrinkling patterns may evolve from the sinusoidal mode to the diamond
      like mode, depending on the modular ratio and the curvature of the system.
      Inspired by this phenomenon, we here propose a simple yet robust strategy to
      fabricate hierarchical wrinkling patterns by controlling the curvature of a film
      substrate system. To quantitatively understand the experimental results, a three
      dimensional finite element model has been built to track the wrinkling pattern
      evolution. Furthermore, a phase diagram is provided based on the theoretical
      analysis and finite element simulations, which may guide the experimental design.
      In addition, the wetting properties of the surface with hierarchical
      micropatterns fabricated using the proposed method are investigated. The results
      show that the hierarchical surface wrinkles lead to anisotropic wetting behavior,
      which can be tuned by controlling the imposed compressive strain. The tunable
      anisotropic wetting surface fabricated here may find a broad range of
      applications such as in the development of sensors, fluidic devices, micro
      reactors and biomedical devices.

PMID- 27714340
TI  - The unique role of bond length in the glassy dynamics of colloidal polymers.
AB  - Bond length is generally not considered as a controllable variable for molecular
      polymers. Hence, no experimental, simulation or theoretical research, to our
      knowledge, has examined the influence of bond length on the glassy dynamics of
      polymers. Recently, a new class of assembling materials called "colloidal
      polymers" has been synthesized. These colloidal polymers have advantages over
      molecular polymers in the visibility and flexibility of tuning, for example, the
      size and shape of the "monomers", the interaction, and the bond length. Dense
      suspension of colloidal polymers will become a very promising ideal model system
      for exploring the fundamental problems in the glass transition of chain
      "molecules". Here, we study the static structure and activated dynamics of hard
      sphere colloidal polymers by generalizing the colloidal nonlinear Langevin
      equation theory to colloidal polymers. Surprisingly, we find that the bond length
      plays a critical and unique role in many aspects. For instance, the universal
      relations of the characteristic local lengths and the activated barrier versus
      the "degree of supercooling", and the structural relaxation versus local
      vibrational motion are found to be dependent on bond length and independent of
      chain length and rigidity. We hope that our findings inspire future experimental
      and simulation research studies on the glassy dynamics of colloidal polymers.

PMID- 27714341
TI  - Humic-like substances from urban waste as auxiliaries for photo-Fenton treatment:
      a fluorescence EEM-PARAFAC study.
AB  - In this work, analysis of excitation-emission-matrices (EEM) has been employed to
      gain further insight into the characterization of humic like substances (HLS)
      obtained from urban wastes (soluble bio-organic substances, SBOs). In particular,
      complexation of these substances with iron and changes along a photo-Fenton
      process have been studied. Recorded EEMs were decomposed by using parallel factor
      analysis (PARAFAC). Three fluorescent components were identified by PARAFAC
      modeling of the entire set of SBO solutions studied. The EEM peak locations
      (lambdaex/lambdaem) of these components were 310-330 nm/400-420 nm (C1), 340-360
      nm/450-500 nm (C2), and 285 nm/335-380 nm (C3). Slight variations of the maximum
      position of each component with the solution pH were observed. The interaction of
      SBO with Fe(iii) was characterized by determining the stability constants of the
      components with Fe(iii) at different pH values, which were in the order of
      magnitude of the ones reported for humic substances and reached their highest
      values at pH = 5. Photochemical experiments employing SBO and Fe(iii), with and
      without H2O2, showed pH-dependent trends for the evolution of the modeled
      components, which exhibited a strong correlation with the efficiency reported for
      the photo-Fenton processes in the presence of SBO at different pH values.

PMID- 27714342
TI  - Understanding the role of molar mass and stirring in polymer dissolution.
AB  - When a dry soluble polymer is put in contact with a large quantity of solvent, it
      swells and forms a transient gel, and eventually, yields a dilute solution of
      polymers. Everyday lab experience shows that when the molar mass is large, namely
      tens of times larger than entanglement mass, this dissolution process is slow and
      difficult and may require stirring. Here, in agreement with previous results, we
      found that the time needed to turn a dry grain into a dilute solution is not
      limited by water diffusion in the glassy or semi-crystalline dry polymer, but
      rather by the life-time of the transient gel made of entangled chains. In
      addition, we shed new light on the dissolution process by demonstrating that, in
      contrast to theoretical predictions, the gel life-time is not governed by
      reptation. We show instead that swelling is simply controlled by the osmotic
      pressure and the gel permeability until the overlap concentration is reached
      within the gel. At this stage, the gel turns into a dilute solution in which
      polymers are dispersed by natural convection. The observed dependence of the
      dissolution process on the molar mass therefore originates from the molar mass
      dependent overlap concentration. Under stirring, or forced convection, the
      polymer gel disappears at a higher critical concentration that depends on the
      shear rate. We suggest a description of the experimental data which uses the
      rheological flow curves of the solutions of the considered polymer. Inversely,
      dissolution times of polymer powders under stirring can be inferred from
      classical rheological measurements of the polymer solutions at varied
      concentrations.

PMID- 27714343
TI  - Evolution of hierarchical porous structures in supramolecular guest-host
      hydrogels.
AB  - Macromolecular interactions are used to form supramolecular assemblies, including
      through the interaction of guest-host chemical pairs. Microstructural
      heterogeneity has been observed within such physical hydrogels; yet, systematic
      investigation of the microstructure and its determining inputs are lacking.
      Herein, we investigated the hierarchical self-assembly of hyaluronic acid (HA)
      modified by the guest-host pair adamantane (Ad-HA, guest) and beta-cyclodextrin
      (CD-HA, host), as well as with methacrylate groups to both tether fluorescent
      agents and to covalently stabilize the material structure. We observed
      microporous materials in the hydrated state, which temporally arose from
      initially homogenous hydrogels composed of the two polymers. Independent
      fluorescent labeling of Ad-HA and CD-HA demonstrated spatiotemporal co
      localization, indicative of guest-host polymer condensation on the microscale.
      The hydrogel void fractions and pore diameters were independently tuned through
      incubation time (0-7 days), polymer concentration (1.25-10 wt%), and polymer
      modification (25-50% Ad-HA modification). Void fractions as great as 93.3 +/-
      2.4% were achieved and pore diameters ranged from 2.1 +/- 0.5 to 1025.4 +/- 209.4
      MUm. The segregation of discrete solid and solute phases was measured with both
      atomic force microscopy and diffusive microparticle tracking analysis, where the
      solute phase contained only dilute polymer. The study represents a systematic
      investigation of hierarchical self-assembly in binary associating hydrogels, and
      provides insights on mechanisms that control microstructure within supramolecular
      hydrogels.

PMID- 27714344
TI  - Correction: Frustrated phases under three-dimensional confinement simulated by a
      set of coupled Cahn-Hilliard equations.
AB  - Correction for 'Frustrated phases under three-dimensional confinement simulated
      by a set of coupled Cahn-Hilliard equations' by Edgar Avalos et al., Soft Matter,
      2016, 12, 5905-5914.

PMID- 27714345
TI  - Evaporation-induced self-assembly of quantum dots-based concentric rings on
      polymer-based nanocomposite films.
AB  - The "ball-on-film" template is used to construct concentric rings on the surface
      of PMMA-QDs (polymethyl methacrylate - quantum dots) nanocomposite films via the
      evaporation of pure chloroform droplets, which are confined by a steel ball. The
      concentric rings consist of QDs, as revealed by the fluorescence images of the
      concentric rings. The photoluminescence intensity of the concentric rings
      increases with the increase of the distance to the ball center, suggesting that
      the amount of QDs accumulated around the contact line at individual stick state
      increases with the increase of the distance to the ball center. Both the
      wavelength and cross-sectional area (width) of the concentric rings increase
      approximately linearly with increasing distance to the ball center, independent
      of the ball size, the film thickness and the QDs concentration. For the PMMA-QDs
      nanocomposite films prepared from the same QDs concentration in chloroform, the
      thicker the PMMA-QDs nanocomposite film, the larger the wavelength for the same
      distance to the ball center. The effect of confinement of two steel balls on the
      surface patterns over the PMMA-QDs nanocomposite films is studied via a template
      of "two spheres on film". Symmetric surface patterns are formed. There exist two
      types of featureless zone between the two balls, depending on the distance
      between the two balls: one is the inner featureless zone and the other is the
      outer featureless zone. The size of both featureless zones increases with the
      increase of the ball distance.

PMID- 27714346
TI  - Structural behaviour and gene delivery in complexes formed between DNA and
      arginine-containing peptide amphiphiles.
AB  - We describe in depth the structure of complexes formed between DNA and two
      classes of arginine-containing peptide amphiphiles, namely, the lipopeptide PRW
      C16 (P = proline, R = arginine, W = tryptophan, C16 = C16 : 0 alkyl chain) and
      the bolaamphiphile RFL4FR (R = arginine, F = phenylalanine, L = leucine). A
      combination of X-ray and neutron scattering provided unprecedented insights into
      the local structure of these complexes. Lipopeptide-based complexes self
      assembled into layered structures with large-scale fractal features, hosting DNA
      in the interstices. Bola-amphiphile scaffolds were characterized by planar
      structures with DNA strands presumably sandwiched in-between peptide nanotapes.
      Importantly, complexation did not affect the structural integrity of DNA in
      either of the two complexes. The bolaamphiphile conjugates displayed high levels
      of molecular ordering in contrast to the liquid-crystalline features observed in
      lipopeptide assemblies. Peptide-DNA complexes were assessed for their potential
      as a means to deliver the reporter vector pEGFP-N1 into SW480 human colon
      carcinoma cells. Successfully transfected cells expressed green fluorescent
      protein. The potentiating effect of PRW-C16 on the cellular uptake of ectopic DNA
      was found to be much greater than that observed with RFL4FR. In contrast to the
      bolaamphiphile-based conjugate, the liquid-crystalline nature of the lipopeptide
      complex is likely to play a key role in DNA release and transfection efficiency
      since these weakly bound structures require lower energy expenditure during
      disassembly and load release.

PMID- 27714347
TI  - Correction: A systematic study of protein labeling by fluorogenic probes using
      cysteine targeting vinyl sulfone-cyclooctyne tags.
AB  - Correction for 'A systematic study of protein labeling by fluorogenic probes
      using cysteine targeting vinyl sulfone-cyclooctyne tags' by B. Soveges, et al.,
      Org. Biomol. Chem., 2016, 14, 6071-6078.

PMID- 27714348
TI  - Nanoparticle diffusion in crowded and confined media.
AB  - We identify distinct mechanisms controlling slowing of nanoparticle diffusion
      through complex media featuring both rigid geometrical confinement and soft
      mobile crowders. Towards this end, we use confocal microscopy and single particle
      tracking to probe the diffusion of 400 nm nanoparticles suspended in Newtonian
      water, in a Newtonian glycerol/water mixture, or in a non-Newtonian polymer
      solution through a model porous medium, a packed bed of microscale glass beads.
      The mobility of nanoparticles, as quantified by the long-time diffusion
      coefficient extracted from the particle mean-squared displacement, slows as the
      average pore size of the packed bed media decreases for both Newtonian and non
      Newtonian solutions. The distribution of particle displacements is non-Gaussian,
      consistent with the spatial heterogeneity of the geometrical confinement imposed
      by the packed bed. The slowing of nanoparticle mobility in all solutions follows
      the predictions of models that describe hydrodynamic interactions with the packed
      bed. In non-Newtonian solutions, depletion interactions due to the polymers near
      the glass beads result in temporary adsorption of particles onto the bead
      surface, as indicated by a stretched-exponential distribution of residence times.
      Our results therefore suggest that the confined diffusive dynamics of
      nanoparticles in polymer solutions is controlled by two competing mechanisms:
      hydrodynamic interactions between particles and spatial obstacles, which dictate
      the long-time slowing of diffusion, and depletion interactions between particles
      and confining walls due to the macromolecules, which control transient adsorption
      and hence alter the statistics of the short-time motion.

PMID- 27714349
TI  - Influence of chain topology on polymer crystallization: poly(ethylene oxide)
      (PEO) rings vs. linear chains.
AB  - The absence of entanglements, the more compact structure and the faster diffusion
      in melts of cyclic poly(ethylene oxide) (PEO) chains have consequences on their
      crystallization behavior at the lamellar and spherulitic length scales. Rings
      with molecular weight below the entanglement molecular weight (M < Me), attain
      the equilibrium configuration composed from twice-folded chains with a lamellar
      periodicity that is half of the corresponding linear chains. Rings with M > Me
      undergo distinct step-like conformational changes to a crystalline lamellar with
      the equilibrium configuration. Rings melt from this configuration in the absence
      of crystal thickening in sharp contrast to linear chains. In general, rings more
      easily attain their extended equilibrium configuration due to strained segments
      and the absence of entanglements. In addition, rings have a higher equilibrium
      melting temperature. At the level of the spherulitic superstructure, growth rates
      are much faster for rings reflecting the faster diffusion and more compact
      structure. With respect to the segmental dynamics in their semi-crystalline
      state, ring PEOs with a steepness index of ~34 form some of the "strongest"
      glasses.

PMID- 27714350
TI  - Tuning the bridging attraction between large hard particles by the softness of
      small microgels.
AB  - In this study, the attraction between large hard polystyrene (PS) spheres is
      studied by using three types of small microgels as bridging agents. One is a
      purely soft poly(N-isopropylacrylamide) (PNIPAM) microgel, the other two have a
      non-deformable PS hard core surrounded by a soft PNIPAM shell but are different
      in the core-shell ratio. The affinity for bridging the large PS spheres is
      provided and thus affected by the PNIPAM constituent in the microgels. The
      bridging effects caused by the microgels can be indirectly incorporated into
      their influence on the effective attraction interaction between the large hard
      spheres, since the size of the microgels is very small in comparison to the size
      of the PS hard spheres. At a given volume fraction of large PS spheres, they
      behave essentially as hard spheres in the absence of small microgels. By
      gradually adding the microgels, the large spheres are connected to each other
      through the bridging of small particles until the attraction strength reaches a
      maximum value, after which adding more small particles slowly decreases the
      effective attraction strength and eventually the large particles disperse
      individually when saturated adsorption is achieved. The aggregation and gelation
      behaviors triggered by these three types of small microgels are compared and
      discussed. A way to tune the strength and range of the short-range attractive
      potential via changing the softness of bridging microgels (which can be achieved
      either by using core-shell microgels or by changing the temperature) is proposed.

PMID- 27714351
TI  - Dynamic scaling of ferromagnetic micro-rod clusters under a weak magnetic field.
AB  - A controlled configurational change of micro-clusters in suspensions is essential
      for many smart material applications. In this paper, the dynamic process of
      ferromagnetic microrod clusters (FMRCs) under an external magnetic field was
      studied as a function of the cluster size N and the applied field B. The FMRCs
      rearranged from a side-by-side raft-like structure to an end-to-end chain-like
      structure, originating from coupled motions through the field-driven alignment of
      both ferromagnetic microrods and FMRCs. A theoretical model based on an extension
      of a zig-zag chain was developed, and both the cluster length and orientation
      could be characterized by a retardation time constant tau, with a relationship
      tau ~ N2/B, which agrees well with the experimental results, tau ~ N2.2+/
      0.2/B0.8+/-0.1. Such a model can be used to predict other cluster dynamics or the
      magneto-elastic behavior of other soft matters consisting of FMRCs.

PMID- 27714352
TI  - Weaving colloidal webs around droplets: spontaneous assembly of extended
      colloidal networks encasing microfluidic droplet ensembles.
AB  - The ability to form transient, self-assembling solid networks that 'cocoon'
      emulsion droplets on-demand allows new possibilities in the rapidly expanding
      area of microfluidic droplet-based materials science. In this communication, we
      demonstrate the spontaneous formation of extended colloidal networks that encase
      large microfluidic droplet ensembles, thus completely arresting droplet motion
      and effectively isolating each droplet from others in the ensemble. To do this,
      we employ molecular inclusion complexes of beta-cyclodextrin, which spontaneously
      form and assemble into colloidal solids at the droplet interface and beyond, via
      the outward diffusion of a guest molecule (dichloromethane) from the droplets. We
      illustrate the advantage of such transient network-based droplet stabilization in
      the area of pharmaceutical crystallization, where we are able to fabricate
      monodisperse spherical crystalline microgranules of 5-methyl-2-[(2
      nitrophenyl)amino]-3-thiophenecarbonitrile (ROY), a model hydrophobic drug, with
      a dramatic enhancement of particle properties compared to conventional methods.

PMID- 27714353
TI  - In situ study of photo- and thermo-induced color centers in photochromic rutile
      TiO2 in the temperature range 90-720 K.
AB  - This article reports an in situ UV-Vis-NIR diffuse reflectance (DR) spectroscopic
      and kinetic study of the photoformation and thermal annealing of light absorbing
      electronic point defects (color centers) in photochromic TiO2 in the temperature
      range 90-720 K using a simple laboratory-made cryostat-type accessory (for a Cary
      5000 spectrophotometer equipped with an integrating sphere). The accessory also
      allowed for UV-Vis-NIR DR studies to be undertaken either in vacuum or in an
      oxygen atmosphere at significantly high temperatures (to 720 K) to assess dark
      chemical events occurring in photochromic titania with the participation of color
      centers. The DR spectral and kinetic measurements provided the opportunity to
      examine the separation of photoinduced charge carriers at traps and thermally
      stimulated carrier detrapping and recombination, as well as the response of color
      centers to oxidative/reductive treatments of photochromic TiO2. Kinetic results
      also demonstrate the applicability of the fabricated DR accessory as a high
      temperature reaction cell in the systematic study of the principal regularities
      in the formation and destruction of color centers in titania at various
      temperatures and gaseous atmospheres.

PMID- 27714354
TI  - The surface tells it all: relationship between volume and surface fraction of
      liquid dispersions.
AB  - The properties of liquid dispersions, such as foams or emulsions, depend strongly
      on the volume fraction phi of the continuous phase. Concentrating on the example
      of foams, we show experimentally and theoretically that phi may be related to the
      fraction phis of the surface at a wall which is wetted by the continuous phase -
      given an expression for the interfacial energy or osmotic pressure of the bulk
      system. Since the surface fraction phis can be readily determined from optical
      measurement and since there are good general approximations available for
      interfacial energy and osmotic pressure we thus arrive at an advantageous method
      of estimating phi. The same relationship between phi and phis is also expected to
      provide a good approximation of the fraction of the bubble or drop surface which
      is wetted by the continuous phase. This is a parameter of great importance for
      the rheology and ageing of liquid dispersions.

PMID- 27714355
TI  - Bacterial swarmer cells in confinement: a mesoscale hydrodynamic simulation
      study.
AB  - A wide spectrum of Peritrichous bacteria undergo considerable physiological
      changes when they are inoculated onto nutrition-rich surfaces and exhibit a rapid
      and collective migration denoted as swarming. Thereby, the length of such swarmer
      cells and their number of flagella increases substantially. In this article, we
      investigated the properties of individual E. coli-type swarmer cells confined
      between two parallel walls via mesoscale hydrodynamic simulations, combining
      molecular dynamics simulations of the swarmer cell with the multiparticle
      particle collision dynamics approach for the embedding fluid. E. coli-type
      swarmer cells are three-times longer than their planktonic counter parts, but
      their flagella density is comparable. By varying the wall separation, we analyze
      the confinement effect on the flagella arrangement, on the distribution of cells
      in the gap between the walls, and on the cell dynamics. We find only a weak
      dependence of confinement on the bundle structure and dynamics. The distribution
      of cells in the gap changes from a geometry-dominated behavior for very narrow to
      fluid-dominated behavior for wider gaps, where cells are preferentially located
      in the gap center for narrower gaps and stay preferentially next to one of the
      walls for wider gaps. Dynamically, the cells exhibit a wide spectrum of migration
      behaviors, depending on their flagella bundle arrangement, and ranges from
      straight swimming to wall rolling.

PMID- 27714356
TI  - Geometrical instability in the imbibition of a sphere.
AB  - We study the imbibition of a spherical porous aggregate. When the difference in
      pressure between the inside and the outside of the aggregate is large enough, the
      imbibition front becomes unstable. This instability leads to the acceleration of
      the imbibition process. In more complex geometries with non-constant curvatures,
      the imbibition becomes locally unstable in the regions with the highest
      curvatures, leading to spatially heterogeneous front velocities.

PMID- 27714357
TI  - Enhanced photocatalytic degradation of phenol over anatase TiO2 in neutral water
      on addition of iron(iii) substituted polyoxotungstate.
AB  - PW12O40-type polyoxometalates have been widely used as electron mediators of TiO2
      photocatalysis for organic degradation in water, but they are stable only at pH 1
      2, which greatly limits their application for water treatment. Herein we report
      an iron(iii)-substituted PW11O39 (PW11Fe) capable of mediating the photocatalytic
      degradation of phenol and 2,4-dichlorophenol in an aerated aqueous suspension of
      anatase TiO2 at pH 2.0-7.2. As the initial concentration of PW11Fe or the initial
      pH of the suspension increased, the rate of phenol degradation increased, and
      then decreased. A maximum reaction rate was achieved at 2.0 mM PW11Fe and pH 5.5,
      which was 3.9 times higher than that measured without PW11Fe. In all cases, the
      rates of phenol degradation were of the first order in phenol, implying the
      recycling behavior of PW11Fe. Through electrochemical measurement, a possible
      mechanism is proposed, which involves the interfacial electron transfer from the
      irradiated TiO2 to PW11Fe, and the reduction of O2 by the reduced PW11Fe. This
      would improve the efficiency of the charge separation of TiO2, and consequently
      increase the rate of phenol degradation at interfaces.

PMID- 27714358
TI  - Segmental dynamics in lamellar phases of tapered copolymers.
AB  - Recent experiments have reported that the lamellar phase of salt-doped tapered
      copolymers exhibit higher ionic conductivity compared to those seen in similar
      morphologies of diblock copolymers. Such observations were in turn rationalized
      by invoking the corresponding glass transition temperature of the segregated
      copolymers. In this work we report the results of coarse-grained molecular
      dynamics simulations to identify the mechanisms underlying such characteristics.
      Explicitly, we probe the combined influences of the degree of segregation and the
      disparity in mobilities of the segments of the two blocks, upon the local
      relaxation dynamics of tapered copolymers segregated in lamellar phases. Our
      results show that the local dynamics of tapered copolymers depend on two
      independent factors, viz., the degree of segregation of such copolymers relative
      to their order-disorder transition temperature, and the relative mobilities
      (glass transition temperatures) of the two blocks. In qualitative correspondence
      with experiments, we find that for appropriate combinations of mobility ratios
      and degree of segregation, the lamellar phases of tapered copolymers can exhibit
      faster local segmental dynamics compared to diblock copolymers.

PMID- 27714359
TI  - Tracer diffusion in a sea of polymers with binding zones: mobile vs. frozen
      traps.
AB  - We use molecular dynamics simulations to investigate the tracer diffusion in a
      sea of polymers with specific binding zones for the tracer. These binding zones
      act as traps. Our simulations show that the tracer can undergo normal yet non
      Gaussian diffusion under certain circumstances, e.g., when the polymers with
      traps are frozen in space and the volume fraction and the binding strength of the
      traps are moderate. In this case, as the tracer moves, it experiences a
      heterogeneous environment and exhibits confined continuous time random walk
      (CTRW) like motion resulting in a non-Gaussian behavior. Also the long time
      dynamics becomes subdiffusive as the number or the binding strength of the traps
      increases. However, if the polymers are mobile then the tracer dynamics is
      Gaussian but could be normal or subdiffusive depending on the number and the
      binding strength of the traps. In addition, with increasing binding strength and
      number of polymer traps, the probability of the tracer being trapped increases.
      On the other hand, removing the binding zones does not result in trapping, even
      at comparatively high crowding. Our simulations also show that the trapping
      probability increases with the increasing size of the tracer and for a bigger
      tracer with the frozen polymer background the dynamics is only weakly non
      Gaussian but highly subdiffusive. Our observations are in the same spirit as
      found in many recent experiments on tracer diffusion in polymeric materials and
      question the validity of using Gaussian theory to describe diffusion in a crowded
      environment in general.

PMID- 27714360
TI  - Dendrimer assisted dispersion of carbon nanotubes: a molecular dynamics study.
AB  - Various unique physical, chemical, mechanical and electronic properties of carbon
      nanotubes (CNTs) make them very useful materials for diverse potential
      application in many fields. Experimentally synthesized CNTs are generally found
      in bundle geometry with a mixture of different chiralities and present a unique
      challenge to separate them. In this paper we have proposed the PAMAM dendrimer to
      be an ideal candidate for this separation. To estimate the efficiency of the
      dendrimer for the dispersion of CNTs from the bundle geometry, we have calculated
      potential of mean forces (PMF). Our PMF study of two dendrimer-wrapped CNTs shows
      lesser binding affinity compared to the two bare CNTs. PMF study shows that the
      binding affinity decreases for non-protonated dendrimer, and for the protonated
      case the interaction is fully repulsive in nature. For both the non-protonated as
      well as protonated cases, the PMF increases gradually with increasing dendrimer
      generations from 2 to 4 compared to the bare PMF. We have performed PMF
      calculations with (6,5) and (6,6) chirality to study the chirality dependence of
      PMF. Our study shows that the PMFs between two (6,5) and two (6,6) CNTs
      respectively are ~-29 kcal mol-1 and ~-27 kcal mol-1. Calculated PMF for
      protonated dendrimer-wrapped chiral CNTs is more compared to the protonated
      dendrimer-wrapped armchair CNTs for all the generations studied. However, for non
      protonated dendrimer-wrapped CNTs, such chirality dependence is not very
      prominent. Our study suggests that the dispersion efficiency of the protonated
      dendrimer is more compared to the non-protonated dendrimer and can be used as an
      effective dispersing agent for the dispersion of CNTs from the bundle geometry.

PMID- 27714361
TI  - Fracture toughness of hydrogels: measurement and interpretation.
AB  - The fracture mechanics of hydrogels, especially those with significantly enhanced
      toughness, has attracted extensive research interests. In this article we discuss
      the experimental measurement and theoretical interpretation of the fracture
      toughness for soft hydrogels. We first review the definition of fracture
      toughness for elastic materials, and the commonly used experimental
      configurations to measure it. In reality most gels are inelastic. For gels that
      are rate insensitive, we discuss how to interpret the fracture toughness
      associated with two distinct scenarios: crack initiation and steady-state crack
      propagation. A formulation to estimate energy dissipation during steady-state
      crack propagation is developed, and connections to previous models in the
      literature are made. For gels with rate-dependent behaviors, we review the
      physical mechanisms responsible for the rate-dependence, and outline the
      difficulties to rigorously define the fracture toughness for both crack
      initiation and propagation. We conclude by discussing a few fundamental questions
      on the fracture of tough gels that are yet to be answered.

PMID- 27714362
TI  - Solvent effects on the fracture of chemically crosslinked gels.
AB  - We have investigated how the fracture behavior of a polyacrylamide hydrogel is
      affected by different types of solvents poured into its crack tips. We obtained
      the following results: first, when water (good solvent or reaction solvent for
      the polyacrylamide gel) is poured, the fracture energy Gamma becomes smaller than
      that measured in air for small crack velocities V (V <= 10 mm s-1). Second, when
      good solvents other than water are poured, Gamma is enhanced for a large V region
      (5 <= V <= 60 mm s-1), but this effect is not observed for smaller V; Gamma(V) in
      good solvents converges to that in water as V -> 0. Third, when ethanol (poor
      solvent for polyacrylamide) is poured, stick-slip-like crack propagation appears
      in the entire V range, and Gamma calculated from the time-average of the
      oscillating tearing forces is larger than that in air or in other solvents. We
      discuss the results on the basis of diffusion dynamics around the crack tips of
      the gel.

PMID- 27714363
TI  - Programmable mechanical metamaterials: the role of geometry.
AB  - We experimentally and numerically study the role of geometry for the mechanics of
      biholar metamaterials, which are quasi-2D slabs of rubber patterned by circular
      holes of two alternating sizes. We recently showed how the response to uniaxial
      compression of these metamaterials can be programmed by lateral confinement. In
      particular, there is a range of confining strains epsilonx for which the
      resistance to compression becomes non-trivial-non-monotonic or hysteretic-in a
      range of compressive strains epsilony. Here we show how the dimensionless
      geometrical parameters t and chi, which characterize the wall thickness and size
      ratio of the holes that pattern these metamaterials, can significantly tune these
      ranges over a wide range. We study the behavior for the limiting cases where the
      wall thickness t and the size ratio chi become large, and discuss the new physics
      that arises there. Away from these extreme limits, the variation of the strain
      ranges of interest is smooth with porosity, but the variation with size ratio
      evidences a cross-over at low chi from biholar to monoholar (equal sized holes)
      behavior, related to the elastic instabilities in purely monoholar metamaterials.
      Our study provides precise guidelines for the rational design of programmable
      biholar metamaterials, tailored to specific applications, and indicates that the
      widest range of programmability arises for moderate values of both t and chi.

PMID- 27714364
TI  - Analysis of the aging effects on the viscoelasticity of alginate gels.
AB  - The effect of aging on the mechanical behaviour of ionically cross-linked
      alginate gels is studied in detail. Relaxation experiments upon both unconfined
      compression and torsion are performed on samples at different aging times. The
      elastic moduli of the gel are found to increase with the aging time, whereas the
      internal (constitutive) mechanism of the relaxation of the solid component of the
      gel is found to be unaffected by aging. It is demonstrated that the Linear Visco
      Elastic Stress/Diffusion Coupling model [D. Larobina, F. Greco, J. Chem. Phys.,
      2012, 136, 134904], recently developed by two of the present authors, is able to
      quantitatively reproduce the experimental data for differently aged samples, at
      early-to-intermediate relaxation times. Moreover, it is shown that the gel always
      undergoes a spontaneous expulsion of water (syneresis) and some spontaneous
      deformation for a sufficiently long observation time, even in the absence of any
      externally imposed strain. The latter phenomenology progressively slows down with
      increasing of the gel age. By proper time shifting of the late relaxation decays,
      i.e., by properly defining an "effective time", master curves can be obtained in
      all cases, with all data pertaining to differently aged samples collapsing on a
      single relaxation law for each deformation history. The dependence of the shift
      factors on the aging time is found to follow a power law behavior, with an
      exponent of 1.39.

PMID- 27714365
TI  - Mean-field beyond mean-field: the single particle view for moderately to strongly
      coupled charged fluids.
AB  - In a counter-ion only charged fluid, Coulomb coupling is quantified by a single
      dimensionless parameter. Yet, the theoretical treatment of moderately to strongly
      coupled charged fluids is a difficult task, central to the understanding of a
      wealth of soft matter problems, including biological systems. We show that the
      corresponding coupling regime can be remarkably well described by a single
      particle treatment, which, at variance with previous works, takes due account of
      inter-ionic interactions. To this end, the prototypical problem of a planar
      charged dielectric interface is worked out. Testing our predictions against Monte
      Carlo simulation data reveals an excellent agreement.

PMID- 27714366
TI  - A highly stretchable double-network composite.
AB  - Inspired by the toughening mechanism of double-network (DN) hydrogels, a soft
      composite consisting of a fabric mesh and VHB tape layers was fabricated. The
      composite was as stiff as the fabric mesh, and as stretchable as the VHB tape. At
      certain compositions, the composite was significantly stronger and tougher than
      the base materials. The extensibility and toughness of the composite can be
      attributed to a damage delocalization mechanism similar to that of the DN gels.
      In the partially damaged regions, the fabric mesh fragmented into small islands,
      surrounded by the highly stretched VHB tapes. Accommodated by the finite sliding
      at the interface, the large deformation of the composite is highly non-affine.
      Just as the DN gels, the coexistence of the partially damaged and intact regions
      resulted in a stable necking in the composite when subjected to uniaxial tension.
      The propagation of the necking zone corresponded to a plateau on the stress
      stretch curve. During cyclic loading, the composite also exhibited stress
      hysteresis with almost recoverable strain, similar to that in a DN gel. To
      rationalize these observations and to better understand the underlying physical
      mechanism, a simple 1D model has been developed for the damage evolution process
      in the composite. The predictions of the model have achieved good agreement with
      the measured properties of the composite of various compositions. Furthermore,
      the composite itself may also be regarded as a macroscopic model when studying
      the properties and toughening mechanism of the DN gels.

PMID- 27714367
TI  - Developing a self-healing supramolecular nucleoside hydrogel.
AB  - Low molecular weight gelator hydrogels provide a viable alternative to
      traditional polymer based drug delivery platforms, owing to their tunable
      stability and in most cases inherent biocompatibility. Here we report the first
      self-healing nucleoside hydrogel using N4-octanoyl-2'-deoxycytidine (0.5% w/v)
      for drug delivery. The hydrogel's cross-linked nanofibrillar structure, was
      characterised using oscillatory rheology and confirmed using SEM and TEM imaging.
      The potential of this gel for drug delivery was explored in vitro using
      fluorescently labelled tracers. Cell viability assays were conducted using
      pancreatic cell lines which tolerated the gels well; whilst no adverse effects on
      the viability or proliferation of cells were observed for fibroblast cell lines.

PMID- 27714368
TI  - Reorientation mechanisms of block copolymer/CdSe quantum dot composites under
      application of an electric field.
AB  - Time- and temperature-resolved in situ birefringence measurements were applied to
      analyze the effect of nanoparticles on the electric field-induced alignment of a
      microphase separated solution of poly(styrene)-block-poly(isoprene) in toluene.
      Through the incorporation of isoprene-confined CdSe quantum dots the
      reorientation behavior is altered. Particle loading lowers the order-disorder
      transition temperature, and increases the defect density, favoring nucleation and
      growth as an alignment mechanism over rotation of grains. The temperature
      dependent alteration in the reorientation mechanism is analyzed via a combination
      of birefringence and synchrotron SAXS. The detailed understanding of the effect
      of nanoparticles on the reorientation mechanism is an important prerequisite for
      optimization of electric-field-induced alignment of block copolymer/nanoparticle
      composites where the block copolymer guides the nanoparticle self-assembly into
      anisotropic structures.

PMID- 27714369
TI  - Thermo-responsive shape and optical memories of photonic composite films enabled
      by glassy liquid crystalline polymer networks.
AB  - We propose a novel shape and optical memories of a photonic composite film based
      on a silica opal photonic crystal (PC) template and a liquid crystal polymer
      network (LCN). Here, the photonic composite film was fabricated by introducing a
      LCN precursor into a silica opal PC template, followed by UV photo-polymerization
      and then by the removal of the template. The obtained bilayer-structure photonic
      film was found to spontaneously form a three-dimensional (3D) temporary bending
      shape in response to heating, and thus the corresponding reflection color of the
      photonic composite film shows a blue shift during bending deformation. The
      inherent mechanisms of these two observations could be attributed to the
      variations of the LC molecule orientation and the light reflection in the
      photonic composite film during the thermal process. More intriguingly, the
      resulting temporary bending shape was fixed by applying mechanical force during
      slowly cooling down to the room temperature or autonomously fixed by a rapid
      cooling in liquid nitrogen. Additionally, this temporary state could restore back
      to the permanent flat shape when the film is cooled from the heat source without
      an external force. Finally, more complex 3D shape-memory samples could also be
      achieved by simply controlling the LC alignment or designing the sample geometry.
      This work opens up a new way to develop a novel shape-memory polymer photonic
      film.

PMID- 27714370
TI  - Thermoosmotic microfluidics.
AB  - Microchannels with asymmetrically ratcheted walls are here shown to behave as
      effective and versatile microfluidic pumps if locally heated. When the boundary
      walls have different temperatures, the confined liquid experiences a temperature
      gradient along the sawtooth edges, which can induce a thermoosmotic flow. A
      mesoscale molecular simulation approach is here employed to investigate the flows
      which are contrasted using an analytical approach. Microchannels can be composed
      by one or two ratcheted walls which can be straight or cylindrical. Varying the
      channel geometry can not only change the overall fluid flux, but also vary the
      flow patters from shear to capillary type, or even to extensional type flows.
      This scheme does not require multiphase fluids or any movable channel parts,
      although they are possible to be implemented. The proposed principle is then very
      versatile to locally manipulate complex fluids, and a promising tool to recover
      waste heat, to facilitate cooling of microchips, and to manufacture portable lab
      on-a-chip devices.

PMID- 27714371
TI  - Controllable hierarchical self-assembly of gemini supra-amphiphiles: the effect
      of spacer length.
AB  - Gemini supra-amphiphiles with different spacer lengths, [M-n-M]2+@2[DBS]- (n = 2,
      6, 10), were easily constructed. The conformational flexibility and
      hydrophobicity of the spacer group can be effectively tailored through regulating
      the spacer length, leading to the fine control of the topologies and subsequent
      hierarchical self-assemblies of [M-n-M]2+@2[DBS]-. Vesicles are primarily
      fabricated by [M-n-M]2+@2[DBS]-, and then successively fused into vesicle
      clusters, nanotubes, and planar bilayers, whose bilayer curvatures are gradually
      decreased, with increasing spacer length. Coating [M-10-M]2+ with beta-CD can
      reduce the flexibility and hydrophobicity of the decyl spacer, resulting in the
      reversion from planar bilayers to vesicles. Furthermore, stable aqueous two-phase
      systems (ATPSs) that spontaneously formed via vesicle fusion in the solutions of
      [M-n-M]2+@2[DBS]- (n = 6, 10) can act as functional supramolecular systems in the
      isolation and purification of oil-soluble biomaterials.

PMID- 27714372
TI  - Electrokinetics of nanoparticle gel-electrophoresis.
AB  - Gel-electrophoresis has been demonstrated in recent decades to successfully sort
      a great variety of nanoparticles according to their size, charge, surface
      chemistry, and corona architecture. However, quantitative theoretical
      interpetations have been limited by the number and complexity of factors that
      influence particle migration. Theoretical models have been fragmented and
      incomplete with respect to their counterparts for free-solution electrophoresis.
      This paper unifies electrokinetic models that address complex nanoparticle corona
      architectures, corona and gel charge regulation (e.g., by the local pH), multi
      component electrolytes, and non-linear electrostatics and relaxation effects. By
      comprehensively addressing the electrokinetic aspects of the more general gel
      electrophoresis problem, in which short-ranged steric interactions are
      significant, a stage is set to better focus on the physicochemical and steric
      factors. In this manner, it is envisioned that noparticle gel-electrophoresis may
      eventually be advanced from a nanoparticle-characterization tool to one that
      explicitly probes the short-ranged interactions of nanoparticles with soft
      networks, such as synthetic gels and biological tissues. In this paper,
      calculations are undertaken that identify a generalized Huckel limit for
      nanoparticles in low-conductivity gels, and a new Smoluchowski limit for
      polyelectrolyte-coated particles in high-conductivity gels that is independent of
      the gel permeability. Also of fundamental interest is a finite, albeit small,
      electrophoretic mobility for uncharged particles in charged gels. Electrophoretic
      mobilities and drag coefficients (with electroviscous effects) for nanoparticles
      bearing non-uniform coronas show that relaxation effects are typically weak for
      the small nanoparticles (radius ~3-10 nm) to which gel-electrophoresis has
      customarily been applied, but are profound for the larger nanoparticles (radius ?
      40 nm in low conductivity gels) to which passivated gel-electrophoresis
      experiments have recently been applied. To demonstrate its practical application,
      the model is applied to (pH charge regulating) carboxylated polystyrene
      nanospheres in low-density passivated agarose gels (weak steric effects). This
      furnishes a new theoretical interpretation of literature data for which a finite
      diffuse-layer-thickness, pH-charge regulation, high charge, and relaxation
      effects dominate over the steric influences.

PMID- 27714373
TI  - Coarse-grained modeling of crystal growth and polymorphism of a model
      pharmaceutical molecule.
AB  - We describe a systematic coarse-graining method to study crystallization and
      predict possible polymorphs of small organic molecules. In this method, a coarse
      grained (CG) force field is obtained by inverse-Boltzmann iteration from the
      radial distribution function of atomistic simulations of the known crystal. With
      the force field obtained by this method, we show that CG simulations of the drug
      phenytoin predict growth of a crystalline slab from a melt of phenytoin, allowing
      determination of the fastest-growing surface, as well as giving the correct
      lattice parameters and crystal morphology. By applying meta-dynamics to the
      coarse-grained model, a new crystalline form of phenytoin (monoclinic, space
      group P21) was predicted which is different from the experimentally known crystal
      structure (orthorhombic, space group Pna21). Atomistic simulations and quantum
      calculations then showed the polymorph to be meta-stable at ambient temperature
      and pressure, and thermodynamically more stable than the conventional
      orthorhombic crystal at high pressure. The results suggest an efficient route to
      study crystal growth of small organic molecules that could also be useful for
      identification of possible polymorphs as well.

PMID- 27714374
TI  - Hydrodynamic oscillations and variable swimming speed in squirmers close to
      repulsive walls.
AB  - We present a lattice Boltzmann study of the hydrodynamics of a fully resolved
      squirmer, confined in a slab of fluid between two no-slip walls. We show that the
      coupling between hydrodynamics and short-range repulsive interactions between the
      swimmer and the surface can lead to hydrodynamic trapping of both pushers and
      pullers at the wall, and to hydrodynamic oscillations in the case of a pusher. We
      further show that a pusher moves significantly faster when close to a surface
      than in the bulk, whereas a puller undergoes a transition between fast motion and
      a dynamical standstill according to the range of the repulsive interaction. Our
      results critically require near-field hydrodynamics and demonstrate that far
      field hydrodynamics is insufficient to give even a qualitatively correct account
      of swimmer behaviour near walls. Finally our simulations suggest that it should
      be possible to control the density and speed of squirmers at a surface by tuning
      the range of steric and electrostatic swimmer-wall interactions.

PMID- 27714375
TI  - The architecture of the adsorbed layer at the substrate interface determines the
      glass transition of supported ultrathin polystyrene films.
AB  - To elucidate the mechanism underlying the effect of polymer/solid interfacial
      interactions on the dynamics of thin polymer films, the glass transition of thin
      end-functionalized polystyrene films supported on SiO2-Si, such as proton
      terminated PS (PS-H), alpha,omega-dicarboxy-terminated PS (PS-COOH), and
      alpha,omega-dihydroxyl-terminated PS (PS-OH), was investigated. All the PS films
      exhibited a substantial depression in Tg with decreasing film thickness, while
      the extent of such depression was strongly dependent on the chemical structure of
      the end groups and molecular weights. It was found that T - T of the various PS
      films increased linearly with increasing hads/Rg, in which hads is the thickness
      of the interfacial adsorbed layer and Rg is the radius of gyration of PS. The
      hads/Rg is a direct reflection of the macromolecular chain conformation within
      the adsorbed layer which was affected by its end groups and molecular weights.
      These findings are in line with the work of Napolitano, and present direct
      experimental evidence.

PMID- 27714376
TI  - Shape oscillations of particle-coated bubbles and directional particle expulsion.
AB  - Bubbles stabilised by colloidal particles can find applications in advanced
      materials, catalysis and drug delivery. For applications in controlled release,
      it is desirable to remove the particles from the interface in a programmable
      fashion. We have previously shown that ultrasound waves excite volumetric
      oscillations of particle-coated bubbles, resulting in precisely timed particle
      expulsion due to interface compression on a ultrafast timescale [Poulichet et
      al., Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 5932]. We also observed shape
      oscillations, which were found to drive directional particle expulsion from the
      antinodes of the non-spherical deformation. In this paper we investigate the
      mechanisms leading to directional particle expulsion during shape oscillations of
      particle-coated bubbles driven by ultrasound at 40 kHz. We perform high-speed
      visualisation of the interface shape and of the particle distribution during
      ultrafast deformation at a rate of up to 104 s-1. The mode of shape oscillations
      is found to not depend on the bubble size, in contrast with what has been
      reported for uncoated bubbles. A decomposition of the non-spherical shape in
      spatial Fourier modes reveals that the interplay of different modes determines
      the locations of particle expulsion. The n-fold symmetry of the dominant mode
      does not always lead to desorption from all 2n antinodes, but only those where
      there is favourable alignment with the sub-dominant modes. Desorption from the
      antinodes of the shape oscillations is due to different, concurrent mechanisms.
      The radial acceleration of the interface at the antinodes can be up to 105-106 ms
      2, hence there is a contribution from the inertia of the particles localised at
      the antinodes. In addition, we found that particles migrate to the antinodes of
      the shape oscillation, thereby enhancing the contribution from the surface
      pressure in the monolayer.

PMID- 27714377
TI  - Collective dynamics of chemically active particles trapped at a fluid interface.
AB  - Chemically active colloids generate changes in the chemical composition of their
      surrounding solution and thereby induce flows in the ambient fluid which affect
      their dynamical evolution. Here we study the many-body dynamics of a monolayer of
      spherically symmetric active particles trapped at a fluid-fluid interface. To
      this end we consider a model for the large-scale spatial distribution of
      particles which incorporates the direct pair interaction (including also the
      capillary interaction which is caused specifically by the interfacial trapping)
      as well as the effect of hydrodynamic interactions (including the Marangoni flow
      induced by the response of the interface to the chemical activity). The values of
      the relevant physical parameters for typical experimental realizations of such
      systems are estimated and various scenarios, which are predicted by our approach
      for the dynamics of the monolayer, are discussed. In particular, we show that the
      chemically-induced Marangoni flow can prevent the clustering instability driven
      by the capillary attraction.

PMID- 27714378
TI  - A new model for fluid velocity slip on a solid surface.
AB  - A general adsorption model is developed to describe the interactions between near
      wall fluid molecules and solid surfaces. This model serves as a framework for the
      theoretical modelling of boundary slip phenomena. Based on this adsorption model,
      a new general model for the slip velocity of fluids on solid surfaces is
      introduced. The slip boundary condition at a fluid-solid interface has hitherto
      been considered separately for gases and liquids. In this paper, we show that the
      slip velocity in both gases and liquids may originate from dynamical adsorption
      processes at the interface. A unified analytical model that is valid for both gas
      solid and liquid-solid slip boundary conditions is proposed based on surface
      science theory. The corroboration with the experimental data extracted from the
      literature shows that the proposed model provides an improved prediction compared
      to existing analytical models for gases at higher shear rates and close agreement
      for liquid-solid interfaces in general.

PMID- 27714379
TI  - Determination of equilibrium and rate constants for complex formation by
      fluorescence correlation spectroscopy supplemented by dynamic light scattering
      and Taylor dispersion analysis.
AB  - The equilibrium and rate constants of molecular complex formation are of great
      interest both in the field of chemistry and biology. Here, we use fluorescence
      correlation spectroscopy (FCS), supplemented by dynamic light scattering (DLS)
      and Taylor dispersion analysis (TDA), to study the complex formation in model
      systems of dye-micelle interactions. In our case, dyes rhodamine 110 and ATTO-488
      interact with three differently charged surfactant micelles: octaethylene glycol
      monododecyl ether C12E8 (neutral), cetyltrimethylammonium chloride CTAC
      (positive) and sodium dodecyl sulfate SDS (negative). To determine the rate
      constants for the dye-micelle complex formation we fit the experimental data
      obtained by FCS with a new form of the autocorrelation function, derived in the
      accompanying paper. Our results show that the association rate constants for the
      model systems are roughly two orders of magnitude smaller than those in the case
      of the diffusion-controlled limit. Because the complex stability is determined by
      the dissociation rate constant, a two-step reaction mechanism, including the
      diffusion-controlled and reaction-controlled rates, is used to explain the dye
      micelle interaction. In the limit of fast reaction, we apply FCS to determine the
      equilibrium constant from the effective diffusion coefficient of the fluorescent
      components. Depending on the value of the equilibrium constant, we distinguish
      three types of interaction in the studied systems: weak, intermediate and strong.
      The values of the equilibrium constant obtained from the FCS and TDA experiments
      are very close to each other, which supports the theoretical model used to
      interpret the FCS data.

PMID- 27714380
TI  - Concentration-induced planar-to-homeotropic anchoring transition of stiff ring
      polymers on hard walls.
AB  - We study the structure and interfacial ordering of stiff ring polymers close to
      repulsive walls. For this purpose, we employ an anisotropic effective model in
      which the rings are pictured as soft, penetrable discs [P. Poier, C. N. Likos, A.
      J. Moreno and R. Blaak, Macromolecules, 2015, 48, 4983]. We have studied this
      model in the bulk and in the presence of a wall, employing Density Functional
      Theory and computer simulations. While the Ornstein-Zernike equation in
      combination with the Hypernetted Chain Approximation gives results that are in
      quantitative agreement with computer simulations, a simple Mean Field
      approximation strongly overestimates the interaction between the effective
      particles in the bulk. We discover that by increasing density one can induce a
      reorientation of the effective rings in the vicinity of a wall, which prefer to
      orient themselves parallel to the surface (face-on or planar) for low densities
      rho and reorient orthogonal to the wall (edge-on or homeotropic) for higher
      values of rho. This transition in the surface-structure can be observed in both
      computer simulations, as well as in an appropriate density functional theory. We
      trace its physical origin in the penetrable character of the rings, which allows
      for a reduction of the surface tension contribution due to ring-ring interactions
      upon the emergence of homeotropic ordering on the wall and increasing the density
      of the system.

PMID- 27714381
TI  - Amphiphilic BODIPY derivatives: the solvophobic effect on their photophysical
      properties and bioimaging in living cells.
AB  - Three novel amphiphilic BODIPY derivatives were prepared and their photophysical
      properties in THF/water mixtures with varying fractions of water were
      investigated. BDP-1 could self-assemble into different vesicle architectures in
      aqueous solution, while BDP-2 and BDP-3 with more hydrophilic abilities formed
      spherical and worm-like micelles. The BODIPY derivatives could be absorbed by
      HeLa cells and showed no apparent toxicity during the course of the test. In
      particular, unlike traditional amines or morpholinyl functionalized lysosome
      fluorescent probes, BDP-1 nanovesicles without targeted groups exhibit red
      emission and show effective lysosome biological imaging. Co-staining experiments
      with lysosome specific trackers further confirmed the disassembly of BDP-1
      nanovesicles in lysosomes. This research provides a new avenue of using probes
      without targeting the structural unit to stain special organelles and shows
      potential applications in cell imaging fields.

PMID- 27714382
TI  - Preparation and attachment of liquid-infused porous supra-particles to liquid
      interfaces.
AB  - We prepared model porous composite supra-particles and investigated the effect of
      the initial infused fluid phase on their attachment at the liquid-fluid
      interface. We used a simple method for fabrication of millimetre-sized spherical
      porous supra-particles from much smaller monodisperse latex microparticles as
      building blocks by evaporation of a polystyrene sulphate latex suspension on a
      hot super-hydrophobic surface. We annealed the dried supra-particles at the
      polymer's glass transition temperature to fuse partially their latex particle
      building blocks. Spherical porous supra-particles were produced above 40 wt%
      initial concentration of the latex particles in the suspension, which had a rough
      surface, with a porous and amorphous structure. We controlled the supra-particle
      size by varying the initial volume of the latex suspension drop, the latex
      particle concentration and the drop evaporation temperature. This preparation
      technique allowed limited control over the porosity of the supra-particles by
      varying the initial concentration of the latex particle suspension, the rate of
      evaporation and the annealing temperature. We characterised the surface
      morphology and the inner structure of supra-particles by SEM imaging. We report
      for the first time results of an MRI study of supra-particles attached to an air
      water or an oil-water interface, which indicated that only the surface layer of
      the building block particles attaches to the liquid interface while the pore
      fluid was not displaced by the outer fluid. We observed that supra-particles
      infused with water had different wettability and attachment positions at the oil
      water interface compared with the same particles infused with oil. Similarly, the
      infusion of the porous supra-particles with water led to a different attachment
      at the air-water interface compared to the attachment of the same supra-particle
      when dry. The fundamental importance of this result is that the porous particles
      (or colloid particle agglomerates) may give an oil-in-water or water-in-oil
      Pickering emulsion depending on whether they are initially impregnated with oil
      or water. The results of this study are relevant for particle-stabilised
      emulsions and foams in a range of pharmaceutical, food and cosmetic formulations
      as well as ore flotation.

PMID- 27714383
TI  - Alcohol consumption: monitoring, regulation and impact on public health.

PMID- 27714384
TI  - The drinking habits of youth in NSW, Australia: latest data and influencing
      factors.
AB  - The New South Wales School Students Health Behaviours Survey (2014) reported a
      substantial reduction in students aged 12-17 years reporting that they had ever
      consumed alcohol, from 82.7% in 2005 to 65.1% in 2014. Similar downward trends
      are reported nationally and internationally. Although overall consumption is
      declining, national recommendations maintain that it is safest for young people
      to not drink at all; however, 17% of all young people in Australia consumed
      alcohol in the past 7 days, with 6% consuming at a significant risk of harm. The
      factors that influence young people's uptake of alcohol are complex, including
      biological and broader social factors. This paper identifies some of the diverse
      influences on young people's alcohol consumption, and policies and programs that
      support healthy behaviours.

PMID- 27714385
TI  - Estimating prevalence of drug and alcohol presentations to hospital emergency
      departments in NSW, Australia: impact of hospital consultation liaison services.
AB  - The impact of drug and alcohol misuse has been the subject of widespread media
      discussion in the past year, particularly in the context of restricted alcohol
      trading hours in an effort to reduce alcohol-fuelled violence. A recent study
      evaluating NSW Health's drug and alcohol consultation liaison (CL) services1
      demonstrates how pervasive drug and alcohol problems are, and the impact they
      have on the health system. This paper highlights how expanding CL services to
      fill current unmet need could deliver a range of benefits to patients and
      hospitals.

PMID- 27714386
TI  - The impact of alcohol pharmacotherapies on public health in Australia is limited
      by low prescribing rates.
AB  - Alcohol use disorders are among the most common and disabling problems in
      Australia. A number of pharmacotherapies available in Australia have been shown
      to be effective and are subsidised through the Australian Government's
      Pharmaceutical Benefits Scheme. The uptake of these medicines is poor, and the
      majority of those who start treatment do not complete the recommended course. Use
      of these medicines is significantly lower in regions that are disadvantaged or
      remote, and in patients who are younger. Taken together, these factors limit the
      potential benefit to population health from treatment of alcohol use disorders.
      Barriers to treatment have been identified at the level of the patient, the
      provider, the medicine and the healthcare system. An integrated strategy may be
      required to overcome these barriers.

PMID- 27714387
TI  - Impacts of changes to trading hours of liquor licences on alcohol-related harm: a
      systematic review 2005-2015.
AB  - BACKGROUND: Legislative limits on trading hours for licensed premises have a long
      history in Australia as a key policy approach to managing alcohol-related
      problems. In recent years, following substantial extensions to permitted hours of
      sale, there has been renewed attention to policies aimed at reducing late-night
      trading hours. Restrictions on on-premise alcohol sales have been implemented in
      Australia after 3.30 am in Newcastle, and after 3 am in Kings Cross and the
      Sydney central business district in New South Wales. In July 2016, similar
      restrictions were introduced state-wide after 2 am, or 3 am in 'safe night
      precincts', in Queensland. Similar policy changes have occurred internationally
      (e.g. in the UK and the Nordic countries) and there is a growing body of research
      examining the impacts of trading hour policies on alcohol-related harm. Although
      there has been a series of reviews of the research in this area, the most recent
      is now 5 years old and limited to studies published before March 2008. Objective
      and importance of study: To examine recent (2005-2015) research about the impact
      of changing the hours of sale of alcohol on alcohol-related harms. The ongoing
      public discussion about trading hours policy in Australia can benefit from an up
      to-date and comprehensive review of the research. METHODS: Systematic review of
      the literature that considered the impact of policies that extended or restricted
      trading hours. MEDLINE, Core Collection, PsychINFO and EMBASE databases were
      searched from January 2005 to December 2015. Articles were summarised
      descriptively, focusing on studies conducted in Australia and published since the
      previous reviews. RESULTS: The search identified 21 studies, including seven from
      Australia. There were 14 studies published since previous reviews. A series of
      robust, well-designed Australian studies demonstrate that reducing the hours
      during which on-premise alcohol outlets can sell alcohol late at night can
      substantially reduce rates of violence. The Australian studies are supported by a
      growing body of international research. CONCLUSION: The evidence of effectiveness
      is strong enough to consider restrictions on late trading hours for bars and
      hotels as a key approach to reducing late-night violence in Australia.

PMID- 27714388
TI  - Genetic feedback to reduce alcohol consumption in hospital outpatients with risky
      drinking: feasibility and acceptability.
AB  - OBJECTIVE: There have been no trials in healthcare settings of genetic
      susceptibility feedback in relation to alcohol consumption. The purpose of this
      study was to determine the feasibility and acceptability of conducting a full
      scale randomised trial estimating the effect of personalised genetic
      susceptibility feedback on alcohol consumption in hospital outpatients with risky
      drinking. METHODS: Outpatients >=18 years of age who reported drinking more than
      14 standard drinks in the past week or in a typical week were asked to provide a
      saliva sample for genetic testing. Genetic susceptibility feedback was posted to
      participants 6 months after recruitment. The co-primary outcomes were the
      proportion of participants who (i) provided a saliva sample that could be
      genotyped, and (ii) spoke with a genetic counsellor. Secondary outcomes included
      changes in patients' weekly alcohol consumption; scores on scales measuring
      readiness to change, importance of changing and confidence in ability to change
      drinking habits; knowledge about which cancers are alcohol-attributable; and
      acceptability of the saliva collection procedure and the genetic-feedback
      intervention. McNemar's test and paired t-tests were used to test for differences
      between baseline and follow-up in proportions and means, respectively. RESULTS:
      Of 100 participants who provided a saliva sample, 93 had adequate DNA for at
      least one genotyping assay. Three participants spoke to a genetic counsellor.
      Patients' readiness to change their drinking, their views on the importance of
      changing and their stated confidence in their ability to change increased between
      baseline and follow-up. There was no increase in patients' knowledge about
      alcohol-attributable cancers nor any reduction in how much alcohol they drank 4
      months after receiving the feedback. Most participants (80%) were somewhat
      comfortable or very comfortable with the process used to collect saliva, 84%
      understood the genetic feedback, 54% found it useful, 10% had sought support to
      reduce their drinking after receiving the feedback, and 37% reported that the
      feedback would affect how much they drink in the future. CONCLUSION: Results of
      this study suggest it would be feasible to conduct a methodologically robust
      trial estimating the effect of genetic susceptibility feedback on alcohol
      consumption in hospital outpatients with risky drinking.

PMID- 27714389
TI  - Mesothelioma trends in the ACT and comparisons with the rest of Australia.
AB  - OBJECTIVES: Inhalation of asbestos fibres is the predominant cause of malignant
      mesothelioma. Domestic exposure to asbestos is a major community concern in the
      Australian Capital Territory (ACT) because of loose-fill asbestos home
      insulation. Little is known about how trends in mesothelioma rates in the ACT
      compare with those elsewhere. The objective of this study was to describe trends
      in mesothelioma rates in the ACT and compare them with those for the rest of
      Australia. METHODS: We used de-identified data from the ACT Cancer Registry (1982
      2014), and the Western Australia (WA) Cancer Registry and the Australian Cancer
      Database (1982-2011). We calculated crude mesothelioma rates, by 3-year periods,
      for the ACT and for the rest of Australia (excluding WA). We used Poisson
      regression to analyse mesothelioma trends from 1994 to 2011 (complete reporting
      period) using an indirect standardisation approach to adjust for age and sex.
      RESULTS: There were 140 mesothelioma cases reported to the ACT Cancer Registry
      between 1982 and 2014 - 81% male and 19% female. Between 1994 and 2011, age- and
      sex-adjusted mesothelioma rates in the ACT increased over time, on average by 12%
      per 3-year period (relative risk [RR] 1.12; 95% confidence interval [CI] 0.99,
      1.26). Compared with the rest of Australia (excluding WA), ACT rates were, on
      average, lower (RR 0.84; 95% CI 0.69, 1.02), but they increased at a higher rate
      (RR 1.12 per 3-year period; 95% CI 0.99, 1.27). These results are strongly
      influenced by the higher rate of mesothelioma observed in the ACT in 2009-2011,
      when ACT rates became similar to those for the rest of Australia (excluding WA).
      CONCLUSIONS: Although mesothelioma rates may have increased more in the ACT than
      the rest of Australia (excluding WA) during the past two decades, there is
      considerable uncertainty in the trends. More information is needed regarding the
      health risks associated with living in a house with loose-fill asbestos
      insulation. This is the subject of further studies within the ACT Asbestos Health
      Study.

PMID- 27714390
TI  - Developing a new Get Healthy Service program on reducing risky alcohol
      consumption.
AB  - Risky alcohol use has significant individual health and social impacts, and is
      related to short- and long-term harm, including injuries, accidents, liver
      diseases, some cancers, cardiovascular diseases and alcohol dependence. The Get
      Healthy Information & Coaching Service (GHS) is a free telephone coaching service
      supporting adults 16 years or older to reduce weight, improve nutrition and
      increase physical activity. Tailored programs are available for Aboriginal
      people, pregnant women and people at risk of type 2 diabetes. The GHS provides an
      opportunity to implement a specific program for participants wishing to reduce or
      cease their alcohol consumption. This paper describes the processes used to
      develop an Alcohol Program for the GHS. It outlines the contributions from
      clinical and program experts, the evidence base for the program's development,
      clinical screening tools, training for health coaches and referral processes for
      participants. The Alcohol Program has the potential to provide effective coaching
      to adults to voluntarily reduce short- and long-term risky alcohol consumption.

PMID- 27714391
TI  - Development of a multiple risk factor Brief Health Check for workplaces.
AB  - Health promotion in workplace settings has been prioritised to reduce chronic
      disease risk factors, both in Australia and internationally. This paper describes
      the design of a health risk assessment tool, the Brief Health Check (BHC). The
      BHC is one of two components of Get Healthy at Work, a state government-funded
      health promotion program for New South Wales workplaces. Policy imperatives
      required scaled-up delivery in the absence of a full pre-implementation summative
      evaluation. Translational formative evaluation was adapted to design an evidence
      based health risk assessment tool, a process for referring workers to healthy
      lifestyle programs, and a process for general practitioners to help workers
      mitigate their risk of chronic disease, independently of the workplace. The tool
      had good feasibility and acceptance, but barriers included business
      organisational issues (including the time taken to facilitate the health checks)
      and some scepticism among workers about the motivation of businesses and the
      absence of measurements other than waist circumference. A cluster nonrandomised
      trial showed no benefit of a modest incentive for participation. A significant
      proportion of workers were identified as being at risk of chronic disease, and
      many received an appropriate referral to an evidence based program. More work to
      improve uptake of referrals will increase the public health impact of the BHC.

PMID- 27714392
TI  - Public health advocacy in action: the case of unproven breast cancer screening in
      Australia.
AB  - In recent years, nonmammographic breast imaging devices, such as thermography,
      electrical impedance scanning and elastography, have been promoted directly to
      consumers, which has captured the attention of governments, researchers and
      health organisations. These devices are not supported by evidence and risk
      undermining existing mammographic breast cancer screening services. During a 5
      year period, Cancer Council Western Australia (CCWA) used strategic research
      combined with legal, policy and media advocacy to contest claims that these
      devices were proven alternatives to mammography for breast cancer screening. The
      campaign was successful because it had input from people with public health,
      academic, clinical and legal backgrounds, and took advantage of existing legal
      and regulatory avenues. CCWA's experience provides a useful advocacy model for
      public health practitioners who are concerned about unsafe consumer products,
      unproven medical devices, and misleading health information and advertising.

PMID- 27714393
TI  - Sporting clubs to tackle illegal drug use.

PMID- 27714394
TI  - Applications due to open soon for medical homes trial.

PMID- 27714395
TI  - No safe level: public health message targets moderate drinkers.

PMID- 27714396
TI  - Challenges and Opportunities for Harmonizing Research Methodology: Raw
      Accelerometry.
AB  - OBJECTIVES: Raw accelerometry is increasingly being used in physical activity
      research, but diversity in sensor design, attachment and signal processing
      challenges the comparability of research results. Therefore, efforts are needed
      to harmonize the methodology. In this article we reflect on how increased
      methodological harmonization may be achieved. METHODS: The authors of this work
      convened for a two-day workshop (March 2014) themed on methodological
      harmonization of raw accelerometry. The discussions at the workshop were used as
      a basis for this review. RESULTS: Key stakeholders were identified as
      manufacturers, method developers, method users (application), publishers, and
      funders. To facilitate methodological harmonization in raw accelerometry the
      following action points were proposed: i) Manufacturers are encouraged to provide
      a detailed specification of their sensors, ii) Each fundamental step of
      algorithms for processing raw accelerometer data should be documented, and
      ideally also motivated, to facilitate interpretation and discussion, iii)
      Algorithm developers and method users should be open about uncertainties in the
      description of data and the uncertainty of the inference itself, iv) All new
      algorithms which are pitched as "ready for implementation" should be shared with
      the community to facilitate replication and ongoing evaluation by independent
      groups, and v) A dynamic interaction between method stakeholders should be
      encouraged to facilitate a well-informed harmonization process. CONCLUSIONS: The
      workshop led to the identification of a number of opportunities for harmonizing
      methodological practice. The discussion as well as the practical checklists
      proposed in this review should provide guidance for stakeholders on how to
      contribute to increased harmonization.

PMID- 27714397
TI  - Comparing Graphical Formats for Feedback of Clinical Practice Data. A Multicenter
      Study among Anesthesiologists in France.
AB  - OBJECTIVES: Although graphical formats used to feedback clinical practice data
      may have an important impact, the most effective formats remain unknown. Using
      prevention of postoperative nausea and vomiting by anesthesiologists as an
      application, the objective of this study was to assess which graphical formats
      for feedback of clinical practice data are the most incentive to change practice.
      METHODS: We conducted a multicenter cross-sectional study among anesthesiologists
      randomized in two groups between March and June 2014. Each anesthesiologist
      assessed 15 graphical formats displaying an indicator of either prescription
      conformity or prescription effectiveness. Graphical formats varied by: type of
      graph (bar charts, linear sliders, or pictographs), presence or not of a target
      to reach, presence or not of a contrast between a hypothetical physician and his
      / her team, direction of the difference between the physician and his / her team,
      and restitution or not of the quality indicator evolution over the previous six
      months. The primary outcome was a numerical scale score expressing the
      anesthesiologists' motivation to change his / her practice (ranging from 1 to 10
      points). A linear mixed model was fitted to explain variation in motivation.
      RESULTS: Sixty-six anesthesiologists assessed the conformity indicator and 67
      assessed the effectiveness indicator. Factors associated with an increased
      motivation to change practice were: (i) presence of a clearly defined target to
      reach (conformity: beta = 0.24 points, p = 0.0046; effectiveness: beta = 1.11
      points, p < 0.0001); (ii) contrast between the physician and his / her team
      (conformity: beta = 0.38 points, p < 0.0001; effectiveness: beta = 0.33 points, p
      = 0.0021); (iii) better results for the team than for the physician (conformity:
      beta = 0.65 points, p < 0.0001; effectiveness beta = 1.16 points, p < 0.0001).
      For the effectiveness indicator, anesthesiologists were more motivated to change
      practice with bar charts (beta = 0.24 points, p = 0.0447) and pictographs (beta =
      0.45 points, p = 0.0001) than with linear sliders. CONCLUSIONS: Graphs associated
      with a defined target to reach should be preferred to deliver feedback,
      especially bar graphs or pictographs for indicators which are more complex to
      represent such as effectiveness indicators. Anesthesiologists are also more
      motivated to change practice when graphs report contrasted data between the
      physician and his / her team and a lower conformity or effectiveness for the
      physician than for his / her team.

PMID- 27714398
TI  - Seasonal influenza in octogenarians and nonagenarians admitted to a general
      hospital: epidemiology, clinical presentation and prognostic factors.
AB  - OBJECTIVE: Seasonal influenza is responsible for high annual morbidity and
      mortality worldwide, especially in elderly patients. The aim of the study was to
      analyse the epidemiological, clinical and prognostic features of influenza in
      octogenarians and nonagenarians admitted to a general hospital, as well as risk
      factors associated with mortality. METHODS: Retrospective, cross-sectional,
      descriptive study in patients admitted and diagnosed with influenza by molecular
      biology in the General University Hospital of Alicante from 1 January to 31 April
      2015. RESULTS: A total of 219 patients were diagnosed with influenza in the study
      period: 55 (25.1%) were <=64 years-old; 77 (35.2%) were aged 65-79; 67 (30.6%)
      were aged 80-89 years; and 20 (9.1%) were aged >=90 years. Most flu episodes were
      caused by influenza A (n=181, 82.6%). Patients aged 80 years or older had lower
      glomerular filtration rate (mean: 49.7 mL/min vs. 62.2 mL/min; p=0.006), a
      greater need for non-invasive mechanical ventilation (22% vs 9.3%; p=0.02),
      greater co-morbidity due to cardiac insufficiency (40.5% vs. 16.4%; p<0.001) and
      chronic renal disease (32.9 vs. 20%, p=0.03), and greater mortality (19% vs.
      2.9%; p<0.001). In a multivariate analysis, mortality was higher in those aged 80
      or over (adjusted odds ratio [ORa] 9.2, 95% confidence interval [CI] 1.65-51.1),
      those who had acquired the flu in a long-term care facility (ORa 11.9, 95% CI
      1.06-134), and those with hyperlactataemia (ORa 1.89, 95% CI 1.20-3.00).
      CONCLUSIONS: Seasonal influenza is a serious problem leading to elevated
      mortality in octogenarian and nonagenarian patients admitted to a general
      hospital.

PMID- 27714399
TI  - [Demographic and clinical features of diagnosed individuals of enterobiasis in
      the southern Gran Canaria: sampling assessment].
AB  - OBJECTIVE: Enterobius vermicularis, also known as pinworn, is the responsible
      agent for Human Enterobiasis. It is one of the most prevalent, but underrated,
      parasitic disease in children population. Diagnosis involves demonstration of
      either eggs or adult worms by Graham test. The aim of this study is to describe
      the clinical, demographic and microbiological features of patients with suspected
      diagnosis of Enterobiasis in southern Gran Canaria. METHODS: Descriptive and
      prospective study of perianal samples evaluated by Graham test in the
      Microbiology Department of 'Insular de Gran Canaria' University Hospital between
      November 2014 and November 2015. Descriptive analysis to evaluate the correlation
      between clinical and demographic variables and the results of Graham test
      microbiological observation. RESULTS: 1,128 samples were analyzed. E.
      vermicularis was found in 11.4% of the samples. Among the positives samples,
      88.4% belonged to children under 14 years, and 53.5% were male. Abdominal pain
      (18.6%), anal itching (11.6%), eosinophilia (8.5%) and intestinal parasitosis
      suspicion (7.8%) were the reasons of parasitological investigation request in
      positive samples. Nevertheless, a high proportion of the requests was not founded
      in a suspicious diagnosis or was unrelated to Enterobiasis. CONCLUSIONS:
      Enterobiasis is a common disease in primary health care and is of great
      importance in Gran Canaria. Quality in sample collection as well as diagnosis
      suspicious information are necessary for a good microbiological analysis.

PMID- 27714400
TI  - [Technical assist devices : Perspectives and new developments].
AB  - The development of technical assist devices in the context of cardiopulmonary
      resuscitation (CPR) reaches back to the early roots of modern resuscitation
      research. This article covers the subjects of extracorporeal CPR (ECPR),
      including extracorporeal life support (ECLS), emergency ECLS (EECLS) and
      mechanical resuscitation devices. Specifically, the potential use of active
      compression-decompression CPR (ACD-CPR), impedance threshold devices (ITD) and
      capnography as additional measures during resuscitation are described in detail.
      Furthermore, the article presents a compact preview of the potential future
      developments of technical aids in the field of life support and postresuscitation
      care.

PMID- 27714401
TI  - Consulting clinical pharmacologist about treatment of inpatients in a tertiary
      hospital in Serbia.

PMID- 27714402
TI  - Optimization of LC-Orbitrap-HRMS acquisition and MZmine 2 data processing for
      nontarget screening of environmental samples using design of experiments.
AB  - Liquid chromatography-high resolution mass spectrometry (LC-HRMS) is a well
      established technique for nontarget screening of contaminants in complex
      environmental samples. Automatic peak detection is essential, but its performance
      has only rarely been assessed and optimized so far. With the aim to fill this
      gap, we used pristine water extracts spiked with 78 contaminants as a test case
      to evaluate and optimize chromatogram and spectral data processing. To assess
      whether data acquisition strategies have a significant impact on peak detection,
      three values of MS cycle time (CT) of an LTQ Orbitrap instrument were tested.
      Furthermore, the key parameter settings of the data processing software MZmine 2
      were optimized to detect the maximum number of target peaks from the samples by
      the design of experiments (DoE) approach and compared to a manual evaluation. The
      results indicate that short CT significantly improves the quality of automatic
      peak detection, which means that full scan acquisition without additional MS2
      experiments is suggested for nontarget screening. MZmine 2 detected 75-100 % of
      the peaks compared to manual peak detection at an intensity level of 105 in a
      validation dataset on both spiked and real water samples under optimal parameter
      settings. Finally, we provide an optimization workflow of MZmine 2 for LC-HRMS
      data processing that is applicable for environmental samples for nontarget
      screening. The results also show that the DoE approach is useful and effort
      saving for optimizing data processing parameters. Graphical Abstract ?.

PMID- 27714403
TI  - Responses of the Antioxidant and Osmoregulation Systems of Fish Erythrocyte
      Following Copper Exposures in Differing Calcium Levels.
AB  - Freshwater fish Oreochromis niloticus were exposed to Cu in differing Ca2+ levels
      (15, 30 and 90 mg/L), using acute (0.3 uM, 3 d) and chronic (0.03 uM, 30 d)
      exposure protocols and enzyme activities related to the antioxidant (catalase,
      CAT, EC 1.11.1.6; superoxide dismutase, SOD, EC 1.15.1.1; glutathione peroxidase,
      GPx, EC 1.11.1.9) and osmoregulation (Total, Na+/K+-ATPase, EC 3.6.3.9, Mg2+
      ATPase, EC 3.6.3.2) systems in the erythrocytes were measured. Activities of
      antioxidant enzymes generally decreased significantly following either Ca2+ alone
      or Ca2++Cu combinations in both acute and chronic exposures. Na+/K+-ATPase
      activity significantly decreased in chronic exposures, though there was no clear
      trend in acute exposures. Mg2+-ATPase activity increased significantly in acute
      exposures, but not in chronic ones. There were more significant alterations in
      acute exposure compared to chronic ones. There was no clear trend regarding Cu
      toxicity and its relationship with Ca2+, which may possibly be prompted by the
      compensatory mechanisms of the enzymes. It may be concluded that freshwater fish
      erythrocytes may face different degrees of more physiological stress from
      different waters.

PMID- 27714404
TI  - The influence of motor imagery on the learning of a fine hand motor skill.
AB  - Motor imagery has been argued to affect the acquisition of motor skills. The
      present study examined the specificity of motor imagery on the learning of a fine
      hand motor skill by employing a modified discrete sequence production task: the
      Go/NoGo DSP task. After an informative cue, a response sequence had either to be
      executed, imagined, or withheld. To establish learning effects, the experiment
      was divided into a practice phase and a test phase. In the latter phase, we
      compared mean response times and accuracy during the execution of unfamiliar
      sequences, familiar imagined sequences, and familiar executed sequences. The
      electroencephalogram was measured in the practice phase to compare activity
      between motor imagery, motor execution, and a control condition in which
      responses should be withheld. Event-related potentials (ERPs) and event-related
      lateralizations (ERLs) showed strong similarities above cortical motor areas on
      trials requiring motor imagery and motor execution, while a major difference was
      found with trials on which the response sequence should be withheld. Behavioral
      results from the test phase showed that response times and accuracy improved
      after physical and mental practice relative to unfamiliar sequences (so-called
      sequence-specific learning effects), although the effect of motor learning by
      motor imagery was smaller than the effect of physical practice. These findings
      confirm that motor imagery also resembles motor execution in the case of a fine
      hand motor skill.

PMID- 27714406
TI  - You neglected a few.

PMID- 27714405
TI  - Lung-brain cross talk in the critically ill.

PMID- 27714407
TI  - Challenges with PRONE ventilation in ARDS patients: response to comments by
      Chertoff.

PMID- 27714408
TI  - Single cell biology beyond the era of antibodies: relevance, challenges, and
      promises in biomedical research.
AB  - Research of the past two decades has proved the relevance of single cell biology
      in basic research and translational medicine. Successful detection and isolation
      of specific subsets is the key to understand their functional heterogeneity.
      Antibodies are conventionally used for this purpose, but their relevance in
      certain contexts is limited. In this review, we discuss some of these contexts,
      posing bottle neck for different fields of biology including biomedical research.
      With the advancement of chemistry, several methods have been introduced to
      overcome these problems. Even though microfluidics and microraft array are newer
      techniques exploited for single cell biology, fluorescence-activated cell sorting
      (FACS) remains the gold standard technique for isolation of cells for many
      biomedical applications, like stem cell therapy. Here, we present a comprehensive
      and comparative account of some of the probes that are useful in FACS. Further,
      we illustrate how these techniques could be applied in biomedical research. It is
      postulated that intracellular molecular markers like nucleostemin (GNL3),
      alkaline phosphatase (ALPL) and HIRA can be used for improving the outcome of
      cardiac as well as bone regeneration. Another field that could utilize
      intracellular markers is diagnostics, and we propose the use of specific peptide
      nucleic acid probes (PNPs) against certain miRNAs for cancer surgical margin
      prediction. The newer techniques for single cell biology, based on intracellular
      molecules, will immensely enhance the repertoire of possible markers for the
      isolation of cell types useful in biomedical research.

PMID- 27714409
TI  - Filamentous actin accumulates during plant cell penetration and cell wall plug
      formation in Phytophthora infestans.
AB  - The oomycete Phytophthora infestans is the cause of late blight in potato and
      tomato. It is a devastating pathogen and there is an urgent need to design
      alternative strategies to control the disease. To find novel potential drug
      targets, we used Lifeact-eGFP expressing P. infestans for high resolution live
      cell imaging of the actin cytoskeleton in various developmental stages.
      Previously, we identified actin plaques as structures that are unique for
      oomycetes. Here we describe two additional novel actin configurations; one
      associated with plug deposition in germ tubes and the other with appressoria,
      infection structures formed prior to host cell penetration. Plugs are composed of
      cell wall material that is deposited in hyphae emerging from cysts to seal off
      the cytoplasm-depleted base after cytoplasm retraction towards the growing tip.
      Preceding plug formation there was a typical local actin accumulation and during
      plug deposition actin remained associated with the leading edge. In appressoria,
      formed either on an artificial surface or upon contact with plant cells, we
      observed a novel aster-like actin configuration that was localized at the contact
      point with the surface. Our findings strongly suggest a role for the actin
      cytoskeleton in plug formation and plant cell penetration.

PMID- 27714410
TI  - Role of CFTR in epithelial physiology.
AB  - Salt and fluid absorption and secretion are two processes that are fundamental to
      epithelial function and whole body fluid homeostasis, and as such are tightly
      regulated in epithelial tissues. The CFTR anion channel plays a major role in
      regulating both secretion and absorption in a diverse range of epithelial
      tissues, including the airways, the GI and reproductive tracts, sweat and
      salivary glands. It is not surprising then that defects in CFTR function are
      linked to disease, including life-threatening secretory diarrhoeas, such as
      cholera, as well as the inherited disease, cystic fibrosis (CF), one of the most
      common life-limiting genetic diseases in Caucasian populations. More recently,
      CFTR dysfunction has also been implicated in the pathogenesis of acute
      pancreatitis, chronic obstructive pulmonary disease (COPD), and the hyper
      responsiveness in asthma, underscoring its fundamental role in whole body health
      and disease. CFTR regulates many mechanisms in epithelial physiology, such as
      maintaining epithelial surface hydration and regulating luminal pH. Indeed,
      recent studies have identified luminal pH as an important arbiter of epithelial
      barrier function and innate defence, particularly in the airways and GI tract. In
      this chapter, we will illustrate the different operational roles of CFTR in
      epithelial function by describing its characteristics in three different tissues:
      the airways, the pancreas, and the sweat gland.

PMID- 27714412
TI  - Ecology and sampling techniques of an understudied subterranean habitat: the
      Milieu Souterrain Superficiel (MSS).
AB  - The term Milieu Souterrain Superficiel (MSS) has been used since the early 1980s
      in subterranean biology to categorize an array of different hypogean habitats. In
      general terms, a MSS habitat represents the underground network of empty air
      filled voids and cracks developing within multiple layers of rock fragments. Its
      origins can be diverse and is generally covered by topsoil. The MSS habitat is
      often connected both with the deep hypogean domain-caves and deep rock cracks-and
      the superficial soil horizon. A MSS is usually characterized by peculiar
      microclimatic conditions, and it can harbor specialized hypogean, endogean, and
      surface-dwelling species. In light of the many interpretations given by different
      authors, we reviewed 235 papers regarding the MSS in order to provide a state-of
      the-art description of these habitats and facilitate their study. We have briefly
      described the different types of MSS mentioned in the scientific literature
      (alluvial, bedrock, colluvial, volcanic, and other types) and synthesized the
      advances in the study of the physical and ecological factors affecting this
      habitat-i.e., microclimate, energy flows, animal communities, and trophic
      interactions. We finally described and reviewed the available sampling methods
      used to investigate MSS fauna.

PMID- 27714411
TI  - How cardiomyocytes sense pathophysiological stresses for cardiac remodeling.
AB  - In the past decades, the cardiovascular community has laid out the fundamental
      signaling cascades that become awry in the cardiomyocyte during the process of
      pathologic cardiac remodeling. These pathways are initiated at the cell membrane
      and work their way to the nucleus to mediate gene expression. Complexity is
      multiplied as the cardiomyocyte is subjected to cross talk with other cells as
      well as a barrage of extracellular stimuli and mechanical stresses. In this
      review, we summarize the signaling cascades that play key roles in cardiac
      function and then we proceed to describe emerging concepts of how the
      cardiomyocyte senses the mechanical and environmental stimuli to transition to
      the deleterious genetic program that defines pathologic cardiac remodeling. As a
      highlighting example of these processes, we illustrate the transition from a
      compensated hypertrophied myocardium to a decompensated failing myocardium, which
      is clinically manifested as decompensated heart failure.

PMID- 27714413
TI  - [Adjuvant study of high-risk muscle invasive urothelial carcinoma : Open-label,
      multicenter, randomized phase III study with atezolizumab (anti-PD-L1 antibody)
      as adjuvant therapy compared with observation in patients with high-risk muscle
      invasive urothelial carcinoma after surgical resection (IMvigor010)- study AB
      53/15 of the AUO].

PMID- 27714414
TI  - [Long-term outcome after endoscopic enucleation of the prostate : From monopolar
      enucleation to HoLEP and from HoLEP to EEP].
AB  - BACKGROUND: In the last 20 years various transurethral endoscopic enucleation
      techniques (EEP) have been established as a substitute for open prostatectomy
      (OP) and TURP. Since the 2016 update of the "EAU Guidelines on Management of Non
      Neurogenic Male Lower Urinary Tract Symptoms (LUTS), including Benign Prostatic
      Obstruction (BPO)", Holmium laser enucleation of the prostate (HoLEP) and bipolar
      enucleation being summarized as anatomical enucleating techniques are proposed as
      first choice for the surgical management of BPO of large volume prostates.
      OBJECTIVES: The purpose of this review is to demonstrate the available data on
      long-term outcomes of current EEP techniques. MATERIALS AND METHODS:
      PubMed/Medline and Scopus were searched using the terms: long term, HoLEP,
      ThuLEP, ThuVEP, DiLEP, ELEP, GreenlEP, Greenlight enucleation, bipolar
      enucleation, plasmakinetic enucleation, monopolar enucleation, and transurethral
      enucleation. Studies with a follow-up >=48 months were selected. RESULTS: In all,
      5 randomized controlled trials (2 HoLEP, 2 bipolar enucleation, 1 Thulium laser
      resection of the prostate in tangerine technique [TmLR-TT]), 3 prospective cohort
      studies (2 thulium vapoenucleation [ThuVEP], 1 TmLRP-TT), and 2 retrospective
      studies with large patient cohorts were selected. All EEP were equivalent to OP
      with regard to effectivity and durability of results. The rate of secondary
      surgical procedures in HolEP, ThuVEP, bipolar enucleation and tangerine technique
      (TmLRP-TT) was 0-1.2 % for reTURP, 1.9-3.75 % for urethrotomy, and 0.9-4 % for
      bladder neck resection. No significant difference in the individual studies was
      found when compared to OP. For bipolar enucleation vs. TURP long-term results for
      uroflow, residual urine, and IPSS were significantly better at 60 months for
      bipolar enucleation. One RCT TmLRP-TT vs. TURP at the 48-month follow-up found no
      significant difference. CONCLUSION: Various transurethral EEP can be considered
      as equally safe and effective anatomical enucleation techniques. All displayed
      EEPs match the durability of OP. The choice of energy source for EEP seems to be
      secondary and a function of resources and personal preference of the skilled
      surgeon.

PMID- 27714418
TI  - Misty mesentery: a CT sign of mesenteric infiltration.

PMID- 27714419
TI  - The stepladder sign.

PMID- 27714415
TI  - Intravertebral cleft in pathological vertebral collapse resulting from cancer
      metastasis: report of three cases.
AB  - Intravertebral cleft (IVC) is a common finding in osteoporotic compression
      fracture. However, since the vertebral collapse attributable to cancer metastasis
      is rarely associated with IVC, the phenomenon is generally considered as a sign
      of a benign lesion. In this study, we retrospectively reviewed the radiographs,
      computed tomography scans, and magnetic resonance images of 111 patients with
      spinal metastasis. Three cases (2.7 %) had IVC in the collapsed thoracic
      vertebral bodies (T7, T8, and T11) attributable to cancer metastasis. IVC alone
      is not necessarily an indicator of a benign vertebral collapse.

PMID- 27714417
TI  - QTL mapping for downy mildew resistance in cucumber via bulked segregant analysis
      using next-generation sequencing and conventional methods.
AB  - KEY MESSAGE: QTL mapping using NGS-assisted BSA was successfully applied to an F
      2 population for downy mildew resistance in cucumber. QTLs detected by NGS
      assisted BSA were confirmed by conventional QTL analysis. Downy mildew (DM),
      caused by Pseudoperonospora cubensis, is one of the most destructive foliar
      diseases in cucumber. QTL mapping is a fundamental approach for understanding the
      genetic inheritance of DM resistance in cucumber. Recently, many studies have
      reported that a combination of bulked segregant analysis (BSA) and next
      generation sequencing (NGS) can be a rapid and cost-effective way of mapping
      QTLs. In this study, we applied NGS-assisted BSA to QTL mapping of DM resistance
      in cucumber and confirmed the results by conventional QTL analysis. By sequencing
      two DNA pools each consisting of ten individuals showing high resistance and
      susceptibility to DM from a F2 population, we identified single nucleotide
      polymorphisms (SNPs) between the two pools. We employed a statistical method for
      QTL mapping based on these SNPs. Five QTLs, dm2.2, dm4.1, dm5.1, dm5.2, and
      dm6.1, were detected and dm2.2 showed the largest effect on DM resistance.
      Conventional QTL analysis using the F2 confirmed dm2.2 (R 2 = 10.8-24 %) and
      dm5.2 (R 2 = 14-27.2 %) as major QTLs and dm4.1 (R 2 = 8 %) as two minor QTLs,
      but could not detect dm5.1 and dm6.1. A new QTL on chromosome 2, dm2.1 (R 2 =
      28.2 %) was detected by the conventional QTL method using an F3 population. This
      study demonstrated the effectiveness of NGS-assisted BSA for mapping QTLs
      conferring DM resistance in cucumber and revealed the unique genetic inheritance
      of DM resistance in this population through two distinct major QTLs on chromosome
      2 that mainly harbor DM resistance.

PMID- 27714424
TI  - [Epithelial skin tumors].

PMID- 27714416
TI  - Serum total bilirubin levels and disease severity in patients with stable
      coronary artery disease.
AB  - AIM: Serum total bilirubin (STB), a protective cardiovascular factor, was
      retrospectively investigated to determine the relationship between STB levels and
      the severity of disease in Chinese patients with stable coronary artery disease
      (CAD). PATIENTS AND METHODS: A total of 347 eligible patients presenting to our
      department from December 2007 to December 2012 were divided into tertiles
      according to their Syntax scores (low, moderate, and high). To clarify the
      association between STB levels and major adverse cardiovascular events (MACE),
      all patients were divided into two groups according to the median baseline STB
      (greater than or less than 13.2 MUmol/l), which was measured after at least 12-h
      fast. All participants were followed for a mean of 37.1 months for MACE,
      including all-cause death, recurrent nonfatal myocardial infarction, and
      recurrent percutaneous coronary intervention. RESULTS: The STB levels were
      significantly lower in the high Syntax score group than those of the other groups
      and were negatively correlated with the Syntax score and number of diseased
      vessels. Follow-up data showed a higher incidence of MACE in the low STB group
      compared with the high STB group. Elevated STB levels predict the long-term
      prognosis of patients with stable angina pectoris. Finally, Kaplan-Meier analysis
      showed a significantly higher event-free survival rate in the patients with high
      STB levels than those in the low STB group. CONCLUSIONS: STB levels were
      independently associated with the severity of disease in patients with stable
      CAD. Elevated STB is associated with cardiovascular events and may be useful as a
      biomarker of the severity and prognosis of stable CAD.

PMID- 27714421
TI  - Predictive ability of maximal tumor diameter on MRI for high-risk endometrial
      cancer.
AB  - AIM: To investigate the predictive ability of tumor size for deep myometrial
      invasion (>=50%) and metastatic lymphadenopathy, on maximal tumor diameter (MRI)
      of endometrial cancer. MATERIALS AND METHODS: Our study population consisted of
      105 patients (mean age: 59.8 years) with histologically confirmed endometrial
      cancer. All patients underwent preoperative pelvic MRI. Tumor maximal diameter
      (size) was calculated on multiple sequences, and the largest value was recorded.
      Logistic regression analysis was performed to investigate the association of
      maximal tumor diameter (MRI) with the depth of myometrial invasion and the
      presence of pelvic nodal metastases (histology); optimal tumor size cut-off for
      the prediction of deep myometrial involvement and nodal metastases was calculated
      using ROC analysis. Surgicopathological specimen examination was the standard of
      reference. RESULTS: Tumor size on MRI, independently predicted deep myometrial
      invasion. Optimal maximal tumor diameter cut-off for the prediction of deep
      myometrial invasion was 2 cm (SE 90%, SP 50.9%). When tumor size was used as a
      categorical variable in the multiple logistic regression model, tumor size >2 cm
      had 10.04 times greater odds of deep myometrial invasion (95% CI 3.34-30.17, p <
      0.001). Optimal tumor size cut-off for prediction of nodal metastases was 4 cm
      (SE 60%, SP 76.9%). Multiple logistic regression analysis with nodal metastases
      as a dependent variable showed that tumor size >4 cm had 4.79 times greater odds
      for malignant dissemination to the lymph nodes (95% CI 1.00-23.09, p = 0.047).
      CONCLUSION: Maximal tumor diameter on preoperative MRI may be yet another
      prognosticator for deep myometrial invasion and metastatic lymphadenopathy in
      patients with endometrial carcinoma.

PMID- 27714420
TI  - 3D T2-weighted and Gd-EOB-DTPA-enhanced 3D T1-weighted MR cholangiography for
      evaluation of biliary anatomy in living liver donors.
AB  - PURPOSE: To investigate whether the addition of gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced 3D T1-weighted MR
      cholangiography (T1w-MRC) to 3D T2-weighted MRC (T2w-MRC) improves the confidence
      and diagnostic accuracy of biliary anatomy in living liver donors. METHODS: Two
      abdominal radiologists retrospectively and independently reviewed pre-operative
      MR studies in 58 consecutive living liver donors. The second-order bile duct
      visualization on T1w- and T2w-MRC images was rated on a 4-point scale. The
      readers also independently recorded the biliary anatomy and their diagnostic
      confidence using (1) combined T1w- and T2w-MRC, and (2) T2w-MRC. In the 23 right
      lobe donors, the biliary anatomy at imaging and the imaging-predicted number of
      duct orifices at surgery were compared to intra-operative findings. RESULTS: T1w
      MRC had a higher proportion of excellent visualization than T2w-MRC, 66% vs. 45%
      for reader 1 and 60% vs. 31% for reader 2. The median confidence score for
      biliary anatomy diagnosis was significantly higher with combined T1w- and T2w-MRC
      than T2w-MRC alone for both readers (Reader 1: 3 vs. 2, p < 0.001; Reader 2: 3
      vs. 1, p < 0.001). Compared to intra-operative findings, the accuracy of imaging
      predicted number of duct orifices using combined T1w-and T2w-MRC was
      significantly higher than that using T2w-MRC alone (p = 0.034 for reader 1, p =
      0.0082 for reader 2). CONCLUSION: The addition of Gd-EOB-DTPA-enhanced 3D T1w-MRC
      to 3D T2w-MRC improves second-order bile duct visualization and increases the
      confidence in biliary anatomy diagnosis and the accuracy in the imaging-predicted
      number of duct orifices acquired during right lobe harvesting.

PMID- 27714422
TI  - Erratum to: Performance of cardiac cadmium-zinc-telluride gamma camera imaging in
      coronary artery disease: a review from the cardiovascular committee of the
      European Association of Nuclear Medicine (EANM).

PMID- 27714425
TI  - Acting with the future in mind is impaired in long-term opiate users.
AB  - RATIONALE: Episodic foresight is a fundamental human capacity. It refers to the
      ability to simulate future situations and organise current actions accordingly.
      While there is some evidence that opiate users have a reduced capacity to imagine
      themselves in future situations, no study to date has assessed whether opiate
      users show deficits in the ability to take steps in the present in anticipation
      of future needs. OBJECTIVE: In this study, we assessed whether this functional
      aspect of episodic foresight is impaired in chronic opiate users and the extent
      to which any deficits are associated with executive dysfunction. METHODS AND
      RESULTS: Participants were 33 long-term opiate users enrolled in an opiate
      substitution program and 34 controls. Relative to controls, the opiate users
      displayed significant impairment (medium effect size eta 2p = 0.08) in the two
      behavioural measures of episodic foresight used (items acquired and items used in
      the VW Foresight task). Furthermore, executive functioning was associated with
      foresight ability, although this was restricted to items acquired, and the
      associations were generally stronger for the control group. CONCLUSIONS: These
      data provide important evidence suggesting that the functional aspect of episodic
      foresight is disrupted in long-term opiate users. While these deficits appear to
      have some links to impaired executive control, additional work is needed to gain
      a more complete understanding of the underlying cognitive and neural mechanisms
      involved. This, in turn, will have important implications for tailoring
      interventions with opiate users to maximise the likelihood of successful
      independent functioning.

PMID- 27714423
TI  - Scientific principles for the identification of endocrine-disrupting chemicals: a
      consensus statement.
AB  - Endocrine disruption is a specific form of toxicity, where natural and/or
      anthropogenic chemicals, known as "endocrine disruptors" (EDs), trigger adverse
      health effects by disrupting the endogenous hormone system. There is need to
      harmonize guidance on the regulation of EDs, but this has been hampered by what
      appeared as a lack of consensus among scientists. This publication provides
      summary information about a consensus reached by a group of world-leading
      scientists that can serve as the basis for the development of ED criteria in
      relevant EU legislation. Twenty-three international scientists from different
      disciplines discussed principles and open questions on ED identification as
      outlined in a draft consensus paper at an expert meeting hosted by the German
      Federal Institute for Risk Assessment (BfR) in Berlin, Germany on 11-12 April
      2016. Participants reached a consensus regarding scientific principles for the
      identification of EDs. The paper discusses the consensus reached on background,
      definition of an ED and related concepts, sources of uncertainty, scientific
      principles important for ED identification, and research needs. It highlights the
      difficulty in retrospectively reconstructing ED exposure, insufficient range of
      validated test systems for EDs, and some issues impacting on the evaluation of
      the risk from EDs, such as non-monotonic dose-response and thresholds, modes of
      action, and exposure assessment. This report provides the consensus statement on
      EDs agreed among all participating scientists. The meeting facilitated a
      productive debate and reduced a number of differences in views. It is expected
      that the consensus reached will serve as an important basis for the development
      of regulatory ED criteria.

PMID- 27714430
TI  - Factors associated with the accuracy of self-reported osteoporosis in the
      community.
AB  - We examined the agreement between self-reported osteoporosis and bone mineral
      density (BMD) results through dual-energy x-ray absorptiometry (DXA) using data
      from a national representative sample taken from the US communities. Six-year
      data from the continuous National Health and Nutrition Examination Survey 2005
      2006, 2007-2008, and 2009-2010 were merged. Participants included adults 50 years
      of age or older whose data appeared in both questionnaire and medical examination
      data files. Self-reported osteoporosis was defined by an affirmative response to
      a question in the osteoporosis questionnaire then compared with BMD-defined
      osteoporosis, defined by BMD values taken from the examination data. Agreement
      between self-reported osteoporosis and DXA results were low. Kappa was only 0.24
      (95 % confidence interval = 0.21-0.27), and sensitivity and positive predictive
      value were 28.0 and 40.8 %, respectively. When stratified by gender or age group,
      agreement remained poor. Self-report of osteoporosis would not be suitable for
      accurate prevalence estimates for osteoporosis regardless of gender or age group.

PMID- 27714428
TI  - Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to
      heroin seeking in rodents.
AB  - RATIONALE: Relapse to opioids is often driven by the avoidance of the aversive
      states of opioid withdrawal. We recently demonstrated that activation of
      peroxisome proliferator-activated receptor gamma (PPARgamma) by pioglitazone
      reduces the motivation for heroin and attenuates its rewarding properties.
      However, the role of PPARgamma in withdrawal and other forms of relapse to heroin
      is unknown. OBJECTIVES: To further address this issue, we investigated the role
      of PPARgamma on the development and expression of morphine withdrawal in mice and
      the effect of pioglitazone on several forms of heroin relapse in rats. METHODS:
      We induced physical dependence to morphine in mice by injecting morphine twice
      daily for 6 days. Withdrawal syndrome was precipitated on day 6 with an injection
      of naloxone. In addition, different groups of rats were trained to self
      administer heroin and, after the extinction, the relapse was elicited by cues,
      priming, or stress. The effect of different doses of pioglitazone was tested on
      these different paradigms. RESULTS: Data show that chronic and acute
      administration of pioglitazone attenuates morphine withdrawal symptoms, and these
      effects are mediated by activation of PPARgamma receptors. Activation of
      PPARgamma by pioglitazone also abolishes yohimbine-induced reinstatement of
      heroin seeking and reduces heroin-induced reinstatement, while it does not affect
      cue-induced relapse. CONCLUSIONS: These findings provide new insights on the role
      of PPARgamma on opioid dependence and suggest that pioglitazone may be useful for
      the treatment of opioid withdrawal in opioid-addicted individuals.

PMID- 27714429
TI  - Alterations of consciousness and mystical-type experiences after acute LSD in
      humans.
AB  - RATIONALE: Lysergic acid diethylamide (LSD) is used recreationally and in
      clinical research. Acute mystical-type experiences that are acutely induced by
      hallucinogens are thought to contribute to their potential therapeutic effects.
      However, no data have been reported on LSD-induced mystical experiences and their
      relationship to alterations of consciousness. Additionally, LSD dose- and
      concentration-response functions with regard to alterations of consciousness are
      lacking. METHODS: We conducted two placebo-controlled, double-blind, cross-over
      studies using oral administration of 100 and 200 MUg LSD in 24 and 16 subjects,
      respectively. Acute effects of LSD were assessed using the 5 Dimensions of
      Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical
      Experience Questionnaire (MEQ) after 200 MUg. RESULTS: On the MEQ, 200 MUg LSD
      induced mystical experiences that were comparable to those in patients who
      underwent LSD-assisted psychotherapy but were fewer than those reported for
      psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced
      higher ratings of blissful state, insightfulness, and changed meaning of percepts
      after 200 MUg compared with 100 MUg. Plasma levels of LSD were not positively
      correlated with its effects, with the exception of ego dissolution at 100 MUg.
      CONCLUSIONS: Mystical-type experiences were infrequent after LSD, possibly
      because of the set and setting used in the present study. LSD may produce greater
      or different alterations of consciousness at 200 MUg (i.e., a dose that is
      currently used in psychotherapy in Switzerland) compared with 100 MUg (i.e., a
      dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD,
      whereas more robustly induced effects of LSD may not result in such associations.

PMID- 27714432
TI  - Abrupt transitions to tumor extinction: a phenotypic quasispecies model.
AB  - The dynamics of heterogeneous tumor cell populations competing with healthy cells
      is an important topic in cancer research with deep implications in biomedicine.
      Multitude of theoretical and computational models have addressed this issue,
      especially focusing on the nature of the transitions governing tumor clearance as
      some relevant model parameters are tuned. In this contribution, we analyze a
      mathematical model of unstable tumor progression using the quasispecies
      framework. Our aim is to define a minimal model incorporating the dynamics of
      competition between healthy cells and a heterogeneous population of cancer cell
      phenotypes involving changes in replication-related genes (i.e., proto-oncogenes
      and tumor suppressor genes), in genes responsible for genomic stability, and in
      house-keeping genes. Such mutations or loss of genes result into different
      phenotypes with increased proliferation rates and/or increased genomic
      instabilities. Despite bifurcations in the classical deterministic quasispecies
      model are typically given by smooth, continuous shifts (i.e., transcritical
      bifurcations), we here identify a novel type of bifurcation causing an abrupt
      transition to tumor extinction. Such a bifurcation, named as trans-heteroclinic,
      is characterized by the exchange of stability between two distant fixed points
      (that do not collide) involving tumor persistence and tumor clearance. The
      increase of mutation and/or the decrease of the replication rate of tumor cells
      involves this catastrophic shift of tumor cell populations. The transient times
      near bifurcation thresholds are also characterized, showing a power law
      dependence of exponent [Formula: see text] of the transients as mutation is
      changed near the bifurcation value. These results are discussed in the context of
      targeted cancer therapy as a possible therapeutic strategy to force a
      catastrophic shift by simultaneously delivering mutagenic and cytotoxic drugs
      inside tumor cells.

PMID- 27714427
TI  - Response to varying the nicotine content of cigarettes in vulnerable populations:
      an initial experimental examination of acute effects.
AB  - RATIONALE: The purpose of this study was to begin researching the effects of very
      low nicotine content cigarettes in smokers especially vulnerable to dependence to
      assess their potential as a less dependence-producing alternative to current
      commercial cigarettes. METHODS: Participants were 26 adult, daily cigarette
      smokers from one of three populations: economically disadvantaged women of
      reproductive age (n = 9), opioid-dependent individuals (n = 11), and individuals
      with affective disorders (n = 6). Participants completed fourteen 2-4-h
      experimental sessions in a within-subjects research design. Sessions were
      conducted following brief smoking abstinence. Four research cigarettes varying in
      nicotine content (0.4, 2.4, 5.2, and 15.8 mg/g) were studied under double-blind
      conditions, assessing smoking topography, subjective effects, and relative
      reinforcing effects of varying doses in concurrent choice tests. Results were
      collapsed across vulnerable populations and analyzed using repeated measures
      ANOVA. RESULTS: No significant differences between doses were discernible in
      smoking topography. All doses were equi-effective at reducing nicotine
      withdrawal. Ratings of satisfaction from smoking were lower at the 0.4 compared
      to 15.8 mg/g dose. Participants preferred the 15.8 mg/g dose over the 0.4 and 2.4
      but not the 5.2 mg/g doses in concurrent choice testing; no differences between
      the two lowest doses were noted. CONCLUSIONS: All cigarettes effectively reduced
      nicotine withdrawal with no differences in smoking topography, suggesting minimal
      compensatory smoking. Dependence potential was lowest at the 0.4 mg/g dose. These
      initial results are promising regarding the feasibility of lowering nicotine
      content in cigarettes to very low levels in vulnerable populations without
      untoward effects.

PMID- 27714431
TI  - Augmentative biocontrol when natural enemies are subject to Allee effects.
AB  - Intraspecific interactions such as Allee effects are key properties that can
      guide population management. This contribution considers component Allee effects
      that are elementary mechanisms leading to declines of fitness at the population
      scale, i.e. demographic Allee effects. It especially focuses on the consequences
      of such properties in predator populations, and investigates their repercussions
      in a biological control context. A modelling framework able to account for
      reproductive and/or foraging component Allee effects is proposed. From this, four
      models of augmentative biological control, corresponding to the periodic
      introduction of natural enemies, have been investigated. This is done using semi
      discrete models: ordinary differential equations are used to depict predator-prey
      dynamics and a discrete equation describes the abrupt augmentation of predators
      at periodic intervals. In that context, stability of a prey-free solution
      corresponding to pest eradication has been analyzed. It has been found that rare
      but large introductions should be preferred over frequent and small ones, when
      Allee effects influence predator populations. In particular, the occurrence of
      foraging, rather than reproducing, Allee effects significantly hinders pest
      eradication. Cases where the pest-free solution is locally, but not globally,
      stable were also observed and were shown to be favored by the occurrence of
      reproductive Allee effects among predators.

PMID- 27714426
TI  - Chronic administration of the dopamine D2/3 agonist ropinirole invigorates
      performance of a rodent slot machine task, potentially indicative of less
      distractible or compulsive-like gambling behaviour.
AB  - RATIONALE: Whilst dopamine agonist therapies can successfully manage the symptoms
      of diseases such as Parkinson's disease (PD), fibromyalgia and restless leg
      syndrome, they can also cause impulse control and addiction disorders such as
      gambling disorder (GD). These compulsive behaviours seriously undermine the
      utility of such treatments. OBJECTIVES: The objective of the study was to model
      this phenomenon using a rodent slot machine task (rSMT) in order to investigate
      the neurobiological basis underlying such behavioural changes. METHODS: Male Long
      Evans rats were trained to perform the rSMT. The D2-like agonist ropinirole, or
      saline, was then delivered continuously for 28 days via osmotic mini-pump. The
      effects of ropinirole on baseline rSMT performance, as well as extinction and
      reinstatement sessions, were determined during this time. Brain samples from key
      frontostriatal regions implicated in GD and PD were then harvested immediately or
      after a 4-week washout period during which behaviour returned to pre-drug
      baseline. RESULTS: Ropinirole invigorated task performance, in that drug
      treatment resulted in a robust and sustained increase in the number of trials
      completed. Ex vivo analyses revealed that chronic ropinirole treatment led to a
      pattern of changes indicative of upregulation within the beta-arrestin-AKT
      GSK3beta intracellular cascade, recently theorised to dominate D2-mediated
      signalling under hyperdopaminergic conditions, in the dorsal striatum, rather
      than the canonical PKA-dependent signalling pathway associated with D2 receptor
      activation. CONCLUSIONS: Such findings provide novel insight into the role of
      dopamine signalling in mediating compulsive-like gambling behaviour and may
      inform more directed pharmacotherapies for the treatment of both idiopathic and
      iatrogenic GD.

PMID- 27714435
TI  - Transobturator versus single incision slings: 1-year results of a randomized
      controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: To compare 1-year surgical outcomes following
      transobturator (TO) sling placement and single incision (SI) sling placement for
      the treatment of stress urinary incontinence (SUI). METHODS: We performed a
      randomized trial at a single institution. Patients with urodynamically proven SUI
      were offered participation and randomized to placement of a TO sling (MonarcTM)
      or a SI sling (MiniArcTM) between 2008 and 2011. The primary outcome measure was
      urinary leakage during standardized cough stress test (CST). Forty subjects in
      each group were required to achieve 80 % power to detect an effect size of 0.25.
      RESULTS: A total of 98 patients were randomized with 49 patients in the TO group
      and 49 patients in the SI group. Preoperative demographics were similar between
      the groups (Table 1). The TO group had a significantly longer sling operative
      time (10.7 +/- 4.8 min vs. 7.8 +/- 4.9 min, p < 0.001) and greater estimated
      blood loss (31.6 +/- 26.6 mL vs. 22.9 +/- 22.1 mL, p = 0.02). At the 1-year
      follow-up, there was no difference in the primary outcome with 9 TO patients (21
      %) and 12 SI patients (29 %) having a positive CST (p = 0.5). A composite
      measurement of 'failure', defined as patient-reported SUI and a positive CST,
      showed no difference between the TO group (17 %) and the SI group (27 %; p =
      0.3). CONCLUSIONS: The SI sling provides comparable objective efficacy to the TO
      sling at 1 year.

PMID- 27714433
TI  - Tumor-directed immunotherapy can generate tumor-specific T cell responses through
      localized co-stimulation.
AB  - The most important goals for the field of immuno-oncology are to improve the
      response rate and increase the number of tumor indications that respond to
      immunotherapy, without increasing adverse side effects. One approach to achieve
      these goals is to use tumor-directed immunotherapy, i.e., to focus the immune
      activation to the most relevant part of the immune system. This may improve anti
      tumor efficacy as well as reduce immune-related adverse events. Tumor-directed
      immune activation can be achieved by local injections of immune modulators in the
      tumor area or by directing the immune modulator to the tumor using bispecific
      antibodies. In this review, we focus on therapies targeting checkpoint inhibitors
      and co-stimulatory receptors that can generate tumor-specific T cell responses
      through localized immune activation.

PMID- 27714437
TI  - Dynamic knee behaviour: does the knee deformity change as it is flexed-an
      assessment and classification with computer navigation.
AB  - PURPOSE: The aim of this study was to assess the kinematics of arthritic knees
      prior to TKA. The hypothesis was that the arthritic knee follows distinct
      patterns with regard to deformity in coronal plane as it flexes from extended
      position. METHOD: Data from 585 consecutive arthritic knees that had undergone
      TKA using two non-image-based navigation systems were included in the study.
      Coronal plane alignment given by the femoro-tibial mechanical angle (FTMA) was
      recorded in extension, 30 degrees , 60 degrees , 90 degrees  and maximum flexion
      prior to making any bony cuts or ligamentous releases. RESULTS: Complete data
      were available for 512 (87.5 %) of arthritic knees. It was found that pre-implant
      arthritic knees behaved in different distinct patterns from full extension to 90
      degrees  flexion. These patterns in FTMA from extension through to 90 degrees  of
      flexion were classified into 4 major types (1, 2, 3, and 4) and 8 subgroups (1A,
      1B, 2A, 2B, 3, 4A, 4B, 4C) for varus and valgus knees. Beyond 90 degrees  of
      flexion, there were no distinct or consistent patterns. There were differences
      between varus and valgus knee deformities not only in overall numbers (73.8 %
      varus vs. 21.1 % valgus) but also in kinematic behaviour. Only 14.1 % of total
      knees had a consistent deformity (Type 1A) which remained the same throughout the
      range of flexion. 14.1 % knees actually become opposite deformity as the knee
      flexes; thus, varus becomes valgus and valgus becomes varus as the knee flexes
      (Type 3 and 4C). CONCLUSION: This study has observed and categorised distinct
      patterns which arthritic knees follow in the coronal plane as it flexes. This
      dynamic change during flexion will have bearing on collateral releases that are
      traditionally done based on deformity in extension or 90 degrees  flexion mainly.
      This may be the underlying cause of flexion instability especially for Types 3
      and 4C knees if collateral soft tissue release is done based on deformity in
      extension. Full significance of this remains unknown and will need further
      investigation. LEVEL OF EVIDENCE: III.

PMID- 27714434
TI  - Contemporary experience with high-dose interleukin-2 therapy and impact on
      survival in patients with metastatic melanoma and metastatic renal cell
      carcinoma.
AB  - High-dose interleukin-2 (HD IL-2) was approved for treatment of metastatic renal
      cell carcinoma (mRCC) in 1992 and for metastatic melanoma (mM) in 1998, in an era
      predating targeted therapies and immune checkpoint inhibitors. The PROCLAIMSM
      registry was established to collect and analyze data for patients treated with HD
      IL-2 in the current era. This analysis includes 170 patients with mM and 192
      patients with mRCC treated between 2005 and 2012 with survival data current as of
      July 27, 2015. For patients with mM, complete response (CR) was observed in 5 %,
      partial response (PR) in 10 %, stable disease (SD) in 22 %, and 63 % had
      progressive disease (PD). The median overall survival (mOS) for these patients
      was 19.6 months, with a median follow-up of 43.1 months. The mOS was not reached
      for patients achieving CR or PR, and was 33.4 months for patients with SD. For
      patients with mRCC, 6 % achieved CR, 9 % had PR, 22 % had SD, and 62 % had PD.
      The mOS was 41 months, with a median follow-up of 46.6 months. The mOS for
      patients who had CR and PR was not reached and was 49.6 months for patients with
      SD. There were no treatment-related deaths among 362 patients. The duration of
      mOS for patients with mM and mRCC is longer than historically reported. These
      data support a continued role for IL-2 in the treatment of eligible patients with
      mM or mRCC and warrant further evaluation of HD IL-2 in combination or sequence
      with other therapeutic agents.

PMID- 27714439
TI  - The Cumberland Ankle Instability Tool (CAIT) in the Dutch population with and
      without complaints of ankle instability.
AB  - PURPOSE: To develop a translated Dutch version of the Cumberland Ankle
      Instability Tool (CAIT) and test its psychometric properties in a Dutch
      population with foot and ankle complaints. METHODS: The CAIT was translated into
      the Dutch language using a forward-backward translation design. Of the 130
      subsequent patients visiting the outpatient clinic for foot and ankle complaints
      who were asked to fill out a questionnaire containing the CAIT, the Foot and
      Ankle Outcome Score (FAOS), and the numeric rating scale (NRS) pain, 98 completed
      the questionnaire. After a 1-week period, patients were asked to fill out a
      second questionnaire online containing the CAIT and NRS pain. This second
      questionnaire was completed by 70 patients. With these data, the construct
      validity, test-retest reliability, internal consistency, measurement error, and
      ceiling and floor effects were assessed. Additionally, a cut-off value to
      discriminate between stable and unstable ankles, in patients with ankle
      complaints, was calculated. RESULTS: Construct validity showed moderate
      correlations between the CAIT and FAOS subscales (Spearman's correlation
      coefficient (SCC) = 0.36-0.43), and the NRS pain (SCC = -0.55). The cut-off value
      was found at 11.5 points of the total CAIT score (range 0-30). Test-retest
      reliability showed to be excellent with an intraclass correlation coefficient of
      0.94. Internal consistency was high (Cronbach's alpha = 0.86). No ceiling or
      floor effects were detected. CONCLUSION: Based on the results, the Dutch version
      of the CAIT is a valid and reliable questionnaire to assess ankle instability in
      the Dutch population and is able to differentiate between a functionally unstable
      and stable ankle. The tool is the first suitable tool to objectify the severity
      of ankle instability specific complaints and assess change in the Dutch
      population. Level of evidence II.

PMID- 27714438
TI  - High mid-term revision rate after treatment of large, full-thickness cartilage
      lesions and OA in the patellofemoral joint using a large inlay resurfacing
      prosthesis: HemiCAP-Wave(r).
AB  - PURPOSE: The HemiCAP-Wave(r) implant for the patellofemoral resurfacing treatment
      of large cartilage lesions and osteoarthritis (OA) was introduced in 2009. The
      outcome of a prospective cohort study of 18 patients with large trochlea lesions
      or isolated OA treated with the HemiCAP-Wave(r) implant is presented with up to a
      6-year survival rate, and hypothesised short-to mid-term reduced pain and
      improved function. METHODS: Indication for treatment with the HemiCAP-Wave(r)
      implant was a symptomatic, large cartilage lesion in trochlea demonstrated by MRI
      or arthroscopy, which was ICRS grades 3-4 and larger than 4 cm2. Patients were
      followed for 2 years with American Knee Society Subjective outcome Scores (AKSS),
      pain scores and radiographic evaluations and for up to 6 years with complications
      and reoperations. RESULTS: At the 1- and 2-year follow-up mean AKSS clinical
      score, the mean AKSS function score and mean pain score improved significantly.
      Within 6 years, 28 % of the implants were revised to arthroplasty due to the
      progression of cartilage lesions, osteoarthritis or increased knee pain.
      CONCLUSION: The present study demonstrated an improved short- to mid-term
      clinical outcome and reduced pain but high mid-term revision rate after
      patellofemoral inlay resurfacing using the HemiCAP-Wave(r) implant.
      Patellofemoral resurfacing implantation treatment with a large inlay prosthesis
      can offer temporary treatment for large isolated patellofemoral cartilage lesions
      or OA in younger patients with almost healthy cartilage in the other compartments
      who are not yet eligible for arthroplasty treatment. LEVEL OF EVIDENCE: IV.

PMID- 27714436
TI  - Suprapubic versus transurethral bladder drainage following reconstructive pelvic
      surgery: a comparison of patient satisfaction and quality of life.
AB  - INTRODUCTION AND HYPOTHESIS: To assess the differences in patient-reported,
      catheter-specific satisfaction and quality of life with either suprapubic or
      transurethral postoperative bladder drainage following reconstructive pelvic
      surgery. METHODS: This was a prospective study of all eligible women who were
      scheduled to undergo reconstructive surgery requiring bladder drainage during the
      study period November 2013 to March 2015. Women who did not undergo the planned
      procedure(s) or did not require bladder drainage were excluded. The primary
      outcome was patient-reported quality of life using catheter-specific instruments
      including the Catheter-related Quality of Life (CIQOL) instrument, and a modified
      version of the Intermittent Self-Catheterization Questionnaire (ISC-Q), designed
      to evaluate aspects of catheter-related quality of life and satisfaction specific
      to the needs of the individual. RESULTS: A total of 178 women were analyzed, 108
      in the transurethral catheter group and 70 in the suprapubic group. Women with
      suprapubic bladder drainage had higher quality of life and satisfaction scores
      than women with transurethral bladder drainage as measured by the ISC-Q (68.31 +/
      16.87 vs. 54.04 +/- 16.95, mean difference 14.27, 95 % CI 9.15 - 19.39). There
      was no difference in quality of life by the CIQOL. After regression analysis,
      women with suprapubic bladder drainage were more satisfied with their catheter
      specific needs despite longer duration of catheter use, more concurrent
      continence surgery, and higher trait anxiety. CONCLUSIONS: Differences in
      catheter-specific quality of life and patient satisfaction scores favoring
      suprapubic bladder drainage support its continued use in appropriately selected
      women for treatment of temporary postoperative urinary retention after
      reconstructive pelvic surgery.

PMID- 27714442
TI  - Excess mortality following hip fracture: impact of self-perceived health,
      smoking, and body mass index. A NOREPOS study.
AB  - : Self-perceived health, smoking, and body mass index measured years before the
      hip fracture predicted excess post-hip fracture mortality, and even hip fracture
      patients with the most favorable levels of these risk factors had higher
      mortality than subjects who did not fracture. INTRODUCTION: This study aimed to
      investigate the impact of pre-fracture self-perceived health, smoking, and body
      mass index (BMI) on excess post-hip fracture mortality using matched peers
      without hip fracture as reference. METHODS: The study was based on the Cohort of
      Norway (CONOR) consisting of 10 regional health studies (1994-2003) and the
      NOREPOS hip fracture database (1994-2008). A matched cohort design was used to
      compare survival between hip fracture patients and subjects without fracture
      (matched on gender, age at participation in CONOR, and study site). Subjects aged
      >=60 years were included. Hazard ratios were estimated using stratified Cox
      regression. Age-standardized mortality was also calculated. RESULTS: Overall, hip
      fracture patients (N = 3177) had a 2.26-fold (95 % CI 2.13, 2.40) increased
      mortality compared to matched subjects (N = 20,282). The highest excess mortality
      was found in hip fracture patients reporting poor health (HR 4.08, 95 % CI 3.17,
      5.26) and daily smoking (HR 3.25, 95 % CI 2.89, 3.66) and in patients with BMI
      <18.5 (HR 3.07, 95 % CI 2.11, 4.47) prior to the fracture. However, excess
      mortality was also observed in hip fracture patients in all other categories of
      BMI, self-perceived health, and smoking. CONCLUSIONS: Information on self
      perceived health, smoking, and BMI collected years before hip fracture predicted
      excess post-hip fracture mortality, and even hip fracture patients with the most
      favorable levels of these risk factors had higher mortality than the matched
      subjects who did not fracture. This suggests that both pre-fracture health status
      and factors related to the hip fracture itself might affect post-hip fracture
      mortality.

PMID- 27714440
TI  - Celiac disease is associated with reduced bone mineral density and increased FRAX
      scores in the US National Health and Nutrition Examination Survey.
AB  - : We investigated the association between celiac disease (CD) and bone mass
      density (BMD) and risk of osteoporotic fractures in the general US population. In
      children and men >=18 years, CD was associated with reduced BMD, and in men >=40
      years, CD was associated with increased risk of osteoporotic fractures.
      INTRODUCTION: Celiac disease (CD) is an autoimmune condition, characterized by
      inflammation of the small intestine. CD has an increasing prevalence, and if
      unrecognized or untreated, CD can lead to complications from malabsorption and
      micronutrient deficiencies. We aimed to study whether CD is an independent
      predictor of reduced bone mineral density (BMD) and FRAX scores in the general US
      population. METHODS: We used data from the National Health and Nutrition
      Examination Survey, 2009-2010 and 2013-2014. CD was defined by positive tissue
      transglutaminase IgA antibody test. Multivariable models of BMD and FRAX scores
      were adjusted for BMI, serum 25-hydroxyvitamin D, vitamin D and calcium
      supplements, milk intake, serum calcium, and smoking status, when available.
      RESULTS: In children, aged 8-17 years, CD was associated with decreased Z-scores,
      by 0.85 for hip and 0.46 for spine (both P < 0.001). In men aged >= 18 years, CD
      was associated with 0.06 g/cm2 decrease in BMD in hip and with 0.11 g/cm2
      decrease in BMD in spine (P = 0.08 and P < 0.001, respectively). In women, there
      were no statistically significant differences in the multiple-adjusted model. In
      men aged >= 40 years, CD predicted FRAX scores, resulting in increased scores by
      2.25 % (P = 0.006) for hip fracture and by 2.43 % (P = 0.05) for major
      osteoporotic fracture. CD did not predict FRAX scores in women aged >=40 years.
      CONCLUSION: CD is independently associated with reduced BMD in children and
      adults aged >=18 years and is an independent risk factor of osteoporotic
      fractures in men aged >=40 years.

PMID- 27714446
TI  - Key elements of metabolomics in the study of biomarkers of diabetes.
AB  - Metabolomics is instrumental in the analysis of disease mechanisms and biomarkers
      of disease. The human metabolome is influenced by genetics and environmental
      interactions and reveals characteristic signatures of disease. Population studies
      with metabolomics require special study designs and care needs to be taken with
      pre-analytics. Gas chromatography coupled to mass spectrometry, liquid
      chromatography coupled to mass spectrometry or NMR are popular techniques used
      for metabolomic analyses in human cohorts. Metabolomics has been successfully
      used in the biomarker search for disease prediction and progression, for analyses
      of drug action and for the development of companion diagnostics. Several
      metabolites or metabolite classes identified by metabolomics have gained much
      attention in the field of diabetes research in the search for early disease
      detection, differentiation of progressor types and compliance with medication.
      This review summarises a presentation given at the 'New approaches beyond
      genetics' symposium at the 2015 annual meeting of the EASD. It is accompanied by
      another review from this symposium by Bernd Mayer (DOI: 10.1007/s00125-016-4032-2
      ) and an overview by the Session Chair, Leif Groop (DOI: 10.1007/s00125-016-4014
      4 ).

PMID- 27714448
TI  - Paul of Aegina (ca 625-690 AD), and his orthopaedic surgical reconstruction of
      the preternatural fingers.
AB  - Paul of Aegina lived in a era when the preservation of the ancient Greek
      tradition was for him almost a necessity. Eager to follow the dogma of
      "orhothetaopio(epsilon)deltaomega" (orthopodo: pace with no malformation), he
      introduced a series of surgical operations of reconstructive-cosmetic-plastic
      orthopaedic nature to confront any disfiguration of the human body. The aim of
      our study is to present the atmosphere of the era concerning the congenital
      malformations, describe briefly Paul's contribution on classic orthopaedics and
      present his views on the preternatural fingers. Our methodology mainly included
      the indexing of Paul's treatise, as published by the Sydenham Society during the
      nineteenth century, while references from the ancient Greek scholars were added
      to compose a better understanding of Paul's views. Inside his seven book treatise
      "Medical Compendium", he dedicated a separate chapter "On preternatural fingers,
      and on persons having six fingers", to introduce a detailed description of the
      extremities' additional digits and propose surgical treatment for their
      correction. He classified polydactylism according both to the presence of bones
      and to the anatomical origin of each additional finger. Paul marked the beginning
      of a new era for orthopaedics.

PMID- 27714441
TI  - Facilitators and barriers to exercise adherence in patients with osteopenia and
      osteoporosis: a systematic review.
AB  - : The aim of this study was to categorize the facilitators and barriers of
      exercise and identify methods to promote exercise adherence in the osteoporosis
      population. Despite the fair methodological quality of included randomized
      controlled trials (RCTs), less than 75 % identified facilitators and barriers to
      exercise. Methods to promote and measure exercise adherence were poorly reported.
      INTRODUCTION: Several studies have shown exercise to be successful in maintaining
      or increasing BMD in individuals with low bone mass. Yet, adherence to exercise
      is poor, with 50 % of those registered in an exercise program dropping out within
      the first 6 months, lack of time being the number one barrier in many
      populations. However, in the osteoporosis population, the main facilitator and
      barrier to exercise is still unclear. The aim of this study is to examine the
      extent to which RCTs reported the facilitators and the barriers to exercise and
      identified methods to promote adherence to an exercise program. METHODS: PubMed,
      CINHAL, EMBASE, and the Cochrane Review were queried using a predefined search
      criterion, and the resulting citations were imported into DistillerSR. Screening
      was carried out by two independent reviewers, and articles were included in the
      analysis by consensus. The methodological quality of included studies was
      assessed using the PEDro scale. RESULTS: Fifty-four RCTs examining exercise
      interventions in patients with osteopenia or osteoporosis were included. A
      spectrum of facilitators and barriers to exercise for osteoporotic patients were
      identified; however, no one facilitator was more frequently reported than the
      other. The most commonly reported barriers were lack of time and transportation.
      In most RCTs, methods to promote and measure exercise adherence were
      unsatisfactory. Of the 54 papers, 72 % reported an adherence rate to an exercise
      program; the lowest reported rate was 51.7 %, and the highest 100 %. CONCLUSIONS:
      Most RCTs found were of fair quality; however, less than three quarters
      identified facilitators and barriers to exercise. Reporting of methods to promote
      and measure exercise adherence were low. Future work should be directed toward
      identifying major facilitators and barriers to exercise adherence within RCTs.
      Only then can methods be identified to leverage facilitators and overcome
      barriers, thus strengthening the evidence for efficacy of optimal interventional
      exercise programs. This review has been registered in PROSPERO under registration
      number CRD42016039941.

PMID- 27714447
TI  - Alpha-defensin-novel synovial fluid biomarker for the diagnosis of periprosthetic
      joint infection.
AB  - PURPOSE: Periprosthetic joint infection (PJI) continues to be a significant
      complication after total joint arthroplasty. Diagnosis of PJI can be challenging
      and elusive in the absence of a gold standard. This purpose of this article is to
      review the current evidence on the utility of serum and synovial fluid biomarkers
      to help aid in the diagnosis of PJI with focusing on synovial fluid alpha
      defensin. METHODS: Articles and data for this review were identified by searches
      of PubMed and Ovid MEDLINE up to June 1, 2016. In addition, we manually reviewed
      the bibliographies of the retrieved articles for additional citations for
      references from relevant articles on the diagnosis of PJI. RESULTS: Serum
      biomarkers can be elevated in various inflammatory conditions. Synovial fluid
      biomarkers are more accurate for the diagnosis of PJI compared to serum
      biomarkers. Based on current available data, alpha-defensin is the most promising
      synovial fluid biomarker for the diagnosis of PJI and is commercially available.
      CONCLUSIONS: Synovial fluid alpha-defensin could enhance our ability to identify
      PJI and incorporate into the diagnostic algorithm in the future. Large-scale
      studies are needed to provide more data for its significance for the diagnosis of
      PJI.

PMID- 27714451
TI  - Kinematic femoral alignment with gap balancing and patient-specific
      instrumentation in total knee arthroplasty: a randomized clinical trial.
AB  - While patient-specific instrumentation (PSI) in total knee arthroplasty (TKA)
      allows for transfer of the preoperative plan onto bony landmarks, the soft tissue
      balancing is not affected. The goals of this randomized clinical trial were to
      compare PSI and the measured resection technique (conventional) with PSI and the
      gap balancing technique. Fifty patients were randomized to TKA with conventional
      PSI (PSI-S) (n = 25) or to PSI with additional gap balancing (PSI-GB) (n = 25).
      All patients were clinically examined at 3 and 12 months postoperatively. Data on
      the range of motion, the Knee Society Score, the Western Ontario and McMasters
      Universities Osteoarthritis Index, the High-Flexion Knee Score (HFKS), and the
      Forgotten Joint Score (FJS) were compiled at follow-up. Statistically significant
      improvements were found for all clinical parameters in the PSI-GB group compared
      to the PSI-S group at 3 months postoperatively and for FS, FJS, and HFKS at 12
      months. However, the relevance of these differences, as well as their effect on
      long-term outcomes, needs to be evaluated further. In conclusion, patient
      specific instrumentation combined with gap balancing yielded good early clinical
      outcomes.

PMID- 27714450
TI  - Metabolic acidosis with hemodilution due to massive absorption of normal saline
      as bladder irrigation fluid following holmium laser enucleation of prostate.
AB  - Holmium laser enucleation of prostate (HoLEP) is being performed with increasing
      frequency as a minimally invasive alternative to transurethral resection of the
      prostate (TURP) for the surgical management of benign prostatic hyperplasia
      (BPH). HoLEP offers the advantage of use of normal saline for irrigation, instead
      of glycine which is utilized in TURP, decreasing the likelihood of fluid
      absorption and effects on serum electrolytes. We describe a patient who underwent
      HoLEP for BPH and subsequently developed non-ion gap metabolic acidosis and
      hemodilution associated with volume overload.

PMID- 27714443
TI  - Incident atrial fibrillation and the risk of fracture in the cardiovascular
      health study.
AB  - : In this prospective cohort of 4462 older adults, incident atrial fibrillation
      (AF) was not statistically significantly associated with subsequent risk of
      incident fracture. INTRODUCTION: AF is associated with stroke, heart failure,
      dementia, and death, but its association with fracture is unknown. Therefore, we
      examined the association of incident AF with the risk of subsequent fracture in
      the Cardiovascular Health Study (CHS) cohort. METHODS: Of the CHS participants
      aged >=65 years, 4462 were followed between 1991 and 2009, mean follow-up 8.8
      years. Incident AF was identified by annual study electrocardiogram (ECG),
      hospital discharge diagnosis codes, or Medicare claims. Fractures of the hip,
      distal forearm, humerus, or pelvis were identified using hospital discharge
      diagnosis codes or Medicare claims. We used Cox proportional hazard models to
      estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the
      association between incident AF (time-varying) and the risk of subsequent
      fracture. We also evaluated whether AF was associated with risk of sustaining a
      fall. RESULTS: Crude incident fracture rate was 22.9 per 1000 person-years in
      participants with AF and 17.7 per 1000 person-years in participants without AF.
      Individuals with incident AF were not at significantly higher risk of hip
      fracture (adjusted HR = 1.09, 95 % CI 0.83-1.42) or fracture at any selected site
      (adjusted HR = 0.97, 95 % CI 0.77-1.22) or risk of sustaining a fall (adjusted HR
      = 1.00, 95 % CI = 0.87-1.16) compared with those without AF. CONCLUSION: In this
      cohort of older, community-dwelling adults, incident AF was not shown to be
      associated with falls or hip or other fractures.

PMID- 27714449
TI  - Wearable cardioverter defibrillator.

PMID- 27714444
TI  - Green methods of lignocellulose pretreatment for biorefinery development.
AB  - Lignocellulosic biomass is the most abundant, low-cost, bio-renewable resource
      that holds enormous importance as alternative source for production of biofuels
      and other biochemicals that can be utilized as building blocks for production of
      new materials. Enzymatic hydrolysis is an essential step involved in the
      bioconversion of lignocellulose to produce fermentable monosaccharides. However,
      to allow the enzymatic hydrolysis, a pretreatment step is needed in order to
      remove the lignin barrier and break down the crystalline structure of cellulose.
      The present manuscript is dedicated to reviewing the most commonly applied
      "green" pretreatment processes used in bioconversion of lignocellulosic biomasses
      within the "biorefinery" concept. In this frame, the effects of different
      pretreatment methods on lignocellulosic biomass are described along with an in
      depth discussion on the benefits and drawbacks of each method, including
      generation of potentially inhibitory compounds for enzymatic hydrolysis, effect
      on cellulose digestibility, and generation of compounds toxic for the
      environment, and energy and economic demand.

PMID- 27714452
TI  - Malaria relapses were already known before 1900-a discussion.
AB  - For a long time, only two phases of the life cycle of the agents of malaria
      parasites were known: the cycle inside the mosquito body and the cycle in the red
      blood cells of humans as intermediate hosts. A possible tissue development cycle
      inside humans, however, had already been proposed before 1900. In general, Pieter
      Klaesz Pel is considered the first scientist who has described such a tissue
      cycle. However, a closer look at Pel's work shows that he still followed an old
      (conservative) way of thinking, since he still referred to "malaria poison and
      malaria miasma." Thus, the first idea of a possible tissue cycle must be searched
      in the work of earlier scientists. Referring to their observations on malaria,
      Vassilij Danilevsky, Arman Ruffer, Camillo Golgi and Battista Grassi suspected
      developing parasites in internal organs, before they can be found in the
      bloodstream.

PMID- 27714453
TI  - Life cycle and biology of Tristriata anatis (Digenea: Notocotylidae):
      morphological and molecular approaches.
AB  - Notocotylids are common digeneans parasitising birds and mammals. They have a two
      host life cycle with cercariae encysting in the open. Particular life cycles
      remain unknown for majority of notocotylid species, including a common parasite
      of sea ducks Tristriata anatis. Here we resolve the life cycle of T. anatis by
      means of D2 LSU, ITS1 and CO1 DNA sequence analysis, showing that the first
      intermediate hosts for this species are periwinkles Littorina spp. Morphological
      descriptions of rediae and cercariae are provided for the first time, and we also
      supplement the existing morphological data on adults. Apart from differential
      diagnosis, we discuss some features of cercariae and rediae biology, geographical
      distribution and host range. Our molecular data confirm that genus Tristriata is
      monotypic and that T. anatis has circumpolar distribution. CO1 sequence analysis
      has shown that isolation exists between the Atlantic and Pacific populations of
      T. anatis, suggesting that there are geographical races. We suppose that their
      formation may be linked to the Last Ice Age events, when trans-Arctic bird
      migrations ceased and periwinkle ranges shrunk. These made transfer of parasites
      across the Arctic impossible, and it still has not resumed. We discuss the
      possible influence of host vagility and adults' lifespan on digeneans' potential
      for geographical colonisation.

PMID- 27714462
TI  - Preoperative elevated platelet count and thrombocytosis in gynecologic
      malignancies.
AB  - PURPOSE: Platelets have multiple functions and they also play an important role
      in malignancies. Elevated platelet count and thrombocytosis at the time of
      diagnosis in patients with many solid tumors correlates with prognosis and is
      associated with poor survival. The aim of the following report is to review the
      literature concerning elevated platelet count and thrombocytosis in gynecologic
      malignancies. METHOD: A PubMed search of all English literature peer-reviewed
      publications was performed containing the terms elevated platelet count or
      thrombocytosis and vulvar cancer, cervical cancer, endometrial cancer, and
      ovarian cancer. All studies published until December 31, 2015, were included in
      the following review. RESULTS: A pretreatment elevated platelet count and
      thrombocytosis have been shown to be associated with a poor prognosis in many
      studies of gynecologic malignancies with the exception of vulvar carcinoma.
      CONCLUSION: Since elevated platelet count and thrombocytosis may be prevented by
      blocking thrombopoietic cytokines, their assessment may, in the future, be of
      therapeutic significance.

PMID- 27714461
TI  - Lithium chloride enhances bone regeneration and implant osseointegration in
      osteoporotic conditions.
AB  - Osteoporotic patients have a high risk of dental and orthopedic implant failure.
      Lithium chloride (LiCl) has been reported to enhance bone formation. However, the
      role of LiCl in the success rate of dental and orthopedic implants in
      osteoporotic conditions is still unknown. We investigated whether LiCl enhances
      implant osseointegration, implant fixation, and bone formation in osteoporotic
      conditions. Sprague-Dawley female rats (n = 18) were ovariectomized (OVX) to
      induce osteoporosis, and another nine rats underwent sham surgery. Three months
      after surgery, titanium implants were implanted in the tibia of the OVX and sham
      group rats. After implantation, the OVX rats were gavaged with 150 mg/kg/2 days
      of LiCl (OVX + LiCl group) or saline (OVX group), and sham group rats were
      gavaged with saline for 3 months. Implant osseointegration and bone formation
      were analyzed using histology, biomechanical testing, and micro computed
      tomography (micro-CT). More bone loss was observed in the OVX group compared to
      the control, and LiCl treatment enhanced bone formation and implant fixation in
      osteoporotic rats. In the OVX group, bone-implant contact (BIC) was decreased by
      81.2 % compared to the sham group. Interestingly, the OVX + LiCl group showed 4.4
      fold higher BIC compared to the OVX group. Micro-CT data of tibia from the OVX +
      LiCl group showed higher bone volume, trabecular thickness, trabecular number,
      and osseointegration compared to the OVX group. Maximum push-out force and
      implant-bone interface shear strength were 2.9-fold stronger in the OVX + LiCl
      group compared to the OVX group. In conclusion, LiCl enhanced implant
      osseointegration, implant fixation, and bone formation in osteoporotic
      conditions, suggesting LiCl as a promising therapeutic agent to prevent implant
      failure and bone loss in osteoporotic conditions.

PMID- 27714454
TI  - Plant-specific 4/1 polypeptide interacts with an endoplasmic reticulum protein
      related to human BAP31.
AB  - MAIN CONCLUSION: The plant-specific 4/1 protein interacts, both in yeast two
      hybrid system and in vitro, and co-localizes in plant cells with plant BAP-like
      protein, the orthologue of human protein BAP31. In yeast two-hybrid system, we
      identified a number of Nicotiana benthamiana protein interactors of Nt-4/1, the
      protein known to affect systemic transport of potato spindle tuber viroid. For
      one of these interactors, an orthologue of human B-cell receptor-associated
      protein 31 (BAP31) termed plant BAP-like protein (PBL), the ability to interact
      with Nt-4/1 was studied in greater detail. Analyses of purified proteins
      expressed in bacterial cells carried out in vitro with the surface plasmon
      resonance (SPR) spectroscopy revealed that the N. tabacum PBL (NtPBL) was able to
      interact with Nt-4/1 with high-affinity, and that their complex can form at
      physiologically relevant concentrations of both proteins. Subcellular
      localization studies of 4/1-GFP and NtPBL-mRFP transiently co-expressed in plant
      cells revealed the co-localization of the two fusion proteins in endoplasmic
      reticulum-associated bodies, suggesting their interaction in vivo. The N-terminal
      region of the Nt-4/1 protein was found to be required for the specific
      subcellular targeting of the protein, presumably due to a predicted amphipathic
      helix mediating association of the Nt-4/1 protein with cell membranes.
      Additionally, this region was found to contain a trans-activator domain
      responsible for the Nt-4/1 ability to activate transcription of a reporter gene
      in yeast.

PMID- 27714459
TI  - Sodium hyaluronate: an effective adjunct in temporomandibular joint
      arthrocentesis.
AB  - BACKGROUND: Internal derangement of the temporomandibular joint (TMJ) is one of
      the most common forms of temporomandibular disorders. The minimally invasive
      treatments such as arthrocentesis as well as arthroscopic lysis and lavage are
      often used as a first-line surgical treatment or in conjunction with nonsurgical
      modalities with low morbidity and high efficacy. Sodium hyaluronate (SH) has been
      proposed as an alternative therapeutic agent with similar therapeutic effects.
      OBJECTIVE: A prospective study was carried out for evaluation of efficacy of TMJ
      arthrocentesis with and without injection of SH in management of internal
      derangements. MATERIAL AND METHODS: A total of 30 patients suffering from
      internal derangement of TMJ were selected for this study. Patients were randomly
      divided into the following two groups: group 1-arthrocentesis-only group and
      group 2-arthrocentesis + SH group. Each group constituted 15 patients. RESULTS:
      Six-month postoperative mean mouth opening (MMO) increase was 13.61 +/- 1.64 and
      15.53 +/- 3.01 mm in group 1 and group 2, respectively. At 6 months, there was
      marked improvement in masticatory efficiency with mean increase of 5.07 +/- 0.13
      in group 1 and 6.40 +/- 0.04 in group 2. Mean pain reduction was 5.27 +/- 0.67
      and 6.48 +/- 0.44 in group 1 and group 2, respectively. CONCLUSION: Although our
      series comprised a limited number of cases and a short follow-up period, initial
      results suggested that arthrocentesis with SH injection seemed to be superior to
      art.

PMID- 27714458
TI  - An interictal EEG can predict the outcome of vagus nerve stimulation therapy for
      children with intractable epilepsy.
AB  - PURPOSE: This study aimed to evaluate the long-term efficacy of vagus nerve
      stimulation (VNS) in children and adolescents with intractable epilepsy and
      identify predictive factors for responsiveness to VNS. METHODS: Medical records
      of pediatric patients who underwent VNS implantation at two Korean tertiary
      centers were reviewed. At 0.5, 1, 3, and 5 years post-VNS implantation, the
      frequency of the most disabling seizures in each patient was assessed. Responders
      were defined as showing an overall 50 % reduction from baseline seizure frequency
      during follow-up. The clinical characteristics of responders and non-responders
      were compared. RESULTS: Among 58 patients, approximately half (29/58) were
      responders. The mean age at implantation was 10.9 years (range, 2.7-20.9) and the
      mean follow-up duration after VNS implantation was 8.4 years (range, 1-15.5). At
      0.5, 1, 3, and 5 years after implantation, 43.1, 50.0, 56.9, and 58.1 % of
      patients exhibited >=50 % seizure frequency reduction disabling seizures. The
      patients with focal or multifocal epileptiform discharges were more likely to be
      responders than those with generalized epileptiform activities by video or
      conventional EEG at the time of VNS implantation (Pearson's and chi 2 test, p =
      0.001). No other clinical variables were found to be associated with seizure
      outcomes. Wound infections caused VNS removal in two cases. All other adverse
      events, including cough and hoarseness, were tolerable. CONCLUSION: VNS is a well
      tolerated and effective adjuvant therapy in pediatric patients with intractable
      epilepsy. Notably, patients with focal epileptiform discharges alone rather than
      those with generalized epileptiform discharges maybe better candidates for VNS.

PMID- 27714456
TI  - Characterizing cerebral and locomotor muscle oxygenation to incremental ramp
      exercise in healthy children: relationship with pulmonary gas exchange.
AB  - AIMS: To characterize the oxygenation responses at cerebral and locomotor muscle
      level to incremental exercise in children and to assess the interrelationship
      with the pulmonary gas exchange responses. METHODS: Eighteen children (9 boys, 9
      girls) (mean age 10.9 +/- 1.0 years) performed incremental cycle ramp exercise to
      exhaustion. The concentration of cerebral and muscle oxygenated (O2Hb) and
      deoxygenated (HHb) hemoglobin (by means of near-infrared spectroscopy) and
      pulmonary gas exchange was recorded. Cerebral and muscle O2Hb and HHb values were
      expressed as functions of oxygen uptake (VO2) and breakpoints were detected by
      means of double linear model analysis. The respiratory compensation point (RCP)
      was determined. The breakpoints in cerebral and muscle O2Hb and HHb were compared
      and correlated to RCP. RESULTS: The subjects reached peak power output of 105 +/-
      18 W and VO2peak of 43.5 +/- 7.0 ml min-1 kg-1. Cerebral O2Hb increased to an
      intensity of 89.4 +/- 5.5 %VO2peak, where a breakpoint occurred at which cerebral
      O2Hb started to decrease. Cerebral HHb increased slightly to 88.1 +/- 4.8
      %VO2peak, at which the increase was accelerated. Muscle HHb increased to 90.5 +/-
      4.8 %VO2peak where a leveling-off occurred. RCP occurred at 89.3 +/- 4.3
      %VO2peak. The breakpoints and RCP did not differ significantly (P = 0.13) and
      were strongly correlated (r > 0.70, P < 0.05). There were no differences between
      boys and girls (P = 0.43) and there was no significant correlation with VO2peak
      (P > 0.05). CONCLUSIONS: It was shown that cerebral and muscle oxygenation
      responses undergo significant changes as work rate increases and show breakpoints
      in the ongoing response at high intensity (85-95 %VO2peak). These breakpoints are
      strongly interrelated and associated with changes in pulmonary gas exchange.

PMID- 27714445
TI  - Human milk and mucosal lacto- and galacto-N-biose synthesis by
      transgalactosylation and their prebiotic potential in Lactobacillus species.
AB  - Lacto-N-biose (LNB) and galacto-N-biose (GNB) are major building blocks of free
      oligosaccharides and glycan moieties of glyco-complexes present in human milk and
      gastrointestinal mucosa. We have previously characterized the phospho-beta
      galactosidase GnbG from Lactobacillus casei BL23 that is involved in the
      metabolism of LNB and GNB. GnbG has been used here in transglycosylation
      reactions, and it showed the production of LNB and GNB with N-acetylglucosamine
      and N-acetylgalactosamine as acceptors, respectively. The reaction kinetics
      demonstrated that GnbG can convert 69 +/- 4 and 71 +/- 1 % of o-nitrophenyl-beta
      D-galactopyranoside into LNB and GNB, respectively. Those reactions were
      performed in a semi-preparative scale, and the synthesized disaccharides were
      purified. The maximum yield obtained for LNB was 10.7 +/- 0.2 g/l and for GNB was
      10.8 +/- 0.3 g/l. NMR spectroscopy confirmed the molecular structures of both
      carbohydrates and the absence of reaction byproducts, which also supports that
      GnbG is specific for beta1,3-glycosidic linkages. The purified sugars were
      subsequently tested for their potential prebiotic properties using Lactobacillus
      species. The results showed that LNB and GNB were fermented by the tested strains
      of L. casei, Lactobacillus rhamnosus (except L. rhamnosus strain ATCC 53103),
      Lactobacillus zeae, Lactobacillus gasseri, and Lactobacillus johnsonii. DNA
      hybridization experiments suggested that the metabolism of those disaccharides in
      9 out of 10 L. casei strains, all L. rhamnosus strains and all L. zeae strains
      tested relies upon a phospho-beta-galactosidase homologous to GnbG. The results
      presented here support the putative role of human milk oligosaccharides for
      selective enrichment of beneficial intestinal microbiota in breast-fed infants.

PMID- 27714460
TI  - Late onset postpartum psychoses.
AB  - It has been known since the eighteenth century that postpartum psychoses can
      begin several weeks after childbirth, not during the first fortnight. There are
      almost 400 non-organic episodes in the literature, starting more than 3 weeks
      after the birth; some of them are recurrent. The distinction of this disorder
      from early onset puerperal psychosis is supported by the distribution of onsets
      (which shows a steep fall after 14-15 days), survey data and the association with
      later pregnancies, not the first. Marce believed that these late onsets were
      related to the resumption of menstruation. This is a hypothesis worth
      investigating.

PMID- 27714463
TI  - Metacommunity ecology meets biogeography: effects of geographical region, spatial
      dynamics and environmental filtering on community structure in aquatic organisms.
AB  - Metacommunity patterns and underlying processes in aquatic organisms have
      typically been studied within a drainage basin. We examined variation in the
      composition of six freshwater organismal groups across various drainage basins in
      Finland. We first modelled spatial structures within each drainage basin using
      Moran eigenvector maps. Second, we partitioned variation in community structure
      among three groups of predictors using constrained ordination: (1) local
      environmental variables, (2) spatial variables, and (3) dummy variable drainage
      basin identity. Third, we examined turnover and nestedness components of multiple
      site beta diversity, and tested the best fit patterns of our datasets using the
      "elements of metacommunity structure" analysis. Our results showed that basin
      identity and local environmental variables were significant predictors of
      community structure, whereas within-basin spatial effects were typically
      negligible. In half of the organismal groups (diatoms, bryophytes, zooplankton),
      basin identity was a slightly better predictor of community structure than local
      environmental variables, whereas the opposite was true for the remaining three
      organismal groups (insects, macrophytes, fish). Both pure basin and local
      environmental fractions were, however, significant after accounting for the
      effects of the other predictor variable sets. All organismal groups exhibited
      high levels of beta diversity, which was mostly attributable to the turnover
      component. Our results showed consistent Clementsian-type metacommunity
      structures, suggesting that subgroups of species responded similarly to
      environmental factors or drainage basin limits. We conclude that aquatic
      communities across large scales are mostly determined by environmental and basin
      effects, which leads to high beta diversity and prevalence of Clementsian
      community types.

PMID- 27714464
TI  - Leaf anatomy of two reciprocally non-monophyletic mountain plants (Heliosperma
      spp.): does heritable adaptation to divergent growing sites accompany the onset
      of speciation?
AB  - Evolution is driven by natural selection, favouring individuals adapted in
      phenotypic traits to the environmental conditions at their growing site. To shed
      light on ecological and (epi-) genetically based differentiation between
      Heliosperma pusillum and Heliosperma veselskyi, two reciprocally non
      monophyletic, but morphologically and ecologically divergent species from the
      south-eastern Alps, we studied various leaf anatomical traits and investigated
      chloroplast ultrastructure in leaves of the two species grown either in their
      natural habitat or in a common garden. The alpine H. pusillum occurs in open, wet
      rock habitats, whereas its close relative H. veselskyi is restricted to dry,
      shady habitats below overhanging rocks in the montane belt. H. pusillum exhibited
      higher thickness of leaves and palisade layers as adjustments and/or adaptations
      to higher irradiance and a higher stomatal area index reflecting better water
      availability. Traits were adjusted plastically, but differed between species
      grown in a common garden, suggesting that the differentiation between the two
      species is not solely based on phenotypic plasticity but also has a genetic
      basis. Our study thus supports the hypothesis that differentiation between the
      highly interfertile species is likely driven by natural selection.

PMID- 27714467
TI  - Is the role of rhinoviruses as causative agents of pediatric community-acquired
      pneumonia over-estimated?
AB  - : The role that rhinoviruses, enteroviruses, parainfluenza viruses, coronaviruses
      and human bocavirus play in pediatric pneumonia is insufficiently studied. We
      used polymerase chain reaction (PCR) to study 9 virus groups, including 16
      different viruses or viral strains, in 56 ambulatory children with radiologically
      confirmed community-acquired pneumonia (CAP). The same tests were carried out on
      474 apparently healthy control children of the same age and sex. The mean age of
      children with CAP was 6.5 years (SD 4.2). Respiratory syncytial virus (RSV) was
      found in 19.6 % of 56 cases and in 2.1 % of 474 controls. Adenoviruses were
      present in 12.5 % of cases (0.2 % controls) and metapneumovirus and influenza A
      virus each in 10.7 % of cases (0.2 % controls). Interestingly, rhinoviruses were
      less common in cases (10.7 %) than in controls (22.4 %): odds ratio 0.36 (95%CI)
      0.15-0.87) in conditional logistic regression including 56 cases and 280 controls
      matched for age, sex and sampling month. The prevalence of parainfluenza viruses,
      enteroviruses, coronaviruses and human bocavirus were similar in both groups.
      CONCLUSION: We conclude that the role of rhinoviruses as an etiology of pediatric
      CAP has been over-estimated, mainly due to the non-controlled designs of previous
      studies. What is Known: * In non-controlled studies, rhinovirus detection has
      been common, next to respiratory syncytial virus, in children with viral
      community-acquired pneumonia (CAP). * Enteroviruses, coronaviruses and the human
      bocavirus have been found less frequently. What is New: * In this controlled
      study, rhinoviruses were detected more often in healthy controls than in children
      with CAP, and enteroviruses, coronaviruses and human bocavirus were detected
      equally often in cases and controls. * We conclude that previous studies have
      over-estimated the role of rhinoviruses in the etiology of CAP in children.

PMID- 27714466
TI  - How I do it. The pedicled temporoparietal fascia flap for skull base
      reconstruction after endonasal endoscopic approaches.
AB  - BACKGROUND: Endoscopic endonasal approaches (EEA) are an alternative for removing
      challenging nasopharyngeal or skull base lesions. In some cases, a nasoseptal
      flap (NSF) is not always available and such complex procedures may lead to
      carotid arteries exposition and/or dura mater (DM) wide opening. Meticulous
      carotid coverage and DM reconstruction are crucial for preventing early and
      delayed complications. METHOD: We propose a step-by-step description of the
      pedicled temporoparietal fascia flap (TPFF) technique, with a focus on its
      pitfalls, advantages and limits. CONCLUSION: The TPFF is a reliable flap for
      skull base reconstruction when other pedicled flaps are not available. KEY
      POINTS: 1. Reliable flap even for irradiated patients 2. CT angiography with 3D
      reconstruction as pre-operative imaging 3. Doppler ultrasound probe to draw the
      artery's trajectory on skin 4. TPFF elevation concomitantly to the endoscopic
      procedure 5. Hemicoronal incision sufficient to harvest the TPFF 6. Superficial
      dissection in a plane just beneath the hair follicles 7. Dissection plane deep to
      the fad pad to preserve the frontal branch of the facial nerve 8. Surgical
      corridor wide enough to avoid any compression of the pedicle 9. Double
      visualization to avoid any twist and Doppler control of the STA patency 10. Close
      follow-up, toilet in clinics.

PMID- 27714471
TI  - Understanding toxicology: mechanisms and applications.

PMID- 27714475
TI  - Behavior Genetics Association 46th Annual Meeting Abstracts.

PMID- 27714474
TI  - Predicting muscle fatigue: a response surface approximation based on proper
      generalized decomposition technique.
AB  - A novel technique is proposed to predict force reduction in skeletal muscle due
      to fatigue under the influence of electrical stimulus parameters and muscle
      physiological characteristics. Twelve New Zealand white rabbits were divided in
      four groups ([Formula: see text]) to obtain the active force evolution of in
      vitro Extensor Digitorum Longus muscles for an hour of repeated contractions
      under different electrical stimulation patterns. Left and right muscles were
      tested, and a total of 24 samples were used to construct a response surface based
      in the proper generalized decomposition. After the response surface development,
      one additional rabbit was used to check the predictive potential of the
      technique. This multidimensional surface takes into account not only the decay of
      the maximum repeated peak force, but also the shape evolution of each
      contraction, muscle weight, electrical input signal and stimulation protocol.
      This new approach of the fatigue simulation challenge allows to predict, inside
      the multispace surface generated, the muscle response considering other
      stimulation patterns, different tissue weight, etc.

PMID- 27714457
TI  - Identification and characterisation of Short Interspersed Nuclear Elements in the
      olive tree (Olea europaea L.) genome.
AB  - Short Interspersed Nuclear Elements (SINEs) are nonautonomous retrotransposons in
      the genome of most eukaryotic species. While SINEs have been intensively
      investigated in humans and other animal systems, SINE identification has been
      carried out only in a limited number of plant species. This lack of information
      is apparent especially in non-model plants whose genome has not been sequenced
      yet. The aim of this work was to produce a specific bioinformatics pipeline for
      analysing second generation sequence reads of a non-model species and identifying
      SINEs. We have identified, for the first time, 227 putative SINEs of the olive
      tree (Olea europaea), that constitute one of the few sets of such sequences in
      dicotyledonous species. The identified SINEs ranged from 140 to 362 bp in length
      and were characterised with regard to the occurrence of the tRNA domain in their
      sequence. The majority of identified elements resulted in single copy or very
      lowly repeated, often in association with genic sequences. Analysis of sequence
      similarity allowed us to identify two major groups of SINEs showing different
      abundances in the olive tree genome, the former with sequence similarity to SINEs
      of Scrophulariaceae and Solanaceae and the latter to SINEs of Salicaceae. A
      comparison of sequence conservation between olive SINEs and LTR retrotransposon
      families suggested that SINE expansion in the genome occurred especially in very
      ancient times, before LTR retrotransposon expansion, and presumably before the
      separation of the rosids (to which Oleaceae belong) from the Asterids. Besides
      providing data on olive SINEs, our results demonstrate the suitability of the
      pipeline employed for SINE identification. Applying this pipeline will favour
      further structural and functional analyses on these relatively unknown elements
      to be performed also in other plant species, even in the absence of a reference
      genome, and will allow establishing general evolutionary patterns for this kind
      of repeats in plants.

PMID- 27714473
TI  - Radiologists' Variation of Time to Read Across Different Procedure Types.
AB  - The workload of US radiologists has increased over the past two decades as
      measured through total annual relative value units (RVUs). This increase in RVUs
      generated suggests that radiologists' productivity has increased. However, true
      productivity (output unit per input unit; RVU per time) is at large unknown since
      actual time required to interpret and report a case is rarely recorded. In this
      study, we analyzed how the time to read a case varies between radiologists over a
      set of different procedure types by retrospectively extracting reading times from
      PACS usage logs. Specifically, we tested two hypotheses that; i) relative
      variation in time to read per procedure type increases as the median time to read
      a procedure type increases, and ii) relative rankings in terms of median reading
      speed for individual radiologists are consistent across different procedure
      types. The results that, i) a correlation of -0.25 between the coefficient of
      variation and median time to read and ii) that only 12 out of 46 radiologists had
      consistent rankings in terms of time to read across different procedure types,
      show both hypotheses to be without support. The results show that workload
      distribution will not follow any general rule for a radiologist across all
      procedures or a general rule for a specific procedure across many readers. Rather
      the findings suggest that improved overall practice efficiency can be achieved
      only by taking into account radiologists' individual productivity per procedure
      type when distributing unread cases.

PMID- 27714478
TI  - Clinically applied procedures for human ovarian tissue cryopreservation result in
      different levels of efficacy and efficiency.
AB  - PURPOSE: Different protocols are being used worldwide for the cryopreservation of
      human ovarian tissue for fertility preservation purposes. The efficiency and
      efficacy of the majority of these protocols has not been extensively evaluated,
      possibly resulting in sub-optimally cryopreserved ovarian tissue. To address the
      impact of this issue, we assessed the effects of two clinically successful human
      ovarian tissue slow-freezing cryopreservation procedures on the quality of the
      cryopreserved tissue. METHODS: To differentiate between cryopreservation (C)
      versus thawing (T) related effects, four combinations of these two (A and B) very
      different cryopreservation/thawing protocols (ACAT, ACBT, BCAT, BCBT) were
      studied. Before and after cryopreservation and thawing, the percentage of living
      and morphologically normal follicles, as well as the overall tissue viability,
      was assessed. RESULTS: Our experiments revealed that the choice of the
      cryopreservation protocol noticeably affected the overall tissue viability and
      percentage of living follicles, with a higher viability after protocol BC when
      compared to AC. No statistically significant differences in tissue viability were
      observed between the two thawing protocols, but thawing protocol BT required
      considerably more human effort and materials than thawing protocol AT. Tissue
      morphology was best retained using the BCAT combination. CONCLUSION: Our results
      indicate that extensive and systematical evaluation of clinically used protocols
      is warranted.

PMID- 27714476
TI  - Cardioprotection: Where to from here?
AB  - The size of the myocardial infarction remains an important therapeutic target,
      because heart attack size correlates with mortality and heart failure. In this
      era, myocardial infarct size is reduced primarily by timely reperfusion of the
      infarct related coronary artery. Whereas numerous pre-clinical studies have shown
      that certain pharmacologic agents and therapeutic maneuvers reduce myocardial
      infarction size greater than reperfusion alone, very few of these therapies have
      translated to successful clinical trials or standard clinical use. In this review
      we discuss both the recent successes as well as recent disappointments, and
      describe some of the newer potential therapies from the preclinical literature
      that have not yet been tested in clinical trials.

PMID- 27714472
TI  - Function-preserving gastrectomy based on the sentinel node concept in early
      gastric cancer.
AB  - Recent meta-analyses and a prospective multicenter trial of sentinel node (SN)
      mapping in early gastric cancer have demonstrated acceptable SN detection rates
      and accuracy of determination of lymph node status. SN mapping may play a key
      role in obtaining individual metastatic information. It also allows modification
      of surgical procedures, including function-preserving gastrectomy in patients
      with early gastric cancer. A dual-tracer method that uses radioactive colloids
      and blue dye is currently considered the most reliable method for the stable
      detection of SNs in patients with early gastric cancer. New technologies, such as
      indocyanine green infrared or fluorescence imaging, are also useful for accurate
      SN mapping in gastric cancer. Theoretically, laparoscopic function-preserving
      gastrectomy, including partial resection, proximal gastrectomy, segmental
      gastrectomy, and pylorus-preserving gastrectomy, is feasible in early gastric
      cancer when the SN(s) is/are nonmetastatic. Our study group conducted a
      multicenter prospective trial in Japan to evaluate function-preserving
      gastrectomy with SN mapping for long-term survival and patient quality of life.
      Non-exposed endoscopic wall-inversion surgery (NEWS) is a new technique for
      treating gastric cancer with partial resection involving full-thickness resection
      with endoscopy and laparoscopic surgery without transluminal access. The
      combination of NEWS and SN biopsy is expected to be a promising, minimally
      invasive, function-preserving surgery that is ideal for cases of cN0 early
      gastric cancer.

PMID- 27714465
TI  - IgA nephropathy with presentation of nephrotic syndrome at onset in children.
AB  - BACKGROUND: Despite a low incidence, nephrotic syndrome (NS) can present with IgA
      nephropathy (IgAN). The clinical characteristics and long-term outcomes of
      pediatric patients with IgAN presenting with NS (NS-IgAN) at onset have not been
      fully elucidated. METHODS: We retrospectively analyzed 426 patients, and compared
      clinical and pathological (Oxford) findings between those with NS-IgAN and those
      with non-NS-IgAN. RESULTS: Among 426 patients, 30 (7.0 %) had NS-IgAN. Logistic
      analyses showed that male sex (OR: 7.6, p = 0.0002), M1 (OR: 10.3, p = 0.002),
      and E1 (OR: 15.2, p = 0.0001) were significantly related to NS. The mean
      observation period was 6.2 +/- 3.2 years. Although NS-IgAN was associated with
      significantly lower renal survival than non-NS-IgAN according to Kaplan-Meier
      analysis (p = 0.02), renal survival of NS-IgAN was good (92.4 % at 10 years). The
      most significant prognostic factor for renal survival was remission of
      proteinuria after treatment, and NS at onset is also a significant prognostic
      factor for renal survival after adjusting for remission of proteinuria. Twenty
      children with NS-IgAN were treated with prednisolone alone, or prednisolone and
      immunosuppressant. Remission of proteinuria occurred in 21 patients. Three cases
      of NS-IgAN progressed to stage III-V chronic kidney disease at the most recent
      observation. They all demonstrated heavy proteinuria after the 2-year initial
      treatment. The significant factor for persistent proteinuria at 5 years was S1 in
      NS-IgAN. CONCLUSIONS: The most significant factor for renal survival was
      responsiveness to treatment, not NS itself. As modifiable acute lesions are the
      dominant pathological findings in NS-IgAN, histological improvements achieved by
      appropriate treatments can result in a favorable prognosis.

PMID- 27714481
TI  - TP53 and CDKN1A mutation analysis in families with Li-Fraumeni and Li-Fraumeni
      like syndromes.
AB  - Li-Fraumeni and Li-Fraumeni like syndromes (LFS/LFL) represent rare cancer-prone
      conditions associated mostly with sarcomas, breast cancer, brain tumors, and
      adrenocortical carcinomas. TP53 germline mutations are present in up to 80 % of
      families with classic Li-Fraumeni syndrome, and in 20-60 % of families with Li
      Fraumeni like phenotypes. The frequency of LFS/LFL families with no TP53
      mutations detected suggests the involvement of other genes in the syndrome. In
      this study, we searched for mutations in TP53 in 39 probands from families with
      criteria for LFS/LFL. We also searched for mutations in the gene encoding the
      main mediator of p53 in cell cycle arrest, CDKN1A/p21, in all patients with no
      mutations in TP53. Eight probands carried germline disease-causing mutations in
      TP53: six missense mutations and two partial gene deletions. No mutations in
      CDKN1A coding region were detected. TP53 partial deletions in our cohort
      represented 25 % (2/8) of the mutations found, a much higher frequency than
      usually reported, emphasizing the need to search for TP53 rearrangements in
      patients with LFS/LFL phenotypes. Two benign tumors were detected in two TP53
      mutation carriers: an adrenocortical adenoma and a neurofibroma, which raises a
      question about the possible implication of TP53 mutations on the development of
      such lesions.

PMID- 27714469
TI  - Ambulatory 24-h ECG monitoring and cardiovascular autonomic assessment for the
      screening of silent myocardial ischemia in elderly type 2 diabetic hypertensive
      patients.
AB  - The aim of the study was to evaluate the usefulness of Holter monitoring for the
      detection of silent myocardial ischemia (SMI) in elderly type 2 diabetic patients
      with hypertension and the possible relationship between SMI and cardiovascular
      autonomic neuropathy (CAN). Two hundred and forty-three asymptomatic outpatients,
      aged 65-75 years, with type 2 diabetes and essential hypertension underwent 24-h
      ECG monitoring and 5 tests for the evaluation of both parasympathetic (heart rate
      variability, response to breath deeping, and Valsalva manoeuvre) and sympathetic
      (cold pressor test and orthostatic hypotension test) autonomic function. A total
      of 518 asymptomatic episodes of ST depression during Holter monitoring indicative
      of SMI were detected in 51 of the 243 studied patients (20.9 %). None of the
      patients with ST depression episodes exhibited a normal response to at least one
      of the evaluated autonomic function tests, whereas 22 of the 192 patients without
      ST changes (11.4 %) exhibited a normal response to all tests. Abnormality in both
      parasympathetic and sympathetic function test responses was found in 94.1 % of
      patients with ST depression episodes vs 26.1 % of those without ST changes (P <
      0.001). Statistical evaluation of the relationship between the abnormal response
      to single autonomic function test and episodes of ST depression was highly
      significant for all the 5 tests (P < 0.001). These results indicate that: (a)
      Holter monitoring enables to detect ST segment changes indicative of SMI in 20.9
      % of elderly diabetic patients with hypertension; (b) the presence of autonomic
      cardiac dysfunction in these patients suggests a role of diabetic neuropathy in
      the pathogenesis of SMI; and

PMID- 27714479
TI  - Clinical pregnancy rate following frozen embryo transfer is higher with
      blastocysts vitrified on day 5 than on day 6.
AB  - PURPOSE: The aim of this study was to compare the pregnancy rates between good
      quality blastocysts vitrified on day 6 versus blastocysts vitrified on day 5
      after fertilization. METHODS: This is a retrospective cohort study of 791 freeze
      thaw cycles of blastocysts vitrified either on day 5 or on day 6 and transferred
      between January 2012 and October 2015. Five hundred and thirty-seven cycles
      included blastocysts vitrified on day 5, and 254 cycles included blastocysts
      vitrified on day 6. RESULTS: The age of the patients and the proportion of
      embryos that survived the thawing process were comparable between the two groups.
      More good quality embryos were transferred in the group in which blastocysts were
      vitrified on day 6 (1.2 vs. 1.3, p = 0.005), but the clinical pregnancy rate (44
      vs. 33 %, p = 0.002) and the ongoing pregnancy rate (41 vs. 28 %, p < 0.001) were
      higher in the group in which blastocysts were vitrified on day 5. Multivariate
      regression analysis adjusting for patient's age, number of good quality embryos
      transferred (>=3BB), and treatment protocol demonstrated that the day 6 vitrified
      group had a significantly lower clinical pregnancy rate compared to the day 5
      vitrified group (OR 0.54, 95 % CI 0.38-0.76). CONCLUSIONS: The clinical pregnancy
      rate following frozen embryo transfer is significantly lower with blastocysts
      vitrified on day 6 compared to blastocysts vitrified on day 5.

PMID- 27714477
TI  - Targeted, Site-specific quantitation of N- and O-glycopeptides using 18O-labeling
      and product ion based mass spectrometry.
AB  - The site-specific quantitation of N- and O-glycosylation is vital to
      understanding the function(s) of different glycans expressed at a given site of a
      protein under physiological and disease conditions. Most commonly used precursor
      ion intensity based quantification method is less accurate and other labeled
      methods are expensive and require enrichment of glycopeptides. Here, we used
      glycopeptide product (y and Y0) ions and 18O-labeling of C-terminal carboxyl
      group as a strategy to obtain quantitative information about fold-change and
      relative abundance of most of the glycoforms attached to the glycopeptides. As a
      proof of concept, the accuracy and robustness of this targeted, relative
      quantification LC-MS method was demonstrated using Rituximab. Furthermore, the N
      glycopeptide quantification results were compared with a biosimilar of Rituximab
      and validated with quantitative data obtained from 2-AB-UHPLC-FL method. We
      further demonstrated the intensity fold-change and relative abundance of 46
      unique N- and O-glycopeptides and aglycopeptides from innovator and biosimilar
      samples of Etanercept using both the normal-MS and product ion based
      quantitation. The results showed a very similar site-specific expression of N-
      and O-glycopeptides between the samples but with subtle differences.
      Interestingly, we have also been able to quantify macro-heterogeneity of all N-
      and O-glycopetides of Etanercept. In addition to applications in biotherapeutics,
      the developed method can also be used for site-specific quantitation of N- and O
      glycopeptides and aglycopeptides of glycoproteins with known glycosylation
      pattern.

PMID- 27714484
TI  - Reliability and Validity of a Newly Developed Measure of Citizenship Among
      Persons with Mental Illnesses.
AB  - Following development of a 46-item of measure citizenship, a framework for
      supporting the full membership in society of persons with mental illness, this
      study tested the measure's reliability and validity. 110 persons from a mental
      health center completed a questionnaire packet containing the citizenship measure
      and other measures to assess internal consistency and validity of the citizenship
      instrument. Correlation matrices were examined for associations between the
      citizenship instrument and other measures. Stepwise regression examines
      demographic factors, sense of community, and social capital as predictors of
      citizenship, recovery, and well-being. Analyses revealed that the measure is
      psychometrically sound. The measure captures subjective information about the
      degree to which individuals experience rights, sense of belonging, and other
      factors associated with community membership that have been previously difficult
      to assess. The measure establishes a platform for interventions to support the
      full participation in society of persons with mental illnesses.

PMID- 27714483
TI  - Developmental Trajectories of Youth Conduct Problems: Testing Later Development
      and Related Outcomes in a 12-Year Period.
AB  - Developmental heterogeneity of youth conduct problems has been widely assumed,
      leading to the identification of distinctive groups at particular risk of more
      serious problems later in development. The present study intends to expand the
      main results of a prior study focused on identifying developmental trajectories
      of conduct problems (Stable-low, Stable-high, and Decreasing), by analyzing their
      developmental course and related outcomes during middle/late adolescence and
      early adulthood. Two follow-up studies were conducted 10 and 12 years after the
      initial study with 115 and 122 youths respectively (mean = 17.29 and 19.18).
      Overall results underline that the Early-onset persistent group showed the
      highest risk-profile; the Childhood-limited group revealed a moderate level of
      later maladjustment; and the Adolescence-onset group, currently identified,
      showed a significant peak of risk particularly in middle/late adolescence. These
      findings provide a more comprehensive representation of youth conduct problems,
      and open new means of discussion in terms of preventive intervention.

PMID- 27714470
TI  - Oak protein profile alterations upon root colonization by an ectomycorrhizal
      fungus.
AB  - An increased knowledge on the real impacts of ectomycorrhizal symbiosis in forest
      species is needed to optimize forest sustainable productivity and thus to improve
      forest services and their capacity to act as carbon sinks. In this study, we
      investigated the response of an oak species to ectomycorrhizae formation using a
      proteomics approach complemented by biochemical analysis of carbohydrate levels.
      Comparative proteome analysis between mycorrhizal and nonmycorrhizal cork oak
      plants revealed no differences at the foliar level. However, the protein profile
      of 34 unique oak proteins was altered in the roots. Consistent with the results
      of the biochemical analysis, the proteome analysis of the mycorrhizal roots
      suggests a decreasing utilization of sucrose for the metabolic activity of
      mycorrhizal roots which is consistent with an increased allocation of
      carbohydrates from the plant to the fungus in order to sustain the symbiosis. In
      addition, a promotion of protein unfolding mechanisms, attenuation of defense
      reactions, increased nutrient mobilization from the plant-fungus interface (N and
      P), as well as cytoskeleton rearrangements and induction of plant cell wall
      loosening for fungal root accommodation in colonized roots are also suggested by
      the results. The suggested improvement in root capacity to take up nutrients
      accompanied by an increase of root biomass without apparent changes in
      aboveground biomass strongly re-enforces the potential of mycorrhizal inoculation
      to improve cork oak forest resistance capacity to cope with coming climate
      change.

PMID- 27714480
TI  - Impact of spinal cord compression from intradural and epidural spinal tumors on
      perioperative symptoms-implications for surgical decision making.
AB  - Spinal cord or cauda equina compression (SCC) is an increasing challenge in
      clinical oncology due to a higher prevalence of long-term cancer survivors. Our
      aim was to determine the clinical relevance of SCC regarding patient outcome
      depending on different tumor entities and their anatomical localization
      (extradural/intradural/intramedullary). We retrospectively analyzed 230 patients
      surgically treated for SCC. Preoperative status for pain and neurological
      impairment were correlated to the degree of compression, tumor location, and
      early as well as short-term follow-up outcome parameters. Interestingly, we did
      not observe any differences between intradural-extramedullary compared to
      extradural tumors. Unilaterally localized tumors were likely to present with pain
      (72.9 %, p < 0.01), whereas concentric growth was associated with motor deficits
      (41.0 %, p < 0.01, as primary symptom, 49.3 % on admission, p < 0.05). In
      concentric tumors, the pain pattern was diffuse (40.5 % vs. 17.5 in unilateral
      disease, p < 0.01), whereas unilateral tumors resulted in localized pain (61.4 %
      local axial or radicular, p < 0.01). Diffuse pain, patients without a sensory or
      motor deficit, progressive disease, cervical localization, and a higher degree of
      stenosis were identified as beneficial for an early improvement in pain (p <
      0.05). Notably, 29 % of patients with unchanged pain and 30.8 % with unchanged
      neurologic function at day 7 postoperative improved during follow-up (p < 0.001).
      Our data demonstrate that the preoperative tumor anatomy in patients with SCC was
      closely related to their presenting symptoms and early clinical outcome. The
      detailed analysis elucidates the biology of SCC and might thereby aid in
      determining which patients will benefit from surgery.

PMID- 27714482
TI  - Biosimilars in rheumatic diseases: structural and functional variability that may
      impact clinical and regulatory decisions.
AB  - Biologics as therapeutic interventions for human disease represent both a
      distinctly modern novelty and an echo of ancient, or at least old, medical
      practice. The similarity lies in the sense that in both the synthetic effort
      occurs in living organisms (an extract of a plant, animal tissue, or a cell
      culture) while the difference is apparent in the bioengineering required in
      modern methods and the corresponding flexibility to customize the therapeutic
      product. Although the concept of looking to living systems as a source of
      medically useful compounds either for research or for actual patient care has
      never vanished, the development of biochemistry and advances in medicinal
      chemistry made production by total synthesis the standard for a safe, reliable,
      and commercial drug production at sufficient scale. In this interval was where
      much of the modern apparatus for approving medical therapies came to be
      developed, and as such, the most proper extension of the regulatory regime to
      modern biologics is not entirely obvious. In particular, the notion of generics
      for off-patent conventional pharmaceuticals and their role in the marketplace
      with respect to increasing the accessibility of treatment is not congruent with
      the relationship between what are known as biosimilars and off-patent originating
      biologics. In this article, we review elements of the scientific basis for
      challenges in the production, use, and regulation of biosimilars. In light of
      these advances, we propose suggestions to modify constraints on biosimilar
      regulations in the interest of patient care and access to therapies.

PMID- 27714468
TI  - Disc associating axial pain were indicated by PLL resection in ACDF surgery.
AB  - PURPOSE: The generation and tissue origination of disc-associated axial pain is
      still under exploration. This study was performed to evaluate disc-associated
      axial pain and to explore whether it originates in the disc or its surrounding
      components. METHODS: A 6-year series of 88 single-level Smith-Robinson disc and
      posterior longitudinal ligament (PLL) resections performed to treat single-level
      cervical spondylotic myelopathy was retrospectively examined. All single-level
      anterior disc decompressions were performed under local infiltration anesthesia;
      the PLL was not anesthetized to avoid cervical cord block. The patients were
      grouped by disc level. The centered foci of the pain localization were
      subjectively recorded before, during, and after the operation. Radiological
      examinations (plain X-ray, computed tomography, and magnetic resonance imaging)
      were performed before and after the operation to diagnose the compression and
      evaluate the decompression. RESULTS: All 88 patients who underwent single-level
      PLL resection had no intraoperative pain responses except during resection of the
      PLL. Their provoked pain responses were similar to their familiar pain responses.
      The axial pain disappeared postoperatively. Complications developed in six
      patients (6.8 %). All patients recovered well, and the absence of the axial pain
      was maintained at the 12-month follow-up. CONCLUSIONS: Preoperative axial pain
      due to single-level disc protrusion was triggered and aggravated only during PLL
      resection and disappeared postoperatively. This implies that the intervertebral
      PLL could be the site of origination of axial pain. Axial pain from the PLL at
      different disc levels had different distributions.

PMID- 27714488
TI  - Editorial note.

PMID- 27714455
TI  - Genetic basis of hepatitis virus-associated hepatocellular carcinoma: linkage
      between infection, inflammation, and tumorigenesis.
AB  - Hepatitis virus infection is a leading cause of chronic liver disease, including
      cirrhosis and hepatocellular carcinoma (HCC). Although anti-viral therapies
      against hepatitis B virus (HBV) and hepatitis C virus (HCV) have dramatically
      progressed during the past decade, the estimated number of people chronically
      infected with HBV and/or HCV is ~370 million, and hepatitis virus-associated
      hepatocarcinogenesis is a serious health concern worldwide. Understanding the
      mechanism of virus-associated carcinogenesis is crucial toward both treatment and
      prevention, and the recently developed whole genome/exome sequencing analysis
      using next-generation sequencing technologies has contributed to unveiling the
      landscape of genetic and epigenetic aberrations in not only tumor tissues but
      also the background liver tissues underlying chronic liver damage caused by
      hepatitis virus infection. Several major mechanisms underlie the genetic and
      epigenetic aberrations in the hepatitis virus-infected liver, such as the
      generation of reactive oxidative stress, ectopic expression of DNA mutator
      enzymes, and dysfunction of the DNA repair system. In addition, direct oncogenic
      effects of hepatitis virus, represented by the integration of HBV-DNA, are
      observed in infected hepatocytes. Elucidating the whole picture of genetic and
      epigenetic alterations, as well as the mechanisms of tumorigenesis, will
      facilitate the development of efficient treatment and prevention strategies for
      hepatitis virus-associated HCC.

PMID- 27714486
TI  - Optimized workflow and imaging protocols for whole-body oncologic PET/MRI.
AB  - Although PET/MRI has the advantages of a simultaneous acquisition of PET and MRI,
      high soft-tissue contrast of the MRI images, and reduction of radiation exposure,
      its low profitability and long acquisition time are significant problems in
      clinical settings. Thus, MRI protocols that meet oncological purposes need to be
      used in order to reduce examination time while securing detectability. Currently,
      half-Fourier acquisition single-shot turbo spin echo and 3D-T1 volumetric
      interpolated breath-hold examination may be the most commonly used sequences for
      whole-body imaging due to their shorter acquisition time and higher diagnostic
      accuracy. Although there have been several reports that adding diffusion weighted
      image (DWI) to PET/MRI protocol has had no effect on tumor detection to date, in
      cases of liver, kidney, bladder, and prostate cancer, the use of DWI may be
      beneficial in detecting lesions. Another possible option is to scan each region
      with different MRI sequences instead of scanning the whole body using one
      sequence continuously. We herein report a workflow and imaging protocols for
      whole-body oncologic PET/MRI using an integrated system in the clinical routine,
      designed for the detection, for example by cancer screening, of metastatic
      lesions, in order to help future users optimize their workflow and imaging
      protocols.

PMID- 27714487
TI  - Neuroimaging findings of Zika virus infection: a review article.
AB  - Zika virus (ZIKV) is an arbovirus from the Flaviviridae family. It is usually
      transmitted by mosquito bite. There have been no reports of severe symptoms
      caused by ZIKV infection up until the last few years. In October 2013 an outbreak
      was reported in French Polynesia with severe neurological complications in some
      affected cases. In November 2015, the Ministry of Health of Brazil attributed the
      increased number of neonatal microcephaly cases in northeastern Brazil to
      congenital ZIKV infection. The rapid spread of the virus convinced the World
      Health Organization to announce ZIKV infection as a "Public Health Emergency of
      International Concern" in February 2016. The main neuroimaging findings in
      congenital ZIKV infection include microcephaly which is the hallmark of the
      disease, other malformations of cortical development (e.g., lissencephaly,
      heterotopia, etc.), parenchymal calcifications, unilateral or bilateral
      ventriculomegaly, enlarged extra-axial CSF spaces, dysgenesis of the corpus
      callosum, agenesis of the cavum septum pellucidum, cerebellar and brainstem
      hypoplasia, and ocular abnormalities. ZIKV infection may also cause Guillain
      Barre syndrome and acute disseminated encephalomyelitis in adults. Familiarity
      with neuroimaging findings of congenital and acquired ZIKV infection is crucial
      to suspect this disease in residents of endemic regions and travelers to these
      areas.

PMID- 27714489
TI  - Novel interaction between CCR4 and CAF1 in rice CCR4-NOT deadenylase complex.
AB  - KEY MESSAGE: Rice is an important crop in the world. However, little is known
      about rice mRNA deadenylation, which is an important regulation step of gene
      expression at the post-transcriptional level. The CCR4-NOT1 complex contains two
      key components, CCR4 and CAF1, which are the main cytoplasmic deadenylases in
      eukaryotic cells. In yeast and humans, CCR4 can interact with CAF1 via its N
      terminal LRR domain. However, no CCR4 protein containing N-terminal LRR motifs
      have been found in plants. In this manuscript, we demonstrate a novel pattern of
      interaction between OsCCR4 and OsCAF1 in the rice CCR4-NOT complex, and that
      OsCAF1 acts as a bridge between OsCCR4 and OsNOT1 in this complex. Our results
      revealed that the Mynd-like domain at the N-terminus of rice CCR4 proteins and
      the PXLXP motif at the rice CAF1 N-terminus play critical roles in OsCCR4-OsCAF1
      interaction. Deadenylation, also called poly(A) tail shortening, is the first
      rate-limiting step in general cytoplasmic mRNA degradation in eukaryotic cells.
      Carbon catabolite repressor (CCR)4 and CCR4-associated factor (CAF)1 in the CCR4
      NOT complex function in mRNA poly(A) tail shortening. CCR4s contain N-terminal
      leucine-rich repeat (LRR) motifs that interact with CAF1s in yeast, fruit fly and
      mammals. In silico analysis has not identified any plant CCR4 proteins that
      contain LRR motifs. Here, two rice CCR4 homologous genes, OsCCR4a and OsCCR4b,
      were identified. The isolated recombinant exonuclease-endonuclease-phosphatase
      domain of OsCCR4a and OsCCR4b exhibited 3'-5' exonuclease activity in vitro, and
      point mutation of a catalytic residue in this domain disrupted the deadenylase
      activity. Both OsCCR4a and OsCCR4b fluorescent fusion proteins were localized in
      the rice cytoplasm and nucleus, and both associated with processing bodies via
      their N-terminus. Binding analyses showed that OsCCR4a and OsCCR4b directly
      interacted with three rice CAF1 family members: OsCAF1A, OsCAF1G and OsCAF1H. The
      zf-MYND-like domain at the N terminus of rice CCR4 and the PXLXP motif of rice
      CAF1 play critical roles in OsCCR4-OsCAF1 interaction. OsCAF1 proteins, but not
      OsCCR4 proteins, can interact with the MIG4G domain of rice OsNOT1. Our studies
      thus reveal a hitherto undiscovered novel interaction pattern that connects
      OsCCR4 and OsCAF1 in the rice CCR4-NOT complex.

PMID- 27714485
TI  - A Pilot Study of Fragile X Syndrome Screening in Pregnant Women and Women
      Planning Pregnancy: Implementation, Acceptance, Awareness, and Geographic
      Factors.
AB  - We report herein results of a study performed in the Balearic Islands which had
      the following goals: 1) Determine the proportion of pregnant or non-pregnant
      women planning pregnancy, who would choose to undergo a screening test for
      Fragile X Syndrome (FXS), if it is accompanied by the appropriate information; 2)
      Assess satisfaction and any increase in stress among women who participate in
      screening; 3) Collect epidemiological information about the incidence of the
      disease in our population; and 4) Collect demographic and health history data and
      assess participants' awareness of the disease. Screening was performed on 3,731
      pregnant and non-pregnant women of childbearing age and the results indicate: a
      very high voluntary rate of participation; a high level of self-reported
      satisfaction and low levels of stress because of the test; a very high incidence
      of premutation (1/106) in our population; and a low level of awareness about the
      existence of FXS (25 %). Additional findings indicate no significant correlation
      between self-reported health history and premutation detection, and the high
      premutation incidence does not seem to be specific to the indigenous Balearic
      population. Based on these results, we discuss the pros and cons of an
      implementation of preconception and pregnant women screening for FXS within a
      public health screening program.

PMID- 27714491
TI  - Early Sex Work Initiation and Violence against Female Sex Workers in Mombasa,
      Kenya.
AB  - Between 20 and 40 % of female sex workers (FSWs) began sex work before age 18.
      Little is known concerning whether early initiation of sex work impacts later
      experiences in adulthood, including violence victimization. This paper examines
      the relationship between early initiation of sex work and violence victimization
      during adulthood. The sample included 816 FSWs in Mombasa, Kenya, recruited from
      HIV prevention drop-in centers who were 18 years or older and moderate-risk
      drinkers. Early initiation was defined as beginning sex work at 17 or younger.
      Logistic regression modeled recent violence as a function of early initiation,
      adjusting for drop-in center, age, education, HIV status, supporting others, and
      childhood abuse. Twenty percent of the sample reported early initiation of sex
      work. Although both early initiators and other FSWs reported commonly
      experiencing recent violence, early initiators were significantly more likely to
      experience recent physical and sexual violence and verbal abuse from paying
      partners. Early initiation was not associated with physical or sexual violence
      from non-paying partners. Many FSWs begin sex work before age 18. Effective
      interventions focused on preventing this are needed. In addition, interventions
      are needed to prevent violence against all FSWs, in particular, those who
      initiated sex work during childhood or adolescence.

PMID- 27714492
TI  - Carcass characteristics and meat quality of lambs fed babassu cake (Orbignya
      speciosa) as a replacement for elephant grass silage.
AB  - The study aimed to evaluate the effect of the partial replacement of elephant
      grass silage with babassu cake (Orbignya speciosa) on the carcass characteristics
      and meat quality of feedlot lambs. Forty-five castrated male Santa Ines sheep
      (19.08 +/- 0.41 kg) approximately 4 months old were distributed in a completely
      randomized design, with five treatments 0.0, 12.5, 25.0, 37.5 and 50 % (%DM)
      replacement of babassu cake with silage forming isoproteic diets formulated at a
      ratio of 40 % roughage to 60 % concentrate. All of the studied animals were
      slaughtered at the end of the experiment. The liver weights and yields increased
      with the inclusion of babassu cake. The weight of the shoulder increased from
      2.31 to 2.61 kg, while the loin yield decreased from 7.38 to 6.64 % with the
      inclusion of babassu cake, both linearly. The body length, thoracic perimeter,
      rump perimeter and carcass compactness index showed high and positive
      correlations with the hot and cold carcass weights. The myofibrillar
      fragmentation index decreased linearly as a function of the inclusion level of
      babassu cake, but other quality variables were not affected. The replacement of
      up to 50 % of the elephant grass silage with babassu cake in the diet of lambs
      does not cause negative effects on carcass characteristics or meat quality.

PMID- 27714493
TI  - Improved pose and affinity predictions using different protocols tailored on the
      basis of data availability.
AB  - The D3R 2015 grand drug design challenge provided a set of blinded challenges for
      evaluating the applicability of our protocols for pose and affinity prediction.
      In the present study, we report the application of two different strategies for
      the two D3R protein targets HSP90 and MAP4K4. HSP90 is a well-studied target
      system with numerous co-crystal structures and SAR data. Furthermore the D3R
      HSP90 test compounds showed high structural similarity to existing HSP90
      inhibitors in BindingDB. Thus, we adopted an integrated docking and scoring
      approach involving a combination of both pharmacophoric and heavy atom similarity
      alignments, local minimization and quantitative structure activity relationships
      modeling, resulting in the reasonable prediction of pose [with the root mean
      square deviation (RMSD) values of 1.75 A for mean pose 1, 1.417 A for the mean
      best pose and 1.85 A for the mean all poses] and affinity (ROC AUC = 0.702 at 7.5
      pIC50 cut-off and R = 0.45 for 180 compounds). The second protein, MAP4K4,
      represents a novel system with limited SAR and co-crystal structure data and
      little structural similarity of the D3R MAP4K4 test compounds to known MAP4K4
      ligands. For this system, we implemented an exhaustive pose and affinity
      prediction protocol involving docking and scoring using the PLANTS software which
      considers side chain flexibility together with protein-ligand fingerprints
      analysis assisting in pose prioritization. This protocol through fares poorly in
      pose prediction (with the RMSD values of 4.346 A for mean pose 1, 4.69 A for mean
      best pose and 4.75 A for mean all poses) and produced reasonable affinity
      prediction (AUC = 0.728 at 7.5 pIC50 cut-off and R = 0.67 for 18 compounds,
      ranked 1st among 80 submissions).

PMID- 27714490
TI  - A genetic genomics-expression approach reveals components of the molecular
      mechanisms beyond the cell wall that underlie peach fruit woolliness due to cold
      storage.
AB  - Peach fruits subjected to prolonged cold storage (CS) to delay decay and over
      ripening often develop a form of chilling injury (CI) called mealiness/woolliness
      (WLT), a flesh textural disorder characterized by lack of juiciness. Transcript
      profiles were analyzed after different lengths of CS and subsequent shelf life
      ripening (SLR) in pools of fruits from siblings of the Pop-DG population with
      contrasting sensitivity to develop WLT. This was followed by quantitative PCR on
      pools and individual lines of the Pop-DG population to validate and extend the
      microarray results. Relative tolerance to WLT development during SLR was related
      to the fruit's ability to recover from cold and the reactivation of normal
      ripening, processes that are probably regulated by transcription factors involved
      in stress protection, stress recovery and induction of ripening. Furthermore, our
      results showed that altered ripening in WLT fruits during shelf life is probably
      due, in part, to cold-induced desynchronization of the ripening program involving
      ethylene and auxin hormonal regulation of metabolism and cell wall. In addition,
      we found strong correlation between expression of RNA translation and protein
      assembly genes and the visual injury symptoms.

PMID- 27714495
TI  - Molecular and biological properties of an endornavirus infecting winged bean
      (Psophocarpus tetragonolobus).
AB  - A double-stranded RNA (dsRNA) of approximately 15 kbp was isolated from
      asymptomatic winged bean (Psophocarpus tetragonolobus) plants. The size of the
      dsRNA, together with results of RT-PCR testing, suggested that it was the
      replicative form of a plant endornavirus. Cloning, sequencing, and sequence
      analyses confirmed the endornavirus nature of the dsRNA. Conserved motifs typical
      for endornaviruses were identified and their amino acid sequences compared with
      those of selected endornaviruses. Phylogenetic analyses revealed a close
      relationship with Bell pepper endornavirus, Phaseolus vulgaris endornavirus 2,
      and Hot pepper endornavirus. The dsRNA was present in most P. tetragonolobus
      genotypes tested. The virus was provisionally named Winged bean endornavirus 1
      (WBEV-1).

PMID- 27714494
TI  - Role of R292K mutation in influenza H7N9 neuraminidase toward oseltamivir
      susceptibility: MD and MM/PB(GB)SA study.
AB  - The H7N9 avian influenza virus is a novel re-assortment from at least four
      different strains of virus. Neuraminidase, which is a glycoprotein on the surface
      membrane, has been the target for drug treatment. However, some H7N9 strains that
      have been isolated from patient after drug treatment have a R292K mutation in
      neuraminidase. This substitution was found to facilitate drug resistance using
      protein- and virus- assays, in particular it gave a high resistance to the most
      commonly used drug, oseltamivir. The aim of this research is to understand the
      source of oseltamivir resistance using MD simulations and the MM/PB(GB)SA binding
      free energy approaches. Both methods can predict the reduced susceptibility of
      oseltamivir in good agreement to the IC 50 binding energy, although MM/GBSA
      underestimates this prediction compared to the MM/PBSA calculation. Electrostatic
      interaction is the main contribution for oseltamivir binding in terms of both
      interaction and solvation. We found that the source of the drug resistance is a
      decrease in the binding interaction combined with the reduction of the
      dehydration penalty. The smaller K292 mutated residue has a larger binding pocket
      cavity compared to the wild-type resulting in the loss of drug carboxylate-K292
      hydrogen bonding and an increased accessibility for water molecules around the
      K292 mutated residue. In addition, oseltamivir does not bind well to the R292K
      mutant complex as shown by the high degree of fluctuation in ligand RMSD during
      the simulation and the change in angular distribution of bulky side chain groups.

PMID- 27714496
TI  - Community- and hospital-acquired infections with oseltamivir- and peramivir
      resistant influenza A(H1N1)pdm09 viruses during the 2015-2016 season in Japan.
AB  - We report five cases of community- and hospital-acquired infections with
      oseltamivir- and peramivir-resistant A(H1N1)pdm09 viruses possessing the
      neuraminidase (NA) H275Y mutation during January-February 2016 in Japan. One case
      was hospitalized and was receiving oseltamivir for prophylaxis. The remaining
      four cases were not taking antiviral drugs at the time of sampling. These cases
      were geographically distant and epidemiologically unrelated. The five viruses
      showed ~300-fold rise in IC50 values against oseltamivir and peramivir, defined
      as highly reduced inhibition according to the WHO definition. Overall, the
      prevalence of the H275Y A(H1N1)pdm09 viruses was 1.8 % (5/282). The resistant
      viruses possessed the V241I, N369 K, and N386 K substitutions in the NA that have
      been previously reported among A(H1N1)pdm09 to alter transmission fitness.
      Analysis of Michaelis constant (Km) revealed that two of the isolates had reduced
      NA affinity to MUNANA, while the other three isolates displayed a slightly
      decreased affinity compared to the sensitive viruses. Further studies are needed
      to monitor the community spread of resistant viruses and to assess their
      transmissibility.

PMID- 27714497
TI  - Mechanisms of ear trauma and reconstructive techniques in 105 consecutive
      patients.
AB  - Acquired auricular deformities may diminish facial esthetics and cause
      psychological distress. The aim of this article is to provide an overview of the
      type of injuries and applied reconstructive techniques in a large academic
      hospital in The Netherlands. A retrospective chart review was conducted for the
      last 105 patients who underwent auricular reconstruction for an acquired
      deformity. Data concerning gender, affected side, cause of injury, anatomical
      region, the previous and further surgeries, type of cartilage, and skin cover
      used were collected and analyzed. 105 patients were included. Acquired auricular
      deformities were mainly caused by bite injuries (22 %), traffic accidents (17 %),
      burns (9.5 %), and post-otoplasty complications (9.5 %). The upper third of the
      auricle was most often injured (41 %), followed by the entire auricle (19 %). 70
      % of cases required reconstruction with costal cartilage. The most common form of
      cutaneous cover was a postauricular skin flap (40 % of cases). This study gives a
      complete overview of causes and treatment of acquired auricular deformities. The
      results are comparable with the results of similar studies found in literature.
      Bite wounds are the leading cause of acquired auricular injuries. The upper third
      is most commonly affected. In the largest percentage of reconstructions, costal
      cartilage and a postauricular flap were used to correct the deformity.

PMID- 27714498
TI  - Effect of a liposomal hyaluronic acid gel loaded with dexamethasone in a guinea
      pig model after manual or motorized cochlear implantation.
AB  - Goals of cochlear implantation have shifted from complete insertion of the
      cochlear electrode array towards low traumatic insertion with minimally invasive
      techniques. The aim of this study was first to evaluate, in a guinea pig model of
      cochlear implantation, the effect of a motorized insertion technique on hearing
      preservation. The second goal was to study a new gel formulation containing
      dexamethasone phosphate loaded in liposomes (DEX-P). Guinea pigs had a unilateral
      cochlear implantation with either a manual technique (n = 12), or a motorized
      technique (n = 15), with a 0.4 mm diameter and 4 mm long array trough a
      cochleostomy. At the end of the procedure, hyaluronic acid gel containing drug
      free liposomes, or liposomes loaded with DEX-P, was injected into the bulla.
      Auditory brainstem responses thresholds were recorded before surgery and day 2
      and 7 after surgery. All the animals had increased auditory brainstem responses
      thresholds after the cochlear implantation. Implanted animals with the motorized
      insertion tool experienced a partial hearing recovery at day 7 but not in those
      implanted with the manual insertion procedure (p < 0.001). In the manually
      implanted animals, a partial recovery was observed when DEX-P contained in
      liposomal gel was locally administrated (p < 0.0001). Finally, no additive effect
      with the motorized insertion was noticed. The deleterious effect of manual
      insertion, during cochlear implantation, can be prevented with local DEX-P
      administration in the bulla at day 7. The use of a motorized tool performed more
      atraumatic electrode array insertion for postoperative hearing.

PMID- 27714499
TI  - Description of patients consulting the voice clinic regarding gender, age,
      occupational status, and diagnosis.
AB  - The purpose of this paper was to describe the gender, age, occupational status,
      and diagnosis of dysphonic patients. We retrospectively analyzed the medical
      records of 1079 patients examined at the Voice clinic of the University hospital
      of Liege in French-speaking Belgium. Overall, seven out of ten patients who
      attended the voice clinic for dysphonia were females. The patients' ages ranged
      from 4 to 93 (mean = 43.5). Females predominantly consulted at the age of 54 and
      males at the age of 9. Regarding the occupational status, workers represented
      more than half of our patients (53 %), while 11.2 % were unemployed, 15.4 % were
      students, and 19.9 % were retired. Regarding the diagnoses of the 1079 patients,
      nodules were the most common pathologies (n = 182, 16.9 % of the patients),
      prevailing in females (n = 142, 18.8 % of the females), and encountered in 16.8 %
      of the workers and 42.8 % of the students consulting the voice clinic. Following
      nodules, laryngeal mobility disorders were diagnosed in 16.4 % of the patients (n
      = 177), mainly females (n = 115), and was the most frequent diagnosis in retirees
      (n = 75, 34.9 %). The majority of the patients consulting the voice clinic for
      dysphonia were adult females, in their workforce, diagnosed with vocal nodules.
      The identification of the patients' characteristics and diagnoses is important to
      develop treatments and prevention of dysphonia, estimate their costs, and allow
      comparisons across referral centers.

PMID- 27714500
TI  - Astaxanthin supplementation attenuates immobilization-induced skeletal muscle
      fibrosis via suppression of oxidative stress.
AB  - Immobilization induces skeletal muscle fibrosis characterized by increasing
      collagen synthesis in the perimysium and endomysium. Transforming growth factor
      beta1 (TGF-beta1) is associated with this lesion via promoting differentiation of
      fibroblasts into myofibroblasts. In addition, reactive oxygen species (ROS) are
      shown to mediate TGF-beta1-induced fibrosis in tissues. These reports suggest the
      importance of ROS reduction for attenuating skeletal muscle fibrosis.
      Astaxanthin, a powerful antioxidant, has been shown to reduce ROS production in
      disused muscle. Therefore, we investigated the effects of astaxanthin
      supplementation on muscle fibrosis under immobilization. In the present study,
      immobilization increased the collagen fiber area, the expression levels of TGF
      beta1, alpha-smooth muscle actin, and superoxide dismutase-1 protein and ROS
      production. However, these changes induced by immobilization were attenuated by
      astaxanthin supplementation. These results indicate the effectiveness of
      astaxanthin supplementation on skeletal muscle fibrosis induced by ankle joint
      immobilization.

PMID- 27714501
TI  - IL28B rs12980275 and HLA rs4273729 genotypes as a powerful predictor factor for
      rapid, early, and sustained virologic response in patients with chronic hepatitis
      C.
AB  - Single-nucleotide polymorphisms (SNPs) in the Interleukin-28B (IL28B) gene and
      rs4273729 in the human leukocyte antigen (HLA) gene in chronic hepatitis C (CHC)
      virus infection are important for predicting treatment outcome. In this study,
      the distribution of IL28B SNPs (rs12979860 and rs12980275) and HLA rs4273729 in
      rapid virologic response (RVR), complete early virologic response (cEVR) and
      sustained virologic response (SVR) in HCV Iranian patients with CHC virus
      infection was assessed. IL28B genotyping and rs4273729 were performed using the
      amplification refractory mutation system (ARMS)-PCR and direct sequencing in 190
      CHC virus infections, respectively. RVR, cEVR, and SVR were 53.2 %, 78.9 %, and
      65.8 %, respectively. Multivariate regression analysis demonstrated that the
      responses significantly predicted SVR in patients with age <40 years (p = 0.008),
      HCV genotypes (p = 0.032), IL28B rs12979860 CC genotype (p < 0.001), rs12980275
      AA genotype (p < 0.001), rs4273729 GG genotype (p < 0.001), RVR (p < 0.001) and
      cEVR (p = 0.024). Three critical predictor factors based on RVR response were
      rs12979860 CC genotype (p = 0.033), rs12980275 AA genotype (p < 0.001) and
      rs4273729 GG genotype (p < 0.001), while rs12980275 AA (p = 0.003) and rs4273729
      GG genotypes (p < 0.001) predicted cEVR. For the first time in Iran, these
      results revealed that the rs12980275 and HLA rs4273729 are important for the
      treatment of CHC infection. These findings may help predict responses to CHC
      infection treatment and reduce the cost and side effects of therapy.

PMID- 27714502
TI  - Development of an updated PCR assay for detection of African swine fever virus.
AB  - Due to the current unavailability of vaccines or treatments for African swine
      fever (ASF), which is caused by African swine fever virus (ASFV), rapid and
      reliable detection of the virus is essential for timely implementation of
      emergency control measures and differentiation of ASF from other swine diseases
      with similar clinical presentations. Here, an improved PCR assay was developed
      and evaluated for sensitive and universal detection of ASFV. Primers specific for
      ASFV were designed based on the highly conserved region of the vp72 gene
      sequences of all ASFV strains available in GenBank, and the PCR assay was
      established and compared with two OIE-validated PCR tests. The analytic detection
      limit of the PCR assay was 60 DNA copies per reaction. No amplification signal
      was observed for several other porcine viruses. The novel PCR assay was more
      sensitive than two OIE-validated PCR assays when testing 14 strains of ASFV
      representing four genotypes (I, V, VIII and IX) from diverse geographical areas.
      A total of 62 clinical swine blood samples collected from Uganda were examined by
      the novel PCR, giving a high agreement (59/62) with a superior sensitive
      universal probe library-based real-time PCR. Eight out of 62 samples tested
      positive, and three samples with higher Ct values (39.15, 38.39 and 37.41) in the
      real-time PCR were negative for ASFV in the novel PCR. In contrast, one (with a
      Ct value of 29.75 by the real-time PCR) and two (with Ct values of 29.75 and
      33.12) ASFV-positive samples were not identified by the two OIE-validated PCR
      assays, respectively. Taken together, these data show that the novel PCR assay is
      specific, sensitive, and applicable for molecular diagnosis and surveillance of
      ASF.

PMID- 27714503
TI  - IL-1beta is a key cytokine that induces trypsin upregulation in the influenza
      virus-cytokine-trypsin cycle.
AB  - Severe influenza is characterized by a cytokine storm, and the influenza virus
      cytokine-trypsin cycle is one of the important mechanisms of viral multiplication
      and multiple organ failure. The aim of this study was to define the key
      cytokine(s) responsible for trypsin upregulation. Mice were infected with
      influenza virus strain A/Puerto Rico/8/34 (H1N1) or treated individually or with
      a combination of interleukin-1beta, interleukin-6, and tumor necrosis factor
      alpha. The levels of these cytokines and trypsin in the lungs were monitored. The
      neutralizing effects of anti-IL-1beta antibodies on cytokine and trypsin
      expression in human A549 cells and lung inflammation in the infected mice were
      examined. Infection induced interleukin-1beta, interleukin-6, tumor necrosis
      factor alpha, and ectopic trypsin in mouse lungs in a dose- and time-dependent
      manner. Intraperitoneal administration of interleukin-1beta combined with other
      cytokines tended to upregulate trypsin and cytokine expression in the lungs, but
      the combination without interleukin-1beta did not induce trypsin. In contrast,
      incubation of A549 cells with interleukin-1beta alone induced both cytokines and
      trypsin, and anti-interleukin-1beta antibody treatment abrogated these effects.
      Administration of the antibody in the infected mice reduced lung inflammation
      area. These findings suggest that IL-1beta plays a key role in trypsin
      upregulation and has a pathological role in multiple organ failure.

PMID- 27714504
TI  - Diabetic charcot neuroarthropathy: prevalence, demographics and outcome in a
      regional referral centre.
AB  - BACKGROUND: Diabetic Charcot neuroarthropathy (DCN) is a devastating complication
      for people with diabetes mellitus. The failure to diagnose DCN and institute
      treatment in the acute phase leads to permanent deformity and significant
      morbidity. There is a paucity of data on the prevalence and characteristics of
      patients who have developed this complication of diabetes. AIMS: To determine the
      prevalence, clinical characteristics and outcomes of patients with DCN from 2006
      to 2012. METHODS: Case finding was performed by searching three independent lists
      for the period 2006-2012 including: SYNGO radiology database, HIPE database of
      hospital discharges, and, combined list from podiatry, endocrinology, vascular
      surgery and orthopaedic clinics. A consensus meeting with chart review was
      undertaken to confirm diagnosis of DCN. A proforma was completed from chart
      review to determine clinical characteristics, initial treatment and outcomes for
      patients with DCN. RESULTS: Forty cases of DCN were identified, resulting in an
      estimated period prevalence of 0.3 %. The majority of patients were male (68 %);
      most patients had T2DM (73 %). Mean +/- SD for age was 58 +/- 10 years and mean
      duration of diabetes was 15 +/- 9 years. In the acute phase of DCN, offloading
      was performed in 50 %. Bisphosphonates were administered to 5 % and surgery
      undertaken in 5 % of cases. 38 % of patients developed subsequent foot ulceration
      and 20 % required amputation. CONCLUSIONS: This is the first prevalence estimate
      of DCN in Ireland. These data suggest diagnosis of DCN is missed in the acute
      phase. There exists a significant risk of diabetic foot ulceration and amputation
      with DCN.

PMID- 27714505
TI  - Grapevine phenology and climate change in Georgia.
AB  - While the climate of Western Europe has been deeply affected by the abrupt
      climate change that took place in the late '1980s of the twentieth century, a
      similar signal is detected only few years later, in 1994, in Georgia. Grapevine
      phenology is deeply influenced by climate and this paper aimed to analyze how
      phenological timing changed before and after the climatic change of 1994.
      Availability of thermal resources in the two climatic phases for the five
      altitudinal belts in the 0-1250-m range was analyzed. A phenological dataset
      gathered in two experimental sites during the period 2012-2014, and a suitable
      thermal dataset was used to calibrate a phenological model based on the normal
      approach and able to describe BBCH phenological stages 61 (beginning of
      flowering), 71 (fruit set), and 81 (veraison). Calibration was performed for four
      relevant Georgian varieties (Mtsvane Kakhuri, Rkatsiteli, Ojaleshi, and
      Saperavi). The model validation was performed on an independent 3-year dataset
      gathered in Gorizia (Italy). Furthermore, in the case of variety Rkatsiteli, the
      model was applied to the 1974-2013 thermal time series in order to obtain
      phenological maps of the Georgian territory. Results show that after the climate
      change of 1994, Rkatsiteli showed an advance, more relevant at higher altitudes
      where the whole increase of thermal resource was effectively translated in
      phenological advance. For instance the average advance of veraison was 5.9 days
      for 250-500 m asl belt and 18.1 days for 750-1000 m asl). On the other hand, at
      lower altitudes, phenological advance was depleted by superoptimal temperatures.
      As a final result, some suggestions for the adaptation of viticultural practices
      to the current climatic phase are provided.

PMID- 27714506
TI  - Balneological outpatient treatment for patients with knee osteoarthritis; an
      effective non-drug therapy option in daily routine?
AB  - This study aims to compare the effects of balneological treatments applied at
      consecutive and intermittent sessions without interfering with their daily
      routine in patients with knee osteoarthritis. This is a randomized, controlled,
      single-blind clinical trial. Fifty patients diagnosed with knee osteoarthritis
      were included. The patients were divided into two groups. All patients were given
      a total of ten sessions of balneological treatment consisting of hydrotherapy and
      mud pack therapy. Group 1 received consecutive treatment for 2 weeks, while group
      2 received intermittent treatment for 5 weeks. Local peloid packs at 45  degrees
      C were applied for 20 min, after a tap water (38  degrees C) bath. Evaluations
      were conducted before, after treatment, and at 12th week of post-treatment by
      Pain (VAS), Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC), and Short Form-36 (SF-36). Both balneological treatment regimens of knee
      osteoarthritis had statistically significant clinical effects as well as effects
      on the quality of life. Patients' well-being continued at 3 months, except for
      joint stiffness (WOMAC), role-emotional (SF-36), and vitality (SF-36) in group 1
      and for mental health (SF-36) in both groups. Both patient groups had improved
      compared to baseline. However, at 3 months after the treatment, the well-being of
      group 2 was unable to be maintained in terms of role-physical (SF-36) parameter,
      while the well-being of group 1 was unable to be maintained in terms of pain,
      WOMAC (pain, physical functions, total), and SF-36 (physical functioning, role
      physical, pain, role-emotional, and mental health) variables, compared to data
      obtained immediately after treatment. Our study suggests that traditional and
      intermittent balneological therapies have similar efficacy in patients with knee
      osteoarthritis.

PMID- 27714507
TI  - NMR assignments of the GacS histidine-kinase periplasmic detection domain from
      Pseudomonas aeruginosa PAO1.
AB  - Pseudomonas aeruginosa is a highly adaptable opportunistic pathogen. It can
      infect vulnerable patients such as those with cystic fibrosis or hospitalized in
      intensive care units where it is responsible for both acute and chronic
      infection. The switch between these infections is controlled by a complex
      regulatory system involving the central GacS/GacA two-component system that
      activates the production of two small non-coding RNAs. GacS is a histidine kinase
      harboring one periplasmic detection domain, two inner-membrane helices and three
      H1/D1/H2 cytoplasmic domains. By detecting a yet unknown signal, the GacS
      histidine-kinase periplasmic detection domain (GacSp) is predicted to play a key
      role in activating the GacS/GacA pathway. Here, we present the chemical shift
      assignment of 96 % of backbone atoms (HN, N, C, Calpha, Cbeta and Halpha), 88 %
      aliphatic hydrogen atoms and 90 % of aliphatic carbon atoms of this domain. The
      NMR-chemical shift data, on the basis of Talos server secondary structure
      predictions, reveal that GacSp consists of 3 beta-strands, 3 alpha-helices and a
      major loop devoid of secondary structures.

PMID- 27714508
TI  - Erratum to: Severe Acute Hepatocellular Injury Attributed to OxyELITE Pro: A Case
      Series.

PMID- 27714509
TI  - Adverse Effects of Domperidone: Prolonged QuesT for Knowledge?

PMID- 27714511
TI  - Interventional EUS Using a Flexible 19-Gauge Needle: An International Multicenter
      Experience in 162 Patients.
AB  - BACKGROUND AND AIMS: To facilitate access for interventional EUS, flexible
      (nitinol) 19-G needles have been introduced to permit needle puncture even when
      the echoendoscope is in an angulated position, such as in the second part of the
      duodenum. The aims of the study were to evaluate the performance of a flexible 19
      G needle during interventional EUS procedures and compare outcomes when the
      echoendoscope was in the straight versus angulated position. METHODS: A
      retrospective review was undertaken of 162 consecutive patients that underwent a
      variety of interventional EUS procedures with a flexible 19-G needle across five
      centers. Patients were subdivided into categories (straight or angulated)
      depending on the echoendoscope position used for obtaining access to the area of
      interest (Fig. 1). Fig. 1 Flexible 19-G needle design. a The needle is able to
      exit the sheath despite the rotated position. b The needle beveled needle tip
      RESULTS: In the entire cohort, needle-specific technical success was achieved in
      93.2 %, procedural success in 85.2 %, and overall clinical success in 76.5 % of
      cases at a mean follow-up of 3.1 months. Needle-specific technical success was
      similar between the straight and angulated cohorts (94.0 vs. 91.2 %, p = 0.74).
      Procedural success (86.7 vs. 77.2 %, p = 0.05), and rate of clinical success was
      similar between the cohorts (83.3 vs. 86.4 %, p = 0.79), respectively. Overall
      adverse events were noted in 14.2 % of patients with no difference between the
      straight and angulated cohorts (p = 0.48). CONCLUSIONS: This study demonstrates
      equivalent technical success, clinical success and safety of using a flexible 19
      G needle in straight and angulated endoscope positions for interventional EUS.
      Therefore, a flexible needle may be considered where an angulated echoendoscope
      position is encountered.

PMID- 27714512
TI  - Optic disc tilt direction affects regional visual field progression rates in
      myopic eyes with open-angle glaucoma.
AB  - PURPOSE: To compare global and regional visual field (VF) progression rates and
      determine clinical factors associated with rapid VF progression in myopic
      patients with open-angle glaucoma (OAG) with different disc tilt directions.
      METHODS: The medical records of 182 eyes from 182 myopic OAG patients with
      progressive VF deterioration during follow-up were analyzed. The rates of change
      in the mean thresholds of the global and regional VF areas of the horizontal and
      vertical disc tilt (HDT and VDT) groups were compared using a linear mixed model
      after controlling for confounding covariates. Clinical factors associated with
      rapid VF progression in global and regional VF areas were investigated. RESULTS:
      The VDT group showed significantly faster VF progression at inferior regional
      zones than the HDT group (P < 0.05). Based on a multivariate linear mixed model,
      VDT was associated with faster bi-hemifield VF progression in the GHT map,
      whereas HDT was associated with faster single-hemifield VF progression.
      CONCLUSIONS: Myopic OAG eyes show significantly different regional VF progression
      rates according to disc tilt direction. VDT is an independent predictor of a
      rapid rate of regional VF progression in both hemifields, whereas HDT predicts
      rapid regional VF progression in a single hemifield.

PMID- 27714510
TI  - Cardiovascular Risk Reduction in Patients with Nonalcoholic Fatty Liver Disease:
      The Potential Role of Ezetimibe.
AB  - Nonalcoholic fatty liver disease (NAFLD) is widely considered to be the hepatic
      manifestation of the metabolic syndrome and is closely linked to dyslipidemia,
      obesity, and insulin resistance. Patients with NAFLD have increased mortality
      when compared to the general population, primarily related to cardiovascular
      disease or malignancy. The biologic mechanisms that link NAFLD to cardiovascular
      disease include expansion of visceral adipose tissue, atherogenic dyslipidemia,
      impaired insulin signaling, systemic inflammation, and endothelial dysfunction.
      Currently, there are no approved therapies for NAFLD. It has recently been
      hypothesized that reducing the delivery of dietary cholesterol using the
      hypolipidemic agent, ezetimibe, could benefit patients with NAFLD. By potently
      inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) sterol receptor on intestinal
      enterocytes and within the liver, ezetimibe blocks exogenous cholesterol
      absorption and has been shown to improve biochemical markers of NAFLD, improve
      insulin sensitivity and decrease hepatic steatosis. This review summarizes the
      clinical and epidemiological evidence for the relationship between NAFLD and
      cardiovascular risk and examines the potential therapeutic role of ezetimibe.

PMID- 27714513
TI  - Comparison of two individualized treatment regimens with ranibizumab for diabetic
      macular edema.
AB  - PURPOSE: To compare outcomes between an as-needed and a treat-and-extend regimen
      in managing diabetic macular edema with intravitreal ranibizumab. METHODS: This
      was a retrospective, single-centre, comparative case series on 46 treatment naive
      patients with diabetic macular edema. Twenty-two patients were treated following
      an optical coherence tomography guided treat-and-extend protocol (OCTER), and 24
      patients were treated according to a visual acuity guided pro re nata regimen
      (VAPRN) at a tertiarry referral centre. The main outcome measures were best
      corrected visual acuity, central retinal thickness, and the number of ranibizumab
      injections, as well as visits after 12 months of treatment. RESULTS: After 12
      months, the mean gain in best-corrected visual acuity (+/- standard deviation)
      was 8.3 +/- 6.7 versus 9.3 +/- 8.9 letters in the VAPRN and OCTER group,
      respectively (p = 0.3). The mean decrease in central retinal thickness was 68.1
      +/- 88.0 MUm in the VAPRN group and 117.6 +/- 114.4 MUm in the OCTER group (p =
      0.2). The mean number of ranibizumab injections was significantly different
      between the VAPRN (5.9 +/- 1.8) and the OCTER protocol (8.9 +/- 2.0) (p < 0.001).
      CONCLUSION: The visual acuity driven retreatment regimen resulted in a similar
      visual acuity outcome like optical coherence tomography guided retreatment for
      diabetic macular edema. Although the number of visits was similar in both groups,
      patients in the VAPRN group received significantly fewer intravitreal injections
      than patients in the OCTER group.

PMID- 27714514
TI  - Hippocampal GluA2 and GluA4 protein but not corresponding mRNA and promoter
      methylation levels are modulated at retrieval in spatial learning of the rat.
AB  - AMPA receptors mediate most fast excitatory synaptic transmission in the brain.
      Highly dynamic AMPA receptors are subjected to trafficking, recycling, and/or
      degradation and replacement. Changes in AMPA receptor abundance is an important
      mechanism involved in learning and memory formation. Results obtained with the
      Morris water maze (MWM), a paradigm for testing spatial memory in rodent,
      correlate with hippocampal synaptic plasticity and NMDA function. Different
      phases of spatial learning like acquisition and retrieval involve AMPA receptors.
      Long-term memory formation requires dynamic changes in gene transcription and
      protein synthesis. It is, however, not known so far if epigenetic marks such as
      DNA methylation and mRNA levels participate in regulation of AMPA receptors in
      hippocampus during memory retrieval. In the present study, rats were trained or
      untrained in the MWM. Steady state levels of hippocampal GluA1-4 mRNA were
      determined by RT-PCR and promoter methylation levels of GluA1-4 by in-house
      developed bisulfite pyrosequencing methods. GluA1-4 protein levels were
      determined in parallel in a membrane fraction by SDS-PAGE followed by Western
      blotting. Our results indicate that changes of hippocampal membrane AMPA
      receptors were modulated at the protein level, while no changes were observed at
      the mRNA and at the promoter methylation level of hippocampal GluA1-4. Training
      in the MWM at retrieval may, therefore, involve GluA2 and GluA4 subunits that may
      be regulated by protein stability or trafficking as protein determinations were
      carried out in a hippocampal membrane fraction.

PMID- 27714516
TI  - Role of amino acid residues surrounding the phosphorylation site in peptide
      substrates of G protein-coupled receptor kinase 2 (GRK2).
AB  - A series of amino acid substitutions was made in a previously identified beta
      tubulin-derived GRK2 substrate peptide (404DEMEFTEAESNMN416) to examine the role
      of amino acid residues surrounding the phosphorylation site. Anionic amino acid
      residues surrounding the phosphorylation site played an important role in the
      affinity for GRK2. Compared to the original peptide, a modified peptide (Ac
      EEMEFSEAEANMN-NH2) exhibited markedly higher affinity for GRK2, but very low
      affinity for GRK5, suggesting that it can be a sensitive and selective peptide
      for GRK2.

PMID- 27714515
TI  - Human splanchnic amino-acid metabolism.
AB  - Plasma levels of several amino acids are correlated with metabolic dysregulation
      in obesity and type 2 diabetes. To increase our understanding of human amino-acid
      metabolism, we aimed to determine splanchnic interorgan amino-acid handling.
      Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy
      were included in this study. Blood was sampled from the portal vein, hepatic
      vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal
      vein, and the radial artery during surgery. The difference between arterial and
      venous concentrations of 21 amino acids was determined using liquid
      chromatography as a measure of amino-acid metabolism across a given organ.
      Whereas glutamine was significantly taken up by the small intestine (121.0 +/-
      23.8 umol/L; P < 0.0001), citrulline was released (-36.1 +/- 4.6 umol/L; P <
      0.0001). This, however, was not seen for the colon. Interestingly, the liver
      showed a small, but a significant uptake of citrulline from the circulation (4.8
      +/- 1.6 umol/L; P = 0.0138) next to many other amino acids. The kidneys showed a
      marked release of serine and alanine into the circulation (-58.0 +/- 4.4 umol/L
      and -61.8 +/- 5.2 umol/L, P < 0.0001), and a smaller, but statistically
      significant release of tyrosine (-12.0 +/- 1.3 umol/L, P < 0.0001). The spleen
      only released taurine (-9.6 +/- 3.3 umol/L; P = 0.0078). Simultaneous blood
      sampling in different veins provides unique qualitative and quantitative
      information on integrative amino-acid physiology, and reveals that the well-known
      intestinal glutamine-citrulline pathway appears to be functional in the small
      intestine but not in the colon.

PMID- 27714517
TI  - Learning curve in robotic rectal cancer surgery: current state of affairs.
AB  - INTRODUCTION: Robotic-assisted rectal cancer surgery offers multiple advantages
      for surgeons, and it seems to yield the same clinical outcomes as regards the
      short-time follow-up of patients compared to conventional laparoscopy. This
      surgical approach emerges as a technique aiming at overcoming the limitations
      posed by rectal cancer and other surgical fields of difficult access, in order to
      obtain better outcomes and a shorter learning curve. MATERIAL AND METHODS: A
      systematic review of the literature of robot-assisted rectal surgery was carried
      out according to the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) statement. The search was conducted in October 2015 in PubMed,
      MEDLINE and the Cochrane Central Register of Controlled Trials, for articles
      published in the last 10 years and pertaining the learning curve of robotic
      surgery for colorectal cancer. It consisted of the following key words: "rectal
      cancer/learning curve/robotic-assisted laparoscopic surgery". RESULTS: A total of
      34 references were identified, but only 9 full texts specifically addressed the
      analysis of the learning curve in robot-assisted rectal cancer surgery, 7 were
      case series and 2 were non-randomised case-comparison series. Eight papers used
      the cumulative sum (CUSUM) method, and only one author divided the series into
      two groups to compare both. The mean number of cases for phase I of the learning
      curve was calculated to be 29.7 patients; phase II corresponds to a mean number
      37.4 patients. The mean number of cases required for the surgeon to be classed as
      an expert in robotic surgery was calculated to be 39 patients. CONCLUSION:
      Robotic advantages could have an impact on learning curve for rectal cancer and
      lower the number of cases that are necessary for rectal resections.

PMID- 27714518
TI  - Laparoscopic complete mesocolic excision for right-sided colon cancer using a
      cranial approach: anatomical and embryological consideration.
AB  - BACKGROUND: Complete mesocolic excision (CME) with central vascular ligation
      (CVL) should be employed for the treatment of colon cancer patients because of
      its superior oncological outcomes. However, this technique is technically
      challenging in laparoscopic right hemicolectomy because of the anatomical
      complexity of the transverse mesocolon. METHODS: We focused on the embryology and
      anatomy of the transverse mesocolon to overcome the difficulty of this surgery.
      The validity and efficacy of a cranial approach in achieving CME with CVL in
      laparoscopic right hemicolectomy was elucidated from the embryological point of
      view. RESULTS: In total, 28 consecutive patients with right-sided colon cancer
      were treated by laparoscopic right hemicolectomy using a cranial approach. There
      were no conversion to open surgery or switching to another approach. Using this
      approach, torsion and fusion of the transverse mesocolon, which occurred during
      embryological development, could be reversed and the complex anatomy of the
      transverse mesocolon could be simplified before performing CVL of colonic
      vessels. CONCLUSIONS: A cranial approach is considered valid and useful for CME
      with CVL in laparoscopic right hemicolectomy from the embryological point of
      view.

PMID- 27714519
TI  - Laparoscopic lavage in perforated purulent diverticulitis-is it time for
      definitive conclusions?

PMID- 27714520
TI  - The use of transureteroureterostomy during ureteral reconstruction for advanced
      primary or recurrent pelvic malignancy in the era of multimodal therapy.
AB  - PURPOSE: Cancerous involvement of a ureter is sometimes encountered in pelvic
      surgery for malignancy. We usually perform transureteroureterostomy (TUU) in
      cases of unilateral lower ureteral cancerous involvement. We report the outcomes
      in patients treated with TUU in our institute. METHODS: We retrospectively
      reviewed the medical records of 11 patients who underwent TUU between June 2006
      and September 2015. RESULTS: The primary disease was colon cancer in five
      patients, rectal cancer in four, and uterine cervical cancer and ovarian cancer
      in one patient each. Early postoperative complications relevant to TUU occurred
      in four patients; however, three patients were managed conservatively and
      recovered quickly. Only one patient developed ureteral obstruction, which
      resulted from anastomotic hematoma. Follow-up periods ranged from 5 to 78 months
      with a median of 28 months. The median estimated glomerular filtration rate
      before and after TUU was 59 ml/min (range, 31-90 ml/min) and 62.0 ml/min (range,
      43-127 mL/min), respectively. No patients experienced worsening of their renal
      function or recurrent urinary tract infection. CONCLUSIONS: Short-term outcomes
      are good and long-term renal function is maintained following TUU. TUU is
      considered a feasible technique for ureteral reconstruction for pelvic
      malignancy, and TUU has great potential in the era of multimodal therapy.

PMID- 27714521
TI  - Prospective multicenter registration study of colorectal cancer: significant
      variations in radicality and oncosurgical quality-Swiss Group for Clinical Cancer
      Research Protocol SAKK 40/00.
AB  - PURPOSE: This study aimed to investigate in a multicenter cohort study the
      radicality of colorectal cancer resections, to assess the oncosurgical quality of
      colorectal specimens, and to compare the performance between centers. METHODS:
      One German and nine Swiss hospitals agreed to prospectively register all patients
      with primary colorectal cancer resected between September 2001 and June 2005. The
      median number of eligible patients with one primary tumor included per center was
      95 (range 12-204). RESULTS: The following variations of median values or
      percentages between centers were found: length of bowel specimen 20-39 cm (25.8
      cm), maximum height of mesocolon 6.5-12.5 cm (9.0 cm), number of examined lymph
      nodes 9-24 (16), distance to nearer bowel resection margin in colon cancer 4.8-12
      cm (7 cm), and in rectal cancer 2-3 cm (2.5 cm), central ligation of major artery
      40-97 % (71 %), blood loss 200-500 ml (300 ml), need for perioperative blood
      transfusion 5-40 % (19 %), tumor opened during mobilization 0-11 % (5 %), T4
      tumors not en-bloc resected 0-33 % (4 %), inadvertent perforation of
      mesocolon/mesorectum 0-8 % (4 %), no-touch isolation technique 36-86 % (67 %),
      abdominoperineal resection for rectal cancer 0-30 % (17 %), rectal cancer
      specimen with circumferential margin <=1 mm 0-19 % (10 %), in-hospital mortality
      0-6 % (2 %), anastomotic leak or intra-abdominal abscess 0-17 % (7 %), re
      operation 0-17 % (8 %). CONCLUSION: In colorectal cancer, surgery considerable
      variations between different centers were found with regard to radicality and
      oncosurgical quality, suggesting a potential for targeted improvement of surgical
      technique.

PMID- 27714522
TI  - Factors Associated with Health Information Seeking, Processing, and Use Among HIV
      Positive Adults in the Dominican Republic.
AB  - Effective treatment and management of human immunodeficiency virus (HIV) depend
      on patients' ability to locate, comprehend, and apply health information. This
      study's purpose was to identify characteristics associated with these skills
      among HIV positive adults in the Dominican Republic. An information behavior
      survey was administered to 107 participants then three logistic regressions were
      conducted to identify characteristics associated with information seeking,
      processing, and use. Never having cared for someone who was sick was
      significantly associated with less information seeking, processing, and use.
      Males were more likely to be active information seekers and those who had
      attended the clinic for six or fewer years were less likely to actively seek
      information. Younger individuals had increased odds of higher information
      processing and those without comorbidities had increased odds of more information
      use. Results may inform researchers, organizations, and providers about how
      patients interact with health information in limited resource settings.

PMID- 27714524
TI  - Evolution of Monitoring and Evaluation of AIDS Response in Ukraine: Laying the
      Groundwork for Evidence-Based Health Care.
AB  - Once facing the most severe HIV epidemic in Eastern Europe, Ukraine has built an
      elaborate Monitoring and Evaluation (M&E) system to track the response to AIDS.
      This system was developed using recommendations and input from multiple
      international expert organizations and donors and, at the current stage, serves
      as a best practice model in many areas. The present paper aims to provide a
      comprehensive overview of the evolution of the M&E system in Ukraine since its
      inception. Notable achievements and challenges are described and illustrated by
      epidemiological data and the recommendations for future development are
      discussed. Unique experiences and advances in M&E in Ukraine may be useful to
      other countries facing similar epidemiological, structural or methodological
      issues.

PMID- 27714523
TI  - Two-Year Trajectories of Sexual Risk Behaviors Among Drug-Using Adolescents and
      Emerging Adults in an Urban Community.
AB  - Among 14-24 year-olds who used drugs and were recruited from an emergency
      department, we examined 2-year trajectories of sexual risk behaviors. We
      hypothesized that those in higher risk trajectories would have more severe
      substance use, mental health concerns, and dating violence involvement at
      baseline. Analyses identified three behavioral trajectories. Individuals in the
      highest risk trajectory had a more severe profile of baseline alcohol use,
      marijuana use, dating violence involvement, and mental health problems. Future
      research will examine longitudinal differences in risk factors across
      trajectories. Understanding risk factors for sexual risk behavior trajectories
      can inform the delivery and tailoring of prevention interventions.

PMID- 27714525
TI  - A Comparison of Adherence Timeframes Using Missed Dose Items and Their
      Associations with Viral Load in Routine Clinical Care: Is Longer Better?
AB  - Questions remain regarding optimal timeframes for asking about adherence in
      clinical care. We compared 4-, 7-, 14-, 30-, and 60-day timeframe missed dose
      items with viral load levels among 1099 patients on antiretroviral therapy in
      routine care. We conducted logistic and linear regression analyses examining
      associations between different timeframes and viral load using Bayesian model
      averaging (BMA). We conducted sensitivity analyses with subgroups at increased
      risk for suboptimal adherence (e.g. patients with depression, substance use). The
      14-day timeframe had the largest mean difference in adherence levels among those
      with detectable and undetectable viral loads. BMA estimates suggested the 14-day
      timeframe was strongest overall and for most subgroups although findings differed
      somewhat for hazardous alcohol users and those with current depression. Adherence
      measured by all missed dose timeframes correlated with viral load. Adherence
      calculated from intermediate timeframes (e.g. 14-day) appeared best able to
      capture adherence behavior as measured by viral load.

PMID- 27714526
TI  - The Effectiveness and Safety of Sleeve Gastrectomy in the Obese Elderly Patients:
      a Systematic Review and Meta-Analysis.
AB  - BACKGROUND: This systematic review was performed to compare the effectiveness and
      safety of SG in the obese elderly patients with the young ones. METHODS: Cohort
      studies that compared outcomes among old and young patients who had undergone SG
      were included. Summary odds ratios were estimated using a random effect model.
      RESULTS: Eleven studies were included. Old patients had a worse outcome in
      percentage of excess weight loss than the young ones (SMD -0.39, 95 % CI -0.55 to
      -0.24). No significant differences were recorded in resolution of co-morbidities:
      type 2 diabetes mellitus (OR 1.60, 95 % CI 0.84-3.05), hypertension (OR 1.05, 95
      % CI 0.65-1.68), dyslipidemia (OR 1.38, 95 % CI 0.68-2.80), OSAS (OR 0.64, 95 %
      CI 0.30-1.34), or postoperative complications (OR 0.89, 95 % CI 0.51-1.55)
      between the elderly and the young who had undergone SG. CONCLUSIONS: SG was
      effective for weight loss and resolution of co-morbidities with low complication
      rate in the obese elderly patients.

PMID- 27714527
TI  - Banded Gastric Bypass: Better Long-Term Results? A Cohort Study with Minimum 5
      Year Follow-Up.
AB  - BACKGROUND: While gastric bypass has been the treatment of choice for morbid
      obesity, insufficient weight loss and even weight regain has been observed in a
      sub-group of patients. Dilatation of the pouch, pouch outlet, and proximal
      alimentary limb have been suggested to cause weight regain on the long term. The
      banded gastric bypass surgery has been introduced to overcome this problem.
      METHODS: Four hundred thirty-two patients (n = 254, non-banded/n = 178, banded
      GaBP RingTM) were followed-up for 5 years. Patients were evaluated for weight
      loss, % excess weight loss (%EWL), weight regain and BMI. RESULTS: No significant
      differences between groups in the first year following surgery were observed in
      terms of weight loss and %EWL. %EWL at 5 years was as follows: non-banded 65.2 +/
      20.0 %; banded 74.0 +/- 15.1 %. At 5 years, the banded group showed more weight
      loss (non-banded 35.4 +/- 12.5; banded 43.9 +/- 11.9 kg, P < 0.0001); weight
      regain was significantly higher in the non-banded group (P < 0.0001). Only minor
      complications were reported; no signs of ring migration or slippage were
      reported. CONCLUSION: Although, following the first year after surgery, no
      differences in treatment groups were observed in terms of weight loss, 5 years
      following surgery, patients who received banded surgery maintained better weight
      loss and had less weight regain compared to the non-banded group. These results
      suggest that laparoscopic banded gastric bypass using a silastic ring was
      effective in maintaining weight loss on the long term, while the complication
      rate was low. The banded gastric bypass is regarded by us as the new gold
      standard.

PMID- 27714528
TI  - Adhesion of multimode adhesives to enamel and dentin after one year of water
      storage.
AB  - OBJECTIVES: This study aimed to evaluate the ultramorphological characteristics
      of tooth-resin interfaces and the bond strength (BS) of multimode adhesive
      systems to enamel and dentin. METHODS: Multimode adhesives (Scotchbond Universal
      (SBU) and All-Bond Universal) were tested in both self-etch and etch-and-rinse
      modes and compared to control groups (Optibond FL and Clearfil SE Bond (CSB)).
      Adhesives were applied to human molars and composite blocks were incrementally
      built up. Teeth were sectioned to obtain specimens for microtensile BS and TEM
      analysis. Specimens were tested after storage for either 24 h or 1 year. SEM
      analyses were performed to classify the failure pattern of beam specimens after
      BS testing. RESULTS: Etching increased the enamel BS of multimode adhesives;
      however, BS decreased after storage for 1 year. No significant differences in
      dentin BS were noted between multimode and control in either evaluation period.
      Storage for 1 year only reduced the dentin BS for SBU in self-etch mode. TEM
      analysis identified hybridization and interaction zones in dentin and enamel for
      all adhesives. Silver impregnation was detected on dentin-resin interfaces after
      storage of specimens for 1 year only with the SBU and CSB. CONCLUSIONS: Storage
      for 1 year reduced enamel BS when adhesives are applied on etched surface;
      however, BS of multimode adhesives did not differ from those of the control
      group. In dentin, no significant difference was noted between the multimode and
      control group adhesives, regardless of etching mode. CLINICAL RELEVANCE: In
      general, multimode adhesives showed similar behavior when compared to traditional
      adhesive techniques. Multimode adhesives are one-step self-etching adhesives that
      can also be used after enamel/dentin phosphoric acid etching, but each product
      may work better in specific conditions.

PMID- 27714529
TI  - Interhemispheric resting-state functional connectivity of the claustrum in the
      awake and anesthetized states.
AB  - The claustrum is a brain region whose function remains unknown, though many
      investigators suggest it plays a role in conscious attention. Resting-state
      functional magnetic resonance imaging (RS-fMRI) has revealed how anesthesia
      alters many functional connections in the brain, but the functional role of the
      claustrum with respect to the awake versus anesthetized states remains unknown.
      Therefore, we employed a combination of seed-based RS-fMRI and neuroanatomical
      tracing to reveal how the anatomical connections of the claustrum are related to
      its functional connectivity during quiet wakefulness and the isoflurane-induced
      anesthetic state. In awake rats, RS-fMRI indicates that the claustrum has
      interhemispheric functional connections with the mediodorsal thalamus (MD) and
      medial prefrontal cortex (mPFC), as well as other known connections with cortical
      areas that correspond to the connections revealed by neuroanatomical tracing.
      During deep isoflurane anesthesia, the functional connections of the claustrum
      with mPFC and MD were significantly attenuated, while those with the rest of
      cortex were not significantly altered. These changes in claustral functional
      connectivity were also observed when seeds were placed in mPFC or MD during RS
      fMRI comparisons of the awake and deeply anesthetized states. Collectively, these
      data indicate that the claustrum has functional connections with mPFC and MD
      thalamus that are significantly lessened by anesthesia.

PMID- 27714530
TI  - Efficacy of ginger for prophylaxis of chemotherapy-induced nausea and vomiting in
      breast cancer patients receiving adriamycin-cyclophosphamide regimen: a
      randomized, double-blind, placebo-controlled, crossover study.
AB  - PURPOSE: The purpose of this study is to determine the efficacy of ginger for
      reducing chemotherapy-induced nausea and vomiting (CINV) in breast cancer
      patients receiving adriamycin and cyclophosphamide (AC) regimens. METHODS: We
      enrolled breast cancer patients receiving AC who experienced moderate to severe
      nausea or vomiting during the first chemotherapy cycle. Subjects were randomized
      to receive a 500-mg ginger capsule or placebo twice a day for 5 days starting on
      the first day of the second AC cycle and were switched to the other treatment in
      the third cycle. All participants also received ondansetron and dexamethasone for
      CINV prophylaxis. Nausea severity was recorded once a day during the first 5 days
      of each cycle. The primary outcome was reduction in nausea score. RESULTS: Thirty
      four subjects (68 cycles of AC) were enrolled. Mean (range) maximum nausea score
      in the first AC cycle was 58 (40-90). Thirty-three subjects (97 %) received the
      same AC doses in the second as in the third cycle. Mean (+/-standard error)
      maximum nausea scores in patients receiving ginger and placebo were 35.36 (+/
      4.43) and 32.17 (+/-3.71), respectively. The difference in mean maximum nausea
      scores was 3 (95 % confidence interval, -3 to 9; P = 0.3). There were no
      significant differences between ginger and placebo in terms of vomiting incidence
      and severity, rescue medication use, chemotherapy compliance, and adverse events.
      CONCLUSIONS: Ginger (500 mg) twice daily was safe, but conferred no additional
      benefit in terms of reducing nausea severity in breast cancer patients receiving
      AC and ondansetron and dexamethasone for CINV prophylaxis.

PMID- 27714531
TI  - Unequal cancer survivorship care: addressing cultural and sociodemographic
      disparities in the clinic.
AB  - The number of individuals diagnosed with cancer is growing worldwide. Cancer
      patients from underserved populations have widely documented disparities through
      the continuum of cancer care. As the number of cancer survivors (i.e.,
      individuals who have completed cancer treatment) from underserved populations
      also continue to grow, these individuals may continue to experience barriers to
      survivorship care, resulting in persistent long-term negative impacts on health
      and quality of life. In addition, there is limited participation of survivors
      from underserved populations in clinical trials and other research studies. To
      address disparities and change practices in survivorship care, a better
      understanding of the roles of both socioeconomic status (SES) and of culture in
      cancer care disparities and the relevance of these to providing high-quality care
      is needed. SES and culture often overlap but are not identical; understanding the
      impact of each is especially relevant to survivorship care. To enhance health
      equity among cancer survivors, clinicians need to practice culturally competent
      care, address cultural beliefs and practices that may influence survivors'
      beliefs and activities, gain awareness of historical patterns of medical care in
      the survivor's community, and consider how barriers to cross-cultural
      communications may hinder communication in clinical settings. While the design
      and implementation of survivorship care programs emphasizing effectiveness and
      equity is complex and potentially time consuming, it is critical for providing
      optimal care for all survivors, including those from the most vulnerable
      populations.

PMID- 27714532
TI  - Determining best methods to screen for religious/spiritual distress.
AB  - PURPOSE: This study sought to validate for the first time a brief screening
      measure for religious/spiritual (R/S) distress given the Commission on Cancer's
      mandated screening for psychosocial distress including spiritual distress.
      METHODS: Data were collected in conjunction with an annual survey of adult
      hematopoietic cell transplantation (HCT) survivors. Six R/S distress screeners
      were compared to the Brief RCOPE, Negative Religious Coping subscale as the
      reference standard. We pre-specified validity as a sensitivity score of at least
      85 %. As no individual measure attained this, two post hoc analyses were
      conducted: analysis of participants within 2 years of transplantation and of a
      simultaneous pairing of items. Data were analyzed from 1449 respondents whose
      time since HCT was 6 months to 40 years. RESULTS: For the various single-item
      screening protocols, sensitivity ranged from 27 (spiritual/religious concerns) to
      60 % (meaning/joy) in the full sample and 25 (spiritual/religious concerns) to 65
      % (meaning/joy) in a subsample of those within 2 years of HCT. The paired items
      of low meaning/joy and self-described R/S struggle attained a net sensitivity of
      82 % in the full sample and of 87 % in those within 2 years of HCT but with low
      net specificities. CONCLUSIONS: While no single-item screener was acceptable
      using our pre-specified sensitivity value of 85 %, the simultaneous use of
      meaning/joy and self-described struggle items among cancer survivors is currently
      the best choice to briefly screen for R/S distress. Future research should
      validate this and other approaches in active treatment cancer patients and
      survivors and determine the best times to screen.

PMID- 27714533
TI  - A method for predicting individual residue contributions to enzyme specificity
      and binding-site energies, and its application to MTH1.
AB  - A new method for predicting the energy contributions to substrate binding and to
      specificity has been developed. Conventional global optimization methods do not
      permit the subtle effects responsible for these properties to be modeled with
      sufficient precision to allow confidence to be placed in the results, but by
      making simple alterations to the model, the precisions of the various energies
      involved can be improved from about +/-2 kcal mol-1 to +/-0.1 kcal mol-1. This
      technique was applied to the oxidized nucleotide pyrophosphohydrolase enzyme
      MTH1. MTH1 is unusual in that the binding and reaction sites are well separated
      an advantage from a computational chemistry perspective, as it allows the
      energetics involved in docking to be modeled without the need to consider any
      issues relating to reaction mechanisms. In this study, two types of energy terms
      were investigated: the noncovalent interactions between the binding site and the
      substrate, and those responsible for discriminating between the oxidized
      nucleotide 8-oxo-dGTP and the normal dGTP. Both of these were investigated using
      the semiempirical method PM7 in the program MOPAC. The contributions of the
      individual residues to both the binding energy and the specificity of MTH1 were
      calculated by simulating the effect of mutations. Where comparisons were
      possible, all calculated results were in agreement with experimental
      observations. This technique provides fresh insight into the binding mechanism
      that enzymes use for discriminating between possible substrates.

PMID- 27714534
TI  - Calculations of BODIPY dyes in the ground and excited states using the M06-2X and
      PBE0 functionals.
AB  - A number of fluorescent dyes based on BODIPY (4,4'-difluoro-4-bora-3a,4a-diaza-s
      indacene) have been studied theoretically. This paper presents the results of
      calculations of these BODIPY dyes in their ground and excited states, performed
      using DFT and TD-DFT methods, respectively. The influences of N,N
      dimethylaminobenzyl, ortho-fluorophenol, and methyl substituents as well as the
      solvent polarity on the positions of the absorption and emission bands of the
      dyes were analyzed. The computational data obtained in this work were compared to
      the corresponding experimental data. The trends in the experimental data were
      found to agree with those shown by the computational data. Differences between
      the potential curves obtained when using linear-response (LR) and state-specific
      (SS) approaches for the ground and excited states are also reported. Graphical
      Abstract The article shows that the trends of the experimental dependencies
      lambdaabs = f(Deltaf) and lambdaem = f(Deltaf) well described by PBE0 (LR
      approach) and M06-2X (SS approach) calculations, respectively. The influence of
      substituents on the spectral characteristics of the BODIPY chromophore are
      analysed.

PMID- 27714535
TI  - Ultrastructural and physiological changes induced by different stress conditions
      on the human parasite Trypanosoma cruzi.
AB  - Trypanosoma cruzi is the etiological agent of Chagas disease. The life cycle of
      this protozoan parasite is digenetic because it alternates its different
      developmental forms through two hosts, a vector insect and a vertebrate host. As
      a result, the parasites are exposed to sudden and drastic environmental changes
      causing cellular stress. The stress response to some types of stress has been
      studied in T. cruzi, mainly at the molecular level; however, data about
      ultrastructure and physiological state of the cells in stress conditions are
      scarce or null. In this work, we analyzed the morphological, ultrastructural, and
      physiological changes produced on T. cruzi epimastigotes when they were exposed
      to acid, nutritional, heat, and oxidative stress. Clear morphological changes
      were observed, but the physiological conditions varied depending on the type of
      stress. The maintenance of the physiological state was severely affected by heat
      shock, acidic, nutritional, and oxidative stress. According to the surprising
      observed growth recovery after damage by stress alterations, different
      adaptations from the parasite to these harsh conditions were suggested.
      Particular cellular death pathways are discussed.

PMID- 27714536
TI  - Clinical outcomes of stage IV colorectal cancer after R0 resection: a multi
      institutional retrospective analysis.
AB  - BACKGROUND: We analyzed the treatment outcomes after curative surgery for stage
      IV colorectal cancer to develop outcome-based follow-up protocols and treatment
      strategies. METHODS: This study was a multi-institutional retrospective analysis
      of treatment outcomes in patients who underwent R0 surgery for stage IV
      colorectal cancer. RESULTS: A total of 1133 patients, of whom 837 had recurrence,
      were included in this study. Recurrence occurred within 12 and 24 months after R0
      surgery in 452 (54.0 %) and 652 (77.9 %) patients, respectively. Surgical
      resection was performed less frequently for recurrence within 12 months of R0
      surgery than for recurrence after more than 12 months (p = 0.003). Prognosis was
      significantly better in patients who had recurrence more than 24 months after R0
      surgery than in those who had recurrence within 24 months; this was not only for
      all patients but also specifically for patients with resection for recurrent
      disease. Recurrence was less frequent in patients who received preoperative
      chemotherapy than in patients who did not receive preoperative chemotherapy (p =
      0.04). Of significance, fewer patients who received preoperative chemotherapy
      (57.5 %) had recurrence within 24 months compared with patients who did not
      receive preoperative chemotherapy (79.8 %) (p = 0.00001). CONCLUSIONS: Intensive
      follow-up for at least 24 months was considered appropriate for monitoring
      disease recurrence after R0 surgery for stage IV colorectal cancer. In addition,
      preoperative chemotherapy contributed to improved outcomes.

PMID- 27714537
TI  - Erratum to: Imaging for Quality Control: Comparison of Systematic Video Recording
      to the Operative Note in Colorectal Cancer Surgery. A Pilot Study.

PMID- 27714538
TI  - Comparison of Salvage Total Pharyngolaryngectomy and Cervical Esophagectomy
      Between Hypopharyngeal Cancer and Cervical Esophageal Cancer.
AB  - BACKGROUND: Total pharyngolaryngectomy and cervical esophagectomy (TPLCE) after
      chemoradiotherapy remains a challenge because of the high rate of complications
      and few available data on outcomes and safety. The purpose of this study was to
      evaluate the clinical significance of salvage TPLCE and to compare treatment
      outcomes between hypopharyngeal cancer and cervical esophageal cancer. METHODS:
      Data from 37 consecutive patients who were diagnosed with potentially resectable
      hypopharyngeal and cervical esophageal cancer after chemoradiotherapy were
      retrospectively analyzed. The survival and surgical outcomes were investigated
      between the hypopharyngeal cancer and cervical esophageal cancer groups. RESULTS:
      Twenty-six patients were included in hypopharyngeal cancer group and 11 patients
      were included in cervical esophageal cancer group. The baseline characteristics
      were balanced between the two groups. Compared to the hypopharyngeal cancer
      group, the cervical esophageal cancer group had significantly more frequent
      tracheal-related complications (p < 0.05) and stronger association of distal
      margin of the cervical esophagus and radiation field with tracheal ischemia after
      salvage surgery. CONCLUSIONS: Salvage TPLCE can offer the exclusive chance of
      prolonged survival. Association of tracheal ischemia with salvage TPLCE was seen
      more frequently for cervical esophageal cancer. Therefore, the indication for
      salvage TPLCE must be carefully considered to maintain the balance between
      curability and safety.

PMID- 27714539
TI  - A Choice of Wine.

PMID- 27714540
TI  - Ultrasound-Guided Core-Needle Versus Vacuum-Assisted Breast Biopsy: A Cost
      Analysis Based on the American Society of Breast Surgeons' Mastery of Breast
      Surgery Registry.
AB  - PURPOSE: To evaluate the cost-efficacy of vacuum-assisted ultrasound-guided
      breast biopsy instruments compared to ultrasound-guided 14-gauge spring-loaded
      core-needle biopsy. METHODS: The American Society of Breast Surgeons' Mastery of
      Breast Surgery Registry was reviewed. Biopsy findings, any rebiopsy, and the
      instrument used were abstracted for 31,451 ultrasound-guided biopsy procedures
      performed between 2001 and July 2014. Rates of cancer diagnosis and rebiopsy were
      calculated for each instrument. A linear mathematical model was developed to
      calculate total cost per cancer diagnosis, including procedural costs and the
      costs of any additional surgical rebiopsy procedures. Mean cost per cancer
      diagnosis with confidence limits was then determined for 14-gauge spring-loaded
      core-needle biopsy and 14 different vacuum-assisted instruments. For 14-gauge
      spring-loaded core-needle biopsy, mean cost per cancer diagnosis was $4346 (4327
      $4366). For the vacuum-assisted instruments, mean cost per cancer diagnosis
      ranged from a low of $3742 ($3732-$3752) to a high of $4779 ($4750-$4809).
      RESULTS: Vacuum-assisted instruments overall were more cost-effective than core
      with a mean cost per cancer diagnosis of $4052 ($4038-$4067) (p < 0.05). Tethered
      vacuum-assisted instruments performed best with a mean cost per cancer diagnosis
      of $3978 ($3964-$3991) (p < 0.05). Nontethered devices had a mean cost per cancer
      diagnosis of $4369 ($4350-$4388), a result no better than core (p < 0.05).
      CONCLUSIONS: Ultrasound-guided vacuum-assisted breast biopsy had a lower mean
      cost per cancer diagnosis than 14-gauge spring-loaded core-needle biopsy. This
      advantage was only seen in tethered vacuum-assisted instruments. Within device
      families, larger instruments tended to outperform smaller instruments.

PMID- 27714542
TI  - Lower Bounds to the Reliabilities of Factor Score Estimators.
AB  - Under the general common factor model, the reliabilities of factor score
      estimators might be of more interest than the reliability of the total score (the
      unweighted sum of item scores). In this paper, lower bounds to the reliabilities
      of Thurstone's factor score estimators, Bartlett's factor score estimators, and
      McDonald's factor score estimators are derived and conditions are given under
      which these lower bounds are equal. The relative performance of the derived lower
      bounds is studied using classic example data sets. The results show that
      estimates of the lower bounds to the reliabilities of Thurstone's factor score
      estimators are greater than or equal to the estimates of the lower bounds to the
      reliabilities of Bartlett's and McDonald's factor score estimators.

PMID- 27714541
TI  - Cabozantinib for metastatic breast carcinoma: results of a phase II placebo
      controlled randomized discontinuation study.
AB  - PURPOSE: Cabozantinib (XL184), a multi-targeted oral tyrosine kinase inhibitor
      with activity against MET, VEGFR2, AXL, and other tyrosine kinases, was assessed
      in a cohort of metastatic breast cancer (MBC) patients in a phase II randomized
      discontinuation trial (RDT). METHODS: Patients received 100 mg cabozantinib daily
      during a 12-week lead-in stage. Those with stable disease per modified Response
      Evaluation Criteria in Solid Tumors version 1.0 at 12 weeks were randomized to
      either continue cabozantinib or receive placebo. Primary endpoints were objective
      response rate (ORR) during the 12-week lead-in stage and progression-free
      survival (PFS) after randomization. Patients were also followed for overall
      survival (OS). RESULTS: Forty-five patients with MBC and a median of three prior
      lines of chemotherapy for metastatic disease were enrolled. The ORR during the
      lead-in stage was 13.6 % (95 % confidence interval [CI] 6-25.7 %), and the
      disease control rate at week 12 was 46.7 % (95 % CI 31.7-61.6 %). Per the initial
      RDT study design, patients with stable disease at week 12 were randomized to
      cabozantinib or placebo. Following a Study Oversight Committee recommendation,
      randomization was suspended. Patients in the lead-in stage continued on open
      label cabozantinib. Patients in the randomization stage were subsequently
      unblinded. The overall median PFS for all MBC patients was 4.3 months. Median OS
      was 11.4 months (95 % CI 10.5-16.5 months). The most common grade 3/4 adverse
      events in the lead-in stage were palmar-plantar erythrodysesthesia (13 %) and
      fatigue (11 %). One death from respiratory failure was reported as drug-related
      during the lead-in stage. CONCLUSIONS: In heavily pretreated MBC patients,
      cabozantinib monotherapy demonstrated clinical activity including objective
      response and disease control.

PMID- 27714543
TI  - Functional Generalized Structured Component Analysis.
AB  - An extension of Generalized Structured Component Analysis (GSCA), called
      Functional GSCA, is proposed to analyze functional data that are considered to
      arise from an underlying smooth curve varying over time or other continua. GSCA
      has been geared for the analysis of multivariate data. Accordingly, it cannot
      deal with functional data that often involve different measurement occasions
      across participants and a large number of measurement occasions that exceed the
      number of participants. Functional GSCA addresses these issues by integrating
      GSCA with spline basis function expansions that represent infinite-dimensional
      curves onto a finite-dimensional space. For parameter estimation, functional GSCA
      minimizes a penalized least squares criterion by using an alternating penalized
      least squares estimation algorithm. The usefulness of functional GSCA is
      illustrated with gait data.

PMID- 27714544
TI  - A Procedure for Assessing the Completeness of the Q-Matrices of Cognitively
      Diagnostic Tests.
AB  - The Q-matrix of a cognitively diagnostic test is said to be complete if it allows
      for the identification of all possible proficiency classes among examinees.
      Completeness of the Q-matrix is therefore a key requirement for any cognitively
      diagnostic test. However, completeness of the Q-matrix is often difficult to
      establish, especially, for tests with a large number of items involving multiple
      attributes. As an additional complication, completeness is not an intrinsic
      property of the Q-matrix, but can only be assessed in reference to a specific
      cognitive diagnosis model (CDM) supposed to underly the data-that is, the Q
      matrix of a given test can be complete for one model but incomplete for another.
      In this article, a method is presented for assessing whether a given Q-matrix is
      complete for a given CDM. The proposed procedure relies on the theoretical
      framework of general CDMs and is therefore legitimate for CDMs that can be
      reparameterized as a general CDM.

PMID- 27714545
TI  - Clinical practice guideline for drug-induced kidney injury in Japan 2016: digest
      version.

PMID- 27714547
TI  - Downstairs My Father is Dying.

PMID- 27714546
TI  - Characterization and in vitro sensitivity of cholinesterases of gilthead seabream
      (Sparus aurata) to organophosphate pesticides.
AB  - The characterization of cholinesterase activity in brain and muscle of gilthead
      seabream was carried out using four specific substrates and three selective
      inhibitors. In addition, K m and V max were calculated from the Michaelis-Menten
      equation for ASCh and BSCh substrates. Finally, the in vitro sensitivity of brain
      and muscle cholinesterases to three organophosphates (OPs) was also investigated
      by estimating inhibition kinetics. The results indicate that AChE is the enzyme
      present in the brain, whereas in muscle, a typical AChE form is present along
      with an atypical form of BChE. Very low ChE activity was found in plasma with all
      substrates used. The inhibitory potency of the studied OPs on brain and muscle
      AChEs based on bimolecular inhibition constants (k i ) was: omethoate <
      dichlorvos < azinphosmethyl-oxon. Furthermore, muscle BChE was found to be
      several orders of magnitude (from 2 to 4) more sensitive than brain and muscle
      AChE inhibition by dichlorvos and omethoate.

PMID- 27714548
TI  - Microwave Assisted Synthesis, Optical Properties and Physicochemical
      Investigations on the Powerful Fluorophore: Donor (D) -pi-Acceptor (A) Chalcone.
AB  - (2E)-3-[4-(dimethylamino)phenyl]-1-(2-hydroxyphenyl)prop-2-en-1-one (DPHP) was
      synthesized by the reaction 4(dimethylamino) benzaldehyde with 1-(2
      hydroxyphenyl) ethanone under microwave irradiation. Structure of DPHP was
      conformed by 1H and 13C NMR, FT-IR, EI-MS spectral studies and elemental
      analysis. The electronic absorption and fluorescence spectra of DPHP have been
      studied in solvents of different polarities, and the data were used to study the
      solvatochromic properties such as extinction coefficient, stokes shift,
      oscillator strength, transition dipole moment, fluorescence quantum yield and
      photochemical quantum yield. The absorption maximum and fluorescence emission
      maximum was observed red shift when increase solvent polarity n-Hexane to DMF.
      DPHP undergoes solubilization in different micelles and may be used as a probe
      and quencher to determine the critical micelle concentration (CMC) of CTAB and
      SDS.

PMID- 27714550
TI  - Mapping face encoding using functional MRI in multiple sclerosis across disease
      phenotypes.
AB  - Using fMRI during a face encoding (FE) task, we investigated the behavioral and
      fMRI correlates of FE in patients with relapse-onset multiple sclerosis (MS) at
      different stages of the disease and their relation with attentive-executive
      performance and structural MRI measures of disease-related damage. A fMRI FE task
      was administered to 75 MS patients (11 clinically isolated syndromes - CIS, 40
      relapsing-remitting - RRMS - and 24 secondary progressive - SPMS) and 22 healthy
      controls (HC). fMRI activity during the face encoding condition was correlated
      with behavioral, clinical, neuropsychological and structural MRI variables. All
      study subjects activated brain regions belonging to face perception and encoding
      network, and deactivated areas of the default-mode network. Compared to HC, MS
      patients had the concomitant presence of areas of increased and decreased
      activations as well as increased and decreased deactivations. Compared to HC or
      RRMS, CIS patients experienced an increased recruitment of posterior-visual
      areas. Thalami, para-hippocampal gyri and right anterior cingulum were more
      activated in RRMS vs CIS or SPMS patients, while an increased recruitment of
      frontal areas was observed in SPMS vs RRMS. Areas of abnormal activations were
      significantly correlated with clinical, cognitive-behavioral and structural MRI
      measures. Abnormalities of FE network occur in MS and vary across disease
      clinical phenotypes. Early in the disease, an increased recruitment of areas
      typically devoted to face perception and encoding occurs. In SPMS patients,
      abnormal functional recruitment of frontal lobe areas might contribute to the
      severity of clinical manifestations.

PMID- 27714549
TI  - Systemic klotho is associated with KLOTHO variation and predicts intrinsic
      cortical connectivity in healthy human aging.
AB  - Cognitive decline is a major biomedical challenge as the global population ages.
      Elevated levels of the longevity factor klotho suppress aging, enhance cognition,
      and promote synaptic plasticity and neural resilience against aging and
      Alzheimer's disease (AD)-related pathogenic proteins. Here, we examined the
      relationship between human genetic variants of KLOTHO and systemic klotho levels 
      and assessed neuroanatomic correlates of serum klotho in a cohort of healthy
      older adults. Serum klotho levels were increased with KL-VS heterozygosity, as
      anticipated. We report, for the first time, that serum klotho levels were
      paradoxically decreased with KL-VS homozygosity. Further, we found that higher
      serum klotho levels were associated with measures of greater intrinsic
      connectivity in key functional networks of the brain vulnerable to aging and AD
      such as the fronto-parietal and default mode networks. Our findings suggest that
      elevated klotho promotes a resilient brain, possibly through increased network
      connectivity of critical brain regions.

PMID- 27714551
TI  - Cerebral perfusion alterations in type 2 diabetes and its relation to insulin
      resistance and cognitive dysfunction.
AB  - To explore the effect of T2DM on cerebral perfusion, and the relationship between
      cerebral perfusion changes and cognitive impairment as well as diabetic
      variables, by using a whole-brain arterial spin-labeling (ASL) MRI technique.
      This prospective study was approved by the local institutional review board and
      was performed between November 2012 and October 2013. All subjects provided
      informed consent. Forty T2DM patients and 41 age-, sex- and education-matched
      healthy controls were included. Cerebral blood flow (CBF) map was obtained by
      pulsed ASL perfusion imaging at 3 T MRI. Voxel-wise comparisons on CBF maps with
      and without partial volume effects (PVEs) correction were performed between
      groups. Associations between CBF and cognitive functioning, and between CBF and
      diabetic variables were investigated by using voxel-wise, whole-brain correlation
      analyses. In T2DM patients, PVEs uncorrected CBF was decreased in the posterior
      cingulate cortex (PCC), precuneus and bilateral occipital lobe, and increased in
      the anterior cingulate cortex (corrected P < .05). These changes were largely
      unchanged after PVEs correction. Correlation analyses revealed that in patients,
      hypoperfusion in PCC and precuneus regions were related to higher insulin
      resistance level and deficits in clock-drawing performance, while the occipital
      hypoperfusion was associated with worse visual-memory performance, regardless of
      PVEs correction. The cerebral hypoperfusion pattern in T2DM resembles the pattern
      observed in the early stage of dementia, and increased insulin resistance might
      be an important risk factor as well as treatment target for such CBF
      dysregulation.

PMID- 27714553
TI  - Beta-adrenergic antagonism modulates functional connectivity in the default mode
      network of individuals with and without autism spectrum disorder.
AB  - The beta-adrenergic antagonist propranolol benefits some social and communication
      domains affected in autism spectrum disorder (ASD), and these benefits appear to
      be associated with increased functional connectivity (FC) in the brain during
      task performance. FC is implicated in ASD, with the majority of studies
      suggesting long distance hypo-connectivity combined with regionally specific
      local hyper-connectivity. The objective in the current investigation was to
      examine the effect of propranolol on FC at rest and determine whether ASD
      specific effects exist. Participants with and without ASD attended three sessions
      in which propranolol, nadolol (a beta-adrenergic antagonist that does not cross
      the blood-brain barrier), or placebo were administered. Resting-state fMRI data
      were acquired, and graph theory techniques were utilized to assess additional
      aspects of FC. Compared to placebo, propranolol administration was associated
      with decreased FC in the dorsal medial prefrontal cortex subnetwork of the
      default mode network and increased FC in the medial temporal lobe subnetwork,
      regardless of diagnosis. These effects were not seen with nadolol suggesting that
      the alterations in FC following propranolol administration were not exclusively
      due to peripheral cardiovascular effects. Thus, beta-adrenergic antagonism can up
      or down- regulate FC, depending on the network, and alter coordinated functional
      activation in the brain. These changes in information processing, as demonstrated
      by FC, may mediate some of the clinical and behavioral effects of beta-adrenergic
      antagonism previously reported in patients with ASD.

PMID- 27714554
TI  - Intrinsic functional connectivity alterations in cognitively intact elderly APOE
      epsilon4 carriers measured by eigenvector centrality mapping are related to
      cognition and CSF biomarkers: a preliminary study.
AB  - Apolipoprotein E (APOE) epsilon4 allele is the best established genetic risk
      factor for sporadic Alzheimer's disease (AD). However, there is a need to
      understand the effects of this genotype on the brain by simultaneously assessing
      intrinsic brain network and cerebral spinal fluid (CSF) biomarkers changes in
      healthy older epsilon4 carriers. Thirteen cognitively intact, elderly APOE
      epsilon4 carriers and 22 epsilon3 homozygotes were included in the present study.
      Eigenvector centrality mapping (ECM) was used to identify brain network hub
      organization based on resting-state functional MRI (rsfMRI). We evaluated
      comprehensive cognitive ability and tested levels of Abeta1-42, total-tau (t-tau)
      and phosphorylated-tau (p-tau181) in CSF. Comparisons of ECM between two groups
      were conducted, followed by correlations analyses between EC values with
      significant group differences and cognitive ability/CSF biomarkers. APOE epsilon4
      carriers showed significantly decreased EC values in left medial temporal lobe
      (MTL), left lingual gyrus (LG) and increased EC values in left middle frontal
      gyrus (MFG) as compared to non-carriers. Correlation analysis demonstrated that
      left LG EC value correlated with Rey Auditory Verbal Learning Test total learning
      (RAVLT, r = 0.57, p < 0.05) and t-tau level (r = -0.57, p < 0.05), while left MFG
      EC values correlated with log-transformed Trail-Making Test B (TMT-B, r = -0.67,
      p < 0.05) in APOE epsilon4 carriers. This study suggests the APOE epsilon4 allele
      contributes to disruption of brain connectedness in certain functional nodes,
      which may result from neuronal death caused by toxicity of neurofibrillary
      tangles.

PMID- 27714552
TI  - Mapping temporo-parietal and temporo-occipital cortico-cortical connections of
      the human middle longitudinal fascicle in subject-specific, probabilistic, and
      stereotaxic Talairach spaces.
AB  - Originally, the middle longitudinal fascicle (MdLF) was defined as a long
      association fiber tract connecting the superior temporal gyrus and temporal pole
      with the angular gyrus. More recently its description has been expanded to
      include all long postrolandic cortico-cortical association connections of the
      superior temporal gyrus and dorsal temporal pole with the parietal and occipital
      lobes. Despite its location and size, which makes MdLF one of the most prominent
      cerebral association fiber tracts, its discovery in humans is recent. Given the
      absence of a gold standard in humans for this fiber tract, its precise and
      complete connectivity remains to be determined with certainty. In this study
      using high angular resolution diffusion MRI (HARDI), we delineated for the first
      time, six major fiber connections of the human MdLF, four of which are temporo
      parietal and two temporo-occipital, by examining morphology, topography, cortical
      connections, biophysical measures, volume and length in seventy brains.
      Considering the cortical affiliations of the different connections of MdLF we
      suggested that this fiber tract may be related to language, attention and
      integrative higher level visual and auditory processing associated functions.
      Furthermore, given the extensive connectivity provided to superior temporal gyrus
      and temporal pole with the parietal and occipital lobes, MdLF may be involved in
      several neurological and psychiatric conditions such as primary progressive
      aphasia and other aphasic syndromes, some forms of behavioral variant of
      frontotemporal dementia, atypical forms of Alzheimer's disease, corticobasal
      degeneration, schizophrenia as well as attention-deficit/hyperactivity Disorder
      and neglect disorders.

PMID- 27714555
TI  - Biocatalytic characterization of an endo-beta-1,4-mannanase produced by
      Paenibacillus sp. strain HY-8.
AB  - OBJECTIVES: To evaluate the biocatalytic characteristics of a new endo-beta-1,4-D
      mannan-degrading enzyme (ManP) from Paenibacillus sp. strain HY-8, a gut
      bacterium of the longicorn beetle Moechotypa diphysis. RESULTS: Purified ManP (32
      kDa) with an N-terminal amino acid sequence of APSFAVGADFSYVPG displayed the
      greatest degree of biocatalytic activity toward locust bean gum (LBG) at 55 
      degrees C and pH 7.0. The enzyme degraded LBG, guar gum, ivory nut mannan, and
      mannooligosaccharides (M2-M5), but did not exhibit any hydrolytic activity
      against structurally unrelated substrates. The biocatalytic activity of ManP
      against LBG and guar gum was 695 and 450 U mg-1, respectively. Especially,
      enzymatic hydrolysis of mannobiose yielded a mixture of mannose (16.6 %) and
      mannobiose (83.4 %), although the degree of mannobiose degradation by ManP with
      was relatively limited. CONCLUSION: The present results suggest that ManP is an
      endo-beta-1,4-mannanase and is distinct from various other characterized endo
      beta-1,4-mannanases.

PMID- 27714556
TI  - A reductase gene mppE controls yellow component production in azaphilone
      polyketide pathway of Monascus.
AB  - OBJECTIVES: To characterize a biosynthetic gene that is selectively involved in
      the biosynthesis of yellow or orange components in the azaphilone polyketide
      pathway of Monascus. RESULTS: A reductive modification is predicted to control
      the relative levels of reduced (yellow) and oxidized (orange and red) components
      in the pathway of azaphilone pigment biosynthesis in Monascus. Targeted
      inactivation of a reductase gene mppE enhanced orange and red pigment production
      whereas overexpression of the gene promoted yellow pigment production. The effect
      of mppE overexpression was dependent on culture methods, and augmented yellow
      pigmentation was evident in a submerged culture employing a chemically defined
      medium. CONCLUSIONS: MppE controls the biosynthesis of the yellow pigments,
      ankaflavin and monascin, as a reductive enzyme in the azaphilone polyketide
      pathway.

PMID- 27714557
TI  - Highly efficient transglycosylation of sialo-complex-type oligosaccharide using
      Coprinopsis cinerea endoglycosidase and sugar oxazoline.
AB  - OBJECTIVES: To establish an efficient method of chemoenzymatic modification for
      making N-linked oligosaccharide chains of glycoproteins structurally homogeneous,
      which crucially affects their bioactivities. RESULTS: Deglycosylated-RNase B
      (GlcNAc-RNase B; acceptor), sialylglyco (SG)-oxazoline (donor) and an N180H
      mutant of Coprinopsis cinerea endo-beta-N-acetylglucosaminidase (Endo-CCN180H)
      were employed. pH 7.5 was ideal for both SG-oxazoline's stability and Endo-CC's
      transglycosylation reaction. The most efficient reaction conditions for producing
      glycosylated-RNase B, virtually modified completely with sialo-biantennary-type
      complex oligosaccharide, were: 80 MUg GlcNAc-RNase B, 200 MUg SG-oxazoline and 3
      MUg Endo-CCN180H in 20 MUl 20 mM Tris/HCl pH 7.5 at 30  degrees C for 30-60 min.
      CONCLUSIONS: This transglycosylation method using SG-oxazoline and Endo-CCN180H
      is beneficial for producing pharmaceutical glycoproteins modified with homogenous
      biantennary-complex-type oligosaccharides.

PMID- 27714558
TI  - A novel trichosanthin fusion protein with increased cytotoxicity to tumor cells.
AB  - OBJECTIVE: To evaluate the anti-tumor effects of trichosanthin after fusion with
      a cell penetrating peptide, heparin-binding peptide (HBP), derived from human
      heparin-binding EGF-like growth factor (HB-EGF). RESULTS: The fusion protein of
      trichosanthin-HBP was expressed in Escherichia coli BL21 and purified by Ni-NTA
      affinity chromatography. The HBP domain had no influence on the topological
      inactivation activity and N-glycosidase activity of trichosanthin. Trichosanthin
      HBP significantly inhibited the growth of tested cancer cells which are
      impervious to trichosanthin. Tumor cell apoptosis and both the mitochondrial- and
      death receptor-mediated apoptotic signaling pathways induced by trichosanthin-HBP
      were more significant than those induced by trichosanthin in HeLa cells.
      CONCLUSION: HBP is an efficient intracellular delivery vehicle for trichosanthin
      and makes trichosanthin-HBP become a promising agent for cancer therapy.

PMID- 27714559
TI  - CaCO3 supplementation alleviates the inhibition of formic acid on
      acetone/butanol/ethanol fermentation by Clostridium acetobutylicum.
AB  - OBJECTIVE: To investigate the inhibiting effect of formic acid on
      acetone/butanol/ethanol (ABE) fermentation and explain the mechanism of the
      alleviation in the inhibiting effect under CaCO3 supplementation condition.
      RESULTS: From the medium containing 50 g sugars l-1 and 0.5 g formic acid l-1,
      only 0.75 g ABE l-1 was produced when pH was adjusted by KOH and fermentation
      ended prematurely before the transformation from acidogenesis to solventogenesis.
      In contrast, 11.4 g ABE l-1 was produced when pH was adjusted by 4 g CaCO3 l-1.
      The beneficial effect can be ascribed to the buffering capacity of CaCO3.
      Comparative analysis results showed that the undissociated formic acid
      concentration and acid production coupled with ATP and NADH was affected by the
      pH buffering capacity of CaCO3. Four millimole undissociated formic acid was the
      threshold at which the transformation to solventogenesis occurred. CONCLUSION:
      The inhibiting effect of formic acid on ABE fermentation can be alleviated by
      CaCO3 supplementation due to its buffering capacity.

PMID- 27714560
TI  - Barriers to Electronic Health Record Adoption: a Systematic Literature Review.
AB  - Federal efforts and local initiatives to increase adoption and use of electronic
      health records (EHRs) continue, particularly since the enactment of the Health
      Information Technology for Economic and Clinical Health (HITECH) Act. Roughly one
      in four hospitals not adopted even a basic EHR system. A review of the barriers
      may help in understanding the factors deterring certain healthcare organizations
      from implementation. We wanted to assemble an updated and comprehensive list of
      adoption barriers of EHR systems in the United States. Authors searched CINAHL,
      MEDLINE, and Google Scholar, and accepted only articles relevant to our primary
      objective. Reviewers independently assessed the works highlighted by our search
      and selected several for review. Through multiple consensus meetings, authors
      tapered articles to a final selection most germane to the topic (n = 27). Each
      article was thoroughly examined by multiple authors in order to achieve greater
      validity. Authors identified 39 barriers to EHR adoption within the literature
      selected for the review. These barriers appeared 125 times in the literature; the
      most frequently mentioned barriers were regarding cost, technical concerns,
      technical support, and resistance to change. Despite federal and local
      incentives, the initial cost of adopting an EHR is a common existing barrier. The
      other most commonly mentioned barriers include technical support, technical
      concerns, and maintenance/ongoing costs. Policy makers should consider incentives
      that continue to reduce implementation cost, possibly aimed more directly at
      organizations that are known to have lower adoption rates, such as small
      hospitals in rural areas.

PMID- 27714561
TI  - Estimation of Temporal Gait Events from a Single Accelerometer Through the Scale
      Space Filtering Idea.
AB  - The purpose of this paper is to develop an accelerometry system capable of
      performing gait event demarcation and calculation of temporal parameters using a
      single waist-mounted device. Particularly, a mobile phone positioned over the L2
      vertebra is used to acquire trunk accelerations during walking. Signals from the
      acceleration magnitude and the vertical acceleration are smoothed through
      different filters. Cut-off points between filtered signals as a result of
      convolving with varying levels of Gaussian filters and other robust features
      against temporal variation and noise are used to identify peaks that correspond
      to gait events. Five pre-frail older adults and five young healthy adults were
      recruited in an experiment. Cadence, step/stride time, step/stride CV, step
      asymmetry and percentages of the stance/swing and single/double support phases,
      among the two groups of different mobility were quantified by the system.

PMID- 27714562
TI  - Patient-Controlled Attribute-Based Encryption for Secure Electronic Health
      Records System.
AB  - In recent years, many countries have been trying to integrate electronic health
      data managed by each hospital to offer more efficient healthcare services. Since
      health data contain sensitive information of patients, there have been much
      research that present privacy preserving mechanisms. However, existing studies
      either require a patient to perform various steps to secure the data or restrict
      the patient to exerting control over the data. In this paper, we propose patient
      controlled attribute-based encryption, which enables a patient (a data owner) to
      control access to the health data and reduces the operational burden for the
      patient, simultaneously. With our method, the patient has powerful control
      capability of his/her own health data in that he/she has the final say on the
      access with time limitation. In addition, our scheme provides emergency medical
      services which allow the emergency staffs to access the health data without the
      patient's permission only in the case of emergencies. We prove that our scheme is
      secure under cryptographic assumptions and analyze its efficiency from the
      patient's perspective.

PMID- 27714563
TI  - Performance Analysis of Fuzzy-PID Controller for Blood Glucose Regulation in Type
      1 Diabetic Patients.
AB  - This paper presents Fuzzy-PID (FPID) control scheme for a blood glucose control
      of type 1 diabetic subjects. A new metaheuristic Cuckoo Search Algorithm (CSA) is
      utilized to optimize the gains of FPID controller. CSA provides fast convergence
      and is capable of handling global optimization of continuous nonlinear systems.
      The proposed controller is an amalgamation of fuzzy logic and optimization which
      may provide an efficient solution for complex problems like blood glucose
      control. The task is to maintain normal glucose levels in the shortest possible
      time with minimum insulin dose. The glucose control is achieved by tuning the PID
      (Proportional Integral Derivative) and FPID controller with the help of Genetic
      Algorithm and CSA for comparative analysis. The designed controllers are tested
      on Bergman minimal model to control the blood glucose level in the facets of
      parameter uncertainties, meal disturbances and sensor noise. The results reveal
      that the performance of CSA-FPID controller is superior as compared to other
      designed controllers.

PMID- 27714564
TI  - Heat shock protein-27 (HSP27) regulates STAT3 and eIF4G levels in first trimester
      human placenta.
AB  - During placental implantation, cytotrophoblast cells differentiate to
      extravillous trophoblast (EVT) cells that invade from the placenta into the
      maternal uterine blood vessels. The heat shock protein-27 (HSP27), the signal
      transducer and activator of transcription-3 (STAT3) and the eukaryotic
      translation initiation factor 4E (EIF4E) are involved in regulating EVT cell
      differentiation/migration. EIF4E and EIF4G compose the translation initiation
      complex, which is a major control point in protein translation. The molecular
      chaperone distinctiveness of HSP27 implies that it directly interferes with many
      target proteins. STAT3, EIF4E, and EIF4G were found to be HSP27 client proteins
      in tumor cells. We aimed to analyze if HSP27 regulate STAT3 and EIF4G levels in
      first trimester human placenta. We found that like STAT3, EIF4G is highly
      expressed in the EVT cells (immunohistochemistry). Silencing HSP27 in HTR-8/SVneo
      cells (siRNA, EVT cell line) and in placental explants reduced STAT3 level (47
      and 33 %, respectively, p < 0.05). HSP27 silencing reduced the levels of STAT3
      phosphorylation (33 % reduction, p < 0.05) and targets (IRF1, MUC1, MMP2/9 and
      EIF4E, 30-49 % reduction, p < 0.05) in the HTR-8/SVneo cells. Moreover, HSP27
      silencing significantly reduced EIF4G level and elevated the level of its
      fragments in HTR-8/SVneo cells and in the placental explants (p < 0.05). In
      conclusion, Placental implantation and development are accompanied by trophoblast
      cell proliferation and differentiation, which necessitates intense protein
      translation and STAT3 activation. HSP27 was found to be regulator of translation
      initiation and STAT3 level. Therefore, it suggests that HSP27 is a key protein
      during placental development and trophoblast cell differentiation.

PMID- 27714565
TI  - Asthma and Hypogammaglobulinemia: an Asthma Phenotype with Low Type 2
      Inflammation.
AB  - PURPOSE: Little is known about hypogammaglobulinemia (HGG) in asthma patients. No
      data are available on the characteristics of adult patients with asthma and HGG.
      METHODS: We conducted a retrospective monocentric study between January 2006 and
      December 2012. Asthma patients with a serum immunoglobulin (Ig) quantitative
      analysis were included and classified into two groups depending on their serum
      IgG concentration: presence or absence of HGG. Clinical, biological, functional,
      and radiologic characteristics were compared in univariate and multivariate
      analysis, using a logistic regression model. RESULTS: In univariate analysis,
      asthma patients with HGG (n = 25) were older (58 years old +/- 18 vs 49 +/- 18, p
      = 0.04) and more frequently active or former smokers as compared to patients with
      normoglobulinemia (n = 80) (56.0 vs 35.0 %, p = 0.01). Total IgE < 30 kUI/L was
      more frequently observed in patients with HGG (53.0 vs 18.3 %, p = 0.01). HGG
      asthma patients had lower fraction of exhaled nitric oxide (p = 0.02), blood
      eosinophilia (p = 0.0009), and presented with more severe composite score for
      bronchiectasis (p = 0.01). In multivariate analysis, asthma patients with HGG had
      increased risk of being smokers [OR = 6.11 (IC 95 % = 1.16-32.04)], having total
      IgE concentration < 30 kUI/L [OR = 12.87 (IC 95 % = 2.30-72.15)], and a more
      severe composite score of bronchiectasis [OR = 20.65 (IC 95 % = 2.13-199.74)].
      CONCLUSION: Asthma patients with HGG are older and more often tobacco smoker than
      asthma patients without HGG. These patients have low type-2 inflammation markers.

PMID- 27714566
TI  - Acquisition models in intraoperative positron surface imaging.
AB  - PURPOSE: Intraoperative imaging aims at identifying residual tumor during
      surgery. Positron Surface Imaging (PSI) is one of the solutions to help surgeons
      in a better detection of resection margins of brain tumor, leading to an improved
      patient outcome. This system relies on a tracked freehand beta probe, using
      [Formula: see text]F-based radiotracer. Some acquisition models have been
      proposed in the literature in order to enhance image quality, but no comparative
      validation study has been performed for PSI. METHODS: In this study, we
      investigated the performance of different acquisition models by considering
      validation criteria and normalized metrics. We proposed a reference-based
      validation framework to perform the comparative study between acquisition models
      and a basic method. We estimated the performance of several acquisition models in
      light of four validation criteria: efficiency, computational speed, spatial
      accuracy and tumor contrast. RESULTS: Selected acquisition models outperformed
      the basic method, albeit with the real-time aspect compromised. One acquisition
      model yielded the best performance among all according to the validation
      criteria: efficiency (1-Spe: 0.1, Se: 0.94), spatial accuracy (max Dice: 0.77)
      and tumor contrast (max T/B: 5.2). We also found out that above a minimum
      threshold value of the sampling rate, the reconstruction quality does not vary
      significantly. CONCLUSION: Our method allowed the comparison of different
      acquisition models and highlighted one of them according to our validation
      criteria. This novel approach can be extended to 3D datasets, for validation of
      future acquisition models dedicated to intraoperative guidance of brain surgery.

PMID- 27714567
TI  - Central X-ray beam correction of radiographic acetabular cup measurement after
      THA: an experimental study.
AB  - PURPOSE: Accurate assessment of cup orientation on postoperative radiographs is
      essential for evaluating outcome after THA. However, accuracy is impeded by the
      deviation of the central X-ray beam in relation to the cup and the impossibility
      of measuring retroversion on standard pelvic radiographs. METHOD: In an
      experimental trial, we built an artificial cup holder enabling the setting of
      different angles of anatomical anteversion and inclination. Twelve different cup
      orientations were investigated by three examiners. After comparing the two
      methods for radiographic measurement of the cup position developed by Lewinnek
      and Widmer, we showed how to differentiate between anteversion and retroversion
      in each cup position by using a second plane. To show the effect of the central
      beam offset on the cup, we X-rayed a defined cup position using a
      multidirectional central beam offset. According to Murray's definition of
      anteversion and inclination, we created a novel corrective procedure to balance
      measurement errors caused by deviation of the central beam. RESULTS: Measurement
      of the 12 different cup positions with the Lewinnek's method yielded a mean
      deviation of [Formula: see text] (95 % CI 1.3-2.3) from the original cup
      anteversion. The respective deviation with the Widmer/Liaw's method was [Formula:
      see text] (95 % CI 2.4-4.0). In each case, retroversion could be differentiated
      from anteversion with a second radiograph. Because of the multidirectional
      central beam offset ([Formula: see text] cm) from the acetabular cup in the cup
      holder ([Formula: see text] anteversion and [Formula: see text] inclination), the
      mean absolute difference for anteversion was [Formula: see text] (range [Formula:
      see text] to [Formula: see text] and [Formula: see text] (range [Formula: see
      text] to [Formula: see text] for inclination. The application of our novel
      mathematical correction of the central beam offset reduced deviation to a mean
      difference of [Formula: see text] for anteversion and [Formula: see text] for
      inclination. CONCLUSION: This novel calculation for central beam offset
      correction enables highly accurate measurement of the cup position.

PMID- 27714568
TI  - Louis Harold Gray (November 10, 1905-July 9, 1965): a pioneer in radiobiology.

PMID- 27714569
TI  - Optimal nonlinear cue integration for sound localization.
AB  - Integration of multiple sensory cues can improve performance in detection and
      estimation tasks. There is an open theoretical question of the conditions under
      which linear or nonlinear cue combination is Bayes-optimal. We demonstrate that a
      neural population decoded by a population vector requires nonlinear cue
      combination to approximate Bayesian inference. Specifically, if cues are
      conditionally independent, multiplicative cue combination is optimal for the
      population vector. The model was tested on neural and behavioral responses in the
      barn owl's sound localization system where space-specific neurons owe their
      selectivity to multiplicative tuning to sound localization cues interaural phase
      (IPD) and level (ILD) differences. We found that IPD and ILD cues are
      approximately conditionally independent. As a result, the multiplicative
      combination selectivity to IPD and ILD of midbrain space-specific neurons permits
      a population vector to perform Bayesian cue combination. We further show that
      this model describes the owl's localization behavior in azimuth and elevation.
      This work provides theoretical justification and experimental evidence supporting
      the optimality of nonlinear cue combination.

PMID- 27714571
TI  - Correlation of TLR4 and KLF7 in Inflammation Induced by Obesity.
AB  - Objective Recent studies have revealed a link between toll-like receptors (TLRs),
      Kruppel-like factors (KLFs), and the adipose tissue inflammation associated with
      obesity. TLR4 is associated with chronic inflammation in obesity. KLF7 is known
      to play an important role in the differentiation of adipocytes, but its role in
      visceral adipose tissue inflammation has not yet been investigated. Thus, the
      objective of this study was to determine the correlation of TLR4 and KLF7 in
      inflammation induced by obesity. Methods A total of 32 Wistar male rat subjects
      were fed in the center for experimental animals of Shihezi University. The rats
      were divided into normal control (NC) and high-fat diet (HFD) group. Surgical
      instruments were used to collect rats' visceral adipose tissue samples in the
      10th week after HFD feeding. Ninety-five Uygur subjects between 20 and 90 years
      old were enrolled in the present study. The subjects were divided into two
      groups: the normal control group (NC, 18.0 kg/m2 <= BMI <= 23.9 kg/m2, n = 50)
      and the obesity group (OB, BMI >= 28 kg/m2, n = 45), and visceral adipose tissue
      was collected from the subjects. Anthropometric and clinical parameters were
      measured using standard procedures; biochemical indices were detected using the
      glucose oxidase-peroxidase method and a standardized automatic biochemistry
      analyzer; the plasma levels of inflammatory factors and adipocytokines were
      measured by enzyme-linked immunosorbent assay (ELISA); the mRNA and protein
      expression levels of key genes involved in the inflammatory signaling pathway
      were measured by real-time PCR and Western blot. Results In rats, compared with
      the NC group, the weight, Lee's index, waist circumference, visceral fat mass,
      and the plasma level of Glu, TG, FFA, and TNF-alpha were higher in the HFD group,
      while the plasma levels of LPT and APN were significantly lower in the HFD group
      in the 10th week. Furthermore, compared with the NC group, visceral adipose
      tissue's mRNA expression levels of TLR4, KLF7, and SRC were higher in the HFD
      group, and KLF7 was significantly positively correlated with LDL, TLR4, SRC, and
      IL-6 (P < 0.05). Meanwhile, in the Uygur population, the plasma levels of TG,
      LDL, and TNF-alpha in the OB group were significantly higher than those in the NC
      group (P < 0.05). Moreover, compared with the NC group, visceral adipose tissue's
      mRNA expression levels of TLR4, KLF7, and SRC were significantly higher in the OB
      group (P < 0.05), and KLF7 was significantly positively correlated with TC, TLR4,
      MYD88, SRC, and IL-6 (P < 0.05); the protein expression levels of TLR4 and KLF7
      were significantly higher than those in the NC group (P < 0.05). Conclusion
      Higher expression of TLR4 and KLF7 may play a vital role in the process of
      inflammation induced by obesity in visceral adipose tissue.

PMID- 27714572
TI  - Wound stability and surgically induced corneal astigmatism after
      transconjunctival single-plane sclerocorneal incision cataract surgery.
AB  - PURPOSE: To compare intraocular pressure (IOP) immediately after cataract
      surgery, and surgically induced corneal astigmatism (SIA) and corneal shape
      changes between eyes with transconjunctival single-plane sclerocorneal incisions
      (TSSIs) and eyes with clear corneal incisions (CCIs). METHODS: Bilateral eyes of
      64 patients undergoing phacoemulsification were randomized to undergo 2.4-mm
      temporal TSSI or CCI. IOP was measured preoperatively, and in the immediate
      postoperative periods. SIA was determined using vector analysis, and corneal
      shape changes and irregular astigmatism were evaluated using a videokeratography
      preoperatively, and in the early postoperative periods. RESULTS: Wound hydration
      was performed in 23 eyes (35.9 %) of the TSSI group and in 60 (93.8 %) of the CCI
      group (P < 0.0001). Mean IOP was significantly higher in the TSSI group than in
      the CCI group at 30, 60, and 120 min postoperatively (P <= 0.0179). SIA tended to
      be smaller in the TSSI group than the CCI group, but the difference was not
      significant. The higher order irregular astigmatism was smaller in the TSSI group
      than in the CCI group at 2 days (P = 0.0312). The videokeratography revealed a
      wound-related flattening postoperatively in both groups; this change disappeared
      within 4 weeks in the TSSI group, whereas it persisted until 12 weeks in the CCI
      group. CONCLUSION: IOP was significantly higher immediately after TSSI than after
      CCI and required less wound hydration, suggesting better stability with TSSI.
      Higher order irregular astigmatism and wound-related corneal flattening were
      smaller after TSSI than after CCI in the early periods, suggesting that fewer
      corneal shape changes with TSSI.

PMID- 27714570
TI  - Mathematical Models for Immunology: Current State of the Art and Future Research
      Directions.
AB  - The advances in genetics and biochemistry that have taken place over the last 10
      years led to significant advances in experimental and clinical immunology. In
      turn, this has led to the development of new mathematical models to investigate
      qualitatively and quantitatively various open questions in immunology. In this
      study we present a review of some research areas in mathematical immunology that
      evolved over the last 10 years. To this end, we take a step-by-step approach in
      discussing a range of models derived to study the dynamics of both the innate and
      immune responses at the molecular, cellular and tissue scales. To emphasise the
      use of mathematics in modelling in this area, we also review some of the
      mathematical tools used to investigate these models. Finally, we discuss some
      future trends in both experimental immunology and mathematical immunology for the
      upcoming years.

PMID- 27714573
TI  - Subjective Cognitive Complaints and Objective Cognitive Function in Aging: A
      Systematic Review and Meta-Analysis of Recent Cross-Sectional Findings.
AB  - Research investigating how subjective cognitive complaints (SCCs) might reliably
      indicate impairments in objective cognitive functioning has produced highly
      varied findings, and despite attempts to synthesise this literature (e.g., Jonker
      et al. International Journal of Geriatric Psychiatry, 15, 983-991, 2000; Reid and
      MacLullich Dementia and Geriatric Cognitive Disorders, 22(5-6), 471-485, 2006;
      Crumley et al. Psychology and Aging, 29(2), 250-263, 2014), recent work continues
      to offer little resolution. This review provides both quantitative and
      qualitative synthesis of research conducted since the last comprehensive review
      in 2006, with the aim of identifying reasons for these discrepancies that might
      provide fruitful avenues for future exploration. Meta-analysis found a small but
      significant association between SCCs and objective cognitive function, although
      it was limited by large heterogeneity between studies and evidence of potential
      publication bias. Often, assessments of SCCs and objective cognitive function
      were brief or not formally validated. However, studies that employed more
      comprehensive SCC measures tended to find that SCCs were associated independently
      with both objective cognitive function and depressive symptoms. Further explicit
      investigation of how assessment measures relate to reports of SCCs, and the
      validity of the proposed 'compensation theory' of SCC aetiology, is recommended.

PMID- 27714574
TI  - D-Pinitol in Fabaceae: an Oviposition Stimulant for the Common Grass Yellow
      Butterfly, Eurema mandarina.
AB  - The common grass yellow butterfly, Eurema mandarina (formerly Eurema hecabe
      mandarina) (Lepidoptera, Pieridae), recently has been separated taxonomically
      from a subtropical population of Eurema hecabe in Japan. This species is widely
      distributed in the temperate region of Japan, and feeds mainly on various
      ligneous plants within the Fabaceae. We attempted to identify an oviposition
      stimulant for E. mandarina from its primary hosts, Albizia julibrissin and
      Lespedeza cuneata. In both hosts, crude extract and an aqueous fraction elicited
      oviposition responses from gravid females. A polar subfraction of the aqueous
      fraction also stimulated high oviposition-stimulatory activity, comparable to the
      original aqueous fraction, suggesting that E. mandarina females use water-soluble
      compounds for host recognition. Subsequent activity-directed fractionation by ion
      exchange chromatography indicated that one of the key substances was contained in
      the neutral/amphoteric fraction. Chemical analyses revealed that the active
      fractions of both hosts contained D-(+)-pinitol as the major component. We
      examined female responses to authentic D-pinitol and found that it induced
      oviposition responses at concentrations greater than 0.1 %. Since this cyclitol
      is omnipresent in Fabaceae, we conclude that D-pinitol plays a role in mediating
      oviposition of E. mandarina on fabaceous plants.

PMID- 27714575
TI  - AGEs/sRAGE, a novel risk factor in the pathogenesis of end-stage renal disease.
AB  - Interaction of advanced glycation end products (AGEs) with its cell-bound
      receptor (RAGE) results in cell dysfunction through activation of nuclear factor
      kappa-B, increase in expression and release of inflammatory cytokines, and
      generation of oxygen radicals. Circulating soluble receptors, soluble receptor
      (sRAGE), endogenous secretory receptor (esRAGE) and cleaved receptor (cRGAE) act
      as decoy for RAGE ligands and thus have cytoprotective effects. Low levels of
      sRAGE and esRAGE have been proposed as biomarkers for many diseases. However
      sRAGE and esRAGE levels are elevated in diabetes and chronic renal diseases and
      still tissue injury occurs. It is possible that increases in levels of AGEs are
      greater than increases in the levels of soluble receptors in these two diseases.
      Some new parameters have to be used which could be an universal biomarkers for
      cell dysfunction. It is hypothesized that increases in serum levels of AGEs are
      greater than the increases in the soluble receptors, and that the levels of AGEs
      is correlated with soluble receptors and that the ratios of AGEs/sRAGE,
      AGEs/esRAGE and AGEs/cRAGE are elevated in patients with end-stage renal disease
      (ESRD) and would serve as an universal risk marker for ESRD. The study subject
      comprised of 88 patients with ESRD and 20 healthy controls. AGEs, sRAGE and
      esRAGE were measured using commercially available enzyme linked immune assay
      kits. cRAGE was calculated by subtracting esRAGE from sRAGE. The data show that
      the serum levels of AGEs, sRAGE, cRAGE are elevated and that the elevation of
      AGEs was greater than those of soluble receptors. The ratios of AGEs/sRAGE,
      AGEs/esRAGE and AGEs/cRAGE were elevated and the elevation was similar in
      AGEs/sRAGE and AGEs/cRAGE but greater than AGEs/esRAGE. The sensitivity,
      specificity, accuracy, and positive and negative predictive value of AGEs/sRAGE
      and AGEs/cRAGE were 86.36 and 84.88 %, 86.36 and 80.95 %, 0.98 and 0.905, 96.2
      and 94.8 %, and 61.29 and 56.67 % respectively. There was a positive correlation
      of sRAGE with esRAGE and cRAGE, and AGEs with esRAGE; and negative correlation
      between sRAGE and AGEs/sRAGE, esRAGE and AGES/esRAGE, and cRAGE and AGES/cRAGE.
      In conclusion, AGEs/sRAGE, AGEs/cRAGE and AGEs/esRAGE may serve as universal risk
      biomarkers for ESRD and that AGEs/sRAGE and AGEs/cRAGE are better risk biomarkers
      than AGEs/esRAGE.

PMID- 27714579
TI  - Emerging Scholar Best Article Award, 2016.

PMID- 27714576
TI  - Comparison of the Adipose and Luminal Mammary Gland Compartment as Orthotopic
      Inoculation Sites in a 4T1-Based Immunocompetent Preclinical Model for Triple
      Negative Breast Cancer.
AB  - Breast tumorigenesis is classically studied in mice by inoculating tumor cells in
      the fat pad, the adipose compartment of the mammary gland. Alternatively, the
      mammary ducts, which constitute the luminal mammary gland compartment, also
      provide a suitable inoculation site to induce breast cancer in murine models. The
      microenvironments in these compartments influence tumor cell progression, yet
      this effect has not been investigated in an immunocompetent context. Here, we
      compared both mammary gland compartments as distinct inoculation sites, taking
      into account the immunological aspect by inoculating 4T1 tumor cells in
      immunocompetent mice. Following tumor cell inoculation in the adipose compartment
      of non-pretreated/naive, hormonally pretreated/naive and non-pretreated/lactating
      mice, the primary tumors developed similarly. However, a slower onset of primary
      tumor growth was found after inoculations in the luminal compartment of non
      pretreated/lactating mice. Despite this difference in tumor development rate,
      metastasis to the liver and lungs was equally observed and was accompanied by
      lymphatic spreading of tumor cells and progressive splenomegaly with both
      inoculation types. Chitinase 3-like 1 (CHI3L1) and lipocalin 2 (LCN2) served as
      innovative biomarkers for disease progression showing increased levels in primary
      tumors and sera of the non-pretreated/lactating inoculation groups. A slower
      increase in circulating CHI3L1 but not LCN2 levels, was observed after
      inoculations in the luminal compartment which corroborated the slower tumor
      development at this inoculation site. Our results highlight the critical impact
      of different mammary gland compartments on tumor development in syngeneic murine
      models and support the use of novel tumor progression biomarkers in an immune
      competent environment.

PMID- 27714580
TI  - Diabetes and Bone Marrow Adiposity.
AB  - PURPOSE OF REVIEW: This study aims to describe bone marrow fat changes in
      diabetes and to discuss the potential role of marrow fat in skeletal fragility.
      RECENT FINDINGS: Advances in non-invasive imaging have facilitated marrow fat
      research in humans. In contrast to animal studies which clearly demonstrate
      higher levels of marrow fat in diabetes, human studies have shown smaller and
      less certain differences. Marrow fat has been reported to correlate with A1c, and
      there may be a distinct marrow lipid saturation profile in diabetes. Greater
      marrow fat is associated with impaired skeletal health. Marrow fat may be a
      mediator of skeletal fragility in diabetes. Circulating lipids, growth hormone
      alterations, visceral adiposity, and hypoleptinemia have been associated with
      greater marrow fat and may represent potential mechanisms for the putative
      effects of diabetes on marrow fat, although other factors likely contribute.
      Additional research is needed to further define the role of marrow fat in
      diabetic skeletal fragility and to determine whether marrow fat is a therapeutic
      target.

PMID- 27714582
TI  - Galactose alters markers of oxidative stress and acetylcholinesterase activity in
      the cerebrum of rats: protective role of antioxidants.
AB  - We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on
      thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content,
      protein carbonyl content, on the activities of the antioxidant enzymes catalase
      (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on
      acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and
      hippocampus of rats. We also investigated the influence of the antioxidants (each
      at 1 mM), alpha-tocopherol, ascorbic acid and glutathione, on the effects
      elicited by galactose on the parameters tested. Results showed that galactose, at
      a concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral
      cortex and cerebellum of rats. In the cerebral cortex, galactose at
      concentrations of 5.0 and 10.0 mM increased TBA-RS and protein carbonyl content,
      and at 10.0 mM increased CAT activity and decreased AChE activity. In the
      cerebellum, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD
      and GSH-Px activities. In the hippocampus, galactose at concentrations of 5.0 and
      10.0 mM increased TBA-RS and CAT activity and at 10.0 mM decreased GSH-Px. Data
      showed that at the pathologically high concentration (greater than 5.0 mM),
      galactose induces lipid peroxidation, protein carbonylation, alters antioxidant
      defenses in the cerebrum, and also alters cholinesterase activity. Trolox,
      ascorbic acid and glutathione addition prevented the majority of alterations in
      oxidative stress parameters and the decrease in AChE activity that were caused by
      galactose. Our findings lend support to a potential therapeutic strategy for this
      condition, which may include the use of appropriate antioxidants for ameliorating
      the damage caused by galactose.

PMID- 27714581
TI  - Finite Element-Based Mechanical Assessment of Bone Quality on the Basis of In
      Vivo Images.
AB  - Beyond bone mineral density (BMD), bone quality designates the mechanical
      integrity of bone tissue. In vivo images based on X-ray attenuation, such as CT
      reconstructions, provide size, shape, and local BMD distribution and may be
      exploited as input for finite element analysis (FEA) to assess bone fragility.
      Further key input parameters of FEA are the material properties of bone tissue.
      This review discusses the main determinants of bone mechanical properties and
      emphasizes the added value, as well as the important assumptions underlying
      finite element analysis. Bone tissue is a sophisticated, multiscale composite
      material that undergoes remodeling but exhibits a rather narrow band of tissue
      mineralization. Mechanically, bone tissue behaves elastically under physiologic
      loads and yields by cracking beyond critical strain levels. Through adequate cell
      orchestrated modeling, trabecular bone tunes its mechanical properties by volume
      fraction and fabric. With proper calibration, these mechanical properties may be
      incorporated in quantitative CT-based finite element analysis that has been
      validated extensively with ex vivo experiments and has been applied increasingly
      in clinical trials to assess treatment efficacy against osteoporosis.

PMID- 27714583
TI  - Insights from extracellular matrix studies in the hypothalamus: structural
      variations of perineuronal nets and discovering a new perifornical area of the
      anterior hypothalamus.
AB  - The hypothalamus controls metabolism, stress responses, and instinctive behaviors
      for individual survival and species preservation. Recent studies suggest that
      hypothalamic neurons retain plasticity throughout adulthood, which enables these
      neurons to respond to various kinds of changes in environment, nutrients, and
      fluctuating hormones. One of the mechanisms underlying the regulation of neural
      plasticity is the formation of a stable extracellular matrix (ECM) structure
      called perineuronal nets (PNNs). PNNs are large aggregates of heterogeneous ECM
      molecules such as chondroitin sulfate proteoglycans (CSPGs), hyaluronan, their
      link proteins, and tenascin-R. PNNs surround the cell body and proximal dendrites
      of a subset of neurons and limit adult neural plasticity. This review describes
      the CSPG-based ECM, including the PNNs, with a special focus on the hypothalamus
      of mice. We first provide an overview of PNNs in terms of their structure,
      molecular components, and functions, most of which have been demonstrated by
      extrahypothalamic studies. Second, we show the presence or absence of PNNs within
      individual hypothalamic regions and then describe non-PNN-formed ECM containing
      CSPGs that can be observed in particular hypothalamic regions. Finally, we will
      introduce a newly identified mouse hypothalamic area that we named the
      perifornical area of the anterior hypothalamus (PeFAH), which contains a cluster
      of PNN-positive neurons. PeFAH neurons express enkephalin and have bidirectional
      connections with the lateral septum. The anterior hypothalamus and lateral septum
      are thought to regulate defensive behaviors; therefore, the PeFAH neurons and
      PNNs around them could be involved in the regulation of defensive behaviors.

PMID- 27714585
TI  - Dementia Research Australia: the Australian Dementia Research Development
      Fellowship Program.

PMID- 27714584
TI  - Contemporary management of ST-segment elevation myocardial infarction.
AB  - ST-elevation myocardial infarction (STEMI), which constitutes nearly 25-40 % of
      current acute myocardial infarction (AMI) cases, is a medical emergency that
      requires prompt recognition and treatment. Since the 2013 STEMI practice
      guidelines, a wealth of additional data that may further advance optimal STEMI
      practices has emerged. These data highlight the importance of improving patient
      treatment and transport algorithms for STEMI from non-primary percutaneous
      coronary intervention (PCI) centers. In addition, a focus on the reduction of
      total pain-to-balloon (P2B) times rather than simply door-to-balloon (D2B) times
      may further improve outcomes after primary PCI for STEMI. The early
      administration of newer oral P2Y12 inhibitors, including crushed forms of these
      agents for faster absorption, represents another treatment advancement. Recent
      data also suggest avoiding concurrent morphine use due to interactions with P2Y12
      inhibitors. Furthermore, new technological advancements and investigational
      therapies, including Bioresorbable Vascular Scaffolds and the use of pre
      intervention intravenous microbubbles with transthoracic ultrasound, hold promise
      to play a useful role in future STEMI care. Despite these advancements, the
      prompt recognition of STEMI, at both the patient and health care system level,
      remains the cornerstone of optimal treatment.

PMID- 27714586
TI  - FCG (FLIPI, Charlson comorbidity index, and histological grade) score is superior
      to FLIPI in advanced follicular lymphoma.
AB  - The Follicular Lymphoma International Prognostic Index (FLIPI) is widely used in
      the identification of risk groups among follicular lymphoma (FL) patients. The
      aim of the present study was to evaluate the prognostic value of FLIPI combined
      with the Charlson comorbidity index (CCI) and histological grade of lymphoma. 224
      newly diagnosed FL patients (median age 56 years) treated with immunochemotherapy
      were retrospectively analysed. Low FLIPI had 21.0 % of patients, intermediate
      28.1 % and high 46.9 %. 50.9 % of patients had no comorbidities. Only 7.1 % of
      patients had a high CCI score (>=2), while 25.9 % of patients were histological
      grade 3. Parameters that influenced overall survival were evaluated using Cox
      regression analysis, in which CCI, FLIPI and histological grade (p < 0.05)
      retained prognostic significance. By combining these parameters, we have
      developed the FCG score, which incorporates FLIPI, CCI, and histological grade.
      This score defines three risk categories (low: 41.5 %; intermediate: 37.5 %;
      high: 13.4 %), associated with significantly different survival (p < 0.0001);
      this consequently improves discriminative power by 9.1 % compared to FLIPI. FCG
      score represents a possible new prognostic index, highlighting the role of the
      patient's clinical state and the histological characteristics of disease, as
      indicated by comorbidity index and histological grade of lymphoma.

PMID- 27714588
TI  - Cancer Screening Among Patients Who Self-Identify as Muslim: Combining Self
      Reported Data with Medical Records in a Family Practice Setting.
AB  - Cancer screening is a core component of family medicine but screening
      inequalities are well documented in Canada for foreign-born persons. Although
      people of Muslim faith and culture are the fastest growing immigrant population
      in Canada, there is little information in the literature about their cancer
      screening practices. Determining screening gaps could inform practice-based
      quality improvement initiatives. We conducted a retrospective chart review
      combining patient-level medical record data with self-reported religious
      affiliation to examine the relationship between religion and cancer screening in
      a large multi-site urban family practice. Religious affiliation was classified as
      Muslim, other affiliation, or atheist/no religious affiliation. 5311 patients
      were included in the study sample. Muslim patients were significantly less likely
      to prefer English for spoken communication than the other two groups, less likely
      to be Canadian-born, more likely to have a female family physician, and were over
      represented in the lowest income quintile. Muslim women were most likely to be up
      to-date on breast cancer screening (85.2 vs. 77.5 % for those with other
      religions vs. 69.5 % for those with no religious affiliation). There were no
      significant differences in cancer screening by physician sex. In this pilot study
      conducted within a primary care practice, we used self-reported data on religious
      affiliation to examine possible inequities in cancer screening and observed
      intriguing variations in screening by self-identified religious affiliation.
      Future efforts to collect and use similar patient-level data should incorporate
      non-official languages and intensively outreach to patients with less health
      system contact. Regardless, the family medicine context may be the ideal setting
      to collect and act on patient-level sociodemographic data such as religious
      affiliation.

PMID- 27714587
TI  - Japanese phase II study of rituximab maintenance for untreated indolent B-cell
      non-Hodgkin lymphoma with high tumor burden.
AB  - Recent large-scale randomized clinical trials in Europe and the US demonstrated
      that maintenance therapy with rituximab significantly improved the progression
      free survival (PFS) in indolent B-cell non-Hodgkin lymphoma (B-NHL) patients,
      especially those with follicular lymphoma (FL). However, rituximab maintenance
      has not been approved in Japan, because there are no clinical data supporting the
      benefit of rituximab maintenance in Japanese patients. Therefore, we conducted a
      single-arm, multicenter bridging study in previously untreated indolent B-NHL
      patients with high tumor burden. The primary endpoint was 4-year PFS and was
      expected to be 70 % based on previous studies. Sixty-two patients, including 55
      FL patients, were enrolled and received induction therapy with CHOP combined with
      rituximab (R-CHOP). Fifty-eight patients responding to R-CHOP induction received
      rituximab at 375 mg/m2 every 8 weeks for 2 years as for the rituximab maintenance
      arm in the PRIMA study. A 4-year PFS of 69.8 % was obtained (95 % confidence
      interval 55.9-80.0 %). Rituximab maintenance was well tolerated and common
      adverse events were infections, neutropenia, and/or leukopenia that were
      manageable with conventional supportive care. No patients died. These data were
      compatible with the PRIMA data. R-CHOP induction followed by rituximab is useful
      in Japanese patients with untreated indolent B-NHL having high tumor burden.
      Clinical trial number UMIN000001191.

PMID- 27714589
TI  - Expression of Two Novel beta-Glucosidases from Chaetomium atrobrunneum in
      Trichoderma reesei and Characterization of the Heterologous Protein Products.
AB  - Two novel GH3 family thermostable beta-glucosidases from the filamentous fungus
      Chaetomium atrobrunneum (CEL3a and CEL3b) were expressed in Trichoderma reesei,
      purified by two-step ion exchange chromatography, and characterized. Both enzymes
      were active over a wide range of pH as compared to Neurospora crassa beta
      glucosidase GH3-3, which was also expressed in T. reesei and purified. The
      optimum temperature of both C. atrobrunneum enzymes was around 60  degrees C at
      pH 5, and both enzymes had better thermal and pH stability and higher resistance
      to metallic compounds and to glucose inhibition than GH3-3. They also showed
      higher activity against oligosaccharides composed of glucose units and linked
      with beta-1,4-glycosidic bonds and moreover, had higher affinity for cellotriose
      over cellobiose. In hydrolysis tests against Avicel cellulose and steam-exploded
      sugarcane bagasse, performed at 45  degrees C, particularly the CEL3a enzyme
      performed similarly to N. crassa GH3-3 beta-glucosidase. Taking into account the
      thermal stability of the C. atrobrunneum beta-glucosidases, they both represent
      promising alternatives as enzyme mixture components for improved cellulose
      saccharification at elevated temperatures.

PMID- 27714590
TI  - Technical and clinical validation of three commercial real-time PCR kits for the
      diagnosis of neuroborreliosis in cerebrospinal fluid on three different real-time
      PCR platforms.
AB  - This study reports the evaluation of the technical and clinical validation of the
      O-DiaBorburg kit (DIA), Borrelia burgdorferi PCR kit, ISEX (GENE), and Borrelia
      burgdorferi sensu lato Real-TM (SAC) for the diagnosis of neuroborreliosis in
      cerebrospinal fluid based on both Borrelia DNA and CSF samples from patients with
      clinical suspicion of neuroborreliosis. This validation study was done by
      analysing the kits on the Rotorgene Q (RGQ), CFX96, and LightCycler480 (LC480).
      For all kits, the linear range was larger on RGQ than on CFX96 and LC480. A good
      reproducibility was obtained for all assays on all instruments. Storage at -20 
      degrees C resulted in a decreased reproducibility for SAC. Results of the limit
      of detection (LOD95) experiments indicated a better sensitivity than described in
      the kit insert for all kits on all PCR platforms. No cross-reactivity was found
      for genetically related organisms nor for other pathogens which may be present in
      CSF. All species of the Borrelia burgdorferi sensu lato complex were detected
      with the GENE and SAC kits. The DIA kit failed to detect B. lusitaniae. The
      results seemed to indicate a better overall performance for the GENE kit on RGQ.
      However, its diagnostic value could not be confirmed in the clinical validation
      study, wherein none of the 103 CSF samples from clinical neuroborreliosis cases
      showed a positive real-time PCR result with the GENE kit analysed on RGQ.

PMID- 27714591
TI  - Mitogen-activated protein kinases (MAPKs) are modulated during Francisella
      tularensis infection, but inhibition of extracellular-signal-regulated kinases
      (ERKs) is of limited therapeutic benefit.
AB  - Francisella tularensis is a Gram-negative intracellular bacterium that causes the
      disease tularemia. The disease can be fatal if left untreated and there is
      currently no licenced vaccine available; the identification of new therapeutic
      targets is therefore required. Toll-like receptors represent an interesting
      target for therapeutic modulation due to their essential role in generating
      immune responses. In this study, we analysed the in vitro expression of the key
      mitogen-activated protein kinases (MAPKs) p38, JNK and ERK in murine alveolar
      macrophages during infection with F. tularensis. The phosphorylation profile of
      ERK highlighted its potential as a target for therapeutic modulation and
      subsequently the effect of ERK manipulation was measured in a lethal intranasal
      F. tularensis in vivo model of infection. The selective ERK1/2 inhibitor
      PD0325901 was administered orally to mice either pre- or post-challenge with F.
      tularensis strain LVS. Both treatment regimens selectively reduced ERK
      expression, but only the pre-exposure treatment produced decreased bacterial
      burden in the spleen and liver, which correlated with a significant reduction in
      the pro-inflammatory cytokines IFN-gamma, MCP-1, IL-6, and TNF-alpha. However, no
      overall improvements in survival were observed for treated animals in this study.
      ERK may represent a useful therapeutic target where selective dampening of the
      immune response (to control the damaging pathology seen during infection) is
      combined with antibiotic treatment required to eradicate bacterial infection.
      This combination treatment strategy has been shown to be effective in other
      models of tularemia.

PMID- 27714592
TI  - Characteristics of cefazolin inoculum effect-positive methicillin-susceptible
      staphylococcus aureus infection in a multicentre bacteraemia cohort.
AB  - Cefazolin treatment failure has been observed in high-inoculum infections caused
      by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum
      effect (CIE). However, data on the characteristics and risk factors for the
      acquisition of CIE-positive MSSA infection are scarce. CIE positivity was
      measured as an MIC >= 16 MUg/ml with a high inoculum (~5 * 107 CFU/ml). The blaZ
      gene type was assessed through sequence analysis. The clinical characteristics
      and risk factors for the acquisition of CIE-positive MSSA infection were
      assessed. The association between the antimicrobial susceptibility profile and
      CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their
      corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates
      showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No
      significant association was found between CIE positivity and the site of
      infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10-7.48) and recent (<=1
      month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76
      12.50) were identified as significant risk factors for CIE-positive MSSA
      infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95
      % CI, 1.62-7.80) and erythromycin (OR 5.00, 95 % CI, 2.50-9.99) were associated
      with CIE positivity, presenting high specificity (92.9 %) and a negative
      predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth
      of MSSA bacteraemia cases. Although CIE positivity was not clinically
      discernible, CIE positivity was associated with clindamycin or erythromycin
      susceptibility. Therefore, our findings suggest that cefazolin can be used in the
      treatment of high-inoculum MSSA infection if the isolates are susceptible to
      clindamycin or erythromycin.

PMID- 27714593
TI  - Emergence of New Delhi metallo-beta-lactamase 1 and other carbapenemase-producing
      Acinetobacter calcoaceticus-baumannii complex among patients in hospitals in Ha
      Noi, Viet Nam.
AB  - Acinetobacter baumannii is an important cause of multidrug-resistant hospital
      acquired infections in the world. Here, we investigate the presence of NDM-1 and
      other carbapenemases among carbapenem-resistant A. baumannii isolated between
      August 2010 and December 2014 from three large hospitals in Hanoi, Vietnam. We
      identified 23/582 isolates (4 %) (11 from hospital A, five from hospital B, and
      seven from hospital C) that were NDM-1 positive, and among them 18 carried
      additional carbapenemase genes, including seven isolates carrying NDM-1, IMP-1,
      and OXA-58 with high MICs for carbapenems. Genotyping indicated that NDM-1
      carrying A. baumannii have expanded clonally in these hospitals. Five new STs
      (ST1135, ST1136, ST1137, ST1138, and ST1139) were identified. One isolate carried
      NDM-1 on a plasmid belonging to the N-repA replicon type; no NDM-1-positive
      plasmids were identified in the other isolates. We have shown the extent of the
      carbapenem resistance and the local clonal spread of A. baumannii carrying NDM-1
      in these hospitals; coexistence of NDM-1 and IMP-1 is reported for the first time
      from Vietnam here, and this will further seriously limit future therapeutic
      options.

PMID- 27714594
TI  - Rapid diagnostic test and use of antibiotic against methicillin-resistant
      Staphylococcus aureus in adult intensive care unit.
AB  - Ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus
      aureus (MRSA) is associated with excess mortality and costs. Molecular biology
      test allows rapid identification of MRSA in sputum with high negative predictive
      value. We hypothesized that use of a rapid diagnostic test in patients with
      suspected VAP was associated with reduced use of antibiotics directed against
      MRSA. This retrospective, observational study was conducted in a polyvalent
      intensive care unit (ICU) of a university hospital. We compared two periods:
      before (2007-2010) and after (2010-2015) the implementation of a rapid diagnostic
      test, which uses RT-PCR to detect pathogens in 60 minutes. The primary endpoint
      was the effect on the empirical use of anti-MRSA antibiotics. The second endpoint
      was the effect of this strategy on the cost regarding antibiotic treatment. The
      first group included 120 suspected VAP (88 patients) and the second group 121
      suspected VAP (89 patients). Empirical use of vancomycin and linezolid decreased
      by 50 % between the two periods. Twenty-seven VAP (22 %) were treated with an
      anti-MRSA treatment between 2007 and 2010, and 13 (11 %) between 2010 and 2015 (p
      = 0.04). The mean cost of anti-MRSA treatment by patients in the first group was
      63 +/- 223 ?, and 13 +/- 52 ? in the second group (p < 0.001). This study shows
      that a rapid diagnostic test was associated with reduced use and cost of anti
      MRSA antibiotics in patients with suspected VAP. These results should be
      confirmed by further multicenter prospective studies.

PMID- 27714595
TI  - Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam is Effective,
      Independent of Body Mass Index and the Extent and Severity of Psoriasis.
AB  - INTRODUCTION: Good treatment adherence is important in the effective management
      of psoriasis and is related to both the frequency of applications and the amount
      of product used versus the recommended dose. The efficacy and safety of fixed
      combination calcipotriol 50 ug/g (Cal) and betamethasone 0.5 mg/g as dipropionate
      (BD) in the treatment of psoriasis is well established; an aerosol foam
      formulation has been developed to enhance adherence. This subanalysis from the
      Phase III PSO-FAST study evaluates the amount of Cal/BD foam used during
      treatment and the association between the extent and severity of baseline
      disease. METHODS: Patients (>=18 years) with mild-to-severe body psoriasis were
      randomized 3:1 to once-daily Cal/BD foam or vehicle. The amount of Cal/BD foam
      and vehicle used over the 4-week study period was evaluated according to three
      baseline disease assessments: extent of body surface area (BSA) affected by
      psoriasis, physician's global assessment of disease severity (PGA) and modified
      psoriasis area and severity index (mPASI). Treatment success and mPASI75 rates
      were assessed according to body mass index (BMI) and body weight. RESULTS: 323
      patients were randomized to Cal/BD foam and 103 to vehicle. At week 4, the mean
      total amount of Cal/BD foam used was 120.8 g (n = 293), which was similar to the
      amount of vehicle used (128.9 g; n = 98). The total amount of Cal/BD foam used at
      week 4 was greater with increasing BSA and increasing severity of baseline PGA
      and mPASI. Throughout the study, 93.1% of patients in the Cal/BD foam group and
      99.0% of patients in the vehicle group missed <=10% of treatment applications.
      Treatment success and mPASI75 rates were generally similar when stratified
      according to BMI and body weight. CONCLUSIONS: This subanalysis demonstrates that
      Cal/BD aerosol foam is used appropriately and is effective for the treatment of
      psoriasis, independent of BMI and the extent or severity of disease. CLINICAL
      TRIALS NUMBER: NCT01866163. FUNDING: LEO Pharma A/S.

PMID- 27714596
TI  - Analysis of the Appendicularia class (subphylum Urochordata) as a possible tool
      for biomonitoring four estuaries of the tropical region.
AB  - This study aims to characterize the differences between physical and chemical
      parameters of water quality indicators and eutrophication in four estuaries of
      the state of Rio de Janeiro and relate them to full density of the species that
      belong to the Appendicularia class with the purpose of seeking bioindicators for
      estuarine areas. The estuaries studied were from the rivers Macae, Sao Joao,
      Bracui, and Pereque-Acu. The physicochemical parameters monitored for evaluation
      of the water bodies and used for the correlation with the appendicularians were
      pH, temperature, nitrite, nitrate, N-ammonia, total nitrogen, phosphate, total
      phosphorus, dissolved oxygen (DO), suspended particulate matter (SPM),
      chlorophyll a, heterotrophic bacteria, and fecal coliform. The estuaries Bracui
      and Sao Joao showed enhanced qualities of water and lower degrees of
      eutrophication than Macae and Pereque-Acu estuaries. The species of the
      Appendicularia class found in this study were Oikopleura longicauda (Vogt, 1854),
      Oikopleura dioica Fol, 1872, Oikopleura fusiformis Fol, 1872, and Fritillaria
      haplostoma Fol, 1872. The density of appendicularians and O. longicauda was
      inversely related to the nutrient values and SPM; nonetheless, no species of
      appendicularians could be used as a bioindicator of any estuary in the current
      study. Studies on the quality of estuary waters and the search for other
      bioindicators belonging to other zooplankton groups are recommended to confirm
      the obtained results and to expand the knowledge of these coastal environments.

PMID- 27714598
TI  - ?

PMID- 27714597
TI  - Biomonitoring and exposure assessment of people living near or working at an
      Italian waste incinerator: methodology of the SPoTT study.
AB  - Only few studies on the health effect of waste incinerators were focused on human
      biomonitoring (HBM). Our aim is to describe a protocol for assessing early
      variation of selected items in a population group living close to a waste
      incinerator in Turin, Italy. A cohort of 394 subjects was randomly selected,
      among residents near the incinerator and residents far from it. To achieve this
      sample size, 765 subjects were contacted. The cohort was monitored before the
      start-up of the plant and will be followed up 1 and 3 years after, with
      measurements of respiratory function, selected blood and urine parameters
      including 19 metals, 17 congeners of PCDDs/Fs, 12 congeners of DL-PCBs, 30
      congeners of NDL-PCBs, 11 OH-PAHs, specific hormones (T3, T4, TSH, cortisol and
      ACTH) and common health parameters. The same protocol is applied for plant
      workers and breeders living near the plant. Individual exposure to urban
      pollution and waste incinerator fallout were assessed through the use of
      mathematical models. Information on individual habits was assessed using a
      specific questionnaire. SPoTT is the first Italian study that adopts a
      longitudinal design of appropriate statistical power to assess health impacts of
      waste incinerator plants' emission. The initial results comparing the baseline to
      the first follow-up are due at the end of 2016.

PMID- 27714599
TI  - The influence of reported ADHD and substance abuse on suicidal ideation in a non
      clinical sample of young men.
AB  - This study intended to determine whether former and current ADHD symptomatology
      is associated with suicidal ideation in a non-clinical sample of 18 year old
      males. We performed a cross sectional descriptive study of 3280 men during the
      examination for military service. The investigation included a screening for
      substance abuse, past (WURS) and current (ADHD symptom checklist) ADHD
      symptomatology and an interview about suicidal ideations. We found a correlation
      of suicidal ideations with a history of ADHD symptomatology. ADHD symptoms were
      strongly consistent over time. These results indicate that a history of
      (diagnosed or undiagnosed) ADHD could be a predictor for suicidal ideations.
      Surveying a history of ADHD in primary care might help identify subjects at risk
      for suicidal tendencies.

PMID- 27714600
TI  - [End of a psychiatric era? : Impact on the use of mechanical restraints after
      prohibition of psychiatric cage beds in a regional psychiatric department in
      Vienna, Austria].
AB  - BACKGROUND: Since June 1st, 2014 the use of cage beds, a physical coercive
      measure in psychiatric wards, is forbidden by Austrian law. The 3rd Psychiatric
      Department at the Otto Wagner Hospital in Vienna carried out a pilot-study prior
      to the application of this law and compared 6 months with and 6 months without
      the use of cage beds in psychiatric acute treatment. The investigation focused on
      the use of mechanical restraints, especially of 4-point-restraints at admission
      time. METHODS: The study collected clinical and epidemiological data from the
      patients and analyzed interviews taken with patients and staff-members after the
      use of coercive measures. RESULTS: The prohibition of cage beds was associated
      with a relative increase of the use of 4-point-restraints. Time spent in 4-point
      restraints is less than time spent in the cage beds. A trend could also be
      observed by a decrease of time spent in 4-point-restraints. Data from the
      interviews showed that there was no preference by patients of either kind of
      physical restraint. They strongly urged for more personal talks and non-physical
      and non-pharmacological therapies during admission. CONCLUSIONS: Team members
      required more human resources for the treatment of these acute psychiatric
      patients.

PMID- 27714601
TI  - Intravascular imaging comparison of two metallic limus-eluting stents abluminally
      coated with biodegradable polymers: IVUS and OCT results of the DESTINY trial.
AB  - We sought to compare, by means of IVUS and OCT imaging, the performance of a
      novel sirolimus-eluting drug-eluting stent (DES) with biodegradable polymer
      (InspironTM) to the BiomatrixTM DES. From the DESTINY trial, a total of 70
      randomized patients (2:1) were enrolled in the IVUS substudy (InspironTM, n = 46;
      BiomatrixTM: n = 20) while 25 patients were evaluated with OCT (InspironTM, n =
      19; BiomatrixTM: n = 06) at 9-month follow-up. The main endpoints were % of
      neointimal tissue obstruction (IVUS) and neointimal stut coverage (OCT) at 9
      months. Patients treated with both DES had very little NIH formation at 9 months
      either by IVUS (% of NIH obstruction of 4.9 +/- 4.1 % with InspironTM vs. 2.7 +/-
      2.9 % with BiomatrixTM, p = 0.03) or by OCT (neointimal thickness of 144.2 +/-
      72.5 um InspironTM vs. 115.0 +/- 53.9 um with BiomatrixTM, p = 0.45). Regarding
      OCT strut-level assessment, again both devices showed excellent 9-month
      performance, with high rates of strut coverage (99.49 +/- 1.01 % with InspironTM
      vs. 97.62 +/- 2.21 % with BiomatrixTM, p < 0.001) and very rare malapposition
      (0.29 +/- 1.06 % with InspironTM vs. 0.53 +/- 0.82 % with BiomatrixTM, p = 0.44).
      Patients with any uncovered struts were more frequently identified in the
      BiomatrixTM group (9.78 +/- 7.13 vs. 2.29 +/- 3.91 %, p < 0.001). In the present
      study, midterm IVUS and OCT evaluations showed that both new generation DES with
      biodegradable polymer were effective in terms of suppressing excessive neointimal
      response, with very high rates of apposed and covered struts, suggesting a
      consistent and benign healing pattern.

PMID- 27714603
TI  - Acute type A aortic dissection with mediastinal hematoma mimicking massive
      pulmonary embolus.

PMID- 27714602
TI  - Reference ranges and determinants of right ventricle outflow tract acceleration
      time in healthy adults by two-dimensional echocardiography.
AB  - The right ventricular outflow tract acceleration time (RVOT-AT) has shown to
      progressively shorten with increasing degrees of pulmonary pressure. However, the
      physiologic ranges of RVOT AT are based on small sample sizes and have not been
      investigated regarding their determining factors. The aim of this study was to
      investigate reference values and determining factors of RVOT-AT in a large
      population of healthy subjects and by values described in the literature. In the
      first part of the study, 1029 healthy subjects (mean age 45.6 +/- 16.0 years, 565
      (54.7 %) females) were prospectively assessed by clinical examination including
      demography, vital signs and echocardiography. In the second part, we performed a
      pooled analysis of eight published studies describing RVOT-AT in healthy subjects
      (n = 450). Statistical analysis included the calculation of 5 % quantiles for
      defining reference values. RVOT-AT significantly but weakly correlated with age
      (r: -0.207; p < 0.001), body mass Index (r: -0.16), systolic (r: -0.158) and
      diastolic (r: -0.137) blood pressure, heart rate (r: -0.197) and left ventricular
      (LV) E/A ratio (r: 0.229) (all p < 0.001). No differences were found with regards
      to sex. In a synopsis of both prospective and literature-based data sets, RVOT-AT
      weighted means was 138.51 ms and the 5 % quantile was 104.7 ms (95 % confidence
      interval 98.2-110.1). This study delineates the range of RVOT-AT in healthy
      adults and it's determining factors. Our study is in line with the cut-off value
      stated by the European guidelines with an RVOT-AT <=105 ms denoting abnormal
      values.

PMID- 27714604
TI  - Improving education and coping of scoliosis patients undergoing surgery, and
      their families, using e-health.
AB  - PURPOSE: Healthcare providers have limited time to spend with scoliosis patients
      who are considering surgery and their families. The purpose of this study was to
      evaluate an e-health strategy to increase knowledge and coping in patients with
      scoliosis who are surgical candidates and their families. METHODS: We enrolled
      patients with scoliosis who were candidates for surgery and their families.
      Patients and their families completed the scoliosis knowledge questionnaire,
      meaning of illness questionnaire, social support and coping questionnaires before
      and after access to a comprehensive evidence-based scoliosis website (
      http://www.aboutkidshealth.ca/scoliosis ). RESULTS: Seventy-four patients and 71
      parents completed the evaluation. While both patients and parents improved their
      knowledge of scoliosis (p = 0.001 and p = 0.003, respectively), the scores of
      patients were consistently lower than those of the parents both before and after
      website use (p = 0.0001). Only parents demonstrated a change in the meaning of
      illness questionnaire, with a small increase in the negative attitude towards
      illness and a small decrease in the positive attitude towards illness (p = 0002
      and p = 0.01, respectively). Of the 12 coping methods examined on the Adolescent
      Coping Orientation for Problem Experiences (A-COPE) instrument, patients were
      slightly more likely than parents to use relaxing and solving family problems as
      tools to cope following website access (p = 0.02 and p = 0.09, respectively).
      Parents demonstrated no significant changes in the four methods of coping on the
      Coping Health Inventory for Parents (CHIP) after website exposure. While the
      majority of patients and parents reported receiving sufficient support, over half
      of the patients indicated a need for more support in social participation.
      CONCLUSION: An evidence-based website increased the knowledge of patients and
      parents but simply providing access to the website had minimal impact on their
      coping and perceptions of social support. The website, however, provides users
      with the opportunity to absorb vital information about scoliosis across several
      media.

PMID- 27714605
TI  - Effect of left atrial volume and pulmonary vein anatomy on outcome of nMARQTM
      catheter ablation of paroxysmal atrial fibrillation.
AB  - PURPOSE: Left atrial volume (LA) and pulmonary vein (PV) anatomy may potentially
      relate to technical challenges in achieving stable and effective catheter
      position in case of atrial fibrillation (AF) ablation by means of "one-shot"
      catheters. The aim of this study was to investigate whether LA volume and PV
      anatomy, evaluated by computed tomography (CT) or magnetic resonance (MR) prior
      to ablation, predict acute and midterm outcome of AF ablation by nMARQTM.
      METHODS: We included 75 patients (mean age 58 +/- 11 years, 67 % male) with
      symptomatic paroxysmal AF. All patients underwent CT/MR scanning prior to
      catheter ablation to evaluate LA volume and PV anatomy. All the patients
      underwent PV isolation by nMARQTM, an open-irrigated mapping and radiofrequency
      (RF) decapolar ablation catheter. Ablation was guided by electroanatomic mapping
      allowing RF energy delivery in the antral region of PVs from ten irrigated
      electrodes simultaneously. RESULTS: Mean LA volume was 75 +/- 40 ml. A normal
      anatomy (4 PVs) was documented in 40 (53 %) patients and abnormal anatomy (common
      truncus or accessory PVs) in 35 patients. Mean procedural and fluoroscopy times
      were 94 +/- 55 and 8 +/- 5 min, respectively, without significant differences
      among patients with normal or abnormal anatomy (92 +/- 45 vs 95 +/- 64 min, p =
      0.85 and 6 +/- 3 vs 8 +/- 4 min, p = 0.65, respectively). Mean ablation time was
      14 +/- 3 min, and 99 % of the targeted veins were isolated with a mean of 23 +/-
      5 RF pulses per patient. After a mean follow-up of 17 +/- 8 months, 23 (31 %)
      patients had an atrial arrhythmia recurrence. Neither LA volume nor PV anatomy
      was a predictor of outcome. CONCLUSIONS: LA volume and PV anatomy did not affect
      procedural data and outcome in patients who underwent PV isolation by an open
      irrigated mapping and RF decapolar ablation catheter.

PMID- 27714607
TI  - Purification of Microbially Expressed Recombinant Proteins via a Dual ELP Split
      Intein System.
AB  - Fusions of elastin-like peptide (ELP) purification tags and self-cleaving inteins
      provide a powerful platform for purifying tagless recombinant proteins without
      the need for conventional packed-bed columns. A drawback to this method has been
      premature cleaving of the ELP tag during expression, before the purification
      procedure can take place. Here we demonstrate a split-intein method, where the
      self-cleaving intein is divided into two inactive segments during expression and
      purification. Spontaneous assembly of the purified intein segments then restores
      self-cleaving activity to deliver the tagless target protein.

PMID- 27714606
TI  - Affinity Purification of Proteins in Tag-Free Form: Split Intein-Mediated
      Ultrarapid Purification (SIRP).
AB  - Proteins purified using affinity-based chromatography often exploit a recombinant
      affinity tag. Existing methods for the removal of the extraneous tag, needed for
      many applications, suffer from poor efficiency and/or high cost. Here we describe
      a simple, efficient, and potentially low-cost approach-split intein-mediated
      ultrarapid purification (SIRP)-for both the purification of the desired tagged
      protein from Escherichia coli lysate and removal of the tag in less than 1 h. The
      N- and C-fragment of a self-cleaving variant of a naturally split DnaE intein
      from Nostoc punctiforme are genetically fused to the N-terminus of an affinity
      tag and a protein of interest (POI), respectively. The N-intein/affinity tag is
      used to functionalize an affinity resin. The high affinity between the N- and C
      fragment of DnaE intein enables the POI to be purified from the lysate via
      affinity to the resin, and the intein-mediated C-terminal cleavage reaction
      causes tagless POI to be released into the flow-through. The intein cleavage
      reaction is strongly inhibited by divalent ions (e.g., Zn2+) under non-reducing
      conditions and is significantly enhanced by reducing conditions. The POI is
      cleaved efficiently regardless of the identity of the N-terminal amino acid
      except in the cases of threonine and proline, and the N-intein-functionalized
      affinity resin can be regenerated for multiple cycles of use.

PMID- 27714608
TI  - Intracellular Production of Cyclic Peptide Libraries with SICLOPPS.
AB  - Cyclic peptides are an important class of molecules that are increasingly viewed
      as an ideal scaffold for inhibition of protein-protein interactions (PPI). Here
      we detail an approach that enables the intracellular synthesis of cyclic peptide
      libraries of around 108 members. The method utilizes split intein mediated
      circular ligation of peptides and proteins (SICLOPPS), taking advantage of split
      intein splicing to cyclize a library of peptide sequences. SICLOPPS allows the
      ring size, set residues and number of random residues within a library to be
      predetermined by the user. SICLOPPS libraries have been combined with a variety
      of cell-based screens to identify cyclic peptide inhibitors of a variety of
      enzymes and protein-protein interactions.

PMID- 27714609
TI  - Recombinant Expression of Cyclotides Using Split Inteins.
AB  - Cyclotides are fascinating microproteins (~30 residues long) present in several
      families of plants that share a unique head-to-tail circular knotted topology of
      three disulfide bridges, with one disulfide penetrating through a macrocycle
      formed by the two other disulfides and inter-connecting peptide backbones,
      forming what is called a cystine knot topology. Naturally occurring cyclotides
      have shown to posses various pharmacologically relevant activities and have been
      reported to cross cell membranes. Altogether, these features make the cyclotide
      scaffold an excellent molecular framework for the design of novel peptide-based
      therapeutics, making them ideal substrates for molecular grafting of biological
      peptide epitopes. In this chapter we describe how to express a native folded
      cyclotide using intein-mediated protein trans-splicing in live Escherichia coli
      cells.

PMID- 27714610
TI  - Ribosomal Synthesis of Thioether-Bridged Bicyclic Peptides.
AB  - Many biologically active peptides found in nature exhibit a bicyclic structure
      wherein a head-to-tail cyclic backbone is further constrained by an
      intramolecular linkage connecting two side chains of the peptide. Accordingly,
      methods to access macrocyclic peptides sharing this overall topology could be of
      significant value toward the discovery of new functional entities and bioactive
      compounds. With this goal in mind, we recently developed a strategy for enabling
      the biosynthesis of thioether-bridged bicyclic peptides in living bacterial
      cells. This method involves a split intein-catalyzed head-to-tail cyclization of
      a ribosomally produced precursor peptide, combined with inter-sidechain cross
      linking through a genetically encoded cysteine-reactive amino acid. This approach
      can be applied to direct the formation of structurally diverse bicyclic peptides
      with high efficiency and selectivity in living Escherichia coli cells and
      provides a platform for the generation of combinatorial libraries of genetically
      encoded bicyclic peptides for screening purposes.

PMID- 27714611
TI  - Preparation of Semisynthetic Peptides Macrocycles Using Split Inteins.
AB  - Cyclic peptides are highly desired molecules not only for basic research but also
      for many biomedical and pharmacological applications. Due to their potentially
      superior physicochemical properties as compared to their linear counterparts,
      they are considered as ideal candidates for studying protein-protein
      interactions, among others. Most of the methods developed in recent years to
      prepare cyclic peptides focus either on a synthetic or a recombinant route. While
      the former provides access to diversified, noncanonical peptides, including
      unnatural and D-amino acid, for example, the latter can harness the power of
      genetic randomization to generate and select from large peptide libraries. Only
      few approaches have been reported to prepare semisynthetic macrocycles that would
      benefit from both the advantages associated with synthetic and genetically
      encoded parts. We describe in this chapter a chemo-enzymatic method to make
      semisynthetic cyclic peptides in vitro from two fragments using protein trans
      splicing and bioorthogonal oxime ligation.

PMID- 27714612
TI  - Semisynthesis of Membrane-Attached Proteins Using Split Inteins.
AB  - The site-selective installation of lipid modifications on proteins is critically
      important in our understanding of how membrane association influences the
      biophysical properties of proteins as well as to study certain proteins in their
      native environment. Here, we describe the use of split inteins for the C-terminal
      attachment of lipid-modified peptides to virtually any protein of interest (POI)
      via protein trans-splicing (PTS). To achieve this, the protein of interest is
      expressed in fusion with the N-terminal split intein segment and the C-terminal
      split intein segment is prepared by solid phase peptide synthesis. A synthetic
      peptide carrying two lipid chains is also made chemically to serve as a membrane
      anchor and subsequently linked to the C-terminal split intein by native chemical
      ligation. Proteins of interest for our work are the prion protein as well as
      small GTPases; however, extensions to other POIs are possible. Detailed
      information for the C-terminal introduction of a lipidated membrane anchor (MA)
      peptide using split intein systems from Synechocystis spp. and Nostoc punctiforme
      for the Prion protein (PrP, as a challenging protein of interest) and the
      enhanced green-fluorescent protein (eGFP, as an easily trackable target protein)
      are provided here.

PMID- 27714613
TI  - Protein Chemical Modification Inside Living Cells Using Split Inteins.
AB  - Methods to visualize, track, measure, and perturb or activate proteins in living
      cells are central to biomedical efforts to characterize and understand the
      spatial and temporal underpinnings of life inside cells. Although fluorescent
      proteins have proven to be extremely useful for in vivo studies of protein
      function, their utility is inherently limited because their spectral and
      structural characteristics are interdependent. These limitations have spurred the
      creation of alternative approaches for the chemical labeling of proteins. We
      describe in this protocol the use of fluorescence resonance emission transfer
      (FRET)-quenched DnaE split-inteins for the site-specific labeling and concomitant
      fluorescence activation of proteins in living cells. We have successfully
      employed this approach for the site-specific in-cell labeling of the DNA binding
      domain (DBD) of the transcription factor YY1 using several human cell lines.
      Moreover, we have shown that this approach can be also used for modifying
      proteins in order to control their cellular localization and potentially alter
      their biological activity.

PMID- 27714614
TI  - Segmental Isotopic Labeling of Proteins for NMR Study Using Intein Technology.
AB  - Segmental isotopic labeling of samples for NMR studies is attractive for large
      complex biomacromolecular systems, especially for studies of function-related
      protein-ligand interactions and protein dynamics (Goto and Kay, Curr Opin Struct
      Biol 10:585-592, 2000; Rosa et al., Molecules (Basel, Switzerland) 18:440, 2013;
      Hiroaki, Expert Opin Drug Discovery 8:523-536, 2013). Advantages of segmental
      isotopic labeling include selective examination of specific segment(s) within a
      protein by NMR, significantly reducing the spectral complexity for large
      proteins, and allowing for the application of a variety of solution-based NMR
      strategies. By utilizing intein techniques (Wood and Camarero, J Biol Chem
      289:14512-14519, 2014; Paulus, Annu Rev Biochem 69:447-496, 2000), two related
      approaches can generally be used in the segmental isotopic labeling of proteins:
      expressed protein ligation (Muir, Annu Rev Biochem 72:249-289, 2003) and protein
      trans-splicing (Shah et al., J Am Chem Soc 134:11338-11341, 2012). Here, we
      describe general implementation and latest improvements of expressed protein
      ligation method for the production of segmental isotopic labeled NMR samples.

PMID- 27714615
TI  - Segmental Isotope Labeling of Insoluble Proteins for Solid-State NMR by Protein
      Trans-Splicing.
AB  - Solid-state NMR spectroscopy (ssNMR) is uniquely suited for atomic-resolution
      structural investigations of large protein assemblies, which are notoriously
      difficult to study due to their insoluble and non-crystalline nature. However,
      assignment ambiguities because of limited resolution and spectral crowding are
      currently major hurdles that quickly increase with the length of the polypeptide
      chain. The line widths of ssNMR signals are independent of proteins size, making
      segmental isotope labeling a powerful approach to overcome this limitation. It
      allows a scalable reduction of signal overlap, aids the assignment of repetitive
      amino acid sequences, and can be easily combined with other selective isotope
      labeling strategies. Here we present a detailed protocol for segmental isotope
      labeling of insoluble proteins using protein trans-splicing. Our protocol
      exploits the ability of many insoluble proteins, such as amyloid fibrils, to fold
      correctly under in vitro conditions. In combination with the robust trans
      splicing efficiency of the intein DnaE from Nostoc punctiforme, this allows for
      high yields of segmentally labeled protein required for ssNMR analysis.

PMID- 27714616
TI  - Split-Intein Triggered Protein Hydrogels.
AB  - Proteins are nature's building blocks and indispensable in living organisms.
      Protein-based hydrogels have a wide variety of applications in research and
      biotechnology. In this chapter, we describe an intein-mediated protein hydrogel
      that utilizes two synthetic soluble protein block copolymers, each containing a
      subunit of a trimeric protein that serves as a cross-linker and one half of the
      naturally split DnaE intein from Nostoc punctiforme. Mixing of these two protein
      block copolymers initiates an intein trans-splicing reaction that constitutes a
      self-assembling polypeptide flanked by cross-linkers, triggering protein hydrogel
      formation. The generated hydrogels are highly stable under both acidic and basic
      conditions, and at temperatures up to 50  degrees C. In addition, these hydrogels
      are able to undergo rapid reassembly after shear-induced rupture. Incorporation
      of an appropriate binding motif into the protein block copolymers enables the
      convenient site-specific incorporation of functional globular proteins into the
      hydrogel network.

PMID- 27714617
TI  - A Recessive Pollination Control System for Wheat Based on Intein-Mediated Protein
      Splicing.
AB  - A transgene-expression system for wheat that relies on the complementation of
      inactive precursor protein fragments through a split-intein system is described.
      The N- and C-terminal fragments of a barnase gene from Bacillus amyloliquifaciens
      were fused to intein sequences from Synechocystis sp. and transformed into wheat
      plants. Upon translation, both barnase fragments are assembled by an
      autocatalytic intein-mediated trans-splicing reaction, thus forming a cytotoxic
      enzyme. This chapter focuses on the use of introns and flexible polypeptide
      linkers to foster the expression of a split-barnase expression system in plants.
      The methods and protocols that were employed with the objective to test the
      effects of such genetic elements on transgene expression and to find the optimal
      design of expression vectors for use in wheat are provided. Split-inteins can be
      used to form an agriculturally important trait (male sterility) in wheat plants.
      The use of this principle for the production of hybrid wheat seed is described.
      The suggested toolbox will hopefully be a valuable contribution to future
      optimization strategies in this commercially important crop.

PMID- 27714618
TI  - Conditional Toxin Splicing Using a Split Intein System.
AB  - Protein toxin splicing mediated by split inteins can be used as a strategy for
      conditional cell ablation. The approach requires artificial fragmentation of a
      potent protein toxin and tethering each toxin fragment to a split intein
      fragment. The toxin-intein fragments are, in turn, fused to dimerization domains,
      such that addition of a dimerizing agent reconstitutes the split intein. These
      chimeric toxin-intein fusions remain nontoxic until the dimerizer is added,
      resulting in activation of intein splicing and ligation of toxin fragments to
      form an active toxin. Considerations for the engineering and implementation of
      conditional toxin splicing (CTS) systems include: choice of toxin split site,
      split site (extein) chemistry, and temperature sensitivity. The following method
      outlines design criteria and implementation notes for CTS using a previously
      engineered system for splicing a toxin called sarcin, as well as for developing
      alternative CTS systems.

PMID- 27714619
TI  - Photocontrol of the Src Kinase in Mammalian Cells with a Photocaged Intein.
AB  - Recently developed methods that can photochemically control protein activities
      and functions in live cells have opened up new opportunities for studying
      signaling networks at the cellular and subcellular levels. Our laboratory has
      reported a genetically encoded photoactivatable intein, which allows the direct
      photocontrol of primary sequences of proteins, and consequently, their activities
      and functions in live mammalian cells. Herein, we provide details on experimental
      design and the utilization of this photocaged intein to photoactivate the Src
      tyrosine kinase in human embryonic kidney (HEK) 293T cells. The described
      procedures may be adopted to photocontrol other proteins in other types of
      mammalian cells.

PMID- 27714620
TI  - LOV2-Controlled Photoactivation of Protein Trans-Splicing.
AB  - Protein trans-splicing is a posttranslational modification that joins two protein
      fragments together via a peptide a bond in a process that does not require
      exogenous cofactors. Towards achieving cellular control, synthetically engineered
      systems have used a variety of stimuli such as small molecules and light.
      Recently, split inteins have been engineered to be photoactive by the LOV2 domain
      (named LOVInC). Herein, we discuss (1) designing of LOV2-activated target
      proteins (e.g., inteins), (2) selecting feasible splice sites for the extein, and
      (3) imaging cells that express LOVInC-based target exteins.

PMID- 27714621
TI  - A Cassette Approach for the Identification of Intein Insertion Sites.
AB  - Over the past decade split inteins have established themselves as powerful tools
      for protein engineering, protein semisynthesis, and protein functional control
      approaches. Their key advantage lies in the protein trans-splicing (PTS) reaction
      that enables posttranslational protein assembly from two independent, even
      synthetic, peptide precursors. However, since most split intein applications deal
      with fragmentation and modification of proteins, various issues can arise,
      ranging from reduced stability to impairment of protein folding. In this chapter
      I address how the usage of DNA encoded intein cassettes can streamline and speed
      up the identification of functional split intein insertion sites in novel
      proteins of interest (POI).

PMID- 27714622
TI  - Computational Prediction of New Intein Split Sites.
AB  - Split inteins have emerged as a powerful tool in protein engineering. We describe
      a reliable in silico method to predict viable split sites for the design of new
      split inteins. A computational circular permutation (CP) prediction method
      facilitates the search for internal permissive sites to create artificial
      circular permutants. In this procedure, the original amino- and carboxyl-termini
      are connected and new termini are created. The identified new terminal sites are
      promising candidates for the generation of new split sites with the backbone
      opening being tolerated by the structural scaffold. Here we show how to integrate
      the online usage of the CP predictor, CPred, in the search of new split intein
      sites.

PMID- 27714623
TI  - CORR Insights(r): Are Biopsy Tracts a Concern for Seeding and Local Recurrence in
      Sarcomas?

PMID- 27714624
TI  - CORR Insights(r): Operative Fluoroscopic Correction Is Reliable and Correlates
      With Postoperative Radiographic Correction in Periacetabular Osteotomy.

PMID- 27714626
TI  - Seymour "Sy" Meyerson, December 4, 1916-May 28, 2016.

PMID- 27714625
TI  - Drug utilization study of systemic antifungal agents in a Brazilian tertiary care
      hospital.
AB  - Background The inappropriate use of systemic antifungal agents can result in
      unnecessary exposure, adverse events, increased microbial resistance and
      increased costs. Aim This study analysed the use of systemic antifungal agents
      and adherence to treatment guidelines for fungal infections. Setting A Brazilian
      tertiary hospital. Methods This cross-sectional study investigated 183 patients
      who were treated with systemic antifungals. Antifungal drugs were classified
      according to the fourth level of the Anatomical Therapeutic Chemical
      classification system. The appropriateness of treatments was analysed with
      respect to the indication, dose and potential drug-drug interactions. Descriptive
      and univariate statistical analyses were performed. The main outcome measure was
      the frequency of adherence to treatment guidelines for fungal infections. Results
      The number of established treatments was 320, with 163 (50.9 %) pre-emptive, 63
      (19.7 %) targeted, 56 (17.5 %) empirical and 38 (11.9 %) prophylactic treatments.
      The overall adherence to the treatment guidelines was 29.4 %. The proportion of
      appropriate treatment considering indication, dosage and drug-drug interactions
      was 84.1, 67.8 and 47.2 %, respectively. The most commonly prescribed systemic
      antifungal agents were fluconazole in 170 (53.1 %), voriconazole in 43 (13.4 %)
      and amphotericin B deoxycholate in 36 (11.3 %) cases. Conclusion The study showed
      a low proportion of appropriate antifungal drug use; the dosage and drug-drug
      interactions criteria were the determining factors for the high percentage of non
      adherence to treatment guidelines in the hospital. The profile of antifungal
      agents used showed the predominance of fluconazole as well as the use of new
      antifungal drugs.

PMID- 27714627
TI  - Non-graduation after comprehensive school, and early retirement but not
      unemployment are prominent in childhood cancer survivors-a Finnish registry-based
      study.
AB  - BACKGROUND: In order to assess neurocognitive and social outcomes after childhood
      cancer, we explored the educational and vocational attainments of Finnish
      survivors in comparison to matched population controls. METHODS: From national
      registries, we identified survivors (n = 3243) born from 1960 to 1992 and aged
      below 16 at cancer diagnosis (years 1964-2009) as well as their controls (n =
      16,215). Data on educational achievements, yearly income, employment status, and
      retirement were retrieved from Statistics Finland. RESULTS: The median (range)
      age at study was 28 (17-50) years. The proportion of those with no education
      after comprehensive school was higher than controls for all the diagnostic
      groups: brain tumor (BT) (33.5 vs 23.0 %), solid tumor (ST) (25.0 vs 21.4 %), and
      leukemia/NHL (29.2 vs 23.1 %). Odds ratios (OR) for unemployment were not
      significantly elevated in any survivor group compared to controls, but OR for
      being retired was elevated in each survivor group (BT 14.8, ST 2.2, leukemia/NHL
      4.0). Irradiation significantly increased that OR only in BT survivors.
      Leukemia/NHL survivors treated after 1992 had lower risk for early retirement (OR
      0.6) compared to those diagnosed earlier. CONCLUSIONS: Survivors had higher
      frequencies than controls for lacking further education after comprehensive
      school. Unemployment was not common, but risk for early retirement was
      significantly increased in each three survivor group. IMPLICATIONS FOR CANCER
      SURVIVORS: Reassuring is that premature retirement was less common during the
      most recent treatment era. Screening and follow-up of psychosocial performance
      more effectively might be essential, and there is a need for studies on
      possibility for effective rehabilitation of the survivors.

PMID- 27714628
TI  - Ebola virus and arthropods: a literature review and entomological consideration
      on the vector role.
AB  - Ebola virus is a pathogen responsible for a severe disease that affects humans
      and several animal species. To date, the natural reservoir of this virus is not
      known with certainty, although it is believed that fruit bats (Chiroptera:
      Pteropodidae) play an important role in maintaining the virus in nature. Although
      information on viral transmission from animals to humans is not clear, the role
      of arthropods has come under suspicion. In this article, we review the potential
      role of arthropods in spreading Ebola virus, acting as mechanical or biological
      vectors.

PMID- 27714629
TI  - Discriminative Stimulus Effects of Abused Inhalants.
AB  - Inhalants are a loosely organized category of abused compounds defined entirely
      by their common route of administration. Inhalants include volatile solvents,
      fuels, volatile anesthetics, gasses, and liquefied refrigerants, among others.
      They are ubiquitous in modern society as ingredients in a wide variety of
      household, commercial, and medical products. Persons of all ages abuse inhalants
      but the highest prevalence of abuse is in younger adolescents. Although inhalants
      have been shown to act upon a host of neurotransmitter receptors, the stimulus
      effects of the few inhalants which have been trained or tested in drug
      discrimination procedures suggest that their discriminative stimulus properties
      are mediated by a few key neurotransmitter receptor systems. Abused volatile
      solvent inhalants have stimulus effects that are similar to a select group of
      GABAA positive modulators comprised of benzodiazepines and barbiturates. In
      contrast the stimulus effects of nitrous oxide gas appear to be at least
      partially mediated by uncompetitive antagonism of NMDA receptors. Finally,
      volatile anesthetic inhalants have stimulus effects in common with both GABAA
      positive modulators as well as competitive NMDA antagonists. In addition to a
      review of the pharmacology underlying the stimulus effects of inhalants, the
      chapter also discusses the scientific value of utilizing drug discrimination as a
      means of functionally grouping inhalants according to their abuse-related
      pharmacological properties.

PMID- 27714630
TI  - Low-Intensity Ultrasound Decreases alpha-Synuclein Aggregation via Attenuation of
      Mitochondrial Reactive Oxygen Species in MPP(+)-Treated PC12 Cells.
AB  - Many studies have shown that mitochondrial dysfunction and the subsequent
      oxidative stress caused by excessive reactive oxygen species (ROS) generation
      play a central role in the pathogenesis of Parkinson's disease (PD). We have
      previously shown that low-intensity ultrasound (LIUS) could reduce ROS generation
      by L-buthionine-(S,R)-sulfoximine (BSO) in retinal pigment epithelial cells. In
      this study, we studied the effects of LIUS stimulation on the ROS-dependent alpha
      synuclein aggregation in 1-methyl-4-phenylpyridinium ion (MPP+)-treated PC12
      cells. We found that LIUS stimulation suppressed the MPP+-induced ROS generation
      and inhibition of mitochondrial complex I activity in PC12 cells in an intensity
      dependent manner at 30, 50, and 100 mW/cm2. Furthermore, LIUS stimulation at 100
      mW/cm2 suppressed inhibition of mitochondrial complex activity by MPP+ and
      actually resulted in a decrease of alpha-synuclein phosphorylation and
      aggregation induced by MMP+ treatment in PC12 cells. LIUS stimulation also
      inhibited expression of casein kinase 2 (CK2) that appears to mediate ROS
      dependent alpha-synuclein aggregation. Finally, LIUS stimulation alleviated the
      death of PC12 cells by MPP+ treatment in an intensity-dependent manner. We,
      hence, suggest that LIUS stimulation inhibits ROS generation by MPP+ treatment,
      thereby suppressing alpha-synuclein aggregation in PC12 cells.

PMID- 27714631
TI  - Creatine Prevents Corticosterone-Induced Reduction in Hippocampal Proliferation
      and Differentiation: Possible Implication for Its Antidepressant Effect.
AB  - The benefits of creatine supplementation have been reported in a broad range of
      central nervous system diseases, including depression, although the mechanisms
      underlying these effects remain to be understood. In the present study, we
      investigated the ability of creatine to counteract the morphological and
      behavioral effects elicited by chronic administration of corticosterone (CORT, 20
      mg/kg, p.o.) for 21 days to mice, a pharmacological model of depression that
      mimics exposure to stress. CORT treatment increased immobility time in the tail
      suspension test (TST) and forced swim test (FST), as well as latency to
      immobility in the FST, and decreased the sucrose consumption in the sucrose
      preference test (SPT). These behavioral effects were associated with decreased
      hippocampal cell proliferation and neuronal differentiation and increased glial
      fibrillary acid protein (GFAP) immunostaining (suggestive of astrogliosis) in
      dentate gyrus (DG) of the hippocampus. These CORT-induced alterations were
      abolished by treatment with either fluoxetine (a conventional antidepressant) or
      creatine for 21 days (both 10 mg/kg, p.o.). In addition, fluoxetine, but not
      creatine, was able to reverse the CORT-induced reduction in serum CORT levels.
      Collectively, our results suggest that creatine produces morphological
      alterations that contribute to the improvement of depressive-like behaviors
      triggered by chronic CORT administration in mice.

PMID- 27714632
TI  - Semaphorin 7A as a Potential Therapeutic Target for Multiple Sclerosis.
AB  - Semaphorin 7A (sema7A) is classified as an immune semaphorin with dual functions
      in the immune system and in the central nervous system (CNS). These molecules are
      of interest due to their potential role in multiple sclerosis (MS), which is a
      chronic demyelinating and neurodegenerative disease of autoimmune origin. In this
      study, we elucidated the role of sema7A in neuroinflammation using both in vitro
      and in vivo experimental models. In an in vitro model of neuroinflammation, using
      cerebellar organotypic slice cultures, we observed that challenge with
      lipopolysaccharide (LPS) endotoxin did not affect demyelination or cell death in
      sema7A-deficient cultures compared to wild-type cultures. Moreover, the in vivo
      outcome of experimental autoimmune encephalomyelitis (EAE) in sema7A-deficient
      mice was altered in an antigen- and adjuvant-dose-dependent manner, while no
      differences were observed in the wild-type counterparts. Altogether, these
      results indicate that sema7A is involved in peripheral immunity and CNS
      inflammation in MS pathogenesis. Indeed, these data suggest that sema7A might be
      a potential therapeutic target to treat MS and autoimmune conditions.

PMID- 27714633
TI  - Hypoxic and Reoxygenated Microenvironment: Stemness and Differentiation State in
      Glioblastoma.
AB  - Glioblastoma (GBM) is the most common and aggressive primary malignant brain
      tumor in adults. Hypoxia is a distinct feature in GBM and plays a significant
      role in tumor progression, resistance to treatment, and poor outcome. However,
      there is lack of studies relating type of cell death, status of Akt
      phosphorylation on Ser473, mitochondrial membrane potential, and morphological
      changes of tumor cells after hypoxia and reoxygenation. The rat glioma C6 cell
      line was exposed to oxygen deprivation (OD) in 5 % fetal bovine serum (FBS) or
      serum-free media followed by reoxygenation (RO). OD induced apoptosis on both 5 %
      FBS and serum-free groups. Overall, cells on serum-free media showed more
      profound morphological changes than cells on 5 % FBS. Moreover, our results
      suggest that OD combined with absence of serum provided a favorable environment
      for glioblastoma dedifferentiation to cancer stem cells, since nestin, and CD133
      levels increased. Reoxygenation is present in hypoxic tumors through microvessel
      formation and cell migration to oxygenated areas. However, few studies approach
      these phenomena when analyzing hypoxia. We show that RO caused morphological
      alterations characteristic of cells undergoing a differentiation process due to
      increased GFAP. In the present study, we characterized an in vitro hypoxic
      microenvironment associated with GBM tumors, therefore contributing with new
      insights for the development of therapeutics for resistant glioblastoma.

PMID- 27714634
TI  - Zinc Oxide Nanoparticle Induces Microglial Death by NADPH-Oxidase-Independent
      Reactive Oxygen Species as well as Energy Depletion.
AB  - Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered
      nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through
      various routes, interact with different brain cells, and alter their activity.
      Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle
      exposure can activate microglia and induce neuroinflammation. Simultaneous to
      activation, microglial death can exacerbate the scenario. Therefore, we focused
      on studying the effect of ZnO-NP on microglia and finding out the pathway
      involved in the microglial death. The present study showed that the 24 h
      inhibitory concentration 50 (IC50) of ZnO-NP for microglia is 6.6 MUg/ml. Early
      events following ZnO-NP exposure involved increase in intracellular calcium level
      as well as reactive oxygen species (ROS). Neither of NADPH oxidase inhibitors,
      apocynin, (APO) and diphenyleneiodonium chloride (DPIC) were able to reduce the
      ROS level and rescue microglia from ZnO-NP toxicity. In contrary, N-acetyl
      cysteine (NAC) showed opposite effect. Exogenous supplementation of superoxide
      dismutase (SOD) reduced ROS significantly even beyond control level but partially
      rescued microglial viability. Interestingly, pyruvate supplementation rescued
      microglia near to control level. Following 10 h of ZnO-NP exposure, intracellular
      ATP level was measured to be almost 50 % to the control. ZnO-NP-induced ROS as
      well as ATP depletion both disturbed mitochondrial membrane potential and
      subsequently triggered the apoptotic pathway. The level of apoptosis-inducing
      proteins was measured by western blot analysis and found to be upregulated. Taken
      together, we have deciphered that ZnO-NP induced microglial apoptosis by NADPH
      oxidase-independent ROS as well as ATP depletion.

PMID- 27714636
TI  - MARK2/Par1b Insufficiency Attenuates DVL Gene Transcription via Histone
      Deacetylation in Lumbosacral Spina Bifida.
AB  - Dishevelled (DVL/Dvl) genes play roles in canonical and noncanonical Wnt
      signaling, both of which are essential in neural tube closing and are involved in
      balancing neural progenitor growth and differentiation, or neuroepithelial cell
      polarity, respectively. In mouse Dvl haploinsufficiency leads to neural tube
      defects (NTDs), which represent the second most common birth defects. However,
      DVL genes' genetic contributions in human NTDs are modest. We sought to explore
      the molecular impact on such genes in human NTDs in a Han Chinese cohort. In 47
      cases with NTDs and 61 matched controls, in brain tissues, the DVL1/2 mRNA levels
      were correlated with the levels of a serine/threonine protein kinase MARK2, and
      in 20 cases with lumbosacral spina bifida, the mRNA levels of DVL1 and MARK2 were
      significantly decreased; by contrast, only an intronic rare variant was found.
      Moreover, in an extended population, we found merely three novel rare missense
      variants in 1 % of individuals with NTDs. In cell-based assays, Mark2 depletion
      indeed reduces Dvl gene expression and interrupts neural stem cell (NSCs) growth
      and differentiation, which are likely to be mediated through a decrease in class
      IIa HDAC phosphorylation and reduced H3K4ac and H3K27ac occupancies at the Dvl1/2
      promoters. Finally, the detections of folate concentration in human brain tissue
      and NSCs and MEF cells indicates that folate deficiency contributes to the
      observed decreases in Mark2 and Dvl1 expression. Our present study raises a
      potential common pathogenicity mechanism in human lumbosacral spina bifida about
      DVL genes rather than their genetic pathogenic role.

PMID- 27714638
TI  - Characterization of Four New Distinct omega-Transaminases from Pseudomonas putida
      NBRC 14164 for Kinetic Resolution of Racemic Amines and Amino Alcohols.
AB  - Four uncharacterized omega-transaminases (omegaTAs) from Pseudomonas putida NBRC
      14164 have been identified and cloned from the pool of fully sequenced genomes.
      The genes were functionally expressed in Escherichia coli BL21, and the enzymes
      were purified and characterized. Four TAs showed highly (S)-selective omegaTA
      activity and converted (S)-alpha-methylbenzylamine and pyruvate to acetophenone
      and L-Ala. The maximum activity of cloned enzymes was in the pH range of 8.0-8.5
      (Pp36420), 8.5-9.5 (Pp21050), 9.0-9.5 (PpspuC), and 9.5-10.5 (PpbauA), and the
      optimal temperatures were at 35  degrees C (Pp36420, Pp21050, and PpspuC) and 50 
      degrees C (PpbauA), respectively, with K M of 161.3 mM (Pp21050), 136.7 mM
      (PpbauA), 398.5 mM (Pp36420), and 130.9 mM (PpspuC) and yielding a catalytic
      efficiency k cat/K M of 0.015, 0.003, 0.012, and 0.023 mM-1 s-1. Several racemic
      amines and amino alcohols were resolved by the cloned omegaTAs; perfect
      conversions (48-50 %) were obtained by at least one enzyme, and the residual
      substrates were left with 97-99 % ee. Kinetic resolution of racemic
      phenylglycinol was done with PpspuC in a 100-mL scale. Enaniomeric excess of (S)
      phenylglycinol reached 99 % with 45 % isolated yield. The high enantioselectivity
      and large substrate spectra of the cloned PpTAs showed an attractive potency for
      biotechnology application in production of chiral amines and amino alcohols.

PMID- 27714637
TI  - Headaches: a Review of the Role of Dietary Factors.
AB  - Dietary triggers are commonly reported by patients with a variety of headaches,
      particularly those with migraines. The presence of any specific dietary trigger
      in migraine patients varies from 10 to 64 % depending on study population and
      methodology. Some foods trigger headache within an hour while others develop
      within 12 h post ingestion. Alcohol (especially red wine and beer), chocolate,
      caffeine, dairy products such as aged cheese, food preservatives with nitrates
      and nitrites, monosodium glutamate (MSG), and artificial sweeteners such as
      aspartame have all been studied as migraine triggers in the past. This review
      focuses the evidence linking these compounds to headache and examines the
      prevalence of these triggers from prior population-based studies. Recent
      literature surrounding headache related to fasting and weight loss as well as
      elimination diets based on serum food antibody testing will also be summarized to
      help physicians recommend low-risk, non-pharmacological adjunctive therapies for
      patients with debilitating headaches.

PMID- 27714635
TI  - Mitochondria-Associated Membranes (MAMs): Overview and Its Role in Parkinson's
      Disease.
AB  - Mitochondria-associated membranes (MAMs) are structures that regulate
      physiological functions between endoplasmic reticulum (ER) and mitochondria in
      order to maintain calcium signaling and mitochondrial biogenesis. Several
      proteins located in MAMs, including those encoded by PARK genes and some of
      neurodegeneration-related proteins (huntingtin, presenilin, etc.), ensure this
      regulation. In this regard, MAM alteration is associated with neurodegenerative
      diseases such as Parkinson's (PD), Alzheimer's (AD), and Huntington's diseases
      (HD) and contributes to the appearance of the pathogenesis features, i.e.,
      autophagy dysregulation, mitochondrial dysfunction, oxidative stress, and lately,
      neuronal death. Moreover,, ER stress and/or damaged mitochondria can be the cause
      of these disruptions. Therefore, ER-mitochondria contact structure and function
      are crucial to multiple cellular processes. This review is focused on the
      molecular interaction between ER and mitochondria indispensable to MAM formation
      and on MAM alteration-induced etiology of neurodegenerative diseases.

PMID- 27714640
TI  - Cloning and Characterization of Cold-Adapted alpha-Amylase from Antarctic
      Arthrobacter agilis.
AB  - In this study, the gene encoding an alpha-amylase from a psychrophilic
      Arthrobacter agilis PAMC 27388 strain was cloned into a pET-28a(+) vector and
      heterologously expressed in Escherichia coli BL21(DE3). The recombinant alpha
      amylase with a molecular mass of about 80 kDa was purified by using Ni2+-NTA
      affinity chromatography. This recombinant alpha-amylase exhibited optimal
      activity at pH 3.0 and 30  degrees C and was highly stable at varying
      temperatures (30-60  degrees C) and within the pH range of 4.0-8.0. Furthermore,
      alpha-amylase activity was enhanced in the presence of FeCl3 (1 mM) and beta
      mercaptoethanol (5 mM), while CoCl2 (1 mM), ammonium persulfate (5 mM), SDS (10
      %), Triton X-100 (10 %), and urea (1 %) inhibited the enzymatic activity.
      Importantly, the presence of Ca2+ ions and phenylmethylsulfonyl fluoride (PMSF)
      did not affect enzymatic activity. Thin layer chromatography (TLC) analysis
      showed that recombinant A. agilis alpha-amylase hydrolyzed starch, maltotetraose,
      and maltotriose, producing maltose as the major end product. These results make
      recombinant A. agilis alpha-amylase an attractive potential candidate for
      industrial applications in the textile, paper, detergent, and pharmaceutical
      industries.

PMID- 27714639
TI  - Caralluma umbellata Peroxidase: Biochemical Characterization and Its
      Detoxification Potentials in Comparison with Horseradish Peroxidase.
AB  - Caralluma umbellata peroxidase (CUP) is an acidic heme-containing protein having
      a molecular weight of ~42 kDa and is specific to guaiacol. It is not a
      glycoprotein. It was purified to 12.5-fold purity with 6.16 % yield. Its activity
      is dependent on hydrogen peroxide and has an optimum pH and temperature of 6.2
      and 45  degrees C respectively. It can decolorize dyes, viz., Aniline Blue,
      Reactive Black 5, and Reactive Blue 19 but not Congo Red, while HRP can
      decolorize Congo Red also. It has lignin-degrading potentiality as it can
      decompose veratryl alcohol. Detoxification of phenol was more by CUP compared to
      HRP while with p-nitrophenol HRP has a greater detoxification rate. Based on our
      results, CUP was identified to be capable of oxidizing a variety of hazardous
      substances and also a lignin-degrading plant biocatalyst.

PMID- 27714641
TI  - Economic Growth, Climate Change, and Obesity.
AB  - Human and planetary health as well as economic growth are firmly interlinked and
      subject to complex interaction effects. In this paper, we provide an overview of
      interlinkages between economic growth, climate change, and obesity focusing on
      recent advances in the literature. In addition to empirical findings, we discuss
      different theoretical frameworks used to conceptualize these complex links and
      highlight policy options and challenges. We conclude that policies addressing
      both climate change and obesity simultaneously are particularly promising and
      often suitable for ensuring sustainable development.

PMID- 27714642
TI  - Role of New Antiplatelet Drugs on Cardiovascular Disease: Update on Cangrelor.
AB  - Dual therapy with a P2Y12 receptor antagonist in addition to aspirin is the
      antiplatelet treatment of choice in patients with acute coronary syndromes or
      undergoing percutaneous coronary intervention (PCI). However, available oral
      P2Y12 antagonists have several limitations, mostly due to their pharmacological
      profile, which can affect outcomes in certain clinical settings. Cangrelor is an
      intravenous, direct-acting, potent P2Y12 inhibitor with rapid onset and offset of
      action, which has been recently approved for clinical use in patients undergoing
      PCI. In clinical trials, cangrelor has demonstrated greater efficacy than
      clopidogrel with a favorable safety profile among PCI patients not receiving
      pretreatment with oral P2Y12 antagonists. However, its definitive role in
      contemporary practice is yet to be determined. This review aims to provide a
      comprehensive overview of the current status of knowledge on cangrelor, focusing
      on its pharmacological properties, clinical development, and the potential
      applications of this newly available agent.

PMID- 27714643
TI  - Transarterial Chemoembolization for the Treatment of Advanced-Stage
      Hepatocellular Carcinoma.
AB  - It remains controversial whether transarterial chemoembolization (TACE) should be
      performed in patients with advanced-stage hepatocellular carcinoma (HCC). The
      present large retrospective cohort study aimed to define the survival outcome
      following TACE of advanced HCC and to identify the prognostic factors. Five
      hundred eight patients with Barcelona Clinic Liver Cancer (BCLC) C-stage HCC,
      Child-Pugh A/B who were treated with TACE between November 1998 and December 2013
      were identified. There was no significant difference in overall survival (OS)
      between patients with Eastern Cooperative Oncology Group (ECOG) 0 and those with
      ECOG >=1 (10.5 months vs. 11.9 months, P = 0.87). The median OS of patients
      without portal vein tumor thrombosis (PVTT) was longer than that of patients with
      PVTT (16.9 vs. 6.1 months, P < 0.001). Child-Pugh B class, PVTT, extrahepatic
      metastasis, tumor size >=5 cm, number of tumors >=3, and alpha-fetoprotein >=400
      ng/dL were significantly associated with decreased survival and were used for
      determining the risk scores. All patients were divided into two groups (low-risk
      and high-risk groups) according to the cutoff value of 6.5 for risk scores. The
      patients with a value <6.5 (low-risk group) had significantly longer survival
      than those with >6.5 (high-risk group) (24.1 vs. 7.5 months, respectively; P <
      0.001). TACE is an effective therapy for select patients with advanced stage HCC
      and may provide equal or improved survival as compared with reported outcomes
      with sorafenib. The results highlight the need for a differentiated approach to
      therapeutic recommendations for patients with BCLC C.

PMID- 27714644
TI  - Prognostic Value of Lymph Node Status and Extent of Lymphadenectomy in Pancreatic
      Neuroendocrine Tumors Confined To and Extending Beyond the Pancreas.
AB  - BACKGROUND: The impact of lymph node (LN) status and lymphadenectomy (LA) on
      survival in pancreatic neuroendocrine tumors (pNETs) remains controversial. We
      evaluated the impact of tumor extension and grade on nodal metastasis and
      survival. METHODS: Surgical pNET patients were queried in the Surveillance
      Epidemiology and End Results (SEER) database (1998-2012, N = 981). Factors
      associated with LN status were analyzed by logistic regression and by Cox
      analyses. RESULTS: For T1-T2 tumors, N status was associated only with tumor
      size. N status (p = 0.001), grade (p < 0.001), age (p = 0.001), and sex (p =
      0.007) predicted overall survival (OS). For T3-T4, grade (p < 0.001), sex (p =
      0.004), size (p = 0.013), and age (p = 0.007) but not N status (p = 0.789)
      predicted OS. For T1-T2, disease-specific survival (DSS; p = 0.003) and OS (p =
      0.008) were longer for N0 vs N1, while N0 vs NX had similar OS (p = 0.59) and DSS
      (p = 0.80). While a difference was seen in DSS for NX vs N1 (p = 0.04), no
      significant difference in OS was seen (p = 0.08). For T3-T4, N status did not
      affect DSS (p = 0.365) or OS (p = 0.454). For all T groups and any N status,
      extended LA (>=10 nodes resected) was not associated with OS. CONCLUSION: While
      in T1-T2 pNET N1 status is a predictor of negative OS, similar outcome between NX
      and N0 supports limited LN resection in selected patients. Extended LA is
      unlikely to be helpful in T3-T4.

PMID- 27714646
TI  - Development of fistula between esophagogastric anastomotic site and cartilage
      portion of trachea after subtotal esophagectomy for cervical esophageal cancer: a
      case report.
AB  - A 65-year-old man with cT3N2M0 stage III cervical esophageal cancer underwent
      subtotal esophagectomy and gastric tube reconstruction through the retrosternal
      route after neoadjuvant chemoradiotherapy. The anastomosis was located adjacent
      to the left side of the trachea, and a circular stapler was used for anastomosis.
      Postoperative anastomotic leakage occurred, and an esophagotracheal fistula
      between the esophagogastric anastomotic site and cartilage portion of the trachea
      was observed on postoperative day 44. The patient underwent division of the
      fistula, direct suturing of the anastomotic leakage site, left pectoralis major
      muscle flap placement, and tracheotomy. He was discharged home on postoperative
      day 120 on an oral diet. All previous reports of tracheobronchial fistula
      describe the occurrence of the fistula at the membranous portion of the trachea.
      The formation of a fistula between the esophagogastric anastomotic site and
      cartilage portion of the trachea is considered a possible complication when a
      high esophagogastric anastomosis is created.

PMID- 27714647
TI  - Metastasis of colon cancer to the thyroid and cervical lymph nodes: a case
      report.
AB  - The incidence of thyroid metastasis among colorectal cancer patients is extremely
      rare. We report a case of colonic adenocarcinoma metastasis to the thyroid gland
      with treatment of lung and liver metastases, in a 61-year-old woman with a
      history of colon cancer. She showed a thyroid mass related to a 3-month history
      of hoarseness. Physical and imaging examinations disclosed a diffuse large
      thyroid mass with swollen cervical lymph nodes. Fine-needle aspiration cytology
      of the thyroid mass suggested malignancy. The patient underwent total
      thyroidectomy. Histopathological examination and immunohistochemical staining
      revealed adenocarcinoma, which was consistent with a diagnosis of metastases from
      primary colon cancer to the thyroid and cervical lymph nodes. At 2 years after
      thyroid surgery, the patient has been continuing outpatient chemotherapy for the
      lung and liver metastases. Thyroidectomy appeared to both relieve the patient and
      prevent local symptoms.

PMID- 27714648
TI  - Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu syndrome).

PMID- 27714645
TI  - The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases:
      Implications for Stroke.
AB  - Research on commensal microbiota and its contribution to health and disease is a
      new and very dynamically developing field of biology and medicine. Recent
      experimental and clinical investigations underscore the importance of gut
      microbiota in the pathogenesis and course of stroke. Importantly, microbiota may
      influence the outcome of cerebral ischemia by modulating central nervous system
      antigen-specific immune responses. In this review we summarize studies linking
      gut microbiota with physiological function and disorders of the central nervous
      system. Based on these insights we speculate about targeting the gut microbiome
      in order to treat stroke.

PMID- 27714650
TI  - Molecular Profiling of Synchronous Colon Cancers and Anaplastic Thyroid Cancer in
      a Patient with Lynch Syndrome.

PMID- 27714649
TI  - Telephone-Delivered Stepped Collaborative Care for Treating Anxiety in Primary
      Care: A Randomized Controlled Trial.
AB  - BACKGROUND: Collaborative care for depression is more effective in improving
      treatment outcomes than primary care physicians' (PCPs) usual care (UC). However,
      few trials of collaborative care have targeted anxiety. OBJECTIVE: To examine the
      impact and 12-month durability of a centralized, telephone-delivered, stepped
      collaborative care intervention (CC) for treating anxiety disorders across a
      network of primary care practices. DESIGN: Randomized controlled trial with
      blinded outcome assessments. PARTICIPANTS: A total of 329 patients aged 18-64
      referred by their PCPs in response to an electronic medical record (EMR) prompt.
      They include 250 highly anxious patients randomized to either CC or to UC, and 79
      moderately anxious patients who were triaged to a watchful waiting (WW) cohort
      and later randomized if their conditions clinically deteriorated. INTERVENTION:
      Twelve months of telephone-delivered CC involving non-mental health professionals
      who provided patients with basic psycho-education, assessed preferences for
      guideline-based pharmacotherapy, monitored treatment responses, and informed PCPs
      of their patients' care preferences and progress via the EMR. MAIN MEASURES:
      Mental health-related quality of life ([HRQoL]; SF-36 MCS); secondary outcomes:
      anxiety (Hamilton Anxiety Rating Scale [SIGH-A], Panic Disorder Severity Scale)
      and mood (PHQ-9). KEY RESULTS: At 12-month follow-up, highly anxious patients
      randomized to CC reported improved mental HRQoL (effect size [ES]: 0.38 [95 % CI:
      0.13-0.63]; P = 0.003), anxiety (SIGH-A ES: 0.30 [0.05-0.55]; P = 0.02), and mood
      (ES: 0.45 [0.19-0.71] P = 0.001) versus UC. These improvements were sustained for
      12 months among African-Americans (ES: 0.70-1.14) and men (ES: 0.43-0.93). Of the
      79 WW patients, 29 % met severity criteria for randomization, and regardless of
      treatment assignment, WW patients reported fewer anxiety and mood symptoms and
      better mental HRQoL over the full 24-month follow-up period than highly anxious
      patients who were randomized at baseline. CONCLUSIONS: Telephone-delivered,
      centralized, stepped CC improves mental HRQoL, anxiety and mood symptoms. These
      improvements were durable and particularly evident among those most anxious at
      baseline, and among African-Americans and men.

PMID- 27714652
TI  - A Case of Ruptured Adult Embryonal Sarcoma of the Liver with Excellent Outcome
      After Neoadjuvant Chemotherapy.

PMID- 27714651
TI  - Comparison of FOLFIRINOX Chemotherapy with Other Regimens in Patients with
      Biliary Tract Cancers: a Retrospective Study.
AB  - PURPOSE: The aim of this retrospective study was to compare the different
      treatment options of patients with advanced biliary tract carcinoma (BTC) who
      were treated with platinum-gemcitabine (CG) or platinum-5-fluorouracil (CF) or 5
      Fluorouracil-oxaliplatin-irinotecan (FOLFIRINOX) chemotherapy. METHODS: We
      included the patients with advanced BTC who were registered at the Department of
      Oncology in Gaziantep University between January 2008 and January 2016. The
      following data were analyzed: disease control rate (DCR), progression free
      survival (PFS) of first and second-line of chemotherapy, and overall survival
      (OS). Kaplan-Meier method and Log-rank test was used to compare two survival
      curves, and hazard regression model was used to evaluate risk factors for PFS.
      RESULT: Ninety-two patients were recruited. 53 (57.6 %), 27 (29.3 %), and 12 (13
      %) patients received CG, CF, and FOLFIRINOX regimen as first-line chemotherapy,
      respectively. Median PFS and DCR of CG group were 22 weeks and 56.6 %, and these
      were 12 weeks and 44.4 % for CF group, and 9 weeks and 41.7 % for FOLFIRINOX
      group. Median OS of CG, CF, and FOLFIRINOX groups was 28, 21,and 23.5 weeks,
      respectively (p = 0.497). Second-line PFS of fluoropyrimidine-based chemotherapy
      group and gemcitabine-based chemotherapy group was 12 vs. 14 weeks (p = 0.988).
      Second-line PFS of FOLFIRINOX was 20 weeks, whereas it was 14 weeks for other
      fuoropyrimidine-based chemotherapies (p = 0.190). CONCLUSIONS: This was the first
      study evaluating the FOLFIRINOX regimen in BTC. Cisplatin-gemcitabine therapy
      still provides better survival in BCT. However, FOLFIRINOX can be an option in
      the second-line treatment of BTC patients who are eligible for chemotherapy.

PMID- 27714654
TI  - Physical Activity, Endurance Exercise, and Excess-Can One Overdose?
AB  - OPINION STATEMENT: Although moderate levels of exercise reduce cardiovascular
      morbidity and mortality in the general population, recent data have questioned
      whether higher doses of physical activity are associated with diminished health
      benefits and adverse outcomes. This review focuses on several issues at the
      center of this controversy including epidemiologic data describing mortality
      trends in those who engage in high levels of physical activity and recent
      observational data suggesting adverse cardiovascular outcomes among long-term
      endurance athletes. Specifically for the endurance athlete, the evidence and
      limitations of the available data associating veteran endurance athletes with an
      increased risk of atrial fibrillation, pathologic, and arrhythmogenic cardiac
      remodeling and accelerated coronary atherosclerosis will be discussed. This
      review will also provide practitioners involved in the care of athletes and
      highly active patients a conceptual framework for these contemporary
      controversies and will highlight key areas of uncertainty that will require
      future research.

PMID- 27714653
TI  - Prognostic Impact of Neutrophil/Lymphocyte Ratio, Platelet Count, CRP, and
      Albumin Levels in Metastatic Colorectal Cancer Patients Treated with FOLFIRI
      Bevacizumab.
AB  - PURPOSE: Metastatic colorectal cancer (mCRC) is a lethal disease and fluorouracil
      leucovorin-irinotecan (FOLFIRI) plus bevacizumab (bev) is a standard approach.
      Hence, there is a strong need for identifying new prognostic factors to show the
      efficacy of FOLFIRI-bev. METHODS: This is a retrospective study including
      patients (n = 90) with mCRC from two centers in Turkey. Neutrophil/lymphocyte
      (N/L) ratio, platelet count, albumin, and C-reactive protein (CRP) were recorded
      before FOLFIRI-bev therapy. The efficacy of these factors on progression-free
      survival (PFS) was analyzed with Kaplan Meier and Cox regression analysis. And
      the cutoff value of N/L ratio was analyzed with ROC analysis. RESULTS: The median
      age was 56 years (range 21-80). Forty-seven percent of patients with N/L ratio
      >2.5 showed progressive disease versus 43 % in patients with N/L ratio <2.5 (p =
      0.025). The median PFS was 8.1 months for the patients with N/L ratio >2.5 versus
      13.5 months for the patients with N/L ratio <2.5 (p = 0.025). At univariate Cox
      regression analysis, high baseline neutrophil count, LDH, N/L ratio, and CRP were
      all significantly associated with poor prognosis. At multivariate Cox regression
      analysis, CRP was confirmed to be a better independent prognostic factor. CRP
      variable was divided into above the upper limit of normal (ULN) and normal value.
      The median PFSs of the patients with normal and above ULN were 11.3 versus 5.8
      months, respectively (p = 0.022). CONCLUSIONS: CRP and N/L ratio are potential
      predictors for advanced mCRC treated with FOLFIRI-bev.

PMID- 27714655
TI  - Performance and microbial community structures of hydrolysis acidification
      process treating azo and anthraquinone dyes in different stages.
AB  - In this study, performance of hydrolysis acidification process treating simulated
      dyeing wastewater containing azo and anthraquinone dyes in different stages was
      investigated. The decolorization ratio, CODCr removal ratio, BOD5/CODCr value,
      and volatile fatty acids (VFAs) production were almost better in stage 1 than
      that in stage 2. Fourier transform infrared spectroscopy (FTIR) and gas
      chromatography-mass spectrometry (GC-MS) confirmed the biodegradation of Reactive
      Black 5 (RB5) and Remazol Brilliant Blue R (RBBR) in hydrolysis acidification
      process. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR
      DGGE) analyses revealed that significant difference of microbial community
      structures existed in stage 1 and 2. The dominant species in stage 1 was related
      to Bacteroidetes group, while the dominant species in stage 2 was related to
      Bacteroidetes and Firmicutes groups. From the results, it could be speculated
      that different dyes' structures might have significant influence on the existence
      and function of different bacterial species, which might supply information for
      bacteria screening and acclimation in the treatment of actual dyeing wastewater.

PMID- 27714656
TI  - Effects of four different phosphorus-locking materials on sediment and water
      quality in Xi'an moat.
AB  - To lower phosphorus concentration in Xi'an moat, four different phosphorus
      locking materials, namely, calcium nitrate, sponge-iron, fly ash, and silica
      alumina clay, were selected in this experiment to study their effects on water
      quality and sediment. Results of the continuous 68-day experiment showed that
      calcium nitrate was the most effective for controlling phosphorus concentration
      in overlying and interstitial water, where the efficiency of locking phosphorus
      was >97 and 90 %, respectively. Meanwhile, the addition of calcium nitrate caused
      Fe/Al-bound phosphorus (Fe/Al-P) content in sediment declining but Ca-bound
      phosphorus (Ca-P) and organic phosphorus (OP) content ascending. The phosphorus
      locking efficiency of sponge-iron in overlying and interstitial water was >72 and
      66 %, respectively. Meanwhile, the total phosphorus (TP), OP, Fe/Al-P, and Ca-P
      content in sediment increased by 33.8, 7.7, 23.1, and 23.1 %, respectively,
      implying that under the action of sponge-iron, the locked phosphorus in sediment
      was mainly inorganic form and the phosphorus-locking efficiency of sponge-iron
      could be stable and persistent. In addition, the phosphorus-locking efficiency of
      fly ash was transient and limited, let alone silica alumina clay had almost no
      capacity for phosphorus-locking efficiency. Therefore, calcium nitrate and sponge
      iron were excellent phosphorus-locking agents to repair the seriously polluted
      water derived from an internal source.

PMID- 27714657
TI  - Accumulation of petroleum hydrocarbons in intracellular lipid bodies of the
      freshwater diatom Synedra acus subsp. radians.
AB  - The accumulation of hydrophobic compounds by phytoplankton plays a crucial role
      in the biogeochemical cycle of persistent organic pollutants (POPs) in aquatic
      environments. We studied the accumulation of polycyclic aromatic hydrocarbons
      (PAHs) in the freshwater diatom Synedra acus subsp. radians during its
      cultivation with crude oil hydrocarbons, using epifluorescent and laser confocal
      microscopy as well as gas chromatography-mass spectrometry (GC/MS) analysis. Our
      results revealed that in the presence of crude oil or an extract of a crude oil/n
      hexane solution (light oil), S. acus subsp. radians accumulated PAHs in its lipid
      bodies. During cultivation in the presence of a crude oil/n-hexane solution, the
      cells selectively accumulated C12-C18 alkanes, with a preference for C15 and C16
      homologues. The length of n-alkane hydrocarbon chains accumulated in cells was
      similar to the acyl chains of fatty acids of the diatom. We therefore suggest
      that the insertion of n-alkanes into the membrane lipid bilayer promotes the
      transmembrane transport of PAH in diatoms. Our results confirm the hypothesis
      that diatoms play a role in the elimination of hydrophobic hydrocarbons from
      aquatic systems.

PMID- 27714659
TI  - Exposure to bisphenol A is directly associated with inflammation in healthy
      Korean adults.
AB  - It was recently discovered that bisphenol A (BPA) and phthalates are
      cardiovascular disruptors. Inflammation is central to the initiation and
      progression of cardiovascular disease (CVD). This study evaluated whether BPA and
      different phthalate metabolites are associated with the inflammation marker high
      sensitivity C-reactive protein (hs-CRP) in healthy Korean adults. This research
      is part of an ongoing, population-based study of Korean adults (30-64 years of
      age) conducted at the Cardiovascular and Metabolic Diseases Etiology Research
      Center (CMERC). The study enrolled 200 healthy volunteers (96 men, 104 women).
      Plasma hs-CRP was measured as an inflammation marker. BPA and five phthalate
      metabolites in urine were analyzed by using liquid chromatography/tandem mass
      spectrometry. BPA and monobenzyl phthalate (MBzP) differed significantly between
      the low-hs-CRP (<2 mg/L) and high-hs-CRP (>=2 mg/L) groups. BPA and MBzP were
      related to hs-CRP in an inverted L-shaped manner. High BPA levels (>=75th
      percentile) had significant odd ratios (ORs) for high hs-CRP even after adjusting
      for confounding factors related to obesity and insulin resistance, such as
      visceral fat volume, body mass index (BMI), adiponectin, high-density lipoprotein
      (HDL) cholesterol, hemoglobin A1c (HbA1c), and homeostasis model assessment of
      insulin resistance (HOMA-IR) (OR = 2.85; 95 % CI, 1.16-6.97). However, there was
      no significant association for MBzP >=75th percentile. BPA was significantly
      related to high hs-CRP, even after adjusting for factors related to obesity and
      insulin resistance. Therefore, BPA could have a direct relationship with systemic
      inflammation regardless of obesity or insulin resistance.

PMID- 27714661
TI  - The role of visible light active TiO2 specimens on the solar photocatalytic
      disinfection of E. coli.
AB  - Solar photocatalytic disinfection efficiency of novel visible light activated
      (VLA) photocatalysts was evaluated with the aim of assessing inactivation of
      Escherichia coli as the pathogen indicator organism present in drinking water.
      Influence of humic acid (HA) on the photocatalytic disinfection efficiency of the
      specified VLA TiO2 specimens i.e., N-doped, Se-doped, and Se-N co-doped TiO2 was
      also investigated. Photocatalytic disinfection efficiency was assessed by the
      enumeration of bacteria following selected irradiation periods. Degradation and
      compositional changes in organic matter (OM) was also tracked by means of UV-vis
      and advanced fluorescence spectroscopic (EEM features) parameters. Photocatalytic
      mineralization of the organic matter was followed by dissolved organic carbon
      contents. Presence of HA as a model organic compound of natural organic matter
      (NOM) displayed a retardation effect on solar photocatalytic abatement of E.
      coli. However, no distinctly different effect was observed under solar photolytic
      conditions due to the presence of HA. Regrowth of E. coli could not be assessed
      under the specified experimental conditions. A comparison was introduced with
      respect to the use of undoped TiO2 P-25 as the photocatalyst.

PMID- 27714662
TI  - Personality and uveitis.
AB  - BACKGROUND: Psycho-immunology is an emerging branch of science which studies the
      interaction between the brain and the immune system. The purpose of this study is
      to identify the types of personality factors in patients with non-infectious
      uveitis and to find its association with a particular uveitic entity if any. This
      is a prospective, observational, case-control study of 186 patients with non
      infectious uveitis (group A) and controls from general ophthalmology outpatient
      department (group B). "Global 5/SLOAN" personality questionnaire was used which
      is based on the five-factor theory of personality which describes personality
      factors based on the presence or absence of five primary dimensions, viz
      extroversion, orderliness, emotional stability, accommodation, and intellectual
      curiosity. Personality factors of patients from groups A and B were compared.
      History of present illness, clinical diagnosis, details of systemic ailment, and
      demographic information were collected. RESULTS: Group A comprised HLA-B27
      related uveitis (n = 30), uveitis due to sarcoidosis (n = 10), Vogt-Koyanagi
      Harada syndrome (n = 5), sclero-kerato-uveitis due to rheumatoid arthritis (n =
      5), and idiopathic uveitis in rest. Forty-five patients with uveitis had
      associated systemic ailment. Uveitis patients (n = 56) showed positive
      personality trait: S (social), C (calm), O (organized), A (accommodative), and I
      (inquisitive). In contrast, the control group (group B) which mainly comprised
      patients with non-pathological refractive error and visually insignificant
      cataract showed more number of negative personality traits (n = 62): R
      (reserved), L (limbic), U (unstructured), E (egocentric), and N (non-curious).
      This difference between the uveitis and control group was found to be
      statistically significant (p <= 0.001). The difference was also statistically
      significant for O (p = 0.008), U (p = 0.004), and C (p = 0.022) with chi-square
      test. Calm personality was found to be significantly associated with HLA-B27
      related uveitis (p = 0.002). N, S, and A traits were seen almost equal in numbers
      in both the groups. U trait was absent in group A, whereas I trait had negligible
      presence in group B. CONCLUSIONS: Our finding of an association between organized
      personality type and uveitis and calm personality and HLA-B27-related uveitis
      warrants further studies to understand the complex mechanism of psycho-immunology
      in uveitis.

PMID- 27714660
TI  - Silica dioxide nanoparticles combined with cold exposure induce stronger systemic
      inflammatory response.
AB  - Growing concern has been raised over the potential hazard of nanoparticles (NPs)
      on human health from ambient particulate air pollution. Silicon dioxide (SiO2)
      NPs are one of the most widely used nanoparticles in many sectors of industry.
      Research on NPs has focused mainly on their toxicity in organs. Meanwhile, NPs
      are present in the air year-round, but are more serious in winter. Thus, the aim
      of this study was to evaluate the inflammatory response to SiO2 NPs using in vivo
      test systems. The composition of particulate matter is complicated; however,
      elemental silicon accounts for a significant proportion. Cold exposure can induce
      many kinds of systemic reactions. Thus, the second aim of this study was also to
      evaluate the combined effect of NPs and cold exposure on human health. There is
      little research on the combined effects of nanoparticles and cold on
      inflammation. Sprague-Dawley rats were randomly divided into four groups: those
      exposed to SiO2 NPs by intratracheal instillation, those exposed to at 4  degrees
      C 4 h/day for 4 weeks, a combined SiO2 NPs and cold exposure group, and a control
      group. Inflammatory cell infiltration in the lungs was mainly observed after
      exposure to SiO2 NPs or cold. Hematoxylin and eosin staining revealed that
      inflammation of the lungs was more serious in the combined group. In the white
      adipose tissue and brown adipose tissue of the combined groups, the mRNA
      expressions of pro-inflammatory cytokines were upregulated. In conclusion, SiO2
      NPs combined with cold exposure induced a stronger systemic inflammatory
      response, accompanied by more serious health hazards.

PMID- 27714663
TI  - Brain developmental venous anomaly thrombosis.

PMID- 27714664
TI  - Megaesophagus in an elderly man with achalasia: a "not so benign" condition.

PMID- 27714658
TI  - A systematic review on the adverse health effects of di-2-ethylhexyl phthalate.
AB  - Di (ethylhexyl) phthalate (DEHP) is a global environmental pollutant. This study
      aims to systematically review the literature on health effects of exposure to
      DEHP including effects on reproductive health, carcinogenesis, pregnancy outcome,
      and respiratory system. The literature search was done through Scopus, ISI Web of
      Science, Google Scholar, PubMed, Medline, and the reference lists of previous
      review articles to identify relevant articles published to June 2016 in each
      subject area. The inclusion criteria were as follows: original research, cross
      sectional studies, case-control studies, cohort studies, interventional studies,
      and review articles. Both human and animal studies were included. The search was
      limited to English language papers. Conference papers, editorials, and letters
      were not included. The systematic review was conducted and reported in accordance
      with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) statement. Overall, 152 of the 407 papers met the inclusion criteria. We
      provided an up-to-date comprehensive and critical assessment of both human and
      animal studies undertaken to explore the effects of DEHP. It revealed that in
      experimental studies, exposure to DEHP mainly targeted the reproductive,
      neurodevelopment, and respiratory systems. Human studies reported that exposure
      to this contaminant had carcinogenic effects and influenced neurodevelopment in
      early life. This systematic review underscored the adverse health effects of DEHP
      for pregnant women and the pediatric age group. It summarizes different response
      of humans and experimental animals to DEHP exposure, and some suggested
      underlying mechanisms.

PMID- 27714665
TI  - Picture-word interference is a Stroop effect: A theoretical analysis and new
      empirical findings.
AB  - The picture-word interference (PWI) paradigm and the Stroop color-word
      interference task are often assumed to reflect the same underlying processes. On
      the basis of a PRP study, Dell'Acqua et al. (Psychonomic Bulletin & Review, 14:
      717-722, 2007) argued that this assumption is incorrect. In this article, we
      first discuss the definitions of Stroop- and picture-word interference. Next, we
      argue that both effects consist of at least four components that correspond to
      four characteristics of the distractor word: (1) response-set membership, (2)
      task relevance, (3) semantic relatedness, and (4) lexicality. On the basis of
      this theoretical analysis, we conclude that the typical Stroop effect and the
      typical PWI effect mainly differ in the relative contributions of these four
      components. Finally, the results of an interference task are reported in which
      only the nature of the target - color or picture - was manipulated and all other
      distractor task characteristics were kept constant. The results showed no
      difference between color and picture targets with respect to all behavioral
      measures examined. We conclude that the assumption that the same processes
      underlie verbal interference in color and picture naming is warranted.

PMID- 27714666
TI  - Sex differences in virtual navigation influenced by scale and navigation
      experience.
AB  - The Morris water maze is a spatial abilities test adapted from the animal spatial
      cognition literature and has been studied in the context of sex differences in
      humans. This is because its standard design, which manipulates proximal (close)
      and distal (far) cues, applies to human navigation. However, virtual Morris water
      mazes test navigation skills on a scale that is vastly smaller than natural human
      navigation. Many researchers have argued that navigating in large and small
      scales is fundamentally different, and small-scale navigation might not simulate
      natural human navigation. Other work has suggested that navigation experience
      could influence spatial skills. To address the question of how individual
      differences influence navigational abilities in differently scaled environments,
      we employed both a large- (146.4 m in diameter) and a traditional- (36.6 m in
      diameter) scaled virtual Morris water maze along with a novel measure of
      navigation experience (lifetime mobility). We found sex differences on the small
      maze in the distal cue condition only, but in both cue-conditions on the large
      maze. Also, individual differences in navigation experience modulated navigation
      performance on the virtual water maze, showing that higher mobility was related
      to better performance with proximal cues for only females on the small maze, but
      for both males and females on the large maze.

PMID- 27714668
TI  - Introduction to SCiP Special Issue.

PMID- 27714667
TI  - Challenges in the management of patients with maple syrup urine disease diagnosed
      by newborn screening in a developing country.
AB  - Maple syrup urine disease (MSUD) is a rare inborn error of metabolism resulting
      from a deficiency in the branched-chain alpha-ketoacid dehydrogenase complex.
      MSUD has been reported to be the most common inborn error of metabolism in the
      Philippines. We described all patients with maple syrup urine disease patients
      diagnosed through newborn screening during its first 2 years of implementation
      and the challenges encountered during their medical management. There were 24
      patients diagnosed with maple syrup urine disease for the 2-year period. All
      patients needed hospital admission. The most common complication during hospital
      admission was infection, needing intravenous antibiotics which were given to 21
      of the patients. Out of the 24 diagnosed, 16 patients are alive, while eight have
      died. Several neurologic and non-neurologic complications have been observed
      during the follow-up of the patients. The common challenges of MSUD management in
      a low-resource setting identified in this study were late diagnosis, lack of
      access to metabolic specialists and medical supplies, nosocomial septicemia, and
      protein deficiency. Aside from early properly timed collection, improvement in
      other logistical concerns will also help in earlier diagnosis. Mechanisms of
      transfer of critically ill patients must be improved. Hospitals in difficult-to
      reach areas must be equipped to handle critical metabolic cases when transfers
      are not possible. Newborn screening has been proven to improve outcome in
      patients with MSUD but the success of the program in preventing disability is
      also dependent on improvements in other aspects of healthcare.

PMID- 27714670
TI  - Mechanisms, Imaging, and Therapy in Stroke Recovery.

PMID- 27714672
TI  - miR-203 is a predictive biomarker for colorectal cancer and its expression is
      associated with BIRC5.
AB  - The purpose of this study was to explore the role of miR-203 in colorectal cancer
      (CRC) and evaluate the correlation between miR-203 and BIRC5. The expressions of
      miR-203 in the tissues of 122 CRC patients (with non-tumor tissues as controls)
      and those from 30 healthy donors were detected by TaqMan(r) MicroRNA assay.
      BIRC5s expressions in CRC and non-tumor tissues were detected by
      immunohistochemistry. Significantly less miR-203 was expressed in CRC tissues (P
      < 0.05) than in non-tumor tissues. Furthermore, low expression level of miR-203
      was correlated with distant metastasis (DM), lymph node metastasis (LNM), and TNM
      stage (P < 0.05), but there were no significant differences between tumor size or
      gender. The positive expression rates of BIRC5 in CRC and non-tumor tissues were
      73.77 % (90/122) and 30.32 % (37/122), respectively. The expression intensity of
      BIRC5 in CRC was significantly higher than that of non-tumor tissues (P < 0.05).
      It was significantly correlated with DM, LNM, and TNM stage (P < 0.05). Finally,
      miR-203 expression was negatively associated with that of BIRC5 (r = -0.8150, P <
      0.05). In conclusion, miR-203 was down-regulated in CRC tissues and involved in
      the onset and progression of CRC. The expressions of miR-203 and BIRC5 in CRC
      were significantly negatively correlated, suggesting that BIRC5 may be regulated
      by miR-203. miR-203 is a potential suppressor and predictive biomarker for CRC.

PMID- 27714669
TI  - A Post-stroke Therapeutic Regimen with Omega-3 Polyunsaturated Fatty Acids that
      Promotes White Matter Integrity and Beneficial Microglial Responses after
      Cerebral Ischemia.
AB  - White matter injury induced by ischemic stroke elicits sensorimotor impairments,
      which can be further deteriorated by persistent proinflammatory responses. We
      previously reported that delayed and repeated treatments with omega-3
      polyunsaturated fatty acids (n-3 PUFAs) improve spatial cognitive functions and
      hippocampal integrity after ischemic stroke. In the present study, we report a
      post-stroke n-3 PUFA therapeutic regimen that not only confers protection against
      neuronal loss in the gray matter but also promotes white matter integrity.
      Beginning 2 h after 60 min of middle cerebral artery occlusion (MCAO), mice were
      randomly assigned to receive intraperitoneal docosahexaenoic acid (DHA)
      injections (10 mg/kg, daily for 14 days), alone or in combination with dietary
      fish oil (FO) supplements starting 5 days after MCAO. Sensorimotor functions,
      gray and white matter injury, and microglial responses were examined up to 28
      days after MCAO. Our results showed that DHA and FO combined treatment
      facilitated long-term sensorimotor recovery and demonstrated greater beneficial
      effect than DHA injections alone. Mechanistically, n-3 PUFAs not only offered
      direct protection on white matter components, such as oligodendrocytes, but also
      potentiated microglial M2 polarization, which may be important for white matter
      repair. Notably, the improved white matter integrity and increased M2 microglia
      were strongly linked to the mitigation of sensorimotor deficits after stroke upon
      n-3 PUFA treatments. Together, our results suggest that post-stroke DHA
      injections in combination with FO dietary supplement benefit white matter
      restoration and microglial responses, thereby dictating long-term functional
      improvements.

PMID- 27714671
TI  - BRCA1 and MDM2 as independent blood-based biomarkers of head and neck cancer.
AB  - We investigated the role of BRCA1, MDM2, and p53 in the pathogenesis of head and
      neck cancer (HNC) and evaluated their potential utility as blood-based predictive
      biomarkers of HNC. Immunostaining of tissue biopsies and whole blood lymphocytes
      (WBL) of 36 HNC patients were evaluated by immunohistochemistry (IHC) and
      immunocytochemistry (ICC), respectively. The staining intensities of BRCA1 and
      MDM2 in matched tissue and blood samples were significantly associated with
      cancer stage. Furthermore, the cellular levels of BRCA1, MDM2, and p53 were
      evaluated in peripheral blood lymphocytes (PBL) of 134 HNC patients and 126
      controls by slot blotting. Expression levels of all three proteins in PBL of HNC
      patients varied significantly with respect to those of controls (p < 0.0001) with
      BRCA1 downregulated to 75 % of control and MDM2 and p53 upregulated to 1.7- and
      1.4-fold the control level, respectively. Moreover, positive correlation was
      observed between expression levels of BRCA1, MDM2, and p53 in matched tissue
      biopsies-WBL (r s = 0.840, 0.754, and 0.806, respectively), tissue biopsies-PBL
      (r s = 0.745, 0.736, and 0.776, respectively), and PBL-WBL (r s = 0.709, 0.758,
      and 0.740, respectively), validating the hypothesis that these proteins may serve
      as blood-based biomarkers of HNC. Bias-corrected and accelerated (BCa) bootstrap
      cross-validation estimation of receiver operating characteristics (ROC) analysis
      established BRCA1 (AUC = 0.726, sensitivity = 89 %, NPV = 82 %) and MDM2 (AUC =
      0.827, sensitivity = 85 %, NPV = 81 %) as predictive biomarkers for HNC. In
      conclusion, this study suggests that BRCA1 and MDM2 play a crucial role in the
      pathogenesis of HNC and could be used independently as predictive biomarkers for
      HNC.

PMID- 27714673
TI  - Regulation of exosomes released from normal ovarian epithelial cells and ovarian
      cancer cells.
AB  - As important cell to cell communicator, exosomes carry a range of bioactive
      molecules which can significantly influence phenotype of recipient cells.
      Inhibiting or removing cancer cell-derived exosomes are of therapeutic interest.
      However, regulation of secretion and release mechanism of exosomes is still
      unclear. To explore the regulation of exosomes released from normal ovarian
      epithelial cells and ovarian cancer cells, a normal ovarian epithelial cell line
      and three ovarian epithelial cancer cell lines were utilized to investigate their
      exosomes' release and regulation. A cervical cancer cell SiHa was used for
      identifying tissue specificity. NanoSight NS500 was used to quantify exosome
      numbers. Exosomes were labeled and observed by confocal microscopy to investigate
      their interaction with different ovarian cell lines. Exosomes released from
      normal or ovarian cancer cells were regulated by the extracellular exosomes.
      Exosome release was inhibited with the extracellular exosome concentration
      increase. Exosomes from normal ovarian cell and cervical cancer cell also
      inhibited ovarian cancer cell-derived exosome release, and there was no tissue
      specificity. PKH26-labeled exosomes from normal ovarian cell and cervical cancer
      cell were uptaken by ovarian cancer cells. Release of exosomes from ovarian
      cancer cell is regulated by a feedback mechanism without tissue specificity. This
      may provide a therapeutic approach to control the release of exosomes from
      ovarian cancer cells.

PMID- 27714674
TI  - Highly expressed lncRNA CRNDE promotes cell proliferation through Wnt/beta
      catenin signaling in renal cell carcinoma.
AB  - Recently, numerous studies revealed that long non-coding RNAs (lncRNAs) play
      complex roles in the field of tumor biology, while the functions of lncRNA in
      renal cell carcinoma (RCC) remain largely unknown. In the current study, we
      retrieved Oncomine database and found a lncRNA colorectal neoplasia
      differentially expressed (CRNDE) which is highly expressed in different cohorts
      of RCC patients; this clue reminds us that CRNDE might exert its functions in RCC
      tumorigenesis. We then detected the level of CRNDE in fresh RCC tissues and found
      that CRNDE is significantly up-regulated compared with adjacent tissues.
      Furthermore, both loss and gain function assays revealed that CRNDE promotes RCC
      cell proliferation and growth both in vitro and in vivo.In addition, we found
      that CRNDE regulates the cell cycle transition from G0/G1 stage to S stage and
      modulates the expression of CCND1 and CCNE1. Moreover, we further illustrated
      that CRNDE activates Wnt/beta-catenin signaling in RCC cell lines. Taken
      together, in the current study, we found that lncRNA CRNDE is highly expressed in
      RCC malignant tissues and the heightened CRNDE robustly promotes RCC cell
      proliferation through activating Wnt/beta-catenin signaling; our findings enlarge
      our knowledge in the molecular pathology of RCC tumorigenesis.

PMID- 27714676
TI  - Erratum.

PMID- 27714677
TI  - The Sustained Rotavirus Vaccination Impact on Nosocomial Infection, Duration of
      Hospital Stay, and Age: The RotaBIS Study (2005-2012).
AB  - INTRODUCTION: The benefits of rotavirus (RV) vaccination in developed countries
      have focused on reductions in mortality, hospitalization and medical visits, and
      herd protection. We investigated other aspects related to RV-induced nosocomial
      infection, duration of hospital stay, age shift, and sustained vaccine impact
      (VI) over time. METHOD: RotaBIS (Rotavirus Belgian Impact Study;
      ClinicalTrials.gov identifier, NCT01563146) annually collects retrospective data
      on hospitalization linked to RV testing in children up to 5 years old from 11
      pediatric wards located all over Belgium. Data from 2005 to 2012 have been split
      in pre- (2005-2006) and post-vaccination (2007-2012) period. Information was
      collected on age, gender, RV test result, nosocomial infection caused by RV and
      duration of hospital stay. RESULTS: Over the 6-year period after the introduction
      of the RV vaccine, an 85% reduction in nosocomial infections was observed (221 in
      2005 to 33 in 2012, p < 0.001). A significant reduction of almost 2 days in
      average duration of hospital stay per event was observed overall (7.62 days in
      2005 to 5.77 days in 2012, p < 0.001). The difference is mainly explained by the
      higher reduction in number of nosocomial infections. A pronounced age shift
      (+24%, p < 0.01) of RV nosocomial infection to infants <=2 months old was
      observed, increasing with length of post-vaccination period. VI was maintained
      over the follow-up (+/-79% VI per birth cohort). A decrease was seen depending on
      age, 85% (95% CI 76-91%) in the youngest to 63% (95% CI 22-92%) in the oldest age
      group. CONCLUSION: The higher reduction in nosocomial infection may affect the
      overall average duration of hospital stay for RV infection. No change in VI by
      birth cohort, but a reduction by age group was observed. These findings could be
      important for decision-makers considering the introduction of universal mass RV
      vaccination programs. TRIAL REGISTRATION: ClinicalTrials.gov identifier,
      NCT01563146. FUNDING: GlaxoSmithKline Biologicals SA (Rixensart, Belgium).

PMID- 27714679
TI  - Survey of electric bidet toilet use among community dwelling Japanese people and
      correlates for an itch on the anus.
AB  - OBJECTIVES: We conducted a survey to investigate the use of bidet toilets among
      community dwelling Japanese people and explored the correlates for an itch on the
      anus. METHODS: A questionnaire-based survey was conducted among a convenience
      sample of individuals, who were derived from outpatients and employees of Kameda
      Medical Center, and students and employees of two technical colleges. RESULTS: A
      total of 4,963 respondents were evaluated in this study, 55 % of whom used bidet
      toilets either before or after defecation, and at least 30 % of bidet users
      washed the anus before defecation, partly to aid defecation. Men rather than
      women, and older people (aged >=50 years) rather than younger people used bidets
      more actively. Logistic regression analysis showed that the correlates for an
      itch on the anus included male sex, younger age, washing the anus before
      defecation, warmer water for washing the anus after defecation, and the frequency
      of fecal leakage. CONCLUSIONS: Nearly, one-third of bidet toilet users washed the
      anus before defecation. An itch on the anus may be associated with the active use
      of bidets.

PMID- 27714675
TI  - The roles of microRNAs related with progression and metastasis in human cancers.
AB  - Metastasis is an important factor in predicting the prognosis of the patients
      with cancers and contributes to high cancer-related mortality. Recent studies
      indicated that microRNAs (miRNAs) played a functional role in the initiation and
      progression of human malignancies. MicroRNAs are small non-coding RNAs of about
      22 nucleotides in length that can induce messenger RNA (mRNA) degradation or
      repress mRNA translation by binding to the 3' untranslated region (3'-UTR) of
      their target genes. Overwhelming reports indicated that miRNAs could regulate
      cancer invasion and metastasis via epithelial-to-mesenchymal transition (EMT)
      related and/or non-EMT-related mechanisms. In this review, we concentrate on the
      underlying mechanisms of miRNAs in regulating cancer progression and metastasis.

PMID- 27714678
TI  - Roles of defective ALDH2 polymorphism on liver protection and cancer development.
AB  - Because serum transaminases elevate alcohol dose dependently as a consequence of
      liver injury, they serve as useful biological markers of excessive drinking.
      However, these markers are inadequate in individuals with a defective allele of
      the aldehyde dehydrogenase 2 gene, ALDH2*2, because they show a different
      correlation with the amount of ethanol. For example, the serum alanine
      aminotransferase (ALT) level could become even lower than the baseline after
      alcohol intake in ALDH2*2 carriers. In fact, multiple studies suggest that
      ALDH2*2 is a hepato-protective factor in healthy individuals. Importantly,
      excessive drinking is particularly dangerous in carriers of ALDH2*2 because the
      risk of alcohol-related cancer is much higher than that for ALDH2*1/*1 carriers.
      Without recognizing the genotype interaction on serum transaminase, the
      opportunity to warn people about potential cancer risks is missed owing to
      incorrect interpretation. This is particularly important in East Asian countries
      where approximately half of the population carries the ALDH2*2 allele. To date,
      the mechanism of liver protection from ethanol load in individuals with ALDH2*2
      has not been fully elucidated. However, some reasonable mechanisms have been
      suggested by experimental studies, including remodelling of detoxifying systems.
      Further studies to uncover the whole mechanism are anticipated.

PMID- 27714680
TI  - Live donor liver transplantation for alcoholic hepatitis.
AB  - Liver transplantation is a definitive therapy for patients with end-stage liver
      disease and cirrhosis, with improvement in survival and quality of life. Patients
      are carefully screened and selected for this modality of treatment to achieve
      maximum survival benefit. For example, a patient with hepatocellular carcinoma is
      a candidate if he or she is within Milan criteria and has no significant
      comorbidity. Similarly, patients with alcoholic cirrhosis are transplant
      candidates if they are deemed to have been rehabilitated from abusive alcohol
      consumption and are at low risk for recidivism. More recently, carefully selected
      patients with alcoholic hepatitis have been successfully transplanted. The
      preferred transplantation modality is cadaveric liver transplantation. However,
      living donor liver transplantation is carried out if there is no cadaveric liver
      organ allocation system, or if the patient is deemed to be at low priority for
      cadaveric organ transplantation based on the allocation system. Living donor
      liver transplantation for alcoholic hepatitis needs to be addressed with this
      background in mind.

PMID- 27714682
TI  - Glial Cells and Integrity of the Nervous System.
AB  - Today, there is enormous progress in understanding the function of glial cells,
      including astroglia, oligodendroglia, Schwann cells, and microglia. Around 150
      years ago, glia were viewed as a glue among neurons. During the course of the
      twentieth century, microglia were discovered and neuroscientists' views evolved
      toward considering glia only as auxiliary cells of neurons. However, over the
      last two to three decades, glial cells' importance has been reconsidered because
      of the evidence on their involvement in defining central nervous system
      architecture, brain metabolism, the survival of neurons, development and
      modulation of synaptic transmission, propagation of nerve impulses, and many
      other physiological functions. Furthermore, increasing evidence shows that glia
      are involved in the mechanisms of a broad spectrum of pathologies of the nervous
      system, including some psychiatric diseases, epilepsy, and neurodegenerative
      diseases to mention a few. It appears safe to say that no neurological disease
      can be understood without considering neuron-glia crosstalk. Thus, this book aims
      to show different roles played by glia in the healthy and diseased nervous
      system, highlighting some of their properties while considering that the various
      glial cell types are essential components not only for cell function and
      integration among neurons, but also for the emergence of important brain
      homeostasis.

PMID- 27714683
TI  - NG2-glia, More Than Progenitor Cells.
AB  - NG2-glia are a mysterious and ubiquitous glial population with a highly branched
      morphology. Initial studies suggested that their unique function is the
      generation and maintenance of oligodendrocytes in the central nervous system
      (CNS), important for proper myelination and therefore for axonal support and fast
      conduction velocity. Over the last years this simplistic notion has been
      dramatically changed: the wide and homogeneous distribution of NG2-glia within
      all areas of the developing CNS that is maintained during the whole lifespan,
      their potential to also differentiate into other cell types in a spatiotemporal
      manner, their active capability of maintaining their population and their dynamic
      behavior in altered conditions have raised the question: are NG2-glia simple
      progenitor cells or do they play further major roles in the normal function of
      the CNS? In this chapter, we will discuss some important features of NG2-glia
      like their homeostatic distribution in the CNS and their potential to
      differentiate into diverse cell types. Additionally, we will give some further
      insights into the properties that these cells have, like the ability to form
      synapses with neurons and their plastic behavior triggered by neuronal activity,
      suggesting that they may play a role specifically in myelin and more generally in
      brain plasticity. Finally, we will briefly review their behavior in disease
      models suggesting that their function is extended to repair the brain after
      insult.

PMID- 27714684
TI  - Pharmacological Tools to Study the Role of Astrocytes in Neural Network
      Functions.
AB  - Despite that astrocytes and microglia do not communicate by electrical impulses,
      they can efficiently communicate among them, with each other and with neurons, to
      participate in complex neural functions requiring broad cell-communication and
      long-lasting regulation of brain function. Glial cells express many receptors in
      common with neurons; secrete gliotransmitters as well as neurotrophic and
      neuroinflammatory factors, which allow them to modulate synaptic transmission and
      neural excitability. All these properties allow glial cells to influence the
      activity of neuronal networks. Thus, the incorporation of glial cell function
      into the understanding of nervous system dynamics will provide a more accurate
      view of brain function. Our current knowledge of glial cell biology is providing
      us with experimental tools to explore their participation in neural network
      modulation. In this chapter, we review some of the classical, as well as some
      recent, pharmacological tools developed for the study of astrocyte's influence in
      neural function. We also provide some examples of the use of these
      pharmacological agents to understand the role of astrocytes in neural network
      function and dysfunction.

PMID- 27714685
TI  - Microglia Function in the Normal Brain.
AB  - The activation of microglia has been recognized for over a century by their
      morphological changes. Long slender microglia acquire a short sturdy ramified
      shape when activated. During the past 20 years, microglia have been accepted as
      an essential cellular component for understanding the pathogenic mechanism of
      many brain diseases, including neurodegenerative diseases. More recently,
      functional studies and imaging in mouse models indicate that microglia are active
      in the healthy central nervous system. It has become evident that microglia
      release several signal molecules that play key roles in the crosstalk among brain
      cells, i.e., astrocytes and oligodendrocytes with neurons, as well as with
      regulatory immune cells. Recent studies also reveal the heterogeneous nature of
      microglia diverse functions depending on development, previous exposure to
      stimulation events, brain region of residence, or pathological state. Subjects to
      approach by future research are still the unresolved questions regarding the
      conditions and mechanisms that render microglia protective, capable of preventing
      or reducing damage, or deleterious, capable of inducing or facilitating the
      progression of neuropathological diseases. This novel knowledge will certainly
      change our view on microglia as therapeutic target, shifting our goal from their
      general silencing to the generation of treatments able to change their activation
      pattern.

PMID- 27714686
TI  - Physiological Functions of Glial Cell Hemichannels.
AB  - The brain performs exceptionally complex and dynamic tasks that depend on the
      coordinated interaction of neurons, glial cells, endothelial cells, pericytes,
      smooth muscle cells, ependymal cells, and circulating blood cells. Among these
      cells, glial cells have emerged as crucial protagonists in the regulation of
      synaptic transmission and neural function. Indeed, these cells express a wide
      range of receptors that enable them to sense changes in neuronal activity and the
      microenvironment by responding locally via the release of bioactive molecules
      known as gliotransmitters. In the central nervous system (CNS), a novel mechanism
      that allows gliotransmission via the opening of hemichannels has been proposed.
      These channels are composed of six protein subunits consisting of connexins or
      pannexins, which are two highly conserved protein families that are encoded by 21
      and 3 genes, respectively, in humans. Typically, glial cell hemichannels exhibit
      low levels of activity, but this activity is sufficient to ensure the release of
      a broad spectrum of gliotransmitters, including ATP, D-serine, glutamate,
      adenosine, and glutathione. Here, we briefly review the current findings
      regarding the effects of the hemichannel-dependent release of gliotransmitters on
      the physiology of the CNS.

PMID- 27714687
TI  - Role of Astrocytes in Central Respiratory Chemoreception.
AB  - Astrocytes perform various homeostatic functions in the nervous system beyond
      that of a supportive or metabolic role for neurons. A growing body of evidence
      indicates that astrocytes are crucial for central respiratory chemoreception.
      This review presents a classical overview of respiratory central chemoreception
      and the new evidence for astrocytes as brainstem sensors in the respiratory
      response to hypercapnia. We review properties of astrocytes for chemosensory
      function and for modulation of the respiratory network. We propose that
      astrocytes not only mediate between CO2/H+ levels and motor responses, but they
      also allow for two emergent functions: (1) Amplifying the responses of intrinsic
      chemosensitive neurons through feedforward signaling via gliotransmitters and;
      (2) Recruiting non-intrinsically chemosensitive cells thanks to volume spreading
      of signals (calcium waves and gliotransmitters) to regions distant from the
      CO2/H+ sensitive domains. Thus, astrocytes may both increase the intensity of the
      neuron responses at the chemosensitive sites and recruit of a greater number of
      respiratory neurons to participate in the response to hypercapnia.

PMID- 27714681
TI  - Asian-Pacific Association for the Study of the Liver (APASL) consensus guidelines
      on invasive and non-invasive assessment of hepatic fibrosis: a 2016 update.
AB  - Hepatic fibrosis is a common pathway leading to liver cirrhosis, which is the end
      result of any injury to the liver. Accurate assessment of the degree of fibrosis
      is important clinically, especially when treatments aimed at reversing fibrosis
      are being evolved. Despite the fact that liver biopsy (LB) has been considered
      the "gold standard" of assessment of hepatic fibrosis, LB is not favored by
      patients or physicians owing to its invasiveness, limitations, sampling errors,
      etc. Therefore, many alternative approaches to assess liver fibrosis are gaining
      more popularity and have assumed great importance, and many data on such
      approaches are being generated. The Asian Pacific Association for the Study of
      the Liver (APASL) set up a working party on liver fibrosis in 2007, with a
      mandate to develop consensus guidelines on various aspects of liver fibrosis
      relevant to disease patterns and clinical practice in the Asia-Pacific region.
      The first consensus guidelines of the APASL recommendations on hepatic fibrosis
      were published in 2009. Due to advances in the field, we present herein the APASL
      2016 updated version on invasive and non-invasive assessment of hepatic fibrosis.
      The process for the development of these consensus guidelines involved review of
      all available published literature by a core group of experts who subsequently
      proposed consensus statements followed by discussion of the contentious issues
      and unanimous approval of the consensus statements. The Oxford System of the
      evidence-based approach was adopted for developing the consensus statements using
      the level of evidence from one (highest) to five (lowest) and grade of
      recommendation from A (strongest) to D (weakest). The topics covered in the
      guidelines include invasive methods (LB and hepatic venous pressure gradient
      measurements), blood tests, conventional radiological methods, elastography
      techniques and cost-effectiveness of hepatic fibrosis assessment methods, in
      addition to fibrosis assessment in special and rare situations.

PMID- 27714688
TI  - Purine Signaling and Microglial Wrapping.
AB  - Microglial cells are highly dynamic cells with processes continuously moving to
      survey the surrounding territory. Microglia possess a broad variety of surface
      receptors and subtle changes in their microenvironment cause microglial cell
      processes to extend, retract, and interact with neuronal synaptic contacts. When
      the nervous system is disturbed, microglia activate, proliferate, and migrate to
      sites of injury in response to alert signals. Released nucleotides like ATP and
      UTP are among the wide range of molecules promoting microglial activation and
      guiding their migration and phagocytic function. The increased concentration of
      nucleotides in the extracellular space could be involved in the microglial
      wrapping found around injured neurons in various pathological conditions,
      especially after peripheral axotomy. Microglial wrappings isolate injured neurons
      from synaptic inputs and facilitate the molecular dialog between endangered or
      injured neurons and activated microglia. Astrocytes may also participate in
      neuronal ensheathment. Degradation of ATP by microglial ecto-nucleotidases and
      the expression of various purine receptors might be decisive in regulating the
      function of enwrapping glial cells and in determining the fate of damaged
      neurons, which may die or may regenerate their axons and survive.

PMID- 27714689
TI  - Oligodendrocytes: Functioning in a Delicate Balance Between High Metabolic
      Requirements and Oxidative Damage.
AB  - The study of the metabolic interactions between myelinating glia and the axons
      they ensheath has blossomed into an area of research much akin to the elucidation
      of the role of astrocytes in tripartite synapses (Tsacopoulos and Magistretti in
      J Neurosci 16:877-885, 1996). Still, unlike astrocytes, rich in cytochrome-P450
      and other anti-oxidative defense mechanisms (Minn et al. in Brain Res Brain Res
      Rev 16:65-82, 1991; Wilson in Can J Physiol Pharmacol. 75:1149-1163, 1997),
      oligodendrocytes can be easily damaged and are particularly sensitive to both
      hypoxia and oxidative stress, especially during their terminal differentiation
      phase and while generating myelin sheaths. In the present review, we will focus
      in the metabolic complexity of oligodendrocytes, particularly during the
      processes of differentiation and myelin deposition, and with a specific emphasis
      in the context of oxidative stress and the intricacies of the iron metabolism of
      the most iron-loaded cells of the central nervous system (CNS).

PMID- 27714690
TI  - Schwann Cell and Axon: An Interlaced Unit-From Action Potential to Phenotype
      Expression.
AB  - Here we propose a model of a peripheral axon with a great deal of autonomy from
      its cell body-the autonomous axon-but with a substantial dependence on its
      ensheathing Schwann cell (SC), the axon-SC unit. We review evidence in several
      fields and show that (i) axons can extend sprouts and grow without the
      concurrence of the cell body, but regulated by SCs; (ii) axons synthesize their
      proteins assisted by SCs that supply them with ribosomes and, probably, with
      mRNAs by way of exosomes; (iii) the molecular organization of the axoplasm, i.e.,
      its phenotype, is regulated by the SC, as illustrated by the axonal microtubular
      content, which is down-regulated by the SC; and (iv) the axon has a program for
      self-destruction that is boosted by the SC. The main novelty of this model axon
      SC unit is that it breaks with the notion that all proteins of the nerve cell are
      specified by its own nucleus. The notion of a collaborative specification of the
      axoplasm by more than one nucleus, which we present here, opens a new dimension
      in the understanding of the nervous system in health and disease and is also a
      frame of reference to understand other tissues or cell associations.

PMID- 27714691
TI  - Age-Dependent Changes in the Activation and Regulation of Microglia.
AB  - As we age, a large number of physiological and molecular changes affect the
      normal functioning of cells, tissues, and the organism as a whole. One of the
      main changes is the establishment of a state of systemic inflammatory activation,
      which has been termed "inflamm-aging"; a mild chronic inflammation of the aging
      organism that reduces the ability to generate an efficient response against
      stressor stimuli. As any other system, the nervous system undergoes these aging
      related changes; the neuroinflammatory state depends mainly on the dysregulated
      activation of microglia, the innate immune cells of the central nervous system
      (CNS) and the principal producers of reactive oxygen species. As the brain ages,
      microglia acquire a phenotype that is increasingly inflammatory and cytotoxic,
      generating a hostile environment for neurons. There is mounting evidence that
      this process facilitates development of neurodegenerative diseases, for which the
      greatest risk factor is age. In this chapter, we will review key aging-associated
      changes occurring in the central nervous system, focusing primarily on the
      changes that occur in aging microglia, the inflammatory and oxidative stressful
      environment they establish, and their impaired regulation. In addition, we will
      discuss the effects of aged microglia on neuronal function and their
      participation in the development of neurodegenerative pathologies such as
      Parkinson's and Alzheimer's diseases.

PMID- 27714692
TI  - Astrocyte Dysfunction in Developmental Neurometabolic Diseases.
AB  - Astrocytes play crucial roles in maintaining brain homeostasis and in
      orchestrating neural development, all through tightly coordinated steps that
      cooperate to maintain the balance needed for normal development. Here, we review
      the alterations in astrocyte functions that contribute to a variety of
      developmental neurometabolic disorders and provide additional data on the
      predominant role of astrocyte dysfunction in the neurometabolic neurodegenerative
      disease glutaric acidemia type I. Finally, we describe some of the therapeutical
      approaches directed to neurometabolic diseases and discuss if astrocytes can be
      possible therapeutic targets for treating these disorders.

PMID- 27714693
TI  - Microglia in Cancer: For Good or for Bad?
AB  - Glioblastoma is a malignant tumor of astrocytic origin that is highly invasive,
      proliferative and angiogenic. Despite current advances in multimodal therapies,
      such as surgery, radio- and chemotherapy, the outcome for patients with
      glioblastoma is nearly always fatal. The glioblastoma microenvironment has a
      tremendous influence over the tumor growth and spread. Microglia and macrophages
      are abundant cells in the tumor mass. Increasing evidence indicates that
      glioblastoma recruits these cell populations and signals in a way that microglia
      and macrophages are subverted to promote tumor progression. In this chapter, we
      discuss some aspects of the interaction between microglia and glioblastoma,
      consequences of this interaction for tumor progression and the possibility of
      microglial cells being used as therapeutic vectors, which opens up new
      alternatives for the development of GBM therapies targeting microglia.

PMID- 27714694
TI  - Peripheral Inflammation and Demyelinating Diseases.
AB  - In recent decades, several neurodegenerative diseases have been shown to be
      exacerbated by systemic inflammatory processes. There is a wide range of
      literature that demonstrates a clear but complex relationship between the central
      nervous system (CNS) and the immunological system, both under naive or
      pathological conditions. In diseased brains, peripheral inflammation can
      transform "primed" microglia into an "active" state, which can trigger stronger
      pathological responses. Demyelinating diseases are a group of neurodegenerative
      diseases characterized by inflammatory lesions associated with demyelination,
      which in turn induces axonal damage, neurodegeneration, and progressive loss of
      function. Among them, the most important are multiple sclerosis (MS) and
      neuromyelitis optica (NMO). In this review, we will analyze the effect of
      specific peripheral inflammatory stimuli in the progression of demyelinating
      diseases and discuss their animal models. In most cases, peripheral immune
      stimuli are exacerbating.

PMID- 27714695
TI  - Regulation of Oligodendrocyte Differentiation and Myelination by Nuclear
      Receptors: Role in Neurodegenerative Disorders.
AB  - During development and through adulthood, differentiation of diverse cell types
      is controlled by specific genetic and molecular programs for which transcription
      factors are master regulators of gene expression. Here, we present an overview of
      the role of nuclear receptors and their selective pharmacological modulators in
      oligodendrocytes linage, their role in myelination and remyelination and their
      potential use as a therapeutic strategy for demyelinating diseases. We discuss
      several aspects of nuclear receptors including: (1) the biochemistry of nuclear
      receptors superfamily; (2) their role on stem cells physiology, focusing in
      differentiation and cell removal; (3) the role of nuclear receptor in the
      oligodendrocytes cell linage, from oligodendrocyte progenitors cells to mature
      myelinating cells; and (4) the therapeutics opportunities of nuclear receptors
      for specific demyelinating diseases.

PMID- 27714696
TI  - The Role of Galectin-3: From Oligodendroglial Differentiation and Myelination to
      Demyelination and Remyelination Processes in a Cuprizone-Induced Demyelination
      Model.
AB  - The aim of this work was to combine our previously published results with our new
      data to show how galectin-3 (Gal-3) controls myelin integrity and function,
      promotes oligodendroglial cell differentiation, and regulates microglial
      responses to limit cuprizone- (CPZ)-induced demyelination and foster
      remyelination. In this study, 8-week-old Gal-3-deficient (Lgals3 -/-) and wild
      type (WT) mice were fed a diet containing 0.2 % CPZ w/w for 6 weeks, after which
      CPZ was withdrawn in order to allow remyelination. Our results show that
      remyelination was less efficient in Lgals3 -/- than in WT mice. Electron
      microscopic images from remyelinated sections in Lgals3 -/- mice revealed
      collapsed axons with a defective myelin wrap, while remyelinated WT mice had
      normal axons without relevant myelin wrap disruption. MMP-3 expression increased
      during remyelination in WT but not in Lgals3 -/- mice. The number of CD45+,
      TNFalpha+ and TREM-2b+ cells decreased only in WT mice only, with no alterations
      in Lgals3 -/- mice during demyelination and remyelination. Therefore, Gal-3
      influences remyelination by mechanisms involving the tuning of microglial cells,
      modulation of MMP activity, and changes in myelin architecture.

PMID- 27714697
TI  - Prenatal Systemic Hypoxia-Ischemia and Oligodendroglia Loss in Cerebellum.
AB  - Hypoxic-ischemic (HI) injury is an important cause of death and disabilities.
      Despite all improvements in neonatal care, the number of children who suffer some
      kind of injury during birth has remained stable in the last decade. A great
      number of studies have shown alterations in neural cells and many animal models
      have been proposed in the last 5 decades. Robinson et al. (2005) proposed an HI
      model in which the uterine arteries are temporarily clamped on the 18th gestation
      day. The findings were quite similar to the ones observed in postmortem studies.
      The white matter is clearly damaged, and a great amount of astrogliosis takes
      place both in the gray and white matters. Motor changes were also found but no
      data regarding the cerebellum, an important structure related to motor
      performance, was presented. Using this model, we have shown an increased level of
      iNOS at P0 and microgliosis and astrogliosis at P9, and astrogliosis at P23 (up
      to 4 weeks from the insult). NO is important in migration, maturation, and
      synaptic plasticity, but in exacerbated levels it may also contribute to cellular
      and tissue damage. We have also evaluated oligodendroglia development in the
      cerebellum. At P9 in HI animals, we found a decrease in the number of PDGFRalpha+
      cells and an apparent delay in myelination, suggesting a failure in
      oligodendroglial progenitors migration/maturation and/or in the myelination
      process. These results point to an injury in cerebellar development that might
      help to explain the motor problems in HI.

PMID- 27714698
TI  - Acceptability of Mini-Tablets in Young Children: Results from Three Prospective
      Cross-over Studies.
AB  - To ensure optimal, reliable treatment, it is necessary to investigate the
      efficacy, safety and the optimal dose of drug substances and to develop suitable
      age-specific pharmaceutical formulations for the different paediatric age groups
      due to a lack of evidence-based therapeutic options for children. While WHO
      recommends the use of solid dosage forms in general, European Medicines Agency
      (EMA) requires evidence for the suitability of these dosage forms in the targeted
      age group. This review aims to summarize and discuss the data obtained in
      acceptability studies on the suitability of coated and uncoated mini-tablets in
      children of different ages in comparison to a sweet syrup considered as gold
      standard. The predefined outcome parameters 'acceptability' and 'capability to
      swallow' of the two different mini-tablet formulations (uncoated and film-coated)
      were statistically significantly higher than that of the syrup.

PMID- 27714699
TI  - Accelerated Stability Modeling for Peptides: a Case Study with Bacitracin.
AB  - The Accelerated Stability Assessment Program (ASAP) was applied for the first
      time to a peptide, the antibiotic active pharmaceutical ingredient bacitracin.
      Bacitracin and its complex with zinc were exposed to temperature and relative
      humidity conditions from 50 to 80 degrees C and from 0 to 63% for up to 21 days.
      High-performance liquid chromatography was used to analyze the stressed samples
      for both degradant formation and loss of the active (bacitracin A) and two
      inactive isoforms, with identities confirmed by mass spectrometry. These data
      were then analyzed using a humidity-corrected Arrhenius equation and
      isoconversion approach to create a shelf-life predicting model for typical
      storage conditions. Model fitting was found to be good with low residuals in both
      temperature and relative humidity axes for all parameters examined. The generated
      model's predictions for both the native and zinc complex of bacitracin for both
      formation of the major degradation product (F) and loss of the active isoform (A)
      were consistent with longer-term measured values at 30 degrees C/53%RH and 40
      degrees C/75%RH, validating this approach for accelerating the determination of
      long-term stability of a peptide.

PMID- 27714700
TI  - Assessment Methodology for Process Validation Lifecycle Stage 3A.
AB  - The paper introduces evaluation methodologies and associated statistical
      approaches for process validation lifecycle Stage 3A. The assessment tools
      proposed can be applied to newly developed and launched small molecule as well as
      bio-pharma products, where substantial process and product knowledge has been
      gathered. The following elements may be included in Stage 3A: number of 3A batch
      determination; evaluation of critical material attributes, critical process
      parameters, critical quality attributes; in vivo in vitro correlation; estimation
      of inherent process variability (IPV) and PaCS index; process capability and
      quality dashboard (PCQd); and enhanced control strategy. US FDA guidance on
      Process Validation: General Principles and Practices, January 2011 encourages
      applying previous credible experience with suitably similar products and
      processes. A complete Stage 3A evaluation is a valuable resource for product
      development and future risk mitigation of similar products and processes.
      Elements of 3A assessment were developed to address industry and regulatory
      guidance requirements. The conclusions made provide sufficient information to
      make a scientific and risk-based decision on product robustness.

PMID- 27714701
TI  - Comparison of Nanoemulsion and Aqueous Micelle Systems of Paliperidone for
      Intranasal Delivery.
AB  - The objective of the study was to develop and compare the efficiency of
      nanoemulsion and aqueous micelle system of Paliperidone on intranasal
      administration. Both the formulations were evaluated for physical parameters such
      as globule size, pH, viscosity, conductivity and in vitro drug release studies.
      The reduction in spontaneous motor activity of L-dopa and Carbidopa-treated Swiss
      Albino mice on intranasal administration of nanoemulsion and micellar system of
      Paliperidone was compared with plain drug suspension. Histopathological
      evaluation of formulation treated nasal mucosal membrane was performed. Nasal
      spray device was evaluated for spray pattern and volume per actuation. Globule
      size of micellar system and nanoemulsion was found to be 16.14 & 38.25 nm,
      respectively. In vitro release of drug from micellar system was found to be 1.8
      fold higher than nanoemulsion. The loading of drug in nanoemulsion was found to
      be superior (2.5 mg/mL) when compared to micellar system (0.41 mg/mL). The spray
      pattern of micellar system and nanoemulsion from the device was elliptical and
      circular, respectively. The locomotor activity of L-dopa and Carbidopa-treated
      Swiss albino mice was found to be 1096.5+/-78.49, 551.5+/-13.43 and 535.5+/-24.75
      counts/min in case of plain drug suspension, micellar system and nanoemulsion,
      respectively. The intranasal administration of developed formulations showed
      significant difference (p<0.01) in the locomotor activity when compared to
      intranasal administration of plain drug. Thus it can be concluded that both the
      developed formulations have shown improved in vivo activity on intranasal
      administration and pose great potential for delivery of Paliperidone through
      intranasal route.

PMID- 27714702
TI  - Amorphous-based controlled-release gliclazide matrix system.
AB  - The aim of this study was to develop a hydrophilic oral controlled release system
      (CRS) using the amorphous form of gliclazide, a BCS class II compound, listed on
      the WHO list of essential medicines. For this purpose, spray-dried dispersions
      (SDDs) of gliclazide were produced using various grades of hydroxypropyl
      methylcellulose acetate succinate (HPMCAS) or copovidone as carrier under fully
      automated conditions. The solid-state properties of prepared SDDs were
      characterized using X-ray powder diffraction (XRPD), scanning electron microscopy
      (SEM), modulated differential scanning calorimetry (MDSC), and Fourier transform
      infrared spectroscopy (FTIR). Supersaturated micro-dissolution testing of SDDs in
      fasted state-simulated intestinal fluid showed prolonged supersaturation state,
      with solubility increases of 1.5- to 4.0-fold. Solubility and stability
      characteristics of the most desirable SDDs in terms of relative dissolution area
      under the curves (AUCs) (AUC(SDD)/AUC(crystalline)) and stable supersaturated
      state concentration ratio up to 180 min (C180/Cmax) were determined. The
      optimized gliclazide-SDD amorphous forms were included into matrix tablets with
      HPMC blends using compaction simulator. Developed matrix systems were subjected
      to standard USP dissolution testing. Dissolution profiles obtained were linear
      with different slopes indicating varying rates of dissolution. Six-month storage
      stability testing was performed, and dissolution profiles remained stable with
      "similarity factor" (f 2 = 85). Results show that the use of various HPMCAS as a
      drug carrier in the spray-drying process produces homogeneous single-phase SDDs
      which are stable and promising for inclusion into HPMC-based hydrophilic matrix
      systems.

PMID- 27714704
TI  - Development and evaluation of enzyme-linked immunosorbent assay of nucleic acid
      sequence-based amplification for diagnosis of invasive aspergillosis.
AB  - Invasive aspergillosis (IA) is a life-threatening infection in immunocompromised
      patients, rapid and sensitive detection of Aspergillus from clinical samples has
      been a major challenge in the early diagnosis of IA. An enzyme-linked
      immunosorbent assay of nucleic acid sequence-based amplification (NASBA-ELISA)
      was developed to fulfil the need for the efficient diagnosis of these infections.
      The primers targeting 18S rRNA were selected for the amplification of Aspergillus
      RNA by the isothermal digoxigenin (DIG)-labeling NASBA process. The DIG-labeled
      RNA amplicons were hybridized with a specific biotinylated DNA probe immobilized
      on streptavidin-coated microtiter plate. The hybrids were colorimetrically
      detected by the addition of an anti-DIG antibodies linked to ALP and substrate
      (disodium 4-nitrophenyl phosphate). The detection limit of the Aspergillus NABSA
      ELISA system was 1 CFU and the RNA in non-target bacteria or fungus was not
      amplified. The performance of this NASBA-ELISA compared to RT-PCR and
      galactomannan (GM) was evaluated by testing blood samples from 86 patients at
      high risk for IA. The sensitivity of NASBA-ELISA, RT-PCR and GM-ELISA was 80.56 %
      (95 % CI 63.98-91.81), 72.22 % (95 % CI 54.81-85.80), 58.33 % (95 % CI 40.76
      74.49), respectively, and the specificity was 80.00 % (95 % CI 66.28-89.97),
      84.00 % (95 % CI 70.89-92.83), 82.00 % (95 % CI 68.56-91.42). The efficiency of
      the three methods in various combinations was also evaluated. Combination of
      NASBA-ELISA and GM-ELISA testing achieved perfect specificity (100 %; 95 % CI
      92.89-100) and perfect positive predictive value (100 %; 95 % CI 83.16-100). The
      best sensitivity (97.22 %; 95 % CI 85.47-99.93) and the highest Youden index
      (0.652) were obtained by testing with both NASBA and RT-PCR in parallel. In
      conclusion, the NASBA-ELISA assay consists of an alternative process for large
      scale samples detection with semi-quantitative results and provides good clinical
      performance without resorting to expensive equipment. This assay makes it
      possible for the NASBA based RNA diagnosis to become a routine work in
      laboratories in less developed countries with fewer resources.

PMID- 27714703
TI  - Sustained delivery of recombinant human bone morphogenetic protein-2 from
      perlecan domain I - functionalized electrospun poly (epsilon-caprolactone)
      scaffolds for bone regeneration.
AB  - BACKGROUND: Biomaterial scaffolds that deliver growth factors such as recombinant
      human bone morphogenetic proteins-2 (rhBMP-2) have improved clinical bone tissue
      engineering by enhancing bone tissue regeneration. This approach could be further
      improved if the controlled delivery of bioactive rhBMP-2 were sustained
      throughout the duration of osteogenesis from fibrous scaffolds that provide
      control over dose and bioactivity of rhBMP-2. In nature, heparan sulfate attached
      to core proteoglycans serves as the co-receptor that delivers growth factors to
      support tissue morphogenesis. METHODS: To mimic this behavior, we conjugated
      heparan sulfate decorated recombinant domain I of perlecan/HSPG2 onto an
      electrospun poly(epsilon-caprolactone) (PCL) scaffold, hypothesizing that the
      heparan sulfate chains will enhance rhBMP-2 loading onto the scaffold and
      preserve delivered rhBMP-2 bioactivity. RESULTS: In this study, we demonstrated
      that covalently conjugated perlecan domain I increased loading capacity of rhBMP
      2 onto PCL scaffolds when compared to control unconjugated scaffolds.
      Additionally, rhBMP-2 released from the modified scaffolds enhanced alkaline
      phosphatase activity in W20-17 mouse bone marrow stromal cells, indicating the
      preservation of rhBMP-2 bioactivity indicative of osteogenesis. CONCLUSIONS: We
      conclude that this platform provides a sophisticated and efficient approach to
      deliver bioactive rhBMP-2 for bone tissue regeneration applications.

PMID- 27714705
TI  - Predictive factors of bleeding events in adults undergoing extracorporeal
      membrane oxygenation.
AB  - BACKGROUND: Bleeding is the most frequent complication associated with
      extracorporeal membrane oxygenation (ECMO) support in critically ill patients.
      Nonetheless, risk factors for bleeding have been poorly described especially
      those associated with coagulation anomalies and anticoagulant therapy during ECMO
      support. The aim of this study is to describe bleeding complications in
      critically ill patients undergoing ECMO and to identify risk factors for bleeding
      events. METHODS: We retrospectively analysed ICU charts of adults who received
      either veno-venous (VV) or veno-arterial (VA) ECMO support in two participating
      ICUs between 2010 and 2013. Characteristics of patients with and without bleeding
      complications, as per the Extracorporeal Life Support Organisation (ELSO)
      definition, were compared, and the impact of bleeding complications on patient
      outcomes was assessed using survival analysis. Variables that were independently
      associated with bleeding, including daily clinical and biological variables
      during ECMO courses, were modelled. RESULTS: Of the 149 ECMO episodes (111 VA
      ECMO and 38 VV ECMO) performed in 147 adults, 89 episodes (60 %) were complicated
      by at least one bleeding event. The most common bleeding sources were: ECMO
      cannula (37 %), haemothorax or cardiac tamponade (17 %) and ear-nose and throat
      (16 %). Intra-cranial haemorrhage occurred in five (2.2 %) patients. Bleeding
      complications were independently associated with worse survival [adjusted hazard
      ratio (HR) 2.17, 95 % confidence interval (CI) 1.07-4.41, P = 0.03]. Higher
      activated partial thromboplastin time (aPTT) [adjusted odds ratio (OR) 3.00, 95 %
      CI 1.64-5.47, P < 0.01], APACHE III score [adjusted OR 1.01, 95 % CI 1.01-1.02, P
      = 0.01] and ECMO following surgery [adjusted OR 3.04, 95 % CI 1.62-5.69, P <
      0.01] were independently associated with greater risk of bleeding occurrence. A
      similar association between bleeding and higher aPTT was found when non-post
      surgical VA ECMO was considered separately. CONCLUSIONS: Bleeding events based on
      the ELSO bleeding definition occurred in more than 60 % of ECMO episodes and were
      associated with hospital mortality. We identified higher aPTT prior bleeding as
      an independent risk factor for bleeding event, suggesting that better control of
      the aPTT (through a better control of either coagulopathy or anticoagulation) may
      improve patients' outcome.

PMID- 27714706
TI  - What's new in multidrug-resistant pathogens in the ICU?
AB  - Over the last several decades, antibacterial drug use has become widespread with
      their misuse being an ever-increasing phenomenon. Consequently, antibacterial
      drugs have become less effective or even ineffective, resulting in a global
      health security emergency. The prevalence of multidrug-resistant organisms
      (MDROs) varies widely among regions and countries. The primary aim of antibiotic
      stewardship programs is to supervise the three most influential factors
      contributing to the development and transmission of MDROs, namely: (1)
      appropriate antibiotic prescribing; (2) early detection and prevention of cross
      colonization of MDROs; and (3) elimination of reservoirs. In the future, it is
      expected that a number of countries will experience a rise in MDROs. These
      infections will be associated with a high consumption of healthcare resources
      manifested by a prolonged hospital stay and high mortality. As a counteractive
      strategy, minimization of broad-spectrum antibiotic use and prompt antibiotic
      administration will aid in reduction of antibiotic resistance. Innovative
      management approaches include development and implementation of rapid diagnostic
      tests that will help in both shortening the duration of therapy and allowing
      early targeted therapy. The institution of more accessible therapeutic drug
      monitoring will help to optimize drug administration and support a patient
      specific approach. Areas where further research is required are investigation
      into the heterogeneity of critically ill patients and the need for new
      antibacterial drug development.

PMID- 27714709
TI  - The role of the pharmacist in the care of patients with cardiovascular diseases.

PMID- 27714710
TI  - Cardiac manifestations in antineutrophil cytoplasmic autoantibody (ANCA) -
      associated vasculitides.

PMID- 27714708
TI  - Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase
      in HER2+ breast cancer.
AB  - Fatty acid synthase (FASN) is a key lipogenic enzyme for de novo fatty acid
      biosynthesis and a druggable metabolic oncoprotein that is activated in most
      human cancers. We evaluated whether the HER2-driven lipogenic phenotype might
      represent a biomarker for sensitivity to pharmacological FASN blockade. A
      majority of clinically HER2-positive tumors were scored as FASN overexpressors in
      a series of almost 200 patients with invasive breast carcinoma. Re-classification
      of HER2-positive breast tumors based on FASN gene expression predicted a
      significantly inferior relapse-free and distant metastasis-free survival in
      HER2+/FASN+ patients. Notably, non-tumorigenic MCF10A breast epithelial cells
      engineered to overexpress HER2 upregulated FASN gene expression, and the FASN
      inhibitor C75 abolished HER2-induced anchorage-independent growth and survival.
      Furthermore, in the presence of high concentrations of C75, HER2-negative MCF-7
      breast cancer cells overexpressing HER2 (MCF-7/HER2) had significantly higher
      levels of apoptosis than HER2-negative cells. Finally, C75 at non-cytotoxic
      concentrations significantly reduced the capacity of MCF-7/HER2 cells to form
      mammospheres, an in vitro indicator of cancer stem-like cells. Collectively, our
      findings strongly suggest that the HER2-FASN lipogenic axis delineates a group of
      breast cancer patients that might benefit from treatment with therapeutic
      regimens containing FASN inhibitors.

PMID- 27714711
TI  - Denervation of the renal arteries - what next?

PMID- 27714707
TI  - Performance of the PEdiatric Logistic Organ Dysfunction-2 score in critically ill
      children requiring plasma transfusions.
AB  - BACKGROUND: Organ dysfunction scores, based on physiological parameters, have
      been created to describe organ failure. In a general pediatric intensive care
      unit (PICU) population, the PEdiatric Logistic Organ Dysfunction-2 score (PELOD
      2) score had both a good discrimination and calibration, allowing to describe the
      clinical outcome of critically ill children throughout their stay. This score is
      increasingly used in clinical trials in specific subpopulation. Our objective was
      to assess the performance of the PELOD-2 score in a subpopulation of critically
      ill children requiring plasma transfusions. METHODS: This was an ancillary study
      of a prospective observational study on plasma transfusions over a 6-week period,
      in 101 PICUs in 21 countries. All critically ill children who received at least
      one plasma transfusion during the observation period were included. PELOD-2
      scores were measured on days 1, 2, 5, 8, and 12 after plasma transfusion.
      Performance of the score was assessed by the determination of the discrimination
      (area under the ROC curve: AUC) and the calibration (Hosmer-Lemeshow test).
      RESULTS: Four hundred and forty-three patients were enrolled in the study (median
      age and weight: 1 year and 9.1 kg, respectively). Observed mortality rate was
      26.9 % (119/443). For PELOD-2 on day 1, the AUC was 0.76 (95 % CI 0.71-0.81) and
      the Hosmer-Lemeshow test was p = 0.76. The serial evaluation of the changes in
      the daily PELOD-2 scores from day 1 demonstrated a significant association with
      death, adjusted for the PELOD-2 score on day 1. CONCLUSIONS: In a subpopulation
      of critically ill children requiring plasma transfusion, the PELOD-2 score has a
      lower but acceptable discrimination than in an entire population. This score
      should therefore be used cautiously in this specific subpopulation.

PMID- 27714712
TI  - Transapical off-pump mitral valve repair. First experience with the NeoChord
      system in Poland (report of two cases).
AB  - BACKGROUND: Artificial chord implantation to repair a flail or prolapsing mitral
      valve leaflet requires open heart surgery and cardiopulmonary bypass. AIM:
      Transapical off-pump artificial chordae implantation is a new surgical technique
      proposed to treat degenerative mitral valve regurgitation. The procedure is
      performed using the NeoChord DS1000 system (NeoChord, Inc., St. Louis Park, MN,
      USA), which facilitates both implantation and lenght adjustment of the artificial
      chordae under two (2D)- and three (3D)-dimensional transoesophageal
      echocardiographic (TEE) guidance on a beating heart. METHODS: Two male patients
      aged 60 and 55 years with severe mitral regurgitation due to posterior leaflet
      prolapse underwent transapical off-pump artificial chordae implantation on
      September 3, 2015. The procedure was performed by left minithoracotomy under
      general anaesthesia in a cardiac surgical theatre, using 2D and 3D TEE guidance.
      RESULTS: Early procedural success as confirmed by 3D TEE was achieved in both
      patients, with implantation of 6 artificial chordae in the first patient and 3
      artificial chordae in the second patient. Both procedures were uneventful, and no
      postoperative complications were noted. The patients were discharged home on the
      8th and 6th postoperative day, respectively. CONCLUSIONS: The NeoChord DS1000
      system allows both implantation and lenght adjustment of artificial chordae under
      2D and 3D TEE guidance on a beating heart. Our initial experience in 2 patients
      with posterior mitral leaflet prolapse indicates that the procedure is feasible
      and safe.

PMID- 27714713
TI  - Long-term prognosis is related to mid-term changes of glucometabolic status in
      patients with acute myocardial infarction treated invasively.
AB  - BACKGROUND: Glucometabolic status (GS) in patients with acute myocardial
      infarction (AMI) has an impact on prognosis, but it may change over time. AIM: To
      evaluate the prognosis after AMI treated invasively with respect to changes in GS
      assessed by oral glucose tolerance test at discharge and at mid-term follow-up
      visit (FU-visit). METHODS: Glucometabolic status was assessed by two-hour post
      load glycaemia and defined as abnormal glucose tolerance (AGT) or normal glucose
      tolerance (NGT). Out of 454 in-hospital AMI survivors, 368 (81%) patients
      completed an FU-visit and were divided into four groups with respect to GS at
      discharge and FU-visit: group 1 - AGT at discharge and FU-visit (n = 101); group
      2 - AGT at discharge and NGT at FU-visit (n = 48); group 3 - NGT at discharge and
      AGT at FU-visit (n = 114); and group 4 - NGT at discharge and FU-visit (n = 105).
      All-cause mortality was compared between groups with log-rank test. RESULTS:
      Median time from AMI to FU-visit was seven months. Median remote follow-up
      duration after AMI was 31 months. Two-hour post load glycaemia was significantly
      higher in patients with confirmed AGT at FU-visit than in other groups. Mortality
      was higher in group 1 (11.9%) than in group 2 (2.1%; p = 0.034) and group 4
      (2.9%; p = 0.009). Mortality rates between group 2 and 4 were similar (2.1% vs.
      2.9%; p = 0.781). There was no significant difference in mortality between group
      1 and group 3 (11.9% vs. 6.1%; p = 0.114). Mortality in group 3 was over two-fold
      higher than in group 4; however, this difference was statistically non
      significant (6.1% vs. 2.9%; p = 0.247). CONCLUSIONS: Prognosis for patients with
      confirmed AGT was unfavourable; however, patients with AGT at discharge, in whom
      GS improved, had similar mortality to subjects with persistent NGT. The major
      clinical implication from this study is the finding that reassessment of GS by
      repeated oral glucose tolerance test has significant prognostic value and makes
      initial risk stratification performed at discharge more reliable.

PMID- 27714714
TI  - Evaluation of mean platelet volume and platelet distribution width in patients
      with asymptomatic intermediate carotid artery plaque.
AB  - BACKGROUND: Platelets play a significant role in the pathogenesis of
      atherosclerosis. In atherosclerotic plaques, the risk of plaque rupture is more
      crucial than the severity of the stenosis they cause. Non-calcified carotid
      artery plaques are more unstable than calcified plaques, and they are associated
      with a higher risk of rupture, thromboembolism, and consequently, stroke. AIM:
      The purpose of the present study is to compare calcified and non-calcified
      plaques that cause intermediate carotid artery stenosis, with respect to mean
      platelet volume (MPV) and platelet distribution width (PDW). METHODS: A total of
      139 asymptomatic patients with 50-70% stenosis of the carotid artery were
      included in this study. Carotid Doppler ultrasound imaging and computed
      tomography angiography were performed to divide the carotid artery plaques into
      two groups as calcified and non-calcified. Patients included in the calcified (n
      = 73) and non-calcified (n = 66) plaque groups were compared with respect to MPV
      and PDW. RESULTS: Mean platelet volume was statistically significantly higher in
      the non-calcified plaque group compared to the cal-cified plaque group (MPV in
      non-calcified/calcified plaque groups [fL]: 10.0/9.0, respectively) (p < 0.01).
      PDW was not significantly different between the two groups (p = 0.09). Platelet
      count was statistically significantly higher in the calcified plaque group
      compared to the non-calcified plaque group (platelet count in calcified/non
      calcified plaque groups [103/mm3]: 250 +/- 63/226 +/- 56, respectively) (p =
      0.019). Multivariate regression analysis showed that MPV was independently associ
      ated with non-calcified carotid artery plaque (odds ratio 5.95, 95% confidence
      interval 2.63-13.45, p < 0.001). CONCLUSIONS: Mean platelet volume is increased
      in the presence of non-calcified carotid artery plaques that cause asymp-tomatic
      intermediate stenosis. Increased MPV can be used as a marker to predict the risk
      of rupture of the non-calcified carotid artery plaques.

PMID- 27714715
TI  - Total coronary occlusion of infarct-related arteries in patients with non-ST
      elevation myocardial infarction undergoing percutaneous coronary
      revascularisation.
AB  - BACKGROUND: The prevalence and impact of total coronary occlusion of an infarct
      related artery (IRA) on outcomes in patients with non-ST-elevation myocardial
      infarction (NSTEMI) remain unclear. AIM: We evaluated the clinical significance
      of total coronary occlusion in NSTEMI patients. METHODS: A total of 2767 patients
      with NSTEMI enrolled in the Polish Registry of Acute Coronary Syndromes, who
      underwent percutaneous coronary interventions, were analysed. The patients were
      divided into two groups according to preprocedural culprit vessel thrombolysis in
      myocardial infarction (TIMI) flows (TIMI flow 0 - total coronary occlusion [TO]:
      728, 26.3% of the patients, and TIMI flow 1-3 - non-total occlusion [non-TO]:
      2039, 73.7% of the patients). RESULTS: Patients with total occlusion were
      younger, were more often current smokers, and had lower incidence of hypertension
      and diabetes mellitus. The left circumflex artery (LCx) was the major IRA in the
      TO group (48.1%), whereas the left anterior descending artery (LAD) was more
      commonly the IRA in the non-TO group (38.8%). Multivariate analysis revealed that
      LCx as the culprit lesion (OR +/- 95 CI 1.54 [1.26-1.89], p < 0.0001) was an
      independent predictor of TIMI flow 0 in IRA. In-hospital and one-month mortality
      occurred more frequently in the TO group (4.0% vs. 1.7%, p = 0.0005 and 5.5% vs.
      3.5%, p = 0.0175, respectively), no differences in the 12-, 24-, or 36-month
      mortalities were observed between these groups. CONCLUSIONS: Only LCx as a
      culprit lesion was an independent predictor of total occlusion in IRAs. The
      NSTEMI patients with TO had higher in-hospital and one-month mortalities, but
      their long-term outcomes were similar to those of non-TO patients.

PMID- 27714716
TI  - Exercise-induced changes in left ventricular global longitudinal strain in
      asymptomatic severe aortic stenosis.
AB  - BACKGROUND: The management of patients with asymptomatic severe aortic stenosis
      (ASAS) is still under discussion. Therefore, it is advisable to search for the
      parameters of early damage to left ventricular (LV) function. AIM: The aim of the
      study was to assess exercise-induced changes in LV global longitudinal strain
      (GLS) in ASAS. METHODS: The ASAS group consisted of 50 patients (26 women and 24
      men, aged 38.4 +/- 18.1 years) meeting the echocardiographic criteria of severe
      aortic stenosis (AVA < 1 cm2, AVAI < 0.6 cm2/m2, Vmax > 4 m/s, mean aortic
      gradient > 40 mm Hg), with normal LV ejection fraction (LVEF >= 55%) and sinus
      rhythm on electrocardiogram, and without significant concomitant valvular heart
      diseases. The control group consisted of 21 people matched for age and sex.
      Echocardiographic examinations and echocardiographic stress tests with the
      assessment of GLS using the speckle tracking imaging were performed. RESULTS: The
      ASAS group was characterised by statistically significantly higher LV mass index
      (LVMI) and higher LVEF. GLS values at rest in both groups were within normal
      limits but were significantly higher in the control group (-18.9 +/- 2.4% vs. 
      20.7 +/- 1.7%, p = 0.006). An increase in GLS at peak exercise in both groups was
      observed, lower in the ASAS group (the difference was not statistically
      significant: -0.8 +/- 3.0% vs. -2.2 +/- 3.1%, p = 0.086). Changes in GLS during
      exercise (DeltaGLS) did not correlate with the parameters of the severity of
      aortic stenosis. In the multivariate model, LVMI proved to be a factor associated
      with GLS at rest and during exercise. CONCLUSIONS: In patients with ASAS, GLS is
      a non-invasive marker of an early stage of LV myocardial damage associated with
      myocardial hypertrophy. An increase in GLS during exercise in the ASAS group,
      smaller than in the control group, indicates a preserved functional reserve of
      the LV myocardium but smaller than in healthy individuals. The assessment of the
      clinical usefulness of exercise-induced changes in GLS requires further research.

PMID- 27714717
TI  - Annual prognostic factors in chronic heart failure in patients over 80 years old.
AB  - BACKGROUND: In the elderly the most common cause of hospitalisation and the
      leading cause of death is heart failure (HF). AIM: The purpose was to determine
      prognostic factors in chronic HF (CHF) in octogenarians and nonagenarians.
      METHODS: The analysis included 197 consecutive patients over 80 years old (mean
      age 83.63 +/- 3.01 years; 46.19% men) hospitalised in 2010-2013 due to CHF. Sixty
      two parameters were investigated, such as: age, gender, New York Heart Asso
      ciation functional class, body mass index, blood pressure, other comorbidities,
      the parameters of the 12-lead resting electro-cardiography and the
      echocardiography, the results of basic laboratory tests, and selected biomarkers,
      including N-terminal pro-B-type natriuretic peptide, high-sensitive troponin T
      (hs-TnT), and high-sensitive C-reactive protein. Participants remained in a
      prospective follow-up for 12 months. We defined the primary endpoint as death due
      to cardiovascular causes and the composite endpoint, which consisted of: death
      due to cardiovascular causes and/or hospitalisation for exacerbation of CHF.
      Follow-up concerning the deaths was performed in 189 patients, composite endpoint
      in 168 and hospitalisation in 166. The uni- and multivariate logistic regression
      stepwise analysis was performed for the entire population, according to left
      ventricular ejection fraction (LVEF < 45% and >= 45%) and in the group with
      glomerular filtration rate (GFR) < 60 mL/min. RESULTS: Patients who died
      constituted 11.1% of the study population (21/189). In multivariate analysis four
      variables were independently associated with the primary endpoint: GFR (OR =
      0.92), hypertension (OR = 0.19), lung diseases (OR = 9.36), and vascular diseases
      (OR = 6.07). In turn, in the group of patients who reached the composite endpoint
      (55/168; 32.7%), the only statistically significant independent variable was
      anaemia (OR = 4.71). In the subpopulation of patients with LVEF < 45% the
      prognostics for each endpoint were vascular diseases and lung diseases, and they
      increased the risk from 10- to 24-fold. In the subgroup of patients with LVEF >=
      45% the independent variable associated with the composite endpoint was
      haemoglobin (OR = 0.61), in turn for death the prognostics were: white blood cell
      count, hs-TnT, and vascular diseases (respectively OR = 1.30; OR = 1.04; OR =
      3.96). In the population with GFR < 60 mL/min variables with prognostic
      importance for the composite endpoint were red blood cell parameters: red blood
      cell distribution width (OR = 1.42) and anaemia (OR = 3.79), while for occurrence
      of death they were the same as for the entire population - vascular (OR = 5.16)
      and lung diseases (OR = 4.72). CONCLUSIONS: In patients over 80 years old with
      CHF, comorbidities are of important prognostic value for annual prognosis. The
      most aggravating factor in studied subgroups was lung disease.

PMID- 27714718
TI  - The efficacy and safety of valsartan and combination of valsartan and
      hydrochlorothiazide in the treatment of patients with mild to moderate arterial
      hypertension - the VICTORY trial.
AB  - BACKGROUND AND AIM: The aim of the trial was to establish the efficacy and safety
      of Valsacor(r) (valsartan) and Valsacombi(r) (combination of valsartan and
      hydrochlorothiazide) in a wide variety of patient populations with mild to
      moderate arterial hypertension. METHODS: We performed an international,
      multicentre, open-label, prospective trial. After one week of washout in
      previously treated patients, the patients were treated for 16 weeks according to
      the protocol. Naive patients entered the treatment period immediately. During the
      active treatment, four visits were planned for each patient to obtain the data
      for the primary and secondary efficacy endpoints analysis. The principal methods
      were blood pressure (BP) measurement, additionally in a subgroup of patients,
      assessment of erectile function. The initial dosage of valsartan 80 mg/day was
      titrated up to 320 mg/day to achieve the BP goal, with the addition of
      hydrochlorothiazide (HCTZ) in a fixed-dose combination (FDC), if needed. RESULTS:
      Mean +/- standard deviation changes from baseline at week 16 were -26.6 +/- 10.4
      mm Hg (systolic BP) and -14.8 +/- 7.6 mm Hg (diastolic BP). A total of 91% of the
      patients treated with either valsartan or valsartan FDC achieved the BP goal.
      Adverse reactions were experienced by 7.1% of the patients, with the most common
      being headache (1.9%), palpitation (1.6%), dizziness (1.6%), and fatigue (1.6%),
      during the whole trial. CONCLUSIONS: The results of the VICTORY trial show that
      valsartan and valsartan FDC effectively reduce the BP in patients with mild to
      moderate arterial hypertension and have a good tolerability profile.

PMID- 27714719
TI  - Platelet distribution width predicts left ventricular dysfunction in patients
      with acute coronary syndromes treated with percutaneous coronary intervention.
AB  - BACKGROUND: The role of platelets in the pathophysiology of acute coronary
      syndromes (ACS) is undeniable, but precise relationships between platelet
      activity and treatment outcomes are a matter of continuant investigation. Among
      platelet indices, mean platelet volume (MPV) has proven to be a valuable
      predicting factor in cardiac patients. However, platelet distribution width (PDW)
      is reported to be a more specific marker of platelet reactivity. Thus,
      application of PDW in risk stratification of ACS treatment is an up-to-date
      subject of research. PDW values in the assessment of left ventricular (LV)
      function have not been previously studied. AIM: The aim of the study was to
      evaluate whether admission PDW can predict LV systolic function in patients with
      ACS treated with stent implantation. METHODS: On-admission PDW was measured in
      278 consecutive patients with diagnosis of ACS, who underwent stent(s)
      implantation. Echocardiogram with LV ejection fraction (LVEF) estimation was
      performed within 24 h of percutaneous coronary intervention. Additionally,
      patients were under one-year follow-up, and one-year all-cause mortality was
      assessed. RESULTS: According to receiver-operating characteristics (ROC)
      analysis, a PDW value greater than 12.8 fL could predict LVEF <= 35% with
      sensitivity of 81% and specificity of 39% (AUC 0.614; p = 0.0177). Only a trend
      was noted in ROC for PDW and one-year mortality (AUC 0.608; p = 0.0815).
      Multivariate logistic regression analysis has shown that the PDW parameter
      correlates independently with both systolic heart failure with LVEF <= 35% (PDW
      cut-off: 12.8 fL, OR 2.8107, CI 1.1401-6.9293, p = 0.0248) and one-year mortality
      (PDW cut-off: 16 fL, OR 2.6750, CI 1.0190-7.0225, p = 0.0457). CONCLUSIONS:
      Admission PDW may serve as a simple and widely available predictor of impaired LV
      function in patients with ACS. Association between PDW and mortality needs to be
      confirmed in larger studies.

PMID- 27714720
TI  - The effect of epicardial adipose tissue thickness on left ventricular diastolic
      functions in patients with normal coronary arteries.
AB  - BACKGROUND AND AIM: The aim of this study is to evaluate the effect of epicardial
      adipose tissue (EAT) thickness on left ventricular diastolic functions in
      patients with normal coronary arteries (NCA) proven by angiography. METHODS: We
      selected study patients who were referred to coronary angiography due to typical
      chest pain or atypical chest pain with a positive pre-test result for coronary
      artery disease (CAD). After coronary angiography, 85 patients with significant
      coronary lesion (>= 50% stenosis) served as the CAD group, 82 patients with non
      significant coronary lesion (< 50% stenosis) and/or a coronary plaque served as
      the non-significant CAD group, and 83 patients with NCA served as the NCA group.
      All patients underwent transthoracic echocardiographic examination to measure EAT
      thickness and left ventricular diastolic properties. RESULTS: Gensini score,
      total cholesterol, and C-reactive protein were significantly higher in the CAD
      group compared to the non-significant CAD group and the NCA group. The average of
      EAT thickness was 7.3 +/- 2.4 mm in all groups. It was 5.8 +/- 2.3 mm in the NCA
      group, 6.4 +/- 2.4 mm in the non-significant CAD group, and 7.8 +/- 2.2 mm in the
      CAD group (p < 0.001). In correlation analyses, average EAT thickness was
      significantly correlated with E/e' ratio in the NCA group. In multivariate
      analysis, average of EAT thickness was significantly associated with left
      ventricular diastolic dysfunction in subjects with NCA (OR 1.019, 95% CI 1.012
      1.027, p < 0.001). CONCLUSIONS: Based on our findings, EAT thickness may have an
      effect on left ventricular diastolic functions. This independent relationship
      showed us the clinical importance of measuring of EAT thickness.

PMID- 27714721
TI  - Basic laboratory parameters as predictors of in-hospital death in patients with
      acute decompensated heart failure: data from a large single-centre cohort.
AB  - BACKGROUND: Heart failure (HF) is a growing cause of hospitalisation worldwide,
      and despite significant progress in its treat-ment it is still associated with
      high mortality. AIM: The aim of this study was to find factors predicting in
      hospital death in acute decompensated HF by analysis of basic laboratory data and
      echocardiography, routinely collected on admission to the hospital. METHODS: To
      this single-centre retrospective study we involved 638 consecutive patients
      hospitalised in the years 2007-2008 due to acute decompensated HF. To the initial
      univariate analysis we included the results of echocardiography and 36 basic
      laboratory tests performed at hospital admission. Parameters significantly
      associated with in-hospital death in univariate analysis were taken to
      multivariate regression analysis. RESULTS: In-hospital death occurred in 119
      cases (median age 75 years; 40.3% females). The multivariate analysis revealed
      sig-nificant association between in-hospital death and: higher leukocyte count
      (death [D]: 13.5 vs. survival [S]: 8.8 G/L, p < 0.01), higher neutrophil count
      (D: 10.5 vs. S: 5.9 G/L, p < 0.01), lower lymphocyte count (D: 1.3 vs. S: 1.7
      G/L, p < 0.05), higher C-reactive protein concentration (D: 20.8 vs. S: 6.7
      mg/dL, p < 0.01), higher serum glucose concentration (D: 167.0 vs. S: 116.0
      mg/dL, p < 0.00001), higher serum creatinine concentration (D: 1.5 vs. S: 1.2
      mg/dL, p < 0.0001), higher blood urea nitrogen concentration (D: 29.0 vs. S: 22.0
      mg/dL, p < 0.00001), and higher aspartate aminotransferase (D: 72.0 vs. S: 27.0
      U/L, p < 0.0001). Surprisingly, there was no significant association with
      echocardiographic parameters. CONCLUSIONS: Analysis of basic laboratory data
      collected on admission to the hospital may help to identify patients with acute
      decompensated HF, who are at high risk of in-hospital death.

PMID- 27714722
TI  - Plasmatic NT-proBNP concentrations in patients with coexistent periodontal
      disease and congestive heart failure: pilot studies.
AB  - BACKGROUND: The presented pilot study was conducted in order to evaluate dynamic
      fluctuations of blood inflammation markers among patients with congestive heart
      failure (CHF) and coexistent periodontitis (PD). AIM: The study hypothesis stated
      that elimination of chronic inflammation caused by PD has a significant impact on
      inflammation markers and, secondarily, also on the course and prognosis of CHF. N
      terminal pro-B-type natriuretic peptide (NT-proBNP) and tumour necrosis factor
      alpha (TNF-alpha) markers were assessed due to their proven diagnostic
      significance. METHODS: Blood samples were collected at the time of CHF patients'
      admission to the clinical ward (I examination) and then after 3-9 months (average
      six months) after periodontal treatment completion (II examination). With
      antibiotic cover, basic periodontal parameters (such as CAL, PD, PI, BOP) were
      evaluated, scaling and root-planning were performed, and orthopantomogram X-rays
      were conducted. Patients received instructions about domestic oral hygiene
      procedures. Measurements were repeated during a second examination of blood
      samples. Obtained results were compared and statistically analysed. RESULTS: The
      initial outcome of the study confirmed the hypothesis that maintaining good and
      complex oral hygiene has an essential impact on blood concentration of NT-proBNP
      and TNF-alpha markers. CONCLUSIONS: Exploration of possibilities considering
      medical help and treatment optimisation seems to be evident also according to
      improvement of prognosis, therapy effectiveness, and patient comfort. Foregoing
      conclusions about biomarkers are, according to authors' best knowledge, the first
      such results reported in medical literature.

PMID- 27714723
TI  - Estimation of shear stress by using a myocardial bridge-mural coronary artery
      simulating device.
AB  - BACKGROUND: This study was aimed at developing a myocardial bridge-mural coronary
      artery simulative device and analyzing the relationship between shear stress on
      the mural coronary artery and atherosclerosis. METHODS: A myocardial bridge-mural
      coronary artery simulative device was used to simulate experiments in vitro. In
      the condition of maintaining any related parameters such as system temperature,
      average flow rate, and heart rate, we calculated and observed changes in proximal
      and distal mean values, and oscillatory value of shear stress on the mural
      coronary artery by regulating the compression level of the myocardial bridge to
      the mural coronary artery. RESULTS: Under 0% compression, no significant
      differences were observed in distal and proximal mean values and oscillatory
      value of the shear stress on the mural coronary artery. With the increase in the
      degree of compression, the mean shear stress at the distal end was greater than
      that at the proximal end, but the oscillatory value of the shear stress at the
      proximal end was greater than that at the distal end. CONCLUSIONS: The
      experimental results of this study indicate that myocardial bridge compression
      leads to abnormal hemodynamics at the proximal end of the mural coronary artery.
      This abnormal phenomenon is of great significance in the study of atherosclerosis
      hemodynamic pathogenesis, which has potential clinical value for pathological
      effects and treatments of myocardial bridge.

PMID- 27714724
TI  - Assessment of cardiovascular function following transcatheter aortic valve
      implantation based on six-minute walk test.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is presently a
      recognized treatment mo-dality for patients with severe aortic stenosis
      ineligible for surgery. It reduces mortality as compared to the conservative
      treatment. It is further expected from this therapy to improve quality of life by
      improving of the cardiovascular function performance. The aim of this study is to
      compare patients' cardiovascular system efficiency in the 6-minute walk test
      (6MWT) made before and after TAVI and at the 6-12-month follow-up. METHODS: From
      January 2009 until February 2012, in the Silesian Center for Heart Diseases in
      Zabrze, TAVI was performed in 104 patients. Eighty-two patients who underwent
      6MWT before surgery were qualified for the analysis. The average age of the
      patients was 76.0 +/- 9.17 years, women made 45.1%. The risk of surgical
      treatment according to the Logistic Euroscore averaged 22.76 +/- 12.63%, and by
      the Society of Thoracic Surgeons - 5.55 +/- 3.34%. The 6MWT was performed within
      1 month before the TAVI procedure, up to a month after the procedure and during
      the 6-12-month follow-up. RESULTS: The 6-minute walk test after TAVI was
      performed by 64 patients, and after 6-12 month follow-up by 46 patients. The
      average distance in 6MWT increased from 268.4 +/- 89.0 m before treat-ment to
      290.0 +/- 98.2 m after the procedure (p = 0.008) and 276.1 +/- 93.5 m to 343.1 +/
      96.7 m after 6-12 months (p < 0.0001). CONCLUSIONS: Transcatheter aortic valve
      implantation procedures significantly improve function of the cardiovascular
      system evaluated by the 6MWT in 1- and 6-12-month observations. (Cardiol J 2017;
      24, 2: 167-175).

PMID- 27714726
TI  - The variable origin of the lateral circumflex femoral artery: a meta-analysis and
      proposal for a new classification system.
AB  - The lateral circumflex femoral artery (LCFA) is responsible for vascularisation
      of the head and neck of the femur, greater trochanter, vastus lateralis and the
      knee. The origin of the LCFA has been reported to vary significantly throughout
      the literature, with numerous branching patterns described and variable distances
      to the mid-inguinal point reported. The aim of this study was to determine the
      estimated population prevalence and pooled means of these anatomical
      characteristics, and review their associated clinical relevance. A search of the
      major electronic databases was performed to identify all articles reporting data
      on the origin of the lateral circumflex femoral artery and its distance to the
      mid-inguinal point. Additionally, an extensive search of the references of all
      relevant articles was performed. All data on origin, branching, and distance to
      mid-inguinal point was extracted and pooled into a meta-analysis. A total of 26
      articles (n = 3731 lower limbs) were included in the meta-analysis. Lateral
      circumflex femoral artery most commonly originates from the deep femoral artery
      with a pooled prevalence of 76.1% (95% confidence interval 69.4-79.3). The deep
      femoral artery-derived lateral circumflex femoral artery was found to originate
      with a mean pooled distance of 51.06 mm (95% confidence interval 44.61-57.51 mm)
      from the mid-inguinal point. Subgroup analysis of both gender and limb side data
      were consistent with these findings. Due to variability in the lateral circumflex
      femoral artery's origin and distance to mid-inguinal point, anatomical knowledge
      is crucial for clinicians to avoid iatrogenic injuries when performing procedures
      in the femoral region, and thus radiographic assessment prior to surgery is
      recommended. Lastly, we propose a new classification system for origin of the
      lateral circumflex femoral artery.

PMID- 27714725
TI  - In vitro assessment of six aspiration catheters using a distal protection filter.
AB  - BACKGROUND: We assessed performance of 6 aspiration catheters for distal
      embolization using a distal protection filter in an in vitro experiment. In acute
      myocardial infarction, a distal protection filter is used for lesions likely to
      induce a distal embolism. Which aspiration cathether is most effective when used
      with a distal protection filter remains still unclear. METHODS: A 0.5-cm3 bolus
      of gelatin as a model of stagnant pools of coronary plaque debris was captured in
      the distal protection filter and aspirated by 6 aspiration catheters. We measured
      and compared the length of the suspended embolus matter. RESULTS: Among the 6
      catheters evaluated, the use of the Export Advance catheter (Medtronic) resulted
      in significantly shorter lengths of the suspended embolus matter compared to the
      use of the TVAC II (Nipro), Thrombuster III SL (Kaneka), and Rebirth Pro
      (Goodman) catheters (p < 0.01). The residual embolus matter in all cases had
      drained distally to the distal protection filter when the filter was retrieved.
      CONCLUSIONS: The use of the Export Advance catheter showed better performance
      using a distal protection filter in this in vitro experiment, and its use might
      be more effective in preventing distal embolisms in combination with a distal
      protection filter.

PMID- 27714727
TI  - Anatomy of the long peroneal muscle of the leg.
AB  - BACKGROUND: The aim of the work was to perform a morphometric analysis of the
      long peroneal muscle (LPM) of the leg and explore the relationship between muscle
      belly and tendon. MATERIALS AND METHODS: Ten lower limbs (8 right and 2 left)
      were fixed in formaldehyde and dissected using standard technique. The LPM was
      exposed from the proximal attachment to the top of a lateral malleolus. RESULTS:
      The tendon was subsequently freed and various measurements were taken. The tendon
      of the LPM enters deep into the muscle belly. Muscle fibres surround the tendon
      and descend as far down as 4 cm above the lateral malleolus. Muscle fibres insert
      mainly along posterior border of the tendon and on its medial surface, leaving
      lateral surface only partly covered. CONCLUSIONS: The LPM contains a long
      intramuscular segment of the tendon and area of the musculotendinous junction
      varies along the LPM. It makes the idea of uniform pennation pattern of the LPM
      unlikely.

PMID- 27714728
TI  - Developmental parallelism in primates.
AB  - The authors examined a large random sample of skulls from two species of
      macaques: rhesus monkeys and cynomolgus monkeys. The skulls were measured,
      divided into age and sex groups and thoroughly analysed using statistical
      methods. The analysis shows that skulls of young rhesuses are considerably more
      domed, i.e. have better-developed neurocrania, than their adult counterparts.
      Male and female skulls, on the other hand, were found to be very similar, which
      means that sexual dimorphism of the rhesus macaque was suppressed. Both of these
      patterns are known from the human evolutionary pattern. No such parallelism to
      the development of Homo sapiens was found in the cynomolgus monkeys. The authors
      conclude that mosaic hominisation trends may have featured in the evolution of
      all primates. This would mean that apes were not a necessary step on the
      evolutionary way leading to the development of Homo sapiens, who may have started
      to evolve at an earlier stage of monkeys.

PMID- 27714729
TI  - What can anthropometric measurements tell us about obstructive sleep apnoea?
AB  - BACKGROUND: Clinical detection of anatomic narrowing of the upper airway may
      facilitate early recognition of obstructive sleep apnoea (OSA). The aim of this
      study was to investigate whether anthropometric measurement can be used to
      predict OSA. MATERIALS AND METHODS: One hundred forty-seven subject were included
      from those patients who were referred to our sleep laboratory with suspected
      sleep apnoea. All patients were divided two groups with respect to the apnoea
      hypopnoea index (AHI). The first group was diagnosed as OSA, AHI greater than 5.
      The second group was not diagnosed with OSA, AHI less than 5 (non-OSA control).
      Anthropometric measurements such as lower face height (LFH), interincisial
      distance, nose height, anterior neck height (ANH), lateral neck height, posterior
      neck height (PNH), ramus mandible height, corpus mandible height (CML), bigonial
      distance (BGD), neck width, and neck depth were assessed. RESULTS: Patients with
      OSA had higher body mass index (BMI) and larger LFH, ANH, thyromental distance,
      CML, BGD, and neck circumference than those without OSA (p < 0.0001, p < 0.0001,
      p < 0.0001, p < 0.0001, p < 0.0001, p = 0.023, p < 0.0001, respectively). There
      was no difference between the two groups in terms of other parameters.
      CONCLUSIONS: In this study, it was determined that BMI, lower face height, neck
      height, mandible length, bigonial width, thyromental distance and neck
      circumference are in significant relationship with sleep disordered breathing.
      Thus, these measurements may be used in clinical practice for prediction of OSA.

PMID- 27714730
TI  - Anatomic assessment of the left main bifurcation and dynamic bifurcation angles
      using computed tomography angiography.
AB  - BACKGROUND: An understanding of the left main coronary artery (LMCA) anatomy is
      important for accurate diagnosis and therapy. We aimed to investigate LMCA
      anatomy via 128-multisliced coronary computed-tomography-angiography (CCTA) in
      patients with normal LMCA. MATERIALS AND METHODS: A total of 201 CCTA studies
      were included in this study. Anatomical features of LMCA including cross
      sectional areas of the LMCA ostial, LMCA distal, left anterior descending artery
      (LAD) ostial and left circumflex artery (LCX) ostial, and degree of tapering and
      LMCA bifurcation angles (BA) in the form of LMCA-LCX BA, LMCA-LAD BA, LAD-LCX BA
      at end-diastole and end-systole. RESULTS: The mean age was 55 +/- 11; 55.7% of
      patients were males. Right coronary artery was dominant in 173 (86.1%) patients.
      Mean LMCA length was 10.0 +/- 4.5 mm. The mean values of LMCA ostial, LMCA
      distal, LAD ostial and LCX ostial areas were 18.2 +/- 5.1 mm2, 13.2 +/- 4.0 mm2,
      9.0 +/- 3.2 mm2 and 7.6 +/- +/- 2.8 mm2, respectively. LMCA ostial-distal area,
      LMCA distal-LAD ostial area and LMCA distal-LCX ostial area ratios were >= 1.44 -
      < 1.69 in 47 (23.4%), 53 (26.4%), 47 (23.4%) patients, respectively, and were >=
      1.69 - < 1.96 in 19 (9.5%), 24 (11.9%), 40 (19.9%) patients respectively.
      Systolic motion modifies LMCA BAs; systolic motion begets an increment of LMCA
      LAD angle in 72.6% of patients and decrement of LAD-LCX angle in 75.6% of
      patients. Patients with T-shaped LAD-LCX BA was shown to have significantly
      longer LMCA, larger LAD ostial area, larger LCX ostial area and higher diastolic
      to-systolic range (DSR) of LAD-LCX BA compared to patients with Y-shaped LAD-LCX
      BA. CONCLUSIONS: LMCA with T-shaped distal BA was found to have significantly
      longer LMCA, larger LAD ostial area, larger LCX ostial area and higher DSR of
      distal BA compared to patients with Y-shaped distal BA. These findings may
      provide useful information for LMCA bifurcation stenting or designing dedicated
      stents for LMCA.

PMID- 27714731
TI  - An anatomical investigation of the carotid canal.
AB  - BACKGROUND: The carotid canal (CC) located in the petrous temporal bone transmits
      the internal carotid artery, internal carotid venous plexus and sympathetic nerve
      plexus from the neck into the cranial cavity. It is an accessible passage into
      the cranial cavity and is considered an important anatomical landmark for
      neurosurgeons. The aim of this study was to investigate the topographical,
      morphometric and morphological parameters of the CC. MATERIALS AND METHODS: An
      examination of the CC and related adjacent structures in 81 dry skull specimens
      was performed. Distribution of sample by sex was 34 females and 47 males, and by
      race 77 African and 4 Caucasian. The mean age was 50 years (range: 14-100 years).
      RESULTS: The external opening of the CC was found to be round-shaped, oval-shaped
      and tear-drop-shaped in 28.4%, 49.4% and 22.2% of the specimens, respectively.
      (1) Mean diameters [mm]: (a) medio-lateral 7.52 mm and (b) antero-posterior
      5.41mm. Statistically significant difference in the vertical diameter was
      recorded in the race groups and laterality of the samples. (2) Mean distances
      [mm] between: (a) medial margins of external opening of CC was 50.03 mm, (b)
      lateral margins of external opening of CC was 62.73 mm and (c) external openings
      of CC and foramen lacerum was 15.6 mm. There was a statistically significant
      correlation between race and location of the opening of external CC in relation
      to foramen lacerum (viz. postero-lateral, lateral and diagonal, and lateral).
      CONCLUSIONS: The present study corroborated previous reports on the CC; however,
      the tear-drop shaped external CC opening was a unique finding. The knowledge of
      the reference measurements pertaining to the CC and its relationship to adjacent
      structures may postulate a suitable surgical "safe-zone" range within the CC
      area.

PMID- 27714732
TI  - Tetrafurcation of the subscapular artery. Anatomical and clinical implications.
AB  - Anatomic variations of axillary artery branches are commonly encountered during
      radiological investigation and surgical operations. Their existence can confuse
      interpretation of radiological results and lead to undesired complications during
      surgery. In this report authors describe a rare case of a subscapular arterial
      trunk that gave origin to thoracodorsal, circumflex scapular, posterior humeral
      circumflex, and lateral thoracic artery. Such a variation might cause undesired
      sequelae during trauma management and a variety of common flap harvesting
      operations including latissimus dorsi, scapular and parascapular flaps.
      Furthermore it presents embryological interest as it gives insight to embryologic
      development of axillary area.

PMID- 27714733
TI  - Enthesopathic patterns of two South African female cadavers.
AB  - Enthesopathy is considered to be an osseous phenomenon, either disease-specific
      or bone-site specific, which occurs at the enthesis of bone. Upon routine
      cadaveric dissection of the glenohumeral region in two Caucasian females,
      enthesopathy of the right proximal humerus was observed unilaterally in both
      cases. Case 1 exhibited an inconsistent pattern of bony protuberances and crests
      dispersed across the lesser and greater tuberosities of the right humeral head.
      Varying degrees of ossification of the distal subscapularis muscle was also
      observed. Case 2 presented with a distinctively large enthesophyte that protruded
      supero-medially from the proximal right humerus. In addition, ossification of the
      distal-most aspect of the supraspinatus muscle was identified. Cases 1 and 2 were
      both reflective of osteophytic enthesopathy as proliferative change was clearly
      visible on the proximal aspect of each humerus. Whilst the presence of
      enthesopathies may be indicative of underlying pathology, it may prove beneficial
      to the field of bioarchaeology for the remodelling of lifestyles of ancient
      civilizations through the provision of current day variations as seen in these
      two case studies.

PMID- 27714734
TI  - Influenza in the Eastern Mediterranean Region: identifying the unknowns for
      detection and control of epidemic and pandemic threats.

PMID- 27714735
TI  - Research agenda on persistent and unpredictable threat of influenza and emerging
      respiratory infections: a public health necessity in the Eastern Mediterranean
      Region.

PMID- 27714736
TI  - Estimation of influenza and severe acute respiratory illness incidence (burden)
      in three provinces of the Islamic Republic of Iran, 2012 and 2013.
AB  - There are few estimates of influenza burden in the WHO Region for the Eastern
      Mediterranean. In this study we estimated the burden of severe acute respiratory
      infection (SARI) and influenza-associated SARI (F-SARI) in selected provinces of
      Islamic Republic of Iran, the trends of SARI and confirmed cases of influenza (F
      SARI) over 12 months (seasonality), and the age groups most at risk. Using the
      electronic Iranian influenza surveillance system and data of cases in sentinel
      hospitals of 3 selected provinces, we estimated the monthly trend (seasonality)
      of incidence for SARI and F-SARI, overall incidence of SARI and F-SARI and their
      disaggregation by age with the aid using the Monte Carlo technique. The age
      groups most at-risk were children aged under 2 years and adults older than 50
      years.

PMID- 27714737
TI  - Characteristics of severe acute respiratory infectionassociated hospitalization
      in Yemen, 2014/15.
AB  - This study aims to describe etiological agents, demographic details of patients,
      seasonality and underlying conditions among patients hospitalized due to viral
      severe acute respiratory infection (SARI) in Yemen. We carried out a
      retrospective descriptive analysis of data from January 2014 to December 2015.
      Nasopharyngeal swabs were taken from each patient for laboratory testing. A total
      of 1346 diagnostic specimens were tested, of which 733 (54%) were positive for
      influenza viruses. Influenza A(H3) and A(H1N1) pdm09 predominated. Respiratory
      syncytial virus (RSV) was reported predominantly among children (41%). Males
      (61%) were more affected than females. The median age was 1 year (range 0.5
      94.0). The median length of hospitalization was 6 days. Chronic cardiovascular
      disease was the most commonly reported underlying condition, but 67% had no
      documented underlying disease. Respiratory viruses, particularly RSV, adenovirus
      and influenza, were commonly associated with hospitalization for SARI.

PMID- 27714738
TI  - Contribution of laboratories in the WHO Eastern Mediterranean Region to the
      selection of candidate seasonal influenza vaccine, 2010-2015.
AB  - The World Health Organization (WHO) formulates recommendations for viruses to be
      included in vaccines for the influenza seasons in the northern and southern
      hemispheres on the basis of analyses by its collaborating centres (CCs). This
      report describes the contribution of influenza laboratories and national
      influenza centres in countries in the WHO Region for the Eastern Mediterranean to
      the selection process of seasonal and pre-pandemic influenza virus subtypes. Data
      submitted by 22 countries to FluNet and FluID between September 2010 and June
      2015 were analysed. National Influenza Centres (NICs) in 12 countries (55%)
      reported data, 5 (23%) to both FluNet and FluID and 7 (32%) only to FluNet. The
      WHO CC in London characterized 78% of the samples, and the CC in Atlanta,
      characterized 21%. The contribution of influenza laboratories and NICs from this
      Region to global influenza surveillance is appreciable. However, enhancing the
      contribution through initiatives such as the Pandemic Influenza Preparedness
      Framework is still needed.

PMID- 27714739
TI  - Detection of influenza B viruses with reduced sensitivity to neuraminidase
      inhibitor in Morocco during 2014/15 season.
AB  - We monitored phenotypic and genotypic susceptibility of influenza viruses
      circulating in Morocco during 2014-2015 to oseltamivir and zanamivir. Throat and
      nasal swab specimens were collected from outpatients (with influenza-like
      illness) and inpatients (with severe acute respiratory illness) and tested for
      influenza viruses using real-time reverse transcription polymerase chain
      reaction. Positive samples were inoculated in MDCK cells and virus phenotypic
      susceptibility to neuraminidase inhibitors (NAIs) was assessed using fluorescent
      NA inhibition. Of 440 specimens, 135 were positive for influenza B Yamagata-like
      virus, 38 were A(H1N1)pdm09 and 25 were A(H3N2). Sixty influenza B viruses
      isolated from MDCK cells showed no significant resistance to NAIs. However, two
      of these strains, B/Morocco/176H/2015 and B/Morocco/CP10/2015, showed reduced
      susceptibility to oseltamivir. The two influenza B viruses with reduced
      susceptibility to oseltamivir show that ongoing NAI susceptibility surveillance
      is essential.

PMID- 27714740
TI  - Modelling of seasonal influenza and estimation of the burden in Tunisia.
AB  - The burden of influenza was estimated from surveillance data in Tunisia using
      epidemiological parameters of transmission with WHO classical tools and
      mathematical modelling. The incidence rates of influenza-associated influenza
      like illness (ILI) per 100 000 were 18 735 in 2012/2013 season; 5536 in 2013/14
      and 12 602 in 2014/15. The estimated proportions of influenza-associated ILI in
      the total outpatient load were 3.16%; 0.86% and 1.98% in the 3 seasons
      respectively. Distribution of influenza viruses among positive patients was:
      A(H3N2) 15.5%; A(H1N1)pdm2009 39.2%; and B virus 45.3% in 2014/2015 season. From
      the estimated numbers of symptomatic cases, we estimated that the critical
      proportions of the population that should be vaccinated were 15%, 4% and 10%
      respectively. Running the model for the different values of R0, we quantified the
      number of symptomatic clinical cases, the clinical attack rates, the symptomatic
      clinical attack rates and the number of deaths. More realistic versions of this
      model and improved estimates of parameters from surveillance data will strengthen
      the estimation of the burden of influenza.

PMID- 27714741
TI  - An outbreak of Middle East Respiratory Syndrome (MERS) due to coronavirus in Al
      Ahssa Region, Saudi Arabia, 2015.
AB  - Between 19 April and 23 June 2015, 52 laboratory-confirmed cases of Middle East
      Respiratory Syndrome due to coronavirus (MERS) were reported from Al-Ahssa
      region, eastern Saudi Arabia. The first seven cases occurred in one family; these
      were followed by 45 cases in three public hospitals. The objectives of this
      investigation were to describe the epidemiological characteristic of the cluster
      and identify potential risk factors and control measures to be instituted to
      prevent further occurrence of MERS. We obtained the medical records of all
      confirmed cases, interviewed the members of the affected household and reviewed
      the actions taken by the health authorities. All the cases were connected. The
      index case was a 62-year-old man with a history of close contact with dromedary
      camels; three of the seven infected family members and 18 people in hospitals
      died (case-fatality rate, 40.4%). The median incubation period was about 6 days.
      The cluster of cases appeared to be due to high exposure to MERS, delayed
      diagnosis, inadequate risk communication and inadequate compliance of hospital
      health workers and visitors with infection prevention and control measures.

PMID- 27714742
TI  - Capacity of the national influenza surveillance system in Afghanistan, a chronic
      conflict setting.
AB  - Influenza surveillance is needed to monitor potential public health threats from
      the emergence of novel influenza viruses. This study assessed the capacity and
      performance of the national influenza surveillance system in Afghanistan from
      2007 to 2014. Data were collected by review of hospital registers and the
      National Influenza Centre (NIC) database, interviews with influenza focal points
      at 9 influenza sentinel surveillance sites and the Centre staff, and observation
      of the sites. Out of 6900 specimens collected, influenza virus was detected in
      253 (3.6%), predominantly H1N1 (63%); most of these cases were detected during
      the 2009 pandemic. The NIC had the capacity for virus isolation and PCR
      identification and performed reasonably until 2011 when support of the Naval
      American Medical Research Unit 3 was withdrawn. The limitations identified in the
      system indicated the need for: more complete data, improved technical competence
      and trained human resources, updating of the infrastructure/facilities, and the
      presence of standard operating procedures throughout surveillance.

PMID- 27714743
TI  - Circulation of Respiratory Syncytial Virus in Morocco during 2014-2016: Findings
      from a sentinel-based virological surveillance system for influenza.
AB  - Respiratory syncytial virus (RSV) is a leading cause of mortality and morbidity
      in young infants, little was known on its circulation types and patterns in
      Morocco. We conducted a prospective study using sentinel-based influenza
      surveillance to detect RSV by real time PCR in patients with acute respiratory
      infections, enrolled during two seasons (2014/15, 2015/16). During September 2014
      April 2016, we obtained 1450 specimens, of which 267(18.4%) tested positive for
      RSV. The proportion of positive RSV infection was higher in patients hospitalized
      with acute respiratory infection compared to those with mild symptoms in out
      patient clinics. The proportion of RSV infection was highest in children aged 0-6
      months (45%; P < 0.001). Higher positivity rate was observed between months of
      December and March. RSV remains important viral etiological agent causing
      influenza-like illness and severe acute respiratory infections especially among
      infants in Morocco. Further surveillance, is required to understand better the
      risk factors of RSV infections.

PMID- 27714744
TI  - Molecular epidemiology and evolution of A(H1N1) pdm09 and H3N2 viruses in Jordan,
      2011-2013.
AB  - Understanding the genetic evolution of A(H1N1)pdm09 and H3N2 viruses can help
      better select strains to be included in the annual influenza vaccine. There is
      little information on their evolution in Jordan so this study investigated the
      genetic and antigenic variability of A(H1N1)pdm09 and H3N2 viruses in Jordan by
      performing phylogenetic and genetic analyses of the HA and NA genes of
      A(H1N1)pdm09 and H3N2 viruses between 2011 and 2013. The full HA and NA genes of
      16 H1N1-positive samples obtained in our study and 21 published HA sequences and
      20 published NA sequences from Jordanian viruses that were available on online
      gene databases were analysed. For H3N2, we generated 20 HA and 19 NA sequences
      and included 19 published HA and NA sequences each in the analysis. Jordanian
      H1N1 viruses had mutations that are characteristic of antigenic group 6 while
      H3N2 virus mutations belonged to group 3. No markers of resistance to oseltamivir
      were detected. The individual mutations are described in detail.

PMID- 27714745
TI  - Incidence of influenza virus-associated severe acute respiratory infection in
      Damanhour district, Egypt, 2013.
AB  - The epidemiology, seasonality and risk factors for influenza virus infection
      remains poorly defined in countries such as Egypt. Between 1 January and 31
      December 2013, we used surveillance data on patients hospitalized with severe
      acute respiratory infection in three Egyptian government hospitals in Damanhour
      district to estimate the incidence rate of laboratory-confirmed seasonal
      influenza. Samples were taken from 1727 of 1856 patients; of these, 19% were
      influenza virus positive. The overall incidence of influenza virus-associated
      SARI during the study period was estimated to be 44 cases per 100 000 person
      years (95% CI: 39-48). The highest incidence of 166 cases per 100 000 person year
      (95% CI: 125-220) was observed in children aged 2 to 4 years. The incidence of
      influenza-virus associated SARI cases in pregnant women was estimated to be 17.3
      cases per 100 000 person-years (95% CI: 6-54). Majority of influenza virus
      associated SARI occurred in autumn and early winter, and influenza A(H3N2) virus
      predominated. This was the first ever description of the epidemiology of seasonal
      influenza in Egypt. However, additional works are needed for greater
      understanding of influenza burden in Egypt.

PMID- 27714746
TI  - Burden of acute respiratory disease of epidemic and pandemic potential in the WHO
      Eastern Mediterranean Region: A literature review.
AB  - There are gaps in the knowledge about the burden of severe respiratory disease in
      the Eastern Mediterranean Region (EMR). This literature review was therefore
      conducted to describe the burden of epidemicand pandemic-prone acute respiratory
      infections (ARI) in the Region which may help in the development of evidence
      based disease prevention and control policies. Relevant published and unpublished
      reports were identified from searches of various databases; 83 documents
      fulfilled the search criteria. The infections identified included: ARI, avian
      influenza A(H5N1), influenza A(H1N1)pdm09 and Middle East respiratory syndrome
      coronavirus (MERS-CoV) infection. Pneumonia and ARIs were leading causes of
      disease and death in the Region. Influenza A(H1N1) was an important cause of
      morbidity during the 2009 pandemic. This review provides a descriptive summary of
      the burden of acute respiratory diseases in the Region, but there still remains a
      lack of necessary data.

PMID- 27714747
TI  - Influenza virus positivity and circulating subtypes among cases of influenza-like
      illness and severe acute respiratory infection, Egypt, 2012-2015.
AB  - Information on the prevalence of influenza, circulating virus subtypes and
      seasonality is essential for selecting strains for annual vaccines and for
      planning immunization programmes. Data were obtained from the 13 sentinel
      surveillance sites throughout Egypt during 2012-2015. Laboratory-confirmed
      influenza was found in 13% of cases of influenza-like illness (ILI) and 18% of
      cases of severe acute respiratory infection (SARI); positivity for influenza was
      similar in cases of ILI and SARI in patients up to 15 years of age but increased
      for SARI and decreased for ILI in people aged >= 15 years. The most commonly
      observed influenza virus subtypes were B followed by A/ H3 in ILI cases, and
      A/H1N1 followed by B in SARI cases. The seasonality of influenza in ILI cases was
      November- February, and that in SARI cases was November-March, peaking in
      January.

PMID- 27714748
TI  - Middle East respiratory syndrome coronavirus: current knowledge and future
      considerations.
AB  - A literature review of publically available information was undertaken to
      summarize current understanding and gaps in knowledge about Middle East
      respiratory syndrome coronavirus (MERS-CoV), including its origin, transmission,
      effective control measures and management. Major databases were searched and
      relevant published papers and reports during 2012-2015 were reviewed. Of the 2520
      publications initially retrieved, 164 were deemed relevant. The collected results
      suggest that much remains to be discovered about MERS-CoV. Improved surveillance,
      epidemiological research and development of new therapies and vaccines are
      important, and the momentum of recent gains in terms of better understanding of
      disease patterns should be maintained to enable the global community to answer
      the remaining questions about this disease.

PMID- 27714749
TI  - Characterization of influenza outbreaks in Lebanon during the 2013/14 and 2014/15
      seasons.
AB  - Despite the significant burden of influenza outbreaks, active disease monitoring
      has been largely absent in the Middle East, including Lebanon. In this study we
      characterized influenza virus in 440 nasopharyngeal swabs collected from patients
      with acute respiratory infections during two influenza seasons in Lebanon.
      Influenza A(H3N2) was dominant in the 2013/14 season while the A(H1N1)pdm09 and
      B/Yamagata strains were most prevalent in the 2014/15 season. All tested isolates
      were susceptible to 4 neuraminidase inhibitors (oseltamivir, zanamivir, peramivir
      and laninamivir). Genetic analysis of the haemagglutinin gene revealed multiple
      introductions of influenza viruses into Lebanon from different geographic sources
      during each season. Additionally, large data gaps were identified in the Middle
      East region, as indicated by the lack of current influenza sequences in the
      database from many countries in the region.

PMID- 27714750
TI  - The H1N1 influenza pandemic of 2009 in the Eastern Mediterranean Region: lessons
      learnt and future strategy.
AB  - A novel strain of influenza A virus H1N1 surfaced in Mexico in April 2009 and
      quickly spread across the globe, turning an epidemic into a pandemic. Within two
      months, the World Health Organization (WHO) declared an international health
      emergency and raised the threat bar from level V to level VI, i.e. containment to
      mitigation. During this time, the WHO Regional Office for the Eastern
      Mediterranean worked closely with its Member States, other stakeholders and WHO
      headquarters to manage the situation. This report examines the steps taken as
      part of this response. Programme documents were reviewed and key personnel
      interviewed for this study. A hallmark of the response was the establishment of
      the Strategic Health Operations Centre to bring together experts from different
      technical backgrounds at regional level. Several lessons were learnt that can
      provide the basis for standard operating procedures, protocols and guidelines for
      emergency events in future.

PMID- 27714751
TI  - Active surveillance of avian influenza viruses in Egyptian poultry, 2015.
AB  - Surveillance for avian influenza viruses in Egyptian poultry has been conducted
      since 2009. Up to 2011, all the detected viruses were H5N1, and the overall
      prevalence was 5%. In 2011, H9N2 viruses were observed to be co-circulating and
      co-infecting the same hosts as H5N1 viruses. Since then, the detection rate has
      increased to around 10%. In the 2014-2015 winter season, H5N1 was circulating
      heavily in poultry flocks and caused an unprecedented number of human infections.
      In contrast, surveillance in the last quarter of 2015 indicated a near absence of
      H5N1 in Egyptian poultry. Surveillance for avian influenza viruses must continue
      in Egypt to monitor further developments in H5N1 circulation in poultry.

PMID- 27714752
TI  - A new paradigm in global health security.

PMID- 27714753
TI  - Predicted cases of U.K. skin squamous cell carcinoma and basal cell carcinoma in
      2020 and 2025: horizon planning for National Health Service dermatology and
      dermatopathology.

PMID- 27714754
TI  - Paravertebral block and persistent postoperative pain after breast surgery: meta
      analysis and trial sequential analysis.
AB  - We examined whether paravertebral block has an effect on the prevalence of
      persistent postsurgical pain after breast surgery. Seven randomised, controlled
      trials (559 patients) which had the outcome assessor blinded were included,
      comparing patients who received paravertebral blocks after breast surgery with
      patients who did not. The risk ratio (95% CI) was 0.75 (0.48-1.15) for the
      incidence of postoperative pain at 3 months (four studies, 317 patients); the
      risk ratio (95% CI) obtained from three studies including 301 patients reporting
      on pain after 6 months was 0.57 (0.29-1.72), and the risk ratio (95% CI) for pain
      after 12 months (three trials, 237 patients) was 0.42 (0.15-1.23). Conventional
      meta-analysis using the random effects model thus showed no statistically
      significant risk reduction for persistent postoperative pain at 3 months, 6
      months or 12 months. Trial sequential analysis, used to consider the risk of type
      1 and type 2 random error, showed that at 3 months, 6 months and 12 months, the
      number of subjects in the analyses were only 18.3%, 6.8% and 4.2% of the required
      information sizes at those time points, respectively. Our study is the first to
      evaluate data on pain 12 months postoperatively. Trial sequential analysis
      revealed that the current evidence is not sufficient to reach a conclusion. These
      findings stand in contrast to previous meta-analyses with fewer studies that had
      concluded that paravertebral block effectively reduces chronic pain.

PMID- 27714755
TI  - Peri-operative management of anticoagulation and antiplatelet therapy.

PMID- 27714756
TI  - Cardiovascular pharmacogenetics: a promise for genomically-guided therapy and
      personalized medicine.
AB  - Cardiovascular disease (CVD) is the leading cause of death worldwide. The basic
      causes of CVD are not fully understood yet. Substantial evidence suggests that
      genetic predisposition plays a vital role in the physiopathology of this complex
      disease. Hence, identification of genetic contributors to CVD will likely add
      diagnostic accuracy and better prediction of an individual's risk. With high
      throughput genetics and genomics technology and newer genome-wide study
      approaches, a number of genetic variations across the human genome were
      uncovered. Evidence suggests that genetic defects could influence CVD development
      and inter-individual responses to widely used cardiovascular drugs like
      clopidogrel, aspirin, warfarin, and statins, and therefore, they may be
      integrated into clinical practice. If clinically validated, better understanding
      of these genetic variations may provide new opportunities for personalized
      diagnostic, pharmacogenetic-based drug selection and best treatment in
      personalized medicine. However, numerous gaps remain unsolved due to the lack of
      underlying pathological mechanisms for how genetic predisposition could
      contribute to CVD. This review provides an overview of the extraordinary
      scientific progress in our understanding of genetic and genomic basis of CVD as
      well as the development of relevant genetic biomarkers for this disease. Some of
      the actual limitations to the promise of these markers and their translation for
      the benefit of patients will be discussed.

PMID- 27714758
TI  - A randomised, controlled, double blind, non-inferiority trial of ultrasound
      guided fascia iliaca block vs. spinal morphine for analgesia after primary hip
      arthroplasty.
AB  - We performed a single centre, double blind, randomised, controlled, non
      inferiority study comparing ultrasound-guided fascia iliaca block with spinal
      morphine for the primary outcome of 24-h postoperative morphine consumption in
      patients undergoing primary total hip arthroplasty under spinal anaesthesia with
      levobupivacaine. One hundred and eight patients were randomly allocated to
      receive either ultrasound-guided fascia iliaca block with 2 mg.kg-1
      levobupivacaine (fascia iliaca group) or spinal morphine 100 MUg plus a sham
      ultrasound-guided fascia iliaca block using saline (spinal morphine group). The
      pre-defined non-inferiority margin was a median difference between the groups of
      10 mg in cumulative intravenous morphine use in the first 24 h postoperatively.
      Patients in the fascia iliaca group received 25 mg more intravenous morphine than
      patients in the spinal morphine group (95% CI 9.0-30.5 mg, p < 0.001). Ultrasound
      guided fascia iliaca block was significantly worse than spinal morphine in the
      provision of analgesia in the first 24 h after total hip arthroplasty. No
      increase in side-effects was noted in the spinal morphine group but the study was
      not powered to investigate all secondary outcomes.

PMID- 27714757
TI  - The protective effect of the natural compound hesperetin against fulminant
      hepatitis in vivo and in vitro.
AB  - BACKGROUND AND PURPOSE: Liver diseases are mostly accompanied by inflammation and
      hepatocyte death. Therapeutic approaches targeting both hepatocyte injury and
      inflammation are not available. Natural compounds are considered as potential
      treatment for inflammatory liver diseases. Hesperetin, a flavonoid component of
      citrus fruits, has been reported to have anti-inflammatory properties. The aim of
      this study was to evaluate the cytoprotective and anti-inflammatory properties of
      hesperetin both in vitro and in models of fulminant hepatitis. EXPERIMENTAL
      APPROACH: Apoptotic cell death and inflammation were induced in primary cultures
      of rat hepatocytes by bile acids and cytokine mixture respectively. Apoptosis was
      quantified by caspase-3 activity and necrosis by LDH release. The concanavalin A
      (ConA) and D-galactosamine/LPS (D-GalN/LPS) were used as models of fulminant
      hepatitis. Liver injury was assessed by alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) levels, liver histology and TUNEL assay and
      inflammation by inducible NOS (iNOS) expression. KEY RESULTS: Hesperetin blocked
      bile acid-induced apoptosis and cytokine-induced inflammation in rat hepatocytes.
      Moreover, hesperetin improved liver histology and protected against hepatocyte
      injury in ConA- and D-GalN/LPS-induced fulminant hepatitis, as assessed by TUNEL
      assay and serum AST and ALT levels. Hesperetin also reduced expression of the
      inflammatory marker iNOS and the expression and serum levels of TNFalpha and IFN
      gamma, the main mediators of cell toxicity in fulminant hepatitis. CONCLUSION AND
      IMPLICATIONS: Hesperetin has anti-inflammatory and cytoprotective actions in
      models of acute liver toxicity. Hesperetin therefore has therapeutic potential
      for the treatment of inflammatory liver diseases accompanied by extensive
      hepatocyte injury, such as fulminant hepatitis.

PMID- 27714759
TI  - Prevalence of human papillomavirus infection among women in rural Nepal.
AB  - INTRODUCTION: In this study we aimed to determine the overall and type-specific
      prevalence of cervical human papillomavirus (HPV) infection and risk factors for
      such infection among women in rural Nepal, and to investigate the distribution of
      HPV infection by cervical cytology. MATERIAL AND METHODS: The study was conducted
      among women aged >=15 years in five rural villages within Kavre District in
      Nepal. Sociodemographic data and information on risk factors for cervical cancer
      were obtained through an interview, and a cervical specimen was collected for HPV
      DNA detection and typing using the AnyplexTM ll HPV28 Detection system, and for
      Papanicolaou test. RESULTS: Among the 1289 women in whom a valid HPV result was
      obtained the median age was 40 years (range 17-86 years). Overall, the HPV
      prevalence was 14.4%, 7.9% for high-risk and 6.5% for low-risk HPV types, and was
      similar between age groups. The five most common HR types were HPV-18 (2.3%), HPV
      51 (1.2%), HPV-59 (1.1%), HPV-31 (0.9%), and HPV-16 (0.8%). The prevalence of
      high-risk types in women with and without abnormal cytology was 8.3 and 7.7%,
      respectively. HPV infection was associated with current smoking, formal
      education, and being married to a husband with at least one previous marriage.
      CONCLUSIONS: This is the first population-based study to report the prevalence of
      a broad range of HPV types among women from rural Nepal. These data are crucial
      for development of preventive strategies to reduce cervical cancer burden in the
      country.

PMID- 27714761
TI  - A phase II trial of TBL-12 sea cucumber extract in patients with untreated
      asymptomatic myeloma.

PMID- 27714760
TI  - Role of oxidative stress in oxaliplatin-induced enteric neuropathy and colonic
      dysmotility in mice.
AB  - BACKGROUND AND PURPOSE: Oxaliplatin is a platinum-based chemotherapeutic drug
      used as a first-line therapy for colorectal cancer. However, its use is
      associated with severe gastrointestinal side-effects resulting in dose
      limitations and/or cessation of treatment. In this study, we tested whether
      oxidative stress, caused by chronic oxaliplatin treatment, induces enteric
      neuronal damage and colonic dysmotility. EXPERIMENTAL APPROACH: Oxaliplatin (3
      mg.kg-1 per day) was administered in vivo to Balb/c mice intraperitoneally three
      times a week. The distal colon was collected at day 14 of treatment.
      Immunohistochemistry was performed in wholemount preparations of submucosal and
      myenteric ganglia. Neuromuscular transmission was studied by intracellular
      electrophysiology. Circular muscle tone was studied by force transducers. Colon
      propulsive activity studied in organ bath experiments and faeces were collected
      to measure water content. KEY RESULTS: Chronic in vivo oxaliplatin treatment
      resulted in increased formation of reactive oxygen species (O2 -), nitration of
      proteins, mitochondrial membrane depolarisation resulting in the release of
      cytochrome c, loss of neurons, increased inducible NOS expression and apoptosis
      in both the submucosal and myenteric plexuses of the colon. Oxaliplatin treatment
      enhanced NO-mediated inhibitory junction potentials and altered the response of
      circular muscles to the NO donor, sodium nitroprusside. It also reduced the
      frequency of colonic migrating motor complexes and decreased circular muscle
      tone, effects reversed by the NO synthase inhibitor, Nomega-Nitro-L-arginine.
      CONCLUSION AND IMPLICATIONS: Our study is the first to provide evidence that
      oxidative stress is a key player in enteric neuropathy and colonic dysmotility
      leading to symptoms of chronic constipation observed in oxaliplatin-treated mice.

PMID- 27714762
TI  - Reductions in Medication-Related Hospitalizations in Older Adults with Medication
      Management by Hospital and Community Pharmacists: A Quasi-Experimental Study.
AB  - OBJECTIVES: To evaluate the association between a system of medication management
      services provided by specially trained hospital and community pharmacists
      (Pharm2Pharm) and rates and costs of medication-related hospitalization in older
      adults. DESIGN: Quasi-experimental interrupted time series design comparing
      intervention and nonintervention hospitals using a mixed-effects analysis that
      modeled the intervention as a time-dependent variable. SETTING: Sequential
      implementation of Pharm2Pharm at six general nonfederal acute care hospitals in
      Hawaii with more than 50 beds in 2013 and 2014. All five other such hospitals
      served as a contemporaneous comparison group. PARTICIPANTS: Adult inpatients who
      met criteria for being at risk for medication problems (N = 2,083), 62% of whom
      were aged 65 or older. INTERVENTION: A state-wide system of medication management
      services provided by specially trained hospital and community pharmacists serving
      high-risk individuals from hospitalization through transition to home and for up
      to 1 year after discharge. MEASUREMENTS: Medication-related hospitalization rate
      per 1,000 admissions of individuals aged 65 and older, adjusted for case mix;
      estimate of costs of hospitalizations and actual costs of pharmacist services.
      RESULTS: The predicted, case mix-adjusted medication-related hospitalization rate
      of individuals aged 65 and older was 36.5% lower in the Pharm2Pharm hospitals
      after implementation than in the nonintervention hospitals (P = .01). The
      estimated annualized cost of avoided admissions was $6.6 million. The annual cost
      of the pharmacist services for all Pharm2Pharm participants was $1.8 million.
      CONCLUSION: The Pharm2Pharm model was associated with an estimated 36% reduction
      in the medication-related hospitalization rate for older adults and a 2.6:1
      return on investment, highlighting the value of pharmacists as drug therapy
      experts in geriatric care.

PMID- 27714763
TI  - Amiselimod, a novel sphingosine 1-phosphate receptor-1 modulator, has potent
      therapeutic efficacy for autoimmune diseases, with low bradycardia risk.
AB  - BACKGROUND AND PURPOSE: We conducted preclinical and clinical studies to examine
      the pharmacological, particularly cardiac, effects of amiselimod (MT-1303), a
      second-generation sphingosine 1-phosphate (S1P) receptor modulator, designed to
      reduce the bradycardia associated with fingolimod and other S1P receptor
      modulators. EXPERIMENTAL APPROACH: The selectivity of the active metabolite
      amiselimod phosphate (amiselimod-P) for human S1P receptors and activation of G
      protein-coupled inwardly rectifying K+ (GIRK) channels in human atrial myocytes
      were assessed. Its cardiac distribution was determined in rats, and
      cardiovascular telemetry was assessed in monkeys. We also examined the
      pharmacokinetics, pharmacodynamics and safety of amiselimod in healthy humans.
      KEY RESULTS: Amiselimod-P showed potent selectivity for S1P1 and high selectivity
      for S1P5 receptors, with minimal agonist activity for S1P4 and no distinct
      agonist activity for S1P2 or S1P3 receptors and approximately five-fold weaker
      GIRK activation than fingolimod-P. After oral administration of amiselimod or
      fingolimod at 1 mg.kg-1 , the concentration of amiselimod-P in rat heart tissue
      was lower than that of fingolimod-P, potentially contributing to the minimal
      cardiac effects of amiselimod. A telemetry study in monkeys confirmed that
      amiselimod did not affect heart rate or ECG parameters. In healthy human
      subjects, peripheral blood lymphocyte counts gradually reduced over the 21 day
      dosing period, with similar lymphocyte count profiles with the highest doses by
      day 21, and no clinically significant bradycardia observed on day 1 or during the
      study. CONCLUSIONS AND IMPLICATIONS: Amiselimod exhibited potent therapeutic
      efficacy with minimal cardiac effects at the anticipated clinical dose and is
      unlikely to require dose titration.

PMID- 27714764
TI  - Utilization of next generation sequencing identifies potentially actionable
      mutations in chronic lymphocytic leukaemia.

PMID- 27714765
TI  - Short-term efficacy and safety of antithymocyte globulin treatment in elderly
      patients with acquired aplastic anaemia.

PMID- 27714766
TI  - An observational study of critical care physicians' assessment and decision
      making practices in response to patient referrals.
AB  - Previous studies of critical care admissions have largely compared patients that
      have been granted or declined admission. To better understand the decision
      process itself, our ethnographic approach combined observation of and interviews
      with critical care physicians in a large English hospital. We observed 30
      critical care doctors managing 71 referrals and conducted ten interviews with
      senior decision-makers to explore the themes raised by our observations. We
      analysed data using the constant comparative method. We found that the decision
      to move a patient to critical care was just one way in which the trajectory of
      critical illness could be modified. When patients were admitted to critical care,
      it was not always for invasive monitoring or advanced organ support, with some
      admitted for more general medical and/or nursing care. When patients were
      declined admission, they were not simply forgotten or left behind; they
      nevertheless underwent careful assessment and follow-up. Thus, depicting
      admission or refusal as a binary event is misleading. We suggest that
      prescriptive admission algorithms are problematic for clinicians, in that they
      may not take into account the complexity of clinical practice.

PMID- 27714767
TI  - "Mock before you block": an in-built action-check to prevent wrong-side
      anaesthetic nerve blocks.

PMID- 27714768
TI  - Effects of S906T polymorphism on the severity of a novel borderline mutation
      I692M in Nav 1.4 cause periodic paralysis.
AB  - Hyperkalemic periodic paralysis (HyperPP) is a dominantly inherited muscle
      disease caused by mutations in SCN4A gene encoding skeletal muscle voltage gated
      Nav 1.4 channels. We identified a novel Nav 1.4 mutation I692M in 14 families out
      of the 104 genetically identified HyperPP families in the Neuromuscular Centre
      Ulm and is therefore as frequent as I693T (13 families out of 14 HyperPP
      families) in Germany. Surprisingly, in 13 families, a known polymorphism S906T
      was also present. It was on the affected allele in at least 10 families
      compatible with a possible founder effect in central Europe. All affected members
      suffered from episodic weakness; myotonia was also common. Compared with I692M
      patients, I692M-S906T patients had longer weakness episodes, more affected
      muscles, CK elevation and presence of permanent weakness. Electrophysiological
      investigation showed that both mutants had incomplete slow inactivation and a
      hyperpolarizing shift of activation which contribute to membrane depolarization
      and weakness. Additionally, I692M-S906T significantly enhanced close-state fast
      inactivation compared with I692M alone, suggesting a higher proportion of
      inactivated I692M-S906T channels upon membrane depolarization which may
      facilitate the initiation of weakness episodes and therefore clinical
      manifestation. Our results suggest that polymorphism S906T has effects on the
      clinical phenotypic and electrophysiological severity of a novel borderline Nav
      1.4 mutation I692M, making the borderline mutation fully penetrant.

PMID- 27714769
TI  - Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against
      levetiracetam background therapy.
AB  - OBJECTIVE: To assess prospectively the effectiveness of lacosamide (LCM) added to
      levetiracetam (LEV) after down-titration of a concomitant sodium channel blocker
      (SCB) among patients with focal epilepsy not adequately controlled on LEV and
      SCB. METHODS: In this open-label trial, LCM was initiated at 100 mg/day and up
      titrated to 200-600 mg/day over 9 weeks; SCB down-titration started when LCM dose
      reached 200 mg/day. Patients remained on stable LCM/LEV doses for 12 weeks'
      maintenance (21-week treatment period). The primary outcome was retention rate on
      LCM. RESULTS: Due to recruitment challenges, fewer than the planned 300 patients
      participated in the trial, resulting in the trial being underpowered. Overall,
      120 patients (mean age 39.7 years) started and 93 completed the trial. The most
      frequently used SCBs were lamotrigine (39.2%), carbamazepine (30.8%) and
      oxcarbazepine (27.5%). Eighty-four patients adhered to protocol and discontinued
      their SCB after cross-titration, but there was insufficient evidence for 36
      patients. Retention rate was 73.3% (88/120) for all patients and 83.3% (70/84)
      for those with evidence of SCB discontinuation. Seizure freedom for patients
      completing maintenance was 14.0% (13/93). Discontinuation due to adverse events
      (6.7%) and lack of efficacy (3.3%) occurred primarily during cross-titration.
      Most frequently reported adverse events during treatment were dizziness (23.3%),
      headache (15.0%) and fatigue (8.3%). CONCLUSIONS: In patients with uncontrolled
      seizures on LEV/SCB, the LCM/LEV combination appeared to be effective and well
      tolerated. A cross-titration schedule-flexible LCM up-titration, concomitant SCB
      down-titration and stable background LEV-could present a feasible and practical
      approach to initiating LCM while minimizing pharmacodynamic interactions with a
      SCB.

PMID- 27714770
TI  - Subthreshold and threshold attention deficit hyperactivity disorder symptoms in
      childhood: psychosocial outcomes in adolescence in boys and girls.
AB  - OBJECTIVE: To examine the association between different levels of childhood
      attention deficit hyperactivity disorder (ADHD) symptoms and sex differences in
      psychosocial outcomes during adolescence. METHOD: Swedish children (n = 4635)
      were screened for neuropsychiatric symptoms at age 9 or 12. ADHD symptoms were
      divided into three levels: screen-negative, screen-intermediate, and screen
      positive. At follow-up (age 15), parents and teenagers filled out questionnaires
      regarding (i) hyperactivity/inattention, (ii) peer problems, (iii) school
      problems, (iv) internalizing problems, (v) antisocial behaviour, (vi) alcohol
      misuse, and (vii) drug misuse. All outcomes were controlled for symptoms of
      diagnostic categories other than ADHD. RESULTS: Increasing levels of ADHD
      symptoms in childhood were associated with higher proportions of adolescents who
      displayed negative psychosocial outcomes. More girls than boys reported
      internalizing problems (all levels) and risky drug use (screen-intermediate and
      screen-positive only). More boys reported antisocial behaviour at the screen
      negative and screen-intermediate levels, but at the screen-positive level,
      similar proportions of girls and boys displayed antisocial behaviour. CONCLUSION:
      The findings support the view that ADHD symptoms, as well as their negative
      outcomes, are dimensionally distributed in the population and that adolescent
      girls and boys display different risk profiles. The findings confirm that ADHD
      symptoms are associated with higher risk of drug misuse in girls.

PMID- 27714771
TI  - In Vitro Functional Analyses of Infrequent Nucleotide Variants in the Lactase
      Enhancer Reveal Different Molecular Routes to Increased Lactase Promoter Activity
      and Lactase Persistence.
AB  - The genetic trait that allows intestinal lactase to persist into adulthood in
      some 35% of humans worldwide operates at the level of transcription, the effect
      being caused by cis-acting nucleotide changes upstream of the lactase gene (LCT).
      A single nucleotide substitution, -13910 C>T, the first causal variant to be
      identified, accounts for lactase persistence over most of Europe. Located in a
      region shown to have enhancer function in vitro, it causes increased activity of
      the LCT promoter in Caco-2 cells, and altered transcription factor binding. Three
      other variants in close proximity, -13907 C>G, -13915 T>C and -14010 G>C, were
      later shown to behave in a similar manner. Here, we study four further candidate
      functional variants. Two, -14009 T>G and -14011 C>T, adjacent to the well-studied
      -14010 G>C variant, also have a clear effect on promoter activity upregulation as
      assessed by transfection assays, but notably are involved in different molecular
      interactions. The results for the two other variants (-14028 T>C, -13779 G>C)
      were suggestive of function, -14028*C showing a clear change in transcription
      factor binding, but no obvious effect in transfections, while -13779*G showed
      greater effect in transfections but less on transcription factor binding. Each of
      the four variants arose on independent haplotypic backgrounds with different
      geographic distribution.

PMID- 27714772
TI  - Mammalian-target of rapamycin inhibition with temsirolimus in myelodysplastic
      syndromes (MDS) patients is associated with considerable toxicity: results of the
      temsirolimus pilot trial by the German MDS Study Group (D-MDS).
AB  - The mammalian-target of rapamycin (also termed mechanistic target of rapamycin,
      mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and
      is involved in regulatory T-cell (TREG) development. As these processes
      contribute to the pathogenesis of myelodysplastic syndromes (MDS), we
      hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in
      MDS. This prospective multicentre trial enrolled lower and higher risk MDS
      patients, provided that they were transfusion-dependent/neutropenic or
      relapsed/refractory to 5-azacitidine, respectively. All patients received TEM at
      a weekly dose of 25 mg. Of the 9 lower- and 11 higher-risk patients included,
      only 4 (20%) reached the response assessment after 4 months of treatment and
      showed stable disease without haematological improvement. The remaining patients
      discontinued TEM prematurely due to adverse events. Median overall survival (OS)
      was not reached in the lower-risk group and 296 days in the higher-risk group. We
      observed a significant decline of bone marrow (BM) vascularisation (P = 0.006)
      but were unable to demonstrate a significant impact of TEM on the balance between
      TREG and pro-inflammatory T-helper-cell subsets within the peripheral blood or
      BM. We conclude that mTOR-modulation with TEM at a dose of 25 mg per week is
      accompanied by considerable toxicity and has no beneficial effects in elderly MDS
      patients.

PMID- 27714774
TI  - Similar incidence of severe acute GVHD and less severe chronic GVHD in PBSCT from
      unmanipulated, haploidentical donors compared with that from matched sibling
      donors for patients with haematological malignancies.
AB  - The features of graft-versus-host disease (GVHD) were compared between patients
      who underwent myeloablative conditioning and received a peripheral blood stem
      cell transplant (PBSCT) from either a haploidentical donor (HID) or a matched
      sibling donor (MSD) during the same period of time. The HID group included more
      patients with advanced disease. Both groups received the same GVHD prophylaxis
      with the addition of antithymoglobulin (ATG) in HID group. Higher cumulative
      incidences (CI) of acute GVHD grade 2-4 (35.1% vs. 13.9%, P = 0.003), similar CI
      of grade 3-4 (14.5% vs. 9.8%, P = 0.595), less 3-year CI of extensive chronic
      GVHD (17.1% vs. 41.5%, P = 0.017) and less severe chronic GVHD (5.8% vs. 21.2%, P
      = 0.049) occurred in the HID group compared with the MSD group. There was no
      difference in the sites of the involved organs between these two groups. Higher 3
      year CI of non-relapse mortality (24.0% vs. 10.2%, P = 0.014), relapse (39.0% vs.
      22.6%, P = 0.032) and inferior disease-free survival (45.7% vs. 78.9%, P = 0.000)
      were recorded in the HID cohort compared with the MSD group. More HID patients
      had Karnofsky scores above 90 than those in MSD group (P = 0.016). In conclusion,
      ATG plays a key role in the unmanipulated HID PBSCT protocol, producing better
      quality of life in survivors.

PMID- 27714773
TI  - Histamine H4 receptor agonist-induced relief from painful peripheral neuropathy
      is mediated by inhibition of spinal neuroinflammation and oxidative stress.
AB  - BACKGROUND AND PURPOSE: Neuropathic pain is under-treated, with a detrimental
      effect on quality of life, partly because of low treatment efficacy, but also
      because pathophysiological mechanisms are not fully elucidated. To clarify the
      pathobiology of neuropathic pain, we studied the contribution of
      neuroinflammation and oxidative stress in a model of peripheral neuropathy. We
      also assessed an innovative treatment for neuropathic pain by investigating the
      effects of histamine H4 receptor ligands in this model. EXPERIMENTAL APPROACH: A
      peripheral mononeuropathy was induced in mice, by spared nerve injury (SNI).
      Neuroinflammation and oxidative stress parameters were evaluated by
      spectrophotometry. The mechanical (von Frey test) and thermal (plantar test)
      nociceptive thresholds were evaluated. KEY RESULTS: SNI mice showed increased
      expression of the pro-inflammatory cytokines IL-1beta and TNF-alpha, decreased
      antioxidant enzyme Mn-containing SOD (MnSOD), increased levels of 8-hydroxy-2'
      deoxyguanosine (8-OHdG), an indicator of oxidative DNA damage, and of PARP,
      nuclear enzyme activated upon DNA damage. Intrathecal administration of VUF 8430
      (H4 receptor agonist) reversed the mechanical and thermal allodynia and was
      associated with decreased expression of IL-1beta, TNF-alpha, 8-OHdG and PARP and
      with restoration of MnSOD activity in the spinal cord and sciatic nerve. These
      effects were prevented by JNJ 10191584 (H4 receptor antagonist). CONCLUSION AND
      IMPLICATIONS: In the SNI mouse model of neuropathic pain, neuronal H4 receptor
      stimulation counteracts hyperalgesia and reduces neuroinflammation and oxidative
      stress in the spinal cord and sciatic nerve. Targeting both oxidative stress and
      pro-neuroinflammatory pathways through H4 receptor-mediated mechanisms could have
      promising therapeutic potential for neuropathic pain management.

PMID- 27714775
TI  - Detection of fetal abnormalities by second-trimester ultrasound screening in a
      non-selected population.
AB  - INTRODUCTION: This study assessed the sensitivity of routine ultrasound
      examination for the detection of abnormal chromosomes and structural
      malformations in fetuses in the second trimester in a non-selected population.
      MATERIAL AND METHODS: Prenatal diagnoses of fetal abnormalities in 10 414 fetuses
      and newborns were reviewed and compared with all postnatal diagnoses of
      congenital abnormalities between 2006 and 2013. RESULTS: Overall, 243 fetuses and
      newborns had confirmed congenital abnormalities, with a prevalence of 2.3%. Of
      these fetuses and newborns, 23% (56/243) had chromosomal abnormalities (overall
      prevalence 0.5%), and 77% (187/243) had normal chromosomes with either major
      (44%; 82/187) or minor (56%; 105/187) structural malformations (overall
      prevalence 1.8%). One hundred and seven abnormalities were detected prenatally,
      yielding a total sensitivity for prenatal detection of fetal abnormalities of
      44.0% (107/243; 95% CI 37.8-50.2), with specificity of 99.9%, a positive
      predictive value of 94.7%, and a negative predictive value of 98.7%. The
      sensitivity for prenatal detection before 22 weeks of gestation was 40.3%
      (98/243; 95% CI 34.1-46.5). The prenatal detection rate of chromosomal
      abnormalities was 60.7% (34/56) and, for structural malformations, was 39.0%
      (73/187). CONCLUSIONS: In a routine clinical setting at a county hospital with a
      non-selected population, half of the major structural malformations in
      chromosomally normal fetuses are detected by routine ultrasound examination in
      the second trimester. Chromosomal abnormalities have the highest probability for
      prenatal detection; the majority are diagnosed by amniocentesis before the
      routine ultrasound examination in high-risk women.

PMID- 27714777
TI  - Multiprofessional evaluation in clinical practice: establishing a core set of
      outcome measures for children with cerebral palsy.
AB  - AIM: To develop a national consensus on outcome measures that define functional
      ability in children with cerebral palsy (CP) according to the International
      Classification of Functioning, Disability and Health (ICF) framework. METHOD: The
      project started in 2008 in neuropaediatric units of two university hospitals and
      one outpatient clinic. Each professional group selected representatives to be
      knowledge brokers for their own specialty. Based on the evidence, expert opinion,
      and the ICF framework, multiprofessional teams selected the most valid measures
      used in clinical practice (2009-2010). Data from 269 children with CP were
      analysed, classified by the Gross Motor Function Classification System, Manual
      Ability Classification System, and Communication Function Classification System,
      and evaluated. RESULTS: The process aimed at improving and unifying clinical
      practice in Finland through a national consensus on the core set of measures. The
      selected measures were presented by professional groups, and consensus was
      reached on the recommended core set of measures to be used in all hospitals
      treating children with CP in Finland. INTERPRETATION: A national consensus on
      relevant and feasible measures is essential for identifying differences in the
      effectiveness of local practices, and for conducting multisite intervention
      studies. This project showed that multiprofessional rehabilitation practices can
      be improved through respect for and inclusion of everyone involved.

PMID- 27714776
TI  - Trastuzumab cardiotoxicity: from clinical trials to experimental studies.
AB  - : Epidermal growth factor receptor-2 (HER-2) is overexpressed in 20 to 25% of
      human breast cancers, which is associated with aggressive tumour growth and poor
      prognosis. Trastuzumab (Herceptin(r)) is a humanized monoclonal antibody directed
      against HER-2, the first highly selective form of therapy targeting HER-2
      overexpressing tumours. Although initial trials indicated high efficacy and a
      favourable safety profile of the drug, the first large, randomized trial prompted
      a retrospective analysis of cardiac dysfunction in earlier trials utilizing
      trastuzumab. There has been ongoing debate on the cardiac safety of trastuzumab
      ever since, initiating numerous clinical and preclinical investigations to better
      understand the background of trastuzumab cardiotoxicity and evaluate its effects
      on patient morbidity. Here, we have given a comprehensive overview of our current
      knowledge on the cardiotoxicity of trastuzumab, primarily focusing on data from
      clinical trials and highlighting the main molecular mechanisms proposed. LINKED
      ARTICLES: This article is part of a themed section on New Insights into
      Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in
      this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc.

PMID- 27714778
TI  - Meta-analysis of the use of surgical sealants for suture-hole bleeding in
      arterial anastomoses.
AB  - BACKGROUND: Suture-hole bleeding in arterial anastomoses prolongs operating time
      and increases blood loss, particularly with the use of prosthetic grafts.
      Surgical sealants (such as fibrin) may be used as haemostatic adjuncts in
      vascular surgery. This is a systematic review and meta-analysis of published
      studies that investigated the utility of surgical sealants in arterial-to
      prosthetic graft anastomoses. METHODS: A systematic review was undertaken of
      papers published until January 2015 on Embase, MEDLINE, PubMed, PubMed Central
      and Cochrane databases that analysed the use of surgical sealants as haemostatic
      adjuncts after arterial anastomoses. RCTs were included, with study endpoints of
      time to haemostasis or haemostasis at 5 min. Secondary outcomes included
      treatment failure, mean difference in estimated blood loss and duration of
      surgery. Sensitivity and subgroup analyses were performed, as well as funnel plot
      analysis for publication bias. RESULTS: A total of 2513 citations were reviewed;
      19 RCTs comprising 1560 patients were ultimately included in the analysis. The
      majority of studies compared fibrin sealant with control haemostatic measures.
      Pooled analysis suggested that surgical sealants reduced the time to haemostasis
      (mean difference 243.26 (95 per cent c.i. 183.99 to 302.53) s; P < 0.001),
      improved haemostasis at 5 min (odds ratio 4.50, 95 per cent c.i. 2.59 to 7.81; P
      < 0.001), and were associated with less treatment failure, blood loss and shorter
      duration of surgery. CONCLUSION: Surgical sealants appear to reduce suture-hole
      bleeding significantly in vascular prosthetic graft anastomoses compared with
      standard haemostatic measures.

PMID- 27714779
TI  - Pharmacological mechanisms underlying the cardiovascular effects of the "bath
      salt" constituent 3,4-methylenedioxypyrovalerone (MDPV).
AB  - BACKGROUND AND PURPOSE: 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic
      cathinone with stimulatory cardiovascular effects that can lead to serious
      medical complications. Here, we examined the pharmacological mechanisms
      underlying these cardiovascular actions of MDPV in conscious rats. EXPERIMENTAL
      APPROACH: Male Sprague-Dawley rats had telemetry transmitters surgically
      implanted for the measurement of BP and heart rate (HR). On test days, rats were
      placed individually in standard isolation cubicles. Following drug treatment,
      cardiovascular parameters were monitored for 3 h sessions. KEY RESULTS: Racemic
      MDPV (0.3-3.0 mg.kg-1 ) increased BP and HR in a dose-dependent manner. The S(+)
      enantiomer (0.3-3.0 mg.kg-1 ) of MDPV produced similar effects, while the R(-)
      enantiomer (0.3-3.0 mg.kg-1 ) had no effects. Neither of the hydroxylated phase I
      metabolites of MDPV altered cardiovascular parameters significantly from
      baseline. Pretreatment with the ganglionic blocker chlorisondamine (1 and 3 mg.kg
      1 ) antagonized the increases in BP and HR produced by 1 mg.kg-1 MDPV. The alpha1
      -adrenoceptor antagonist prazosin (0.3 mg.kg-1 ) attenuated the increase in BP
      following MDPV, while the beta-adrenoceptor antagonists propranolol (1 mg.kg-1 )
      and atenolol (1 and 3 mg.kg-1 ) attenuated the HR increases. CONCLUSIONS AND
      IMPLICATIONS: The S(+) enantiomer appeared to mediate the cardiovascular effects
      of MDPV, while the metabolites of MDPV did not alter BP or HR significantly; MDPV
      increased BP and HR through activation of central sympathetic outflow. Mixed
      action alpha/beta-adrenoceptor antagonists may be useful as treatments in
      counteracting the adverse cardiovascular effects of MDPV.

PMID- 27714780
TI  - Linagliptin-associated bullous pemphigoid that was most likely caused by IgG
      autoantibodies against the midportion of BP180.

PMID- 27714782
TI  - N-terminal polar amino acids of the C2 insert of nonmuscle myosin II-C2 regulate
      its functional properties.
AB  - In this study, we investigated the regions in the alternatively spliced C2 insert
      of nonmuscle myosin (NM) II-C conferring unique functional properties to the
      protein. We used constructs carrying deletions within different regions of C2 in
      neuronal cells; namely, the polar N terminus, the proline/serine-rich middle, and
      the nonpolar C terminus. We compared the wild-type NM II-C2 and deletion mutants
      with respect to ATPase activity, coassembly with NM II-B, regulation by myosin
      light-chain kinase (MLCK), and solubility, to determine the C2 region(s) involved
      in these processes. In addition, we examined the ability of the mutants to rescue
      the neurite-shortening phenotype upon NM II-C2 knockdown in Neuro-2a cells. Our
      data highlight the importance of the polar N terminus in NM II-C2 function.

PMID- 27714781
TI  - Effect of topical imiquimod as primary treatment for lentigo maligna: the LIMIT-1
      study.
AB  - BACKGROUND: Topical imiquimod is sometimes used for lentigo maligna (LM) in situ
      melanoma instead of surgery, but frequency of cure is uncertain. Pathological
      complete regression (pCR) is a logical surrogate marker for cure after imiquimod,
      although residual LM and atypical melanocytic hyperplasia may not be reliably
      distinguished. A trial comparing imiquimod vs. surgery might be justified by a
      high imiquimod pCR rate. OBJECTIVES: Primary: to estimate the pCR rate for LM
      following imiquimod. Secondary: to assess the accuracy of prediction of pCR,
      using clinical complete regression (cCR) plus negative post-treatment biopsies,
      tolerability, resource use, patients' preferences and induced melanoma immunity.
      METHODS: This was a single-arm phase II trial of 60 imiquimod applications over
      12 weeks for LM then radical resection. A pCR rate >= 25 out of 33 would reliably
      discriminate between pCR rates < 60% and >= 85%. Clinical response was assessed
      and biopsies taken after imiquimod. Patients recorded adverse events in diaries.
      Patient preference was measured after surgery using a standard gamble tool.
      RESULTS: The pCR rate was 10 of 27 (37%, 95% confidence interval 19-58%). The
      rate of cCR plus negative biopsies was 12 of 28, of whom seven of 11 had pCR on
      subsequent surgery. The median dose intensity was 86.7%. Of the 16 surveyed
      patients, eight preferred primary imiquimod over surgery if the cure rate for
      imiquimod was 80%, and four of 16 if it was <= 40%. CONCLUSIONS: The pCR rate was
      insufficient to justify phase III investigation of imiquimod vs. SURGERY:
      Clinical complete response and negative targeted biopsies left uncertainty
      regarding pathological clearance. Some patients would trade less aggressive
      treatment of LM against efficacy.

PMID- 27714783
TI  - Mate guarding and frequent copulation in birds: A meta-analysis of their
      relationship to paternity and male phenotype.
AB  - In many birds, males are presumed to protect their paternity by closely guarding
      their mate or copulating frequently with her. Both these costly behaviors are
      assumed to reduce the risk and/or intensity of sperm competition. However,
      despite many studies on avian extra-pair paternity, it remains unclear how
      strongly these behaviors are related to fitness and other key life-history
      traits. Here, we conduct meta-analyses to address two questions. First, are mate
      guarding and/or frequent copulation positively correlated with a male's share of
      paternity at his nest? We find a significant positive correlation between both
      presumed paternity protection behaviors and paternity share. The relationship is,
      however, weak (r = 0.08-0.23). This is perhaps unsurprising if the risk of
      partner infidelity, hence the need to protect paternity, varies among males. For
      example, more attractive males might have less need to protect their paternity.
      Second, do males with higher indices of so-called male "quality" (phenotypic
      measures, usually subjectively defined by researchers as predictors of male
      attractiveness) exhibit lower levels of paternity protection behavior? We find a
      negative correlation between male quality and paternity protection. This finding
      might partly explain the weak relationship between paternity protection and
      paternity, although we discuss other, nonmutually exclusive possibilities.

PMID- 27714785
TI  - Behavioral development in embryonic and early juvenile cuttlefish (Sepia
      officinalis).
AB  - Though a mollusc, the cuttlefish Sepia officinalis possesses a sophisticated
      brain, advanced sensory systems, and a large behavioral repertoire. Cuttlefish
      provide a unique perspective on animal behavior due to their phylogenic distance
      from more traditional (vertebrate) models. S. officinalis is well-suited to
      addressing questions of behavioral ontogeny. As embryos, they can perceive and
      learn from their environment and experience no direct parental care. A marked
      progression in learning and behavior is observed during late embryonic and early
      juvenile development. This improvement is concomitant with expansion and
      maturation of the vertical lobe, the cephalopod analog of the mammalian
      hippocampus. This review synthesizes existing knowledge regarding embryonic and
      juvenile development in this species in an effort to better understand cuttlefish
      behavior and animal behavior in general. It will serve as a guide to future
      researchers and encourage greater awareness of the utility of this species to
      behavioral science.

PMID- 27714784
TI  - Platelets Toll-like receptor-4 in Crohns disease.
AB  - BACKGROUND: Platelets are activated in Crohn's disease (CD) and interplay with
      leukocytes. Engagement of Toll-like receptor-4 (TLR-4), which is expressed in
      human platelets, may be involved in crosstalks between platelets and leukocytes
      leading to their mutual activation for host defense. MATERIALS AND METHODS: Human
      neutrophil peptides (HNPs), lipoprotein binding peptides, and sCD14 were
      determined by enzyme-linked immunosorbent assays in 42 patients with active CD,
      in 43 patients with CD in remission, and in 30 healthy individuals. Neutrophil
      platelet aggregates and binding of the TLR-4 monoclonal antibody to platelets
      were determined by flow cytometry. RESULTS: Levels of HNPs were higher in
      patients with CD than in controls (P = 0.0003 vs. active CD and P = 0.01 vs. CD
      in remission). Likewise, neutrophils with adhering platelets were higher in
      patients with active CD than in controls (P = 0.004). Binding of the TLR-4
      antibody in patients with active CD was similar to that in controls, while
      patients in remission had significantly higher binding capacities (P = 0.59 and P
      = 0.003). Incubation of plasma from patients with active disease or patients in
      remission with platelets from healthy controls confirmed lower binding of the TLR
      4 antibody in the presence of plasma from active diseased patients compared to
      controls (P = 0.039), possibly due to high levels of lipopolysaccharides, as
      suggested by high levels of sCD14 and lipoprotein binding protein. CONCLUSION:
      Our study indicates involvement of platelet TLR-4 in enhancing the secretion of
      antimicrobial peptides from neutrophils. While platelet aggregation can be due to
      a variety of mechanisms in inflammatory disease, the mutual activation of
      platelets and neutrophils may augment host defense.

PMID- 27714786
TI  - Transfer Frequency as a Measure of Hospital Capability and Regionalization.
AB  - OBJECTIVE: To provide metrics for quantifying the capability of hospitals and the
      degree of care regionalization. DATA SOURCE: Administrative database covering
      more than 10 million hospital encounters during a 3-year period (2012-2014) in
      Massachusetts. PRINCIPAL FINDINGS: We calculated the condition-specific
      probabilities of transfer for all acute care hospitals in Massachusetts and
      devised two new metrics, the Hospital Capability Index (HCI) and the
      Regionalization Index (RI), for analyzing hospital systems. The HCI had face
      validity, accurately differentiating academic, teaching, and community hospitals
      of varying size. Individual hospital capabilities were clearly revealed in
      "fingerprints" of their condition-specific transfer behavior. The RI also
      performed well, with those of specific conditions successfully quantifying the
      concentration of care arising from regulatory and public health activity. The
      median RI of all conditions within the Massachusetts health care system was 0.21
      (IQR, 0.13-0.36), with a long tail of conditions that were very highly
      regionalized. Application of the HCI and RI metrics together across the entire
      state identified the degree of interdependence among its hospitals. CONCLUSIONS:
      Condition-specific transfer activity, as captured in the HCI and RI, provides
      quantitative measures of hospital capability and regionalization of care.

PMID- 27714787
TI  - Integrins and heparan sulfate proteoglycans on hepatic stellate cells (HSC) are
      novel receptors for HSC-derived exosomes.
AB  - Exosomes mediate intercellular microRNA delivery between hepatic stellate cells
      (HSC), the principal fibrosis-producing cells in the liver. The purpose of this
      study was to identify receptors on HSC for HSC-derived exosomes, which bind to
      HSC rather than to hepatocytes. Our findings indicate that exosome binding to HSC
      is blocked by treating HSC with RGD, EDTA, integrin alphav or beta1 siRNAs,
      integrin alphavbeta3 or alpha5beta1 neutralizing antibodies, heparin, or sodium
      chlorate. Furthermore, exosome cargo delivery and exosome-regulated functions in
      HSC, including expression of fibrosis- or activation-associated genes and/or miR
      214 target gene regulation, are dependent on cellular integrin alphavbeta3,
      integrin alpha5beta1, or heparan sulfate proteolgycans (HSPG). Thus, integrins
      and HSPG mediate the binding of HSC-derived exosomes to HSC as well as the
      delivery and intracellular action of the exosomal payload.

PMID- 27714788
TI  - A feasibility trial of an Internet-delivered and transdiagnostic cognitive
      behavioral therapy treatment program for anxiety, depression, and disability
      among adults with epilepsy.
AB  - OBJECTIVE: Anxiety and depression are highly prevalent in people with epilepsy
      (PWE) and contribute to increased disability. Unfortunately, there are numerous
      barriers (e.g., cost, distance, and stigma) and service gaps (e.g., lack of
      services and trained clinicians) that prevent many PWE from accessing traditional
      face-to-face psychological services. The aim of the present study was to examine
      the feasibility of a new transdiagnostic Internet-delivered cognitive behavioral
      therapy (iCBT) program, the Chronic Conditions Course, to simultaneously treat
      symptoms of anxiety, depression, and disability. METHODS: A single-group
      feasibility open trial was employed involving 27 adults with epilepsy. The
      program comprises five online lessons delivered over 8 weeks and is provided with
      weekly contact from a mental health professional via e-mail and telephone.
      RESULTS: High treatment completion rates and levels of satisfaction were
      reported. Evidence of significant improvements in our primary outcomes (within
      group Cohen's d [d]; average [avg.] reductions) of anxiety (d >= 1.28; avg.
      reduction >= 54%), depression (d >= 1.24; avg. reduction >= 54%), epilepsy
      specific depression (d >= 0.95; avg. reduction >= 35%), and disability (d >=
      0.62; avg. reduction >= 33%) were observed at posttreatment, which were sustained
      at or further improved to 3-month follow-up. On our secondary outcomes there were
      significant improvements for life satisfaction (d >= 0.70; avg. improvement >=
      26%) but not for perceived cognitive difficulties (d >= 0.48; avg. reduction >=
      15%). Highlighting the potential of the approach, relatively little clinician
      time was required per participant (mean 80.62 min, standard deviation [SD]
      54.78), and the trial involved a broad range of geographically dispersed
      patients. SIGNIFICANCE: The findings of the current study support the feasibility
      and potential of transdiagnostic Internet-delivered treatments for adults with
      epilepsy. Further large-scale controlled trials are warranted.

PMID- 27714789
TI  - Substrate profiling of Zika virus NS2B-NS3 protease.
AB  - Zika virus (ZIKV), isolated from macaques in Uganda in 1947, was not considered
      to be a dangerous human pathogen. However, this view has recently changed as ZIKV
      infections are now associated with serious pathological disorders including
      microcephaly and Guillain-Barre syndrome. Similar to other viruses in the
      Flaviviridae family, ZIKV expresses the serine protease NS3 which is responsible
      for viral protein processing and replication. Herein, we report the expression of
      an active NS3pro domain fused with the NS2B cofactor (NS2BLN NS3pro ) in a
      prokaryotic expression system and profile its specificity for synthesized FRET
      type substrate libraries. Our findings pave way for screening potential
      intracellular substrates of NS3 and for developing specific inhibitors of this
      ZIKV protease.

PMID- 27714792
TI  - Quality and safety in adult epilepsy monitoring units: A systematic review and
      meta-analysis.
AB  - OBJECTIVE: The epilepsy monitoring unit (EMU) is a valuable resource for
      optimizing management of persons with epilepsy, but may place patients at risk
      for adverse events due to withdrawal of treatment and induction of symptoms. The
      purpose of this study was to synthesize data on the safety and quality of care in
      EMUs to inform the development of quality indicators for EMUs. METHODS: A
      systematic review was conducted according to the Preferred Reporting and Items
      for Systematic Review and Meta-Analysis (PRISMA) statement. The search strategy,
      which included broad search terms and synonyms pertaining to the EMU, was run in
      six medical databases and included conference proceedings. Data abstracted
      included patient and EMU demographics and quality and safety variables. Study
      quality was evaluated using a modified 15-item Strengthening the Reporting of
      Observational Studies in Epidemiology (STROBE) checklist. Descriptive statistics
      and meta-analyses were used to describe and synthesize the evidence. RESULTS: The
      search yielded 7,601 references, of which 604 were reviewed in full text. One
      hundred thirty-five studies were included. The quality and safety data came from
      181,823 patients and reported on 34 different quality and safety variables.
      Included studies commonly reported the number of patients (108 studies; median
      number patients, 171.5), age (49 studies; mean age 35.7 years old), and the
      reason for admission (34 studies). The most common quality and safety data
      reported were the utility of the EMU admission (38 studies). Thirty-three studies
      (24.4%) reported on adverse events, and yielded a pooled proportion of adverse
      events of 7% (95% confidence interval [CI] 5-9%). The mean quality score was
      73.3% (standard deviation [SD] 17.2). SIGNIFICANCE: This study demonstrates that
      there is a great deal of variation in the reporting of quality and safety
      measures and in the quality and safety in EMUs. Study quality also varied
      considerably from one study to the next. These findings highlight the need to
      develop evidence-based, consensus-driven quality indicators for EMUs.

PMID- 27714791
TI  - Misclassification Risk of Tier-Based Physician Quality Performance Systems.
AB  - OBJECTIVE: There is increasing interest in identifying high-quality physicians,
      such as whether physicians perform above or below a threshold level. To evaluate
      whether current methods accurately distinguish above- versus below-threshold
      physicians, we estimate misclassification rates for two-category identification
      systems. DATA SOURCES: Claims data for Medicare fee-for-service beneficiaries
      residing in Florida or New York in 2010. STUDY DESIGN: Estimate colorectal
      cancer, glaucoma, and diabetes quality scores for 23,085 physicians. Use a beta
      binomial model to estimate physician score reliabilities. Compute the proportion
      of physicians whose performance tier would be misclassified under three scoring
      systems. PRINCIPAL FINDINGS: In the three scoring systems, misclassification
      ranges were 8.6-25.7 percent, 6.4-22.8 percent, and 4.5-21.7%. True positive rate
      ranges were 72.9-97.0 percent, 83.4-100.0 percent, and 34.7-88.2 percent. True
      negative rate ranges were 68.5-91.6 percent, 10.5-92.4 percent, and 81.1-99.9
      percent. Positive predictive value ranges were 70.5-91.6 percent, 77.0-97.3
      percent, and 55.2-99.1 percent. CONCLUSIONS: Current methods for profiling
      physicians on quality may produce misleading results, as the number of eligible
      events is typically small. Misclassification is a policy-relevant measure of the
      potential impact of tiering on providers, payers, and patients. Quantifying
      misclassification rates should inform the construction of high-performance
      networks and quality improvement initiatives.

PMID- 27714793
TI  - Genetic drift and mutational hazard in the evolution of salamander genomic
      gigantism.
AB  - Salamanders have the largest nuclear genomes among tetrapods and, excepting
      lungfishes, among vertebrates as a whole. Lynch and Conery (2003) have proposed
      the mutational-hazard hypothesis to explain variation in genome size and
      complexity. Under this hypothesis, noncoding DNA imposes a selective cost by
      increasing the target for degenerative mutations (i.e., the mutational hazard).
      Expansion of noncoding DNA, and thus genome size, is driven by increased levels
      of genetic drift and/or decreased mutation rates; the former determines the
      efficiency with which purifying selection can remove excess DNA, whereas the
      latter determines the level of mutational hazard. Here, we test the hypothesis
      that salamanders have experienced stronger long-term, persistent genetic drift
      than frogs, a related clade with more typically sized vertebrate genomes. To test
      this hypothesis, we compared dN/dS and Kr/Kc values of protein-coding genes
      between these clades. Our results do not support this hypothesis; we find that
      salamanders have not experienced stronger genetic drift than frogs. Additionally,
      we find evidence consistent with a lower nucleotide substitution rate in
      salamanders. This result, along with previous work showing lower rates of small
      deletion and ectopic recombination in salamanders, suggests that a lower
      mutational hazard may contribute to genomic gigantism in this clade.

PMID- 27714790
TI  - TeloPCR-seq: a high-throughput sequencing approach for telomeres.
AB  - We have developed a high-throughput sequencing approach that enables us to
      determine terminal telomere sequences from tens of thousands of individual
      Schizosaccharomyces pombe telomeres. This method provides unprecedented coverage
      of telomeric sequence complexity in fission yeast. S. pombe telomeres are
      composed of modular degenerate repeats that can be explained by variation in
      usage of the TER1 RNA template during reverse transcription. Taking advantage of
      this deep sequencing approach, we find that 'like' repeat modules are highly
      correlated within individual telomeres. Moreover, repeat module preference varies
      with telomere length, suggesting that existing repeats promote the incorporation
      of like repeats and/or that specific conformations of the telomerase holoenzyme
      efficiently and/or processively add repeats of like nature. After the loss of
      telomerase activity, this sequencing and analysis pipeline defines a population
      of telomeres with altered sequence content. This approach will be adaptable to
      study telomeric repeats in other organisms and also to interrogate repetitive
      sequences throughout the genome that are inaccessible to other sequencing
      methods.

PMID- 27714794
TI  - Pubertal pair-housing facilitates adult sexual behavior in male rats.
AB  - This study examined the effects of pubertal testosterone (T) and social housing
      manipulations on male sexual behavior in adult rats. Prepubertal rats were
      castrated at 21 days of age (P21) and implanted with either blank or T-releasing
      pellets. At the onset of puberty, P28, half the rats in each treatment group were
      either single- or pair-housed with a male of the same hormone condition through
      P56, at which time pellets were removed and all rats were single-housed. In
      adulthood (P84), all rats received T replacement and were tested for sexual
      behavior. Rats pair-housed during adolescence showed more sexual behavior and
      greater improvement of sexual performance over repeated tests than single-housed
      rats, regardless of pubertal T status. Pubertal T, however, did facilitate the
      frequency of anogenital investigation. Thus, in male rats, social interactions
      during adolescence are more important than exposure to pubertal T in enhancing
      adult sexual behavior.

PMID- 27714795
TI  - Experimental insights on the function of ancillary pollen and stigma
      polymorphisms in plants with heteromorphic incompatibility.
AB  - Most heterostylous plants possess a reciprocal arrangement of stigmas and anthers
      (reciprocal herkogamy), heteromorphic self-incompatibility, and ancillary
      polymorphisms of pollen and stigmas. The topographical complementarity hypothesis
      proposes that ancillary polymorphisms function in the rejection of incompatible
      pollen thus promoting disassortative pollination. Here, we test this hypothesis
      by investigating patterns of pollen transfer and capture in populations of
      dimorphic Armeria maritima and A. pubigera and distylous Limonium vulgare
      (Plumbaginaceae), and by studying pollen adherence and germination patterns in A.
      maritima following controlled hand-pollinations. Armeria lacks reciprocal
      herkogamy allowing the evaluation of the extent to which ancillary polymorphisms
      affect the composition of pollen loads. We compared the amounts of compatible and
      incompatible pollen on stigmas in natural populations and calculated the
      proficiencies of pollen transfer for each mating type. We detected disassortative
      pollination in each species, and mating types did not differ in compatible pollen
      capture, although cob stigmas captured more incompatible pollen. Controlled hand
      pollinations revealed the failure of incompatible pollen to adhere and germinate
      on stigmas. Our results provided evidence that, while structural in nature,
      pollen-stigma dimorphisms are tightly associated with heteromorphic
      incompatibility and likely function to promote disassortative pollination,
      especially in the absence of reciprocal herkogamy.

PMID- 27714797
TI  - Structural insights into the interaction of human p97 N-terminal domain and SHP
      motif in Derlin-1 rhomboid pseudoprotease.
AB  - The interaction of the rhomboid pseudoprotease Derlin-1 and p97 is crucial for
      the retrotranslocation of polyubiquitinated substrates in the endoplasmic
      reticulum-associated degradation pathway. We report a 2.25 A resolution structure
      of the p97 N-terminal domain (p97N) in complex with the Derlin-1 SHP motif.
      Remarkably, the SHP motif adopts a short, antiparallel beta-strand that interacts
      with the beta-sheet of p97N-a site distinct from that to which most p97 adaptor
      proteins bind. Mutational and biochemical analyses contributed to defining the
      specific interaction, demonstrating the importance of a highly conserved binding
      pocket on p97N and a signature motif on SHP. Our findings may also provide
      insights into the interactions between other SHP-containing proteins and p97N.

PMID- 27714796
TI  - Genomic imprinting, disrupted placental expression, and speciation.
AB  - The importance of regulatory incompatibilities to the early stages of speciation
      remains unclear. Hybrid mammals often show extreme parent-of-origin growth
      effects that are thought to be a consequence of disrupted genetic imprinting
      (parent-specific epigenetic gene silencing) during early development. Here, we
      test the long-standing hypothesis that abnormal hybrid growth reflects disrupted
      gene expression due to loss of imprinting (LOI) in hybrid placentas, resulting in
      dosage imbalances between paternal growth factors and maternal growth repressors.
      We analyzed placental gene expression in reciprocal dwarf hamster hybrids that
      show extreme parent-of-origin growth effects relative to their parental species.
      In massively enlarged hybrid placentas, we observed both extensive transgressive
      expression of growth-related genes and biallelic expression of many genes that
      were paternally silenced in normal sized hybrids. However, the apparent
      widespread disruption of paternal silencing was coupled with reduced gene
      expression levels overall. These patterns are contrary to the predictions of the
      LOI model and indicate that hybrid misexpression of dosage-sensitive genes is
      caused by other regulatory mechanisms in this system. Collectively, our results
      support a central role for disrupted gene expression and imprinting in the
      evolution of mammalian hybrid inviability, but call into question the generality
      of the widely invoked LOI model.

PMID- 27714798
TI  - The "when" and the "where" of single-trial allocentric spatial memory performance
      in young children: Insights into the development of episodic memory.
AB  - Allocentric spatial memory, "where" with respect to the surrounding environment,
      is one of the three fundamental components of episodic memory: what, where, when.
      Whereas basic allocentric spatial memory abilities are reliably observed in
      children after 2 years of age, coinciding with the offset of infantile amnesia,
      the resolution of allocentric spatial memory acquired over repeated trials
      improves from 2 to 4 years of age. Here, we first show that single-trial
      allocentric spatial memory performance improves in children from 3.5 to 7 years
      of age, during the typical period of childhood amnesia. Second, we show that
      large individual variation exists in children's performance at this age. Third,
      and most importantly, we show that improvements in single-trial allocentric
      spatial memory performance are due to an increasing ability to spatially and
      temporally separate locations and events. Such improvements in spatial and
      temporal processing abilities may contribute to the gradual offset of childhood
      amnesia.

PMID- 27714799
TI  - Can a More User-Friendly Medicare Plan Finder Improve Consumers' Selection of
      Medicare Plans?
AB  - OBJECTIVE: To evaluate the efficacy for consumers of two potential enhancements
      to the Medicare Plan Finder (MPF)-a simplified data display and a "quick links"
      home page designed to match the specific tasks that users seek to accomplish on
      the MPF. DATA SOURCES/STUDY SETTING: Participants (N = 641) were seniors and
      adult caregivers of seniors who were recruited from a national online panel.
      Participants browsed a simulated version of the MPF, made a hypothetical plan
      choice, and reported on their experience. STUDY DESIGN: Participants were
      randomly assigned to one of eight conditions in a fully factorial design: 2 home
      pages (quick links, current MPF home page) * 2 data displays (simplified, current
      MPF display) * 2 plan types (stand-alone prescription drug plan [PDP], Medicare
      Advantage plan with prescription drug coverage [MA-PD]). PRINCIPAL FINDINGS: The
      quick links page resulted in more favorable perceptions of the MPF, improved
      users' understanding of the information, and increased the probability of
      choosing the objectively best plan. The simplified data display resulted in a
      more favorable evaluation of the website, better comprehension of the displayed
      information, and, among those choosing a PDP only, an increased probability of
      choosing the best plan. CONCLUSIONS: Design enhancements could markedly improve
      average website users' understanding, ability to use, and experience of using the
      MPF.

PMID- 27714801
TI  - An updated structural classification of substrate-binding proteins.
AB  - Substrate-binding proteins (SBPs) play an important role in solute uptake and
      signal transduction. In 2010, Berntsson et al. classified the 114 organism
      specific SBP structures available at that time and defined six protein clusters,
      based on their structural similarity. Since then, the number of unique SBP
      structures has increased almost fivefold, whereas the number of protein entries
      in the Protein Data Bank (PDB) nearly doubled. On the basis of the much larger
      dataset, we now subclassify the SBPs within the original clusters. Moreover, we
      propose a 7th cluster based on a small group of SBPs with structural features
      significantly different from those observed in the other proteins.

PMID- 27714800
TI  - Sustained User Engagement in Health Information Technology: The Long Road from
      Implementation to System Optimization of Computerized Physician Order Entry and
      Clinical Decision Support Systems for Prescribing in Hospitals in England.
AB  - OBJECTIVE: To explore and understand approaches to user engagement through
      investigating the range of ways in which health care workers and organizations
      accommodated the introduction of computerized physician order entry (CPOE) and
      computerized decision support (CDS) for hospital prescribing. STUDY SETTING: Six
      hospitals in England, United Kingdom. STUDY DESIGN: Qualitative case study. DATA
      COLLECTION: We undertook qualitative semi-structured interviews, non-participant
      observations of meetings and system use, and collected organizational documents
      over three time periods from six hospitals. Thematic analysis was initially
      undertaken within individual cases, followed by cross-case comparisons. FINDINGS:
      We conducted 173 interviews, conducted 24 observations, and collected 17
      documents between 2011 and 2015. We found that perceived individual and safety
      benefits among different user groups tended to facilitate engagement in some,
      while other less engaged groups developed resistance and unsanctioned workarounds
      if systems were perceived to be inadequate. We identified both the opportunity
      and need for sustained engagement across user groups around system enhancement
      (e.g., through customizing software) and the development of user competencies and
      effective use. CONCLUSIONS: There is an urgent need to move away from an episodic
      view of engagement focused on the preimplementation phase, to more continuous
      holistic attempts to engage with and respond to end-users.

PMID- 27714802
TI  - Persistent and Repetitive Visual Disturbances in Migraine: A Review.
AB  - Visual disturbances in migraineurs, such as visual aura, are typically episodic,
      that is, associated with the headache attack, and overlaid by head pain and other
      symptoms that impact the patient. In some patients, however, visual symptoms are
      dominant due to frequency (migraine aura status), duration (persistent migraine
      aura and other persistent positive visual phenomena), or complexity (visual snow
      syndrome). These syndromes are more rare and challenging to classify in clinical
      practice resulting in a lack of systematic studies on pathophysiology and
      treatment. We aim at describing clinical features and pathophysiological concepts
      of typical migraine aura with a focus on cortical spreading depression and
      differentiation from non-typical migraine aura. Additionally, we discuss
      nomenclature and the specifics of migraine aura status, persistent migraine aura,
      persistent positive visual phenomena, visual snow, and other migrainous visual
      disturbances. The term migraine with prolonged aura might be a useful bridge
      between typical aura and persistent aura. Further studies would be necessary to
      assess whether a return of the classification category eventually helps
      diagnosing or treating patients more effectively. A practical approach is
      presented to help the treating physician to assign the correct diagnosis and to
      choose a medication for treatment that has been successful in case reports of
      these rare but disabling conditions.

PMID- 27714803
TI  - Production and characterization of cowpea protein hydrolysate with optimum
      nitrogen solubility by enzymatic hydrolysis using pepsin.
AB  - BACKGROUND: Cowpea is a source of low-cost and good nutritional quality protein
      for utilization in food formulations in replacement of animal proteins. Therefore
      it is necessary that cowpea protein exhibits good functionality, particularly
      protein solubility which affects the other functional properties. The objective
      of this study was to produce cowpea protein hydrolysate exhibiting optimum
      solubility by the adequate combination of hydrolysis parameters, namely time,
      solid/liquid ratio (SLR) and enzyme/substrate ratio (ESR), and to determine its
      functional properties and molecular characteristics. RESULTS: A Box-Behnken
      experimental design was used for the experiments, and a second-order polynomial
      to model the effects of hydrolysis time, SLR and ESR on the degree of hydrolysis
      and nitrogen solubility index. The optimum hydrolysis conditions of time 208.61
      min, SLR 1/15 (w/w) and ESR 2.25% (w/w) yielded a nitrogen solubility of 75.71%.
      Protein breakdown and the peptide profile following enzymatic hydrolysis were
      evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and size
      exclusion chromatography. Cowpea protein hydrolysate showed higher oil absorption
      capacity, emulsifying activity and foaming ability compared with the concentrate.
      CONCLUSION: The solubility of cowpea protein hydrolysate was adequately optimized
      by response surface methodology, and the hydrolysate showed adequate
      functionality for use in food. (c) 2016 Society of Chemical Industry.

PMID- 27714804
TI  - OB or Not OB: Idiosyncratic utilization of the tRNA-binding OB-fold domain in
      unicellular, pathogenic eukaryotes.
AB  - In this review, we examine the so-called OB-fold, a tRNA-binding domain
      homologous to the bacterial tRNA-binding protein Trbp111. We highlight the
      ability of OB-fold homologs to bind tRNA species and summarize their distribution
      in evolution. Nature has capitalized on the advantageous effects acquired when an
      OB-fold domain binds to tRNA by evolutionarily selecting this domain for fusion
      to different enzymes. Here, we review our current understanding of how the
      complexity of OB-fold-containing proteins and enzymes developed to expand their
      functions, especially in unicellular, pathogenic eukaryotes.

PMID- 27714806
TI  - miR-296 inhibits proliferation and induces apoptosis by targeting FGFR1 in human
      hepatocellular carcinoma.
AB  - MiR-296 was previously reported to be underexpressed in hepatocellular carcinoma
      (HCC). However, the clinical value of miR-296 and its function in HCC remain
      poorly understood. In this study, we found that miR-296 levels are decreased in
      HCC specimens and cells, and that the underexpression of miR-296 is associated
      with adverse clinical parameters and poor overall survival rate. In vitro
      experiments indicate that miR-296 inhibits proliferation, colony formation, and
      cell cycle progression, and enhances apoptosis in HCC cells. Notably, we found
      that the fibroblast growth factor receptor 1 (FGFR1) is a downstream target that
      mediates the functions of miR-296 in HCC. Thus, our findings indicate that miR
      296 exerts a tumor suppressive role in HCC and is a potential biomarker and drug
      target.

PMID- 27714805
TI  - Challenging of AS160/TBC1D4 Alters Intracellular Lipid milieu in L6 Myotubes
      Incubated With Palmitate.
AB  - The Akt substrate of 160 kDa (AS160) is a key regulator of GLUT4 translocation
      from intracellular depots to the plasma membrane in myocytes. Likely, AS160 also
      controls LCFAs transport, which requires relocation of fatty acid transporters.
      The aim of the present study was to determine the impact of AS160 knockdown on
      lipid milieu in L6 myotubes incubated with palmitate (PA). Therefore, we compared
      two different settings, namely: 1) AS160 knockdown prior to palmitate incubation
      (pre-PA-silencing, AS160- /PA); 2) palmitate incubation with subsequent AS160
      knockdown (post-PA-silencing, PA/AS160- ). The efficiency of AS160 silencing was
      checked at mRNA and protein levels. The expression and localization of FA
      transporters were determined using Western Blot and immunofluorescence analyses.
      Intracellular lipid content (FFA, DAG, TAG, and PL) and FA composition were
      estimated by GLC, whereas basal palmitate uptake was analyzed by means of
      scintigraphy. Both groups with silenced AS160 were characterized by a greater
      expression of FA transporters (FAT/CD36, FATP-1, 4) which had contributed to an
      increased FA cellular influx. Accordingly, we observed that post-PA-silencing of
      AS160 resulted in a marked decrement in DAG, TAG, and PL contents, but increased
      FFA content (PA/AS160- vs. PA). The opposite effect was observed in the group
      with pre-PA-silencing of AS160 in which AS160 knockdown did not affect the lipid
      pools (AS160- /PA vs. PA). Our results indicate that post-PA-silencing of AS160
      has a capacity to decrease the lipotoxic effect(s) of PA by decreasing the
      content of lipids (DAG and PL) that promote insulin resistance in myotubes. J.
      Cell. Physiol. 232: 2373-2386, 2017. (c) 2016 The Authors. Journal of Cellular
      Physiology Published by Wiley Periodicals Inc.

PMID- 27714807
TI  - Tiny estimates of the Ne /N ratio in marine fishes: Are they real?
AB  - Theory and empirical estimates agree that the ratio of effective size (Ne ) to
      census size (N) falls roughly in the range 0.1-0.5 for most populations. In a
      number of marine species, however, genetic estimates of contemporary Ne /N are as
      much as 5-6 orders of magnitude lower. Although some mechanisms that could
      produce such tiny Ne /N ratios have been proposed, the subject remains
      controversial. This issue is important to resolve: if Ne /N can be 10-3 or
      smaller, marine fish populations that are quite large could be at genetic risk.
      Based on a recently-improved understanding of factors that influence Ne and Ne /N
      in species with overlapping generations, this paper evaluates conditions
      necessary to produce tiny Ne /N ratios in actual populations. These analyses show
      that although increased longevity, fecundity and variance in reproductive success
      that increase with age, and increased egg quality with age [the big old fat
      fecund female fish (BOFFFF) hypothesis] all reduce Ne /N, extreme scenarios are
      required to reduce Ne /N below about 0.01. Therefore, tiny Ne /N ratios require
      some version of Hedgecock's 'sweepstakes' hypothesis, whereby only a few families
      reproduce successfully. Simulations using common genetically-based estimators
      show that, when true Ne is very large (>=106 ), a substantial fraction of point
      estimates of Ne /N can be 10-3 or smaller. These results mean that tiny,
      genetically-based point estimates of Ne /N in large marine populations are
      expected to be quite common, even when the true Ne /N ratio is 'normal' (~0.1 or
      higher). Very large samples of individuals can reduce, but not eliminate, this
      problem. The simulation results also emphasize the importance of considering
      deviations from model assumptions (e.g. non-random sampling; weak selection or
      migration) that may be relatively small (and hence can generally be ignored when
      the signal is strong) but can lead to substantial biases when the drift signal is
      weak, as is likely for large marine populations. Empirical studies of this topic
      need to be able to distinguish between episodes of sweepstakes reproductive
      success that are ephemeral and lead to chaotic genetic patchiness, and those that
      are consistent enough across space and time to produce persistent evolutionary
      consequences.

PMID- 27714808
TI  - Subtle genetic population structure in Pacific halibut Hippoglossus stenolepis.
AB  - Pacific halibut Hippoglossus stenolepis from 10 sampling locations throughout
      their range were investigated for signs of population structure. Two genetic data
      sets were created: (1) all individuals (n = 828) at few anonymous microsatellite
      markers (number of loci = 16); (2) fewer individuals (n = 435) genotyped at
      anonymous as well as expressed sequence-tag linked microsatellites (number of
      loci = 61). A combination of multidimensional scaling plots, discriminant
      analysis of principal components and pairwise differentiation estimates suggested
      that samples from the Aleutian Islands, particularly the western Aleutian
      Islands, were genetically distinct from samples collected in other regions. In
      addition, outlier analyses found that two markers linked to expressed sequence
      tags may be under directional selection and could explain the differentiation
      among samples. These results confirm findings from previous research and suggest
      that population structure may exist within a current management unit (i.e.
      International Pacific Halibut Commission Regulatory Area 4B).

PMID- 27714809
TI  - Physical compatibility of total parenteral nutrition and drugs in Y-site
      administration to children from neonates to adolescents.
AB  - OBJECTIVES: Infusion of precipitate or destabilized emulsion can be harmful. The
      purpose of this study was to obtain Y-site compatibility data on intravenous
      drugs and total parenteral nutrition (TPN) relevant for children. METHODS: Two
      three-in-one TPN admixtures (Olimel N5E and Numeta G16E) used for children of
      different age groups were tested with ten drugs (ampicillin, ceftazidime,
      clindamycin, dexamethasone, fluconazole, fosphenytoin, furosemide, metronidazole,
      ondansetron and paracetamol). Drug : TPN ratios were estimated from a wide range
      of age and weight classes, and the most extreme mixing ratios (drug > TPN, TPN >
      drug) in addition to 1 + 1 were chosen. Assessment of potential precipitation was
      performed by subvisual particle counting, visual examinations and measurements of
      turbidity and pH. Emulsion stability was investigated by estimation of percentage
      of droplets above 5 MUm (PFAT5), mean droplet diameter and pH measurements.
      Complimentary theoretical evaluations were performed. KEY FINDINGS: Ampicillin,
      fosphenytoin and furosemide precipitated when mixed with TPN. The results for
      ceftazidime, clindamycin, dexamethasone, fluconazole, metronidazole, ondansetron
      and paracetamol suggest that they were compatible with either TPN in the tested
      concentrations. None of the drugs were found to destabilize the emulsions.
      CONCLUSION: Three drugs showed clear signs of precipitation when mixed with TPN
      and these products should not be co-administered in the same infusion line.

PMID- 27714811
TI  - Inhibitory Effects of Quercetin on Progression of Human Choriocarcinoma Cells Are
      Mediated Through PI3K/AKT and MAPK Signal Transduction Cascades.
AB  - As a major dietary flavonol, quercetin mitigates proliferation and progression of
      cancer due to its anti-angiogenic, anti-inflammatory, anti-oxidant, and apoptotic
      biological effects on cells. Although its apoptotic effects have been reported
      for various cancers, little is known of the functional role of quercetin in
      gestational choriocarcinoma. Results of the present study indicated that
      quercetin reduced proliferation and induced cell death in two choriocarcinoma
      cell lines, JAR and JEG3 cells, with an increase in the sub-G1 phase of the cell
      cycle. In addition, quercetin induced mitochondrial dysfunction significantly
      reduced mitochondrial membrane potential (MMP) and increased production of
      reactive oxygen species (ROS) in both JAR and JEG3 cells. Further, quercetin
      inhibited phosphorylation of AKT, P70S6K and S6 proteins whereas, it increased
      phosphorylation of ERK1/2, P38, JNK and P90RSK proteins in JAR and JEG3 cells.
      The decrease in viability of choriocarcinoma cells treated with quercetin was
      confirmed by using combinations of quercetin and pharmacological inhibitors of
      the PI3K and MAPK signaling pathways. Classical chemotherapeutic agents,
      cisplatin (a platinum-based drug) and paclitaxel (a taxene-based drug), inhibited
      proliferation of JAR and JEG3 cells, and when combined with quercetin, the
      antiproliferative effects of cisplatin and paclitaxel were enhanced for both
      choriocarcinoma cell lines. Collectively, these results suggest that quercetin
      prevents development of choriocarcinoma and may be a valuable therapeutic agent
      for treatment of choriocarcinoma through its regulation of PI3K and MAPK signal
      transduction pathways. J. Cell. Physiol. 232: 1428-1440, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27714810
TI  - Essential Role of CFTR in PKA-Dependent Phosphorylation, Alkalinization, and
      Hyperpolarization During Human Sperm Capacitation.
AB  - Mammalian sperm require to spend a limited period of time in the female
      reproductive tract to become competent to fertilize in a process called
      capacitation. It is well established that HCO3- is essential for capacitation
      because it activates the atypical soluble adenylate cyclase ADCY10 leading to
      cAMP production, and promotes alkalinization of cytoplasm, and membrane
      hyperpolarization. However, how HCO3- is transported into the sperm is not well
      understood. There is evidence that CFTR activity is involved in the human sperm
      capacitation but how this channel is integrated in the complex signaling cascades
      associated with this process remains largely unknown. In the present work, we
      have analyzed the extent to which CFTR regulates different events in human sperm
      capacitation. We observed that inhibition of CFTR affects HCO3- -entrance
      dependent events resulting in lower PKA activity. CFTR inhibition also affected
      cAMP/PKA-downstream events such as the increase in tyrosine phosphorylation,
      hyperactivated motility, and acrosome reaction. In addition, we demonstrated for
      the first time, that CFTR and PKA activity are essential for the regulation of
      intracellular pH, and membrane potential in human sperm. Addition of permeable
      cAMP partially recovered all the PKA-dependent events altered in the presence of
      inh-172 which is consistent with a role of CFTR upstream of PKA activation. J.
      Cell. Physiol. 232: 1404-1414, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27714812
TI  - Dact1, a Wnt-Pathway Inhibitor, Mediates Human Mesangial Cell TGF-beta1-Induced
      Apoptosis.
AB  - Chronic kidney disease (CKD) is a worldwide public health problem that affects
      millions of men and women of all ages and racial groups. Loss of mesangial cells
      (MC) represents an early common feature in the pathogenesis of CKD. Transforming
      growth factor-beta1 (TGF-beta1) is a key inducer of kidney damage and triggers
      several pathological changes in renal cells, notably MC apoptosis. However, the
      mechanism of MC apoptosis induced by TGF-beta1 remains elusive. Here, we
      demonstrate for the first time a novel regulatory pathway in which the disheveled
      binding antagonist of beta-catenin 1 (Dact1) gene is upregulated by TGF-beta1,
      inducing MC apoptosis. We also show that the inhibitory effect of Dact1 and TGF
      beta1 on the transcriptional activation of the pro-survival Wnt pathway is the
      mechanism of death induction. In addition, Dact1 mRNA/protein levels are
      increased in kidney remnants from 5/6 nephrectomized rats and strongly correlate
      with TGF-beta1 expression. Together, our results point to Dact1 as a novel
      element controlling MC survival that is causally related to CKD progression. J.
      Cell. Physiol. 232: 2104-2111, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27714813
TI  - Propolis modulates miRNAs involved in TLR-4 pathway, NF-kappaB activation,
      cytokine production and in the bactericidal activity of human dendritic cells.
AB  - OBJECTIVES: Dendritic cells (DCs) are antigen-presenting cells, essential for
      recognition and presentation of pathogens to T cells. Propolis, a resinous
      material produced by bees from various plants, exhibits numerous biological
      properties, highlighting its immunomodulatory action. Here, we assayed the
      effects of propolis on the maturation and function of human DCs. METHODS: DCs
      were generated from human monocytes and incubated with propolis and LPS. NF
      kappaB and cytokines production were determined by ELISA. microRNA's expression
      was analysed by RT-qPCR and cell markers detection by flow cytometry. Colony
      forming units were obtained to assess the bactericidal activity of propolis
      treated DCs. KEY FINDINGS: Propolis activated DCs in the presence of LPS,
      inducing NF-kB, TNF-alpha, IL-6 and IL-10 production. The inhibition of hsa-miR
      148a and hsa-miR-148b abolished the inhibitory effects on HLA-DR and pro
      inflammatory cytokines. The increased expression of hsa-miR-155 may be correlated
      to the increase in TLR-4 and CD86 expression, maintaining LPS-induced expression
      of HLA-DR and CD40. Such parameters may be involved in the increased bactericidal
      activity of DCs against Streptococcus mutans. CONCLUSION: Propolis modulated the
      maturation and function of DCs and may be useful in the initial steps of the
      immune response, providing a novel approach to the development of DC-based
      strategies and for the discovery of new immunomodulators.

PMID- 27714814
TI  - Genetic Identification of Communist Crimes' Victims (1944-1956) Based on the
      Analysis of One of Many Mass Graves Discovered on the Powazki Military Cemetery
      in Warsaw, Poland.
AB  - As the result of the communist terror in Poland, during years 1944-1956 more than
      50,000 people died. Their bodies were buried secretly, and most places are still
      unknown. The research presents the results of identification of people buried in
      one of many mass graves, which were found at the cemetery Powazki Military in
      Warsaw, Poland. Exhumation revealed the remains of eight people, among which
      seven were identified genetically. Well-preserved molars were used for the study.
      Reference material was collected from the closest living relatives. In one case,
      an exhumation of victim's parents had to be performed. DNA from swabs was
      extracted with a PrepFiler(r) BTA Forensic DNA Extraction Kit and organic method.
      Autosomal, Y-STR amplification, and mtDNA sequencing were performed. The
      biostatistical calculations resulted in LR values from 1608 to 928 * 1018 . So
      far, remains of more than 50 victims were identified.

PMID- 27714815
TI  - Osteoclast Fusion: Time-Lapse Reveals Involvement of CD47 and Syncytin-1 at
      Different Stages of Nuclearity.
AB  - Investigations addressing the molecular keys of osteoclast fusion are primarily
      based on end-point analyses. No matter if investigations are performed in vivo or
      in vitro the impact of a given factor is predominantly analyzed by counting the
      number of multi-nucleated cells, the number of nuclei per multinucleated cell or
      TRAcP activity. But end-point analyses do not show how the fusion came about.
      This would not be a problem if fusion of osteoclasts was a random process and
      occurred by the same molecular mechanism from beginning to end. However, we and
      others have in the recent period published data suggesting that fusion partners
      may specifically select each other and that heterogeneity between the partners
      seems to play a role. Therefore, we set out to directly test the hypothesis that
      fusion factors have a heterogenic involvement at different stages of nuclearity.
      Therefore, we have analyzed individual fusion events using time-lapse and
      antagonists of CD47 and syncytin-1. All time-lapse recordings have been studied
      by two independent observers. A total of 1808 fusion events were analyzed. The
      present study shows that CD47 and syncytin-1 have different roles in osteoclast
      fusion depending on the nuclearity of fusion partners. While CD47 promotes cell
      fusions involving mono-nucleated pre-osteoclasts, syncytin-1 promotes fusion of
      two multi-nucleated osteoclasts, but also reduces the number of fusions between
      mono-nucleated pre-osteoclasts. Furthermore, CD47 seems to mediate fusion mostly
      through broad contact surfaces between the partners' cell membrane while syncytin
      1 mediate fusion through phagocytic-cup like structure. J. Cell. Physiol. 232:
      1396-1403, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27714816
TI  - Human cytomegalovirus infection promotes the stemness of U251 glioma cells.
AB  - Glioblastoma (GBM) are the most common and aggressive tumors of human brain.
      Recent studies showed that human cytomegalovirus (HCMV) can induce malignant
      transformation of tumor cells to maintain stemness. Transcription factor 5 (ATF5)
      is an anti-apoptotic protein that is highly expressed in malignant glioma. The
      aim of this study is to investigate the effect of HCMV infection on the stem cell
      makers of U251 cells. U251 cells were infected by AD169 HCMV strain (MOI = 1).
      The expression of stem cell makers (CD133, NES, Notch1) in infected U251 cells
      were compared with the expression in uninfected U251 cell to see the difference
      between them. Then, the changes of cell proliferation activity and the expression
      level of Notch intracellular domain (NICD), Notch1, ATF5, and IE protein were
      detected in the infected cells, and the expressions of Notch1 and NICD were
      increased. Cell proliferation assay showed that HCMV infection significantly
      increased the proliferation. These cells could form tumor spheres in non-adherent
      conditions. Consistent with these findings, the effect of silencing ATF5 on the
      proliferation of HCMV-infected U251 cells was also examined. The result shows
      that short interfering RNA-mediated ATF5 downregulation inhibited this process.
      These findings imply that HCMV infection may regulate ATF5 signaling pathway to
      increase cell malignant traits and maintain stemness. J. Med. Virol. 89:878-886,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27714817
TI  - Effect of solvent on retarding the release of diltiazem HCl from Polyox-based
      liquisolid tablets.
AB  - OBJECTIVES: The aim of this work was to investigate the use of liquisolid
      technique to sustain the release of a model highly soluble drug, diltiazem HCl,
      from liquisolid matrices containing Polyox, a recently proposed matrix-forming
      hydrophilic polymer as an alternative to hypromellose. METHODS: Polyox-based
      liquisolid formulations prepared using several non-volatile solvents (i.e.
      polysorbate 80, polyethylene glycol, polyethylene glycol 200 and polyethylene
      glycol 600) and then characterised using differential scanning calorimetry and
      powder X-ray diffraction. The influence of solvent on retarding the release of
      diltiazem HCl from Polyox-based liquisolid tablets compared to conventional
      physical mixture tablets was studied. KEY FINDINGS: Liquisolid tablets exhibited
      greater retarding properties compared to conventional tablets. The use of
      polysorbate produced a slower release pattern of the drug from diltiazem
      hydrochloride (DTZ) liquisolid tablets compared to propylene glycol and
      polyethylene glycol (200 and 600). The release retardation was decreased with the
      increase in the concentration of the drug within drug:solvent liquid medication
      used. Solid-state analysis suggested the presence of a fraction of the drug mass
      in a solubilised state within polysorbate in liquisolid powders. CONCLUSION:
      Polyox-based matrix tablets prepared using liquisolid technique in the presence
      of a carefully selected non-volatile solvent could produce desirable, more
      sustained release profiles of highly water-soluble drugs compared to conventional
      physical mixture tablets.

PMID- 27714818
TI  - Determination of norfloxacin in food by an enhanced spectrofluorimetric method.
AB  - BACKGROUND: Using a norfloxacin (NFLX)-Nd3+ -cetyltrimethylammonium bromide
      (CTAB) system for the detection of NFLX, a simple and sensitive method based on
      fluorescence enhancement was developed. RESULTS: In pH 7.0 buffer solution, NFLX
      reacted with Nd3+ to form a complex, which resulted in fluorescence enhancement
      of NFLX, and the maximum emission peak shifted from 415 nm for NFLX to 450 nm for
      NFLX-Nd3+ . Moreover, the fluorescence intensity increased further when the
      surfactant CTAB was added to NFLX-Nd3+ . Under the optimum conditions, the
      fluorescence intensity of the NFLX-Nd3+ -CTAB system was linearly correlated with
      the NFLX concentration in the range 0.038-10 umol L-1 , with a correlation
      coefficient (R2 ) of 0.9997. The detection limit (3sigma/k) was 0.021 umol L-1 ,
      indicating that this method can be applied to detect trace NFLX levels. The
      mechanism of fluorescence enhancement is discussed. The method was used to detect
      NFLX in fish and chicken samples with satisfactory results. CONCLUSION: The
      present results indicate that this method has the potential for fast and real
      time determination of NFLX in food samples (c) 2016 Society of Chemical Industry.

PMID- 27714819
TI  - Short- and Long-Term Hindlimb Immobilization and Reloading: Profile of Epigenetic
      Events in Gastrocnemius.
AB  - Skeletal muscle dysfunction and atrophy are characteristic features accompanying
      chronic conditions. Epigenetic events regulate muscle mass and function
      maintenance. We hypothesized that the pattern of epigenetic events (muscle
      enriched microRNAs and histone acetylation) and acetylation of transcription
      factors known to signal muscle wasting may differ between early- and late-time
      points in skeletal muscles of mice exposed to hindlimb immobilization (I) and
      recovery following I. Body and muscle weights, grip strength, muscle-enriched
      microRNAs, histone deacetylases (HDACs), acetylation of proteins, histones, and
      transcription factors (TF), myogenic TF factors, and muscle phenotype were
      assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15, and 30
      days, I groups) of hindlimb immobilization, and in those exposed to reloading for
      different periods of time (1, 3, 7, 15, and 30 days, R groups) following 7-day
      immobilization. Compared to non-immobilized controls, muscle weight, limb
      strength, microRNAs, especially miR-486, SIRT1 levels, and slow- and fast-twitch
      cross-sectional areas were decreased in mice of I groups, whereas Pax7 and
      acetylated FoxO1 and FoxO3 levels were increased. Muscle reloading following
      splint removal improved muscle mass loss, strength, and fiber atrophy, by
      increasing microRNAs, particularly miR-486, and SIRT1 content, while decreasing
      acetylated FoxO1 and FoxO3 levels. In this mouse model of disuse muscle atrophy,
      muscle-enriched microRNAs, especially miR-486, through Pax7 regulation delayed
      muscle cell differentiation following unloading of gastrocnemius muscle.
      Acetylation of FoxO1 and 3 seemed to drive muscle mass loss and atrophy, while
      deacetylation of these factors through SIRT1 would enable the muscle fibers to
      regenerate. J. Cell. Physiol. 232: 1415-1427, 2017. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27714820
TI  - Analysis of water and nitrogen use efficiency for maize (Zea mays L.) grown on
      soft rock and sand compound soil.
AB  - BACKGROUND: Maize was grown on compound soils constituted from mixtures of soft
      rock and sand at different ratios, and water use efficiency (WUE), nitrogen use
      efficiency (NUE) and fertilizer nitrogen use efficiency (FNUE) were quantified.
      The data were used to assist in designing strategies for optimizing water and
      nitrogen management practices for maize on the substrates used. Maize was sown in
      composite soil prepared at three ratios of soft rock and sand (1:1, 1:2 and 1:5
      v/v) in Mu Us Sandy Land, Yuyang district, Yulin city, China. Yields, amount of
      drainage, nitrogen (N) leaching, WUE and NUE were calculated. Then a water and
      nitrogen management model (WNMM) was calibrated and validated. RESULTS: No
      significant difference in evapotranspiration of maize was found among compound
      soils with soft rock/sand ratios of 1:1, 1:2 and 1:5, while water drainage
      increased significantly with increasing soft rock/sand ratio. WUE increased to
      1.30 kg m-3 in compound soil with 1:2 soft rock/sand ratio. Nitrogen leaching and
      ammonia volatilization were the main reason for nitrogen loss, and N reduction
      mainly relied on crop uptake. NUE and FNUE could reach 33.1 and 24.9 kg kg-1 N
      respectively. Water drainage and nitrogen leaching occurred mostly during heavy
      rainfall or irrigation. Through a scenario analysis of different rainfall types,
      water and fertilizer management systems were formulated each year. CONCLUSION:
      This study shows that soft rock plays a key role in improving the WUE, NUE and
      FNUE of maize. (c) 2016 Society of Chemical Industry.

PMID- 27714821
TI  - An association of type 1 diabetes mellitus with auditory dysfunction: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: To establish the relationship between the presence of type 1 diabetes
      mellitus (DM) and auditory dysfunction in clinical settings by a systematic
      review and meta-analysis of currently available published data. DATA SOURCES AND
      REVIEW METHODS: The electronic databases PubMed, Embase, and Wanfang Data were
      searched for eligible relevant studies up to May 2016, and the reference lists of
      the retrieved articles were used for additional manual search. All the articles
      included in this pooled analysis were determined according to the preset
      inclusion and exclusion criteria. Meta-analysis of pooled data was performed
      using Review Manager 5.3. RESULTS: A total of 15 studies were included for
      further combined analysis. The results showed that patients with type 1 diabetes
      had a significantly higher prevalence of hearing loss than controls (odds ratio =
      49.08, 95% confidence interval = 12.03-200.31, P < 0.00001); standardized mean of
      differences (SMD) of pure tone audiometry at 4,000 Hz between diabetes and
      controls was 0.87 (Z = 2.22, P = 0.03, I2 = 95%); SMD of the latency time was
      0.54 (Z = 2.69, P = 0.007, I2 = 78%) for waves III and 0.61 (Z = 2.38, P = 0.02,
      I2 = 86%) for wave V, respectively; and SMD of the interpeak latency time was
      0.41 (Z = 2.84, P = 0.005, I2 = 39%) for waves I to III and 0.61 (Z = 2.67, P =
      0.008, I2 = 81%) for waves I to V, respectively, between diabetics and controls.
      CONCLUSION: Our study reveals that there is relationship between the presence of
      type 1 DM and an increased risk for developing mild and subclinical hearing
      impairment. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:1689-1697, 2017.

PMID- 27714822
TI  - Biotechnological impact of stress response on wine yeast.
AB  - Wine yeast deals with many stress conditions during its biotechnological use.
      Biomass production and its dehydration produce major oxidative stress, while
      hyperosmotic shock, ethanol toxicity and starvation are relevant during grape
      juice fermentation. Most stress response mechanisms described in laboratory
      strains of Saccharomyces cerevisiae are useful for understanding the molecular
      machinery devoted to deal with harsh conditions during industrial wine yeast
      uses. However, the particularities of these strains themselves, and the media and
      conditions employed, need to be specifically looked at when studying protection
      mechanisms.

PMID- 27714823
TI  - Impact of the Pharmacy Practice Model Initiative on Clinical Pharmacy Specialist
      Practice: An Alternative Viewpoint.

PMID- 27714824
TI  - Quorum sensing influences phage infection efficiency via affecting cell
      population and physiological state.
AB  - Bacterial growth phase has been reported affecting phage infection. To underpin
      the related mechanism, infection efficiency of Pseudomonas aeruginosa phage K5 is
      characterized. When infecting the logarithmic cells, phage K5 produced
      significantly more infection centers than the stationary cells, well concordant
      with the viable cell ratio in the different growth phases. Additionally, the
      burst size decreased dramatically in the stationary cells, implying that the
      physiological state of the viable cells contributed to the productivity of phage
      K5, and it was consistent with the expression variation of the phage RNA
      polymerase. Quorum sensing inhibitor penicillic acid was applied and could
      significantly improve the viable cell proportion and the infection center
      numbers, but had less effect on the corresponding burst sizes. Moreover, the
      effect of penicillic acid and the quorum sensing regulator mutants on the
      production of phage C11 was also analyzed. Taken together, our data suggest that
      quorum sensing is involved in the defense of phage K5 infection by influencing
      the viable cell population and their physiological state, and it is an efficient
      and intrinsic pathway allowing bacteria to resist phage attacks in natural
      environment.

PMID- 27714825
TI  - Stress of algicidal substances from a bacterium Exiguobacterium sp. h10 on
      Microcystis aeruginosa.
AB  - : Microcystis aeruginosa is a cyanobacterial bloom-causing species and is
      considered a serious threat to human health and biological safety. In this study,
      the algicidal bacterium h10 showed high algicidal effects on M. aeruginosa 7820,
      and strain h10 was confirmed to belong to the genus Exiguobacterium, for which
      the name Exiguobacterium sp. h10 is proposed. Algicidal activity and mode
      analysis revealed that the supernatant, rather than the bacterial cells, was
      responsible for the algicidal activity, indicating that the algicidal mode of
      strain h10 is by indirect attack through the production of algicidal substances.
      Analysis of the algicidal substance characteristics showed a molecular weight of
      <1000 Da and that algicidal substances exhibit high thermal stability and pH
      instability, and the characteristic functional groups of the algicidal substance
      mainly included carbonyl, amino and hydroxyl groups. Under the effects of the
      algicidal substance, the cellular pigment content was significantly decreased,
      and the algal cell structure and morphology were seriously damaged. The results
      indicate that the algicidal bacterium Exiguobacterium sp. h10 could be a
      potential bio-agent for controlling cyanobacterial blooms of M. aeruginosa.
      SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, the effects of algicidal
      substances from an algicidal bacterium Exiguobacterium sp. h10 on the toxic
      cyanobacterium, Microcystis aeruginosa 7820, were first investigated. The
      algicidal mode of action was confirmed as an indirect attack through the
      production of algicidal substances. The characteristics of the algicidal
      substance were determined, especially the functional groups analysis that
      confirmed the algicidal substances were glycolipid mixtures. With the stress of
      algicidal substances, the algal chlorophyll a synthesis, cell structure and
      morphology were seriously damaged. This study proved that algicidal bacteria are
      promising sources of potential cyanobacterial bloom-control, and provided good
      procedures for the identification and analysis of an algicidal bacterium and
      substances.

PMID- 27714826
TI  - Multi-scale graph-cut algorithm for efficient water-fat separation.
AB  - PURPOSE: To improve the accuracy and robustness to noise in water-fat separation
      by unifying the multiscale and graph cut based approaches to B0 -correction.
      METHODS: A previously proposed water-fat separation algorithm that corrects for
      B0 field inhomogeneity in 3D by a single quadratic pseudo-Boolean optimization
      (QPBO) graph cut was incorporated into a multi-scale framework, where field map
      solutions are propagated from coarse to fine scales for voxels that are not
      resolved by the graph cut. The accuracy of the single-scale and multi-scale QPBO
      algorithms was evaluated against benchmark reference datasets. The robustness to
      noise was evaluated by adding noise to the input data prior to water-fat
      separation. RESULTS: Both algorithms achieved the highest accuracy when compared
      with seven previously published methods, while computation times were acceptable
      for implementation in clinical routine. The multi-scale algorithm was more robust
      to noise than the single-scale algorithm, while causing only a small increase
      (+10%) of the reconstruction time. CONCLUSION: The proposed 3D multi-scale QPBO
      algorithm offers accurate water-fat separation, robustness to noise, and fast
      reconstruction. The software implementation is freely available to the research
      community. Magn Reson Med 78:941-949, 2017. (c) 2016 International Society for
      Magnetic Resonance in Medicine.

PMID- 27714827
TI  - Immunomodulatory effects of metal salts at sub-toxic concentrations.
AB  - Because different metals are used in complementary medicine for the treatment of
      diseases related to a dysfunction of the immune system, this study aimed at
      determining the immunomodulatory potential of Pb(NO3 )2 , AuCl3 , Cu(NO3 )2 ,
      HgCl2 , AgNO3 , SnCl2 , AsCl3 and SbCl3 at sub-toxic concentrations and at
      assessing possible toxic side effects of low-concentrated metal preparations. The
      influence of the metal salts on primary human mononuclear cells was analyzed by
      measuring cell viability using the water-soluble tetrazolium salt assay,
      apoptosis and necrosis induction by annexin V/propidium iodide staining and
      proliferation by carboxyfluorescein diacetate succinimidyl ester staining and
      flow cytometry. Effects on T-cell activation were assessed with CD69 and CD25
      expression using flow cytometry whereas CD83, CD86 and CD14 expression was
      measured to evaluate the influence on dendritic cell maturation. Alterations of
      interleukin-2 and interferon-gamma secretion were detected by enzyme-linked
      immunosorbent assay and genotoxic effects were analyzed using the comet assay. At
      sub-toxic concentrations retardation of T-cell proliferation was caused by Pb(NO3
      )2 , AuCl3 and Cu(NO3 )2 and inhibitory effects on interleukin-2 secretion were
      measured after incubation with Pb(NO3 )2 , AuCl3 , Cu(NO3 )2 , HgCl2 and AsCl3.
      Cu(NO3 )2 had immunosuppressive activity at dosages within the serum reference
      range for copper. All other metal salts showed effects at dosages above upper
      serum limits of normal. Therefore, only low-concentrated copper preparations are
      promising to have immunomodulatory potential. Toxic side effects of metal
      preparations used in complementary medicine are improbable because upper limits
      of metals set in the drinking water ordinance are either not exceeded or the
      duration of their application is limited. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 27714828
TI  - A propeptide-independent protease from Tannerella sp.6_1_58FAA_CT1 displays
      trypsin-like specificity.
AB  - Despite the absence of any homologs of Tannerella forsythia KLIKK proteases in
      Tannerella sp.6_1_58FAA_CT1, the strain possesses a putative cysteine protease
      (G9S4N1) closely related to RgpB of Porphyromonas gingivalis. G9S4N1 lacks
      obvious propeptide that behaves as inhibitor of proteases and was proven to be a
      propeptide-independent protease. Unlike RgpB, which exclusively cleaves Arg?Xaa
      bonds, G9S4N1 exhibits both arginine- and citrulline-specific activities.
      Mutations of Asp177, a potential P1-Arg binding site, to uncharged or positively
      charged residues did not alter the substrate specificity of G9S4N1 significantly.
      Moreover, a group of arginine-specific proteases from different species including
      porcine trypsin, bovine thrombin, and a trypsin-like serine protease of dengue 2
      virus CF40-Gly-NS3pro185 also display different specificity toward citrulline
      residue, suggesting that citrulline-modified protein might have different roles
      and destiny in biological processes involving various proteases.

PMID- 27714829
TI  - Biological factor related to Asian sand dust particles contributes to the
      exacerbation of asthma.
AB  - Epidemiologic studies have revealed that Asian sand dust particles (ASDs) can
      affect respiratory and immune health represented by asthma. Factors responsible
      for the exacerbation of asthma remain unclear. The fungus Bjerkandera adusta
      (B.ad) and polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) have
      been identified in ASDs collected from the atmosphere when an ASD event occurred.
      We investigated the effects of B.ad and BaP related to ASDs on respiratory and
      immune systems. Bone marrow-derived antigen-presenting cells (APCs) and
      splenocytes from atopic prone NC/Nga mice and human airway epithelial cells were
      exposed to the B.ad or to BaP in the presence and absence of heated-ASDs (H
      ASDs). B.ad and BaP in both the presence and absence of H-ASDs increased the
      expression of cell surface molecules on APCs. H-ASDs alone slightly activated
      APCs. The expressions induced by B.ad were higher than those induced by BaP in
      the presence and absence of H-ASDs. There were no remarkable effects on the
      activation of splenocytes or the proinflammatory responses in airway epithelial
      cells. These results suggest that B.ad rather than BaP contributes to the
      exacerbation of asthma regardless of the presence or absence of sand particles,
      particularly by the activation of the immune system via APCs. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27714830
TI  - LC-MS/MS method development for quantification of doxorubicin and its metabolite
      13-hydroxy doxorubicin in mice biological matrices: Application to a pharmaco
      delivery study.
AB  - This study describes the development of simple, rapid and sensitive liquid
      chromatography tandem mass spectrometry method for the simultaneous analysis of
      doxorubicin and its major metabolite, doxorubicinol, in mouse plasma, urine and
      tissues. The calibration curves were linear over the range 5-250 ng/mL for
      doxorubicin and 1.25-25 ng/mL for doxorubicinol in plasma and tumor, over the
      range 25-500 ng/mL for doxorubicin and 1.25-25 ng/mL for doxorubicinol in liver
      and kidney, and over the range 25-1000 ng/mL for doxorubicin and doxorubicinol in
      urine. The study was validated, using quality control samples prepared in all
      different matrices, for accuracy, precision, linearity, selectivity, lower limit
      of quantification and recovery in accordance with the US Food & Drug
      Administration guidelines. The method was successfully applied in determining the
      pharmaco-distribution of doxorubicin and doxorubicinol after intravenously
      administration in tumor-bearing mice of drug, free or nano-formulated in ferritin
      nanoparticles or in liposomes. Obtained results demonstrate an effective
      different distribution and doxorubicin protection against metabolism linked to
      nano-formulation. This method, thanks to its validation in plasma and urine,
      could be a powerful tool for pharmaceutical research and therapeutic drug
      monitoring, which is a clinical approach currently used in the optimization of
      oncologic treatments.

PMID- 27714831
TI  - Vedolizumab provides clinical benefit over 1 year in patients with active
      inflammatory bowel disease - a prospective multicenter observational study.
AB  - BACKGROUND: Vedolizumab, a monoclonal antibody targeting the alpha4beta7
      integrin, is effective in inducing and maintaining clinical remission in Crohn's
      disease and ulcerative colitis according to randomised clinical trials. AIM: To
      determine the long-term effectiveness of vedolizumab in a real-world clinical
      setting. METHODS: This observational registry assessed the clinical outcome in
      patients treated with vedolizumab for clinically active Crohn's disease (n = 67)
      or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI <=
      4/pMayo <= 1) at week 54. Secondary endpoints included clinical response rates
      (HBI/pMayo score drop >=3) and steroid-free clinical remission at weeks 30 and
      54. RESULTS: Vedolizumab was stopped in 69/127 (56%) patients after a median time
      of 18 weeks (range 2-49) predominantly owing to lack or loss of response. Using
      nonresponder imputation analysis, clinical remission and steroid-free remission
      rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis,
      respectively. Lack of clinical remission was associated with prior treatment with
      anti-TNF or with steroids for more than 3 months in the last 6 months in
      ulcerative colitis. At week 14, the absence of remission in Crohn's disease or
      nonresponse in ulcerative colitis indicated a low likelihood of clinical
      remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative
      colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease
      and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted
      remission at week 54. CONCLUSION: Among patients who started vedolizumab for
      active inflammatory bowel disease, clinical remission rates are 21-25% after 54
      weeks.

PMID- 27714833
TI  - High-Dose Venous Thromboembolism Prophylaxis for Obese Patients.

PMID- 27714832
TI  - In vivo pH mapping of injured lungs using hyperpolarized [1-13 C]pyruvate.
AB  - PURPOSE: To optimize the production of hyperpolarized 13 C-bicarbonate from the
      decarboxylation of hyperpolarized [1-13 C]pyruvate and use it to image pH in the
      lungs and heart of rats with acute lung injury. METHODS: Two forms of catalysis
      are compared calorimetrically to maximize the rate of decarboxylation and rapidly
      produce hyperpolarized bicarbonate from pyruvate while minimizing signal loss.
      Rats are injured using an acute lung injury model combining ventilator-induced
      lung injury and acid aspiration. Carbon images are obtained from both healthy (n
      = 4) and injured (n = 4) rats using a slice-selective chemical shift imaging
      sequence with low flip angle. pH is calculated from the relative HCO3- and CO2
      signals using the Henderson-Hasselbalch equation. RESULTS: It is demonstrated
      that base catalysis is more effective than metal-ion catalysis for this
      decarboxylation reaction. Bicarbonate polarizations up to 17.2% are achieved
      using the base-catalyzed reaction. A mean pH difference between lung and heart of
      0.14 pH units is measured in the acute lung injury model. A significant pH
      difference between injured and uninjured lungs is also observed. CONCLUSION: It
      is demonstrated that hyperpolarized 13 C-bicarbonate can be efficiently produced
      from the base-catalyzed decarboxylation of pyruvate. This method is used to
      obtain the first regional pH image of the lungs and heart of an animal. Magn
      Reson Med 78:1121-1130, 2017. (c) 2016 International Society for Magnetic
      Resonance in Medicine.

PMID- 27714834
TI  - Low dose methotrexate induced asymptomatic keratinocyte dystrophy in a patient of
      psoriasis vulgaris.

PMID- 27714835
TI  - Comparison of the local pulmonary distribution of nanoparticles administered
      intratracheally to rats via gavage needle or microsprayer delivery devices.
AB  - Intratracheal administration methods are used to conduct toxicological
      assessments of inhaled nanoparticles (NPs), and gavage needles or microsprayers
      are common intratracheal delivery devices. The NP suspension is delivered in a
      liquid state via gavage needle and as a liquid aerosol via microsprayer. The
      differences in local pulmonary NP distribution (called the microdistribution)
      arising from the different states of the NP suspension cause differential
      pulmonary responses; however, this has yet to be investigated. Herein, using
      microbeam X-ray fluorescence microscopy, we quantitatively evaluated the TiO2
      pulmonary microdistribution (per mesh: 100 MUm * 100 MUm) in lung sections from
      rats administered an intratracheal dose of TiO2 NPs (6 mg kg-1 ) via gavage
      needle or microsprayer. The results revealed that: (i) using a microsprayer
      appears to reduce the variations in TiO2 content (ng mesh-1 ) among rats (e.g.,
      coefficients of variation, n = 3, microsprayer vs gavage needle: 13% vs 30%, for
      the entire lungs); (ii) TiO2 appears to be deposited less in the right middle
      lobes than in the rest of the lung lobes, irrespective of the chosen
      intratracheal delivery device; and (iii) similar TiO2 contents (ng mesh-1 ) and
      frequencies are deposited in the lung lobes of rats administered TiO2 NPs via
      gavage needle or microsprayer. This suggests that the physical state of the
      administered NP suspension does not markedly alter TiO2 pulmonary
      microdistribution. The results of this investigation are important for the
      standardization of intratracheal administration methods. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27714836
TI  - Ingestion of Bt rice pollen does not reduce the survival or hypopharyngeal gland
      development of Apis mellifera adults.
AB  - Because of its ecological and economic importance, the honey bee Apis mellifera
      is commonly used to assess the environmental risk of insect-resistant,
      genetically modified plants. In the present study, feeding-exposure experiments
      were used to determine whether pollen from transgenic rice harms A. mellifera
      worker bees. In 1 experiment, the survival and mean acinus diameter of
      hypopharyngeal glands of adult bees were similar when bees were fed on pollen
      from Bt rice lines or from a non-Bt rice line, but bee survival was significantly
      reduced when they received pollen that was mixed with potassium arsenate as a
      positive control. In a second experiment, bee survival and hypopharyngeal gland
      development were not reduced when adult bees were fed on non-Bt pollen and a
      sucrose solution supplemented with Cry2A at 400 ug/g, Cry1C at 50 ug/g, or bovine
      serum albumin (BSA) at 400 ug/g, but bee survival and hypopharyngeal gland
      development were reduced when the diet was supplemented with soybean trypsin
      inhibitor as a positive control. In both experiments, the uptake of Cry proteins
      by adult bees was confirmed. Overall, the results indicate that the planting of
      Bt rice lines expressing Cry2A or Cry1C protein poses a negligible risk to A.
      mellifera worker bees. Environ Toxicol Chem 2017;36:1243-1248. (c) 2016 SETAC.

PMID- 27714837
TI  - Extracellular ATP induces graded reactive response of astrocytes and strengthens
      their antioxidative defense in vitro.
AB  - It is widely accepted that adenosine triphosphate (ATP) acts as a universal
      danger-associated molecular pattern with several known mechanisms for immune cell
      activation. In the central nervous system, ATP activates microglia and astrocytes
      and induces a neuroinflammatory response. The aim of the present study was to
      describe responses of isolated astrocytes to increasing concentrations of ATP (5
      uM to 1 mM), which were intended to mimic graded intensity of the extracellular
      stimulus. The results show that ATP induces graded activation response of
      astrocytes in terms of the cell proliferation, stellation, shape remodeling, and
      underlying actin and GFAP filament rearrangement, although the changes occurred
      without an apparent increase in GFAP and actin protein expression. On the other
      hand, ATP in the range of applied concentrations did not evoke IL-1beta release
      from cultured astrocytes, nor did it modify the release from LPS and LPS+IFN
      gamma-primed astrocytes. ATP did not promote astrocyte migration in the wound
      healing assay, nor did it increase production of reactive oxygen and nitrogen
      species and lipid peroxidation. Instead, ATP strengthened the antioxidative
      defense of astrocytes by inducing Cu/ZnSOD and MnSOD activities and by increasing
      their glutathione content. Our current results suggest that although ATP triggers
      several attributes of activated astrocytic phenotype with a magnitude that
      increases with the concentration, it is not sufficient to induce full-blown
      reactive phenotype of astrocytes in vitro. (c) 2016 Wiley Periodicals, Inc.

PMID- 27714839
TI  - Potential for high-permittivity materials to reduce local SAR at a pacemaker lead
      tip during MRI of the head with a body transmit coil at 3 T.
AB  - PURPOSE: To illustrate the potential for high permittivity materials to be used
      in decreasing peak local SAR associated with implants when the imaging region is
      far from the implant. METHODS: We performed numerical simulations of a human
      subject with a pacemaker in a body-sized birdcage coil driven at 128 MHz with and
      without a thin (5 mm) shell of material of high electric permittivity around the
      head. RESULTS: For a shell with relative permittivity of 600, the maximum
      specific energy absorption rate averaged over any 1 g of tissue near the
      pacemaker was reduced by 73.5% for a given B1 field strength at the center of the
      brain. CONCLUSION: Although further study is required, initial simulations
      indicate that strategic use of high permittivity materials may broaden the
      conditions under which patients with certain implants can be imaged safely. Magn
      Reson Med 78:383-386, 2017. (c) 2016 International Society for Magnetic Resonance
      in Medicine.

PMID- 27714838
TI  - Pharmacologically Inactive Bisphosphonates as an Alternative Strategy for
      Targeting Osteoclasts: In Vivo Assessment of 5-Fluorodeoxyuridine-Alendronate in
      a Preclinical Model of Breast Cancer Bone Metastases.
AB  - Bisphosphonates have effects that are antiresorptive, antitumor, and
      antiapoptotic to osteoblasts and osteocytes, but an effective means of eliciting
      these multiple activities in the treatment of bone metastases has not been
      identified. Antimetabolite-bisphosphonate conjugates have potential for improved
      performance as a class of bone-specific antineoplastic drugs. The primary
      objective of the study was to determine whether an antimetabolite-bisphosphonate
      conjugate will preserve bone formation concomitant with antiresorptive and
      antitumor activity. 5-FdU-ale, a highly stable conjugate between the
      antimetabolite 5-fluoro-2'-deoxyuridine and the bisphosphonate alendronate, was
      tested for its therapeutic efficacy in a mouse model of MDA-MB231 breast cancer
      bone metastases. In vitro testing revealed osteoclasts to be highly sensitive to
      5-FdU-ale. In contrast, osteoblasts had significantly reduced sensitivity. Tumor
      cells were resistant in vitro but in vivo tumor burden was nevertheless
      significantly reduced compared with untreated mice. Sensitivity to 5-FdU-ale was
      not mediated through inhibition of farnesyl diphosphate synthase activity, but
      cell cycle arrest was observed. Although serum tartrate-resistant acid
      phosphatase (TRAP) levels were greatly reduced by both drugs, there was no
      significant decrease in the serum bone formation marker osteocalcin with 5-FdU
      ale treatment. In contrast, there was more than a fivefold decrease in serum
      osteocalcin levels with alendronate treatment (p < 0.001). This finding is
      supported by time-lapse micro-computed tomography analyses, which revealed bone
      formation volume to be on average 1.6-fold higher with 5-FdU-ale treatment
      compared with alendronate (p < 0.001). We conclude that 5-FdU-ale, which is a
      poor prenylation inhibitor but maintains potent antiresorptive activity, does not
      reduce bone formation and has cytostatic antitumor efficacy. These results
      document that conjugation of an antimetabolite with bisphosphonates offers
      flexibility in creating potent bone-targeting drugs with cytostatic, bone
      protection properties that show limited nephrotoxicity. This unique class of
      drugs may offer distinct advantages in the setting of targeted adjuvant therapy
      and chemoprevention of bone diseases. (c) 2016 American Society for Bone and
      Mineral Research.

PMID- 27714840
TI  - An analysis of free flap failure using the ACS NSQIP database. Does flap site and
      flap type matter?
AB  - PURPOSE: We sought to use the NSQIP database to determine the national rate and
      predictors of free flap failure based upon flap sites and flap types. METHODS:
      Free flaps were identified using the 2005-2010 NSQIP database. We examined
      overall flap failure rates as well as failure rates based upon flap sites (head
      and neck, extremities, trunk, and breast) and flap types (muscle, fascial, skin,
      bone, and bowel flaps). Univariate and multivariate analyses were used to
      determine predictors of flap failure. RESULTS: There were 1,187 microvascular
      free tissue transfers identified. The overall flap failure rate was 5.1%. Head
      and neck flaps had the highest rate of free flap failure at 7.7%. Prolonged
      operative time is an independent predictor of flap failure for all free flaps
      (OR: 2.383, P = 0.0013). When examining predictors of failure by flap site, free
      flaps to the breast with prolonged operative time are independently associated
      with flap failure (OR: 2.288, P = 0.0152). When examining predictors of flap
      failure by flap type, muscle based free flaps with an ASA classification >=3 are
      associated with flap failure (P = 0.0441). CONCLUSIONS: Risk factors for free
      flap failure differ based upon flap site and flap type. Prolonged operative time
      is an independent risk factor for the failure of free flaps used for breast
      reconstruction. An ASA classification >=3 is associated with the failure of free
      muscle based flaps. Our findings identify actionable areas that may help to
      improve free flap success.

PMID- 27714841
TI  - Random effects meta-analysis: Coverage performance of 95% confidence and
      prediction intervals following REML estimation.
AB  - A random effects meta-analysis combines the results of several independent
      studies to summarise the evidence about a particular measure of interest, such as
      a treatment effect. The approach allows for unexplained between-study
      heterogeneity in the true treatment effect by incorporating random study effects
      about the overall mean. The variance of the mean effect estimate is
      conventionally calculated by assuming that the between study variance is known;
      however, it has been demonstrated that this approach may be inappropriate,
      especially when there are few studies. Alternative methods that aim to account
      for this uncertainty, such as Hartung-Knapp, Sidik-Jonkman and Kenward-Roger,
      have been proposed and shown to improve upon the conventional approach in some
      situations. In this paper, we use a simulation study to examine the performance
      of several of these methods in terms of the coverage of the 95% confidence and
      prediction intervals derived from a random effects meta-analysis estimated using
      restricted maximum likelihood. We show that, in terms of the confidence
      intervals, the Hartung-Knapp correction performs well across a wide-range of
      scenarios and outperforms other methods when heterogeneity was large and/or study
      sizes were similar. However, the coverage of the Hartung-Knapp method is slightly
      too low when the heterogeneity is low (I2  < 30%) and the study sizes are quite
      varied. In terms of prediction intervals, the conventional approach is only valid
      when heterogeneity is large (I2  > 30%) and study sizes are similar. In other
      situations, especially when heterogeneity is small and the study sizes are quite
      varied, the coverage is far too low and could not be consistently improved by
      either increasing the number of studies, altering the degrees of freedom or using
      variance inflation methods. Therefore, researchers should be cautious in deriving
      95% prediction intervals following a frequentist random-effects meta-analysis
      until a more reliable solution is identified. (c) 2016 The Authors. Statistics in
      Medicine Published by John Wiley & Sons Ltd.

PMID- 27714842
TI  - High resolution MR imaging of pelvic lymph nodes at 7 Tesla.
AB  - PURPOSE: Pelvic lymph node (PLN) metastases are often smaller than 5 mm and
      difficult to detect. This work presents a method to perform PLN imaging with
      ultrahigh-field MRI, using spectrally selective excitation to acquire water and
      lipid-selective imaging at high spatial resolution. METHODS: A 3D water-selective
      multigradient echo (mGRE) sequence and lipid-selective gradient echo (GRE)
      sequence were tested in six healthy volunteers on a 7 Tesla (T) MRI system, using
      time interleaved acquisition of modes (TIAMO) to improve image homogeneity. The
      size distribution of the first 10 iliac PLNs detected in each volunteer was
      determined, and the contrast-to-noise ratio (CNR) of these lymph nodes (LNs) was
      compared with the individual mGRE images, sum-of-squares echo addition, and
      computed T2*-weighted images derived from the T2* fits. RESULTS: LN imaging was
      acquired robustly at ultrahigh field with high resolution and homogeneous lipid
      or water-selective contrast. PLNs down to 1.5-mm short axis were detected with
      mean +/- standard error of the mean (SEM) short and long axes of 2.2 +/- 0.1 and
      3.7 +/- 0.2 mm, respectively. Computed T2*-weighted imaging allowed flexibility
      in T2* contrast while featuring a CNR up to 90% of the sum-of-squares echo
      addition. CONCLUSION: Ultrahigh-field MRI in combination with TIAMO and frequency
      selective excitation enables high-resolution, large field-of-view MRI of the
      lower abdomen, and may ultimately be suitable for detecting small PLN metastases.
      Magn Reson Med 78:1020-1028, 2017. (c) 2016 International Society for Magnetic
      Resonance in Medicine.

PMID- 27714844
TI  - Evaluation and subsequent optimizations of the quantitative AmpliSens
      Florocenosis/Bacterial vaginosis-FRT multiplex real-time PCR assay for diagnosis
      of bacterial vaginosis.
AB  - Traditional microscopy-based methods for diagnosis of bacterial vaginosis (BV)
      are underutilized in many settings, and molecular techniques may provide
      opportunities for rapid, objective, and accurate BV diagnosis. This study
      evaluated the quantitative AmpliSens Florocenosis/Bacterial vaginosis-FRT
      multiplex real-time PCR (Florocenosis-BV) assay. Vaginal samples from a previous
      study including unselected female subjects (n = 163) and using Amsel criteria and
      454 pyrosequencing for BV diagnosis were examined with the Florocenosis-BV test
      and additionally tested for the presence and quantity of Gardnerella vaginalis
      clades 3 and 4. The Florocenosis-BV assay demonstrated 100% and 98% sensitivity
      compared with the Amsel criteria and 454 pyrosequencing, respectively, with 91%
      specificity. The modified Florocenosis-BV assay (detecting also G. vaginalis
      clades 3 and 4) resulted in 100% sensitivity vs the Amsel criteria and 454
      pyrosequencing with specificity of 86% and 88%, respectively. Further
      optimizations of thresholds for the quantitative parameters used in the kit
      resulted in 99-100% accuracy vs Amsel criteria and 454 pyrosequencing for
      selected parameters. The Florocenosis-BV assay is an objective, accurate,
      sensitive, and specific method for BV diagnosis; however, the performance of the
      test can be further improved with some minor optimizations.

PMID- 27714843
TI  - Acute tendon changes in intense CrossFit workout: an observational cohort study.
AB  - CrossFit is a fitness program that has become increasingly popular in the Western
      world, but as in other sports, the risk of injury is present. Only a few studies
      have addressed health benefits and injuries in CrossFit. It is known that
      chronically overloaded tendons will thicken and increase the risk of
      tendinopathy. However, it remains unknown whether acute overload caused by
      strenuous, high-intensity exercise will exert changes in tendons and if these
      changes can be detected and described by ultrasonography. The aim of this study
      is to evaluate the effects of acute overload on tendon thickness using
      ultrasonography. Standardized ultrasound measurements of the patella, Achilles,
      and plantaris tendons were performed before and after a specific workout in 34
      healthy subjects. Significant increases were observed in patella tendon thickness
      before (M = 4.5, SD = 0.6) and after (M = 5.0, SD = 0.7) highly intense strenuous
      exercise, with an estimated mean differences of 0.47 mm (95% CI: 0.35-0.59 mm; P
      < 0.0001) and in Achilles tendon thickness before (M = 4.4, SD = 0.4) and after
      (M = 4.5, SD = 0.5) workout, with an estimated difference of 0.17 mm (95% CI:
      0.04-0.29 mm; P < 0.01). However, there was no significant difference in fascia
      plantaris thickness before (M = 3.4, SD = 0.5) and after (M = 3.4, SD = 0.5)
      workout (P = 0.97). A significant increase in the thickness of the patellar and
      Achilles tendons was found in response to strenuous, highly intense CrossFit
      exercises. In order to understand the underlying mechanisms of the findings and
      possibly utilize this to gain a better understanding, further studies must be
      conducted.

PMID- 27714845
TI  - Contact allergens induce CD8+ T cell-derived interleukin 10 that appears
      dispensable for regulation of contact hypersensitivity.
AB  - Interleukin 10 (IL-10) has been implied in the regulation of allergic contact
      dermatitis. Using transcriptional reporter mice we analyzed cellular sources of
      IL-10 during contact hypersensitivity (CHS) and identified IL-10 expressing CD8+
      T cells in the skin that are antigen-specific, display PD-1, an effector memory
      phenotype, and IL-10 expression comparable to that of CD4+ T cells. However, in
      mice with a selective IL-10 deficiency in CD8+ T cells CHS responses were
      comparable to that of controls, even in the absence of CD4+ cells, suggesting
      that CD8+ T cell-derived IL-10 does not contribute significantly to the
      resolution of CHS responses.

PMID- 27714846
TI  - Both high expression of nucleophosmin/B23 and CRM1 predicts poorer prognosis in
      human gastric cancer.
AB  - Nucleophosmin/B23 and CRM1 are molecular markers which play an important role in
      tumorigenesis and tumor progression in gastric cancer (GC). However, the
      association between the two remains unclear. This study evaluated the expression
      and the correlation of B23 and CRM1 in GC. B23 and CRM1 expression in GC and
      adjacent noncancerous tissues (ANCT) of gastrectomy specimens from 131 GC
      patients was measured by immunohistochemistry. Positive expression rates of B23
      and CRM1 were significantly higher in GC tissues than in ANCT. The high
      expression rates of B23 and CRM1 were significantly higher in patients with more
      advanced tumor stages and distant metastasis (all p < 0.05). Only high expression
      of CRM1was correlated with positive Her2 status (p = 0.01). B23 expression was
      positively correlated with CRM1expression in GC tissues (p = 0.038). Univariate
      analysis showed that TNM stage (p = 0.0001), metastasis (p = 0.027), B23 (p =
      0.0111), and CRM1 expression (p = 0.0019) were significant risk factors affecting
      overall survival. Both high expression of B23 and CRM1 in GC patients suggests
      poor prognosis, co-expression of the two (p = 0.043) even worse. Cox multivariate
      analysis showed that positive B23 (p = 0.0231) and CRM1 (p = 0.0048) expression
      were both independent prognostic factors that negatively correlated with
      survival. We revealed the co-expression of B23 or CRM1 in GC. The expression
      levels of B23 or CRM1 were closely related to poor prognosis in GC, and both B23
      or CRM1 were independent risk factor.

PMID- 27714848
TI  - The regulatable MAL32 promoter in Saccharomyces cerevisiae: characteristics and
      tools to facilitate its use.
AB  - Here we describe a set of tools to facilitate the use of maltose and the MAL32
      promoter for regulated gene expression in yeast, alone or in combination with the
      GAL1 promoter. Using fluorescent protein reporters we find that under non
      inducing conditions the MAL32 promoter exhibits a low basal level of expression,
      similar to the GAL1 promoter, and that both promoters can be induced
      independently of each other using the respective sugars, maltose and galactose.
      While their repression upon glucose addition is immediate and complete, we found
      that the MAL32 and GAL1 promoters each exhibit distinct induction kinetics. A set
      of plasmids is available to facilitate the application of the MAL32 promoter for
      chromosomal modifications using PCR targetting and for plasmid based gene
      expression. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27714847
TI  - The Effects of Aging and Sex Steroid Deficiency on the Murine Skeleton Are
      Independent and Mechanistically Distinct.
AB  - Old age and sex steroid deficiency are the two most critical factors for the
      development of osteoporosis. It remains unknown, however, whether the molecular
      culprits of the two conditions are similar or distinct. We show herein that at
      19.5 months of age-a time by which the age-dependent decline of cortical and
      cancellous bone mass and cortical porosity were fully manifested in C57BL/6J mice
      these animals remained functionally estrogen sufficient. Transgenic mice with
      conditional expression of mitochondria-targeted catalase-a potent H2 O2
      inactivating enzyme-in cells of the myeloid lineage (mitoCAT;LysM-Cre mice) were
      protected from the loss of cortical, but not cancellous, bone caused by
      gonadectomy in either sex. Consistent with these findings, in vitro studies with
      ERalpha-deficient Prx1+ cells and gonadectomized young adult mice showed that in
      both sexes decreased ERalpha signaling in Prx1+ cells leads to an increase in
      SDF1, a.k.a. CXCL12, an osteoclastogenic cytokine whose effects were abrogated in
      macrophages from mitoCAT;LysM-Cre mice. In contrast to sex steroid deficiency,
      the adverse effects of aging on either cortical or cancellous bone were
      unaffected in mitoCAT;LysM-Cre mice. On the other hand, attenuation of H2 O2
      generation in cells of the mesenchymal lineage targeted by Prx1-Cre partially
      prevented the loss of cortical bone caused by old age. Our results suggest the
      effects of sex steroid deficiency and aging on the murine skeleton are
      independent and result from distinct mechanisms. In the former, the prevailing
      mechanism of the cortical bone loss in both sexes is increased osteoclastogenesis
      caused by estrogen deficiency; this is likely driven, at least in part, by
      mesenchymal/stromal cell-derived SDF1. Decreased osteoblastogenesis, owing in
      part to increased H2 O2, combined with increased osteoclastogenesis caused by
      aging mechanisms independent of estrogen deficiency, are the prevailing
      mechanisms of the loss of cortical bone with old age. (c) 2016 American Society
      for Bone and Mineral Research.

PMID- 27714850
TI  - Detection and comparison of neuraminidase activities in human and bovine group B
      streptococci.
AB  - Human and bovine group B streptococcus (GBS) isolates were serotyped and amounts
      of released N-acetylneuraminic acid from N-acetylneuraminyl-lactose by
      extracellular neuraminidase were colorimetrically assessed. According to
      serotyping by co-agglutination method, 30 of bovine GBS and 43 of human GBS could
      be serotyped (ST) by monospecific antisera coated with protein A. The remaining
      GBS strains were designated as nontypeable (NT). The released N-acetylneuraminic
      acid was determined in 90.9% of bovine GBS and 47.1% of human GBS isolates. The
      differences between the total bovine and human GBS isolates were statistically
      significant (p < 0.001). In comparison with detected N-acetylneuraminic acid
      level in bovine and human groups, significant decrease was observed in the bovine
      NT group according to increased human NT (p < 0.01) and bovine ST groups (p <
      0.01). However, N-acetylneuraminic acid level in bovine ST and bovine total
      groups significantly (p < 0.001) increased with respect to the human ST group and
      human total group. Neuraminidase activity was detected more frequently in bovine
      GBS isolates. Considerable differentiations were observed between typeable and
      nontypeable isolates.

PMID- 27714849
TI  - Psychosocial or clinico-demographic factors related to neuropsychiatric symptoms
      in patients with Alzheimer's disease needing interventional treatment: analysis
      of the CATIE-AD study.
AB  - OBJECTIVE: This study sought to determine psychosocial and clinico-demographic
      factors related to each symptomatic cluster (i.e., aggressiveness, psychosis,
      apathy/eating problems, and emotion/disinhibition) of neuropsychiatric symptoms
      (NPSs) in patients with Alzheimer's disease (AD) needing interventional treatment
      against their agitation or psychotic symptoms. These clusters were classified
      from 12 Neuropsychiatric Inventory (NPI) subscores in our previous study using
      the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's
      Disease (CATIE-AD) dataset. METHODS: Based on clinical data from 421 AD
      outpatients with agitation or psychotic symptoms needed interventional treatment
      enrolled in the CATIE-AD, we conducted logistic regression analyses to examine
      the relationships between each symptomatic cluster and three psychosocial
      (marital status, residence, and caregivers' burden) and nine clinico-demographic
      (age, gender, education year, general cognition, activity of daily living [ADL],
      general medical health, race, and intake of anti-dementia drugs or psychotropics)
      factors. RESULTS: While no factor contributed to aggressiveness, psychosis was
      associated with several clinico-demographic factors: female gender, non-Caucasian
      race, and lower cognitive function. Apathy/eating problems was associated with
      more severe caregiver burden, living in one's own home, lower ADL level, and male
      gender, while emotion/disinhibition was predicted by more severe caregiver
      burden, lower education level, not-married status, and younger age. CONCLUSIONS:
      Among the four NPS clusters, apathy/eating problems and emotion/disinhibition
      were associated with psychosocial as well as clinico-demographic factors in AD
      patients with psychotic symptoms or agitation needed interventional treatment.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27714851
TI  - Cynomolgus monkey model of interleukin-31-induced scratching depicts blockade of
      human interleukin-31 receptor A by a humanized monoclonal antibody.
AB  - Scratching is an important factor exacerbating skin lesions through the so-called
      itch-scratch cycle in atopic dermatitis (AD). In mice, interleukin (IL)-31 and
      its receptor IL-31 receptor A (IL-31RA) are known to play a critical role in
      pruritus and the pathogenesis of AD; however, study of their precise roles in
      primates is hindered by the low sequence homologies between primates and mice and
      the lack of direct evidence of itch sensation by IL-31 in primates. We showed
      that administration of cynomolgus IL-31 induces transient scratching behaviour in
      cynomolgus monkeys and by that were able to establish a monkey model of
      scratching. We then showed that a single subcutaneous injection of 1 mg/kg
      nemolizumab, a humanized anti-human IL-31RA monoclonal antibody that also
      neutralizes cynomolgus IL-31 signalling and shows a good pharmacokinetic profile
      in cynomolgus monkeys, suppressed the IL-31-induced scratching for about 2
      months. These results suggest that the IL-31 axis and IL-31RA axis play as
      critical a role in the induction of scratching in primates as in mice and that
      the blockade of IL-31 signalling by an anti-human IL-31RA antibody is a promising
      therapeutic approach for treatment of AD. Nemolizumab is currently under
      investigation in clinical trials.

PMID- 27714852
TI  - Physical fitness and academic performance in youth: A systematic review.
AB  - Physical fitness (PF) is a construct of health- and skill-related attributes
      which have been associated with academic performance (AP) in youth. This study
      aimed to review the scientific evidence on the association among components of PF
      and AP in children and adolescents. A systematic review of articles using
      databases PubMed/Medline, ERIC, LILACS, SciELO, and Web of Science was
      undertaken. Cross-sectional and longitudinal studies examining the association
      between at least one component of PF and AP in children and adolescents,
      published between 1990 and June 2016, were included. Independent extraction of
      articles was carried out by the two authors using predefined data fields. From a
      total of 45 studies included, 25 report a positive association between components
      of PF with AP and 20 describe a single association between cardiorespiratory
      fitness (CRF) and AP. According to the Strengthening the Reporting of
      Observational Studies in Epidemiology guidelines: 12 were classified as low, 32
      as medium risk, and 1 as high risk of bias. Thirty-one studies reported a
      positive association between AP and CRF, six studies with muscular strength,
      three studies with flexibility, and seven studies reported a positive association
      between clustered of PF components and AP. The magnitude of the associations is
      weak to moderate (beta = 0.10-0.42 and odds = 1.01-4.14). There is strong
      evidence for a positive association between CRF and cluster of PF with AP in
      cross-sectional studies; and evidence from longitudinal studies for a positive
      association between cluster of PF and AP; the relationship between muscular
      strength and flexibility with AP remains uncertain.

PMID- 27714854
TI  - Molecular diagnostics of inflammatory disease: New tools and perspectives.
AB  - This essay reviews current approaches to establish novel molecular diagnostic
      tools for inflammatory skin diseases. Moreover, it highlights the importance of
      stratifying patients according to molecular signatures and revising current
      outdated disease classification systems to eventually reach the goal of
      personalized medicine.

PMID- 27714853
TI  - Liver transplant recipients with portal vein thrombosis receiving an organ from a
      high-risk donor are at an increased risk for graft loss due to hepatic artery
      thrombosis.
AB  - We hypothesize that recipients with pretransplant portal vein thrombosis (PVT)
      receiving organs from high-risk donors (HRD) are at an increased risk of HAT.
      Data on all liver transplants in the United States from February 2002 to March
      2015 were analyzed. Recipients were sorted into two groups: those with PVT and
      those without. HRDs were defined by donor risk index (DRI) >1.7. Multivariable
      logistic regression models were constructed to assess the independent risk
      factors for HAT with the resultant graft loss <=90 days from transplantation. A
      total of 60 404 candidates underwent liver transplantation; of those recipients,
      623 (1.0%) had HAT, of which 66.0% (n = 411) received organs from HRDs compared
      with 49.3% (n = 29 473) in recipients without HAT (P < 0.001); 2250 (3.7%)
      recipients had pretransplantation PVT and received organs from HRDs. On adjusted
      multivariable analysis, PVT with a HRD organ was the most significant independent
      risk factor (OR 3.56, 95% CI 2.52-5.02, P < 0.001) for the development of HAT.
      Candidates with pretransplant PVT who receive an organ from a HRD are at the
      highest risk for postoperative HAT independent of other measurable factors.
      Recipients with pretransplant PVT would benefit from careful donor selection and
      possibly anticoagulation perioperatively.

PMID- 27714855
TI  - Role of carbohydrate in central fatigue: a systematic review.
AB  - Carbohydrate (CHO) depletion is linked to neuromuscular fatigue during exercise.
      While its role at peripheral level is relatively well understood, less is known
      about its impact centrally. The aim of this systematic review was to critically
      analyze the effects of CHO on central fatigue (CF) assessed by various
      neurophysiological techniques. Four databases were searched using PRISMA
      guidelines through February 2016. The inclusion criteria were: CHO as
      intervention against a placebo control, fatigue induced by prolonged exercise and
      assessed using neurophysiological measures [voluntary activation (VA),
      superimposed twitch (SIT), M-wave, electromyography], alongside maximal voluntary
      contraction (MVC). Seven papers were reviewed, where exercise duration lasted
      between 115 and 180 min. CHO improved exercise performance in three studies,
      whereby two of them attributed it to CF via attenuation of VA and SIT reductions,
      while the other indicated peripheral involvement via attenuation of M-wave
      reduction. Although a few studies suggest that CHO attenuates CF, data on its
      direct effects on neurophysiological outcome measures are limited and mixed.
      Generally, measures employed in these studies were inadequate to conclude central
      contribution to fatigue. Factors including the techniques used and the lack of
      controls render additional confounding factors to make definitive deductions.
      Future studies should employ consistent techniques and appropriate
      neurophysiological controls to distinguish CHO effect at central level. The use
      of pharmacological intervention should be incorporated to elucidate involvement
      of central mechanisms.

PMID- 27714856
TI  - High diversity of the T-cell receptor repertoire of tumor-infiltrating
      lymphocytes in basal cell carcinoma.
AB  - Whether specific T-cell clones are present in tumor infiltrating lymphocytes
      (TILs) in BCC is unknown. We employed deep sequencing of mRNA coding for the T
      cell receptor (TCR) chains alpha- and beta to characterize the repertoire of TILs
      in BCC. V and J gene-usage and CDR3 length were computed to determine the
      clonality of TCR and degree of overlap in TCR repertoires between skin resident T
      cells and TILs. We found high diversity of the TCR repertoire in BCC and control
      skin with random V-J gene usage and similar CDR3-length distribution. Lack of TCR
      repertoire restriction indicates absence of tumor-specific TIL clones in BCC.

PMID- 27714857
TI  - Depigmentation of alpha-melanocyte-stimulating hormone-treated melanoma cells by
      beta-mangostin is mediated by selective autophagy.
AB  - Melanogenesis is a key pathway for the regulation of skin pigmentation and the
      development of skin-lightening/skin-whitening drugs or cosmetics. In this study,
      we found that beta-mangostin from seedcases of Garcinia mangostana inhibited
      alpha-melanocyte-stimulating hormone (alpha-MSH)-mediated melanogenesis in B16F10
      melanoma cells and a three-dimensional human skin model. beta-Mangostin
      significantly inhibited the protein level of tyrosinase induced by alpha-MSH in
      UPS (ubiquitin proteasome system)-independent and lysosome-dependent manner. The
      inhibition of autophagy by 3-methyladenine treatment or ATG5 knockdown
      effectively recovered premelanosome protein as well as tyrosinase degraded by the
      beta-mangostin treatment. However, rapamycin, a representative non-selective
      autophagy inducer, triggered autophagy in alpha-MSH-stimulated cells, which was
      characterized by a considerable decrease in p62, but it was unable to inhibit
      melanogenesis. Melanosome-engulfing autophagosomes were observed using
      transmission electron microscopy. Furthermore, previously formed melanin could be
      degraded effectively in an autophagy-dependent manner in beta-mangostin-treated
      cells. Taken together, our results suggest that beta-mangostin inhibits the
      melanogenesis induced by alpha-MSH via an autophagy-dependent mechanism, and
      thus, the depigmentation effect of beta-mangostin may depend on autophagy
      targeted at the melanosome rather than non-selective autophagy.

PMID- 27714858
TI  - Long-term consequences of vocal fold hemorrhage.
AB  - OBJECTIVES/HYPOTHESIS: To assess the long-term impact of vocal fold hemorrhage
      (VFH) on vocal function and health, and compare these parameters to those in
      similar patients who have not had VFH. STUDY DESIGN: Retrospective cohort study.
      METHODS: Patients with a history of VFH (N = 41) were characterized through a
      review of records and assessed by means of a survey for vocal health and
      professional functioning as well as the Voice Handicap Index-10 (VHI-10) and, if
      appropriate (n = 30, 73.2%), the Singing Voice Handicap Index (SVHI-10). They
      were compared to a group of demographically and occupationally similar patients
      without VFH (N = 25, 60.9%). Patients with multiple episodes of VFH (n = 9,
      22.0%) were compared to patients with a single event. RESULTS: After a median of
      41 months follow-up, patients with VFH had favorable vocal function assessment
      and low median VHI-10 and SVHI-10 scores (4 and 6, respectively), substantially
      similar to patients without VFH (VHI-10, P = .905 and SVHI 10, P =.991). The two
      groups showed similarly low rates of change in occupation (7.3%vs. 8.0%, P
      =.999). Patients with VFH were more likely to have missed days of work due to a
      voice problem. Analysis of patients with one versus multiple VFH episodes showed
      no differences, except patients with multiple episodes had significantly greater
      confidence in their ability to address future VFH. CONCLUSIONS: Contrary to
      commonly held belief, VFH appears to have no significant long-term impact on
      vocational stability, subjective voice quality, or perceptions of vocal function.
      Moreover, among those with VFH, recurrence seems only to diminish anxiety over
      this transient injury. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:900-906, 2017.

PMID- 27714859
TI  - Evaluation of Basal Serum or Plasma Cortisol Concentrations for the Diagnosis of
      Hypoadrenocorticism in Dogs.
AB  - BACKGROUND: Previous studies that included limited numbers of affected dogs have
      suggested basal cortisol concentrations <=55 nmol/L (2 MUg/dL) are sensitive, but
      nonspecific, for a diagnosis of hypoadrenocorticism. A detailed assessment of the
      diagnostic utility of basal cortisol concentrations is warranted.
      HYPOTHESIS/OBJECTIVES: To evaluate the utility of basal cortisol concentrations
      for the diagnosis of hypoadrenocorticism in a large number of dogs, including
      those with and without serum electrolyte abnormalities. ANIMALS: Five hundred and
      twenty-two dogs, including 163 dogs with hypoadrenocorticism, 351 dogs with
      nonadrenal gland illness, and 8 dogs with equivocal results. METHODS:
      Retrospective study. Basal and post-ACTH cortisol concentrations and sodium and
      potassium concentrations were collected from medical records. A receiver
      operating characteristic (ROC) curve was constructed for basal cortisol
      concentrations by standard methodologies. Sensitivity, specificity, and
      predictive values were determined for various cut-points. RESULTS: The area under
      the ROC curve was 0.988 and was similarly excellent regardless of serum
      electrolyte concentrations. At the most discriminatory cut-point of 22 nmol/L
      (0.8 MUg/dL), sensitivity and specificity were 96.9 and 95.7%, respectively. A
      basal cortisol concentration of <=55 nmol/L (2 MUg/dL) resulted in a sensitivity
      of 99.4%. Conversely, a basal cortisol concentration of <=5.5 nmol/L (0.19
      MUg/dL) resulted in a specificity of 99.1%. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Similar to findings in previous studies, basal cortisol concentrations >55 nmol/L
      (2 MUg/dL) are useful in excluding a diagnosis of hypoadrenocorticism.
      Interestingly, excellent specificities and positive predictive values were
      observed at lower cut-point cortisol concentrations.

PMID- 27714860
TI  - Quantitative and qualitative analysis of breakfast nutritional composition in
      French schoolchildren aged 9-11 years.
AB  - BACKGROUND: The present study aimed to analyse the nutritional quality of
      childrens' breakfasts using data collected during a cross-sectional observational
      study on the prevalence of urinary osmolality in 529 French children aged 9-11
      years. METHODS: Total nutrient intake, mean adequacy ratio (MAR), energy density
      and solid energy density were calculated from breakfast food and fluid
      nutritional composition. To identify the main qualitative breakfast patterns,
      each breakfast item was categorised into 15 solid and liquid food categories and
      a principal component analysis followed by a cluster analysis was performed.
      RESULTS: Only 9.8% included skipped breakfast. Breakfast provided, on average,
      22.9% of the recommended daily energy intake and 24.7% of the mean adequacy ratio
      of 23 key nutrients. Four breakfast patterns were identified: 'Sweets breakfast'
      (40.0% of children), 'Traditional French breakfast' (27.2%), 'Ready-to-eat cereal
      (RTEC) + milk' (18.1%) and 'Dairy and juice breakfast' (9.5%). Nutritionally, the
      'RTEC + milk' pattern was the most advantageous. Flavoured milk was the most
      frequently consumed food (50.5%) and the major component of the 'Traditional
      French breakfast'. CONCLUSIONS: Although breakfast provided a substantial
      contribution to a range of nutrients, opportunity for improvement, particularly
      to less nutrient breakfast patterns, should not be overlooked.

PMID- 27714861
TI  - Mechanically Reinforced Skin-Electronics with Networked Nanocomposite Elastomer.
AB  - Mechanically reinforced skin-electronics are presented by exploiting networked
      nanocomposite elastomers where high quality metal nanowires serve as conducting
      paths. Theoretical and experimental studies show that the established skin
      electronics exhibit superior mechanical enhancements against crack and
      delamination phenomena. Device applications include a class of biomedical devices
      that offers the ability of thermotherapeutic stimulation and electrophysiological
      monitoring, all via the skin.

PMID- 27714862
TI  - T-cell "induced-self" MHC class I/peptide complexes may enable "de novo"
      tolerance induction to neo-antigens occurring outside of the thymus: Lessons from
      the hair follicle.
AB  - The hair follicle (HF) epithelium can present self-antigens to cognate CD8+ T
      cells. These cells express periodically during the hair cycle arising or age
      related immunogenic proteins including HF-specific neo-antigens. We propose that
      IFN-gamma derived from the respective antigen-specific T cells spotting the
      particular self-peptides may thereby significantly induce and alter self-antigen
      presentation ("induced-self"). This induction, at first, may silence T cells,
      including neo-epitope-specific T cells. As the thymus cannot significantly
      recapitulate neo-epitopes evolving in the periphery, we propose that peripheral
      tissue-specific induction of MHC molecules presenting exactly these neo-epitopes
      by self-MHC/peptide-reactive CD8+ T cells is a key element of self-tolerance.
      Subsequently, however, the local perpetuation and modification of the same
      crosstalk in the context of HF immune privilege collapse can invite HF
      immunopathology, as typically seen in alopecia areata. This concept may
      essentially complement thymus-based regulation models of self/non-self
      discrimination beyond "missing-self" to the fine-tuned "induced-self" to ensure
      peripheral needs to maintain self-tolerance in the case of "danger" and any
      "alteration of self".

PMID- 27714864
TI  - Visioning the future for practice education.

PMID- 27714863
TI  - AP736 induces miR-125b expression for the efficient whitening and anti-ageing
      action in human epidermal cells.

PMID- 27714865
TI  - Recapping CAPs: The past 13 years of Critically Appraised Papers.

PMID- 27714867
TI  - USDA Fresh Fruit and Vegetable Program Is More Effective in Town and Rural
      Schools Than Those in More Populated Communities.
AB  - BACKGROUND: We attempted to determine effects of the United States Department of
      Agriculture (USDA) Fresh Fruit and Vegetable Program (FFVP) on variety and
      frequency of fruit and vegetable intake by students in schools from different
      locales. METHODS: Data were derived from the 2011-2012 Indiana FFVP Student
      Survey completed by 4229 fourth-sixth graders. Effects were studied within 2
      groups, 39 city and suburb schools, and 12 town and rural schools. Differences in
      students' responses over time to 2 items measuring variety and 10 items measuring
      fruit and vegetable intake frequency were determined with multilevel regression
      models. RESULTS: Town and rural students were 1.2 times more likely to eat
      different kinds of fruit (p = .04) and vegetables (p = .01) daily, and increased
      fruit (+1.0 time/day; p < .01) and vegetable intake frequency (+0.5 times/day; p
      = .03). City and suburb students increased fruit intake frequency (~0.8
      times/day; p < .01) but not vegetable intake frequency or daily variety (p >
      .05). CONCLUSIONS: FFVP improved fruit and vegetable eating behaviors in the
      "town and rural" group, but was only partially effective in the "city and suburb"
      group. Strategies to implement FFVP may need to differ depending on school
      locale.

PMID- 27714869
TI  - Impact of an Education Intervention on Missouri K-12 School Disaster and
      Biological Event Preparedness.
AB  - BACKGROUND: A 2011 nationwide school pandemic preparedness study found schools to
      be deficient. We examined the impact of a school nurse educational intervention
      aimed at improving K-12 school biological event preparedness. METHODS: Missouri
      Association of School Nurses (MASN) members were e-mailed a survey link in fall
      2013 (ie, preintervention), links to online education modules (ie, intervention)
      in late fall, and a postintervention survey link in spring, 2014. School
      biological event readiness was measured using 35 indicators, for a possible score
      range of 0-35. A paired t-test compared pre- to postintervention preparedness
      scores. RESULTS: A total of 133 school nurses (33.6% response rate) completed a
      survey; 35.3% of those (N = 47) completed both pre- and postintervention survey
      that could be matched. Pre- and postintervention preparedness scores ranged from
      5 to 28.5 (x? = 13.3) and 6.5 to 25 (x? = 14.8), respectively. Postintervention
      scores were significantly higher than preintervention scores for those who
      watched at least 1 module (t = -2.3, p < .05). CONCLUSION: The education
      intervention was effective at improving school preparedness, though the impact
      was small. The education intervention needs to be reassessed, especially in
      regard to providing a longer intervention period.

PMID- 27714868
TI  - Predictors of Obesity in a US Sample of High School Adolescents With and Without
      Disabilities.
AB  - BACKGROUND: Childhood obesity is a major public health concern. Children with
      disabilities have a higher prevalence of obesity. OBJECTIVE: We examined factors
      associated with obesity within a cross-sectional study of US adolescents with and
      without disabilities. METHODS: Data were obtained from the 2011 Youth Risk
      Behavior Survey. Logistic regression models were fitted to assess effects of
      dietary habits, physical activity, and unhealthy weight control behaviors on
      obesity. Effect modification by disability status was examined. RESULTS: Twenty
      percent (1986 of 9775 participants) reported a disability. Adolescents with
      disabilities were more likely to be obese (odds ratio [OR] = 1.7; 95% confidence
      interval [CI]: 1.3-2.1) and have at least 1 unhealthy weight control behavior (OR
      = 2.0; 95% CI: 1.6-2.5), and were less likely to be physically active (OR = 0.5;
      95% CI: 0.4-0.6). Lack of physical activity, increased television watching/video
      game playing, and unhealthy weight loss behaviors were significantly associated
      with obesity regardless of disability status (p-for-interaction >.05).
      CONCLUSIONS: Successful obesity interventions should target diet, physical
      activity, and weight control among adolescents with disabilities. Understanding
      barriers to healthier diet and physical activity for this population is critical
      to developing effective obesity prevention programs and reducing the prevalence
      of unhealthy weight control behaviors.

PMID- 27714870
TI  - Verbal Bullying Changes Among Students Following an Educational Intervention
      Using the Integrated Model for Behavior Change.
AB  - BACKGROUND: Bullying behavior in schools can lead to psychosocial problems.
      School-based interventions are important in raising student awareness, developing
      their skills and in planning to reduce bullying behavior. METHODS: A randomized
      controlled trial, using a school-based educational intervention to reduce verbal
      bullying, was conducted among grade 10 students in 16 urban and rural schools in
      KwaZulu-Natal, South Africa in 2013. Baseline and postintervention
      questionnaires, developed using the Integrated Model for Behavior Change
      theoretical model, were used to assess changes in verbal bullying. RESULTS:
      Postintervention there were reduced verbal bullying experiences. Improved social
      norms and awareness of verbal bullying were associated with reduced verbal
      bullying experiences and behavior. Although less likely to bully others verbally,
      girls were more likely to experience verbal bullying. Students with no living
      father were more likely to bully others verbally. CONCLUSIONS: The study findings
      indicate that a school-based intervention can positively impact on verbal
      bullying experiences and behavior.

PMID- 27714871
TI  - Explaining Disparities in Youth Aerobic Fitness and Body Mass Index: Relative
      Impact of Socioeconomic and Minority Status.
AB  - BACKGROUND: To advance research on youth fitness promotion it is important to
      understand factors that may explain the disparities in fitness. METHODS: We
      evaluated data from the FitnessGram NFL PLAY60 Partnership Project to examine
      school factors influencing aerobic capacity (AC) and body mass index (BMI) in
      schoolchildren. Individual observations for AC (157,971 students from 675
      schools) and BMI (178,274 students from 630 schools) were aggregated to compute
      the percentage of students achieving the Healthy Fitness Zone (HFZ). We examined
      achievements using adjusted linear regression models with socioeconomic status
      (SES), minority status, region, enrollment, and grade as factors. RESULTS: The
      mean HFZ for AC and BMI were 51.6% and 56.9%, respectively. SES, minority status,
      and enrollment were all significantly associated with AC HFZ among boys, and SES
      and enrollment were significant predictors of AC HFZ in girls. SES and location
      were significantly related to BMI HFZ among boys but only SES significantly
      predicted BMI HFZ in girls. Schools with higher SES had higher AC and BMI HFZ
      achievements. CONCLUSIONS: SES was consistently associated with health-related
      fitness, independent of sex, but not minority status.

PMID- 27714873
TI  - Food Literacy at Secondary Schools in Australia.
AB  - BACKGROUND: Food literacy can encourage adolescents to develop healthy dietary
      patterns. This study examined home economics teachers' (HET) perspectives of the
      importance, curriculum, self-efficacy, and food environments regarding food
      literacy in secondary schools in Australia. METHODS: A 20-item cross-sectional
      survey was completed by 205 HETs. The survey focused on the importance of aspects
      of food literacy, HETs' self-efficacy, and attitudes toward food literacy and
      schools' food environments. Data were analyzed descriptively, and associations
      between participants' demographic characteristics and perceptions were
      investigated by chi-square analyses. RESULTS: HETs rated aspects of food literacy
      including preparing and cooking food, knowing about healthy foods and food safety
      and hygiene practices as very important. They indicated animal welfare, where
      food comes from, and plan and manage time for food shopping to be the least
      important aspects of food literacy. HETs reported that students' involvement in
      food literacy activities resulted in healthier diets and improved food practices,
      but the schools' food environments are not comprehensively supportive of food
      literacy. CONCLUSIONS: HETs report that food literacy is very important for
      adolescents to learn. The focus is more on microaspects in comparison to
      macroaspects of food literacy. Schools' food environments are ideally positioned
      to shape dietary intake of adolescents but their potential is not being realized.

PMID- 27714872
TI  - Socioeconomic Factors Influence Physical Activity and Sport in Quebec Schools.
AB  - BACKGROUND: School environments providing a wide selection of physical activities
      and sufficient facilities are both essential and formative to ensure young people
      adopt active lifestyles. We describe the association between school opportunities
      for physical activity and socioeconomic factors measured by low-income cutoff
      index, school size (number of students), and neighborhood population density.
      METHODS: A cross-sectional survey using a 2-stage stratified sampling method
      built a representative sample of 143 French-speaking public schools in Quebec,
      Canada. Self-administered questionnaires collected data describing the physical
      activities offered and schools' sports facilities. Descriptive and bivariate
      analyses were performed separately for primary and secondary schools. RESULTS: In
      primary schools, school size was positively associated with more intramural and
      extracurricular activities, more diverse interior facilities, and activities
      promoting active transportation. Low-income primary schools were more likely to
      offer a single gym. Low-income secondary schools offered lower diversity of
      intramural activities and fewer exterior sporting facilities. High-income
      secondary schools with a large school size provided a greater number of
      opportunities, larger infrastructures, and a wider selection of physical
      activities than smaller low-income schools. CONCLUSIONS: Results reveal an
      overall positive association between school availability of physical and sport
      activity and socioeconomic factors.

PMID- 27714874
TI  - The Role of Ethnicity in School-Based Obesity Intervention for School-Aged
      Children: A Pilot Evaluation.
AB  - BACKGROUND: Rates of obesity have risen disproportionately for ethnic minority
      youth in the United States. School-based programs may be the most comprehensive
      and cost-effective way to implement primary prevention in children. In this study
      we evaluated the effect of a school-based obesity prevention on the outcome of
      body mass index percentile (BMI%), with baseline weight class and ethnicity
      examined as moderators. METHODS: Participants (N = 125), ages 7-11 (56% female)
      from 4 urban, low-income, ethnic minority (58% black, 42% Latino) schools were
      recruited. Two schools received the Urban Initiatives Work to Play health
      intervention, and 2 demographically matched schools served as wait-list controls.
      RESULTS: Hierarchical multiple regression was used to analyze the independent and
      interactive effects of key variables on BMI%. An interaction between intervention
      status and ethnicity revealed Latino youth in the intervention had lower BMI%
      than those in the control group. Participation did not cause BMI% outcomes to
      decrease for black participants. CONCLUSIONS: The study demonstrates the
      intervention is effective, but that the effectiveness varies across ethnicity.
      Interventions can be made more efficient and cost-effective by targeting youth of
      a common ethnicity that has shown empirical responsiveness to certain program
      elements.

PMID- 27714875
TI  - Victims of Bullying and Tobacco Use Behaviors in Adolescents: Differences Between
      Bullied at School, Electronically, or Both.
AB  - BACKGROUND: Being a victim of bullying is associated with greater risk of youth
      substance use; however, research specifically examining whether tobacco use
      behaviors differ among adolescents who were bullied at school only,
      electronically only, or both at school and electronically is limited. METHODS: We
      examined the associations between being a victim of bullying (at school only,
      electronically only, or both at school and electronically) and use of tobacco
      products using data from the 2013 national Youth Risk Behavior Survey. RESULTS:
      Girls who were bullied both at school and electronically reported the highest
      odds of all tobacco use behaviors (ever use of cigarettes, current use of
      cigarettes, and current use of any tobacco product) as compared with girls who
      were not bullied after adjusting for covariates. Conversely, for boys, only the
      association between being bullied electronically only and ever use of cigarettes
      remained significant after adjusting for covariates. CONCLUSIONS: Results from
      this study indicate that electronic bullying may differentially influence the
      odds of tobacco use in high school students as compared with bullying that occurs
      at school only. Confirmation of these findings could inform interventions to
      reduce both bullying and tobacco use in high school.

PMID- 27714876
TI  - Two-Dimensional Cobalt-/Nickel-Based Oxide Nanosheets for High-Performance Sodium
      and Lithium Storage.
AB  - Two-dimensional (2D) nanomaterials are one of the most promising types of
      candidates for energy-storage applications due to confined thicknesses and high
      surface areas, which would play an essential role in enhanced reaction kinetics.
      Herein, a universal process that can be extended for scale up is developed to
      synthesise ultrathin cobalt-/nickel-based hydroxides and oxides. The sodium and
      lithium storage capabilities of Co3 O4 nanosheets are evaluated in detail. For
      sodium storage, the Co3 O4 nanosheets exhibit excellent rate capability (e.g.,
      179 mA h g-1 at 7.0 A g-1 and 150 mA h g-1 at 10.0 A g-1 ) and promising cycling
      performance (404 mA h g-1 after 100 cycles at 0.1 A g-1 ). Meanwhile, very
      impressive lithium storage performance is also achieved, which is maintained at
      1029 mA h g-1 after 100 cycles at 0.2 A g-1 . NiO and NiCo2 O4 nanosheets are
      also successfully prepared through the same synthetic approach, and both deliver
      very encouraging lithium storage performances. In addition to rechargeable
      batteries, 2D cobalt-/nickel-based hydroxides and oxides are also anticipated to
      have great potential applications in supercapacitors, electrocatalysis and other
      energy-storage-/-conversion-related fields.

PMID- 27714877
TI  - Reversal of warfarin anticoagulation using prothrombin complex concentrate at 25
      IU kg-1 : results of the RAPID study.
AB  - BACKGROUND: Real-world studies of the emergency reversal of warfarin using 4
      factor prothrombin complex concentrate (PCC) report unwarranted delays. The delay
      to receiving PCC was >= 8 h in 46.7% of patients with warfarin-associated
      bleeding (PWAB) treated with a variable PCC dosing protocol in our retrospective
      audit. OBJECTIVE: To report the impact of a simplified PCC dosing protocol on the
      interval to reversal of anticoagulation. METHODS: We developed a PCC dosing
      protocol standardising the initial PCC dose and simplifying dosing calculations.
      Study end points were the proportion of PWAB achieving international normalised
      ratio (INR) <=1.5 and treated within 8 h of presentation, respectively. RESULTS:
      Of 17, 15 (88.2%) PWABs achieved a post-treatment INR <= 1.5; 14 of 17 (82.4%)
      PWABs were reversed within 8 h. Median intervals between triage and PCC request
      and PCC request and start of infusion (administration interval) were 126 min
      (range 39-520) and 30 min (range 5-100), respectively. Compared with the
      retrospective cohort, RAPID is associated with an improved administration
      interval (mean 37.7 vs 76 min, P = 0.031) and the proportion of PWABs treated
      within 30 min (58.8 vs 6.7%, P = 0.009). CONCLUSION: The RAPID protocol reduces
      unwarranted delays without compromising efficacy.

PMID- 27714878
TI  - Bifunctional Platinated Nanoparticles for Photoinduced Tumor Ablation.
AB  - Bifunctional self-assembled nanoparticles with a platinated fluorophore core with
      ultra-low radiative transition are developed, which can generate both singlet
      oxygen and the photothermal effect for synergistic photodynamic and photothermal
      therapy with tumor ablation.

PMID- 27714879
TI  - Novel algorithm for management of acute epididymitis.
AB  - OBJECTIVES: To identify predictive factors for the severity of epididymitis and
      to develop an algorithm guiding decisions on how to manage patients with this
      disease. METHODS: A retrospective study was carried out on 160 epididymitis
      patients at Keio University Hospital. We classified cases into severe and non
      severe groups, and compared clinical findings at the first visit. Based on
      statistical analyses, we developed an algorithm for predicting severe cases. We
      validated the algorithm by applying it to an external cohort of 96 patients at
      Tokyo Medical Center. The efficacy of the algorithm was investigated by a
      decision curve analysis. RESULTS: A total of 19 patients (11.9%) had severe
      epididymitis. Patient characteristics including older age, previous history of
      diabetes mellitus and fever, as well as laboratory data including a higher white
      blood cell count, C-reactive protein level and blood urea nitrogen level were
      independently associated with severity. A predictive algorithm was created with
      the ability to classify epididymitis cases into three risk groups. In the Keio
      University Hospital cohort, 100%, 23.5%, and 3.4% of cases in the high-,
      intermediate-, and low-risk groups, respectively, became severe. The specificity
      of the algorithm for predicting severe epididymitis proved to be 100% in the Keio
      University Hospital cohort and 98.8% in the Tokyo Medical Center cohort. The
      decision curve analysis also showed the high efficacy of the algorithm.
      CONCLUSIONS: This algorithm might aid in decision-making for the clinical
      management of acute epididymitis.

PMID- 27714880
TI  - Facile Synthesis of Single Crystal PtSe2 Nanosheets for Nanoscale Electronics.
AB  - Ultrathin single crystal platinum diselenide (PtSe2 ) nanosheets are synthesized
      using H2 PtCl6 and Se as the precursors. The electronic properties are first
      investigated and exhibit p-type transport behavior with the mobility much larger
      than 7 cm2 V-1 s-1 . The further investigation on PtSe2 /MoS2 var der Waals p-n
      junction demonstrated that PtSe2 could be potentially applied in 2D electronics.

PMID- 27714881
TI  - Value-added reporting of specific IgE.

PMID- 27714882
TI  - A case of 'anaphylactic-like' reaction during LDL apheresis: a pathophysiological
      hypothesis on white wine containing metabisulphite.

PMID- 27714884
TI  - Coding paediatric outpatient data to provide health planners with information on
      children with chronic conditions and disabilities.
AB  - AIM: In New Zealand, there is a paucity of information on children with chronic
      conditions and disabilities (CCD). One reason is that many are managed in
      hospital outpatients where diagnostic coding of health-care events does not
      occur. This study explores the feasibility of coding paediatric outpatient data
      to provide health planners with information on children with CCD. METHODS: Thirty
      seven clinicians from six District Health Boards (DHBs) trialled coding over 12
      weeks. In five DHBs, the International Classification of Diseases and Related
      Health Problems, 10th Edition, Australian Modification (ICD-10-AM) and
      Systematised Nomenclature of Medicine Clinical Terms (SNOMED-CT) were trialled
      for 6 weeks each. In one DHB, ICD-10-AM was trialled for 12 weeks. A random
      sample (30%) of ICD-10-AM coded events were also coded by clinical coders. A mix
      of paper and electronic methods were used. RESULTS: In total 2,604 outpatient
      events were coded in ICD-10-AM and 693 in SNOMED-CT. Dual coding occurred for 770
      (29.6%) ICD-10-AM events. Overall, 34% of ICD-10-AM and 40% of SNOMED-CT events
      were for developmental and behavioural disorders. Chronic medical conditions were
      also common. Clinicians were concerned about the workload impacts, particularly
      for paper-based methods. Coder's were concerned about clinician's adherence to
      coding guidelines and the poor quality of documentation in some notes.
      CONCLUSION: Coded outpatient data could provide planners with a rich source of
      information on children with CCD. However, coding is also resource intensive.
      Thus its costs need to be weighed against the costs of managing a much larger
      health budget using very limited information.

PMID- 27714885
TI  - Knowledge and attitudes among pregnant women and maternity staff about umbilical
      cord blood banking.

PMID- 27714883
TI  - Characteristics of C-terminal, beta-amyloid peptide binding fragment of
      neuroprotective protease inhibitor, cystatin C.
AB  - Cystatin C originally identified as a cysteine proteases inhibitor has a broad
      spectrum of biological roles ranging from inhibition of extracellular cysteine
      protease activities, bone resorption, and modulation of inflammatory responses to
      stimulation of fibroblasts proliferation. There is an increasing number of
      evidence to suggest that human cystatin C (hCC) might play a protective role in
      the pathophysiology of sporadic Alzheimer's disease. In vivo and in vitro results
      well documented the association of hCC with Abeta and the hCC-induced inhibition
      of Abeta fibril formation. In our earlier work, using a combination of selective
      proteolytic methods and MS spectroscopy, C-terminal fragment hCC(101-117) was
      identified as the Abeta-binding region. The fragment of Abeta peptide responsible
      for the complex formation with hCC was found in the middle, highly hydrophobic
      part, Abeta(17-24). Structures and affinities of both Abeta and hCC binding sites
      were characterized by the enzyme-linked immunosorbent assay-like assay, by
      surface plasmon resonance, and by nano-ESI-FTICR MS of the hCC-Abeta-binding
      peptide complexes. In the in vitro inhibition studies, the binding cystatin
      sequence, hCC(101-117), revealed the highest relative inhibitory effect toward
      Abeta-fibril formation. Herein, we present further studies on molecular details
      of the hCC-Abeta complex. With Ala substitution, affinity experiments, and enzyme
      linked immunosorbent assay-like assays for the Abeta-binding fragment, hCC(101
      117), and its variants, the importance of individual amino acid residues for the
      protein interaction was evaluated. The results were analyzed using hCC(101-117)
      nuclear magnetic resonance structural data with molecular dynamics calculations
      and molecular modeling of the complexes. The results point to conformational
      requirements and special importance of some amino acid residues for the protein
      interaction. The obtained results might be helpful for the design of low
      molecular compounds modulating the biological role of both proteins. Copyright
      (c) 2016 John Wiley & Sons, Ltd.

PMID- 27714886
TI  - Pharmacokinetic and Pharmacodynamic Interaction of Andrographolide and
      Standardized Extract of Andrographis paniculata (Nees) with Nabumetone in Wistar
      Rats.
AB  - The aim of the study was to investigate the herb-drug interaction of Andrographis
      paniculata Nees (Acanthaceae) and Andrographolide (AN) with nabumetone (NAB) in
      wistar rats. Pharmacokinetic and pharmacodynamic interactions were studied after
      co-administration of APE and AN with NAB in Wistar rats. In pharmacokinetic
      studies, significant decrease in Cmax, AUC0-t and AUC0-infinity of 6-MNA after co
      administration with pure AN and APE has been observed. Tmax of 6-MNA has been
      increased to 2 h from 1.5 h in AN + NAB treated group. Changes in mean
      residential time, clearance and volume of distribution of 6-MNA in APE + NAB
      treated group and AN + NAB treated group indicated interference of other
      components of APE other than AN. In pharmacodynamic study, significant decrease
      in antiarthritic activity of NAB on concomitant administration with APE and AN
      has been observed. The study concludes that NAB exhibits pharmacokinetic and
      pharmacodynamic interactions with APE and AN in rats thus alarms the concomitant
      use of herbal preparations containing APE and AN with NAB. Further study is
      needed to understand the mechanism and predict the herb-drug interaction in
      humans. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27714888
TI  - Genetic variation of growth dynamics in maize (Zea mays L.) revealed through
      automated non-invasive phenotyping.
AB  - Hitherto, most quantitative trait loci of maize growth and biomass yield have
      been identified for a single time point, usually the final harvest stage. Through
      this approach cumulative effects are detected, without considering genetic
      factors causing phase-specific differences in growth rates. To assess the
      genetics of growth dynamics, we employed automated non-invasive phenotyping to
      monitor the plant sizes of 252 diverse maize inbred lines at 11 different
      developmental time points; 50 k SNP array genotype data were used for genome-wide
      association mapping and genomic selection. The heritability of biomass was
      estimated to be over 71%, and the average prediction accuracy amounted to 0.39.
      Using the individual time point data, 12 main effect marker-trait associations
      (MTAs) and six pairs of epistatic interactions were detected that displayed
      different patterns of expression at various developmental time points. A subset
      of them also showed significant effects on relative growth rates in different
      intervals. The detected MTAs jointly explained up to 12% of the total phenotypic
      variation, decreasing with developmental progression. Using non-parametric
      functional mapping and multivariate mapping approaches, four additional marker
      loci affecting growth dynamics were detected. Our results demonstrate that plant
      biomass accumulation is a complex trait governed by many small effect loci, most
      of which act at certain restricted developmental phases. This highlights the need
      for investigation of stage-specific growth affecting genes to elucidate important
      processes operating at different developmental phases.

PMID- 27714887
TI  - Highly Stretchable, Strain Sensing Hydrogel Optical Fibers.
AB  - A core-clad fiber made of elastic, tough hydrogels is highly stretchable while
      guiding light. Fluorescent dyes are easily doped into the hydrogel fiber by
      diffusion. When stretched, the transmission spectrum of the fiber is altered,
      enabling the strain to be measured and also its location.

PMID- 27714889
TI  - COMPARISON BETWEEN PROTON MAGNETIC RESONANCE SPECTROSCOPY FINDINGS IN DOGS WITH
      TICK-BORNE ENCEPHALITIS AND CLINICALLY NORMAL DOGS.
AB  - In vivo diagnosis of tick-borne encephalitis is difficult due to high
      seroprevalence and rapid viral clearance, limiting detection of antibodies in
      blood and cerebrospinal fluid. Magnetic resonance imaging (MRI) characteristics
      of tick-borne encephalitis have been reported, however MRI studies can also be
      negative despite the presence of neurologic signs. Magnetic resonance
      spectroscopy (1 H MRS) is an imaging method that provides additional information
      about the metabolic characteristics of brain tissues. The purpose of this
      retrospective cross-sectional study was to describe brain metabolites using short
      echo time single-voxel 1 H MRS in dogs with confirmed tick-borne encephalitis and
      compare them with healthy dogs. Inclusion criteria for the affected dogs were
      neurological symptoms suggestive of tick-borne encephalitis, previous endemic
      stay and tick-bite, diagnostic quality brain MRI and 1 H MRS studies, and
      positive antibody titers or confirmation of tick-borne encephalitis with
      necropsy. Control dogs were 10, clinically normal beagles that had been used in a
      previous study. A total of six affected dogs met inclusion criteria. All dogs
      affected with tick-borne encephalitis had 1 H MRS metabolite concentration
      alterations versus control dogs. These changes included mild to moderate
      decreases in N-acetyl aspartate and creatine peaks, and mild increases in
      glutamate/glutamine peaks. No lactate or lipid signal was detected in any dog.
      Myoinositol and choline signals did not differ between affected and control dogs.
      In conclusion, findings supported the use of 1 H MRS as an adjunctive imaging
      method for dogs with suspected tick-borne encephalitis and inconclusive
      conventional MRI findings.

PMID- 27714890
TI  - Chronic odorant exposure upregulates acquisition of functional properties in
      cultured embryonic chick olfactory sensory neurons.
AB  - Neuronal development and differentiation is modulated by activity-dependent
      mechanisms that stimulate endogenous neurogenesis and differentiation to promote
      adaptive survival of the organism. Studies on bird odor imprinting have shown how
      sensory stimuli or environmental influences can affect neonatal behavior,
      presumably by remodeling the developing nervous system. It is unclear whether
      these changes originate from the sensory neurons themselves or from the brain.
      Thus, we attempted to address this by using an in vitro system to separate the
      peripheral neurons from their central connections. Olfactory neurons from
      embryonic day 17 Gallus domesticus chicks were isolated, cultured, and exposed to
      100 uM amyl acetate or phenethyl alcohol in 12-hr bouts, alternated with periods
      of no-odor exposure. On days 4 and 5 in vitro, cells were immunostained for
      olfactory marker protein, neuron-specific tubulin, and olfactory GTP-binding
      protein, and tested for odorant sensitivity using calcium imaging. While odorant
      exposure did not result in a significant increase in the overall number of
      neurons, it promoted neuron differentiation: a larger proportion of odorant
      exposed cells expressed olfactory marker protein and the olfactory GTP-binding
      protein. When cell responsiveness was tested using calcium imaging, a greater
      proportion of odorant-exposed cells responded to stimulation with 100 uM amyl
      acetate or phenethyl alcohol. Thus, odorant exposure during development modulated
      the developmental trajectories of individual neurons, resulting in changes in
      protein expression associated with odorant signaling. This suggests that the
      neuronal changes in the periphery have an important contribution to the overall
      long-term functional changes associated with odor imprinting. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27714891
TI  - A Novel Approach to Treating CFS and Co-morbid Health Anxiety: A Case Study.
AB  - OBJECTIVES: Chronic Fatigue Syndrome (CFS) is a debilitating condition that
      affects 0.2-0.4% of the population. First-line treatments are Cognitive Behaviour
      Therapy or graded exercise therapy; however, these treatments yield only moderate
      effect sizes. Emerging research suggests that anxiety about health may be common
      in CFS. Health anxiety treatment models demonstrate good therapeutic outcomes;
      however, these models have yet to be applied to CFS. This paper describes the
      application of a novel cognitive behavioural approach to the treatment of both
      physical and anxiety related symptoms in a patient with CFS and, furthermore,
      presents a conceptual hypothesis regarding the mutually maintaining relationship
      between these two co-occurring conditions. DESIGN: A single-case design was used,
      with pre-data, post-data and follow-up data. The cognitive behavioural model of
      health anxiety was adapted and delivered as an eight-session intervention. The
      intervention was driven by an individualized formulation developed
      collaboratively with the patient. RESULTS: The application of this approach
      generated reliable and clinically significant reductions in physical and
      psychological symptoms, which were maintained at 12-month follow-up. The
      participant no longer fulfilled the criteria for CFS or health anxiety following
      eight treatment sessions. The treatment approach was found to be agreeable to the
      patient. All treatment hypotheses were supported. CONCLUSIONS: An adapted
      cognitive behavioural approach to treating CFS and health anxiety yields positive
      results and shows promise for application to the broader CFS population.
      Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGES: Chronic
      Fatigue Syndrome (CFS) is a debilitating condition that is difficult to treat
      successfully; first-line recommended treatments achieve only moderate effect
      sizes. Anxiety, particularly about health, is reported to be common in CFS.
      However, anxiety is not specifically targeted within treatment and may negatively
      influence outcome due to the potentially mutually maintaining nature of these
      complex conditions. The present study demonstrates that an integrated treatment
      approach designed to encompass physical and psychological symptoms yields
      reliable and clinically significant outcomes in 50% of time recommend for first
      line treatments. Results reflected non-case level status for both CFS and health
      anxiety at end of treatment, in addition to reductions across all clinical
      measures. This study demonstrates the fundamental importance of an
      individualized, rather than generic, treatment approach to complex cases; the
      'meaning' of experience is a central tenet within a cognitive approach that
      should be reflected in treatment.

PMID- 27714892
TI  - The Partners in Health scale for older adults: design and examination of its
      psychometric properties in a Dutch population of older adults.
AB  - BACKGROUND: Self-management is an important asset in helping older adults remain
      independent and in control for as long as possible. There is no reliable and
      valid measurement instrument to evaluate self-management behaviour of older
      adults. OBJECTIVE: This study aims to design a measurement instrument, that is
      the Partners in Health scale for older adults (PIH-OA), to assess self-management
      knowledge and behaviour of community-living older adults and to examine its
      psychometric properties in a Dutch context. METHODS/DESIGN: The original PIH
      scale was translated into Dutch and adapted to the context of community-living
      older adults, resulting in the PIH-OA. Data for 1127 participants (mean age 81.7,
      SD=4.5) from the Embrace study were used to assess the psychometric properties.
      RESULTS: Data fitted a three-factor model, covering the constructs Knowledge,
      Management and Coping, with good internal consistencies (Cronbach's alphas
      ranging from .77 to .84). Known groups validity was confirmed: no differences
      were found between gender, age and marital status groups, and differences were
      found between the education level and health status groups. Discriminant validity
      was confirmed by weak correlations between PIH-OA scales and scales evaluating
      "Perceived integrated care" and "Activities of daily living (ADL)" (r<.30), and a
      moderate correlation between the PIH-OA subscale "Coping" and the scale
      evaluating "ADL" (r=.41). CONCLUSION: The PIH-OA appears to be a reliable and
      valid measurement instrument for assessing the self-management knowledge and
      behaviour of older adults. This could help professionals provide tailored support
      to improve the well-being and independence of older adults.

PMID- 27714893
TI  - Ethnic disparities in infectious disease hospitalisations in the first year of
      life in New Zealand.
AB  - AIM: Infectious disease (ID) hospitalisation rates are increasing in New Zealand
      (NZ), especially in pre-school children, and Maori and Pacific people. We aimed
      to identify risk factors for ID hospitalisation in infancy within a birth cohort
      of NZ children, and to identify differences in risk factors between ethnic
      groups. METHODS: We investigated an established cohort of 6846 NZ children, born
      in 2009-2010, with linkage to a national data set of hospitalisations. We used
      multivariable logistic regression to obtain odds ratios (OR) for factors
      associated with ID hospitalisation in the first year of life, firstly for all
      children, and then separately for Maori or Pacific children. RESULTS: In the
      whole cohort, factors associated with ID hospitalisation were Maori (OR: 1.49,
      95% CI: 1.17-1.89) or Pacific (2.51; 2.00-3.15) versus European maternal
      ethnicity, male gender (1.32; 1.13-1.55), low birthweight (1.94, 1.39-2.66),
      exclusive breastfeeding for <4 months (1.22, 1.04-1.43), maternal experience of
      health-care racism (1.60, 1.19-2.12), household deprivation (most vs. least
      deprived quintile of households (1.50, 1.12-2.02)), day-care attendance (1.43,
      1.12-1.81) and maternal smoking (1.55, 1.26-1.91). Factors associated with ID
      hospitalisation for Maori infants were high household deprivation (2.16, 1.06
      5.02) and maternal smoking (1.48, 1.02-2.14); and for Pacific infants were
      delayed immunisation (1.72, 1.23-2.38), maternal experience of health-care racism
      (2.20, 1.29-3.70) and maternal smoking (1.59, 1.10-2.29). CONCLUSIONS: Maori and
      Pacific children in NZ experience a high burden of ID hospitalisation. Some risk
      factors, for example maternal smoking, are shared, while others are ethnic
      specific. Interventions aimed at preventing ID hospitalisations should address
      both shared and ethnic-specific factors.

PMID- 27714894
TI  - Peri-prosthetic tissue cells show osteogenic capacity to differentiate into the
      osteoblastic lineage.
AB  - During the process of aseptic loosening of prostheses, particulate wear debris
      induces a continuous inflammatory-like response resulting in the formation of a
      layer of fibrous peri-prosthetic tissue at the bone-prosthesis interface. The
      current treatment for loosening is revision surgery which is associated with a
      high-morbidity rate, especially in old patients. Therefore, less invasive
      alternatives are necessary. One approach could be to re-establish
      osseointegration of the prosthesis by inducing osteoblast differentiation in the
      peri-prosthetic tissue. Therefore, the aim of this study was to investigate the
      capacity of peri-prosthetic tissue cells to differentiate into the osteoblast
      lineage. Cells isolated from peri-prosthetic tissue samples (n = 22)-obtained
      during revision surgeries-were cultured under normal and several osteogenic
      culture conditions. Osteogenic differentiation was assessed by measurement of
      Alkaline Phosphatse (ALP), mineralization of the matrix and expression of several
      osteogenic genes. Cells cultured in osteogenic medium showed a significant
      increase in ALP staining (p = 0.024), mineralization of the matrix (p < 0.001)
      and ALP gene expression (p = 0.014) compared to normal culture medium. Addition
      of bone morphogenetic proteins (BMPs), a specific GSK3beta inhibitor (GIN) or a
      combination of BMP and GIN to osteogenic medium could not increase ALP staining,
      mineralization, and ALP gene expression. In one donor, addition of GIN was
      required to induce mineralization of the matrix. Overall, we observed a high
      inter-donor variability in response to osteogenic stimuli. In conclusion, peri
      prosthetic tissue cells, cultured under osteogenic conditions, can produce
      alkaline phosphatase and mineralized matrix, and therefore show characteristics
      of differentiation into the osteoblastic lineage. (c) 2016 The Authors. Journal
      of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of
      Orthopaedic Research Society. J Orthop Res 35:1732-1742, 2017.

PMID- 27714895
TI  - Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked
      With Amyotrophic Lateral Sclerosis.
AB  - Research in recent years has extensively investigated the therapeutic efficacy of
      mesenchymal stromal cells in regenerative medicine for many neurodegenerative
      diseases at preclinical and clinical stages. However, the success rate of stem
      cell therapy remains less at translational phase. Lack of relevant animal models
      that potentially simulate the molecular etiology of human pathological symptoms
      might be a reason behind such poor clinical outcomes associated with stem cell
      therapy. Apparently, self-renewal and differentiation ability of mesenchymal stem
      cells may help to study the early developmental signaling pathways connected with
      the diseases, such as Alzheimer's disease, Amyotrophic lateral sclerosis (ALS),
      etc., at in vitro level. Cannabidiol, a non-psychotrophic cannabinoid, has been
      demonstrated as a potent anti-inflammatory and neuroprotective agent in
      neurological preclinical models. In the present study, we investigated the
      modulatory role of cannabidiol on genes associated with ALS using human gingiva
      derived mesenchymal stromal cells (hGMSCs) as an in vitro model system. Next
      generation transcriptomic sequencing analysis demonstrated considerable
      modifications in the expression of genes connected with ALS pathology, oxidative
      stress, mitochondrial dysfunction, and excitotoxicity in hGMSCs treated with
      cannabidiol. Our results suggest the efficacy of cannabidiol to delineate the
      unknown molecular pathways, which may underlie ALS pathology at an early stage
      using hGMSCs as a compelling in vitro system. J. Cell. Biochem. 118: 819-828,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27714896
TI  - Comparing calculated free testosterone with total testosterone for screening and
      diagnosing late-onset hypogonadism in aged males: A cross-sectional study.
AB  - OBJECTIVE: The aim of this study is to compare calculated free testosterone (cFT)
      and total testosterone (T) in predicting late-onset hypogonadism (LOH) in middle
      aged and elderly males. METHODS: We surveyed a random sample of 608 males between
      the ages of 45 and 87 years from Shanghai, China. The Aging Male Symptoms (AMS)
      questionnaire and the Androgen Deficiency in Aging Male (ADAM) questionnaire were
      completed by the subjects. Testosterone (T), sex hormone-binding globulin (SHBG),
      albumin, and other blood biochemical indexes were measured in 332 males. The
      corresponding cFT was obtained using the Vermeulen formula and the correlations
      between T and cFT were analyzed by SPSS statistical software. RESULTS: Among the
      332 males who underwent biochemical evaluation, 289 males (87.0%) was positively
      screened by the ADAM questionnaire and 232 males (69.9%) by the AMS
      questionnaire. As suggested by linear regression, cFT exhibited a negative
      correlation with age in both ADAM+ and AMS+ group, whereas T did not appear to
      have significant correlation with age. Besides, there were statistically
      significant differences in cFT (P<.001) in the AMS questionnaire. CONCLUSIONS:
      Calculated free testosterone levels are more reliable than T levels for
      diagnosing LOH in middle-aged and elderly males.

PMID- 27714898
TI  - Review of cytomegalovirus coinfection in HIV-infected individuals in Africa.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection among HIV-infected individuals may
      cause end-organ disease, which is an AIDS-defining condition. Evidence from high
      income countries suggests that CMV may alter the outcome of HIV infection, other
      than causing end-organ diseases. We reviewed literature on HIV and CMV
      coinfection in Africa. METHODS: Systematic review of published studies on HIV and
      CMV coinfection in Africa using the PubMed database. RESULTS: High CMV
      seroprevalence was found throughout Africa, exceeding 90% in most populations.
      Retinitis, pneumonia, and colitis were the most commonly reported CMV
      manifestations in HIV-infected individuals. Among patients with pulmonary
      symptoms, the prevalence of CMV pneumonitis varied from 20% to over 60%, whereas
      CMV was found in 0% to 14% of patients with gastrointestinal manifestations.
      Cytomegalovirus retinitis was found in 0% to 2.6% of examined HIV-infected
      individuals. The diagnostics of CMV end-organ diseases were found complex and
      difficult to interpret in African settings. Cytomegalovirus viremia was
      correlated with significantly lower CD4 cell count and increase in activated and
      apoptosis vulnerable T-lymphocytes. Also, CMV coinfection was found to be
      associated with increased transmission and progression of HIV infection.
      Moreover, detectable CMV DNA was an independent predictor of HIV transmission and
      mortality among HIV-infected individuals. CONCLUSIONS: Cytomegalovirus is highly
      prevalent in Africa and a common cause of disease manifestations in HIV-infected
      individuals among all age groups. Cytomegalovirus coinfection in HIV-infected
      individuals in Africa is associated with increased transmission and mortality of
      HIV, but it is a neglected area of research.

PMID- 27714897
TI  - Development and Validation of a Novel Laboratory-Specific Correction Equation for
      Total Serum Calcium and Its Association With Mortality Among Hemodialysis
      Patients.
AB  - Conventional albumin-corrected calcium is inaccurate in predicting ionized
      calcium, and hidden hypercalcemia, characterized as high ionized calcium with
      normal total calcium, is associated with higher mortality in hemodialysis
      patients. By using a national cohort of hemodialysis patients in the Unites
      States, a novel laboratory-specific prediction equation composed of total
      calcium, albumin, and phosphorus was derived from 242 patients in the South
      Atlantic division (adjusted R2  = 0.80 versus 0.71 for the conventional equation)
      and then validated among 566 patients in the other divisions (adjusted R2  = 0.79
      versus 0.68 for the conventional equation). Compared with the conventional
      equation, the novel equation showed a greater correlation with intact parathyroid
      hormone. Its relative performance against the conventional equation was
      consistent across subgroups based on medications related to calcium metabolism.
      The novel equation also had a higher sensitivity (57% versus 34%) and an
      equivalent specificity (99% versus 100%) against ionized hypercalcemia at a cut
      off value of 10.2 mg/dL. Sensitivity and specificity at 9.4 mg/dL was 94% and 76%
      (versus 87% and 82% for the conventional equation), respectively. A survival
      analysis in 87,779 incident hemodialysis patients showed that among patients who
      were categorized as having a high-normal calcium status (ie, >9.4 to 10.2 mg/dL)
      by the conventional equation, there appeared a trend toward higher adjusted
      mortality risk across higher calcium status defined according to the novel
      equation. Meanwhile, the mortality risk was consistent across calcium strata
      defined according to the conventional equation within the categories defined by
      the novel equation. In conclusion, in comparison to the conventional equation, a
      novel laboratory-specific correction equation derived for correction of total
      calcium performs significantly better in ascertaining hidden hypercalcemia in
      hemodialysis patients, and aids in identifying patients at higher risk for
      mortality. (c) 2016 American Society for Bone and Mineral Research.

PMID- 27714899
TI  - Ulcerated plaque of coronary artery: Insights from ex vivo images of optical
      frequency domain imaging and histopathology.

PMID- 27714900
TI  - Length-Independent Charge Transport in Chimeric Molecular Wires.
AB  - Advanced molecular electronic components remain vital for the next generation of
      miniaturized integrated circuits. Thus, much research effort has been devoted to
      the discovery of lossless molecular wires, for which the charge transport rate or
      conductivity is not attenuated with length in the tunneling regime. Herein, we
      report the synthesis and electrochemical interrogation of DNA-like molecular
      wires. We determine that the rate of electron transfer through these constructs
      is independent of their length and propose a plausible mechanism to explain our
      findings. The reported approach holds relevance for the development of high
      performance molecular electronic components and the fundamental study of charge
      transport phenomena in organic semiconductors.

PMID- 27714901
TI  - Fusaricidins from Paenibacillus polymyxa M-1, a family of lipohexapeptides of
      unusual complexity-a mass spectrometric study.
AB  - Paenibacillus polymyxa are rhizobacteria with a high potential to produce natural
      compounds of biotechnological and medical interest. Main products of P. polymyxa
      are fusaricidins, a large family of antifungal lipopeptides with a 15-guanidino-3
      hydroxypentadecanoic acid (GHPD) as fatty acid side chain. We use the P. polymyxa
      strain M-1 as a model organism for the exploration of the biosynthetic potential
      of these rhizobacteria. Using matrix-assisted laser-desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) about 40 new fusaricidins were detected
      which were fractionated by reversed-phase (rp) HPLC. Their structure was
      determined by MALDI-LIFT-TOF/TOF fragment analysis. The dominant fragment in the
      product ion spectra of fusaricidins appeared at m/z 256.3, 284.3 and 312.4,
      respectively, indicating variations in their fatty acid part. Two new subfamilies
      of fusaricidins were introduced which contain guanidino-3-hydroxyhepta- and
      nonadecanoic acid as fatty acid constituents. Apparently, the end-standing
      guanidine group is not modified as shown by direct infusion nano-electrospray
      ionization mass spectrometry (nano-ESI MS). The results of this study suggest
      that advanced mass spectrometry is the method of choice for investigating natural
      compounds of unusual diversity, like fusaricidins. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27714902
TI  - Factors associated with HIV status awareness and Linkage to Care following home
      based testing in rural Malawi.
AB  - OBJECTIVE: HIV diagnosis and linkage to care are the main barriers in Africa to
      achieving the UNAIDS 90-90-90 targets. We assessed HIV-positive status awareness
      and linkage to care among survey participants in Chiradzulu District, Malawi.
      METHOD: Nested cohort study within a population-based survey of persons aged 15
      59 years between February and May 2013. Participants were interviewed and tested
      for HIV (and CD4 if found HIV-positive) in their homes. Multivariable regression
      was used to determine factors associated with HIV-positive status awareness prior
      to the survey and subsequent linkage to care. RESULTS: Of 8277 individuals
      eligible for the survey, 7270 (87.8%) participated and were tested for HIV. The
      overall HIV prevalence was 17.0%. Among HIV-positive participants, 77.0% knew
      their status and 72.8% were in care. Women (adjusted odds ratio [aOR] 6.5, 95% CI
      3.2-13.1) and older participants (40-59 vs. 15-29 years, aOR 10.1, 95% CI 4.0
      25.9) were more likely to be aware of their positive status. Of those newly
      diagnosed, 47.5% were linked to care within 3 months. Linkage to care was higher
      among older participants (40-59 vs. 15-29, adjusted hazard ratio [aHR] 3.39, 95%
      CI 1.83-6.26), women (aHR 1.73, 95% CI 1.12-2.67) and those eligible for ART (aHR
      1.61, 95% CI 1.03-2.52). CONCLUSIONS: In settings with high levels of HIV
      awareness, home-based testing remains an efficient strategy to diagnose and link
      to care. Men were less likely to be diagnosed, and when diagnosed to link to
      care, underscoring the need for a gender focus in order to achieve the 90-90-90
      targets.

PMID- 27714905
TI  - Power-to-Syngas: An Enabling Technology for the Transition of the Energy System?
AB  - Power-to-X concepts promise a reduction of greenhouse gas emissions
      simultaneously guaranteeing a safe energy supply even at high share of renewable
      power generation, thus becoming a cornerstone of a sustainable energy system.
      Power-to-syngas, that is, the electrochemical conversion of steam and carbon
      dioxide with the use of renewably generated electricity to syngas for the
      production of synfuels and high-value chemicals, offers an efficient technology
      to couple different energy-intense sectors, such as "traffic and transportation"
      and "chemical industry". Syngas produced by co-electrolysis can thus be regarded
      as a key-enabling step for a transition of the energy system, which offers
      additionally features of CO2 -valorization and closed carbon cycles. Here, we
      discuss advantages and current limitations of low- and high-temperature co
      electrolysis. Advances in both fundamental understanding of the basic reaction
      schemes and stable high-performance materials are essential to further promote co
      electrolysis.

PMID- 27714904
TI  - Successful participation of patients in interprofessional team meetings: A
      qualitative study.
AB  - BACKGROUND: The number of people with multiple chronic conditions increases as a
      result of ageing. To deal with the complex health-care needs of these patients,
      it is important that health-care professionals collaborate in interprofessional
      teams. To deliver patient-centred care, it is often recommended to include the
      patient as a member of the team. OBJECTIVE: To gain more insight into how health
      care professionals and patients, who are used to participate in interprofessional
      team meetings, experience and organize patient participation in the team
      meetings. METHODS: A qualitative study including observations of meetings (n=8),
      followed by semi-structured interviews with participating health-care
      professionals (n=8), patients and/or relatives (n=11). Professionals and patients
      were asked about their experiences of patient participation immediately after the
      team meetings. Results from both observations and interviews were analysed using
      content analysis. RESULTS: The findings show a variety of influencing factors
      related to patient participation that can be divided into five categories: (i)
      structure and task distribution, (ii) group composition, (iii) relationship
      between professionals and patients or relatives, (iv) patients' characteristics
      and (v) the purpose of the meeting. CONCLUSION: Patient participation during team
      meetings was appreciated by professionals and patients. A tailored approach to
      patient involvement during team meetings is preferable. When considering the
      presence of patients in team meetings, it is recommended to pay attention to
      patients' willingness and ability to participate, and the necessary information
      shared before the meeting. Participating patients seem to appreciate support and
      preparation for the meeting.

PMID- 27714903
TI  - Risk factors for ocular surface squamous neoplasia in Kenya: a case-control
      study.
AB  - OBJECTIVE: To determine modifiable risk factors of ocular surface squamous
      neoplasia (OSSN) in Kenya using disease-free controls. METHODS: Adults with
      conjunctival lesions were recruited at four eye care centres in Kenya and
      underwent excision biopsy. An equal number of controls having surgery for
      conditions not affecting the conjunctiva and unrelated to ultraviolet light were
      group-matched to cases by age group, sex and eye care centre. Associations of
      risk factors with OSSN were evaluated using multivariable logistic regression to
      estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Continuous
      variables were compared using the t-test or the Wilcoxon-Mann-Whitney U-test
      depending on their distribution. RESULTS: A total of 131 cases and 131 controls
      were recruited. About two-thirds of participants were female, and the mean age of
      cases and controls was 42.1 years and 43.3 years, respectively. Risk factors for
      OSSN were HIV infection without antiretroviral therapy (ART) use (OR = 48.42; 95%
      CI: 7.73-303.31) and with ART use (OR = 19.16; 95% CI: 6.60-55.57), longer
      duration of exposure to the sun in the main occupation (6.9 h/day vs. 4.6 h/day,
      OR = 1.24; 95% CI: 1.10-1.40) and a history of allergic conjunctivitis (OR =
      74.61; 95% CI: 8.08-688.91). Wearing hats was protective (OR = 0.22; 95% CI: 0.07
      0.63). CONCLUSION: Measures to prevent and control HIV, reduce sun exposure such
      as wearing hats and control allergic conjunctivitis are recommended.

PMID- 27714906
TI  - Retrospective evaluation of blood copper stable isotopes ratio 65 Cu/63 Cu as a
      biomarker of cancer in dogs.
AB  - Previous studies in humans with breast, colorectal or liver cancer showed that
      neoplasia was associated with a modification of the blood ratio between 65 Cu and
      63 Cu (?Cu). The aim of the present study was to compare the blood ?Cu of dogs
      with cancer to healthy controls or dogs with non-oncologic disease. One hundred
      and seventeen dogs were included in the study (35 dogs with cancer, 33 dogs with
      non-neoplastic disease, and 49 healthy controls). The ?Cu of dogs with cancer was
      significantly lower than the ratio of healthy controls (P < 0.0001) but not
      significantly different from dogs with non-oncologic disease. Six dogs with
      lymphoma were also evaluated after they achieved clinical remission and five out
      of six had an increase of ?Cu. Further studies are warranted but these results
      suggest that ?Cu could help in the diagnosis of cancer in a controlled clinical
      context, and may be a potential biomarker for the follow-up of cancer.

PMID- 27714908
TI  - Lymph node histology for the assessment of residual neoplastic disease in canine
      mast cell tumours: does the presence of metachromatic granules always identify
      mast cells?

PMID- 27714907
TI  - The use and modification of injury prevention exercises by professional youth
      soccer teams.
AB  - The efficacy of injury prevention exercise programs (IPEPs) for amateur youth
      soccer has been established, but little is known about their adaptability to
      other soccer populations. This study aimed to assess the use of individual injury
      prevention exercises by professional youth soccer teams, against the industry
      standard, FIFA 11+ program. Four teams' chosen IPEPs were observed across one
      season and documented on a standardized form. The use of each FIFA 11+ exercise
      was coded as "performed", "performed modified" or "not performed". The proportion
      of the 160 observed sessions containing each individual exercise was calculated.
      Staff provided reasons for their use and modification of FIFA 11+ exercises. On
      average, individual FIFA 11+ exercises were conducted in original form in 12% of
      the sessions (range 0-33%), and in modified form in 28% of sessions (range 2
      62%). The five most frequently observed exercises, in either original or modified
      form, were "bench" (72%), "squats" (69%), "running straight" (68%), "single-leg
      stance" (66%), and "sideways bench" (64%). Staff modified exercises to add
      variation, progression, and individualization, and to align with specific
      training formats and goals. Professional youth soccer teams often use injury
      prevention exercises similar to those in the FIFA 11+, but tailor them
      considerably to fit their implementation context.

PMID- 27714910
TI  - Changes in leisure-time physical activity and physical and mental health
      functioning: a follow-up study.
AB  - Functioning will be an increasingly important issue in Finland over the coming
      decades as the proportion of the population aged 65 and older is growing
      significantly. However, the associations between changes in physical activity and
      subsequent health functioning are poorly understood. The aim of this study was to
      examine how changes in physical activity relate to concurrent and prospective
      levels of health functioning. Cohort data from the Helsinki Health Study were
      used. Phase 1 (n = 8960, response rate 67%, 80% women) was conducted among 40- to
      60-year-old employees of the City of Helsinki in 2000-2002, phase 2 in 2007 (n =
      7332, response rate 83%), and phase 3 in 2012 (n = 6814, response rate 79%).
      Linear mixed models were used as the main statistical method. Increasing physical
      activity was associated with higher concurrent and prospective levels of physical
      health functioning, whereas decreasing activity was associated with lower levels
      of physical health functioning. The associations were stronger with physical than
      with mental health functioning. Promoting physical activity among aging people
      may help to maintain their level of health functioning.

PMID- 27714909
TI  - Influence of altitude on local adaptation in upland tree species from central
      Argentina.
AB  - Steep climatic gradients boost morphological and physiological adjustments in
      plants, with consequences on performance. The three principal woody species of
      the Sierras Grandes Mountains of central Argentina have marked differences in
      sapling performance along their altitudinal distribution. We hypothesize that the
      steep gradient of climatic conditions across the species' altitudinal
      distribution promotes trait differences between populations of different
      altitudes that are inherited by the following generation. Seeds from different
      altitudes were exposed to three temperature regimes to assess differential
      germination responses. Saplings were then transplanted to a greenhouse to assess
      possible variations in attributes and performance after 18 months. The three
      species showed differences in germination responses to temperature among
      altitudes and/or in sapling attributes and performance. In Maytenus boaria and
      Escallonia cordobensis, germination success was higher under high temperatures
      for the highest-altitude, whereas lower temperatures boosted germination of the
      lowest altitudes. Polylepis australis showed no differences in germination among
      temperature treatments. In the greenhouse, saplings of the three species from
      intermediate altitudes showed high performance, whereas the upper and lower
      populations seemed to be adjusted to tolerating more stressful conditions (i.e.,
      lower temperatures at the upper end and water stress at the lower end), showing
      lower performance toward both altitudinal limits. These patterns agree with those
      described for saplings growing under field conditions, suggesting adjustments in
      response to environmental changes undergone by populations along the altitudinal
      range. The marked adjustments of populations to the local environment suggest a
      potentially high impact of climatic change on species distribution.

PMID- 27714911
TI  - Effects of group sports on health-related physical fitness of overweight youth: A
      systematic review and meta-analysis.
AB  - Group sports interventions have been developed to improve health-related physical
      fitness of overweight/obese youth. However, its benefits are not systematically
      documented. This study synthesizes the evidence about the effects of group sports
      on health-related physical fitness of overweight/obese youth. Pubmed, Web of
      Knowledge, Scopus, Medline, CINAHL, SportDiscus, and Academic Search Complete
      were searched in February 2016. Studies assessing the effects of group sports on
      body composition, cardiorespiratory endurance, muscle strength, flexibility, and
      neuromotor fitness of overweight/obese youth (aged <18 years) were included.
      Effect sizes (ES) were calculated with Cohen's d and its 95% confidence intervals
      (CI). Improvements were found in (i) body composition - percentage of fat body
      mass (pooled ES = 0.67; 95% CI = 0.24-1.10) and waist circumference (ES = 0.69; P
      = 0.004); (ii) cardiorespiratory endurance - peak oxygen consumption (pooled ES =
      0.53; 95% CI = 0.13-0.92) and (iii) muscle strength - hand grip strength (ES =
      0.72; P = 0.003). No significant effects were found for body mass index (pooled
      ES = 0.27; 95% CI = -0.14 to 0.69), percentage of lean body mass (ES = 0.01; P >
      0.05), maximal power output (ES from 0 to 0.06; P > 0.05), sit-and-reach test
      (pooled ES = 0.26; 95% CI = -0.16 to 0.68) and agility test (ES = 0; P = 0.48).
      Group sports improve body composition, cardiorespiratory endurance, and hand grip
      strength of overweight/obese youth. Flexibility and neuromotor fitness do not
      seem to change following group sports.

PMID- 27714912
TI  - On the TRAIL to truth, or on a road to nowhere?

PMID- 27714913
TI  - Photon Driven Transformation of Cesium Lead Halide Perovskites from Few-Monolayer
      Nanoplatelets to Bulk Phase.
AB  - Influence of light exposure on cesium lead halide nanostructures has been
      explored. A discovery of photon driven transformation (PDT) in 2D CsPbBr3
      nanoplatelets is reported, in which the quantum-confined few-monolayer
      nanoplatelets will convert to bulk phase under very low irradiation intensity
      (~20 mW cm-2 ). Benefiting from the remarkable emission color change during PDT,
      the multicolor luminescence photopatterns and facile information photo-encoding
      are established.

PMID- 27714914
TI  - A pilot study of potential brain donor satisfaction and attitudes towards
      telephone assessment.
AB  - OBJECTIVE: Test the feasibility of assessing cognition, psychiatric symptoms and
      daily living skills of potential brain donors by telephone and compare
      satisfaction and attitudes across telephone and face-to-face assessment. METHOD:
      Data were collected from 108 healthy participants from the Brains for Dementia
      Research cohort. Purposive sampling was used to assess feasibility and a
      randomised control trial design compared satisfaction and attitudes towards
      telephone and face-to-face assessment. Non-parametric tests were conducted to
      compare groups, and logistic regression was performed to assess the relationship
      between satisfaction and participant characteristics. RESULTS: Of the 80
      participants offered telephone assessment, 67 (83.8%) agreed, 2 (2.5%) had a
      significant hearing impairment, 4 (5.0%) had potential memory problems and 7
      (8.7%) declined. On average, telephone assessments lasted 38 min and duration was
      negatively associated with Telephone Interview of Cognitive Status-Modified
      scores (p = 0.001) and positively associated with age (p = 0.040),
      Neuropsychiatric Inventory scores (p = 0.019), Geriatric Depression Scale (p =
      0.035) and Global Deterioration Scale (p = 0.022). Satisfaction was high in
      respect to organisational and personal aspects; ratings did not differ
      significantly across telephone and face-to-face assessment groups and were not
      related to socio-demographic characteristics. Participants undergoing telephone
      assessment were significantly more likely to hold positive attitudes towards this
      mode of assessment. CONCLUSIONS: Telephone assessment is feasible, time-efficient
      and acceptable to healthy, potential brain donors. When used with other
      assessment modes and within the context of established contact, telephone
      assessment offers greater flexibility to researchers and participants and
      represents an effective mechanism for overcoming the challenges of growing,
      ageing cohorts and uncertain resources. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 27714915
TI  - Classifying skin diseases: Until where should we go?
AB  - New molecular mapping techniques appear to allow clinicians to design treatments
      in some cases of resisting cancers. Such sensitive analysis were already able to
      depict molecular pathways of several inflammatory skin diseases. An accompanying
      article by Garzorz-Stark et al. show how these tools could improve the
      classification of skin inflammatory diseases now based on clinical and
      pathological features. At last, the final aim of these tools is to predict
      treatment response in a patient. The utility of "precision" or personalized
      medicine in cutaneous inflammatory diseases could join the furrow drawn in
      cancer.

PMID- 27714916
TI  - Evaluation of systemic neonicotinoid insecticides for the management of the Asian
      citrus psyllid Diaphorina citri on containerized citrus.
AB  - BACKGROUND: Studies were conducted to evaluate uptake and retention of three
      systemic neonicotinoid insecticides, dinotefuran, imidacloprid and thiamethoxam,
      in potted citrus nursery plants treated at standard label rates. Infestation of
      these plants placed at a field site with moderate levels of Asian citrus psyllid
      (ACP) was monitored for 14 weeks following treatments, and insecticide residues
      in leaf tissue were quantified using enzyme-linked immunosorbent assay (ELISA).
      Bioassays were conducted using leaves harvested on various dates post-treatment
      to compare the efficacies of residues against adult ACP. RESULTS: Residues of the
      three neonicotinoids were detected in leaf tissues within 1 week after treatment.
      Peak concentrations established at 1 week for imidacloprid and dinotefuran and at
      2 weeks for thiamethoxam. Imidacloprid and thiamethoxam outperformed the control
      and dinotefuran treatments at protecting trees from infestations by ACP eggs and
      nymphs. For a given insecticide concentration in leaf tissue, thiamethoxam
      induced the highest mortality of the three insecticides, and dinotefuran was the
      least toxic. CONCLUSION: If the time needed to achieve effective thresholds of a
      systemic neonicotinoid is known, treatments at production facilities could be
      scheduled that would minimize unnecessary post-treatment holding periods and
      ensure maximum retention of effective concentrations after the plants have
      shipped to retail outlets. The rapid uptake of the insecticides and retention at
      effective concentrations in containerized citrus suggest that the current 30 day
      post-treatment shipping restriction from production facilities to retail outlets
      outside of quarantine could be shortened to 14 days. Thiamethoxam should be added
      to the list of approved nursery treatments. (c) 2016 Society of Chemical
      Industry.

PMID- 27714917
TI  - Personality traits in Huntington's disease: An exploratory study of gene
      expansion carriers and non-carriers.
AB  - Huntington's disease (HD) is associated with risk for developing psychiatric
      symptoms. Vulnerability or resilience to psychiatric symptoms may be associated
      with personality traits. This exploratory study, aimed to investigate personality
      traits in a large cohort of HD carriers and at risk gene-expansion negative
      individuals (HD non-carriers), exploring whether carrying the HD gene or growing
      up in an HD family influences personality traits. Forty-seven HD carriers, Thirty
      nine HD non-carriers, and 121 healthy controls answered the Danish version of the
      revised NEO personality inventory. Comparisons between HD carriers and HD non
      carriers were mostly non-significant but the combined group of HD carriers and
      non-carriers showed significantly higher scores on the facets: "hostility,"
      "assertiveness," and "activity" and on the trait "Conscientiousness" relative to
      controls, "Conscientiousness" have been associated with resilience to psychiatric
      symptoms. Twelve HD carriers and non-carriers were classified as depressed and
      showed significantly lower scores on "Extraversion" and "Conscientiousness" and
      significantly higher scores on "Neuroticism," which are associated with
      vulnerability to psychiatric symptoms. Our findings suggest that, there is no
      direct effect of the HD gene on personality traits, but that personality
      assessment may be relevant to use when identifying individuals from HD families
      who are vulnerable to develop psychiatric symptoms. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27714918
TI  - Setting up your own research group.
AB  - As an early career investigator, starting one's own research group is often the
      next important step towards a tenured academic position. As a clinical
      epidemiologist who has recently moved from Leiden in the Netherlands, where I
      obtained my PhD, to become a group leader in Berlin, Germany, I have been through
      this transition. In the first few months as a group leader, I encountered several
      new situations, as might be expected for any other novice group leader. This
      paper, which describes my own experiences of dealing with these new situations,
      may help other early career researchers in their preparations and efforts to find
      their own approach to handling the new situations typically encountered as a
      group leader.

PMID- 27714920
TI  - Familial Gordon syndrome associated with a PIEZO2 mutation.
AB  - Gordon syndrome or distal arthrogryposis type 3 is a rare autosomal dominant
      disorder characterized by contractures of upper and lower limbs. It is
      distinguishable from other forms of distal arthrogryposis by cleft palate and
      short stature. Recently, Gordon syndrome has been associated to heterozygous
      mutations in the piezo-type mechanosensitive ion channel component 2 gene
      (PIEZO2). Different mutations of this gene also cause distal arthrogryposis type
      5 and Marden-Walker syndrome. Dysfunction of this ion channel provides
      pleiotropic effects on joints, ocular muscles, and bone development. Here, we
      present a family with three affected individuals exhibiting multiple contractures
      (metacarpo-phalangeal and interphalangeal joints as well as elbow, shoulder,
      knee, and ankle joints), clubfeet, short stature, bifid uvula/cleft palate, and a
      distinct facial phenotype including ptosis. In addition, mild intellectual
      disability and delay in psychomotor development are obvious. The
      multigenerational phenotypic spectrum of Gordon syndrome is present in the 37
      year-old father, his 4-year-old son and a male neonate showing typical signs of
      arthrogryposis in the prenatal ultrasound examination already seen at 13 week of
      gestation. In all affected family members, we identified the PIEZO2 mutation
      c.8057G>A (p.Arg2686His) by Sanger sequencing. Our analysis indicated that mild
      delay in psychomotor development and intellectual disability could be part of the
      phenotypic spectrum of Gordon syndrome. (c) 2016 Wiley Periodicals, Inc.

PMID- 27714919
TI  - The association of anti-platelet factor 4/heparin antibodies with early and
      delayed thromboembolism after cardiac surgery.
AB  - : Essentials We evaluated antibody status, thromboembolism and survival after
      cardiac surgery. Positive antibody tests are common - over 50% are seropositive
      at 30 days. Seropositivity did not increase thromboembolism or impair survival
      after cardiac surgery. Results show heparin induced thrombocytopenia antibody
      screening after surgery is not warranted. SUMMARY: Background Heparin-induced
      thrombocytopenia (HIT) is a prothrombotic response to heparin therapy with
      platelet-activating, anti-platelet factor 4 (PF4)/heparin antibodies leading to
      thrombocytopenia associated with thromboembolism. Objective We tested the
      hypothesis that anti-PF4/heparin antibodies are associated with thromboembolism
      after cardiac surgery. Methods This multicenter, prospective cohort study
      collected laboratory and clinical data up to 30 days after surgery and longer
      term clinical follow-up data. The primary outcome variable combined new arterial
      or venous thromboembolic complications (TECs) with all-cause death until 90 days
      after surgery. Laboratory analyses included platelet counts and anti-PF4/heparin
      antibody titers (GTI ELISA), with a confirmatory excess heparin step and
      serotonin release assay. Chi-square testing was used to test the relationship
      between our outcome and HIT antibody seropositivity. Results Initially, 1021
      patients were enrolled between August 2006 and May 2009, and follow-up was
      completed in December 2014. Seropositivity defined by OD > 0.4 was common, being
      almost 20% preoperatively, > 30% by discharge, and > 60% by day 30. Death (1.7%
      within 30 days) or TECs (69 in total) were more likely if the partient was
      seronegative (OD < 0.4), but positivity defined by OD > 1.0 or including an
      excess heparin confirmatory step resulted in equal incidence of death or TECs,
      whether the patient was seronegative or seropositive. Incorporating the serotonin
      release assay for platelet-activating antibodies did not alter these findings.
      Conclusions Seropositivity for anti-PF4/heparin antibodies does not increase the
      risk of death or thromboembolism after cardiac surgery. Screening is not
      indicated, and seropositivity should only be interpreted in the context of
      clinical evidence for HIT. TRIAL REGISTRATION: Duke IRB Protocol #00010736.

PMID- 27714921
TI  - A Counterion-Directed Approach to the Diels-Alder Paradigm: Cascade Synthesis of
      Tricyclic Fused Cyclopropanes.
AB  - An approach to the intramolecular Diels-Alder reaction has led to a cascade
      synthesis of complex carbocycles composed of three fused rings and up to five
      stereocenters with complete stereocontrol. Computational analysis reveals that
      the reaction proceeds by a Michael/Michael/cyclopropanation/epimerization cascade
      in which size and coordination of the counterion is key.

PMID- 27714922
TI  - Triterpenoids-Enriched Extract from the Aerial Parts of Salvia miltiorrhiza
      Regulates Macrophage Polarization and Ameliorates Insulin Resistance in High-Fat
      Fed Mice.
AB  - Adipose tissue inflammation and macrophage polarization are tightly associated
      with the development of obesity-associated insulin resistance. Our previous
      studies have demonstrated the triterpenoids-enriched extract from the aerial
      parts of Salvia miltiorrhiza (TTE) could significantly improve atherosclerosis in
      LDLR-/- mice. However, its molecular mechanisms of TTE ameliorating insulin
      resistance remain unclear. In the present study, obesity model with insulin
      resistance induced by feeding high-fat diet (HFD) was established. Dietary TTE
      attenuated hyperlipidemia, improved glucose intolerance in mice and mediated the
      activation of IRS-1/PI3K/Akt insulin signaling pathway. Meanwhile, dietary TTE
      also attenuated macrophage infiltrations into adipose tissue and modified the
      phenotype ratio of M1/M2 macrophages. Furthermore, our results showed that TTE
      regulated the polarization of macrophages partly via adenosine monophosphate
      activated kinase (AMPK). Taken together, these findings suggested that TTE has a
      potential clinical utility in improving insulin resistance. Its mechanisms might
      be contributed to its beneficial effects on macrophage polarization via AMPK.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27714923
TI  - The evolution of the avian bill as a thermoregulatory organ.
AB  - The avian bill is a textbook example of how evolution shapes morphology in
      response to changing environments. Bills of seed-specialist finches in particular
      have been the focus of intense study demonstrating how climatic fluctuations
      acting on food availability drive bill size and shape. The avian bill also plays
      an important but under-appreciated role in body temperature regulation, and
      therefore in energetics. Birds are endothermic and rely on numerous mechanisms
      for balancing internal heat production with biophysical constraints of the
      environment. The bill is highly vascularised and heat exchange with the
      environment can vary substantially, ranging from around 2% to as high as 400% of
      basal heat production in certain species. This heat exchange may impact how birds
      respond to heat stress, substitute for evaporative water loss at elevated
      temperatures or environments of altered water availability, or be an energetic
      liability at low environmental temperatures. As a result, in numerous taxa, there
      is evidence for a positive association between bill size and environmental
      temperatures, both within and among species. Therefore, bill size is both
      developmentally flexible and evolutionarily adaptive in response to temperature.
      Understanding the evolution of variation in bill size however, requires
      explanations of all potential mechanisms. The purpose of this review, therefore,
      is to promote a greater understanding of the role of temperature on shaping bill
      size over spatial gradients as well as developmental, seasonal, and evolutionary
      timescales.

PMID- 27714924
TI  - Ionic Liquids and Poly(ionic liquid)s for Morphosynthesis of Inorganic Materials.
AB  - Ionic liquids (ILs) are new, innovative ionic solvents with rich physicochemical
      properties and intriguing pre-organized solvent structures; these materials offer
      great potential to impact across versatile areas of scientific research, for
      example, synthetic inorganic chemistry. Recent use of ILs as precursors,
      templates, and solvents has led to inorganic materials with tailored sizes,
      dimensionalities, morphologies, and functionalities that are difficult to obtain,
      or even not accessible, by using conventional solvents. Poly(ionic liquid)s
      (PILs) polymerized from IL monomers also raise the prospect of modifying
      nucleation, growth, and crystallization of inorganic objects, shedding light on
      the synthesis of a wide range of new materials. Here we survey recent key
      progress in using ILs and PILs in the field of synthetic inorganic chemistry. As
      well as highlighting the unique features of ILs and PILs that enable advanced
      synthesis, the effects of adding other solvents to the final products, along with
      the emerging applications of the created inorganic materials will be discussed.
      We finally provide an outlook on several development opportunities that could
      lead to new advancements of this exciting research field.

PMID- 27714925
TI  - Diagnostic reference levels for digital mammography in New South Wales.
AB  - INTRODUCTION: This work aims to explore radiation doses delivered in screening
      mammography in Australia, with a focus on whether compressed breast thickness
      should be used as a guide when determining patient derived diagnostic reference
      levels (DRLs). METHODS: Anonymized mammograms (52,405) were retrieved from a
      central database, and DICOM headers were extracted using third party software.
      Women with breast implants, breast thicknesses outside 20-110 mm and images with
      incomplete exposure or quality assurance (QA) data were excluded. Exposure and QA
      information were utilized to calculate the mean glandular dose (MGD) for 45,054
      mammograms from 61 units representing four manufacturers using previously well
      established methods. The 75th and 95th percentiles were calculated across median
      image MGDs obtained for all included data and according to specific compressed
      breast thickness ranges. RESULTS: The overall median image MGD, minimum, maximum
      were: 1.39, 0.19 and 10.00 mGy, respectively, the 75th and 95th percentiles
      across all units' median image MGD for 60 +/- 5 mm compressed breast thickness
      were 2.06 and 2.69 mGy respectively. Median MGDs, minimum, maximum, 75th and 95th
      percentiles were presented for nine compressed breast thickness ranges, DRLs for
      NSW are suggested for the compressed breast thickness range of 60 +/- 5 mm for
      the whole study and three detector technologies CR, DR, and photon counting to be
      2.06, 2.22, 2.04 and 0.79 mGy respectively. CONCLUSION: MGD is dependent upon
      compressed breast thickness and it is recommended that DRL values should be
      specific to compressed breast thickness and image detector technology.

PMID- 27714926
TI  - Purification of PEDOT:PSS by Ultrafiltration for Highly Conductive Transparent
      Electrode of All-Printed Organic Devices.
AB  - A highly conductive, air stable and scalable poly(3,4-ethylenedioxythiophene)
      (PEDOT): poly(4-styrenesulfonate) (PEDOT:PSS) are prepared by using mass
      production ultrafiltration. By effectively removing excess PSS and various
      reaction impurities using repeated 100 nm pore membrane filtration, purified
      PEDOT:PSS exhibit conductivity as high as 2000 S cm-1 .

PMID- 27714927
TI  - Differences in the emotional and practical experiences of exclusively
      breastfeeding and combination feeding mothers.
AB  - The majority of research examining the barriers to breastfeeding focuses on the
      physical challenges faced by mothers rather than the risks of encountering
      negative emotional and practical feeding experiences. We aimed to quantify the
      emotional and practical experiences of the overall sample of breastfeeding
      mothers and identify the differences in the emotional and practical experiences
      of exclusively breastfeeding mothers and combination feeding mothers, by feeding
      type and intention. Eight hundred forty-five mothers with infants up to 26 weeks
      of age and who had initiated breastfeeding were recruited through relevant social
      media via advertisements providing a link to an online survey. Predictors of
      emotional experiences included guilt, stigma, satisfaction with feeding method,
      and the need to defend themselves due to infant feeding choices. Practical
      predictors included perceived support from health professionals, main sources of
      infant feeding information, and respect from their everyday environment,
      workplace, and when breastfeeding in public. Current feeding type and prenatal
      feeding intention. In the overall sample, 15% of the mothers reported feeling
      guilty, 38% stigmatized, and 55% felt the need to defend their feeding choice.
      Binary logit models revealed that guilt and dissatisfaction were directly
      associated with feeding type, being higher when supplementing with formula. No
      associations with feeding intention were identified. This study demonstrates a
      link between current breastfeeding promotion strategies and the emotional state
      of breastfeeding mothers who supplement with formula to any extent. To minimize
      the negative impact on maternal well-being, it is important that future
      recommendations recognize the challenges that exclusive breastfeeding brings and
      provide a more balanced and realistic target for mothers.

PMID- 27714928
TI  - Bilberry: Chemical Profiling, in Vitro and in Vivo Antioxidant Activity and
      Nephroprotective Effect against Gentamicin Toxicity in Rats.
AB  - We assessed possible protective effect of bilberry diet in rat model of
      nephrotoxicity. In vivo and in vitro antioxidant activity and chemical profiling
      of this functional food was performed. With aid of HPLC-DAD and
      spectrophotometric method, 15 individual anthocyanins were quantified alongside
      total tannin, phenylpropanoid, and anthocyanin content. The study was conducted
      on four groups of rats: control, treated with only gentamicin, treated with only
      bilberry, and treated with both gentamicin and bilberry. Kidney function was
      evaluated by tracking urea and creatinine. Morphology of renal tissue and its
      changes were recorded pathohistologically and quantified morphometrically.
      Bilberry (100 mg/kg daily) showed strong nephroprotective effect against
      gentamicin toxicity in rats (as shown through MDA, AOPP, and catalase levels). In
      conclusion, the demonstrated protective activity of bilberry extract matched well
      with the assessed in vivo and in vitro antioxidant activity as well as with its
      polyphenolic content, particularly with high anthocyanin levels. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27714929
TI  - Vitamin D modulation of innate immune responses to respiratory viral infections.
AB  - Vitamin D, in addition to its classical functions in bone homeostasis, has a
      modulatory and regulatory role in multiple processes, including host defense,
      inflammation, immunity, and epithelial repair. Patients with respiratory disease
      are frequently deficient in vitamin D, implying that supplementation might
      provide significant benefit to these patients. Respiratory viral infections are
      common and are the main trigger of acute exacerbations and hospitalization in
      children and adults with asthma and other airways diseases. Respiratory
      monocytes/macrophages and epithelial cells constitutively express the vitamin D
      receptor. Vitamin D, acting through this receptor, may be important in protection
      against respiratory infections. Whether the in vitro findings can be translated
      into a substantial in vivo benefit still remains uncertain. Here we review the in
      vitro data on the role of vitamin D in antiviral innate immunity, the data
      concerning the deficient levels of vitamin D in lung diseases, and the in vivo
      role of supplementation as protection against respiratory viral infections in
      healthy individuals and in patients with chronic respiratory diseases. Finally,
      we suggest ways of improving the effectiveness of vitamin D as an adjuvant in the
      prevention and treatment of acute respiratory infections.

PMID- 27714930
TI  - Holographic Structuring of Elastomer Actuator: First True Monolithic Tunable
      Elastomer Optics.
AB  - Volume diffraction gratings (VDGs) are inscribed selectively by diffusive
      introduction of benzophenone and subsequent UV-holographic structuring into an
      electroactive dielectric elastomer actuator (DEA), to afford a continuous voltage
      controlled grating shift of 17%. The internal stress coupling of DEA and optical
      domain allows for a new generation of true monolithic tunable elastomer optics
      with voltage controlled properties.

PMID- 27714931
TI  - Synthesis of honokiol analogues and evaluation of their modulating action on VEGF
      protein secretion and telomerase-related gene expressions.
AB  - A group of 36 biphenyl derivatives structurally related to honokiol were
      synthesized by means of Suzuki coupling reactions. Their cytotoxicities were
      evaluated and compared to that of honokiol. Some of the compounds were then
      evaluated for their ability to downregulate the secretion of the VEGF protein and
      the expression of the VEGF, hTERT, and c-Myc genes; the two latter involved in
      the activation of telomerase in tumoral cells. Some of the synthetized
      derivatives showed promising pharmacological features as they exhibited IC50
      values in low micromolar range, good therapeutic margins, and a multiple mode of
      action on tumor cells based on the inhibition of VEGF and, at the same time, of
      the expression of genes related to the activation of telomerase.

PMID- 27714932
TI  - MediLex: the medical jargon-busting game.
AB  - BACKGROUND: During their training, medical students are expected to acquire the
      ability to use thousands of new terms that make up the medical lexicon. Clear
      communication requires knowledge of this lexicon. We developed a simple word
      game, MediLex, to facilitate the development of these skills. This paper
      describes the intervention and evaluates students' experiences. METHODS: MediLex
      is a card-based description game played in small groups. One hundred cards
      contain 500 medical terms grouped into five categories. The cardholder is asked
      to describe the terms on the card while group members have a limited time to
      deduce the term being described. Students were asked to evaluate MediLex using an
      electronic survey with free-text responses. Content analysis was undertaken by
      two independent researchers, and after discussion a consensus on themes was
      reached. Medical students are expected to acquire the ability to use thousands of
      new terms that make up the medical lexicon RESULTS: MediLex was used on six
      different occasions. Sixty-eight students played the game and 61 completed the
      survey. Fifty-six out of 61 students deemed MediLex to be a valuable learning
      experience. The analysis of responses revealed five themes: 'highlighted
      knowledge gaps'; 'revision/reactivation of knowledge'; 'explanation skills';
      'fun/engaging'; and 'fast pace'. DISCUSSION: Learning new vocabulary is a complex
      process, yet is a principle contributor to comprehension, fluency and
      achievement. Research suggests that playing games with content vocabulary allows
      learners to explore pronunciation and meanings simultaneously. MediLex allows
      learners to do this, whilst giving the opportunity to hear their peers'
      comprehension of meaning. Mastering the medical lexicon is a huge challenge
      because of the breadth and complexity of medical terminology, and focused
      teaching on this appears to be well received by students.

PMID- 27714933
TI  - Structural damage of Bacillus subtilis biofilms using pulsed laser interaction
      with gold thin films.
AB  - There is a huge interest in developing strategies to effectively eliminate
      biofilms due to their negative impact in both industrial and clinical settings.
      In this study, structural damage was induced on two day-old B. subtilis biofilms
      using the interaction of 532 nm pulsed laser with gold thin films. Radiant
      exposure of 225 mJ/cm2 induced distinct changes on the surface structure and
      overall morphology of the matured biofilms after laser irradiation. Moreover, at
      the radiant exposure used, changes in the colour and viscosity of the biofilm
      were observed which may indicate a compromised extracellular matrix. Irradiated
      biofilms in the presence of gold film also showed strong propidium iodide signal
      which implies an increase in the number of dead bacterial cells after laser
      treatment. Thus, this laser-based technique is a promising approach in targeting
      and eradicating matured biofilms attached on surfaces such as medical implants.

PMID- 27714934
TI  - Organofluorine Isoselenocyanate Analogues of Sulforaphane: Synthesis and
      Anticancer Activity.
AB  - A series of previously unknown sulforaphane analogues with organofluorine
      substituents bonded to the sulfinyl sulfur atom, an isoselenocyanate moiety in
      place of the isothiocyanate group, the central sulfur atom in various oxidation
      states, and different numbers of methylene groups in the central alkyl chain were
      synthesized and fully characterized. All new compounds were tested for their
      biological properties in vitro and demonstrated much higher anticancer activity
      against two breast cancer cell lines than that shown by native sulforaphane; at
      the same time, the compounds were less toxic for normal cells. The influence of
      the particular structural changes in the molecules on the cytotoxicity is
      discussed.

PMID- 27714935
TI  - Is Reading Impairment Associated with Enhanced Holistic Processing in Comparative
      Visual Search?
AB  - This study explores a proposition that individuals with dyslexia develop enhanced
      peripheral vision to process visual-spatial information holistically.
      Participants included 18 individuals diagnosed with dyslexia and 18 who were not.
      The experiment used a comparative visual search design consisting of two blocks
      of 72 trials. Each trial presented two halves of the display each comprising
      three kinds of shapes in three colours to be compared side-by-side. Participants
      performed a conjunctive search to ascertain whether the two halves were
      identical. In the first block, participants were provided no instruction
      regarding the visual-spatial processing strategy they were to employ. In the
      second block, participants were instructed to use a holistic processing strategy
      to defocus their attention and perform the comparison by examining the whole
      screen at once. The results did not support the hypothesis associating dyslexia
      with talents for holistic visual processing. Using holistic processing strategy,
      both groups scored lower in accuracy and reacted faster, compared to the first
      block. Impaired readers consistently reacted more slowly and did not exhibit
      enhanced accuracy. Given the extant evidence of strengths for holistic visual
      processing in impaired readers, these findings are important because they suggest
      such strengths may be task dependent. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27714936
TI  - Detection of stanozolol O- and N-sulfate metabolites and their evaluation as
      additional markers in doping control.
AB  - Stanozolol (STAN) is one of the most frequently detected anabolic androgenic
      steroids in sports drug testing. STAN misuse is commonly detected by monitoring
      metabolites excreted conjugated with glucuronic acid after enzymatic hydrolysis
      or using direct detection by liquid chromatography-tandem mass spectrometry (LC
      MS/MS). It is well known that some of the previously described metabolites are
      the result of the formation of sulfate conjugates in C17, which are converted to
      their 17-epimers in urine. Therefore, sulfation is an important phase II
      metabolic pathway of STAN that has not been comprehensively studied. The aim of
      this work was to evaluate the sulfate fraction of STAN metabolism by LC-MS/MS to
      establish potential long-term metabolites valuable for doping control purposes.
      STAN was administered to six healthy male volunteers involving oral or
      intramuscular administration and urine samples were collected up to 31 days after
      administration. Sulfation of the phase I metabolites commercially available as
      standards was performed in order to obtain MS data useful to develop analytical
      strategies (neutral loss scan, precursor ion scan and selected reaction
      monitoring acquisitions modes) to detect potential sulfate metabolites. Eleven
      sulfate metabolites (M-I to M-XI) were detected and characterized by LC-MS/MS.
      This paper provides valuable data on the ionization and fragmentation of O
      sulfates and N-sulfates. For STAN, results showed that sulfates do not improve
      the retrospectivity of the detection compared to the previously described long
      term metabolite (epistanozolol-N-glucuronide). However, sulfate metabolites could
      be additional markers for the detection of STAN misuse. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27714937
TI  - PlasmoSEP: Predicting surface-exposed proteins on the malaria parasite using
      semisupervised self-training and expert-annotated data.
AB  - Accurate and comprehensive identification of surface-exposed proteins (SEPs) in
      parasites is a key step in developing novel subunit vaccines. However, the
      reliability of MS-based high-throughput methods for proteome-wide mapping of SEPs
      continues to be limited due to high rates of false positives (i.e., proteins
      mistakenly identified as surface exposed) as well as false negatives (i.e., SEPs
      not detected due to low expression or other technical limitations). We propose a
      framework called PlasmoSEP for the reliable identification of SEPs using a novel
      semisupervised learning algorithm that combines SEPs identified by high
      throughput experiments and expert annotation of high-throughput data to augment
      labeled data for training a predictive model. Our experiments using high
      throughput data from the Plasmodium falciparum surface-exposed proteome provide
      several novel high-confidence predictions of SEPs in P. falciparum and also
      confirm expert annotations for several others. Furthermore, PlasmoSEP predicts
      that 25 of 37 experimentally identified SEPs in Plasmodium yoelii salivary gland
      sporozoites are likely to be SEPs. Finally, PlasmoSEP predicts several novel SEPs
      in P. yoelii and Plasmodium vivax malaria parasites that can be validated for
      further vaccine studies. Our computational framework can be easily adapted to
      improve the interpretation of data from high-throughput studies.

PMID- 27714938
TI  - A case of giant cell-rich solitary fibrous tumor in the external auditory canal.
AB  - We present a rare case of giant cell-rich solitary fibrous tumor (SFT) arising at
      the left external auditory canal in a 31-year-old woman. The tumor was well
      circumscribed and composed of spindle-shaped cells with abundant collagenous
      bands. Scattered multinucleate giant cells were observed, some of which lined
      pseudovascular spaces. Although a focal mild-hypercellular area was observed,
      mitoses were rare and necrosis was absent. Interstitial mast cells were
      scattered, especially in the hypercellular area. Immunohistochemically, CD34,
      vimentin, and Bcl-2 presented diffuse positivity. Moreover, both mononuclear
      spindle cells and multinucleate cells showed nuclear STAT6 positivity, while NAB2
      STAT6 fusion gene could not be detected by reverse transcription polymerase chain
      reaction using formalin-fixed specimen. These findings suggest the pathological
      diagnosis of giant cell-rich SFT, previously known as giant cell angiofibroma,
      which is a rare variant of SFT with multinucleate giant cells and occurs
      predominantly in orbital region. Although giant cell-rich SFTs of extra-orbital
      sites have been reported, to our knowledge, this is the first case arising in the
      external auditory canal. Giant cell-rich SFT should be considered as a
      differential diagnosis of spindle cell lesion with multinucleate giant cells, and
      STAT6 immunohistochemistry should be performed to distinguish this rare tumor
      from other mesenchymal neoplasms.

PMID- 27714940
TI  - Spotlights on our sister journals: Chem. Eur. J. 43/2016.

PMID- 27714939
TI  - Tumour-Targeted Drug Delivery with Mannose-Functionalized Nanoparticles Self
      Assembled from Amphiphilic beta-Cyclodextrins.
AB  - Multivalent mannose-functionalized nanoparticles self-assembled from amphiphilic
      beta-cyclodextrins (beta-CDs) facilitate the targeted delivery of anticancer
      drugs to specific cancer cells. Doxorubicin (DOX)-loaded nanoparticles equipped
      with multivalent mannose target units were efficiently taken up via receptor
      mediated endocytosis by MDA-MB-231 breast cancer cells that overexpress the
      mannose receptor. Upon entering the cell, the intracellular pH causes the release
      of DOX, which triggers apoptosis. Targeting by multivalent mannose significantly
      improved the capability of DOX-loaded nanoparticles to inhibit the growth of MDA
      MB-231 cancer cells with minimal side effects in vivo. This targeted and
      controlled drug delivery system holds promise as a nanotherapeutic for cancer
      treatment.

PMID- 27714941
TI  - Bevacizumab for non-small-cell lung cancer: A nested case control study of risk
      factors for hemoptysis.
AB  - Potentially life-threatening, serious hemoptysis is an adverse event associated
      with bevacizumab in non-squamous non-small-cell lung cancer (NSCLC) trials.
      Suggested risk factors include central tumor location and cavitation; however,
      the profile of hemoptysis occurrence in clinical practice is still unclear. A
      nested case-control study was conducted to assess the onset profile and risk
      factors for hemoptysis in bevacizumab-treated patients in a real-world setting in
      Japan. After bevacizumab was approved for NSCLC, physicians registered all NSCLC
      patients scheduled for bevacizumab therapy, from November 2009 to August 2011.
      Patients developing grade 2 hemoptysis requiring an injectable hemostatic agent
      or grade >=3 hemoptysis were selected as case subjects, matched with four control
      subjects each. Case report forms were collected after an observation period of 24
      weeks. Radiologists assessed blinded thoracic images. Risk factors for hemoptysis
      were assessed by univariate and stepwise multivariate analysis. Of 6774 patients
      registered, 23 (0.3%) experienced grade >=2 drug-related hemoptysis. A total of
      104 patients (21 cases, 83 controls) were analyzed by central reviewers for risk
      factors of hemoptysis occurrence. In the univariate analysis seven factors were
      associated with hemoptysis. In the step-wise multivariate analysis, prior
      thoracic radiotherapy (P = 0.1844), presence of tumor exposure in the central
      airway (P = 0.0256) and concomitant radiotherapy (P = 0.1169) were identified as
      risk factors for hemoptysis. While the incidence of hemoptysis was low in the
      real-world setting in Japan, the three risk factors identified, prior thoracic
      radiotherapy, presence of tumor exposure in the central airway and concomitant
      radiotherapy, should be considered when selecting patients for bevacizumab
      treatment. Although technically classed as a clinical trial, a nested case
      control study was a non-interventional surveillance study analyzing all NSCLC
      patients receiving bevacizumab in Japan, therefore it was not registered as a
      phase II/III clinical trial would be.

PMID- 27714943
TI  - Is HLA-E a possible genetic marker relevant for natural conception?
AB  - BACKGROUND: HLA-E products, class Ib human leukocyte antigens, act in the
      immunology of human reproduction as modulators of the maternal immune system
      during pregnancy. AIMS: To evaluate HLA-E role in the establishment of a viable
      pregnancy. MATERIALS & METHODS: HLA-E was genotyped by sequence-based typing
      (SBT) and analyzed for specific polymorphisms, comparing couples who underwent
      assisted reproduction treatment (ART) and fertile control couples. RESULTS: There
      was a significant difference in HLA-E allele and genotype distributions between
      ART couples and control couples. The allele HLA-E*01:03 was observed in 63.2% of
      ART men and in 35.1% of fertile men (P = 0.0032). CONCLUSION: These results
      suggest that HLA-E allelic variants may play a role in the modulation of immune
      responses in the context of the inability of natural conception and establishment
      of a viable pregnancy.

PMID- 27714942
TI  - Management of atypical squamous cells of undetermined significance or low-grade
      squamous intraepithelial lesions of the uterine cervix with human papilloma virus
      infection among young women aged less than 25 years.
AB  - Current ASCCP guidelines recommend repeat cytology 12 months after HPV-positive
      results in women aged 21-24 years with either atypical squamous cells of
      undetermined significance (ASCUS) or a low-grade squamous intraepithelial lesion
      (LSIL). The purpose of this study was to validate an algorithm in such women with
      ASCUS or LSIL. A multicenter cross-sectional study was carried out at three
      academic hospitals involving 40,847 Korean women who underwent cervical cancer
      screening with cytology and HPV testing with or without subsequent colposcopic
      biopsies between January 2007 and December 2013. Among a total of 3,193 women
      with available histopathology data, 762 women with ASCUS and 758 with LSIL were
      HPV-positive. Among HPV-positive women with ASCUS, 38.5% of women aged 21-24
      years had >=CIN2, compared to 20.8% of women aged 30-65 years and 21.1% of the
      total women. Among HPV-positive women with LSIL, 25.8% aged 21-24 years had
      >=CIN2, compared to 21.2% of women aged 30-65 years and 21.9% of the total women.
      In HPV-positive women with ASCUS/LSIL aged less than 25 years, the prevalence of
      >=CIN2 lesions was 34.5%, which was significantly higher than that (21.0%) in
      women aged >=25 years. The risk of >=CIN2 lesions in HPV-positive Korean women
      aged 21-24 years with ASCUS or LSIL was not lower than that in older women.
      Colposcopic examination should be considered for management of HPV-positive young
      women with ASCUS or LSIL. Diagn. Cytopathol. 2016;44:959-963. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27714944
TI  - Sequence analysis of RAS and RAF mutation hot spots in canine carcinoma.
AB  - Recent discovery of the BRAF V595E mutation in a variety of canine cancers
      indicates that mutant BRAF may represent a novel therapeutic target. Presence of
      RAS mutations is associated with poor tumour response to BRAF inhibition but has
      not been investigated in BRAF-mutated canine cancers. The aim of this study was
      to evaluate the mutational status of three RAS genes (HRAS, KRAS and NRAS) in
      four types of canine carcinoma with and without the BRAF V595E mutation. Novel
      HRAS mutations were identified in 18% (3/17) of oral squamous cell carcinoma,
      whereas 17% (3/18) of pulmonary carcinoma carried KRAS or NRAS mutations. These
      RAS mutations and BRAF V595E were mutually exclusive, indicating similar
      functional consequence of these mutations (e.g. MAPK pathway activation). In
      contrast, RAS mutations were absent in 39 urothelial carcinoma and 19 prostatic
      carcinoma, adding another rational for BRAF-targeted therapy for these canine
      cancers.

PMID- 27714945
TI  - Preferred frequencies and waveforms for spinal cord stimulation in patients with
      complex regional pain syndrome: A multicentre, double-blind, randomized and
      placebo-controlled crossover trial.
AB  - BACKGROUND: Conventional tonic spinal cord stimulation (SCS) is an effective
      treatment for patients with therapy-resistant complex regional pain syndrome
      (CRPS). Although the therapeutic effect of SCS can diminish over time due to
      tolerance, pain control can be regained by changing the pulse width and the
      amplitude and/or by increasing the stimulation frequency. This multicentre,
      double-blind, randomized and placebo-controlled crossover trial was conducted to
      investigate whether more effective pain reduction is achieved with different
      frequencies (trial registration, current controlled trials, ISRCTN 36655259).
      METHODS: The investigated settings are as follows: standard 40, 500, 1200 Hz,
      burst and placebo stimulation. All five were programmed in random order during
      the 10-week crossover period (2 weeks/setting). The primary outcome parameters
      were scores on the visual analogue scale (VAS), McGill Pain Questionnaire (MPQ)
      and the Global Perceived Effect (GPE); at the end of the crossover period,
      patients decided which SCS setting they preferred. A linear mixed models analysis
      was performed in 29 patients who completed the crossover trial. RESULTS:
      Significant pain reduction and GPE satisfaction was achieved with four SCS
      settings compared with placebo stimulation, and these four settings did not
      differ significantly from each other. Standard stimulation was preferred by 48%
      of the patients, while 52% preferred non-standard stimulation. Other than pain
      reduction, factors such as user-friendliness, comfort and recharging time may
      have influenced the patient's final decision for the preferred stimulation
      setting. CONCLUSIONS: Apparently, for various reasons, patients have a preference
      for different SCS setting. Therefore, future neuromodulation should aim to
      implement customized individual patient care by incorporating all stimulation
      options in one device. SIGNIFICANCE: This study demonstrates that standard
      frequency SCS is an effective therapy for patients with CRPS. However, it also
      demonstrates that patients can often gain better pain reduction with non-standard
      frequencies of SCS. Furthermore, it shows that the preferred stimulation setting
      is not solely driven by the amount of pain reduction, but is also influenced by
      which stimulation setting feels most comfortable and provides the best user
      friendliness. Therefore, we strive to maximize the therapeutic effects of SCS in
      as many patients as possible. This can be achieved with customized individual
      patient care by incorporating the various frequencies and waveforms into one
      single device.

PMID- 27714946
TI  - Access to Acyclic Z-Enediynes by Alkyne Trimerization: Cooperative Bimetallic
      Catalysis Using Air as the Oxidant.
AB  - Presented herein is a mild, operationally simple, mix-and-go procedure for the
      synthesis of acyclic trisubstituted Z-enediynes, from readily available terminal
      alkynes, in good yields. This method stems from a serendipitous discovery, and
      makes use of cooperative palladium/copper bimetallic catalysis and air as an
      oxidant to effect an intriguing alkyne trimerization to yield the valuable Z
      enediyne moiety.

PMID- 27714947
TI  - Corrigendum.

PMID- 27714948
TI  - External scrutiny, faculty research culture and the changing university.

PMID- 27714950
TI  - Low-power laser irradiation in salivary glands reduces glycemia in streptozotocin
      induced diabetic female rats.
AB  - Low-power laser irradiation (LPLI) has been extensively employed to modulate
      inflammation in vitro and in vivo. Previous reports from our group indicated that
      LPLI might regulate glycemia in diabetic animals. Diabetes results in chronic
      hyperglycemia and therefore chronic inflammation by upregulation of inflammatory
      markers such as the high mobility group box 1 (HMGB1) protein. Thus this study
      aimed to analyze the LPLI effects upon blood glucose levels, plasma insulin and
      HMGB1 concentrations in a diabetes experimental rat model. Streptozotocin-induced
      diabetic rats were irradiated in the salivary glands area with a diode laser
      applied at 660 nm, 70 mW, 20 J/cm2 , 22.4 J, with a spot area of 0.028 cm2 and
      its effects were evaluated. LPLI significantly reduced diabetic rat
      hyperglycemia, without changing insulin or HMGB1 plasma levels, but possibly by
      ameliorating the insulin resistance in these animals. These findings suggest that
      LPLI might have a systemic effect, but more studies are necessary to better
      understand its mechanisms. Fasting blood glucose measured by peroxidase-glucose
      oxidase (PGO) method (A), showing a reduction of diabetic animals glycemia after
      LPLI. LPLI probably reduced the hyperglycemia in diabetes by improving the
      insulin resistance in these animals (B). C n = 10, CL n = 10, D n = 7 and DL n =
      8. Data are expressed as mean +/- SD; * P < 0.05 vs. respective control group; #
      P < 0.05 vs. D group.

PMID- 27714951
TI  - Insecticide resistance, control failure likelihood and the First Law of
      Geography.
AB  - Insecticide resistance is a broadly recognized ecological backlash resulting from
      insecticide use and is widely reported among arthropod pest species with well
      recognized underlying mechanisms and consequences. Nonetheless, insecticide
      resistance is the subject of evolving conceptual views that introduces a
      different concept useful if recognized in its own right - the risk or likelihood
      of control failure. Here we suggest an experimental approach to assess the
      likelihood of control failure of an insecticide allowing for consistent decision
      making regarding management of insecticide resistance. We also challenge the
      current emphasis on limited spatial sampling of arthropod populations for
      resistance diagnosis in favor of comprehensive spatial sampling. This necessarily
      requires larger population sampling - aiming to use spatial analysis in area-wide
      surveys - to recognize focal points of insecticide resistance and/or control
      failure that will better direct management efforts. The continuous geographical
      scale of such surveys will depend on the arthropod pest species, the pattern of
      insecticide use and many other potential factors. Regardless, distance dependence
      among sampling sites should still hold, following the maxim that the closer two
      things are, the more they resemble each other, which is the basis of Tobler's
      First Law of Geography. (c) 2016 Society of Chemical Industry.

PMID- 27714952
TI  - Detection of 5alpha-androst-2-en-17-one and variants: Identification of main
      urinary metabolites in human urine samples by GC-MS and NMR.
AB  - Two steroids were identified in a supplement named D-2 following the detection of
      unknown compounds during the routine testing of an athlete's sample. The main
      glucuroconjugated metabolites were isolated from this urine by high performance
      liquid chromatography (HPLC) following enzymatic hydrolysis and identified by gas
      chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR)
      analyses as being 2alpha-hydroxy-5alpha-androst-3-en-17-one (M1) and 2beta,3alpha
      dihydroxy-5alpha-androstan-17-one (M2). A third metabolite, 3alpha,4beta
      dihydroxy-5alpha-androstan-17-one (M3) was also detected, however in lower
      amounts. The precursor steroids, 5alpha-androst-2-en-17-one (1) and 5alpha
      androst-3-en-17-one (2) were present in the first D-2 products offered on the
      Internet. Later, the corresponding 17-hydroxyl compounds were offered as such or
      as esters (acetate, cypionate) in different relative ratios. Both M2 and M3 were
      synthesized from the trans-diaxial hydrolysis of the corresponding 2alpha,3alpha-
      and 3alpha,4alpha-epoxides (3). These were excreted in the hours following the
      controlled administration of the commercial product called D-2 R to a male
      volunteer and were also produced from the incubation of 1 and 2 with S9 liver
      fractions. Some preparations contain predominantly the alkene in C-2 and,
      therefore, an efficient detection method must include both primary metabolites M1
      and M2. The latter was found equally in the fractions extracted following the
      enzymatic hydrolysis with beta-glucuronidase and the chemical solvolysis, which
      may ease its identification. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27714953
TI  - Usefulness of assisted procedures for arteriovenous fistula maturation without
      compromising access patency.
AB  - INTRODUCTION: To increase the rate of arteriovenous fistula (AVF) use, assisted
      procedures for immature AVF have been strenuously performed. However, this is
      controversial in that an AVF matured by these assisted procedures may require
      more frequent intervention to maintain its patency, and have decreased long-term
      patency. METHODS: Eighty four AVFs that were matured with assisted maturation
      procedures and 266 AVFs that matured spontaneously without intervention, created
      between November 2009 and March 2013 from the hemodialysis (HD) vascular access
      (VA) cohort, were compared retrospectively and we also investigated the factors
      that may influence AVF long-term patency. Median follow-up was 26.8 months
      (interquartile range, 6.6-45.0 months). FINDINGS: Access survival did not differ
      between AVFs matured by assisted procedures and spontaneously mature AVFs (P =
      0.29). In multivariate Cox regression analysis of AVF survival, age (HR, 1.029;
      95% CI, 1.004-1.056; P = 0.024), maturation without assisted procedures 4-6 weeks
      after AVF creation (HR, 0.233; 95% CI, 0.107-0.506; P < 0.001), and AVF
      thrombosis (HR, 26.511; 95% CI, 10.986-63.978; P < 0.001) were significantly
      associated with AVF survival. Performance of assisted procedures to induce AVF
      maturation did not influence AVF survival (HR, 0.437; 95% CI, 0.191-1.002; P =
      0.05). DISCUSSION: Our results support that idea that assisted maturation
      procedures can ensure the success of immature AVF without compromising long-term
      patency. These procedures can be considered more positively for increasing AVF
      use for VA placement in HD patients.

PMID- 27714954
TI  - Nursing with care: a meditation in three voices (in memoriam John S. Drummond).
AB  - This paper is a written version of a talk given at the 19th International
      Philosophy of Nursing conference to honour the contributions of Dr. John S.
      Drummond, nurse and philosopher, to an ongoing and collective project we could
      call 'thinking nursing'. Over the course of his career, John Drummond published a
      series of essays, building on his reading of the works of continental
      philosophers such as Nietzsche, Lyotard or Deleuze, that draw us to nursing as a
      matter of concern, and that through their incisive analyses, help us to pay
      attention to the changes that are going on with nursing now. Though this essay
      began as a way to mark the death of John Drummond, and to pay tribute to his
      work, we also find that our return to his texts is like other experiences of
      return - the pleasure of experiencing something anew, as if for the first time.

PMID- 27714955
TI  - Restricting dietary sodium reduces plasma sodium response to exercise in the
      heat.
AB  - Exercise-associated hyponatremia can be life-threatening. Excessive hypotonic
      fluid ingestion is the primary etiological factor but does not explain all
      variability. Possible effects of chronic sodium intake are unknown. The aim of
      this study was to determine whether dietary sodium affects plasma sodium
      concentration [Na+ ] during exercise in the heat, when water intake nearly
      matches mass loss. Endurance-trained men (n = 9) participated in this crossover
      experiment. Each followed a low-sodium (lowNa) or high-sodium (highNa) diet for 9
      days with 24-h fluid intakes and urine outputs measured before experimental
      trials (day 10). The trials were >=2 week apart. Trials comprised 3 h (or if not
      possible to complete, to exhaustion) cycling (55% VO2max ; 34  degrees C, 65% RH)
      with water intake approximating mass loss. Plasma [Na+ ], hematocrit, sweat and
      urine [Na+ ], heart rate, core temperature, and subjective perceptions were
      monitored. Urine [Na+ ] was lower on lowNa 24 h prior to (31 +/- 24, 76 +/- 30
      mmol/L, P = 0.027) and during trials (10 +/- 10, 52 +/- 32 mmol/L, P = 0.004).
      Body mass was lower on lowNa (79.6 +/- 8.5, 80.5 +/- 8.9, P = 0.03). Plasma [Na+
      ] was lower on lowNa before (137 +/- 2, 140 +/- 3, P = 0.007) and throughout
      exercise (P = 0.001). Sweat [Na+ ] was unaffected by diet (54.5 +/- 40, 54.5 +/-
      23 mmol/L, P = 0.99). Heart rate and core temperature were higher on lowNa (P <=
      0.001). Despite decreased urinary sodium losses, plasma sodium was lower on
      lowNa, with decreased mass indicating (extracellular) water may have been less,
      explaining greater heart rate and core temperature. General population health
      recommendations to lower salt intake may not be appropriate for endurance
      athletes, particularly those training in the heat.

PMID- 27714957
TI  - Discovery of selective protein arginine methyltransferase 5 inhibitors and
      biological evaluations.
AB  - Protein arginine methyltransferase 5 (PRMT5) is an important protein arginine
      methyltransferase that catalyzes the symmetric dimethylation of arginine resides
      on histones or non-histone substrate proteins. It has been thought as a promising
      target for many diseases, particularly cancer. Despite the potential applications
      of PRMT5 inhibitors in cancer treatment, very few of PRMT5i have been publicly
      reported. In this investigation, virtual screening and structure-activity
      relationship studies were carried out to discover novel PRMT5i, which finally led
      to the identification of a number of new PRMT5i. The most active compound, P5i-6,
      exhibited a considerable inhibitory potency against PRMT5 with an IC50 value of
      0.57 MUm, and a high selectivity for PRMT5 against other tested PRMTs. It
      displayed a very good antiviability activity against two colorectal cancer cell
      lines, HT-29 and DLD-1, and one hepatic cancer cell line, HepG2, in a sensitivity
      assay against 36 different cancer cell lines. Western blot assays indicated that
      P5i-6 selectively inhibited the symmetric dimethylations of H4R3 and H3R8 in DLD
      1 cells. Overall, P5i-6 could be used as a chemical probe to investigate new
      functions of PRMT5 in biology and also served as a good lead compound for the
      development of new PRMT5-targeting therapeutic agents.

PMID- 27714958
TI  - Prenatal anemia control and anemia in children aged 6-23 months in sub-Saharan
      Africa.
AB  - It is unclear whether routine prenatal anemia control interventions can reduce
      anemia risk in young children. This study examines the associations between
      prenatal iron supplementation and/or deworming and anemia in children aged 6-23
      months in sub-Saharan Africa (SSA). We analyzed data from Demographic and Health
      Surveys conducted between 2003 and 2014 in 25 SSA countries. The surveys
      collected data on prenatal iron supplementation and deworming and determined
      children's hemoglobin levels through blood testing. We assessed the associations
      between prenatal iron supplementation and/or deworming and anemia using
      multinomial logistic regression. The study included 31,815 mother-child pairs:
      25.0%, 41.4%, and 4.8% of children had mild, moderate, and severe anemia,
      respectively. Compared with children whose mothers did not take iron and
      deworming drugs prenatally, the risk of moderate/severe anemia was reduced among
      children whose mothers took only iron supplements for >=6 months (odds ratio
      [OR]: 0.58; 95% confidence interval [CI]: 0.45-0.76); only deworming drugs (OR:
      0.73; 95% CI: 0.56-0.93); deworming drugs plus iron for <6 months (OR: 0.79; 95%
      CI: 0.67-0.93); and deworming drugs plus iron for >=6 months (OR: 0.77; 95% CI:
      0.59-0.99). Prenatal use of only iron for <6 months was not associated with
      moderate/severe anemia. Prenatal iron and/or deworming drugs had no effect on
      mild anemia. Prenatal anemia control interventions are associated with reduced
      risk of moderate/severe anemia but not with mild anemia in young children in SSA.
      Iron supplements should be taken for >=6 months or with deworming drugs
      prenatally to reduce moderate/severe anemia risk in children.

PMID- 27714959
TI  - Doctors with dyslexia: strategies and support.
AB  - BACKGROUND: Looking beyond dyslexia as an individual doctor's issue requires
      adjusting a working environment to better serve the needs of doctors with
      dyslexia. With an increasing number of doctors disclosing dyslexia at medical
      school, how can educators best provide this support? Our research looks at the
      impact of dyslexia on clinical practice and the coping strategies used by doctors
      to minimise the effect. METHODS: Qualitative data were collected from 14 doctors
      with dyslexia using semi-structured interviews and by survey. 'In situ'
      demonstration interviews were conducted in order to understand how dyslexia is
      managed in the workplace from first-hand experience. Employers and educators who
      have responsibility for meeting the needs of this group were also consulted.
      RESULTS: Even in cases of doctors who had a diagnosis, they often did not
      disclose their dyslexia to their employer. Study participants reported having
      developed individual ways of coping and devised useful 'workarounds'. Support
      from employers comes in the form of 'reasonable adjustments', although from our
      data we cannot be sure that such adjustments contribute to an 'enabling' work
      environment. Supportive characteristics included the opportunity to shadow others
      and the time and space to complete paperwork on a busy ward. How can educators
      best provide support [for doctors with dyslexia]? DISCUSSION: Doctors with
      dyslexia need to be helped to feel comfortable enough to disclose. Educators need
      to challenge any negative assumptions that exist as well as promote understanding
      about the elements that contribute to a positive working environment. As a result
      of the research there is now practice available for educators to identify
      evidence-based strategies and resources.

PMID- 27714956
TI  - Deficiency of plasminogen receptor, Plg-RKT , causes defects in plasminogen
      binding and inflammatory macrophage recruitment in vivo.
AB  - : Essentials Plg-RKT is a novel integral membrane plasminogen receptor. The
      functions of Plg-RKT in vivo are not known. Plg-RKT is a key player in macrophage
      recruitment in the inflammatory response in vivo. Plg-RKT deficiency is not
      compatible with survival of the species. SUMMARY: Background Plg-RKT is a novel
      integral membrane plasminogen receptor that binds plasminogen via a C-terminal
      lysine exposed on the cell surface and promotes plasminogen activation on the
      cell surface by both tissue plasminogen activator and urokinase plasminogen
      activator. Objectives To evaluate the role of Plg-RKT in vivo we generated Plg
      RKT-/- mice using a homologous recombination technique. Methods We characterized
      the effect of Plg-RKT deletion on reproduction, viability, health and spontaneous
      thrombosis and inflammation. Results Plg-RKT-/- mice were viable and fertile.
      Survival of Plg-RKT-/- mice and Plg-RKT+/+ littermates was not significantly
      different. However, quite strikingly, all pups of Plg-RKT-/- females died within
      2 days of birth, consistent with a lactation defect in Plg-RKT-/- mothers.
      Additionally, there was a significant effect of Plg-RKT deficiency on the growth
      rates of female, but not male, mice. In experimental peritonitis studies, Plg-RKT
      /- mice exhibited a marked defect in macrophage recruitment. As a contributing
      mechanism, the capacity of Plg-RKT-/- macrophages for plasminogen binding was
      markedly decreased. Conclusions These studies demonstrate that Plg-RKT is
      required for plasminogen binding and macrophage migration in vivo. In addition,
      Plg-RKT deficiency is not compatible with survival of the species, due to the
      death of all offspring of Plg-RKT-/- females. This new mouse model will be
      important for future studies aimed at delineating the role of cell surface
      plasminogen activation in challenge and disease models in vivo.

PMID- 27714960
TI  - Risk factors for treatment-related adverse events in cancer-bearing dogs
      receiving piroxicam.
AB  - Piroxicam has antitumour effects in dogs with cancer, although side effects may
      limit its use. The purpose of this study was to retrospectively identify factors
      predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam
      therapy. Medical records of dogs presented to the Purdue Veterinary Teaching
      Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for
      study inclusion. Toxic effects of piroxicam in these dogs were graded according
      to an established system. Multivariate logistic regression was used to estimate
      the extent to which certain factors affected the risk for AEs. Age [odds ratio
      (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent
      use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056)
      significantly increased the risk for gastrointestinal AEs. The results of this
      study may help inform the risk versus benefit calculation for clinicians
      considering the use of piroxicam to treat dogs with cancer.

PMID- 27714961
TI  - Phenotypic variability in patients with Fanconi anemia and biallelic FANCF
      mutations.
AB  - Fanconi anemia is a heterogeneous genetic disorder that is characterized by
      progressive bone marrow failure, congenital anomalies, and markedly increased
      risk for malignancies. Mutations in the FANCF (FA-F) gene represent approximately
      2% of affected patients. Currently, information on the phenotypic findings of
      patients with Fanconi anemia from biallelic mutations in FANCF is limited. Here,
      we report three patients who illustrate the clinical variability within the FA-F
      group. This analysis suggests a more severe phenotype for those with the common
      c.484_485delCT mutation. (c) 2016 Wiley Periodicals, Inc.

PMID- 27714963
TI  - Eric Kyriakos Sclavos (1973-2016).

PMID- 27714965
TI  - Letter to the Editor.

PMID- 27714962
TI  - Utility of blood cultures in children admitted to hospital with community
      acquired pneumonia.
AB  - AIM: The aim of the study was to assess the utility of blood cultures in children
      admitted to hospital with community-acquired pneumonia. The primary outcome was
      the number of positive blood culture results, and secondary outcomes included the
      effect of positive blood culture results on management, and the identification of
      other clinical/biochemical variables that could predict blood culture results or
      the course of illness. METHODS: A retrospective data analysis was carried out on
      all children admitted to Gosford Hospital during the 2-year period from July 2013
      to June 2015. Included were patients under 16 years old who had a diagnosis
      related group code of pneumonia. A review of blood culture results, chest X-ray,
      serology, C-reactive protein and white cell count and clinical outcomes were
      analysed. RESULTS: There were 215 paediatric admissions with a diagnosis of
      pneumonia during the 2-year study period. A blood culture was collected in 82.3%
      (177/215). Although seven had a positive blood culture, only two of these were
      finally reported as true positives and both were Streptococcus pneumoniae. Both
      patients were treated with a cephalosporin and demonstrated clinical improvement.
      No changes were made to their treatment based on the blood culture results.
      CONCLUSION: Blood cultures have a low yield and do not appear to be helpful when
      collected in all patients admitted to hospital with community-acquired pneumonia.

PMID- 27714966
TI  - Concomitant Carboxylate and Oxalate Formation From the Activation of CO2 by a
      Thorium(III) Complex.
AB  - Improving our comprehension of diverse CO2 activation pathways is of vital
      importance for the widespread future utilization of this abundant greenhouse gas.
      CO2 activation by uranium(III) complexes is now relatively well understood, with
      oxo/carbonate formation predominating as CO2 is readily reduced to CO, but
      isolated thorium(III) CO2 activation is unprecedented. We show that the
      thorium(III) complex, [Th(Cp'')3 ] (1, Cp''={C5 H3 (SiMe3 )2 -1,3}), reacts with
      CO2 to give the mixed oxalate-carboxylate thorium(IV) complex [{Th(Cp'')2 [kappa2
      -O2 C{C5 H3 -3,3'-(SiMe3 )2 }]}2 (MU-kappa2 :kappa2 -C2 O4 )] (3). The
      concomitant formation of oxalate and carboxylate is unique for CO2 activation, as
      in previous examples either reduction or insertion is favored to yield a single
      product. Therefore, thorium(III) CO2 activation can differ from better understood
      uranium(III) chemistry.

PMID- 27714967
TI  - Remission spectrometry for blood vessel detection during stereotactic biopsy of
      brain tumors.
AB  - Stereotactic biopsy is used to enable diagnostic confirmation of brain tumors and
      treatment planning. Despite being a well-established technique, it is related to
      significant morbidity and mortality rates mostly caused by hemorrhages due to
      blood vessel ruptures. This paper presents a method of vessel detection during
      stereotactic biopsy that can be easily implemented by integrating two side-view
      fibers into a conventional side-cutting biopsy needle. Tissue within the needle
      window is illuminated through the first fiber; the second fiber detects the
      remitted light. By taking the ratio of the intensities at two wavelengths with
      strongly differing hemoglobin absorption, blood vessels can be recognized
      immediately before biopsy sampling. Via ray tracing simulations and phantom
      experiments, the dependency of the remission ratio R = I578 /I650 on various
      parameters (blood oxygenation, fiber-to-vessel and inter-fiber distance, vessel
      diameter and orientation) was investigated for a bare-fiber probe. Up to 800-1200
      um away from the probe, a vessel can be recognized by a considerable reduction of
      the remission ratio from the background level. The technique was also
      successfully tested with a real biopsy needle probe on both optical phantoms and
      ex-vivo porcine brain tissue, thus showing potential to improve the safety of
      stereotactic biopsy. Dual-wavelength remission measurement for the detection of
      blood vessels during stereotactic biopsy.

PMID- 27714968
TI  - Antiamyloidogenic Activity of Abeta42-Binding Peptoid in Modulating Amyloid
      Oligomerization.
AB  - The oligomerization and aggregation of amyloid beta (Abeta) play central role in
      the pathogenesis of Alzheimer's disease (AD). Molecular binding agents for
      modulating the formation of Abeta oligomers and fibrils have promising
      application potential in AD therapies. By screening a peptoid library using
      surface plasmon resonance imaging, amyloid inhibitory peptoid 1 (AIP1) that has
      high affinity to Abeta42 is identified. AIP1 is demonstrated to inhibit Abeta42
      oligomerization and fibrillation and to rescue Abeta42-induced cytotoxicity
      through decreasing the content of Abeta42 oligomers that is related to cell
      membrane permeability. Molecular docking suggests that the binding sites of AIP1
      may be at the N-terminus of Abeta42. The blood-brain barrier (BBB) permeability
      of AIP1 using an in vitro BBB model is also revealed. This work provides a
      strategy for the design and development of peptoid-based antiamyloidogenic
      agents. The obtained amyloid inhibitory peptoid shows prospects in the
      therapeutic application in AD.

PMID- 27714969
TI  - Raman spectroscopic identification of Mycobacterium tuberculosis.
AB  - In this study, Raman microspectroscopy has been utilized to identify mycobacteria
      to the species level. Because of the slow growth of mycobacteria, the per se
      cultivation-independent Raman microspectroscopy emerges as a perfect tool for a
      rapid on-the-spot mycobacterial diagnostic test. Special focus was laid upon the
      identification of Mycobacterium tuberculosis complex (MTC) strains, as the main
      causative agent of pulmonary tuberculosis worldwide, and the differentiation
      between pathogenic and commensal nontuberculous mycobacteria (NTM). Overall the
      proposed model considers 26 different mycobacteria species as well as antibiotic
      susceptible and resistant strains. More than 8800 Raman spectra of single
      bacterial cells constituted a spectral library, which was the foundation for a
      two-level classification system including three support vector machines. Our
      model allowed the discrimination of MTC samples in an independent validation
      dataset with an accuracy of 94% and could serve as a basis to further improve
      Raman microscopy as a first-line diagnostic point-of-care tool for the
      confirmation of tuberculosis disease.

PMID- 27714971
TI  - Changes in endogenous UV fluorescence and biomechanical stiffness of bovine
      articular cartilage after collagenase digestion are strongly correlated.
AB  - A significant source of morbidity in the elderly population of the United States
      is osteoarthritis (OA), a disease caused by the breakdown and loss of articular
      cartilage. The exact causes of OA remain unknown, though biomechanical forces and
      biochemical alterations are important factors. There exists an unmet need for an
      imaging tool to identify early lesions of OA via metabolic, chemical or
      structural changes. Our work aims to characterize changes in the intensity of UV
      fluorescent bands associated with known structural proteins of cartilage. We
      employed an OA model in which bovine osteochondral plugs were digested in
      collagenase of varying concentrations. UV fluorescence before and after
      proteolytic digestion was measured using a spectrofluorimeter. The elastic
      modulus (EM) of each sample was measured using an indentation apparatus.
      Hydroxypyridinoline crosslink (330/390 nm) fluorescence intensity after digestion
      correlated with cartilage EM (R = 0.922, p = 0.026), as did tryptophan (290/350
      nm) fluorescence intensity after digestion and EM (R = 0.949, p = 0.014) and
      tyrosine (290/310 nm) fluorescence intensity after digestion and EM (R = 0.946, p
      = 0.015). Loss of endogenous UV fluorescence correlated with cartilage
      degradation in an in-vitro model of OA, and may serve as a sensitive optical
      biomarker for the state of cartilage.

PMID- 27714972
TI  - Environmental gradients shape the genetic structure of two medicinal Salvia
      species in Jordan.
AB  - Environmental gradients, and particularly climatic variables, exert a strong
      influence on plant distribution and, potentially, population genetic diversity
      and differentiation. Differences in water availability can cause among-population
      variation in ecological processes and can thus interrupt populations'
      connectivity and isolate them environmentally. The present study examines the
      effect of environmental heterogeneity on plant populations due to environmental
      isolation unrelated to geographic distance. Using AFLP markers, we analyzed
      genetic diversity and differentiation among 12 Salvia spinosa populations and 13
      Salvia syriaca populations from three phytogeographical regions (Mediterranean,
      Irano-Turanian and Saharo-Arabian) representing the extent of the species'
      geographic range in Jordan. Differences in geographic location and climate were
      considered in the analyses. For both species, flowering phenology varied among
      populations and regions. Irano-Turanian and Saharo-Arabian populations had higher
      genetic diversity than Mediterranean populations, and genetic diversity increased
      significantly with increasing temperature. Genetic diversity in Salvia syriaca
      was affected by population size, while genetic diversity responded to drought in
      S. spinosa. For both species, high levels of genetic differentiation were found
      as well as two well-supported phytogeographical groups of populations, with
      Mediterranean populations clustering in one group and the Irano-Turanian and
      Saharo-Arabian populations in another. Genetic distance was significantly
      correlated to environmental distance, but not to geographic distance. Our data
      indicate that populations from moist vs. arid environments are environmentally
      isolated, where environmental gradients affect their flowering phenology, limit
      gene flow and shape their genetic structure. We conclude that environmental
      heterogeneity may act as driver for the observed variation in genetic diversity.

PMID- 27714973
TI  - Phylogenetic Position of Parasitic Chytrids on Diatoms: Characterization of a
      Novel Clade in Chytridiomycota.
AB  - Chytrids are true fungi that reproduce with posteriorly uniflagellate zoospores.
      In the last decade, environmental DNA surveys revealed a large number of
      uncultured chytrids as well as undescribed order-level novel clades in
      Chytridiomycota. Although many species have been morphologically described, only
      some DNA sequence data of parasitic chytrids are available from the database. We
      herein discuss five cultures of parasitic chytrids on diatoms Aulacoseira spp.
      and Asterionella formosa. In order to identify the chytrids examined, thallus
      morphologies were observed using light microscopy. We also conducted a
      phylogenetic analysis using 18S, 5.8S, and 28S rDNA sequences to obtain their
      phylogenetic positions. Based on their morphological characteristics, two
      cultures parasitic on As. formosa were identified as Rhizophydium planktonicum
      and Zygorhizidium planktonicum. The other three cultures infecting Aulacoseira
      spp. (two on Aulacoseira ambigua and the other on Aulacoseira granulata) were
      regarded as Zygorhizidium aff. melosirae. The results of the molecular
      phylogenetic analysis revealed that R. planktonicum belonged to the known order
      Chytridiales, while the two species of Zygorhizidium were placed in a novel clade
      that was previously reported as an undescribed clade composed of only the
      environmental sequences of uncultured chytrids.

PMID- 27714974
TI  - A fair go.

PMID- 27714975
TI  - Erratum.

PMID- 27714976
TI  - Genetics of host-parasite interactions: towards a comprehensive dissection of
      Drosophila resistance to viral infection.
AB  - One of the major challenges in evolutionary biology is to unravel the genetic
      basis of adaptation. This issue has been gaining momentum in recent years with
      the accelerated development of novel genetic and genomic techniques and
      resources. In this issue of Molecular Ecology, Cogni et al. (2016) address the
      genetic basis of resistance to two viruses in Drosophila melanogaster using a
      panel of recombinant inbred lines with unprecedented resolution allowing
      detection of rare alleles and/or alleles of small effect. The study confirms the
      role of previously identified genes of major effect and adds novel regions with
      minor effect to the genetic basis of Drosophila resistance to the Drosophila C
      virus or the sigma virus. Additional analyses reveal the absence of cross
      resistance and of epistasis between the various genomic regions. This detailed
      information on the genetic architecture of host resistance constitutes an
      important step towards the understanding of both the physiology of antiviral
      immunity and the evolution of host-parasite interactions.

PMID- 27714970
TI  - Regional differences in milk and complementary feeding patterns in infants
      participating in an international nutritional type 1 diabetes prevention trial.
AB  - Differences in breastfeeding, other milk feeding and complementary feeding
      patterns were evaluated in infants at increased genetic risk with and without
      maternal type 1 diabetes (T1D). The Trial to Reduce IDDM in the Genetically at
      Risk is an international nutritional primary prevention double-blinded randomized
      trial to test whether weaning to extensively hydrolyzed vs. intact cow's milk
      protein formula will decrease the development of T1D-associated autoantibodies
      and T1D. Infant diet was prospectively assessed at two visits and seven telephone
      interviews between birth and 8 months. Countries were grouped into seven regions:
      Australia, Canada, Northern Europe, Southern Europe, Central Europe I, Central
      Europe II and the United States. Newborn infants with a first-degree relative
      with T1D and increased human leukocyte antigen-conferred susceptibility to T1D
      were recruited. A lower proportion of infants born to mothers with than without
      T1D were breastfed until 6 months of age in all regions (range, 51% to 60% vs.
      70% to 80%). Complementary feeding patterns differed more by region than by
      maternal T1D. In Northern Europe, a higher proportion of infants consumed
      vegetables and fruits daily compared with other regions. Consumption of meat was
      more frequent in all European regions, whereas cereal consumption was most
      frequent in Southern Europe, Canada and the United States. Maternal T1D status
      was associated with breastfeeding and other milk feeding patterns similarly
      across regions but was unrelated to the introduction of complementary foods.
      Infant feeding patterns differed significantly among regions and were largely
      inconsistent with current recommended guidelines.

PMID- 27714977
TI  - The long chain alpha-tocopherol metabolite alpha-13'-COOH and gamma-tocotrienol
      induce P-glycoprotein expression and activity by activation of the pregnane X
      receptor in the intestinal cell line LS 180.
AB  - SCOPE: Members of the vitamin E family or their metabolites may induce the
      xenobiotic transporter P-glycoprotein (P-gp), which can limit the bioavailability
      of drugs and phytochemicals. This study aimed to investigate if alpha- and gamma
      tocopherol, alpha- and gamma-tocotrienol, the long chain metabolite alpha
      tocopherol-13'-COOH, the short chain metabolites alpha- and gamma
      carboxyethylhydroxychromanol and plastochromanol-8 activate the pregnane X
      receptor (PXR) and thereby modulate P-gp expression and/or activity. METHODS AND
      RESULTS: P-gp protein expression and activity were studied in LS 180 cells
      incubated with the respective test compound for 48 h. Furthermore, we determined
      if the compounds activate PXR in LS 180 cells, as PXR regulates P-gp expression.
      Neither P-gp protein expression and activity, nor PXR activity were influenced by
      alpha-tocopherol, gamma-tocopherol and plastochromanol-8. alpha-Tocotrienol
      activated PXR in the reporter gene assay but did not induce protein expression or
      activity of P-gp. gamma-Tocotrienol and alpha-13'-COOH activated PXR and induced
      protein expression and transporter activity of P-gp. CONCLUSION: Because the
      induction of P-gp in the intestine may limit the systemic bioavailability of its
      substrates, the concurrent intake of drugs and gamma-tocotrienol and, if ever
      applicable, alpha-13'-COOH should be avoided.

PMID- 27714978
TI  - Switching regimens in virologically suppressed HIV-1-infected patients: evidence
      base and rationale for integrase strand transfer inhibitor (INSTI)-containing
      regimens.
AB  - In an era when most individuals with treated HIV infection can expect to live
      into old age, clinicians should proactively review their patients' current and
      future treatment needs and challenges. Clinical guidelines acknowledge that, in
      the setting of virological suppression, treatment switch may yield benefits in
      terms of tolerability, regimen simplification, adherence, convenience and long
      term health considerations, particularly in the context of ageing. In this paper,
      we review evidence from six key clinical studies on switching virologically
      suppressed patients to regimens based on integrase strand transfer inhibitors
      (INSTIs), the antiretroviral class increasingly preferred as initial therapy in
      clinical guidelines. We review these studies and focus on the virological
      efficacy, safety, and tolerability of switching to INSTI-based regimens in
      suppressed HIV-positive individuals. We review the early switch studies SWITCHMRK
      and SPIRAL [assessing a switch from a ritonavir-boosted protease inhibitor (PI/r)
      to raltegravir (RAL)-containing regimens], together with data from STRATEGY-PI
      [assessing a switch to elvitegravir (EVG)-containing regimens; EVG/cobicistat
      (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) vs. remaining on a
      PI/r-containing regimen], STRATEGY-NNRTI [assessing a switch to EVG/COBI/FTC/TDF
      vs. continuation of a nonnucleoside reverse transcriptase inhibitor (NNRTI) and
      two nucleoside reverse transcriptase inhibitors (NRTIs)], STRIIVING [assessing a
      switch to a dolutegravir (DTG)-containing regimen (abacavir (ABC)/lamivudine
      (3TC)/DTG) vs. staying on the background regimen], and GS study 109 [assessing a
      switch to EVG/COBI/FTC/tenofovir alafenamide fumarate (TAF) vs. continuation of
      FTC/TDF-based regimens]. Switching to INSTI-containing regimens has been shown to
      support good virological efficacy, with evidence from two studies demonstrating
      superior virological efficacy for a switch to EVG-containing regimens. In
      addition, switching to INSTI regimens was associated with improved tolerability
      and greater reported patient satisfaction and outcomes in some studies. INSTI
      based regimens offer an important contemporary switch option that may be tailored
      to meet and optimize the needs of many patients.

PMID- 27714980
TI  - Preparative separation and purification of two highly polar alkaloids derived
      from Semen Strychni extracted with dichloromethane by high-speed countercurrent
      chromatography.
AB  - Brucine chloromethochloride and strychnine chloromethochloride, the two
      chloromethochloride derivatives formed during the extraction of Semen Strychni in
      which dichloromethane was used as the extracting solvent, were isolated and
      purified by high-speed countercurrent chromatography for the first time. The two
      phase solvent system composed of chloroform/methanol/0.3 mol/L hydrochloric acid
      (4:3:2, v/v/v) was selected for separation. From 300 mg of the crude extracts,
      56.2 mg of brucine chloromethochloride and 60.2 mg of strychnine
      chloromethochloride were obtained with the purity of 99.78 and 96.99%,
      respectively, and the structures were confirmed by mass spectrometry, 1 H, 13 C,
      and two-dimensional NMR spectroscopy. The results indicated that the present
      method is a powerful technology for large-scale isolation of alkaloids from Semen
      Strychni.

PMID- 27714981
TI  - Exceptionally Selective and Tunable Sensing of Guanine Derivatives and Analogues
      by Structural Complementation in a G-Quadruplex.
AB  - A guanine-vacancy-bearing G-quadruplex (GVBQ) interacts with guanine and
      derivatives by a structural complementation to form a more stable and intact G
      quadruplex. Sensors using GVBQs are devised to detect guanine and other
      nucleobases, and their derivatives derived from structurally similar compounds. A
      strict requirement of Hoogsteen hydrogen bonds between the GVBQ and analyte in
      the structural complementation confers exceptional selectivity on the analyte. As
      such, subtle modifications on analytes affecting even a single hydrogen bond can
      preclude the recognition. In principle, the strategy may also be expanded to
      detect many planar cyclic compounds. Because nucleobases and
      derivatives/metabolites are involved in many physiological and pathological
      processes, this type of sensor may find applications in risk assessment of
      pathogenesis and therapeutics related to nucleic acid metabolism.

PMID- 27714979
TI  - Nonoxidative ethanol metabolism in humans-from biomarkers to bioactive lipids.
AB  - Ethanol is a widely used psychoactive drug whose chronic abuse is associated with
      organ dysfunction and disease. Although the prevalent metabolic fate of ethanol
      in the human body is oxidation a smaller fraction undergoes nonoxidative
      metabolism yielding ethyl glucuronide, ethyl sulfate, phosphatidylethanol and
      fatty acid ethyl esters. Nonoxidative ethanol metabolites persist in tissues and
      body fluids for much longer than ethanol itself and represent biomarkers for the
      assessment of ethanol intake in clinical and forensic settings. Of note, the
      nonoxidative reaction of ethanol with phospholipids and fatty acids yields
      bioactive compounds that affect cellular signaling pathways and organelle
      function and may contribute to ethanol toxicity. Thus, despite low quantitative
      contributions of nonoxidative pathways to overall ethanol metabolism the
      resultant ethanol metabolites have important biological implications. In this
      review we summarize the current knowledge about the enzymatic formation of
      nonoxidative ethanol metabolites in humans and discuss the implications of
      nonoxidative ethanol metabolites as biomarkers of ethanol intake and mediators of
      ethanol toxicity. (c) 2016 IUBMB Life, 68(12):916-923, 2016.

PMID- 27714982
TI  - Superlyophilicity-Facilitated Synthesis Reaction at the Microscale: Ordered
      Graphdiyne Stripe Arrays.
AB  - As a new member of carbon allotropes, graphdiyne is a promising material with
      excellent electronic performance and high elasticity, indicating the possibility
      of graphdiyne to serve as the building blocks in flexible electronics. However,
      precise positioning/patterning of graphdiyne is still a challenge for the
      realization of large-area and flexible organic electronic devices and circuits.
      Here, the direct in situ synthesis of patterning graphdiyne stripe arrays
      dominated by the superlyophilic grooved templates is reported, whereas the
      superlyophilicity of grooved templates plays a key role in allowing continuous
      mass transport of raw reactants into the microscale spacing. After the completion
      of cross-coupling reaction procedure, precisely patterned graphdiyne stripes can
      be generated accordingly. The size of graphdiyne stripe arrays is depending on
      the silicon substrate size (1 cm * 1.5 cm), and the layer thickness can be
      manipulated from just several nanometers to hundreds of nanometers by varying the
      primary concentration of hexaethynylbenzene monomers. As a proof-of-principle
      demonstration, a stretchable sensor based on the graphdiyne stripe arrays is
      performed to monitor the human finger motion. It is expected that this
      wettability-facilitated strategy will provide new insights into the controlled
      synthesis of graphdiyne toward promising flexible electronics and other
      optoelectronic applications.

PMID- 27714983
TI  - Porcine models for the study of small-for-size syndrome and portal inflow
      modulation: literature review and proposal for a standardized nomenclature.
AB  - Porcine models of extended hepatectomy and liver transplantation (LT) of reduced
      graft have been widely used for studying the small-for-size (SFS) syndrome and
      the various modalities of portal inflow modulation (PIM). However, considerable
      heterogeneity exists among the studies and their results. The aim of this review
      was to assess the main advantages and drawbacks of the different porcine models
      of SFS LT and SFS hepatectomy, and propose a standardized anatomical nomenclature
      for the various models. The MEDLINE database was searched for articles reporting
      porcine models of reduced graft LT or hepatectomy of more than 65%. Nineteen
      articles on SFS LT matched our inclusion criteria, including 10 articles
      reporting a model of PIM. Twenty-seven articles reporting a model of
      posthepatectomy SFS were identified, of which 16 reported a model of PIM.
      Subtotal hepatectomy (i.e. resection of all segments except segment 1) without
      inflow occlusion, left trisectionectomy with inflow occlusion, and LT of a right
      lateral section including the caudate lobe in a larger recipient appeared to be
      the most suitable porcine models for studying the SFS syndrome. All three models
      were appropriate for assessing the surgical and pharmaceutical PIM modalities,
      except for those involving the splenic flow.

PMID- 27714984
TI  - Quantification of three beta-lactam antibiotics in breast milk and human plasma
      by hydrophilic interaction liquid chromatography/positive-ion electrospray
      ionization mass spectrometry.
AB  - The use of cephalosporins during breast feeding raises several issues, including
      the risk of drug exposure through breast milk for the infant. In this paper, a
      hydrophilic interaction liquid chromatography/positive ion electrospray mass
      spectrometric assay (HILIC/ESI-MS) was developed for the quantitation of
      cefuroxime, cefoxitin, and cefazolin in breast milk and human plasma. The assay
      was based on the use of small sample size, 25 MUL of biological samples,
      following acetonitrile precipitation of proteins and filtration that enabled
      injection into the HILIC/ESI-MS system. All analytes and the internal standard,
      alfuzosin, were separated by using a ZIC(r)-HILIC analytical column (150.0 * 2.1
      mm i.d., particle size 3.5 um, 200 A) with isocratic elution. The mobile phase
      was composed of a 6% 12.5 mM ammonium acetate water solution in acetonitrile and
      pumped at a flow rate of 0.25 mL min-1 . The assay was linear over a
      concentration range of 0.2 to 5 ug mL-1 and 0.4 to 20 ug mL-1 for all the
      analytes in breast milk and in human plasma, respectively. Intermediate precision
      was found to be less than 4.2% over the tested concentration ranges. A run time
      of less than 12 min for each sample made it possible to analyze a large number of
      biological samples per day. The method is the first reported application of HILIC
      in the analysis of antibiotics in breast milk and human plasma and it can be used
      to support a wide range of clinical studies. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27714985
TI  - Development of an evidence-based fall risk assessment tool and evaluation of
      interrater reliability and nurses' perceptions of the tool's clarity and
      usability.
AB  - AIM: To develop and test interrater reliability of an evidence-based fall risk
      assessment tool for nurses and to investigate how nurses perceived the clarity
      and usability of the tool. METHODS: In phase 1, an evidence-based fall risk
      assessment tool was developed based on a literature review and expert discussion.
      The finalized tool assessed 11 risk factors and comprised 23 items. In phase 2,
      reliability testing was done. Two nurses out of a possible 125 participating
      nurses independently assessed each participating patient on admission with the
      assessment tool. The nurses then provided feedback on the clarity and usability
      of the tool. The interrater reliability was estimated by the percentage
      agreement, Cohen's kappa, and prevalence- and bias-adjusted kappa. RESULTS: Of
      the 164 patients who were recruited, 114 patients participated. After adjustment
      for prevalence and bias, only "frequent urination" and "night-time toileting"
      showed a less-than-substantial interrater agreement. Assessment of the items
      "cognitive impairment" and "night-time toileting" were most frequently reported
      to be problematic. CONCLUSION: The evidence-based fall risk assessment tool
      requires further modification and re-examination of interrater reliability is
      warranted. In particular, the cognitive impairment items need to be reconsidered
      in order to enable nurses to better assess patient cognition on the admission
      day.

PMID- 27714986
TI  - Effects of Water Loss on New Mexico Spadefoot Toad (Spea multiplicata)
      Development, Spleen Cellularity, and Corticosterone Levels.
AB  - Amphibian metamorphosis is complex and larval morphology and physiology are
      completely restructured during this time. Amphibians that live in unpredictable
      environments are often exposed to stressors that can directly and indirectly
      alter physiological systems during development, with subsequent consequences
      (carryover effects) later in life. In this study, we investigated the effects of
      water level reduction on development rate, spleen size and cellularity, and
      examined the role of corticosterone levels in premetamorphic, metamorphic, and
      postmetamorphic New Mexico spadefoot toads (Spea multiplicata). Based on previous
      studies, we hypothesized that declining water level would increase tadpole
      developmental rate, but with the trade-off of increasing corticosterone to a
      level that would subsequently affect spleen size and cellularity, thus prolonging
      potential immunological suppression. Declining water levels increased
      developmental rate by 3 days; however, there were no significant body size
      effects. Corticosterone (CORT) was negatively correlated with total length, snout
      vent length, body weight, and spleen weight at metamorphosis, suggesting that
      size at metamorphosis and the immune system may be affected by excessive CORT
      levels. When compared to other studies, our results support the view that
      multiple factors may be acting as stressors in the field affecting amphibian
      responses, and simple pathways as tested in this study may not adequately
      represent field conditions.

PMID- 27714987
TI  - In vitro characterization of biofilms formed by Kingella kingae.
AB  - The Gram-negative bacterium Kingella kingae is part of the normal oropharyngeal
      mucosal flora of children <4 years old. K. kingae can enter the submucosa and
      cause infections of the skeletal system in children, including septic arthritis
      and osteomyelitis. The organism is also associated with infective endocarditis in
      children and adults. Although biofilm formation has been coupled with pharyngeal
      colonization, osteoarticular infections, and infective endocarditis, no studies
      have investigated biofilm formation in K. kingae. In this study we measured
      biofilm formation by 79 K. kingae clinical isolates using a 96-well microtiter
      plate crystal violet binding assay. We found that 37 of 79 strains (47%) formed
      biofilms. All strains that formed biofilms produced corroding colonies on agar.
      Biofilm formation was inhibited by proteinase K and DNase I. DNase I also caused
      the detachment of pre-formed K. kingae biofilm colonies. A mutant strain carrying
      a deletion of the pilus gene cluster pilA1pilA2fimB did not produce corroding
      colonies on agar, autoaggregate in broth, or form biofilms. Biofilm forming
      strains have higher levels of pilA1 expression. The extracellular components of
      biofilms contained 490 MUg cm-2 of protein, 0.68 MUg cm-2 of DNA, and 0.4 MUg cm
      2 of total carbohydrates. We concluded that biofilm formation is common among K.
      kingae clinical isolates, and that biofilm formation is dependent on the
      production of proteinaceous pili and extracellular DNA. Biofilm development may
      have relevance to the colonization, transmission, and pathogenesis of this
      bacterium. Extracellular DNA production by K. kingae may facilitate horizontal
      gene transfer within the oral microbial community.

PMID- 27714989
TI  - Optical redox ratio and endogenous porphyrins in the detection of urinary bladder
      cancer: A patient biopsy analysis.
AB  - Bladder cancer is among the most common cancers in the UK and conventional
      detection techniques suffer from low sensitivity, low specificity, or both.
      Recent attempts to address the disparity have led to progress in the field of
      autofluorescence as a means to diagnose the disease with high efficiency, however
      there is still a lot not known about autofluorescence profiles in the disease.
      The multi-functional diagnostic system "LAKK-M" was used to assess
      autofluorescence profiles of healthy and cancerous bladder tissue to identify
      novel biomarkers of the disease. Statistically significant differences were
      observed in the optical redox ratio (a measure of tissue metabolic activity), the
      amplitude of endogenous porphyrins and the NADH/porphyrin ratio between tissue
      types. These findings could advance understanding of bladder cancer and aid in
      the development of new techniques for detection and surveillance.

PMID- 27714990
TI  - Multifunctional Textured Surfaces with Enhanced Friction and Hydrophobic
      Behaviors Produced by Fiber Debonding and Pullout.
AB  - Fiber debonding and pullout are well-understood processes that occur during
      damage and failure events in composite materials. In this study, we show how
      these mechanisms, under controlled conditions, can be used to produce
      multifunctional textured surfaces. A two-step process consisting of (1) achieving
      longitudinal fiber alignment followed by (2) cutting, rearranging, and joining is
      used to produce the textured surfaces. This process employs common composite
      manufacturing techniques and uses no reactive chemicals or wet handling, making
      it suitable for scalability. This uniform textured surface is due to the fiber
      debonding and pullout occurring during the cutting process. Using well
      established fracture mechanics principles for composite materials, we demonstrate
      how different material parameters such as fiber geometry, fiber and matrix
      stiffness and strength, and interface behavior can be used to achieve
      multifunctional textured surfaces. The resulting textured surfaces show very high
      friction coefficients on wet ice (9* improvement), indicating their promising
      potential as materials for ice traction/tribology. Furthermore, the texturing
      enhances the surface's hydrophobicity as indicated by an increase in the contact
      angle of water by 30%. The substantial improvements to surface tribology and
      hydrophobicity make fiber debonding and pullout an effective, simple, and
      scalable method of producing multifunctional textured surfaces.

PMID- 27714988
TI  - Intranasal delivery of Natesto(r) testosterone gel and its effects on doping
      markers.
AB  - The laboratory profile of intranasal testosterone gel has not been previously
      reported from an anti-doping perspective. Because intranasal testosterone gel is
      newly available as a commercial product, we sought to examine the laboratory
      parameters following administration of this formulation, with particular
      attention to anti-doping guidelines. Five healthy and active male subjects were
      administered testosterone intranasal gel three times daily for four weeks, using
      a pattern of five consecutive days on, two days off. Urine was collected after
      each five-day round of drug administration and analyzed using a full steroid
      screen and isotope ratio mass spectrometry (IRMS). Windows of detection for
      elevated testosterone/epitestosterone (T/E) and other steroid ratios, World Anti
      Doping Agency (WADA) athlete biological passport (ABP) findings, and IRMS results
      were analyzed in this study. In the 0-24 h window post-administration, 70% of
      samples were flagged with a suspicious steroid profile and 85% were flagged as
      atypical passport findings according to the WADA ABP steroid module. In the 24-48
      h window, 0% of samples displayed suspicious steroid profiles while 40% resulted
      in atypical passport findings. IRMS testing confirmed the presence of exogenous
      testosterone in 90% and 40% of samples in the 0-24 h and 24-48 h windows post
      administration, respectively. Additionally, IRMS data were analyzed to determine
      commonalities in the population changes in delta13 C values of testosterone,
      androsterone, etiocholanolone, 5alphaAdiol, and 5betaAdiol. Though no discernible
      metabolic trend of the route of administration was identified, we discovered that
      intranasal gel testosterone is detectable using conventional anti-doping tests.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27714991
TI  - Porous N-Doped Carbon Prepared from Triazine-Based Polypyrrole Network: A Highly
      Efficient Metal-Free Catalyst for Oxygen Reduction Reaction in Alkaline
      Electrolytes.
AB  - Metal-free N-doped carbon (NC) materials have been regarded as one of the most
      promising catalysts for the oxygen reduction reaction (ORR) in alkaline media
      because of their outstanding ORR catalytic activity, high stability, and good
      methanol tolerance. Up to now, only a small minority of such catalysts have been
      synthesized from triazine-based polymeric networks. Herein, we report the
      synthesis of such NC catalyst by directly pyrolyzing a nitrogen-rich, triazine
      based polypyrrole network (TPN). The TPN is fabricated by oxidative
      polymerization of 2,4,6-tripyrrol-1,3,5-triazine monomer using TfOH as the
      protonating agent and benzoyl peroxide as the oxidizing agent. The obtained NC
      900 (pyrolyzed at 900  degrees C) catalyst exhibits excellent ORR activity in
      alkaline media with a high ORR onset potential (0.972 V vs RHE), a large kinetic
      limiting current density (15.66 mA cm-2 at 0.60 V), and good MeOH tolerance and
      durability. The as-synthesized NC-900 material is a potential candidate as a
      highly active, stable, and low-cost ORR catalyst for alkaline fuel cells.

PMID- 27714992
TI  - Single Molecule Nanoelectrochemistry in Electrical Junctions.
AB  - It is now possible to reliably measure single molecule conductance in a wide
      variety of environments including organic liquids, ultrahigh vacuum, water, ionic
      liquids, and electrolytes. The most commonly used methods deploy scanning probe
      microscopes, mechanically formed break junctions, or lithographically formed
      nanogap contacts. Molecules are generally captured between a pair of facing
      electrodes, and the junction current response is measured as a function of bias
      voltage. Gating electrodes can also be added so that the electrostatic potential
      at the molecular bridge can be independently controlled by this third
      noncontacting electrode. This can also be achieved in an electrolytic environment
      using a four-electrode bipotentiostatic configuration, which allows independent
      electrode potential control of the two contacting electrodes. This is commonly
      realized using an electrochemical STM and enables single molecule electrical
      characterization as a function of electrode potential and redox state of the
      molecular bridge. This has emerged as a powerful tool in modern interfacial
      electrochemistry and nanoelectrochemistry for studying charge transport across
      single molecules as a function of electrode potential and the electrolytic
      environments. Such measurements are possible in electrolytes ranging from aqueous
      buffers to nonaqueous ionic liquids. In this Account, we illustrate a number of
      examples of single molecule electrical measurements under electrode potential
      control use a scanning tunneling microscope (STM) and demonstrate how these can
      help in the understanding of charge transport in single molecule junctions.
      Examples showing charge transport following phase coherent tunneling to
      incoherent charge hopping across redox active molecular bridges are shown. In the
      case of bipyridinium (or viologen) molecular wires, it is shown how
      electrochemical reduction leads to an increase of the single molecule
      conductance, which is controlled by the liquid electrochemical gating. This has
      been referred to as to a "single molecule transistor configuration" with the gate
      voltage being provided by the controllable potential achieved through the
      electrochemical double layer. It is shown how the electrolyte medium can control
      such gating, with ionic liquids providing more efficient gate coupling than
      aqueous electrolytes. Control of the conductance of viologen molecular wires can
      also be achieved by encapsulating the viologen redox moiety within a molecular
      cage, thereby controlling its immediate environment. Molecular conductance can
      also be gated through multiple redox states. This has been shown for the redox
      moiety pyrrolo-tetrathiafulvalene, which undergoes single molecule
      electrochemical transistor gating through three redox states in molecular
      junctions. Charge transport through this junction follows a two-step hopping
      mechanism, demonstrating the role of the redox center in electron transfer across
      the molecular bridge. Recent electrolyte gating studies of rigid, conjugated
      redox-active metal complexes with tailored terpyridine coordinating ligands and
      anchors are also presented. These aforementioned studies have all been performed
      with gold electrode contacts. The Account concludes with recent data showing that
      it is now possible to study single molecule electrochemical gating with nickel
      electrodes. This opens up new perspectives for studying interfacial charge
      transfer with a wide variety of other electrode materials including semiconductor
      electrodes and also points toward future opportunities for coupling molecular
      spintronics and nanoelectrochemistry.

PMID- 27714993
TI  - Colorimetric Logic Gate for Pyrophosphate and Pyrophosphatase via Regulating the
      Catalytic Capability of Horseradish Peroxidase.
AB  - By regulating the catalytic capability of horseradish peroxidase (HRP), an artful
      colorimetric assay platform for pyrophosphate (PPi) and pyrophosphatase (PPase)
      was unprecedentedly designed. In this work, Cu(I), generated by reducing Cu(II)
      in the presence of ascorbate, could inhibit HRP's catalytic capability of
      transforming colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidized
      TMB (oxTMB). The robust coordination between PPi and Cu(II) is able to discourage
      the reduction of Cu(II) to Cu(I) effectively, thus restoring the original
      catalytic capability of HRP and regenerating blue-colored oxTMB. Upon PPase
      introduction, PPi would be hydrolyzed into orthophosphate, which could release
      Cu(II) free from the Cu(II)-PPi complex, and thus in turn allows the catalytic
      capability of HRP to be inhibited by Cu(I). HRP was activated or deactivated to
      different degrees depending on PPi or PPase levels, which could be indicated by
      using HRP-triggered catalytic system as a signal amplifier, thus paving a way for
      PPi and PPase sensing. Based on the colorimetric sensor for PPi and PPase, an
      "INH" logic gate was rationally constructed. With the merits of high sensitivity
      and selectivity, cost-effectiveness, and simplification, our proposed analytical
      system has also been verified to have potential to be utilized for enzyme
      inhibitor screening and diagnosis of PPase-related diseases.

PMID- 27714994
TI  - Surface-Independent Hierarchical Coatings with Superamphiphobic Properties.
AB  - Facile approaches for the fabrication of substrate independent superamphiphobic
      surfaces that can repel both water and organic liquids have been limited. The
      design of such super-repellent surfaces is still a major challenge of surface
      chemistry and physics. Herein, we describe a simple and efficient dip-coating
      approach for the fabrication of highly hierarchical surface coatings with
      superamphiphobic properties for a broad range of materials based on a mussel
      inspired dendritic polymer (MI-dPG). The MI-dPG coating process provides a
      precise roughness control, and the construction of highly hierarchical structures
      was achieved either directly by pH-controlled aggregation or in combination with
      nanoparticles (NP). Moreover, the fabrication of coatings with a thickness and
      roughness gradient was possible via simple adjustment of the depth of the coating
      solution. Subsequent postmodification of these highly hierarchical structures
      with fluorinated molecules yielded a surface with superamphiphobic properties
      that successfully prevented the wetting of liquids with a low surface tension
      down to about 30 mN/m. The generated superamphiphobic coatings exhibit impressive
      repellency to water, surfactant containing solutions, and biological liquids,
      such as human serum, and are flexible on soft substrates.

PMID- 27714995
TI  - Correction to "Fabrication of Microcapsules for Dye-Doped PDLC-Based Smart
      Windows".

PMID- 27714996
TI  - Flexible Microsupercapacitors Using Silk and Cotton Substrates.
AB  - Flexible microsupercapacitors (MSCs) are needed to power ultrasmall wearable
      electronic devices. Silk cocoons comprise microfibers of silk, which is an
      attractive natural resource to fabricate MSCs. These fibers are insulators;
      hence, they must be converted to conducting surfaces. Polyphenols from green tea
      have been used as a protective layer that also acted as a reducing agent for
      silver ions. The reduction of silver ions resulted in the formation of silver
      nanoparticles that subsequently reduced gold ions to gold. The gold film imparts
      conductivity to the silk fiber without affecting the mechanical strength of the
      silk fiber. The mechanical strength of uncoated silk fiber and gold coated silk
      fiber were found to be 5.2 and 5 GPa, respectively. A pseudocapacitive polymer,
      poly(3,4-ethylenedioxythiophene), was used as the active material to fabricate
      MSCs. The MSCs showed an impressive gravimetric capacitance of 500 F/g and areal
      capacitance of 62 mF/cm2. The power and energy densities were calculated to be
      2458 W/kg and 44 Wh/kg, respectively. The device was coiled on a cylinder, and
      the performance of the device was found to be same as that of the uncoiled
      device. To demonstrate that the approach is not specific to silk, we also coated
      gold on cotton fibers using the protocol used to coat gold on silk. Coiled and
      uncoiled supercapacitors were fabricated using PEDOT coated cotton fibers. The
      gravimetric capacitance was found to be 250 F/g with energy and power densities
      of 5.5 Wh/kg and 1118 W/kg, respectively. We have also demonstrated that the
      devices can be connected in parallel and series to improve the performance of the
      miniaturized devices.

PMID- 27714997
TI  - Surfaces Mimicking Glycosaminoglycans Trigger Different Response of Stem Cells
      via Distinct Fibronectin Adsorption and Reorganization.
AB  - We report on the utility of a platform created by self-assembled monolayers to
      investigate the influence of the degree of sulfation of glycosaminoglycans (GAGs)
      on their interactions with fibronectin (Fn) and the impact of these interactions
      on the adhesion and morphology of human adipose derived stem cells (ASCs). We
      used the label-free QCM-D, AFM and SPR to follow the changes in the protein
      adlayer in close proximity to the substrates surface and QCM-D in combination
      with live imaging to characterize the adherent cells. Our results suggest that Fn
      interactions with GAGs are governed by both H-bonding and electrostatic forces.
      Strong electrostatic interactions cause irreversible change in the protein
      conformation, while the weaker H-bonding only partially restricts the protein
      flexibility, allowing Fn reorganization and exposure of its binding sites for ASC
      adhesion. These findings imply that a delicate balance between these two types of
      forces must be considered in the design of biomaterials that mimic GAGs.

PMID- 27714998
TI  - Prominent Vascularization Capacity of Mesenchymal Stem Cells in Collagen-Gold
      Nanocomposites.
AB  - The ideal characteristics of surface modification on the vascular graft for
      clinical application would be with excellent hemocompatibility,
      endothelialization capacity, and antirestenosis ability. Here, Fourier transform
      infrared spectroscopy (FTIR), surface enhanced Raman spectroscopy (SERS), atomic
      force microscopy (AFM), contact angle (theta) measurement, and thermogravimetric
      analysis (TGA) were used to evaluate the chemical and mechanical properties of
      collagen-gold nanocomposites (collagen+Au) with 17.4, 43.5, and 174 ppm of Au and
      suggested that the collagen+Au with 43.5 ppm of Au had better biomechanical
      properties and thermal stability than pure collagen. Besides, stromal-derived
      factor-1alpha (SDF-1alpha) at 50 ng/mL promoted the migration of mesenchymal stem
      cells (MSCs) on collagen+Au material through the alpha5beta3 integrin/endothelial
      oxide synthase (eNOS)/metalloproteinase (MMP) signaling pathway which can be
      abolished by the knockdown of vascular endothelial growth factor (VEGF). The
      potentiality of collagen+Au with MSCs for vascular regeneration was evaluated by
      our in vivo rat model system. Artery tissues isolated from an implanted
      collagen+Au-coated catheter with MSCs expressed substantial CD-31 and alpha-SMA,
      displayed higher antifibrotic ability, antithrombotic activity, as well as anti
      inflammatory response than all other materials. Our results indicated that the
      implantation of collagen+Au-coated catheters with MSCs could be a promising
      strategy for vascular regeneration.

PMID- 27714999
TI  - Potassium Secondary Batteries.
AB  - Potassium may exhibit advantages over lithium or sodium as a charge carrier in
      rechargeable batteries. Analogues of Prussian blue can provide millions of cyclic
      voltammetric cycles in aqueous electrolyte. Potassium intercalation chemistry has
      recently been demonstrated compatible with both graphite and nongraphitic
      carbons. In addition to potassium-ion batteries, potassium-O2 (or -air) and
      potassium-sulfur batteries are emerging. Additionally, aqueous potassium-ion
      batteries also exhibit high reversibility and long cycling life. Because of
      potentially low cost, availability of basic materials, and intriguing
      electrochemical behaviors, this new class of secondary batteries is attracting
      much attention. This mini-review summarizes the current status, opportunities,
      and future challenges of potassium secondary batteries.

PMID- 27715001
TI  - Hybrid Thin Film Organosilica Sol-Gel Coatings To Support Neuronal Growth and
      Limit Astrocyte Growth.
AB  - Thin films of silica prepared by a sol-gel process are becoming a feasible
      coating option for surface modification of implantable neural sensors without
      imposing adverse effects on the devices' electrical properties. In order to
      advance the application of such silica-based coatings in the context of neural
      interfacing, the characteristics of silica sol-gel are further tailored to gain
      active control of interactions between cells and the coating materials. By
      incorporating various readily available organotrialkoxysilanes carrying distinct
      organic functional groups during the sol-gel process, a library of hybrid
      organosilica coatings is developed and investigated. In vitro neural cultures
      using PC12 cells and primary cortical neurons both reveal that, among these
      different types of hybrid organosilica, the introduction of aminopropyl groups
      drastically transforms the silica into robust neural permissive substrate,
      supporting neuron adhesion and neurite outgrowth. Moreover, when this
      organosilica is cultured with astrocytes, a key type of glial cells responsible
      for glial scar response toward neural implants, such cell growth promoting effect
      is not observed. These findings highlight the potential of organo-group-bearing
      silica sol-gel to function as advanced coating materials to selectively modulate
      cell response and promote neural integration with implantable sensing devices.

PMID- 27715000
TI  - Hybrid n-Alkylamine Intercalated Layered Titanates for Solid Lubrication.
AB  - The intercalation of different primary n-alkylamines in the structure of a
      layered titanate of the lepidocrocite type (H1.07Ti1.73O4) for application in
      high-temperature solid lubrication is reported. The intercalation process of the
      amines was explored by means of in situ small-angle X-ray scattering (SAXS), with
      variations in alkyl chain length (3-12 carbon atoms) and the amine/titanate
      ratio. The intercalation process was found to be completed within 5 min after
      mixing of the precursors in water at 80  degrees C. The topotactic transformation
      of the layered titanate is driven by an acid-base reaction. The thermal
      degradation of the modified titanates was investigated by thermogravimetric
      analysis (TGA), and the chemical changes were investigated by temperature
      dependent infrared spectroscopy (DRIFTS). The coefficient of friction of the
      lubricants was assessed by means of high-temperature pin-on-disc experiments up
      to 580  degrees C. The intercalation of amine rendered a deformable layered
      ceramic upon heating. It was found that the hydrocarbon chain length exerts an
      influence on the mechanical properties of the titanates, resulting in lower
      friction forces for lubricants with longer intercalated amine molecules. Films of
      solid lubricants with longer amine chain lengths showed coefficients of friction
      as low as 0.01, lower than that of the state-of-the-art material graphite.

PMID- 27715002
TI  - Dominant Factors Governing the Electron Transfer Kinetics and Electrochemical
      Biosensing Properties of Carbon Nanofiber Arrays.
AB  - Carbon-based electrodes have been widely used in electroanalysis for more than
      half a century, but the factors governing the heterogeneous electron-transfer
      (HET) rate are still unclear. The effects of the exposed edge plane site density,
      inherent resistance of the carbon electrode, and adjustable resistors on the HET
      kinetics of several outer- and inner-sphere redox couples including [Fe(CN)6]3-/4
      , Ru(NH3)63+/2+, Fe3+/2+, dopamine, ascorbic acid, and uric acid are investigated
      using three kinds of carbon electrodes composed of core-shell quasi-aligned
      nanofiber arrays (QANFAs). The internal resistance is found to be a key factor
      affecting the HET kinetics and electrochemical biosensing properties. The
      electrodes exhibit high selectivity and sensitivity in dopamine detection in the
      presence of ascorbic acid and uric acid. In addition to the promising application
      to electrochemical biosensing, the core-shell TiC/C QANFAs encompassing a highly
      electroactive carbon shell and conductive TiC core provide insights into the
      design and construction of the ideal carbon electrode.

PMID- 27715003
TI  - Three-Dimensional Porous Graphene Aerogel Cathode with High Sulfur Loading and
      Embedded TiO2 Nanoparticles for Advanced Lithium-Sulfur Batteries.
AB  - Three-dimensional graphene aerogel/TiO2/sulfur (GA/TiO2/S) composites are
      synthesized through a facile, one-pot hydrothermal route as the cathode for
      lithium-sulfur batteries. With a high sulfur content of 75.1 wt %, the
      conductive, highly porous composite electrode delivers a high discharge capacity
      of 512 mA h/g after 250 cycles at a current rate of 1 C with a low capacity decay
      of 0.128% per cycle. The excellent capacities and cyclic stability arise from
      several unique functional features of the cathode. (i) The conductive graphene
      aerogel framework ameliorates ion/electron transfer while accommodating the
      volume expansion induced during discharge, and (ii) TiO2 nanoparticles play an
      important role in restricting the dissolution of polysulfides by chemical bonds
      with sulfur.

PMID- 27715004
TI  - Biofilm Impeding AgNPs Target Skin Carcinoma by Inducing Mitochondrial Membrane
      Depolarization Mediated through ROS Production.
AB  - Reactive oxygen species (ROS) are a double-edged sword that possesses both
      beneficial and harmful effects. Although basic research on skin cancer prevention
      has undergone a huge transformation, cases of recurrence with higher rates of
      drug resistance are some of its drawbacks. Therefore, targeting mitochondria by
      ROS overproduction provides an alternate approach for anticancer therapy. In the
      present study, green-synthesized silver nanoparticles (AgNPs) were explored for
      triggering the ROS production in A431 skin carcinoma cells. The synthesized AgNPs
      were characterized for size, charge, morphology, and phase through high
      throughput DLS, Fe-SEM, XRD, and ATR-FTIR techniques. Their physiochemical
      properties with hemoglobin and blood plasma were screened through hemolysis,
      hemagglutination assay, and circular dichroism spectroscopy confirmed their
      nontoxic nature. The AgNPs also exhibited additional efficacy in inhibiting
      biofilm produced by V. cholerae and B. subtilis, thereby facilitating better
      applicability in wound-healing biomaterials. The depolarization of mitochondrial
      membrane potential DeltaPsim through excess ROS production was deduced to be the
      triggering force behind the apoptotic cell death mechanism of the skin carcinoma.
      Subsequent experimentation through DNA fragmentation, comet tail formation, cell
      membrane blebbing, and reduced invasiveness potentials through scratch assay
      confirmed the physiological hallmarks of apoptosis. Thus, depolarizing
      mitochondrial membrane potential through green-synthesized AgNPs provides an
      economic, nontoxic, specific approach for targeting skin carcinoma with
      additional benefits of antibacterial activities.

PMID- 27715005
TI  - Thermal Diffusivity of Single Carbon Nanocoil: Uncovering the Correlation with
      Temperature and Domain Size.
AB  - As an exotic class of low-dimensional carbon nanostructures, carbon nanocoils'
      (CNCs) helical geometries and polycrystalline-amorphous structure distinguish
      them from carbon nanotubes and graphene. These distinct structures result in very
      much different energy transport from that in carbon nanotubes and graphene,
      leading to important roles in applications as wave absorbers, near-infrared
      sensors, and nano-electromechanical sensors. Here we report a systematic study of
      the thermal diffusivity (alpha) and conductivity (kappa) of CNCs from 290 to 10
      K, and uncover their property-structure aspects. Our room temperature alpha study
      reveals an correlation between alpha and the line diameter (d): alpha=(5.43 *104e
      d/37.7+9.5)*10-7 m2/s. Combined with the Raman-based grain size (La)
      characterization, alpha and La are correlated as alpha=[81.2*(La-3.32)1.5+9.5]
      *10-7 m2/s. With temperature decreasing from 290 to 10 K, alpha has a 1~1.6-fold
      increase, and kappa shows a peak around 75 K. To best understand the defect level
      and polycrystalline-amorphous structure of CNCs, the thermal reffusivity
      (Theta=alpha-1) of CNCs is studied and compared with that of graphite and
      graphene foam from 290 K down to 10 K. Very interestingly, CNC's Theta linearly
      decreases with decreased temperature while Theta of graphite and graphene foam
      have an exponential decrease. The extrapolated 0 K-limit Theta is determined by
      low-momentum phonon scattering, and gives a structure domain size of CNC samples
      (d=455, 353, and 334 nm) as 1.28 nm, 2.03 nm and 3.24 nm. These sizes are
      coherent with the x-ray diffraction results (3.5 nm) and the Raman spectroscopy
      study, and confirm the correlation among d, La, and alpha.

PMID- 27715006
TI  - Van der Waals Epitaxy of GaSe/Graphene Heterostructure: Electronic and
      Interfacial Properties.
AB  - Stacking two-dimensional materials in so-called van der Waals (vdW)
      heterostructures, like the combination of GaSe and graphene, provides the ability
      to obtain hybrid systems which are suitable to design optoelectronic devices.
      Here, we report the structural and electronic properties of the direct growth of
      multilayered GaSe by Molecular beam Epitaxy (MBE) on graphene. Reflection high
      energy electron diffraction (RHEED) images exhibited sharp streaky features
      indicative of high quality GaSe layer produced via a vdW epitaxy. Micro-Raman
      spectroscopy showed that, after the vdW hetero-interface formation, the Raman
      signature of pristine graphene is preserved. However, the GaSe film tuned the
      charge density of graphene layer by shifting the Dirac point by about 80 meV
      toward lower binding energies, attesting an electron transfer from graphene to
      GaSe. Angle-resolved photoemission spectroscopy (ARPES) measurements showed that
      the maximum of the valence band of few layers of GaSe are located at the Gamma
      point at a binding energy of about -0.73 eV relatively to the Fermi level (p-type
      doping). From the ARPES measurements, a hole effective mass defined along the
      GammaM direction and equal to about m*/m0 = -1.1 was determined. By coupling the
      ARPES data with high resolution X-ray photoemission spectroscopy (HR-XPS)
      measurements, the Schottky interface barrier height was estimated to be 1.2 eV.
      These findings allow deeper understanding of the interlayer interactions and the
      electronic structure of GaSe/graphene vdW heterostructure.

PMID- 27715007
TI  - Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking
      Behavior without Concomitant D2 Side Effects.
AB  - Dopamine receptor antagonism is a compelling molecular target for the treatment
      of a range of psychiatric disorders, including substance use disorders. From our
      corporate compound file, we identified a structurally unique D3 receptor (D3R)
      antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore
      elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467
      (3). Compound 3 was designed to possess CNS drug-like properties as defined by
      its CNS MPO desirability score (>=4/6). In addition to good physicochemical
      properties, 3 exhibited low nanomolar affinity for the D3R (D3 Ki = 3.1 nM), good
      subtype selectivity over D2R (D2 Ki = 692 nM), and high selectivity for D3R
      versus other biogenic amine receptors. In vivo, 3 dose-dependently attenuated
      opioid self-administration and opioid drug-seeking behavior in a rat operant
      reinstatement model using animals trained to self-administer fentanyl. Further,
      traditional extrapyramidal symptoms (EPS), adverse side effects arising from D2R
      antagonism, were not observed despite high D2 receptor occupancy (RO) in rodents,
      suggesting that compound 3 has a unique in vivo profile. Collectively, our data
      support further investigation of dual D3R and D2R antagonists for the treatment
      of drug addiction.

PMID- 27715008
TI  - Greatly Increasing Trapped Ion Populations for Mobility Separations Using
      Traveling Waves in Structures for Lossless Ion Manipulations.
AB  - The initial use of traveling waves (TW) for ion mobility (IM) separations using
      structures for lossless ion manipulations (SLIM) employed an ion funnel trap
      (IFT) to accumulate ions from a continuous electrospray ionization source and was
      limited to injected ion populations of ~106 charges due to the onset of space
      charge effects in the trapping region. Additional limitations arise due to the
      loss of resolution for the injection of ions over longer periods, such as in
      extended pulses. In this work a new SLIM "flat funnel" (FF) module has been
      developed and demonstrated to enable the accumulation of much larger ion
      populations and their injection for IM separations. Ion current measurements
      indicate a capacity of ~3.2 * 108 charges for the extended trapping volume, over
      an order of magnitude greater than that of the IFT. The orthogonal ion injection
      into a funnel shaped separation region can greatly reduce space charge effects
      during the initial IM separation stage, and the gradually reduced width of the
      path allows the ion packet to be increasingly compressed in the lateral dimension
      as the separation progresses, allowing efficient transmission through conductance
      limits or compatibility with subsequent ion manipulations. This work examined the
      TW, rf, and dc confining field SLIM parameters involved in ion accumulation,
      injection, transmission, and IM separation in the FF module using both direct ion
      current and MS measurements. Wide m/z range ion transmission is demonstrated,
      along with significant increases in the signal-to-noise ratios (S/N) due to the
      larger ion populations injected. Additionally, we observed a reduction in the
      chemical background, which was attributed to more efficient desolvation of
      solvent related clusters over the extended ion accumulation periods. The TW SLIM
      FF IM module is anticipated to be especially effective as a front end for long
      path SLIM IM separation modules.

PMID- 27715009
TI  - Crystal Structure of Os79 (Os04g0206600) from Oryza sativa: A UDP
      glucosyltransferase Involved in the Detoxification of Deoxynivalenol.
AB  - Fusarium head blight is a plant disease with significant agricultural and health
      impact which affects cereal crops such as wheat, barley, and maize and is
      characterized by reduced grain yield and the accumulation of trichothecene
      mycotoxins such as deoxynivalenol (DON). Studies have identified trichothecene
      production as a virulence factor in Fusarium graminearum and have linked DON
      resistance to the ability to form DON-3-O-glucoside in wheat. Here, the
      structures of a deoxynivalenol:UDP-glucosyltransferase (Os79) from Oryza sativa
      are reported in complex with UDP in an open conformation, in complex with UDP in
      a closed conformation, and in complex with UDP-2-fluoro-2-deoxy-d-glucose and
      trichothecene at 1.8, 2.3, and 2.2 A resolution, respectively. The active site of
      Os79 lies in a groove between the N-terminal acceptor and the C-terminal donor
      binding domains. Structural alignments reveal that Os79 likely utilizes a
      catalytic mechanism similar to those of other plant UGTs, with His 27 activating
      the trichothecene O3 hydroxyl for nucleophilic attack at C1' of the UDP-glucose
      donor. Kinetic analysis of mutant Os79 revealed that Thr 291 plays a critical
      role in catalysis as a catalytic acid or to position the UDP moiety during the
      nucleophilic attack. Steady-state kinetic analysis demonstrated that Os79
      conjugates multiple trichothecene substrates such as DON, nivalenol,
      isotrichodermol, and HT-2 toxin, but not T-2 toxin. These data establish a
      foundation for understanding substrate specificity and activity in this enzyme
      and can be used to guide future efforts to increase DON resistance in cereal
      crops.

PMID- 27715011
TI  - Optimization of Surface-Enhanced Raman Spectroscopy Conditions for Implementation
      into a Microfluidic Device for Drug Detection.
AB  - A microfluidic device is being developed by University of California-Santa
      Barbara as part of a joint effort with the United States Army to develop a
      portable, rapid drug detection device. Surface-enhanced Raman spectroscopy (SERS)
      is used to provide a sensitive, selective detection technique within the
      microfluidic platform employing metallic nanoparticles as the SERS medium. Using
      several illicit drugs as analytes, the work presented here describes the efforts
      of the Edgewood Chemical Biological Center to optimize the microfluidic platform
      by investigating the role of nanoparticle material, nanoparticle size, excitation
      wavelength, and capping agents on the performance, and drug concentration
      detection limits achievable with Ag and Au nanoparticles that will ultimately be
      incorporated into the final design. This study is particularly important as it
      lays out a systematic comparison of limits of detection and potential
      interferences from working with several nanoparticle capping agents-such as
      tannate, citrate, and borate-which does not seem to have been done previously as
      the majority of studies only concentrate on citrate as the capping agent.
      Morphine, cocaine, and methamphetamine were chosen as test analytes for this
      study and were observed to have limits of detection (LOD) in the range of (1.5
      4.7) * 10-8 M (4.5-13 ng/mL), with the borate capping agent having the best
      performance.

PMID- 27715010
TI  - Combined Measurement of 6 Fat-Soluble Vitamins and 26 Water-Soluble Functional
      Vitamin Markers and Amino Acids in 50 MUL of Serum or Plasma by High-Throughput
      Mass Spectrometry.
AB  - Targeted metabolic profiling characterized by complementary platforms,
      multiplexing and low volume consumption are increasingly used for studies using
      biobank material. Using liquid-liquid extraction, we developed a sample workup
      suitable for quantification of 6 fat- and 26 water-soluble biomarkers. 50 MUL of
      serum/plasma was mixed with dithioerythritol, ethanol, and isooctane/chloroform.
      The organic layer was used for analysis of the fat-soluble vitamins all-trans
      retinol (A), 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, alpha-tocopherol (E),
      gamma-tocopherol (E), and phylloquinone (K1) by LC-MS/MS. The remaining aqueous
      fraction was mixed with ethanol, water, pyridine, and methylchloroformate (in
      toluene) to derivatize the water-soluble biomarkers. The resulting toluene layer
      was used for GC-MS/MS analysis of alanine, alpha-ketoglutarate, asparagine,
      aspartic acid, cystathionine, total cysteine, glutamic acid, glutamine, glycine,
      histidine, total homocysteine, isoleucine, kynurenine, leucine, lysine,
      methionine, methylmalonic acid, ornithine, phenylalanine, proline, sarcosine,
      serine, threonine, tryptophan, tyrosine, and valine. Isotope-labeled internal
      standards were used for all analytes. Chromatographic run times for the LC-MS/MS
      and GC-MS/MS were 4.5 and 11 min, respectively. The limits of detection (LOD) for
      the low-concentration analytes (25-hydroxyvitamin D2, 25-hydroxyvitamin D3, and
      phylloquinone) were 25, 17, and 0.33 nM, respectively, while all other analytes
      demonstrated sensitivity significantly lower than endogenous concentrations.
      Recoveries ranged from 85.5-109.9% and within- and between-day coefficients of
      variance (CVs) were 0.7-9.4% and 1.1-17.5%, respectively. This low-volume, high
      throughput multianalyte assay is currently in use in our laboratory for
      quantification of 32 serum/plasma biomarkers in epidemiological studies.

PMID- 27715012
TI  - Anaerobic Disposal of Arsenic-Bearing Wastes Results in Low Microbially Mediated
      Arsenic Volatilization.
AB  - The removal of arsenic from drinking water sources produces arsenic-bearing
      wastes, which are disposed of in a variety of ways. Several disposal options
      involve anaerobic environments, including mixing arsenic waste with cow dung,
      landfills, anaerobic digesters, and pond sediments. Though poorly understood, the
      production of gaseous arsenic species in these environments can be a primary goal
      (cow dung mixing) or an unintended consequence (anaerobic digesters). Once
      formed, these gaseous arsenic species are readily diluted in the atmosphere.
      Arsenic volatilization can be mediated by the enzyme arsenite S
      adenosylmethionine methyltransferase (ArsM) or through the enzymes involved in
      methanogenesis. In this study, methanogenic mesocosms with arsenic-bearing ferric
      iron waste from an electrocoagulation drinking water treatment system were used
      to evaluate the role of methanogenesis in arsenic volatilization using methanogen
      inhibitors. Arsenic volatilization was highest in methanogenic mesocosms, but
      represented <0.02% of the total arsenic added. 16S rRNA cDNA sequencing, qPCR of
      mcrA transcripts, and functional gene array-based analysis of arsM expression,
      revealed that arsenic volatilization correlated with methanogenic activity.
      Aqueous arsenic concentrations increased in all mesocosms, indicating that
      unintended contamination may result from disposal in anaerobic environments. This
      highlights that more research is needed before recommending anaerobic disposal
      intended to promote arsenic volatilization.

PMID- 27715013
TI  - Functionalization of Ultrabithorax Materials with Vascular Endothelial Growth
      Factor Enhances Angiogenic Activity.
AB  - Successful design of tissue engineering scaffolds must include the ability to
      stimulate vascular development by incorporating angiogenic growth factors.
      Current approaches can allow diffusion of growth factors, incorporate active
      factors randomly, or can leave residual toxins. We addressed these problems by
      genetically fusing the gene encoding Vascular Endothelial Growth Factor (VEGF)
      with the Ultrabithorax (Ubx) gene to produce fusion proteins capable of self
      assembly into materials. We demonstrate that VEGF-Ubx materials enhance human
      endothelial cell migration, prolong cell survival, and dose-dependently activate
      the VEGF signaling pathway. VEGF-Ubx fibers attract outgrowing sprouts in an
      aortic ring assay and induce vessel formation in a chicken embryo chorioallantoic
      membrane (CAM) assay. Collectively, these results demonstrate that the activity
      of VEGF remains intact in Ubx materials. This approach could provide an
      inexpensive and facile mechanism to stimulate and pattern angiogenesis.

PMID- 27715014
TI  - Ratiometric Fluorescent Biosensing of Hydrogen Peroxide and Hydroxyl Radical in
      Living Cells with Lysozyme-Silver Nanoclusters: Lysozyme as Stabilizing Ligand
      and Fluorescence Signal Unit.
AB  - Construction of facile ratiometric fluorescent probes which possess sensitive and
      selective sensing ability for bioactive small molecules is highly desirable and
      challenging. Herein, silver nanoclusters capped with denatured lysozyme (dLys
      AgNCs) were synthesized and proved to be dual emissive. The facility of the dLys
      AgNCs ratiometric probe was attributed to the finding that the lysozyme acted not
      only as stabilizing ligand but also as fluorescence signal unit. In the presence
      of Fenton reagents, the emission of dLys-AgNCs at 640 nm was quenched by *OH,
      whereas the emission at 450 was enhanced due to *OH-induced oxidation of tyrosine
      in the lysozyme. This probe could be used for highly sensitive detection of H2O2.
      The fluorescence changes of F450/F640 had fantastic linearity to H2O2
      concentrations in the range of 0.8-200 MUmol/L (R2 = 0.9993), with a limit of
      detection (LOD) as low as 0.2 MUmol/L. Additionally, this probe was also applied
      to H2O2-generated oxidase-based biosensing. As a proof-of-concept, glucose and
      acetylcholine chloride were detected with benefical LOD values of 0.6 MUmol/L and
      0.8 MUmol/L, respectively. Furthermore, fluorescence confocal imaging
      demonstrated dLys-AgNCs had a sensitive response to fluctuation of *OH levels in
      living cells, which might have promising application in study of *OH-induced
      oxidative damage to proteins.

PMID- 27715015
TI  - Enhancement of Compound Selectivity Using a Radio Frequency Ion-Funnel Proton
      Transfer Reaction Mass Spectrometer: Improved Specificity for Explosive
      Compounds.
AB  - A key issue with any analytical system based on mass spectrometry with no initial
      separation of compounds is to have a high level of confidence in chemical
      assignment. This is particularly true for areas of security, such as airports,
      and recent terrorist attacks have highlighted the need for reliable analytical
      instrumentation. Proton transfer reaction mass spectrometry is a useful
      technology for these purposes because the chances of false positives are small
      owing to the use of a mass spectrometric analysis. However, the detection of an
      ion at a given m/z for an explosive does not guarantee that that explosive is
      present. There is still some ambiguity associated with any chemical assignment
      owing to the presence of isobaric compounds and, depending on mass resolution,
      ions with the same nominal m/z. In this article we describe how for the first
      time the use of a radio frequency ion-funnel (RFIF) in the reaction region (drift
      tube) of a proton transfer reaction-time-of-flight-mass spectrometer (PTR-ToF-MS)
      can be used to enhance specificity by manipulating the ion-molecule chemistry
      through collisional induced processes. Results for trinitrotoluene,
      dinitrotoluenes, and nitrotoluenes are presented to demonstrate the advantages of
      this new RFIF-PTR-ToF-MS for analytical chemical purposes.

PMID- 27715016
TI  - Differential Mobility Spectrometry for Inorganic Filtration in Nuclear Forensics.
AB  - Differential mobility spectrometry (DMS) is applied to the analysis of inorganic
      mixtures relevant to nuclear forensics. Three primary components of potential
      radiological dispersal devices (RDDs), cobalt, cesium, and strontium, were
      studied by DMS to demonstrate rapid sample cleanup when coupled to mass
      spectrometry. Nanosprayed salt solutions comprised of stable analogs, as proxies
      to these radioisotopes, and isobaric interferents were introduced to DMS. The DMS
      effluent was directly coupled to a mass spectrometer to confirm the elemental
      identity of the separated clusters. DMS dispersion plots demonstrated distinctive
      elemental separation from both atomic and molecular interferents. These results
      support the potential use of DMS as a means of rapid separation for inorganic
      analyses prior to analysis in a field portable mass spectrometer. The mechanism
      for this process is speculated to involve dynamics of solvent cluster formation
      under the influence of the alternating high and low electric fields of the DMS.

PMID- 27715017
TI  - Radiosynthesis and Preclinical Evaluation of 18F-Fluoroglycosylated Octreotate
      for Somatostatin Receptor Imaging.
AB  - Short synthetic octapeptide analogs derived from the native somatostatin peptides
      SST-14 and SST-28, namely, octreotate (TATE) or octreotide (TOC), bind with high
      affinity to somatostatin receptors (sstr), mainly to subtypes 2 and 5, which are
      expressed in high density on neuroendocrine tumors (NET). Therefore, radiolabeled
      TATE or TOC derivatives represent highly valuable imaging probes for NET
      diagnosis by positron emission tomography (PET). The aim of our study was the
      development of an 18F-labeled octreotate analog as an alternative radiotracer for
      the clinically established 68Ga-DOTATOC and 68Ga-DOTATATE. We applied our
      previously developed method based on copper(I)-catalyzed azide-alkyne
      cycloaddition (CuAAC) to the radiosynthesis of 18F-fluoroglycosylated TATE
      ([18F]FGlc-TATE). [18F]FGlc-TATE was obtained in high yields of 19-22% (non-decay
      corrected, referred to [18F]fluoride) and in high specific activities of 32-106
      GBq/MUmol. [18F]FGlc-TATE showed high affinity to sstr expressed on AR42J cells
      (IC50 = 4.2 nM) with fast and high internalization, and a beneficial logD7.4 of 
      1.8. In AR42J tumor bearing nude mice, [18F]FGlc-TATE showed high and specific
      tumor uptake of 5.6%ID/g at 60 min post-injection, as determined by blocking
      experiments using octreotide, and fast clearance from other organs, resulting in
      excellent tumor-to-blood ratios increasing from 9 to 17 from 30 to 60 min post
      injection. Small animal PET studies revealed high uptake of [18F]FGlc-TATE in the
      tumor which could be blocked with octreotide by >99%. Overall, [18F]FGlc-TATE
      revealed excellent in vitro and in vivo properties and is therefore a viable
      alternative 18F-labeled radiopeptide for imaging somatostatin receptor-positive
      tumors by PET.

PMID- 27715018
TI  - Mechanistic Design of Chemically Diverse Polymers with Applications in Oral Drug
      Delivery.
AB  - Polymers play a key role in stabilizing amorphous drug formulations, a recent
      strategy employed to improve solubility and bioavailability of drugs delivered
      orally. However, the molecular mechanism of stabilization is unclear, therefore,
      the rational design of new crystallization-inhibiting excipients remains a
      substantial challenge. This article presents a combined experimental and
      computational approach to elucidate the molecular features that improve the
      effectiveness of cellulose polymers as solution crystallization inhibitors, a
      crucial first step toward their rational design. Polymers with chemically diverse
      substituents including carboxylic acids, esters, ethers, alcohols, amides,
      amines, and sulfides were synthesized. Measurements of nucleation induction times
      of the model drug, telaprevir, show that the only effective polymers contained
      carboxylate groups in combination with an optimal hydrocarbon chain length.
      Computational results indicate that polymer conformation as well as solvation
      free energy are important determinants of effectiveness at inhibiting
      crystallization and show that simulations are a promising predictive tool in the
      screening of polymers. This study suggests that polymers need to have an adequate
      hydrophilicity to promote solvation in an aqueous environment, and sufficient
      hydrophobic regions to drive interactions with the drug. Particularly, the right
      balance between key substituent groups and lengths of hydrocarbon side chains is
      needed to create effective materials.

PMID- 27715019
TI  - Land Use in LCA: Including Regionally Altered Precipitation to Quantify Ecosystem
      Damage.
AB  - The incorporation of soil moisture regenerated by precipitation, or green water,
      into life cycle assessment has been of growing interest given the global
      importance of this resource for terrestrial ecosystems and food production. This
      paper proposes a new impact assessment model to relate land and water use in
      seasonally dry, semiarid, and arid regions where precipitation and
      evapotranspiration are closely coupled. We introduce the Precipitation Reduction
      Potential midpoint impact representing the change in downwind precipitation as a
      result of a land transformation and occupation activity. Then, our end-point
      impact model quantifies terrestrial ecosystem damage as a function of
      precipitation loss using a relationship between woody plant species richness,
      water and energy regimes. We then apply the midpoint and end-point models to the
      production of soybean in Southeastern Amazonia which has resulted from the
      expansion of cropland into tropical forest, with noted effects on local
      precipitation. Our proposed cause-effect chain represents a complementary
      approach to previous contributions which have focused on water consumption
      impacts and/or have represented evapotranspiration as a loss to the water cycle.

PMID- 27715020
TI  - Marine Phages As Tracers: Effects of Size, Morphology, and Physico-Chemical
      Surface Properties on Transport in a Porous Medium.
AB  - Although several studies examined the transport of viruses in terrestrial systems
      only few studies exist on the use of marine phages (i.e., nonterrestrial viruses
      infecting marine host bacteria) as sensitively detectable microbial tracers for
      subsurface colloid transport and water flow. Here, we systematically quantified
      and compared for the first time the effects of size, morphology and
      physicochemical surface properties of six marine phages and two coliphages (MS2,
      T4) on transport in sand-filled percolated columns. Phage-sand interactions were
      described by colloidal filtration theory and the extended Derjaguin-Landau-Verwey
      Overbeek approach (XDLVO), respectively. The phages belonged to different
      families and comprised four phages never used in transport studies (i.e., PSA
      HM1, PSA-HP1, PSA-HS2, and H3/49). Phage transport was influenced by size,
      morphology and hydrophobicity in an approximate order of size > hydrophobicity >=
      morphology. Two phages PSA-HP1, PSA-HS2 (Podoviridae and Siphoviridae) exhibited
      similar mass recovery as commonly used coliphage MS2 and were 7-fold better
      transported than known marine phage vB_PSPS-H40/1. Differing properties of the
      marine phages may be used to trace transport of indigenous viruses, natural
      colloids or anthropogenic nanomaterials and, hence, contribute to better risk
      analysis. Our results underpin the potential role of marine phages as microbial
      tracer for transport of colloidal particles and water flow.

PMID- 27715021
TI  - Characterization of Endogenous and Reduced Promoters for Oxygen-Limited Processes
      Using Escherichia coli.
AB  - Oxygen limitation can be used as a simple environmental inducer for the
      expression of target genes. However, there is scarce information on the
      characteristics of microaerobic promoters potentially useful for cell engineering
      and synthetic biology applications. Here, we characterized the Vitreoscilla
      hemoglobin promoter (Pvgb) and a set of microaerobic endogenous promoters in
      Escherichia coli. Oxygen-limited cultures at different maximum oxygen transfer
      rates were carried out. The FMN-binding fluorescent protein (FbFP), which is a
      nonoxygen dependent marker protein, was used as a reporter. Fluorescence and
      fluorescence emission rates under oxygen-limited conditions were the highest when
      FbFP was under transcriptional control of PadhE, Ppfl and Pvgb. The lengths of
      the E. coli endogenous promoters were shortened by 60%, maintaining their key
      regulatory elements. This resulted in improved promoter activity in most cases,
      particularly for PadhE, Ppfl and PnarK. Selected promoters were also evaluated
      using an engineered E. coli strain expressing Vitreoscilla hemoglobin (VHb). The
      presence of the VHb resulted in a better repression using these promoters under
      aerobic conditions, and increased the specific growth and fluorescence emission
      rates under oxygen-limited conditions. These results are useful for the selection
      of promoters for specific applications and for the design of modified artificial
      promoters.

PMID- 27715023
TI  - Correction to "Product Selectivity Controlled by Zeolite Crystals in Biomass
      Hydrogenation over a Palladium Catalyst".

PMID- 27715022
TI  - Including Bioconcentration Kinetics for the Prioritization and Interpretation of
      Regulatory Aquatic Toxicity Tests of Highly Hydrophobic Chemicals.
AB  - Worldwide, regulations of chemicals require short-term toxicity data for
      evaluating hazards and risks of the chemicals. Current data requirements on the
      registration of chemicals are primarily based on tonnage and do not yet consider
      properties of chemicals. For example, short-term ecotoxicity data are required
      for chemicals with production volume greater than 1 or 10 ton/y according to
      REACH, without considering chemical properties. Highly hydrophobic chemicals are
      characterized by low water solubility and slow bioconcentration kinetics, which
      may hamper the interpretation of short-term toxicity experiments. In this work,
      internal concentrations of highly hydrophobic chemicals were predicted for
      standard acute ecotoxicity tests at three trophic levels, algae, invertebrate,
      and fish. As demonstrated by comparison with maximum aqueous concentrations at
      water solubility, chemicals with an octanol-water partition coefficient (Kow)
      greater than 106 are not expected to reach sufficiently high internal
      concentrations for exerting effects within the test duration of acute tests with
      fish and invertebrates, even though they might be intrinsically toxic. This
      toxicity cutoff was explained by the slow uptake, i.e., by kinetics, not by
      thermodynamic limitations. Predictions were confirmed by data entries of the
      OECD's screening information data set (SIDS) (n = 746), apart from a few
      exceptions concerning mainly organometallic substances and those with
      inconsistency between water solubility and Kow. Taking error propagation and
      model assumptions into account, we thus propose a revision of data requirements
      for highly hydrophobic chemicals with log Kow > 7.4: Short-term toxicity tests
      can be limited to algae that generally have the highest uptake rate constants,
      whereas the primary focus of the assessment should be on persistence,
      bioaccumulation, and long-term effects.

PMID- 27715024
TI  - Synthesis and Characterization of Chlorpyrifos/Copper(II) Schiff Base Mesoporous
      Silica with pH Sensitivity for Pesticide Sustained Release.
AB  - The salicylaldehyde-modified mesoporous silica (SA-MCM-41) was prepared through a
      co-condensation method. Through the bridge effect from the copper ion, which also
      acts as the nutrition of the plant, the model drug chlorpyrifos (CH) was
      supported on the copper(II) Schiff base mesoporous silica (Cu-MCM-41) to form a
      highly efficient sustained-release system (CH-Cu-MCM-41) for pesticide delivery.
      The experimental results showed that the larger the concentration of the copper
      ion, the more adsorption capacity (AC) of Cu-MCM-41 for chlorpyrifos and the
      smaller its release rate. The results confirmed the existence of a coordination
      bond between SA-MCM-41 and copper ions as well as a coordination bond between Cu
      MCM-41 and chlorpyrifos. The AC of SA-MCM-41 is 106 mg/g, while that of Cu-MCM-41
      is 295 mg/g. The as-synthesized system showed significant pH sensitivity. Under
      the condition of pH <= 7, the release rate of chlorpyrifos decreased with
      increasing pH, whereas its release rate in weak base conditions was slightly
      larger than that in weak acid conditions. Meanwhile, the drug release rate of the
      as-synthesized system was also affected by the temperature. Their sustained
      release curves can be described by the Korsmeyer-Peppas equation.

PMID- 27715025
TI  - Ethylenediamine-Assisted Hydrothermal Synthesis of NaCaSiO3OH: Controlled
      Morphology, Mechanism, and Luminescence Properties by Doping Eu3+/Tb3.
AB  - This paper demonstrates a facile hydrothermal method using ethylenediamine (EDA)
      as a "shape modifier" for the controlled synthesis of rod bunch, decanedron,
      spindle, flakiness, and flowerlike NaCaSiO3OH microarchitectures. The set of
      experimental conditions is important to obtain adjustable shape and size of
      NaCaSiO3OH particles, as the change in either the amount of EDA/H2O or reaction
      time, or the amount of NaOH. Accordingly, the crystal growth mechanism during the
      synthesis process is proposed, and it is found that the EDA, acting as the
      chelating agent and shape modifier, plays a crucial role in fine-tuning the
      NaCaSiO3OH morphology. Morphology evolution process of flowerlike NaCaSiO3OH as a
      function of NaOH is also explained in detail. Eu3+/Tb3+ doped NaCaSiO3OH samples
      exhibit strong red and green emission under ultraviolet excitation, corresponding
      to the characteristic electronic transitions of Eu3+ and Tb3+. These results
      imply that the morphology-tunable NaCaSiO3OH:Eu3+/Tb3+ microarchitectures with
      tunable luminescence properties are expected to have promising applications for
      micro/nano optical functional devices.

PMID- 27715027
TI  - Synthesis of a doubly interlocked [2]-catenane.

PMID- 27715028
TI  - A molecular shuttle.

PMID- 27715026
TI  - Therapeutic Delivery of H2S via COS: Small Molecule and Polymeric Donors with
      Benign Byproducts.
AB  - Carbonyl sulfide (COS) is a gas that may play important roles in mammalian and
      bacterial biology, but its study is limited by a lack of suitable donor
      molecules. We report here the use of N-thiocarboxyanhydrides (NTAs) as COS donors
      that release the gas in a sustained manner under biologically relevant conditions
      with innocuous peptide byproducts. Carbonic anhydrase converts COS into H2S,
      allowing NTAs to serve as either COS or H2S donors, depending on the availability
      of the enzyme. Analysis of the pseudo-first-order H2S release rate under
      biologically relevant conditions revealed a release half-life of 75 min for the
      small molecule NTA under investigation. A polynorbornene bearing pendant NTAs
      made by ring-opening metathesis polymerization was also synthesized to generate a
      polymeric COS/H2S donor. A half-life of 280 min was measured for the polymeric
      donor. Endothelial cell proliferation studies revealed an enhanced rate of
      proliferation for cells treated with the NTA over untreated controls.

PMID- 27715029
TI  - Investigation of the Impact of Different Terms in the Second Order Hamiltonian on
      Excitation Energies of Valence and Rydberg States.
AB  - Describing electronically excited states of molecules accurately poses a
      challenging problem for theoretical methods. Popular second order techniques like
      Linear Response CC2 (CC2-LR), Partitioned Equation-of-Motion MBPT(2) (P-EOM
      MBPT(2)), or Equation-of-Motion CCSD(2) (EOM-CCSD(2)) often produce results that
      are controversial and are ill-balanced with their accuracy on valence and Rydberg
      type states. In this study, we connect the theory of these methods and, to
      investigate the origin of their different behavior, establish a series of
      intermediate variants. The accuracy of these on excitation energies of singlet
      valence and Rydberg electronic states is benchmarked on a large sample against
      high-accuracy Linear Response CC3 references. The results reveal the role of
      individual terms of the second order similarity transformed Hamiltonian, and the
      reason for the bad performance of CC2-LR in the description of Rydberg states. We
      also clarify the importance of the T1 transformation employed in the CC2
      procedure, which is found to be very small for vertical excitation energies.

PMID- 27715030
TI  - Electrochemically and Photochemically Driven Ring Motions in a Disymmetrical
      Copper [2]-Catenate.
AB  - By applying the three-dimensional template effect of copper(I), previously used
      for making various interlocking ring systems, a new disymmetrical [2]-catenate
      has been made which consists of two different interlocking rings. One ring
      contains a 2,9-diphenyl-1,10-phenanthroline (dpp) unit whereas the other cycle
      incorporates both a dpp motif and a 2,2',6',2''-terpyridine (terpy) fragment, the
      coordination site of these two chelates pointing toward the inside of the ring.
      Depending on the oxidation state of the central metal (Cu(I) or Cu(II)), and thus
      on its preferred coordination number, two distinct situations have been observed.
      With monovalent copper, the two dpp units interact with the metal and the terpy
      fragment remains free, at the outside of the molecule. By contrast, when the
      catenate is complexed to divalent copper, the terpy motif is bonded to the metal
      and it is now a dpp ligand which lies at the periphery of the complex. This dual
      coordination mode leads to dramatically different molecular shapes and properties
      for both forms. The molecular motion which interconverts the four- and the five
      coordinate complexes can be triggered chemically, electrochemically, or
      photochemically by changing the oxidation state of the copper center (II/I). The
      process has been studied by electrochemistry and by UV-vis spectroscopy.
      Interestingly, once the stable 4-coordinate copper(I) complex has been oxidized
      to a thermodynamically unstable pseudo-tetrahedral copper(II) species, the rate
      of the gliding motion of the rings which will afford the stable 5-coordinate
      species (copper(II) coordinated to dpp and terpy) can be controlled at will.
      Under certain experimental conditions, the changeover process is extremely slow
      (weeks), and the 4-coordinate complex is more or less frozen. By contrast,
      addition of a coordinating counterion to the medium (Cl-) enormously speeds up
      the rearrangement and leads to the thermodynamically stable 5-coordinate complex
      within minutes.

PMID- 27715031
TI  - Synthesis and Isomeric Analysis of RuII Complexes Bearing Pentadentate Scaffolds.
AB  - A RuII-pentadentate polypyridyl complex [RuII(kappa-N5-bpy2PYMe)Cl]+ (1+,
      bpy2PYMe = 1-(2-pyridyl)-1,1-bis(6-2,2'-bipyridyl)ethane) and its aqua derivative
      [RuII(kappa-N5-bpy2PYMe)(H2O)]2+ (22+) were synthesized and characterized by
      experimental and computational methods. In MeOH, 1+ exists as two isomers in
      different proportions, cis (70%) and trans (30%), which are interconverted under
      thermal and photochemical conditions by a sequence of processes: chlorido
      decoordination, decoordination/recoordination of a pyridyl group, and chlorido
      recoordination. Under oxidative conditions in dichloromethane, trans-12+
      generates a [RuIII(kappa-N4-bpy2PYMe)Cl2]+ intermediate after the exchange of a
      pyridyl ligand by a Cl- counterion, which explains the trans/cis isomerization
      observed when the system is taken back to Ru(II). On the contrary, cis-12+ is in
      direct equilibrium with trans-12+, with absence of the kappa-N4-bis-chlorido
      RuIII-intermediate. All these equilibria were modeled by density functional
      theory calculations. Interestingly, the aqua derivative is obtained as a pure
      trans-[RuII(kappa-N5-bpy2PYMe)(H2O)]2+ isomer (trans-22+), while the addition of
      a methyl substituent to a single bpy of the pentadentate ligand leads to the
      formation of a single cis isomer for both chlorido and aqua derivatives
      [RuII(kappa-N5-bpy(bpyMe)PYMe)Cl]+ (3+) and [RuII(kappa-N5
      bpy(bpyMe)PYMe)(H2O)]2+ (42+) due to the steric constraints imposed by the
      modified ligand. This system was also structurally and electrochemically compared
      to the previously reported [RuII(PY5Me2)X]n+ system (X = Cl, n = 1 (5+); X = H2O,
      n = 2 (62+)), which also contains a kappa-N5-RuII coordination environment, and
      to the newly synthesized [RuII(PY4Im)X]n+ complexes (X = Cl, n = 1 (7+); X = H2O,
      n = 2 (82+)), which possess an electron-rich kappa-N4C-RuII site due to the
      replacement of a pyridyl group by an imidazolic carbene.

PMID- 27715033
TI  - Electrochemically Triggered Swinging of a [2]-Catenate.

PMID- 27715032
TI  - Encapsulation of Biological and Chemical Agents for Plant Nutrition and
      Protection: Chitosan/Alginate Microcapsules Loaded with Copper Cations and
      Trichoderma viride.
AB  - Novel chitosan/alginate microcapsules simultaneously loaded with copper cations
      and Trichoderma viride have been prepared and characterized. Information about
      the intermolecular interactions between biopolymers and bioactive agents was
      obtained by Fourier transform infrared spectroscopy. Encapsulation of T. viride
      spores and the presence of copper cations in the same compartment does not
      inhibit their activity. Microcapsule loading capacity and efficiency as well as
      swelling behavior and release depend on both the size of the microcapsule and
      bioactive agents. The in vitro copper cation release profile was fitted to a
      Korsmeyer-Peppas empirical model. Fickian diffusion was found to be a rate
      controlling mechanism of release from smaller microcapsules, whereas anomalous
      transport kinetics controlled release from larger microcapsules. The T. viride
      spore release profile exhibited exponential release over the initial lag time.
      The results obtained opened perspectives for the future use of chitosan/alginate
      microcapsules simultaneously loaded with biological and chemical agents in plant
      nutrition and protection.

PMID- 27715034
TI  - A Switchable Hybrid [2]-Catenane Based on Transition Metal Complexation and pi
      Electron Donor-Acceptor Interactions.
AB  - A bimodal [2]-catenane has been synthesized via a copper(I) templated synthesis.
      The compound contains both a transition metal coordination site and a set of pi
      electron rich and pi-electron deficient aromatic units suitable for the formation
      of acceptor-donor complexes. Each constituent ring is thus different from the
      other, and the organic backbone can adopt two favored contrasting orientations by
      circumrotation of one ring within the other:  (i) in the metal complex mode, each
      dpp unit (dpp = 2,9-diphenyl-1,10-phenanthroline) is entwined about the other,
      while a cationic species is complexed in the coordination site thus created; (ii)
      in the organic pi-electron acceptor-donor complex mode, the dpp fragments are
      remote from one another, and the pi-electron rich and pi-electron deficient units
      stack to form a complex. The conversion of one binding mode to the other implies
      complete topographical rearrangement of the molecule. It can be triggered by
      adding or removing the cation center (Cu+, Li+, or H+), bonded to the dpp
      containing complexing site. Interestingly, this switching process can be easily
      monitored by 1H NMR, since it involves drastic relative orientational changes. It
      can also be evidenced by electronic spectroscopy. In particular, the proton
      driven rearrangement reactions lead to significant changes in the absorption
      spectrum, which correspond to the appearance (by deprotonation) and disappearance
      (by protonation of the dpp) of a charge transfer band (around 470 nm) resulting
      from the pi-electron donor-acceptor noncovalent interaction.

PMID- 27715035
TI  - Benchmarking Post-Hartree-Fock Methods To Describe the Nonlinear Optical
      Properties of Polymethines: An Investigation of the Accuracy of Algebraic
      Diagrammatic Construction (ADC) Approaches.
AB  - Third-order nonlinear optical (NLO) properties of polymethine dyes have been
      widely studied for applications such as all-optical switching. However, the
      limited accuracy of the current computational methodologies has prevented a
      comprehensive understanding of the nature of the lowest excited states and their
      influence on the molecular optical and NLO properties. Here, attention is paid to
      the lowest excited-state energies and their energetic ratio, as these
      characteristics impact the figure-of-merit for all-optical switching. For a
      series of model polymethines, we compare several algebraic diagrammatic
      construction (ADC) schemes for the polarization propagator with approximate
      second-order coupled cluster (CC2) theory, the widely used INDO/MRDCI approach
      and the symmetry-adapted cluster configuration interaction (SAC-CI) algorithm
      incorporating singles and doubles linked excitation operators (SAC-CI SD-R). We
      focus in particular on the ground-to-excited state transition dipole moments and
      the corresponding state dipole moments, since these quantities are found to be of
      utmost importance for an effective description of the third-order polarizability
      gamma and two-photon absorption spectra. A sum-overstates expression has been
      used, which is found to quickly converge. While ADC(3/2) has been found to be the
      most appropriate method to calculate these properties, CC2 performs poorly.

PMID- 27715036
TI  - An Efficient, Augmented Surface Hopping Algorithm That Includes Decoherence for
      Use in Large-Scale Simulations.
AB  - We propose and implement a highly efficient augmented surface hopping algorithm
      that (i) can be used for large simulations (with many nuclei and many electronic
      states) and (ii) includes the effects of decoherence without parametrization. Our
      protocol is based on three key modifications of the surface hopping methodology:
      (a) a novel separation of classical and quantum degrees of freedom that treats
      avoided and trivial crossings efficiently, (b) a multidimensional approximation
      of the time derivative matrix that avoids explicit construction of the derivative
      coupling at most time steps, and (c) an efficient approximation for the augmented
      fewest-switches surface hopping decoherence rate. We will show that this protocol
      can be several orders of magnitude more efficient than the traditional protocol
      for large multidimensional problems. Furthermore, the marginal cost for including
      decoherence effects is now negligible.

PMID- 27715037
TI  - Synthesis of biscopper(I) [3]-catenates: multiring interlocked coordinating
      systems.

PMID- 27715038
TI  - Designing Multifunctional 5-Cyanoisophthalate-Based Coordination Polymers as
      Single-Molecule Magnets, Adsorbents, and Luminescent Materials.
AB  - Detailed structural, magnetic, and photoluminescence characterization of a family
      of new compounds based on 5-cyanoisophthalate (CNip) ligand and several
      transition metal or lanthanide ions, namely, [Cu3(MU3-CNip)2(MU-H2O)2(MU3-OH)2]n
      (1), {[Co3(MU4-CNip)3(DMF)4].~2DMF}n (2), [Cd(MU4-CNip) (DMF)]n (3), {[Ln2(MU4
      CNip)(MU3-CNip)2(DMF)4].~DMF.H2O}n (4-Ln) (with LnIII = Tb, Dy, and Er),
      {[Gd6(MU3-CNip)5(MU4-CNip)3(MU-form)2(H2O) (DMF)10].~3DMF.3H2O}n (5), {[Zn32(MU4
      CNip)12(MU-CNip)12(MU4-O)8(H2O)24].~12DMF}n (6) (where DMF = dimethylformamide,
      form = formate), is reported. The large structural diversity found in the system
      may be explained mainly in terms of the coordination characteristics that are
      inherent to the employed metal ions, the coordination versatility of the
      dicarboxylic ligand and the synthetic conditions. Interestingly, some crystal
      structures (three-dimensional (3D) frameworks of 4-Ln and 5 and 3D network of 6)
      exhibit open architectures containing large solvent-occupied void systems, among
      which 5 reveals permanent porosity as confirmed by N2 adsorption measurements at
      77 K. Magnetic direct current (dc) susceptibility data on compounds 1, 2, and 5
      were measured. Moreover, compounds 2, 4-Dy, 4-Er, and 5 show slow magnetic
      relaxation, from which it is worth highlighting the effective energy barrier of
      44 K at zero dc field for the dysprosium counterpart. Compound 5 also deserves to
      be mentioned given the few 3D Gd-organic frameworks reported examples.
      Photophysical properties were also accomplished at different temperatures,
      confirming both the fluorescent emission of 5-cyanoisophthalate ligands when
      coordinated to cadmium ions in 3 and their capacity to sensitize the long-lived
      fluorescence of the selected lanthanide ions in 4-Ln. Broken symmetry and time
      dependent density functional theory computational calculations support the
      experimental luminescence and magnetic properties.

PMID- 27715039
TI  - Probing the Effect of Axial Ligands on Easy-Plane Anisotropy of Pentagonal
      Bipyramidal Cobalt(II) Single-Ion Magnets.
AB  - We herein reported the synthetic, structural, computational, and magnetic studies
      of four air-stable heptacoordinated mononuclear cobalt(II) complexes, namely,
      [CoII(tdmmb)(H2O)2][BF4]2 (1), [CoII(tdmmb)(CN)2].2H2O (2), [CoII(tdmmb)(NCS)2]
      (3), and [CoII(tdmmb)(SPh)2] (4) (tdmmb = 1,3,10,12-tetramethyl-1,2,11,12
      tetraaza[[3](2,6)pyridino[3](2,9)-1,10-phenanthrolinophane-2,10-diene; SPh- =
      thiophenol anion). Constrained by the rigid pentadentate macrocyclic ligand
      tdmmb, the CoII centers in all of these complexes are in the heptacoordinated
      pentagonal-bipyramidal geometry. While the equatorial environments of these
      complexes remain very similar to each other, the axial ligands are systematically
      modified from C to N to O to S atoms. Analyses of the magnetic data and the ab
      initio calculations both reveal large easy-plane magnetic anisotropy (D > 0) for
      all four complexes. While the experimentally obtained D values do not show any
      clear tendency when the axial coordinated atoms change from C to N to O atoms
      (complexes 1-3), the largest value is for the heavier and softer S-atom
      coordinated complex 4. Because of significant magnetic anisotropy, all four
      complexes are field-induced single-ion magnets. This work represents a delicate
      modification of the magnetic anisotropy by tuning the chemical environment of the
      metal centers.

PMID- 27715040
TI  - Synthesis of Substituted 2,3-Benzodiazepines.
AB  - A new, four-step synthetic route for substituted 2,3-benzodiazepines 1, starting
      from aldehyde 4, was developed with excellent overall yields. This route included
      the 1,2-addition of various aromatic Grignard reagents to 4, PCC oxidation, and
      aerobic Wacker-type oxidation of the olefinic group of 6, followed by
      condensation of the resulting 1,5-dicarbonyl 7 with N2H4. Isoquinolones 9 were
      obtained when an aldehyde group was used instead of a ketone. The key structures
      were confirmed by X-ray single-crystal diffraction analysis.

PMID- 27715041
TI  - Turn: Weak Interactions and Rotational Barriers in Molecules-Insights from
      Substituted Butynes.
AB  - The nature of the bonding and a definite preference for an eclipsed geometry in
      several substituted but-2-ynes, including certain novel derivatives are uncovered
      and examined. In particular, we consider the molecular species R3C-C=C-CR3 (where
      R= H, F, Cl, Br, I, and CN), their R3C-B=N-CR3 analogues, and a few novel exo
      bridge systems with intramolecular hydrogen bonds running parallel to the C-C=C-C
      chain. In some cases, the potential energy surfaces are remarkably flat-so flat,
      in fact, that free rotation is predicted for those molecules at very low
      temperatures. A systematic investigation of the bonding in the halogenated
      butynes demonstrates that the eclipsed conformation actually becomes more stable
      relative to the staggered form as R becomes larger and less electron-withdrawing.
      The rotational barriers (the differences in energy between the eclipsed and
      staggered geometries) are magnified significantly, however, in a special case
      where selected R groups at the ends of the R3C-C=C-CR'3 molecule form hydrogen
      bonds parallel to the C-C=C-C core. In those systems, the hydrogen bonds serve as
      a weak locking mechanism that favors the eclipsed conformation. A comparison of
      HF and uncorrected DFT methods versus the MP2(full), CCSD(T), and other
      dispersion-corrected methods confirms that correlation accounts to a significant
      extent for barriers in substituted butyne compounds. In the hydrogen-bonded
      systems, the barriers are comparable to and larger in some cases than the
      barriers observed for the more extensively studied ethane molecule.

PMID- 27715042
TI  - Diastereoselective Ortho Lithiation of Phosphinimidic Amides: A Multinuclear
      Magnetic Resonance and Computational Study.
AB  - The structure of the dianion (SP,RC)-10 formed in the diastereoselective N,Cortho
      dilithiation of the phosphinimidic amide (RC)-Ph2P(?NCO2Me)NHCH(Me)Ph (5; dr of
      95:5) with tert-butyllithium in THF has been elucidated using multinuclear
      magnetic resonance methods, including 2D 7Li,nX-HMQC (nX = 15N, 31P)
      correlations. (SP,RC)-10 consists of a monomer in which C,N and N,O chelation of
      the lithium cations generates a system containing a five- and a six-membered
      metallacycle, respectively, sharing a P-N bond with the lithium atoms connected
      through the NCO moiety of the phosphazenyl group. Selective deprotonation of the
      pro-S P-phenyl ring of 5 was ascertained through NOE measurements. DFT
      computations at the M06-2X(SMD,THF)/6-311+G(d,p)//M06-2X/6-31G(d) level showed
      that the stereoselective ortho deprotonation process fulfills the features of the
      CIPE model. The P?N linkage of the N-lithiated species (RC)-8 acts as a directing
      metalation group via N...LitBu coordination. The mixed complex that is formed
      evolves to a more stabilized species due to the intramolecular coordination of
      the OMe group to the lithium cation of the base. Abstraction of the ortho proton
      proceeds with energy barriers of 12.4 and 13.3 kcal/mol for the pro-R and pro-S
      phenyl rings. The preference for the latter is explained in terms of the Curtin
      Hammett principle.

PMID- 27715043
TI  - Adsorption, Dissociation, and Dehydrogenation of Water Monomer and Water Dimer on
      the Smallest 3D Aluminum Particle. The O-H Dissociation Barrier Disappears for
      the Dimer.
AB  - We present a detailed mechanistic study on the interaction and reaction of water
      monomer and water dimer with the smallest 3D aluminum particle (Al6) by employing
      density functional and explicitly correlated coupled cluster CCSD(T)-F12
      theories. Water adsorption, dissociation, and dehydrogenation are considered. For
      the monomer reaction, where core-valence correlation and an extrapolation to the
      complete basis set limit is allowed for, our coupled cluster calculations predict
      the O-H dissociation barrier of about 2 kcal/mol. For the dimer reaction, two
      distinct reaction paths are identified, initiated by forming separate dimer
      complexes wherein (H2O)2 adsorbs mainly via the oxygen atom of the donor H2O
      molecule. The key O-H dissociation transition states of the dimer reaction
      involve a concerted migration of two H atoms resulting in the dissociation of the
      donor molecule and formation of the OH-water complex adsorbed on the metal
      cluster's surface. The most remarkable feature of both dimer reaction energy
      profiles is the lack of the overall energy barrier for the (rate-determining) O-H
      dissociation. The hydrogen bond acceptor molecule is suggested to have an extra
      catalytic effect on the O-H dissociation barrier of the hydrogen bond donor
      molecule by removing this barrier. A similar effect on the dehydrogenation step
      is indicated.

PMID- 27715044
TI  - The Activation of c-Src Tyrosine Kinase: Conformational Transition Pathway and
      Free Energy Landscape.
AB  - Tyrosine kinases are important cellular signaling allosteric enzymes that
      regulate cell growth, proliferation, metabolism, differentiation, and migration.
      Their activity must be tightly controlled, and malfunction can lead to a variety
      of diseases, particularly cancer. The nonreceptor tyrosine kinase c-Src, a
      prototypical model system and a representative member of the Src-family,
      functions as complex multidomain allosteric molecular switches comprising SH2 and
      SH3 domains modulating the activity of the catalytic domain. The broad picture of
      self-inhibition of c-Src via the SH2 and SH3 regulatory domains is well
      characterized from a structural point of view, but a detailed molecular mechanism
      understanding is nonetheless still lacking. Here, we use advanced computational
      methods based on all-atom molecular dynamics simulations with explicit solvent to
      advance our understanding of kinase activation. To elucidate the mechanism of
      regulation and self-inhibition, we have computed the pathway and the free energy
      landscapes for the "inactive-to-active" conformational transition of c-Src for
      different configurations of the SH2 and SH3 domains. Using the isolated c-Src
      catalytic domain as a baseline for comparison, it is observed that the SH2 and
      SH3 domains, depending upon their bound orientation, promote either the inactive
      or active state of the catalytic domain. The regulatory structural information
      from the SH2-SH3 tandem is allosterically transmitted via the N-terminal linker
      of the catalytic domain. Analysis of the conformational transition pathways also
      illustrates the importance of the conserved tryptophan 260 in activating c-Src,
      and reveals a series of concerted events during the activation process.

PMID- 27715045
TI  - Predicted Structures of the Proton-Bound Membrane-Embedded Rotor Rings of the
      Saccharomyces cerevisiae and Escherichia coli ATP Synthases.
AB  - Recent years have witnessed a renewed interest in the ATP synthase as a drug
      target against human pathogens. Indeed, clinical, biochemical, and structural
      data indicate that hydrophobic inhibitors targeting the membrane-embedded proton
      binding sites of the c-subunit ring could serve as last-resort antibiotics
      against multidrug resistant strains. However, because inhibition of the
      mitochondrial ATP synthase in humans is lethal, it is essential that these
      inhibitors be not only potent but also highly selective for the bacterial enzyme.
      To this end, a detailed understanding of the structure of this protein target is
      arguably instrumental. Here, we use computational methods to predict the atomic
      structures of the proton-binding sites in two prototypical c-rings: that of the
      ATP synthase from Saccharomyces cerevisiae, which is a model system for
      mitochondrial enzymes, and that from Escherichia coli, which can be pathogenic
      for humans. Our study reveals the structure of these binding sites loaded with
      protons and in the context of the membrane, that is, in the state that would
      mediate the recognition of a potential inhibitor. Both structures reflect a mode
      of proton coordination unlike those previously observed in other c-ring
      structures, whether experimental or modeled.

PMID- 27715046
TI  - Divergent Synthesis of Three Classes of Antifungal Amphiphilic Kanamycin
      Derivatives.
AB  - A concise and novel method for site-selective alkylation of 1,3,6',3"
      tetraazidokanamycin has been developed that leads to the divergent synthesis of
      three classes of kanamycin A derivatives. These new amphiphilic kanamycin
      derivatives bearing alkyl chains length of 4, 6, 7, 8, 9, 10, 12, 14, and 16 have
      been tested for their antibacterial and antifungal activities. The antibacterial
      effect of the synthesized kanamycin derivatives declines or disappears as
      compared to the original kanamycin A. Several compounds, especially those with
      octyl chain at O-4" and/or O-6" positions on the ring III of kanamycin A, show
      very strong activity as antifungal agents. In addition, these compounds display
      no toxicity toward mammalian cells. Finally, computational calculation has
      revealed possible factors that are responsible for the observed regioselectivity.
      The simplicity in chemical synthesis and the fungal specific property make the
      lead compounds ideal candidates for the development of novel antifungal agents.

PMID- 27715047
TI  - Reply to "Comment on 'Osmolyte Effects on Monoclonal Antibody Stability and
      Concentration-Dependent Protein Interactions with Water and Common Osmolytes'".

PMID- 27715048
TI  - Meroterpenoids and Chalcone-Lignoids from the Roots of Mimosa diplotricha.
AB  - Six new meroterpenoids, diplomeroterpenoids A-F (1-6), two new chalcone-lignoids,
      diplochalcolins A and B (7, 8), and 13 known compounds were isolated from the
      root extract of Mimosa diplotricha. Diplomeroterpenoids A-F consist of a 4H
      chromen-4-one and a diterpenoid unit, and their absolute configurations were
      determined by X-ray crystallographic analysis. Compounds 1-3 and 5 showed potent
      inhibitory activity on protein farnesyl transferase, with IC50 values from 5.0 to
      8.5 MUM. Compound 1 showed antiproliferative activity against human
      hepatoblastoma HepG2 cells with a GI50 value of approximately 8.6 MUM.

PMID- 27715049
TI  - In-Vial Temperature Gradient Headspace Single Drop Microextraction Designed by
      Multiphysics Simulation.
AB  - Presented herein is a novel headspace single drop microextraction (HS-SDME) based
      on temperature gradient (TG) for an on-site preconcentration technique of
      volatile and semivolatile samples. First, an inner vial cap was designed as a
      cooling device for acceptor droplet in HS-SDME unit to achieve fast and efficient
      microextraction. Second, for the first time, an in-vial TG was generated between
      the donor phase in a sample vial at 80  degrees C and the acceptor droplet under
      the inner vial cap containing cooling liquid at -20  degrees C for a TG-HS-SDME.
      Third, a simple mathematic model and numerical simulations were developed by
      using heat transfer in fluids, Navier-Stokes and mass balance equations for
      conditional optimization, and dynamic illumination of the proposed extraction
      based on COMSOL Multiphysics. Five chlorophenols (CPs) were selected as model
      analytes to authenticate the proposed method. The comparisons revealed that the
      simulative results were in good agreement with the quantitative experiments,
      verifying the design of TG-HS-SDME via the numerical simulation. Under the
      optimum conditions, the extraction enrichments were improved from 302- to 388
      fold within 2 min only, providing 3.5 to 4 times higher enrichment factors as
      compared to a typical HS-SDME. The simulation indicated that these improvements
      in the extraction kinetics could be attributed due to the applied temperature gap
      between the sample matrix and acceptor droplet within the small volume of
      headspace. Additionally, the experiments demonstrated a good linearity (0.03-100
      MUg/L, R2 > 0.9986), low limit of detection (7-10 ng/L), and fair repeatability
      (<5.9% RSD, n = 6). All of the simulative and experimental results indicated the
      robustness, precision, and usefulness of TG-HS-SDME for trace analyses of
      analytes in a wide variety of environmental, pharmaceutical, food safety, and
      forensic samples.

PMID- 27715051
TI  - Comment on "Osmolyte Effects on Monoclonal Antibody Stability and Concentration
      Dependent Protein Interactions with Water and Common Osmolytes".

PMID- 27715050
TI  - Solution Conformations of Curcumin in DMSO.
AB  - NAMFIS (NMR Analysis of Molecular Flexibility In Solution) has been applied to
      curcumin dissolved in DMSO. Quantitative 1H-1H distance constraints reduce a pool
      of candidate conformations to a solution collection of four enol conformations
      two of these match curcumin crystallized with human transthyretin, and one is
      closely related to a single-crystal structure of curcumin.

PMID- 27715052
TI  - Absolute pKas of Sulfonamides in Ionic Liquids: Comparisons to Molecular
      Solvents.
AB  - Absolute pKas of 25 sulfonamides in four ionic liquids (ILs) were measured
      spectroscopically with high precision and subsequently compared with those in
      conventional molecular solvents. It is found that the acidity order of these
      sulfonamides is as follows: in water > in DMSO > in ILs > in acetonitrile (ACN).
      The well-known solvent polarity index epsilon fails to explain the observed
      stronger bond-weakening effect of ILs in comparison to that of ACN, whose epsilon
      value is much greater. In addition, the regression analyses show that the pKas of
      sulfonamides determined in ILs linearly correlate with these in molecular
      solvents of distinct properties, but with various slopes. A rationale and related
      discussion on the effect of solvation in ILs are presented.

PMID- 27715053
TI  - Pesticide Chemical Research in Toxicology: Lessons from Nature.
AB  - Pesticide researchers are students of nature, and each new compound and mechanism
      turns a page in the ever-expanding encyclopedia of life. Pesticides are both
      probes to learn about life processes and tools for pest management to facilitate
      food production and enhance health. In contrast to some household and industrial
      chemicals, pesticides are assumed to be hazardous to health and the environment
      until proven otherwise. About a thousand current pesticides working by more than
      100 different mechanisms have helped understand many processes and coupled
      events. Pesticide chemical research is a major source of toxicology information
      on new natural products, novel targets or modes of action, resistance mechanisms,
      xenobiotic metabolism, selective toxicity, safety evaluations, and
      recommendations for safe and effective pest management. Target binding site
      models help define the effect of substituent changes and predict modifications
      for enhanced potency and safety and circumvention of resistance. The contribution
      of pesticide chemical research in toxicology is illustrated here with two each of
      the newer or most important insecticides, herbicides, and fungicides. The
      insecticides are imidacloprid and chlorantraniliprole acting on the nicotinic
      acetylcholine receptor and the ryanodine receptor Ca2+ channel, respectively. The
      herbicides are glyphosate that inhibits aromatic amino acid biosynthesis and
      mesotrione that prevents plastoquinone and carotenoid formation. The fungicides
      are azoxystrobin inhibiting the Qo site of the cytochrome bc1 complex and
      prothioconazole inhibiting the 14alpha-demethylase in ergosterol biosynthesis.
      The two target sites involved for each type of pesticide account for 27-40% of
      worldwide sales for all insecticides, herbicides, and fungicides. In each case,
      selection for resistance involving a single amino acid change in the binding site
      or detoxifying enzyme circumvents the pesticide chemists's structure optimization
      and guarantees survival of the pest and a continuing job for the design chemist.
      These lessons from nature are a continuing part of pest management and
      maintaining human and environmental health.

PMID- 27715054
TI  - Radiative Monomolecular Recombination Boosts Amplified Spontaneous Emission in
      HC(NH2)2SnI3 Perovskite Films.
AB  - Hybrid metal-halide perovskites have potential as cost-effective gain media for
      laser technology because of their superior optoelectronic properties. Although
      lead-halide perovskites have been most widely studied to date, tin-based
      perovskites have been proposed as a less toxic alternative. In this Letter, we
      show that amplified spontaneous emission (ASE) in formamidinium tin triiodide
      (FASnI3) thin films is supported by an observed radiative monomolecular charge
      recombination pathway deriving from its unintentional doping. Such a radiative
      component will be active even at the lowest charge-carrier densities, opening a
      pathway for ultralow light-emission thresholds. Using time-resolved THz
      photoconductivity analysis, we further show that the material has an
      unprecedentedly high charge-carrier mobility of 22 cm2 V-1 s-1 favoring efficient
      transport. In addition, FASnI3 exhibits strong radiative bimolecular
      recombination and Auger rates that are over an order of magnitude lower than for
      lead-halide perovskites. In combination, these properties reveal that tin-halide
      perovskites are highly suited to light-emitting devices.

PMID- 27715055
TI  - General Mechanism of Osmolytes' Influence on Protein Stability Irrespective of
      the Type of Osmolyte Cosolvent.
AB  - The stability of proteins in an aqueous solution can be modified by the presence
      of osmolytes. The hydration sphere of stabilizing osmolytes is strikingly similar
      to the enhanced hydration sphere of a protein. This similarity leads to an
      increase in the protein stability. Moreover, the hydration sphere of
      destabilizing osmolytes is significantly different. These solutes generate in
      their surroundings so-called "structurally different water". The addition of such
      osmolytes causes "dissolution" of the specific protein hydration sphere and
      destabilizes its folded form. No relationship is seen between the
      stabilizing/destabilizing properties of osmolytes and their structure-making/
      breaking influence on water. Furthermore, their accumulation at the protein
      surface or their exclusion does not determine the osmolytes' effect on protein
      stability. An explanation to the osmolytes' stabilizing/destabilizing influence
      originates in the similarity of water properties in osmolytes and protein
      solutions. The spectral infrared characteristic of water in an osmolyte solution
      allowed us to develop practical criteria for classifying solutes as stabilizing
      or destabilizing agents.

PMID- 27715056
TI  - Photogeneration and Mobility of Charge Carriers in Atomically Thin Colloidal InSe
      Nanosheets Probed by Ultrafast Terahertz Spectroscopy.
AB  - The implementation of next generation ultrathin electronics by applying highly
      promising dimensionality-dependent physical properties of two-dimensional (2D)
      semiconductors is ever increasing. In this context, the van der Waals layered
      semiconductor InSe has proven its potential as photodetecting material with high
      charge carrier mobility. We have determined the photogeneration charge carrier
      quantum yield and mobility in atomically thin colloidal InSe nanosheets
      (inorganic layer thickness 0.8 - 1.7 nm, mono-/double-layers, <=5 nm including
      ligands) by ultrafast transient terahertz (THz) spectroscopy. A near unity
      quantum yield of free charge carriers is determined for low photoexcitation
      density. The charge carrier quantum yield decreases at higher excitation density,
      due to recombination of electrons and holes, leading to the formation of neutral
      excitons. In the THz frequency domain we probe a charge mobility as high as 20 +/
      2 cm2/Vs. The THz mobility is similar to field-effect transistor mobilities
      extracted from unmodified exfoliated thin InSe devices. The current work provides
      the first results on charge carrier dynamics in ultrathin colloidal InSe
      nanosheets.

PMID- 27715058
TI  - Effect of Nitrogen Management on Structure and Physicochemical Properties of Rice
      Starch.
AB  - Nitrogen management (nitrogen application ratio in transplanting, tillering, and
      panicle initiation growth stages) is an important parameter in crop cultivation
      and is closely associated with rice yield and grain quality. The physicochemical
      and structural properties of starches separated from two rice varieties grown
      under four different nitrogen management ratios (0; 9:1; 7:3; 6:4) were
      investigated. As the percentage of fertilizer used in the panicle initiation
      stage increased, the content of small granules increased while the content of
      large granules decreased, the decreased amylose content resulting high selling
      power, water solubility, gelatinization enthalpy and low retrogradation. The
      crystallinity of the starch samples was found to be A-type. This study indicated
      that the best nitrogen management ratio for the cultivation of rice with the
      highest yield, desirable starch physicochemical properties for high quality
      cooked rice, and a moderate protein level was 7:3.

PMID- 27715057
TI  - Structure Determinants of Lagunamide A for Anticancer Activity and Its Molecular
      Mechanism of Mitochondrial Apoptosis.
AB  - Marine natural products are served as attractive source of anticancer
      therapeutics, with the great success of "first-in-class" drugs, such as Yondelis,
      Halaven, and Brentuximab vendotin. Lagunamides A-C from marine cyanobacterium,
      Lyngbya majuscula, exhibit exquisite growth inhibitory activities against cancer
      cells. In this study, we have systematically investigated the structure-activity
      relationships (SARs) of a concise collection of lagunamide A and its analogues
      constructed by total chemical synthesis against a broad panel of cancer cells
      derived from various tissues or organs, including A549, HeLa, U2OS, HepG2, BEL
      7404, BGC-823, HCT116, MCF-7, HL-60, and A375. The R configuration of lagunamide
      A at C-39 position was found to be the structure determinant for anticancer
      activity. Further molecular mechanism study in A549 cells revealed that
      lagunamide A induced caspase-mediated mitochondrial apoptosis. Accompanied with
      the dissipation of mitochondrial membrane potential (Deltaphim) and
      overproduction of reactive oxygen species (ROS), lagunamide A led to
      mitochondrial dysfunction and finally caused cell death. Moreover, both anti- and
      pro-apoptotic B-cell lymphoma 2 (Bcl-2) family proteins participated in
      lagunamide A-induced mitochondrial apoptosis, especially myeloid cell leukemia-1
      (Mcl-1). Overexpression of Mcl-1 partly rescued A549 cells from lagunamide A
      induced apoptosis. This study suggests that lagunamide A may exert anticancer
      property through mitochondrial apoptosis. Together, our findings would provide
      insightful information for the design of new anticancer drugs derived from
      lagunamides.

PMID- 27715059
TI  - Supramolecularly Assisted Modulation of Optical Properties of BODIPY
      Benzimidazole Conjugates.
AB  - Supramolecular host-guest interaction of neutral and cationic (protonated) forms
      of two boron-dipyromethane (BODIPY)-benzimidazole (mono- and di-benzimidazole)
      conjugate dyes with the macrocyclic host cucurbit[7]uril (CB7) has been
      investigated using photophysical and density functional theory studies.
      Expectedly, cationic forms of the dyes show exceptionally stronger binding than
      that of the neutral forms with CB7, which can be ascribed to the strong ion
      dipole interaction between the positive charge of the dye and the highly
      polarizable carbonyl portals of the host. The formation of dye-host inclusion
      complexes is supported by the significant changes in the photophysical properties
      and longer rotational relaxation times of the dye in the presence of CB7. Job's
      plot studies indicate the formation of a 1:1 inclusion complex for the mono and a
      1:2 inclusion complex for the dibenzimidazole BODIPY dyes. Quantum chemical
      calculations are in good agreement with the inferences outlined from
      photophysical measurements. Findings from the studied dye-CB7 systems are of
      direct relevance to applications such as drug delivery, aqueous dye lasers,
      sensors, and so on.

PMID- 27715060
TI  - Controlled Generation of a p-n Junction in a Waveguide Integrated Graphene
      Photodetector.
AB  - With its electrically tunable light absorption and ultrafast photoresponse,
      graphene is a promising candidate for high-speed chip-integrated photonics. The
      generation mechanisms of photosignals in graphene photodetectors have been
      studied extensively in the past years. However, the knowledge about efficient
      light conversion at graphene p-n junctions has not yet been translated into high
      performance devices. Here, we present a graphene photodetector integrated on a
      silicon slot-waveguide, acting as a dual gate to create a p-n junction in the
      optical absorption region of the device. While at zero bias the
      photothermoelectric effect is the dominant conversion process, an additional
      photoconductive contribution is identified in a biased configuration. Extrinsic
      responsivities of 35 mA/W, or 3.5 V/W, at zero bias and 76 mA/W at 300 mV bias
      voltage are achieved. The device exhibits a 3 dB bandwidth of 65 GHz, which is
      the highest value reported for a graphene-based photodetector.

PMID- 27715061
TI  - The Template Determines Whether Chemically Identical Nanoparticle Scaffolds Show
      Elastic Recovery or Plastic Failure.
AB  - Subtle variations in the preparation of ice-templated nanoparticle assemblies
      yield monoliths that are chemically identical but exhibit qualitatively different
      mechanical behavior. We ice template aqueous dispersions to prepare macroporous
      monoliths largely comprising silica nanoparticles held together by a crosslinked
      polymer mesh. When the polymer is crosslinked in the presence of ice crystals, we
      obtain an elastic sponge that is capable of recovery after imposition of large
      compressive strains (up to 80%). If, however, the ice is lyophilized before the
      polymer is crosslinked, we obtain a plastic monolith that fails even for modest
      strains (less than 10%). The elastic sponge and the plastic monolith are
      chemically identical; they have the same organic content, the same ratio of
      polymer to crosslinker, and the same average crosslink density. Atomic force
      microscopy (AFM) was used to probe the local mechanical properties of the
      crosslinked polymer mesh. These measurements indicate that plastic monoliths
      dissipate significantly more energy and have a larger spatial variation in local
      mechanical response relative to the elastic sponges. We believe that this
      behavior might correlate with a wider spatial distribution of crosslinks in
      plastic scaffolds relative to elastic scaffolds.

PMID- 27715062
TI  - Synthesis of Triphenylenes Starting from 2-Iodobiphenyls and Iodobenzenes via
      Palladium-Catalyzed Dual C-H Activation and Double C-C Bond Formation.
AB  - A novel and facile approach for the synthesis of triphenylenes has been developed
      via palladium-catalyzed coupling of 2-iodobiphenyls and iodobenzenes. The
      reaction involves dual palladium-catalyzed C-H activations and double palladium
      catalyzed C-C bond formations. A range of unsymmetrically functionalized
      triphenylenes can be synthesized with the reaction. The approach features readily
      available starting materials, high atom- and step-economy, and access to various
      unsymmetrically functionalized triphenylenes.

PMID- 27715063
TI  - "Staying Out" Rather than "Cracking In": Asymmetric Membrane Insertion of 12:0
      Lysophosphocholine.
AB  - Interactions between detergents and model membranes are well described by the
      three-stage model: saturation and solubilization boundaries divide bilayer-only,
      bilayer-micelle coexistence, and micelle-only ranges. An underlying assumption of
      the model is the equilibration of detergent between the two membrane leaflets.
      However, many detergents partition asymmetrically at room temperature due to slow
      flip-flop, such as sodium dodecyl sulfate (SDS) and lysolipids. In this work, we
      use isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) to
      investigate the solubilization of unilamellar POPC vesicles by 12:0
      lysophosphocholine (12:0 LPC). Flip-flop of 12:0 LPC occurs beyond the time scale
      of our experiments, which establish a characteristic nonequilibrated state with
      asymmetric distribution: 12:0 LPC partitions primarily into the outer leaflet.
      Increasing asymmetry stress in the membrane does not lead to membrane failure,
      i.e., "cracking in" as seen for alkyl maltosides and other surfactants; instead,
      it reduces further membrane insertion which leads to the "staying out" of 12:0
      LPC in solution. At above the critical micellar concentration of 12:0 LPC in the
      presence of the membrane, micelles persist and accommodate further LPC but take
      up lipid from vesicles only very slowly. Ultimately, solubilization proceeds via
      the micellar mechanism (Kragh-Hansen et al., 1995). With a combination of
      demicellization and solubilization experiments, we quantify the molar ratio
      partition coefficient (0.6 +/- 0.1 mM-1) and enthalpy of partitioning (6.1 +/-
      0.3 kJ.mol-1) and estimate the maximum detergent/lipid ratio reached in the outer
      leaflet (<0.13). Despite the inapplicability of the three-stage model to 12:0 LPC
      at room temperature, we are able to extract quantitative information from ITC
      solubilization experiments and DLS that are important for the understanding of
      asymmetry-dependent processes such as endocytosis and the gating of
      mechanosensitive channels in vitro.

PMID- 27715064
TI  - A Pseudopolyrotaxane for Glucose-Responsive Insulin Release: The Effect of
      Binding Ability and Spatial Arrangement of Phenylboronic Acid Group.
AB  - A pseudopolyrotaxane (PPRX) comprising 3-carboxy-5-nitrophenylboronic acid
      modified gamma-cyclodextrin (NPBA-gamma-CyD) and naphthalene modified
      polyethylene glycol (Naph-PEG) as a sugar-responsive supramolecular structure is
      prepared. The binding of sugar by the NPBA group induced disintegration of the
      Naph-PEG/NPBA-gamma-CyD PPRX, allowing the components to be dissolved. The Naph
      PEG/NPBA-gamma-CyD PPRX exhibited better sensitivity compared to that of a PPRX
      based on 4-carboxyphenylboronic acid modified gamma-cyclodextrin (PBA-gamma-CyD).
      We have previously reported the unique structure of Naph-PEG/PBA-gamma-CyD PPRX,
      which formed an inclusion complex with a single-stranded PEG chain being threaded
      through the gamma-CyD rings, with the remaining internal space being occupied by
      the sugar-sensing PBA moiety from a neighboring ring, thus shielding it from
      sugar molecules and reducing the sugar sensitivity of the PPRX. In contrast,
      structural analyses in this study revealed that the sugar-sensing NPBA moiety in
      the Naph-PEG/NPBA-gamma-CyD PPRX is not included in the neighboring NPBA-gamma
      CyD. This spatial arrangement and the high affinity of NPBA for sugar contributed
      to the improved sugar responsivity. The enhanced NPBA-gamma-CyD was then applied
      to a PPRX containing Naph-PEG-appended insulin (Naph-PEG-Ins) that showed an
      improved response for glucose-induced insulin release.

PMID- 27715065
TI  - ToF-SIMS and Principal Component Analysis Investigation of Denatured, Surface
      Adsorbed Antibodies.
AB  - Antibody denaturation at surface-liquid interfaces plays an important role in the
      sensitivity of protein assays such as enzyme-linked immunosorbent assays
      (ELISAs). Surface immobilized antibodies must maintain their native state, with
      their antigen binding (Fab) region intact, to capture antigens from biological
      samples and permit disease detection. In this work, two identical sample sets
      were prepared with whole antibody IgG, F(ab')2 and Fc fragments, immobilized to
      either a silicon wafer, or a diethylene glycol dimethyl ether plasma polymer
      surface. Analysis was conducted on one sample set at Day 0, and the second sample
      set after 14 days in vacuum, with time-of-flight secondary-ion mass spectrometry
      (ToF-SIMS) for molecular species representative of denaturation. A 1003 mass
      fragment peak list was compiled from ToF-SIMS data and compared to a 35 amino
      acid mass fragment peak list using principal component analysis. Several ToF-SIMS
      secondary-ions, pertaining to disulfide and thiol species, were identified in the
      14 day (presumably denatured) samples. A substrate and primary-ion independent
      marker for denaturation (ageing) was then produced using a ratio of mass peak
      intensities according to; Denaturation Ratio?
      [I_61.95+I_62.98+I_122.95+I_78.96+I_84.96+I_120.95
      ]/[I_30.99+I_42.99+I_73.06+I_147.07+I_207.03 ] The ratio successfully identifies
      denaturation on both the silicon and plasma polymer substrates and for spectra
      generated with Mn+, Bi+, and Bi3+ primary ions. We believe this ratio could be
      employed to as a marker of denaturation of antibodies on a plethora of
      substrates.

PMID- 27715066
TI  - Tracing Dynamics, Self-Diffusion, and Nanoscale Structural Heterogeneity of Pure
      and Binary Mixtures of Ionic Liquid 1-Hexyl-2,3-dimethylimidazolium
      Bis(fluorosulfonyl)imide with Acetonitrile: Insights from Molecular Dynamics
      Simulations.
AB  - All-atom molecular dynamics (MD) simulations of the ionic liquid (IL) 1-hexyl-2,3
      dimethylimidazolium bis(fluorosulfonyl)imide ([C6mmim][FSI]) and its binary
      mixtures with acetonitrile (ACN) have been reported for the first time. The
      presence of ACN as a cosolvent, similar to the effect of increasing temperature,
      causes enhancements in the ion translational motion and fluidity of the IL,
      leading to significant improvement of ionic conductivity and self-diffusion,
      which is well explained by a microscopic structural analysis. In neat IL and a
      concentrated IL mixture, self-diffusion of the cation is higher than that of the
      corresponding anion; however, further addition of ACN into the diluted mixtures
      with IL molar fractions (xIL's) below 0.50 results in more weakened interactions
      among the nearest ACN-anion neighbors compared to those among the ACN-cation
      neighbors so that the number of isolated anions is more than that of isolated
      cations under this condition, and the anions diffuse faster than the cations, as
      expected on the basis of their relative sizes. The velocity autocorrelation
      function analysis indicates an inverse relation between xIL and the mean
      collision time of each species. Additionally, at a fixed xIL, both the mean
      collision time and velocity randomization time of ACN are shorter than those of
      the ions. Gradual addition of ACN changes the morphology of nanosegregated
      domains and tends to disrupt ionic clusters (i.e., it scatters and decomposes
      both the polar and nonpolar domains) compared with pure IL, whereas both the
      radial and spatial distribution functions show the stabilization role of ACN in
      the close-contact ion-pair association. On the other hand, increasing ACN causes
      weakening of the structural correlations of the cation-cation and anion-anion
      neighbors in the solutions. ACN molecules appeared as a bridge, with balanced
      affinities between the polar and nonpolar domains, and no indication was observed
      for aggregation of ACN molecules in the studied mixtures that can rationalize
      good miscibility with imidazolium-based ILs.

PMID- 27715067
TI  - Molecular Scale Description of Anion Competition on Amine-Functionalized
      Surfaces.
AB  - Many industrial and biological processes involve the competitive adsorption of
      ions with different valencies and sizes at charged surfaces; heavy and precious
      metal ions are separated on the basis of their propensity to adsorb onto
      interfaces, often as anionic ion clusters (e.g., [MClx]n-). However, very little
      is known, both theoretically and experimentally, about the competition of factors
      that drive preferential adsorption, such as charge density or valence, at
      interfaces in technologically relevant systems. There are even contradictory
      pictures described by interfacial studies and real life applications, such as
      chlorometalate extractions, in which charge diffuse chlorometalate ions are
      extracted efficiently even though charge dense chloride ions present in the
      background are expected to occupy the interface. We studied the competition
      between divalent chlorometalate anions (PtCl62- and PdCl42-) and monovalent
      chloride anions on positively charged amine-functionalized surfaces using in situ
      specular X-ray reflectivity. Chloride anions were present in vast excess to
      simulate the conditions used in the commercial separation of heavy and precious
      metal ions. Our results suggest that divalent chlorometalate adsorption is a two
      step process and that the divalent anions preferentially adsorb at the interface
      despite having a charge/volume ratio lower than that of chloride. These results
      provide fundamental insight into the structural mechanisms that underpin
      transport in phases that are relevant to heavy and precious metal ion
      separations, explaining the high efficiency of low charge density ion transport
      processes in the presence of charge dense anions.

PMID- 27715068
TI  - Rh(I)-Catalyzed 1,4-Conjugate Addition of Alkenylboronic Acids to a
      Cyclopentenone Useful for the Synthesis of Prostaglandins.
AB  - An efficient and trans-diastereoselective Rh(I)-catalyzed 1,4-conjugate addition
      reaction of alkenylboronic acids and a homochiral (R)-4-silyloxycyclopentenone
      useful for the synthesis of derivatives of prostaglandins E and F is described
      for the first time. The reaction functions under mild conditions and is
      particularly rapid (<=6 h) under low power (50 W) microwave irradiation at 30 
      degrees C in MeOH in the presence of a catalytic amount of KOH. Under these
      conditions, 3 mol % of [RhCl(COD)]2 is typically required to produce high yields.
      The method also functions without microwave irradiation at 3  degrees C in the
      presence of a stoichiometric amount of KOH. Under these conditions, only 1.5 mol
      % of [RhCl(COD)]2 is needed, but the reaction is considerably slower. The method
      accepts a range of aryl- and alkyl-substituted alkenylboronic acids, and its
      utility has been demonstrated by the synthesis of PGF2alpha (dinoprost) and
      tafluprost.

PMID- 27715069
TI  - Modular Synthetic Route to Monofunctionalized Porphyrin Architectures.
AB  - The synthesis of a borylated Ni2+ porphyrin and its application as a versatile
      precursor for building up functional ortho-substituted tetraaryl porphyrin
      architectures is reported. This precursor porphyrin provides the basis for
      efficient modular syntheses of porphyrin compounds with covalently attached axial
      ligands which are important as enzyme model complexes, electron transfer dyads,
      and many other applications. In the present study, the precursor porphyrin was
      used for the synthesis of molecular spin switches which previously showed high
      potential as photoresponsive contrast agents for magnetic resonance imaging.

PMID- 27715070
TI  - [Clinically relevant possibilities and limits of differential diagnosis of
      megaloblastic anemia and myelodysplastic syndrome - refractory anemia type in
      bone marrow biopsies].
AB  - INTRODUCTION: Megaloblastic anemia (MA) represents a subtype of macrocytic anemia
      caused by impaired DNA synthesis, mostly due to folate and vitamin B12
      deficiency. Its mildest forms lead to macrocytosis without concomitant anemia,
      but more severe forms to thrombocytopenia and/or leucopenia as well. In majority
      of the cases, the diagnosis of MA dose not represent a serious clinical problem,
      however, other causes of macrocytosis including myelodysplastic syndrome (MDS)
      must be excluded. MATERIAL AND METHODS: In the period 2004-2015 we identified in
      our registry 126 consecutive bone marrow (BM) biopsies of patients with
      cytopenia/s in peripheral blood and suspicion either on MA or MDS of refractory
      anemia (RA) type. We performed a retrospective analysis of BM biopsies focused on
      evaluation of parameters useful for the differential diagnosis, as represented by
      (a) cellularity and proportions of BM precursors, (b) and their topography, (c)
      presence of maturation defects and dysplastic changes, (d) grade and extent of
      myelofibrosis, (e) iron deposits and (f) presence of "inflammatory" response in
      BM. Histological analyses were supported by immunohistochemical examinations.
      RESULTS: The series consisted of biopsies of 126 patients (61 men and 65 women)
      with average age 63 (14-88 years) - almost all patients (121/126) presented with
      anemia. Based on the findings we distinguished three diagnostic groups - MA (31
      patients), MDS-RA (39) and bioptically unclasifiable case ("DIF DG" - 56
      patients). Abnormalities of the BM cellularity were observed in 81 % and of
      topography in 73 % of all cases respectively. Megalobastic differentiation of
      erythropoesis was detected in 79 % and diagnostic dysplastic changes in 25 % of
      all biopsy cases. In 29 % of all biopsies ring sideroblasts were present,
      megakaryocytic nuclear lobulisation defects density changes were found in 61 % of
      all patients. In 14 % of all biopsies the BM myelofibrosis was absent, in
      contrast 5 % of the biopsies showed severe diffuse fibrosis. "Inflammatory"
      response was developed in 44 % of all biopsies. Iron deposits were absent in 26
      %, decreased in 35 % and increased in 33 % of all the cases. CONCLUSIONS: From
      the point of view of histopathologist it seems to be difficult to distinguish BM
      hematopoietic changes in patients with MA and MDS-RA respectivelly, as
      histological examinations allowed determination of a definitive and correct
      diagnosis in about 55% of the cases. The crucial problem represents a decision
      whether the observed changes really result from the development of a clonal
      disease.Key words: megaloblastic anemia - megaloblastic differentiation -
      refractory anemia.

PMID- 27715071
TI  - [Current position of a fixed combination telmisartan with amlodipine in treatment
      of essential arterial hypertension].
AB  - Nowadays, fixed drug combinations are very important part of pharmacotherapy in
      essential arterial hypertension. The ameliorated activity of RAAS system (ACE
      inhibitors or sartans) along with calcium-ion channel inhibitor results in
      additive decrease of blood pressure with concomitant beneficial safety profile.
      Both telmisartan and amlodipine possess very favorable pharmacological
      properties, what is reflected in results of performed clinical trials, in which
      they were used as combinations.Key words: amlodipine - calcium channel blockers -
      fixed combination - hypertension - sartans - telmisartan.

PMID- 27715072
TI  - [Clinical efficacy and safety of basal insulin analogue glargine in patients with
      type 2 diabetes mellitus].
AB  - Basal insulin has a clearly defined position in the recommendations for the
      treatment of patients with type 2 diabetes mellitus. General most common
      indication for administration is the addition in situation of the failure of
      noninsulin antidiabetic therapy or early insulin treatment of diabetes, as one of
      the second choice after metformin. In the recent years there is significant
      expansion of the range of antidiabetic drugs, including basal insulin analogues.
      In connection with the introduction of concentrated long-acting basal insulin
      analogues into the clinical practice many questions regarding clinical efficacy
      and safety raises especially comparing with the "classical" basal insulin
      analogues. Although it is very likely that in the current clinical practice these
      differences in a number of indications are of minimal impact, it is possible that
      in some situations clinically relevant differences can be found among the basal
      insulin analogues.Key words: basal insulin analogues - concentrated insulin -
      diabetes mellitus - EDITION trial - glargine - hypoglycemia - insulin therapy.

PMID- 27715073
TI  - [Schnitzlers SyndromeDifferential diagnostics, an overview of therapeutic options
      and description of 5 cases treated with anakinra].
AB  - Schnitzlers syndrome is an acquired auto-inflammatory disease of still unclear
      origin. The Strasbourg criteria were adopted (non-infectious fever, chronic
      urticaria, changes in the bone structure, leukocytosis and higher values of
      inflammatory markers - CRP and presence of monoclonal immunoglobulin mostly of
      type IgM, very rarely of IgG) to establish this diagnosis. The first-choice
      therapy for this disease is the blocking of interleukin-1 effects. In practice,
      the interleukin-1 receptor antagonist, anakinra, is the most commonly used.
      Currently reports also appear of the use of other medicines blocking the effect
      of interleukin-1, namely canakinumab and rilonacept. We have been treating 5
      patients with anakinra (108, 72, 33, 32 and 1 months) on a long-term basis. In
      all the patients, we commenced administration of anakinra in a dose of 100 mg
      once a day. As a result of 100 mg being administered once a day, all symptoms
      went away completely in 4 patients, while they receded by about 75 % in 1
      patient, without disappearing completely. This patient needs an increased dose of
      2 ampoules per day on the days of spontaneously intensified medical ailments.
      After one year of treatment it turned out for one of the four patients whose
      symptoms had completely disappeared when administered the 100mg daily dose, that
      he only needed the respective dose of anakinra at 48-hour intervals. However this
      patient does not tolerate further extension of the intervals between dose
      administrations. We have not recorded any adverse effects of anakinra in the
      course of the treatment, and no decline in the efficiency of anakinra has been
      observed: it acts as effectively now as it did at the beginning of the treatment.
      The text discusses the differential diagnostics of the Schnitzler syndrome.Key
      words: anakinra - auto-inflammatory diseases - canakinumab - fever of unknown
      origin - FUO - interleukin 1 - cryopyrin-associated autoinflammatory syndrome
      (CAPS) - monoclonal gammopathy - rilonacept - Schnitzlers Syndrome - Adult Stills
      disease.

PMID- 27715074
TI  - [Arrhythmogenic left ventricular cardiomyopathy].
AB  - Arrhythmogenic left ventricular cardiomyopathy (ALVC) is a rare condition
      characterised by progressive fibrofatty replacement of the myocardium of the left
      ventricle in combination with arrhythmias of left ventricular origin. ALVC has
      been linked to autosomal dominant mutations of genes encoding desmosomal
      proteins, similarly to the classic arrhythmogenic right ventricular
      cardiomyopathy with which it also shares pathological and prognostic features. It
      seems that isolated left or right ventricular abnormalities represent two
      extremes of the spectrum of clinical manifestations of a single disease:
      arrhythmogenic cardiomyopathy. In addition to arrhythmias originating from the
      left ventricle, the diagnosis of ALVC is based on identification of morphological
      changes of the left ventricle including late gadolinium enhancement with
      subepicardial to midwall distribution, corresponding to fibrous or fibrofatty
      replacement on histopathology. The diagnosis is confirmed by detection of a
      causal mutation. ALVC should be kept in mind in the differential diagnosis of
      ventricular tachycardia of non-ischemic origin.Key words: arrhythmogenic
      cardiomyopathy - cardiac magnetic resonance - late gadolinium enhancement -
      ventricular tachycardia.

PMID- 27715075
TI  - [Current treatment options for hereditary angioedema].
AB  - Hereditarni angioedem je vzacne dominantne dedicne onemocneni zpusobene deficitem
      inhibitoru C1-esterazy (C1-INH). Onemocneni se klinicky projevuje recidivami
      lokalizovanych otoku podkozi a sliznic. Nemoc je hendikepujici a muze byt i
      smrtelna. Charakteristicka je extremni variabilita v cetnosti a zavaznosti
      symptomu. Clanek se zabyva organizaci pece o pacienty a zahrnuje aktualni lecebne
      moznosti onemocneni. Strategie lecby zahrnuje kratkodobou a dlouhodobou profylaxi
      a lecbu atak. V soucasne dobe lecebne moznosti zahrnuji atenuovane androgeny,
      antifibrinolytika, rekombinantni (rhC1-INH) a plazma derivovane (pdC1-INH) C1
      INH, antagonistu bradykininoveho receptoru a inhibitor kalikreinu. V Ceske
      republice je pece od roku 2011 soustredena do 4 diagnosticko-terapeutickych
      center.Klicova slova: bradykininovy receptor - C1 inhibitor - hereditarni
      angioedem - komplementovy system.

PMID- 27715076
TI  - [Oral anticoagulants for primary and secondary prevention of venous
      thromboembolism].
AB  - Until recently, vitamin K antagonists (VKA; predominantly warfarin) were the only
      oral anticoagulants for primary and secondary prevention of venous
      thromboembolism. Prevention and therapy with novel, direct, non-VKA oral
      anticoagulant agents (NOACs; DOACs: dabigatran, rivaroxaban, apixaban, edoxaban),
      have recently become available as an alternative to VKA. NOACs have been shown to
      be non-inferior or superior to VKA in clinical trials. Available results suggest
      that real world safety of NOACs is mostly consistent with results observed in
      clinical trials. The most effective method is triple simultaneous prevention of
      venous thromboembolism (pharmaco kinezio mechano
      phlebothromboemboloprophylaxis).Key words: oral anticoagulants - NOAC/DOAC -
      thromboprophylaxis - venous thromboembolism - VKA.

PMID- 27715077
TI  - Nuclear Binding Near a Quantum Phase Transition.
AB  - How do protons and neutrons bind to form nuclei? This is the central question of
      ab initio nuclear structure theory. While the answer may seem as simple as the
      fact that nuclear forces are attractive, the full story is more complex and
      interesting. In this work we present numerical evidence from ab initio lattice
      simulations showing that nature is near a quantum phase transition, a zero
      temperature transition driven by quantum fluctuations. Using lattice effective
      field theory, we perform Monte Carlo simulations for systems with up to twenty
      nucleons. For even and equal numbers of protons and neutrons, we discover a first
      order transition at zero temperature from a Bose-condensed gas of alpha particles
      (^{4}He nuclei) to a nuclear liquid. Whether one has an alpha-particle gas or
      nuclear liquid is determined by the strength of the alpha-alpha interactions, and
      we show that the alpha-alpha interactions depend on the strength and locality of
      the nucleon-nucleon interactions. This insight should be useful in improving
      calculations of nuclear structure and important astrophysical reactions involving
      alpha capture on nuclei. Our findings also provide a tool to probe the structure
      of alpha cluster states such as the Hoyle state responsible for the production of
      carbon in red giant stars and point to a connection between nuclear states and
      the universal physics of bosons at large scattering length.

PMID- 27715078
TI  - Noise-Resilient Quantum Computing with a Nitrogen-Vacancy Center and Nuclear
      Spins.
AB  - Selective control of qubits in a quantum register for the purposes of quantum
      information processing represents a critical challenge for dense spin ensembles
      in solid-state systems. Here we present a protocol that achieves a complete set
      of selective electron-nuclear gates and single nuclear rotations in such an
      ensemble in diamond facilitated by a nearby nitrogen-vacancy (NV) center. The
      protocol suppresses internuclear interactions as well as unwanted coupling
      between the NV center and other spins of the ensemble to achieve quantum gate
      fidelities well exceeding 99%. Notably, our method can be applied to weakly
      coupled, distant spins representing a scalable procedure that exploits the
      exceptional properties of nuclear spins in diamond as robust quantum memories.

PMID- 27715079
TI  - Interfacial Free Energy as the Key to the Pressure-Induced Deceleration of Ice
      Nucleation.
AB  - The avoidance of water freezing is the holy grail in the cryopreservation of
      biological samples, food, and organs. Fast cooling rates are used to beat ice
      nucleation and avoid cell damage. This strategy can be enhanced by applying high
      pressures to decrease the nucleation rate, but the physics behind this procedure
      has not been fully understood yet. We perform computer experiments to investigate
      ice nucleation at high pressures consisting in embedding ice seeds in supercooled
      water. We find that the slowing down of the nucleation rate is mainly due to an
      increase of the ice I-water interfacial free energy with pressure. Our work also
      clarifies the molecular mechanism of ice nucleation for a wide pressure range.
      This study is not only relevant to cryopreservation, but also to water
      amorphization and climate change modeling.

PMID- 27715080
TI  - Theory of Acoustic Raman Modes in Proteins.
AB  - We present a theoretical analysis that associates the resonances of extraordinary
      acoustic Raman (EAR) spectroscopy [Wheaton et al., Nat. Photonics 9, 68 (2015)]
      with the collective modes of proteins. The theory uses the anisotropic elastic
      network model to find the protein acoustic modes, and calculates Raman intensity
      by treating the protein as a polarizable ellipsoid. Reasonable agreement is found
      between EAR spectra and our theory. Protein acoustic modes have been extensively
      studied theoretically to assess the role they play in protein function; this
      result suggests EAR spectroscopy as a new experimental tool for studies of
      protein acoustic modes.

PMID- 27715081
TI  - Self-Induced Glassiness and Pattern Formation in Spin Systems Subject to Long
      Range Interactions.
AB  - We study the glass formation in two- and three-dimensional Ising and Heisenberg
      spin systems subject to competing interactions and uniaxial anisotropy with a
      mean-field approach. In three dimensions, for sufficiently strong anisotropy the
      systems always modulate in a striped phase. Below a critical strength of the
      anisotropy, a glassy phase exists in a finite range of temperature, and it
      becomes more stable as the system becomes more isotropic. In two dimensions the
      criticality is always avoided and the glassy phase always exists.

PMID- 27715082
TI  - Exact Bethe Ansatz Spectrum of a Tight-Binding Chain with Dephasing Noise.
AB  - We construct an exact map between a tight-binding model on any bipartite lattice
      in the presence of dephasing noise and a Hubbard model with imaginary interaction
      strength. In one dimension, the exact many-body Liouvillian spectrum can be
      obtained by application of the Bethe ansatz method. We find that both the
      nonequilibrium steady state and the leading decay modes describing the relaxation
      at late times are related to the eta-pairing symmetry of the Hubbard model. We
      show that there is a remarkable relation between the time evolution of an
      arbitrary k-point correlation function in the dissipative system and k-particle
      states of the corresponding Hubbard model.

PMID- 27715083
TI  - Schmalbuch et al. Reply.

PMID- 27715084
TI  - Coherent Backscattering of Light Off One-Dimensional Atomic Strings.
AB  - We present the first experimental realization of coherent Bragg scattering off a
      one-dimensional system-two strings of atoms strongly coupled to a single photonic
      mode-realized by trapping atoms in the evanescent field of a tapered optical
      fiber, which also guides the probe light. We report nearly 12% power reflection
      from strings containing only about 1000 cesium atoms, an enhancement of 2 orders
      of magnitude compared to reflection from randomly positioned atoms. This result
      paves the road towards collective strong coupling in 1D atom-photon systems. Our
      approach also allows for a straightforward fiber connection between several
      distant 1D atomic crystals.

PMID- 27715085
TI  - Global Optimization, Local Adaptation, and the Role of Growth in Distribution
      Networks.
AB  - Highly optimized complex transport networks serve crucial functions in many man
      made and natural systems such as power grids and plant or animal vasculature.
      Often, the relevant optimization functional is nonconvex and characterized by
      many local extrema. In general, finding the global, or nearly global optimum is
      difficult. In biological systems, it is believed that such an optimal state is
      slowly achieved through natural selection. However, general coarse grained models
      for flow networks with local positive feedback rules for the vessel conductivity
      typically get trapped in low efficiency, local minima. In this work we show how
      the growth of the underlying tissue, coupled to the dynamical equations for
      network development, can drive the system to a dramatically improved optimal
      state. This general model provides a surprisingly simple explanation for the
      appearance of highly optimized transport networks in biology such as leaf and
      animal vasculature.

PMID- 27715086
TI  - Controlling Nonsequential Double Ionization in Two-Color Circularly Polarized
      Femtosecond Laser Fields.
AB  - Atoms undergoing strong-field ionization in two-color circularly polarized
      femtosecond laser fields exhibit unique two-dimensional photoelectron
      trajectories and can emit bright circularly polarized extreme ultraviolet and
      soft-x-ray beams. In this Letter, we present the first experimental observation
      of nonsequential double ionization in these tailored laser fields. Moreover, we
      can enhance or suppress nonsequential double ionization by changing the intensity
      ratio and helicity of the two driving laser fields to maximize or minimize high
      energy electron-ion rescattering. Our experimental results are explained through
      classical simulations, which also provide insight into how to optimize the
      generation of circularly polarized high harmonic beams.

PMID- 27715087
TI  - Deformation Behavior across the Zircon-Scheelite Phase Transition.
AB  - The pressure effects on plastic deformation and phase transformation mechanisms
      of materials are of great importance to both Earth science and technological
      applications. Zircon-type materials are abundant in both nature and the
      industrial field; however, there is still no in situ study of their deformation
      behavior. Here, by employing radial x-ray diffraction in a diamond anvil cell, we
      investigate the dislocation-induced texture evolution of zircon-type gadolinium
      vanadate (GdVO_{4}) in situ under pressure and across its phase transitions to
      its high-pressure polymorphs. Zircon-type GdVO_{4} develops a (001) compression
      texture associated with dominant slip along ?100?{001} starting from 5 GPa. This
      (001) texture transforms into a (110) texture during the zircon-scheelite phase
      transition. Our observation demonstrates a martensitic mechanism for the zircon
      scheelite transformation. This work will help us understand the local deformation
      history in the upper mantle and transition zone and provides fundamental guidance
      on material design and processing for zircon-type materials.

PMID- 27715088
TI  - How Isotropic is the Universe?
AB  - A fundamental assumption in the standard model of cosmology is that the Universe
      is isotropic on large scales. Breaking this assumption leads to a set of
      solutions to Einstein's field equations, known as Bianchi cosmologies, only a
      subset of which have ever been tested against data. For the first time, we
      consider all degrees of freedom in these solutions to conduct a general test of
      isotropy using cosmic microwave background temperature and polarization data from
      Planck. For the vector mode (associated with vorticity), we obtain a limit on the
      anisotropic expansion of (sigma_{V}/H)_{0}<4.7*10^{-11} (95% C.L.), which is an
      order of magnitude tighter than previous Planck results that used cosmic
      microwave background temperature only. We also place upper limits on other modes
      of anisotropic expansion, with the weakest limit arising from the regular tensor
      mode, (sigma_{T,reg}/H)_{0}<1.0*10^{-6} (95% C.L.). Including all degrees of
      freedom simultaneously for the first time, anisotropic expansion of the Universe
      is strongly disfavored, with odds of 121 000:1 against.

PMID- 27715089
TI  - Towards Efficient Orbital-Dependent Density Functionals for Weak and Strong
      Correlation.
AB  - We present a new paradigm for the design of exchange-correlation functionals in
      density-functional theory. Electron pairs are correlated explicitly by means of
      the recently developed second order Bethe-Goldstone equation (BGE2) approach.
      Here we propose a screened BGE2 (sBGE2) variant that efficiently regulates the
      coupling of a given electron pair. sBGE2 correctly dissociates H_{2} and
      H_{2}^{+}, a problem that has been regarded as a great challenge in density
      functional theory for a long time. The sBGE2 functional is then taken as a
      building block for an orbital-dependent functional, termed ZRPS, which is a
      natural extension of the PBE0 hybrid functional. While worsening the good
      performance of sBGE2 in H_{2} and H_{2}^{+}, ZRPS yields a remarkable and
      consistent improvement over other density functionals across various chemical
      environments from weak to strong correlation.

PMID- 27715090
TI  - Initial Atomic Motion Immediately Following Femtosecond-Laser Excitation in Phase
      Change Materials.
AB  - Despite the fact that phase-change materials are widely used for data storage, no
      consensus exists on the unique mechanism of their ultrafast phase change and its
      accompanied large and rapid optical change. By using the pump-probe observation
      method combining a femtosecond optical laser and an x-ray free-electron laser, we
      substantiate experimentally that, in both GeTe and Ge_{2}Sb_{2}Te_{5} crystals,
      rattling motion of mainly Ge atoms takes place with keeping the off-center
      position just after femtosecond-optical-laser irradiation, which eventually leads
      to a higher symmetry or disordered state. This very initial rattling motion in
      the undistorted lattice can be related to instantaneous optical change due to the
      loss of resonant bonding that characterizes GeTe-based phase change materials.
      Based on the amorphous structure derived by first-principles molecular dynamics
      simulation, we infer a plausible ultrafast amorphization mechanism via
      nonmelting.

PMID- 27715091
TI  - Triple-Resonant Brillouin Light Scattering in Magneto-Optical Cavities.
AB  - An enhancement in Brillouin light scattering of optical photons with magnons is
      demonstrated in magneto-optical whispering gallery mode resonators tuned to a
      triple-resonance point. This occurs when both the input and output optical modes
      are resonant with those of the whispering gallery resonator, with a separation
      given by the ferromagnetic resonance frequency. The identification and excitation
      of specific optical modes allows us to gain a clear understanding of the mode
      matching conditions. A selection rule due to wave vector matching leads to an
      intrinsic single-sideband excitation. Strong suppression of one sideband is
      essential for one-to-one frequency mapping in coherent optical-to-microwave
      conversion.

PMID- 27715092
TI  - Pointlike Inclusion Interactions in Tubular Membranes.
AB  - Membrane tubes and tubular networks are ubiquitous in living cells. Inclusions
      like proteins are vital for both the stability and the dynamics of such networks.
      These inclusions interact via the curvature deformations they impose on the
      membrane. We analytically study the resulting membrane mediated interactions in
      strongly curved tubular membranes. We model inclusions as constraints coupled to
      the curvature tensor of the membrane tube. First, as special test cases, we
      analyze the interaction between ring- and rod-shaped inclusions. Using Monte
      Carlo simulations, we further show how pointlike inclusions interact to form
      linear aggregates. To minimize the curvature energy of the membrane, inclusions
      self-assemble into either line- or ringlike patterns. Our results show that the
      global curvature of the membrane strongly affects the interactions between
      proteins embedded in it, and can lead to the spontaneous formation of
      biologically relevant structures.

PMID- 27715093
TI  - Nonsequential Double Ionization by Counterrotating Circularly Polarized Two-Color
      Laser Fields.
AB  - We report on nonsequential double ionization of Ar by a laser pulse consisting of
      two counterrotating circularly polarized fields (390 and 780 nm). The double
      ionization probability depends strongly on the relative intensity of the two
      fields and shows a kneelike structure as a function of intensity. We conclude
      that double ionization is driven by a beam of nearly monoenergetic recolliding
      electrons, which can be controlled in intensity and energy by the field
      parameters. The electron momentum distributions show the recolliding electron as
      well as a second electron which escapes from an intermediate excited state of
      Ar^{+}.

PMID- 27715094
TI  - Signatures of Quantum Coherences in Rydberg Excitons.
AB  - Coherent optical control of individual particles has been demonstrated both for
      atoms and semiconductor quantum dots. Here we demonstrate the emergence of
      quantum coherent effects in semiconductor Rydberg excitons in bulk Cu_{2}O.
      Because of the spectral proximity between two adjacent Rydberg exciton states, a
      single-frequency laser may pump both resonances with little dissipation from the
      detuning. As a consequence, additional resonances appear in the absorption
      spectrum that correspond to dressed states consisting of two Rydberg exciton
      levels coupled to the excitonic vacuum, forming a V-type three-level system, but
      driven only by one laser light source. We show that the level of pure dephasing
      in this system is extremely low. These observations are a crucial step towards
      coherently controlled quantum technologies in a bulk semiconductor.

PMID- 27715095
TI  - Evidence of Toroidally Localized Turbulence with Applied 3D Fields in the DIII-D
      Tokamak.
AB  - New evidence indicates that there is significant 3D variation in density
      fluctuations near the boundary of weakly 3D tokamak plasmas when resonant
      magnetic perturbations are applied to suppress transient edge instabilities. The
      increase in fluctuations is concomitant with an increase in the measured density
      gradient, suggesting that this toroidally localized gradient increase could be a
      mechanism for turbulence destabilization in localized flux tubes. Two-fluid
      magnetohydrodynamic simulations find that, although changes to the magnetic field
      topology are small, there is a significant 3D variation of the density gradient
      within the flux surfaces that is extended along field lines. This modeling agrees
      qualitatively with the measurements. The observed gradient and fluctuation
      asymmetries are proposed as a mechanism by which global profile gradients in the
      pedestal could be relaxed due to a local change in the 3D equilibrium. These
      processes may play an important role in pedestal and scrape-off layer transport
      in ITER and other future tokamak devices with small applied 3D fields.

PMID- 27715096
TI  - Stress Singularities in Swelling Soft Solids.
AB  - When a swelling soft solid is rigidly constrained on all sides except for a
      circular opening, it will bulge out to expand as observed during decompressive
      craniectomy, a surgical procedure used to reduce stresses in swollen brains.
      While the elastic energy of the solid decreases throughout this process, large
      stresses develop close to the opening. At the point of contact, the stresses
      exhibit a singularity similar to the ones found in the classic punch indentation
      problem. Here, we study the stresses generated by swelling and the evolution of
      the bulging shape associated with this process. We also consider the possibility
      of damage triggered by zones of either high shear stresses or high fiber
      stretches.

PMID- 27715097
TI  - Improved Error Thresholds for Measurement-Free Error Correction.
AB  - Motivated by limitations and capabilities of neutral atom qubits, we examine
      whether measurement-free error correction can produce practical error thresholds.
      We show that this can be achieved by extracting redundant syndrome information,
      giving our procedure extra fault tolerance and eliminating the need for ancilla
      verification. The procedure is particularly favorable when multiqubit gates are
      available for the correction step. Simulations of the bit-flip, Bacon-Shor, and
      Steane codes indicate that coherent error correction can produce threshold error
      rates that are on the order of 10^{-3} to 10^{-4}-comparable with or better than
      measurement-based values, and much better than previous results for other
      coherent error correction schemes. This indicates that coherent error correction
      is worthy of serious consideration for achieving protected logical qubits.

PMID- 27715098
TI  - Machine Learning Energies of 2 Million Elpasolite (ABC_{2}D_{6}) Crystals.
AB  - Elpasolite is the predominant quaternary crystal structure (AlNaK_{2}F_{6}
      prototype) reported in the Inorganic Crystal Structure Database. We develop a
      machine learning model to calculate density functional theory quality formation
      energies of all ~2*10^{6} pristine ABC_{2}D_{6} elpasolite crystals that can be
      made up from main-group elements (up to bismuth). Our model's accuracy can be
      improved systematically, reaching a mean absolute error of 0.1  eV/atom for a
      training set consisting of 10*10^{3} crystals. Important bonding trends are
      revealed: fluoride is best suited to fit the coordination of the D site, which
      lowers the formation energy whereas the opposite is found for carbon. The bonding
      contribution of the elements A and B is very small on average. Low formation
      energies result from A and B being late elements from group II, C being a late
      (group I) element, and D being fluoride. Out of 2*10^{6} crystals, 90 unique
      structures are predicted to be on the convex hull-among which is NFAl_{2}Ca_{6},
      with a peculiar stoichiometry and a negative atomic oxidation state for Al.

PMID- 27715099
TI  - Quantum-Enhanced Machine Learning.
AB  - The emerging field of quantum machine learning has the potential to substantially
      aid in the problems and scope of artificial intelligence. This is only enhanced
      by recent successes in the field of classical machine learning. In this work we
      propose an approach for the systematic treatment of machine learning, from the
      perspective of quantum information. Our approach is general and covers all three
      main branches of machine learning: supervised, unsupervised, and reinforcement
      learning. While quantum improvements in supervised and unsupervised learning have
      been reported, reinforcement learning has received much less attention. Within
      our approach, we tackle the problem of quantum enhancements in reinforcement
      learning as well, and propose a systematic scheme for providing improvements. As
      an example, we show that quadratic improvements in learning efficiency, and
      exponential improvements in performance over limited time periods, can be
      obtained for a broad class of learning problems.

PMID- 27715100
TI  - Correlation-Enhanced Odd-Parity Interorbital Singlet Pairing in the Iron-Pnictide
      Superconductor LiFeAs.
AB  - The rich variety of iron-based superconductors and their complex electronic
      structure lead to a wide range of possibilities for gap symmetry and pairing
      components. Here we solve in the two-Fe Brillouin zone the full frequency
      dependent linearized Eliashberg equations to investigate spin-fluctuations
      mediated Cooper pairing for LiFeAs. The magnetic excitations are calculated with
      the random phase approximation on a correlated electronic structure obtained with
      density functional theory and dynamical mean field theory. The interaction
      between electrons through Hund's coupling promotes both the intraorbital
      d_{xz(yz)} and the interorbital magnetic susceptibility. As a consequence, the
      leading pairing channel, conventional s^{+-}, acquires sizable interorbital
      d_{xy}-d_{xz(yz)} singlet pairing with odd parity under glide-plane symmetry. The
      combination of intra- and interorbital components makes the results consistent
      with available experiments on the angular dependence of the gaps observed on the
      different Fermi surfaces.

PMID- 27715101
TI  - Thermodynamics versus Local Density Fluctuations in the Metal-Mott-Insulator
      Crossover.
AB  - The crossover between a metal and a Mott insulator leads to a localization of
      fermions from delocalized Bloch states to localized states. We experimentally
      study this crossover using fermionic atoms in an optical lattice by measuring
      thermodynamic and local (on-site) density correlations. In the metallic phase at
      incommensurable filling we observe the violation of the local fluctuation
      dissipation theorem indicating that the thermodynamics of the system cannot be
      characterized by local observables alone. In contrast, in the Mott insulator we
      observe the convergence of local and thermodynamic fluctuations indicating the
      absence of long-range density-density correlations.

PMID- 27715102
TI  - Double-Core-Hole States in Neon: Lifetime, Post-Collision Interaction, and
      Spectral Assignment.
AB  - Using synchrotron radiation and high-resolution electron spectroscopy, we have
      directly observed and identified specific photoelectrons from K^{-2}V states in
      neon corresponding to simultaneous 1s ionization and 1s->valence excitation. The
      natural lifetime broadening of the K^{-2}V states and the relative intensities of
      different types of shakeup channels have been determined experimentally and
      compared to ab initio calculations. Moreover, the high-energy Auger spectrum
      resulting from the decay of Ne^{2+}K^{-2} and Ne^{+}K^{-2}V states as well as
      from participator Auger decay from Ne^{+}K^{-1}L^{-1}V states, has been measured
      and assigned in detail utilizing the characteristic differences in lifetime
      broadenings of these core hole states. Furthermore, post collision interaction
      broadening of Auger peaks is clearly observed only in the hypersatellite spectrum
      from K^{-2} states, due to the energy sharing between the two 1s photoelectrons
      which favors the emission of one slow and one fast electron.

PMID- 27715103
TI  - Z_{2} and Chiral Anomalies in Topological Dirac Semimetals.
AB  - We demonstrate that topological Dirac semimetals, which possess two Dirac nodes,
      separated in momentum space along a rotation axis and protected by rotational
      symmetry, exhibit an additional quantum anomaly, distinct from the chiral
      anomaly. This anomaly, which we call the Z_{2} anomaly, is a consequence of the
      fact that the Dirac nodes in topological Dirac semimetals carry a Z_{2}
      topological charge. The Z_{2} anomaly refers to nonconservation of this charge in
      the presence of external fields due to quantum effects and has observable
      consequences due to its interplay with the chiral anomaly. We discuss possible
      implications of this for the interpretation of magnetotransport experiments on
      topological Dirac semimetals. We also provide a possible explanation for the
      magnetic field dependent angular narrowing of the negative longitudinal
      magnetoresistance, observed in a recent experiment on Na_{3}Bi.

PMID- 27715104
TI  - Necessary Condition for Emergent Symmetry from the Conformal Bootstrap.
AB  - We use the conformal bootstrap program to derive the necessary conditions for
      emergent symmetry enhancement from discrete symmetry (e.g., Z_{n}) to continuous
      symmetry [e.g., U(1)] under the renormalization group flow. In three dimensions,
      in order for Z_{2} symmetry to be enhanced to U(1) symmetry, the conformal
      bootstrap program predicts that the scaling dimension of the order parameter
      field at the infrared conformal fixed point must satisfy Delta_{1}>1.08. We also
      obtain the similar necessary conditions for Z_{3} symmetry with Delta_{1}>0.580
      and Z_{4} symmetry with Delta_{1}>0.504 from the simultaneous conformal bootstrap
      analysis of multiple four-point functions. As applications, we show that our
      necessary conditions impose severe constraints on the nature of the chiral phase
      transition in QCD, the deconfinement criticality in Neel valence bond solid
      transitions, and anisotropic deformations in critical O(n) models. We prove that
      some fixed points proposed in the literature are unstable under the perturbation
      that cannot be forbidden by the discrete symmetry. In these situations, the
      second-order phase transition with enhanced symmetry cannot happen.

PMID- 27715105
TI  - Thermodynamics of Accelerating Black Holes.
AB  - We address a long-standing problem of describing the thermodynamics of an
      accelerating black hole. We derive a standard first law of black hole
      thermodynamics, with the usual identification of entropy proportional to the area
      of the event horizon-even though the event horizon contains a conical
      singularity. This result not only extends the applicability of black hole
      thermodynamics to realms previously not anticipated, it also opens a possibility
      for studying novel properties of an important class of exact radiative solutions
      of Einstein equations describing accelerated objects. We discuss the
      thermodynamic volume, stability, and phase structure of these black holes.

PMID- 27715106
TI  - Ultrafast Spin Density Wave Transition in Chromium Governed by Thermalized
      Electron Gas.
AB  - The energy and momentum selectivity of time- and angle-resolved photoemission
      spectroscopy is exploited to address the ultrafast dynamics of the
      antiferromagnetic spin density wave (SDW) transition photoexcited in epitaxial
      thin films of chromium. We are able to quantitatively extract the evolution of
      the SDW order parameter Delta through the ultrafast phase transition and show
      that Delta is governed by the transient temperature of the thermalized electron
      gas, in a mean field description. The complete destruction of SDW order on a sub
      100 fs time scale is observed, much faster than for conventional charge density
      wave materials. Our results reveal that equilibrium concepts for phase
      transitions such as the order parameter may be utilized even in the strongly
      nonadiabatic regime of ultrafast photoexcitation.

PMID- 27715107
TI  - Fate of Spinons at the Mott Point.
AB  - Gapless spin liquids have recently been observed in several frustrated Mott
      insulators, with elementary spin excitations-"spinons"-reminiscent of degenerate
      Fermi systems. However, their precise role at the Mott point, where charge
      fluctuations begin to proliferate, remains controversial and ill understood. Here
      we present the simplest theoretical framework that treats the dynamics of
      emergent spin and charge excitations on the same footing, providing a new
      physical picture of the Mott metal-to-insulator transition at half filing. We
      identify a generic orthogonality mechanism leading to strong damping of spinons,
      arising as soon as the Mott gap closes. Our results indicate that spinons should
      not play a significant role within the high-temperature quantum critical regime
      above the Mott point-in striking agreement with all available experiments.

PMID- 27715108
TI  - Publisher's Note: Glassy Dynamics in Disordered Electronic Systems Reveal
      Striking Thermal Memory Effects [Phys. Rev. Lett. 117, 116601 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.117.116601.

PMID- 27715111
TI  - Shocks in the Early Universe.
AB  - We point out a surprising consequence of the usually assumed initial conditions
      for cosmological perturbations. Namely, a spectrum of Gaussian, linear,
      adiabatic, scalar, growing mode perturbations not only creates acoustic
      oscillations of the kind observed on very large scales today, it also leads to
      the production of shocks in the radiation fluid of the very early Universe.
      Shocks cause departures from local thermal equilibrium as well as create
      vorticity and gravitational waves. For a scale-invariant spectrum and standard
      model physics, shocks form for temperatures 1  GeV<T<10^{7}  GeV. For more
      general power spectra, such as have been invoked to form primordial black holes,
      shock formation and the consequent gravitational wave emission provide a signal
      detectable by current and planned gravitational wave experiments, allowing them
      to strongly constrain conditions present in the primordial Universe as early as
      10^{-30}  sec after the big bang.

PMID- 27715109
TI  - Magneto-Optical Signature of Massless Kane Electrons in Cd_{3}As_{2}.
AB  - We report on optical reflectivity experiments performed on Cd_{3}As_{2} over a
      broad range of photon energies and magnetic fields. The observed response clearly
      indicates the presence of 3D massless charge carriers. The specific cyclotron
      resonance absorption in the quantum limit implies that we are probing massless
      Kane electrons rather than symmetry-protected 3D Dirac particles. The latter may
      appear at a smaller energy scale and are not directly observed in our infrared
      experiments.

PMID- 27715110
TI  - Universal Scaling of Robust Thermal Hot Spot and Ionic Current Enhancement by
      Focused Ohmic Heating in a Conic Nanopore.
AB  - A stable nanoscale thermal hot spot, with temperature approaching 100  degrees C,
      is shown to be sustained by localized Ohmic heating of a focused electric field
      at the tip of a slender conic nanopore. The self-similar (length-independent)
      conic geometry allows us to match the singular heat source at the tip to the
      singular radial heat loss from the slender cone to obtain a self-similar steady
      temperature profile along the cone and the resulting ionic current conductance
      enhancement due to viscosity reduction. The universal scaling, which depends only
      on a single dimensionless parameter Z, collapses the measured conductance data
      and computed temperature profiles in ion-track conic nanopores and conic
      nanopipettes. The collapsed numerical data reveal universal values for the hot
      spot location and temperature in an aqueous electrolyte.

PMID- 27715112
TI  - Ab Initio Theory of Coherent Laser-Induced Magnetization in Metals.
AB  - We present the first materials specific ab initio theory of the magnetization
      induced by circularly polarized laser light in metals. Our calculations are based
      on nonlinear density matrix theory and include the effect of absorption. We show
      that the induced magnetization, commonly referred to as inverse Faraday effect,
      is strongly materials and frequency dependent, and demonstrate the existence of
      both spin and orbital induced magnetizations which exhibit a surprisingly
      different behavior. We show that for nonmagnetic metals (such as Cu, Au, Pd, Pt)
      and antiferromagnetic metals the induced magnetization is antisymmetric in the
      light's helicity, whereas for ferromagnetic metals (Fe, Co, Ni, FePt) the
      imparted magnetization is only asymmetric in the helicity. We compute effective
      optomagnetic fields that correspond to the induced magnetizations and provide
      guidelines for achieving all-optical helicity-dependent switching.

PMID- 27715113
TI  - Callan-Jones et al. Reply.

PMID- 27715114
TI  - Revealing Three-Dimensional Structure of an Individual Colloidal Crystal Grain by
      Coherent X-Ray Diffractive Imaging.
AB  - We present results of a coherent x-ray diffractive imaging experiment performed
      on a single colloidal crystal grain. The full three-dimensional (3D) reciprocal
      space map measured by an azimuthal rotational scan contained several orders of
      Bragg reflections together with the coherent interference signal between them.
      Applying the iterative phase retrieval approach, the 3D structure of the crystal
      grain was reconstructed and positions of individual colloidal particles were
      resolved. As a result, an exact stacking sequence of hexagonal close-packed
      layers including planar and linear defects were identified.

PMID- 27715115
TI  - Comment on "Two-Dimensional Optical Control of Electron Spin Orientation by
      Linearly Polarized Light in InGaAs".

PMID- 27715116
TI  - Determination of the Nonequilibrium Steady State Emerging from a Defect.
AB  - We consider the nonequilibrium time evolution of a translationally invariant
      state under a Hamiltonian with a localized defect. We discern the situations
      where a light cone spreads out from the defect and separates the system into
      regions with macroscopically different properties. We identify the light cone and
      propose a procedure to obtain a (quasi)stationary state describing the late time
      dynamics of local observables. As an explicit example, we study the time
      evolution generated by the Hamiltonian of the transverse-field Ising chain with a
      local defect that cuts the interaction between two sites (a quench of the
      boundary conditions alongside a global quench). We solve the dynamics exactly and
      show that the late time properties can be obtained with the general method
      proposed.

PMID- 27715118
TI  - Spin-Orbit Twisted Spin Waves: Group Velocity Control.
AB  - We present a theoretical and experimental study of the interplay between spin
      orbit coupling (SOC), Coulomb interaction, and motion of conduction electrons in
      a magnetized two-dimensional electron gas. Via a transformation of the many-body
      Hamiltonian we introduce the concept of spin-orbit twisted spin waves, whose
      energy dispersions and damping rates are obtained by a simple wave-vector shift
      of the spin waves without SOC. These theoretical predictions are validated by
      Raman scattering measurements. With optical gating of the density, we vary the
      strength of the SOC to alter the group velocity of the spin wave. The findings
      presented here differ from that of spin systems subject to the Dzyaloshinskii
      Moriya interaction. Our results pave the way for novel applications in spin-wave
      routing devices and for the realization of lenses for spin waves.

PMID- 27715117
TI  - Insight into the Narrow Structure in eta Photoproduction on the Neutron from
      Helicity-Dependent Cross Sections.
AB  - The double polarization observable E and the helicity dependent cross sections
      sigma_{1/2} and sigma_{3/2} were measured for eta photoproduction from quasifree
      protons and neutrons. The circularly polarized tagged photon beam of the A2
      experiment at the Mainz MAMI accelerator was used in combination with a
      longitudinally polarized deuterated butanol target. The almost 4pi detector setup
      of the Crystal Ball and TAPS is ideally suited to detect the recoil nucleons and
      the decay photons from eta->2gamma and eta->3pi^{0}. The results show that the
      narrow structure previously observed in eta photoproduction from the neutron is
      only apparent in sigma_{1/2} and hence, most likely related to a spin-1/2
      amplitude. Nucleon resonances that contribute to this partial wave in eta
      production are only N 1/2^{-} (S_{11}) and N 1/2^{+} (P_{11}). Furthermore, the
      extracted Legendre coefficients of the angular distributions for sigma_{1/2} are
      in good agreement with recent reaction model predictions assuming a narrow
      resonance in the P_{11} wave as the origin of this structure.

PMID- 27715119
TI  - Spatiotemporal Wave Front Shaping in a Microwave Cavity.
AB  - Controlling waves in complex media has become a major topic of interest, notably
      through the concepts of time reversal and wave front shaping. Recently, it was
      shown that spatial light modulators can counterintuitively focus waves both in
      space and time through multiple scattering media when illuminated with optical
      pulses. In this Letter, we transpose the concept to a microwave cavity using flat
      arrays of electronically tunable resonators. We prove that maximizing the Green's
      function between two antennas at a chosen time yields diffraction limited
      spatiotemporal focusing. Then, changing the photons' dwell time inside the
      cavity, we modify the relative distribution of the spatial and temporal degrees
      of freedom (DOF), and we demonstrate that it has no impact on the field
      enhancement: wave front shaping makes use of all available DOF, irrespective of
      their spatial or temporal nature. Our results prove that wave front shaping using
      simple electronically reconfigurable arrays of reflectors is a viable approach to
      the spatiotemporal control of microwaves, with potential applications in medical
      imaging, therapy, telecommunications, radar, or sensing. They also offer new
      fundamental insights regarding the coupling of spatial and temporal DOF in
      complex media.

PMID- 27715120
TI  - Comment on "Cortical Flow-Driven Shapes of Nonadherent Cells".

PMID- 27715121
TI  - Large Bragg Reflection from One-Dimensional Chains of Trapped Atoms Near a
      Nanoscale Waveguide.
AB  - We report experimental observations of a large Bragg reflection from arrays of
      cold atoms trapped near a one-dimensional nanoscale waveguide. By using an
      optical lattice in the evanescent field surrounding a nanofiber with a period
      nearly commensurate with the resonant wavelength, we observe a reflectance of up
      to 75% for the guided mode. Each atom behaves as a partially reflecting mirror
      and an ordered chain of about 2000 atoms is sufficient to realize an efficient
      Bragg mirror. Measurements of the reflection spectra as a function of the lattice
      period and the probe polarization are reported. The latter shows the effect of
      the chiral character of nanoscale waveguides on this reflection. The ability to
      control photon transport in 1D waveguides coupled to spin systems would enable
      novel quantum network capabilities and the study of many-body effects emerging
      from long-range interactions.

PMID- 27715122
TI  - Persistent Directional Current at Equilibrium in Nonreciprocal Many-Body Near
      Field Electromagnetic Heat Transfer.
AB  - We consider the consequence of nonreciprocity in near-field heat transfer by
      studying systems consisting of magneto-optical nanoparticles. We demonstrate
      that, in thermal equilibrium, a nonreciprocal many-body system in heat transfer
      can support a persistent directional heat current, without violating the second
      law of thermodynamics. Such a persistent directional heat current cannot occur in
      reciprocal systems, and can only arise in many-body systems in heat transfer. The
      use of nonreciprocity therefore points to a new regime of near-field heat
      transfer for the control of heat flow in the nanoscale.

PMID- 27715123
TI  - Spin-Orbit-Coupled Correlated Metal Phase in Kondo Lattices: An Implementation
      with Alkaline-Earth Atoms.
AB  - We show that an interplay between quantum effects, strong on-site ferromagnetic
      exchange interaction, and antiferromagnetic correlations in Kondo lattices can
      give rise to an exotic spin-orbit coupled metallic state in regimes where
      classical treatments predict a trivial insulating behavior. This phenomenon can
      be simulated with ultracold alkaline-earth fermionic atoms subject to a laser
      induced magnetic field by observing dynamics of spin-charge excitations in quench
      experiments.

PMID- 27715124
TI  - Universal Scaling Laws for Dense Particle Suspensions in Turbulent Wall-Bounded
      Flows.
AB  - The macroscopic behavior of dense suspensions of neutrally buoyant spheres in
      turbulent plane channel flow is examined. We show that particles larger than the
      smallest turbulence scales cause the suspension to deviate from the continuum
      limit in which its dynamics is well described by an effective suspension
      viscosity. This deviation is caused by the formation of a particle layer close to
      the wall with significant slip velocity. By assuming two distinct transport
      mechanisms in the near-wall layer and the turbulence in the bulk, we define an
      effective wall location such that the flow in the bulk can still be accurately
      described by an effective suspension viscosity. We thus propose scaling laws for
      the mean velocity profile of the suspension flow, together with a master equation
      able to predict the increase in drag as a function of the particle size and
      volume fraction.

PMID- 27715125
TI  - Extended Propagation of Powerful Laser Pulses in Focusing Kerr Media.
AB  - Powerful incoherent laser pulses can propagate in focusing Kerr media much longer
      distances than can coherent pulses, due to the fast phase mixing that prevents
      transverse filamentation. This distance is limited by 4-wave scattering, which
      accumulates waves at small transverse wave numbers, where phase mixing is too
      slow to retain the incoherence and thus prevent the filamentation. However, we
      identify how this theoretical limit can be overcome by countering this
      accumulation through transverse heating of the pulse by random fluctuations of
      the refractive index. Thus, the laser pulse propagation distances are
      significantly extended, making feasible, in particular, the generation of
      unprecedentedly intense and powerful short laser pulses in a plasma by means of
      backward Raman amplification in new random laser regimes.

PMID- 27715126
TI  - Continuous Quantum Nondemolition Measurement of the Transverse Component of a
      Qubit.
AB  - Quantum jumps of a qubit are usually observed between its energy eigenstates,
      also known as its longitudinal pseudospin component. Is it possible, instead, to
      observe quantum jumps between the transverse superpositions of these eigenstates?
      We answer positively by presenting the first continuous quantum nondemolition
      measurement of the transverse component of an individual qubit. In a circuit QED
      system irradiated by two pump tones, we engineer an effective Hamiltonian whose
      eigenstates are the transverse qubit states, and a dispersive measurement of the
      corresponding operator. Such transverse component measurements are a useful tool
      in the driven-dissipative operation engineering toolbox, which is central to
      quantum simulation and quantum error correction.

PMID- 27715127
TI  - Entanglement of Distillation for Lattice Gauge Theories.
AB  - We study the entanglement structure of lattice gauge theories from the local
      operational point of view, and, similar to Soni and Trivedi [J. High Energy Phys.
      1 (2016) 1], we show that the usual entanglement entropy for a spatial
      bipartition can be written as the sum of an undistillable gauge part and of
      another part corresponding to the local operations and classical communication
      distillable entanglement, which is obtained by depolarizing the local
      superselection sectors. We demonstrate that the distillable entanglement is zero
      for pure Abelian gauge theories at zero gauge coupling, while it is in general
      nonzero for the non-Abelian case. We also consider gauge theories with matter,
      and show in a perturbative approach how area laws-including a topological
      correction-emerge for the distillable entanglement. Finally, we also discuss the
      entanglement entropy of gauge fixed states and show that it has no relation to
      the physical distillable entropy.

PMID- 27715128
TI  - Symmetry and Size of Membrane Protein Polyhedral Nanoparticles.
AB  - In recent experiments [T. Basta et al., Proc. Natl. Acad. Sci. U.S.A. 111, 670
      (2014)] lipids and membrane proteins were observed to self-assemble into membrane
      protein polyhedral nanoparticles (MPPNs) with a well-defined polyhedral protein
      arrangement and characteristic size. We develop a model of MPPN self-assembly in
      which the preferred symmetry and size of MPPNs emerge from the interplay of
      protein-induced lipid bilayer deformations, topological defects in protein
      packing, and thermal effects. With all model parameters determined directly from
      experiments, our model correctly predicts the observed symmetry and size of
      MPPNs. Our model suggests how key lipid and protein properties can be modified to
      produce a range of MPPN symmetries and sizes in experiments.

PMID- 27715129
TI  - Superionic-Superionic Phase Transitions in Body-Centered Cubic H_{2}O Ice.
AB  - From first-principles molecular dynamics, we investigate the relation between the
      superionic proton conduction and the behavior of the O?H?O bond (ice VII^{'} to
      ice X transition) in body-centered-cubic (bcc) H_{2}O ice between 1300 and 2000 K
      and up to 300 GPa. We bring evidence that there are three distinct phases in the
      superionic bcc stability field. A first superionic phase characterized by
      extremely fast diffusion of highly delocalized protons (denoted VII^{''} 
      hereinafter) is stable at low pressures. A first-order transition separates this
      phase from a superionic VII^{'}, characterized by a finite degree of localization
      of protons along the nonsymmetric O?H?O bonds. The transition is identified in
      structural, energetic, and elastic analysis. Upon further compression a second
      order phase transition leads to the superionic ice X with symmetric O?H?O bonds.

PMID- 27715130
TI  - Simultaneous Precision Gravimetry and Magnetic Gradiometry with a Bose-Einstein
      Condensate: A High Precision, Quantum Sensor.
AB  - A Bose-Einstein condensate is used as an atomic source for a high precision
      sensor. A 5*10^{6}  atom F=1 spinor condensate of ^{87}Rb is released into free
      fall for up to 750 ms and probed with a T=130  ms Mach-Zehnder atom
      interferometer based on Bragg transitions. The Bragg interferometer
      simultaneously addresses the three magnetic states |m_{f}=1,0,-1?, facilitating a
      simultaneous measurement of the acceleration due to gravity with a 1000 run
      precision of Deltag/g=1.45*10^{-9} and the magnetic field gradient to a precision
      of 120  pT/m.

PMID- 27715131
TI  - Illuminating Molecular Symmetries with Bicircular High-Order-Harmonic Generation.
AB  - We present a general theory of bicircular high-order-harmonic generation from N
      fold rotationally symmetric molecules. Using a rotating frame of reference we
      predict the complete structure of the high-order-harmonic spectra for arbitrary
      driving frequency ratios and show how molecular symmetries can be directly
      identified from the harmonic signal. Our findings reveal that a characteristic
      fingerprint of rotational molecular symmetries can be universally observed in the
      ultrafast response of molecules to strong bicircular fields.

PMID- 27715132
TI  - Lateral Electron Confinement with Open Boundaries: Quantum Well States above
      Nanocavities at Pb(111).
AB  - We have studied electron states present at the Pb(111) surface above Ar-filled
      nanocavities created by ion beam irradiation and annealing. Vertical confinement
      between the parallel crystal and nanocavity surfaces creates a series of quantum
      well state subbands. Differential conductance data measured by scanning tunneling
      spectroscopy contain a characteristic spectroscopic fine structure within the
      highest occupied subband, revealing additional quantization. Unexpectedly,
      reflection at the open boundary where the thin Pb film recovers its bulk
      thickness gives rise to the lateral confinement of electrons.

PMID- 27715133
TI  - Bosonic Analogue of Dirac Composite Fermi Liquid.
AB  - We introduce a particle-hole-symmetric metallic state of bosons in a magnetic
      field at odd-integer filling. This state hosts composite fermions whose energy
      dispersion features a quadratic band touching and corresponding 2pi Berry flux
      protected by particle-hole and discrete rotation symmetries. We also construct an
      alternative particle-hole symmetric state-distinct in the presence of inversion
      symmetry-without Berry flux. As in the Dirac composite Fermi liquid introduced by
      Son [Phys. Rev. X 5, 031027 (2015)], breaking particle-hole symmetry recovers the
      familiar Chern-Simons theory. We discuss realizations of this phase both in 2D
      and on bosonic topological insulator surfaces, as well as signatures in
      experiments and simulations.

PMID- 27715134
TI  - Detection of Recurrent Fluorescence Photons.
AB  - We have detected visible photons emitted from the thermally populated electronic
      excited state, namely recurrent fluorescence (RF), of C_{6}^{-} stored in an
      electrostatic ion storage ring. Clear evidence is provided to distinguish RF from
      normal fluorescence, based on the temporal profile of detected photons
      synchronized with the revolution of C_{6}^{-} in the ring, for which the time
      scale is far longer than the lifetime of the intact photoexcited state. The
      relaxation (cooling) process via RF is likely to be commonplace for isolated
      molecular systems and crucial to the stabilization of molecules in interstellar
      environments.

PMID- 27715136
TI  - Quantum Correlations, Separability, and Quantum Coherence Length in Equilibrium
      Many-Body Systems.
AB  - Nonlocality is a fundamental trait of quantum many-body systems, both at the
      level of pure states, as well as at the level of mixed states. Because of
      nonlocality, mixed states of any two subsystems are correlated in a stronger way
      than what can be accounted for by considering the correlated probabilities of
      occupying some microstates. In the case of equilibrium mixed states, we
      explicitly build two-point quantum correlation functions, which capture the
      specific, superior correlations of quantum systems at finite temperature, and
      which are directly accessible to experiments when correlating measurable
      properties. When nonvanishing, these correlation functions rule out a precise
      form of separability of the equilibrium state. In particular, we show numerically
      that quantum correlation functions generically exhibit a finite quantum coherence
      length, dictating the characteristic distance over which degrees of freedom
      cannot be considered as separable. This coherence length is completely
      disconnected from the correlation length of the system-as it remains finite even
      when the correlation length of the system diverges at finite temperature-and it
      unveils the unique spatial structure of quantum correlations.

PMID- 27715135
TI  - Nonadditive Compositional Curvature Energetics of Lipid Bilayers.
AB  - The unique properties of the individual lipids that compose biological membranes
      together determine the energetics of the surface. The energetics of the surface,
      in turn, govern the formation of membrane structures and membrane reshaping
      processes, and thus they will underlie cellular-scale models of viral fusion,
      vesicle-dependent transport, and lateral organization relevant to signaling. The
      spontaneous curvature, to the best of our knowledge, is always assumed to be
      additive. We describe observations from simulations of unexpected nonadditive
      compositional curvature energetics of two lipids essential to the plasma
      membrane: sphingomyelin and cholesterol. A model is developed that connects
      molecular interactions to curvature stress, and which explains the role of local
      composition. Cholesterol is shown to lower the number of effective Kuhn segments
      of saturated acyl chains, reducing lateral pressure below the neutral surface of
      bending and favoring positive curvature. The effect is not observed for
      unsaturated (flexible) acyl chains. Likewise, hydrogen bonding between
      sphingomyelin lipids leads to positive curvature, but only at sufficient
      concentration, below which the lipid prefers negative curvature.

PMID- 27715137
TI  - Effect of occlusal plane control procedure on hyoid bone position and pharyngeal
      airway of hyperdivergent skeletal Class II patients.
AB  - OBJECTIVE: To evaluate the effect of occlusal plane control on the hyoid bone
      position and pharyngeal airway of hyperdivergent skeletal Class II patients
      during orthodontic treatment. MATERIALS AND METHODS: Cephalograms of 47
      hyperdivergent skeletal Class II subjects with occlusal plane control (OPC), and
      another 50 subjects without occlusal plane control (NOPC) were selected to
      compare the effects of the occlusal plane control procedure. Lateral cephalograms
      before treatment (T1), immediately after treatment (T2), and an average of 12
      months after treatment (T3) were obtained, and 17 measurements were analyzed in
      each group and compared between groups. RESULTS: With respect to the T2-T1
      changes, the sagittal discrepancies in both groups were alleviated. In the OPC
      group, both the occlusal and mandibular plane angles decreased, accompanied by
      anterior and superior movement and counterclockwise rotation of the hyoid bone.
      The overall changes from T3 to T1 in each group exhibited trends similar to that
      induced by treatment. As for pharyngeal airway space alterations, no significant
      difference in OPC group was presented throughout treatment or retention periods.
      CONCLUSIONS: The customized occlusal plane control procedure was effective for
      hyperdivergent skeletal Class II patients: The occlusal plane rotated
      counterclockwise, followed by a counterclockwise rotation of the mandibular
      plane. The hyoid bone moved anteriorly and superiorly, accompanied by its
      counterclockwise rotation. However, this procedure did not induce significant
      alteration of the pharyngeal airway space.

PMID- 27715138
TI  - Diagnosis and management of lipoedema in the community.
AB  - Lipoedema is a chronic progressive adipose disorder that affects mainly women and
      presents as symmetrical enlargement of the buttocks and legs. It is commonly
      misdiagnosed as obesity or lymphoedema, but careful assessment will reveal a
      disproportionate enlargement below the waist which is resistant to dieting,
      sparing of the feet, legs are tender or painful to touch and bruise easily, there
      is occasional orthostatic oedema, and there is often significant psychological
      morbidity. Lipoedema is a oestrogen-regulated condition with onset around puberty
      in 78% of women, and there is often a strong family history. The condition is
      exacerbated by weight gain and there is increasing anecdotal evidence that women
      who are obese are seeking a diagnosis of lipoedema, either to procure NHS funded
      manual lymphatic drainage, or to medicalise their obesity and avoid acknowledging
      that the responsibility for their weight gain is lifestyle orientated. Management
      of lipoedema consists of accurate diagnosis, psychological care, management of
      orthostatic oedema, and prevention of progression through skin care and weight
      management.

PMID- 27715139
TI  - Chronic Oedema.

PMID- 27715140
TI  - British Lymphology Society update.

PMID- 27715142
TI  - Lymphoedema management at night: views from patients across five countries.
AB  - The aim of this study was to gain a comprehensive insight into the use of night
      time compression in the management of lymphoedema in patients who had been
      suffering from chronic lymphoedema for over 12 months. Data were collected and
      analysed from 94 patients, across five countries. Understanding user
      characteristics provided insight and understanding into how night-time
      compression regimens were initiated, products were used and benefits to the
      patient were reported. In addition to gaining an insight into user habits and
      night-time compression benefits, unmet needs were also identified. Positive
      outcomes from the use of night-time compression were reported, with all patients
      identifying benefits of using night-time compression. An increase in swelling was
      documented in 89% of all patients in this study group when night-time compression
      was not used. The study provided an opportunity to explore how lymphoedema
      affects patients, and how night-time compression can form part of a beneficial
      regime.

PMID- 27715143
TI  - Chronic oedema: its prevalence, effects and management.
AB  - Ageing affects not only individuals but also society. It occurs throughout the
      western world. The ageing process may lead to the development of conditions, such
      as chronic oedema, as well as comorbidities such as osteoarthritis. These
      comorbidities can make the management of chronic oedema even more difficult. This
      is an especially important consideration when tailoring individualised care
      plans, such as exercise, as conditions such as rheumatoid arthritis can limit
      patients' ability to manage their oedema. Despite challenges, education can
      improve patient outcomes when evidence-based practice is used.

PMID- 27715145
TI  - Selecting a compression wrap when treating lymphoedema.

PMID- 27715144
TI  - Lymphoedema management with the LymphFlow Advance pneumatic compression pump.
AB  - There are many intermittent pneumatic compression devices available for use in
      the management and adjunct treatment of lymphatic, venous and arterial disease.
      This article discusses the development of a new advanced pneumatic compression
      device, the LymphFlow Advance, which can perform focussed treatment on the
      lymphoedematous area using a variety of different cycles. Case studies with
      therapist and patient feedback are used to demonstrate the use of the LymphFlow
      Advance in the lymphoedema clinic, with a discussion of the evidence to underpin
      recommended treatment regimes.

PMID- 27715147
TI  - Injury prevention.
AB  - Emergency nurses with an interest in injury prevention can visit the South West
      Public Health Observatory's Injury Profile, which provides a snapshot of
      intentional and unintentional injuries in England by local authority. The website
      presents a series of interactive maps that enables regional and national
      comparisons to be made against about 40 injury-related indicators.

PMID- 27715146
TI  - 64Cu-PSMA-617 PET/CT Imaging of Prostate Adenocarcinoma: First In-Human Studies.
AB  - AIM: The prostate-specific membrane antigen (PSMA) is a cell surface protein,
      which is overexpressed in nearly all cases of prostate cancer (PCa). PET imaging
      with 68Ga-PSMA-HBED-CC has recently found widespread application in the diagnosis
      of recurrent PCa. In this study, the diagnostic potential of 64Cu-labeled PSMA
      ligand (PSMA-617) PET in patients with PCa has been investigated. MATERIALS AND
      METHODS: The study was conducted simultaneously at two nuclear medicine centers,
      Austria (Vienna, Center 1) and Germany (Bad Berka, Center 2). The patients (n =
      29) included in this study were referred for PET (Center 1, 21 patients) or
      PET/CT (Center 2, 8 patients) imaging with either a high suspicion of recurrent
      disease or for possible surgical or PSMA radioligand therapy planning. PET images
      of the whole body were performed at 1 hour p.i. and additional images of the
      pelvis at 2 hours p.i. RESULTS: In 23 of 29 patients, at least one focus of
      pathological tracer uptake suspicious for primary disease in the prostate lobe or
      recurrent disease was detected. Among healthy organs, the salivary glands,
      kidneys, and liver showed the highest radiotracer uptake. Lesions suspicious for
      PCa were detected with excellent contrast as early as 1 hour p.i. with high
      detection rates even at low prostate-specific antigen (PSA) levels. CONCLUSION:
      The preliminary results of this study demonstrate the high potential of 64Cu-PSMA
      ligand PET/CT imaging in patients with recurrent disease and in the primary
      staging of selected patients with progressive local disease. The acquired PET
      images showed an excellent resolution of the detected lesions with very high
      lesion-to- background contrast. Furthermore, the long half-life of 64Cu allows
      distribution of the tracer to clinical PET centers that lack radiochemistry
      facilities for the preparation of 68Ga-PSMA ligand (satellite concept).

PMID- 27715148
TI  - Emergency admissions.
AB  - Ambulatory emergency care may make about one in six emergency admissions
      unnecessary, says the NHS Institute. To help organisations implement the
      appropriate patient pathways, the NHS Institute has a range of resources,
      including an Ambulatory Emergency Care (AEC) network, and a directory of 49
      relevant clinical scenarios and emergency conditions. These and other resources
      can be accessed at http://tinyurl.com/6gt9m9x.

PMID- 27715150
TI  - Infection control.
AB  - A report on an improvement project in which reductions in the contamination of
      blood culture samples led to a lower incidence of healthcare-associated
      infections (HCAIs) in an emergency department has been added to the Foundation of
      Nursing Studies Centre for Nursing Innovation online library.

PMID- 27715149
TI  - Violent assaults.
AB  - The Department of Health is conducting an audit to determine whether emergency
      departments (EDs) collect and share data on violent assaults, and the extent to
      which data sharing has become standard practice. This mandatory ED data-sharing
      audit must be completed by a staff member who understands data collection
      procedures and how the department functions. People who want to take part in the
      audit should access http://tinyurl.com/cm4wuc6.

PMID- 27715151
TI  - E-learning courses.
AB  - Preponline, a social enterprise developed and run by nurses, offers e-learning
      courses on a range of subjects. The courses can be accredited and form part of
      continuing professional development programmes.

PMID- 27715153
TI  - Managing major incidents.
AB  - THIS SUMMER, the eyes of the world will be on our country as we approach the
      start of the Olympic and Paralympic Games. Thousands of visitors will be drawn to
      London and venues nationwide amid hopes of increased revenue from tourism.

PMID- 27715152
TI  - Innovation.
AB  - Shine 2012, the Health Foundation's annual innovation programme, offers
      healthcare teams practical and financial support to extend innovative ideas into
      widespread, evidence-based best practice.

PMID- 27715154
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27715156
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27715155
TI  - Major incident medical management and support: The practical approach at the
      scene Kevin Mackway-Jones Major Incident Medical Management and Support: The
      Practical Approach at the Scene Wiley-Blackwell L41.99 196pp 9781405187572
      1405187573 [Formula: see text].
AB  - ALTHOUGH THIS excellent, informative book is intended primarily to be a manual
      for the pre-major incident medical management and support course, it would be a
      useful resource in any emergency department and a useful guide for individual
      nurses who provide care at major incident scenes.

PMID- 27715157
TI  - Board's eye view.
AB  - MOST HEALTHCARE organisations have major incident plans in place so that they can
      respond quickly to severe or catastrophic events. The Department of Health (DH)
      and the Home Office have adopted a different approach to such events, however, by
      training healthcare staff to help avert them.

PMID- 27715160
TI  - New guidance on antidotes to poison.
AB  - The British Association for Emergency Medicine and Guy's and St Thomas' Poisons
      Unit, London, have published guidance on poison antidotes.

PMID- 27715161
TI  - 'Turf war' alert over ECP proposals.
AB  - Recognising the emergency care practitioner (ECP) role as separate part of the
      nursing profession will cause confusion and trigger 'turf wars' over the division
      of responsibilities, ministers have been warned.

PMID- 27715162
TI  - ?
AB  - No kidding: a major review published last month by the Healthcare Commission
      shows that the ability to meet key elements of the National Service Framework for
      Children, Young People and Maternity Services of more than a quarter of NHS
      trusts in England was 'weak'. The main problems are ensuring that children are
      seen in child friendly environments and providing adequate cover by children's
      nurses.

PMID- 27715163
TI  - ?
AB  - On a knife edge:more than one in ten teenage girls self harm each year, according
      to a study of more than 6,000 school pupils aged 15 and 16 in England.
      Researchers at the universities of Bath and Oxford found that girls are four
      times more likely than boys to have engaged in deliberate self harm, but that
      only 13 per cent of self harming incidents reported by the pupils resulted in
      hospital visits. The study reveals that self cutting, at 65 per cent, was the
      more prevalent form of self harm, followed by self poisoning through overdose, at
      31 per cent. The research is published in By Their Own Young Hand: Deliberate
      self-harm and suicidal ideas in adolescents, published by Jessica Kingsley
      Publishers. See also pages 8-10.

PMID- 27715164
TI  - Nominations sought for ECA committee.
AB  - Members of the RCN Emergency Care Association (ECA) have until September 20 to
      nominate themselves for a place on the association's steering committee.

PMID- 27715165
TI  - Care summaries.
AB  - Patients in Scotland will soon have their own emergency care summaries, health
      minister Andy Kerr announced last month.

PMID- 27715167
TI  - Training package.
AB  - The Health Protection Agency has developed a free online teaching package for
      burns, blasts and major incidents.

PMID- 27715166
TI  - Major changes in minor injuries.
AB  - The NHS is once more undergoing a period of transformation, and life is tough in
      the world of clinical care. Until recently, it was commonly felt that minor
      injury services were undervalued, and some of us are finding our services being
      reduced as primary care trusts (PCTs) struggle to make savings.

PMID- 27715168
TI  - Conference call.
AB  - The RCN minor injuries group is holding its national conference, entitled Minor
      Injury: A matter or urgent care, on January 26 2007 at the Hilton Hotel, Warwick.

PMID- 27715170
TI  - Psychiatric illness.
AB  - Patients with psychiatric illness have long used emergency departments as a first
      point of contact when seeking care.

PMID- 27715169
TI  - Journal scan.
AB  - Abdominal pain is one of the main reasons patients visit emergency departments.

PMID- 27715171
TI  - Board's eye view.
AB  - Current changes in emergency care provision must be accompanied by changes in
      training and education for emergency nurse practitioners, says Kate Ambrose.

PMID- 27715172
TI  - NHS Direct talks.
AB  - Union officials are due to meet health minister Lord Warner this month to discuss
      proposals to cut nearly 600 jobs and close 12 call centres at NHS Direct.

PMID- 27715174
TI  - Erratum.

PMID- 27715173
TI  - APAQ at Thirty.

PMID- 27715175
TI  - Video Modeling to Teach Social-Game Behaviors.

PMID- 27715178
TI  - Coping with grief.
AB  - Every day, road traffic collisions cause death and injury, and emergency care
      staff witness the bloody, tangled bodies of patients and experience the raw
      emotions of patients' relatives.

PMID- 27715179
TI  - The quiet servant.
AB  - Chaplains have been involved in health care for hundreds of years. St
      Bartholomew's Hospital, in London, for example, was founded in 1123 by Rahere, a
      favourite courtier of Henry I who had taken monastic vows and who became the
      first prior of the hospital, managing the monks who cared for its patients.

PMID- 27715177
TI  - Patient expectations of A&E 'bordering on unreasonable'.
AB  - Emergency care staff should have 'more clearly defined powers' to refer on
      patients at triage from A&E, according to health minister Andy Burnham (pictured
      right).

PMID- 27715180
TI  - ?
AB  - Crash course: A&E nurses at North Manchester General Hospital had an opportunity
      last month to test their emergency skills at accident scenes, thanks to a
      training exercise with local firefighters. The exercise involved a mock-up of a
      road traffic accident, in which nurses experienced for example working outside in
      the cold and the noise of cutting equipment. Pictured in orange are A&E staff
      nurses Kelly Burns (left) and Ashley Thomson.

PMID- 27715181
TI  - ?
AB  - Rough justice? Magistrates have come under fire for awarding A&E sister Clare
      Walker only L75 in compensation after she was assaulted by a drunken patient. Ms
      Walker, who works at East Cheshire NHS Trust, is said to have experienced
      whiplash, sustained injuries to her wrist, knee and face, and suffered shock. She
      told the Macclesfield Express: 'The punishment hardly fits the crime. The message
      being sent out is that you can just go out and wallop a nurse and it will cost
      you less than 100 quid'.

PMID- 27715182
TI  - Flying to the rescue.
AB  - he Falkland Islands are probably best known for their unspoilt countryside,
      abundant wildlife, and the war between Argentina and the UK in 1982.

PMID- 27715183
TI  - Standing your ground.
AB  - As a senior emergency department staff nurse, I frequently work in our hospital's
      resuscitation area.

PMID- 27715184
TI  - Myocardial infarction.
AB  - Most studies that examine pre-hospital management of ST elevation myocardial
      infarction (STEMI) have involved either the accompanying of ambulance crews by
      physicians or the transmission of electrocardiograms (ECGs) to physicians at
      receiving hospitals.

PMID- 27715185
TI  - Chest pain services.
AB  - Ever since a survey in 2001 showed substantial variation in services for, and
      management of, acute, undifferentiated chest pain, the Department of Health has
      encouraged the development of chest pain units (CPUs) so that patients presenting
      with this condition receive better care.

PMID- 27715187
TI  - X-ray guidance to be reviewed after ENs raise concerns.
AB  - Emergency nurse leaders are to meet the RCN next month to discuss guidance on
      requesting X-ray and other images.

PMID- 27715189
TI  - Sugar Industry Science and Heart Disease.

PMID- 27715190
TI  - Board's eye view.
AB  - LAST AUGUST, Joe Strummer would have passed his 60th birthday. For those of you
      not as old or lucky as me, Joe was lead singer of The Clash, a UK punk band whose
      album, London Calling, was declared by Rolling Stone magazine to be the best
      album of the 1980s.

PMID- 27715191
TI  - Domestic Violence: The Essential Guide Greta McGough Domestic Violence: The
      Essential Guide Need2Know L9.99 106pp 9781861442239 1861442238 [Formula: see
      text].
AB  - THIS BOOK is part of the essential guide series from Need2Know and is an
      excellent starting point for exploring domestic violence.

PMID- 27715192
TI  - Design Features to Assist Patients with Dementia in General Hospitals and
      Emergency Departments Mary Marshall Design Features to Assist Patients with
      Dementia in General Hospitals and Emergency Departments University of Stirling
      L15 28pp 9781908063045 [Formula: see text].
AB  - ONE OF a series published by the Dementia Services Development Centre to assist
      professionals involved in the design ofbuildings used by people with dementia,
      thisbook covers topics such as the importance of design, why patients experience
      difficulties in some environments and not others, and the use of outside space.
      Best practice is illustrated with photographs and useful tips that can be
      implemented at little or no cost.

PMID- 27715194
TI  - Notice board.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27715193
TI  - Paediatric Advanced Life Support: A Practical Guide for Nurses Phil Jevon
      Paediatric Advanced Life Support: A Practical Guide for Nurses Wiley-Blackwell
      L25.99 264pp 9781405197762 1405197765 [Formula: see text].
AB  - MANY PRACTITIONERS have long sought an easily digestible and portable text
      focusing on paediatric emergency situations and the care provision required, and
      this book fits the bill.

PMID- 27715195
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27715196
TI  - Pre-hospital head injury.
AB  - Standards of pre-hospital care of traumatically injured patients often depend on
      the trauma systems being used.

PMID- 27715197
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27715198
TI  - Misuse of alcohol.
AB  - Alcohol may be a factor in up to 640,000 hospital admissions and nearly two
      million visits to emergency departments (EDs) in England and Wales each year,
      according to a study of attendance for emergency care at a hospital in south west
      England.

PMID- 27715199
TI  - Prognostic indicators in sepsis.
AB  - This prospective cohort study investigates the correlation between muscle tissue
      oxygen saturation (StO2) readings in emergency departments (EDs) and mortality
      rates at day 30 among patients who presented with severe sepsis (n=49).

PMID- 27715200
TI  - Mechanical chest compressions.
AB  - The authors of this study state that there is a lack of evidence about the
      efficiency of mechanical devices in producing chest compressions as an adjunct to
      resuscitation during cardiorespiratory arrest.

PMID- 27715201
TI  - Epidemiology of Injury in Olympic Sports Dennis J Caine Epidemiology of Injury in
      Olympic Sports et al International Olympic Committee and Wiley-Blackwell L108
      518pp 9781405173643 1405173645 [Formula: see text].
AB  - THIS EXCELLENT, up-to-date review of injuries in Olympic sports covers types,
      times and locations of injury, as well as specific contributory conditions. It
      covers every summer and winter Olympic sport, and pays particular attention to
      Paralympic events.

PMID- 27715202
TI  - If the tricorn hat fits.
AB  - READERS MAY know that this year marks Emergency Nurse's 20th year of publication.
      They are unlikely to know that it also marks my 20th year as a qualified nurse.

PMID- 27715203
TI  - Initial Management of Acute Medical PatientsSecond edition Initial Management of
      Acute Medical Patients Ian Wood and Michelle Garner Wiley-Blackwell L29.99 320pp
      9781444337167 1444337165 [Formula: see text].
AB  - ALTHOUGH THIS book is not intended for readers who want detailed descriptions of
      the treatment of acutely ill patients, it presents a useful overview of the
      subject.

PMID- 27715205
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27715208
TI  - Author's response.
AB  - As I explain in the book, I did not have enough room to cover every aspect of
      domestic violence in the detail it requires.

PMID- 27715206
TI  - The future of melanoma therapy: developing new drugs and improving the use of old
      ones.

PMID- 27715209
TI  - Victims of violence.
AB  - I HAVE just read Pat McCollum's review of the book, Domestic Violence: The
      Essential Guide by Greta McGough, which appears in October's Emergency Nurse.

PMID- 27715210
TI  - Board's eye view.
AB  - IN MARCH, the hospital in which I work, Queen Elizabeth Hospital Birmingham
      (QEHB), was designated a major trauma centre and is equipped to treat some of the
      most seriously injured patients in the West Midlands.

PMID- 27715212
TI  - Minor injury services.
AB  - Designating areas of emergency departments for the management of minor injuries
      can improve patients' experience, and increase emergency nurses' autonomy, skills
      and knowledge, according to a project report on the Foundation for Nursing
      Studies website at, http://tinyurl.com/c8sxhaa.

PMID- 27715211
TI  - Asthma practice guide.
AB  - To help improve asthma care, Primary Care Commissioning (PCC) has launched a
      practice guide for professionals, including emergency care staff, involved in
      care of people with asthma. It explains the case for improving outcomes for
      people with asthma and presents case studies to describe what good services
      should be like. One section looks specifically at the emergency management of
      acute episodes and makes several recommendations.

PMID- 27715213
TI  - Information on violence.
AB  - Guidance on how to encourage emergency care staff to collect and share
      information on violence without breaching standards of patient confidentiality
      has been published by the Department of Health.

PMID- 27715215
TI  - Competence update.
AB  - An RCN update of its competencies for adult and children's orthopaedic and trauma
      practitioners, including healthcare assistants and assistant or associate
      practitioners, is available on the college's website, at
      http://tinyurl.com/c66zkg7.

PMID- 27715214
TI  - Ambulatory care.
AB  - Ambulatory emergency care (AEC) can reduce pressure on the NHS by ensuring that
      emergency care takes place on the day of presentation and that admissions are
      avoided, says the Department of Health.

PMID- 27715216
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27715217
TI  - Health and safety.
AB  - The Health and Safety Executive's (HSE) cost-recovery scheme, Fee for
      Intervention, explains how organisations that break health and safety laws are
      liable for recovery of the HSE's costs, including those for inspections and
      taking enforcement actions. Organisations that comply with their legal
      obligations pay nothing.

PMID- 27715218
TI  - Patients who use drugs.
AB  - Online resources for drug treatment and recovery have been added to the National
      Treatment Agency for Substance Misuse (NTA) website, at www.nta.nhs.uk/recovery
      resources.aspx.

PMID- 27715219
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27715220
TI  - Educational poster.
AB  - In an attempt to reduce haemolysation rates in an Australian ED, Corkill ( 2012 )
      placed educational posters in staff toilet cubicles. This novel approach produced
      a statistically significant reduction in median haemolysis rates, from 4.92 per
      cent to 3.95 per cent (P=0.001), over a 12-month period.

PMID- 27715221
TI  - Therapeutic hypothermia.
AB  - There is growing evidence to support the use of mild therapeutic hypothermia
      (MTH), also known as targeted temperature management, in out-of-hospital patients
      who have experienced cardiac arrest. Reducing core body temperatures to 32-34
      degrees C can reduce mortality and neurological disability significantly among
      such patients, but recent surveys have shown that use of MTH is variable and
      there can be a considerable delay in initiating it.

PMID- 27715222
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27715223
TI  - War surgery field manual Swee Chai Ang War surgery field manual Erik Fosse Hans
      Husum Third World Network and Trauma Care Foundation L90 880pp 9788932729211
      [Formula: see text].
AB  - THIS IS a comprehensive field manual for medical personnel, in the UK or abroad,
      but especially those travelling to developing countries without access to other
      references.

PMID- 27715224
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27715225
TI  - Reducing waiting times.
AB  - WITH REFERENCE to the article 'The struggle to control waiting times', on page 8
      of April's Emergency Nurse, waits at emergency departments (EDs) could be reduced
      if patients who attend them had more information about local minor injuries units
      (MIUs).

PMID- 27715226
TI  - Return of homeless patients.
AB  - Many patients return to EDs within 28 days of discharge. If staff can recognise
      the patients who are more likely to re-present, they can offer interventions that
      reduce the likelihood of them doing so.

PMID- 27715227
TI  - Care for the bereaved.
AB  - WITNESSING SUDDEN death and managing bereavement are among the most difficult
      experiences emergency nurses can have.

PMID- 27715229
TI  - (Re)Thinking violence in health care settings Dave Holmes Trudy Rudge Amelie
      Perron (Re)Thinking violence in health care settings Ashgate L65 366pp
      9781409432661 1409432661 [Formula: see text].
AB  - THERE HAS been much discussion over the years about violence in healthcare
      settings and this book offers a refreshing approach to this persistent problem.
      It covers violence among healthcare providers, violence by patients towards
      healthcare staff, and institutional and managerial violence against healthcare
      workers and patients.

PMID- 27715228
TI  - Predicting neurological outcome.
AB  - To help identify patients who can benefit from MTH after out-of-hospital cardiac
      arrest, Okada et al ( 2012 ) have developed a prediction protocol. They performed
      a retrospective observational study of comatose patients who had been treated
      with MTH after out-of-hospital cardiac arrest, between January 2006 and February
      2011, in an eight-bed intensive care unit in Tokyo, Japan.

PMID- 27715230
TI  - Hope for the future.
AB  - AS 2012 draws to an end, emergency nurses across the UK are trying to cope with
      patients who have higher clinical acuity, as well as with increasing trolley
      waits and reductions in staff numbers.

PMID- 27715231
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27715235
TI  - Knee injuries.
AB  - Management and treatment of patella instability and fractures depend on several
      factors, including appropriate assessments, limb alignment, and the integrity of
      surrounding soft tissues and musculature.

PMID- 27715232
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27715237
TI  - Poisonous substances.
AB  - Management plans for children with ingestion problems who present to emergency
      departments often include toxicology screening tests to detect the presence of
      poisonous substances.

PMID- 27715236
TI  - Cardiopulmonary resuscitation.
AB  - Out-of-hospital cardiac arrest (OHCA) is a major public health problem around the
      world, despite recent increases in medical knowledge and improvements to patient
      survival rates.

PMID- 27715239
TI  - Go ahead for 'clot busting' drug for patients with stroke.
AB  - The National Institute for Health and Clinical Excellence (NICE) issued guidance
      last month on the use of the 'clot busting' drug, alteplase, for the treatment of
      acute ischaemic stroke.

PMID- 27715240
TI  - Human bite injury.
AB  - Human bite injuries are common presentations in EDs across the world and, in many
      such cases, plastic surgery is required.

PMID- 27715241
TI  - MoD drive to recruit nurses.
AB  - The Ministry of Defence (MoD) has increased the value of its 'golden hellos' for
      emergency and other specialist nurses, from L8,000 to L20,000.

PMID- 27715242
TI  - Guidance on voluntary work overseas.
AB  - Guidance has been launched to help nurses who want to use their skills to work
      with humanitarian organisations overseas.

PMID- 27715243
TI  - Call to train ENs on domestic abuse.
AB  - The RCN has backed calls for emergency care staff to receive more training to
      help them identify and assist patients who have experience of domestic abuse.

PMID- 27715244
TI  - ECA committee election announced.
AB  - The RCN has announced details of the forthcoming election to decide the new
      steering committee members of its Emergency Care Association (ECA).

PMID- 27715245
TI  - Violence against nurses.
AB  - As a result of spending almost 300 hours observing patients in an Australian
      emergency department (ED), researchers have devised a method for identifying
      patients or relatives who can become violent.

PMID- 27715246
TI  - ?
AB  - Award winning: A&E staff nurse Linsey Sheerin is among the four nurses who last
      month received commendations as part of the RCN Northern Ireland Nurse of the
      Year awards 2007. Ms Sheering, who works at the Mater Hospital, Belfast, was
      commended for her involvement in a project to enhance the knowledge and skills of
      A&E nursing staff in assessing and providing care to people with learning
      disabilities.

PMID- 27715248
TI  - Change matters.
AB  - Emergency care services have undergone enormous change over the past ten years,
      most of it associated with the four-hour emergency access target.

PMID- 27715249
TI  - Board's eye view.
AB  - What is it with emergency nurses and Both have the same goal, namely the hospital
      management teams? delivery of safe care within a period of four hours, yet they
      want to reach it in different ways.

PMID- 27715250
TI  - Clarification.
AB  - The article on paracetamol in the June issue of Emergency Nurse refers in Box 1
      to dosages.

PMID- 27715251
TI  - Jewellery protocols.
AB  - The control of hospital acquired infection is an important issue in all areas of
      practice, including emergency care, and NHS trusts are expected to enforce
      guidelines on this issue.

PMID- 27715252
TI  - In response....
AB  - The definition of suicidal behaviour used in the study referred to above was
      taken from the Australian Commonwealth Department of Health and Aged Care, now
      the Australian Government Department of Health and Ageing.

PMID- 27715253
TI  - An Overview of Analytical Methods for the Determination of Monoamine Oxidase
      Inhibitors in Pharmaceutical Formulations and Biological Fluids.
AB  - Monoamine oxidase inhibitors (MAOIs) were the first type of antidepressant
      developed. MAOIs elevate the levels of norepinephrine, serotonin, and dopamine by
      inhibiting an enzyme called monoamine oxidase. They are also used in the
      treatment of Parkinson's disease, tuberculosis, and several other disorders.
      Therefore, it is very important to develop efficient analytical methods for
      monitoring and management. There are two isoforms of monoamine oxidase, MAO-A and
      MAO-B. In this article, analyses of MAOIs in pharmaceutical formulations and
      biological fluids were reviewed from 2000 to the present, including all types of
      chromatographic, spectrophotometric, electrophoretic, and voltammetric
      techniques, focusing on isoniazid, tranylcypromine, moclobemide, rasagiline, and
      selegiline.

PMID- 27715254
TI  - The Angiotensin-(1-7)/Mas Axis Improves Pancreatic beta-Cell Function in Vitro
      and in Vivo.
AB  - The angiotensin-converting enzyme 2/angiotensin (Ang)-(1-7)/Mas axis of the renin
      angiotensin system often opposes the detrimental effects of the angiotensin
      converting enzyme/Ang II/Ang II type 1 receptor axis and has been associated with
      beneficial effects on glucose homeostasis, whereas underlying mechanisms are
      mostly unknown. Here we investigate the effects of Ang-(1-7) and its receptor Mas
      on beta-cell function. Isolated islets from Mas-deficient and wild-type mice were
      stimulated with Ang-(1-7) or its antagonists and effects on insulin secretion
      determined. Islets' cytoplasmic calcium and cAMP concentrations, mRNA amounts of
      Ins1, Ins2, Pdx1, and Mafa and effects of inhibitors of cAMP downstream signaling
      were determined. Ang-(1-7) was also applied to mice by osmotic pumps for 14 days
      and effects on glucose tolerance and insulin secretion were assessed. Ang-(1-7)
      increased insulin secretion from wild-type islets, whereas antagonists and
      genetic Mas deficiency led to reduced insulin secretion. The Mas-dependent
      effects of Ang-(1-7) on insulin secretion did not result from changes in insulin
      gene expression or changes in the excitation-secretion coupling but from
      increased intracellular cAMP involving exchange protein activated directly by
      cAMP. Administration of Ang-(1-7) in vivo had only marginal effects on glucose
      tolerance in wild-type mice but still resulted in improved insulin secretion from
      islets isolated of these mice. Interestingly, although less pronounced than in
      wild types, Ang-(1-7) still affected insulin secretion in Mas-deficient islets.
      The data indicate a significant function of Ang-(1-7) in the regulation of
      insulin secretion from mouse islets in vitro and in vivo, mainly, but not
      exclusively, by Mas-dependent signaling, modulating the accessory pathway of
      insulin secretion via increase in cAMP.

PMID- 27715255
TI  - Pulse and Surge Profiles of Luteinizing Hormone Secretion in the Mouse.
AB  - Using a new tail-tip bleeding procedure and a sensitive ELISA, we describe here
      the patterns of LH secretion throughout the mouse estrous cycle; in
      ovariectomized mice; in ovariectomized, estradiol-treated mice that model
      estrogen-negative and -positive feedback; and in transgenic GNR23 mice that
      exhibit allele-dependent reductions in GnRH neuron number. Pulsatile LH secretion
      was evident at all stages of the estrous cycle, with LH pulse frequency being
      approximately one pulse per hour in metestrous, diestrous, and proestrous mice
      but much less frequent at estrus (less than one pulse per 4 h). Ovariectomy
      resulted in substantial increases in basal and pulsatile LH secretion with pulses
      occurring approximately every 21 minutes. Chronic treatment with negative
      feedback, estradiol-filled capsules returned LH pulse frequency to intact
      follicular phase levels, although pulse amplitude remained elevated. On the
      afternoon of proestrus, the LH surge was found to begin in a highly variable
      manner over a 4-hour range, lasting for more than 3 hours. In contrast,
      ovariectomized, estradiol-treated, positive-feedback mice exhibited a relatively
      uniform surge onset at approximately 0.5 hour prior to lights out. Gonadectomized
      wild-type and heterozygous GNR23 (~200 GnRH neurons) male mice exhibited an LH
      pulse every 60 minutes. Homozygous GNR23 mice (~80 GnRH neurons) had very low
      basal LH concentrations but continued to exhibit small amplitude LH pulses every
      90 minutes. These studies provide the first characterization in mice of pulse and
      surge modes of LH secretion across the estrous cycle and demonstrate that very
      few GnRH neurons are required for pulsatile LH secretion.

PMID- 27715256
TI  - Recommendations to support informal carers of people living with motor neurone
      disease.
AB  - Informal carers are increasingly providing specialist care at home for people
      living with motor neurone disease. The carers may experience significant
      deterioration in their quality of life as a result of the physical and
      psychological burden they undertake. This systematic review seeks to provide
      evidence-based recommendations to enable healthcare professionals to support
      carers appropriately to maintain their wellbeing and to continue providing care
      at home. Inclusion criteria included articles focusing on the experience of
      informal carers of people with motor neurone disease, particularly when reporting
      on their perspective of professional services. Twenty-three studies were included
      and a thematic analysis was undertaken. Four key recommendations were identified:
      providing support, early access to palliative care, information regarding
      availability of services, and offering carers training for using specialist
      equipment. These recommendations offer healthcare professionals practical, cost
      effective suggestions to improve existing services.

PMID- 27715257
TI  - A multiple case study of patient journeys in Wales from A&E to a hospital ward or
      home.
AB  - The health service is having to plan for an increasingly older population putting
      extra demand on services, with a greater emphasis on providing care at home. A
      health board in Wales brought in an Early Response Service, which assessed
      whether patients attending accident and emergency needed to be admitted to
      hospital or could receive care at home. This qualitative study looked at the
      experiences of both patients and staff members in both settings. A multiple case
      study was undertaken using semi-structured interviews. The theoretical framework
      was derived from Kolcaba's comfort theory and the bio-psycho-social model. Staff
      were identifying the most suitable patients for care at home and all hospital
      admissions were necessary, as the patients required greater medical/surgical
      intervention than those cared for at home.

PMID- 27715258
TI  - The value of mindfulness in people with long-term conditions.

PMID- 27715259
TI  - Not what the doctor ordered.

PMID- 27715260
TI  - Is there a role for probiotics in older people?

PMID- 27715261
TI  - Nurturing ethical leadership.

PMID- 27715262
TI  - District nurses must do more to comply with health care sharps regulations.
AB  - The Health and Safety Executive have completed an inspection initiative focussing
      on the prevention and management of sharps injuries in forty NHS organisations.
      Health and safety breaches were found in 90% of the services visited and
      inspectors issued improvement notices to 45% of those NHS organisations. In this
      article Richard Griffith sets out the key findings of the inspection initiative
      and considers their impact on district nursing practice.

PMID- 27715263
TI  - Managing long-term conditions in primary and community care.
AB  - Health care policy in the UK continues to focus on provision of care in the
      community. For people with long-term conditions it has long been accepted that
      care should be predominantly in the primary and community care setting, with a
      focus on case management for those with complex needs. Community nurses are
      ideally placed to provide care to all people with long-term conditions, from
      health promotion, prevention and encouraging self-care to caring for people with
      more complex needs, comorbidities and end-of-life care. Community nurses are an
      essential element of the multidisciplinary team and should take the lead in
      delivering complex care at home to people with long-term conditions, while
      maintaining a focus on developing self-care, empowerment, community engagement
      and acting as an advocate for clients and their carers.

PMID- 27715264
TI  - Matters of life and death: the new Government report on choice in end-of-life
      care.

PMID- 27715265
TI  - Urinary catheterisation in the community: Exploring challenges and solutions.

PMID- 27715266
TI  - Demystifying cancer care in the community.

PMID- 27715267
TI  - How do we achieve a good death?

PMID- 27715269
TI  - A new emergency care nursing role.
AB  - The rise in attendance at emergency departments (EDs), coupled with the
      responsibility of the health service to meet the needs of an increasingly diverse
      range of patients, has made healthcare delivery increasingly complex and
      specialised.

PMID- 27715268
TI  - Demand on district nursing services leaving staff 'on their knees,' says King's
      Fund.

PMID- 27715270
TI  - Non-invasive ventilation.
AB  - This is a study of the use of non-invasive ventilation (NIV) in UK emergency
      departments (EDs).

PMID- 27715271
TI  - Emergency care of the patient with a heart attack R Gamon , T Quinn , B Parr
      Emergency care of the patient with a heart attack Churchill Livingstone L16.99
      044310249 X 044310249 X [Formula: see text].
AB  - Attendance at emergency departments (EDs) of patients with cardiac chest pain is
      becoming increasingly common and, as with anything that has become 'the norm', we
      may think that there is little more to learn about this phenomenon.

PMID- 27715272
TI  - Paediatric care.
AB  - The authors of this study wanted to investigate whether, and to what extent, the
      treatment of paediatric emergency patientsis based on evidence, The authors of
      this study wanted to investigate especially as clinicians are increasingly being
      called on to justify their treatment decisions with valid, up-to-date evidence.

PMID- 27715273
TI  - Community based cardiac care.
AB  - It is acknowledged that coronary heart disease is the most common cause of death,
      and the single main cause of premature death, for both men and women in the UK.

PMID- 27715274
TI  - Treating headaches.
AB  - The objective of this north American study is to evaluate whether or not the
      addition of intra-venous dexamethasone to standard emergency to standard
      emergency department (ED) therapy for benign head-ache reduces the incidence of
      headache reoccurrence at between 48 and 72 hours.

PMID- 27715275
TI  - The secrets of success.
AB  - The national emergency care practitioner (ECP) initiative began in response to a
      project at Coventry and Warwickshire Partnership NHS Trust to develop paramedic
      and nursing skills, and was informed by guidance published by the Department of
      Health last year in its review of ambulance services, Taking Health Care to the
      Patient.

PMID- 27715276
TI  - A chest pain is your body saying call 999.
AB  - Heartfelt message:40 per cent of people would not make 999 their first call if
      they suspected they were having a heart attack, a survey for the British Heart
      Foundation (BHF) has revealed. And an even greater number, 64 per cent, say they
      would call someone other than the emergency services first if they were
      experiencing chest pain. The findings of the poll were revealed as the BHF last
      month launched its Doubt Kills campaign, urging people not to delay calling 999
      if they experience chest pain.

PMID- 27715277
TI  - Conference call.
AB  - > Emergency nurses have been invited to attend a conference on improving patient
      experience in emergency care and redesigning roles and ways of working in A&E.
      The conference is being held on January 9 at Manchester Conference Centre.

PMID- 27715278
TI  - ECA members discuss industrial action to protest against staff cutsbacks.
AB  - The RCN Emergency Care Association (ECA) is to issue members with information on
      taking industrial action amid concerns that staffing cutbacks are putting patient
      lives in danger.

PMID- 27715279
TI  - Manifesto call.
AB  - RCN Wales has put improving access to emergency care at the top of its demands in
      the run up to Welsh Assembly Government elections next May.

PMID- 27715280
TI  - Your letter.
AB  - In January 2000, BBC One's Panorama presented a damning view of the paramedic
      profession, and the shortfalls in its training and education methods.

PMID- 27715281
TI  - ?
AB  - Blood test:emergency nurses and other clinical staff who are involved in blood
      transfusions should have their competencies assessed formally every three years,
      according to the National Patient Safety Agency. The advice last month to all NHS
      organisations also urges the risk assessment of local transfusion procedures and
      using barcodes or other electronic identification systems to track blood. The
      safer practice notice and associated blood safety resources are available at
      www.npsa.nhs.uk/health/alerts/.

PMID- 27715282
TI  - Fines for abuse.
AB  - Patients who abuse A&E staff at Royal Bolton Hospital can now be fined L80 under
      a three-month pilot scheme being run this winter.

PMID- 27715284
TI  - Let's get it right.
AB  - Shadow health secretary Andrew Lansley may have his own, political, reasons for
      whipping up a storm about emergency services being under threat of closure but,
      judging by the views expressed to me by many attendees at the RCN Emergency Care
      Association (ECA) annual conference, emergency department (ED) staff do feel
      threatened.

PMID- 27715285
TI  - New RCN chair.
AB  - Kevin Randall (pictured) has been elected chair of the RCN Emergency Care
      Association.

PMID- 27715287
TI  - Cardboard Commentary: A Qualitative Analysis of the Signs From America's Streets.

PMID- 27715286
TI  - Risk factors for being the at-fault driver: A case-control study.
AB  - OBJECTIVE: It is estimated that road traffic accidents are globally responsible
      for approximately 1.2 million deaths and 20 to 50 million injuries. About 70% of
      traffic incidences (TIs) occur in developing countries and among countries with
      high TI rates; Iran is the first. The aim of this study was to measure the
      association between being responsible for a traffic accident and some vehicle,
      human; and environmental related factors in Yasuj, a city with a high incidence
      of road traffic injuries and deaths in Iran. METHODS: This is a time-, date-, and
      place-matched case-control study conducted in 2015 using all traffic accidents
      registered and investigated by police during 2012. In total, 194 drivers were
      considered the at-fault driver in a traffic accident and the 194 drivers in the
      same collisions were included in the analysis. RESULTS: Based on the results from
      multivariate conditional logistic regression, significant associations between
      vehicle maneuver (ORTurn to right or left/Moving forward = 11.10, 95% confidence
      interval [CI], 1.77-69.58, P = .01) and age (odds ratio [OR] = 1.11, 95% CI,
      1.004-1.22, P = .04) and the chance of being an at-fault driver were found.
      CONCLUSION: Driver behavior-related interventions including training and law
      enforcement seem to be more effective in reducing road traffic accidents in Iran.

PMID- 27715289
TI  - World Health Organization Reform-A Normative or an Operational Organization?

PMID- 27715290
TI  - Finance and Governance: Critical Challenges for the Next WHO Director-General.

PMID- 27715291
TI  - A New Leader for a New World Health.

PMID- 27715293
TI  - The Election of the Next World Health Organization Director-General Explained to
      a Visitor From Mars.

PMID- 27715294
TI  - Building Inclusion: Toward an Aging- and Disability-Friendly City.

PMID- 27715295
TI  - Hospitals Should Help Communities Prepare for Climate Change.

PMID- 27715296
TI  - Should We Continue to Perform Pap Smears on Women Who No Longer Have a Cervix?

PMID- 27715297
TI  - The South Carolina Comprehensive Health Education Act Needs to Be Amended.

PMID- 27715298
TI  - DA Henderson, Smallpox Eradicator.

PMID- 27715299
TI  - A Public Health of Consequence: Review of the November 2016 Issue of AJPH.

PMID- 27715301
TI  - The Cuban Experience in the Elimination of Mother-to-Child Transmission of
      Congenital Syphilis.

PMID- 27715303
TI  - At the Roots of The World Health Organization's Challenges: Politics and
      Regionalization.
AB  - The World Health Organization's (WHO's) leadership challenges can be traced to
      its first decades of existence. Central to its governance and practice is
      regionalization: the division of its member countries into regions, each
      representing 1 geographical or cultural area. The particular composition of each
      region has varied over time-reflecting political divisions and especially
      decolonization. Currently, the 194 member countries belong to 6 regions: the
      Americas (35 countries), Europe (53 countries), the Eastern Mediterranean (21
      countries), South-East Asia (11 countries), the Western Pacific (27 countries),
      and Africa (47 countries). The regions have considerable autonomy with their own
      leadership, budget, and priorities. This regional organization has been
      controversial since its beginnings in the first days of WHO, when representatives
      of the European countries believed that each country should have a direct
      relationship with the headquarters in Geneva, Switzerland, whereas others
      (especially the United States) argued in favor of the regionalization plan. Over
      time, regional directors have inevitably challenged the WHO directors-general
      over their degree of autonomy, responsibilities and duties, budgets, and national
      composition; similar tensions have occurred within regions. This article traces
      the historical roots of these challenges.

PMID- 27715304
TI  - Whither WHO? Our Global Health Leadership.

PMID- 27715305
TI  - Lock-In Programs and the Opioid Epidemic: A Call for Evidence.

PMID- 27715306
TI  - Correlates of Sugar-Sweetened Beverages Purchased for Children at Fast-Food
      Restaurants.
AB  - OBJECTIVES: To determine consumer and fast-food purchase characteristics
      associated with the purchase of a sugar-sweetened beverage, as well as calories
      and grams of sugar, for children at a fast-food restaurant. METHODS: We completed
      cross-sectional analyses of fast-food restaurant receipts and point-of-purchase
      surveys (n = 483) collected during 2013 and 2014 in New York City and Newark and
      Jersey City, New Jersey. RESULTS: Caregivers purchased beverages for half of all
      children in our sample. Approximately 60% of these beverages were sugar-sweetened
      beverages. Fast-food meals with sugar-sweetened beverages had, on average, 179
      more calories than meals with non-sugar-sweetened beverages. Being an adolescent
      or male, having a caregiver with a high school degree or less, having a caregiver
      who saw the posted calorie information, ordering a combination meal, and eating
      the meal in the restaurant were associated with ordering a sugar-sweetened
      beverage. Purchases that included a combination meal or were consumed in the
      restaurant included more beverage grams of sugar and calories. CONCLUSIONS:
      Characteristics of fast-food purchases appear to have the largest and most
      important association to beverage calories for children at fast-food restaurants.
      Targeting fast-food restaurants, particularly combination meals, may improve
      childhood obesity rates.

PMID- 27715309
TI  - AJPH Global News.

PMID- 27715308
TI  - World Health Organization: Overhaul or Dismantle?

PMID- 27715307
TI  - Challenges and Innovations in Surveying the Governmental Public Health Workforce.
AB  - Surveying governmental public health practitioners is a critical means of
      collecting data about public health organizations, their staff, and their
      partners. A greater focus on evidence-based practices, practice-based systems
      research, and evaluation has resulted in practitioners consistently receiving
      requests to participate in myriad surveys. This can result in a substantial
      survey burden for practitioners and declining response rates for researchers.
      This is potentially damaging to practitioners and researchers as well as the
      field of public health more broadly. We have examined recent developments in
      survey research, especially issues highly relevant for public health practice. We
      have also proposed a process by which researchers can engage with practitioners
      and practitioner groups on research questions of mutual interest.

PMID- 27715312
TI  - How motorcycle helmets affect trauma mortality: Clinical and policy implications.
AB  - BACKGROUND: Motorcycles are the most popular vehicles in Taiwan, where more than
      14.8 million motorcycles (1 motorcycle per 1.6 people) are in service. Despite
      the mandatory helmet law passed in 1997, less than 80% of motorcyclists in Taiwan
      wear helmets. OBJECTIVE: The objective of this study was to analyze the effect of
      using motorcycle helmets on fatality rates. METHODS: A clinical data set
      including 2,868 trauma patients was analyzed; the cross-sectional registration
      database was administered by a university medical center in Central Taiwan. A
      path analysis framework and multiple logistic regressions were used to estimate
      the marginal effect of helmet use on mortality. RESULTS: Using a helmet did not
      directly reduce the mortality rate but rather indirectly reduced the mortality
      rate through intervening variables such as the severity of head injuries, number
      of craniotomies, and complications during therapeutic processes. Wearing a helmet
      can reduce the fatality rate by 1.3%, the rate of severe head injury by 34.5%,
      the craniotomy rate by 7.8%, and the rate of complications during therapeutic
      processes by 1.5%. These rates comprise 33.3% of the mortality rate for people
      who do not wear helmets, 67.3% of the severe head injury rate, 60.0% of the
      craniotomy rate, and 12.2% of the rate of complications during therapeutic
      processes. DISCUSSION: Wearing a helmet and trauma system designation are crucial
      factors that reduce the fatality rate.

PMID- 27715313
TI  - No Dog Left Behind: A Hedonic Pricing Model for Animal Shelters.
AB  - Companion animal overpopulation is a growing problem in the United States. In
      addition to strays, an average of 324,500 nonhuman animals are relinquished to
      shelters yearly by their caregivers due to family disruption (divorce, death),
      foreclosure, economic problems, or minor behavioral issues. As a result,
      estimates of animals in shelters range from 3 million to 8 million, and due to
      overcrowding, euthanasia is common. This analysis seeks to determine the
      appropriate pricing mechanisms to clear animal shelters of dogs in the manner
      most desirable-that is, through adoption. Based on a survey of Michigan
      residents, it is clear there are a number of correlations between the traits of
      dogs and the individuals who care for them. Hedonic pricing models indicate that
      animal shelters need to proactively vary their pricing systems to discount
      particular traits, specifically for mixed-breed, older, and black dogs. Premiums
      can be charged for puppies, purebred dogs, and those who have received specific
      services such as microchipping.

PMID- 27715314
TI  - Using MMPI-2-RF Correlates to Elucidate the PCL-R and Its Four Facets in a Sample
      of Male Forensic Psychiatric Patients.
AB  - This study documents the associations between the MMPI-2-RF (Ben-Porath &
      Tellegen, 2008 ) scale scores and the Psychopathy Checklist Revised (PCL-R; Hare,
      2003 ) facet scores in a forensic psychiatric sample. Objectives were to
      determine how the MMPI-2-RF scales might enhance substantive understanding of the
      nature of the 4 PCL-R facets and to discern possible implications for the
      treatment of psychopathic patients. A sample of 127 male forensic psychiatric
      offenders admitted to a Dutch forensic psychiatric hospital completed the PCL-R
      and the MMPI-2. Exploratory stepwise regression analyses assessed the prediction
      of the PCL-R total and its facet scores from MMPI-2-RF scales at its 3
      hierarchical levels. Conceptually meaningful results emerged at each level of the
      MMPI-2-RF hierarchy, including several consistent differences between predictor
      sets across the facets. Interestingly, ideas of persecution (RC6) was a specific
      predictor of PCL-R Facet 2, a facet noted for its association with treatment
      failure. Results are compared and contrasted to the extant body of empirical work
      to date, and some tentative clinical implications are offered.

PMID- 27715316
TI  - Using the Research Domain Criteria Framework to Explore Associations Between MMPI
      2-RF Constructs and Physiological Variables Assessed by Eye-Tracker Technology.
AB  - The National Institute of Mental Health has proposed a paradigm shift in the
      conceptualization of psychopathology, abandoning the traditional categorical
      model in favor of one based on hierarchically organized dimensional constructs
      (Insel et al., 2010 ). One explicit goal of this initiative, the Research Domain
      Criteria (RDoC) project, is to facilitate the incorporation of newly available
      neurobiologic variables into research on psychopathology. The Minnesota
      Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF; Ben-Porath &
      Tellegen, 2008/2011 ) represents a similar paradigm shift, also adopting a
      hierarchical arrangement of dimensional constructs. This study examined
      associations between MMPI-2-RF measures of psychopathology and eye-movement
      metrics. Participants were college students (n = 270) who completed the MMPI-2-RF
      and then viewed a sequence of 30-s video clips. Results show a pattern of
      positive correlations between pupil size and emotional/internalizing dysfunction
      scales when viewing video eliciting negative emotional reactions, reflecting
      greater arousability in individuals with higher scores on these measures. In
      contrast, when viewing stimuli depicting angry, threatening material, a clear
      pattern of negative correlations was found between pupil size and
      behavioral/externalizing trait measures. These data add to the construct validity
      of the MMPI-2-RF and support the use of the RDoC matrix as a framework for
      research on psychopathology.

PMID- 27715317
TI  - Treatment of substance use disorders in schizophrenia.
AB  - BACKGROUND: Substance use disorders (SUDs) represent a great barrier to
      functional recovery for individuals with schizophrenia. It is important to use
      research on treatment of SUDs in schizophrenia to guide treatment recommendations
      and program planning. OBJECTIVES: We review studies of pharmacological and
      psychosocial interventions to treat SUDs in individuals with schizophrenia.
      METHODS: The criteria used to select studies for inclusion are (1) the percentage
      of the sample with a schizophrenia spectrum diagnosis is at least 25%; (2)
      participants have a comorbid SUD or problem use of substances; (3) an
      intervention for SUD is provided; (4) a substance use-related outcome is
      measured; and (5) the study design enabled examination of pre-post outcome
      measures including open label trials, nonrandomized evaluations (quasi
      experimental designs, nonrandom assignment to groups), or randomized controlled
      trials. RESULTS: There are few psychopharmacology outcomes studies. Most have
      examined use of antipsychotic medications to treat SUDs in schizophrenia. Several
      trials have yielded positive findings for naltrexone in reducing drinking
      compared to placebo in this population. Motivational and cognitive-behavioral
      interventions are associated with decreased substance use in several trials.
      CONCLUSION: Treatment for SUDs is feasible within a range of settings and
      acceptable to many individuals with schizophrenia. All individuals with
      schizophrenia should be offered brief or more extended psychosocial interventions
      that incorporate discussion of personal reasons to change and training in
      cognitive-behavioral strategies to reduce use, cope with cravings and stress, and
      avoid relapse. Future research must include larger samples, longitudinal designs,
      and similar outcome measures across studies.

PMID- 27715315
TI  - Alzheimer's disease and chronic traumatic encephalopathy: Distinct but possibly
      overlapping disease entities.
AB  - BACKGROUND: Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE)
      have long been recognized as sharing some similar neuropathological features,
      mainly the presence of neurofibrilary tangles and hyperphosphorylated tau, but
      have generally been described as distinct entities. Evidence indicates that
      neurotrauma increases the risk of developing dementia and accelerates the
      progression of disease. Findings are emerging that CTE and AD may be present in
      the same patients. CLINICAL PRESENTATION: This study presents a series of
      previously unpublished cases, with one case demonstrating possible neurotrauma
      related AD, one pure CTE, and an example of a case exhibiting features of both AD
      and CTE. The future significance of this work lies not only in the confirmation
      of AD-CTE co-existence, but, more importantly, ways of generating a hypothesis
      about the possibility that CTE may accelerate AD development. Understanding the
      relationship between neurotrauma and neurodegenerative disease will help
      elucidate how distinct disease entities can co-exist in the same patient. It will
      ultimately require the use of pre-clinical animal models and repeat injury
      paradigms to investigate clinically relevant injury mechanisms. These models
      should produce a CTE-like phenotype that must be both neuropathologically and
      behaviourally similar to human disease. CONCLUSION: This case series and review
      of the literature presents a discussion of AD and CTE in the context of
      neurotrauma. It highlights recent work from repetitive neurotrauma models with an
      emphasis on those exhibiting a CTE-like phenotype. Potential mechanisms of
      interest shared amongst AD and CTE are briefly addressed and future experiments
      are advocated for to enhance understanding of CTE pathophysiology and the
      relationship between CTE and AD.

PMID- 27715318
TI  - Effect of anticipatory stress on placebo alcohol consumption in a bar laboratory.
AB  - BACKGROUND: Only one laboratory study has examined the relation between stress
      and alcohol use in an ecologically valid drinking context. In that prior study,
      drinking was measured after the stressful situation. OBJECTIVE: To examine the
      effect of an anticipatory stressor, and trait social anxiety on "alcohol"
      consumption in a bar laboratory. METHODS: College students aged 18 and older (N =
      127) in same-sex groups of two or three participants took part in a study that
      ostensibly examined alcohol's effect on language fluency. Using a between
      subjects design, participants were randomly assigned to a stress or control
      condition. Participants in the stress condition anticipated giving a stressful
      speech for the fluency procedure, whereas those in the control group anticipated
      a nonstressful activity. Before the alleged fluency task, groups could order and
      consume mixed drinks ad lib in a bar laboratory. No beverages actually contained
      alcohol, but we used a validated procedure to ensure that participants included
      in these analyses were deceived. Primary analyses were performed with a
      hierarchical linear model (HLM) due to a substantial group/modeling effect.
      RESULTS: Counter to expectations, participants in the control group consumed more
      placebo alcohol than those in the stress condition. This main effect was
      moderated by past 3 months' drinks per week, such that the effect was attenuated
      (or reversed) among heavy drinkers. No main or interaction effects were observed
      for trait social anxiety. CONCLUSIONS: Some stressors (i.e., those invoking
      performance anxiety) may decrease consumption. People with higher levels of
      alcohol involvement might be especially motivated to drink for tension reduction
      purposes.

PMID- 27715319
TI  - Preliminary evaluation of a measure for reliable assessment of need for constant
      visual observation in adults with traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To develop and provide initial validation of a measure for
      accurately determining the need for Constant Visual Observation (CVO) in patients
      with traumatic brain injury (TBI) admitted to inpatient rehabilitation. RESEARCH
      DESIGN: Rating scale development and evaluation through Rasch analysis and
      assessment of concurrent validity. METHODS AND PROCEDURES: One hundred and thirty
      four individuals with moderate-severe TBI were studied in seven inpatient brain
      rehabilitation units associated with the National Institute for Disability,
      Independent Living and Rehabilitation Research (NIDILRR) TBI Model System.
      Participants were rated on the preliminary version of the CVO Needs Assessment
      scale (CVONA) and, by independent raters, on the Levels of Risk (LoR) and
      Supervision Rating Scale (SRS) at four time points during inpatient
      rehabilitation: admission, Days 2-3, Days 5-6 and Days 8-9. OUTCOMES AND RESULTS:
      After pruning misfitting items, the CVONA showed satisfactory internal
      consistency (Person Reliability = 0.85-0.88) across time points. With reference
      to the LoR and SRS, low false negative rates (sensitivity > 90%) were associated
      with moderate-to-high false positive rates (29-56%). CONCLUSIONS: The CVONA may
      be a useful objective metric to complement clinical judgement regarding the need
      for CVO; however, further prospective study is desirable to further assess its
      utility in identifying at-risk patients, reducing adverse events and decreasing
      CVO costs.

PMID- 27715320
TI  - Association between chronotype and nonrestorative sleep in a college population.
AB  - Nonrestorative sleep (NRS), characterized by a lack of refreshment upon
      awakening, has received little attention in the sleep literature even though it
      can occur and cause impairment apart from other sleep difficulties associated
      with insomnia. The Restorative Sleep Questionnaire (RSQ) is one of the first
      validated self-report instruments for investigating NRS severity, presenting new
      opportunities to explore what factors predict and perhaps contribute to
      unrefreshing sleep. The present study sought to determine whether inherent
      circadian preference for morning or evening activity, known as chronotype,
      predicted restorative sleep in 164 college undergraduates who completed daily
      RSQs over 2 weeks. The participants who endorsed greater orientation to evening
      activity on the morningness-eveningness questionnaire reported significantly less
      average restorative sleep across their full sampling period, and this association
      was maintained after accounting for demographic factors, number of sleep-relevant
      psychiatric and medical diagnoses, sleep diary parameters, self-reported status
      as an insomniac and ratings of sleep quality. When analyses were conducted
      separately for weekday and weekend RSQ scores, eveningness predicted NRS
      independently of extraneous variables only during the workweek, not during
      Saturday and Sunday. These findings have implications for the developing
      conceptualization of NRS, and continue the work of elucidating the
      interconnections between common sleep disturbances and the circadian system.

PMID- 27715321
TI  - Changes in the diurnal rhythms of cortisol, melatonin, and testosterone after 2,
      4, and 7 consecutive night shifts in male police officers.
AB  - Night work is associated with a large range of acute health problems and possibly
      also health consequences in the long run. Yet, only very few field studies
      specifically investigate the effects of consecutive night shift on key
      physiological regulatory systems. In this field study, we investigated the
      effects of consecutive night shifts on three hormones, melatonin, cortisol, and
      testosterone, among police officers at work. More specifically, the aim was to
      investigate how the diurnal rhythms of melatonin, cortisol, and testosterone
      responded to two, four, and seven consecutive night shifts and a corresponding
      number of days for recovery. The study was part of the "In the Middle of the
      Night" project and included 73 male police officers from five different police
      districts. The participants were exposed to three intervention conditions: "2+2":
      two consecutive night shifts followed by two consecutive day recovery days;
      "4+4": four consecutive night shifts followed by four consecutive recovery days;
      "7+7": seven consecutive night shifts followed by seven consecutive recovery
      days. On the last day with night shift and the last recovery day in each
      intervention, the participants collected saliva samples every 4th hour when
      awake. The diurnal rhythms of melatonin, cortisol, and testosterone were all
      affected differently by an increasing number of consecutive night shifts: the
      amplitude of the melatonin rhythm was suppressed by 4.9% per day (95% CI 1.4-8.2%
      per day; p = 0.006). The diurnal rhythm of cortisol phase was delayed with an
      increasing number of night shifts by 33 min/day (95% CI 18-48 min per day; p <=
      0.001), but did not show any changes in amplitude. For the diurnal rhythm of
      testosterone, there was no effect of the number of consecutive night shifts and
      the diurnal rhythm completely followed the sleep/wake cycle. We found that there
      were no differences in the rhythms of melatonin, cortisol, and testosterone after
      2, 4, and 7 recovery days, respectively. In conclusion, we found signs of
      desynchronization in terms of suppressed amplitude of melatonin and phase delay
      of salivary cortisol as a consequence of the increasing number of consecutive
      night shifts among police officers at work. Lack of synchronization has been
      suggested as a possible mechanism linking night work to disease, but this remains
      to be determined.

PMID- 27715323
TI  - Answer to letter: Factors affecting melatonin secretion that may change melatonin
      pattern, by Yvan Touitou, Michael H. Smolensky and Alain Reinberg.

PMID- 27715322
TI  - Effects of an Exercise Intervention in Frail Older Patients with Chronic
      Obstructive Pulmonary Disease Hospitalized due to an Exacerbation: A Randomized
      Controlled Trial.
AB  - The objective of this study was to determine whether an exercise intervention
      using a pedal exerciser is able to reduce disability in frail older patients with
      chronic obstructive pulmonary disease (COPD) during hospitalization due to an
      acute exacerbation. This study was a randomized, single-blind clinical trial.
      Fifty-eight frail older patients admitted to hospital due to an acute
      exacerbation of COPD (AECOPD) were included in this study. All patients received
      standard medical and pharmacological care. Patients assigned to the intervention
      group also received an exercise intervention. The main outcome measures were
      balance, muscle strength, and exercise capacity. Significant between-group
      differences were found in muscle strength (p = 0.028) and balance (p = 0.013)
      after the intervention. All the variables improved significantly (p < 0.05) in
      the exercise intervention group. In the intervention group, the mean difference
      in muscle strength between baseline and discharge was 10.47 N. Balance also
      improved, showing a mean difference of 7.56 seconds on the right leg and 6.57
      seconds on the left leg. Exercise capacity improved as well, with a difference of
      4.97 stands between baseline and discharge. All the variables showed impairment
      in the control group. In conclusion, an exercise intervention using a pedal
      exerciser during the hospital stay of frail elderly patients with an AECOPD
      improves muscle strength, balance, and exercise capacity.

PMID- 27715324
TI  - Social jetlag affects subjective daytime sleepiness in school-aged children and
      adolescents: A study using the Japanese version of the Pediatric Daytime
      Sleepiness Scale (PDSS-J).
AB  - The aim of this study was to elucidate the level of daytime sleepiness in
      Japanese school-aged children and adolescents, and to examine associated factors
      including sleep loss and social jetlag using the Japanese version of the
      Pediatric Daytime Sleepiness Scale (PDSS-J). After the linguistic validation of
      the PDSS-J with a multi-step translation methodology, consisting of forward
      translation, back translation, expert review and cognitive debriefing interviews,
      we conducted a psychometric validation for 492 students aged 11-16 years (46.7%
      boys) of public elementary school, junior high school and high school, using the
      PDSS-J, the Karolinska Sleepiness Scale (KSS), and bedtimes and wake-up times on
      school days and free days. Internal consistency (Cronbach's alpha) of the PDSS-J
      was 0.77, and the test-retest reliability demonstrated by the intraclass
      coefficient was 0.88. Multivariate logistic regression analysis revealed that
      both short sleep duration and social jetlag were identified as factors associated
      with daytime sleepiness, after adjustment for age and sex. PDSS-J scores were
      significantly higher in the group with large social jetlag with or without
      sufficient sleep duration than in the group with sufficient sleep duration and
      small social jetlag. The PDSS-J is an important tool for assessing daytime
      sleepiness, given its ease of administration and robust psychometric properties.
      The impact of not only sleep loss but also social jetlag on daytime sleepiness
      among school-aged children and adolescents must be fully taken into account.

PMID- 27715325
TI  - Social jet lag, chronotype and body mass index in 14-17-year-old adolescents.
AB  - The relationship between sleep duration and obesity in adolescents is
      inconclusive. This may stem from a more complex relationship between sleep and
      obesity than previously considered. Shifts toward evening preferences, later
      sleep-wake times and irregular sleep-wake patterns are typical during adolescence
      but their relationship to body mass index (BMI) has been relatively unexplored.
      This cross-sectional study examined associations between sleep duration, midpoint
      of sleep and social jet lag (estimated from 7 days of continuous actigraphy
      monitoring), and morningness/eveningness with BMIs (BMI z-scores) and waist-to
      height ratios in 14-17-year-old adolescents. Seventy participants were recruited
      from ninth and tenth grades at a public high school. Participants'
      characteristics were as follows: 74% female, 75% post-pubertal, 36% Hispanic, 38%
      White, 22% Black, 4% Asian and 64% free/reduced lunch participants with a mean
      age of 15.5 (SD, 0.7). Forty-one percent of the participants were obese (BMI >=
      95th percentile); 54% were abdominally obese (waist-to-height ratio >= 0.5).
      Multivariable general linear models were used to estimate the association between
      the independent variables (school night sleep duration, free night sleep
      duration, midpoint of sleep (corrected), social jet lag and
      morningness/eveningness) and the dependent variables (BMI z-scores and waist-to
      height ratios). Social jet lag is positively associated with BMI z-scores (p <
      0.01) and waist-to-height ratios (p = 0.01). Midpoint of sleep (corrected) is
      positively associated with waist-to-height ratios (p = 0.01). After adjusting for
      social jet lag, school night sleep duration was not associated with waist-to
      height ratios or BMI z-scores. Morningness/eveningness did not moderate the
      association between sleep duration and BMI z-scores. Findings from this study
      suggest that chronobiological approaches to preventing and treating obesity may
      be important for accelerating progress in reducing obesity rates in adolescents.

PMID- 27715326
TI  - Effects of long-term exposure to 900 megahertz electromagnetic field on heart
      morphology and biochemistry of male adolescent rats.
AB  - The pathological effects of exposure to an electromagnetic field (EMF) during
      adolescence may be greater than those in adulthood. We investigated the effects
      of exposure to 900 MHz EMF during adolescence on male adult rats. Twenty-four 21
      day-old male rats were divided into three equal groups: control (Cont-Gr), sham
      (Shm-Gr) and EMF-exposed (EMF-Gr). EMF-Gr rats were placed in an EMF exposure
      cage (Plexiglas cage) for 1 h/day between postnatal days 21 and 59 and exposed to
      900 MHz EMF. Shm-Gr rats were placed inside the Plexiglas cage under the same
      conditions and for the same duration, but were not exposed to EMF. All animals
      were sacrificed on postnatal day 60 and the hearts were extracted for microscopic
      and biochemical analyses. Biochemical analysis showed increased levels of
      malondialdehyde and superoxide dismutase, and reduced glutathione and catalase
      levels in EMF-Gr compared to Cont-Gr animals. Hematoxylin and eosin stained
      sections from EMF-Gr animals exhibited structural changes and capillary
      congestion in the myocardium. The percentage of apoptotic myocardial cells in EMF
      Gr was higher than in either Shm-Gr or Cont-Gr animals. Transmission electron
      microscopy of myocardial cells of EMF-Gr animals showed altered structure of Z
      bands, decreased myofilaments and pronounced vacuolization. We found that
      exposure of male rats to 900 MHz EMF for 1 h/day during adolescence caused
      oxidative stress, which caused structural alteration of male adolescent rat heart
      tissue.

PMID- 27715327
TI  - Risks associated with significant head impact events in elite rugby union.
AB  - PRIMARY OBJECTIVES: To conduct video and statistical analysis on Rugby Union
      play, focusing mainly on the tackle, to establish the player to player
      configurations for significant direct head impacts and non-direct head impacts.
      RESEARCH DESIGN: Quantitative, observational cohort study. METHODS AND
      PROCEDURES: Video analysis of 52 significant direct head impacts (31 Tackle, 10
      Ruck, 7 Dive and 4 Ground) and 40 non-direct head impact tackles from 2014/15
      International Rugby Union matches. Relative risk, 95% CI and p-values were
      calculated for a range of tackle variables. MAIN OUTCOME AND RESULTS: Upper body
      tackles and lower body tackles accounted for 37% (19) and 23% (12) of cases,
      respectively, with the tackler as the head impacted player for 97% (30) of cases.
      The majority (81%) of tackle-related significant direct head impacts occurred in
      the second half of the game, with 63% of upper body tackle significant direct
      head impacts occurring in the final quarter. Tackler head placement and high
      speed tackles had statistical significance for causing tackle related significant
      direct head impacts as well as foot planting and difference in tackler and ball
      carrier mass for upper body tackles and ball carrier change in direction for
      lower body tackles. CONCLUSION: Tackle variables that statistically increased the
      risk of significant direct head impact were identified, which can aid player
      protection strategies.

PMID- 27715328
TI  - A review of implicit and explicit substance self-concept as a predictor of
      alcohol and tobacco use and misuse.
AB  - BACKGROUND: This paper provides an overview of the self-concept as it relates to
      substance use. Self-concept has a long history in psychological theory and
      research; however, substance self-concept (e.g., viewing one's self as a drinker
      or smoker) is an understudied area of research with the potential to expand
      existing conceptualizations of substance use, addiction, and prevention and
      treatment efforts, and should receive greater research attention. OBJECTIVES:
      First, we review and provide a theoretical framework of substance self-concept
      that draws from dual process models and distinguishes between implicit and
      explicit self-concept. Next, we summarize key findings related to substance use
      in the extant literature, focusing on alcohol and tobacco (smoking). RESULTS:
      Across both substances, there is converging evidence that substance self-concept
      is associated with substance use outcomes, including quantity and frequency of
      use and problems associated with use, and that change in substance self-concept
      is associated with recovery from substance misuse. Recommendations for the
      substance self-concept research agenda include routine assessment of substance
      self-concept, expanded use of implicit measures, investigation of moderators of
      substance self-concept, and targeting substance self-concept directly in
      prevention and intervention efforts. CONCLUSION: Ultimately, we suggest that
      substance self-concept is a promising, but understudied, construct. Greater
      research attention to substance self-concept could clarify its potential as an
      important risk factor for hazardous use and addiction as well as its utility as a
      prevention and treatment target.

PMID- 27715329
TI  - Preoperative Body Mass Index May Determine the Prognosis of Advanced Gastric
      Cancer.
AB  - Radical gastrectomy followed by adjuvant chemotherapy for advanced gastric cancer
      causes serious nutritional impairment. Our study evaluated the clinical impact of
      body mass index (BMI) on the long-term outcomes of advanced gastric cancer (stage
      II and III). We analyzed 211 cases of stage II and III gastric cancer between
      January 2005 and December 2010 at Chung-Ang University Hospital, Seoul, Korea.
      Patients were divided into four groups according to BMI: underweight, normal,
      overweight, and obese. In addition, we divided patients into two groups: BMI-High
      (BMI >= 23 kg/m2) vs. BMI-Low (BMI < 23 kg/m2). We assessed age, sex, tumor
      location, lymph node (LN) involvement, operation method, initial cancer stage,
      recurrence, and survival between the two groups. There was significant difference
      in overall survival (OS) between the underweight group and the other groups (P =
      0.005). The survival of the BMI-High group was better than that of the BMI-Low
      group. The rate of cancer-related death in the BMI-High group was significantly
      lower than that in the BMI-Low group (cancer-related death: BMI-Low 27% vs. BMI
      High 12.6%, P = 0.022). Our findings suggest that preoperative BMI may have an
      influence on the long-term outcomes of advanced gastric cancer after radical
      surgery and chemotherapy.

PMID- 27715330
TI  - Sex and Drugs and Starting School: Differences in Precollege Alcohol-Related
      Sexual Risk Taking by Gender and Recent Blackout Activity.
AB  - Research has demonstrated a link between alcohol use and multiple forms of risky
      sexual behavior, particularly among college-age individuals. Studies have also
      linked heavy alcohol use to other problems, such as impaired consciousness
      resulting from an alcohol-induced blackout, which may impact sexual decision
      making. However, research has rarely examined sexual risk taking (SRT) in
      relation to blackouts, nor has it examined this construct during the precollege
      transition (i.e., the interval of time between high school graduation and college
      matriculation). This study examined the intersection between alcohol-involved
      SRT, blackouts, and gender in a sample of precollege individuals with prior
      alcohol use (N = 229; 54% male, 63% White). Results indicated that, despite
      drinking less per occasion, women reporting recent blackouts were at increased
      risk for experiencing unwanted, unsafe, and regretted sexual behaviors compared
      to men with recent blackouts and their peers with no recent blackouts. Women with
      recent blackouts also reported differences in alcohol expectancies that may
      increase their risk for experiencing negative consequences while drinking,
      including higher social expectancies and lower negative expectancies of danger.
      Future directions for research and implications for precollege interventions are
      discussed.

PMID- 27715332
TI  - Comment on "Milham & Stetzer (2016) Tumor-specific frequencies and ocular
      melanoma." Electromag Biol Med http://dx.doi.org/10.1080/15368378.2016.1234390.

PMID- 27715331
TI  - Epidemiology and risk factors for tinnitus after leisure noise exposure in
      Flemish young adults.
AB  - OBJECTIVE: Young people regularly expose themselves to leisure noise and are at
      risk of acquiring tinnitus. This study examined the prevalence of leisure noise
      induced tinnitus among Flemish young adults as well as the relation with
      sociodemographic factors, health-related variables and attitudes and beliefs
      towards noise. DESIGN: A self-administered questionnaire was used to evaluate the
      presence of noise-induced tinnitus, the amount of leisure noise and attitudes
      towards noise and hearing protection. STUDY SAMPLE: 517 subjects between 18 and
      30 years were included. RESULTS: Temporary and chronic tinnitus occurred in 68.5%
      and 6.4% of the sample, respectively. Chronic tinnitus was more prevalent in male
      subjects and associated with more hearing-related symptoms. Furthermore, subjects
      with chronic tinnitus were more aware of the risks of noise and the importance of
      hearing protection. Finally, higher levels of leisure noise were independently
      associated with chronic tinnitus. CONCLUSIONS: Tinnitus is observed frequently in
      young adults. Results also indicate that persons with chronic tinnitus were
      exposed to a higher noise dose during their lives. Longitudinal studies may be
      useful to evaluate whether the experience of chronic tinnitus has led to
      behavioural changes. These findings further underpin the importance of educating
      youth about the risks of leisure noise exposure.

PMID- 27715333
TI  - A Qualitative Exploration of the Premigration Victimization Experiences of Sexual
      and Gender Minority Refugees and Asylees in the United States and Canada.
AB  - Progress in analyzing and interpreting the concepts of sexual orientation and
      gender identity in the context of refugee law has contributed to a rise in
      individuals seeking asylum in such countries as the United States and Canada.
      However, few studies have examined the victimization experiences of sexual- and
      gender-identity forced migrants prior to their arrival in North America. This
      qualitative study used thematic analysis to explore the premigration adult
      victimization experiences of 26 lesbian, gay, and transgender individuals who
      obtained refugee, asylee, or withholding-of-removal status in the United States
      or Canada based on persecution for their sexual orientation and/or gender
      identity. Participants originated from countries in Asia, Africa, the Caribbean,
      Eastern Europe, Latin America, and the Middle East. Analysis revealed the
      following themes: living on the edge, adopting concealment strategies, routine
      victimization, and protectors as perpetrators. Participants described living in a
      constant state of hypervigilance, and they adopted numerous strategies to protect
      themselves from victimization. Despite the use of such strategies, participants
      experienced victimization by community members and state actors, leaving them no
      choice but to flee to ensure their safety and well-being. Findings are discussed
      using the ecological framework outlined by the World Health Organization (WHO).
      The discussion concludes with implications for international policy and clinical
      practice.

PMID- 27715334
TI  - The relationship between chronotype and personality among patients with alcohol
      dependence syndrome: Pilot study.
AB  - The study investigates the distribution of chronotypes among alcohol-dependent
      subjects and the relationship between personality and chronotype. Fifty-eight
      alcohol-dependent patients and 29 age-matched healthy controls were studied using
      Oginska's Chronotype Questionnaire (ChQ), Eysenck's Personality Questionnaire -
      Revised (EPQ-R), Selzer's Michigan Alcoholism Screening Test (MAST) and a
      sociodemographic status questionnaire designed by the authors. The alcohol
      dependent patients tended to be morning type, based on the morningness
      eveningness ChQ scale, with a weakly marked rhythm, based on the distinctness ChQ
      scale. Preference towards morningness was associated with older age, but no
      relation between chronotype and severity of alcohol dependence was found. A high
      amplitude of the rhythm was associated with higher neuroticism. Therefore,
      despite being in the minority, patients with a distinct circadian rhythm (i.e.
      with a high amplitude) are at greater risk of mood and anxiety disorders and
      hence should be given special consideration.

PMID- 27715336
TI  - Clinical bioinformatics: emergence of a new laboratory discipline.

PMID- 27715335
TI  - Efficacy and Safety of Indacaterol/Glycopyrronium (IND/GLY) Versus
      Salmeterol/Fluticasone in Chinese Patients with Moderate-to-Severe Chronic
      Obstructive Pulmonary Disease: The Chinese Cohort from the LANTERN Study.
AB  - Inhaled indacaterol/glycopyrronium fixed-dose combination (IND/GLY) is approved
      in over 80 countries, including the EU, Japan, Australia and Switzerland and the
      US. The LANTERN study evaluated the efficacy of IND/GLY compared with inhaled
      long-acting beta2-agonist (LABA)/inhaled corticosteroid (ICS) or
      salmeterol/fluticasone (SFC) in patients with moderate-to-severe COPD with a
      history of <=1 exacerbation in the previous year. Here we present the efficacy
      and safety of IND/GLY versus SFC in the Chinese cohort from the LANTERN study.
      LANTERN was a 26-week, multicenter, randomized, double-blind, double-dummy,
      parallel-group study conducted in patients with moderate-to-severe COPD with a
      history of <=1 exacerbation in the previous year. The patients were randomized
      (1:1) to once-daily IND/GLY (110/50 MUg) or twice-daily SFC (50/500 MUg). The
      primary endpoint was non-inferiority of IND/GLY versus SFC in terms of trough
      FEV1. Of the total 744 patients randomized in the LANTERN study, 598 (80.4%) were
      from Mainland China and randomized to IND/GLY (n = 298) or SFC (n = 300), and 553
      (92.5%) completed the study. IND/GLY showed superiority over SFC with a
      statistically significant and clinically meaningful improvement in trough FEV1,
      FEV1 AUC0-4h, peak FEV1 and trough forced vital capacity (FVC) change from the
      baseline. Annualized rate of moderate or severe COPD exacerbations was
      significantly lower (43%) with IND/GLY compared with SFC (rate ratio: 0.57, p =
      0.015). Overall, adverse events were lower for IND/GLY (34.6%) versus SFC
      (43.1%). IND/GLY was superior in achieving bronchodilation versus SFC in a
      Chinese subgroup of patients from this study. Clinicaltrials.gov identifier:
      NCT01709903.

PMID- 27715337
TI  - An Exploratory Study Examining Current Assessment Supervisory Practices in
      Professional Psychology.
AB  - The extant literature reveals a considerable amount of research examining course
      work or technical training in psychological assessment, but a dearth of empirical
      research on assessment supervision. This study examined perspectives on current
      assessment supervisory practices in professional psychology through an online
      survey. Descriptive and qualitative data were collected from 125 survey
      respondents who were members of assessment-focused professional organizations and
      who had at least 1 year of supervision experience. Responses indicated a general
      recognition of the need for formal training in assessment supervision, ongoing
      training opportunities, and adherence to supervision competencies. Responses
      indicated more common use of developmental and skill-based models, although most
      did not regard any one model of assessment supervision as superior. Despite the
      recommended use of a supervision contract, only 65.6% (n = 80) of respondents use
      one. Discussion, directed readings, modeling, role-play, and case presentations
      were the most common supervisory interventions. Although conclusions are
      constrained by low survey response rate, results yielded rich data that might
      guide future examination of multiple perspectives on assessment supervision and
      ultimately contribute to curriculum advances and the development of supervision
      "best practices."

PMID- 27715338
TI  - N-Acetylcysteine and Desferoxamine Reduce Pulmonary Oxidative Stress Caused by
      Hemorrhagic Shock in a Porcine Model.
AB  - AIM OF THE STUDY: To investigate the pulmonary oxidative stress and possible
      protective effect of N-Acetylcysteine (NAC) and Desferoxamine (DFX)in a porcine
      model subjected to hemorrhagic shock. MATERIALS AND METHODS: Twenty-one pigs were
      randomly allocated to Group-A (sham, n = 5), Group-B (fluid resuscitation, n = 8)
      and Group-C (fluid, NAC and DFX resuscitation, n = 8). Groups B and C were
      subjected to a 40-min shock period induced by liver trauma, followed by a 60-min
      resuscitation period. During shock, the mean arterial pressure (MAP) was
      maintained at 30-40 mmHg. Resuscitation consisted of crystalloids (35 mL/kg) and
      colloids (18 mL/kg) targeting to MAP normalization (baseline values +/- 10%). In
      addition, Group-C received pretreatment with NAC 200 mg/kg plus DFX 2 g as
      intravenous infusions. Thiobarbituric Acid Reactive Substances (TBARS), protein
      carbonyls and glutathione peroxidase (GPx) activity were determined in lung
      tissue homogenates. Also, histological examination of pulmonary tissue specimens
      was performed. RESULTS: TBARS were higher in Group-B than in Group-A or Group-C:
      2.90 +/- 0.47, 0.57 +/- 0.10, 1.78 +/- 0.47 pmol/MUg protein, respectively (p <
      0.05). Protein carbonyls content was higher in Group-B than in Group-A or Group
      C: 3.22 +/- 0.68, 0.89 +/- 0.30, 1.95 +/- 0.54 nmol/mg protein, respectively (p >
      0.05). GPx activity did not differ significantly between the three groups (p >
      0.05). Lung histology was improved in Group-C versus Group-B, with less alveolar
      collapse, interstitial edema and inflammation. CONCLUSION: NAC plus DFX prevented
      the increase of pulmonary oxidative stress markers and protein damage after
      resuscitated hemorrhagic shock and had beneficial effect on lung histology.
      NAC/DFX combination may be used in the multimodal treatment of hemorrhagic shock,
      since it may significantly prevent free radical injury in the lung.

PMID- 27715340
TI  - Mechanisms behind Post-Thyroidectomy Hypocalcemia: Interplay of Calcitonin,
      Parathormone, and Albumin-A Prospective Study.
AB  - PURPOSE OF STUDY: Hypocalcemia after thyroidectomy is attributed to injury or
      ischemia to parathyroid glands. Transient hypocalcemia in thyroidectomy when
      parathyroids are preserved is not adequately explained. Release of calcitonin and
      hypoalbuminemia are two proposed reasons. Primary objective of this study was to
      find the change in calcitonin in the postoperative period after total
      thyroidectomy. Secondarily, hypocalcemia and its correlation with calcitonin,
      albumin, and parathormone were also studied. MATERIALS AND METHODS: This Cohort
      study was carried out at the general surgical department of a tertiary level
      teaching institution from April 2015 to December 2015. One hundred adult patients
      undergoing total thyroidectomy, with at least three parathyroids being preserved
      were included. Changes in calcium, calcitonin, albumin, and parathormone were
      studied based on preoperative levels and the values at 1, 6, 24, and 48 hr after
      surgery. RESULTS: Calcitonin increased at one hour after thyroidectomy and fell
      below preoperative levels subsequently. Parathormone showed a mild rise at one
      hour and normalized subsequently. Total calcium, corrected calcium, and albumin
      showed decline at one hour and recovered gradually over the next two days. At
      preoperative level, calcium had significant correlation with parathormone alone.
      Calcium levels at one hour had significant correlation with calcitonin. All post
      operative calcium levels had significant correlation with parathormone and the
      number of parathyroids preserved in situ without auto-transplantation.
      CONCLUSIONS: There is significant hypocalcemia within the first 24 hr after
      thyroidectomy, caused by calcitonin release and hypoalbuminemia. Preservation of
      maximum number of parathyroids in-situ can counter and normalize this
      hypocalcemia.

PMID- 27715339
TI  - Effect of Pirfenidone on Vascular Proliferation, Inflammation and Fibrosis in an
      Abdominal Adhesion Rat Model.
AB  - AIM: To study the efficacy of pirfenidone for prevention of postoperative
      adhesion formation in an adhesion rat model. MATERIALS AND METHODS: Eighteen
      female Wistar rats were subjected to right-sided parietal peritoneum and right
      uterine horn adhesion model. Rats were randomized into three groups: group 1
      (control) (closure of midline abdominal incision without any agent
      administration), group 2 (closure of incision after intraperitoneal
      administration of pirfenidone), and group 3 (closure of incision and only oral
      administration of pirfenidone for 14 days). Relaparotomy was performed 14 days
      after the first surgery. Effect of pirfenidone on adhesion formation was assessed
      on light microscopy by scoring vascular proliferation, inflammation, fibrosis,
      and collagen formation in the scarred tissue. Effect of pirfenidone on
      inflammation was assessed by measurement of transforming growth factor-beta and
      interleukin-17 levels in scarred tissue. RESULTS: The degree of vascular
      proliferation (1.32 +/- 0.39 versus 2.34 +/- 0.46, p < 0.001), inflammation (1.60
      +/- 0.70 versus 2.60 +/- 0.52, p < 0.01), and fibrosis (1.50 +/- 0.53 versus 2.40
      +/- 0.52, p < 0.01) were less prominent in group 2 compared to group 1,
      respectively. Only vascular proliferation was found to be less prominent in group
      3 compared to group 1 (1.60 +/- 0.42 versus 2.34 +/- 0.46, p < 0.01).
      Intraperitoneal and oral administration of pirfenidone reduced tissue levels of
      inflammatory markers (TGF-beta and IL-17) in parietal and visceral peritoneum
      compared to control group. Intraperitoneal administration of pirfenidone compared
      to oral administration was more effective in reducing tissue levels of
      inflammatory markers. CONCLUSION: Pirfenidone is an effective agent on the
      prevention of postoperative vascular proliferation, inflammation and fibrosis in
      scarred tissue particularly with intraperitoneal administration.

PMID- 27715341
TI  - Modulation of GLP-1 signaling as a novel therapeutic approach in the treatment of
      Alzheimer's disease pathology.
AB  - INTRODUCTION: Clinical studies suggest a link between peripheral insulin
      resistance and cognitive dysfunction. Post-mortem analyses of Alzheimer disease
      (AD) subjects revealed insulin resistance in the brain, suggesting a role of this
      condition in cognitive deficits observed in AD. In this review, we focus on the
      glucagon-like peptide-1 (GLP-1) signaling pathway, whose role in the brain is
      collecting increasing attention because of its association with insulin signaling
      activation. Areas covered: The role of GLP-1-mediated effects in the brain and
      how they are affected along the progression of AD pathology is discussed.
      Furthermore, we provide a comprehensive discussion about the use of GLP-1
      mimetics drugs, which have been developed as a treatment for T2DM but seem to
      possess a number of other physiological properties, including neuroprotective and
      anti-inflammatory effects, that may be useful to slow AD progression. Expert
      commentary: The repurposing of antidiabetic drugs for the modulation of brain
      insulin resistance in AD appears to be of great interest. The beneficial effects
      on synaptogenesis, neurogenesis, and cell repair as well as the reduction of the
      chronic inflammatory response, and most importantly the reduction of amyloid
      plaques in the brain indicate that these drugs have promise as novel treatments
      for AD.

PMID- 27715342
TI  - Comparison of threshold estimation in infants with hearing loss or normal hearing
      using auditory steady-state response evoked by narrow band CE-chirps and auditory
      brainstem response evoked by tone pips.
AB  - OBJECTIVE: The objective of this study is to compare air-conduction thresholds
      obtained with ASSR evoked by narrow band (NB) CE-chirps and ABR evoked by tone
      pips (tpABR) in infants with various degrees of hearing loss. DESIGN: Thresholds
      were measured at 500, 1000, 2000 and 4000 Hz. Data on each participant were
      collected at the same day. STUDY SAMPLE: Sixty-seven infants aged 4 d to 22
      months (median age = 96 days), resulting in 57, 52, 87 and 56 ears for 500, 1000,
      2000 and 4000 Hz, respectively. RESULTS: Statistical analysis was performed for
      ears with hearing loss (HL) and showed a very strong correlation between tpABR
      and ASSR evoked by NB CE-chirps: 0.90 (n = 28), 0.90 (n = 28), 0.96 (n = 42) and
      0.95 (n = 30) for 500, 1000, 2000 and 4000 Hz, respectively. At these
      frequencies, the mean difference between tpABR and ASSR was -3.6 dB (+/- 7.0), 
      5.2 dB (+/- 7.3), -3.9 dB (+/- 5.2) and -5.2 dB (+/- 4.7). Linear regression
      analysis indicated that the relationship was not influenced by the degree of
      hearing loss. CONCLUSION: We propose that dB nHL to dB eHL correction values for
      ASSR evoked by NB CE-chirps should be 5 dB lower than values used for tpABR.

PMID- 27715343
TI  - Curcumin reduces lung inflammation via Wnt/beta-catenin signaling in mouse model
      of asthma.
AB  - OBJECTIVES: Asthma is a chronic inflammatory, heterogeneous airway disease
      affecting millions of people around the world. Curcumin has been found to have
      anti-inflammatory and antifibrosis effects. Researchers reported that curcumin
      regulated Wnt/beta-catenin signaling in lots of cells. However, whether curcumin
      regulates the levels of Wnt/beta-Catenin signaling in lung tissues and DCs
      (dendritic cells) remains unclear. In this study, we assessed the effects of
      curcumin on DCs and asthma. METHODS: C57BL/6 mice immunized with OVA (ovalbumin)
      were challenged thrice with an aerosol of OVA every second day for 8 days.
      Dexamethasone or curcumin was administered intraperitoneally to OVA-immunized
      C57BL/6 mice on day 24 once a day for 9 days. Mice were analyzed for effects of
      curcumin on asthma, inflammatory cell infiltration and cytokine levels in lung
      tissue. DCs were isolated from mouse bone morrow. The surface markers CD40, CD86
      and CD11c of DCs was detected by FACS (fluorescence activated cell sorting) and
      the function of DCs was detected by mixed lymphocyte reaction. The expression of
      GSK-3beta and beta-catenin was detected by Western Blot. RESULTS: Results showed
      that OVA increased the number of inflammatory factors in BALF (bronchoalveolar
      lavage fluid), elevated lung inflammation scores in mice. Curcumin dose
      dependently reversed the alterations induced by OVA in the asthmatic mice.
      Curcumin activated Wnt/beta-catenin signaling pathway in DCs and asthmatic mouse
      lungs. CONCLUSIONS: Curcumin could influence the morphology and function of DCs,
      ease asthma symptom and inflammatory reaction through the activation of Wnt/beta
      catenin signaling. These results provide new evidence new evidence for
      application of curcumin on asthma.

PMID- 27715345
TI  - Discontinuation of modern hormonal contraceptives: an Italian survey.
AB  - OBJECTIVES: The aim of the study was to examine, in a sample of Italian women,
      the rate of discontinuation of use of hormonal contraception. METHODS: In a
      retrospective cross-sectional study, data were collected from a chart review of
      1809 women using or stopping the hormonal contraceptive prescribed by their
      physician. The name of the contraceptive and the reason for discontinuation were
      taken from the charts. The differences between the methods regarding reasons for
      discontinuation were analysed. RESULTS: Of the 1809 women examined, 34.9% had
      discontinued their hormonal contraception: 6.9% did so for non-method-related
      reasons, 20.5% due to minor side effects, 4.4% due to major side effects and 3.8%
      due to difficulties with compliance. Irregular bleeding, weight gain and headache
      were the main reasons reported for discontinuation. Pills containing 30 MUg or 20
      MUg ethinylestradiol (EE) and the vaginal ring were the most used contraceptive
      methods. Women using the vaginal ring discontinued less frequently compared with
      pill users (p < .005). Pills containing 20 MUg and 30 MUg EE had the same
      discontinuation rate. Venous thrombosis was the most frequently reported major
      side effect leading to discontinuation. CONCLUSION: About one-third of women who
      used modern hormonal contraceptives discontinued the method. Although the
      percentage of women who gave up as a result of minor side effects was lower than
      it used to be, and the use of low doses of EE by the vaginal route has decreased
      the rate of discontinuation, physicians should counsel women about the
      possibility of side effects and encourage them to seek advice before stopping.

PMID- 27715344
TI  - Pharmacokinetics and pharmacodynamics of ticagrelor in the treatment of cardiac
      ischemia.
AB  - INTRODUCTION: After acute coronary syndromes (ACS), the so-called dual
      antiplatelet therapy (DAPT), which usually consists of low-dose of aspirin in
      combination with a thienopyridine (clopidogrel, prasugrel) or with a
      cyclopentyltriazolopyrimidine (ticagrelor), reduces the risk of ischemic events.
      Ticagrelor, un particular, is an effective drug as it isn' a prodrug, doesn't
      require metabolic activation and demonstrates a rapid onset and faster offset of
      action. Areas covered: This article evaluates the pharmacokinetics, efficacy,
      safety and tolerability of ticagrelor during DAPT after ACS and its potential use
      beyond the canonical twelve months after PCI. The review discusses studies
      comparing: ticagrelor and clopidogrel (DISPERSE, DISPERSE-2, PLATO, RESPOND
      Trial, ONSET/OFFSET Trials), ticagrelor and placebo (PEGASUS TIMI 54 Trial).
      Expert opinion: For ACS patients, the PLATO trial showed that ticagrelor was
      superior to clopidogrel in the reduction of cardiovascular death, myocardial
      infarction and stroke. PEGASUS TIMI 54 showed that patients in whom ischemic
      events and cardiovascular death outweigh the risk of life-threatening bleeding,
      may benefit from prolonged ticagrelor-based dual antiplatelet therapy, over 12
      months. This strategy has been recently approved by the ACC/AHA guidelines.
      Further studies are needed to evaluate and eventually validate the role of the
      prolonged DAPT in patients treated with new generation stents.

PMID- 27715346
TI  - Suppression of RAGE and TLR9 by Ketamine Contributes to Attenuation of
      Lipopolysaccharide-Induced Acute Lung Injury.
AB  - The present study aimed to investigate the protective role of ketamine in
      lipopolysaccharide (LPS)-induced acute lung injury (ALI) by the inhibition of the
      receptor for advanced glycation end products (RAGE) and toll-like receptor 9
      (TLR9). ALI was induced in rats by intratracheal instillation of LPS (5 mg/kg),
      and ketamine (5, 7.5, and 10 mg/kg) was injected intraperitoneally 1 h after LPS
      administration. Meanwhile, A549 alveolar epithelial cells were incubated with LPS
      in the presence or absence of ketamine. After 24 h, bronchoalveolar lavage fluid
      (BALF) and lung tissue were collected. Ketamine posttreatment at doses of 5, 7.5,
      and 10 mg/kg decreased LPS-induced evident lung histopathological changes, lung
      wet-to-dry weight ratio, and lung myeloperoxidase activity. In addition,
      posttreatment with ketamine-inhibited inflammatory cells and inflammatory
      mediators including tumor necrosis factor-alpha, interleukin-6, and high-mobility
      group box 1 in BALF. Furthermore, we demonstrated that ketamine-inhibited LPS
      induced RAGE and TLR9 protein up-expressions and the phosphorylation of I-kappaB
      alpha and nuclear factor-kappaB (NF-kappaB) p65 in vivo and in vitro. The results
      presented here suggest that the protective mechanism of ketamine may be
      attributed partly to decreased production of inflammatory mediators through the
      inhibition of RAGE/TLR9-NF-kappaB pathway.

PMID- 27715347
TI  - Crucial Conversations: An interprofessional learning opportunity for senior
      healthcare students.
AB  - Clinical errors due to human mistakes are estimated to result in 400,000
      preventable deaths per year. Strategies to improve patient safety often rely on
      healthcare workers' ability to speak up with concerns. This becomes difficult
      during critical decision-making as a result of conflicting opinions and power
      differentials, themes underrepresented in many interprofessional initiatives.
      These elements are prominent in our interprofessional initiative, namely Crucial
      Conversations. We sought to evaluate this initiative as an interprofessional
      learning (IPL) opportunity for pre-licensure senior healthcare students, as a way
      to foster interprofessional collaboration, and as a method of empowering students
      to vocalise their concerns. The attributes of this IPL opportunity were evaluated
      using the Points for Interprofessional Education Score (PIPES). The University of
      the West of England Interprofessional Questionnaire was administered before and
      after the course to assess changes in attitudes towards IPL, relationships,
      interactions, and teamwork. Crucial Conversations strongly attained the
      principles of interprofessional education on the PIPES instrument. A total of 38
      volunteers completed the 16 hours of training: 15 (39%) medical rehabilitation,
      10 (26%) medicine, 7 (18%) pharmacy, 5 (13%) nursing, and 1 (2%) dentistry.
      Baseline attitude scores were positive for three of the four subscales, all of
      which improved post-intervention. Interprofessional interactions remained
      negative possibly due to the lack of IPL opportunities along the learning
      continuum, the hidden curriculum, as well as the stereotyping and hierarchical
      structures in today's healthcare environment preventing students from maximising
      the techniques learned by use of this interprofessional initiative.

PMID- 27715348
TI  - Plant-Based Nutraceutical Increases Plasma Catalase Activity in Healthy
      Participants: A Small Double-Blind, Randomized, Placebo-Controlled, Proof of
      Concept Trial.
AB  - Oxidative stress resulting from dietary, lifestyle and environmental factors is
      strongly associated with tissue damage and aging. It occurs when there is either
      an overproduction of reactive oxygen species (i.e., oxidants) or decreased
      bioavailability of antioxidants that can scavenge them. The objective of this 12
      week double-blind placebo-controlled study was to assess the efficacy of a
      nutraceutical at augmenting antioxidant status. Healthy adults (25-45 y) were
      randomized to either a treatment group (Product B, n = 23) or a placebo group
      (control, n = 20). No significant effect of Product B was observed for
      anthropometric variables or markers of glucose and lipid regulation. Biomarkers
      of oxidative stress were likewise not altered following the 12-week intervention.
      Plasma catalase concentrations were significantly elevated following 12 weeks of
      Product B as compared to the control group (+6.1 vs. -10.3 nmol/min/mL, p =
      0.038), whereas other measures of antioxidant capacity were not significantly
      different between the groups. Product B effectively augmented concentrations of
      the anti-aging antioxidant catalase in healthy adults.

PMID- 27715349
TI  - University and public health system partnership: A real-life intervention to
      improve asthma management.
AB  - OBJECTIVE: Asthma is under-diagnosed in many parts of the world. We aimed to
      assess the outcome of a capacitating program on asthma for non-specialist
      physicians and other healthcare professionals working in the public system in
      Ribeirao Preto, Brazil. METHODS: A group of 16 asthma specialists developed a one
      year capacitating program in 11 healthcare clinics in the Northern District of
      the city, which included lectures on asthma, training on inhalation device use
      and spirometry, and development of an asthma management protocol. Researchers
      visited one health unit 2-4 times monthly, working with doctors on patients'
      care, discussing cases, and delivering lectures. Asthma education was also
      directed to the general population, focusing on recognition of signs and symptoms
      and long-term treatment, including production of educational videos available on
      YouTube. Outcome measures were the records of doctors' prescriptions of
      individual asthma medications pre- and post-intervention. RESULTS: Prior to the
      program, 3205 units of inhaled albuterol and 2876 units of inhaled beclomethasone
      were delivered by the Northern District pharmacy. After the one-year program,
      there was increase to 4850 units (51.3%) for inhaled albuterol and 3526 units
      (22.6%) for inhaled beclomethasone. The albuterol increase followed the
      recommendation given to the non-specialist doctors by the asthma experts, that
      every patient with asthma should have inhaled albuterol as a rescue medication,
      by protocol. No increase was observed in other districts where no capacitating
      program was conducted. CONCLUSION: A systematic capacitating program was
      successful in changing asthma prescription profiles among non-specialist doctors,
      with increased delivery of inhaled albuterol and beclomethasone.

PMID- 27715350
TI  - A novel compartmentalised stent graft to isolate the perfusion of the abdominal
      organs.
AB  - Donation after cardiac death has been adopted to address the critical shortage of
      donor organs for transplant. Recovery of these organs is hindered by low blood
      flow that leads to permanent organ injury. We propose a novel approach to isolate
      the perfusion of the abdominal organs from the systemic malperfusion of the dying
      donor. We reasoned that this design could improve blood flow to organs without
      open surgery, while respecting the ethical principle that cardiac stress not be
      increased during organ recovery. Conditions within the stent were analysed using
      a computational fluid dynamics (CFD) method and validated on two prototypes in
      vitro. The hydrodynamic pressure drop across the stent was measured as 0.14-0.22
      mmHg, which is a negligible influence. Device placement studies were also
      conducted on swine model fluoroscopically. All these results demonstrated the
      feasibility of rapidly isolating the perfusion to abdominal organs using a
      compartmentalised stent graft design.

PMID- 27715351
TI  - Yeast beta-Glucan Modulates Inflammation and Waist Circumference in Overweight
      and Obese Subjects.
AB  - Increased inflammation occurs with excessive adiposity and yeast beta-glucan
      modulates immune responses. This study investigated the potential effect of yeast
      beta-glucan on inflammatory cytokines in overweight/obese people. A randomized,
      double blinded, placebo-controlled, clinical trial design enrolled 44
      overweight/obese participants with body mass index >=23 kg/m2, randomized to two
      groups receiving beta-glucan 477 mg/capsule (n = 22) or placebo (n = 22) orally
      for six weeks. At weeks one to two, participants received 1 beta-glucan or
      placebo capsule/day and at four weeks two tablets/day. Anthropometric changes,
      lipid profiles, liver and renal functions, and inflammatory cytokines were
      measured. beta-glucan reduced waist circumference (p = 0.037) and blood pressure
      (p = 0.006) compared with controls after six weeks of intervention. No
      statistical significance between groups was observed for triglyceride,
      cholesterol, lipid profile, liver and renal function, or energy and nutrient
      intake compared with controls at week six. beta-glucan increased interlukin-10
      (IL-10), an anti-inflammatory cytokine, by 23.97% from baseline at week two (p <
      0.001) and 31.12% at week six (p < 0.001) and was significantly increased
      compared with controls at week two (p < 0.001) until week six (p < 0.001). beta
      glucan reduced pro-inflammatory cytokines IL-6 at week six (p = 0.005) and tumor
      necrosis factor-alpha at week two (p = 0.037) compared with controls.
      Supplementation of yeast beta-glucan for six weeks modulated pro-cytokines that
      accelerate overweight/obese comorbidities and reduced blood pressure as well as
      waist circumference, the strong risk factors for cardiovascular disease, in
      overweight/obese subjects. Thus, beta-glucan might have the potential to decrease
      comorbid conditions associated with overweight/ obesity.

PMID- 27715352
TI  - Advancing interprofessional patient safety education for medical, nursing, and
      pharmacy learners during clinical rotations.
AB  - Clinical errors are common and can lead to adverse events and patient death.
      Health professionals must work within interprofessional teams to provide safe and
      effective care to patients, yet current curricula is lacking with regards to
      interprofessional education and patient safety. We describe the development and
      implementation of an interprofessional course aimed at medical, nursing, and
      pharmacy learners during their clinical training at a large academic medical
      centre. The course objectives were based on core competencies for
      interprofessional education and patient safety. The course was offered as
      recurring three 1-hour sessions, including case-based discussions and a mock root
      cause analysis. Forty-three students attended at least one session over a 7-month
      period. We performed a cross-sectional survey of participants to assess readiness
      for interprofessional learning and a before and after comparison of patient
      safety knowledge. All students reported a high level of readiness for
      interprofessional learning, indicating an interest in interprofessional
      opportunities. In general, understanding and knowledge of the four competency
      domains in patient safety was low before the course and 100% of students reported
      an increase in knowledge in these domains after participating in the course.

PMID- 27715353
TI  - Correlates of Condom Use Among Substance Using Older Seropositive MSM:
      Implications for Mental Health Practice.
AB  - The purpose of this study was to describe the correlates of condom use among a
      sample of N = 60 substance using seropositive men who have sex with (MSM). The
      mean age of the study participants was 52 ranging 50-75 years of age. Seventy
      percent of study participants reporting smoking marijuana, 62% using cocaine, 25%
      heroin, 37% alcohol, and 30% amphetamines. Among those reporting substance use,
      75% reported it was a hassle to use condoms, 42% indicated pleasure decreased
      with condom use, 72% indicated safer sex is boring, 72% reported the idea of
      using condoms is unappealing, 78% reported condoms ruined sex, and 71% said
      condoms interfered with romance. A multiple logistic regression analysis revealed
      low self-esteem, relationship status, attitudes towards condom use, and
      depression predicted condom use chi2 = 20.79, df = 6, rho =.002. The study
      findings have implications for mental health nursing practice with seropositive
      African American MSM.

PMID- 27715354
TI  - Validated questionnaires heighten detection of difficult asthma comorbidities.
AB  - OBJECTIVE: Multiple extra-pulmonary comorbidities contribute to difficult asthma,
      but their diagnosis can be challenging and time consuming. Previous data on
      comorbidity detection have focused on clinical assessment, which may miss certain
      conditions. We aimed to locate relevant validated screening questionnaires to
      identify extra-pulmonary comorbidities that contribute to difficult asthma, and
      evaluate their performance during a difficult asthma evaluation. METHODS: MEDLINE
      was searched to identify key extra-pulmonary comorbidities that contribute to
      difficult asthma. Screening questionnaires were chosen based on ease of use,
      presence of a cut-off score, and adequate validation to help systematically
      identify comorbidities. In a consecutive series of 86 patients referred for
      systematic evaluation of difficult asthma, questionnaires were administered prior
      to clinical consultation. RESULTS: Six difficult asthma comorbidities and
      corresponding screening questionnaires were found: sinonasal disease (allergic
      rhinitis and chronic rhinosinusitis), vocal cord dysfunction, dysfunctional
      breathing, obstructive sleep apnea, anxiety and depression, and gastro
      oesophageal reflux disease. When the questionnaires were added to the referring
      clinician's impression, the detection of all six comorbidities was significantly
      enhanced. The average time for questionnaire administration was approximately 40
      minutes. CONCLUSIONS: The use of validated screening questionnaires heightens
      detection of comorbidities in difficult asthma. The availability of data from a
      battery of questionnaires prior to consultation can save time and allow
      clinicians to systematically assess difficult asthma patients and to focus on
      areas of particular concern. Such an approach would ensure that all contributing
      comorbidities have been addressed before significant treatment escalation is
      considered.

PMID- 27715355
TI  - State-level medical and absenteeism cost of asthma in the United States.
AB  - OBJECTIVE: For medically treated asthma, we estimated prevalence, medical and
      absenteeism costs, and projected medical costs from 2015 to 2020 for the entire
      population and separately for children in the 50 US states and District of
      Columbia (DC) using the most recently available data. METHODS: We used multiple
      data sources, including the Medical Expenditure Panel Survey, U.S. Census Bureau,
      Kaiser Family Foundation, Medical Statistical Information System, and Current
      Population Survey. We used a two-part regression model to estimate annual medical
      costs of asthma and a negative binomial model to estimate annual school and work
      days missed due to asthma. RESULTS: Per capita medical costs of asthma ranged
      from $1,860 (Mississippi) to $2,514 (Michigan). Total medical costs of asthma
      ranged from $60.7 million (Wyoming) to $3.4 billion (California). Medicaid costs
      ranged from $4.1 million (Wyoming) to $566.8 million (California), Medicare from
      $5.9 million (DC) to $446.6 million (California), and costs paid by private
      insurers ranged from $27.2 million (DC) to $1.4 billion (California). Total
      annual school and work days lost due to asthma ranged from 22.4 thousand
      (Wyoming) to 1.5 million days (California) and absenteeism costs ranged from $4.4
      million (Wyoming) to $345 million (California). Projected increase in medical
      costs from 2015 to 2020 ranged from 9% (DC) to 34% (Arizona). CONCLUSION: Medical
      and absenteeism costs of asthma represent a significant economic burden for
      states and these costs are expected to rise. Our study results emphasize the
      urgency for strategies to strengthen state level efforts to prevent and control
      asthma attacks.

PMID- 27715356
TI  - The cost-effectiveness of 5-FU-SA in the treatment of actinic keratoses of the
      face and scalp in the UK secondary care setting.
AB  - OBJECTIVE: The objective of this analysis was to estimate the relative cost
      effectiveness of Actikerall 1 (5-FU-SA) vs cryotherapy in a secondary care
      setting in the UK, for lesion-directed treatment in patients with actinic
      keratoses (AK) of the face and scalp. METHODS: The model was a simple decision
      tree, with a 6-month time horizon. The perspective was that of the UK National
      Health Service (NHS). Modeled treatment effects included reported per-patient
      histological clearance and recurrence rates. Cost inputs comprised professional
      consultation time and cost of medication. Health-related utility estimation
      followed previously published methodology. Adverse events were not modeled. The
      key data and model structural assumptions followed expected UK practice. One-way
      and probabilistic sensitivity analyses were conducted to assess structural and
      parameter uncertainty. RESULTS: 5-FU-SA was found to be less costly (-L204) and
      more effective (+0.001 QALY) in base case and sensitivity analyses. In the
      probabilistic analysis there was 100% probability of being cost-effective over
      cryotherapy at L20,000 willingness to pay. Cost of professional time was a key
      driver of the model outcome. 5-FU-SA remained dominant across a range of scenario
      analyses, including exploration of assumptions around setting of care.
      LIMITATIONS: The time horizon of the analysis was short and data were not
      extrapolated beyond the duration of the clinical trial; however, this approach is
      consistent with likely follow-up of an AK patient. The clinical outcomes observed
      in the trial were based on a large proportion of cryotherapy patients undergoing
      an additional cycle of treatment; this may not occur or be required in an
      experienced secondary care setting. CONCLUSION: 5-FU-SA could be considered as a
      cost-effective choice for treatment of AK lesions of the face and scalp in
      secondary and mixed care settings in the UK. Use of 5-FU-SA in patients who would
      otherwise be managed with cryotherapy has the potential to result in cost
      savings.

PMID- 27715357
TI  - Factors related to parental age of first concern in toddlers with autism spectrum
      disorder.
AB  - PURPOSE: The age of first concern (AOC) of parents of children with autism
      spectrum disorders (ASD) has substantial implications for early diagnosis and
      intervention. The current study sought to determine the average AOC, what types
      of first concerns are most common, and what factors predict earlier AOC in
      toddlers with ASD. METHODS: This study analyzed the predictive influence of the
      type of concern, symptom severity, medical diagnoses, and other independent
      variables on AOC among toddlers with ASD using multiple regressions. RESULTS: The
      mean AOC was found to be 13.97 months (SD = 7.86). The most commonly reported
      first concern was speech/language. First concerns related to communication,
      speech/language predicted later AOC, while motor concerns predicted earlier AOC.
      CONCLUSIONS: Concerns that are more closely related to social communication
      deficits characteristic of ASD predicted later AOC. The implications of these
      findings on screening/assessment and intervention are discussed.

PMID- 27715358
TI  - Critical Review on Eliminating Endodontic Dental Infections Using Herbal
      Products.
AB  - The main purpose of a root canal treatment is to eliminate the bacteria and their
      products from the pulp space. Chemomechanical preparation (chemical-refers to
      irrigating solutions, i.e., either synthetic chemicals or herbal solutions and
      mechanical-refers to instrumentation of a root canals with endodontic files) of a
      root canal system plays a major role in obtaining the rationale of root canal
      treatment. Various synthetic chemicals known as endodontic irrigants play a major
      role in disinfection, but also have undesirable properties like allergic
      potential, toxicity, unacceptable taste, etc. Today there is a major change in
      trend towards the use of natural herbal medicines as a part of dental treatment
      due to its easy availability, less toxicity, and cost effectiveness. This article
      aims to provide a comprehensive review of various herbal endodontic irrigants
      evaluated for their effectiveness in the disinfection of a root canal system.
      This literature review is conducted using electronic databases "PubMed," "Google
      Scholar," and "Scopus," and articles were limited to those in the English
      language and published between 1980 and 2014.

PMID- 27715359
TI  - Topical 5% 5-fluorouracil in the treatment of multifocal basal cell carcinoma of
      the face: A novel chemotherapeutic approach.
AB  - To determine the safety and efficacy of topical 5-fluorouracil (5-FU) 5% ointment
      in treatment of non-syndromic multifocal basal cell carcinoma. A 55-year-old male
      patient, with 8 hours of daily sun exposure, having histologically proven and
      radiologically non-syndromic, multifocal basal cell carcinoma with involvement of
      6 sites on the face, was treated with topical 5-FU 5% ointment twice daily over
      all sites except the site involving lid margin to prevent corneal toxicity. Left
      lid lesion underwent wide surgical excision with 5-mm clear margins and
      reconstruction with nasal septal mucoperichondrium and local skin mobilization.
      Pharmacologic effects first appeared at 4 weeks and by 8 weeks, the lesions had
      scabbed and had fallen off with no induration but residual mild perilesional
      erythema. Patient had post-op histopathological clear margins and recovered
      uneventfully. No recurrence in 6 months. A topical 5-FU 5% ointment represents a
      paradigm shift in the treatment of BCC from invasive and disfiguring options
      (surgery and chemoradiotherapy) to cheap, convenient, effective, non-invasive,
      non-disfiguring topical chemotherapy. Topical 5% 5-FU is a safe and effective
      modality of treatment of superficial spreading multifocal basal carcinoma,
      especially lesions larger than 10 mm, where margins cannot be identified clearly
      and recurrent lesions.

PMID- 27715360
TI  - Going from "paper and pen" to ICT systems: Perspectives on managing the change
      process.
AB  - BACKGROUND: Lack of participation from staff when developing information and
      communication technologies (ICT) has been shown to lead to negative consequences
      and might be one explanation for failure. Management during development processes
      has rarely been empirically studied, especially when introducing ICT systems in a
      municipality context. OBJECTIVE: To describe and interpret experiences of the
      management during change processes where ICT was introduced among staff and
      managers in elderly care. DESIGN: A qualitative interpretive method was chosen
      for this study and content analysis for analyzing the interviews. RESULTS: "Clear
      focus-unclear process" demonstrated that focus on ICT solutions was clear but the
      process of introducing the ICT was not. "First-line managers receiving a system
      of support" gave a picture of the first-line manager as not playing an active
      part in the projects. First-line managers and staff described "Low power to
      influence" when realizing that for some reasons, they had not contributed in the
      change projects. "Low confirmation" represented the previous and present feelings
      of staff not being listened to. Lastly, "Reciprocal understanding" pictures how
      first-line managers and staff, although having some expectations on each other,
      understood each other's positions. CONCLUSIONS: Empowerment could be useful in
      creating an organization where critical awareness and reflection over daily
      practice becomes a routine.

PMID- 27715361
TI  - Association of emergency department albuterol dispensing with pediatric asthma
      revisits and readmissions.
AB  - INTRODUCTION: Although pediatric asthma continues to be a highly studied disease,
      data to suggest clear strategies to decrease asthma related revisits or
      readmissions is lacking. The purpose of our study was to assess the effect of
      emergency department (ED) direct dispensing of beta-agonist metered dose inhalers
      on pediatric asthma ED revisit and readmission rates. METHODS: We conducted a
      retrospective cohort study of pediatric patients discharged from the pediatric ED
      with a diagnosis of asthma. Our primary outcome measured the rate of asthma
      revisits to the ED or admissions to the hospital within 28 days. Logistic
      regression analysis was used to assess ED beta-agonist MDI dispensing and revisit
      and/or readmission as the outcome. RESULTS: A total of 853 patients met
      eligibility for inclusion in the study, with 657 enrolled in the Baseline group
      and 196 enrolled in the ED-MDI group. The Baseline group experienced a revisit
      and readmission rate of 7.0% (46/657) versus 2.6% (5/196) in the ED-MDI group, (p
      = 0.026). ED direct dispensing of MDIs was found to be independently associated
      with a decreased risk of revisit or readmission (odds ratio 0.37; 95% confidence
      interval 0.14-0.95). CONCLUSIONS: In our study, ED direct dispensing of beta
      agonist MDIs resulted in a reduction in 28-day revisit and readmission to the
      hospital. Further studies should be performed to evaluate the economic impact of
      reducing these revisits and readmissions against the costs of maintaining a
      dispensing program. Our findings may support modification of asthma programs to
      include dispensing MDIs from the emergency department.

PMID- 27715362
TI  - Cellular Infiltrate in Rheumatoid Arthritis-associated Paracentral Corneal
      Ulceration.
AB  - PURPOSE: To investigate an immunopathogenesis of central and paracentral corneal
      ulceration associated with rheumatoid arthritis. METHODS: Sparse infiltrating
      cells in the ulcer area were identified by immunohistochemistry applied to
      archived formalin fixed, paraffin embedded tissues that had been recovered from
      patients undergoing penetrating keratoplasty necessitated by rheumatoid
      associated central or paracentral corneal ulceration. RESULTS: Clinically, the
      ulcers presented as non-infiltrated lesions with a modicum of other ocular
      inflammation. Sparse T-lymphocytes were consistently identified in the
      subepithelial areas adjacent to the ulcer, with some neutrophils and macrophages
      in the stroma. B-lymphocytes were not detected. MHC Class II antigens reactivity
      was noted on some infiltrating cells and on corneal endothelium of two specimens.
      CONCLUSIONS: Immunohistochemistry of archival tissue facilitated detection and
      identification of sparse infiltrate in this infrequent corneal melting.
      Selective, consistent finding of T-lymphocyte infiltration in the ulcer area
      supports an immunopathogenesis of this clinical entity.

PMID- 27715363
TI  - Orbital medulloepithelioma in an adult patient: Radiation-induced second
      neoplasia?
AB  - Second cancers in survivors of hereditary retinoblastoma occur much more commonly
      than in the general population. This can be attributed both to the germline
      mutation of the RB gene and chemoradiation used for treatment of this paediatric
      cancer. Medulloepithelioma is an uncommon tumor of neuroectodermal origin, seen
      largely in the paediatric population and rarely reported in adults. Though the
      incidence of second malignancies is common in retinoblastoma, medulloepithelioma
      as a second malignancy in retinoblastoma survivors is rare, with only one case
      reported so far. Herein, we present a case of a 29-year-old patient presenting
      with medulloepithelioma of the right orbit, arising in the radiation field of
      previously treated retinoblastoma. This case was also peculiar in that though the
      origin of tumor was in the eyeball it had a very aggressive clinical course.

PMID- 27715364
TI  - Characterizing socially supportive environments relating to physical activity
      participation for young people with physical disabilities.
AB  - PURPOSE: To explore the experiences of young people with physical disabilities
      relating to social inclusion and physical activity, in order to describe the
      characteristics of social environments that support participation in physical
      activity. METHOD: An iterative, qualitative design employed in-depth, semi
      structured interviews with young people with physical disabilities aged 12-18 (n
      = 11). Data were analyzed using interpretive thematic analysis. RESULTS: Young
      people described several ways that their social environments help motivate and
      support them in their physical activity participation. These include providing:
      fair and equitable participation beyond physical accommodations; belonging
      through teamwork; and socially supported independence. CONCLUSIONS: Supportive
      social environments characterized by equitable participation, a sense of
      belonging, and opportunities for interdependence, play a critical role in
      promoting the health and well-being of young people with physical disabilities.
      These characteristics are important to consider in the design of both integrated
      and dedicated physical activity programs.

PMID- 27715366
TI  - Recurrent Aspergillus terreus Endophthalmitis from Focal Bronchiectasis.

PMID- 27715365
TI  - Rate of Retinal Detachment after Early Prophylactic Vitrectomy for Acute Retinal
      Necrosis.
AB  - PURPOSE: To compare the rate of retinal detachment after acute retinal necrosis
      in eyes that underwent early vitrectomy versus no early vitrectomy. METHODS:
      Charts of patients (61 eyes) who presented to Texas Retina Associates between
      January 1, 2006 and December 30, 2014 for acute retinal necrosis were reviewed.
      Charts with incomplete documentation or follow-up less than 6 months were
      excluded. Twenty-nine remaining eyes were divided into two groups: early
      vitrectomy and no early vitrectomy. Primary outcome measure was rate of retinal
      detachment. RESULTS: Out of 29 eyes, 12 underwent early vitrectomy within 30 days
      of diagnosis and 17 either underwent vitrectomy after 30 days or did not undergo
      prophylactic vitrectomy at all. Three out of 12 eyes (25%) developed retinal
      detachment in the early vitrectomy group versus 10 out of 17 eyes (59%) in the no
      early vitrectomy group (p = 0.076). CONCLUSIONS: Early vitrectomy within 30 days
      may prevent retinal detachment after acute retinal necrosis.

PMID- 27715367
TI  - A tunable local field potentials computer simulator to assess minimal
      requirements for phase-amplitude cross-frequency-coupling estimation.
AB  - The quantitative study of cross-frequency coupling (CFC) is a relevant issue in
      neuroscience. In local field potentials (LFPs), measured either in the cortex or
      in the hippocampus, how gamma-oscillation amplitude is modulated by changes in
      theta-rhythms-phase is thought to be important in memory formation. Several
      methods were proposed to quantify CFC, but reported evidence suggests that
      experimental parameters affect the results. Therefore, a simulation tool to
      support the determination of minimal requirements for CFC estimation in order to
      obtain reliable results is particularly useful. An approach to generate computer
      simulated signals having CFC intensity, sweep duration, signal-to-noise ratio
      (SNR), and multiphasic-coupling tunable by the user has been developed. Its
      utility has been proved by a study evaluating minimal sweep duration and SNR
      required for reliable theta-gamma CFC estimation from signals simulating LFP
      measured in the mouse hippocampus. A MATLAB(r) software was made available to
      facilitate methodology reproducibility. The analysis of the synthetic LFPs
      created by the simulator shows how the minimal sweep duration for achieving
      accurate theta-gamma CFC estimates increases as SNR decreases and the number of
      CFC levels to discriminate increases. In particular, a sufficient reliability in
      discriminating five different predetermined CFC levels is reached with 35-s sweep
      with SNR = 20, while SNR = 5 requires at least 140-s sweep.

PMID- 27715368
TI  - Improving social functioning and challenging behaviors in adolescents with ASD
      and significant ID: A randomized pilot feasibility trial of reciprocal imitation
      training in a residential setting.
AB  - There is a lack of effective social interventions for youths with ASD and co
      morbid intellectual disability (ID). A previous single-case design study
      indicated that reciprocal imitation training (RIT) may improve social interaction
      and challenging behavior in this population. The current pilot study examined the
      feasibility of conducting an RCT to investigate the effectiveness of RIT for
      improving social functioning and challenging behaviors in 20 adolescents with ASD
      and severe ID in a residential program. The assessment protocol was feasible. RIT
      was well-tolerated by the adolescents and implemented with fidelity by teaching
      staff. Preliminary findings indicate that treatment had moderate to large effects
      on social functioning and challenging behavior, with mixed findings for imitation
      skills. A larger RCT of RIT for this population is feasible and warranted.

PMID- 27715369
TI  - Drug interactions in HIV treatment: complementary & alternative medicines and
      over-the-counter products.
AB  - INTRODUCTION: Use of complementary and alternative medicines (CAMs) and over-the
      counter (OTC) medications are very common among HIV-infected patients. These
      products can cause clinically significant drug-drug interactions (DDIs) with
      antiretroviral (ARV) medications, thereby increasing risk for negative outcomes
      such as toxicity or loss of virologic control. Areas covered: This article
      provides an updated review of the different mechanisms by which CAM and OTC
      products are implicated in DDIs with ARV medications. Expert commentary: Much of
      the literature published to date involves studies of CAMs interacting with older
      ARV agents via the cytochrome P450 (CYP450) system. However, the HIV treatment
      and prevention arsenal is continually evolving. Furthermore, our elucidation of
      the role of non-CYP450 mediated DDIs with ARV medications is greatly increasing.
      Therefore, clinicians are well served to understand the various mechanisms and
      extent by which new ARV therapies may be involved in drug interactions with CAMs
      and OTC medications.

PMID- 27715370
TI  - An abbreviated scoring algorithm for the baby and infant screen for children with
      autism traits.
AB  - PURPOSE: Autism spectrum disorder (ASD) screening is recommended for all children
      aged 18-24 months. However, healthcare providers may be burdened with the
      responsibility of conducting these screens in addition to necessary services.
      Therefore, developing a time-efficient screener with sound psychometric
      properties is essential. METHODS: This study sought to update the abbreviated
      scoring algorithm of the Baby and Infant Screen for Children with aUtIsm Traits
      (BISCUIT) and increase its clinical utility. Six thousand and three children with
      ASD or atypical development enrolled in an early intervention program
      participated. RESULTS: A 6-item algorithm with a cutoff score of 3 was found to
      be optimal and yielded a sensitivity of 0.960 and a specificity of 0.864.
      CONCLUSION: Sensitivity and specificity estimates were similar to that of the
      complete BISCUIT-Part 1; thus, the 6-item algorithm can reliably differentiate
      children at-risk for ASD requiring further assessment. The algorithm appears to
      be a promising tool for early identification.

PMID- 27715371
TI  - Flow cytometric analysis of platelet cyclooxygenase-1 and -2 and surface
      glycoproteins in patients with immune thrombocytopenia and healthy individuals.
AB  - Immature platelets may contain more platelet enzymes such as cyclooxygenase (COX)
      1 and COX-2 than mature platelets. Patients with immune thrombocytopenia (ITP)
      have a higher fraction of immature platelets and can therefore be utilized as a
      biological model for investigating COX-1 and COX-2 platelet expression. The aims
      were to develop flow cytometric assays for platelet COX-1 and COX-2 and to
      investigate the COX-1 and COX-2 platelet expression, platelet turnover, and
      platelet glycoproteins in ITP patients (n = 10) compared with healthy individuals
      (n = 30). Platelet count and platelet turnover parameters (mean platelet volume
      (MPV), immature platelet fraction (IPF), and immature platelet count (IPC)) were
      measured by flow cytometry (Sysmex XE-5000). Platelet COX-1, COX-2, and the
      glycoproteins (GP)IIb, IX, Ib, Ia, and IIIa were all analyzed by flow cytometry
      (Navios) and expressed as median fluorescence intensity. COX analyses were
      performed in both whole blood and platelet rich plasma (PRP), whereas platelet
      glycoproteins were analyzed in whole blood only. ITP patients had significantly
      lower platelet count (55 * 109/L) than healthy individuals (240 * 109/L, p <
      0.01), but a higher MPV (p = 0.03) and IPF (p < 0.01). IPC was similar for the
      two groups (p = 0.74). PRP had significantly lower MPV (p < 0.01) and
      significantly higher platelet count and IPC (both p-values <0.03) when compared
      with whole blood. IPF was similar for PRP and whole blood (p = 0.18). COX-1
      expression was 10 times higher and COX-2 expression was 50% higher in PRP than in
      whole blood (pCOX-1 < 0.01, pCOX-2 < 0.01). Platelet COX-1 expression was higher
      in ITP patients than healthy individuals using whole blood (pCOX-1 < 0.01) and
      PRP, though this was nonsignificant in PRP (pCOX-1 = 0.17). In ITP patients,
      positive correlations were found between platelet turnover and COX-1 expression
      (all p-values <0.01, rho = 0.80-0.94), whereas healthy individuals showed
      significant though weaker correlations between platelet turnover and COX-1 and
      COX-2 expressions (all p-values <0.03, rho = 0.44-0.71). GPIIb, IX, and Ib
      expression was increased in ITP patients compared with healthy individuals (all p
      values < 0.03). GPIIb, IX, Ib, and IIIa showed positive correlations with
      platelet turnover in ITP patients (all p-values <0.02, rho = 0.71-0.94), but weak
      and nonsignificant correlations in healthy individuals (all p-values >0.14, rho =
      0.11-0.28). In conclusion, ITP patients expressed higher COX-1 and platelet
      glycoprotein levels than healthy individuals. COX-1 and platelet glycoproteins
      demonstrated positive correlations with platelet turnover in ITP patients. In
      healthy individuals, COX-1 and COX-2 expression correlated positively with
      platelet turnover. PRP was more sensitive compared with whole blood as regards
      determination of COX. Therefore, PRP is the recommended matrix for investigating
      COX-1 and COX-2 in platelets.

PMID- 27715372
TI  - Aggressive esthesioneuroblastoma with divergent differentiation: A taxonomic
      dilemma.
AB  - The authors describe an esthesioneuroblastoma (olfactory neuroblastoma) that
      occurred within the nasal cavity and brain in a 31-year-old man. Following
      excision, the tumor recurred in the left orbit and in mediastinal lymph nodes.
      Treatment included orbital excision and systemic chemotherapy. Histopathology
      showed a high-grade neuroepithelial tumor with positive immunohistochemical
      markers for neuroendocrine and epithelial components, an unusual combination
      raising issues concerning taxonomy.

PMID- 27715373
TI  - Cytomegalovirus Retinitis as the First Manifestation of Good Syndrome.

PMID- 27715374
TI  - Morphological and Functional Retinal Assessment in Epiretinal Membrane Surgery.
AB  - PURPOSE: To analyze functional and morphological findings after surgery for
      idiopathic epiretinal macular membrane (IEMM). MATERIALS AND METHODS: Twenty eyes
      of 20 patients affected by IEMM underwent 23-Gauge surgery. Morphological and
      functional examinations were assessed at baseline and at 30, 90, and 180 days
      after surgery. SD-OCT evaluated foveal morphology and thickness, photoreceptor
      inner/outer segment junction, and external limiting membrane. Functional
      assessment evaluated visual acuity, retinal sensitivity, and fixation patterns.
      Statistical analysis was performed with the Student's t test and Pearson
      correlation test. RESULTS: Mean central retinal thickness (CRT), visual acuity
      (VA), and retinal sensitivity (RS) at baseline were respectively 494.90 +/- 38.73
      um, 0.55 +/- 0.08 LogMAR, and 11.13+/-1.02; after surgery, at day 180, we
      observed a significant decrease in mean CRT to 326.90+/-32.68 um, an increase in
      mean VA to 0.33 +/- 0.05 LogMAR (p < 0.05), and in mean RS to 13.25 +/- 0.73 dB
      (p < 0.05). A stable fixation increased from 40% of patients at baseline to 75%
      of patients at day 180 (p < 0.05). DISCUSSION: IEMM surgery results in continuous
      improvement in visual function, not only at month one but also beyond month six,
      due to the progressive reduction of residual intraretinal edema and recomposition
      of retinal layers.

PMID- 27715375
TI  - Changes in the Macular Ganglion Cell Complex Thickness and Central Macular
      Thickness after Argon Laser Panretinal Photocoagulation.
AB  - PURPOSE: To evaluate the changes in the macular ganglion cell complex (GCC)
      thickness and central macular thickness (CMT) as measured by spectral domain
      optical coherence tomography (OCT) post-argon laser panretinal photocoagulation
      (PRP). METHODS: The medical records of 25 patients with proliferative diabetic
      retinopathy (PDR) who underwent PRP, 29 patients with non-proliferative diabetic
      retinopathy (NPDR), and 29 patients with diabetes but without diabetic
      retinopathy (DR) were analyzed. The patients who received PRP were followed up
      for one year. The follow-up measurements were evaluated at baseline, and months
      1, 6, and 12 post-argon laser PRP. The baseline values of CMT and GCC thickness
      were compared among the groups to assess changes with PRP therapy. RESULTS: The
      CMT gradually increased in months 1 and 6 and then decreased; however, it was
      significantly higher than the baseline value at month 12 in the PDR group post
      PRP. The GCC thickness also increased at months 1 and 6 in almost all segments of
      the macula, but at month 12 decreased to the baseline value. There was no
      correlation between the increasing thickness of the macula and change in the GCC
      thickness post-PRP period in the PDR group. In addition, no significant
      correlation was detected between the GCC thickness and best-corrected visual
      acuity during all follow-up visits. CONCLUSIONS: GCC thickness increased
      significantly until month 6 compared with baseline values in most of the macular
      segments post-PRP in the PDR group. The GCC thickness at month 12 was not
      different from the baseline thickness in any of the macular segments.

PMID- 27715376
TI  - 1.2% Rosuvastatin and 1.2% Atorvastatin Gel Local Drug Delivery and Redelivery in
      the Treatment of Class II Furcation Defects: A Randomized Controlled Clinical
      Trial.
AB  - BACKGROUND: Statins are one of the lipid-lowering drugs that help in reducing
      cholesterol levels in the body by specifically inhibiting 3-hydroxy-3
      methylglutaryl coenzyme A reductase, which is a rate-limiting enzyme for
      cholesterol synthesis. Rosuvastatin (RSV) and atorvastatin (ATV) have shown bone
      stimulatory and anti-inflammatory effects. The present study aims to explore
      efficacy of 1.2% RSV and 1.2% ATV gels as a local drug delivery and redelivery
      system adjunct to scaling and root planing (SRP) for treatment of Class II
      furcation defects. METHODS: Ninety patients with mandibular buccal Class II
      furcation defects were randomly allocated to three treatment groups: 1) SRP with
      placebo gel (group 1); 2) SRP with 1.2% RSV gel (group 2); and 3) SRP with 1.2%
      ATV gel (group 3). Clinical and radiographic parameters were recorded at baseline
      and after 6 months. Gels were redelivered at the respective sites at a 6-month
      recall appointment. All clinical and radiographic parameters were recorded again
      after 3 months (i.e., 9 months from baseline). RESULTS: Greater mean probing
      depth (PD) reduction and greater mean gain in relative vertical clinical
      attachment level (CAL) and relative horizontal CAL were seen in the RSV group
      than in the ATV group at 6 and 9 months. Significantly greater mean percentage of
      defect depth reduction (DDR) was found in the RSV group (30.80% +/- 8.35%, 41.86%
      +/- 6.76%) than in the ATV group (25.54% +/- 8.89%, 34.31% +/- 8.04%) at 6 and 9
      months, respectively. CONCLUSION: The RSV group shows significant improvement in
      all clinical parameters and significantly greater DDR compared with the ATV group
      in treatment of mandibular Class II furcation defects as an adjunct to SRP.

PMID- 27715378
TI  - Relationship between the sensation of activity limitation and the results of
      functional assessment in asthma patients.
AB  - OBJECTIVE: In asthma patients, the assessment of activity limitation is based on
      questions evaluating how limited the patient feels in their activities. However,
      the lack of functional data complicates the interpretation of the answers. We
      aimed to evaluate the intensity of relationships between the patient's perception
      of activity limitation and the results of several functional tests. METHODS:
      Twenty patients complaining of asthma exacerbation were invited to complete three
      scores (Chronic Respiratory Disease questionnaire, Asthma Control Questionnaire,
      Hospital Anxiety and Depression scale). They also underwent lung function
      measurements, a 6-minute walk test and a cardio-pulmonary exercise test. In
      addition, physical activity was studied by actigraphy. Spearman's rank
      correlation coefficients between the patient's perception of activity limitation
      and each of the other parameters were analysed. RESULTS: Five parameters were
      significantly correlated with the perception of activity limitation: ACQ question
      4, related to dyspnea (rs 0.74, p < 0.001); Emotion domain of the Chronic
      Respiratory Disease questionnaire (rs -0.57, p = 0.02); HAD anxiety (rs 0.48, p =
      0.032); HAD depression (rs 0.46, p = 0.041); ACQ question 6, related to reliever
      use (rs 0.46, p = 0.046). No parameters from the lung function test, 6MWT, CPET
      or actigraphy, were significantly correlated with the perception of activity
      limitation. CONCLUSIONS: In response to questions about limitation of activity,
      patients do not specifically answer mentioning physical limitation but rather the
      psychological burden associated with this constraint.

PMID- 27715377
TI  - Trunk deformity evaluation based on 3D measurements of front body surface
      landmarks in people with severe physical disabilities.
AB  - PURPOSE: To assess reliability and validity of a trunk deformity evaluation
      method expressed as rotational and lateral lean angles between the upper and the
      lower trunk and between the lower trunk and the pelvis using 3D positions of six
      front body surface landmarks. METHODS: Inter- and intra-rater reliabilities of
      the proposed method in adults with typical development (n = 22) were assessed,
      and its validity was also assessed through correlations between the Cobb angle
      and the analyzed trunk deformity parameters in adults with severe physical
      disabilities (n = 22). RESULTS: The mean differences between two raters and
      between the initial and second measures were within 2 degrees . Moderate
      correlations were found between the Cobb angle and both the upper and the lower
      trunk lateral lean angle and the upper trunk rotation angle. CONCLUSIONS: The
      proposed trunk deformity evaluation appears to be a reliable and valid approach
      for bedridden people with physical disabilities.

PMID- 27715379
TI  - The origins of major platelet receptor nomenclature.
AB  - The nomenclature of the major platelet receptors may appear complex, but in fact
      there are logical reasons why it developed in the way it did. In this short
      review, I describe the origins of this nomenclature, how it developed as more
      information became available and as relationships were established with receptors
      on other types of cells. Difficulties have also arisen with alternative
      nomenclature systems and the various equivalences with these are described and
      listed. There remain areas such as immunology and transfusion where the accepted
      nomenclature leaves something to be desired, but it is unlikely that major
      changes will occur.

PMID- 27715380
TI  - Ocular Manifestations, Conventional Fundus Fluorescein Angiographic Findings, and
      Relationship Between Angiographic Findings and Visual Acuity in Behcet's Disease.
AB  - PURPOSE: Evaluating the ocular manifestation and fundus fluorescein angiography
      (FA) findings of patients with Behcet's disease as well as the relationship
      between visual acuity and angiographic findings. METHODS: Retrospective chart
      review of patients with Behcet's disease seen at the Farabi Eye Hospital.
      RESULTS: Forty-six patients (92 eyes) with mean age of 33.41 +/- 10.67 were
      included. The most frequent presenting symptom and sign were reduced vision (76%)
      and uveitis (87%), respectively. Panuveitis was the most frequent type of uveitis
      (76%). Among patients with FA, vasculitis was the most common finding (87%) and
      it was significantly more severe among patients with visual acuity less than
      20/200. Macular leakage (P = 0.001), arterial narrowing (P = 0.000), and
      posterior retinal vasculitis (P = 0.002) on FA were all associated with worsening
      final visual acuity. CONCLUSION: The most common ocular findings in Behcet's
      disease were panuveitis and vasculitis. Location of vasculitis, arterial
      narrowing, and macular leakage on initial FA may predict visual prognosis.

PMID- 27715381
TI  - Meniscal biology in health and disease.
AB  - The knee is a fascinating yet complex joint. Researchers and clinicians agree
      that the joint is an organ comprised of highly specialized intrinsic and
      extrinsic tissues contributing to both health and disease. Key to the function
      and movement of the knee are the menisci, exquisite fibrocartilage structures
      that are critical structures for maintaining biological and biomechanical
      integrity of the joint. The biological/physiological functions of the menisci
      must be understood at the tissue, cellular and even molecular levels in order to
      determine clinically relevant methods for assessing it and influencing it. By
      investigating normal and pathological functions at the basic science level, we
      can begin to translate data to patients. The objective of this article is to
      provide an overview of this translational pathway so that progression toward
      improved diagnostic, preventative, and therapeutic strategies can be effectively
      pursued. We have thoroughly examined the pathobiological, biomarker, and imaging
      aspects of meniscus research. This translational approach can be effective toward
      optimal diagnosis, prevention, and treatment for the millions of patients who
      suffer from meniscal disorders each year.

PMID- 27715382
TI  - Comparing two methods to promote generalization of receptive identification in
      children with autism spectrum disorders.
AB  - PURPOSE: The purpose of our study was to compare the effects of serial and
      concurrent training on the generalization of receptive identification in children
      with autism spectrum disorders (ASD). METHODS: We taught one to three pairs of
      stimulus sets to nine children with ASD between the ages of three and six. One
      stimulus set within each pair was taught using concurrent training and the other
      using serial training. We alternated the training sessions within a multielement
      design and staggered the introduction of subsequent pairs for each participant as
      in a multiple baseline design. RESULTS: Overall, six participants generalized at
      least one stimulus set more rapidly with concurrent training whereas two
      participants showed generalization more rapidly with serial training.
      CONCLUSIONS: Our results differ from other comparison studies on the topic and
      indicate that practitioners should consider assessing the effects of both
      procedures prior to teaching receptive identification to children with ASD.

PMID- 27715383
TI  - Life in lights: Tracking mitochondrial delivery to lysosomes in vivo.
AB  - The past decade has seen an intensive and concerted research effort into the
      molecular regulation of mitophagy, the selective autophagy of mitochondria. Cell
      based studies have implicated mitophagy in the pathology of diverse conditions
      ranging from cancer to neurodegeneration. However, a definitive link between
      mitophagy and the etiology of human disease remains to be demonstrated. Moreover,
      we do not know how pervasive mammalian mitophagy is in vivo and fundamental
      questions remain unanswered. For example, is mitophagy common to all tissues
      under basal conditions or does it only occur in highly oxidative tissues under
      stress? This paucity of knowledge is largely due to a lack of experimentally
      tractable tools that can measure and monitor mitophagy in tissues. Our recent
      work describes the development of mito-QC, a mouse model to study mitophagy at
      single cell resolution in vivo.

PMID- 27715384
TI  - Allogeneic hematopoietic stem cell transplantation for nonmalignant hematologic
      disorders using chemotherapy-only cytoreductive regimens and T-cell-depleted
      grafts from human leukocyte antigen-matched or -mismatched donors.
AB  - Nonmalignant hematologic disorders (NMHD) of childhood comprise a variety of
      disorders, including acquired severe aplastic anemia and inherited marrow failure
      syndromes. Patients with high-risk NMHD without matched related donors fare
      poorly with allogeneic hematopoietic alternative donor stem cell transplantation
      (allo-HSCT) and are at high risk for developing graft-versus-host disease
      following unmodified grafts. The authors retrospectively analyzed data on 18
      patients affected by NMHD, lacking a human leukocyte antigen (HLA)-identical
      sibling donor, who underwent an alternative donor allo-HSCT at their institution
      between April 2005 and May 2013. Fifty percent of the patients had received prior
      immunosuppressive therapy, 72% had a history of infections, and 56% were
      transfusion dependent at the time of transplant. Cytoreduction included a
      combination of 3 of 5 agents: fludarabine, melphalan, thiotepa, busulfan, and
      cyclophosphamide. Grafts were T-cell depleted. All evaluable patients engrafted.
      Five died of transplant complications. The cumulative incidence of graft-versus
      host disease was 6%. No patient had recurrence of disease. Five-year overall
      survival was 77%. Age at transplant <6 years was strongly associated with better
      survival. Based on these results, transplant with chemotherapy-only cytoreductive
      regimens and T-cell-depleted stem cell transplants could be recommended for
      patients with high-risk NMHD, especially at a younger age.

PMID- 27715386
TI  - BECN1/Beclin 1 sorts cell-surface APP/amyloid beta precursor protein for
      lysosomal degradation.
AB  - The regulation of plasma membrane (PM)-localized transmembrane protein/receptor
      trafficking has critical implications for cell signaling, metabolism and
      survival. In this study, we investigated the role of BECN1 (Beclin 1) in the
      degradative trafficking of PM-associated APP (amyloid beta precursor protein),
      whose metabolism to amyloid-beta, an essential event in Alzheimer disease, is
      dependent on divergent PM trafficking pathways. We report a novel interaction
      between PM-associated APP and BECN1 that recruits macroautophagy/endosomal
      regulatory proteins PIK3C3 and UVRAG. We found that BECN1 promotes surface APP
      internalization and sorting predominantly to endosomes and endolysosomes. BECN1
      also promotes the targeting of a smaller fraction of internalized APP to LC3
      positive phagophores, suggesting a role for BECN1-dependent PM macroautophagy in
      APP degradation. Furthermore, BECN1 facilitates lysosomal degradation of surface
      APP and reduces the secretion of APP metabolites (soluble ectodomains, sAPP). The
      association between APP and BECN1 is dependent on the evolutionarily conserved
      domain (ECD) of BECN1 (amino acids 267-337). Deletion of a BECN1 ECD subregion
      (amino acids 285-299) did not impair BECN1- PIK3C3 interaction, PtdIns3K function
      or macroautophagy, but was sufficient to impair the APP-BECN1 interaction and
      BECN1's effects on surface APP internalization and degradation, resulting in
      increased secretion of sAPPs. Interestingly, both the BECN1-APP association and
      BECN1-dependent APP endocytosis and degradative trafficking were negatively
      regulated by active AKT. Our results further implicate phosphorylation of the
      BECN1 Ser295 residue in the inhibition of APP degradation by AKT. Our studies
      reveal a novel function for BECN1 in the sorting of a plasma membrane protein for
      endolysosomal and macroautophagic degradation.

PMID- 27715385
TI  - Progress of endocytic CHRN to autophagic degradation is regulated by RAB5-GTPase
      and T145 phosphorylation of SH3GLB1 at mouse neuromuscular junctions in vivo.
AB  - Endocytosed nicotinic acetylcholine receptors (CHRN) are degraded via
      macroautophagy/autophagy during atrophic conditions and are accompanied by the
      autophagic regulator protein SH3GLB1. The present study addressed the functional
      role of SH3GLB1 on CHRN trafficking and its implementation. We found an augmented
      ratio of total SH3GLB1 to threonine-145 phosphorylated SH3GLB1 (SH3GLB1:p
      SH3GLB1) under conditions of increased CHRN vesicle numbers. Overexpression of
      T145 phosphomimetic (T145E) and phosphodeficient (T145A) mutants of SH3GLB1, was
      found to either slow down or augment the processing of endocytic CHRN vesicles,
      respectively. Co-expression of the early endosomal orchestrator RAB5 largely
      rescued the slow processing of endocytic CHRN vesicles induced by T145E. SH3GLB1
      phosphomutants did not modulate the expression or colocalization of RAB5 with
      CHRN vesicles, but instead altered the expression of RAB5 activity regulators. In
      summary, these findings suggest that SH3GLB1 controls CHRN endocytic trafficking
      in a phosphorylation- and RAB5-dependent manner at steps upstream of
      autophagosome formation.

PMID- 27715387
TI  - Targeting neuronal MAPK14/p38alpha activity to modulate autophagy in the
      Alzheimer disease brain.
AB  - Dysregulated autophagic-lysosomal degradation of proteins has been linked to the
      most common genetic defect in familial Alzheimer disease, and has been correlated
      with disease progression in both human disease and in animal models. Recently, it
      was demonstrated that the expression of MAPK14/p38alpha protein is upregulated in
      the brain of APP-PS1 transgenic Alzheimer mouse and further that genetic
      deficiency of Mapk14 in the APP-PS1 mouse stimulates macroautophagy/autophagy,
      which then leads to reduced amyloid pathology via increasing autophagic-lysosomal
      degradation of BACE1. The findings resolve at least in the context of the APP-PS1
      mouse, prior conflicting in vitro observations that have implicated MAPK14 in
      autophagic processes, and indicate that inhibition of MAPK14 enzyme activity has
      potential as a therapeutic approach to mitigate a critical physiological defect
      within neurons of the Alzheimer disease brain. Moreover, the findings suggest
      that biomarkers of BACE1 activity could be utilized to evaluate the effects of
      MAPK14 inhibition and other autophagy-inducing therapeutic approaches in human
      clinical studies, thereby potentially facilitating the clinical development of
      such agents.

PMID- 27715388
TI  - Medical Malpractice in Uveitis: A Review of Clinical Entities and Outcomes.
AB  - PURPOSE: To guide risk management in uveitis. METHODS: Retrospective review of
      malpractice verdicts, rulings, and settlements. RESULTS: The WestLaw(r) database
      was reviewed for lawsuits related to uveitis in the United States from 1930-2014.
      Twenty-five cases met inclusion criteria, and 48% of these were infectious.
      Overall, 64% of outcomes favored the defendant ophthalmologist. The most common
      diagnoses were viral retinitis (28%), iritis (12%), syphilis (8%), and
      toxoplasmosis (8%). Seven suits (28%) were resolved by settlement, with mean
      adjusted indemnities of $724,302 (median, $409,390; range, $127,837-2,021,887).
      Two cases (8%) resulted in plaintiff verdict, with adjusted awards of $1,399,800
      and $630,799. CONCLUSIONS: Despite being a rare diagnosis, viral retinitis
      (especially acute retinal necrosis) is the most common clinical entity associated
      with litigation in uveitis and should be considered early. Educating patients
      about potential adverse events, early testing for syphilis, and maintaining a
      positive relationship may also minimize risk.

PMID- 27715389
TI  - Cell adhesion to anosmin via alpha5beta1, alpha4beta1, and alpha9beta1 integrins.
AB  - Anosmin is an extracellular matrix protein, and genetic defects in anosmin result
      in human Kallmann syndrome. It functions in neural crest formation, cell
      adhesion, and neuronal migration. Anosmin consists of multiple domains, and it
      has been reported to bind heparan sulfate, FGF receptor, and UPA. In this study,
      we establish cell adhesion/spreading assays for anosmin and use them for antibody
      inhibition analyses to search for an integrin adhesion receptor. We find that
      alpha5beta1, alpha4beta1, and alpha9beta1 integrins are needed for effective
      adhesive receptor function in cell adhesion and cell spreading on anosmin;
      adhesion is inhibited by both RGD and alpha4beta1 CS1-based peptides. This
      identification of anosmin-integrin adhesion receptors should facilitate studies
      of anosmin function in cell and developmental biology.

PMID- 27715390
TI  - Mice deficient in the Vici syndrome gene Epg5 exhibit features of retinitis
      pigmentosa.
AB  - Autophagy helps to maintain cellular homeostasis by removing misfolded proteins
      and damaged organelles, and generally acts as a cytoprotective mechanism for
      neuronal survival. Here we showed that mice deficient in the Vici syndrome gene
      Epg5, which is required for autophagosome maturation, show accumulation of
      ubiquitin-positive inclusions and SQSTM1 aggregates in various retinal cell
      types. In epg5-/- retinas, photoreceptor function is greatly impaired, and
      degenerative features including progressively reduced numbers of photoreceptor
      cells and increased numbers of apoptotic cells in the outer nuclear layer are
      observed, while the morphology of other parts of the retina is not severely
      affected. Downstream targets of the unfolded protein response (UPR), including
      the death inducer DDIT3/CHOP, and also levels of cleaved CASP3 (caspase 3), are
      elevated in epg5-/- retinas. Thus, apoptotic photoreceptor cell death in epg5-/-
      retinas may result from the elevated UPR. Our results reveal that Epg5-deficient
      mice recapitulate key characteristics of retinitis pigmentosa and thus may
      provide a valuable model for investigating the molecular mechanism of
      photoreceptor degeneration.

PMID- 27715391
TI  - Regulation of lysosomal phosphoinositide balance by INPP5E is essential for
      autophagosome-lysosome fusion.
AB  - Macroautophagy (autophagy) is a multistep intracellular degradation system.
      Autophagosomes form, mature, and ultimately fuse with lysosomes, where their
      sequestered cargo molecules are digested. In contrast to autophagosome formation,
      our knowledge of autophagosome-lysosome fusion is limited. In a recent study, we
      identified a novel regulator of autophagy, INPP5E (inositol polyphosphate-5
      phosphatase E), which is essential for autophagosome-lysosome fusion. INPP5E
      primarily functions in neuronal cells, and knockdown of the corresponding gene
      causes accumulation of autophagosomes by impairing fusion with lysosomes. Some
      INPP5E molecules localize at the lysosome, and both lysosomal localization and
      INPP5E enzymatic activity are crucial for autophagy. In addition, INPP5E
      decreases PtdIns(3,5)P2 levels on lysosomes, leading to activation of CTTN
      (cortactin) and stabilization of actin filaments, which are also essential for
      autophagosome-lysosome fusion. Mutations in INPP5E are causative for Joubert
      syndrome, a rare brain abnormality, and our results indicate that defects in
      autophagy play a critical role in pathogenesis.

PMID- 27715392
TI  - Contribution of semaphorins to the formation of the peripheral nervous system in
      higher vertebrates.
AB  - Semaphorins are a large family of proteins characterized by sema domains and play
      a key role not only in the formation of neural circuits, but in the immune
      system, angiogenesis, tumor progression, and bone metabolism. To date, 15
      semaphorins have been reported to be involved in the formation of the peripheral
      nervous system (PNS) in higher vertebrates. A number of experiments have revealed
      their functions in the PNS, where they act mainly as axonal guidance cues (as
      repellents or attractants). Semaphorins also play an important role in the
      migration of neurons and formation of sensory-motor connections in the PNS. This
      review summarizes recent knowledge regarding the functions of higher vertebrate
      semaphorins in the formation of the PNS.

PMID- 27715393
TI  - Expression of kindlin-3 in melanoma cells impedes cell migration and metastasis.
AB  - Kindlins are a small family of 4.1-ezrin-radixin-moesin (FERM)-containing
      cytoplasmic proteins. Kindlin-3 is expressed in platelets, hematopoietic cells,
      and endothelial cells. Kindlin-3 promotes integrin activation, clustering and
      outside-in signaling. Aberrant expression of kindlin-3 was reported in melanoma
      and breast cancer. Intriguingly, kindlin-3 has been reported to either positively
      or negatively regulate cancer cell metastasis. In this study, we sought to
      clarify the expression of kindlin-3 in melanoma cells and its role in melanoma
      metastasis. Two widely used metastatic mouse and human melanoma cell lines B16
      F10 and M10, respectively, were examined and found to lack kindlin-3 mRNA and
      protein expression. When kindlin-3 was ectopically expressed in these cells, cell
      migration was markedly reduced. These are attributed to aberrant Rac1 and RhoA
      activation and overt membrane ruffling. Our data demonstrate for the first time
      that despite its well established role as a positive regulator of integrin
      mediated cell adhesion, aberrant expression of kindlin-3 could lead to imbalanced
      RhoGTPases signaling that impedes rather than promotes cell migration.

PMID- 27715394
TI  - Orphan G protein-coupled receptor GPRC5A modulates integrin beta1-mediated
      epithelial cell adhesion.
AB  - G-Protein Coupled Receptor (GPCR), Class C, Group 5, Member A (GPRC5A) has been
      implicated in several malignancies. The underlying mechanisms, however, remain
      poorly understood. Using a panel of human cell lines, we demonstrate that
      CRISPR/Cas9-mediated knockout and RNAi-mediated depletion of GPRC5A impairs cell
      adhesion to integrin substrates: collagens I and IV, fibronectin, as well as to
      extracellular matrix proteins derived from the Engelbreth-Holm-Swarm (EHS) mouse
      sarcoma (Matrigel). Consistent with the phenotype, knock-out of GPRC5A correlated
      with a reduced integrin beta1 (ITGB1) protein expression, impaired
      phosphorylation of the focal adhesion kinase (FAK), and lower activity of small
      GTPases RhoA and Rac1. Furthermore, we provide the first evidence for a direct
      interaction between GPRC5A and a receptor tyrosine kinase EphA2, an upstream
      regulator of FAK, although its contribution to the observed adhesion phenotype is
      unclear. Our findings reveal an unprecedented role for GPRC5A in regulation of
      the ITGB1-mediated cell adhesion and it's downstream signaling, thus indicating a
      potential novel role for GPRC5A in human epithelial cancers.

PMID- 27715395
TI  - FoxO1-autophagy axis regulates lipid droplet growth via FSP27.

PMID- 27715397
TI  - Depletion of JMJD5 sensitizes tumor cells to microtubule-destabilizing agents by
      altering microtubule stability.
AB  - Microtubules play essential roles in mitosis, cell migration, and intracellular
      trafficking. Drugs that target microtubules have demonstrated great clinical
      success in cancer treatment due to their capacity to impair microtubule dynamics
      in both mitotic and interphase stages. In a previous report, we demonstrated that
      JMJD5 associated with mitotic spindle and was required for proper mitosis.
      However, it remains elusive whether JMJD5 could regulate the stability of
      cytoskeletal microtubules and whether it affects the efficacy of microtubule
      targeting agents. In this study, we find that JMJD5 localizes not only to the
      nucleus, a fraction of it also localizes to the cytoplasm. JMJD5 depletion
      decreases the acetylation and detyrosination of alpha-tubulin, both of which are
      markers of microtubule stability. In addition, microtubules in JMJD5-depleted
      cells are more sensitive to nocodazole-induced depolymerization, whereas JMJD5
      overexpression increases alpha-tubulin detyrosination and enhances the resistance
      of microtubules to nocodazole. Mechanistic studies revealed that JMJD5 regulates
      MAP1B protein levels and that MAP1B overexpression rescued the microtubule
      destabilization induced by JMJD5 depletion. Furthermore, JMJD5 depletion
      significantly promoted apoptosis in cancer cells treated with the microtubule
      targeting anti-cancer drugs vinblastine or colchicine. Together, these findings
      suggest that JMJD5 is required to regulate the stability of cytoskeletal
      microtubules and that JMJD5 depletion increases the susceptibility of cancer
      cells to microtubule-destabilizing agents.

PMID- 27715398
TI  - Survivin is a guardian of the intestinal stem cell niche and its expression is
      regulated by TGF-beta.
AB  - As an inhibitor of apoptosis (IAP) family member, Survivin is known for its role
      during regulation of apoptosis. More recently its function as a cell cycle
      regulator has become evident. Survivin was shown to play a pivotal role during
      embryonic development and is highly expressed in regenerative tissue as well as
      in many cancer types. We examined the function of Survivin during mouse
      intestinal organogenesis and in gut pathophysiology. We found high expression of
      Survivin in experimentally induced colon cancer in mice but also in colon tumors
      of humans. Moreover, Survivin was regulated by TGF-beta and was found to be
      highly expressed during mucosal healing following intestinal inflammation. We
      identified that expression of Survivin is essential early on in life, as specific
      deletion of Survivin in Villin expressing cells led to embryonic death around day
      12 post coitum. Together with our recent study on the role of Survivin in the gut
      of adult mice our data demonstrate that Survivin is an essential guardian of
      embryonic gut development and adult gut homeostasis protecting the epithelium
      from cell death promoting the proliferation of intestinal stem and progenitor
      cells.

PMID- 27715396
TI  - Understanding force-generating microtubule systems through in vitro
      reconstitution.
AB  - Microtubules switch between growing and shrinking states, a feature known as
      dynamic instability. The biochemical parameters underlying dynamic instability
      are modulated by a wide variety of microtubule-associated proteins that enable
      the strict control of microtubule dynamics in cells. The forces generated by
      controlled growth and shrinkage of microtubules drive a large range of processes,
      including organelle positioning, mitotic spindle assembly, and chromosome
      segregation. In the past decade, our understanding of microtubule dynamics and
      microtubule force generation has progressed significantly. Here, we review the
      microtubule-intrinsic process of dynamic instability, the effect of external
      factors on this process, and how the resulting forces act on various biological
      systems. Recently, reconstitution-based approaches have strongly benefited from
      extensive biochemical and biophysical characterization of individual components
      that are involved in regulating or transmitting microtubule-driven forces. We
      will focus on the current state of reconstituting increasingly complex biological
      systems and provide new directions for future developments.

PMID- 27715400
TI  - Genetic Variation in the 11beta-hydroxysteroid-dehydrogenase 1 Gene Determines
      NAFLD and Visceral Obesity.
AB  - CONTEXT/OBJECTIVE: Acute pharmacological inhibition of 11beta-hydroxysteroid
      dehydrogenase 1 (11beta-HSD1), which converts cortisone into the much more potent
      cortisol in peripheral tissues, results in reduction of total, visceral, and
      liver fat but not insulin resistance. We now investigated whether lifelong
      alterations of 11beta-HSD1 activity similarly affect these cardiometabolic risk
      parameters by studying single-nucleotide polymorphisms (SNPs) in the 11beta-HSD1
      coding gene (HSD11B1). DESIGN/METHODS: Liver fat content was measured by 1H
      magnetic resonance spectroscopy and total and visceral fat mass by 1H-magnetic
      resonance tomography in 327 subjects. Insulin sensitivity (IS) was estimated
      during an oral glucose tolerance test and the euglycemic, hyperinsulinemic clamp
      (n = 219). Nine SNPs covering the whole HSD11B1 gene were genotyped. RESULTS:
      After correction for multiple testing, liver fat content strongly correlated with
      three SNPs, rs2235543, rs12565406, and rs4844880 (P = .0002, P = .001, and P =
      .0009, respectively), independently of gender and age. There was a nominal
      association of these SNPs with hepatic IS but only of rs4844880 with whole-body
      IS. Subjects homozygous for the major allele had an adjusted odds ratio of 2.16
      (95% confidence interval [CI] 1.23-3.90) for rs2235543, 2.06 (95% CI 1.08-4.13)
      for rs12565406, and 1.95 (95% CI 1.13-3.49) for rs4844880 for having nonalcoholic
      fatty liver disease compared with carriers of the minor allele. Less strong
      associations of these SNPs with visceral fat mass were observed. In liver
      biopsies, carriers of the minor alleles of rs2235543 and rs12565406 had
      significantly lower HSD11B1 mRNA expression (n = 105, P = .034 and P = .0086,
      respectively). CONCLUSIONS: 11beta-HSD1 may be an important enzyme in the
      pathogenesis of fatty liver and visceral obesity and a promising target for their
      treatment.

PMID- 27715399
TI  - Proteolytic fragments of fibronectin function as matrikines driving the
      chemotactic affinity of prostate cancer cells to human bone marrow mesenchymal
      stromal cells via the alpha5beta1 integrin.
AB  - : The haematopoietic niche is contributed to by bone marrow-resident mesenchymal
      stromal cells (BM-MSCs) and subverted by prostate cancer cells. To study
      mechanisms by which BM-MSCs and prostate cancer cells may interact, we assessed
      the migration, invasion, adhesion and proliferation of bone-derived prostate
      cancer cells (PC-3) in co-culture with pluripotent human BM-MSCs. We observed a
      strong adhesive, migratory and invasive phenotype of PC-3 cells with BM- MSC-co
      culture and set out to isolate and characterize the bioactive principle. Initial
      studies indicated that chemotaxis was secondary to a protein residing in the
      >100kDa fraction. Size-exclusion chromatography (SEC) recovered peak activity in
      a high-molecular weight fraction containing thrombospondin-1 (TSP1). While TSP1
      immunodepletion decreased activity, put-back with purified TSP1 did not reproduce
      bioactivity. Further purification of the TSP1-containing high-molecular weight
      fraction of the BM-MSC secretome with heparin-affinity chromatography recovered
      bioactivity with highly restricted bands on polyacrylamide gel electrophoresis,
      determined by mass spectroscopy to be proteolytic fragments of fibronectin (FN).
      Put-back experiments with full-length FN permitted adhesion but failed to induce
      migration. Monospecific antibodies to FN blocked adhesion. Proteolytic cleavage
      of FN generated FN fragments which now induced migration. Neutralizing monoclonal
      antibodies to FN receptors alpha5 and beta1 integrins, and alpha5 knockdown
      specifically blocked migration and adhesion. CONCLUSION: Fibronectin fragments
      (FNFr) function as matrikines driving the chemotactic affinity of prostate cancer
      cells via the alpha5beta1 integrin. Taken together with the high-frequency of
      alpha5beta1 expression in disseminated prostate cancer cells in bone marrow
      aspirates from patients, the FNFr/FN-alpha5beta1 interaction warrants further
      study as a therapeutic target.

PMID- 27715401
TI  - Comparison of Early (2 Days) and Later (28 Days) Response of Adipose Tissue to
      Very Low-Calorie Diet in Obese Women.
AB  - CONTEXT: Beneficial metabolic effects of calorie restriction found in the early
      stage of hypocalorie diets may be caused by the modulation of metabolic and
      endocrine function of adipose tissue. OBJECTIVE: The objective of the study was
      to compare metabolic and inflammation-related characteristics of sc adipose
      tissue (SAAT) in the early (2 d) and later (28 d) phase of a very low calorie
      diet (VLCD). Design, Setting, Intervention, and Patients: Seventeen moderately
      obese premenopausal women followed an 800 kcal/d VLCD for 28 days. Anthropometric
      measurements, blood sampling, and a biopsy of SAAT were performed before the diet
      and after 2 and 28 days of the VLCD. MAIN OUTCOME MEASURE(S): mRNA expression of
      50 genes related to lipid metabolism, inflammation, and fibrosis were analyzed in
      SAAT. Secretion of adipokines was determined in SAAT explants and adipokines,
      fibroblast growth factor 21 (FGF21) and C-reactive protein were measured in
      plasma. RESULTS: In the early phase of the VLCD, the expression of lipolytic
      genes was increased, whereas the expression of lipogenic genes was significantly
      suppressed. The inflammatory markers in SAAT remained unchanged. At the later
      phase, expression of genes involved in lipogenesis and beta-oxidation was
      markedly suppressed, whereas the expression of inflammatory markers was
      increased. The changes of lipogenic genes after 28 days of the VLCD correlated
      with FGF21 changes. CONCLUSION: The early and later phases of a VLCD differ with
      respect to metabolic and inflammatory responses in SAAT. The expression changes
      in SAAT in the early phase of the VLCD could not explain the effect of short
      calorie restriction on the improvement of insulin sensitivity. An interplay of
      SAAT with liver function during VLCD mediated by FGF21 might be suggested.

PMID- 27715402
TI  - Effects of Cyclin Dependent Kinase 9 inhibition on zebrafish larvae.
AB  - CDK9 is a known regulator of cellular transcription, growth and proliferation.
      Small molecule inhibitors are currently being developed and assessed in clinical
      trials as anti-cancer drugs. The zebrafish embryo provides an ideal model to
      explore the effects of CDK9 inhibition in-vivo. This has not been adequately
      explored previously at the level of a whole organism. We have compared and
      contrasted the effects of pharmacological and molecular inhibition of CDK9 on
      somatic growth, apoptosis and cellular proliferation in zebrafish larvae between
      0 to 120 hours post fertilisation (hpf) using flavopiridol, a selective CDK9
      antagonist, and CDK9-targeting morpholino. We demonstrate that the inhibition of
      CDK9 diminishes cellular proliferation and increases apoptosis. Subsequently, it
      affects somatic growth and development of a number of key embryonic structures
      including the brain, heart, eye and blood vessels. For the first time, we have
      localized CDK9 at a subcellular level in whole-mounted larvae. This works shows,
      at a high-throughput level, that CDK9 clearly plays a fundamental role in early
      cellular growth and proliferation.

PMID- 27715403
TI  - Vitamin D decreases STAT phosphorylation and inflammatory cytokine output in T
      LGL leukemia.
AB  - Large granular lymphocyte leukemia (LGLL) is a rare incurable chronic disease
      typically characterized by clonal expansion of CD3+ cytotoxic T-cells. Two signal
      transducer and activator of transcription factors, STAT1 and STAT3, are
      constitutively active in T-LGLL. Disruption of this activation induces apoptosis
      in T-LGLL cells. Therefore, considerable efforts are focused on developing
      treatments that inhibit STAT activation. Calcitriol, the active form of vitamin
      D, has been shown to decrease STAT1 and STAT3 phosphorylation in cancer cell
      lines and autoimmune disease mouse models. Thus, we investigated whether
      calcitriol could be a valid therapeutic for T-LGLL. Calcitriol treatment of the
      TL-1 cell line (model of T-LGLL) led to decreased phospho-Y701 STAT1 and phospho
      Y705 STAT3 and increased vitamin D receptor (VDR) levels. Doses of 10 and 100 nM
      calcitriol also significantly decreased the inflammatory cytokine IFN-gamma in
      the TL-1 cell line. The overall cell viability did not change when the TL-1 cell
      line was treated with 0.1 to 1000 nM calcitriol. Studies with primary T-LGLL
      patient peripheral blood mononuclear cells showed that the majority of T-LGLL
      patients have detectable VDR and activated STATs in contrast to normal donor
      controls. Treatment of primary T-LGLL patient cells with calcitriol recapitulated
      findings from the TL-1 cell line. Overall, our results suggest that calcitriol
      may reprogram T-cells to decrease essential STAT activation and pro-inflammatory
      cytokine output. These data support further investigation into calcitriol as an
      experimental therapeutic for T-LGLL.

PMID- 27715404
TI  - Severe pediatric Graves orbitopathy in adolescents of African origin.
AB  - This article reports on two cases of severe pediatric Graves orbitopathy (GO) in
      two adolescents of African origin. Two black male adolescents presented with
      highly active GO and signs of beginning compressive optic neuropathy. Neither of
      them were smokers nor had a family history of GO. Besides urgent referral to
      pediatric endocrinologists, intravenous methylprednisolon pulse therapy was
      initiated. In spite of the fluctuating thyroid hormone levels in the initial
      phase of antithyroid therapy, intravenous steroid administration stopped the
      progression of malignant GO rapidly in both of our patients without any
      considerable side effects. Although the course of GO during childhood is
      considered to be mild, severe, sight threatening GO-requiring immunosuppression
      may occur at young age, as in the reported adolescent patients of African
      descent.

PMID- 27715406
TI  - Generalization and maintenance of a self-management program for drooling in
      children with neurodevelopmental disabilities: A second case series.
AB  - In this case series (n = 10) with a non-concurrent multiple baseline design, a
      self-management program was shown to be effective during inpatient training in
      eight participants with oral-motor problems and normal intelligence or mild
      intellectual disabilities. They were taught to perform a self-management routine
      and to remain dry for increasing time intervals. In addition, the program
      provided differential (self-) reinforcement of swallowing, controlling and wiping
      behavior, explicit formulation of motivational factors, instruction and feedback
      for parents and teachers, and continued practice after discharge. Generalization
      of the initial effect to the school setting was demonstrated in seven
      participants. Follow-up assessments demonstrated maintenance of positive results
      in four children up to 24 weeks, and for two other participants until 6 weeks
      after discharge. These results appeared to be relevant to parents and teachers.
      Teaching parents and teachers to implement the procedure enables them to support
      the child without professional supervision in the case of relapse.

PMID- 27715407
TI  - Septin complexes assemble during a kinetic window of opportunity.

PMID- 27715408
TI  - Cyclin D3: To translate or not to translate.

PMID- 27715405
TI  - Autophagy in Dictyostelium: Mechanisms, regulation and disease in a simple
      biomedical model.
AB  - Autophagy is a fast-moving field with an enormous impact on human health and
      disease. Understanding the complexity of the mechanism and regulation of this
      process often benefits from the use of simple experimental models such as the
      social amoeba Dictyostelium discoideum. Since the publication of the first review
      describing the potential of D. discoideum in autophagy, significant advances have
      been made that demonstrate both the experimental advantages and interest in using
      this model. Since our previous review, research in D. discoideum has shed light
      on the mechanisms that regulate autophagosome formation and contributed
      significantly to the study of autophagy-related pathologies. Here, we review
      these advances, as well as the current techniques to monitor autophagy in D.
      discoideum. The comprehensive bioinformatics search of autophagic proteins that
      was a substantial part of the previous review has not been revisited here except
      for those aspects that challenged previous predictions such as the composition of
      the Atg1 complex. In recent years our understanding of, and ability to
      investigate, autophagy in D. discoideum has evolved significantly and will surely
      enable and accelerate future research using this model.

PMID- 27715409
TI  - Community pharmacies as sites of adult vaccination: A systematic review.
AB  - Vaccine-preventable deaths among adults remain a major public health concern,
      despite continued efforts to increase vaccination rates in this population.
      Alternative approaches to immunization delivery may help address under
      vaccination among adults. This systematic review assesses the feasibility,
      acceptability, and effectiveness of community pharmacies as sites for adult
      vaccination. We searched 5 electronic databases (PubMed, EMBASE, Scopus,
      Cochrane, LILACS) for studies published prior to June 2016 and identified 47
      relevant articles. We found that pharmacy-based immunization services (PBIS) have
      been facilitated by state regulatory changes and training programs that allow
      pharmacists to directly provide vaccinations. These services are widely accepted
      by both patients and pharmacy staff, and are capable of improving access and
      increasing vaccination rates. However, political and organizational barriers
      limit the feasibility and effectiveness of vaccine delivery in pharmacies. These
      studies provide evidence to inform policy and organizational efforts that promote
      the efficacy and sustainability of PBIS.

PMID- 27715411
TI  - The impact of autophagy on the development of senescence in primary tubular
      epithelial cells.
AB  - Autophagy and senescence are 2 distinct pathways that are importantly involved in
      acute kidney injury and renal repair. Recent data indicate that the 2 processes
      might be interrelated. To investigate the potential link between autophagy and
      senescence in the kidney we isolated primary tubular epithelial cells (PTEC) from
      wild-type mice and monitored the occurrence of cellular senescence during
      autophagy activation and inhibition. We found that the process of cell isolation
      and transfer into culture was associated with a strong basal autophagic
      activation in PTEC. Specific inhibition of autophagy by silencing autophagy
      related 5 (Atg5) counteracted the occurrence of senescence hallmarks under
      baseline conditions. Reduced senescent features were also observed in Atg5
      silenced PTEC after gamma-irradiation and during H-Ras induced oncogenic
      senescence, but the response was less uniform in these stress models. Senescence
      inhibition was paralleled by better preservation of a mature epithelial phenotype
      in PTEC. Interestingly, treatment with rapamycin, which acts as an activator of
      autophagy, also counteracted the occurrence of senescence features in PTEC. While
      we interpret the anti-senescent effect of rapamycin as an autophagy-independent
      effect of mTOR-inhibition, the more specific approach of Atg5 silencing indicates
      that overactivated autophagy can have pro-senescent effects in PTEC. These
      results highlight the complex interaction between cell culture dependent stress
      mechanisms, autophagy and senescence.

PMID- 27715412
TI  - Bucrates lanista Rehn 1918 (Tettigoniidae: Conocephalinae): The First Record from
      the Brazilian Pantanal, the First Description of the Male, the First Karyotypic
      Report for the Genus, and the First Telomeric Hybridization of the Subfamily.
AB  - Bucrates lanista, the most southerly distributed species in the genus Bucrates
      Burmeister, was originally described from Brazil based on a female collected in
      the state of Rio Grande do Sul, but the species has not been recorded since 1918.
      In this work, we report that B. lanista inhabits the Pantanal Wetland in the
      state of Mato Grosso do Sul and, for the first time, describe the male.
      Individuals of B. lanista are gregarious and present a brown/green color
      dimorphism; this behavior and color variation are also observed in species of
      closely related genera. Individuals from the Pantanal vary slightly from those of
      Rio Grande do Sul. The karyotype was determined to be 2n? = 21 = 20 + X0 and 2n?
      = 22 = 20 + XX. The X chromosome is metacentric and the largest of the
      complement, and all of the autosomes are submetacentrics. All chromosomes solely
      present telomeric (TTAGG)n repeats at their ends, and some chromosomes present
      positive and negative DAPI bands.

PMID- 27715413
TI  - Complete Mitochondrial Reveals a New Phylogenetic Perspective on the Brackish
      Water Goby Mugilogobius Group (Teleostei: Gobiidae: Gobionellinae).
AB  - The Mugilogobius group consists of brackish water gobionellines widely
      distributed in the Indo-West Pacific region. Complete mitochondrial genome and
      morphological evidence was collected to estimate their phylogenetic relationship
      and taxonomic status. A total of 11 genera were sampled, including Brachygobius,
      Calamiana, Hemigobius, Mugilogobius, Pandaka, Pseudogobiopsis, Pseudogobius,
      Redigobius, Rhinogobius, Stigmatogobius, and Wuhanlinigobius, five of which were
      sequenced for the first time. A morphological phylogenetic tree was also
      reconstructed based on 35 characters. The molecular phylogenetic trees reveal
      that the Mugilogobius group contains four major clades. The present study also
      reveals that the adult male mouth size and forked sensory papillae row d can be
      considered as synapomorphies, and that the head pores on inter-orbital, anterior
      oculoscapular, and preopercular regions can be regarded as derived features among
      the Mugilogobius group. Furthermore, the absence of posterior oculoscapular pores
      may provide a clue for understanding the evolutionary history of the Mugilogobius
      group.

PMID- 27715414
TI  - Distribution of Dall's Porpoise, Phocoenoides dalli, in the North Pacific and
      Bering Sea, Based on T/S Oshoro Maru 2012 Summer Cruise Data.
AB  - Dall's porpoise (Phocoenoides dalli) is a small toothed cetacean, widely
      inhabiting the North Pacific Ocean and adjacent seas, between about 30 and 62
      degrees N; however, only limited studies of its ecology have been made in
      nearshore areas. A cetacean sighting survey lasting 60 days was conducted during
      the 2012 summer cruise of the T/S Oshoro Maru (Hokkaido University, Japan) in the
      North Pacific Ocean and Bering Sea. Based on this data, the distribution of
      Dall's porpoises and the factors controlling it in the pelagic habitat were
      investigated. A total of 808 individual Dall's porpoises in 166 groups were
      sighted during a total of 469.6 hr and 4946.6 nm observations. The cruise
      consisted of three legs and the average porpoise group size was significantly
      larger in Leg 1. The sightings were concentrated at water depths of less than
      1000 m and near eastern Aleutian passes. Sighting clusters were found on the 200
      m isobath of the southeastern Bering Sea continental slope. There was a peak in
      sightings where the sea surface temperature (SST) was relatively cold, between 5
      and 7 degrees C. Although similar track routes were taken in Leg 1 and Leg 3, the
      number of sightings per unit effort was larger in Leg 1. This difference may have
      arisen from the significant rise in SST as the season progressed. Relatively
      large group size found in this study might relate with prey abundance along the
      Aleutian Islands.

PMID- 27715415
TI  - Fine-Scale Genetic Differentiation in a Salamander Hynobius tokyoensis Living in
      Fragmented Urban Habitats in and Around Tokyo, Japan.
AB  - Salamanders are expected to differentiate genetically among local populations due
      to their low dispersal ability, and are potentially susceptible to loss of
      genetic diversity if the population is isolated by habitat fragmentation. The
      salamander Hynobius tokyoensis is a lowland lentic breeder and endemic to a
      narrow area of central Japan. In this urban area, H. tokyoensis habitats are
      extensively fragmented and several populations are threatened with extinction,
      but information on genetic divergence and loss of genetic diversity is scarce. We
      performed mitochondrial (cyt b) and microsatellite (five loci) DNA analyses of
      815 individuals from 46 populations in 12 regions across their entire
      distribution range. As a result, populations were clearly separated into northern
      and southern groups, and genetic differentiation among the 12 regions was also
      evident. Regional differentiation appears to be affected by a complex
      geographical history, but the genetic diversity of each population may have also
      been affected by recent habitat fragmentation. There were positive correlations
      between the mitochondrial and microsatellite DNA diversities. Some populations
      have lost genetic diversity in both mitochondrial and microsatellite DNAs; all
      such populations were at the peripheral edges of the species distribution range.
      Thus, even in attempts to restore genetic diversity in a small population by the
      transfer of outside individuals, efforts must be made to avoid genetic pollution.

PMID- 27715410
TI  - KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by
      decreasing CAST/calpastatin and ATG5 expression.
AB  - We have previously shown that Kaposi sarcoma-associated herpesvirus (KSHV)
      impairs monocyte differentiation into dendritic cells (DCs).
      Macroautophagy/autophagy has been reported to be essential in such a
      differentiating process. Here we extended these studies and found that the
      impairment of DC formation by KSHV occurs through autophagy inhibition. KSHV
      indeed reduces CAST (calpastatin) and consequently decreases ATG5 expression in
      both THP-1 monocytoid cells and primary monocytes. We unveiled a new mechanism
      put in place by KSHV to escape from immune control. The discovery of viral immune
      suppressive strategies that contribute to the onset and progression of viral
      associated malignancies is of fundamental importance for finding new therapeutic
      approaches against them.

PMID- 27715417
TI  - A Natural Population Derived from Species Hybridizationin the Drosophila
      ananassae Species Complexon Penang Island, Malaysia.
AB  - We surveyed natural population of the Drosophila ananassae species complex on
      Penang Island, Malaysia. Analyses of phenotypic traits, chromosome arrangements,
      molecular markers, and reproductive isolation suggest the existence of two
      species: D. ananassae and D. cf. parapallidosa. Molecular marker analysis
      indicates that D. cf. parapallidosa carries chromosome Y and 4 introgressions
      from D. ananassae. Thus, D. cf. parapallidosa seems to be a hybrid descendant
      that recently originated from a natural D. parapallidosa?* D. ananassae? cross.
      Furthermore, D. cf. parapallidosa behaves differently from authentic D.
      parapallidosa with respect to its reproductive isolation from D. ananassae.
      Premating isolation is usually seen in only the D. ananassae?* D. parapallidosa?
      cross, but we observed it in crosses of both directions between D. ananassae and
      D. cf. parapallidosa. In addition, hybrid males from the D. ananassae?* D.
      parapallidosa? cross are usually sterile, but they were fertile when D.
      ananassae? were mated with D. cf. parapallidosa ?. We attempted an artificial
      reconstruction of the hybrid species to simulate the evolutionary process(es)
      that produced D. cf. parapallidosa. This is a rare case of natural hybrid
      population in Drosophila and may be a useful system for elucidating speciation
      with gene flow.

PMID- 27715416
TI  - Hematophagous Flies Attracted to Frog Calls in a Preserved Seasonal Forest of the
      Austral Neotropics, with a Description of a New Species of Corethrella (Diptera:
      Corethrellidae).
AB  - The signaler-eavesdropper interaction has been investigated for a wide range of
      organisms, and although many flies feed on calling frogs, this dynamic has been
      addressed only poorly in the austral Neotropics. We investigated this interaction
      in southern Brazil using pairs of suction traps (acoustic + silent) broadcasting
      frog calls or an artificial white noise in ponds and streams. From 139 sessions,
      flies of the genera Corethrella (Corethrellidae), Forcipomyia (Ceratopogonidae)
      and Uranotaenia (Culicidae) were collected, including five Corethrella species,
      the most abundant of which was previously unknown and is formally described here.
      Additionally, we present the southernmost records of Corethrella lopesi, C.
      alticola and C. atricornis. Numbers of Forcipomyia midges and Uranotaenia
      mosquitoes did not differ between silent traps and traps broadcasting frog calls,
      and did not differ between white noise traps and adjacent silent traps. However,
      the number of female Corethrella was significantly higher in traps broadcasting
      calls of the pond-breeding frog P. aff. gracilis compared to adjacent silent
      traps; calls of this frog attracted the five Corethrella species and also
      collected significantly more female Corethrella than the white noise. By
      evaluating different taxa of flies and broadcasting different sounds, we
      demonstrated that Corethrella midges were attracted only to the acoustic cue of
      P. aff. gracilis calls, while Forcipomyia and Uranotaenia were captured in traps
      by chance. Our results suggest that female Corethrella feed on males of the
      common pond-breeding frog P. aff. gracilis in southern Brazil, and highlight the
      utility of frog call traps in revealing the diversity of Corethrella in the
      austral Neotropics.

PMID- 27715418
TI  - A New Deep-Sea Hydrothermal Vent Species of Ostracoda (Crustacea) from the
      Western Pacific: Implications for Adaptation, Endemism, and Dispersal of
      Ostracodes in Chemosynthetic Systems.
AB  - Deep-sea hydrothermal vent fields are among the most extreme habitats on Earth.
      Major research interests in these ecosystems have focused on the anomalous
      macrofauna, which are nourished by chemoautotrophic bacterial endosymbionts. In
      contrast, the meiofauna is largely overlooked in this chemosynthetic environment.
      The present study describes a new species, Thomontocypris shimanagai sp. nov.
      (Crustacea: Ostracoda), which was collected from the surface of colonies of
      neoverrucid barnacles and paralvinellid worms on the chimneys at the Myojin-sho
      submarine caldera. This is the first discovery of an ostracode from deep-sea
      hydrothermal vent environments in the western Pacific region. In addition to the
      species description, we discuss three aspects: 1) adaptation, 2) endemism, and 3)
      dispersal strategy of the hydrothermal vent ostracodes. Regarding these aspects,
      we conclude the following: 1) the new species may feed on sloughed-off tissues,
      mucus secretions, or fecal pellets of sessile organisms, rather than depend on
      chemoautotrophic bacteria as symbionts for energy; 2) as has been pointed out by
      other studies, Thomontocypris does not likely represent a vent-specific genus;
      however, this new species is considered to be endemic at the species level, as it
      has not been found outside of the type locality; and 3) this new species may have
      migrated from adjacent deep-sea chemosynthesis-based habitats, such as
      hydrothermal vents, with wood falls potentially having acted as stepping stones.

PMID- 27715419
TI  - Cosmopolitan or Cryptic Species? A Case Study of Capitella teleta (Annelida:
      Capitellidae).
AB  - Capitella teleta Blake et al., 2009 is an opportunistic capitellid originally
      described from Massachusetts (USA), but also reported from the Mediterranean, NW
      Atlantic, and North Pacific, including Japan. This putatively wide distribution
      had not been tested with DNA sequence data; intraspecific variation in
      morphological characters diagnostic for the species had not been assessed with
      specimens from non-type localities, and the species status of the Japanese
      population(s) was uncertain. We examined the morphology and mitochondrial COI
      (cytochrome c oxidase subunit I) gene sequences of Capitella specimens from two
      localities (Ainan and Gamo) in Japan. Specimens from Ainan and Gamo differed from
      C. teleta from Massachusetts in methyl-green staining pattern, shape of the
      genital spines, and shape of the capillary chaetae; we concluded that these
      characters vary intraspecifically. Species delimitation analyses of COI sequences
      suggested that worms from Ainan and Massachusetts represent C. teleta; these
      populations share a COI haplotype. The specimens from Gamo may represent a
      distinct species and comprise a sister group to C. teleta s. str.; we refer to
      the Gamo population as Capitella aff. teleta. The average Kimura 2-parameter
      (K2P) distance between C. teleta s. str. and C. aff. teleta was 3.7%. The COI
      data indicate that C. teleta actually occurs in both the NW Atlantic and NW
      Pacific. Given the short planktonic larval duration of C. teleta, this broad
      distribution may have resulted from anthropogenic dispersal.

PMID- 27715420
TI  - Historical Relationships among Wild Boar Populations of the Ryukyu Archipelago
      and Other Eurasian regions, as Inferred from Mitochondrial Cytochrome b Gene
      Sequences.
AB  - The Ryukyu wild boar (Sus scrofa riukiuanus) is an endemic, morphologically
      defined subspecies of the Eurasian wild boar (S. scrofa) found on five islands of
      the Ryukyu Archipelago (a group of small islands stretching from mainland Japan
      to Taiwan). Two hypothetical scenarios have been proposed regarding the origin of
      the current Ryukyu wild boar populations: 1) natural dispersal and 2)
      transportation and subsequent release by prehistoric humans. To test these two
      hypotheses, we compared the mitochondrial cytochrome b gene sequence (1140 base
      pairs) in 352 individual wild boar samples that included representatives of all
      five insular populations of the Ryukyu wild boar and populations of other
      conspecific subspecies in insular East and Southeast Asia and the Eurasian
      Continent. A total of 68 haplotypes were recognized, of which 12 were unique to
      the Ryukyu wild boar populations. The results of Bayesian phylogenetic analyses
      supported monophyly of the five Ryukyu populations (posterior probability value
      of 92), confirming the validity of the subspecies as a natural group. Coalescent
      analysis estimated the divergence times between the Ryukyu wild boar and the
      other conspecific subspecies as 144-465 thousand years ago (Kya), with a 95% HPD
      (highest posterior density) range of 51-837 Kya, and with no significant
      migration. Taking the broadly accepted date of initial human migration to the
      Ryukyus (no earlier than 50 Kya) into consideration, our results strongly suggest
      that the ancestral form of the Ryukyu wild boar first entered the Ryukyu
      Archipelago by natural dispersal prior to the arrival of prehistoric humans.

PMID- 27715421
TI  - Inheritance Pattern of Female Receptivity in Drosophila prolongata.
AB  - Choosiness, or female receptivity to copulation, is a critical component in
      female preference for a mating partner, as it functions at the final step in the
      mating process by determining whether she accepts copulation with a given male.
      In spite of its importance in the evolutionary process of male traits via sexual
      selection, little is known about the genetic variation and inheritance pattern of
      female receptivity. Drosophila prolongata shows a unique courtship behavior, leg
      vibration, which increases female receptivity to copulation. In the present
      study, we analyzed variation in female receptivity and its inheritance pattern in
      isofemale strains of D. prolongata using leg vibration as an index. There was a
      significant difference in female receptivity among the strains examined. A high
      receptivity phenotype was semi-dominantly expressed in F1 females of crosses
      between strains with low and high receptivity. Backcrossing F1 females to low
      receptivity strains resulted in a lower level of receptivity, suggesting that the
      high-receptivity phenotype is controlled by multiple genes with epistatic
      interactions. These results indicate a genetic basis of female receptivity,
      shedding light on the evolutionary process of sexual selection in D. prolongata.

PMID- 27715422
TI  - Molecular Cloning of Ghrelin and Characteristics of Ghrelin-Producing Cells in
      the Gastrointestinal Tract of the Common Marmoset (Callithrix jacchus).
AB  - Ghrelin was first isolated from human and rat as an endogenous ligand for the
      growth hormone secretagogue receptor (GHS-R). In the present study, we determined
      the ghrelin cDNA sequence of the common marmoset (Callithrix jacchus), a small
      bodied New World monkey, and investigated the distribution of ghrelin-producing
      cells in the gastrointestinal tract and localization profiles with somatostatin
      producing cells. The marmoset ghrelin cDNA coding region was 354 base pairs, and
      showed high homology to that in human, rhesus monkey, and mouse. Marmoset ghrelin
      consists of 28 amino acids, and the N-terminal region is highly conserved as
      found in other mammalian species. Marmoset preproghrelin and mature ghrelin have
      86.3% and 92.9% homology, respectively, to their human counterparts. Quantitative
      RT-PCR analysis showed that marmoset ghrelin mRNA is highly expressed in the
      stomach, but it is not detected in other tissues of the gastrointestinal tract.
      In addition, a large number of ghrelin mRNA-expressing cells and ghrelin
      immunopositive cells were detected in the mucosal layer of the stomach, but not
      in the myenteric plexus. Moreover, all the ghrelin cells examined in the stomach
      were observed to be closed-type. Double staining showed that somatostatin
      immunopositive cells were not co-localized with ghrelin-producing cells; however,
      a subset of somatostatin-immunopositive cells is directly adjacent to ghrelin
      immunopositive cells. These findings suggest that the distribution of ghrelin
      cells in marmoset differs from that in rodents, and thus the marmoset may be a
      more useful model for the translational study of ghrelin in primates. In
      conclusion, we have clarified the expression and cell distribution of ghrelin in
      marmoset, which may represent a useful model in translational study.

PMID- 27715423
TI  - Regeneration of Murine Hair Follicles is Inhibited by Low-Dose-Rate Gamma
      Irradiation.
AB  - To determine whether the effects of low-dose-rate gamma (gamma) irradiation are
      identifiable in the regeneration of murine hair follicles, we irradiated whole
      bodies of C57BL/10JHir mice in the first telogen phase of the hair cycle with
      137Cs gamma-rays. The mice were examined for effects on hair follicles, including
      number, morphology, and pigmentation in the second anagen phase. Effects of gamma
      radiation on melanocyte stem cells were also investigated by the indirect
      immunolabeling of tyrosinase-related protein 2 (TRP2). Irradiated skin showed a
      decrease in hair follicle density and the induction of curved hair follicles
      along with the presence of white hairs and hypopigmented hair bulbs. There was a
      small, but not significant, change in the number of TRP2-positive melanocyte stem
      cells in the hair bulge region of the irradiated skin. These results suggest that
      low-dose rate gamma-irradiation does not deplete melanocyte stem cells, but can
      damage stem cells and progenitors for both keratinocytes and melanocytes, thereby
      affecting the structure and pigmentation of regenerated hair follicles in the 2nd
      anagen phase.

PMID- 27715424
TI  - Population Structure of the Raccoon Dog on the Grounds of the Imperial Palace,
      Tokyo, Revealed by Microsatellite Analysis of Fecal DNA.
AB  - The raccoon dog (Nyctereutes procyonoides, Canidae, Carnivora) is highly
      adaptable to urban environments. Populations of carnivorans inhabiting urban
      areas sometimes differ ecologically and genetically from those in rural areas.
      However, there is little information on urban raccoon dogs. This study focused on
      raccoon dog populations in Tokyo, one of the most highly urbanized cities in the
      world. We examined the genotypes of 10 microsatellites for 101 fecal samples from
      raccoon dogs inhabiting the grounds of the Imperial Palace, a green space in
      central Tokyo. We successfully genotyped 58 samples originating from 31
      individuals. We also analyzed muscle tissue samples from raccoon dogs from the
      grounds of the Imperial Palace, the Akasaka Imperial Grounds (a green space close
      to the Imperial Palace), and the surrounding urban area, and then investigated
      the genetic structure and diversity of these populations, and the genetic
      differentiation among them. The population on the grounds of the Imperial Palace
      was genetically differentiated from that in the Akasaka Imperial Grounds,
      suggesting that the roads and buildings act as barriers to gene flow. In
      addition, the population on the grounds of the Imperial Palace showed greater
      genetic difference from that in the surrounding area than that in the Akasaka
      Imperial Grounds. We speculate that the moats around the Imperial Palace restrict
      individual ranges within the palace grounds and limit migration and gene flow to
      other areas.

PMID- 27715425
TI  - Production of Knockout Mutants by CRISPR/Cas9 in the European Honeybee, Apis
      mellifera L.
AB  - The European honeybee (Apis mellifera L.) is used as a model organism in studies
      of the molecular and neural mechanisms underlying social behaviors and/or
      advanced brain functions. The entire honeybee genome has been sequenced, which
      has further advanced molecular biologic studies of the honeybee. Functions of
      genes of interest, however, remain largely to be elucidated in the honeybee due
      to the lack of effective reverse genetic methods. Moreover, genetically modified
      honeybees must be maintained under restricted laboratory conditions due to legal
      restrictions, further complicating the application of reverse genetics to this
      species. Here we applied CRISPR/Cas9 to the honeybee to develop an effective
      reverse genetic method. We targeted major royal jelly protein 1 (mrjp1) for
      genome editing, because this gene is predominantly expressed in adult workers and
      its mutation is not expected to affect normal development. By injecting sgRNA and
      Cas9 mRNA into 57 fertilized embryos collected within 3 h after oviposition, we
      successfully created six queens, one of which produced genome-edited male
      offspring. Of the 161 males produced, genotyping demonstrated that the genome was
      edited in 20 males. All of the processes necessary for producing these genome
      edited queens and males were performed in the laboratory. Therefore, we developed
      essential techniques to create knockout honeybees by CRISPR/Cas9. Our findings
      also suggested that mrjp1 is dispensable for normal male development, at least
      till the pupal stage. This new technology could pave the way for future
      functional analyses of candidate genes involved in honeybee social behaviors.

PMID- 27715426
TI  - Effects of Caffeine on Olfactory Learning in Crickets.
AB  - Caffeine is a plant-derived alkaloid that is generally known as a central nervous
      system (CNS) stimulant. In order to examine the effects of caffeine on higher CNS
      functions in insects, we used an appetitive olfactory learning paradigm for the
      cricket Gryllus bimaculatus. Crickets can form significant long-term memories
      (LTMs) after repetitive training sessions, during which they associate a
      conditioned stimulus (CS: odor) with an unconditioned stimulus (US: reward).
      Administration of hemolymphal injections of caffeine established LTM after only
      single-trial conditioning over a wide range of caffeine dosages (1.6 uug/kg to 39
      mg/kg). We investigated the physiological mechanisms underlying this enhancement
      of olfactory learning performance pharmacologically, focusing on three major
      physiological roles of caffeine: 1) inhibition of phosphodiesterase (PDE), 2)
      agonism of ryanodine receptors, and 3) antagonism of adenosine receptors.
      Application of drugs relevant to these actions resulted in significant effects on
      LTM formation. These results suggest that externally applied caffeine enhances
      LTM formation in insect olfactory learning via multiple cellular mechanisms.

PMID- 27715427
TI  - Tick-borne encephalitis: What travelers should know when visiting an endemic
      country.
AB  - Tick-borne encephalitis (TBE) is an acute febrile illness with neurological
      manifestations that is prevalent in forested areas of moderate climate in Europe
      and Asia. TBE virus is transmitted by ticks and rarely by unpasteurized milk and
      dairy products. The disease burden is attributed mainly to resulting long-term
      disability, especially in individuals over 50 y of age. Currently, there is no
      causative treatment, but a very effective vaccination is available with a good
      safety profile. The vaccination requires 3 basic doses to be fully effective and
      regular boosters afterwards. An accelerated vaccination schedule enables a
      patient to reach reasonably protective titres within 3 to 4 weeks from the first
      injection. The risk of travel-related TBE is estimated to be less than the risk
      of acquiring typhoid fever while visiting highly endemic regions in South Asia,
      but more than the risk of acquiring Japanese encephalitis, meningococcal invasive
      disease, or rabies. The pre-travel risk assessment of acquiring TBE should
      consider known risk factors which include 1) the country and regions to be
      visited; 2) April to November season; 3) altitude less than 1500 m above the sea
      level; 4) duration of stay; 5) the extent of tick-exposure associated activities
      including leisure and professional outdoor activities within the endemic area;
      and 6) age and comorbidities of the traveler. A major challenge, however, is the
      very low awareness of the risk of contracting TBE in those who travel to
      industrialized European countries.

PMID- 27715428
TI  - Highlight on the dynamic organization of the nucleus.
AB  - The last decade has seen rapid advances in our understanding of the proteins of
      the nuclear envelope, which have multiple roles including positioning the
      nucleus, maintaining its structural organization, and in events ranging from
      mitosis and meiosis to chromatin positioning and gene expression. Diverse new and
      stimulating results relating to nuclear organization and genome function from
      across kingdoms were presented in a session stream entitled "Dynamic Organization
      of the Nucleus" at this year's Society of Experimental Biology (SEB) meeting in
      Brighton, UK (July 2016). This was the first session stream run by the Nuclear
      Dynamics Special Interest Group, which was organized by David Evans, Katja
      Graumann (both Oxford Brookes University, UK) and Iris Meier (Ohio State
      University, USA). The session featured presentations on areas relating to nuclear
      organization across kingdoms including the nuclear envelope, chromatin
      organization, and genome function.

PMID- 27715430
TI  - Letter to the Editor: Sudden death following cranioplasty: vacuum suction to
      blame?

PMID- 27715429
TI  - Integration of tooth morphogenesis and innervation by local tissue interactions,
      signaling networks, and semaphorin 3A.
AB  - The tooth, like many other organs, develops from both epithelial and mesenchymal
      tissues, and has proven to be a valuable tool with which to investigate organ
      formation and peripheral innervation. Tooth formation is regulated by local
      epithelial-mesenchymal tissue interactions, and is closely integrated with
      stereotypic dental nerve navigation and patterning. Recent analyses of the
      function and regulation of semaphorin 3A (SEMA3A) have shed light on the
      regulatory mechanisms that coordinate organogenesis and innervation at the tissue
      and molecular levels. In the tooth, SEM3A acts as a developmentally regulated
      secretory chemo-repellent, that controls tooth innervation during embryonic and
      postnatal development. The tooth germ governs its own innervation by a
      combination of local tissue interactions and SEMA3A expression. SEMA3A signaling,
      in turn, is controlled by a number of conserved signaling effectors, including
      TGF-beta superfamily members, FGF, and WNT; all function in embryo and organ
      development, and are essential for tooth histo-morphogenesis. Thus, SEMA3A driven
      axon guidance is integrated into key odontogenic signaling networks, establishing
      this protein as a critical molecular tether between 2 distinct developmental
      processes (morphogenesis and sensory innervation), both of which are required to
      obtain a functional tooth.

PMID- 27715431
TI  - Letter to the Editor: Seizures and invasive meningiomas.

PMID- 27715432
TI  - Letter to the Editor: Error in the eye of the beholder: crew resource management
      in neurosurgery.

PMID- 27715433
TI  - Factors influencing management of unruptured intracranial aneurysms: an analysis
      of 424 consecutive patients.
AB  - OBJECTIVE The choice between treating and observing unruptured intracranial
      aneurysms is often difficult, with little guidance on which variables should
      influence decision making on a patient-by-patient basis. Here, the authors
      compared demographic variables, aneurysm-related variables, and comorbidities in
      patients who received microsurgical or endovascular treatment and those who were
      conservatively managed to determine which factors push the surgeon toward
      recommending treatment. METHODS A retrospective chart review was conducted of all
      patients diagnosed with an unruptured intracranial aneurysm at their institution
      between January 1, 2013, and January 1, 2016. These patients were dichotomized
      based on whether their aneurysm was treated. Demographic, geographic,
      socioeconomic, comorbidity, and aneurysm-related information was analyzed to
      assess which factors were associated with the decision to treat. RESULTS A total
      of 424 patients were identified, 163 who were treated surgically or
      endovascularly and 261 who were managed conservatively. In a multivariable model,
      an age < 65 years (OR 2.913, 95% CI 1.298-6.541, p = 0.010), a lower Charlson
      Comorbidity Index (OR 1.536, 95% CI 1.274-1.855, p < 0.001), a larger aneurysm
      size (OR 1.176, 95% CI 1.100-1.257, p < 0.001), multiple aneurysms (OR 2.093, 95%
      CI 1.121-3.907, p = 0.020), a white race (OR 2.288, 95% CI 1.245-4.204, p =
      0.008), and living further from the medical center (OR 2.125, 95% CI 1.281-3.522,
      p = 0.003) were all associated with the decision to treat rather than observe.
      CONCLUSIONS Whereas several factors were expected to be considered in the
      decision to treat unruptured intracranial aneurysms, including age, Charlson
      Comorbidity Index, aneurysm size, and multiple aneurysms, other factors such as
      race and proximity to the medical center were unanticipated. Further studies are
      needed to identify such biases in patient treatment and improve treatment
      delineation based on patient-specific aneurysm rupture risk.

PMID- 27715434
TI  - Reverberation index: a novel metric by which to quantify the impact of a
      scientific entity on a given field.
AB  - The authors propose a novel bibilometric index, the reverberation index (r
      index), as a comparative assessment tool for use in determining differential
      reverberation between scientific fields for a given scientific entity.
      Conversely, this may allow comparison of 2 similar scientific entities within a
      single scientific field. This index is calculated using a relatively simple 3
      step process. Briefly, Thompson Reuters' Web of Science is used to produce a
      citation report for a unique search parameter (this may be an author, journal
      article, or topical key word). From this citation report, a list of citing
      journals is retrieved from which a weighted ratio of citation patterns across
      journals can be calculated. This r-index is then used to compare the
      reverberation of the original search parameter across different fields of study
      or wherever a comparison is required. The advantage of this novel tool is its
      ability to transcend a specific component of the scientific process. This affords
      application to a diverse range of entities, including an author, a journal
      article, or a topical key word, for effective comparison of that entity's
      reverberation within a scientific arena. The authors introduce the context for
      and applications of the r-index, emphasizing neurosurgical topics and journals
      for illustration purposes. It should be kept in mind, however, that the r-index
      is readily applicable across all fields of study.

PMID- 27715435
TI  - Quantitative evaluation of vision-related and health-related quality of life
      after endoscopic transsphenoidal surgery for pituitary adenoma.
AB  - OBJECTIVE Endoscopic resection of pituitary adenomas has been reported to improve
      vision function in up to 80%-90% of patients with visual impairment due to these
      adenomas. It is unclear how these reported rates translate into improvement in
      visual outcomes and general health as perceived by the patients. The authors
      evaluated self-assessed health-related quality of life (HR-QOL) and vision
      related QOL (VR-QOL) in patients before and after endoscopic resection of
      pituitary adenomas. METHODS The authors prospectively collected data from 50
      patients who underwent endoscopic resection of pituitary adenomas. This cohort
      included 32 patients (64%) with visual impairment preoperatively. Twenty-seven
      patients (54%) had pituitary dysfunction, including 17 (34%) with hormone
      producing tumors. Patients completed the National Eye Institute Visual
      Functioning Questionnaire and the 36-Item Short Form Health Survey preoperatively
      and 6 weeks and 6 months after surgery. RESULTS Patients with preoperative visual
      impairment reported a significant impact of this condition on VR-QOL
      preoperatively, including general vision, near activities, and peripheral vision;
      they also noted vision-specific impacts on mental health, role difficulties,
      dependency, and driving. After endoscopic resection of adenomas, patients
      reported improvement across all these categories 6 weeks postoperatively, and
      this improvement was maintained by 6 months postoperatively. Patients with
      preoperative pituitary dysfunction, including hormone-producing tumors, perceived
      their general health and physical function as poorer, with some of these patients
      reporting improvement in perceived general health after the endoscopic surgery.
      All patients noted that their ability to work or perform activities of daily
      living was transiently reduced 6 weeks postoperatively, followed by significant
      improvement by 6 months after the surgery. CONCLUSIONS Both VR-QOL and patient's
      perceptions of their ability to do work and perform other daily activities as a
      result of their physical health significantly improved by 6 months after
      endoscopic resection of pituitary adenoma. The use of multidimensional QOL
      questionnaires provides a precise assessment of perceived outcomes after
      endoscopic surgery.

PMID- 27715436
TI  - Midline and off-midline infratentorial supracerebellar approaches to the pineal
      gland.
AB  - OBJECTIVE A common approach to lesions of the pineal region is along the midline
      below the torcula. However, reports of how shifting the approach off midline
      affects the surgical exposure and relationships between the tributaries of the
      vein of Galen are limited. The purpose of this study is to examine the
      microsurgical and endoscopic anatomy of the pineal region as seen through the
      supracerebellar infratentorial approaches, including midline, paramedian,
      lateral, and far-lateral routes. METHODS The quadrigeminal cisterns of 8 formalin
      fixed adult cadaveric heads were dissected and examined with the aid of a
      surgical microscope and straight endoscope. Twenty CT angiograms were examined to
      measure the depth of the pineal gland, slope of the tentorial surface of the
      cerebellum, and angle of approach to the pineal gland in each approach. RESULTS
      The midline supracerebellar route is the shortest and provides direct exposure of
      the pineal gland, although the culmen and inferior and superior vermian
      tributaries of the vein of Galen frequently block this exposure. The off-midline
      routes provide a surgical exposure that, although slightly deeper, may reduce the
      need for venous sacrifice at both the level of the veins from the superior
      cerebellar surface entering the tentorial sinuses and at the level of the
      tributaries of the vein of Galen in the quadrigeminal cistern, and require less
      cerebellar retraction. Shifting from midline to off-midline exposure also
      provides a better view of the cerebellomesencephalic fissure, collicular plate,
      and trochlear nerve than the midline approaches. Endoscopic assistance may aid
      exposure of the pineal gland while preserving the bridging veins. CONCLUSIONS
      Understanding the characteristics of different infratentorial routes to the
      pineal gland will aid in gaining a better view of the pineal gland and
      cerebellomesencephalic fissure and may reduce the need for venous sacrifice at
      the level of the tentorial sinuses draining the upper cerebellar surface and the
      tributaries of the vein of Galen.

PMID- 27715437
TI  - Aggressive resection at the infiltrative margins of glioblastoma facilitated by
      intraoperative fluorescein guidance.
AB  - OBJECTIVE Extent of resection is an important prognostic factor in patients
      undergoing surgery for glioblastoma (GBM). Recent evidence suggests that
      intravenously administered fluorescein sodium associates with tumor tissue,
      facilitating safe maximal resection of GBM. In this study, the authors evaluate
      the safety and utility of intraoperative fluorescein guidance for the prediction
      of histopathological alteration both in the contrast-enhancing (CE) regions,
      where this relationship has been established, and into the non-CE (NCE),
      diffusely infiltrated margins. METHODS Thirty-two patients received fluorescein
      sodium (3 mg/kg) intravenously prior to resection. Fluorescence was
      intraoperatively visualized using a Zeiss Pentero surgical microscope equipped
      with a YELLOW 560 filter. Stereotactically localized biopsy specimens were
      acquired from CE and NCE regions based on preoperative MRI in conjunction with
      neuronavigation. The fluorescence intensity of these specimens was subjectively
      classified in real time with subsequent quantitative image analysis,
      histopathological evaluation of localized biopsy specimens, and radiological
      volumetric assessment of the extent of resection. RESULTS Bright fluorescence was
      observed in all GBMs and localized to the CE regions and portions of the NCE
      margins of the tumors, thus serving as a visual guide during resection. Gross
      total resection (GTR) was achieved in 84% of the patients with an average
      resected volume of 95%, and this rate was higher among patients for whom GTR was
      the surgical goal (GTR achieved in 93.1% of patients, average resected volume of
      99.7%). Intraoperative fluorescein staining correlated with histopathological
      alteration in both CE and NCE regions, with positive predictive values by
      subjective fluorescence evaluation greater than 96% in NCE regions. CONCLUSIONS
      Intraoperative administration of fluorescein provides an easily visualized marker
      for glioma pathology in both CE and NCE regions of GBM. These findings support
      the use of fluorescein as a microsurgical adjunct for guiding GBM resection to
      facilitate safe maximal removal.

PMID- 27715438
TI  - Prediction and detection of seizures from simultaneous thalamic and scalp
      electroencephalography recordings.
AB  - OBJECTIVE The authors explored the feasibility of seizure detection and
      prediction using signals recorded from the anterior thalamic nucleus, a major
      target for deep brain stimulation (DBS) in the treatment of epilepsy. METHODS
      Using data from 5 patients (13 seizures in total), the authors performed a
      feasibility study and analyzed the performance of a seizure prediction and
      detection algorithm applied to simultaneously acquired scalp and thalamic
      electroencephalography (EEG). The thalamic signal was obtained from DBS
      electrodes. The applied algorithm used the similarity index as a nonlinear
      measure for seizure identification, with patient-specific channel and threshold
      selection. Receiver operating characteristic (ROC) curves were calculated using
      data from all patients and channels to compare the performance between DBS and
      EEG recordings. RESULTS Thalamic DBS recordings were associated with a mean
      prediction rate of 84%, detection rate of 97%, and false-alarm rate of 0.79/hr.
      In comparison, scalp EEG recordings were associated with a mean prediction rate
      of 71%, detection rate of 100%, and false-alarm rate of 1.01/hr. From the ROC
      curves, when considering all channels, DBS outperformed EEG for both detection
      and prediction of seizures. CONCLUSIONS This is the first study to compare
      automated seizure detection and prediction from simultaneous thalamic and scalp
      EEG recordings. The authors have demonstrated that signals recorded from DBS
      leads are more robust than EEG recordings and can be used to predict and detect
      seizures. These results indicate feasibility for future designs of closed-loop
      anterior nucleus DBS systems for the treatment of epilepsy.

PMID- 27715439
TI  - Effect of statin treatment on vasospasm-related morbidity and functional outcome
      in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta
      analysis.
AB  - OBJECTIVE The efficacy of statin therapy in treating aneurysmal subarachnoid
      hemorrhage (SAH) remains controversial. In this meta-analysis, the authors
      investigated whether statin treatment significantly reduced the incidence of
      cerebral vasospasm and delayed neurological deficits, promoting a better outcome
      after aneurysmal SAH. METHODS A literature search of the PubMed, Ovid, and
      Cochrane Library databases was performed for randomized controlled trials (RCTs)
      and prospective cohort studies investigating the effect of statin treatment. The
      end points of cerebral vasospasm, delayed ischemic neurological deficit (DIND),
      delayed cerebral infarction, mortality, and favorable outcome were statistically
      analyzed. RESULTS Six RCTs and 2 prospective cohort studies met the eligibility
      criteria, and a total of 1461 patients were included. The meta-analysis
      demonstrated a significant decrease in the incidence of cerebral vasospasm
      (relative risk [RR] 0.76, 95% confidence interval [CI] 0.61-0.96) in patients
      treated with statins after aneurysmal SAH. However, no significant benefit was
      observed for DIND (RR 0.88, 95% CI 0.70-1.12), delayed cerebral infarction (RR
      0.66, 95% CI 0.33-1.31), mortality (RR 0.69, 95% CI 0.39-1.24) or favorable
      outcome, according to assessment by the modified Rankin Scale or Glasgow Outcome
      Scale (RR 0.99, 95% CI 0.92-1.17). CONCLUSIONS Treatment with statins
      significantly decreased the occurrence of vasospasm after aneurysmal SAH. The
      incidence of DIND, delayed cerebral infarction, and mortality were not affected
      by statin treatment. Future research should focus on DIND and how statins
      influence DIND.

PMID- 27715440
TI  - The impact of several craniotomies on transcranial motor evoked potential
      monitoring during neurosurgery.
AB  - OBJECTIVE Transcranial motor evoked potential (tMEP) monitoring is popular in
      neurosurgery; however, the accuracy of tMEP can be impaired by craniotomy. Each
      craniotomy procedure and changes in the CSF levels affects the current spread.
      The aim of this study was to investigate the influence of several craniotomies on
      tMEP monitoring by using C3-4 transcranial electrical stimulation (TES). METHODS
      The authors used the finite element method to visualize the electric field in the
      brain, which was generated by TES, using realistic 3D head models developed from
      T1-weighted MR images. Surfaces of 5 layers of the head (brain, CSF, skull,
      subcutaneous fat, and skin layer) were separated as accurately as possible. The
      authors created 5 models of the head, as follows: normal head; frontotemporal
      craniotomy; parietal craniotomy; temporal craniotomy; and occipital craniotomy.
      The computer simulation was investigated by finite element methods, and clinical
      recordings of the stimulation threshold level of upper-extremity tMEP (UE-tMEP)
      during neurosurgery were also studied in 30 patients to validate the simulation
      study. RESULTS Bone removal during the craniotomy positively affected the
      generation of the electric field in the motor cortex if the motor cortex was just
      under the bone at the margin of the craniotomy window. This finding from the
      authors' simulation study was consistent with clinical reports of frontotemporal
      craniotomy cases. A major decrease in CSF levels during an operation had a
      significantly negative impact on the electric field when the motor cortex was
      exposed to air. The CSF surface level during neurosurgery depends on the body
      position and location of the craniotomy. The parietal craniotomy and temporal
      craniotomy were susceptible to the effect of the changing CSF level, based on the
      simulation study. A marked increase in the threshold following a decrease in CSF
      was actually recorded in clinical reports of the UE-tMEP threshold from a
      temporal craniotomy. However, most frontotemporal craniotomy cases were minimally
      affected by a small decrease in CSF. CONCLUSIONS Bone removal during a craniotomy
      positively affects the generation of the electric field in the motor cortex if
      the motor cortex is just under the bone at the margin of the craniotomy window.
      The CSF decrease and the shifting brain can negatively affect tMEP ignition.
      These changes should be minimized to maintain the original conductivity between
      the motor cortex and the skull, and the operation team must remember the
      fluctuation of the tMEP threshold.

PMID- 27715442
TI  - Tunneling nanotubes: A possible highway in the spreading of tau and other prion
      like proteins in neurodegenerative diseases.
AB  - The mechanisms of intercellular spreading of amyloidogenic proteins involved in
      neurodegenerative diseases have yet to be fully elucidated. While secretion has
      been implicated in the transfer of many proteins, including prions and alpha
      synuclein, tunneling nanotubes (TNTs) have also been demonstrated for prions and
      mutant Huntingtin. Here, we provide further evidence that Tau aggregates, which
      have been demonstrated to predominantly be transferred via secretion, can also be
      found in TNTs. Additionally, cells that have taken up Tau have increased TNT
      formation. Coupled with previous evidence that other amyloidogenic aggregates
      also induce TNT formation we propose that misfolded protein aggregates can,
      through a common mechanism, promote the formation of TNTs and thereby their own
      intercellular transfer, contributing to the propagation of pathology.

PMID- 27715441
TI  - Specific genomic cues regulate Cajal body assembly.
AB  - The assembly of specialized sub-nuclear microenvironments known as nuclear bodies
      (NBs) is important for promoting efficient nuclear function. In particular, the
      Cajal body (CB), a prominent NB that facilitates spliceosomal snRNP biogenesis,
      assembles in response to genomic cues. Here, we detail the factors that regulate
      CB assembly and structural maintenance. These include the importance of
      transcription at nucleating gene loci, the grouping of these genes on human
      chromosomes 1, 6 and 17, as well as cell cycle and biochemical regulation of CB
      protein function. We also speculate on the correlation between CB formation and
      RNA splicing levels in neurons and cancer. The timing and location of these
      specific molecular events is critical to CB assembly and its contribution to
      genome function. However, further work is required to explore the emerging
      biophysical characteristics of CB assembly and the impact upon subsequent genome
      reorganization.

PMID- 27715447
TI  - Recombinant fungal entomopathogen RNAi target insect gene.
AB  - RNA interference (RNAi) technology is considered as an alternative for control of
      pests. However, RNAi has not been used in field conditions yet, since delivering
      exogenous ds/siRNA to target pests is very difficult. The laboratory methods of
      introducing the ds/siRNA into insects through feeding, micro feeding / dripping
      and injecting cannot be used in fields. Transgenic crop is perhaps the most
      effective application of RNAi for pest control, but it needs long-time basic
      researches in order to reduce the cost and evaluate the safety. Therefore,
      transgenic microbe is maybe a better choice. Entomopathogenic fungi generally
      invade the host insects through cuticle like chemical insecticides contact insect
      to control sucking sap pests. Isaria fumosorosea is a common fungal
      entomopathogen in whitefly, Bemisia tabaci. We constructed a recombinant strain
      of I. fumosorosea expressing specific dsRNA of whitefly's TLR7 gene. It could
      silence the TLR7 gene and improve the virulence against whitefly. Transgenic
      fungal entomopathogen has shown great potential to attain the application of RNAi
      technology for pests control in fields. In the future, the research interests
      should be focused on the selection of susceptible target pests and their vital
      genes, and optimizing the methods for screening genes and recombinants as well.

PMID- 27715446
TI  - Chemotactic G protein-coupled receptors control cell migration by repressing
      autophagosome biogenesis.
AB  - Chemotactic migration is a fundamental behavior of cells and its regulation is
      particularly relevant in physiological processes such as organogenesis and
      angiogenesis, as well as in pathological processes such as tumor metastasis. The
      majority of chemotactic stimuli activate cell surface receptors that belong to
      the G protein-coupled receptor (GPCR) superfamily. Although the autophagy
      machinery has been shown to play a role in cell migration, its mode of regulation
      by chemotactic GPCRs remains largely unexplored. We found that ligand-induced
      activation of 2 chemotactic GPCRs, the chemokine receptor CXCR4 and the urotensin
      2 receptor UTS2R, triggers a marked reduction in the biogenesis of
      autophagosomes, in both HEK-293 and U87 glioblastoma cells. Chemotactic GPCRs
      exert their anti-autophagic effects through the activation of CAPNs, which
      prevent the formation of pre-autophagosomal vesicles from the plasma membrane. We
      further demonstrated that CXCR4- or UTS2R-induced inhibition of autophagy favors
      the formation of adhesion complexes to the extracellular matrix and is required
      for chemotactic migration. Altogether, our data reveal a new link between GPCR
      signaling and the autophagy machinery, and may help to envisage therapeutic
      strategies in pathological processes such as cancer cell invasion.

PMID- 27715443
TI  - Emerging connections between RNA and autophagy.
AB  - Macroautophagy/autophagy is a key catabolic process, essential for maintaining
      cellular homeostasis and survival through the removal and recycling of unwanted
      cellular material. Emerging evidence has revealed intricate connections between
      the RNA and autophagy research fields. While a majority of studies have focused
      on protein, lipid and carbohydrate catabolism via autophagy, accumulating data
      supports the view that several types of RNA and associated ribonucleoprotein
      complexes are specifically recruited to phagophores (precursors to
      autophagosomes) and subsequently degraded in the lysosome/vacuole. Moreover,
      recent studies have revealed a substantial number of novel autophagy regulators
      with RNA-related functions, indicating roles for RNA and associated proteins not
      only as cargo, but also as regulators of this process. In this review, we discuss
      widespread evidence of RNA catabolism via autophagy in yeast, plants and animals,
      reviewing the molecular mechanisms and biological importance in normal
      physiology, stress and disease. In addition, we explore emerging evidence of core
      autophagy regulation mediated by RNA-binding proteins and noncoding RNAs, and
      point to gaps in our current knowledge of the connection between RNA and
      autophagy. Finally, we discuss the pathological implications of RNA-protein
      aggregation, primarily in the context of neurodegenerative disease.

PMID- 27715450
TI  - More wrinkles to Bt susceptibility.

PMID- 27715448
TI  - Membrane orientation dynamics of lipid-modified small GTPases.
AB  - Lipid-modified GTPases in the Ras superfamily that mediate a variety of cell
      signaling processes were thought to be passively anchored to membranes. However,
      an increasing number of recent studies are finding that membrane binding of these
      proteins is hardly a passive process, and it involves the soluble catalytic
      domain as well as the lipid anchor. The catalytic domain adopts multiple
      orientations on the membrane surface due to internal fluctuations that are
      modulated by activation status and mutations. Distinct orientation preferences
      among small GTPases likely lead to differential signaling outcomes, as downstream
      effectors can sense different orientations. We review recent studies behind this
      important conclusion.

PMID- 27715449
TI  - Cdc42 in actin dynamics: An ordered pathway governed by complex equilibria and
      directional effector handover.
AB  - The small GTPase, Cdc42, is a key regulator of actin dynamics, functioning to
      connect multiple signals to actin polymerization through effector proteins of the
      Wiskott-Aldrich syndrome protein (WASP) and Transducer of Cdc42-dependent actin
      assembly (TOCA) families. WASP family members serve to couple Cdc42 with the
      actin nucleator, the Arp2/3 complex, via direct interactions. The regulation of
      these proteins in the context of actin dynamics has been extensively studied.
      Studies on the TOCA family, however, are more limited and relatively little is
      known about their roles and regulation. In this commentary we highlight new
      structural and biophysical insight into the involvement of TOCA proteins in the
      pathway of Cdc42-dependent actin dynamics. We discuss the biological implications
      of the low affinity interactions between the TOCA family and Cdc42, as well as
      probing the sequential binding of TOCA1 and the WASP homolog, N-WASP, to Cdc42.
      We place our current research in the context of the wealth of biophysical,
      structural and functional data from earlier studies pertaining to the Cdc42/N
      WASP/Arp2/3 pathway of actin polymerization. Finally, we describe the molecular
      basis for a sequential G protein-effector handover from TOCA1 to N-WASP.

PMID- 27715452
TI  - Cabozantinib inhibits tumor growth and metastasis of a patient-derived xenograft
      model of papillary renal cell carcinoma with MET mutation.
AB  - MET plays an important role in the development and progression of papillary renal
      cell carcinoma (pRCC). Evaluation of efficacy of MET inhibitors against pRCC has
      been hampered by limited preclinical models depicting MET abnormalities. We
      established a new patient-derived xenograft (PDX) model of pRCC carrying an
      activating mutation of MET and tested the ability of cabozantinib, an inhibitor
      of receptor tyrosine kinases including MET, to inhibit tumor growth and
      metastasis. Precision-cut, thin tissue slices from a pRCC specimen obtained by
      nephrectomy were implanted under the renal capsule of RAG2-/-gammaC-/- mice to
      establish first generation TSG-RCC-030. Histologic and genetic fidelity and
      metastatic potential of this model were characterized by immunohistochemistry,
      direct DNA sequencing and quantitative polymerase chain reaction (qPCR). The
      effect of cabozantinib on tumor growth and metastasis was evaluated. Whether
      measurements of circulating tumor DNA (ctDNA) by allele-specific qPCR could be
      used as a biomarker of tumor growth and response to therapy was determined.
      Subrenal and subcutaneous tumor grafts showed high take rates and metastasized to
      the lung. Both primary tumors and metastases expressed typical markers of pRCC
      and carried the same activating MET mutation as the parental tumor. Cabozantinib
      treatment caused striking tumor regression and inhibited lung metastasis in TSG
      RCC-030. Plasma ctDNA levels correlated with tumor volume in control mice and
      changed in response to cabozantinib treatment. TSG-RCC-030 provides a realistic
      preclinical model to better understand the development and progression of pRCC
      with MET mutation and accelerate the development of new therapies for pRCC.

PMID- 27715454
TI  - Diverse profiles of N-acyl-homoserine lactones in biofilm forming strains of
      Cronobacter sakazakii.
AB  - The present study investigates the role of quorum sensing (QS) molecules
      expressed by C. sakazakii in biofilm formation and extracellular polysaccharide
      expression. The QS signaling was detected using Chromobacterium violaceum 026 and
      Agrobacterium tumefaciens NTL4(pZLR4) based bioassay. Long chain N-acyl
      homoserine lactones (AHLs) with C6- C18 chain length were identified using High
      Performance Liquid Chromatography and Liquid Chromatography-High Resolution Mass
      Spectrometry. A higher Specific Biofilm Formation (SBF) index (p < 0.05) with the
      presence of genes associated with cellulose biosynthesis (bcsA, bcsC and bcsG)
      was observed in the strains. AHLs and their mechanisms can serve as novel targets
      for developing technologies to eradicate and prevent biofilm formation by C.
      sakazakii.

PMID- 27715451
TI  - Assembly and trafficking of box C/D and H/ACA snoRNPs.
AB  - Box C/D and box H/ACA snoRNAs are abundant non-coding RNAs that localize in the
      nucleolus and mostly function as guides for nucleotide modifications. While a
      large pool of snoRNAs modifies rRNAs, an increasing number of snoRNAs could also
      potentially target mRNAs. ScaRNAs belong to a family of specific RNAs that
      localize in Cajal bodies and that are structurally similar to snoRNAs. Most
      scaRNAs are involved in snRNA modification, while telomerase RNA, which contains
      H/ACA motifs, functions in telomeric DNA synthesis. In this review, we describe
      how box C/D and H/ACA snoRNAs are processed and assembled with core proteins to
      form functional RNP particles. Their biogenesis involve several transport factors
      that first direct pre-snoRNPs to Cajal bodies, where some processing steps are
      believed to take place, and then to nucleoli. Assembly of core proteins involves
      the HSP90/R2TP chaperone-cochaperone system for both box C/D and H/ACA RNAs, but
      also several factors specific for each family. These assembly factors chaperone
      unassembled core proteins, regulate the formation and disassembly of pre-snoRNP
      intermediates, and control the activity of immature particles. The AAA+ ATPase
      RUVBL1 and RUVBL2 belong to the R2TP co-chaperones and play essential roles in
      snoRNP biogenesis, as well as in the formation of other macro-molecular
      complexes. Despite intensive research, their mechanisms of action are still
      incompletely understood.

PMID- 27715453
TI  - Leukocyte transendothelial migration: A local affair.
AB  - Inflammation is part of the complex biological response of body tissues to
      harmful stimuli, such as pathogens. It serves as a protective response that
      involves leukocytes, blood vessels and molecular mediators with the purpose to
      eliminate the initial cause of cell injury and to initiate tissue repair.
      Inflammation is tightly regulated by the body and is associated with transient
      crossing of leukocytes through the blood vessel wall, a process called
      transendothelial migration (TEM) or diapedesis. TEM is a close collaboration
      between leukocytes on one hand and the endothelium on the other. Limiting
      vascular leakage during TEM but also when the leukocyte has crossed the
      endothelium is essential for maintaining vascular homeostasis. Although many
      details have been uncovered during the recent years, the molecular mechanisms
      from the vascular part that drive TEM still shows significant gaps in our
      understanding. This review will focus on the local signals that are induced in
      the endothelium that regulate leukocyte TEM and simultaneous preservation of
      endothelial barrier function.

PMID- 27715455
TI  - Assessment of geriatric syndromes and physical function in people living with
      HIV.
AB  - As the number of older adults living with HIV continues to increase,
      understanding how to incorporate geriatric assessments within HIV care will be
      critical. Assessment of geriatric syndromes and physical function can be useful
      tools for HIV clinicians and researchers to help identify the most vulnerable
      older adults and to better understand the aging process in people living with HIV
      (PLWH). This review focuses on the assessment of falls, frailty, and physical
      function, first in the general population of older adults, and includes a
      specific focus on use of these assessments in older adults living with HIV.

PMID- 27715456
TI  - Sequence Based Structural Characterization and Genetic Diversity Analysis of Full
      Length TLR4 CDS in Crossbred and Indigenous Cattle.
AB  - The exploration of candidate genes for immune response in cattle may be vital for
      improving our understanding regarding the species specific response to pathogens.
      Toll-like receptor 4 (TLR4) is mostly involved in protection against the
      deleterious effects of Gram negative pathogens. Approximately 2.6 kb long cDNA
      sequence of TLR4 gene covering the entire coding region was characterized in two
      Indian milk cattle (Vrindavani and Tharparkar). The phylogenetic analysis
      confirmed that the bovine TLR4 was apparently evolved from an ancestral form that
      predated the appearance of vertebrates, and it is grouped with buffalo, yak, and
      mithun TLR4s. Sequence analysis revealed a 2526-nucleotide long open reading
      frame (ORF) encoding 841 amino acids, similar to other cattle breeds. The
      calculated molecular weight of the translated ORF was 96144 and 96040.9 Da; the
      isoelectric point was 6.35 and 6.42 in Vrindavani and Tharparkar cattle,
      respectively. The Simple Modular Architecture Research Tool (SMART) analysis
      identified 14 leucine rich repeats (LRR) motifs in bovine TLR4 protein. The
      deduced TLR4 amino acid sequence of Tharparkar had 4 different substitutions as
      compared to Bos taurus, Sahiwal, and Vrindavani. The signal peptide cleavage site
      predicted to lie between 16th and 17th amino acid of mature peptide. The
      transmebrane helix was identified between 635-657 amino acids in the mature
      peptide.

PMID- 27715457
TI  - Archaeal RNA ligase from thermoccocus kodakarensis for template dependent
      ligation.
AB  - Nicking-sealing RNA ligases play a significant biological role in host defense
      and cellular repair, and have become an important molecular tool in biomedical
      engineering. Due to the propensity for RNA to form secondary structures, RNA
      modifying enzymes with elevated optimum temperatures are highly desired. Current
      characterized double stranded RNA ligases, such as the bacteriophage T4 RNA
      ligase 2, while possessing good template dependency, are not active at elevated
      temperatures. The few characterized RNA ligases from thermophiles exhibit high
      template independency. We synthesize and characterize here, KOD RNA ligase
      (KOD1Rnl), a thermostable and template dependent RNA ligase from the archaeon,
      Thermoccocus Kodakarensis. We disclose that a 13 time reduction in template
      independent ligation can be achieved with the addition of a single stranded
      DNase, such as RecJ. We also elucidate the effects of the presence of blood
      proteins on the activity of KOD1Rnl. Template dependent and thermostable RNA
      ligases, such as KOD RNA ligase, can be utilized in RNA detection, modification
      and sequencing.

PMID- 27715458
TI  - Alternative splicing of a viral mirtron differentially affects the expression of
      other microRNAs from its cluster and of the host transcript.
AB  - Interplay between alternative splicing and the Microprocessor may have
      differential effects on the expression of intronic miRNAs organized into
      clusters. We used a viral model - the LAT long non-coding RNA (LAT lncRNA) of
      Marek's disease oncogenic herpesvirus (MDV-1), which has the mdv1-miR-M8-M6-M7
      M10 cluster embedded in its first intron - to assess the impact of splicing
      modifications on the biogenesis of each of the miRNAs from the cluster. Drosha
      silencing and alternative splicing of an extended exon 2 of the LAT lncRNA from a
      newly identified 3' splice site (SS) at the end of the second miRNA of the
      cluster showed that mdv1-miR-M6 was a 5'-tailed mirtron. We have thus identified
      the first 5'-tailed mirtron within a cluster of miRNAs for which alternative
      splicing is directly associated with differential expression of the other miRNAs
      of the cluster, with an increase in intronic mdv1-miR-M8 expression and a
      decrease in expression of the exonic mdv1-miR-M7, and indirectly associated with
      regulation of the host transcript. According to the alternative 3SS used for the
      host intron splicing, the mdv1-miR-M6 is processed as a mirtron by the
      spliceosome, dispatching the other miRNAs of the cluster into intron and exon, or
      as a canonical miRNA by the Microprocessor complex. The viral mdv1-miR-M6 mirtron
      is the first mirtron described that can also follow the canonical pathway.

PMID- 27715459
TI  - Modelling anaerobic digestion in an industrial biogas digester: Application of
      lactate-including ADM1 model (Part II).
AB  - A modified Anaerobic Digestion Model No. 1 (ADM1xp) including lactate was applied
      to a full-scale biogas plant. This model considers monosaccharides to degrade
      through lactic acid, which further degrades majorly into acetate followed by
      propionate and butyrate. Experimental data were derived from the previous works
      in the same laboratory, and the proposed parameters were validated against batch
      experiments. After successful validation, the biogas plant bearing a fermenter
      size of 7 dam3 and operated with food waste and cattle manure was simulated. The
      biogas production and methane content were reliably simulated, and a good fit
      could be obtained against the experimental data with an average difference of
      less than 1%. When compared to the original ADM1 model, the performance of the
      lactate-incorporated model was found to be improved. Inclusion of lactate as a
      parameter in the ADM1xp model is recommended for an increased sensitivity and
      enhanced prediction principally for systems dealing with high carbohydrate and
      lactate loads.

PMID- 27715460
TI  - Bovine Sex Determining Region Y: Cloning, Optimized Expression, and Purification.
AB  - Sex determining region Y gene (SRY) is located on Y chromosome and encodes a
      protein with 229 amino acids. In this study, ORF region of SRY with a length of
      690 bp was synthesized using PCR and ligated to pET28a (+), then transformed in
      E.coli DH5alpha. E.coli BL21 (DE3) strain was chosen to express recombinant
      bovine SRY protein. A set of optimization steps was taken including different
      concentrations of IPTG, glucose, and temperatures at differed incubation times
      after the induction. Results showed that temperature points and different
      concentrations of IPTG and glucose had a significant effect (p < 0.01) on total
      protein and recombinant bovine SRY. After purification, various temperatures and
      concentrations of IPTG showed meaningful effects (p < 0.01) on the solubility of
      expressed recombinant SRY. Highest soluble rSRY protein amount was achieved where
      0.5 mM IPTG and 0.5% glucose was used at 20 degrees C during induction. In the
      absence of glucose, the highest amount of soluble recombinant SRY levels were
      achieved at the concentrations of 0.8 mM of IPTG at 28 degrees C, 20 degrees C,
      and 1.5 mM IPTG at 37 degrees C during induction for 16, 24, and 8 hours,
      respectively. Regarding the results obtained in this study, it could be stated
      that by decreasing temperature and inducer concentration, soluble bovine SRY
      protein expression increases.

PMID- 27715461
TI  - Correlation of the A-FABP Gene Polymorphism and mRNA Expression with
      Intramuscular Fat Content in Three-Yellow Chicken and Hetian-Black Chicken.
AB  - The adipocyte-type fatty acid-binding protein (A-FABP) is considered a candidate
      gene for fat metabolism; thus, it affects fat deposition in chickens. The present
      study was designed to examine the polymorphism and mRNA abundance of the A-FABP
      gene with intramuscular fat (IMF) in the pectoralis muscles (PM) and leg muscles
      (LM) of Three-yellow Chicken (TYC) and Hetian-black Chicken (HTBC). In total, 60
      TYCs and 60 HTBCs were sacrificed using exsanguination at market age. The IMF
      contents of the PM and LM in the HTBC were significantly higher than those in the
      TYC. Three genotypes of the A-FABP gene first exon, AA, AB, and BB, were examined
      by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP),
      and a C51 T mutational site, which is a silent substitution mutation, was
      revealed. The IMF contents of the AA genotype in the PM of the HTBC were
      significantly higher than those in the AB genotype; thus, the C51 T mutable site
      is a gene marker for selecting a higher IMF content in the PM of the HTBC. The
      relative expression of the A-FABP mRNA in the LM of the HTBC, which was measured
      by quantitative real-time PCR, was significantly higher than in the TYC. A
      significantly positive association was detected between A-FABP expression with
      the IMF contents of the PM and LM of both the TYC and the HTBC. These results
      provide basic data that might be helpful to further research the role of the A
      FABP gene in fat deposition and fatty acid metabolism in chickens.

PMID- 27715463
TI  - Groundwater quality in alluvial and prolluvial areas under the influence of
      irrigated agriculture activities.
AB  - The aim of this study was to investigate the groundwater pollution from alluvial
      aquifers lying under surface agriculture activities in two geologically different
      areas: alluvial and prolluvial. The groundwater in investigated areas is neutral
      to alkaline (pH 7.05-8.45), and the major dissolved ions are bicarbonate and
      calcium. Groundwater samples from the alluvial area are characterized by nitrate
      concentration above the national maximum concentration limit (MCL) at 20.5% of
      samples [mean value (Me) 6.31 mg/L], arsenic concentrations greater than national
      MCL at 35.6% of investigated samples (Me 12.12 ug/L) and elevated concentrations
      of iron (Me 202.37 ug/L) and manganese (Me 355.22 ug/L) at 22.7% and 81% of
      investigated samples, respectively. Groundwater samples from the prolluvial area
      did not show significantly elevated concentrations of heavy metals, but the
      concentration of nitrate was considerably higher (Me 65.06 mg/L). Factor analysis
      positively correlates As with Mn and Fe, suggesting its natural origin. Nitrate
      was found in positive correlation with SO42- and Ni but in negative with NH4+,
      suggesting its anthropogenic origin and the relationship of these ions in the
      process of denitrification. The t-test analysis showed a significant difference
      between nitrate pollution of groundwater from alluvial and prolluvial areas.
      According to the chemical composition of groundwater, the process of
      denitrification is considered to be the main reason for the reduced presence of
      nitrate in the groundwater lying under alluvial deposits represented by chalk and
      sandstones. Denitrification in groundwater lying under prolluvial deposits
      represented by magmatic and metamorphic rock formations was not observed.

PMID- 27715462
TI  - Capsaicin reactivates hMOF in gastric cancer cells and induces cell growth
      inhibition.
AB  - Capsaicin (CAP) is the major pungent component of chili pepper and is being
      evaluated for use against numerous types of tumors. Although CAP is indicated to
      target multiple signaling pathways, exact mechanisms of how it disturb cancer
      cell metablism remain obscure. Recent studies revealed Sirtuin 1 (SIRT1) serves
      as a potential target of CAP in cancer cells, indicating a direct regulation of
      cancer cell histone acetylation by capsaicin. The present study evaluated the
      effect of CAP on gastric cancer (GC) cell lines to understand the mechanism of
      cell growth inhibition. The results showed that CAP could significantly suppress
      cell growth, while altering histone acetylation in GC cell lines. Further studies
      found that hMOF, a major histone acetyltranferase for H4K16, is central to CAP
      induced epigenetic changes. Reduced hMOF activity was detected in GC tissues,
      which could be restored by CAP both in vivo and in vitro. These findings revealed
      an important role of hMOF-mediated histone acetylation in CAP-directed anti
      cancer processes, and suggested CAP as a potential drug for use in gastric cancer
      prevention and therapy.

PMID- 27715464
TI  - Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor
      angiogenesis after chemotherapy as visualized by real-time FUCCI imaging.
AB  - We previously demonstrated that quiescent cancer cells in a tumor are resistant
      to conventional chemotherapy as visualized with a fluorescence ubiquitination
      cell cycle indicator (FUCCI). We also showed that proliferating cancer cells
      exist in a tumor only near nascent vessels or on the tumor surface as visualized
      with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the
      present study, we show the relationship between cell-cycle phase and chemotherapy
      induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell
      cycle and nestin-driven GFP to detect nascent blood vessels. We observed that
      chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after
      treatment, had much more and deeper tumor vessels than untreated tumors. These
      newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast,
      formerly quiescent cancer cells decoyed to S/G2 phase by a telomerase-dependent
      adenovirus did not induce tumor angiogenesis. The present results further
      demonstrate the importance of the cancer-cell position in the cell cycle in order
      that chemotherapy be effective and not have the opposite effect of stimulating
      tumor angiogenesis and progression.

PMID- 27715465
TI  - Comparison of Cryopreservation Protocols (Single and Two-steps) and Thawing (Fast
      and Slow) for Canine Sperm.
AB  - In addition to the existence of several cryopreservation protocols, no systematic
      research has been carried out in order to confirm the suitable protocol for
      canine sperm. This study aims to assess the effect of adding 5% glycerol during
      cryopreservation at 37 degrees C (one-step) and 5 degrees C (two-steps), in
      addition of testing two thawing protocols (37 degrees C for 30 seconds, and 70
      degrees C for 8 seconds). We used 12 sperm samples divided into four experimental
      groups: Single-Step - Slow Thawing Group; Two-Step - Slow Thawing Group; Single
      Step - Fast Thawing Group; and Two-Step - Fast Thawing Group. Frozen-thawed
      samples were submitted to automated analysis of sperm motility, evaluation of
      plasmatic membrane integrity, acrosomal integrity, mitochondrial activity, sperm
      morphology, sperm susceptibility to oxidative stress, and sperm binding assay to
      perivitellinic membrane of chicken egg yolk. Considering the comparison between
      freezing protocols, no statistical differences were verified for any of the
      response variables. When comparison between thawing protocols was performed, slow
      thawing protocol presented higher sperm count bound to perivitelline membrane of
      chicken egg yolk, compared to fast thawing protocol. Regardless of the freezing
      process, the slow thawing protocol can be recommended for the large scale
      cryopreservation of canine semen, since it shows a consistent better functional
      result.

PMID- 27715467
TI  - Molecular identification and nanoremediation of microbial contaminants in algal
      systems using untreated wastewater.
AB  - Wastewater-algal biomass is a promising option to biofuel production. However,
      microbial contaminants constitute a substantial barrier to algal biofuel yield. A
      series of algal strains, Nannochloris oculata and Chlorella vulgaris samples (n =
      30), were purchased from the University of Texas, and were used for both stock
      flask cultures and flat-panel vertical bioreactors. A number of media were used
      for isolation and differentiation of potential contaminants according to
      laboratory standards (CLSI). Conventional PCR amplification was performed
      followed by 16S rDNA sequencing to identify isolates at the species level.
      Nanotherapeutics involving a nanomicellar combination of natural chitosan and
      zinc oxide (CZNPs) were tested against the microbial lytic groups through Minimum
      Inhibitory Concentration (MIC) tests and Transmission Electronic Microscopy
      (TEM). Results indicated the presence of Pseudomonas spp., Bacillus pumilus/
      safensis, Cellulosimicrobium cellulans, Micrococcus luteus and Staphylococcus
      epidermidis strains at a substantial level in the wastewater-fed algal reactors.
      TEM confirmed the effectiveness of CZNPs on the lytic group while the average
      MICs (mg/mL) detected for the strains, Pseudomonas spp, Micrococcus luteus, and
      Bacillus pumilus were 0.417, 3.33, and 1.458, respectively. Conclusively, CZNP
      antimicrobials proved to be effective as inhibitory agents against currently
      identified lytic microbial group, did not impact algae cells, and shows promise
      for in situ interventions.

PMID- 27715469
TI  - SOTIO.

PMID- 27715466
TI  - Monoclonal antibodies protect from Staphylococcal Enterotoxin K (SEK) induced
      toxic shock and sepsis by USA300 Staphylococcus aureus.
AB  - Staphylococcus aureus is a leading infectious cause of life-threatening disease
      in humans, yet there is currently no vaccine to combat this bacterium. The
      pathogenesis of S. aureus is mediated by a diverse array of protein toxins
      including a large family of secreted pyrogenic superantigens. Neutralization of
      superantigens, including SEB and TSST-1, has proven to be protective in several
      animal models of toxic shock and sepsis. We demonstrate, for the first time, that
      a far more prevalent staphylococcal superantigen, SEK, can also induce lethal
      shock in mice. Additionally, we describe monoclonal antibodies (mAbs) that
      inhibit SEK-induced mitogenicity as well as protect against SEK-induced
      lethality, and enhance survival from S. aureus septicemia in murine models. MAb
      4G3 (IgG2b), mAb-5G2 (IgG1), and mAb-9H2 (IgG1), all inhibit SEK-induced
      proliferation and cytokine production of human immune cells. We then demonstrate
      that passive immunization with a combination of mAb-4G3 and mAb-5G4, 2 mAbs that
      do not compete for epitope(s) on SEK, significantly enhance survival in a murine
      model of SEK-induced toxic shock (p = 0.006). In the setting of sepsis, passive
      immunization with this combination of mAbs also significantly enhances survival
      in mice after challenge with CA-MRSA strain USA300 (p = 0.03). Furthermore,
      septic mice that received mAb treatment in conjunction with vancomycin exhibit
      less morbidity than mice treated with vancomycin alone. Taken together, these
      findings suggest that the contribution of SEK to S. aureus pathogenesis may be
      greater than previously appreciated, and that adjunctive therapy with passive
      immunotherapy against SEs may be beneficial.

PMID- 27715470
TI  - Improvement of lincomycin production by mutant selection and metabolic
      regulation.
AB  - Lincomycin is a lincosamide antibiotic produced by Streptomyces lincolnensis.
      Through mutagenesis by ethylmethansulfonate (EMS) and ultraviolet (UV)
      irradiation repeatedly, M2 was picked out in plate with glutamine and
      propylproline orderly. In 50-L stirred bioreactor, the production of lincomycin,
      fermented by M2, was increased to 8136 u/ml under the optimal condition as
      compared to original strain S. lincolnensis 07-5 (6634 u/ml). Two-dimensional gel
      electrophoresis (2-D GE) and mass spectrometry (MS)-shown LmbG, LmbI, and
      acetohydroxy acid isomeroreductase were remarkably synthesized in M2. The gene
      lmbG and lmbI are responsible for methylation in the lincomycin biosynthetic
      cluster, while acetohydroxy acid isomeroreductase contributes to stronger
      metabolic capability. Finally, we obtained a better strain for industrial
      production.

PMID- 27715471
TI  - The contribution of capsule polysaccharide genes to virulence of Klebsiella
      pneumoniae.

PMID- 27715472
TI  - A novel process for the production of high-purity galactooligosaccharides (GOS)
      using consortium of microbes.
AB  - Galactooligosaccharides (GOS) are nondigestible dietary fibers which have a
      beneficial effect on human health by promoting the growth of probiotic bacteria
      in the gut. In addition, other health benefits have been reported from
      oligosaccharides consumption such as stimulation of intestinal mobility, colon
      cancer prevention, mineral absorption as well as protection against certain
      pathogenic bacterial infections. The goal of this research was to develop an
      efficient biotransformation system using a consortium of microbes for the
      production of >=85% pure GOS and reusing the cell biomass in repeated cycles of
      biotransformation. Production of GOS by lactose transgalactosylation using whole
      cells of Sporobolomyces singularis MTCC 5491 as a source of beta-galactosidase
      and monosaccharides utilization by yeast isolate (NUTIDY007) were studied. For
      increasing the purity of GOS, growth and bioconversion parameters on the
      transgalactosylation by the whole cells were investigated. Further, continuous
      production of GOS was studied in a reactor with microfiltration membrane system.
      A maximum GOS purity of 42% was achieved using single culture of S. singularis.
      Under optimized conditions, single culture of S. singularis produced a maximum of
      56% pure GOS. Addition of second culture to the reaction mixture for utilization
      of glucose significantly increased the GOS purity from 56% to >=85%. The product
      consisted of tri- to penta-galactooligosaccharides. Trisaccharides were the main
      component of the reaction mixture. A maximum productivity of 10.9 g/L/hr was
      obtained under the optimum conditions.

PMID- 27715473
TI  - Evaluating the effectiveness of air quality regulations: A review of
      accountability studies and frameworks.
AB  - : Assessments of past environmental policies-termed accountability studies
      contribute important information to the decision-making process used to review
      the efficacy of past policies, and subsequently aid in the development of
      effective new policies. These studies have used a variety of methods that have
      achieved varying levels of success at linking improvements in air quality and/or
      health to regulations. The Health Effects Institute defines the air pollution
      accountability framework as a chain of events that includes the regulation of
      interest, air quality, exposure/dose, and health outcomes, and suggests that
      accountability research should address impacts for each of these linkages. Early
      accountability studies investigated short-term, local regulatory actions (for
      example, coal use banned city-wide on a specific date or traffic pattern changes
      made for Olympic Games). Recent studies assessed regulations implemented over
      longer time and larger spatial scales. Studies on broader scales require
      accountability research methods that account for effects of confounding factors
      that increase over time and space. Improved estimates of appropriate baseline
      levels (sometimes termed "counterfactual"-the expected state in a scenario
      without an intervention) that account for confounders and uncertainties at each
      link in the accountability chain will help estimate causality with greater
      certainty. In the direct accountability framework, researchers link outcomes with
      regulations using statistical methods that bypass the link-by-link approach of
      classical accountability. Direct accountability results and methods complement
      the classical approach. New studies should take advantage of advanced planning
      for accountability studies, new data sources (such as satellite measurements),
      and new statistical methods. Evaluation of new methods and data sources is
      necessary to improve investigations of long-term regulations, and associated
      uncertainty should be accounted for at each link to provide a confidence estimate
      of air quality regulation effectiveness. The final step in any accountability is
      the comparison of results with the proposed benefits of an air quality policy.
      IMPLICATIONS: The field of air pollution accountability continues to grow in
      importance to a number of stakeholders. Two frameworks, the classical
      accountability chain and direct accountability, have been used to estimate
      impacts of regulatory actions, and both require careful attention to confounders
      and uncertainties. Researchers should continue to develop and evaluate both
      methods as they investigate current and future air pollution regulations.

PMID- 27715474
TI  - Reply to Varghese et al.'s response to Wu et al. - "Cost effectiveness analysis
      of infant pneumococcal vaccination in Malaysia and Hong Kong".

PMID- 27715475
TI  - Learning to eat again: Intuitive eating practices among retired female collegiate
      athletes.
AB  - The present study used an open-ended survey to collect information about current
      eating practices and coping strategies among 218 retired female athletes. An
      inductive and deductive thematic analysis revealed three themes relevant to the
      intuitive eating framework-permission to eat; recognizing internal hunger and
      satiety cues; and eating to meet physical and nutritional needs. Athletes
      described feeling liberated with regards to their eating following retirement
      from sport, and for some this included an alleviation of disordered eating
      practices. These changes, however, required an effortful process of
      recalibration, during which athletes had to relearn and reinterpret their body's
      physiological signals of hunger and satiety. Additional research is needed to
      understand just how this process unfolds and how retired athletes can be
      supported in developing a healthier and more adaptive approach to eating.

PMID- 27715476
TI  - Individualized Laparoscopic Therapy for Portal Hypertension: A Preliminary Single
      Center Experience.
AB  - BACKGROUND: To investigate the effects and technical points of several
      individualized laparoscopic therapies for patients suffering from cirrhotic
      portal hypertension. METHODS: In total, 385 cirrhotic patients who underwent the
      treatment of individualized laparoscopic therapy from February 2012 to December
      2015 at the Clinical Medical College of Yangzhou University were enrolled in this
      study. We retrospectively analyzed the clinical data and the key technical
      points. RESULTS: Individualized laparoscopic therapies were successfully
      performed on 379 of 385 cases. Six cases were converted to a laparotomy (the rate
      of conversion to laparotomy was 1.6%). Modified laparoscopic splenectomy (MLS)
      for cirrhotic patients with hypersplenism was successfully performed on 103 of
      105 cases. Laparoscopic azygoportal disconnection for cirrhotic patients with
      esophagogastric variceal bleeding (EGVB) or F3 varices was successfully performed
      on 61 of 62 cases, and modified laparoscopic splenectomy and azygoportal
      disconnection (MLSD) for cirrhotic patients with hypersplenism and EGVB or F3
      varices was successfully performed on 196 of 201 cases. Synchronous MLS and
      laparoscopic partial hepatectomy (SLSH) for cirrhotic patients with hypersplenism
      and hepatocellular carcinoma (HCC) and synchronous MLSD and laparoscopic partial
      hepatectomy (SLSDH) for cirrhotic patients with hypersplenism, EGVB or F3 varices
      and HCC were all successfully implemented on 12 and 5 patients, respectively.
      From May 2013, we used the intraoperative autologous cell salvage during each
      individualized laparoscopic procedure. CONCLUSIONS: An individualized
      laparoscopic therapy was beneficial for different state of selected cirrhotic
      patients with portal hypertension with or without HCC.

PMID- 27715477
TI  - Translation and validation of the Chinese versions of the Suicidal Ideation
      Attributes Scale, Stigma of Suicide Scale, and Literacy of Suicide Scale.
AB  - This article reports the validation of the Chinese versions of the Suicidal
      Ideation Attributes Scale (SIDAS), the short form of Stigma of Suicide Scale
      (SOSS), and the short form of Literacy of Suicide Scale (LOSS) among 57 Chinese
      and English bilinguals and 224 Chinese university students. All the translated
      scales showed high correlations with the original versions. The translated SIDAS
      and refined SOSS demonstrated robust factor structures, good internal
      consistency, and convergent validity. Chinese students with self-reported
      depression symptoms tended to have higher glorification of suicide and lower
      suicide literacy. These brief scales fill an important gap in evaluating suicide
      outcomes in Chinese-speaking societies.

PMID- 27715479
TI  - Effects of Visual Error Timing on Smooth Pursuit Gain Adaptation in Humans.
AB  - Smooth pursuit (SP) is one of the precise oculomotor behaviors when tracking a
      moving object. Adaptation of SP is based on a visual-error driven motor learning
      process associated with predictable changes in the visual environment. Proper
      timing of a sensory signal is an important factor for adaptation of fine motor
      control. In this study, we investigated whether visual error timing affects SP
      gain adaptation. An adaptive change in SP gain is produced experimentally by
      repeated trials of a step-ramp tracking with 2 different velocities (double
      velocity paradigm). The authors used the double-velocity paradigm where target
      speed changes 400 or 800 ms after the target onset. The results show that SP gain
      changed in a certain time window following adaptation. The authors suggest that
      SP adaptation shown in this study is associated with timing control mechanisms.

PMID- 27715480
TI  - The Effect of External and Internal Focus of Attention on Gait Variability in
      Older Adults.
AB  - Internal focus of attention on a movement or focusing on an external target are
      both strategies that can affect motor performance. The authors explored whether
      manipulating subjects' focus of attention while walking would alter gait
      variability, a measure reflecting consistency of gait and associated with the
      risk of falling in older adults. Twenty community-living older adults
      participated in the study and were tested while focusing their attention on (a)
      gait consistency (internal focus) or (b) metronome beats (external focus). In
      both conditions gait variability increased (i.e., worsened p < .05) or did not
      change. No benefit was found in instructing subjects to focus on gait consistency
      or metronome beats. Such instructions may actually have distracted and interfered
      with the execution of gait.

PMID- 27715481
TI  - Evaluation of trace metal levels in surface water and sediments of the Hungarian
      upper section of the Danube River and its tributaries.
AB  - The objective of this study was to assess the concentration levels of trace
      metals (Zn, Hg, Cd, Cr, Ni, Pb and Cu) in surface water and bottom sediments of
      the Hungarian upper section of the Danube River and its main tributaries. A total
      of 935 samples (water and sediments) were collected from 10 different sampling
      sites in the period of 2001-2012 and analyzed for the trace metals. Moreover, the
      dissolved arsenic content was determined in a number of 467 water samples in the
      period of 2004-2012. The highest dissolved trace element concentrations were
      observed at the site of Kenyermezei-patak Creek located near a hazardous waste
      incinerator. However, the comparison of the dissolved trace metal(loid)
      concentrations determined with other sections of the Danube River and the
      European Union environmental quality standards revealed that the dissolved trace
      metal(loid) concentrations were relatively low in the Hungarian upper section
      during the 12-year study period (excluding some samples for Hg, Cd and Cr). The
      concentrations of trace metals in sediments were higher than those found in water
      samples and varied very much in all sampling sites during the study period. The
      sediment samples were mainly classified as low or moderate polluted for trace
      metals. However, some sediment samples collected especially from the Moson Danube
      branch indicated a considerable (for Zn, Hg, Cd, Ni and Cu) or a very high (for
      Zn and Hg) contamination.

PMID- 27715478
TI  - In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons,
      and comprehensive selection strategies.
AB  - Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences
      that bind to a specific target molecule with high affinity and specificity
      through their ability to adopt 3-dimensional structure in solution. Aptamers have
      huge potential as targeted therapeutics, diagnostics, delivery agents and as
      biosensors. However, aptamers composed of natural nucleotide monomers are quickly
      degraded in vivo and show poor pharmacodynamic properties. To overcome this,
      chemically-modified nucleic acid aptamers are developed by incorporating modified
      nucleotides after or during the selection process by Systematic Evolution of
      Ligands by EXponential enrichment (SELEX). This review will discuss the
      development of chemically-modified aptamers and provide the pros and cons, and
      new insights on in vitro aptamer selection strategies by using chemically
      modified nucleic acid libraries.

PMID- 27715482
TI  - Calcified cephalohematoma as an unusual cause of EEG anomalies: case report.
AB  - Cephalohematoma, one of the most common neonatal head injuries, generally
      undergoes spontaneous resorption. When calcified, it may cause cranial vault
      distortion and depression of the inner skull layer, although it remains
      asymptomatic. Surgery, indeed, is usually performed for cosmetic purposes. For
      these reasons, the long-term effects of calcified cephalohematoma (CC) are widely
      unknown. The authors report the case of an 11-year-old girl with a persistent
      calcified CC causing skull deformity and delayed electroencephalography (EEG)
      anomalies. These anomalies were detected during routine control EEG and were not
      clinically evident. The young girl underwent surgical removal of the CC for
      cosmetic purpose. The EEG abnormalities disappeared after surgery, thus
      reinforcing the hypothesis of a correlation with the brain "compression"
      resulting from the CC. To the best of the authors' knowledge this is the first
      time that CC-associated EEG anomalies have been described: even though these
      anomalies cannot be considered an indication for surgery, they merit late follow
      up in case of skull deformity.

PMID- 27715483
TI  - Letter to the Editor: Endoscopic resection of intraventricular choroid plexus
      papillomas in infants.

PMID- 27715484
TI  - Characteristics of infarction after encephaloduroarteriosynangiosis in young
      patients with moyamoya disease.
AB  - OBJECTIVE Young patients with moyamoya disease can exhibit infarction after
      revascularization surgery. This analysis of the characteristics of infarction
      after encephaloduroarteriosynangiosis (EDAS) in young patients with moyamoya
      disease was undertaken in an effort to elucidate the infarction mechanism.
      METHODS The authors retrospectively collected clinical information and reviewed
      pre- and postoperative MRI studies from cases involving patients younger than 18
      years who underwent EDAS for the treatment of moyamoya disease between January
      2012 and February 2015. Infarction patterns were categorized into watershed,
      territorial, or mixed pattern. The Wilcoxon rank sum test, chi-square test, and
      Fisher exact test were used to compare the clinical and imaging variables between
      patient groups. The characteristics of patients with and without postoperative
      infarction were compared using univariate and multivariate analysis. The
      cumulative proportion of patients without postoperative infarction according to
      operation stage was calculated using the Kaplan-Meier method and the resulting
      curves were compared using the log-rank test. RESULTS In 100 patients, 171 EDAS
      procedures had been performed. There were 38 cases of preoperative infarction in
      35 patients and 20 cases of postoperative infarction in 13 patients. Territorial
      infarction was more frequent in the postoperative infarction group than in the
      preoperative infarction group (55.0% vs 37.8%, p = 0.037). Infarction was more
      common on the bilateral or contralateral side of the operation after first-stage
      EDAS (9 [75.0%] of 12 infarctions) than in the second-stage operation (2 [25.0%]
      of 8 infarctions), but the difference was not statistically significant (p =
      0.068). The frequency of postoperative infarction was not significantly different
      depending on the stage of the operation (p = 0.694). CONCLUSIONS An acute
      infarction pattern after EDAS was more frequently territorial, suggesting an
      underlying occlusive mechanism. Operation stage did not affect the rate of
      postoperative infarction occurrence.

PMID- 27715486
TI  - Spin-echo Echo-planar Imaging MR Elastography versus Gradient-echo MR
      Elastography for Assessment of Liver Stiffness in Children and Young Adults
      Suspected of Having Liver Disease.
AB  - Purpose To compare two-dimensional (2D) gradient-recalled echo (GRE) and 2D spin
      echo (SE) echo-planar imaging (EPI) magnetic resonance (MR) elastography for
      measurement of hepatic stiffness in pediatric and young adult patients suspected
      of having liver disease. Materials and Methods In this institutional review board
      approved, HIPAA-compliant study, 58 patients underwent both 2D GRE and 2D SE-EPI
      MR elastography at 1.5 T during separate breath holds. Liver stiffness (mean of
      means; in kilopascals) was measured by five blinded reviewers. Pooled mean liver
      stiffness and region-of-interest (ROI) size were compared by using paired t
      tests. Intraclass correlation coefficients (ICCs) were used to assess agreement
      between techniques. Respiratory motion artifacts were compared across sequences
      by using the Fisher exact test. Results Mean patient age was 14.7 years +/- 5.2
      (standard deviation; age range, 0.7-20.5 years), and 55.2% (32 of 58) of patients
      were male. Mean liver stiffness was 2.92 kPa +/- 1.29 measured at GRE MR
      elastography and 2.76 kPa +/- 1.39 at SE-EPI MR elastography (n = 290; P = .15).
      Mean ROI sizes were 8495 mm2 +/- 4482 for 2D GRE MR elastography and 15 176 mm2
      +/- 7609 for 2D SE-EPI MR elastography (n = 290; P < .001). Agreement was
      excellent for measured stiffness between five reviewers for both 2D GRE (ICC,
      0.97; 95% confidence interval: 0.95, 0.98) and 2D SE-EPI (ICC, 0.98; 95%
      confidence interval: 0.96, 0.99). Mean ICC (n = 5) for agreement between 2D GRE
      and 2D SE-EPI MR elastography was 0.93 (range, 0.91-0.95). Moderate or severe
      breathing artifacts were observed on 27.5% (16 of 58) of 2D GRE images versus 0%
      2D SE-EPI images (P < .001). Conclusion There is excellent agreement on measured
      hepatic stiffness between 2D GRE and 2D SE-EPI MR elastography across multiple
      reviewers. SE-EPI MR elastography allowed for stiffness measurement across larger
      areas of the liver and can be performed in a single breath hold. (c) RSNA, 2016.

PMID- 27715485
TI  - Constructive edge of uridylation-induced RNA degradation.
AB  - RNA uridylation is a significant transcriptome-shaping factor in protists, fungi,
      metazoans, and plants. The 3' U-additions are catalyzed by terminal
      uridyltransferases (TUTases), a diverse group of enzymes that along with non
      canonical poly(A) polymerases form a distinct group in the superfamily of DNA
      polymerase beta-like nucleotidyl transferases. Within and across studied
      organisms and subcellular compartments, TUTases differ in nucleotide triphosphate
      selectivity, interacting partners, and RNA targets. A general premise linking RNA
      uridylation to 3'-5' degradation received support from several studies of small
      RNAs and mRNA turnover. However, recent work on kinetoplastid protists typified
      by Trypanosoma brucei provides evidence that RNA uridylation may play a more
      nuanced role in generating functional small RNAs. In this pathogen's
      mitochondrion, most mRNAs are internally edited by U-insertions and deletions,
      and subjected to 3' adenylation/uridylation; guide RNAs (gRNAs) required for
      editing are U-tailed. The prominent role of uridylation in mitochondrial RNA
      metabolism stimulated identification of the first TUTase, RNA editing TUTase 1
      (RET1). Here we discuss functional studies of mitochondrial uridylation in
      trypanosomes that have revealed an unorthodox pathway of small RNA biogenesis.
      The current model accentuates physical coupling of RET1 and 3'-5' RNase II/RNB
      type exonuclease DSS1 within a stable complex termed the mitochondrial 3'
      processome (MPsome). In the confines of this complex, RET1 initially uridylates a
      long precursor to activate its 3'-5' degradation by DSS1, and then uridylates
      trimmed guide RNA to disengage the processing complex from the mature molecule.
      We also discuss a potential role of antisense transcription in the MPsome pausing
      at a fixed distance from gRNA's 5' end. This step likely defines the mature 3'
      end by enabling kinetic competition between TUTase and exonuclease activities.

PMID- 27715487
TI  - The eponymous legacy of Sir William Richard Gowers (1845-1915): A revealing
      letter.
AB  - The eponymous legacy of Sir William Richard Gowers (1845-1915) was the subject of
      a comprehensive appraisal first written for this journal late last year. Since
      the completion of that work, a revealing February 1903 letter has come to light
      recording, amongst other things, Gowers' firsthand and somewhat private opinions
      concerning some of his own eponymous contributions to medicine. This addendum to
      the primary author's original article will review and contextualize this very
      interesting find as it relates to Gowers' eponymous legacy. Gowers' "ataxic
      paraplegia" (referred to as "Gowers' disease" in the letter) and "syringal
      hemorrhage" are specially considered, and his broader neological contributions
      are also briefly addressed. For completion, a number of other previously
      unnoticed eponyms are added to the already impressive list of medical entities
      named in Gowers' honor, and a more complete collection of eponyms found in
      Gowers' Manual are tabulated for consideration.

PMID- 27715489
TI  - Problematic clinical features of children and adults with cerebral palsy who use
      electric powered indoor/outdoor wheelchairs: A cross-sectional study.
AB  - This article aims to describe the clinical features of electric powered
      indoor/outdoor wheelchair (EPIOC) users with cerebral palsy (CP) that are
      problematic to optimal prescription and to explore comorbidities, features of CP,
      and conditions secondary to disability impacting on equipment provision for
      children and adults. The method is a cross-sectional study of EPIOC users (n =
      102) with a primary diagnosis of CP. This is a retrospective review of electronic
      and case note records of EPIOC recipients attending a specialist wheelchair
      service in 2007-2008. Records were reviewed by a rehabilitation consultant. Data
      were extracted under three themes; demographic, diagnostic/clinical and
      wheelchair factors. There were 48 males mean age 27.5 (range 8-70, SD 13.9) years
      and 54 females, mean age 29.5 (range 7-68, SD 14.6) years with CP. Sixteen
      comorbidities, nine features of CP, and five features of disability influenced
      wheelchair prescription. Sixty-four users were provided with specialized seating
      (SS) and 47 with tilt-in-space (TIS) seats. Complex controls were provided to 16
      users, 12 tray-mounted. The majority of users had both SS and TIS. Powered
      wheelchair prescription has important therapeutic roles in clinical management in
      addition to enhancing mobility, independence and participation. Clinical features
      such as spasticity and problematic pain appeared less well managed in adults than
      in children.

PMID- 27715488
TI  - Changes in Multidigit Synergies and Their Feed-Forward Adjustments in Multiple
      Sclerosis.
AB  - The authors explored the changes in multidigit synergies in patients with
      multiple sclerosis (MS) within the framework of the uncontrolled manifold
      hypothesis. The specific hypotheses were that both synergy indices and
      anticipatory synergy adjustments prior to the initiation of a self-paced quick
      action would be diminished in the patients compared to age-matched controls. The
      MS patients and age-matched controls (n = 13 in both groups) performed one-finger
      and multifinger force production tasks involving both accurate steady-state force
      production and quick force pulses. The patients showed significantly lower
      maximal finger forces and a tendency toward slower force pulses. Enslaving was
      increased in MS, but only in the lateral fingers (index and little). Indices of
      multifinger synergies during steady-state force production were lower in MS,
      mainly due to the lower amount of intertrial variance that did not affect total
      force. Anticipatory synergy adjustments were significantly delayed in MS. The
      results show that MS leads to significant changes in multidigit synergies and
      feed-forward adjustments of the synergies prior to a quick action. The authors
      discuss possible contributions of subcortical structures to the impaired synergic
      control.

PMID- 27715490
TI  - Post-transcriptional mending of gene sequences: Looking under the hood of
      mitochondrial gene expression in diplonemids.
AB  - The instructions to make proteins and structural RNAs are laid down in gene
      sequences. Yet, in certain instances, these primary instructions need to be
      modified considerably during gene expression, most often at the transcript level.
      Here we review a case of massive post-transcriptional revisions via trans
      splicing and RNA editing, a phenomenon occurring in mitochondria of a recently
      recognized protist group, the diplonemids. As of now, the various post
      transcriptional steps have been cataloged in detail, but how these processes
      function is still unknown. Since genetic manipulation techniques such as gene
      replacement and RNA interference have not yet been established for these
      organisms, alternative strategies have to be deployed. Here, we discuss the
      experimental and bioinformatics approaches that promise to unravel the molecular
      machineries of trans-splicing and RNA editing in Diplonema mitochondria.

PMID- 27715491
TI  - Objective Evaluation of Performance Stress in Musicians With Focal Hand Dystonia:
      A Case Series.
AB  - Five musicians suffering from focal dystonia participated in a pilot study that
      examined the feasibility of an experimental protocol designed to assess
      musicians' motor performance under stress. Electrocardiography, free cortisol
      levels, and subjective assessments were used to monitor alterations of the
      hypothalamic-pituitary-adrenal axis. As measures of motor outcome, temporal
      variability of finger movements and muscular cocontraction of the wrist flexor
      and extensor were assessed. Findings suggest that the specific experimental
      design could be successfully applied. Several methodological issues such as
      carryover effects, the use of free cortisol, the inclusion of a double baseline,
      and the classification of dystonic patients into stress responders and
      nonresponders are analyzed and discussed.

PMID- 27715494
TI  - Spanish Validation of the Polymorphous Prejudice Scale in a Sample of University
      Students.
AB  - The shortened version of the Polymorphous Prejudice Scale (PPS) analyzes new
      manifestations of prejudice toward gay men and lesbian women. Specifically, this
      instrument consists of 16 items distributed in four subscales: values gay
      progress, positive beliefs about gay men, positive beliefs about lesbian women
      and, resistance to heteronormative expectations. The aim of the current study is
      to add new evidence about the reliability and validity of the scale. The scale is
      administrated to 348 heterosexual university students from Spain with a mean age
      of 22.62 years (SD = 7.63). Reliability and factorial validity estimates are
      presented. A four-factor structure is supported using confirmatory factor
      analysis (short version). Our results can be useful in planning variables for
      intervention programs designed to foster the tolerance and normality of sexual
      diversity.

PMID- 27715492
TI  - Connecting G protein signaling to chemoattractant-mediated cell polarity and
      cytoskeletal reorganization.
AB  - The directional movement toward extracellular chemical gradients, a process
      called chemotaxis, is an important property of cells. Central to eukaryotic
      chemotaxis is the molecular mechanism by which chemoattractant-mediated
      activation of G-protein coupled receptors (GPCRs) induces symmetry breaking in
      the activated downstream signaling pathways. Studies with mainly Dictyostelium
      and mammalian neutrophils as experimental systems have shown that chemotaxis is
      mediated by a complex network of signaling pathways. Recently, several labs have
      used extensive and efficient proteomic approaches to further unravel this dynamic
      signaling network. Together these studies showed the critical role of the
      interplay between heterotrimeric G-protein subunits and monomeric G proteins in
      regulating cytoskeletal rearrangements during chemotaxis. Here we highlight how
      these proteomic studies have provided greater insight into the mechanisms by
      which the heterotrimeric G protein cycle is regulated, how heterotrimeric G
      proteins-induced symmetry breaking is mediated through small G protein signaling,
      and how symmetry breaking in G protein signaling subsequently induces
      cytoskeleton rearrangements and cell migration.

PMID- 27715495
TI  - Motor Planning Influences the Perceived Timing of Vibrotactile Stimuli in an
      Amplitude-Dependent Manner.
AB  - The authors characterized how motor planning influences temporal order judgment
      (TOJ) tasks. They examined this by applying vibrotactile stimulation during the
      planning stages of a bimanual arm movement that would bring the arms into a
      crossed configuration. The authors have previously shown that planning to cross
      the arms induces a subjective reversal of spatially defined temporal order
      judgments that evolves over the course of the planning period. It was unclear,
      however, whether this effect is modulated by the extent to which the arms would
      be crossed after movement. The authors examined this issue by having participants
      plan to move to 4 different targets that would leave the arms in crossed
      configurations of varying extents. The results demonstrate that even though
      cutaneous stimuli were applied before the movements, if participants were
      planning to move into a more crossed configuration, performance on the TOJ task
      worsened depending on where they were in the planning process. This data suggest
      the brain uses planning signals to predict sensations from impending movements in
      a context-dependent manner.

PMID- 27715493
TI  - Phosphorylation of the Cajal body protein WRAP53beta by ATM promotes its
      involvement in the DNA damage response.
AB  - The cellular response to DNA double-strand breaks is orchestrated by the protein
      kinase ATM, which phosphorylates key actors in the DNA repair network. WRAP53beta
      is a multifunctional protein that controls trafficking of factors to Cajal
      bodies, telomeres and DNA double-strand breaks but what regulates the involvement
      of WRAP53beta in these separate processes remains unclear. Here, we show that in
      response to various types of DNA damage, including IR and UV, WRAP53beta is
      phosphorylated on serine residue 64 by ATM with a time-course that parallels its
      accumulation at DNA lesions. Interestingly, recruitment of phosphorylated
      WRAP53beta (pWRAP53betaS64) to sites of such DNA damage promotes its interaction
      with gammaH2AX at these locations. Moreover, pWRAP53betaS64 stimulates the
      accumulation of the repair factor 53BP1 at DNA double-strand breaks and enhances
      repair of this type of damage via homologous recombination and non-homologous end
      joining. At the same time, phosphorylation of WRAP53beta is dispensable for its
      localization to Cajal bodies, where it accumulates even in unstressed cells.
      These findings not only reveal ATM to be an upstream regulator of WRAP53beta, but
      also indicates that phosphorylation of WRAP53beta at serine 64 controls its
      involvement in the DNA damage response and may also restrict its other functions.

PMID- 27715496
TI  - Neural Efficiency in Expert Cognitive-Motor Performers During Affective
      Challenge.
AB  - Skilled individuals demonstrate a spatially localized or relatively lower
      response in brain activity characterized as neural efficiency when performing
      within their domain of expertise. Elite athletes are experts in their chosen
      sport and thus must be not only adept in the motor domain but must be resilient
      to performing under the stress of high-level competition. Such stability of
      performance suggests this population processes emotion and mental stress in an
      adaptive and efficient manner. This study sought to determine if athletes with a
      history of successful performance under circumstances of mental stress
      demonstrate neural efficiency during affective challenges compared to age-matched
      controls. Using functional magnetic resonance imaging, the blood-oxygen level
      dependent response was recorded during emotional challenge induced by sport
      specific and general unpleasant images. The athletes demonstrated neural
      efficiency in brain regions critical to emotion regulation (prefrontal cortex)
      and affect (insula) independently of their domain of expertise, suggesting
      adaptive processing of negative events and less emotional reactivity to
      unpleasant stimuli.

PMID- 27715497
TI  - Application of 1D and 2D MFR reactor technology for the isolation of insecticidal
      and anti-microbial properties from pyrolysis bio-oils.
AB  - Valuable chemicals can be separated from agricultural residues by chemical or
      thermochemical processes. The application of pyrolysis has already been
      demonstrated as an efficient means to produce a liquid with a high concentration
      of desired product. The objective of this study was to apply an insect and
      microorganism bioassay-guided approach to separate and isolate pesticidal
      compounds from bio-oil produced through biomass pyrolysis. Tobacco leaf
      (Nicotianata bacum), tomato plant (Solanum lycopersicum), and spent coffee
      (Coffea arabica) grounds were pyrolyzed at 10 degrees C/min from ambient to 565
      degrees C using the mechanically fluidized reactor (MFR). With one-dimensional
      (1D) MFR pyrolysis, the composition of the product vapors varied as the reactor
      temperature was raised allowing for the selection of the temperature range that
      corresponds to vapors with a high concentration of pesticidal properties. Further
      product separation was performed in a fractional condensation train, or 2D MFR
      pyrolysis, thus allowing for the separation of vapor components according to
      their condensation temperature. The 300-400 degrees C tobacco and tomato bio-oil
      cuts from the 1D MFR showed the highest insecticidal and anti-microbial activity
      compared to the other bio-oil cuts. The 300-350 and 350-400 degrees C bio-oil
      cuts produced by 2D MFR had the highest insecticidal activity when the bio-oil
      was collected from the 210 degrees C condenser. The tobacco and tomato bio-oil
      had similar insecticidal activity (LC50 of 2.1 and 2.2 mg/mL) when the bio-oil
      was collected in the 210 degrees C condenser from the 300-350 degrees C reactor
      temperature gases. The 2D MFR does concentrate the pesticidal products compared
      to the 1D MFR and thus can reduce the need for further separation steps such as
      solvent extraction.

PMID- 27715498
TI  - Subjective Well-Being and Levels of Clinical Symptomatology in a Transwomen
      Sample and Men Who Have Sex with Men in Chile.
AB  - This paper examines the levels of subjective well-being (psychological and social
      well-being, subjective happiness, and satisfaction with life) and clinical
      symptomatology (anxiety, depression, somatization, hostility, and phobic anxiety)
      in a transwomen sample (n = 112). The sample was recruited through a snowball
      procedure in Chile (Santiago, Valparaiso, and Arica). Data obtained are compared
      to those from a group of Men who have Sex with Men (MSM) (n = 323). Results
      reveal statistically significant differences in the levels of happiness (t(157) =
      2.16; p = .03; d = .25), satisfaction with life (t(154) = 3.90; p < .001; d =
      .47), and purpose in life (scale of psychological well-being) (t(151) = 1.99; p
      .04; d = .24) reported by the two groups. The transwomen group shows the lowest
      scores in all dimensions. However, trans women report higher levels of social
      coherence (t(432) = -4.96; p < .001; d = .53) on the social well-being scale,
      compared to the MSM group. Regarding their levels of clinical symptomatology,
      trans women report higher levels of anxiety (t(163) = -6.67; p < .001; d = .78),
      depression (t(167) = -5.61; p < .001; d = .65), somatization (t(161) = -5.10; p <
      .001; d = .60), hostility (t(153) = -5.38; p < .001; d = .62), and phobic anxiety
      (t(164) = -6.70; p < .001; d = .80). Results are discussed on the basis of the
      context of each group.

PMID- 27715499
TI  - Biodegradation of malathion, alpha- and beta-endosulfan by bacterial strains
      isolated from agricultural soil in Veracruz, Mexico.
AB  - The objective of this study was to evaluate the capacity of two bacterial strains
      isolated, cultivated, and purified from agricultural soils of Veracruz, Mexico,
      for biodegradation and mineralisation of malathion (diethyl 2
      (dimethoxyphosphorothioyl) succinate) and alpha- and beta-endosulfan
      (6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6-9-methano-2,4,3
      benzodioxathiepine-3-oxide). The isolated bacterial strains were identified using
      biochemical and morphological characterization and the analysis of their 16S rDNA
      gene, as Enterobacter cloacae strain PMM16 (E1) and E. amnigenus strain XGL214
      (M1). The E1 strain was able to degrade endosulfan, whereas the M1 strain was
      capable of degrading both pesticides. The E1 strain degraded 71.32% of alpha
      endosulfan and 100% of beta-endosulfan within 24 days. The absence of
      metabolites, such as endosulfan sulfate, endosulfan lactone, or endosulfan diol,
      would suggest degradation of endosulfan isomers through non-oxidative pathways.
      Malathion was completely eliminated by the M1 strain. The major metabolite was
      butanedioic acid. There was a time-dependent increase in bacterial biomass,
      typical of bacterial growth, correlated with the decrease in pesticide
      concentration. The CO2 production also increased significantly with the addition
      of pesticides to the bacterial growth media, demonstrating that, under aerobic
      conditions, the bacteria utilized endosulfan and malathion as a carbon source.
      Here, two bacterial strains are shown to metabolize two toxic pesticides into non
      toxic intermediates.

PMID- 27715500
TI  - Self-reported occupational injuries among industrial beef slaughterhouse workers
      in the Midwestern United States.
AB  - Although workers in meatpacking facilities in the U.S. experience high rates of
      occupational injury, their injury experiences have received limited research
      attention. Prior research indicates underreporting in injury rates in this
      industry as well significant variation in injury rates among facilities. To add
      detail to the rates and circumstances surrounding occupational injury among
      meatpacking workers, we conducted a cross-sectional study of workers employed at
      an industrial beefpacking plant in Nebraska (n = 137) and interviewed workers
      about recent injury experiences. We assessed frequency, cause and nature of self
      reported injury. We estimated annual incidence rates of self-reported injuries
      using the OSHA formula and compared these rates to industry-wide data. We also
      evaluated psychological distress in this workforce as measured by the Kessler-6
      scale to assess whether distress was associated with recent occupational injury.
      In this study, 15.1% of workers experienced occupational injuries that required
      time off work, job transfer, or restriction during the past three months. The
      estimated annual incidence rate was 15.2 injuries per 100 full-time workers for
      these injuries at this plant. Rushing was identified as the cause of nearly 50%
      of injuries, and repetitive work as the cause of an additional 20% of injuries.
      Use of metal mesh sleeves (POR: 0.10 (p = 0.008)) and metal mesh gloves (POR:
      0.41 (p = 0.05) were associated with reduced risk of injury. Use of a carbon
      steel for knife sharpening (POR: 5.2 (p = 0.02)) was associated with elevated
      risk of moderate and severe injury. There were no associations between self
      reported occupational injury and overall measures of psychological distress. Self
      reported incidence rate of severe injury in this plant was more than twice
      official industry estimates. Worker self-reports may illustrate key areas for
      injury prevention.

PMID- 27715502
TI  - Settlement behavior of municipal solid waste due to internal and external
      environmental factors in a lysimeter.
AB  - Long-term settlement magnitude is influenced by changes in external and internal
      factors that control the microbiological activity in the landfill waste body. To
      improve the understanding of settlement phenomena, it is instructive to study
      lysimeters filled with MSW. This paper aims to understand the settlement behavior
      of MSW by correlating internal and external factors that influence waste
      biodegradation in a lysimeter. Thus, a lysimeter was built, instrumented and
      filled with MSW from the city of Campina Grande, the state of Paraiba, Brazil.
      Physicochemical analysis of the waste (from three levels of depth of the
      lysimeter) was carried out along with MSW settlement measurements. Statistical
      tools such as descriptive analysis and principal component analysis (PCA) were
      also performed. The settlement/compression, coefficient of variation and PCA
      results indicated the most intense rate of biodegradation in the top layer. The
      PCA results of intermediate and bottom levels presented fewer physicochemical and
      meteorological variables correlated with compression data in contrast with the
      top layer. It is possible to conclude that environmental conditions may influence
      internal indicators of MSW biodegradation, such as the settlement.

PMID- 27715503
TI  - Aerobic Fitness Is Associated With Cognitive Control Strategy in Preadolescent
      Children.
AB  - The authors used a conditional accuracy function (CAF) method to compute the mean
      accuracy of multiple reaction time ranges, to investigate the association between
      aerobic fitness and the utilization of cognitive control strategy during
      preadolescence. Thirty-eight higher- and lower-fit children were grouped
      according to their cardiorespiratory capacity (VO2max) and completed a modified
      flanker task. Seventeen young adults were recruited as a reference group of
      maturation. The results showed that higher-fit children exhibited an adult-like
      performance pattern, and demonstrated increased overall response accuracy
      compared to lower-fit children, with a disproportionally larger increase in
      individual responses when the time allowed for discriminative processing was
      constrained. These findings suggest that aerobic fitness is associated with
      enhanced cognitive control and development of a more proactive control strategy
      during flanker task in preadolescent children.

PMID- 27715504
TI  - Eco-friendly PEG-based controlled release nano-formulations of Mancozeb:
      Synthesis and bioefficacy evaluation against phytopathogenic fungi Alternaria
      solani and Sclerotium rolfsii.
AB  - Controlled release (CR) nano-formulations of Mancozeb (manganese-zinc double salt
      of N,N-bisdithiocarbamic acid), a protective fungicide, have been prepared using
      laboratory-synthesized poly(ethylene glycols) (PEGs)-based functionalized
      amphiphilic copolymers without using any surfactants or external additives. The
      release kinetics of the developed Mancozeb CR formulations were studied and
      compared with that of commercially available 42% suspension concentrate and 75%
      wettable powder. Maximum amount of Mancozeb was released on 42nd day for PEG-600
      and octyl chain, PEG-1000 and octyl chain, and PEG-600 and hexadecyl chain, on
      35th day for PEG-1000 and hexadecyl chain, on 28th day for PEG-1500 and octyl
      chain, PEG-2000 and octyl chain, PEG-1500 and hexadecyl chain, and PEG-2000 and
      hexadecyl chain in comparison to both commercial formulations (15th day). The
      diffusion exponent (n value) of Mancozeb in water ranged from 0.42 to 0.62 in
      tested formulations. The half-release (t1/2) values ranged from 17.35 to 35.14
      days, and the period of optimum availability of Mancozeb ranged from 18.54 to
      35.42 days. Further, the in vitro bioefficacy evaluation of developed
      formulations was done against plant pathogenic fungi Alternaria solani and
      Sclerotium rolfsii by poison food technique. Effective dose for 50% inhibition in
      mgL-1 (ED50) values of developed formulations varied from 1.31 to 2.79 mg L-1 for
      A. solani, and 1.60 to 3.14 mg L-1 for S. rolfsii. The present methodology is
      simple, economical, and eco-friendly for the development of environment-friendly
      CR formulations of Mancozeb. These formulations can be used to optimize the
      release of Mancozeb to achieve disease control for the desired period depending
      upon the matrix of the polymer used. Importantly, the maximum amount of active
      ingredient remains available for a reasonable period after application. In
      addition, the developed CR formulations were found to be suitable for fungicidal
      applications, allowing use of Mancozeb in lower doses.

PMID- 27715501
TI  - Putative RNA-Directed Adaptive Mutations in Cancer Evolution.
AB  - Understanding the molecular mechanisms behind the capacity of cancer cells to
      adapt to the tumor microenvironment and to anticancer therapies is a major
      challenge. In this context, cancer is believed to be an evolutionary process
      where random mutations and the selection process shape the mutational pattern and
      phenotype of cancer cells. This article challenges the notion of randomness of
      some cancer-associated mutations by describing molecular mechanisms involving
      stress-mediated biogenesis of mRNA-derived small RNAs able to target and increase
      the local mutation rate of the genomic loci they originate from. It is proposed
      that the probability of some mutations at specific loci could be increased in a
      stress-specific and RNA-depending manner. This would increase the probability of
      generating mutations that could alleviate stress situations, such as those
      triggered by anticancer drugs. Such a mechanism is made possible because tumor-
      and anticancer drug-associated stress situations trigger both cellular
      reprogramming and inflammation, which leads cancer cells to express molecular
      tools allowing them to "attack" and mutate their own genome in an RNA-directed
      manner.

PMID- 27715604
TI  - Impact of single anaerobic exercise on delayed activation of endothelial xanthine
      oxidase in men and women.
AB  - OBJECTIVES: The aim of the study was to evaluate the activity of xanthine oxidase
      (XO) in the blood of men and women during the first hour following a single
      anaerobic exercise (AN-EX), and after 24 hours of recovery, and to determine
      whether the changes in XO activity in the blood after AN-EX are dependent on
      anaerobic performance. METHODS: Ten men and ten women performed a single AN-EX.
      Blood was collected before and five times after completion of the AN-EX. The
      activity of XO was determined. RESULTS: In both groups, a significant (P < 0.05)
      increase in blood XO activity was found only 24 hours after the AN-EX. The
      increased activity of XO in men was significantly lower than in women (P < 0.05).
      Negative correlations were found between the increase in XO activity in the blood
      plasma 24 hours after the AN-EX and anaerobic power, the total work performed
      during the AN-EX and the power decrease. DISCUSSION: In the first hour after the
      single AN-EX, XO activity in the blood of women and men did not change, but after
      24 hours of recovery, it was significantly higher compared to baseline levels in
      both sexes. Single AN-EX causes a smaller increase in XO activity in people with
      higher anaerobic performance.

PMID- 27715605
TI  - Modelling anaerobic digestion in a biogas reactor: ADM1 model development with
      lactate as an intermediate (Part I).
AB  - The Anaerobic Digestion Model No. 1 (ADM1) was extended to include lactate, a
      crucial metabolic product during sugar fermentation. This study tests the
      validity of the modified ADM1 model in improving the predictions of a standard
      biogas reactor. This reactor was prepared in the laboratory with simple organic
      substrates with an intention to represent an 'average biogas plant'. Kinetic
      parameters were determined from a lactic acid enriched steady-state reactor. The
      parameters were adjusted further in order to acquire satisfying simulation
      results systematically with the batch experiments and then against the standard
      biogas reactor. Arresting methanogenesis revealed that lactate degradation
      occurred majorly via acetate followed by propionate, and a non-negligible
      proportion of butyrate too was found, which were further updated in the model.
      The modified ADM1 provided a successful correlation with the experimental results
      for the batch and continuous experiments. We justified that inclusion of lactate
      in the model resulted in optimized simulation for both biogas and methane content
      in the standard biogas reactor.

PMID- 27715606
TI  - Self-Criticism and Depressive Symptoms Mediate the Relationship Between Emotional
      Experiences With Family and Peers and Self-Injury in Adolescence.
AB  - Although the relationship between negative childhood experiences, peer
      victimization, depressive symptoms, and Non-Suicidal Self-Injury (NSSI) is widely
      recognized, the mechanisms involved are not fully understood, especially among
      adolescents. This study aims to test the mediating role of both self-criticism
      and depressive symptoms in the relationship between memories of negative or
      positive experiences, current peer victimization, and NSSI. The sample consists
      854 Portuguese adolescents, 451 female and 403 male, with ages between 12 and 18
      years (M = 14.89; SD = 1.79), from middle and secondary schools. Participants
      answered self-report measures. Results from path analysis showed that memories of
      negative experiences, the absence of positive memories with family in childhood
      and peer victimization indirectly impact on NSSI through self-criticism and
      depressive symptoms. In addition, these stressful experiences led to depressive
      symptoms through self-criticism. Lastly, the most severe form of self-criticism
      indirectly impacts on NSSI through depressive symptoms, even though it also has a
      strong direct effect. It suggests that negative experiences with parents and peer
      victimization, as well as the absence of positive memories with family, have a
      negative impact on NSSI when these experiences are linked with a sense of self
      hatred and depressive symptoms.

PMID- 27715607
TI  - Development and validation of the Chinese Death Metaphors Scale-Revised.
AB  - Chinese people tend to use metaphorical expressions and rhetorical figures to
      convey meanings and emotions, and they usually talk about death implicitly. The
      assessment of death metaphors and images can provide a better understanding of
      Chinese personal perceptions of death. This study aimed at modifying the Chinese
      Death Metaphors Scale (CDMS; Cheung, 2005 ) and establishing one that is more
      suitable for Chinese people. Thirty-one death metaphor statements in Chinese were
      created from items of CDMS and an open questionnaire study. The item pool was
      tested with 425 participants and exploratory factor analysis revealed four
      factors (Comfortable/Painful/Sorrowful/Empty), differing with the two-factor
      structure (Positive/Negative) of the original CDMS. On the basis of this, a 24
      item Revised Chinese Death Metaphors Scale was generated. It was carried out to
      473 participants together with Templer's Death Anxiety Scale (DAS) for
      Confirmatory factor analysis, which revealed an acceptable model fit: chi2/df =
      4.05, goodness-of-fit index = .85, adjusted goodness-of-fit index = .82,
      incremental fit index = .90, nonnormed fit index = .90, comparative fit index =
      .90, root mean square error of approximation = .08, all met the criteria
      standards for adequacy of fit. Construct validity, criterion-related validity
      with DAS, and composite reliability were all acceptable and reasonable. The
      Chinese Death Metaphors Scale-Revised is satisfactory and reliable and more
      suitable than previous instruments for use with Chinese people.

PMID- 27715650
TI  - App Factory: A flexible approach to rehabilitation engineering in an era of rapid
      technology advancement.
AB  - This article describes a flexible and effective approach to research and
      development in an era of rapid technological advancement. The approach relies on
      secondary dispersal of grant funds to commercial developers through a competitive
      selection process. This "App Factory" model balances the practical reliance on
      multi-year funding needed to sustain a rehabilitation engineering research center
      (RERC), with the need for agility and adaptability of development efforts
      undertaken in a rapidly changing technology environment. This approach also
      allows us to take advantage of technical expertise needed to accomplish a
      particular development task, and provides incentives to deliver successful
      products in a cost-effective manner. In this article, we describe the App Factory
      structure, process, and results achieved to date; and we discuss the lessons
      learned and the potential relevance of this approach for other grant-funded
      research and development efforts. Data presented on the direct costs and number
      of downloads of the 16 app development projects funded in the App Factory's first
      3 years show that it can be an effective means for supporting focused, short-term
      assistive technology development projects.

PMID- 27715651
TI  - 1H-NMR-based metabolomic study on toxicity of methomyl and methidathion in fish.
AB  - A 1H-nuclear magnetic resonance (NMR) spectroscopy with multivariate analysis was
      applied to detect the toxicity of antiacetylcholinesterase insecticides, methomyl
      (methyl (1E)-N-(methylcarbamoyloxy)ethanimidothioate) and methidathion (3
      (dimethoxyphosphinothioyl sulfanylmethyl)-5-methoxy-1,3,4-thiadiazol-2-one),
      using zebrafish (Danio rerio) and Chinese bleak (Aphyocypris chinensis).
      Generally, methomyl and methidathion have been believed not to highly accumulate
      in fish tissues. However, these pesticides showed their toxicity by altering
      patterns of whole-body metabolites in neurotransmitter balance, energy
      metabolism, oxidative stress, and muscle maintenance in low concentrations. We
      used Pearson correlation analysis to contextualize the metabolic markers in
      pesticide treated groups. We observed that the positive correlations of choline
      with acetate and betaine in untreated control were shifted to null correlations
      showing acetylcholinesterase specific toxicity. This research demonstrated the
      applicability and potential of NMR metabolomics in detecting toxic effects of
      insecticide with a modicum of concentrations in aquatic environment.

PMID- 27715652
TI  - The effect of body armor on saving officers' lives: An analysis using LEOKA data.
AB  - Using the Law Enforcement Officers Killed and Assaulted (LEOKA; 2002-2011)
      database, we examined the life-saving effectiveness of body armor while adjusting
      for a range of confounders not assessed in previous studies. Among the 637
      officers who were shot by a firearm at the torso, those who wore body armor were
      76% less likely to be killed than those who did not wear armor, controlling for
      an array of individual and incident characteristics. A number of factors
      influenced officers' armor wearing behavior include age, BMI, rank, geographic
      region, and type of assignment. Results will inform law enforcement agencies in
      assessing gaps in their current policy and help focus limited resources to
      encourage armor wearing. The investigation of other factors that influence police
      officers' chance of surviving a gun shooting (while controlling for body armor)
      will also have important implications for policies related to sending backup
      officers to police shootings, emergency response, and other critical areas.

PMID- 27715653
TI  - The effect of obesity on postural stability during a standardized lifting task.
AB  - The objective of this study was to assess the effect of obesity on postural
      stability during a standardized lifting task. Twelve young males, six obese and
      six non-obese, completed three replications of repeated six lifts (at a rate of
      six lifts per minutes) at two levels of loads (10% and 25% of capacity) crossed
      with two levels of orientation (0 degrees  and 45 degrees  from sagittal plane).
      Postural stability measures showed that center of pressure sway path and sway
      area were ~21% and ~53% lower with obesity, respectively. Additionally, frequency
      band of amplitude spectrum in the medial lateral direction at 0 degrees  lifting
      orientation was significantly lower with obesity. The results suggest that
      obesity, as measured by body mass index, does not impair balance control in
      healthy young males when lifting load is relative to the capacity.

PMID- 27715654
TI  - A brief review on recent developments of electrochemical sensors in environmental
      application for PGMs.
AB  - This study offers a brief review of the latest developments and applications of
      electrochemical sensors for the detection of Platinum Group Metals (PGMs) using
      electrochemical sensors. In particular, significant advances in electrochemical
      sensors made over the past decade and sensing methodologies associated with the
      introduction of nanostructures are highlighted. Amongst a variety of detection
      methods that have been developed for PGMs, nanoparticles offer the unrivaled
      merits of high sensitivity. Rapid detection of PGMs is a key step to promote
      improvement of the public health and individual quality of life. Conventional
      methods to detect PGMs rely on time-consuming and labor intensive procedures such
      as extraction, isolation, enrichment, counting, etc., prior to measurement. This
      results in laborious sample preparation and testing over several days. This study
      reviewed the state-of-the-art application of nanoparticles (NPs) in
      electrochemical analysis of environmental pollutants. This review is intended to
      provide environmental scientists and engineers an overview of current rapid
      detection methods, a close look at the nanoparticles based electrodes and
      identification of knowledge gaps and future research needs. We summarize
      electrodes that have been used in the past for detection of PGMs. We describe
      several examples of applications in environmental electrochemical sensors and
      performance in terms of sensitivity and selectivity for all the sensors utilized
      for PGMs detection. NPs have promising potential to increase competitiveness of
      electrochemical sensors in environmental monitoring, though this review has
      focused mainly on sensors used in the past decade for PGMs detection. This review
      therefore provides a synthesis of outstanding performances in recent advances in
      the nanosensor application for PGMs determination.

PMID- 27715655
TI  - Thin-Section CT Features of Idiopathic Pulmonary Fibrosis Correlated with Micro
      CT and Histologic Analysis.
AB  - Purpose To elucidate the underlying lung changes responsible for the computed
      tomographic (CT) features of idiopathic pulmonary fibrosis (IPF) and to gain
      insight into the way IPF proceeds through the lungs and progresses over time.
      Materials and Methods Micro-CT studies of tissue cores obtained from explant
      lungs were examined and were correlated 1:1 with a CT study obtained immediately
      before transplantation. Samples for histologic analysis were obtained from
      selected cores. Results In areas with no or minimal abnormalities on CT images,
      small areas of increased attenuation located in or near the interlobular septa
      can be seen on micro-CT studies. In more involved lung areas, the number of
      opacities increases and opacities enlarge and approach each other along the
      interlobular septa, causing a fine reticular pattern on CT images.
      Simultaneously, air-containing structures in and around these opacities arise,
      corresponding with small cysts on CT images. Honeycombing is caused by a
      progressive increase in the number and size of these cystic structures and tissue
      opacities that gradually extend toward the centrilobular region and finally
      replace the entire lobule. At histologic analysis, the small islands of increased
      attenuation very likely correspond with fibroblastic foci. Near these
      fibroblastic foci, an abnormal adjacency of alveolar walls was seen, suggesting
      alveolar collapse. In later stages, normal lung tissue is replaced by a large
      amount of young collagen, as seen in patients with advanced fibrosis. Conclusion
      Fibrosis and cyst formation in patients with IPF seem to start at the periphery
      of the pulmonary lobule and progressively extend toward the core of this anatomic
      lung unit. Evidence was found that alveolar collapse might already be present in
      an early stage when there is only little pulmonary fibrosis. (c) RSNA, 2016.

PMID- 27715656
TI  - Preoperative MR Imaging in Women with Breast Cancer Detected at Screening US.
AB  - Purpose To determine additional cancer yield of magnetic resonance (MR) imaging
      in women with breast cancer detected at screening ultrasonography (US) and to
      identify a subgroup of women who are likely to benefit from preoperative MR
      imaging. Materials and Methods This study was approved by the institutional
      review board, and the requirement for informed consent was waived. A
      retrospective review of 374 women (median age, 48 years; age range, 30-74 years)
      with breast cancer detected at screening US (invasive, n = 321) who underwent
      preoperative breast MR imaging between 2007 and 2013 was performed. Cancer yield
      and positive predictive value of biopsy were calculated. Multivariate logistic
      regression analysis was performed to identify clinical-pathologic features
      associated with additional cancer detected at MR imaging. Results Of 374 women,
      21 (5.6%; 95% confidence interval [CI]: 3.5%, 8.5%) were diagnosed with
      additional cancer (positive predictive value of biopsy, 42.0% [21 of 50 women];
      95% CI: 28%, 57%). Index invasive lobular cancer (ILC) histologic type was
      significantly associated with additional cancer detected at MR imaging (odds
      ratio, 4.0; 95% CI: 1.2, 13.6; P = .03). In women with index invasive cancer,
      premenopausal status (odds ratio, 5.7; 95% CI: 1.2, 35.8; P = .03) and lobular
      histologic type (odds ratio, 3.9; 95% CI: 1.1, 12.3; P = .03) were factors
      associated with additional cancer detected at MR imaging. Conclusion Preoperative
      MR imaging helped to detect additional sites of cancer in 5.6% of women with
      breast cancer detected at screening US. Women with index ILC and premenopausal
      women are more likely to benefit from preoperative MR imaging. (c) RSNA, 2016
      Online supplemental material is available for this article.

PMID- 27715658
TI  - Contemporary Perspectives on Social Work in Acquired Brain Injury: An
      Introduction.
AB  - This special issue of the Journal of Social Work in Disability and
      Rehabilitation, Contemporary Perspectives on Social Work in Acquired Brain
      Injury, has been initiated and coordinated by the International Network of Social
      Workers in Acquired Brain Injury (INSWABI). In introducing the issue, some space
      will be allocated for providing definitions of traumatic brain injury (TBI) and
      acquired brain injury (ABI); outlining the epidemiology and global costs; and
      detailing the impairments and psychosocial impacts for both the person sustaining
      the injury and his/her family. Finally, an outline of the papers contributing to
      this special issue will be detailed, followed by a brief discussion about the
      role of the INSWABI network in promoting best practice in social work within this
      specialty area.

PMID- 27715657
TI  - Self-gated Non-Contrast-enhanced Functional Lung MR Imaging for Quantitative
      Ventilation Assessment in Patients with Cystic Fibrosis.
AB  - Purpose To assess the clinical feasibility of self-gated non-contrast-enhanced
      functional lung (SENCEFUL) magnetic resonance (MR) imaging for quantitative
      ventilation (QV) imaging in patients with cystic fibrosis (CF). Materials and
      Methods Twenty patients with CF and 20 matched healthy volunteers underwent
      functional 1.5-T lung MR imaging with the SENCEFUL imaging approach, in which a
      two-dimensional fast low-angle shot sequence is used with quasi-random sampling.
      The lungs were manually segmented on the ventilation-weighted images to obtain QV
      measurements, which were compared between groups. QV values of the patients were
      correlated with results of pulmonary function testing. Three radiologists rated
      the images for presence of ventilation deficits by means of visual inspection.
      Mann-Whitney U tests, receiver operating characteristic analyses, Spearman
      correlations, and Gwet agreement coefficient analyses were used for statistical
      analysis. Results QV of the entire lungs was lower for patients with CF than for
      control subjects (mean +/- standard deviation, 0.09 mL/mL +/- 0.03 vs 0.11 mL/mL
      +/- 0.03, respectively; P = .007). QV ratios of upper to lower lung halves were
      lower in patients with CF than in control subjects (right, 0.84 +/- 0.2 vs 1.16
      +/- 0.2, respectively [P < .001]; left, 0.88 +/- 0.3 vs 1.11 +/- 0.1,
      respectively [P = .017]). Accordingly, ventilation differences between the groups
      were larger in the upper halves (Delta = 0.04 mL/mL, P <= .001-.002). QV values
      of patients with CF correlated with forced vital capacity (r = 0.7; 95%
      confidence interval [CI]: 0.21, 0.91), residual volume (static hyperinflation, r
      = -0.8; 95% CI: -0.94, 0.42), and forced expiratory volume in 1 second (airway
      obstruction, r = 0.7; 95% CI: 0.21, 0.91). Disseminated small ventilation
      deficits were the most frequent involvement pattern, present in 40% of the
      functional maps in CF versus 8% in the control subjects (P < .001). Conclusion
      SENCEFUL MR imaging is feasible for QV assessment. Less QV, especially in upper
      lung parts, and correlation to vital capacity and to markers for hyperinflation
      and airway obstruction were found in patients with CF. (c) RSNA, 2016.

PMID- 27715659
TI  - Is There a Correlation Between Static and Dynamic Postural Balance Among Young
      Male and Female Dancers?
AB  - Aimed to investigate whether young male and female dancers have different
      patterns of association between static and dynamic postural balance (PB), 60
      dancers from the Australian Ballet School (14-19 years old) were tested for
      static and dynamic PB with head and lumbar accelerometers. Monotonic
      relationships between static and dynamic PB were found in head movements among
      young female dancers in all three directions, but were found for young male
      dancers in the mediolateral (ML) and anteroposterior (AP) directions only. In
      lumbar movements, monotonic relationships were found for young female dancers in
      the AP direction only. Comparing head with lumbar movements in static PB, young
      male dancers demonstrated monotonic relationships between head and lumbar
      movements in all 3 directions; however, young female dancers demonstrated
      monotonic relationships in the AP direction only. In the dynamic measurements,
      both male and female dancers demonstrated monotonic relationships between head
      and lumbar movements for all parameters measured in the ML and vertical
      directions (p < .05). In conclusions, among female dancers static PB ability is
      correlated with their dynamic ability, whereas among male dancers, no
      relationship between the static and dynamic PB in the AP direction exists. Male
      dancers showed head and lumbar coordination in the static PB movement, but both
      genders manifested no head and lumbar coordination in the AP direction measured
      for dynamic PB.

PMID- 27715709
TI  - Acute effects of synthetic cannabinoids: Update 2015.
AB  - BACKGROUND: Cannabis is the most widely used illicit drug in the United States
      and Europe. In recent years, a range of new substances with cannabis-like effects
      known as synthetic cannabinoids (SCs)-have suddenly burst on the drug scene.
      However, there is limited information about the clinical hazards linked to the
      use of these emerging substances. This review summarizes the literature to date
      relating the health effects of SCs. METHOD: A systematic literature review of
      original case studies was performed using PubMed and Web of Science (January 1980
      July 2015). Only articles in which a drug screening was reported were included in
      this review. RESULTS: Forty-six articles meeting the inclusion criteria were
      included in this review, reporting data on 114 patients who went to hospital
      emergency departments after exposure to SCs. The majority of patients were
      adolescent or young adult males (14-25 years; 24.5 +/- 10.1 years). The most
      common route of administration was smoking. The SCs most involved were John
      William Huffman (JWH) derivatives, followed by XRL-11, ADB-PINACA, AM-2201, MAM
      2201, and 5F-PB-22. This analysis showed that the use of these substances may
      cause minor and moderate side effects similar to those of cannabis intoxication,
      including tachycardia, nausea, somnolence, hallucinations, paranoia, xerostomia,
      and injected conjunctivae among others. However, atypical cannabis intoxication
      effects and worse complications (such as renal injuries, aggressiveness, cerebral
      ischemia, myocardial infarction, etc.) were also observed, which led to a
      significant morbidity were also observed. Some SCs were highlighted as being
      involved in 24 cases of deaths. CONCLUSIONS: In this review, the nature and
      frequency of the signs and symptoms of SC poisoning were estimated in order to
      inform health professionals about the health risks of these new and emerging
      substances.

PMID- 27715710
TI  - System Justification's Opposite Effects on Psychological Well-Being: Testing a
      Moderated Mediation Model in a Gay Men and Lesbian Sample in Chile.
AB  - Those who adhere to system justifying beliefs benefit from a palliative function
      that buffers negative effects on psychological well-being. This has been
      consistently observed for high-status groups, whereas for members of low-status
      groups, it remains rather unclear whether system justification exerts a positive
      or a negative effect. This study tested the palliative effect of system
      justification on symptoms of anxiety-depression in a gay men and lesbian sample
      (N = 467) in Chile. Results from moderated mediation analyses revealed that
      system justification beliefs buffer symptoms of anxiety and depression. However,
      system justification enhances anxious and depressive symptoms through
      internalized homonegativity; this mediation effect was significant for gay men.
      We pose that justifying the social order comprises two contradictory functions:
      system justification as a coping source, and otherwise, as source of distress
      under conditions of in-group derogation, posing a threat to well-being among
      members of low-status groups (as observed in gay and lesbian individuals).
      Implications of the opposing effects, and gender differences are further
      discussed in this study.

PMID- 27715711
TI  - Strategies to Increase Cancer Detection: Review of True-Positive and False
      Negative Results at Digital Breast Tomosynthesis Screening.
AB  - Digital breast tomosynthesis (DBT) represents a valuable addition to breast
      cancer screening by decreasing recall rates while increasing cancer detection
      rates. The increased accuracy achieved with DBT is due to the quasi-three
      dimensional format of the reconstructed images and the ability to "scroll
      through" breast tissue in the reconstructed images, thereby reducing the effect
      of tissue superimposition found with conventional planar digital mammography. The
      margins of both benign and malignant lesions are more conspicuous at DBT, which
      allows improved lesion characterization, increased reader confidence, and
      improved screening outcomes. However, even with the improvements in accuracy
      achieved with DBT, there remain differences in breast cancer conspicuity by
      mammographic view. Early data suggest that breast cancers may be more conspicuous
      on craniocaudal (CC) views than on mediolateral oblique (MLO) views. While some
      very laterally located breast cancers may be visualized on only the MLO view, the
      increased conspicuity of cancers on the CC view compared with the MLO view
      suggests that DBT screening should be performed with two-view imaging. Even with
      the improved conspicuity of lesions at DBT, there may still be false-negative
      studies. Subtle lesions seen on only one view may be discounted, and dense and/or
      complex tissue patterns may make some cancers occult or extremely difficult to
      detect. Therefore, radiologists should be cognizant of both perceptual and
      cognitive errors to avoid potential pitfalls in lesion detection and
      characterization. (c)RSNA, 2016 Online supplemental material is available for
      this article.

PMID- 27715712
TI  - US of the Inguinal Canal: Comprehensive Review of Pathologic Processes with CT
      and MR Imaging Correlation.
AB  - Ultrasonography (US) has a fundamental role in the initial examination of
      patients who present with symptoms indicating abnormalities of the inguinal canal
      (IC), an area known for its complex anatomy. A thorough understanding of the
      embryologic and imaging characteristics of the contents of the IC is essential
      for any general radiologist. Moreover, an awareness of the various pathologic
      conditions that can affect IC structures is crucial to preventing misdiagnoses
      and ensuring optimal patient care. Early detection of IC abnormalities can reduce
      the risk of morbidity and mortality and facilitate proper treatment.
      Abnormalities may be related to increased intra-abdominal pressure, which can
      result in development of direct inguinal hernias and varicoceles, or to
      congenital anomalies of the processus vaginalis, which can result in development
      of indirect hernias and hydroceles. US is also helpful in assessing postoperative
      complications of hernia repair, such as hematoma, seroma, abscess, and hernia
      recurrence. In addition, it is often the modality initially used to detect
      neoplasms arising from or invading the IC. US is an important tool in the
      examination of patients suspected of having undescended testes or posttraumatic
      testicular retraction and is essential for the examination of patients suspected
      of having torsion or infectious inflammatory conditions of the spermatic cord.
      Online supplemental material is available for this article. (c)RSNA, 2016.

PMID- 27715713
TI  - Child and Interviewer Race in Forensic Interviewing.
AB  - The purpose of this study was to examine the potential effect of child race and
      interviewer race on forensic interviewing outcomes. The results of the regression
      analysis indicated that child race and interviewer race had a significant effect
      on interview outcome category (no findings, inconclusive, or findings consistent
      with sexual abuse). Furthermore, the results indicate that the interaction of
      child and interviewer race had predictive value for rates of findings consistent
      with sexual abuse but not in the direction predicted. Cross-race dyads had
      significantly higher rates of interview outcomes consistent with sexual abuse.
      These findings suggest that more research into the effect of race on disclosure
      of child sexual abuse is needed.

PMID- 27715714
TI  - Law enforcement attitudes towards naloxone following opioid overdose training.
AB  - BACKGROUND: Opioid intoxication and overdoses are life-threatening emergencies
      requiring rapid treatment. One response to this has been to train law enforcement
      to detect the signs of an opioid overdose and train them to administer naloxone
      to reverse the effects. Although not a new concept, few studies have attempted to
      examine this policy. METHODS: At 4 different locations in Indiana, law
      enforcement personnel were trained to detect the signs of an opioid-related
      overdose and how to administer naloxone to reverse the effects of the overdose.
      Pre and post surveys were administered at each location (N = 97). To examine
      changes in attitudes following training, the authors included items from the
      Opioid Overdose Attitudes Scale (OOAS), which measures respondents' competency,
      concerns, and readiness to administer naloxone. RESULTS: Among the full sample,
      naloxone training resulted in significant increases in competency, concerns, and
      readiness. Examining changes in attitudes by each location revealed that the
      training had the greatest effect on competency to administer naloxone and in
      easing concerns that law enforcement personal might have in administering
      naloxone. CONCLUSIONS: This study adds to others in showing that law enforcement
      personnel are receptive to naloxone training and that the OOAS is able to capture
      these attitudes. This study advances this literature by examining pre-post
      changes across multiple locations. As the distribution of naloxone continues to
      proliferate, this study and the OOAS may be valuable towards the development of
      an evidence-based training model for law enforcement.

PMID- 27715716
TI  - Pupil Diameter May Reflect Motor Control and Learning.
AB  - Non-luminance-mediated changes in pupil diameter have been used since the first
      studies by Darwin in 1872 as indicators of clinical, cognitive, and arousal
      states. However, the relation between processes involved in motor control and
      changes in pupil diameter remains largely unknown. Twenty participants attempted
      to compensate random walks of a cursor with a computer mouse to restrain its
      trajectory within a target circle while the authors recorded their pupil
      diameters. Two conditions allowed the authors to experimentally manipulate the
      motor and cognitive components of the task. First, the step size of the cursor's
      random walk was either large or small leading to 2 task difficulties (difficult
      or easy). Second, they instructed participants to imagine controlling the cursor
      by moving the mouse, but without actually moving it (task modality: imagined
      movement or real movement condition). Task difficulty and modality allowed the
      authors to show that pupil diameters reflect processes involved in motor control
      and in the processing of feedback, respectively. Furthermore, the authors also
      demonstrate that motor learning can be quantified by pupil size. This noninvasive
      approach provides a promising method for investigating not only motor control,
      but also motor imagery, a research field of growing importance in sports and
      rehabilitation.

PMID- 27715715
TI  - Comparison between active (pumped) and passive (diffusive) sampling methods for
      formaldehyde in pathology and histology laboratories.
AB  - This study was to determine occupational exposures to formaldehyde and to compare
      concentrations of formaldehyde obtained by active and passive sampling methods.
      In one pathology and one histology laboratories, exposure measurements were
      collected with sets of active air samplers (Supelco LpDNPH tubes) and passive
      badges (ChemDisk Aldehyde Monitor 571). Sixty-six sample pairs (49 personal and
      17 area) were collected and analyzed by NIOSH NMAM 2016 for active samples and
      OSHA Method 1007 (using the manufacturer's updated uptake rate) for passive
      samples. All active and passive 8-hr time-weighted average (TWA) measurements
      showed compliance with the OSHA permissible exposure limit (PEL-0.75 ppm) except
      for one passive measurement, whereas 78% for the active and 88% for the passive
      samples exceeded the NIOSH recommended exposure limit (REL-0.016 ppm). Overall,
      73% of the passive samples showed higher concentrations than the active samples
      and a statistical test indicated disagreement between two methods for all data
      and for data without outliers. The OSHA Method cautions that passive samplers
      should not be used for sampling situations involving formalin solutions because
      of low concentration estimates in the presence of reaction products of
      formaldehyde and methanol (a formalin additive). However, this situation was not
      observed, perhaps because the formalin solutions used in these laboratories
      included much less methanol (3%) than those tested in the OSHA Method (up to
      15%). The passive samplers in general overestimated concentrations compared to
      the active method, which is prudent for demonstrating compliance with an
      occupational exposure limit, but occasional large differences may be a result of
      collecting aerosolized droplets or splashes on the face of the samplers. In the
      situations examined in this study the passive sampler generally produces higher
      results than the active sampler so that a body of results from passive samplers
      demonstrating compliance with the OSHA PEL would be a valid conclusion. However,
      individual passive samples can show lower results than a paired active sampler so
      that a single result should be treated with caution.

PMID- 27715770
TI  - Introduction: Sexual Minorities' Discrimination in Iberian and Latin-American
      Countries.

PMID- 27715771
TI  - Surviving Violence in Everyday Life: A Communicative Approach to Homelessness.
AB  - In this narrative review, the author synthesizes the literature on homelessness
      across various disciplines (e.g., public health, social work, sociology, and
      communication) to demonstrate how the experiences of homelessness can be created,
      maintained, and reinforced through communication, including interpersonal
      interactions and public discourse. By conceptualizing homelessness as a
      culturally constructed and socially situated phenomenon, the author examines (a)
      the complex conceptualization of homelessness, (b) everyday violence faced by
      people who are homeless, and (c) coping strategies of people who are homeless. In
      summary, homelessness is a complex social phenomenon, involving tensions between
      individuals, families, and social systems, all of which are situated in the
      larger sociocultural and sociopolitical contexts of a specific time and place.

PMID- 27715830
TI  - Validation Study of the Revised Version of the Scale of Prejudice against Sexual
      and Gender Diversity in Brazil.
AB  - In Brazil, there is a deficit of culturally adapted tools to assess prejudice
      against sexual and gender diversity with empirically demonstrable validity and
      reliability. Prejudice against non-heterosexual orientations is a strong problem
      within Brazilian culture and is particularly related to non-normative expressions
      of gender. To address these issues, a scale was created. The objective of this
      article is to validate the revised version of this instrument developed for the
      specificities of Brazilian culture and establish its reliability. Eight thousand,
      one hundred and eighty-four undergraduate students from southern Brazil completed
      the revised version of Scale of Prejudice Against Sexual and Gender Diversity
      (PASGD). Analysis was conducted using Item Response Theory (IRT) model for rating
      scale data, criterion validity and confirmatory factor analysis (CFA). The scale
      showed good validity and reliability. The results indicate that the PASGD is a
      useful tool for assessing prejudice in the Brazilian context, adapted for the
      local Brazilian reality.

PMID- 27715772
TI  - Identity reconstruction among older cancer survivors: Age and meaning in the
      context of a life-altering illness.
AB  - This article evaluates how older cancer patients describe cancer survivorship and
      incorporate the cancer experience into long-term evaluations of health. From a
      series of 53 qualitative interviews with adults with histories of breast and
      prostate cancers and non-Hodgkin's lymphoma, we analyzed age-related discussions
      among those 65 and older (n = 21). Emergent themes revealed the: (1) historical
      conceptualization of cancer, (2) changed perspective following diagnosis, (3)
      cancer in the context of a long biography, (4) cancer in the context of the aging
      body and decline, and (5) meaning of time remaining and quality of life. One
      important suggestion from our work, relevant to all clinicians regardless of
      specialty or role, is to incorporate goals for the future into individualized
      survivor care plans for older survivors.

PMID- 27715903
TI  - Older women's negative psychological and physical experiences with injectable
      cosmetic treatments to the face.
AB  - Seven women (43 to 64 years old) who had negative or mixed emotions about having
      Botox and/or facial filler injections to the face to reduce signs of aging were
      interviewed about the impact of the procedures. Impacts ranged from
      disappointment to all-encompassing, lingering physical and psychological effects,
      and some women felt abandoned by the medical industrial complex when they turned
      to it for help with their symptoms. A feminist phenomenological analysis focused
      on corporeal, temporal, and relational existential modes of being. We describe
      their bodily experiences as (a) commodified, (b) fractured,

PMID- 27716015
TI  - Rotational vertebrobasilar insufficiency due to compression of a persistent first
      intersegmental vertebral artery variant: case report.
AB  - Rotational vertebrobasilar insufficiency, or bow hunter's syndrome, is a rare
      cause of posterior circulation ischemia, which, following rotation of the head,
      results in episodic vertigo, dizziness, nystagmus, or syncope. While typically
      caused by dynamic occlusion of the vertebral artery in its V2 and V3 segments,
      the authors here describe a patient with dynamic occlusion of the vertebral
      artery secondary to a persistent first intersegmental artery, a rare variant
      course of the vertebral artery. In this case the vertebral artery coursed under
      rather than over the posterior arch of the C-1. This patient was also found to
      have incomplete development of the posterior arch of C-1, as is often seen with
      this variant. The patient underwent dynamic digital subtraction angiography,
      which demonstrated occlusion at the variant vertebral artery with head turning.
      He was then taken for decompression of the vertebral artery through removal of
      the incomplete arch of C-1 that was causing the dynamic compression. After
      surgery the patient had a complete resolution of symptoms. In this report, the
      authors present the details of this case, describe the anatomical variants
      involved, and provide a discussion regarding the need for atlantoaxial fusion in
      these patients.

PMID- 27715904
TI  - Recent incarceration and buprenorphine maintenance treatment outcomes among human
      immunodeficiency virus-positive patients.
AB  - BACKGROUND: Opioid use disorder is a common cause of morbidity and mortality
      among people living with human immunodeficiency virus/acquired immunodeficiency
      syndrome (HIV/AIDS). Buprenorphine maintenance treatment (BMT) is an effective
      means of therapy, but patients with recent criminal justice involvement may need
      more support during BMT than other patients. The authors hypothesized that
      recently incarcerated BMT patients who initiated treatment in primary care would
      have poorer treatment outcomes than those who were not recently incarcerated.
      METHODS: Investigators analyzed data from a multisite cohort study of BMT
      integrated into HIV care. Patients were stratified by self-reported incarceration
      in the 30 days before initiation of BMT. The outcomes of interest were 6- and 12
      month treatment retention and self-reported opioid use. Investigators used
      multivariable logistic regression and hierarchical linear model, respectively, to
      evaluate the association between recent incarceration and these outcomes while
      adjusting for potential confounding variables. RESULTS: Among 305 BMT patients
      living with HIV/AIDS, 39 (13%) reported recent incarceration. Patients with
      recent incarceration (vs. without) were more likely to be homeless, unemployed,
      and previously diagnosed with mental illness. Recent incarceration was not
      significantly associated with differences in 6-month (odds ratio [OR] = 0.95; 95%
      confidence interval [CI] = 0.46-1.98) and 12-month (OR = 0.57; 95% CI = 0.27
      1.18) treatment retention or in self-reported opioid use (OR = 0.99; 95% CI =
      0.51-1.92) after adjustment for potential confounding variables. CONCLUSIONS:
      Those with incarceration in the 30 days prior to BMT initiation were more likely
      to be homeless, unemployed, and previously diagnosed with mental illness than
      those without recent incarceration. However, no significant difference in self
      reported opioid use or 6-month or 12-month retention in treatment was detected
      between those with and without recent incarceration. Future studies should
      confirm these findings with larger sample sizes. Encouraging formerly
      incarcerated individuals with opioid use disorder to initiate evidence-based
      treatments, including BMT, should be part of efforts to confront the opioid
      addiction epidemic in the United States.

PMID- 27716016
TI  - Posterior corrective surgery with a multilevel transforaminal lumbar interbody
      fusion and a rod rotation maneuver for patients with degenerative lumbar
      kyphoscoliosis.
AB  - The purpose of this study was to assess the clinical results of posterior
      corrective surgery using a multilevel transforaminal lumbar interbody fusion
      (TLIF) with a rod rotation (RR) and to evaluate the segmental corrective effect
      of a TLIF using CT imaging. The medical records of 15 consecutive patients with
      degenerative lumbar kyphoscoliosis (DLKS) who had undergone posterior spinal
      corrective surgery using a multilevel TLIF with an RR technique and who had a
      minimum follow-up of 2 years were retrospectively reviewed. Radiographic
      parameters were evaluated using plain radiographs, and segmental correction was
      evaluated using CT imaging. Clinical outcomes were evaluated with the Scoliosis
      Research Society Patient Questionnaire-22 (SRS-22) and the SF-36. The mean follow
      up period was 46.7 months, and the mean age at the time of surgery was 60.7
      years. The mean total SRS-22 score was 2.9 before surgery and significantly
      improved to 4.0 at the latest follow-up. The physical functioning, role
      functioning (physical), and social functioning subcategories of the SF-36 were
      generally improved at the latest follow-up, although the changes in these scores
      were not statistically significant. The bodily pain, vitality, and mental health
      subcategories were significantly improved at the latest follow-up (p < 0.05).
      Three complications occurred in 3 patients (20%). The Cobb angle of the lumbar
      curve was reduced to 20.3 degrees  after surgery. The overall correction rate was
      66.4%. The pelvic incidence-lumbar lordosis (preoperative/postoperative = 31.5
      degrees /4.3 degrees ), pelvic tilt (29.2 degrees /18.9 degrees ), and sagittal
      vertical axis (78.3/27.6 mm) were improved after surgery and remained so
      throughout the follow-up. Computed tomography image analysis suggested that a 1
      level TLIF can result in 10.9 degrees  of scoliosis correction and 6.8 degrees 
      of lordosis. Posterior corrective surgery using a multilevel TLIF with an RR on
      patients with DLKS can provide effective correction in the coronal plane but
      allows only limited sagittal correction.

PMID- 27716017
TI  - Reconstruction of the C-1 lateral mass with a titanium expandable cage after
      resection of eosinophilic granuloma in an adult patient.
AB  - Spinal involvement occurs frequently in cases of eosinophilic granuloma (EG), but
      surgical treatment is limited primarily to those with spinal instability.
      Involvement of the cervical spine is rare, but primarily occurs in the vertebral
      bodies, and is normally amenable to anterior corpectomy and spinal
      reconstruction. The authors describe a 27-year-old man with pathologically proven
      EG who presented with complete destruction of the C-1 lateral mass requiring
      spinal stabilization. A titanium expandable cage was used to reconstruct the
      weight-bearing column from the occipital condyle to the superior articular
      surface of C-2 from a posterior approach, with preservation of the traversing
      vertebral artery. To the authors' knowledge, this is the first reported instance
      of reconstruction of the C-1 lateral mass using an expandable metal cage, which
      facilitated preservation of the vertebral artery.

PMID- 27716018
TI  - Less invasive lumbopelvic fixation technique using a percutaneous pedicle screw
      system for unstable pelvic ring fracture in a patient with severe multiple
      traumas.
AB  - Pelvic ring fractures are defined as life-threatening injuries that can be
      treated surgically with external or internal fixation. The authors report on an
      81-year-old woman with an unstable pelvic fracture accompanying multiple traumas
      that was successfully treated with a less invasive procedure. The patient was
      injured in a traffic accident and sustained a total of 20 fractures, including
      pelvic ring, bilateral rib, and lumbar transverse processes fractures, and
      multiple fractures of both upper and lower extremities. The pelvic ring fracture
      was unstable with fractures of the bilateral sacrum with right sacroiliac
      disruption, right superior and inferior pubic rami, left superior pubic ramus,
      and ischium. During emergency surgery, bilateral external fixation was applied to
      the iliac crest to stabilize the pelvic ring. Second and third surgeries were
      performed 11 and 18 days after the first emergency surgery, respectively, to
      treat the multiple fractures. At the third surgery, the pelvic ring fracture was
      stabilized surgically using a less invasive posterior fixation technique. In this
      technique, 2 iliac screws were inserted on each side following an 8-cm midline
      posterior incision from the S-1 to S-3 spinous process, with the subcutaneous
      tissue detached from the fascia of the paraspinal muscles. The S-2 spinous
      process was removed and 2 rods were connected to bilateral iliac screws to
      stabilize the bilateral ilium in a switchback fashion. A crosslink device was
      applied to connect the 2 rods at the base of the S-2 spinous process. Following
      pelvic fixation, percutaneous pedicle screws were inserted into L-4 and L-5
      vertebral bodies on both sides, and connected to the cranial rod connecting the
      bilateral iliac screws, thus completing the lumbopelvic fixation. The
      postoperative course was favorable with no postoperative complications. At the 10
      month follow-up, bone union had been achieved at the superior ramus of the pubis,
      the patient did not complain of pain, and her activities of daily life returned
      to preinjury status. Unstable pelvic ring fractures need to be sufficiently
      stabilized for good surgical outcome. However, to avoid postoperative
      complications, a less invasive treatment is preferred, particularly in cases with
      poor general condition. This procedure is less invasive and provides sufficient
      stabilization to the unstable pelvic ring fracture, and thus is the ideal
      surgical procedure for such cases.

PMID- 27716019
TI  - Going solo: Findings from a survey of women aging without a partner and who do
      not have children.
AB  - Greater longevity in the UK population has led to the increasing diversity of
      women experiencing aging in a multitude of ways. Internationally, gender
      inequalities in aging are still relatively invisible within both government
      policy and everyday life for particular groups of women. This article explores
      the concept of women growing older "solo"-by which we mean women who find
      themselves nonpartnered and aging without children as they move into later life.
      We report on the findings from a mixed-methods survey of 76 solo women in the UK
      aged 50 years and over, used to provide a broader overview of the issues and
      challenges they face as they move into later life. Qualitative data from the
      survey captured respondents' perspectives about the links between their
      relationships status and well-being in later life and highlighted specific
      cumulative disadvantages emerging for some women as a result of their solo
      lifestyles. We discuss two key themes that were identified, "solo-loneliness" and
      "meaningful futures," in conjunction with the relevant literature and make
      suggestions for future research within gender and aging studies that could
      enhance more positive approaches to solo lifestyles.

PMID- 27716020
TI  - At the threshold of retirement: From all-absorbing relations to self
      actualization.
AB  - To investigate the complexities of the retirement process, the present article
      draws on a case study of Eva, a Swedish woman who "awakened" from all-absorbing
      relations. It considers the ways in which retirement can enable liberation from
      patriarchal kinship structures and embodied values of respectability. The aim is
      to illuminate how deep, embodied values can become conscious and explicit during
      precarious life situations and transitional phases. The relation between the
      Swedish welfare state, an I-we balance, and gender equity values are illuminated.
      These analytical dimensions support the analysis by providing insights into the
      ways in which individuals embody and use cultural and social structures when they
      aim to manage unpredictability and to create change toward self-actualization.

PMID- 27716021
TI  - The experience of high-frequency gambling behavior of older adult females in the
      United Kingdom: An interpretative phenomenological analysis.
AB  - The prevalence of older adult female gambling participation and gambling disorder
      is increasing in the UK, and there is a paucity of published research available
      to understand possible risk factors for frequent gambling in this demographic.
      The aim of the current study was to identify and explore motivations and patterns
      of gambling behavior in high-frequency older adult female gamblers in the UK,
      from the perspective of the individual and in the context of their experience of
      aging. Ten UK older adult female high-frequency gamblers were recruited via
      stratified purposive sampling, with a mean age of 70.4 years. Data was collected
      via semistructured interviews and analyzed using interpretative phenomenological
      analysis. Three core themes representative of the experience of this phenomenon
      emerged from the transcripts, including: Filling voids, emotional escape, and
      overspending. The present study has provided a contextualized understanding of
      motivating factors and several age-related vulnerabilities that may account for
      high gambling frequency in this population.

PMID- 27716022
TI  - Identification of selective sweeps reveals divergent selection between Chinese
      Holstein and Simmental cattle populations.
AB  - BACKGROUND: The identification of signals left by recent positive selection
      provides a feasible approach for targeting genomic variants that underlie complex
      traits and fitness. A better understanding of the selection mechanisms that
      occurred during the evolution of species can also be gained. In this study, we
      simultaneously detected the genome-wide footprints of recent positive selection
      that occurred within and between Chinese Holstein and Simmental populations,
      which have been subjected to artificial selection for distinct purposes. We
      conducted analyses using various complementary approaches, including LRH, XP-EHH
      and FST, based on the Illumina 770K high-density single nucleotide polymorphism
      (SNP) array, to enable more comprehensive detection. RESULTS: We successfully
      constructed profiles of selective signals in both cattle populations. To further
      annotate these regions, we identified a set of novel functional genes related to
      growth, reproduction, immune response and milk production. There were no
      overlapping candidate windows between the two breeds. Finally, we investigated
      the distribution of SNPs that had low FST values across five distinct functional
      regions in the genome. In the low-minor allele frequency bin, we found a higher
      proportion of low-FST SNPs in the exons of the bovine genome, which indicates
      strong purifying selection of the exons. CONCLUSIONS: The selection signatures
      identified in these two populations demonstrated positive selection pressure on a
      set of important genes with potential functions that are involved in many
      biological processes. We also demonstrated that in the bovine genome, exons were
      under strong purifying selection. Our findings provide insight into the
      mechanisms of artificial selection and will facilitate follow-up functional
      studies of potential candidate genes that are related to various economically
      important traits in cattle.

PMID- 27716024
TI  - Genetic composition of captive panda population.
AB  - BACKGROUND: A major function of the captive panda population is to preserve the
      genetic diversity of wild panda populations in their natural habitats.
      Understanding the genetic composition of the captive panda population in terms of
      genetic contributions from the wild panda populations provides necessary
      knowledge for breeding plans to preserve the genetic diversity of the wild panda
      populations. RESULTS: The genetic contributions from different wild populations
      to the captive panda population were highly unbalanced, with Qionglai accounting
      for 52.2 % of the captive panda gene pool, followed by Minshan with 21.5 %,
      Qinling with 10.6 %, Liangshan with 8.2 %, and Xiaoxiangling with 3.6 %, whereas
      Daxiangling, which had similar population size as Xiaoxiangling, had no genetic
      representation in the captive population. The current breeding recommendations
      may increase the contribution of some small wild populations at the expense of
      decreasing the contributions of other small wild populations, i.e., increasing
      the Xiaoxiangling contribution while decreasing the contribution of Liangshan, or
      sharply increasing the Qinling contribution while decreasing the contributions of
      Xiaoxiangling and Liangshan, which were two of the three smallest wild
      populations and were already severely under-represented in the captive
      population. We developed three habitat-controlled breeding plans that could
      increase the genetic contributions from the smallest wild populations to 6.7-11.2
      % for Xiaoxiangling, 11.5-12.3 % for Liangshan and 12.9-20.0 % for Qinling among
      the offspring of one breeding season while reducing the risk of hidden inbreeding
      due to related founders from the same habitat undetectable by pedigree data.
      CONCLUSION: The three smallest wild panda populations of Daxiangling,
      Xiaoxiangling and Liangshan either had no representation or were severely
      unrepresented in the current captive panda population. By incorporating the
      breeding goal of increasing the genetic contributions from the smallest wild
      populations into breeding plans, the severely under-represented small wild
      populations in the current captive panda population could be increased steadily
      for the near future.

PMID- 27716023
TI  - Identification of replication-dependent and replication-independent linker
      histone complexes: Tpr specifically promotes replication-dependent linker histone
      stability.
AB  - BACKGROUND: There are 11 variants of linker histone H1 in mammalian cells. Beyond
      their shared abilities to stabilize and condense chromatin, the H1 variants have
      been found to have non-redundant functions, the mechanisms of which are not fully
      understood. Like core histones, there are both replication-dependent and
      replication-independent linker histone variants. The histone chaperones and other
      factors that regulate linker histone dynamics in the cell are largely unknown. In
      particular, it is not known whether replication-dependent and replication
      independent linker histones interact with distinct or common sets of proteins. To
      better understand linker histone dynamics and assembly, we used chromatography
      and mass spectrometry approaches to identify proteins that are associated with
      replication-dependent and replication-independent H1 variants. We then used a
      variety of in vivo analyses to validate the functional relevance of identified
      interactions. RESULTS: We identified proteins that bind to all linker histone
      variants and proteins that are specific for only one class of variant. The
      factors identified include histone chaperones, transcriptional regulators, RNA
      binding proteins and ribosomal proteins. The nuclear pore complex protein Tpr,
      which was found to associate with only replication-dependent linker histones,
      specifically promoted their stability. CONCLUSION: Replication-dependent and
      replication-independent linker histone variants can interact with both common and
      distinct sets of proteins. Some of these factors are likely to function as
      histone chaperones while others may suggest novel links between linker histones
      and RNA metabolism. The nuclear pore complex protein Tpr specifically interacts
      with histone H1.1 and H1.2 but not H1x and can regulate the stability of these
      replication-dependent linker histones.

PMID- 27716025
TI  - On the role of the proventricle region in reproduction and regeneration in
      Typosyllis antoni (Annelida: Syllidae).
AB  - BACKGROUND: Syllids are a species rich annelid family possessing remarkable
      regenerative ability, which is not only the response after traumatic injury, but
      also a key step during the life cycle of several syllid taxa. In these animals
      the posterior part of the body becomes an epitoke and is later detached as a
      distinct unit named stolon. Such a sexual reproductive mode is named schizogamy
      or stolonization. The prostomium and the proventricle, a modified foregut
      structure, have been proposed to have a control function during this process,
      though the concrete mechanisms behind it have never been elucidated. RESULTS: By
      using different experimental set-ups, histology and immunohistochemistry combined
      with subsequent cLSM analyzes, we investigate and document the regeneration and
      stolonization in specimens of Typosyllis antoni that were amputated at different
      levels throughout the antero-posterior body axis. The removal of the anterior end
      including the proventricle implies an incomplete anterior regeneration as well as
      severe deviations from the usual reproductive pattern, i.e. accelerated
      stolonization, masculinization and the occurrence of aberrant stolons. The
      detailed anatomy of aberrant stolons is described. A histological study of the
      proventricle revealed no signs of glandular or secretory structures. The
      ventricle and the caeca are composed of glandular tissue but they are not
      involved in the reproductive and regenerative processes. CONCLUSIONS: As in other
      investigated syllids, the proventricle region has a significant role during
      stolonization and reproduction processes in Typosyllis antoni. When the
      proventricle region is absent, anterior and posterior regeneration are
      considerably deviated from the general patterns. However, proventricle
      ultrastructure does not show any glandular component, thereby questioning a
      direct involvement of this organ itself in the control of reproduction and
      regeneration. Our findings offer a comprehensive starting point for further
      studies of regeneration and reproductive control in syllids as well as annelids
      in general.

PMID- 27716026
TI  - Arginine deiminase pathway enzymes: evolutionary history in metamonads and other
      eukaryotes.
AB  - BACKGROUND: Multiple prokaryotic lineages use the arginine deiminase (ADI)
      pathway for anaerobic energy production by arginine degradation. The distribution
      of this pathway among eukaryotes has been thought to be very limited, with only
      two specialized groups living in low oxygen environments (Parabasalia and
      Diplomonadida) known to possess the complete set of all three enzymes. We have
      performed an extensive survey of available sequence data in order to map the
      distribution of these enzymes among eukaryotes and to reconstruct their
      phylogenies. RESULTS: We have found genes for the complete pathway in almost all
      examined representatives of Metamonada, the anaerobic protist group that includes
      parabasalids and diplomonads. Phylogenetic analyses indicate the presence of the
      complete pathway in the last common ancestor of metamonads and heterologous
      transformation experiments suggest its cytosolic localization in the metamonad
      ancestor. Outside Metamonada, the complete pathway occurs rarely, nevertheless,
      it was found in representatives of most major eukaryotic clades. CONCLUSIONS:
      Phylogenetic relationships of complete pathways are consistent with the presence
      of the Archaea-derived ADI pathway in the last common ancestor of all eukaryotes,
      although other evolutionary scenarios remain possible. The presence of the
      incomplete set of enzymes is relatively common among eukaryotes and it may be
      related to the fact that these enzymes are involved in other cellular processes,
      such as the ornithine-urea cycle. Single protein phylogenies suggest that the
      evolutionary history of all three enzymes has been shaped by frequent gene losses
      and horizontal transfers, which may sometimes be connected with their diverse
      roles in cellular metabolism.

PMID- 27716027
TI  - Identification of gene-drug interactions that impact patient survival in TCGA.
AB  - BACKGROUND: With the advent of large scale biological data collection for various
      diseases, data analysis pipelines and workflows need to be established to build
      frameworks for integrative analysis. Here the authors present a pipeline for
      identifying disease specific gene-drug interactions using CNV (Copy Number
      Variation) and clinical data from the TCGA (The Cancer Genome Atlas) project. Two
      cancer types were selected for analysis, LGG (Brain lower grade glioma) and GBM
      (Glioblastoma multiforme), due to the possible progression from LGG to GBM in
      some cases. The copy number and clinical data were then used to preform survival
      analysis on a gene by gene basis on sub-populations of patients exposed to a
      given drug. RESULTS: Several gene-drug interactions are identified, where the
      copy number of a gene is associated to survival of a patient exposed to a certain
      drug. Both Irinotecan/HAS2 (Hyaluronan synthase 2) and Bevacizumab/PGAM1
      (Phosphoglycerate mutase 1) are interactions found in this study with independent
      confirmation. Independent work in colon, breast cancer and leukemia (Gyorffy,
      Breast Cancer Res Treat 123:725-731, 2010; Mueller, Mol Cancer Ther 11:3024-3032,
      2010; Hitosugi, Cancer Cell 13:585-600, 2012) showed these two interactions can
      lead to increased survival. CONCLUSION: While the pipeline produced several
      possible interactions where increased survival is linked to normal or increased
      copy number of a given gene for patients treated with a given drug, no instance
      of low copy number or full deletion was linked to increased survival. The
      development of this pipeline shows a promising utility to identify possible
      beneficial gene-drug interactions that could improve patient survival and may
      illustrate some of the problems inherent in this kind of analysis on these data.

PMID- 27716029
TI  - Simulating cryo electron tomograms of crowded cell cytoplasm for assessment of
      automated particle picking.
AB  - BACKGROUND: Cryo-electron tomography is an important tool to study structures of
      macromolecular complexes in close to native states. A whole cell cryo electron
      tomogram contains structural information of all its macromolecular complexes.
      However, extracting this information remains challenging, and relies on
      sophisticated image processing, in particular for template-free particle
      extraction, classification and averaging. To develop these methods it is crucial
      to realistically simulate tomograms of crowded cellular environments, which can
      then serve as ground truth models for assessing and optimizing methods for
      detection of complexes in cell tomograms. RESULTS: We present a framework to
      generate crowded mixtures of macromolecular complexes for realistically
      simulating cryo electron tomograms including noise and image distortions due to
      the missing-wedge effects. Simulated tomograms are then used for assessing the
      template-free Difference-of-Gaussian (DoG) particle-picking method to detect
      complexes of different shapes and sizes under various crowding and noise levels.
      We identified DoG parameter settings that maximize precision and recall for
      detecting particles over a wide range of sizes and shapes. We observed that
      medium sized DoG scaling factors showed the overall best performance. To further
      improve performance, we propose a combination strategy for integrating results
      from multiple parameter settings. With increasing macromolecular crowding levels,
      the precision of particle picking remained relatively high, while the recall was
      dramatically reduced, which limits the detection of sufficient copy numbers of
      complexes in a crowded environment. Over a wide range of increasing noise levels,
      the DoG particle picking performance remained stable, but dramatically reduced
      beyond a specific noise threshold. CONCLUSIONS: Automatic and reference-free
      particle picking is an important first step in a visual proteomics analysis of
      cell tomograms. However, cell cytoplasm is highly crowded, which makes particle
      detection challenging. It is therefore important to test particle-picking methods
      in a realistic crowded setting. Here, we present a framework for simulating
      tomograms of cellular environments at high crowding levels and assess the DoG
      particle picking method. We determined optimal parameter settings to maximize the
      performance of the DoG particle-picking method.

PMID- 27716028
TI  - Genetic signals of high-altitude adaptation in amphibians: a comparative
      transcriptome analysis.
AB  - BACKGROUND: High-altitude adaptation provides an excellent system for studying
      how organisms cope with multiple environmental stressors and interacting genetic
      modifications. To explore the genetic basis of high-altitude adaptation in
      poikilothermic animals, we acquired transcriptome sequences from a high-altitude
      population and a low-altitude population of the Asiatic toad (Bufo gargarizans).
      Transcriptome data from another high-altitude amphibian, Rana kukunoris and its
      low-altitude relative R. chensiensis, which are from a previous study, were also
      incorporated into our comparative analysis. RESULTS: More than 40,000 transcripts
      were obtained from each transcriptome, and 5107 one-to-one orthologs were
      identified among the four taxa for comparative analysis. A total of 29 (Bufo) and
      33 (Rana) putative positively selected genes were identified for the two high
      altitude species, which were mainly concentrated in nutrient metabolism related
      functions. Using SNP-tagging and FST outlier analysis, we further tested 89 other
      nutrient metabolism related genes for signatures of natural selection, and found
      that two genes, CAPN2 and ITPR1, were likely under balancing selection. We did
      not detect any positively selected genes associated with response to hypoxia.
      CONCLUSIONS: Amphibians clearly employ different genetic mechanisms for high
      altitude adaptation compared to endotherms. Modifications of genes associated
      with nutrient metabolism feature prominently while genes related to hypoxia
      tolerance appear to be insignificant. Poikilotherms represent the majority of
      animal diversity, and we hope that our results will provide useful directions for
      future studies of amphibians as well as other poikilotherms.

PMID- 27716030
TI  - Handling missing rows in multi-omics data integration: multiple imputation in
      multiple factor analysis framework.
AB  - BACKGROUND: In omics data integration studies, it is common, for a variety of
      reasons, for some individuals to not be present in all data tables. Missing row
      values are challenging to deal with because most statistical methods cannot be
      directly applied to incomplete datasets. To overcome this issue, we propose a
      multiple imputation (MI) approach in a multivariate framework. In this study, we
      focus on multiple factor analysis (MFA) as a tool to compare and integrate
      multiple layers of information. MI involves filling the missing rows with
      plausible values, resulting in M completed datasets. MFA is then applied to each
      completed dataset to produce M different configurations (the matrices of
      coordinates of individuals). Finally, the M configurations are combined to yield
      a single consensus solution. RESULTS: We assessed the performance of our method,
      named MI-MFA, on two real omics datasets. Incomplete artificial datasets with
      different patterns of missingness were created from these data. The MI-MFA
      results were compared with two other approaches i.e., regularized iterative MFA
      (RI-MFA) and mean variable imputation (MVI-MFA). For each configuration resulting
      from these three strategies, the suitability of the solution was determined
      against the true MFA configuration obtained from the original data and a
      comprehensive graphical comparison showing how the MI-, RI- or MVI-MFA
      configurations diverge from the true configuration was produced. Two approaches
      i.e., confidence ellipses and convex hulls, to visualize and assess the
      uncertainty due to missing values were also described. We showed how the areas of
      ellipses and convex hulls increased with the number of missing individuals. A
      free and easy-to-use code was proposed to implement the MI-MFA method in the R
      statistical environment. CONCLUSIONS: We believe that MI-MFA provides a useful
      and attractive method for estimating the coordinates of individuals on the first
      MFA components despite missing rows. MI-MFA configurations were close to the true
      configuration even when many individuals were missing in several data tables.
      This method takes into account the uncertainty of MI-MFA configurations induced
      by the missing rows, thereby allowing the reliability of the results to be
      evaluated.

PMID- 27716031
TI  - Boolean regulatory network reconstruction using literature based knowledge with a
      genetic algorithm optimization method.
AB  - BACKGROUND: Prior knowledge networks (PKNs) provide a framework for the
      development of computational biological models, including Boolean models of
      regulatory networks which are the focus of this work. PKNs are created by a
      painstaking process of literature curation, and generally describe all relevant
      regulatory interactions identified using a variety of experimental conditions and
      systems, such as specific cell types or tissues. Certain of these regulatory
      interactions may not occur in all biological contexts of interest, and their
      presence may dramatically change the dynamical behaviour of the resulting
      computational model, hindering the elucidation of the underlying mechanisms and
      reducing the usefulness of model predictions. Methods are therefore required to
      generate optimized contextual network models from generic PKNs. RESULTS: We
      developed a new approach to generate and optimize Boolean networks, based on a
      given PKN. Using a genetic algorithm, a model network is built as a sub-network
      of the PKN and trained against experimental data to reproduce the experimentally
      observed behaviour in terms of attractors and the transitions that occur between
      them under specific perturbations. The resulting model network is therefore
      contextualized to the experimental conditions and constitutes a dynamical Boolean
      model closer to the observed biological process used to train the model than the
      original PKN. Such a model can then be interrogated to simulate response under
      perturbation, to detect stable states and their properties, to get insights into
      the underlying mechanisms and to generate new testable hypotheses. CONCLUSIONS:
      Generic PKNs attempt to synthesize knowledge of all interactions occurring in a
      biological process of interest, irrespective of the specific biological context.
      This limits their usefulness as a basis for the development of context-specific,
      predictive dynamical Boolean models. The optimization method presented in this
      article produces specific, contextualized models from generic PKNs. These
      contextualized models have improved utility for hypothesis generation and
      experimental design. The general applicability of this methodological approach
      makes it suitable for a variety of biological systems and of general interest for
      biological and medical research. Our method was implemented in the software
      optimusqual, available online at http://www.vital-it.ch/software/optimusqual/ .

PMID- 27716032
TI  - Expressed alleles of imprinted IGF2, DLK1 and MEG3 colocalize in 3D-preserved
      nuclei of porcine fetal cells.
AB  - BACKGROUND: To explore the relationship between spatial genome organization and
      gene expression in the interphase nucleus, we used a genomic imprinting model,
      which offers parental-specific gene expression. Using 3D FISH in porcine fetal
      liver cells, we compared the nuclear organization of the two parental alleles
      (expressed or not) of insulin-like growth factor 2 (IGF2), a paternally imprinted
      gene located on chromosome 2. We investigated whether its nuclear positioning
      favors specific locus associations. We also tested whether IGF2 is implicated in
      long-range chromatin trans-associations as previously shown in the mouse model
      species for its reciprocal imprinted gene H19. RESULTS: We focused on the 3D
      position of IGF2 alleles, with respect to their individual chromosome 2
      territories. The paternally expressed allele was tagged with nascent RNA. There
      were no significant differences in the position of the two alleles (p = 0.06). To
      determine long-range chromatin trans-interactions, we chose 12 genes, some of
      which are known to be imprinted in mammalian model species and belong to a
      network of imprinted genes (i.e. SLC38A4, DLK1, MEG3, and ZAC1). We screened them
      and ABCG2, OSBP2, OSBPL1, RPL32, NF1, ZAR1, SEP15, GPC3 for associations with
      IGF2 in liver cells. All imprinted genes tested showed an association with IGF2.
      The DLK1/MEG3 locus showed the highest rate of colocalization. This gene
      association was confirmed by 3D FISH (in 20 % of the nuclei analyzed), revealing
      also the close proximity of chromosomes 2 and 7 (in 60 % of nuclei). Furthermore,
      our observations showed that the expressed paternal IGF2 allele is involved in
      this association. This IGF2-(DLK1/MEG3) association also occurred in a high
      percentage of fetal muscle cells (36 % of nuclei). Finally, we showed that
      nascent IGF2, DLK1 and MEG3 RNAs can associate in pairs or in a three-way
      combination. CONCLUSION: Our results show that trans-associations occur between
      three imprinted genes IGF2, DLK1 and MEG3 both in fetal liver and muscle cells.
      All three expressed alleles associated in muscle cells. Our findings suggest that
      the 3D nuclear organization is linked to the transcriptional state of these
      genes.

PMID- 27716034
TI  - VennDiagramWeb: a web application for the generation of highly customizable Venn
      and Euler diagrams.
AB  - BACKGROUND: Visualization of data generated by high-throughput, high
      dimensionality experiments is rapidly becoming a rate-limiting step in
      computational biology. There is an ongoing need to quickly develop high-quality
      visualizations that can be easily customized or incorporated into automated
      pipelines. This often requires an interface for manual plot modification, rapid
      cycles of tweaking visualization parameters, and the generation of graphics code.
      To facilitate this process for the generation of highly-customizable, high
      resolution Venn and Euler diagrams, we introduce VennDiagramWeb: a web
      application for the widely used VennDiagram R package. VennDiagramWeb is hosted
      at http://venndiagram.res.oicr.on.ca/ . RESULTS: VennDiagramWeb allows real-time
      modification of Venn and Euler diagrams, with parameter setting through a web
      interface and immediate visualization of results. It allows customization of
      essentially all aspects of figures, but also supports integration into
      computational pipelines via download of R code. Users can upload data and
      download figures in a range of formats, and there is exhaustive support
      documentation. CONCLUSIONS: VennDiagramWeb allows the easy creation of Venn and
      Euler diagrams for computational biologists, and indeed many other fields. Its
      ability to support real-time graphics changes that are linked to downloadable
      code that can be integrated into automated pipelines will greatly facilitate the
      improved visualization of complex datasets. For application support please
      contact Paul.Boutros@oicr.on.ca.

PMID- 27716033
TI  - Adrenal cortex expression quantitative trait loci in a German Holstein *
      Charolais cross.
AB  - BACKGROUND: The importance of the adrenal gland in regard to lactation and
      reproduction in cattle has been recognized early. Caused by interest in animal
      welfare and the impact of stress on economically important traits in farm animals
      the adrenal gland and its function within the stress response is of increasing
      interest. However, the molecular mechanisms and pathways involved in stress
      related effects on economically important traits in farm animals are not fully
      understood. Gene expression is an important mechanism underlying complex traits,
      and genetic variants affecting the transcript abundance are thought to influence
      the manifestation of an expressed phenotype. We therefore investigated the
      genetic background of adrenocortical gene expression by applying an adaptive
      linear rank test to identify genome-wide expression quantitative trait loci
      (eQTL) for adrenal cortex transcripts in cattle. RESULTS: A total of 10,986
      adrenal cortex transcripts and 37,204 single nucleotide polymorphisms (SNPs) were
      analysed in 145 F2 cows of a Charolais * German Holstein cross. We identified 505
      SNPs that were associated with the abundance of 129 transcripts, comprising 482
      cis effects and 17 trans effects. These SNPs were located on all chromosomes but
      X, 16, 24 and 28. Associated genes are mainly involved in molecular and cellular
      functions comprising free radical scavenging, cellular compromise, cell
      morphology and lipid metabolism, including genes such as CYP27A1 and LHCGR that
      have been shown to affect economically important traits in cattle. CONCLUSIONS:
      In this study we showed that adrenocortical eQTL affect the expression of genes
      known to contribute to the phenotypic manifestation in cattle. Furthermore, some
      of the identified genes and related molecular pathways were previously shown to
      contribute to the phenotypic variation of behaviour, temperament and growth at
      the onset of puberty in the same population investigated here. We conclude that
      eQTL analysis appears to be a useful approach providing insight into the
      molecular and genetic background of complex traits in cattle and will help to
      understand molecular networks involved.

PMID- 27716036
TI  - Identification of large disjoint motifs in biological networks.
AB  - BACKGROUND: Biological networks provide great potential to understand how cells
      function. Network motifs, frequent topological patterns, are key structures
      through which biological networks operate. Finding motifs in biological networks
      remains to be computationally challenging task as the size of the motif and the
      underlying network grow. Often, different copies of a given motif topology in a
      network share nodes or edges. Counting such overlapping copies introduces
      significant problems in motif identification. RESULTS: In this paper, we develop
      a scalable algorithm for finding network motifs. Unlike most of the existing
      studies, our algorithm counts independent copies of each motif topology. We
      introduce a set of small patterns and prove that we can construct any larger
      pattern by joining those patterns iteratively. By iteratively joining already
      identified motifs with those patterns, our algorithm avoids (i) constructing
      topologies which do not exist in the target network (ii) repeatedly counting the
      frequency of the motifs generated in subsequent iterations. Our experiments on
      real and synthetic networks demonstrate that our method is significantly faster
      and more accurate than the existing methods including SUBDUE and FSG.
      CONCLUSIONS: We conclude that our method for finding network motifs is scalable
      and computationally feasible for large motif sizes and a broad range of networks
      with different sizes and densities. We proved that any motif with four or more
      edges can be constructed as a join of the small patterns.

PMID- 27716035
TI  - Molecular evolution of Odorant-binding proteins gene family in two closely
      related Anastrepha fruit flies.
AB  - BACKGROUND: Odorant-binding proteins (OBPs) are of great importance for survival
      and reproduction since they participate in initial steps of the olfactory signal
      transduction cascade, solubilizing and transporting chemical signals to the
      olfactory receptors. A comparative analysis of OBPs between closely related
      species may help explain how these genes evolve and are maintained under natural
      selection and how differences in these proteins can affect olfactory responses.
      We studied OBP genes in the closely related species Anastrepha fraterculus and A.
      obliqua, which have different host preferences, using data from RNA-seq cDNA
      libraries of head and reproductive tissues from male and female adults, aiming to
      understand the speciation process occurred between them. RESULTS: We identified
      23 different OBP sequences from Anastrepha fraterculus and 24 from A. obliqua,
      which correspond to 20 Drosophila melanogaster OBP genes. Phylogenetic analysis
      separated Anastrepha OBPs sequences in four branches that represent four
      subfamilies: classic, minus-C, plus-C and dimer. Both species showed five plus-C
      members, which is the biggest number found in tephritids until now. We found
      evidence of positive selection in four genes and at least one duplication event
      that preceded the speciation of these two species. Inferences on tertiary
      structures of putative proteins from these genes revealed that at least one
      positively selected change involves the binding cavity (the odorant binding
      region) in the plus-C OBP50a. CONCLUSIONS: A. fraterculus and A. obliqua have a
      bigger OBP repertoire than the other tephritids studied, though the total number
      of Anastrepha OBPs may be larger, since we studied only a limited number of
      tissues. The contrast of these closely related species reveals that there are
      several amino acid changes between the homologous genes, which might be related
      to their host preferences. The plus-C OBP that has one amino acid under positive
      selection located in the binding cavity may be under a selection pressure to
      recognize and bind a new odorant. The other positively selected sites found may
      be involved in important structural and functional changes, especially ones in
      which site-specific changes would radically change amino acid properties.

PMID- 27716037
TI  - Impact of post-alignment processing in variant discovery from whole exome data.
AB  - BACKGROUND: GATK Best Practices workflows are widely used in large-scale
      sequencing projects and recommend post-alignment processing before variant
      calling. Two key post-processing steps include the computationally intensive
      local realignment around known INDELs and base quality score recalibration
      (BQSR). Both have been shown to reduce erroneous calls; however, the findings are
      mainly supported by the analytical pipeline that incorporates BWA and GATK
      UnifiedGenotyper. It is not known whether there is any benefit of post-processing
      and to what extent the benefit might be for pipelines implementing other methods,
      especially given that both mappers and callers are typically updated. Moreover,
      because sequencing platforms are upgraded regularly and the new platforms provide
      better estimations of read quality scores, the need for post-processing is also
      unknown. Finally, some regions in the human genome show high sequence divergence
      from the reference genome; it is unclear whether there is benefit from post
      processing in these regions. RESULTS: We used both simulated and NA12878 exome
      data to comprehensively assess the impact of post-processing for five or six
      popular mappers together with five callers. Focusing on chromosome 6p21.3, which
      is a region of high sequence divergence harboring the human leukocyte antigen
      (HLA) system, we found that local realignment had little or no impact on SNP
      calling, but increased sensitivity was observed in INDEL calling for the Stampy +
      GATK UnifiedGenotyper pipeline. No or only a modest effect of local realignment
      was detected on the three haplotype-based callers and no evidence of effect on
      Novoalign. BQSR had virtually negligible effect on INDEL calling and generally
      reduced sensitivity for SNP calling that depended on caller, coverage and level
      of divergence. Specifically, for SAMtools and FreeBayes calling in the regions
      with low divergence, BQSR reduced the SNP calling sensitivity but improved the
      precision when the coverage is insufficient. However, in regions of high
      divergence (e.g., the HLA region), BQSR reduced the sensitivity of both callers
      with little gain in precision rate. For the other three callers, BQSR reduced the
      sensitivity without increasing the precision rate regardless of coverage and
      divergence level. CONCLUSIONS: We demonstrated that the gain from post-processing
      is not universal; rather, it depends on mapper and caller combination, and the
      benefit is influenced further by sequencing depth and divergence level. Our
      analysis highlights the importance of considering these key factors in deciding
      to apply the computationally intensive post-processing to Illumina exome data.

PMID- 27716038
TI  - ChiLin: a comprehensive ChIP-seq and DNase-seq quality control and analysis
      pipeline.
AB  - BACKGROUND: Transcription factor binding, histone modification, and chromatin
      accessibility studies are important approaches to understanding the biology of
      gene regulation. ChIP-seq and DNase-seq have become the standard techniques for
      studying protein-DNA interactions and chromatin accessibility respectively, and
      comprehensive quality control (QC) and analysis tools are critical to extracting
      the most value from these assay types. Although many analysis and QC tools have
      been reported, few combine ChIP-seq and DNase-seq data analysis and quality
      control in a unified framework with a comprehensive and unbiased reference of
      data quality metrics. RESULTS: ChiLin is a computational pipeline that automates
      the quality control and data analyses of ChIP-seq and DNase-seq data. It is
      developed using a flexible and modular software framework that can be easily
      extended and modified. ChiLin is ideal for batch processing of many datasets and
      is well suited for large collaborative projects involving ChIP-seq and DNase-seq
      from different designs. ChiLin generates comprehensive quality control reports
      that include comparisons with historical data derived from over 23,677 public
      ChIP-seq and DNase-seq samples (11,265 datasets) from eight literature-based
      classified categories. To the best of our knowledge, this atlas represents the
      most comprehensive ChIP-seq and DNase-seq related quality metric resource
      currently available. These historical metrics provide useful heuristic quality
      references for experiment across all commonly used assay types. Using
      representative datasets, we demonstrate the versatility of the pipeline by
      applying it to different assay types of ChIP-seq data. The pipeline software is
      available open source at https://github.com/cfce/chilin . CONCLUSION: ChiLin is a
      scalable and powerful tool to process large batches of ChIP-seq and DNase-seq
      datasets. The analysis output and quality metrics have been structured into user
      friendly directories and reports. We have successfully compiled 23,677 profiles
      into a comprehensive quality atlas with fine classification for users.

PMID- 27716039
TI  - Parametric bootstrapping for biological sequence motifs.
AB  - BACKGROUND: Biological sequence motifs drive the specific interactions of
      proteins and nucleic acids. Accordingly, the effective computational discovery
      and analysis of such motifs is a central theme in bioinformatics. Many practical
      questions about the properties of motifs can be recast as random sampling
      problems. In this light, the task is to determine for a given motif whether a
      certain feature of interest is statistically unusual among relevantly similar
      alternatives. Despite the generality of this framework, its use has been
      frustrated by the difficulties of defining an appropriate reference class of
      motifs for comparison and of sampling from it effectively. RESULTS: We define two
      distributions over the space of all motifs of given dimension. The first is the
      maximum entropy distribution subject to mean information content, and the second
      is the truncated uniform distribution over all motifs having information content
      within a given interval. We derive exact sampling algorithms for each. As a proof
      of concept, we employ these sampling methods to analyze a broad collection of
      prokaryotic and eukaryotic transcription factor binding site motifs. In addition
      to positional information content, we consider the informational Gini coefficient
      of the motif, a measure of the degree to which information is evenly distributed
      throughout a motif's positions. We find that both prokaryotic and eukaryotic
      motifs tend to exhibit higher informational Gini coefficients (IGC) than would be
      expected by chance under either reference distribution. As a second application,
      we apply maximum entropy sampling to the motif p-value problem and use it to give
      elementary derivations of two new estimators. CONCLUSIONS: Despite the historical
      centrality of biological sequence motif analysis, this study constitutes to our
      knowledge the first use of principled null hypotheses for sequence motifs given
      information content. Through their use, we are able to characterize for the first
      time differerences in global motif statistics between biological motifs and their
      null distributions. In particular, we observe that biological sequence motifs
      show an unusual distribution of IGC, presumably due to biochemical constraints on
      the mechanisms of direct read-out.

PMID- 27716040
TI  - A decision analysis model for KEGG pathway analysis.
AB  - BACKGROUND: The knowledge base-driven pathway analysis is becoming the first
      choice for many investigators, in that it not only can reduce the complexity of
      functional analysis by grouping thousands of genes into just several hundred
      pathways, but also can increase the explanatory power for the experiment by
      identifying active pathways in different conditions. However, current approaches
      are designed to analyze a biological system assuming that each pathway is
      independent of the other pathways. RESULTS: A decision analysis model is
      developed in this article that accounts for dependence among pathways in time
      course experiments and multiple treatments experiments. This model introduces a
      decision coefficient-a designed index, to identify the most relevant pathways in
      a given experiment by taking into account not only the direct determination
      factor of each Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway itself, but
      also the indirect determination factors from its related pathways. Meanwhile, the
      direct and indirect determination factors of each pathway are employed to
      demonstrate the regulation mechanisms among KEGG pathways, and the sign of
      decision coefficient can be used to preliminarily estimate the impact direction
      of each KEGG pathway. The simulation study of decision analysis demonstrated the
      application of decision analysis model for KEGG pathway analysis. CONCLUSIONS: A
      microarray dataset from bovine mammary tissue over entire lactation cycle was
      used to further illustrate our strategy. The results showed that the decision
      analysis model can provide the promising and more biologically meaningful
      results. Therefore, the decision analysis model is an initial attempt of
      optimizing pathway analysis methodology.

PMID- 27716042
TI  - Erratum to: Transcriptome responses to temperature, water availability and
      photoperiod are conserved among mature trees of two divergent Douglas-fir
      provenances from a coastal and an interior habitat.

PMID- 27716041
TI  - Glycoside hydrolases family 20 (GH20) represent putative virulence factors that
      are shared by animal pathogenic oomycetes, but are absent in phytopathogens.
AB  - BACKGROUND: Although interest in animal pathogenic oomycetes is increasing, the
      molecular basis mediating oomycete-animal relationships remains virtually
      unknown. Crinkler (CRN) genes, which have been traditionally associated with the
      cytotoxic activity displayed by plant pathogenic oomycetes, were recently
      detected in transcriptome sequences from the entomopathogenic oomycete Lagenidium
      giganteum, suggesting that these genes may represent virulence factors conserved
      in both animal and plant pathogenic oomycetes. In order to further characterize
      the L. giganteum pathogenome, an on-going genomic survey was mined to reveal
      novel putative virulence factors, including canonical oomycete effectors Crinkler
      13 (CRN13) orthologs. These novel sequences provided a basis to initiate gene
      expression analyses and determine if the proposed L. giganteum virulence factors
      are differentially expressed in the presence of mosquito larvae (Aedes aegypti).
      RESULTS: Sequence analyses revealed that L. giganteum express CRN13 transcripts.
      The predicted proteins, like other L. giganteum CRNs, contained a conserved LYLA
      motif at the N terminal, but did not display signal peptides. In contrast, other
      potential virulence factors, such as Glycoside Hydrolases family 20
      (hexosaminidase) and 37 (trehalase) proteins (GH20 and GH37), contained
      identifiable signal peptides. Genome mining demonstrated that GH20 genes are
      absent from phytopathogenic oomycete genomes, and that the L. giganteum GH20
      sequence is the only reported peronosporalean GH20 gene. All other oomycete GH20
      homologs were retrieved from animal pathogenic, saprolegnialean genomes.
      Furthermore, phylogenetic analyses demonstrated that saprolegnialean and
      peronosporalean GH20 protein sequences clustered in unrelated clades. The
      saprolegnialean GH20 sequences appeared as a strongly supported, monophyletic
      group nested within an arthropod-specific clade, suggesting that this gene was
      acquired via a lateral gene transfer event from an insect or crustacean genome.
      In contrast, the L. giganteum GH20 protein sequence appeared as a sister taxon to
      a plant-specific clade that included exochitinases with demonstrated insecticidal
      activities. Finally, gene expression analyses demonstrated that the L. giganteum
      GH20 gene expression level is significantly modulated in the presence of mosquito
      larvae. In agreement with the protein secretion predictions, CRN transcripts did
      not show any differential expression. CONCLUSIONS: These results identified GH20
      enzymes, and not CRNs, as potential pathogenicity factors shared by all animal
      pathogenic oomycetes.

PMID- 27716043
TI  - The succession pattern of soil microbial communities and its relationship with
      tobacco bacterial wilt.
AB  - BACKGROUND: The interaction mechanism between crop and soil microbial communities
      is a key issue in both agriculture and soil ecology. However, how soil microbial
      communities respond to crop planting and ultimately affect crop health still
      remain unclear. In this research, we explored how soil microbial communities
      shifted during tobacco cultivation under different rotation systems (control,
      maize rotation, lily rotation and turnip rotation). RESULTS: Our analyses showed
      that soil microbial communities had a general response pattern to tobacco
      planting, as the abundances of Proteobacteria and Planctomycetes increased while
      Acidobacteria and Verrucomicrobia decreased during tobacco cultivation, no matter
      which rotation system was adopted. Notably, tobacco decreased the diversity and
      co-occurrence of soil microorganisms, but maize rotation might suppress tobacco
      bacterial wilt by alleviating the decrease in biodiversity and co-occurrence.
      Molecular ecological network analysis indicated that there was stronger
      competition between potential disease suppressive (e.g., Acidobacteria) and
      inducible bacteria (e.g., Chloroflexi) in maize rotation systems. Both soil
      properties (e.g., pH, Ca content) and microbial communities of tobacco mature
      period depended on their counterparts of fallow period, and all these factors
      shaped tobacco disease comprehensively. CONCLUSIONS: Both soil microbial
      communities of fallow stage and tobacco selection shaped the communities of
      tobacco mature stage. And effective rotation crop (maize) could decrease the
      incidence of tobacco bacterial wilt by alleviating the decrease in diversity and
      co-occurrences of microbial populations. This study would deepen our
      understanding about succession mechanism of soil microbial communities during
      crop cultivation and their relationship with crop health.

PMID- 27716044
TI  - Identification and expression analysis of OsLPR family revealed the potential
      roles of OsLPR3 and 5 in maintaining phosphate homeostasis in rice.
AB  - BACKGROUND: Phosphorus (P), an essential macronutrient, is often limiting in
      soils and affects plant growth and development. In Arabidopsis thaliana, Low
      Phosphate Root1 (LPR1) and its close paralog LPR2 encode multicopper oxidases
      (MCOs). They regulate meristem responses of root system to phosphate (Pi)
      deficiency. However, the roles of LPR gene family in rice (Oryza sativa) in
      maintaining Pi homeostasis have not been elucidated as yet. RESULTS: Here, the
      identification and expression analysis for the homologs of LPR1/2 in rice were
      carried out. Five homologs, hereafter referred to as OsLPR1-5, were identified in
      rice, which are distributed on chromosome1 over a range of 65 kb. Phylogenetic
      analysis grouped OsLPR1/3/4/5 and OsLPR2 into two distinct sub-clades with OsLPR3
      and 5 showing close proximity. Quantitative real-time RT-PCR (qRT-PCR) analysis
      revealed higher expression levels of OsLPR3-5 and OsLPR2 in root and shoot,
      respectively. Deficiencies of different nutrients ie, P, nitrogen (N), potassium
      (K), magnesium (Mg) and iron (Fe) exerted differential and partially overlapping
      effects on the relative expression levels of the members of OsLPR family. Pi
      deficiency (-P) triggered significant increases in the relative expression levels
      of OsLPR3 and 5. Strong induction in the relative expression levels of OsLPR3 and
      5 in osphr2 suggested their negative transcriptional regulation by OsPHR2.
      Further, the expression levels of OsLPR3 and 5 were either attenuated in ossiz1
      and ospho2 or augmented in rice overexpressing OsSPX1. CONCLUSIONS: The results
      from this study provided insights into the evolutionary expansion and a likely
      functional divergence of OsLPR family with potential roles of OsLPR3 and 5 in the
      maintenance of Pi homeostasis in rice.

PMID- 27716045
TI  - Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel
      FIT-regulated genes, iron deficiency marker genes and functional gene networks.
AB  - BACKGROUND: FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the
      central regulator of iron uptake in Arabidopsis thaliana roots. We performed
      transcriptome analyses of six day-old seedlings and roots of six week-old plants
      using wild type, a fit knock-out mutant and a FIT over-expression line grown
      under iron-sufficient or iron-deficient conditions. We compared genes regulated
      in a FIT-dependent manner depending on the developmental stage of the plants. We
      assembled a high likelihood dataset which we used to perform co-expression and
      functional analysis of the most stably iron deficiency-induced genes. RESULTS:
      448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT
      regulated in root and seedling samples and included 13 novel FIT-dependent genes.
      Three hundred thirty-one genes showed differential regulation in response to the
      presence and absence of FIT only in the root samples, while this was the case for
      83 genes in the seedling samples. We assembled a virtual dataset of iron
      regulated genes based on a total of 14 transcriptomic analyses of iron-deficient
      and iron-sufficient wild-type plants to pinpoint the best marker genes for iron
      deficiency and analyzed this dataset in depth. Co-expression analysis of this
      dataset revealed 13 distinct regulons part of which predominantly contained
      functionally related genes. CONCLUSIONS: We could enlarge the list of FIT
      dependent genes and discriminate between genes that are robustly FIT-regulated in
      roots and seedlings or only in one of those. FIT-regulated genes were mostly
      induced, few of them were repressed by FIT. With the analysis of a virtual
      dataset we could filter out and pinpoint new candidates among the most reliable
      marker genes for iron deficiency. Moreover, co-expression and functional analysis
      of this virtual dataset revealed iron deficiency-induced and functionally
      distinct regulons.

PMID- 27716046
TI  - Immune analysis of expression of IL-17 relative ligands and their receptors in
      bladder cancer: comparison with polyp and cystitis.
AB  - BACKGROUND: Bladder cancer, cystitis and bladder polyp are the most common
      urinary system diseases all over the world. Our former research results show that
      IL-17A and IL-17 F contribute to the pathogenesis of benign prostatic hyperplasia
      (BPH) and prostate cancer (Pca) while IL-17E interacting with IL-17RB might have
      an anti-tumor effect. RESULTS: Using imunohistochemistry, we systemically
      compared immunoreactivity of ligands (IL-17A, E and F) and receptors (IL-17RA, IL
      17RB and IL-17RC) of IL-17 family, infiltration of inflammatory cells and changes
      of structural cells (fibroblast cells, smooth muscle and vascular endothelial
      cells) in sections of bladder tissues from subjects with bladder cancer, cystitis
      and bladder polyp. Compared with subjects with cystitis, immunoreactivity for IL
      17A, IL-17 F and IL-17RC was significantly elevated in the group of bladder
      cancer (p < 0.01), while immunoreactivity of IL-17E, IL-17RA and IL-17RB, and the
      infiltrating neutrophils were decreased (p < 0.05). The numbers of infiltrating
      lymphocytes and phagocytes and CD31+ blood vessels and immunoreactivity of CD90+
      fibroblasts were also elevated in patients with bladder cancer compared with
      those of cystitis. The patterns of IL-17 ligands and receptors, and inflammatory
      cells and structural cells varied in cystitis, bladder polyp and bladder cancer.
      In bladder cancer, immunoreactivity of IL-17E and IL-17 F was positively
      correlated with smooth muscles and lymphocytes, respectively. In addition,
      immunoreactivity of IL-17A and IL-17E was positively correlated with their
      receptors IL-17RA and IL-17RB respectively. CONCLUSIONS: The data suggest that
      changed patterns of expression of the IL-17 cytokine family ligands and receptors
      might be associated with infiltration of inflammatory cells and structural cells
      (CD90+ fibroblasts and CD31+ blood vessels), which might also contribute to
      occurrence and development in bladder cancer.

PMID- 27716047
TI  - Intranasal immunization with recombinant Toxoplasma gondii actin depolymerizing
      factor confers protective efficacy against toxoplasmosis in mice.
AB  - BACKGROUND: Toxoplasma gondii is an opportunistic protozoan closely associated
      with AIDS and vertical transmission. T. gondii actin depolymerizing factor
      (TgADF) plays an important role in actin cytoskeleton remodeling, and it is
      required to invade host cells. TgADF was a promising vaccine candidate. To
      observe the immunological changes and protective efficacy of recombinant TgADF
      protein (rTgADF) against T. gondii infection, we optimized the intranasal
      immunization dose of rTgADF and analyzed the survival rate and tachyzoite loads
      in mouse tissues after oral challenge with T. gondii tachyzoites. RESULTS: rTgADF
      was prepared, purified, and combined with mouse anti-His antibody and rabbit anti
      T. gondii serum. After intranasal immunization with 10 MUg, 20 MUg, 30 MUg, or 40
      MUg of rTgADF, the 30-MUg group elicited high levels of secretory IgA (sIgA) in
      nasal, intestinal, and vesical washes, raised IgG titres in the sera, strong
      proliferation of splenocytes, and increased secretion of IL-2 and IFN-gamma when
      compared with the control group. When the mice were orally challenged with T.
      gondii, an increase in the survival rate (36.36 %) and a decrease in the
      tachyzoite loads in the liver (67.77 %) and brain (51.01 %) were observed.
      CONCLUSIONS: Our findings demonstrate that intranasal immunization with rTgADF
      can simultaneously trigger mucosal and systemic immune responses and protect the
      mice against T. gondii infection.

PMID- 27716048
TI  - Glycan-binding F-box protein from Arabidopsis thaliana protects plants from
      Pseudomonas syringae infection.
AB  - BACKGROUND: A small group of F-box proteins consisting of a conserved F-box
      domain linked to a domain homologous to the glycan-binding protein has been
      identified within the genome of Arabidopsis thaliana. Previously, the so-called F
      box-Nictaba protein, encoded by the gene At2g02360, was shown to be a functional
      lectin which binds N-acetyllactosamine structures. Here, we present a detailed
      qRT-PCR expression analysis of F-box-Nictaba in Arabidopsis plants upon different
      stresses and hormone treatments. RESULTS: Expression of the F-box-Nictaba gene
      was enhanced after plant treatment with salicylic acid and after plant infection
      with the virulent Pseudomonas syringae pv. tomato strain DC3000 (Pst DC3000).
      beta-glucuronidase histochemical staining of transgenic Arabidopsis plants
      displayed preferential activity of the At2g02360 promoter in trichomes present on
      young rosette leaves. qRT-PCR analyses confirmed high expression of F-box-Nictaba
      in leaf trichomes. A. thaliana plants overexpressing the gene showed less disease
      symptoms after Pst DC3000 infection with reduced bacterial colonization compared
      to infected wild type and F-box-Nictaba knock-out plants. CONCLUSIONS: Our data
      show that the Arabidopsis F-box-Nictaba gene is a stress-inducible gene
      responsive to SA, bacterial infection and heat stress, and is involved in
      salicylic acid related plant defense responses. This knowledge enriched our
      understanding of the physiological importance of F-box-Nictaba, and can be used
      to create plants with better performance in changing environmental conditions.

PMID- 27716050
TI  - Erratum to: Genomic and expression analyses of Tursiops truncatus T cell receptor
      gamma (TRG) and alpha/delta (TRA/TRD) loci reveal a similar basic public
      gammadelta repertoire in dolphin and human.

PMID- 27716049
TI  - Crystal structure and DNA binding activity of a PadR family transcription
      regulator from hypervirulent Clostridium difficile R20291.
AB  - BACKGROUND: Clostridium difficile is a spore-forming obligate anaerobe that can
      remain viable for extended periods, even in the presence of antibiotics, which
      contributes to the persistence of this bacterium as a human pathogen during host
      to-host transmission and in hospital environments. We examined the structure and
      function of a gene product with the locus tag CDR20291_0991 (cdPadR1) as part of
      our broader goal aimed at elucidating transcription regulatory mechanisms
      involved in virulence and antibiotic resistance of the recently emergent
      hypervirulent C. difficile strain R20291. cdPadR1 is genomically positioned near
      genes that are involved in stress response and virulence. In addition, it was
      previously reported that cdPadR1 and a homologue from the historical C. difficile
      strain 630 (CD630_1154) were differentially expressed when exposed to stressors,
      including antibiotics. RESULTS: The crystal structure of cdPadR1 was determined
      to 1.9 A resolution, which revealed that it belongs to the PadR-s2 subfamily of
      PadR transcriptional regulators. cdPadR1 binds its own promoter and other
      promoter regions from within the C. difficile R20291 genome. DNA binding
      experiments demonstrated that cdPadR1 binds a region comprised of inverted
      repeats and an AT-rich core with the predicted specific binding motif,
      GTACTAT(N2)ATTATA(N)AGTA, within its own promoter that is also present in 200
      other regions in the C. difficile R20291 genome. Mutation of the highly conserved
      W in alpha4 of the effector binding/oligomerization domain, which is predicted to
      be involved in multi-drug recognition and dimerization in other PadR-s2 proteins,
      resulted in alterations of cdPadR1 binding to the predicted binding motif,
      potentially due to loss of higher order oligomerization. CONCLUSIONS: Our results
      indicate that cdPadR1 binds a region within its own promoter consisting of the
      binding motif GTACTAT(N2)ATTATA(N)AGTA and seems to associate non-specifically
      with longer DNA fragments in vitro, which may facilitate promoter and motif
      searching. This suggests that cdPadR1 acts as a transcriptional auto-regulator,
      binding specific sites within its own promoter, and is part of a broad gene
      regulatory network involved, in part, with environmental stress response,
      antibiotic resistance and virulence.

PMID- 27716051
TI  - Development of EMS-induced mutation population for amylose and resistant starch
      variation in bread wheat (Triticum aestivum) and identification of candidate
      genes responsible for amylose variation.
AB  - BACKGROUND: Starch is a major part of cereal grain. It comprises two glucose
      polymer fractions, amylose (AM) and amylopectin (AP), that make up about 25 and
      75 % of total starch, respectively. The ratio of the two affects processing
      quality and digestibility of starch-based food products. Digestibility determines
      nutritional quality, as high amylose starch is considered a resistant or healthy
      starch (RS type 2) and is highly preferred for preventive measures against
      obesity and related health conditions. The topic of nutrition security is
      currently receiving much attention and consumer demand for food products with
      improved nutritional qualities has increased. In bread wheat (Triticum aestivum
      L.), variation in amylose content is narrow, hence its limited improvement.
      Therefore, it is necessary to produce wheat lines or populations showing wide
      variation in amylose/resistant starch content. In this study, a set of EMS
      induced M4 mutant lines showing dynamic variation in amylose/resistant starch
      content were produced. Furthermore, two diverse mutant lines for amylose content
      were used to study quantitative expression patterns of 20 starch metabolic
      pathway genes and to identify candidate genes for amylose biosynthesis. RESULTS:
      A population comprising 101 EMS-induced mutation lines (M4 generation) was
      produced in a bread wheat (Triticum aestivum) variety. Two methods of amylose
      measurement in grain starch showed variation in amylose content ranging from ~3
      to 76 % in the population. The method of in vitro digestion showed variation in
      resistant starch content from 1 to 41 %. One-way ANOVA analysis showed
      significant variation (p < 0.05) in amylose and resistant starch content within
      the population. A multiple comparison test (Dunnett's test) showed that
      significant variation in amylose and resistant starch content, with respect to
      the parent, was observed in about 89 and 38 % of the mutant lines, respectively.
      Expression pattern analysis of 20 starch metabolic pathway genes in two diverse
      mutant lines (low and high amylose mutants) showed higher expression of key genes
      of amylose biosynthesis (GBSSI and their isoforms) in the high amylose mutant
      line, in comparison to the parent. Higher expression of amylopectin biosynthesis
      (SBE) was observed in the low amylose mutant lines. An additional six candidate
      genes showed over-expression (BMY, SPA) and reduced-expression (SSIII, SBEI,
      SBEIII, ISA3) in the high amylose mutant line, indicating that other starch
      metabolic genes may also contribute to amylose biosynthesis. CONCLUSION: In this
      study a set of 101 EMS-induced mutant lines (M4 generation) showing variation in
      amylose and resistant starch content in seed were produced. This population
      serves as useful germplasm or pre-breeding material for genome-wide study and
      improvement of starch-based processing and nutrition quality in wheat. It is also
      useful for the study of the genetic and molecular basis of amylose/resistant
      starch variation in wheat. Furthermore, gene expression analysis of 20 starch
      metabolic genes in the two diverse mutant lines (low and high amylose mutants)
      indicates that in addition to key genes, several other genes (such as
      phosphorylases, isoamylases, and pullulanases) may also be involved in
      contributing to amylose/amylopectin biosynthesis.

PMID- 27716052
TI  - De novo assembly and transcriptome characterization of spruce dwarf mistletoe
      Arceuthobium sichuanense uncovers gene expression profiling associated with plant
      development.
AB  - BACKGROUND: The parasitic flowering plant dwarf mistletoe (Arceuthobium spp.,
      Viscaceae) is one of the most destructive forest pests, posing a major threat to
      numerous conifer species worldwide. Arceuthobium sichuanense (spruce dwarf
      mistletoe, SDM) infects Qinghai spruce (Picea crassifolia) and causes severe
      damage to spruce forests in Northwest China. SDM is a Chinese native parasitic
      plant and acquires carbohydrates and mineral nutrition from its hosts. However,
      underlying molecular basis of the physiological development is largely unknown.
      Investigations of these physiological traits have been hampered by the lack of
      genomic resources for this species. RESULTS: In this study, to investigate the
      transcriptomic processes underlying physiological traits and development in SDM,
      we used RNA from four major tissues (i.e., shoots, flowers, fruits, and seeds)
      for de novo assembly and to annotate the transcriptome of this species. We
      uncovered the annotated transcriptome and performed whole genome expression
      profiling to uncover transcriptional dynamics during physiological development,
      and we identified key gene categories involved in the process of sexual
      development. The assembled SDM transcriptome reported in this work contains
      331,347 assembled transcripts; 226,687 unigenes were functionally annotated by
      Gene Ontology analysis. RNA-Seq analysis using this reference transcriptome
      identified 22,641 differentially expressed genes from shoots, flowers, fruits,
      and seeds. These genes are enriched in processes including organic substance
      metabolism, cellular metabolism, biosynthesis, and cellular component. In
      addition, genes related to transport, transcription, hormone biosynthesis and
      signaling, carbohydrate metabolism, and photosynthesis were differentially
      expressed between tissues. CONCLUSION: This work reveals tissue-specific gene
      expression patterns and pathways of SDM and implied to a difference between
      photosynthetic and non-photosynthetic tissues in plants. The data can potentially
      be used for future investigations on endophytic parasitism and SDM-spruce
      interaction, and it dramatically increases the available genomic resources for
      Arceuthobium and dwarf mistletoe communities. This preliminary study of the
      Arceuthobium transcriptome provides excellent opportunities for characterizing
      plant parasitic genes with unknown functions.

PMID- 27716053
TI  - Metatranscriptome analysis reveals bacterial symbiont contributions to lower
      termite physiology and potential immune functions.
AB  - BACKGROUND: Symbioses throughout the animal kingdom are known to extend
      physiological and ecological capabilities to hosts. Insect-microbe associations
      are extremely common and are often related to novel niche exploitation, fitness
      advantages, and even speciation events. These phenomena include expansions in
      host diet, detoxification of insecticides and toxins, and increased defense
      against pathogens. However, dissecting the contributions of individual groups of
      symbionts at the molecular level is often underexplored due to methodological and
      analytical limitations. Termites are one of the best studied systems for
      physiological collaborations between host and symbiota; however, most work in
      lower termites (those with bacterial and protist symbionts) focuses on the
      eukaryotic members of this symbiotic consortium. Here we present a
      metatranscriptomic analysis which provides novel insights into bacterial
      contributions to the holobiont of the eastern subterranean termite,
      Reticulitermes flavipes, in the presence and absence of a fungal pathogen.
      RESULTS: Using a customized ribodepletion strategy, a metatranscriptome assembly
      was obtained representing the host termite as well as bacterial and protist
      symbiota. Sequence data provide new insights into biosynthesis, catabolism, and
      transport of major organic molecules and ions by the gut consortium, and
      corroborate previous findings suggesting that bacteria play direct roles in
      nitrogen fixation, amino acid biosynthesis, and lignocellulose digestion. With
      regard to fungal pathogen challenge, a total of 563 differentially expressed
      candidate host and symbiont contigs were identified (162 up- and 401
      downregulated; alpha/FDR = 0.05) including an upregulated bacterial
      amidohydrolase. CONCLUSIONS: This study presents the most complete bacterial
      metatranscriptome from a lower termite and provides a framework on which to build
      a more complete model of termite-symbiont interactions including, but not limited
      to, digestion and pathogen defense.

PMID- 27716054
TI  - Ethylene responsive transcription factor ERF109 retards PCD and improves salt
      tolerance in plant.
AB  - BACKGROUND: The ultimate goal of this work was to detect the role of
      transcription factors (TFs) concordantly expressed with genes related to
      programmed cell death (PCD) during PCD and salt stress. This work was based on
      the hypothesis that TFs and their driven genes likely co-express under different
      stimuli. The conserved superfamily ethylene responsive factor (AP2/ERF) draw
      attention of the present study as it participates in the response to biotic and
      abiotic stimuli as well as to program cell death (PCD). RESULTS: RNA-Seq analysis
      was done for tobacco (N. benthamiana) leaves exposed to oxalic acid (OA) at 20 mM
      for 0, 2, 6, 12 and 24 h to induce PCD. Genes up-regulated after 2 h of OA
      treatment with known function during PCD were utilized as landmarks to select TFs
      with concordant expression. Knockdown mutants of these TFs were generated in
      tobacco via virus induced gene silencing (VIGS) in order to detect their roles
      during PCD. Based on the results of PCD assay, knockout (KO) T-DNA insertion
      mutants of Arabidopsis as well as over-expression lines of two selected TFs,
      namely ERF109 and TFIID5, analogs to those in tobacco, were tested under salt
      stress (0, 100, 150 and 200 mM NaCl). CONCLUSIONS: Results of knockdown mutant
      tobacco cells confirmed the influence of these two TFs during PCD. Knockout
      insertion mutants and over-expression lines indicated the role of ERF109 in
      conferring salt tolerance in Arabidopsis.

PMID- 27716055
TI  - TLR9 mediates S. aureus killing inside osteoblasts via induction of oxidative
      stress.
AB  - BACKGROUND: Staphylococcus aureus is the principle causative pathogen of
      osteomyelitis and implant-associated bone infections. It is able to invade and to
      proliferate inside osteoblasts thus avoiding antibiotic therapy and the host
      immune system. Therefore, development of alternative approaches to stimulate host
      innate immune responses could be beneficial in prophylaxis against S. aureus
      infection. TLR9 is the intracellular receptor which recognizes unmethylated
      bacterial CpG-DNA and activates immune cells. Synthetic CpG-motifs containing
      oligodeoxynucleotide (CpG-ODNs) mimics the stimulatory effect of bacterial DNA.
      RESULTS: Osteoblast-like SAOS-2 cells were pretreated with CpG-ODN type-A 2216,
      type-B 2006, or negative CpG-ODN 2243 (negative control) 4 h before infection
      with S. aureus isolate EDCC 5055 (=DSM 28763). Intracellular bacteria were
      streaked on BHI plates 4 h and 20 h after infection. ODN2216 as well as ODN2006
      but not ODN2243 were able to significantly inhibit the intracellular bacterial
      growth because about 31 % as well as 43 % of intracellular S. aureus could
      survive the pretreatment of SAOS-2 cells with ODN2216 or ODN2006 respectively 4 h
      and 20 h post-infection. RT-PCR analysis of cDNAs from SAOS-2 cells showed that
      pretreatment with ODN2216 or ODN2006 stimulated the expression of TLR9.
      Pretreatment of SAOS-2 cells with ODN2216 or ODN2006 but not ODN2243 managed to
      induce reactive oxygen species (ROS) production inside osteoblasts as measured by
      flow cytometry analysis. Moreover, treating SAOS-2 cells with the antioxidant
      Diphenyleneiodonium (DPI) obviously reduced S. aureus killing ability of TLR9
      agonists mediated by oxidative stress. CONCLUSIONS: In this work we demonstrated
      for the first time that CPG-ODNs have inhibitory effects on S. aureus survival
      inside SAOS-2 osteoblast-like cell line. This effect was attributed to
      stimulation of TLR9 and subsequent induction of oxidative stress. Pretreatment of
      infected SAOS-2 cells with ROS inhibitors resulted in the abolishment of the CPG
      ODNs killing effects.

PMID- 27716056
TI  - Histone modifications facilitate the coexpression of bidirectional promoters in
      rice.
AB  - BACKGROUND: Bidirectional gene pairs are highly abundant and mostly co-regulated
      in eukaryotic genomes. The structural features of bidirectional promoters (BDPs)
      have been well studied in yeast, humans and plants. However, the underlying
      mechanisms responsible for the coexpression of BDPs remain understudied,
      especially in plants. RESULTS: Here, we characterized chromatin features
      associated with rice BDPs. Several unique chromatin features were present in rice
      BDPs but were missing from unidirectional promoters (UDPs), including
      overrepresented active histone marks, canonical nucleosomes and underrepresented
      H3K27me3. In particular, overrepresented active marks (H3K4ac, H4K12ac, H4K16ac,
      H3K4me2 and H3K36me3) were truly overrepresented in type I BDPs but not in the
      other two BDPs, based on a Kolmogorov-Smirnov test. CONCLUSIONS: Our analyses
      indicate that active marks (H3K4ac, H4K12ac, H4K16ac, H3K4me3, H3K9ac and
      H3K27ac) may coordinate with repressive marks (H3K27me3 and H3K9me1/3) to build a
      unique chromatin structure that favors the coregulation of bidirectional gene
      pairs. Thus, our findings help to enhance the understanding of unique epigenetic
      mechanisms that regulate bidirectional gene pairs and may improve the
      manipulation of gene pairs for crop bioengineering.

PMID- 27716058
TI  - Ascertainment bias from imputation methods evaluation in wheat.
AB  - BACKGROUND: Whole-genome genotyping techniques like Genotyping-by-sequencing
      (GBS) are being used for genetic studies such as Genome-Wide Association (GWAS)
      and Genomewide Selection (GS), where different strategies for imputation have
      been developed. Nevertheless, imputation error may lead to poor performance (i.e.
      smaller power or higher false positive rate) when complete data is not required
      as it is for GWAS, and each marker is taken at a time. The aim of this study was
      to compare the performance of GWAS analysis for Quantitative Trait Loci (QTL) of
      major and minor effect using different imputation methods when no reference panel
      is available in a wheat GBS panel. RESULTS: In this study, we compared the power
      and false positive rate of dissecting quantitative traits for imputed and not
      imputed marker score matrices in: (1) a complete molecular marker barley panel
      array, and (2) a GBS wheat panel with missing data. We found that there is an
      ascertainment bias in imputation method comparisons. Simulating over a complete
      matrix and creating missing data at random proved that imputation methods have a
      poorer performance. Furthermore, we found that when QTL were simulated with
      imputed data, the imputation methods performed better than the not-imputed ones.
      On the other hand, when QTL were simulated with not-imputed data, the not-imputed
      method and one of the imputation methods performed better for dissecting
      quantitative traits. Moreover, larger differences between imputation methods were
      detected for QTL of major effect than QTL of minor effect. We also compared the
      different marker score matrices for GWAS analysis in a real wheat phenotype
      dataset, and we found minimal differences indicating that imputation did not
      improve the GWAS performance when a reference panel was not available.
      CONCLUSIONS: Poorer performance was found in GWAS analysis when an imputed marker
      score matrix was used, no reference panel is available, in a wheat GBS panel.

PMID- 27716057
TI  - Acquisition and loss of virulence-associated factors during genome evolution and
      speciation in three clades of Bordetella species.
AB  - BACKGROUND: The genus Bordetella consists of nine species that include important
      respiratory pathogens such as the 'classical' species B. bronchiseptica, B.
      pertussis and B. parapertussis and six more distantly related and less
      extensively studied species. Here we analyze sequence diversity and gene content
      of 128 genome sequences from all nine species with focus on the evolution of
      virulence-associated factors. RESULTS: Both genome-wide sequence-based and gene
      content-based phylogenetic trees divide the genus into three species clades. The
      phylogenies are congruent between species suggesting genus-wide co-evolution of
      sequence diversity and gene content, but less correlated within species, mainly
      because of strain-specific presence of many different prophages. We compared the
      genomes with focus on virulence-associated genes and identified multiple clade
      specific, species-specific and strain-specific events of gene acquisition and
      gene loss, including genes encoding O-antigens, protein secretion systems and
      bacterial toxins. Gene loss was more frequent than gene gain throughout the
      evolution, and loss of hundreds of genes was associated with the origin of
      several species, including the recently evolved human-restricted B. pertussis and
      B. holmesii, B. parapertussis and the avian pathogen B. avium. CONCLUSIONS:
      Acquisition and loss of multiple genes drive the evolution and speciation in the
      genus Bordetella, including large scale gene loss associated with the origin of
      several species. Recent loss and functional inactivation of genes, including
      those encoding pertussis vaccine components and bacterial toxins, in individual
      strains emphasize ongoing evolution.

PMID- 27716059
TI  - IL-23 plasma level is strongly associated with CMV status and reactivation of CMV
      in renal transplant recipients.
AB  - BACKGROUND: Cytomegalovirus seropositivity is an independent risk factor for
      atherosclerosis in patients with ESRD. Donor CMV seropositivity is associated
      with higher graft loss. Dendritic cells, macrophages and Th17 lymphocytes are
      defined as producers of IL-23. IL-23 is thought to be involved in the promotion
      of Th17 cell polarization. Latent CMV-induced Th17 might be involved in the
      pathogenesis of CMV infection in patients with ESRD. We aimed to evaluate
      associations of Th17-dependent cytokines with ESRD, CMV status and post
      transplant outcome in kidney transplantation. RESULTS: IL-21 plasma levels were
      similar in patients and healthy controls (p = 0.47), whereas IL-9 (p = 0.02) and
      IL-23 (p < 0.0001) levels were significantly higher in ESRD patients. CMV
      seronegative (p = 0.002) and -seropositive (p < 0.001) patients had significantly
      higher IL-23 plasma levels than controls. CMV-seropositive patients showed
      excessively higher IL-23 (p < 0.001) plasma levels than CMV-seronegative
      patients. Patients with post-transplant CMV reactivation had higher IL-23 plasma
      levels than patients without CMV reactivation (p = 0.025). CONCLUSIONS: Our
      results indicate that latent CMV induces IL-23. IL-23 might be an inflammatory
      mediator of latent CMV infection in patients with ESRD and predisposes patients
      for post-transplant CMV reactivation.

PMID- 27716060
TI  - miR-27b shapes the presynaptic transcriptome and influences neurotransmission by
      silencing the polycomb group protein Bmi1.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNAs that are emerging as
      important post-transcriptional regulators of neuronal and synaptic development.
      The precise impact of miRNAs on presynaptic function and neurotransmission
      remains, however, poorly understood. RESULTS: Here, we identify miR-27b-an
      abundant neuronal miRNA implicated in neurological disorders-as a global
      regulator of the presynaptic transcriptome. miR-27b influences the expression of
      three quarters of genes associated with presynaptic function in cortical neurons.
      Contrary to expectation, a large majority of these genes are up-regulated by miR
      27b. This stimulatory effect is mediated by miR-27b-directed silencing of several
      transcriptional repressors that cooperate to suppress the presynaptic
      transcriptome. The strongest repressive activity appears to be mediated by Bmi1,
      a component of the polycomb repressive complex implicated in self-renewal of
      neural stem cells. miR-27b knockdown leads to reduced synaptogenesis and to a
      marked decrease in neural network activity, which is fully restored by RNAi
      mediated silencing of Bmi1. CONCLUSIONS: We conclude that silencing of Bmi1 by
      miR-27b relieves repression of the presynaptic transcriptome and supports
      neurotransmission in cortical networks. These results expand the repressive
      activity of Bmi1 to genes involved in synaptic function and identify a unique
      post-transcriptional circuitry that stimulates expression of synaptic genes and
      promotes synapse differentiation.

PMID- 27716061
TI  - Identification of manganese efficiency candidate genes in winter barley (Hordeum
      vulgare) using genome wide association mapping.
AB  - BACKGROUND: Manganese (Mn) has several essential functions in plants, including a
      role as cofactor in the oxygen evolving complex (OEC) of photosystem II (PSII).
      Manganese deficiency is a major plant nutritional disorder in winter cereals
      resulting in significant yield reductions and winter kill in more severe cases.
      Among the winter cereals, genotypes of winter barley are known to differ
      considerably in tolerance to Mn deficiency, but the genes controlling the Mn
      deficiency trait remains elusive. RESULTS: Experiments were conducted using 248
      barley varieties, cultivated in six distinct environments prone to induce Mn
      deficiency. High-throughput phenotyping for Mn deficiency was performed by
      chlorophyll a (Chl a) fluorescence analysis to quantify the quantum yield
      efficiency of PSII. High-throughput phenotyping in combination with ICP-OES based
      multi-element analyses allowed detection of marker-trait associations by genome
      wide association (GWA) mapping. Several key candidate genes were identified,
      including PSII subunit proteins, germin like proteins and Mn superoxide
      dismutase. The putative roles of the encoded proteins in Mn dependent metabolic
      processes are discussed. CONCLUSIONS: Fifty-four candidate genes were identified
      by Chl a fluorescence phenotyping and association genetics. Tolerance of plants
      to Mn deficiency, which is referred to as Mn efficiency, appeared to be a complex
      trait involving many genes. Moreover, the trait appeared to be highly dependent
      on the environmental conditions in field. This study provides the basis for an
      improved understanding of the parameters influencing Mn efficiency and is
      valuable in future plant breeding aiming at producing new varieties with improved
      tolerance to cultivation in soil prone to induce Mn deficiency.

PMID- 27716062
TI  - Genotyping of whole genome amplified reduced representation libraries reveals a
      cryptic population of Culicoides brevitarsis in the Northern Territory,
      Australia.
AB  - BACKGROUND: The advent of genotyping by Next Generation Sequencing has enabled
      rapid discovery of thousands of single nucleotide polymorphism (SNP) markers and
      high throughput genotyping of large populations at an affordable cost. Genotyping
      by sequencing (GBS), a reduced representation library sequencing method, allows
      highly multiplexed sequencing of genomic subsets. This method has limitations for
      small organisms with low amounts of genomic DNA, such as the bluetongue virus
      (BTV) vectors, Culicoides midges. RESULTS: This study employed the GBS method to
      isolate SNP markers de novo from whole genome amplified Culicoides brevitarsis
      genomic DNA. The individuals were collected from regions representing two
      different Australian patterns of BTV strain distribution: the Northern Territory
      (NT) and the east coast. We isolated 8145 SNPs using GBS. Phylogenetic analysis
      conducted using the filtered 3263 SNPs revealed the presence of a distinct C.
      brevitarsis sub-population in the NT and this was confirmed by analysis of
      mitochondrial DNA. Two loci showed a very strong signal for selection and were
      unique to the NT population. Bayesian analysis with STRUCTURE indicated a
      possible two-population cluster. CONCLUSIONS: The results suggest that genotyping
      vectors with high density markers in combination with biological and
      environmental data is useful. However, more extensive sampling over a wider
      spatial and temporal range is needed. The presence of sub-structure in
      populations and loci under natural selection indicates the need for further
      investigation of the role of vectors in shaping the two Australian systems of BTV
      transmission. The described workflow is transferable to genotyping of small, non
      model organisms, including arthropod vectors of pathogens of economic and medical
      importance.

PMID- 27716063
TI  - Measurement of adherence in a randomised controlled trial of a complex
      intervention: supported self-management for adults with learning disability and
      type 2 diabetes.
AB  - BACKGROUND: Reporting adherence to intervention delivery and uptake is a detailed
      way of describing what was actually delivered and received, in comparison to what
      was intended. Measuring and reporting adherence is not routinely done well in
      complex interventions. The OK Diabetes trial (ISRCTN41897033) aimed to develop
      and subsequently test the feasibility of implementing a supported self-management
      intervention in adults with a learning disability and type 2 diabetes. A key
      study objective was to develop a measure of adherence to the intervention.
      METHODS: We conducted a systematic review of published literature, extracting
      data from included papers using a standardised proforma. We undertook a narrative
      synthesis of papers to determine the form and content of methods for adherence
      measurement for self-management interventions in this population that had already
      been developed. We used the framework and data extraction form developed for the
      review as the basis for an adherence measurement tool that we applied in the OK
      Diabetes trial. RESULTS: The literature review found variability in the quality
      and content of adherence measurement and reporting, with no standardised
      approach. We were able to develop an adherence measure based upon the review, and
      populate it with data collected during the OK Diabetes trial. The adherence tool
      proved satisfactory for recording and measuring adherence in the trial.
      CONCLUSION: There remains a need for a standardised approach to adherence
      measurement in the field of complex interventions. We have shown that it is
      possible to produce a simple, feasible measure for assessing adherence in the OK
      Diabetes trial.

PMID- 27716064
TI  - Changes in selected metabolic parameters in patients over 65 receiving
      hydrochlorothiazide plus amiloride, atenolol or placebo in the MRC elderly trial.
AB  - BACKGROUND: Treatment of hypertension reduces incidence of stroke, myocardial
      infarction and heart failure perhaps partly by controlling different metabolic
      parameters. There is limited information regarding the changes in potassium,
      sodium, weight, cholesterol and glucose levels in patients using anti
      hypertensives. This study aimed to determine changes in potassium, sodium,
      glucose, cholesterol, weight, urea and urate levels in patients using anti
      hypertensives. Furthermore, to describe these changes and differences between the
      atenolol, hydrochlorothiazide plus amiloride and placebo arms of the Medical
      Research Council (MRC) elderly randomised controlled trial. METHODS: Patients
      were randomly allocated to one of the three treatment arms. Measurements were
      taken at baseline, end of year one and end of year two in 4396 subjects. Linear
      Mixed Models (LMM) were used to determine the longitudinal profiles of sodium,
      potassium, weight, cholesterol, glucose, urea and urate. Estimates of changes
      within groups and difference between groups were obtained. RESULTS: Patients
      randomised to receive hydrochlorothiazide + amiloride experienced a significantly
      greater mean reduction in potassium, sodium and weight compared to placebo at end
      of year one - mean differences in change -0.18 mmol/L, (95 % CI: -0.21, -0.15); 
      1.45 mmol/L, (95 % CI: -1.62, -1.29) and -0.46 kgs (95 % CI: -0.73, -0.20)
      respectively, and greater increases in cholesterol, urea and urate - mean
      differences in change 0.16 mmol/L, (95 % CI: 0.10,0.22); 0.77 mmol/L, (95 % CI:
      0.68, 0.87) and 53.10 MUmol/L, (95 % CI: 49.35, 56.85) respectively. Changes were
      in the same direction but smaller in the atenololarm except for potassium and
      weight (increases). No group differences in glucose were found. CONCLUSION:
      Results were in line with expectation except for lack of change in glucose in the
      hydrochlorothiazide + amiloride arms.

PMID- 27716065
TI  - CYP79D enzymes contribute to jasmonic acid-induced formation of aldoximes and
      other nitrogenous volatiles in two Erythroxylum species.
AB  - BACKGROUND: Amino acid-derived aldoximes and nitriles play important roles in
      plant defence. They are well-known as precursors for constitutive defence
      compounds such as cyanogenic glucosides and glucosinolates, but are also released
      as volatiles after insect feeding. Cytochrome P450 monooxygenases (CYP) of the
      CYP79 family catalyze the formation of aldoximes from the corresponding amino
      acids. However, the majority of CYP79s characterized so far are involved in
      cyanogenic glucoside or glucosinolate biosynthesis and only a few have been
      reported to be responsible for nitrogenous volatile production. RESULTS: In this
      study we analysed and compared the jasmonic acid-induced volatile blends of two
      Erythroxylum species, the cultivated South American crop species E. coca and the
      African wild species E. fischeri. Both species produced different nitrogenous
      compounds including aliphatic aldoximes and an aromatic nitrile. Four isolated
      CYP79 genes (two from each species) were heterologously expressed in yeast and
      biochemically characterized. CYP79D62 from E. coca and CYP79D61 and CYP79D60 from
      E. fischeri showed broad substrate specificity in vitro and converted L
      phenylalanine, L-isoleucine, L-leucine, L-tryptophan, and L-tyrosine into the
      respective aldoximes. In contrast, recombinant CYP79D63 from E. coca exclusively
      accepted L-tryptophan as substrate. Quantitative real-time PCR revealed that
      CYP79D60, CYP79D61, and CYP79D62 were significantly upregulated in jasmonic acid
      treated Erythroxylum leaves. CONCLUSIONS: The kinetic parameters of the enzymes
      expressed in vitro coupled with the expression patterns of the corresponding
      genes and the accumulation and emission of (E/Z)-phenylacetaldoxime, (E/Z)-indole
      3-acetaldoxime, (E/Z)-3-methylbutyraldoxime, and (E/Z)-2-methylbutyraldoxime in
      jasmonic acid-treated leaves suggest that CYP79D60, CYP79D61, and CYP79D62 accept
      L-phenylalanine, L-leucine, L-isoleucine, and L-tryptophan as substrates in vivo
      and contribute to the production of volatile and semi-volatile nitrogenous
      defence compounds in E. coca and E. fischeri.

PMID- 27716066
TI  - Maize plants can enter a standby mode to cope with chilling stress.
AB  - BACKGROUND: European Flint maize inbred lines are used as a source of adaptation
      to cold in most breeding programs in Northern Europe. A deep understanding of
      their adaptation strategy could thus provide valuable clues for further
      improvement, which is required in the current context of climate change. We
      therefore compared six inbreds and two derived Flint x Dent hybrids for their
      response to one-week at low temperature (10  degrees C day/7 or 4  degrees C
      night) during steady-state vegetative growth. RESULTS: Leaf growth was arrested
      during chilling treatment but recovered fast upon return to warm temperature, so
      that no negative effect on shoot biomass was measured. Gene expression analyses
      of the emerging leaf in the hybrids suggest that plants maintained a 'ready-to
      grow' state during chilling since cell cycle genes were not differentially
      expressed in the division zone and genes coding for expansins were on the
      opposite up-regulated in the elongation zone. In photosynthetic tissues, a strong
      reduction in PSII efficiency was measured. Chilling repressed chlorophyll
      biosynthesis; we detected accumulation of the precursor geranylgeranyl
      chlorophyll a and down-regulation of GERANYLGERANYL REDUCTASE (GGR) in mature
      leaf tissues. Excess light energy was mostly dissipated through fluorescence and
      constitutive thermal dissipation processes, rather than by light-regulated
      thermal dissipation. Consistently, only weak clues of xanthophyll cycle
      activation were found. CO2 assimilation was reduced by chilling, as well as the
      expression levels of genes encoding phosphoenolpyruvate carboxylase (PEPC),
      pyruvate orthophosphate dikinase (PPDK), and the small subunit of Rubisco.
      Accumulation of sugars was correlated with a strong decrease of the specific leaf
      area (SLA). CONCLUSIONS: Altogether, our study reveals good tolerance of the
      photosynthetic machinery of Northern European maize to chilling and suggests that
      growth arrest might be their strategy for fast recovery after a mild stress.

PMID- 27716067
TI  - Improving measurement-invariance assessments: correcting entrenched testing
      deficiencies.
AB  - BACKGROUND: Factor analysis historically focused on measurement while path
      analysis employed observed variables as though they were error-free. When factor-
      and path-analysis merged as structural equation modeling, factor analytic notions
      dominated measurement discussions - including assessments of measurement
      invariance across groups. The factor analytic tradition fostered disregard of
      model testing and consequently entrenched this deficiency in measurement
      invariance assessments. DISCUSSION: Applying contemporary model testing
      requirements to the so-called configural model initiating invariance assessments
      will improve future assessments but a substantial backlog of deficient
      assessments remain to be overcome. This article summarizes the issues,
      demonstrates the problem using a recent example, illustrates a superior model
      assessment strategy, and documents disciplinary entrenchment of inadequate
      testing as exemplified by the journal Organizational Research Methods. Employing
      the few methodologically and theoretically best, rather than precariously
      multiple, indicators of latent variables increases the likelihood of achieving
      properly causally specified structural equation models capable of displaying
      measurement invariance. Just as evidence of invalidity trumps reliability,
      evidence of configural model misspecification trumps invariant estimates of
      misspecified coefficients.

PMID- 27716069
TI  - Should every region use the same gastric cancer scanning and treatment
      approaches? let's reconsider: a northeastern turkey example.
AB  - BACKGROUND: The rate for upper gastrointestinal (UGI) cancers, and especially the
      rate for gastric cancer, varies from country to country and from region to region
      within country. In Turkey, the incidence of gastric cancer varies widely among
      regions due to the diverse cultures and accompanying food habits of the
      population. This study aimed to determine the endoscopic frequency of esophageal
      and gastric cancers and the usefulness of alarm symptoms in diagnosing gastric
      cancer in subjects undergoing endoscopy in northeastern Turkey. METHODS: This
      retrospective study was based on hospital records, reviewing the records of
      patients who had underdone esophago-gastro-duodenal (EGD) video endoscopy at two
      general hospitals in Erzurum. From July 2010 to January 2013, 25,037 patients
      from Erzurum underwent EGD procedures under either intravenous sedation or local
      anesthesia. Classifications of UGI cancer, based on location of the tumor, were
      defined as esophageal, cardia, cardia and fundus or corpus or all of these,
      corpus, corpus and antrum, and antrum. Metastasis was studied in 659 patients
      diagnosed with cancer. RESULTS: Throughout the study, 1,007 biopsy samples were
      reported as malignant tumors (719 gastric, 276 esophageal, and 12 duodenal
      cancers). The study considered the gastric cancer population under age 46, which
      included 99 (13.8 %) patients. Among them, the distribution of UGI cancer by age
      was as follows: under age 26 years, 9 patients (0.9 %); age 26-35 years, 30
      patients (3 %); and age 36-45 years, 60 patients (6 %). Overall, 298 patients
      (298/1007, 29.6 %) presented with localized disease, and 361 patients (35.9 %)
      had distant metastases at the time of diagnosis. CONCLUSIONS: We determined that
      UGI cancer patients are observed more frequently in northeastern Turkey than in
      western Turkey, Europe, and the USA. We believe that alarm symptoms and
      endoscopic scanning programs require new, region-specific criteria to diagnose
      UGI cancers in this region. For the patient groups with these different
      characteristics, we believe that new scanning, follow-up, and treatment
      strategies are needed that take into consideration differences in the
      histopathology of the tumors, their localization, and the patients' ages. TRIAL
      REGISTRATION: There is registration number. This study is "retrospective study".
      This study is "retrospectively registered".

PMID- 27716068
TI  - Developing physical activity counselling in primary care through participatory
      action approach.
AB  - BACKGROUND: Many adults are insufficiently physically active for health.
      Counselling is the main method to promote physical activity (PA) in primary care
      but often implemented inadequately. The aim of this study was to increase health
      professionals' i) know-how about health-related PA and PA counselling, ii)
      implementation and quality of PA counselling, iii) familiarity with and use of
      Physical Activity Prescription (PAP), iv) internal and external collaboration and
      v) use of electronic patient record system in PA counselling. METHODS: Four
      Finnish health centres participated. Each nominated a working group for reaching
      the goals through a 6-month development work, which was supported with monthly
      tutorials by the research group. The outcome evaluation of the development work
      included 19 variables, which reflected the five goals and were assessed before
      (baseline) and after the development work (follow-up). Variable-specific
      differences in proportions (%) and their 95 % confidence intervals (CI) between
      the time points indicated change. The measures were questionnaires to the health
      professionals (N = 75 at baseline and N = 80 at follow-up) and patients (N = 441
      and N = 431), professionals' record sheets on patient visits (N = 1008 and N =
      1000), and telephone interviews to external partners (N = 48 and N = 28). The
      process was evaluated with the extent the working group members participated in
      the development work and with the implementation of development actions.
      Assessment was based on meeting minutes of tutorials and working group meetings.
      RESULTS: Health professionals' familiarity with PAP (questionnaire, change 39 %
      points; 95 % CI 26.5 to 52.5) and use of PAP (questionnaire, 32 %-points; 95 % CI
      18.9 to 45.1 and record sheet, 4 %-points; 95 % CI 2.7 to 5.3) increased. A
      greater proportion of professionals had agreed in their working unit on using PAP
      (questionnaire, 32 %-points; 95 % CI 20.3 to 43.7) and used PAP as a referral to
      other health professionals (record sheet, 1 %-point; 95 % CI 0.3 to 1.7). Also
      the know-how of PA and PA counselling showed improvement but not statistically
      significantly. The working group members participated unevenly in the development
      work and had difficulties in allocating time for the work. This was seen in
      limited number of actions implemented. CONCLUSIONS: The study was able to achieve
      some improvements in the familiarity with and use of PAP and to lesser extent in
      the know-how of health-related PA and PA counselling. To observe changes in other
      goals, which targeted more at organisational, inter-professional and multi
      sectorial level, may have required more long-term actions.

PMID- 27716070
TI  - A potential marker of bare metal stent restenosis: monocyte count - to- HDL
      cholesterol ratio.
AB  - BACKGROUND: Oxidation and inflammation play significant roles in the pathogenesis
      of coronary artery diseases. Monocyte count to high-density lipoprotein (HDL)
      cholesterol ratio (MHR) is a new marker and has revealed as an indicator of
      inflammation in the literature. The present study aimed to search the effect of
      MHR on in-stent restenosis (ISR) in patients with stable or unstable angina
      pectoris undergoing bare-metal stent (BMS) implantation. METHODS: A total of 468
      consecutive stable or unstable angina pectoris patients (mean age 60.3 +/- 10.1
      and 70 % men) who had undergone successful BMS implantation were included the
      study. Serum samples were obtained before the procedure. RESULTS: The mean period
      between two coronary angiography procedures was 14 +/- 7.9 months. The baseline
      MHR levels were significantly higher in patients that had ISR (odds ratio, 3.64;
      95 % confidence interval, 2.45- 4.84; P < 0.001). Stent diameter, the time
      between the two coronary angiographic studies, uric acid and MHR levels emerged
      as independent predictors of ISR. CONCLUSIONS: Our results indicate that elevated
      MHR is an independent and powerful predictor of ISR in patients with stable or
      unstable angina pectoris who underwent successful BMS implantation.

PMID- 27716071
TI  - Effectiveness of cyclosporine as a treatment for steroid-resistant Cronkhite
      Canada syndrome; two case reports.
AB  - BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare non-inherited disorder,
      characterized by gastrointestinal polyposis and ectodermal changes. The
      pathophysiology remains unclear. Treatment with corticosteroids is considered the
      mainstay treatment because of its high efficacy. However, some patients have
      steroid-resistant CCS. The therapeutic strategy for steroid-resistant CCS is not
      yet established. We report two cases with steroid-resistant CCS that were
      effectively treated with cyclosporine (CyA). We evaluated the therapeutic
      strategy for steroid-resistant CCS based on reviews of previous reports. CASE
      PRESENTATION: Our patients with CCS were first treated with prednisolone. No
      clinical response was noted, and treatment with CyA was initiated. After
      beginning CyA treatment, both clinical symptoms and polyposis markedly improved.
      Up to the present, 55 cases of CCS treated with corticosteroids and their
      response were reported. Out of the 57 patients, including our 2 cases, 9 (16 %)
      did not respond clinically to corticosteroids. In 7 of the 9 steroid-resistant
      cases, the prognosis after corticosteroids treatment was described. In 5 of the 7
      steroid-resistant cases, immunosuppressive treatments induced remission. In 4 of
      these 5 cases, moreover, the key drug of treatments was calcineurin inhibitor.
      CONCLUSIONS: Treatment with calcineurin inhibitor, such as CyA, could be a
      potential option for steroid-resistant CCS.

PMID- 27716072
TI  - Wnt signaling contributes to vascular calcification by induction of matrix
      metalloproteinases.
AB  - BACKGROUND: Vascular calcifications such as arteriosclerosis, which is
      characterized by a calcificiation of the tunica media, represent major
      comorbidities e.g. in patients with chronic kidney disease (CKD). An essential
      step during the development of arteriosclerosis is the
      transdifferentiation/calcification of vascular smooth muscle cells (VSMC)
      resembling osteogenesis. The matrix metalloproteinases (MMP)-2 and -9 were shown
      to promote these VSMC calcifications and their inhibition is of therapeutic value
      to prevent arteriosclerosis in preclinical studies. Aiming for an understanding
      of the underlying regulatory mechanisms of MMPs we here investigated, if the MMP
      mediated VSMC calcification involves altered signaling of the Wnt pathway, which
      is known to impact osteogenesis. METHODS: We used an experimental in vitro model
      of vascular calcification. Transdifferentiation/calcification of murine VSMC was
      induced by elevated calcium and phosphorus levels. Calcification was assessed by
      calcium and alkaline phosphatase measurements. Activation/activity of the
      gelatinases MMP-2 and MMP-9 was assessed by conversion of fluorescence-labelled
      substrates. Activation of the Wnt pathway was analysed by a reporter gene assay.
      RESULTS: Besides pro-calcifying culture conditions, also activation of Wnt
      signaling by a specific agonist (under normal culture conditions) stimulated VSMC
      calcification accompanied by enhanced expression and secretion of the gelatinases
      MMP-2 and -9. Vice versa, recombinant MMP-2 and -9 induced a time-delayed
      activation of Wnt signaling after 72 h in VSMC but showed no direct effects after
      24-48 h. These effects were blocked by pharmacological inhibition of MMPs or of
      Wnt signaling. CONCLUSIONS: Our study suggests that the pro-calcifying
      environment in CKD induces Wnt signaling in VSMC which in turn contributes to the
      induction of MMPs which then foster the development of arteriosclerosis. Thus,
      besides MMP inhibition, the inhibition of Wnt signaling in VSMC might represent a
      therapeutic target for the prevention of vascular calcifications.

PMID- 27716073
TI  - Male-specific association between MT-ND4 11719 A/G polymorphism and ulcerative
      colitis: a mitochondria-wide genetic association study.
AB  - BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disorder of still
      unknown pathogenesis. Increasing evidence indicates that alterations in
      mitochondrial respiration and thus adenosine triphosphate (ATP) production are
      involved. This may contribute to mucosal energy deficiency and subsequently
      intestinal barrier malfunction, which is accepted to be a major hallmark of UC.
      Genetic alterations of the mitochondrial genome are one cause of mitochondrial
      dysfunction. However, less is known about mitochondrial gene polymorphisms in UC.
      Therefore, we aimed at identifying genetic associations between mitochondrial
      polymorphisms and UC. METHODS: German UC cases (n = 1062) and German healthy
      controls (n = 3030) were genotyped using the Affymetrix Genome-Wide Human SNP
      Array 6.0. The primary association analysis was to test for associations between
      mitochondrial single nucleotide polymorphisms (SNPs) and UC using Fisher's exact
      test in the total sample and stratified by sex. In addition, we tested for
      associations between mitochondrial haplogroups and UC and for interactions
      between the most promising mitochondrial SNPs and nuclear SNPs. An independent
      set of German subjects with 1625 UC cases and 3575 controls was used for
      replication. RESULTS: We identified a genetic association between the MT-ND4
      11719 A/G polymorphism and UC in the subgroup of males (rs2853495; odds ratio,
      1.40; 95 % confidence interval, 1.13 to 1.73; p = 0.002). This association was
      replicated in the second independent cohort. In the association analysis based on
      mitochondrial haplogroups the lowest p values were reached for haplogroups HV and
      T (p = 0.029 and 0.035). Haplogroup HV is determined by the mitochondrial 11719
      A/G polymorphism. Accordingly, this association was only found in the subgroup of
      males (p = 0.009). CONCLUSIONS: For the first time, we observed an association
      between the MT-ND4 11719 A/G polymorphism and UC. The gene MT-ND4 encodes for a
      subunit of the mitochondrial electron transport chain complex I, which is pivotal
      for ATP production and might therefore contribute to mucosal energy deficiency.
      The male-specific association indicates differences between males and females
      concerning the impact of mitochondrial gene polymorphisms on the development of
      UC. Further investigations of the functional mechanism underlying this
      association and the relevance of the gender-specificity are highly warranted.

PMID- 27716074
TI  - Methods for network meta-analysis of continuous outcomes using individual patient
      data: a case study in acupuncture for chronic pain.
AB  - BACKGROUND: Network meta-analysis methods, which are an extension of the standard
      pair-wise synthesis framework, allow for the simultaneous comparison of multiple
      interventions and consideration of the entire body of evidence in a single
      statistical model. There are well-established advantages to using individual
      patient data to perform network meta-analysis and methods for network meta
      analysis of individual patient data have already been developed for dichotomous
      and time-to-event data. This paper describes appropriate methods for the network
      meta-analysis of individual patient data on continuous outcomes. METHODS: This
      paper introduces and describes network meta-analysis of individual patient data
      models for continuous outcomes using the analysis of covariance framework.
      Comparisons are made between this approach and change score and final score only
      approaches, which are frequently used and have been proposed in the
      methodological literature. A motivating example on the effectiveness of
      acupuncture for chronic pain is used to demonstrate the methods. Individual
      patient data on 28 randomised controlled trials were synthesised. Consistency of
      endpoints across the evidence base was obtained through standardisation and
      mapping exercises. RESULTS: Individual patient data availability avoided the use
      of non-baseline-adjusted models, allowing instead for analysis of covariance
      models to be applied and thus improving the precision of treatment effect
      estimates while adjusting for baseline imbalance. CONCLUSIONS: The network meta
      analysis of individual patient data using the analysis of covariance approach is
      advocated to be the most appropriate modelling approach for network meta-analysis
      of continuous outcomes, particularly in the presence of baseline imbalance.
      Further methods developments are required to address the challenge of analysing
      aggregate level data in the presence of baseline imbalance.

PMID- 27716075
TI  - Culprit-only versus staged complete revascularization for patients with ST
      segment elevation myocardial infarction and Multivessel disease: a retrospective
      cohort study.
AB  - BACKGROUND: Multivessel disease (MVD) is common in patients with ST-segment
      elevation myocardial infarction (STEMI), but optimal treatment management remains
      undetermined. METHODS: In this retrospective cohort study, 602 consecutive STEMI
      patients with MVD were enrolled between January 1, 2010 and October 1, 2014.
      Three hundred and eighty-two patients underwent culprit-only revascularization
      and 220 underwent staged complete revascularization. Primary end points were a
      composite of cardiac mortality or nonfatal reinfarction. RESULTS: The mean
      duration of follow-up was 35 months (12-71 months). Following multivariate
      analysis, staged complete revascularization was associated with a lower rate of
      the composite of cardiac mortality or nonfatal reinfarction [HR: 0.430, 95 % CI:
      0.197-0.940, P = 0.034] and unplanned repeat revascularization [HR: 0.343, 95 %
      CI: 0.166-0.708, P = 0.004] compared with culprit-only revascularization.
      CONCLUSIONS: Compared with culprit-only revascularization, staged complete
      revascularization significantly reduced the rate of the composite of cardiac
      mortality or nonfatal reinfarction, and the need for unplanned repeat
      revascularization.

PMID- 27716076
TI  - Smartphone use habits of anesthesia providers during anesthetized patient care: a
      survey from Turkey.
AB  - BACKGROUND: Smartphones are used in many areas of anesthesia practice. However,
      recent editorial articles have expressed concerns about smartphone uses in the
      operating room for non-medical purposes. We performed a survey to learn about the
      smartphone use habits and views of Turkish anesthesia providers. METHODS: A
      questionnaire consisting of 14 questions about smartphone use habits during
      anesthesia care was sent anesthesia providers. RESULTS: In November-December
      2015, a total of 955 participants answered our survey with 93.7 % of respondents
      responding that they used smartphones during the anesthetized patient care. Phone
      calls (65.4 %), messaging (46.4 %), social media (35.3 %), and surfing the
      internet (33.7 %) were the most common purposes. However, 96.7 % of respondents
      indicated that smartphones were either never or seldom used during critical
      stages of anesthesia. Most respondents (87.3 %) stated that they were never
      distracted because of smartphone use; however, 41 % had witnessed their collagues
      in such a situation at least once. CONCLUSIONS: According to the results of the
      survey, smartphones are used in the operating room often for non-medical
      purposes. Distraction remains a concern but evidence-based data on whether
      restrictions to smartphone use are required are not yet available.

PMID- 27716077
TI  - Changes in plasma ghrelin and leptin levels in patients with peptic ulcer and
      gastritis following eradication of Helicobacter pylori infection.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) infection and eradication therapy
      have been known to influence gastric ghrelin and leptin secretion, which may lead
      to weight gain. However, the exact relationship between plasma ghrelin/leptin
      levels and H. pylori infection has remained controversial. The aim of this study
      was to investigate plasma ghrelin and leptin levels in H. pylori-positive and 
      negative patients, to compare the two levels of the hormones before and after H.
      pylori eradication, and to examine the correlation between body mass index (BMI)
      and active ghrelin or leptin levels, as well as that between atrophic pattern and
      active ghrelin or leptin levels. METHODS: Seventy-two H. pylori-positive patients
      who underwent upper gastrointestinal endoscopy, 46 diagnosed as having peptic
      ulcer and 26 as atrophic gastritis, were enrolled. Control samples were obtained
      from 15 healthy H. pylori-negative volunteers. The extent of atrophic change of
      the gastric mucosa was assessed endoscopically. Body weight was measured and
      blood was collected before and 12 weeks after H. pylori eradication therapy.
      Blood samples were taken between 8 and 10 AM after an overnight fast. RESULTS:
      Plasma ghrelin levels were significantly lower in H. pylori-positive patients
      than in H. pylori-negative patients. In particular, plasma active ghrelin levels
      were significantly lower in patients with gastritis compared with patients with
      peptic ulcer. Plasma ghrelin levels decreased after H. pylori eradication in both
      peptic ulcer and gastritis patients, while plasma leptin levels increased only in
      peptic ulcer patients. Plasma leptin levels and BMI were positively correlated,
      and active ghrelin levels and atrophic pattern were weakly negatively correlated
      in peptic ulcer patients. CONCLUSION: H. pylori infection and eradication therapy
      may affect circulating ghrelin/leptin levels. This finding suggests a
      relationship between gastric mucosal injury induced by H. pylori infection and
      changes in plasma ghrelin and leptin levels.

PMID- 27716078
TI  - A case of asystole from carotid sinus hypersensitivity during patient positioning
      for thyroidectomy.
AB  - BACKGROUND: We present a case of a patient with multinodular goiter disease who
      suffered asystole during head hyperextension for surgical positioning on the
      operational table. CASE PRESENTATION: Manipulation of carotid sinus may trigger
      bradycardia or even asystole even in patients without prior history of carotid
      sinus hypersensitivity. The time proximity between patient positioning and
      asystole, the late responsiveness to atropine, the immediate increase of heart
      rate after head elevation and the lack of any other trigger factor or prior
      history support the hypothesis of carotid sinus syndrome. CONCLUSIONS: Head
      hyperextension during surgical positioning is not only responsible for
      jeopardizing blood flow to spinal cord and brainstem but may trigger reflexes, as
      well, even in patients without prior neck pathology.

PMID- 27716079
TI  - Adjusting for overdispersion in piecewise exponential regression models to
      estimate excess mortality rate in population-based research.
AB  - BACKGROUND: In population-based cancer research, piecewise exponential regression
      models are used to derive adjusted estimates of excess mortality due to cancer
      using the Poisson generalized linear modelling framework. However, the assumption
      that the conditional mean and variance of the rate parameter given the set of
      covariates x i are equal is strong and may fail to account for overdispersion
      given the variability of the rate parameter (the variance exceeds the mean).
      Using an empirical example, we aimed to describe simple methods to test and
      correct for overdispersion. METHODS: We used a regression-based score test for
      overdispersion under the relative survival framework and proposed different
      approaches to correct for overdispersion including a quasi-likelihood, robust
      standard errors estimation, negative binomial regression and flexible piecewise
      modelling. RESULTS: All piecewise exponential regression models showed the
      presence of significant inherent overdispersion (p-value <0.001). However, the
      flexible piecewise exponential model showed the smallest overdispersion parameter
      (3.2 versus 21.3) for non-flexible piecewise exponential models. CONCLUSION: We
      showed that there were no major differences between methods. However, using a
      flexible piecewise regression modelling, with either a quasi-likelihood or robust
      standard errors, was the best approach as it deals with both, overdispersion due
      to model misspecification and true or inherent overdispersion.

PMID- 27716080
TI  - Collagenous colitis presenting as spontaneous perforation in an 80 year old
      woman: Report of a Case.
AB  - BACKGROUND: Perforation of the colon occurring during or shortly following
      colonoscopy or barium enema is a rare complication of collagenous colitis (CC).
      "Spontaneous" perforation in CC, in which no instigating factor is identified, is
      even less common, with only five cases reported to date. We report herein an
      additional case of spontaneous perforation in previously undiagnosed CC and
      review the clinical and pathological features of previously reported cases. CASE
      PRESENTATION: An 80 year old woman presented to the emergency department with
      abdominal pain preceded by approximately one month of frequent non-bloody
      diarrhea. Abdominal CT showed parietal thickening of the colon at the splenic
      flexure with pneumatosis and signs of perforation. Segmental resection was
      performed. Pathologic examination showed the microscopic findings typical of CC
      complicated by several deep ulcers and perforation. One day following discharge
      from hospital abdominal pain and frequent non-bloody diarrhea recurred. The
      patient was managed conservatively and treated with oral budesonide with
      resulting resolution of symptoms. CONCLUSIONS: Spontaneous perforation is a rare
      and serious complication of CC. All patients to date have been female. In
      contrast to procedure-related perforation, which favors the right colon,
      spontaneous perforation in CC has in all cases involved the left colon. Knowledge
      of spontaneous perforation as a potential complication of previously undiagnosed
      CC may be helpful in the evaluation and management of patients presenting with
      colonic perforation, especially those with risk factors for CC.

PMID- 27716081
TI  - Thoracic epidural analgesia reduces gastric microcirculation in the pig.
AB  - BACKGROUND: Thoracic epidural analgesia (TEA) is used for pain relief during and
      after abdominal surgery, but the effect of TEA on the splanchnic microcirculation
      remains debated. We evaluated whether TEA affects splanchnic microcirculation in
      the pig. METHODS: Splanchnic microcirculation was assessed in nine pigs prior to
      and 15 and 30 min after induction of TEA. Regional blood flow was assessed by
      neutron activated microspheres and changes in microcirculation by laser speckle
      contrast imaging (LSCI). RESULTS: As assessed by LSCI 15 min following TEA,
      gastric arteriolar flow decreased by 22 % at the antrum (p = 0.020) and by 19 %
      at the corpus (p = 0.029) of the stomach. In parallel, the microcirculation
      decreased by 19 % at the antrum (p = 0.015) and by 20 % at the corpus (p =
      0.028). Reduced arteriolar flow and microcirculation at the antrum was confirmed
      by a reduction in microsphere assessed regional blood flow 30 min following
      induction of TEA (p = 0.048). These manifestations took place along with a drop
      in systolic blood pressure (p = 0.030), but with no significant change in mean
      arterial pressure, cardiac output, or heart rate. CONCLUSION: The results
      indicate that TEA may have an adverse effect on gastric arteriolar blood flow and
      microcirculation. LSCI is a non-touch technique and displays changes in blood
      flow in real-time and may be important for further evaluation of the concern
      regarding the effect of thoracic epidural anesthesia on gastric microcirculation
      in humans. TRIAL REGISTRATIONS: Not applicable, non-human study.

PMID- 27716083
TI  - Intraoperative echocardiographic delineation of the high take-off coronary ostia
      during an extensive surgical repair of the bicuspid aortic valve and dilated
      sinotubular junction: a case report.
AB  - BACKGROUND: This study reports the efficacy of intraoperative transesophageal
      echocardiography (TEE) for evaluation of high take-off coronary ostia and
      proximal coronary arterial flows as an alternative to preoperative coronary
      angiography. CASE PRESENTATION: In a 65-year old male undergoing the bicuspid
      aortic valve (BAV) repair and the extensive remodeling of dilated sinus and
      tubular junction, and preoperative coronary angiography were unsuccessfully
      completed due to an allergic reaction to the contrast medium. Intraoperative TEE
      by employing various 3-dimensional volume images of coronary ostia and Doppler
      tracings of the coronary arterial flows enabled a thorough pre-procedural
      evaluation of the high take-off coronary arteries and post-procedural evaluation
      by confirming the absence of any compromise in coronary arterial flow.
      CONCLUSION: In the present case, intraoperative application of various TEE
      imaging modalities enabled comprehensive evaluation of high-taking off coronary
      artery, as an alternative to preoperative coronary angiography, in a patient
      undergoing an extensive aortic valve and aortic root repair procedure.

PMID- 27716082
TI  - First do no harm: pain relief for the peripheral venous cannulation of adults, a
      systematic review and network meta-analysis.
AB  - BACKGROUND: Peripheral venous cannulation is an everyday practice in hospitals,
      which many adults find painful. However, anaesthesia for cannulation is usually
      only offered to children. Inadequate pain relief is not only unpleasant for
      patients but may cause anxiety about further treatment and deter patients from
      seeking medical care in the future. The aim of this study is to discover the most
      effective local anaesthetic for adult peripheral venous cannulation and to find
      out how the pain of local anaesthetic application compares with that of
      unattenuated cannulation. METHODS: These aims are addressed through a systematic
      review, network meta-analysis and random-effects meta-analysis. Searching covered
      12 databases including MEDLINE and EMBASE from 1990 to August 2015. The main
      included study design was RCTs. The primary outcome measure is self-reported
      pain, measured on a 100 mm visual analogue scale. RESULTS: The systematic review
      found 37 includable studies, 27 of which were suitable for network meta-analysis
      and two for random-effects meta-analysis. The results of the network meta
      analysis indicate that none of the 17 anaesthetic considered had a very high
      probability of being the most effective when compared to each other; 2 %
      lidocaine had the highest probability (44 %). When the anaesthetics were compared
      to no treatment, the network meta-analysis showed that again 2 % lidocaine was
      estimated to be the most effective (mean difference -25.42 (95 % CI -32.25, 
      18.57). Other members of the 'caine' family were also estimated to be more
      effective than no treatment as were Ametop(r), EMLA(r) and Rapydan(r) patch. The
      meta-analysis compared the pain of anaesthetic application with the unattenuated
      pain of cannulation. This found that all applications of local anaesthetic were
      less painful than cannulation without local anaesthetic. In particular a 1 %
      lidocaine injection was estimated to be -12.97 (95 % CI -15.71, -10.24) points
      (100 mm VAS) less painful than unattenuated cannulation. CONCLUSIONS: The pain of
      peripheral venous cannulation in adults can be successfully treated. The pain of
      application of any local anaesthetic is less than that of unattenuated
      cannulation. Local anaesthetic prior to cannulation should become normal practice
      and a marker of high quality care. PROTOCOL REGISTRATION: The protocol for the
      larger study was registered with PROSPERO no. CRD42012002093 .

PMID- 27716084
TI  - Quinine induced simvastatin toxicity through cytochrome inhibition - a case
      report.
AB  - BACKGROUND: Nocturnal leg cramps are painful, involuntary muscle contractions
      commonly seen in elderly. While mostly harmless, they can severely impair quality
      of life and often disrupt sleep. Adverse drug effects may be responsible for a
      fraction of nocturnal leg cramps but often go unrecognized, resulting in
      additional prescribing intended to deal with adverse effects that might be better
      addressed by reduction, substitution, or discontinuation of the offending agent.
      CASE PRESENTATION: An 87 year old female presented as outpatient in family
      medicine with nocturnal leg cramps which had been present for five years and
      increasingly burdened her quality of life. She had been using quinine 200 mg once
      daily for symptomatic relief but the cramps kept returning with increasing
      intensity. During clinical examination we found neither structural nor
      neurological or metabolic disorders that explained her symptoms. When doing a
      medication analysis, we found that she was taking a statin together with quinine.
      Quinine is a cytochrome P450 isoenzyme 3A4 inhibitor, the very enzyme which is
      involved in the metabolism of most statins. Therefore the use of both substances
      simultaneously increases blood levels of the statin thereby increasing the risk
      of side effects including symptomatic myopathy and myalgia. After discontinuing
      both medications, the patient was, and remained, symptom free. CONCLUSION: This
      case report describes a possible medication interaction that has rarely been
      noted in literature.

PMID- 27716085
TI  - Clinical significance of incidental [18 F]FDG uptake in the gastrointestinal
      tract on PET/CT imaging: a retrospective cohort study.
AB  - BACKGROUND: The frequency and clinically important characteristics of incidental
      (18)F-fluorodeoxyglucose ([18 F]FDG) positron emission tomography (PET) uptake in
      the gastrointestinal tract (GIT) on PET/CT imaging in adults remain elusive.
      METHODS: All PET/CT reports from 1/1/2000 to 12/31/2009 at a single tertiary
      referral center were reviewed; clinical information was obtained from cases with
      incidental (18)F-FDG uptake in the GIT, with follow-up through October, 2012.
      RESULTS: Of the 41,538 PET/CT scans performed during the study period, 303 (0.7
      %) had incidental GIT uptake. The most common indication for the PET/CT order was
      cancer staging (226 cases, 75 %), with 74 % for solid and 26 % for hematologic
      malignancies. Of those with solid malignancy, only 51 (17 %) had known metastatic
      disease. The most common site of GIT uptake was the colon, and of the 240 cases
      with colonic uptake, the most common areas of uptake were cecum (n = 65), sigmoid
      (n = 60), and ascending colon (n = 50). Investigations were pursued for the GIT
      uptake in 147 cases (49 %), whereas 51 % did not undergo additional studies,
      largely due to advanced disease. There were 73 premalignant colonic lesions
      diagnosed in 56 cases (tubular adenoma, n = 36; tubulovillous adenoma with low
      grade dysplasia, n = 27; sessile serrated adenoma, n = 4; tubulovillous adenoma
      with high grade dysplasia, n = 3; villous adenoma, n = 3), and 20 cases with
      newly diagnosed primary colon cancer. All 20 (100 %) patients with malignant
      colonic lesions had a focal pattern of [18 F]FDG uptake. Among cases with a known
      pattern of [18 F]FDG uptake, 98 % of those with premalignant lesions had focal
      [18 F]FDG uptake. Eighteen (90 %) of the cases with newly diagnosed colon cancer
      were not known to have metastatic disease of their primary tumor. Areas of
      incidental uptake in the ascending colon had the greatest chance (42 %) of being
      malignant and premalignant lesions than in any other area. CONCLUSION: Focality
      of uptake is highly sensitive for malignant and premalignant lesions of the GIT.
      In patients without metastatic disease, incidental focal [18]FDG uptake in the
      GIT on PET/CT imaging warrants further evaluation.

PMID- 27716086
TI  - Association of CD247 (CD3zeta) gene polymorphisms with T1D and AITD in the
      population of northern Sweden.
AB  - BACKGROUND: T1D and AITD are autoimmune disorders commonly occurring in the same
      family and even in the same individual. The genetic contribution to these
      disorders is complex making uncovering of susceptibility genes very challenging.
      The general aim of this study was to identify loci and genes contributing to
      T1D/AITD susceptibility. Our strategy was to perform linkage and association
      studies in the relatively genetically homogenous population of northern Sweden.
      We performed a GWLS to find genomic regions linked to T1D/AITD in families from
      northern Sweden and we performed an association study in the families to test for
      association between T1D/AITD and variants in previously published candidate genes
      as well as a novel candidate gene, CD247. METHODS: DNA prepared from 459
      individuals was used to perform a linkage and an association study. The ABI PRISM
      Linkage Mapping Set v2.5MD10 was employed for an initial 10-cM GWLS, and
      additional markers were added for fine mapping. Merlin was used for linkage
      calculations. For the association analysis, a GoldenGate Custom Panel from
      Illumina containing 79 SNPs of interest was used and FBAT was used for
      association calculations. RESULTS: Our study revealed linkage to two previously
      identified chromosomal regions, 4q25 and 6p22, as well as to a novel chromosomal
      region, 1q23. The association study replicated association to PTPN22, HLA-DRB1,
      INS, IFIH1, CTLA4 and C12orf30. Evidence in favor of association was also found
      for SNPs in the novel susceptibility gene CD247. CONCLUSIONS: Several risk loci
      for T1D/AITD identified in published association studies were replicated in a
      family material, of modest size, from northern Sweden. This provides evidence
      that these loci confer disease susceptibility in this population and emphasizes
      that small to intermediate sized family studies in this population can be used in
      a cost-effective manner for the search of genes involved in complex diseases. The
      linkage study revealed a chromosomal region in which a novel T1D/AITD
      susceptibility gene, CD247, is located. The association study showed association
      between T1D/AITD and several variants in this gene. These results suggests that
      common susceptibility genes act in concert with variants of CD247 to generate
      genetic risk for T1D/AITD in this population.

PMID- 27716087
TI  - Small dense low-density lipoprotein cholesterol was associated with future
      cardiovascular events in chronic kidney disease patients.
AB  - BACKGROUND: Cardiovascular disease (CVD) is often comorbid with chronic kidney
      disease (CKD). Small low-density lipoprotein cholesterol (sdLDL-C) has also been
      found to increase risk for CVD. The goal of the present study was to determine
      the nature of the relationship between sdLDL-C concentration and CVD in patients
      with CKD. METHODS: One-hundred and forty-five subjects (113 men and 32 women)
      with CKD (Stage 3 and Stage 4) participated this retrospective study. The
      concentration of sdLDL-C was measured in samples from 145 CKD patients between
      2010 and 2012 during a four-year follow-up period. RESULTS: A total of eight
      fatal cardiovascular events (CVs) and 46 nonfatal CVs were registered in the four
      year follow-up period. Multivariate Cox regression analysis showed that sdLDL-C
      [1.278, 95 % (1.019-1.598)] and sdLDL-C/LDL-C [2.456, 95 % (1.421-15.784)], at
      final observation, were independent risks of CVs. A Kaplan-Meier survival
      analysis showed that patients with sdLDL-C >38 mg/dl (logrank: 4.375, P = 0.037),
      and sdLDL-C/LDL-C ratio >0.3 levels (logrank: 11.94, P = 0.018) were at increased
      risk for CVs. CONCLUSION: The results of this study indicated that for patients
      suffering CKD, a significant relationship exists between an elevated sdLDL-C
      concentration and the risk of cardiovascular disease.

PMID- 27716088
TI  - eRegistries: indicators for the WHO Essential Interventions for reproductive,
      maternal, newborn and child health.
AB  - BACKGROUND: Electronic health registries - eRegistries - can systematically
      collect relevant information at the point of care for reproductive, maternal,
      newborn and child health (RMNCH). However, a suite of process and outcome
      indicators is needed for RMNCH to monitor care and to ensure comparability
      between settings. Here we report on the assessment of current global indicators
      and the development of a suite of indicators for the WHO Essential Interventions
      for use at various levels of health care systems nationally and globally.
      METHODS: Currently available indicators from both household and facility surveys
      were collated through publicly available global databases and respective survey
      instruments. We then developed a suite of potential indicators and associated
      data points for the 45 WHO Essential Interventions spanning preconception to
      newborn care. Four types of performance indicators were identified (where
      applicable): process (i.e. coverage) and outcome (i.e. impact) indicators for
      both screening and treatment/prevention. Indicators were evaluated by an
      international expert panel against the eRegistries indicator evaluation criteria
      and further refined based on feedback by the eRegistries technical team. RESULTS:
      Of the 45 WHO Essential Interventions, only 16 were addressed in any of the
      household survey data available. A set of 216 potential indicators was developed.
      These indicators were generally evaluated favourably by the panel, but
      difficulties in data ascertainment, including for outcome measures of cause
      specific morbidity and mortality, were frequently reported as barriers to the
      feasibility of indicators. Indicators were refined based on feedback, culminating
      in the final list of 193 total unique indicators: 93 for preconception and
      antenatal care; 53 for childbirth and postpartum care; and 47 for newborn and
      small and ill baby care. CONCLUSIONS: Large gaps exist in the availability of
      information currently collected to support the implementation of the WHO
      Essential Interventions. The development of this suite of indicators can be used
      to support the implementation of eRegistries and other data platforms, to ensure
      that data are utilised to support evidence-based practice, facilitate measurement
      and accountability, and improve maternal and child health outcomes.

PMID- 27716089
TI  - Absence of convincing evidence of Coxiella burnetii infection in Chile: a cross
      sectional serosurvey among healthy adults in four different regions.
AB  - BACKGROUND: Coxiella burnetii is an important zoonotic pathogen of global
      distribution. Still, in most parts of South America including Chile, systematic
      epidemiological data are lacking. The presented study aims to determine the
      seroprevalence of Coxiella burnetii antibodies in healthy adults of four
      different regions in Chile. METHODS: A cross-sectional study was performed, which
      included healthy adults living in rural and urban areas of four cities located in
      different regions in northern, central, and southern Chile. In urban sectors,
      households were chosen by double stratified random sampling, while in rural areas
      convenience sampling was performed. Serum specimens were taken and screened for
      the presence of IgG antibodies against C. burnetii phase II antigen using a
      commercial ELISA kit. Positive and indeterminate results were confirmed by a
      reference laboratory using indirect immunofluorescence assay (IFA). RESULTS: A
      total of 1112 individuals were included. Of those, 8 were positive by ELISA, but
      only one sample was confirmed using IFA. Statistical analysis for population
      freedom from disease revealed a high probability that C. burnetii was absent in
      our study population. CONCLUSION: Our work provides the first epidemiological
      data on human Q fever in Chile indicating either a very low endemicity or the
      absence of this pathogen in the studied areas.

PMID- 27716090
TI  - Seeking order amidst chaos: a systematic review of classification systems for
      causes of stillbirth and neonatal death, 2009-2014.
AB  - BACKGROUND: Each year, about 5.3 million babies die in the perinatal period.
      Understanding of causes of death is critical for prevention, yet there is no
      globally acceptable classification system. Instead, many disparate systems have
      been developed and used. We aimed to identify all systems used or created between
      2009 and 2014, with their key features, including extent of alignment with the
      International Classification of Diseases (ICD) and variation in features by
      region, to inform the World Health Organization's development of a new global
      approach to classifying perinatal deaths. METHODS: A systematic literature review
      (CINAHL, EMBASE, Medline, Global Health, and PubMed) identified published and
      unpublished studies and national reports describing new classification systems or
      modifications of existing systems for causes of perinatal death, or that used or
      tested such systems, between 2009 and 2014. Studies reporting ICD use only were
      excluded. Data were independently double-extracted (except from non-English
      publications). Subgroup analyses explored variation by extent and region.
      RESULTS: Eighty-one systems were identified as new, modifications of existing
      systems, or having been used between 2009 and 2014, with an average of ten
      systems created/modified each year. Systems had widely varying characteristics:
      (i) comprehensiveness (40 systems classified both stillbirths and neonatal
      deaths); (ii) extent of use (systems were created in 28 countries and used in 40;
      17 were created for national use; 27 were widely used); (iii) accessibility
      (three systems available in e-format); (iv) underlying cause of death (64 systems
      required a single cause of death); (v) reliability (10 systems tested for
      reliability, with overall Kappa scores ranging from .35-.93); and (vi) ICD
      alignment (17 systems used ICD codes). Regional databases were not searched, so
      system numbers may be underestimated. Some non-differential misclassification of
      systems was possible. CONCLUSIONS: The plethora of systems in use, and continuing
      system development, hamper international efforts to improve understanding of
      causes of death. Recognition of the features of currently used systems, combined
      with a better understanding of the drivers of continued system creation, may help
      the development of a truly effective global system.

PMID- 27716091
TI  - Entomological efficacy of durable wall lining with reduced wall surface coverage
      for strengthening visceral leishmaniasis vector control in Bangladesh, India and
      Nepal.
AB  - BACKGROUND: New methods for controlling sand fly are highly desired by the
      Visceral Leishmaniasis (VL) elimination program of Bangladesh, India and Nepal
      for its consolidation and maintenance phases. To support the program we
      investigated safety, efficacy and cost of Durable Wall Lining to control sand
      fly. METHODS: This multicentre randomized controlled study in Bangladesh, India
      and Nepal included randomized two intervention clusters and one control cluster.
      Each cluster had 50 households except full wall surface coverage (DWL-FWSC)
      cluster in Nepal which had 46 households. Ten of 50 households were randomly
      selected for entomological activities  except India where it was 6 households.
      Interventions were DWL-FWSC and reduced wall surface coverage (DWL-RWSC) with DWL
      which covers 1.8 m and 1.5 m height from floor respectively. Efficacy was
      measured by reduction in sand fly density by intervention and sand fly mortality
      assessment by the WHO cone bioassay test at 1 month after intervention. Trained
      field research assistants interviewed household heads for socio-demographic
      information, knowledge and practice about VL, vector control, and for their
      experience following the intervention. Cost data was collected using cost data
      collection tool which was designed for this study. Statistical analysis included
      difference-in-differences estimate, bivariate analysis, Poisson regression model
      and incremental cost-efficacy ratio calculation. RESULTS: Mean sand fly density
      reduction by DWL-FWSC and DWL-RWSC was respectively -4.96 (95 % CI, -4.54, -5.38)
      and -5.38 (95 % CI, -4.89, -5.88). The sand fly density reduction attributed by
      both the interventions were statistically significant after adjusting for
      covariates (IRR = 0.277, p < 0.001 for DWL-RWSC and IRR = 0.371, p < 0.001 for
      DWL-FWSC). The efficacy of DWL-RWSC and DWL-FWSC on sand fly density reduction
      was statistically comparable (p = 0.214). The acceptability of both interventions
      was high. Transient burning sensations, flash on face and itching were most
      common adverse events and were observed mostly in Indian site. There was no
      serious adverse event. DWL-RWSC is cost-saving compared to DWL-FWSC. The
      incremental cost-efficacy ratio was -6.36, where DWL-RWSC dominates DWL-FWSC.
      CONCLUSIONS: DWL-RWSC intervention is safe, efficacious, cost-saving and cost
      effective in reducing indoor sand fly density. The VL elimination program in the
      Indian sub-continent may consider DWL-RWSC for sand fly control for its
      consolidation and maintenance phases.

PMID- 27716092
TI  - A deformable template method for describing and averaging the anatomical
      variation of the human nasal cavity.
AB  - BACKGROUND: Understanding airflow through human airways is of importance in drug
      delivery and development of assisted breathing methods. In this work, we focus on
      development of a new method to obtain an averaged upper airway geometry from
      computed tomography (CT) scans of many individuals. This geometry can be used for
      air flow simulation. We examine the geometry resulting from a data set consisting
      of 26 airway scans. The methods used to achieve this include nasal cavity
      segmentation and a deformable template matching procedure. METHODS: The method
      uses CT scans of the nasal cavity of individuals to obtain a segmented mesh, and
      coronal cross-sections of this segmented mesh are taken. The cross-sections are
      processed to extract the nasal cavity, and then thinned ('skeletonized')
      representations of the airways are computed. A reference template is then
      deformed such that it lies on this thinned representation. The average of these
      deformations is used to obtain the average geometry. Our procedure tolerates a
      wider variety of nasal cavity geometries than earlier methods. RESULTS: To assess
      the averaging method, key landmark points on each of the input scans as well as
      the output average geometry are located and compared with one another, showing
      good agreement. In addition, the cross-sectional area (CSA) profile of the nasal
      cavities of the input scans and average geometry are also computed, showing that
      the CSA of the average model falls within the variation of the population.
      CONCLUSIONS: The use of a deformable template method for aligning and averaging
      the nasal cavity provides an improved, detailed geometry that is unavailable
      without using deformation.

PMID- 27716094
TI  - Modulation of renal oxygenation and perfusion in rat kidney monitored by
      quantitative diffusion and blood oxygen level dependent magnetic resonance
      imaging on a clinical 1.5T platform.
AB  - BACKGROUND: To investigate the combined use of intravoxel incoherent motion
      (IVIM) diffusion-weighted (DW) and blood oxygen level dependent (BOLD) magnetic
      resonance imaging (MRI) to assess rat renal function using a 1.5T clinical
      platform. METHODS: Multiple b-value DW and BOLD MR images were acquired from
      adult rats using a parallel clinical coil arrangement, enabling quantitation of
      the apparent diffusion coefficient (ADC), IVIM-derived diffusion coefficient (D),
      pseudodiffusion coefficient (D*) and perfusion fraction (f), and the transverse
      relaxation time T2*, for whole kidney, renal cortex, and medulla. Following the
      acquisition of two baseline datasets to assess measurement repeatability, images
      were acquired following i.v. administration of hydralazine, furosemide, or
      angiotensin II for up to 40 min. RESULTS: Excellent repeatability (CoV <10 %) was
      observed for ADC, D, f and T2* measured over the whole kidney. Hydralazine
      induced a marked and significant (p < 0.05) reduction in whole kidney ADC, D, and
      T2*, and a significant (p < 0.05) increase in D* and f. Furosemide significantly
      (p < 0.05) increased whole kidney ADC, D, and T2*. A more variable response to
      angiotensin II was determined, with a significant (p < 0.05) increase in medulla
      D* and significant (p < 0.05) reduction in whole kidney T2* established.
      CONCLUSIONS: Multiparametric MRI, incorporating quantitation of IVIM DWI and BOLD
      biomarkers and performed on a clinical platform, can be used to monitor the acute
      effects of vascular and tubular modulating drugs on rat kidney function in vivo.
      Clinical adoption of such functional imaging biomarkers can potentially inform on
      treatment effects in patients with renal dysfunction.

PMID- 27716093
TI  - Effectiveness and safety of generic version of abacavir/lamivudine and efavirenz
      in treatment naive HIV-infected patients: a nonrandomized, open-label, phase IV
      study in Cali-Colombia, 2011-2012.
AB  - BACKGROUND: Generic drug policies are often associated with concerns about the
      quality and effectiveness of these products. Phase IV clinical trials may be a
      suitable design to assess the effectiveness and safety of generic drugs. The
      objective of this study was to describe the effectiveness and the safety of the
      generic abacavir/lamivudine and efavirenz in treatment-naive HIV-infected
      patients. METHODS: A monocentric, nonrandomized, open-label, phase IV study in
      treatment naive HIV-infected patients 18 years or older with indication to
      receive abacavir/lamivudine and efavirenz were recruited from a program that
      provides comprehensive outpatient consultation and continuing care. The primary
      end-point was to achieve viral load <40 copies/mL at 12 months after baseline to
      assess effectiveness. Secondary end-point of the study were 1) to asses
      increasing in T-CD4 lymphocytes levels as accompaniment to asses effectiveness,
      and 2) to assess both gastrointestinal, skin, and central nervous system
      symptoms, and lipid profile, cardiovascular risk, renal, and hepatic function as
      safety profile. Data were determined at baseline, 3, 6, and 12 months. Close
      clinical monitoring and pharmaceutical care were used for data collection.
      Wilcoxon matched-pairs signed-rank test was used to compare proportions or
      medians. RESULTS: Sixty patients were invited to participate in the study; 42
      were enrolled and 33 completed the follow-up. Of the nine patients excluded from
      the study, only one was withdrawn due to adverse events. At 12 months, 31 of 42
      patients (73.8 % in intention-to-treat analysis) achieved a viral load of HIV1
      RNA <40 copies/mL. There was a significant increase (172 cells/mm3) in the median
      for CD4 T lymphocyte count. The adverse events were mild and met the safety
      profile for this antiretroviral regimen, mainly of central nervous system
      symptoms, skin rash, lipid abnormalities, and an increase of 2 % in the median of
      the percentage of cardiovascular risk. CONCLUSIONS: The clinical outcomes of
      generic version of abacavir/lamivudine and efavirenz in HIV treatment naive
      patients showed the expected safety and effectiveness profile of proprietary ARV
      drugs. TRIAL REGISTRATION: Registro Publico Cubano de Ensayos Clinicos (RPCEC)
      ID: RPCEC00000202 . Registered 19 November 2015.

PMID- 27716095
TI  - For whom is a health-promoting intervention effective? Predictive factors for
      performing activities of daily living independently.
AB  - BACKGROUND: Health-promoting interventions tailored to support older persons to
      remain in their homes, so-called "ageing in place" is important for supporting or
      improving their health. The health-promoting programme "Elderly Persons in the
      Risk Zone," (EPRZ) was set up for this purpose and has shown positive results for
      maintaining independence in activities of daily living for older persons 80 years
      and above at 1- and 2 year follow-ups. The aim of this study was to explore
      factors for maintaining independence in the EPRZ health-promoting programme.
      METHODS: Total of 459 participants in the original trial was included in the
      analysis; 345 in the programme arm and 114 in the control arm. Thirteen
      variables, including demographic, health, and programme-specific indicators, were
      chosen as predictors for independence of activities of daily living. Logistic
      regression was performed separately for participants in the health promotion
      programme and in the control arm. RESULTS: In the programme arm, being younger,
      living alone and self-rated lack of tiredness in performing mobility activities
      predicted a positive effect of independence in activities of daily living at 1
      year follow-up (odds ratio [OR] 1.18, 1.73, 3.02) and 2-year, (OR 1.13, 2.01,
      2.02). In the control arm, being less frail was the only predictor at 1-year
      follow up (OR 1.6 1.09, 2.4); no variables predicted the outcome at the 2-year
      follow-up. CONCLUSIONS: Older persons living alone - as a risk of ill health -
      should be especially recognized and offered an opportunity to participate in
      health-promoting programmes such as "Elderly Persons in the Risk Zone". Further,
      screening for subjective frailty could form an advantageous guiding principle to
      target the right population when deciding to whom health-promoting intervention
      should be offered. TRIAL REGISTRATION: The original clinical trial was registered
      at ClinicalTrials.gov. Identifier: NCT00877058 , April 6, 2009.

PMID- 27716096
TI  - The effect of intramuscular interferon beta-1a on spinal cord volume in relapsing
      remitting multiple sclerosis.
AB  - BACKGROUND: Spinal cord atrophy occurs early in multiple sclerosis (MS) and
      impacts disability. The therapeutic effect of interferon beta-1a (IFNbeta-1a) on
      spinal cord atrophy in patients with relapsing-remitting (RR) MS has not been
      explored. METHODS: We retrospectively identified 16 consecutive patients
      receiving weekly intramuscular IFNbeta-1a for 2 years [baseline age (mean +/- SD)
      47.7 +/- 7.5 years, Expanded Disability Status Scale score median (range) 1.5 (0
      2.5), timed 25-foot walk 4.6 +/- 0.7 seconds; time on treatment 68.3 +/- 59.9
      months] and 11 sex- and age-matched normal controls (NC). The spinal cord was
      imaged at baseline, 1 and 2 years later with 3T MRI. C1-C5 spinal cord volume was
      measured by an active surface method, from which normalized spinal cord area
      (SCA) was calculated. RESULTS: SCA showed no change in the MS or NC group over 2
      years [mean annualized difference (95 % CI) MS: -0.604 mm2 (-1.352, 0.144), p =
      0.106; NC: -0.360 mm2 (-1.576, 0.855), p = 0.524]. Between group analysis
      indicated no differences in on-study SCA change [MS vs. NC; year 1 vs. baseline,
      mean annualized difference (95 % CI) 0.400 mm2 (-3.350, 2.549), p = 0.780; year 2
      vs. year 1: -1.196 mm2 (-0.875, 3.266), p = 0.245; year 2 vs. baseline -0.243 mm2
      (-1.120, 1.607), p = 0.712]. CONCLUSION: Established IFNbeta-1a therapy was not
      associated with ongoing spinal cord atrophy or any difference in the rate of
      spinal cord volume change in RRMS compared to NC over 2 years. These results may
      reflect a treatment effect. However, due to sample size and study design, these
      results should be considered preliminary and await confirmation.

PMID- 27716097
TI  - The impact of paclitaxel and carboplatin chemotherapy on the autonomous nervous
      system of patients with ovarian cancer.
AB  - BACKGROUND: Paclitaxel-based regimens are frequently associated with the
      development of peripheral neuropathy. The autonomous nervous system (ANS)
      effects, however, of this chemotherapeutic agent remain unexplored. METHODS: We
      investigated a group of 31 female patients with ovarian cancer receiving
      treatment with paclitaxel and carboplatin, as well as a group of 16 healthy age-
      and gender-matched healthy volunteers. All study participants completed a
      questionnaire and were assessed neurophysiologically at three time points
      (baseline, 3-4 months and 6-8 months following the onset of chemotherapy). The
      evaluation of the ANS included assessment of the adrenergic cardiovascular
      function (orthostatic hypotension-OH), parasympathetic heart innervation (30/15
      ratio) and sympathetic skin response (SSR). RESULTS: At the 3-4 months ANS
      assessment, 19.2 % of the patients had systolic OH and the same percentage had
      diastolic OH, but at the 6-8 months evaluation no patient had systolic OH and
      only 13.8 % had diastolic OH. The values of the 30/15 ratio were significantly
      reduced at both time points, whereas the SSR was not affected. CONCLUSIONS:
      Combined paclitaxel and carboplatin chemotherapy is associated with significant
      effects on the parasympathetic heart innervation and occasionally with effects on
      the adrenergic cardiovascular reaction. The SSR remained unaffected. Physicians
      should be alert to the possibility of these treatment-emergent side effects, so
      as to monitor ANS parameters and introduce treatment modifications accordingly.
      Our findings however, should be validated in larger cohorts.

PMID- 27716098
TI  - Anxiety and depression symptoms among caregivers of care-recipients with
      subjective cognitive decline and cognitive impairment.
AB  - BACKGROUND: Caregivers of care-recipients with mild cognitive impairment (MCI) or
      dementia experience high caregiver burden; however, the psychiatric burden of
      caregivers of care-recipients with subjective cognitive decline (SCD) has not
      been investigated. We aimed to explore the prevalence of and risk factors for
      anxiety and depression symptoms among the caregivers of care-recipients with SCD
      and cognitive impairment. METHODS: The Hospital Anxiety and Depression Scale
      (HADS) was used to examine the anxiety and depression symptoms among the
      caregivers of 343 care-recipients (84 with SCD, 120 with MCI and 139 with
      dementia) treated at the Memory Clinic of Huashan Hospital in Shanghai, China
      from May 2012 to October 2014. A logistic regression was used to explore the
      factors associated with caregiver's anxiety and depression symptoms. RESULTS: In
      total, 26.5 % of caregivers had anxiety symptoms, and 22.4 % had depression
      symptoms. Totals of 17.9, 30.0 and 28.8 % of caregivers of care-recipients with
      SCD, MCI or dementia, respectively, had anxiety symptoms (P = 0.1140), whereas
      22.6, 24.2 and 20.9 %, respectively, had depression symptoms (P = 0.8165). The
      risk factors for caregiver's anxiety symptoms were increased caregiver age as
      well as having care-recipients who were male, had higher Cohen Mansfield
      Agitation Inventory (CMAI) scores, and higher Geriatric Depression Scale (GDS)
      scores. The risk factors for caregiver's depression symptoms were increased
      caregiver age as well as caring for care-recipients with MCI or SCD, those with
      lower Toronto Empathy Questionnaire (TEQ) scores, and those with higher GDS
      scores. CONCLUSIONS: Caregivers of care-recipients with SCD showed the same level
      of depression symptoms as those of care-recipients with MCI. Caregiver's
      depression and anxiety symptoms were associated with their care-recipients'
      psychiatric and behavioral syndromes.

PMID- 27716099
TI  - Prevalence of intestinal parasitic infections and associated risk factors among
      pregnant women attending antenatal care center at Felege Hiwot Referral Hospital,
      northwest Ethiopia.
AB  - BACKGROUND: Parasitic infections affect tens of millions of pregnant women
      worldwide, and directly or indirectly lead to a spectrum of adverse maternal and
      fetal/placental effects. The objective of this study was to assess the prevalence
      of intestinal parasite infections and associated risk factors among pregnant
      women attending antenatal care center in Felege Hiwot Referral Hospital, Bahir
      Dar city, northwest Ethiopia. METHODS: A cross-sectional hospital based study was
      conducted from November 2013 to January 2014 among 384 pregnant women. Stool
      samples were examined for the presence of trophozoites, cysts, oocysts, and ova
      using direct, formal-ether sedimentation, and modified Ziehl-Neelsen techniques.
      RESULTS: An overall prevalence of 31.5 % intestinal parasite infections was
      recorded. Eight different species of intestinal parasites were found: two
      protozoan and six helminth species. The highest prevalence was due to Giardia
      lamblia (13.3 %) followed by Entamoeba histolytica/dispar (7.8 %), hookworm (5.5
      %), Ascaris lumbricoides (2.9 %), Schistosoma mansoni (2.9 %), Strongyloides
      stercoralis (1.6 %), Taenia spp. (0.8 %), and Hymenolepis nana (0.3 %).
      CONCLUSIONS: A relatively high prevalence of intestinal parasite infections was
      observed among pregnant women. Routine stool examination and provision of health
      education are required for early medical intervention that would affect the
      pregnant mothers and their foetuses.

PMID- 27716100
TI  - Temporal trends of beta-haemolytic streptococcal osteoarticular infections in
      western Norway.
AB  - BACKGROUND: Beta-haemolytic streptococci are important contributors to the global
      burden of osteoarticular infections (OAI). Knowledge on the disease traits
      specific for streptococcal OAI, however, remains scarce. We wished to explore
      temporal trends of OAI caused by Group A Streptococci (GAS), Group B Streptococci
      (GBS) and Group C and G Streptococci (GCGS), and furthermore, to describe the
      associated host and pathogen characteristics. METHODS: All cases of
      microbiologically verified beta-haemolytic streptococcal OAI in Health Region
      Bergen, Norway, in the period 1999-2013 were retrospectively identified. Clinical
      data were extracted from medical records. Microbial isolates were submitted to
      antibiotic susceptibility testing and molecular typing. RESULTS: A total of 24
      GAS, 45 GBS and 42 GCGS acute OAI were identified. The cumulative incidence of
      GCGS OAI, but not GAS or GBS OAI, increased significantly from the first to the
      last 5-year period (IRR 5.7, p = 0.0003), with the annual incidence peaking at
      1.9/100 000 in 2013. GAS OAI generally produced the most acute and severe
      clinical presentation, whereas GBS and GCGS predominantly affected the elderly,
      and were significantly associated with the presence of host risk factors of
      systemic and focal origin, respectively. CONCLUSIONS: We found a significantly
      increasing incidence of GCGS OAI, likely related to the presence of host
      susceptibility factors, including prosthetic material and pre-existing joint
      disease. With an increasing application of therapeutic and diagnostic bone and
      joint procedures, the rising trend of OAI caused by GCGS is likely to continue.
      Sustained epidemiological attentiveness to GCGS seems warranted.

PMID- 27716101
TI  - Factors associated with clinical outcome in 25 patients with avian influenza A
      (H7N9) infection in Guangzhou, China.
AB  - BACKGROUND: Guangzhou reported its first laboratory-confirmed case of influenza A
      (H7N9) on January 10, 2014. A total of 25 cases were reported from the first wave
      of the epidemic until April 8, 2014. The fatality rate was much higher than in
      previous reports. The objective of the current work was to describe the clinical
      and epidemiological characteristics of A (H7N9) patients in Guangzhou and explore
      possible reasons for the high fatality rate. METHODS: Clinical and
      epidemiological information regarding A (H7N9) cases in Guangzhou was collected
      through review of medical records and field research. Data regarding clinical and
      laboratory features, treatment, and outcomes were extracted. RESULTS: Of the 25
      patients, 84 % (21/25) had one or more underlying diseases. Fifteen patients
      (60.0 %) developed moderate to severe acute respiratory distress syndrome (ARDS),
      and 14 (56 %) died of the ARDS or multiorgan failure. Patients with longer delay
      between onset of illness and initiation of oseltamivir treatment were more likely
      to develop ARDS. Elevated C-creative protein, aspartate aminotransferase,
      creatine kinase, and lymphocytopenia predicted a higher risk of developing ARDS.
      CONCLUSIONS: The presence of underlying diseases and clinical complications
      predicted poor clinical outcome. Early oseltamivir treatment was associated with
      a reduced risk of developing ARDS.

PMID- 27716102
TI  - Antimicrobial susceptibility testing in predicting the presence of carbapenemase
      genes in Enterobacteriaceae in South Africa.
AB  - BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) is a concern in South
      Africa and worldwide. It is therefore important that these organisms be
      accurately identified for infection prevention control purposes. METHOD: In this
      study 1193 suspected CREs from 46 laboratories from seven provinces in South
      Africa were assessed to confirm the prevalence of carbapenemase genes from our
      referral diagnostic isolates for the period 2012 to 2015. We compared the
      antimicrobial susceptibility testing method used in the reference laboratory to
      the polymerase chain reaction (PCR) which is used as the gold standard. Organism
      identification and antimicrobial susceptibility testing were performed using
      automated systems and DNA was extracted using a crude boiling method. The
      presence of carbapenemase-producing genes (bla NDM, bla KPC, bla OXA-48&variants,
      bla GES, bla IMP and bla VIM) was screened for using a multiplex real-time PCR.
      RESULTS: Sixty-eight percent (n = 812) of the isolates harboured a carbapenemase
      producing gene; the three most common genes included: bla NDM, bla OXA
      48&variants and bla VIM. Majority of the carbapenemase producing
      Enterobacteriaceae (CPE) isolates were Klebsiella species (71 %). The
      Microscan(r) Walkaway system used for the screening of carbapenemase production
      was 98 % sensitive with a minimal inhibitory concentration (MIC) breakpoint of
      less than 0.5 as susceptible for ertapenem and a low specificity (13 %).
      CONCLUSION: From this study we can conclude that carbapenemase-producing
      Enterobacteriaceae is increasing in South Africa and the use of phenotypic
      methods for detection of CPEs showed good sensitivity but lacked specificity.

PMID- 27716104
TI  - Does directly observed therapy improve tuberculosis treatment? More evidence is
      needed to guide tuberculosis policy.
AB  - BACKGROUND: Tuberculosis (TB) now ranks alongside HIV as the leading infectious
      disease cause of death worldwide and incurs a global economic burden of over $12
      billion annually. Directly observed therapy (DOT) recommends that TB patients
      complete the course of treatment under direct observation of a treatment
      supporter who is trained and overseen by health services to ensure that patients
      take their drugs as scheduled. Though the current WHO End TB Strategy does not
      mention DOT, only "supportive treatment supervision by treatment partners", many
      TB programs still use it despite the fact that the has not been demonstrated to
      be statistically significantly superior to self-administered treatment in
      ensuring treatment success or cure. DISCUSSION: DOT is designed to promote proper
      adherence to the full course of drug therapy in order to improve patient outcomes
      and prevent the development of drug resistance. Yet over 8 billion dollars is
      spent on TB treatment each year and thousands undergo DOT for all or part of
      their course of treatment, despite the absence of rigorous evidence supporting
      the superior effectiveness of DOT over self-administration for achieving drug
      susceptible TB (DS-TB) cure. Moreover, the DOT component burdens patients with
      financial and opportunity costs, and the potential for intensified stigma. To
      rigorously evaluate the effectiveness of DOT and identify the essential
      contributors to both successful treatment and minimized patient burden, we call
      for a pragmatic experimental trial conducted in real-world program settings, the
      gold standard for evidence-based health policy decisions. It is time to invest in
      the rigorous evaluation of DOT and reevaluate the DOT requirement for TB
      treatment worldwide. Rigorously evaluating the choice of treatment supporter, the
      frequency of health care worker contact and the development of new educational
      materials in a real-world setting would build the evidence base to inform the
      optimal design of TB treatment protocol. Implementing a more patient-centered
      approach may be a wise reallocation of resources to raise TB cure rates, prevent
      relapse, and minimize the emergence of drug resistance. Maintaining the status
      quo in the absence of rigorous supportive evidence may diminish the effectiveness
      of TB control policies in the long run.

PMID- 27716103
TI  - Root morphology and seed and leaf ionomic traits in a Brassica napus L. diversity
      panel show wide phenotypic variation and are characteristic of crop habit.
AB  - BACKGROUND: Mineral nutrient uptake and utilisation by plants are controlled by
      many traits relating to root morphology, ion transport, sequestration and
      translocation. The aims of this study were to determine the phenotypic diversity
      in root morphology and leaf and seed mineral composition of a polyploid crop
      species, Brassica napus L., and how these traits relate to crop habit. Traits
      were quantified in a diversity panel of up to 387 genotypes: 163 winter, 127
      spring, and seven semiwinter oilseed rape (OSR) habits, 35 swede, 15 winter
      fodder, and 40 exotic/unspecified habits. Root traits of 14 d old seedlings were
      measured in a 'pouch and wick' system (n = ~24 replicates per genotype). The
      mineral composition of 3-6 rosette-stage leaves, and mature seeds, was determined
      on compost-grown plants from a designed experiment (n = 5) by inductively coupled
      plasma-mass spectrometry (ICP-MS). RESULTS: Seed size explained a large
      proportion of the variation in root length. Winter OSR and fodder habits had
      longer primary and lateral roots than spring OSR habits, with generally lower
      mineral concentrations. A comparison of the ratios of elements in leaf and seed
      parts revealed differences in translocation processes between crop habits,
      including those likely to be associated with crop-selection for OSR seeds with
      lower sulphur-containing glucosinolates. Combining root, leaf and seed traits in
      a discriminant analysis provided the most accurate characterisation of crop
      habit, illustrating the interdependence of plant tissues. CONCLUSIONS: High
      throughput morphological and composition phenotyping reveals complex
      interrelationships between mineral acquisition and accumulation linked to genetic
      control within and between crop types (habits) in B. napus. Despite its recent
      genetic ancestry (<10 ky), root morphology, and leaf and seed composition traits
      could potentially be used in crop improvement, if suitable markers can be
      identified and if these correspond with suitable agronomy and quality traits.

PMID- 27716105
TI  - Prevalence and factors associated with use of herbal medicines during pregnancy
      among women attending postnatal clinics in Gulu district, Northern Uganda.
AB  - BACKGROUND: According to World Health Organization (WHO) estimates, 80 % of the
      population living in rural areas in developing countries depends on traditional
      medicine for their health needs, including use during pregnancy. Despite the fact
      that knowledge of potential side effects of many herbal medicines in pregnancy is
      limited and that some herbal products may be teratogenic, data on the extent of
      use of herbal medicines by women during pregnancy in the study setting is largely
      unknown. We determined the prevalence and factors associated with herbal medicine
      use during pregnancy among women attending postnatal clinics in Gulu district,
      Northern Uganda. METHODS: This was a descriptive cross-sectional study which
      involved 383 women attending postnatal care across four sites in Gulu district
      using quantitative and qualitative methods of data collection. A structured
      questionnaire was used to collect quantitative data while qualitative data were
      obtained using focus group discussions and key informant interviews. The
      selection of the study participants was by systematic sampling and the main
      outcome variable was the proportion of mothers who used herbal medicine.
      Quantitative data was coded and entered into a computerized database using
      Epidata 3.1. Analysis was done using Statistical Package for Social Scientists
      version 13, while thematic analysis was used for qualitative data. RESULTS: The
      prevalence of herbal medicines use during the current pregnancy was 20 %
      (78/383), and was commonly used in the second 23 % (18/78) and third 21 % (16/78)
      trimesters. The factors significantly associated with use of herbal medicines
      during pregnancy were perception (OR 2.18, CI 1.02-4.66), and having ever used
      herbal medicines during previous pregnancy (OR 2.51, CI 1.21-5.19) and for other
      reasons (OR 3.87, CI 1.46-10.25). CONCLUSIONS: The use of herbal medicines during
      pregnancy among women in Gulu district is common, which may be an indicator for
      poor access to conventional western healthcare. Perception that herbal medicines
      are effective and having ever used herbal medicines during previous pregnancy
      were associated with use of herbal medicines during current pregnancy. This
      therefore calls for community sensitization drives on the dangers of
      indiscriminate use of herbal medicine in pregnancy, as well as integration of
      trained traditional herbalists and all those community persons who influence the
      process in addressing the varied health needs of pregnant women.

PMID- 27716106
TI  - In vivo functional and molecular characterization of the Penicillin-Binding
      Protein 4 (DacB) of Pseudomonas aeruginosa.
AB  - BACKGROUND: Community and nosocomial infections by Pseudomonas aeruginosa still
      create a major therapeutic challenge. The resistance of this opportunist pathogen
      to beta-lactam antibiotics is determined mainly by production of the inactivating
      enzyme AmpC, a class C cephalosporinase with a regulation system more complex
      than those found in members of the Enterobacteriaceae family. This regulatory
      system also participates directly in peptidoglycan turnover and recycling. One of
      the regulatory mechanisms for AmpC expression, recently identified in clinical
      isolates, is the inactivation of LMM-PBP4 (Low-Molecular-Mass Penicillin-Binding
      Protein 4), a protein whose catalytic activity on natural substrates has remained
      uncharacterized until now. RESULTS: We carried out in vivo activity trials for
      LMM-PBP4 of Pseudomonas aeruginosa on macromolecular peptidoglycan of Escherichia
      coli and Pseudomonas aeruginosa. The results showed a decrease in the relative
      quantity of dimeric, trimeric and anhydrous units, and a smaller reduction in
      monomer disaccharide pentapeptide (M5) levels, validating the occurrence of D,D
      carboxypeptidase and D,D-endopeptidase activities. Under conditions of induction
      for this protein and cefoxitin treatment, the reduction in M5 is not fully
      efficient, implying that LMM-PBP4 of Pseudomonas aeruginosa presents better
      behaviour as a D,D-endopeptidase. Kinetic evaluation of the direct D,D-peptidase
      activity of this protein on natural muropeptides M5 and D45 confirmed this
      bifunctionality and the greater affinity of LMM-PBP4 for its dimeric substrate. A
      three-dimensional model for the monomeric unit of LMM-PBP4 provided structural
      information which supports its catalytic performance. CONCLUSIONS: LMM-PBP4 of
      Pseudomonas aeruginosa is a bifunctional enzyme presenting both D,D
      carboxypeptidase and D,D-endopeptidase activities; the D,D-endopeptidase function
      is predominant. Our study provides unprecedented functional and structural
      information which supports the proposal of this protein as a potential hydrolase
      autolysin associated with peptidoglycan maturation and recycling. The fact that
      mutant PBP4 induces AmpC, may indicate that a putative muropeptide-subunit
      product of the DD-EPase activity of PBP4 could be a negative regulator of the
      pathway. This data contributes to understanding of the regulatory aspects of
      resistance to beta-lactam antibiotics in this bacterial model.

PMID- 27716107
TI  - "That was intense!" Spirituality during childbirth: a mixed-method comparative
      study of mothers' and fathers' experiences in a public hospital.
AB  - BACKGROUND: While spirituality is well described in end-of-life care literature,
      research on its place in the delivery room remains largely limited to mother
      oriented qualitative studies focusing on life-threatening situations (e.g., high
      risk pregnancies). Our aim was to compare mothers' and fathers' spirituality
      during childbirth. METHODS: A mixed methods questionnaire was developed from our
      childbirth-related spirituality categorization and distributed to all parents of
      newborns, 12-24 h postpartum, over 45 consecutive days. Paired-sample t-tests and
      qualitative thematic analysis were used to compare mothers and fathers. Multiple
      linear regressions identified factors associated with their respective global
      scores (vaginal and cesarean deliveries separately). RESULTS: The global scores
      for mothers (38.6/50) and fathers (37.2/50) were similarly high (N = 197; p =
      0.001). Highest-ranked ("respect", "moral responsibility", "beauty of life",
      "gratitude") and lowest-ranked spiritual themes ("prayer", "greater than self")
      were in agreement. Fathers scored higher on "fragility of life" (p = 0.006) and
      mothers on "self-accomplishment" (p<0.001), "letting go" (p<0.001), and
      "meaningfulness" (p = 0.003). "Admission of baby in neonatal unit" was associated
      with higher global score for both mothers and fathers. Other factors also
      increased fathers' (witnessing a severe tear) and mothers' scores (birthplace
      outside Canada; for vaginal deliveries, religious belonging and longer pushing
      stage). CONCLUSION: These first quantitative data on the prevalence of
      spirituality during childbirth highlight a high score for both parents, among a
      non-selected public hospital population. Spirituality emerges not only from
      unordinary situations but from any childbirth as an "intensification of the human
      experience". Significant differences for some spiritual themes indicate the need
      to consider the spirituality of both parents.

PMID- 27716108
TI  - The therapist's role in the implementation of internet-based cognitive
      behavioural therapy for patients with depression: study protocol.
AB  - BACKGROUND: Internet-based Cognitive Behavioural Therapy (iCBT) for the treatment
      of depressive disorders is innovative and promising. Various studies have
      demonstrated large effect sizes up to 2.27, but implementation in routine
      practice lags behind. Mental health therapists play a significant role in the
      uptake of internet-based interventions. Therefore, it is interesting to study
      factors that influence the therapists in whether they apply internet-based
      therapy or not. This study, as part of the European implementation project
      MasterMind, aims to identity the factors that promote or hinder therapists in the
      use of iCBT in depression care. METHODS/DESIGN: The uptake of iCBT by therapists
      in routine mental health care practice for the treatment of depression will be
      evaluated by a mixed method approach, to provide an understanding of the
      implementation factors (quantitative), and to ascertain the facilitating and
      hindering factors in the involvement of therapists in the implementation of iCBT
      (qualitative). The involvement of therapists in the implementation of iCBT is
      analysed following the RE-AIM framework on the five dimensions Reach,
      Efficacy/Effectiveness, Adoption, Implementation, and Maintenance. This enables
      us to evaluate the reach of therapists, the impact of iCBT on depression care,
      the extent to which therapists adopt iCBT, the extent to which iCBT is delivered
      as intended, and how iCBT can be maintained over time. DISCUSSION: The results
      will provide valuable insight into the role of therapists in the implementation
      of iCBT for depression in secondary mental health care settings. They will result
      in concrete recommendations for how therapists can be facilitated in implementing
      and up-scaling iCBT for depression.

PMID- 27716109
TI  - Erratum to: Sexual behavior of migrant workers in Shanghai, China.

PMID- 27716110
TI  - Metformin in prevention and treatment of antipsychotic induced weight gain: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Most antipsychotics are associated with weight gain and other
      metabolic complications. Several randomized trials have shown metformin to be
      effective, but this still hasn't been included in clinical guidelines on managing
      antipsychotic induced weight gain. METHODS: All double blind placebo controlled
      trials assessing the efficacy of metformin in the treatment of antipsychotic
      induced weight gain were included. Cochrane Central Register of Controlled Trials
      (CENTRAL) and MEDLINE were searched for the period January 2000-December 2015.
      Meta-analysis was carried out using the random effects model. RESULTS: Meta
      analysis of 12 published studies with a total of 743 patients found that in
      patients treated with antipsychotics, metformin treatment resulted in
      significantly better anthropometric and metabolic parameters than placebo. The
      mean change in weight was -3.27 kg (95 % CI -4.66 to -1.89) (Z = 4.64, p <
      0.001). Metformin compared to placebo resulted in significant reduction in BMI [
      1.13 kg/m2 (95 % CI -1.61 to -0.66)] and insulin resistance index [-1.49 (95 % CI
      -2.40 to -0.59)] but not fasting blood sugar [-2.48 mg/dl (95 % CI -5.54 to
      0.57]. CONCLUSION: This meta-analysis confirms that metformin is effective in
      treating antipsychotic induced weight gain in patients with schizophrenia or
      schizoaffective disorder.

PMID- 27716111
TI  - Case report: Aqueous and Vitreous amino-acid concentrations in a patient with
      maple syrup urine disease operated on rhegmatogenous retinal detachment.
AB  - BACKGROUND: Maple syrup urine disease (MSUD) is a rare metabolic disorder,
      affecting the metabolism of branched chain amino-acids (Valine, Leukine,
      Isoleukine). We present a rare case of rhegmatogenous retinal detachment (RRD) in
      a MSUD patient. CASE PRESENTATION: We performed amino acid analysis of aqueous
      humour, vitreous and serum samples obtained during surgery from a 24 year old
      female MSUD patient successfully operated on RRD. Serum values for a-amino
      butyric acid, valine, isoleucine, leucine, tyrosine, phenylalanine, ornithine and
      histidine were low, while values for citrulline, methionine and lysine were
      borderline low, all attributed to the patient's special diet. Serum glutamate was
      above normal, probably due to the breakdown of glutamine to glutamate. In the
      aqueous and vitreous the amino acids implicated in MSUD (Valine, Leukine
      Isoleukine), were within normal range. Glutamate was absent in the vitreous and
      presented low levels in the aqueous. Glutamate has been reported to play an
      important role in retinal damage. Elevated glutamate levels have been reported in
      vitreous specimens from patients subjected to vitrectomy or buckling surgery for
      RRD. In MSUD, glutamate has been implicated in the pathogenesis of brain damage.
      Low levels of glutamate have been observed in the cerebellum of experimental MSUD
      animals, as well as postmortem brain tissue from a child that died of leucine
      intoxication. The reduction was attributed to the elevation of a-ketoisocaproic
      which reverses the net direction of nitrogen flow. It could be argued that this
      could impact on amino acid concentration in aqueous and vitreous fluids.
      CONCLUSIONS: Although no definite conclusions can be drawn by this extremely rare
      case, the low vitreous and aqueous levels of Glutamate is an interesting finding.
      Further studies are needed to provide a better insight in the role of amino acids
      as neurotransmitters in the human eye in health and disease.

PMID- 27716112
TI  - Accommodative changes after SMILE for moderate to high myopia correction.
AB  - BACKGROUND: To investigate accommodative response and accommodative lag changes
      after femtosecond laser small incision lenticule extraction (SMILE) for moderate
      to high myopia correction. METHODS: A total of 32 eyes of 32 patients with no
      strabismus who underwent SMILE were enrolled in this prospective clinical study.
      The accommodative response was obtained viewing monocularly with spherical
      equivalent refractive error corrected, using an open-field autorefractor at
      different stimulus levels (2.00D, 2.50D, 3.00D, 4.00D and 5.00D) for the right
      eye before a standard SMILE surgery and at 1-month follow-up after surgery.
      RESULTS: The mean age of the patients were 23.34 +/- 2.90 years and the mean
      preoperative manifest refraction spherical equivalent was -5.74 +/- 1.98
      diopters. Significant differences were detected in both preoperative and
      postoperative accommodative responses to different stimulus levels (P < 0.001).
      Multiple linear regression model analysis revealed preoperative manifest
      refractive spherical equivalent (P = 0.006) and preoperative accommodative lag (P
      = 0.04) showed a significant impact on postoperative accommodative lag.
      CONCLUSIONS: This is the first report of accommodative changes after SMILE. Our
      preliminary results showed that a decrease in postoperative accommodative lag
      that might be related to the relief of the visual discomfort symptom.

PMID- 27716114
TI  - Histopathology and treatment of a huge overhanging filtering bleb.
AB  - BACKGROUND: The giant filtering bleb encroaching onto the corneal surface is a
      rare occurrence in our and other's clinical experience (Kapoor and Syed, Int.
      Ophthalmol 31(5):403-404, 2011), even in patients having had a trabeculectomy
      with mitomycin C, and how it developed is debated. In this paper, we report a
      patient who developed a huge overhanging filtering bleb after trabeculectomy, and
      present our intraoperative photographs, histopathology and immunohistochemistry
      results. CASE PRESENTATION: A 62-year-old female visited our hospital due to the
      giant filtering bleb encroaching onto the corneal surface which was about 6 mm *
      8 mm * 3 mm. We dissected the filtering bleb from the cornea and present the
      histopathology and immunohistochemistry results of it. CONCLUSION: The results
      from histopathology and immunohistochemistry in this study are consistent with
      the filtering cicatrix hypothesis. However, our finding that the overhanging
      blebs had tight connections with the corneal tissue or corneoscleral limbus,
      rather than simply leaning on it, might be highly related to their development
      and still needs to be further studied.

PMID- 27716113
TI  - Predictive factors of dropout from inpatient treatment for anorexia nervosa.
AB  - BACKGROUND: Patients with severe Anorexia Nervosa (AN) whose condition is life
      threatening or who are not receiving adequate ambulatory care are hospitalized.
      However, 40 % of these patients leave the hospital prematurely, without reaching
      the target weight set in the treatment plan, and this can compromise outcome.
      This study set out to explore factors predictive of dropout from hospital
      treatment among patients with AN, in the hope of identifying relevant therapeutic
      targets. METHODS: From 2009 to 2011, 180 women hospitalized for AN (DSM-IV
      diagnosis) in 10 centres across France were divided into two groups: those under
      18 years (when the decision to discharge belongs to the parents) and those aged
      18 years and over (when the patient can legally decide to leave the hospital).
      Both groups underwent clinical assessment using the Morgan & Russell Global
      Outcome State questionnaire and the Eating Disorders Examination Questionnaire
      (EDE-Q) for assessment of eating disorder symptoms and outcome. Psychological
      aspects were assessed via the evaluation of anxiety and depression using the
      Hospital Anxiety and Depression Scale (HADS). Socio-demographic data were also
      collected. A number of factors identified in previous research as predictive of
      dropout from hospital treatment were tested using stepwise descending Cox
      regressions. RESULTS: We found that factors predictive of dropout varied
      according to age groups (being under 18 as opposed to 18 and over). For
      participants under 18, predictive factors were living in a single-parent family,
      severe intake restriction as measured on the "dietary restriction" subscale of
      the Morgan & Russell scale, and a low patient-reported score on the EDE-Q
      "restraint concerns" subscale. For those over 18, dropout was predicted from a
      low depression score on the HADS, low level of concern about weight on the EDE-Q
      subscale, and lower educational status. CONCLUSION: To prevent dropout from
      hospitalization for AN, the appropriate therapeutic measures vary according to
      whether patients are under or over 18 years of age. Besides the therapeutic
      adjustments required in view of the factors identified, the high dropout rate
      raises the issue of resorting more frequently to compulsory care measures among
      adults.

PMID- 27716115
TI  - Relationship between negative symptoms and neurocognitive functions in adolescent
      and adult patients with first-episode schizophrenia.
AB  - BACKGROUND: This study aimed to explore differences in links between negative
      symptoms and neurocognitive deficits in adolescent and adult patients with first
      episode schizophrenia. Schizophrenia is a mental disorder often characterized by
      positive and negative symptoms, reduced emotional expression, excitatory status,
      and poor cognitive ability. The severity of negative symptoms in patients with
      schizophrenia was reported to be more related to poor quality of life, weak
      functional ability, and heavy burden from families than with the severity of
      positive symptoms. Previous studies suggested correlations between the severity
      of negative symptoms in patients with schizophrenia and neurocognitive deficits.
      METHODS: This study included 92 patients (33 adolescents and 59 adults) with
      first-episode schizophrenia and 57 healthy people matched by age and education
      level. Neurocognitive functions and clinical symptoms were assessed using a
      standardized questionnaire. RESULTS: Patients with first-episode schizophrenia
      showed neurocognitive deficits in most neuropsychological assessments compared
      with healthy people. With the variable of education level controlled, the
      negative factor score of adolescent patients with first-episode schizophrenia was
      strongly correlated with more time spent in part 1 (r = .646) and part 2 (r =
      .663) of the trail making test, and moderately correlated to more perseverative
      errors (r = .425) of the Wisconsin card sorting test and fewer correct trials 2
      (r = -.425) of the continuous performance test. However, no such correlations
      were found in adult patients. CONCLUSIONS: This study indicated significant
      correlations between negative symptoms and most neurocognitive functions in
      patients with first-episode schizophrenia, with a stronger correlation in
      adolescent patients. TRIAL REGISTRATION: The trial registration number is ChiCTR
      COC-14005302 , while retrospectively registered on January 5, 2014.

PMID- 27716116
TI  - Data in longitudinal randomised controlled trials in cancer pain: is there any
      loss of the information available in the data? Results of a systematic literature
      review and guideline for reporting.
AB  - BACKGROUND: Given the prevalence of untreated pain among cancer patients, there
      have been calls for more and better research in the domain. Increasingly, calls
      for less waste and more optimal use of trial data collected are being made. Waste
      of data includes non-optimal statistical analysis and non-presentation of
      interpretable effect size as a measure of effectiveness of an intervention which
      also enable comparisons across studies. METHODS: We reviewed the recent
      literature on randomised trials on longitudinal cancer pain to identify sources
      of loss of data information by collecting material on the nature of outcomes
      collected, analysed, the method of analysis and what was presented as a result of
      the trial. Illustrated with real data, we propose some guidelines on how to
      adequately analyse longitudinal data and report the results using mixed models.
      RESULTS: We identified some major source of data information loss, one of which
      is the transformation of a continuous pain outcome. Not adjusting for the
      collected outcome baseline value is moreover a source of bias. Multiple testing
      by analysing the data cross-sectionnally at each time-point leads to loss of
      information and power. Finally, effect sizes reflecting the effectiveness of the
      intervention were never reported. CONCLUSIONS: We identified several sources of
      information loss in the way longitudinal trials on pain were analysed and
      reported. However these problems could be easily solved by using regression
      methods like mixed models and presenting regression parameters to provide a
      concrete quantitative effect of the intervention.

PMID- 27716117
TI  - The experience of Greek-Cypriot individuals living with mental illness:
      preliminary results of a phenomenological study.
AB  - BACKGROUND: Research evidence shows that healthcare professionals do not fully
      comprehend the difficulty involved in problems faced by people living with severe
      mental illness (SMI). As a result, mental health service consumers do not show
      confidence in the healthcare system and healthcare professionals, a problem
      related to the phenomenon of adherence to therapy. Moreover, the issue of unmet
      needs in treating individuals living with SMI is relared to their quality of life
      in a negative way. METHODS: A qualitative methodological approach based on the
      methodology of van Manen phenomenology was employed through a purposive sampling
      of ten people living with SMI. The aim was to explore their perceptions and
      interpretations regarding: a) their illness, b) their self-image throughout the
      illness, c) the social implications following their illness, and d) the quality
      of the therapeutic relationship with mental health nurses. Participants were
      recruited from a community mental health service in a Greek-Cypriot urban city.
      Data were collected through personal, semi-structured interviews. RESULTS:
      Several main themes were identified through the narratives of all ten
      participants. Main themes included: a) The meaning of mental illness, b) The
      different phases of the illness in time, c) The perception of the self during the
      illness, d) Perceptions about the effectiveness of pharmacotherapy, e) Social and
      personal consequences for participants following the diagnosis of mental illness,
      f) Participants' perceptions regarding mental health professionals and services
      and g) The therapeutic effect of the research interview on the participants.
      CONCLUSIONS: The present study provides data for the enhancement of the empathic
      understanding of healthcare professionals regarding the concerns and particular
      needs of individuals living with SMI, as well as the formation of targeted
      psychosocial interventions based on these needs. Overall, the present data
      illuminate the necessity for the reconstruction of the provided mental healthcare
      in Cyprus into a more recovery- oriented approach in order to address personal
      identity and self-determination issues and the way these are related to
      management of pharmacotherapy. Qualitative studies aiming to further explore
      issues of self-identity during ill health and its association with adherence to
      therapy, resilience and self-determination, are also proposed.

PMID- 27716120
TI  - Erratum to: 'Pre-endoscopy point of care test (Simtomax- IgA/IgG-Deamidated
      Gliadin Peptide) for coeliac disease in iron deficiency anaemia: diagnostic
      accuracy and a cost saving economic model'.

PMID- 27716119
TI  - A survey of physician receptivity to molecular diagnostic testing and readiness
      to act on results for early-stage colon cancer patients.
AB  - BACKGROUND: We sought to assess physician interest in molecular prognosic testing
      for patients with early stage colon cancer, and identify factors associated with
      the likelihood of test adoption. METHODS: We identified physicians who care for
      patients with early-stage (pN0) colon cancer patients, mailed them a survey, and
      analyzed survey responses to assess clinician receptivity to the use of a new
      molecular test (GUCY2C) that identifies patients at risk for recurrence, and
      clinician readiness to act on abnormal test results. RESULTS: Of 104 eligible
      potential respondents, 41 completed and returned the survey. Among responding
      physicians, 56 % were receptive to using the new prognostic test. Multivariable
      analyses showed that physicians in academic medical centers were significantly
      more receptive to molecular test use than those in non-academic settings. Forty
      one percent of respondents were ready to act on abnormal molecular test results.
      Physicians who viewed current staging methods as inaccurate and were confident in
      their capacity to incorporate molecular testing in practice were more likely to
      say they would act on abnormal test results. CONCLUSIONS: Physician receptivity
      to molecular diagnostic testing for early-stage colon cancer patients is likely
      to be influenced by practice setting and perceptions related to delivering
      quality care to patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01972737.

PMID- 27716118
TI  - Selective depletion of tumour suppressors Deleted in Colorectal Cancer (DCC) and
      neogenin by environmental and endogenous serine proteases: linking diet and
      cancer.
AB  - BACKGROUND: The related tumour suppressor proteins Deleted in Colorectal Cancer
      (DCC) and neogenin are absent or weakly expressed in many cancers, whereas their
      insertion into cells suppresses oncogenic behaviour. Serine proteases influence
      the initiation and progression of cancers although the mechanisms are unknown.
      METHODS: The effects of environmental (bacterial subtilisin) and endogenous
      mammalian (chymotrypsin) serine proteases were examined on protein expression in
      fresh, normal tissue and human neuroblastoma and mammary adenocarcinoma lines.
      Cell proliferation and migration assays (chemoattraction and wound closure) were
      used to examine cell function. Cells lacking DCC were transfected with an ectopic
      dcc plasmid. RESULTS: Subtilisin and chymotrypsin selectively depleted DCC and
      neogenin from cells at nanomolar concentrations without affecting related
      proteins. Cells showed reduced adherence and increased migration, but after
      washing they re-attached within 24 h, with recovery of protein expression. These
      effects are induced by chymotryptic activity as they are prevented by chymostatin
      and the soybean Bowman-Birk inhibitor typical of many plant protease inhibitors.
      CONCLUSIONS: Bacillus subtilis, which secretes subtilisin is widely present in
      soil, the environment and the intestinal contents, while subtilisin itself is
      used in meat processing, animal feed probiotics and many household cleaning
      agents. With chymotrypsin present in chyme, blood and tissues, these proteases
      may contribute to cancer development by depleting DCC and neogenin. Blocking
      their activity by Bowman-Birk inhibitors may explain the protective effects of a
      plant diet. Our findings identify a potential non-genetic contribution to cancer
      cell behaviour which may explain both the association of processed meats and
      other factors with cancer incidence and the protection afforded by plant-rich
      diets, with significant implications for cancer prevention.

PMID- 27716122
TI  - Atypical presentation of primary intraocular lymphoma.
AB  - BACKGROUND: In 2014, Pang et al. reported three cases with vitelliform
      submaculopathy as a preceding lesion of primary intraocular lymphoma (PIOL).
      Here, we report a case with an atypical presentation of PIOL who initially
      presented with vitelliform submaculopathy, vitreous haze and preripheral retinal
      focus. CASE PRESENTATION: A 73-year-old female initially visited another hospital
      with a chief complaint of acute reduced vision in the right eye. Funduscopic
      examination of the right eye showed a yellowish retinal lesion at the fovea with
      vitreous haze and retinal foci scattered in the peripheral region. Spectral
      domain optic coherence tomography (SD-OCT) revealed a hyperreflective subretinal
      debris above the retinal pigment epithelium (RPE) at the fovea, suggesting
      vitelliform submaculopathy. Vitrectomy was performed to improve visualization of
      the retinal lesions and for examination of PIOL. Vitreous cytology was class III
      and cytokine analysis of vitreous fluid showed increased IL-10 and an IL-10/IL-6
      ratio >1, suggesting PIOL. Thereafter, there was a sub-RPE infiltration of
      presumed lymphoma in the nasal retina, and PCR analysis of anterior chamber fluid
      indicated IgH gene rearrangement, leading to diagnosis of PIOL. Three months
      later, there was complete disappearance of the vitelliform submacular lesion,
      with resultant disruption and thinning of the outer retinal layers on SD-OCT
      images. CONCLUSIONS: Clinicians should be aware of atypical manifestations of
      PIOL such as vitelliform submaculopathy and peripheral retinal foci with vitreous
      haze. The patient's unusual funduscopic changes are findings that have not
      reported in patients with PIOL.

PMID- 27716123
TI  - Effectiveness of bandage contact lens application in corneal epithelialization
      and pain alleviation following corneal transplantation; prospective, randomized
      clinical trial.
AB  - BACKGROUND: To assess the efficacy of bandage contact lens (BCL) application to
      promote epithelialization and alleviate pain following corneal transplantation.
      METHODS: Twenty-six consecutive patients who underwent corneal transplantation
      were randomly assigned to undergo BCL application (BCL group, n = 14) or no BCL
      application (control group, n = 12) at the end of the surgery. Corneal
      epithelialization was analyzed by photography using fluorescein staining, and
      ocular pain was measured using a visual analog scale. RESULTS: The mean size of
      the epithelial defect relative to the graft area in the BCL group was 21.80 +/-
      35.10 % at the end of surgery, 18.20 +/- 31.10 % on postoperative day 1, and 5.45
      +/- 11.10 % on postoperative days 3 to 5. These values in the control group were
      9.64 +/- 17.60 % at the end of surgery, 11.50 +/- 25.70 % on postoperative day 1,
      and 0.00 +/- 0.00 % on postoperative days 3 to 5. There were no significant
      differences in the speed of epithelialization between the two groups. The mean
      preoperative pain score in the BCL group was slightly higher than that control
      (4.27 +/- 1.96 vs. 2.41 +/- 2.18, respectively; P = 0.039). The scores
      significantly increased on postoperative day 1 and promptly returned to
      preoperative levels by day 7 in both groups, and there were no significant
      differences between the groups. CONCLUSIONS: No significant benefits of BCL
      application at the time of corneal transplantation were observed in this study.
      The efficacy and safety of BCLs in eyes with compromised epithelialization
      require further study. TRIAL REGISTRATION NUMBER: UMIN 000019091 . Date of
      registration: 2015/09/22.

PMID- 27716121
TI  - Leucine-rich diet alters the 1H-NMR based metabolomic profile without changing
      the Walker-256 tumour mass in rats.
AB  - BACKGROUND: Cachexia is one of the most important causes of cancer-related death.
      Supplementation with branched-chain amino acids, particularly leucine, has been
      used to minimise loss of muscle tissue, although few studies have examined the
      effect of this type of nutritional supplementation on the metabolism of the
      tumour-bearing host. Therefore, the present study evaluated whether a leucine
      rich diet affects metabolomic derangements in serum and tumour tissues in tumour
      bearing Walker-256 rats (providing an experimental model of cachexia). METHODS:
      After 21 days feeding Wistar female rats a leucine-rich diet, distributed in L
      leucine and LW-leucine Walker-256 tumour-bearing groups, we examined the
      metabolomic profile of serum and tumour tissue samples and compared them with
      samples from tumour-bearing rats fed a normal protein diet (C - control; W -
      tumour-bearing groups). We utilised 1H-NMR as a means to study the serum and
      tumour metabolomic profile, tumour proliferation and tumour protein synthesis
      pathway. RESULTS: Among the 58 serum metabolites examined, we found that 12 were
      altered in the tumour-bearing group, reflecting an increase in activity of some
      metabolic pathways related to energy production, which diverted many nutrients
      toward tumour growth. Despite displaying increased tumour cell activity (i.e.,
      higher Ki-67 and mTOR expression), there were no differences in tumour mass
      associated with changes in 23 metabolites (resulting from valine, leucine and
      isoleucine synthesis and degradation, and from the synthesis and degradation of
      ketone bodies) in the leucine-tumour group. This result suggests that the
      majority of nutrients were used for host maintenance. CONCLUSION: A leucine rich
      diet, largely used to prevent skeletal muscle loss, did not affect Walker 256
      tumour growth and led to metabolomic alterations that may partially explain the
      positive effects of leucine for the whole tumour-bearing host.

PMID- 27716124
TI  - Safer drug use in primary care - a pilot intervention study to identify
      improvement needs and make agreements for change in five Swedish primary care
      units.
AB  - BACKGROUND: There is an urgent need to improve patient safety in the area of
      medication treatment among the elderly. The aim of this study was to explore
      which improvement needs and strengths, relating to medication safety, arise from
      a multi-professional intervention in primary care and further to describe and
      follow up on the agreements for change that were established within the
      intervention. METHODS: The SAKLAK project was a multi-professional intervention
      in primary care consisting of self-assessment, peer-review, feedback and written
      agreements for change. Data were obtained from five primary care units randomised
      to the intervention group. Reviewer feedback reports and agreements for change
      were analysed using content analysis. RESULTS: Strengths that were identified
      included a committed leadership, work methods to enhance medication safety and
      access to consultants. Methods for securing an accurate medication list,
      knowledge and methods of working of the prescriber and patient's ability to
      contribute to medication safety were areas that gave rise to three predesigned
      categories for improvement needs on a local level. Another category became
      apparent during the analysis; namely learning from mistakes and from results. In
      all categories, apparent shortcomings were identified. These included inaccurate
      medication lists, lack of medication reconciliation, lack of time for follow-up
      of elderly patients, need for further education in geriatrics and pharmacotherapy
      and lack of information on indication and maximum dosage. An increased number of
      medication reviews were among the most common agreements for change seen.
      CONCLUSIONS: This study identified substantial shortcomings, like poorly updated
      medication lists, which affected medication safety in the participating Swedish
      primary care units. Similar shortcomings are most likely present in other primary
      care units in the country. Working together multi-professionally, including
      performing medication reviews, could be one way of improving medication safety.
      On the other hand, the individual physician must possess enough pharmaceutical
      knowledge and the working conditions must allow time for follow-up of
      prescriptions. Strengths of the primary care unit, such as successful methods of
      working, must be taken advantage of. The culture in primary care may affect the
      ability to successfully implement routines that improve patient safety and reduce
      risk of medication errors.

PMID- 27716126
TI  - Unraveling the molecular basis of oxidative stress management in a drought
      tolerant rice genotype Nagina 22.
AB  - BACKGROUND: Drought stress tolerance for crop improvement is an important goal
      worldwide. Drought is a complex trait, and it is vital to understand the complex
      physiological, biochemical, and molecular mechanisms of drought tolerance to 
      tackle  it effectively. Osmotic adjustment, oxidative stress management (OSM),
      and cell membrane stability (CMS) are major components of cellular tolerance
      under drought stress. In the current study, we explored the molecular basis of
      OSM in the drought tolerant rice variety, Nagina 22 and compared it with the
      popular drought sensitive rice variety, IR 64, under drought imposed at the
      reproductive stage, to understand how the parental polymorphisms correlate with
      the superiority of Nagina 22 and tolerant bulk populations under drought.
      RESULTS: We generated recombinant inbred lines (RIL) from contrasting parents
      Nagina 22 and IR 64 and focussed on spikelet fertility (SF), in terms of its
      correlation with OSM, which is an important component of drought tolerance in
      Nagina 22. Based on SF under drought stress and its correlations with other yield
      related traits, we used superoxide dismutase (SOD), glutathione reductase (GR),
      and ascorbate peroxidase (APX) activity assays to establish the relationship
      between SF and OSM genes in the tolerant and sensitive lines. Among the OSM
      enzymes studied, GR had a significant and positive correlation with single plant
      yield (SPY) under drought stress. GR was also positively correlated with APX but
      negatively so with SOD. Interestingly, none of the enzyme-morphology correlations
      were significant under irrigated control (IC). Through genome-wide SNP analysis
      of the 21 genes encoding for OSM enzymes, we identified the functional
      polymorphisms between the parents and identified superior alleles. By using
      network analysis of OSM genes in rice, we identified the genes that are central
      to the OSM network. CONCLUSIONS: From the biochemical and morphological data and
      the SNP analysis, the superiority of Nagina 22 in spikelet fertility under
      drought stress is because of its superior alleles for SOD (SOD2, SODCC1, SODA)
      and GR (GRCP2) rather than for APX, for which IR 64 had the superior allele
      (APX8). Nagina 22 can bypass APX8 by directly interacting with SODA. For nine of
      the 11 genes present in the central network, Nagina 22 had the superior alleles.
      We propose that Nagina 22 tolerance could mainly be because of SODA which is a
      reactive oxygen scavenger in mitochondria which is directly associated with
      spikelet fertility.

PMID- 27716127
TI  - Level of nutrition knowledge and its association with fat consumption among
      college students.
AB  - BACKGROUND: Intake of saturated fat, trans fat, and cholesterol has been
      associated with increased risk of coronary heart disease. The aim of this study
      was to explore whether increased nutrition knowledge is associated with a
      reduction in the consumption of unhealthy fats in a sample of university
      students. METHODS: A sample of 231 students, with a mean age of 20 years, was
      recruited from university campus during spring 2012. Students completed a
      validated questionnaire related to students' demographic, nutrition knowledge,
      and daily fat consumption. Weight, height, and waist circumference were measured.
      Data were analyzed using one-way ANOVA, chi-square, and student's t-test.
      RESULTS: Results indicate that female students have greater nutrition knowledge
      than male students (the mean nutrition score for women was 5 points higher than
      that of men (P = 0.01)). Nutrition knowledge was negatively correlated with fat
      and cholesterol intake. Students who consumed more than 35 % calories from fat or
      >300 mg of cholesterol daily had lower mean nutrition scores than those students
      with lower fat or cholesterol intake (8 points lower and 7.9 points lower,
      respectively). Using linear regression for nutrition scores on estimated
      saturated fat intake and cholesterol intake (controlling for gender, height,
      weight, age, and dieting), nutrition scores were negatively associated with
      saturated fat intake (-0.15, P <0.0001) and cholesterol intake (-1.38, P
      <0.0001). CONCLUSION: Students with greater nutritional knowledge consumed less
      unhealthy fats and cholesterol. This finding magnifies the role of nutrition
      education as a potential tool in health campaigns to promote healthy eating
      patterns among college students. Results of this pilot study can inform the
      design of future nutrition education intervention studies to assess the efficacy
      of nutrition knowledge on pattern of fat consumption among college students.

PMID- 27716125
TI  - DARS: a phase III randomised multicentre study of dysphagia- optimised intensity-
      modulated radiotherapy (Do-IMRT) versus standard intensity- modulated
      radiotherapy (S-IMRT) in head and neck cancer.
AB  - BACKGROUND: Persistent dysphagia following primary chemoradiation (CRT) for head
      and neck cancers can have a devastating impact on patients' quality of life.
      Single arm studies have shown that the dosimetric sparing of critical swallowing
      structures such as the pharyngeal constrictor muscle and supraglottic larynx can
      translate to better functional outcomes. However, there are no current randomised
      studies to confirm the benefits of such swallow sparing strategies. The aim of
      Dysphagia/Aspiration at risk structures (DARS) trial is to determine whether
      reducing the dose to the pharyngeal constrictors with dysphagia-optimised
      intensity- modulated radiotherapy (Do-IMRT) will lead to an improvement in long-
      term swallowing function without having any detrimental impact on disease
      specific survival outcomes. METHODS/DESIGN: The DARS trial (CRUK/14/014) is a
      phase III multicentre randomised controlled trial (RCT) for patients undergoing
      primary (chemo) radiotherapy for T1-4, N0-3, M0 pharyngeal cancers. Patients will
      be randomised (1:1 ratio) to either standard IMRT (S-IMRT) or Do-IMRT.
      Radiotherapy doses will be the same in both groups; however in patients allocated
      to Do-IMRT, irradiation of the pharyngeal musculature will be reduced by
      delivering IMRT identifying the pharyngeal muscles as organs at risk. The primary
      endpoint of the trial is the difference in the mean MD Anderson Dysphagia
      Inventory (MDADI) composite score, a patient-reported outcome, measured at 12
      months post radiotherapy. Secondary endpoints include prospective and
      longitudinal evaluation of swallow outcomes incorporating a range of subjective
      and objective assessments, quality of life measures, loco-regional control and
      overall survival. Patients and speech and language therapists (SLTs) will both be
      blinded to treatment allocation arm to minimise outcome-reporting bias.
      DISCUSSION: DARS is the first RCT investigating the effect of swallow sparing
      strategies on improving long-term swallowing outcomes in pharyngeal cancers. An
      integral part of the study is the multidimensional approach to swallowing
      assessment, providing robust data for the standardisation of future swallow
      outcome measures. A translational sub- study, which may lead to the development
      of future predictive and prognostic biomarkers, is also planned. TRIAL
      REGISTRATION: This study is registered with the International Standard Randomised
      Controlled Trial register, ISRCTN25458988 (04/01/2016).

PMID- 27716128
TI  - Is tailored treatment superior to non-tailored treatment for pain and disability
      in women with non-specific neck pain? A randomized controlled trial.
AB  - BACKGROUND: The evidence for the effect of treatments of neck pain is modest. In
      the absence of causal treatments, a possibility is to tailor the treatment to the
      individuals' functional limitations and symptoms. The aim was to evaluate
      treatment effects of a tailored treatment versus a non-tailored treatment. Our
      hypothesis was that tailored treatment (TT) would have better effect on pain
      intensity and disability than either non-tailored treatment (NTT) (same treatment
      components but applied quasi-randomly) or treatment-as-usual (TAU) (no treatment
      from the study, no restrictions). We further hypothesized that TT and NTT would
      both have better effect than TAU. METHOD: One hundred twenty working women with
      subacute and chronic non-specific neck pain were allocated to 11 weeks of either
      TT, NTT or TAU in a randomized controlled trial with follow-ups at 3, 9 and 15
      months. The TT was designed from a decision model based on assessment of function
      and symptoms with defined cut-off levels for the following categories: reduced
      cervical mobility, impaired neck-shoulder strength and motor control, impaired
      eye-head-neck control, trapezius myalgia and cervicogenic headache. Primary
      outcomes were pain and disability. Secondary outcomes were symptoms, general
      improvement, work productivity, and pressure pain threshold of m. trapezius.
      RESULTS: Linear mixed models analysis showed no differences between TT and NTT
      besides work productivity favoring TT at 9- and 15-months follow-ups. TT and NTT
      improved significantly more than TAU on pain, disability and symptoms at 3-month
      follow-up. General improvement also favored TT and NTT over TAU at all follow
      ups. CONCLUSION: Tailored treatment according to our proposed decision model was
      not more effective than non-tailored treatment in women with subacute and chronic
      neck pain. Both tailored and non-tailored treatments had better short-term
      effects than treatment-as-usual, supporting active and specific exercise therapy,
      although therapist-patient interaction was not controlled for. Better
      understanding of the importance of functional impairments for pain and
      disability, in combination with a more precise tailoring of specific treatment
      components, is needed to progress. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN 49348025. Registered 2 August 2011.

PMID- 27716129
TI  - Predictors of homelessness among vulnerably housed adults in 3 Canadian cities: a
      prospective cohort study.
AB  - BACKGROUND: Homelessness is a major concern in many urban communities across
      North America. Since vulnerably housed individuals are at risk of experiencing
      homelessness, it is important to identify predictive factors linked to subsequent
      homelessness in this population. The objectives of this study were to determine
      the probability of experiencing homelessness among vulnerably housed adults over
      three years and factors associated with higher risk of homelessness. METHODS:
      Vulnerably housed adults were recruited in three Canadian cities. Data on
      demographic characteristics, chronic health conditions, and drug use problems
      were collected through structured interviews. Housing history was obtained at
      baseline and annual follow-up interviews. Generalized estimating equations were
      used to characterize associations between candidate predictors and subsequent
      experiences of homelessness during each follow-up year. RESULTS: Among 561
      participants, the prevalence of homelessness was 29.2 % over three years. Male
      gender (AOR = 1.59, 95 % CI: 1.14-2.21) and severe drug use problems (AOR = 1.98,
      95 % CI: 1.22-3.20) were independently associated with experiencing homelessness
      during the follow-up period. Having >=3 chronic conditions (AOR = 0.55, 95 % CI:
      0.33-0.94) and reporting higher housing quality (AOR = 0.99, 95 % CI: 0.97-1.00)
      were protective against homelessness. CONCLUSIONS: Vulnerably housed individuals
      are at high risk for experiencing homelessness. The study has public health
      implications, highlighting the need for enhanced access to addiction treatment
      and improved housing quality for this population.

PMID- 27716130
TI  - Novel microRNA discovery using small RNA sequencing in post-mortem human brain.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene
      expression mainly through translational repression of target mRNA molecules. More
      than 2700 human miRNAs have been identified and some are known to be associated
      with disease phenotypes and to display tissue-specific patterns of expression.
      METHODS: We used high-throughput small RNA sequencing to discover novel miRNAs in
      93 human post-mortem prefrontal cortex samples from individuals with Huntington's
      disease (n = 28) or Parkinson's disease (n = 29) and controls without
      neurological impairment (n = 36). A custom miRNA identification analysis pipeline
      was built, which utilizes miRDeep* miRNA identification and result filtering
      based on false positive rate estimates. RESULTS: Ninety-nine novel miRNA
      candidates with a false positive rate of less than 5 % were identified. Thirty
      four of the candidate miRNAs show sequence similarity with known mature miRNA
      sequences and may be novel members of known miRNA families, while the remaining
      65 may constitute previously undiscovered families of miRNAs. Nineteen of the 99
      candidate miRNAs were replicated using independent, publicly-available human
      brain RNA-sequencing samples, and seven were experimentally validated using qPCR.
      CONCLUSIONS: We have used small RNA sequencing to identify 99 putative novel
      miRNAs that are present in human brain samples.

PMID- 27716132
TI  - The effect of financial incentives on top of behavioral support on quit rates in
      tobacco smoking employees: study protocol of a cluster-randomized trial.
AB  - BACKGROUND: Stimulating successful tobacco cessation among employees has multiple
      benefits. Employees who quit tobacco are healthier, more productive, less absent
      from work, and longer employable than employees who continue to use tobacco.
      Despite the evidence for these benefits of tobacco cessation, a successful method
      to stimulate employees to quit tobacco is lacking. The aim of this study is to
      evaluate whether adding a financial incentive to behavioral support (compared
      with no additional incentive) is effective and cost-effective in increasing
      abstinence rates in tobacco smoking employees participating in a smoking
      cessation group training. METHODS/DESIGN: In this cluster-randomized trial
      employees in the intervention and control group both participate in a smoking
      cessation group training consisting of seven weekly counseling sessions of ninety
      minutes each. In addition to the training, employees in the intervention group
      receive a voucher as an incentive for being abstinent from smoking at the end of
      the training (?50), after three months (?50), after six months (?50), and after
      one year (?200). The control group does not receive any incentive. The primary
      outcome is carbon monoxide validated 12-month continuous abstinence from smoking
      (Russel's standard). Additionally, an economic evaluation is performed from a
      societal and an employer perspective. DISCUSSION: The present paper describes the
      methods and design of this cluster-randomized trial in detail. We hypothesize
      that the financial incentive for abstinence in the form of vouchers increases
      abstinence rates over and above the group training. The results of this study can
      provide important recommendations for enhancement of employee tobacco cessation.
      TRIAL REGISTRATION: Dutch Trial Register: NTR5657 . First received 27-01-2016.

PMID- 27716131
TI  - Rationale and Design of the CREDENCE Trial: computed TomogRaphic evaluation of
      atherosclerotic DEtermiNants of myocardial IsChEmia.
AB  - BACKGROUND: Coronary computed tomography angiography (CCTA) allows for non
      invasive assessment of obstructive coronary artery disease (CAD) beyond measures
      of stenosis severity alone. This assessment includes atherosclerotic plaque
      characteristics (APCs) and calculation of fractional flow reserve (FFR) from CCTA
      (FFRCT). Similarly, stress imaging by myocardial perfusion scintigraphy (MPS)
      provides vital information. To date, the diagnostic performance of integrated
      CCTA assessment versus integrated MPS assessment for diagnosis of vessel-specific
      ischemia remains underexplored. METHODS: CREDENCE will enroll adult individuals
      with symptoms suspicious of CAD referred for non-emergent invasive coronary
      angiography (ICA), but without known CAD. All participants will undergo CCTA,
      MPS, ICA and FFR. FFR will be performed for lesions identified at the time of ICA
      to be >=40 and <90 % stenosis, or those clinically indicated for evaluation.
      Study analyses will focus on diagnostic performance of CCTA versus MPS against
      invasive FFR reference standard. An integrated stenosis-APC-FFRCT metric by CCTA
      for vessel-specific ischemia will be developed from derivation cohort and tested
      against a validation cohort. Similarly, integrated metric by MPS for vessel
      specific ischemia will be developed, validated and compared. An FFR value of
      <=0.80 will be considered as ischemia causing. The primary endpoint will be the
      diagnostic accuracy of vessel territory-specific ischemia of integrated stenosis
      APC-FFRCT measure by CCTA, compared with perfusion or perfusion-myocardial blood
      flow stress imaging testing, against invasive FFR. DISCUSSION: CREDENCE will
      determine the performance of integrated CCTA metric compared to integrated MPS
      measure for diagnosis of vessel-specific ischemia. If proven successful, this
      study may reduce the number of missed diagnoses and help to optimally predict
      ischemia-causing lesions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02173275 .
      Registered on June 23, 2014.

PMID- 27716134
TI  - Erratum to: A systematic review of the health and well-being impacts of school
      gardening: synthesis of quantitative and qualitative evidence.

PMID- 27716133
TI  - Diet quality is associated with obesity and hypertension in Australian adults: a
      cross sectional study.
AB  - BACKGROUND: Poor diet, characterized by a low diet quality score, has been
      associated with greater prevelence of obesity and hypertension. However, the
      evidence is inconsistent across diet quality scores and by sex. The aim was to
      investigate the relationship between diet quality and obesity and hypertension.
      METHODS: Adults (n = 4908; age 45.2 +/- 0.24 years) were included from the cross
      sectional Australian Health Survey 2011-2013. Two 24-h dietary recalls were used
      to derive the dietary guideline index (DGI) and recommended food score (RFS).
      Logistic regression investigated relationships between diet quality score and
      odds ratio of obesity, hypertension and obesity-associated hypertension. RESULTS:
      In the highest tertile of DGI, but not RFS, individuals were less likely to be
      obese (men: OR 0.64, CI: 0.45, 0.92, P-trend = 0.014; women: 0.68, 0.48, 0.96, P
      trend = 0.025) and to have central adiposity (men: 0.68, 0.48, 0.97, P-trend =
      0.030; women: 0.53, 0.37, 0.77, P-trend = 0.001) compared with the lowest
      tertile. Men, but not women, in the highest tertile of DGI and RFS were less
      likely to be hypertensive (DGI: 0.56, 0.37, 0.85, P-trend = 0.006; RFS: 0.62,
      0.41, 0.94, P-trend = 0.021) compared with the lowest tertile. In men with
      obesity, but not normal weight men or women, those in the highest tertile of DGI
      were less likely to be hypertensive (0.53, 0.36, 0.78, P-trend = 0.001) compared
      with the highest tertile. CONCLUSIONS: Higher diet quality, as estimated using
      DGI, was associated with lower odds ratio of obesity in men and women. Odds ratio
      of hypertension was lower in men, but not women, with a high diet quality score
      compared with a low score, while obesity-associated hypertension was only
      associated with diet quality score in men with obesity. Longitudinal studies are
      needed to evaluate whether diet quality predicts risk of obesity and
      hypertension.

PMID- 27716135
TI  - Remaining missed opportunities of child survival in Peru: modelling mortality
      impact of universal and equitable coverage of proven interventions.
AB  - BACKGROUND: Peru has made great improvements in reducing stunting and child
      mortality in the past decade, and has reached the Millennium Development Goals 1
      and 4. The remaining challenges or missed opportunities for child survival needs
      to be identified and quantified, in order to guide the next steps to further
      improve child survival in Peru. METHODS: We used the Lives Saved Tool (LiST) to
      project the mortality impact of proven interventions reaching every women and
      child in need, and the mortality impact of eliminating inequalities in coverage
      distribution between wealth quintiles and urban-rural residence. RESULTS: Our
      analyses quantified the remaining missed opportunities in Peru, where
      prioritizing scale-up of facility-based case management for all small and sick
      babies will be most effective in mortality reduction, compared to other evidenced
      based interventions that prevent maternal and child deaths. Eliminating coverage
      disparities between the poorest quintiles and the richest will reduce under-five
      and neonatal mortality by 22.0 and 40.6 %, while eliminating coverage disparities
      between those living in rural and urban areas will reduce under-five and neonatal
      mortality by 29.3 and 45.2 %. This projected neonatal mortality reduction
      achieved by eliminating coverage disparities is almost comparable to that already
      achieved by Peru over the past decade. CONCLUSIONS: Although Peru has made great
      strides in improving child survival, further improvement in child health,
      especially in newborn health can be achieved if there is universal and equitable
      coverage of proven, quality health facility-based interventions. The magnitude of
      reduction in mortality will be similar to what has been achieved in the past
      decade. Strengthening health system to identify, understand, and direct resources
      to the poor and rural areas will ensure that Peru achieve the Sustainable
      Development Goals by 2030.

PMID- 27716136
TI  - Linking Swedish health data registers to establish a research database and a
      shared decision-making tool in hip replacement.
AB  - BACKGROUND: Sweden offers a unique opportunity to researchers to construct
      comprehensive databases that encompass a wide variety of healthcare related data.
      Statistics Sweden and the National Board of Health and Welfare collect individual
      level data for all Swedish residents that ranges from medical diagnoses to
      socioeconomic information. In addition to the information collected by
      governmental agencies the medical profession has initiated nationwide Quality
      Registers that collect data on specific diagnoses and interventions. The Quality
      Registers analyze activity within healthcare institutions, with the aims of
      improving clinical care and fostering clinical research. MAIN BODY: The Swedish
      Hip Arthroplasty Register (SHAR) has been collecting data since 1979. Joint
      replacement in general and hip replacement in particular is considered a success
      story with low mortality and complication rate. It is credited to the pioneering
      work of the SHAR that the revision rate following hip replacement surgery in
      Sweden is amongst the lowest in the world. This has been accomplished by the
      diligent follow-up of patients with feedback of outcomes to the providers of the
      healthcare along with post market surveillance of individual implant performance.
      During its existence SHAR has experienced a constant organic growth. One major
      development was the introduction of the Patient Reported Outcome Measures
      program, giving a voice to the patients in healthcare performance evaluation. The
      next aim for SHAR is to integrate patients' wishes and expectations with the
      surgeons' expertise in the form of a Shared Decision-Making (SDM) instrument. The
      first step in building such an instrument is to assemble the necessary data. This
      involves linking the SHARs database with the two aforementioned governmental
      agencies. The linkage is done by the 10-digit personal identity number assigned
      at birth (or immigration) for every Swedish resident. The anonymized data is
      stored on encrypted serves and can only be accessed after double identification.
      CONCLUSION: This data will serve as starting point for several research projects
      and clinical improvement work.

PMID- 27716137
TI  - Erratum to: Scaling-up an efficacious school-based physical activity
      intervention: Study protocol for the 'Internet-based Professional Learning to
      help teachers support Activity in Youth' (iPLAY) cluster randomized controlled
      trial and scale-up implementation evaluation.

PMID- 27716138
TI  - Comparing the mortality risks of nursing professionals with diabetes and general
      patients with diabetes: a nationwide matched cohort study.
AB  - BACKGROUND: Nursing professionals have received comprehensive medical education
      and training. However, whether these medical professionals exhibit positive
      patient care attitudes and behaviors and thus reduce mortality risks when they
      themselves are diagnosed with chronic diseases is worth exploring. This study
      compared the mortality risks of female nurses and general patients with diabetes
      and elucidated factors that caused this difference. METHODS: A total of 510,058
      female patients newly diagnosed with diabetes between 1998 and 2006 as recorded
      in the National Health Insurance Research Database were the participants in this
      study. Nurses with diabetes and general population with diabetes were matched
      with propensity score method in a 1:10 ratio. The participants were tracked from
      the date of diagnosis to 2009. The Cox proportional hazards model was utilized to
      compare the mortality risks in the two groups. RESULTS: Nurses were newly
      diagnosed with diabetes at a younger age compared with the general public (42.01
      +/- 12.03 y vs. 59.29 +/- 13.11 y). Nevertheless, the matching results showed
      that nurses had lower mortality risks (HR: 0.53, 95 % CI: 0.38-0.74) and nurses
      with diabetes in the < 35 and 35-44 age groups exhibited significantly lower
      mortality risks compared with general patients (HR: 0.23 and 0.36). A further
      analysis indicated that the factors that influenced the mortality risks of nurses
      with diabetes included age, catastrophic illnesses, and the severity of diabetes
      complications. CONCLUSION: Nurses with diabetes exhibited lower mortality risks
      possibly because they had received comprehensive medical education and training,
      may had more knowledge regarding chronic disease control and change their
      lifestyles. The results can serve as a reference for developing heath education,
      and for preventing occupational hazards in nurses.

PMID- 27716139
TI  - Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels
      in wastewater with sale, seizure and consumption data for 8 European cities.
AB  - BACKGROUND: Monitoring the scale of pharmaceuticals, illicit and licit drugs
      consumption is important to assess the needs of law enforcement and public
      health, and provides more information about the different trends within different
      countries. Community drug use patterns are usually described by national surveys,
      sales and seizure data. Wastewater-based epidemiology (WBE) has been shown to be
      a reliable approach complementing such surveys. METHOD: This study aims to
      compare and correlate the consumption estimates of pharmaceuticals, illicit
      drugs, alcohol, nicotine and caffeine from wastewater analysis and other sources
      of information. Wastewater samples were collected in 2015 from 8 different
      European cities over a one week period, representing a population of
      approximately 5 million people. Published pharmaceutical sale, illicit drug
      seizure and alcohol, tobacco and caffeine use data were used for the comparison.
      RESULTS: High agreement was found between wastewater and other data sources for
      pharmaceuticals and cocaine, whereas amphetamines, alcohol and caffeine showed a
      moderate correlation. methamphetamine and 3,4-methylenedioxymethamphetamine
      (MDMA) and nicotine did not correlate with other sources of data. Most of the
      poor correlations were explained as part of the uncertainties related with the
      use estimates and were improved with other complementary sources of data.
      CONCLUSIONS: This work confirms the promising future of WBE as a complementary
      approach to obtain a more accurate picture of substance use situation within
      different communities. Our findings suggest further improvements to reduce the
      uncertainties associated with both sources of information in order to make the
      data more comparable.

PMID- 27716140
TI  - Longitudinal survey of Clostridium difficile presence and gut microbiota
      composition in a Belgian nursing home.
AB  - BACKGROUND: Increasing age, several co-morbidities, environmental contamination,
      antibiotic exposure and other intestinal perturbations appear to be the greatest
      risk factors for C. difficile infection (CDI). Therefore, elderly care home
      residents are considered particularly vulnerable to the infection. The main
      objective of this study was to evaluate and follow the prevalence of C. difficile
      in 23 elderly care home residents weekly during a 4-month period. A C. difficile
      microbiological detection scheme was performed along with an overall microbial
      biodiversity study of the faeces content by 16S rRNA gene analysis. RESULTS:
      Seven out of 23 (30.4 %) residents were (at least one week) positive for C.
      difficile. C. difficile was detected in 14 out of 30 diarrhoeal samples (43.7 %).
      The most common PCR-ribotype identified was 027. MLVA showed that there was a
      clonal dissemination of C. difficile strains within the nursing home residents.
      16S-profiling analyses revealed that each resident has his own bacterial imprint,
      which was stable during the entire study. Significant changes were observed in C.
      difficile positive individuals in the relative abundance of a few bacterial
      populations, including Lachnospiraceae and Verrucomicrobiaceae. A decrease of
      Akkermansia in positive subjects to the bacterium was repeatedly found.
      CONCLUSIONS: A high C. difficile colonisation in nursing home residents was
      found, with a predominance of the hypervirulent PCR-ribotype 027. Positive C.
      difficile status is not associated with microbiota richness or biodiversity
      reduction in this study. The link between Akkermansia, gut inflammation and C.
      difficile colonisation merits further investigations.

PMID- 27716141
TI  - Multi-omics analysis reveals regulators of the response to PDGF-BB treatment in
      pulmonary artery smooth muscle cells.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a lethal disease with
      pronounced narrowing of pulmonary vessels due to abnormal cell proliferation. The
      platelet-derived growth factor BB (PDGF-BB) is well known as a potent mitogen for
      smooth muscle cell proliferation. To better understand how this growth factor
      regulates pulmonary arterial smooth muscle cells (PASMCs) proliferation, we
      sought to characterize the response to PDGF-BB stimulation at system-wide levels,
      including the transcriptome and proteome. RESULTS: In this study, we identified
      1611 mRNAs (transcriptome), 207 proteins (proteome) differentially expressed in
      response to PDGF-BB stimulation in PASMCs based on RNA-sequencing and isobaric
      tags for relative and absolute quantification (iTRAQ) assay. Transcription factor
      (TF)-target network analysis revealed that PDGF-BB regulated gene expression
      potentially via TFs including HIF1A, JUN, EST1, ETS1, SMAD1, FOS, SP1, STAT1,
      LEF1 and CEBPB. Among them, SMAD1-involved BMPR2/SMADs axis plays a significant
      role in PAH development. Interestingly, we observed that the expression of BMPR2
      was decreased in both mRNA and protein level in response to PDGF-BB. Further
      study revealed that BMPR2 is the direct target of miR-376b that is up-regulated
      upon PDGF-BB treatment. Finally, EdU incorporation assay showed that miR-376b
      promoted proliferation of PASMCs. CONCLUSION: This integrated analysis of PDGF-BB
      regulated transcriptome and proteome was performed for the first time in normal
      PASMCs, which revealed a crosstalk between PDGF signaling and BMPR2/SMADs axis.
      Further study demonstrated that PDGF-BB-induced miR-376b upregulation mediated
      the downregulation of BMPR2, which led to expression change of its downstream
      targets and promoted proliferation of PASMCs.

PMID- 27716142
TI  - Successful customer intercept interview recruitment outside small and midsize
      urban food retailers.
AB  - BACKGROUND: Customer intercept interviews are increasingly used to characterize
      food purchases at retail food outlets and restaurants; however, methodological
      procedures, logistical issues and response rates using intercept methods are not
      well described in the food environment literature. The aims of this manuscript
      were to 1) describe the development and implementation of a customer intercept
      interview protocol in a large, NIH-funded study assessing food purchases in small
      and midsize food retailers in Minneapolis and St. Paul, Minnesota, 2) describe
      intercept interview response rates by store type and environmental factors (e.g.,
      neighborhood socioeconomic status, day/time, weather), and 3) compare demographic
      characteristics (e.g., gender, race/ethnicity) of participants versus non
      participants. METHODS: After a pilot phase involving 28 stores, a total of 616
      interviews were collected from customers exiting 128 stores in fall 2014. The
      number of eligible customers encountered per hour (a measure of store traffic),
      participants successfully recruited per hour, and response rates were calculated
      overall and by store type, neighborhood socio-economic status, day and time of
      data collection, and weather. Response rates by store type, neighborhood socio
      economic status, time and day of data collection, and weather, and
      characteristics of participants and non-participants were compared using chi
      square tests. RESULTS: The overall response rate was 35 %, with significantly
      higher response rates at corner/small grocery stores (47 %) and dollar stores (46
      %) compared to food-gas marts (32 %) and pharmacies (26 %), and for data
      collection between 4:00-6:00 pm on weekdays (40 %) compared to weekends (32 %).
      The distribution of race/ethnicity, but not gender, differed between participants
      and non-participants (p < 0.01), with greater participation rates among those
      identified as Black versus White. CONCLUSIONS: Customer intercept interviews can
      be successfully used to recruit diverse samples of customers at small and midsize
      food retailers. Future community-based studies using customer intercept
      interviews should collect data sufficient to report response rates and consider
      potential differences between the racial/ethnic composition of the recruited
      sample and the target population.

PMID- 27716143
TI  - Reduced representation bisulphite sequencing of ten bovine somatic tissues
      reveals DNA methylation patterns and their impacts on gene expression.
AB  - BACKGROUND: As a major epigenetic component, DNA methylation plays important
      functions in individual development and various diseases. DNA methylation has
      been well studied in human and model organisms, but only limited data exist in
      economically important animals like cattle. RESULTS: Using reduced representation
      bisulphite sequencing (RRBS), we obtained single-base-resolution maps of bovine
      DNA methylation from ten somatic tissues. In total, we evaluated 1,868,049
      cytosines in CG-enriched regions. While we found slightly low methylation levels
      (29.87 to 38.06 %) in cattle, the methylation contexts (CGs and non-CGs) of
      cattle showed similar methylation patterns to other species. Non-CG methylation
      was detected but methylation levels in somatic tissues were significantly lower
      than in pluripotent cells. To study the potential function of the methylation, we
      detected 10,794 differentially methylated cytosines (DMCs) and 836 differentially
      methylated CG islands (DMIs). Further analyses in the same tissues revealed many
      DMCs (including non-CGs) and DMIs, which were highly correlated with the
      expression of genes involved in tissue development. CONCLUSIONS: In summary, our
      study provides a baseline dataset and essential information for DNA methylation
      profiles of cattle.

PMID- 27716144
TI  - Prevalence of osteoporosis in China: a meta-analysis and systematic review.
AB  - BACKGROUND: We conducted a systematic review and meta-analysis to obtain a
      reliable estimation of the prevalence of osteoporosis in China and to
      characterize its epidemiology. METHODS: We identified relevant studies via a
      search of literature published from 2003 to October 2015 in the PubMed, Web of
      Science, China National Knowledge Infrastructure, Wanfang and Weipu databases.
      Both Chinese and WHO criteria were considered acceptable for the diagnosis of
      osteoporosis. Prevalence estimates were obtained using random effects models.
      Meta-regression analysis was used to explore the sources of heterogeneity, and
      publication bias was evaluated by visually inspecting funnel plots. RESULTS:
      Overall, 69 articles were included in this study. An obvious increase in the
      prevalence of osteoporosis was identified over the past 12 years (prevalence of
      14.94 % before 2008 and 27.96 % during the period spanning 2012-2015). The
      prevalence of osteoporosis was higher in females than in males (25.41 % vs. 15.33
      %) and increased with age. Osteoporosis prevalence was higher in rural than in
      urban areas (20.87 % vs. 23.92 %) and higher in southern than in northern areas
      (23.17 % vs. 20.13 %). At present, the pooled prevalence of osteoporosis in
      people aged 50 years and older was more than twice the pooled prevalence
      identified in 2006 (34.65 % vs. 15.7 %). The application of different diagnostic
      criteria could have an impact on prevalence estimation (19.7 % vs. 29.3 %). Meta
      regression suggested that study setting also influenced the estimation of point
      prevalence (P = 0.022). CONCLUSIONS: The prevalence of osteoporosis in China has
      increased over the past 12 years, affecting more than one-third of people aged 50
      years and older. The prevalence of osteoporosis increased with age and was higher
      in females than in males. Prevention and control measures have become all the
      more important given the increase in osteoporosis prevalence, and three-step
      prevention programmes should be implemented.

PMID- 27716146
TI  - The effect of war on infant mortality in the Democratic Republic of Congo.
AB  - BACKGROUND: The Democratic Republic of Congo (DRC) has suffered from war and
      lingering conflicts in East DRC and has one of the highest infant mortality rates
      in the world. Prior research has documented increases in infant and child
      mortality associated with war, but the empirical evidence is limited in several
      respects. Measures of conflict are quite crude or conflict is not tightly linked
      to periods of exposure to infant death. Few studies have distinguished between
      the effects of war on neonatal versus post-neonatal infants. No study has
      considered possible differences between women who give birth during wartime and
      those who do not that may be related to greater infant mortality. METHODS: The
      analysis used the nationally representative sample of 15,103 mothers and 53,768
      children from the 2007 and 2013/2014 Demographic Health Survey in the DRC and
      indicators of conflict events and conflict deaths from the 2013 Uppsala Conflict
      Data. To account for unobserved heterogeneity across women, a multi-level
      modeling approach was followed by grouping all births for each woman and
      estimating random intercepts in discrete time event history models. RESULTS: Post
      neonatal mortality increased during the Congolese wars, and was highest where
      conflict events and deaths were extreme. Neonatal mortality was not associated
      with conflict levels. Infant mortality was not higher in East DRC, where
      conflicts continued during the post Congolese war period. Models specifying
      unobserved differences between mothers who give birth during war and those who
      have children in peacetime did not reduce the estimated effect of war, i.e., no
      support was found for selectivity in the sample of births during war. CONCLUSION:
      Differences in effects of the Congolese war on neonatal versus post-neonatal
      mortality suggest that conflict influences the conditions of infants' lives more
      than the aspects of mothers' pregnancy conditions and delivery that are relevant
      for infant mortality. These differences may, however, be specific to the nature
      of conflict and prior conditions in the DRC. Because of continued political
      instability, violent conflict may be expected to continue in contexts such as the
      DRC; we must therefore continue to document, analyze and monitor the mechanisms
      through which war influences infant mortality.

PMID- 27716145
TI  - Kidney function is associated with severity of white matter hyperintensity in
      patients with acute ischemic stroke/TIA.
AB  - BACKGROUND: Previous studies suggested the potential interactions between
      cerebrovascular diseases and impaired renal function. However, the relationship
      between renal function and white matter hyperintensity (WMH), marker of cerebral
      small vessel disease, in patients with acute ischemic stroke (AIS) or transient
      ischemic attack (TIA) remains unknown. METHODS: We consecutively enrolled 1632
      subjects with AIS or TIA who underwent brain MRI for this analysis. The severity
      of WMH in both of periventricular (PVH) and deep subcortical white matter (SDWMH)
      was evaluated using Fazekas scale. Estimated glomerular filtration rate (eGFR)
      was calculated by the equation of the Modification Diet for Renal Disease.
      Multinomial logistic regression was performed to evaluate the association between
      the severity of WMH and eGFR. RESULTS: Advanced age and hypertension were
      independently associated with the severity of both PVH and SDWMH (all p < 0.001).
      There is a significantly inverse association between eGFR and PVH. Patients
      having each 30 ml/min/1.73 m2 increase in eGFR was associated with 75 % of risk
      of having degree 3 of WMH in periventricular areas compared with degree 0 (p =
      0.04, OR = 0.75, 95 % CI 0.61-0.92). However this inverse association was not
      found between eGFR and SDWMH (P = 0.50, OR = 0.93, 95 % CI0.75-1.14). CONCLUSION:
      Our study demonstrates that renal dysfunction (eGFR) is independently associated
      with the severity of PVH but not SDWMH in patients with acute ischemic stroke.
      This results highlighted different pathological mechanism and risk factors of PVH
      and SDWMH.

PMID- 27716147
TI  - Two colliding epidemics - obesity is independently associated with chronic pain
      interfering with activities of daily living in adults 18 years and over; a cross
      sectional, population-based study.
AB  - BACKGROUND: Chronic pain interfering with activities of daily living is highly
      prevalent in the community. More than 600 million people worldwide are obese. The
      aim of this paper is to assess if such chronic pain is associated independently
      with obesity across the adult population, having controlled for other key
      factors. METHODS: The South Australian Health Omnibus is an annual, population
      based, cross-sectional study. Data on 2616 participants were analysed for
      episodes of daily pain for three of the preceding six months. Obesity was derived
      from self-reported height and weight. Multivariable logistic regression analysed
      the associations between chronic pain interfering with activities of daily
      living, body mass index (BMI) and key socio-demographic factors. RESULTS: Chronic
      pain interfering with activities of daily living peaks in people >=75 years of
      age while obesity peaks in the 45-54 age group. Pain and obesity together peak in
      the 55-74 year age group. In the adjusted multinominal logistic regression model,
      compared to those with no pain, there was a strong association between obesity
      and pain that interfered moderately or extremely with day-to-day activities (OR
      2.25; 95 % CI 1.57-3.23; p < 0.001) having controlled for respondents' age,
      gender, rurality, country of birth and highest educational attainment. People
      over 65 years of age and those with lower educational levels were more likely to
      experience such chronic pain related to obesity. CONCLUSION: This study
      demonstrates a strong association between chronic pain and obesity/morbid obesity
      in the South Australian population. Prospective, longitudinal data are needed to
      understand the dynamic interaction between these two prevalent conditions.

PMID- 27716148
TI  - Cirrhosis related functionality characteristic of the fecal microbiota as
      revealed by a metaproteomic approach.
AB  - BACKGROUND: Intestinal microbiota operated as a whole and was closely related
      with human health. Previous studies had suggested close relationship between
      liver cirrhosis (LC) and gut microbiota. METHODS: To determine the functional
      characteristic of the intestinal microbiota specific for liver cirrhosis, the
      fecal metaproteome of three LC patients with Child-Turcotte-Pugh (CTP) score of
      A, B, and C, and their spouse were first compared using high-throughput approach
      based on denaturing polyacrylamide gel electrophoresis and liquid chromatography
      tandem mass spectrometry in our study. RESULTS: A total of 5,020 proteins (88 %
      from bacteria, 12 % form human) were identified and annotated based on the GO and
      KEGG classification. Our results indicated that the LC patients possessed a core
      metaproteome including 119 proteins, among which 14 proteins were enhanced
      expressed and 7 proteins were unique for LC patients compared with the normal,
      which were dominant at the function of carbohydrate metabolism. In addition, LC
      patients have unique biosynthesis of branched chain amino acid (BCAA),
      pantothenate, and CoA, enhanced as CTP scores increased. Those three substances
      were all important in a wide array of key and essential biological roles of life.
      CONCLUSIONS: We observed a highly comparable cirrhosis-specific metaproteome
      clustering of fecal microbiota and provided the first supportive evidence for the
      presence of a LC-related substantial functional core mainly involved in
      carbohydrate, BCAA, pantothenate, and CoA metabolism, suggesting the compensation
      of intestinal microbiota for the fragile and innutritious body of cirrhotic
      patients.

PMID- 27716149
TI  - The effects of AST-120 on chronic kidney disease progression in the United States
      of America: a post hoc subgroup analysis of randomized controlled trials.
AB  - BACKGROUND: The orally administered spherical carbon adsorbent AST-120 is used on
      label in Asian countries to slow renal disease progression in patients with
      progressive chronic kidney disease (CKD). Recently, two multinational,
      randomized, double-blind, placebo-controlled, phase 3 trials (Evaluating
      Prevention of Progression in Chronic Kidney Disease [EPPIC] trials) examined AST
      120's efficacy in slowing CKD progression. This study assessed the efficacy of
      AST-120 in the subgroup of patients from the United States of America (USA) in
      the EPPIC trials. METHODS: In the EPPIC trials, 2035 patients with moderate to
      severe CKD were studied, of which 583 were from the USA. The patients were
      randomly assigned to two groups of equal size that were treated with AST-120 or
      placebo (9 g/day). The primary end point was a composite of dialysis initiation,
      kidney transplantation, or serum creatinine doubling. RESULTS: The Kaplan-Meier
      curve for the time to achieve the primary end point in the placebo-treated
      patients from the USA was similar to that projected before the study. The per
      protocol subgroup analysis of the population from the USA which included patients
      with compliance rates of >=67 % revealed a significant difference between the
      treatment groups in the time to achieve the primary end point (Hazard Ratio,
      0.74; 95 % Confidence Interval, 0.56-0.97). CONCLUSIONS: This post hoc subgroup
      analysis of EPPIC study data suggests that treatment with AST-120 might delay the
      time to primary end point in CKD patients from the USA. A further randomized
      controlled trial in progressive CKD patients in the USA is necessary to confirm
      the beneficial effect of adding AST-120 to standard therapy regimens. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00500682 ; NCT00501046 .

PMID- 27716150
TI  - Prevalence of short stature, underweight, overweight, and obesity among school
      children in Jordan.
AB  - BACKGROUND: The prevalence of short stature (SS) and underweight in Jordan on a
      national level is unknown. This study aimed to investigate, on a national level,
      the prevalence of short stature (SS), underweight, overweight, and obesity among
      school aged children in Jordan. METHODS: This cross-sectional study was conducted
      from May 2015 to January 2016 and included 2702 subjects aged 6-17 years. Jordan
      was classified into 3 regions; North, Center (urban), and South (rural). Public
      and private schools were randomly selected from a random sample of cities from
      each region. The socioeconomic status of the sampling locations was assessed
      using several indicators including education, income, healthcare and housing
      conditions. For each participating subject, anthropometrics were obtained. SS,
      underweight, overweight and obesity were defined using Center of Disease
      Control's (CDC) growth charts. Median Z-scores for each region, age and gender
      were calculated. RESULTS: The Central and Northern regions enjoyed higher
      socioeconomic status compared to rural Southern regions. The overall prevalence
      of SS, underweight, overweight, and obesity were 4.9 %, 5.7 %, 17.3 %, and 15.7
      %, respectively. SS and underweight were most prevalent in the rural South, while
      obesity was highest in the Central region. Females were more likely to be
      overweight, while males were more likely to be obese. Private schools had higher
      prevalence of obesity and overweight than public ones. CONCLUSIONS: Variations in
      height and weight among Jordanian school children might be affected by
      socioeconomic status.

PMID- 27716151
TI  - The associations between domain-specific sedentary behaviours and dietary habits
      in European adults: a cross-sectional analysis of the SPOTLIGHT survey.
AB  - BACKGROUND: Sedentary behaviour has been associated with obesity and related
      chronic diseases. Disentangling the nature of this association is complicated due
      to interactions with other lifestyle factors, such as dietary habits, yet limited
      research has investigated the relation between domain-specific sedentary
      behaviours and dietary habits in adults. The aim of this paper was to examine the
      association between domain-specific sedentary behaviours and dietary habits in
      adults and to test the moderating effect of age and gender on this association.
      METHODS: A total of 6,037 participants from five urban regions in Europe
      completed an online survey, of which 6,001 were included in the analyses.
      Multilevel mixed-effects logistic regression analyses were used to examine main
      associations and interaction effects. RESULTS: All domain-specific sedentary
      behaviours, except transport-related sitting time, were significantly related to
      dietary habits. In general, having a higher sitting time was related to having
      less healthy dietary habits, especially for television viewing. Gender did not
      moderate any of the relations, and age was only a significant moderator in the
      relation between other leisure sitting time and alcohol consumption. CONCLUSION:
      Domain-specific sitting behaviours were related to unhealthy dietary behaviours.
      However, the small effect sizes suggest that individual level behavioural
      interventions focusing on sedentary behaviour will not be sufficient to improve
      dietary habits. The fact that almost none of the associations were moderated by
      age or gender suggests that these associations, and possibly also the effects of
      interventions targeting both behaviours, may hold across age and gender groups.

PMID- 27716153
TI  - Evaluation of bond strength of various epoxy resin based sealers in oval shaped
      root canals.
AB  - BACKGROUND: The aim of this study was to evaluate the bond strength of AH plus,
      Acroseal, and Adseal to the root canal dentin. METHODS: A total of 36 single
      rooted, mandibular premolar teeth were used. Root canal shaping procedures were
      performed with ProTaper rotary instruments (Dentsply Maillefer) up to size F4.
      The prepared samples were then randomly assembled into 3 groups (n = 12). For
      each group, an ultrasonic tip (size 15, 0.02 taper) which was also coated with an
      epoxy resin based sealer and placed 2 mm shorter than the working length. The
      sealer was then activated for 10 s. A push-out test was used to measure the bond
      strength between the root canal dentine and the sealer. Kruskal-Wallis test to
      evaluate the push-out bond strength of epoxy based sealer (P = 0.05). The failure
      mode data were statistically analyzed using Pearson's chi square test (P = 0.05).
      RESULTS: Kruskal-Wallis test indicated that there were no statistically
      significant difference among the push out bond strength values of 3 mm (p =
      0.123) and 6 mm (P = 0.057) for groups, there was statistically significant
      difference push out bond strength value of 9 mm (P = 0.032). Pearson's chi square
      test showed statistically significant differences for the failure types among the
      groups. CONCLUSION: Various epoxy resin based sealers activated ultrasonically
      showed similar bond strength in oval shaped root canals. Apical sections for all
      groups have higher push out bond strength values than middle and coronal
      sections.

PMID- 27716152
TI  - Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a
      randomized, placebo-controlled trial to determine if low-dose carvedilol can
      prevent anthracycline-related left ventricular remodeling in childhood cancer
      survivors at high risk for developing heart failure.
AB  - BACKGROUND: Anthracyclines are widely used in the treatment of childhood cancer.
      One of the well-recognized side-effects of anthracycline therapy is dose
      dependent cardiomyopathy that may progress to heart failure (HF) years after
      completion of cancer-directed therapy. This study will evaluate the efficacy of
      low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer
      survivors at highest risk for HF. The proposed intervention has the potential to
      significantly reduce chronic cardiac injury via interruption of neurohormonal
      systems responsible for left ventricular (LV) remodeling, resulting in improved
      cardiac function and decreased risk of HF. The intervention is informed by
      previous studies demonstrating efficacy in pediatric and adult non-oncology
      populations, yet remains unstudied in the pediatric oncology population.
      METHODS/DESIGN: The primary objective of the trial is to determine impact of the
      intervention on echocardiographic markers of cardiac remodeling and HF risk,
      including: LV wall thickness/ dimension ratio (LVWT/D; primary endpoint), as well
      as LV ejection fraction, volume, and blood biomarkers (natriuretic peptides,
      galectin-3) associated with HF risk. Secondary objectives are to establish safety
      and tolerability of the 2-year course of carvedilol using: 1) objective measures:
      hepatic and cardiovascular toxicity, treatment adherence, and 2) subjective
      measures: participant self-reported outcomes. Two hundred and fifty survivors of
      childhood cancer (diagnosed <21 years of age), and previously treated with high
      dose (>=300 mg/m2) anthracyclines will be enrolled in a randomized, double-blind,
      placebo controlled trial. After baseline assessments, participants will be
      randomized in a 1:1 ratio to low-dose carvedilol (maximum dose: 12.5 mg/day) or
      placebo. Carvedilol or placebo is up-titrated (starting dose: 3.125 mg/day)
      according to tolerability. DISCUSSION: When completed, this study will provide
      much-needed information regarding a physiologically plausible pharmacological
      risk-reduction strategy for childhood cancer survivors at high risk for
      developing anthracycline-related HF. TRIAL REGISTRATION: ClinicalTrials.gov;
      NCT02717507.

PMID- 27716154
TI  - Effect of the herbal mixture composed of Aloe Vera, Henna, Adiantum capillus
      veneris, and Myrrha on wound healing in streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Wound healing is often impaired in diabetic animals and humans.
      Matrix metalloproteases act as pro-inflammatory agents in physiological wound
      healing pathways by stimulating cytokines including the interleukins, IL6, IL1A
      and IL1B, and the tumor necrosis factor and transforming growth factor beta1.
      Botanicals are traditionally used to assist healing of different types of wounds,
      because they produce fewer side effects. Our specific aim here was to develop a
      plant-based recipe supporting effective wound healing in diabetic animals.
      METHODS: Plant materials from Adiantum capillus-veneris, Commiphora molmol, Aloe
      Vera, and henna were collected for this study, and oven-dried at 60  degrees C.
      The dried leaves and resins were then crumbled into a powder and mixed in equal
      parts with Vaseline as a preservative. This mixture was used as an ointment on
      wounds induced in 60 diabetic and non-diabetic rats that were divided into 6
      subgroups receiving agent or control treatments. Necrotic tissue surrounding the
      wound was periodically removed during wound healing. RNA was extracted from the
      healing region of the wound at days 7, 14 and 21 for cDNA synthesis to monitor
      changes in Tgfb1, Mmp3, Mmp9, Il6 and Tnf alpha expression using real-time PCR.
      RESULTS: The expression of the Mmp3, the Tnf alpha, and the Tgfb1 genes from
      wound tissue were significantly different (p < 0.05) between diabetic and non
      diabetic (control) rats treated with the herbal mixture after 14 and 21 days.
      There was no significant difference (p > 0.05) of the Mmp9 gene expression in
      diabetic and non-diabetic rats treated only with Vaseline after 7, 14, and 21
      days. But, the expression of the Mmp9 gene decreased significantly (p < 0.05) in
      diabetic rats after 14 days in comparison to non-diabetic rats, when the herbal
      mixture was added to Vaseline. CONCLUSIONS: Our study presents an herbal
      treatment that alters the gene expression signature at wounds induced in the rat
      model for type I diabetes in a manner consistent with accelerated healing, and
      demonstrates that this herbal treatment might be effective to treat wounds in
      diabetic patients.

PMID- 27716155
TI  - Specialty preferences among final year medical students in medical schools of
      southeast Nigeria: need for career guidance.
AB  - BACKGROUND: In resource-poor settings with low doctor-population ratio, there is
      need for equitable distribution of healthcare workforce. The specialty
      preferences of medical students determine the future composition of physician
      workforce hence its relevance in career guidance, healthcare planning and policy
      formulation. This study was aimed at determining the specialty preferences of
      final year medical students in medical schools of southeast Nigeria, the gender
      differences in choice of specialty and the availability of career guidance to the
      students during the period of training. METHODS: A descriptive cross-sectional
      study was conducted among final year medical students in the six accredited
      medical schools in southeast Nigeria using self-administered semi-structured
      questionnaire. Information on reason for studying Medicine, specialty preference
      and career guidance were obtained. Chi-square test of statistical significance
      was used in the analysis. RESULTS: A total of 457 students participated in the
      study with a response rate of 86.7 %. The mean age was 25.5 +/- 2.9 years and
      57.1 % were male. Majority (51 %) opted to study Medicine in-order to save lives
      while 89.5 % intended to pursue postgraduate medical training. A higher
      proportion (51.8 %) made the decision during the period of clinical rotation. The
      five most preferred specialties among the students were Surgery (24.0 %);
      Paediatrics (18.8 %); Obstetrics and Gynaecology (15.6 %); Internal Medicine
      (11.0 %) and Community Medicine (6.8 %) while Pathology (2.0 %); Anaesthesia (0.7
      %) and Ear, Nose and Throat (0.2 %), were the least preferred. Compared to
      females, a higher proportion of male students intended to specialise in Surgery
      (32.3 % vs 13.0 %, p < 0.001) in contrast to Paediatrics (11.2 % vs 28.8 %, p <
      0.001). Majority of the students, 74.6 % had no form of career guidance during
      their stay in medical school and 11.2 % were undecided on choice of specialty.
      CONCLUSION: In spite of the high proportion of students willing to pursue
      specialist medical training after graduation, most opted for the four core
      clinical specialities of Surgery, Paediatrics, Obstetrics and Gynaecology and
      Internal Medicine. Majority of the students made these decisions during clinical
      rotations. Also, majority had no form of career guidance throughout their stay in
      medical school. To ensure an equitable distribution of a limited physician
      workforce in a resource-poor setting, there is need for proper career guidance
      for the students and this should be in line with the national health needs.

PMID- 27716156
TI  - An empirical study of the 'underscreened' in organised cervical screening:
      experts focus on increasing opportunity as a way of reducing differences in
      screening rates.
AB  - BACKGROUND: Cervical cancer disproportionately burdens disadvantaged women.
      Organised cervical screening aims to make cancer prevention available to all
      women in a population, yet screening uptake and cancer incidence and mortality
      are strongly correlated with socioeconomic status (SES). Reaching underscreened
      populations is a stated priority in many screening programs, usually with an
      emphasis on something like 'equity'. Equity is a poorly defined and understood
      concept. We aimed to explain experts' perspectives on how cervical screening
      programs might justifiably respond to 'the underscreened'. METHODS: This paper
      reports on a grounded theory study of cervical screening experts involved in
      program organisation. Participants were 23 experts from several countries and a
      range of backgrounds: gynecology; epidemiology; public health; pathology; general
      practice; policy making. Data were gathered via semi-structured interview and
      concepts developed through transcript coding and memo writing. RESULTS: Most
      experts expressed an intuitive commitment to reducing systematic differences in
      screening participation or cancer outcomes. They took three different implicit
      positions, however, on what made organised programs justifiable with respect to
      underscreened populations. These were: 1) accepting that population screening is
      likely to miss certain disenfranchised groups for practical and cultural reasons,
      and focusing on maximising mainstream reach; 2) identifying and removing barriers
      to screening; and 3) providing parallel tailored screening services that attended
      to different cultural needs. Positions tended to fall along country of practice
      lines. CONCLUSIONS: Experts emphasised the provision of opportunity for
      underscreened populations to take up screening. A focus on opportunity appeared
      to rely on tacit premises not supported by evidence: that provision of meaningful
      opportunity leads to increased uptake, and that increased uptake of an initial
      screening test by disadvantaged populations would decrease cervical cancer
      incidence and mortality. There was little attention to anything other than the
      point of testing, or the difficulties disadvantaged women can have in accessing
      follow up care. The different approaches to 'improving equity' taken by
      participants are differently justified, and differently justifiable, but none
      attend directly to the broader conditions of disadvantage.

PMID- 27716157
TI  - Effects of a fixed low-dose ropivacaine with different volume and concentrations
      on interscalene brachial plexus block: a randomized controlled trial.
AB  - BACKGROUND: Ultrasound guidance has reduced the amount of local anesthetics to
      achieve a successful block. Previous studies of the relationship between the
      volume or concentration of local anesthetics and the effects of the block were
      based on relatively high doses of local anesthetics. We tested the hypothesis
      that providing low dose of ropivacaine at three combinations of volumes and
      concentrations for ultrasound-guided interscalene brachial plexus block would
      produce different effects in the aspect of onset time, pain control and the
      incidence of side effects. METHODS: Ninety-nine patients undergoing elective
      arthroscopic shoulder surgery were randomized to receive an ultrasound guided
      combined with nerve stimulator mediated interscalene block with ropivacaine 0.75
      % (6.7 ml, Group 0.75), 0.5 % (10 ml, Group 0.5) or 0.25 % (20 ml, Group 0.25).
      The primary end point was the onset time of the sensory blockade, assessed by
      using a pinprick in the C5-6 dermatome. The secondary end points included the
      onset time of the motor blockade, block success rate, postoperative pain rating
      score, rescue analgesics requirement, sleep quality, strength of the hand on the
      block side,and the incidence of hemi-diaphragmatic paresis which was evaluated by
      ultrasonography. RESULTS: There was a statistically significant difference of the
      sensory block median onset times among Group 0.75 (5 min), Group 0.5 (10 min) and
      Group 0.25 (20 min). One patient in Group 0.5 and 20 patients in Group 0.25 did
      not achieve a complete motor block within 30 min, which were also significantly
      different. No significant difference was observed in postoperative analgesia,
      decrease of handgrip strength and the incidence of hemi-diaphragmatic paresis
      among the 3 groups. CONCLUSIONS: This study demonstrates that ropivacaine 50 mg
      as 0.25, 0.5 or 0.75 % solution for interscalene brachial plexus block before
      arthroscopic shoulder surgery produces comparable blockade with few side effects,
      while 0.75 % seems to be more preferable as it is associated with faster onset
      time. TRIAL REGISTRATION: ChiCTR-TRC-13004058 . Registered 4 December 2013.

PMID- 27716158
TI  - Effect of chondroitin sulfate on soluble biomarkers of osteoarthritis: a method
      to analyze and interpret the results from an open-label trial in unilateral knee
      osteoarthritis patients.
AB  - BACKGROUND: The aim of this study was to investigate the effects of chondroitin
      sulfate (CS) on the serum levels of Coll2-1 in patients with knee OA. METHODS:
      Seventy two patients with unilateral symptomatic knee OA were involved in a post
      authorization open-label study evaluating CS (800 mg/day). The primary outcome
      was the % relative change in serum Coll2-1 (sColl2-1). The secondary outcomes
      were the evaluation of pain (VAS) and function (Lequesne's Index). Responders and
      non-responders were classified according to OMERACT-OARSI recommendations.
      Finally, an original cut-off method was applied to categorize patients and
      interpret individual variations in serum levels of Coll2-1. RESULTS: Patients
      showed no difference in the sColl2-1 levels at baseline. When considering
      responders and non-responders from the ITT population, a significant difference
      was found for Coll2-1 at 3 months (p = 0.030) and 6 months (p = 0.038). A
      decrease in pain (VAS) and an improvement in function (LI) were recorded
      throughout the visits (p < 0.01). Considering an intra-batch cut-off of 21 %, CS
      decreased Coll2-1 serum levels between baseline and 1-month visit compared to the
      value of Coll2-1 before treatment (screening visit) which can be interpreted as a
      drastic reduction of the proportion of patients with an increase of Coll2-1 over
      21 % (reduction from 13 to 3 %). It also consisted in a more important proportion
      of patients with a decrease in Coll2-1 (from 5 to 10 %). CONCLUSION: This study
      proposes a new approach for the analysis and the interpretation of the individual
      variation in biomarker levels and introduces the notion of metabolic responders.
      TRIAL REGISTRATION: ID ISRCTN63795830 . The trial was retrospectively registered
      on 2 October, 2015.

PMID- 27716160
TI  - Extracts of six Rubiaceae species combined with rifampicin have good in vitro
      synergistic antimycobacterial activity and good anti-inflammatory and antioxidant
      activities.
AB  - BACKGROUND: The Rubiaceae family has played a significant role in drug discovery
      by providing molecules with potential use as templates for the development of
      therapeutic drugs. This study was designed to study the in vitro synergistic
      effect of six Rubiaceae species in combination with a known anti-TB drug. The
      antioxidant and anti-inflammatory activity of these species were also evaluated
      to investigate additional benefits in antimycobacterial treatment. METHODS: The
      checkerboard method was used to determine the antimycobacterial synergistic
      activity of plant extracts combined with rifampicin. The antioxidant activity of
      extracts was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Anti
      inflammatory activity via inhibition of nitric oxide (NO) production was
      performed in LPS-activated RAW 264.7 macrophages using the Griess assay. RESULTS:
      Combination of rifampicin with the crude extracts resulted in a 4 to 256-fold
      increase of activity of extracts. The crude extract of Cremaspora triflora
      produced the best synergistic effect with rifampicin, with a fractional
      inhibitory concentration (FIC) index of 0.08 against Mycobacterium aurum.
      Extracts of Psychotria zombamontana had the best antioxidant activity with an
      IC50 value of 1.77 MUg/mL, lower than the IC50 of trolox and ascorbic acid (5.67
      MUg/mL and 4.66 MUg/mL respectively). All the extracts tested inhibited nitric
      oxide (NO) production in a concentration dependent manner with the percentage of
      inhibition varying from 6.73 to 86.27 %. CONCLUSION: Some of the Rubiaceae
      species investigated have substantial in vitro synergistic effects with
      rifampicin and also good free radical scavenging ability and anti-inflammatory
      activity. These preliminary results warrant further study on these plants to
      determine if compounds isolated from these species could lead to the development
      of bioactive compounds that can potentiate the activity of rifampicin even
      against resistant mycobacteria.

PMID- 27716161
TI  - Using program evaluation to support knowledge translation in an interprofessional
      primary care team: a case study.
AB  - BACKGROUND: Evaluation is a fundamental component in building quality primary
      care and is ideally situated to support individual, team and organizational
      learning by offering an accessible form of participatory inquiry. The evaluation
      literature has begun to recognize the unique features of KT evaluations and has
      described attributes to consider when evaluating KT activities. While both
      disciplines have focused on the evaluation of KT activities neither has explored
      the role of evaluation in KT. The purpose of the paper is to examine how
      participation in program evaluation can support KT in a primary care setting.
      METHODS: A mixed methods case study design was used, where evaluation was
      conceptualized as a change process and intervention. A Memory Clinic at an
      interprofessional primary care clinic was the setting in which the study was
      conducted. An evaluation framework, Pathways of Influence provided the
      theoretical foundation to understand how program evaluation can facilitate the
      translation of knowledge at the level of the individual, inter-personal (Memory
      Clinic team) and the organization. Data collection included questionnaires,
      interviews, evaluation log and document analysis. Questionnaires and interviews
      were administered both before and after the evaluation: Pattern matching was used
      to analyze the data based on predetermined propositions. RESULTS: Individuals
      gained program knowledge that resulted in changes to both individual and program
      practices. One of the key themes was the importance clinicians placed on local,
      program based knowledge. The evaluation had less influence on the broader health
      organization. CONCLUSIONS: Program evaluation facilitated individual, team and
      organizational learning. The use of evaluation to support KT is ideally suited to
      a primary care setting by offering relevant and applicable knowledge to primary
      care team members while being sensitive to local context.

PMID- 27716159
TI  - The clinical and cost effectiveness of steroid injection compared with night
      splints for carpal tunnel syndrome: the INSTINCTS randomised clinical trial study
      protocol.
AB  - BACKGROUND: Patients diagnosed with idiopathic mild to moderate carpal tunnel
      syndrome (CTS) are usually managed in primary care and commonly treated with
      night splints and/or corticosteroid injection. The comparative effectiveness of
      these interventions has not been reliably established nor investigated in the
      medium and long term. The primary objective of this trial is to investigate
      whether corticosteroid injection is effective in reducing symptoms and improving
      hand function in mild to moderate CTS over 6 weeks when compared with night
      splints. Secondary objectives are to determine specified comparative clinical
      outcomes and cost effectiveness of corticosteroid injection over 6 and 24 months.
      METHOD/DESIGN: A multicentre, randomised, parallel group, clinical pragmatic
      trial will recruit 240 adults aged >=18 years with mild to moderate CTS from GP
      Practices and Primary-Secondary Care Musculoskeletal Interface Clinics. Diagnosis
      will be by standardised clinical assessment. Participants will be randomised on
      an equal basis to receive either one injection of 20 mg Depo-Medrone or a night
      splint to be worn for 6 weeks. The primary outcome is the overall score of the
      Boston Carpal Tunnel Questionnaire (BCTQ) at 6 weeks. Secondary outcomes are the
      BCTQ symptom severity and function status subscales, symptom intensity,
      interrupted sleep, adherence to splinting, perceived benefit and satisfaction
      with treatment, work absence and reduction in work performance, EQ-5D-5L,
      referral to surgery and health utilisation costs. Participants will be assessed
      at baseline and followed up at 6 weeks, 6, 12 and 24 months. The primary analysis
      will use an intention to treat (ITT) approach and multiple imputation for missing
      data. The sample size was calculated to detect a 15 % greater improvement in the
      BTCQ overall score in the injection group compared to night-splinting at
      approximately 90 % power, 5 % two-tailed significance and allows for 15 % loss to
      follow-up. DISCUSSION: The trial makes an important contribution to the evidence
      base available to support effective conservative management of CTS in primary
      care. No previous trials have directly compared these treatments for CTS in
      primary care populations, reported on clinical effectiveness at more than 6
      months nor compared cost effectiveness of the interventions. TRIAL REGISTRATION:
      Trial registration: EudraCT 2013-001435-48 (registered 05/06/2013),
      ClinicalTrials.gov NCT02038452 (registered 16/1/2014), and Current Controlled
      Trials ISRCTN09392969 (retrospectively registered 01/05/2014).

PMID- 27716162
TI  - Effectiveness of enhanced cognitive behavioral therapy (CBT-E) in the treatment
      of anorexia nervosa: a prospective multidisciplinary study.
AB  - BACKGROUND: Anorexia nervosa (AN) is a debilitating psychiatric disorder
      associated with a wide array of negative health complications and psychiatric
      comorbidity. Existing evidence for AN treatment in adults is weak, and no
      empirically supported treatment has been reliably established. The primary
      objective of this study is to gain knowledge about the effectiveness of enhanced
      cognitive behavioral therapy (CBT-E) for anorexia nervosa delivered in a public
      hospital setting. Baseline predictors of treatment outcome and dropout are
      studied. Furthermore, there will be collected blood and stool samples for a
      general biobank to be able to initiate research on possible pathophysiological
      mechanisms underlying AN. METHODS: The study will assess the potency of
      outpatient CBT-E in a sample of patients suffering from AN (age >16) admitted to
      the Section for Eating Disorders at the Department for Psychosomatic Medicine,
      Haukeland University Hospital in Bergen, Norway. The study has a longitudinal
      design with five main assessment time points: before treatment, at 3 months, at
      the end of treatment, at 20 weeks, and at 12 months follow-up including biobank
      samples. A control group without an eating disorder will also be recruited.
      DISCUSSION: Treatment research in a public hospital setting is important for
      gaining knowledge about the transportability of treatments evaluated in research
      clinics into ordinary clinical practice. Furthermore, biological material from
      the thoroughly described patient cohort will serve as a basis for further
      research on the pathophysiological mechanisms in AN. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02745067 . Registered 14 April 2016.  .

PMID- 27716163
TI  - The expression of 11beta-hydroxysteroid dehydrogenase type 1 is increased in
      experimental periodontitis in rats.
AB  - BACKGROUND: The involvement of 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1), which converts inactive glucocorticoids into active glucocorticoids
      intracellularly, in metabolic diseases and chronic inflammatory diseases has been
      elucidated. We recently reported that an increase in 11beta-HSD1 expression was
      associated with chronic periodontitis in humans irrespective of obesity. To
      further clarify the role of 11beta-HSD1 in chronic periodontitis, the expression
      of 11beta-HSD1 was investigated in experimental periodontitis model in rats.
      METHODS: Experimental periodontitis was induced by silk ligature of left
      maxillary second molars of 7-week-old male Wistar rats, and periodontal tissues
      were collected at day 3. The expression of 11beta-HSD1, 11beta-HSD2, and TNFalpha
      mRNA was examined using real time reverse transcription-polymerase chain
      reaction. The expression of TNFalpha was used as an indicator of inflammation.
      Thus, the rats in which the levels of TNFalpha mRNA were increased in the
      ligature-induced periodontitis compared with the control were analysed. RESULTS:
      The findings demonstrated that the expression of 11beta-HSD1 mRNA was
      significantly increased in experimental periodontitis compared with the control.
      The increase in the levels of 11beta-HSD1 mRNA in the ligature-induced
      periodontitis compared with the control was positively correlated with that of
      TNFalpha mRNA. On the other hand, the expression of 11beta-HSD2 mRNA, which
      inactivates glucocorticoids, was slightly decreased in experimental
      periodontitis. Therefore, the ratio of 11beta-HSD1 versus 11beta-HSD2 mRNA was
      significantly higher in experimental periodontitis than in the control.
      CONCLUSIONS: These results suggest that the increased expression of 11beta-HSD1,
      which would result in the increased levels of intracellular glucocorticoids, may
      play a role in the pathophysiology of experimental periodontitis.

PMID- 27716164
TI  - Carbapenem-Resistant Klebsiella pneumoniae influences the outcome of early
      infections in liver transplant recipients.
AB  - BACKGROUND: Infections remain a leading cause of morbidity and mortality among
      liver transplant (LT) recipients. The aim of our study was to define the factors
      associated with outcome of early bacterial and fungal infections in a cohort of
      patients who underwent LT at the University Hospital of Ancona over a nine year
      period. METHODS: All consecutive patients who underwent LT in our center were
      considered. An early infection was defined as occurring in the first month post
      transplantation. RESULTS: Among 330 patients who underwent LT from August 2005 to
      October 2014, 88 (27 %) had at least one infection documented within 30 days
      after transplantation. In 54 cases only one site was involved, in 34 cases >=2
      sites. There were 43 (30 %) pneumonia, 40 (27 %) surgical site infections, 31 (22
      %) blood stream infections, and 30 (21 %) urinary tract infections. Gram-negative
      bacteria accounted for 64 % of the culture-positive cases, followed by Gram
      positive bacteria (30 %) and fungi (6 %). A high proportion of drug-resistant
      strains was found within either Gram-negative (79 %) or Gram-positive (81 %)
      bacteria. There were 27 out 88 patients (31 %) who died within 180 days from the
      transplant. Factors independently associated with a higher risk of mortality
      were: renal replacement therapy (HR 11.797 [CI95 % 3.082-45.152], p < 0.0001),
      multisite infections (HR 4.865 [CI95 % 1.417-16.700], p = 0.012) and being
      infected with carbapenem-resistant Klebsiella pneumoniae (CRKP; HR 5.562 [CI95 %
      1.186-26.088], p = 0.030). CONCLUSIONS: Overall, these data indicate that early
      infections in LT patients are characterized by significant mortality. In
      particular, an early infection caused by CRKP has an adverse impact on survival
      in these patients suggesting an urgent need for adopting preventive measures to
      avoiding this complication.

PMID- 27716166
TI  - Selection into medical school: from tools to domains.
AB  - BACKGROUND: Most research into the validity of admissions tools focuses on the
      isolated correlations of individual tools with later outcomes. Instead, looking
      at how domains of attributes, rather than tools, predict later success is likely
      to be more generalizable. We aim to produce a blueprint for an admissions scheme
      that is broadly relevant across institutions. METHODS: We broke down all measures
      used for admissions at one medical school into the smallest possible component
      scores. We grouped these into domains on the basis of a multicollinearity
      analysis, and conducted a regression analysis to determine the independent
      validity of each domain to predict outcomes of interest. RESULTS: We identified
      four broad domains: logical reasoning and problem solving, understanding people,
      communication skills, and biomedical science. Each was independently and
      significantly associated with performance in final medical school examinations.
      CONCLUSIONS: We identified two potential errors in the design of admissions
      schema that can undermine their validity: focusing on tools rather than outcomes,
      and including a wide range of measures without objectively evaluating the
      independent contribution of each. Both could be avoided by following a process of
      programmatic assessment for selection.

PMID- 27716165
TI  - A randomized prospective controlled trial comparing the laryngeal tube suction
      disposable and the supreme laryngeal mask airway: the influence of head and neck
      position on oropharyngeal seal pressure.
AB  - BACKGROUND: The Laryngeal Tube Suction Disposable (LTS-D) and the Supreme
      Laryngeal Mask Airway (SLMA) are second generation supraglottic airway devices
      (SADs) with an added channel to allow gastric drainage. We studied the efficacy
      of these devices when using pressure controlled mechanical ventilation during
      general anesthesia for short and medium duration surgical procedures and compared
      the oropharyngeal seal pressure in different head and-neck positions. METHODS:
      Eighty patients in each group had either LTS-D or SLMA for airway management. The
      patients were recruited in two different institutions. Primary outcome variables
      were the oropharyngeal seal pressures in neutral, flexion, extension, right and
      left head-neck position. Secondary outcome variables were time to achieve an
      effective airway, ease of insertion, number of attempts, maneuvers necessary
      during insertion, ventilatory parameters, success of gastric tube insertion and
      incidence of complications. RESULTS: The oropharyngeal seal pressure achieved
      with the LTS-D was higher than the SLMA in, (extension (p=0.0150) and right
      position (p=0.0268   at 60 cm H2O intracuff pressures and nearly significant in
      neutral position (p = 0.0571). The oropharyngeal seal pressure was significantly
      higher with the LTS-D during neck extension as compared to SLMA (p= 0.015).
      Similar oropharyngeal seal pressures were detected in all other positions with
      each device. The secondary outcomes were comparable between both groups. Patients
      ventilated with LTS-D had higher incidence of sore throat (p = 0.527). No major
      complications occurred. CONCLUSIONS: Better oropharyngeal seal pressure was
      achieved with the LTS-D in head-neck right and extension positions , although it
      did not appear to have significance in alteration of management using pressure
      control mechanical ventilation in neutral position. The fiberoptic view was
      better with the SLMA. The post-operative sore throat incidence was higher in the
      LTS-D. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02856672 , Unique Protocol
      ID:BnaiZionMC-16-LG-001, Registered: August 2016.

PMID- 27716167
TI  - Prevalence of oral manifestations in children and adolescents with cancer
      submitted to chemotherapy.
AB  - BACKGROUND: Oral complications may be observed during chemotherapy and are
      important side effects that may directly affect the anticancer treatment, even
      causing septicaemia in some cases. This research was done in order to evaluate
      changes in oral lesions during follow-up of children and adolescents in
      chemotherapy at Hospital Estadual Infantil Nossa Senhora da Gloria (HEINSG).
      METHODS: The study design was longitudinal, 45 patients were evaluated and
      monitored for 1 month after the initiation of chemotherapy. Twenty-eight patients
      were male and 17 female, ranging from 3 months to 18 years old. RESULTS: The
      results show an increase in the number of mucositis cases and a decrease in
      xerostomia cases after the initiation of treatment, and other oral lesions were
      also found in low numbers. CONCLUSIONS: It is possible to avoid oral
      complications by maintaining a good oral health, and reducing infectious
      outbreaks. It is also feasible to obtain an early diagnosis of, and treat these
      oral complications, preventing them from following a more severe clinical course
      that may negatively affect the individual's treatment. This outcome requires the
      presence of a dental surgeon on the multidisciplinary cancer treatment team.

PMID- 27716168
TI  - A protocol of a randomized controlled multicenter trial for surgical treatment of
      lumbar spondylolisthesis: the Lumbar Interbody Fusion Trial (LIFT).
AB  - BACKGROUND: With a steep increase in the number of instrumented spinal fusion
      procedures, there is a need for comparative data to develop evidence based
      treatment recommendations. Currently, the available data on cost and clinical
      effectiveness of the two most frequently performed surgeries for lumbar
      spondylolisthesis, transforaminal lumbar interbody fusion (TLIF) and posterior
      lumbar interbody fusion (PLIF), are not sufficient. Therefore, current guidelines
      do not advise which is the most appropriate surgical treatment strategy for these
      patients. Non-randomized studies comparing TLIF and PLIF moreover suggest that
      TLIF is associated with fewer complications, less blood loss, shorter surgical
      time and hospital duration. TLIF may therefore be more cost-effective. The
      results of this study will provide knowledge on short- and long-term clinical and
      economical effects of TLIF and PLIF procedures, which will lead to
      recommendations for treating patients with lumbar spondylolisthesis. METHODS:
      Multicenter blinded Randomized Controlled Trial (RCT; blinding for the patient
      and statistician, not for the clinician and researcher). A total of 144 patients
      over 18 years old with symptomatic single level lumbar degenerative, isthmic or
      iatrogenic spondylolisthesis whom are candidates for LIF (lumbar interbody
      fusion) surgery through a posterior approach will be randomly allocated to TLIF
      or PLIF. The study will consist of three parts: 1) a clinical effectiveness
      study, 2) a cost-effectiveness study, and 3) a process evaluation. The primary
      clinical outcome measures are: change in disability measured with Oswestry
      Disability Index (ODI) and change in quality adjusted life years (QALY) measured
      with EQ-5D-5L. Secondary clinical outcome measures are: Short Form (36) Health
      Survey (SF-36), VAS back pain, VAS leg pain, Hospital Anxiety Depression Scale
      (HADS), complications, productivity related costs (iPCQ) and medical costs
      (iMCQ). Measurements will be carried out at five fixed time points (pre
      operatively and at 3, 6, 12 and 24 months). DISCUSSION: It is hypothesized that
      TLIF, compared to PLIF, has similar clinical outcome or is possibly better in
      reducing disability. Moreover, direct medical costs are expected to be lower due
      to less surgical morbidity, shorter hospital stay and shorter surgical time.
      Indirect costs are assumed to be lower for TLIF as well, because we suspect less
      working days are lost. Currently, prospective data comparing clinical and cost
      effectiveness of both techniques are not available. Therefore, in clinical
      practice both techniques are used and the choice for technique is greatly based
      on surgeon's preference. The demand for spinal fusion surgery has risen steeply
      over the last 10 years and is expected to increase even further in the near
      future. As a result, the burden on society (and the working population) will
      increase. In case our hypothesis is confirmed, treatment guidelines will be
      adapted, and TLIF will be recommended as first choice surgical treatment of
      lumbar spondylolisthesis. Ultimately this will lead to reduction of (direct and
      indirect) costs and better clinical outcome for spondylolisthesis patients
      eligible for instrumented spinal surgery. TRIAL REGISTRATION NUMBER: Netherlands
      Trial Registry, number 5722 (registration date March 30, 2016).

PMID- 27716169
TI  - Viscoelastic properties of human and bovine articular cartilage: a comparison of
      frequency-dependent trends.
AB  - BACKGROUND: The purpose of this study was to compare the frequency-dependent
      viscoelastic properties of human and bovine cartilage. METHODS: Full-depth
      cartilage specimens were extracted from bovine and human femoral heads. Using
      dynamic mechanical analysis, the viscoelastic properties of eight bovine and six
      human specimens were measured over the frequency range 1 Hz to 88 Hz. Significant
      differences between bovine and human cartilage viscoelastic properties were
      assessed using a Mann-Whitney test (p < 0.05). RESULTS: Throughout the range of
      frequencies tested and for both species, the storage modulus was greater than the
      loss modulus and both were frequency-dependent. The storage and loss moduli of
      all human and bovine cartilage specimens presented a logarithmic relationship
      with respect to frequency. The mean human storage modulus ranged from 31.9 MPa to
      43.3 MPa, while the mean bovine storage modulus ranged from 54.0 MPa to 80.5 MPa;
      bovine storage moduli were 1.7 to 1.9 times greater than the human modulus.
      Similarly, the loss modulus of bovine cartilage was 2.0 to 2.1 times greater than
      human. The mean human loss modulus ranged from 5.3 MPa to 8.5 MPa while bovine
      moduli ranged from 10.6 MPa to 18.1 MPa. CONCLUSION: Frequency-dependent
      viscoelastic trends of bovine articular cartilage were consistent with those of
      human articular cartilage; this includes a similar frequency dependency and high
      frequency plateau. Bovine cartilage was, however, 'stiffer' than human by a
      factor of approximately 2. With these provisos, bovine articular cartilage may be
      a suitable dynamic model for human articular cartilage.

PMID- 27716170
TI  - Impact of mass-screening on tuberculosis incidence in a prospective cohort of
      Brazilian prisoners.
AB  - BACKGROUND: Globally, prison inmates are a high-risk population for tuberculosis
      (TB), but the specific drivers of disease and impact of mass screening
      interventions are poorly understood. METHODS: We performed a prospective cohort
      study to characterize the incidence and risk factors for tuberculosis infection
      and disease in 12 Brazilian prisons, and to investigate the effect of mass
      screening on subsequent disease risk. After recruiting a stratified random sample
      of inmates, we administered a questionnaire to ascertain symptoms and potential
      risk factors for tuberculosis; performed tuberculin skin testing (TST); collected
      sera for HIV testing; and obtained two sputum samples for smear microscopy and
      culture, from participants reporting a cough of any duration. We repeated the
      questionnaire and all tests for inmates who remained incarcerated after 1 year.
      TST conversion was defined as TST >=10 mm and an induration increase of at least
      6 mm in an individual with a baseline TST <10 mm. Cox proportional hazard models
      were performed to identify risk factors associated with active TB. To evaluate
      the impact of screening on subsequent risk of disease, we compared TB
      notifications over one year among individuals randomized to screening for active
      TB with those not randomized to screening. RESULTS: Among 3,771 inmates
      recruited, 3,380 (89.6 %) were enrolled in the study, and 1,422 remained
      incarcerated after one year. Among 1,350 inmates (94.9 %) with paired TSTs at
      baseline and one-year follow-up, 25.7 % (272/1060) converted to positive. Among
      those incarcerated for the year, 10 (0.7 %) had TB at baseline and 25 (1.8 %)
      were diagnosed with TB over the subsequent year. Cases identified through active
      screening were less likely to be smear-positive than passively detected cases
      (10.0 % vs 50.9 %; p < 0.01), suggesting early case detection. However, there was
      no reduction in subsequent disease among individuals actively screened versus
      those not screened (1.3 % vs 1.7 %; p = 0.88). Drug use during the year (AHR
      3.22; 95 % CI 1.05-9.89) and knows somebody with TB were (AHR 2.86; 95 % CI 1.01
      8.10) associated with active TB during one year of follow up CONCLUSIONS: Mass
      screening in twelve Brazilian prisons did not reduce risk of subsequent disease
      in twelve Brazilian prisons, likely due to an extremely high force of infection.
      New approaches are needed to control TB in this high-transmission setting.

PMID- 27716171
TI  - Coffee and caffeine intake and risk of urinary incontinence: a meta-analysis of
      observational studies.
AB  - BACKGROUND: Previous results from studies on the relationship between
      coffee/caffeine consumption and risk of urinary incontinence (UI) are
      inconclusive. We aim to assess this association using a meta-analysis of
      observational studies. METHODS: Pertinent studies were identified by searching
      electronic database (Embase, PubMed and Web of Science) and carefully reviewing
      the reference lists of pertinent articles until July 2015. Random-effects models
      were used to derive the summary ORs and corresponding 95 % CIs. RESULTS: Seven
      studies (one case-control, two cohort and four cross-sectional) were included in
      our meta-analysis. The summary ORs for any versus non-consumption were 0.75 (95 %
      CI 0.54-1.04) for coffee and 1.29 (95 % CI 0.94-1.76) for caffeine consumption.
      Compared with individuals who never drink coffee, the pooled OR of UI was 0.99
      (95 % CI 0.83-1.18) for regular coffee/caffeine drinkers. Coffee/caffeine
      consumption was not associated with moderate to severe UI (OR 1.18, 95 % CI 0.88
      1.58). In stratified analyses by gender, no significant association was found
      between UI risk and coffee/caffeine consumption in both men (OR 0.99, 95 % CI
      0.42-2.32) and women (OR 0.92, 95 % CI 0.80-1.06). By subtype, the pooled ORs
      were 1.01 (95 % CI 0.86-1.19) for stress UI, 0.99 (95 % CI 0.84-1.16) for urge UI
      and 0.93 (95 % CI 0.79-1.10) for mixed UI. CONCLUSIONS: This meta-analysis found
      no evidence for an association between coffee/caffeine consumption and the risk
      of UI.

PMID- 27716173
TI  - Erratum to: 'Early prediction of acute kidney injury after transapical and
      transaortic aortic valve implantation with urinary G1 cell cycle arrest
      biomarkers'.

PMID- 27716172
TI  - Treatment of plaque psoriasis with an ointment formulation of the Janus kinase
      inhibitor, tofacitinib: a Phase 2b randomized clinical trial.
AB  - BACKGROUND: Most psoriasis patients have mild to moderate disease, commonly
      treated topically. Current topical agents have limited efficacy and undesirable
      side effects associated with long-term use. Tofacitinib is a small molecule Janus
      kinase inhibitor investigated for the topical treatment of psoriasis. METHODS:
      This was a 12-week, randomized, double-blind, parallel-group, vehicle-controlled
      Phase 2b study of tofacitinib ointment (2 % and 1 %) applied once (QD) or twice
      (BID) daily in adults with mild to moderate plaque psoriasis. Primary endpoint:
      proportion of patients with Calculated Physician's Global Assessment (PGA-C)
      clear or almost clear and >=2 grade improvement from baseline at Weeks 8 and 12.
      Secondary endpoints: proportion of patients with PGA-C clear or almost clear;
      proportion achieving Psoriasis Area and Severity Index 75 (PASI75) response;
      percent change from baseline in PASI and body surface area; change from baseline
      in Itch Severity Item (ISI). Adverse events (AEs) were monitored and clinical
      laboratory parameters measured. RESULTS: Overall, 435 patients were randomized
      and 430 patients received treatment. The proportion of patients with PGA-C clear
      or almost clear and >=2 grade improvement from baseline at Week 8 was 18.6 % for
      2 % tofacitinib QD (80 % confidence interval [CI] for difference from vehicle:
      3.8, 18.2 %) and 22.5 % for 2 % tofacitinib BID (80 % CI: 3.1, 18.5 %); this was
      significantly higher vs vehicle for both dosage regimens. No significant
      difference vs vehicle was seen at Week 12. Significantly more patients achieved
      PGA-C clear or almost clear with 2 % tofacitinib QD and BID and 1 % tofacitinib
      QD (not BID) at Week 8, and with 2 % tofacitinib BID at Week 12. Pruritus was
      significantly reduced vs vehicle with 2 % and 1 % tofacitinib BID (starting Day
      2), and 2 % tofacitinib QD (starting Day 3). Overall, 44.2 % of patients
      experienced AEs, 8.1 % experienced application site AEs, and 2.3 % experienced
      serious AEs. The highest incidence of AEs (including application site AEs) was in
      the vehicle QD group. CONCLUSIONS: In adults with mild to moderate plaque
      psoriasis, 2 % tofacitinib ointment QD and BID showed greater efficacy than
      vehicle at Week 8, but not Week 12, with an acceptable safety and local
      tolerability profile. TRIAL REGISTRATION: NCT01831466 registered March 28, 2013.

PMID- 27716174
TI  - Erratum to: Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
      associated with lateral medullary syndrome: case report and literature review.

PMID- 27716175
TI  - Relationship between Massachusetts Youth Screening Instrument-second version and
      psychiatric disorders in youths in welfare and juvenile justice institutions in
      Switzerland.
AB  - BACKGROUND: There is growing evidence that it is important to have well
      standardized procedures for identifying the mental health needs of youths in
      welfare and juvenile justice institutions. One of the most widely used tools for
      mental health screening in the juvenile justice system is the Massachusetts Youth
      Screening Instrument-second version (MAYSI-2). To contribute to the body of
      research examining the utility of the MAYSI-2 as a mental health screening tool;
      the first objective of the current study was to examine the relationship between
      the MAYSI-2 and the Schedule for Affective Disorders and Schizophrenia for School
      Age Children, Present and Lifetime version (K-SADS-PL) in a sample of Swiss
      youths in welfare and juvenile justice institutions using a cross-sectional
      design. Secondly, as the sample was drawn from the French-, German- and Italian
      speaking parts of Switzerland, the three languages were represented in the total
      sample and consequently differences between the language regions were analyzed as
      well. The third objective was to examine gender differences in this relationship.
      METHODS: Participants were 297 boys and 149 girls (mean age = 16.2, SD = 2.5)
      recruited from 64 youth welfare and juvenile justice institutions in Switzerland.
      The MAYSI-2 was used to screen for mental health or behavioral problems that
      could require further evaluation. Psychiatric classification was based on the
      Schedule for Affective Disorders and Schizophrenia for School-Age Children,
      Present and Lifetime version (K-SADS-PL). Binomial logistic regression analysis
      was used to predict (cluster of) psychiatric disorders from MAYSI-2 scales.
      RESULTS: The regression analyses revealed that the MAYSI-2 scales generally
      related well to their corresponding homotypic (cluster of) psychiatric disorders.
      For example, the alcohol/drug use scale identified the presence of any substance
      use disorder and the suicide ideation scale identified youths reporting suicide
      ideation or suicide attempts. Several MAYSI-2 scales were also related to
      heterotypic (cluster of) psychiatric disorders. For example, the MAYSI-2 scale
      alcohol/drug use, was positively related to any disruptive disorder. Furthermore,
      the results revealed gender differences in the relationship between the MAYSI-2
      and K-SADS-PL (e.g., in the boys' subsample no MAYSI-2 scale was significantly
      related to any affective disorder; whereas, in the girls' subsample the MAYSI-2
      scales depressed-anxious and somatic complaints were significantly related to any
      affective disorder). CONCLUSIONS: Overall, The MAYSI-2 seems to serve well as a
      first-stage screen to identify service needs for youths in welfare and juvenile
      justice institutions in Switzerland. Its effectiveness to identify the presence
      of (cluster of) psychiatric disorders differs between genders.

PMID- 27716176
TI  - Relation between BCG vaccine scar and an interferon-gamma release assay in
      immigrant children with "positive" tuberculin skin test (>=10 mm).
AB  - BACKGROUND: Immigrants from countries with high incidence of tuberculosis (TB)
      are usually offered screening when they arrive to low incidence countries. The
      tuberculin skin test (TST) is often used. The interferon gamma release assays
      (IGRAs) are more specific and not affected by BCG vaccination. The aims of this
      study were 1. To see if there if there is a correlation between a positive IGRA
      (QFT) and presence of a BCG scar in children with TST >=10 mm, 2. To compare the
      TST diameter with QFT result, 3. To see if chest X-ray can be omitted in QFT
      negative children despite TST >=10 mm. METHODS: 762 healthy children/adolescents
      (median age 14 years) arriving to Gothenburg and surroundings with TST >=10 mm
      were tested with QFT. RESULTS: A total of 163/492 (33 %) children with BCG scar
      had positive QFT, whereas 205/270 (76 %) without BCG scar had positive QFT (p <
      0.0001). The median TST was 12 mm in QFT negative and 18 mm in QFT positive
      children (p < 0.0001) but with considerable overlap. Median TST was the same (12
      mm) in QFT negative children with and without BCG scar. Among the QFT positive
      children 25/368 had chest X-ray changes compared to 2/393 among the QFT negative
      children (p < 0.0007). CONCLUSIONS: Previous BCG vaccination had an effect on the
      TST diameter so an IGRA is recommended to diagnose latent TB. Using only TST for
      screening of latent TB would lead to overdiagnosis. The TST diameter was larger
      in QFT positive than in QFT negative children but could not predict QFT in the
      individual patient. Chest X ray contributes little to the diagnosis of TB in QFT
      negative children but can not be omitted because of late seroconversion of QFT in
      some patients. TRIAL REGISTRATION: Not applicable.

PMID- 27716178
TI  - Securizing data linkage in french public statistics.
AB  - Administrative records in France, especially medical and social records, have
      huge potential for statistical studies. The NIR (a national identifier) is widely
      used in medico-social administrations, and this would theoretically provide
      considerable scope for data matching, on condition that the legislation on such
      matters was respected.The law, however, forbids the processing of non-anonymized
      medical data, thus making it difficult to carry out studies that require several
      sources of social and medical data.We would like to benefit from computer
      techniques introduced since the 70 s to provide safe linkage of anonymized files,
      to release the current constraints of such procedures.We propose an organization
      and a data workflow, based on hashing and cyrptographic techniques, to strongly
      compartmentalize identifying and not-identifying data.The proposed method offers
      a strong control over who is in possession of which information, using different
      hashing keys for each linkage. This allows to prevent unauthorized linkage of
      data, to protect anonymity, by preventing cumulation of not-identifying data
      which can become identifying data when linked.Our proposal would make it possible
      to conduct such studies more easily, more regularly and more precisely while
      preserving a high enough level of anonymity.The main obstacle to setting up such
      a system, in our opinion, is not technical, but rather organizational in that it
      is based on the existence of a Key-Management Authority.

PMID- 27716177
TI  - Using a complex adaptive system lens to understand family caregiving experiences
      navigating the stroke rehabilitation system.
AB  - BACKGROUND: Family caregivers provide the stroke survivor with social support and
      continuity during the transition home from a rehabilitation facility. In this
      exploratory study we examined family caregivers' perceptions and experiences
      navigating the stroke rehabilitation system. The theories of continuity of care
      and complex adaptive systems were integrated to examine the transition from a
      stroke rehabilitation facility to the patient's home. This study provides an
      understanding of the interacting complexities at the macro and micro levels.
      METHODS: A convenient sample of family caregivers (n = 14) who provide care for a
      stroke survivor were recruited 4-12 weeks following the patient's discharge from
      a stroke rehabilitation facility in Ontario, Canada. Interviews were conducted
      with family caregivers to examine their perceptions and experiences navigating
      the stroke rehabilitation system. Directed and inductive content analysis and the
      theory of Complex Adaptive Systems were used to interpret the perceptions of
      family caregivers. RESULTS: Health system policies and procedures at the macro
      level determined the types and timing of information being provided to
      caregivers, and impacted continuity of care and access to supports and services
      at the micro-level. Supports and services in the community, such as outpatient
      physiotherapy services, were limited or did not meet the specific needs of the
      stroke survivors or family caregivers. CONCLUSION: Relationships with health
      providers, informational support, and continuity in case management all influence
      the family caregiving experience and ultimately the quality of care for the
      stroke survivor, during the transition home from a rehabilitation facility.

PMID- 27716179
TI  - A knowledge translation intervention to enhance clinical application of a virtual
      reality system in stroke rehabilitation.
AB  - BACKGROUND: Despite increasing evidence for the effectiveness of virtual reality
      (VR)-based therapy in stroke rehabilitation, few knowledge translation (KT)
      resources exist to support clinical integration. KT interventions addressing
      known barriers and facilitators to VR use are required. When environmental
      barriers to VR integration are less amenable to change, KT interventions can
      target modifiable barriers related to therapist knowledge and skills. METHODS: A
      multi-faceted KT intervention was designed and implemented to support physical
      and occupational therapists in two stroke rehabilitation units in acquiring
      proficiency with use of the Interactive Exercise Rehabilitation System (IREX;
      GestureTek). The KT intervention consisted of interactive e-learning modules,
      hands-on workshops and experiential practice. Evaluation included the Assessing
      Determinants of Prospective Take Up of Virtual Reality (ADOPT-VR) Instrument and
      self-report confidence ratings of knowledge and skills pre- and post-study.
      Usability of the IREX was measured with the System Usability Scale (SUS). A focus
      group gathered therapist experiences. Frequency of IREX use was recorded for 6
      months post-study. RESULTS: Eleven therapists delivered a total of 107 sessions
      of VR-based therapy to 34 clients with stroke. On the ADOPT-VR, significant pre
      post improvements in therapist perceived behavioral control (p = 0.003), self
      efficacy (p = 0.005) and facilitating conditions (p =0.019) related to VR use
      were observed. Therapist intention to use VR did not change. Knowledge and skills
      improved significantly following e-learning completion (p = 0.001) and was
      sustained 6 months post-study. Below average perceived usability of the IREX
      (19th percentile) was reported. Lack of time was the most frequently reported
      barrier to VR use. A decrease in frequency of perceived barriers to VR use was
      not significant (p = 0.159). Two therapists used the IREX sparingly in the 6
      months following the study. Therapists reported that client motivation to engage
      with VR facilitated IREX use in practice but that environmental and IREX-specific
      barriers limited use. CONCLUSIONS: Despite increased knowledge and skills in VR
      use, the KT intervention did not alter the number of perceived barriers to VR
      use, intention to use or actual use of VR. Poor perceived system usability had an
      impact on integration of this particular VR system into clinical practice.

PMID- 27716180
TI  - Generation of an integrated Hieracium genomic and transcriptomic resource enables
      exploration of small RNA pathways during apomixis initiation.
AB  - BACKGROUND: Application of apomixis, or asexual seed formation, in crop breeding
      would allow rapid fixation of complex traits, economizing improved crop delivery.
      Identification of apomixis genes is confounded by the polyploid nature, high
      genome complexity and lack of genomic sequence integration with reproductive
      tissue transcriptomes in most apomicts. RESULTS: A genomic and transcriptomic
      resource was developed for Hieracium subgenus Pilosella (Asteraceae) which
      incorporates characterized sexual, apomictic and mutant apomict plants exhibiting
      reversion to sexual reproduction. Apomicts develop additional female gametogenic
      cells that suppress the sexual pathway in ovules. Disrupting small RNA pathways
      in sexual Arabidopsis also induces extra female gametogenic cells; therefore, the
      resource was used to examine if changes in small RNA pathways correlate with
      apomixis initiation. An initial characterization of small RNA pathway genes
      within Hieracium was undertaken, and ovary-expressed ARGONAUTE genes were
      identified and cloned. Comparisons of whole ovary transcriptomes from mutant
      apomicts, relative to the parental apomict, revealed that differentially
      expressed genes were enriched for processes involved in small RNA biogenesis and
      chromatin silencing. Small RNA profiles within mutant ovaries did not reveal
      large-scale alterations in composition or length distributions; however, a small
      number of differentially expressed, putative small RNA targets were identified.
      CONCLUSIONS: The established Hieracium resource represents a substantial
      contribution towards the investigation of early sexual and apomictic female
      gamete development, and the generation of new candidate genes and markers.
      Observed changes in small RNA targets and biogenesis pathways within sexual and
      apomictic ovaries will underlie future functional research into apomixis
      initiation in Hieracium.

PMID- 27716181
TI  - Emergence of wheat blast in Bangladesh was caused by a South American lineage of
      Magnaporthe oryzae.
AB  - BACKGROUND: In February 2016, a new fungal disease was spotted in wheat fields
      across eight districts in Bangladesh. The epidemic spread to an estimated 15,000
      hectares, about 16 % of the cultivated wheat area in Bangladesh, with yield
      losses reaching up to 100 %. Within weeks of the onset of the epidemic, we
      performed transcriptome sequencing of symptomatic leaf samples collected directly
      from Bangladeshi fields. RESULTS: Reinoculation of seedlings with strains
      isolated from infected wheat grains showed wheat blast symptoms on leaves of
      wheat but not rice. Our phylogenomic and population genomic analyses revealed
      that the wheat blast outbreak in Bangladesh was most likely caused by a wheat
      infecting South American lineage of the blast fungus Magnaporthe oryzae.
      CONCLUSION: Our findings suggest that genomic surveillance can be rapidly applied
      to monitor plant disease outbreaks and provide valuable information regarding the
      identity and origin of the infectious agent.

PMID- 27716182
TI  - Self-perceived uselessness is associated with lower likelihood of successful
      aging among older adults in China.
AB  - BACKGROUND: Plenty of evidence has shown that self-perceived uselessness among
      older adults is negatively associated with successful aging in terms of good
      health in Western societies. It is unclear whether these findings are valid in
      China where living into older age is more selective due to high mortality at
      younger ages. METHODS: Using five waves (2000, 2002, 2005, 2008/2009 and
      2011/2012) of a large nationally representative survey in China with 29,954
      observations from 19,070 older adults aged 65 and older, this study aimed to
      investigate the association between self-perceived uselessness and successful
      aging. Self-perceived uselessness was measured by a single item "with age, do you
      feel more useless?" with six answers: always, often, sometimes, seldom, never,
      and unable to answer. Successful aging was measured by independence in activities
      of daily living (ADL), independence in instrumental activities of daily living
      (IADL), unimpaired cognition, good life satisfaction, and good self-rated health.
      Logistic regression models were applied to each successful aging indicator after
      controlling for a rich set of covariates that included demographics,
      socioeconomic status, family/social support, and health practices. The models
      also adjusted for intraperson correlations across waves. RESULTS: We found that
      self-perceived uselessness was negatively associated with successful aging among
      older adults aged 65 or older. Specifically, compared to never having self
      perceived uselessness, always having such a perception was associated with 16-42
      % lower odds of being ADL independent, IADL independent, cognitively unimpaired,
      and having good life satisfaction and good self-rated health. Often or sometimes
      having such a perception also reduced odds of aging successfully, although such
      reductions were less pronounced. The associations were similar among the oldest
      old aged 80 or older with one exception for the case of IADL independence.
      CONCLUSIONS: Self-perceived uselessness is negatively associated with successful
      aging among Chinese older adults as well as among the oldest-old. Our findings
      could be informative for China in the development of public health programs that
      aim to improve self-perceptions about aging and promote successful aging.

PMID- 27716183
TI  - Development of a video-based education and process change intervention to improve
      advance cardiopulmonary resuscitation decision-making.
AB  - BACKGROUND: Advance cardiopulmonary resuscitation (CPR) decision-making and
      escalation of care discussions are variable in routine clinical practice. We
      aimed to explore physician barriers to advance CPR decision-making in an
      inpatient hospital setting and develop a pragmatic intervention to support
      clinicians to undertake and document routine advance care planning discussions.
      METHODS: Two focus groups, which involved eight consultants and ten junior
      doctors, were conducted following a review of the current literature. A
      subsequent iterative consensus process developed two intervention elements: (i)
      an updated 'Goals of Patient Care' (GOPC) form and process; (ii) an education
      video and resources for teaching advance CPR decision-making and communication. A
      multidisciplinary group of health professionals and policy-makers with experience
      in systems development, education and research provided critical feedback.
      RESULTS: Three key themes emerged from the focus groups and the literature, which
      identified a structure for the intervention: (i) knowing what to say; (ii)
      knowing how to say it; (iii) wanting to say it. The themes informed the
      development of a video to provide education about advance CPR decision-making
      framework, improving communication and contextualising relevant clinical issues.
      Critical feedback assisted in refining the video and further guided development
      and evolution of a medical GOPC approach to discussing and recording medical
      treatment and advance care plans. CONCLUSION: Through an iterative process of
      consultation and review, video-based education and an expanded GOPC form and
      approach were developed to address physician and systemic barriers to advance CPR
      decision-making and documentation. Implementation and evaluation across hospital
      settings is required to examine utility and determine effect on quality of care.

PMID- 27716185
TI  - The influence of power and actor relations on priority setting and resource
      allocation practices at the hospital level in Kenya: a case study.
AB  - BACKGROUND: Priority setting and resource allocation in healthcare organizations
      often involves the balancing of competing interests and values in the context of
      hierarchical and politically complex settings with multiple interacting actor
      relationships. Despite this, few studies have examined the influence of actor and
      power dynamics on priority setting practices in healthcare organizations. This
      paper examines the influence of power relations among different actors on the
      implementation of priority setting and resource allocation processes in public
      hospitals in Kenya. METHODS: We used a qualitative case study approach to examine
      priority setting and resource allocation practices in two public hospitals in
      coastal Kenya. We collected data by a combination of in-depth interviews of
      national level policy makers, hospital managers, and frontline practitioners in
      the case study hospitals (n = 72), review of documents such as hospital plans and
      budgets, minutes of meetings and accounting records, and non-participant
      observations in case study hospitals over a period of 7 months. We applied a
      combination of two frameworks, Norman Long's actor interface analysis and
      VeneKlasen and Miller's expressions of power framework to examine and interpret
      our findings RESULTS: The interactions of actors in the case study hospitals
      resulted in socially constructed interfaces between: 1) senior managers and
      middle level managers 2) non-clinical managers and clinicians, and 3) hospital
      managers and the community. Power imbalances resulted in the exclusion of middle
      level managers (in one of the hospitals) and clinicians and the community (in
      both hospitals) from decision making processes. This resulted in, amongst others,
      perceptions of unfairness, and reduced motivation in hospital staff. It also puts
      to question the legitimacy of priority setting processes in these hospitals.
      CONCLUSIONS: Designing hospital decision making structures to strengthen
      participation and inclusion of relevant stakeholders could improve priority
      setting practices. This should however, be accompanied by measures to empower
      stakeholders to contribute to decision making. Strengthening soft leadership
      skills of hospital managers could also contribute to managing the power dynamics
      among actors in hospital priority setting processes.

PMID- 27716184
TI  - Amino-acid PET versus MRI guided re-irradiation in patients with recurrent
      glioblastoma multiforme (GLIAA) - protocol of a randomized phase II trial (NOA
      10/ARO 2013-1).
AB  - BACKGROUND: The higher specificity of amino-acid positron emission tomography (AA
      PET) in the diagnosis of gliomas, as well as in the differentiation between
      recurrence and treatment-related alterations, in comparison to contrast
      enhancement in T1-weighted MRI was demonstrated in many studies and is the
      rationale for their implementation into radiation oncology treatment planning.
      Several clinical trials have demonstrated the significant differences between AA
      PET and standard MRI concerning the definition of the gross tumor volume (GTV). A
      small single-center non-randomized prospective study in patients with recurrent
      high grade gliomas treated with stereotactic fractionated radiotherapy (SFRT)
      showed a significant improvement in survival when AA-PET was integrated in target
      volume delineation, in comparison to patients treated based on CT/MRI alone.
      METHODS: This protocol describes a prospective, open label, randomized, multi
      center phase II trial designed to test if radiotherapy target volume delineation
      based on FET-PET leads to improvement in progression free survival (PFS) in
      patients with recurrent glioblastoma (GBM) treated with re-irradiation, compared
      to target volume delineation based on T1Gd-MRI. The target sample size is 200
      randomized patients with a 1:1 allocation ratio to both arms. The primary
      endpoint (PFS) is determined by serial MRI scans, supplemented by AA-PET-scans
      and/or biopsy/surgery if suspicious of progression. Secondary endpoints include
      overall survival (OS), locally controlled survival (time to local progression or
      death), volumetric assessment of GTV delineated by either method, topography of
      progression in relation to MRI- or PET-derived target volumes, rate of long term
      survivors (>1 year), localization of necrosis after re-irradiation, quality of
      life (QoL) assessed by the EORTC QLQ-C15 PAL questionnaire, evaluation of safety
      of FET-application in AA-PET imaging and toxicity of re-irradiation. DISCUSSION:
      This is a protocol of a randomized phase II trial designed to test a new strategy
      of radiotherapy target volume delineation for improving the outcome of patients
      with recurrent GBM. Moreover, the trial will help to develop a standardized
      methodology for the integration of AA-PET and other imaging biomarkers in
      radiation treatment planning. TRIAL REGISTRATION: The GLIAA trial is registered
      with ClinicalTrials.gov ( NCT01252459 , registration date 02.12.2010), German
      Clinical Trials Registry ( DRKS00000634 , registration date 10.10.2014), and
      European Clinical Trials Database (EudraCT-No. 2012-001121-27, registration date
      27.02.2012).

PMID- 27716186
TI  - Quality of diabetes care and health insurance coverage: a retrospective study in
      an outpatient academic public hospital in Switzerland.
AB  - BACKGROUND: Socioeconomic disadvantage is associated with an increased risk of
      adverse diabetes outcomes. In Switzerland, a country with theoretical universal
      healthcare coverage, people without health insurance face barriers in accessing
      to and in receiving standard quality care. The Geneva University Hospitals (HUG)
      have implemented policies aiming at reducing these gaps. We compared quality of
      diabetes care and ambulatory healthcare services utilization among insured and
      uninsured diabetic patients. METHODS: This retrospective study linked health and
      administrative data of type 2 diabetic outpatients with at least one HbA1c test
      performed in 2012-2013 at HUG. Quality of care evaluation relied on processes
      (annual serum HbA1c, cholesterol and microalbuminuria tesing) and outcomes
      (HbA1c) assessment. Healthcare utilization was assessed by the number of
      ambulatory clinical and laboratory visits. Results were stratified by disease
      course (newly diagnosed versus prevalent diabetes). RESULTS: Of the 198 patients
      included, 80 (40.4 %) were uninsured. Both groups underwent annual testing of
      HbA1c, cholesterol, kidney function and microalbuminuria at comparably high rates
      and numbers of ambulatory visits did not significantly differ. After adjustments
      for age and sex, there were no significant differences in serum HbA1c between
      groups both in those with prevalent or with newly diagnosed diabetes. Initial
      medical intervention entailed comparable glycaemic improvement after 6 months in
      incident diabetes among insured and uninsured patients. CONCLUSIONS: This study
      did not find any difference in quality of diabetes care between insured and
      uninsured patients in a public hospital enforcing health-equity policies for
      access to and for delivery of standard diabetes care. It highlights the frontline
      role of public hospitals in contributing to care delivery equity even in
      countries with theoretical universal healthcare coverage.

PMID- 27716188
TI  - Circle of care modelling: an approach to assist in reasoning about healthcare
      change using a patient-centric system.
AB  - BACKGROUND: Many health system and health Information and Communication
      Technology (ICT) projects do not achieve their expected benefits. This paper
      presents an approach to exploring changes in the healthcare system to better
      understand the expected improvements and other changes by using a patient-centric
      modelling approach. Circle of care modeling (CCM) was designed to assist
      stakeholders in considering healthcare system changes using a patient centric
      approach. METHODS: The CCM approach is described. It includes four steps, based
      on soft systems methodology: finding out, conceptual modelling, structured
      discussion, and describing potential improvements. There are four visualizations
      that are used though this process: patient-persona based rich pictures of care
      flows (as part of finding out), and three models: provider view, communication
      view, and information repository view (as part of conceptual modelling). RESULTS:
      Three case studies are presented where CCM was applied to different real-world
      healthcare problems: 1. Seeking improvements in continuity of care for end of
      life patients. 2. Exploring current practices for medication communication for
      ambulatory patients prior to an update of a jurisdictional drug information
      system. 3. Deciding how to improve attachment of patients to primary care. The
      cases illustrate how CCM helped stakeholders reason from a patient centered
      approach about gaps and improvements in care such as: data fragmentation (in 1),
      coordination efforts of medication management (in 2), and deciding to support a
      community health centre for unattached patients (in 3). DISCUSSION: The circle of
      care modelling approach has proved to be a useful tool in assisting stakeholders
      explore health system change in a patient centric approach. It is one way to
      instantiate the important principle of being patient centered into practice when
      considering health system changes.

PMID- 27716187
TI  - A three perspective study of the sense of home of nursing home residents: the
      views of residents, care professionals and relatives.
AB  - BACKGROUND: The sense of home of nursing home residents is a multifactorial
      phenomenon which is important for the quality of living. This purpose of this
      study is to investigate the factors influencing the sense of home of older adults
      residing in the nursing home from the perspective of residents, relatives and
      care professionals. METHODS: A total of 78 participants (n = 24 residents, n = 18
      relatives and n = 26 care professionals) from 4 nursing homes in the Netherlands
      engaged in a qualitative study, in which photography was as a supportive tool for
      subsequent interviews and focus groups. The data were analyzed based on open
      ended coding, axial coding and selective coding. RESULTS: The sense of home of
      nursing home residents is influenced by a number of jointly identified factors,
      including the building and interior design; eating and drinking; autonomy and
      control; involvement of relatives; engagement with others and activities; quality
      of care are shared themes. Residents and relatives stressed the importance of
      having a connection with nature and the outdoors, as well as coping strategies.
      Relatives and care professionals emphasized the role the organization of
      facilitation of care played, as well as making residents feel like they still
      matter. CONCLUSIONS: The sense of home of nursing home residents is influenced by
      a multitude of factors related to the psychology of the residents, and the social
      and built environmental contexts. A holistic understanding of which factors
      influence the sense of home of residents can lead to strategies to optimize this
      sense of home. This study also indicated that the nursing home has a dual nature
      as a place of residence and a place where people are supported through numerous
      care strategies.

PMID- 27716189
TI  - Awareness and implementation of nine World Health Organization's patient safety
      solutions among three groups of healthcare workers in Oman.
AB  - BACKGROUND: The pressing need to reduce burgeoning poor safety measures affecting
      millions worldwide has alerted World Health Assembly to set-up mechanisms to
      increase patient safety. In response to such needs, World Health Organization
      (WHO) formulated nine life-saving patient safety solutions that would be
      essential to lower reduce healthcare-related harm. There is a paucity of research
      examining awareness of such nine patient safety solutions. This study has been
      designed and conducted to compare self-estimated awareness and practice of the
      World Health Organization's nine "Life-saving Patient Safety Solutions" aide
      memoirs among different groups of healthcare workers in Oman. METHODS: All
      nationwide healthcare workers (nurses, physicians and allied health
      professionals) in hospitals and primary healthcare under the auspice of Ministry
      of Health were the target population of this survey. Participants were selected
      by a simple, systematic random sampling from the list of staff in each
      representative institution. The study was conducted from November 2012 to
      February 2013. A total of 800 participants (590 from health centers and 210 from
      hospitals) were invited to participate in this study. RESULTS: A total number of
      763 healthcare professionals consented to participate. The overall response rate
      was 95 % with the majority being nurses, female staff and who had  an average of
      more than 4 years of experience. Overall, 85 % of the participants self-estimated
      awareness of the nine life-saving patient safety solutions showed the nurses
      being the most aware, followed by physicians with the allied health professionals
      showing suboptimal awareness. The primary healthcare center staff demonstrated
      higher awareness compared to hospital staff. There was a complex relationship
      between health professional's age, place of work and awareness and practice.
      CONCLUSION: This study lays the foundation for international comparisons of self
      estimated awareness and practice towards nine patient safety solutions. The data
      from Oman indicates the need for more attention to be directed towards
      heightening awareness and practice of the nine patient safety solutions.

PMID- 27716190
TI  - "I go I die, I stay I die, better to stay and die in my house": understanding the
      barriers to accessing health care in Timor-Leste.
AB  - BACKGROUND: Despite public health care being free at the point of delivery in
      Timor-Leste, wealthier patients access hospital care at nearly twice the rate of
      poorer patients. This study seeks to understand the barriers driving inequitable
      utilisation of hospital services in Timor-Leste from the perspective of community
      members and health care managers. METHODS: This multisite qualitative study in
      Timor-Leste conducted gender segregated focus groups (n = 8) in eight districts,
      with 59 adults in urban and rural settings, and in-depth interviews (n = 8) with
      the Director of community health centres. Communication was in the local
      language, Tetum, using a pre-tested interview schedule. Approval was obtained
      from community and national stakeholders, with written consent from participants.
      RESULTS: Lack of patient transport is the critical cross-cutting issue preventing
      access to hospital care. Without it, many communities resort to carrying patients
      by porters or on horseback, walking or paying for (unaffordable) private
      arrangements to reach hospital, or opt for home-based care. Other significant out
      of-pocket expenses for hospital visits were blood supplies from private
      suppliers; accommodation and food for the patient and family members; and
      repatriation of the deceased. Entrenched nepotism and hospital staff denigrating
      patients' hygiene and personal circumstances were also widely reported.
      Consequently, some respondents asserted they would never return to hospital,
      others delayed seeking treatment or interrupted their treatment to return home.
      Most considered traditional medicine provided an affordable, accessible and
      acceptable substitute to hospital care. Obtaining a referral for higher level
      care was not a significant barrier to gaining access to hospital care.
      CONCLUSIONS: Onerous physical, financial and socio-cultural barriers are
      preventing or discouraging people from accessing hospital care in Timor-Leste.
      Improving access to quality primary health care at the frontline is a key
      strategy for ensuring universal access to health care, pursued alongside
      initiatives to overcome the multi-faceted barriers to hospital care experienced
      by the vulnerable. Improving the availability and functioning of patient
      transport services, provision of travel subsidies to patients and their families
      and training hospital staff in standards of professional care are some options
      available to government and donors seeking faster progress towards universal
      health coverage in Timor-Leste.

PMID- 27716191
TI  - Comparison of different methods of splenic hilar lymph node dissection for
      advanced upper- and/or middle-third gastric cancer.
AB  - BACKGROUND: Surgery for advanced gastric cancer (AGC) often includes dissection
      of splenic hilar lymph nodes (SHLNs). This study compared the safety and
      effectiveness of different approaches to SHLN dissection for upper- and/or middle
      third AGC. METHODS: We retrospectively compared and analyzed clinicopathologic
      and follow-up data from a prospectively collected database at the Peking
      University Cancer Hospital. Patients were divided into three groups: in situ
      spleen-preserved, ex situ spleen-preserved and splenectomy. RESULTS: We analyzed
      217 patients with upper- and/or middle-third AGC who underwent R0 total or
      proximal gastrectomy with splenic hilar lymphadenectomy from January 2006 to
      December 2011, of whom 15.2 % (33/217) had metastatic SHLNs, and from whom 11.4 %
      (53/466) of the dissected SHLNs were metastatic. The number of harvested SHLNs
      per patient was higher in the ex situ group than in the in situ group (P =
      0.017). Length of postoperative hospital stay was longer in the splenectomy group
      than in the in situ group (P = 0.002) or the ex situ group (P < 0.001). The
      splenectomy group also lost more blood volume (P = 0.007) and had a higher
      postoperative complication rate (P = 0.005) than the ex situ group. Kaplan-Meier
      (log rank test) analysis showed significant survival differences among the three
      groups (P = 0.018). Multivariate analysis showed operation duration (P = 0.043),
      blood loss volume (P = 0.046), neoadjuvant chemotherapy (P = 0.005), and N stage
      (P < 0.001) were independent prognostic factors for survival. CONCLUSIONS: The ex
      situ procedure was more effective for SHLN dissection than the in situ procedure
      without sacrificing safety, whereas splenectomy was not more effective, and was
      less safe. The SHLN dissection method was not an independent risk factor for
      survival in this study.

PMID- 27716193
TI  - Keys to successful implementation of a French national quality indicator in
      health care organizations: a qualitative study.
AB  - BACKGROUND: Several countries have launched public reporting systems based on
      quality indicators (QIs) to increase transparency and improve quality in health
      care organizations (HCOs). However, a prerequisite to quality improvement is
      successful local QI implementation. The aim of this study was to explore the
      pathway through which a mandatory QI of the French national public reporting
      system, namely the quality of the anesthesia file (QAF), was put into practice.
      METHOD: Seven ethnographic case studies in French HCOs combining in situ
      observations and 37 semi-structured interviews. RESULTS: A significant proportion
      of potential QAF users, such as anesthetists or other health professionals were
      often unaware of quality data. They were, however, involved in improvement
      actions to meet the QAF criteria. In fact, three intertwined factors influenced
      QAF appropriation by anesthesia teams and impacted practice. The first factor was
      the action of clinical managers (chief anesthetists and head of department) who
      helped translate public policy into local practice largely by providing
      legitimacy by highlighting the scientific evidence underlying QAF, achieving
      consensus among team members, and pointing out the value of QAF as a means of
      work recognition. The two other factors related to the socio-material context,
      namely the coherence of information systems and the quality of interpersonal ties
      within the department. CONCLUSIONS: Public policy tends to focus on the
      metrological validity of QIs and on ranking methods and overlooks QI
      implementation. However, effective QI implementation depends on local managerial
      activity that is often invisible, in interaction with socio-material factors.
      When developing national quality improvement programs, health authorities might
      do well to specifically target these clinical managers who act as invaluable
      mediators. Their key role should be acknowledged and they ought to be provided
      with adequate resources.

PMID- 27716192
TI  - Sequence analysis of four vitamin D family genes (VDR, CYP24A1, CYP27B1 and
      CYP2R1) in Vogt-Koyanagi-Harada (VKH) patients: identification of a potentially
      pathogenic variant in CYP2R1.
AB  - BACKGROUND: VKH is a rare autoimmune disease. Decreased level of vitamin D has
      recently been found to be involved in the pathogenesis of Vogt-Koyanagi-Harada
      (VKH) disease. This study was designed to screen the vitamin D pathway genes for
      pathogenic mutations, if any, in VKH patients. METHODS: Genomic DNA was extracted
      from blood samples collected from patients with VKH disease and healthy controls.
      Entire coding region, exon-intron junctions of four genes were sequenced in DNA
      from 39 Saudi VKH patients and 50 ethnically matched healthy individuals. All
      patients and controls were unrelated. RESULTS: Vitamin D levels in VKH patients
      were found either insufficient (21-29 ng/mL) or deficient (<20 ng/mL). Sequencing
      analysis of the VDR, CYP24A1, CYP27B1 and CYP2R1 detected twelve nucleotide
      changes in these genes in our cohort of 39 patients; 4 of which were non-coding,
      6 were synonymous coding and 2 were non-synonymous coding sequence changes. All
      synonymous coding variants were benign polymorphisms with no apparent clinical
      significance. A non-synonymous coding sequence variant (c.2 T > C; p.1Met?) found
      in VDR is an initiation coding change and was detected in control individuals as
      well, while another variant (c.852G > A; p.284 M > I) found in CYP2R1 is
      predicted to be disease causing by mutationtaster software. This potentially
      pathogenic variant was found in 17 out of 39 VKH patients. CONCLUSIONS: Screening
      of four Vitamin D pathway genes in 39 VKH patients shows that a potentially
      pathogenic sequence variant in CYP2R1 may cause VKH in a subset of patients.
      These findings support the previous observation that low vitamin D levels might
      play a role in VKH pathogenesis and mutations in genes involved in vitamin D
      anabolism and catabolism might be of importance in VKH pathobiology.

PMID- 27716194
TI  - Design of an orthopaedic-specific discharge summary.
AB  - BACKGROUND: Patients undergoing orthopaedic procedures experience major changes
      in function and daily routines upon their return home. Discharge summaries are an
      important communication tool that may play a role in optimizing a safe transition
      from hospital. Current care gaps and key elements of an ideal discharge summary
      specific for orthopaedic population are unknown. We sought to identify the
      challenges of current orthopaedic discharge summaries and to determine key
      elements of an ideal document. METHODS: Qualitative study survey using semi
      structured interviews with a sample of 17 patients and clinicians representing
      diverse professions, backgrounds, and practice settings. We used the constant
      comparative method of qualitative analysis to define the experiences and
      perceptions of quality gaps and strategies to improve orthopaedic-specific
      discharge summaries. RESULTS: We identified 3 major themes describing factors
      perceived to be limiting the quality of current discharge summaries: 1) physician
      centric documentation and the absence of a comprehensive, inter-professional
      perspective; 2) access to resources and health informatics; and 3) process
      variations in document creation and dissemination. CONCLUSIONS: Clinicians and
      patients identified several factors limiting the quality of discharge summaries
      among orthopaedic inpatients. Incorporating these elements could improve hospital
      transitions.

PMID- 27716196
TI  - Testing the construct validity of hospital care quality indicators: a case study
      on hip replacement.
AB  - BACKGROUND: Quality indicators are increasingly used to measure the quality of
      care and compare quality across hospitals. In the Netherlands over the past few
      years numerous hospital quality indicators have been developed and reported.
      Dutch indicators are mainly based on expert consensus and face validity and
      little is known about their construct validity. Therefore, we aim to study the
      construct validity of a set of national hospital quality indicators for hip
      replacements. METHODS: We used the scores of 100 Dutch hospitals on national
      hospital quality indicators looking at care delivered over a two year period. We
      assessed construct validity by relating structure, process and outcome indicators
      using chi-square statistics, bootstrapped Spearman correlations, and independent
      sample t-tests. We studied indicators that are expected to associate as they
      measure the same clinical construct. RESULT: Among the 28 hypothesized
      correlations, three associations were significant in the direction hypothesized.
      Hospitals with low scores on wound infections had high scores on scheduling
      postoperative appointments (p-value = 0.001) and high scores on not transfusing
      homologous blood (correlation coefficient = -0.28; p-value = 0.05). Hospitals
      with high scores on scheduling complication meetings, also had high scores on
      providing thrombosis prophylaxis (correlation coefficient = 0.21; p-value =
      0.04). CONCLUSION: Despite the face validity of hospital quality indicators for
      hip replacement, construct validity seems to be limited. Although the individual
      indicators might be valid and actionable, drawing overall conclusions based on
      the whole indicator set should be done carefully, as construct validity could not
      be established. The factors that may explain the lack of construct validity are
      poor data quality, no adjustment for case-mix and statistical uncertainty.

PMID- 27716195
TI  - Sarcopenia in daily practice: assessment and management.
AB  - BACKGROUND: Sarcopenia is increasingly recognized as a correlate of ageing and is
      associated with increased likelihood of adverse outcomes including falls,
      fractures, frailty and mortality. Several tools have been recommended to assess
      muscle mass, muscle strength and physical performance in clinical trials. Whilst
      these tools have proven to be accurate and reliable in investigational settings,
      many are not easily applied to daily practice. METHODS: This paper is based on
      literature reviews performed by members of the European Society for Clinical and
      Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on
      frailty and sarcopenia. Face-to-face meetings were afterwards organized for the
      whole group to make amendments and discuss further recommendations. RESULTS: This
      paper proposes some user-friendly and inexpensive methods that can be used to
      assess sarcopenia in real-life settings. Healthcare providers, particularly in
      primary care, should consider an assessment of sarcopenia in individuals at
      increased risk; suggested tools for assessing risk include the Red Flag Method,
      the SARC-F questionnaire, the SMI method or different prediction equations.
      Management of sarcopenia should primarily be patient centered and involve the
      combination of both resistance and endurance based activity programmes with or
      without dietary interventions. Development of a number of pharmacological
      interventions is also in progress. CONCLUSIONS: Assessment of sarcopenia in
      individuals with risk factors, symptoms and/or conditions exposing them to the
      risk of disability will become particularly important in the near future.

PMID- 27716197
TI  - Dietary intake patterns of children aged 6 years and their association with
      socioeconomic and demographic characteristics, early feeding practices and body
      mass index.
AB  - BACKGROUND: Dietary intake patterns of children from the 2004 Pelotas birth
      cohort study have been described at 12, 24 and 48 months of age, but there is no
      information about dietary patterns of these children at 6 years. Then, we aimed
      to identify and describe dietary intake patterns of children aged 6 years as well
      as to assess their association with socioeconomic and demographic
      characteristics, early feeding practices and BMI z-score at 6 years. METHODS: We
      used principal components analysis to identify dietary intake patterns of 3,427
      children from the 2004 Pelotas (Brazil) birth cohort study. We used multiple
      linear regression models to evaluate whether socioeconomic and demographic
      characteristics (socioeconomic position, mother's age at birth, and child's sex
      and skin colour), early feeding practices (exclusive breastfeeding duration and
      age of introduction of complementary foods), and BMI z-score at 6 years were
      associated with dietary intake patterns. RESULTS: We identified seven dietary
      components of children's dietary intake patterns, namely: fruits and vegetables,
      snacks and treats, coffee and bread, milk, cheese and processed meats, rice and
      beans and carbohydrates. Dietary patterns were socially patterned, since six
      dietary components were associated with socioeconomic position. Moreover, high
      intake of snacks and treats and less fruits and vegetables were associated with
      children born to teenage mothers, with those exclusively breastfed for less than
      one month, and with those who started on complementary feeding before 4 months.
      Finally, overweight and obese children at 6 years presented lower intake of four
      out of seven dietary components, but we need to be cautious in interpretation due
      to limitations on food consumption reporting and due to possible reverse
      causality. CONCLUSION: Dietary intake patterns in children are strongly
      influenced by socioeconomic characteristics. Other factors such as younger
      maternal age at birth, and both early weaning and early introduction of
      complementary feeding appear to be related with 'unhealthier' patterns.
      Overweight and obese children presented lower intake of four out of seven dietary
      components, but further studies would be interesting to understand the
      longitudinal effect of children's feeding practices on BMI and adiposity.

PMID- 27716198
TI  - Identifying neuropsychiatric disorders in the Medicare Current Beneficiary
      Survey: the benefits of combining health survey and claims data.
AB  - BACKGROUND: To address the impact of using multiple sources of data in the United
      States Medicare Current Beneficiary Survey (MCBS) compared to using only one
      source of data to identify those with neuropsychiatric diagnoses. METHODS: Our
      data source was the 2010 MCBS with associated Medicare claims files (N = 14, 672
      beneficiaries). The MCBS uses a stratified multistage probability sample design
      to select a nationally representative sample of Medicare beneficiaries. We
      excluded those participants in Medicare Health Maintenance Organizations (n =
      3894) and performed a cross-sectional analysis. We classified neuropsychiatric
      conditions according to four broad categories: intellectual/developmental
      disorders, neurological conditions affecting the central nervous system (Neuro
      CNS), dementia, and psychiatric conditions. To account for different baseline
      prevalence differences of the categories we calculated the relative increase in
      prevalence that occurred from adding information from claims in addition to the
      absolute increase to allow comparison among categories. RESULTS: The estimated
      proportion of the sample with neuropsychiatric disorders increased to 50.0 (both
      sources) compared to 38.9 (health survey only) and 33.2 (claims only) with an
      overlap between sources of only 44.1 %. Augmenting health survey data with claims
      led to an increase in estimated percentage of intellectual/developmental
      disorders, psychiatric disorders, Neuro-CNS disorders and dementia of 1.3, 5.9,
      11.5 and 3.8 respectively. In the community sample, the largest relative
      increases were seen for dementia (147.6 %) and Neuro-CNS disorders (87.4 %). With
      the exception of dementia, larger relative increases were seen in the facility
      sample with the greatest being for intellectual/developmental disorders (121.5 %)
      and Neuro-CNS disorders (93.8 %). CONCLUSIONS: The magnitude of potentially
      underestimated sample proportions using health survey only data varied strikingly
      according to the category of diagnosis and setting. Augmentation of survey data
      with claims appears essential particularly when attempting to estimate proportion
      of the sample affected by conditions that cause cognitive impairment which may
      affect ability to self-report. Augmenting proxy survey data with claims data also
      appears to be essential when ascertaining proportion of the facility-dwelling
      sample affected by neuropsychiatric disorders.

PMID- 27716199
TI  - PRognostic factor of Early Death In phase II Trials or the end of 'sufficient
      life expectancy' as an inclusion criterion? (PREDIT model).
AB  - BACKGROUND: Optimizing patient selection is a necessary step to design better
      clinical trials. 'Life expectancy' is a frequent inclusion criterion in phase II
      trial protocols, a measure that is subjective and often difficult to estimate.
      The aim of this study was to identify factors associated with early death in
      patients included in phase II studies. METHODS: We retrospectively collected
      medical records of patients with advanced solid tumors included in phase II
      trials in two French Comprehensive Cancer Centers (Bordeaux, Center 1 set; Lille,
      Center 2 set). We analyzed patients' baseline characteristics. Predictive factors
      associated with early death (mortality at 3 months) were identified by logistic
      regression. We built a model (PREDIT, PRognostic factor of Early Death In phase
      II Trials) based on prognostic factors isolated from the final multivariate
      model. RESULTS: Center 1 and 2 sets included 303 and 227 patients, respectively.
      Patients from Center 1 and 2 sets differed in tumor site, urological (26 % vs 15
      %) and gastrointestinal (18 % vs 28 %) and in lung metastasis incidence (10 % vs
      49 %). Overall survival (OS) at 3 months was 88 % (95 % CI [83.5; 91.0], Center 1
      set) and 91 % (95 % CI [86.7; 94.2], Center 2 set). Presence of a 'life
      expectancy' inclusion criterion did not improve the 3-month OS (HR 0.6, 95 % CI
      [0.2; 1.2], p = 0.2325). Independent factors of early death were an ECOG score of
      2 (OR 13.3, 95%CI [4.1; 43.4]), hyperleukocytosis (OR 5.5, 95 % CI [1.9; 16.3])
      and anemia (OR 2.8, 95 % CI [1.1; 7.1]). Same predictive factors but with
      different association levels were found in the Center 2 set. Using the Center 1
      set, ROC analysis shows a good discrimination to predict early death (AUC: 0.89
      at 3 months and 0.86 at 6 months). CONCLUSIONS: Risk modeling in two independent
      cancer populations based on simple clinical parameters showed that baseline ECOG
      of 2, hyperleukocytosis and anemia are strong early-death predictive factors.
      This model allows identifying patients who may not benefit from a phase II trial
      investigational drug and may, therefore, represent a helpful tool to select
      patients for phase II trial entry.

PMID- 27716200
TI  - Implementing multifactorial psychotherapy research in online virtual environments
      (IMPROVE-2): study protocol for a phase III trial of the MOST randomized
      component selection method for internet cognitive-behavioural therapy for
      depression.
AB  - BACKGROUND: Depression is a global health challenge. Although there are effective
      psychological and pharmaceutical interventions, our best treatments achieve
      remission rates less than 1/3 and limited sustained recovery. Underpinning this
      efficacy gap is limited understanding of how complex psychological interventions
      for depression work. Recent reviews have argued that the active ingredients of
      therapy need to be identified so that therapy can be made briefer, more potent,
      and to improve scalability. This in turn requires the use of rigorous study
      designs that test the presence or absence of individual therapeutic elements,
      rather than standard comparative randomised controlled trials. One such approach
      is the Multiphase Optimization Strategy, which uses efficient experimentation
      such as factorial designs to identify active factors in complex interventions.
      This approach has been successfully applied to behavioural health but not yet to
      mental health interventions. METHODS/DESIGN: A Phase III randomised, single-blind
      balanced fractional factorial trial, based in England and conducted on the
      internet, randomized at the level of the patient, will investigate the active
      ingredients of internet cognitive-behavioural therapy (CBT) for depression.
      Adults with depression (operationalized as PHQ-9 score >= 10), recruited directly
      from the internet and from an UK National Health Service Improving Access to
      Psychological Therapies service, will be randomized across seven experimental
      factors, each reflecting the presence versus absence of specific treatment
      components (activity scheduling, functional analysis, thought challenging,
      relaxation, concreteness training, absorption, self-compassion training) using a
      32-condition balanced fractional factorial design (2IV7-2). The primary outcome
      is symptoms of depression (PHQ-9) at 12 weeks. Secondary outcomes include
      symptoms of anxiety and process measures related to hypothesized mechanisms.
      DISCUSSION: Better understanding of the active ingredients of efficacious
      therapies, such as CBT, is necessary in order to improve and further disseminate
      these interventions. This study is the first application of a component selection
      experiment to psychological interventions in depression and will enable us to
      determine the main effect of each treatment component and its relative efficacy,
      and cast light on underlying mechanisms, so that we can systematically enhance
      internet CBT. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24117387 .
      Registered 26 August 2014.

PMID- 27716201
TI  - Should all acutely ill children in primary care be tested with point-of-care CRP:
      a cluster randomised trial.
AB  - BACKGROUND: Point-of-care blood C-reactive protein (CRP) testing has diagnostic
      value in helping clinicians rule out the possibility of serious infection. We
      investigated whether it should be offered to all acutely ill children in primary
      care or restricted to those identified as at risk on clinical assessment.
      METHODS: Cluster randomised controlled trial involving acutely ill children
      presenting to 133 general practitioners (GPs) at 78 GP practices in Belgium.
      Practices were randomised to undertake point-of-care CRP testing in all children
      (1730 episodes) or restricted to children identified as at clinical risk (1417
      episodes). Clinical risk was assessed by a validated clinical decision rule
      (presence of one of breathlessness, temperature >= 40  degrees C, diarrhoea and
      age 12-30 months, or clinician concern). The main trial outcome was hospital
      admission with serious infection within 5 days. No specific guidance was given to
      GPs on interpreting CRP levels but diagnostic performance is reported at 5, 20,
      80 and 200 mg/L. RESULTS: Restricting CRP testing to those identified as at
      clinical risk substantially reduced the number of children tested by 79.9 % (95 %
      CI, 77.8-82.0 %). There was no significant difference between arms in the number
      of children with serious infection who were referred to hospital immediately
      (0.16 % vs. 0.14 %, P = 0.88). Only one child with a CRP < 5 mg/L had an illness
      requiring admission (a child with viral gastroenteritis admitted for
      rehydration). However, of the 80 children referred to hospital to rule out
      serious infection, 24 (30.7 %, 95 % CI, 19.6-45.6 %) had a CRP < 5 mg/L.
      CONCLUSIONS: CRP testing should be restricted to children at higher risk after
      clinical assessment. A CRP < 5 mg/L rules out serious infection and could be used
      by GPs to avoid unnecessary hospital referrals. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02024282 (registered on 14th September 2012).

PMID- 27716202
TI  - Proteomic analysis of the signaling pathway mediated by the heterotrimeric Galpha
      protein Pga1 of Penicillium chrysogenum.
AB  - BACKGROUND: The heterotrimeric Galpha protein Pga1-mediated signaling pathway
      regulates the entire developmental program in Penicillium chrysogenum, from spore
      germination to the formation of conidia. In addition it participates in the
      regulation of penicillin biosynthesis. We aimed to advance the understanding of
      this key signaling pathway using a proteomics approach, a powerful tool to
      identify effectors participating in signal transduction pathways. RESULTS:
      Penicillium chrysogenum mutants with different levels of activity of the Pga1
      mediated signaling pathway were used to perform comparative proteomic analyses by
      2D-DIGE and LC-MS/MS. Thirty proteins were identified which showed differences in
      abundance dependent on Pga1 activity level. By modifying the intracellular levels
      of cAMP we could establish cAMP-dependent and cAMP-independent pathways in Pga1
      mediated signaling. Pga1 was shown to regulate abundance of enzymes in primary
      metabolic pathways involved in ATP, NADPH and cysteine biosynthesis, compounds
      that are needed for high levels of penicillin production. An in vivo
      phosphorylated protein containing a pleckstrin homology domain was identified;
      this protein is a candidate for signal transduction activity. Proteins with
      possible roles in purine metabolism, protein folding, stress response and
      morphogenesis were also identified whose abundance was regulated by Pga1
      signaling. CONCLUSIONS: Thirty proteins whose abundance was regulated by the Pga1
      mediated signaling pathway were identified. These proteins are involved in
      primary metabolism, stress response, development and signal transduction. A model
      describing the pathways through which Pga1 signaling regulates different cellular
      processes is proposed.

PMID- 27716203
TI  - Marital status, widowhood duration, gender and health outcomes: a cross-sectional
      study among older adults in India.
AB  - BACKGROUND: Previous research has demonstrated health benefits of marriage and
      the potential for worse outcomes during widowhood in some populations. However,
      few studies have assessed the relevance of widowhood and widowhood duration to a
      variety of health-related outcomes and chronic diseases among older adults in
      India, and even fewer have examined these relationships stratified by gender.
      METHODS: Using a cross-sectional representative sample of 9,615 adults aged 60
      years or older from 7 states in diverse regions of India, we examine the
      relationship between widowhood and self-rated health, psychological distress,
      cognitive ability, and four chronic diseases before and after adjusting for
      demographic characteristics, socioeconomic status, living with children, and
      rural-urban location for men and women, separately. We then assess these
      associations when widowhood accounts for duration. RESULTS: Being widowed as
      opposed to married was associated with worse health outcomes for women after
      adjusting for other explanatory factors. Widowhood in general was not associated
      with any outcomes for men except for cognitive ability, though men who were
      widowed within 0-4 years were at greater risk for diabetes compared to married
      men. Moreover, recently widowed women and women who were widowed long-term were
      more likely to experience psychological distress, worse self-rated health, and
      hypertension, even after adjusting for other explanatory variables, whereas women
      widowed 5-9 years were not, compared to married women. CONCLUSIONS: Gender, the
      duration of widowhood, and type of outcome are each relevant pieces of
      information when assessing the potential for widowhood to negatively impact
      health. Future research should explore how the mechanisms linking widowhood to
      health vary over the course of widowhood. Incorporating information about marital
      relationships into the design of intervention programs may help better target
      potential beneficiaries among older adults in India.

PMID- 27716205
TI  - Effects of inhaled high-molecular weight hyaluronan in inflammatory airway
      disease.
AB  - Cystic fibrosis (CF) is a chronic inflammatory disease that is affecting
      thousands of patients worldwide. Adjuvant anti-inflammatory treatment is an
      important component of cystic fibrosis treatment, and has shown promise in
      preserving lung function and prolonging life expectancy. Inhaled high molecular
      weight hyaluronan (HMW-HA) is reported to improve tolerability of hypertonic
      saline and thus increase compliance, and has been approved in some European
      countries for use as an adjunct to hypertonic saline treatment in cystic
      fibrosis. However, there are theoretical concerns that HMW-HA breakdown products
      may be pro-inflammatory. In this clinical pilot study we show that sputum
      cytokines in CF patients receiving HMW-HA are not increased, and therefore HMW-HA
      does not appear to adversely affect inflammatory status in CF airways.

PMID- 27716204
TI  - Insulin-like growth factor 1 receptor mediated tyrosine 845 phosphorylation of
      epidermal growth factor receptor in the presence of monoclonal antibody
      cetuximab.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) is frequently
      overexpressed in head and neck squamous cell carcinoma (HNSCC) and several other
      human cancers. Monoclonal antibodies, such as cetuximab that block EGFR
      signaling, have emerged as valuable molecular targeting agents in clinical cancer
      therapy. Prolonged exposure to cetuximab can result in cells acquiring resistance
      by a process that remains incompletely understood. METHODS: In this study, we
      analyzed the immediate early molecular response of cetuximab on physical
      interactions between EGFR and Insulin growth factor 1 like receptor (IGF-1R) in
      head and neck cancer cells that are resistant to cetuximab. Co
      immunoprecipitation, small molecule inhibitors against phospho-Src and IGF-1R,
      quantitative western blot of EGFR and Src phosphorylation, cell proliferation
      assays were used to suggest the role of IGF-1R mediated phosphorylation of
      specific tyrosine Y845 on EGFR via increased heterodimerization of EGFR and IGF
      1R in cetuximab resistant cells. RESULTS: Heterodimerization of EGFR with IGF-1R
      was increased in cetuximab resistant HNSCC cell line UMSCC6. Basal levels of
      phosphorylated EGFR Y845 showed significant increase in the presence of
      cetuximab. Surprisingly, this activated Y845 level was not inhibited in the
      presence of Src inhibitor PP1. Instead, inhibition of IGF-1R by picropodophyllin
      (PPP) reduced the EGFR Y845 levels. Taken together, these results suggest that
      heterodimerization of EGFR with IGF-1R can lead to increased activity of EGFR and
      may be an important platform for cetuximab mediated signaling in head and neck
      tumors that have become resistant to anti-EGFR therapy. CONCLUSIONS: EGFR-IGF-1R
      interaction has a functional consequence of phosphorylation of EGFR Y845 in
      cetuximab resistant HNSCC cells and dual targeting of EGFR and IGF-1R is a
      promising therapeutic strategy.

PMID- 27716206
TI  - Association of serum calcium and heart failure with preserved ejection fraction
      in patients with type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a recognized trigger factor for
      heart failure with preserved ejection fraction (HFpEF). Recent studies show that
      higher serum calcium level is associated with greater risk of both T2DM and heart
      failure. We speculate that increased serum calcium is related to HFpEF prevalence
      in patients with T2DM. METHODS: In this cross-sectional echocardiographic study,
      807 normocalcemia and normophosphatemia patients with T2DM participated, of whom
      106 had HFpEF. Multinomial logistic regression was carried out to determine the
      variables associated with HFpEF. The associations between serum calcium and
      metabolic parameters, as well as the rate of HFpEF were examined using bivariate
      linear correlation and binary logistic regression, respectively. The predictive
      performance of serum calcium for HFpEF was evaluated using the area under the
      receiver operating characteristic curve (AUC). RESULTS: Patients with HFpEF have
      significantly higher serum calcium than those without HFpEF. Serum calcium was
      positively associated with total cholesterol, triglycerides, low-density
      lipoprotein cholesterol, serum uric acid, HOMA-IR and fasting plasma glucose.
      Compared with patients in the lowest serum calcium quartile, the odds ratio (OR)
      for HFpEF in patients in the highest quartile was 2.331 (95 % CI 1.088-4.994, p =
      0.029). When calcium was analyzed as a continuous variable, per 1 mg/dL increase,
      the OR (95 % CI) for HFpEF was [2.712 (1.471-5.002), p = 0.001]. Serum calcium
      can predict HFpEF [AUC = 0.673, 95 % CI (0.620-0.726), p < 0.001]. CONCLUSIONS:
      An increase in serum calcium level is associated with an increased risk of HFpEF
      in patients with T2DM.

PMID- 27716207
TI  - A fast linear predictive adaptive model of packed bed coupled with UASB reactor
      treating onion waste to produce biofuel.
AB  - BACKGROUND: Agro-industrial wastes are an energy source for different industries.
      However, its application has not reached small industries. Previous and current
      research activities performed on the acidogenic phase of two-phase anaerobic
      digestion processes deal particularly with process optimization of the acid-phase
      reactors operating with a wide variety of substrates, both soluble and complex in
      nature. Mathematical models for anaerobic digestion have been developed to
      understand and improve the efficient operation of the process. At present, lineal
      models with the advantages of requiring less data, predicting future behavior and
      updating when a new set of data becomes available have been developed. The aim of
      this research was to contribute to the reduction of organic solid waste, generate
      biogas and develop a simple but accurate mathematical model to predict the
      behavior of the UASB reactor. RESULTS: The system was maintained separate for 14
      days during which hydrolytic and acetogenic bacteria broke down onion waste,
      produced and accumulated volatile fatty acids. On this day, two reactors were
      coupled and the system continued for 16 days more. The biogas and methane yields
      and volatile solid reduction were 0.6 +/- 0.05 m3 (kg VSremoved)-1, 0.43 +/- 0.06
      m3 (kg VSremoved)-1 and 83.5 +/- 9.8 %, respectively. The model application
      showed a good prediction of all process parameters defined; maximum error between
      experimental and predicted value was 1.84 % for alkalinity profile. CONCLUSIONS:
      A linear predictive adaptive model for anaerobic digestion of onion waste in a
      two-stage process was determined under batch-fed condition. Organic load rate
      (OLR) was maintained constant for the entire operation, modifying effluent
      hydrolysis reactor feed to UASB reactor. This condition avoids intoxication of
      UASB reactor and also limits external buffer addition.

PMID- 27716208
TI  - Service readiness, health facility management practices, and delivery care
      utilization in five states of Nigeria: a cross-sectional analysis.
AB  - BACKGROUND: Existing studies of delivery care in Nigeria have identified
      socioeconomic and cultural factors as the primary determinants of health facility
      delivery. However, no study has investigated the association between supply-side
      factors and health facility delivery. Our study analyzed the role of supply-side
      factors, particularly health facility readiness and management practices for
      provision of quality maternal health services. METHODS: Using linked data from
      the 2005 and 2009 health facility and household surveys in the five states in
      which the Community Participation for Action in the Social Sector (COMPASS)
      project was implemented, indices of health service readiness and management were
      developed based on World Health Organization guidelines. Multilevel logistic
      regression models were run to determine the association between these indices and
      health facility delivery among 2710 women aged 15-49 years whose last child was
      born within the five years preceding the surveys and who lived in 51 COMPASS
      LGAs. RESULTS: The health facility delivery rate increased from 25.4 % in 2005 to
      44.1 % in 2009. Basic amenities for antenatal care provision, readiness to
      deliver basic emergency obstetric and newborn care, and management practices
      supportive of quality maternal health services were suboptimal in health
      facilities surveyed and did not change significantly between 2005 and 2009. The
      LGA mean index of basic amenities for antenatal care provision was more
      positively associated with the odds of health facility delivery in 2009 than in
      2005, and in rural than in urban areas. The LGA mean index of management
      practices was associated with significantly lower odds of health facility
      delivery in rural than in urban areas. The LGA mean index of facility readiness
      to deliver basic emergency obstetric and neonatal care declined slightly from
      5.16 in 2005 to 3.98 in 2009 and was unrelated to the odds of health facility
      delivery. CONCLUSION: Supply-side factors appeared to play a role in health
      facility delivery after controlling for socio-demographic factors. Improving
      uptake of delivery care would require greater attention to rural-urban inequities
      and health facility management practices, and to increasing the number of health
      facilities with fundamental elements for delivery of basic emergency obstetric
      and neonatal care.

PMID- 27716209
TI  - Effects of testosterone treatment on body fat and lean mass in obese men on a
      hypocaloric diet: a randomised controlled trial.
AB  - BACKGROUND: Whether testosterone treatment has benefits on body composition over
      and above caloric restriction in men is unknown. We hypothesised that
      testosterone treatment augments diet-induced loss of fat mass and prevents loss
      of muscle mass. METHODS: We conducted a randomised double-blind, parallel,
      placebo controlled trial at a tertiary referral centre. A total of 100 obese men
      (body mass index >= 30 kg/m2) with a total testosterone level of or below 12
      nmol/L and a median age of 53 years (interquartile range 47-60) receiving 10
      weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance
      were randomly assigned at baseline to 56 weeks of 10-weekly intramuscular
      testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls).
      The main outcome measures were the between-group difference in fat and lean mass
      by dual-energy X-ray absorptiometry, and visceral fat area (computed tomography).
      RESULTS: A total of 82 men completed the study. At study end, compared to
      controls, cases had greater reductions in fat mass, with a mean adjusted between
      group difference (MAD) of -2.9 kg (-5.7 to -0.2; P = 0.04), and in visceral fat
      (MAD -2678 mm2; -5180 to -176; P = 0.04). Although both groups lost the same lean
      mass following VLED (cases -3.9 kg (-5.3 to -2.6); controls -4.8 kg (-6.2 to 
      3.5), P = 0.36), cases regained lean mass (3.3 kg (1.9 to 4.7), P < 0.001) during
      weight maintenance, in contrast to controls (0.8 kg (-0.7 to 2.3), P = 0.29) so
      that, at study end, cases had an attenuated reduction in lean mass compared to
      controls (MAD 3.4 kg (1.3 to 5.5), P = 0.002). CONCLUSIONS: While dieting men
      receiving placebo lost both fat and lean mass, the weight loss with testosterone
      treatment was almost exclusively due to loss of body fat. TRIAL REGISTRATION:
      clinicaltrials.gov, identifier NCT01616732 , registration date: June 8, 2012.

PMID- 27716210
TI  - A cross-sectional study of physical activity and sedentary behaviours in a
      Caribbean population: combining objective and questionnaire data to guide future
      interventions.
AB  - BACKGROUND: Current understanding of population physical activity (PA) levels and
      sedentary behaviour in developing countries is limited, and based primarily on
      self-report. We described PA levels using objective and self-report methods in a
      developing country population. METHODS: PA was assessed in a cross-sectional,
      representative sample of the population of Barbados (25-54 years), using a
      validated questionnaire (RPAQ) and individually calibrated combined heart rate
      and movement sensing monitors. The RPAQ collects information on recalled activity
      in 4 domains: home, work, transport, and leisure. Physical inactivity was defined
      according to World Health Organization (WHO) guidelines; sedentary lifestyle was
      defined as being sedentary for 8 h or more daily; PA overestimation was defined
      as perceiving activity to be sufficient, when classified as 'inactive' by
      objective measurement. RESULTS: According to objective estimates, 90.5 % (95 %
      CI: 83.3,94.7) of women and 58.9 % (48.4,68.7) of men did not accumulate
      sufficient activity to meet WHO minimum recommendations. Overall, 50.7 %
      (43.3,58.1) of the population was sedentary for 8 h or more each day, and 60.1 %
      (52.8,66.9) overestimated their activity levels. The prevalence of inactivity was
      underestimated by self-report in both genders by 28 percentage points (95 % CI:
      18,38), but the accuracy of reporting differed by age group, education level,
      occupational grade, and overweight/obesity status. Low PA was greater in more
      socially privileged groups: higher educational level and higher occupational
      grade were both associated with less objectively measured PA and more sedentary
      time. Variation in domain-specific self-reported physical activity energy
      expenditure (PAEE) by educational attainment was observed: higher education level
      was associated with more leisure activity and less occupational activity.
      Occupational PA was the main driver of PAEE for women and men according to self
      report, contributing 57 % (95 % CI: 52,61). The most popular leisure activities
      for both genders were walking and gardening. CONCLUSIONS: The use of both
      objective and self-report methods to assess PA and sedentary behaviour provides
      important complementary information to guide public health programmes. Our
      results emphasize the urgent need to increase PA and reduce sedentary time in
      this developing country population. Women and those with higher social economic
      position are particularly at risk from low levels of physical activity.

PMID- 27716211
TI  - A 19-SNP coronary heart disease gene score profile in subjects with type 2
      diabetes: the coronary heart disease risk in type 2 diabetes (CoRDia study) study
      baseline characteristics.
AB  - BACKGROUND: The coronary risk in diabetes (CoRDia) trial (n = 211) compares the
      effectiveness of usual diabetes care with a self-management intervention (SMI),
      with and without personalised risk information (including genetics), on clinical
      and behavioural outcomes. Here we present an assessment of randomisation, the
      cardiac risk genotyping assay, and the genetic characteristics of the recruits.
      METHODS: Ten-year coronary heart disease (CHD) risk was calculated using the
      UKPDS score. Genetic CHD risk was determined by genotyping 19 single nucleotide
      polymorphisms (SNPs) using Randox's Cardiac Risk Prediction Array and calculating
      a gene score (GS). Accuracy of the array was assessed by genotyping a subset of
      pre-genotyped samples (n = 185). RESULTS: Overall, 10-year CHD risk ranged from 2
      72 % but did not differ between the randomisation groups (p = 0.13). The array
      results were 99.8 % concordant with the pre-determined genotypes. The GS did not
      differ between the Caucasian participants in the CoRDia SMI plus risk group (n =
      66) (p = 0.80) and a sample of UK healthy men (n = 1360). The GS was also
      associated with LDL-cholesterol (p = 0.05) and family history (p = 0.03) in a
      sample of UK healthy men (n = 1360). CONCLUSIONS: CHD risk is high in this group
      of T2D subjects. The risk array is an accurate genotyping assay, and is suitable
      for estimating an individual's genetic CHD risk. Trial registration This study
      has been registered at ClinicalTrials.gov; registration identifier NCT01891786.

PMID- 27716213
TI  - Use of non-emergency contraceptive pills and concoctions as emergency
      contraception among Nigerian University students: results of a qualitative study.
AB  - BACKGROUND: Emergency contraception (EC) can significantly reduce the rate of
      unintended pregnancies and unsafe abortions especially in sub-Saharan Africa.
      Despite the increasing awareness of EC among educated young women in Nigeria, the
      rate of utilisation remains low. This study therefore explores the main barriers
      to the use of EC among female university students by analysing their knowledge of
      emergency contraception, methods ever used, perceived efficacy, and its
      acceptability. METHODS: This paper brings together the findings from several
      focus groups (N = 5) and in-depth interviews (N = 20) conducted amongst unmarried
      female undergraduate students in two Nigerian universities. RESULTS: Participants
      considered the use of condom and abstinence as the most effective methods of
      preventing unplanned pregnancy. However, many participants were misinformed about
      emergency contraception. Generally, participants relied on unconventional and
      unproven ECs; Ampiclox, "Alabukun", salt water solution, and lime and potash and
      perceived them to be effective in preventing unplanned pregnancies. Furthermore,
      respondents' narratives about methods of preventing unwanted pregnancies revealed
      that inadequate information on emergency contraception, reliance on unproven
      crude contraceptive methods, and misconception about modern contraception
      constitute barriers to the use of emergency contraception. CONCLUSIONS: The
      findings suggested that female university students are misinformed about
      emergency contraception and their reliance on unproven ECs constitutes a barrier
      to the use of approved EC methods. These barriers have serious implications for
      prevention of unplanned pregnancies in the cohort. Behavioural interventions
      targeting the use of unproven emergency contraceptive methods and misperceptions
      about ECs would be crucial for this cohort in Nigeria.

PMID- 27716212
TI  - Anti-inflammatory potential of PI3Kdelta and JAK inhibitors in asthma patients.
AB  - BACKGROUND: Phosphatidylinositol 3-kinase delta (PI3Kdelta) and Janus-activated
      kinases (JAK) are both novel anti-inflammatory targets in asthma that affect
      lymphocyte activation. We have investigated the anti-inflammatory effects of
      PI3Kdelta and JAK inhibition on cytokine release from asthma bronchoalveolar
      lavage (BAL) cells and T-cell activation, and measured lung PI3Kdelta and JAK
      signalling pathway expression. METHOD: Cells isolated from asthma patients and
      healthy subjects were treated with PI3Kdelta or JAK inhibitors, and/or
      dexamethasone, before T-cell receptor stimulation. Levels of IFNgamma, IL-13 and
      IL-17 were measured by ELISA and flow cytometry was used to assess T-cell
      activation. PI3Kdelta, PI3Kgamma, phosphorylated protein kinase B (pAKT) and
      Signal Transducer and Activator of Transcription (STAT) protein expression were
      assessed by immunohistochemistry in bronchial biopsy tissue from asthma patients
      and healthy subjects. PI3Kdelta expression in BAL CD3 cells was measured by flow
      cytometry. RESULTS: JAK and PI3Kdelta inhibitors reduced cytokine levels from
      both asthma and healthy BAL cells. Combining dexamethasone with either a JAK or
      PI3Kdelta inhibitor showed an additive anti-inflammatory effect. JAK and
      PI3Kdelta inhibitors were shown to have direct effects on T-cell activation.
      Immunohistochemistry showed increased numbers of PI3Kdelta expressing cells in
      asthma bronchial tissue compared to controls. Asthma CD3 cells in BAL expressed
      higher levels of PI3Kdelta protein compared to healthy cells. CONCLUSIONS:
      Targeting PI3Kdelta or JAK may prove effective in reducing T-cell activation and
      the resulting cytokine production in asthma.

PMID- 27716214
TI  - Administration of AMD3100 in endotoxemia is associated with pro-inflammatory, pro
      oxidative, and pro-apoptotic effects in vivo.
AB  - BACKGROUND: Chemokine receptor 4 (CXCR4) is a multifunctional G protein-coupled
      receptor that is activated by its natural ligand, C-X-C motif chemokine 12
      (CXCL12). As a likely member of the lipopolysaccharide (LPS)-sensing complex,
      CXCR4 is involved in pro-inflammatory cytokine production and exhibits
      substantial chemo-attractive activity for various inflammatory cells. Here, we
      aimed to characterize the effects of CXCR4 blockade in systemic inflammation and
      to evaluate its impact on organ function. Furthermore, we investigated whether
      CXCR4 blockade exerts deleterious effects, thereby substantiating previous
      studies showing a beneficial outcome after treatment with CXCR4 agonists in
      endotoxemia. METHODS: The CXCR4 antagonist AMD3100 was administered
      intraperitoneally to mice shortly after LPS treatment. After 24 h, health status
      was determined and serum tumor necrosis factor alpha (TNF alpha), interferon
      gamma (IFN gamma), and nitric oxide (NO) levels were measured. We further
      assessed oxidative stress in the brain, kidney, and liver as well as liver
      biotransformation capacity. Finally, we utilized immunohistochemistry and
      immunoblotting in liver and spleen tissue to determine cluster of differentiation
      3 (CD3), CD8, CD68, and TNF alpha expression patterns, and to assess the presence
      of various markers for apoptosis and oxidative stress. RESULTS: Mice treated with
      AMD3100 displayed impaired health status and showed enhanced serum levels of TNF
      alpha, IFN gamma and NO levels in endotoxemia. This compound also amplified LPS
      induced oxidative stress in all tissues investigated and decreased liver
      biotransformation capacity in co-treated animals. Co-treatment with AMD3100
      further inhibited expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf
      2), heme oxygenase-1 (HO-1), and various cytochrome P450 enzymes, whereas it
      enhanced expression of CD3, inducible nitric oxide synthase, and TNF alpha, as
      well as the total number of neutrophils in liver tissue. Spleens from co-treated
      animals contained large numbers of erythrocytes and neutrophils, but fewer CD3+
      cells, and demonstrated increased apoptosis in the white pulp. CONCLUSIONS:
      AMD3100 administration in a mouse model of endotoxemia further impaired health
      status and liver function and mediated pro-inflammatory, pro-oxidative, and pro
      apoptotic effects. This suggests that interruption of the CXCR4/CXCL12 axis is
      deleterious in acute inflammation and confirms previous findings showing
      beneficial effects of CXCR4 agonists in endotoxemia, thereby more clearly
      elucidating the role of CXCR4 in inflammation.

PMID- 27716215
TI  - Kinematic real-time feedback is more effective than traditional teaching method
      in learning ankle joint mobilisation: a randomised controlled trial.
AB  - BACKGROUND: To analyse the effect of real-time kinematic feedback (KRTF) when
      learning two ankle joint mobilisation techniques comparing the results with the
      traditional teaching method. METHODS: Double-blind randomized trial. SETTINGS:
      Faculty of Health Sciences. PARTICIPANTS: undergraduate students with no
      experience in manual therapy. Each student practised intensely for 90 min (45 min
      for each mobilisation) according to the random methodology assigned (G1:
      traditional method group and G2: KRTF group). G1: an expert professor supervising
      the student's practice, the professorstudent ratio was 1:8. G2: placed in front
      of a station where, while they performed the manoeuvre, they received a KRTF on a
      laptop. OUTCOME MEASURES: total time of mobilisation, time to reach maximum
      amplitude, maximum angular displacement in the three axes, maximum and average
      velocity to reach the maximum angular displacement, average velocity during the
      mobilisation. RESULTS: Among the pre-post intervention measurements, there were
      significant differences within the two groups for all outcome variables, however,
      G2 (KRTF) achieved significantly greater improvements in kinematic parameters for
      the two mobilisations (significant increase in displacement, velocity and
      significant reduction in the mobilisations runtime) than G1. Ankle plantar
      flexion: G1's measurement stability (post-intervention) ranged between 0.491 and
      0.687, while G2's measurement stability ranged between 0.899 and 0.984. Ankle
      dorsal flexion mobilisation: G1 the measurement stability (post-intervention)
      ranged from 0.543 and 0.684 while G2 ranged between 0.899 and 0.974. CONCLUSION:
      KRTF was proven to be more effective tool than traditional teaching method in the
      teaching - learning process of two joint mobilisation techniques. TRIAL
      REGISTRATION: NCT02504710.

PMID- 27716216
TI  - The Anatomy to Genomics (ATG) Start Genetics medical school initiative:
      incorporating exome sequencing data from cadavers used for Anatomy instruction
      into the first year curriculum.
AB  - BACKGROUND: The increasing use of next generation DNA sequencing in clinical
      medicine is exposing the need for more genetics education in physician training.
      We piloted an initiative to determine the feasibility of incorporating exome
      sequencing data generated from DNA obtained from cadavers used for teaching
      Anatomy into a first year medical student integrated block-style course. METHODS:
      We optimized the procedure to obtain DNA for exome sequencing by comparing the
      quality and quantity of DNA isolated from several tissues by two different
      extraction methods. DNA was sequenced using exome capture and analyzed using
      standard methods. Single nucleotide variants (SNVs), as well as small
      insertions/deletions, with potential functional impact were selected by faculty
      for student teams to independently investigate and prepare presentations on their
      findings. RESULTS: A total of seven cadaver DNAs were sequenced yielding high
      quality results. SNVs were identified that were associated, with known physical
      traits and disease susceptibility, as well as pharmacogenomic phenotypes.
      Students presented findings based on correlation with known clinical information
      about the cadavers' diseases and traits. CONCLUSION: Exome sequencing of cadaver
      DNA is a useful tool to integrate Anatomy with Genetics and Biochemistry into a
      first year medical student core curriculum.

PMID- 27716217
TI  - Ultrasound-guided gastrocnemius recession: a new ultra-minimally invasive
      surgical technique.
AB  - BACKGROUND: Isolated gastrocnemius contracture is thought to lead to numerous
      conditions. Although many techniques have been described for gastrocnemius
      recession, potential anesthetic, cosmetic, and wound-related complications can
      lead to patient dissatisfaction. Open and endoscopic recession techniques require
      epidural anesthesia, lower limb ischemia, and stitches and may lead to damage of
      the sural nerve, which is not under the complete control of the surgeon at all
      stages of the procedure. The purpose of this study was to evaluate the safety and
      efficacy of a new technique based on ultrasound-guided ultra-minimally invasive
      gastrocnemius recession. METHODS: We performed a pilot study with 22 cadavers to
      ensure that the technique was effective and safe. In the second phase, we
      prospectively performed gastrocnemius recession in 23 patients (25 cases) with
      chronic non-insertional Achilles tendinopathy, equinus foot, and other
      indications. In the clinical study, we evaluated the range of dorsiflexion before
      and after the procedure, clinical outcomes with VAS and AOFAS scores, and
      potential complications, including neurovascular injuries. RESULTS: We achieved
      complete release of the gastrocnemius tendon in all cases in the cadaveric study,
      with no damage to the sural nerve or vessels and minimal damage to the underlying
      muscle fibers. Ankle dorsiflexion increased for every patient in the study (mean,
      14 degrees ; standard deviation, 3 degrees ) and was maintained throughout follow
      up. The mean preoperative VAS score was 7 (6-9), which improved to 0 (0-1). The
      AOFAS Ankle-Hindfoot Score improved from a mean of 30 (20-40) to 93 (85-100) at 6
      months. No major complications were observed. All patients returned to their
      previous sports after 6 months. CONCLUSIONS: After cadaveric and clinical study,
      we considered the technique to be safe and effective to perform ultrasound-guided
      ultra-minimally invasive gastrocnemius recession using a 1-mm incision in vivo.
      This novel technique represents an alternative to open techniques, with
      encouraging results and with the advantages of reducing pain, obviating lower
      limb ischemia, deeper anaesthesia, thus decreasing complications and
      contraindications and accelerating recovery.

PMID- 27716218
TI  - Effectiveness of community-based football compared to usual care in men with
      prostate cancer: Protocol for a randomised, controlled, parallel group,
      multicenter superiority trial (The FC Prostate Community Trial).
AB  - BACKGROUND: Prostate cancer is the most common non-cutaneous malignancy in men.
      Today most patients may expect to live years following the diagnosis and may thus
      experience significant morbidity due to disease progression and treatment
      toxicity. In order to address some of these problems exercise has been suggested
      and previously studies have shown improvements of disease specific quality of
      life and a reduction in treatment-related toxicity. Cohort studies with long term
      follow up have suggested that physical activity is associated with improved
      survival in prostate cancer patients. Previously one randomised controlled trial
      has examined the efficacy of football in prostate cancer patients undergoing
      androgen deprivation therapy to usual care and reported positive effects on lean
      body mass and bone markers. Against this background, we wish to examine the
      effectiveness of community-based football for men diagnosed with prostate cancer.
      METHODS: Using a randomised controlled parallel group, multicenter, superiority
      trial design, two hundred prostate cancer patients will be recruited and
      randomised (1:1) to either community-based football one hour twice weekly or to a
      control group. The intervention period will be six months. The primary outcome is
      quality of life assessed after 12 weeks based on the change from baseline in the
      Functional Assessment of Cancer Therapy-Prostate questionnaire. Secondary
      outcomes are change from baseline to six months in quality of life, lean body
      mass, fat mass, whole body and regional bone markers, as well as physical
      activity and functional capacity at 12 weeks and six months. Safety outcome
      variables will be falls resulting in seeking medical assessment and fractures
      during the six-month period. DISCUSSION: Football is viewed as a case for non
      professional, supervised community-based team sport for promoting long-term
      physical activity in men diagnosed with prostate cancer. This randomised trial
      will provide data on effectiveness and safety for men with prostate cancer when
      football training is delivered in local football clubs. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT02430792.

PMID- 27716219
TI  - Effect of psycho-educational interventions on quality of life in patients with
      implantable cardioverter defibrillators: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Implantable cardioverter defibrillators (ICD) were developed for
      primary and secondary prevention of sudden cardiac death. However, ICD
      recipients' mortality is significantly predicted by their quality of life (QOL).
      The aim of this meta-analysis was to evaluate the effects of psycho-educational
      interventions on QOL in patients with ICDs. METHODS: We systematically searched
      PubMed, Medline, Cochrane Library, and CINAHL through April 2015 and references
      of relevant articles. Studies were reviewed if they met following criteria: (1)
      randomized controlled trial, (2) participants were adults with an ICD, and (3)
      data were sufficient to evaluate the effect of psychological or educational
      interventions on QOL measured by the SF-36 or SF-12. Studies were independently
      selected and their data were extracted by two reviewers. Study quality was
      evaluated using a modified Jadad scale. The meta-analysis was conducted using the
      Cochrane Collaboration's Review Manager Software Package (RevMan 5). Study
      heterogeneity was assessed by Q statistics and I 2 statistic. Depending on
      heterogeneity, data were pooled across trials using fixed-effect or random-effect
      modeling. RESULTS: Seven randomized controlled trials fulfilled the inclusion and
      exclusion criteria, and included 1017 participants. The psycho-educational
      interventions improved physical component summary (PCS) scores in the
      intervention groups more than in control groups (mean difference 2.08, 95 % CI
      0.86 to 3.29, p < 0.001), but did not significantly affect mental component
      summary (MCS) scores (mean difference 0.84, 95 % CI -1.68 to 3.35, p = 0.52).
      CONCLUSION: Our meta-analysis demonstrates that psycho-educational interventions
      improved the physical component, but not the mental component of QOL in patients
      with ICDs.

PMID- 27716220
TI  - The APOA5 rs662799 polymorphism is associated with dyslipidemia and the severity
      of coronary heart disease in Chinese women.
AB  - BACKGROUND: The APOA5 rs662799 polymorphism has been widely reported regarding
      its associations with the plasma lipid levels and the occurrence of coronary
      heart disease (CHD), whereas its relationship with the severity of CHD has not
      yet been explored. METHODS: Four hundred and seventy-eight angiografically
      defined subjects (325 CHD patients and 153 CHD-free controls) were enrolled in
      this study. The rs662799 polymorphism was genotyped, and the fasting lipid data
      were collected for all participants. The severity of CHD was evaluated for the
      CHD patients by using Gensini scores. RESULTS: The variant C allele of the
      rs662799 polymorphism was associated with lower levels of HDL-C in CHD-free
      women, and higher levels of TG and TG/HDL-C in women with CHD (P < 0.05 for all).
      The C allele was associated with higher prevalence of dyslipidemia and higher
      levels of Gensini scores only in women (P < 0.05 for both), but not in men.
      Multivariate linear regression analysis showed that the rs662799 polymorphism was
      independently associated with the Gensini scores in women after adjustment for
      other potential CHD risk factors (Beta = 0.157, 95 % CI: 0.017-0.298, P = 0.028).
      CONCLUSION: Our data indicate that the rs662799 polymorphism is associated with
      dyslipidemia and the severity of CHD in Chinese women.

PMID- 27716221
TI  - Self-management of musculoskeletal hand pain and hand problems in community
      dwelling adults aged 50 years and older: results from a cross-sectional study in
      a UK population.
AB  - BACKGROUND: Musculoskeletal pain is common in adults, with the hand being
      frequently affected. Healthcare services have the potential to be of benefit to
      adults with hand pain and problems, through promotion and facilitation of self
      management. METHODS: This paper explores existing self-management in a UK
      population of community-dwelling adults aged 50 years and over using data from
      surveys and a nested clinical cohort study. Self-management of hand problems was
      considered in three ways: self-directed treatment approaches used, adaptation
      behaviours adopted and choice to consult with a healthcare professional. RESULTS:
      The treatment approaches most commonly used were 'exercise/movement' (n = 151, 69
      %) and 'resting' the hands (n = 139, 69 %). The use of adaptation behaviour was
      widespread: 217 (99 %) people reported using one or more adaptation behaviours.
      Under half of survey respondents who reported hand pain (n = 783, 43 %) had
      consulted a healthcare professional about their problem during the last year: the
      lowest rate of consultation was for occupational therapy (n = 60, 3 %).
      CONCLUSIONS: Self-directed treatment and adaptation behaviours were widespread in
      adults aged 50 years and over with hand problems, but consultation with a
      healthcare professional was low.

PMID- 27716222
TI  - Complicated norovirus infection and assessment of severity by a modified Vesikari
      disease score system in hospitalized children.
AB  - BACKGROUND: Norovirus (NoV) GII.4 is the most common genotype for norovirus
      gastroenteritis worldwide. New variants or subgenotypes are continuously
      emerging, thus posing a serious threat to child health. METHODS: We compared
      retrospectively the clinical manifestations and complications of norovirus
      gastroenteritis in children from April, 2004 through December, 2012. NoV variants
      were analyzed to investigate the association of circulating viral strains with
      the complications. A modified disease severity score system based on Vesikari
      score system was devised and to evaluate disease severity. RESULTS: Compared to
      the outbreak in 2004/2005 winter, significant higher incidence of complications
      in the later periods are: convulsive disorder (p < 0.001) in 2006/2007 winter
      gastrointestinal hemorrhage (p = 0.047) and severe abdominal pain or irritability
      (p = 0.033) in 2008/09/10 winter; gastrointestinal hemorrhage (p = 0.030), severe
      abdominal pain or irritability (p = 0.014), and prominent hyperthermia (fever >39
      degrees C, p = 0.001) in 2011/2012 winter. GII.4 Den_Haag_2006b, GII.4 2010,
      GII.4 Sydney 2012, and GII.4 2012b were the predominant strains in the outbreaks
      after 2006. By the modified severity score system, severe norovirus disease
      occurred in 28.5 %, 32 %, 33.3 %, and 30.2 % of the patients in the four periods.
      A longer duration of hospitalization (p = 0.02) were found in those with high
      score irrespective of the year of admission. CONCLUSIONS: Our study demonstrated
      NoV outbreaks in northern Taiwan caused by different GII.4 variants that were
      associated with specific complications and uncommon clinical presentations. A
      modified severity score system first proposed in this study was able to identify
      severe cases with a longer hospital stay in NoV-infected children.

PMID- 27716223
TI  - Gender difference and effect of pharmacotherapy: findings from a smoking
      cessation service.
AB  - BACKGROUND: Smoking cessation services are available in England to provide
      assistance to those wishing to quit smoking. Data from one such service were
      analysed in order to investigate differences in quit rate between males and
      females prescribed with different treatments. METHODS: A logistic regression
      model was fitted to the data using the binary response of self-reported quit
      (failed attempt = 0, successful attempt = 1), validated by Carbon Monoxide (CO)
      monitoring, 4 weeks after commencing programme. Main effects fitted were: client
      gender; age; region; the type of advisory sessions; and pharmacotherapy, Nicotine
      Replacement Therapy (NRT) or Varenicline. A second model was fitted including all
      main effects plus two-way interactions except region. These models were repeated
      using 12-week self-reported quit as the outcome. RESULTS: At 4 weeks, all main
      effects were statistically significant, with males more likely (odds ratio and 95
      % CI, females v males = 0.88 [0.79-0.97]), older smokers more likely (adjusted
      odds ratios [OR] and 95 % confidence interval [CI] respectively for groups 20-29,
      30-49, 50-69 and 70+ vs 12-19 age group: 1.79 [1.39-2.31], 2.12 [1.68-2.68], 2.30
      [1.80-2.92] and 2.47 [1.81-3.37] and for overall difference between groups,
      chi2(4) = 53.5, p < 0.001) and clients being treated with Varenicline more likely
      to have successfully quit than those on NRT (adjusted OR and 95 % CI for
      Varenicline vs NRT = 1.41 [1.21-1.64]). Statistically significant interactions
      were observed between (i) gender and type of counselling, and (ii) age and type
      of counselling. Similar results were seen in relation to main effects at 12 weeks
      except that type of counselling was non-significant. The only significant
      interaction at this stage was between gender and pharmacotherapy (adjusted OR and
      95 % CI for females using Varenicline versus all other groups = 1.43 [1.06
      1.94]). CONCLUSION: Gender and treatment options were identified as predictors of
      abstinence at both 4 and 12 weeks after quitting smoking. Furthermore,
      interactions were observed between gender and (i) type of counselling received
      (ii) pharmacotherapy. In particular, the quit rate in women at 12 weeks was
      significantly improved in conjunction with Varenicline use. These findings have
      implications for service delivery.

PMID- 27716224
TI  - Factors associated with acceptability of child circumcision in Botswana -- a
      cross sectional survey.
AB  - BACKGROUND: Safe male child circumcision has been recently adopted as a potential
      strategy to prevent HIV/AIDS transmission in later life in Botswana. METHODS:
      Data used was derived from a cross-sectional survey, the Botswana AIDS Impact
      Survey (BAIS) IV, conducted in 2013. A total sample of 7984 respondents in ages
      15-64 years who had successfully completed the individual questionnaire during
      the survey were selected and included for analysis. Both descriptive and
      multivariable analyses were used to explore factors associated with acceptability
      of child circumcision. Data was analysed using SPSS version 22 program. RESULTS:
      Results indicate that about 84 % of participants said they would circumcise their
      male children aged 18 years and below, while 93 % were aware of the safe male
      circumcision program. Bivariate analyses results show that acceptability of child
      circumcision was significantly associated with sex, age, education, religion,
      residence, HIV status of the parent, fathers circumcision status, father's
      intention to circumcise and parent's knowledge about the safe male circumcision
      program. Multivariable analyses results indicate positive association between
      respondent's HIV positive status (OR, 3.5), Men's circumcision status (OR, 3.7),
      men's intention to circumcise (OR, 9.3) and acceptability of child circumcision.
      CONCLUSION: Results of this study indicate some relatively high acceptability
      levels for child circumcision. Some individual behavioural factors influencing
      acceptability of child circumcision were also identified. This study provides a
      proper understanding of factors associated with acceptability of child
      circumcision which will ultimately enhance the successful roll-out of the school
      going children circumcision program in Botswana.

PMID- 27716225
TI  - Functional inclusion bodies produced in the yeast Pichia pastoris.
AB  - BACKGROUND: Bacterial inclusion bodies (IBs) are non-toxic protein aggregates
      commonly produced in recombinant bacteria. They are formed by a mixture of highly
      stable amyloid-like fibrils and releasable protein species with a significant
      extent of secondary structure, and are often functional. As nano structured
      materials, they are gaining biomedical interest because of the combination of
      submicron size, mechanical stability and biological activity, together with their
      ability to interact with mammalian cell membranes for subsequent cell penetration
      in absence of toxicity. Since essentially any protein species can be obtained as
      IBs, these entities, as well as related protein clusters (e.g., aggresomes), are
      being explored in biocatalysis and in biomedicine as mechanically stable sources
      of functional protein. One of the major bottlenecks for uses of IBs in biological
      interfaces is their potential contamination with endotoxins from producing
      bacteria. RESULTS: To overcome this hurdle, we have explored here the controlled
      production of functional IBs in the yeast Pichia pastoris (Komagataella spp.), an
      endotoxin-free host system for recombinant protein production, and determined the
      main physicochemical and biological traits of these materials. Quantitative and
      qualitative approaches clearly indicate the formation of IBs inside yeast,
      similar in morphology, size and biological activity to those produced in E. coli,
      that once purified, interact with mammalian cell membranes and penetrate cultured
      mammalian cells in absence of toxicity. CONCLUSIONS: Structurally and
      functionally similar from those produced in E. coli, the controlled production of
      IBs in P. pastoris demonstrates that yeasts can be used as convenient platforms
      for the biological fabrication of self-organizing protein materials in absence of
      potential endotoxin contamination and with additional advantages regarding, among
      others, post-translational modifications often required for protein
      functionality.

PMID- 27716227
TI  - Modified mallampati classification in determining the success of unsedated
      transesophageal echocardiography procedure in patients with heart disease: simple
      but efficient.
AB  - BACKGROUND: The transesophageal echocardiograhpy (TEE) has been studied
      worldwide. However, identifying additional factors on top of operator's
      experience and patient's cooperation which could influence the success of the
      procedure in unsedated patients with heart disease  is not well documented.
      METHODS: Under the cross-sectional descriptive design, 85 target patients were
      fulfilling the criteria: being Thai national at the age of at least 20-year-old,
      being performed TEE by the study participant's cardiologists, being able to
      communicate verbally. Seven outcomes were recorded, including gag reflex,
      insertion attempt, insertion time, vital signs (heart rate, oxygen saturation and
      mean arterial blood pressure), visible blood on TEE probe tip, and oropharyngeal
      pain at 1 h and 24-h. RESULTS: There were 85 eligible patients during June 2013
      to June 2014 [corrected]. The major participants were male (46, 54 %) and the
      mean age was 51.2 +/- 12.5 years. The MMC class III was mostly found (33, 38.80
      %). TEE probe insertion time and gag reflex were indicated statistical
      significance (P < 0.05). Linear regression revealed that MMC class III (b 3.718;
      SD +/- 1.077; P = 0.001) and class IV (b 5.15; SD +/- 1.286; P = 0.000) were
      statistically associated with TEE probe insertion time, whereas MMC class II was
      no statistically significant (b 2.348; SD +/- 1.405; P = 0.099) according to
      constant value in MMC class I (5.318 s). Similarly, logistic regression indicated
      that the patients with high grade MMC were more likely to have gagging than the
      low grade MMC patients (MMC 2 OR 0.567, 95 % CI 0.09-3.42, P = 0.536; MMC 3 OR
      5.231, 95 % CI 1.55-17.67, P = 0.008; MMC 4 OR 3.4, 95 % CI 0.84-13.76, P =
      0.086). CONCLUSIONS: Modified Mallampati Classification is one of determining
      factors in the success of unsedated TEE procedure in patients with heart disease,
      especially for assessment of gagging and successful TEE probe insertion time.

PMID- 27716226
TI  - A pilot cluster randomised controlled trial of a support and training
      intervention to improve the mental health of secondary school teachers and
      students - the WISE (Wellbeing in Secondary Education) study.
AB  - BACKGROUND: Secondary school teachers are at heightened risk of psychological
      distress, which can lead to poor work performance, poor quality teacher-student
      relationships and mental illness. A pilot cluster randomised controlled trial
      (RCT) - the WISE study - evaluated the feasibility of a full-scale RCT of an
      intervention to support school staff's own mental health, and train them in
      supporting student mental health. METHODS: Six schools were randomised to an
      intervention or control group. In the intervention schools i) 8-9 staff received
      Mental Health First Aid (MHFA) training and became staff peer supporters, and ii)
      youth MHFA training was offered to the wider staff body. Control schools
      continued with usual practice. We used thematic qualitative data analysis and
      regression modelling to ascertain the feasibility, acceptability and potential
      usefulness of the intervention. RESULTS: Thirteen training observations, 14 staff
      focus groups and 6 staff interviews were completed, and 438 staff (43.5 %) and
      1,862 (56.3 %) students (years 8 and 9) completed questionnaires at baseline and
      one year later. MHFA training was considered relevant for schools, and trainees
      gained in knowledge, confidence in helping others, and awareness regarding their
      own mental health. Suggestions for reducing the length of the training and
      focusing on helping strategies were made. A peer support service was established
      in all intervention schools and was perceived to be helpful in supporting
      individuals in difficulty - for example through listening, and signposting to
      other services - and raising the profile of mental health at a whole school
      level. Barriers to use included lack of knowledge about the service, concerns
      about confidentiality and a preference for accessing support from pre-existing
      networks. CONCLUSIONS: The WISE intervention is feasible and acceptable to
      schools. Results support the development of a full-scale cluster RCT, if steps
      are taken to improve response rates and implement the suggested improvements to
      the intervention. TRIAL REGISTRATION: International Standard Randomised
      Controlled Trial Number: ISRCTN13255300 retrospectively registered 28/09/16.

PMID- 27716228
TI  - Measuring the impact of migraine for evaluating outcomes of preventive treatments
      for migraine headaches.
AB  - BACKGROUND: Migraine is characterized by headache with symptoms such as intense
      pain, nausea, vomiting, photophobia, and phonophobia that significantly impact
      individuals' lives. The objective of this study was to develop a strategy to
      measure outcomes from the patients' perspectives for use in evaluating preventive
      treatments for migraine. METHODS: This study used a multi-stage process. The
      first stage included concept identification research through literature review,
      patient-reported outcome (PRO) instrument content review, and clinician
      interviews, and resulted in a list of concepts relevant to understand the
      migraine experience. These results informed the design of the subsequent concept
      elicitation stage that involved qualitative interviews of adults with migraine to
      understand their experiences. Information from these two stages was used to
      develop a conceptual disease model (CDM) of the migraine experience. This CDM was
      used to identify concepts of interest (COI) to evaluate patient-relevant outcomes
      for assessing treatment benefit of migraine prophylactics. In the final stage,
      existing PRO instruments were reviewed to assess coverage of concepts related to
      the selected COI. RESULTS: Nine articles from 563 screened abstracts underwent
      full review to identify migraine-relevant concepts. This concept identification
      and subsequent concept elicitation interviews (N = 32; 21 episodic migraine; 11
      chronic migraine) indicated that people with migraine experience difficulties
      during and between migraine attacks with considerable day-to-day variability in
      the impact on movement, ability to perform every day and social activities, and
      emotion. The CDM organized concepts as proximal to and more distal from disease
      defining migraine symptoms, and was used to identify impact on physical function
      as the key COI. The item level review of PRO instruments revealed that none of
      the existing PRO instruments were suitable to collect data on impact of migraine
      on physical functioning, to evaluate treatment benefit. CONCLUSIONS: The impact
      of migraine includes impairments in functioning during and between migraine
      attacks that vary considerably on a daily basis. There is a need for novel PRO
      instruments that reflect patients' migraine experience to assess treatment
      benefit of migraine prophylactics. These instruments must evaluate the concepts
      identified and be able to capture the variability of patients' experience.

PMID- 27716229
TI  - Particulate-steroid betamethasone added to ropivacaine in interscalene brachial
      plexus block for arthroscopic rotator cuff repair improves postoperative
      analgesia.
AB  - BACKGROUND: Dexamethasone added to local anesthetic for brachial plexus block
      improves postoperative pain after arthroscopic rotator cuff repair, as compared
      with the use of local anesthetic alone. Dexamethasone is present in non
      particulate form in local anesthetic solution, while betamethasone is partially
      present in particulate form. The particulate betamethasone gradually decays and
      is expected to cause its longer-lasting effect. This study investigated the
      postoperative analgesic effect of betamethasone added to ropivacaine for brachial
      plexus block in patients who underwent arthroscopic rotator cuff repair. METHODS:
      This was a prospective, randomized, triple-blind study of 44 patients undergoing
      arthroscopic rotator cuff repair surgery. Ultrasound-guided interscalene brachial
      plexus block, involving 20 mL of 0.375 % ropivacaine (group R) or 19 mL of 0.375
      % ropivacaine with 4 mg (1 mL) of betamethasone (group BR), was administered and
      surgery was performed under general anesthesia. After surgery, the pain score was
      recorded at 12 h after surgery, and on the first, second, and seventh
      postoperative day. Analgesia duration, offset time of motor block, frequency of
      rescue analgesic administration, postoperative nausea/vomiting, and sleep
      disturbance during the night after surgery were recorded. The numerical values
      were expressed as median [interquartile range]. P values < 0.05 were considered
      statistically significant. RESULTS: The duration of analgesia was significantly
      prolonged in group BR (group BR: 19.1 h [16.6, 20.9 h], group R: 13.3 h [11.6,
      16.5 h], p < 0.001). The pain scores at 12 h after surgery and on the first and
      seventh day after surgery were significantly lower in group BR than in group R.
      The duration of motor block was significantly prolonged in group BR. The
      frequency of rescue analgesic administration and the sleep disturbance rate were
      significantly lower in group BR. There was no difference in postoperative
      nausea/vomiting between the two groups. CONCLUSIONS: Betamethasone added to local
      anesthetic in interscalene brachial plexus block improved postoperative pain
      after arthroscopic rotator cuff repair, and betamethasone prolonged the duration
      of analgesia by almost 6 h. TRIAL REGISTRATION: University Hospital Medical
      Information Network Center Clinical Trials Registration System ( UMIN000012899 ).

PMID- 27716230
TI  - Building capacity for knowledge translation in occupational therapy: learning
      through participatory action research.
AB  - BACKGROUND: There has been widespread acknowledgement of the need to build
      capacity in knowledge translation however much of the existing work focuses on
      building capacity amongst researchers rather than with clinicians directly. This
      paper's aim is to describe a research project for developing a knowledge
      translation capacity building program for occupational therapy clinicians.
      METHODS: Participatory action research methods were used to both develop and
      evaluate the knowledge translation capacity-building program. Participants were
      occupational therapists from a large metropolitan hospital in Australia.
      Researchers and clinicians worked together to use the action cycle of the
      Knowledge to Action Framework to increase use of knowledge translation itself
      within the department in general, within their clinical teams, and to facilitate
      knowledge translation becoming part of the department's culture. Barriers and
      enablers to using knowledge translation were identified through a survey based on
      the Theoretical Domains Framework and through focus groups. Multiple
      interventions were used to develop a knowledge translation capacity-building
      program. RESULTS: Fifty-two occupational therapists participated initially, but
      only 20 across the first 18 months of the project. Barriers and enablers were
      identified across all domains of the Theoretical Domains Framework. Interventions
      selected to address these barriers or facilitate enablers were categorised into
      ten different categories: educational outreach; teams working on clinical
      knowledge translation case studies; identifying time blocks for knowledge
      translation; mentoring; leadership strategies; communication strategies;
      documentation and resources to support knowledge translation; funding a knowledge
      translation champion one day per week; setting goals for knowledge translation;
      and knowledge translation reporting strategies. Use of these strategies was, and
      continues to be monitored. Participants continue to be actively involved in
      learning and shaping the knowledge translation program across the department and
      within their specific clinical areas. CONCLUSION: To build capacity for knowledge
      translation, it is important to involve clinicians. The action cycle of the
      Knowledge to Action framework is a useful guide to introduce the knowledge
      translation process to clinicians. It may be used to engage the department as a
      whole, and facilitate the learning and application of knowledge translation
      within specific clinical areas. Research evaluating this knowledge translation
      program is being conducted.

PMID- 27716231
TI  - Display of a beta-mannanase and a chitosanase on the cell surface of
      Lactobacillus plantarum towards the development of whole-cell biocatalysts.
AB  - BACKGROUND: Lactobacillus plantarum is considered as a potential cell factory
      because of its GRAS (generally recognized as safe) status and long history of use
      in food applications. Its possible applications include in situ delivery of
      proteins to a host, based on its ability to persist at mucosal surfaces of the
      human intestine, and the production of food-related enzymes. By displaying
      different enzymes on the surface of L. plantarum cells these could be used as
      whole-cell biocatalysts for the production of oligosaccharides. In this present
      study, we aimed to express and display a mannanase and a chitosanase on the cell
      surface of L. plantarum. RESULTS: ManB, a mannanase from Bacillus licheniformis
      DSM13, and CsnA, a chitosanase from Bacillus subtilis ATCC 23857 were fused to
      different anchoring motifs of L. plantarum for covalent attachment to the cell
      surface, either via an N-terminal lipoprotein anchor (Lp_1261) or a C-terminal
      cell wall anchor (Lp_2578), and the resulting fusion proteins were expressed in
      L. plantarum WCFS1. The localization of the recombinant proteins on the bacterial
      cell surface was confirmed by flow cytometry and immunofluorescence microscopy.
      The highest mannanase and chitosanase activities obtained for displaying L.
      plantarum cells were 890 U and 1360 U g dry cell weight, respectively. In
      reactions with chitosan and galactomannans, L. plantarum CsnA- and ManB
      displaying cells produced chito- and manno-oligosaccharides, respectively, as
      analyzed by high performance anion exchange chromatography (HPAEC) and mass
      spectrometry (MS). Surface-displayed ManB is able to break down galactomannan
      (LBG) into smaller manno-oligosaccharides, which can support growth of L.
      plantarum. CONCLUSION: This study shows that mannanolytic and chitinolytic
      enzymes can be anchored to the cell surface of L. plantarum in active forms. L.
      plantarum chitosanase- and mannanase-displaying cells should be of interest for
      the production of potentially 'prebiotic' oligosaccharides. This approach, with
      the enzyme of interest being displayed on the cell surface of a food-grade
      organism, may also be applied in production processes relevant for food industry.

PMID- 27716232
TI  - The role of expression imbalance between adipose synthesis and storage mediated
      by PPAR-gamma/FSP27 in the formation of insulin resistance in catch up growth.
AB  - BACKGROUND: Catch up growth (CUG) motivated by under-nutrition can lead to
      insulin resistance (IR) and visceral fat over-accumulation. However, the precise
      mechanisms on IR induced by adipose tissue changes during CUG remain unresolved.
      METHODS: Experimental rats were divided into three groups: normal chow group,
      catch up growth group and resveratrol administrated group. The whole experiment
      was carried out in four stages: 4, 6, 8 and 12 weeks. Peroxisome-proliferator
      activated receptor gamma (PPAR-gamma) and fat-specific protein 27 (FSP27)
      expression level in epididymal adipose tissues (EAT) and subcutaneous adipose
      tissues (SAT) were detected along with other IR indicators. RESULTS: Calorie
      restriction (CR) significantly increased PPAR-gamma expression in EAT while
      decreased FSP27 expression. During re-feeding, both of the expression of PPAR
      gamma and FSP27 increased, even FSP27 returned to normal level when CUG for 4
      weeks. Although PPAR-gamma expression declined slightly at 8 weeks, it was still
      much stronger than normal chow groups. However, no changes were seen in SAT.
      Relative insufficiency of FSP27 expression in EAT results in a decrease in lipid
      storage capacity, causing a series of path physiological changes that led to the
      formation of IR. Resveratrol inhibited the expression of PPAR-gamma and promoted
      FSP27 expression, thus fundamentally improving IR. CONCLUSIONS: The imbalance
      between adipose synthesis and storage mediated by PPAR-gamma / FSP27 in the EAT
      plays a pivotal role in the formation of IR during CUG. Resveratrol can correct
      fat formation and storage imbalance status by up-regulating FSP27 and down
      regulating PPAR-gamma expression level, ameliorating insulin sensitivity.

PMID- 27716234
TI  - Erratum to: the effects of the DDS-1 strain of lactobacillus on symptomatic
      relief for lactose intolerance - a randomized, double-blind, placebo-controlled,
      crossover clinical trial.

PMID- 27716233
TI  - Age and HPV type as risk factors for HPV persistence after loop excision in
      patients with high grade cervical lesions: an observational study.
AB  - BACKGROUND: Persistent infections with high risk human papillomaviruses (HR-HPV)
      cause virtually all cervical cancers. METHODS: An observational study was
      conducted aiming to estimate the rate of HPV infection persistence after LEEP in
      patients with high grade squamous intraepithelial lesions (HSIL). Moreover, the
      study investigated if persistence is age related. For this reason a total of 110
      patients were included between January 2010 and June 2015. RESULTS: At 6 months
      after LEEP the overall HPV infection persistence rate was 40.9 %, at 12 months 20
      % and at 18 months 11.8 %. Type 16 showed the highest persistence rate: 27.3 % at
      6 months, 12.7 % at 12 months and 10 % at 18 months after LEEP. The persistence
      for HPV type 16 at 6 months after LEEP was significantly higher in the group >
      =36.5 years old compared to the persistence rate in the group <36.5 years old (p
      = 0.0027, RR = 2.75, 95 %epsilon(1.34; 5.64)) (see Table 3). CONCLUSIONS: LEEP
      does not completely eradicate HPV infection. HPV persistence rate after LEEP is
      higher in infections with type 16 and in women older than 36.5 years.

PMID- 27716236
TI  - Biased image cropping and non-independent samples.
AB  - Any figure in a research article will typically represent only a small portion of
      the total data gained by a researcher for that experiment, and it is therefore
      key that the figure accurately reflects what was found overall. Furthermore, if
      individual observations form clusters with differing mean properties, those
      individual observations would not represent independent samples from the
      populations being compared. In this example, the question of how to fairly
      represent and treat image data is addressed.

PMID- 27716235
TI  - Access to primary health care services for Indigenous peoples: A framework
      synthesis.
AB  - BACKGROUND: Indigenous peoples often find it difficult to access appropriate
      mainstream primary health care services. Securing access to primary health care
      services requires more than just services that are situated within easy reach.
      Ensuring the accessibility of health care for Indigenous peoples who are often
      faced with a vast array of additional barriers including experiences of
      discrimination and racism, can be complex. This framework synthesis aimed to
      identify issues that hindered Indigenous peoples from accessing primary health
      care and then explore how, if at all, these were addressed by Indigenous health
      care services. METHODS: To be included in this framework synthesis papers must
      have presented findings focused on access to (factors relating to Indigenous
      peoples, their families and their communities) or accessibility of Indigenous
      primary health care services. Findings were imported into NVivo and a framework
      analysis undertaken whereby findings were coded to and then thematically analysed
      using Levesque and colleague's accessibility framework. RESULTS: Issues relating
      to the cultural and social determinants of health such as unemployment and low
      levels of education influenced whether Indigenous patients, their families and
      communities were able to access health care. Indigenous health care services
      addressed these issues in a number of ways including the provision of transport
      to and from appointments, a reduction in health care costs for people on low
      incomes and close consultation with, if not the direct involvement of, community
      members in identifying and then addressing health care needs. CONCLUSIONS:
      Indigenous health care services appear to be best placed to overcome both the
      social and cultural determinants of health which hamper Indigenous peoples from
      accessing health care. Findings of this synthesis also suggest that Levesque and
      colleague's accessibility framework should be broadened to include factors
      related to the health care system such as funding.

PMID- 27716237
TI  - Grayscale inversion radiographic view provided improved intra- and inter-observer
      reliabilities in measuring spinopelvic parameters in asymptomatic adult
      population.
AB  - BACKGROUND: Recently, a grayscale inversion view was reported to improve intra-
      and inter-observer reliabilities in measuring coronal curvature with Cobb and
      pedicle methods in scoliosis patients. However, the grayscale transformation has
      never been applied to the measurements of spinopelvic parameters. The purpose of
      this study was to compare the measurement reliabilities of the spinoplevic
      sagittal parameters between the 'Standard View' and the 'Grayscale Inversion
      View' in normal adult populations. METHODS: A total of 30 asymptomatic subjects
      aged between 30 and 40 years were included in this study. Whole-spine
      posteroanterior radiographs were used to measure the spinoplevic sagittal
      parameters including thoracic kyphosis (TK), lumbar lordosis (LL), sagittal
      vertical axis (SVA), pelvic incidence (PI), sacral slope (SS) and pelvic tilt
      (PT) in both standard view and grayscale inversion view. Two independent
      observers measured the parameters twice at a 2-week interval. Intra- and inter
      observer reliabilities were compared between the two radiographic views. The
      absolute differences between the two sets of measurements on each view were
      calculated and compared. RESULTS: The intra-class correlation coefficients (ICCs)
      of PI, PT and SVA were greater in the grayscale inversion view than in the
      standard view (0.972 vs 0.817, 0.937 vs 0.833 and 0.964 vs 0.901 for observer 1,
      respectively; 0.990 vs 0.826, 0.995 vs 0.842 and 0.969 vs 0.919 for observer 2,
      respectively). Overall, the improvement of ICC was greater in parameters of
      sagittal pelvic alignment than in those of sagittal spinal alignment. As for the
      mean absolute differences between two measurements, significant differences
      existed between the two views in terms of PI, PT and SVA (p = 0.014, 0.016 and
      0.011 for observer 1, respectively; p = 0.014, 0.025 and 0.046 for observer 2,
      respectively). CONCLUSIONS: A grayscale inversion view provided improved intra-
      and inter-observer reliabilities in measuring spinoplevic alignment when compared
      with a standard view. This view was more useful in subjects whose pelvic
      anatomical structures can't be identified clearly on the standard X-ray view.

PMID- 27716238
TI  - International changes in end-of-life practices over time: a systematic review.
AB  - BACKGROUND: End-of-life policies are hotly debated in many countries, with
      international evidence frequently used to support or oppose legal reforms.
      Existing reviews are limited by their focus on specific practices or selected
      jurisdictions. The objective is to review international time trends in end-of
      life practices. METHODS: We conducted a systematic review of empirical studies on
      medical end-of-life practices, including treatment withdrawal, the use of drugs
      for symptom management, and the intentional use of lethal drugs. A search
      strategy was conducted in MEDLINE, EMBASE, Web of Science, Sociological
      Abstracts, PAIS International, Worldwide Political Science Abstracts,
      International Bibliography of the Social Sciences and CINAHL. We included studies
      that described physicians' actual practices and estimated annual frequency at the
      jurisdictional level. End-of-life practice frequencies were analyzed for
      variations over time, using logit regression. RESULTS: Among 8183 references, 39
      jurisdiction-wide surveys conducted between 1990 and 2010 were identified. Of
      those, 22 surveys used sufficiently similar research methods to allow further
      statistical analysis. Significant differences were found across surveys in the
      frequency of treatment withdrawal, use of opiates or sedatives and the
      intentional use of lethal drugs (X 2  > 1000, p < 0.001 for all). Regression
      analyses showed increased use of opiates and sedatives over time (p < 0.001),
      which could reflect more intense symptom management at the end of life, or
      increase in these drugs to intentionally cause patients' death. CONCLUSION: The
      use of opiates and sedatives appears to have significantly increased over time
      between 1990 and 2010. Better distinction between practices with different legal
      status is required to properly interpret the policy significance of these
      changes. Research on the effects of public policies should take a comprehensive
      look at trends in end-of-life practice patterns and their associations with
      policy changes.

PMID- 27716239
TI  - Minimally important difference of the Child Oral Health Impact Profile for
      children with orofacial anomalies.
AB  - BACKGROUND: The Child Oral Health Impact Profile (COHIP) is an instrument
      designed to measure the self-reported oral health-related quality of life of
      children between the ages of 8 and 15, including domains for oral health,
      functional well-being, social-emotional well-being, school environment and self
      image. The purpose of this study was to estimate the minimally important
      difference (MID) of the COHIP for patients with cleft lip/palate. METHODS: Data
      from a 6-year, prospective, longitudinal cohort study of children with cleft
      lip/palate were analyzed to estimate the MID. Analysis was restricted to patients
      with data at baseline and first follow-up and not receiving a surgical
      intervention in the intervening years (N = 281). MIDs were estimated via the
      anchor-based method, using the Global Assessment of Change, and the effect size
      distribution method. RESULTS: Based on the distributional method, the minimally
      important differences were 0.16 (oral health), 0.12 (functional), 0.22 (social
      emotional), 0.21 (school environment) and 0.19 (self-image). MID anchor estimates
      for COHIP domains ranged from -0.32 to 0.84. The anchor-based and effect size MID
      estimates for the overall COHIP score were 2.95 and 0.25, respectively.
      CONCLUSION: The minimally important difference of the Child Oral Health Impact
      Profile is recommended for interpreting clinically meaningful change in patients
      with cleft lip/palate.

PMID- 27716240
TI  - Salvage surgery for local failures after stereotactic ablative radiotherapy for
      early stage non-small cell lung cancer.
AB  - INTRODUCTION: The literature on surgical salvage, i.e. lung resections in
      patients who develop a local recurrence following stereotactic ablative
      radiotherapy (SABR), is limited. We describe our experience with salvage surgery
      in nine patients who developed a local recurrence following SABR for early stage
      non-small cell lung cancer (NSCLC). METHODS: Patients who underwent surgical
      salvage for a local recurrence following SABR for NSCLC were identified from two
      Dutch institutional databases. Complications were scored using the Dindo-Clavien
      classification. RESULTS: Nine patients who underwent surgery for a local
      recurrence were identified. Median time to local recurrence was 22 months.
      Recurrences were diagnosed with CT- and/or 18FDG-PET-imaging, with four patients
      also having a pre-surgical pathological diagnosis. Extensive adhesions were
      observed during two resections, requiring conversion from a thoracoscopic
      procedure to thoracotomy during one of these procedures. Three patients
      experienced complications post-surgery; grade 2 (N = 2) and grade 3a (N = 1),
      respectively. All resection specimens showed viable tumor cells. Median length of
      hospital stay was 8 days (range 5-15 days) and 30-day mortality was 0 %. Lymph
      node dissection revealed mediastinal metastases in 3 patients, all of whom
      received adjuvant therapy. CONCLUSIONS: Our experience with nine surgical
      procedures for local recurrences post-SABR revealed two grade IIIa complications,
      and a 30-day mortality of 0 %, suggesting that salvage surgery can be safely
      performed after SABR.

PMID- 27716241
TI  - The relationship between depression and overactive bladder/urinary incontinence
      symptoms in the clinical OAB population.
AB  - BACKGROUND: To investigate the relationship between depression and overactive
      bladder (OAB)/urinary incontinence symptoms among the clinical OAB population.
      METHODS: Patients who were diagnosed with overactive bladder (OAB) and age
      matched control subjects without OAB were enrolled. Depression symptoms were
      assessed using the Hospital Anxiety and Depression Scale (HADS-D).
      OAB/incontinence symptoms were assessed using the validated questionnaires: ICIQ
      UI, ICIQ-OAB, UDI-6, IIQ-7, and OAB-q. RESULTS: 27.5 % of OAB patients in our
      study had depression (HADS >=8), and 12 % of OAB patients had moderate to severe
      depression (HADS-D >=11). OAB patients reported significantly higher HADS-D
      depression scores compared to age-matched controls (5.3 +/- 3.9 versus 2.8 +/-
      3.9, p = 0.004). OAB patients with depression reported more severe incontinence
      symptoms (ICIQ-UI), greater bother and more impact on quality of life (UDI-6, IIQ
      7) compared to OAB patients without depression (p = 0.001, 0.01, <0.001,
      respectively). However there were no differences in ICIQ-OAB and OAB-q. Among OAB
      patients, there were positive correlations between the severity of depression
      symptoms and OAB/incontinence symptoms (p-values <0.001 to 0.035). CONCLUSIONS:
      27.5 % of OAB patients have depression. OAB patients with depression reported
      more severe urinary incontinence symptoms, greater bother and more impact on
      quality of life compared to those without depression. Future studies are needed
      to further examine the mechanistic links between depression and OAB/urinary
      incontinence.

PMID- 27716243
TI  - Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN):
      evolution of a content management system for point-of-care clinical decision
      support.
AB  - BACKGROUND: The Checklist for Early Recognition and Treatment of Acute Illness
      (CERTAIN) is an international collaborative project with the overall objective of
      standardizing the approach to the evaluation and treatment of critically ill
      patients world-wide, in accordance with best-practice principles. One of
      CERTAIN's key features is clinical decision support providing point-of-care
      information about common acute illness syndromes, procedures, and medications in
      an index card format. METHODS: This paper describes 1) the process of developing
      and validating the content for point-of-care decision support, and 2) the content
      management system that facilitates frequent peer-review and allows rapid updates
      of content across different platforms (CERTAIN software, mobile apps, pdf
      booklet) and different languages. RESULTS: Content was created based on survey
      results of acute care providers and validated using an open peer-review process.
      Over a 3 year period, CERTAIN content expanded to include 67 syndrome cards, 30
      procedure cards, and 117 medication cards. 127 (59 %) cards have been peer
      reviewed so far. Initially MS Word(r) and Dropbox(r) were used to create, store,
      and share content for peer-review. Recently Google Docs(r) was used to make the
      peer-review process more efficient. However, neither of these approaches met our
      security requirements nor has the capacity to instantly update the different
      CERTAIN platforms. CONCLUSION: Although we were able to successfully develop and
      validate a large inventory of clinical decision support cards in a short period
      of time, commercially available software solutions for content management are
      suboptimal. Novel custom solutions are necessary for efficient global point of
      care content system management.

PMID- 27716242
TI  - Zika Virus on a Spreading Spree: what we now know that was unknown in the 1950's.
AB  - Zika virus (ZIKV) is a mosquito-borne flavivirus that is transmitted through the
      bite of Aedes spp mosquitoes and less predominantly, through sexual intercourse.
      Prior to 2007, ZIKV was associated with only sporadic human infections with
      minimal or no clinical manifestations. Recently the virus has caused disease
      outbreaks from the Pacific Islands, the Americas, and off the coast of West
      Africa with approximately 1.62 million people suspected to be infected in more
      than 60 countries around the globe. The recent ZIKV outbreaks have been
      associated with guillain-barre syndrome, congenital syndrome (microcephaly,
      congenital central nervous system anomalies), miscarriages, and even death. This
      review summarizes the path of ZIKV outbreak within the last decade, highlights
      three novel modes of ZIKV transmission associated with recent outbreaks, and
      points to the hallmarks of congenital syndrome. The review concludes with a
      summary of challenges facing ZIKV research especially the control of ZIKV
      infection in the wake of most recent data showing that anti-dengue virus
      antibodies enhance ZIKV infection.

PMID- 27716244
TI  - Performance and time to become negative after treatment of three malaria rapid
      diagnostic tests in low and high malaria transmission settings.
AB  - BACKGROUND: The performance of different malaria rapid diagnostic tests (RDT) may
      be influenced by transmission intensity and by the length of time each test
      requires to become negative after treatment and patient's recovery. METHODS:
      Results of three RDTs (two HRP2 and one pLDH antigen-based tests) were compared
      to blood smear microscopy (the gold standard method) in children under 5 years of
      age living in a high versus low malaria intensity setting in southwestern Uganda.
      In each setting, 212 children, who tested positive by at least one RDT and by
      microscopy, were treated with artemether-lumefantrine. RDTs and microscopy were
      then repeated at fixed intervals to estimate each test's time to negativity after
      treatment and patient recovery. RESULTS: In the two settings, sensitivities
      ranged from 98.4 to 99.2 % for the HRP2 tests and 94.7 to 96.1 % for the pLDH
      test. Specificities were 98.9 and 98.8 % for the HRP2 tests and 99.7 % for the
      pLDH test in the low-transmission setting and 79.7, 80.7 and 93.9 %,
      respectively, in the high-transmission setting. Median time to become negative
      was 35-42 or more days for the HRP2 tests and 2 days for the pLDH test.
      CONCLUSIONS: High transmission contexts and a long time to become negative
      resulted in considerably reduced specificities for the HRP2 tests. Choice of RDT
      for low- versus high-transmission settings should balance risks and benefits of
      over-treatment versus missing malaria cases. TRIAL REGISTRATION: Registry number
      at ClinicalTrial.gov: NCT01325974.

PMID- 27716245
TI  - Research for Policy (R4P): development of a reflection tool for researchers to
      improve knowledge utilization.
AB  - BACKGROUND: To improve knowledge utilization in policymaking, alignment between
      researchers and policymakers during knowledge production is essential, but
      difficult to maintain. In three previously reported case studies, we extensively
      evaluated complex research projects commissioned by policymakers to investigate
      how alignment is achieved in a research process and to discover ways to enhance
      knowledge contributions to health policy. In the present study, we investigated
      how the findings of these three research projects could be integrated into a
      practical tool for researchers to enhance their contribution to evidence-based
      policy. METHODS: A cross-case analysis was conducted to integrate the findings of
      the evaluation of the three research projects and to identify important alignment
      areas in these projects. By means of an iterative process, we prepared a tool
      that includes reflection questions for researchers. The "Research for Policy"
      tool was tested with input from the project managers of three new research
      projects. Based on the findings, the final version of the Research for Policy
      tool was prepared. RESULTS: By cross-case analysis of the three case studies, the
      following important alignment areas were identified: the goal, quality,
      relevance, timing, and presentation of research, the tasks and authorities of
      actors, the consultative structure and vertical alignment within organizations,
      and the organizational environment. The project managers regarded the Research
      for Policy tool as a useful checklist for addressing the important alignment
      areas in a research project. Based on their feedback, the illustrative examples
      from the case studies were added to the reflection questions. The project
      managers suggested making the tool accessible not only to researchers but also to
      policymakers. The format of the Research for Policy tool was further adjusted to
      users' needs by adding clickable links. CONCLUSIONS: Alignment between research
      and policymaking requires continuous efforts and a clear understanding of process
      issues in the research project. The Research for Policy tool offers practical
      alignment guidance and facilitates reflection on process issues, which supports
      researchers in aligning with policymakers and in acting in a context-sensitive
      way.

PMID- 27716246
TI  - Effects of coenzyme Q10 supplementation on antioxidant capacity and inflammation
      in hepatocellular carcinoma patients after surgery: a randomized, placebo
      controlled trial.
AB  - BACKGROUND: It has been reported that higher levels of oxidative stress and
      inflammation play a key role in the progression of hepatocellular carcinoma (HCC)
      after surgery. Coenzyme Q10 is an endogenous lipid-soluble antioxidant. To date,
      no intervention study has investigated coenzyme Q10 supplementation in HCC
      patients after surgery. The purpose of this study was to investigate oxidative
      stress, antioxidant enzymes activity, and inflammation levels in HCC patients
      after surgery following administration of coenzyme Q10 (300 mg/day). METHODS:
      This study was designed as a single-blinded, randomized, parallel, placebo
      controlled study. Patients who were diagnosed with primary HCC (n = 41) and were
      randomly assign to a placebo (n = 20) or coenzyme Q10 (300 mg/day, n = 21) group
      after surgery. The intervention lasted for 12 weeks. Plasma coenzyme Q10, vitamin
      E, oxidative stress antioxidant enzymes activity and inflammatory markers levels
      were measured. RESULTS: The oxidative stress (p = 0.04) and inflammatory markers
      (hs-CRP and IL-6, p < 0.01) levels were significantly decreased, and the
      antioxidant enzymes activity was significantly increased (p < 0.01) after 12
      weeks of coenzyme Q10 supplementation. In addition, the coenzyme Q10 level was
      significantly negatively correlated with the oxidative stress (p = 0.01), and
      positively correlated with antioxidant enzymes activity (SOD, p = 0.01; CAT, p <
      0.05; GPx, p = 0.04) and vitamin E level (p = 0.01) after supplementation.
      CONCLUSION: In conclusion, we demonstrated that a dose of 300 mg/d of coenzyme
      Q10 supplementation significantly increased the antioxidant capacity and reduced
      the oxidative stress and inflammation levels in HCC patients after surgery. TRIAL
      REGISTRATION: Clinical Trials.gov Identifier: NCT01964001.

PMID- 27716247
TI  - Mechanisms of action of an implementation intervention in stroke rehabilitation:
      a qualitative interview study.
AB  - BACKGROUND: Despite best evidence demonstrating the effectiveness of increased
      intensity of exercise after stroke, current levels of therapy continue to be
      below those required to optimise motor recovery. We developed and tested an
      implementation intervention that aims to increase arm exercise in stroke
      rehabilitation. The aim of this study was to illustrate the use of a behaviour
      change framework, the Behaviour Change Wheel, to identify the mechanisms of
      action that explain how the intervention produced change. METHODS: We implemented
      the intervention at three stroke rehabilitation units in the United Kingdom. A
      purposive sample of therapy team members were recruited to participate in semi
      structured interviews to explore their perceptions of how the intervention
      produced change at their work place. Audio recordings were transcribed and
      imported into NVivo 10 for content analysis. Two coders separately analysed the
      transcripts and coded emergent mechanisms. Mechanisms were categorised using the
      Theoretical Domains Framework (TDF) (an extension of the Capability, Opportunity,
      Motivation and Behaviour model (COM-B) at the hub of the Behaviour Change Wheel).
      RESULTS: We identified five main mechanisms of action: 'social/professional role
      and identity', 'intentions', 'reinforcement', 'behavioural regulation' and
      'beliefs about consequences'. At the outset, participants viewed the research
      team as an external influence for whom they endeavoured to complete the study
      activities. The study design, with a focus on implementation in real world
      settings, influenced participants' intentions to implement the intervention
      components. Monthly meetings between the research and therapy teams were central
      to the intervention and acted as prompt or reminder to sustain implementation.
      The phased approach to introducing and implementing intervention components
      influenced participants' beliefs about the feasibility of implementation.
      CONCLUSIONS: The Behaviour Change Wheel, and in particular the Theoretical
      Domains Framework, were used to investigate mechanisms of action of an
      implementation intervention. This approach allowed for consideration of a range
      of possible mechanisms, and allowed us to categorise these mechanisms using an
      established behaviour change framework. Identification of the mechanisms of
      action, following testing of the intervention in a number of settings, has
      resulted in a refined and more robust intervention programme theory for future
      testing.

PMID- 27716248
TI  - Instantaneous phase difference analysis between thoracic and abdominal movement
      signals based on complementary ensemble empirical mode decomposition.
AB  - BACKGROUND: Thoracoabdominal asynchrony is often adopted to discriminate
      respiratory diseases in clinics. Conventionally, Lissajous figure analysis is the
      most frequently used estimation of the phase difference in thoracoabdominal
      asynchrony. However, the temporal resolution of the produced results is low and
      the estimation error increases when the signals are not sinusoidal. Other
      previous studies have reported time-domain procedures with the use of band-pass
      filters for phase-angle estimation. Nevertheless, the band-pass filters need
      calibration for phase delay elimination. METHODS: To improve the estimation, we
      propose a novel method (named as instantaneous phase difference) that is based on
      complementary ensemble empirical mode decomposition for estimating the
      instantaneous phase relation between measured thoracic wall movement and
      abdominal wall movement. To validate the proposed method, experiments on
      simulated time series and human-subject respiratory data with two breathing types
      (i.e., thoracic breathing and abdominal breathing) were conducted. Latest version
      of Lissajous figure analysis and automatic phase estimation procedure were
      compared. RESULTS: The simulation results show that the standard deviations of
      the proposed method were lower than those of two other conventional methods. The
      proposed method performed more accurately than the two conventional methods. For
      the human-subject respiratory data, the results of the proposed method are in
      line with those in the literature, and the correlation analysis result reveals
      that they were positively correlated with the results generated by the two
      conventional methods. Furthermore, the standard deviation of the proposed method
      was also the smallest. CONCLUSIONS: To summarize, this study proposes a novel
      method for estimating instantaneous phase differences. According to the findings
      from both the simulation and human-subject data, our approach was demonstrated to
      be effective. The method offers the following advantages: (1) improves the
      temporal resolution, (2) does not introduce a phase delay, (3) works with non
      sinusoidal signals, (4) provides quantitative phase estimation without estimating
      the embedded frequency of breathing signals, and (5) works without calibrated
      measurements. The results demonstrate a higher temporal resolution of the phase
      difference estimation for the evaluation of thoracoabdominal asynchrony.

PMID- 27716249
TI  - Erratum to: An oral health optimized diet can reduce gingival and periodontal
      inflammation in humans - a randomized controlled pilot study.

PMID- 27716250
TI  - The impact of reimbursement systems on equity in access and quality of primary
      care: A systematic literature review.
AB  - BACKGROUND: Reimbursement systems provide incentives to health care providers and
      may drive physician behaviour. This review assesses the impact of reimbursement
      system on socioeconomic and racial inequalities in access, utilization and
      quality of primary care. METHODS: A systematic search was performed in Web of
      Science and PubMed for English language studies published between 1980 and 2013,
      supplemented by reference tracking. Articles were selected based on inclusion
      criteria, and data extraction and critical appraisal were performed by two
      authors independently. Data were synthesized in a narrative manner and
      categorized according to study outcome and reimbursement system. RESULTS: Twenty
      seven articles, mostly from the United States and United Kingdom, were included
      in the data synthesis. Reimbursement systems seem to have limited effect on
      socioeconomic and racial inequity in access, utilization and quality of primary
      care. Capitation might have a more beneficial impact on inequity in access to
      primary care and number of ambulatory care sensitive admissions than fee-for
      service, but did worse in patient satisfaction. Pay-for-performance had little or
      no impact on socioeconomic and racial inequity in the management of diabetes,
      cardiovascular diseases, chronic obstructive pulmonary disease, and preventive
      services. CONCLUSION: We found little scientific evidence supporting an
      association between reimbursement system and socioeconomic or racial inequity in
      access, utilization and quality of primary care. Overall, few studies addressed
      this research question, and heterogeneity in context and outcomes complicates
      comparisons across studies. Further empirical studies are warranted.

PMID- 27716251
TI  - Seroprevalence of human immunodeficiency virus, hepatitis B and C viruses, and
      Treponema pallidum infections among blood donors at Shiyan, Central China.
AB  - BACKGROUND: Ordinary screening of transfusion-transmissible infections (TTIs)
      among blood donors is essential for blood transfusion. Although there is several
      TTIs studies focus on human immunodeficiency virus, hepatitis B and C viruses,
      and Treponema pallidum infections in China, it is no data to illustrate any firm
      conclusion from Shiyan City, Central China. It aims to verify the seroprevalence
      of TTIs among blood donors at Shiyan. METHODS: A retrospective analysis of blood
      donors' information was conducted for the presence of HIV, HBV, HCV and T.
      pallidum. Logistic regression analysis was used to demonstrate risk factors
      including age, gender and occupation associated with them. The variation tendency
      in seroprevalence of these TTIs over the study period was evaluated by Cochran
      Armitage trend test. RESULTS: Of 211 639 blood donors, 2 858 (1.35 %) had
      serological evidence of TTIs. The seroprevalence of HIV, HBV, HCV and T. pallidum
      were 0.08 %, 0.51 %, 0.20 % and 0.57 %, respectively. However, the co-infection
      prevalence of TTIs has not been detected. The HIV seropositivity significantly
      increased among female donors (OR = 1.63, P < 0.001) and farmers (OR = 2.02, P =
      0.020). Significantly increased HBV seropositivity was only observed framers (OR
      = 1.87, P <0.001) compared to workers. Analogously, significantly increased HCV
      seropositivity was observed among farmers (OR = 2.59, P < 0.001), students (OR =
      2.43, P < 0.001), merchants (OR = 1.70, P = 0.014) and others (OR = 1.78, P
      =0.001). The T. pallidum seroprevalence was notably increased among female (OR =
      1.54, P < 0.001), and farmers (OR = 1.70, P <0.001). Moreover, significantly
      increasing trends of HIV (Z = -6.88, P < 0.01), HBV (Z = -4.52, P < 0.01), HCV (Z
      = -4.16, P < 0.01) and T. pallidum (Z = -1.36, P < 0.01) seropositivity were
      observed over the study period. CONCLUSIONS: It originally offers a substantial
      prevalence of TTIs among blood donors at Shiyan, Central China. Severe blood
      donor selection and all-inclusive screening of blood are highly recommended. It
      might be helpful for developing and updating guidance for blood safety. TRIAL
      REGISTRATION: Retrospectively registered.

PMID- 27716252
TI  - Do countries rely on the World Health Organization for translating research
      findings into clinical guidelines? A case study.
AB  - BACKGROUND: The World Health Organization's (WHO) antiretroviral therapy (ART)
      guidelines have generally been adopted rapidly and with high fidelity by
      countries in sub-Saharan Africa. Thus far, however, WHO has not published
      specific guidance on nutritional care and support for (non-pregnant) adults
      living with HIV despite a solid evidence base for some interventions. This offers
      an opportunity for a case study on whether national clinical guidelines in sub
      Saharan Africa provide concrete recommendations in the face of limited guidance
      by WHO. This study, therefore, aims to determine if national HIV treatment
      guidelines in sub-Saharan Africa contain specific guidance on nutritional care
      and support for non-pregnant adults living with HIV. METHODS: We identified the
      most recent national HIV treatment guidelines in sub-Saharan African countries
      with English as an official language. Using pre-specified criteria, we determined
      for each guideline whether it provides guidance to clinicians on each of five
      components of nutritional care and support for adults living with HIV: assessment
      of nutritional status, dietary counseling, micronutrient supplementation, ready
      to-use therapeutic or supplementary foods, and food subsidies. RESULTS: We found
      that national HIV treatment guidelines in sub-Saharan Africa generally do not
      contain concrete recommendations on nutritional care and support for non-pregnant
      adults living with HIV. CONCLUSIONS: Given that decisions on nutritional care and
      support are inevitably being made at the clinician-patient level, and that
      clinicians have a relative disadvantage in systematically identifying,
      summarizing, and weighing up research evidence compared to WHO and national
      governments, there is a need for more specific clinical guidance. In our view,
      such guidance should at a minimum recommend daily micronutrient supplements for
      adults living with HIV who are in pre-ART stages, regular dietary counseling,
      periodic assessment of anthropometric status, and additional nutritional
      management of undernourished patients. More broadly, our findings suggest that
      countries in sub-Saharan Africa look to WHO for guidance in translating evidence
      into clinical guidelines. It is, thus, likely that the development of concrete
      recommendations by WHO on nutritional interventions for people living with HIV
      would lead to more specific guidelines at the country-level and, ultimately,
      better clinical decisions and treatment outcomes.

PMID- 27716253
TI  - Nurse-administered intravitreal injections of anti-VEGF: study protocol for
      noninferiority randomized controlled trial of safety, cost and patient
      satisfaction.
AB  - BACKGROUND: Intravitreal injections (IVI) of anti-vascular endothelial growth
      factor (anti-VEGF) now improve or stabilize visual acuity in a number of
      previously untreatable eye diseases, of which the main are age-related macular
      degeneration, retinal vein occlusion and diabetic macular edema. Most patients
      require multiple injections over lengthy periods of time and the prevalence of
      treatable conditions is increasing. Anti-VEGF IVI normally administered by
      physicians, therefore represent a considerable workload on ophthalmologic clinics
      and will continue to do so in the near future. Nurse-administered IVI may relieve
      this workload, but the safety, cost and patient satisfaction of such an extended
      role for nurses in ophthalmologic clinics has not earlier been investigated. To
      investigate these outcomes following independent anti-VEGF IVI by trained nurses,
      a noninferiority randomized controlled trial is being conducted. METHODS/DESIGN:
      Patients eligible for anti-VEGF treatment, minimum 304, are recruited and
      randomized to IVI administration by either trained nurses or physicians. The
      primary outcome is safety, measured by difference in mean change in visual acuity
      between the two groups during an observation period of 12 months. Secondary
      outcomes are incidence of ocular adverse events, cost per patient and patient
      satisfaction. DISCUSSION: This study protocol describes the design of the first
      randomized controlled trial of nurse-administered IVI of anti-VEGF. The study is
      designed to examine safety, cost and patient satisfaction during 12 months follow
      up. TRIAL REGISTRATION: ClinicalTrials.gov NCT02359149 . Registered February 4,
      2015.

PMID- 27716254
TI  - Learning to use a body-powered prosthesis: changes in functionality and
      kinematics.
AB  - BACKGROUND: Little is known about action-perception learning processes underlying
      prosthetic skills in body-powered prosthesis users. Body-powered prostheses are
      controlled through a harness connected by a cable that might provide for limited
      proprioceptive feedback. This study aims to test transfer of training basic tasks
      to functional tasks and to describe the changes over time in kinematics of basic
      tasks of novice body-powered prosthesis users. METHODS: Thirty able-bodied
      participants and 17 controls participated in the study, using a body-powered
      prosthetic simulator. Participants in the training group were divided over four
      groups and practiced during a 2-week-period either direct grasping, indirect
      grasping, fixation, or a combination of these tasks. Deformable objects with
      different compliances had to be manipulated while kinematic variables and grip
      force control were assessed. Functional performance was measured with the
      Southampton Hand Assessment Procedure (SHAP) prior to and after the training
      sessions, and after 2 weeks and 3 months retention. The control group only
      performed the SHAP tests. RESULTS: All four training groups and the control group
      improved on the SHAP, also after a period of non-use. Type of training had a
      small but significant influence on the improvements of the SHAP score. On a
      kinematic level movement times decreased and hook closing velocities increased
      over time. The indirect grasping group showed significantly shorter plateau times
      than the other training groups. Grip force control only improved a little over
      training. CONCLUSIONS: Training action-perception couplings of body-powered
      prosthesis in basic tasks transferred to functional tasks and this lasted after a
      period of non-use. During training movement times decreased and the indirect
      grasping group showed advantages. It is advisable to start body-powered training
      with indirect grasping tasks but also to practice hook-object orientations.

PMID- 27716255
TI  - Alterations in neuromuscular function in girls with generalized joint
      hypermobility.
AB  - BACKGROUND: Generalized Joint Hypermobility (GJH) is associated with increased
      risk of musculoskeletal joint pain. We investigated neuromuscular performance and
      muscle activation strategy. METHODS: Girls with GJH and non-GJH (NGJH) performed
      isometric knee flexions (90 degrees ,110 degrees ,130 degrees ), and extensions
      (90 degrees ) at 20 % Maximum Voluntary Contraction, and explosive isometric knee
      flexions while sitting. EMG was recorded from knee flexor and extensor muscles.
      RESULTS: Early rate of torque development was 53 % faster for GJH. Reduced
      hamstring muscle activation in girls with GJH was found while knee extensor and
      calf muscle activation did not differ between groups. Flexion-extension and
      medial-lateral co-activation ratio during flexions were higher for girls with GJH
      than NGJH girls. CONCLUSIONS: Girls with GJH had higher capacity to rapidly
      generate force than NGJH girls which may reflect motor adaptation to compensate
      for hypermobility. Higher medial muscle activation indicated higher levels of
      medial knee joint compression in girls with GJH. Increased flexion-extension co
      activation ratios in GJH were explained by decreased agonist drive to the
      hamstrings.

PMID- 27716256
TI  - Use of email, cell phone and text message between patients and primary-care
      physicians: cross-sectional study in a French-speaking part of Switzerland.
AB  - BACKGROUND: Physicians' daily work is increasingly affected by the use of emails,
      text messages and cell phone calls with their patients. The aim of this study was
      to describe their use between primary-care physicians and patients in a French
      speaking part of Switzerland. METHODS: A cross-sectional mail survey was
      conducted among all primary-care physicians of Geneva canton (n = 636). The
      questionnaire focused on the frequency of giving access to, type of use,
      advantages and disadvantages of email, cell phone calls and text messages
      communication between physicians and patients. RESULTS: Six hundred thirty-six
      questionnaires were mailed, 412 (65 %) were returned and 372 (58 %) could be
      analysed (37 refusals and three blanks). Seventy-two percent physicians gave
      their email-address and 74 % their cell phone number to their patients. Emails
      were used to respond to patients' questions (82 %) and change appointments (72 %)
      while cell phone calls and text messages were used to follow patients' health
      conditions. Sixty-four percent of those who used email communication never
      discussed the rules for email exchanges, and 54 % did not address confidentiality
      issues with their patients. Most commonly identified advantages of emails, cell
      phone calls and text messages were improved relationship with the patient, saving
      time (for emails) and improving the follow-up (for cell phone and text messages).
      The main disadvantages included misuse by the patient, interference with private
      life and lack of reimbursement. CONCLUSIONS: These tools are widely used by
      primary-care physicians with their patients. More attention should be paid to
      confidentiality, documentation and reimbursement when using email communication
      in order to optimize its use.

PMID- 27716257
TI  - Characterization of virus-derived small interfering RNAs in Apple stem grooving
      virus-infected in vitro-cultured Pyrus pyrifolia shoot tips in response to high
      temperature treatment.
AB  - BACKGROUND: Heat treatment (known as thermotherapy) together with in vitro
      culture of shoot meristem tips is a commonly used technology to obtain virus-free
      germplasm for the effective control of virus diseases in fruit trees. RNA
      silencing as an antiviral defense mechanism has been implicated in this process.
      To understand if high temperature-mediated acceleration of the host antiviral
      gene silencing system in the meristem tip facilitates virus-derived small
      interfering RNAs (vsiRNA) accumulation to reduce the viral RNA titer in the fruit
      tree meristem tip cells, we used the Apple stem grooving virus (ASGV)-Pyrus
      pyrifolia pathosystem to explore the possible roles of vsiRNA in thermotherapy.
      RESULTS: At first we determined the full-length genome sequence of the ASGV-Js2
      isolate and then profiled vsiRNAs in the meristem tip of in vitro-grown pear (cv.
      'Jinshui no. 2') shoots infected by ASGV-Js2 and cultured at 24 and 37  degrees
      C. A total of 7,495 and 7,949 small RNA reads were obtained from the tips of pear
      shoots cultured at 24 and 37  degrees C, respectively. Mapping of the vsiRNAs to
      the ASGV-Js2 genome revealed that they were unevenly distributed along the ASGV
      Js2 genome, and that 21- and 22-nt vsiRNAs preferentially accumulated at both
      temperatures. The 5'-terminal nucleotides of ASGV-specific siRNAs in the tips
      cultured under different temperatures had a similar distribution pattern, and the
      nucleotide U was the most frequent. RT-qPCR analyses suggested that viral genome
      accumulation was drastically compromised at 37  degrees C compared to 24  degrees
      C, which was accompanied with the elevated levels of vsiRNAs at 37  degrees C. As
      plant Dicer-like proteins (DCLs), Argonaute proteins (AGOs), and RNA-dependent
      RNA polymerases (RDRs) are implicated in vsiRNA biogenesis, we also cloned the
      partial sequences of PpDCL2,4, PpAGO1,2,4 and PpRDR1 genes, and found their
      expression levels were up-regulated in the ASGV-infected pear shoots at 37 
      degrees C. CONCLUSIONS: Collectively, these results showed that upon high
      temperature treatment, the ASGV-infected meristem shoot tips up-regulated the
      expression of key genes in the RNA silencing pathway, induced the biogenesis of
      vsiRNAs and inhibited viral RNA accumulation. This study represents the first
      report on the characterization of the vsiRNA population in pear plants infected
      by ASGV-Js2, in response to high temperature treatment.

PMID- 27716258
TI  - Rifaximin is an effective alternative to metronidazole for the treatment of
      chronic enteropathy in dogs: a randomised trial.
AB  - BACKGROUND: A clinical trial was conducted in order to assess the efficacy of
      rifaximin, a broad-spectrum antibiotic with negligible gastrointestinal
      absorption, in comparison with metronidazole, a commonly employed antimicrobial
      drug, in dogs with chronic enteropathy. Twenty-four pet dogs were randomly
      enrolled into two different groups: MET group (10 dogs) and RIF group (14 dogs).
      Dogs of MET group received metronidazole 15 mg/kg q12h for 21 days by oral route,
      whereas dogs of RIF group, were given rifaximin 25 mg/kg q12h for 21 days by oral
      route. Clinical signs of disease were evaluated the day before the beginning of
      drug administration (D0), and at the end of treatment (D21), by means of Canine
      IBD Activity Index (CIBDAI). Blood levels of C-reactive protein (CRP) at D0 and
      D21 were also measured, as another parameter of treatment efficacy. The primary
      outcome measure of efficacy was the complete remission at D21, defined as a 75 %
      or greater decrease of CIBDAI; secondary outcome measures were the variation of
      mean CIBDAI scores, of mean CRP serum levels, and any observed adverse effect
      from D0 to D21. RESULTS: Treatment with metronidazole or rifaximin greatly
      improved the clinical signs of disease in each group: in MET group the complete
      remission was achieved in 8 of 10 dogs (80.0 %), and partial remission in 2
      subjects (20.0 %). In RIF group, 12 of 14 dogs showed complete remission (85.7
      %), and the remaining 2 dogs were in partial remission (14.3 %). There were also
      significant decreases of CIBDAI scores (P = 0.002 and P = 0.0002 for MET and RIF,
      respectively), and CRP levels (P = 0.002 and P = 0.0001 for MET and RIF,
      respectively) compared to pre-treatment values in both groups. No significant
      difference, however, was found when comparing MET and RIF groups. No relevant
      side-effect was reported during the trial with either drugs. CONCLUSIONS: The
      present study showed, for the first time, that oral rifaximin could represent an
      effective alternative to metronidazole for the induction of clinical remission in
      dogs with chronic enteropathy.

PMID- 27716259
TI  - Microarray data analysis to identify crucial genes regulated by CEBPB in human
      SNB19 glioma cells.
AB  - BACKGROUND: Glioma is one of the most common primary malignancies in the brain or
      spine. The transcription factor (TF) CCAAT/enhancer binding protein beta (CEBPB)
      is important for maintaining the tumor initiating capacity and invasion ability.
      To investigate the regulation mechanism of CEBPB in glioma, microarray data
      GSE47352 was analyzed. METHODS: GSE47352 was downloaded from Gene Expression
      Omnibus, including three samples of SNB19 human glioma cells transduced with non
      target control small hairpin RNA (shRNA) lentiviral vectors for 72 h (normal
      glioma cells) and three samples of SNB19 human glioma cells transduced with CEBPB
      shRNA lentiviral vectors for 72 h (CEBPB-silenced glioma cells). The
      differentially expressed genes (DEGs) were screened using limma package and then
      annotated. Afterwards, the Database for Annotation, Visualization, and Integrated
      Discovery (DAVID) software was applied to perform enrichment analysis for the
      DEGs. Furthermore, the protein-protein interaction (PPI) network and
      transcriptional regulatory network were constructed using Cytoscape software.
      RESULTS: Total 529 DEGs were identified in the normal glioma cells compared with
      the CEBPB-silenced glioma cells, including 336 up-regulated and 193 down
      regulated genes. The significantly enriched pathways included chemokine signaling
      pathway (which involved CCL2), focal adhesion (which involved THBS1 and THBS2),
      TGF-beta signaling pathway (which involved THBS1, THBS2, SMAD5, and SMAD6) and
      chronic myeloid leukemia (which involved TGFBR2 and CCND1). In the PPI network,
      CCND1 (degree = 29) and CCL2 (degree = 12) were hub nodes. Additionally, CEBPB
      and TCF12 might function in glioma through targeting others (CEBPB -> TCF12,
      CEBPB -> TGFBR2, and TCF12 -> TGFBR2). CONCLUSIONS: CEBPB might act in glioma by
      regulating CCL2, CCND1, THBS1, THBS2, SMAD5, SMAD6, TGFBR2, and TCF12.

PMID- 27716260
TI  - Perinatal mortality associated with use of uterotonics outside of Comprehensive
      Emergency Obstetric and Neonatal Care: a cross-sectional study.
AB  - BACKGROUND: Prior studies have shown that using uterotonics to augment or induce
      labor before arrival at comprehensive Emergency Obstetric and Neonatal Care
      (CEmONC) settings (henceforth, "outside uterotonics") may contribute to perinatal
      mortality in low- and middle-income countries. We estimate its effect on
      perinatal mortality in rural Bangladesh. METHODS: Using hospital records (23986
      singleton term births, Jan 1, 2009-Dec 31, 2015) from rural Bangladesh, we use a
      logistic regression model to estimate the increased risk of perinatal death from
      uterotonics administered outside a CEmONC facility. RESULTS: Among term births
      (>=37 weeks gestation), the risk of perinatal death adjusted for key confounders
      is significantly increased among women reporting uterotonic use outside of CEmONC
      (OR = 3 . 0, 95 % CI = 2 . 4,3 . 7). This increased risk is particularly high for
      fresh stillbirths (OR = 4 . 0, 95 % CI = 3 . 0,5 . 3) and intrapartum-related
      causes of early neonatal deaths (birth asphyxia) (OR = 3 . 1, 95 % CI = 2 . 2,4 .
      5). CONCLUSIONS: In this sample, outside uterotonic use was associated with
      substantially increased risk of fresh stillbirths, deaths due to birth asphyxia,
      and all perinatal deaths. In settings of high uterotonic use outside of
      controlled settings, substantial improvement in both stillbirth and early
      neonatal mortality may be made by reducing such use.

PMID- 27716261
TI  - Enhancing health care equity with Indigenous populations: evidence-based
      strategies from an ethnographic study.
AB  - BACKGROUND: Structural violence shapes the health of Indigenous peoples globally,
      and is deeply embedded in history, individual and institutional racism, and
      inequitable social policies and practices. Many Indigenous communities have
      flourished, however, the impact of colonialism continues to have profound health
      effects for Indigenous peoples in Canada and internationally. Despite increasing
      evidence of health status inequities affecting Indigenous populations, health
      services often fail to address health and social inequities as routine aspects of
      health care delivery. In this paper, we discuss an evidence-based framework and
      specific strategies for promoting health care equity for Indigenous populations.
      METHODS: Using an ethnographic design and mixed methods, this study was conducted
      at two Urban Aboriginal Health Centres located in two inner cities in Canada,
      which serve a combined patient population of 5,500. Data collection included in
      depth interviews with a total of 114 patients and staff (n = 73 patients; n = 41
      staff), and over 900 h of participant observation focused on staff members'
      interactions and patterns of relating with patients. RESULTS: Four key dimensions
      of equity-oriented health services are foundational to supporting the health and
      well-being of Indigenous peoples: inequity-responsive care, culturally safe care,
      trauma- and violence-informed care, and contextually tailored care. Partnerships
      with Indigenous leaders, agencies, and communities are required to operationalize
      and tailor these key dimensions to local contexts. We discuss 10 strategies that
      intersect to optimize effectiveness of health care services for Indigenous
      peoples, and provide examples of how they can be implemented in a variety of
      health care settings. CONCLUSIONS: While the key dimensions of equity-oriented
      care and 10 strategies may be most optimally operationalized in the context of
      interdisciplinary teamwork, they also serve as health equity guidelines for
      organizations and providers working in various settings, including individual
      primary care practices. These strategies provide a basis for organizational-level
      interventions to promote the provision of more equitable, responsive, and
      respectful PHC services for Indigenous populations. Given the similarities in
      colonizing processes and Indigenous peoples' experiences of such processes in
      many countries, these strategies have international applicability.

PMID- 27716263
TI  - Serum bicarbonate concentration and the risk of cardiovascular disease and death
      in type 2 diabetes: the Fremantle Diabetes Study.
AB  - BACKGROUND: Serum bicarbonate is associated with mortality, heart failure (HF)
      and progression of renal failure in studies of healthy people and patients with
      chronic kidney disease, but the significance of these observations in unselected
      patients with diabetes in the general population is unknown. The aim of this
      study was to determine whether serum bicarbonate was associated with mortality
      and cardiovascular disease risk in type 2 diabetes. METHODS: Baseline serum
      bicarbonate was available for 1283 well-characterized community-based patients
      (mean +/- SD age 64.1 +/- 11.3 years, 48.7 % males) from the longitudinal
      observational Fremantle Diabetes Study followed for a mean of 12 years.
      Associations between serum bicarbonate and mortality, coronary heart disease
      (CHD) and incident HF were analysed using Cox proportional hazards regression.
      RESULTS: Serum bicarbonate was independently and negatively associated with
      incident CHD. For each 1 mmol/L increase in bicarbonate, the hazard ratio for CHD
      was 0.95 (95 % confidence interval 0.92-0.99) after adjustment for age as time
      scale, age at baseline, sex, English fluency, diabetes duration, loge(serum
      triglycerides), loge(urinary albumin: creatinine ratio), peripheral sensory
      neuropathy and peripheral arterial disease. There were no independent
      associations between serum bicarbonate and all-cause mortality [0.98 (0.95
      1.004)] or incident HF [0.99 (0.95-1.03)]. CONCLUSIONS: Serum bicarbonate was a
      significant independent predictor of incident CHD but not death or HF in
      community-based patients with type 2 diabetes. This supports intervention trials
      of bicarbonate replacement in type 2 patients at risk of CHD and who have a low
      serum bicarbonate concentration.

PMID- 27716264
TI  - Current state of ethics literature synthesis: a systematic review of reviews.
AB  - BACKGROUND: Modern standards for evidence-based decision making in clinical care
      and public health still rely solely on eminence-based input when it comes to
      normative ethical considerations. Manuals for clinical guideline development or
      health technology assessment (HTA) do not explain how to search, analyze, and
      synthesize relevant normative information in a systematic and transparent manner.
      In the scientific literature, however, systematic or semi-systematic reviews of
      ethics literature already exist, and scholarly debate on their opportunities and
      limitations has recently bloomed. METHODS: A systematic review was performed of
      all existing systematic or semi-systematic reviews for normative ethics
      literature on medical topics. The study further assessed how these reviews report
      on their methods for search, selection, analysis, and synthesis of ethics
      literature. RESULTS: We identified 84 reviews published between 1997 and 2015 in
      65 different journals and demonstrated an increasing publication rate for this
      type of review. While most reviews reported on different aspects of search and
      selection methods, reporting was much less explicit for aspects of analysis and
      synthesis methods: 31 % did not fulfill any criteria related to the reporting of
      analysis methods; for example, only 25 % of the reviews reported the ethical
      approach needed to analyze and synthesize normative information. CONCLUSIONS:
      While reviews of ethics literature are increasingly published, their reporting
      quality for analysis and synthesis of normative information should be improved.
      Guiding questions are: What was the applied ethical approach and technical
      procedure for identifying and extracting the relevant normative information
      units? What method and procedure was employed for synthesizing normative
      information? Experts and stakeholders from bioethics, HTA, guideline development,
      health care professionals, and patient organizations should work together to
      further develop this area of evidence-based health care.

PMID- 27716262
TI  - New aspects in the management of pneumonia.
AB  - Despite improvements in the management of community-acquired pneumonia (CAP),
      morbidity and mortality are still high, especially in patients with more severe
      disease. Early and appropriate antibiotics remain the cornerstone in the
      treatment of CAP. However, two aspects seem to contribute to a worse outcome: an
      uncontrolled inflammatory reaction and an inadequate immune response. Adjuvant
      treatments, such as corticosteroids and intravenous immunoglobulins, have been
      proposed to counterbalance these effects. The use of corticosteroids in patients
      with severe CAP and a strong inflammatory reaction can reduce the time to
      clinical stability, the risk of treatment failure, and the risk of progression to
      acute respiratory distress syndrome. The administration of intravenous
      immunoglobulins seems to reinforce the immune response to the infection in
      particular in patients with inadequate levels of antibodies and when an enriched
      IgM preparation has been used; however, more studies are needed to determinate
      their impact on outcome and to define the population that will receive more
      benefit.

PMID- 27716265
TI  - Erratum to: Validity of data collected in BIOREG, the Austrian register for
      biological treatment in rheumatology: current practice of bDMARD therapy in
      rheumatoid arthritis in Austria.

PMID- 27716266
TI  - Drug prescribing patterns at primary health care level and related out-of-pocket
      expenditures in Tajikistan.
AB  - BACKGROUND: The Government of Tajikistan is reforming its health system to make
      access more equitable. Nonetheless, out-of-pocket expenditures (OPE) remain a key
      modality for purchasing health care. Drugs remain a major driver of household
      expenditures for health. We conducted a household survey to investigate drug
      prescribing patterns at primary health care (PHC) level as well as the related
      OPE. METHODS: Adult patients in eight districts who had visited a PHC facility in
      the period March to May 2014 were interviewed at home, using a structured
      questionnaire. A descriptive analysis was conducted and regression models were
      constructed to identify factors influencing the number of drugs provided and the
      types of drugs prescribed. RESULTS: There were 1281 (80.1 %) patients who
      received a drug prescription after visiting a doctor at PHC level. 16.2 % of them
      had five or more drugs prescribed concomitantly. The number of drugs prescribed
      to patients ranged from 0 to 8 and was statistically different across regions
      (RRS region =3.3; Khatlon region = 3.1; p = 0.05), after adjusting for age and
      sex. In 31.1 % of cases, prescriptions included an intra-venous (IV) injection;
      in 45.6 % of cases, a non-IV injection; in 52.9 % of cases, an antibiotic; and in
      61.0 % of cases, vitamins. Patients suffering from a respiratory disease had
      higher odds of being prescribed an IV injection and antibiotics. Vitamins were
      widely prescribed across all diseases. In 94.5 % of cases, the patients
      interviewed procured at least one of the prescribed drugs. Among those who
      received a prescription, 2.0 % were not able to procure at least one drug due to
      a lack of money. In 94.9 % of cases, respondents reported purchasing drugs in
      private pharmacies. Median expenditures for drugs procured following consultation
      were 45 TS (US$ 6.9) corresponding to 77.6 % of total expenditures related to the
      visit (58 TS, US$ 8.8). CONCLUSIONS: In a context where OPE are important, drugs
      represent an important income source for health service providers. Such a
      situation does not favour rational prescribing nor efficient service delivery,
      and is potentially harmful for patients. In particular, the economic
      ramifications cause high levels of expenditure for patients and households with
      detrimental, knock-on effects in the more vulnerable segments of the population.

PMID- 27716268
TI  - Perceived effective and feasible strategies to promote healthy eating in young
      children: focus groups with parents, family child care providers and daycare
      assistants.
AB  - BACKGROUND: The aim of the current study is to identify strategies to promote
      healthy eating in young children that can be applied by caregivers, based on
      their own perceptions of effectiveness and feasibility. Whereas previous research
      mainly focused on parental influences on children's eating behavior, the growing
      role of other caregivers in the upbringing of children can no longer be denied.
      METHODS: Four focus groups were conducted with three types of caregivers of post
      weaning children under 6 years old: parents (n = 14), family child care providers
      (n = 9), and daycare assistants (n = 10). The audiotaped focus group discussions
      were transcribed and imported into Nvivo 10.0 for thematic analysis. The
      behaviors put forward by the caregivers were categorized within three broad
      dimensions: global influences, general behaviors, and specific feeding practices.
      RESULTS: Perceived effective strategies to promote healthy eating behavior in
      children included rewards, verbal encouragement, a taste-rule, sensory
      sensations, involvement, variation, modeling, repeated exposure, and a peaceful
      atmosphere. Participants mainly disagreed on the perceived feasibility of each
      strategy, which largely depended on the characteristics of the caregiving setting
      (e.g. infrastructure, policy). CONCLUSIONS: Based on former research and the
      current results, an intervention to promote healthy eating behaviors in young
      children should be adapted to the caregiving setting or focus on specific feeding
      practices, since these involve simple behaviors that are not hindered by the
      limitations of the caregiving setting. Due to various misconceptions regarding
      health-promoting strategies, clear instructions about when and how to use these
      strategies are necessary.

PMID- 27716269
TI  - User involvement and experiential knowledge in interprofessional rehabilitation:
      a grounded theory study.
AB  - BACKGROUND: User involvement is increasingly important in developing relevant
      health care services. The aim of this study was to contribute to a deeper
      understanding of user involvement and patients' experiential knowledge as
      recognized and incorporated into clinical practice by rehabilitation
      professionals. METHODS: A qualitative design using a grounded theory approach was
      applied. Data were collected by observations of the interprofessional meetings at
      two rehabilitation units treating patients with traumatic brain injury and
      multiple trauma and by individual semi-structured interviews with rehabilitation
      professionals. RESULTS: The professionals recognized and incorporated user
      involvement into clinical practice as formal or authentic. Formal user
      involvement was sometimes considered pro forma. Incorporating patient'
      experiential knowledge was considered a part of authentic user involvement.
      Possible gaps between the patients' experiential knowledge and professional
      expertise were recognized. Challenges included dealing with 'artifacts', sources
      of information external to the patients' own experiences, and addressing the
      patients' possibly reduced insight due to trauma. CONCLUSION: Patients'
      experiential knowledge was recognized as an essential component of the
      professionals' knowledge base. The professionals considered user involvement and
      patients' experiential knowledge as part of their clinical practice.
      Implementation of user involvement and contribution of patients' experiential
      knowledge could be improved by understanding the issues raised in practice, such
      as possible negative consequences of user involvement in form of burdening or
      disempowering the patients. A better understanding of the characteristics and
      measures of user involvement is necessary in order to be able to offer its full
      benefits for both the patients and the professionals.

PMID- 27716267
TI  - Economic evaluation of treatments for patients with localized prostate cancer in
      Europe: a systematic review.
AB  - BACKGROUND: Our objective was to assess the efficiency of treatments in patients
      with localized prostate cancer, by synthesizing available evidence from European
      economic evaluations through systematic review. METHODS: Articles published 2000
      2015 were searched in MEDLINE, EMBASE and NHS EED (Prospero protocol
      CRD42015022063). Two authors independently selected studies for inclusion and
      extracted the data. A third reviewer resolved discrepancies. We included European
      economic evaluations or cost comparison studies, of any modality of surgery or
      radiotherapy treatments, regardless the comparator/s. Drummond's Checklist was
      used for quality assessment. RESULTS: After reviewing 8,789 titles, 13 European
      eligible studies were included: eight cost-utility, two cost-effectiveness, one
      cost-minimization, and two cost-comparison analyses. Of them, five compared
      interventions with expectant management, four contrasted robotic with non robotic
      assisted surgery, three assessed new modalities of radiotherapy, and three
      compared radical prostatectomy with brachytherapy. All but two studies scored >=8
      in the quality checklist. Considering scenario and comparator, three
      interventions were qualified as dominant strategies (active surveillance, robotic
      assisted surgery and IMRT), and six were cost-effective (radical prostatectomy,
      robotic-assisted surgery, IMRT, proton therapy, brachytherapy, and 3DCRT).
      However, QALY gains in most of them were small. For interventions considered as
      dominant strategies, QALY gain was 0.013 for active surveillance over radical
      prostatectomy; and 0.007 for robotic-assisted over non-robotic techniques. The
      highest QALY gains were 0.57-0.86 for radical prostatectomy vs watchful waiting,
      and 0.72 for brachytherapy vs conventional radiotherapy. CONCLUSIONS: Currently,
      relevant treatment alternatives for localized prostate cancer are scarcely
      evaluated in Europe. Very limited available evidence supports the cost
      effectiveness of radical prostatectomy over watchful waiting, brachytherapy over
      radical prostatectomy, and new treatment modalities over traditional procedures.
      Relevant disparities were detected among studies, mainly based on effectiveness.
      These apparently contradictory results may be reflecting the difficulty of
      interpreting small differences between treatments regarding QALY gains.

PMID- 27716271
TI  - Possibly preventable cardiac arrest in a morbidly obese patient - a comment on
      the 2015 ERC guidelines.
AB  - BACKGROUND: The incidence of overweight and obesity has been steadily on the rise
      and has reached epidemic proportions in various countries and this represents a
      well-known major health problem. Nevertheless, current guidelines for
      resuscitation do not include special sequences of action in this subset of
      patients. The aim of this letter is to bring this controversy into focus and to
      suggest alterations of the known standard cardiopulmonary resuscitation in the
      obese. CASE PRESENTATION: An obese patient weighing 272 kg fell to the floor,
      afterwards being unable to get up again. Thus, emergency services were called for
      assistance. There were no signs or symptoms signifying that the person had been
      harmed in consequence of the fall. Only when brought into a supine position the
      patient suffered an immediate cardiac arrest. Cardiopulmonary resuscitation was
      performed but there was no return of a stable spontaneous circulation until the
      patient was brought into a full lateral position. In spite of immediate emergency
      care the patient ultimately suffered a lethal hypoxic brain damage. CONCLUSION: A
      full lateral position should be considered in obese patients having a cardiac
      arrest as it might help to re-establish stable circulatory conditions.

PMID- 27716270
TI  - The antidepressant-like effects of pioglitazone in a chronic mild stress mouse
      model are associated with PPARgamma-mediated alteration of microglial activation
      phenotypes.
AB  - BACKGROUND: Discoveries that microglia-mediated neuroinflammation is involved in
      the pathological process of depression provided a new strategy for novel
      antidepressant therapy. Peroxisome proliferator-activated receptor gamma
      (PPARgamma) is a nuclear receptor regulating inflammation and microglial
      polarization and, therefore, a potential target for resolving depressive
      disorders. Our hypothesis was that antidepressant effects could be achieved
      through anti-inflammatory and neuroprotective activities by PPARgamma-dependent
      microglia-modulating agents. METHODS: Chronic mild stress (CMS) treatment was
      performed on C57BL/6 mice for 6 weeks. After 3 weeks with the CMS procedure,
      depressive-like behaviors were evaluated by sucrose preference (SP), tail
      suspension test (TST), forced swimming test (FST), and locomotor activity.
      Pioglitazone was administered intragastrically once per day for 3 weeks at
      different doses. Neuroinflammatory cytokines were determined by real time-PCR (RT
      PCR), enzyme-linked immunosorbent assay (ELISA), and western blot. The activated
      microglial state was confirmed by immunohistochemistry. N9 microglial cells were
      subjected to lipopolysaccharide, pioglitazone, and GW9662 to discuss the
      phenotype of activated microglia by RT-PCR, ELISA, and western blot. RESULTS: It
      was demonstrated that the PPARgamma agonist pioglitazone (2.5 mg/kg) ameliorated
      depression-like behaviors in CMS-treated mice, as indicated by body weight (BW),
      the SP test, the FST, and the TST. The amelioration of the depression was blocked
      by the PPARgamma antagonist GW9662. The expression of M1 markers (IL-1beta, IL-6,
      TNFalpha, iNOS, and CCL2) increased, and the gene expression of M2 markers (Ym1,
      Arg1, IL-4, IL-10, and TGFbeta) decreased in the hippocampus of the stress
      treated mice. Pioglitazone significantly inhibited the increased numbers and
      morphological alterations of microglia in the hippocampus, reduced the elevated
      expression of microglial M1 markers, and increased the downgraded expression of
      microglial M2 markers in C57BL/6 mice exposed to CMS. In an in vitro experiment,
      pioglitazone reversed the imbalance of M1 and M2 inflammatory cytokines, which is
      correlated with the inhibition of nuclear factor kB activation and is expressed
      in LPS-stimulated N9 microglial cells. CONCLUSIONS: We showed that pioglitazone
      administration induce the neuroprotective phenotype of microglia and ameliorate
      depression-like behaviors in CMS-treated C57BL/6 mice. These data suggested that
      the microglia-modulating agent pioglitazone present a beneficial choice for
      depression.

PMID- 27716272
TI  - The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by
      inducing apoptosis and cell cycle arrest via p21-dependent pathways.
AB  - BACKGROUND: The formation of new lymphatic vessels provides an additional route
      for tumour cells to metastasize. Therefore, inhibiting lymphangiogenesis
      represents an interesting target in cancer therapy. First evidence suggests that
      histone deacetylase inhibitors (HDACi) may mediate part of their antitumor
      effects by interfering with lymphangiogenesis. However, the underlying mechanisms
      of HDACi induced anti-lymphangiogenic properties are not fully investigated so
      far and in part remain unknown. METHODS: Human lymphatic endothelial cells (LEC)
      were cultured in vitro and treated with or without HDACi. Effects of HDACi on
      proliferation and cell cycle progress were analysed by BrdU assay and flow
      cytometry. Apoptosis was measured by quantifying mono- and oligonucleosomes in
      the cytoplasmic fraction of cell lysates. In vitro lymphangiogenesis was
      investigated using the Matrigel short term lymphangiogenesis assay. The effects
      of TSA on cell cycle regulatory proteins and apoptosis-related proteins were
      examined by western blotting, immunofluorescence staining and semi-quantitative
      RT-PCR. Protein- and mRNA half-life of p21 were analysed by western blotting and
      quantitative RT-PCR. The activity of the p21 promoter was determined using a dual
      luciferase assay and DNA-binding activity of Sp1/3 was investigated using EMSA.
      Furthermore, siRNA assays were performed to analyse the role of p21 and p53 on
      TSA-mediated anti-lymphangiogenic effects. RESULTS: We found that HDACi inhibited
      cell proliferation and that the pan-HDACi TSA induced G0/G1 arrest in LEC. Cell
      cycle arrest was accompanied by up-regulation of p21, p27 and p53. Additionally,
      we observed that p21 protein accumulated in cellular nuclei after treatment with
      TSA. Moreover, we found that p21 mRNA was significantly up-regulated by TSA,
      while the protein and mRNA half-life remained largely unaffected. The promoter
      activity of p21 was enhanced by TSA indicating a transcriptional mechanism.
      Subsequent EMSA analyses showed increased constitutive Sp1/3-dependent DNA
      binding in response to HDACi. We demonstrated that p53 was not required for TSA
      induced p21 expression and growth inhibition of LECs. Interestingly, siRNA
      mediated p21 depletion almost completely reversed the anti-proliferative effects
      of TSA in LEC. In addition, TSA induced apoptosis by cytochrome c release
      contributed to activating caspases-9, -7 and -3 and downregulating the anti
      apoptotic proteins cIAP-1 and -2. CONCLUSIONS: In conclusion, we demonstrate that
      TSA - a pan-HDACi - has distinct anti-lymphangiogenic effects in primary human
      lymphatic endothelial cells by activating intrinsic apoptotic pathway and cell
      cycle arrest via p21-dependent pathways.

PMID- 27716273
TI  - A clinical combined gadobutrol bolus and slow infusion protocol enabling
      angiography, inversion recovery whole heart, and late gadolinium enhancement
      imaging in a single study.
AB  - BACKGROUND: The use of gadolinium contrast agents in cardiovascular magnetic
      resonance is well-established and serves to improve both vascular imaging as well
      as enable late gadolinium enhancement (LGE) imaging for tissue characterization.
      Currently, gadofosveset trisodium, an intravascular contrast agent, combined with
      a three-dimensional inversion recovery balanced steady state free precession (3D
      IR bSSFP) sequence, is commonly used in pediatric cardiac imaging and yields
      excellent vascular imaging, but cannot be used for late gadolinium enhancement.
      Gadofosveset use remains limited in clinical practice, and manufacture was
      recently halted, thus an alternative is needed to allow 3D IR bSSFP and LGE in
      the same study. METHODS: Here we propose a protocol to give a bolus of 0.1 mL/kg
      = 0.1 mmol/kg gadobutrol (GADAVIST/GADOVIST) for time-resolved magnetic resonance
      angiography (MRA). Subsequently, 0.1 mmol/kg is diluted up to 5 or 7.5 mL with
      saline and then loaded into intravenous tubing connected to the patient. A 0.5 mL
      short bolus is infused, then a slow infusion is given at 0.02 or 0.03 mL/s. Image
      navigated (iNAV) 3D IR bSSFP imaging is initiated 45-60 s after the initiation of
      the infusion, with a total image acquisition time of ~5 min. If necessary, LGE
      imaging using phase sensitive inversion recovery reconstruction (PSIR) is
      performed at 10 min after the infusion is initiated. RESULTS: We have
      successfully performed the above protocol with good image quality on 10 patients
      with both time-resolved MRA and 3D IR bSSFP iNAV imaging. Our initial attempts to
      use pencil beam respiratory navigation failed due to signal labeling in the liver
      by the navigator. We have also performed 2D PSIR LGE successfully, with both LGE
      positive and LGE negative results. CONCLUSION: A bolus of gadobutrol, followed
      later by a slow infusion, allows time-resolved MRA, 3D IR bSSFP using the iNAV
      navigation technique, and LGE imaging, all in a single study with a single
      contrast agent.

PMID- 27716274
TI  - Current perspectives on cardiovascular outcome trials in diabetes.
AB  - Cardiovascular disease (CVD) is one of the most common diabetes-associated
      complications, as well as a leading cause for death in type 2 diabetes patients
      (T2D). Despite the well-known correlation between the two, up until the 2008 FDA
      industry guidance for licensing of new anti-hyperglycemic drugs, which required
      an investigation of cardiovascular outcomes (CVO) of glucose-lowering agents,
      only a few studies had looked into the relationship between glucose lowering
      drugs and cardiovascular (CV) risk. Thereafter, CVOT design has focused on non
      inferiority short-term studies on high-risk patient populations aiming at
      capturing CV safety issues. Despite the wealth of information and useful data
      provided by CVOTs, this approach still suffers from certain limitations. The
      present review will condense the main results of the most recently completed
      CVOTs, reflect on the lessons learned, discuss on the issues presented by current
      CVOT design and offer some suggestions for improvement.

PMID- 27716275
TI  - Enhancing implementation science by applying best principles of systems science.
AB  - BACKGROUND: Implementation science holds promise for better ensuring that
      research is translated into evidence-based policy and practice, but interventions
      often fail or even worsen the problems they are intended to solve due to a lack
      of understanding of real world structures and dynamic complexity. While systems
      science alone cannot possibly solve the major challenges in public health,
      systems-based approaches may contribute to changing the language and methods for
      conceptualising and acting within complex systems. The overarching goal of this
      paper is to improve the modelling used in dissemination and implementation
      research by applying best principles of systems science. DISCUSSION: Best
      principles, as distinct from the more customary term 'best practices', are used
      to underscore the need to extract the core issues from the context in which they
      are embedded in order to better ensure that they are transferable across
      settings. Toward meaningfully grappling with the complex and challenging problems
      faced in adopting and integrating evidence-based health interventions and
      changing practice patterns within specific settings, we propose and illustrate
      four best principles derived from our systems science experience: (1) model the
      problem, not the system; (2) pay attention to what is important, not just what is
      quantifiable; (3) leverage the utility of models as boundary objects; and (4)
      adopt a portfolio approach to model building. To improve our mental models of the
      real world, system scientists have created methodologies such as system dynamics,
      agent-based modelling, geographic information science and social network
      simulation. To understand dynamic complexity, we need the ability to simulate.
      Otherwise, our understanding will be limited. The practice of dynamic systems
      modelling, as discussed herein, is the art and science of linking system
      structure to behaviour for the purpose of changing structure to improve
      behaviour. A useful computer model creates a knowledge repository and a virtual
      library for internally consistent exploration of alternative assumptions.
      CONCLUSION: Among the benefits of systems modelling are iterative practice,
      participatory potential and possibility thinking. We trust that the best
      principles proposed here will resonate with implementation scientists; applying
      them to the modelling process may abet the translation of research into effective
      policy and practice.

PMID- 27716276
TI  - Elevations in growth hormone and glucagon-like peptide-2 levels on admission are
      associated with increased mortality in trauma patients.
AB  - BACKGROUND: Burn and trauma patients present a clinical challenge due to
      metabolic derangements and hypermetabolism that result in a prolonged catabolic
      state with impaired healing and secondary complications, including ventilator
      dependence. Previous work has shown that circulating levels of growth hormone
      (GH) are predictive of mortality in critically ill adults, but few studies have
      examined the prognostic potential of GH levels in adult trauma patients. METHODS:
      To investigate the utility of GH and other endocrine responses in the prediction
      of outcomes, we conducted a prospective, observational study of adult burn and
      trauma patients. We evaluated the serum concentration of GH, insulin-like growth
      factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), and glucagon-like peptide-2
      (GLP-2) weekly for up to 6 weeks in 36 adult burn and trauma patients admitted
      between 2010 and 2013. RESULTS: Non-survivors had significantly higher levels of
      GH and GLP-2 on admission than survivors. DISCUSSION: This study demonstrates
      that GH has potential as a predictor of mortality in critically ill trauma and
      burn patients. Future studies will focus on not only the role of GH, but also GLP
      2, which was shown to correlate with mortality in this study with a goal of
      offering early, targeted therapeutic interventions aimed at decreasing mortality
      in the critically injured. CONCLUSIONS: GH and GLP-2 may have clinical utility
      for outcome prediction in adult trauma patients.

PMID- 27716277
TI  - Array-CGH diagnosis in ovarian failure: identification of new molecular actors
      for ovarian physiology.
AB  - BACKGROUND: Ovarian failure (OF) is considered premature if it occurs before the
      age of 40. This study investigates the genetic aetiology underlying OF in women
      under the age of 40 years. METHODS: We conducted an experimental prospective
      study performing all genome microarrays in 60 patients younger than 40 years
      presenting an OF revealed by a decrease of circulating Anti-Mullerian Hormone
      (AMH) and leading to an oocyte donation program. RESULTS: We identified nine
      significant copy number variations (CNVs) including candidate genes potentially
      implicated in reproductive function. These genes are principally involved in cell
      division and chromosome segregation (SYCE1, CLASP1, CENP-A, CDC16), in ciliary
      development and/or function (RSPH1, KIF24), are linked with known gonadal genes
      or expressed in female genital tract (CSMD1, SEMA6D, KIAA1324). CONCLUSIONS: Our
      data strengthen the idea that microarrays should be used in combination with
      karyotype for aetiological assessment of patients with OF. This analysis may have
      a therapeutic impact as the identification of new molecular actors for gonadal
      development or ovarian physiology is useful for the prediction of an ovarian
      reserve decline and makes possible preventive fertility preservation.

PMID- 27716278
TI  - A systematic review on the rotational thrombelastometry (ROTEM(r)) values for the
      diagnosis of coagulopathy, prediction and guidance of blood transfusion and
      prediction of mortality in trauma patients.
AB  - INTRODUCTION: Viscoelastic assays have been promoted as an improvement over
      traditional coagulation tests in the management of trauma patients. Rotational
      thromboelastometry (ROTEM(r)) has been used to diagnose coagulopathy and guide
      hemostatic therapy in trauma. This systematic review of clinical studies in
      trauma investigates the ROTEM(r) parameters thresholds used for the diagnosing
      coagulopathy, predicting and guiding transfusion and predicting mortality.
      METHODS: Systematic literature search was performed using MEDLINE, EMBASE and
      Cochrane databases. We included studies without restricting year of publication,
      language or geographic location. Original studies reporting the thresholds of
      ROTEM(r) parameters in the diagnosis or management of coagulopathy in trauma
      patients were included. Data on patient demographics, measures of coagulopathy,
      transfusion and mortality were extracted. We reported our findings according to
      the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)
      guidelines. Quality assessment and risk of bias were performed using Newcastle
      Ottawa Scale (NOS) and the quality assessment of diagnostic accuracy studies
      (QUADAS-2) tools, respectively. RESULTS: A total of 13 observational studies
      involving 2835 adult trauma patients met the inclusion criteria. Nine studies
      were prospective and four were retrospective. There were no randomized controlled
      trials. The quality of the included studies was moderate (mean NOS 5.92, standard
      deviation 0.26). Using QUADAS-2, only 1 study (7.6 %) had low risk of bias in all
      domains, and 9 studies (69.2 %) had low risk of applicability concerns. Outcomes
      from 13 studies were grouped into three categories: diagnosis of coagulopathy (n
      = 10), prediction of massive transfusion or transfusion guidance (n = 6) and
      prediction of mortality (n = 6). Overall, specific ROTEM(r) parameters measured
      (clot amplitude and lysis) in the extrinsically activated test (EXTEM) and the
      fibrin-based extrinsically activated test (FIBTEM) were consistently associated
      with the diagnosis of coagulopathy, increased risk of bleeding and massive
      transfusion, and prediction of mortality. Presence of hyperfibrinolysis by
      ROTEM(r) was associated with increased mortality. CONCLUSIONS: Most of the
      evidence indicates that abnormal EXTEM and FIBTEM clot amplitude (CA5, CA10) or
      maximal clot firmness (MCF) diagnose coagulopathy, and predict blood transfusion
      and mortality. The presence of fibrinolysis (abnormal lysis index [LI30] or
      maximum lysis [ML]) was also associated with mortality. ROTEM(r) thus, may be of
      value in the early management of trauma patients.

PMID- 27716279
TI  - Adapting a weight management tool for Latina women: a usability study of the
      Veteran Health Administration's MOVE!23 tool.
AB  - BACKGROUND: Obesity disproportionately affects Latina women, but few targeted,
      technology-assisted interventions that incorporate tailored health information
      exist for this population. The Veterans Health Administration (VHA) uses an
      online weight management tool (MOVE!23) which is publicly available, but was not
      designed for use in non-VHA populations. METHODS: We conducted a qualitative
      study to determine how interactions between the tool and other contextual
      elements impacted task performance when the target Latina users interacted with
      MOVE!23. We sought to identify and classify specific facilitators and barriers
      that might inform design changes to the tool and its context of use, and in turn
      promote usability. Six English-speaking, adult Latinas were recruited from an
      inner city primary care clinic and a nursing program at a local university in the
      United States to engage in a "Think-Aloud" protocol while using MOVE!23. Sessions
      were recorded, transcribed, and coded to identify interactions between four
      factors that contribute to usability (Tool, Task, User, Context). RESULTS: Five
      themes influencing usability were identified: Technical Ability and Technology
      Preferences; Language Confusion and Ambiguity; Supportive Tool Design and
      Facilitator Guidance; Relevant Examples; and Personal Experience. Features of the
      tool, task, and other contextual factors failed to fully support participants at
      times, impeding task completion. Participants interacted with the tool more
      readily when its language was familiar and content was personally relevant. When
      faced with ambiguity and uncertainty, they relied on the tool's visual cues and
      examples, actively sought relevant personal experiences, and/or requested
      facilitator support. CONCLUSIONS: The ability of our participants to successfully
      use the tool was influenced by the interaction of individual characteristics with
      those of the tool and other contextual factors. We identified both tool-specific
      and context-related changes that could overcome barriers to the use of MOVE!23
      among Latinas. Several general considerations for the design of eHealth tools are
      noted.

PMID- 27716280
TI  - Rab-mediated vesicle trafficking in cancer.
AB  - A large group of small Rab GTPases which mediate secretory and endosomal membrane
      transport, as well as autophagosome biogenesis, are essential components of
      vesicle trafficking machinery. Specific Rab protein together with the cognate
      effectors coordinates the dynamics of trafficking pathway and determines the
      cargo proteins destination. Functional impairments of Rab proteins by mutations
      or post-translational modifications disrupting the regulatory network of vesicle
      trafficking have been implicated in tumorigenesis. Therefore, the vesicle
      transport regulators play essential roles in the mediation of cancer cell
      biology, including uncontrolled cell growth, invasion and metastasis. The context
      dependent role of the same Rab to act as either an oncoprotein or tumor
      suppressor in different cancers is found. Such discrepancies may be due in part
      to the interaction of specific Rab protein with different effectors or cargos in
      various tumors. Here, we review recent advances in the roles of Rab GTPases in
      communicating with other effectors in tumor progression. In this review, we also
      emphasize dysregulation of Rab-mediated membrane delivery shifting normal cell
      behaviors toward malignancy. Thus, recovery of the dysregulated vesicle
      trafficking systems in cancer cells may provide future directions for potential
      strategy to restrain tumor progression.

PMID- 27716281
TI  - Glycine N-methyltransferase deficiency in female mice impairs insulin signaling
      and promotes gluconeogenesis by modulating the PI3K/Akt pathway in the liver.
AB  - BACKGROUND: Glycine N-methyltransferase (GNMT) is abundantly expressed in the
      normal liver but is down-regulated in liver cancer tissues. GNMT knockout (Gnmt-/
      ) mice can spontaneously develop chronic hepatitis, fatty liver, and liver
      cancer. We previously demonstrated that hepatic GNMT is decreased in high-fat
      diet-induced type 2 diabetes mellitus, but its contribution to metabolic syndrome
      is unclear. Here we show that GNMT modulates key aspects of metabolic syndrome in
      mice. METHODS: Eleven-week-old Gnmt-/- and wild-type (WT) mice with a C57BL/6
      genetic background were used in this study. The metabolic defects of GNMT
      deficiency were measured by glucose and insulin tolerance tests, lipid
      homeostasis, gluconeogenesis, and insulin signaling. RESULTS: Gnmt-/- mice,
      especially females, exhibited glucose intolerance and insulin resistance.
      However, their body fat and lean mass, food and water intakes, and energy
      expenditure did not differ from those of WT mice. In addition, glucose-stimulated
      insulin secretion and insulin-stimulated glucagon secretion were normal in the
      serum and pancreatic islets of Gnmt-/- mice. Importantly, we found that GNMT
      deficiency increased lipogenesis and triglycerides in the liver. The elevated
      triglycerides disrupted the ability of insulin to induce Akt and S6 ribosomal
      protein phosphorylation, and then triggered insulin resistance and
      gluconeogenesis in female Gnmt-/- mice. CONCLUSIONS: Our data indicate that
      hepatic GNMT regulates lipid and glucose homeostasis, and provide insight into
      the development of insulin resistance through modulating the PI3K/Akt pathway.

PMID- 27716282
TI  - Spinal cord injury induces astroglial conversion towards neuronal lineage.
AB  - BACKGROUND: Neurons have intrinsic capability to regenerate after lesion, though
      not spontaneously. Spinal cord injury (SCI) causes permanent neurological
      impairments partly due to formation of a glial scar that is composed of
      astrocytes and microglia. Astrocytes play both beneficial and detrimental roles
      on axonal re-growth, however, their precise role after SCI is currently under
      debate. METHODS: We analyzed molecular changes in astrocytes at multiple stages
      after two SCI severities using cell-specific transcriptomic analyses. RESULTS: We
      demonstrate that astrocyte response after injury depends on both time after
      injury and lesion severity. We then establish that injury induces an autologous
      astroglial transdifferentiation where over 10 % of astrocytes express classical
      neuronal progenitor markers including betaIII-tubulin and doublecortin with
      typical immature neuronal morphology. Lineage tracing confirmed that the origin
      of these astrocytes is resident mature, rather than newly formed astrocytes.
      Astrocyte-derived neuronal progenitors subsequently express GABAergic, but not
      glutamatergic-specific markers. Furthermore, we have identified the neural stem
      cell marker fibroblast growth factor receptor 4 (Fgfr4) as a potential autologous
      modulator of astrocytic transdifferentiation following SCI. Finally, we establish
      that astroglial transdifferentiation into neuronal progenitors starts as early as
      72 h and continues to a lower degrees up to 6 weeks post-lesion. CONCLUSION: We
      thus demonstrate for the first time autologous injury-induced astroglial
      conversion towards neuronal lineage that may represent a therapeutic strategy to
      replace neuronal loss and improve functional outcomes after central nervous
      system injury.

PMID- 27716283
TI  - Patient-reported outcomes in transition from high-dose U-100 insulin to human
      regular U-500 insulin in severely insulin-resistant patients with type 2
      diabetes: analysis of a randomized clinical trial.
AB  - BACKGROUND: Initiation and titration of human regular U-500 insulin (U-500R) with
      a dosing algorithm of either thrice daily (TID) or twice daily (BID) improved
      glycemic control with fewer injections in patients with type 2 diabetes treated
      with high-dose, high-volume U-100 insulin. The objective of this analysis was to
      compare patient-reported outcomes between U-500R TID and BID treatment groups in
      this titration-to-target randomized, clinical trial. METHODS: In this 24-week,
      open-label, parallel trial, 325 patients were randomized to TID (n = 162) or BID
      (n = 163) U-500R after a 4-week lead-in period (screening). The Treatment Related
      Impact Measure-Diabetes (TRIM-D) and EQ-5D-5L questionnaires were administered at
      screening, baseline/randomization, and endpoint (24 weeks). The Visual Analog
      Scale-Injection Site Pain (VAS-ISP) was assessed at baseline/randomization, 12
      weeks, and endpoint. RESULTS: The TRIM-D showed statistically significant
      improvements in overall scores from baseline to endpoint for both BID and TID
      groups, most domains in the TID group, and all domains in the BID group. The BID
      group achieved better scores than the TID patients in overall and in treatment
      burden, daily life, and compliance domains (p < .05). EQ-5D-5L index scores
      showed no statistically significant differences for TID and BID groups (and no
      differences between TID and BID groups) from baseline to endpoint. VAS-ISP scores
      improved for both treatment groups (-5.60 TID; -6.47 BID; p < .05 for both) from
      baseline to endpoint. CONCLUSIONS: U500 can be successfully titrated for improved
      glycemic control using BID and TID regimens with diabetes-specific Patient
      Reported Outcomes showing improvements in both arms; however, BID had better
      scores than TID in overall, treatment burden, daily life, and compliance domains.
      TRIAL REGISTRATION: These secondary analyses are based on the study first
      received January 22, 2013 and reported in Clinical Trial Registry No.:
      NCT01774968 .

PMID- 27716285
TI  - Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi
      target tyrosine kinase inhibitor, in patients with advanced refractory solid
      tumors.
AB  - BACKGROUND: Anlotinib is a novel multi-target tyrosine kinase inhibitor that is
      designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR alpha/beta, c-Kit, and
      Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of
      anlotinib in patients with advanced refractory solid tumors. METHODS: Anlotinib
      (5-16 mg) was orally administered in patients with solid tumor once a day on two
      schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1).
      Pharmacokinetic sampling was performed in all patients. Twenty-one patients were
      further enrolled in an expanded cohort study on the recommended dose and
      schedule. Preliminary tumor response was also assessed. RESULTS: On the 4/0
      schedule, dose-limiting toxicity (DLT) was grade 3 hypertension at 10 mg. On the
      2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg.
      Pharmacokinetic assessment indicated that anlotinib had long elimination half
      lives and significant accumulation during multiple oral doses. The 2/1 schedule
      was selected, with 12 mg once daily as the maximum tolerated dose for the
      expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small
      cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft
      tissue sarcoma) were assessable for antitumor activity of anlotinib: 3 patients
      had partial response, 14 patients had stable disease including 12 tumor burden
      shrinkage, and 3 had disease progression. The main serious adverse effects were
      hypertension, triglyceride elevation, hand-foot skin reaction, and lipase
      elevation. CONCLUSIONS: At the dose of 12 mg once daily at the 2/1 schedule,
      anlotinib displayed manageable toxicity, long circulation, and broad-spectrum
      antitumor potential, justifying the conduct of further studies.

PMID- 27716284
TI  - Production of lipopeptide biosurfactants by Bacillus atrophaeus 5-2a and their
      potential use in microbial enhanced oil recovery.
AB  - BACKGROUND: Lipopeptides are known as promising microbial surfactants and have
      been successfully used in enhancing oil recovery in extreme environmental
      conditions. A biosurfactant-producing strain, Bacillus atrophaeus 5-2a, was
      recently isolated from an oil-contaminated soil in the Ansai oilfield, Northwest
      China. In this study, we evaluated the crude oil removal efficiency of
      lipopeptide biosurfactants produced by B. atrophaeus 5-2a and their feasibility
      for use in microbial enhanced oil recovery. RESULTS: The production of
      biosurfactants by B. atrophaeus 5-2a was tested in culture media containing eight
      carbon sources and nitrogen sources. The production of a crude biosurfactant was
      0.77 g L-1 and its surface tension was 26.52 +/- 0.057 mN m-1 in a basal medium
      containing brown sugar (carbon source) and urea (nitrogen source). The
      biosurfactants produced by the strain 5-2a demonstrated excellent oil spreading
      activity and created a stable emulsion with paraffin oil. The stability of the
      biosurfactants was assessed under a wide range of environmental conditions,
      including temperature (up to 120  degrees C), pH (2-13), and salinity (0-50 %,
      w/v). The biosurfactants were found to retain surface-active properties under the
      extreme conditions. Additionally, the biosurfactants were successful in a test to
      simulate microbial enhanced oil recovery, removing 90.0 and 93.9 % of crude oil
      adsorbed on sand and filter paper, respectively. Fourier transform infrared
      spectroscopy showed that the biosurfactants were a mixture of lipopeptides, which
      are powerful biosurfactants commonly produced by Bacillus species. CONCLUSIONS:
      The study highlights the usefulness of optimization of carbon and nitrogen
      sources and their effects on the biosurfactants production and further emphasizes
      on the potential of lipopeptide biosurfactants produced by B. atrophaeus 5-2a for
      crude oil removal. The favorable properties of the lipopeptide biosurfactants
      make them good candidates for application in the bioremediation of oil
      contaminated sites and microbial enhanced oil recovery process.

PMID- 27716286
TI  - Use of beta-caryophyllene to combat bacterial dental plaque formation in dogs.
AB  - BACKGROUND: Periodontal disease is a highly prevalent illness that affects many
      dogs, reaching up to 85 % prevalence in individuals over the age of 4 years.
      Currently the drug of choice for combating the formation of dental plaque in
      these animals, the etiologic agent of the disease, is chlorhexidine, which has
      several side effects reported. Thus, surveys are conducted throughout the world
      in order to identify potential substitutes for antimicrobial therapy and
      prevention of periodontal disease. The objective of the work was to evaluate the
      antimicrobial activity of beta-caryophyllene against bacteria from dog's dental
      plaque in vitro and in vivo. The minimum inhibitory concentration was evaluated
      by agar microdilution assay, the induction or inhibition of bacterial adherence
      by sub-inhibitory concentrations in 96-well plates, and reduction of dental
      plaque formation in mongrel dogs subjected to topical solution with beta
      caryophyllene for 15 days. RESULTS: Results showed minimum inhibitory
      concentrations above 100 mg/mL for 25 % of the isolates, 100 mg/mL for 3 %, 50
      mg/mL for 25 %, 25 mg/mL for 12 %, 12.5 mg/mL for 19 % and 6.25 mg/mL for 16 %.
      Bacterial adherences of three Enterococcus sp., one Streptococcus sp., one
      Haemophilus sp., one Aerococcus sp., one Bacillus sp. and one Lactococcus sp.
      isolates were inhibited by subinhibitory concentration. One Lactococcus sp., one
      Bacillus sp. and one Streptococcus sp. were stimulated to adhere by
      concentrations of 0.19, 1.56 and 0.78 mg/mL, respectively. In vivo assay showed
      reduction in dental plaque formation by beta-caryophyllene, with final plaque
      coverage of 23.3 +/- 2.6 % of the total area of the teeth, with significant
      difference compared with chlorhexidine group (37.5 +/- 3.7 % - p < 0.05) and
      negative control group (65.5 +/- 2.5 % - p < 0.001). CONCLUSIONS: The results
      showed that beta-caryophyllene has antimicrobial activity against the
      proliferation of dog's dental plaque-forming bacteria representing a suitable
      alternative to the use of chlorhexidine in prophylaxis and treatment of
      periodontal disease of dogs.

PMID- 27716287
TI  - Modeling neurological diseases with induced pluripotent cells reprogrammed from
      immortalized lymphoblastoid cell lines.
AB  - Patient-specific induced pluripotent stem cells (iPSCs) facilitate understanding
      of the etiology of diseases, discovery of new drugs and development of novel
      therapeutic interventions. A frequently used starting source of cells for
      generating iPSCs has been dermal fibroblasts (DFs) isolated from skin biopsies.
      However, there are also numerous repositories containing lymphoblastoid B-cell
      lines (LCLs) generated from a variety of patients. To date, this rich bioresource
      of LCLs has been underused for generating iPSCs, and its use would greatly expand
      the range of targeted diseases that could be studied by using patient-specific
      iPSCs. However, it remains unclear whether patient's LCL-derived iPSCs (LiPSCs)
      can function as a disease model. Therefore, we generated Parkinson's disease
      patient-specific LiPSCs and evaluated their utility as tools for modeling
      neurological diseases. We established iPSCs from two LCL clones, which were
      derived from a healthy donor and a patient carrying PARK2 mutations, by using
      existing non-integrating episomal protocols. Whole genome sequencing (WGS) and
      comparative genomic hybridization (CGH) analyses showed that the appearance of
      somatic variations in the genomes of the iPSCs did not vary substantially
      according to the original cell types (LCLs, T-cells and fibroblasts).
      Furthermore, LiPSCs could be differentiated into functional neurons by using the
      direct neurosphere conversion method (dNS method), and they showed several
      Parkinson's disease phenotypes that were similar to those of DF-iPSCs. These data
      indicate that the global LCL repositories can be used as a resource for
      generating iPSCs and disease models. Thus, LCLs are the powerful tools for
      generating iPSCs and modeling neurological diseases.

PMID- 27716288
TI  - Methylferulate from Tamarix aucheriana inhibits growth and enhances
      chemosensitivity of human colorectal cancer cells: possible mechanism of action.
AB  - BACKGROUND: Natural products are valuable sources for anticancer agents. In the
      present study, methylferulate (MF) was identified for the first time from Tamarix
      aucheriana. Spectral data were used for identification of MF. The potential of MF
      to control cell growth, cell cycle, apoptosis, generation of reactive oxygen
      species (ROS), cancer cell invasion, nuclear factor kappa B (NFkB) DNA-binding
      activity and proteasomal activities, as well as the enhancement of
      chemosensitivity in human colorectal cancer cells, were evaluated. The possible
      molecular mechanism of MF's therapeutic efficacy was also assessed. METHODS:
      Column chromatography and spectral data were used for isolation and
      identification of MF. MTT, immunofluorescence, flow cytometry, in vitro invasion,
      fluoremetry, EIA and Real time qPCR were used to measure antiproliferative, chemo
      sensitizing effects and other biochemical parameters. RESULTS: MF showed a dose
      dependent anti-proliferative effect on colorectal cancer cells (IC50 = 1.73 - 1.9
      mM) with a nonsignificant cytotoxicity toward normal human fibroblast. Colony
      formation inhibition (P <= 0.001, 0.0001) confirmed the growth inhibition by MF.
      MF arrested cell cycle progression in the S and G2/M phases; induced apoptosis
      and ROS generation; and inhibited NF-kB DNA-binding activity, proteasomal
      activities and cell invasion in colorectal cancer cells. MF up-regulated cyclin
      dependent kinase inhibitors (p19 INK4D, p21WAF1/CIP1, p27KIP1), pro-apoptotic
      gene expression (Bax, Bad, Apaf1, Bid, Bim, Smac) and caspases (caspase 2, 3, 6,
      7, 8, 9). Moreover, MF down-regulated cyclin-dependent kinases (Cdk1, Cdk2) and
      anti-apoptotic gene expression (c-IAP-1, c-IAP-2, Bcl2,FLIP). In addition, MF
      differentially potentiated the sensitivity of colorectal cancer cells to standard
      chemotherapeutic drugs. CONCLUSION: MF showed a multifaceted anti-proliferative
      and chemosensitizing effects. These results suggest the chemotherapeutic and co
      adjuvant potential of MF.

PMID- 27716289
TI  - Vitamin D modifies the associations between circulating betatrophin and
      cardiometabolic risk factors among youths at risk for metabolic syndrome.
AB  - BACKGROUND: Betatrophin has been recently reported to play a role in glucose
      homeostasis by inducing beta-cell proliferation in mice. However, studies in
      human are inconsistent. As a nutritionally-regulated liver-enriched factor, we
      hypothesize that betatrophin might be regulated by vitamin D, and ignorance of
      vitamin D status may explain the discrepancy in previous human studies. The aims
      of this study were to assess the association between circulating betatrophin and
      glucose homeostasis as well as other cardiometabolic variables in a cohort of
      youths at risk for metabolic syndrome and test the possible influence of vitamin
      D status on the association. METHODS: 559 subjects aged 14-28 years were
      recruited from Beijing children and adolescents metabolic syndrome study. All
      underwent a 2 h-oral glucose tolerance test. Serum levels of betatrophin, 25
      hydroxy-vitamin D as well as adipokines including adiponectin and fibroblast
      growth factor 21 (FGF21) were measured by immunoassays. The relationships between
      betatrophin and insulin resistance, beta-cell function, other cardiometabolic
      variables and vitamin D status were evaluated. RESULTS: Participants in the
      highest quartile of betatrophin levels had the highest levels of total
      cholesterol (P < 0.001), triglyceride (P < 0.001) and low-density lipoprotein
      cholesterol (P < 0.001) and the lowest levels of vitamin D (P = 0.003). After
      stratification by vitamin D status, betatrophin in subjects with vitamin D
      deficiency were positively correlated with unfavorable metabolic profiles
      including high blood pressures, dyslipidemia and hyperglycemia, whereas
      betatrophin in those with higher vitamin D levels only showed negative
      association with fasting insulin, 2 h-insulin, and insulin resistance. In
      addition, adiponectin and FGF21 demonstrated the expected associations with
      metabolic parameters. CONCLUSIONS: Elevated betatrophin levels were associated
      with cardiometabolic risk factors in this young population, but the association
      was largely dependent on vitamin D status. These findings may provide valuable
      insights in the regulation of betatrophin and help explain the observed
      discrepancies in literature.

PMID- 27716290
TI  - Neurofeedback training for alcohol dependence versus treatment as usual: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Real-time functional magnetic resonance imaging (rtfMRI) is used for
      neurofeedback training (NFT). Preliminary results suggest that it can help
      patients to control their symptoms. This study uses rtfMRI NFT for relapse
      prevention in alcohol dependence. METHODS/DESIGN: Participants are alcohol
      dependent patients who have completed a detoxification programme within the past
      6 months and have remained abstinent. Potential participants are screened for
      eligibility, and those who are eligible are randomly assigned to the treatment
      group (receiving rtfMRI NFT in addition to treatment as usual) or the control
      group (receiving only treatment as usual). Participants in both groups are
      administered baseline assessments to measure their alcohol consumption and
      severity of dependence and a variety of psychological and behavioural
      characteristics that are hypothesised to predict success with rtfMRI NFT. During
      the following 4 months, experimental participants are given six NFT sessions, and
      before and after each session various alcohol-related measures are taken.
      Participants in the control group are given the same measures to coincide with
      their timing in the experimental group. Eight and 12 months after the baseline
      assessment, both groups are followed up with a battery of measures. The primary
      research questions are whether NFT can be used to teach participants to down
      regulate their brain activation in the presence of alcohol stimuli or to up
      regulate their brain activation in response to pictures related to healthy goal
      pursuits, and, if so, whether this translates into reductions in alcohol
      consumption. The primary outcome measures will be those derived from the
      functional brain imaging data. We are interested in improvements (i.e.,
      reductions) in participants' alcohol consumption from pretreatment levels, as
      indicated by three continuous variables, not simply whether or not the person has
      remained abstinent. The indices of interest are percentage of days abstinent,
      drinks per drinking day, and percentage of days of heavy drinking. General linear
      models will be used to compare the NFT group and the control group on these
      measures. DISCUSSION: Relapse in alcohol dependence is a recurring problem, and
      the present evaluation of the role of rtfMRI in its treatment holds promise for
      identifying a way to prevent relapse. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT02486900 , registered on 26 June 2015.

PMID- 27716291
TI  - Enzymatic fine-tuning for 2-(6-hydroxynaphthyl) beta-D-xylopyranoside synthesis
      catalyzed by the recombinant beta-xylosidase BxTW1 from Talaromyces amestolkiae.
AB  - BACKGROUND: Glycosides are compounds displaying crucial biological roles and
      plenty of applications. Traditionally, these molecules have been chemically
      obtained, but its efficient production is limited by the lack of regio- and
      stereo-selectivity of the chemical synthesis. As an interesting alternative,
      glycosidases are able to catalyze the formation of glycosides in a process
      considered green and highly selective. In this study, we report the expression
      and characterization of a fungal beta-xylosidase in Pichia pastoris. The
      transglycosylation potential of the enzyme was evaluated and its applicability in
      the synthesis of a selective anti-proliferative compound demonstrated. RESULTS:
      The beta-xylosidase BxTW1 from the ascomycete fungus Talaromyces amestolkiae was
      cloned and expressed in Pichia pastoris GS115. The yeast secreted 8 U/mL of beta
      xylosidase that was purified by a single step of cation-exchange chromatography.
      rBxTW1 in its active form is an N-glycosylated dimer of about 200 kDa. The enzyme
      was biochemically characterized displaying a K m and k cat against p-nitrophenyl
      beta-D-xylopyranoside of 0.20 mM and 69.3 s-1 respectively, and its maximal
      activity was achieved at pH 3 and 60  degrees C. The glycan component of rBxTW1
      was also analyzed in order to interpret the observed loss of stability and
      maximum velocity when compared with the native enzyme. A rapid screening of
      aglycone specificity was performed, revealing a remarkable high number of
      potential transxylosylation acceptors for rBxTW1. Based on this analysis, the
      enzyme was successfully tested in the synthesis of 2-(6-hydroxynaphthyl) beta-D
      xylopyranoside, a well-known selective anti-proliferative compound, enzymatically
      obtained for the first time. The application of response surface methodology,
      following a Box-Behnken design, enhanced this production by eightfold, fitting
      the reaction conditions into a multiparametric model. The naphthyl derivative was
      purified and its identity confirmed by NMR. CONCLUSIONS: A beta-xylosidase from
      T. amestolkiae was produced in P. pastoris and purified. The final yields were
      much higher than those attained for the native protein, although some loss of
      stability and maximum velocity was observed. rBxTW1 displayed remarkable acceptor
      versatility in transxylosylation, catalyzing the synthesis of a selective
      antiproliferative compound, 2-(6-hydroxynaphthyl) beta-D-xylopyranoside. These
      results evidence the interest of rBxTW1 for transxylosylation of relevant
      products with biotechnological interest.

PMID- 27716292
TI  - Serological patterns of Actinobacillus pleuropneumoniae, Mycoplasma
      hyopneumoniae, Pasteurella multocida and Streptococcus suis in pig herds affected
      by pleuritis.
AB  - BACKGROUND: Respiratory illness is traditionally regarded as the disease of the
      growing pig, and has historically mainly been associated to bacterial infections
      with focus on Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. These
      bacteria still are of great importance, but continuously increasing herd sizes
      have complicated the scenario and the influence of secondary invaders may have
      been increased. The aim of this study was to evaluate the presence of A.
      pleuropneumoniae and M. hyopneumoniae, as well as that of the secondary invaders
      Pasteurella multocida and Streptococcus suis by serology in four pig herds (A-D)
      using age segregated rearing systems with high incidences of pleuritic lesions at
      slaughter. RESULTS: Pleuritic lesions registered at slaughter ranged from 20.5 to
      33.1 % in the four herds. In herd A, the levels of serum antibodies to A.
      pleuropneumoniae exceeded A450 > 1.5, but not to any other microbe searched for.
      The seroconversion took place early during the fattening period. Similar levels
      of serum antibodies to A. pleuropneumoniae were also recorded in herd B, with a
      subsequent increase in levels of antibodies to P. multocida. Pigs seroconverted
      to both agents during the early phase of the fattening period. In herd C, pigs
      seroconverted to P. multocida during the early phase of the fattening period and
      thereafter to A. pleuropneumoniae. In herd D, the levels of antibodies to P.
      multocida exceeded A450 > 1.0 in absence (A450 < 0.5) of antibodies to A.
      pleuropneumoniae. The levels of serum antibodies to M. hyopneumoniae and to S.
      suis remained below A450 < 1.0 in all four herds. Pigs seroconverted to M.
      hyopneumoniae late during the rearing period (herd B-D), or not at all (herd A).
      CONCLUSION: Different serological patterns were found in the four herds with high
      levels of serum antibodies to A. pleuropneumoniae and P. multocida, either alone
      or in combination with each other. Seroconversion to M. hyopneumoniae late during
      the rearing period or not at all, confirmed the positive effect of age segregated
      rearing in preventing or delaying infections with M. hyopneumoniae. The results
      obtained highlight the necessity of diagnostic investigations to define the true
      disease pattern in herds with a high incidence of pleuritic lesions.

PMID- 27716294
TI  - Erratum to: Simple steps to develop trial follow-up procedures.

PMID- 27716293
TI  - Combined integrated protocol/basket trial design for a first-in-human trial.
AB  - BACKGROUND: Innovative trial designs are sought to streamline drug development in
      rare diseases. Basket- and integrated protocol designs are two of these new
      strategies and have been applied in a handful oncologic trials. We have taken the
      concept outside the realm of oncology and report about a first-in-human
      integrated protocol design that facilitates the transition from phase Ia in
      healthy volunteers to phase Ib in patients with rare complement-mediated
      disorders driven by the classical pathway. RESULTS: We have been conducting a
      prospective, double-blind, randomized, placebo-controlled first-in-human study
      with TNT009, which is a humanized monoclonal antibody directed against the C1s
      subunit of human complement component C1. The trial consisted of three subparts,
      including normal healthy volunteers (part one and two) and a single cohort of
      patients in part three. Patients suffered from various complement-mediated
      diseases sharing the same pathophysiological mechanism, i.e. bullous pemphigoid,
      antibody-mediated rejection of organ transplants, cold agglutinin disease and
      warm autoimmune hemolytic anemia. Primary objective of the trial has been to
      evaluate the safety and tolerability of TNT009 in humans. CONCLUSIONS: This trial
      provides probably the first example that basket trials may not be limited to
      single genetic aberrations, which is overly restrictive, but our trial design
      demonstrates that pathway specificity is a viable paradigm for defining baskets.
      This will hopefully serve as a role model that could benefit other innovative
      drug development programs targeting rare diseases.

PMID- 27716295
TI  - Association of KCTD10, MVK, and MMAB polymorphisms with dyslipidemia and coronary
      heart disease in Han Chinese population.
AB  - BACKGROUND: Several genome-wide association studies have discovered novel loci at
      chromosome 12q24, which includes mevalonate kinase (MVK), methylmalonic aciduria
      (cobalamin deficiency) cbIB type (MMAB), and potassium channel tetramerization
      domain-containing 10 (KCTD10), all of which influence HDL-cholesterol
      concentrations. However, there are few reports on the associations between these
      polymorphisms and HDL-C concentrations in Chinese population. This study aimed to
      evaluate the associations between functional polymorphisms in three genes (MVK,
      MMAB and KCTD10) and HDL-C concentrations, as well as coronary heart disease
      (CHD) susceptibility in Chinese individuals. METHODS: We systematically selected
      and genotyped 18 potentially functional polymorphisms in MVK, MMAB and KCTD10 by
      using the TaqMan OpenArray Genotyping System in a Chinese population including
      399 dyslipidemia cases, 697 CHD cases and 465 controls. Multivariate logistic
      regression analyses were performed to estimate the relationship between the
      genotypes and dyslipidemia, CHD risk with adjustment of relevant confounders.
      RESULTS: Among six polymorphisms showing significant associations with
      dyslipidemia, the minor alleles of rs11066782 in KCTD10, rs11613718 in KCTD10 and
      rs11067233 in MMAB were significantly associated with a decreased risk of CHD
      (additive model: OR = 0.71, 95 % CI = 0.53-0.97, P = 0.029 for rs11066782; OR =
      0.73, 95 % CI = 0.54-0.99, P = 0.044 for rs11613718 and OR = 0.57, 95 % CI = 0.40
      0.80, P = 0.001 for rs11067233). Further combined analysis showed that
      individuals carrying "3-4" favorable alleles presented a 62 % (OR = 0.38, 95 % CI
      = 0.21-0.66) decreased risk of CHD compared with those carrying "0-2" favorable
      alleles. CONCLUSIONS: These findings suggest that rs11066782 in KCTD10,
      rs11613718 in KCTD10 and rs11067233 in MMAB may contribute to the susceptibility
      of CHD by altering plasma HDL-C levels in Han Chinese.

PMID- 27716296
TI  - Health inequalities research in India: a review of trends and themes in the
      literature since the 1990s.
AB  - BACKGROUND: Research on health inequalities can be instrumental in drawing
      attention to the health of socioeconomically vulnerable groups in India in the
      context of rapid economic growth. It can shape the dialogue for public health
      action, emphasizing the need for greater investments in health, and monitor
      effectiveness of health programs. Our objective was to examine trends in studies
      on health inequalities in the last 25 years. METHODS: We conducted a systematic
      literature review of studies on health inequalities published from 1990. The
      year, 1990, marked the beginning of economic reforms and liberalization in India.
      We searched PubMED using key terms to identify 8800 articles between 1990 and
      2016; we identified 1,312 final studies for review. Key domains of analysis
      included measures of equity, health outcomes, populations studied, year of
      publication, study methodology, study focus (descriptive versus analytical), and
      location of main author. RESULTS: We found an increase in studies on health
      inequalities after 2005. About 88 % of the studies utilized quantitative methods
      for analysis. About 8 % of the studies related to health interventions or
      programs; the number of intervention studies have been increasing since 2010. A
      majority of studies were led by authors based in India. Early studies focused on
      mortality, communicable and non-communicable diseases, and nutrition, while later
      studies have focused on non-communicable diseases, mental health, risk factors,
      and injuries. Studies on women and children comprised nearly half of the
      literature; studies on the youth (15-24 years or as defined by the study) and
      elderly have been rising. Wealth and income were the most common measures of
      equity, followed by education and gender. The proportion of studies on wealth,
      education, region and caste have stayed consistent over time, while studies on
      gender disparities have been rising. CONCLUSION: In a country as diverse as India
      with large social inequalities combined with rapid economic growth, research on
      health inequalities has a special significance for policy. We recommend that
      studies on health inequalities in the future focus on evaluations of policy and
      health programs, and on underrepresented health outcomes and populations.

PMID- 27716297
TI  - A randomised controlled trial of three very brief interventions for physical
      activity in primary care.
AB  - BACKGROUND: Very brief interventions (VBIs) for physical activity are promising,
      but there is uncertainty about their potential effectiveness and cost. We
      assessed potential efficacy, feasibility, acceptability, and cost of three VBIs
      in primary care, in order to select the most promising intervention for
      evaluation in a subsequent large-scale RCT. METHODS: Three hundred and ninety
      four adults aged 40-74 years were randomised to a Motivational (n = 83),
      Pedometer (n = 74), or Combined (n = 80) intervention, delivered immediately
      after a preventative health check in primary care, or control (Health Check only;
      n = 157). Potential efficacy was measured as the probability of a positive
      difference between an intervention arm and the control arm in mean physical
      activity, measured by accelerometry at 4 weeks. RESULTS: For the primary outcome
      the estimated effect sizes (95 % CI) relative to the Control arm for the
      Motivational, Pedometer and Combined arms were respectively: +20.3 (-45.0,
      +85.7), +23.5 (-51.3, +98.3), and -3.1 (-69.3, +63.1) counts per minute. There
      was a73% probability of a positive effect on physical activity for each of the
      Motivational and Pedometer VBIs relative to control, but only 46 % for the
      Combined VBI. Only the Pedometer VBI was deliverable within 5 min. All VBIs were
      acceptable and low cost. CONCLUSIONS: Based on the four criteria, the Pedometer
      VBI was selected for evaluation in a large-scale trial. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN02863077 . Retrospectively registered 05/10/2012.

PMID- 27716298
TI  - Collaborative Assessment and Management of Suicidality (CAMS) compared to
      treatment as usual (TAU) for suicidal patients: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Collaborative Assessment and Management of Suicidality (CAMS) is a
      therapeutic framework that appears promising to reduce suicidal ideation and
      suicidal cognition. CAMS has not previously been evaluated in a standard
      specialized mental health care setting for patients with suicidal problems in
      general. In this pragmatic randomized controlled trial (RCT) we will investigate
      if CAMS is more effective than treatment as usual (TAU) in reducing suicidal
      thoughts and behaviors. Effects will also be investigated on mental health and
      symptom relief in general and upon readmissions to inpatient units.
      METHODS/DESIGN: The study is a multicenter, observer-blinded, superiority, two
      armed RCT which will include patients from four clinical departments at Vestre
      Viken Hospital Trust, Norway. We aim to include 100 patients with moderate to
      strong suicidal problems, as defined by a score of 13 or more on Beck's Scale for
      Suicide Ideation - Current. Patients are included regardless of diagnosis.
      Randomization will be performed using a stratified four-block procedure with
      treatment unit as the stratification variable. The duration of treatment will
      vary depending on patients' needs and clinical assessments. Patients are
      interviewed by research staff at four checkpoints: baseline, 2 weeks, 6 months,
      and 12 months. Central outcome measures are the Beck Scale for Suicide Ideation -
      Current, Outcome Questionnaire - 45, and Suicide Attempt Self-Injury Count.
      DISCUSSION: This pragmatic trial is effectuated within the Public Health Care
      System in Norway, where patients have multiple problems and diagnoses and
      therapists have a high work load. Results from this trial are highly
      generalizable to a typical everyday clinical setting, and one should expect
      similar results if CAMS is implemented in the future as a standard component in
      specialized mental health care systems. TRIAL REGISTRATION: Open Science
      Framework: DOI 10.17605/OSF.IO/JHRM2 . Registered 5 July 2015.
      ClinicalTrials.gov: NCT02685943 . Registered on 8 February 2016.

PMID- 27716299
TI  - Perceptions of health managers and professionals about mental health and primary
      care integration in Rio de Janeiro: a mixed methods study.
AB  - BACKGROUND: Community-based primary mental health care is recommended in low and
      middle-income countries. The Brazilian Health System has been restructuring
      primary care by expanding its Family Health Strategy. Due to mental health
      problems, psychosocial vulnerability and accessibility, Matrix Support teams are
      being set up to broaden the professional scope of primary care. This paper aims
      to analyse the perceptions of health professionals and managers about the
      integration of primary care and mental health. METHOD: In this mixed-method study
      18 health managers and 24 professionals were interviewed from different primary
      and mental health care services in Rio de Janeiro. A semi-structured survey was
      conducted with 185 closed questions ranging from 1 to 5 and one open-ended
      question, to evaluate: access, gateway, trust, family focus, primary mental
      health interventions, mental health records, mental health problems, team
      collaboration, integration with community resources and primary mental health
      education. Two comparisons were made: health managers and professionals' (Mann
      Whitney non-parametric test) and health managers' perceptions (Kruskall-Wallis
      non parametric-test) in 4 service designs (General Traditional Outpatients,
      Mental Health Specialised Outpatients, Psychosocial Community Centre and Family
      Health Strategy)(SPSS version 17.0). Qualitative data were subjected to Framework
      Analysis. RESULTS: Firstly, health managers and professionals' perceptions
      converged in all components, except the health record system. Secondly, managers'
      perceptions in traditional services contrasted with managers' perceptions in
      community-based services in components such as mental health interventions and
      team collaboration, and converged in gateway, trust, record system and primary
      mental health education. Qualitative data revealed an acceptance of mental health
      and primary care integration, but a lack of communication between institutions.
      The Mixed Method demonstrated that interviewees consider mental health and
      primary care integration as a requirement of the system, while their perceptions
      and the model of work produced by the institutional culture are inextricably
      linked. CONCLUSION: There is a gap between health managers' and professionals'
      understanding of community-based primary mental health care. The integration of
      different processes of work entails both rethinking workforce actions and
      institutional support to help make changes.

PMID- 27716300
TI  - Seasonal rainfall at long-term migratory staging sites is associated with altered
      carry-over effects in a Palearctic-African migratory bird.
AB  - BACKGROUND: An understanding of year-round habitat use is essential for
      determining how carry-over effects shape population dynamics in long-distance
      migratory songbirds. The recent discovery of long-term migratory staging sites in
      many species, prior to arrival at final wintering sites, adds complexity to
      efforts to decipher non-breeding habitat use and connections between sites. We
      investigated whether habitat conditions during migratory staging carry over to
      influence great reed warbler (Acrocephalus arundinaceus) body condition at final
      wintering sites in Zambia. We asked whether the presence/absence and strength of
      such carry-over effects were modified by contrasting rainfall conditions during 2
      years. RESULTS: First, we found that individuals staging in a dry year had higher
      corticosterone (CORTf) and stable nitrogen isotope values (suggesting higher
      aridity) than birds staging in a wet year, indicating that regional weather
      affected staging conditions. Second, we found that carry-over effects from
      staging habitat conditions (measured via carbon and nitrogen isotopes) to final
      winter site body condition (measured via scaled mass index and beta
      hydroxybutyrate) were only present in a dry year, suggesting that environmental
      factors have consequences for the strength of carry-over effects. Our results
      also suggest that wet conditions at final winter sites may buffer the effects of
      poor staging conditions, at least in the short term, since individuals that
      staged in a dry year had higher scaled mass indices in Zambia than individuals
      that staged in a wet year. CONCLUSIONS: This study provides a first insight into
      the connections between long-term migratory staging sites and final wintering
      sites, and suggests that local environmental factors can modify the strength of
      carry-over effects for long-distance migratory birds.

PMID- 27716302
TI  - Back to the basics of ovarian aging: a population-based study on longitudinal
      anti-Mullerian hormone decline.
AB  - BACKGROUND: Anti-Mullerian hormone (AMH) is currently used as an ovarian reserve
      marker for individualized fertility counseling, but very little is known of
      individual AMH decline in women. This study assessed whether the decline
      trajectory of AMH is uniform for all women, and whether baseline age-specific AMH
      levels remain consistently high or low during this trajectory. METHODS: A total
      of 3326 female participants from the population-based Doetinchem Cohort Study
      were followed with five visits over a 20-year period. Baseline age was 40 +/- 10
      years with a range of 20-59 years. AMH was measured in 12,929 stored plasma
      samples using the picoAMH assay (AnshLabs). Decline trajectories of AMH were
      studied with both chronological age and reproductive age, i.e., time to
      menopause. Multivariable linear mixed effects models characterized the individual
      AMH decline trajectories. RESULTS: The overall rate of AMH decline accelerated
      after 40 years of age. Mixed models with varying age-specific AMH levels and
      decline rates provided the significantly best fit to the data, indicating that
      the fall in AMH levels over time does not follow a fixed pattern for individual
      women. AMH levels remained consistent along individual trajectories of age, with
      an intraclass correlation coefficient (ICC) of 0.87. The ICC of 0.32 for AMH
      trajectories with time to menopause expressed the large variation in AMH levels
      at a given time before the menopause. The differences between low and high age
      specific AMH levels remained distinguishable, but became increasingly smaller
      with increasing chronological and reproductive age. CONCLUSIONS: This is the
      first study to characterize individual AMH decline over a long time period and
      broad age range. The varying AMH decline rates do not support the premise of a
      uniform AMH decline trajectory. Although age-specific AMH levels remain
      consistently high or low with increasing age, the converging trajectories and
      variance of AMH levels at a given time before menopause shed doubt on the added
      value of AMH to represent individualized reproductive age.

PMID- 27716303
TI  - Realist trials and the testing of context-mechanism-outcome configurations: a
      response to Van Belle et al.
AB  - BACKGROUND: Van Belle et al. argue that our attempt to pursue realist evaluation
      via a randomised trial will be fruitless because we misunderstand realist
      ontology (confusing intervention mechanisms with intervention activities and with
      statistical mediation analyses) and because RCTs cannot comprehensively examine
      how and why outcome patterns are caused by mechanisms triggered in specific
      contexts. METHODS: Through further consideration of our trial methods, we explain
      more fully how we believe complex social interventions work and what realist
      evaluation should aim to do within a trial. RESULTS: Like other realists, those
      undertaking realist trials assume that: social interventions provide resources
      which local actors may draw on in actions that can trigger mechanisms; these
      mechanisms may interact with contextual factors to generate outcomes; and data in
      the 'empirical' realm can be used to test hypotheses about mechanisms in the
      'real' realm. Whether or not there is sufficient contextual diversity to test
      such hypotheses is a contingent not a necessary feature of trials. Previous
      exemplars of realist evaluation have compared empirical data from intervention
      and control groups to test hypotheses about real mechanisms. There is no
      inevitable reason why randomised trials should not also be able to do so. Random
      allocation merely ensures the comparability of such groups without necessarily
      causing evaluation to lapse from a realist into a 'positivist' or 'post
      positivist' paradigm. CONCLUSIONS: Realist trials are ontologically and
      epistemologically plausible. Further work is required to assess whether they are
      feasible and useful but such work should not be halted on spurious philosophical
      grounds.

PMID- 27716301
TI  - Subsidized health insurance coverage of people in the informal sector and
      vulnerable population groups: trends in institutional design in Asia.
AB  - BACKGROUND: Many low- and middle-income countries with a social health insurance
      system face challenges on their road towards universal health coverage (UHC),
      especially for people in the informal sector and vulnerable population groups or
      the informally employed. One way to address this is to subsidize their
      contributions through general government revenue transfers to the health
      insurance fund. This paper provides an overview of such health financing
      arrangements in Asian low- and middle-income countries. The purpose is to assess
      the institutional design features of government subsidized health insurance type
      arrangements for vulnerable and informally employed population groups and to
      explore how these features contribute to UHC progress. METHODS: This regional
      study is based on a literature search to collect country information on the
      specific institutional design features of such subsidization arrangements and
      data related to UHC progress indicators, i.e. population coverage, financial
      protection and access to care. The institutional design analysis focuses on
      eligibility rules, targeting and enrolment procedures; financing arrangements;
      the pooling architecture; and benefit entitlements. RESULTS: Such financing
      arrangements currently exist in 8 countries with a total of 14 subsidization
      schemes. The most frequent groups covered are the poor, older persons and
      children. Membership in these arrangements is mostly mandatory as is full
      subsidization. An integrated pool for both the subsidized and the contributors
      exists in half of the countries, which is one of the most decisive features for
      equitable access and financial protection. Nonetheless, in most schemes,
      utilization rates of the subsidized are higher compared to the uninsured, but
      still lower compared to insured formal sector employees. Total population
      coverage rates, as well as a higher share of the subsidized in the total insured
      population are related with broader eligibility criteria. CONCLUSIONS: Overall,
      government subsidized health insurance type arrangements can be effective
      mechanism to help countries progress towards UHC, yet there is potential to
      improve on institutional design features as well as implementation.

PMID- 27716305
TI  - Health seeking behavior and use of medicinal plants among the Hamer ethnic group,
      South Omo zone, southwestern Ethiopia.
AB  - BACKGROUND: Health seeking behavior of people around the globe is affected by
      different socio-cultural and economic factors. In Ethiopia, people living in
      rural areas in particular, are noted for their use of medicinal plants as a major
      component of their health care option. This study was conducted to document
      ethnopharmacological information of the Hamer semi-pastoralists ethnic group in
      southwestern Ethiopia. METHODS: A cross-sectional study was carried out whereby
      information on demographic characteristics, prevalence of perceived illnesses,
      factors associated with preference of health care seeking options, medicinal
      plants used and hoarded as well as some healers' socio-economic characteristics
      were collected using two sets of semi-structured questionnaires - one for
      household (HH) heads and the other for traditional healers supplemented by focus
      group discussions (FGDs). Households were selected using a cluster sampling
      followed by systematic sampling techniques; whereas healers and FGD participants
      were purposively selected with the assistance of local leaders and elders from
      the community. RESULTS: The study revealed that the use of traditional medicine
      among the Hamer ethnic group is very high. Females preferred traditional medicine
      more than males. The main reasons for this preference include effectiveness, low
      cost and ease of availability. Malaria (gebeze) was the most frequently occurring
      illness in the area identified by all FGD participants. A total of 60 different
      medicinal plants were reported [34 by HH respondents, 14 by traditional healers
      and 12 by both]. Fifty-one medicinal plants were fully identified, 3 at generic
      level and 6 have not yet been identified. CONCLUSION: It can be concluded that
      traditional medical practices, particularly herbal aspect, is widely used by the
      Hamer ethnic group, although health seeking behavior of the community is affected
      by different socio-economic and cultural factors.

PMID- 27716304
TI  - Appropriate vitamin D loading regimen for patients with advanced lung cancer.
AB  - BACKGROUND: Most patients attending cancer clinics have hypovitaminosis D.
      Correcting or preventing this abnormal condition could mitigate the emotional and
      physical complications of their disease, but clinical trials of vitamin D therapy
      in this setting are hindered by the unavailability of safe, effective and
      practical loading dose regimens. METHODS: In this single arm open-label
      pharmacokinetic trial, outpatients with advanced lung cancer consumed 20,000 IU
      vitamin D daily with the largest meal of the day for 14 days followed by 10,000
      IU per day for a further 7 days. Plasma concentrations of 25-hydroxyvitamin D
      [25(OH)D], parathyroid hormone, calcium, vitamin C and C-reactive protein were
      measured on protocol days 0, 14 and 21, and serum vitamin D binding protein
      (VDBP) concentrations on days 0 and 21. As a secondary objective, preliminary
      information was obtained regarding clinical effects of rapid vitamin D loading on
      mood and symptoms by administering appropriate questionnaires two times at
      baseline and after 14 and 21 days of vitamin D therapy. RESULTS: Of the 91
      patients enrolled in the study, 85 % had hypovitaminosis D and 41 % had
      hypovitaminosis C. Plasma VDBP concentrations were in the normal range. The
      vitamin D load increased the average plasma 25(OH)D concentration to 116 +/- 34
      nmol/L (mean +/- SD); the median concentration was 122 nmol/L (interquartile
      range 103-134); VDBP concentrations did not change. Final plasma 25(OH)D
      concentrations were subnormal (<75 nmol/L) for 13 % of the patients and sub
      target (<120 nmol/L) for 44 % of them. In most cases, subnormal and sub-target
      25(OH)D concentrations were attributable to obesity and/or a low baseline 25(OH)D
      concentration. Mood and symptom scores did not change significantly throughout
      the 3-week protocol. CONCLUSION: Hypovitaminosis D and C are very common in
      outpatients with advanced lung cancer. A vitamin D load of 20,000 IU per day for
      14 days failed to achieve the target concentration in 44 % of the participants in
      this trial. These results suggest that a loading dose of 30,000 IU per day for 14
      days would be safe and effective for patients who are obese or at risk of severe
      hypovitaminosis D. The preliminary nature of the study design, and the failure to
      achieve target 25(OH)D concentrations for a large proportion of the patients, do
      not allow any firm conclusion about the clinical effects of correcting
      hypovitaminosis D in this patient population. Nevertheless, no evidence was
      obtained that partial correction of hypovitaminosis D greatly improved mood,
      reduced distress or relieved cancer-related symptoms. This trial was registered
      at clinicaltrials.gov as NCT01631526.

PMID- 27716306
TI  - Post-incisional ventral hernia repair in patients undergoing chemotherapy:
      improving outcomes with biological mesh.
AB  - BACKGROUND: Patients requiring ventral hernia (VH) repair during perioperative
      chemotherapy have a higher risk for post-operative complications. The aim of the
      study was to perform a case-controlled analysis in patients undergoing
      chemotherapy who underwent VH repair using biological mesh or synthetic mesh.
      METHODS: From January 2013 to December 2015, 32 patients, within 8 weeks from
      chemotherapy administration, were treated electively for VH repair using a
      biological mesh (BIOMESH). A control group (CG) receiving chemotherapy within the
      same time interval and treated with synthetic meshes was selected. There were no
      differences regarding sex, age, American Society of Anesthesiologists (ASA) score
      III, BMI, and size of the defect. Morbidity, type of complications, and
      recurrence rate were investigated and compared between the two groups. RESULTS:
      In the BIOMESH group, eight patients (25 %) experienced complications. Wound
      dehiscence occurred in four (12.5 %) patients and was treated conservatively.
      Only three small seromas not requiring treatment were observed. The CG presented
      a higher mean Clavien-Dindo complication grade (1.94 +/- 0.44 vs 1.63 +/- 0.52; p
      = 0.13) and a higher incidence of wound dehiscence (n = 9/32, 28.1 % vs n = 4/32,
      12.5 %; p = 0.11). Five patients developed seroma treated by wound drainage. One
      patient experienced an intra-abdominal collection treated by percutaneous
      drainage. At the univariate and multivariate analysis use of traditional mesh,
      BMI and the ASA III were predictive factors of post-operative complications. Two
      patients (6.3 %) developed a VH recurrence only in the CG. CONCLUSIONS:
      Biological meshes could be considered a valid option to improve post-operative
      short-term outcomes in selected high-risk patients undergoing chemotherapy
      treated for VH repair.

PMID- 27716307
TI  - Lambda Red recombinase-mediated integration of the high molecular weight DNA into
      the Escherichia coli chromosome.
AB  - BACKGROUND: Escherichia coli K-12 is a frequently used host for a number of
      synthetic biology and biotechnology applications and chassis for the development
      of the minimal cell factories. Novel approaches for integrating high molecular
      weight DNA into the E. coli chromosome would therefore greatly facilitate
      engineering efforts in this bacterium. RESULTS: We developed a reliable and
      flexible lambda Red recombinase-based system, which utilizes overlapping DNA
      fragments for integration of the high molecular weight DNA into the E. coli
      chromosome. Our chromosomal integration strategy can be used to integrate high
      molecular weight DNA of variable length into any non-essential locus in the E.
      coli chromosome. Using this approach we integrated 15 kb DNA encoding sucrose
      catabolism and lactose metabolism and transport operons into the fliK locus of
      the flagellar region 3b in the E. coli K12 MG1655 chromosome. Furthermore, with
      this system we integrated 50 kb of Bacillus subtilis 168 DNA into two target
      sites in the E. coli K12 MG1655 chromosome. The chromosomal integrations into the
      fliK locus occurred with high efficiency, inhibited motility, and did not have a
      negative effect on the growth of E. coli. CONCLUSIONS: In addition to the
      rational design of synthetic biology devices, our high molecular weight DNA
      chromosomal integration system will facilitate metabolic and genome-scale
      engineering of E. coli.

PMID- 27716308
TI  - Compensation Research Database: population-based injury data for surveillance,
      linkage and mining.
AB  - BACKGROUND: Compensation health research aims to study the influence of
      compensation systems, processes and practices on health and health-related
      outcomes. In many jurisdictions, injury compensation authorities collect
      substantial volumes of case and service level data for the purpose of
      administering the compensation system. An important secondary use of such data is
      research and analysis to explore interactions between individuals and
      organisations in compensation systems, and between compensation and other systems
      including healthcare and legal systems, in order to understand the role of
      compensation processes in injury recovery. RESULTS: The Compensation Research
      Database (CRD) established at the Institute for Safety Compensation and Recovery
      Research at Monash University, holds over 20 years of population-based data for
      transport and workplace injury in the state of Victoria, Australia. The CRD is
      unique in that it is held independently, at arm's length from the compensation
      authorities that collect the data, and its primary purpose is to support research
      and analyses to develop new insights into system and individual level outcomes.
      This paper describes the core elements of the database including the design,
      process and type of information collected. We review some of the research
      findings that have been published using the CRD, and describe the ongoing program
      of research utilising the database. CONCLUSIONS: The CRD is a unique
      administrative database that supports research into compensation health, with the
      objective of improving understanding of the interaction between injury
      compensation systems and injury recovery. The availability of the CRD for
      independent research is leading to substantial advancements in the compensation
      health research field and in related areas.

PMID- 27716311
TI  - Novel mammographic image features differentiate between interval and screen
      detected breast cancer: a case-case study.
AB  - BACKGROUND: Interval breast cancers are often diagnosed at a more advanced stage
      than screen-detected cancers. Our aim was to identify features in screening
      mammograms of the normal breast that would differentiate between future interval
      cancers and screen-detected cancers, and to understand how each feature affects
      tumor detectability. METHODS: From a population-based cohort of invasive breast
      cancer cases in Stockholm-Gotland, Sweden, diagnosed from 2001 to 2008, we
      analyzed the contralateral mammogram at the preceding negative screening of 394
      interval cancer cases and 1009 screen-detected cancers. We examined 32 different
      image features in digitized film mammograms, based on three alternative dense
      area identification methods, by a set of logistic regression models adjusted for
      percent density with interval cancer versus screen-detected cancer as the
      outcome. Features were forward-selected into a multiple logistic regression model
      adjusted for mammographic percent density, age, BMI and use of hormone
      replacement therapy. The associations of the identified features were assessed
      also in a sample from an independent cohort. RESULTS: Two image features,
      'skewness of the intensity gradient' and 'eccentricity', were associated with the
      risk of interval compared with screen-detected cancer. For the first feature, the
      per-standard deviation odds ratios were 1.32 (95 % CI: 1.12 to 1.56) and 1.21 (95
      % CI: 1.04 to 1.41) in the primary and validation cohort respectively. For the
      second feature, they were 1.20 (95 % CI: 1.04 to 1.39) and 1.17 (95%CI: 0.98 to
      1.39) respectively. The first feature was associated with the tumor size at
      screen detection, while the second feature was associated with the tumor size at
      interval detection. CONCLUSIONS: We identified two novel mammographic features in
      screening mammograms of the normal breast that differentiated between future
      interval cancers and screen-detected cancers. We present a starting point for
      further research into features beyond percent density that might be relevant for
      interval cancer, and suggest ways to use this information to improve screening.

PMID- 27716309
TI  - Correlation of an epigenetic mitotic clock with cancer risk.
AB  - BACKGROUND: Variation in cancer risk among somatic tissues has been attributed to
      variations in the underlying rate of stem cell division. For a given tissue type,
      variable cancer risk between individuals is thought to be influenced by extrinsic
      factors which modulate this rate of stem cell division. To date, no molecular
      mitotic clock has been developed to approximate the number of stem cell divisions
      in a tissue of an individual and which is correlated with cancer risk. RESULTS:
      Here, we integrate mathematical modeling with prior biological knowledge to
      construct a DNA methylation-based age-correlative model which approximates a
      mitotic clock in both normal and cancer tissue. By focusing on promoter CpG sites
      that localize to Polycomb group target genes that are unmethylated in 11
      different fetal tissue types, we show that increases in DNA methylation at these
      sites defines a tick rate which correlates with the estimated rate of stem cell
      division in normal tissues. Using matched DNA methylation and RNA-seq data, we
      further show that it correlates with an expression-based mitotic index in cancer
      tissue. We demonstrate that this mitotic-like clock is universally accelerated in
      cancer, including pre-cancerous lesions, and that it is also accelerated in
      normal epithelial cells exposed to a major carcinogen. CONCLUSIONS: Unlike other
      epigenetic and mutational clocks or the telomere clock, the epigenetic clock
      proposed here provides a concrete example of a mitotic-like clock which is
      universally accelerated in cancer and precancerous lesions.

PMID- 27716312
TI  - Characterizing physical activity and food urban environments: a GIS-based
      multicomponent proposal.
AB  - BACKGROUND: Healthier urban environments influence the distribution of
      cardiovascular risk factors. Our aim was to design and implement a multicomponent
      method based on Geographic Information Systems to characterize and evaluate
      environmental correlates of obesity: the food and the physical activity urban
      environments. METHODS: Study location comprised a socio-demographically average
      urban area of 12 contiguous census sections (~16,000 residents), in Madrid,
      Spain. We conducted on-field audits on all food stores and street segments. We
      designed a synthetic index integrating continuous measures of both environments,
      by kernel density analyses. Index ranges from 0 to 100 (least-most healthy).
      RESULTS: We found a heterogeneous distribution with 75 and 50 % of the area
      scoring less than 36.8 and 25.5, respectively. Census sections of study area were
      categorized by Jenks intervals as high, medium-high, medium-low and low. 41.0 %
      of residents lived in an area with a low score, 23.6 % medium-low and 31.1 %
      medium-high and 4.2 % in a high. CONCLUSION: The proposed synthetic index may be
      a relevant tool to inform urban health interventions, providing a feasible way to
      integrate different measures of barriers and facilitators of healthy urban
      environments in terms of food and physical activity.

PMID- 27716310
TI  - Hyperchloremia and moderate increase in serum chloride are associated with acute
      kidney injury in severe sepsis and septic shock patients.
AB  - BACKGROUND: Acute kidney injury and hyperchloremia are commonly present in
      critically ill septic patients. Our study goal was to evaluate the association of
      hyperchloremia and acute kidney injury in severe sepsis and septic shock
      patients. METHODS: In this retrospective cohort study in a provincial tertiary
      care hospital, adult patients with severe sepsis or septic shock and serum
      chloride measurements were included. Serum chloride was measured on a daily basis
      for 48 hours. Primary outcome was development of acute kidney injury (AKI) and
      association of AKI and serum chloride parameters was analyzed. RESULTS: A total
      of 240 patients were included in the study, 98 patients (40.8 %) had
      hyperchloremia. The incidence of acute kidney injury (AKI) was significantly
      higher in the hyperchloremia group (85.7 % vs 47.9 %; p < 0.001). Maximal
      chloride concentration in the first 48 hours ([Cl-]max) was significantly
      associated with AKI. In multivariate analysis, [Cl-]max was independently
      associated with AKI [adjusted odds ratio (OR) for AKI = 1.28 (1.02-1.62); p =
      0.037]. The increase in serum chloride (Delta[Cl-] = [Cl-]max - initial chloride
      concentration) demonstrated a dose-dependent relationship with severity of AKI.
      The mean Delta[Cl-] in patients without AKI was 2.1 mmol/L while in the patients
      with AKI stage 1, 2 and 3 the mean Delta[Cl-] was 5.1, 5.9 and 6.7 mmol/L,
      respectively. A moderate increase in serum chloride (Delta[Cl-] >= 5 mmol/L) was
      associated with AKI [OR = 5.70 (3.00-10.82); p < 0.001], even in patients without
      hyperchloremia [OR = 8.25 (3.44-19.78); p < 0.001]. CONCLUSIONS: Hyperchloremia
      is common in severe sepsis and septic shock and independently associated with
      AKI. A moderate increase in serum chloride (Delta[Cl-] >=5 mmol/L) is associated
      with AKI even in patients without hyperchloremia.

PMID- 27716313
TI  - Supportive supervision for volunteers to deliver reproductive health education: a
      cluster randomized trial.
AB  - BACKGROUND: Community Health Volunteers (CHVs) can be effective in improving
      pregnancy and newborn outcomes through community education. Inadequate
      supervision of CHVs, whether due to poor planning, irregular visits, or
      ineffective supervisory methods, is, however, recognized as a weakness in many
      programs. There has been little research on best practice supervisory or
      accompaniment models. METHODS: From March 2014 to February 2015 a proof of
      concept study was conducted to compare training alone versus training and
      supportive supervision by paid CHWs (n = 4) on the effectiveness of CHVs (n = 82)
      to deliver education about pregnancy, newborn care, family planning and hygiene.
      The pair-matched cluster randomized trial was conducted in eight villages (four
      intervention and four control) in Budondo sub-county in Jinja, Uganda. RESULTS:
      Increases in desired behaviors were seen in both the intervention and control
      arms over the study period. Both arms showed high retention rates of CHVs (95 %).
      At 1 year follow-up there was a significantly higher prevalence of installed and
      functioning tippy taps for hand washing (p < 0.002) in the intervention villages
      (47 %) than control villages (35 %). All outcome and process measures related to
      home-visits to homes with pregnant women and newborn babies favored the
      intervention villages. The CHVs in both groups implemented what they learnt and
      were role models in the community. CONCLUSIONS: A team of CHVs and CHWs can
      facilitate families accessing reproductive health care by addressing cultural
      norms and scientific misconceptions. Having a team of 2 CHWs to 40 CHVs enables
      close to community access to information, conversation and services. Supportive
      supervision involves creating a non-threatening, empowering environment in which
      both the CHV and the supervising CHW learn together and overcome obstacles that
      might otherwise demotivate the CHV. While the results seem promising for added
      value with supportive supervision for CHVs undertaking reproductive health
      activities, further research on a larger scale will be needed to substantiate the
      effect.

PMID- 27716314
TI  - Lipid nanoemulsions and liposomes improve photodynamic treatment efficacy and
      tolerance in CAL-33 tumor bearing nude mice.
AB  - BACKGROUND: Photodynamic therapy (PDT) as promising alternative to conventional
      cancer treatments works by irradiation of a photosensitizer (PS) with light,
      which creates reactive oxygen species and singlet oxygen (1O2), that damage the
      tumor. However, a routine use is hindered by the PS's poor water solubility and
      extended cutaneous photosensitivity of patients after treatment. In our study we
      sought to overcome these limitations by encapsulation of the PS m
      tetrahydroxyphenylchlorin (mTHPC) into a biocompatible nanoemulsion (Lipidots).
      RESULTS: In CAL-33 tumor bearing nude mice we compared the Lipidots to the
      existing liposomal mTHPC nanoformulation Foslip and the approved mTHPC
      formulation Foscan. We established biodistribution profiles via fluorescence
      measurements in vivo and high performance liquid chromatography (HPLC) analysis.
      All formulations accumulated in the tumors and we could determine the optimum
      treatment time point for each substance (8 h for mTHPC, 24 h for Foslip and 72 h
      for the Lipidots). We used two different light doses (10  and 20 J/cm2) and
      evaluated immediate PDT effects 48 h after treatment and long term effects 14
      days later. We also analyzed tumors by histological analysis and performing
      reverse transcription real-time PCR with RNA extracts. Concerning tumor
      destruction Foslip was superior to Lipidots and Foscan while with regard to
      tolerance and side effects Lipidots were giving the best results. CONCLUSIONS: We
      could demonstrate in our study that nanoformulations are superior to the free PS
      mTHPC. The development of a potent nanoformulation is of major importance because
      the free PS is related to several issues such as poor bioavailability, solubility
      and increased photosensibility of patients. We could show in this study that
      Foslip is very potent in destroying the tumors itself. However, because the
      Lipidots' biocompatibility is outstanding and superior to the liposomes we plan
      to carry out further investigations and protocol optimization. Both
      nanoformulations show great potential to revolutionize PDT in the future.

PMID- 27716316
TI  - Ultrasonographic assessment of bone erosions in the different subtypes of
      systemic lupus erythematosus arthritis: comparison with computed tomography.
AB  - BACKGROUND: The aim was to determine the accuracy of high-resolution
      ultrasonography (US) for detecting erosion in the metacarpophalangeal (MCP) and
      wrist joints of patients with different subtypes of systemic lupus erythematosus
      (SLE) arthritis, using computed tomography (CT) as the gold-standard reference
      method. METHOD: The ulnar head, radiocarpal and second to fifth MCP joints in 26
      patients with SLE - 9 classified as having rhupus syndrome, 10 as having
      Jaccoud's arthropathy (JA) and 7 as having non-deforming non-erosive (NDNE)
      arthritis - were subdivided into areas and bilaterally evaluated for the presence
      of bone erosion by CT and US. On CT, erosion volume was scored according to the
      outcome measures in rheumatology-rheumatoid arthritis magnetic resonance imaging
      (OMERACT-RAMRIS) score. On US, erosions were semi-quantitatively scored 0-3
      according to scoring by ultrasound structural erosion (ScUSSe) systems. RESULTS:
      Erosions were detected by CT in 92/728 areas (12.6 %) and by US in 43/728 areas
      (5.9 %). Sensitivity, specificity and accuracy of US overall was 36 %, 98 % and
      90 % compared with 57 %, 98 % and 93 % in the dorsal and lateral aspects of the
      second and fifth MCP, which were identified as areas with the best US
      reliability. Adding wrist joints would capture a larger number of erosions
      without affecting the accuracy. US detected 90.0 % of CT erosions with bone
      volume loss >20 % and 51.2 % of erosions with bone volume loss >10 %. Patients
      with rhupus had a greater number of larger erosions than those with JA or NDNE
      arthritis, with prevalent involvement of the MCP joints. Overall reliability of
      US in detecting bone erosions was moderate for rhupus syndrome (0.55) and JA
      (0.58), but poor for NDNE arthritis (0.10). CONCLUSION: US had moderate
      sensitivity and excellent specificity for detection and semi-quantitative
      assessment of bone erosions in SLE.

PMID- 27716315
TI  - Comparison of supraintercondylar and supracondylar femur fractures treated with
      condylar buttress plates.
AB  - BACKGROUND: Treatment of supraintercondylar (AO/OTA 33-C) and supracondylar
      (AO/OTA 33-A) femur fractures is generally challenging. Standard treatments
      include open reduction and internal fixation. However, optimal implants are now
      being well-defined. This study focus on the comparison between clinical and
      functional outcomes of fractures treated with condylar buttress plates (CBPs).
      METHODS: We treated 87 patients with supraintercondylar or supracondylar femur
      fracture from 2004 to 2008, including 30 supraintercondylar and 24 supracondylar
      fractures treated with CBPs. Both knee and function scores (per Knee Society)
      were given to clinical and functional outcomes, and concomitant knee function was
      assessed per Mize criteria. RESULTS: Union rate of supraintercondylar fractures
      was 90 % (27/30) and supracondylar fractures was 91.7 % (22/24) (P = 0.68). In
      supraintercondylar group, 16.7 % revealed postoperative varus deformity, whereas
      none in supracondylar group (P = 0.045). Knee Society knee score was 73.6 in
      supraintercondylar group and 85.5 in supracondylar group (P = 0.009); and
      function score was 62.5 in supraintercondylar group and 83.1 in supracondylar
      group (P = 0.023). A satisfactory result based on modified Mize criteria was
      achieved in 50 % of supraintercondylar fractures and in 79.1 % of supracondylar
      fractures (P = 0.09). CONCLUSIONS: Use of CBPs for supraintercondylar and
      supracondylar femur fractures treatment led to a high union rate. However, a high
      rate of varus deformity occurred in patients with supraintercondylar but not
      supracondylar fractures. Moreover, CBP treatment in patients with supracondylar
      fractures led to better functional outcomes than those with supraintercondylar
      fractures.

PMID- 27716317
TI  - Why hospital physicians attend work while ill? The spiralling effect of positive
      and negative factors.
AB  - BACKGROUND: Recurrent reports from national and international studies show a
      persistent high prevalence of sickness presence among hospital physicians.
      Despite the negative consequences reported, we do not know a lot about the
      reasons why physicians choose to work when ill, and whether there may be some
      positive correlates of this behaviour that in turn may lead to the design of
      appropriate interventions. The aim of this study is to explore the perception and
      experience with sickness presenteeism among hospital physicians, and to explore
      possible positive and negative foundations and consequences associated with
      sickness presence. METHODS: Semi-structured interviews of 21 Norwegian university
      hospital physicians. RESULTS: Positive and negative dimensions associated with 1)
      evaluation of illness, 2) organizational structure, 3) organizational culture,
      and 4) individual factors simultaneously contributed to presenteeism.
      CONCLUSIONS: The study underlines the inherent complexity of the causal chain of
      events affecting sickness presenteeism, something that also inhibits
      intervention. It appears that sufficient staffing, predictability in employment,
      adequate communication of formal policies and senior physicians adopting the
      position of a positive role model are particularly important.

PMID- 27716318
TI  - Reliability and validity of the Chinese mandarin version of PedsQLTM 3.0
      transplant module.
AB  - BACKGROUND: Long-term health-related quality of life (HRQoL) of pediatric
      patients after hematopoietic stem cell transplantation (HSCT) is increasingly
      studied worldwide. However, few studies have been performed in China, where no
      uniform scale is available; the PedsQLTM Cancer Module 3.0 Chinese Mandarin
      version has been used to evaluate HRQoL of patients after HSCT in China. This
      study aimed to assess the reliability and validity of the Chinese Mandarin
      version of PedsQLTM 3.0 Transplant Module. METHODS: Patients between 2 and 18
      years old, who underwent HSCT from January 2006 to June 2014, were recruited in
      Beijing Children's Hospital affiliated to Capital Medical University, the First
      Affiliated Hospital of Southern Medical University and Beijing Daopei Hospital.
      207 parent reports and 182 child self-reports of the PedsQLTM 3.0 Transplant
      Module Chinese Mandarin version were assigned, of which 362 were returned.
      RESULTS: No missing item response was observed in the returned reports.
      Cronbach's alpha coefficient exceeded 0.7 in total scale and every dimension. The
      intraclass correlation coefficient exceeded 0.8 in all dimensions of child self
      reports and parent reports. Spearman's rank correlation coefficients of items and
      their respective dimensions were 0.6-0.94 in parent reports, and 0.62-0.93 in
      child self-reports, while a weak association was found between the items and
      other dimensions. Exploratory factor analysis indicated a good extraction effect,
      and construct validity of the scale was >60 %. CONCLUSIONS: The Chinese Mandarin
      version of PedsQLTM 3.0 Transplant Module has good feasibility, reliability and
      validity. Its use may help improve the HRQoL of children after HSCT in China.

PMID- 27716319
TI  - Local spatial variations analysis of smear-positive tuberculosis in Xinjiang
      using Geographically Weighted Regression model.
AB  - BACKGROUND: The spatial interplay between socioeconomic factors and tuberculosis
      (TB) cases contributes to the understanding of regional tuberculosis burdens.
      Historically, local Poisson Geographically Weighted Regression (GWR) has allowed
      for the identification of the geographic disparities of TB cases and their
      relevant socioeconomic determinants, thereby forecasting local regression
      coefficients for the relations between the incidence of TB and its socioeconomic
      determinants. Therefore, the aims of this study were to: (1) identify the
      socioeconomic determinants of geographic disparities of smear positive TB in
      Xinjiang, China (2) confirm if the incidence of smear positive TB and its
      associated socioeconomic determinants demonstrate spatial variability (3) compare
      the performance of two main models: one is Ordinary Least Square Regression
      (OLS), and the other local GWR model. METHODS: Reported smear-positive TB cases
      in Xinjiang were extracted from the TB surveillance system database during 2004
      2010. The average number of smear-positive TB cases notified in Xinjiang was
      collected from 98 districts/counties. The population density (POPden), proportion
      of minorities (PROmin), number of infectious disease network reporting agencies
      (NUMagen), proportion of agricultural population (PROagr), and per capita annual
      gross domestic product (per capita GDP) were gathered from the Xinjiang
      Statistical Yearbook covering a period from 2004 to 2010. The OLS model and GWR
      model were then utilized to investigate socioeconomic determinants of smear
      positive TB cases. Geoda 1.6.7, and GWR 4.0 software were used for data analysis.
      RESULTS: Our findings indicate that the relations between the average number of
      smear-positive TB cases notified in Xinjiang and their socioeconomic determinants
      (POPden, PROmin, NUMagen, PROagr, and per capita GDP) were significantly
      spatially non-stationary. This means that in some areas more smear-positive TB
      cases could be related to higher socioeconomic determinant regression
      coefficients, but in some areas more smear-positive TB cases were found to do
      with lower socioeconomic determinant regression coefficients. We also found out
      that the GWR model could be better exploited to geographically differentiate the
      relationships between the average number of smear-positive TB cases and their
      socioeconomic determinants, which could interpret the dataset better (adjusted R
      2 = 0.912, AICc = 1107.22) than the OLS model (adjusted R 2 = 0.768, AICc =
      1196.74). CONCLUSIONS: POPden, PROmin, NUMagen, PROagr, and per capita GDP are
      socioeconomic determinants of smear-positive TB cases. Comprehending the spatial
      heterogeneity of POPden, PROmin, NUMagen, PROagr, per capita GDP, and smear
      positive TB cases could provide valuable information for TB precaution and
      control strategies.

PMID- 27716320
TI  - Bosentan and macitentan prevent the endothelial-to-mesenchymal transition
      (EndoMT) in systemic sclerosis: in vitro study.
AB  - BACKGROUND: Systemic sclerosis (SSc) is characterized by early vascular
      abnormalities and subsequent fibroblast activation to myofibroblasts, leading to
      fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex
      biological process in which endothelial cells lose their specific markers and
      acquire a mesenchymal or myofibroblastic phenotype, has been reported in SSc. In
      the present study, we evaluated the ability of endothelin-1 (ET-1) dual receptor
      antagonists bosentan (BOS) and macitentan (MAC) to antagonize EndoMT in vitro.
      METHODS: Ten women with limited SSc were enrolled. They underwent double skin
      biopsy (affected and nonaffected skin). Fibroblasts and microvascular endothelial
      cells (MVECs) were isolated from biopsies. We performed mono- or coculture of
      MVECs (isolated from nonaffected skin) with fibroblasts (isolated from affected
      skin and stimulated with ET-1 and transforming growth factor beta [TGF-beta]). In
      cocultures, the MVEC layer was left undisturbed or was preincubated with BOS or
      MAC. After 48 h of coculture, MVECs were analyzed for their tube formation
      ability and for messenger RNA and protein expression of different vascular (CD31,
      vascular endothelial growth factor-A [VEGF-A], VEGF-A165b) and profibrotic (alpha
      smooth muscle actin [alpha-SMA], collagen type I [Col I], TGF-beta) molecules.
      RESULTS: After 48 h, MVECs showed a reduced tube formation ability when
      cocultured with SSc fibroblasts. CD31 and VEGF-A resulted in downregulation,
      while VEGF-A165b, the antiangiogenic isoform, resulted in upregulation. At the
      same time, mesenchymal markers alpha-SMA, Col I, and TGF-beta resulted in
      overexpression in MVECs. Tube formation ability was restored when MVECs were
      preincubated with BOS or MAC, also reducing the expression of mesenchymal markers
      and restoring CD31 expression and the imbalance between VEGF-A and VEGF-A165b.
      CONCLUSIONS: With this innovative EndoMT in vitro model realized by coculturing
      nonaffected MVECs with affected SSc fibroblasts, we show that the presence of a
      myofibroblast phenotype in the fibroblast layer, coupled with an ET-1-TGF-beta
      synergic effect, is responsible for EndoMT. BOS and MAC seem able to antagonize
      this phenomenon in vitro, confirming previous evidence of endothelium-derived
      fibrosis in SSc and possible pharmacological interference.

PMID- 27716321
TI  - Blood pulsation measurement using cameras operating in visible light:
      limitations.
AB  - BACKGROUND: The paper presents an automatic method for analysis and processing of
      images from a camera operating in visible light. This analysis applies to images
      containing the human facial area (body) and enables to measure the blood pulse
      rate. Special attention was paid to the limitations of this measurement method
      taking into account the possibility of using consumer cameras in real conditions
      (different types of lighting, different camera resolution, camera movement).
      METHODS: The proposed new method of image analysis and processing was associated
      with three stages: (1) image pre-processing-allowing for the image filtration and
      stabilization (object location tracking); (2) main image processing-allowing for
      segmentation of human skin areas, acquisition of brightness changes; (3) signal
      analysis-filtration, FFT (Fast Fourier Transformation) analysis, pulse
      calculation. RESULTS AND CONCLUSIONS: The presented algorithm and method for
      measuring the pulse rate has the following advantages: (1) it allows for non
      contact and non-invasive measurement; (2) it can be carried out using almost any
      camera, including webcams; (3) it enables to track the object on the stage, which
      allows for the measurement of the heart rate when the patient is moving; (4) for
      a minimum of 40,000 pixels, it provides a measurement error of less than +/-2
      beats per minute for p < 0.01 and sunlight, or a slightly larger error (+/-3
      beats per minute) for artificial lighting; (5) analysis of a single image takes
      about 40 ms in Matlab Version 7.11.0.584 (R2010b) with Image Processing Toolbox
      Version 7.1 (R2010b).

PMID- 27716322
TI  - Spatial analysis and characteristics of pig farming in Thailand.
AB  - BACKGROUND: In Thailand, pig production intensified significantly during the last
      decade, with many economic, epidemiological and environmental implications.
      Strategies toward more sustainable future developments are currently
      investigated, and these could be informed by a detailed assessment of the main
      trends in the pig sector, and on how different production systems are
      geographically distributed. This study had two main objectives. First, we aimed
      to describe the main trends and geographic patterns of pig production systems in
      Thailand in terms of pig type (native, breeding, and fattening pigs), farm scales
      (smallholder and large-scale farming systems) and type of farming systems (farrow
      to-finish, nursery, and finishing systems) based on a very detailed 2010 census.
      Second, we aimed to study the statistical spatial association between these
      different types of pig farming distribution and a set of spatial variables
      describing access to feed and markets. RESULTS: Over the last decades, pig
      population gradually increased, with a continuously increasing number of pigs per
      holder, suggesting a continuing intensification of the sector. The different pig
      production systems showed very contrasted geographical distributions. The spatial
      distribution of large-scale pig farms corresponds with that of commercial pig
      breeds, and spatial analysis conducted using Random Forest distribution models
      indicated that these were concentrated in lowland urban or peri-urban areas,
      close to means of transportation, facilitating supply to major markets such as
      provincial capitals and the Bangkok Metropolitan region. Conversely the
      smallholders were distributed throughout the country, with higher densities
      located in highland, remote, and rural areas, where they supply local rural
      markets. A limitation of the study was that pig farming systems were defined from
      the number of animals per farm, resulting in their possible misclassification,
      but this should have a limited impact on the main patterns revealed by the
      analysis. CONCLUSIONS: The very contrasted distribution of different pig
      production systems present opportunities for future regionalization of pig
      production. More specifically, the detailed geographical analysis of the
      different production systems will be used to spatially-inform planning decisions
      for pig farming accounting for the specific health, environment and economical
      implications of the different pig production systems.

PMID- 27716323
TI  - Precise film dosimetry for stereotactic radiosurgery and stereotactic body
      radiotherapy quality assurance using GafchromicTM EBT3 films.
AB  - PURPOSE: The purpose of this study is to evaluate the dosimetric uncertainty
      associated with GafchromicTM (EBT3) films and establish a practical and efficient
      film dosimetry protocol for Stereotactic Radiosurgery (SRS) and Stereotactic Body
      Radiotherapy (SBRT). METHOD AND MATERIALS: EBT3 films were irradiated at each of
      seven different dose levels between 1 and 15 Gy with open fields and standard
      deviations of dose maps were calculated at each color channel for evaluation. A
      scanner non-uniform response correction map was built by registering and
      comparing film doses to the reference ion chamber array-based dose map delivered
      with the same doses. To determine the temporal dependence of EBT3 films, the
      average correction factors of different dose levels as a function of time were
      evaluated up to 4 days after irradiation. An integrated film dosimetry protocol
      was developed for dose calibration, calibration curve fitting, dose mapping, and
      profile/gamma analysis. Patient specific quality assurance (PSQA) was performed
      for 83 SRS/SBRT treatment plans, and analysis of the measurements and
      calculations are presented here. RESULTS: The scanner response varied within 1 %
      for the field sizes less than 5 * 5 cm2, and up to 5 % for the field sizes of 10
      * 10 cm2 for all color channels. The scanner correction method was able to remove
      visually evident, irregular detector responses for larger field sizes. The dose
      response of the film changed rapidly (~10 %) in the first two hours and became
      smooth plateaued afterwards, ~3 % change between 2 and 24 h. The uncertainties
      were approximately 1.5, 1.7 and 4.8 % over the dose range of 3~15 Gy for the red,
      green and blue channels. The green channel showed very high sensitivity and low
      uncertainty in the dose range between 10 and 15 Gy, which is suitable for
      SRS/SBRT commissioning and PSQA. The difference between the calculated dose and
      measured dose of ion chamber measurement at isocenter was -0.64 +/- 2.02 for all
      plans, corresponding to a 95 % confidence interval of (-1.09, -0.26). The
      percentage of points passing the 3 %/1 mm gamma criteria in absolute dose,
      averaged over all tests was 95.0 +/- 4.2. CONCLUSION: We have developed the EBT3
      films based dosimetry protocol to obtain absolute dose values. The overall
      uncertainty has been established to be 1.5 % for SRS and SBRT PSQA.

PMID- 27716324
TI  - Sarilumab plus methotrexate suppresses circulating biomarkers of bone resorption
      and synovial damage in patients with rheumatoid arthritis and inadequate response
      to methotrexate: a biomarker study of MOBILITY.
AB  - BACKGROUND: Interleukin 6 (IL-6) signaling plays a key role in the
      pathophysiology of rheumatoid arthritis (RA) and is inhibited by sarilumab, a
      human monoclonal antibody blocking the IL-6 receptor alpha (IL-6Ralpha). The
      effects of sarilumab plus methotrexate (MTX) on serum biomarkers of joint damage
      and bone resorption were assessed in two independent studies (phase II (part A)
      and phase III (part B)) of patients with RA with a history of inadequate response
      to MTX from the MOBILITY study (NCT01061736). METHODS: Serum samples were
      analyzed at baseline and prespecified posttreatment time points. Biomarkers of
      tissue destruction, cartilage degradation, and synovial inflammation were
      measured in part A; assessment of these markers was repeated in part B and
      included additional analysis of biomarkers of bone formation and resorption
      (including soluble receptor activator of nuclear factor-kB ligand (sRANKL)). A
      mixed model for repeated measures was used to compare treatment effects on change
      in biomarkers. Additionally, changes from baseline in biomarkers were compared
      between American College of Rheumatology 50 % responders and nonresponders and
      between patients who achieved or did not achieve low disease activity (LDA),
      separately by treatment group, at week 24. RESULTS: In part A, sarilumab 150 and
      200 mg every 2 weeks (q2w) significantly reduced biomarkers of tissue
      destruction, cartilage degradation, and synovial inflammation at both 2 and 12
      weeks posttreatment (p < 0.05 vs placebo). These results were replicated in part
      B, with markers of these damaging processes reduced at weeks 2 and 24 (p < 0.05
      vs placebo). Additionally, sarilumab 200 mg q2w significantly reduced both sRANKL
      and sRANKL/osteoprotegerin ratio at week 24 (p < 0.01 vs placebo). Trends for
      reduction were noted for several biomarkers in patients who achieved LDA compared
      with those who did not. CONCLUSIONS: Sarilumab plus MTX significantly suppressed
      biomarkers of bone resorption and joint damage, as compared with placebo plus
      MTX, in patients with RA. Additional work is needed to determine whether
      differences in biomarker profiles at baseline or posttreatment can identify
      patients who achieve improvement in disease activity. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01061736 , February 2, 2010.

PMID- 27716325
TI  - A scoping review of Australian allied health research in ehealth.
AB  - BACKGROUND: Uptake of e-health, the use of information communication technologies
      (ICT) for health service delivery, in allied health appears to be lagging behind
      other health care areas, despite offering the potential to address problems with
      service access by rural and remote Australians. The aim of the study was to
      conduct a scoping review of studies into the application of or attitudes towards
      ehealth amongst allied health professionals conducted in Australia. METHODS:
      Studies meeting inclusion criteria published from January 2004 to June 2015 were
      reviewed. Professions included were audiology, dietetics, exercise physiology,
      occupational therapy, physiotherapy, podiatry, social work, and speech pathology.
      Terms for these professions and forms of ehealth were combined in databases of
      CINAHL (EBSCO), Cochrane Library, PsycINFO (1806 - Ovid), MEDLINE (Ovid) and AMED
      (Ovid). RESULTS: Forty-four studies meeting inclusion criteria were summarised.
      They were either trials of aspects of ehealth service delivery, or clinician
      and/or client use of and attitudes towards ehealth. Trials of ehealth were
      largely from two research groups located at the Universities of Sydney and
      Queensland; most involved speech pathology and physiotherapy. Assessments through
      ehealth and intervention outcomes through ehealth were comparable with face-to
      face delivery. Clinicians used ICT mostly for managing their work and for
      professional development, but were reticent about its use in service delivery,
      which contrasted with the more positive attitudes and experiences of clients.
      CONCLUSION: The potential of ehealth to address allied health needs of
      Australians living in rural and remote Australia appears unrealised. Clinicians
      may need to embrace ehealth as a means to radicalise practice, rather than
      replicate existing practices through a different mode of delivery.

PMID- 27716326
TI  - Physical activity throughout adolescence and body composition at 18 years: 1993
      Pelotas (Brazil) birth cohort study.
AB  - BACKGROUND: Adolescence is a period of accelerated development and increases in
      body composition. Physical activity (PA) practice has been associated with the
      development of major components of body composition (bone, muscle and fat).
      However, the longitudinal effects of PA of different intensities during
      adolescence are still not well understood. Thus, the main goal this study has
      investigate the association between practice of moderate- and vigorous-intensity
      physical activity throughout adolescence and body composition, specifically lean
      mass (LM) and fat mass (FM), at age 18. METHODS: In this cohort study, physical
      activity was measured at 11, 15 and 18 years, using questionnaires. Thresholds of
      300, 150 and 75 min per week, were used for MVPA, moderate- and vigorous
      intensity physical activity, respectively. Consistent physical activity was
      defined as reaching the thresholds at the three follow-ups. FM and LM at age 18
      were assessed by DXA and expressed as fat mass (FMI) and lean mass (LMI) indexes.
      To verify the association between the trajectories of MVPA, moderate- and
      vigorous-intensity physical activity in adolescence and FM and LM at 18,
      multivariate analyses were performed through multiple linear regressions adjusted
      for co-variables. RESULTS: A total of 3,176 adolescents were evaluated. The
      consistent practice of moderate- and vigorous-intensity physical activity
      according to thresholds during adolescence were directly related to the LMI in
      boys (moderate-intensity - beta = 0.40 and CI95 % 0.13; 0.68 and vigorous
      intensity - beta = 0.95 and CI95 % 0.69; 1.21) and girls (Moderate-intensity -
      beta = 0.23 and CI95 % 0.02; 0.45 and vigorous-intensity - beta = 0.80 and CI95 %
      0.29; 1.32). Practice of vigorous-intensity physical activity alone showed to be
      inversely associated with the FMI in boys (beta = -0.53 and CI95 % -0.96;-0.10).
      CONCLUSION: Consistent physical activity practice during adolescence was
      associated with greater lean mass in both sexes. In boys, vigorous-intensity
      physical activity was associated with less fat mass.

PMID- 27716328
TI  - Cardiorespiratory fitness: a comparison between children with renal
      transplantation and children with congenital solitary functioning kidney.
AB  - Children with end-stage renal disease are known to have a cardiorespiratory
      fitness significantly reduced. This is considered to be an independent index
      predictive of mortality mainly due to cardiovascular accidents. The effects of
      renal transplantation on cardiorespiratory fitness are incompletely known. We
      compared the maximal oxygen uptake (VO2 max) of children with a functioning renal
      transplant with that of children with congenital solitary functioning kidney,
      taking into consideration also the amount of weekly sport activity.

PMID- 27716327
TI  - Living together in biofilms: the microbial cell factory and its biotechnological
      implications.
AB  - In nature, bacteria alternate between two modes of growth: a unicellular life
      phase, in which the cells are free-swimming (planktonic), and a multicellular
      life phase, in which the cells are sessile and live in a biofilm, that can be
      defined as surface-associated microbial heterogeneous structures comprising
      different populations of microorganisms surrounded by a self-produced matrix that
      allows their attachment to inert or organic surfaces. While a unicellular life
      phase allows for bacterial dispersion and the colonization of new environments,
      biofilms allow sessile cells to live in a coordinated, more permanent manner that
      favors their proliferation. In this alternating cycle, bacteria accomplish two
      physiological transitions via differential gene expression: (i) from planktonic
      cells to sessile cells within a biofilm, and (ii) from sessile to detached, newly
      planktonic cells. Many of the innate characteristics of biofilm bacteria are of
      biotechnological interest, such as the synthesis of valuable compounds (e.g.,
      surfactants, ethanol) and the enhancement/processing of certain foods (e.g.,
      table olives). Understanding the ecology of biofilm formation will allow the
      design of systems that will facilitate making products of interest and improve
      their yields.

PMID- 27716329
TI  - Long noncoding RNA expression profile in fibroblast-like synoviocytes from
      patients with rheumatoid arthritis.
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) have recently received wide attention
      as key molecules that mediate a variety of physiological and pathological
      processes by regulating gene expression; however, knowledge of lncRNAs in
      rheumatoid arthritis (RA) is limited. Thus, we investigated the lncRNA expression
      profile in fibroblast-like synoviocytes (FLSs) from patients with RA and explored
      the function of abundantly expressed lncRNAs. METHODS: LncRNA and mRNA
      microarrays were performed to identify differentially expressed lncRNAs in RA
      FLSs compared with normal FLSs. Quantitative polymerase chain reaction (qPCR) was
      used to validate the results, and correlation analysis was used to analyze the
      relationship between these aberrantly expressed lncRNAs and clinical
      characteristics. A receiver operating characteristic (ROC) curve was constructed
      to evaluate the diagnostic value of the lncRNAs identified. RESULTS: According to
      the gene expression profiles, 135 lncRNAs were differentially expressed between
      RA and normal FLSs. Furthermore, qPCR data showed that lncRNA ENST00000483588 was
      up-regulated and that three lncRNAs (ENST00000438399, uc004afb.1, and
      ENST00000452247) were down-regulated in RA FLSs. The expression level of
      ENST00000483588 was positively correlated with the level of C-reactive protein
      and the Simplified Disease Activity Index score. Moreover, the areas under the
      ROC curve were 0.85, 0.92, 0.97, and 0.92 for ENST00000483588, ENST00000438399,
      uc004afb.1, and ENST00000452247, respectively. CONCLUSIONS: The results indicate
      that the dysregulation of ENST00000483588, ENST00000438399, uc004afb.1, and
      ENST00000452247 may be involved in the pathological processes of RA and that
      these lncRNAs may have potential value for the diagnosis and assessment of the
      disease activity of RA.

PMID- 27716331
TI  - Bedside PDA ligation in premature infants less than 28 weeks and 1000 grams.
AB  - BACKGROUND: PDA(Patent ductus arteriosus) is a common and clinically important
      condition which is presented with a number of hemodynamic and respiratory
      problems such as intraventricular hemorrhage, pulmonary hemorrhage and
      necrotizing enterocolitis due to increased pulmonary blood flow and stealing from
      systemic circulation. The incidence of PDA among the infants that were born
      before the 28th gestational week is as high as 70 %; and spontaneous closure
      rates in very-low-birth-weight premature neonates(VLBWPN) is around 34 %. The
      onset, duration, and repeat number of consecutive courses of the prostaglandin
      synthesis inhibitor medication for PDA closure are still issues of debate. Bed
      side PDA closure is a safe surgical procedure in both mature and premature
      babies. Here we aim to retrospectively present our 26 cases which were less than
      28 weeks and 1000 grams that underwent bed-side PDA ligation. METHODS: This
      retrospective study included 26 VLBWPN with PDA that underwent bed-side ligation
      between 2012 and 2015. Babies were born before the 28th gestational week (23-27
      weeks) and less than 1000 grams (489-970 gr). Of the 26, 15 were female and 11
      were male. Indomethacin was administered to all of the cases as the medical
      closing agent. The medication was stopped due to unwanted effects in 6 cases. All
      of the patients took medical treatment before surgery. RESULTS: No surgical
      mortality occurred during our study. One case of pneumothorax was recorded as
      late surgical complication. Five of the 26 patients were lost, and the most
      common cause of mortality was sepsis (in 3 cases). The remaining 21 cases were
      discharged on days 86-238. The follow-up periods of the patients were 2 moths - 3
      years. The most frequent problems encountered after discharge was chronic lung
      problems. CONCLUSIONS: Bed side PDA ligation surgery in the ICU is a safe method
      for VLBWPN with clinically significant PDA.

PMID- 27716330
TI  - Survival rate and perioperative data of patients who have undergone
      hemipelvectomy: a retrospective case series.
AB  - BACKGROUND: Hemipelvectomy is a major orthopedic surgical procedure indicated in
      specific situations. Although many studies discuss surgical techniques for
      hemipelvectomy, few studies have presented survival data, especially in
      underdeveloped countries. Additionally, there is limited information on
      anesthesia for orthopedic oncologic surgeries. The primary aim of this study was
      to determine the survival rate after hemipelvectomy, and the secondary aims were
      to evaluate anesthesia and perioperative care associated with hemipelvectomy and
      determine the influence of the surgical technique (external hemipelvectomy
      [amputation] or internal hemipelvectomy [limb sparing surgery]) on anesthesia and
      perioperative care in Brazil. METHODS: This retrospective case series collected
      data from 35 adult patients who underwent hemipelvectomy between 2000 and 2013.
      Survival rates after surgery were determined, and group comparisons were
      performed using the Kaplan-Meier method and the log-rank test. Mantel-Cox test
      and multiple linear regression analysis with stepwise forward selection were
      performed for univariate and multivariate analyses, respectively. RESULTS: Mean
      survival time was 32.8 +/- 4.6 months and 5-year survival rate was 27 %. Of the
      35 patients, 23 patients (65.7 %) underwent external hemipelvectomy and 12
      patients (34.3 %) underwent internal hemipelvectomy. The survival rate was
      significantly higher in patients with bone tumors than in those with soft tissue
      sarcomas (P = 0.024). The 5-year cumulative probability of survival was
      significantly lower in patients who underwent external hemipelvectomy than in
      those who underwent internal hemipelvectomy (P = 0.043). In the univariate and
      multivariate analyses, only advanced disease stage (3 and 4) was identified as a
      significant independent predictor of reduced survival (P = 0.0003). Balanced
      general anesthesia combined with epidural block was the most frequent anesthesia
      technique. Median intraoperative crystalloid volume and red blood cell
      transfusions were 3500 mL and 2 units, respectively. CONCLUSIONS: Overall mean
      survival time after hemipelvectomy was 32.8 months. Advanced disease stage might
      be independently associated with reduced survival. Smaller amounts of fluids and
      transfusions were administered and time to discharge was shorter. Acute and
      chronic pain as well as wound complications are still important challenges in
      hemipelvectomy.

PMID- 27716332
TI  - Anti-citrullinated protein antibodies and high levels of rheumatoid factor are
      associated with systemic bone loss in patients with early untreated rheumatoid
      arthritis.
AB  - BACKGROUND: Autoantibodies such as anti-citrullinated protein antibodies (ACPA)
      are major risk factors for articular bone destruction from the earliest phases of
      rheumatoid arthritis (RA). The aim of the current study was to determine whether
      RA-associated autoantibodies also impact on systemic bone loss in patients with
      early disease. METHODS: Systemic bone mineral density (BMD) was measured in the
      lumbar spine and the hip in 155 consecutive treatment-naive patients with early
      RA (median symptom duration 13 weeks). Demographic and disease-specific
      parameters, including clinical disease activity, ultrasonographic (US)
      examination of the hands and wrists, radiographic scoring of joint damage, ACPA
      and rheumatoid factor (RF) levels were recorded from all patients. Reduced BMD
      was defined as Z score <= -1 SD and analysed in relation to disease-related
      characteristics and autoantibody subgroups. RESULTS: Reduced BMD was found in
      25.5 % of the patients in the spine and 19.4 % in the hip. Symptom duration,
      clinical and US disease activity, functional disability and radiographic damage
      did not significantly impact on spine and hip BMD loss in regression analyses
      adjusted for possible confounders (age, gender, menopausal status, current
      smoking, body mass index). In contrast, ACPA positivity (at any level) negatively
      affected the spine Z-score (adjusted OR (95 % CI) 2.76 (1.19 to 6.42)); the hip Z
      score was affected by high titres only (adjusted OR (95 % CI) 2.96 (1.15 to
      7.66)). The association of ACPA with reduced BMD in the spine was confirmed even
      at low levels of RF (adjusted OR (95 % CI) 2.65 (1.01 to 7.24)), but was further
      increased by concomitant high RF (adjusted OR (95 % CI) 3.38 (1.11 to 10.34)). In
      contrast, Z scores in the hip were significantly reduced only in association with
      high ACPA and RF (adjusted OR (95 % CI) 4.96 (1.48 to 16.64)). CONCLUSIONS:
      Systemic BMD in patients with early RA is reduced in relation with ACPA
      positivity and high RF levels. This finding supports the notion that RA
      associated autoimmunity may have a direct causative role in bone remodeling.

PMID- 27716333
TI  - Catabolic and proinflammatory effects of leptin in chondrocytes are regulated by
      suppressor of cytokine signaling-3.
AB  - BACKGROUND: Previous studies provide evidence that adipokine leptin increases
      production of catabolic and proinflammatory factors in chondrocytes and serves as
      a link between obesity and osteoarthritis (OA). However, the magnitude of the
      response to leptin treatment varies greatly between chondrocytes from different
      donor patients. In the present study, we investigated the regulatory role of
      suppressor of cytokine signaling-3 (SOCS-3) in the leptin-induced responses in OA
      cartilage. METHODS: Cartilage and synovial fluid samples from 97 patients with OA
      undergoing knee replacement surgery were collected. Cartilage samples were
      cultured with leptin (10 MUg/ml), and the levels of proinflammatory and catabolic
      factors in synovial fluid and in the cartilage culture media, and SOCS-3
      expression in the cartilage were measured. The role of SOCS-3 in leptin signaling
      was further studied in H4 murine chondrocytes by downregulating SOCS-3 with
      siRNA. RESULTS: Leptin-induced expression of matrix metalloproteinases MMP-1, MMP
      3, MMP-13, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) were higher in the cartilage samples with low SOCS-3
      expression. Accordingly, downregulation of SOCS-3 by siRNA in H4 chondrocytes led
      to enhanced leptin-induced expression of MMP-3, MMP-13, IL-6 and iNOS. Synovial
      fluid leptin was associated positively, and cartilage SOCS-3 negatively with
      synovial fluid levels of MMPs in a multivariate model in obese (body mass index
      (BMI) >30 kg/m2) but not in non-obese (BMI <30 kg/m2) patients. CONCLUSIONS: Our
      results show, for the first time, that SOCS-3 regulates leptin-induced responses
      in cartilage, and could thus be a future drug target in the treatment or
      prevention of OA, especially in obese patients.

PMID- 27716335
TI  - Feasibility of community level interventions for pre-eclampsia: perspectives,
      knowledge and task-sharing from Nigeria, Mozambique, Pakistan and India.
AB  - Hypertensive disorders of pregnancy (HDP), particularly pre-eclampsia and
      eclampsia, remain one of the leading causes of maternal mortality and are
      contributory in many foetal/newborn deaths. This editorial discusses a supplement
      of seven papers which provide the results of the first round of the CLIP
      (Community Level Interventions for Pre-eclampsia) Feasibility Studies. These
      studies report a number of enablers and barriers in each setting, which have
      informed the implementation of a cluster-randomized trial (cRCT) aimed at
      reducing pre-eclampsia-related, and all-cause, maternal and perinatal mortality
      and major morbidity using community-based identification and treatment of pre
      eclampsia in selected geographies of Nigeria, Mozambique, Pakistan and India.
      This supplement unpacks the diverse community perspectives on determinants of
      maternal health, variant health worker knowledge and routine management of HDP,
      and viability of task sharing for preeclampsia identification and management in
      select settings. These studies demonstrate the need for strategies to improve
      health worker knowledge and routine management of HDP and consideration of
      expanding the role of community health workers to reach the most remote women and
      families with health education and access to health services.

PMID- 27716336
TI  - Adaptive vs. non-adaptive cognitive training by means of a personalized App: a
      randomized trial in people with multiple sclerosis.
AB  - BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS), but the
      definition of the best cognitive rehabilitation tools and features is still an
      open issue among researchers. The aims of the present study were to evaluate the
      effectiveness of COGNI-TRAcK (a customized application software delivering
      personalized working memory-based exercises) on cognitively impaired people with
      MS and to investigate the effects of an adaptive vs. a non-adaptive cognitive
      training administered by means of COGNI-TRAcK. METHODS: Twenty eight patients (20
      women, age 47.5 +/- 9.3 years, Expanded Disability Status Scale score 3.8 +/-
      1.9) were randomized in two homogeneous groups, both performing a 8-week home
      based cognitive rehabilitation treatment by means of COGNI-TRAcK. The study group
      (ADAPT-gr) underwent an adaptive training given by the automatic adjustment of
      tasks difficulty to the subjects' performance, whilst the control group (CONST
      gr) was trained at constant difficulty levels. Before and after the treatment,
      patients' cognitive status was assessed using a gold standard neuropsychological
      evaluation. Moreover, the mostly affected cognitive domains in MS (i.e.,
      attention, concentration and information processing speed) were also assessed 6
      months after the end of the treatment. RESULTS: The analysis of variance showed a
      significant Group*Time interaction in six out of ten tests of the cognitive
      evaluation. Post-hoc analysis revealed a significant improvement between the
      performances before and after the intervention only in the ADAPT-gr in tests
      evaluating verbal memory acquisition (p <0.05) and delayed recall (p = 0.001),
      verbal fluency (p = 0.01), sustained attention, concentration and information
      processing speed (p < 0.01). This last effect was maintained also after 6 months
      (p < 0.05). CONCLUSIONS: We concluded that COGNI-TRAcK represents a suitable tool
      to administer a personalized training to cognitively impaired subjects and that
      an adaptive working load is a crucial feature determining the effectiveness of
      cognitive treatment, allowing transfer effects to several cognitive domains and
      long-term maintenance of results.

PMID- 27716337
TI  - Clinical and paraclinical profile, and predictors of outcome in 90 cases of scrub
      typhus, Meghalaya, India.
AB  - BACKGROUND: India is an integral component of "tsutsugamushi triangle" which
      depicts a part of the globe endemic to scrub typhus. Owing to frequent outbreaks
      witnessed in different parts of the country in the recent past, scrub typhus is
      described as a re-emerging infectious disease in India. The present study aimed
      to study the clinical and paraclinical profile, complications and predictors of
      outcome among 90 cases of scrub typhus diagnosed in a hospital of north-eastern
      India from Sept 2011 to Aug 2012. METHODS: A longitudinal study was conducted in
      a hospital of Meghalaya, India between Sept 2011 and Aug 2012. Diagnosis of scrub
      typhus was arrived by SD BIOLINE tsutsugamushi (solid phase immunochromatographic
      assay) rapid diagnostic test for antibodies (IgM, IgG or IgA). Descriptive
      analyses of age, gender, geographic area, symptoms and signs, treatment,
      laboratory findings, complications, and outcome were conducted. Relative risk
      (RR) with 95 % confidence interval (CI) was computed for Multiple Organ
      Dysfunction Syndrome (MODS) and mortality. Binary logistic regression was applied
      to the significant correlates (P < 0.05) on univariate analysis to identify the
      predictors of MODS and mortality in scrub typhus. RESULTS: As many as 662
      clinically suspected scrub typhus patients were tested and 90 (13.6 %) were
      diagnosed to have scrub typhus. Out of 90 patients, 52.2 % (n = 47) were males
      and their mean (SD) age was 36.29 (13.38) years. Fever of <7 days (n = 75, 83.3
      %), myalgia (n = 56, 62.2 %), pain abdomen (n = 24, 26.7 %), headache (n = 24,
      26.7 %), nausea/vomiting (n = 21, 23.3 %), dry cough (n = 21, 23.3 %),
      hepatomegaly (n = 24, 26.7 %), splenomegaly (n = 22, 24.4 %), and lymphadenopathy
      (n = 20, 22.2 %) were the predominant clinical features. Eschar was seen in 10
      patients (11.1 %). One third (n = 30) of the patients developed at least one
      systemic complication. Acute hepatitis (n = 15, 16.7 %), pneumonitis (n = 14,
      15.6 %), and acute kidney injury (n = 11, 12.2 %) were the common complications.
      MODS was seen in 14.4 % (n = 13) and 38.5 % (n = 5) of the patients with MODS
      died. Overall, case fatality rate was 5.15 % (n = 5). On univariate analysis,
      platelets <100 000/mm3, serum creatinine >1.5 mg/dl, and transaminase (AST, ALT
      or both) >500 U/L were associated with MODS (P < 0.001) and mortality (P < 0.05).
      In addition, serum bilirubin >3 mg/dl was also associated with MODS (P < 0.001).
      On applying binary logistic regression, serum creatinine >1.5 mg/dl was a
      predictor of MODS (OR: 76.1, 95 % CI: 4.9-1175.6) and mortality (OR: 18.03, 95 %
      CI: 1.38-235.1). CONCLUSION: In this study setting, approximately one-seventh
      (13.6 %) of the acute undifferentiated febrile illness were due to scrub typhus.
      Systemic complications were common (33.3 %). Serum creatinine >1.5 mg/dl was a
      predictor of MODS and mortality.

PMID- 27716334
TI  - Multiple organ dysfunction and systemic inflammation after spinal cord injury: a
      complex relationship.
AB  - Spinal cord injury (SCI) is a devastating event that results in significant
      physical disabilities for affected individuals. Apart from local injury within
      the spinal cord, SCI patients develop a variety of complications characterized by
      multiple organ dysfunction or failure. These disorders, such as neurogenic pain,
      depression, lung injury, cardiovascular disease, liver damage, kidney
      dysfunction, urinary tract infection, and increased susceptibility to pathogen
      infection, are common in injured patients, hinder functional recovery, and can
      even be life threatening. Multiple lines of evidence point to pathological
      connections emanating from the injured spinal cord, post-injury systemic
      inflammation, and immune suppression as important multifactorial mechanisms
      underlying post-SCI complications. SCI triggers systemic inflammatory responses
      marked by increased circulation of immune cells and pro-inflammatory mediators,
      which result in the infiltration of inflammatory cells into secondary organs and
      persistence of an inflammatory microenvironment that contributes to organ
      dysfunction. SCI also induces immune deficiency through immune organ dysfunction,
      resulting in impaired responsiveness to pathogen infection. In this review, we
      summarize current evidence demonstrating the relevance of inflammatory conditions
      and immune suppression in several complications frequently seen following SCI. In
      addition, we highlight the potential pathways by which inflammatory and immune
      cues contribute to multiple organ failure and dysfunction and discuss current
      anti-inflammatory approaches used to alleviate post-SCI complications. A
      comprehensive review of this literature may provide new insights into therapeutic
      strategies against complications after SCI by targeting systemic inflammation.

PMID- 27716338
TI  - Rational design of cancer gene panels with OncoPaD.
AB  - BACKGROUND: Profiling the somatic mutations of genes which may inform about tumor
      evolution, prognostics and treatment is becoming a standard tool in clinical
      oncology. Commercially available cancer gene panels rely on manually gathered
      cancer-related genes, in a "one-size-fits-many" solution. The design of new
      panels requires laborious search of literature and cancer genomics resources,
      with their performance on cohorts of patients difficult to estimate. RESULTS: We
      present OncoPaD, to our knowledge the first tool aimed at the rational design of
      cancer gene panels. OncoPaD estimates the cost-effectiveness of the designed
      panel on a cohort of tumors and provides reports on the importance of individual
      mutations for tumorigenesis or therapy. With a friendly interface and intuitive
      input, OncoPaD suggests researchers relevant sets of genes to be included in the
      panel, because prior knowledge or analyses indicate that their mutations either
      drive tumorigenesis or function as biomarkers of drug response. OncoPaD also
      provides reports on the importance of individual mutations for tumorigenesis or
      therapy that support the interpretation of the results obtained with the designed
      panel. We demonstrate in silico that OncoPaD designed panels are more cost
      effective-i.e. detect a maximum fraction of tumors in the cohort by sequencing a
      minimum quantity of DNA-than available panels. CONCLUSIONS: With its unique
      features, OncoPaD will help clinicians and researchers design tailored next
      generating sequencing (NGS) panels to detect circulating tumor DNA or biopsy
      specimens, thereby facilitating early and accurate detection of tumors, genomics
      informed therapeutic decisions, patient follow-up and timely identification of
      resistance mechanisms to targeted agents. OncoPaD may be accessed through
      http://www.intogen.org/oncopad.

PMID- 27716340
TI  - Pharmacokinetics of calycopterin and xanthmicrol, two polymethoxylated
      hydroxyflavones with anti-angiogenic activities from Dracocephalum kotschyi
      Bioss.
AB  - BACKGROUND: Recently flavonoids have attracted the attention of researchers in
      the fight against cancer. Calycopterin and xanthomicrol, are two polymethoxylated
      flavonoids found in the aerial parts of Dracocephalum kotschyi Bioss.. We have
      recently shown that these compounds possess antiangiogenic activity and may be of
      value as potential anticancer agents. In order to demonstrate putative in vivo
      antitumor effect of these compounds we needed preliminary information on both
      pharmacokinetics and toxicological properties of these two agents. METHOD: A new
      online SPE HPLC method for measurement of calycopterin and xanthomicrol in rat
      plasma was developed. Pharmacokinetic parameters of calycopterin and
      xanthomicrol, after i.v. administration in rats, were determined. RESULTS: The
      plasma half-life for both agents was around 4 h, however, the volume of
      distribution of calycopterin appeared to be about 8 times greater than
      xanthomicrol. This was probably due the greater hydrophobicity of the former
      which had other consequences such as much smaller maximum plasma concentration of
      calycopterin compared to its less methoxylated congener. Preliminary
      toxicological study of xanthomicrol failed to show any behavioral, histological
      and biochemical adverse effects after repeated administrations of high doses.
      Pharmacokinetics of xanthomicrol in rats.

PMID- 27716339
TI  - Improving Ghana's mental healthcare through task-shifting- psychiatrists and
      health policy directors perceptions about government's commitment and the role of
      community mental health workers.
AB  - BACKGROUND: The scarcity of mental health professionals places specialist
      psychiatric care out of the reach of most people in low and middle income
      countries. There is growing interest in the effectiveness of task shifting as a
      strategy for targeting expanding health care demands in settings with shortages
      of qualified health personnel. Given this background, the aim of our study was to
      examine the perceptions of psychiatrists and health policy directors about the
      policy to expand mental health care delivery in Ghana through a system of task
      shifting from psychiatrists to community mental health workers (CMHWs). METHODS:
      A self-administered semi-structured questionnaire was developed and administered
      to 11 psychiatrists and 29 health policy directors. Key informant interviews were
      also held with five psychiatrists and four health policy directors. Quantitative
      data were analysed using descriptive statistics. Qualitative data were analysed
      thematically. RESULTS: Almost all the psychiatrists and 23 (79.3 %) health policy
      directors were aware of the policy of the Government of Ghana to improve on the
      human resource base within mental health through a system of task-shifting.
      Overall, about half of the psychiatrists and 9 (31 %) health policy directors
      perceived there is some professional resistance to the implementation of the
      policy of task shifting. The majority of respondents were of the view that CMHWs
      should be allowed to assess, diagnose and treat most of the common mental
      disorders. The respondents identified that CMHWs usually perform two sets of
      roles, namely; officially assigned roles for which they have the requisite
      training and assumed roles for which they usually do not have the requisite
      training. The stakeholders identified multiple challenges associated with current
      task shifting arrangements within Ghana's mental health delivery system,
      including inadequate training and supervision, poor awareness of the scope of
      their expertise on the part of the CMHWs. CONCLUSION: Psychiatrists and health
      policy directors support the policy to expand mental health service coverage in
      Ghana through a system of task-shifting, despite their awareness of resistance
      from some professionals. It is important that the Government of Ghana upholds its
      commitment of expanding mental healthcare by maintaining and prioritizing its
      policy on task shifting and also providing the necessary resources to ensure its
      success.

PMID- 27716341
TI  - Celastrus orbiculatus extract inhibits the migration and invasion of human
      glioblastoma cells in vitro.
AB  - BACKGROUND: Gliomas are highly aggressive tumors of the nervous system, and
      current treatments fail to improve patient survival. To identify substances that
      can be used as treatments for gliomas, we examined the effect of Celastrus
      orbiculatus extract (COE) on the invasion and migration of human glioblastoma U87
      and U251 cells in vitro. METHODS: The effects of COE on cell viability and
      adhesion were tested using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H
      tetrazolium bromide assay and cell adhesion assay, respectively. The effects of
      COE on cell migration and invasion were assessed by a wound-healing assay and
      transwell migration and invasion assays. The effects of COE on the expression of
      epithelial-mesenchymal transition (EMT)-related proteins and matrix
      metalloproteinases (MMPs) were evaluated using western blot and gelatin
      zymography, respectively. Finally, the effect of COE on actin assembly was
      observed using phalloidin-tetramethylrhodamine isothiocyanate labeling and
      confocal laser scanning microscopy. RESULTS: We found that COE inhibited the
      adhesion, migration, and invasion of U87 and U251 cells in a dose-dependent
      manner. COE reduced N-cadherin and vimentin expression, increased E-cadherin
      expression, and reduced MMP-2 and MMP-9 expression in U87 and U251 cells.
      Furthermore, COE inhibited actin assembly in U87 and U251 cells. CONCLUSIONS: COE
      attenuates EMT, MMP expression, and actin assembly in human glioblastoma cells,
      thereby inhibiting their adhesion, migration, and invasion in vitro.

PMID- 27716342
TI  - Assessment of malaria control consultation and service posts in Yunnan, P. R.
      China.
AB  - BACKGROUND: This paper seeks to assess the function of malaria control
      consultation and service posts (MCCSPs) that are located on the border areas of
      Yunnan province, P.R. China, as a strategy for eliminating malaria among the
      mobile and migrant population in these areas. METHODS: A retrospective
      descriptive analytical study was conducted. Blood smear examinations conducted at
      all MCCSPs in Yunnan from 2008 to 2014 were analysed. A cross-sectional survey
      was conducted in 2014 to understand how the MCCSPs function and to elucidate the
      quality of the blood smear examinations that they conduct. RESULTS: Out of the
      surveyed MCCSPs, 66 % (39/59), 22 % (13/59), and 12 % (7/59) were attached to
      local township hospitals, village health clinics, and the county centre for
      disease control and prevention or private clinics, respectively. More than 64 %
      (38/59) of the posts' staff were part-time workers from township hospitals and
      village health facilities. Less than 31 % (18/59) of the posts' staff were full
      time workers. A total of 35 positive malaria cases were reported from seven
      MCCSPs in 2014. Four MCCSPs were unable to perform their functions due to under
      staffing in 2014. There was a small fluctuation in blood smear examinations from
      January 2008 to June 2009, with two peaks during the period from July 2009 to
      October 2010. The number of blood smear examinations has been increasing since
      2011. The yearly mean number of blood smear examinations in each post increased
      from 44 per month in 2011 to 109 per month in 2014, and the number of positive
      malaria cases detected by blood smear examinations has declined (chi 2 = 90.67, P
      = 0.000). The percentage of people from Yingjiang county getting blood smear
      examinations increased between 2008 and 2014, while percentages of the mobile
      population including Myanmar people, people from other provinces, and people from
      other Yunnan counties getting blood smear examinations decreased. CONCLUSION:
      MCCSPs face challenges in the phase of malaria elimination in Yunnan, China. New
      case detection strategies should be designed for MCCSPs taking into account the
      current trends of migration.

PMID- 27716343
TI  - High levels of biomarkers of collagen remodeling are associated with increased
      mortality in COPD - results from the ECLIPSE study.
AB  - BACKGROUND: There is a need to identify individuals with COPD at risk for disease
      progression and mortality. Lung tissue remodeling is associated with the release
      of extracellular matrix (ECM) fragments into the peripheral circulation. We
      hypothesized that ECM remodeling was associated with mortality in COPD and
      measured neo-epitopes originating from ECM proteins associated with lung tissue
      remodeling. METHODS: Biomarkers of ECM remodeling were assessed in a
      subpopulation (n = 1000) of the Evaluation of COPD Longitudinally to Identify
      Predictive Surrogate End-points (ECLIPSE) cohort. Validated immunoassays
      measuring serological neo-epitopes produced by proteolytic cleavage associated
      with degradation of collagen type I, III, IV, and VI, elastin, and biglycan, and
      formation of collagen type VI as well as fibrinogen and C-reactive protein were
      used. Multivariate models were used to assess the prognostic value of these
      biomarkers. RESULTS: Thirty subjects (3.0 %) died during follow-up. Non-survivors
      were older, had reduced exercise capacity, increased dyspnea score, and included
      fewer current smokers. All collagen biomarkers were significantly elevated in non
      survivors compared to survivors. Mortality risk was significantly increased for
      subjects with collagen remodeling biomarkers in the upper quartile, especially
      for the degradation fragment of collagen type IV C6M (hazard ratio 6.6 [95 %
      confidence interval 2.9-15.2], P < 0.0001) after adjusting for relevant
      confounders. CONCLUSIONS: Serological biomarkers of collagen remodeling were
      strongly associated with mortality in subjects with COPD indicating that
      assessment of tissue turnover in the parenchyma and small airways may be useful
      in the prognosis of COPD. TRIAL REGISTRATION: NCT00292552 , GSK Study No.
      SCO104960.

PMID- 27716344
TI  - Comparison of different cardiovascular magnetic resonance sequences for native
      myocardial T1 mapping at 3T.
AB  - BACKGROUND: T1 mapping based on cardiovascular magnetic resonance (CMR) is a
      novel approach using the magnetic relaxation T1 time as a quantitative marker for
      myocardial tissue composition. Various T1 mapping sequences are being used, with
      different strengths and weaknesses. Data comparing different sequences head to
      head however are sparse. METHODS: We compared three T1 mapping sequences,
      ShMOLLI, MOLLI and SASHA in phantoms and in a mid-ventricular slice of 40 healthy
      individuals (mean age 59 +/- 7 years, 45 % male) with low (68 %) or moderate
      cardiovascular risk. We calculated global and segmental T1 in vivo through
      exponential curve fitting and subsequent parametric mapping. We also analyzed
      image quality and inter-observer reproducibility. RESULTS: There was no
      association of T1 with cardiovascular risk groups. T1 however differed
      significantly depending on the sequence, with SASHA providing consistently higher
      mean values than ShMOLLI and MOLLI (1487 +/- 36 ms vs. 1174 +/- 37 ms and 1199 +/
      28 ms, respectively; p < 0.001). This difference between sequences was much
      smaller in phantom measurements. In patients, segmental values were lower in the
      anterior wall for all sequences. Image quality, in general good for the steady
      state-free-precession readouts in all sequences, was lower for SASHA parametric
      maps. On multivariate regression analysis, a longer T1 measured by MOLLI was
      correlated with lower ejection fraction and female gender. Inter-observer
      variability as assessed by intra-class correlation coefficients was excellent for
      all sequences (ShMOLLI: 0.995; MOLLI: 0.991; SASHA: 0.961; all p < 0.001).
      CONCLUSION: In a cross-sectional population with low to moderate cardiovascular
      risk, we observed a variation in T1 mapping results between inversion-recovery
      vs. saturation-recovery sequences in vivo, which were less evident in phantom
      images, despite a small interobserver variability. Thus, physiological factors,
      most likely related to B1 inhomogeneities, and tissue-specific properties, like
      magnetization transfer, that impact T1 values in vivo, render phantom validation
      insufficient, and have to be further investigated for a better understanding of
      the clinical utility of different T1 mapping approaches. TRIAL REGISTRATION:
      "Canadian Alliance For Healthy Hearts and Minds" - ClinicalTrials.gov NCT02220582
      ; registered August 18, 2014.

PMID- 27716345
TI  - Dissection of exopolysaccharide biosynthesis in Kozakia baliensis.
AB  - BACKGROUND: Acetic acid bacteria (AAB) are well known producers of commercially
      used exopolysaccharides, such as cellulose and levan. Kozakia (K.) baliensis is a
      relatively new member of AAB, which produces ultra-high molecular weight levan
      from sucrose. Throughout cultivation of two K. baliensis strains (DSM 14400, NBRC
      16680) on sucrose-deficient media, we found that both strains still produce high
      amounts of mucous, water-soluble substances from mannitol and glycerol as (main)
      carbon sources. This indicated that both Kozakia strains additionally produce new
      classes of so far not characterized EPS. RESULTS: By whole genome sequencing of
      both strains, circularized genomes could be established and typical EPS forming
      clusters were identified. As expected, complete ORFs coding for levansucrases
      could be detected in both Kozakia strains. In K. baliensis DSM 14400 plasmid
      encoded cellulose synthase genes and fragments of truncated levansucrase operons
      could be assigned in contrast to K. baliensis NBRC 16680. Additionally, both K.
      baliensis strains harbor identical gum-like clusters, which are related to the
      well characterized gum cluster coding for xanthan synthesis in Xanthomanas
      campestris and show highest similarity with gum-like heteropolysaccharide (HePS)
      clusters from other acetic acid bacteria such as Gluconacetobacter diazotrophicus
      and Komagataeibacter xylinus. A mutant strain of K. baliensis NBRC 16680 lacking
      EPS production on sucrose-deficient media exhibited a transposon insertion in
      front of the gumD gene of its gum-like cluster in contrast to the wildtype
      strain, which indicated the essential role of gumD and of the associated gum
      genes for production of these new EPS. The EPS secreted by K. baliensis are
      composed of glucose, galactose and mannose, respectively, which is in agreement
      with the predicted sugar monomer composition derived from in silico genome
      analysis of the respective gum-like clusters. CONCLUSIONS: By comparative sugar
      monomer and genome analysis, the polymeric substances secreted by K. baliensis
      can be considered as unique HePS. Via genome sequencing of K. baliensis DSM 14400
      + NBRC 16680 we got first insights into the biosynthesis of these novel HePS,
      which is related to xanthan and acetan biosynthesis. Consequently, the present
      study provides the basis for establishment of K. baliensis strains as novel
      microbial cell factories for biotechnologically relevant, unique polysaccharides.

PMID- 27716347
TI  - Assessing the external validity of algorithms to estimate EQ-5D-3L from the
      WOMAC.
AB  - BACKGROUND: The use of mapping algorithms have been suggested as a solution to
      predict health utilities when no preference-based measure is included in the
      study. However, validity and predictive performance of these algorithms are
      highly variable and hence assessing the accuracy and validity of algorithms
      before use them in a new setting is of importance. The aim of the current study
      was to assess the predictive accuracy of three mapping algorithms to estimate the
      EQ-5D-3L from the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) among Swedish people with knee disorders. Two of these algorithms
      developed using ordinary least squares (OLS) models and one developed using
      mixture model. METHODS: The data from 1078 subjects mean (SD) age 69.4 (7.2)
      years with frequent knee pain and/or knee osteoarthritis from the Malmo
      Osteoarthritis study in Sweden were used. The algorithms' performance was
      assessed using mean error, mean absolute error, and root mean squared error. Two
      types of prediction were estimated for mixture model: weighted average (WA), and
      conditional on estimated component (CEC). RESULTS: The overall mean was
      overpredicted by an OLS model and underpredicted by two other algorithms (P <
      0.001). All predictions but the CEC predictions of mixture model had a narrower
      range than the observed scores (22 to 90 %). All algorithms suffered from
      overprediction for severe health states and underprediction for mild health
      states with lesser extent for mixture model. While the mixture model outperformed
      OLS models at the extremes of the EQ-5D-3D distribution, it underperformed around
      the center of the distribution. CONCLUSIONS: While algorithm based on mixture
      model reflected the distribution of EQ-5D-3L data more accurately compared with
      OLS models, all algorithms suffered from systematic bias. This calls for caution
      in applying these mapping algorithms in a new setting particularly in samples
      with milder knee problems than original sample. Assessing the impact of the
      choice of these algorithms on cost-effectiveness studies through sensitivity
      analysis is recommended.

PMID- 27716346
TI  - Fundamentals of aerosol therapy in critical care.
AB  - Drug dosing in critically ill patients is challenging due to the altered drug
      pharmacokinetics-pharmacodynamics associated with systemic therapies. For many
      drug therapies, there is potential to use the respiratory system as an
      alternative route for drug delivery. Aerosol drug delivery can provide many
      advantages over conventional therapy. Given that respiratory diseases are the
      commonest causes of critical illness, use of aerosol therapy to provide high
      local drug concentrations with minimal systemic side effects makes this route an
      attractive option. To date, limited evidence has restricted its wider
      application. The efficacy of aerosol drug therapy depends on drug-related factors
      (particle size, molecular weight), device factors, patient-related factors
      (airway anatomy, inhalation patterns) and mechanical ventilation-related factors
      (humidification, airway). This review identifies the relevant factors which
      require attention for optimization of aerosol drug delivery that can achieve
      better drug concentrations at the target sites and potentially improve clinical
      outcomes.

PMID- 27716348
TI  - Whole-body patterns of the range of joint motion in young adults: masculine type
      and feminine type.
AB  - BACKGROUND: Understanding the whole-body patterns of joint flexibility and their
      related biological and physical factors contributes not only to clinical
      assessments but also to the fields of human factors and ergonomics. In this
      study, ranges of motion (ROMs) at limb and trunk joints of young adults were
      analysed to understand covariation patterns of different joint motions and to
      identify factors associated with the variation in ROM. METHODS: Seventy-eight
      healthy volunteers (42 males and 36 females) living on Okinawa Island, Japan,
      were recruited. Passive ROM was measured at multiple joints through the whole
      body (31 measurements) including the left and right side limbs and trunk.
      RESULTS: Comparisons between males and females, dominant and non-dominant sides,
      and antagonistic motions indicated that body structures influence ROMs. In
      principal component analysis (PCA) on the ROM data, the first principal component
      (PC1) represented the sex difference and a similar covariation pattern appeared
      in the analysis within each sex. Multiple regression analysis showed that this
      component was associated with sex, age, body fat %, iliospinale height, and leg
      extension strength. CONCLUSIONS: The present study identified that there is a
      spectrum of "masculine" and "feminine" types in the whole-body patterns of joint
      flexibility. This study also suggested that body proportion and composition,
      muscle mass and strength, and possibly skeletal structures partly explain such
      patterns. These results would be important to understand individual variation in
      susceptibility to joint injuries and diseases and in one's suitable and effective
      postures and motions.

PMID- 27716349
TI  - Reduced volume SIB-IMRT/IGRT to head and neck cancer in elderly and frail
      patients: outcome and toxicity.
AB  - BACKGROUND: Especially elderly and frail patients have a limited ability to
      compensate for side effects of a radical treatment of head and neck malignancies.
      Limiting the target volume to the macroscopic disease, without prophylactic nodal
      irradiation, might present a feasible approach for these patients. The present
      work therefore aims evaluating an IMRT/IGRT -SIB concept for safety and efficacy.
      METHODS: The study retrospectively enrolled 27 patients with head and neck
      cancers treated between 01/2012 and 05/2015. We evaluated patient files for
      clinical status, concomitant diseases, treatment side, and treatment volumes as
      well as for side effects and tumor responses. To describe efficacy and risk
      factors for worse outcome and higher grade toxicities, we performed cox
      regression analysis as well as Kaplan-Meier survival time analysis. RESULTS:
      Median survival was 181 days, 75 % patients showed an early local response at six
      weeks of follow up. Most patients developed mild to moderate acute toxicities,
      only one patient with grade IV mucositis was seen. The grade of toxicities was
      correlated to the size of the PTV. Concomitant diseases, metastatic disease, and
      G3 Grading were indicators for worse prognosis. CONCLUSION: The IMRT/IGRT SIB
      concept is a safe and feasible radiotherapy concept for patients not able or not
      willing to undergo radical treatment.

PMID- 27716350
TI  - Opportunities and obstacles to the development of nanopharmaceuticals for human
      use.
AB  - Pharmaceutical nanotechnology has generated breakthrough developments in
      improving health care and human life from its emergence. The biomaterials
      employed mainly aim at improving drug delivery systems, imaging and diagnostic
      technologies while the nanoscale materials are in widespread use in other
      industries such as electronics and optics. Such advancement may revolutionize the
      drug development and therapy with new and more efficient treatments. Although,
      nanotechnology assists humankind in improving its well being, it has certain
      limitations that entail thorough investigation by the regulatory and scientific
      authorities. To address concerns regarding the safety and toxicity profile of the
      nanopharmaceuticals, we have reviewed the challenges and solutions of
      nanopharmaceuticals use in human health and the related health risks. In this
      regard, regulatory and scientific bodies such as countries' Food and Drug
      Administration (FDA), Organization for Economic Co-operation and Development
      (OECD), European Medicine Agency (EMA), Environmental Protection Agency (EPA),
      National Institute for Occupational Safety and Health (NIOSH), and World Health
      Organization (WHO) can participate in developing and reinforcing safety measures
      and regulatory frameworks to insure the public health. The regulatory authorities
      may enforce the nanopharmaceutical industries to conduct comprehensive toxicity
      tests and monitor the adverse drug reaction reports in close collaboration with
      the scientific community to act accordingly and inform the public as the
      implementation of the strategy. Nanopharmaceuticals have tremendous potential for
      human use as therapeutic or diagnostic agents. But their toxicity profile should
      be well addressed and the respective regulatory framework developed and
      reinforced by the authorities.

PMID- 27716351
TI  - Does the optimal position of the acetabular fragment should be within the
      radiological normal range for all developmental dysplasia of the hip? A patient
      specific finite element analysis.
AB  - BACKGROUND: The success of Bernese periacetabular osteotomy depends significantly
      on how extent the acetabular fragment can be corrected to its optimal position.
      This study was undertaken to investigate whether correcting the acetabular
      fragment into the so-called radiological "normal" range is the best choice for
      all developmental dysplasia of the hip with different severities of dysplasia
      from the biomechanical view? If not, is there any correlation between the
      biomechanically optimal position of the acetabular fragment and the severity of
      dysplasia? METHODS: Four finite element models with different severities of
      dysplasia were developed. The virtual periacetabular osteotomy was performed with
      the acetabular fragment rotated anterolaterally to incremental center-edge
      angles; then, the contact area and pressure and von Mises stress in the cartilage
      were calculated at different correction angles. RESULTS: The optimal position of
      the acetabular fragment for patients 1, 2, and 3 was when the acetabular fragment
      rotated 17 degrees  laterally (with the lateral center-edge angle of 36 degrees 
      and anterior center-edge angle of 58 degrees ; both were slightly larger than the
      "normal" range), 25 degrees  laterally following further 5 degrees  anterior
      rotation (with the lateral center-edge angle of 31 degrees  and anterior center
      edge angle of 51 degrees ; both were within the "normal" range), and 30 degrees 
      laterally following further 10 degrees  anterior rotation (with the lateral
      center-edge angle of 25 degrees  and anterior center-edge angle of 40 degrees ;
      both were less than the "normal" range), respectively. CONCLUSIONS: The optimal
      corrective position of the acetabular fragment is severity dependent rather than
      within the radiological "normal" range for developmental dysplasia of the hip. We
      prudently proposed that the optimal correction center-edge angle of mild,
      moderate, and severe developmental dysplasia of the hip is slightly larger than
      the "normal" range, within the "normal" range, and less than the lower limit of
      the "normal" range, respectively.

PMID- 27716352
TI  - Integrating one health in national health policies of developing countries:
      India's lost opportunities.
AB  - BACKGROUND: Globally, the threat of infectious diseases, particularly emerging
      infectious diseases, originating at the human-animal-environment interface, has
      caught health systems off guard. With forecasts that future pathogen emergence
      will be centred in hotspots in Asia, Africa, and Latin America, the need to
      prepare policy frameworks that can combat this threat is urgent. DISCUSSION:
      Emergence of diseases such as avian influenza and Ebola virus disease, which
      threatened social disruption, have established the need for intersectoral
      coordination/collaboration. These events led to the initiation of establishing
      institutionalised collaborative frameworks in India to adopt a One Health
      approach to disease prevention and control. However, the gains made in influenza
      control could not be adapted to other infectious diseases. Intersectoral
      coordination was briefly carried out, more as a reactive response to threats. The
      systemic failure to sustain such efforts have therefore, only undermined a
      coordinated response. The recent draft National Health Policy, 2015, has also
      failed to establish the need for intersectoral coordination in disease control
      approaches. Neglecting the need to endorse linkages between human health, animal
      health and husbandry, agriculture, and environmental sectors, has led to
      duplicative and weak response systems. The absence of health impact assessment
      with respect to the development agenda in policies, has cast negative effects on
      the health and wellbeing of man, animal, and the environment. Lack of attention
      to building core capacity in these critical sectors has further raised challenges
      in designing and deploying mitigation strategies. With developing countries like
      India being home to a major portion of the world's poorest livestock farmers, the
      absence of a policy discourse that endorses the One Health approach in
      development and health policies is a major hurdle in eliminating poverty and
      poverty-related diseases. CONCLUSIONS: The adoption of One Health approaches in
      health and related sectoral policies is a critical policy requirement for India
      and other developing countries. The goal should be to not just establish
      preparedness plans, but also to encourage a policy environment where assessment
      and mitigation of downstream impacts of different agenda are incorporated.

PMID- 27716354
TI  - Accuracy of p57KIP2 compared with genotyping for the diagnosis of complete
      hydatidiform mole: protocol for a systematic review and meta-analysis.
AB  - BACKGROUND: Distinguishing hydatidiform moles (HMs) from non-molar specimens and
      the subclassification of HM are important because complete hydatidiform mole
      (CHM) is associated with an increased risk of gestational trophoblastic
      neoplasia. However, diagnosis based solely on morphology has poor interobserver
      reproducibility. Recent studies have demonstrated that the use of p57KIP2
      immunostaining improves diagnostic accuracy for CHM. METHODS: We will conduct a
      systematic review of prospective and retrospective studies to evaluate the
      accuracy of p57KIP2 immunostaining compared with molecular genotyping for the
      diagnosis of CHM. A high-sensitivity search strategy will be employed in MEDLINE,
      EMBASE, LILACS, The Grey Literature Report, OpenGrey, OAIster, and Cochrane
      CENTRAL. Two reviewers will independently screen all identified references for
      eligibility and extract data. The methodological quality and bias of the included
      studies will be assessed according to the Quality Assessment of Diagnostic
      Accuracy Studies (QUADAS-2) tool, and the overall quality of evidence will be
      assessed using the Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) approach. If a meta-analysis is possible, pooled estimates of
      sensitivity, specificity, and positive and negative likelihood ratios will be
      calculated using bivariate random-effects models. Statistical heterogeneity will
      be evaluated with I 2 statistics and explored through sensitivity analysis.
      DISCUSSION: There is considerable overlap between the histological features of
      molar and non-molar pregnancies and between complete and partial HMs, which
      results in significant interobserver variability in the diagnosis of CHM and its
      mimics. Therefore, molecular techniques are used to correctly diagnosis and treat
      CHM. However, these molecular diagnostic methods are technically difficult to
      perform, relatively costly, and unavailable in most pathology laboratories.
      According to our results, p57KIP2 immunostaining appears to be a practical and
      accurate adjunct for the diagnosis of CHM and its mimics because this technique
      is relatively simple, reliable, cost-efficient, and rapid. This systematic review
      will help to determine whether p57KIP2 immunostaining is an adequate alternative
      diagnostic test for CHM. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024181.

PMID- 27716353
TI  - The risks of overlooking the diagnosis of secreting pituitary adenomas.
AB  - Secreting pituitary adenomas that cause acromegaly and Cushing's disease, as well
      as prolactinomas and thyrotroph adenomas, are uncommon, usually benign, slow
      growing tumours. The rarity of these conditions means that their diagnosis is not
      familiar to most non-specialist physicians. Consequently, pituitary adenomas may
      be overlooked and remain untreated, and affected individuals may develop serious
      comorbidities that reduce their quality of life and life expectancy. Because many
      signs and symptoms of pituitary adenomas overlap with those of other, more common
      disorders, general practitioners and non-endocrinology specialists need to be
      aware of the "red flags" suggestive of these conditions. A long duration of
      active disease in patients with secreting pituitary adenomas is associated with
      an increased risk of comorbidities and reduced quality of life. Appropriate
      treatment can lead to disease remission, and, although some symptoms may persist
      in some patients, treatment usually reduces the incidence and severity of
      comorbidities and improves quality of life. Therefore, correct, early diagnosis
      and characterization of a pituitary adenoma is crucial for patients, to trigger
      timely, appropriate treatment and to optimize outcome. This article provides an
      overview of the epidemiology of hormonal syndromes associated with pituitary
      adenomas, discusses the difficulties of and considerations for their diagnosis,
      and reviews the comorbidities that may develop, but can be prevented, by accurate
      diagnosis and appropriate treatment. We hope this review will help general
      practitioners and non-endocrinology specialists to suspect secreting pituitary
      adenomas and refer patients to an endocrinologist for confirmation of the
      diagnosis and treatment.

PMID- 27716355
TI  - Use of explicit ICD9-CM codes to identify adult severe sepsis: impacts on
      epidemiological estimates.
AB  - BACKGROUND: Severe sepsis is a challenge for healthcare systems, and
      epidemiological studies are essential to assess its burden and trends. However,
      there is no consensus on which coding strategy should be used to reliably
      identify severe sepsis. This study assesses the use of explicit codes to define
      severe sepsis and the impacts of this on the incidence and in-hospital mortality
      rates. METHODS: We examined episodes of severe sepsis in adults aged >=18 years
      registered in the 2006-2011 national hospital discharge database, identified in
      an exclusive manner by two ICD-9-CM coding strategies: (1) those assigned
      explicit ICD-9-CM codes (995.92, 785.52); and (2) those assigned combined ICD-9
      CM infection and organ dysfunction codes according to modified Martin criteria.
      The coding strategies were compared in terms of the populations they defined and
      their relative implementation. Trends were assessed using Joinpoint regression
      models and expressed as annual percentage change (APC). RESULTS: Of 222 846
      episodes of severe sepsis identified, 138 517 (62.2 %) were assigned explicit
      codes and 84 329 (37.8 %) combination codes; incidence rates were 60.6 and 36.9
      cases per 100 000 inhabitants, respectively. Despite similar demographic
      characteristics, cases identified by explicit codes involved fewer comorbidities,
      fewer registered pathogens, greater extent of organ dysfunction (two or more
      organs affected in 60 % versus 26 % of cases) and higher in-hospital mortality
      (54.5 % versus 29 %; risk ratio 1.86, 95 % CI 1.83, 1.88). Between 2006 and 2011,
      explicit codes were increasingly implemented. Standardised incidence rates in
      this cohort increased over time with an APC of 12.3 % (95 % CI 4.4, 20.8); in the
      combination code cohort, rates increased by 3.8 % (95 % CI 1.3, 6.3). A
      decreasing trend in mortality was observed in both cohorts though the APC was 
      8.1 % (95 % CI -10.4, -5.7) in the combination code cohort and -3.5 % (95 % CI 
      3.9, -3.2) in the explicit code cohort. CONCLUSIONS: Our findings suggest greater
      and increasing use of explicit codes for adult severe sepsis in Spain. This trend
      will have substantial impacts on epidemiological estimates, because these codes
      capture cases featuring greater organ dysfunction and in-hospital mortality.

PMID- 27716356
TI  - Exosomes derived from HCC cells induce sorafenib resistance in hepatocellular
      carcinoma both in vivo and in vitro.
AB  - BACKGROUND: Exosomes are carriers of intercellular information and regulate the
      tumor microenvironment. They play an important role in drug resistance by
      transporting RNA molecules and proteins. However, their effects on sorafenib
      resistance in hepatocellular carcinoma (HCC) are not completely understood.
      METHODS: Exosomes were isolated from two invasive hepatoma cell lines (MHCC-97 L
      and MHCC-97H), and their roles in regulating sorafenib resistance in liver cancer
      cells as well as the underlying molecular mechanisms were determined. The
      exosomes were analyzed by TEM (transmission electron microscopy), DLS (dynamic
      light scattering) and Western blotting. Cell viability, cell death and the
      effects of exosomes on the HGF/c-Met/Akt signaling pathway in cancer cells were
      analyzed by MTT assays, FACS analysis and Western blotting, respectively.
      Moreover, the effects of exosomes on sorafenib resistance in vivo were
      investigated using a subcutaneous transplantation tumor model in athymic nude
      mice. RESULTS: Exosomes derived from HCC cells were of the expected size and
      expressed the exosomal markers CD9 and CD63. They induced sorafenib resistance in
      vitro by activating the HGF/c-Met/Akt signaling pathway and inhibiting sorafenib
      induced apoptosis. They also induced sorafenib resistance in vivo by inhibiting
      sorafenib-induced apoptosis. Moreover, exosomes derived from highly invasive
      tumor cells had greater efficacy than that of exosomes derived from less invasive
      cells. CONCLUSIONS: These data reveal the important role of HCC cell-derived
      exosomes in the drug resistance of liver cancer cells and demonstrate the
      intrinsic interaction between exosomes and their targeted tumor cells. This study
      suggests a new strategy for improving the effectiveness of sorafenib in treating
      HCC.

PMID- 27716358
TI  - Erratum to: Extensive next-generation sequencing analysis in chronic lymphocytic
      leukemia at diagnosis: clinical and biological correlations.

PMID- 27716357
TI  - How best to structure interdisciplinary primary care teams: the study protocol
      for a systematic review with narrative framework synthesis.
AB  - BACKGROUND: Western publicly funded health care systems increasingly rely on
      interdisciplinary teams to support primary care delivery and management of
      chronic conditions. This knowledge synthesis focuses on what is known in the
      academic and grey literature about optimal structural characteristics of teams.
      Its goal is to assess which factors contribute to the effective functioning of
      interdisciplinary primary care teams and improved health system outcomes, with
      specific focus on (i) team structure contribution to team process, (ii) team
      process contribution to primary care goals, and (iii) team structure contribution
      to primary care goals. METHODS AND DESIGN: The systematic search of academic
      literature focuses on four chronic conditions and co-morbidities. Within this
      scope, qualitative and quantitative studies that assess the effects of team
      characteristics (funding, governance, organization) on care process and patient
      outcomes will be searched. Electronic databases (Ovid MEDLINE, Embase, CINAHL,
      PAIS, Web of Science) will be searched systematically. Online web-based searches
      will be supported by the Grey Matters Tool. Studies will be included, if they
      report on interdisciplinary primary care in publicly funded Western health
      systems, and address the relationships between team structure, process, and/or
      patient outcomes. Studies will be selected in a three-stage screening process
      (title/abstract/full text) by two independent reviewers in each stage. Study
      quality will be assessed using the Mixed Methods Assessment Tool. An a priori
      framework will be applied to data extraction, and a narrative framework approach
      is used for the synthesis. DISCUSSION: Using an integrated knowledge translation
      approach, an electronic decision support tool will be developed for decision
      makers. It will be searchable along two axes of inquiry: (i) what primary care
      goals are supported by specific team characteristics and (ii) how should teams be
      structured to support specific primary care goals? The results of this evidence
      review will contribute directly to the design of interdisciplinary primary care
      teams. The optimized design will support the goals of primary care, contributing
      to the improved health of populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42016041884.

PMID- 27716359
TI  - TrhOnt: building an ontology to assist rehabilitation processes.
AB  - BACKGROUND: One of the current research efforts in the area of biomedicine is the
      representation of knowledge in a structured way so that reasoning can be
      performed on it. More precisely, in the field of physiotherapy, information such
      as the physiotherapy record of a patient or treatment protocols for specific
      disorders must be adequately modeled, because they play a relevant role in the
      management of the evolutionary recovery process of a patient. In this scenario,
      we introduce TRHONT, an application ontology that can assist physiotherapists in
      the management of the patients' evolution via reasoning supported by semantic
      technology. METHODS: The ontology was developed following the NeOn Methodology.
      It integrates knowledge from ontological (e.g. FMA ontology) and non-ontological
      resources (e.g. a database of movements, exercises and treatment protocols) as
      well as additional physiotherapy-related knowledge. RESULTS: We demonstrate how
      the ontology fulfills the purpose of providing a reference model for the
      representation of the physiotherapy-related information that is needed for the
      whole physiotherapy treatment of patients, since they step for the first time
      into the physiotherapist's office, until they are discharged. More specifically,
      we present the results for each of the intended uses of the ontology listed in
      the document that specifies its requirements, and show how TRHONT can answer the
      competency questions defined within that document. Moreover, we detail the main
      steps of the process followed to build the TRHONT ontology in order to facilitate
      its reproducibility in a similar context. Finally, we show an evaluation of the
      ontology from different perspectives. CONCLUSIONS: TRHONT has achieved the
      purpose of allowing for a reasoning process that changes over time according to
      the patient's state and performance.

PMID- 27716360
TI  - Differences in joint morphology between the knee and ankle affect the repair of
      osteochondral defects in a rabbit model.
AB  - BACKGROUND: Although differences in the results of the bone marrow stimulation
      technique between the knee and ankle have been reported, a detailed mechanism for
      those differences has not been clarified. The purpose of this study was to
      examine whether morphological differences between the knee and ankle joint affect
      the results of drilling as treatment for osteochondral defects in a rabbit model.
      METHODS: Osteochondral defects were created at the knee and ankle joint in the
      rabbit. In the knee, osteochondral defects were created at the medial femoral
      condyle (MFC) and patellar groove (PG). At the ankle, defects were created in the
      talus at either a covered or uncovered area by the tibial plafond. After creating
      the osteochondral defect, drilling was performed. At 4, 8, and 12 weeks after
      surgery, repair of the osteochondral defects were evaluated histologically. The
      proliferation of rabbit chondrocytes and proteoglycan release of cartilage tissue
      in response to IL-1beta were analyzed in vitro in both joints. RESULTS: At 8
      weeks after surgery, hyaline cartilage repair was observed in defects at the
      covered area of the talus and the MFC. At 12 weeks, hyaline cartilage with a
      normal thickness was observed for the defect at the covered area of the talus,
      but not for the defect at the MFC. At 12 weeks, subchondral bone formation
      progressed and a normal contour of subchondral bone was observed on CT in the
      defect at the covered area of the talus. No significant differences in
      chondrocyte proliferation rate and proteoglycan release were detected between the
      knee and ankle in vitro. CONCLUSIONS: Our results demonstrate that the covered
      areas of the talus show early and sufficient osteochondral repair compared to
      that of the knee and the uncovered areas of the talus. These results suggest that
      the congruent joint shows better subchondral repair prior to cartilage repair
      compared to that of the incongruent joint.

PMID- 27716362
TI  - DNA replication stress: a source of APOBEC3B expression in breast cancer.
AB  - APOBEC cytidine deaminases have been implicated as major contributors to the
      mutation burden in many cancers on the basis of their mutational signature. A new
      experimental study sheds light on the inciting factors, linking APOBEC3B
      expression to oncogene- and drug-induced replication stress.

PMID- 27716361
TI  - Long non-coding RNA H19 regulates FOXM1 expression by competitively binding
      endogenous miR-342-3p in gallbladder cancer.
AB  - BACKGROUND: Long non-coding RNA (lncRNA) H19 has been reported to involve in many
      kinds of human cancers and functions as an oncogene. Our previous study found
      that H19 was over-expressed in gallbladder cancer (GBC) and was shown to promote
      tumor development in GBC. However, the competing endogenous RNA (ceRNA)
      regulatory network involving H19 in GBC progression has not been fully
      elucidated. We aim to detect the role of H19 as a ceRNA in GBC. METHODS AND
      RESULTS: In this study, the expression of H19 and miR-342-3p were analyzed in 35
      GBC tissues and matched normal tissues by using quantitative polymerase chain
      reaction (qRT-PCR). We demonstrated H19 was overexpressed and negatively
      correlated with miR-342-3p in GBC. By dual-luciferase reporter assays, RNA
      binding protein immunoprecipitation (RIP) and RNA pull-down assays, we verified
      that H19 was identified as a direct target of miR-342-3p. QRT-PCR and Western
      blotting assays demonstrated that H19 silencing down-regulated, whereas over
      expression enhanced the expression of miR-342-3p targeting FOXM1 through
      competitively 'sponging' miR-342-3p. Furthermore, transwell invasion assays and
      cell cycle assays indicated that H19 knockdown inhibited both cells invasion and
      proliferation, but this effects was attenuated by co-transfection of siRNA-H19
      and miR-342-3p inhibitor in GBC cells. In vivo, tumor volumes were decreased
      significantly in H19 silenced group compared to the control group, but was
      attenuated by co-transfection of shRNA-H19 and miR-342-3p inhibitor, which were
      stablely constructed through lenti-virus vector. CONCLUSION: Our results suggest
      a potential ceRNA regulatory network involving H19 regulates FOXM1 expression by
      competitively binding endogenous miR-342-3p in GBC. This mechanism may contribute
      to a better understanding of GBC pathogenesis and provides potential therapeutic
      strategy for GBC.

PMID- 27716363
TI  - Hyperchloremia is associated with 30-day mortality in major trauma patients: a
      retrospective observational study.
AB  - BACKGROUND: Chloride is important for maintaining acid-base balance, muscular
      activity, osmosis and immunomodulation. In patients with major trauma, chloride
      levels increase after fluid therapy; this is associated with poor clinical
      outcomes. The purpose of this study was to determine whether hyperchloremia was
      associated with increased mortality in patients who had sustained major trauma.
      METHODS: This study enrolled 266 major trauma patients by retrospective chart
      review, from January 2011 to December 2015. Patients were older than 16 years;
      were admitted to an intensive care unit; survived more than 48 h; and had
      sustained major trauma, defined as an injury severity score >= 16. Hyperchloremia
      was defined as a chloride level > 110mEq/L. Delta chloride (Deltachloride) was
      defined as the difference between the serum chloride level measured 48-h post
      admission and the initial level. Clinical and laboratory variables were compared
      between survivors (n = 235) and non-survivors (n = 31). A multivariate logistic
      regression analysis was performed to assess the association between
      hyperchloremia 48-h post-admission (hyperchloremia-48) and 30-day mortality.
      RESULTS: The overall 30-day mortality was 11.7 % (n = 31). Hyperchloremia-48
      occurred in 65 patients (24.4 %) and the incidence was significantly different
      between survivors and non-survivors (19.6 vs. 61.3 %, respectively, p < 0.001).
      Multivariate logistic analysis identified hyperchloremia-48 and Deltachloride as
      independent predictive factors for 30-day mortality in major trauma patients.
      DISCUSSION: Infusion of chloride-rich solutions, such as normal saline, is itself
      associated with hyperchloremia, which has been associated with poor patient
      outcomes. Patients receiving normal saline were more likely to suffer major
      postoperative complications, acute kidney injury, and infections. Moreover, large
      changes in serum chloride levels correlated with greater in-hospital mortality.
      CONCLUSION: Hyperchloremia 48-h post-admission and Deltachloride was associated
      with 30-day mortality in major trauma patients. These indices may be useful
      prognostic markers.

PMID- 27716364
TI  - Development and validation of a survey to measure features of clinical networks.
AB  - BACKGROUND: Networks of clinical experts are increasingly being implemented as a
      strategy to improve health care processes and outcomes and achieve change in the
      health system. Few are ever formally evaluated and, when this is done, not all
      networks are equally successful in their efforts. There is a need to formatively
      assess the strategic and operational management and leadership of networks to
      identify where functioning could be improved to maximise impact. This paper
      outlines the development and psychometric evaluation of an Internet survey to
      measure features of clinical networks and provides descriptive results from a
      sample of members of 19 diverse clinical networks responsible for evidence-based
      quality improvement across a large geographical region. METHODS: Instrument
      development was based on: a review of published and grey literature; a
      qualitative study of clinical network members; a program logic framework; and
      consultation with stakeholders. The resulting domain structure was validated for
      a sample of 592 clinical network members using confirmatory factor analysis.
      Scale reliability was assessed using Cronbach's alpha. A summary score was
      calculated for each domain and aggregate level means and ranges are reported.
      RESULTS: The instrument was shown to have good construct validity across seven
      domains as demonstrated by a high level of internal consistency, and all
      Cronbach's alpha coefficients were equal to or above 0.75. In the survey sample
      of network members there was strong reported commitment and belief in network-led
      quality improvement initiatives, which were perceived to have improved quality of
      care (72.8 %) and patient outcomes (63.2 %). Network managers were perceived to
      be effective leaders and clinical co-chairs were perceived as champions for
      change. Perceived external support had the lowest summary score across the seven
      domains. CONCLUSIONS: This survey, which has good construct validity and internal
      reliability, provides a valid instrument to use in future research related to
      clinical networks. The survey will be of use to health service managers to
      identify strengths and areas where networks can be improved to increase
      effectiveness and impact on quality of care and patient outcomes. Equally, the
      survey could be adapted for use in the assessment of other types of networks.

PMID- 27716365
TI  - Schistosomiasis vaccines: where do we stand?
AB  - Schistosomiasis, caused mainly by S. mansoni, S. haematobium and S. japonicum,
      continues to be a serious tropical disease and public health problem resulting in
      an unacceptably high level of morbidity in countries where it is endemic.
      Praziquantel, the only drug currently available for treatment, is unable to kill
      developing schistosomes, it does not prevent re-infection and its continued
      extensive use may result in the future emergence of drug-resistant parasites.
      This scenario provides impetus for the development and deployment of anti
      schistosome vaccines to be used as part of an integrated approach for the
      prevention, control and eventual elimination of schistosomiasis. This review
      considers the present status of candidate vaccines for schistosomiasis, and
      provides some insight on future vaccine discovery and design.

PMID- 27716366
TI  - The effect of n-3/n-6 polyunsaturated fatty acids on acute reflux esophagitis in
      rats.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFAs) play various roles in
      inflammation. However, the effect of PUFAs in the development of reflux
      esophagitis (RE) is unclear. This study is to investigate the potential effect of
      n-3/n-6 PUFAs on acute RE in rats along with the underlying protective
      mechanisms. METHODS: Forty Sprague Dawley rats were randomly divided into four
      groups (n = 10 in each group). RE model was established by pyloric clip and
      section ligation. Fish oil- and soybean oil-based fatty emulsion (n-3 and n-6
      groups), or normal saline (control and sham operation groups) was injected
      intraperitoneally 2 h prior to surgery and 24 h postoperatively (2 mL/kg,
      respectively). The expressions of interleukin (IL)-1beta, IL-8, IL-6 and myeloid
      differentiation primary response gene 88 (MyD88) in esophageal tissues were
      evaluated by Western blot and immunohistochemistry after 72 h. The
      malondialdehyde (MDA) and superoxide dismutase (SOD) expression in the esophageal
      tissues were determined to assess the oxidative stress. RESULTS: The mildest
      macroscopic/microscopic esophagitis was found in the n-3 group (P < 0.05). The
      expression of IL-1beta, IL-8, IL-6 and MyD88 were increased in all RE groups,
      while the lowest and highest expression were found in n-3 and n-6 group,
      respectively (P < 0.05). The MDA levels were increased in all groups (P < 0.05),
      in an ascending trend from n-3, n-6 groups to control group. The lowest and
      highest SOD levels were found in the control and n-3 group, respectively (P <
      0.05). CONCLUSION: n-3 PUFAs may reduce acute RE in rats, which may be due to
      inhibition of the MyD88-NF-kB pathway and limit oxidative damage.

PMID- 27716367
TI  - SDF-1/CXCR7 axis regulates the proliferation, invasion, adhesion, and
      angiogenesis of gastric cancer cells.
AB  - BACKGROUND: More recent studies have revealed that chemokine receptor CXCR7 plays
      an important role in cancer development. However, little is known about the
      effect of CXCR7 on the process of gastric cancer cell invasion and angiogenesis.
      The aim of this study is to investigate the expression of CXCR7 in gastric cancer
      cell lines and to evaluate the role of CXCR7 in the proliferation, invasion,
      adhesion, and angiogenesis of gastric cancer cells. METHODS: Real-time PCR and
      Western blotting were used to examine the mRNA and protein levels of CXCR4 and
      CXCR7 in five gastric cancer cell lines (HGC-27, MGC-803, BGC-823, SGC-7901, and
      MKN-28). CXCR7-expressing shRNA was constructed and subsequently stably
      transfected into the human gastric cancer cells. In addition, the effect of CXCR7
      inhibition on cell proliferation, invasion, adhesion, VEGF secretion, and tube
      formation was evaluated. RESULTS: The mRNA and protein of CXCR7 were expressed in
      all five gastric cancer cell lines; in particular, the expression of CXCR7 was
      the highest in SGC-7901 cells. Stromal cell-derived factor-1 (SDF-1) was found to
      induce proliferation, invasion, adhesion, and tube formation. Moreover, the VEGF
      secretion in SGC-7901 cells was also enhanced by SDF-1 stimulation. These
      biological effects were inhibited by the silencing of CXCR7 in SGC-7901 cells.
      CONCLUSIONS: Increased CXCR7 expression was found in gastric cancer cells.
      Knockdown of CXCR7 expression by transfection with CXCR7shRNA significantly
      inhibits SGC-7901 cells' proliferation, invasion, adhesion, and angiogenesis.
      This study provides new insights into the significance of CXCR7 in the invasion
      and angiogenesis of gastric cancer.

PMID- 27716368
TI  - A novel model for studying ileitis-induced visceral hypersensitivity in goats.
AB  - BACKGROUND: Visceral hypersensitivity (VH) is a common condition in many
      gastrointestinal disorders such as inflammatory bowel diseases (IBDs) in human
      and animals. Most studies often induce Crohn's disease/colitis to investigate VH
      in small experimental animals. Although farm animals commonly suffer from IBDs,
      their VH has not been investigated so far. Because goats can suffer from Johne's
      disease, a naturally occurring Crohn's-like disease, they may be suitable to be
      used for studying the mechanism underlying VH in common intestinal disorders of
      large animals. In the present study, 60 healthy goats of either sex were equally
      divided into a 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) group and saline
      group. A volume of 1.2 ml of TNBS-ethanol solution (30 mg TNBS in 40 % ethanol)
      or an equal volume of isotonic saline was injected into the wall of the terminal
      ileum through laparotomy. The severity of the developing ileitis was determined
      according to macro- and microscopic pathologic scores and the levels of
      myeloperoxidase, interleukin-1beta, interleukin-6 and tumor necrosis factor
      alpha, and VH was evaluated with visceromotor responses (VMR) to colorectal
      distension on days 3, 7, 14, 21 and 28. VMRs were assessed with a continuous ramp
      distention mode with 6 s for each pressure (20, 40, 60, 80 and 100 mmHg).
      RESULTS: Compared to the saline group, the TNBS-treated goats showed apparent
      transmural pathological changes and a significant increase (P < 0.05) in
      macroscopic and microscopic change scores, and levels of myeloperoxidase,
      interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha in the ileum,
      and VMR to colorectal distension. The goats exhibited apparent ileitis at days 3
      to 21, and VH at days 7 to 28 following TNBS treatment. CONCLUSION: This
      experiment successfully established a reproducible ileitis and VH with
      administration of TNBS-ethanol solution in the ileal wall of goats. This model is
      useful for studying the pathogenesis of the IBD and the mechanism underlying VH,
      and for evaluating the efficacy of new therapeutic regimens.

PMID- 27716370
TI  - Near-infrared spectroscopy for assessing tissue oxygenation and microvascular
      reactivity in critically ill patients: a prospective observational study.
AB  - BACKGROUND: Impaired microcirculatory perfusion and tissue oxygenation during
      critical illness are associated with adverse outcome. The aim of this study was
      to detect alterations in tissue oxygenation or microvascular reactivity and their
      ability to predict outcome in critically ill patients using thenar near-infrared
      spectroscopy (NIRS) with a vascular occlusion test (VOT). METHODS: Prospective
      observational study in critically ill adults admitted to a 12-bed intensive care
      unit (ICU) of a University Hospital. NIRS with a VOT (using a 40 % tissue oxygen
      saturation (StO2) target) was applied daily until discharge from the ICU or
      death. A group of healthy volunteers were evaluated in a single session. During
      occlusion, StO2 downslope was measured separately for the first (downslope 1) and
      last part (downslope 2) of the desaturation curve. The difference between
      downslope 2 and 1 was calculated (delta-downslope). The upslope and area of the
      hyperaemic phase (receive operating characteristic (ROC) area under the curve
      (AUC) of StO2) were calculated, reflecting microvascular reactivity. Outcomes
      were ICU and 90-day mortality. RESULTS: Patients (n = 89) had altered downslopes
      and upslopes compared to healthy volunteers (n = 27). Mean delta-downslope was
      higher in ICU non-survivors (2.8 (0.4, 3.8) %/minute versus 0.4 (-0.8, 1.8) in
      survivors, p = 0.004) and discriminated 90-day mortality (ROC AUC 0.72 (95 %
      confidence interval 0.59, 0.84)). ICU non-survivors had lower mean upslope (141
      (75, 193) %/minute versus 185 (143, 217) in survivors, p = 0.016) and AUC StO2
      (7.9 (4.3, 12.6) versus 14.5 (11.2, 21.3), p = 0.001). Upslope and AUC StO2 on
      admission were significant although weak predictors of 90-day mortality (ROC AUC
      = 0.68 (0.54, 0.82) and 0.70 (0.58, 0.82), respectively). AUC StO2 <= 6.65 (1st
      quartile) on admission was independently associated with higher 90-day mortality
      (hazard ratio 7.964 (95 % CI 2.211, 28.686)). The lowest upslope in the ICU was
      independently associated with survival after ICU discharge (odds ratio 0.970 (95
      % CI 0.945, 0.996)). CONCLUSIONS: In critically ill patients, NIRS with a VOT
      enables identification of alterations in tissue oxygen extraction capacity and
      microvascular reactivity that can predict mortality. TRIAL REGISTRATION:
      NCT02649088, www.clinicaltrials.gov , date of registration 23rd December 2015,
      retrospectively registered.

PMID- 27716371
TI  - The effect of suramin on inhibiting fibroblast proliferation and preventing
      epidural fibrosis after laminectomy in rats.
AB  - BACKGROUND: Epidural fibrosis often causes serious complications in patients
      after lumbar laminectomy and discectomy and is associated with the proliferation
      of fibroblasts. Suramin is known to have an obvious inhibitory effect on the
      coactions of many growth factors and their receptors, but little was previously
      known about the effect of suramin on fibroblast proliferation and the progress of
      epidural fibrosis. METHODS: We illustrated the effect of suramin on cultured
      fibroblasts of rats with different concentrations (0, 200, 400, 600 mg/l). The
      proliferation of suramin-treated fibroblasts was evaluated by CCK-8 and western
      blot analysis. Additionally, in a rat model of laminectomy, different
      concentrations of suramin (100, 200, and 300 mg/ml) and saline were applied to
      the laminectomy sites locally. The effect of suramin on preventing epidural
      fibrosis was detected by the Rydell classification, hydroxyproline content,
      histological analysis, and collagen density analyses. RESULTS: The results of CCK
      8 shown that suramin could significantly inhibit fibroblasts proliferation in a
      dose-dependent manner. The western blotting shown that the expression levels of
      the cell proliferation markers such as cyclin D1, cyclin E, and PCNA were down
      regulated. Moreover, in a rat model, we found that suramin could reduce epidural
      fibrosis as well as inhibit fibroblast proliferation, and 300 mg/ml suramin had
      better effect. CONCLUSIONS: Topical application of suramin could reduce epidural
      fibrosis after laminectomy, and the application of suramin could inhibit the
      proliferation of fibroblasts in rats. This study indicates that suramin is a
      potent antifibrotic agent that may have therapeutic potential for patients with
      epidural fibrosis.

PMID- 27716369
TI  - Patient survival and tumor characteristics associated with CHEK2:p.I157T -
      findings from the Breast Cancer Association Consortium.
AB  - BACKGROUND: P.I157T is a CHEK2 missense mutation associated with a modest
      increase in breast cancer risk. Previously, another CHEK2 mutation, the protein
      truncating c.1100delC has been associated with poor prognosis of breast cancer
      patients. Here, we have investigated patient survival and characteristics of
      breast tumors of germ line p.I157T carriers. METHODS: We included in the analyses
      26,801 European female breast cancer patients from 15 studies participating in
      the Breast Cancer Association Consortium. We analyzed the association between
      p.I157T and the clinico-pathological breast cancer characteristics by comparing
      the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors.
      Similarly, we investigated the p.I157T associated risk of early death, breast
      cancer-associated death, distant metastasis, locoregional relapse and second
      breast cancer using Cox proportional hazards models. Additionally, we explored
      the p.I157T-associated genomic gene expression profile using data from breast
      tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO:
      GSE24450). Differential gene expression analysis was performed using a moderated
      t test. Functional enrichment was investigated using the DAVID functional
      annotation tool and gene set enrichment analysis (GSEA). The tumors were
      classified into molecular subtypes according to the St Gallen 2013 criteria and
      the PAM50 gene expression signature. RESULTS: P.I157T was not associated with
      increased risk of early death, breast cancer-associated death or distant
      metastasis relapse, and there was a significant difference in prognosis
      associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore,
      p.I157T was associated with lobular histological type and clinico-pathological
      markers of good prognosis, such as ER and PR expression, low TP53 expression and
      low grade. Gene expression analysis suggested luminal A to be the most common
      subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be
      significantly enriched among genes, whose expression differed between p.I157T and
      non-carrier tumors. CONCLUSIONS: Our analyses suggest that there are fundamental
      differences in breast tumors of CHEK2:p.I157T and c.1100delC carriers. The poor
      prognosis associated with c.1100delC cannot be generalized to other CHEK2
      mutations.

PMID- 27716372
TI  - Should we treat pyrexia? And how do we do it?
AB  - The concept of pyrexia as a protective physiological response to aid in host
      defence has been challenged with the awareness of the severe metabolic stress
      induced by pyrexia. The host response to pyrexia varies, however, according to
      the disease profile and severity and, as such, the management of pyrexia should
      differ; for example, temperature control is safe and effective in septic shock
      but remains controversial in sepsis. From the reported findings discussed in this
      review, treating pyrexia appears to be beneficial in septic shock, out of
      hospital cardiac arrest and acute brain injury.Multiple therapeutic options are
      available for managing pyrexia, with precise targeted temperature management now
      possible. Notably, the use of pharmacotherapy versus surface cooling has not been
      shown to be advantageous. The importance of avoiding hypothermia in any treatment
      strategy is not to be understated.Whilst a great deal of progress has been made
      regarding optimal temperature management in recent years, further studies will be
      needed to determine which patients would benefit the most from control of pyrexia
      and by which means this should be implemented. This narrative review is part of a
      series on the pathophysiology and management of pyrexia.

PMID- 27716373
TI  - Real-time point of care microcirculatory assessment of shock: design, rationale
      and application of the point of care microcirculation (POEM) tool.
AB  - BACKGROUND: Despite over a decade of research and technological advances,
      sublingual microcirculatory monitoring has not yet reached clinical utility.
      Offline analysis is time consuming and occurs away from the patient. A system to
      assess the microcirculation at the point of care is desirable. We present a novel
      5-point grading system (the point of care microcirculation (POEM) scoring system)
      that can be used at the point of care during non-invasive sublingual
      microcirculatory monitoring. METHODS: The POEM score is an ordinal scale from 1
      (worst) to 5 (best), based on a composite assessment of flow and heterogeneity of
      four individual sublingual video-microscopy clips. Thirty-two healthcare
      professionals were trained in how to assign POEM scores. Following training they
      assigned scores to five test sequences (each consisting of four video clips).
      They were blinded to clinical status. Inter-user consistency and agreement were
      assessed using intra-class correlation coefficient (ICC) analysis. In addition,
      blinded expert scores for 68 video clips were compared to offline computer
      analysis using traditional microcirculatory parameters including total vessel
      density (TVD), perfused vessel density (PVD), proportion of perfused vessels
      (PPV), microcirculatory flow index (MFI) and microcirculatory heterogeneity index
      (MHI). The time taken to assign each was recorded. RESULTS: Participants showed
      good inter-rater consistency (ICC 0.83, 95 % CI 0.626, 0.976) and agreement (ICC
      0.815, 95 % CI 0.602, 0.974) for assigned POEM scores. Expert scoring of videos
      correlated with offline values for PVD (R 2  = 0.39; p < 0.05), PPV (R 2  = 0.71;
      p < 0.001), MFI (R 2  = 0.75; p < 0.001), and MHI (R 2  = 0.68; p < 0.001). POEM
      scores took less time to assign than conventional offline computer analysis (2
      minutes versus 44 minutes). CONCLUSION: We present for the first time a novel 5
      point ordinal scale of microcirculatory flow and heterogeneity that can be used
      at the point of care. It has minimal inter-user variability amongst healthcare
      professionals after just 1 hour of training. POEM scores take a short time to
      assign, and correspond well to traditional offline computer-analyzed parameters.

PMID- 27716374
TI  - Prevalence of Angiostrongylus vasorum in southern Belgium, a coprological and
      serological survey.
AB  - BACKGROUND: Canine angiostrongylosis, a gastropod-borne helminthic infection, is
      increasingly being described in North America and is now reported in many
      European countries. In dogs, Angiostrongylus vasorum may cause a wide spectrum of
      clinical signs. Respiratory distress such as coughing and dyspnoea are the most
      frequently described manifestations. The aim of the present study was to gain
      additional information on the distribution, prevalence and risk factors
      associated with A. vasorum infection in dog from southern Belgium through the
      combined used of a commercially available in-clinic assay for detection of
      circulating antigen (Angio DetectTM, IDEXX, Westbrook, USA) and coprology in two
      different canine populations: dogs with clinical signs compatible with
      angiostrongylosis and asymptomatic dogs or dogs presented for unrelated
      conditions (control). RESULTS: A total of 979 dogs were enrolled in the study
      from November 2014 until February 2016. Seven hundred fifty-seven dogs were
      included in the control group, whereas 222 dogs had clinical signs compatible
      with angiostrongylosis. Forty-six dogs out of 979 (4.7 %) had A. vasorum
      circulating antigen. There was a highly significant difference between the two
      populations (3.6 % (27/747) and 8.6 % (19/222) in control and symptomatic dogs,
      respectively) (P = 0.00379). First stage larvae (L1) of A. vasorum were found in
      seven out of 24 serologically positive control dogs and in six out of 17
      serologically positive symptomatic dogs. Interestingly, L1 of Crenosoma vulpis
      were detected by Baermann technique in one control and nine symptomatic dogs,
      respectively. Out of 17 Angio DetectTM (IDEXX, Westbrook, USA) positive dogs with
      negative (14) or not performed Baermann test (three), one dog was positive in
      both in-house ELISAs (Ag and Ab) and one dog was positive for Ag. Statistical
      analysis was unable to detect any risk factors associated with the direct and/or
      indirect detection of A. vasorum. CONCLUSIONS: This seroepidemiological study
      demonstrated for the first time a high seroprevalence in Southern Belgium for A.
      vasorum. The Angio DetectTM was found to be suitable in this context as the
      collection, preservation and examination of stools were difficult. Nevertheless,
      discrepancies were observed between the different available tests. Additional
      research is clearly needed. Also, coproscopy remains a very useful tool in dogs
      infected for less than nine weeks and for the identification of other canine lung
      nematodes such as C. vulpis. This study also demonstrates that asymptomatic dogs
      may shed A. vasorum L1 in their faeces and therefore contribute to the
      maintenance of A. vasorum life-cycle.

PMID- 27716375
TI  - Erratum to: A benchmark for RNA-seq quantification pipelines.

PMID- 27716376
TI  - Lipiodol retention pattern assessed by cone beam computed tomography during
      conventional transarterial chemoembolization of hepatocellular carcinoma:
      accuracy and correlation with response.
AB  - BACKGROUND: To investigate accuracy of intraprocedural cone beam computed
      tomography (CBCT) compared to fluoroscopy for detection of lipiodol retention
      pattern during conventional transarterial chemoembolization (cTACE) of
      hepatocellular carcinoma (HCC) and its correlation with short-term response.
      METHODS: Between September 2013 and July 2014, 29 patients with HCC underwent
      chemoembolization of 51 tumors (mean diameter 28.1 mm, range 10.0-136.3 mm).
      Lipiodol retention pattern was assessed by CBCT at the endpoint of cTACE compared
      by fluoroscopy. Depending on the pattern of tumor covered by lipiodol three
      classes were defined: complete (more than 90 %, no peripheral defects), moderate
      (50-90 %, some with or without peripheral defects), and poor (less than 50 %).
      Tumor response was assessed by modified Response Evaluation Criteria in Solid
      Tumors (mRECIST) based on follow-up contrast enhanced (CE) computed tomography
      (CT) or magnetic resonance imaging (MRI) obtained 4-6 weeks post-cTACE.
      Correlations between lipiodol retention patterns on CBCT and fluoroscopy as well
      as tumor response were assessed using multivariate logistic regression. RESULTS:
      Of 51 hepatic tumors, 40 (78.4 %) had complete response (CR); 8 (15.7 %) had
      partial response (PR); 1 (2.0 %) had stable disease (SD); and 2 (3.9 %) had
      progressive disease (PD). The degree of lipiodol retention scored excellent,
      moderate, and poor, in fluoroscopic images vs CBCT images were 23 (45.1 %) vs 39
      (76.5 %), 19 (37.3 %) vs 11 (21.6 %), and 9 (17.6 %) vs 1 (2.0 %), respectively.
      Lipiodol retention assessment with CBCT (Az = 0.75) is more accurate than
      fluoroscopy (Az = 0.54) in predicting target tumor response. Other than lipiodol
      retention pattern assessed with CBCT (p = 0.01), tumor size (p = 0.04) is an
      independent predictors of CR. CONCLUSION: CBCT is more accurate than fluoroscopy
      in classification of lipiodol retention pattern in HCC tumors at the time of
      cTACE. CBCT could be used as a reliable intra precedural monitoring modality of
      cTACE.

PMID- 27716378
TI  - Assessment of clinical trial participant patient satisfaction: a call to action.
AB  - BACKGROUND: As patient satisfaction scores become increasingly relevant in
      today's health care market, we sought to evaluate satisfaction of the unique
      subset of patients enrolling in clinical trials in a research facility embedded
      within a community hospital system. METHODS: We developed and deployed a patient
      satisfaction survey tailored to clinical trial patients who consented to and/or
      completed a clinical trial in our research institute in the prior year. The
      survey was distributed to 222 patients. Likert scale responses were analyzed
      using top box and percentile rank procedures. Correlation analysis was used to
      evaluate associations between the clinical trial experience and intent to return
      to our system for routine care. RESULTS: Ninety surveys were returned in the 6
      months following the mailing for a 41 % response rate; the bulk of these (N = 81)
      were returned within 6 weeks of the mailing. The questions with the highest
      ranking responses were related to interactions with staff (84th percentile or
      higher). Fifty-one point one percent of patients (64th percentile) strongly
      agreed that they would seek future care in our system. Patient intent to return
      to the provider seen during the clinical trial was most highly correlated with
      intent to seek future care within our system (r = 0.54, p < 0.0001). Reasons
      cited for clinical trial enrollment were generally altruistic. CONCLUSIONS:
      Querying this special patient population is feasible and yields valuable insight
      into their experience with healthcare system-based clinical trials and the
      relationship between clinical trial participation and perception of the
      healthcare system as a desirable resource for routine medical care. We argue that
      this work is invaluable to the research community and submit a call to action to
      our peers to begin systematic evaluation of clinical trial patient satisfaction.

PMID- 27716377
TI  - Urine biomarkers give early prediction of acute kidney injury and outcome after
      out-of-hospital cardiac arrest.
AB  - BACKGROUND: Post-resuscitation care after out-of-hospital cardiac arrest (OHCA)
      is challenging due to the threat of organ failure and difficult prognostication.
      Our aim was to examine whether urine biomarkers could give an early prediction of
      acute kidney injury (AKI) and outcome. METHODS: This was a prospective
      observational study of comatose OHCA patients at Oslo University Hospital
      Ulleval, Norway. Risk factors were clinical parameters and biomarkers measured in
      spot urine (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and the
      product of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like
      growth factor-binding protein 7 (IGFBP7)) at admission and day 3. Outcome
      variables were AKI within 3 days using the Kidney Disease Improving Global
      Outcomes definition, 6-month mortality, and poor neurological outcome (PNO)
      defined as cerebral performance category 3-5. RESULTS: Among 195 included
      patients (85 % males, mean age 60 years), 88 (45 %) died, 96 (49 %) had PNO, and
      88 (45 %) developed AKI. In univariate analysis, increased urine cystatin C and
      NGAL concentration sampled at admission and day 3 were independent risk factors
      for AKI, mortality and PNO. Increased urine TIMP-2 * IGFBP7 levels was associated
      with AKI only at admission. In multivariate analyses combining clinical
      parameters and biomarker concentrations, the area under the receiver operating
      characteristics curve (AuROC) with 95 % confidence interval (CI) were 0.774
      (0.700-0.848), 0.812 (0.751-0.873), and 0.819 (0.759-0.878) for AKI, mortality
      and PNO, respectively. CONCLUSIONS: In comatose OHCA patients, urine levels of
      cystatin C and NGAL at admission and day 3 were independent risk factors for AKI,
      6-month mortality and PNO. TRIAL REGISTRATION: Clinicaltrials.gov NCT01239420 .
      Registered 10 November 2010.

PMID- 27716379
TI  - Spinal cord injury: is monitoring from the injury site the future?
AB  - This paper challenges the current management of acute traumatic spinal cord
      injury based on our experience with monitoring from the injury site in the
      neurointensive care unit. We argue that the concept of bony decompression is
      inadequate. The concept of optimum spinal cord perfusion pressure, which differs
      between patients, is introduced. Such variability suggests individualized patient
      treatment. Failing to optimize spinal cord perfusion limits the entry of
      systemically administered drugs into the injured cord. We conclude that
      monitoring from the injury site helps optimize management and should be subjected
      to a trial to determine whether it improves outcome.

PMID- 27716380
TI  - A novel DNA/histone H4 peptide complex detects autoantibodies in systemic lupus
      erythematosus sera.
AB  - BACKGROUND: The detection of anti-dsDNA antibodies is critical for the diagnosis
      and follow-up of systemic lupus erythematosus (SLE) patients. The presently
      available assays are characterized by a non-optimal specificity (solid phase
      assays) or sensitivity (Crithidia Luciliae immunofluorescence test (CLIFT)). To
      overcome the limits of CLIFT and solid phase chromatin assays, we explored the
      diagnostic potential of an assay based on plasmid DNA containing a highly bent
      fragment of 211 bp from Crithidia Luciliae minicircles, complexed with histone
      peptides. METHODS: Electrically neutral complexes of PK201/CAT plasmid (PK) DNA
      and histone 4 (H4) peptides were evaluated by electromobility shift assay.
      Complexes of H4 peptides and PK were absorbed to the solid phase to detect
      specific immunoglobulin G (IgG) in sera. Sera from 109 SLE patients, 100 normal
      healthy subjects, and 169 disease controls were tested. RESULTS: H4(14-34)
      containing the consensus sequence for DNA binding interacts with PK, retarding
      its migration. H4(14-34)/PK complexes were used to test sera by ELISA. Anti-H4-PK
      antibodies were detected in 56 % of SLE sera (more frequently in patients with
      skin or joint involvement) versus 5.9 % in disease controls; inhibition assays
      show that sera react with epitopes present on DNA or on the complex, not on the
      peptide. Antibody titer is correlated with European Consensus Lupus Activity
      Measurement (ECLAM) score and anti-complement component 1q (C1q) antibodies,
      negatively with C3 levels. Anti-H4-PK antibodies compared with CLIFT and solid
      phase dsDNA assays display moderate concordance. CONCLUSIONS: The H4/PK assay is
      a simple and reliable test which is useful for the differential diagnosis and
      evaluation of disease activity in SLE patients.

PMID- 27716381
TI  - Improving outcomes for hospital patients with critical bleeding requiring massive
      transfusion: the Australian and New Zealand Massive Transfusion Registry study
      methodology.
AB  - BACKGROUND: The Australian and New Zealand (ANZ) Massive Transfusion (MT)
      Registry (MTR) has been established to improve the quality of care of patients
      with critical bleeding (CB) requiring MT (>= 5 units red blood cells (RBC) over 4
      h). The MTR is providing data to: (1) improve the evidence base for transfusion
      practice by systematically collecting data on transfusion practice and clinical
      outcomes; (2) monitor variations in practice and provide an opportunity for
      benchmarking, and feedback on practice/blood product use; (3) inform blood supply
      planning, inventory management and development of future clinical trials; and (4)
      measure and enhance translation of evidence into policy and patient blood
      management guidelines. The MTR commenced in 2011. At each participating site, all
      eligible patients aged >=18 years with CB from any clinical context receiving MT
      are included using a waived consent model. Patient information and clinical
      coding, transfusion history, and laboratory test results are extracted for each
      patient's hospital admission at the episode level. RESULTS: Thirty-two hospitals
      have enrolled and 3566 MT patients have been identified across Australia and New
      Zealand between 2011 and 2015. The majority of CB contexts are surgical, followed
      by trauma and gastrointestinal haemorrhage. Validation studies have verified that
      the definition of MT used in the registry correctly identifies 94 % of CB events,
      and that the median time of transfusion for the majority of fresh products is the
      'product event issue time' from the hospital blood bank plus 20 min. Data linkage
      between the MTR and mortality databases in Australia and New Zealand will allow
      comparisons of risk-adjusted mortality estimates across different bleeding
      contexts, and between countries. Data extracts will be examined to determine if
      there are differences in patient outcomes according to transfusion practice. The
      ratios of blood components (e.g. FFP:RBC) used in different types of critical
      bleeding will also be investigated. CONCLUSIONS: The MTR is generating data with
      the potential to have an impact on management and policy decision-making in CB
      and MT and provide benchmarking and monitoring tools for immediate application.

PMID- 27716382
TI  - Gender differences in outcomes following isolated coronary artery bypass
      grafting: long-term results.
AB  - BACKGROUND: The main purpose of this study was to evaluate the impact of gender
      on outcomes after isolated coronary artery bypass grafting, in terms of 5-year
      rates of overall death, cardiac-related death, myocardial infarction, re
      hospitalization, repeat percutaneous or surgical revascularization, stroke, new
      pacemaker implantation, postoperative renal failure, heart failure and need for
      long-term care. METHODS: Two propensity-score matched cohorts, each of 1331
      patients, undergoing isolated surgical coronary revascularization at the regional
      public and private centers of Emilia-Romagna region (Italy) from January 1st 2003
      to December 31th 2013, were used to compare long-term outcomes of male (5976
      patients) versus female gender (1332 patients). RESULTS: In the matched cohort,
      males received significantly more bypass grafts (3.0 +/- 1.0 vs 2.8 +/- 1.0, p =
      0.001). Left internal mammary artery use and total arterial revascularization
      were similarly performed in both matched subgroups. Both groups reported similar
      cumulative rate of all-cause, cardiac-related mortality and stroke at five years.
      Females experienced significantly higher rate of myocardial infarction, and not
      significantly higher occurrence of heart failure, and need for long-term care.
      Males experienced significantly higher rate of cumulative re-hospitalization and
      higher need for pacemaker implantation. Female gender was not an independent
      predictor of death at long-term follow-up. CONCLUSIONS: Women are more likely to
      be readmitted with myocardial infarction and congestive heart failure after CABG
      but experience survival similar to that observed in men. Female gender was not an
      independent risk factor for mortality. Prevention of new occurrence of
      postoperative myocardial infarction and enhancement of complete coronary
      revascularization should be future endpoints.

PMID- 27716383
TI  - Upregulation of neuronal zinc finger protein A20 expression is required for
      electroacupuncture to attenuate the cerebral inflammatory injury mediated by the
      nuclear factor-kB signaling pathway in cerebral ischemia/reperfusion rats.
AB  - BACKGROUND: Zinc finger protein A20 (tumor necrosis factor alpha-induced protein
      3) functions as a potent negative feedback inhibitor of the nuclear factor-kB (NF
      kB) signaling. It exerts these effects by interrupting the activation of IkB
      kinase beta (IKKbeta), the most critical kinase in upstream of NF-kB, and thereby
      controlling inflammatory homeostasis. We reported previously that
      electroacupuncture (EA) could effectively suppress IKKbeta activation. However,
      the mechanism underlying these effects was unclear. Therefore, the current study
      further explored the effects of EA on A20 expression in rat brain and
      investigated the possible mechanism of A20 in anti-neuroinflammation mediated by
      EA using transient middle cerebral artery occlusion (MCAO) rats. METHODS: Rats
      were treated with EA at the "Baihui (GV20)," "Hegu (L14)," and "Taichong (Liv3)"
      acupoints once a day starting 2 h after focal cerebral ischemia. The
      spatiotemporal expression of A20, neurobehavioral scores, infarction volumes,
      cytokine levels, glial cell activation, and the NF-kB signaling were assessed at
      the indicated time points. A20 gene interference (overexpression and silencing)
      was used to investigate the role of A20 in mediating the neuroprotective effects
      of EA and in regulating the interaction between neuronal and glial cells by
      suppressing neuronal NF-kB signaling during cerebral ischemia/reperfusion-induced
      neuroinflammation. RESULTS: EA treatment increased A20 expression with an earlier
      peak and longer lasting upregulation. The upregulated A20 protein was
      predominantly located in neurons in the cortical zone of the
      ischemia/reperfusion. Furthermore, neuronal A20 cell counts were positively
      correlated with neurobehavioral scores but negatively correlated with infarct
      volume, the accumulation of pro-inflammatory cytokines, and glial cell
      activation. Moreover, the effects of EA on improving the neurological outcome and
      suppressing neuroinflammation in the brain were reversed by A20 silencing.
      Finally, A20 silencing also suppressed the ability of EA to inhibit neuronal NF
      kB signaling pathway. CONCLUSIONS: Ischemia/reperfusion cortical neurons in MCAO
      rats are the main cell types that express A20, and there is a correlation between
      A20 expression and the suppression of neuroinflammation and the resulting
      neuroprotective effects. EA upregulated neuronal A20 expression, which played an
      essential role in the anti-inflammatory effects of EA by suppressing the neuronal
      NF-kB signaling pathway in the brains of MCAO rats.

PMID- 27716385
TI  - Complete nucleotide sequence of strawberry vein banding virus Chinese isolate and
      infectivity of its full-length DNA clone.
AB  - BACKGROUND: Strawberry vein banding virus (SVBV) is a double-stranded DNA plant
      virus, which has been found in North America, Australia, Brazil, Japan, Europe
      and several provinces of China. Infected strawberry plants exhibit mild vein
      banding symptoms and chlorosis along the veins. It is one of the most
      economically important diseases in Asiatic, European and North American
      strawberry-growing areas. FINDINGS: The complete genome of an SVBV Chinese
      isolate (SVBV-CN) was isolated and cloned from a naturally infected strawberry
      (Fragaria * ananassa cv. Sachinoka) sample found in Shenyang city of Liaoning
      province. Sequence analysis revealed a complete genome of 7864 nucleotides (nts)
      that indicated SVBV-CN was most closely related to SVBV from the United States
      (SVBV-US) with a sequence similarity of 85.8 %. Two major clades were identified
      based on phylogenetic analysis of the complete genome sequences of
      caulimoviruses. SVBV-CN clustered together with SVBV-US, whereas other
      caulimoviruses formed a separate branch. Agrobacterium-mediated inoculation of
      Fragaria vesca with an infectious clone of SVBV-CN results in systemic infection
      with distinct symptoms of yellowing bands along the main leaf veins. This
      suggests that the SVBV-CN infectious clone can recapitulate the symptoms observed
      in naturally infected strawberries, and therefore is likely the causal agent of
      the original disease observed in strawberries. Furthermore, strawberry plants
      inoculated with the infectious clone using vacuum infiltration developed symptoms
      with a very high infection rate of 86-100 % in 4-5 weeks post-inoculation. This
      compares to an infection rate of 20-40 % in 8-9 weeks post-inoculation using
      syringe-inoculation. CONCLUSIONS: The complete nucleotide sequence of SVBV from a
      naturally infected strawberry was determined. Agroinfiltration of strawberry
      plants using an infectious clone of SVBV-CN resulted in symptoms typically found
      in infected strawberries from Shenyang city of Liaoning province in China. This
      is the first report describing an infectious clone of SVBV-CN, and that vacuum
      infiltration can be potentially used as a new and highly efficient means for
      inoculation of strawberry plants.

PMID- 27716386
TI  - The production and sales of anti-tuberculosis drugs in China.
AB  - BACKGROUND: Tuberculosis (TB) is a major infectious disease globally. Adequate
      and proper use of anti-TB drugs is essential for TB control. This study aims to
      study China's production capacity and sales situation of anti-TB drugs, and to
      further discuss the potential for China to contribute to global TB control.
      METHODS: The production data of anti-TB drugs in China from 2011 to 2013 and the
      sales data from 2010 to 2014 were extracted from Ministry of Industry and
      Information Technology database of China and IMS Health database, respectively.
      The number of drugs was standardized to the molecular level of the key components
      before calculating. All data were described and analyzed by Microsoft Excel.
      RESULTS: First-line drugs were the majority in both sales (89.5 %) and production
      (92.3 %) of anti-TB drugs in China. The production of rifampicin held the
      majority share in active pharmaceutical ingredients (APIs) and finished products,
      whilst ethambutol and pyrazinamide were the top two sales in finished products.
      Fixed-dose combinations only held small percentages in total production and sales
      weight, though a slight increase was observed. The production and sales of
      streptomycin showed a tendency of decrease after 2012. The trends and proportion
      of different anti-TB drugs were similar in production and sales, however, the
      production weight was much larger than that of sales, especially for rifampicin
      and isoniazid. CONCLUSIONS: First-line drugs were the predominant medicine
      produced and used in China. While the low production and sales of the second-line
      TB drugs and FDCs rose concerns for the treatment of multiple drug resistant TB.
      The redundant production amount, as well as the prompt influence of national
      policy on drug production and sales, indicated the potential for China to better
      contribute to global TB control.

PMID- 27716384
TI  - Ion channels expression and function are strongly modified in solid tumors and
      vascular malformations.
AB  - BACKGROUND: Several cellular functions relate to ion-channels activity.
      Physiologically relevant chains of events leading to angiogenesis, cell cycle and
      different forms of cell death, require transmembrane voltage control. We
      hypothesized that the unordered angiogenesis occurring in solid cancers and
      vascular malformations might associate, at least in part, to ion-transport
      alteration. METHODS: The expression level of several ion-channels was analyzed in
      human solid tumor biopsies. Expression of 90 genes coding for ion-channels
      related proteins was investigated within the Oncomine database, in 25 independent
      patients-datasets referring to five histologically-different solid tumors
      (namely, bladder cancer, glioblastoma, melanoma, breast invasive-ductal cancer,
      lung carcinoma), in a total of 3673 patients (674 control-samples and 2999 cancer
      samples). Furthermore, the ion-channel activity was directly assessed by
      measuring in vivo the electrical sympathetic skin responses (SSR) on the skin of
      14 patients affected by the flat port-wine stains vascular malformation, i.e., a
      non-tumor vascular malformation clinical model. RESULTS: Several ion-channels
      showed significantly increased expression in tumors (p < 0.0005); nine genes
      (namely, CACNA1D, FXYD3, FXYD5, HTR3A, KCNE3, KCNE4, KCNN4, CLIC1, TRPM3) showed
      such significant modification in at least half of datasets investigated for each
      cancer type. Moreover, in vivo analyses in flat port-wine stains patients showed
      a significantly reduced SSR in the affected skin as compared to the contralateral
      healthy skin (p < 0.05), in both latency and amplitude measurements. CONCLUSIONS:
      All together these data identify ion-channel genes showing significantly modified
      expression in different tumors and cancer-vessels, and indicate a relevant
      electrophysiological alteration in human vascular malformations. Such data
      suggest a possible role and a potential diagnostic application of the ion
      electron transport in vascular disorders underlying tumor neo-angiogenesis and
      vascular malformations.

PMID- 27716387
TI  - Extreme hypernatremia as a probable cause of fatal arrhythmia: a case report.
AB  - BACKGROUND: Hypernatremia is a frequent occurrence among hospitalized patients.
      Severe hypernatremia is associated with mortality rates of over 60 %. Extreme
      hypernatremia, defined as sodium levels >190 mmol/l, is a rare occurrence. The
      literature on electrocardiographic changes occurring with this degree of
      hypernatremia is extremely scarce. We report the case of an 11-year-old Sri
      Lankan girl who presented with sodium levels of 226 mmol/l following infusion
      with 3 % hypertonic saline who developed diffuse QT prolongation leading to fatal
      ventricular tachycardia. CASE PRESENTATION: An 11-year-old Sri Lankan girl
      presented with fever, headache, vomiting, and altered level of consciousness.
      Following admission she developed generalized tonic-clonic seizures and was
      intubated and ventilated. She had a recent history of polyuria and polydipsia.
      Magnetic resonance imaging of her brain revealed hydrocephalus due to possible
      craniopharyngioma. A ventriculoperitoneal shunt was inserted and she was infused
      with 3 % hypertonic saline in an attempt to reduce intracranial pressure. The
      following day she became polyuric and dehydrated with tachycardia and low blood
      pressure. Biochemistry revealed serum sodium of 226 mmol/l, measured serum
      osmolality of 470 mOsm/kg, urine osmolality of 280 mOsm/kg, urine spot sodium of
      116 mmol/l, blood urea of 8.1 mmol/l, and blood glucose of 8.5 mmol/l. Her serum
      potassium, calcium, and magnesium levels were normal. Extreme hypernatremia due
      to infusion of 3 % hypertonic saline in the background of cranial diabetes
      insipidus was considered. She was managed aggressively with 5 % dextrose infusion
      and clear water via nasogastric feeding to correct the fluid deficit of 7 liters
      over 36 hours. Her sodium levels dropped to 160 mmol/l the following day.
      However, she developed electrocardiographic changes with widespread gross QT
      prolongation with ST segment deviations followed by fatal ventricular
      tachycardia. CONCLUSIONS: Extreme hypernatremia is rare, and the literature on
      electrocardiographic changes occurring at such high levels of sodium is scarce.
      At present there are no established guidelines on rate and mode of correction of
      such high sodium levels. This case highlights the electrocardiographic changes
      observed during extreme hypernatremia, controversies in managing increased
      intracranial pressure with hypertonic saline, and dilemmas encountered in
      managing extreme hypernatremia.

PMID- 27716388
TI  - The genetics of breast cancer risk in the post-genome era: thoughts on study
      design to move past BRCA and towards clinical relevance.
AB  - More than 12 % of women will be diagnosed with breast cancer in their lifetime.
      Although there have been tremendous advances in elucidating genetic risk factors
      underlying both familial and sporadic breast cancer, much of the genetic
      contribution to breast cancer etiology remains unknown. The discovery of BRCA1
      and BRCA2 over 20 years ago remains the seminal event in the field and has paved
      the way for the discovery of other high-penetrance susceptibility genes by
      linkage analysis. The advent of genome-wide association studies made possible the
      next wave of discoveries, in which over 80 low-penetrance and moderate-penetrance
      variants were identified. Although these studies were highly successful at
      discovering variants associated with both familial and sporadic breast cancer,
      the variants identified to date explain only 50 % of the heritability of breast
      cancer. In this review, we look back at the investigative strategies that have
      led to our current understanding of breast cancer genetics, consider the
      challenges of performing association studies in heterogeneous complex diseases
      such as breast cancer, and look ahead toward the types of study designs that may
      lead to the identification of the genetic variation accounting for the remaining
      missing heritability.

PMID- 27716389
TI  - Recurrent patent infections with Toxocara canis in household dogs older than six
      months: a prospective study.
AB  - BACKGROUND: To reduce environmental contamination with Toxocara canis eggs, the
      current general advice is to deworm all dogs older than six months on average
      four times a year. However, only a small proportion of non-juvenile household
      dogs actually shed T. canis eggs, and some dogs shed eggs more frequently than
      others. The identification of these frequent shedders and the associated risk
      factors is an important cornerstone for constructing evidence-based deworming
      regimens. The purpose of this study is to identify risk factors associated with
      recurrence of periods of shedding Toxocara eggs in a cohort of household dogs
      older than six months. METHODS: We performed a prospective study (July 2011 to
      October 2014) on shedding Toxocara eggs in a cohort of 938 household dogs older
      than six months from all over the Netherlands. The median follow-up time was 14
      months. Monthly, owners sent faecal samples of their dogs for Toxocara testing
      and completed a questionnaire. Dogs were dewormed only after diagnosis of a
      patent infection (PI). Survival analysis was used to assess factors influencing
      the time to first diagnosed PIs (FPI) and the time to recurrent PIs (RPI).
      RESULTS: The overall prevalence of PIs was 4.5 %, resulting in an estimated
      average incidence of 0.54 PIs/dog/year. No PI was diagnosed in 67.9 % of the
      dogs, 17.5 % of the dogs went through only one PI and 14.6 % had > 1 PI.
      Prevalence of PIs always peaked during wintertime. Increased hazards for first
      diagnosed PIs were associated with coprophagy, geophagy, walking off-leash for >=
      80 % of walking time, reported worms in the faeces, feeding a commercial diet and
      suffering from urologic or respiratory conditions. Median time to reinfection was
      nine months. Factors associated with increased hazards for recurrent PIs were
      taking corticosteroids, changing dog's main purpose, and proxies for veterinary
      care-seeking behaviours. CONCLUSIONS: We concluded that targeted anthelmintic
      treatments in household dogs may be feasible as PIs tend to (re)occur in specific
      periods and in groups of dogs at high risk. Moreover, recurrent PIs appear to be
      influenced more by factors related to impaired immunity than environmental
      exposure to Toxocara eggs.

PMID- 27716390
TI  - The organisation of physiotherapy for people with multiple sclerosis across
      Europe: a multicentre questionnaire survey.
AB  - BACKGROUND: Understanding the organisational set-up of physiotherapy services
      across different countries is increasingly important as clinicians around the
      world use evidence to improve their practice. This also has to be taken into
      consideration when multi-centre international clinical trials are conducted. This
      survey aimed to systematically describe organisational aspects of physiotherapy
      services for people with multiple sclerosis (MS) across Europe. METHODS:
      Representatives from 72 rehabilitation facilities within 23 European countries
      completed an online web-based questionnaire survey between 2013 and 2014.
      Countries were categorised according to four European regions (defined by United
      Nations Statistics). Similarities and differences between regions were examined.
      RESULTS: Most participating centres specialized in rehabilitation (82 %) and
      neurology (60 %), with only 38 % specialising in MS. Of these, the Western based
      Specialist MS centres were predominately based on outpatient services (median MS
      inpatient ratio 0.14), whilst the Eastern based European services were mostly
      inpatient in nature (median MS inpatient ratio 0.5). In almost all participating
      countries, medical doctors - specialists in neurology (60 %) and in
      rehabilitation (64 %) - were responsible for referral to/prescription of
      physiotherapy. The most frequent reason for referral to/prescription of
      physiotherapy was the worsening of symptoms (78 % of centres). Physiotherapists
      were the most common members of the rehabilitation team; comprising 49 % of the
      team in Eastern countries compared to approximately 30 % in the rest of Europe.
      Teamwork was commonly adopted; 86 % of centres based in Western countries
      utilised the interdisciplinary model, whilst the multidisciplinary model was
      utilised in Eastern based countries (p = 0.046). CONCLUSION: This survey is the
      first to provide data about organisational aspects of physiotherapy for people
      with MS across Europe. Overall, care in key organisational aspects of service
      provision is broadly similar across regions, although some variations, for
      example the models of teamwork utilised, are apparent. Organisational framework
      specifics should be considered anytime a multi-centre study is conducted and
      results from such studies are applied.

PMID- 27716391
TI  - Toll-like receptor 2 (TLR2) plays a role in controlling cutaneous leishmaniasis
      in vivo, but does not require activation by parasite lipophosphoglycan.
AB  - BACKGROUND: Leishmaniasis is a neglected tropical disease affecting millions of
      individuals worldwide. Despite several studies reporting involvement of the
      innate immune receptor Toll-like receptor 2 (TLR2) in the recognition of surface
      glycolipids from Leishmania parasites in vitro, the role of TLR2 and its co
      receptors during cutaneous leishmaniasis infection in vivo is unknown. METHODS:
      To explore the role of TLR2 and its co-receptors in cutaneous leishmaniasis, mice
      deficient in either TLR2, 4, 1 or 6, or wild-type (WT) controls, were infected
      with either Leishmania major promastigotes, L. mexicana promastigotes, L.
      mexicana amastigotes, or LPG1 -/- L. mexicana promastigotes. For each infection,
      lesion sizes were monitored and parasite burden was assessed at various time
      points. To assess immune responses, draining lymph node (DLN) cells were re
      stimulated with parasite antigens and the production of cytokines and parasite
      specific antibody isotypes in blood was determined by ELISA. RESULTS: Mice
      deficient in TLR2 and TLR4 presented with larger lesions and higher parasite
      burdens than WT controls. Mice lacking TLR2 co-receptors TLR1 or TLR6 did not
      show exacerbated infection, suggesting that TLR2 does not require either co
      receptor in the recognition of Leishmania infection. Furthermore, it appears that
      lipophosphoglycan (LPG) is not the major mediator of TLR2 activation during
      infection with L. mexicana, as parasites lacking LPG (axenic amastigotes and LPG1
      -/- promastigotes) also resulted in exacerbated disease in TLR2-/- mice. Infected
      TLR2-/- mice show a skewed Th2 immune response to Leishmania parasites, as
      demonstrated by elevated IL-4, IL-13 and IL-10 production by DLN cells from L.
      mexicana infected mice in response to antigen. Furthermore, L. major infected
      TLR2-/- mice have elevated antigen-specific IgG1 antibodies. CONCLUSIONS: TLR2
      deficiency leads to exacerbation of disease and parasite burden through promotion
      of Th2 immunity. TLR2 activation in vivo occurs independently of parasite LPG,
      suggesting other parasite ligands are involved in TLR2 recognition of Leishmania.

PMID- 27716392
TI  - Genetic variability and spatial distribution in small geographic scale of Aedes
      aegypti (Diptera: Culicidae) under different climatic conditions in Northeastern
      Brazil.
AB  - BACKGROUND: The study of the genetic structure of Aedes aegypti is essential to
      understanding their population dynamics as well as for the analysis of factors
      responsible for their resistance and ecological adaptation. The use of molecular
      markers in identifying differences amongst populations of Ae. aegypti in
      different geographical areas as well as the temporal variation of the vector
      populations has contributed to the improvement of vector control strategies. The
      present study aims to determine the genetic variability of Ae. aegypti
      populations in a small geographical area (state of Sergipe, Northeastern Brazil)
      by means of inter-simple sequence repeat (ISSR) and single nucleotide
      polymorphism (SNP) molecular markers. RESULTS: ISSR markers revealed a more
      heterogeneous pattern of genetic diversity among the populations with an expected
      heterozygosity (H E) ranging from 0.261 +/- 0.03 to 0.120 +/- 0.032, while a
      similar trend was detected through SNPs across populations with an H E between
      0.375 +/- 0.054 and 0.269 +/- 0.042. The population's genetic differentiation
      assessed with ISSR and SNP markers indicated a very low structuring among the
      populations with the highest diversity observed within the populations 72 %
      (ISSR) and 92 % (SNP). Clustering analysis also suggested little variation among
      populations: the seven populations were grouped into only three ISSR clusters and
      a single panmictic group based on SNP markers. The present study identified a
      close relationship between the populations, which probably results mainly from
      passive gene flow between mosquitoes from distinct geographic regions, influenced
      by humans commuting along roads. CONCLUSIONS: There was an intense migration of
      mosquitos across municipalities, leading to a potential increase in risk of
      arbovirus and insecticide resistance associated-alleles spreading between
      mosquito populations.

PMID- 27716394
TI  - Germline, hematopoietic, mosaic, and somatic variation: interplay between
      inherited and acquired genetic alterations in disease assessment.
AB  - Advances in genetic analysis have revealed new complexities in the interpretation
      of genetic variants. Correct assessment of a genetic variant relies on the
      clinical context and knowledge of the underlying biology. We outline four
      scenarios encountered in genetic testing where careful consideration of the
      origin of genetic variation is required for variant interpretation.

PMID- 27716393
TI  - Topological analysis of metabolic networks integrating co-segregating
      transcriptomes and metabolomes in type 2 diabetic rat congenic series.
AB  - BACKGROUND: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in
      type 2 diabetes mellitus occurs through complex organ-specific cellular
      mechanisms and networks contributing to impaired insulin secretion and insulin
      resistance. Genome-wide gene expression profiling systems can dissect the genetic
      contributions to metabolome and transcriptome regulations. The integrative
      analysis of multiple gene expression traits and metabolic phenotypes (i.e.,
      metabotypes) together with their underlying genetic regulation remains a
      challenge. Here, we introduce a systems genetics approach based on the
      topological analysis of a combined molecular network made of genes and
      metabolites identified through expression and metabotype quantitative trait locus
      mapping (i.e., eQTL and mQTL) to prioritise biological characterisation of
      candidate genes and traits. METHODS: We used systematic metabotyping by 1H NMR
      spectroscopy and genome-wide gene expression in white adipose tissue to map
      molecular phenotypes to genomic blocks associated with obesity and insulin
      secretion in a series of rat congenic strains derived from spontaneously diabetic
      Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a
      network biology strategy approach to visualize the shortest paths between
      metabolites and genes significantly associated with each genomic block. RESULTS:
      Despite strong genomic similarities (95-99 %) among congenics, each strain
      exhibited specific patterns of gene expression and metabotypes, reflecting the
      metabolic consequences of series of linked genetic polymorphisms in the congenic
      intervals. We subsequently used the congenic panel to map quantitative trait loci
      underlying specific mQTLs and genome-wide eQTLs. Variation in key metabolites
      like glucose, succinate, lactate, or 3-hydroxybutyrate and second messenger
      precursors like inositol was associated with several independent genomic
      intervals, indicating functional redundancy in these regions. To navigate through
      the complexity of these association networks we mapped candidate genes and
      metabolites onto metabolic pathways and implemented a shortest path strategy to
      highlight potential mechanistic links between metabolites and transcripts at
      colocalized mQTLs and eQTLs. Minimizing the shortest path length drove
      prioritization of biological validations by gene silencing. CONCLUSIONS: These
      results underline the importance of network-based integration of multilevel
      systems genetics datasets to improve understanding of the genetic architecture of
      metabotype and transcriptomic regulation and to characterize novel functional
      roles for genes determining tissue-specific metabolism.

PMID- 27716395
TI  - Thymosin beta4 and beta10 in Sjogren's syndrome: saliva proteomics and minor
      salivary glands expression.
AB  - BACKGROUND: In the present study, we investigated whether thymosin beta (Tbeta)
      in saliva and in minor salivary glands is differentially expressed in patients
      with primary Sjogren's syndrome (pSS) and patients with autoimmune diseases
      (systemic sclerosis [SSc], systemic lupus erythematosus [SLE], and rheumatoid
      arthritis [RA], with and without sicca syndrome [ss]). METHODS: Saliva specimens
      of nine patients with pSS, seven with ss/SSc, seven with ss/SLE, seven with
      ss/RA, seven with SSc, seven with SLE, and seven with RA, as well as ten healthy
      subjects, were analyzed using a high-performance liquid chromatograph coupled
      with a mass spectrometer equipped with an electrospray ionization source to
      investigate the presence and levels of Tbeta4, Tbeta4 sulfoxide, and Tbeta10.
      Immunostaining for Tbeta4 and Tbeta10 was performed on minor salivary glands of
      patients with pSS and ss. RESULTS: Tbeta4 levels were statistically higher in
      patients with pSS with respect to the other subgroups. Tbeta10 was detectable in
      66.7 % of patients with pSS and in 42.8 % of those with ss/SSc, while Tbeta4
      sulfoxide was detectable in 44.4 % of patients with pSS and in 42.9 % of those
      with ss/SSc. Tbeta10 and Tbeta4 sulfoxide were not detectable in patients without
      associated ss and in healthy control subjects. Regarding thymosin immunostaining,
      all patients had immunoreactivity for Tbeta10, and a comparable distribution
      pattern in the four different subgroups of patients was observed. Tbeta4
      immunoreactivity was present in patients with ss/SSc and those with ss/SLE, while
      it was completely absent in patients with pSS and those with ss/RA. CONCLUSIONS:
      Our data show that higher salivary Tbeta expression characterizes patients with
      pSS, while Tbeta4 sulfoxide and Tbeta10 salivary expression was selectively
      present in patients with sicca symptoms. Moreover, at the immunohistochemical
      level in patients with pSS, minor salivary glands showed a peculiar pattern
      characterized by immunostaining for Tbeta10 in acinar cells in the absence of any
      reactivity for Tbeta4. These findings, taken together, suggest a different role
      for Tbeta4 and Tbeta10 in patients with pSS who have ss and other autoimmune
      disease.

PMID- 27716396
TI  - Glucocorticoid-induced leucine zipper (GILZ) is involved in glucocorticoid
      induced and mineralocorticoid-induced leptin production by osteoarthritis
      synovial fibroblasts.
AB  - BACKGROUND: Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the
      anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not
      impair the anti-inflammatory activities of exogenous glucocorticoids in mice
      arthritis models and GILZ could also mediate some glucocorticoid-related adverse
      events. Osteoarthritis (OA) is a metabolic disorder that is partly attributed to
      adipokines such as leptin, and we previously observed that glucocorticoids
      induced leptin secretion in OA synovial fibroblasts. The purpose of this study
      was to position GILZ in OA through its involvement in the anti-inflammatory
      activities of glucocorticoids and/or in the metabolic pathway of leptin
      induction. The influences of mineralocorticoids on GILZ and leptin expression
      were also investigated. METHODS: Human synovial fibroblasts were isolated from OA
      patients during knee replacement surgery. Then, the cells were treated with a
      glucocorticoid (prednisolone), a mineralocorticoid (aldosterone), a
      glucocorticoid receptor (GR) antagonist (mifepristone), a selective
      glucocorticoid receptor agonist (Compound A), mineralocorticoid receptor (MR)
      antagonists (eplerenone and spironolactone), TNF-alpha or transforming growth
      factor (TGF)-beta. Cells were transfected with shRNA lentiviruses for the
      silencing of GILZ and GR. The leptin, IL-6, IL-8 and matrix metalloproteinase
      (MMP)-1 levels were measured by ELISA. Leptin, the leptin receptor (Ob-R), GR and
      GILZ expression levels were analyzed by western blotting and/or RT-qPCR. RESULTS:
      (1) The glucocorticoid prednisolone and the mineralocorticoid aldosterone induced
      GILZ expression dose-dependently in OA synovial fibroblasts, through GR but not
      MR. Similar effects on leptin and Ob-R were observed: leptin secretion and Ob-R
      expression were also induced by prednisolone and aldosterone through GR; (2) GILZ
      silencing experiments demonstrated that GILZ was involved in the glucocorticoid
      induced and mineralocorticoid-induced leptin secretion and Ob-R expression in OA
      synovial fibroblasts; and (3) GILZ inhibition did not alter the production of pro
      inflammatory cytokines by OA synovial fibroblast or the anti-inflammatory
      properties of glucocorticoids. CONCLUSIONS: The absence of GILZ prevents
      corticoid-induced leptin and Ob-R expression without affecting the anti
      inflammatory properties of glucocorticoids in OA synovial fibroblasts.
      Mineralocorticoids also induce leptin and Ob-R expression through GILZ.

PMID- 27716397
TI  - A20 suppresses canonical Smad-dependent fibroblast activation: novel function for
      an endogenous inflammatory modulator.
AB  - BACKGROUND: The ubiquitin-editing cytosolic enzyme A20, the major negative
      regulator of toll-like receptor (TLR)-mediated cellular inflammatory responses,
      has tight genetic linkage with systemic sclerosis (SSc). Because recent studies
      implicate endogenous ligand-driven TLR signaling in SSc pathogenesis, we sought
      to investigate the regulation, role and mechanism of action of A20 in skin
      fibroblasts. METHOD: A20 expression and the effects of forced A20 expression or
      siRNA-mediated A20 knockdown on fibrotic responses induced by transforming growth
      factor-beta (TGF-beta) were evaluated was evaluated in explanted human skin
      fibroblasts. Additionally, A20 regulation by TGF-beta, and by adiponectin, a
      pleiotropic adipokine with anti-fibrotic activity, was evaluated. RESULTS: In
      normal fibroblasts, TGF-beta induced sustained downregulation of A20, and
      abrogated its TLR4-dependent induction. Forced expression of A20 aborted the
      stimulation of collagen gene expression and myofibroblast transformation induced
      by TGF-beta, and disrupted canonical Smad signaling and Smad-dependent
      transcriptional responses. Conversely, siRNA-mediated knockdown of A20 enhanced
      the amplitude of fibrotic responses elicited by TGF-beta. Adiponectin, previously
      shown to block TLR-dependent fibrotic responses, elicited rapid and sustained
      increase in A20 accumulation in fibroblasts. CONCLUSION: These results identify
      the ubiquitin-editing enzyme A20 as a novel endogenous mechanism for negative
      regulation of fibrotic response intensity. Systemic sclerosis-associated genetic
      variants of A20 that cause impaired A20 expression or function, combined with
      direct suppression of A20 by TGF-beta within the fibrotic milieu, might play a
      significant functional role in persistence of fibrotic responses, while
      pharmacological augmentation of A20 inhibitory pathway activity might represent a
      novel therapeutic strategy.

PMID- 27716398
TI  - Challenges in and lessons learned during the implementation of the 1-3-7 malaria
      surveillance and response strategy in China: a qualitative study.
AB  - BACKGROUND: China has made great progress in malaria control over the last
      century and now aims to eliminate malaria by 2020. In 2012, the country launched
      its 1-3-7 surveillance and response strategy for malaria elimination. The
      strategy involves to case reporting within 1 day, case investigation within 3
      days, and focus investigation and public health actions within 7 days. The aim of
      this study was to evaluate the challenges in and lessons learned during the
      implementation of the 1-3-7 strategy in China so far. METHODS: This qualitative
      study was conducted in two provinces in China: Gansu province (northwestern
      China) and Jiangsu province (southeastern China) in 2014. Key informant
      interviews (n = 6) and in-depth interviews (n = 36) about the implementation
      aspects of the 1-3-7 strategy were conducted with malaria experts, health staff,
      laboratory practitioners, and village doctors at the provincial, city, county,
      township, and village levels. RESULTS: Broad themes related to the challenges in
      and lessons learned during the implementation of the 1-3-7 strategy were
      identified according to: case reporting within 1 day, case investigation within 3
      days, focus investigation within 7 days, and the overall strategy. The major
      challenges outlined were related to respecting the timeline of surveillance
      procedures, the absence of or difficulties in following guidelines on conducting
      focus investigations, diagnostics, and the increasing number of returning migrant
      workers from malaria-endemic countries. Important lessons learned revolve around
      the importance of continuous capacity building, supervision and motivation,
      quality control, information technology support, applied research, governmental
      commitment, and intersectoral collaboration. CONCLUSIONS: Surveillance is a key
      intervention in malaria elimination programs. The Chinese 1-3-7 strategy has
      already proven to be successful but still needs to be improved. In particular,
      dealing appropriately with imported malaria cases through the screening of
      migrant workers from malaria-endemic countries is essential for achieving and
      sustaining malaria elimination in China. China has perfect preconditions for
      successful malaria elimination provided political commitment and financial
      investment are guaranteed. The 1-3-7 strategy may also be considered as a model
      for other countries.

PMID- 27716399
TI  - Continuous evolution of clinical phenotype in 578 Japanese patients with Behcet's
      disease: a retrospective observational study.
AB  - BACKGROUND: It has been suggested that the phenotypes of Behcet's disease (BD) in
      Japan are changing. To ask whether the evolution of BD holds true in recent-onset
      cases in Japan, we performed a retrospective study. METHODS: We reviewed the
      records of 578 patients with BD who met the 1987 revised diagnostic criteria of
      the Behcet's disease research committee of Japan. The patients were divided into
      three groups based on the date of disease onset. We compared the demography,
      clinical features, and treatments among them with or without adjustment for the
      observation period. Patients having oral ulcers, genital ulcers, regional skin
      involvement, and uveitis are categorized as having complete-type BD, and the
      associated factors were determined by univariate and multivariate logistic
      regression analyses. RESULTS: Male patients had a higher propensity for uveitis
      and central nervous system (CNS) involvement, whereas female patients had higher
      rates of genital ulcers and arthritis. We found a significant trend in reduction
      of complete-type, genital ulcer, HLA-B51 carriers, and increment of
      gastrointestinal BD over time. Multiple regression analysis identified HLA-B51
      positivity, earlier date of disease onset, and younger age of onset as
      independently associated with complete-type BD. Although treatments had been also
      chronologically changed, the causative relationship between therapeutic agents
      and phenotypical changes was not determined from the study. CONCLUSION: The
      present study revealed that phenotypical evolution was characterized by decreased
      incidence of the complete type and increment of gastrointestinal involvement in
      Japanese patients with BD during the last 30 years.

PMID- 27716400
TI  - PERK regulates Gq protein-coupled intracellular Ca2+ dynamics in primary cortical
      neurons.
AB  - PERK (EIF2AK3) is an ER-resident eIF2alpha kinase required for behavioral
      flexibility and metabotropic glutamate receptor-dependent long-term depression
      via its translational control. Motivated by the recent discoveries that PERK
      regulates Ca2+ dynamics in insulin-secreting beta-cells underlying glucose
      stimulated insulin secretion, and modulates Ca2+ signals-dependent working
      memory, we explored the role of PERK in regulating Gq protein-coupled Ca2+
      dynamics in pyramidal neurons. We found that acute PERK inhibition by the use of
      a highly specific PERK inhibitor reduced the intracellular Ca2+ rise stimulated
      by the activation of acetylcholine, metabotropic glutamate and bradykinin-2
      receptors in primary cortical neurons. More specifically, acute PERK inhibition
      increased IP3 receptor mediated ER Ca2+ release, but decreased receptor-operated
      extracellular Ca2+ influx. Impaired Gq protein-coupled intracellular Ca2+ rise
      was also observed in genetic Perk knockout neurons. Taken together, our findings
      reveal a novel role of PERK in neurons, which is eIF2alpha-independent, and
      suggest that the impaired working memory in forebrain-specific Perk knockout mice
      may stem from altered Gq protein-coupled intracellular Ca2+ dynamics in cortical
      pyramidal neurons.

PMID- 27716401
TI  - Altered gut microbiota in female mice with persistent low body weights following
      removal of post-weaning chronic dietary restriction.
AB  - BACKGROUND: Nutritional interventions often fail to prevent growth failure in
      childhood and adolescent malnutrition and the mechanisms remain unclear. Recent
      studies revealed altered microbiota in malnourished children and anorexia
      nervosa. To facilitate mechanistic studies under physiologically relevant
      conditions, we established a mouse model of growth failure following chronic
      dietary restriction and examined microbiota in relation to age, diet, body
      weight, and anabolic treatment. METHODS: Four-week-old female BALB/c mice (n =
      12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain
      (LF). A subset of restricted mice was treated with an insulin-like growth factor
      1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and
      IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days
      69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S
      rRNA gene. Microbiota-host factor associations were analyzed by distance-based
      PERMANOVA and quantified by the coefficient of determination R2 for age, diet,
      and normalized body weight change (Deltabwt). Microbial taxa on day 120 were
      compared following fitting with an overdispersed Poisson regression model. The
      machine learning algorithm Random Forests was used to predict age based on the
      microbiota. RESULTS: On day 120, Deltabwt in AL, LF, LF-RF, and TLF-RF mice was
      52 +/- 3, -6 +/- 1*, 40 +/- 3*, and 46 +/- 2 % (*, P < 0.05 versus AL). Age and
      diet, but not Deltabwt, were associated with gut microbiota composition. Age
      explained a larger proportion of the microbiota variability than diet or
      Deltabwt. Random Forests predicted chronological age based on the microbiota and
      indicated microbiota immaturity in the LF mice before, but not after, refeeding.
      However, on day 120, the microbiota community structure of LF-RF mice was
      significantly different from that of both AL and LF mice. IGF1 mitigated the
      difference from the AL group. Refed groups had a higher abundance of
      Bacteroidetes and Proteobacteria and a lower abundance of Firmicutes than AL
      mice. CONCLUSIONS: Persistent growth failure can be induced by 97-day dietary
      restriction in young female mice and is associated with microbiota changes seen
      in lean mice and individuals and anorexia nervosa. IGF1 facilitates recovery of
      body weights and microbiota.

PMID- 27716402
TI  - Decatecholaminisation during sepsis.

PMID- 27716403
TI  - Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid
      through inhibition of urate transporters in the kidney.
AB  - BACKGROUND: Excess body burden of uric acid promotes gout. Diminished renal
      clearance of uric acid causes hyperuricemia in most patients with gout, and the
      renal urate transporter (URAT)1 is important for regulation of serum uric acid
      (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout
      therapies; however, their use is limited by drug-drug interactions and off-target
      toxicity, respectively. Here, we define the mechanism of action of lesinurad
      (Zurampic(r); RDEA594), a novel URAT1 inhibitor, recently approved in the USA and
      Europe for treatment of chronic gout. METHODS: sUA levels, fractional excretion
      of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad
      were measured in healthy volunteers treated with lesinurad. In addition,
      lesinurad, probenecid, and benzbromarone were compared in vitro for effects on
      urate transporters and the organic anion transporters (OAT)1 and OAT3, changes in
      mitochondrial membrane potential, and human peroxisome proliferator-activated
      receptor gamma (PPARgamma) activity. RESULTS: After 6 hours, a single 200-mg dose
      of lesinurad elevated FEUA 3.6-fold (p < 0.001) and reduced sUA levels by 33 % (p
      < 0.001). At concentrations achieved in the clinic, lesinurad inhibited activity
      of URAT1 and OAT4 in vitro, did not inhibit GLUT9, and had no effect on ABCG2.
      Lesinurad also showed a low risk for mitochondrial toxicity and PPARgamma
      induction compared to benzbromarone. Unlike probenecid, lesinurad did not inhibit
      OAT1 or OAT3 in the clinical setting. CONCLUSION: The pharmacodynamic effects and
      in vitro activity of lesinurad are consistent with inhibition of URAT1 and OAT4,
      major apical transporters for uric acid. Lesinurad also has a favorable
      selectivity and safety profile, consistent with an important role in sUA-lowering
      therapy for patients with gout.

PMID- 27716405
TI  - Noninvasive ventilation for avoidance of reintubation in patients with various
      cough strength.
AB  - BACKGROUND: Reintubation is associated with high mortality. Identification of
      methods to avoid reintubation is needed. The aim of this study was to assess
      whether prophylactic noninvasive ventilation (NIV) would benefit patients with
      various cough strengths. METHODS: We prospectively enrolled 356 patients who
      successfully passed a spontaneous breathing trial in a respiratory intensive care
      unit. Before extubation, cough peak flow was measured. After extubation,
      attending physicians determined whether the patients would receive prophylactic
      NIV or conventional oxygen treatment (control group). Patients were followed up
      to 90 days postextubation or death, whichever came first. RESULTS: The median
      value of cough peak flow was 70 L/minute. Among the patients with cough peak flow
      <=70 L/minute, 108 received NIV and 72 received conventional oxygen treatment. In
      this cohort, NIV reduced reintubation (9 % vs. 35 % at postextubation 72 h, p <
      0.01; and 24 % vs. 49 % at postextubation 7 days, p < 0.01) and postextubation 90
      day mortality (43 % vs. 61 %, p = 0.02) compared with the control group. Further,
      use of NIV was an independent protective factor for reintubation (OR = 0.19, p <
      0.01 at 72 h postextubation; and OR = 0.33, p < 0.01 at 7 days postextubation)
      and for death at 90 days postextubation (OR = 0.40, p = 0.02). Among patients
      with cough peak flow >70 L/minute, 71 received NIV and 105 received conventional
      oxygen treatment. In this cohort, NIV did not reduce reintubation (6 % vs. 6 % at
      72 h postextubation, p > 0.99; and 9 % vs. 9 % at 7 days postextubation, p >
      0.99) or postextubation 90-day mortality (21 % vs. 15 %, p = 0.32) compared with
      the control group. Further, use of NIV was not associated with reintubation or
      postextubation 90-day mortality. CONCLUSION: In a planned extubated population,
      prophylactic NIV benefited patients with weak cough but possibly not in patients
      with strong cough.

PMID- 27716406
TI  - Pseudomonas mendocina native valve infective endocarditis: a case report.
AB  - BACKGROUND: Gram-negative microorganisms are uncommon pathogens responsible for
      infective endocarditis. Pseudomonas mendocina, a Gram-negative water-borne and
      soil-borne bacterium, was first reported to cause human infection in 1992. Since
      then, it has rarely been reported as a human pathogen in the literature. We
      describe the first case of native valve infective endocarditis due to P.
      mendocina in the USA. CASE PRESENTATION: A 57-year-old white man presented with
      bilateral large leg ulcers, fever, and marked leukocytosis. His past medical
      history included gout and chronic alcohol use. P. mendocina was isolated from his
      blood cultures. A comprehensive review of P. mendocina infection in the
      literature was performed. A total of eight cases of P. mendocina infection were
      reported in the literature. More than two-thirds of the cases of P. mendocina
      septicemia were associated with native valve infective endocarditis. Thus, an
      echocardiogram was performed and demonstrated mitral valve endocarditis with mild
      mitral insufficiency. His leg wounds were debrided and were probably the source
      of P. mendocina bacteremia. Unlike Pseudomonas aeruginosa, P. mendocina is
      susceptible to third-generation cephalosporins. Our patient received a 6-week
      course of antimicrobial therapy with a favorable clinical outcome. CONCLUSIONS:
      Our reported case and literature review illuminates a rare bacterial cause of
      infective endocarditis secondary to P. mendocina pathogen. Native cardiac valves
      were affected in all reported cases of infective endocarditis, and a majority of
      affected heart valves were left-sided. The antibiotics active against P.
      mendocina are different from those that are active against P. aeruginosa, and
      they notably include third-generation cephalosporins. The outcome of all reported
      cases of P. mendocina was favorable and no mortality was described.

PMID- 27716404
TI  - Clinicopathological characteristics of patients with amyotrophic lateral
      sclerosis resulting in a totally locked-in state (communication Stage V).
AB  - In the present study, we performed a comprehensive analysis to clarify the
      clinicopathological characteristics of patients with amyotrophic lateral
      sclerosis (ALS) that had progressed to result in a totally locked-in state
      (communication Stage V), in which all voluntary movements are lost and
      communication is impossible. In 11 patients, six had phosphorylated TAR DNA
      binding protein 43 (pTDP-43)-immunoreactive (ir) neuronal cytoplasmic inclusions
      (NCI), two had fused in sarcoma (FUS)-ir NCI, and three had copper/zinc
      superoxide dismutase (SOD1)-ir NCI. The time from ALS onset to the need for
      tracheostomy invasive ventilation was less than 24 months in ten patients.
      Regardless of accumulated protein, all the patients showed common lesions in the
      pallido-nigro-luysian system, brainstem reticular formation, and cerebellar
      efferent system, in addition to motor neurons. In patients with pTDP-43-ir NCI,
      patients with NCI in the hippocampal dentate granule neurons (DG) showed a
      neuronal loss in the cerebral cortex, and patients without NCI in DG showed a
      preserved cerebral cortex. By contrast, in patients with FUS-ir NCI, patients
      with NCI in DG showed a preserved cerebral cortex and patients without NCI in DG
      showed marked cerebral degeneration. The cerebral cortex of patients with SOD1-ir
      NCI was preserved. Together, these findings suggest that lesions of the cerebrum
      are probably not necessary for progression to Stage V. In conclusion, patients
      with ALS that had progressed to result in communication Stage V showed rapidly
      progressed symptoms, and their common lesions could cause the manifestations of
      communication Stage V.

PMID- 27716407
TI  - An adaptive detection method for fetal chromosomal aneuploidy using cell-free DNA
      from 447 Korean women.
AB  - BACKGROUND: Noninvasive prenatal testing (NIPT) using massively parallel
      sequencing of cell-free DNA (cfDNA) is increasingly being used to predict fetal
      chromosomal abnormalities. However, concerns over erroneous predictions which
      occur while performing NIPT still exist in pregnant women at high risk for fetal
      aneuploidy. We performed the largest-scale clinical NIPT study in Korea to date
      to assess the risk of false negatives and false positives using next-generation
      sequencing. METHODS: A total of 447 pregnant women at high risk for fetal
      aneuploidy were enrolled at 12 hospitals in Korea. They underwent definitive
      diagnoses by full karyotyping by blind analysis and received aneuploidy screening
      at 11-22 weeks of gestation. Three steps were employed for cfDNA analyses. First,
      cfDNA was sequenced. Second, the effect of GC bias was corrected using
      normalization of samples as well as LOESS and linear regressions. Finally,
      statistical analysis was performed after selecting a set of reference samples
      optimally adapted to a test sample from the whole reference samples. We evaluated
      our approach by performing cfDNA testing to assess the risk of trisomies 13, 18,
      and 21 using the sets of extracted reference samples. RESULTS: The adaptive
      selection algorithm presented here was used to choose a more optimized reference
      sample, which was evaluated by the coefficient of variation (CV), demonstrated a
      lower CV and higher sensitivity than standard approaches. Our adaptive approach
      also showed that fetal aneuploidies could be detected correctly by clearly
      splitting the z scores obtained for positive and negative samples. CONCLUSIONS:
      We show that our adaptive reference selection algorithm for optimizing trisomy
      detection showed improved reliability and will further support practitioners in
      reducing both false negative and positive results.

PMID- 27716408
TI  - The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for
      Alzheimer's disease.
AB  - BACKGROUND: Synaptic degeneration is a central pathogenic event in Alzheimer's
      disease that occurs early during the course of disease and correlates with
      cognitive symptoms. The pre-synaptic vesicle protein synaptotagmin-1 appears to
      be essential for the maintenance of an intact synaptic transmission and cognitive
      function. Synaptotagmin-1 in cerebrospinal fluid is a candidate Alzheimer
      biomarker for synaptic dysfunction that also may correlate with cognitive
      decline. METHODS: In this study, a novel mass spectrometry-based assay for
      measurement of cerebrospinal fluid synaptotagmin-1 was developed, and was
      evaluated in two independent sample sets of patients and controls. Sample set I
      included cerebrospinal fluid samples from patients with dementia due to
      Alzheimer's disease (N = 17, age 52-86 years), patients with mild cognitive
      impairment due to Alzheimer's disease (N = 5, age 62-88 years), and controls (N =
      17, age 41-82 years). Sample set II included cerebrospinal fluid samples from
      patients with dementia due to Alzheimer's disease (N = 24, age 52-84 years),
      patients with mild cognitive impairment due to Alzheimer's disease (N = 18, age
      58-83 years), and controls (N = 36, age 43-80 years). RESULTS: The
      reproducibility of the novel method showed coefficients of variation of the
      measured synaptotagmin-1 peptide 215-223 (VPYSELGGK) and peptide 238-245
      (HDIIGEFK) of 14 % or below. In both investigated sample sets, the CSF levels of
      synaptotagmin-1 were significantly increased in patients with dementia due to
      Alzheimer's disease (P <= 0.0001) and in patients with mild cognitive impairment
      due to Alzheimer's disease (P < 0.001). In addition, in sample set I the
      synaptotagmin-1 level was significantly higher in patients with mild cognitive
      impairment due to Alzheimer's disease compared with patients with dementia due to
      Alzheimer's disease (P <= 0.05). CONCLUSIONS: Cerebrospinal fluid synaptotagmin-1
      is a promising biomarker to monitor synaptic dysfunction and degeneration in
      Alzheimer's disease that may be useful for clinical diagnosis, to monitor effect
      on synaptic integrity by novel drug candidates, and to explore pathophysiology
      directly in patients with Alzheimer's disease.

PMID- 27716409
TI  - A systematic review on the effectiveness of back protectors for motorcyclists.
AB  - BACKGROUND: Motorcyclists are a vulnerable road-user population who are
      overrepresented in traffic injuries. Utilisation of back protectors may be an
      effective preventive measure for spine injuries in motorcyclists. Since use of
      back protectors is increasing it is important that clinical evidence supports
      their use. The study aimed to investigate the current evidence on the ability of
      back protectors to reduce the rate of back injuries and patient mortality in
      motorcycle crashes. METHODS: A systematic literature search was conducted using
      various electronic databases. Systematic reviews, randomised controlled trials,
      controlled clinical trials, cohort studies, case series and case reports were
      included Opinion pieces and laboratory or biomechanical studies were excluded.
      Back protectors and spine protectors were included as the intervention; neck
      braces and speed humps were excluded. The target outcomes were any injuries to
      the back or death. Only English language studies were included. RESULTS: The
      search strategy yielded 185 studies. After excluding 183 papers by title and
      abstract and full-text evaluation, only two small cross-sectional studies were
      included. Foam inserts in motorcycle jackets and non-standard clothing may
      possibly be associated with higher risk of injuries, while hard shell and
      standard back protectors may possibly be associated with a reduced rate of back
      and spinal injury. CONCLUSION: This systematic review highlighted lack of
      appropriate evidence on efficacy of back protectors. Based on limited
      information, we are uncertain about the effects of back protectors on spinal
      injuries. Further research is required to substantiate the effects of back
      protectors on mortality and other injuries to the back.

PMID- 27716410
TI  - Seizure protein 6 and its homolog seizure 6-like protein are physiological
      substrates of BACE1 in neurons.
AB  - BACKGROUND: The protease BACE1 (beta-site APP cleaving enzyme) is a major drug
      target in Alzheimer's disease. However, BACE1 therapeutic inhibition may cause
      unwanted adverse effects due to its additional functions in the nervous system,
      such as in myelination and neuronal connectivity. Additionally, recent proteomic
      studies investigating BACE1 inhibition in cell lines and cultured murine neurons
      identified a wider range of neuronal membrane proteins as potential BACE1
      substrates, including seizure protein 6 (SEZ6) and its homolog SEZ6L. METHODS AND
      RESULTS: We generated antibodies against SEZ6 and SEZ6L and validated these
      proteins as BACE1 substrates in vitro and in vivo. Levels of the soluble, BACE1
      cleaved ectodomain of both proteins (sSEZ6, sSEZ6L) were strongly reduced upon
      BACE1 inhibition in primary neurons and also in vivo in brains of BACE1-deficient
      mice. BACE1 inhibition increased neuronal surface levels of SEZ6 and SEZ6L as
      shown by cell surface biotinylation, demonstrating that BACE1 controls surface
      expression of both proteins. Moreover, mass spectrometric analysis revealed that
      the BACE1 cleavage site in SEZ6 is located in close proximity to the membrane,
      similar to the corresponding cleavage site in SEZ6L. Finally, an improved method
      was developed for the proteomic analysis of murine cerebrospinal fluid (CSF) and
      was applied to CSF from BACE-deficient mice. Hereby, SEZ6 and SEZ6L were
      validated as BACE1 substrates in vivo by strongly reduced levels in the CSF of
      BACE1-deficient mice. CONCLUSIONS: This study demonstrates that SEZ6 and SEZ6L
      are physiological BACE1 substrates in the murine brain and suggests that sSEZ6
      and sSEZ6L levels in CSF are suitable markers to monitor BACE1 inhibition in
      mice.

PMID- 27716412
TI  - Killing filarial nematode parasites: role of treatment options and host immune
      response.
AB  - BACKGROUND: There is compelling evidence that not only do anti-filarials
      significantly reduce larval forms, but that host immune responses also contribute
      to the clearance of filarial parasites; however, the underlying mechanisms have
      not been fully elucidated. MAIN TEXT: Filarial infections caused by Wuchereria
      bancrofti and Brugia species (lymphatic filariasis) and Onchocerca volvulus
      (onchocerciasis) affect almost 200 million individuals worldwide and pose major
      public health challenges in endemic regions. Indeed, the collective disability
      adjusted life years for both infections is 3.3 million. Infections with these
      thread-like nematodes are chronic and, although most individuals develop a
      regulated state, a portion develop severe forms of pathology. Mass drug
      administration (MDA) programmes on endemic populations focus on reducing
      prevalence of people with microfilariae, the worm's offspring in the blood, to
      less than 1 %. Although this has been successful in some areas, studies show that
      MDA will be required for longer than initially conceived. CONCLUSION: This paper
      highlights the mode of action of the various antifilarial treatment strategies
      and role of host immune response.

PMID- 27716411
TI  - Genetic, histochemical and biochemical studies on goat TSE cases from Cyprus.
AB  - Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform
      encephalopathies (TSE's) affecting sheep and goats. Susceptibility of goats to
      scrapie is influenced by polymorphisms of the prion protein gene (PRNP) of the
      host. Five polymorphisms are associated with reduced susceptibility to TSE's. In
      the study presented here caprine samples from a scrapie eradication program on
      Cyprus were genotyped and further characterized using BioRad TeSeE rapid test,
      histological, immunohistochemical and biochemical methods. In total 42 goats from
      20 flocks were necropsied from which 25 goats showed a positive result in the
      rapid test, a spongiform encephalopathy and an accumulation of pathological prion
      protein (PrPSc) in the obex. PrPSc deposits were demonstrated in the placenta,
      peripheral nervous and lymphoreticular system. Two animals showed PrPSc
      accumulations in peripheral tissues only. By discriminatory immunoblots a scrapie
      infection could be confirmed for all cases. Nevertheless, slight deviations in
      the glycosylation pattern might indicate the presence of different scrapie
      strains. Furthermore scrapie samples from goats in the current study demonstrated
      less long term resistance to proteinase K than ovine or caprine BSE control
      samples. Reduced scrapie susceptibility according to the PRNP genotype was
      demonstrated (Fishers Exact test, p < 0.05) for the goats with at least one
      polymorphism (p = 0.023) at the six codons examined and in particular for those
      with polymorphisms at codon 146 (p = 0.016). This work characterizes scrapie in
      goats having implications for breeding and surveillance strategies.

PMID- 27716413
TI  - Pulmonary tumor diagnosed as an undifferentiated sarcoma with epithelioid
      features: a case report.
AB  - BACKGROUND: Pulmonary sarcomas are uncommon accounting for 0.5 % of all primary
      lung cancers. Undifferentiated sarcomas account for up to 20 % of soft tissue
      sarcomas. A lung tumor revealed to be an undifferentiated sarcoma with
      epithelioid features has never been reported in the literature. CASE
      PRESENTATION: A 61-year-old white Moroccan man presented with 2 months' history
      of hemoptysis and dyspnea. Chest computed tomography showed a cystic mass
      involving the lower field of his right lung evoking first a hydatid cyst.
      Abdominal computed tomography revealed bilateral adrenal nodules. Surgical
      resection of the lung mass was performed. On pathological examination, the tumor
      was cystic containing necrotic material. A histological diagnosis of
      undifferentiated sarcoma with epithelioid features was made. A positron emission
      tomography scan showed involvement of his pleura, left colon, adrenal glands,
      left thigh muscle, and leptomeninges. CONCLUSIONS: Undifferentiated sarcoma with
      epithelioid features is a rare malignant mesenchymal tumor. Clinical and
      radiological features are not specific. A differential diagnosis includes
      sarcomatoid carcinoma, malignant mesothelioma, melanoma, and other epithelioid
      sarcomas.

PMID- 27716414
TI  - Analyzing climate variations at multiple timescales can guide Zika virus response
      measures.
AB  - BACKGROUND: The emergence of Zika virus (ZIKV) in Latin America and the Caribbean
      in 2014-2016 occurred during a period of severe drought and unusually high
      temperatures, conditions that have been associated with the 2015-2016 El Nino
      event, and/or climate change; however, no quantitative assessment has been made
      to date. Analysis of related flaviviruses transmitted by the same vectors
      suggests that ZIKV dynamics are sensitive to climate seasonality and longer-term
      variability and trends. A better understanding of the climate conditions
      conducive to the 2014-2016 epidemic may permit the development of climate
      informed short and long-term strategies for ZIKV prevention and control. RESULTS:
      Using a novel timescale-decomposition methodology, we demonstrate that the
      extreme climate anomalies observed in most parts of South America during the
      current epidemic are not caused exclusively by El Nino or climate change, but by
      a combination of climate signals acting at multiple timescales. In Brazil, the
      dry conditions present in 2013-2015 are primarily explained by year-to-year
      variability superimposed on decadal variability, but with little contribution of
      long-term trends. In contrast, the warm temperatures of 2014-2015 resulted from
      the compound effect of climate change, decadal and year-to-year climate
      variability. CONCLUSIONS: ZIKV response strategies made in Brazil during the
      drought concurrent with the 2015-2016 El Nino event, may require revision in
      light of the likely return of rainfall associated with the borderline La Nina
      event expected in 2016-2017. Temperatures are likely to remain warm given the
      importance of long term and decadal scale climate signals.

PMID- 27716415
TI  - An evidence synthesis of the international knowledge base for new care models to
      inform and mobilise knowledge for multispecialty community providers (MCPs).
AB  - BACKGROUND: NHS England's Five Year Forward View (NHS England, Five Year Forward
      View, 2014) formally introduced a strategy for new models of care driven by
      simultaneous pressures to contain costs, improve care and deliver services closer
      to home through integrated models. This synthesis focuses on a multispecialty
      community provider (MCP) model. This new model of care seeks to overcome the
      limitations in current models of care, often based around single condition
      focused pathways, in contrast to patient-focused delivery (Royal College of
      General Practitioners, The 2022 GP: compendium of evidence, 2012) which offers
      greater continuity of care in recognition of complex needs and multimorbidity.
      METHODS: The synthesis, an innovative combination of best fit framework synthesis
      and realist synthesis, will develop a "blueprint" which articulates how and why
      MCP models work, to inform design of future iterations of the MCP model. A
      systematic search will be conducted to identify research and practice-derived
      evidence to achieve a balance that captures the historical legacy of MCP models
      but focuses on contemporary evidence. Sources will include bibliographic
      databases including MEDLINE, PreMEDLINE, CINAHL, Embase, HMIC and Cochrane
      Library; and grey literature sources. The Best Fit synthesis methodology will be
      combined with a synthesis following realist principles which are particularly
      suited to exploring what works, when, for whom and in what circumstances.
      DISCUSSION: The aim of this synthesis is to provide decision makers in health and
      social care with a practical evidence base relating to the multispecialty
      community provider (MCP) model of care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42016039552 .

PMID- 27716416
TI  - Human-biting activities of Anopheles species in south-central Ethiopia.
AB  - BACKGROUND: Indoor residual spraying (IRS) and long-lasting insecticidal nets
      (LLINs) are the key malaria vector control interventions in Ethiopia. The success
      of these interventions rely on their efficacy to repel or kill indoor feeding and
      resting mosquitoes. This study was undertaken to monitor human-biting patterns of
      Anopheles species in south-central Ethiopia. METHODS: Human-biting patterns of
      anophelines were monitored for 40 nights in three houses using human landing
      catches (HLC) both indoors and outdoors between July and November 2014, in Edo
      Kontola village, south-central Ethiopia. This time coincides with the major
      malaria transmission season in Ethiopia, which is usually between September and
      November. Adult mosquitoes were collected from 19:00 to 06:00 h and identified to
      species. Comparisons of HLC data were done using incidence rate ratio (IRR)
      calculated by negative binomial regression. The nocturnal biting activities of
      each Anopheles species was expressed as mean number of mosquitoes landing per
      person per hour. To assess malaria infections in Anopheles mosquitoes the
      presence of Plasmodium falciparum and P. vivax circumsporozoite proteins (CSP)
      were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Altogether
      3,408 adult female anophelines were collected, 2,610 (76.6 %) outdoors and 798
      (23.4 %) indoors. Anopheles zeimanni was the predominant species (66.5 %)
      followed by An. arabiensis (24.8 %), An. pharoensis (6.8 %) and An. funestus
      (s.l.) (1.8 %). The overall mean anopheline density was 3.3 times higher outdoors
      than indoors (65.3 vs 19.9/person/night, IRR: 3.3, 95 % CI: 1.1-5.1, P = 0.001).
      The mean density of An. zeimanni, An. pharoensis and An. funestus (s.l.)
      collected outdoors was significantly higher than indoors for each species (P <
      0.05). However, the mean An. arabiensis density outdoors was similar to that
      indoors (11.8 vs 9.4/person/night, IRR: 1.3, 95 % CI: 0.8-1.9, P = 0.335). The
      mean hourly human-biting density of An. arabiensis was greater outdoors than
      indoors and peaked between 21:00 and 22:00 h. However, An. arabiensis parous
      population showed high indoor man biting activities during bedtimes (22:00 to
      05:00 h) when the local people were indoor and potentially protected by IRS and
      LLINs. All mosquito samples tested for CSP antigen were found negative to malaria
      parasites. CONCLUSIONS: Results show much greater mosquito human-biting
      activities occurring outdoors than indoors and during early parts of the night,
      implying higher outdoor malaria transmission potential in the area. However, high
      bedtime (22:00 to 05:00 h) indoor biting activities of parous An. arabiensis
      suggest high potential intervention impact of IRS and LLINs on indoor malaria
      transmission.

PMID- 27716417
TI  - Importance of rare gene copy number alterations for personalized tumor
      characterization and survival analysis.
AB  - It has proven exceedingly difficult to ascertain rare copy number alterations
      (CNAs) that may have strong effects in individual tumors. We show that a
      regulatory network inferred from gene expression and gene copy number data of 768
      human cancer cell lines can be used to quantify the impact of patient-specific
      CNAs on survival signature genes. A focused analysis of tumors from six tissues
      reveals that rare patient-specific gene CNAs often have stronger effects on
      signature genes than frequent gene CNAs. Further comparison to a related network
      based approach shows that the integration of indirectly acting gene CNAs
      significantly improves the survival analysis.

PMID- 27716418
TI  - Shotgun proteomic analysis of Yersinia ruckeri strains under normal and iron
      limited conditions.
AB  - Yersinia ruckeri is the causative agent of enteric redmouth disease of fish that
      causes significant economic losses, particularly in salmonids. Bacterial
      pathogens differentially express proteins in the host during the infection
      process, and under certain environmental conditions. Iron is an essential
      nutrient for many cellular processes and is involved in host sensing and
      virulence regulation in many bacteria. Little is known about proteomics
      expression of Y. ruckeri in response to iron-limited conditions. Here, we present
      whole cell protein identification and quantification for two motile and two non
      motile strains of Y. ruckeri cultured in vitro under iron-sufficient and iron
      limited conditions, using a shotgun proteomic approach. Label-free, gel-free
      quantification was performed using a nanoLC-ESI and high resolution mass
      spectrometry. SWATH technology was used to distinguish between different strains
      and their responses to iron limitation. Sixty-one differentially expressed
      proteins were identified in four Y. ruckeri strains. These proteins were involved
      in processes including iron ion capture and transport, and enzymatic metabolism.
      The proteins were confirmed to be differentially expressed at the transcriptional
      level using quantitative real time PCR. Our study provides the first detailed
      proteome analysis of Y. ruckeri strains, which contributes to our understanding
      of virulence mechanisms of Y. ruckeri, and informs development of novel control
      methods for enteric redmouth disease.

PMID- 27716419
TI  - The impact of mild induced hypothermia on the rate of transfusion and the
      mortality in severely injured patients: a retrospective multi-centre study.
AB  - BACKGROUND: Although under discussion, induced hypothermia (IH) is an established
      therapy for patients with cardiac arrest or traumatic brain injuries. The
      influences on coagulopathy and bleeding tendency in severely injured patients
      (SIP) with concomitant traumatic brain injury are most widely unclear. Therefore,
      the aim of this study was to quantify the effect of mild IH in SIP with
      concomitant severe traumatic brain injuries on transfusion rate and mortality.
      METHODS: In this retrospective multi-centre study, SIP from three European level
      1 trauma centres with an ISS >=16 between 2009 and 2011 were included. At
      hospital A, patients qualified for IH with age <=70 years and a severe head
      injury with an abbreviated injury scale (AISHead) of >=3. IH was defined as
      target core body temperature of 35  degrees C. Hypothermic patients were matched
      with two patients, one from hospital B and one from hospital C using age and
      AISHead. The effect of IH on the transfusion rate, complications and mortality
      was quantified with 95 % confidence intervals (CI). Patients not treated with IH
      in hospital A and those from hospital B and C, who were not matched, were used to
      adjust the CI for the effect of inter-hospital therapy protocol differences.
      RESULTS: Mean age of patients in the IH-group (n = 43) was 35.7 years, mean ISS
      30 points and sex distribution showed 83.7 % male. Mean age of matched patients
      in the normotherm-group (n = 86) was 36.7 years, mean ISS 33 points and there
      were 75.6 % males. For the hypothermic patients, we pointed out an estimate of
      mean difference for the number of transfused units of packed red blood cells as
      well as for mortality which does not indicate a decrease in the benefit gained by
      hypothermia. It is suggested that hypothermic patients tend to a higher rate of
      lung failure and thromboembolisms. CONCLUSION: Though tending to an increased
      rate of complications, there is no evidence for a difference in both; rate of
      transfusion and mortality in SIP. Mild IH as an option for severe head injuries
      seems as well-being practicable in the presence of multiple severe injuries.
      Further, clinical studies regarding the side effects are necessary.

PMID- 27716420
TI  - Household perceptions and subjective valuations of indoor residual spraying
      programmes to control malaria in northern Uganda.
AB  - BACKGROUND: Insecticide-based tools remain critical for controlling vector-borne
      diseases in Uganda. Securing public support from targeted populations for such
      tools is an important component in sustaining their long-run effectiveness. Yet
      little quantitative evidence is available on the perceived benefits and costs of
      vector control programmes among targeted households. METHODS: A survey was
      administered to a clustered random sample of 612 households in Gulu and Oyam
      districts of northern Uganda during a period of very high malaria transmission
      and following a pilot indoor residual spray (IRS) programme. A discrete choice
      experiment was conducted within the survey, in which respondents indicated their
      preferences for different IRS programmes relative to money compensation in a
      series of experimentally controlled, hypothetical choice sets. The data were
      analysed using conditional logit regression models to estimate respondents'
      willingness to accept (WTA) some amount of money compensation in lieu of foregone
      malaria risk reductions. Latent class models were used to analyse whether
      respondent characteristics predicted WTA. RESULTS: Average WTA is estimated at
      $8.94 annually for a 10 % reduction in malaria risk, and additional co-benefits
      of IRS were estimated to be worth on average $54-$56 (depending on insecticide
      type) per round of IRS. Significant heterogeneity is observed: Four in five
      household heads in northern Uganda have high valuations for IRS programmes, while
      the remaining 20 % experience costly side effects of IRS (valued at between $2
      and $3 per round). Statistically significant predictors of belonging to the high
      value group include respondent gender, mean age of household members,
      participation in previous IRS, basic knowledge of mosquito reproduction, and the
      number of mosquito nets owned. Proxies for household income and wealth are not
      found to be statistically significant predictors of WTA. CONCLUSIONS: This study
      suggests that the majority of people in areas of high malaria transmission like
      northern Uganda place a high value on vector control programmes using IRS.
      However, there is significant heterogeneity in terms of the perceived side
      effects (positive and negative). This has implications for sustaining public
      support for these programmes in the long-term.

PMID- 27716421
TI  - A spatial analysis of human Schistosoma japonicum infections in Hubei, China,
      during 2009-2014.
AB  - BACKGROUND: The province of Hubei is located in the middle of China, near the
      middle and lower reaches of the River Yangtze, and is an area where
      schistosomiasis is endemic. It is challenging to control this disease in this
      environment, and it would be useful to identify clusters of infection and
      transmission, as well as their distributions during recent years. Therefore, this
      study aimed to analyze the spatial distribution of schistosomiasis in Hubei, in
      order to facilitate the effective control and elimination of this disease.
      METHODS: We collected schistosomiasis surveillance data from all endemic counties
      in Hubei during 2009-2014. A geographical information system (ArcGIS, version
      10.1) was used to link the counties' geographical data with the epidemiological
      data, and the spatial scanning method (FleXScan v3.1.2) was used to identify
      spatial clusters of human infections with Schistosoma japonicum. RESULTS: In
      Hubei, patients who exhibited stool test results that were positive for S.
      japonicum accounted for > 50 % of all cases in China during 2009-2014. However,
      each endemic county in Hubei exhibited a declining trend in the number of human
      S. japonicum infections during the study period. The ArcGIS analyses revealed
      that the middle reaches of the River Yangtze were highly endemic for S. japonicum
      infections. Spatial scan analyses revealed the following infection clusters: two
      clusters in ten counties during 2009, two clusters in nine counties during 2010,
      three clusters in 12 counties during 2011, two clusters in 12 counties during
      both 2012 and 2013 and two clusters in ten counties during 2014. Most of the
      cluster regions were located in the lake and marshland regions along the basins
      of the River Yangtze. CONCLUSION: We successfully identified schistosomiasis
      clusters at the county level in Hubei during 2009-2014, and our results revealed
      that the clusters were typically located in lake and marshland regions. These
      data may be useful for controlling and eliminating schistosomiasis in other high
      risk areas.

PMID- 27716423
TI  - Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence
      and association with peripheral neuropathy.
AB  - BACKGROUND: The association between long-term metformin use and low vitamin B12
      levels has been proven. However, the prevalence estimates of metformin-induced
      vitamin B12 deficiency showed considerable variation among the studies. The
      potential of the deficiency to cause or worsen peripheral neuropathy in type-2
      diabetes mellitus (T2DM) patients has been investigated with conflicting results.
      The aim of the study was to investigate: 1) the prevalence of vitamin B12
      deficiency in T2DM patients on metformin; 2) the association between vitamin B12
      and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in
      these patients. METHODS: In this cross-sectional study, consecutive metformin
      treated T2DM patients attending diabetes clinics of two public hospitals in South
      Africa were approached for participation. Participation included measuring
      vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total
      Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency
      (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores
      >6 were considered to have peripheral neuropathy. The relationship between
      vitamin B12 and peripheral neuropathy was investigated when the two variables
      were in the binary and continuous forms. Multiple logistic regression was used to
      determine risk factors for vitamin B12 deficiency. RESULTS: Among 121
      participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no
      difference in presence of neuropathy between those with normal and deficient
      vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6
      scores were not correlated (Spearman's rho =0.056, P = 0.54). HbA1c (mmol/mol)
      (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI:
      0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin
      B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR =
      1.96, 95 % CI: 0.99 to 3.88, P = 0.053). CONCLUSIONS: Close to third of metformin
      treated T2DM patients had vitamin B12 deficiency. The deficiency was not
      associated with peripheral neuropathy. Black race was a protective factor for
      vitamin B12 deficiency.

PMID- 27716422
TI  - A statistical analysis plan for the efficiency and safety of Chinese herbal
      medicine used concurrently with topical therapy for psoriasis vulgaris.
AB  - BACKGROUND: Psoriasis vulgaris (PV) has been causing increasing concern due to
      its highly prevalent, harmful and therapy-resistant characteristics. The YXBCM01
      (Chinese herbal medicine) for PV trial evaluates the effects of YXBCM01 on
      relapse rate in patients suffering from PV. As an update to the published design
      and method for the trial, this paper presents the statistical plan for the main
      publication to avoid the risk of outcome reporting bias, selective reporting, and
      data-driven results. METHODS/DESIGN: This trial is a multicenter, randomized,
      double-blind, placebo-controlled, parallel-group clinical trial. A total of 600
      PV patients (300 in each group) will be randomized to one of two arms:
      participants in the experimental group will receive the YXBCM01 granule 5.5 g
      twice daily for 12 weeks. Placebo granules are given to patients in the control
      group at a dose of 5.5 g twice daily for 12 weeks. The sequential topical therapy
      is administrated simultaneously to all eligible patients by using calcipotriol
      betamethasone ointment once daily (a treatment area of up to 30 % body surface
      area (BSA), fingertip unit is recommended) in the first 4 weeks (maximum of 100 g
      weekly), followed by calcipotriol betamethasone ointment once daily for the
      remaining 8 weeks (maximum of 100 g weekly). The primary outcome measure is
      relapse rate in the treatment period and follow-up period. The secondary outcome
      measures include time to relapse, time to onset, rebound rate, cumulative
      consumption of topical medicine, visual analog scale (VAS), BSA, the Dermatology
      Life Quality Index (DLQI) and the Medical Outcomes Study (MOS) 36-item short form
      health survey (SF-36). CONCLUSIONS: Application of this statistical analysis plan
      to the YXBCM01 for PV trial will facilitate unbiased evaluation of these
      important clinical data. This study will provide evidence regarding the value of
      YXBCM01 as an intervention for PV patients. TRIAL REGISTRATION: Chinese Clinical
      Trial Registry: ChiCTR-TRC-13003233 , registered on 26 May 2013.

PMID- 27716424
TI  - Anti-inflammatory effects of Salvia plebeia R. Br extract in vitro and in
      ovalbumin-induced mouse model.
AB  - BACKGROUND: Asthma is an increasing global health problem, and novel strategies
      to prevent or ameliorate the condition are needed. Here, the effects of 80 %
      ethanol extracts of Salvia plebeia R. Br. (SE) on an induced inflammatory
      response were investigated. RESULTS: Salvia plebeia R. Br. inhibited production
      of pro-inflammatory cytokines, such as TNF-alpha and IL-6, as well as nitric
      oxide (NO) in LPS-stimulated RAW 264.7 cells. NO and pro-inflammatory cytokine
      production was suppressed more effectively by SE of the aerial parts (SE-A) than
      of the roots (SE-R) of S. plebeia. In BEAS-2B cells, both SE-A and SE-R inhibited
      the increase in production of the inflammatory cytokines IL-6 and IL-8. We also
      investigated the anti-asthmatic effects of SE in an ovalbumin (OVA)-induced
      BALB/c mouse model. SE-A treatment significantly reduced the number of airway
      eosinophils, IL-4 and IL-13 levels, mucus production, and inflammatory
      infiltration, as compared with the corresponding levels in the untreated, OVA
      induced mice, and had similar effects to dexamethasone. CONCLUSIONS: Salvia
      plebeia ethanol extract ameliorated the induced inflammatory response in RAW
      264.7 and BEAS-2B cells, with more effective inhibition noted for SE-A than for
      SE-R. SE-A treatment was effective in improving the histopathological changes in
      the lungs of asthma model mice via modulation of eosinophils and Th2 cytokines.
      These results suggest that SE-A can be considered as a therapeutic agent that can
      potentially relieve asthma.

PMID- 27716425
TI  - Flank pseudohernia following posterior rib fracture: a case report.
AB  - BACKGROUND: A pseudohernia is an abdominal wall bulge that may be mistaken for a
      hernia but that lacks the disruption of the abdominal wall that characterizes a
      hernia. Thus, the natural history and treatment of this condition differ from
      those of a hernia. This is the first report of a pseudohernia due to cough
      associated rib fracture. CASE PRESENTATION: A case of pseudohernia due to
      fractures of the 10th and 11th ribs in a 68-year-old white woman is presented.
      The patient suffered from a major coughing episode 1 year prior to her
      presentation, after which she noted a progressively enlarging bulge in her left
      flank. Computed tomography demonstrated a bulge in the abdominal wall containing
      bowel and spleen but with all muscle and fascial layers intact; in addition,
      lateral 10th rib and posterior 11th rib fractures were noted. CONCLUSIONS: As
      there was no defect in muscle or fascia, we diagnosed a pseudohernia, likely due
      to a denervation injury from the fractured ribs. Symptomatic treatment was
      recommended, including wearing a corset and referral to a pain management clinic.
      Symptomatic treatment is thought to be the mainstay of therapy for pseudohernias,
      as surgical intervention is unlikely to be of benefit.

PMID- 27716426
TI  - Mean platelet volume in children with hepatitis A.
AB  - BACKGROUND: Mean platelet volume (MPV), which is commonly used as a measure of
      platelet size, indicates the rate of platelet production and platelet activation.
      We aimed to evaluate the mean platelet volume in children with hepatitis A.
      METHODS: In this retrospective case-controlled study, the study population
      consisted of 62 children with hepatitis A and 62 healthy control subjects.
      RESULTS: MPV values, aspartate transaminase (AST), and alanine transaminase (ALT)
      levels on admission were significantly increased in patients with hepatitis A
      when compared to controls whereas white blood cell (WBC) counts were
      significantly lower. Two weeks after admission, the MPV values showed a
      significant decrease from 9.47 +/- 1.62 to 8.84 +/- 1.48 fL in patients with
      hepatitis A, but these values were still significantly higher than the controls.
      There was a significant difference in terms of MPV, WBC, AST, and ALT values
      between the controls and the patient group 2 weeks after admission. CONCLUSIONS:
      This study is the first to evaluate the MPV levels in children with hepatitis A.
      MPV values were found to be increased in children hospitalized with hepatitis A.

PMID- 27716428
TI  - Successful use of rivaroxaban in postoperative deep vein thrombosis of the lower
      limb following instability with warfarin: a case report.
AB  - BACKGROUND: Evidence from clinical trials shows rivaroxaban to be effective for
      the treatment of deep vein thrombosis. Switching to rivaroxaban following failure
      of indirect anticoagulants in deep vein thrombosis has not been demonstrated in a
      real-life setting. CASE PRESENTATION: A 43-year-old white woman was switched from
      warfarin to rivaroxaban for the treatment of thrombosis of her right common
      femoral vein after saphenectomy. The reason for the switch was due to the
      instability of anti-coagulation therapy with vitamin K antagonists over a period
      of 3 months during which she did not reach the "therapeutic range" of prothrombin
      time-international normalized ratio. The ineffectiveness of the conventional oral
      anticoagulant was confirmed by persistence of moderate-high values of fibrin D
      dimers (780 ng/ml) and by residual vein thrombosis at an ultrasound examination.
      Objectively, her right leg appeared to be still edematous and warm and pain was
      elicited by deep palpation. Rivaroxaban was administered after warfarin
      discontinuation (prothrombin time-international normalized ratio = 1.43) at a
      dosage of 15 mg every 12 hours for 3 weeks, followed by 20 mg once daily for 3
      months. After this period, her objective symptoms significantly improved, with
      reduction of edema of her lower limb and pain relief. Her fibrin D dimer values
      returned to normal (210 ng/ml). An ultrasound showed recanalization of the
      obstructed venous segment. CONCLUSIONS: In this case report, a switch to
      rivaroxaban from warfarin was shown to be effective and safe for the treatment of
      postoperative deep vein thrombosis, whereas standard oral anticoagulation
      therapy, which required dose adjustments over a period of 3 months, was not able
      to stabilize the therapeutic range of prothrombin time-international normalized
      ratio nor improve our patient's outcome.

PMID- 27716427
TI  - A functional variant of TLR10 modifies the activity of NFkB and may help predict
      a worse prognosis in patients with rheumatoid arthritis.
AB  - BACKGROUND: Toll-like receptor (TLR) family members are key players in
      inflammation. TLR10 has been poorly studied in chronic inflammatory disorders,
      and its clinical relevance in rheumatoid arthritis (RA) is as yet unknown. We
      aimed at identifying TLR10 variants within all coding regions of the gene in
      patients with RA as well as studying their functional and clinical significance.
      METHODS: TLR10 gene variants were studied by performing sequencing of 66 patients
      with RA and 30 control subjects. A selected variant, I473T, was then analyzed in
      1654 patients and 1702 healthy control subjects. The capacity of this TLR10
      variant to modify the transcriptional activity of nuclear factor kappa-light
      chain-enhancer of activated B cells (NFkB) was determined by using a luciferase
      reporter assay and analyzing the expression of NFkB target genes by quantitative
      polymerase chain reaction. Differences between groups were analyzed by using the
      Mann-Whitney U test and the unpaired two-tailed Student's t test. RESULTS: We
      detected ten missense variants in the TLR10 gene and focused on the I473T
      substitution based on allele frequencies and the predicted functional impact.
      I473T variant is not associated with susceptibility to RA, but it significantly
      correlates with erosive disease in patients seropositive for antibodies to
      citrullinated protein antigens (p = 0.017 in the total cohort and p = 0.0049 in
      female patients) and with a lower response to infliximab treatment as measured by
      the change in Disease Activity Score in 28 joints (p = 0.012) and by the European
      League Against Rheumatism criteria (p = 0.049). Functional studies showed that
      TLR10 reduced activation of the NFkB inflammatory pathway in hematopoietic cells,
      whereas the I473T variant lacked this inhibitory capacity. Consistently, after
      exposure to infliximab, cells expressing the I437T variant showed higher NFkB
      activity than cells carrying wild-type TLR10. CONCLUSIONS: A TLR10 allelic
      variant, I473T, has impaired NFkB inhibitory activity and is highly associated
      with disease severity and low response to infliximab in patients with RA.

PMID- 27716429
TI  - Serosurveillance of viral pathogens circulating in West Africa.
AB  - BACKGROUND: Sub-Saharan Africa is home to a variety of pathogens, but disease
      surveillance and the healthcare infrastructure necessary for proper management
      and control are severely limited. Lassa virus, the cause of Lassa fever, a severe
      hemorrhagic fever in humans is endemic in West Africa. In Sierra Leone at the
      Kenema Government Hospital Lassa Diagnostic Laboratory, up to 70 % of acute
      patient samples suspected of Lassa fever test negative for Lassa virus infection.
      This large amount of acute undiagnosed febrile illness can be attributed in part
      to an array of hemorrhagic fever and arthropod-borne viruses causing disease that
      goes undetected and untreated. METHODS: To better define the nature and extent of
      viral pathogens infecting the Sierra Leonean population, we developed a
      multiplexed MAGPIX(r) assay to detect IgG antibodies against Lassa, Ebola,
      Marburg, Rift Valley fever, and Crimean-Congo hemorrhagic fever viruses as well
      as pan-assays for flaviviruses and alphaviruses. This assay was used to survey
      675 human serum samples submitted to the Lassa Diagnostic Laboratory between 2007
      and 2014. RESULTS: In the study population, 50.2 % were positive for Lassa virus,
      5.2 % for Ebola virus, 10.7 % for Marburg virus, 1.8 % for Rift Valley fever
      virus, 2.0 % for Crimean-Congo hemorrhagic fever virus, 52.9 % for flaviviruses
      and 55.8 % for alphaviruses. CONCLUSIONS: These data exemplify the importance of
      disease surveillance and differential diagnosis for viral diseases in Sierra
      Leone. We demonstrate the endemic nature of some of these viral pathogens in the
      region and suggest that unrecognized outbreaks of viral infection have occurred.

PMID- 27716430
TI  - A specific anti-citrullinated protein antibody profile identifies a group of
      rheumatoid arthritis patients with a toll-like receptor 4-mediated disease.
AB  - BACKGROUND: Increased expression of toll-like receptor 4 (TLR4) and its
      endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In
      this study, we evaluated how these TLR4 ligands may drive pathogenic processes
      and whether the fine profiling of anti-citrullinated protein antibodies (ACPA)
      based on their target specificity might provide a simple means to predict
      therapeutic benefit when neutralizing TLR4 in this disease. METHODS: The capacity
      of RA synovial fluids (RASF) to stimulate cytokine production in monocytes from
      patients with RA was analyzed by ELISA. The presence of TLR4 activators in RASF
      was determined by measuring the levels of ACPA, ACPA subtypes with reactivity to
      specific citrullinated peptides and other TLR4 ligands. Neutralization of TLR4
      signaling was investigated using NI-0101, a therapeutic antibody that targets
      TLR4. RESULTS: RASF exhibited a heterogeneous capacity to induce production of
      proinflammatory cytokines by monocytes isolated from patients with RA. Such
      cytokine responses were significantly modified by TLR4 blockade achieved using NI
      0101. The analysis of the content of RASF and matched sera demonstrated that ACPA
      fine specificities in patient samples predict cellular response to anti-TLR4
      exposure in vitro. CONCLUSION: TLR4 represents a possible therapeutic target in
      RA. Our study demonstrates that TLR4 inhibition in an ex vivo model of RA
      pathogenesis can significantly modulate cytokine release and does so in specific
      subgroups of RA patient-derived samples. It also suggests that ACPA fine
      profiling has the potential to identify RA patients with a predominantly TLR4
      driven pathotype that could be used to predict preferential response to TLR4
      antagonism.

PMID- 27716431
TI  - Tor1a+/- mice develop dystonia-like movements via a striatal dopaminergic
      dysregulation triggered by peripheral nerve injury.
AB  - Isolated generalized dystonia is a central motor network disorder characterized
      by twisted movements or postures. The most frequent genetic cause is a GAG
      deletion in the Tor1a (DYT1) gene encoding torsinA with a reduced penetrance of
      30-40 % suggesting additional genetic or environmental modifiers. Development of
      dystonia-like movements after a standardized peripheral nerve crush lesion in
      wild type (wt) and Tor1a+/- mice, that express 50 % torsinA only, was assessed by
      scoring of hindlimb movements during tail suspension, by rotarod testing and by
      computer-assisted gait analysis. Western blot analysis was performed for dopamine
      transporter (DAT), D1 and D2 receptors from striatal and quantitative RT-PCR
      analysis for DAT from midbrain dissections. Autoradiography was used to assess
      the functional DAT binding in striatum. Striatal dopamine and its metabolites
      were analyzed by high performance liquid chromatography. After nerve crush
      injury, we found abnormal posturing in the lesioned hindlimb of both mutant and
      wt mice indicating the profound influence of the nerve lesion (15x vs. 12x
      relative to control) resembling human peripheral pseudodystonia. In mutant mice
      the phenotypic abnormalities were increased by about 40 % (p < 0.05). This was
      accompanied by complex alterations of striatal dopamine homeostasis.
      Pharmacological blockade of dopamine synthesis reduced severity of dystonia-like
      movements, whereas treatment with L-Dopa aggravated these but only in mutant mice
      suggesting a DYT1 related central component relevant to the development of
      abnormal involuntary movements. Our findings suggest that upon peripheral nerve
      injury reduced torsinA concentration and environmental stressors may act in
      concert in causing the central motor network dysfunction of DYT1 dystonia.

PMID- 27716432
TI  - Transmission of methicillin-resistant Staphylococcus aureus in long-term care
      facilities and their related healthcare networks.
AB  - BACKGROUND: Long-term care facilities (LTCF) are potential reservoirs for
      methicillin-resistant Staphylococcus aureus (MRSA), control of which may reduce
      MRSA transmission and infection elsewhere in the healthcare system. Whole-genome
      sequencing (WGS) has been used successfully to understand MRSA epidemiology and
      transmission in hospitals and has the potential to identify transmission between
      these and LTCF. METHODS: Two prospective observational studies of MRSA carriage
      were conducted in LTCF in England and Ireland. MRSA isolates were whole-genome
      sequenced and analyzed using established methods. Genomic data were available for
      MRSA isolated in the local healthcare systems (isolates submitted by hospitals
      and general practitioners). RESULTS: We sequenced a total of 181 MRSA isolates
      from the two study sites. The majority of MRSA were multilocus sequence type
      (ST)22. WGS identified one likely transmission event between residents in the
      English LTCF and three putative transmission events in the Irish LTCF. WGS also
      identified closely related isolates present in colonized Irish residents and
      their immediate environment. Based on phylogenetic reconstruction, closely
      related MRSA clades were identified between the LTCF and their healthcare
      referral network, together with putative MRSA acquisition by LTCF residents
      during hospital admission. CONCLUSIONS: These data confirm that MRSA is
      transmitted between residents of LTCF and is both acquired and transmitted to
      others in referral hospitals and beyond. Our data present compelling evidence for
      the importance of environmental contamination in MRSA transmission, reinforcing
      the importance of environmental cleaning. The use of WGS in this study highlights
      the need to consider infection control in hospitals and community healthcare
      facilities as a continuum.

PMID- 27716433
TI  - Utilization of screening mammography in older women according to comorbidity and
      age: protocol for a systematic review.
AB  - BACKGROUND: Approximately half of new invasive breast cancer cases diagnosed each
      year in the United States occur among women aged 65 years and older. The
      increasing life expectancy coupled with the attendant rise in breast cancer
      incidence and elimination of out-of-pocket expenses for screening mammography as
      a result of the Affordable Care Act could lead to higher utilization rates of
      screening mammography. Although research indicates that life expectancy should be
      a strong consideration when making screening decisions among older women, the
      extent to which screening mammography utilization is tailored to comorbidity and
      life expectancy is not well established. METHODS/DESIGN: To identify relevant
      studies, a systematic search of the literature will be conducted using PubMed and
      EMBASE between January 1, 1991, and March 1, 2016. Additional studies will be
      found through citation review or by contacting experts in the field. The
      inclusion criteria will be any study design comprised of women aged 65 and older,
      assessing women's comorbidity, functional impairments, and/or health status, and
      reporting outcome measures that addressed mammography utilization within the last
      1-5 years. For each study, two authors will independently abstract data regarding
      study eligibility and outcomes to determine relevance. Quantitative results will
      be extracted from text and tables, choosing preferably those adjusted for
      important confounders. DISCUSSION: The review will provide evidence on the impact
      of comorbidity, functional limitations, and health status on screening
      mammography utilization in older women and inform decision aids in this area.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016032661.

PMID- 27716435
TI  - Lessons on malaria control in the ethnic minority regions in Northern Myanmar
      along the China border, 2007-2014.
AB  - BACKGROUND: For many countries where malaria is endemic, the burden of malaria is
      high in border regions. In ethnic minority areas along the Myanmar-China border,
      residents have poor access to medical care for diagnosis and treatment, and there
      have been many malaria outbreaks in such areas. Since 2007, with the support of
      the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), a malaria
      control project was introduced to reduce the malaria burden in several ethnic
      minority regions. METHODS: A malaria control network was established during the
      period from 2007 to 2014. Multiple malaria interventions, including diagnosis,
      treatment, distribution of LLINs and health education, were conducted to improve
      the accessibility and quality of malaria control services for local residents.
      Annual cross-sectional surveys were conducted to evaluate intervention coverage
      and indicators of malaria transmission. RESULTS: In ethnic minority regions where
      a malaria control network was established, both the annual malaria incidence
      (19.1 per thousand per year, in 2009; 8.7, in 2014) and malaria prevalence (13.6
      % in 2008; 0.43 % in 2014) decreased dramatically during the past 5-6 years. A
      total of 851 393 febrile patients were detected, 202 598 malaria cases (including
      confirmed cases and suspected cases) were treated, and 759 574 LLINs were
      delivered to populations at risk. Of households in 2012, 73.9 % had at least one
      ITNs/LLINs (vs. 28.3 %, in 2008), and 50.7 % of children less than 5 years and
      50.3 % of pregnant women slept under LLINs the night prior to their visit.
      Additionally, malaria knowledge was improved in 68.4 % of residents. CONCLUSION:
      There has been great success in improving malaria control in these regions from
      2007 to 2014. Malaria burdens have decreased, especially in KOK and WA. The
      continued maintenance of sustainable malaria control networks in these regions
      may be a long-term process, due to regional conflicts and the lack of funds,
      technology, and health workers. Furthermore, information and scientific support
      from the international community should be offered to these ethnic minority
      regions to uphold recent achievements.

PMID- 27716436
TI  - Are ethical norms and current policies still relevant in face of the recent mass
      terror events?
AB  - The widespread utilization of social media in recent terror attacks in major
      European cities should raise a "red flag" for the emergency medical response
      teams. The question arises as to the impact of social media during terror events
      on the healthcare system. Information was published well before any emergency
      authority received a distress call or was requested to respond. Photos published
      at early stages of the attacks, through social media were uncensored, presenting
      identifiable pictures of victims. Technological advancements of recent years
      decrease and remove barriers that enable the public to use them as they see fit.
      These attacks raise ethical considerations for the patients and their rights as
      they were outsourced from the medical community, into the hands of the public.
      The healthcare system should leverage social media and its advantages in
      designing response to terror, but this requires a re-evaluation and introspection
      into the current emergency response models.

PMID- 27716434
TI  - Oestrogen-induced angiogenesis and implantation contribute to the development of
      parasitic myomas after laparoscopic morcellation.
AB  - BACKGROUND: Iatrogenic parasitic myomas (PMs), caused by intra-corporeal power
      morcellation during laparoscopy is gradually increasing. However, the
      pathogenesis and medical treatment of PMs remain largely unelucidated. METHODS:
      Laparoscopically-induced PM xenografted mouse model was conducted by xenografting
      human uterine myoma fragments into the abdominal cavity of SCID mice and hormonal
      manipulation was performed using this mouse model to demonstrate the role of
      oestrogen in the development of implanted PMs. Immunohistochemistry of oestrogen
      receptor alpha (ERalpha), progesterone receptor (PR), vimentin, vascular
      endothelial growth factor (VEGF), microvessel density (MVD) and Ki-67 index was
      performed and compared. RESULTS: In the patient with PMs, ERalpha, PR,
      angiogenesis and proliferative property expression were upregulated in PM lesions
      compared to uterine myomas. In the laparoscopically-induced PM mouse model,
      implanted myomas had more steroid receptor expressions, angiogenesis and
      proliferative property compared with pre-xenografted or non-implanted myoma.
      Depletion of oestrogen in the ovariectomized (OVX) mice decreased
      laparoscopically-induced PM implantations. In comparison, the implantations of
      PMs were increased with additional E2 supplement. Hormonal manipulation in the PM
      mouse model, including AI, GnRHa and SERM groups, were compared and AI
      significantly decreased the implantations, steroid receptor, angiogenesis, cell
      density, and proliferative index of PMs compared with control group. Furthermore,
      GnRHa significantly decreased VEGF and MVD expressions compared with control
      group. CONCLUSIONS: These data highlight the crucial role of oestrogen in the
      development of laparoscopically-induced PMs and suggest that hormone manipulation
      may be a potential therapeutic agent. TRIAL REGISTRATION: This protocol was
      approved by the Human and Animal Institutional Review Board of Taipei Veterans
      General Hospital ( VGHIRB No 2014-10-002C on Nov. 17th, 2014; IACUC 2014-119 on
      Aug. 22nd, 2014).

PMID- 27716437
TI  - Effects of developmental exposure to silver in ionic and nanoparticle form: A
      study in rats.
AB  - BACKGROUND: Evaluations of silver in both nanoparticle (Ag-NPs) and ionic forms
      indicate some adverse effects on living organisms, but little is known about
      their potential for developmental toxicity. In this study, developmental toxicity
      of Ag-NPs (from 0.2 to 20 mg/kg/day) and ionic Ag (AgNO3, 20 mg Ag/kg/day) were
      investigated in rats. METHODS: Animals were dosed by gavage from gestation day 7 
      20. The day after parturition, dams and pups were sacrificed and Ag level
      assessed in several maternal and pup organs. In addition, hepatotoxicity and
      oxidative stress parameters and histopathology were evaluated. RESULTS: No
      treatment related effects were found for gestational parameters including
      pregnancy length, maternal weight gain, implantations, birth weight and litter
      size at any dose level of Ag-NPs. Maternal weight gain was lower in dams
      receiving AgNO3 compared to the other groups, suggesting that the ionic form may
      exert a higher degree of toxicity compared to the NP form. Tissue contents of Ag
      were higher in all treated groups compared to control dams and pups, indicating
      transfer of Ag across the placenta. The findings furthermore suggest that Ag may
      induce oxidative stress in dams and their offspring, although significant
      induction was only observed after dosing with AgNO3. Histopathological
      examination of brain tissue revealed a high incidence of hippocampal sclerosis in
      dams treated with nanoparticle as well as ionic Ag. CONCLUSION: The difference in
      offspring deposition patterns between ionic and NP Ag and the observations in dam
      brain tissue, requires scrutiny, and, if corroborated, indicate that ionic and NP
      forms maybe need separate risk assessments and that the hazard ratings of silver
      in both ionic and nanoparticle forms should be increased, respectively. TRIAL
      REGISTRATION: Not applicable. Developmental Toxicity of Ag-NPs.

PMID- 27716438
TI  - The impact of co-infections on fish: a review.
AB  - Co-infections are very common in nature and occur when hosts are infected by two
      or more different pathogens either by simultaneous or secondary infections so
      that two or more infectious agents are active together in the same host. Co
      infections have a fundamental effect and can alter the course and the severity of
      different fish diseases. However, co-infection effect has still received limited
      scrutiny in aquatic animals like fish and available data on this subject is still
      scarce. The susceptibility of fish to different pathogens could be changed during
      mixed infections causing the appearance of sudden fish outbreaks. In this review,
      we focus on the synergistic and antagonistic interactions occurring during co
      infections by homologous or heterologous pathogens. We present a concise summary
      about the present knowledge regarding co-infections in fish. More research is
      needed to better understand the immune response of fish during mixed infections
      as these could have an important impact on the development of new strategies for
      disease control programs and vaccination in fish.

PMID- 27716439
TI  - Effect of timing of hip extension assistance during loaded walking with a soft
      exosuit.
AB  - BACKGROUND: Recent advances in wearable robotic devices have demonstrated the
      ability to reduce the metabolic cost of walking by assisting the ankle joint. To
      achieve greater gains in the future it will be important to determine optimal
      actuation parameters and explore the effect of assisting other joints. The aim of
      the present work is to investigate how the timing of hip extension assistance
      affects the positive mechanical power delivered by an exosuit and its effect on
      biological joint power and metabolic cost during loaded walking. In this study,
      we evaluated 4 different hip assistive profiles with different actuation timings:
      early-start-early-peak (ESEP), early-start-late-peak (ESLP), late-start-early
      peak (LSEP), late-start-late-peak (LSLP). METHODS: Eight healthy participants
      walked on a treadmill at a constant speed of 1.5 m . s-1 while carrying a 23 kg
      backpack load. We tested five different conditions: four with the assistive
      profiles described above and one unpowered condition where no assistance was
      provided. We evaluated participants' lower limb kinetics, kinematics, metabolic
      cost and muscle activation. RESULTS: The variation of timing in the hip extension
      assistance resulted in a different amount of mechanical power delivered to the
      wearer across conditions; with the ESLP condition providing a significantly
      higher amount of positive mechanical power (0.219 +/- 0.006 W . kg-1) with
      respect to the other powered conditions. Biological joint power was significantly
      reduced at the hip (ESEP and ESLP) and at the knee (ESEP, ESLP and LSEP) with
      respect to the unpowered condition. Further, all assistive profiles significantly
      reduced the metabolic cost of walking compared to the unpowered condition by 5.7
      +/- 1.5 %, 8.5 +/- 0.9 %, 6.3 +/- 1.4 % and 7.1 +/- 1.9 % (mean +/- SE for ESEP,
      ESLP, LSEP, LSLP, respectively). CONCLUSIONS: The highest positive mechanical
      power delivered by the soft exosuit was reported in the ESLP condition, which
      showed also a significant reduction in both biological hip and knee joint power.
      Further, the ESLP condition had the highest average metabolic reduction among the
      powered conditions. Future work on autonomous hip exoskeletons may incorporate
      these considerations when designing effective control strategies.

PMID- 27716441
TI  - Shock wave-induced ATP release from osteosarcoma U2OS cells promotes cellular
      uptake and cytotoxicity of methotrexate.
AB  - BACKGROUND: Osteosarcoma is the most prevalent primary malignant bone tumor, but
      treatment is difficult and prognosis remains poor. Recently, large-dose
      chemotherapy has been shown to improve outcome but this approach can cause many
      side effects. Minimizing the dose of chemotherapeutic drugs and optimizing their
      curative effects is a current goal in the management of osteosarcoma patients.
      METHODS: In our study, trypan blue dye exclusion assay was performed to
      investigate the optimal conditions for the sensitization of osteosarcoma U2OS
      cells. Cellular uptake of the fluorophores Lucifer Yellow CH dilithium salt and
      Calcein was measured by qualitative and quantitative methods. Human MTX ELISA Kit
      and MTT assay were used to assess the outcome for osteosarcoma U2OS cells in the
      present of shock wave and methotrexate. To explore the mechanism, P2X7 receptor
      in U2OS cells was detected by immunofluorescence and the extracellular ATP levels
      was detected by ATP assay kit. All data were analyzed using SPSS17.0 statistical
      software. Comparisons were made with t test between two groups. RESULTS:
      Treatment of human osteosarcoma U2OS cells with up to 450 shock wave pulses at 7
      kV or up to 200 shock wave pulses at 14 kV had little effect on cell viability.
      However, this shock wave treatment significantly promoted the uptake of Calcein
      and Lucifer Yellow CH by osteosarcoma U2OS cells. Importantly, shock wave
      treatment also significantly enhanced the uptake of the chemotherapy drug
      methotrexate and increased the rate of methotrexate-induced apoptosis. We found
      that shock wave treatment increased the extracellular concentration of ATP and
      that KN62, an inhibitor of P2X7 receptor reduced the capacity methotrexate
      induced apoptosis. CONCLUSIONS: Our results suggest that shock wave treatment
      promotes methotrexate-induced apoptosis by altering cell membrane permeability in
      a P2X7 receptor-dependent manner. Shock wave treatment may thus represent a
      possible adjuvant therapy for osteosarcoma.

PMID- 27716440
TI  - A field tool for prediction of body fat in Sri Lankan women: skinfold thickness
      equation.
AB  - BACKGROUND: Valid skinfold thickness (SFT) equations for the prediction of body
      fat are currently unavailable for South Asian women and would be a potentially
      robust field tool. Our aim was to assess the validity of existing SFT equations
      against deuterium (2H2O) dilution and, if invalid, to develop and validate an SFT
      equation for % fat mass (%FM) in Sri Lankan women. METHODS: H2O dilution was used
      with Fourier transform infrared (FTIR) spectroscopy as the criterion method for
      the assessment of %FM in urban Sri Lankan women (30-45 years). This data was used
      to assess the validity of available SFT equations and to generate and validate a
      new SFT equation for the prediction of %FM against the criterion method. Women (n
      = 164) were divided into validation and cross-validation groups for the
      development and validation of the new equation. The level of agreement between
      the %FM calculated by the final derived prediction equation and the %FM obtained
      by 2H2O dilution was assessed using Pearson's correlation coefficient (R) and
      Bland Altman plots. Student's t test was used to assess over- or underestimation,
      and significance was set at p < 0.05. RESULTS: Existing equations significantly
      (p < 0.001) underestimated %FM compared with the 2H2O dilution method. The final
      equation obtained was %FM = 19.621 + (0.237*weight) + (0.259*triceps). When
      compared with 2H2O dilution, %FM by the equation was not significantly different.
      There was a significant (p < 0.001) correlation between %FM by the reference
      method and %FM by the equation. The limit of agreement by Bland Altman plot was
      narrow with a small mean positive bias. CONCLUSIONS: Existing SFT equations were
      not applicable to this population. The new equation derived was valid. We report
      a new SFT equation to predict %FM in women of South Asian ancestry suitable for
      field use.

PMID- 27716442
TI  - Treatment of unilateral spatial neglect after stroke using transcranial direct
      current stimulation (ELETRON trial): study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Unilateral spatial neglect (USN) is characterized by the inability to
      report or respond to people or objects that are presented in the spatial
      hemisphere that is contralateral to the lesioned hemisphere of the brain. USN has
      been associated with poor functional outcomes and long stays in hospitals and
      rehabilitation centers. Noninvasive brain stimulation, such as transcranial
      direct current stimulation (tDCS), has been used in people who have been affected
      by USN after stroke. The effects of such treatment could provide new insights for
      health professionals and policy-makers. The aim of this study will be to evaluate
      the effectiveness and safety of tDCS for USN after stroke. METHODS: A prospective
      randomized controlled trial with two parallel groups will be conducted, which
      will aim to recruit 60 patients with USN after ischemic or hemorrhagic stroke.
      Participants will be randomly placed into the following four treatment groups:
      (1) anodal tDCS over the right parietal lobe (n = 15), (2) cathodal tDCS over the
      left parietal lobe (n = 15), (3) a sham group of anodal tDCS over the right
      parietal lobe (n = 15), and (4) a sham group of cathodal tDCS over the left
      parietal lobe (n = 15). Blinded assessors will conduct two baseline assessments
      and one post-intervention assessment. The primary outcome measure will be the
      level of USN as assessed by the conventional Behavioral Inattention Tasks and the
      Catherine Bergego Scale. Secondary measures will include neurological capacity
      (based on the Scandinavian Stroke Scale), functional capacity (based on the
      Functional Independence Measure and Modified Rankin Scale), autonomy (based on
      the Barthel Index), and quality of life (based on the EuroQol-5D). Group
      allocation will be concealed, and all analyses will be based on an intention-to
      treat principle. DISCUSSION: This study will explore the effects of more than 15
      sessions of tDCS on the level of USN, functional capacity, autonomy, and quality
      of life in patients with USN after stroke. This proposed study has the potential
      to identify a new, evidence-based intervention that can enhance perception and
      independent living in patients with USN after stroke. TRIAL REGISTRATION: REBEC -
      RBR-78jvzx , registered on 13 March 2016.

PMID- 27716443
TI  - A discrete cluster of urinary biomarkers discriminates between active systemic
      lupus erythematosus patients with and without glomerulonephritis.
AB  - BACKGROUND: Management of lupus nephritis (LN) would be greatly aided by the
      discovery of biomarkers that accurately reflect changes in disease activity.
      Here, we used a proteomics approach to identify potential urinary biomarkers
      associated with LN. METHODS: Urine was obtained from 60 LN patients with paired
      renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using
      Luminex, 128 analytes were quantified and normalized to urinary creatinine
      levels. Data were analyzed by linear modeling and non-parametric statistics, with
      corrections for multiple comparisons. A second cohort of 33 active LN, 16 active
      non-LN, and 30 remission LN SLE patients was used to validate the results.
      RESULTS: Forty-four analytes were identified that were significantly increased in
      active LN as compared to active non-LN. This included a number of unique proteins
      (e.g., TIMP-1, PAI-1, PF4, vWF, and IL-15) as well as known candidate LN
      biomarkers (e.g., adiponectin, sVCAM-1, and IL-6), that differed markedly (>4
      fold) between active LN and non-LN, all of which were confirmed in the validation
      cohort and normalized in remission LN patients. These proteins demonstrated an
      enhanced ability to discriminate between active LN and non-LN patients over
      several previously reported biomarkers. Ten proteins were found to significantly
      correlate with the activity score on renal biopsy, eight of which strongly
      discriminated between active proliferative and non-proliferative/chronic renal
      lesions. CONCLUSIONS: A number of promising urinary biomarkers that correlate
      with the presence of active renal disease and/or renal biopsy changes were
      identified and appear to outperform many of the existing proposed biomarkers.

PMID- 27716444
TI  - Survival after heart transplantation for non-metastatic primary cardiac sarcoma.
AB  - BACKGROUND: Heart transplantation is an uncommon treatment for unresectable and
      non-metastatic primary cardiac sarcomas, and the role of it is unclear. This
      study aims to offer a survival analysis of it. METHODS: This study consists of 6
      patients from our institution and 40 patients identified in a literature search
      who underwent heart transplantation for non-metastatic primary cardiac sarcomas.
      Seven patients with unresectable cardiac angiosarcoma who received palliative
      therapies at our institution were included for comparison. All the
      clinicopathologic data were collected, retrospectively reviewed and statistically
      analyzed. RESULTS: Among the 46 patients receiving heart transplantation for
      primary cardiac sarcomas, the overall median survival was 16 months (2-112
      months). The most common histologic type receiving heart transplantation was
      angiosarcoma. Its median survival time after heart transplantation (n = 14) was
      much less than that of other histologic types (n = 31) (9 vs 36 months; P =
      0.002), which means it was not different from the median survival of 8 months for
      patients (n = 7) receiving palliative therapies (P = 0.768). The patients with
      grade 2 cardiac sarcomas (n = 5) survived much longer after heart
      transplantations than patients with grade 3 tumors (n = 15) (mean survival: 85 vs
      18 months; P = 0.006). Neoadjuvant or adjuvant chemotherapy didn't provide
      survival benefits after heart transplantation. CONCLUSIONS: Cardiac angiosarcoma
      seems to be not the proper indication of heart transplantation. The role of heart
      transplantation in other histologic subtypes still remains undefined. Lower grade
      and less aggressive histologic subtypes benefit more from heart transplantation.

PMID- 27716445
TI  - Suppression of vagal cardiac modulation by blue light in healthy subjects.
AB  - BACKGROUND: In the contemporary life environments, our body is increasingly
      exposed to various sources of colored light, which may affect our physiological
      functions as non-image-forming effects. We examined the impacts of colored lights
      on the autonomic functions by the analysis of heart rate variability (HRV).
      METHODS: A lighting device consisting of four organic light-emitting diode (OLED)
      modules (55 * 55 mm2) with adjustable red-green-blue color was secured 24 cm
      above the eyes of subject lying supine in a light-shielded laboratory. Following
      a 15-min supine rest, electrocardiogram and respiration were measured
      continuously during 3-min darkness, 6-min colored OLED illumination, and 3-min
      darkness under paced breathing (15 breath/min). The measurements were repeated at
      a 45-min interval for red, green, and blue lights with melanopsin-stimulating
      photon flux density (MSPFD) of 0.00, 0.10, and 0.20 MUmol/m2/s, respectively, in
      12 healthy subjects (23 +/- 2 years, two females). Additionally, the effects of
      blue lights with 0.20, 0.10, and 0.04 MUmol/m2/s MSPFD were examined in four
      healthy subjects (25-39 years, two females). HRV was analyzed for low-frequency
      (LF, 0.04-0.15 Hz) and high-frequency (HF, 0.20-0.30 Hz) power and LF-to-HF ratio
      (LF/HF). RESULTS: Compared to darkness before lighting, HF power decreased (P <
      0.001) and LF/HF increased (P = 0.024) during lighting on average of all color
      lights, whereas HF power showed a greater decrease with blue light than with red
      and green lights (P < 0.05 for both). The decrease in HF power lasted even during
      darkness after lighting (P < 0.001). HF power decreased with blue light with 0.20
      MUmol/m2/s MSPFD (P < 0.001) but not with that with 0.10 or 0.04 MUmol/m2/s (P =
      0.1 and 0.9, respectively). CONCLUSIONS: Vagal cardiac modulation is suppressed
      by OLED blue light in healthy subjects most likely through melanopsin-dependent
      non-image-forming effect.

PMID- 27716446
TI  - Gait training assisted by multi-channel functional electrical stimulation early
      after stroke: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Many stroke survivors suffer from paresis of lower limb muscles,
      resulting in compensatory gait patterns characterised by asymmetries in spatial
      and temporal parameters and reduced walking capacity. Functional electrical
      stimulation has been used to improve walking capacity, but evidence is mostly
      limited to the orthotic effects of peroneal functional electrical stimulation in
      the chronic phase after stroke. The aim of this study is to investigate the
      therapeutic effects of up to 10 weeks of multi-channel functional electrical
      stimulation (MFES)-assisted gait training on the restoration of spatiotemporal
      gait symmetry and walking capacity in subacute stroke patients. METHODS: In a
      proof-of-principle study with a randomised controlled design, 40 adult patients
      with walking deficits who are admitted for inpatient rehabilitation within 31
      days since the onset of stroke are randomised to either MFES-assisted gait
      training or conventional gait training. Gait training is delivered in 30-minute
      sessions each workday for up to 10 weeks. The step length symmetry ratio is the
      primary outcome. Blinded assessors conduct outcome assessments at baseline, every
      2 weeks during the intervention period, immediately post intervention and at 3
      month follow-up. DISCUSSION: This study aims to provide preliminary evidence for
      the feasibility and effectiveness of MFES-assisted gait rehabilitation early
      after stroke. Results will inform the design of a larger multi-centre trial.
      TRIAL REGISTRATION: This trial is registered at the Netherlands Trial Register
      (number NTR4762 , registered 28 August 2014).

PMID- 27716447
TI  - Dramatic reduction of mortality in pneumococcal meningitis.
AB  - BACKGROUND: Acute bacterial meningitis is still a life threatening disease.
      METHODS: We performed a retrospective observational study on the clinical
      characteristics of consecutively admitted patients with acute pneumococcal
      meningitis in a single tertiary care center in central Europe (from 2003 until
      2015). Data were compared with a previously published historical group of 87
      patients treated for pneumococcal meningitis at the same hospital (from 1984
      until 2002). RESULTS: Fifty-five consecutive patients with microbiologically
      proven pneumococcal meningitis were included. Most striking, mortality was down
      to 5.5 %, which was significantly lower than in the historical group where 24.1 %
      of the patients did not survive. Intracranial complications during the course of
      the disease were common and affected half of the patients. Unlike in the historic
      group, most of the intracranial complications (except ischemic stroke) were no
      longer associated with a low Glasgow Outcome Score at discharge. CONCLUSION: The
      drastic reduction of mortality proves there have been important advances in the
      treatment of pneumococcal meningitis. Nevertheless, the fact that only 44.2 % of
      survivors had a full recovery indicates that the search for new adjunctive
      treatment options must be ongoing.

PMID- 27716448
TI  - The complement system is activated in synovial fluid from subjects with knee
      injury and from patients with osteoarthritis.
AB  - BACKGROUND: The complement system is suggested to be involved in the pathogenesis
      of osteoarthritis (OA), and proinflammatory cytokines may play a role in OA
      development by inducing proteases. The association between complement factors,
      cytokines and OA has not been investigated. The aim of the present study was to
      explore the involvement of the complement system after knee trauma and in OA.
      METHODS: C4d, C3bBbP and soluble terminal complement complex (sTCC) resulting
      from complement activation were immunoassayed in synovial fluid from subjects
      with healthy knees (reference), OA, rheumatoid arthritis (RA; positive control),
      pyrophosphate arthritis (PPA; positive control) and knee injury; other biomarkers
      were previously assessed. Magnetic resonance imaging was used to assess joint
      injuries. RESULTS: Compared with levels in the reference group, the median
      concentrations of C4d, C3bBbP and sTCC in the OA, RA, PPA and knee injury groups
      were 2- to 34-fold increased (p < 0.001 to p = 0.044). For the knee injury group,
      the median concentrations of C4d, C3bBbP and sTCC were 5- to 12-fold increased (p
      < 0.001) at the day of injury; after 3-12 weeks, C3bBbP and sTCC concentrations
      were similar to reference levels; and C4d was still increased several years after
      injury. In the 0-12 weeks period after injury, the concentrations of C4d, C3bBbP
      and sTCC correlated positively with levels of interleukin (IL)-1beta, IL-6 and
      tumour necrosis factor alpha (r s range 0.232-0.547); none of the measured
      complement factors correlated with proteolytic fragments of aggrecan or cartilage
      oligomeric matrix protein. Knees with osteochondral fracture, with or without
      disrupted cortical bone, had higher concentrations of C4d (p = 0.014, p = 0.004)
      and sTCC (p = 0.004, p < 0.001) compared with knees without fractures.
      CONCLUSIONS: The complement system is activated in OA and after knee injury.
      Following knee injury, this activation is instant and associated with
      inflammation as well as with the presence of osteochondral fractures.

PMID- 27716449
TI  - Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in
      partially resistant C57Bl/6 mice.
AB  - BACKGROUND: We have previously demonstrated that intranasal vaccination of highly
      susceptible BALB/c mice with whole Leishmania amazonensis antigens (LaAg) leads
      to protection against murine cutaneous leishmaniasis. Here, we evaluate the
      response of partially resistant C57BL/6 mice to vaccination as a more
      representative experimental model of human cutaneous leishmaniasis. METHODS:
      C57BL/6 mice from different animal facilities were infected with L. amazonensis
      (Josefa strain) to establish the profile of infection. Intranasal vaccination was
      performed before the infection challenge with two doses of 10 MUg of LaAg alone
      or associated with the adjuvant ADDAVAX(r) by instillation in the nostrils. The
      lesion progression was measured with a dial caliper and the parasite load by
      limited dilution assay in the acute and chronic phases of infection. Cytokines
      were quantified by ELISA in the homogenates of infected footpads. RESULTS:
      C57BL/6 mice from different animal facilities presented the same L. amazonensis
      infection profile, displaying a progressive acute phase followed by a controlled
      chronic phase. Parasites cultured in M199 and Schneider's media were equally
      infective. Intranasal vaccination with LaAg led to milder acute and chronic
      phases of the disease. The mechanism of protection was associated with increased
      production of IFN-gamma in the infected tissue as measured in the acute phase.
      Association with the ADDAVAX(r) adjuvant did not improve the efficacy of
      intranasal LaAg vaccination. Rather, ADDAVAX(r) reduced vaccination efficacy.
      CONCLUSION: This study demonstrates that the efficacy of adjuvant-free intranasal
      vaccination with LaAg is extendable to the more resistant C57Bl/6 mouse model of
      infection with L. amazonensis, and is thus not exclusive to the susceptible
      BALB/c model. These results imply that mucosal immunomodulation by LaAg leads to
      peripheral protection irrespective of the genetic background of the host.

PMID- 27716450
TI  - Picodroplet partitioned whole genome amplification of low biomass samples
      preserves genomic diversity for metagenomic analysis.
AB  - BACKGROUND: Whole genome amplification (WGA) is a challenging, key step in
      metagenomic studies of samples containing minute amounts of DNA, such as samples
      from low biomass environments. It is well known that multiple displacement
      amplification (MDA), the most commonly used WGA method for microbial samples,
      skews the genomic representation in the sample. We have combined MDA with droplet
      microfluidics to perform the reaction in a homogeneous emulsion. Each droplet in
      this emulsion can be considered an individual reaction chamber, allowing
      partitioning of the MDA reaction into millions of parallel reactions with only
      one or very few template molecules per droplet. RESULTS: As a proof-of-concept,
      we amplified genomic DNA from a synthetic metagenome by MDA either in one bulk
      reaction or in emulsion and found that after sequencing, the species distribution
      was better preserved and the coverage depth was more evenly distributed across
      the genomes when the MDA reaction had been performed in emulsion. CONCLUSIONS:
      Partitioning MDA reactions into millions of reactions by droplet microfluidics is
      a straightforward way to improve the uniformity of MDA reactions for amplifying
      complex samples with limited amounts of DNA.

PMID- 27716451
TI  - Surgical treatment of a broken neuroplasty catheter in the epidural space: a case
      report.
AB  - BACKGROUND: Percutaneous epidural neuroplasty with a Racz catheter is widely used
      to treat radicular pain caused by spinal stenosis or a herniated intervertebral
      disc. The breakage or shearing of an epidural catheter, particularly a
      percutaneous epidural neuroplasty catheter, is reported as a rare complication.
      There has been a controversy over whether surgical removal of a shorn epidural
      catheter is needed. Until now, only three cases related to sheared Racz
      neuroplasty catheters have been reported. We report a case of a neuroplasty
      catheter which completely broke when it was inserted into the epidural space, and
      compressed root symptoms were exacerbated by the broken catheter. CASE
      PRESENTATION: A 68-year-old Asian man with leg pain and lower back pain caused by
      lumbar vertebral body 4 to lumbar vertebral body 5 intervertebral disc herniation
      and stenosis underwent percutaneous epidural neuroplasty. During the procedure,
      the epidural neuroplasty catheter was trapped in the left foraminal portion and
      broke. Our patient complained of left-side leg pain and numbness. Surgery
      performed to remove the broken catheter led to complete resolution of his leg
      pain and numbness. CONCLUSIONS: We report a rare case of catheter breakage
      occurring during epidural neuroplasty. We suggest surgical removal because the
      implanted catheter can aggravate a patient's symptoms and lead to the development
      of neurologic deficits due to infection, fibrosis, or mechanical neural
      irritation.

PMID- 27716452
TI  - Comparison of computed tomography features between follicular neoplasm and
      nodular hyperplasia.
AB  - BACKGROUND: To date, appropriate management for Bethesda IV thyroid nodules is
      controversial, and no specific features of follicular neoplasm and nodular
      hyperplasia on ultrasonography, computed tomography (CT), or other imaging
      modalities have been reported. This study aimed to compare CT features of
      follicular neoplasm and nodular hyperplasia and to determine the specific CT
      features that could be used to distinguish follicular neoplasm from nodular
      hyperplasia. METHODS: In 122 patients who underwent preoperative CT of the neck
      and thyroid surgery, 59 follicular neoplasms and 65 nodular hyperplasias were
      included. In each case, non-enhanced and contrast-enhanced CT images were
      obtained, and a single radiologist retrospectively analyzed CT images, including
      degree and pattern of attenuation, nodular configuration, margin, shape, pattern
      of calcification, degree and pattern of nodular enhancement, and CT halo sign. A
      univariate and multivariate logistic regression analyses were used to evaluate
      the predictive power of each variable and CT features with a high predictive
      power, respectively. RESULTS: According to the univariate analysis, iso
      attenuation, intraglandular configuration, smooth margin, ovoid shape, decreased
      enhancement, and absence of CT halo sign were more frequently observed in nodular
      hyperplasia (p < 0.05), whereas low attenuation, expansile configuration,
      lobulated margin, taller-than-wide shape, increased enhancement, and presence of
      computed tomography halo sign were more frequently observed in follicular
      neoplasm (p < 0.05). Multivariate analysis revealed significant differences in
      configuration (OR: 2.73, 1.13-6.57), degree of enhancement (OR: 2.14, 1.21-3.78),
      and presence of CT halo sign (OR: 7.97, 2.74-23.37) between follicular neoplasm
      and nodular hyperplasia (p < 0.05). CONCLUSIONS: Neck CT may be helpful for
      distinguishing follicular neoplasm from nodular hyperplasia. TRIAL REGISTRATION:
      Rretrospectively registered.

PMID- 27716453
TI  - Editorial.

PMID- 27716455
TI  - Editorial - A missing vas deferens: practical implications for urologists
      performing vasectomies and managing infertile men.

PMID- 27716454
TI  - Editorial - The case for excision and primary anastomotic urethroplasty for
      bulbar urethral stricture.

PMID- 27716456
TI  - Difference of opinion - Radical prostatectomy in metastatic prostate cancer: is
      there enough evidence? | Opinion: Yes.

PMID- 27716457
TI  - Difference of opinion - Radical prostatectomy in metastatic prostate cancer: is
      there enough evidence? | Opinion: No.

PMID- 27716458
TI  - One year in review 2016: pathogenesis of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic
      synovial inflammation leading to joint destruction and bone erosions. Although
      the pathogenic mechanisms underlying the disease are not fully elucidated, it is
      known that genetic susceptibility and environmental factors trigger an abnormal
      autoimmune response. Potentially, any organ and tissue could be affected by RA
      and the increased cardiovascular (CV) risk represents the major complication
      responsible for a worse prognosis. In this setting, the shared pathogenic
      mechanisms between RA pathogenesis and accelerated atherosclerosis further
      strengthen the rationale for a treat-to-target strategy with synthetic and
      biologic disease modifying anti-rheumatic drugs. The aim of this review is to
      provide the novel insights, regarding the pathogenesis of RA, published over the
      last year.

PMID- 27716459
TI  - Study of the bone behavior around a neck preserving short stem implant: bone
      densitometric analysis over a span of two years.
AB  - PURPOSE: Study the bone mineral density (BMD) changes and the remodelling process
      after implantation of a neck preserving short stem implant over a period of two
      years. METHODS: Using specific patients' selection criterion, a prospective study
      was done including 26 patients. All were operated upon by a single surgeon using
      the MiniHipTM, (Corin, Cirencester, UK). Mean age was 42.5 years. Clinical and
      radiological evaluation was done. Periprosthetic bone density was measured by
      DEXA. First scan was obtained within 10 days after surgery and served as a
      baseline for comparison. RESULTS: The mean pre-operative Harris Hip score of 37.8
      increased to 95.1 points two years post-operatively. BMD in the overall
      periprosthetic area showed a significant reduction during the first three months.
      Restoration to the original levels was reached in all zones except the most
      proximal zones at one year. A net increase was detected (+3%) after two years.
      CONCLUSION: The neck preserving MiniHip short stem implant has proven to be a
      bone-friendly design. Significant bone remodeling process continues after the
      first year. Although bone resorption in the greater trochanteric region is still
      a problem, however, it has proven that the BMD in all the other periprosthetic
      regions including the calcar and the lesser trochanteric regions, are subjected
      to bone formation process over a period of two years.

PMID- 27716460
TI  - Minimal important difference after hand surgery: a prospective assessment for
      DASH, MHQ, and SF-12.
AB  - INTRODUCTION: Minimal important difference (MID) score is an important measure
      for surgical clinical research and impacts on treatment decisions. Our approach
      considered patient satisfaction as the relevant anchor criteria. The aims of this
      study were: determine after surgery MID for three relevant questionnaires:
      Disabilities of the Arm, Shoulder and Hand (DASH), Michigan Hand Questionnaire
      (MHQ), and Short Form 12 (SF-12); and assess the correlation between these scores
      and patient reported satisfaction. METHODS: Adult patients where surgery was
      indicated for any hand/wrist conditions. Study was conducted in a teaching
      hospital, Sao Paulo, Brazil. Participants responded to DASH, SF-12, MHQ, and a
      Likert satisfaction scale before and three months after a procedure. Satisfaction
      was considered as the anchor for determining MID after a procedure. The
      correlation between satisfaction and the instruments were measured. Two
      statistical approaches were utilized for determining MIDs and were used for
      consistency and generalizability purposes. For MID determination, receiver
      operating curves were utilized and MID cut-offs were followed by sensitivity and
      specificity measures. RESULTS: Fifty patients were included with no follow-up
      losses. MID for DASH was 18.8 and 15.4. MID for MHQ was 14.7 for both approaches.
      Data from SF-12 was not reliable after statistical analyses and demonstrated poor
      correlation with patient satisfaction. MID for DASH and MHQ were found and
      demonstrated larger standards than literature-reported patients when surgery was
      not the main intervention. DASH and MHQ had moderate correlation with patient
      reported satisfaction. SF-12 MID was not reliable and had poor correlation to
      patient satisfaction. These data suggests that ambulatory hand surgery patients
      may have greater expectations regarding improvement than other patients.

PMID- 27716461
TI  - CT scan evaluation of glenoid bone and pectoralis major tendon: interest in
      shoulder prosthesis.
AB  - INTRODUCTION: The shoulder arthroplasty brings satisfaction to patients in terms
      of quality of life and indolence. However whether anatomic implant or reverse, it
      does not escape from the loosening of the glenoid component. Moreover, optimal
      implantation is required to ensure the functional outcome without shortening of
      the arm. The purpose of this study is obtain CT scan evaluation of the glenoid
      bone stock in order to optimize glenoid component implantation and obtain a
      reference to determine optimal humeral component placement in case of humeral
      proximal fracture. MATERIALS AND METHODS: Between 2010 and 2011 we have analyzed
      200 intact shoulder's CT. We measured maximal and minimal width in the transverse
      plane of the glenoid, the distance from the pectoralis major (PM) tendon to the
      humeral head, the greater tubercle, change of curvature and the anatomical neck.
      RESULTS: Mean maximum width was 27.4 +/- 3.4 mm and mean minimum width was 15.5
      +/- 2.8 mm. Distances between upper edge of PM tendon to: humeral head, greater
      tubercle, change of curvature and anatomical neck were respectively: 67.6 +/-
      9.98 mm, 57.8 +/- 10.3 mm, 28.7 +/- 9 mm, and 34.2 +/- 9.7 mm. CONCLUSION: Our
      study has produced an assessment of glenoid bone stock for optimal positioning of
      the glenoid implant but also to obtain a reference to determine the ideal
      location of the humeral component in the case of proximal humerus fracture.

PMID- 27716462
TI  - Electro-osmosis in inhomogeneously charged microporous media by pore-scale
      modeling.
AB  - Surface charge at solid-electrolyte interface is generally coupled with the local
      electrolyte properties (ionic concentration, pH, etc.), and therefore not as
      assumed homogeneous on the solid surfaces in the previous studies. The
      inhomogeneous charge brings huge challenges in predictions of electro-osmotic
      transport and has never been well studied. In this work, we first propose a
      classification of electro-osmosis based on a dimensionless number which is the
      ratio of the Debye length to the characteristic pore size. In the limit of thin
      electrical double layer, we establish a pore-scale numerical model for
      inhomogeneously charged electro-osmosis including four ions: Na+,Cl-,H+ and OH-.
      Based on reconstructed porous media, we simulate the electro-osmosis with
      inhomogeneous charge using lattice Boltzmann method. The nonlinear response of
      electro-osmotic velocity to applied electrical field and the reverse flow have
      been observed and analyzed.

PMID- 27716463
TI  - One dimensional SnO2 NRs/Fe2O3 NTs with dual synergistic effects for
      photoelectrocatalytic reduction CO2 into methanol.
AB  - The hydrothermal method was explored to prepare SnO2 nanorods (SnO2 NRs) with the
      special faces of (110) and (101) on the surface of Fe2O3 nanotubes (Fe2O3 NTs).
      According to the SEM and XRD results, the formation process of the hierarchically
      assembled SnO2 NRs was deduced. The SnO2 NRs/Fe2O3 NTs catalyst that had reached
      for 120 mins behaved the best photoelectrocatalytic properties. From the view of
      photocatalytic reduction, the conduction band (-0.75eV vs NHE) is negative enough
      to drive CO2 reduction, and the valence band (1.82eV) is positive enough to
      oxidize H2O to generate proton, and then the proton is used for CO2 reduction.
      From the electrocatalytic reduction point, the net CO2 reduction current density
      of the composite is 7.48 times that of Fe2O3 NTs at -1.1V, indicating that the
      electrocatalytic performance of Fe2O3 NTs is greatly enhanced by the introduction
      of 6-fold branched SnO2 NRs. The predominant reduction product is analyzed by GC
      was methanol. Herein, two synergistic effects are proved according to the
      methanol yields, one is the synergistic effect of the photocatalytic and
      electrocatalytic reduction, the other is the synergistic effect between SnO2 NRs
      and Fe2O3 NTs. The results indicated that the composite catalyst behaves
      excellent photoelectrocatalytic activity for CO2 reduction.

PMID- 27716464
TI  - Differential methylation of the circular DNA in geminiviral minichromosomes.
AB  - Geminiviral minichromosomes were purified to explore epigenetic modifications.
      The levels of methylation in their covalently closed circular DNA were examined
      with the help of methylation-dependent restriction (MdR). DNA with 12
      superhelical turns was preferentially modified, indicating minichromosomes with
      12 nucleosomes leaving an open gap. MdR digestion yielded a specific product of
      genomic length, which was cloned and Sanger-sequenced, or amplified following
      ligation-mediated rolling circle amplification and deep-sequenced (circomics).
      The conventional approach revealed a single cleavage product indicating specific
      methylations at the borders of the common region. The circomics approach
      identified considerably more MdR sites in a preferential distance to each other
      of ~200 nts, which is the DNA length in a nucleosome. They accumulated in regions
      of nucleosome-free gaps, but scattered also along the genomic components. These
      results may hint at a function in specific gene regulation, as well as in virus
      resistance.

PMID- 27716465
TI  - Evasion of early innate immune response by 2'-O-methylation of dengue genomic
      RNA.
AB  - Dengue virus (DENV) is the most prevalent mosquito-borne virus pathogen in
      humans. There is currently no antiviral therapeutic or widely available vaccine
      against dengue infection. The DENV RNA genome is methylated on its 5' cap by its
      NS5 protein. DENV bearing a single E216A point mutation in NS5 loses 2'-O
      methylation of its genome. While this mutant DENV is highly attenuated and
      immunogenic, the mechanism of this attenuation has not been elucidated. In this
      study, we find that replication of this mutant DENV is attenuated very early
      during infection. This early attenuation is not dependent on a functional type I
      interferon response and coincides with early activation of the innate immune
      response. Taken together, our data suggest that 2'-O-methylation of DENV genomic
      RNA is important for evasion of the host immune response during the very early
      stages of infection as the virus seeks to establish infection.

PMID- 27716466
TI  - Ptaquiloside from bracken in stream water at base flow and during storm events.
AB  - The bracken fern (Pteridium spp.) densely populates both open and woodland
      vegetation types around the globe. Bracken is toxic to livestock when consumed,
      and a group of potent illudane-type carcinogens have been identified, of which
      the compound ptaquiloside (PTA) is the most abundant. The highly water soluble
      PTA has been shown to be leachable from bracken fronds, and present in the soil
      and water below bracken stands. This has raised concerns over whether the
      compound might pose a risk to drinking water sources. We investigated PTA
      concentrations in a small stream draining a bracken-infested catchment at base
      flow and in response to storm events during a growth season, and included
      sampling of the bracken canopy throughfall. Streams in other bracken-dominated
      areas were also sampled at base flow for comparison, and a controlled pulse
      experiment was conducted in the field to study the in-stream dynamics of PTA.
      Ptaquiloside concentrations in the stream never exceeded 61 ng L-1 in the base
      flow samples, but peaked at 2.2 MUg L-1 during the studied storm events. The mass
      of PTA in the stream, per storm event, was 7.5-93 mg from this catchment. A clear
      temporal connection was observed between rainfall and PTA concentration in the
      stream, with a reproducible time lag of approx. 1 h from onset of rain to
      elevated concentrations, and returning rather quickly (about 2 h) to base flow
      concentration levels. The concentration of PTA behaved similar to an inert tracer
      (Cl-) in the pulse experiment over a relative short time scale (minutes-hours)
      reflecting no PTA sorption, and dispersion and dilution considerably lowered the
      observed PTA concentrations downstream. Bracken throughfall revealed a potent and
      lasting source of PTA during rainfall, with concentrations up to 169 MUg L-1,
      that did not decrease over the course of the event. In the stream, the
      throughfall contribution to PTA cannot be separated from a possible below-ground
      input from litter, rhizomes and soil. Catchment-specific factors such as the soil
      pH, topography, hydrology, and bracken coverage will evidently affect the level
      of PTA observed in the receiving stream, as well as the distance from bracken,
      but time since precipitation seems most important. Studying PTA loads and
      transport in surface streams fed by bracken-infested catchments, simply taking
      occasional grab samples will not capture the precipitation-linked pulses. The
      place and time of sampling governs the findings, and including event-based
      sampling is essential to provide a more complete picture of PTA loads to surface
      water.

PMID- 27716467
TI  - Sub-stoichiometric titanium oxide (Ti4O7) as a suitable ceramic anode for
      electrooxidation of organic pollutants: A case study of kinetics, mineralization
      and toxicity assessment of amoxicillin.
AB  - Electrochemical degradation of aqueous solutions containing antibiotic
      amoxicillin (AMX) has been extensively studied in an undivided electrolytic cell
      using a sub-stoichiometric titanium oxide (Ti4O7) anode, elaborated by plasma
      deposition. Oxidative degradation of AMX by hydroxyl radicals was assessed as a
      function of applied current and was found to follow pseudo-first order kinetics.
      The use of carbon-felt cathode enhanced oxidation capacity of the process due to
      the generation of H2O2. Comparative studies at low current intensity using
      dimensional stable anode (DSA) and Pt anodes led to the lower mineralization
      efficiencies compared to Ti4O7 anode: 36 and 41% TOC removal for DSA and Pt
      respectively compared to 69% for Ti4O7 anode. Besides, the use of boron doped
      diamond (BDD) anode under similar operating conditions allowed reaching higher
      mineralization (94%) efficiency. Although Ti4O7 anode provides a lesser
      mineralization rate compared to BDD, it exhibits better performance compared to
      the classical anodes Pt and DSA and can constitutes an alternative to BDD anode
      for a cost effective electro-oxidation process. Moreover several aromatic and
      aliphatic oxidation reaction intermediates and inorganic end-products were
      identified and a plausible mineralization pathway of AMX involving these
      intermediates was proposed.

PMID- 27716468
TI  - Potential microbial hazards from graywater reuse and associated matrices: A
      review.
AB  - Millions of decentralized graywater-reuse systems are operating worldwide. This
      water is directly accessible to household inhabitants, raising environmental and
      public health concerns. Graywater may contain a variety of harmful organisms, the
      types and numbers of which vary with source-type, storage time, and background
      levels of infection in the community source. In this review, we find that most
      studies indicate high amounts of microbial pathogens in raw graywater and
      therefore treatment and disinfection are recommended to lower possible health
      risks. Where these recommendations have been followed, epidemiological and
      quantitative microbial risk-assessment studies have found negligible health risks
      of bacterial pathogens in treated graywater. Chlorine is currently suggested as
      the most cost-effective disinfection agent for inactivating graywater bacterial
      pathogens and preventing regrowth. Various studies demonstrate that the
      introduction and diversity of pathogenic bacteria in the soil via irrigation can
      be affected by several factors, but treated graywater may not be a major
      contributor of bacterial contamination or antibiotic resistance. However, an
      accurate assessment of the infectious capabilities, exposure pathways, and
      resistance of specific pathogens, particularly viruses and antibiotic-resistant
      bacteria found in treated graywater after disinfection, as well as in the
      graywater piping, irrigated soils, plants, and associated aerosols is largely
      lacking in the literature. In addition, research shows that fecal bacterial
      indicators might not reliably indicate the presence or quantities of pathogens in
      graywater and thus, the indicator standard for graywater contamination should be
      revised.

PMID- 27716469
TI  - Characterization of nonpathogenic Listeria species isolated from food and food
      processing environment.
AB  - A total of 127 Listeria isolates from food and food processing environments,
      including 75 L. innocua, 49 L. welshimeri, 2 L. seeligeri and 1L. grayi were
      tested for susceptibility to eight antimicrobials, benzalkonium chloride (BC),
      cadmium and arsenic. The isolates were also screened for the presence of
      extrachromosomal genetic elements - plasmids, and their restriction pattern types
      were determined. All strains were susceptible to ampicillin, ciprofloxacin,
      erythromycin, gentamicin, rifampicin, trimethoprim and vancomycin. Two of the L.
      innocua isolates showed resistance to tetracycline and minocycline. The
      resistance was determined by the presence of chromosomal localization of tet(M)
      gene, which was not integrated in the transposon Tn916-Tn1545 family. Of analyzed
      isolates, 18.11% and 55.91% isolates were resistant to BC and cadmium,
      respectively, but all were susceptible to arsenic. Resistance to BC was
      correlated with resistance to cadmium - all BC resistant isolates were also
      resistant to cadmium. On the other hand, 67.61% of cadmium-resistant isolates
      were susceptible to BC, suggesting that cadmium and BC resistance were not always
      concurrent in Listeria species. 48.03% of isolates contained plasmids. The size
      of most of the identified replicons was in the range of 50-90kb. All plasmids
      were classified into 12 groups with identical restriction pattern (I-XII).
      Interestingly, plasmids belonging to the same group were determined in isolates
      of the same species. Only in one case, plasmids with I-type profile were
      identified in L. innocua and L. welshimeri. There was an association between
      resistance to BC and plasmid DNA presence: all resistant isolates carried a
      plasmid. A correlation between resistance to cadmium and plasmid carriage was
      also observed in L. innocua and L. seeligeri isolates, but among resistant L.
      welshimeri, 23.08% of isolates did not have plasmids. This may suggest that
      resistance is associated with determinants located within the chromosome. To
      elucidate the adaptation strategies and ecology of Listeria spp., it is important
      to have a better understanding of its resistance to antimicrobials and
      environmental toxicants such as heavy metals and disinfectants.

PMID- 27716470
TI  - Applicability of the EN ISO 11290-1 standard method for Listeria monocytogenes
      detection in presence of new Listeria species.
AB  - During the past six years, new species of the genus Listeria have been isolated
      from foods and other environmental niches worldwide. The Standard method EN ISO
      11290-1 that is currently under revision will include in its scope all Listeria
      species in addition to L. monocytogenes. The objective of this project was to
      evaluate the ability of the Standard EN ISO 11290-1 method to detect and identify
      the newly discovered Listeria spp., and to assess potential over-growth effects
      of the new species in mixed cultures with L. monocytogenes during each step of
      the enrichment process. This objective was addressed by the generation of
      necessary data on the behavior of the new species during the pre-enrichment and
      the enrichment steps of the reference method as well as data on their phenotypic
      characteristics on rich and selective media used for isolation and
      identification. Most of the new Listeria species developed well on selective agar
      media for Listeria, however the recovery of some species was difficult due to
      poor growth in Half Fraser and Fraser broth. Good results (consistently positive)
      were obtained for confirmation at the genus level via the catalase test, the Gram
      test and the blueish appearance test on non-selective medium, but not with the VP
      test, as most of the new species yielded a negative result. In the light of
      results obtained in co-culture experiments and inhibition tests, and considering
      the growth rates in Half Fraser and Fraser broths, the new species do not seem to
      interfere with the detection of L. monocytogenes.

PMID- 27716471
TI  - Induction and stability of oxidative stress adaptation in Listeria monocytogenes
      EGD (Bug600) and F1057 in sublethal concentrations of H2O2 and NaOH.
AB  - Food processing and food handling environments may contain residual levels of
      sanitizers or cleaners which may trigger oxidative stress adaptation in Listeria
      monocytogenes. The aim of this study was to determine the induction and stability
      of oxidative stress adaptation in L. monocytogenes EGD (Bug600) (serotype 1/2a)
      and F1057 (serotype 4b) at different concentrations and times of sublethal
      oxidative stress induced by H2O2 or sublethal alkali stress induced by NaOH at 37
      degrees C. Both L. monocytogenes Bug600 and F1057 strains showed significantly
      higher survival in lethal oxidative stress (1000ppm H2O2) after pre-exposure to
      50ppm H2O2 for 30min compared to control cells (no pre-exposure to H2O2). When
      the cells were pre-exposed to sublethal alkali stress by NaOH, the oxidative
      stress adaptation was induced within 5min in L. monocytogenes. The survival of
      both L. monocytogenes strains was increased by 2 to 4.5 logs in lethal oxidative
      stress when the cells were pre-exposed to sublethal alkali stress at pH9 from 5
      to 120min by NaOH compared to control cells (no pre-exposure to sublethal alkali
      pH). Two other alkali reagents tested (KOH and NH4OH) also induced oxidative
      stress adaptation in L. monocytogenes. For both L. monocytogenes strains, the
      oxidative stress adaptation induced by sublethal H2O2 was reversible in 30min and
      that induced by sublethal alkali stress was reversible within 60min at 37 degrees
      C in the absence of such sublethal stress. These findings show that sublethal
      oxidative or alkali stress conditions can induce oxidative stress adaptation that
      may increase the risk of survival of L. monocytogenes cells in lethal oxidative
      stress.

PMID- 27716472
TI  - Efficiency of a cleaning protocol for the removal of enterotoxigenic
      Staphylococcus aureus strains in dairy plants.
AB  - Staphylococci are considered a major concern in dairy plants mainly due to the
      intensive production flow, automation of processing plants and increased demand
      in the microbiological quality of dairy products. This study aimed to identify S.
      aureus strains isolated from three Brazilian dairy plants, evaluate the influence
      of time, temperature and contact surface on the bacterial adhesion process, as
      well as the efficiency of simulated hygiene and sanitation protocol in removing
      adhered cells. For genotypic analyses, the presence of icaA and icaD in strains
      was evaluated. Adherence assays were performed in biofilm reactor, comparing the
      influence of 2 temperatures (5 degrees C and 35 degrees C), 2 surfaces (stainless
      steel and polypropylene) and 4 contact times (3, 6, 12h and post-sanitization).
      To evaluate the process effectiveness in removing adhered cells, neutral
      detergent and sanitizing agent based on sodium hypochlorite were used in order to
      simulate the situation observed in one of the dairy plants analyzed. The presence
      of icaA and icaD genes was determined in 75.3% and 77.6% of strains,
      respectively; 70.6% of isolates showed both genes, whereas 17.6% showed no genes.
      Genes for enterotoxin production were found in all samples, relating to SEG and
      SEH toxins. The number of cells adhered on both surfaces was about 3 and 6 log10
      CFU/cm2 at temperatures of 5 degrees C and 35 degrees C, respectively, for most
      situations evaluated, with significant increase over the evaluation period. In
      general, the temperature of 35 degrees C favored greater adherence of S. aureus.
      At 5 degrees C, there was a considerable number of adhered cells, but in
      populations significantly lower than those observed at 35 degrees C. The cleaning
      and sanitizing protocol was ineffective in removing adhered cells; better
      performance of sodium hypochlorite was observed at 5 degrees C, which should be
      related to lower adherence observed at this temperature. Thus, the process was
      not able to reduce the number of S. aureus bacteria adhered on both surfaces to
      safe levels under the conditions evaluated.

PMID- 27716473
TI  - Contribution of the activated catalase to oxidative stress resistance and gamma
      aminobutyric acid production in Lactobacillus brevis.
AB  - Lactic acid bacteria (LAB) are generally sensitive to H2O2, a compound which can
      paradoxically produce themselves and lead to the growth arrest and cell death. To
      counteract the potentially toxic effects of this compound, the gene katE encoding
      a heme-dependent catalase (CAT) belonging to the family of monofunctional CATs
      was cloned from Lactobacillus brevis CGMCC1306. The enhanced homologous CAT
      expression was achieved using the NICE system. L. brevis cells with overexpressed
      CAT showed 685-fold and 823-fold higher survival when exposed to 30mmol/L of H2O2
      and long-term aerated stress (after 72h), respectively, than that of the wild
      type cells. Furtherly, the effects of activated CAT on GABA production in L.
      brevis were investigated. A GABA production level of 66.4g/L was achieved using
      two-step biotransformation that successively employed the growing and resting
      cells derived from engineering L. brevis CAT. These results demonstrated clearly
      that overexpression of the KatE gene in L. brevis led to a marked increased
      survival in oxidizing environment, and shed light on a novel feasible approach to
      enhance the GABA production level by improving the antioxidative properties.

PMID- 27716474
TI  - The impact of aging on the neural networks involved in gaze and emotional
      processing.
AB  - Normal adult aging is associated with difficulties in processing social cues to
      emotions such as anger and also altered motivation to focus more on positive than
      negative information. Gaze direction is an important modifier of the social
      signals conveyed by an emotion, for example, an angry face looking directly at
      you is considerably more threatening than an angry face looking away. In the
      present study we tested the hypothesis that older adults would show less neural
      differentiation to angry faces with direct and avert gaze compared to younger
      people, with the opposite prediction for happy faces. Healthy older (65-75 years;
      mean = 69.75) and younger (17-27 years; mean = 20.65) adults completed a
      functional magnetic resonance imaging experiment in which they were asked to
      identify happy and angry expressions displayed either with direct or averted
      gaze. While younger adults showed neural sensitivity to eye-gaze direction during
      recognition of angry expressions, older adults showed no effect of eye-gaze
      direction on neural response. In contrast, older adults showed sensitivity to eye
      gaze direction during recognition of happy expressions but younger adults did
      not. Additionally, brain-behavior correlations were conducted to investigate the
      relationships between emotion recognition and mentalizing brain network in both
      age groups. Younger (but not older) adults' social cognitive performance was
      differentially correlated with activation in 2 brain networks when looking at
      angry faces with direct compared to averted gaze. These novel findings provide
      evidence for age-related differences in the neural substrates underlying the
      capacity to integrate facial affect and eye-gaze cues. The results of this study
      suggest that age-related differences in integrating facial cues may be related to
      engagement of the mentalizing network, with potentially important implications
      for social cognitive functioning in late adulthood.

PMID- 27716475
TI  - Anti-obesity and anti-inflammatory effects of macrophage-targeted interleukin-10
      conjugated liposomes in obese mice.
AB  - Obesity is associated with chronic inflammation and is known as a major risk
      factor for several diseases including chronic kidney disease, diabetes, and
      cardiovascular diseases. Macrophages play a critical role in the development of
      obesity-induced inflammation. Efficient delivery of therapeutic anti-inflammatory
      molecules, such as interleukin (IL)-10, to macrophages can dramatically improve
      therapeutic efficacy of obesity treatments. We used liposomes containing the 'eat
      me' signal phosphatidylserine (PS) (PS-containing liposomes; PSL), which have
      macrophage targeting ability and anti-inflammatory functions, as a biomaterial
      carrier for the delivery of IL-10 to macrophages. The IL-10-conjugated PSL (PSL
      IL10) showed high affinity for macrophages. In obese mice, PSL-IL10 treatment
      exhibited significant anti-obesity and anti-inflammatory effects, such as reduced
      serum total cholesterol, adipocyte size, crown-like structures, proinflammatory
      cytokine secretion (IL-6 and tumor necrosis factor alpha) in adipose tissue,
      liver injury, hepatic steatosis, and inflammation foci, while treatment with IL
      10 or PSL alone did not. These findings suggest that the PSL-IL10 has macrophage
      targeting ability and enhanced anti-inflammatory effect due to the synergistic
      anti-inflammatory effects of IL-10 and PSL, and can be used as a macrophage
      targeted therapeutic material for inflammation-related diseases, including
      obesity.

PMID- 27716476
TI  - Temporal variation of post-accident atmospheric 137Cs in an evacuated area of
      Fukushima Prefecture: Size-dependent behaviors of 137Cs-bearing particles.
AB  - The concentrations of 137Cs in the air, which were divided into coarse (>1.1 MUm
      phi) and fine (<1.1 MUm phi) fractions of particulate matter (PM), were measured
      from October 2012 to December 2014 in an area evacuated after the Fukushima Dai
      ichi Nuclear Power Plant (FDNPP) accident. Total atmospheric 137Cs concentrations
      showed a clear seasonal variation, with high concentrations during summer and
      autumn related to the dominant easterly wind blowing from the highly
      radioactivity contaminated area. This seasonal peak was dominated by 137Cs in the
      coarse PM fraction. The 137Cs specific activity (massic 137Cs concentration) in
      the coarse PM was also found to increase significantly in summer, whereas that in
      the fine PM showed no variability during the year. These results show that coarse
      and fine 137Cs-bearing PM have different origins and behaviors in the
      resuspension process. The seasonal variation in atmospheric 137Cs concentration
      was well correlated with the mean 137Cs surface contamination (deposition
      density) around the observation site weighted by the frequency of wind direction,
      indicating that the atmospheric 137Cs concentration in the observation site was
      explained by the distribution of the 137Cs surface contamination and the
      frequency of different wind directions. We introduced a resuspension factor
      corrected for wind direction, consisting of the ratio of the atmospheric 137Cs
      concentration to the weighted mean 137Cs surface contamination, which evaluated
      the intensity of resuspension better than the conventional resuspension factor.
      This ratio ranged from 5.7 * 10-11 to 8.6 * 10-10 m-1 and gradually decreased
      during the study period.

PMID- 27716477
TI  - Maternal trajectories of cigarette use as a function of maternal age and race.
AB  - BACKGROUND: Patterns of smoking vary as a function of age and race. The goals of
      this study were to identify trajectories of maternal cigarette use over a 17-year
      span, and to determine if maternal age at first birth and race were associated
      with smoking trajectories. METHODS: Pregnant women (N=690) were recruited at an
      urban prenatal clinic. The women (13-42years old; 62% African-American, 38%
      White) were interviewed about cigarette use during pregnancy and 6, 10, 14, and
      16years postpartum. Growth mixture modeling (GMM) was used to identify
      trajectories. Regressions were used to determine if maternal age at first birth
      and race predicted trajectory class membership. RESULTS: A GMM of maternal
      cigarette use delineated 5 groups: none/unlikely to use (33%), decreasing
      likelihood of use (6%), late desistance (5%), increasing likelihood of use (17%),
      and chronic use (39%). Women who became mothers at a younger age were more likely
      to be classified as late desisters or increasingly likely to smoke. White mothers
      were more likely to be chronic smokers. Different smoking trajectories and
      predictors of trajectories were identified for the African-American and White
      mothers. Covariates including prenatal substance use, hostility, education, and
      economic hardship also differentiated smoking trajectories. CONCLUSIONS: Both
      prevention and treatment of smoking should be targeted to specific groups by age
      of first pregnancy and race. Pregnant smokers should be provided with more
      information and resources to help them avoid cigarettes during pregnancy and
      maintain abstinence after pregnancy.

PMID- 27716479
TI  - lncRNA Structure: Message to the Heart.
AB  - In this issue, Xue et al. (2016) describe the secondary structure of the heart
      specific long non-coding RNA Braveheart, leading to the discovery of a short,
      asymmetric G-rich loop that controls cardiac lineage commitment by interacting
      with the transcription factor CNBP.

PMID- 27716478
TI  - Final results and outcomes by prior bevacizumab exposure, skin toxicity, and
      hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of
      panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic
      colorectal cancer.
AB  - PURPOSE: The primary analysis of the ASPECCT study demonstrated that panitumumab
      was non-inferior to cetuximab for overall survival (OS) in patients with
      chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer
      (mCRC). Here, we report the final analysis results of ASPECCT. PATIENTS AND
      METHODS: Patients with wild-type KRAS exon 2 mCRC who progressed on or were
      intolerant to irinotecan- or oxaliplatin-based chemotherapy were randomised to
      receive panitumumab 6 mg/kg once every 2 weeks or cetuximab (400 mg/m2) followed
      by 250 mg/m2 weekly. The primary end-point was OS assessed for non-inferiority.
      Patients were followed for survival for 24 months after the last patient was
      randomised and a final analysis was conducted. No formal hypothesis testing was
      done. Post hoc analyses of outcomes by prior bevacizumab exposure, worst-grade
      skin toxicity (0-1 versus 2-4) and worst-grade hypomagnesaemia (0 versus 1-4)
      were conducted. RESULTS: Nine hundred ninety-nine patients were randomised and
      received >=1 treatment dose (panitumumab, n = 499; cetuximab, n = 500). Median OS
      was 10.2 months with panitumumab versus 9.9 months with cetuximab (hazard ratio =
      0.94; 95% confidence interval = 0.82-1.07). Median progression-free survival was
      4.2 months with panitumumab and 4.4 months with cetuximab (hazard ratio = 0.98;
      95% confidence interval = 0.87-1.12). Longer OS was observed for patients with
      increased skin toxicity and with hypomagnesaemia in both arms. Furthermore, OS
      was longer for patients with prior bevacizumab exposure treated with panitumumab
      than with cetuximab. The observed safety profiles were consistent with previous
      studies. CONCLUSION: Consistent with the primary analysis, the final analysis of
      ASPECCT showed panitumumab was non-inferior to cetuximab for OS for patients with
      chemotherapy-refractory, wild-type KRAS exon 2 mCRC. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01001377.

PMID- 27716480
TI  - Building a Regulatory Network with Short Linear Sequence Motifs: Lessons from the
      Degrons of the Anaphase-Promoting Complex.
AB  - The anaphase-promoting complex or cyclosome (APC/C) is a ubiquitin ligase that
      polyubiquitinates specific substrates at precise times in the cell cycle, thereby
      triggering the events of late mitosis in a strict order. The robust substrate
      specificity of the APC/C prevents the potentially deleterious degradation of non
      APC/C substrates and also averts the cell-cycle errors and genomic instability
      that could result from mistimed degradation of APC/C targets. The APC/C
      recognizes short linear sequence motifs, or degrons, on its substrates. The
      specific and timely modification and degradation of APC/C substrates is likely to
      be modulated by variations in degron sequence and context. We discuss the
      extensive affinity, specificity, and selectivity determinants encoded in APC/C
      degrons, and we describe some of the extrinsic mechanisms that control APC/C
      substrate recognition. As an archetype for protein motif-driven regulation of
      cell function, the APC/C-substrate interaction provides insights into the general
      properties of post-translational regulatory systems.

PMID- 27716481
TI  - Physical Proximity of Sister Chromatids Promotes Top2-Dependent Intertwining.
AB  - Sister chromatid intertwines (SCIs), or catenanes, are topological links between
      replicated chromatids that interfere with chromosome segregation. The formation
      of SCIs is thought to be a consequence of fork swiveling during DNA replication,
      and their removal is thought to occur because of the intrinsic feature of type II
      topoisomerases (Top2) to simplify DNA topology. Here, we report that SCIs are
      also formed independently of DNA replication during G2/M by Top2-dependent
      concatenation of cohesed chromatids due to their physical proximity. We
      demonstrate that, in contrast to G2/M, Top2 removes SCIs from cohesed chromatids
      at the anaphase onset. Importantly, SCI removal in anaphase requires condensin
      and coincides with the hyperactivation of condensin DNA supercoiling activity.
      This is consistent with the longstanding proposal that condensin provides a bias
      in Top2 function toward decatenation. A comprehensive model for the formation and
      resolution of toxic SCI entanglements on eukaryotic genomes is proposed.

PMID- 27716482
TI  - Histone H2A T120 Phosphorylation Promotes Oncogenic Transformation via
      Upregulation of Cyclin D1.
AB  - How deregulation of chromatin modifiers causes malignancies is of general
      interest. Here, we show that histone H2A T120 is phosphorylated in human cancer
      cell lines and demonstrate that this phosphorylation is catalyzed by hVRK1.
      Cyclin D1 was one of ten genes downregulated upon VRK1 knockdown in two different
      cell lines and showed loss of H2A T120 phosphorylation and increased H2A K119
      ubiquitylation of its promoter region, resulting in impaired cell growth. In
      vitro, H2A T120 phosphorylation and H2A K119 ubiquitylation are mutually
      inhibitory, suggesting that histone phosphorylation indirectly activates
      chromatin. Furthermore, expression of a phosphomimetic H2A T120D increased H3 K4
      methylation. Finally, both VRK1 and the H2A T120D mutant histone transformed
      NIH/3T3 cells. These results suggest that histone H2A T120 phosphorylation by
      hVRK1 causes inappropriate gene expression, including upregulated cyclin D1,
      which promotes oncogenic transformation.

PMID- 27716483
TI  - VCP/p97 Extracts Sterically Trapped Ku70/80 Rings from DNA in Double-Strand Break
      Repair.
AB  - During DNA double-strand break (DSB) repair, the ring-shaped Ku70/80 complex
      becomes trapped on DNA and needs to be actively extracted, but it has remained
      unclear what provides the required energy. By means of reconstitution of DSB
      repair on beads, we demonstrate here that DNA-locked Ku rings are released by the
      AAA-ATPase p97. To achieve this, p97 requires ATP hydrolysis, cooperates with the
      Ufd1-Npl4 ubiquitin-adaptor complex, and specifically targets Ku80 that is
      modified by K48-linked ubiquitin chains. In U2OS cells, chemical inhibition of
      p97 or siRNA-mediated depletion of p97 or its adapters impairs Ku80 removal after
      non-homologous end joining of DSBs. Moreover, this inhibition attenuates early
      steps in homologous recombination, consistent with p97-driven Ku release also
      affecting repair pathway choice. Thus, our data answer a central question
      regarding regulation of Ku in DSB repair and illustrate the ability of p97 to
      segregate even tightly bound protein complexes for release from DNA.

PMID- 27716485
TI  - SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive
      Enhancers.

PMID- 27716484
TI  - The Oscillating Stimulus Transporter Assay, OSTA: Quantitative Functional Imaging
      of Transporter Protein Activity in Time and Frequency Domains.
AB  - Transmembrane transporter proteins allow the passage of essentially all
      biologically important molecules across the lipid membranes of cells and
      organelles and are therefore of central importance to all forms of life. Current
      methods of transporter measurement, however, are lacking in several dimensions.
      Herein, a method is presented in which oscillating stimuli are presented to
      transporter-expressing cells, and activity is measured through imaging the
      corresponding oscillating responses of intracellular fluorescent sensors. This
      approach yields continuous temporal readouts of transporter activity and can
      therefore be used to measure time-dependent responses to drugs and other stimuli.
      Because of the periodic nature of the response, temporal Fourier transforms can
      be used to identify and quantify regions of interest in the xy plane and to
      overcome noise. This technique, called the Oscillating Stimulus Transporter Assay
      (OSTA), should greatly facilitate both functional characterization of
      transporters as well as high-throughput screening of drugs for transporters of
      particular pathophysiological interest.

PMID- 27716486
TI  - 53BP1 Goes Back to Its p53 Roots.
AB  - In this issue of Molecular Cell, Cuella-Martin et al. (2016) revisit the role of
      53BP1 in p53-dependent responses and find that these functions are separable from
      its widely known function in DNA repair.

PMID- 27716487
TI  - Mitochondrial Diseases: Shortcuts to Therapies and Therapeutic Shortcuts.
AB  - In this issue of Molecular Cell, Barrow et al. (2016) use two complementary
      approaches-one an assessment of a chemical library, and the other a genome-wide
      CRISPR screen-that both identify bromodomain-containing protein 4 (Brd4) as a
      therapeutic target for mtDNA diseases affecting complex I.

PMID- 27716488
TI  - Nick Your DNA, Mark Your Chromatin.
AB  - DNA damage induces chemical and structural changes in our chromatin-embedded
      genome. In a recent issue of Nature Communications, Grundy et al. (2016) identify
      a role for PARP3 in the repair of single-strand breaks and reveal that PARP3 mono
      ADP-ribosylates nucleosomal histone H2B.

PMID- 27716489
TI  - Minute-Made Data Analysis: Tools for Rapid Interrogation of Hi-C Contacts.
AB  - Juicer and Juicebox, described by Durand et al. (2016a, 2016b), are two new tools
      for fast and reliable processing of Hi-C data, providing approaches for read
      processing, multiple normalization schemes, feature annotation, and dynamic
      browsing of chromatin contacts, thus reducing arduous Hi-C analysis into an easy
      yet flexible pipeline.

PMID- 27716490
TI  - Clinical presentation of not-just right experiences (NJREs) in individuals with
      OCD: Characteristics and response to treatment.
AB  - There is increasing recognition that instead of being motivated by a desire to
      prevent harm and reduce anxiety, some obsessive-compulsive symptoms may be driven
      by a desire to get things 'just right' or 'complete' and to reduce a sense of
      discomfort. However, existing data is largely from non-clinical samples.
      Therefore, in the current paper we examine the clinical presentation of not just
      right experiences (NJREs) in patients diagnosed with OCD and compare their
      experiences to both anxious and unselected controls. Then, we provide preliminary
      data on NJREs before and after cognitive behavioral therapy (exposure and
      response prevention). First, individuals with OCD were found to report
      experiencing significantly more NJREs and being more distressed by them compared
      to anxious controls and unselected controls. Next, there was some support for the
      specificity of NJREs to feelings of incompleteness. Finally, we found that after
      completing treatment, patients reported experiencing significantly less NJREs and
      experienced less distress associated with the NJREs. In conclusion we believe
      that more work on the role of NJREs is warranted and that characterizing OCD
      symptoms as either based on harm avoidance or incompleteness/NJREs may be a
      useful framework for classifying OCD symptoms.

PMID- 27716491
TI  - Injury severity measures for predicting return-to-work after a traumatic brain
      injury.
AB  - This study compared the ability of five injury severity measures, namely the
      Abbreviated Injury Scale to the Head (AIS-H), Glasgow Coma Scale (GCS), Glasgow
      Outcome Scale (GOS), Extended Glasgow Outcome Scale (GOSE), and Injury Severity
      Score (ISS), to predict return-to-work after a traumatic brain injury (TBI).
      Furthermore, factors potentially associated with return-to-work were
      investigated. In total, 207 individuals aged <=65 years newly diagnosed with a
      TBI and employed at the time of injury were recruited and followed-up for 1year
      by telephone every 3 months. A bivariate proportional hazards model analysis
      revealed that all five injury severity measures were significantly associated
      with return-to-work after a TBI. The AIS-H and non-head ISS explained 23.8% of
      the variation in the duration of returning to work from discharge after
      hospitalization for a TBI; similarly, the GCS, GOS, GOSE, and ISS respectively
      accounted for 4.7%, 21.4%, 12.9%, and 48.4% of the variation. A multivariable
      analysis revealed that individuals with higher injury severity as measured by the
      ISS (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.92-0.97), a lack of
      autonomy in transportation (HR, 2.55; 95% CI, 1.23-5.32), cognitive impairment
      (HR, 0.47; 95% CI, 0.28-0.79), and depression (HR, 0.97; 95% CI, 0.95-0.99) were
      significantly less likely to be employed after a TBI. In conclusion, of the five
      injury severity measures, the ISS may be the most capable measure of predicting
      return-to-work after a TBI. In addition to injury severity, autonomy in
      transportation, cognitive function, and the depressive status may also influence
      the employment status during the first year after a TBI.

PMID- 27716492
TI  - Prediction of secondary crash frequency on highway networks.
AB  - Secondary crash (SC) occurrences are major contributors to traffic delay and
      reduced safety, particularly in urban areas. National, state, and local agencies
      are investing substantial amount of resources to identify and mitigate secondary
      crashes to reduce congestion, related fatalities, injuries, and property damages.
      Though a relatively small portion of all crashes are secondary, determining the
      primary contributing factors for their occurrence is crucial. The non-recurring
      nature of SCs makes it imperative to predict their occurrences for effective
      incident management. In this context, the objective of this study is to develop
      prediction models to better understand causal factors inducing SCs. Given the
      count nature of secondary crash frequency data, the authors used count modeling
      methods including the standard Poisson and Negative Binomial (NB) models and
      their generalized variants to analyze secondary crash occurrences. Specifically,
      Generalized Ordered Response Probit (GORP) framework that subsumes standard count
      models as special cases and provides additional flexibility thus improving
      predictive accuracy were used in this study. The models developed account for
      possible effects of geometric design features, traffic composition and exposure,
      land use and other segment related attributes on frequency of SCs on freeways.
      The models were estimated using data from Shelby County, TN and results show that
      annual average daily traffic (AADT), traffic composition, land use, number of
      lanes, right side shoulder width, posted speed limits and ramp indicator are
      among key variables that effect SC occurrences. Also, the elasticity effects of
      these different factors were also computed to quantify their magnitude of impact.

PMID- 27716493
TI  - Lowering thresholds for speed limit enforcement impairs peripheral object
      detection and increases driver subjective workload.
AB  - Speed enforcement reduces incidences of speeding, thus reducing traffic
      accidents. Accordingly, it has been argued that stricter speed enforcement
      thresholds could further improve road safety. Effective speed monitoring however
      requires driver attention and effort, and human information-processing capacity
      is limited. Emphasizing speed monitoring may therefore reduce resource
      availability for other aspects of safe vehicle operation. We investigated whether
      lowering enforcement thresholds in a simulator setting would introduce further
      competition for limited cognitive and visual resources. Eighty-four young adult
      participants drove under conditions where they could be fined for travelling 1,
      6, or 11km/h over a 50km/h speed-limit. Stricter speed enforcement led to greater
      subjective workload and significant decrements in peripheral object detection.
      These data indicate that the benefits of reduced speeding with stricter
      enforcement may be at least partially offset by greater mental demands on
      drivers, reducing their responses to safety-critical stimuli on the road. It is
      likely these results under-estimate the impact of stricter speed enforcement on
      real-world drivers who experience significantly greater pressures to drive at or
      above the speed limit.

PMID- 27716494
TI  - Mechanisms behind distracted driving behavior: The role of age and executive
      function in the engagement of distracted driving.
AB  - Performing secondary tasks, such as texting while driving, is associated with an
      increased risk of motor vehicle collisions (MVCs). While cognitive processes,
      such as executive function, are involved in driving, little is known about the
      relationship between executive control and willingness to engage in distracted
      driving. This study investigated the relationship between age, behavioral
      manifestations of executive function, and self-reported distracted driving
      behaviors. Executive difficulty (assessed with the BRIEF-A) as well as
      demographics (age and gender) was considered as possible predictors of engagement
      in distracted driving behaviors. Fifty-nine young, middle, and older adults self
      reported executive difficulty and weekly engagement in distracted driving
      behaviors. Results revealed that while partially accounted for by age, global
      executive difficulty was uniquely related to engagement in distracted driving
      behaviors. Older age was associated with fewer weekly self-reported distracted
      driving behaviors while higher self-reported executive difficulty was associated
      with more frequent weekly engagement in distracted behavior. No significant
      differences were found between young and middle-aged adults on distracted driving
      behaviors. Findings conclude that distracted driving is a ubiquitous phenomenon
      evident in drivers of all ages. Possible mechanisms underlying distracted driving
      behavior could potentially be related to deficits in executive function.

PMID- 27716495
TI  - Examining racial bias as a potential factor in pedestrian crashes.
AB  - INTRODUCTION: In the US people of color are disproportionately affected by
      pedestrian crashes. The purpose of this study was to examine the potential for
      racial bias in driver yielding behaviors at midblock crosswalks in low and high
      income neighborhoods located in the sprawling metropolitan area of Las Vegas, NV.
      METHODS: Participants (1 white, 1 black female) crossed at a midblock crosswalk
      on a multilane road in a low income and a high income neighborhood. Trained
      observers recorded (1) number of cars that passed in the nearest lane before
      yielding while the pedestrian waited near the crosswalk at the curb (2) number of
      cars that passed through the crosswalk with the pedestrian in the same half of
      the roadway. RESULTS: The first car in the nearest lane yielded to the pedestrian
      while they waited at the curb 51.5% of the time at the high income and 70.7% of
      the time at the low income crosswalk. Two way ANOVAs found an interaction effect
      between income and race on yielding behaviors. Simple effects for income revealed
      that at the high income crosswalk, drivers were less likely to yield to the white
      pedestrian while she waited at the curb (F(1,122)=11.18;p=0.001), and were less
      likely to yield to the black pedestrian while she was in the same half of the
      roadway at the high income crosswalk (F(1,124)=4.40;p=0.04). Simple effects for
      race showed significantly more cars passed through the crosswalk while the black
      pedestrian was in the roadway compared to the white pedestrian at the high income
      crosswalk (F(1,124)=6.62;p=0.01). CONCLUSIONS: Bias in driver yielding behavior
      may be one influencing factor in higher rates of pedestrian crashes for people of
      color.

PMID- 27716497
TI  - Knockout! Knockout! Who's Not There?

PMID- 27716496
TI  - Bone-targeted therapy use in patients with bone metastases from lung cancer: A
      systematic review of randomized controlled trials.
AB  - BACKGROUND: Patients with advanced lung cancer commonly have bone metastases.
      Compared with other malignancies, the use of bone-targeted agents (e.g.
      bisphosphonates and denosumab) is less common in lung cancer patients. This may
      be due to the perception that bone-targeted agents are less effective in this
      population. OBJECTIVE: To perform a systematic review to evaluate data from
      randomized trials of bone-targeted agents in lung cancer patients with bone
      metastases. METHODS: A systematic search of Medline, Embase and the Cochrane
      Register of Controlled Trials through May 2015 was performed. Randomized trials
      of bone-targeted therapies in lung cancer patients with bone metastases were
      sought. Outcomes studied included skeletal related events (SREs), pain, quality
      of life, progression-free survival and overall survival. Random effects meta
      analyses were planned if studies were judged homogeneous. RESULTS: Of 632
      abstracts, 17 publications describing 13 studies were included. Sample sizes
      ranged between 50 and 1776. Of 3379 patients, 1903 had lung cancer, with subgroup
      data available for 8 of 13 studies. Patient demographics were comparable, but
      enrollment criteria and endpoints were heterogeneous across studies, precluding
      meta-analysis. Study-specific results suggested that bone-modifying agents reduce
      the incidence of SREs and bone pain in lung cancer patients. Three studies
      suggested a survival benefit. CONCLUSION: Data from included trials suggests
      benefit of bone-targeted agents in lung cancer for the prevention of SREs and
      bone pain. There is a trend toward improvement in overall survival and
      progression-free survival, although further research is needed. Impact on quality
      of life and key subgroups for benefit both require future research.

PMID- 27716498
TI  - Rett Syndrome and the Ongoing Legacy of Close Clinical Observation.
AB  - This year marks the 50th anniversary of the publication of Andreas Rett's report
      on 22 girls who developed a peculiar and devastating neurological disorder that
      later came to bear his name. On this occasion, we reflect on the progress that
      has occurred in understanding Rett Syndrome, development of potential treatments,
      and the ramifications that Rett research has had on the fields of neurobiology
      and genetics.

PMID- 27716499
TI  - Empowering Older Antibiotics.
AB  - Avycaz combines an older cephalosporin antibiotic, ceftazidime, and the beta
      lactamase inhibitor avibactam. Ceftazidime targets penicillin-binding proteins
      (PBPs) in the bacterial periplasm that are required for cell wall synthesis.
      Avibactam blocks beta-lactamases (beta-L) in the periplasm, which would otherwise
      inactivate the antibiotics resulting in drug resistance.

PMID- 27716500
TI  - Remembering the Past: A New Form of Protein-Based Inheritance.
AB  - A comprehensive analysis uncovered a set of yeast proteins promoting protein
      based inheritance that shares many of the non-Mendelian properties of prions.
      Lacking any sequence or structural signatures of known prions, these proteins
      represent a new class of non-amyloid, protein-based epigenetic determinants that
      can control phenotype without impacting genotype.

PMID- 27716501
TI  - Customizing Functionality and Payload Delivery for Receptor-Engineered T Cells.
AB  - Adoptive immunotherapy using receptor engineering to achieve specific tumor
      targeting by T cells holds much promise for advancing cancer therapy. Here, two
      studies by Boice et al. and Roybal et al. provide distinct and potentially
      complimentary approaches to improve the efficacy and curb potential toxicities of
      this approach.

PMID- 27716502
TI  - To Be or Not Be a (Functional) Antibody Against TB.
AB  - In this issue of Cell, Lu et al. provide important insights on the efficacy of
      human antibodies to Mycobacterium tuberculosis and on how functional
      heterogeneity of the antibody response may explain a century of contradictory
      evidence for the role of humoral immunity in defense against tuberculosis.

PMID- 27716503
TI  - Coordination of Two Genomes by Mitochondrial Translational Plasticity.
AB  - The dual genetic origin of mitochondrial respiratory chain complexes leads to the
      synthesis of subunits by mitochondrial and cytosolic ribosomes. Now, Richter
      Dennerlein et al. report that membrane-integrated assembly factors associate with
      ribosome nascent chain complexes in human mitochondria to coordinate
      translational plasticity with the import of subunits from the cytosol.

PMID- 27716504
TI  - PIWI Takes a Giant Step.
AB  - piRNA guides the action of PIWI proteins to silence deleterious transposons in
      animal reproductive tissues. Biogenesis of piRNA-induced silencing complex
      (piRISC) involves a multi-step process. In this issue, Matsumoto et al. report
      the first crystal structure of a PIWI-clade protein displaying a guide RNA, ready
      for action.

PMID- 27716505
TI  - Abiotic Stress Signaling and Responses in Plants.
AB  - As sessile organisms, plants must cope with abiotic stress such as soil salinity,
      drought, and extreme temperatures. Core stress-signaling pathways involve protein
      kinases related to the yeast SNF1 and mammalian AMPK, suggesting that stress
      signaling in plants evolved from energy sensing. Stress signaling regulates
      proteins critical for ion and water transport and for metabolic and gene
      expression reprogramming to bring about ionic and water homeostasis and cellular
      stability under stress conditions. Understanding stress signaling and responses
      will increase our ability to improve stress resistance in crops to achieve
      agricultural sustainability and food security for a growing world population.

PMID- 27716506
TI  - Field Guide to Plant Model Systems.
AB  - For the past several decades, advances in plant development, physiology, cell
      biology, and genetics have relied heavily on the model (or reference) plant
      Arabidopsis thaliana. Arabidopsis resembles other plants, including crop plants,
      in many but by no means all respects. Study of Arabidopsis alone provides little
      information on the evolutionary history of plants, evolutionary differences
      between species, plants that survive in different environments, or plants that
      access nutrients and photosynthesize differently. Empowered by the availability
      of large-scale sequencing and new technologies for investigating gene function,
      many new plant models are being proposed and studied.

PMID- 27716508
TI  - Regulation of the CUL3 Ubiquitin Ligase by a Calcium-Dependent Co-adaptor.
AB  - The ubiquitin ligase CUL3 is an essential regulator of neural crest specification
      whose aberrant activation has been linked to autism, schizophrenia, and
      hypertension. CUL3 exerts its roles by pairing with ~90 distinct substrate
      adaptors, yet how the different CUL3-complexes are activated is poorly
      understood. Here, we show that CUL3 and its adaptor KLHL12 require two calcium
      binding proteins, PEF1 and ALG2, for recognition of their substrate SEC31. PEF1
      and ALG2 form a target-specific co-adaptor that translates a transient rise in
      cytosolic calcium levels into more persistent SEC31 ubiquitylation, which in turn
      triggers formation of large COPII coats and promotes collagen secretion. As
      calcium also instructs chondrocyte differentiation and collagen synthesis,
      calcium-dependent control of CUL3KLHL12 integrates collagen secretion into
      broader programs of craniofacial bone formation. Our work, therefore, identifies
      both calcium and CUL3 co-adaptors as important regulators of ubiquitylation
      events that control human development.

PMID- 27716507
TI  - Host-Protozoan Interactions Protect from Mucosal Infections through Activation of
      the Inflammasome.
AB  - While conventional pathogenic protists have been extensively studied, there is an
      underappreciated constitutive protist microbiota that is an integral part of the
      vertebrate microbiome. The impact of these species on the host and their
      potential contributions to mucosal immune homeostasis remain poorly studied.
      Here, we show that the protozoan Tritrichomonas musculis activates the host
      epithelial inflammasome to induce IL-18 release. Epithelial-derived IL-18
      promotes dendritic cell-driven Th1 and Th17 immunity and confers dramatic
      protection from mucosal bacterial infections. Along with its role as a
      "protistic" antibiotic, colonization with T. musculis exacerbates the development
      of T-cell-driven colitis and sporadic colorectal tumors. Our findings demonstrate
      a novel mutualistic host-protozoan interaction that increases mucosal host
      defenses at the cost of an increased risk of inflammatory disease.

PMID- 27716509
TI  - A Force-Induced Directional Switch of a Molecular Motor Enables Parallel
      Microtubule Bundle Formation.
AB  - Microtubule-organizing centers (MTOCs) nucleate microtubules that can grow
      autonomously in any direction. To generate bundles of parallel microtubules
      originating from a single MTOC, the growth of multiple microtubules needs to
      coordinated, but the underlying mechanism is unknown. Here, we show that a
      conserved two-component system consisting of the plus-end tracker EB1 and the
      minus-end-directed molecular motor Kinesin-14 is sufficient to promote parallel
      microtubule growth. The underlying mechanism relies on the ability of Kinesin-14
      to guide growing plus ends along existing microtubules. The generality of this
      finding is supported by yeast, Drosophila, and human EB1/Kinesin-14 pairs. We
      demonstrate that plus-end guiding involves a directional switch of the motor due
      to a force applied via a growing microtubule end. The described mechanism can
      account for the generation of parallel microtubule networks required for a broad
      range of cellular functions such as spindle assembly or cell polarization.

PMID- 27716511
TI  - SnapShot: Signaling in Symbiosis.
AB  - The nitrogen-fixing Rhizobium-legume partnership is presently the best understood
      of all host-microbe symbioses. Bacterial and plant partners signal across
      developmental time and space.

PMID- 27716510
TI  - Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells.
AB  - Understanding human embryonic ventral midbrain is of major interest for
      Parkinson's disease. However, the cell types, their gene expression dynamics, and
      their relationship to commonly used rodent models remain to be defined. We
      performed single-cell RNA sequencing to examine ventral midbrain development in
      human and mouse. We found 25 molecularly defined human cell types, including five
      subtypes of radial glia-like cells and four progenitors. In the mouse, two mature
      fetal dopaminergic neuron subtypes diversified into five adult classes during
      postnatal development. Cell types and gene expression were generally conserved
      across species, but with clear differences in cell proliferation, developmental
      timing, and dopaminergic neuron development. Additionally, we developed a method
      to quantitatively assess the fidelity of dopaminergic neurons derived from human
      pluripotent stem cells, at a single-cell level. Thus, our study provides insight
      into the molecular programs controlling human midbrain development and provides a
      foundation for the development of cell replacement therapies.

PMID- 27716512
TI  - Adolescent self-injurers: Comparing non-ideators, suicide ideators, and suicide
      attempters.
AB  - Adolescent non-suicidal self-injury (NSSI) and suicidality are serious health
      concerns; however, factors that contribute to the transition from NSSI to suicide
      ideation and suicide attempts are unclear. To address this gap, we investigated
      whether demographic characteristics, child maltreatment, and psychiatric factors
      are associated with the level suicidality among adolescents with a history of
      self-injury. Participants were three groups of adolescent inpatient self-injurers
      (n = 397, 317 female), aged 13-18 years (M = 15.44, SD = 1.36): (a) non-ideators
      (n = 96; no current suicide ideation and no lifetime suicide attempts), (b)
      suicide ideators (n = 149; current ideation and no lifetime attempts), and (c)
      suicide attempters (n = 152; current ideation and at least one lifetime attempt).
      Participants completed interviews assessing psychiatric diagnoses, suicidality,
      and NSSI characteristics, as well as questionnaires on childhood trauma,
      psychiatric symptoms, and risky behavior engagement. Depression severity was
      associated with greater odds being a suicide ideator (p < 0.001, OR = 1.04) and
      an attempter (p < 0.001, OR = 1.05) compared to a non-ideator. Suicide attempters
      used more NSSI methods and reported greater risky behavior engagement than non
      ideators (p = 0.03, OR = 1.29 and p = 0.03, OR = 1.06, respectively) and ideators
      (p = 0.015, OR = 1.25 and p = 0.04, OR = 1.05, respectively); attempters used
      more severe NSSI methods (e.g., burning). Our results identify a wide range of
      risk markers for increasing lethality in a sample at high risk for suicide
      mortality; future research is needed to refine risk assessments for adolescent
      self-injurers and determine the clinical utility of using risk markers for
      screening and intervention.

PMID- 27716515
TI  - Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic
      Patent Ductus Arteriosus.

PMID- 27716514
TI  - Mood disorders and biological rhythms in young adults: A large population-based
      study.
AB  - BACKGROUND: It is known that sleep disturbance has been considered a trait-marker
      of mood disorders. However, the role of disruptions in biological rhythms, such
      as eating, activity, and social patterns, needs to be better understood. AIM: To
      assess the differences in biological rhythms in subjects with bipolar disorder,
      major depressive disorder, and healthy controls. We also tested the association
      between disruptions of biological rhythms and circadian preferences. METHODS: A
      cross-sectional, population-based study with a representative sample of 1023
      young adults. Bipolar disorder and depression were diagnosed using The Mini
      International Neuropsychiatric Interview - PLUS and DSM Structured Clinical
      Interview. Self-reported biological rhythms and circadian preference were
      assessed using the Biological Rhythm Interview of Assessment in Neuropsychiatry
      (BRIAN). RESULTS: Bipolar disorders and depression subjects presented higher
      rates of disruption in biological rhythms when compared to healthy controls even
      after adjusting for sex, socioeconomic status, alcohol, tobacco, illicit drug
      use, anxiety disorder and psychotropic medication use. Euthymic subjects showed
      higher biological rhythm disruption when compared to controls. Higher disruption
      in biological rhythms was observed in subjects with evening preferences.
      CONCLUSION: Higher disruption in biological rhythms occurs in individuals with
      depression and bipolar disorder even on periods of euthymia.

PMID- 27716513
TI  - Specific expectancies are associated with symptomatic outcomes and side effect
      burden in a trial of chamomile extract for generalized anxiety disorder.
AB  - OBJECTIVE: Patient expectancies are hypothesized to contribute to the efficacy
      and side effects of psychiatric treatments, but little research has investigated
      this hypothesis in the context of psychopharmacological therapies for anxiety. We
      prospectively investigated whether expectancies predicted efficacy and adverse
      events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for
      confounding patient characteristics correlating with outcomes. METHODS:
      Expectancies regarding treatment efficacy and side effects were assessed at
      baseline of an eight week open-label phase of a trial of chamomile for
      Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD
      7 scores, with clinical response and treatment-emergent side-effects as secondary
      outcomes. Expectancies were used to predict symptomatic and side-effect outcomes.
      RESULTS: Very few baseline patient characteristics predicted either type of
      expectancy. Controlling for a patient's predicted recovery based on their
      baseline characteristics, higher efficacy expectancies at baseline predicted
      greater change on the GAD-7 (adjusted beta = -0.19, p = 0.011). Efficacy
      expectancies also predicted a higher likelihood of attaining clinical response
      (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect
      expectancies reported more side effects (adjusted log expected count = 0.26, p =
      0.038). Efficacy expectancies were unrelated to side effect reports (log expected
      count = -0.05, p = 0.680), and side effect expectancies were unrelated to
      treatment efficacy (beta = 0.08, p = 0.306). CONCLUSIONS: Patients entering
      chamomile treatment for GAD with more favorable self-generated expectancies for
      the treatment experience greater improvement and fewer adverse events. Aligning
      patient expectancies with treatment selections may optimize outcomes.
      REGISTRATION: Trial Number NCT01072344 at ClinicalTrials.gov.

PMID- 27716517
TI  - Enhanc(er)ing Skin Stem Cells.
AB  - In this issue of Cell Stem Cell, Rinaldi et al. (2016) find an unexpected role
      for the de novo DNA methyltransferases Dnmt3a and Dnmt3b in the regulation of
      enhancers. Their findings provide new insight into how regulation of enhancer
      activity through DNA methylation can have dramatic consequences on epidermal stem
      cell fate decisions.

PMID- 27716518
TI  - Digit Tip Regeneration and Beyond: Schwann Cell Progenitors to the Rescue.
AB  - Digit tip regeneration following amputation is an innate response in some
      mammals, including mice. In this issue of Cell Stem Cell, Johnston et al. (2016)
      show that Schwann cell precursors are necessary for this process and can rescue
      regeneration in denervated digit tips through secretion of pro-regenerative
      factors including OSM and PDGF-AA.

PMID- 27716519
TI  - A Glycolytic Solution for Pluripotent Stem Cells.
AB  - Glycolysis is an essential component of cellular metabolism associated with
      pluripotent stem cells (PSCs). Two new papers, one by Gu et al. (2016) in this
      issue of Cell Stem Cell and one by Zhang et al. (2016) in Cell Reports,
      demonstrate that glycolytic flux is dynamically increased in human primed PSCs
      upon feeder-free cultivation or conversion into the naive state.

PMID- 27716520
TI  - Out of Many, One: Computational Reconstruction of Mouse Skin using Single-Cell
      Transcriptomics.
AB  - Mammalian skin is a complex and heterogeneous tissue with several distinct
      compartments and stem cell populations. Joost et al. (2016) now use single-cell
      RNaseq to comprehensively reconstruct this complexity, revealing spatial and
      pseudotemporal differences between transcriptional programs in distinct
      compartments and a common basal program in skin stem cell populations.

PMID- 27716521
TI  - Human ESC-Derived Interneurons Improve Major Consequences of Spinal Cord Injury.
AB  - Beyond impaired motor and sensory function, neuropathic pain and loss of bladder
      control caused by spinal cord injuries (SCIs) can severely affect quality of
      life. In this issue of Cell Stem Cell, Fandel et al. (2016) show that
      transplanted human ESC-derived cells biased to produce inhibitory interneurons
      significantly improve pain and bladder function in rodent SCI models.

PMID- 27716522
TI  - Monitoring Tissue Regeneration at Single-Cell Resolution.
AB  - For tissue regeneration researchers, seeing is believing. Here, we consider
      advances in genetic tools, imaging platforms, and quantification capabilities
      that are turning previously unattainable goals, like in toto capture of cellular
      and subcellular behaviors in regenerating tissues, into reality.

PMID- 27716523
TI  - Layer-by-layer nanocoating of live Bacille-Calmette-Guerin mycobacteria with
      poly(I:C) and chitosan enhances pro-inflammatory activation and bactericidal
      capacity in murine macrophages.
AB  - Tuberculosis (TB) is a major disease burden globally causing more than 1.5
      million deaths per year. The attenuated live vaccine strain Bacille Calmette
      Guerin (BCG), although providing protection against childhood TB, is largely
      ineffective against adult pulmonary TB. A major aim therefore is to increase the
      potency of the BCG vaccine to generate stronger and more sustained immunity
      against TB. Here, we investigated the use of layer-by-layer (LbL) nanocoating of
      the surface of live BCG with several layers of polyinosinic-polycytidylic acid
      (poly(I:C)), a strong inducer of cell-mediated immunity, and the biodegradable
      polysaccharide chitosan to enhance BCG immunogenicity. Nanocoating of live BCG
      did not affect bacterial viability or growth in vitro but induced killing of the
      BCG in infected mouse bone marrow-derived macrophages and enhanced macrophage
      production of pro-inflammatory cytokines and expression of surface co-stimulatory
      molecules relative to uncoated BCG. In addition, poly(I:C) surface-coated BCG,
      but not BCG alone or together with soluble poly(I:C), induced high production of
      nitric oxide (NO) and IL-12. These results argue that BCG and surface absorbed
      poly(I:C) act in a synergistic manner to elicit pro-inflammatory macrophage
      activation. In conclusion, nanocoating of live BCG with the immunostimulatory
      agent poly(I:C) may be an appropriate strategy to enhance and modulate host
      responses to the BCG vaccine.

PMID- 27716524
TI  - Subcellular cell geometry on micropillars regulates stem cell differentiation.
AB  - While various material factors have been shown to influence cell behaviors,
      recent studies started to pay attention to the effects of some material cues on
      "subcellular" geometry of cells, such as self-deformation of cell nuclei. It is
      particularly interesting to examine whether a self deformation happens
      discontinuously like a first-order transition and whether subcellular geometry
      influences significantly the extent of stem cell differentiation. Herein we
      prepared a series of micropillar arrays of poly(lactide-co-glycolide) and
      discovered a first-order transition of nuclear shape as a function of micropillar
      height under the examined section area and interspacing of the pillars. The
      deformed state of the nuclei of mesenchymal stem cells (MSCs) was well maintained
      even after osteogenic or adipogenic induction for several days. The nuclear
      deformation on the micropillar arrays was accompanied with smaller projected
      areas of cells, but led to an enhanced osteogenesis and attenuated adipogenesis
      of the MSCs, which is different from the previously known relationship between
      morphology and differentiation of stem cells on flat substrates. Hence, the
      present study reveals that the geometry of cell nuclei may afford a new cue to
      regulate the lineage commitment of stem cells on the subcellular level.

PMID- 27716525
TI  - Activation induced cytidine deaminase mutant (AID-His130Pro) from Hyper IgM 2
      patient retained mutagenic activity on SHM artificial substrate.
AB  - Activation induced cytidine deaminase (AID) is an essential enzyme for class
      switch recombination (CSR) and somatic hypermutation (SHM) during secondary
      immune response. Mutations in the AICDA gene are responsible for Hyper IgM 2
      syndrome where both CSR and SHM or only CSR are affected. Indeed, triggering
      either of the two mechanisms requires the DNA deamination activity of AID.
      Besides, different domains of AID may be differentially involved in CSR and SHM
      through their interaction with specific cofactors. Herein, we studied the AID
      induced SHM activity of the AID-His130Pro mutant identified in a patient with
      Hyper IgM 2 syndrome. AID mutagenic activity was monitored by the reversion of
      nonsense mutations of the EGFP gene assessed by flow cytometry. We found that the
      His130Pro mutation, which affects CSR, preserves AID mutagenic activity. Indeed,
      the His130 residue is located in a putative specific CSR region in the APOBEC
      like domain, known to involve CSR specific cofactors that probably play a major
      role in AID physiological activities.

PMID- 27716526
TI  - Evolution and demography of the great apes.
AB  - The great apes are the closest living relatives of humans. Chimpanzees and
      bonobos group together with humans, while gorillas and orangutans are more
      divergent from humans. Here, we review insights into their evolution pertaining
      to the topology of species and subspecies and the reconstruction of their
      demography based on genome-wide variation. These advances have only become
      possible recently through next-generation sequencing technologies. Given the
      close relationship to humans, they provide an important evolutionary context for
      human genetics.

PMID- 27716527
TI  - Nanomedicine-based paclitaxel induced apoptotic signaling pathways in A562
      leukemia cancer cells.
AB  - In the present study, we have synthesized an amphiphilic pH-sensitive structure
      of poly(ethylene glycol) methyl ether-b-(poly lactic acid-co-poly(b-amino
      esters)) (MPEG-b-(PLA-co-PAE)) to load paclitaxel to increase the therapeutic
      efficacy in leukemia. The micelles exhibit excellent drug-loading capacities for
      paclitaxel (PTX) and exhibited a typical pH-responsive drug release pattern. The
      release of PTX from the micelles was significantly accelerated by decreasing pH
      from 7.4 to 5.0 which just fitted the pathological process. The most important
      advantage of this design is that the polymeric micelles provide an effective
      approach for rapid transport of cargo into the cytosol, which significantly
      increases the antitumor efficacy of PTX against K562 cancer cells. Paclitaxel
      loaded polymer micelles (PTX-M) showed significantly higher cytotoxic effect than
      that of free PTX. The PTX-M exhibited a superior apoptosis effect in cancer cells
      compared to that of free PTX at all time points. We have showed that the PTX-M
      activated upstream of apoptosis signaling and inhibited the anti-apoptotic
      factors. The PTX-M remarkably increased the upregulation of Bax, caspase-3,
      caspase-9, and PARP-1 expression and downregulated the Bcl-2 expression in K562
      cancer cells. The results show that PTX-M induced cell apoptosis through
      intrinsic apoptotic signaling pathway. Importantly, PTX had a remarkably
      prolonged plasma circulation time after administration of PTX-M. Overall, this
      novel cancer specific, pH-responsive, and potentially in vivo stable unimolecular
      micelles may provide a very promising approach for targeted cancer therapy in the
      effective treatment of Leukemia.

PMID- 27716528
TI  - PEG-mimetic peptoid reduces protein fouling of polysulfone hollow fibers.
AB  - Biofouling is a persistent problem for membranes exposed to blood or other
      complex biological fluids, affecting surface structure and hindering performance.
      In this study, a peptoid with 2-methoxyethyl (NMEG5) side chains was immobilized
      on polysulfone hollow fiber membranes to prevent protein fouling. The successful
      attachment of NMEG5 to the polysulfone surface was confirmed by X-ray
      photoelectron spectroscopy and an increase in hydrophilicity was confirmed by
      contact angle analysis. The NMEG5-modified surface was found to resist fouling
      with bovine serum albumin, lysozyme, and adsorbed significantly less fibrinogen
      as compared with other published low-fouling surfaces. Due to the low fouling
      nature and increased biocompatibility of the NMEG5 coated membranes, they have
      potential applicability in numerous biomedical applications including artificial
      lungs and hemodialysis.

PMID- 27716529
TI  - Interaction of curcumin with 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine
      liposomes: Intercalation of rhamnolipids enhances membrane fluidity, permeability
      and stability of drug molecule.
AB  - Stability of curcumin in neutral and alkaline buffer conditions has been a
      serious concern for its medicinal applications. We demonstrate that the stability
      of curucmin can be improved in 1,2-Dioctadecanoyl-sn-glycero-3-phosphocholine
      (DSPC) liposomes. Curcumin strongly partition into liquid crystalline phase
      compared to solid gel phase of DSPC liposomes. Variation of fluorescence
      intensity of curcumin associated with liposomes with temperature successfully
      determines phase transition temperature of DSPC liposomes. However, at higher
      molar ratio curcumin can influence phase transition temperature by intercalating
      into deep hydrophobic layer of liposomes and facilitating fusion of two membrane
      phases. Rhamnolipids (RLs) are recently being applied for various biomedical
      applications. Here, we have explored new insight on intercalation of rhamnolipids
      with DSPC liposomes. Intercalation of rhamnolipids exceptionally increases
      partition of curcumin into solid gel phase of DSPC liposomes, whereas this
      increase is moderate in liquid crystalline phase. Fluorescence quenching study
      establishes that permeability and fluidity of the DSPC liposomes are enhanced in
      the presence of RLs. Membrane permeability and fluidity can be improved further
      by increasing the percentage of RLs in DSPC liposomes. The phase transition
      temperature of DSPC liposomes decreases with increase in percentage of RLs in
      DSPC liposomes by encouraging fusion between solid gel and liquid crystalline
      phases. Intercalation of RLs is found to further boost stability of drug,
      curcumin, in DSPC liposomes. Thus, mixing RLs with DSPC liposomes could
      potentially serve as a good candidate for drug delivery application.

PMID- 27716530
TI  - Naringin protects against lipopolysaccharide-induced cardiac injury in mice.
AB  - Previous research has demonstrated that lipopolysaccharide (LPS) can induce
      sepsis and lead to myocardial dysfunction. Naringin has various biological
      activities in LPS-induced sepsis. In this study, our aim was to investigate the
      effects of Naringin on LPS-induced cardiac injury and clarify its potential
      mechanism. We found that in vivo treatment with Naringin significantly
      ameliorated body weight loss, and attenuated cardiac histopathological changes
      after LPS challenge. Furthermore, Naringin inhibited LPS-induced increase of TNF
      alpha, IL-1beta and IL-6 activities to alleviate inflammatory response in heart.
      Moreover, Naringin supplement dramatically increased SOD levels, and prevented
      MDA levels to ameliorate oxidative stress compared with the LPS group in heart.
      Lastly, treatment with Naringin also significantly decreased the ratio of BAX to
      BCL-2 to resist apoptosis in heart. It is concluded that Naringin may be a
      promising therapeutic agent on LPS-induced cardiac injury by anti-inflammatory,
      anti-oxidant and anti-apoptotic effects.

PMID- 27716531
TI  - Chlorhexidine possesses unique cytotoxic actions in rat thymic lymphocytes: Its
      relation with electrochemical property of membranes.
AB  - Chlorhexidine (CHX) is an antibacterial agent used in various types of
      pharmaceutical products. Therefore, CHX is easily found around us. Owing to its
      positive charge, the electrochemical property of cell membranes was assumed to be
      a key point of cytotoxic action of CHX. Depolarization of membranes attenuated
      the cytotoxic action of CHX in rat thymic lymphocytes. CHX interfered with
      annexin V binding to membranes. Manipulations to induce exposure of
      phosphatidylserine on the outer membrane surface augmented the cytotoxic action
      of CHX, indicating that changes in the electrochemical property of membranes
      affected the cytotoxic action of CHX. Hence, CHX might kill cells physiologically
      undergoing apoptosis, resulting instead in necrotic cell death. However, the
      threshold CHX concentration in this in vitro study was slightly higher than blood
      CHX concentrations observed clinically. Therefore, these results may support the
      safety of CHX use although CHX possesses unique cytotoxic actions described in
      this study.

PMID- 27716532
TI  - Potential anti-inflammatory natural products from marine algae.
AB  - Inflammatory diseases have become one of the leading causes of health issue
      throughout the world, having a considerable influence on healthcare costs. With
      the emerging developments in natural product, synthetic and combinatorial
      chemistry, a notable success has been achieved in discovering natural products
      and their synthetic structural analogs with anti-inflammatory activity. However,
      many of these therapeutics have indicated detrimental side effects upon prolonged
      usage. Marine algae have been identified as an underexplored reservoir of unique
      anti-inflammatory compounds. These include polyphenols, sulfated polysaccharides,
      terpenes, fatty acids, proteins and several other bioactives. Consumption of
      these marine algae could provide defense against the pathophysiology of many
      chronic inflammatory diseases. With further investigation, algal anti
      inflammatory phytochemicals have the potential to be used as therapeutics or in
      the synthesis of structural analogs with profound anti-inflammatory activity with
      reduced side effects. The current review summarizes the latest knowledge about
      the potential anti-inflammatory compounds discovered from marine algae.

PMID- 27716533
TI  - Curcumin-cyclodextrin complexes enhanced the anti-cancer effects of curcumin.
AB  - Curcumin (CUR), as a yellow pigment in the spice turmeric (Curcuma longa),
      possessed a pleiotropic application containing cancer therapy. Due to its poor
      oral bioavailability, the objective of this study was to investigate the use of
      curcumin-cyclodextrin complexes (CD15) as an approach to cancer chemoprevention.
      In this study, CUR encapsulation into the beta-cyclodextrin (CD) cavity was
      achieved by the saturated aqueous solution method. CD15 was characterized by
      Fourier transform infrared (FTIR) and UV spectra analyses. An optimized CD15 was
      evaluated by cellular uptake and anti-cancer activity. As a result, CD15 enhanced
      curcumin delivery and improved its therapeutic efficacy compared with free
      curcumin in vivo and in vitro. Therefore, through regulation of MAPK/NF-kappaB
      pathway, CD15 up-regulated p53/p21 pathway, down-regulated CyclinE-CDK2
      combination and increased Bax/caspase 3 expression to induce cellar apoptosis and
      G1-phase arrest. In conclusion, these results suggested that CD15 formulation
      should be used as a system for improving curcumin delivery and its therapeutic
      efficacy in lung cancer.

PMID- 27716534
TI  - Low dose extended exposure to saxitoxin and its potential neurodevelopmental
      effects: A review.
AB  - Saxitoxin (STX) and its analogs, the paralytic shellfish toxins (PSTs), are a
      group of potent neurotoxins well known for their role in acute paralytic
      poisoning by preventing the generation of action potentials in neuronal cells.
      They are found in both marine and freshwater environments globally and although
      acute exposure from the former has previously received more attention, low dose
      extended exposure from both sources is possible and to date has not been
      investigated. Given the known role of cellular electrical activity in
      neurodevelopment this pattern of exposure may be a significant public health
      concern. Additionally, the presence of PSTs is likely to be an ongoing and
      possibly increasing problem in the future. This review examines the
      neurodevelopmental toxicity of STX, the risk of extended or repeated exposure to
      doses with neurodevelopmental effects, the potential implications of this
      exposure and briefly, the steps taken and difficulties faced in preventing
      exposure.

PMID- 27716537
TI  - Colorectal cancer incidence in 5 Asian countries by subsite: An analysis of
      Cancer Incidence in Five Continents (1998-2007).
AB  - Colorectal cancer is the fourth most common cancer in Asia. However, the trends
      in colorectal cancer incidence by subsite have not been analyzed across Asian
      countries. We used the most recent, high quality data from 6 cancer registries
      for two 5-year periods, 1998-2002 and 2003-2007, from Cancer Incidence in Five
      Continents to estimate colorectal cancer incidence by subsite in 5 Asian
      countries. Cases with overlapping lesions or otherwise unspecified colon cancer
      were re-distributed as proximal or distal colon cancer. Age-standardized
      incidence rates (ASRs) per 100,000 population and incidence rate ratios from 1998
      to 2002 to 2003-2007 were calculated for each subsite. For 2003-2007, men in
      Miyagi, Japan, had the highest ASR for cancer in the proximal colon, distal colon
      and rectum. Men of Jewish ancestry in Israel had a high ASR for proximal and
      distal colon cancer, but the lowest ASR for rectal cancer. The proportion of
      rectal cancer was highest among Korean men (51.39%) and lowest among Israeli
      women (26.6%). From 1998-2002 to 2003-2007, rectal cancer incidence did not
      significantly change in most registries, except for men in Miyagi, Japan, and
      both sexes in Korea. However, during the same period cancer incidence in the
      proximal and distal colon increased in most registries. In conclusion, there was
      substantial variation in subsite distributions of colorectal cancer in Asian
      registries and increases in overall incidence of colorectal cancer could be
      attributed to increases in colon cancer.

PMID- 27716536
TI  - An in vivo assay performed using multiple biomarkers related to testosterone
      synthesis and conversion for assessing the androgenic potency of refuse leachate.
AB  - Refuse leachate is likely an important source of androgens. However, common in
      vitro bioassays underestimate the potential androgenic activity of leachate,
      owing to non-receptor-mediated mechanisms that modify the balance of sex hormones
      and promote the accumulation of endogenous androgens. This study aimed to develop
      an in vivo assay by using multiple biomarkers related to testosterone synthesis
      and conversion for assessing the potential androgenic activity of refuse leachate
      sampled from a municipal solid waste treatment plant in Qingdao, China. The
      results indicated that exposure to leachate increased the levels of testosterone
      and luteinizing hormone, but decreased those of 17beta-estradiol in both male and
      female goldfish (Carassius auratus), suggesting a potential androgenic activity.
      Further, Leydig cell hyperplasia and decreased gonadal P450 aromatase mRNA levels
      were observed; these alterations might promote the biosynthesis of testosterone
      and hinder the conversion of testosterone to 17beta-estradiol, which in turn
      enhance testosterone accumulation. Exposure to leachate also resulted in
      reproductive impairments, including decreased gonadosomatic index and plasma
      vitellogenin levels of female goldfish, as well as decreased testicular enzyme
      activities in male goldfish. The integrated use of biochemical, molecular, and
      histological markers not only improved our understanding of the androgenic
      effects of leachate but also verified the reliability and validity of the
      results. Therefore, the in vivo bioassay described in this study might allow the
      investigation of the androgenic effects of other complex contaminant mixtures in
      the future.

PMID- 27716535
TI  - Brain and cognitive functions in two groups of naive HIV patients selected for a
      different plan of antiretroviral therapy: A qEEG study.
AB  - OBJECTIVE: Cortical sources of electroencephalographic (EEG) rhythms were
      investigated in two sub-populations of naive HIV subjects, grouped based on
      clinical criteria to receive different combination anti-retroviral therapies
      (cARTs). These EEG sources were hypothesized to reflect beneficial effects of
      both regimes. METHODS: Eyes-closed resting state EEG data were collected in 19
      (Group A) and 39 (Group B) naive HIV subjects at baseline (i.e. pre-treatment;
      T0) and after 5months of cART (T5). Compared with the Group A, the Group B was
      characterized by slightly worse serological parameters and higher cardiovascular
      risk. At T0, mean viral load (VL) and CD4 count were 87,694copies/ml and
      435cells/MUl in the Group A and 187,370copies/ml and 331cells/MUl in the Group B.
      The EEG data were also collected in 50 matched control HIV-negative subjects.
      Cortical EEG sources were assessed by LORETA software. RESULTS: Compared to the
      Control Group, the HIV Groups showed lower alpha (8-12Hz) source activity at T0
      while the Group B also exhibited higher delta source activity. The treatment
      partially normalized alpha and delta source activity in the Group A and B,
      respectively, in association with improved VL, CD4, and cognitive functions.
      CONCLUSIONS: Different cART regimens induced diverse beneficial effects in delta
      or alpha source activity in the two naive HIV Groups. SIGNIFICANCE: These sources
      might unveil different neurophysiological effects of diverse cART on brain
      function in naive HIV Groups as a function of clinical status and/or therapeutic
      compounds.

PMID- 27716538
TI  - Molecular dynamics of the honey bee toxin tertiapin binding to Kir3.2.
AB  - Tertiapin (TPN), a short peptide isolated from the venom of the honey bee, is a
      potent and selective blocker of the inward rectifier K+ (Kir) channel Kir3.2.
      Here we examine in atomic detail the binding mode of TPN to Kir3.2 using
      molecular dynamics, and deduce the key residue in Kir3.2 responsible for TPN
      selectivity. The binding of TPN to Kir3.2 is stable when the side chain of either
      Lys16 (TPNK16-Kir3.2) or Lys17 (TPNK17-Kir3.2) of the toxin protrudes into the
      channel pore. However, the binding affinity calculated from only TPNK17-Kir3.2
      and not TPNK16-Kir3.2 is consistent with experiment, suggesting that Lys17 is the
      most plausible pore-blocking residue. The alanine mutation of Kir3.2-Glu127,
      which is not present in TPN-resistant channels, reduces the inhibitory ability of
      TPN by over 50 fold in TPNK17-Kir3.2, indicating that Kir3.2-Glu127 is important
      for the selectivity of TPN.

PMID- 27716539
TI  - Rorschach Performance Assessment System (R-PAS) and vulnerability to stress: A
      preliminary study on electrodermal activity during stress.
AB  - This study investigated the predictive validity of the ten Rorschach Performance
      Assessment System (R-PAS) variables from the Stress and Distress domain, by
      testing whether they predicted increased sympathetic reactivity to a mild,
      laboratory-induced stress, occurred one week after Rorschach administration. A
      relatively small student sample (N=52) contributed to this research: During a
      first meeting (T1) participants were administered the Rorschach task according to
      R-PAS guidelines; about one week later (T2) their electrodermal activity (EDA)
      was recorded during exposure to a mild laboratory stress-inducing task. Based on
      literature indicating that exposure to stress tends to increase physiological
      vulnerability/reactivity to stressful situations, we anticipated that Stress and
      Distress R-PAS variables measured at T1 would positively correlate with increased
      sympathetic reactivity to stress at T2, as indicated by greater EDA changes from
      baseline to stress and recovery. Results partially confirmed our hypotheses: (a)
      the mean of and (b) the majority of the Stress and Distress R-PAS variables were
      significantly correlated, in the expected direction, with medium and medium to
      large effect sizes.

PMID- 27716540
TI  - Immediate postpartum mood assessment and postpartum depressive symptoms.
AB  - BACKGROUND: Negative affect (NA) and positive affect (PA) in the early postpartum
      period have been associated with postpartum depressive symptoms, but the exact
      relationship is not well understood. This study aimed to determine if NA and PA
      in the immediate postpartum period predicted postpartum depressive symptoms over
      and above well-established predictors (previous trauma, history of depression).
      METHODS: Participants were prospectively recruited from a Mother-Baby Unit at a
      large Midwestern academic medical center in the United States from April 2011 to
      April 2014. Participants (N=526) completed the Daily Experiences Questionnaire
      (DEQ), a self-report measure which assessed NA and PA, within three days post
      delivery. Participants then reported their depressive symptoms at two weeks
      (n=364) and twelve weeks postpartum (n=271). RESULTS: Hierarchical regression
      analyses indicated that low PA and high NA after birth significantly predicted
      depressive symptoms early (at 2 weeks) and later (at 12 weeks) in the postpartum
      period, over and above previous traumatic experiences and history of depression.
      LIMITATIONS: The sample was relatively homogenous, and data were from self-report
      instruments. CONCLUSIONS: The current study found NA and PA in the days
      immediately after birth predicted depressive symptoms at multiple time points in
      the postpartum period. Because the perinatal period places women at a higher risk
      for depressive symptomatology, prevention and early intervention are critical.
      Measuring affect in hospitals immediately after birth may provide a more
      normalized set of items that is predictive of later depression, which will allow
      physicians to identify those at highest risk for developing depressive symptoms.

PMID- 27716541
TI  - Acquisition of CS-US contingencies during Pavlovian fear conditioning and
      extinction in social anxiety disorder and posttraumatic stress disorder.
AB  - BACKGROUND: Fear-based disorders, like social anxiety disorder (SAD) and
      posttraumatic stress disorder (PTSD), are characterized by an exaggerated fear
      response and avoidance to trigger cues, suggesting a transdiagnostic mechanism of
      psychopathology. Current theories suggest that abnormalities in conditioned fear
      is a primary contributor to the pathophysiology of these disorders. The primary
      goal of this study was to compare acquisition of conditioned stimulus (CS) and
      aversive unconditioned stimulus (US) contingencies during fear learning and
      extinction in individuals with SAD and PTSD. METHODS: In a standard Pavlovian
      fear conditioning-extinction paradigm we measured subjective US expectancy
      ratings to different CSs in patients with SAD (n=16) compared to patients with
      PTSD (n=13) and healthy controls (n=15) RESULTS: Both patient groups (SAD, PTSD)
      acquired differential conditioning between a CS that predicted US (CS+) and a CS
      that never predicted the US (CS-), however, both groups reported an increased
      expectancy that the US would occur following the CS-. Additionally, the PTSD
      group overestimated that the US would occur in general. Neither patient group
      showed evidence of successful extinction of the CS+-US contingency nor
      differentiated their expectation of US occurrence between the CS+ and CS- during
      extinction learning. LIMITATIONS: Group sample sizes were small and we did not
      include a trauma-exposed group without PTSD CONCLUSIONS: Both SAD and PTSD
      generalize expectations of an aversive outcome across CSs, even when a CS never
      signals an aversive outcome and PTSD may tend to over-expect threat. Fear
      learning and extinction abnormalities may be a core feature underlying shared
      symptoms across fear-based disorders.

PMID- 27716543
TI  - Deficiency in memory B cell compartment in a patient with infertility and
      recurrent pregnancy losses.
AB  - Alterations in normal balance of B cell subsets have been reported in various
      rheumatic diseases. In this study, we report a woman with a history of recurrent
      pregnancy losses (RPL) and infertility who had low levels of memory B cells. A 35
      year-old woman with a history of RPL and infertility was demonstrated to have
      increased peripheral blood CD19+ B cells with persistently low levels of memory B
      cell subsets. Prior to the frozen donor egg transfer cycle, prednisone and
      intravenous immunoglobulin G (IVIg) treatment was initiated and patient achieved
      dichorionic diamniotic twin pregnancies. During pregnancy, proportion (%) of
      switched memory B cells CD27+IgD- increased, while percent of total CD19+ B cells
      and CD27-IgD+ naive B cells were gradually decreased with a high dose IVIg
      treatment. She developed cervical incompetence at 20 weeks of gestation, received
      a Cesarean section at 32 weeks of gestation due to preterm labor, and delivered
      twin babies. B cell subset abnormalities may be associated with infertility, RPL
      and preterm labor, and further investigation is needed.

PMID- 27716544
TI  - Amygdala-based intrinsic functional connectivity and anxiety disorders in
      adolescents and young adults.
AB  - Anxiety disorders (AD) are the most prevalent group of psychiatric disorders in
      adolescents and young adults. Nevertheless, the pathophysiology of anxiety
      disorders is still poorly understood. This study investigated differences in the
      functional connectivity of intrinsic amygdala-based networks of participants with
      and without AD. Resting state fMRI data were obtained from 18 participants with
      an AD and 19 healthy comparison individuals. Psychiatric diagnosis was assessed
      using standardized structured interviews. The comparison between groups was
      carried out using functional connectivity maps from six seed regions defined
      using probabilistic maps bilaterally within the amygdala (basolateral,
      superficial and centromedial amygdala). We found significant between-group
      differences in five clusters, which showed aberrant functional connectivity with
      the left basolateral amygdala: right precentral gyrus, right cingulate gyrus,
      bilateral precuneus, and right superior frontal gyrus in subjects with AD as
      compared with the comparison subjects. For the comparison subjects, the
      correlations between the amygdala and the five clusters were either non
      significant, or negative. The present study suggests there is an intrinsic
      disruption in the communication between left basolateral amygdala and a network
      of brain regions involved with emotion regulation, and with the default mode
      network in adolescents and young adults with anxiety disorders.

PMID- 27716542
TI  - Resting-state functional connectivity of the amygdala and longitudinal changes in
      depression severity in adolescent depression.
AB  - BACKGROUND: The incidence of major depressive disorder (MDD) rises during
      adolescence, yet the neural mechanisms of MDD during this key developmental
      period are unclear. Altered amygdala resting-state functional connectivity (RSFC)
      has been associated with both adolescent and adult MDD, as well as symptom
      improvement in response to treatment in adults. However, no study to date has
      examined whether amygdala RSFC is associated with changes in depressive symptom
      severity in adolescents. METHOD: We examined group differences in amygdala RSFC
      between medication-naive depressed adolescents (N=48) and well-matched healthy
      controls (N=53) cross-sectionally. We then longitudinally examined whether
      baseline amygdala RSFC was associated with change in depression symptoms three
      months later in a subset of the MDD group (N=24). RESULTS: Compared to healthy
      controls, depressed adolescents showed reduced amygdala-based RSFC with the
      dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex
      (VMPFC). Within the depressed group, more positive baseline RSFC between the
      amygdala and insulae was associated with greater reduction in depression symptoms
      three months later. LIMITATIONS: Only a subset of depressed participants was
      assessed at follow-up and treatment type and delivery were not standardized.
      CONCLUSIONS: Adolescent depression may be characterized by dysfunction of
      frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional
      regulation, whereas those circuits (amygdala-insula) subserving affective
      integration may index changes in depression symptom severity and may therefore
      potentially serve as a candidate biomarker for treatment response. Furthermore,
      these results suggest that the biomarkers of MDD presence are distinct from those
      associated with change in depression symptoms over time.

PMID- 27716546
TI  - Effectiveness of light-reflecting devices: A systematic reanalysis of animal
      vehicle collision data.
AB  - Every year, approximately 500 human fatalities occur due to animal-vehicle
      collisions in the United States and Europe. Especially heavy-bodied animals
      affect road safety. For more than 50 years, light-reflecting devices such as
      wildlife warning reflectors have been employed to alert animals to traffic when
      crossing roads during twilight and night. Numerous studies addressed the
      effectiveness of light-reflecting devices in reducing collisions with animals in
      past decades, but yielded contradictory results. In this study, we conducted a
      systematic literature review to investigate whether light-reflecting devices
      contribute to an effective prevention of animal-vehicle collisions. We reviewed
      53 references and reanalyzed original data of animal-vehicle collisions with meta
      analytical methods. We calculated an effect size based on the annual number of
      animal-vehicle collisions per kilometer of road to compare segments with and
      without the installation of light-reflecting devices for 185 roads in Europe and
      North America. Our results indicate that light-reflecting devices did not
      significantly reduce the number of animal-vehicle collisions. However, we
      observed considerable differences of effect sizes with respect to study duration,
      study design, and country. Our results suggest that length of the road segment
      studied, study duration, study design and public attitude (preconception) to the
      functioning of devices may affect whether the documented number of animal-vehicle
      collisions in- or decrease and might in turn influence whether results obtained
      were published.

PMID- 27716545
TI  - Youth with substance abuse histories exhibit dysfunctional representation of
      expected value during a passive avoidance task.
AB  - Individuals with substance abuse (SA) histories show impairment in the
      computations necessary for decision-making, including expected value (EV) and
      prediction error (PE). Neuroimaging findings, however, have been inconsistent.
      Sixteen youth with (SApositive) and 29 youth without (SAnegative) substance abuse
      histories completed a passive avoidance task while undergoing functional MRI. The
      groups did not significantly differ on age, gender composition or IQ. Behavioral
      results indicated that SApositive youth showed significantly less learning than
      SAnegative youth over the task. SApositive youth show problems representing EV
      information when attempting to avoid sub-optimal choices in bilateral inferior
      frontal gyrus and striatum. Furthermore, SApositive youth showed a significantly
      increased differential response to reward versus punishment feedback modulated by
      PE in posterior cingulate cortex relative to SAnegative youth. Disrupted decision
      making is likely to exacerbate SA as a failure to represent EV during the
      avoidance of sub-optimal choices is likely to increase the likelihood of SA. With
      respect to the representation of PE, future work will be needed to clarify the
      impact of different substances on the neural systems underpinning PE
      representation. Moreover, interaction of age/development and substance abuse on
      PE signaling will need to be explored.

PMID- 27716547
TI  - How do they feel? Patients' perspectives on draping and dignity in a
      physiotherapy outpatient setting: A pilot study.
AB  - BACKGROUND: Research to date has focused on dignity within the hospital rather
      than outpatient settings which is likely to raise different issues from the
      patients' perspective. PURPOSE: To investigate patients' views relating to
      draping and dignity and their choice of dressing options in the physiotherapy
      outpatient setting. METHOD: A custom-designed questionnaire was developed
      including feedback from a focus group of 10 individuals attending a physiotherapy
      outpatient clinic. The final version of the questionnaire comprised 14 items
      covering issues regarding privacy, draping, respect and communication. Patients
      attending outpatient physiotherapy for musculoskeletal treatment were invited to
      complete the questionnaire which was administered over a period of seven weeks.
      RESULTS: Of the 31 respondents completing the questionnaire (n = 23 females, n =
      8 males), the majority of males (87.5% n = 7) felt very confident removing their
      clothing whereas 26.1% of females (n = 6) reported feeling confident when asked
      to remove their clothing. Female respondents also considered the gender of their
      physiotherapist (87% n = 21) as well as physical privacy (73.9% n = 17) to be
      important factors related to patient dignity. All male respondents (100%)
      expressed a preference for exposing the bare back whereas the females expressed
      mixed dressing preferences. The preferred dressing option for the lower body for
      both males and female respondent was sport shorts (87.5% n = 7; 81.8% n = 18
      respectively). CONCLUSION: The patients' perspective of dignity and draping in a
      physiotherapy musculoskeletal settings is seen in terms of physical space, the
      provision of a range of draping options in conjunction with clear communication
      by their physiotherapist.

PMID- 27716549
TI  - Associations between quantitative measures of women's empowerment and access to
      care and health status for mothers and their children: A systematic review of
      evidence from the developing world.
AB  - Research on the association between women's empowerment and maternal and child
      health has rapidly expanded. However, questions concerning the measurement and
      aggregation of quantitative indicators of women's empowerment and their
      associations with measures of maternal and child health status and healthcare
      utilization remain unanswered. Major challenges include complexity in measuring
      progress in several dimensions and the situational, context dependent nature of
      the empowerment process as it relates to improvements in maternal and child
      health status and maternal care seeking behaviors. This systematic literature
      review summarizes recent evidence from the developing world regarding the role
      women's empowerment plays as a social determinant of maternal and child health
      outcomes. A search of quantitative evidence previously reported in the economic,
      socio-demographic and public health literature finds 67 eligible studies that
      report on direct indicators of women's empowerment and their association with
      indicators capturing maternal and child health outcomes. Statistically
      significant associations were found between women's empowerment and maternal and
      child health outcomes such as antenatal care, skilled attendance at birth,
      contraceptive use, child mortality, full vaccination, nutritional status and
      exposure to violence. Although associations differ in magnitude and direction,
      the studies reviewed generally support the hypothesis that women's empowerment is
      significantly and positively associated with maternal and child health outcomes.
      While major challenges remain regarding comparability between studies and lack of
      direct indicators in key dimensions of empowerment, these results suggest that
      policy makers and practitioners must consider women's empowerment as a viable
      strategy to improve maternal and child health, but also as a merit in itself.
      Recommendations include collection of indicators on psychological, legal and
      political dimensions of women's empowerment and development of a comprehensive
      conceptual framework that can guide research and policy making.

PMID- 27716550
TI  - The importance of a correct methodological approach for the arrhythmic risk
      evaluation in beta thalassemia major patients.

PMID- 27716548
TI  - The use of specialty training to retain doctors in Malawi: A discrete choice
      experiment.
AB  - Emigration has contributed to a shortage of doctors in many sub-Saharan African
      countries. Specialty training is highly valued by doctors and a potential tool
      for retention. Yet not all types of training may be valued equally. In the first
      study to examine preferences for postgraduate training in depth, we carried out a
      discrete choice experiment as part of a cross-sectional survey of all Malawian
      doctors within seven years of graduation and not yet in specialty training. Over
      August 2012 to March 2013, 148 doctors took part out of 153 eligible in Malawi.
      Despite evidence that specialty training is highly sought after, Malawian junior
      doctors would not accept all types of training. Doctors preferred timely training
      outside of Malawi in core specialties (internal medicine, general surgery,
      paediatrics, obstetrics & gynaecology). Specialty preferences are particularly
      strong, with most junior doctors requiring nearly double their monthly salary to
      accept training all in Malawi and over six-fold to accept training in
      ophthalmology (representing a bundle of unpopular but priority specialties). In
      contrast, the location of work before training did not significantly influence
      most doctors' choices when guaranteed specialty training. Using a latent class
      model, we identified four subgroups of junior doctors with distinct preferences.
      Policy simulations showed that these preferences could be leveraged by
      policymakers to improve retention in exchange for guaranteed specialty training,
      however incentivising the uptake of training in priority specialties will only be
      effective in those with more flexible preferences. These results indicate that
      indiscriminate expansion of postgraduate training to slow emigration of doctors
      from sub-Saharan African countries may not be effective unless doctors'
      preferences are taken into account.

PMID- 27716551
TI  - Disc movement sign: A clue to malpositioned Amplatzer cardiac plug impinging on
      mitral leaflet.

PMID- 27716552
TI  - Venlafaxine and takotsubo syndrome: Can we learn more from published patient
      cases?

PMID- 27716553
TI  - Fukutin mutations in Fukuyama congenital muscular dystrophy do not cause
      noncompaction.

PMID- 27716554
TI  - Efficacy and safety of novel anticoagulants versus vitamin K antagonists in
      patients with mild and moderate to severe renal insufficiency: Focus on apixaban.
AB  - The high risk of both stroke and major bleeding in atrial fibrillation (AF)
      patients with chronic kidney disease (CKD) defines an important population for
      whom the assessment of the balance between the risk of ischemic stroke and of
      bleeding is essential. The use of novel oral anticoagulants (NOACs) may be a
      viable option in this population due to their greater net clinical benefit than
      warfarin, as demonstrated by the results of the clinical phase III trials. NOACs
      have been found to have a greater net clinical benefit than warfarin in patients
      at high risk of either stroke (CHADS2>=1 or CHA2DS2-VASc score>=2) or bleeding
      (HAS-BLED>=3). Noteworthy, it has been found also a positive net clinical benefit
      with apixaban and dabigatran 110mg BID in patients with CHADS2 score=0 and HAS
      BLED score>=3. At CHA2DS2-VASc score=1, apixaban and both doses of dabigatran
      were superior to warfarin in terms of the net clinical benefit. Available
      scientific evidence might help in clinical decision-making regarding the use of
      NOACs in patients with CKD who are at high risk for both stroke and bleeding.
      Overall, current findings provide a rationale for the choice of apixaban or
      rivaroxaban over dabigatran in patients with AF and stage III CKD. Out of the
      NOACs, only apixaban has been recently approved for the use in patients with end
      stage renal dysfunction on hemodialysis (the recommended dose of 5mg twice daily
      should be halved in patients with body weight of <=60kg and or age>=80years).

PMID- 27716555
TI  - Long-term outcomes of catheter ablation of atrial fibrillation post-cardiac valve
      replacement.
AB  - OBJECTIVE: The long-term outcomes of catheter ablation of atrial fibrillation
      (AF) developing post-cardiac valve replacement (VR) remain undefined. METHODS AND
      RESULTS: Eighty-nine post-VR patients with AF (44% longstanding persistent AF,
      LSP-AF) were enrolled. Cumulative success rate of circumferential pulmonary vein
      ablation (CPVA for paroxysmal AF) and bidirectional block of lines and
      disappearance of complex fractionated atrial electrograms (CFAEs for persistent
      and LSP-AF) as index and repeat procedural endpoints reached 57% (mean, 1.3
      procedures) during the first year, and dropped to 42% at median follow-up of
      40months (range, 24-70months) for multiple procedures (mean, 1.6+/-0.9 [1-5]);
      incidence of procedural complications was similar to that of conventional
      procedures. In multivariate analysis, larger right atrium (RA, 9.40 [2.64-33.36];
      P=0.001) and rheumatic valvular disease etiology (OR, 5.49 [95% CI, 1.26-23.96];
      P=0.023) were significant independent predictors of recurrent atrial
      tachyarrhythmia (ATa); in contrast, long-term freedom from ATa was comparable
      between single and double valve replacement groups (42.1% vs. 43.7%, P=0.880), or
      mechanical and bioprosthetic valves groups (41.7% vs. 50.0%, P=0.620).
      CONCLUSION: In this single-center prospective study, treatment of post-VR AF with
      commonly used ablation strategies including CPVA and linear and CFAE ablation had
      limited long-term success, with ATa recurrence risk appearing higher in the
      setting of RA enlargement and rheumatic valvular disease and unrelated to valves
      characteristics.

PMID- 27716556
TI  - A retrospective analysis of laser endartherectomy assisted balloon angioplasty
      for popliteal and infrapopliteal peripheral arterial disease.
AB  - OBJECTIVES: To describe our single center experience with the use of laser
      endartherectomy assisted balloon angioplasty in popliteal and infrapopliteal
      arterial disease. BACKGROUND: Peripheral arterial disease (PAD) carries
      significant morbidity to patients. Some patients may have multiple comorbid
      conditions potentially limiting therapeutic options for PAD. Endovascular
      interventions are aimed at decreasing arterial disease symptoms, improve wound
      healing and ultimately limb salvage. There is limited data on below the knee PAD
      and simultaneous laser endartherectomy use in this anatomic location. METHODS:
      The cohort comprised 41 patients that underwent laser assisted balloon
      angioplasty from 2010 to 2013. All patients had popliteal and infrapopliteal
      arterial disease. Outcomes evaluated were limb salvage and symptom relief
      12months following the procedure. A comparison between the patients that
      underwent amputation and those with limb salvage was also performed. RESULTS: All
      the patients had TASC II (Trans Atlantic Inter-Society Consensus) type D lesions.
      Most patients reported persistent PAD symptoms by six months, with 17% remaining
      symptom free by 12months. Affected limb salvage was 69%. Five patients (12%) died
      and one third of the patients had a new peripheral angiogram. In the repeat
      angiogram, most patients showed initial target vessel occlusion. No statistically
      significant differences were found between the patients that preserved their limb
      to those who underwent amputation. CONCLUSIONS: Laser assisted balloon
      angioplasty use for complex popliteal and infrapopliteal arterial disease is a
      therapeutic option when limb salvage is the goal. Despite this, symptom
      recurrence and the need for repeated angiography continue to be high.

PMID- 27716557
TI  - Circulating level of pigment epithelium-derived factor is associated with
      vascular function and structure: A cross-sectional study.
AB  - BACKGROUND: Pigment epithelium-derived factor (PEDF) is a glycoprotein that
      belongs to the superfamily of serine protease inhibitors. It is thought that PEDF
      plays a protective role against atherosclerosis. Clinical studies have shown that
      serum levels of PEDF are increased in subjects with cardiovascular risk factors.
      The role of PEDF in cardiovascular disease is still controversial. The purpose of
      this study was to evaluate the associations between serum levels of PEDF and
      vascular function and structure. METHODS: We measured serum levels of PEDF,
      assessed vascular function by measurements of flow-mediated vasodilation (FMD)
      and nitroglycerine-induced vasodilation in the brachial artery, and measured
      brachial artery intima-media thickness (IMT) in 150 subjects who underwent health
      examinations. RESULTS AND CONCLUSIONS: Univariate regression analysis revealed
      that serum level of PEDF was significantly correlated with body mass index, high
      density lipoprotein cholesterol, glucose, FMD, nitroglycerine-induced
      vasodilation, and brachial artery IMT. Multivariate analysis revealed that serum
      levels of PEDF remained an independent predictor of nitroglycerine-induced
      vasodilation (beta=-0.20, P=0.02) and brachial artery IMT (beta=0.14, P=0.03)
      after adjustment of cardiovascular risk factors, while serum level of PEDF was
      not associated with FMD (beta=-0.02, P=0.79). These findings suggest that PEDF
      may be a factor directly associated with atherosclerosis. The serum level of PEDF
      may be a new biochemical marker of atherosclerosis.

PMID- 27716558
TI  - Early pre-occlusive bilateral renal artery stenosis after renal denervation.

PMID- 27716559
TI  - Patients with calcific aortic stenosis exhibit systemic molecular evidence of
      ischemia, enhanced coagulation, oxidative stress and impaired cholesterol
      transport.
AB  - BACKGROUND: The most common valve diseases are calcific aortic stenosis (AS) and
      aortic regurgitation (AR). The former is characterized by thickening of valve
      leaflets followed by progressive calcification, which produces progressive aortic
      valve (AV) narrowing, increased pressure afterload on the left ventricle (LV) and
      subsequent LV hypertrophy. On the other hand, AR is due to malcoaptation of the
      valve leaflets with resultant diastolic reflux of blood from aorta back to the LV
      producing volume and pressure overload and progressive LV dilatation. In order to
      isolate the molecular mechanisms taking place during AS, we have used an
      integrated "-omic" approach to compare plasma samples from AS and from AR
      patients used as controls. The final purpose of this work is to find molecular
      changes in response to the calcification of the AV, diminishing the effects of
      the AV dysfunction. METHODS AND RESULTS: Using two-dimensional difference gel
      electrophoresis (2D-DIGE) and gas chromatography coupled to mass spectrometry (GC
      MS) in a cohort of 6 subjects, we have found differences in 24 protein spots and
      19 metabolites, respectively. Among them, 7 proteins and 3 metabolites have been
      verificated by orthogonal techniques (SRM or turbidimetry): fibrinogen beta and
      gamma chain, vitronectin, apolipoprotein C-II, antithrombin III, haptoglobin,
      succinic acid, pyroglutamic acid and alanine. Classification according to their
      main function showed alterations related to coagulation, inflammation, oxidative
      stress, response to ischemia and lipid metabolism, defining 4 different molecular
      panels that characterize AS with high specificity and sensitivity. CONCLUSION:
      These results may facilitate management of these patients by making faster
      diagnostics of the disease and better understand these pathways for regulating
      its progression.

PMID- 27716560
TI  - The perception and acceptability of pre-slaughter and post-slaughter stunning for
      Halal production: The views of UK Islamic scholars and Halal consumers.
AB  - The importance of religious slaughter from economic, emotive and ethical
      viewpoints is significant. There are apparent economic benefits associated with
      trading in meats slaughtered according to religious traditions. Some religious
      authorities insist on the slaughter of animals without stunning, but this,
      according to many researchers, compromises animal welfare. We conducted a survey
      of Islamic scholars and Halal consumers, 66 scholars from 55 organisations and
      314 consumers from 54 UK cities/towns were surveyed. Forty-nine scholars were
      interviewed through pre-arranged meetings, 17 surveyed online whilst all 314
      consumers were either surveyed online or through the remote completion of copies
      of the questionnaire. Most of the scholars (>95%) (CI 86.9 to 98.4%) agreed that
      if an animal is stunned and then slaughtered by a Muslim and the method of
      stunning does not result in death, cause physical injury or obstruct bleed-out,
      the meat would be Halal and 53% (CI 47 to 58%) consumers also thought such meat
      would be Halal.

PMID- 27716561
TI  - Multiple antibiotic resistance genes distribution in ten large-scale membrane
      bioreactors for municipal wastewater treatment.
AB  - Wastewater treatment plants are thought to be potential reservoirs of antibiotic
      resistance genes. In this study, GeoChip was used for analyzing multiple
      antibiotic resistance genes, including four multidrug efflux system gene groups
      and three beta-lactamase genes in ten large-scale membrane bioreactors (MBRs) for
      municipal wastewater treatment. Results revealed that the diversity of antibiotic
      genes varied a lot among MBRs, but about 40% common antibiotic resistance genes
      were existent. The average signal intensity of each antibiotic resistance group
      was similar among MBRs, nevertheless the total abundance of each group varied
      remarkably and the dominant resistance gene groups were different in individual
      MBR. The antibiotic resistance genes majorly derived from Proteobacteria and
      Actinobacteria. Further study indicated that TN, TP and COD of influent,
      temperature and conductivity of mixed liquor were significant (P<0.05) correlated
      to the multiple antibiotic resistance genes distribution in MBRs.

PMID- 27716562
TI  - The excellent performance of nest-like oxygen-deficient Cu1.5Mn1.5O4 applied in
      activated carbon air-cathode microbial fuel cell.
AB  - This study investigated the performance of nano spinel nest-like oxygen-deficient
      Cu1.5Mn1.5O4 doping activated carbon (AC) as air cathode in microbial fuel cell
      (MFC). The Cu1.5Mn1.5O4 was synthesized via hydrothermal method and subsequent
      annealed. The maximum power density (MPD) of MFC with oxygen-deficient
      Cu1.5Mn1.5O4 modified cathode was 1928+/-18mWm-2, which was 1.53 times higher
      than the bare cathode. The electrochemical studies showed that Cu1.5Mn1.5O4
      doping AC exhibited higher kinetic activity and lower resistance. The mechanism
      of oxygen reduction for the catalyst was a four electron pathway. The oxygen
      deficient of Cu1.5Mn1.5O4 played an important role in catalytic activity. So
      Cu1.5Mn1.5O4 would be an excellent promising catalyst for ORR in MFC.

PMID- 27716563
TI  - Interaction between common antibiotics and a Shewanella strain isolated from an
      enhanced biological phosphorus removal activated sludge system.
AB  - With increasing production and consumption, more antibiotics are discharged into
      wastewater treatment plants and generally cannot be sufficiently removed. Because
      of the complexities of biological treatment processes, the fates of antibiotics
      and their effects on microorganisms, particularly those involved in the
      phosphorus removal system, are still unclear. Here, a Shewanella strain was
      isolated from an enhanced biological phosphorus removal (EBPR) system and was
      found to have the ability to remove phosphorus (P) and chemical oxygen demand
      (CODcr). Antibiotics affected the Shewanella strain through metabolism of the
      three main intracellular polymers, altering the ability of the strain to remove P
      and CODcr. These effects varied with the structure and concentration of the
      antibiotics. The Shewanella strain removed cefalexin and amoxicillin by
      degradation or adsorption, producing 2-hydroxy-3-phenyl pyrazine from cefalexin.
      This study enabled the recognition of the effect and removal of antibiotics
      during wastewater treatment.

PMID- 27716564
TI  - Efficient conversion of pretreated brewer's spent grain and wheat bran by
      submerged cultivation of Hericium erinaceus.
AB  - Brewer's spent grain (BSG) and wheat bran (WB) are industrial byproducts that
      accumulate in millions of tons per year and are typically applied as animal feed.
      Since both byproducts show a great potential as substrates for fermentation, the
      approach developed in this study consists of utilizing these lignocellulosic
      byproducts for biomass production of the medicinal fungus Hericium erinaceus
      through submerged cultivation. To increase the biological efficiency of the
      bioconversion, acidic pretreatment was applied yielding a bioconversion of 38.6%
      for pretreated BSG and 34.8% for pretreated WB. This study shows that the
      complete degradation of (hemi)cellulose into monosaccharides was not required for
      an efficient bioconversion. The produced fungal biomass was applied in a second
      fermentation step to induce the secondary metabolite erinacine C production.
      Thus, biomass was produced as a functional food ingredient with erinacine C
      contents of 174.8mg/g for BSG and 99.3mg/g for WB based bioconversions.

PMID- 27716565
TI  - Performance and microbial community of a sequencing batch biofilm reactor
      treating synthetic mariculture wastewater under long-term exposure to
      norfloxacin.
AB  - The performance and microbial community of a sequencing batch biofilm reactor
      (SBBR) treating synthetic mariculture wastewater were evaluated under long-term
      exposure to norfloxacin (NFX) due to the overuse of antibiotics during the
      mariculture. The COD and NH4+-N removals had no distinct change at 0-6mgL-1 NFX
      and were inhibited at 6-35mgL-1 NFX. The specific oxygen uptake rate (SOUR),
      specific ammonium oxidation rate (SAOR), specific nitrite oxidation rate (SNOR)
      and specific nitrate reduction rate (SNRR) of the biofilm kept a decreasing
      tendency with the increase of NFX concentration from 0 to 35mgL-1. The presence
      of NFX promoted the microorganisms to secrete more extracellular polymeric
      substances (EPS) and affected the chemical compositions of EPS. The microbial
      richness and diversity showed some obvious variations at different NFX
      concentrations. The present results demonstrated that NFX inhibited the SBBR
      performance and should decrease the NFX dosage in the mariculture.

PMID- 27716566
TI  - Material and microbial changes during corn stalk silage and their effects on
      methane fermentation.
AB  - Silage efficiency is crucial for corn stalk storage in methane production. This
      study investigated characteristics of dynamic changes in materials and microbes
      during the silage process of corn stalks from the initial to stable state. We
      conducted laboratory-scale study of different silage corn stalks, and optimized
      silage time (0, 2, 5, 10, 20, and 30days) for methane production and the
      endogenous microbial community. The volatile fatty acid concentration increased
      to 3.00g/L on Day 10 from 0.42g/L on Day 0, and the pH remained below 4.20 from
      5.80. The lactic acid concentration (44%) on Day 10 lowered the pH and inhibited
      the methane yield, which gradually decreased from 229mL/g TS at the initial state
      (Day 0, 2) to 207mL/g TS at the stable state (Day 10, 20, 30). Methanosaeta was
      the predominant archaea in both fresh and silage stalks; however, richness
      decreased from 14.11% to 4.75%.

PMID- 27716567
TI  - Growth in very preterm children: Head growth after discharge is the best
      independent predictor for cognitive outcome.
AB  - BACKGROUND: The contribution of growth parameters to the cognitive outcome of
      very low birth weight (VLBW)/very preterm (VP) infants is difficult to
      disentangle from other preterm-birth related factors. AIMS: We hypothesized that
      long-term cognitive and motor outcome of VLBW/VP infants is most strongly
      associated with growth in head circumference after hospital discharge. STUDY
      DESIGN: Single-centre prospective longitudinal study: anthropometric measures at
      different time points (birth, discharge, school-age). SUBJECTS: 136 VLBW/VP
      infants (<32weeks gestation/birth weight<1.500g). OUTCOME MEASURES: Cognitive and
      motor function (Kaufman Assessment Battery for Children; Movement Assessment
      Battery for Children) at school-age (6.7-10.0years, mean=8.2). RESULTS: In
      hierarchical multiple regression analyses, growth from birth to discharge
      significantly predicted cognitive outcome (weight: R2change=0.063, p=0.014;
      length: R2change=0.078, p=0.007; HC: R2change=0.050, p=0.030), as well as weight
      gain (R2change=0.096, p=0.001) and head growth (R2change=0.134, p<0.001) from
      discharge to school-age. While most growth parameters, especially those from
      birth to discharge, were significantly influenced by prenatal growth and
      immaturity related morbidity (R2=0.151 to 0.605, all p<=0.001), head growth after
      discharge was not (R2=0.029, p=0.461). CONCLUSIONS: Amongst all anthropometric
      measures, head growth between discharge and school-age is the best independent
      predictor for cognitive outcome in VLBW/VP infants. Determinants of head growth
      after discharge need further studies to identify targets for intervention.

PMID- 27716570
TI  - Ectopic pregnancy in simultaneous pancreas-kidney transplantation: A case report.
AB  - INTRODUCTION: We present a case report of ectopic pregnancy (EP) after
      simultaneous pancreas-kidney transplantation (SKPTx). PRESENTATION OF CASE: A 33
      year-old female status post SKPTx suddenly got abdominal pain in the lower level.
      She had high human chorionic Gonadotropin test. Ultrasonography revealed that
      there was no fetus in the uterus but a dilated right fallopian tube, which
      strongly suggested ectopic pregnancy. An emergency operation was performed and a
      dilated right side uterine tube was found with adhesions to her transplant.
      Salpingectomy was performed and no visible injury to the pancreas was found by
      the procedure. Pathological evaluation showed ectopic pregnant fetus, and no
      pancreas dysfunction was observed after the operation. DISCUSSION: This is the
      first case and operation report of EP after SKPTx. We should consider various
      causes of acute abdomen as well as several pathological condition in the
      transplanted pancreas such as pancreatitis, abscess, and thrombosis in vessels in
      the organ. Moreover, transplanted pancreas in abdomen is easily misrecognized as
      adipose tissue and there is high risk that the organ to get injured surgically.
      CONCLUSION: EP should be included in the different diagnosis in SKPTx female
      patients who get acute abdominal pain. It is highly desirable that transplant
      surgeon is included in the operation team for EP of these patients.

PMID- 27716568
TI  - Plaque structural stress assessed by virtual histology-intravascular ultrasound
      predicts dynamic changes in phenotype and composition of untreated coronary
      artery lesions.
AB  - BACKGROUND AND AIMS: We aimed to determine whether finite element analysis (FEA)
      derived plaque structural stress (PSS) analysis can predict serial changes in
      atheroma volume, type, and tissue composition within a fibroatheroma-containing
      target segment. METHODS: Overall, 210 patients (210 untreated coronary artery
      lesions) underwent serial (baseline and 12-month follow-up) grayscale- and
      virtual histology (VH)-intravascular ultrasound (IVUS). Baseline PSS was assessed
      at the minimal lumen and at the maximum necrotic core (NC) sites. RESULTS:
      Overall, there was a significant decrease in %NC volume. The highest PSS tertile
      was associated with a smaller on-statin reduction in %NC volume (-1.55 +/- 1.03%
      in the highest vs. -5.18 +/- 1.12% in the lowest tertile, p = 0.025). Of the 115
      lesions with baseline VH-thin cap fibroatheroma (TCFA), 36 (31%) showed
      persistent VH-TCFA at follow-up. Five of the 95 lesions with baseline thick-cap
      fibroatheroma evolved into VH-TCFA. Independent predictors of VH-TCFA at follow
      up (including persistent and new VH-TCFAs) were diabetes mellitus (odds ratio
      [OR] = 3.87, 95% CI = 1.58-9.47), a large MLA (OR = 1.39, 95% CI = 1.10-1.75), a
      greater percent atheroma volume (OR = 1.12, 95% CI = 1.05-1.19), VH-TCFA at
      baseline (OR = 8.01, 95% CI = 2.73-23.50), and a higher superficial PSS at the
      maximum NC site (OR = 1.02, 95% CI = 1.00-1.03), (all p < 0.05). Independent
      determinants of the serial change in %NC volume were high-sensitive C-reactive
      protein (beta = -2.79, 95% CI = -5.31 to -0.27), baseline %NC volume (beta = 
      0.70, 95% CI = -0.84 to -0.56), and superficial PSS at the maximum NC site (beta
      = 0.05, 95% CI = 0.01-0.08), (all p < 0.05). CONCLUSIONS: An elevated PSS was
      more likely associated with an increase in atheroma volume, a smaller on-statin
      reduction in %NC volumes, and the presence of VH-TCFA at follow-up. Morphologic
      and hemodynamic assessment by utilizing VH-IVUS may help understand and predict
      atherosclerotic progression.

PMID- 27716571
TI  - Pedicle screw position changing policy for nerve injury problems during screw
      insertion on thoracolumbar compression fractures.
AB  - INTRODUCTION: Intraoperative neurophysiologic monitoring (IONM) had important
      role related to the complications in spinal surgery. Somatosensory Evoked
      Potential (SSEP), Transcranial electric Muscle Evoked Potentials (tceMEPs), and
      free run EMG are parameters used to asses functional integrity of the nervous
      system during surgical procedures. Once warning signal was recognized, surgeon
      have to make a precise decision to overcome that problem. PRESENTATION OF CASE:
      We present a 47-year old male with back pain due to compression fracture of
      thoracic vertebra T12 and lumbar vertebrae L1. While stabilizing through the
      posterior approach on the T11 and 12 as well as L2 and L3, the SSEP monitor
      showed 50% reduction in the waveform as the pedicle screw was inserted at the
      left side of T12. The instrumentation was changed into vertebra thoracal T10,
      T11, and vertebrae lumbar L2, L3. The SSEP normalized and post operatively pain
      decreased. After surgery there was no neurological deficit. DISCUSSION: Acute
      trauma as a result of spine instrumentation may provoke significant edema, with
      mass effect causing neurophysiological dysfunction. Administration of intravenous
      steroid would do at this stage, followed by constant infusion for following 24
      48h, may help ameliorating the mass effect and improving the neurologic outcome.
      Alternatively, immediate pedicle screw changing policy showed absolute recovery
      of nerve injury. CONCLUSION: Insertion of pedicle screw in spinal surgery has a
      risk of complication that could be treated by pedicle screw changing policy.

PMID- 27716569
TI  - Iron citrate reduces high phosphate-induced vascular calcification by inhibiting
      apoptosis.
AB  - BACKGROUND AND AIMS: High phosphate-induced vascular calcification (VC) and iron
      deficiency-induced anemia are two major contributors of cardiovascular morbidity
      and mortality in patients affected by chronic kidney disease (CKD). Since
      phosphate (Pi) control and iron replacement are common therapies in CKD, the aim
      of our study was to investigate the effect of iron on high Pi-induced VC in rat
      vascular smooth muscle cells (VSMCs). METHODS: We treated VSMCs with 5 mM Pi and
      iron citrate (Fe3+) to evaluate Ca deposition by Alizarin Red destaining, DNA
      fragmentation by ELISA, gene expression by RT-PCR and protein expression by
      Western blot. RESULTS: Pretreatment with Fe3+ prevents high Pi-induced calcium
      (Ca) deposition concentration-dependently, with 90.1% inhibition at 50 MUM (0.716
      +/- 0.04 vs. 0.071 +/- 0.01, OD/mg protein; Pi vs. Pi + Fe3+, p < 0.01). We found
      that 50 MUM Fe3+ completely prevents high Pi-induced apoptosis measured as DNA
      fragmentation (1.51 +/- 0.08 vs. 1.03 +/- 0.06, Pi vs. Pi + Fe3+; p < 0.01),
      through the prevention of the downregulation of the pro-survival pathway
      GAS6/AXL. Moreover, Fe3+ stimulates autophagy, a protective phenomenon in VC, as
      demonstrated by electron microscopy and by autophagy flux detected by LC3IIbeta
      protein expression. Finally, high Pi-induced osteoblastic differentiation is
      partially affected by Fe3+, since BMP2 increase is prevented and OPN is enhanced,
      but RUNX2 increase and alpha-actin and SM22alpha decrease are not modified.
      Interestingly, the addition of Fe3+ at different time points after Pi challenge
      completely blocks the progression of Ca deposition. CONCLUSIONS: In conclusion,
      iron citrate inhibits high Pi-induced Ca deposition by prevention of apoptosis,
      induction of autophagy, and partially affecting osteoblastic differentiation.

PMID- 27716572
TI  - Trait and state rumination interact to prolong cortisol activation to
      psychosocial stress in females.
AB  - There is a growing realization that cognitive processes associated with stress
      coping, such as rumination and distraction, can impact the hypothalamic-pituitary
      adrenal-axis (HPA-axis). Yet, little is known about what aspects of the HPA-axis
      stress response (rate of activation, duration of activation, rate of recovery) is
      impacted by such cognitive processes. This study examines the impact of both
      ruminative trait tendencies and experimentally induced rumination on salivary
      cortisol responses to a social evaluative stress task. Participants (n=71) were
      exposed to the Trier Social Stress Test (TSST) and were then randomized to
      complete either a rumination or distraction task. Trait rumination was also
      assessed at baseline. Results showed no main effects of either trait rumination
      or experimental condition, but they interacted to predict the cortisol response.
      Specifically, participants high in trait rumination had prolonged duration of
      cortisol activation in the rumination condition, compared to those in the
      distraction condition. In contrast, cortisol responses of participants with low
      trait rumination did not differ by condition. Notably, our interaction effect was
      only significant in females. Our findings highlight the complex relationship
      between rumination and HPA-axis activity, suggesting an interaction of trait and
      state rumination in shaping HPA-axis responses to stress, and call attention to
      sex differences in this relationship.

PMID- 27716573
TI  - Oxytocin receptor gene variation rs53576 and alcohol abuse in a longitudinal
      population representative study.
AB  - BACKGROUND: Oxytocin is an important regulator of social relationships and has
      been implicated in development of substance use and addiction. We examined the
      association of a variance in the oxytocin receptor gene (OXTR rs53576
      polymorphism) with alcohol use in a population-representative sample, and
      potential moderation by social functioning. METHODS: The analysis was carried out
      on the older birth cohort of the longitudinal Estonian Children Personality
      Behaviour and Health Study (ECPBHS), a cohort of initially 15 years old children
      (original n=593) recalled at ages 18 and 25. In all data collection waves the
      participants reported the frequency of consuming alcoholic beverages. Psychiatric
      interview was carried out at age 25 to assess the lifetime prevalence of
      substance use disorders. Adverse social interactions with teachers, classmates
      and family members were self-reported at ages 15 and 18. The minor (A) allele
      frequency was 0.37. RESULTS: Males homozygous for the A allele (suggested to be
      associated with less efficient oxytocinergic functioning) were more frequent
      alcohol consumers at ages 15 and 18 and also more likely to have had alcohol
      abuse or addiction by age 25 compared to male G allele carriers. Alcohol use was
      not associated with the OXTR genotype in females. Both male and female AA
      homozygotes who had reported less favourable relations with their teachers at age
      15 more likely had alcohol use disorder. CONCLUSIONS: OXTR rs53576 polymorphism
      is associated with alcohol use and prevalence of alcohol use disorders in males,
      and this may be moderated by inferior interpersonal relationships.

PMID- 27716574
TI  - The effect of delphinidin on the mechanical properties of keratinocytes exposed
      to UVB radiation.
AB  - The usage of active compounds of dietary phytochemicals in prevention of UV
      induced skin diseases is increasingly gaining attention in the development of
      skin care products. The purpose of this study was to measure the influence of
      delphinidin (as a botanical agent) on the cell mechanical properties evaluated by
      the atomic force microscopy (AFM) technique in the immortalized human
      keratinocyte cell line (HaCaT) exposed to UVB radiation. The cells were treated
      with various doses of UVB radiation with and without pre and post-treatment with
      selected concentrations of delphinidin. The measurements of the elastic
      properties revealed that the exposure of HaCaT cells to high dose of the UVB
      radiation (100mJ/cm2) caused a decrease in the cell elastic modulus. It was
      accompanied by the decrease of metabolic activity, rearrangement of actin
      cytoskeleton and disappearance of the cell repair marker 53BP1. Both pre
      treatment and post-treatment with delphinidin at non-cytotoxic concentrations (5
      or 10MUM), restored the elastic modulus of irradiated keratinocytes. A direct AFM
      analysis showed that the UVB-mediated decrease of the cell stiffness was restored
      more effectively when cells were treated with delphinidin after the UVB
      irradiation. The results demonstrate the regenerative effect of delphinidin on
      the mechanical properties of cells exposed to UVB radiation (100mJ/cm2), which
      may be due to antioxidant and inhibitory effect on matrix metalloproteinases
      activation.

PMID- 27716575
TI  - Sustained reduction of diversion and abuse after introduction of an abuse
      deterrent formulation of extended release oxycodone.
AB  - BACKGROUND: The development of abuse deterrent formulations is one strategy for
      reducing prescription opioid misuse and abuse. A putative abuse deterrent
      formulation of oxycodone extended release (OxyContin(r)) was introduced in 2010.
      Early reports demonstrated reduced abuse and diversion, however, an analysis of
      social media found 32 feasible methods to circumvent the abuse deterrent
      mechanism. We measured trends of diversion, abuse and street price of OxyContin
      to assess the durability of the initial reduction in abuse. METHODS: Data from
      the Poison Center Program, Drug Diversion Program, Opioid Treatment Program,
      Survey of Key Informant Patients Program and StreetRx program of the Researched
      Abuse, Diversion, and Addiction-Related Surveillance (RADARS(r)) System were
      used. The average quarterly rates of abuse and diversion for OxyContin were
      compared from before reformulation to the rate in second quarter 2015. Rates were
      adjusted for population using US Census data and drug availability. RESULTS:
      OxyContin abuse and diversion declined significantly each quarter after
      reformulation and persisted for 5 years. The rate of abuse of other opioid
      analgesics increased initially and then decreased, but to lesser extent than
      OxyContin. Abuse through both oral and non-oral routes of self-administration
      declined following the reformulation. The geometric mean difference in the street
      price of reformulated OxyContin was 36% lower than the reformulated product in
      the year after reformulation. DISCUSSION: Despite methods to circumvent the abuse
      deterrent mechanism, abuse and diversion of OxyContin decreased promptly
      following the introduction of a crush- and solubility- resistant formulation and
      continued to decrease over the subsequent 5 years.

PMID- 27716577
TI  - Neurobiology and biomechanics of flight in miniature insects.
AB  - Miniature insects can be as small as a few hundred micrometres in size, making
      them among the smallest metazoan animals ever described. Yet, even at these
      length scales, they display remarkably sophisticated flight behaviours. For
      flight at such low Reynolds numbers, miniature insects have evolved biomechanical
      and neural adaptations that push the boundaries of what is possible in the realm
      of physics and neurobiology of flight. After several decades of relative
      dormancy, this question has recently been revisited by researchers working in
      diverse areas ranging from systematics and neurobiology to dispersal behaviours.
      In this review, I cover recent findings in this area, and point towards the many
      open questions that still remain unanswered.

PMID- 27716576
TI  - Correlates of nicotine dependence among adolescent waterpipe smokers.
AB  - INTRODUCTION: Waterpipe smoking is addictive and its use is increasing globally
      among youth, yet little is known about the factors associated with nicotine
      dependence (ND) among waterpipe smokers. We investigated the factors associated
      with ND symptoms among a sample of Lebanese adolescents who smoke a waterpipe.
      METHODS: We collected data on factors potentially associated with ND (individual,
      socio-demographic, environmental, smoking patterns) among 160 current (past
      30days) waterpipe smokers recruited from 8th and 9th school grades in Lebanon. We
      assessed the loss of autonomy over tobacco using the Hooked on Nicotine Checklist
      (HONC), ND using the International Classification of Diseases, 10th revision (ICD
      10), and the number of ND symptoms endorsed. RESULTS: Depressive symptoms, lower
      self-esteem, and having at least one sibling who smokes a waterpipe were
      associated with the presence of ND symptoms, while enrollment in public schools,
      smoking a waterpipe >=30min per session, and believing that cigarette smoking is
      harmful to health were associated with endorsement of a higher number of ND
      symptoms. Smoking a whole waterpipe head without sharing and being in 9th grade
      in this study were associated with the presence and endorsement of a higher
      number of ND symptoms. CONCLUSIONS: We identified specific social and
      psychological characteristics, waterpipe smoking patterns, and beliefs about
      harmful effects of smoking associated with the presence of ND among adolescent
      waterpipe smokers. Considering these factors when planning policies to prevent ND
      among waterpipe smokers is warranted.

PMID- 27716578
TI  - Maternal transfer and sublethal immune system effects of brevetoxin exposure in
      nesting loggerhead sea turtles (Caretta caretta) from western Florida.
AB  - Blooms of Karenia brevis (also called red tides) occur almost annually in the
      Gulf of Mexico. The health effects of the neurotoxins (i.e., brevetoxins)
      produced by this toxic dinoflagellate on marine turtles are poorly understood.
      Florida's Gulf Coast represents an important foraging and nesting area for a
      number of marine turtle species. Most studies investigating brevetoxin exposure
      in marine turtles thus far focus on dead and/or stranded individuals and rarely
      examine the effects in apparently "healthy" free-ranging individuals. From May
      July 2014, one year after the last red tide bloom, we collected blood from
      nesting loggerhead sea turtles (Caretta caretta) on Casey Key, Florida USA. These
      organisms show both strong nesting and foraging site fidelity. The plasma was
      analyzed for brevetoxin concentrations in addition to a number of health and
      immune-related parameters in an effort to establish sublethal effects of this
      toxin. Lastly, from July-September 2014, we collected unhatched eggs and liver
      and yolk sacs from dead-in-nest hatchlings from nests laid by the sampled females
      and tested these samples for brevetoxin concentrations to determine maternal
      transfer and effects on reproductive success. Using a competitive enzyme-linked
      immunosorbent assay (ELISA), all plasma samples from nesting females tested
      positive for brevetoxin (reported as ng brevetoxin-3[PbTx-3] equivalents [eq]/mL)
      exposure (2.1-26.7ng PbTx-3eq/mL). Additionally, 100% of livers (1.4-13.3ng PbTx
      3eq/mL) and yolk sacs (1.7-6.6ng PbTx-3eq/mL) from dead-in-nest hatchlings and
      70% of eggs (<1.0-24.4ng PbTx-3eq/mL) tested positive for brevetoxin exposure
      with the ELISA. We found that plasma brevetoxin concentrations determined by an
      ELISA in nesting females positively correlated with gamma-globulins, indicating a
      potential for immunomodulation as a result of brevetoxin exposure. While the
      sample sizes were small, we also found that plasma brevetoxin concentrations
      determined by an ELISA in nesting females significantly correlated with liver
      brevetoxin concentrations of dead-in-nest hatchlings and that brevetoxins could
      be related to a decreased reproductive success in this species. This study
      suggests that brevetoxins can still elicit negative effects on marine life long
      after a bloom has dissipated. These results improve our understanding of maternal
      transfer and sublethal effects of brevetoxin exposure in marine turtles.

PMID- 27716580
TI  - Toxicomorphomics and toxicokinetics of quinalphos on embryonic development of
      zebrafish (Danio rerio) and its binding affinity towards hatching enzyme, ZHE1.
AB  - This study outlines the toxic effects of Quinalphos (QP), an organophosphrous
      insecticide on the development of zebrafish (Danio rerio) embryos, with special
      emphasis on toxicomorphomics and toxicokinetics of target enzyme, AChE. A range
      of concentrations was used to elucidate the median lethal concentration (LC50) of
      Quinalphos. Furthermore, embryos were exposed to two sub-lethal concentrations
      LC10 (0.66mg/L) and LC20 (1.12mg/L) along with a median lethal concentration
      (3.0mg/L) for 96h. Several morphological aberrations like lordosis, kyphosis,
      scoliosis, heart edema, breaks in the neuronal tube and underdeveloped facial
      parts were noticed, which were of concentration and time dependent. The QP has
      adequately hindered hatching process during the course of exposure which was
      upheld by the in silico docking studies with hatching enzyme, ZHE1. The length of
      hatchlings at 96h in LC50 concentration was significantly reduced to 47% compared
      to control. A significant pericardial effusion (5 to 16 fold) was observed in
      >90% of LC50 treated groups. Morphological changes in heart lead to the
      bradycardia, which ultimately leading to heart failure in some cases. The
      swimming behavior was significantly diminished in relation to the inhibition of
      AChE levels. From the in vitro kinetic studies, the kinetic constants Km, Vmax
      and inhibitory concentration Ki (4.45*10-5M) was determined which supported the
      competitive nature of QP.

PMID- 27716581
TI  - A study of temporal effects of the model anti-androgen flutamide on components of
      the hypothalamic-pituitary-gonadal axis in adult fathead minnows.
AB  - The aim of this study was to investigate temporal changes in the hypothalamic
      pituitary-gonadal (HPG) axis of fathead minnows (Pimephales promelas) treated
      with the model androgen receptor (AR) antagonist flutamide. Reproductively-mature
      fish were exposed in a flow-through test to analytically-confirmed concentrations
      of either 50 or 500MUg flutamide/L for 8 d, followed by an 8-d recovery period in
      clean water. Fish were sampled at 1, 2, 4 and 8days during each phase of the
      experiment. Flutamide (500MUg/L) caused significant reductions in relative gonad
      size of the females on day 8 of the exposure and day 1 of the recovery, and
      reduced expression of secondary sex characteristics in males during the exposure
      phase of the experiment. Ex vivo gonadal synthesis of testosterone in both sexes
      (and 17beta-estradiol in females) was reduced in the 500MUg/L treatment within 2
      d of exposure; however, steroid synthesis returned to levels comparable to
      controls by the end of the exposure portion of the test. Ex vivo testosterone
      synthesis in males exposed to 50MUg flutamide/L was greater than in controls on
      days 4 and 8 of the exposure. Both the enhanced steroid production in the low
      treatment males, and return to control levels in the high treatment males and
      females during chemical exposure are indicative of a compensatory HPG response.
      One contributor to this response could be increased expression of genes
      responsible for enzymes involved in steroid synthesis; for example, transcripts
      for both cytochrome P450 side- chain cleavage and 11beta-hydroxysteroid
      dehydrogenase were significantly elevated in flutamide-exposed males. Overall,
      responses of the HPG axis in adult male and female fathead minnows exposed to
      flutamide were both dynamic and comparatively rapid during exposure and recovery.
      These observations have ramifications both for the development of short-term fish
      assays to detect endocrine-active chemicals, and the derivation of robust adverse
      outcome pathways for AR antagonists in fish.

PMID- 27716582
TI  - Measurement of large nonlinear refractive index of natural pigment extracted from
      Hibiscus rosa-sinensis leaves with a low power CW laser and by spatial self-phase
      modulation technique.
AB  - We have reported here, for the first time, to the best of our knowledge, a high
      nonlinear refractive index (n2e) of a natural pigment extracted from Hibiscus
      rosa-sinensis leaves by using spatial self-phase modulation technique (SSPM) with
      a low power CW He-Ne laser radiation at 632.8nm. It is found by UV-Vis absorption
      spectroscopic analysis that chlrophyll-a, chlrophyll-b and carotenoid are present
      in the pigment extract with 56%, 25% and 19%, respectively. The photoluminescence
      (PL) emission characteristics of the extracted samples have also been measured at
      room temperature as well as in the temperature range of 283-333K to investigate
      the effect of temperature on luminescent properties of the sample. By analyzing
      the SSPM experimental data, the nonlinear refractive index value of pigment
      extract has been determined to be 3.5*10-5cm2/W. The large nonlinear refractive
      index has been assigned due to asymmetrical structure, molecular reorientation
      and thermally induced nonlinearity in the sample. The presented results might
      open new avenues for the green and economical technique of syntheses of organic
      dyes with such a large nonlinear optical property.

PMID- 27716583
TI  - The thermochromic behavior of aromatic amine-SO2 charge transfer complexes.
AB  - The distinct thermochromism observed in solutions containing N,N-dimethylaniline
      (DMA) and N,N-diethylaniline (DEA) and SO2 was investigated by resonance Raman
      spectroscopy in a wide range of temperatures. The results indicate in addition to
      the charge transfer (CT) complexes DMA-SO2 and DEA-SO2, the presence of collision
      complexes involving the CT complexes and excess DMA and DEA molecules. The latter
      in fact is the chromophore responsible for the long wavelength absorption
      originating the color. The Raman signature of the collision complex was
      attributed to the distinct enhancement of a band at 1140cm-1 assigned to
      nus(SO2), in contrast to the same mode in the 1:1 complex at 1115cm-1. The
      intensity of such band, assigned to the collision complex is favored at high
      temperatures and depends on the steric hindrance associated to amines, as well as
      the SO2 molar fraction. Quantum chemical calculations based on time-dependent
      density functional theory (TDDFT) support the proposed interpretation.

PMID- 27716579
TI  - The transcription factor, Nuclear factor, erythroid 2 (Nfe2), is a regulator of
      the oxidative stress response during Danio rerio development.
AB  - Development is a complex and well-defined process characterized by rapid cell
      proliferation and apoptosis. At this stage in life, a developmentally young
      organism is more sensitive to toxicants as compared to an adult. In response to
      pro-oxidant exposure, members of the Cap'n'Collar (CNC) basic leucine zipper (b
      ZIP) transcription factor family (including Nfe2 and Nfe2-related factors, Nrfs)
      activate the expression of genes whose protein products contribute to reduced
      toxicity. Here, we studied the role of the CNC protein, Nfe2, in the
      developmental response to pro-oxidant exposure in the zebrafish (Danio rerio).
      Following acute waterborne exposures to diquat or tert-buytlhydroperoxide (tBOOH)
      at one of three developmental stages, wildtype (WT) and nfe2 knockout (KO)
      embryos and larvae were morphologically scored and their transcriptomes
      sequenced. Early in development, KO animals suffered from hypochromia that was
      made more severe through exposure to pro-oxidants; this phenotype in the KO may
      be linked to decreased expression of alas2, a gene involved in heme synthesis. WT
      and KO eleutheroembryos and larvae were phenotypically equally affected by
      exposure to pro-oxidants, where tBOOH caused more pronounced phenotypes as
      compared to diquat. Comparing diquat and tBOOH exposed embryos relative to the WT
      untreated control, a greater number of genes were up-regulated in the tBOOH
      condition as compared to diquat (tBOOH: 304 vs diquat: 148), including those
      commonly found to be differentially regulated in the vertebrate oxidative stress
      response (OSR) (e.g. hsp70.2, txn1, and gsr). When comparing WT and KO across all
      treatments and times, there were 1170 genes that were differentially expressed,
      of which 33 are known targets of the Nrf proteins Nrf1 and Nrf2. More
      specifically, in animals exposed to pro-oxidants a total of 968 genes were
      differentially expressed between WT and KO across developmental time,
      representing pathways involved in coagulation, embryonic organ development, body
      fluid level regulation, erythrocyte differentiation, and oxidation-reduction,
      amongst others. The greatest number of genes that changed in expression between
      WT and KO occurred in animals exposed to diquat at 2h post fertilization (hpf).
      Across time and treatment, there were six genes (dhx40, cfap70, dnajb9b, slc35f4,
      spi-c, and gpr19) that were significantly up-regulated in KO compared to WT and
      four genes (fhad1, cyp4v7, nlrp12, and slc16a6a) that were significantly down
      regulated. None of these genes have been previously identified as targets of Nfe2
      or the Nrf family. These results demonstrate that the zebrafish Nfe2 may be a
      regulator of both primitive erythropoiesis and the OSR during development.

PMID- 27716584
TI  - Toxicity evaluation of selected ammonium-based ionic liquid forms with MCPP and
      dicamba moieties on Pseudomonas putida.
AB  - Combination of the hydrophilic herbicidal anion with hydrophobic, antimicrobial
      ammonium cation allows to obtain compounds in ionic liquid form with better
      properties then conventional herbicides. Both cation and anion can be modified by
      selection of herbicide and the length of alkyl chains in cation structure.
      However the knowledge of their potential toxic effects are still limited.
      Furthermore, the relation between hydrophobicity associated with the length of
      alkyl chains and toxicity for ionic liquids has not been thoroughly studied.
      Therefore we investigated toxic effects of herbicidal ionic liquid forms on
      growth inhibition, given as EC50, of the common soil bacterium Pseudomonas
      putida. We thereby concentrated on quaternary ammonium salts. Analyzed compounds
      were composed of dicamba or MCPP moieties and cation with various alkyl chain
      lengths (n = 6,8,10) We compared them with commercial herbicides, and ammonium
      based ionic liquids with neutral anion (Br-). In addition, cis-trans
      isomerisation of unsaturated membrane fatty acids in Pseudomonas putida was
      applied as the proxy for toxicity and membrane activity. We showed that toxicity
      increased with the length of alkyl chains. However, this correlation is only
      valid for six and eight carbon atom in alkyl chains, where for n = 10 the EC50
      values rise by one order of magnitude. In our studies, the herbicidal ionic
      liquids [C10,C10,C1,C1N][MCPP] and [C10,C10,C1,C1N][dicamba] showed the lowest
      toxicity among analyzed quaternary ammonium salts and comparable toxicity with
      corresponding herbicides. No clear increase in toxicity could be followed by
      changing the anion moieties for ammonium-based ionic liquid forms.

PMID- 27716585
TI  - A review: Potential and challenges of biologically activated carbon to remove
      natural organic matter in drinking water purification process.
AB  - The use of biologically activated carbon (BAC) in drinking water purification is
      reviewed. In the past BAC is seen mostly as a polishing treatment. However, BAC
      has the potential to provide solution to recent challenges faced by water
      utilities arising from change in natural organic matter (NOM) composition in
      drinking water sources - increased NOM concentration with a larger fraction of
      hydrophilic compounds and ever increasing trace level organic pollutants.
      Hydrophilic NOM is not removed by traditional coagulation process and causes
      bacterial regrowth and increases disinfection by-products (DBPs) formation during
      disinfection. BAC can offer many advantages by removing hydrophilic fraction and
      many toxic and endocrine compounds which are not otherwise removed. BAC can also
      aid the other downstream processes if used as a pre-treatment. Major drawback of
      BAC was longer empty bed contact time (EBCT) required for an effective NOM
      removal. This critical review analyses the strategies that have been adopted to
      enhance the biological activity of the carbon by operational means and summarises
      the surface modification methods. To maximize the benefit of the BAC, a rethink
      of current treatment plant configuration is proposed. If the process can be
      expedited and adopted appropriately, BAC can solve many of the current problems.

PMID- 27716586
TI  - Removal of anionic pollutants by pine bark is influenced by the mechanism of
      retention.
AB  - The use of organic biosorbents for anion removal from water has been less studied
      than for cationic compounds. In this work, the removal capacity of pine bark for
      potential anionic pollutants (fluoride, phosphate, arsenate and dichromate) was
      assessed in column experiments, designed to study the process of transport. The
      results showed that pine bark has a very low retention capacity for phosphate,
      arsenate or fluoride, and in turn, very high for dichromate, with retention
      values close to 100% and less than 2% desorption of the adsorbed dichromate. The
      large differences observed between anions suggest that differences in the
      retention mechanism of each anion exist. In the case of phosphate and arsenate,
      electrostatic interactions with the mostly negatively charged functional groups
      of the pine bark determine the low retention capacity. Dichromate retention might
      proceed through reduction of chromium (VI) to chromium (III), what improves the
      efficiency of the removal.

PMID- 27716587
TI  - Removal of boron from wastewater: Evaluation of seven poplar clones for B
      accumulation and tolerance.
AB  - Boron (B) contamination of wastewater is a serious environmental and health
      problem, which has proved difficult to remediate. One potential approach is
      phytoremediation, i.e., the use of plants to extract B into the shoot systems,
      which can then be harvested and removed. The purpose of this study was to
      investigate the ability of seven hybrid poplar clones to accumulate and tolerate
      B at different levels of B and salinity. The clones were grown in quarter
      strength Hoagland's nutrient solution and exposed to four B treatments: 0.25, 25,
      75 and 125 mg B L-1 in factorial combination with three salinity treatments: 0,
      0.5 and 5 g L-1. Measurements were made of biomass (dry weight) and B
      concentrations (analyzed by inductively coupled plasma-optical emission
      spectroscopy) of plant tissues. The results showed that, with increasing level of
      B supply, the B concentrations in the shoot tissue of the poplar clones
      increased, while shoot biomass decreased. Comparison of the seven different
      poplar clones revealed that the clone designated 195-529 exhibited the greatest
      ability for B accumulation and tolerance. Generally, the 0.5 g L-1 level of
      salinity was beneficial for poplar growth and B removal, while the high salinity
      level of 5 g L-1 significantly inhibited poplar growth and B translocation from
      roots to shoots. Based on the results obtained with this hydroponic system, the
      clone 195-529 (P. trichocarpa * P. deltoides) is likely to be the most useful for
      the removal of B from B contaminated wastewater.

PMID- 27716588
TI  - A new integrated strategy for direct current cardioversion in non-valvular atrial
      fibrillation patients using short term rivaroxaban administration: The
      MonaldiVert real life experience.

PMID- 27716589
TI  - Changes of proteoglycan and collagen II of the adjacent intervertebral disc in
      the cervical instability models.
AB  - OBJECTIVE: Post-operation of cervical decompression fusion and internal fixation
      (CDF) accelerated adjacent segment disc degeneration (ASD). It is not clear that
      whether instability of one single segmental accelerates the degeneration of
      adjacent segment disc. This study aims to explore the effect of cervical
      instability on the change of morphology and biochemistry in adjective segment
      (above) in the L5/6 cervical instability rabbit models. METHODS: Thirty-two
      mature New Zealand white rabbits (3000+/-250g) were randomly divided into two
      groups, control group (n=8) and model group (n=24). The animal models were
      established by destruction of partly annulus fibrosus and suction of nucleus
      pulposus. ASD was detected by X-ray after 4, 8 or 12 weeks surgery (8 model
      rabbits of each time). Animals were then euthanatized for cervical intervertebral
      disc tissue samples separation. Histomorphology, proteoglycan and collagen II of
      samples were detected. RESULTS: Histomorphology data showed that notochord cells
      were decreased in C4/5 cervical nucleus pulposus and were replaced by fibroblast
      like cells; a small amount cartilage cells were emerged; intervertebral disc
      anulus fibrosus becomes rough, disorganized, hyaline degeneration and
      pigmentation, in which contained fibrocartilage cells and cracks between the
      inner and outer layers. Proteoglycan content of nucleus pulposus was
      significantly decreased. Meanwhile, type II collagen of nucleus pulposus and
      annulus was also apparently reduced. CONCLUSION: Cervical instability can alter
      morphology and reduce the content of proteoglycan and collagen II in adjacent
      intervertebral disc, thereby contributes adjacent intervertebral disc
      degeneration.

PMID- 27716590
TI  - Therapeutic effects of Aloe spp. in traditional and modern medicine: A review.
AB  - Traditional medicine is a useful guide in medical sciences. In the Islamic
      Iranian traditional medicine, the medicinal properties of many plants have been
      mentioned that could be exploited in drug discovery. We aimed to explore the
      nature and properties of Aloe spp. As described in some major Islamic traditional
      texts including Ferdows al-Hekmah fi'l-Tibbe (The Paradise of Wisdom in
      Medicine), Al-Hawi fi'l-Tibb (Comprehensive Book of Medicine), Kamel al-Sanaat al
      Tibbyyah (Complete Book of the Medical Art), Al-Qanun fi'l-Tibb (Canon of
      Medicine), Zakhireh Kharazmshahi (Treasure of Kharazmshah), and Makhzan al-Adwiah
      (Drug Treasure), and assess the conformity of traditional medicine instructions
      with the findings of modern pharmacological studies. Gastrointestinal activities,
      hepato-protective properties, beneficial effects against skin problems such as
      wounds, injuries, and infective diseases are among the most frequently mentioned
      properties of Aloe spp. Several activities of Aloe spp. described in traditional
      medicine have been the subject of recent in vitro and in vivo studies as well as
      clinical trials. Owing to the positive findings, different preparations of Aloe
      spp. are now present in pharmaceutical markets such as Aloe cosmetic products. On
      the other hand, there are many traditional therapeutic effects of Aloe spp. which
      have not been studied and require confirmatory experimental or clinical
      investigations. It is hoped that the present study could stimulate further
      research on the unexplored aspects of the medicinal properties of Aloe spp.

PMID- 27716591
TI  - TACE combined with dendritic cells and cytokine-induced killer cells in the
      treatment of hepatocellular carcinoma: A meta-analysis.
AB  - Patients with hepatocellular carcinoma (HCC), a fatal cancer, have benefited
      significantly from TACE (transcatheter arterial chemoembolization) and
      immunotherapy treatments. Immunotherapy that includes dendritic cells and
      cytokine-induced killer cells (DC-CIK) in combination with TACE has been
      extensively applied in cases of HCC. Few decisive conclusions about these
      combined effects on the outcomes of HCC patients have been reached. Therefore,
      the present meta-analysis was performed to compare the efficacy of the combined
      usage of DC-CIK with TACE with a TACE therapy alone on the outcomes of HCC
      patients. Participants were enrolled in eight eligible trials. The efficiency and
      safety of TACE followed by DC-CIK immunotherapy (experimental group) and of TACE
      alone (control group) were compared. The meta-analysis results demonstrated that
      TACE plus DC-CIK immunotherapy is possibly superior to TACE alone in promoting a
      better overall response, for half-year, 1-year, and 2-year overall survival (OS),
      median overall survival (OS) and progression-free survival rates (PFS) in HCC
      patients. Further studies should be performed to confirm the effect of the
      combined therapy.

PMID- 27716592
TI  - Discovery and preclinical development of a novel prodrug conjugate of mesalamine
      with eicosapentaenoic acid and caprylic acid for the treatment of inflammatory
      bowel diseases.
AB  - Mesalamine (5-ASA) is one of the drugs indicated as first line therapy in
      ulcerative colitis for induction and maintenance of remission. Sulfasalazine and
      formulations of 5-ASA (pH-dependent and controlled release formulations) were
      developed to minimize the systemic absorption and maximize the delivery of the
      mesalamine to colon. Although, its efficacy and safety is well documented there
      are approximately 30% nonresponders to 5-ASA therapy. This necessitates the need
      for novel therapeutic options to improve the efficacy and safety of the currently
      available 5-ASA therapy. CLX-103 is a novel, patented prodrug molecular conjugate
      of mesalamine, eicosapentaenoic acid and caprylic acid designed to offer
      incremental benefits over the currently approved 5-ASA formulations. Results of
      in vitro and in vivo studies showed that CLX-103, was stable in simulated gastric
      fluid, but undergoes enzymatic hydrolysis in the small/large intestines to
      release the active moiety. Our data also showed that the active moiety is
      retained in the targeted intestinal tissues (ileum and colon) over a longer
      period of time in relation to sulfasalazine. The in vitro data supports the
      observed in vivo plasma kinetics of 5-ASA characterized by longer Tmax, low Cmax
      after the oral administration of CLX-103. Efficacy study of CLX-103 in acute
      dextran sodium sulfate (DSS) mouse colitis model showed improved potency measured
      as Disease Activity Index (DAI) and histological scores in the colon as compared
      to sulfasalazine. These findings indicate that CLX-103 could offer a
      differentiated drug product which is more efficacious and safer than the
      currently approved 5-ASA formulations in the treatment of inflammatory bowel
      diseases.

PMID- 27716593
TI  - Effects of macrophyte development on the oxygen metabolism of an urban river
      rehabilitation structure.
AB  - To compensate for fairway enlargements and the hydraulic impacts of navigation
      activity, an artificial rehabilitation structure was constructed in the urban,
      navigable River Spree in 2004. This wave-protected, shallow littoral zone proved
      to be highly effective in reducing vessel-induced waves and provided suitable
      conditions for the development of aquatic plants. However, in time it became less
      suitable for other aquatic organisms due to hypoxic conditions in late summer.
      This study aimed to comparatively calculate and analyze the oxygen balance of the
      rehabilitation structure and the main channel five years after the construction
      in 2009. In the rehabilitation structure, the production to respiration ratio
      ranged between 0.10 and 0.34 at the peak of vegetation density, while in the main
      channel in front of the rehabilitation structure it ranged between 0.67 and 0.86.
      Dense vegetation limited the water exchange and caused oxygen depletion. Thus,
      atmospheric oxygen input through the water surface and due to long-term water
      level changes became the most important supply processes for oxygen in the
      rehabilitation structure. Enhancing the oxygen supply to improve the suitability
      of the rehabilitation structure for other aquatic taxa requires an increase in
      water exchange with the main channel, e.g. by adaptively increasing the lateral
      connectivity.

PMID- 27716594
TI  - A label-free fluorescent direct detection of live Salmonella typhimurium using
      cascade triple trigger sequences-regenerated strand displacement amplification
      and hairpin template-generated-scaffolded silver nanoclusters.
AB  - The harm of Salmonella typhimurium (S. typhimurium) to public health mainly by
      the consumption of contaminated agricultural products or water stresses an urgent
      need for rapid detection methods to help control the spread of S. typhimurium. In
      this work, an intelligently designed sensor system took creative advantage of
      triple trigger sequences-regenerated strand displacement amplification and self
      protective hairpin template-generated-scaffolded silver nanoclusters (AgNCs) for
      the first time. In the presence of live S. typhimurium, single-stranded trigger
      sequences were released from aptamer-trigger sequences complex, initiating a
      branch migration to open the hairpin template I containing complementary
      scaffolds of AgNCs. Then the first strand displacement amplification was induced
      to produce numerous scaffolds of AgNCs and reporter strands which initiated a
      branch migration to open the hairpin template II containing complementary
      scaffolds of AgNCs. Then the second strand displacement amplification was induced
      to generate numerous scaffolds of AgNCs and trigger sequences which initiated the
      third branch migration and strand displacement amplification to produce numerous
      scaffolds of AgNCs and reporter strands in succession. Cyclically, the
      reproduction of the trigger sequences and cascade successive production of
      scaffolds were achieved successfully, forming highly fluorescent AgNCs, thus
      providing significantly enhanced fluorescent signals to achieve ultrasensitive
      detection of live S. typhimurium down to 50 CFU/mL with a linear range from 102
      to 107CFU/mL. It is the first report on a fluorescent biosensor for detecting
      viable S. typhimurium directly, which can distinguish from heat denatured S.
      typhimurium. And it develops a new strategy to generate the DNA-scaffolds for
      forming AgNCs.

PMID- 27716595
TI  - Madness in the movies: An evaluation of the use of cinema to explore mental
      health issues in nurse education.
AB  - The research literature on the use of cinema in nurse education is relatively
      small. This study evaluates student nurses' learning experiences of a new
      undergraduate elective module called Madness in the Movies. Ethical approval was
      granted to conduct the study. Data were collected through an online survey and a
      social media discussion forum. The anonymous online survey responses were
      collated via Survey Monkey. Content analysis was conducted on the data from the
      Facebook discussion threads to understand, interpret and conceptualise the
      meanings from the data. All study participants agreed that their understanding of
      mental health issues was enriched, their attitudes and beliefs enhanced and their
      confidence to talk about mental health concerns increased significantly. This
      module provides a fruitful approach to encourage critical reflection on mental
      health issues in a safe environment that closely mirrors authentic practice
      experiences. The module facilitates the development of students' knowledge,
      values and attitudes in relation to person-centred mental healthcare.

PMID- 27716596
TI  - Assessment of Mastoid Function with Magnetic Resonance Imaging after Canal Wall
      Up Cholesteatoma Surgery.
AB  - OBJECTIVE: To use magnetic resonance imaging (MRI) to assess the extent of
      mastoid opacification after canal wall up (CWU) cholesteatoma surgery. MATERIALS
      AND METHODS: Thirty-five children in whom post-operative MRI had been obtained
      after CWU surgery. Cholesteatoma confined to the meso- and/or epi-tympanum was
      removed using a transcanal approach (n=18). More extensive disease required a
      combined approach tympanomastoidectomy (CAT, n=17). Mastoid opacification was
      assessed in both ears by a neuroradiologist blind to surgical details using an
      ordinal scale from 0 (no opacification) to 6 (completely opacified). The primary
      outcome measure was presence of normal mastoid ventilation, defined by evaluation
      of non-operative ears as a score <=2. The presence of normal ventilation, as well
      as the raw opacification scores, were compared according to type of cholesteatoma
      surgery: 1) transcanal, with no mastoidectomy and 2) CAT. RESULTS: Mastoid
      ventilation was normal in 18 post-operative ears (51%). There was no significant
      difference in the proportion of normally ventilated mastoids in the CAT (n=17)
      and transcanal (n=18) groups (p=0.318; Fisher's exact). However, mastoid
      opacification scores were significantly higher in the CAT group than in the
      transcanal group (p=0.036; Mann-Whitney U). CONCLUSION: The mastoid frequently
      fails to become normally ventilated after cholesteatoma surgery. Subgroup
      analysis suggests cortical mastoidectomy does not increase the likelihood of
      normal mastoid ventilation after CWU cholesteatoma surgery. MRI provides a non
      invasive tool to assess mastoid function, which contributes to the current debate
      on optimum surgical strategies for management of the mastoid in cholesteatoma
      surgery. Further research will determine whether this measure of mastoid health
      correlates with risk of recurrent cholesteatoma.

PMID- 27716597
TI  - Comparison of Hyaluronic Acid Fat Graft Myringoplasty, Fat Graft Myringoplasty
      and Temporal Fascia Techniques for the Closure of Different Sizes and Sites of
      Tympanic Membrane Perforations.
AB  - OBJECTIVE: To compare the efficacy of three different myringoplasty techniques,
      namely hyaluronic acid fat graft myringoplasty (HAFGM), fat graft myringoplasty
      (FGM), and temporal fascia for the closure of different sizes and sites of
      tympanic membrane perforations. MATERIALS AND METHODS: We retrospectively
      analyzed the medical records of patients who had undergone a type 1 tympanoplasty
      operation at our clinic between May 2007 and February 2013. The patients were
      divided into three groups depending on the patient's choice of technique as
      follows: Fat Graft Myringoplasty (FGM) (Group I), Hyaluronic Acid Fat Graft
      Myringoplasty (HAFGM) (Group II), and Temporalis Fascia (TF) (Group III). A total
      of 136 patients were included in the study, split in to the FGM (57 patients;
      56.1% female; median age: 30 years), HAFGM (31 patients; 54.8 female; median age:
      25 years), and TF (48 patients; 58.3% females; median age: 33 years) surgery
      technique groups. RESULTS: The patients were further divided into two groups,
      depending on the size of the perforation (small and large), and into three
      groups, depending on its location (anterior, inferior, and central). None of
      techniques provided a significantly better success rate in terms of perforation
      location (p>0.05). Also, none of the techniques provided a significantly better
      success rate in terms of perforation size (p>0.05). CONCLUSION: We propose using
      HAFGM for large perforations and FGM alone for small perforations. The TF
      technique is a successful and well-defined technique for tympanic membrane
      perforations; however, in our opinion, its technical difficulties make it a
      secondary choice, particularly for small-sized perforations.

PMID- 27716598
TI  - Clinical Analysis of Paper Patch Myringoplasty in Patients with Tympanic Membrane
      Perforations.
AB  - OBJECTIVE: The aims of our study were to evaluate the outcome of office-based
      paper patch grafting in tympanic membrane (TM) perforation regardless of the
      disease duration or etiology and to compare the clinical factors influencing the
      successful closure of perforation between the success and failure groups of paper
      patch myringoplasty. MATERIALS AND METHODS: This is a retrospective study of 114
      patients that underwent paper patch myringoplasty in an outpatient setting
      (success group, 83 cases; failure group, 31 cases). Thirteen clinical factors
      with potential impact on the healing status of the TM were investigated: gender,
      age, laterality, etiology, duration of perforation, tinnitus, hearing loss,
      otorrhea, size and location of perforation, status of contralateral ear,
      ipsilateral findings of computed tomography, and duration of complete healing.
      The follow-up period was at least 1 year. RESULTS: The total success rate of
      paper patch grafting was 72.8%. The mean age of the failure group was
      significantly more higher than that of the success group. Significant differences
      in the etiology as well as in the history of otorrhea were found between the
      success and failure groups. There were no significant differences for any of the
      other factors between chronic and non-chronic perforations. CONCLUSION: The
      predictors of successful outcome were patient's age, etiology of perforation, and
      history of otorrhea. Clinicians can attempt paper patch myringoplasty first in
      younger patients, traumatic TM perforation cases, and in patients with no history
      of otorrhea. Paper patch grafting can also be considered before formal surgical
      myringoplasty in the case of small, dry, chronic TM perforations.

PMID- 27716599
TI  - Lateral Attic Wall Reconstruction with Glass Ionomer Bone Cement in the
      Management of Primary Acquired Attic Cholesteatoma in Children: A Preliminary
      Experience.
AB  - OBJECTIVE: To assess the effectiveness of glass ionomer bone cement (GIBC) in
      lateral attic wall reconstruction after primary acquired attic cholesteatoma
      surgery. MATERIALS AND METHODS: This prospective study was conducted on twenty
      children collected from the ENT outpatient clinics of a secondary and tertiary
      hospital. All patients presented with chronic suppurative otitis media with
      cholesteatoma of the primary acquired attic type. All patients underwent intact
      canal wall mastoidectomy (ICWM) with a transcanal atticotomy to address primary
      cholesteatoma involving the attic and the supratubal recess. Removal of the incus
      with or without decapitation of the malleus depended on the extension of the
      pathology. GIBC was used to build up the lateral attic wall in all cases.
      Ossiculoplasty and tympanoplasty were performed according to the extent of
      disease. RESULTS: All patients had integrated skin covering the reconstructed
      attic wall with no signs of granulation tissue formation, canal wall edema, glass
      ionomer extrusion, or foreign body reaction on the 6th month, 1st year and 2nd
      year follow-up visits. Also, no persistent otorrhea was noted. The postoperative
      air-bone gap was significantly improved (p=0.007). CONCLUSION: GIBC could be
      considered as a reliable artificial material for reconstruction of the lateral
      attic wall after transmeatal atticotomy in ICWM, making it feasible to avoid
      cavity problems of canal wall down mastoidectomy, especially in children.

PMID- 27716600
TI  - Comparison of Videonystagmography and Audiological Findings after Stapedotomy;
      CO2 Laser vs Perforator.
AB  - OBJECTIVE: Various types of laser, microdrill, and perforator are effectively
      used in the surgical treatment of otosclerosis. However, they have certain
      disadvantages along with advantages. The aim of this study was to evaluate the
      effects of carbon dioxide (CO2) laser and perforator stapedotomy techniques on
      audiological outcomes and postoperative vestibular functions via
      videonystagmography (VNG). MATERIALS AND METHODS: This prospective and randomized
      clinical study was conducted in an academic tertiary medical center. Sixty-nine
      patients diagnosed with otosclerosis who underwent stapedotomy were enrolled in
      this study. Patients were divided into two groups based on the technique used in
      stapedotomy: CO2 laser and perforator. Postoperative hearing gain and VNG
      findings were the main outcome measures. Subsequently, the two study groups were
      compared for analysis. RESULTS: The preoperative air-bone gap was 32.7+/-8.9
      decibel (dB) in the study population and it was improved to 12.9+/-8.4 dB after
      operation. There were no differences in VNG findings and vertigo symptoms between
      the laser and perforator groups at postoperative day 2. There was no significant
      gain difference regarding the air conduction, bone conduction, and air-bone gap
      between the two groups (p=0.294, p=0.57, and p=0.37, respectively). CONCLUSION:
      Both CO2 laser and perforator stapedotomy have successful audiological outcomes
      with no difference in postoperative vestibular disturbance.

PMID- 27716601
TI  - Diameter of the Medial Side of the Cochlear Aqueduct Is Narrower in Meniere's
      Disease: A Radiologic Analysis.
AB  - OBJECTIVE: This study aimed to measure the radiological dimensions of the
      cochlear aqueduct in Meniere's disease and in low-frequency hearing loss (LFHL)
      patients and control patients. MATERIALS AND METHODS: Groups of 26 patients (32
      ears, including 6 with bilateral involvement) with Meniere's disease, 14 patients
      (18 ears) with LFHL, and 23 patients with unilateral chronic otitis media, as
      controls, were enrolled. For the measurements, high-resolution computed
      tomography (HRCT) of the temporal bone was performed. The cochlear aqueduct was
      evaluated for the following six parameters: medial opening (MO), petrous apex
      (PA), otic capsule (OC), lateral opening (LO), distance of the cochlear aqueduct
      (DC), and length of the cochlear aqueduct (LC). RESULTS: The PA, OC, DC, and LC
      were not significantly different between the groups. LO could not be measured
      because the LO was not visible in all cases. The MO diameter was narrower in the
      Meniere's disease group than in the LFHL group (p=0.001) and in the controls
      (p=0.035). When the dimensions of both ears were measured in patients with
      unilateral Meniere's disease, no statistically significant difference was found.
      CONCLUSION: Compared to LFHL and controls, the MO of the cochlear aqueduct was
      significantly smaller in the Meniere's disease group.

PMID- 27716602
TI  - Evaluation of the Vestibular System and Etiology in Children with Unilateral
      Sensorineural Hearing Loss.
AB  - OBJECTIVE: The aim of this study was to evaluate the vestibular system of
      children with unilateral sensorineural hearing loss (USNHL), investigate the
      etiological factors of USNHL and analyze whether a genetic predisposition exists.
      MATERIALS AND METHODS: Thirty-three children aged less than 18 years with USNHL,
      who visited the ear, nose, and throat (ENT) department between January 2004 and
      December 2012, were included in this study. Cases with conductive hearing loss
      were excluded from the study. The patients were subjected to etiologic, genetic,
      and ophthalmologic evaluation; radiologic imaging; electronystagmography (ENG);
      and vestibular evoked myogenic potential (VEMP) tests. The control group, which
      included 25 healthy children (13 males and 12 females), had undergone
      audiological assessment and were subjected to ENG and VEMP tests. RESULTS: All of
      the patients had severe-to-profound hearing loss. Mumps immunoglobulin G was
      positive in 22 (66.7%) of 33 patients. The 35delG mutation was not found in any
      of the patients. All of the patients underwent temporal computed tomography (CT)
      and magnetic resonance imaging (MRI). Inner ear anomaly was present in 51.5% of
      the patients. Overall, 21 of 31 ENG patients had canal paresis in the affected
      ear. The VEMP response was absent on the affected side in three patients. The n23
      latency average of the patient group was longer than that of the control group.
      CONCLUSION: Because USNHL causes irreversible problems in children, early
      diagnosis and auditory rehabilitation are very important. As USNHL is accompanied
      by inner ear anomaly, children with USNHL should undergo temporal bone CT and
      MRI. To evaluate the vestibular system, ENG and VEMP are non-invasive and
      diagnostic tests.

PMID- 27716603
TI  - Do Vestibular-Evoked Myogenic Potential Abnormalities in Patients with Cochlear
      Implant Only Reflect Saccular Dysfunction?
AB  - OBJECTIVE: The objective of this study was to explore the usefulness of 1000-Hz
      tone burst (TB) stimuli for detecting cervical vestibular-evoked myogenic
      potential (cVEMP) abnormalities in patients with a cochlear implant (CI).
      MATERIALS AND METHODS: Thirty asymptomatic patients who received unilateral CI
      because of severe bilateral sensorineural hearing loss were assessed for cVEMP
      produced by TB stimuli at two frequencies (500 and 1000 Hz) in the airway. VEMPs
      were recorded when the devices were switched to the on (CI-on) and off (CI-off)
      positions. RESULTS: At the CI-on position, the surgical side (SS) 500-Hz response
      rates (15/30) were significantly higher than the SS 1000-Hz response rates (9/30)
      (p=0.031), while the non-operated control side (CS) 500-Hz response rates (20/30)
      were higher than the CS 1000-Hz response rates (18/30), but the difference was
      not significant (p=0.50). At the CI-on position, the SS 500-Hz response rates
      (15/30) were lower than the CS 500-Hz response rates (20/30), but the difference
      was not significant (p=0.063). However, the SS 1000-Hz response rates (9/30) were
      significantly lower than the CS 1000-Hz response rates (18/30) (p=0.004). When
      there was no significant difference between the 500-Hz amplitudes on either side,
      the SS 1000-Hz amplitudes were found to be significantly lower (p=0.04).
      CONCLUSION: CIs have the potential to cause mechanical damage and electrical
      stimulation to the vestibular system. Possible implant-mediated mechanical damage
      and electrical stimulation in the high-frequency region affecting the cVEMP
      response could be found by a 1000-Hz stimulus.

PMID- 27716604
TI  - Effect of a 4-Week Treatment with Cilostazol in Patients with Chronic Tinnitus: A
      Randomized, Prospective, Placebo-controlled, Double-blind, Pilot Study.
AB  - OBJECTIVE: The aim of this prospective, double-blind, randomized, placebo
      controlled study was to evaluate the efficacy of cilostazol, a selective
      phosphodiesterase 3 inhibitor, in patients with chronic tinnitus. MATERIALS AND
      METHODS: Adult patients of chronic tinnitus lasting more than 3 months were
      included. Fifty eligible patients were randomly assigned to either cilostazol or
      control (placebo) group. The study medication of oral 100-mg cilostazol and a
      matching placebo were used twice a day for 4 weeks. Subjective tinnitus severity
      was evaluated using the visual analog scale (VAS), tinnitus handicap inventory
      (THI), and Short-Form 36 health survey (SF-36) at baseline and at 2 and 4 weeks
      after study initiation. Changes in tinnitus pitch and loudness matching values
      were also analyzed. RESULTS: The improvement range in the VAS score was
      significantly greater in the cilostazol group than in the placebo group after 4
      weeks' administration of cilostazol. The SF-36 subscales also showed improvement
      in quality of life in the physical component summary subscale, the aggregate
      subscale of the physical category. There were no significant improvements in the
      cilostazol group compared to the placebo group in the THI subscales and tinnitus
      characteristics of pitch and loudness matching values. Various degrees of
      headaches were experienced by 68% of patients in the cilostazol group.
      CONCLUSION: A 4-week administration of oral cilostazol in patients with chronic
      tinnitus may mitigate the severity of subjective tinnitus.

PMID- 27716605
TI  - Perception of Consonants in Speech-Shaped Noise among Young and Middle-Aged
      Adults.
AB  - OBJECTIVE: The present study was carried out to compare the consonant perception
      of young and middle-aged adults in quiet and noisy listening conditions.
      MATERIALS AND METHODS: Twenty-nine adults aged between 18 and 55 years old
      participated in the study, and were separated into two groups based on their age:
      Group I, comprising 15 young adults aged between 18 and 40 years old, and Group
      II, comprising 14 middle-aged adults aged between 41 and 55 years old. All the
      participants had normal hearing sensitivity in both ears. RESULTS: Consonant
      perception was better in favorable listening conditions for both young and middle
      aged adults. Comparison of the consonant identification scores of young and
      middle-aged adults showed significantly poorer scores among middle-aged adults in
      both quiet and noisy listening conditions. CONCLUSION: The findings of the
      present study reveal that middle-aged adults have small but significant consonant
      perception difficulties compared to younger adults in quiet and noisy listening
      conditions.

PMID- 27716606
TI  - The Effects of Silicone and Acrylic Ear Mold Materials on Outer Ear Canal
      Resonance Characteristics.
AB  - OBJECTIVES: The aim of this study is to investigate the effects of earmolds made
      of silicone and acrylic on outer ear canal resonance characteristics in terms of
      resonance frequency and amplitude measured in a hearing aid fitting. MATERIALS
      AND METHODS: Outer ear canal resonance frequencies and amplitudes in open ears
      and those measured with silicone and acrylic ear molds were obtained from 30
      participants between the ages of 20 and 25 years (average age, 22.0 years; 18
      females and 12 males) with a real ear gain measurement. To observe the changes
      depending on probe tube placement, test-retest variation was investigated in 10
      participants before the study. RESULTS: There was no statistically significant
      difference between open ear canal resonance frequencies and those measured with
      silicone and acrylic earmolds (p>0.05). the silicone earmold resonance amplitude
      values were statistically significantly lower than the open ear canal resonance
      amplitudes when compared to those of the acrylic earmolds (p<0.05). CONCLUSION:
      Depending on the changes occurring in outer ear resonance features as a result of
      earmold materials used in hearing aid fittings, the application of earmolds
      should be done by experienced specialists.

PMID- 27716607
TI  - A Challenge for Cochlear Implantation: Duplicated Internal Auditory Canal.
AB  - Duplication of the internal auditory canal is an uncommon, congenital
      malformation that can be associated with sensorineural hearing loss owing to
      aplasia/hypoplasia of the vestibulocochlear nerve. Only 14 such cases have been
      reported to date. We report the case of a 13-month-old girl with bilateral,
      congenital, sensorineural hearing loss caused by narrow, duplicated internal
      auditory canals and discuss the challenges encountered in the diagnosis and
      treatment of this condition.

PMID- 27716608
TI  - Instability Due to Drug-Induced Vestibulotoxicity.
AB  - OBJECTIVE: The therapeutic use of ototoxic drugs is relatively common,
      particularly in patients with severe diseases. It is likely that disturbances of
      balance in these patients are underestimated by clinicians. MATERIALS AND
      METHODS: The purpose of this study was to identify drugs involved in the
      vestibulotoxic origin of instability in a group of 18 patients. RESULTS: Six
      patients showed both cochlear and vestibular damage, while 12 were affected only
      by posterior labyrinthine damage. Four groups of drugs were identified:
      antibiotics (nine patients), cytostatics (four), anti-tuberculosis medicinal
      products (three), and other drugs (two). Cytostatics were involved in many cases
      studied, a fact scarcely reported before. CONCLUSION: It is important to ensure
      an early diagnosis to prevent ototoxic effects induced by drugs. We propose that
      patients receiving potential ototoxic drugs undergo cochlear and vestibular
      assessments. Further, we recommend that patients with instability undergo
      vestibular rehabilitation.

PMID- 27716609
TI  - Sensorineural Hearing Loss in Congenital Erosive and Vesicular Dermatosis.

PMID- 27716610
TI  - Chemical Closure of Tympanic Membrane Perforation: Call for Caution.
AB  - Chemical closure of tympanic membrane perforation is a commonly practiced office
      based otological procedure, which is labeled to be effective and safe. In this
      paper, we report a case of a young lady with disastrous complications following
      an attempt of chemical cauterization of her perforated tympanic membrane.

PMID- 27716611
TI  - Chronic Tuberculous Otomastoiditis: A Case Report.
AB  - Worldwide, tuberculosis is a widespread disease, with 8.7 million new cases
      occurring annually. Its etiologic agent, Mycobacterium tuberculosis, essentially
      causes pneumonia. However, this organism affects the middle ear in rare cases,
      accounting for 0.04-0.09% of all chronic middle ear otitis cases in Western
      countries. In this report, we describe the case of a young woman affected by
      tuberculosis of the middle ear. In our experience, empiric therapy was not
      beneficial. Adequate treatment was possible only after obtaining a specific
      diagnosis through a difficult process requiring surgical sampling for culture
      examination. We consider surgical sampling to be mandatory in all cases of
      chronic otitis media that do not respond to prolonged systemic and local
      therapies.

PMID- 27716612
TI  - Clinical audit project in undergraduate medical education curriculum: an
      assessment validation study.
AB  - Objectives: To evaluate the merit of the Clinical Audit Project (CAP) in an
      assessment program for undergraduate medical education using a systematic
      assessment validation framework. Methods: A cross-sectional assessment validation
      study at one medical school in Western Australia, with retrospective qualitative
      analysis of the design, development, implementation and outcomes of the CAP, and
      quantitative analysis of assessment data from four cohorts of medical students
      (2011- 2014). Results: The CAP is fit for purpose with clear external and
      internal alignment to expected medical graduate outcomes.  Substantive validity
      in students' and examiners' response processes is ensured through relevant
      methodological and cognitive processes. Multiple validity features are built-in
      to the design, planning and implementation process of the CAP.  There is evidence
      of high internal consistency reliability of CAP scores (Cronbach's alpha > 0.8)
      and inter-examiner consistency reliability (intra-class correlation>0.7).
      Aggregation of CAP scores is psychometrically sound, with high internal
      consistency indicating one common underlying construct.  Significant but moderate
      correlations between CAP scores and scores from other assessment modalities
      indicate validity of extrapolation and alignment between the CAP and the overall
      target outcomes of medical graduates.  Standard setting, score equating and fair
      decision rules justify consequential validity of CAP scores interpretation and
      use. Conclusions: This study provides evidence demonstrating that the CAP is a
      meaningful and valid component in the assessment program. This systematic
      framework of validation can be adopted for all levels of assessment in medical
      education, from individual assessment modality, to the validation of an
      assessment program as a whole.

PMID- 27716613
TI  - Lipid phosphatase SHIP2 functions as oncogene in colorectal cancer by regulating
      PKB activation.
AB  - Colorectal cancer (CRC) is the second most common cause of cancer-related death,
      encouraging the search for novel therapeutic targets affecting tumor cell
      proliferation and migration. These cellular processes are under tight control of
      two opposing groups of enzymes; kinases and phosphatases. Aberrant activity of
      kinases is observed in many forms of cancer and as phosphatases counteract such
      "oncogenic" kinases, it is generally assumed that phosphatases function as tumor
      suppressors. However, emerging evidence suggests that the lipid phosphatase SH2
      domain-containing 5 inositol phosphatase (SHIP2), encoded by the INPPL1 gene, may
      act as an oncogene. Just like the well-known tumor suppressor gene Phosphatase
      and Tensin Homolog (PTEN) it hydrolyses phosphatidylinositol (3,4,5) triphosphate
      (PI(3,4,5)P3). However, unlike PTEN, the reaction product is PI(3,4)P2, which is
      required for full activation of the downstream protein kinase B (PKB/Akt),
      suggesting that SHIP2, in contrast to PTEN, could have a tumor initiating role
      through PKB activation. In this work, we investigated the role of SHIP2 in
      colorectal cancer. We found that SHIP2 and INPPL1 expression is increased in
      colorectal cancer tissue in comparison to adjacent normal tissue, and this is
      correlated with decreased patient survival. Moreover, SHIP2 is more active in
      colorectal cancer tissue, suggesting that SHIP2 can induce oncogenesis in colonic
      epithelial cells. Furthermore, in vitro experiments performed on colorectal
      cancer cell lines shows an oncogenic role for SHIP2, by enhancing
      chemoresistance, cell migration, and cell invasion. Together, these data indicate
      that SHIP2 expression contributes to the malignant potential of colorectal
      cancer, providing a possible target in the fight against this devastating
      disease.

PMID- 27716614
TI  - TNF induced cleavage of HSP90 by cathepsin D potentiates apoptotic cell death.
AB  - During apoptosis induction by TNF, the extrinsic and intrinsic apoptosis pathways
      converge at the lysosomal-mitochondrial interface. Earlier studies showed that
      the lysosomal aspartic protease Cathepsin D (CtsD) cleaves Bid to tBid, resulting
      in the amplification of the initial apoptotic cascade via mitochondrial outer
      membrane permeabilization (MOMP).The goal of this study was to identify further
      targets for CtsD that might be involved in activation upon death receptor
      ligation. Using a proteomics screen, we identified the heat shock protein 90
      (HSP90) to be cleaved by CtsD after stimulation of U937 or other cell lines with
      TNF, FasL and TRAIL. HSP90 cleavage corresponded to apoptosis sensitivity of the
      cell lines to the different stimuli. After mutation of the cleavage site, HSP90
      partially prevented apoptosis induction in U937 and Jurkat cells. Overexpression
      of the cleavage fragments in U937 and Jurkat cells showed no effect on apoptosis,
      excluding a direct pro-apoptotic function of these fragments. Pharmacological
      inhibition of HSP90 with 17AAG boosted ligand mediated apoptosis by enhancing Bid
      cleavage and caspase-9 activation. Together, we demonstrated that HSP90 plays an
      anti-apoptotic role in death receptor signalling and that CtsD-mediated cleavage
      of HSP90 sensitizes cells for apoptosis. These findings identify HSP90 as a
      potential target for cancer therapy in combination with death ligands (e.g. TNF
      or TRAIL).

PMID- 27716615
TI  - PITX2 and PANCR DNA methylation predicts overall survival in patients with head
      and neck squamous cell carcinoma.
AB  - BACKGROUND: Squamous cell carcinoma of the head and neck region (HNSCC) is a
      common malignant disease accompanied by a high risk of local or distant
      recurrence after curative-intent treatment. Biomarkers that allow for the
      prediction of disease outcome can guide clinicians with respect to treatment and
      surveillance strategies. Here, the methylation status of PITX2 and an adjacent
      lncRNA (PANCR) were evaluated for their ability to predict overall survival in
      HNSCC patients. RESULTS: PITX2 hypermethylation was associated with a better
      overall survival (hazard ratio, HR = 0.51, 95%CI: 0.35-0.74, p<0.001), while
      PANCR hypermethylation was significantly associated with an increased risk of
      death (HR = 1.64, 95%CI: 1.12-2.39, p=0.010). METHODS: Quantitative, methylation
      specific real-time PCR assays for PITX2 and PANCR were employed to measure
      bisulfite-converted DNA from formalin-fixed, paraffin-embedded (FFPE) tissues in
      a cohort of 399 patients with localized or locally advanced HNSCC who received
      curative-intent treatment (surgery with optional adjuvant radiochemotherapy or
      definite radiochemotherapy). CONCLUSIONS: PITX2 and PANCR methylation status were
      shown to be independent predictors for overall survival in HNSCC patients. Tissue
      based methylation testing could therefore potentially be employed to identify
      patients with a high risk for death who might benefit from a more radical or
      alternative treatment.

PMID- 27716616
TI  - Ran GTPase promotes cancer progression via Met recepto-rmediated downstream
      signaling.
AB  - It has been shown previously that cancer cells with an activated oncogenic
      pathway, including Met activation, require Ran for growth and survival.Here, we
      show that knockdown of Ran leads to a reduction of Met receptor expression in
      several breast and lung cancer cell lines. This, in turn suppressed HGF
      expression and the Met-mediated activation of the Akt pathway, as well as cell
      adhesion, migration, and invasion. In a cell line model where Met amplification
      has previously been shown to contribute to gefitinib resistance, Ran knockdown
      sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2
      phosphorylation and consequently reduced cell proliferation. We further
      demonstrate that Met reduction-mediated by knockdown of Ran, occurs at the post
      transcriptional level, probably via a matrix metalloproteinase. Moreover, the
      level of immunoreactive Ran and Met are positively associated in human breast
      cancer specimens, suggesting that a high level of Ran may be a pre-requisite for
      Met overexpression. Interestingly, a high level of immunoreactive Ran dictates
      the prognostic significance of Met, indicating that the co-overexpression of Met
      and Ran may be associated with cancer progression and could be used in
      combination as a prognostic indicator.

PMID- 27716617
TI  - Matrix metalloproteinase-13 refines pathological staging of precancerous
      colorectal lesions.
AB  - An exact classification of precancerous stages of colorectal polyps might improve
      therapy and patients' outcome. Here we investigate the association between grade
      of dysplasia and Matrix metalloproteinase-13 (MMP-13) expression in 137 biopsies
      from patients with cancerous and non-cancerous colorectal adenomas. A
      reproducible staining procedure for histologic MMP-13 analysis in routinely fixed
      colorectal biopsy specimens has been established. A newly adopted immunoreactive
      scoring system for MMP-13 was demonstrated as reliable readout.The strength of
      the association between pathologic stage and immunoreactive MMP-13 scoring
      emphasizes its eligibility for diagnosis in precancerous colorectal lesions.

PMID- 27716618
TI  - Prognostic significance of AMPK in human malignancies: A meta-analysis.
AB  - BACKGROUND: AMPK is a well-investigated kinase mediating cellular metabolism and
      stress responses. However, its indicative role in survival prognosis remains ill
      defined. Therefore we performed this meta-analysis in order to clarify the
      prognostic impact of AMPK expression in human malignancies. METHODS: Literatures
      were retrieved via searching databases of PubMed, Web of Science, Embase and
      Cochrane Library. Studies comparing the prognostic significance between different
      AMPK levels among human malignancies were included into the pooled analysis. The
      statistical procedures were conducted by Review Manager 5.3 and the effect size
      was displayed by model of odds ratio. Subgroup analyses were additionally
      implemented to disclose the potential confounding elements. The outcome stability
      was examined by sensitivity analysis, and both Begg's test and Egger's test were
      utilized to detect the publication bias across the included studies. RESULTS: 21
      retrospective cohorts were eventually obtained with a total sample-size of 9987
      participants. Patients with higher AMPK expression had better outcomes of 3-year
      overall survival (P<0.0001), 5-year overall survival (P<0.0001), 10-year overall
      survival (P<0.0001), 3-year disease free survival (P<0.0001), 5-year disease free
      survival (P=0.002) and 10-year disease free survival (P=0.0004). Moreover, the
      majority of subgroup results also verified the favorably prognostic significance
      of AMPK over-expression. The outcome stability was confirmed by sensitivity
      analysis. Results of Begg's (P=0.76) and Egger's test (P=0.09) suggested that
      there was no publication bias within the included trials. CONCLUSIONS: Higher
      expression of AMPK significantly indicates better prognosis in human
      malignancies.

PMID- 27716619
TI  - Alpha fetoprotein antagonises benzyl isothiocyanate inhibition of the malignant
      behaviors of hepatocellular carcinoma cells.
AB  - Benzyl isothiocyanate (BITC) is a dietary isothiocyanate derived from cruciferous
      vegetables. Recent studies showed that BITC inhibited the growth of many cancer
      cells, including hepatocellular carcinoma (HCC) cells. Alpha-fetoprotein (AFP) is
      a important molecule for promoting progression of HCC, in the present
      investigation, we explore the influence of AFP on the role of BITC in the
      malignant behaviours of HCC cells, and the potential underlying mechanisms. We
      found thatBITC inhibited viability, migration, invasion and induced apoptosis of
      human liver cancer cell lines, Bel 7402(AFP producer) and HLE(non-AFP producer)
      cells in vitro. The role of BITC involve in promoting actived-caspase-3 and PARP
      1 expression, and enhancing caspase-3 activity but decreasing MMP-2/9, survivin
      and CXCR4 expression. AFP antagonized the effect of BITC. This study suggests
      that BITC induced significant reductions in the viability of HCC cell lines. BITC
      may activate caspase-3 signal and inhibit the expression of growth- and
      metastasis-related proteins; AFP is an pivotal molecule for the HCC chemo
      resistance of BITC.

PMID- 27716621
TI  - Hypoxia-induced CCL28 promotes recruitment of regulatory T cells and tumor growth
      in liver cancer.
AB  - Tumor cells craft microenvironment to overcome growth disadvantages and adjust to
      escape the immunosurveillance during tumorigenesis and metastasis. The evolving
      adaption to the changing microenvironment is exemplified by the development of
      strategies to deal with hypoxia resulted from fast proliferation of the tumor
      cells. In this study, we found that hypoxia hepatocellular carcinoma (HCC) cells
      recruited Regulatory T cells (Tregs) and expressed more Chemokine (C-C motif)
      ligand 28 (CCL28). Deletion of CCL28 inhibited Treg recruitment. Furthermore,
      overexpression of CCL28 promoted tumor growth and Treg infiltration in vivo.
      Enhanced angiogenesis and VEGF expression was also observed. Moreover, inhibition
      of HIF1alpha reversed hypoxia-induced CCL28 upregulation. Taken together, our
      results demonstrate that HCC recruits Tregs to promote angiogenesis under hypoxic
      condition by upregulating CCL28 expression. These findings establish a link
      between Tregs and hypoxia in HCC growth and may provide a new potential
      therapeutic target for treating HCC.

PMID- 27716620
TI  - Circulating microRNAs found dysregulated in ex-exposed asbestos workers and
      pleural mesothelioma patients as potential new biomarkers.
AB  - Malignant pleural mesothelioma (MPM), a fatal cancer, is an occupational disease
      mostly affecting workers ex-exposed to asbestos fibers. The asbestos, a
      cancerogenic mineral of different chemical composition, was widely employed in
      western Countries in industrial manufactures of different types. MPM may arise
      after a long latency period, up to five decades. MPM is resistant to conventional
      chemo- and radio-therapies. Altogether, these data indicate that the
      identification of new and specific markers are of a paramount importance for an
      early diagnosis and treatment of MPM. In recent years, microRNAs expression was
      found dysregulated in patients, both in cancer cells and sera, affected by tumors
      of different histotypes, including MPM. Cell and circulanting microRNAs, found to
      be dysregulated in this neoplasia, were proposed as new biomarkers. It has been
      reported that circulating microRNAs are stable in biological fluids and could be
      employed as potential MPM biomarkers. In this investigation, circulating
      microRNAs (miR) from serum samples of MPM patients and workers ex-exposed to
      asbestos fibers (WEA) and healthy subjects (HS) were comparatively analyzed by
      microarray and RT-qPCR technologies. Our results allowed (i) to select MiR-3665,
      an endogenous stable microRNA, as the internal control to quantify in our
      analyses circulating miRNAs; to detect (ii) miR-197-3p, miR-1281 and miR 32-3p up
      regulated in MPM compared to HS; (iii) miR-197-3p and miR-32-3p up-regulated in
      MPM compared to WEA; (iv) miR-1281 up-regulated in both MPM and WEA compared to
      HS. In conclusion, three circulating up-regulated microRNAs, i.e. miR-197-3p, miR
      1281 and miR-32-3p are proposed as potential new MPM biomarkers.

PMID- 27716622
TI  - Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1
      (PD-L1) antibody.
AB  - Near Infrared-Photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment
      that employs an antibody-photo-absorber conjugate (APC). Programmed cell death
      protein-1 ligand (PD-L1) is emerging as a molecular target. Here, we describe the
      efficacy of NIR-PIT, using fully human IgG1 anti-PD-L1 monoclonal antibody (mAb),
      avelumab, conjugated to the photo-absorber, IR700DX, in a PD-L1 expressing H441
      cell line, papillary adenocarcinoma of lung. Avelumab-IR700 showed specific
      binding and cell-specific killing was observed after exposure of the cells to NIR
      in vitro. In the in vivo study, avelumab-IR700 showed high tumor accumulation and
      high tumor-background ratio. Tumor-bearing mice were separated into 4 groups: (1)
      no treatment; (2) 100 MUg of avelumab-IR700 i.v.; (3) NIR light exposure only,
      NIR light was administered; (4) 100 MUg of avelumab-IR700 i.v., NIR light was
      administered. Tumor growth was significantly inhibited by NIR-PIT treatment
      compared with the other groups (p < 0.001), and significantly prolonged survival
      was achieved (p < 0.01 vs other groups). In conclusion, the anti-PD-L1 antibody,
      avelumab, is suitable as an APC for NIR-PIT. Furthermore, NIR-PIT with avelumab
      IR700 is a promising candidate of the treatment of PD-L1-expressing tumors that
      could be readily translated to humans.

PMID- 27716623
TI  - Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells.
AB  - Local acidosis is a common feature of allergic, vascular, autoimmune, and cancer
      diseases. However, few studies have addressed the effect of extracellular pH on
      the immune response. Here, we analyzed whether low pH could modulate complement
      dependent cytotoxicity (CDC) against IgG-coated cells. Using human serum as a
      complement source, we found that extracellular pH values of 5.5 and 6.0 strongly
      inhibit CDC against either B lymphoblast cell lines coated with the chimeric anti
      CD20 mAb rituximab or PBMCs coated with the humanized anti-CD52 mAb alemtuzumab.
      Suppression of CDC by low pH was observed either in cells suspended in culture
      medium or in whole blood assays. Interestingly, not only CDC against IgG-coated
      cells, but also the activation of the complement system induced by the
      alternative and lectin pathways was prevented by low pH. Tumor-targeting mAbs
      represent one of the most successful tools for cancer therapy, however, the use
      of mAb monotherapy has only modest effects on solid tumors. Our present results
      suggest that severe acidosis, a hallmark of solid tumors, might impair complement
      mediated tumor destruction directed by mAb.

PMID- 27716625
TI  - Lumbar puncture-administered resveratrol inhibits STAT3 activation, enhancing
      autophagy and apoptosis in orthotopic rat glioblastomas.
AB  - Trans-resveratrol suppresses glioblastoma growth in vitro, but its effects on
      intracranial glioblastomas remain untested. Resveratrol crosses the blood-brain
      barrier, and lumbar puncture (LP) greatly increases its bioavailability in rat
      brains; therefore, we investigated the effectiveness of LP-administered
      resveratrol on orthotopic rat glioblastomas. Twenty-four tumor-bearing rats were
      separated into two groups: Group 1 receiving 100 MUl saline containing 0.3% DMSO
      and Group 2 receiving 100 MUl resveratrol (300 MUM). Treatments started 3 days
      after transplantation in 2-day intervals until death. Intracranial drug
      availabilities, tumor sizes, average life spans and the impacts on STAT3
      signaling, apoptosis and autophagy rates were evaluated. MRI imaging revealed
      that average tumor size in the LP group (495.8 +/- 22.3 mm2) was smaller than the
      control groups (810.3 +/- 56.4 mm2; P<0.05). The mean survival time in the LP
      group (22.2 +/- 2.1 d) was longer than control animals (16.0 +/- 1.8 d; P<0.05).
      LP resveratrol-treated glioblastomas showed less Cyclin D1 staining, enhanced
      autophagy with up-regulated LC3 and Beclin1 expression, and widely distributed
      apoptotic foci around tumor capillaries with suppressed STAT3 expression and
      nuclear translocation. In conclusion, LP-delivered resveratrol efficiently
      inhibited orthotopic rat glioblastoma growth by inactivating STAT3 signaling and
      enhancing autophagy and apoptosis.

PMID- 27716624
TI  - Targeting the hexosamine biosynthetic pathway and O-linked N-acetylglucosamine
      cycling for therapeutic and imaging capabilities in diffuse large B-cell
      lymphoma.
AB  - The hexosamine biosynthetic pathway (HBP) requires two key nutrients glucose and
      glutamine for O-linked N-acetylglucosamine (O-GlcNAc) cycling, a post
      translational protein modification that adds GlcNAc to nuclear and cytoplasmic
      proteins. Increased GlcNAc has been linked to regulatory factors involved in
      cancer cell growth and survival. However, the biological significance of GlcNAc
      in diffuse large B-cell lymphoma (DLBCL) is not well defined. This study is the
      first to show that both the substrate and the endpoint O-GlcNAc transferase (OGT)
      enzyme of the HBP were highly expressed in DLBCL cell lines and in patient tumors
      compared with normal B-lymphocytes. Notably, high OGT mRNA levels were associated
      with poor survival of DLBCL patients. Targeting OGT via small interference RNA in
      DLBCL cells inhibited activation of GlcNAc, nuclear factor kappa B (NF-kappaB),
      and nuclear factor of activated T-cells 1 (NFATc1), as well as cell growth.
      Depleting both glucose and glutamine in DLBCL cells or treating them with an HBP
      inhibitor (azaserine) diminished O-GlcNAc protein substrate, inhibited
      constitutive NF-kappaB and NFATc1 activation, and induced G0/G1 cell-cycle arrest
      and apoptosis. Replenishing glucose-and glutamine-deprived DLBCL cells with a
      synthetic glucose analog (ethylenedicysteine-N-acetylglucosamine [ECG]) reversed
      these phenotypes. Finally, we showed in both in vitro and in vivo murine models
      that DLBCL cells easily take up radiolabeled technetium-99m-ECG conjugate. These
      findings suggest that targeting the HBP has therapeutic relevance for DLBCL and
      underscores the imaging potential of the glucosamine analog ECG in DLBCL.

PMID- 27716626
TI  - Secretory leukoprotease inhibitor is required for efficient quercetin-mediated
      suppression of TNFalpha secretion.
AB  - Dendritic cells (DCs) are professional antigen presenting cells (APCs) that in
      response to microbial infections generate long-lasting adaptive immune response.
      Following microbial uptake, DCs undergo a cascade of cellular differentiation
      that ultimately leads to "mature" DCs. Mature DCs produce a variety of
      inflammatory cytokines, including tumor necrosis factor-alpha (TNFbeta) a key
      cytokine for the inflammatory cascade. In numerous studies, polyphenols,
      including quercetin, demonstrated their ability to suppress TNFalpha secretion
      and protect from the onset of chronic inflammatory disorders. We show that murine
      bone marrow derived DCs express Slpi following quercetin exposure. Slpi is known
      to suppress LPS mediated NFkappaB activation, thus, it was hypothesized that its
      expression could be the key step for polyphenol induced inflammatory suppression.
      Slpi-KO DCs poorly respond to quercetin administration failing to reduce TNFalpha
      secretion in response to quercetin exposure. Supernatant from quercetin exposed
      DCs could also reduce LPS-mediated TNFalpha secretion by unrelated DCs, but this
      property is lost using an anti-Slpi antibody. In vivo, oral administration of
      quercetin is able to induce Slpi expression. Human biopsies from inflamed tract
      of the intestine reveal the presence of numerous SLPI+ cells and the expression
      level could be further increased by quercetin administration. We propose that
      quercetin induces Slpi expression that in turn reduces the inflammatory response.
      Our data encourages the development of nutritional strategies to improve the
      efficiency of current therapies for intestinal chronic inflammatory syndrome and
      reduce the risks of colorectal cancer development.

PMID- 27716627
TI  - Precise ERBB2 copy number assessment in breast cancer by means of molecular
      inversion probe array analysis.
AB  - HER2/ERBB2 amplification/overexpression determines the eligibility of breast
      cancer patients to HER2-targeted therapy. This study evaluates the agreement
      between ERBB2 copy number assessment by fluorescence in situ hybridization, a
      standard method recommended by the American Society of Clinical Oncology/College
      of American Pathologists (ASCO/CAP), and newly available DNA extraction-based
      methods. A series of n=29 formalin-fixed paraffin-embedded breast cancers were
      subjected to ERBB2 copy number assessment by fluorescence in situ hybridization
      (FISH, Vysis, Abbott). Following macrodissection of invasive breast cancer tissue
      and DNA extraction, ERBB2 copy number was also determined by molecular inversion
      probe array analysis (MIP, OncoScan, Affymetrix) and next generation sequencing
      combined with normalized amplicon coverage analysis (NGS/NAC, AmpliSeq, Ion
      Torrent). ERBB2 copy number values obtained by MIP or NGS/NAC were tightly
      correlated with ERBB2 copy number values obtained by conventional FISH (rs =
      0.940 and rs = 0.894, P < 0.001). Using ASCO/CAP guideline-conform thresholds for
      categorization of breast cancers as HER2-negative, equivocal or positive, nearly
      perfect concordance was observed for HER2 classification by FISH and MIP (93%
      concordant classifications, kappa = 0.87). Substantial concordance was observed
      for FISH and NGS/NAC (83% concordant classifications, kappa = 0.62). In
      conclusion, MIP facilitates precise ERBB2 copy number detection and should be
      considered as an ancillary method for clinical HER2 testing.

PMID- 27716628
TI  - A comparison of different bioinks for 3D bioprinting of fibrocartilage and
      hyaline cartilage.
AB  - Cartilage is a dense connective tissue with limited self-repair capabilities.
      Mesenchymal stem cell (MSC) laden hydrogels are commonly used for fibrocartilage
      and articular cartilage tissue engineering, however they typically lack the
      mechanical integrity for implantation into high load bearing environments. This
      has led to increased interested in 3D bioprinting of cell laden hydrogel bioinks
      reinforced with stiffer polymer fibres. The objective of this study was to
      compare a range of commonly used hydrogel bioinks (agarose, alginate, GelMA and
      BioINKTM) for their printing properties and capacity to support the development
      of either hyaline cartilage or fibrocartilage in vitro. Each hydrogel was seeded
      with MSCs, cultured for 28 days in the presence of TGF-beta3 and then analysed
      for markers indicative of differentiation towards either a fibrocartilaginous or
      hyaline cartilage-like phenotype. Alginate and agarose hydrogels best supported
      the development of hyaline-like cartilage, as evident by the development of a
      tissue staining predominantly for type II collagen. In contrast, GelMA and
      BioINKTM (a PEGMA based hydrogel) supported the development of a more
      fibrocartilage-like tissue, as evident by the development of a tissue containing
      both type I and type II collagen. GelMA demonstrated superior printability,
      generating structures with greater fidelity, followed by the alginate and agarose
      bioinks. High levels of MSC viability were observed in all bioinks post-printing
      (~80%). Finally we demonstrate that it is possible to engineer mechanically
      reinforced hydrogels with high cell viability by co-depositing a hydrogel bioink
      with polycaprolactone filaments, generating composites with bulk compressive
      moduli comparable to articular cartilage. This study demonstrates the importance
      of the choice of bioink when bioprinting different cartilaginous tissues for
      musculoskeletal applications.

PMID- 27716629
TI  - Ethical considerations in the translation of regenerative biofabrication
      technologies into clinic and society.
AB  - Biofabrication technologies have the potential to improve healthcare by providing
      highly advanced and personalized biomedical products for research, treatment and
      prevention. As the combining of emerging techniques and integrating various
      biological and synthetic components becomes increasingly complex, it is important
      that relevant stakeholders anticipate the translation of biofabricated 3D tissue
      products into patients and society. Ethics is sometimes regarded as a brake on
      scientific progress, yet from our perspective, ethics in parallel with research
      anticipates societal impacts of emerging technologies and stimulates responsible
      innovation. For the ethical assessment, the biofabrication field benefits from
      similarities to regenerative medicine and an increasing ethical awareness in the
      development of tissue-engineered products. However, the novelty of the technology
      itself, the increase in attainable structural complexity, and the potential for
      automation and personalization are distinguishing facets of biofabrication that
      call for a specific exploration of the ethics of biofabrication. This review aims
      to highlight important points of existing ethical discussions, as well as to call
      attention to emerging issues specific to 3D biofabrication in bench and bedside
      research and the translation to society.

PMID- 27716630
TI  - Evaluation of 3D printed PCL/PLGA/beta-TCP versus collagen membranes for guided
      bone regeneration in a beagle implant model.
AB  - Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/beta
      tricalcium phosphate (PCL/PLGA/beta-TCP) membranes with the widely used collagen
      membranes for guided bone regeneration (GBR) in beagle implant models. For
      mechanical property comparison in dry and wet conditions and cytocompatibility
      determination, we analyzed the rate and pattern of cell proliferation of seeded
      fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning
      electron microscopy. Osteogenic differentiation was verified using alizarin red S
      staining. At 8 weeks following implantation in vivo using beagle dogs, computed
      tomography and histological analyses were performed after sacrifice. Cell
      proliferation rates in vitro indicated that early cell attachment was higher in
      collagen than in PCL/PLGA/beta-TCP membranes; however, the difference subsided by
      day 7. Similar outcomes were found for osteogenic differentiation, with
      approximately 2.5 times greater staining in collagen than PCL/PLGA/beta-TCP, but
      without significant difference by day 14. In vivo, bone regeneration in the
      defect area, represented by new bone formation and bone-to-implant contact,
      paralleled those associated with collagen membranes. However, tensile testing
      revealed that whereas the PCL/PLGA/beta-TCP membrane mechanical properties were
      conserved in both wet and dry states, the tensile property of collagen was
      reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo
      that PCL/PLGA/beta-TCP membranes have similar levels of biocompatibility and bone
      regeneration as collagen membranes. In particular, considering that GBR is always
      applied to a wet environment (e.g. blood, saliva), we demonstrated that
      PCL/PLGA/beta-TCP membranes maintained their form more reliably than collagen
      membranes in a wet setting, confirming their appropriateness as a GBR membrane.

PMID- 27716631
TI  - Bioactivity of dexamethasone-releasing coatings on polymer/magnesium composites.
AB  - We developed biodegradable polymeric coatings loaded with increasing amounts of
      dexamethasone on composites based on polylactic acid and Mg particles for bone
      repair. Incorporation of Mg particles into the polymeric matrix improves the
      compressive behaviour of the polymer. Mg-containing composites release Mg2+ ions
      into the culture medium and improve mesenchymal stem cell (MSC) viability,
      enhance their osteogenic potential and promote the release of angiogenic factors.
      Dexamethasone-loaded coatings deposited on composites delay Mg2+ ion dissolution
      while releasing controlled amounts of the drug, which are highly dependent on
      initial payload. Release kinetic of dexamethasone from the coatings exhibits a
      fast initial release of the drug followed by a slower secondary release.
      Bioactivity of the released dexamethasone was explored by monitoring dose
      dependent responses of MSCs and macrophages. Biological effects exerted by the
      released drug are similar to those observed in cells treated with solutions of
      the glucocorticoid, indicating that the method employed for inclusion of
      dexamethasone into the coatings does not impair its bioactive behaviour.
      Culturing MSCs on dexamethasone-releasing coatings enhances extracellular matrix
      production and initial induction to osteogenic commitment as a function of drug
      payload. Dexamethasone incorporated into the coatings presents anti-inflammatory
      activity, as shown by the decrease in the production of cytokines and angiogenic
      factors by macrophages and MSCs. Deposition of dexamethasone-releasing coatings
      on polymer/Mg composites appears to be a promising approach to delay composite
      degradation at the early stage of implantation and may be useful to attenuate
      inflammation and adverse foreign body reactions.

PMID- 27716632
TI  - Characterization of Al2O3 optically stimulated luminescence films for 2D
      dosimetry using a 6 MV photon beam.
AB  - This work evaluates the dosimetric properties of newly developed optically
      stimulated luminescence (OSL) films, fabricated with either Al2O3:C or
      Al2O3:C,Mg, using a prototype laser scanning reader, a developed image
      reconstruction algorithm, and a 6 MV therapeutic photon beam. Packages containing
      OSL films (Al2O3:C and Al2O3:C,Mg) and a radiochromic film (Gafchromic EBT3) were
      irradiated using a 6 MV photon beam using different doses, field sizes, with and
      without wedge filter. Dependence on film orientation of the OSL system was also
      tested. Diode-array (MapCHECK) and ionization chamber measurements were performed
      for comparison. The OSLD film doses agreed with the MapCHECK and ionization
      chamber data within the experimental uncertainties (<2% at 1.5 Gy). The system
      background and minimum detectable dose (MDD) were  <0.5 mGy, and the dose
      response was approximately linear from the MDD up to a few grays (the linearity
      correction was  <10% up to ~2-4 Gy), with no saturation up to 30 Gy. The dose
      profiles agreed with those obtained using EBT3 films (analyzed using the triple
      channel method) in the high dose regions of the images. In the low dose regions,
      the dose profiles from the OSLD films were more reproducible than those from the
      EBT3 films. We also demonstrated that the OSL film data are independent on scan
      orientation and field size over the investigated range. The results demonstrate
      the potential of OSLD films for 2D dosimetry, particularly for the
      characterization of small fields, due to their wide dynamic range, linear
      response, resolution and dosimetric properties. The negligible background and
      potential simple calibration make these OSLD films suitable for remote audits.
      The characterization presented here may motivate further commercial development
      of a 2D dosimetry system based on the OSL from Al2O3:C or Al2O3:C,Mg.

PMID- 27716633
TI  - 3D printing of photocurable poly(glycerol sebacate) elastomers.
AB  - Three-dimensional (3D) printed scaffolds have great potential in biomedicine;
      however, it is important that we are able to design such scaffolds with a range
      of diverse properties towards specific applications. Here, we report the
      extrusion-based 3D printing of biodegradable and photocurable acrylated
      polyglycerol sebacate (Acr-PGS) to fabricate scaffolds with elastic properties.
      Two Acr-PGS macromers were synthesized with varied molecular weights and
      viscosity, which were then blended to obtain photocurable macromer inks with a
      range of viscosities. The quality of extruded and photocured scaffolds was
      dependent on the initial ink viscosity, with flow of printed material resulting
      in a loss of structural resolution or sample breaking observed with too low or
      too high viscosity inks, respectively. However, scaffolds with high print
      resolution and up to ten layers were fabricated with an optimal ink viscosity.
      The mechanical properties of printed scaffolds were dependent on printing
      density, where the scaffolds with lower printing density possessed lower moduli
      and failure properties than higher density scaffolds. The 3D printed scaffolds
      supported the culture of 3T3 fibroblasts and both spreading and proliferation
      were observed, indicating that 3D printed Acr-PGS scaffolds are cytocompatible.
      These results demonstrate that Acr-PGS is a promising material for the
      fabrication of elastomeric scaffolds for biomedical applications.

PMID- 27716634
TI  - Stochastic simulation tools and continuum models for describing two-dimensional
      collective cell spreading with universal growth functions.
AB  - Two-dimensional collective cell migration assays are used to study cancer and
      tissue repair. These assays involve combined cell migration and cell
      proliferation processes, both of which are modulated by cell-to-cell crowding.
      Previous discrete models of collective cell migration assays involve a nearest
      neighbour proliferation mechanism where crowding effects are incorporated by
      aborting potential proliferation events if the randomly chosen target site is
      occupied. There are two limitations of this traditional approach: (i) it seems
      unreasonable to abort a potential proliferation event based on the occupancy of a
      single, randomly chosen target site; and, (ii) the continuum limit description of
      this mechanism leads to the standard logistic growth function, but some
      experimental evidence suggests that cells do not always proliferate logistically.
      Motivated by these observations, we introduce a generalised proliferation
      mechanism which allows non-nearest neighbour proliferation events to take place
      over a template of [Formula: see text] concentric rings of lattice sites.
      Further, the decision to abort potential proliferation events is made using a
      crowding function, f(C), which accounts for the density of agents within a group
      of sites rather than dealing with the occupancy of a single randomly chosen site.
      Analysing the continuum limit description of the stochastic model shows that the
      standard logistic source term, [Formula: see text], where lambda is the
      proliferation rate, is generalised to a universal growth function, [Formula: see
      text]. Comparing the solution of the continuum description with averaged
      simulation data indicates that the continuum model performs well for many choices
      of f(C) and r. For nonlinear f(C), the quality of the continuum-discrete match
      increases with r.

PMID- 27716635
TI  - Roberts Prize for the best paper published in 2015.

PMID- 27716636
TI  - Evaluation of amorphous magnesium phosphate (AMP) based non-exothermic orthopedic
      cements.
AB  - This paper reports for the first time the development of a biodegradable, non
      exothermic, self-setting orthopedic cement composition based on amorphous
      magnesium phosphate (AMP). The occurrence of undesirable exothermic reactions was
      avoided through using AMP as the solid precursor. The phenomenon of self-setting
      with optimum rheology is achieved by incorporating a water soluble
      biocompatible/biodegradable polymer, polyvinyl alcohol (PVA). Additionally, PVA
      enables a controlled growth of the final phase via a biomimetic process. The AMP
      powder was synthesized using a precipitation method. The powder, when in contact
      with the aqueous PVA solution, forms a putty resulting in a nanocrystalline
      magnesium phosphate phase of cattiite. The as-prepared cement compositions were
      evaluated for setting times, exothermicity, compressive strength, biodegradation,
      and microstructural features before and after soaking in SBF, and in vitro
      cytocompatibility. Since cattiite is relatively unexplored in the literature, a
      first time evaluation reveals that it is cytocompatible, just like the other
      phases in the MgO-P2O5 (Mg-P) system. The cement composition prepared with 15%
      PVA in an aqueous medium achieved clinically relevant setting times, mechanical
      properties, and biodegradation. Simulated body fluid (SBF) soaking resulted in
      coating of bobierrite onto the cement particle surfaces.

PMID- 27716637
TI  - Adaptation of the microdosimetric kinetic model to hypoxia.
AB  - Ion beams present a potential advantage in terms of treatment of lesions with
      hypoxic regions. In order to use this potential, it is important to accurately
      model the cell survival of oxic as well as hypoxic cells. In this work, an
      adaptation of the microdosimetric kinetic (MK) model making it possible to
      account for cell hypoxia is presented. The adaptation relies on the modification
      of damage quantity (double strand breaks and more complex lesions) due to the
      radiation. Model parameters such as domain size and nucleus size are then adapted
      through a fitting procedure. We applied this approach to two cell lines, HSG and
      V79 for helium, carbon and neon ions. A similar behaviour of the parameters was
      found for the two cell lines, namely a reduction of the domain size and an
      increase in the sensitive nuclear volume of hypoxic cells compared to those of
      oxic cells. In terms of oxygen enhancement ratio (OER), the experimental data
      behaviour can be reproduced, including dependence on particle type at the same
      linear energy transfer (LET). Errors on the cell survival prediction are of the
      same order of magnitude than for the original MK model. Our adaptation makes it
      possible to account for hypoxia without modelling the OER as a function of the
      LET of the particles, but directly accounting for hypoxic cell survival data.

PMID- 27716638
TI  - Expanding the scale of molecular biophysics.
AB  - Here, I argue that some of the secrets of complex biological function rely on
      assemblies of many heterogeneous proteins that together enable sophisticated
      sensing and actuating processes. Evolution seems to delight in making these
      structures and in continually elaborating upon their capabilities. Developing
      tools that can go beyond the few protein limit, both on the experimental frontier
      and from a theoretical, conceptual framework, should be an extremely high
      priority for the next generation of molecular biophysicists.

PMID- 27716639
TI  - Depth-resolved 3D visualization of coronary microvasculature with optical
      microangiography.
AB  - In this study, we propose a novel implementation of optical coherence tomography
      based angiography combined with ex vivo perfusion of fixed hearts to visualize
      coronary microvascular structure and function. The extracorporeal perfusion of
      Intralipid solution allows depth-resolved angiographic imaging, control of
      perfusion pressure, and high-resolution optical microangiography. The imaging
      technique offers new opportunities for microcirculation research in the heart,
      which has been challenging due to motion artifacts and the lack of independent
      control of pressure and flow. With the ability to precisely quantify structural
      and functional features, this imaging platform has broad potential for the study
      of the pathophysiology of microvasculature in the heart as well as other organs.

PMID- 27716640
TI  - A promising new mechanism of ionizing radiation detection for positron emission
      tomography: modulation of optical properties.
AB  - Using conventional scintillation detection, the fundamental limit in positron
      emission tomography (PET) time resolution is strongly dependent on the inherent
      temporal variances generated during the scintillation process, yielding an
      intrinsic physical limit for the coincidence time resolution of around 100 ps. On
      the other hand, modulation mechanisms of the optical properties of a material
      exploited in the optical telecommunications industry can be orders of magnitude
      faster. In this paper we borrow from the concept of optics pump-probe measurement
      to for the first time study whether ionizing radiation can produce modulations of
      optical properties, which can be utilized as a novel method for radiation
      detection. We show that a refractive index modulation of approximately [Formula:
      see text] is induced by interactions in a cadmium telluride (CdTe) crystal from a
      511 keV photon source. Furthermore, using additional radionuclide sources, we
      show that the amplitude of the optical modulation signal varies linearly with
      both the detected event rate and average photon energy of the radiation source.

PMID- 27716641
TI  - A versatile method for combining different biopolymers in a core/shell fashion by
      3D plotting to achieve mechanically robust constructs.
AB  - Three-dimensional extrusion of two different biomaterials in a core/shell (c/s)
      fashion has gained much interest in the last couple of years as it allows for
      fabricating constructs with novel and interesting properties. We now demonstrate
      that combining high concentrated (16.7 wt%) alginate hydrogels as shell material
      with low concentrated, soft biopolymer hydrogels as core leads to mechanically
      stable and robust 3D scaffolds. Alginate, chitosan, gellan gum, gelatin and
      collagen hydrogels were utilized successfully as core materials-hydrogels which
      are too soft for 3D plotting of open-porous structures without an additional
      mechanical support. The respective c/s scaffolds were characterized concerning
      their morphology, mechanical properties and swelling behavior. It could be shown
      that core as well as shell part can be loaded with growth factors and that the
      release depends on core composition and shell thickness. Neither the plotting
      process nor the crosslinking with 1M CaCl2 denatured the proteins. When core and
      shell were loaded with different growth factors (VEGF and BMP-2, respectively) a
      dual release was achieved. Finally, live human endothelial cells were integrated
      in the core material, demonstrating that this new strategy can be used for
      bioprinting purposes as well.

PMID- 27716642
TI  - Automatic exposure control calibration and optimisation for abdomen, pelvis and
      lumbar spine imaging with an Agfa computed radiography system.
AB  - The use of three physical image quality metrics, signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR) and mean effective noise equivalent quanta (eNEQm)
      have recently been examined by our group for their appropriateness in the
      calibration of an automatic exposure control (AEC) device for chest radiography
      with an Agfa computed radiography (CR) imaging system. This study uses the same
      methodology but investigates AEC calibration for abdomen, pelvis and spine CR
      imaging. AEC calibration curves were derived using a simple uniform phantom
      (equivalent to 20 cm water) to ensure each metric was held constant across the
      tube voltage range. Each curve was assessed for its clinical appropriateness by
      generating computer simulated abdomen, pelvis and spine images (created from real
      patient CT datasets) with appropriate detector air kermas for each tube voltage,
      and grading these against reference images which were reconstructed at detector
      air kermas correct for the constant detector dose indicator (DDI) curve currently
      programmed into the AEC device. All simulated images contained clinically
      realistic projected anatomy and were scored by experienced image evaluators.
      Constant DDI and CNR curves did not provide optimized performance but constant
      eNEQm and SNR did, with the latter being the preferred calibration metric given
      that it is easier to measure in practice. This result was consistent with the
      previous investigation for chest imaging with AEC devices. Medical physicists may
      therefore use a simple and easily accessible uniform water equivalent phantom to
      measure the SNR image quality metric described here when calibrating AEC devices
      for abdomen, pelvis and spine imaging with Agfa CR systems, in the confidence
      that clinical image quality will be sufficient for the required clinical task.
      However, to ensure appropriate levels of detector air kerma the advice of expert
      image evaluators must be sought.

PMID- 27716643
TI  - Evaluation of the microscopic dose enhancement for nanoparticle-enhanced Auger
      therapy.
AB  - The aim of this study is to investigate the dosimetric characteristics of
      nanoparticle-enhanced Auger therapy. Monte Carlo (MC) simulations were performed
      to assess electron energy spectra and dose enhancement distributions around a
      nanoparticle. In the simulations, two types of nanoparticle structures were
      considered: nanoshell and nanosphere, both of which were assumed to be made of
      one of five elements (Fe, Ag, Gd, Au, and Pt) in various sizes (2-100 nm). Auger
      electron emitting radionuclides (I-125, In-111, and Tc-99m) were simulated within
      a nanoshell or on the surface of a nanosphere. For the most promising combination
      of Au and I-125, the maximum dose enhancement was up to 1.3 and 3.6 for the
      nanoshell and the nanosphere, respectively. The dose enhancement regions were
      restricted within 20-100 nm and 0-30 nm distances from the surface of Au
      nanoshell and nanosphere, respectively. The dose enhancement distributions varied
      with sizes of nanoparticles, nano-elements, and radionuclides and thus should be
      carefully taken into account for biological modeling. If the nanoparticles are
      accumulated in close proximity to the biological target, this new type of
      treatment can deliver an enhanced microscopic dose to the target (e.g. DNA).
      Therefore, we conclude that Auger therapy combined with nanoparticles could have
      the potential to provide a better therapeutic effect than conventional Auger
      therapy alone.

PMID- 27716644
TI  - Influence of pH and ionic strength on electrostatic properties of ferredoxin,
      FNR, and hydrogenase and the rate constants of their interaction.
AB  - Ferredoxin (Fd) protein transfers electrons from photosystem I (PSI) to
      ferredoxin:NADP+-reductase (FNR) in the photosynthetic electron transport chain,
      as well as other metabolic pathways. In some photosynthetic organisms including
      cyanobacteria and green unicellular algae under anaerobic conditions Fd transfers
      electrons not only to FNR but also to hydrogenase-an enzyme which catalyzes
      reduction of atomic hydrogen to H2. One of the questions posed by this
      competitive relationship between proteins is which characteristics of thylakoid
      stroma media allow switching of the electron flow between the linear path PSI-Fd
      FNR-NADP+ and the path PSI-Fd-hydrogenase-H2. The study was conducted using
      direct multiparticle simulation approach. In this method protein molecules are
      considered as individual objects that experience Brownian motion and
      electrostatic interaction with the surrounding media and each other. Using the
      model we studied the effects of pH and ionic strength (I) upon complex formation
      between ferredoxin and FNR and ferredoxin and hydrogenase. We showed that the
      rate constant of Fd-FNR complex formation is constant in a wide range of
      physiologically significant pH values. Therefore it can be argued that regulation
      of FNR activity doesn't involve pH changes in stroma. On the other hand, in the
      model rate constant of Fd-hydrogenase interaction dramatically depends upon pH:
      in the range 7-9 it increases threefold. It may seem that because hydrogenase
      reduces protons it should be more active when pH is acidic. Apparently,
      regulation of hydrogenase's affinity to both her reaction partners (H+ and Fd) is
      carried out by changes in its electrostatic properties. In the dark, the protein
      is inactive and in the light it is activated and starts to interact with both Fd
      and H+. Therefore, we can conclude that in chloroplasts the rate of hydrogen
      production is regulated by pH through the changes in the affinity between
      hydrogenase and ferredoxin.

PMID- 27716645
TI  - How to include the variability of TMS responses in simulations: a speech mapping
      case study.
AB  - When delivered over a specific cortical site, TMS can temporarily disrupt the
      ongoing process in that area. This allows mapping of speech-related areas for
      preoperative evaluation purposes. We numerically explore the observed variability
      of TMS responses during a speech mapping experiment performed with a
      neuronavigation system. We selected four cases with very small perturbations in
      coil position and orientation. In one case (E) a naming error occurred, while in
      the other cases (NEA, B, C) the subject appointed the images as smoothly as
      without TMS. A realistic anisotropic head model was constructed of the subject
      from T1-weighted and diffusion-weighted MRI. The induced electric field
      distributions were computed, associated to the coil parameters retrieved from the
      neuronavigation system. Finally, the membrane potentials along relevant white
      matter fibre tracts, extracted from DTI-based tractography, were computed using a
      compartmental cable equation. While only minor differences could be noticed
      between the induced electric field distributions of the four cases, computing the
      corresponding membrane potentials revealed different subsets of tracts were
      activated. A single tract was activated for all coil positions. Another tract was
      only triggered for case E. NEA induced action potentials in 13 tracts, while NEB
      stimulated 11 tracts and NEC one. The calculated results are certainly sensitive
      to the coil specifications, demonstrating the observed variability in this study.
      However, even though a tract connecting Broca's with Wernicke's area is only
      triggered for the error case, further research is needed on other study cases and
      on refining the neural model with synapses and network connections. Case- and
      subject-specific modelling that includes both electromagnetic fields and neuronal
      activity enables demonstration of the variability in TMS experiments and can
      capture the interaction with complex neural networks.

PMID- 27716646
TI  - Modelling topical photodynamic therapy treatment including the continuous
      production of Protoporphyrin IX.
AB  - Most existing theoretical models of photodynamic therapy (PDT) assume a uniform
      initial distribution of the photosensitive molecule, Protoporphyrin IX (PpIX).
      This is an adequate assumption when the prodrug is systematically administered;
      however for topical PDT this is no longer a valid assumption. Topical application
      and subsequent diffusion of the prodrug results in an inhomogeneous distribution
      of PpIX, especially after short incubation times, prior to light illumination. In
      this work a theoretical simulation of PDT where the PpIX distribution depends on
      the incubation time and the treatment modality is described. Three steps of the
      PpIX production are considered. The first is the distribution of the topically
      applied prodrug, the second in the conversion from the prodrug to PpIX and the
      third is the light distribution which affects the PpIX distribution through
      photobleaching. The light distribution is modelled using a Monte Carlo radiation
      transfer model and indicates treatment depths of around 2 mm during daylight PDT
      and approximately 3 mm during conventional PDT. The results suggest that
      treatment depths are not only limited by the light penetration but also by the
      PpIX distribution.

PMID- 27716647
TI  - Immobilization of salvianolic acid B-loaded chitosan microspheres distributed
      three-dimensionally and homogeneously on the porous surface of hydroxyapatite
      scaffolds.
AB  - Porous hydroxyapatite (HA) scaffolds combined with a drug delivery system have
      attracted much attention for bone tissue engineering. In this study, an easy and
      highly efficient method was developed to immobilize salvianolic acid B (Sal B)
      loaded chitosan (CS) microspheres three dimensionally and homogeneously on the
      surface of HA scaffolds pre-coated with alginate. Porous HA scaffolds were
      prepared via a template-leaching process and CS microspheres (used as drug
      carriers) were fabricated by an emulsion method. To improve adhesion between the
      microspheres and HA scaffolds, alginate was used to pre-coat the porous surface
      of the HA scaffolds. Various concentrations of alginate were used to optimize the
      adhesion of Sal B-loaded CS microspheres to the scaffold surface. During the
      adherence process, coated HA scaffolds were immersed in an aqueous solution
      containing Sal B-loaded CS microspheres, followed by standing or shaking at 37 
      degrees C for a certain time. The results showed that the microspheres were
      solidly and homogeneously distributed on the porous surface of the alginate pre
      coated HA scaffolds via electrostatic interactions. Few microspheres detached
      from the porous surface, even after the HA scaffolds with microspheres were
      treated by shaking in distilled water for as long as 7 d. Compared with the
      static condition, the distribution of Sal B-loaded CS microspheres on the porous
      surface of pre-coated HA scaffolds in the shaken condition was more homogeneous
      and almost unaggregated. Additionally, the compressive strength of the scaffolds
      coated with alginate was obviously improved. The optimal alginate coating
      concentration was 1% (i.e. the microstructure of the porous surfaces of the HA
      scaffolds was almost unchanged). The release profile of Sal B over a 30 d
      immersion found an initial burst release followed by a sustained release. The
      result of cell culture in vitro was that 1% alginate-coated scaffolds with Sal B
      loaded CS microspheres obviously promoted cell proliferation after cell culture
      for 3 and 7 d, and cells were attached and uniformly distributed on the porous
      surface of the scaffolds. The strategy of incorporating drug-loaded microspheres
      with porous HA scaffolds could provide an excellent bone substitute for repair of
      bone tissue defects.

PMID- 27716648
TI  - Enhancing vascularization of a gelatin-based micro-cavitary hydrogel by
      increasing the density of the micro-cavities.
AB  - The transport of nutrients and oxygen by vascular networks into engineered tissue
      constructs is critical to their successful integration into host tissues.
      Hydrogel has achieved some promising results as scaffolds for vascularization.
      However, the vascularization of hydrogel is still constrained by its inherent
      submicron- or nano-sized pores. In this study, two gelatin-based micro-cavitary
      gel (Gel-MCG) constructs with varying densities of micro-cavities were developed
      with a photocrosslinkable gelatin methacrylate (Gel-MA) precursor and porogenic
      gelatin microspheres (MS), and their functions in supporting vascularization
      within hydrogels were evaluated with endothelial progenitor outgrowth cells
      (EPOCs). The increase of cavitary density could enhance the vascularization of
      Gel-MCG constructs. After 14 d of culture in vitro, the vascularization of Gel
      MCG constructs with higher cavitary density was significantly superior to that of
      gelatin spongy control and the fusion of vascularized cavities in the constructs
      could be observed. Further subcutaneous implantation of the Gel-MCG constructs
      with higher cavitary density into nude mice also showed obvious vascular invasion
      from host tissues. Taken together, these results indicate that the increase in
      cavitary density can efficiently facilitate the vascularization of Gel-MCG
      constructs both in vitro and in vivo and that such highly-porous Gel-MCG
      constructs have great potential to be a promising scaffold for the development of
      vascularized tissue constructs.

PMID- 27716649
TI  - Venoarteriolar reflex responses in diabetic patients.
AB  - The aim of this study was to investigate the venoarteriolar reflex (VAR)
      responses in type 1 (T1DM) and type 2 (T2DM) diabetes mellitus (DM) with
      polyneuropathy and to estimate their relationship with age, DM duration, initial
      cutaneous temperature and body mass index. Four groups of subjects were
      investigated: 1st group -20 patients with T1DM; 2nd group -50 patients with T2DM;
      3rd group of 20 healthy subjects with similar age and body mass index (BMI) to
      the T1DM group; 4th group (Control2) of 24 healthy subjects adjusted by age and
      BMI to the T2DM group. The cutaneous perfusions of the big toe pulp were
      monitored as baseline perfusions at a temperature of 32 degrees C in supine and
      sitting position with hanging legs and back in supine position. Loss of
      venoarteriolar reflex responses was established in 75% of T1DM patients, 78% of
      T2DM patients and in none of the investigated healthy controls. Reduced
      venoarteriolar perfusion responses were established in both T1DM and T2DM
      patients with polyneuropathy compared with healthy subjects. Reliable positive
      associations between VAR responses and the age, DM duration and initial cutaneous
      temperature were found.

PMID- 27716650
TI  - Microvascular reactivity to thermal stimulation in patients with diabetes
      mellitus and polyneuropathy.
AB  - The study aimed to investigate local thermally induced microvascular reactivity
      in patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) and
      polyneuropathy and to compare it with healthy controls. A hundred and fourteen
      subjects were investigated divided into 3 groups: 1st group -20 patients with
      T1DM; 2nd group -50 patients with T2DM; 3rd group -44 healthy controls. The skin
      perfusions of the first tiptoe were monitored by laser Doppler flowmetry during
      thermal test. The initial (PUi) and basal perfusions at 32 degrees C (PUb) tended
      to be higher in the DM groups and the PUb of T1DM group was higher compared with
      the healthy subjects. The perfusion responses to heating were attenuated in the
      patients compared with the controls. The calculated vasodilator heat-induced
      indices were significantly lower and the vasoconstrictor indices during relative
      cooling in the recovery period were significantly higher in DM patients related
      to the healthy subjects. The reduced cutaneous microvascular responses to local
      thermal stimulation in the plantar sides of the toes of both T1DM and T2DM
      patients with polyneuropathy were similar to those found by previous studies in
      other investigated sites of glabrous and nonglabrous skin of patients with DM.

PMID- 27716651
TI  - RBC aggregation in dextran solutions can be measured by flow cytometry.
AB  - The impact of macromolecules on RBC aggregation continues to be of interest,
      nevertheless present measurements still have limitations and need improvement. We
      applied flow cytometry to measure RBC aggregation in dextran T500 (Dx500)
      solution. The samples were fixed in the aggregated state by glutaraldehyde. Fixed
      RBC exhibit auto fluorescence, which can be detected by flow cytometry. Single
      cells, doublets, triplets and larger aggregates can be distinguished
      quantitatively and quickly due to the correlation between auto fluorescence
      intensity and number of RBC per measured event. With the increase in
      concentration of Dx500, percentages of all aggregates and bigger aggregates
      increased significantly at concentration of 2%, 4% and 6%, while decreased when
      the concentration reached 8% and 10%. The percentage of bigger aggregates in
      concentration of 4% was higher than that in 2% and 6%. The data of flow cytometry
      was confirmed by microscopic observation and are in good agreement with the
      literature. The method provide additional advantages to the conventional
      measurement of RBC aggregation. It gets the distribution of single cells and
      aggregates as derived from the microscopic observation with hematocrit of
      physiological level. It uses sample volume as 1/5~1/10 as needed in
      sendimentation and photometricmethods.

PMID- 27716652
TI  - Red blood cell distribution width is a survival predictor beyond anemia and Nt
      ProBNP in stable optimally medicated heart failure with reduced ejection fraction
      outpatients.
AB  - BACKGROUND: RDW is an automatic value obtained with the blood count, and
      represents the erythrocytes dimension variation. OBJECTIVE: To evaluate in
      optimally medicated outpatients with heart failure with reduced ejection fraction
      (HFrEF) the RDW prognostic value regarding survival in a multivariable model
      including anemia and Nt-ProBNP. METHODS: 233 consecutive outpatients, LVEF <40%,
      clinically stable were followed-up for 3-years in an HF Unit. End-point was all
      cause death. The RDW categorized according to the tertiles (T1 = <13.9; T2 14
      15.2; T3> = 15.3). Anemia classified according to the WHO criteria. Cox survival
      model adjusted for clinical profile, optimal therapeutic, renal function, Nt
      ProBNP, etiology, atrial fibrillation, and anemia. RESULTS: (1) The 3-years death
      rate was 33.5%, and increased with the RDW tertiles (17.3%; 25%; 61.1%; p <
      0.001). (2) The ROC curve for death associated with RDW (AUC 0.73; p < 0.001);
      (3) The adjusted death risk increased with the tertiles (Hazard-ratio '[HR] =
      1.61; IC 95% 1.09-2.39; p = 0.017). RDW> = 15.3 had greater adjusted death risk
      than T1 (HR = 2.18; 95% CI 0.99-4.8; p = 0.05) and T1+T2 (HR = 1.54; 95% CI 1.13
      2.09; p = 0.006). CONCLUSION: RDW determined in optimally medicated outpatients
      with HFrEF, during dry-state, is a strong, cheap, and independent predictor of
      long-term survival.

PMID- 27716653
TI  - Erythrocyte nitric oxide availability and oxidative stress following exercise.
AB  - Growing evidence has shown that acute exercise impairs erythrocyte membrane
      structure and function as a consequence of increased physical and chemical
      stress. Erythrocyte-synthesized nitric oxide (NO) is known to modulate membrane
      fluidity, and its bioavailability depends on the balance between its production
      and scavenging by reactive oxygen species. Here, we investigated whether a
      maximal exercise test could affect erythrocyte NO bioavailability and oxidative
      stress. Twelve men (26+/-4 years old, VO2peak 44.1+/-4.3 mL.kg-1.min-1) performed
      a treadmill maximal cardiopulmonary exercise test. Blood was collected at rest
      and immediately after exercise for erythrocytes isolation. Maximal exercise
      caused an increase in erythrocytes count, haemoglobin and haematocrit levels.
      There was no change in L-arginine influx into erythrocytes after exercise. Yet,
      nitric oxide synthase activity, and thus, NO production, was increased after
      maximal test, as well cyclic GMP levels. In relation to biomarkers of oxidative
      stress, maximal test resulted in increased levels of lipid peroxidation, and
      diminished superoxide dismutase activity. Neither glutathione peroxidase nor
      catalase activity was affected by maximal test. Our findings demonstrate that the
      increased erythrocyte membrane rigidity caused by an acute bout of exercise may
      be caused, in part, by an increased lipid oxidative damage caused by ROS produced
      exogenously.

PMID- 27716654
TI  - Body fat and blood rheology: Evaluation of the association between different
      adiposity indices and blood viscosity.
AB  - BACKGROUND: In recent years, new measures of body adiposity have been introduced:
      lipid accumulation product (LAP), body adiposity index (BAI) and body shape index
      (ABSI). These indices have been demonstrated to better associate with
      cardiovascular disease than other measures of adiposity. OBJECTIVES: The aim of
      the present study was to evaluate if LAP or BAI better associate with blood
      viscosity than other measures of adiposity (body mass index, BMI; waist
      circumference, WC; waist-to-hip ratio, W/HR; waist-to-height ratio, W/HtR).
      METHODS: 344 subjects were recruited for the present investigation. Exclusion
      criteria were: diabetes, elevated triglycerides, smoking and drug use. Blood
      lipids and glucose were measured by routine methods. Blood and plasma viscosity
      were measured by a cone-plate viscometer. Adiposity measures were computed as
      previously described. RESULTS: In simple correlation analyses, blood viscosity
      (BV) correlated with BMI, BAI, and LAP in males and with LAP in females.
      Correlations between plasma viscosity and adiposity indices were weak and not
      statistically significant. Other variables significantly related with BV were:
      gender, HDL- and LDL-Cholesterol, and triglycerides (p < 0.05). In multiple
      regression analysis only LAP was associated with BV. CONCLUSIONS: Our data
      suggest that LAP index is strongly associated to blood viscosity. This result,
      along with previous evidence, identifies LAP index as a potential cardiovascular
      risk marker.

PMID- 27716655
TI  - Circulating serum CK level vs. muscle impairment for in situ monitoring burden of
      disease in Mdx-mice.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) consists of a lack in the
      expression of the subsarcolemmal protein dystrophin causing progressive muscle
      dysfunction. Among the widely applied animal models in DMD research is the
      C57BL/1010ScSn-Dmdmdx mouse, commonly referred to as the "mdx mouse". The
      potential benefit of novel interventions in this model is often assessed by
      variables such as functional improvement, histological changes, and creatine
      kinase (CK) serum levels as an indicator for the extent of in situ muscle damage.
      OBJECTIVE: Our objective was to determine to what extent the serum CK-level
      serves a surrogate for muscle dysfunction. METHODS: In this trial mdx mice were
      subjected to a four-limb wire-hanging test (WHT) to assess the physical
      performance as a reference for muscle function. As CK is a component of the
      muscle fiber cytosol, its serum activity is supposed to positively correlate with
      progressing muscle damage. Hence serum CK levels were measured to detect the
      degree of muscle impairment. The functional tests and the serum CK levels were
      analyzed for their specific correlation. RESULTS: Although physical performance
      decreased during the course of the experiment, latency to fall times in the WHT
      did not correlate with the CK level in mdx mice. CONCLUSION: Our data suggests
      that the serum CK activity might be a critical parameter to monitor the
      progression of muscle impairment in mdx mice. Further this study emphasizes the
      complexity of the DMD phenotype in the mdx mouse, and the care with which
      isolated parameters in this model should be interpreted.

PMID- 27716656
TI  - Diagnosis of perinephric retroperitoneal lymphangioma supported by contrast
      enhanced ultrasound (CEUS).
AB  - Lymphangiomas are a rare condition, which are characterized by multiple cystic
      lesions of a single or multiple organs that are thought to originate from
      intrauterine atypically distended and connected lymphatic tissue. We describe a
      case of a 56 years old woman with the final diagnosis of a perinephric
      lymphangioma. With the use of contrast-enhanced ultrasound (CEUS) it was possible
      to add valuable diagnostic information regarding the extent of the lymphangioma
      to surrounding tissue without the necessity to use additional ionizing radiation
      or nephrotoxic contrast agents.

PMID- 27716659
TI  - Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to
      Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms.
AB  - The clinical response to donepezil in patients with mild and moderate dementia
      was investigated in relation to the drug plasma concentration and APOE and CYP2D6
      polymorphisms. In a prospective naturalistic observational study, 42 patients
      with Alzheimer's disease (AD) and AD with cerebrovascular disease who took
      donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the
      donepezil plasma concentrations were measured after 3, 6, and 12 months. Good
      responders scored >=-1 on the Mini-Mental State Examination at 12 months in
      comparison to the baseline score. The study results indicated the good response
      pattern was influenced by the concentration of donepezil, but not by APOE and
      CYP2D6 polymorphisms.

PMID- 27716658
TI  - The Diagnostic and Prognostic Value of Neuropsychological Assessment in Memory
      Clinic Patients.
AB  - BACKGROUND: Neuropsychological testing has long been embedded in daily clinical
      practice at memory clinics but the added value of a complete neuropsychological
      assessment (NPA) to standard clinical evaluation is unknown. OBJECTIVE: To
      evaluate the added diagnostic and prognostic value of NPA to clinical evaluation
      only in memory clinic patients. METHODS: In 221 memory clinic patients of a
      prospective cohort study, clinical experts diagnosed clinical syndrome
      (subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or
      dementia) and etiology (Alzheimer's disease (AD) or no AD), and provided a
      prognosis of disease course (decline or no decline) before and after results of
      NPA were made available. The reference standard was a panel consensus based on
      all clinical information at baseline and up to 2 follow-up assessments. RESULTS:
      With NPA data available, clinicians changed their initial syndromal diagnosis in
      22% of patients, and the etiological diagnosis as well as the prognosis in 15%.
      This led to an increase in correctly classified cases of 18% for syndromal
      diagnosis, 5% for etiological diagnosis, and 1% for prognosis. NPA data resulted
      in the largest improvement in patients initially classified as SCI (syndrome:
      93.3% (n = 14) correctly reclassified, etiology: net reclassification improvement
      [NRI] = 0.61, prognosis: NRI = 0.13) or MCI (syndrome: 89.3% (n = 23) correctly
      reclassified, etiology: NRI = 0.17, prognosis: NRI = 0.14), while there was no
      improvement in patients with dementia (syndrome: 100% (n = 1) correctly
      reclassified, etiology: NRI = -0.05, prognosis: NRI = -0.06). Overall, inclusion
      of NPA in the diagnostic process increased confidence in all diagnoses with 6-7%.
      CONCLUSION: Administration of a complete NPA after standard clinical evaluation
      has added value for diagnosing cognitive syndrome and its underlying etiology in
      patients regarded as non-demented based on the first clinical impression.

PMID- 27716660
TI  - The Effect of Escitalopram on Mood and Cognition in Depressive Alzheimer's
      Disease Subjects.
AB  - BACKGROUND: Effective treatments to alleviate depression in Alzheimer's disease
      (AD) have been scarce. OBJECTIVE: To investigate the efficacy and tolerability of
      escitalopram in the treatment of depression in AD. METHODS: In this 12-week
      randomized, double-blind, placebo-controlled trial with open-label, 12-week
      extension, AD subjects over 50 years of age, with depression defined by Olin's
      provisional diagnostic criteria, were enrolled. The Cornell Scale for Depression
      in Dementia (CSDD), and other measures of depression and cognition were repeated.
      RESULTS: 91 subjects were screened, and 84 were randomized into either the study
      group or placebo group (n = 42 for both groups). Twenty-four subjects (29%) were
      unable to finish the study, yielding a per protocol population of 60 subjects
      (study group: n = 27; placebo group: n = 33). At week 12, differences in measures
      of depression and cognition between the two groups were not statistically
      significant. However, exploratory analysis suggested that further research on a
      subset of subjects with 'definite major depression' (baseline CSDD score >=18) is
      needed. The number of treatment-related adverse-events (AE) did not differ
      between groups (p = 0.83) and no serious treatment-related AE were observed.
      CONCLUSION: The use of escitalopram was well tolerated in depressive dementia
      patients. Future studies focusing on subjects with more severe levels of
      depression, and with more statistical power, will be needed.

PMID- 27716661
TI  - Genetic Prion Disease Caused by PRNP Q160X Mutation Presenting with an
      Orbitofrontal Syndrome, Cyclic Diarrhea, and Peripheral Neuropathy.
AB  - Patients with pathogenic truncating mutations in the prion gene (PRNP) usually
      present with prolonged disease courses with severe neurofibrillary tangle and
      cerebral amyloidosis pathology, but more atypical phenotypes also occur,
      including those with dysautonomia and peripheral neuropathy. We describe the
      neurological, cognitive, neuroimaging, and electrophysiological features of a 31
      year-old man presenting with an orbitofrontal syndrome, gastrointestinal
      symptoms, and peripheral neuropathy associated with PRNP Q160X nonsense mutation,
      with symptom onset at age 27. The mutation was also detected in his asymptomatic
      father and a symptomatic paternal cousin; several members of prior generations
      died from early onset dementia. This is the first report of a family affected
      with the nonsense PRNP mutation Q160X displaying clear autosomal dominant disease
      in multiple family members and reduced penetrance. This case strengthens the
      evidence suggesting an association between PRNP truncating mutations and prion
      systemic amyloidosis. PRNP gene testing should be considered in any patient with
      atypical dementia, especially with early onset and neuropathy, even in the
      absence of a family history.

PMID- 27716663
TI  - Cerebrospinal Fluid Biomarkers for the Differential Diagnosis between Alzheimer's
      Disease and Frontotemporal Lobar Degeneration: Systematic Review, HSROC Analysis,
      and Confounding Factors.
AB  - BACKGROUND: Differential diagnosis in dementia is at present one of the main
      challenges both in clinical practice and research. Cerebrospinal fluid (CSF)
      biomarkers are included in the current diagnostic criteria of Alzheimer's disease
      (AD) but their clinical utility is still unclear. OBJECTIVE: We performed a
      systematic review of studies analyzing the diagnostic performance of CSF Abeta42,
      total tau (t-tau), and phosphorylated tau (p-tau) in the discrimination between
      AD and frontotemporal lobar degeneration (FTLD) dementias. METHODS: The following
      electronic databases were consulted until May 2016: Medline and PreMedline,
      EMBASE, PsycInfo, CINAHL, Cochrane Library, and CRD. For the first-time in the
      field, a Hierarchical Summary Receiver Operating Characteristic (HRSOC) model was
      applied, which avoids methodological problems of meta-analyses based on summary
      points of sensitivity and specificity values. We also investigated relevant
      confounders of CSF biomarkers' diagnostic performance such as age, disease
      duration, and global cognitive impairment. RESULTS: The p-tau/Abeta42 ratio
      showed the best diagnostic performance. No statistically significant effects of
      the confounders were observed. Nonetheless, the p-tau/Abeta42 ratio may be
      especially indicated for younger patients. P-tau may be preferable for less
      cognitively impaired patients (high MMSE scores) and the t-tau/Abeta42 ratio for
      more cognitively impaired patients (low MMSE scores). CONCLUSION: The p
      tau/Abeta42 ratio has potential for being implemented in the clinical routine for
      the differential diagnosis between AD and FTLD. It is of utmost importance that
      future studies report information on confounders such as age, disease duration,
      and cognitive impairment, which should also stimulate understanding of the role
      of these factors in disease mechanisms and pathophysiology.

PMID- 27716664
TI  - Normal Vitamin Levels and Nutritional Indices in Alzheimer's Disease Patients
      with Mild Cognitive Impairment or Dementia with Normal Body Mass Indexes.
AB  - Evidence supports an association between vitamin deficiencies and cognitive
      decline in Alzheimer's disease (AD). If vitamin deficiencies are causative for AD
      development, they should be detectable during very early stages of AD. Here we
      investigated nutritional factors among home-living patients diagnosed with mild
      cognitive impairment (MCI) or mild dementia due to AD, compared to healthy
      controls. Our study included 73 patients with AD (25 with MCI, 48 with dementia)
      and 63 cognitively intact age-matched controls. All participants underwent
      cognitive testing, somatic examination, and measurements of vitamins A, B1, B6,
      folate, B12, C, D, and E, and F2-alpha-isoprostane. Results are given as mean
      (SD). MMSE scores were 29.1 (1.0) for healthy controls, 27.4 (1.8) for patients
      with MCI, and 24.3 (3.2) for patients with dementia. Vitamin concentrations for
      the these groups, respectively, were as follows: B1 (nmol/l), 157 (29), 161 (35),
      and 161 (32); B6 (nmol/l), 57 (63), 71 (104), and 58 (44); folate (mmol/l), 23
      (9), 26 (10), and 23 (11); B12 (pmol/l), 407 (159), 427 (116), and 397 (204); C
      (MUmol/l), 63 (18), 61 (16), and 63 (29); A (MUmol/l), 2.3 (0.6), 2.2 (0.5), and
      2.3 (0.5); E (MUmol/l), 36 (6.3), 36 (6.9), and 36 (8.2); 25-OH vitamin D
      (nmol/l), 65 (18), 61 (19), and 65 (20); and 8-iso-PGFalpha (pg/ml), 64 (27); 60
      (19), and 66 (51). These concentrations did not significantly differ (p<=0.05)
      between the three groups. Our results do not support the hypothesis that vitamin
      deficiencies play a causative role in the development of early cognitive
      impairment.

PMID- 27716665
TI  - Effects of DHA Supplementation on Hippocampal Volume and Cognitive Function in
      Older Adults with Mild Cognitive Impairment: A 12-Month Randomized, Double-Blind,
      Placebo-Controlled Trial.
AB  - Docosahexaenoic acid (DHA) is important for brain function, and higher DHA intake
      is inversely correlated with relative risk of Alzheimer's disease. The potential
      benefits of DHA supplementation in people with mild cognitive impairment (MCI)
      have not been fully examined. Our study aimed to determine the effect of DHA
      supplementation on cognitive function and hippocampal atrophy in elderly subjects
      with MCI. This was a randomized, double-blind, placebo-controlled trial in
      Tianjin, China. 240 individuals with MCI aged 65 years and over were recruited
      and equalized randomly allocated to the DHA or the placebo group. Participants
      received 12-month DHA supplementation (2 g/day) or corn oil as placebo. Both
      global and specific subdomains of cognitive function and hippocampal volume were
      measured at baseline, 6 months, and 12 months. Both changes were analyzed by
      repeated-measure analysis of variance (ANOVA). This trial has been registered:
      ChiCTR-IOR-15006058. A total of 219 participants (DHA: 110, Placebo: 109)
      completed the trial. The change in mean serum DHA levels was greater in the
      intervention group (+3.85%) compared to the control group (+1.06%). Repeated
      measures analyses of covariance showed that, over 12 months, there was a
      significant difference in the Full-Scale Intelligence Quotient (etap2 = 0.084; p
      = 0.039), Information (etap2 = 0.439; p = 0.000), and Digit Span (etap2 = 0.375;
      p = 0.000) between DHA-treated versus the placebo group. In addition, there were
      significant differences in volumes of left hippocampus (etap2 = 0.121, p =
      0.016), right hippocampus (etap2 = 0.757, p = 0.008), total hippocampus (etap2 =
      0.124, p = 0.023), and global cerebrum (etap2 = 0.145, p = 0.032) between the two
      groups. These findings suggest that DHA supplementation (2 g/day) for 12 months
      in MCI subjects can significantly improve cognitive function and slow the
      progression of hippocampal atrophy. Larger, longer-term confirmatory studies are
      warranted.

PMID- 27716662
TI  - Neutrophil Gelatinase-Associated Lipocalin and its Receptors in Alzheimer's
      Disease (AD) Brain Regions: Differential Findings in AD with and without
      Depression.
AB  - Co-existing depression worsens Alzheimer's disease (AD) pathology. Neutrophil
      gelatinase-associated lipocalin (NGAL) is a newly identified (neuro)inflammatory
      mediator in the pathophysiologies of both AD and depression. This study aimed to
      compare NGAL levels in healthy controls, AD without depression (AD-D), and AD
      with co-existing depression (AD+D) patients. Protein levels of NGAL and its
      receptors, 24p3R and megalin, were assessed in nine brain regions from healthy
      controls (n = 19), AD-D (n = 19), and AD+D (n = 21) patients. NGAL levels in AD-D
      patients were significantly increased in brain regions commonly associated with
      AD. In the hippocampus, NGAL levels were even further increased in AD+D subjects.
      Unexpectedly, NGAL levels in the prefrontal cortex of AD+D patients were
      comparable to those in controls. Megalin levels were increased in BA11 and
      amygdala of AD+D patients, while no changes in 24p3R were detected. These
      findings indicate significant differences in neuroimmunological regulation
      between AD patients with and without co-existing depression. Considering its
      known effects, elevated NGAL levels might actively promote neuropathological
      processes in AD with and without depression.

PMID- 27716666
TI  - Recent Increases in Hippocampal Tau Pathology in the Aging Japanese Population:
      The Hisayama Study.
AB  - BACKGROUND: The Hisayama study is a prospective cohort study of lifestyle-related
      diseases that commenced in 1961. Through it, a significant increasing trend in
      the prevalence of Alzheimer's disease has been observed over the past 18 years.
      OBJECTIVES: We sought to investigate the increases in brain pathology related to
      Alzheimer's disease using automated MATLAB morphometric analyses for quantifying
      tau pathology. METHODS: We examined a series of autopsied cases from Hisayama
      residents obtained between 1998 and 2003 (group A: 203 cases), and between 2009
      and 2014 (group B: 232 cases). We developed custom software in MATLAB to analyze
      abnormal tau deposits quantitatively. Specimens were immunostained with both anti
      amyloid-beta-protein and anti-phosphorylated tau antibodies. RESULTS: Both the
      Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for
      senile plaques and Braak stage for NFT were higher in group B. Morphometric
      analyses of the hippocampi also revealed a trend toward increased tau pathology
      in both men and women over 80 years of age in group B. The increases were also
      significant when the subjects were examined independently according to high or
      low CERAD scores and in all levels of AD neuropathologic change according to the
      National Institute on Aging-Alzheimer's Association guidelines (2012).
      CONCLUSION: We revealed a recent trend of increased tauopathy in the older
      people, which is partly independent of amyloid-beta pathology.

PMID- 27716667
TI  - Modeling the Distress of Spousal Caregivers of People with Dementia.
AB  - BACKGROUND: The progressive mobilization of spouse caregivers who take care of a
      person with dementia (PWD) can lead to situations of distress. OBJECTIVE: The
      current study sought to investigate the influence of the characteristics of the
      caregiving context on spousal caregiver distress. METHODS: 125 spousal caregivers
      participated in this study. The characteristics of the caregiving context were
      assessed using questionnaires. We examined a moderated-mediator model (Step 1) in
      which we hypothesized that PWD and caregiver characteristics and dyadic
      determinants contribute to spousal caregiver distress. This model was compared
      based on the age at onset of the disease and the gender of the caregiver (Step
      2). RESULTS: The model revealed that poor self-rated health and a lack of family
      support accentuated spousal caregiver distress, whereas the feeling of being
      prepared and level of confidence decreased spousal caregiver distress. Moreover,
      the quality of couple adjustment affected spousal caregiver distress, and this
      effect was mediated by the severity of the PWD's symptoms. Regarding the age at
      onset of the disease, the path between Couple Adjustment and the Care recipient's
      impairments was more important for caregivers of person with early-onset dementia
      (PEOD). Female caregivers who reported poor self-rated health experienced greater
      distress. CONCLUSIONS: It would be interesting to create a support program that
      would incorporate these three areas of intervention regarding the progression of
      the disease: first, "preparedness modules"; second, "dyadic modules" (especially
      for caregivers of PEOD); and third, "family modules". Specific attention should
      be given to female caregivers who report poor self-rated health.

PMID- 27716668
TI  - Potentially Inappropriate Medication in Community-Dwelling Primary Care Patients
      who were Screened Positive for Dementia.
AB  - BACKGROUND: Potentially inappropriate medication (PIM) in older people is a risk
      factor for adverse drug effects. This risk is even higher in older people with
      dementia (PWD). OBJECTIVE: Our study aimed to determine (1) the prevalence of PIM
      among primary care patients who were screened positive for dementia and (2) the
      sociodemographic and clinical variables associated with the use of PIM. METHODS:
      DelpHi-MV (Dementia: life- and person-centered help in Mecklenburg-Western
      Pomerania) is a general practitioner-based, cluster-randomized, controlled
      intervention study to implement and evaluate an innovative concept of
      collaborative dementia care management in Germany. The comprehensive baseline
      assessment includes a home medication review. The present analyses are based on
      the data from 448 study participants (age 70+, DemTect <9). PIMs were identified
      using the list of Potentially Inappropriate Medications in the Elderly (Priscus).
      RESULTS: (1) A total of 99 study participants (22%) received at least one PIM.
      The highest prevalence was found for antidepressants, benzodiazepines, and
      analgetics. The most frequently prescribed PIMs were amitriptyline, etoricoxib,
      and doxazosin. (2) Use of a PIM was significantly associated with a diagnosis of
      a mental or behavioral disorder. CONCLUSIONS: The prescription rate of PIMs for
      community-dwelling PWD was comparable with the rates found for the general
      population of older people in Germany (20-29%). Antidepressants with
      anticholinergic properties and long-acting benzodiazepines were the most
      prescribed PIMs, despite having an unfavorable benefit-risk ratio. This high
      prevalence of PIM prescriptions in a vulnerable population of PWD indicates that
      standard care for dementia should include careful medication review and
      management.

PMID- 27716669
TI  - Daily Physical Activity Patterns During the Early Stage of Alzheimer's Disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that results
      in severe disability. Very few studies have explored changes in daily physical
      activity patterns during early stages of AD when components of physical function
      and mobility may be preserved. OBJECTIVE: Our study explored differences in daily
      physical activity profiles, independent of the effects of non-cognitive factors
      including physical function and age, among individuals with mild AD compared to
      controls. METHODS: Patients with mild AD and controls (n = 92) recruited from the
      University of Kansas Alzheimer's Disease Center Registry, wore the Actigraph
      GT3X+ for seven days, and provided objective physical function (VO2 max) and
      mobility data. Using multivariate linear regression, we explored whether
      individuals with mild AD had different daily average and diurnal physical
      activity patterns compared to controls independent of non-cognitive factors that
      may affect physical activity, including physical function and mobility. RESULTS:
      We found that mild AD was associated with less moderate-intensity physical
      activity (p < 0.05), lower peak activity (p < 0.01), and lower physical activity
      complexity (p < 0.05) particularly during the morning. Mild AD was not associated
      with greater sedentary activity or less lower-intensity physical activity across
      the day after adjusting for non-cognitive covariates. CONCLUSIONS: These findings
      suggest that factors independent of physical capacity and mobility may drive
      declines in moderate-intensity physical activity, and not lower-intensity or
      sedentary activity, during the early stage of AD. This underscores the importance
      of a better mechanistic understanding of how cognitive decline and AD pathology
      impact physical activity. Findings emphasize the potential value of designing and
      testing time-of-day specific physical activity interventions targeting
      individuals in the early stages of AD, prior to significant declines in mobility
      and physical function.

PMID- 27716670
TI  - BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise,
      Cognitive Training, and Mindfulness: Associations with Working Memory Function.
AB  - Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity
      by mediating changes in cortical thickness and synaptic density in response to
      physical activity and environmental enrichment. Previous studies suggest that
      physical exercise can augment BDNF levels, both in serum and the brain, but no
      other study has examined how different types of activities compare with physical
      exercise in their ability to affect BDNF levels. By using a balanced cross over
      experimental design, we exposed nineteen healthy older adults to 35-minute
      sessions of physical exercise, cognitive training, and mindfulness practice, and
      compared the resulting changes in mature BDNF levels between the three
      activities. We show that a single bout of physical exercise has significantly
      larger impact on serum BDNF levels than either cognitive training or mindfulness
      practice in the same persons. This is the first study on immediate BDNF effects
      of physical activity in older healthy humans and also the first study to
      demonstrate an association between serum BDNF responsivity to acute physical
      exercise and working memory function. We conclude that the BDNF increase we found
      after physical exercise more probably has a peripheral than a central origin, but
      that the association between post-intervention BDNF levels and cognitive function
      could have implications for BDNF responsivity in serum as a potential marker of
      cognitive health.

PMID- 27716671
TI  - Effects of Tooth Loss and the Apolipoprotein E E4 Allele on Mild Memory
      Impairment in the Fujiwara-kyo Study of Japan: A Nested Case-Control Study.
AB  - BACKGROUND: Several studies have suggested that periodontal disease can
      exacerbate the pro-inflammatory status of the brain. Tooth loss is one of the
      alternative evaluation indices of periodontal disease. There are few data on the
      relationship between tooth loss and memory impairment, depending on the
      apolipoprotein E (APOE) E4 genotype. OBJECTIVE: To determine if tooth loss is
      associated with mild memory impairment (MMI) and if this association is modified
      by the presence of the APOEE4 allele. METHODS: A nested case-control study was
      conducted from 2007 to 2012 in Japan. Five hundred and thirty-seven Japanese
      subjects aged 65 years and over who were cognitively intact at baseline were
      analyzed. MMI at follow-up was evaluated. RESULTS: The median number of teeth at
      baseline was significantly lower in MMI participants (n = 179) than in controls
      (n = 358) (MMI: median 21.0, interquartile range 10.0-25.0 versus controls: 24.0,
      14.0-27.0). After adjustment for demographics, vascular risk factors, and APOEE4
      allele, the multivariate adjusted odds ratio (OR) of <=8 teeth was 1.97 (95%
      confidence interval [CI], 1.13-3.44) compared to 25-32 teeth. Participants with
      both the presence of at least 1 APOEE4 allele and <=8 teeth had a higher risk of
      MMI compared with those with neither (OR, 2.82; 95% CI, 1.15-6.91). Those with
      either risk factor alone did not have a higher risk of MMI. CONCLUSIONS: A lower
      number of teeth is related to risk of MMI. This may be primarily true for those
      individuals with an APOEE4 allele.

PMID- 27716673
TI  - The Utilization of Robotic Pets in Dementia Care.
AB  - BACKGROUND: Behavioral problems may affect individuals with dementia, increasing
      the cost and burden of care. Pet therapy has been known to be emotionally
      beneficial for many years. Robotic pets have been shown to have similar positive
      effects without the negative aspects of traditional pets. Robotic pet therapy
      offers an alternative to traditional pet therapy. OBJECTIVE: The study rigorously
      assesses the effectiveness of the PARO robotic pet, an FDA approved biofeedback
      device, in treating dementia-related symptoms. METHODS: A randomized block design
      with repeated measurements guided the study. Before and after measures included
      reliable, valid tools such as: RAID, CSDD, GDS, pulse rate, pulse oximetry, and
      GSR. Participants interacted with the PARO robotic pet, and the control group
      received standard activity programs. Five urban secure dementia units comprised
      the setting. RESULTS: 61 patients, with 77% females, average 83.4 years in age,
      were randomized into control and treatment groups. Compared to the control group,
      RAID, CSDD, GSR, and pulse oximetry were increased in the treatment group, while
      pulse rate, pain medication, and psychoactive medication use were decreased. The
      changes in GSR, pulse oximetry, and pulse rate over time were plotted for both
      groups. The difference between groups was consistent throughout the 12-week study
      for pulse oximetry and pulse rate, while GSR had several weeks when changes were
      similar between groups. CONCLUSIONS: Treatment with the PARO robot decreased
      stress and anxiety in the treatment group and resulted in reductions in the use
      of psychoactive medications and pain medications in elderly clients with
      dementia.

PMID- 27716672
TI  - Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive
      Function in AbetaPP/PS1 Mice.
AB  - Alzheimer's disease (AD) is the most common cause of dementia. The cardinal
      neuropathological characteristic of AD is the accumulation of amyloid-beta
      (Abeta) into extracellular plaques that ultimately disrupt neuronal function and
      lead to neurodegeneration. One possible therapeutic strategy therefore is to
      prevent Abeta aggregation. Previous studies have suggested that vitamin E analogs
      slow AD progression in humans. In the present study, we investigated the effects
      of the tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs from palm
      oil, on amyloid pathology in vitro and in vivo. TRF treatment dose-dependently
      inhibited the formation of Abeta fibrils and Abeta oligomers in vitro. Moreover,
      daily TRF supplementation to AbetaPPswe/PS1dE9 double transgenic mice for 10
      months attenuated Abeta immunoreactive depositions and thioflavin-S-positive
      fibrillar type plaques in the brain, and eventually improved cognitive function
      in the novel object recognition test compared with control AbetaPPswe/PS1dE9
      mice. The present result indicates that TRF reduced amyloid pathology and
      improved cognitive functions, and suggests that TRF is a potential therapeutic
      agent for AD.

PMID- 27716674
TI  - Insula and Inferior Frontal Gyrus' Activities Protect Memory Performance Against
      Alzheimer's Disease Pathology in Old Age.
AB  - Apolipoprotein E (APOE) E4 carriers and patients with amnestic mild cognitive
      impairment (MCI) have high risk of developing Alzheimer's disease (AD). The
      Scaffolding Theory of Aging and Cognition proposes that recruitment of additional
      frontal brain regions can protect cognition against aging. This thesis has yet to
      be fully tested in older adults at high risk for AD. In the present study, 75
      older participants (mean age: 74 years) were included. Applying a voxel-wise
      approach, fractional amplitude of low-frequency fluctuations (fALFF) in resting
      state functional neuroimaging data were analyzed as a function of APOEE4 status
      (carrier versus noncarrier) and clinical status (healthy control [HC] versus MCI)
      using a 2*2 analysis of covariance (ANCOVA). Measures of cognition and
      cerebrospinal fluid levels of amyloid- beta were also obtained. Three frontal
      regions were identified with significant interaction effects using ANCOVA
      (corrected p < 0.01): left-insula, left-inferior frontal gyrus (IFG), and right
      precentral gyrus. The HC/APOEE4 carrier group had significantly higher fALFF in
      all three regions than other groups. In the entire sample, for two regions (left
      insula and left IFG), a significant positive relationship between amyloid-beta
      and memory was only observed among individuals with low fALFF. Our results
      suggest higher activity in frontal regions may explain being cognitively normal
      among a subgroup of APOEE4 carriers and protect against the negative impact of AD
      associated pathology on memory. This is an observation with potential
      implications for AD therapeutics.

PMID- 27716676
TI  - Inflammation, Antiinflammatory Agents, and Alzheimer's Disease: The Last 22
      Years.
AB  - Two basic discoveries spurred research into inflammation as a driving force in
      the pathogenesis of Alzheimer's disease (AD). The first was the identification of
      activated microglia in association with the lesions. The second was the discovery
      that rheumatoid arthritics, who regularly consume anti-inflammatory agents, were
      relatively spared from the disease. These findings led to an exploration of the
      inflammatory pathways that were involved in AD pathogenesis. A pivotal advance
      was the discovery that amyloid-beta protein (Abeta) activated the complement
      system. This focused attention on anti-inflammatories as blockers of complement
      activation. More than 15 epidemiological studies have since showed a sparing
      effect of non-steroidal anti-inflammatory drugs (NSAIDs) in AD. A consistent
      finding has been that the longer the NSAIDs were used prior to clinical
      diagnosis, the greater the sparing effect. The reason has since emerged from
      studies of biomarkers such as amyloid-beta (Abeta) levels in the cerebrospinal
      fluid and Abeta deposits in brain. They have established that the onset of AD
      commences at least a decade before cognitive decline permits clinical diagnosis.
      Such biomarker studies have revealed that a huge window of opportunity exists
      when application of NSAIDs, other anti-inflammatory agents, or complement
      activation blockers, could arrest further progress of AD, thus eliminating its
      manifestation. It can be anticipated that this principle will apply to many other
      chronic neurodegenerative diseases. Neuroinflammation, discovered in AD more than
      30 years ago, has now become a major field of brain research today. Inhibiting it
      may be the key to successful treatment of many chronic neurological disorders.

PMID- 27716675
TI  - Tau Oligomers Associate with Inflammation in the Brain and Retina of Tauopathy
      Mice and in Neurodegenerative Diseases.
AB  - It is well-established that inflammation plays an important role in Alzheimer's
      disease (AD) and frontotemporal lobar dementia (FTLD). Inflammation and synapse
      loss occur in disease prior to the formation of larger aggregates, but the
      contribution of tau to inflammation has not yet been thoroughly investigated. Tau
      pathologically aggregates to form large fibrillar structures known as tangles.
      However, evidence suggests that smaller soluble aggregates, called oligomers, are
      the most toxic species and form prior to tangles. Furthermore, tau oligomers can
      spread to neighboring cells and between anatomically connected brain regions. In
      addition, recent evidence suggests that inspecting the retina may be a window to
      brain pathology. We hypothesized that there is a relationship between tau
      oligomers and inflammation, which are hallmarks of early disease. We conducted
      immunofluorescence and biochemical analyses on tauopathy mice, FTLD, and AD
      subjects. We showed that oligomers co-localize with astrocytes, microglia, and
      HMGB1, a pro-inflammatory cytokine. Additionally, we show that tau oligomers are
      present in the retina and are associated with inflammatory cells suggesting that
      the retina may be a valid non-invasive biomarker for brain pathology. These
      results suggest that there may be a toxic relationship between tau oligomers and
      inflammation. Therefore, the ability of tau oligomers to spread may initiate a
      feed-forward cycle in which tau oligomers induce inflammation, leading to
      neuronal damage, and thus more inflammation. Further mechanistic studies are
      warranted in order to understand this relationship, which may have critical
      implications for improving the treatment of tauopathies.

PMID- 27716678
TI  - The Presence of Select Tau Species in Human Peripheral Tissues and Their Relation
      to Alzheimer's Disease.

PMID- 27716679
TI  - A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic
      Resonance Imaging.

PMID- 27716680
TI  - Comparison of Huntington's disease CAG Repeat Length Stability in Human Motor
      Cortex and Cingulate Gyrus.
AB  - Huntington's disease is caused by expansion of the CAG repeat in Huntingtin. This
      repeat has shown tissue-specific instability in mouse models and in a small
      number of post-mortem human samples. We used small-pool PCR to generate a
      modified instability index to quantify CAG instability within two brain regions
      from six human samples where cell loss has been associated with motor and mood
      symptoms: the motor cortex and cingulate gyrus. The expanded allele demonstrated
      instability in both regions, with minimal instability in the unexpanded allele.
      Region-specific differences were not observed, suggesting symptomatology may not
      be determined by repeat length instability.

PMID- 27716681
TI  - Separable scatter model of the detector and object contributions using
      continuously thickness-adapted kernels in CBCT.
AB  - Due to the increased cone beam coverage and the introduction of flat panel
      detector, the size of X-ray illumination fields has grown dramatically in Cone
      Beam Computed Tomography (CBCT), causing an increase in scatter radiation.
      Existing reconstruction algorithms do not model the scatter radiation, so scatter
      artifacts appear in the reconstruction images. The contribution of scattering of
      photons inside the detector itself becomes prominent and challenging in case of X
      ray source of high energy (over a few 100 keV) which is used in typical
      industrial Non Destructive Testing (NDT). In this paper, comprehensive evaluation
      of contribution of detector scatter is performed using continuously thickness
      adapted kernels. A separation of scatter due to object and the detector is
      presented using a four-Gaussian model. The results obtained prove that the
      scatter correction only due to the object is not sufficient to obtain
      reconstruction image free from artifacts as the detector also scatters
      considerably. The obtained results are also validated experimentally using a
      collimator to remove the contribution of object scatter.

PMID- 27716682
TI  - From the Editor's desk.

PMID- 27716683
TI  - Perioperative transesophageal echocardiography: State of the art 2016.

PMID- 27716684
TI  - Recent trends on hemodynamic monitoring in cardiac surgery.

PMID- 27716685
TI  - Platelet aggregometry interpretation using ROTEM - PART - II.

PMID- 27716686
TI  - Transesophageal echocardiography in an atrioventricular septal defect.

PMID- 27716687
TI  - Different transseptal puncture for different procedures: Optimization of left
      atrial catheterization guided by transesophageal echocardiography.
AB  - BACKGROUND: Left atrial catheterization through transseptal puncture is
      frequently performed in cardiac catheterization procedures. Appropriate
      transseptal puncture is critical to achieve procedural success. AIMS: The aim of
      the study is to evaluate the feasibility of selective transseptal punctures,
      using a modified radiofrequency (RF) transseptal needle and transesophageal
      echocardiography (TEE), in different types of procedures that require specific
      sites of left atrial catheterization. SETTING AND DESIGN: This was an
      observational trial in a cardiac catheterization laboratory of a teaching
      hospital. MATERIALS AND METHODS: Patients undergoing different percutaneous
      procedures requiring atrial transseptal puncture such as atrial fibrillation (AF)
      ablation, left atrial appendage (LAA) occlusion, and mitral valve repair were
      included in the study. All procedures were guided by TEE and an RF transseptal
      needle targeting a specific region of the septum to perform the puncture.
      STATISTICAL ANALYSIS: The statistical analysis was descriptive only. RESULTS: RF
      assisted transseptal punctures were performed in six consecutive patients who
      underwent AF ablation (two patients), LAA closure (two patients), and mitral
      valve repair (two patients). In all patients, transseptal punctures were
      performed successfully at the desired site. No adverse events or complications
      were observed. CONCLUSIONS: Selective transseptal puncture, using TEE and an RF
      needle, is a feasible technique that can be used in multiple approaches requiring
      a precise site of access for left atrial catheterization.

PMID- 27716688
TI  - Accidental arterial puncture during right internal jugular vein cannulation in
      cardiac surgical patients.
AB  - BACKGROUND: The primary aim of this study was to compare the incidence of
      accidental arterial puncture during right internal jugular vein (RIJV)
      cannulation with and without ultrasound guidance (USG). The secondary end points
      were to assess if USG improves the chances of successful first pass cannulation
      and if BMI has an impact on incidence of arterial puncture and the number of
      attempts that are to be made for successful cannulation. SETTINGS AND DESIGN:
      Prospective observational study performed at a single tertiary cardiac care
      center. MATERIAL AND METHODS: 255 consecutive adult and pediatric cardiac
      surgical patients were included. In Group I (n = 124) USG was used for the right
      internal jugular vein cannulation and in Group II (n = 81) it was not used. There
      were 135 adult patients and 70 pediatric patients. STATISTICAL ANALYSIS:
      Demographic and categorical data were analyzed using Student 't' test and chi-
      square test was used for qualitative variables. RESULTS: The overall incidence of
      accidental arterial puncture in the entire study population was significantly
      higher when ultrasound guidance was not used (P< 0.001). In subgroup analysis,
      incidence of arterial puncture was significant in both adult (P = 0.03) and
      pediatric patients (P< 0.001) without USG. First attempt cannulation was more
      often possible in pediatric patients under USG (P = 0.03). In adult patients USG
      did not improve first attempt cannulation except in underweight patients.
      CONCLUSIONS: USG helped in the avoidance of inadvertent arterial puncture during
      RIJV cannulation and simultaneously improved the chances of first attempt
      cannulation in pediatric and in underweight adult cardiac surgical patients.

PMID- 27716689
TI  - Tricuspid annulus: A spatial and temporal analysis.
AB  - BACKGROUND: Traditional two-dimensional (2D) echocardiographic evaluation of
      tricuspid annulus (TA) dilation is based on single-frame measurements of the
      septolateral (S-L) dimension. This may not represent either the axis or the
      extent of dynamism through the entire cardiac cycle. In this study, we used real
      time 3D transesophageal echocardiography (TEE) to analyze geometric changes in
      multiple axes of the TA throughout the cardiac cycle in patients without right
      ventricular abnormalities. MATERIALS AND METHODS: R-wave-gated 3D TEE images of
      the TA were acquired in 39 patients undergoing cardiovascular surgery. The
      patients with abnormal right ventricular/tricuspid structure or function were
      excluded from the study. For each patient, eight points along the TA were traced
      in the 3D dataset and used to reconstruct the TA at four stages of the cardiac
      cycle (end- and mid-systole, end- and mid-diastole). Statistical analyses were
      applied to determine whether TA area, perimeter, axes, and planarity changed
      significantly over each stage of the cardiac cycle. RESULTS: TA area (P = 0.012)
      and perimeter (P = 0.024) both changed significantly over the cardiac cycle. Of
      all the axes, only the posterolateral-anteroseptal demonstrated significant
      dynamism (P < 0.001). There was also a significant displacement in the vertical
      axis between the points and the regression plane in end-systole (P < 0.001), mid
      diastole (P = 0.014), and mid-systole (P < 0.001). CONCLUSIONS: The TA
      demonstrates selective dynamism over the cardiac cycle, and its axis of maximal
      dynamism is different from the axis (S-L) that is routinely measured with 2D TEE.

PMID- 27716690
TI  - The myocardial protective effect of dexmedetomidine in high-risk patients
      undergoing aortic vascular surgery.
AB  - OBJECTIVE: The aim of the study was to assess the effect of dexmedetomidine in
      high-risk patients undergoing aortic vascular surgery. DESIGN: A randomized
      prospective study. SETTING: Cairo University, Egypt. MATERIALS AND METHODS: The
      study included 150 patients undergoing aortic vascular surgery. INTERVENTION: The
      patients were classified into two groups (n = 75). Group D: The patients received
      a loading dose of 1 MUg/kg dexmedetomidine over 15 min before induction and
      maintained as an infusion of 0.3 MUg/kg/h to the end of the procedure. Group C:
      The patients received an equal volume of normal saline. The medication was
      prepared by the nursing staff and given to anesthetist blindly. MEASUREMENTS: The
      monitors included the heart rate, mean arterial blood pressure, central venous
      pressure, electrocardiogram (ECG), serum troponin I level, end-tidal sevoflurane,
      and total dose of morphine in addition transthoracic echocardiography to the
      postoperative in cases with elevated serum troponin I level. MAIN RESULTS: The
      dexmedetomidine decreased heart rate and minimized the changes in blood pressure
      compared to control group (P < 0.05). Furthermore, it decreased the incidence of
      myocardial ischemia reflected by troponin I level, ECG changes, and the
      development of new regional wall motion abnormalities (P < 0.05). Dexmedetomidine
      decreased the requirement for nitroglycerin and norepinephrine compared to
      control group (P < 0.05). The incidence of hypotension and bradycardia was
      significantly higher with dexmedetomidine (P < 0.05). CONCLUSION: The
      dexmedetomidine is safe and effective in patients undergoing aortic vascular
      surgery. It decreases the changes in heart rate and blood pressure during the
      procedures. It provides cardiac protection in high-risk patients reflected by
      decreasing the incidence of myocardial ischemia and serum level of troponin. The
      main side effects of dexmedetomidine were hypotension and bradycardia.

PMID- 27716691
TI  - The efficacy of pre-emptive dexmedetomidine versus amiodarone in preventing
      postoperative junctional ectopic tachycardia in pediatric cardiac surgery.
AB  - OBJECTIVE: The objective of this study was to assess the effectiveness of pre
      emptive dexmedetomidine versus amiodarone in preventing junctional ectopic
      tachycardia (JET) in pediatric cardiac surgery. DESIGN: This is a prospective,
      controlled study. SETTING: This study was carried out at a single university
      hospital. SUBJECTS AND METHODS: Ninety patients of both sexes, American Society
      of Anesthesiologists Physical Status II and III, age range from 2 to 18 years,
      and scheduled for elective cardiac surgery for congenital and acquired heart
      diseases were selected as the study participants. INTERVENTIONS: Patients were
      randomized into three groups (30 each). Group I received dexmedetomidine 1 mcg/kg
      diluted in 100 ml of normal saline intravenously (IV) over a period of 20 min,
      and the infusion was completed 10 min before the induction followed by a 0.5
      mcg/kg/h infusion for 72 h postoperative, Group II received amiodarone 5 mg/kg
      diluted in 100 ml of normal saline IV over a period of 20 min, and the infusion
      was completed 10 min before the induction followed by a 10-15 mcg/kg/h infusion
      for 72 h postoperative, and Group III received 100 ml of normal saline IV.
      Primary outcome was the incidence of postoperative JET. Secondary outcomes
      included vasoactive-inotropic score, ventilation time (VT), pediatric cardiac
      care unit stay, hospital length of stay, and perioperative mortality.
      MEASUREMENTS AND MAIN RESULTS: The incidence of JET was significantly reduced in
      Group I and Group II (P = 0.004) compared to Group III. Heart rate while coming
      off from cardiopulmonary bypass (CPB) was significantly low in Group I compared
      to Group II and Group III (P = 0.000). Mean VT, mean duration of Intensive Care
      Unit stay, and length of hospital stay (day) were significantly short (P = 0.000)
      in Group I and Group II compared to Group III (P = 0.000). CONCLUSION:
      Perioperative use of dexmedetomidine and amiodarone is associated with
      significantly decreased incidence of JET as compared to placebo without
      significant side effects.

PMID- 27716692
TI  - Comparison between marked versus unmarked introducer needle in real-time
      ultrasound-guided central vein cannulation: A prospective randomized study.
AB  - INTRODUCTION: Introducer needle tip is not clearly visible during the real-time
      ultrasound (US)-guided central vein cannulation (CVC). Blind tip leads to
      mechanical complications. This study was designed to evaluate whether real-time
      US-guided CVC with a marked introducer needle is superior to the existing
      unmarked needle. METHODOLOGY: Sixty-two critically ill patients aged 18-60 years
      of either sex were included in the study. The patients were randomized into two
      groups based on whether a marked or unmarked introducer needle was used. Both
      groups underwent real-time US-guided CVC by a single experienced operator.
      Aseptically, introducer needle was indented with markings spaced 0.5 cm (single
      marking) and every 1 cm (double marking). This needle was used in the marked
      group. Approximate depths (centimeter) of the anterior and posterior wall of the
      internal jugular vein, anterior wall of the internal carotid artery, and lung
      pleura were appreciated from the midpoint of the probe in short-axis view at the
      level of the cricoid cartilage. Access time (seconds) was recorded using a
      stopwatch. A number of attempts and complications such as arterial puncture,
      hematoma, and pneumothorax of either procedure were compared. RESULTS: Both
      marked needle and unmarked needle groups were comparable with regard to age,
      gender, severity scores, platelet counts, prothrombin time, and distance from the
      midpoint of the probe to the vein, artery, and pleura and skin-to-guide wire
      insertion access time. However, an average number of attempts (P = 0.03) and
      complications such as hematoma were significantly lower (P = 0.02) with the
      marked introducer needle group. Pneumothorax was not reported in any of the
      groups. CONCLUSION: Our study supports the idea that marked introducer needle can
      further reduce the iatrogenic complications of US-guided CVC.

PMID- 27716694
TI  - Perioperative utility of goal-directed therapy in high-risk cardiac patients
      undergoing coronary artery bypass grafting: "A clinical outcome and biomarker
      based study".
AB  - Goal-directed therapy (GDT) encompasses guidance of intravenous (IV) fluid and
      vasopressor/inotropic therapy by cardiac output or similar parameters to help in
      early recognition and management of high-risk cardiac surgical patients. With the
      aim of establishing the utility of perioperative GDT using robust clinical and
      biochemical outcomes, we conducted the present study. This multicenter randomized
      controlled study included 130 patients of either sex, with European system for
      cardiac operative risk evaluation >=3 undergoing coronary artery bypass grafting
      on cardiopulmonary bypass. The patients were randomly divided into the control
      and GDT group. All the participants received standardized care; arterial pressure
      monitored through radial artery, central venous pressure (CVP) through a triple
      lumen in the right internal jugular vein, electrocardiogram, oxygen saturation,
      temperature, urine output per hour, and frequent arterial blood gas (ABG)
      analysis. In addition, cardiac index (CI) monitoring using FloTracTM and
      continuous central venous oxygen saturation (ScVO2) using PreSepTM were used in
      patients in the GDT group. Our aim was to maintain the CI at 2.5-4.2 L/min/m2,
      stroke volume index 30-65 ml/beat/m2, systemic vascular resistance index 1500
      2500 dynes/s/cm5/m2, oxygen delivery index 450-600 ml/min/m2, continuous ScVO2
      >70%, and stroke volume variation <10%; in addition to the control group
      parameters such as CVP 6-8 mmHg, mean arterial pressure 90-105 mmHg, normal ABG
      values, oxygen saturation, hematocrit value >30%, and urine output >1 ml/kg/h.
      The aims were achieved by altering the administration of IV fluids and doses of
      inotropes or vasodilators. The data of sixty patients in each group were analyzed
      in view of ten exclusions. The average duration of ventilation (19.89 +/- 3.96
      vs. 18.05 +/- 4.53 h, P = 0.025), hospital stay (7.94 +/- 1.64 vs. 7.17 +/- 1.93
      days, P = 0.025), and Intensive Care Unit (ICU) stay (3.74 +/- 0.59 vs. 3.41 +/-
      0.75 days, P = 0.012) was significantly less in the GDT group, compared to the
      control group. The extra volume added and the number of inotropic dose
      adjustments were significantly more in the GDT group. The two groups did not
      differ in duration of inotropic use, mortality, and other complications. The
      perioperative continuation of GDT affected the early decline in the lactate
      levels after 6 h in ICU, whereas the control group demonstrated a settling
      lactate only after 12 h. Similarly, the GDT group had significantly lower levels
      of brain natriuretic peptide, neutrophil gelatinase-associated lipocalin levels
      as compared to the control. The study clearly depicts the advantage of GDT for a
      favorable postoperative outcome in high-risk cardiac surgical patients.

PMID- 27716693
TI  - Effect of antiplatelet therapy on mortality and acute lung injury in critically
      ill patients: A systematic review and meta-analysis.
AB  - AIM: Platelet function is intricately linked to the pathophysiology of critical
      Illness, and some studies have shown that antiplatelet therapy (APT) may decrease
      mortality and incidence of acute respiratory distress syndrome (ARDS) in these
      patients. Our objective was to understand the efficacy of APT by conducting a
      meta-analysis. MATERIALS AND METHODS: We conducted a meta-analysis using PubMed,
      Central, Embase, The Cochrane Central Register, the ClinicalTrials.gov Website,
      and Google Scholar. Studies were included if they investigated critically ill
      patients receiving antiplatelet therapy and mentioned the outcomes being studied
      (mortality, duration of hospitalization, ARDS, and need for mechanical
      ventilation). RESULTS: We found that there was a significant reduction in all
      cause mortality in patients on APT compared to control (odds ratio [OR]: 0.83;
      95% confidence interval [CI]: 0.70-0.97). Both the incidence of acute lung
      injury/ARDS (OR: 0.67; 95% CI: 0.57-0.78) and need for mechanical ventilation
      (OR: 0.74; 95% CI: 0.60-0.91) were lower in the antiplatelet group. No
      significant difference in duration of hospitalization was observed between the
      two groups (standardized mean difference: -0.02; 95% CI: -0.11-0.07). CONCLUSION:
      Our meta-analysis suggests that critically ill patients who are on APT have an
      improved survival, decreased incidence of ARDS, and decreased need for mechanical
      ventilation.

PMID- 27716695
TI  - Variations of transesophageal echocardiography practices in India: A survey by
      Indian College of Cardiac Anaesthesia.
AB  - CONTEXT: Use of perioperative transesophageal echocardiography (TEE) has expanded
      in India. Despite attempts to standardize the practice of TEE in cardiac surgical
      procedures, variation in practice and application exists. This is the first
      online survey by Indian College of Cardiac Anaesthesia, research and academic
      wing of the Indian Association of Cardiovascular Thoracic Anaesthesiologists
      (IACTA). AIMS: We hypothesized that variations in practice of intraoperative TEE
      exist among centers and this survey aimed at analyzing them. SETTINGS AND DESIGN:
      This is an online survey conducted among members of the IACTA. SUBJECTS AND
      METHODS: All members of IACTA were contacted using online questionnaire fielded
      using SurveyMonkeyTM software. There were 21 questions over four pages evaluating
      infrastructure, documentation of TEE, experience and accreditation of
      anesthesiologist performing TEE, and finally impact of TEE on clinical practice.
      Questions were also asked about national TEE workshop conducted by the IACTA, and
      suggestions were invited by members on overseas training. RESULTS: Response rate
      was 29.7% (382/1222). 53.9% were from high-volume centers (>500 cases annually).
      TEE machine/probe was available to 75.9% of the respondents and those in high
      volume centers had easier (86.9%) access. There was poor documentation of
      preoperative consent (23.3%) as well as TEE findings (66%). Only 18.2% of
      responders were board qualified. Almost 90% of the responders felt surgeons
      respected their TEE diagnosis. Around half of the responders felt that new
      intraoperative findings by TEE were considered in decision-making in most of the
      cases and 70% of the responders reported that surgical plan was altered based on
      TEE finding more than 10 times in the last year. Despite this, only 5% of the
      responders in this survey were monetarily awarded for performing impactful skill
      of TEE. Majority (57%) felt that there is no need for overseas training for
      Indian cardiac anesthesiologists. CONCLUSIONS: In this survey of members of the
      IACTA, use of TEE has increased substantially, but still a lot of variations in
      practice patterns exist in India. There is urgent need for improving TEE
      certification and upgrade documentation standards, motivate use of TTE across all
      centers, promote awareness and usefulness of TEE use among surgical fraternity,
      monitor impact of TEE, and support separate remuneration policy in India.

PMID- 27716696
TI  - Early enteral nutrition therapy in congenital cardiac repair postoperatively: A
      randomized, controlled pilot study.
AB  - BACKGROUND AND OBJECTIVES: Adequate nutritional supplementation in infants with
      cardiac malformations after surgical repair is a challenge. Critically ill
      infants in the early postoperative period are in a catabolic stress. The mismatch
      between estimated energy requirement (EER) and the intake in the postoperative
      period is multifactorial, predisposing them to complications such as immune
      deficiency, more infection, and growth failure. This study aimed to assess the
      feasibility and efficacy of enriched breast milk feed on postoperative recovery
      and growth of infants after open heart surgery. METHODOLOGY: Fifty infants <6
      months of age were prospectively randomized in the trial for enteral nutrition
      (EN) postoperatively from day 1 to 10, after obtaining the Institute Ethics
      Committee's approval. They were equally divided into two groups on the basis of
      the feed they received: Control group was fed with expressed breast milk (EBM;
      0.65 kcal/ml) and intervention group was fed with EBM + energy
      supplementation/fortification with human milk fortifier (7.5 kcal/2 g)/Simyl
      medium-chain triglyceride oil (7.8 kcal/ml). Energy need for each infant was
      calculated as per EER at 90 kcal/kg/day, as the target requirement. The intra-
      and post-operative variables such as cardiopulmonary bypass and aortic cross
      clamp times, ventilation duration, Intensive Care Unit (ICU), and hospital length
      of stay and mortality were recorded. Anthropometric and hematological parameters
      and infection control data were recorded in a predesigned pro forma. Data were
      analyzed using Stata 14.1 software. RESULTS: The duration of mechanical
      ventilation, length of ICU stay (LOIS), length of hospital stay (LOHS), infection
      rate, and mortality rate were lower in the intervention group compared to the
      control group although none of the differences were statistically significant.
      Infants in control group needed mechanical ventilation for about a day more
      (i.e., 153.6 +/- 149.0 h vs. 123.2 +/- 107.0 h; P = 0.20) than those in the
      intervention group. Similarly, infants in control group stayed for longer
      duration in the ICU (13.2 +/- 8.9 days) and hospital (16.5 +/- 9.8 days) as
      compared to the intervention group (11.0 +/- 6.1 days; 14.1 +/- 7.0 days) (P =
      0.14 and 0.17, respectively). The LOIS and LOHS were decreased by 2.2 and 2.4
      days, respectively, in the intervention group compared to control group. The
      infection rate (3/25; 5/25) and mortality rate (1/25; 2/25) were lower in the
      intervention group than those in the control group. The energy intake in the
      intervention group was 40 kcal more (i.e., 127.2 +/- 56.1 kcal vs. 87.1 +/- 38.3
      kcal) than the control group on the 10th postoperative day. CONCLUSIONS: Early
      enteral/oral feeding after cardiac surgery is feasible and recommended. In
      addition, enriching the EBM is helpful in achieving the maximum possible calorie
      intake in the postoperative period. EN therapy might help in providing adequate
      nutrition, and it decreases ventilation duration, infection rate, LOIS, LOHS, and
      mortality.

PMID- 27716697
TI  - Effect of prophylaxis of magnesium sulfate for reduction of postcardiac surgery
      arrhythmia: Randomized clinical trial.
AB  - BACKGROUND: Arrhythmia is a common complication after heart surgery and is a
      major source of morbidity and mortality. AIMS: This study aimed to study the
      effect of magnesium sulfate (MgSO4) for reduction of postcardiac surgery
      arrhythmia. SETTING AND DESIGN: This study is performed in the cardiac operating
      room and Intensive Care Unit (ICU) of Shahid Madani Hospital of Tabriz (Iran)
      between January 1, 2014, and September 30, 2014. This study is a double-blind,
      randomized controlled trial. MATERIALS AND METHODS: In Group 1 (group magnesium
      [Mg]), eighty patients received 30 mg/kg MgSO4in 500 cc normal saline and in
      Group 2 (group control), eighty patients received 500 cc normal saline alone.
      STATISTICAL ANALYSIS: The occurrence of arrhythmia was compared between groups by
      Chi-square and Fisher's exact test. In addition, surgical time, length of ICU
      stay, and length of hospital stay were compared by independent t-test. P< 0.05
      was considered as significant. RESULTS: There was a significant difference in the
      incidence of arrhythmia between two groups (P = 0.037). The length of ICU stay
      was 3.4 +/- 1.4 and 3.73 +/- 1.77 days in group MgSO4and control group,
      respectively, and there was no statistically significant difference between two
      groups (P = 0.2). CONCLUSION: Mg significantly decreases the incidence of all
      type of postcardiac surgery arrhythmia and hospital length of stay at patients
      undergo cardiac surgery. We offer prophylactic administration of Mg at patients
      undergo cardiac surgery.

PMID- 27716698
TI  - Hyperlactatemia in patients undergoing adult cardiac surgery under
      cardiopulmonary bypass: Causative factors and its effect on surgical outcome.
AB  - OBJECTIVES OF THE STUDY: To identify the factors causing high lactate levels in
      patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) and to
      assess the association between high blood lactate levels and postoperative
      morbidity and mortality. METHODS: A retrospective observational study including
      370 patients who underwent cardiac surgeries under cardiopulmonary bypass. The
      patients were divided into 2 groups based on serum lactate levels; those with
      serum lactate levels greater than or equal to 4 mmol/L considered as
      hyperlactatemia and those with serum lactate levels less than 4 mmol/L. Blood
      lactate samples were collected intraoperatively and postoperatively in the ICU.
      Preoperative and intraoperative risk factors for hyperlactatemia were identified
      using the highest intraoperative value of lactate. The postoperative morbidity
      and mortality associated with hyperlactatemia was studied using the overall
      (intraoperative and postoperative values) peak lactate levels. Preoperative
      clinical data, perioperative events and postoperative morbidity and mortality
      were recorded. RESULTS: Intraoperative peak blood lactate levels of 4.0 mmol/L or
      more were present in 158 patients (42.7%). Females had higher peak intra
      operative lactate levels (P = 0.011). There was significant correlation between
      CPB time (Pearson correlation coefficient r = 0.024; P = 0.003) and aortic cross
      clamp time (r = 0.02, P = 0.007) with peak intraoperative blood lactate levels.
      Patients with hyperlactatemia had significantly higher rate of postoperative
      morbidity like atrial fibrillation (19.9% vs. 5.3%; P = 0.004), prolonged
      requirement of inotropes (34% vs. 11.8%; P = 0.001), longer stay in the ICU (P =
      0.013) and hospital (P = 0.001). CONCLUSIONS: Hyperlactatemia had significant
      association with post-operative morbidity. Detection of hyperlactatemia in the
      perioperative period should be considered as an indicator of inadequate tissue
      oxygen delivery and must be aggressively corrected.

PMID- 27716699
TI  - Perioperative management of patients with left ventricular assist devices
      undergoing noncardiac surgery.
AB  - AIM: The aim of this study was to describe our institutional experience,
      primarily with general anesthesiologists consulting with cardiac
      anesthesiologists, caring for left ventricular assist device (LVAD) patients
      undergoing noncardiac surgery. MATERIALS AND METHODS: This is a retrospective
      review of the population of patients with LVADs at a single institution
      undergoing noncardiac procedures between 2009 and 2014. Demographic,
      perioperative, and procedural data collected included the type of procedure
      performed, anesthetic technique, vasopressor requirements, invasive monitors
      used, anesthesia provider type, blood product management, need for postoperative
      intubation, postoperative disposition and length of stay, and perioperative
      complications including mortality. STATISTICAL ANALYSIS: Descriptive statistics
      for categorical variables are presented as frequency distributions and
      percentages. Continuous variables are expressed as mean +/- standard deviation
      and range when applicable. RESULTS: During the study, 31 patients with LVADs
      underwent a total of 74 procedures. Each patient underwent an average of 2.4
      procedures. Of the total number of procedures, 48 (65%) were upper or lower
      endoscopies. Considering all procedures, 81% were performed under monitored
      anesthesia care (MAC). Perioperative care was provided by faculty outside of the
      division of cardiac anesthesia in 62% of procedures. Invasive blood pressure
      monitoring was used in 27 (36%) procedures, and a central line, peripherally
      inserted central catheter or midline was in place preoperatively and used
      intraoperatively for 38 (51%) procedures. Vasopressors were not required in the
      majority (65; 88%) of procedures. There was one inhospital mortality secondary to
      multiorgan failure; 97% of patients survived to discharge after their procedure.
      CONCLUSION: At our institution, LVAD patients undergoing noncardiac procedures
      most frequently require endoscopy. These procedures can frequently be done safely
      under MAC, with or without consultation by a cardiac anesthesiologist.

PMID- 27716700
TI  - The formation of bronchocutaneous fistulae due to retained epicardial pacing
      wires: A literature review.
AB  - Temporary epicardial pacing wires during open-heart surgery are routinely used
      both for diagnostic and treatment purposes. In complicated cases where patients
      are unstable or the wires are difficult to remove, the pacing wires are cut at
      the skin level and allowed to retract by themselves. This procedure rarely causes
      complications. However, there have been cases reporting that retained pacing
      wires are linked to the formation of sterno-bronchial fistulae, which may present
      a while after the date of operation and are usually infected. This review aims to
      study the cases presenting sterno-bronchial fistulae due to retained epicardial
      pacing wires and to highlight the important factors associated with these. It is
      important to note these complications, as fistulae may cause a variety of
      problems to the patient if undiagnosed and left untreated. With the aid of scans
      such as fistulography, fistulae can be identified and treated and will improve
      the patients' health dramatically.

PMID- 27716702
TI  - Global end-diastolic volume an emerging preload marker vis-a-vis other markers -
      Have we reached our goal?
AB  - A reliable estimation of cardiac preload is helpful in the management of severe
      circulatory dysfunction. The estimation of cardiac preload has evolved from
      nuclear angiography, pulmonary artery catheterization to echocardiography, and
      transpulmonary thermodilution (TPTD). Global end-diastolic volume (GEDV) is the
      combined end-diastolic volumes of all the four cardiac chambers. GEDV has been
      demonstrated to be a reliable preload marker in comparison with traditionally
      used pulmonary artery catheter-derived pressure preload parameters. Recently, a
      new TPTD system called EV1000TM has been developed and introduced into the
      expanding field of advanced hemodynamic monitoring. GEDV has emerged as a better
      preload marker than its previous conventional counterparts. The advantage of it
      being measured by minimum invasive methods such as PiCCOTM and newly developed
      EV1000TM system makes it a promising bedside advanced hemodynamic parameter.

PMID- 27716701
TI  - Cardiac surgery-associated acute kidney injury.
AB  - Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-recognized
      complication resulting with the higher morbid-mortality after cardiac surgery. In
      its most severe form, it increases the odds ratio of operative mortality 3-8
      fold, length of stay in the Intensive Care Unit and hospital, and costs of care.
      Early diagnosis is critical for an optimal treatment of this complication. Just
      as the identification and correction of preoperative risk factors, the use of
      prophylactic measures during and after surgery to optimize renal function is
      essential to improve postoperative morbidity and mortality of these patients.
      Cardiopulmonary bypass produces an increased in tubular damage markers. Their
      measurement may be the most sensitive means of early detection of AKI because
      serum creatinine changes occur 48 h to 7 days after the original insult. Tissue
      inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7
      are most promising as an early diagnostic tool. However, the ideal noninvasive,
      specific, sensitive, reproducible biomarker for the detection of AKI within 24 h
      is still not found. This article provides a review of the different perspectives
      of the CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers,
      classification, postoperative management, and treatment. We searched the
      electronic databases, MEDLINE, PubMed, EMBASE using search terms relevant
      including pathogenesis, risk factors, diagnosis, biomarkers, classification,
      postoperative management, and treatment, in order to provide an exhaustive review
      of the different perspectives of the CSA-AKI.

PMID- 27716705
TI  - Windsock deformity of interatrial septum.
AB  - Classical "Windsock deformity" is associated with ruptured aneurysmal sinus of
      Valsalva. The echocardiographic definition for Atrial septal aneurysm (ASA) in
      children based on dimensions is lacking. Rupture of an ASA, though uncommon, may
      lead to cardiac failure due to acute RV volume overload. An untreated ASA may be
      complicated with thrombus formation.

PMID- 27716704
TI  - Role of hybrid operating room in surgery for the right atrial thrombus, pulmonary
      thrombi, and ventricular septal rupture after myocardial infarction.
AB  - Free-floating right heart thrombi are uncommon and need emergency treatment in
      view of their tendency to dislodge and cause pulmonary embolism. We report a
      successful surgical management of a patient who had large mobile right atrial
      thrombus, bilateral pulmonary thrombi, coronary artery disease, and
      postmyocardial infarction ventricular septal rupture (VSR). The patient underwent
      coronary angiography, inferior vena cava filter placement, removal of thrombi
      from the right atrium and pulmonary arteries, repair of VSR, and coronary artery
      bypass graft surgery in a hybrid operating room.

PMID- 27716703
TI  - Strategies for blood conservation in pediatric cardiac surgery.
AB  - Cardiac surgery accounts for the majority of blood transfusions in a hospital.
      Blood transfusion has been associated with complications and major adverse events
      after cardiac surgery. Compared to adults it is more difficult to avoid blood
      transfusion in children after cardiac surgery. This article takes into account
      the challenges and emphasizes on the various strategies that could be
      implemented, to conserve blood during pediatric cardiac surgery.

PMID- 27716706
TI  - Double valve replacement in a patient with implantable cardioverter defibrillator
      with severe left ventricular dysfunction.
AB  - Recent data from landmark trials suggest that the indications for cardiac pacing
      and implantable cardioverter defibrillators (ICDs) are set to expand to include
      heart failure, sleep-disordered breathing, and possibly routine implantation in
      patients with myocardial infarction and poor ventricular function.[1] This will
      inevitably result in more patients with cardiac devices undergoing surgeries.
      Perioperative electromagnetic interference and their potential effects on ICDs
      pose considerable challenges to the anesthesiologists.[2] We present a case of a
      patient with automatic ICD with severe left ventricular dysfunction posted for
      double valve replacement.

PMID- 27716707
TI  - Left ventricular mass: A tumor or a thrombus diagnostic dilemma.
AB  - Left ventricular (LV) mass is a rare condition, of which the most common is
      thrombus. Echocardiography is a very useful modality of investigation to evaluate
      the LV mass. We are reporting a case of LV mass presenting with neurological
      symptom. The diagnosis of this mass was dilemma as the echocardiographic features
      were favoring tumor as well as thrombi. Mass (a) measuring 3.8 cm * 1.9 cm
      attached to the left ventricle apex appeared to be pedunculated tumor and mass
      (b) measuring 2.4 cm * 1.8 cm attached to the chordae of anterior mitral leaflet
      resembled a thrombus or an embolized tumor entangled in the chordae. A
      differential diagnosis for the LV mass is thrombus, tumors such as fibroma, and
      vegetation. Preoperative detection of a thrombus leads to an alteration in
      surgical steps. A large and mobile thrombus with or without a hemodynamic
      alteration is an indication for surgical removal to prevent stroke, myocardial
      infarction, mesenteric ischemia, renal infarction, gangrene of the limbs, and
      mortality.

PMID- 27716708
TI  - Transesophageal echo diagnosis of perioperative unusual transient left
      ventricular apical ballooning syndrome.
AB  - Stress cardiomyopathy, or Takotsubo syndrome, is a widely recognized cardiac
      pathology with a clinical presentation similar to acute coronary syndrome and
      related to physical or emotional stress. Perioperatively, it is challenging to
      identify it given the variety of forms and scenarios in which it can present. We
      describe a 22-year-old patient with an atypical presentation of Takotsubo
      syndrome during anesthesia induction, which highlights the usefulness of
      transesophageal echocardiography for the initial diagnosis.

PMID- 27716710
TI  - Transesophageal echocardiography-guided thrombectomy of intracardiac renal cell
      carcinoma without cardiopulmonary bypass.
AB  - Advanced renal cell carcinoma (RCC) resection has important anesthetic management
      implications, particularly when tumor extends, suprahepatic, into the right
      atrium. Use of transesophageal echocardiogram (TEE) is essential in identifying
      tumor extension and guiding resection. Latest surgical approach avoids venovenous
      and cardiopulmonary bypass yet requires special precautions and interventions on
      the anesthesiologist's part. We present a case of Level IV RCC resected without
      cardiopulmonary bypass and salvaged by TEE guidance and detection of residual
      intracardiac tumor.

PMID- 27716709
TI  - Valve-in-valve-in homograft: A case of a repeat transcatheter aortic valve
      replacement in a patient with an aortic homograft.
AB  - In recent years, the use of transcatheter aortic valve replacement (TAVR) has
      extended beyond the treatment of native aortic valve stenosis in patients with
      high surgical risk. TAVR is increasingly being performed for bioprosthetic aortic
      valve failure, i.e., the valve-in-valve (VIV) procedure. Establishing the success
      of a VIV procedure can be challenging in these cases. Furthermore, the limited
      availability of prostheses sizes further complicates the management of these
      patients. We present an unusual case of a repeat TAVR in a patient who previously
      had a VIV procedure in an aortic homograft.

PMID- 27716711
TI  - Critical decision of operability in congenital heart disease patient with severe
      pulmonary hypertension.
AB  - Repair of congenital heart disease in the presence of high pulmonary pressure has
      always been a contentious issue. Pulmonary vascular resistance (PVR) is
      considered important for establishing operability in these patients. However, PVR
      estimation is not always accurate and cannot solely be relied upon to make
      critical decision of operability. Clinical examination, chest X-ray, and
      echocardiography are also important indicators of pulmonary vascular disease.
      Knowledge of pits and falls of each investigation is important for appropriate
      management in these patients. We present a case report of successfully operated,
      6-year-old child with anomalous origin of the right pulmonary artery from aorta,
      deemed inoperable on the basis of PVR estimation.

PMID- 27716712
TI  - A lethal tension pneumothorax during minimally invasive coronary artery bypass
      surgery: Can transesophageal echocardiography pick it?
AB  - Minimally invasive cardiac surgery is establishing itself as the standard of care
      across the world. MICS CABG is currently performed in only a few centers.
      Hemodynamics disturbances are peculiar during MICS CABG due to space constraints.
      We report a 70-year-old man who underwent MICS CABG who developed tension
      pneumothorax during revascularization that was diagnosed in a novel way.

PMID- 27716713
TI  - Anesthetic management of patent ductus arteriosus in adults.
AB  - Patent ductus arteriosus (PDA) is an extracardiac left to right shunt. It should
      be corrected at an early age, but some patients may survive into adult life even
      without repair. Anesthetic management for adult patients with PDA poses many
      challenges for the anesthesiologist due to alterations in the cardiopulmonary
      physiology. We report successful anesthesia management of a case of an adult
      patient of PDA with moderate pulmonary artery hypertension with infective
      endarteritis (two large mobile vegetations at the pulmonary end of the duct).

PMID- 27716714
TI  - Aortic valve homograft for revision surgery - transesophageal echocardiography
      considerations.
AB  - Aortic root surgical anatomy and knowledge of the various homograft implantation
      techniques is of paramount importance to the attending anesthesiologist for
      echocardiographic correlation, estimation and accurately predicting aortic
      annular dimensions for the valve replacement in a case of diseased homograft.

PMID- 27716715
TI  - Symmetrical peripheral gangrene associated with cardiac surgery.

PMID- 27716716
TI  - Sepsis in heart transplant recipients: Is the new definition applicable?

PMID- 27716717
TI  - Catatonic stupor after off-pump coronary artery bypass grafting.

PMID- 27716719
TI  - Airway management: High flow nasal oxygenation.

PMID- 27716718
TI  - Arterialization of central venous pressure waveform.

PMID- 27716720
TI  - The manuscript review process: What do editors do?

PMID- 27716721
TI  - Guidelines for the management of Stevens-Johnson syndrome/toxic epidermal
      necrolysis: An Indian perspective.
AB  - BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are severe,
      life-threatening mucocutaneous adverse drug reactions with a high morbidity and
      mortality that require immediate medical care. The various immunomodulatory
      treatments include systemic corticosteroids, cyclosporine, intravenous
      immunoglobulin, cyclophosphamide, plasmapheresis and tumor necrosis factor-alpha
      inhibitors. AIM: The ideal therapy of Stevens-Johnson syndrome/toxic epidermal
      necrolysis still remains a matter of debate as there are only a limited number of
      studies of good quality comparing the usefulness of different specific
      treatments. The aim of this article is to comprehensively review the published
      medical literature and frame management guidelines suitable in the Indian
      perspective. METHODS: The Indian Association of Dermatologists, Venereologists
      and Leprologists (IADVL) assigned the task of preparing these guidelines to its
      special interest group on cutaneous adverse drug reactions. The group performed a
      comprehensive English language literature search for management options in
      Stevens-Johnson syndrome/toxic epidermal necrolysis across multiple databases
      (PubMed, EMBASE, MEDLINE and Cochrane) for keywords (alone and in combination)
      and MeSH items such as "guidelines," "Stevens-Johnson syndrome," "toxic epidermal
      necrolysis," "corticosteroids," "intravenous immunoglobulin," "cyclosporine" and
      "management." The available evidence was evaluated using the strength of
      recommendation taxonomy and graded using a three-point scale. A draft of clinical
      recommendations was developed on the best available evidence which was also
      scrutinized and critically evaluated by the IADVL Academy of Dermatology. Based
      on the inputs received, this final consensus statement was prepared. RESULTS: A
      total of 104 articles (meta-analyses, prospective and retrospective studies,
      reviews [including chapters in books], previous guidelines [including Indian
      guidelines of 2006] and case series) were critically evaluated and the evidence
      thus gathered was used in the preparation of these guidelines. RECOMMENDATIONS:
      This expert group recommends prompt withdrawal of the culprit drug, meticulous
      supportive care, and judicious and early (preferably within 72 h) initiation of
      moderate to high doses of oral or parenteral corticosteroids (prednisolone 1-2
      mg/kg/day or equivalent), tapered rapidly within 7-10 days. Cyclosporine (3-5
      mg/kg/day) for 10-14 days may also be used either alone, or in combination with
      corticosteroids. Owing to the systemic nature of the disease, a multidisciplinary
      approach in the management of these patients is helpful.

PMID- 27716722
TI  - Biologics or biosimilars: What is the difference?

PMID- 27716723
TI  - Author reply: Biologics or biosimilars: What is the difference?

PMID- 27716724
TI  - Selenium toxicity: A rare diagnosis.

PMID- 27716725
TI  - Imatinib mesylate-induced pseudoporphyria in a patient with chronic myeloid
      leukemia.

PMID- 27716726
TI  - Is there any relationship between cardiopulmonary capacity and cardiovascular
      mechanics in coronary artery disease?

PMID- 27716729
TI  - Survival in individuals living with HIV.

PMID- 27716727
TI  - The Differential Impact of Emphysema on Respiratory Symptoms and 6-Minute Walk
      Distance in HIV Infection.
AB  - BACKGROUND: Emphysema is more prevalent in HIV-infected (HIV+) patients
      independent of smoking behavior. Nonetheless, health effects of emphysema in this
      population are poorly understood. We determined whether emphysema is associated
      with a greater burden of pulmonary symptoms and a lower 6-minute walk distance
      (6MWD) in HIV+ compared with HIV-uninfected (HIV-) subjects. METHODS: We
      performed a cross-sectional analysis of 170 HIV+ and 153 HIV- subjects in the
      Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. Subjects
      completed a self-assessment of respiratory symptoms, pulmonary function testing,
      and 6MWD testing as well as a chest computed tomography to determine emphysema
      severity. We used regression models to determine the association of emphysema
      with respiratory symptoms and 6MWD in HIV+ subjects and compared this to HIV-
      subjects. RESULTS: Models stratified by HIV status demonstrated an association
      between >10% radiographic emphysema and chronic cough and/or phlegm and 6MWD in
      HIV+ subjects. These associations persisted among the subset without airflow
      obstruction: those with emphysema had 4.2 (95% confidence interval: 1.3 to 14)
      times the odds of chronic cough and/or phlegm and walked 60 m (95% confidence
      interval: 26 to 93) less distance than those without emphysema. There was no
      association between >10% emphysema and symptoms or 6MWD in HIV- subjects.
      CONCLUSIONS: In our cohort, >10% radiographic emphysema was associated with
      chronic cough and/or phlegm and lower 6MWD in HIV+ but not HIV- subjects. These
      findings were robust even among HIV+ subjects with milder forms of emphysema and
      those without airflow obstruction, highlighting the clinical impact of emphysema
      in these patients.

PMID- 27716731
TI  - Health and survival of HIV perinatally exposed but uninfected children born to
      HIV-infected mothers.
AB  - PURPOSE OF REVIEW: The number of HIV-exposed but uninfected (HEU) infants exposed
      to both HIV and multiple antiretroviral drugs in utero and during prolonged
      breastfeeding is increasing in low-income countries where HIV prevalence is the
      highest. We review recent evidence on the effects of perinatal/postnatal exposure
      to maternal HIV and combined antiretroviral therapy (cART) on health outcomes of
      HEU children (mitochondrial and metabolic toxicity, adverse pregnancy outcomes,
      neurodevelopment, growth, infectious morbidity, and mortality). RECENT FINDINGS:
      Several studies have reported ART-associated mitochondrial toxicity and metabolic
      disorders with conflicting results on adverse pregnancy outcomes, underscoring
      the need to conduct further investigations on these questions. Studies about
      congenital abnormalities report no significant differences between HEU exposed to
      ART and HIV-unexposed (HUU) children. Updated French data showed no significant
      difference in cancer incidence between HEU cART-exposed children and the general
      paediatric population. Furthermore, HEU children exposed to maternal cART have
      modest but significant impairment of development and a higher risk of growth
      impairment. Finally, HEU have higher risks of infections (mainly low respiratory
      tract infections and diarrhoea) and malaria than HUU children, particularly in
      children not breastfed or after early weaning. Higher mortality risk from
      infectious disease is reported in HEU compared to HUU children. SUMMARY: As we
      move toward the elimination of mother-to-child transmission of HIV, HEU children
      are an emerging population whose health outcomes remain to be fully described.
      Future large cohorts of HEU children using careful comparison groups of HUU in
      the post-ART era are needed to better understand their long-term health outcomes.

PMID- 27716732
TI  - Effect of coinfection with hepatitis C virus on survival of individuals with HIV
      1 infection.
AB  - PURPOSE OF REVIEW: Hepatitis C virus (HCV) coinfection is a common and an
      important comorbidity in HIV infection. We review current trends in mortality and
      the potential for early combination antiretroviral therapy (cART) and HCV therapy
      to improve survival in coinfected patients. RECENT FINDINGS: HIV/HCV coinfection
      increases risk of death from all causes, and from liver disease and harmful drug
      use in particular. There is growing evidence for a direct role of HIV in liver
      fibrogenesis and for cART to decrease the risk of dying from liver disease in
      coinfected persons. Sustained virologic responses after HCV treatment greatly
      impact mortality by reducing rates of hepatic decompensation, hepatocellular
      carcinoma and death from liver-related and nonliver-related causes by at least
      50%, but treatment uptake has been low so far. Recent epidemiologic studies do
      suggest that liver-related mortality is declining in recent calendar periods;
      however, methodological limitations of currently available studies are important.
      SUMMARY: Early cART and wider HCV treatment have the potential to markedly reduce
      HCV-related mortality and thus increase survival overall for HIV-infected
      populations. However, HCV treatment will need to be greatly scaled up. Given the
      complex nature of the populations affected, future studies will need to be
      carefully designed and controlled to rigorously evaluate the impact of these
      revolutionary therapies on survival.

PMID- 27716730
TI  - Survival of HIV-1 vertically infected children.
AB  - PURPOSE OF REVIEW: It is 20 years since the start of the combination
      antiretroviral therapy (cART) era and more than 10 years since cART scale-up
      began in resource-limited settings. We examined survival of vertically HIV
      infected infants and children in the cART era. RECENT FINDINGS: Good survival has
      been achieved on cART in all settings with up to 10-fold mortality reductions
      compared with before cART availability. Although mortality risk remains high in
      the first few months after cART initiation in young children with severe disease,
      it drops rapidly thereafter even for those who started with advanced disease, and
      longer term mortality risk is low. However, suboptimal retention on cART in
      routine programs threatens good survival outcomes and even on treatment children
      continue to experience high comorbidity risk; infections remain the major cause
      of death. Interventions to address infection risk include a cotrimoxazole
      prophylaxis, isoniazid preventive therapy, routine childhood and influenza
      immunization, and improving maternal survival. SUMMARY: Pediatric survival has
      improved substantially with cART and HIV-infected children are aging into
      adulthood. It is important to ensure access to diagnosis and early cART, good
      program retention as well as optimal comorbidity prophylaxis and treatment to
      achieve the best possible long-term survival and health outcomes for vertically
      infected children.

PMID- 27716734
TI  - Lessons from acute HIV infection.
AB  - PURPOSE OF REVIEW: Understanding the characteristics of transmission during acute
      HIV infection (AHI) may inform targets for vaccine-induced immune interdiction.
      Individuals treated in AHI with a small HIV reservoir size may be ideal
      candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic
      control after treatment interruption). RECENT FINDINGS: The AHI period is brief
      and peak viremia predicts a viral set point that occurs 4-5 weeks following
      infection. Robust HIV-specific CD8 T-cell responses lower viral set points.
      Phylogenetic analyses of founder viruses demonstrated unique bottleneck
      selections and specific genetic signatures to optimize for high-fitness variants
      and successful transmission events. HIV clades, route of transmission and the
      presence of minor variants may affect vaccine protection. Antiretroviral
      treatment in AHI results in smaller HIV reservoir size, better CD4 T-cell
      recovery and fewer virus escapes. SUMMARY: The knowledge of untreated and treated
      AHI informs the development of vaccines, in that preventive vaccines will require
      broad coverage for multiple clades and antigenic variants associated with unique
      bottleneck selections. Vaccines that help the host to control viremia could
      minimize onward transmission. Therapeutic HIV vaccines aimed at HIV remission
      should be studied in early-treated individuals who have few or no viral escape
      mutants and a more preserved immune system.

PMID- 27716735
TI  - Glaucocalyxin A Ameliorates Myocardial Ischemia-Reperfusion Injury in Mice by
      Suppression of Microvascular Thrombosis.
AB  - BACKGROUND The aim of this study was to evaluate the cardio-protective roles of
      glaucocalyxin A (GLA) in myocardial ischemia-reperfusion injury and to explore
      the underlying mechanism. MATERIAL AND METHODS Myocardial ischemia-reperfusion in
      wild-type C57BL/6J mice was induced by transient ligation of the left anterior
      descending artery. GLA or vehicle (solvent) was administrated intraperitoneally
      to the mice before reperfusion started. After 24 h of myocardial reperfusion,
      ischemic size was revealed by Evans blue/TTC staining. Cardiac function was
      evaluated by echocardiography and microvascular thrombosis was assessed by
      immunofluorescence staining of affected heart tissue. We also measured the
      phosphorylation of AKT, ERK, P-GSK-3beta, and cleaved caspase 3 in the
      myocardium. RESULTS Compared to the solvent-treated control group, GLA
      administration significantly reduced infarct size (GLA 13.85+/-2.08% vs. Control
      18.95+/-0.97%, p<0.05) and improved left ventricular ejection fraction (LVEF)
      (GLA 53.13+/-1.11% vs. Control 49.99+/-1.25%, p<0.05) and left ventricular
      fractional shortening (LVFS) (28.34+/-0.71% vs. Control 25.11+/-0.74%, p<0.05) in
      mice subjected to myocardial ischemia-reperfusion. GLA also attenuated
      microvascular thrombosis (P<0.05) and increased the phosphorylation of pro
      survival kinase AKT (P<0.05) and GSK-3beta (P<0.05) in the myocardium upon
      reperfusion injury. CONCLUSIONS Administration of GLA before reperfusion
      ameliorates myocardial ischemia-reperfusion injury in mice. The cardio-protective
      roles of GLA may be mediated through the attenuation of microvascular thrombosis.

PMID- 27716736
TI  - Banding ligation or beta-blockers for primary prevention of variceal bleeding?
AB  - Variceal bleeding is one of the most serious complications of liver cirrhosis.
      Nonselective beta-blockers and endoscopic ligation are considered effective
      strategies for primary prevention of variceal bleeding, but there is no consensus
      about which alternative constitutes the best option. Searching in Epistemonikos
      database, which is maintained by screening 30 databases, we identified seven
      systematic reviews including 21 randomized controlled trials addressing the
      question of this article. We combined the evidence using meta-analysis and
      generated a summary of findings following the GRADE approach. We concluded
      variceal ligation probably decreases the risk of variceal bleeding and it is
      associated to less adverse effects when compared with nonselective beta blockers,
      although probably there is no difference in terms of mortality.

PMID- 27716737
TI  - Echinococcosis and cysticercosis: neglected diseases in Chile.

PMID- 27716738
TI  - A 2016 panorama of Helicobacter pylori infection: key messages for clinicians.
AB  - The discovery that the bacterium Helicobacter pylori (H. pylori) lives in the
      stomach has rendered out-of-date the concept of inhospitality of the gastric
      environment. H. pylori is able to survive in this organ through mechanisms of
      acid resistance and colonization factors. The prevalence of H. pylori infection
      varies depending on age, socioeconomic class, and country. Currently, in the
      context of a decreased trend in H. pylori prevalence, it is estimated that about
      50% of the world's human population are carriers of the microorganism, with a
      higher rate in developing countries than in developed countries. In this review,
      the authors provide an overview on the current status of knowledge on the
      clinical aspects of H. pylori infection, with a focus on diagnostic and
      therapeutic challenges. In particular, the choice of the test to diagnose H.
      pylori infection, defined as invasive or non-invasive based on the need or not of
      biopsy specimens obtained during an endoscopy, depends on the clinical context.
      Regarding bacterial eradication, it is important that treatment should be decided
      locally on the basis of local antibiotic usage, documented antibiotic resistance
      and outcome data. For patients having previously received a clarithromycin
      containing regimen, this drug should be avoided as a second-line therapy. In this
      case, the tailored therapy (to test clarithromycin susceptibility before
      prescribing drugs) or the so-called quadruple therapy, and triple levofloxacin
      based therapy should be proposed. Rifabutin- and furazolidone-based treatments
      should be reserved for further treatment.

PMID- 27716739
TI  - The effect of a functional appliance in the management of temporomandibular joint
      disorders in patients with juvenile idiopathic arthritis.
AB  - BACKGROUND: Patients affected by juvenile idiopathic arthritis (JIA) may have
      several craniofacial growth disturbances and involvements at the
      temporomandibular joint (TMJ). The objectives of the present study were to
      evaluate the clinical effectiveness of functional therapy used to reduce
      asymmetry of mandibular growth and TMJ disorder in patients with JIA. METHODS: By
      a retrospective longitudinal design, a cohort of 54 patients with JIA (mean age,
      13.2+/-3.7 years; range, 5-17.7 years) and with TMJ involvements was enrolled in
      the study. Each patient, following the collection of clinical parameters, was
      treated for 24 months with a functional appliance individually customized by
      acrylic resin and resilient stainless steel with posterior and anterior metallic
      bite planes preventing the teeth from intercuspal contact. To evaluate
      differences before (T0) and after therapy (T1) of the clinical TMJ parameters,
      the statistical analysis by the chi2 Test was performed. RESULTS: All the
      patients completed successfully the study. In patients with JIA, the use of a
      functional appliance determined a statistically significant difference of the
      pain during jaw movement, maximal mouth opening, TMJ sounds and crepitations
      (P<0.001) and TMJ click, significantly reduced at T1 (P<0.05). CONCLUSIONS: The
      use of an orthodontic functional appliance determined a significant improvement,
      at 24 months, in many TMJ signs and symptoms in patients affected by JIA and with
      TMJ disorders. This study suggests that children and adolescents with JIA which
      presented either unilateral or bilateral moderate to severe TMJ involvement, if
      not treated, should be develop severe disturbances during growing.

PMID- 27716740
TI  - High levels of periostin correlate with increased fracture rate, diffuse MRI
      pattern, abnormal bone remodeling and advanced disease stage in patients with
      newly diagnosed symptomatic multiple myeloma.
AB  - Periostin is an extracellular matrix protein that is implicated in the biology of
      normal bone remodeling and in different cancer cell growth and metastasis.
      However, there is no information on the role of periostin in multiple myeloma
      (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the
      bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM)
      patients and in the serum of 23 monoclonal gammopathy of undetermined
      significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau
      phase post-first-line therapy, 30 patients at first relapse and 30 healthy
      controls. We found high levels of periostin in the supernatants of myeloma cell
      lines compared with ovarian cancer cell lines that were not influenced by the
      incubation with the stromal cell line HS5. In NDMM patients the bone marrow
      plasma periostin was almost fourfold higher compared with the serum levels of
      periostin and correlated with the presence of fractures and of diffuse magnetic
      resonance imaging pattern of marrow infiltration. Serum periostin was elevated in
      NDMM patients compared with healthy controls, MGUS and SMM patients and
      correlated with advanced disease stage, high lactate dehydrogenase, increased
      activin-A, increased bone resorption and reduced bone formation. Patients at
      first relapse had also elevated periostin compared with healthy controls, MGUS
      and SMM patients, while even patients at the plateau phase had elevated serum
      periostin compared with healthy controls. These results support an important role
      of periostin in the biology of myeloma and reveal periostin as a possible target
      for the development of antimyeloma drugs.

PMID- 27716742
TI  - Cytotoxic efficacy of filanesib and melphalan combination is governed by sequence
      of treatment in human myeloma cells.

PMID- 27716741
TI  - Expression of CALR mutants causes mpl-dependent thrombocytosis in zebrafish.
AB  - CALR mutations are identified in about 30% of JAK2/MPL-unmutated
      myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET) and
      primary myelofibrosis. Although the molecular pathogenesis of CALR mutations
      leading to MPNs has been studied using in vitro cell lines models, how mutant
      CALR may affect developmental hematopoiesis remains unknown. Here we took
      advantage of the zebrafish model to examine the effects of mutant CALR on early
      hematopoiesis and model human CALR-mutated MPNs. We identified three zebrafish
      genes orthologous to human CALR, referred to as calr, calr3a and calr3b. The
      expression of CALR-del52 and CALR-ins5 mutants caused an increase in the
      hematopoietic stem/progenitor cells followed by thrombocytosis without affecting
      normal angiogenesis. The expression of CALR mutants also perturbed early
      developmental hematopoiesis in zebrafish. Importantly, morpholino knockdown of
      mpl but not epor or csf3r could significantly attenuate the effects of mutant
      CALR. Furthermore, the expression of mutant CALR caused jak-stat signaling
      activation in zebrafish that could be blocked by JAK inhibitors (ruxolitinib and
      fedratinib). These findings showed that mutant CALR activates jak-stat signaling
      through an mpl-dependent mechanism to mediate pathogenic thrombopoiesis in
      zebrafish, and illustrated that the signaling machinery related to mutant CALR
      tumorigenesis are conserved between human and zebrafish.

PMID- 27716743
TI  - Ruxolitinib therapy and telomere length in myelofibrosis.

PMID- 27716744
TI  - Mechanism of TAp73 inhibition by DeltaNp63 and structural basis of p63/p73 hetero
      tetramerization.
AB  - Members of the p53 tumor-suppressor family are expressed as multiple isoforms.
      Isoforms with an N-terminal transactivation domain are transcriptionally active,
      while those ones lacking this domain often inhibit the transcriptional activity
      of other family members. In squamous cell carcinomas, the high expression level
      of DeltaNp63alpha inhibits the tumor-suppressor function of TAp73beta. This can
      in principle be due to blocking of the promoter or by direct interaction between
      both proteins. p63 and p73 can hetero-oligomerize through their tetramerization
      domains and a hetero-tetramer consisting of two p63 and two p73 molecules is
      thermodynamically more stable than both homo-tetramers. Here we show that cells
      expressing both p63 and p73 exist in mouse epidermis and hair follicle and that
      hetero-tetramer complexes can be detected by immunoprecipitation in
      differentiating keratinocytes. Through structure determination of the hetero
      tetramer, we reveal why this hetero-tetramer is the thermodynamically preferred
      species. We have created mutants that exclusively form either hetero-tetramers or
      homo-tetramers, allowing to investigate the function of these p63/p73 hetero
      tetramers. Using these tools, we show that inhibition of TAp73beta in squamous
      cell carcinomas is due to promoter squelching and not direct interaction.

PMID- 27716745
TI  - The degradation of EZH2 mediated by lncRNA ANCR attenuated the invasion and
      metastasis of breast cancer.
AB  - EZH2 (the Enhancer of Zeste Homolog 2), as a key epigenetic regulator and EMT
      inducer, participates in a variety of cancer metastasis. EZH2 stability is
      regulated by several types of post-translational modifications (PTMs).The long
      non-coding RNAs (lncRNA) have been implicated to have critical roles in multiple
      carcinogenesis through a wide range of mechanisms, including modulating the
      stability of proteins. To date, whether the stability of EZH2 protein is
      regulated by lncRNAs remains unexplored. Here we report the discovery of ANCR
      modulating the stability of EZH2, and hence in the invasion and metastasis of
      breast cancer cells. We determined that ANCR potentiated the CDK1-EZH2
      interaction, which then increased the intensity of phosphorylation at Thr-345 and
      Thr-487 sites of EZH2, facilitating EZH2 ubiquitination and hence its
      degradation. Moreover, we also uncover ANCR is an important player in breast
      cancer progression and metastasis mainly through decreasing EZH2 stability. More
      specifically, we initially found that ANCR level was lower in breast cancer
      tissues and breast cancer cell lines, in contrast to their normal counterparts.
      We then demonstrated that knockdown of ANCR induced an EMT program and promoted
      cell migration and invasion in MCF10A (epithelial cells), whereas ectopic
      expression of ANCR repressed breast cancer cells migration and invasion.
      Furthermore, we validated in a nude mouse model that overexpression of ANCR in
      highly malignant and invasive MDA-MB-231 breast cancer cells significantly
      reduced the ability of the cells to form tumors and prevented the lung metastasis
      in vivo. Based on these data, our findings define a new mechanism underlying
      modulation of EZH2 stability by linking ANCR interaction with EZH2 to promote its
      phosphorylation that facilitates EZH2 degradation and suppresses breast cancer
      progression.

PMID- 27716747
TI  - Aflibercept in persistent neovascular AMD: comparison of different treatment
      strategies in switching therapy.

PMID- 27716748
TI  - Aflibercept in persistent neovascular AMD: comparison of different treatment
      strategies in switching therapy.

PMID- 27716746
TI  - Structural and molecular changes in the aging choroid: implications for age
      related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a devastating disease-causing vision
      loss in millions of people around the world. In advanced stages of disease, death
      of photoreceptor cells, retinal pigment epithelial cells, and choroidal
      endothelial cells (CECs) are common. Loss of endothelial cells of the
      choriocapillaris is one of the earliest detectable events in AMD, and, because
      the outer retina relies on the choriocapillaris for metabolic support, this loss
      may be the trigger for progression to more advanced stages. Here we highlight
      evidence for loss of CECs, including changes to vascular density within the
      choriocapillaris, altered abundance of CEC markers, and changes to overall
      thickness of the choroid. Furthermore, we review the key components and functions
      of the choroid, as well as Bruch's membrane, both of which are vital for healthy
      vision. We discuss changes to the structure and molecular composition of these
      tissues, many of which develop with age and may contribute to AMD pathogenesis.
      For example, a crucial event that occurs in the aging choriocapillaris is
      accumulation of the membrane attack complex, which may result in complement
      mediated CEC lysis, and may be a primary cause for AMD-associated
      choriocapillaris degeneration. The actions of elevated monomeric C-reactive
      protein in the choriocapillaris in at-risk individuals may also contribute to the
      inflammatory environment in the choroid and promote disease progression. Finally,
      we discuss the progress that has been made in the development of AMD therapies,
      with a focus on cell replacement.

PMID- 27716749
TI  - Reply to 'Can photoreceptor loss also account for changes in pupil size following
      panretinal photocoagulation?'

PMID- 27716751
TI  - Hormone-replacement therapy: current thinking.
AB  - For several decades, the role of hormone-replacement therapy (HRT) has been
      debated. Early observational data on HRT showed many benefits, including a
      reduction in coronary heart disease (CHD) and mortality. More recently,
      randomized trials, including the Women's Health Initiative (WHI), studying mostly
      women many years after the the onset of menopause, showed no such benefit and,
      indeed, an increased risk of CHD and breast cancer, which led to an abrupt
      decrease in the use of HRT. Subsequent reanalyzes of data from the WHI with age
      stratification, newer randomized and observational data and several meta-analyses
      now consistently show reductions in CHD and mortality when HRT is initiated soon
      after menopause. HRT also significantly decreases the incidence of various
      symptoms of menopause and the risk of osteoporotic fractures, and improves
      quality of life. In younger healthy women (aged 50-60 years), the risk-benefit
      balance is positive for using HRT, with risks considered rare. As no validated
      primary prevention strategies are available for younger women (<60 years of age),
      other than lifestyle management, some consideration might be given to HRT as a
      prevention strategy as treatment can reduce CHD and all-cause mortality. Although
      HRT should be primarily oestrogen-based, no particular HRT regimen can be
      advocated.

PMID- 27716750
TI  - Risk of geographic atrophy in age-related macular degeneration patients treated
      with intravitreal anti-VEGF agents.
AB  - Anti-vascular endothelial growth factor (VEGF) intravitreal agents are the only
      successful treatment for wet age-related macular degeneration (AMD). However,
      there are emerging signals that anti-VEGF treatment can potentially increase
      development of geographic atrophy (GA). Histopathologic, animal, and clinical
      studies support this hypothesis although direct proof of a relationship between
      GA and use of anti-VEGF agents in neovascular AMD is not yet established. This
      review presents current evidence supporting an association between anti-VEGF
      therapy and progression of geographic atrophy. The need of exploring alternative
      methods of treating AMD is indirectly but clearly emphasized.

PMID- 27716752
TI  - Diabetes: Steno-2 - a small study with a big heart.

PMID- 27716754
TI  - [Non alcoholic fatty liver: a growing epidemic].

PMID- 27716755
TI  - [Frequency and in vitro susceptibility antiparasitic of Blastocystis hominis from
      patients admitted to the Hospital Regional Lambayeque, Peru].
AB  - OBJECTIVE: To describe the frequency and antiparasitic in vitro susceptibility of
      Blastocystis hominis in patients admitted to theHospital Regional Lambayeque,
      Peru. MATERIAL AND METHODS: A cross-sectional study was conducted from January to
      August 2015 at 313 patients of all ages. B. hominis detection was performed on
      serial fecal samples by direct microscopic examination and microculture in
      modified Locke solution. The in vitro susceptibility testing against the drug
      metronidazole, nitazoxanide, trimethoprim-sulfamethoxazole and erythromycin was
      performed in 24 strains of B. hominis, which grew up (microculture method) in 10
      double concentrations of each antimicrobial (from 256 ug/ml to 0.5 ug/mL) plus a
      control. RESULTS: 46.3% (145/313) of the sample had B. hominis, also the age
      between 12 to 17 years and 60 years was associated with higher frequency of
      parasites (OR: 2.93 and 2.62). The minimum inhibitory concentration (MIC) 90 of
      metronidazole and nitazoxanide was 3.19 ug/mL and 11.19 ug/ml, respectively,
      whereas the MIC 90 of trimethoprim-sulfamethoxazole and erythromycin were above
      256 ug/mL. CONCLUSIONS: B. hominis occurs in high frequency in patients admitted
      to the Hospital Regional in Lambayeque, proving to be an important problem of
      public health in the region. Also B. hominis isolated from these patients were
      shown to be susceptible in vitro to low concentrations of metronidazole and
      nitazoxanide so they could be chosen for treatment of this parasite.

PMID- 27716756
TI  - [Sphincterotomy followed by papillary large balloon in the management of
      cholecolithiasis. Therapeutic success and safety in a Lima-Peru hospital].
AB  - OBJECTIVE: We present a descriptive analysis of our cases of sphincterotomy
      followed by papillary large balloon dilation in a single session (ES-LBD) in the
      management of difficult to extract calculi, with the objective of assessing rates
      of therapeutic success and complications in local experience. MATERIAL AND
      METHODS: ERCP procedures with ES-LBD performed for choledocholithiasis between
      January 2009 and December 2014 in patients older than 18 years and without
      preexistent sphincterotomy were selected from records of the Gastroenterology
      Service at Cayetano Heredia National Hospital. A descriptive analysis of
      therapeutic success and complications was performed. RESULTS: 73 procedures in 73
      patients were included (65.8% female, 34.2% male). Patient's average age was
      59.4+/-19.8 years. Average diameter of calculi was 14.6+/-3.3mm. Average diameter
      of dilations was 14.6+/-2.27 mm. In 8 cases mechanical lithotripsy was performed.
      Complete calculi extraction was achieved in 56 procedures (76.7%). Complications
      occurred in 4 cases (5.5%). There were no deaths. CONCLUSION: Our figures of
      therapeutic success and complications with ES-LBD for difficult to extract
      calculi are similar to those reported in literature. ES-LBD is an effective and
      safe technique for management of choledocholithiasis.

PMID- 27716753
TI  - Mitochondrial disease and endocrine dysfunction.
AB  - Mitochondria are critical organelles for endocrine health; steroid hormone
      biosynthesis occurs in these organelles and they provide energy in the form of
      ATP for hormone production and trafficking. Mitochondrial diseases are
      multisystem disorders that feature defective oxidative phosphorylation, and are
      characterized by enormous clinical, biochemical and genetic heterogeneity. To
      date, mitochondrial diseases have been found to result from >250 monogenic
      defects encoded across two genomes: the nuclear genome and the ancient circular
      mitochondrial genome located within mitochondria themselves. Endocrine
      dysfunction is often observed in genetic mitochondrial diseases and reflects
      decreased intracellular production or extracellular secretion of hormones.
      Diabetes mellitus is the most frequently described endocrine disturbance in
      patients with inherited mitochondrial diseases, but other endocrine
      manifestations in these patients can include growth hormone deficiency,
      hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease.
      Although mitochondrial endocrine dysfunction frequently occurs in the context of
      multisystem disease, some mitochondrial disorders are characterized by isolated
      endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine
      diseases are anticipated to be revealed by the application of genome-wide next
      generation sequencing approaches in the future. Understanding the mitochondrial
      basis of endocrine disturbance is key to developing innovative therapies for
      patients with mitochondrial diseases.

PMID- 27716757
TI  - [Epidemiological and clinical characteristics of inflammatory bowel disease in a
      tertiary referral hospital in Lima-Peru].
AB  - OBJECTIVE: To identify sociodemographic, clinical, and endoscopic characteristics
      in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: The
      study period was from January 2004 to December 2014. The final diagnosis was
      determined by clinical gastroenterologists experienced in the diagnosis and
      management of IBD, based on internationally accepted diagnostic criteria.
      RESULTS: 105 patients with IBD were studied, 77% with ulcerative colitis (UC) and
      23% with Crohn's disease (CD). The average age of initial diagnosis for UC and CD
      was 53.02 and 57.7 years, respectively. Regarding the gender distribution, the
      male:female ratio was 1.3:1 for UC and 2:1 for CD. Predominant clinical
      manifestations were: diarrhea (76.5%) in CU and lower gastrointestinal bleeding /
      abdominal pain (66.6% for each symptom) in EC. The predominant form of
      presentation was moderate for both CU (49.3%) and EC (62.5%). 47% of patients
      with UC had extensive colitis and 54.2% of patients with CD had Ileocolitis. 6.2%
      of the UC patients underwent surgery, whereas 50% of the CD patients required it.
      CONCLUSIONS: There is a tendency to an increased detection of cases of Crohn's
      disease in our country and in Latin America with respect to previous studies.
      There is a prevalence of moderate forms of presentation for both UC and CD, and
      high percentages of surgery in EC is evident.

PMID- 27716758
TI  - [Gastroprotective effect of honey in Holtzman rats with piroxicam-induced gastric
      ulcer].
AB  - OBJECTIVE: To determine the effect of treatment with honey in piroxicam-induced
      gastric ulcer in Holtzman rats. MATERIALS AND METHODS: 48 eight-week old female
      Holtzman rats, weights between 100 and 200 grams, were divided into 6 treatment
      groups as follow: Group A: water; Group B: piroxicam (30 mg/kg); Group C:
      omeprazole (5 mg/kg) and piroxicam (30 mg/kg); Group D: honey (2.5 g/kg) and
      piroxicam (30 mg/kg); Group E: honey (5 g/kg) and piroxicam (30 mg/kg); Group F:
      honey (7.5 g/kg) and piroxicam (30 mg/kg). Macroscopic studies, using Scion
      Image, and microscopic histological section of gastric mucosa were performed
      after the interventions. RESULTS: The results of the macroscopic studies showed
      statistically significant differences for both doses of honey at 6 g/kg and 7.5
      g/kg when compared to piroxicam (p=0.016 and p=0.001 respectively) and the
      gastroprotective effect was similar when compared to omeprazole (p>0.05).
      Microscopic studies showed statistically significant differences only for dose at
      7.5 g/kg when compared to piroxicam (p=0.0018) and the gastroprotective effect
      was similar to omeprazole (p=1). CONCLUSION: Dose of honey at 7.5 g/kg showed
      gastroprotective effect at microscopic and macroscopic studies when compared to
      omeprazole.

PMID- 27716759
TI  - [Correlation between the presence and intensity of symptoms and the results of
      hydrogen breath tests in the diagnosis of carbohydrate intolerance].
AB  - BACKGROUND: Hydrogen breath tests (HBT) are used to confirm the diagnosis of
      carbohydrate intolerance or small intestinal bacterial overgrowth (SIBO).
      OBJECTIVE: Determine the existence of a correlation between the presence and
      intensity of symptoms experimented by the patient after the ingestion of a
      carbohydrate load and the test result. MATERIALS AND METHODS: This is an
      observational, retrospective and analytic study, in which all patients' files
      from year 2008 to 2014 containing a report of a HBT performed at Hospital San
      Jose TEC de Monterrey were revised. Using a visual analogue scale (VAS), the
      patient reported the intensity of gastrointestinal symptoms during the test.
      Descriptive statistics were obtained, and exclusively for lactose HBTs, Pearson's
      correlation coefficient (r) between maximum hydrogen concentration in breath and
      symptom intensity was calculated. RESULTS: A HBT was performed in 33 patients: 23
      with lactose, 5 with fructose, and 5 with lactulose as substrate. Of these, 10,
      2, and 5 tests were positive, respectively. For lactose HBTs, the symptom with
      most sensitivity was flatulence (80%), which also had the greatest likelihood
      ratio for a positive test (1.73). Diarrhea had the greatest specificity (84.6%).
      A tendency for positivity was observed when patients presented symptoms. A
      moderately positive correlation between hydrogen ppm and symptom intensity was
      found (r=0.427, p=0.023). CONCLUSIONS: A correlation between symptom intensity
      and test positivity was found in patients with lactose intolerance. The presence
      of flatulence after lactose loading may be indicative of a positive test.

PMID- 27716761
TI  - [A current perspective of natural orifices transluminal endoscopic surgery
      (NOTES)].
AB  - Natural orifice transluminal endoscopic surgery (NOTES) represents an alternative
      in surgical approach, combined with the progress and experience gained from
      conventional and endoscopic surgery. Bibliographic research in PubMed, Medline
      database from 2000 to 2015 and analysis of the literature reviews found. NOTES
      provides vision and natural orifice approach, it has optimized operating times as
      well as reduced complications and better cosmetic results. Small series of
      patients have been reported, but there is not a valid clinical multicenter study
      by evidence-based medicine. NOTES can help to improve the standard operations,
      complemented with laparoscopic surgery rather than replace it and thus develop
      tools for the resolution of various diseases that require surgical treatment.
      This option in current surgery is safe and presents satisfactory results in the
      reported cases. The development of this new approach of performing surgical
      procedures requires further study and development of new technology in order to
      increase the accessibility of these procedures and represent in a practical and
      sustained way, a better option to approach surgical pathology.

PMID- 27716760
TI  - Ex vivo and simulator models teaching therapeutic ERCP and EUS: description of
      SOBED's first course.
AB  - Teaching models in endoscopy are important tools to minimize risks derived from
      endoscopic procedures, taking into account that therapeutic endoscopy, also known
      as surgical endoscopy, has greatly developed during the last decade. This results
      from the fact that minimally invasive procedures present relevant contributions
      and promote more comfort to patients. In this context, ex vivo teaching models
      and virtual simulators are important tools to the safe acquisition of abilities.
      In this article, the Brazilian Society of Digestive Endoscopy presents and
      describes its first course of therapeutic ERCP and EUS in models of laboratory
      teaching.

PMID- 27716762
TI  - [Spontaneous liver rupture in a patient with choledocholithiasis resolved by
      ERCP].
AB  - We present the case of a 34 years old female patient who presents with abdominal
      pain and elevated total and direct bilirrubins, so she underwent ERCP Reporting:
      a) successful sphincterotomy without complications, b) choledocholithias is
      endoscopically resolved, c) secondary cholangitis. She developed significant
      abdominal pain at 72 h, with hypovolemic shock and peritoneal irritation. She was
      taken to the surgery, finding a grade III liver laceration. This one was resolved
      with liver raffia and packing, during the same operative time cholecystectomy was
      performed. A second look was performed at 24 h, achieving adequate control of
      bleeding after placing hemostatic (Nexstat(r)). The patient developed a
      subdiaphragmatic abscess which needed drainage by another laparotomy. After which
      the patient had a satisfactory evolution, so she was discharged.

PMID- 27716763
TI  - Type 1 autoimmune pancreatitis: case scenario and review of the disease.
AB  - Autoimmune pancreatitis (AIP) is an uncommon disease that represents a diagnostic
      challenge unless it is considered as a cause of acute pancreatitis, pancreatic
      exocrine insufficiency and a pancreatic mass. This entity is under diagnosed and
      successful medical therapy is available. In this paper, we will describe a case
      of a 59 year-old, Hispanic woman diagnosed with autoimmune pancreatitis, a
      disease previously believed to affect typically older men. We will review the
      definition, types, clinical manifestations, radiological features, serology,
      histopathological findings, treatment strategies and diagnostic criteria of
      autoimmune pancreatitis.

PMID- 27716764
TI  - [Use of corticosteroids in esophagitis caustic ingestion. Report of two cases].
AB  - Exposure to potentially toxic substances represents 0.3% of annual visits to a
      pediatric emergency department, being a situation likely to be prevented and that
      generates a non-negligible morbidity and mortality. The most common route of
      exposure is the oral and drugs are the products most frequently involved.
      Esophagitis caustic ingestion of corrosive substances in childhood is now a
      public health problem in developing countries. Clinical manifestations vary from
      no injuries serious commitment to high risk of death observed more frequently in
      patients between one and three years old. In addition to drilling, the most
      severe complication of esophagitis is caustic stricture formation, which occurs
      at a frequency of 5% to 47% in severe cases. The role of systemic corticosteroids
      in preventing caustic esophageal stenosis is still considered controversial,
      despite the many published reports showing your benefit. We report two cases of
      pediatric patients with caustic esophagitis IIB Zargar who received systemic
      corticosteroids with favorable evolution.

PMID- 27716765
TI  - [Venous tromboembolism in a patient with Crohn disease with ileal stenosis].
AB  - Inflammatory bowel disease is associated with extraintestinal manifestations.
      Among these manifestations is the venous tromboembolism which presents a risk
      three times more than that presented in general population. We report the case of
      a 61-year-old male with a history of abdominal pain, chronic diarrhea and fever,
      with leukocytosis, and fecal samples containing leukocytes, partial ileal
      stenosis with multiple ulcers in the enteroscopy, with histologic findings
      compatible with Crohn's disease. The patient has a good outcome with prednisone
      and maintenence azathioprine, presenting at the fifth month deep venous
      thrombosis of both lower extremities that resolvewith anticoagulation treatment.

PMID- 27716766
TI  - [Hydatid cysts in pancreas: laparoscopic approach].
AB  - : Hydatid disease is a parasitic infestation caused by Echinococcus and is
      endemic in many areas of the world. Hydatid cysts are commonly located in the
      liver and lung. Pancreas affection is very rare even in endemic areas. CASE
      REPORT: 36-year-old female with the suspicion of hydatid disease of the pancreas
      5 years before her admission. The patient gave history of epigastric pain and
      weight lose. CT scan and MRI showed a cystic lesion of the tail of the pancreas
      and the diagnosis of hydatid disease was confirmed with ELIZA and Western Blot.
      The patient underwent a laparoscopic distal spleno pancreatectomy. The recovery
      was uneventful. CONCLUSION: Hydatid disease must be considered in the
      differential diagnosis of the cystic lesions of the pancreas, especially in
      patients who come from endemic areas.

PMID- 27716767
TI  - [Carcinoid tumor of gastrointestinal tract: about two clinical cases].
AB  - Carcinoid tumors belong to the families of neuroendocrine tumors. The major sites
      are the gastrointestinal tract 65% and lungs 25%. The small intestine,
      specifically the ileum, is the most common. These tumors although rare, are more
      common in tumors of neuroendocrine origin gastro-entero-pancreatic. In both cases
      we observe the different clinical presentations that may have carcinoid tumor; in
      case 1 ulceration of the tumor mass causing the elimination of melena, and severe
      diarrhea caused by neuroendocrine secretion. Case 2 typical course, totally
      asymptomatic incidental finding.

PMID- 27716768
TI  - [Item validation of a quality of life questionnaire for patients with gastric
      cancer].

PMID- 27716769
TI  - [GlobalSurg 1's participation from Peru and new challenges for GlobalSurg 2:
      epidemiology of surgical site infection].

PMID- 27716770
TI  - [Experimental studies, SciELO-Peru 2006 - 2015: ethics].

PMID- 27716771
TI  - Identification and Tumour-Binding Properties of a Peptide with High Affinity to
      the Disialoganglioside GD2.
AB  - Neuroectodermal tumours are characterized by aberrant processing of
      disialogangliosides concomitant with high expression of GD2 or GD3 on cell
      surfaces. Antibodies targeting GD2 are already in clinical use for therapy of
      neuroblastoma, a solid tumour of early childhood. Here, we set out to identify
      peptides with high affinity to human disialoganglioside GD2. To this end, we
      performed a combined in vivo and in vitro screen using a recombinant phage
      displayed peptide library. We isolated a phage displaying the peptide sequence
      WHWRLPS that specifically binds to the human disialoganglioside GD2. Binding
      specificity was confirmed by mutational scanning and by comparative analyses
      using structurally related disialogangliosides. In vivo, significant enrichment
      of phage binding to xenografts of human neuroblastoma cells in mice was observed.
      Tumour-specific phage accumulation could be blocked by intravenous coinjection of
      the corresponding peptide. Comparative pharmacokinetic analyses revealed higher
      specific accumulation of 68Ga-labelled GD2-binding peptide compared to 111In
      labelled peptide in xenografts of human neuroblastoma. In contrast to 124I-MIBG,
      which is currently evaluated as a neuroblastoma marker in PET/CT, 68Ga-labelled
      GD2-specific peptide spared the thyroid but was enriched in the kidneys, which
      could be partially blocked by infusion of amino acids.In summary, we here report
      on a novel tumour-homing peptide that specifically binds to the
      disialoganglioside GD2, accumulates in xenografts of neuroblastoma cells in mice
      and bears the potential for tumour detection using PET/CT. Thus, this peptide may
      serve as a new scaffold for diagnosing GD2-positive tumours of neuroectodermal
      origin.

PMID- 27716772
TI  - The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by
      Reducing Smooth Muscle [Ca2+]i.
AB  - RATIONALE: Nebivolol is known to have beta-1 blocker activity, but it was also
      suggested that it elicits relaxation of the peripheral arteries in part via
      release of nitric oxide (NO). However, the effect of nebivolol on the vasomotor
      tone of cerebral arteries is still unclear. OBJECTIVE: To assess the effects of
      nebivolol on the diameter of isolated rat basilar arteries (BA) in control, in
      the presence of inhibitors of vasomotor signaling pathways of know action and
      hemolysed blood. METHODS AND RESULTS: Vasomotor responses were measured by
      videomicroscopy and the intracellular Ca2+ by the Fura-2 AM ratiometric method.
      Under control conditions, nebivolol elicited a substantial dilation of the BA
      (from 216+/-22 to 394+/-20 MUm; p<0.05) in a concentration-dependent manner (10-7
      to 10-4 M). The dilatation was significantly reduced by endothelium denudation or
      by L-NAME (inhibitor of NO synthase) or by SQ22536 (adenylyl cyclase blocker).
      Dilatation of BA was also affected by beta-2 receptor blockade with butoxamine,
      but not by the guanylate cyclase blocker ODQ. Interestingly, beta-1 blockade by
      atenolol inhibited nebivolol-induced dilation. Also, the BKCa channel blocker
      iberiotoxin and KCa channel inhibitor TEA significantly reduced nebivolol-induced
      dilation. Nebivolol significantly reduced smooth muscle Ca2+ level, which
      correlated with the increases in diameters and moreover it reversed the hemolysed
      blood-induced constriction of BA. CONCLUSIONS: Nebivolol seems to have an
      important dilator effect in cerebral arteries, which is mediated via several
      vasomotor mechanisms, converging on the reduction of smooth muscle Ca2+ levels.
      As such, nebivolol may be effective to improve cerebral circulation in various
      diseased conditions, such as hemorrhage.

PMID- 27716773
TI  - Enhanced Mitogenic Activity of Recombinant Human Vascular Endothelial Growth
      Factor VEGF121 Expressed in E. coli Origami B (DE3) with Molecular Chaperones.
AB  - We describe the production of a highly-active mutant VEGF variant, alpha2-PI1-8
      VEGF121, which contains a substrate sequence for factor XIIIa at the
      aminoterminus designed for incorporation into a fibrin gel. The alpha2-PI1-8
      VEGF121 gene was synthesized, cloned into a pET-32a(+) vector and expressed in
      Escherichia coli Origami B (DE3) host cells. To increase the protein folding and
      the solubility, the resulting thioredoxin-alpha2-PI1-8-VEGF121 fusion protein was
      co-expressed with recombinant molecular chaperones GroES/EL encoded by
      independent plasmid pGro7. The fusion protein was purified from the soluble
      fraction of cytoplasmic proteins using affinity chromatography. After cleavage of
      the thioredoxin fusion part with thrombin, the target protein was purified by a
      second round of affinity chromatography. The yield of purified alpha2-PI1-8
      VEGF121 was 1.4 mg per liter of the cell culture. The alpha2-PI1-8-VEGF121
      expressed in this work increased the proliferation of endothelial cells 3.9-8.7
      times in comparison with commercially-available recombinant VEGF121. This very
      high mitogenic activity may be caused by co-expression of the growth factor with
      molecular chaperones not previously used in VEGF production. At the same time,
      alpha2-PI1-8-VEGF121 did not elicit considerable inflammatory activation of human
      endothelial HUVEC cells and human monocyte-like THP-1 cells.

PMID- 27716774
TI  - Ontogeny of Unstable Chromosomes Generated by Telomere Error in Budding Yeast.
AB  - DNA replication errors at certain sites in the genome initiate chromosome
      instability that ultimately leads to stable genomic rearrangements. Where
      instability begins is often unclear. And, early instability may form unstable
      chromosome intermediates whose transient nature also hinders mechanistic
      understanding. We report here a budding yeast model that reveals the genetic
      ontogeny of genome rearrangements, from initial replication error to unstable
      chromosome formation to their resolution. Remarkably, the initial error often
      arises in or near the telomere, and frequently forms unstable chromosomes. Early
      unstable chromosomes may then resolve to an internal "collection site" where a
      dicentric forms and resolves to an isochromosome (other outcomes are possible at
      each step). The initial telomere-proximal unstable chromosome is increased in
      mutants in telomerase subunits, Tel1, and even Rad9, with no known telomere
      specific function. Defects in Tel1 and in Rrm3, a checkpoint protein kinase with
      a role in telomere maintenance and a DNA helicase, respectively, synergize
      dramatically to generate unstable chromosomes, further illustrating the
      consequence of replication error in the telomere. Collectively, our results
      suggest telomeric replication errors may be a common cause of seemingly unrelated
      genomic rearrangements located hundreds of kilobases away.

PMID- 27716775
TI  - Mechano-chemical Interactions in Cardiac Sarcomere Contraction: A Computational
      Modeling Study.
AB  - We developed a model of cardiac sarcomere contraction to study the calcium
      tension relationship in cardiac muscle. Calcium mediates cardiac contraction
      through its interactions with troponin (Tn) and subsequently tropomyosin
      molecules. Experimental studies have shown that a slight increase in
      intracellular calcium concentration leads to a rapid increase in sarcomeric
      tension. Though it is widely accepted that the rapid increase is not possible
      without the concept of cooperativity, the mechanism is debated. We use the
      hypothesis that there exists a base level of cooperativity intrinsic to the thin
      filament that is boosted by mechanical tension, i.e. a high level of mechanical
      tension in the thin filament impedes the unbinding of calcium from Tn. To test
      these hypotheses, we developed a computational model in which a set of three
      parameters and inputs of calcium concentration and sarcomere length result in
      output tension. Tension as simulated appeared in good agreement with
      experimentally measured tension. Our results support the hypothesis that high
      tension in the thin filament impedes Tn deactivation by increasing the energy
      required to detach calcium from the Tn. Given this hypothesis, the model
      predicted that the areas with highest tension, i.e. closest to the Z-disk end of
      the single overlap region, show the largest concentration of active Tn's.

PMID- 27716776
TI  - A Dynamic Model of Post-Traumatic Stress Disorder for Military Personnel and
      Veterans.
AB  - Post-traumatic stress disorder (PTSD) stands out as a major mental illness;
      however, little is known about effective policies for mitigating the problem. The
      importance and complexity of PTSD raise critical questions: What are the trends
      in the population of PTSD patients among military personnel and veterans in the
      postwar era? What policies can help mitigate PTSD? To address these questions, we
      developed a system dynamics simulation model of the population of military
      personnel and veterans affected by PTSD. The model includes both military
      personnel and veterans in a "system of systems." This is a novel aspect of our
      model, since many policies implemented at the military level will potentially
      influence (and may have side effects on) veterans and the Department of Veterans
      Affairs. The model is first validated by replicating the historical data on PTSD
      prevalence among military personnel and veterans from 2000 to 2014 (datasets from
      the Department of Defense, the Institute of Medicine, the Department of Veterans
      Affairs, and other sources). The model is then used for health policy analysis.
      Our results show that, in an optimistic scenario based on the status quo of
      deployment to intense/combat zones, estimated PTSD prevalence among veterans will
      be at least 10% during the next decade. The model postulates that during wars,
      resiliency-related policies are the most effective for decreasing PTSD. In a
      postwar period, current health policy interventions (e.g., screening and
      treatment) have marginal effects on mitigating the problem of PTSD, that is, the
      current screening and treatment policies must be revolutionized to have any
      noticeable effect. Furthermore, the simulation results show that it takes a long
      time, on the order of 40 years, to mitigate the psychiatric consequences of a
      war. Policy and financial implications of the findings are discussed.

PMID- 27716778
TI  - Correction: Surveillance-Activated Defenses Block the ROS-Induced Mitochondrial
      Unfolded Protein Response.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1003346.].

PMID- 27716777
TI  - Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation.
AB  - Thioredoxin (Trx) is an oxidoreductase with important physiological function.
      Imbalances in the NADPH/thioredoxin reductase/thioredoxin system are associated
      with a number of pathologies, particularly cancer, and a number of clinical
      trials for thioredoxin and thioredoxin reductase inhibitors have been carried out
      or are underway. Due to the emerging role and importance of oxidoreductases for
      haemostasis and the current interest in developing inhibitors for clinical use,
      we thought it pertinent to assess whether inhibition of the NADPH/thioredoxin
      reductase/thioredoxin system affects platelet function and thrombosis. We used
      small molecule inhibitors of Trx (PMX 464 and PX-12) to determine whether Trx
      activity influences platelet function, as well as an unbiased proteomics approach
      to identify potential Trx substrates on the surface of platelets that might
      contribute to platelet reactivity and function. Using LC-MS/MS we found that PMX
      464 and PX-12 affected the oxidation state of thiols in a number of cell surface
      proteins. Key surface receptors for platelet adhesion and activation were
      affected, including the collagen receptor GPVI and the von Willebrand factor
      receptor, GPIb. To experimentally validate these findings we assessed platelet
      function in the presence of PMX 464, PX-12, and rutin (a selective inhibitor of
      the related protein disulphide isomerase). In agreement with the proteomics data,
      small molecule inhibitors of thioredoxin selectively inhibited GPVI-mediated
      platelet activation, and attenuated ristocetin-induced GPIb-vWF-mediated platelet
      agglutination, thus validating the findings of the proteomics study. These data
      reveal a novel role for thioredoxin in regulating platelet reactivity via
      proteins required for early platelet responses at sites of vessel injury (GPVI
      and GPIb). This work also highlights a potential opportunity for repurposing of
      PMX 464 and PX-12 as antiplatelet agents.

PMID- 27716779
TI  - Antibiotic Treatment and Length of Hospital Stay in Relation to Delivery Mode and
      Prematurity.
AB  - AIM: To investigate how 1) maternal delivery mode and 2) prematurity in infants
      are associated to antibiotic treatment and length of hospital stay. METHODS:
      Women having given birth and infants 0-12 months discharged from hospital between
      July 2005 and November 2011 were identified from the Swedish National Patient
      Register. Medical records were reviewed for 203 women and 527 infants. The risk
      ratio (RR) between antibiotic treatment and 1) delivery mode in women; 2)
      prematurity in infants was calculated. Length of stay and days of antibiotic
      therapy were compared by Wilcoxon rank-sum test. RESULTS: Women: There was an
      association between emergency caesarean section (CS) and antibiotic treatment (RR
      5.0 95% confidence interval (CI) 2.2-11.5), but not for elective CS. Length of
      stay was longer for CS (emergency and elective) compared to vaginal delivery
      (p<0.01). Infants: RR for antibiotic treatment in preterm compared to term
      infants was 1.4 (95% CI 1.0-1.9). Length of stay (p<0.01), but not days of
      therapy (p = 0.17), was higher in preterm compared to term infants. CONCLUSION:
      We found that emergency CS increased the probability of maternal antibiotic
      treatment during hospitalisation, but no difference was found between term and
      preterm infants. The results are well aligned with current guidelines and may be
      considered in future studies on the effects of antibiotics.

PMID- 27716780
TI  - Complex Particulate Biomaterials as Immunostimulant-Delivery Platforms.
AB  - The control of infectious diseases is a major current challenge in intensive
      aquaculture. Most commercial vaccines are based on live attenuated or inactivated
      pathogens that are usually combined with adjuvants, oil emulsions being as the
      most widely used for vaccination in aquaculture. Although effective, the use of
      these oil emulsions is plagued with important side effects. Thus, the development
      of alternative safer and cost-effective immunostimulants and adjuvants is highly
      desirable. Here we have explored the capacity of inclusion bodies produced in
      bacteria to immunostimulate and protect fish against bacterial infections.
      Bacterial inclusion bodies are highly stable, non-toxic protein-based
      biomaterials produced through fully scalable and low-cost bio-production
      processes. The present study shows that the composition and structured
      organization of inclusion body components (protein, lipopolysaccharide,
      peptidoglycan, DNA and RNA) make these protein biomaterials excellent
      immunomodulators able to generically protect fish against otherwise lethal
      bacterial challenges. The results obtained in this work provide evidence that
      their inherent nature makes bacterial inclusion bodies exceptionally attractive
      as immunostimulants and this opens the door to the future exploration of this
      biomaterial as an alternative adjuvant for vaccination purposes in veterinary.

PMID- 27716782
TI  - Visualization of Anatomic Variation of the Anterior Septal Vein on Susceptibility
      Weighted Imaging.
AB  - BACKGROUND AND PURPOSE: Understanding the anatomy of the anterior septal vein
      (ASV) is critical for minimally invasive procedures to the third ventricle and
      for assessing lesion size and venous drainage in the anterior cranial fossa.
      Accordingly, this study evaluated topographic anatomy and anatomic variation of
      the ASV using susceptibility-weighted imaging (SWI). METHODS: Sixty volunteers
      were examined using a 3.0T MR system. The diameter of the ASV and distance
      between bilateral septal points were measured. ASVs were divided into types 1
      (only drains frontal lobe) and 2 (drains both frontal lobe and head of the
      caudate nucleus). We evaluated the ASV-internal cerebral vein (ICV) junction
      based on its positional relationship with the appearance of a venous angle or a
      false venous angle and the foramen of Monro. Fused SW and T1-weighted images were
      used to observe positional relationships between the course of the ASV and the
      surrounding brain structures. RESULTS: The ASV and its small tributaries were
      clearly visualized in 120 hemispheres (100%). The average diameter of ASVs was
      1.05+/-0.17 mm (range 0.9-1.6 mm). The average distance between bilateral septal
      points was 2.23+/-1.03 mm (range 1.3-6.6 mm). The ASV types 1 and 2 were in 77
      (64.2%) and 43 (35.8%) hemispheres, respectively. In 83 (69.2%) hemispheres, the
      ASV-ICV junction was situated at the venous angle and the posterior margin of the
      foramen of Monro. In 37 (30.8%) hemispheres, the ASV-ICV junction was situated
      beyond the posterior margin of the foramen of Monro. The average distance between
      the posteriorly located ASV-ICV junction and the posterior margin of the foramen
      of Monro was 6.41+/-3.95 mm (range 2.4-15.9 mm). CONCLUSION: Using SWI, the
      topographic anatomy and anatomic variation of the ASV were clearly demonstrated.
      Preoperative assessment of anatomic variation of the ASV may be advantageous for
      minimally invasive neurosurgical procedures.

PMID- 27716781
TI  - Cross-Species Analysis of Gene Expression and Function in Prefrontal Cortex,
      Hippocampus and Striatum.
AB  - BACKGROUND: Mouse has been extensively used as a tool for investigating the onset
      and development of human neurological disorders. As a first step to construct a
      transgenic mouse model of human brain lesions, it is of fundamental importance to
      clarify the similarity and divergence of genetic background between non-diseased
      human and mouse brain tissues. METHODS: We systematically compared, based on
      large scale integrated microarray data, the transcriptomes of three anatomically
      distinct brain regions; prefrontal cortex (PFC), hippocampus (HIP) and striatum
      (STR), across human and mouse. The widely used DAVID web server was used to
      decipher the biological functions of the highly expressed genes that were
      identified using a previously reported approach. Venn analysis was used to depict
      the overlapping ratios of the notably enriched biological process (BP) terms (one
      tailed Fisher's exact test and Benjamini correction; adjusted p < 0.01) between
      two brain tissues. GOSemSim, an R package, was selected to perform GO semantic
      similarity analysis. Next, we adjusted signal intensities of orthologous genes by
      the total signals in all samples within species, and used one minus Pearson's
      correlation coefficient to assess the expression distance. Hierarchical
      clustering and principal component analysis (PCA) were selected for expression
      pattern analysis. Lineage specific expressed orthologous genes were identified by
      comparison of the most extreme sub-datasets across species and further verified
      using reverse transcription PCR (RT-PCR) and quantitative real-time PCR (qRT
      PCR). RESULTS: We found that the number of the significantly enriched BP terms of
      the highly expressed genes in human brain regions is larger than that in mouse
      corresponding brain regions. The mainly involved BP terms in human brain tissues
      associated with protein-membrane targeting and selenium metabolism are species
      specific. The overlapping ratios of all the significantly enriched BP terms
      between any two brain tissues across species are lower than that within species,
      but the pairwise semantic similarities are very high between any two brain
      tissues from either human or mouse. Hierarchical clustering analysis shows the
      biological functions of the highly expressed genes in brain tissues are more
      consistent within species than interspecies; whereas it shows the expression
      patterns of orthologous genes are evidently conserved between human and mouse
      equivalent brain tissues. In addition, we identified four orthologous genes
      (COX5B, WIF1, SLC4A10 and PLA2G7) that are species-specific, which have been
      widely studied and confirmed to be closely linked with neuro- physiological and
      pathological functions. CONCLUSION: Our study highlights the similarities and
      divergences in gene function and expression between human and mouse corresponding
      brain regions, including PFC, HIP and STR.

PMID- 27716783
TI  - Functional Properties of Mouse Chitotriosidase Expressed in the Periplasmic Space
      of Escherichia coli.
AB  - Chitotriosidase (Chit1) is an enzyme associated with various diseases, including
      Gaucher disease, chronic obstructive pulmonary disease, Alzheimer disease and
      cystic fibrosis. In this study, we first expressed mouse mature Chit1 fused with
      V5 and (His)6 tags at the C-terminus (Chit1-V5-His) in the cytoplasm of
      Escherichia coli and found that most of the expressed protein was insoluble. In
      contrast, Chit1 tagged with Protein A at the N-terminus and V5-His at the C
      terminus, was expressed in the periplasmic space of E. coli as a soluble protein
      and successfully purified. We evaluated the chitinolytic properties of the
      recombinant enzyme using 4-nitrophenyl N,N'-diacetyl-beta-D-chitobioside [4NP
      chitobioside, 4NP-(GlcNAc)2] and found that its activity was comparable to CHO
      cells-expressed Chit1-V5-His. Optimal conditions for the E. coli-produced Chit1
      were pH ~5.0 at 50 degrees C. Chit1 was stable after 1 h incubation at pH
      5.0~11.0 on ice and its chitinolytic activity was lost at pH 2.0, although the
      affinity to chitin remained unchanged. Chit1 efficiently cleaved crystalline and
      colloidal chitin substrates as well as oligomers of N-acetyl-D-glucosamine
      (GlcNAc) releasing primarily (GlcNAc)2 fragments at pH 5.0. On the other hand,
      (GlcNAc)3 was relatively resistant to digestion by Chit1. The degradation of 4NP
      (GlcNAc)2 and (GlcNAc)3 was less evident at pH 7.0~8.0, while (GlcNAc)2
      production from colloidal chitin and (GlcNAc)6 at these pH conditions remained
      strong at the neutral conditions. Our results indicate that Chit1 degrades chitin
      substrates under physiological conditions and suggest its important
      pathophysiological roles in vivo.

PMID- 27716784
TI  - The Mechanism of Proinflammatory HDL Generation in Sickle Cell Disease Is Linked
      to Cell-Free Hemoglobin via Haptoglobin.
AB  - In sickle cell disease (SCD), the inflammatory properties of high-density
      lipoprotein (HDL) can be changed by cell-free hemoglobin (Hb), which is released
      into the blood during hemolysis. Hb in the plasma of SCD patients or mice can
      bind with HDL specifically inducing an inflammatory reaction. In our study, we
      found increased amounts of inflammatory factor proteins in the chronic oxidative
      state of SCD with higher levels of Hb, haptoglobin (Hp) and hemopexin (Hx) in the
      apolipoprotein A-I (ApoA-1) particles of HDL and the role of HDL is changed from
      being anti-inflammatory to proinflammatory. Our results also suggest Hp and Hx,
      the scavengers of Hb in HDL, are positively associated with inflammatory levels
      in SCD patients. HDL retained its inflammatory inhibition role in Hp-/- mice,
      with less Hb accumulation. Hx may further prevent inflammatory reaction because
      its level will be even higher when lack of Hx. We therefore demonstrated that Hp
      is indispensable during the process whereby Hb associates with HDL and plays a
      clear proinflammatory role. Therefore, it is essential to break the binding
      between Hb and Hp for treatment. The dissociation of Hb/Hp/Hx complexes may also
      play an important role in the study of other inflammatory angiogenesis-related
      diseases.

PMID- 27716786
TI  - Overlapping Leaves Covering Flowers in the Alpine Species Eriophyton wallichii
      (Lamiaceae): Key Driving Factors and Their Potential Impact on Pollination.
AB  - Extrafloral structures are supposed to have evolved to protect flowers from harsh
      physical environments but might have effects on pollination. Overlapping leaves
      cover flowers in Eriophyton wallichii, an alpine perennial endemic to the
      Himalaya-Hengduan Mountains. In previous study, it has showed that these
      extrafloral leaves can protect interior flowers from temperature fluctuations
      caused by drastic solar radiation fluctuations, but these leaves may also protect
      interior flowers from rain wash and UVB damage, and we do not know which one is
      the main function. In this study, we investigated whether rain and UVB protection
      are the main functions of overlapping leaves covering flowers and their potential
      impact on pollination. We first measured the intensities of UVB radiation in open
      air, beneath leaves and corollas, and then examined pollen susceptibility to
      different intensities of UVB and rain in the laboratory to estimate whether
      corollas per se protect interior pollen from UVB and rain damage. We also carried
      out pollination treatments and observed pollinator visitation of flowers with and
      without leaves in the field to assess whether the overlapping leaves covering
      flowers impair pollinator attraction. Our results showed that (1) water and
      strong UVB significantly decreased pollen germinability, but corollas per se
      could protect pollen from UVB and rain damage; (2) no autonomous self-pollination
      and apomixis occurred, and pollinators were essential for the reproduction of E.
      wallichii; however, flower coverage by overlapping leaves did not limit
      pollination. We suggested that rain and UVB protection was not the main function
      of overlapping leaves covered flowers, given that this protection can be provided
      by corollas per se. Alternatively, this extrafloral structure in E. wallichii may
      have evolved in response to extreme high temperatures associated with the strong
      solar radiation fluctuations. This indicates that, even in alpine plants, extreme
      high temperature may affect the evolution of plant extrafloral structures.

PMID- 27716785
TI  - Using Rich Data on Comorbidities in Case-Control Study Design with Electronic
      Health Record Data Improves Control of Confounding in the Detection of Adverse
      Drug Reactions.
AB  - Recent research has suggested that the case-control study design, unlike the self
      controlled study design, performs poorly in controlling confounding in the
      detection of adverse drug reactions (ADRs) from administrative claims and
      electronic health record (EHR) data, resulting in biased estimates of the causal
      effects of drugs on health outcomes of interest (HOI) and inaccurate confidence
      intervals. Here we show that using rich data on comorbidities and automatic
      variable selection strategies for selecting confounders can better control
      confounding within a case-control study design and provide a more solid basis for
      inference regarding the causal effects of drugs on HOIs. Four HOIs are examined:
      acute kidney injury, acute liver injury, acute myocardial infarction and
      gastrointestinal ulcer hospitalization. For each of these HOIs we use a
      previously published reference set of positive and negative control drugs to
      evaluate the performance of our methods. Our methods have AUCs that are often
      substantially higher than the AUCs of a baseline method that only uses
      demographic characteristics for confounding control. Our methods also give
      confidence intervals for causal effect parameters that cover the expected no
      effect value substantially more often than this baseline method. The case-control
      study design, unlike the self-controlled study design, can be used in the fairly
      typical setting of EHR databases without longitudinal information on patients.
      With our variable selection method, these databases can be more effectively used
      for the detection of ADRs.

PMID- 27716787
TI  - Fluoxetine Increases the Expression of miR-572 and miR-663a in Human
      Neuroblastoma Cell Lines.
AB  - Evidence suggests neuroprotective effects of fluoxetine, a selective serotonin
      reuptake inhibitor (SSRI), on the developed neurons in the adult brain. In
      contrast, the drug may be deleterious to immature or undifferentiated neural
      cells, although the mechanism is unclear. Recent investigations have suggested
      that microRNAs (miRNA) may be critical for effectiveness of psychotropic drugs
      including SSRI. We investigated whether fluoxetine could modulate expressions of
      neurologically relevant miRNAs in two neuroblastoma SK-N-SH and SH-SY5Y cell
      lines. Initial screening results revealed that three (miR-489, miR-572 and miR
      663a) and four (miR-320a, miR-489, miR-572 and miR-663a) miRNAs were up-regulated
      in SK-N-SH cells and SH-SY5Y cells, respectively, after 24 hours treatment of
      fluoxetine (1-25 MUM). Cell viability was reduced according to the dose of
      fluoxetine. The upregulation of miR-572 and miR-663a was consistent in both the
      SH-SY5Y and SK-N-SH cells, confirmed by a larger scale culture condition. Our
      data is the first in vitro evidence that fluoxetine could increase the expression
      of miRNAs in undifferentiated neural cells, and that putative target genes of
      those miRNAs have been shown to be involved in fundamental neurodevelopmental
      processes.

PMID- 27716788
TI  - Vimar Is a Novel Regulator of Mitochondrial Fission through Miro.
AB  - As fundamental processes in mitochondrial dynamics, mitochondrial fusion, fission
      and transport are regulated by several core components, including Miro. As an
      atypical Rho-like small GTPase with high molecular mass, the exchange of GDP/GTP
      in Miro may require assistance from a guanine nucleotide exchange factor (GEF).
      However, the GEF for Miro has not been identified. While studying mitochondrial
      morphology in Drosophila, we incidentally observed that the loss of vimar, a gene
      encoding an atypical GEF, enhanced mitochondrial fission under normal
      physiological conditions. Because Vimar could co-immunoprecipitate with Miro in
      vitro, we speculated that Vimar might be the GEF of Miro. In support of this
      hypothesis, a loss-of-function (LOF) vimar mutant rescued mitochondrial
      enlargement induced by a gain-of-function (GOF) Miro transgene; whereas a GOF
      vimar transgene enhanced Miro function. In addition, vimar lost its effect under
      the expression of a constitutively GTP-bound or GDP-bound Miro mutant background.
      These results indicate a genetic dependence of vimar on Miro. Moreover, we found
      that mitochondrial fission played a functional role in high-calcium induced
      necrosis, and a LOF vimar mutant rescued the mitochondrial fission defect and
      cell death. This result can also be explained by vimar's function through Miro,
      because Miro's effect on mitochondrial morphology is altered upon binding with
      calcium. In addition, a PINK1 mutant, which induced mitochondrial enlargement and
      had been considered as a Drosophila model of Parkinson's disease (PD), caused fly
      muscle defects, and the loss of vimar could rescue these defects. Furthermore, we
      found that the mammalian homolog of Vimar, RAP1GDS1, played a similar role in
      regulating mitochondrial morphology, suggesting a functional conservation of this
      GEF member. The Miro/Vimar complex may be a promising drug target for diseases in
      which mitochondrial fission and fusion are dysfunctional.

PMID- 27716789
TI  - Risk of Adverse Obstetric and Neonatal Outcomes by Maternal Age: Quantifying
      Individual and Population Level Risk Using Routine UK Maternity Data.
AB  - OBJECTIVE: The objective of this study was to investigate whether moderately
      increased maternal age is associated with obstetric and neonatal outcome in a
      contemporary population, and to consider the possible role of co-morbidities in
      explaining any increased risk. STUDY DESIGN: Secondary analysis of routinely
      collected data from a large maternity unit in London, UK. Data were available on
      51,225 singleton deliveries (>=22 weeks) occurring to women aged >=20 between
      2004 and 2012. Modified Poisson regression was used to estimate risk ratios for
      the association between maternal age and obstetric and neonatal outcome (delivery
      type, postpartum haemorrhage, stillbirth, low birthweight, preterm birth, small
      for gestational age, neonatal unit admission), using the reference group 20-24
      years. Population attributable fractions were calculated to quantify the
      population impact. RESULTS: We found an association between increasing maternal
      age and major postpartum haemorrhage (>=1000ml blood loss) (RR 1.36 95% CI 1.18
      1.57 for age 25-29 rising to 2.41 95% CI 2.02-2.88 for age >=40). Similar trends
      were observed for caesarean delivery, most notably for elective caesareans (RR
      1.64 95% CI 1.36-1.96 for age 25-29 rising to 4.94 95% CI 4.09-5.96 for age
      >=40). There was evidence that parity modified this association, with a higher
      prevalence of elective caesarean delivery in older nulliparous women. Women aged
      >=35 were at increased risk of low birthweight and preterm birth. We found no
      evidence that the risk of stillbirth, small for gestational age, or neonatal unit
      admission differed by maternal age. CONCLUSIONS: Our results suggest a gradual
      increase in the risk of caesarean delivery and postpartum haemorrhage from age
      25, persisting after taking into account maternal BMI, hypertension and diabetes.
      The risk of low birthweight and preterm birth was elevated in women over 35.
      Further research is needed to understand the reasons behind the high prevalence
      of elective caesarean delivery in nulliparous older mothers.

PMID- 27716790
TI  - Cathepsin L Helps to Defend Mice from Infection with Influenza A.
AB  - Host-derived proteases can augment or help to clear infections. This dichotomy is
      exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus
      to invade cells, but is essential for survival in mice with mycoplasma pneumonia.
      The present study tested the hypothesis that CTSL protects mice from serious
      consequences of infection by the orthomyxovirus influenza A, which is thought to
      be activated by host-supplied proteases other than CTSL. Ctsl-/- mice infected
      with influenza A/Puerto Rico/8/34(H1N1) had larger lung viral loads and higher
      mortality than infected Ctsl+/+ mice. Lung inflammation in surviving infected
      mice peaked 14 days after initial infection, accompanied marked focal distal
      airway bronchiolization and epithelial metaplasia followed by desquamation and
      fibrotic interstitial remodeling, and persisted for at least 6 weeks. Most deaths
      occurred during the second week of infection in both groups of mice. In contrast
      to mycoplasma pneumonia, infiltrating cells were predominantly mononuclear rather
      than polymorphonuclear. The histopathology of lung inflammation and remodeling in
      survivors was similar in Ctsl-/- and Ctsl+/+ mice, although Ctsl+/+ mice cleared
      immunoreactive virus sooner. Furthermore, Ctsl-/- mice had profound deficits in
      CD4+ lymphocytes before and after infection and weaker production of pathogen
      specific IgG. Thus, CTSL appears to support innate as well as adaptive responses,
      which confer a survival advantage on mice infected with the orthomyxovirus
      influenza A.

PMID- 27716791
TI  - Molecular Mechanism of Silver Nanoparticles-Induced Human Osteoblast Cell Death:
      Protective Effect of Inducible Nitric Oxide Synthase Inhibitor.
AB  - BACKGROUND: Silver nanoparticles (AgNPs) show strong antibacterial properties,
      making them excellent candidates to be used in orthopaedic repair and
      regeneration. However, there are concerns regarding the cytotoxicity of AgNPs and
      molecular mechanisms underlying AgNPs-induced bone cells toxicity have not been
      elucidated. Therefore, the aim of our study was to explore mechanisms of AgNPs
      induced osteoblast cell death with particular emphasis on the role of nitric
      oxide (NO) generated by inducible nitric oxide synthase (iNOS). METHODS AND
      RESULT: Silver nanoparticles used in this study were 18.3+/-2.6 nm in size,
      uncoated, spherical, regular shape and their zeta potential was -29.1+/-2.4 mV as
      measured by transmission electron microscopy (TEM) and zetasizer. The release of
      silver (Ag) from AgNPs was measured in cell culture medium by atomic absorption
      spectroscopy (AAS). The exposure of human osteoblast cells (hFOB 1.19) to AgNPs
      at concentration of 30 or 60 MUg/mL for 24 or 48 hours, respectively resulted in
      cellular uptake of AgNPs and changes in cell ultrastructure. These changes were
      associated with apoptosis and necrosis as shown by flow cytometry and lactate
      dehydrogenase (LDH) assay as well as increased levels of pro-apoptotic Bax and
      decreased levels of anti-apoptotic Bcl-2 mRNA and protein. Importantly, we have
      found that AgNPs elevated the levels of nitric oxide (NO) with concomitant
      upregulation of inducible nitric oxide synthase (iNOS) mRNA and protein. A
      significant positive correlation was observed between the concentration of AgNPs
      and iNOS at protein and mRNA level (r = 0.837, r = 0.721, respectively; p<0.001).
      Finally, preincubation of osteoblast cells with N-iminoethyl-l-lysine (L-NIL), a
      selective iNOS inhibitor, as well as treating cells with iNOS small interfering
      RNAs (siRNA) significantly attenuated AgNPs-induced apoptosis and necrosis.
      Moreover, we have found that AgNPs-induced cells death is not related to Ag
      dissolution is cell culture medium. CONCLUSION: These results unambiguously
      demonstrate that increased expression of iNOS and generation of NO as well as NO
      derived reactive species is involved in AgNPs-induced osteoblast cell death. Our
      findings may help in development of new strategies to protect bone from AgNPs
      induced cytotoxicity and increase the safety of orthopaedic tissue repair.

PMID- 27716792
TI  - Lab-on-a-Chip-Based PCR-RFLP Assay for the Detection of Malayan Box Turtle (Cuora
      amboinensis) in the Food Chain and Traditional Chinese Medicines.
AB  - The Malayan box turtle (Cuora amboinensis) (MBT) is a vulnerable and protected
      turtle species, but it is a lucrative item in the illegal wildlife trade because
      of its great appeal as an exotic food item and in traditional medicine. Although
      several polymerase chain reaction (PCR) assays to identify MBT by various routes
      have been documented, their applicability for forensic authentication remains
      inconclusive due to the long length of the amplicon targets, which are easily
      broken down by natural decomposition, environmental stresses or physiochemical
      treatments during food processing. To address this research gap, we developed,
      for the first time, a species-specific PCR-restriction fragment length
      polymorphism (RFLP) assay with a very short target length (120 bp) to detect MBT
      in the food chain; this authentication ensured better security and reliability
      through molecular fingerprints. The PCR-amplified product was digested with Bfa1
      endonuclease, and distinctive restriction fingerprints (72, 43 and 5 bp) for MBT
      were found upon separation in a microfluidic chip-based automated electrophoresis
      system, which enhances the resolution of short oligos. The chances of any false
      negative identifications were eliminated through the use of a universal
      endogenous control for eukaryotes, and the limit of detection was 0.0001 ng DNA
      or 0.01% of the meat under admixed states. Finally, the optimized PCR-RFLP assay
      was validated for the screening of raw and processed commercial meatballs,
      burgers and frankfurters, which are very popular in most countries. The optimized
      PCR-RFLP assay was further used to screen MBT materials in 153 traditional
      Chinese medicines of 17 different brands and 62 of them were found MBT positive;
      wherein the ingredients were not declared in product labels. Overall, the novel
      assay demonstrated sufficient merit for use in any forensic and/or archaeological
      authentication of MBT, even under a state of decomposition.

PMID- 27716793
TI  - Outcomes Definitions and Statistical Tests in Oncology Studies: A Systematic
      Review of the Reporting Consistency.
AB  - BACKGROUND: Quality of reporting for Randomized Clinical Trials (RCTs) in
      oncology was analyzed in several systematic reviews, but, in this setting, there
      is paucity of data for the outcomes definitions and consistency of reporting for
      statistical tests in RCTs and Observational Studies (OBS). The objective of this
      review was to describe those two reporting aspects, for OBS and RCTs in oncology.
      METHODS: From a list of 19 medical journals, three were retained for analysis,
      after a random selection: British Medical Journal (BMJ), Annals of Oncology (AoO)
      and British Journal of Cancer (BJC). All original articles published between
      March 2009 and March 2014 were screened. Only studies whose main outcome was
      accompanied by a corresponding statistical test were included in the analysis.
      Studies based on censored data were excluded. Primary outcome was to assess
      quality of reporting for description of primary outcome measure in RCTs and of
      variables of interest in OBS. A logistic regression was performed to identify
      covariates of studies potentially associated with concordance of tests between
      Methods and Results parts. RESULTS: 826 studies were included in the review, and
      698 were OBS. Variables were described in Methods section for all OBS studies and
      primary endpoint was clearly detailed in Methods section for 109 RCTs (85.2%).
      295 OBS (42.2%) and 43 RCTs (33.6%) had perfect agreement for reported
      statistical test between Methods and Results parts. In multivariable analysis,
      variable "number of included patients in study" was associated with test
      consistency: aOR (adjusted Odds Ratio) for third group compared to first group
      was equal to: aOR Grp3 = 0.52 [0.31-0.89] (P value = 0.009). CONCLUSION:
      Variables in OBS and primary endpoint in RCTs are reported and described with a
      high frequency. However, statistical tests consistency between methods and
      Results sections of OBS is not always noted. Therefore, we encourage authors and
      peer reviewers to verify consistency of statistical tests in oncology studies.

PMID- 27716794
TI  - A Case-Crossover Study of Heat Exposure and Injury Risk in Outdoor Agricultural
      Workers.
AB  - BACKGROUND: Recent research suggests that heat exposure may increase the risk of
      traumatic injuries. Published heat-related epidemiological studies have relied
      upon exposure data from individual weather stations. OBJECTIVE: To evaluate the
      association between heat exposure and traumatic injuries in outdoor agricultural
      workers exposed to ambient heat and internal heat generated by physical activity
      using modeled ambient exposure data. METHODS: A case-crossover study using time
      stratified referent selection among 12,213 outdoor agricultural workers with new
      Washington State Fund workers' compensation traumatic injury claims between 2000
      and 2012 was conducted. Maximum daily Humidex exposures, derived from modeled
      meteorological data, were assigned to latitudes and longitudes of injury
      locations on injury and referent dates. Conditional logistic regression was used
      to estimate odds ratios of injury for a priori daily maximum Humidex categories.
      RESULTS: The mean of within-stratum (injury day and corresponding referent days)
      standard deviations of daily maximum Humidex was 4.8. The traumatic injury odds
      ratio was 1.14 (95% confidence interval 1.06, 1.22), 1.15 (95% confidence
      interval 1.06, 1.25), and 1.10 (95% confidence interval 1.01, 1.20) for daily
      maximum Humidex of 25-29, 30-33, and >=34, respectively, compared to < 25,
      adjusted for self-reported duration of employment. Stronger associations were
      observed during cherry harvest duties in the June and July time period, compared
      to all duties over the entire study period. CONCLUSIONS: Agricultural workers
      laboring in warm conditions are at risk for heat-related traumatic injuries.
      Combined heat-related illness and injury prevention efforts should be considered
      in high-risk populations exposed to warm ambient conditions in the setting of
      physical exertion.

PMID- 27716795
TI  - Effect of Glycosylation on an Immunodominant Region in the V1V2 Variable Domain
      of the HIV-1 Envelope gp120 Protein.
AB  - Heavy glycosylation of the envelope (Env) surface subunit, gp120, is a key
      adaptation of HIV-1; however, the precise effects of glycosylation on the
      folding, conformation and dynamics of this protein are poorly understood. Here we
      explore the patterns of HIV-1 Env gp120 glycosylation, and particularly the
      enrichment in glycosylation sites proximal to the disulfide linkages at the base
      of the surface-exposed variable domains. To dissect the influence of glycans on
      the conformation these regions, we focused on an antigenic peptide fragment from
      a disulfide bridge-bounded region spanning the V1 and V2 hyper-variable domains
      of HIV-1 gp120. We used replica exchange molecular dynamics (MD) simulations to
      investigate how glycosylation influences its conformation and stability.
      Simulations were performed with and without N-linked glycosylation at two sites
      that are highly conserved across HIV-1 isolates (N156 and N160); both are
      contacts for recognition by V1V2-targeted broadly neutralizing antibodies against
      HIV-1. Glycosylation stabilized the pre-existing conformations of this peptide
      construct, reduced its propensity to adopt other secondary structures, and
      provided resistance against thermal unfolding. Simulations performed in the
      context of the Env trimer also indicated that glycosylation reduces flexibility
      of the V1V2 region, and provided insight into glycan-glycan interactions in this
      region. These stabilizing effects were influenced by a combination of factors,
      including the presence of a disulfide bond between the Cysteines at 131 and 157,
      which increased the formation of beta-strands. Together, these results provide a
      mechanism for conservation of disulfide linkage proximal glycosylation adjacent
      to the variable domains of gp120 and begin to explain how this could be exploited
      to enhance the immunogenicity of those regions. These studies suggest that
      glycopeptide immunogens can be designed to stabilize the most relevant Env
      conformations to focus the immune response on key neutralizing epitopes.

PMID- 27716797
TI  - Risk of Recurrence in Laryngeal Cancer.
AB  - A cohort study was undertaken to analyze the risk of recurrence among 1616
      patients with primary squamous cell carcinoma of the larynx from 1983 to 2010 at
      a single, tertiary academic center in Oslo, Norway. The cohort was followed from
      the date of diagnosis to September 2011. Competing risk regression analysis
      assessed the association between various risk factors and the risk of recurrence,
      where death was considered a competing event. Recurrence was observed in 368
      patients (23%) during the study period. The majority (71%) of recurrences
      involved the location of the primary tumor. The overall risk of recurrence during
      the first three years after initiating treatment was 20.5%. Increased risk of
      recurrence was observed in patients with supraglottic cancer, younger patients,
      those with T2-T3 tumors and in patients treated in the earlier part of the study
      period. Significant factors for recurrence in glottic carcinomas were age,
      treatment in the earlier part of the study and T-status, whereas age was a
      significant factor in supraglottic cancer. N-status appeared less significant. In
      conclusion, follow-up of laryngeal squamous cell carcinoma should place
      particular emphasis on the site of the primary tumor, younger patients, cases of
      supraglottic cancer and T2-T4 primary tumors, especially during the first three
      years after treatment. More studies are needed to assess the impact of surgical
      versus non-surgical treatment, and eventually the significance of recurrence, for
      disease-specific and overall survival in cases of advanced laryngeal squamous
      cell carcinoma.

PMID- 27716796
TI  - Functional Trade-Offs in Promiscuous Enzymes Cannot Be Explained by Intrinsic
      Mutational Robustness of the Native Activity.
AB  - The extent to which an emerging new function trades off with the original
      function is a key characteristic of the dynamics of enzyme evolution. Various
      cases of laboratory evolution have unveiled a characteristic trend; a large
      increase in a new, promiscuous activity is often accompanied by only a mild
      reduction of the native, original activity. A model that associates weak trade
      offs with "evolvability" was put forward, which proposed that enzymes possess
      mutational robustness in the native activity and plasticity in promiscuous
      activities. This would enable the acquisition of a new function without
      compromising the original one, reducing the benefit of early gene duplication and
      therefore the selection pressure thereon. Yet, to date, no experimental study has
      examined this hypothesis directly. Here, we investigate the causes of weak trade
      offs by systematically characterizing adaptive mutations that occurred in two
      cases of evolutionary transitions in enzyme function: (1) from phosphotriesterase
      to arylesterase, and (2) from atrazine chlorohydrolase to melamine deaminase.
      Mutational analyses in various genetic backgrounds revealed that, in contrast to
      the prevailing model, the native activity is less robust to mutations than the
      promiscuous activity. For example, in phosphotriesterase, the deleterious effect
      of individual mutations on the native phosphotriesterase activity is much larger
      than their positive effect on the promiscuous arylesterase activity. Our
      observations suggest a revision of the established model: weak trade-offs are not
      caused by an intrinsic robustness of the native activity and plasticity of the
      promiscuous activity. We propose that upon strong adaptive pressure for the new
      activity without selection against the original one, selected mutations will lead
      to the largest possible increases in the new function, but whether and to what
      extent they decrease the old function is irrelevant, creating a bias towards
      initially weak trade-offs and the emergence of generalist enzymes.

PMID- 27716798
TI  - MicroNeurotrophins Improve Survival in Motor Neuron-Astrocyte Co-Cultures but Do
      Not Improve Disease Phenotypes in a Mutant SOD1 Mouse Model of Amyotrophic
      Lateral Sclerosis.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease caused by loss
      of motor neurons. ALS patients experience rapid deterioration in muscle function
      with an average lifespan of 3-5 years after diagnosis. Currently, the most
      effective therapeutic only extends lifespan by a few months, thus highlighting
      the need for new and improved therapies. Neurotrophic factors (NTFs) are
      important for neuronal development, maintenance, and survival. NTF treatment has
      previously shown efficacy in pre-clinical ALS models. However, clinical trials
      using NTFs produced no major improvements in ALS patients, due in part to the
      limited blood brain barrier (BBB) penetration. In this study we assessed the
      potential neuroprotective effects of a novel class of compounds known as
      MicroNeurotrophins (MNTs). MNTs are derivatives of Dehydroepiandrosterone (DHEA),
      an endogenous neurosteroid that can cross the BBB and bind to tyrosine kinase
      receptors mimicking the pro-survival effects of NTFs. Here we sought to determine
      whether MNTs were neuroprotective in two different models of ALS. Our results
      demonstrate that BNN27 (10 MUM) attenuated loss of motor neurons co-cultured with
      astrocytes derived from human ALS patients with SOD1 mutations via the reduction
      of oxidative stress. Additionally, in the G93A SOD1 mouse, BNN27 (10 mg/kg)
      treatment attenuated motor behavioral impairment in the paw grip endurance and
      rotarod tasks at postnatal day 95 in female but not male mice. In contrast, BNN27
      (10 mg/kg and 50 mg/kg) treatment did not alter any other behavioral outcome or
      neuropathological marker in male or female mice. Lastly, BNN27 was not detected
      in post-mortem brain or spinal cord tissue of treated mice due to the rapid
      metabolism of BNN27 by mouse hepatocytes relative to human hepatocytes. Together,
      these findings demonstrate that BNN27 treatment failed to yield significant
      neuroprotective effects in the G93A SOD1 model likely due to its rapid rate of
      metabolism in mice.

PMID- 27716800
TI  - Re-Evaluation of Phylogenetic Relationships among Species of the Mangrove Genus
      Avicennia from Indo-West Pacific Based on Multilocus Analyses.
AB  - Avicennia L. (Avicenniaceae), one of the most diverse mangrove genera, is
      distributed widely in tropical and subtropical intertidal zones worldwide. Five
      species of Avicennia in the Indo-West Pacific region have been previously
      described. However, their phylogenetic relationships were determined based on
      morphological and allozyme data. To enhance our understanding of evolutionary
      patterns in the clade, we carried out a molecular phylogenetic study using wide
      sampling and multiple loci. Our results support two monophyletic clades across
      all species worldwide in Avicennia: an Atlantic-East Pacific (AEP) lineage and an
      Indo-West Pacific (IWP) lineage. This split is in line with biogeographic
      distribution of the clade. Focusing on the IWP branch, we reconstructed a
      detailed phylogenetic tree based on sequences from 25 nuclear genes. The results
      identified three distinct subclades, (1) A. rumphiana and A. alba, (2) A.
      officinalis and A. integra, and (3) the A. marina complex, with high bootstrap
      support. The results strongly corresponded to two morphological traits in floral
      structure: stigma position in relation to the anthers and style length. Using
      Bayesian dating methods we estimated diversification of the IWP lineage was dated
      to late Miocene (c. 6.0 million years ago) and may have been driven largely by
      the fluctuating sea levels since that time.

PMID- 27716799
TI  - Rapid and Objective Assessment of Neural Function in Autism Spectrum Disorder
      Using Transient Visual Evoked Potentials.
AB  - OBJECTIVE: There is a critical need to identify biomarkers and objective outcome
      measures that can be used to understand underlying neural mechanisms in autism
      spectrum disorder (ASD). Visual evoked potentials (VEPs) offer a noninvasive
      technique to evaluate the functional integrity of neural mechanisms, specifically
      visual pathways, while probing for disease pathophysiology. METHODS: Transient
      VEPs (tVEPs) were obtained from 96 unmedicated children, including 37 children
      with ASD, 36 typically developing (TD) children, and 23 unaffected siblings
      (SIBS). A conventional contrast-reversing checkerboard condition was compared to
      a novel short-duration condition, which was developed to enable objective data
      collection from severely affected populations who are often excluded from
      electroencephalographic (EEG) studies. RESULTS: Children with ASD showed
      significantly smaller amplitudes compared to TD children at two of the earliest
      critical VEP components, P60-N75 and N75-P100. SIBS showed intermediate responses
      relative to ASD and TD groups. There were no group differences in response
      latency. Frequency band analyses indicated significantly weaker responses for the
      ASD group in bands encompassing gamma-wave activity. Ninety-two percent of
      children with ASD were able to complete the short-duration condition compared to
      68% for the standard condition. CONCLUSIONS: The current study establishes the
      utility of a short-duration tVEP test for use in children at varying levels of
      functioning and describes neural abnormalities in children with idiopathic ASD.
      Implications for excitatory/inhibitory balance as well as the potential
      application of VEP for use in clinical trials are discussed.

PMID- 27716801
TI  - Sympathy Crying: Insights from Infrared Thermal Imaging on a Female Sample.
AB  - Sympathy crying is an odd and complex mixture of physiological and emotional
      phenomena. Standard psychophysiological theories of emotion cannot attribute
      crying to a single subdivision of the autonomic nervous system (ANS) and
      disagreement exists regarding the emotional origin of sympathy crying. The
      current experiment examines sympathy crying using functional thermal infrared
      imaging (FTII), a novel contactless measure of ANS activity. To induce crying
      female participants were given the choice to decide which film they wanted to cry
      to. Compared to baseline, temperature started increasing on the forehead, the
      peri-orbital region, the cheeks and the chin before crying and reached even
      higher temperatures during crying. The maxillary area showed the opposite pattern
      and a gradual temperature decrease was observed compared to baseline as a result
      of emotional sweating. The results suggest that tears of sympathy are part of a
      complex autonomic interaction between the sympathetic and the parasympathetic
      nervous systems, with the latter preceding the former. The emotional origin of
      the phenomenon seems to derive from subjective internal factors that relate to
      one's personal experiences and attributes with tears arising in the form of
      catharses or as part of shared sadness.

PMID- 27716803
TI  - Major Shift of Toxigenic V. cholerae O1 from Ogawa to Inaba Serotype Isolated
      from Clinical and Environmental Samples in Haiti.
AB  - In October of 2010, an outbreak of cholera was confirmed in Haiti for the first
      time in more than a century. A single clone of toxigenic Vibrio cholerae O1
      biotype El Tor serotype Ogawa strain was implicated as the cause. Five years
      after the onset of cholera, in October, 2015, we have discovered a major switch
      (ranging from 7 to 100%) from Ogawa serotype to Inaba serotype. Furthermore,
      using wbeT gene sequencing and comparative sequence analysis, we now demonstrate
      that, among 2013 and 2015 Inaba isolates, the wbeT gene, responsible for
      switching Ogawa to Inaba serotype, sustained a unique nucleotide mutation not
      found in isolates obtained from Haiti in 2012. Moreover, we show that,
      environmental Inaba isolates collected in 2015 have the identical mutations found
      in the 2015 clinical isolates. Our data indicate that toxigenic V. cholerae O1
      serotype Ogawa can rapidly change its serotype to Inaba, and has the potential to
      cause disease in individuals who have acquired immunity against Ogawa serotype.
      Our findings highlight the importance of monitoring of toxigenic V. cholerae O1
      and cholera in countries with established endemic disease.

PMID- 27716802
TI  - Transcriptome Analysis of Gene Expression during Chinese Water Chestnut Storage
      Organ Formation.
AB  - The product organ (storage organ; corm) of the Chinese water chestnut has become
      a very popular food in Asian countries because of its unique nutritional value.
      Corm formation is a complex biological process, and extensive whole genome
      analysis of transcripts during corm development has not been carried out. In this
      study, four corm libraries at different developmental stages were constructed,
      and gene expression was identified using a high-throughput tag sequencing
      technique. Approximately 4.9 million tags were sequenced, and 4,371,386,
      4,372,602, 4,782,494, and 5,276,540 clean tags, including 119,676, 110,701,
      100,089, and 101,239 distinct tags, respectively, were obtained after removal of
      low-quality tags from each library. More than 39% of the distinct tags were
      unambiguous and could be mapped to reference genes, while 40% were unambiguous
      tag-mapped genes. After mapping their functions in existing databases, a total of
      11,592, 10,949, 10,585, and 7,111 genes were annotated from the B1, B2, B3, and
      B4 libraries, respectively. Analysis of the differentially expressed genes (DEGs)
      in B1/B2, B2/B3, and B3/B4 libraries showed that most of the DEGs at the B1/B2
      stages were involved in carbohydrate and hormone metabolism, while the majority
      of DEGs were involved in energy metabolism and carbohydrate metabolism at the
      B2/B3 and B3/B4 stages. All of the upregulated transcription factors and 9
      important genes related to product organ formation in the above four stages were
      also identified. The expression changes of nine of the identified DEGs were
      validated using a quantitative PCR approach. This study provides a comprehensive
      understanding of gene expression during corm formation in the Chinese water
      chestnut.

PMID- 27716805
TI  - How Metabolic Diseases Impact the Use of Antimicrobials: A Formal Demonstration
      in the Field of Veterinary Medicine.
AB  - Decreasing the use of antimicrobials has become a primary objective for both
      human and veterinary medicine in many countries. Medical prevention and good
      nutrition are seen as key parameters for reducing antimicrobial use. However,
      little consideration has been given to how metabolic diseases may influence the
      use of antimicrobials in humans and animals through limiting the prevalence and
      severity of infectious diseases. To quantify this relationship using the example
      of a common metabolic disease in dairy cows (subclinical ketosis, SCK), we
      constructed a stochastic model reporting the total quantity of curative
      antimicrobials for a given population with the prevalence of cows at risk for
      SCK. We considered the prevalence of SCK, the relative risk of the disease in
      cases of SCK compared to no SCK and the use of antimicrobials to treat SCK
      induced infectious diseases. Reducing the percentage of cows at risk for SCK from
      80% to 10% was associated with an average decrease in the use of antimicrobials
      of 11% (prevalence of SCK from 34% to 17%, respectively) or 25% (prevalence of
      SCK from 68% to 22%, respectively), depending on the relative risk to contract
      SCK if risk was present. For a large percentage of the cows at risk for SCK,
      using a preventive bolus of monensin reduced the use of curative antimicrobials
      to the same level that was observed when the percentage of cows at risk for SCK
      was low. The present work suggests similar approaches for obesity and diabetes.

PMID- 27716804
TI  - The Sero-epidemiology of Coxiella burnetii in Humans and Cattle, Western Kenya:
      Evidence from a Cross-Sectional Study.
AB  - Evidence suggests that the intracellular bacterial pathogen Coxiella burnetii
      (which causes Q fever) is widespread, with a near global distribution. While
      there has been increasing attention to Q fever epidemiology in high-income
      settings, a recent systematic review highlighted significant gaps in our
      understanding of the prevalence, spatial distribution and risk factors for Q
      fever infection across Africa. This research aimed to provide a One Health
      assessment of Q fever epidemiology in parts of Western and Nyanza Provinces,
      Western Kenya, in cattle and humans. A cross-sectional survey was conducted:
      serum samples from 2049 humans and 955 cattle in 416 homesteads were analysed for
      C. burnetii antibodies. Questionnaires covering demographic, socio-economic and
      husbandry information were also administered. These data were linked to
      environmental datasets based on geographical locations (e.g., land cover).
      Correlation and spatial-cross correlation analyses were applied to assess the
      potential link between cattle and human seroprevalence. Multilevel regression
      analysis was used to assess the relationships between a range of socio-economic,
      demographic and environmental factors and sero-positivity in both humans and
      animals. The overall sero-prevalence of C. burnetii was 2.5% in humans and 10.5%
      in cattle, but we found no evidence of correlation between cattle and human
      seroprevalence either within households, or when incorporating spatial proximity
      to other households in the survey. Multilevel modelling indicated the importance
      of several factors for exposure to the organism. Cattle obtained from market (as
      opposed to those bred in their homestead) and those residing in areas with lower
      precipitation levels had the highest sero-prevalence. For humans, the youngest
      age group had the highest odds of seropositivity, variations were observed
      between ethnic groups, and frequent livestock contact (specifically grazing and
      dealing with abortion material) was also a risk factor. These results illustrate
      endemicity of C. burnetii in western Kenya, although prevalence is relatively
      low. The analysis indicates that while environmental factors may play a role in
      cattle exposure patterns, human exposure patterns are likely to be driven more
      strongly by livestock contacts. The implication of livestock markets in cattle
      exposure risks suggests these may be a suitable target for interventions.

PMID- 27716806
TI  - Evidence of In Vivo Absorption of Lactate and Modulation of Short Chain Fatty
      Acid Absorption from the Reticulorumen of Non-Lactating Cattle Fed High
      Concentrate Diets.
AB  - Short-chain fatty acids (SCFAs) and lactate are endproducts of rumen fermentation
      and important energy sources for the host ruminant. Because their rapid
      accumulation results in ruminal acidosis, enhancement of the absorption of SCFA
      and lactate across reticuloruminal wall is instrumental in increasing energy
      supply and preventing ruminal acidosis in cattle. This study investigated whether
      the reticuloruminal absorption of SCFAs and lactate was altered by different
      strategies of high concentrate feeding. Eight rumen-cannulated, non-lactating
      Holstein cows were fed a forage-only diet (baseline) and then gradually adapted
      over 6 d to a 60% concentrate level. Thereafter, this concentrate-rich diet was
      fed for 4 wk either continuously (Con; n = 8) or interruptedly (Int; n = 8).
      Absorption of SCFAs and lactate was determined in vivo from the experimental
      buffer introduced into the washed reticulorumen. The buffer contained acetate,
      propionate, butyrate and lactate at a concentration of 60, 30, 10 and 5 mmol/L,
      respectively and Cr-EDTA as a marker for correcting ruminal water fluxes. The
      reticuloruminal absorption after 35 and 65 min of buffer incubation was measured
      at the baseline, after 1 wk of 60% concentrate feeding in the interrupted model
      (Int-1) and after 4 wk of concentrate feeding in both feeding models (Int-4 and
      Con-4). Data showed that the absorption rates of individual and total SCFAs
      during the first 35 min of incubation of Con-4 were highest (~1.7 times compared
      to baseline), while Int-1 and Int-4 were similar to respective baseline. Lactate
      was not absorbed during forage-only baseline and 1-wk concentrate feeding, but
      after 4-wk feeding of concentrates in both models. In conclusion, SCFAs
      absorption across the reticulorumen of non-lactating cattle was enhanced by the 4
      wk continuous concentrate feeding, which seems to be more advantageous in terms
      of rumen acidosis prevention compared to the interrupted feeding model. The study
      provides evidence of lactate absorption across the reticulorumen of non-lactating
      cattle after both continuous and interrupted 4-wk concentrate feeding.

PMID- 27716807
TI  - Local Transcriptional Control of YUCCA Regulates Auxin Promoted Root-Growth
      Inhibition in Response to Aluminium Stress in Arabidopsis.
AB  - Auxin is necessary for the inhibition of root growth induced by aluminium (Al)
      stress, however the molecular mechanism controlling this is largely unknown.
      Here, we report that YUCCA (YUC), which encodes flavin monooxygenase-like
      proteins, regulates local auxin biosynthesis in the root apex transition zone
      (TZ) in response to Al stress. Al stress up-regulates YUC3/5/7/8/9 in the root
      apex TZ, which we show results in the accumulation of auxin in the root-apex TZ
      and root-growth inhibition during the Al stress response. These Al-dependent
      changes in the regulation of YUCs in the root-apex TZ and YUC-regulated root
      growth inhibition are dependent on ethylene signalling. Increasing or disruption
      of ethylene signalling caused either enhanced or reduced up-regulation,
      respectively, of YUCs in root-apex TZ in response to Al stress. In addition,
      ethylene enhanced root growth inhibition under Al stress was strongly alleviated
      in yuc mutants or by co-treatment with yucasin, an inhibitor of YUC activity,
      suggesting a downstream role of YUCs in this process. Moreover, ethylene
      insensitive 3 (EIN3) is involved into the direct regulation of YUC9 transcription
      in this process. Furthermore, we demonstrated that PHYTOCHROME INTERACTING
      FACTOR4 (PIF4) functions as a transcriptional activator for YUC5/8/9. PIF4
      promotes Al-inhibited primary root growth by regulating the local expression of
      YUCs and auxin signal in the root-apex TZ. The Al-induced expression of PIF4 in
      root TZ acts downstream of ethylene signalling. Taken together, our results
      highlight a regulatory cascade for YUCs-regulated local auxin biosynthesis in the
      root-apex TZ mediating root growth inhibition in response to Al stress.

PMID- 27716808
TI  - Bovine Lhx8, a Germ Cell-Specific Nuclear Factor, Interacts with Figla.
AB  - LIM homeobox 8 (Lhx8) is a germ cell-specific transcription factor essential for
      the development of oocytes during early oogenesis. In mice, Lhx8 deficiency
      causes postnatal oocyte loss and affects the expression of many oocyte-specific
      genes. The aims of this study were to characterize the bovine Lhx8 gene,
      determine its mRNA expression during oocyte development and early embryogenesis,
      and evaluate its interactions with other oocyte-specific transcription factors.
      The bovine Lhx8 gene encodes a protein of 377 amino acids. A splice variant of
      Lhx8 (Lhx8_v1) was also identified. The predicted bovine Lhx8 protein contains
      two LIM domains and one homeobox domain. However, one of the LIM domains in
      Lhx8_v1 is incomplete due to deletion of 83 amino acids near the N terminus. Both
      Lhx8 and Lhx8_v1 transcripts were only detected in the gonads but none of the
      somatic tissues examined. The expression of Lhx8 and Lhx8_v1 appears to be
      restricted to oocytes as none of the transcripts was detectable in granulosa or
      theca cells. The maternal Lhx8 transcript is abundant in GV and MII stage oocytes
      as well as in early embryos but disappear by morula stage. A nuclear localization
      signal that is required for the import of Lhx8 into nucleus was identified, and
      Lhx8 is predominantly localized in the nucleus when ectopically expressed in
      mammalian cells. Finally, a novel interaction between Lhx8 and Figla, another
      transcription factor essential for oogenesis, was detected. The results provide
      new information for studying the mechanisms of action for Lhx8 in oocyte
      development and early embryogenesis.

PMID- 27716809
TI  - A High-Throughput Small Molecule Screen for C. elegans Linker Cell Death
      Inhibitors.
AB  - Programmed cell death is a ubiquitous process in metazoan development. Apoptosis,
      one cell death form, has been studied extensively. However, mutations
      inactivating key mammalian apoptosis regulators do not block most developmental
      cell culling, suggesting that other cell death pathways are likely important.
      Recent work in the nematode Caenorhabditis elegans identified a non-apoptotic
      cell death form mediating the demise of the male-specific linker cell. This cell
      death process (LCD, linker cell-type death) is morphologically conserved, and its
      molecular effectors also mediate axon degeneration in mammals and Drosophila. To
      develop reagents to manipulate LCD, we established a simple high-throughput
      screening protocol for interrogating the effects of small molecules on C. elegans
      linker cell death in vivo. From 23,797 compounds assayed, 11 reproducibly block
      linker cell death onset. Of these, five induce animal lethality, and six promote
      a reversible developmental delay. These results provide proof-of principle
      validation of our screening protocol, demonstrate that developmental progression
      is required for linker cell death, and suggest that larger scale screens may
      identify LCD-specific small-molecule regulators that target the LCD execution
      machinery.

PMID- 27716810
TI  - Associations of Serum Levels of Sex Hormones in Follicular and Luteal Phases of
      the Menstrual Cycle with Breast Tissue Characteristics in Young Women.
AB  - BACKGROUND: In previous work in young women aged 15-30 years we measured breast
      water and fat using MR and obtained blood for hormone assays on the same day in
      the follicular phase of the menstrual cycle. Only serum growth hormone levels and
      sex hormone binding globulin (SHBG) were significantly associated with percent
      breast water after adjustment for covariates. The sex hormones estradiol,
      progesterone and testosterone were not associated with percent water in the
      breast in the follicular phase of the menstrual cycle. In the present study we
      have examined the association of percent breast water with serum levels of sex
      hormones in both follicular and luteal phase of the menstrual cycle. METHODS: In
      315 healthy white Caucasian young women aged 15-30 with regular menstrual cycles
      who had not used oral contraceptives or other hormones in the previous 6 months,
      we used MR to determine percent breast water, and obtained blood samples for
      hormone assays within 10 days of the onset of the most recent menstrual cycle
      (follicular phase) of the cycle on the same day as the MR scan, and a second
      blood sample on days 19-24 of the cycle. Serum progesterone levels of > = 5
      mmol/L in days 19-24 were used to define the 225 subjects with ovulatory
      menstrual cycles, whose data are the subject of the analyses shown here. RESULTS:
      SHBG was positively associated with percent water in both follicular and luteal
      phases of the menstrual cycle. Total and free estradiol and total and free
      testosterone were not associated with percent water in the follicular phase, but
      in young women with ovulatory cycles, were all negatively associated with percent
      water in the luteal phase. CONCLUSIONS: Our results from young women aged 15-30
      years add to the evidence that the extent of fibroglandular tissue in the breast
      that is reflected in both mammographic density and breast water is associated
      positively with higher serum levels of SHBG, but not with higher levels of sex
      hormones.

PMID- 27716811
TI  - Risk Factors and Clinical Outcomes in Preterm Infants with Pulmonary
      Hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a significant cause of morbidity in
      preterm infants, but no screening guidelines exist. We sought to identify risk
      factors and clinical outcomes associated with PH in preterm infants to develop a
      PH risk score. METHODS: Retrospective analysis of two separate populations of
      preterm infants (NICU cohort n = 230; Clinic registry n = 580). RESULTS: 8.3% of
      the NICU cohort had PH after 4 weeks of age, while 14.8% of the clinic registry
      had PH after 2 months of age. Lower birth weights and longer initial
      hospitalizations were associated with PH in both populations (p<0.001 for all
      tests). Using adjusted logistic regression, patent ductus arteriosus (PDA)
      requiring ligation was associated with PH in both the NICU cohort (OR: 3.19; p =
      0.024) and the clinic registry (OR: 2.67; p<0.001). Risk factors (birth weight
      <=780 grams, home supplemental oxygen use, and PDA ligation) identified in the
      clinic registry (training dataset) were validated in the NICU cohort with 0-1
      factors present were associated with <=1.5% probability of having PH, any 2
      factors with a 25% probability, and all 3 factors with a 40% probability.
      CONCLUSIONS: Lower birth weight, PDA ligation, and respiratory support were
      associated with PH in both populations. A PH risk score based on clinical
      indicators from the training dataset predicted PH in the validation set. This
      risk score could help focus resources to preterm infants at higher risk for PH.
      Further work is needed to determine whether earlier or more aggressive management
      of ductal lesions could alter PH outcomes.

PMID- 27716812
TI  - Use of Warning Signs for Dengue by Pediatric Health Care Staff in Brazil.
AB  - OBJECTIVE: The aim of this study was to describe the use of dengue warning signs
      by pediatric healthcare staff in the Brazilian public health care system.
      METHODS: Cross-sectional study (2012) with physicians, nurses, and nurse
      technicians assisting children in five health care facilities. Participants
      reported the use and importance of dengue warning signs in pediatrics clinical
      practice through a structured questionnaire. Differences in the use of signs (chi
      square test) and in the ranking assigned to each of them (Kruskal-Wallis) were
      assessed according to health care occupation and level of care (p<0.05). RESULTS:
      The final sample comprised 474 participants (97%), mean age of 37 years (standard
      deviation = 10.3), mainly females (83.8%), physicians (40.1%) and from tertiary
      care (75.1%). The majority (91%) reported using warning signs for dengue in
      pediatrics clinical practice. The most widely used and highly valued signs were
      major hemorrhages (gastrointestinal, urinary), abdominal pain, and increase in
      hematocrit concurrent or not with rapid decrease in platelet count. Persistent
      vomiting as well as other signs of plasma leakage such as respiratory distress
      and lethargy/restlessness were not identified as having the same degree of
      importance, especially by nurse technicians and in primary or secondary care.
      DISCUSSION: Although most health care staff reported using dengue warning signs,
      it would be useful to extend the training for identifying easily recognizable
      signs of plasma leakage that occur regardless of bleeding.

PMID- 27716813
TI  - Human Resources for Treating HIV/AIDS: Are the Preventive Effects of
      Antiretroviral Treatment a Game Changer?
AB  - Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental
      barrier to reaching universal antiretroviral treatment (ART) coverage in
      developing countries. Previous studies suggest that recruiting HRHA to attain
      universal ART coverage poses an insurmountable challenge as ART significantly
      increases survival among HIV-infected individuals. While new evidence about ART's
      prevention benefits suggests fewer infections may mitigate the challenge, new
      policies such as treatment-as-prevention (TasP) will exacerbate it. We develop a
      mathematical model to analytically study the net effects of these countervailing
      factors. Using South Africa as a case study, we find that contrary to previous
      results, universal ART coverage is achievable even with current HRHA numbers.
      However, larger health gains are possible through a surge-capacity policy that
      aggressively recruits HRHA to reach universal ART coverage quickly. Without such
      a policy, TasP roll-out can increase health losses by crowding out sicker
      patients from treatment, unless a surge capacity exclusively for TasP is also
      created.

PMID- 27716815
TI  - Bounded Confidence under Preferential Flip: A Coupled Dynamics of Structural
      Balance and Opinions.
AB  - In this work we study the coupled dynamics of social balance and opinion
      formation. We propose a model where agents form opinions under bounded
      confidence, but only considering the opinions of their friends. The signs of
      social ties -friendships and enmities- evolve seeking for social balance, taking
      into account how similar agents' opinions are. We consider both the case where
      opinions have one and two dimensions. We find that our dynamics produces the
      segregation of agents into two cliques, with the opinions of agents in one clique
      differing from those in the other. Depending on the level of bounded confidence,
      the dynamics can produce either consensus of opinions within each clique or the
      coexistence of several opinion clusters in a clique. For the uni-dimensional
      case, the opinions in one clique are all below the opinions in the other clique,
      hence defining a "left clique" and a "right clique". In the two-dimensional case,
      our numerical results suggest that the two cliques are separated by a hyperplane
      in the opinion space. We also show that the phenomenon of unidimensional opinions
      identified by DeMarzo, Vayanos and Zwiebel (Q J Econ 2003) extends partially to
      our dynamics. Finally, in the context of politics, we comment about the possible
      relation of our results to the fragmentation of an ideology and the emergence of
      new political parties.

PMID- 27716816
TI  - Monetary Expansion and the Banking Lending Channel.
AB  - This paper examines the bank lending channel, which considers how monetary
      authority actions affect the variation of loans. We focus on the BRICS (Brazil,
      Russia, India, China and South Africa) totalizing 1254 banks from five countries
      in the period 2000-2012 (totalizing 13 years). The empirical results show that
      the effect of money supply growth on the growth of loans is non-linear and
      inverted U-shaped. In this context, our results show empirical evidence
      expansionary monetary policies do not increase the propensity of economic agents
      to systematically take greater risks on the market. After a certain level of
      money stock, increases in the money supply do not lead to increased negotiated
      credit.

PMID- 27716814
TI  - Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced
      Neuropathy.
AB  - INTRODUCTION: Sensory peripheral neuropathy caused by paclitaxel is a common and
      dose limiting toxicity, for which there are currently no validated predictive
      biomarkers. We investigated the relationship between the Charcot-Marie-Tooth
      protein NDRG1 and paclitaxel-induced neuropathy. METHODS/MATERIALS: Archived
      mammary tissue specimen blocks of breast cancer patients who received weekly
      paclitaxel in a single centre were retrieved and NDRG1 immunohistochemistry was
      performed on normal nerve tissue found within the sample. The mean nerve NDRG1
      score was defined by an algorithm based on intensity of staining and percentage
      of stained nerve bundles. NDRG1 scores were correlated with paclitaxel induced
      neuropathy. RESULTS: 111 patients were studied. 17 of 111 (15%) developed severe
      paclitaxel-induced neuropathy. The mean nerve NDRG1 expression score was 5.4 in
      patients with severe neuropathy versus 7.7 in those without severe neuropathy (p
      = 0.0019). A Receiver operating characteristic (ROC) curve analysis of the mean
      nerve NDRG1 score revealed an area under the curve of 0.74 (p = 0.0013) for the
      identification of severe neuropathy, with a score of 7 being most discriminative.
      13/54 (24%) subjects with an NDRG1 score < = 7 developed severe neuropathy,
      compared to only 4/57 (7%) in those with a score >7 (p = 0.017). CONCLUSION: Low
      NDRG1 expression in nerve tissue present within samples of surgical resection may
      identify subjects at risk for severe paclitaxel-induced neuropathy. Since nerve
      biopsies are not routinely feasible for patients undergoing chemotherapy for
      early breast cancer, this promising biomarker strategy is compatible with current
      clinical workflow.

PMID- 27716817
TI  - Context-Dependent Egr1 Expression in the Avian Hippocampus.
AB  - In mammals, episodic memory and spatial cognition involve context-specific
      recruitment of unique ensembles in the hippocampal formation (HF). Despite their
      capacity for sophisticated spatial (e.g., for migration) and episodic-like (e.g.,
      for food-caching) memory, the mechanisms underlying contextual representation in
      birds is not well understood. Here we demonstrate environment-specific Egr1
      expression as male brown-headed cowbirds (Molothrus ater) navigate environments
      for food reward, showing that the avian HF, like its mammalian counterpart,
      recruits distinct neuronal ensembles to represent different contexts.

PMID- 27716818
TI  - Impact of Age and Sex on CD4+ Cell Count Trajectories following Treatment
      Initiation: An Analysis of the Tanzanian HIV Treatment Database.
AB  - OBJECTIVE: New guidelines recommend that all HIV-infected individuals initiate
      antiretroviral treatment (ART) immediately following diagnosis. This study
      describes how immune reconstitution varies by gender and age to help identify
      poorly reconstituting subgroups and inform targeted testing initiatives. DESIGN:
      Longitudinal data from the outpatient monitoring system of the National AIDS
      Control Program in Tanzania. METHODS: An asymptotic nonlinear mixed effects model
      was fit to post-treatment CD4+ cell count trajectories, allowing for fixed
      effects of age and sex, and an age by sex interaction. RESULTS: Across 220,544
      clinic visits from 32,069 HIV-infected patients, age- and sex-specific average
      CD4+ cell count at ART initiation ranged from 83-136 cells/mm3, long term
      asymptotic CD4+ cell count ranged from 301-389 cells/mm3, and time to half of
      maximal CD4+ reconstitution ranged from 3.57-5.68 months. CD4+ cell count at ART
      initiation and asymptotic CD4+ cell count were 1.28 (95% CI: 1.18-1.40) and 1.25
      (95% CI: 1.20-1.31) times higher, respectively, for females compared to males in
      the youngest age group (19-29 years). Older patients started treatment at higher
      CD4+ counts but experienced slower CD4+ recovery than younger adults. Treatment
      initiation at greater CD4+ cell counts was correlated with greater asymptotic
      CD4+ cell counts within all sex and age groups. CONCLUSION: Older adults should
      initiate care early in disease progression because total immune reconstitution
      potential and rate of reconstitution appears to decrease with age. Targeted HIV
      testing and care linkage remains crucial for patient populations who tend to
      initiate treatment at lower CD4+ cell counts, including males and younger adults.

PMID- 27716821
TI  - Correction: DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring
      Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1005788.].

PMID- 27716819
TI  - A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib
      Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid
      Leukemia.
AB  - : Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR
      1/-2/-3 and PDGFR-alpha/-beta, exerts growth inhibitory and pro-apoptotic effects
      in myeloid leukemic cells, especially when used in combination with cytarabine.
      This phase I study evaluated nintedanib in combination with low-dose cytarabine
      (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid
      leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib
      (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg
      subcutaneous injection twice daily for 10 days) were administered in 28-day
      cycles. Dose-limiting toxicity (DLT) was defined as non-hematological severe
      adverse reaction CTC grade >= 4 with possible or definite relationship to
      nintedanib. Between April 2012 and October 2013, 13 patients (median age 73
      [range: 62-86] years) were enrolled. One patient did not receive study medication
      and was replaced. Nine (69%) patients had relapsed or refractory disease and 6
      (46%) patients had unfavorable cytogenetics. The most frequently reported
      treatment-related adverse events (AE) were gastrointestinal events. Twelve SAEs
      irrespective of relatedness were reported. Two SUSARs were observed, one fatal
      hypercalcemia and one fatal gastrointestinal infection. Two patients (17%) with
      relapsed AML achieved a complete remission (one CR, one CRi) and bone marrow
      blast reductions without fulfilling PR criteria were observed in 3 patients
      (25%). One-year overall survival was 33%. Nintedanib combined with LDAC shows an
      adequate safety profile and survival data are promising in a difficult-to-treat
      patient population. Continuation of this trial with a phase II recommended dose
      of 2 x 200 mg nintedanib in a randomized, placebo-controlled phase II study is
      planned. The trial is registered to EudraCT as 2011-001086-41. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01488344.

PMID- 27716820
TI  - Gdown1 Associates Efficiently with RNA Polymerase II after Promoter Clearance and
      Displaces TFIIF during Transcript Elongation.
AB  - Pausing during the earliest stage of transcript elongation by RNA polymerase II
      (Pol II) is a nearly universal control point in metazoan gene expression. The
      substoichiometric Pol II subunit Gdown1 facilitates promoter proximal pausing in
      vitro in extract-based transcription reactions, out-competes the
      initiation/elongation factor TFIIF for binding to free Pol II and co-localizes
      with paused Pol II in vivo. However, we have shown that Gdown1 cannot
      functionally associate with the Pol II preinitiation complex (PIC), which
      contains TFIIF. In the present study, we determined at what point after
      initiation Gdown1 can associate with Pol II and how rapidly this competition with
      TFIIF occurs. We show that, as with the PIC, Gdown1 cannot functionally load into
      open complexes or complexes engaged in abortive synthesis of very short RNAs.
      Gdown1 can load into early elongation complexes (EECs) with 5-9 nt RNAs, but
      efficient association with EECs does not take place until the point at which the
      upstream segment of the long initial transcription bubble reanneals. Tests of
      EECs assembled on a series of promoter variants confirm that this bubble collapse
      transition, and not transcript length, modulates Gdown1 functional affinity.
      Gdown1 displaces TFIIF effectively from all complexes downstream of the collapse
      transition, but this displacement is surprisingly slow: complete loss of TFIIF
      stimulation of elongation requires 5 min of incubation with Gdown1. The
      relatively slow functional loading of Gdown1 in the presence of TFIIF suggests
      that Gdown1 works in promoter-proximal pausing by locking in the paused state
      after elongation is already antagonized by other factors, including DSIF, NELF
      and possibly the first downstream nucleosome.

PMID- 27716822
TI  - Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2.
AB  - Chemerin is a small chemotactic protein originally identified as the natural
      ligand of CMKLR1. More recently, two other receptors, GPR1 and CCRL2, have been
      reported to bind chemerin but their functional relevance remains poorly
      understood. In this study, we compared the binding and signaling properties of
      the three human chemerin receptors and showed differences in mode of chemerin
      binding and receptor signaling. Chemerin binds to all three receptors with low
      nanomolar affinities. However, the contribution of the chemerin C-terminus to
      binding efficiency varies greatly amongst receptors. By using BRET-based
      biosensors monitoring the activation of various G proteins, we showed that
      binding of chemerin and the chemerin 9 nonapeptide (149YFPGQFAFS157) to CMKLR1
      activates the three Galphai subtypes (Galphai1, Galphai2 and Galphai3) and the
      two Galphao isoforms (Galphaoa and Galphaob) with potencies correlated to binding
      affinities. In contrast, no significant activation of G proteins was detected
      upon binding of chemerin to GPR1 or CCRL2. Binding of chemerin and the chemerin 9
      peptide also induced the recruitment of beta-arrestin1 and 2 to CMKLR1 and GPR1,
      though to various degree, but not to CCRL2. However, the propensity of chemerin 9
      to activate beta-arrestins relative to chemerin is higher when bound to GPR1.
      Finally, we showed that binding of chemerin to CMKLR1 and GPR1 promotes also the
      internalization of the two receptors and the phosphorylation of ERK1/2 MAP
      kinases, although with a different efficiency, and that phosphorylation of ERK1/2
      requires both Galphai/o and beta-arrestin2 activation but not beta-arrestin1.
      Collectively, these data support a model in which each chemerin receptor displays
      selective signaling properties.

PMID- 27716823
TI  - Influence of Rotational Nucleosome Positioning on Transcription Start Site
      Selection in Animal Promoters.
AB  - The recruitment of RNA-Pol-II to the transcription start site (TSS) is an
      important step in gene regulation in all organisms. Core promoter elements (CPE)
      are conserved sequence motifs that guide Pol-II to the TSS by interacting with
      specific transcription factors (TFs). However, only a minority of animal
      promoters contains CPEs. It is still unknown how Pol-II selects the TSS in their
      absence. Here we present a comparative analysis of promoters' sequence
      composition and chromatin architecture in five eukaryotic model organisms, which
      shows the presence of common and unique DNA-encoded features used to organize
      chromatin. Analysis of Pol-II initiation patterns uncovers that, in the absence
      of certain CPEs, there is a strong correlation between the spread of initiation
      and the intensity of the 10 bp periodic signal in the nearest downstream
      nucleosome. Moreover, promoters' primary and secondary initiation sites show a
      characteristic 10 bp periodicity in the absence of CPEs. We also show that DNA
      natural variants in the region immediately downstream the TSS are able to affect
      both the nucleosome-DNA affinity and Pol-II initiation pattern. These findings
      support the notion that, in addition to CPEs mediated selection, sequence-induced
      nucleosome positioning could be a common and conserved mechanism of TSS selection
      in animals.

PMID- 27716824
TI  - Changes in Drivers' Visual Performance during the Collision Avoidance Process as
      a Function of Different Field of Views at Intersections.
AB  - The intersection field of view (IFOV) indicates an extent that the visual
      information can be observed by drivers. It has been found that further enhancing
      IFOV can significantly improve emergent collision avoidance performance at
      intersections, such as faster brake reaction time, smaller deceleration rate, and
      lower traffic crash involvement risk. However, it is not known how IFOV affects
      drivers' eye movements, visual attention and the relationship between visual
      searching and traffic safety. In this study, a driving simulation experiment was
      conducted to uncover the changes in drivers' visual performance during the
      collision avoidance process as a function of different field of views at an
      intersection by using an eye tracking system. The experimental results showed
      that drivers' ability in identifying the potential hazard in terms of visual
      searching was significantly affected by different IFOV conditions. As the IFOVs
      increased, drivers had longer gaze duration (GD) and more number of gazes (NG) in
      the intersection surrounding areas and paid more visual attention to capture
      critical visual information on the emerging conflict vehicle, thus leading to a
      better collision avoidance performance and a lower crash risk. It was also found
      that female drivers had a better visual performance and a lower crash rate than
      male drivers. From the perspective of drivers' visual performance, the results
      strengthened the evidence that further increasing intersection sight distance
      standards should be encouraged for enhancing traffic safety.

PMID- 27716825
TI  - Neighborhood Characteristics and Cardiovascular Risk among Older People in Japan:
      Findings from the JAGES Project.
AB  - Previous studies have found an association between neighborhood characteristics
      (i.e., aspects of the physical and social environment) and the incidence of
      cardiovascular disease (CVD) and elevated CVD risk. This study investigated the
      relationship between neighborhood characteristics and CVD risk among older people
      in Japan where research on this association is scarce. Data came from the Japan
      Gerontological Evaluation Study project; questionnaire data collected from 3,810
      people aged 65 years or older living in 20 primary school districts in Aichi
      prefecture, Japan, was linked to a computed composite CVD risk score based on
      biomarker data (i.e., hemoglobin A1c, systolic blood pressure, diastolic blood
      pressure, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, and estimated glomerular filtration rate). A sex-stratified
      multilevel linear regression analysis revealed that for male participants, living
      in neighborhoods with a higher perceived occurrence of traffic accidents and
      reduced personal safety was associated with an elevated CVD risk (coefficient =
      1.08 per interquartile range increase, 95% confidence interval [CI] = 0.30 to
      1.86) whereas males living in neighborhoods with a higher perceived proximity of
      exercise facilities had a lower risk (coefficient = -1.00, 95% CI = -1.78 to 
      0.21). For females, there was no statistically significant association between
      neighborhood characteristics and CVD risk. This study suggests that aspects of
      the neighborhood environment might be important for CVD morbidity and mortality
      in Japan, particularly among men.

PMID- 27716826
TI  - Meteorin-Like Shows Unique Expression Pattern in Bone and Its Overexpression
      Inhibits Osteoblast Differentiation.
AB  - The present study was performed to identify and characterize genes involved in
      osteoblasts function. Firstly, we constructed and sequenced a human osteoblast
      full-length cDNA library to screen for genes whose functions have not been
      reported and further identify these candidate genes through detecting the
      relationship with the activator protein-1 (AP-1) transcription factor complex
      using a dual luciferase reporter system. Only one gene, namely METRNL (Meteorin,
      glial cell differentiation regulator-like) has been screened out. We performed
      immunohistochemistry to analyze expression patterns in bone and established a
      stable transfection MG63 cell line of METRNL-EGFP fusion protein overexpression
      to analyze the function of METRNL in mineralized nodule formation.
      Immunohistochemistry showed METRNL expression in hypertrophic chondrocytes and
      osteoblasts lining trabecular bone surfaces. Overexpression of METRNL inhibited
      mineralized nodule formation by the MG63 osteosarcoma cell line. Thus, the
      identified gene, METRNL, which is associated with AP-1 transcription factor
      complex activity, has a unique expression pattern in bone. In addition, the
      anomalous expression of METRNL may inhibit bone cell differentiation.

PMID- 27716827
TI  - Predictors of Treatment Failure among Adult Antiretroviral Treatment (ART)
      Clients in Bale Zone Hospitals, South Eastern Ethiopia.
AB  - BACKGROUND: Treatment failure defined as progression of disease after initiation
      of ART or when the anti-HIV medications can't control the infection. One of the
      major concerns over the rapid scaling up of ART is the emergence and transmission
      of HIV drug resistant strains at the population level due to treatment failure.
      This could lead to the failure of basic ART programs. Thus this study aimed to
      investigate the predictors of treatment failure among adult ART clients in Bale
      Zone Hospitals, South east Ethiopia. METHODS: Retrospective cohort study was
      employed in four hospitals of Bale zone named Goba, Robe, Ginir and Delomena. A
      total of 4,809 adult ART clients were included in the analysis from these four
      hospitals. Adherence was measured by pill count method. The Kaplan Meier (KM)
      curve was used to describe the survival time of ART patients without treatment
      failure. Bivariate and multivariable Cox proportional hazards regression models
      were used for identifying associated factors of treatment failure. RESULT: The
      incidence rate of treatment failure was found 9.38 (95% CI 7.79-11.30) per 1000
      person years. Male ART clients were more likely to experience treatment failure
      as compared to females [AHR = 4.49; 95% CI: (2.61-7.73)].Similarly, lower CD4
      count (<100 m3/dl) at initiation of ART was found significantly associated with
      higher odds of treatment failure [AHR = 3.79; 95% CI: (2.46-5.84).Bedridden [AHR
      = 5.02; 95% CI: (1.98-12.73)] and ambulatory [AHR = 2.12; 95% CI: (1.08-4.07)]
      patients were more likely to experience treatment failure as compared to patients
      with working functional status. TB co-infected clients had also higher odds to
      experience treatment failure [AHR = 3.06; 95% CI: (1.72-5.44)]. Those patients
      who had developed TB after ART initiation had higher odds to experience treatment
      failure as compared to their counter parts [AHR = 4.35; 95% CI: (1.99-9.54].
      Having other opportunistic infection during ART initiation was also associated
      with higher odds of experiencing treatment failure [AHR = 7.0, 95% CI: (3.19
      15.37)]. Similarly having fair [AHR = 4.99 95% CI: (1.90-13.13)] and poor drug
      adherence [AHR = 2.56; 95% CI: (1.12-5.86)]were significantly associated with
      higher odds of treatment failure as compared to clients with good adherence.
      CONCLUSION: The rate of treatment failure in Bale zone hospitals needs attention.
      Prevention and control of TB and other opportunistic infections, promotion of ART
      initiation at higher CD4 level, and better functional status, improving drug
      adherence are important interventions to reduce treatment failure among ART
      clients in Southeastern Ethiopia.

PMID- 27716828
TI  - Retrospective Parameter Estimation and Forecast of Respiratory Syncytial Virus in
      the United States.
AB  - Recent studies have shown that systems combining mathematical modeling and
      Bayesian inference methods can be used to generate real-time forecasts of future
      infectious disease incidence. Here we develop such a system to study and forecast
      respiratory syncytial virus (RSV). RSV is the most common cause of acute lower
      respiratory infection and bronchiolitis. Advanced warning of the epidemic timing
      and volume of RSV patient surges has the potential to reduce well-documented
      delays of treatment in emergency departments. We use a susceptible-infectious
      recovered (SIR) model in conjunction with an ensemble adjustment Kalman filter
      (EAKF) and ten years of regional U.S. specimen data provided by the Centers for
      Disease Control and Prevention. The data and EAKF are used to optimize the SIR
      model and i) estimate critical epidemiological parameters over the course of each
      outbreak and ii) generate retrospective forecasts. The basic reproductive number,
      R0, is estimated at 3.0 (standard deviation 0.6) across all seasons and
      locations. The peak magnitude of RSV outbreaks is forecast with nearly 70%
      accuracy (i.e. nearly 70% of forecasts within 25% of the actual peak), four weeks
      before the predicted peak. This work represents a first step in the development
      of a real-time RSV prediction system.

PMID- 27716829
TI  - Analysis of Microstructure of the Cardiac Conduction System Based on Three
      Dimensional Confocal Microscopy.
AB  - The specialised conducting tissues present in the ventricles are responsible for
      the fast distribution of the electrical impulse from the atrio-ventricular node
      to regions in the subendocardial myocardium. Characterisation of anatomical
      features of the specialised conducting tissues in the ventricles is highly
      challenging, in particular its most distal section, which is connected to the
      working myocardium via Purkinje-myocardial junctions. The goal of this work is to
      characterise the architecture of the distal section of the Purkinje network by
      differentiating Purkinje cells from surrounding tissue, performing a segmentation
      of Purkinje fibres at cellular scale, and mathematically describing its
      morphology and interconnections. Purkinje cells from rabbit hearts were
      visualised by confocal microscopy using wheat germ agglutinin labelling. A total
      of 16 3D stacks including labeled Purkinje cells were collected, and semi
      automatically segmented. State-of-the-art graph metrics were applied to estimate
      regional and global features of the Purkinje network complexity. Two types of
      cell types, tubular and star-like, were characterised from 3D segmentations. The
      analysis of 3D imaging data confirms the previously suggested presence of two
      types of Purkinje-myocardium connections, a 2D interconnection sheet and a funnel
      one, in which the narrow side of a Purkinje fibre connect progressively to muscle
      fibres. The complex network analysis of interconnected Purkinje cells showed no
      small-world connectivity or assortativity properties. These results might help
      building more realistic computational PK systems at high resolution levels
      including different cell configurations and shapes. Better knowledge on the
      organisation of the network might help in understanding the effects that several
      treatments such as radio-frequency ablation might have when the PK system is
      disrupted locally.

PMID- 27716831
TI  - Effects of Emotional Intelligence on the Impression of Irony Created by the
      Mismatch between Verbal and Nonverbal Cues.
AB  - Emotional information is conveyed through verbal and nonverbal signals, with
      nonverbal cues often being considered the decisive factor in the judgment of
      others' emotional states. The aim of the present study was to examine how verbal
      and nonverbal cues are integrated by perceivers. More specifically, we tested
      whether the mismatch between verbal and nonverbal information was perceived as an
      expression of irony. Moreover, we investigated the effects of emotional
      intelligence on the impression of irony. The findings revealed that the mismatch
      between verbal and nonverbal information created the impression of irony.
      Furthermore, participants higher in emotional intelligence were faster at rating
      such stimuli as ironic expressions.

PMID- 27716830
TI  - Oligodendrocyte Development in the Absence of Their Target Axons In Vivo.
AB  - Oligodendrocytes form myelin around axons of the central nervous system, enabling
      saltatory conduction. Recent work has established that axons can regulate certain
      aspects of oligodendrocyte development and myelination, yet remarkably
      oligodendrocytes in culture retain the ability to differentiate in the absence of
      axons and elaborate myelin sheaths around synthetic axon-like substrates. It
      remains unclear the extent to which the life-course of oligodendrocytes requires
      the presence of, or signals derived from axons in vivo. In particular, it is
      unclear whether the specific axons fated for myelination regulate the
      oligodendrocyte population in a living organism, and if so, which precise steps
      of oligodendrocyte-cell lineage progression are regulated by target axons. Here,
      we use live-imaging of zebrafish larvae carrying transgenic reporters that label
      oligodendrocyte-lineage cells to investigate which aspects of oligodendrocyte
      development, from specification to differentiation, are affected when we
      manipulate the target axonal environment. To drastically reduce the number of
      axons targeted for myelination, we use a previously identified kinesin-binding
      protein (kbp) mutant, in which the first myelinated axons in the spinal cord,
      reticulospinal axons, do not fully grow in length, creating a region in the
      posterior spinal cord where most initial targets for myelination are absent. We
      find that a 73% reduction of reticulospinal axon surface in the posterior spinal
      cord of kbp mutants results in a 27% reduction in the number of oligodendrocytes.
      By time-lapse analysis of transgenic OPC reporters, we find that the reduction in
      oligodendrocyte number is explained by a reduction in OPC proliferation and
      survival. Interestingly, OPC specification and migration are unaltered in the
      near absence of normal axonal targets. Finally, we find that timely
      differentiation of OPCs into oligodendrocytes does not depend at all on the
      presence of target axons. Together, our data illustrate the power of zebrafish
      for studying the entire life-course of the oligodendrocyte lineage in vivo in an
      altered axonal environment.

PMID- 27716832
TI  - Introduction of High Throughput Magnetic Resonance T2-Weighted Image Texture
      Analysis for WHO Grade 2 and 3 Gliomas.
AB  - Reports have suggested that tumor textures presented on T2-weighted images
      correlate with the genetic status of glioma. Therefore, development of an image
      analyzing framework that is capable of objective and high throughput image
      texture analysis for large scale image data collection is needed. The current
      study aimed to address the development of such a framework by introducing two
      novel parameters for image textures on T2-weighted images, i.e., Shannon entropy
      and Prewitt filtering. Twenty-two WHO grade 2 and 28 grade 3 glioma patients were
      collected whose pre-surgical MRI and IDH1 mutation status were available.
      Heterogeneous lesions showed statistically higher Shannon entropy than homogenous
      lesions (p = 0.006) and ROC curve analysis proved that Shannon entropy on T2WI
      was a reliable indicator for discrimination of homogenous and heterogeneous
      lesions (p = 0.015, AUC = 0.73). Lesions with well-defined borders exhibited
      statistically higher Edge mean and Edge median values using Prewitt filtering
      than those with vague lesion borders (p = 0.0003 and p = 0.0005 respectively).
      ROC curve analysis also proved that both Edge mean and median values were
      promising indicators for discrimination of lesions with vague and well defined
      borders and both Edge mean and median values performed in a comparable manner (p
      = 0.0002, AUC = 0.81 and p < 0.0001, AUC = 0.83, respectively). Finally, IDH1
      wild type gliomas showed statistically lower Shannon entropy on T2WI than IDH1
      mutated gliomas (p = 0.007) but no difference was observed between IDH1 wild type
      and mutated gliomas in Edge median values using Prewitt filtering. The current
      study introduced two image metrics that reflect lesion texture described on T2WI.
      These two metrics were validated by readings of a neuro-radiologist who was
      blinded to the results. This observation will facilitate further use of this
      technique in future large scale image analysis of glioma.

PMID- 27716833
TI  - Can You Judge a Disease Host by the Company It Keeps? Predicting Disease Hosts
      and Their Relative Importance: A Case Study for Leishmaniasis.
AB  - Zoonoses are an important class of infectious diseases. An important element
      determining the impact of a zoonosis on domestic animal and human health is host
      range. Although for particular zoonoses some host species have been identified,
      until recently there have been no methods to predict those species most likely to
      be hosts or their relative importance. Complex inference networks infer potential
      biotic interactions between species using their degree of geographic co
      occurrence, and have been posited as a potential tool for predicting disease
      hosts. Here we present the results of an interdisciplinary, empirical study to
      validate a model based on such networks for predicting hosts of Leishmania (L.)
      mexicana in Mexico. Using systematic sampling to validate the model predictions
      we identified 22 new species of host (34% of all species collected) with the
      probability to be a host strongly dependent on the probability of co-occurrence
      of vector and host. The results confirm that Leishmania (L.) mexicana is a
      generalist parasite but with a much wider host range than was previously thought.
      These results substantially change the geographic risk profile for Leishmaniasis
      and provide insights for the design of more efficient surveillance measures and a
      better understanding of potential dispersal scenarios.

PMID- 27716834
TI  - Round Spermatid Injection Rescues Female Lethality of a Paternally Inherited Xist
      Deletion in Mouse.
AB  - In mouse female preimplantation embryos, the paternal X chromosome (Xp) is
      silenced by imprinted X chromosome inactivation (iXCI). This requires production
      of the noncoding Xist RNA in cis, from the Xp. The Xist locus on the maternally
      inherited X chromosome (Xm) is refractory to activation due to the presence of an
      imprint. Paternal inheritance of an Xist deletion (XpDeltaXist) is embryonic
      lethal to female embryos, due to iXCI abolishment. Here, we circumvented the
      histone-to-protamine and protamine-to-histone transitions of the paternal genome,
      by fertilization of oocytes via injection of round spermatids (ROSI). This did
      not affect initiation of XCI in wild type female embryos. Surprisingly, ROSI
      using DeltaXist round spermatids allowed survival of female embryos. This was
      accompanied by activation of the intact maternal Xist gene, initiated with
      delayed kinetics, around the morula stage, resulting in Xm silencing. Maternal
      Xist gene activation was not observed in ROSI-derived males. In addition, no Xist
      expression was detected in male and female morulas that developed from oocytes
      fertilized with mature DeltaXist sperm. Finally, the expression of the X-encoded
      XCI-activator RNF12 was enhanced in both male (wild type) and female (wild type
      as well as XpDeltaXist) ROSI derived embryos, compared to in vivo fertilized
      embryos. Thus, high RNF12 levels may contribute to the specific activation of
      maternal Xist in XpDeltaXist female ROSI embryos, but upregulation of additional
      Xp derived factors and/or the specific epigenetic constitution of the round
      spermatid-derived Xp are expected to be more critical. These results illustrate
      the profound impact of a dysregulated paternal epigenome on embryo development,
      and we propose that mouse ROSI can be used as a model to study the effects of
      intergenerational inheritance of epigenetic marks.

PMID- 27716836
TI  - Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized
      One-Class Collaborative Filtering and Its Application to Drug Repurposing.
AB  - Target-based screening is one of the major approaches in drug discovery. Besides
      the intended target, unexpected drug off-target interactions often occur, and
      many of them have not been recognized and characterized. The off-target
      interactions can be responsible for either therapeutic or side effects. Thus,
      identifying the genome-wide off-targets of lead compounds or existing drugs will
      be critical for designing effective and safe drugs, and providing new
      opportunities for drug repurposing. Although many computational methods have been
      developed to predict drug-target interactions, they are either less accurate than
      the one that we are proposing here or computationally too intensive, thereby
      limiting their capability for large-scale off-target identification. In addition,
      the performances of most machine learning based algorithms have been mainly
      evaluated to predict off-target interactions in the same gene family for hundreds
      of chemicals. It is not clear how these algorithms perform in terms of detecting
      off-targets across gene families on a proteome scale. Here, we are presenting a
      fast and accurate off-target prediction method, REMAP, which is based on a dual
      regularized one-class collaborative filtering algorithm, to explore continuous
      chemical space, protein space, and their interactome on a large scale. When
      tested in a reliable, extensive, and cross-gene family benchmark, REMAP
      outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable.
      It can screen a dataset of 200 thousands chemicals against 20 thousands proteins
      within 2 hours. Using the reconstructed genome-wide target profile as the
      fingerprint of a chemical compound, we predicted that seven FDA-approved drugs
      can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six
      of them is supported by experimental evidences. Thus, REMAP is a valuable
      addition to the existing in silico toolbox for drug target identification, drug
      repurposing, phenotypic screening, and side effect prediction. The software and
      benchmark are available at https://github.com/hansaimlim/REMAP.

PMID- 27716835
TI  - Naringin Decreases TNF-alpha and HMGB1 Release from LPS-Stimulated Macrophages
      and Improves Survival in a CLP-Induced Sepsis Mice.
AB  - Naringin, a flavanone glycoside extracted from various plants, has a wide range
      of pharmacological effects. In the present study, we investigated naringin's
      mechanism of action and its inhibitory effect on lipopolysaccharide-induced tumor
      necrosis factor-alpha and high-mobility group box 1 expression in macrophages,
      and on death in a cecal ligation and puncture induced mouse model of sepsis.
      Naringin increased heme oxygenase 1 expression in peritoneal macrophage cells
      through the activation of adenosine monophosphate-activated protein kinase, p38,
      and NF-E2-related factor 2. Inhibition of heme oxygenase 1 abrogated the
      naringin's inhibitory effect on high-mobility group box 1 expression and NF-kB
      activation in lipopolysaccharide-stimulated macrophages. Moreover, mice
      pretreated with naringin (200 mg/kg) exhibited decreased sepsis-induced mortality
      and lung injury, and alleviated lung pathological changes. However, the
      naringin's protective effects on sepsis-induced lung injury were eliminated by
      zinc protoporphyrin, a heme oxygenase 1 competitive inhibitor. These results
      revealed the mechanism underlying naringin's protective effect in inflammation
      and may be beneficial for the treatment of sepsis.

PMID- 27716837
TI  - Optical Coherence Tomography in the UK Biobank Study - Rapid Automated Analysis
      of Retinal Thickness for Large Population-Based Studies.
AB  - PURPOSE: To describe an approach to the use of optical coherence tomography (OCT)
      imaging in large, population-based studies, including methods for OCT image
      acquisition, storage, and the remote, rapid, automated analysis of retinal
      thickness. METHODS: In UK Biobank, OCT images were acquired between 2009 and 2010
      using a commercially available "spectral domain" OCT device (3D OCT-1000,
      Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area,
      and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers
      in a central repository, adjacent to high performance computers. Rapid, automated
      analysis of retinal thickness was performed using custom image segmentation
      software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL).
      This software employs dual-scale gradient information to allow for automated
      segmentation of nine intraretinal boundaries in a rapid fashion. RESULTS: 67,321
      participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as
      part of the ocular module. 134,611 images were successfully processed with 31
      images failing segmentation analysis due to corrupted OCT files or withdrawal of
      subject consent for UKBB study participation. Average time taken to call up an
      image from the database and complete segmentation analysis was approximately 120
      seconds per data set per login, and analysis of the entire dataset was completed
      in approximately 28 days. CONCLUSIONS: We report an approach to the rapid,
      automated measurement of retinal thickness from nearly 140,000 OCT image sets
      from the UK Biobank. In the near future, these measurements will be publically
      available for utilization by researchers around the world, and thus for
      correlation with the wealth of other data collected in UK Biobank. The automated
      analysis approaches we describe may be of utility for future large population
      based epidemiological studies, clinical trials, and screening programs that
      employ OCT imaging.

PMID- 27716838
TI  - Heteroresistant Vancomycin Intermediate Coagulase Negative Staphylococcus in the
      NICU: A Systematic Review.
AB  - CONTEXT: NICUs in the province of Quebec have seen an increase in hVICoNS,
      detected in the clinical laboratory. OBJECTIVE: To investigate the clinical
      relevance of hVICoNS on the course of infection, and to determine the prevalence
      of hVICoNS sepsis in the NICU. METHODS: We searched MEDLINE, EMBASE, and PubMed
      from 1 January 1980 to 1 July 2016. Both observational and interventional studies
      were considered eligible if they provided data on hVICoNS in the NICU population.
      Two investigators independently reviewed studies for data extraction. Data
      extracted included: number of CoNS cultures, prevalence of hVICoNS, and clonality
      of strains. RESULTS: Of the 613 studies identified, 19 studies were reviewed, and
      5 studies included in the final review. No studies addressed the clinical
      significance of hVICoNS in the NICU. The prevalence of hVICoNS in the NICU varied
      greatly, ranging from 2.3% to 100%. LIMITATIONS: Publication bias could not be
      assessed, and risk of bias in some of the included studies due to small sample
      size and poor methods reporting. The quality of all included studies was low
      according to GRADE criteria, and the inclusion criteria restricted to either
      English or French studies. CONCLUSIONS: Our review suggests that heteroresistance
      to vancomycin is much more common than previously believed. Our search however
      did not identify any studies that explicitly assessed any clinical implications
      of hVICoNS infections, thereby highlighting the need for research to assess the
      true impact of hVICoNS infection and to determine its significance on patient
      mortality and morbidity in the NICU.

PMID- 27716839
TI  - Differences in Proinflammatory Property of Six Subtypes of Peroxiredoxins and
      Anti-Inflammatory Effect of Ligustilide in Macrophages.
AB  - BACKGROUND: Peroxiredoxins (Prxs) are proposed to function as damage-associated
      molecular patterns (DAMPs) and contribute to post-ischemic neuroinflammation and
      brain injury by activating Toll-like receptor (TLR) 4 at the acute and subacute
      phases after ischemic stroke. However, there are few studies concerning the
      inflammatory profiles of six distinct subtypes of Prxs (Prx1-Prx6). Our previous
      study demonstrated that the protective effect of ligustilide (LIG) against
      cerebral ischemia was associated with inhibition of neuroinflammatory response
      and Prx/TLR4 signaling in rats. Herein, the present study explored the
      inflammatory members of Prxs and the effect of LIG on their inflammatory
      responses in macrophages. METHODOLOGY/PRINCIPAL FINDINGS: The murine RAW264.7
      macrophages were treated with each of exogenous recombinant Prxs at a range of 1
      to 50 nM for 24 h. The WST-1 test showed that Prx3 exhibited a significant
      cytotoxicity, whereas the rest five Prxs did not affect cellular viability. The
      quantitative measurements with spectrometry or ELISA indicated that three
      subtypes, Prx1, Prx2 and Prx4, increased production of proinflammatory mediators,
      including nitric oxide (NO) metabolites, tumor necrosis factor-alpha (TNF-alpha),
      and interleukin-6 (IL-6) in a concentration-dependent manner. Immunostaining
      demonstrated that 20 nM Prx1, Prx2 or Prx4 significantly increased expression of
      TLR4 and iNOS and nuclear translocation of NF-kappaB p65. However, Prx5 and Prx6
      showed no poinflammatory effect in macrophages. Remarkably, LIG treatment
      effectively inhibited the inflammatory response induced by Prx1, Prx2 and Prx4.
      CONCLUSION: Three members of Prxs, Prx1, Prx2 and Prx4, are inflammatory DAMPs
      that induce TLR4 activation and inflammatory response in macrophages, which is
      effectively inhibited by LIG. These results suggest that inflammatory Prxs
      activated macrophages may provide a novel cellular model for screening the
      potential inhibitors of DAMPs-associated inflammatory diseases such as stroke.
      Moreover, selective blocking strategies targeting the inflammatory subtypes of
      Prxs probably provide promising therapeutic approaches with a prolonged time
      window for stroke.

PMID- 27716840
TI  - Cadherin-2 Is Required Cell Autonomously for Collective Migration of Facial
      Branchiomotor Neurons.
AB  - Collective migration depends on cell-cell interactions between neighbors that
      contribute to their overall directionality, yet the mechanisms that control the
      coordinated migration of neurons remains to be elucidated. During hindbrain
      development, facial branchiomotor neurons (FBMNs) undergo a stereotypic
      tangential caudal migration from their place of birth in rhombomere (r)4 to their
      final location in r6/7. FBMNs engage in collective cell migration that depends on
      neuron-to-neuron interactions to facilitate caudal directionality. Here, we
      demonstrate that Cadherin-2-mediated neuron-to-neuron adhesion is necessary for
      directional and collective migration of FBMNs. We generated stable transgenic
      zebrafish expressing dominant-negative Cadherin-2 (Cdh2DeltaEC) driven by the
      islet1 promoter. Cell-autonomous inactivation of Cadherin-2 function led to non
      directional migration of FBMNs and a defect in caudal tangential migration.
      Additionally, mosaic analysis revealed that Cdh2DeltaEC-expressing FBMNs are not
      influenced to migrate caudally by neighboring wild-type FBMNs due to a defect in
      collective cell migration. Taken together, our data suggest that Cadherin-2 plays
      an essential cell-autonomous role in mediating the collective migration of FBMNs.

PMID- 27716841
TI  - Trajectories of Risk for Specific Readmission Diagnoses after Hospitalization for
      Heart Failure, Acute Myocardial Infarction, or Pneumonia.
AB  - BACKGROUND: The risk of rehospitalization is elevated in the immediate post
      discharge period and declines over time. It is not known if the extent and timing
      of risk vary across readmission diagnoses, suggesting that recovery and
      vulnerability after discharge differ by physiologic system. OBJECTIVE: We
      compared risk trajectories for major readmission diagnoses in the year after
      discharge among all Medicare fee-for-service beneficiaries hospitalized with
      heart failure (HF), acute myocardial infarction (AMI), or pneumonia from 2008
      2010. METHODS: We estimated the daily risk of rehospitalization for 12 major
      readmission diagnostic categories after accounting for the competing risk of
      death after discharge. For each diagnostic category, we identified (1) the time
      required for readmission risk to peak and then decline 50% from maximum values
      after discharge; (2) the time required for readmission risk to approach plateau
      periods of minimal day-to-day change; and (3) the extent to which hospitalization
      risks are higher among patients recently discharged from the hospital compared
      with the general elderly population. RESULTS: Among >3,000,000 hospitalizations,
      the yearly rate of rehospitalization was 67.0%, 49.5%, and 55.3% after
      hospitalization for HF, AMI, and pneumonia, respectively. The extent and timing
      of risk varied by readmission diagnosis and initial admitting condition. Risk of
      readmission for gastrointestinal bleeding/anemia peaked particularly late after
      hospital discharge, occurring 10, 6, and 7 days after hospitalization for HF,
      AMI, and pneumonia, respectively. Risk of readmission for trauma/injury declined
      particularly slowly, requiring 38, 20, and 38 days to decline by 50% after
      hospitalization for HF, AMI, and pneumonia, respectively. CONCLUSIONS: Patterns
      of vulnerability to different conditions that cause rehospitalization vary by
      time after hospital discharge. This finding suggests that recovery of various
      physiologic systems occurs at different rates and that post-discharge
      interventions to minimize vulnerability to specific conditions should be tailored
      to their underlying risks.

PMID- 27716842
TI  - Effect of Preoperative Risk Group Stratification on Oncologic Outcomes of
      Patients with Adverse Pathologic Findings at Radical Prostatectomy.
AB  - BACKGROUND: Current National Comprehensive Cancer Network guidelines recommend
      postoperative radiation therapy based only on adverse pathologic findings (APFs),
      irrespective of preoperative risk group. We assessed whether a model
      incorporating both the preoperative risk group and APFs could predict long-term
      oncologic outcomes better than a model based on APFs alone. METHODS: We
      retrospectively reviewed 4,404 men who underwent radical prostatectomy (RP) at
      our institution between 1992 and 2014. After excluding patients receiving
      neoadjuvant therapy or with incomplete pathological or follow-up data, 3,092 men
      were included in the final analysis. APFs were defined as extraprostatic
      extension (EPE), seminal vesicle invasion (SVI), or a positive surgical margin
      (PSM). The adequacy of model fit to the data was compared using the likelihood
      ratio test between the models with and without risk groups, and model
      discrimination was compared with the concordance index (c-index) for predicting
      biochemical recurrence (BCR) and prostate cancer-specific mortality (PCSM). We
      performed multivariate Cox proportional hazard model and competing risk
      regression analyses to identify predictors of BCR and PCSM in the total patient
      group and each of the risk groups. RESULTS: Adding risk groups to the model
      containing only APFs significantly improved the fit to the data (likelihood-ratio
      test, p <0.001) and the c-index increased from 0.693 to 0.732 for BCR and from
      0.707 to 0.747 for PCSM. A RP Gleason score (GS) >=8 and a PSM were independently
      associated with BCR in the total patient group and also each risk group. However,
      only a GS >=8 and SVI were associated with PCSM in the total patient group (GS
      >=8: hazard ratio [HR] 5.39 and SVI: HR 3.36) and the high-risk group (GS >=8: HR
      6.31 and SVI: HR 4.05). CONCLUSION: The postoperative estimation of oncologic
      outcomes in men with APFs at RP was improved by considering preoperative risk
      group stratification. Although a PSM was an independent predictor for BCR, only a
      RP GS >=8 and SVI were associated with PCSM in the total patient and high-risk
      groups.

PMID- 27716843
TI  - Long-Term Durability of Tenofovir-Based Antiretroviral Therapy in Relation to the
      Co-Administration of Other Drug Classes in Routine Clinical Practice.
AB  - BACKGROUND: In clinical trials, toxicity leading to tenofovir disoproxil fumarate
      (TDF) discontinuation is rare (3% by 2 years); however in clinical practice it
      seems to be higher, particularly when TDF is co-administered with ritonavir
      boosted protease inhibitors (PI/r). Aims of this study were to assess the rate of
      TDF discontinuations in clinical practice and to identify factors associated with
      the risk of stopping TDF. METHODS: All antiretroviral treatment (ART)-naive
      patients initiating a TDF-based regimen were selected from the ICONA Foundation
      Study cohort. The primary outcome was TDF discontinuation regardless of the
      reason; secondary outcome measures were TDF discontinuation due to toxicity and
      selective TDF discontinuation (that is, TDF discontinuation or substitution,
      maintaining unchanged the remaining antiretroviral treatment). RESULTS: 3,618 ART
      naive patients were included: 54% started a PI/r-based and 46% a NNRTI-based
      based regimen. Two-hundred-seventy-seven patients discontinued TDF and
      reintroduced ART within 30 days without TDF. The probability of TDF
      discontinuation regardless of the reason was of 7.4% (95%CI:6.4-8.5) by 2 years
      and 14.1% (95%CI:12.2-16.1) by 5 years. The 5-year KM estimates in the PI/r vs.
      NNRTI group were 20.4% vs. 7.6%, respectively (log-rank p = 0.0001), for the
      outcome of stopping regardless of the reason, and 10.7% vs. 4.7% (p = 0.0001) for
      discontinuation due to toxicity. PI/r use and lower eGFR were associated with an
      increased risk of discontinuing TDF. CONCLUSION: In our cohort, the frequency of
      TDF discontinuations was higher than that observed in clinical trials. Co
      administration of TDF with PI/r was associated with an increased rate of TDF
      discontinuations. Further studies are needed to clarify the mechanisms that might
      have led to this outcome.

PMID- 27716845
TI  - Yolked Oocyte Dynamics Support Agreement between Determinate- and Indeterminate
      Method Estimates of Annual Fecundity for a Northeastern United States Population
      of American Shad.
AB  - Reports of American shad fecundity identify two important themes regarding egg
      production in fishes. First, geographic variation occurs and is biologically
      meaningful. Shad annual fecundity decreases with increasing latitude, but
      predicted lifetime fecundity does not, because of a counter-gradient of survival
      probability, all of which can explain the adaptive significance of natal homing.
      Second, the appropriate method of measuring fecundity depends on the pattern of
      oocyte development. Historically, the relatively simple determinate-fecundity
      method was used; however, a recent study in a Virginia river indicates that this
      method may be biased, requiring the more complicated indeterminate method. We
      address both themes with collections from the 2015 shad spawning run in the
      Connecticut River, USA. Criteria for using a determinate method were satisfied
      for this northern population: 1) a size gap evident in the oocyte size frequency
      distribution, indicating group-synchronous development of yolked oocytes; 2) a
      decline, early in spawning, in the standing stock of yolked oocytes; and 3) low
      levels of atresia at the end of spawning. The determinate-method estimate of
      American shad annual (2015) fecundity (303,000 +/- 73,400; mean +/- sd)
      overlapped historic estimates for this and a neighboring river. The indeterminate
      method estimate of annual (2015) fecundity (311,500 +/- 4,500 sd) was not
      significantly different from the determinate-method estimate (Student's t-test, P
      > 0.05). In contrast, indeterminate-method estimates of annual fecundity for a
      Virginia population were twice as high as that measured by the determinate method
      in the past. This can all be explained by fundamentally different patterns of
      oogenesis (i.e., group synchrony versus asynchrony with respect to yolk
      development) at different latitudes. American shad, which is distributed within
      its native range from the Canadian maritimes to Florida, USA (50-30 degrees N),
      may be particularly well suited to evaluate intra-specific variation in oocyte
      development, a relatively unexplored life history trait.

PMID- 27716844
TI  - SARAH Domain-Mediated MST2-RASSF Dimeric Interactions.
AB  - RASSF enzymes act as key apoptosis activators and tumor suppressors, being
      downregulated in many human cancers, although their exact regulatory roles remain
      unknown. A key downstream event in the RASSF pathway is the regulation of MST
      kinases, which are main effectors of RASSF-induced apoptosis. The regulation of
      MST1/2 includes both homo- and heterodimerization, mediated by helical SARAH
      domains, though the underlying molecular interaction mechanism is unclear. Here,
      we study the interactions between RASSF1A, RASSF5, and MST2 SARAH domains by
      using both atomistic molecular simulation techniques and experiments. We
      construct and study models of MST2 homodimers and MST2-RASSF SARAH heterodimers,
      and we identify the factors that control their high molecular stability. In
      addition, we also analyze both computationally and experimentally the
      interactions of MST2 SARAH domains with a series of synthetic peptides
      particularly designed to bind to it, and hope that our approach can be used to
      address some of the challenging problems in designing new anti-cancer drugs.

PMID- 27716846
TI  - Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute
      Nephrotoxicity.
AB  - Aristolochia manshuriensis Kom (AMK) is a member of the Aristolochiaceae family
      and is a well-known cause of aristolochic acid (AA) nephropathy. In this study,
      we investigated the potential of omeprazole (OM) to alleviate AMK-induced
      nephrotoxicity. We found that OM reduced mouse mortality caused by AMK and
      attenuated AMK-induced acute nephrotoxicity in rats. OM enhanced hepatic Cyp
      1a1/2 and renal Cyp 1a1 expression in rats, as well as CYP 1A1 expression in
      human renal tubular epithelial cells (HKCs). HKCs with ectopic CYP 1A1 expression
      were more tolerant to AA than the control cells. Therefore, OM may alleviate AMK
      mediated acute nephrotoxicity through induction of CYP 1A1. We suggest that the
      coadministration of OM might be beneficial for reducing of AA-induced
      nephrotoxicity.

PMID- 27716847
TI  - Lowered Expression of Tumor Suppressor Candidate MYO1C Stimulates Cell
      Proliferation, Suppresses Cell Adhesion and Activates AKT.
AB  - Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of
      recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2,
      the substrate of Phosphoinositide 3-kinase (PI3K), and to Rictor, suggesting a
      role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C
      expression status in a panel of well-stratified endometrial carcinomas as well as
      to assess the biological significance of MYO1C as a tumor suppressor in vitro. We
      found a significant correlation between the tumor stage and lowered expression of
      MYO1C in endometrial carcinoma samples. In cell transfection experiments, we
      found a negative correlation between MYO1C expression and cell proliferation, and
      MYO1C silencing resulted in diminished cell migration and adhesion. Cells
      expressing excess of MYO1C had low basal level of phosphorylated protein kinase B
      (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker
      phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken
      together the present study gives further evidence for tumor suppressor activity
      of MYO1C and suggests MYO1C mediates its tumor suppressor function through
      inhibition of PI3K pathway and its involvement in loss of contact inhibition.

PMID- 27716848
TI  - Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and
      Ex Vivo HIV Infection.
AB  - During chronic HIV infection, viral replication is concentrated in secondary
      lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in
      extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8
      T cells are a regulatory subset differing from conventional CD8 T cells, and
      constitute the majority of CD8 T cells in the follicle. This subset, CD8
      follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit
      enhanced expression of Tim-3 and IL-10, and express less perforin compared to
      conventional CD8 T cells. CD8 TFR modestly limit HIV replication in follicular
      helper T cells (TFH), impair TFH IL-21 production via Tim-3, and inhibit IgG
      production by B cells during ex vivo HIV infection. CD8 TFR induce TFH apoptosis
      through HLA-E, but induce less apoptosis than conventional CD8 T cells. These
      data demonstrate that a unique regulatory CD8 population exists in follicles that
      impairs GC function in HIV infection.

PMID- 27716849
TI  - Increased CD40 Expression Enhances Early STING-Mediated Type I Interferon
      Response and Host Survival in a Rodent Malaria Model.
AB  - Both type I interferon (IFN-I) and CD40 play a significant role in various
      infectious diseases, including malaria and autoimmune disorders. CD40 is mostly
      known to function in adaptive immunity, but previous observations of elevated
      CD40 levels early after malaria infection of mice led us to investigate its roles
      in innate IFN-I responses and disease control. Using a Plasmodium yoelii
      nigeriensis N67 and C57BL/6 mouse model, we showed that infected CD40-/- mice had
      reduced STING and serum IFN-beta levels day-2 post infection, higher day-4
      parasitemia, and earlier deaths. CD40 could greatly enhance STING-stimulated
      luciferase signals driven by the IFN-beta promoter in vitro, which was mediated
      by increased STING protein levels. The ability of CD40 to influence STING
      expression was confirmed in CD40-/- mice after malaria infection. Substitutions
      at CD40 TRAF binding domains significantly decreased the IFN-beta signals and
      STING protein level, which was likely mediated by changes in STING ubiquitination
      and degradation. Increased levels of CD40, STING, and ISRE driven luciferase
      signal in RAW Lucia were observed after phagocytosis of N67-infected red blood
      cells (iRBCs), stimulation with parasite DNA/RNA, or with selected TLR ligands
      [LPS, poly(I:C), and Pam3CSK4]. The results suggest stimulation of CD40
      expression by parasite materials through TLR signaling pathways, which was
      further confirmed in bone marrow derived dendritic cells/macrophages
      (BMDCs/BMDMs) and splenic DCs from CD40-/-, TLR3-/- TLR4-/-, TRIF-/-, and MyD88-/
      mice after iRBC stimulation or parasite infection. Our data connect several
      signaling pathways consisting of phagocytosis of iRBCs, recognition of parasite
      DNA/RNA (possibly GPI) by TLRs, elevated levels of CD40 and STING proteins,
      increased IFN-I production, and longer host survival time. This study reveals
      previously unrecognized CD40 function in innate IFN-I responses and protective
      pathways in infections with malaria strains that induce a strong IFN-I response,
      which may provide important information for better understanding and management
      of malaria.

PMID- 27716851
TI  - Mapping the Geometric Evolution of Protein Folding Motor.
AB  - Polypeptide chain has an invariant main-chain and a variant side-chain sequence.
      How the side-chain sequence determines fold in terms of its chemical constitution
      has been scrutinized extensively and verified periodically. However, a focussed
      investigation on the directive effect of side-chain geometry may provide
      important insights supplementing existing algorithms in mapping the geometrical
      evolution of protein chains and its structural preferences. Geometrically,
      folding of protein structure may be envisaged as the evolution of its geometric
      variables: phi, and psi dihedral angles of polypeptide main-chain directed by
      chi1, and chi2 of side chain. In this work, protein molecule is metaphorically
      modelled as a machine with 4 rotors phi, psi, chi1 and chi2, with its evolution
      to the functional fold is directed by combinations of its rotor directions. We
      observe that differential rotor motions lead to different secondary structure
      formations and the combinatorial pattern is unique and consistent for particular
      secondary structure type. Further, we found that combination of rotor geometries
      of each amino acid is unique which partly explains how different amino acid
      sequence combinations have unique structural evolution and functional adaptation.
      Quantification of these amino acid rotor preferences, resulted in the generation
      of 3 substitution matrices, which later on plugged in the BLAST tool, for
      evaluating their efficiency in aligning sequences. We have employed BLOSUM62 and
      PAM30 as standard for primary evaluation. Generation of substitution matrices is
      a logical extension of the conceptual framework we attempted to build during the
      development of this work. Optimization of matrices following the conventional
      routines and possible application with biologically relevant data sets are beyond
      the scope of this manuscript, though it is a part of the larger project design.

PMID- 27716850
TI  - Efficient Killing of High Risk Neuroblastoma Using Natural Killer Cells Activated
      by Plasmacytoid Dendritic Cells.
AB  - High-risk neuroblastoma (NB) remains a major therapeutic challenge despite the
      recent advent of disialoganglioside (GD2)-antibody treatment combined with
      interleukin (IL)-2 and granulocyte monocyte-colony stimulating factor (GM-CSF).
      Indeed, more than one third of the patients still die from this disease. Here, we
      developed a novel approach to improve the current anti-GD2 immunotherapy based on
      NK cell stimulation using toll-like receptor (TLR)-activated plasmacytoid
      dendritic cells (pDCs). We demonstrated that this strategy led to the efficient
      killing of NB cells. When the expression of GD2 was heterogeneous on NB cells,
      the combination of pDC-mediated NK-cell activation and anti-GD2 treatment
      significantly increased the cytotoxicity of NK cells against NB cells. Activation
      by pDCs led to a unique NK-cell phenotype characterized by increased surface
      expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),
      with increased expression of CD69 on CD56dim cytotoxic cells, and strong
      interferon-gamma production. Additionally, NB-cell killing was mediated by the
      TRAIL death-receptor pathway, as well as by the release of cytolytic granules via
      the DNAX accessory molecule 1 pathway. NK-cell activation and lytic activity
      against NB was independent of cell contact, depended upon type I IFN produced by
      TLR-9-activated pDCs, but was not reproduced by IFN-alpha stimulation alone.
      Collectively, these results highlighted the therapeutic potential of activated
      pDCs for patients with high-risk NB.

PMID- 27716852
TI  - Effects of Isaria fumosorosea on TYLCV (Tomato Yellow Leaf Curl Virus)
      Accumulation and Transmitting Capacity of Bemisia tabaci.
AB  - Tomato yellow leaf curl virus (TYLCV) is transmitted by the Bemisia tabaci pest
      Middle East-Asia Minor 1 (MEAM1) in China. Isaria fumosorosea is a fungal
      pathogen of B. tabaci. However, the effects of fungal infection on TYLCV
      expression and transmission by MEAM1 are unclear. In this study, potted tomatoes
      containing second instar nymphs of MEAM1 were treated with I. fumosorosea IfB01
      strain and the relationship between fungal infection in MEAM1 and its TYLCV
      transmission capacity was investigated. The results indicated that a
      significantly (p < 0.05) decreased incidence of transmission of TYLCV-infected
      plants (ITYPs) transmitted by second instar nymphs of MEAM1 infected with fungus.
      Further, we found a negative correlation between fungal conidial concentrations
      and eclosion rates of MEAM1, and a positive correlation between ITYPs and
      eclosion. In addition, when each plant was exposed to three adults treated with
      fungus, a significantly decreased transmission of TYLCV (TYTE) was observed in
      the infected group. However, the incidence of TYLCV-carrying MEAM1 adults (ITYAs)
      was not significantly different in the infected and control groups (p < 0.05).
      Nevertheless, a significant decrease in viral accumulation using TYLCV AC2 gene
      as a marker was observed in the fungus-infected MEAM1. In conclusion, the results
      suggested that I. fumosorosea infection decreases TYLCV accumulation in MEAM1 and
      subsequently reduces its transmission. Our study provides new insights into the
      relationship between host plant, plant virus, insect vector, and entomopathogenic
      fungus.

PMID- 27716853
TI  - Evaluation of the diagnostic potential of ex vivo Raman spectroscopy in gastric
      cancers: fingerprint versus high wavenumber.
AB  - The aim of this study was to apply Raman spectroscopy in the high wavenumber (HW)
      region (2800 to 3000??cm?1) for ex vivo detection of gastric cancer and compare
      its diagnostic potential with that of the fingerprint (FP) region (800 to
      1800??cm?1). Raman spectra were collected in the FP and HW regions to
      differentiate between normal mucosa (n=38) and gastric cancer (n=37). The
      distinctive Raman spectral differences between normal and cancer tissues are
      observed at 853, 879, 1157, 1319, 1338, 1448, and 2932??cm?1 and are primarily
      related to proteins, lipids, nucleic acids, collagen, and carotenoids in the
      tissue. In FP and HW Raman spectroscopy for diagnosis of gastric cancer,
      multivariate diagnostic algorithms based on partial-least-squares discriminant
      analysis, together with leave-one-sample-out cross validation, yielded diagnostic
      sensitivities of 94.59% and 81.08%, and specificities of 86.84% and 71.05%,
      respectively. Receiver operating characteristic analysis further confirmed that
      the FP region model performance is superior to that of the HW region model.
      Better differentiation between normal and gastric cancer tissues can be achieved
      using FP Raman spectroscopy and PLS-DA techniques, but the complementary natures
      of the FP and HW regions make both of them useful in diagnosis of gastric cancer.

PMID- 27716854
TI  - Comparison of Videostroboscopy to Stroboscopy Derived From High-Speed
      Videoendoscopy for Evaluating Patients With Vocal Fold Mass Lesions.
AB  - Purpose: Videostroboscopy (VS) uses an indirect physiological signal to predict
      the phase of the vocal fold vibratory cycle for sampling. Simulated stroboscopy
      (SS) extracts the phase of the glottal cycle directly from the changing glottal
      area in the high-speed videoendoscopy (HSV) image sequence. The purpose of this
      study is to determine the reliability of SS relative to VS for clinical
      assessment of vocal fold vibratory function in patients with mass lesions.
      Methods: VS and SS recordings were obtained from 28 patients with vocal fold mass
      lesions before and after phonomicrosurgery and 17 controls who were vocally
      healthy. Two clinicians rated clinically relevant vocal fold vibratory features
      using both imaging techniques, indicated their internal level of confidence in
      the accuracy of their ratings, and provided reasons for low or no confidence.
      Results: SS had fewer asynchronous image sequences than VS. Vibratory outcomes
      were able to be computed for more patients using SS. In addition, raters
      demonstrated better interrater reliability and reported equal or higher levels of
      confidence using SS than VS. Conclusion: Stroboscopic techniques on the basis of
      extracting the phase directly from the HSV image sequence are more reliable than
      acoustic-based VS. Findings suggest that SS derived from high-speed
      videoendoscopy is a promising improvement over current VS systems.

PMID- 27716855
TI  - Comments on Evaluation of Central and Peripheral Visual Field Concordance in
      Glaucoma.

PMID- 27716856
TI  - Author Response: Comments on Evaluation of Central and Peripheral Visual Field
      Concordance in Glaucoma.

PMID- 27716857
TI  - Thyroid Dysfunction and Ten-Year Incidence of Age-Related Macular Degeneration.
AB  - Purpose: Epidemiologic evidence of a relationship between thyroid dysfunction and
      age-related macular degeneration (AMD) is inconsistent and unclear. We aimed to
      assess the prospective associations between serum thyroid-stimulating hormone
      (TSH) and free thyroxine (FT4) measurements, as well as thyroid dysfunction
      (hyperthyroidism and hypothyroidism) and incidence of AMD. Methods: Categories of
      thyroid dysfunction were defined according to a serum TSH screen followed by
      serum FT4 assessment, and were available in 906 participants (aged 55+ years) at
      risk of AMD incidence (from 1997-1999 to 2007-2009). Continuous serum FT4
      measures were available regardless of TSH screening results in 583 participants
      at risk of AMD incidence. Age-related macular degeneration was assessed from
      retinal photographs. Results: Participants with overt hyperthyroidism compared to
      those with normal thyroid function at baseline had increased risk of developing
      any incident AMD, after adjusting for age, sex, smoking, fish consumption, and
      variants in AMD susceptibility genes (CFH and ARMS2): odds ratio (OR) 3.51 (95%
      confidence interval [CI] 1.16-10.65). Participants who reported current use of
      thyroxine (n = 67; 7.3%) versus those who were not current users (n = 839) had a
      68% increased risk of incident AMD, multivariable-adjusted OR 1.68 (95% CI 1.01
      2.82). Similarly, participants who had ever been on thyroxine medication (n = 77;
      8.4%) compared to those who had never been on thyroxine (n = 829) also had a
      higher risk of any AMD, multivariable-adjusted OR 1.91 (95% CI 1.18-3.09).
      Conclusions: Overt hyperthyroidism was independently associated with an increased
      risk of incident AMD. Thyroxine usage in older adults was also positively
      associated with incidence of AMD.

PMID- 27716859
TI  - Friendship: Operationalizing the Intangible to Improve Friendship-Based Outcomes
      for Individuals With Autism Spectrum Disorder.
AB  - Purpose: Individuals with autism spectrum disorder (ASD) have social deficits
      that affect making and maintaining friends. Many empirically tested methods to
      address these social deficits are available, yet difficulties related to the
      establishment and maintenance of authentic friendships persist. Method: This
      viewpoint article (a) briefly reviews the current state of the science relative
      to social and friendship skills training for individuals with ASD, (b) considers
      the potential links (or lack thereof) between current social and friendship skill
      interventions for individuals with ASD and outcomes related to making and
      maintaining friends, (c) examines how friendship-related outcomes might be
      maximized, and (d) proposes a framework for intervention planning that may
      promote these valued outcomes. Results: There are several key concepts to
      consider in planning intervention targeting friendship as an outcome. These
      concepts include (a) equal status, (b) mutually motivating and authentic
      opportunities for interaction, and (c) frequent opportunities for interaction.
      Conclusions: There are many aspects about friendship development that cannot be
      controlled or contrived. Much is still to be learned about the achievement of
      better friendships for individuals with ASD. Reconceptualizing the way we design
      intervention may promote better outcomes for individuals on the autism spectrum.

PMID- 27716858
TI  - Towards a Theory of Learning for Naming Rehabilitation: Retrieval Practice and
      Spacing Effects.
AB  - Purpose: The purpose of this article was to examine how different types of
      learning experiences affect naming impairment in aphasia. Methods: In 4 people
      with aphasia with naming impairment, we compared the benefits of naming treatment
      that emphasized retrieval practice (practice retrieving target names from long
      term memory) with errorless learning (repetition training, which preempts
      retrieval practice) according to different schedules of learning. The design was
      within subjects. Items were administered for multiple training trials for
      retrieval practice or repetition in a spaced schedule (an item's trials were
      separated by multiple unrelated trials) or massed schedule (1 trial intervened
      between an item's trials). In the spaced condition, we studied 3 magnitudes of
      spacing to evaluate the impact of effortful retrieval during training on the
      ultimate benefits conferred by retrieval practice naming treatment. The primary
      outcome was performance on a retention test of naming after 1 day, with a follow
      up test after 1 week. Results: Group analyses revealed that retrieval practice
      outperformed errorless learning, and spaced learning outperformed massed learning
      at retention test and at follow-up. Increases in spacing in the retrieval
      practice condition yielded more robust learning of retrieved information.
      Conclusion: This study delineates the importance of retrieval practice and
      spacing for treating naming impairment in aphasia.

PMID- 27716860
TI  - Safety and effectiveness of a long, partially covered metal stent for endoscopic
      ultrasound-guided hepaticogastrostomy in patients with malignant biliary
      obstruction.
AB  - Background and study aims: Endoscopic ultrasound (EUS)-guided biliary drainage
      (EUS-BD) is potentially complicated by bile leak and stent migration. The aim of
      this study was to evaluate the safety and effectiveness of a long (>= 10 cm),
      partially covered metal stent (LP-CMS) for EUS-guided hepaticogastrostomy (EUS
      HGS) for malignant biliary obstruction. Both the stent length and the uncovered
      portion at the proximal end of the LP-CMS are designed to prevent stent
      migration. Patients and methods: A total of 33 patients undergoing EUS-HGS using
      an LP-CMS in four centers were retrospectively studied. Technical and clinical
      success, adverse events, and recurrent biliary obstruction were evaluated.
      Results: Gastric outlet obstruction (76 %) and surgically altered anatomy (15 %)
      were two major reasons for EUS-HGS. The technical and clinical success rates were
      100 %. The median intragastric stent length was 54 mm. The adverse event rate was
      9 %. No stent migration was observed. Recurrent biliary obstruction developed in
      24 %, with a median cumulative time to recurrence of 8.5 months. Conclusions: EUS
      HGS using an LP-CMS for unresectable malignant biliary obstruction was safe and
      effective.

PMID- 27716861
TI  - Radiofrequency ablation for the management of occluded biliary metal stents.
AB  - Background and study aim: Obstruction of biliary self-expandable metal stents
      (SEMSs) is seen frequently. Radiofrequency ablation (RFA) causes tissue necrosis.
      This study aimed to assess the efficacy of RFA for management of occluded SEMS.
      Patients and methods: Patients with biliary malignancy and treated for an
      occluded SEMS were retrospectively reviewed. The study group comprised patients
      treated with RFA using an Habib endoprobe inside the SEMS. The control group
      comprised patients treated only with insertion of a plastic stent into an
      occluded SEMS. The end points were; 90-day stent patency rate, time to stent
      reocclusion, 30-day mortality, and 3 - and 6-month survival rates. Results:
      During the 5-year study period 25 patients with an occluded SEMS underwent RFA
      and 25 patients underwent a plastic stent placement only. Both groups were
      matched for age and diagnosis. Immediate biliary drainage was restored in all
      patients. In the RFA group, the stenosis was ablated successfully in 14 patients
      (56 %); ablation failed in 11 and a plastic stent was then inserted into the SEMS
      for these. The control group had only placement of a plastic stent across the
      stenosis. Stent patency rate at 90 days was 56 % and 24 % in the RFA and control
      groups, respectively (P = 0.04). The mean stent patency time was significantly
      longer in the RFA group compared to the control group (119.5 vs. 65.3 days, P =
      0.03). Conclusion: The application of RFA for occluded SEMS improves stent
      patency. RFA is an alternative treatment of tissue ingrowth in malignant biliary
      obstruction.

PMID- 27716862
TI  - Effect of Body Position on Energy Expenditure of Preterm Infants as Determined by
      Simultaneous Direct and Indirect Calorimetry.
AB  - Background Indirect calorimetry is the standard method for estimating energy
      expenditure in clinical research. Few studies have evaluated indirect calorimetry
      in infants by comparing it with simultaneous direct calorimetry. Our purpose was
      (1) to compare the energy expenditure of preterm infants determined by these two
      methods, direct calorimetry and indirect calorimetry; and (2) to examine the
      effect of body position, supine or prone, on energy expenditure. Study Design We
      measured energy expenditure by simultaneous direct (heat loss by gradient-layer
      calorimeter corrected for heat storage) and indirect calorimetry (whole-body
      oxygen consumption and carbon dioxide production) in 15 growing preterm infants
      during two consecutive interfeeding intervals, once in the supine position and
      once in the prone position. Results The mean energy expenditure for all
      measurements in both positions did not differ significantly by the method used:
      2.82 (standard deviation [SD] 0.42) kcal/kg/h by direct calorimetry and 2.78 (SD
      0.48) kcal/kg/h by indirect calorimetry. The energy expenditure was significantly
      lower, by 10%, in the prone than in the supine position, whether examined by
      direct calorimetry (2.67 vs. 2.97 kcal/kg/h, p < 0.001) or indirect calorimetry
      (2.64 vs. 2.92 kcal/kg/h, p = 0.017). Conclusion Direct calorimetry and indirect
      calorimetry gave similar estimates of energy expenditure. Energy expenditure was
      10% lower in the prone position than in the supine position.

PMID- 27716863
TI  - Severe Vitamin D Deficiency in Human Immunodeficiency Virus-Infected Pregnant
      Women is Associated with Preterm Birth.
AB  - Background Low maternal vitamin D has been associated with preterm birth (PTB).
      Human immunodeficiency virus (HIV)-infected pregnant women are at risk for PTB,
      but data on maternal vitamin D and PTB in this population are scarce. Methods In
      a cohort of Latin American HIV-infected pregnant women from the National
      Institute of Child Health and Human Development International Site Development
      Initiative protocol, we examined the association between maternal vitamin D
      status and PTB. Vitamin D status was defined as the following 25-hydroxyvitamin D
      levels: severe deficiency (< 10 ng/mL), deficiency (10-20 ng/mL), insufficiency
      (21-29 ng/mL), and sufficiency (>=30 ng/mL). PTB was defined as delivery at < 37
      weeks' gestational age (GA). Logistic regression was used to assess the
      association between maternal vitamin D status and PTB. Results Of 715 HIV
      infected pregnant women, 13 (1.8%) were severely vitamin D deficient, 224 (31.3%)
      were deficient, and 233 were (32.6%) insufficient. Overall, 23.2% (166/715) of
      pregnancies resulted in PTB (median GA of PTBs = 36 weeks [interquartile range:
      34-36]). In multivariate analysis, severe vitamin D deficiency was associated
      with PTB (odds ratio = 4.7, 95% confidence interval: 1.3-16.8]). Conclusion
      Severe maternal vitamin D deficiency is associated with PTB in HIV-infected Latin
      American pregnant women. Further studies are warranted to determine if vitamin D
      supplementation in HIV-infected women may impact PTB.

PMID- 27716864
TI  - Exogenous Carbohydrate Reduces Cortisol Response from Combined Mental and
      Physical Stress.
AB  - Combined mental and physical stress is associated with exacerbated cortisol
      production which may increase risk for the progression of cardiovascular disease
      in individuals working in high-stress occupations (e.g., firefighters, military
      personnel, etc.). Carbohydrate (CHO) ingestion prior to physical stress may
      attenuate cortisol concentrations. This project was the first to investigate the
      effect of CHO ingestion on cortisol response from combined mental and physical
      stress. 16 men 21-30 years old were randomly assigned a 6.6% CHO beverage or non
      CHO control 15 min prior to performing a dual-concurrent-stress challenge. This
      consisted of physical stress (i.e., steady state exercise) combined with
      computerized mental challenges. Blood was sampled 70, 40, and 15 min before
      exercise, immediately at onset of exercise, 10, 20, 30, 35 min during exercise,
      and 15, 30, 45, and 60 min after exercise. There was a significant main effect
      for treatment regarding mean cortisol concentrations (F=5.30, P=0.0219). The
      total area under curve for cortisol was less when CHO was ingested (T7=4.07,
      P=0.0048). These findings suggest that CHO ingestion immediately prior to
      combined mental and physical stress may attenuate cortisol responses.

PMID- 27716865
TI  - Breaking up Prolonged Sitting does not Alter Postprandial Glycemia in Young,
      Normal-Weight Men and Women.
AB  - A randomized, controlled, cross-over study was used to investigate the effects of
      breaking up prolonged sitting with low intensity physical activity on
      postprandial blood glucose concentrations in healthy, young, normal-weight
      adults. 14 men (n=6) and women (n=8) were assigned to 2.5 h of prolonged sitting
      (CON) and 2.5 h of prolonged sitting with 2-min bouts of walking every 20 min
      (LIPA). After ingesting a standardized test drink, capillary blood was sampled
      every 10 min to establish a postprandial blood glucose profile. Based on
      individual glucose responses, peak blood glucose, time-to-peak glucose, and
      incremental area under the glucose curve (iAUC) were determined. Paired sample t
      tests were used to detect differences between trials. Peak blood glucose (p=0.55)
      and iAUC (CON: 252 mmol.L-1.2.5 h-1 [163-340]; LIPA: 214 mmol.L-1.2.5 h-1 [146
      282]; p=0.45) were not different between trials. Also, time-to-peak glucose was
      not different between LIPA and CON (p=0.37). Taking advantage of high temporal
      resolution blood glucose profiles, we showed that breaking up prolonged sitting
      with low-intensity physical activity does not alter the postprandial blood
      glucose response in young, healthy, normal-weight adults. Our results indicate
      that postprandial glycemic control is maintained during prolonged sitting in
      young, healthy adults.

PMID- 27716866
TI  - [Is DRG Coding too Important to be Left to Physicians? - Evaluation of Economic
      Efficiency by Health Economists in a University Medical Centre].
AB  - Background: We investigated and evaluated the cost effectiveness of coding by
      health care economists in a centre for orthopaedics and trauma surgery in
      Germany, by quantifying and comparing the financial efficiency of physicians with
      basic knowledge of the DRG-system with the results of healthcare economists with
      in-depth knowledge (M.Sc.). In addition, a hospital survey was performed to
      establish how DRG-coding is being performed and the identity of the persons
      involved. Material and Methods: In a prospective and controlled study, 200 in
      patients were coded by a healthcare economist (study group). Prior to that, the
      same cases were coded by physicians with basic training in the DRG-system, who
      made up the control group. All cases were picked randomly and blinded without
      informing the physicians coding the controls, in order to avoid any Hawthorne
      effect. We evaluated and measured the effective weighting within the G-DRG, the
      DRG returns per patient, the overall DRG return, and the additional time needed.
      For the survey, questionnaires were sent to 1200 German hospitals. The completed
      questionnaire was analysed using a statistical program. Results: The return
      difference per patient between controls and the study group was significantly
      greater (2472 +/- 337 ?; p < 0.05); the overall return was raised by 494,500 ?.
      The mean additional time needed was 11.32 +/- 0.8 min per case, resulting in an
      increase in proceeds of 218 +/- 38 ? per minute. 2.5 % of all cases had to be
      devaluated by the health economist after the initial coding by the control group.
      Returned sheets of 60 hospitals were evaluated. The median level of DRG case
      reports was 1277 (2500-62,300). Coding was performed in 69 % of cases by doctors,
      19 % by skilled specialists for DRG coding and in 8 % together. Overall
      satisfaction with the DRG was described by 61 % of respondents as good or
      excellent. Conclusion: Our prospective and controlled study quantifies the cost
      efficiency of health economists in a centre of orthopaedics and trauma surgery in
      Germany for the first time. We provide some initial evidence that health
      economists can enhance the CMI, the resulting DRG return per patient as well as
      the overall DRG return. Data from the survey shows that in many hospitals there
      is great reluctance to leave the coding to specialists only.

PMID- 27716867
TI  - [Are Higher Prices for Larger Femoral Heads in Total Hip Arthroplasty Justified
      from the Perspective of Health Care Economics? An Analysis of Costs and Effects
      in Germany].
AB  - Background: In total hip arthroplasty (THA), femoral head diameter has not been
      regarded as a key parameter which should be restored when reconstructing joint
      biomechanics and geometry. Apart from the controversial discussion on the
      advantages and disadvantages of using larger diameter heads, their higher cost is
      another important reason that they have only been used to a limited extent. The
      goal of this study was to analyse the price structure of prosthetic heads in
      comparison to other components used in THA. A large group of patients with hip
      endoprostheses were evaluated with respect to the implanted socket diameter and
      thus the theoretically attainable head diameter. Materials and Methods: The
      relative prices of various THA components (cups, inserts, stems and ball heads)
      distributed by two leading German manufacturers were determined and analysed.
      Special attention was paid to different sizes and varieties in a series of
      components. A large patient population treated with THA was evaluated with
      respect to the implanted cup diameter and therefore the theoretically attainable
      head diameter. Results: The pricing analysis of the THA components of two
      manufacturers showed identical prices for cups, inserts and stems in a series. In
      contrast to this, the prices for prosthetic heads with a diameter of 36-44 mm
      were 11-50 % higher than for 28 mm heads. Identical prices for larger heads were
      the exception. The distribution of the head diameter in 2719 THA cases showed
      significant differences between the actually implanted and the theoretically
      attainable heads. Conclusion: There are proven advantages in using larger
      diameter ball heads in THA and the remaining problems can be solved. It is
      therefore desirable to correct the current pricing practice of charging higher
      prices for larger components. Instead, identical prices should be charged for all
      head diameters in a series, as is currently established practice for all other
      THA components. Thus when reconstructing biomechanics and joint geometry in THA,
      it should be possible to recover not only leg length, femoral offset and
      antetorsion of the femoral neck, but also to approximately restore the diameter
      of the femoral head and thereby optimise the functional outcome.

PMID- 27716868
TI  - Twelve-month quality of life improvement and all-cause mortality in elderly
      patients undergoing transcatheter aortic valve replacement.
AB  - PURPOSE: Restoration of quality of life (QoL) and improvement of clinical
      outcomes is crucial in elderly patients undergoing transcatheter aortic valve
      implantation (TAVI). We sought to evaluate changes in QoL and all-cause mortality
      12 months after TAVI. METHODS: A total of 101 patients who underwent TAVI were
      included. Patients were followed for 12 months. QoL was assessed at baseline and
      at 1, 6 and 12 months after TAVI using EQ-5D-3L with a visual analog scale (VAS).
      RESULTS: Patients who reported some problems with mobility at baseline showed
      better mobility after 12 months (p = 0.001). On the other hand, those who
      reported issues with self-care, usual activity or pain did not show significant
      improvement (p = 0.41; p = 0.12; p = 0.27, respectively). Patients reporting
      anxiety at baseline improved 12 months later (p = 0.003). VAS score showed an
      incremental increase during follow-up (p<0.001). Transfemoral access was
      associated with higher VAS score values after 1 month (median (IQR): 65.0 (50.0
      75.0) vs. 54.0 (50.0-60.0); p = 0.019) but not after 12 months (70.0 (62.5-80.0)
      vs. 67.5 (55.0-70.0); p = 0.07) as compared to non-transfemoral access. In
      multivariable regression analysis, only age and the presence of coronary chronic
      total occlusion were independently associated with VAS score at 12 months. In
      hospital, 1-, 6- and 12-month mortality rates were 6.9%, 10.9%, 15.8 and 17.8%,
      respectively. CONCLUSIONS: TAVI provides improved QoL with relatively good
      clinical outcomes. However, not all components of QoL may be improved. Patients
      treated with transfemoral access might have better QoL than those who had non
      transfemoral access, especially early after TAVI.

PMID- 27716869
TI  - Biopolyester-based systems containing naturally occurring compounds with enhanced
      thermo-oxidative stability.
AB  - BACKGROUND: This work presents a sustainable approach for the stabilization of
      polylactic acid (PLA) against thermo-oxidative aging. METHODS: Naturally
      occurring phenolic and polyphenolic compounds, such as ferulic acid (FerAc),
      vanillic acid (VanAc), quercetin (Querc) and vitamin E (VitE), were introduced
      into PLA. RESULTS: The preliminary characterization of the systems formulated
      containing different amounts of natural stabilizers showed that all compounds
      used acted as plasticizers, leading to a decrease in rheological functions with
      respect to neat PLA, without significantly modifying the crystallinity of the raw
      material. The study of the thermo-oxidative behavior of neat PLA and PLA/natural
      compound systems, performed by spectrometric and thermal analyses, indicated that
      all stabilizers considered were able to exert a remarkable antioxidant action
      against thermo-oxidative phenomena. CONCLUSIONS: All natural compounds considered
      are thus proposed as ecofriendly stabilizers, to get fully bio-based polymer
      systems with enhanced thermo-oxidative stability, suitable for biomedical
      applications.

PMID- 27716870
TI  - Effect of cold drawing on mechanical properties of biodegradable fibers.
AB  - PURPOSE: Biodegradable polymers are currently gaining importance in several
      fields, because they allow mitigation of the impact on the environment related to
      disposal of traditional, nonbiodegradable polymers, as well as reducing the
      utilization of oil-based sources (when they also come from renewable resources).
      Fibers made of biodegradable polymers are of particular interest, though, it is
      not easy to obtain polymer fibers with suitable mechanical properties and to
      tailor these to the specific application. The main ways to tailor the mechanical
      properties of a given biodegradable polymer fiber are based on crystallinity and
      orientation control. However, crystallinity can only marginally be modified
      during processing, while orientation can be controlled, either during hot drawing
      or cold stretching. In this paper, a systematic investigation of the influence of
      cold stretching on the mechanical and thermomechanical properties of fibers
      prepared from different biodegradable polymer systems was carried out. METHODS:
      Rheological and thermal characterization helped in interpreting the orientation
      mechanisms, also on the basis of the molecular structure of the polymer systems.
      RESULTS AND CONCLUSIONS: It was found that cold drawing strongly improved the
      elastic modulus, tensile strength and thermomechanical resistance of the fibers,
      in comparison with hot-spun fibers. The elastic modulus showed higher increment
      rates in the biodegradable systems upon increasing the draw ratio.

PMID- 27716871
TI  - Controlled release of strontium through neutralization reaction within a
      methoxy(polyethylene glycol)-polyester hydrogel.
AB  - BACKGROUND: The aim of this study was to develop a minimally invasive hydrogel
      system that can release strontium ions, an element that has been shown to
      increase osteoblast proliferation and prohibit bone resorption, in a controlled
      manner. METHODS: SrCO3 was selected as the salt of choice due to potential acid
      neutralization reaction between SrCO3 and degradation by-products of
      methoxy(polyethylene glycol)-co-poly(lactic-co-glycolic acid) (mPEG-PLGA):
      namely, lactic acid and glycolic acid. SrCO3 was incorporated into mPEG-PLGA
      hydrogel, and the system was assessed for gelation properties, drug release and
      biocompatibility. RESULTS: SrCO3 incorporation at hydrogel to SrCO3 ratios of
      5:1, 3:1 and 1:1 (wt%) did not compromise the thermosensitivity of mPEG-PLGA
      hydrogels. Furthermore, incorporation of SrCO3 at 1:1 ratio prevented copolymer
      self-catalysis and decreased hydrogel weight loss from 85% to 61% in vitro after
      30 days. During the 30-day time frame, zero-order strontium release was observed
      and was correlated to hydrogel degradation and acidity. The addition of SrCO3
      also improved in vivo hydrogel biocompatibility, due to moderation of acidic
      microenvironment and amelioration of inflammatory response. CONCLUSIONS: These
      results showed that the described system is suitable for the extended release of
      strontium and exhibits potential for localized treatment for osteoporosis or as a
      bone void filler.

PMID- 27716873
TI  - The current status of PARP inhibitors in ovarian cancer.
AB  - Recent advances in our understanding of the molecular biology of epithelial
      ovarian cancer have led to the development of a number of targeted therapies,
      including poly-ADP-ribose polymerase (PARP) inhibitors. PARP inhibitors are a
      novel class of therapeutic agents that target tumors with deficiencies in the
      homologous recombination DNA repair pathway. Early studies have shown significant
      efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations. It has
      become evident that BRCA wild-type patients with other defects in the homologous
      recombination repair pathway benefit from this therapeutic approach. Importantly,
      companion homologous recombination deficiency scores are being developed to help
      guide the selection of patients most likely to gain clinical benefit from PARP
      inhibition. Olaparib, the first and most extensively investigated PARP inhibitor,
      is now licensed in Europe for maintenance treatment of patients with platinum
      sensitive relapsed BRCA-mutated (germline or somatic) high-grade serous ovarian
      cancer who have responded to platinum-based chemotherapy. In the United States,
      olaparib is licensed for treatment of patients with germline BRCA-mutated ovarian
      cancer who have received 3 or more lines of chemotherapy. There are a number of
      other PARP inhibitors in late phase clinical development in ovarian cancer
      including rucaparib, niraparib, veliparib, and talazoparib. This review will
      focus on the current evidence for PARP inhibitors in ovarian cancer and discuss
      ongoing clinical trials and future research directions in this rapidly evolving
      area.

PMID- 27716872
TI  - Bioencapsulation technologies in tissue engineering.
AB  - Bioencapsulation technologies have played an important role in the developing
      successes of tissue engineering. Besides offering immunoisolation, they also show
      promise for cell/tissue banking and the directed differentiation of stem cells,
      by providing a unique microenvironment. This review describes bioencapsulation
      technologies and summarizes their recent progress in research into tissue
      engineering. The review concludes with a brief outlook regarding future research
      directions in this field.

PMID- 27716875
TI  - Advantage of deep inspiration breath hold in left-sided breast cancer patients
      treated with 3D conformal radiotherapy.
AB  - PURPOSE: To compare 3D-conformal radiotherapy (3D-CRT) treatment plans based on
      free-breathing (FB) and deep inspiration breath hold (DIBH) and investigated
      whether DIBH technique enables a decrease of cardiac left anterior descending
      coronary artery (LADCA) and lungs dose with respect to the FB. METHODS: Twenty
      three left-sided breast cancer patients referred for breast radiotherapy were
      included. The planning target volume (PTV) encompassed the breast and organs at
      risk including heart, LADCA, lungs, and contralateral breast, which were
      contoured in FB and DIBH CT scans. Dose to PTV was 50 Gy in 25 fractions. Two
      treatment plans were generated for each patient: FB-3D-CRT and DIBH-3D-CRT.
      Dosimetry parameters were obtained from dose volume histograms. Data were
      compared using the paired-sample Wilcoxon signed rank test. RESULTS: For heart,
      LADCA, and left lung, a significant dose reduction was found using DIBH
      technique. By using DIBH, an average reduction of 25% was observed in LADCA for
      the volume receiving 20 Gy and of 48% considering the mean heart dose.
      CONCLUSIONS: The DIBH technique results in a significant decrease of dose to the
      heart, LADCA, and left lung compared to FB.

PMID- 27716874
TI  - Temozolomide low-dose chemotherapy in newly diagnosed low-grade gliomas:
      activity, safety, and long-term follow-up.
AB  - PURPOSE: To explore the efficacy and toxicity of an extended schedule of
      temozolomide (50 mg/mq 1 week on/1 week off) in a population of newly diagnosed
      low-grade gliomas (LGG). METHODS: Primary endpoints were progression-free
      survival (PFS) at 12 and 24 months and response rate evaluated with Response
      Assessment in Neuro-Oncology Criteria. Secondary endpoints were clinical benefit
      (reduction of seizures frequency), reduction of steroid, and modifications of
      Karnofsky Performance Status. RESULTS: From 2006 to 2009, we enrolled 14
      consecutive patients with newly diagnosed LGG: 8 grade II astrocytomas, 2
      oligodendroglioma, and 4 oligo-astrocytoma. Temozolomide was administered for 18
      cycles (mean) per patient (range 3-24 cycles). In 57.5% (n = 8), we observed
      stable disease, 28.5% (n = 4) presented a minor response, and 14% (n = 2) showed
      progression. Five patients presented early progression during the first year of
      treatment and the study was stopped. A relevant clinical benefit was observed in
      85% of patients (seizure control). After 6 years of follow-up, only 4 patients
      died. Prolonged PFS was associated with 1p-19q codeletion over 1p-19q intact (35
      vs 4 months; p<0.04) and IDH1 mutation over IDH1 wild-type (36 vs 6 months;
      p<0.009). CONCLUSIONS: The study was interrupted for the high rate of progression
      observed in the first 14 patients enrolled. However, our results show that an
      extended low dose of temozolomide presents interesting activity with objective
      response and clinical benefit, but does not seem to prevent progression in
      patients presenting unfavorable molecular prognostic factors.

PMID- 27716876
TI  - Vestibular schwannomas treated with Cyberknife(r): clinical outcomes.
AB  - PURPOSE: Fractionated stereotactic radiotherapy (FSR) is a recognized treatment
      for vestibular schwannomas (VS). This study's aim is to present clinical outcomes
      and local control (LC) results for patients with VS treated with FSR using the
      Cyberknife(r) (CK) in 2 French cancer centers. METHODS: Patients treated with FSR
      for VS between 2007 and 2012 were retrospectively analyzed. Local control was
      determined using follow-up MRI. The hearing preservation (HP) rate was determined
      by analyzing pretreatment and posttreatment audiograms. RESULTS: Forty patients
      were treated for VS with the CK in both centers. The mean maximal VS dimension
      was 18.3 mm (range 3-30). The median follow-up was 36 months and the LC was 97%
      at 3 years of follow-up and 89% after 5 years. The HP rate was 83% and no facial
      nerve impairment was reported. CONCLUSIONS: Our results in terms of LC and HP
      rate are congruent with similar studies that use the CK to treat VS. It appears
      that the CK is safe and efficient in VS management even for large lesions.
      Further studies with larger cohorts are warranted.

PMID- 27716877
TI  - Simultaneous integrated bilateral breast and nodal irradiation with volumetric
      arc therapy: case report and literature review.
AB  - AIM: For simultaneous bilateral breast cancer (SBBC) treatment, conventional
      radiotherapy (RT) has a number of critical shortcomings. Thus, the usefulness of
      volumetric arc therapy (VMAT) for SBBC is undeniable. CASE REPORT: A 34-year-old
      woman with SBBC received neoadjuvant chemotherapy followed by breast-conserving
      surgery and bilateral lymph node dissection. Given the conservative surgery and
      the nodal involvement after neoadjuvant chemotherapy, bilateral adjuvant RT to
      the breasts and regional nodes with doses of 50 Gy in 25 fractions and a
      simultaneous integrated boost (SIB) of 60 Gy to the surgical bed was proposed.
      Monoisocentric VMAT using 2 pairs of arcs was performed with adequate target dose
      coverage and low doses to the organs at risk. The results of this case were
      compared with those of previous studies in terms of RT technique and irradiated
      volumes. CONCLUSIONS: VMAT is feasible and safe in the treatment of SBBC with SIB
      and nodal irradiation.

PMID- 27716878
TI  - Data quality in rare cancers registration: the report of the RARECARE data
      quality study.
AB  - PURPOSE: Rare cancers represent 22% of all tumors in Europe; however, the quality
      of the data of rare cancers may not be as good as the quality of data for common
      cancer. The project surveillance of rare cancers in Europe (RARECARE) had, among
      others, the objective of assessing rare cancer data quality in population-based
      cancer registries (CRs). Eight rare cancers were considered: mesothelioma, liver
      angiosarcoma, sarcomas, tumors of oral cavity, CNS tumors, germ cell tumors,
      leukemia, and malignant digestive endocrine tumors. METHODS: We selected data on
      18,000 diagnoses and revised, on the basis of the pathologic and clinical reports
      (but not on pathologic specimens), unspecified morphology and topography codes
      originally attributed by CR officers and checked the quality of follow-up of long
      term survivors of poor prognosis cancers. RESULTS: A total of 38 CRs contributed
      from 13 European countries. The majority of unspecified morphology and topography
      cases were confirmed as unspecified. The few unspecified cases that, after the
      review, changed to a more specific diagnosis increased the incidence of the
      common cancer histotypes. For example, 11% of the oral cavity epithelial cancers
      were reclassified from unspecified to more specific diagnoses: 8% were
      reclassified as squamous cell carcinoma (commoner) and only 1% as adenocarcinoma
      (rarer). The revision confirmed the majority of long-term survivors revealing a
      relative high proportion of mesothelioma long-term survivors. The majority of
      appendix carcinoids changed behavior from malignant to borderline lesions.
      CONCLUSIONS: Our study suggests that the problem of poorly specified morphology
      and topography cases is mainly one of difficulty in reaching a precise diagnosis.
      The awareness of the importance of data quality for rare cancers should increase
      among registrars, pathologists, and clinicians.

PMID- 27716879
TI  - 3D vision improves outcomes in early cervical cancer treated with laparoscopic
      type B radical hysterectomy and pelvic lymphadenectomy.
AB  - PURPOSE: To evaluate the alterations on surgical outcomes after of the
      implementation of 3D laparoscopic technology for the surgical treatment of early
      stage cervical carcinoma. METHODS: Data of patients undergoing type B radical
      hysterectomy (with or without bilateral salpingo-oophorectomy) and pelvic
      lymphadenectomy via 3D laparoscopy were compared with a historical cohort of
      patients undergoing type B radical hysterectomy via conventional laparoscopy.
      Complications (within 60 days) were graded per the Accordion severity system.
      RESULTS: Data of 75 patients were studied: 15 (20%) and 60 (80%) patients
      undergoing surgery via 3D laparoscopy and conventional laparoscopy, respectively.
      Baseline patient characteristics as well as pathologic findings were similar
      between groups (p>0.1). Patients undergoing 3D laparoscopy experienced a trend
      toward shorter operative time than patients undergoing conventional laparoscopy
      (176.7 +/- 74.6 vs 215.9 +/- 61.6 minutes; p = 0.09). Similarly, patients
      undergoing 3D laparoscopic radical hysterectomy experienced shorter length of
      hospital stay (2 days, range 2-6, vs 4 days, range 3-11; p<0.001) in comparison
      to patients in the control group, while no difference in estimated blood loss was
      observed (p = 0.88). No between-group difference in complication rate was
      observed. CONCLUSIONS: 3D technology is a safe and effective way to perform type
      B radical hysterectomy and pelvic node dissection in early-stage cervical cancer.
      Further large prospective studies are warranted in order to assess the cost
      effectiveness of the introduction of 3D technology in comparison to robotic
      assisted surgery.

PMID- 27716880
TI  - Peritoneal metastases from adrenal cortical carcinoma treated by cytoreductive
      surgery and hyperthermic intraperitoneal chemotherapy.
AB  - PURPOSE: Adrenal cortical carcinoma is a rare cancer that often presents in an
      advanced stage. Not only systemic metastases but also local recurrence and
      peritoneal metastases prevent long-term survival in these patients. METHODS: A
      profoundly symptomatic patient with extensive peritoneal metastases and local
      recurrence was treated using cytoreductive surgery (CRS) and hyperthermic
      intraperitoneal chemotherapy (HIPEC) with melphalan as the chemotherapy agent.
      RESULTS: Relative sparing of the small bowel within the abdomen and pelvis
      allowed a visible complete resection of all cancer. The HIPEC with melphalan was
      used to control microscopic residual disease. Similar surgical technology used in
      this patient could be used to prevent local recurrence and peritoneal metastases
      in patients at the time of resection of the primary adrenal cortical carcinoma.
      CONCLUSIONS: Rare diseases may have peritoneal metastases as a component of
      disease progression and profit from treatment with CRS plus HIPEC. The clinical
      features suggesting a favorable outcome from this combined treatment are relative
      sparing of small bowel and its mesentery, absence of disease outside the abdomen,
      low-grade disease, or limited extent of high-grade disease.

PMID- 27716881
TI  - "What if...": decisional regret in patients who discontinued active surveillance.
AB  - PURPOSE: To investigate the presence of regret in patients about having followed
      an active surveillance (AS) protocol. The secondary aim was to identify variables
      that influence regret. METHODS: From February 2006 to May 2014, 204 patients
      discontinued the AS protocols and were invited to enter the study.
      Sociodemographic variables were collected at AS enrollment, together with health
      related quality of life (Functional Assessment of Cancer Therapy-Prostate version
      [FACT-P]) and coping (Mini-Mental Adjustment to Cancer). Patients were asked to
      complete a Treatment Regret Scale as well as the FACT-P questionnaire. Clinical
      data were gathered, as well as time of stay within the AS protocol, reason for
      discontinuing AS, kind of post-AS treatment, and time elapsed since AS
      discontinuation. Questionnaires were completed by 105 patients (51.5% of those
      who had been invited to enter the study). RESULTS: Most of the patients had a low
      or null degree of regret on the Treatment Regret Scale from 0 to 100 (82/105
      patients [78.1%] obtained a score <30, and about 30% of the sample had a score
      equal to zero). Only 5 patients (4.7%) scored 60 or more, indicating some degree
      of regret. None of the statistical tests between regret scores and a number of
      analyzed variables reached significance. CONCLUSIONS: These results show that the
      degree of regret about following an AS protocol and after its discontinuation
      because of entering active treatment was very low. The regret after AS was not
      related to sociodemographic or clinical factors.

PMID- 27716882
TI  - Bilateral lymph node micrometastases and seminal vesicle invasion associated with
      same clinical predictors in localized prostate cancer.
AB  - AIM: To determine clinical factors associated with multiple bilateral lymph node
      micrometastases and seminal vesicle invasion (pT3b) in organ-confined prostate
      cancer (PCa). METHODS: The study excluded patients under androgen deprivation,
      with lymph node involvement (cN1 status), and having undergone unilateral pelvic
      lymph node dissection (PLND) during radical prostatectomy (RP). Lymph node
      micrometastases were classified as unilateral (pN1m) and bilateral (pN1b).
      Analysis considered multivariate multinomial logistic regression models. RESULTS:
      Between January 2013 and March 2015, 140 patients underwent PLND during RP. Lymph
      node micrometastases were detected in 28 cases (20%) including pN1m in 19 (13.6%)
      and pN1b in 9 (6.4%). Independent clinical predictors of pN1b included prostate
      specific antigen (PSA, ug/L) >12.5 (odds ratio [OR] = 43.0), proportion of
      positive biopsy cores (PBC) >0.57 (OR = 6.7), and biopsy Gleason grade (bGG) >3
      (OR = 7.5). Independent pT3b predictors included PSA>12.5 (OR = 3.8), PBC>0.57
      (OR = 4.1), and bGG>3 (OR = 3.8). CONCLUSIONS: In cN0 patients with localized PCa
      undergoing PLND, a nonnegligible rate of multiple lymph node micrometastases was
      detected (32.2%). In the natural history of PCa, there is a close association
      between pT3b and pN1b disease. Prostate cancer patients who are at high risk of
      extraglandular extension need selective pelvic staging by multiparametric
      magnetic resonance imaging to assess seminal vesicle invasion. Operated patients
      with pT3b and pNx status need close PSA monitoring because of the high
      probability of occult multiple bilateral lymph node micrometastases.

PMID- 27716883
TI  - LODDS is superior to lymph node ratio for the prognosis of node-positive rectal
      cancer patients treated with preoperative radiotherapy.
AB  - PURPOSE: Yielding pathologic-lymph node ratio (yp-LNR) was considered to be a
      better staging system than yp-N stage in rectal cancer patients treated with
      preoperative radiotherapy (pre-RT). We aimed to compare the predictive ability of
      yielding pathologic log odds of positive lymph nodes (yp-LODDS) with that of yp
      LNR for cancer-specific survival (CSS) in stage III rectal cancer patients
      treated with pre-RT. METHODS: We analyzed stage III rectal cancer patients
      treated with pre-RT in the Surveillance, Epidemiology and End Results (SEER)
      database. Patients were classified into 4 groups, yp-LNR1 to 4, based on the LNR
      cutoff points 0.25, 0.50, and 0.75. Subjects were categorized into 5 groups, yp
      LODDS1 to yp-LODDS5, based on the LODDS cutoff points -1, 0, 1, and 2. Univariate
      and multivariate Cox proportional hazards models were performed to analyze the
      risk factors for survival outcome. RESULTS: A total of 4,612 patients were
      included from the SEER database. Patients in the yp-LNR4 group could be further
      divided into yp-LODDS4 and yp-LODDS5 groups with 5-year CSS of 47.6% and 31.5%,
      respectively (p<0.001). In the multivariate analysis without yp-LODDS, yp-LNR was
      an independent prognostic factor (hazard ratio [HR] 2.006, 95% confidence
      interval [CI] 1.619-2.484, p<0.001). However, after adjusting for yp-LODDS, yp
      LNR was no longer associated with CSS (p = 0.393), and yp-LODDS was identified as
      an independent prognostic factor (HR 1.274, 95% CI 1.069-1.520, p = 0.007).
      CONCLUSIONS: The prognostic value of yp-LNR can be confounded by yp-LODDS. In
      stage III rectal cancer patients treated with pre-RT, yp-LODDS has superior
      discrimination power over yp-LNR and can more accurately evaluate CSS.

PMID- 27716884
TI  - Conservative approach for a solitary fibrous tumor of the kidney.
AB  - INTRODUCTION: Solitary fibrous tumor (SFT) of the kidney represents a rare
      neoplasm, and its malignant potential seems to be scarce. Classically, a radical
      nephrectomy is regarded as the treatment of choice for this condition. CASE
      REPORT: We present the case of a 37-year-old male patient who underwent left
      robotic clampless partial nephrectomy of an SFT of the kidney. Our patient has
      been followed-up carefully, and at 15-month examination, he is free of
      recurrence. This is the second case of an SFT managed through a conservative
      approach. CONCLUSIONS: In our opinion, according to tumor's dimensions, partial
      nephrectomy may be considered for treating small SFTs.

PMID- 27716885
TI  - Mitomycin C from birth to adulthood.
AB  - Mitomycin C (MMC) intravesical therapy for "superficial" papillary bladder tumors
      was firstly introduced in the early seventies with promising results. In the
      following years, several pharmacokinetic studies investigated its mechanism of
      action to optimize the intravesical administration. Numerous studies confirmed
      thereafter both the ablative and the prophylactic efficacy and the low toxicity
      of MMC when intravesically given. In 1984, a complete response rate of 42% in 60
      patients not responsive to thiotepa was reported with intravesical MMC at the
      dose of 40 mg diluted in 40 ml for 8 weeks. In the following decades, many large
      randomized studies showed the benefit of intravesical prophylaxis with MMC versus
      transurethral resection (TUR) alone. Since 2002, the role of adjuvant
      intravesical chemotherapy and of an early MMC instillation in preventing
      recurrence compared with TUR alone has been confirmed by large meta-analyses and
      stated by the European Association of Urology (EAU) guidelines. The need for
      further intravesical chemotherapy after the early instillation in patients at
      intermediate-high risk of recurrence has been proved by several trials. Although
      intravesical Bacillus Calmette-Guerin (BCG) is considered the best choice for
      high-risk patients and MMC for the low-risk group, both MMC and BCG can be given
      to prevent recurrence in intermediate-risk patients. However, the higher efficacy
      of BCG over MMC is evident only if maintenance regimen is administered. Despite
      its proven efficacy, immediate intravesical MMC is not yet fully entered in
      common clinical practice and efforts should be made by the urologists to optimize
      its adoption.

PMID- 27716886
TI  - The impact of core length on prostate cancer diagnosis during a standard 14-core
      prostate biopsy scheme.
AB  - INTRODUCTION: Even if many studies in the literature purposed to evaluate the
      improvement of the prostate biopsy (PBx), few studies assessed the diagnostic
      value of core length in PBx. In this study, we evaluated the length of needle
      cores sampled during transrectal PBx (TRUSBx) and its impact on cancer diagnosis
      in a standard 14-core scheme. METHODS: Medical records of 573 patients who
      underwent an initial TRUSBx with 14-cores scheme for suspicious prostate cancer
      (PCa) at our Department were reviewed. The PBx procedure and pathological
      evaluation were standardized. Cores lengths were compared in patients with versus
      without cancer, and were divided into group A and B, respectively. Statistical
      analysis was done to define an acceptable cut-off for biopsy length. RESULTS: The
      mean age of the entire cohort was 62.1 +/- 7.2 years, while median total prostate
      specific antigen (PSA) and prostate volume were 4.2 ng/ml and 44.7 ml,
      respectively. PCa was showed in 33.3% of patients. Mean core length in group A
      versus B was 11.9 +/- 3.9 versus 11.1 +/- 3.2 mm (p = 0.016). Thus, core lengths
      were significantly longer in patients with cancer. There were no statistically
      significant differences when we considered the whole length of cores sampled from
      the right lobe (p = 0.58) and left lobe (p = 0.34). CONCLUSIONS: The cancer
      detection rates in cores may be increased by core length in PCa patients during a
      TRUSBx. Our results suggest a core length of greater than 11.8 mm as a cut-off
      for quality warranty.

PMID- 27716887
TI  - Intravesical electro-osmotic administration of mitomycin C.
AB  - Bladder cancer is very common and most cases are diagnosed as nonmuscle invasive
      disease, which is characterized by its propensity to recur and progress.
      Intravesical therapy is used to delay recurrence and progression, while
      cystectomy is reserved for patients who are refractory to transurethral resection
      and intravesical therapy. There is an increasing interest in methods to enhance
      the delivery of intravesical chemotherapeutic agents to improve efficacy. In
      vitro and in vivo studies demonstrated that electro-osmosis of mitomycin C (MMC)
      is more effective in delivering this drug into the urothelium, lamina propria,
      and superficial muscle layers of the bladder wall than is passive transport.
      Higher MMC tissue concentrations might have a clinical impact in the treatment of
      nonmuscle invasive bladder cancer (NMIBC). In randomized trials, intravesical
      electro-osmotic MMC was associated with superior response rate in high-risk NMIBC
      cancer, compared with passive diffusion MMC transport. New strategies such as
      intravesical Bacillus Calmette-Guerin (BCG) combined with electro-osmotic MMC as
      well as intravesical pre-operative electro-osmotic MMC provided promising results
      in terms of higher remission rates and longer remission times.Device-assisted
      intravesical chemotherapy may be a useful ancillary procedure in the treatment of
      NMIBC. Its evaluation must be planned with respect to the technical functioning
      of equipment and their use for a clear purpose to avoid the financial and human
      costs associated with incorrect therapies.

PMID- 27716888
TI  - Efficacy and safety of percutaneous nephrolithotomy with adult standard size
      instruments in children under 3 years of age: a 10 years single-center
      experience.
AB  - BACKGROUND: Using percutaneous nephrolitotomy (PCNL) with large adult instruments
      in treatment of pediatricurolithiasis is still in debate. This study was
      conducted to evaluate the efficacy and safety of PCNL with adult's instrument in
      treatment of patients less than 3 years old. METHODS: Data on patient
      characteristics and outcomes for 261 consecutive children undergoing PCNL at a
      Labbafinejad University Hospital were collected prospectively from September 2006
      to February 2016. Thirty-two children, with 34 renal units, who were treated with
      PCNL were enrolled in the study. All PCNL procedures were performed via subcostal
      approach with one access tract in all of them. Postoperative complications were
      evaluated according to the modified Clavien grading system. RESULTS: The mean age
      of patients was 19.4 +/- 6.2 months. Two patients had bilateral stones; thus,
      PCNL was performed on 34 kidney units. The mean size of the largest stone
      diameter was 17.5 +/- 7.8 mm. The mean duration of procedures was 121.52 +/-
      29.05 minutes, ranging from 60 to 180 minutes. The most common complication was
      fever (n = 9, 26.4%), and hemorrhage that needs transfusion was the second one (n
      = 4, 11.7%). Seventeen patients with complications were in the first degree of
      Clavien complication system and five of them were in the second degree.
      CONCLUSIONS: Due to our experience, utilizing PCNL with adult-sized instruments
      in management of urolithiasis in less than 3 years old children appeared to be
      effective and relatively safe.

PMID- 27716890
TI  - The removal of a stuck catheter: an alternative to Hong's technique.
AB  - The use of the tunneled central venous catheter (CVC) is steadily increasing
      worldwide as a means of vascular access for hemodialysis. The increased use of
      these devices, which often outlive the patients, and the extended time they are
      used are associated with more frequent complications. Among these, one of the
      emerging complications is that of the "embedded" or stuck catheter. This term
      refers to when the catheter cannot be removed after detaching the retention cuff.
      In medical literature, experiences with the removal of stuck catheters are
      described with the use of several different methods. Currently the most commonly
      used technique also considered the safest is "endoluminal dilation" also known as
      Hong's Technique, recently modified by Quaretti and Galli. Below, a new technique
      using a Vollmar ring is described for removing a stuck catheter as an alternative
      to Hong's technique, or after a failed attempt at using Hong's technique.

PMID- 27716889
TI  - Establishment of two data mining models of lung cancer screening based on three
      gene promoter methylations combined with telomere damage.
AB  - OBJECTIVE: To identify the significance of a support vector machine (SVM) model
      and a decision tree (DT) model for the diagnosis of lung cancer combined with the
      detection of fragile histidine triad (FHIT), RAS association domain family 1
      (RASSF1A) and cyclin-dependent kinase inhibitor 2A (p16) promoter methylation
      levels and relative telomere length (RTL) of white blood cells from peripheral
      blood DNA. METHODS: The levels of p16, RASSF1A and FHIT promoter methylation and
      the RTL of white blood cells in peripheral blood DNA of 200 healthy individuals
      and 200 lung cancer patients were analyzed by SYBR Green-based quantitative
      methylation-specific PCR and quantitative PCR. Based on the 4 biomarkers, SVM and
      DT models were developed. RESULTS: The levels of FHIT, RASSF1A and p16 promoter
      methylation were 3.33 (1.86-6.40) and 2.85 (1.39-5.44) (p = 0.002); 27.62 (9.09
      52.86) and 17.17 (3.86-50.87) (p = 0.038); and 0.59 (0.16-4.50) and 0.36 (0.06
      4.00) (p = 0.008) in cases and controls, respectively. RTL was 0.93 +/- 0.32 and
      1.16 +/- 0.57 (p<0.001). The areas under the receiver operating characteristic
      (ROC) curves of the Fisher discriminant analysis, SVM and DT models were 0.670
      (0.569-0.761), 0.810 (0.719-0.882) and 0.810 (0.719-0.882), respectively.
      CONCLUSIONS: The SVM and DT models for diagnosing lung cancer were successfully
      developed through the combined detection of p16, RASSF1A and FHIT promoter
      methylation and RTL, which provided useful tools for screening lung cancer.

PMID- 27716891
TI  - Does pre- and post-angioplasty Doppler ultrasound evaluation help in predicting
      vascular access outcome?
AB  - BACKGROUND: Kidney Disease - Improving Global Outcomes (KDIGO) recommends post
      percutaneous transluminal angioplasty (PTA) <30% residual stenosis (RS) and
      hemodynamic parameters improvement. Primary end point: how post-PTA access blood
      flow (ABF) improvement predicts vascular access (VA) outcome. Secondary: compare
      Doppler ultrasound (DU) and angiography diagnostic accuracy; determine how other
      factors predict outcome. METHODS: Eighty patients. DU evaluation performed pre-
      and post-PTA. Several parameters recorded. Secondary patency verified after 6
      months. RESULTS: Initial ABF 537 +/- 248 mL/min; final ABF 1013 +/- 354 mL/min.
      Number and location of stenosis was highly correlated between DU and angiography
      (p<0.001); central vessels mismatching. First semester overall survival was 63%;
      significantly better for fistulas (76%) than grafts (51.7%), p 0.044. Final
      RS>30% associated to better survival, p 0.038. Initial ABF<500 mL/min and
      multiple stenosis did not affect outcome (p>0.05). A >2-fold ABF increase had no
      significant impact on fistulas (p>0.05) but was significantly associated with
      worst outcomes in grafts (23.1% vs. 73.5%, p 0.009). Grafts had lower survival
      (HR 3.3, p 0.034). CONCLUSIONS: Although less accurate for central lesions, DU
      has a key role on VA surveillance, allowing a morphologic and hemodynamic
      assessment. Angioplasty is effective in preserving VA; however, it may increase
      restenosis due to accelerated neointimal hyperplasia. Current parameters are not
      useful. Trials addressing this issue are needed.

PMID- 27716892
TI  - Duplex ultrasound for the prediction of vascular events associated with
      arteriovenous fistulas in hemodialysis patients.
AB  - OBJECTIVE: To determine if duplex ultrasound (US) for arteriovenous fistulas
      (AVFs) can predict vascular events (VEs; thrombosis and stenosis). METHODS:
      Duplex US was performed for vascular access evaluation in 2557 maintenance
      hemodialysis (HD) patients between October 1, 2013 and March 31, 2016. Of these
      patients, 2184 patients were finally included in this study. AVF dysfunction was
      assessed using the brachial artery blood flow volume (Qa; mL/min), arterial blood
      flow resistance index (RI), and residual diameter of the fistula vein (RD; mm).
      Proximal, midpoint, and distal aspects of the fistulas were measured. The
      baseline measurements were the US assessments, and the endpoint was VEs requiring
      vascular access intervention therapy or vascular surgery. Associations of US
      findings and VEs were assessed with receiver operating characteristic curve
      analysis, log-rank analysis, and multivariate Cox hazard models. RESULTS: The
      mean Qa was 772.8 +/- 441.4 mL/min; RI, 0.56 +/- 0.1; and RD, 2.37 +/- 1.0 mm.
      The optimal Qa cut-off point was calculated as 581.5 mL/min, RI cut-off as 0.56,
      and RD cut-off as 1.85 mm. VEs were more frequent in patients with a Qa <581.5
      mL/min than in those with a Qa >581.5 mL/min (p<0.001). In multivariate analysis,
      Qa, ferritin, transferrin saturation, and warfarin use were significantly
      associated with VEs. CONCLUSIONS: US evaluation of AVFs in HD patients is a
      simple method to predict the risks of thrombosis and fistula dysfunction. Qa,
      ferritin, transferrin saturation, and warfarin use might be associated with VEs.

PMID- 27716893
TI  - A modified de novo insertion technique for catheter replacement in elderly
      hemodialysis patients: a single clinic retrospective analysis.
AB  - PURPOSE: For patients who rely on a tunneled cuffed catheter, replacement or
      catheter removal is typically necessary. We recently performed a modified de novo
      insertion technique for catheter replacement in our practice. As the technique
      has not yet been studied comprehensively, we performed a retrospective study to
      evaluate the safety and efficacy of de novo placed catheter without delay for
      catheter replacement in elderly hemodialysis patients. METHODS: A retrospective
      review of 164 elderly patients was conducted during a period of three years.
      There were 84 patients in study group, as well as 80 patients in a control group,
      who had catheter replacement by guidewire exchange technique. Clinical follow-up
      data was collected. RESULTS: All catheters were placed successfully. The mean
      survival time per catheter was 641 catheter days (study group) and 485 catheter
      days (control group). The primary patency rates of 30 days were 97.7% (study
      group) and 90% (control group), respectively, with statistically significant
      difference (p = 0.04). The incidence of catheter infection was not statistically
      significantly different in both groups (p = 0.586), but the case of catheter
      dysfunction was significantly lower in study group compared to control group (p =
      0.003). CONCLUSIONS: The de novo placed catheter without delay technique for
      catheter replacement near the pre-existing venotomy site is safe, and boasts
      similar infection rates with lower dysfunction rates compared to tunneled
      catheter insertion by guidewire exchange technique.

PMID- 27716894
TI  - Cognitive function may be a predictor of retinopathy progression in patients with
      type 2 diabetes.
AB  - PURPOSE: Microvascular and macrovascular complications of diabetes, such as
      retinopathy and nephropathy, progress over time and may be associated with
      cognitive decline. In this article, we aim to gain further insight into the
      association between cognitive function and retinopathy in type 2 diabetes.
      METHODS AND RESULTS: In this observational 8-year prospective study of 498
      outpatients, demographic and clinical variables were monitored, along with
      retinopathy, depression, anxiety, and cognitive function. Baseline fundus
      photographs were available in 477 patients, 240 with no retinopathy, 110 with
      mild retinopathy, and 127 with moderate/more severe retinopathy. Of the first 2
      groups, 279 patients were reevaluated after 8 years, of whom 181 still had
      no/mild retinopathy and 98 had progressed to more severe stages. On multivariate
      analysis, retinopathy progression was associated with being insulin-treated (p =
      0.036), and worse cognitive function (p = 0.025) at baseline. CONCLUSIONS:
      Cognitive function may be an independent predictor of retinopathy progression.

PMID- 27716895
TI  - The biology of germ cell tumors in disorders of sex development.
AB  - Development of a malignant germ cell tumor, i.e., germ cell cancer (GCC) in
      individuals with disorders of sex development (DSD) depends on a number of (epi
      )genetic factors related to early gonadal- and germ cell development, possibly
      related to genetic susceptibility. Fetal development of germ cells is
      orchestrated by strict processes involving specification, migration and the
      development of a proper gonadal niche. In this review we will discuss the early
      (epi-)genetic events in normal and aberrant germ cell and gonadal development.
      Focus will be on the formation of the precursor lesions of GCC in individuals who
      have DSD. In our view, expression of the different embryonic markers in, and
      epigenetic profile of the precursor lesions reflects the developmental stage in
      which these cells are blocked in their maturation. Therefore, these are not a
      primary pathogenetic driving force. Progression later in life towards a full
      blown cancer likely depends on additional factors such as a changed endocrine
      environment in a susceptible individual. Genetic susceptibility is, as evidenced
      by the presence of specific risk genetic variants (SNPs) in patients with a
      testicular GCC, related to genes involved in early germ cell and gonadal
      development.

PMID- 27716896
TI  - Choroidal abnormalities in cafe-au-lait syndromes: a new differential diagnostic
      tool?
AB  - The best known cafe-au-lait syndrome is neurofibromatosis type 1 (NF1). Legius
      syndrome (LS) is another, rarer syndrome with cafe-au-lait macules (CALMs). In
      young patients their clinical picture is often indistinguishable. We investigated
      the presence of choroidal abnormalities in syndromes with CALMs as a candidate
      tool for a more efficient diagnosis. Thirty-four patients with NF1 (14 with a
      truncating mutation, 14 with a non-truncating mutation and 6 with unknown
      mutation) and 11 patients with LS. All patients underwent an ophthalmological
      examination. Infrared images were performed. Choroidal nodules were diagnosed in
      65% of the NF1 group. About 71% of NF1 patients with a truncating mutation and
      50% of patients with a non-truncating mutation were found to have nodules.
      Choroidal nodules were seen in 18% of the LS patients, never more than one
      nodule/eye was detected in this group. Choroidal nodules are more abundantly
      present in NF1 genotypes with truncating mutations. In contrast, the number of
      choroidal nodules in LS is comparable with their presence in healthy individuals.
      Especially at an early age, when the clinical picture is incomplete, the
      detection of choroidal nodules is of diagnostic value, and helps in an
      appropriate genetic counselling and follow-up. These results support the
      suggestion to include choroidal nodules to the diagnostic criteria for NF1.

PMID- 27716897
TI  - Birth and Adoptive Parent Antisocial Behavior and Parenting: A Study of Evocative
      Gene-Environment Correlation.
AB  - Negative parenting is shaped by the genetically influenced characteristics of
      children (via evocative rGE) and by parental antisocial behavior; however, it is
      unclear how these factors jointly impact parenting. This study examined the
      effects of birth parent and adoptive parent antisocial behavior on negative
      parenting. Participants included 546 families within a prospective adoption
      study. Adoptive parent antisocial behavior emerged as a small but significant
      predictor of negative parenting at 18 months and of change in parenting from 18
      to 27 months. Birth parent antisocial behavior predicted change in adoptive
      father's (but not mother's) parenting over time. These findings highlight the
      role of parent characteristics and suggest that evocative rGE effects on
      parenting may be small in magnitude in early childhood.

PMID- 27716899
TI  - Prospective cohort study of laparoscopic and open hepatectomy for hepatocellular
      carcinoma.
AB  - BACKGROUND: The safety and feasibility of laparoscopic hepatectomy for
      hepatocellular carcinoma (HCC) with a diameter of 5 cm or less is well
      recognized. The role of laparoscopy in treating large HCC (5-10 cm) remains
      controversial. This prospective cohort study was undertaken to assess the short-
      and long-term outcomes of laparoscopic hepatectomy for large HCC and to compare
      this approach with open hepatectomy. METHODS: Patients with a solitary HCC
      (diameter 5-10 cm) who underwent open or laparoscopic hepatectomy were enrolled
      in a prospective observational study from January 2012 to April 2015.
      Perioperative and follow-up data were analysed. RESULTS: Some 128 patients
      underwent laparoscopic hepatectomy and 207 had an open hepatectomy. One and two
      perioperative deaths were reported in the laparoscopic and open groups
      respectively. Laparoscopic hepatectomy was converted to an open procedure in 12
      (9.4 per cent) of 128 patients. More patients in the laparoscopic group underwent
      an anatomical hepatectomy than in the open group (45.3 versus 21.7 per cent; P =
      0.001). The postoperative complication rate was 20.3 per cent for the
      laparoscopic group versus 35.7 per cent for the open group (P = 0.003).
      Mean(s.d.) duration of hospital stay was 11.4(3.1) and 15.8(7.7) days
      respectively (P < 0.001). One- and 3-year overall survival rates in the
      laparoscopic and open groups were 94.4 versus 93.6 per cent (P = 0.875), and 81.4
      versus 82.2 per cent (P = 0.802), respectively. One- and 3-year disease-free
      survival rates were 89.4 versus 88.7 per cent (P = 0.825), and 67.3 versus 66.7
      per cent (P = 0.902), respectively. CONCLUSION: Laparoscopic hepatectomy is safe
      and feasible for the treatment of patients with large HCC.

PMID- 27716898
TI  - Distinct patterns of cytolytic T-cell activation by different tumour cells
      revealed by Ca2+ signalling and granule mobilization.
AB  - Cancer-germline genes in both humans and mice have been shown to encode antigens
      susceptible to targeting by cytotoxic CD8 T effector cells (CTL). We analysed the
      ability of CTL to kill different tumour cell lines expressing the same cancer
      germline gene P1A (Trap1a). We previously demonstrated that CTL expressing a T
      cell receptor specific for the P1A35-43 peptide associated with H-2Ld , although
      able to induce regression of P1A-expressing P815 mastocytoma cells, were much
      less effective against P1A-expressing melanoma cells. Here, we analysed
      parameters of the in vitro interaction between P1A-specific CTL and mastocytoma
      or melanoma cells expressing similar levels of the P1A gene and of surface H-2Ld
      . The mastocytoma cells were more sensitive to cytolysis than the melanoma cells
      in vitro. Analysis by video-microscopy of early events required for target cell
      killing showed that similar patterns of increase in cytoplasmic Ca2+
      concentration ([Ca2+ ]i) were induced by both types of P1A-expressing tumour
      cells. However, the use of CTL expressing a fluorescent granzyme B (GZMB-Tom)
      showed a delay in the migration of cytotoxic granules to the tumour interaction
      site, as well as a partially deficient GZMB-Tom exocytosis in response to the
      melanoma cells. Among surface molecules possibly affecting tumour-CTL
      interactions, the mastocytoma cells were found to express intercellular adhesion
      molecule-1, the ligand for LFA-1, which was not detected on the melanoma cells.

PMID- 27716901
TI  - Play Activities Program to Relieve Chronic Pain and Enhance Functional Mobility
      and Psychological Well-Being for Frail Older Adults: A Pilot Cluster Randomized
      Controlled Trial.

PMID- 27716900
TI  - Measuring financial toxicity as a clinically relevant patient-reported outcome:
      The validation of the COmprehensive Score for financial Toxicity (COST).
AB  - BACKGROUND: Cancer and its treatment lead to increased financial distress for
      patients. To the authors' knowledge, to date, no standardized patient-reported
      outcome measure has been validated to assess this distress. METHODS: Patients
      with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were
      recruited. Financial toxicity was measured by the COmprehensive Score for
      financial Toxicity (COST) measure. The authors collected data regarding patient
      characteristics, clinical trial participation, health care use, willingness to
      discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and
      health-related quality of life (HRQOL) as measured by the Functional Assessment
      of Cancer Therapy: General (FACT-G) and the European Organization for Research
      and Treatment of Cancer (EORTC) QOL questionnaires. Test-retest reliability,
      internal consistency, and validity of the COST measure were assessed using
      standard-scale construction techniques. Associations between the resulting
      factors and other variables were assessed using multivariable analyses. RESULTS:
      A total of 375 patients with advanced cancer were approached, 233 of whom (62.1%)
      agreed to participate. The COST measure demonstrated high internal consistency
      and test-retest reliability. Factor analyses revealed a coherent, single, latent
      variable (financial toxicity). COST values were found to be correlated with
      income (correlation coefficient [r] = 0.28; P<.001), psychosocial distress (r = 
      0.26; P<.001), and HRQOL, as measured by the FACT-G (r = 0.42; P<.001) and by the
      EORTC QOL instruments (r = 0.33; P<.001). Independent factors found to be
      associated with financial toxicity were race (P = .04), employment status
      (P<.001), income (P = .003), number of inpatient admissions (P = .01), and
      psychological distress (P = .003). Willingness to discuss costs was not found to
      be associated with the degree of financial distress (P = .49). CONCLUSIONS: The
      COST measure demonstrated reliability and validity in measuring financial
      toxicity. Its correlation with HRQOL indicates that financial toxicity is a
      clinically relevant patient-centered outcome. Cancer 2017;123:476-484. (c) 2016
      American Cancer Society.

PMID- 27716902
TI  - A study of motivations and expectations of patients seen in phase 1 oncology
      clinics.
AB  - BACKGROUND: To better inform clinical practice, this study was aimed at capturing
      patients' motivations for enrolling in phase 1 trials and at quantifying their
      expectations of the benefits, risks, and commitment associated with clinical
      trials and the impact of the initial consultation on their expectations. METHODS:
      This was a single-center, prospective, quantitative study of newly referred adult
      patients considering their first phase 1 oncology trial. Participants completed
      questionnaires before they were seen and an abbreviated follow-up version after
      their consultation. RESULTS: Questionnaires were completed by 396 (99%) and 301
      (76%) before and after the clinic, respectively. Participants ranked the
      possibility of tumor shrinkage (84%) as the most important motivation for
      considering a phase 1 trial; this was followed by no alternative treatments
      (56%), their physician's recommendation (44%), and the fact that the research
      might benefit others (38%). When they were asked about the potential personal
      benefit, 43% predicted tumor shrinkage initially. After the consultation, this
      increased to 47%. Fourteen percent of patients expected a cure. When asked about
      risks, 71% of the participants expected moderate side effects. When asked about
      expectations of time commitments, a majority of patients did not anticipate
      weekly visits, although this was understood by 93% of patients after the
      consultation. Overall, patients were keen to consider trials and when asked
      before and after the consultation 72% and 84% were willing to enroll in studies,
      respectively. CONCLUSIONS: This study reports that more than 80% of patients
      enroll in early-phase clinical oncology trials motivated by the potential of a
      clinical benefit, with approximately half expecting tumor shrinkage and
      approximately a tenth anticipating a cure. The typical phase 1 response rate is
      4% to 20%, and this discrepancy exemplifies the challenges faced by patients and
      healthcare professionals during their interactions for phase 1 studies. Cancer
      2016;122:3501-3508. (c) 2016 American Cancer Society.

PMID- 27716904
TI  - Chemoprevention of basal cell carcinoma: reply from authors.

PMID- 27716903
TI  - Detection of IgE autoantibodies to BP180 and BP230 and their relationship to
      clinical features in bullous pemphigoid.
AB  - BACKGROUND: IgE autoantibodies are considered to be involved in the pathogenesis
      of bullous pemphigoid (BP), particularly inflammatory and erythematous
      phenotypes. OBJECTIVES: To develop reliable enzyme-linked immunosorbent assays
      (ELISAs) for the detection of IgE autoantibodies to both BP180 and BP230 in BP
      sera, and to compare the ELISA results with clinical features. METHODS: We used
      commercially available IgG ELISAs to develop IgE ELISAs for both BP180 and BP230.
      To determine the influence of excess amounts of IgG autoantibodies, all normal
      and BP sera were tested before and after IgG adsorption. The results of the IgE
      ELISAs were statistically compared with various ELISAs and various clinical
      parameters, including our own severity scores and BP phenotypes. RESULTS: IgG
      adsorption generally showed no changes in sensitivity and specificity for IgE
      ELISAs, although slight cross-reactivity of anti-IgE secondary antibody to IgG
      and interference of excess amounts of IgG autoantibodies to IgE reactivity were
      suggested. IgE autoantibodies to BP180 were found in 21 of 36 BP sera and IgE
      autoantibodies to BP230 were found in 18 of 36 BP sera. The results of IgG and
      IgE ELISAs for both BP180 and BP230 were well correlated. IgG and IgE anti-BP180
      antibodies correlated with disease activity but IgG and IgE anti-BP230
      autoantibodies did not. IgE anti-BP230 autoantibodies correlated with nodular
      phenotype but not erythematous phenotype. CONCLUSIONS: The results of this study
      indicated that IgE autoantibodies to both BP180 and BP230 are frequently detected
      in BP sera. IgE anti-BP180 autoantibodies seemed to be pathogenic, while an
      association between IgE autoantibodies and inflammatory BP phenotype was not
      indicated.

PMID- 27716905
TI  - The sociology of late secularization: social divisions and religiosity.
AB  - At the start of the twentieth century the religious differed from the religiously
      indifferent largely in being religious. Now they differ in a number of other
      social and demographic characteristics that reduce interaction between the two
      populations further than simple numbers would require. That some of the main
      carriers of religion are immigrants or adherents of recently imported faiths
      reinforces the sense that religion is what other people do. In the context of the
      stock of religious knowledge being depleted and religion-taken-too-seriously
      being unpopular, the narrow demographic base of the religious makes conversion
      unlikely and thus makes the reversal of secularization unlikely.

PMID- 27716906
TI  - Decreased level of interleukin-10-producing B cells in patients with pemphigus
      but not in patients with pemphigoid.
AB  - BACKGROUND: While the frequency of interleukin (IL)-10-producing B (B10) cells is
      reported to have an inverse correlation with disease activity in some human
      autoimmune diseases, the association between B10 cells and autoimmune blistering
      diseases (AIBD) has not been well evaluated. Although several phenotypes of human
      regulatory B cells have been proposed, the most appropriate one in AIBD has not
      been established. OBJECTIVE: To evaluate B10 cells in AIBD including their
      phenotypes. METHODS: Peripheral blood mononuclear cells were isolated from 39
      patients with AIBD, including 14 with pemphigus and 25 with pemphigoid, and 10
      healthy controls. We investigated the frequencies of B10 cells and CD19+ CD24hi
      CD38hi B cells using flow cytometry. RESULTS: The frequencies of B10 cells and
      CD19+ CD24hi CD38hi B cells were significantly lower and higher, respectively, in
      patients with pemphigus compared with healthy controls. Comparing patients with
      pemphigoid and healthy controls, no significant difference in the frequencies of
      B10 cells and CD19+ CD24hi CD38hi B cells was observed. B10-cell level in
      pemphigus was not associated with disease severity but inversely correlated with
      the required dose of steroid for treatment. While no significant difference in
      the frequency of IL-10-producing cells among CD19+ CD24hi CD38hi B cells was
      observed, in CD9+ and CD27- B-cell subsets it was significantly decreased in
      patients with pemphigus compared with healthy controls. CONCLUSIONS: Our results
      suggest the association of B10 cells with pemphigus but not with pemphigoid. The
      decrease in B10-cell level in pemphigus is partly caused by the lower production
      of IL-10 in CD9+ and CD27- B-cell subsets.

PMID- 27716907
TI  - A susceptibility locus for classical Hodgkin lymphoma at 8q24 near MYC/PVT1
      predicts patient outcome in two independent cohorts.

PMID- 27716908
TI  - The Effects of Distance to Dentists and Dentist Supply on Children's Use of
      Dental Care.
AB  - OBJECTIVE: To examine the effects of distance to dentists and dentist supply on
      dental services use among children with Medicaid coverage in Iowa. DATA SOURCE:
      Iowa Medicaid claims for enrolled children between 2000 and 2009. STUDY DESIGN:
      The study sample included 41,554 children (providing 158,942 child-year
      observations) who were born in Iowa between 2000 and 2006 and enrolled from birth
      in the Iowa Medicaid program. Children were followed through 2009. We used
      logistic regression to simultaneously examine the effects of distance (miles to
      nearest dentist) and county-level dentist supply on a broad range of dental
      services controlling for key confounders. Additional models only used within
      child variation over time to remove unobservable time-invariant confounders.
      PRINCIPAL FINDINGS: Distance was related to lower utilization of comprehensive
      dental exams (2 percent lower odds per 1 mile increase in distance), an effect
      that also held in models using within-child variation only. Dentist supply was
      positively related to comprehensive exams and other preventive services and
      negatively related to major dental treatments; however, these associations became
      smaller and insignificant when examining within-child changes except for other
      preventive services. CONCLUSIONS: Longer distance to dentists is a barrier for
      use of comprehensive dental exams, conditional on dentist supply.

PMID- 27716910
TI  - The management of acne vulgaris in primary care: a cohort study of consulting and
      prescribing patterns using the Clinical Practice Research Datalink.
AB  - BACKGROUND: Effective management of acne vulgaris in primary care involves
      support (usually provided over a number of consultations) and prescription of
      effective treatments. However, consulting and prescribing patterns for acne in
      primary care are not well described. OBJECTIVES: To describe the rate of primary
      care consultations and follow-up consultations; prescribing patterns, including
      overall use of acne-related medications (ARMs); and initial and follow-up
      prescription for acne vulgaris in the U.K. METHODS: U.K. primary-care acne
      consultations and prescriptions for ARMs were identified in the Clinical Practice
      Research Datalink. Annual consultation rates (between 2004 and 2013) by age and
      sex, new consultations and consultations in the subsequent year were calculated,
      along with prescribing trends - during a new consultation and over the subsequent
      90 days and year - using the number of registered patients as the denominator.
      RESULTS: Two-thirds (66.1%) of patients who had a new acne consultation had no
      further acne consultations in the subsequent year. Overall 26.7%, 24.9%, and
      23.6% and 2.8% of patients were prescribed no ARM, an oral antibiotic, a topical
      antibiotic or an oral plus topical antibiotic, respectively, during a new acne
      consultation. In total 60.1% and 38.6% of patients prescribed an ARM received no
      further ARM prescriptions in the following 90 days and 1 year, respectively,
      despite most prescriptions being for 2 months or less. Prescribing rates for
      lymecycline and topical combined clindamycin and benzoyl peroxide increased
      substantially between 2004 and 2013. There were no important changes in
      consultation rates between 2004 and 2013. CONCLUSIONS: These data suggest that
      patients with acne are receiving a suboptimal initial choice of ARMs,
      longitudinal care and prescribing.

PMID- 27716909
TI  - Clarifying the biological significance of the CHK2 K373E somatic mutation
      discovered in The Cancer Genome Atlas database.
AB  - We identified CHK2 K373E as a recurrent mutation in The Cancer Genome Atlas
      (TCGA) database. In this study, we demonstrate that the K373E mutation disrupts
      CHK2 autophosphorylation as well as kinase activity, thus leading to impairment
      of CHK2 functions in suppressing cell proliferation and promoting cell survival
      after ionizing radiation. We propose that K373E impairs p53-independent induction
      of p21WAF1/CIP1 by CHK2. Our data implicate the K373E mutation of CHK2 in
      tumorigenesis.

PMID- 27716911
TI  - Understanding the Association Between Negative Life Events and Suicidal Risk in
      College Students: Examining Self-Compassion as a Potential Mediator.
AB  - OBJECTIVE: We tested a hypothesized model consistent with the notion that self
      compassion mediates the association between negative life events and suicidal
      risk (viz., depressive symptoms and suicidal behaviors) in college students
      METHOD: The sample was comprised of 331 college students. Self-compassion facets
      (viz., self-kindness, self-judgment, common humanity, isolation, mindfulness, and
      overidentification) were used in testing for multiple mediation, controlling for
      sex. RESULTS: Common humanity, mindfulness, and overidentification were found to
      mediate the association between negative life events (NLE) and depressive
      symptoms. However, common humanity was found to be the only mediator of the
      association between NLE and suicidal behaviors. CONCLUSION: These findings
      suggest that there are specific facets of self-compassion that account for the
      association between NLE and suicidal risk in college students and that (loss of)
      common humanity plays a central role in this process.

PMID- 27716912
TI  - Cancer incidence and cancer control in Mongolia: Results from the National Cancer
      Registry 2008-12.
AB  - Mongolia has a high burden from noncommunicable diseases, with cancer now the
      second leading cause of mortality. Given the paucity of situation analyses from
      the country, this study reports cancer data based on new cases 2008-12 from the
      National Cancer Registry of Mongolia covering the entire population (2.87
      million). New cancer cases of 21,564 were diagnosed over the 5-year period, with
      a slight predominance of cases (52%) in men. Liver cancer was the leading cancer
      site in both sexes (ASRs of 114.7 and 74.6 per 100,000 males and females), and
      responsible for almost two-fifths of all cancer diagnoses, followed by cancers of
      stomach, lung and oesophagus in men and cervix, stomach and oesophagus in women.
      The cumulative risk of incidence for all cancers (27.7% and 20.8% in men and
      women, respectively) positions Mongolia above China (20.2% and 13.3%), below the
      United States (34.1% and 28.5%) and similar to Russia (26.1% and 19.1%). These
      figures shed light on the considerable magnitude of cancer in the country and the
      large fraction of cancers that can be prevented by lifestyle modifications and
      vaccine implementation. An expansion of activities of the cancer registry and the
      continued development of research are necessary steps in support of national
      cancer control planning in Mongolia.

PMID- 27716913
TI  - Relation between ultrasonic properties, rheology and baking quality for bread
      doughs of widely differing formulation.
AB  - BACKGROUND: The objective was to evaluate whether an ultrasonic reflectance
      technique has predictive capacity for breadmaking performance of doughs made
      under a wide range of formulation conditions. Two flours of contrasting dough
      strength augmented with different levels of ingredients (inulin, oil, emulsifier
      or salt) were used to produce different bread doughs with a wide range of
      properties. Breadmaking performance was evaluated by conventional large-strain
      rheological tests on the dough and by assessment of loaf quality. The ultrasound
      tests were performed with a broadband reflectance technique in the frequency
      range of 0.3-6 MHz. RESULTS: Principal component analysis showed that ultrasonic
      attenuation and phase velocity at frequencies between 0.3 and 3 MHz are good
      predictors for rheological and bread scoring characteristics. CONCLUSIONS:
      Ultrasonic parameters had predictive capacity for breadmaking performance for a
      wide range of dough formulations. Lower frequency attenuation coefficients
      correlated well with conventional quality indices of both the dough and the
      bread. (c) 2016 Society of Chemical Industry.

PMID- 27716914
TI  - Global antioxidant response of meat.
AB  - BACKGROUND: The global antioxidant response (GAR) method uses an enzymatic
      digestion to release antioxidants from foods. Owing to the importance of
      digestion for protein breakdown and subsequent release of bioactive compounds,
      the aim of the present study was to compare the GAR method for meat with the
      existing methodologies: the extraction-based method and QUENCHER. Seven fresh
      meats were analyzed using ABTS and FRAP assays. RESULTS: Our results indicated
      that the GAR of meat was higher than the total antioxidant capacity (TAC)
      assessed with the traditional extraction-based method. When evaluated with GAR,
      the thermal treatment led to an increase in the TAC of the soluble fraction,
      contrasting with a decreased TAC after cooking measured using the extraction
      based method. The effect of thermal treatment on the TAC assessed by the QUENCHER
      method seemed to be dependent on the assay applied, since results from ABTS
      differed from FRAP. CONCLUSION: Our results allow us to hypothesize that the
      activation of latent bioactive peptides along the gastrointestinal tract should
      be taken into consideration when evaluating the TAC of meat. Therefore, we
      conclude that the GAR method may be more appropriate for assessing the TAC of
      meat than the existing, most commonly used methods. (c) 2016 Society of Chemical
      Industry.

PMID- 27716915
TI  - Stricture location predicts swallowing outcomes following endoscopic rendezvous
      procedures.
AB  - OBJECTIVES/HYPOTHESIS: Complete pharyngoesophageal strictures may be encountered
      by the otolaryngologist as a consequence of radiation/chemoradiotherapy therapies
      for head and neck cancer. A combined anterograde and retrograde dilation
      procedure (rendezvous procedure) has proven to be a useful surgical intervention
      in these cases. We assess the long-term swallowing outcomes of this patient
      cohort including gastrostomy tube (G-tube) reliance, swallowing quality of life,
      and variables that contribute to improved swallowing outcomes. STUDY DESIGN:
      Retrospective chart review. METHODS: A retrospective chart review of 18
      consecutive patients treated with rendezvous procedures between April 2007 and
      May 2015 was carried out. Data were collected from chart review and follow-up
      telephone calls including demographics, surgical/postoperative course details,
      and Eating Assessment Tool (EAT-10) (swallowing quality of life) scores. RESULTS:
      The completion rate of the procedure was 83% (15 completed/3 procedures aborted).
      Average follow-up was 22 months. Thirteen of 15 (86.7%) achieved an oral diet,
      and 7/15 (46.7%) had their G-tube removed. G-tube-independent (GTI) patients had
      an average stricture length of 2.33 cm and an average distance from the incisors
      of 17.4 cm compared to G-tube dependent-(GTD) patients who had an average
      stricture length of 2.63 cm and 14.6 cm mean distance from the incisors (P = .66
      and .0343, respectively). Final EAT-10 scores averaged 20.1 in GTI patients and
      33.8 in GTD patients (P = .022). Stricture/incisor distance and EAT-10 scores
      demonstrated a moderate to strong negative correlation (r = -0.67). CONCLUSIONS:
      Following the endoscopic rendezvous procedure, swallowing outcomes and G-tube
      status is related to the distance of the stricture from the incisors. LEVEL OF
      EVIDENCE: 2b Laryngoscope, 127:1388-1391, 2017.

PMID- 27716917
TI  - The Motivating Power of Visionary Images: Effects on Motivation, Affect, and
      Behavior.
AB  - OBJECTIVE: Visionary images are identity-relevant, picture-like mental
      representations of a desirable and attainable future appearing regularly in a
      person's stream of thought. Prior research indicates that both mental and real
      images provide access to implicit motives. We therefore proposed that visionary
      images motivate people by arousing their implicit motives and tested this
      hypothesis in two experimental studies. METHOD: We used guided visualizations to
      administer motive-domain-specific visionary images (Study 1: achievement and
      neutral, Mage  = 24.4, 51 participants, 34 women; Study 2: affiliation and power,
      Mage  = 24.01, 51 participants, 28 women) to arouse the respective implicit
      motive. Motivation was measured via residual changes in affective (i.e., changes
      in affective arousal), behavioral (i.e., performance on a concentration task,
      behavioral choices in a prisoner's dilemma), and mental (i.e., motive imagery in
      the Picture Story Exercise) indicators of motivation. RESULTS: The results
      largely confirmed our hypothesis. Visionary images increased motivation in the
      targeted domain. Some effects were moderated by participants' implicit motives.
      CONCLUSIONS: The findings underscore the role of implicit motives in
      understanding the motivational effectiveness of visionary images.

PMID- 27716916
TI  - Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha1 induces a
      cardiac excitation-contraction coupling phenotype without metabolic remodelling.
AB  - KEY POINTS: Transcriptional co-activator PGC-1alpha1 has been shown to regulate
      energy metabolism and to mediate metabolic adaptations in pathological and
      physiological cardiac hypertrophy but other functional implications of PGC
      1alpha1 expression are not known. Transgenic PGC-1alpha1 overexpression within
      the physiological range in mouse heart induces purposive changes in contractile
      properties, electrophysiology and calcium signalling but does not induce
      substantial metabolic remodelling. The phenotype of the PGC-1alpha1 transgenic
      mouse heart recapitulates most of the functional modifications usually associated
      with the exercise-induced heart phenotype, but does not protect the heart against
      load-induced pathological hypertrophy. Transcriptional effects of PGC-1alpha1
      show clear dose-dependence with diverse changes in genes in circadian clock, heat
      shock, excitability, calcium signalling and contraction pathways at low
      overexpression levels, while metabolic genes are recruited at much higher PGC
      1alpha1 expression levels. These results imply that the physiological role of PGC
      1alpha1 is to promote a beneficial excitation-contraction coupling phenotype in
      the heart. ABSTRACT: The transcriptional coactivator PGC-1alpha1 has been
      identified as a central factor mediating metabolic adaptations of the heart.
      However, to what extent physiological changes in PGC-1alpha1 expression levels
      actually contribute to the functional adaptation of the heart is still mostly
      unresolved. The aim of this study was to characterize the transcriptional and
      functional effects of physiologically relevant, moderate PGC-1alpha1 expression
      in the heart. In vivo and ex vivo physiological analysis shows that expression of
      PGC-1alpha1 within a physiological range in mouse heart does not induce the
      expected metabolic alterations, but instead induces a unique excitation
      contraction (EC) coupling phenotype recapitulating features typically seen in
      physiological hypertrophy. Transcriptional screening of PGC-1alpha1
      overexpressing mouse heart and myocyte cultures with higher, acute adenovirus
      induced PGC-1alpha1 expression, highlights PGC-1alpha1 as a transcriptional
      coactivator with a number of binding partners in various pathways (such as heat
      shock factors and the circadian clock) through which it acts as a pleiotropic
      transcriptional regulator in the heart, to both augment and repress the
      expression of its target genes in a dose-dependent fashion. At low levels of
      overexpression PGC-1alpha1 elicits a diverse transcriptional response altering
      the expression state of circadian clock, heat shock, excitability, calcium
      signalling and contraction pathways, while metabolic targets of PGC-1alpha1 are
      recruited at higher PGC-1alpha1 expression levels. Together these findings
      demonstrate that PGC-1alpha1 elicits a dual effect on cardiac transcription and
      phenotype. Further, our results imply that the physiological role of PGC-1alpha1
      is to promote a beneficial EC coupling phenotype in the heart.

PMID- 27716918
TI  - Commode Cardia-Death by Valsalva Maneuver: A Case Series.
AB  - The Valsalva maneuver is used in clinical medicine for the diagnosis and/or
      treatment of various cardiovascular conditions. It can also be used in activities
      of daily living, such as defecation. Due to the cardiovascular effects produced
      during the Valsalva maneuver, it may be contraindicated in certain medical
      conditions and could be a trigger of sudden cardiac death. The incidence and
      prevalence of death following Valsalva maneuver in the presence of underlying
      cardiovascular disease, or "commode cardia," has not been examined. In 2012, the
      Wayne County Medical Examiner's Office (Detroit, MI) investigated 21 deaths that
      occurred on the toilet, fourteen of which were due to cardiovascular disease. In
      another 31 deaths in the bathroom due to cardiovascular disease, the possibility
      that the decedent defecated immediately prior to death could not be excluded.
      Hence, the incidence of commode cardia in this population ranges from 2.3 to 7.4%
      of all cardiovascular-related deaths.

PMID- 27716919
TI  - Intensive Treatment of Pediatric OCD: The Case of Sarah.
AB  - While cognitive behavior therapy (CBT) either alone or in combination with
      pharmacotherapy (e.g., selective serotonin reuptake inhibitor) has received
      strong empirical support for obsessive-compulsive disorder (OCD; Geller & March,
      2012), this treatment is often inaccessible for children and their families.
      Barriers to accessing CBT include a lack of trained therapists, clinician and
      patient beliefs about CBT, and geographical and financial barriers (Goisman et
      al., 1993; Marques et al., 2010; Turner, Heyman, Futh, & Lovell, 2009).
      Furthermore, while the majority of therapists endorse a CBT orientation, exposure
      therapy is rarely used in routine clinical practice (Whiteside, Deacon, Benito, &
      Stewart, 2016). This case study therefore describes an intensive 2- or 3-session
      treatment of childhood OCD (e.g., Farrell et al., 2016) to improve efficient and
      rapid delivery of evidence-based treatment. The case of Sarah illustrates this
      intensive treatment model and highlights clinical considerations for therapists
      when delivery a concentrated, time-limited treatment.

PMID- 27716920
TI  - Modified Cognitive Behavior Therapy for Severe, Treatment-Resistant Obsessive
      Compulsive Disorder in an Adolescent With Autism Spectrum Disorder.
AB  - There is a high rate of comorbidity between obsessive-compulsive disorder (OCD)
      and autism spectrum disorders (ASD). Standard cognitive-behavior therapy (CBT)
      protocols have been shown to be less effective in treating OCD in young people
      with ASD than in typically developing youth. This case study describes the
      treatment of an adolescent boy with severe, treatment-resistant OCD and ASD using
      a modified CBT approach. Modifications to a standard evidence-based CBT for OCD
      protocol included extended psychoeducation about anxiety; regular home-based
      sessions; and increased involvement of systems, including family and school.
      Multi-informant outcome data indicated significant improvements in OCD symptoms
      over the course of treatment with gains being maintained over a 12-month follow
      up period. These findings demonstrate the potential efficacy of modified CBT for
      pediatric OCD in the context of ASD.

PMID- 27716921
TI  - Life Events and Personality Trait Change.
AB  - OBJECTIVE: Theory and research have emphasized the impact of life events on
      personality trait change. In this article, we review prospective research on
      personality trait change in response to nine major life events in the broader
      domains of love and work. METHOD: We expected to find that life events lead to
      personality trait change to the extent that they have a lasting influence on
      individuals' thoughts, feelings, and behavior. Moreover, we predicted that love
      related life events such as marriage or parenthood would be more strongly related
      to changes in traits that emphasize affective content, whereas work-related life
      events would be more likely to lead to change in traits that reflect behavioral
      or cognitive content. RESULTS: The current state of research provided some
      evidence that life events can lead to changes in personality traits and that
      different life events may be differently related to specific trait domains.
      CONCLUSIONS: A more general conclusion emerging from this review is that the
      evidence for the nature, shape, and timing of personality trait change in
      response to life events is still preliminary. We discuss the implications of the
      results for theory and research and provide directions for future studies on life
      events and personality trait change.

PMID- 27716922
TI  - Coalescing red algae exhibit noninvasive, reversible chimerism.
AB  - Chimerism is produced by the somatic fusion of two or more genetically distinct
      conspecific individuals. In animals, the main cost of fusion is competition
      between genetically different cell lineages and the probability of original cell
      line replacement by more competitive invasive lines, which limits its natural
      frequency (3%-5%). In red and brown seaweeds, chimerism is widespread (27%-53%),
      seemingly without the negative outcomes described for animals. The rigidity of
      cell walls in macroalgae prevents cell motility and invasions. In addition, in
      moving waters, most somatic fusions involve the holdfast. Histological
      observations in laboratory-built bicolor macroalgal chimeras indicated that
      upright axes emerge from the base of plants by proliferation and vertical growth
      of discrete cell groups that include one or just a few of the cell lineages
      occurring in the holdfasts. Laboratory experiments showed growth competition
      between cell lineages, thus explaining lineage segregation during growth along
      originally chimeric erect axes. Genotyping of the axes showed more heterogeneous
      tissues basally, but apically more homogeneous ones, generating a vertical
      gradient of allele abundance and diversity. The few chimeric primary branches
      produced, eventually became homogenous after repeated branching. Therefore,
      coalescing macroagae exhibit a unique pattern of post-fusion growth, with the
      capacity to reverse chimerism. This pattern is significantly different from those
      in animals and land plants, suggesting chimerism is a biologically heterogeneous
      concept.

PMID- 27716923
TI  - Depth and temperature associations of haddock Melanogrammus aeglefinus off
      southern Newfoundland.
AB  - Using data collected as part of offshore surveys conducted during 1972-2013,
      haddock Melanogrammus aeglefinus association patterns with depth and temperature
      in southern Newfoundland waters, the northern extremity of the species' range in
      the western Atlantic Ocean, were quantified. They were typically concentrated in
      the deep warm waters along the narrow shelf slope in North-west Atlantic
      Fisheries Organization Divisions 3O and 3P with individuals moving seasonally
      into the shallow waters of the banks as they warmed. While M. aeglefinus were
      found over a range of depths and temperatures, they were primarily located at
      depths deeper and temperatures warmer than the median sampled. Analyses
      demonstrated that of the two hydrographic variables assessed, temperature was
      most influential in structuring distribution, with individuals appearing to
      change depth in order to maintain similar temperature throughout the year.
      Melanogrammus aeglefinus were found predominantly in temperatures of c. 4-8
      degrees  C which often represented some of the warmest waters available.
      Differences in fish-habitat association patterns in relation to sex or maturity
      status were not readily apparent from the analyses. Warming conditions off
      Newfoundland and Labrador in recent years might be predicted to improve local M.
      aeglefinus productivity.

PMID- 27716924
TI  - Electrophysiological activity of the pharyngoesophageal transition of total
      laryngectomees.
AB  - OBJECTIVES/HYPOTHESIS: To determine the association of the electrophysiological
      activity of the pharyngoesophageal transition with tracheoesophageal speech
      proficiency in total laryngectomees. STUDY DESIGN: An observational
      (nonexperimental) study of the correlation type with a descriptive approach.
      METHODS: Thirty-four individuals (26 males), average age 62.5 years, total
      laryngectomees rehabilitated with the use of a tracheoesophageal prosthesis, were
      assessed for tracheoesophageal speech proficiency using an adapted protocol and
      classified as good, moderate, or poor speakers. Next they were submitted to
      electromyography of the muscles of the pharyngoesophageal transition with a
      needle electrode. The area to be examined was located by videofluoroscopy.
      Electromyographic analysis was characterized as normal, neurogenic injury
      (moderate to severe, severe, severe to total), myopathic injury, or inconclusive.
      The Fisher exact test was used to determine the association between the speech
      proficiency variables and electromyography. RESULTS: in the final rating of
      tracheoesophageal speech proficiency, most laryngectomees were categorized as
      moderate (n = 24) and a few as good (n = 3). Electromyography revealed neurogenic
      injury in all laryngectomees, which was severe in most cases (n = 20), followed
      by severe to total (n = 10), and moderate to severe injury (n = 4). There was no
      significant association between he electromyographic analyses of neurogenic
      injuries and tracheoesophageal speech proficiency. CONCLUSIONS: Whether or not
      the musculature of the pharyngoesophageal transition of tracheoesophageal
      speakers had a preserved motor unit, did not prevent voice acquisition and was
      not associated with tracheoesophageal speech proficiency. However, further
      studies are needed in this area. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1369
      1375, 2017.

PMID- 27716925
TI  - Auditory brainstem implant program development.
AB  - OBJECTIVE: Auditory brainstem implants (ABIs), which have previously been used to
      restore auditory perception to deaf patients with neurofibromatosis type 2 (NF2),
      are now being utilized in other situations, including treatment of congenitally
      deaf children with cochlear malformations or cochlear nerve deficiencies.
      Concurrent with this expansion of indications, the number of centers placing and
      expressing interest in placing ABIs has proliferated. Because ABI placement
      involves posterior fossa craniotomy in order to access the site of implantation
      on the cochlear nucleus complex of the brainstem and is not without significant
      risk, we aim to highlight issues important in developing and maintaining
      successful ABI programs that would be in the best interests of patients. DATA
      SOURCES: Especially with pediatric patients, the ultimate benefits of
      implantation will be known only after years of growth and development. These
      benefits have yet to be fully elucidated and continue to be an area of
      controversy. The limited number of publications in this area were reviewed.
      REVIEW METHODS: Review of the current literature was performed. RESULTS: Disease
      processes, risk/benefit analyses, degrees of evidence, and U.S. Food and Drug
      Administration approvals differ among various categories of patients in whom
      auditory brainstem implantation could be considered for use. CONCLUSION: We
      suggest sets of criteria necessary for the development of successful and
      sustaining ABI programs, including programs for NF2 patients, postlingually
      deafened adult nonneurofibromatosis type 2 patients, and congenitally deaf
      pediatric patients. Laryngoscope, 127:1909-1915, 2017.

PMID- 27716926
TI  - Comparison of quartz crystallographic preferred orientations identified with
      optical fabric analysis, electron backscatter and neutron diffraction techniques.
AB  - Three techniques are used to measure crystallographic preferred orientations
      (CPO) in a naturally deformed quartz mylonite: transmitted light cross-polarized
      microscopy using an automated fabric analyser, electron backscatter diffraction
      (EBSD) and neutron diffraction. Pole figure densities attributable to crystal
      plastic deformation are variably recognizable across the techniques, particularly
      between fabric analyser and diffraction instruments. Although fabric analyser
      techniques offer rapid acquisition with minimal sample preparation, difficulties
      may exist when gathering orientation data parallel with the incident beam.
      Overall, we have found that EBSD and fabric analyser techniques are best suited
      for studying CPO distributions at the grain scale, where individual orientations
      can be linked to their source grain or nearest neighbours. Neutron diffraction
      serves as the best qualitative and quantitative means of estimating the bulk CPO,
      due to its three-dimensional data acquisition, greater sample area coverage, and
      larger sample size. However, a number of sampling methods can be applied to FA
      and EBSD data to make similar approximations.

PMID- 27716927
TI  - Genetics of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, also referred to as Mullerian
      agenesis, is the second most common cause of primary amenorrhea. It is
      characterized by congenital absence of the uterus, cervix, and the upper part of
      the vagina in otherwise phenotypically normal 46,XX females. MRKH syndrome has an
      incidence of about 1 in 4,500-5,000 newborn females and it is generally divided
      into two subtypes: MRKH type 1, in which only the upper vagina, cervix and the
      uterus are affected, and MRKH type 2, which is associated with additional
      malformations generally affecting the renal and skeletal systems, and also
      includes MURCS (MUllerian Renal Cervical Somite) characterized by cervico
      thoracic defects. MRKH syndrome is mainly sporadic; however, familial cases have
      been described indicating that, at least in a subset of patients, MRKH may be an
      inherited disorder. The syndrome appears to demonstrate an autosomal dominant
      inheritance pattern, with incomplete penetrance and variable expressivity. The
      etiology of MRKH syndrome is still largely unknown, probably because of its
      intrinsic heterogeneity. Several candidate causative genes have been
      investigated, but to date only WNT4 has been associated with MRKH with
      hyperandrogenism. This review summarizes and discusses the clinical features and
      details progress to date in understanding the genetics of MRKH syndrome.

PMID- 27716928
TI  - Direct and indirect influence of sulfur availability on phytoplankton
      evolutionary trajectories.
AB  - The sulfate facilitation hypothesis suggests that changes in ocean sulfate
      concentration influenced the rise to dominance of phytoplankton species of the
      red lineage. The mechanistic reasons for this phenomenon are not yet understood.
      We started to address this question by investigating the differences in S
      utilization by algae of the green and red lineages and in cyanobacteria cultured
      in the presence of either 5 mmol . L-1 (approximately equivalent to Paleozoic
      ocean concentrations) or 30 mmol . L-1 (corresponding to post-Mesozoic/extant
      concentrations) sulfate. The activities of the main enzymes involved in SO42-
      assimilation changed in response to changes in growth sulfate concentration. ATP
      sulfurylase showed different kinetics in the various taxa, with an especially odd
      behavior for the dinoflagellate. Sulfate availability had a modest effect on cell
      organic composition. Species-specific differences in the use of some elements
      were instead obvious in algae grown in the presence of different sulfate
      concentrations, overall confirming that algae of the red lineage do better at
      high sulfate than algae of the green lineage. The increase in sulfate
      concentration may thus have had an impact on phytoplankton radiation both through
      changes in their enzymatic machinery and through indirect repercussion on
      elemental usage.

PMID- 27716929
TI  - RSL class I genes positively regulate root hair development in Oryza sativa.
AB  - Root hairs are filamentous protuberances from superficial cells of plant roots
      that are critical for nutrient uptake. Genes encoding ROOT HAIR DEFECTIVE-SIX
      LIKE (RSL) class I basic helix-loop-helix proteins are expressed in future root
      hair cells (trichoblasts) of the Arabidopsis thaliana root where they positively
      regulate root hair cell development. We characterized the function of class I
      genes in Oryza sativa root development. We show that there are three RSL class I
      genes in O. sativa and that each is expressed in developing root hair cells.
      Reduction of RSL class I function results in the development of shorter root
      hairs than in wild-type. Ectopic overexpression results in the development of
      ectopic root hair cells. These data suggest that expression of individual RSL
      class I proteins is sufficient for root hair development in the cereal O. sativa
      (rice). Therefore RSL class I genes have been conserved since O. sativa and A.
      thaliana last shared a common ancestor. However, given that RSL class I genes are
      not sufficient for root hair development in A. thaliana, it suggests that there
      are differences in the mechanisms repressing RSL class I gene activity between
      members of the Poaceae and Brassicaceae.

PMID- 27716931
TI  - Compositional mapping of bitumen using local electrostatic force interactions in
      atomic force microscopy.
AB  - In recent years, many researchers have investigated bitumen surface morphology,
      especially the so-called bee-like structures, in an attempt to relate the
      chemical composition and molecular conformation to bitumen micromechanics and
      ultimately performance properties. Even though recent studies related surface
      morphology and its evolution to stiffness and stress localization, the complex
      chemical nature of bitumen and its time- and temperature-dependent properties
      still engender significant questions about the nature and origin of the observed
      morphological features and how they evolve due to exposure to various
      environmental and loading conditions. One such question is whether the observed
      surface features are formed from wax or from the coprecipitation of wax and
      asphaltene. Our prior work was mainly theoretical; it used density functional
      theory and showed that the coprecipitation theory may not stand, mainly because
      wax-asphaltene interactions are not thermodynamically favourable compared to wax
      wax interactions. This paper presents a comprehensive approach based on
      experiments to study surface morphology of bitumen and conduct compositional
      mapping to shed light on the origin of the bee-like surface morphological
      features. We used Atomic Force Microscopy (AFM), with the main focus being on
      single-pass detection and mapping of local electric properties, as a novel
      approach to enhance existing compositional mapping techniques. This method was
      found to be highly effective in differentiating various domains with respect to
      their polarity. The results of our study favour the hypothesis that the bee-like
      features are mainly composed of wax, including a variety of alkanes.

PMID- 27716930
TI  - Self-reported historic human immunodeficiency virus (HIV) testing in a Brazilian
      blood donor HIV case-control study.
AB  - BACKGROUND: There has been increased worldwide emphasis on the many benefits of
      human immunodeficiency virus (HIV) serostatus awareness for both infection
      prevention and improved treatment outcomes. Previous studies indicate that donors
      may use blood donation to be tested; the objectives of this analysis were to
      assess, among donors with previously undisclosed risk behavior in the 12 months
      before donation, the frequency of those who have previously been tested for HIV
      and the demographic and behavioral factors associated with such testing. STUDY
      DESIGN AND METHODS: In this secondary analysis from an HIV case-control study of
      blood donors in Brazil, we analyzed the response to the question, "Other than
      blood donation, have you ever been tested for HIV?" Demographic and disclosed
      risk behaviors associated with previous testing were determined. RESULTS: The
      study included 341 HIV-positive cases and 791 HIV-negative controls (1:2
      case/control ratio). Overall, 31% of blood donors (40% of cases and 26% of
      controls) reported having been tested for HIV outside of blood donation. History
      of HIV testing varied according to sex, HIV status, and reported sexual risk
      behavior. CONCLUSION: Although it is encouraging that previous testing was more
      frequent in donors with acknowledged sexual risk behavior in Brazil, 60% still
      had not been tested for HIV outside of the blood donation setting. Educating
      donors on the importance of not using blood centers as a means to get tested for
      HIV in Brazil, especially if they engage in higher risk behaviors, and seeking
      alternate testing venues instead could improve the safety of donated blood.

PMID- 27716932
TI  - Bayley-III: Cultural differences and language scale validity in a Danish sample.
AB  - The purpose of this study was to investigate cultural differences between Danish
      and American children at 2 and 3 years as measured with the developmental test
      Bayley-III, and to investigate the Bayley-III Language Scale validity. The Danish
      children (N = 43) were tested with the Bayley-III and their parents completed an
      additional language questionnaire (the MacArthur-Bates CDI). Results showed that
      scores from the Danish children did not differ significantly from the American
      norms on the Cognitive or Motor Scale, but the Danish sample scored significantly
      higher on the Language Scale. A comparison of the Bayley-III Language subtests
      with the CDI showed that the two measures correlated significantly, but the
      percentile score from the CDI was significantly higher than the percentile score
      from the Bayley-III Language subtests. This could be because the two instruments
      measure slightly different areas of language development, or because the Bayley
      III overestimates language development in Danish children. However, due to the
      limitations of the current study, further research is needed to clarify this
      issue.

PMID- 27716933
TI  - Solanum tuberosum StCDPK1 is regulated by miR390 at the posttranscriptional level
      and phosphorylates the auxin efflux carrier StPIN4 in vitro, a potential
      downstream target in potato development.
AB  - Among many factors that regulate potato tuberization, calcium and calcium
      dependent protein kinases (CDPKs) play an important role. CDPK activity increases
      at the onset of tuber formation with StCDPK1 expression being strongly induced in
      swollen stolons. However, not much is known about the transcriptional and
      posttranscriptional regulation of StCDPK1 or its downstream targets in potato
      development. To elucidate further, we analyzed its expression in different
      tissues and stages of the life cycle. Histochemical analysis of StCDPK1::GUS
      (beta-glucuronidase) plants demonstrated that StCDPK1 is strongly associated with
      the vascular system in stems, roots, during stolon to tuber transition, and in
      tuber sprouts. In agreement with the observed GUS profile, we found specific cis
      acting elements in StCDPK1 promoter. In silico analysis predicted miR390 to be a
      putative posttranscriptional regulator of StCDPK1. Quantitative real time
      polymerase chain reaction (qRT-PCR) analysis showed ubiquitous expression of
      StCDPK1 in different tissues which correlated well with Western blot data except
      in leaves. On the contrary, miR390 expression exhibited an inverse pattern in
      leaves and tuber eyes suggesting a possible regulation of StCDPK1 by miR390. This
      was further confirmed by Agrobacterium co-infiltration assays. In addition, in
      vitro assays showed that recombinant StCDPK1-6xHis was able to phosphorylate the
      hydrophilic loop of the auxin efflux carrier StPIN4. Altogether, these results
      indicate that StCDPK1 expression is varied in a tissue-specific manner having
      significant expression in vasculature and in tuber eyes; is regulated by miR390
      at posttranscriptional level and suggest that StPIN4 could be one of its
      downstream targets revealing the overall role of this kinase in potato
      development.

PMID- 27716934
TI  - Patching it together: epicutaneous vaccination with heat-labile Escherichia coli
      toxin against birch pollen allergy.

PMID- 27716935
TI  - Connecting the plant vasculature to friend or foe.
AB  - Contents 1611 I. 1611 II. 1612 III. 1612 IV. 1614 V. 1614 VI. 1614 VII. 1615
      VIII. 1616 1616 References 1616 SUMMARY: The plant vasculature transports water,
      sugars, hormones, RNAs and proteins. Such critical functions need to be protected
      from attack by pests and pathogens or from damage by wounding. Plants have
      developed mechanisms to repair vasculature when such protections fail and to even
      initiate new vascular connections to tissues supporting symbionts. The
      developmental phenomena underlying vascular repair and rewiring are therefore
      critical for horticultural grafting, for plant infection and for mutualist
      associations with rhizosphere microbes. Despite the biological and economic
      interest, we are only beginning to understand how plants connect and reconnect
      their vasculature to a wide variety of organisms. Here, I discuss recent work and
      future prospects for this emerging field.

PMID- 27716937
TI  - Low levels of strigolactones in roots as a component of the systemic signal of
      drought stress in tomato.
AB  - Strigolactones (SL) contribute to drought acclimatization in shoots, because SL
      depleted plants are hypersensitive to drought due to stomatal hyposensitivity to
      abscisic acid (ABA). However, under drought, SL biosynthesis is repressed in
      roots, suggesting organ specificity in their metabolism and role. Because SL can
      be transported acropetally, such a drop may also affect shoots, as a systemic
      indication of stress. We investigated this hypothesis by analysing molecularly
      and physiologically wild-type (WT) tomato (Solanum lycopersicum) scions grafted
      onto SL-depleted rootstocks, compared with self-grafted WT and SL-depleted
      genotypes, during a drought time-course. Shoots receiving few SL from the roots
      behaved as if under mild stress even if irrigated. Their stomata were
      hypersensitive to ABA (likely via a localized enhancement of SL synthesis in
      shoots). Exogenous SL also enhanced stomata sensitivity to ABA. As the partial
      shift of SL synthesis from roots to shoots mimics what happens under drought, a
      reduction of root-produced SL might represent a systemic signal unlinked from
      shootward ABA translocation, and sufficient to prime the plant for better stress
      avoidance.

PMID- 27716936
TI  - Integration of light and circadian signals that regulate chloroplast
      transcription by a nuclear-encoded sigma factor.
AB  - We investigated the signalling pathways that regulate chloroplast transcription
      in response to environmental signals. One mechanism controlling plastid
      transcription involves nuclear-encoded sigma subunits of plastid-encoded plastid
      RNA polymerase. Transcripts encoding the sigma factor SIG5 are regulated by light
      and the circadian clock. However, the extent to which a chloroplast target of
      SIG5 is regulated by light-induced changes in SIG5 expression is unknown.
      Moreover, the photoreceptor signalling pathways underlying the circadian
      regulation of chloroplast transcription by SIG5 are unidentified. We monitored
      the regulation of chloroplast transcription in photoreceptor and sigma factor
      mutants under controlled light regimes in Arabidopsis thaliana. We established
      that a chloroplast transcriptional response to light intensity was mediated by
      SIG5; a chloroplast transcriptional response to the relative proportions of red
      and far red light was regulated by SIG5 through phytochrome and photosynthetic
      signals; and the circadian regulation of chloroplast transcription by SIG5 was
      predominantly dependent on blue light and cryptochrome. Our experiments reveal
      the extensive integration of signals concerning the light environment by a single
      sigma factor to regulate chloroplast transcription. This may originate from an
      evolutionarily ancient mechanism that protects photosynthetic bacteria from high
      light stress, which subsequently became integrated with higher plant
      phototransduction networks.

PMID- 27716938
TI  - Nanostructured Polymeric Micelles Carrying Xanthene Dyes for Photodynamic
      Evaluation.
AB  - It was evaluated the properties of the xanthene dyes Erythrosin B, Eosin Y and
      theirs Methyl, Butyl and Decyl ester derivatives as possible photosensitizers
      (PS) for photodynamic treatments. The more hydrophobic dyes self-aggregate in
      water/ethanol solutions above 70% water (vol/vol) in the mixture. In buffered
      water, these PS were encapsulated in Pluronic polymeric surfactants of P-123 and
      F-127 by two methodologies: direct addition and the thin-film solid dispersion
      methods. The thin-film solid method provided formulations with higher stabilities
      besides effective encapsulation of the PS as monomers. Size measurements
      demonstrated that Pluronic forms self-assembled micelles with uniform size, which
      present slightly negative surface potential and a spherical form detected by TEM
      microscopy. The ester length modulates xanthene localization in the micelle,
      which is deeper with the increase in the alkyl chain. Moreover, some PS are
      distributed into two populations: one on the corona micelle interface shell (PEO
      layer) and the other into the core (PPO region). Although all PS formulations
      show high singlet oxygen quantum yield, promising results were obtained for
      Erythrosin B esters with the hydrophobic P-123, which ensures their potential as
      drug for clinical photodynamic applications.

PMID- 27716939
TI  - Tibetan Firefly Luciferase with Low Temperature Adaptation.
AB  - Fireflies are widespread all over the world and a numerous numbers of luciferases
      have been isolated and characterized. In this study, we identified and
      characterized the luciferase and luciferase-like genes from a Tibetan firefly
      collected in Shangri-La, China. The altitude of this area is more than 3300 m. We
      saw this Tibetan firefly flying with strong luminescence after sunset at ~10
      degrees C. We analyzed the transcriptome of Tibetan firefly using head, thorax,
      abdomen (without light organ), and light organ tissue by RNA sequencing. We
      identified one luciferase gene, which was almost identical to luciferase from
      fireflies Pyrocoelia species, and expressed specifically in the light organ.
      Interestingly, the optimal temperature of the Tibetan firefly recombinant
      luciferase was 10 degrees C. The Km for D-luciferin and ATP of the recombinant
      luciferase was 23 and 154 MUm, respectively. The optimal pH was around 7.0-7.5.
      The emission peak was 556 nm at pH 8.0, while it shifted to 606 nm at pH 6.0. We
      also found a luciferase-like gene with 43% identical amino acids to the Tibetan
      firefly luciferase, which was scarcely expressed in any portion of the adult
      body. No luciferase activity was detected for this luciferase-like protein.

PMID- 27716940
TI  - Dark-induced leaf senescence: new insights into a complex light-dependent
      regulatory pathway.
AB  - 563 I. 563 II. 564 III. 564 IV. 565 V. 565 VI. 567 VII. 567 568 References 568
      SUMMARY: Leaf senescence - the coordinated, active process leading to the
      organized dismantling of cellular components to remobilize resources - is a
      fundamental aspect of plant life. Its tight regulation is essential for plant
      fitness and has crucial implications for the optimization of plant productivity
      and storage properties. Various investigations have shown light deprivation and
      light perception via phytochromes as key elements modulating senescence. However,
      the signalling pathways linking light deprivation and actual senescence processes
      have long remained obscure. Recent analyses have demonstrated that PHYTOCHROME
      INTERACTING FACTORS (PIFs) are major transcription factors orchestrating dark
      induced senescence (DIS) by targeting chloroplast maintenance, chlorophyll
      metabolism, hormone signalling and production, and the expression of senescence
      master regulators, uncovering potential molecular links to the energy deprivation
      signalling pathway. PIF-dependent feed-forward regulatory modules might be of
      critical importance for the highly complex and initially light-reversible DIS
      induction.

PMID- 27716941
TI  - Photobiomodulation by Infrared Diode Laser: Effects on Intracellular Calcium
      Concentration and Nitric Oxide Production of Paramecium.
AB  - In Paramecium, cilia beating is correlated to intracellular calcium concentration
      ([Ca2+ ]i) and nitric oxide (NO) synthesis. Recent findings affirm that
      photobiomodulation (PBM) can transiently increase the [Ca2+ ]i in mammalian
      cells. In this study, we investigated the effect of both 808 and 980 nm diode
      laser irradiated with flat-top hand-piece on [Ca2+ ]i and NO production of
      Paramecium primaurelia, to provide basic information for the development of new
      therapeutic approaches. In the experiments, the laser power in CW varied (0.1;
      0.5; 1; and 1.5 W) to generate the following respective fluences: 6.4; 32; 64;
      and 96 J cm-2 . The 6.4 J cm-2 did not induce PBM if irradiated by both 808 and
      980 nm diode laser. Conversely, the 32 J cm-2 fluence had no effect on Paramecium
      cells if irradiated by the 808 nm laser, while if irradiated by the 980 nm laser
      induced increment in swimming speed (suggesting an effect on the [Ca2+ ]i, NO
      production, similar to the 64 J cm-2 with the 808 nm wavelength). The more
      evident discordance occurred with the 96 J cm-2 fluence, which had the more
      efficient effect on PBM among the parameters if irradiated with the 808 nm laser
      and killed the Paramecium cells if irradiated by the 980 nm laser. Lastly, the
      980 nm and 64 or 96 J cm-2 were the only parameters to induce a release of stored
      calcium.

PMID- 27716942
TI  - An assay for entry of secreted fungal effectors into plant cells.
AB  - Successful colonization of plants by prokaryotic and eukaryotic pathogens
      requires active effector-mediated suppression of defense responses and host
      tissue reprogramming. Secreted effector proteins can either display their
      activity in the apoplast or translocate into host cells and function therein.
      Although characterized in bacteria, the molecular mechanisms of effector delivery
      by fungal phytopathogens remain elusive. Here we report the establishment of an
      assay that is based on biotinylation of effectors in the host cytoplasm as
      hallmark of uptake. The assay exploits the ability of the bacterial biotin ligase
      BirA to biotinylate any protein that carries a short peptide (Avitag). It is
      based on the stable expression of BirA in the cytoplasm of maize plants and on
      engineering of Ustilago maydis strains to secrete Avitagged effectors. We
      demonstrate translocation of a number of effectors in the U. maydis-maize system
      and show data that suggest that the uptake mechanism could be rather nonspecific
      The assay promises to be a powerful tool for the classification of effectors as
      well as for the functional study of effector uptake mechanism not only in the
      chosen system but more generally for systems where biotrophic interactions are
      established.

PMID- 27716943
TI  - Paracetamol (acetaminophen) for prevention or treatment of pain in newborns.
AB  - BACKGROUND: Newborn infants have the ability to experience pain. Hospitalised
      infants are exposed to numerous painful procedures. Healthy newborns are exposed
      to pain if the birth process consists of assisted vaginal birth by vacuum
      extraction or by forceps and during blood sampling for newborn screening tests.
      OBJECTIVES: To determine the efficacy and safety of paracetamol for the
      prevention or treatment of procedural/postoperative pain or pain associated with
      clinical conditions in neonates. To review the effects of various doses and
      routes of administration (enteral, intravenous or rectal) of paracetamol for the
      prevention or treatment of pain in neonates. SEARCH METHODS: We used the standard
      search strategy of the Cochrane Neonatal Review group to search the Cochrane
      Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed
      (1966 to 9 May 2016), Embase (1980 to 9 May 2016), and CINAHL (1982 to 9 May
      2016). We searched clinical trials' databases, Google Scholar, conference
      proceedings, and the reference lists of retrieved articles. SELECTION CRITERIA:
      We included randomised and quasi-randomised controlled trials of paracetamol for
      the prevention/treatment of pain in neonates (<= 28 days of age). DATA COLLECTION
      AND ANALYSIS: Two review authors independently extracted data from the articles
      using pre-designed forms. We used this form to decide trial inclusion/exclusion,
      to extract data from eligible trials and to request additional published
      information from authors of the original reports. We entered and cross-checked
      data using RevMan 5 software. When noted, we resolved differences by mutual
      discussion and consensus. We used the GRADE approach to assess the quality of
      evidence. MAIN RESULTS: We included nine trials with low risk of bias, which
      assessed paracetamol for the treatment of pain in 728 infants. Painful procedures
      studied included heel lance, assisted vaginal birth, eye examination for
      retinopathy of prematurity assessment and postoperative care. Results of
      individual studies could not be combined in meta-analyses as the painful
      conditions, the use of paracetamol and comparison interventions and the outcome
      measures differed. Paracetamol compared with water, cherry elixir or EMLA cream
      (eutectic mixture of lidocaine and prilocaine) did not significantly reduce pain
      following heel lance. The Premature Infant Pain Profile score (PIPP) within three
      minutes following lancing was higher in the paracetamol group than in the oral
      glucose group (mean difference (MD) 2.21, 95% confidence interval (CI) 0.72 to
      3.70; one study, 38 infants). Paracetamol did not reduce "modified facies scores"
      after assisted vaginal birth (one study, 119 infants). In another study (n =
      123), the Echelle de Douleur et d'Inconfort du Nouveau-Ne score at two hours of
      age was significantly higher in the group that received paracetamol suppositories
      than in the placebo suppositories group (MD 1.00, 95% CI 0.60 to 1.40). In that
      study, when infants were subjected to a heel lance at two to three days of age,
      Bernese Pain Scale for Neonates scores were higher in the paracetamol group than
      in the placebo group, and infants spent a longer time crying (MD 19 seconds, 95%
      CI 14 to 24). For eye examinations, no significant reduction in PIPP scores in
      the first or last 45 seconds of eye examination was reported, nor at five minutes
      after the eye examination. In one study (n = 81), the PIPP score was
      significantly higher in the paracetamol group than in the 24% sucrose group (MD
      3.90, 95% CI 2.92 to 4.88). In one study (n = 114) the PIPP score during eye
      examination was significantly lower in the paracetamol group than in the water
      group (MD -2.70, 95% CI -3.55 to 1.85). For postoperative care following major
      surgery, the total amount of morphine (ug/kg) administered over 48 hours was
      significantly less among infants assigned to the paracetamol group than to the
      morphine group (MD -157 ug/kg, 95% CI -27 to -288). No adverse events were noted
      in any study. The quality of evidence according to GRADE was low. AUTHORS'
      CONCLUSIONS: The paucity and low quality of existing data do not provide
      sufficient evidence to establish the role of paracetamol in reducing the effects
      of painful procedures in neonates. Paracetamol given after assisted vaginal birth
      may increase the response to later painful exposures. Paracetamol may reduce the
      total need for morphine following major surgery, and for this aspect of
      paracetamol use, further research is needed.

PMID- 27716944
TI  - MdMyb93 is a regulator of suberin deposition in russeted apple fruit skins.
AB  - A comparison of the transcriptomes of russeted vs nonrusseted apple skins
      previously highlighted a tight relationship between a gene encoding an MYB-type
      transcription factor, MdMYB93, and some key suberin biosynthetic genes. The
      present work assesses the role of this transcription factor in the suberization
      process. A phylogenetic analysis of MdMYB93 and Arabidopsis thaliana MYBs was
      performed and the function of MdMYB93 was further investigated using
      Agrobacterium-mediated transient overexpression in Nicotiana benthamiana leaves.
      An RNA-Seq analysis was performed to highlight the MdMYB93-regulated genes.
      Ultraperformance liquid chromatography-triple time-of-flight (UPLC-TripleTOF) and
      GC-MS were used to investigate alterations in phenylpropanoid, soluble-free lipid
      and lipid polyester contents. A massive accumulation of suberin and its
      biosynthetic precursors in MdMYB93 agroinfiltrated leaves was accompanied by a
      remobilization of phenylpropanoids and an increased amount of lignin precursors.
      Gene expression profiling displayed a concomitant alteration of lipid and
      phenylpropanoid metabolism, cell wall development, and extracellular transport,
      with a large number of induced transcripts predicted to be involved in suberin
      deposition. The present work supports a major role of MdMYB93 in the regulation
      of suberin deposition in russeted apple skins, from the synthesis of monomeric
      precursors, their transport, polymerization, and final deposition as suberin in
      primary cell wall.

PMID- 27716945
TI  - The effects of animal age, feeding regime and a dietary beta-agonist on
      tenderness of three beef muscles.
AB  - BACKGROUND: Animal age as determined by number of permanent incisors (p. i.) is
      used in classification of beef carcasses to describe expected meat tenderness.
      However, animals differing in age are reared under different production systems
      (pasture or feedlot). In addition to age, other factors associated with
      particular production systems may also influence the palatability of meat.
      Therefore, the effects of age combined with feeding regime and the
      supplementation of a beta-agonist (zilpaterol) on the tenderness of M.
      longissimus lumborum (LL), M. semitendinosus (ST) and M. biceps femoris (BF)
      muscles were investigated. RESULTS: Tenderness of LL cuts was least affected by
      age but zilpaterol significantly decreased tenderness and ageing potential.
      Tenderness of high-collagen cuts (BF and ST) was negatively affected by age due
      to reduced collagen solubility. The effect of zilpaterol on these cuts was less
      significant and BF and ST cuts of the grain-fed A-age animals (0 p. i.)
      supplemented with zilpaterol (AZ) were more tender than the same cuts of grass
      fed animals with 1-2 p. i. (AB-age) and grass-fed animals with 3-6 p. i. (B-age)
      according to Warner-Bratzler shear force (WBSF) and sensory analysis for
      tenderness. CONCLUSION: This study indicates that beta-agonists may influence
      variation in tenderness within an age class more than age or feeding regime. (c)
      2016 Society of Chemical Industry.

PMID- 27716946
TI  - New opportunities and challenges in the assessment of drugs for atopic diseases.
AB  - Atopic conditions (atopic dermatitis, rhinitis, and asthma) belong to the most
      common noncommunicable diseases and are driven by chronic inflammatory reactions.
      They have a strong impact on the quality of life and represent a substantial and
      growing socio-economic burden. Interestingly, there is an increasing interest in
      the development of new therapeutic options with a number of biologics and small
      molecules targeting potential key mechanisms in atopic conditions. However,
      besides the safety issue, most of the new active substances are still evaluated
      according to the traditional efficacy paradigm focusing on the success in
      treating exacerbations and flares. Instead, the future approaches in drug
      development and assessment should rather concentrate on the long-term control of
      these diseases and consider their potential as disease-modifying strategies in
      the era of precision medicine. To reach this goal, a number of unsolved issues
      have to be addressed and consensually accepted by the stakeholders in this field.
      Thus, a successful and rapid development of new treatments requests a paradigm
      shift and a new way of thinking in the mind of physicians, pharmaceutical
      industry, regulators, and HTAs. This seems mandatory in order to optimize drug
      development and to facilitate the accessibility of new therapies to the growing
      population of patients suffering from atopic conditions on a global level.

PMID- 27716947
TI  - Parasites, microbiota and metabolic disease.
AB  - Recent years have witnessed a dramatic increase in diseases that are ascribed to
      alter metabolism eventually resulting in conditions including obesity, type-2
      diabetes (T2D), cardiovascular disease and metabolic syndrome (MetS). Of the many
      factors to which this rise has been attributed, including diet, physical activity
      and inflammation, several studies have correlated these disease states with
      alterations in gut microbiota. Simultaneously, studies have demonstrated the
      ability of parasites to alter microbial communities within their shared niche,
      leading to alterations in inflammatory processes. However, very few reports have
      addressed how these changes to the microbiome may be a mechanism by which
      parasites influence not only inflammation but also metabolic states. In this
      review, we attempt to draw parallels between the three capacious topics and
      examine the interrelationship between them.

PMID- 27716948
TI  - Direct oral anticoagulants in patients with atrial fibrillation and renal
      impairment, extremes in weight, or advanced age.
AB  - A growing number of patients with an indication for stroke prevention in atrial
      fibrillation have kidney-, age-, or weight-related alterations in
      pharmacokinetics that affect dosing of direct oral anticoagulants. Because these
      patients were excluded from or comprised a small number of patients in clinical
      trials, there is a lack of evidence to guide clinicians. As a consequence, many
      patients do not receive oral anticoagulation despite a high risk for atrial
      fibrillation-related stroke. Here, we present a review of direct oral
      anticoagulant pharmacokinetics and a review of the available clinical evidence in
      patients with weight-, kidney-, and age-related disease.

PMID- 27716949
TI  - Skin Exposure to Ultraviolet B Rapidly Activates Systemic Neuroendocrine and
      Immunosuppressive Responses.
AB  - The back skin of C57BL/6 mice was exposed to a single 400 mJ cm-2 dose of
      ultraviolet B (UVB), and parameters of hypothalamic-pituitary-adrenal (HPA) axis
      in relation to immune activity were tested after 30-90 min following irradiation.
      Levels of brain and/or plasma corticotropin-releasing hormone (CRH), beta
      endorphin, ACTH and corticosterone (CORT) were enhanced by UVB. Hypophysectomy
      had no effect on UVB-induced increases of CORT. Mitogen-induced IFNgamma
      production by splenocytes from UVB-treated mice was inhibited at 30, 90 min and
      after 24 h. UVB also led to inhibition of IL-10 production indicating an
      immunosuppressive effect on both Th1 and Th2 cytokines. Conditioned media from
      splenocytes isolated from UVB-treated animals had no effect on IFNgamma
      production in cultured normal splenocytes; however, IFNgamma increased with
      conditioned media from sham-irradiated animals. Sera from UVB-treated mice
      suppressed T-cell mitogen-induced IFNgamma production as compared to sera from
      sham-treated mice. IFNgamma production was inhibited in splenocytes isolated from
      UVB-treated animals with intact pituitary, while stimulated in splenocytes from
      UVB-treated hypophysectomized mice. Thus, cutaneous exposure to UVB rapidly
      stimulates systemic CRH, ACTH, beta-endorphin and CORT production accompanied by
      rapid immunosuppressive effects in splenocytes that appear to be independent of
      the HPA axis.

PMID- 27716951
TI  - Treatment of a Child With Obsessive-Compulsive Disorder With Limited Motivation:
      Course and Outcome of Cognitive-Behavior Therapy.
AB  - Motivation is a key ingredient in the successful treatment of pediatric obsessive
      compulsive disorder (OCD). As a first-line treatment, cognitive-behavior therapy
      (CBT) requires extensive client engagement, including participating in exposures
      and doing homework tasks. A lack of motivation to comply with these tasks may
      seriously affect treatment outcome. This case study identifies factors
      interfering with motivation and illustrates motivational strategies to enhance
      compliance of a child with OCD. The patient was an 11-year-old boy with severe
      OCD and symptoms of oppositional defiant disorder (ODD). He had extensive OCD
      related avoidance behavior but denied the presence of symptoms or did not
      acknowledge them as a problem. In this article, we discuss the different
      techniques used to enhance motivation, which subsequently led to a favorable
      outcome.

PMID- 27716950
TI  - Fungal diversity and seasonal succession in ash leaves infected by the invasive
      ascomycete Hymenoscyphus fraxineus.
AB  - High biodiversity is regarded as a barrier against biological invasions. We
      hypothesized that the invasion success of the pathogenic ascomycete Hymenoscyphus
      fraxineus threatening common ash in Europe relates to differences in dispersal
      and colonization success between the invader and the diverse native competitors.
      Ash leaf mycobiome was monitored by high-throughput sequencing of the fungal
      internal transcribed spacer region (ITS) and quantitative PCR profiling of H.
      fraxineus DNA. Initiation of ascospore production by H. fraxineus after
      overwintering was followed by pathogen accumulation in asymptomatic leaves. The
      induction of necrotic leaf lesions coincided with escalation of H. fraxineus DNA
      levels and changes in proportion of biotrophs, followed by an increase of
      ubiquitous endophytes with pathogenic potential. H. fraxineus uses high propagule
      pressure to establish in leaves as quiescent thalli that switch to pathogenic
      mode once these thalli reach a certain threshold - the massive feedback from the
      saprophytic phase enables this fungus to challenge host defenses and the resident
      competitors in mid-season when their density in host tissues is still low.
      Despite the general correspondence between the ITS-1 and ITS-2 datasets, marker
      biases were observed, which suggests that multiple barcodes provide better
      overall representation of mycobiomes.

PMID- 27716952
TI  - New Oral Anticoagulants in Nonvalvular Atrial Fibrillation.
AB  - The choice of an oral anticoagulant (OAC) for patients with nonvalvular atrial
      fibrillation (NVAF) is a major and complex clinical decision taking into account
      the individual risk-benefit ratio and bearing in mind the chronicity of therapy.
      This review focuses on the safety and efficacy of new oral anticoagulants (NOACs)
      compared with conventional vitamin K antagonists (VKA) in patients with NVAF.
      Current data suggest that NOACs are at least as effective and safe as VKAs for
      most NVAF subjects. The NOACs do not mandate dietary restrictions and regular
      pharmacodynamic monitoring, and they seem to have lesser incidence of
      intracranial or fatal bleeding when compared with VKAs. However, both dabigatran
      150 twice daily and rivaroxaban have a slightly higher incidence of
      gastrointestinal bleeding when compared with VKAs. The article will delineate the
      current knowledge as well as scientific gaps related to the choice and dosage of
      anticoagulation regimens for various NVAF subsets and will address certain common
      clinical scenarios requiring special considerations. The article also addresses
      the shortcomings of NOACs: lack of therapeutic pharmacokinetic and
      pharmacodynamic targets, absence of tools to assess compliance and efficacy,
      rigid and limited dosage options, and absence of effective and inexpensive
      reversal agents.

PMID- 27716953
TI  - Validation of a serum neutralization test for detection of antibodies specific to
      cyprinid herpesvirus 3 in infected common and koi carp (Cyprinus carpio).
AB  - Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of a serious infective,
      notifiable disease affecting common carp and varieties. In survivors, infection
      is generally characterized by a subclinical latency phase with restricted viral
      replication. The CyHV-3 genome is difficult to detect in such carrier fish that
      represent a potential source of dissemination if viral reactivation occurs. In
      this study, the analytical and diagnostic performance of an alternative serum
      neutralization (SN) method based on the detection of CyHV-3-specific antibodies
      was assessed using 151 serum or plasma samples from healthy and naturally or
      experimentally CyHV-3-infected carp. French CyHV-3 isolate 07/108b was
      neutralized efficiently by sera from carp infected with European, American and
      Taiwanese CyHV-3 isolates, but no neutralization was observed using sera specific
      to other aquatic herpesviruses. Diagnostic sensitivity, diagnostic specificity
      and repeatability of 95.9%, 99.0% and 99.3%, respectively, were obtained, as well
      as a compliance rate of 89.9% in reproducibility testing. Neutralizing antibodies
      were steadily detected in infected carp subjected to restrictive or permissive
      temperature variations over more than 25 months post-infection. The results
      suggest that this non-lethal diagnostic test could be used in the future to
      improve the epidemiological surveillance and control of CyHV-3 disease.

PMID- 27716954
TI  - Disruption of Integrated Neuronal and Astrocytic Signaling Contributes to Alcohol
      Use Disorder.

PMID- 27716955
TI  - Computation of Femoral Canine Morphometric Parameters in Three-Dimensional
      Geometrical Models.
AB  - OBJECTIVE: To define and validate a method for the measurement of 3-dimensional
      (3D) morphometric parameters in polygonal mesh models of canine femora. STUDY
      DESIGN: Ex vivo/computerized model. SAMPLE POPULATION: Sixteen femora from 8
      medium to large-breed canine cadavers (mean body weight 28.3 kg, mean age 5.3
      years). METHODS: Femora were measured with a 3D scanner, obtaining 3D meshes. A
      computer-aided design-based (CAD) software tool was purposely developed, which
      allowed automatic calculation of morphometric parameters on a mesh model.
      Anatomic and mechanical lateral proximal femoral angles (aLPFA and mLPFA),
      anatomic and mechanical lateral distal femoral angles (aLDFA and mLDFA), femoral
      neck angle (FNA), femoral torsion angle (FTA), and femoral varus angle (FVA) were
      measured in 3D space. Angles were also measured onto projected planes and
      radiographic images. RESULTS: Mean (SD) femoral angles (degrees) measured in 3D
      space were: aLPFA 115.2 (3.9), mLPFA 105.5 (4.2), aLDFA 88.6 (4.5), mLDFA 93.4
      (3.9), FNA 129.6 (4.3), FTA 45 (4.5), and FVA -1.4 (4.5). Onto projection planes,
      aLPFA was 103.7 (5.9), mLPFA 98.4 (5.3), aLDFA 88.3 (5.5), mLDFA 93.6 (4.2), FNA
      132.1 (3.5), FTA 19.1 (5.7), and FVA -1.7 (5.5). With radiographic imaging, aLPFA
      was 109.6 (5.9), mLPFA 105.3 (5.2), aLDFA 92.6 (3.8), mLDFA 96.9 (2.9), FNA 120.2
      (8.0), FTA 30.2 (5.7), and FVA 2.6 (3.8). CONCLUSION: The proposed method gives
      reliable and consistent information about 3D bone conformation. Results are
      obtained automatically and depend only on femur morphology, avoiding any operator
      related bias. Angles in 3D space are different from those measured with standard
      radiographic methods, mainly due to the different definition of femoral axes.

PMID- 27716956
TI  - FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients
      with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence.
AB  - BACKGROUND: A common single nucleotide polymorphism (C385A) in the human fatty
      acid amide hydrolase (FAAH) gene has been associated with decreased distress
      responses in healthy volunteers, but its role in psychiatric disorders remains
      unknown. Here, we obtained genotypes and carried out a secondary analysis of
      subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and
      alcohol dependence (AD). We evaluated the effects of C385A variation on
      behavioral and biochemical biomarkers of distress responses. METHODS: Forty-nine
      patients with PTSD and AD were admitted for 4 weeks to an experimental medicine
      unit at the National Institutes of Health Clinical Center. Following
      detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels
      were assessed in response to a challenge session using personalized auditory
      guided imagery. Over the course of the study, subjects were also evaluated for
      changes in PTSD symptom severity. RESULTS: FAAH C385A allele carriers showed a
      marked increase in serum anandamide levels at baseline and throughout the stress
      challenge procedure compared with C allele homozygotes, while levels of eCBs
      primarily metabolized through other enzymatic activity, such as 2
      arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers
      also had decreased subjective anxiety responses to the stress challenge. Similar
      effects of FAAH C385A genotype were found at the level of clinical PTSD symptom
      severity, in particular in the arousal domain. CONCLUSIONS: This is to our
      knowledge the first study showing that FAAH C385A variation modulates stress
      responses in subjects with disorders characterized by increased stress
      reactivity. These findings point to the eCB pathway as a promising target for
      future antistress therapeutics.

PMID- 27716958
TI  - Reproducibility of Experiments with Laboratory Animals: What Should We Do Now?

PMID- 27716957
TI  - Alcohol Withdrawal Increases Protein Kinase A Activity in the Rat Inferior
      Colliculus.
AB  - BACKGROUND: Cyclic AMP-dependent protein kinase A (PKA) signaling is a key target
      for the action of alcohol and may therefore play a role in the pathophysiology of
      alcohol withdrawal seizures (AWSs). Here, we investigated the role of PKA
      activity with respect to increased seizure susceptibility in rats that were
      subjected to alcohol withdrawal. METHODS: Adult male Sprague Dawley rats received
      3 daily doses of ethanol (EtOH) (or vehicle) for 4 consecutive days. Rats were
      then tested for susceptibility to acoustically evoked AWSs 3, 24, and 48 hours
      after the last alcohol dose. In separate experiments, the inferior colliculus
      (IC) was collected at these same time points from rats subjected to alcohol
      withdrawal and control rats following alcohol withdrawal. PKA activity, catalytic
      Calpha (PKACalpha ) protein, regulatory RIIalpha (PKARIIalpha ) protein, and
      RIIbeta (PKARIIbeta ) protein were measured in the IC. Lastly, in situ
      pharmacological studies were performed to evaluate whether inhibiting PKA
      activity in the IC suppressed AWSs. RESULTS: In the EtOH-treated group, AWSs were
      observed at the 24-hour time point, but not at the 3-hour or 48-hour time points.
      In the IC, PKA activity was significantly higher both 3 hours (i.e., before AWS
      susceptibility) and 24 hours after the last alcohol dose (when AWS susceptibility
      peaked) than in control rats. Consistent with these findings, protein levels of
      the PKACalpha subunit were significantly increased in the IC both 3 and 24 hours
      after the last alcohol dose. Lastly, in situ inhibition of PKA activity within
      the IC suppressed AWSs. CONCLUSIONS: The increase in PKA activity and PKACalpha
      protein expression in the IC preceded the occurrence of AWSs, and inhibiting PKA
      activity within the IC suppressed acoustically evoked AWSs. Together, these
      findings suggest that altered PKA activity plays a key role in the pathogenesis
      of AWSs.

PMID- 27716959
TI  - First record of Tetramicra brevifilum in lumpfish (Cyclopterus lumpus, L.).
AB  - A microsporidian species with 98.3-98.4% nucleotide identity to Tetramicra
      brevifilum (Journal of Fish Diseases, 3, 1980, 495) was diagnosed in lumpfish
      (Cyclopterus lumpus, L.) broodstock held at a breeding and rearing facility in
      western Ireland. The fish were wild-caught from the west coast of Ireland, and
      the first case was diagnosed one year after capture. Clinical signs included
      severe bloating, lethargy, exophthalmos, anorexia, white patches on the cornea
      and externally visible parasitic cysts on skin and fins. Necropsy revealed severe
      ascites, white nodules and vacuoles in all the internal organs and partial
      liquefaction of the skeletal muscle. On histological examination, microsporidian
      xenomas were observed in all internal organs, the skin, skeletal muscle, gills
      and the eyes. The microsporidian species was identified by molecular analysis and
      transmission electron microscopy. This is the first record of T. brevifilum
      infecting lumpfish, and the disease is considered to be of potential significance
      to the rising aquaculture industry of this species.

PMID- 27716960
TI  - The Formation, Elimination, Interpretation, and Future Research Needs of
      Phosphatidylethanol for Research Studies and Clinical Practice.

PMID- 27716961
TI  - Left ventricular stiffness estimated by diastolic wall strain is associated with
      paroxysmal atrial fibrillation in structurally normal hearts.
AB  - BACKGROUND: Left ventricular (LV) diastolic dysfunction depends on an impaired
      relaxation and stiffness. Abnormal LV relaxation contributes to the development
      of atrial fibrillation (AF), but the role of LV stiffness in AF remains unclear.
      HYPOTHESIS: Diastolic wall strain (DWS), a load-independent, noninvasive direct
      measure of LV stiffness, correlates with prevalent AF. METHODS: This study
      included 328 consecutive subjects with structurally normal hearts: 164 paroxysmal
      AF patients and 164 age- and sex-matched (1:1) controls. We calculated the DWS
      from the M-mode echocardiographic measurements of the LV posterior wall thickness
      at end-systole and end-diastole during sinus rhythm. RESULTS: The DWS was lower
      in the AF patients (0.35 +/- 0.07) than in the controls (0.41 +/- 0.06; P <
      0.001). After adjusting for the risk factors of AF using a conditional logistic
      regression analysis, a history of hypertension, plasma brain-type natriuretic
      peptide level, and DWS were independently associated with AF prevalence, whereas
      body mass index, LV mass index, left atrial volume, and any conventional indices
      of the diastolic function were not. A low DWS (<0.380) was the strongest
      indicator of AF (odds ratio: 6.22, 95% confidence interval: 3.08-14.2, P <
      0.001). CONCLUSIONS: Increased LV stiffness estimated by DWS was a strong
      determinant of the prevalence of AF. LV stiffness may play a role in the
      pathogenesis of paroxysmal AF in structurally normal hearts.

PMID- 27716962
TI  - Acetaldehyde Disrupts Interferon Alpha Signaling in Hepatitis C Virus-Infected
      Liver Cells by Up-Regulating USP18.
AB  - BACKGROUND: Alcohol consumption exacerbates the pathogenesis of hepatitis C virus
      (HCV) infection and worsens disease outcomes. The exact reasons are not clear
      yet, but they might be partially attributed to the ability of alcohol to further
      suppress the innate immunity. Innate immunity is known to be already decreased by
      HCV in liver cells. METHODS: In this study, we aimed to explore the mechanisms of
      how alcohol metabolism dysregulates IFNalpha signaling (STAT1 phosphorylation) in
      HCV+ hepatoma cells. To this end, CYP2E1+ Huh7.5 cells were infected with HCV and
      exposed to the acetaldehyde (Ach) generating system (AGS). RESULTS: Continuously
      produced Ach suppressed IFNalpha-induced STAT1 phosphorylation, but increased the
      level of a protease, USP18 (both measured by Western blot), which interferes with
      IFNalpha signaling. Induction of USP18 by Ach was confirmed in primary human
      hepatocyte cultures and in livers of ethanol-fed HCV transgenic mice. Silencing
      of USP18 by specific siRNA attenuated the pSTAT1 suppression by Ach. The
      mechanism by which Ach down-regulates pSTAT1 is related to an enhanced
      interaction between IFNalphaR2 and USP18 that finally dysregulates the cross talk
      between the IFN receptor on the cell surface and STAT1. Furthermore, Ach
      decreases ISGylation of STAT1 (protein conjugation of a small ubiquitin-like
      modifier, ISG15, Western blot), which preserves STAT1 activation. Suppressed
      ISGylation leads to an increase in STAT1 K48 polyubiquitination which allows
      pSTAT1 degrading by proteasome. CONCLUSIONS: We conclude that Ach disrupts
      IFNalpha-induced STAT1 phosphorylation by the up-regulation of USP18 to block the
      innate immunity protection in HCV-infected liver cells, thereby contributing to
      HCV-alcohol pathogenesis. This, in part, may explain the mechanism of HCV
      infection exacerbation/progression in alcohol-abusing patients.

PMID- 27716963
TI  - Mechanisms Involved in Disruption of Adipose Tissue Mass Resulting from Chronic
      Unhealthy Alcohol Consumption.

PMID- 27716964
TI  - Immediate Neural Plasticity Involving Reaction Time in a Saccadic Eye Movement
      Task is Intact in Children With Fetal Alcohol Spectrum Disorder.
AB  - BACKGROUND: Saccades are rapid eye movements that bring an image of interest onto
      the retina. Previous research has found that in healthy individuals performing
      eye movement tasks, the location of a previous visual target can influence
      performance of the saccade on the next trial. This rapid behavioral adaptation
      represents a form of immediate neural plasticity within the saccadic circuitry.
      Our studies have shown that children with fetal alcohol spectrum disorder (FASD)
      are impaired on multiple saccade measures. We therefore investigated these
      previous trial effects in typically developing children and children with FASD to
      measure sensory neural plasticity and how these effects vary with age and
      pathology. METHODS: Both typically developing control children (n = 102; mean age
      = 10.54 +/- 3.25; 48 males) and children with FASD (n = 66; mean age = 11.85 +/-
      3.42; 35 males) were recruited from 5 sites across Canada. Each child performed a
      visually guided saccade task. Reaction time and saccade amplitude were analyzed
      and then assessed based on the previous trial. RESULTS: There was a robust
      previous trial effect for both reaction time and amplitude, with both the control
      and FASD groups displaying faster reaction times and smaller saccades during
      alternation trials (visual target presented on the opposite side to the previous
      trial). Children with FASD exhibited smaller overall mean amplitude and smaller
      amplitude selectively on alternation trials compared with controls. The effect of
      the previous trial on reaction time and amplitude did not differ across childhood
      and adolescent development. CONCLUSIONS: Children with FASD did not display any
      significant reaction time differences, despite exhibiting numerous deficits in
      motor and higher level cognitive control over saccades in other studies. These
      results suggest that this form of immediate neural plasticity in response to
      sensory information before saccade initiation remains intact in children with
      FASD. In contrast, the previous trial effect on amplitude suggests that the motor
      component of saccades may be affected, signifying differential vulnerability to
      prenatal alcohol exposure.

PMID- 27716965
TI  - Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia
      but not ongoing pain in a rat model of bone cancer pain.
AB  - Bone cancer pain (BCP) is the most common complication in patients with bone
      cancer. Glial cell line-derived neurotrophic factor (GDNF) is believed to be
      involved in chronic pain conditions. In this article, the expression and roles of
      GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256
      rat mammary gland carcinoma cells. Significant mechanical and thermal
      hyperalgesia and ongoing pain were observed beginning as early as day 5 post
      injection. The expression level of GDNF protein examined on day 16 after tibia
      injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal
      cord, but not in other spinal levels or the anterior cingulate cortex.
      Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased.
      Furthermore, normalizing GDNF expression with lentiviral vector constructs in the
      spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal
      glial activation, and pERK induction induced by tibia injection, but did not
      affect ongoing pain. Together these findings provide new evidence for the use of
      GDNF as a therapeutic treatment for bone cancer pain states.

PMID- 27716966
TI  - The electrophysiological signature of deliberate rule violations.
AB  - Humans follow rules by default, and violating even simple rules induces cognitive
      conflict for the rule breaker. Previous studies revealed this conflict in various
      behavioral measures, including response times and movement trajectories. Based on
      these experiments, we investigated the electrophysiological signature of
      deliberately violating a simple stimulus-response mapping rule. Such rule
      violations were characterized by a delayed and attenuated P300 component when
      evaluating a rule-relevant stimulus, most likely reflecting increased response
      complexity. This parietal attenuation was followed by a frontal positivity for
      rule violations relative to correct response trials. Together, these results
      reinforce previous findings on the need to inhibit automatic S-R translation when
      committing a rule violation, and they point toward additional factors involved in
      rule violation. Candidate processes such as negative emotional responses and
      increased monitoring should be targeted by future investigations.

PMID- 27716967
TI  - Estimation of dielectric values for tissue water in the Terahertz range.
AB  - As the availability of Terahertz (THz) sources and their application expands,
      interaction with biological material needs to be well-understood. In order to
      accurately estimate the energy absorption pattern in skin and other tissues in
      the THz and far Infrared regions, values of dielectric parameters epsilon and
      sigma are required. We present an approach for tissue water, which uses
      literature values of complex refractive index for pure water together with some
      considerations regarding the effects of dissolved salts. The approach also
      involves modeling of Debye and Lorentz absorption parameters, which provides a
      method for the estimation of epsilon and sigma in other tissues.
      Bioelectromagnetics. 37:563-567, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27716968
TI  - Special considerations for therapeutic choice of non-vitamin K antagonist oral
      anticoagulants for Japanese patients with nonvalvular atrial fibrillation.
AB  - Nonvalvular atrial fibrillation (AF) is a risk factor for stroke in elderly
      patients. Although warfarin has been used to prevent AF-associated stroke for
      more than 50 years, non-vitamin K antagonist oral anticoagulants (NOACs)
      including dabigatran, rivaroxaban, apixaban, and edoxaban recently have been
      developed to overcome the disadvantages of warfarin. Based on the results of NOAC
      clinical trials, Savelieva and Camm made recommendations regarding selection of
      NOACs in patients with nonvalvular AF. Recent accumulating evidence indicates
      that NOACs work differently in Asian and non-Asian individuals. In this review,
      we discuss the results of the large, randomized, phase 3 international clinical
      trials on NOACs, the subanalyses of Asians, and a Japanese phase 3 clinical trial
      of rivaroxaban to discriminate Japanese patient-specific characteristics with
      regard to their responses to NOACs and make recommendations. Our analysis
      revealed that rivaroxaban decreased the incidence of gastrointestinal (GI)
      bleeding compared with warfarin in Japanese patients. The efficacy results showed
      that rivaroxaban significantly decreased the incidence of ischemic stroke (hazard
      ratio: 0.40, 95% confidence interval: 0.17-0.96) compared with warfarin. The
      lower incidence of GI bleeding and ischemic stroke may be specific to Japanese
      patients. Based on the present and previous results, the following
      recommendations regarding the selection of NOACs are added in the Camm chart for
      Japanese patients: edoxaban for patients with a high risk of bleeding and those
      with a previous stroke; and rivaroxaban for patients with a high risk of ischemic
      stroke and a low bleeding risk, and those with previous GI bleeding.

PMID- 27716969
TI  - Contribution of biomechanical forces to inflammation-induced bone resorption.
AB  - AIM: This study aimed to evaluate the contribution of biomechanical loading to
      inflammation-induced tissue destruction. MATERIALS AND METHODS: A total of 144
      adult Holtzman rats were randomly assigned into four experimental groups: control
      (C), ligature-induced periodontal disease (P), orthodontic movement (OM), and
      combination group (OMP). On days 1, 3, 7, and 15, following baseline, nine
      animals from each experimental group were killed. Bone volume fraction (BVF) and
      bone mineral density (BMD) were measured using micro-computed tomography.
      Expression and synthesis profile of cytokines and receptors of inflammation in
      gingival tissues were evaluated by PCR array assay and multiplex immunoassay.
      RESULTS: At 15 days, the OMP group presented a significantly (p < 0.05) lower BVF
      and BMD levels when compared to all the other groups. The OMP group presented the
      highest number of upregulated protein targets in comparison to the other groups.
      Furthermore, the gene expression and protein levels of CCL2, CCL3, IL-1beta, IL1
      alpha, IL-18, TNF-alpha, and VEGF were significantly (p < 0.05) higher in the OMP
      group when compared to the P group. CONCLUSIONS: In summary, mechanical loading
      modulates the inflammatory response of periodontal tissues to periodontal disease
      by increasing the expression of several pro-inflammatory mediators and receptors,
      which leads to increased bone resorption.

PMID- 27716971
TI  - REPORT OF THE 48TH ANNUAL MEETING OF CHEIRON: THE INTERNATIONAL SOCIETY FOR THE
      HISTORY OF THE BEHAVIORAL AND SOCIAL SCIENCES MEETING JOINTLY WITH EUROPEAN
      SOCIETY FOR THE HISTORY OF HUMAN SCIENCES (ESHHS): www.uakron.edu/cheiron/ (where
      the full program and abstracts are posted).

PMID- 27716970
TI  - Soft tissue volume augmentation at dental implant sites using a volume stable
      three-dimensional collagen matrix - histological outcomes of a preclinical study.
AB  - AIM: The aim of this study was to test whether or not soft tissue augmentation
      with a collagen matrix (VCMX) leads to a similar increase in ridge width around
      dental implants compared to the use of an autogenous subepithelial connective
      tissue graft (SCTG). MATERIALS AND METHODS: In 12 dogs, immediate dental implants
      were placed with simultaneous guided bone regeneration. Three months later, soft
      tissue volume augmentation was performed by randomly allocating three treatment
      modalities to these sites [VCMX, SCTG, sham-operated group (control)]. Dogs were
      sacrificed at 1 (n = 4), 2 (n = 4) or 6 months (n = 4). Descriptive histology and
      histomorphometric measurements for soft tissue thickness were performed on non
      decalcified sections. RESULTS: The horizontal soft tissue thickness was maximal
      at the most coronal level (alveolar crest) at 1 month (VCMX: 2.1 +/- 1.6 mm;
      SCTG: 2.5 +/- 1.7 mm; p = 0.877) and decreased until 6 months. At 6 months, the
      greatest mucosal thickness was at a level 3.5 mm below the crest (VCMX: 0.8 +/-
      0.3 mm; SCTG: 0.7 +/- 0.2 mm) (p = 0.754). Control sites revealed no relevant
      soft tissue augmentation at any level and any time-point. Tissue integration for
      VCMX and SCTG were favourable with minimal inflammatory reactions. CONCLUSIONS:
      Soft tissue volume augmentation at implant sites was obtained to a similar extent
      using VCMX and SCTG up to 2 months. Thereafter, degradation and remodelling
      processes were enhanced leading to a minimal increase in soft tissue thickness at
      6 months for VCMX and SCTG.

PMID- 27716972
TI  - CITATION: 2016 CHEIRON BOOK PRIZE.

PMID- 27716973
TI  - NEWS AND NOTES-FALL 2016.

PMID- 27716974
TI  - FORUM FOR THE HISTORY OF HUMAN SCIENCES: REPORTS FOR JHBS AUGUST 2016.

PMID- 27716975
TI  - When more is better: how data sharing would accelerate genomic selection of crop
      plants.
AB  - Genomic selection is proving an effective new strategy for increasing breeding
      efficiency in a wide variety of cereal species - the staple crops that feed the
      world. A preponderance of studies, reviewed here, has confirmed that the more
      correlated phenotypic and environmental data that are used to feed genomics
      assisted breeding models, the better the prediction accuracies of the models and
      the more useful the breeding outcomes. We argue that based on these empirical
      results, new alliances to share data across genomic selection breeding programs
      are critical to the rapid development and deployment of new crop varieties.

PMID- 27716976
TI  - Exploration of Core Symptoms for the Diagnosis of Alcohol Dependence in the ICD
      10.
AB  - BACKGROUND: The classification of alcohol use disorder has changed over the past
      century. Now, the conceptualization of alcohol dependence is still controversial.
      Accumulating evidence has shown the reliability and validity for the diagnosis of
      alcohol dependence in the ICD-10 and DSM-IV. However, the meaning and association
      of the respective diagnostic items, which are descriptive of representative
      symptoms, have hardly been examined. The core symptom of substance use disorder
      has been debated in various situations, but has never been elucidated logically.
      METHODS: We consecutively registered 192 patients with alcohol-related problems
      who visited our hospital for the first time during a certain period. The
      relations and principal components among the checked items of the ICD-10
      diagnostic criteria were examined statistically. RESULTS: Three diagnostic items
      in the ICD-10 were strongly correlated with each other and were thought to form
      the core symptoms of alcohol dependence: "strong desire," "difficulties in
      controlling," and "neglect of pleasures." One major physical phenomenon,
      "withdrawal," seemed to complement the core symptoms in the diagnosis of alcohol
      dependence. Another physical phenomenon, "tolerance," was demonstrated to be a
      relatively independent item. The principal component analysis also demonstrated
      that the diagnostic item "difficulties in controlling" had the maximum component
      loading value, followed by 2 items, "neglect of pleasures" and "strong desire."
      CONCLUSIONS: The core symptomatic elements in the diagnosis of alcohol dependence
      were statistically suggested in this study. Knowledge of the relations and
      components among the diagnostic items of alcohol dependence might also be
      applicable to other forms of substance use dependence and behavioral addiction.

PMID- 27716977
TI  - The Need for a Lengthier Cryolesion Can Predict a Worse Outcome in 3D
      Cryoablation of AV Nodal Slow Pathway in Children.
AB  - BACKGROUND: Transcatheter cryoablation is a well-established technique for the
      treatment of atrioventricular nodal reentry tachycardia (AVNRT) in children.
      Nevertheless, atrioventricular nodal slow-pathway conduction may recur after an
      acutely successful procedure. The aim of this study was to evaluate the long-term
      outcome of acutely successful AVNRT cryoablations in pediatric patients in case
      of focal cryolesion and in case of need for High-Density Linear Lesion (HDLL)
      cryoablation due to focal failure. METHODS: Sixty-nine consecutive pediatric
      patients (30 males, mean age 12.4 +/- 3.2 years; range: 5.4-18.0 years) underwent
      3D-guided cryoablation for AVNRT at our institution from July 2013 to November
      2014. When a focal cryoablation was acutely unsuccessful, a 3D-guided HDLL was
      created delivering multiple overlapping cryolesions/cryoenergy applications from
      the ventricular side of the tricuspid annulus to the atrial side, including the
      site of focal cryoablation if transiently successful. RESULTS: No permanent
      cryoablation-related complications occurred. Acute success rate was 98.5% (68 out
      of 69): in 55.9% (38 out of 68) with focal-lesion and in 44.1% (30 out of 68)
      with HDLL. Mean follow-up was 25.3 months and AVNRT recurrence rate was 13.2%
      (nine out of 68): 5.2% (two out of 38) with focal lesion and 23.3% (seven out of
      30) with HDLL (P = 0.036). CONCLUSIONS: In cryoablation of AVNRT in children, the
      need for a more aggressive protocol (HDLL), due to the failure of focal ablation,
      is strictly related to higher recurrence rates. Indeed, AVNRT recurrences after
      cryoablation in children seem to be due to a larger and deeper substrate rather
      than due to the type of energy used.

PMID- 27716978
TI  - Influence of Successful Chronic Hepatitis C Virus Treatment with
      Ledipasvir/Sofosbuvir on Warfarin Dosing Requirements in Four Veterans.
AB  - STUDY OBJECTIVE: To describe international normalized ratio (INR) trends and
      warfarin dosage adjustments required for four veterans who were receiving
      warfarin therapy and started treatment for hepatitis C virus (HCV) with
      ledipasvir/sofosbuvir with or without ribavirin. DESIGN: Case series. SETTING:
      Pharmacist-led anticoagulation clinic in a Veterans Affairs Health Care System.
      PATIENTS: Four patients aged 59-66 years who were receiving warfarin and had
      stable, therapeutic INRs and started ledipasvir/sofosbuvir therapy with or
      without ribavirin for HCV infection. MEASUREMENTS AND MAIN RESULTS: All four
      patients developed subtherapeutic INRs after the addition of
      ledipasvir/sofosbuvir with or without ribavirin. An increase in weekly warfarin
      dose ranging from 14-67% was required, with changes in warfarin doses starting 2
      3 weeks after ledipasvir/sofosbuvir initiation. Two patients required dose
      reductions after HCV treatment completion, whereas the other two did not. Use of
      the Drug Interaction Probability Scale indicated that the interaction between
      warfarin and ledipasvir/sofosbuvir was doubtful (score of 1 [two patients]) or
      possible (score of 4 [two patients]). The mechanism of this interaction is
      unknown but may be related to improvements in hepatic function during HCV
      treatment. CONCLUSION: To our knowledge, this is the first case series describing
      a possible drug interaction between warfarin and ledipasvir/sofosbuvir (with or
      without ribavirin). Close monitoring is warranted when ledipasvir/sofosbuvir is
      initiated in patients receiving anticoagulation therapy with warfarin, especially
      those with evidence of cirrhosis prior to treatment. This is particularly
      important in the first month after starting treatment and the first month after
      completion. Failure to monitor and achieve therapeutic INR after HCV therapy
      completion may have the potential to result in adverse outcomes.

PMID- 27716979
TI  - Root coverage with connective tissue graft associated with coronally advanced
      flap or tunnel technique: a randomized, double-blind, mono-centre clinical trial.
AB  - AIM: The aim of this randomized clinical trial was to compare the coronally
      advanced flap (CAF) with the modified microsurgical tunnel technique (MMTT) for
      treatment of Miller class I and II recessions. MATERIAL AND METHODS: Forty
      patients with 71 gingival recessions were recruited and randomly assigned to
      either CAF or to MMTT. In both groups, a connective tissue graft was applied.
      Clinical evaluations were performed after 3, 6, and 12 months. Impressions were
      taken and digitally scanned three-dimensionally to evaluate the quantitative soft
      tissue changes in the operative region. Patient satisfaction was measured with
      the root coverage aesthetic score (RES). RESULTS: After a period of 12 months,
      significant differences were not found between the two groups. Root coverage was
      98.3% for CAF and 97.2% for MMTT. The evaluation of the aesthetic outcome using
      RES showed good results in both groups. The RES score was in accordance with
      subjective patient satisfaction. There was no significant difference in the
      amount of volumetric changes. CONCLUSIONS: CAF and MMTT with the additional use
      of a graft are equally successful in covering gingival recessions of Miller class
      I and II, with high aesthetic results. All patients indicated their willingness
      for further periodontal surgery.

PMID- 27716980
TI  - Generating human serotonergic neurons in vitro: Methodological advances.
AB  - Technologies for deriving human neurons in vitro have transformed our ability to
      study cellular and molecular components of human neurotransmission. Three groups,
      including our own, have recently published methods for efficiently generating
      human serotonergic neurons in vitro. Remarkably, serotonergic neurons derived
      from each method robustly produce serotonin, express raphe genes, are
      electrically active, and respond to selective serotonin reuptake inhibitors in
      vitro. Two of the methods utilize transdifferentiation technology by
      overexpressing key serotonergic transcription factors. The third and most recent
      method involves differentiating induced pluripotent stem cells (iPSCs) to
      serotonergic neurons using developmental patterning cues. In this mini-review, we
      briefly describe the developmental programs governing serotonergic specification
      in vivo and how they have been harnessed to achieve serotonergic differentiation
      in vitro. We discuss the distinct and overlapping features of the recently
      published methodologies and their value in the context of in vitro disease
      modeling. Also see the video abstract here.

PMID- 27716981
TI  - Carnosic acid as a component of rosemary extract stimulates skeletal muscle cell
      glucose uptake via AMPK activation.
AB  - Compounds that increase the activity of the energy sensor AMP-activated kinase
      (AMPK) have the potential to regulate blood glucose levels. Although rosemary
      extract (RE) has been reported to activate AMPK and reduce blood glucose levels
      in vivo, the chemical components responsible for these effects are not known. In
      the present study, we measured the levels of the polyphenol carnosic acid (CA) in
      RE and examined the effects and the mechanism of action of CA on glucose
      transport system in muscle cells. High performance liquid chromatography (HPLC)
      was used to measure the levels of CA in RE. Parental and GLUT4myc or GLUT1myc
      overexpressing L6 rat myotubes were used. Glucose uptake was assessed using [3 H]
      2-deoxy-d-glucose. Total and phosphorylated levels of Akt and AMPK were measured
      by immunoblotting. Plasma membrane GLUT4myc and GLUT1myc levels were examined
      using a GLUT translocation assay. Statistics included analysis of variance
      (ANOVA) followed by Tukey's post-hoc test. At concentrations found in rosemary
      extract, CA stimulated glucose uptake in L6 myotubes. At 2.0 MUmol/L CA a
      response (226 +/- 9.62% of control, P=.001), similar to maximum insulin (201 +/-
      7.86% of control, P=.001) and metformin (213 +/- 10.74% of control, P=.001) was
      seen. Akt phosphorylation was not affected by CA while AMPK and ACC
      phosphorylation was increased and the CA-stimulated glucose uptake was
      significantly reduced by the AMPK inhibitor compound C. Plasma membrane GLUT4 or
      GLUT1 glucose transporter levels were not affected by CA. Our study shows
      increased muscle cell glucose uptake and AMPK activation by low CA
      concentrations, found in rosemary extract, indicating that CA may be responsible
      for the antihyperglycemic properties of rosemary extract seen in vivo.

PMID- 27716982
TI  - Simultaneous analysis of 35 specific antihypertensive adulterants in dietary
      supplements using LC/MS/MS.
AB  - A sensitive and specific LC/MS/MS method was developed for the simultaneous
      analysis of 35 compounds used for treating hypertension as adulterants in dietary
      supplements. The method was validated for specificity, linearity, accuracy,
      precision, limit of detection, limit of quantitation, stability and recovery. The
      limit of detection and limit of quantitation ranged from 0.20 to 20.0 and 0.50 to
      60.0 ng/g, respectively. The linearity was good (r2  > 0.999), with intra- and
      interday precision levels of 0.43-7.87% and 0.65-9.95% and the intra- and
      interday accuracies of 84.36-115.82% and 83.78-118.69%, respectively. The
      stability (relative standard deviation) was <14.75%. The mean recovery was 80.81
      117.86% (relative standard deviation <10.00%). Ninety-seven commercial dietary
      supplements available in South Korea were analyzed. While none contained
      detectable amounts of the 35 antihypertensive compounds, the developed LC/MS/MS
      procedure can be used for routine analysis to monitor illegal adulteration in
      various forms of dietary supplements.

PMID- 27716983
TI  - Pharmacokinetics of Ceftazidime-Avibactam in Two Patients With KPC-Producing
      Klebsiella pneumoniae Bacteremia and Renal Impairment.
AB  - Limited data exist regarding optimal dosing of ceftazidime/avibactam (C/A) in
      patients with unique physiology, who were excluded from published clinical
      trials. Data are also lacking regarding clinical efficacy of C/A in patients with
      infections due to multidrug-resistant gram-negative pathogens. To expand
      knowledge in these areas, we present pharmacokinetic data from two patients with
      Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream
      infections, both of whom had renal impairment, and one of whom was morbidly
      obese. C/A was initiated in both patients at higher doses than those recommended
      in the package insert. To assess adequacy of dosing at steady state, a trough was
      drawn before and consecutive levels were drawn after a C/A dose such that half
      life and volume of distribution for ceftazidime and avibactam could be calculated
      using the Sawchuk-Zaske method. Both patients cleared their bloodstream infection
      without evidence of toxicity. Patient 1 and patient 2 had prolonged half-lives
      for ceftazidime (22.8 and 14.5 hours, respectively) and avibactam (19.6 and 11.3
      hours, respectively). Both patients had volumes of distribution significantly
      larger than those listed in the package insert: ceftazidime 47.1 L and 24.7 L and
      avibactam 50.3 L and 38.7 L for patients 1 and 2, respectively. Considering the
      larger volumes of distribution and levels observed in our patients, recommended
      doses and intervals may not be sufficient for obese patients with renal failure,
      especially for those infected with KPC-producing organisms. Additional efficacy
      and pharmacokinetic data are still needed for this agent to define optimal dosing
      strategies in patients commonly encountered in clinical practice.

PMID- 27716984
TI  - Letter to the Editor re Hergt et al "Use of a 2-tier histologic grading system
      for canine cutaneous mast cell tumors on cytology specimens".

PMID- 27716985
TI  - D-tyrosine affects aggregation behavior of Pantoea agglomerans.
AB  - D-amino acids have been proved to disassemble biofilms by disassociating the
      matrix. Pantoea agglomerans is characterized by the formation of another kind of
      multicellular structure called symplasmata, which also remains the ability to
      form biofilms. In this study, a rice diazotrophic endophyte P. agglomerans YS19
      was selected as a model strain to explore the effects of D-amino acids on these
      two kinds of cell aggregate structures. It was discovered that D-tyrosine
      disassociates biofilm, yet promotes symplasmata formation. D-tyrosine showed no
      influence on bacterial growth yet promoted the bacterial motility and inhibited
      the expression of cellular MalE and OmpF proteins, which enriched our knowledge
      of the biological effect of D-amino acids and expanded the research ideas of
      symplasmata formation.

PMID- 27716986
TI  - Evaluation of performance of veterinary in-clinic hematology analyzers.
AB  - BACKGROUND: A previous study provided information regarding the quality of in
      clinic veterinary biochemistry testing. However, no similar studies for in-clinic
      veterinary hematology testing have been conducted. OBJECTIVE: The objective of
      this study was to assess the quality of hematology testing in veterinary in
      clinic laboratories using results obtained from testing 3 levels of canine EDTA
      blood samples. METHODS: Clinicians prepared blood samples to achieve measurand
      concentrations within, below, and above their RIs and evaluated the samples in
      triplicate using their in-clinic analyzers. Quality was assessed by comparison of
      calculated total error with quality requirements, determination of sigma metrics,
      use of a quality goal index, and agreement between in-clinic and reference
      laboratory instruments. Suitability for statistical quality control was
      determined using adaptations from the computerized program, EZRules3. RESULTS:
      Evaluation of 10 veterinary in-clinic hematology analyzers showed that these
      instruments often fail to meet quality requirements. At least 60% of analyzers
      reasonably determined RBC, WBC, HCT, and HGB, when assessed by most quality goal
      criteria; platelets were less reliably measured, with 80% deemed suitable for low
      platelet counts, but only 30% for high platelet counts, and automated
      differential leukocyte counts were generally considered unsuitable for clinical
      use with fewer than 40% of analyzers meeting the least stringent quality goal
      requirements. Fewer than 50% of analyzers were able to meet requirements for
      statistical quality control for any measurand. CONCLUSION: These findings reflect
      the current status of in-clinic hematology analyzer performance and provide a
      basis for future evaluations of the quality of veterinary laboratory testing.

PMID- 27716987
TI  - Efficacy of imidazolquinoline on treatment of condyloma acuminatum of the buccal
      mucosa.
AB  - The condylomata acuminata is a benign epithelial neoplasm induced by
      papillomavirus, and it is characterized by the proliferation of stratified
      squamous epithelial tissue that affects the anogenital and oral mucosa. It is
      considered to be a sexually transmitted disease and has a higher prevalence in
      individuals infected with human immunodeficiency virus. Various therapies have
      been used for the removal of lesions, such as cryotherapy, surgical laser and
      surgical excision, which are painful and scarring. These techniques, however, do
      not eliminate the virus and relapses are common shortly after treatment. The use
      of immunomodulators has been proposed to be an alternative treatment, as
      imidazolquinoline has been shown to be effective in the treatment of lesions in
      the anogenital region. However, its use in the oral cavity has been the subject
      of few reports in the literature. Thus, the objective of this study is to
      describe a case of warts in the labial mucosa of an HIV positive patient using
      imidazolquinoline 5%.

PMID- 27716990
TI  - Evaluation of the American college of surgeons thyroid and parathyroid ultrasound
      course: Results of a web-based survey.
AB  - OBJECTIVES/HYPOTHESIS: The American College of Surgeons Thyroid and Parathyroid
      Ultrasound Skills-Oriented Course (TPUSC) was designed to teach surgeons how to
      interpret and perform office-based head and neck ultrasound (HNUS). The objective
      of this study was to survey attendees of the TPUSC to evaluate the usefulness of
      the course, to track surgeon performed HNUS practice patterns, and to help
      identify potential roadblocks to incorporation of HNUS into a surgeon's practice.
      STUDY DESIGN: Cross-sectional survey. METHODS: A Web-based survey was sent to 952
      surgeons who completed the TPUSC between 2010 and 2014. Questions included
      surgeon specialty, practice type, Likert scale rating of the TPUSC, competency
      with different HNUS procedures, and current HNUS practice patterns. RESULTS: The
      response rate was 24%. On a scale from 1 (not useful) to 5 (extremely valuable),
      the mean course usefulness rating was 4.2. Educational goals were met for 194
      (92%) surgeons, and 162 (77%) surgeons reported performing HNUS in their
      practice. Of 48 surgeons not performing HNUS, 24 (50%) attributed insufficient
      time in their clinic schedule, and 21 (44%) attributed high equipment costs.
      CONCLUSIONS: The TPUSC is a valuable educational experience for surgeons seeking
      to gain proficiency in HNUS. The majority of TPUSC graduates gain competency with
      at least one type of HNUS procedure following the course. LEVEL OF EVIDENCE: NA
      Laryngoscope, 127:1950-1958, 2017.

PMID- 27716989
TI  - Doctors Have no Right to Refuse Medical Assistance in Dying, Abortion or
      Contraception.
AB  - In an article in this journal, Christopher Cowley argues that we have
      'misunderstood the special nature of medicine, and have misunderstood the
      motivations of the conscientious objectors'. We have not. It is Cowley who has
      misunderstood the role of personal values in the profession of medicine. We argue
      that there should be better protections for patients from doctors' personal
      values and there should be more severe restrictions on the right to conscientious
      objection, particularly in relation to assisted dying. We argue that eligible
      patients could be guaranteed access to medical services that are subject to
      conscientious objections by: (1) removing a right to conscientious objection; (2)
      selecting candidates into relevant medical specialities or general practice who
      do not have objections; (3) demonopolizing the provision of these services away
      from the medical profession.

PMID- 27716991
TI  - Early-Onset 5-Fluorouracil Toxicity in a Patient Negative for Dihydropyrimidine
      Dehydrogenase Mutations: The Clinical Course of Reversal with Uridine Triacetate.
AB  - An antimetabolite pyridine analog, 5-fluorouracil (5-FU), is used to treat solid
      tumors. Early toxicities may occur at standard doses of 5-FU due to
      dihydropyrimidine dehydrogenase (DPD) deficiency. Uridine triacetate, approved by
      the Food and Drug Administration in 2015, is an oral prodrug of uridine, a
      pharmacologic antidote for 5-FU toxicity. To our knowledge, this is the first
      case report that documents the clinical course of a patient treated with uridine
      triacetate to reverse early-onset 5-FU toxicity negative for DPD mutations. We
      describe the case of a 73-year-old man with anal cancer treated with standard-of
      care chemotherapy and radiation. Two days after completion of his initial 5-FU
      infusion, the patient developed severe mucositis and extreme fatigue, followed by
      a rapid decline in his blood cell counts and fevers. The patient was initiated on
      uridine triacetate 86 hours after completion of his 5-FU infusion. Over a 10-day
      hospital length of stay, the patient's absolute neutrophil count recovered to
      within normal limits, and his mucositis significantly improved. At follow-up
      visits, the patient denied any residual symptoms of 5-FU toxicity. We describe
      the patient's clinical course from hospital presentation to 31 days after
      initiation of uridine triacetate.

PMID- 27716988
TI  - Progression of alpha-synuclein pathology in multiple system atrophy of the
      cerebellar type.
AB  - AIMS: The aim of this study was to identify early foci of alpha-synuclein (alpha
      syn pathology) accumulation, subsequent progression and neurodegeneration in
      multiple system atrophy of the cerebellar type (MSA-C). METHODS: We analysed 70
      MUm-thick sections of 10 cases with MSA-C and 24 normal controls. RESULTS: MSA-C
      cases with the lowest burden of pathology showed alpha-syn glial cytoplasmic
      inclusions (GCIs) in the cerebellum as well as in medullary and pontine
      cerebellar projections. Cerebellar pathology was highly selective and severely
      involved subcortical white matter, whereas deep white matter and granular layer
      were only mildly affected and the molecular layer was spared. Loss of Purkinje
      cells increased with disease duration and was associated with neuronal and axonal
      abnormalities. Neocortex, basal ganglia and spinal cord became consecutively
      involved with the increasing burden of alpha-syn pathology, followed by
      hippocampus, amygdala, and, finally, the visual cortex. GCIs were associated with
      myelinated axons, and the severity of GCIs correlated with demyelination.
      CONCLUSIONS: Our findings indicate that cerebellar subcortical white matter and
      cerebellar brainstem projections are likely the earliest foci of alpha-syn
      pathology in MSA-C, followed by involvement of more widespread regions of the
      central nervous system and neurodegeneration with disease progression.

PMID- 27716992
TI  - Bone mineral density is associated with left ventricular diastolic function in
      women.
AB  - BACKGROUND: Low bone mineral density (BMD) and left ventricular (LV) diastolic
      function are associated with heart failure. However, little is known about the
      association between BMD and LV diastolic function. HYPOTHESIS: BMD is
      independently related to LV diastolic function in women. METHODS: We conducted a
      cross-sectional study of 432 women. Brachial-ankle pulse wave velocity (baPWV)
      and BMD measurements were performed. LV diastolic function and structure were
      assessed by echocardiographic examination. RESULTS: BaPWV and the percentage of
      LV diastolic dysfunction increased with progressive bone loss. Moreover, partial
      correlation analysis demonstrated that BMD at spine L2-4 and at femoral neck were
      correlated with baPWV and LV diastolic function parameters after adjusting
      covariates. Multivariate logistic regression analysis revealed that osteoporosis
      was independently associated with LV diastolic dysfunction in women. CONCLUSIONS:
      Osteoporosis is independently associated with LV diastolic dysfunction in women.
      A prospective study is needed to elucidate the effects of BMD on cardiac function
      in women.

PMID- 27716993
TI  - Bone metabolism markers: Indicators of loading dose intravenous ibandronate
      treatment for bone metastases from breast cancer.
AB  - To investigate the changes in bone metabolism markers after second-line treatment
      with loading dose intravenous (i.v.) ibandronate in patients with bone metastases
      (BM) from breast cancer, 80 patients were enrolled in this study during January
      2010 to April 2014. All the patients were treated with a second-line loading dose
      ibandronate for advanced breast cancer with BM and moderate-to-severe bone pain.
      Ibandronate (6 mg) was intravenously administered on three consecutive days
      followed by maintenance treatment every 3-4 weeks. Clinical data, including pain
      score, Karnofsky performance status (KPS) score, and changes in bone metabolism
      markers, were analyzed. Sixty-two patients were included in the final analysis.
      Compared with their pre-treatment scores, patients exhibited significantly
      increased KPS scores (P < .01) and a reduced dose of analgesic medication
      (oxycodone) (P < .01) after 3 and 6 weeks' post-treatment. The levels of serum
      bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP-5b),
      and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were
      significantly reduced after 3 and 6 weeks' post-treatment (P < .001). Aside from
      a few adverse events, no liver or renal toxicity was observed. Bone metabolism
      markers decreased by varying degrees after treatment with a loading dose of
      ibandronate in patients with BM from breast cancer. It might be convenient using
      bone metabolism markers to potentially evaluate the efficacy of bisphosphonates
      treatment for bone metastasis.

PMID- 27716994
TI  - Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex
      different manner.
AB  - Pain is a complex and subjective experience. Previous studies have shown that
      mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a
      role of the D3 receptor in modulation of nociception. Given that there are sex
      differences in pain perception, there may be differences in responses to
      nociceptive stimuli between male and female D3RKO mice. In the current study, we
      examined the role of the D3 receptor in modulating nociception in male and female
      D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test was
      performed at different temperatures including 52 degrees C, 55 degrees C, and 58
      degrees C. The von Frey hair test was applied to evaluate mechanical pain. And
      persistent pain produced by peripheral tissue injury and inflammation was modeled
      by formalin test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO
      mice generally exhibited longer latencies at each of the three temperatures.
      Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when the
      temperature was 55 degrees C, while for the female mice, there was a statistical
      difference between genotypes when the test condition was 52 degrees C. In the von
      Frey hair test, both male and female D3RKO mice exhibited hypoalgesia. In the
      formalin test, the male D3RKO mice displayed a similar nociceptive behavior as
      their sex-matched WT littermates, whereas significantly depressed late-phase
      formalin-induced nociceptive behaviors were observed in the female mutants. These
      findings indicated that the D3 receptor affects nociceptive behaviors in a sex
      specific manner and that its absence induces more analgesic behavior in the
      female knockout mice. (c) 2016 Wiley Periodicals, Inc.

PMID- 27716996
TI  - The transcription factor cyclic adenosine 3',5'-monophosphate response element
      binding protein enhances the odonto/osteogenic differentiation of stem cells from
      the apical papilla.
AB  - AIM: To investigate the role of cAMP response element-binding protein (CREB) in
      the regulation of odonto/osteogenic differentiation of stem cells from the apical
      papilla (SCAPs). METHODOLOGY: Stem cells from the apical papilla were obtained
      from human impacted third molars (n = 15). Isolated SCAPs were transfected with
      CREB overexpressing/silenced lentivirus. Transfected cells were stained with
      alizarin red to investigate mineralized nodule formation. The expression of the
      mineralization-related genes, alkaline phosphatase (ALP), collagen type I (Col
      I), runt-related transcription factor 2 (RUNX2), osterix (OSX) and osteocalcin
      (OCN), was determined by quantitative reverse transcription polymerase chain
      reaction (qRT-PCR). Protein expression of the odontogenic-related marker dentine
      sialoprotein (DSP) and the osteogenic-related marker RUNX2 was measured by
      Western blotting analysis. One-way analysis of variance (anova) and Student's t
      test were used for statistical analysis (a = 0.05). RESULTS: The overexpression
      of CREB enhanced mineralized nodule formation and up-regulated (P < 0.05) the
      mRNA levels of odonto/osteogenic-related markers, including ALP, Col I, RUNX2,
      OSX and OCN, and also increased (P < 0.05) the protein expression of DSP and
      RUNX2. In contrast, the silencing of CREB inhibited (P < 0.05) the mineralization
      capacity of the SCAPs and decreased (P < 0.05) the expression of
      odonto/osteogenic-related markers. CONCLUSION: Up-regulation of CREB expression
      promoted odonto/osteogenic differentiation of SCAPs and provided a potential
      method for the regeneration of the dentine-pulp complex.

PMID- 27716997
TI  - Establishment of reference intervals for serum thyroid-stimulating hormone, free
      and total thyroxine, and free and total triiodothyronine for the Beckman Coulter
      DxI-800 analyzers by indirect method using data obtained from Chinese population
      in Zhejiang Province, China.
AB  - BACKGROUND: In order to establish suitable reference intervals of thyroid
      stimulating hormone (TSH), free (unbound) T4 (FT4), free triiodothyronine (FT3),
      total thyroxine (T4), and total triiodothyronine (T3) for the patients collected
      in Zhejiang, China, an indirect method was developed using the data from the
      people presented for routine health check-up. METHODS: Fifteen thousand nine
      hundred and fifty-six person's results were reviewed. Box-Cox or Case Rank was
      used to transform the data to normal distribution. Tukey and Box-Plot methods
      were used to exclude the outliers. Nonparametric method was used to establish the
      reference intervals following the EP28-A3c guideline. Pearson correlation was
      used to evaluate the correlation between hormone levels and age, while Mann
      Whitney U test was employed for quantification of concentration differences on
      the people who are younger and older than 50 years old. RESULTS: Reference
      intervals were 0.66-4.95 mIU/L (TSH), 8.97-14.71 pmol/L (FT4), 3.75-5.81 pmol/L
      (FT3), 73.45-138.93 nmol/L (total T4), and 1.24-2.18 nmol/L (total T3) in male;
      conversely, reference intervals for female were 0.72-5.84 mIU/L (TSH), 8.62-14.35
      pmol/L (FT4), 3.59-5.56 pmol/L (FT3), 73.45-138.93 nmol/L (total T4), and 1.20
      2.10 nmol/L (total T3). FT4, FT3, and total T3 levels in male and FT4 level in
      female had an inverse correlation with age. Total T4 and TSH levels in female
      were directly correlated. Significant differences in these hormones were also
      found between younger and older than 50 years old except FT3 in female.
      CONCLUSIONS: Indirect method can be applied for establishment of reference
      intervals for TSH, FT4, FT3, total T4, and total T3. The reference intervals are
      narrower than those previously established. Age factor should also be considered.

PMID- 27716998
TI  - Viewing distance and eyestrain symptoms with prolonged viewing of smartphones.
AB  - BACKGROUND: This paper investigates viewing distances and eyestrain symptoms in
      young adults reading from a smartphone for 60 minutes. METHODS: A survey related
      to common asthenopic (eyestrain) symptoms was administered to subjects before and
      after they read an extract from a novel on a smartphone for 60 minutes. Subjects
      rated their symptoms on a scale from zero (not at all) to four (extremely). The
      viewing distance to the smartphone was measured on a photograph taken of the
      subject every minute. Each subject used the same smartphone and read the same
      text. RESULTS: Subjects were 18 young adults (mean age: 21.5 +/- 3.3 years) with
      self-reported good health, normal visual acuity and no accommodative or binocular
      vision disorders. The mean viewing distance while using a smartphone over 60
      minutes was 29.2 +/- 7.3 cm. The viewing distance was significantly greater
      during the first, second and fifth 10-minute time periods (30.6 +/- 7.2 cm, 29.7
      +/- 7.3 cm and 28.9 +/- 8.5 cm, respectively) than during the final 10-minute
      time period (27.8 +/- 7.7 cm) (Wilcoxon, p = 0.023, 0.02 and 0.04, respectively).
      The total symptom score was significantly greater post-experiment (score = 8.06)
      than pre-experiment (score = 3.56) (Wilcoxon, p < 0.001). Symptoms of tired eyes,
      uncomfortable eyes and blur increased significantly after 60 minutes of
      smartphone use (Wilcoxon, p < 0.05). There was a significant correlation between
      change in total symptom score and change in viewing distance (rho = -0.51; p =
      0.03). The only single symptom that correlated with a change in viewing distance
      was 'uncomfortable eyes' (rho = -0.52, p = 0.03). CONCLUSION: Viewing distances
      are closer and eyestrain symptoms are greater after reading from a smartphone for
      60 minutes. The viewing distances measured were closer than those previously
      reported in the literature.

PMID- 27716995
TI  - UV-Induced DNA Damage and Mutagenesis in Chromatin.
AB  - UV radiation induces photolesions that distort the DNA double helix and, if not
      repaired, can cause severe biological consequences, including mutagenesis or cell
      death. In eukaryotes, both the formation and repair of UV damage occur in the
      context of chromatin, in which genomic DNA is packaged with histones into
      nucleosomes and higher order chromatin structures. Here, we review how chromatin
      impacts the formation of UV photoproducts in eukaryotic cells. We describe the
      initial discovery that nucleosomes and other DNA binding proteins induce
      characteristic "photofootprints" during the formation of UV photoproducts. We
      also describe recent progress in genomewide methods for mapping UV damage, which
      echoes early biochemical studies, and highlights the role of nucleosomes and
      transcription factors in UV damage formation and repair at unprecedented
      resolution. Finally, we discuss our current understanding of how the distribution
      and repair of UV-induced DNA damage influence mutagenesis in human skin cancers.

PMID- 27716999
TI  - A Rare Case of Pembrolizumab-Induced Uveitis in a Patient with Metastatic
      Melanoma.
AB  - Pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, is a humanized
      monoclonal antibody used in the treatment of metastatic or unresectable melanoma
      and advanced non-small cell lung cancer (NSCLC). We hereby report a case of
      pembrolizumab-induced uveitis to increase practitioner awareness. A 78-year-old
      woman presented with onset of panuveitis after initiation of pembrolizumab
      therapy for metastatic melanoma. The patient received three cycles of therapy
      every 21 days, during which her symptoms progressively worsened. She was treated
      with topical and systemic corticosteroids, and further pembrolizumab was
      discontinued despite a good response to therapy. Pembrolizumab has been
      associated with rapid onset of ocular inflammation and uveitis. PD-1 inhibitors
      mediate a T-cell response against cancer cells; however, autoimmune complications
      have been reported. Incidence of pembrolizumab-induced uveitis is reported to be
      < 1%. To date, three cases have been reported since its Food and Drug
      Administration approval in September 2014. Uveitis, if left untreated, may lead
      to permanent vision loss and ocular damage. Cases of immune-mediated uveitis have
      been reported with cancer immunotherapies. Oncologists and ophthalmologists
      should be aware of this complication. With the increasing targeted
      pharmaceuticals in oncology, effective management of adverse events is necessary
      to ensure patient safety and optimal outcomes.

PMID- 27717000
TI  - Elongation of SIEV using SCIV in breast reconstruction with an SIEA flap.

PMID- 27717001
TI  - High-accuracy modeling of antibody structures by a search for minimum-energy
      recombination of backbone fragments.
AB  - Current methods for antibody structure prediction rely on sequence homology to
      known structures. Although this strategy often yields accurate predictions,
      models can be stereo-chemically strained. Here, we present a fully automated
      algorithm, called AbPredict, that disregards sequence homology, and instead uses
      a Monte Carlo search for low-energy conformations built from backbone segments
      and rigid-body orientations that appear in antibody molecular structures. We find
      cases where AbPredict selects accurate loop templates with sequence identity as
      low as 10%, whereas the template of highest sequence identity diverges
      substantially from the query's conformation. Accordingly, in several cases
      reported in the recent Antibody Modeling Assessment benchmark, AbPredict models
      were more accurate than those from any participant, and the models' stereo
      chemical quality was consistently high. Furthermore, in two blind cases provided
      to us by crystallographers prior to structure determination, the method achieved
      <1.5 Angstrom overall backbone accuracy. Accurate modeling of unstrained antibody
      structures will enable design and engineering of improved binders for biomedical
      research directly from sequence. Proteins 2016; 85:30-38. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27717002
TI  - Impact of Travel Distance and Urban-Rural Status on the Multidisciplinary
      Management of Rectal Cancer.
AB  - OBJECTIVES: Optimal treatment of rectal cancer (RC) requires multidisciplinary
      care. We examined whether distance to treatment center or community size impacts
      access to multimodality care and population-based outcomes in RC. METHODS:
      Patients diagnosed with stage II/III RC from 1999 to 2009 and treated at 1 of 6
      regional cancer centers in British Columbia were reviewed. Distance to treatment
      center was determined for each patient. Communities were classified as rural,
      small, medium, and large population centers. Logistic and Cox regression models
      assessed associations of distance and community size with treatment received as
      well as cancer-specific (CSS) and overall survival (OS). RESULTS: Of 3,158
      patients, 93.6% underwent surgery, 86.3% received radiotherapy, and 51.3% were
      treated with adjuvant chemotherapy (AC). Median time from diagnosis to oncologic
      consultation was longer for those >100 km from a treatment center or residing in
      medium/rural communities. Logistic regression demonstrated no correlation between
      distance or community size and receipt of treatment modality. Univariate analysis
      showed similar CSS (P = .18, .88) and OS (P = .36, .47) based on community size
      and distance, respectively. In multivariate analysis, distance >100 km had
      inferior CSS (Hazard Ratio [HR] 1.39, 95% CI: 1.03-1.88; P = .031). There was no
      consistent trend between decreasing community size and outcomes; however, living
      in a small center was associated with improved OS (HR 0.58, 95% CI: 0.38-0.88; P
      = .011) and CSS (HR 0.42, 95% CI: 0.25-0.70; P = .001). CONCLUSIONS: In this
      population-based study, there were no urban-rural differences in access to
      multidisciplinary care, but increased distance may be associated with worse
      cancer-specific outcomes.

PMID- 27717003
TI  - A Brazilian Investigation of the 36- and 16-Item Difficulties in Emotion
      Regulation Scales.
AB  - OBJECTIVE: About 10 years ago, Gratz and Roemer (2004) introduced the
      Difficulties in Emotion Regulation Scale (DERS), a 36-item self-report instrument
      measuring 6 areas of emotion regulation problems. Recently, Bjureberg et al.
      (2015) have introduced a new, briefer version of the DERS comprising only 16 of
      the 36 items included in the original version. Because no studies have yet cross
      validated the recently introduced 16-item DERS and the 36-item DERS has never
      been tested in Brazil, we sought to inspect the psychometric properties of scores
      from both DERS versions with a nonclinical Brazilian sample. METHOD: Participants
      were 725 adult volunteers aged 18-70 years (mean = 30.54, standard deviation =
      10.59), 82.3% of whom were women. All were administered the DERS along with a
      number of other self-report and performance-based instruments. Data analyses
      inspected internal consistency, factor structure, and convergent as well as
      divergent validity of scores from both DERS versions. RESULTS: Results show that
      scores from both DERS versions possess good psychometric properties.
      Interestingly, both versions correlated, in the expected direction, with
      psychopathology and showed no significant correlations with cognitive measures.
      Like in other studies, however, the Awareness factor of the 36-item DERS did not
      produce optimal validity and reliability indexes. CONCLUSION: Taken together, our
      findings indicate that the 16-item DERS may be preferred over the 36-item version
      and provide additional support to the differentiation between emotion regulation
      and cognitive tasks of emotional perception and abstract and verbal reasoning.

PMID- 27717004
TI  - Mutations in idiopathic cytopenia of undetermined significance assist diagnostics
      and correlate to dysplastic changes.
AB  - Cytopenia is common in the elderly population and etiology may be difficult to
      assess. Here, we investigated the occurrence of mutations in patients with
      idiopathic cytopenia of undetermined significance and the usefulness in improving
      diagnostics. We included 60 patients with persistent cytopenia > 6 months without
      definite diagnosis of hematological neoplasm after routine assessment. Bone
      marrow material underwent a blinded morphology review and DNA was sequenced with
      a targeted 20 gene panel representing the most commonly mutated genes in
      myelodysplastic syndrome. Thirty seven (62%) patients carried at least one
      mutation at inclusion, and of these 95% carried a mutation in TET2, ASXL1, SRSF2,
      or DNMT3A. The most commonly mutated gene was TET2 observed in 43% of all
      patients. During one to eight years follow-up seven patients progressed to a
      myeloid neoplasm and six of these had a detectable mutation at study entry.
      Median time to progression was 53 months (range 10-78), and at time of
      progression each patient had at least two mutations detected. Mutations in TP53
      and NRAS were not present in patients at inclusion, but identified as secondary
      hits triggering progression. The morphology review was concordant in 68% of all
      cases, and 93% of the cases reclassified into the group "highly suspicious for
      MDS" had a mutation. All patients who had a concordant review "highly suspicious
      for MDS" had at least two mutations detected. Overall, we show that morphology
      examination is challenging in this heterogeneous group and targeted sequencing
      helps identify patients at risk of progression. Am. J. Hematol. 91:1234-1238,
      2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27717006
TI  - Commodifying Indigeneity: How the Humanization of Birth Reinforces Racialized
      Inequality in Mexico.
AB  - This article examines the humanized birth movement in Mexico and analyzes how the
      remaking of tradition-the return to traditional birthing arts (home birth,
      midwife-assisted birth, natural birth)-inadvertently reinscribes racial
      hierarchies. The great irony of the humanized birth movement lies in parents'
      perspective of themselves as critics of late capitalism. All the while, their
      very rejection of consumerism bolsters ongoing commodification of indigenous
      culture and collapses indigeneity, nature, and tradition onto one another. While
      the movement is quickly spreading across Mexico, indigenous women and their
      traditional midwives are largely excluded from the emerging humanized birth
      community. Through ethnographic examples, the article suggests that indigenous
      individuals are agentive actors who appropriate cards in decks stacked against
      them. Examples of resistance emerge within a context of power and political
      economy that often capitalizes on images of indigeneity while obscuring the
      lives, experiences, and opinions of indigenous people.

PMID- 27717007
TI  - Provisional epidemiological cutoff values for standard broth microdilution
      susceptibility testing of Flavobacterium columnare.
AB  - The gliding aquatic bacterium Flavobacterium columnare causes columnaris disease,
      a common problem for wild and farmed freshwater fish worldwide. Recently, a broth
      microdilution method was standardized to test the susceptibility of F. columnare
      against antimicrobials commonly used in aquaculture. We used this new method to
      measure the minimal inhibitory concentrations (MICs) of ten antimicrobials
      against 120 F. columnare isolates. The resulting MIC frequency distributions for
      each antimicrobial (1 MIC/isolate) were used to estimate epidemiological cut-off
      values (ECVs) which separate isolates with typical wild-type (WT) susceptibility
      from isolates with decreased non-wild-type (NWT) susceptibility. We identified 22
      NWT isolates with elevated MICs relative to the ECV that covered 99.9% of the MIC
      distribution against one or more of the antimicrobials: ampicillin, enrofloxacin,
      erythromycin, florfenicol, flumequine, oxolinic acid or oxytetracycline. Ten of
      the NWT isolates had decreased susceptibility to a single antimicrobial class,
      six isolates to two antimicrobial classes and six isolates to three or more
      antimicrobial classes. The MIC frequency distributions and provisional cut-off
      values provide data needed to set epidemiological cut-off values to monitor for
      the development of antimicrobial resistance among F. columnare.

PMID- 27717008
TI  - 'Hints' in the horn: diagnostic clues in the stratum corneum.
AB  - The stratum corneum or horny layer is the uppermost layer of the epidermis, and
      is mainly responsible for the skin's barrier function. In spite of its complexity
      at the ultrastructural and molecular level, the features accessible to
      visualization on conventional histology are relatively limited. Nevertheless,
      knowledge of subtle clues that one may observe in the stratum corneum can prove
      useful in a wide range of situations in dermatopathology. We herein review a
      selection of common and rare entities in which the horny layer may reveal
      significantly important hints for the diagnosis. These clues include
      parakeratosis and its different patterns (focal, confluent, alternating,
      associated with spongiosis, epidermal hyperplasia or lichenoid changes),
      subcorneal acantholysis, infectious organisms in the stratum corneum (including
      fungal, bacterial and parasitic), thickening or thinning of the stratum corneum
      and the presence of different kinds of pigment. Even when normal, the horny layer
      may prove to be useful when seen in association with severe epidermal damage, a
      combination of features testifying to the acute nature of the underlying
      pathological process.

PMID- 27717005
TI  - Specifically neuropathic Gaucher's mutations accelerate cognitive decline in
      Parkinson's.
AB  - OBJECTIVE: We hypothesized that specific mutations in the beta-glucocerebrosidase
      gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to
      aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients,
      whereas non-neuropathic GD mutations confer intermediate progression rates.
      METHODS: A total of 2,304 patients with PD and 20,868 longitudinal visits for up
      to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential
      effects of four types of genetic variation in GBA on longitudinal cognitive
      decline were evaluated using mixed random and fixed effects and Cox proportional
      hazards models. RESULTS: Overall, 10.3% of patients with PD and GBA sequencing
      carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had
      hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence
      interval [CI], 1.60-6.25) and a hastened decline in Mini-Mental State Exam scores
      compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had
      an HR of 3.22 (95% CI, 1.18-8.73; p = 0.022). By contrast, the common, non
      neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92-4.18) or
      nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89-2.05) did
      not reach significance. INTERPRETATION: Mutations in the GBA gene pathogenic for
      neuropathic GD and complex alleles shift longitudinal cognitive decline in PD
      into "high gear." These findings suggest a relationship between specific types of
      GBA mutations and aggressive cognitive decline and have direct implications for
      improving the design of clinical trials. Ann Neurol 2016;80:674-685.

PMID- 27717009
TI  - Considering the needs of indigenous and local populations in conservation
      programs.
AB  - Local rural and indigenous communities have assumed increasing responsibility for
      conservation within and between areas buffering the impacts of agricultural or
      resource-extraction zones and protected areas. Empowering local communities as
      central partners in conservation and climate-change mitigation has allowed many
      people to gain access to land and citizenship rights but has provided limited
      improvements in access to social services and economic opportunities even as
      expectation about their role as environmental stewards grows. These expectations,
      however, are inconsistent with reality. We conducted multiple field studies in
      Brazil since the mid-1980s to illustrate the discrepancies between conservation
      programs and local conditions and expectations. We suggest that public policies
      and conservation programs should not delegate responsibility for managing
      protected areas to local and indigenous communities without considering local
      needs and expectations and locals' attitudes toward conservation. In other words,
      behavior that maintains or improves the environment should not be treated as
      traditional based on the expectations of outsiders. Framing local populations as
      traditional environmentalists creates contradictions and frustrations for local
      populations and for conservation professionals and policy makers.

PMID- 27717010
TI  - Reconfigurable Nonvolatile Logic Operations in Resistance Switching Crossbar
      Array for Large-Scale Circuits.
AB  - Resistance switching (RS) devices have potential to offer computing and memory
      function. A new computer unit is built of RS array, where processing and storing
      of information occur on same devices. Resistance states stored in devices located
      in arbitrary positions of RS array can be performed various nonvolatile logic
      operations. Logic functions can be reconfigured by altering trigger signals.

PMID- 27717011
TI  - Electrical Energy Generation via Reversible Chemical Doping on Carbon Nanotube
      Fibers.
AB  - Chemically modified carbon nanotube fibers enable unique power sources driven
      entirely by a chemical potential gradient. Electrical current (11.9 MUA mg-1 )
      and potential (525 mV) are reversibly produced by localized acetonitrile doping
      under ambient conditions. An inverse length-scaling of the maximum power as L
      1.03 that creates specific powers as large as 30.0 kW kg-1 highlights the
      potential for microscale energy generation.

PMID- 27717013
TI  - Increased troponin I is associated with fatal outcome in acquired thrombotic
      thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) has >90% mortality without therapeutic
      plasma exchange (TPE). Despite TPE, approximately 10% of patients still die,
      presumably from cardiac ischemia. We sought clinical or laboratory parameters
      associated with death by reviewing the records of all patients hospitalized with
      acquired TTP in our institution for 10 years, and collect demographics and
      results for hemoglobin, platelet count, creatinine, lactate dehydrogenase,
      transaminases, total bilirubin, creatinine kinase (CK), CK-MB, and troponin I.
      Sixty-eight patients were admitted 88 times, and 11 died. Survivors and non
      survivors were similar in terms of sex, ethnicity, thrombocytopenia, and degree
      of anemia at presentation, while the latter were older, had worse renal function
      and higher CK, CK-MB, and troponin I (univariate analysis). However, only
      troponin I remained significant on multivariate analyses. We propose that
      patients with TTP should be monitored with troponin I to detect significant
      myocardial ischemia that could predict death despite TPE.

PMID- 27717012
TI  - Histone deacetylase inhibitors for cancer therapy: An evolutionarily ancient
      resistance response may explain their limited success.
AB  - Histone deacetylase inhibitors (HDACi) are in clinical trials against a variety
      of cancers. Despite early successes, results against the more common solid tumors
      have been mixed. How is it that so many cancers, and most normal cells, tolerate
      the disruption caused by HDACi-induced protein hyperacetylation? And why are a
      few cancers so sensitive? Here we discuss recent results showing that human cells
      mount a coordinated transcriptional response to HDACi that mitigates their toxic
      effects. We present a hypothetical signaling system that could trigger and
      mediate this response. To account for the existence of such a response, we note
      that HDACi of various chemical types are made by a variety of organisms to kill
      or suppress competitors. We suggest that the resistance response in human cells
      is a necessary evolutionary consequence of exposure to environmental HDACi. We
      speculate that cancers sensitive to HDACi are those in which the resistance
      response has been compromised by mutation. Identifying such mutations will allow
      targeting of HDACi therapy to potentially susceptible cancers. Also see the video
      abstract here.

PMID- 27717014
TI  - Use of direct-acting agents for hepatitis C virus-positive kidney transplant
      candidates and kidney transplant recipients.
AB  - In some parts of the world, hepatitis C virus (HCV) infection remains a huge
      problem for kidney transplant candidates and kidney transplant (KT) recipients.
      Until 2 years ago, anti-HCV treatment for the general population relied on
      pegylated alpha-interferon plus ribavirin, but led to a sustained viral response
      (SVR) in <50% of cases. This treatment was contraindicated in KT patients because
      of acute-rejection issues and was poorly tolerated in patients with end-stage
      renal disease (ESRD). Over the last year, direct-acting antiviral agents (DAAs)
      have entered the market and are associated in the general population with a SVR
      of >90%, whatever the patient's HCV genotype. In KT patients, sofosbuvir-based
      therapy is associated with a SVR at nearly 100% in patients with a HCV genotype-1
      infection, with almost no side effects and only mild interference with
      immunosuppressive drugs. Most HCV(+) patients with ESRD are genotype 1: in that
      setting, a recent study reported that the association of grazoprevir/elbasvir
      100/50 mg/day led to a SVR of nearly 95% with very few side effects. Thus, it is
      concluded that DAAs can be safely used and lead to results in KT candidates and
      KT patients that are as good as those observed in the nonrenal population.

PMID- 27717016
TI  - An acneiform eruption exhibiting locus minoris resistentiae after whole-brain
      radiation and vemurafenib therapy.

PMID- 27717015
TI  - Regulatory B10 cells display an altered homoeostasis in acute graft-versus-host
      disease.
AB  - OBJECTIVE: The role of B cells and the subgroup of IL-10 producing B cells, known
      to have a regulatory function, in patients following a haematopoietic stem cell
      transplant (alloSCT) has not been clearly understood to date. METHODS: We
      prospectively recruited 95 patients following an alloSCT and studied the B-cell
      reconstitution on days 30, 90 and 150. Regulatory B10 cells could be analysed in
      22 consecutively recruited patients on day 30 post-transplant. RESULTS: The total
      B-cell percentages in transplant recipients (median 0.33; range 0.01-5.9) were
      significantly reduced than the controls (P = 0.0001) and constituted
      predominantly of transitional CD24high CD38high B cells. Regulatory B10 cells
      could be analysed in 22 consecutively recruited patients on day 30 post
      transplant. The percentages of B10 cells (median 1.35; 0.0-4.5) were
      significantly reduced in the transplant recipients in comparison with the control
      cohort (P < 0.0001). Interestingly, the percentages of B10 cells in patients with
      acute GvHD (median 1.7; 0.33-4.5) were significantly higher than those without
      GvHD (median 0.7; 0-1.9) (P = 0.0003). CONCLUSION: This is the first report
      demonstrating B10 cells in stem cell transplant recipients in the early post
      alloSCT (30 d) period. Our data suggest a possible role for B10 cells in the
      pathophysiology of acute GvHD. Further longitudinal studies are warranted to
      understand the implications of our findings.

PMID- 27717017
TI  - Five-year follow-up after live donor nephrectomy - cross-sectional and
      longitudinal analysis of a prospective cohort within the era of extended donor
      eligibility criteria.
AB  - To establish the outcome of live kidney donors 5 years after donation, we
      investigated the risk for progressive renal function decline and quality of life
      (QoL). Data on estimated glomerular filtration rate (eGFR), creatinine,
      hypertension, QoL and survival were assessed in a prospective cohort of 190
      donors, who donated between 2008 and 2010. Data were available for >90%. The mean
      age predonation was 52.8 +/- 11.5 years, 30 donors having pre-existent
      hypertension. The mean follow-up was 5.1 +/- 0.9 years. Eight donors had died due
      to non-donation-related causes. After 5 years, the mean eGFR was 60.2 (95% CI
      58.7-62.7) ml/min/1.73 m2 , with a median serum creatinine of 105.1 (95% CI 102.5
      107.8) MUmol/l. eGFR decreased to 33.6% and was longitudinally lower among men
      than women and declining with age (P < 0.001), without any association on QoL.
      Donors with pre-existent and new-onset hypertension demonstrated no progressive
      decline of renal function overtime compared to nonhypertensives. No donors were
      found with proteinuria, microalbuminuria or at risk for end-stage renal disease.
      After an initial decline postdonation, renal function remained unchanged
      overtime. Men and ageing seem to affect renal function overtime, while decreased
      renal function did not affect QoL. These data support further stimulation of
      living kidney donation programmes as seen from the perspective of donor safety.

PMID- 27717018
TI  - Efficient and Stable White LEDs with Silica-Coated Inorganic Perovskite Quantum
      Dots.
AB  - A white light-emitting diode (0.33, 0.33) is fabricated using perovskite quantum
      dot/silica composites. It is shown to have greatly improved stability.

PMID- 27717019
TI  - Lipid profile in patients with androgenetic alopecia: a meta-analysis.
AB  - BACKGROUND: Many studies have reported that androgenetic alopecia (AGA) might be
      a risk factor for cardiovascular disorders, and the association of AGA with
      dyslipidaemia has been studied. However, the results were controversial and
      previous meta-analyses had several critical limitations. OBJECTIVE: We performed
      a meta-analysis to clarify whether AGA patients have abnormal lipid profiles.
      METHODS: A literature search was performed using the MEDLINE, EMBASE, The
      Cochrane Library and KOREA MED databases. RESULTS: We pooled 19 observational
      studies and performed a meta-analysis to compare serum total cholesterol, serum
      triglyceride (TG), low-density lipoprotein (LDL) cholesterol and high-density
      lipoprotein (HDL) and the cholesterol levels between AGA and control groups. The
      serum total cholesterol, TG and LDL cholesterol levels were significantly higher
      in the AGA group than in the control group, and the standardized mean differences
      were 0.377 (95% confidence interval [CI]: 0.182-0.572, P < 0.001), 0.426 (95% CI:
      0.164-0.688, P = 0.001) and 0.450 (95% CI: 0.171-0.728, P = 0.002) respectively.
      In addition, HDL cholesterol level was significantly lower in the AGA group than
      in the control group, and the standardized mean difference was -0.248 (95% CI: 
      0.472 to -0.023, P = 0.030). CONCLUSIONS: AGA patients showed statistically
      significant abnormal lipid profiles, and this might partly explain the
      association between AGA and cardiovascular diseases.

PMID- 27717020
TI  - Does nitrogen affect the interaction between a native hemiparasite and its native
      or introduced leguminous hosts?
AB  - Associations between plants and nitrogen (N)-fixing rhizobia intensify with
      decreasing N supply and come at a carbon cost to the host. However, what
      additional impact parasitic plants have on their leguminous hosts' carbon budget
      in terms of effects on host physiology and growth is unknown. Under glasshouse
      conditions, Ulex europaeus and Acacia paradoxa either uninfected or infected with
      the hemiparasite Cassytha pubescens were supplied (high nitrogen (HN)) or not
      (low nitrogen (LN)) with extra N. The photosynthetic performance and growth of
      the association were measured. Cassytha pubescens significantly reduced the
      maximum electron transport rates and total biomass of U. europaeus but not those
      of A. paradoxa, regardless of N. Infection significantly decreased the root
      biomass of A. paradoxa only at LN, while the significant negative effect of
      infection on roots of U. europaeus was less severe at LN. Infection had a
      significant negative impact on host nodule biomass. Ulex europaeus supported
      significantly greater parasite biomass (also per unit host biomass) than A.
      paradoxa, regardless of N. We concluded that rhizobia do not influence the effect
      of a native parasite on overall growth of leguminous hosts. Our results suggest
      that C. pubescens will have a strong impact on U. europaeus but not A. paradoxa,
      regardless of N in the field.

PMID- 27717021
TI  - Do shoot the messenger: Taking aim at RNA to treat genetic skin disorders.

PMID- 27717022
TI  - Controlling Chain Conformations of High-k Fluoropolymer Dielectrics to Enhance
      Charge Mobilities in Rubrene Single-Crystal Field-Effect Transistors.
AB  - A novel photopatternable high-k fluoropolymer, poly(vinylidene fluoride
      bromotrifluoroethylene) P(VDF-BTFE), with a dielectric constant (k) between 8 and
      11 is demonstrated in thin-film transistors. Crosslinking P(VDF-BTFE) reduces
      energetic disorder at the dielectric-semiconductor interface by controlling the
      chain conformations of P(VDF-BTFE), thereby leading to approximately a threefold
      enhancement in the charge mobility of rubrene single-crystal field-effect
      transistors.

PMID- 27717024
TI  - Plants are less negatively affected by flooding when growing in species-rich
      plant communities.
AB  - Flooding is expected to increase in frequency and severity in the future. The
      ecological consequences of flooding are the combined result of species-specific
      plant traits and ecological context. However, the majority of past flooding
      research has focused on individual model species under highly controlled
      conditions. An early summer flooding event in a grassland biodiversity experiment
      in Jena, Germany, provided the opportunity to assess flooding responses of 60
      grassland species in monocultures and 16-species mixtures. We examined plant
      biomass, species-specific traits (plant height, specific leaf area (SLA), root
      aerenchyma, starch content) and soil porosity. We found that, on average, plant
      species were less negatively affected by the flood when grown in higher-diversity
      plots in July 2013. By September 2013, grasses were unaffected by the flood
      regardless of plant diversity, and legumes were severely negatively affected
      regardless of plant diversity. Plants with greater SLA and more root aerenchyma
      performed better in September. Soil porosity was higher in higher-diversity plots
      and had a positive effect on plant performance. As floods become more frequent
      and severe in the future, growing flood-sensitive plants in higher-diversity
      communities and in soil with greater soil aeration may attenuate the most
      negative effects of flooding.

PMID- 27717026
TI  - Epidemiology of bloodstream infections in patients with myeloma receiving current
      era therapy.
AB  - BACKGROUND: Bloodstream infections (BSIs) are a significant complication of
      treatment for multiple myeloma (MM). The objective of this study was to define
      the epidemiology of BSI with current era MM treatment regimens, including
      immunomodulatory drugs, proteasome inhibitors and autologous haematopoietic stem
      cell transplantation (ASCT). METHODS: Clinical and microbiology records of
      patients with MM diagnosed between 2008 and 2012 were reviewed using a
      standardised tool to capture patient demographics, myeloma characteristics and
      BSI characteristics (type, severity, outcomes). Conditional risk set modelling
      was used to determine clinical predictors of BSI. RESULTS: Of 199 studied
      patients, 71 (35.6%) had confirmed BSI (98 infection episodes). Peak incidence
      was 65.1 infections/100 patient-years at 4-6 months following MM diagnosis with a
      late peak at 64-66 months. Gram-positive pathogens were responsible for the
      majority (54.5%) of infections during induction, whilst gram-negative pathogens
      were responsible for the majority (57.7%) of infections during disease
      progression. Overall, Escherichia coli was the most frequently identified
      pathogen. Streptococcus pneumoniae comprised 6.1% of all BSIs at a median of 7.5
      months following MM diagnosis. Highest rates of ICU admission (23.1%) and
      mortality (11.5%) were seen with BSIs in patients with progressive disease.
      Recent ASCT was independently associated with increased BSI risk (HR 3.09, P =
      0.05). CONCLUSIONS: Treatment of progressive disease is a high-risk period for
      infection, evidenced by high proportions of BSI due to gram-negative pathogens
      and S. pneumoniae. Targeted evaluation of preventative strategies (prophylaxis,
      vaccination) to reduce morbidity and mortality during this period is required.

PMID- 27717025
TI  - Determining donor-specific antibody C1q-binding ability improves the prediction
      of antibody-mediated rejection in human leucocyte antigen-incompatible kidney
      transplantation.
AB  - Detrimental impact of preformed donor-specific antibodies (DSAs) against human
      leucocyte antigens on outcomes after kidney transplantation are well documented,
      however, the value of their capacity to bind complement for predicting antibody
      mediated rejection (AMR) and graft survival still needs to be confirmed. We aimed
      to study DSA characteristics (strength and C1q binding) that might distinguish
      harmful DSA from clinically irrelevant ones. We retrospectively studied 60 kidney
      transplanted patients with preformed DSA detected by single antigen bead (SAB)
      assays (IgG and C1q kits), from a cohort of 517 kidney graft recipients (124 with
      detectable anti-HLA antibodies). Patients were divided into DSA strength (MFI <
      vs. >= 15 000) and C1q-binding ability. AMR frequency was high (30%) and it
      increased with DSA strength (P = 0.002) and C1q+ DSA (P < 0.001). The performance
      of DSA C1q-binding ability as a predictor of AMR was better than DSA strength
      (diagnostic odds ratio 16.3 vs. 6.4, respectively). Furthermore, a multivariable
      logistic regression showed that C1q+ DSA was a risk factor for AMR (OR = 16.80, P
      = 0.001), while high MFI DSAs were not. Graft survival was lower in high MFI C1q+
      DSA in comparison with patients with C1q- high or low MFI DSA (at 6 years, 38%,
      83% and 80%, respectively; P = 0.001). Both DSA strength and C1q-binding ability
      assessment seem valuable for improving pretransplant risk assessment. Since DSA
      C1q-binding ability was a better predictor of AMR and correlated with graft
      survival, C1q-SAB may be a particularly useful tool.

PMID- 27717027
TI  - Strontium Insertion in Methylammonium Lead Iodide: Long Charge Carrier Lifetime
      and High Fill-Factor Solar Cells.
AB  - The addition of Sr2+ in CH3 NH3 PbI3 perovskite films enhances the charge carrier
      collection efficiency of solar cells leading to very high fill factors, up to
      85%. The charge carrier lifetime of Sr2+ -containing perovskites is in excess of
      40 MUs, longer than those reported for perovskite single crystals.

PMID- 27717029
TI  - Safety and effectiveness of extended versus shortened iron dextran infusion time
      for the treatment of iron deficiency anemia.

PMID- 27717028
TI  - Copper-Based Coordination Polymer Nanostructure for Visible Light Photocatalysis.
AB  - An air-stable copper-phenylacetylide nanobelt is synthesized and applied in
      organic pollutants elimination under visible light. Its versatile activity and
      reusability indicate it is a promising photocatalyst, arising from a band gap of
      2.3 eV and the energetically favored electron transfer processes. The tunable
      structures and properties endow copper-based coordination polymers a prosperous
      prospect.

PMID- 27717030
TI  - The Epstein-Barr virus DNA load in the peripheral blood of transplant recipients
      does not accurately reflect the burden of infected cells.
AB  - Transplant recipients frequently exhibit an increased Epstein-Barr virus (EBV)
      load in the peripheral blood. Here, we quantitated the EBV-infected cells in the
      peripheral blood of these patients and defined the mode of viral infection,
      latent or lytic. These data indicated that there is no strong correlation between
      the number of infected cells and the EBV load (EBVL). This can be explained by a
      highly variable number of EBV copies per infected cell and by lytic replication
      in some cells. The plasma of these patients did not contain any free infectious
      viruses, but contained nevertheless EBV DNA, sometimes in large amounts, that
      probably originates from cell debris and contributed to the total EBVL. Some of
      the investigated samples carried a highly variable number of infected cells in
      active latency, characterized by an expression of the Epstein-Barr nuclear
      antigens (EBNA2) protein. However, a third of the samples expressed neither EBNA2
      nor lytic proteins. Patients with an increased EBVL represent a heterogeneous
      group of patients whose infection cannot be characterized by this method alone.
      Precise characterization of the origin of an increased EBVL, in particular, in
      terms of the number of EBV-infected cells, requires additional investigations
      including the number of EBV-encoded small RNA-positive cells.

PMID- 27717031
TI  - A short biography of Jean de Vellis.

PMID- 27717032
TI  - Practical ex-vivo evaluation of application of surgical clips to sutures during
      re-approximation of renal tissue in partial nephrectomy.

PMID- 27717033
TI  - Dithienoindophenines: p-Type Semiconductors Designed by Quinoid Stabilization for
      Solar-Cell Applications.
AB  - Compared with the dominant aromatic conjugated materials, photovoltaic
      applications of their quinoidal counterparts featuring rigid and planar molecular
      structures have long been unexplored despite their narrow optical bandgaps, large
      absorption coefficients, and excellent charge-transport properties. The design
      and synthesis of dithienoindophenine derivatives (DTIPs) by stabilizing the
      quinoidal resonance of the parent indophenine framework is reported here.
      Compared with the ambipolar indophenine derivatives, DTIPs with the fixed
      molecular configuration are found to be p-type semiconductors exhibiting
      excellent unipolar hole mobilities up to 0.22 cm2  V-1  s-1 , which is one order
      of magnitude higher than that of the parent IP-O and is even comparable to that
      of QQT(CN)4-based single-crystal field-effect transistors (FET). DTIPs exhibit
      better photovoltaic performance than their aromatic bithieno[3,4-b]thiophene
      (BTT) counterparts with an optimal power-conversion efficiency (PCE) of 4.07 %.

PMID- 27717034
TI  - Photoelectric Frequency Response in a Bioinspired Bacteriorhodopsin/Alumina
      Nanochannel Hybrid Nanosystem.
AB  - Inspired by the microstructure of rod cell, a bacteriorhodopsin/alumina
      nanochannel hybrid system is demonstrated that converts flickering light impulses
      below 130 Hz into distinguishable patterns of photocurrent to mimic frequency
      responsive characteristic of mammalian retina in vitro. An optimal response
      frequency is identified with unique dependency on bacteriorhodopsin thickness
      rather than the proton concentration gradient and pore size of the alumina
      nanochannel.

PMID- 27717035
TI  - Palatal botulinum toxin as a novel therapy for objective tinnitus in forced
      eyelid closure syndrome.
AB  - Objective tinnitus associated with eyelid closure is a rare clinical entity with
      only a few reported cases. This association previously was identified as forced
      eyelid closure syndrome (FECS) and involves an aberrant neural reflex between
      cranial nerve VII (activating the orbicularis oculi muscle) and cranial nerve V
      (activating the tensor tympani muscle). We present a 52-year-old Caucasian female
      with a 2-month history of FECS who was successfully treated with intrapalatal
      botulinum toxin, with full resolution of her objective tinnitus symptoms. This is
      the first reported use of botulinum toxin in FECS. Laryngoscope, 127:1199-1201,
      2017.

PMID- 27717036
TI  - Lewis Acid Accelerated Aryl Ether Bond Cleavage with Nickel: Orders of Magnitude
      Rate Enhancement Using AlMe3.
AB  - Study of the kinetics of intramolecular aryl ether C-O bond cleavage by Ni was
      facilitated by access to a family of metal complexes supported by diphosphines
      with pendant aryl-methyl ethers. The nature of the aryl substituents was found to
      have little effect on the rate of cleavage. In contrast, soluble Lewis acidic
      additives accelerate the aryl ether cleavage dramatically. The effect of AlMe3
      was studied in detail, and showed an increase in rate by several orders of
      magnitude. Low temperature NMR spectroscopy studies demonstrate quantitative
      coordination of ether to Al. From the Lewis acid-bound precursor, the activation
      parameters for ether cleavage are significantly lower. These findings provide a
      mechanistic basis for milder catalyst design for the activation of strong bonds.

PMID- 27717038
TI  - N-Heterocyclic Olefin-Carbon Dioxide and -Sulfur Dioxide Adducts: Structures and
      Interesting Reactivity Patterns.
AB  - Depending on the amount of methanol present in solution, CO2 adducts of N
      heterocyclic carbenes (NHCs) and N-heterocyclic olefins (NHOs) have been found to
      be in fully reversible equilibrium with the corresponding methyl carbonate salts
      [EMIm][OCO2 Me] and [EMMIm][OCO2 Me]. The reactivity pattern of representative 1
      ethyl-3-methyl-NHO-CO2 adduct 4 has been investigated and compared with the
      corresponding NHC-CO2 zwitterion: The protonation of 4 with HX led to the
      imidazolium salts [NHO-CO2 H][X], which underwent decarboxylation to [EMMIm][X]
      in the presence of nucleophilic catalysts. NHO-CO2 zwitterion 4 can act as an
      efficient carboxylating agent towards CH acids such as acetonitrile. The [EMMIm]
      cyanoacetate and [EMMIm]2 cyanomalonate salts formed exemplify the first C-C bond
      forming carboxylation reactions with NHO-activated CO2 . The reaction of the free
      NHO with dimethyl carbonate selectively led to methoxycarbonylated NHO, which is
      a perfect precursor for the synthesis of functionalized ILs [NHO-CO2 Me][X]. The
      first NHO-SO2 adduct was synthesized and structurally characterized; it showed a
      similar reactivity pattern, which allowed the synthesis of imidazolium methyl
      sulfites upon reaction with methanol.

PMID- 27717037
TI  - Early detection of human glioma sphere xenografts in mouse brain using diffusion
      MRI at 14.1 T.
AB  - Glioma models have provided important insights into human brain cancers. Among
      the investigative tools, MRI has allowed their characterization and diagnosis. In
      this study, we investigated whether diffusion MRI might be a useful technique for
      early detection and characterization of slow-growing and diffuse infiltrative
      gliomas, such as the proposed new models, LN-2669GS and LN-2540GS glioma sphere
      xenografts. Tumours grown in these models are not visible in conventional T2 
      weighted or contrast-enhanced T1 -weighted MRI at 14.1 T. Diffusion-weighted
      imaging and diffusion tensor imaging protocols were optimized for contrast by
      exploring long diffusion times sensitive for probing the microstructural
      alterations induced in the normal brain by the slow infiltration of glioma sphere
      cells. Compared with T2 -weighted images, tumours were properly identified in
      their early stage of growth using diffusion MRI, and confirmed by localized
      proton MR spectroscopy as well as immunohistochemistry. The first evidence of
      tumour presence was revealed for both glioma sphere xenograft models three months
      after tumour implantation, while no necrosis, oedema or haemorrhage were detected
      either by MRI or by histology. Moreover, different values of diffusion indices,
      such as mean diffusivity and fractional anisotropy, were obtained in tumours
      grown from LN-2669GS and LN-2540GS glioma sphere lines. These observations
      highlighted diverse tumour microstructures for both xenograft models, which were
      reflected in histology. This study demonstrates the ability of diffusion MRI
      techniques to identify and investigate early stages of slow-growing, invasive
      tumours in the mouse brain, thus providing a potential imaging biomarker for
      early detection of tumours in humans.

PMID- 27717040
TI  - Stability and Unimolecular Reactivity of Palladate(II) Complexes [Ln PdR3 ]-
      (L=Phosphine, R=Organyl, n=0 and 1).
AB  - The reduction of PdII precatalysts to catalytically active Pd0 species is a key
      step in many palladium-mediated cross-coupling reactions. Besides phosphines, the
      stoichiometrically used organometallic reagents can afford this reduction, but do
      so in a poorly understood way. To elucidate the mechanism of this reaction, we
      have treated solutions of Pd(OAc)2 and a phosphine ligand L in tetrahydrofuran
      with RMgCl (R=Ph, Bn, Bu) as well as other organometallic reagents. Analysis of
      these model systems by electrospray- ionization mass spectrometry found
      palladate(II) complexes [Ln PdR3 ]- (n=0 and 1), thus pointing to the occurrence
      of transmetallation reactions. Upon gas-phase fragmentation, the [Ln PdR3 ]-
      anions preferentially underwent a reductive elimination to yield Pd0 species. The
      sequence of the transmetallation and reductive elimination, thus, constitutes a
      feasible mechanism for the reduction of the Pd(OAc)2 precatalyst. Other species
      of interest observed include the PdIV complex [PdBn5 ]- , which did not fragment
      via a reductive elimination but lost BnH instead.

PMID- 27717039
TI  - Effects of Ethanol on Cellular Composition and Network Excitability of Human
      Pluripotent Stem Cell-Derived Neurons.
AB  - BACKGROUND: Prenatal alcohol exposure (PAE) in animal models results in
      excitatory-inhibitory (E/I) imbalance in neocortex due to alterations in the
      GABAergic interneuron (IN) differentiation and migration. Thus, E/I imbalance is
      a potential cause for intellectual disability in individuals with fetal alcohol
      spectrum disorder (FASD), but whether ethanol (EtOH) changes glutamatergic and
      GABAergic IN specification during human development remains unknown. Here, we
      created a human cellular model of PAE/FASD and tested the hypothesis that EtOH
      exposure during differentiation of human pluripotent stem cell-derived neurons
      (hPSNs) would cause the aberrant production of glutamatergic and GABAergic
      neurons, resulting in E/I imbalance. METHODS: We applied 50 mM EtOH daily to
      differentiating hPSNs for 50 days to model chronic first-trimester exposure. We
      used quantitative polymerase chain reaction, immunocytochemical, and
      electrophysiological analysis to examine the effects of EtOH on hPSN
      specification and functional E/I balance. RESULTS: We found that EtOH did not
      alter neural induction nor general forebrain patterning and had no effect on the
      expression of markers of excitatory cortical pyramidal neurons. In contrast, our
      data revealed highly significant changes to levels of transcripts involved with
      IN precursor development (e.g., GSX2, DLX1/2/5/6, NR2F2) as well as mature IN
      specification (e.g., SST, NPY). Interestingly, EtOH did not affect the number of
      GABAergic neurons generated nor the frequency or amplitude of miniature
      excitatory and inhibitory postsynaptic currents. CONCLUSIONS: Similar to in vivo
      rodent studies, EtOH significantly and specifically altered the expression of
      genes involved with IN specification from hPSNs, but did not cause imbalances of
      synaptic excitation-inhibition. Thus, our findings corroborate previous studies
      pointing to aberrant neuronal differentiation as an underlying mechanism of
      intellectual disability in FASD. However, in contrast to rodent binge models, our
      chronic exposure model suggests possible compensatory mechanisms that may cause
      more subtle defects of network processing rather than gross alterations in total
      E/I balance.

PMID- 27717042
TI  - Effects of melatonin on severe crush spinal cord injury-induced reactive
      astrocyte and scar formation.
AB  - The present work aimed at analyzing the effects of melatonin on scar formation
      after spinal cord injury (SCI). Upregulation of reactive astrocyte under SCI
      pathological conditions has been presented in several studies. It has been proved
      that the crucial factor in triggering this upregulation is proinflammatory
      cytokines. Moreover, scar formation is an important barrier to axonal
      regeneration through the lesion area. Melatonin plays an important role in
      reducing inflammation, but its effects on scar formation in the injured spinal
      cord remain unknown. Hence, we used the model of severe crush injury in mice to
      investigate the effects of melatonin on scar formation. Mice were randomly
      separated into four groups; SCI, SCI+Melatonin 1 (single dose), SCI+Melatonin 14
      (14 daily doses), and control. Melatonin was administered by intraperitoneal
      injection (10 mg/kg) after injury. Immunohistochemical analysis, Western blot,
      and behavioral evaluation were used to explore the effects of melatonin after SCI
      for 14 days. The melatonin-treated mice presented higher expression of neuronal
      markers (P < 0.001). Remarkably, the inflammatory response appeared to be greatly
      reduced in the SCI+Melatonin 14 group (P < 0.001), which also displayed less scar
      formation (P < 0.05). These findings suggest that melatonin inhibits scar
      formation by acting on inflammatory cytokines after SCI. Overall, our results
      suggest that melatonin is a promising treatment strategy after SCI that deserves
      further investigation. (c) 2016 Wiley Periodicals, Inc.

PMID- 27717043
TI  - Microscopic DTI accurately identifies early glioma cell migration: correlation
      with multimodal imaging in a new glioma stem cell model.
AB  - Monitoring glioma cell infiltration in the brain is critical for diagnosis and
      therapy. Using a new glioma Glio6 mouse model derived from human stem cells we
      show how diffusion tensor imaging (DTI) may predict glioma cell
      migration/invasion. In vivo multiparametric MRI was performed at one, two and
      three months of Glio6 glioma growth (Glio6 (n = 6), sham (n = 3)). This
      longitudinal study reveals the existence of a time window to study glioma
      cell/migration/invasion selectively. Indeed, at two months only Glio6 cell
      invasion was detected, while tumor mass formation, edema, blood-brain barrier
      leakage and tumor angiogenesis were detected later, at three months. To robustly
      confirm the potential of DTI for detecting glioma cell migration/invasion, a
      microscopic 3D-DTI (80 MUm isotropic spatial resolution) technique was developed
      and applied to fixed mouse brains (Glio6 (n = 6), sham (n = 3)). DTI changes were
      predominant in the corpus callosum (CC), a known path of cell migration.
      Fractional anisotropy (FA) and perpendicular diffusivity (D? ) changes derived
      from ex vivo microscopic 3D-DTI were significant at two months of tumor growth.
      In the caudate putamen an FA increase of +38% (p < 0.001) was observed, while in
      the CC a - 28% decrease in FA (p < 0.005) and a + 95% increase in D? (p < 0.005)
      were observed. In the CC, DTI changes and fluorescent Glio6 cell density obtained
      by two-photon microscopy in the same brains were correlated (p < 0.001, r =
      0.69), validating FA and D? as early quantitative biomarkers to detect glioma
      cell migration/invasion. The origin of DTI changes was assessed by electron
      microscopy of the same tract, showing axon bundle disorganization. During the
      first two months, Glio6 cells display a migratory phenotype without being
      associated with the constitution of a brain tumor mass. This offers a unique
      opportunity to apply microscopic 3D-DTI and to validate DTI parameters FA and D?
      as biomarkers for glioma cell invasion.

PMID- 27717041
TI  - Effects of Gabra2 Point Mutations on Alcohol Intake: Increased Binge-Like and
      Blunted Chronic Drinking by Mice.
AB  - BACKGROUND: Alcohol use disorders are associated with single-nucleotide
      polymorphisms in GABRA2, the gene encoding the GABAA receptor alpha2-subunit in
      humans. Deficient GABAergic functioning is linked to impulse control disorders,
      intermittent explosive disorder, and to drug abuse and dependence, yet it remains
      unclear whether alpha2-containing GABAA receptor sensitivity to endogenous
      ligands is involved in excessive alcohol drinking. METHODS: Male wild-type (Wt)
      C57BL/6J and point-mutated mice rendered insensitive to GABAergic modulation by
      benzodiazepines (BZD; H101R), allopregnanolone (ALLO) or
      tetrahydrodeoxycorticosterone (THDOC; Q241M), or high concentrations of ethanol
      (EtOH) (S270H/L277A) at alpha2-containing GABAA receptors were assessed for their
      binge-like, moderate, or escalated chronic drinking using drinking in the dark,
      continuous access (CA) and intermittent access (IA) to alcohol protocols,
      respectively. Social approach by mutant and Wt mice in forced alcohol abstinence
      was compared to approach by EtOH-naive controls. Social deficits in forced
      abstinence were treated with allopregnanolone (0, 3.0, 10.0 mg/kg,
      intraperitoneal [i.p.]) or midazolam (0, 0.56, 1.0 mg/kg, i.p.). RESULTS: Mice
      with BZD-insensitive alpha2-containing GABAA receptors (H101R) escalated their
      binge-like drinking. Mutants harboring the Q241M point substitution in Gabra2
      showed blunted chronic intake in the CA and IA protocols. S270H/L277A mutants
      consumed excessive amounts of alcohol but, unlike wild-types, they did not show
      forced abstinence-induced social deficits. CONCLUSIONS: These findings suggest a
      role for: (i) H101 in species-typical binge-like drinking, (ii) Q241 in escalated
      chronic drinking, and (iii) S270 and/or L277 in the development of forced
      abstinence-associated social deficits. Clinical findings report reduced BZD
      binding sites in the cortex of dependent patients; the present findings suggest a
      specific role for BZD-sensitive alpha2-containing receptors. In addition, amino
      acid residue 241 in Gabra2 is necessary for positive modulation and activation of
      GABAA receptors by ALLO and THDOC; we postulate that neurosteroid action on
      alpha2-containing receptor may be necessary for escalated chronic EtOH intake.

PMID- 27717045
TI  - Rim, Side Arms, and Cavity: Three Sites for the Recognition of Anions by
      Tetraazolium Resorcinarene Cavitands.
AB  - Two tetrabenzoimidazolium-resorcinarene cavitands were prepared and used for the
      recognition of chloride, bromide, iodide, cyanide, nitrate, perchlorate,
      hexanoate, benzenesulfonate, and p-toluenesulfonate. Binding affinities of the
      two cavitands were determined by 1 H NMR titration and computational analysis.
      The observed spectral changes were related to specific interaction sites, which
      were supported by the computational studies. In the case of the C2-H
      tetrabenzoimidazolium-resorcinarene, the recognition region of the inorganic
      anions and hexanoate was located at the rim of the cavitand, although chloride
      and bromide also interacted with the aromatic C-H bonds located between adjacent
      arms of the cavitand. By contrast, the recognition of the two anions with an
      aromatic ring (benzenesulfonate and p-toluenesulfonate) results from
      encapsulation of the aromatic part of the anions inside the hydrophobic cavity of
      the host. In the case of the C2-Me tetrabenzoimizazolium-resorcinarene receptor,
      the ability of the molecule to bind all inorganic anions and hexanoate was
      suppressed, but the receptor maintained its ability to strongly bind
      benzenesulfonate and p-toluenesulfonate. This is interpreted in terms of
      suppression of the ability of the cavitand to form hydrogen bonds at the rim of
      the molecule due to replacement of the C2-H proton by a methyl group, while the
      hydrophobic pocket of the molecule maintains its binding abilities.

PMID- 27717046
TI  - Superabsorbent, High Porosity, PAMPS-Based Hydrogels through Emulsion Templating.
AB  - Swell! Superabsorbent, mechanically robust, high-porosity hydrogels based on
      poly(2-acrylamido-2-methyl-1-propanesulfonic acid) have been successfully
      synthesized by templating within high internal phase emulsions (HIPEs). These
      hydrogel polyHIPEs (HG-PHs) exhibit unusually high uptakes of water and of
      artificial urine through structure- and crosslinking-dependent hydrogel-swelling
      driven void expansion. An HG-PH with 3.1 mmol g-1 of highly accessible sulfonic
      acid groups exhibits a 7 meq NaOH ion exchange capacity per gram polymer and
      rapid dye absorption. The highly swollen HG-PHs do not fail at compressive
      strains of up to 60%, they retain water and recover their shapes upon the removal
      of stress. Unusually, the dry hydrogels have relatively high compressive moduli
      and achieve relatively high stresses at 70% strain.

PMID- 27717044
TI  - Synthesis of Potent and Selective HDAC6 Inhibitors Bearing a Cyclohexane- or
      Cycloheptane-Annulated 1,5-Benzothiazepine Scaffold.
AB  - Selective inhibitors of histone deacetylase 6 (HDAC6) are an emerging class of
      pharmaceuticals due to the involvement of HDAC6 in different pathways related to
      neurodegenerative diseases, cancer, and immunology. Herein, the synthesis of ten
      new benzohydroxamic acids, constructed by employing the tetrahydrobenzothiazepine
      core as a privileged pharmacophoric unit, is described. This is the first report
      on the synthesis and isolation of octahydrodibenzothiazepines and octahydro-6H
      benzocycloheptathiazepines, which were then used to develop a new class of HDAC6
      inhibitors. Evaluations of their HDAC-inhibiting activity resulted in the
      identification of cis-N-(4-hydroxycarbamoylbenzyl)-1,2,3,4,4a,5,11,11a
      octahydrodibenzo[b,e][1,4]thiazepine-10,10-dioxide and cis-N-(4
      hydroxycarbamoylbenzyl)-7-trifluoromethyl-1,2,3,4,4a,5,11,11a
      octahydrodibenzo[b,e][1,4]thiazepine-10,10-dioxide as highly potent and selective
      HDAC6 inhibitors with activity in the low nanomolar range, which also show
      excellent selectivity on the enzymatic and cellular levels. Furthermore, four
      promising inhibitors were subjected to an Ames fluctuation assay, which revealed
      no mutagenic effects associated with these structures.

PMID- 27717047
TI  - Activation of Aromatic C-C Bonds of 2,2'-Bipyridine Ligands.
AB  - 4,4'-Disubstituted-2,2'-bipyridine ligands coordinated to MoII and ReI cationic
      fragments become dearomatized by an intramolecular nucleophilic attack from a
      deprotonated N-alkylimidazole ligand in cis disposition. The subsequent
      protonation of these neutral complexes takes place on a pyridine carbon atom
      rather than at nitrogen, weakening an aromatic C-C bond and affording a
      dihydropyridyl moiety. Computational calculations allowed for the rationalization
      of the formation of the experimentally obtained products over other plausible
      alternatives.

PMID- 27717048
TI  - Ternary Organic Solar Cells Based on Two Compatible Nonfullerene Acceptors with
      Power Conversion Efficiency >10.
AB  - Two different nonfullerene acceptors and one copolymer are used to fabricate
      ternary organic solar cells (OSCs). The two acceptors show unique interactions
      that reduce crystallinity and form a homogeneous mixed phase in the blend film,
      leading to a high efficiency of ~10.3%, the highest performance reported for
      nonfullerene ternary blends. This work provides a new approach to fabricate high
      performance OSCs.

PMID- 27717049
TI  - Enantio- and Stereoselective Cyclopolymerization of Hexa-1,5-diene Catalyzed by
      Zirconium Complexes Possessing Optically Active Bis(phenolato) Ligands.
AB  - Enantio- and stereoselective cyclopolymerization of hexa-1,5-diene was achieved
      by enantiomerically pure dichloro zirconium(IV) pre-catalysts 2 possessing chiral
      [OSSO]-type bis(phenolate) ligands (-)-1 and (+)-1 in combination with dried
      methylaluminoxane (dMAO) as an activator. The corresponding activities were
      recorded with quite high values up to 1,960 g mmol(2)-1 h-1 , which are extremely
      larger than those of the related complexes. The microstructure analysis for the
      PMCPs furnished by pre-catalysts (Lambda,S,S)-2 and (Delta,R,R)-2 showed good
      isotacticity factors (alpha = 75-78%) and relatively high proportions of trans
      cyclopentane rings (sigma = 14-21%). These enantiomeric PMCPs exhibited large
      specific optical rotations ([alpha]D = +28 to +32 degrees  from (Lambda,S,S)-2, 
      26 to -34 degrees  from (Delta,R,R)-2).

PMID- 27717050
TI  - Transient and persistent behavioral and molecular changes in primiparous female
      Wistar rats.
AB  - Motherhood brings about a multitude of behavioral and physiological changes in
      dams and some of these persist until after weaning. We studied behavioral changes
      associated with reproductive experience at lactating day (LD)8, at weaning
      (LD21), and 28 days post-weaning (PW28) compared to nulliparous (NP) females.
      Furthermore, in another cohort of animals, we quantified mRNA expression of five
      target genes known to be associated with maternal experience: arginin
      vasopressin(Avp) and its 1A receptor(Avpr1a), oxytocin(Oxt) and its
      receptor(Oxtr), and corticotropin-releasing hormone(Crh) in three key maternal
      region: the medial preoptic area (MPOA), bed nucleus of the stria terminalis
      (BNST) and paraventricular hypothalamic nucleus(PVN). Although dams were slightly
      less anxious than NP at LD8, this effect did not persist at LD21 and PW28. No
      differences in social preference were found between the four groups. In the
      maternal responsiveness test (MRT), LD8 and LD21 dams were immediately responsive
      to pups whereas NP largely avoided the pups throughout 12-day period. PW28
      females were significantly more responsive to pups than NP females, but less than
      LD8 and LD21 females. The mRNA expression of Avp in the PVN, Avpr1a in the BNST
      and Oxtr in the MPOA and BNST was increased, whereas mRNA expression of Avpr1a
      was reduced in the PVN, at LD8 compared to NP. Although Oxtr in the BNST and Avp
      in the PVN were still somewhat (non-significantly) increased at LD21, all levels
      of gene expression had normalized at PW28. Our results emphasize the transient
      nature of these behavioral and molecular adaptations, except for a persistent up
      regulation of maternal responsiveness.

PMID- 27717051
TI  - The Evolution of the Total Synthesis of Rocaglamide.
AB  - The complex flavagline, (-)-rocaglamide, possesses a synthetically intriguing
      tricyclic scaffold with five contiguous stereocenters and also exhibits potent
      anticancer, anti-inflammatory and insecticidal activity. This full account
      details distinct approaches to (+/-)- and (-)-rocaglamide utilizing Bronsted acid
      catalyzed and asymmetric Pd0 -catalyzed Nazarov chemistry developed in our
      laboratory, respectively. The successful asymmetric synthesis revealed unforeseen
      mechanistic complexity that required adjusting our strategy to overcome an
      unanticipated racemization process, an unusual reversible ring-cleavage step and
      a very facile trialkylsilyl group migration.

PMID- 27717052
TI  - Integration of Organic Electrochemical and Field-Effect Transistors for
      Ultraflexible, High Temporal Resolution Electrophysiology Arrays.
AB  - Integration of organic electrochemical transistors and organic field-effect
      transistors is successfully realized on a 600 nm thick parylene film toward an
      electrophysiology array. A single cell of an integrated device and a 2 * 2
      electrophysiology array succeed in detecting electromyogram with local
      stimulation of the motor nerve bundle of a transgenic rat by a laser pulse.

PMID- 27717053
TI  - Coupling of D2R Short but not D2R Long receptor isoform to the Rho/ROCK signaling
      pathway renders striatal neurons vulnerable to mutant huntingtin.
AB  - Huntington's disease, an inherited neurodegenerative disorder, results from
      abnormal polyglutamine extension in the N-terminal region of the huntingtin
      protein. This mutation causes preferential degeneration of striatal projection
      neurons. We previously demonstrated, in vitro, that dopaminergic D2 receptor
      stimulation acted in synergy with expanded huntingtin to increase aggregates
      formation and striatal death through activation of the Rho/ROCK signaling
      pathway. In vivo, in a lentiviral-mediated model of expanded huntingtin
      expression in the rat striatum, we found that the D2 antagonist haloperidol
      protects striatal neurons against expanded huntingtin-mediated toxicity. Two
      variant transcripts are generated by alternative splicing of the of D2 receptor
      gene, the D2R-Long and the D2R-Short, which are thought to play different
      functional roles. We show herein that overexpression of D2R-Short, but not D2R
      Long in cell lines is associated with activation of the RhoA/ROCK signaling
      pathway. In striatal neurons in culture, the selective D2 agonist Quinpirole
      triggers phosphorylation of cofilin, a downstream effector of ROCK, which is
      abrogated by siRNAs that knockdown both D2R-Long and D2R-Short, but not by siRNAs
      targeting D2R-Long alone. Aggregate formation and neuronal death induced by
      expanded huntingtin, were potentiated by Quinpirole. This D2 agonist-mediated
      effect was selectively inhibited by the siRNA targeting both D2R-Long and D2R
      Short but not D2R-Long alone. Our data provide evidence for a specific coupling
      of D2R-Short to the RhoA/ROCK/cofilin pathway, and its involvement in striatal
      vulnerability to expanded huntingtin. A new route for targeting Rho-ROCK
      signaling in Huntington's disease is unraveled with our findings.

PMID- 27717055
TI  - Polymer Capsules for Plaque-Targeted In Vivo Delivery.

PMID- 27717054
TI  - Alpha-power modulation reflects the balancing of task requirements in a selective
      attention task.
AB  - Recent research has related the orienting of selective attention to the
      lateralization of posterior EEG alpha power (~8 to 12 Hz). Typically, alpha power
      decreases over the side of the head contralateral to the cued side of space.
      However, it is not clear how this lateralization affects behavior. We recorded
      EEG from 20 participants while they performed a cued visual discrimination task
      under three different response-deadline conditions to investigate the effect of
      alpha-power modulation on behavioral performance in more detail. Although all
      participants benefited from the cue behaviorally and adjusted their performance
      according to the response deadlines, we found the cue-related alpha-power
      modulation to depend on the general alpha-power level at baseline: Only
      participants with high baseline alpha power showed significant cue-related alpha
      power lateralization that was, however, strikingly similar across response
      deadline conditions. On the other hand, participants with low alpha power at
      baseline did not show any lateralization, but adjusted their alpha levels
      according to the response-deadline instructions and, more importantly, showed a
      stronger influence of the task instructions on behavioral performance and adapted
      their response accuracies to the task requirements more flexibly. These findings
      challenge the often-assumed role of alpha-power lateralization for attentional
      deployment. While alpha power seems to be related to behavioral performance and
      the orienting of attention, this relationship is rather complex and, at least
      under the current task requirements, the general alpha-power state seems to be
      more strongly related to behavioral performance (in our case, the flexible
      adjustment to task requirements) than the cue-related lateralization.

PMID- 27717056
TI  - Functionalization of Planet-Satellite Nanostructures Revealed by Nanoscopic
      Localization of Distinct Macromolecular Species.
AB  - The development of a straightforward method is reported to form hybrid
      polymer/gold planet-satellite nanostructures (PlSNs) with functional polymer.
      Polyacrylate type polymer with benzyl chloride in its backbone as a
      macromolecular tracer is synthesized to study its localization within PlSNs by
      analyzing the elemental distribution of chlorine. The functionalized nanohybrid
      structures are analyzed by scanning transmission electron microscopy, electron
      energy loss spectroscopy, and spectrum imaging. The results show that the RAFT
      (reversible addition-fragmentation chain transfer) polymers' sulfur containing
      end groups are colocalized at the gold cores, both within nanohybrids of simple
      core-shell morphology and within higher order PlSNs, providing microscopic
      evidence for the affinity of the RAFT group toward gold surfaces.

PMID- 27717057
TI  - Open access follow-up care for early breast cancer: a randomised controlled
      quality of life analysis.
AB  - This study evaluated the acceptability of a supportive model of follow-up. One
      hundred and twelve women recovering from breast cancer were randomised to receive
      standard breast clinic aftercare (Control n = 56) or on demand by open access
      aftercare by breast care nurses (Intervention n = 56). Participants attended a
      support-based psycho-educational programme delivered in four half-day group
      sessions. Three quality of life questionnaires (EORTC QLQ-C30, QLQ-BR23, HADS)
      were administered at baseline and 6-monthly intervals for 2 years. Multilevel
      linear regression modelling methods were used for evaluation. Age was found to be
      a statistically significant predictor of quality of life in several sub-scales.
      Increasing age was negatively associated with sexual functioning, systematic
      therapy side effects and physical functioning, and positively associated with
      future perspective. Aftercare assignment was not found to be a statistically
      significant predictor. Women treated for early breast cancer were not
      disadvantaged by allocation to the open access supportive care model in terms of
      quality of life experienced. The model for follow-up was demonstrated to be a
      feasible alternative to routinised hospital-based follow-up and adds to the
      evidence for stratified follow-up for low-risk cancer patients, incorporating
      self-management education. Stratified follow-up pathways are viewed as a
      preferable approach.

PMID- 27717058
TI  - Pro-Life Arguments Against Infanticide and Why they are Not Convincing.
AB  - Alberto Giubilini and Francesca Minerva's controversial article 'After-Birth
      Abortion: Why Should the Baby Live?' has received a lot of criticism since its
      publishing. Part of the recent criticism has been made by pro-life philosopher
      Christopher Kaczor, who argues against infanticide in his updated book 'Ethics of
      Abortion'. Kaczor makes four arguments to show where Giubilini and Minerva's
      argument for permitting infanticide goes wrong. In this article I argue that
      Kaczor's arguments, and some similar arguments presented by other philosophers,
      are mistaken and cannot show Giubilini and Minerva's view to be flawed. I claim
      that if one wants to reject the permissibility of infanticide, one must find
      better arguments for doing so.

PMID- 27717059
TI  - Human COL5A1 polymorphisms and quadriceps muscle-tendon mechanical stiffness in
      vivo.
AB  - NEW FINDINGS: What is the central question of the study? Do COL5A1 gene variants,
      previously reported to have diminished transcript stability, manifest in
      physiological phenotypes of quadriceps muscle-tendon contractile properties and
      mechanical stiffness in humans? What is the main finding and its importance?
      COL5A1 gene variants influence mechanical stiffness, not seeming to affect low
      level contractile properties in humans. Functional differences in COL5A1 manifest
      during moderate- to high-level contractions. Polymorphisms of the collagen type V
      alpha 1 chain (COL5A1) gene are purported to influence mechanical properties of
      collagenous tissues. Our purpose was to assess musculotendinous contractile
      properties of the quadriceps in relationship to the genetic influence of
      mechanical stiffness. Eighty recreationally active males (aged 19-31 years) were
      assessed for the presence of three genetic polymorphisms associated with COL5A1
      mRNA stability (rs4919510, rs1536482 and rs12722). Genotypes were determined
      using real-time PCR. Stiffness and contractile properties of the knee
      musculotendinous complex were assessed by maximal isometric voluntary
      contractions, ramp isometric voluntary contractions, electrically stimulated
      contractile events and ultrasonography. All genotype groups were able to activate
      their knee extensors fully (>97%) as assessed by the interpolated twitch
      technique and presented no differences in muscle-tendon contractile properties at
      low submaximal contraction intensities. For the quadriceps muscle-tendon at
      moderate ramp contractions of 50 and 60% maximal voluntary contraction, the
      rs12722 CT and TT genotypes had ~30% greater mean stiffness. The rs1536482 AG and
      GG genotypes showed a similar trend, but did not achieve statistical
      significance. Variants of the COL5A1 gene seem to influence quadriceps muscle
      tendon stiffness but do not affect low-level contractile properties.

PMID- 27717060
TI  - Ultrafast Preparation of AIE-Active Fluorescent Organic Nanoparticles via a "One
      Pot" Microwave-Assisted Kabachnik-Fields Reaction.
AB  - The development of effective strategies for fabrication of fluorescent organic
      nanoparticles (FONs) with an aggregation-induced emission (AIE) feature has an
      important impact on the biomedical applications of these AIE-active FONs. In the
      current work, an ultrafast strategy for fabricating AIE-active FONs is developed
      through a "one-pot" microwave-assisted, catalysts-free, and solvent-free
      Kabachnik-Fields (KF) reaction for the first time. It is demonstrated that such
      organophosphorous-containing AIE-active block polymers can be synthesized within
      2 min under air atmosphere through the microwave-assisted KF reaction. These
      polymers show amphiphilic properties and can self-assemble into mPEG-CHO-Phe-NH2 
      DEP FONs, which display high water dispersibility and desirable optical
      properties. Biological evaluation results suggest that the mPEG-CHO-Phe-NH2 -DEP
      FONs exhibit low toxicity and are potential for biological imaging applications.
      More importantly, many other multifunctional AIE-active FONs can also be
      fabricated through the strategy described in this work owing to the universality
      of KF reaction. Besides, combined with the excellent properties of mPEG-CHO-Phe
      NH2 -DEP FONs, it is believed that such microwave-assisted KF reaction shall be
      an effective route for designing various AIE-active nanomaterials for different
      biomedical applications.

PMID- 27717061
TI  - A qualitative study of advanced nurse practitioners' use of physical assessment
      skills in the community: shifting skills across professional boundaries.
AB  - AIMS AND OBJECTIVES: To explore multiple perspectives on the use of physical
      assessment skills by advanced nurse practitioners in the UK. BACKGROUND: Physical
      assessment skills practices are embedded in advanced nursing practice roles in
      the UK. There is little evidence on how these skills are used by advanced nurse
      practitioners in the community. DESIGN: Case study. METHODS: A qualitative
      interpretative single-embedded case study of 22 participants from South of
      England. A framework method analysed interview data collected by the researcher
      between March-August 2013. Participants included nurses, doctors, nurse educators
      and managers. FINDINGS: Physical assessment skills education at universities is
      part of a policy shift to develop a flexible workforce in the UK. Shared physical
      assessment practices are less to do with role substitution and more about
      preparing practitioners with skills that are fit for purpose. Competence,
      capability and performance with physical assessment skills are an expectation of
      advanced nursing practice. CONCLUSIONS: These skills are used successfully by
      community advanced nurse practitioners to deliver a wide range of services in
      response to changing patient need. The introduction of physical assessment skills
      education to undergraduate professional preparation would create a firm
      foundation to develop these skills in postgraduate education. RELEVANCE TO
      CLINICAL PRACTICE: Physical assessment education prepares nurses with the
      clinical competencies to carry out healthcare reforms in the UK. Shared sets of
      clinical assessment competencies between disciplines have better outcomes for
      patients. Levels of assessment competence can depend on the professional
      attributes of individual practitioners. Unsupportive learning cultures can hinder
      professional development of advanced nursing practice.

PMID- 27717062
TI  - Body Dysmorphic Disorder: Contraindication or Ethical Justification for Female
      Genital Cosmetic Surgery in Adolescents.
AB  - Is Female Genital Cosmetic Surgery for an adolescent with Body Dysmorphic
      Disorder ever ethically justified? Cosmetic genital surgery (specifically
      labioplasty) for adolescent girls is one of the most ethically controversial
      forms of cosmetic surgery and Body Dysmorphic Disorder is typically seen as a
      contraindication for cosmetic surgery. Two key ethical concerns are (1) that Body
      Dysmorphic Disorder undermines whatever capacity for autonomy the adolescent has;
      and (2) even if there is valid parental consent, the presence of Body Dysmorphic
      Disorder means that cosmetic surgery will fail in its aims. In this article, we
      challenge, in an evidence-based way, the standard view that Body Dysmorphic
      Disorder is a contraindication for genital cosmetic surgery in adolescents. Our
      argument gathers together and unifies a substantial amount of disparate research
      in the context of an ethical argument. We focus on empirical questions about
      benefit and harm, because these are ethically significant. Answers to these
      questions affect the answer to the ethical question. We question the claim that
      there would be no benefit from surgery in this situation, and we consider
      possible harms that might be done if treatment is refused. For an adolescent with
      Body Dysmorphic Disorder, the most important thing may be to avoid harm. We find
      ourselves arguing for the ethical justifiability of cosmetic labioplasty for an
      adolescent with Body Dysmorphic Disorder, even though we recognize that it is a
      counter intuitive position. We explain how we reached our conclusion.

PMID- 27717064
TI  - High-order motor cortex in rats receives somatosensory inputs from the primary
      motor cortex via cortico-cortical pathways.
AB  - The motor cortex of rats contains two forelimb motor areas; the caudal forelimb
      area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to
      correspond to the premotor and/or supplementary motor cortices of primates, which
      are higher-order motor areas that receive somatosensory inputs, it is unknown
      whether the RFA of rats receives somatosensory inputs in the same manner. To
      investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess
      the motor cortex in rats following a brief electrical stimulation of the
      forelimb. This procedure was followed by intracortical microstimulation (ICMS)
      mapping to identify the motor representations in the imaged cortex. The combined
      use of VSD imaging and ICMS revealed that both the CFA and RFA received
      excitatory synaptic inputs after forelimb stimulation. Further evaluation of the
      sensory input pathway to the RFA revealed that the forelimb-evoked RFA response
      was abolished either by the pharmacological inactivation of the CFA or a cortical
      transection between the CFA and RFA. These results suggest that forelimb-related
      sensory inputs would be transmitted to the RFA from the CFA via the cortico
      cortical pathway. Thus, the present findings imply that sensory information
      processed in the RFA may be used for the generation of coordinated forelimb
      movements, which would be similar to the function of the higher-order motor
      cortex in primates.

PMID- 27717065
TI  - Sediment ecotoxicology-Current research on laboratory methods: An introduction.

PMID- 27717066
TI  - The authors' reply.

PMID- 27717063
TI  - Structure of the SLC4 transporter Bor1p in an inward-facing conformation.
AB  - Bor1p is a secondary transporter in yeast that is responsible for boron
      transport. Bor1p belongs to the SLC4 family which controls bicarbonate exchange
      and pH regulation in animals as well as borate uptake in plants. The SLC4 family
      is more distantly related to members of the Amino acid-Polyamine-organoCation
      (APC) superfamily, which includes well studied transporters such as LeuT, Mhp1,
      AdiC, vSGLT, UraA, SLC26Dg. Their mechanism generally involves relative movements
      of two domains: a core domain that binds substrate and a gate domain that in many
      cases mediates dimerization. To shed light on conformational changes governing
      transport by the SLC4 family, we grew helical membrane crystals of Bor1p from
      Saccharomyces mikatae and determined a structure at ~6 A resolution using cryo
      electron microscopy. To evaluate the conformation of Bor1p in these crystals, a
      homology model was built based on the related anion exchanger from red blood
      cells (AE1). This homology model was fitted to the cryo-EM density map using the
      Molecular Dynamics (MD) Flexible Fitting method and then relaxed by all-atom MD
      simulation in explicit solvent and membrane. Mapping of water accessibility
      indicates that the resulting structure represents an inward-facing conformation.
      Comparisons of the resulting Bor1p model with the X-ray structure of AE1 in an
      outward-facing conformation, together with MD simulations of inward-facing and
      outward-facing Bor1p models, suggest rigid body movements of the core domain
      relative to the gate domain. These movements are consistent with the rocking
      bundle transport mechanism described for other members of the APC superfamily.

PMID- 27717067
TI  - One health-Transdisciplinary opportunities for SETAC leadership in integrating
      and improving the health of people, animals, and the environment.
AB  - One Health is a collaborative, transdisciplinary effort working locally,
      nationally, and globally to improve health for people, animals, plants, and the
      environment. The term is relatively new (from ~2003), and it is increasingly
      common to see One Health included by name in interinstitutional research
      partnerships, conferences, communications, and organizational frameworks,
      particularly those championed by the human health and veterinary medical
      communities. Environmental quality is arguably the least developed component
      within the One Health framework, but can be guided by expertise within the
      Society of Environmental Toxicology and Chemistry (SETAC). Despite SETAC's long
      history of tripartite (academic, government, business) interdisciplinary
      environmental science activities, the term "One Health" is seldom used in SETAC
      communications (i.e., many of SETAC's activities are guided by One Health, but it
      is called by other names in SETAC's journals, newsletters, and presentations).
      Accordingly, the objective of this Focus article is to introduce the One Health
      concept to the SETAC membership. The article discusses the origins, evolution,
      and utility of the One Health approach as an organizational framework and
      provides key examples of ways in which SETAC expertise can benefit the One Health
      community. The authors assert that One Health needs SETAC and, to be most
      effective, SETAC needs One Health. Given that One Health to date has focused too
      little on the environment, on ecosystems, and on contaminants, SETAC's
      constructive involvement in One Health presents an opportunity to accelerate
      actions that will ultimately better protect human and ecosystem health. Environ
      Toxicol Chem 2016;35:2383-2391. (c) 2016 SETAC.

PMID- 27717068
TI  - To the editor.

PMID- 27717069
TI  - Carbon and nitrogen stable isotopic offsets between diet and hair/feces in
      captive chimpanzees.
AB  - RATIONALE: Estimation of the stable isotopic offsets between tissue and diet is
      important for dietary reconstructions. Although stable isotopic studies of
      chimpanzees (Pan troglodytes) are increasing, the isotopic offsets in chimpanzees
      have never been studied. In this study, the carbon and nitrogen stable isotopic
      offset values in hair and feces were measured for 13 captive chimpanzees for the
      first time. METHODS: All consumed food items and quantities were recorded for
      each individual for 1 week. Food samples were typically collected three times,
      hair was collected 3 weeks after the experimental week, and feces were collected
      ad libitum during the experimental week. The stable carbon and nitrogen isotope
      ratios were measured using elemental analyzer-isotope ratio mass spectrometry (EA
      IRMS). RESULTS: As the results of Monte Carlo analysis, the estimated carbon and
      nitrogen offsets between the hair and diet were +3.0 to +3.90/00 and +2.8 to
      +3.70/00, respectively, for the 95% confidence intervals (CIs). The 95% CIs of
      the carbon and nitrogen offset values between the feces and diet were -1.6 to
      0.00/00 and +1.2 to +2.70/00, respectively. CONCLUSIONS: These offset values are
      generally consistent with those of the other primate species reported in previous
      studies. However, potential variations in the offset values due to dietary and
      physiological factors should be studied in detail in the future. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27717070
TI  - Guided Folding of Nematic Liquid Crystal Elastomer Sheets into 3D via Patterned
      1D Microchannels.
AB  - Two-dimensional liquid-crystal elastomer (LCE) sheets with preprogrammed
      topological defects are prepared by aligning liquid-crystal monomers within
      micropatterned epoxy channels, followed by photopolymerization. Upon heating, the
      LCE films form various three-dimensional structures in agreement with theoretical
      design. The miniaturized LCE actuators offer large-area work capacities (~1.05 J
      m-2 ) to lift over 700 times their own weight.

PMID- 27717071
TI  - A Stretchable Multicolor Display and Touch Interface Using Photopatterning and
      Transfer Printing.
AB  - An intrinsically soft and stretchable multicolor display and touch interface is
      reported. Red, green, and blue pixels are formed separately by photopatterning
      transition-metal-doped ZnS embedded in silicone gels and transfer printing onto
      an elastomeric dielectric sheet. The device shows stable illumination while being
      stretched up to 200% area strain or under different deformation modalities. It
      also introduces capabilities for dynamic colorations and multipoint capacitive
      touch sensing.

PMID- 27717072
TI  - An Elastic, Conductive, Electroactive Nanocomposite Binder for Flexible Sulfur
      Cathodes in Lithium-Sulfur Batteries.
AB  - A conductive, elastic, electroactive binder composed of polypyrrole and
      polyurethane is adopted for flexible, high-loading lithium-sulfur cathodes. The
      conductivity of the polypyrrole helps mitigate the negative effects of insulating
      sulfur, and the elastomeric matrix accommodates sulfur volume expansion. The
      binder is used with a simple carbon/sulfur composite to produce high-performance,
      flexible electrodes without excessive carbon, interlayers, or special additives.

PMID- 27717073
TI  - Migration and nutritional status of Tarahumara schoolchildren from Chihuahua
      State (Mexico).
AB  - OBJECTIVE: The Tarahumara ethnic group is composed of indigenous people from the
      Sierra Madre Occidental of Mexico. Conditions of isolation and poverty compel
      them to migrate to the city in search of better opportunities. This work aims to
      explore the influence of migration on the growth and nutritional status of
      Tarahumara schoolchildren. METHODS: One hundred Tarahumara students were analyzed
      (50 rural with a mean age of 9.78 +/- 1.25 years; 50 urban aged 10.0 +/- 1.04
      years), comparing anthropometric indicators and body composition (T-Student, U
      Mann-Whitney Tests). RESULTS: Twenty percent of rural girls and 35% of rural boys
      showed stunted growth compared to only 9% of the urban girls (no stunted growth
      among urban boys). Migrants showed greater body size, skinfold thickness, and fat
      percentage. Weight excess, understood as an increase in the prevalence of
      overweight and obesity, was detected in 17.8% of urban boys and 13.6% of urban
      girls compared to 10.0% of boys and 3.3% of girls of the rural series.
      CONCLUSION: Migration reduces stunting and increases adiposity.

PMID- 27717076
TI  - Liquid-Phase Separation Methods for Environmental Analysis.

PMID- 27717074
TI  - Different cardiometabolic effects of atorvastatin in men with normal vitamin D
      status and vitamin D insufficiency.
AB  - BACKGROUND: Vitamin D is suggested to reduce cardiovascular risk. HYPOTHESIS:
      Circulating levels of plasma lipids and other cardiovascular risk factors may
      differ between statin-treated patients with different vitamin D status. METHODS:
      We studied 3 age- and weight-matched groups of men with elevated low-density
      lipoprotein cholesterol (LDL-C) levels: vitamin D-naive men with vitamin D
      insufficiency (group A, n = 18), men with vitamin D deficiency/insufficiency
      effectively treated with vitamin D preparations (group B, n = 16), and vitamin D
      naive men with normal vitamin D status (group C, n = 16). All patients were then
      treated with atorvastatin (20 mg daily) for 4 months. Plasma lipids, glucose
      homeostasis markers, and plasma levels of uric acid, high-sensitivity C-reactive
      protein (hsCRP), homocysteine, and fibrinogen were assessed before and at the end
      of atorvastatin therapy. RESULTS: Study groups did not differ in baseline levels
      of plasma lipids. Men with vitamin D deficiency or insufficiency effectively
      treated with vitamin D preparations were characterized by decreased insulin
      sensitivity and higher circulating levels of hsCRP, homocysteine, and fibrinogen
      in comparison with the remaining groups of patients. Although atorvastatin
      decreased plasma levels of total cholesterol and LDL-C to a similar extent in all
      study groups, its effect on uric acid, hsCRP, homocysteine, and fibrinogen was
      more pronounced in patients from groups B and C than in men from group A.
      Moreover, in patients with vitamin D insufficiency, atorvastatin impaired insulin
      sensitivity. CONCLUSIONS: The obtained results indicate that the strength of
      pleiotropic effects of atorvastatin depends on vitamin D status.

PMID- 27717078
TI  - Acute effects of resistance exercise on affect, arousal, and urge to drink in
      temporarily abstinent young adult hazardous drinkers.
AB  - BACKGROUND AND OBJECTIVE: Young adults frequently engage in hazardous alcohol
      consumption, and many meet the diagnostic criteria for an alcohol use disorder.
      The urge to drink is a defining symptom of alcohol dependence, and it is closely
      tied to and exacerbated by negative affect. This study examined the acute effect
      of resistance exercise on affect, arousal, and drinking urges in young adult
      (ages 21-40) hazardous drinkers. METHODS: On two separate occasions, 14
      participants underwent an 18-hour alcohol abstinence before completing, in a
      counter-balanced manner, a 20-minute session of resistance exercise and a 20
      minute video control. RESULTS: Significant improvements in affect (t = 2.07, p =
      .04) and arousal (t = 4.09, p < .01), but not urge to drink, were found with
      exercise. CONCLUSION: Single sessions of resistance exercise can positively alter
      affect and arousal during alcohol abstinence. SCIENTIFIC SIGNIFICANCE: Practical
      exercise interventions designed to alter affect and arousal could potentially
      alter drinking. (Am J Addict 2016;25:623-627).

PMID- 27717077
TI  - Semiconductor Photonic Nanocavity on a Paper Substrate.
AB  - Direct integration of semiconductor photonic nanocavities with paper substrates
      is demonstrated for the first time. 1D photonic crystal nanocavities successfully
      show lasing action on paper substrates. The device has great synergy as a sensor
      because paper has good wicking ability while a photonic crystal cavity has high
      figure of merit. The research provides a platform for eco-friendly and
      sustainable devices.

PMID- 27717079
TI  - Visible-Light-Promoted Metal-Free Aerobic Oxidation of Primary Amines to Acids
      and Lactones.
AB  - A unique metal-free aerobic oxidation of primary amines via visible light
      photocatalytic double carbon-carbon bonds cleavage and multi carbon-hydrogen
      bonds oxidation was observed. Aerobic oxidation of primary amines could be
      controlled to afford acids by using dioxane with 18 W CFL, and lactones by using
      DMF with 8 W green LEDs, respectively. A plausible mechanism was proposed based
      on control experiments. This observation showed direct evidences for the
      fragmentation in the aerobic oxidation of aliphatic primary amines.

PMID- 27717080
TI  - An illustrated comparison of processing methods for phase MRI and QSM: removal of
      background field contributions from sources outside the region of interest.
AB  - The elimination of so-called background fields is an essential step in phase MRI
      and quantitative susceptibility mapping (QSM). Background fields, which are
      caused by sources outside the region of interest (ROI), are often one to two
      orders of magnitude stronger than tissue-related field variations from within the
      ROI, hampering quantitative interpretation of field maps. This paper reviews the
      current literature on background elimination algorithms for QSM and provides
      insights into similarities and differences between the many algorithms proposed.
      We discuss the basic theoretical foundations and derive fundamental limitations
      of background field elimination. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27717081
TI  - Capture of 2D Microparticle Arrays via a UV-Triggered Thiol-yne "Click" Reaction.
AB  - Immobilization of colloidal assemblies onto solid supports via a fast UV
      triggered click-reaction is achieved. Transient assemblies of microparticles and
      colloidal materials can be captured and transferred to solid supports. The
      technique does not require complex reaction conditions, and is compatible with a
      variety of particle assembly methods.

PMID- 27717082
TI  - Stratification of unresponsive patients by an independently validated index of
      brain complexity.
AB  - OBJECTIVE: Validating objective, brain-based indices of consciousness in
      behaviorally unresponsive patients represents a challenge due to the
      impossibility of obtaining independent evidence through subjective reports. Here
      we address this problem by first validating a promising metric of consciousness
      the Perturbational Complexity Index (PCI)-in a benchmark population who could
      confirm the presence or absence of consciousness through subjective reports, and
      then applying the same index to patients with disorders of consciousness (DOCs).
      METHODS: The benchmark population encompassed 150 healthy controls and
      communicative brain-injured subjects in various states of conscious wakefulness,
      disconnected consciousness, and unconsciousness. Receiver operating
      characteristic curve analysis was performed to define an optimal cutoff for
      discriminating between the conscious and unconscious conditions. This cutoff was
      then applied to a cohort of noncommunicative DOC patients (38 in a minimally
      conscious state [MCS] and 43 in a vegetative state [VS]). RESULTS: We found an
      empirical cutoff that discriminated with 100% sensitivity and specificity between
      the conscious and the unconscious conditions in the benchmark population. This
      cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the
      identification of a number of unresponsive VS patients (9 of 43) with high values
      of PCI, overlapping with the distribution of the benchmark conscious condition.
      INTERPRETATION: Given its high sensitivity and specificity in the benchmark and
      MCS population, PCI offers a reliable, independently validated stratification of
      unresponsive patients that has important physiopathological and therapeutic
      implications. In particular, the high-PCI subgroup of VS patients may retain a
      capacity for consciousness that is not expressed in behavior. Ann Neurol
      2016;80:718-729.

PMID- 27717083
TI  - T-cell acute lymphoblastic leukemia in infants has distinct genetic and
      epigenetic features compared to childhood cases.
AB  - For reasons not yet understood, nearly all infants with acute lymphoblastic
      leukemia (ALL) are diagnosed with the B-cell type, with T-ALL in infancy
      representing a very rare exception. Clinical and molecular knowledge about infant
      T-ALL is still nearly completely lacking and it is also still unclear whether it
      represents a distinct disease compared to childhood T-ALL. To address this, we
      performed exome sequencing of three infant cases, which enabled the detection of
      mutations in NOTCH2, NOTCH3, PTEN, and KRAS. When analyzing the transcriptomes
      and miRNomes of the three infant and an additional six childhood T-ALL samples,
      we found 760 differentially expressed mRNAs and 58 differentially expressed
      miRNAs between these two cohorts. Correlation analysis for differentially
      expressed miRNA-mRNA target pairs revealed 47 miRNA-mRNA pairs, with many of them
      previously described to be aberrantly expressed in leukemia and cancer. Pathway
      analysis revealed differentially expressed pathways and upstream regulators
      related to the immune system or cancerogenesis such as the ERK5 pathway, which
      was activated in infant T-ALL. In summary, there are distinct molecular features
      in infant compared to childhood T-ALL on a transcriptomic and epigenetic level,
      which potentially have an impact on the development and course of the disease.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27717084
TI  - Effect of terpinyl acetate on the percutaneous absorption of caffeine in rats.

PMID- 27717085
TI  - Copper-Coated Liquid-Crystalline Elastomer via Bioinspired Polydopamine Adhesion
      and Electroless Deposition.
AB  - This study explores the functionalization of main-chain nematic elastomers with a
      conductive metallic surface layer using a polydopamine binder. Using a two-stage
      thiol-acrylate reaction, a programmed monodomain is achieved for thermoreversible
      actuation. A copper layer (~155 nm) is deposited onto polymer samples using
      electroless deposition while the samples are in their elongated nematic state.
      Samples undergo 42% contraction when heated above the isotropic transition
      temperature. During the thermal cycle, buckling of the copper layer is seen in
      the direction perpendicular to contraction; however, transverse cracking occurs
      due to the large Poisson effect experienced during actuation. As a result, the
      electrical conductivity of the layer reduced quickly as a function of thermal
      cycling. However, samples do not show signs of delamination after 25 thermal
      cycles. These results demonstrate the ability to explore multifunctional liquid
      crystalline composites using relatively facile synthesis, adhesion, and
      deposition techniques.

PMID- 27717086
TI  - Low-Temperature Transformation of Methane to Methanol on Pd1 O4 Single Sites
      Anchored on the Internal Surface of Microporous Silicate.
AB  - Direct conversion of methane to chemical feedstocks such as methanol under mild
      conditions is a challenging but ideal solution for utilization of methane. Pd1 O4
      single-sites anchored on the internal surface of micropores of a microporous
      silicate exhibit high selectivity and activity in transforming CH4 to CH3 OH at
      50-95  degrees C in aqueous phase through partial oxidation of CH4 with H2 O2 .
      The selectivity for methanol production remains at 86.4 %, while the activity for
      methanol production at 95  degrees C is about 2.78 molecules per Pd1 O4 site per
      second when 2.0 wt % CuO is used as a co-catalyst with the Pd1 O4 @ZSM-5.
      Thermodynamic calculations suggest that the reaction toward methanol production
      is highly favorable compared to formation of a byproduct, methyl peroxide.

PMID- 27717087
TI  - Depressive symptoms in patients with wounds: A cross-sectional study.
AB  - Depression slows wound healing in patients with chronic wounds. The prevalence of
      depressive symptoms differs in the literature and the current understandings of
      factors related to depression in patients with wounds have been limited. To
      investigate the prevalence of depressive symptoms and the associated factors in
      patients with wounds, we performed this retrospective study in which depressive
      symptoms were evaluated with the Patient Health Questionnaire 9-item (PHQ-9).
      Valid PHQ-9 scores were collected from 222 patients (112 males and 110 females;
      age: 64.1 +/- 15.8) out of 260 consecutive patients evaluated at an outpatient
      physical therapy wound clinic during 2012-2015. The proportion of patients with
      minimal to severe depressive symptoms was 81.5% [80.8% in patients with venous
      leg ulcers (VLUs) and 82.0% in non-VLUs]; 22.1% patients with wounds had scored
      positive for depression (moderate to severe depressive symptoms). Specific
      proportions of positive depression screening were 26.6% in patients with VLUs and
      18.8% in non-VLU patients, and 14.1 and 40.0% in patients with wounds <90 and >=
      90 days as of initial examination, respectively. PHQ-9 scores were significantly
      decreased from 5.85 +/- 6.01 at initial examination to 3.42 +/- 4.35 at last
      visit (p < 0.001). The odds of a positive depression screening was 3.20 (95% CI =
      [1.49, 6.87]) in patients with wounds >= 90 days (vs. < 90 days) and 2.53 (95% CI
      = [1.26, 5.08]) in patients with pain related to the wounds (vs. without pain),
      after patients' age, gender, and race were controlled for. No difference was
      found in proportions of positive depression screening between VLUs and other
      wound diagnoses. Depressive symptoms were common in patients with wounds,
      especially in patients with wounds >=90 days and with pain related to the wounds
      at initial examination. Therefore, clinicians should take into consideration
      patients' mental status upon management of wounds.

PMID- 27717089
TI  - Chromosomal microarray in a highly consanguineous population: diagnostic yield,
      utility of regions of homozygosity, and novel mutations.
AB  - Chromosomal microarray (CMA) has significantly improved diagnosing copy number
      variations (CNVs). Single nucleotide polymorphism (SNP) arrays confer additional
      utility in detecting regions of homozygosity (ROH). Investigating ROH for genes
      associated with recessive disorders for follow-up sequencing can aid in
      diagnosis. In this study, we performed a retrospective review of clinical and
      molecular data for 227 individuals from a highly consanguineous population who
      previously had a CMA. Pathogenic CNVs were identified in 32 (14%) cases; ROH
      suggesting uniparental disomy (UPD) in three (1%) cases, and an additional 25
      (11%) individuals were diagnosed with recessive disorders caused by mutations in
      ROH candidate genes, thereby increasing the CMA diagnostic yield to 26%. Among
      the 25 individuals with recessive diseases, 18 had novel mutations in 16 genes
      (ASPM, SPINK5, QARS, MEGF10, SPATA7, GMPPA, ABCA4, SRD5A2, RPGRIP1L, MET,
      SLC12A6, ALDH1A3, TNFRSF11A, FLNB, PHGDH, and FKBP10) including five with
      phenotypic expansion.

PMID- 27717088
TI  - Intralaminar and tectal projections to the subthalamus in the rat.
AB  - Projections from the posterior intralaminar thalamic nuclei and the superior
      colliculus (SC) to the subthalamic nucleus (STN) and the zona incerta (ZI) have
      been described in the primate and rodent. The aims of this study was to
      investigate several questions on these projections, using modern neurotracing
      techniques in rats, to advance our understanding of the role of STN and ZI. We
      examined whether projection patterns to the subthlamus can be used to identify
      homologues of the primate centromedian (CM) and the parafascicular nucleus (Pf)
      in the rodent, the topography of the projection including what percent of
      intralaminar neurons participate in the projections, and electron microscopic
      examination of intralaminar synaptic boutons in STN. The aim on the SC
      subthalamic projection was to examine whether STN is the main target of the
      projection. This study revealed: (i) the areas similar to primate CM and Pf could
      be recognized in the rat; (ii) the Pf-like area sends a very heavy
      topographically organized projection to STN but very sparse projection to ZI,
      which suggested that Pf might control basal ganglia function through STN; (iii)
      the projection from the CM-like area to the subthalamus was very sparse; (iv) Pf
      boutons and randomly sampled asymmetrical synapses had similar distributions on
      the dendrites of STN neurons; and (v) the lateral part of the deep layers of SC
      sends a very heavy projection to ZI and moderate to sparse projection to limited
      parts of STN, suggesting that SC is involved in a limited control of basal
      ganglia function.

PMID- 27717090
TI  - How the truffle got its mate: insights from genetic structure in spontaneous and
      planted Mediterranean populations of Tuber melanosporum.
AB  - The life cycles and dispersal of edible fungi are still poorly known, thus
      limiting our understanding of their evolution and domestication. The prized Tuber
      melanosporum produces fruitbodies (fleshy organs where meiospores mature)
      gathered in natural, spontaneously inoculated forests or harvested in plantations
      of nursery-inoculated trees. Yet, how fruitbodies are formed remains unclear,
      thus limiting yields, and how current domestication attempts affect population
      genetic structure is overlooked. Fruitbodies result from mating between two
      haploid individuals: the maternal parent forms the flesh and the meiospores,
      while the paternal parent only contributes to the meiospores. We analyzed the
      genetic diversity of T. melanosporum comparatively in spontaneous forests vs.
      plantations, using SSR polymorphism of 950 samples from South-East France. All
      populations displayed strong genetic isolation by distance at the metric scale,
      possibly due to animal dispersal, meiospore persistence in soil, and/or exclusion
      of unrelated individuals by vegetative incompatibility. High inbreeding was
      consistently found, suggesting that parents often develop from meiospores
      produced by the same fruitbody. Unlike maternal genotypes, paternal mycelia
      contributed to few fruitbodies each, did not persist over years, and were
      undetectable on tree mycorrhizae. Thus, we postulate that germlings from the soil
      spore bank act as paternal partners. Paternal genetic diversity and outbreeding
      were higher in plantations than in spontaneous truffle-grounds, perhaps because
      truffle growers disperse fruitbodies to maintain inoculation in plantations.
      However, planted and spontaneous populations were not genetically isolated, so
      that T. melanosporum illustrates an early step of domestication where genetic
      structure remains little affected.

PMID- 27717091
TI  - Targeted Synthesis of 2H- and 1T-Phase MoS2 Monolayers for Catalytic Hydrogen
      Evolution.
AB  - Through a facile and effective strategy by employing lithium molten salts the
      controlled synthesis of 2H- and 1T-MoS2 monolayers with high-yield production is
      achieved. Both phases of MoS2 monolayers exhibit high stabilities. When used as a
      catalyst for hydrogen evolution, these phased MoS2 monolayers deliver respective
      advantages in the field of electro- and photo-catalytic hydrogen evolution.

PMID- 27717092
TI  - The autoimmunity-oral microbiome connection.
AB  - To date, there is a major effort in deciphering the role of complex microbial
      communities, especially the oral and gut microbiomes, in the pathogenesis of
      various diseases. Increasing evidence indicates a key role for the oral
      microbiome in autoimmune diseases. In this review article, we discuss links of
      the oral microbiota to a group of autoimmune diseases, that is, Sjogren's
      syndrome (SS), systemic lupus erythematosus (SLE), Crohn's disease (CD), and
      rheumatoid arthritis (RA). We particularly focus on factors that affect the
      balance between the immune system and the composition of microbiota leading to
      dysbiosis, loss of tolerance and subsequent autoimmune disease progression and
      maintenance.

PMID- 27717094
TI  - Terminal differentiation of cortical neurons rapidly remodels RanGAP-mediated
      nuclear transport system.
AB  - Terminal differentiation of neurons is accompanied by irreversible exit from the
      cell cycle and expression of neuronal phenotypes. The molecular mechanism whereby
      committed neuronal progenitors lose their ability to reenter the cell cycle is
      largely unknown. Here, we report that the nuclear transport system is rapidly
      remodeled in primary cortical progenitor cells (CPCs) at the very beginning of
      neuronal terminal differentiation. High levels of Ran GTPase-activating protein 1
      (RanGAP), a key regulator of the Ran GTP-GDP cycle, in primary CPCs are
      drastically reduced upon neuronal induction. Small ubiquitin-like modifier (SUMO)
      2/3-conjugated RanGAP undergoes desumoylation and degradation in neuronally
      committed CPCs, where reduced RanGAP levels impede the nuclear import of
      nucleocytoplasmic shuttling proteins including the DNA replication initiation
      factor Cdc6. Furthermore, RNAi-mediated down-regulation of RanGAP expression in
      undifferentiated CPCs induces neuronal phenotypes including cell cycle exit. Our
      data suggest that remodeling of the RanGAP-mediated nuclear transport system
      plays a key role in cell cycle exit for terminal differentiation of cortical
      neurons.

PMID- 27717095
TI  - Functional Group Interconversion: Decarbonylative Borylation of Esters for the
      Synthesis of Organoboronates.
AB  - A new and efficient nickel-catalyzed decarbonylative borylation reaction of
      carboxylic acid esters with bis(pinacolato)-diboron has been developed. This
      transformation allows access to structurally diverse aryl as well as alkenyl and
      alkyl boronate esters with high reactivity, broad substrate scope, and excellent
      functional-group tolerance. Further experiments show that this protocol can be
      carried out on a gram scale and applied to orthogonal synthetic strategies.

PMID- 27717093
TI  - Spatial variability and reproducibility of GABA-edited MEGA-LASER 3D-MRSI in the
      brain at 3 T.
AB  - The reproducibility of gamma-aminobutyric acid (GABA) quantification results,
      obtained with MRSI, was determined on a 3 T MR scanner in healthy adults. In this
      study, a spiral-encoded, GABA-edited, MEGA-LASER MRSI sequence with real-time
      motion-scanner-instability corrections was applied for robust 3D mapping of
      neurotransmitters in the brain. In particular, the GABA+ (i.e. GABA plus
      macromolecule contamination) and Glx (i.e. glutamate plus glutamine
      contamination) signal was measured. This sequence enables 3D-MRSI with about 3
      cm3 nominal resolution in about 20 min. Since reliable quantification of GABA is
      challenging, the spatial distribution of the inter-subject and intra-subject
      variability of GABA+ and Glx levels was studied via test-retest assessment in 14
      healthy volunteers (seven men-seven women). For both inter-subject and intra
      subject repeated measurement sessions a low coefficient of variation (CV) and a
      high intraclass correlation coefficient (ICC) were found for GABA+ and Glx ratios
      across all evaluated voxels (intra-/inter-subject: GABA+ ratios, CV ~ 8%-ICC >
      0.75; Glx ratios, CV ~ 6%-ICC > 0.70). The same was found in selected brain
      regions for Glx ratios versus GABA+ ratios (CV varied from about 5% versus about
      8% in occipital and parietal regions, to about 8% versus about 10% in the frontal
      area, thalamus, and basal ganglia). These results provide evidence that 3D
      mapping of GABA+ and Glx using the described methodology provides high
      reproducibility for application in clinical and neuroscientific studies.

PMID- 27717096
TI  - Prevalence of Helicobacter pylori infection in newly arrived refugees attending
      the Migrant Health Service, South Australia.
AB  - BACKGROUND: To determine the prevalence of Helicobacter pylori infection in the
      refugee population attending the Migrant Health Service, South Australia,
      identify demographic factors associated with infection and compare prevalence of
      infection in refugees with that of the nonrefugee population in Australia.
      MATERIALS AND METHODS: Cross-sectional study conducted between October 2010 and
      August 2013. Monoclonal stool antigen testing for H. pylori infection is
      performed as part of a comprehensive health assessment for newly arrived
      refugees. The sample population included 922 adults and children. Outcome
      measures were (i) prevalence of H. pylori infection (ii) association between
      demographic factors such as sex, ethnicity and age, and H. pylori infection.
      RESULTS: H. pylori infection was detected in 198 (21.5%) participants (95% CI
      18.9%-24.3%). The odds of infection were lower in females OR 0.71 (95% CI 0.51
      0.98) compared to males. Compared to Middle Eastern participants, the odds of
      infection were 1.75 (95% CI 1.17-2.62) times higher in African and 1.90 (95% CI
      1.10-3.26) times higher in Burmese participants. Infection was not associated
      with age. DISCUSSION AND CONCLUSION: H. pylori infection is common among newly
      arrived refugees. The long latency of infection to development of complications
      and the availability of testing and relatively effective eradication regimens all
      add weight to a decision to screen in this population.

PMID- 27717097
TI  - p16 immunostaining in keratinocytic neoplasia in organ transplant recipients:
      Bowen's disease shows a characteristic pattern.
AB  - BACKGROUND: For selecting therapy, it is important to distinguish different types
      of keratinocytic neoplasia. It is sometimes difficult to make histopathologic
      diagnosis, especially in organ transplant recipients (OTR) who develop numerous
      lesions. METHODS: To investigate p16 immunostaining in different types of
      keratinocytic neoplasia in OTR, we studied 59 actinic keratoses (AK), 51 Bowen' s
      disease (BD), 63 squamous cell carcinomas (SCC), 16 benign keratotic lesions
      (BKL) from 31 OTR patients and 25 controls (eczema and psoriasis). Tissue
      sections were stained for H&E and p16. We scored intensity, proportion and
      distribution of p16 positive lesional cells. RESULTS: In 19% of AK, 92% of BD,
      35% of SCC and 12% of BKL more than 15% of lesional cells were p16-positive. In
      16% of AK, 80% of BD, 18% of SCC and 13% of BKL strong p16 staining was observed.
      BKL, AK and SCC showed focal and patchy staining, BD showed diffuse pattern with
      strong staining of all atypical cells. Sparing of the basal layer was
      predominantly seen in BD. No control specimen showed p16-overexpression.
      CONCLUSIONS: p16 immunostaining shows a characteristic pattern in BD, but not in
      AK, SCC and BKL. It appears useful in recognizing BD, but not in differentiating
      between other keratinocytic neoplasia.

PMID- 27717098
TI  - Neuropeptides shaping the central nervous system development: Spatiotemporal
      actions of VIP and PACAP through complementary signaling pathways.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal peptide (VIP) are neuropeptides with wide, complementary, and
      overlapping distributions in the central and peripheral nervous systems, where
      they exert important regulatory roles in many physiological processes. VIP and
      PACAP display a large range of biological cellular targets and functions in the
      adult nervous system including regulation of neurotransmission and neuroendocrine
      secretion and neuroprotective and neuroimmune responses. As the main focus of the
      present review, VIP and PACAP also have been long implicated in nervous system
      development and maturation through their interaction with the seven transmembrane
      domain G protein-coupled receptors, PAC1, VPAC1, and VPAC2, initiating multiple
      signaling pathways. Compared with PAC1, which solely binds PACAP with very high
      affinity, VPACs exhibit high affinities for both VIP and PACAP but differ from
      each other because of their pharmacological profile for both natural accessory
      peptides and synthetic or chimeric molecules, with agonistic and antagonistic
      properties. Complementary to initial pharmacological studies, transgenic animals
      lacking these neuropeptides or their receptors have been used to further
      characterize the neuroanatomical, electrophysiological, and behavioral roles of
      PACAP and VIP in the developing central nervous system. In this review, we
      recapitulate the critical steps and processes guiding/driving neurodevelopment in
      vertebrates and superimposing the potential contribution of PACAP and VIP
      receptors on the given timeline. We also describe how alterations in VIP/PACAP
      signaling may contribute to both (neuro)developmental and adult pathologies and
      suggest that tuning of VIP/PACAP signaling in a spatiotemporal manner may
      represent a novel avenue for preventive therapies of neurological and psychiatric
      disorders. (c) 2016 Wiley Periodicals, Inc.

PMID- 27717099
TI  - In vivo measurement of membrane permeability and myofiber size in human muscle
      using time-dependent diffusion tensor imaging and the random permeable barrier
      model.
AB  - The time dependence of the diffusion coefficient is a hallmark of tissue
      complexity at the micrometer level. Here we demonstrate how biophysical modeling,
      combined with a specifically tailored diffusion MRI acquisition performing
      diffusion tensor imaging (DTI) for varying diffusion times, can be used to
      determine fiber size and membrane permeability of muscle fibers in vivo. We
      describe the random permeable barrier model (RPBM) and its assumptions, as well
      as the details of stimulated echo DTI acquisition, signal processing steps, and
      potential pitfalls. We illustrate the RPBM method on a few pilot examples
      involving human subjects (previously published as well as new), such as revealing
      myofiber size derived from RPBM increase after training in a calf muscle, and
      size decrease with atrophy in shoulder rotator cuff muscle. Finally, we comment
      on the potential clinical relevance of our results. Copyright (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27717100
TI  - Household experience and costs of seeking measles vaccination in rural Guinea
      Bissau.
AB  - OBJECTIVES: Children younger than 12 months of age are eligible for childhood
      vaccines through the public health system in Guinea-Bissau. To limit open vial
      wastage, a restrictive vial opening policy has been implemented; 10-dose measles
      vaccine vials are only opened if six or more children aged 9-11 months are
      present at the vaccination post. Consequently, mothers who bring their child for
      measles vaccination can be told to return another day. We aimed to describe the
      household experience and estimate household costs of seeking measles vaccination
      in rural Guinea-Bissau. METHODS: Within a national sample of village clusters
      under demographic surveillance, we interviewed mothers of children aged 9-21
      months about their experience with seeking measles vaccination. From information
      about time and money spent, we calculated household costs of seeking measles
      vaccination. RESULTS: We interviewed mothers of 1308 children of whom 1043 (80%)
      had sought measles vaccination at least once. Measles vaccination coverage was
      70% (910/1308). Coverage decreased with increasing distance to the health centre.
      On average, mothers who had taken their child for vaccination took their child
      1.4 times. Mean costs of achieving 70% coverage were 2.04 USD (SD 3.86) per child
      taken for vaccination. Half of the mothers spent more than 2 h seeking
      vaccination and 11% spent money on transportation. CONCLUSIONS: We found several
      indications of missed opportunities for measles vaccination resulting in
      suboptimal coverage. The household costs comprised 3.3% of the average monthly
      income and should be taken into account when assessing the costs of delivering
      vaccinations.

PMID- 27717101
TI  - Calmodulin as a downstream gene of octopamine-OAR alpha1 signalling mediates
      olfactory attraction in gregarious locusts.
AB  - The migratory locust (Locusta migratoria) shows aggregative traits in nymph
      marching bands and swarm formations through mutual olfactory attraction of
      conspecifics. However, olfactory preference in different nymph stages in
      gregarious locusts is not sufficiently explored. In this study, we found that the
      nymph olfactory preference for gregarious volatiles exhibited obvious variations
      at different developmental stages. The gregarious locusts show attractive
      response to conspecific volatiles from the third stadium. Transcriptome
      comparison between third- and fourth-stadium nymphs showed that the G protein
      coupled receptor (GPCR) pathways are significantly enriched. Amongst the genes
      present in GPCR pathways, the expression level of calmodulin in locust brains
      significantly increased from the third- to the fourth-stadium nymphs. Amongst the
      four octopamine receptors (OARs) belonging to the GPCR family, only OAR alpha1
      showed similar expression patterns to those of calmodulin, and knockdown of OAR
      alpha1 reduced the expression level of calmodulin. RNA interference of calmodulin
      decreased locomotion and induced the loss of olfactory attraction in gregarious
      locusts. Moreover, the activation of OAR alpha1 in calmodulin-knockdown locusts
      did not induce olfactory attraction of the nymphs to gregarious volatiles. Thus,
      calmodulin as a downstream gene of octopamine-OAR alpha1 (OA-OAR alpha1)
      signalling mediates olfactory attraction in gregarious locusts. Overall, this
      study provides novel insights into the mechanism of OA-OAR alpha1 signalling
      involved in olfactory attraction of gregarious locusts.

PMID- 27717102
TI  - Heteroatomic Conjugated Polymers and the Spectral Tuning of Electroluminescence
      via a Supramolecular Coordination Strategy.
AB  - The unique electronic structures of heteroatomic conjugated polymers (HCPs) offer
      an attractive platform to tune optoelectronic properties via a supramolecular
      coordination strategy. This study reports on an sp2 nitrogen heteroatom
      containing fluorene-based copolymer namely poly(9,9-dioctylfluorene-co-9,9
      dioctyldiazafluoren-2,7-yl) (PF8-co-DAF8), with ~20% DAF8 units. Tuning the
      optoelectronic properties of PF8-co-DAF8 via supramolecular coordination with a
      Lewis acid (B(C6 F5 )3 or AlCl3 ) is explored. Formation of either the PF8-co
      DAF8-B(C6 F5 )3 or PF8-co-DAF8-AlCl3 adducts reduces the optical gap and causes
      an attendant redshift of the photoluminescence spectra. Controlling the degree
      and strength of the coordination allows the emission color to be tuned from blue
      through to green and yellow. This strategy is successfully implemented for
      polymer light-emitting diodes, confirming the large degree of spectral tuning
      whilst maintaining good device performance. Maximum luminous efficiencies, eta ~
      1.55 cd A-1 @ 2120 cd m-2 , 1.32 cd A-1 @ 1424 cd m-2 , and 2.56 cd A-1 @ 910 cd
      m-2 are, respectively, recorded for the blue-emitting diodes with Commission
      Internationale de L'Eclairage (CIE) (x, y) coordinates = (0.16, 0.16), the white
      emitting diodes with CIE (x, y) = (0.28, 0.38) and the green-emitting diodes with
      CIE (x, y) = (0.33, 0.52). The results highlight the versatility of the
      supramolecular coordination strategy in modifying the electronic structure of
      HCPs.

PMID- 27717103
TI  - Crystal structure of a class-mu glutathione S-transferase from whiteleg shrimp
      Litopenaeus vannamei: structural changes in the xenobiotic binding H-site may
      alter the spectra of molecules bound.
AB  - Glutathione S-transferases (GSTs) are dimeric proteins that play a key role in
      phase II cellular detoxification. Here, the first crystal structure of a GST
      class-mu from marine crustacean shrimp Litopenaeus vannamei is reported at a
      resolution of 2.0 A. The coordinates reported here have the lowest sequence
      identity with previously reported GSTs class-mu deposited at the Protein Data
      Bank (PDB), although they have subtle conformational differences. One key feature
      of GST class-mu from L. vannamei is the active site crevice markedly reduced when
      it is compared with other GSTs class-mu. This finding together with the chemical
      change of residues into the cavity (F112 and Y210) points to a particular
      specialization in which smallest xenobiotics with nonstandard chemical
      characteristics can be bound to the H-site. This suggests that marine organisms
      have evolved structural strategies to provide efficient selectivity toward
      xenobiotics to be disposed of by the phase II detoxification process.

PMID- 27717104
TI  - The First Organocatalytic Cope Rearrangement.
AB  - Exploiting the concept of iminium ion catalysis led to the discovery of the first
      organocatalytic Cope rearrangement of 1,5-hexadiene-2-carboxaldehydes. A
      diazepane catalyst exhibited optimal catalytic efficiency and offers
      possibilities for chiral modification.

PMID- 27717105
TI  - Acute myeloid leukemia in the elderly (age 70 yr or older): long-term survivors.
AB  - OBJECTIVE: Little data exist regarding long-term survival in elderly patients
      with acute myeloid leukemia (AML). METHODS: In view of the fact that most deaths
      occurred during the first 3 yr, this study examined long-term survival in this
      patient population, defined as overall survival for at least 3 yr with the aim to
      determine the number of long-term survivors and to identify factors that might
      impact on longer survival. RESULTS: The criterion for entry into this cohort was
      fulfilled by 57 patients among 302 seen over a 14-yr period (19%): 12 patients
      who never achieved complete remission (CR), 21 patients who relapsed after CR
      achievement, and 24 patients who achieved CR and did not relapse, including three
      patients who died while in CR and 21 patients still alive in first CR at the time
      of analysis. The pretreatment prognostic importance of cytogenetics was still
      apparent. However, some patients with secondary AML and/or unfavorable-risk
      markers belonged to long survivors. The cohort involved mainly patients treated
      by intensive chemotherapy, but also some patients receiving low-intensity
      therapies. CONCLUSION: Improved results should come from a better selection of
      patients to a more 'personalized' therapeutic approach combined with better
      supportive care assessment.

PMID- 27717106
TI  - Differential effects of oxytocin on mouse hippocampal oscillations in vitro.
AB  - The hypothalamic neuropeptide oxytocin (OT) controls childbirth and lactation, is
      involved in social behaviors, plays a role in various psychiatric disorders, and
      has effects on learning and memory. Although behavioral effects of OT have been
      extensively studied, much less is known about its effects on neuronal and network
      activity patterns. Here, we investigate the effect of OT on two major patterns of
      hippocampal network activity in mouse hippocampal slices. We studied different in
      vitro models of gamma-frequency oscillations and sharp wave-ripple complexes (SPW
      R), two patterns implicated in spatial memory formation and memory consolidation
      respectively. Strikingly, we found a profound difference of OT on these distinct,
      mutually exclusive activity patterns. While gamma oscillations where not affected
      by the activation of hippocampal OT receptors, SPW-R were potently and rapidly
      suppressed. Interestingly, the temporal precision of oscillation-coupled spikes
      was enhanced at the same time. Thus, OT exerts strongly different modulatory
      effects on different network patterns, most likely by inhibition of different
      sets of inhibitory interneurons. The observed dichotomy between gamma and SPW-R
      oscillations may have profound effects on the behavioral and cognitive effects of
      OT which are relevant to cognitive processes and to psychiatric diseases.

PMID- 27717107
TI  - Management of patients with ocular manifestations in vesiculobullous disorders
      affecting the mouth.
AB  - Pemphigoid and pemphigus diseases as well as Stevens-Johnson syndrome present as
      vesiculobullous disorders of the skin and may additionally involve both the oral
      cavity and the ocular surface. Ocular involvement ranges from mild irritation and
      dry eye disease to chronic conjunctivitis, symblepharon, eyelid malposition,
      ocular surface scarring and severe visual loss. In addition to diagnostic
      assessments, ophthalmologists must treat the dry eye and meibomian gland
      dysfunction components of these diseases using a stepladder approach, including
      eyelid hygiene and lubricants. Topical anti-inflammatory therapy is used to treat
      acute inflammatory exacerbations of the ocular surface, but it cannot prevent
      scarring alone. Intralesional antimetabolite therapy can cause regression of
      conjunctival pathology in selected cases. Hence, patients with vesiculobullous
      disorders should be managed by a multidisciplinary team representing
      ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal
      medicine and intensive care. Systemic treatments including corticosteroids,
      azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help
      control inflammation. Intravenous immunoglobulins, plasmapheresis and targeted
      antibody therapy can be used in selected, severe and treatment-resistant cases.
      Local surgical management may include debridement of pseudomembranes, lysis of
      symblepharon, amniotic and mucous membrane grafting as well as reconstructive
      procedures. Prospective, multicentre, international studies are recommended to
      further support evidence-based practice.

PMID- 27717109
TI  - Follicular development and morphological changes in the vaginal epithelium during
      the estrous cycle of Galea spixii.
AB  - The current study aimed to determine if characteristics observed in vaginal
      cytology during the estrous cycle of female SYT cavies corresponded with
      proliferation of the vaginal epithelium, characterized by proliferating cell
      nuclear antigen (PCNA) immunolocalization, and with follicular development at
      different phases of the estrous cycle. After determining estrous cycle phases by
      vaginal cytology, females were euthanized at metestrus, diestrus, proestrus, and
      estrus. Histological study of the vaginal epithelium and ovary were then
      performed. Immunohistochemistry for PCNA in vaginal tissue at each cycle phase
      was also performed. Superficial cornified cells and early post-ovulatory
      follicles were found at estrus. Few nuclei below the enucleate superficial cells
      were immunoreactive to PCNA. At metestrus, the vaginal epithelium underwent
      desquamation and lost the superficial cornified cells; basal and intermediate
      cells appeared, and the post-ovulatory follicle formed an early corpus luteum. No
      PCNA immunoreactivity was observed. At diestrus, the corpus luteum was developed,
      and the vaginal epithelium contained basal and intermediate cells. There was PCNA
      immunoreactivity in the cellular nucleus in the germinative stratum of the
      epithelium. Because of the growth and maturation of ovarian follicles, the
      vaginal epithelium suffered intense proliferation at proestrus. Vaginal cytology
      revealed large intermediate cells and nucleated and enucleated superficial
      cornified cells. In the ovary, mature follicles were present. More apparent
      immunoreactivity of PCNA in the germinative layer was found. In summary, we
      inferred that vaginal exfoliative findings matched the proliferation process of
      the vaginal epithelium. PCNA immunolocalization occurred as well as corresponding
      follicular development in the ovaries.

PMID- 27717108
TI  - Blockade of high mobility group box 1 augments antitumor T-cell response induced
      by peptide vaccination as a co-adjuvant.
AB  - High mobility group box 1 (HMGB1) is a member of the family of damage-associated
      molecular patterns, which cause inflammation and trigger innate immunity through
      Toll-like receptors 2/4 and the receptor for advanced glycation end products. We
      examined the effect of glycyrrhizin, a selective inhibitor of HMGB1, on the
      induction of CTLs in mice. B6 mice, either OT-1 spleen cell-transferred or
      untransferred, were immunized with an s.c. injection of OVA257-264 peptide with
      topical imiquimod, and glycyrrhizin was mixed with the antigen peptide.
      Proliferation of OT-1 cells after immunization was enhanced by glycyrrhizin. The
      effect of glycyrrhizin was confirmed in other adjuvant systems, such as CpG
      oligonucleotide and monophosphoryl lipid A, but glycyrrhizin was not effective in
      Freund's incomplete adjuvant system. The augmenting effects of glycyrrhizin were
      also observed in other synthetic HMGB1 inhibitors, gabexate mesilate, nafamostat,
      and sivelestat. Thus, the effects are common to the HMGB1 inhibitors. Induction
      of CTLs detected by gamma-interferon enzyme-linked immunospot assay was similarly
      augmented by glycyrrhizin. In a therapeutic vaccine model, glycyrrhizin inhibited
      the growth of s.c. transplanted EG.7 tumors. Expression of inflammatory cytokines
      in the skin inoculation site was downregulated by glycyrrhizin. These results
      suggest that HMGB1 inhibitors might be useful as a co-adjuvant for peptide
      vaccination with an innate immunity receptor-related adjuvant.

PMID- 27717110
TI  - Hydrophilic Quaternary Ammonium-Group-Containing [FeFe]-Hydrogenase Models:
      Synthesis, Structures, and Electrocatalytic Hydrogen Production.
AB  - The first quaternary ammonium-group-containing [FeFe]-hydrogenase models [(MU
      PDT)Fe2 (CO)4 {kappa2 -(Ph2 P)2 N(CH2 )2 NMe2 BzBr}] (2; PDT=propanedithiolate)
      and [(MU-PDT)Fe2 (CO)4 {MU-(Ph2 P)2 N(CH2 )2 NMe2 BzBr}] (4) have been prepared
      by the quaternization of their precursors [(MU-PDT)Fe2 (CO)4 {kappa2 -(Ph2 P)2
      N(CH2 )2 NMe2 }] (1) and [(MU-PDT)Fe2 (CO)4 {MU-(Ph2 P)2 N(CH2 )2 NMe2 }] (3)
      with benzyl bromide in high yields. Although new complexes 1-4 have been fully
      characterized by spectroscopic and X-ray crystallographic studies, the chelated
      complexes 1 and 2 converted into their bridged isomers 3 and 4 at higher
      temperatures, thus demonstrating that these bridged isomers are thermodynamically
      favorable. An electrochemical study on hydrophilic models 2 and 4 in MeCN and
      MeCN/H2 O as solvents indicates that the reduction potentials are shifted to less
      negative potentials as the water content increases. This outcome implies that
      both 2 and 4 are more easily reduced in the mixed MeCN/H2 O solvent than in MeCN.
      In addition, hydrophilic models 2 and 4 act as electrocatalysts and achieve
      higher icat /ip values and turnover numbers (TONs) in MeCN/H2 O as a solvent than
      in MeCN for the production of hydrogen from the weak acid HOAc.

PMID- 27717111
TI  - Commentary regarding the article: "Lifestyle mediates seasonal changes in
      metabolic health among the Yakut (Sakha) of Northeastern Siberia".

PMID- 27717112
TI  - Activation of cannabinoid receptor 2 attenuates mechanical allodynia and
      neuroinflammatory responses in a chronic post-ischemic pain model of complex
      regional pain syndrome type I in rats.
AB  - Complex regional pain syndrome type 1 (CRPS-I) remains one of the most clinically
      challenging neuropathic pain syndromes and its mechanism has not been fully
      characterized. Cannabinoid receptor 2 (CB2) has emerged as a promising target for
      treating different neuropathic pain syndromes. In neuropathic pain models,
      activated microglia expressing CB2 receptors are seen in the spinal cord.
      Chemokine fractalkine receptor (CX3CR1) plays a substantial role in microglial
      activation and neuroinflammation. We hypothesized that a CB2 agonist could
      modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by
      regulating CB2 and CX3CR1 signaling. We used chronic post-ischemia pain (CPIP) as
      a model of CRPS-I. Rats in the CPIP group exhibited significant hyperemia and
      edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and
      licking). Intraperitoneal administration of MDA7 (a selective CB2 agonist)
      attenuated mechanical allodynia induced by CPIP. MDA7 treatment was found to
      interfere with early events in the CRPS-I neuroinflammatory response by
      suppressing peripheral edema, spinal microglial activation and expression of
      CX3CR1 and CB2 receptors on the microglia in the spinal cord. MDA7 also mitigated
      the loss of intraepidermal nerve fibers induced by CPIP. Neuroprotective effects
      of MDA7 were blocked by a CB2 antagonist, AM630. Our findings suggest that MDA7,
      a novel CB2 agonist, may offer an innovative therapeutic approach for treating
      neuropathic symptoms and neuroinflammatory responses induced by CRPS-I in the
      setting of ischemia and reperfusion injury.

PMID- 27717113
TI  - Incorporation and Remodeling of Bone Block Allografts in the Maxillary
      Reconstruction: A Randomized Clinical Trial.
AB  - BACKGROUND: Severe alveolar atrophy often presents a challenge for the implant
      surgery. The significant lack of bone in the alveolar ridges may compromise the
      final restorations both from the aesthetic and functional standpoints.
      OBJECTIVES: To evaluate the behavior of bone block allografts for the maxillary
      augmentation and to investigate its incorporation, remodeling, and implant
      survival rates in two different healing time points. MATERIAL AND METHODS: Sixty
      six consecutive patients (52 female/14 male, mean age: 57.95 +/- 9.06 years old),
      presenting 113 atrophic alveolar ridges underwent maxillary augmentation with
      fresh-frozen allogeneic bone blocks from tibia. Patients were randomly assigned
      in two groups: Group 1-patients who would wait 4 months for implant placement
      after grafting, and Group 2-patients who would wait 6 months. Events of
      infection, suture dehiscence or mucosal perforation were recorded. Cone-beam
      computed tomography scans were compared volumetrically between the time of the
      grafting surgery and reentry procedure after incorporation. Biopsies were
      collected and subjected to histological, histomorphometric and
      immunehistochemical analysis. RESULTS: A total of 305 implants were placed in the
      reconstructed sites. The mean resorption rate in Group 1 (13.98% +/- 5.59) was
      significantly lower than Group 2 (31.52% +/- 6.31). The amount of calcified
      tissue, newly formed bone and remaining graft particles demonstrated no
      difference between groups. The samples showed evident immunolabeling for the
      podoplanin protein in both groups. The implants cumulative survival rate was
      94.76%. CONCLUSIONS: The findings of the present study indicate that there is a
      significant difference regarding the resorption of the grafts when waiting 4 or 6
      months before placing the implants, even though no difference was found in the
      histological, histomorphometric, and immunohistochemical features. Both 4-month
      and 6-months healing times are suitable for the implant placement.

PMID- 27717114
TI  - A potential insect growth regulator for cockroach control: design, synthesis and
      bioactivity of N-terminal-modified allatostatin analogues.
AB  - BACKGROUND: The FGLa-allatostatins (ASTs) are a family of neuropeptides that can
      inhibit juvenile hormone biosynthesis by the corpora allata (CA) in vitro, and
      therefore they are regarded as insect growth regulator (IGR) candidates for pest
      control. In our previous studies, an AST mimic, H17, was found to have a
      significant effect on JH biosynthesis by cockroach CA, both in vitro and in vivo.
      To discover new potential mimics and explore the substituent effect on the
      inhibition of JH biosynthesis, 30 analogues, modified with various substituents
      on the benzene ring at the N-terminus of lead compound H17, were designed and
      synthesised. Their bioactivity in inhibiting JH biosynthesis by the CA of
      Diploptera punctata and the potency of M9, M10 and M11 in activation of Dippu
      AstR were evaluated. RESULTS: All the analogues showed an effect on JH
      biosynthesis by CA in vitro. M9, M10 and M11 can activate the Dippu-AstR, albeit
      with much lower potency than that of AST 1. M11 also exhibited improved in vitro
      activity (IC50 6.98 nm) in comparison with the lead compound H17 (IC50 29.5 nm).
      In particular, M11 displayed good in vivo activity in inhibiting JH biosynthesis
      and basal oocyte growth. CONCLUSION: The structure-activity relationship studies
      suggest that different positions of substituents on the benzene ring of the
      cinnamic acid can lead to different activities. The para-substitution on the
      benzene ring plays an important role in inhibiting JH biosynthesis in vitro.
      Moreover, M11 is considered to be a potential IGR for cockroach control. (c) 2016
      Society of Chemical Industry.

PMID- 27717115
TI  - Pomegranate juice prevents development of non-alcoholic fatty liver disease in
      rats by attenuating oxidative stress and inflammation.
AB  - BACKGROUND: The effects of pomegranate juice (PJ) on the risk factors of non
      alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have
      been reported previously; however, the effects on NAFLD and its prevention have
      not yet been clarified. The present study aimed to evaluate the effects of PJ
      consumption with respect to the prevention of NAFLD/NASH development. Sprague
      Dawley rats were fed either a high-fat, high sugar diet (model group); a high
      fat, high sugar diet plus PJ (model+PJ); or a chow diet ad libitum for 7 weeks.
      Serum levels of fasting glucose, triglyceride, cholesterol, liver enzymes,
      insulin and hepatic tumor necrosis factor-alpha and tissue growth factor-beta
      gene expression were determined. Hepatic histology was examined by hemotoxylin
      and eosin staining. RESULTS: The model+PJ group had significantly lower hepatic
      steatosis, ballooning, lobular inflammation and portal inflammation (P < 0.001);
      lower hepatic pro-inflammatory and pro-fibrotic gene expression (P < 0.001); and
      lower plasma levels of alanine aminotransferase (P = 0.026), aspartate
      aminotransferase (P = 0.041), insulin (P < 0.001), triglycerides (P = 0.041) and
      glucose (P = 0.009) compared to the model group; however, weight gain, food
      intake and plasma high-density lipoprotein levels were not significantly
      different between these two groups. CONCLUSION: The data obtained in the present
      study indicate that the regular consumption of PJ can prevent NAFLD even in the
      presence of the other risk factors such as obesity, hypercholesterolemia, and
      high energy, fat and sugar intakes. (c) 2016 Society of Chemical Industry.

PMID- 27717116
TI  - Clinical significance of liver histology on outcomes in biliary atresia.
AB  - AIM: Biliary atresia (BA) literature has focussed on the relationship between age
      at Kasai procedure (KP) and post-KP outcomes. This study primarily examines post
      KP outcomes including, 6-month normalisation of bilirubin, 5-year native liver
      survival (NLS), development of portal hypertension (PHT) and incidence of
      ascending cholangitis at a single tertiary paediatric centre in Australia. The
      study also evaluated prognostic factors which may influence these aforementioned
      outcomes. METHODS: Retrospective chart review of all BA cases between 1999 and
      2014. Age at KP, liver biopsy results, use of ursodeoxycholic acid or
      prophylactic antibiotics and occurrence of PHT and ascending cholangitis post-KP
      were recorded and related to the primary post-KP outcome measures. RESULTS: BA
      was diagnosed in 29 patients. Twenty-four of 29 patients underwent KP. Median age
      at KP was 68 days (29-104). Fourteen of 24 (58.3%) had bridging fibrosis and 5 of
      24 (20.8%) had cirrhosis at time of KP. Median follow-up was 8.4 years (2.08
      15.58 years). Bilirubin normalisation within 6 months occurred in 7 of 24 (29.2%)
      patients and 5-year NLS was 45.8% (11/24). Fourteen of 24 (58.3%) had PHT and 18
      of 24 (75%) patients had ascending cholangitis post-KP. Absence of bridging
      fibrosis in liver histology at KP was the only factor to be significantly
      associated with improved 5-year NLS. None of the other variables examined had a
      significant association with either 5-year NLS or bilirubin normalisation by 6
      months. CONCLUSION: Five-year NLS in this series was 45.8%. Absence of bridging
      fibrosis at time of KP was the only factor significantly associated with improved
      5-year NLS.

PMID- 27717117
TI  - Have we significantly underestimated the capacity in the Australian health system
      to treat chronic hepatitis C infection in an interferon-free era?
AB  - BACKGROUND: New antiviral therapies for hepatitis C infection may lead to an
      increase in capacity to treat because of their simplicity and safety. AIMS: To
      determine the likely current capacity of accredited treatment centres in treating
      hepatitis C (HCV) patients with interferon (IFN)-free direct acting antiviral
      (DAA) agents in Australia. METHOD: Data were collected from 22 centres before the
      introduction of DAA therapy - 11 sites from the Study 1 survey and an additional
      11 sites from the Study 2 survey. The sites were selected based on consensus by
      viral hepatitis experts, in consultation with the NSW Agency for Clinical
      Innovation. The services were selected as they were experienced in the delivery
      of IFN-based treatments and/or had knowledge about IFN-free regimens. The sites
      selected offered a mix of metropolitan and regional clinics, opioid substitution
      clinics, Aboriginal services, general practitioner-initiated, criminal justice
      and nurse-led services. Following the survey, the first 3 months of actual
      treatment uptake, since listing in March and May 2016, became available for a
      comparison and were subsequently analysed. RESULTS: The survey indicated that an
      average of 27 h would be required to treat patients with IFN-based regimens. This
      was reduced to an average of 9 h if IFN-free regimens were used. The average
      number of patients on IFN-based treatment regimens per site was 87 per year
      compared to 493 per site if IFN-free therapy was freely available. There is
      capacity in the current health system to treat five times the numbers of patients
      with chronic HCV in Australia. When applying a weighted ratio; the results for
      all centres show a 3.6-fold increase in the capacity to treat with IFN-free
      regimens. However, these numbers may be an underestimate based on the first 3
      months of actual treatment uptake since Pharmaceutical Benefits Scheme listing in
      March and May 2016. CONCLUSION: Although current sites have a significant
      capacity to increase rapidly HCV treatment numbers, expansion of treatment
      settings and new models of care and training may be required to deliver HCV
      treatment to all HCV-infected individuals.

PMID- 27717118
TI  - Diet-related gut bacterial dysbiosis correlates with impaired development,
      increased mortality and Nosema disease in the honeybee (Apis mellifera).
AB  - Dysbiosis, defined as unhealthy shifts in bacterial community composition, can
      lower the colonization resistance of the gut to intrinsic pathogens. Here, we
      determined the effect of diet age and type on the health and bacterial community
      composition of the honeybee (Apis mellifera). We fed newly emerged bees fresh or
      aged diets, and then recorded host development and bacterial community
      composition from four distinct regions of the hosts' digestive tract. Feeding
      fresh pollen or fresh substitute, we found no difference in host mortality, diet
      consumption, development or microbial community composition. In contrast, bees
      fed aged diets suffered impaired development, increased mortality and developed a
      significantly dysbiotic microbiome. The consumption of aged diets resulted in a
      significant reduction in the core ileum bacterium Snodgrassella alvi and a
      corresponding increase in intrinsic pathogen Frischella perrara. Moreover, the
      relative abundance of S. alvi in the ileum was positively correlated with host
      survival and development. The inverse was true for both F. perrara and
      Parasacharibacter apium. Collectively, our findings suggest that the early
      establishment of S. alvi is associated with healthy nurse development and
      potentially excludes F. perrara and P. apium from the ileum. Although at low
      abundance, establishment of the common midgut pathogen Nosema spp. was
      significantly associated with ileum dysbiosis and associated host deficiencies.
      Moreover, dysbiosis in the ileum was reflected in the rectum, mouthparts and
      hypopharyngeal glands, suggesting a systemic host effect. Our findings
      demonstrate that typically occurring alterations in diet quality play a
      significant role in colony health and the establishment of a dysbiotic gut
      microbiome.

PMID- 27717119
TI  - Comparison of acute expansion of bioresorbable vascular scaffolds versus metallic
      drug-eluting stents in different degrees of calcification: An Optical Coherence
      Tomography Study.
AB  - OBJECTIVES: The acute expansion of bioresorbable vascular scaffolds (BRS) and
      drug-eluting stents (DES) in lesions with different extent of calcification was
      compared by Optical Coherence Tomography (OCT). BACKGROUND: The acute mechanical
      performance of polymeric BRS in calcified lesions is poorly understood. METHODS:
      Acute device performance in lesions treated with either BRS(N = 50) or DES (N =
      50) was compared using Optical Coherence Tomography (OCT). According to
      angiographic degree of calcification the lesions were divided in three groups:
      no/mild, moderate and heavy calcification. Device performance was assessed with
      the following parameters by OCT: mean scaffold area, eccentricity index (EI),
      symmetry index (SI) and percentage incomplete strut apposition (ISA). RESULTS:
      One hundred lesions from 85 patients (BRS/DES; 37/48) were analyzed. Scaffold
      area and SI were similar between BRS and DES groups in the three calcification
      subgroups. Compared to DES, EI in BRS was marginally lower in the no/mild
      calcification group (0.86 +/- 0.03 versus 0.88 +/- 0.03, p = 0.018) but was
      similar in the moderate and heavy calcification groups. Compared to DES,
      percentage ISA struts in BRS was similar in the no/mild calcification group and
      was significantly lower in the moderate and heavy calcification groups (2.96 +/-
      2.36 versus 6.78 +/- 4.61%, p = 0.002 and 1.82 +/- 2.40 versus 8.89 +/- 8.25%, p
      = 0.025 respectively). CONCLUSIONS: With adequate lesion preparation,
      implantation of BRS in a population reflective of clinical practice, resulted in
      a similar luminal gain compared to DES as measured by OCT, regardless of the
      degree of angiographic calcification, while acute malapposition is lower with BRS
      in moderately and heavily calcified lesions. The clinical significance of our
      findings warrants further evaluation in future studies. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27717120
TI  - Comb-Like Poly(Ether-Sulfone) Membranes Derived from Planar 6,12-Diaryl-5,11
      Dihydroindolo[3,2-b]Carbazole Monomer for Alkaline Fuel Cells.
AB  - Highly conductive anion exchange membranes (AEMs), along with the ability to
      suppress swelling, are critical but challenging requirements for alkaline fuel
      cell applications. To achieve this criterion, a series of poly(ether sulfone)s
      (PESFs) with flexible alkyl imidazolium pendants attached directly on large
      planar 6,12-bis(4-hydroxyphenyl)-5,11-dihydroindolo[3,2-b]carbazole (DCP) units
      is reported. The planar DCP units stabilize the hydrophobic phase through strong
      pi-pi interactions and also facilitate the formation of ionic conducting channels
      through self assembly of hydrophilic pendants. The AEM prepared here, based on
      rational design, has a relatively low ion exchange capacity (IEC) of 1.86 * 10-3
      mol g-1 and exhibits high hydroxide ion (OH- ) conductivity of 101 * 10-3 S cm-1
      , a low swelling ratio of 9.3% and a water uptake of 39.6%. Furthermore, the AEMs
      reported in this paper have excellent stability in 1 m NaOH solution at 80 
      degrees C over 500 h. Therefore, the synthesized polymers offer a new insight
      into the design of high performance materials for AEMs.

PMID- 27717121
TI  - Molecular characterisation of two alpha-esterase genes involving chlorpyrifos
      detoxification in the diamondback moth, Plutella xylostella.
AB  - BACKGROUND: Carboxylesterases (CarEs) are involved in metabolic detoxification of
      dietary and environmental xenobiotics in insects. However, owing to the
      complexity of the protein family, the involvement of CarEs in insecticide
      metabolism in Plutella xylostella has not been fully elucidated. This study aimed
      to characterise two CarE genes and assess their potential roles in response to
      chlorpyrifos in P. xylostella. RESULTS: Synergistic tests showed that triphenyl
      phosphate decreased the resistance of the third-instar larvae to chlorpyrifos.
      The treatment of the third-instar larvae with chlorpyrifos at the LC30 dose led
      to a significant increase in CarE activity. Two CarE cDNAs (Pxae18 and Pxae28)
      were subsequently sequenced and characterised. Both genes were expressed
      predominantly in the larval midgut. Most importantly, two CarE genes showed
      significantly higher expression in the chlorpyrifos-resistant strain than in the
      susceptible strain. RNAi knockdown of Pxae18 and Pxae28 significantly increased
      the mortality to chlorpyrifos from 40% in the control to 73.8 and 63.3%
      respectively. CONCLUSION: RNAi knockdown of Pxae18 and Pxae28 significantly
      inhibited detoxification ability and increased the mortality in P. xylostella.
      The results indicate that these two CarE genes play important roles in the
      detoxification of chlorpyrifos in P. xylostella. (c) 2016 Society of Chemical
      Industry.

PMID- 27717123
TI  - Craniofacial morphology in pediatric patients with Prader-Willi syndrome: a
      retrospective study.
AB  - OBJECTIVE: To investigate craniofacial characteristics in pediatric patients with
      Prader-Willi syndrome (PWS). SETTING AND SAMPLE POPULATION: A retrospective
      sample of 20 consecutive patients with PWS who had lateral and antero-posterior
      (AP) cephalograms (14 males and six females; average age 10.2 +/- 3 years) was
      compared to 20 controls matched for age and sex (14 males and six females;
      average age 10.5 +/- 3.7 years). MATERIALS AND METHODS: Cephalometric skeletal
      measurements were performed twice at a 1-week interval by one calibrated
      operator, and random error was calculated using Dahlberg's formula. Mean values
      and standard deviations were computed for all variables. Student's t-test for
      independent samples was used to determine significant differences between PWS and
      controls. The level of significance was set at p < 0.05. RESULTS: Cephalometric
      values for the length of the maxilla (p < 0.01), mandibular length (p < 0.05) at
      both the ramus (p < 0.05) and the mandibular body (p < 0.01), and posterior and
      anterior facial height (p < 0.01) were significantly lower in patients with PWS
      compared to controls. The AP cephalometric analysis revealed a significant
      reduction (p < 0.01) in maxillary skeletal width, mandibular skeletal width, and
      interzygomatic distance. CONCLUSIONS: Pediatric patients with PWS seem to have a
      general reduction in certain craniofacial skeletal parameters (i.e., maxillary
      and mandibular length) compared to controls, but this study did not assess the
      overall craniofacial characteristics.

PMID- 27717124
TI  - Is colorectal surgery beyond the age of 80 still feasible with acceptable
      mortality? An analysis of the predictive value of CR-POSSUM and life expectancy
      after hospital discharge.
AB  - AIM: Increased morbidity and mortality could mitigate the positive effect of
      surgery in elderly patients undergoing colorectal resections. This retrospective
      study aims to describe early morbidity and mortality together with long-term
      survival in octogenarians and nonagenarians undergoing colorectal surgery.
      Predictors for in-hospital mortality are identified. The predictive value of CR
      POSSUM is assessed. METHOD: Data on consecutive patients 80 years old or more
      undergoing a colorectal resection in our centre from 2004 until 2010 were
      analysed. RESULTS: Some 286 patients [median age 84 years; interquartile range
      (IQR) 81.6-86.1; 133 men, 47%] underwent a colorectal resection. Median follow-up
      was 32 months (IQR 14.5-51.2). Two hundred and fifty-eight patients (90%) were
      operated on for malignancy. Only 64 patients (22.4%) underwent a laparoscopic
      procedure. Overall median hospital stay was 12 days (IQR 9.0-20.0) and in
      hospital mortality was 9.4%. Seventy-six per cent (n = 170) of patients could
      return home after discharge. The 1-year survival rate was 78.6% (95% CI 73.8
      82.7). Median CR-POSSUM for in-hospital mortality was 12.6% (IQR 11.9-21.0). The
      concordance probability estimate was 0.668 (95% CI 0.609-0.728), reflecting a
      moderate predictive capacity of CR-POSSUM. Once patients had been discharged from
      hospital, life expectancy was similar to that of the Belgian general population.
      CONCLUSION: Colorectal surgery in octogenarians and nonagenarians resulted in a
      considerable in-hospital mortality of about 9%. One-year mortality added an
      additional 12%, which is in concordance with the overall life expectancy at that
      age.

PMID- 27717125
TI  - First metreleptin treatment for generalized lipodystrophy in Turkey.

PMID- 27717127
TI  - Diverse Effects, Complex Causes: Children Use Information About Machines'
      Functional Diversity to Infer Internal Complexity.
AB  - Four studies explored the abilities of 80 adults and 180 children (4-9 years),
      from predominantly middle-class families in the Northeastern United States, to
      use information about machines' observable functional capacities to infer their
      internal, "hidden" mechanistic complexity. Children as young as 4 and 5 years old
      used machines' numbers of functions as indications of complexity and matched
      machines performing more functions with more complex "insides" (Study 1).
      However, only older children (6 and older) and adults used machines' functional
      diversity alone as an indication of complexity (Studies 2-4). The ability to use
      functional diversity as a complexity cue therefore emerges during the early
      school years, well before the use of diversity in most categorical induction
      tasks.

PMID- 27717122
TI  - Genetic variants in CETP increase risk of intracerebral hemorrhage.
AB  - OBJECTIVE: In observational epidemiologic studies, higher plasma high-density
      lipoprotein cholesterol (HDL-C) has been associated with increased risk of
      intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl
      ester transfer protein (CETP) gene activity increase plasma HDL-C; as such,
      medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we
      test the hypothesis that CETP DNA sequence variants associated with higher HDL-C
      also increase risk for ICH. METHODS: We performed 2 candidate-gene analyses of
      CETP. First, we tested individual CETP variants in a discovery cohort of 1,149
      ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625
      cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk
      score comprised of 7 independent variants at the CETP locus and tested this score
      for association with HDL-C as well as ICH risk. RESULTS: Twelve variants within
      CETP demonstrated nominal association with ICH, with the strongest association at
      the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 *
      10-4 ) with no heterogeneity across studies (I2  = 0%). This association was
      replicated in patients of European ancestry (p = 0.03). A genetic score of CETP
      variants found to increase HDL-C by ~2.85mg/dl in the Global Lipids Genetics
      Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39
      * 10-6 ). INTERPRETATION: Genetic variants in CETP associated with increased HDL
      C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition
      and other HDL-raising strategies, further exploration of potential adverse
      cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.

PMID- 27717128
TI  - Mirror-Image Packing Provides a Molecular Basis for the Nanomolar Equipotency of
      Enantiomers of an Experimental Herbicide.
AB  - Programs of drug discovery generally exploit one enantiomer of a chiral compound
      for lead development following the principle that enantiomer recognition is
      central to biological specificity. However, chiral promiscuity has been
      identified for a number of enzyme families, which have shown that mirror-image
      packing can enable opposite enantiomers to be accommodated in an enzyme's active
      site. Reported here is a series of crystallographic studies of complexes between
      an enzyme and a potent experimental herbicide whose chiral center forms an
      essential part of the inhibitor pharmacophore. Initial studies with a racemate at
      1.85 A resolution failed to identify the chirality of the bound inhibitor,
      however, by extending the resolution to 1.1 A and by analyzing high-resolution
      complexes with the enantiopure compounds, we determined that both enantiomers
      make equivalent pseudosymmetric interactions in the active site, thus mimicking
      an achiral reaction intermediate.

PMID- 27717129
TI  - Emergency Department Utilization in Children <36 Months Is Not an Independent
      Risk Factor for Maltreatment.
AB  - BACKGROUND AND OBJECTIVES: Early childhood high-frequency use (HFU) of the
      emergency department (ED) has been endorsed as a marker for increased risk of
      child maltreatment. In a prior analysis of pediatric ED (PED) visits by 16,664
      children, 0-36 months old, we defined early childhood HFU (the 90th percentile)
      as five or more visits. The purpose of this study was to follow HFU patients to
      determine if they had a higher likelihood of reported maltreatment. METHODS: This
      is a single-center, cross-sectional, observational study of the association
      between PED use in early life and subsequent intervention by child protective
      services (CPS). CPS data were obtained from a Department of Social Services
      database for subjects meeting criteria for PED HFU as well as sex, race, and
      ethnicity-matched controls. Multivariable analyses were performed to assess if
      HFU was independently associated with child maltreatment. RESULTS: While CPS
      involvement was more highly represented in the group with PED HFU, so were many
      confounding variables such as African American race, history of hospital
      admissions, and social work consultations in the PED for any reason. HFU, by
      itself, is not a risk factor for a major intervention by CPS. CONCLUSIONS: In
      efforts to identify children at risk for maltreatment, objective assessments such
      as PED utilization are potential markers to utilize to aid in recognition.
      Unfortunately, there are many risk factors for increased PED utilization that act
      as confounders for this marker. Future work is necessary to identify children at
      risk for maltreatment in the ED.

PMID- 27717126
TI  - Near-normalization of glycaemic control with glucagon-like peptide-1 receptor
      agonist treatment combined with exercise in patients with type 2 diabetes.
AB  - AIMS: To investigate the effects of exercise in combination with a glucagon-like
      peptide-1 receptor agonist (GLP-1RA), liraglutide, or placebo for the treatment
      of type 2 diabetes. METHODS: Thirty-three overweight, dysregulated and sedentary
      patients with type 2 diabetes were randomly allocated to 16 weeks of either
      exercise and liraglutide or exercise and placebo. Both groups had three
      supervised 60-minute training sessions per week including spinning and resistance
      training. RESULTS: Glycated haemoglobin (HbA1c) levels dropped by a mean +/-
      standard deviation of 2.0% +/- 1.2% (from 8.2% +/- 1.4%) in the exercise plus
      liraglutide group vs 0.3% +/- 0.9% (from 8.0% +/- 1.2%) in the exercise plus
      placebo group ( P < .001), and body weight was reduced more with liraglutide (
      3.4 +/- 2.9 kg vs -1.6 +/- 2.3 kg; P < .001). Compared with baseline, similar
      reductions were seen in body fat (exercise plus liraglutide: -2.5% +/- 1.4% [ P <
      .001]; exercise plus placebo: -2.2% +/- 1.9% [ P < .001]) and similar increases
      were observed in maximum oxygen uptake (exercise plus liraglutide: 0.5 +/- 0.5 L
      O2 /min [ P < .001]; exercise plus placebo: 0.4 +/- 0.4 L O2 /min [ P = .002]).
      Greater reductions in fasting plasma glucose (-3.4 +/- 2.3 mM vs -0.3 +/- 2.6 mM,
      P < .001) and systolic blood pressure (-5.4 +/- 7.4 mm Hg vs -0.6 +/- 11.1 mm Hg,
      P < .01) were seen with exercise plus liraglutide vs exercise plus placebo. The
      two groups experienced similar increases in quality of life during the
      intervention. CONCLUSIONS: In obese patients with type 2 diabetes, exercise
      combined with GLP-1RA treatment near-normalized HbA1c levels and caused a robust
      weight loss when compared with placebo. These results suggest that a combination
      of exercise and GLP-1RA treatment is effective in type 2 diabetes.

PMID- 27717131
TI  - Directional Fluid Transport in Thin Porous Materials and its Functional
      Applications.
AB  - Directional fluid motion driven by the surface property of solid substrate is
      highly desirable for manipulating microfluidic liquid and collecting water from
      humid air. Studies on such liquid motion have been confined to dense material
      surfaces such as flat panels and single filaments. Recently, directional fluid
      transport through the thickness of thin porous materials has been reported by
      several research groups. Their studies not only attract fundamental, experimental
      and theoretical interest but also open novel application opportunities. This
      review article summarizes research progress in directional fluid transport across
      thin porous materials. It focuses on the materials preparation, basic properties
      associated with directional fluid transport in thin porous media, and their
      application development. The porous substrates, type of transporting fluids,
      structure-property attributes, and possible directional fluid transport mechanism
      are discussed. A perspective for future development in this field is proposed.

PMID- 27717130
TI  - Glucagon-like peptide-1 receptor agonists compared with basal insulins for the
      treatment of type 2 diabetes mellitus: a systematic review and meta-analysis.
AB  - AIMS: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs)
      have been approved to treat people with type 2 diabetes. These agents are
      considered for use at the same point in the treatment paradigm as basal insulins.
      A comprehensive comparison of these drug classes, therefore, can help inform
      treatment decisions. This systematic review and meta-analysis assessed the
      clinical efficacy and safety of GLP-1 RAs compared with basal insulins. MATERIALS
      AND METHODS: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched.
      Randomized clinical trials (RCTs) of >=16 weeks' duration comparing GLP-1 RAs vs
      basal insulins in adults with type 2 diabetes inadequately controlled with oral
      antihyperglycemic drugs were included. Data on the change from baseline to 26
      weeks (+/-10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as
      the proportion of patients experiencing hypoglycaemia, were extracted. Fixed
      effect pairwise meta-analyses were conducted where data were available from >=2
      studies. RESULTS: Fifteen RCTs were identified and 11 were meta-analysed. The
      once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led
      to greater, statistically significant mean HbA1c reductions vs basal insulins
      (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [
      0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not
      (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight
      reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal
      insulins. Interpretation of the analysis of hypoglycaemia was limited by
      inconsistent definitions and reporting. Because of the limited number of
      available studies sensitivity analyses to explore heterogeneity could not be
      conducted. CONCLUSIONS: Although weight reduction is seen with all GLP-1 RA's,
      only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate
      significant HbA1c reductions when compared to basal insulins.

PMID- 27717132
TI  - A Novel Bioinspired Continuous Unidirectional Liquid Spreading Surface Structure
      from the Peristome Surface of Nepenthes alata.
AB  - A novel unidirectional liquid spreading surface with an inclined arc pitted
      groove, inspired by the continuous unidirectional liquid spreading mechanism on
      the peristome surface of N. alata, is explored and fabricated by two-step UV
      lithography. Its superior unidirectional liquid spreading capability to that of
      other surface patterns is demonstrated, and its unidirectional liquid spreading
      mechanism is investigated.

PMID- 27717134
TI  - Ontogeny of modern human longitudinal body and transverse shoulder proportions.
AB  - OBJECTIVES: Whereas variation of modern human adult body size and shape has been
      widely studied in the context of ecogeographical clines, little is known about
      the differential growth patterns of transverse and longitudinal dimensions among
      human populations. Our study explored the ontogenetic variation of those body
      proportions in modern humans. METHODS: We compared results from four different
      approaches to study cross-sectional skeletal samples of Africans (n = 43),
      Amerindians (n = 69) and Europeans (n = 40) from 0 to 14 years of age. Clavicle,
      humerus, and femur intermetaphyseal lengths, and femoral distal metaphyseal
      breadth, were measured. Average ontogenetic trajectories were computed in order
      to compare the growth patterns of the three groups. RESULTS: Our findings
      demonstrated that the three geographical groups shared similar absolute and
      relative patterns of change with age for the four dimensions considered. Although
      interpopulation differences existed in transverse to longitudinal as well as in
      interlimb proportions, those differences did not seem to remain constant
      throughout ontogeny, similar to what has been shown for intralimb proportions.
      Growth rates of transverse shoulder proportions differed between populations from
      different regions after 10 years, whereas those for longitudinal proportions were
      very similar. CONCLUSIONS: The ontogeny of transverse shoulder proportions is
      more complex than what is observed for bi-iliac breadth, suggesting that
      transverse shoulder to limb proportions are not solely influenced by
      ecogeographical conditions. Our analysis demonstrates that methodologies that
      incorporate critical dimensions of body form could shed new light on human
      adaptation in both paleontological and neontological contexts.

PMID- 27717133
TI  - The fractionation of adipose tissue procedure to obtain stromal vascular
      fractions for regenerative purposes.
AB  - Autologous adipose tissue transplantation is clinically used to reduce dermal
      scarring and to restore volume loss. The therapeutic benefit on tissue damage
      more likely depends on the stromal vascular fraction of adipose tissue than on
      the adipocyte fraction. This stromal vascular fraction can be obtained by
      dissociation of adipose tissue, either enzymatically or mechanical. Enzymatic
      dissociation procedures are time-consuming and expensive. Therefore, we developed
      a new inexpensive mechanical dissociation procedure to obtain the stromal
      vascular fraction from adipose tissue in a time sparing way, which is directly
      available for therapeutic injection. This mechanical dissociation procedure is
      denoted as the fractionation of adipose tissue (FAT) procedure. The FAT procedure
      was performed in eleven patients. The composition of the FAT-stromal vascular
      fraction was characterized by immunohistochemistry. Adipose derived stromal cells
      isolated from the FAT-stromal vascular fraction were compared with adipose
      derived stromal cells isolated from nondissociated adipose tissue (control) for
      their CD-surface marker expression, differentiation and colony forming unit
      capacity. Case reports demonstrated the therapeutic effect of the FAT-stromal
      vascular fraction. The FAT-stromal vascular fraction is an enrichment of
      extracellular matrix containing a microvasculature and culturable adipose derived
      stromal cells. Adipose derived stromal cells isolated from FAT-stromal vascular
      fraction did not differ from adipose derived stromal cells isolated from the
      control group in CD-surface marker expression, differentiation and colony forming
      unit capacity. The FAT procedure is a rapid effective mechanical dissociation
      procedure to generate FAT-stromal vascular fraction ready for injection with all
      its therapeutic components of adipose tissue: it contains culturable adipose
      derived stromal cells embedded in their natural supportive extracellular matrix
      together with the microvasculature.

PMID- 27717135
TI  - Progress and development of analytical methods for gibberellins.
AB  - Gibberellins, as a group of phytohormones, exhibit a wide variety of bio
      functions within plant growth and development, which have been used to increase
      crop yields. Many analytical procedures, therefore, have been developed for the
      determination of the types and levels of endogenous and exogenous gibberellins.
      As plant tissues contain gibberellins in trace amounts (usually at the level of
      nanogram per gram fresh weight or even lower), the sample pre-treatment steps
      (extraction, pre-concentration, and purification) for gibberellins are reviewed
      in details. The primary focus of this comprehensive review is on the various
      analytical methods designed to meet the requirements for gibberellins analyses in
      complex matrices with particular emphasis on high-throughput analytical methods,
      such as gas chromatography, liquid chromatography, and capillary electrophoresis,
      mostly combined with mass spectrometry. The advantages and drawbacks of the each
      described analytical method are discussed. The overall aim of this review is to
      provide a comprehensive and critical view on the different analytical methods
      nowadays employed to analyze gibberellins in complex sample matrices and their
      foreseeable trends.

PMID- 27717136
TI  - The implicit sociometer effect and the moderating role of relational self
      construal.
AB  - The present study examined how negative feedback influenced implicit self
      evaluations and how individuals' level of relational self-construal (RelSC)
      moderated these relationships. One hundred Chinese university students completed
      the relational-interdependent self-construal scale and were randomly assigned
      into one of three conditions (social exclusion, personal failure, or control).
      After receiving the manipulation, participants completed two Brief Implicit
      Association Tests (BIATs) that measured their implicit self-liking and self
      competence. The results indicated that people with a highly RelSC typically had
      higher implicit self-liking, but they decreased their implicit self-liking more
      than those with a low RelSC after experiencing social exclusion. However, RelSC
      did not influence the effect of personal failure on implicit self-liking. In
      addition, RelSC was not associated with implicit self-competence in any
      situation.

PMID- 27717137
TI  - Corrosion-Activated Chemotherapeutic Function of Nanoparticulate Platinum as a
      Cisplatin Resistance-Overcoming Prodrug with Limited Autophagy Induction.
AB  - Despite nanoparticulate platinum (nano-Pt) has been validated to be acting as a
      platinum-based prodrug for anticancer therapy, the key factor in controlling its
      cytotoxicity remains to be clarified. In this study, it is found that the
      corrosion susceptibility of nano-Pt can be triggered by inducing the oxidization
      of superficial Pt atoms, which can kill both cisplatin-sensitive/resistance
      cancer cells. Direct evidence in the oxidization of superficial Pt atoms is
      validated to observe the formation of platinum oxides by X-ray absorption
      spectroscopy. The cytotoxicity is originated from the dissolution of nano-Pt
      followed by the release of highly toxic Pt ions during the corrosion process.
      Additionally, the limiting autophagy induction by nano-Pt might prevent cancer
      cells from acquiring autophagy-related drug resistance. With such advantages, the
      possibility of further autophagy-related drug resistance could be substantially
      reduced or even eliminated in cancer cells treated with nano-Pt. Moreover, nano
      Pt is demonstrated to kill cisplatin-resistant cancer cells not only by inducing
      apoptosis but also by inducing necrosis for pro-inflammatory/inflammatory
      responses. Thus, nano-Pt treatment might bring additional therapeutic benefits by
      regulating immunological responses in tumor microenvironment. These findings
      support the idea that utilizing nano-Pt for its cytotoxic effects might
      potentially benefit patients with cisplatin resistance in clinical chemotherapy.

PMID- 27717138
TI  - Mesoporous and Nanostructured TiO2 layer with Ultra-High Loading on Nitrogen
      Doped Carbon Foams as Flexible and Free-Standing Electrodes for Lithium-Ion
      Batteries.
AB  - A simple and green method is developed for the preparation of nanostructured TiO2
      supported on nitrogen-doped carbon foams (NCFs) as a free-standing and flexible
      electrode for lithium-ion batteries (LIBs), in which the TiO2 with 2.5-4 times
      higher loading than the conventional TiO2 -based flexible electrodes acts as the
      active material. In addition, the NCFs act as a flexible substrate and efficient
      conductive networks. The nanocrystalline TiO2 with a uniform size of ~10 nm form
      a mesoporous layer covering the wall of the carbon foam. When used directly as a
      flexible electrode in a LIB, a capacity of 188 mA h g-1 is achieved at a current
      density of 200 mA g-1 for a potential window of 1.0-3.0 V, and a specific
      capacity of 149 mA h g-1 after 100 cycles at a current density of 1000 mA g-1 is
      maintained. The highly conductive NCF and flexible network, the mesoporous
      structure and nanocrystalline size of the TiO2 phase, the firm adhesion of TiO2
      over the wall of the NCFs, the small volume change in the TiO2 during the
      charge/discharge processes, and the high cut-off potential contribute to the
      excellent capacity, rate capability, and cycling stability of the TiO2 /NCFs
      flexible electrode.

PMID- 27717139
TI  - Vps35-dependent recycling of Trem2 regulates microglial function.
AB  - Triggering receptor expressed on myeloid cells 2 (Trem2), an immune-modulatory
      receptor, is preferentially expressed in microglia of central nervous system.
      Trem2 might be involved in the development of Alzheimer's disease (AD) through
      regulating the inflammatory responses and phagocytosis of microglia. However, the
      intracellular trafficking of Trem2 remains unclear. In this study, we showed that
      Trem2 in the plasma membrane underwent endocytosis and recycling. Trem2 is
      internalized in a clathrin-dependent manner and then recycled back to the plasma
      membrane through vacuolar protein sorting 35 (Vps35), the key component of cargo
      recognition core of retromer complex, but not Rab11. When Vps35 is knocked down,
      Trem2 accumulated in the lysosomes but was not degraded. More importantly, Vps35
      deficiency leads to excessive lipopolysaccharide (LPS)-induced inducible nitric
      oxide synthase (iNOS) expression and IL-6 production, which can be abolished by
      Trem2 overexpression. Furthermore, R47H Trem2, an AD-associated mutant, failed to
      interact with Vps35 and became unstable compared with wild-type Trem2. Our study
      suggests that Vps35/retromer is responsible for recycling of Trem2 in the
      regulation of microglial function such as proinflammatory responses, whereas R47H
      mutation impairs Trem2 trafficking, which might contribute to AD.

PMID- 27717140
TI  - Wafer Scale Phase-Engineered 1T- and 2H-MoSe2 /Mo Core-Shell 3D-Hierarchical
      Nanostructures toward Efficient Electrocatalytic Hydrogen Evolution Reaction.
AB  - The necessity for new sources for greener and cleaner energy production to
      replace the existing ones has been increasingly growing in recent years. Of those
      new sources, the hydrogen evolution reaction has a large potential. In this work,
      for the first time, MoSe2 /Mo core-shell 3D-hierarchical nanostructures are
      created, which are derived from the Mo 3D-hierarchical nanostructures through a
      low-temperature plasma-assisted selenization process with controlled shapes grown
      by a glancing angle deposition system.

PMID- 27717141
TI  - One-Step Microfluidic Fabrication of Polyelectrolyte Microcapsules in Aqueous
      Conditions for Protein Release.
AB  - We report a microfluidic approach for one-step fabrication of polyelectrolyte
      microcapsules in aqueous conditions. Using two immiscible aqueous polymer
      solutions, we generate transient water-in-water-in-water double emulsion droplets
      and use them as templates to fabricate polyelectrolyte microcapsules. The capsule
      shell is formed by the complexation of oppositely charged polyelectrolytes at the
      immiscible interface. We find that attractive electrostatic interactions can
      significantly prolong the release of charged molecules. Moreover, we demonstrate
      the application of these microcapsules in encapsulation and release of proteins
      without impairing their biological activities. Our platform should benefit a wide
      range of applications that require encapsulation and sustained release of
      molecules in aqueous environments.

PMID- 27717142
TI  - Structure-activity relationship of caffeic acid phenethyl ester analogs as new 5
      lipoxygenase inhibitors.
AB  - Leukotrienes (LTs) are a class of lipid mediators implicated in numerous
      inflammatory disorders. Caffeic acid phenethyl ester (CAPE) possesses potent anti
      LTs activity through the inhibition of 5-lipoxygenase (5-LO), the key enzyme in
      the biosynthesis of LTs. In this study, we describe the design and synthesis of
      CAPE analogs as radical scavengers and 5-LO inhibitors. Caffeic esters bearing
      propargyl and allyl linkers between the caffeoyl and aryl moieties (4a-i and 5a
      i, respectively) were synthesized by Sonogashira and Heck cross-coupling
      reactions to probe the effects of flexibility and aryl substitution on 5-LO
      inhibition. Caffeoyl alcohol and ethers (6, 7a-b) as well as caffeoyl aldehyde
      and ketones (8a-e) were synthesized to elucidate the importance of the ester
      linkage for inhibitory activity. All tested compounds proved to be good radical
      scavengers (IC50 of 10-30 MUm). After preliminary anti-LTs activity screening in
      HEK293 cell models, 5-LO inhibition potential of selected compounds was
      determined in human polymorphonuclear leukocytes (PMNL). Most screened compounds
      outperformed CAPE 3 in concentration-dependent assays on PMNL, with ester dimers
      4i and 5i along with caffeoyl ethers 7a-b being roughly eight-, seven-, and 16
      fold more potent than Zileuton, with IC50 values of 0.36, 0.43, and 0.18 MUm,
      respectively.

PMID- 27717143
TI  - Assessment of analytical methods to determine pyrethroids content of bednets.
AB  - OBJECTIVE: To present and evaluate simple, cost-effective tests to determine the
      amount of insecticide on treated materials. METHODS: We developed and evaluated a
      competitive immunoassay on two different platforms: a label-free impedimetric
      biosensor (EIS biosensor) and a lateral flow. Both approaches were validated by
      gas chromatography (GC) and ELISA, gold standards for analytical methods and
      immunoassays, respectively. Finally, commercially available pyrethroid-treated
      ITN samples were analysed. Different extraction methods were evaluated. RESULTS:
      Insecticide extraction by direct infusion of the ITN samples with dichloromethane
      and dioxane showed recovery efficiencies around 100% for insecticide-coated
      bednets, and >70% for insecticide-incorporated bednets. These results were
      comparable to those obtained with standard sonication methods. The competitive
      immunoassay characterisation with ELISA presented a dynamic range between 12 nm
      and 1.5 MUm (coefficient of variation (CV) below 5%), with an IC50 at 138 nm, and
      a limit of detection (LOD) of 3.2 nm. EIS biosensor had a linear range between
      1.7 nm and 61 nm (CV around 14%), with an IC50 at 10.4 nm, and a LOD of 0.6 nm.
      Finally, the lateral flow approach showed a dynamic range between 150 nm and 1.5
      MUm, an IC50 at 505 nm and a LOD of 67 nm. CONCLUSIONS: ELISA can replace
      chromatography as an accurate laboratory technique to determine insecticide
      concentration in bednets. The lateral flow approach developed can be used to
      estimate ITN insecticide concentration in the field. This new technology, coupled
      to the new extraction methods, should provide reliable guidelines for ITN use and
      replacement in the field.

PMID- 27717144
TI  - An ex vivo porcine skin model to evaluate pressure-reducing devices of different
      mechanical properties used for pressure ulcer prevention.
AB  - Pressure ulcers are complex wounds caused by pressure- and shear-induced trauma
      to skin and underlying tissues. Pressure-reducing devices, such as dressings,
      have been shown to successfully reduce pressure ulcer incidence, when used in
      adjunct to pressure ulcer preventative care. While pressure-reducing devices are
      available in a range of materials, with differing mechanical properties,
      understanding of how a material's mechanical properties will influence clinical
      efficacy remains limited. The aim of this study was to establish a standardized
      ex vivo model to allow comparison of the cell protection potential of two gel
      like pressure-reducing devices with differing mechanical properties (elastic
      moduli of 77 vs. 35 kPa). The devices also displayed differing energy dissipation
      under compressive loading, and resisted strain differently under constant load in
      compressive creep tests. To evaluate biological efficacy we employed a new ex
      vivo porcine skin model, with a confirmed elastic moduli closely matching that of
      human skin (113 vs. 119 kPa, respectively). Static loads up to 20 kPa were
      applied to porcine skin ex vivo with subsequent evaluation of pressure-induced
      cell death and cytokine release. Pressure application alone increased the
      percentage of epidermal apoptotic cells from less than 2% to over 40%, and
      increased cellular secretion of the pro-inflammatory cytokine TNF-alpha. Co
      application of a pressure-reducing device significantly reduced both cellular
      apoptosis and cytokine production, protecting against cellular damage. These data
      reveal new insight into the relationship between mechanical properties of
      pressure-reducing devices and their biological effects. After appropriate
      validation of these results in clinical pressure ulcer prevention with all tissue
      layers present between the bony prominence and external surface, this ex vivo
      porcine skin model could be widely employed to optimize design and evaluation of
      devices aimed at reducing pressure-induced skin damage.

PMID- 27717145
TI  - Recent applications of hydrophilic interaction liquid chromatography in
      pharmaceutical analysis.
AB  - Hydrophilic interaction liquid chromatography, an alternative liquid
      chromatography mode, is of particular interest in separating hydrophilic and
      polar ionic compounds. Compared with traditional liquid chromatography
      techniques, hydrophilic interaction liquid chromatography offers specific
      advantages mainly including: (1) relatively green and water-soluble mobile phase
      composition, which enhances the solubility of hydrophilic and polar ionic
      compounds; (2) no need for ion-pairing reagents and high content of organic
      solvent, which benefits mass spectrometry detection; (3) high orthogonality to
      reverse-phase liquid chromatography, well adapted to two-dimensional liquid
      chromatography for complicated samples. Therefore, hydrophilic interaction liquid
      chromatography has been rapidly developed in many areas over the past decades.
      This review summarizes the recent progress (from 2012 to July 2016) of
      hydrophilic interaction liquid chromatography in pharmaceutical analysis, with
      the focus on detecting chemical drugs in various matrices, charactering active
      compounds of natural products and assessing biotherapeutics through typical
      structure unit. Moreover, the retention mechanism and behavior of analytes in
      hydrophilic interaction liquid chromatography as well as some novel hydrophilic
      interaction liquid chromatography columns used for pharmaceutical analysis are
      also described.

PMID- 27717146
TI  - Hyperdiploidy as a rare event that accompanies poor prognosis markers in CLL.
AB  - : The presence of chromosomal gains other than trisomy 12 in chronic lymphocytic
      leukaemia (CLL) is unusual. However, some patients may show gains on several
      chromosomes simultaneously suggesting a hyperdiploid karyotype. OBJECTIVE: The
      objective of this study was to analyse by FISH the frequency and prognostic
      impact of hyperdiploidy in CLL. METHOD: A review of 1359 consecutive cases
      diagnosed with CLL referred for FISH analysis to a unique institution was carried
      out. Hyperdiploidy was considered when a gain of at least three of the five FISH
      probes used was observed. RESULTS: Seven cases (0.51%) with hyperdiploidy were
      found, confirming that it is a rare event in this disease. Although most patients
      presented with early Binet stages at diagnosis, six of seven (86%) shortly
      progressed. The median of time to the first therapy (TTFT) and overall survival
      (OS) for the patients with hyperdiploidy were short (1.4 months and 20 months,
      respectively). Moreover, comparing them with a control group of patients (non
      hyperdiploid) with completed follow-up data, TTFT and OS of the patients with
      hyperdiploidy were significantly shorter than the control group. CONCLUSION: The
      presence of hyperdiploidy is uncommon and probably associated with poor
      prognostic markers in CLL.

PMID- 27717147
TI  - A Silver(I)-Estrogen Nanocluster: GSH Sensitivity and Targeting Suppression on
      HepG2 Cell.
AB  - A structure-determined silver nanocluster of [Ag10 (Eth)4 (CF3 COO)6 (CH3 OH)3
      ].3C-H3 OH (Eth = ethisterone) (1), is firstly demonstrated by self-assembly of
      silver salt and ethisterone. Due to the thiophilicity of silver(I) ions, complex
      1 shows reactivity with glutathione (GSH) molecules in solution and induces the
      fluorescence quenching behavior. Thus, complex 1 can be used as a fluorescent
      sensor for GSH. In consideration of the higher level of GSH in cancerous cells,
      complex 1 presents significant tumor suppression reactivity toward the human
      hepatocellular carcinoma (HepG2) cells with IC50 value of 165 * 10-9 m.
      Especially, complex 1 displays 3.4-fold higher in vitro cytotoxicity to HepG2
      cells than that of the normal CCC-HEL-1 cells, which makes complex 1 a potential
      targeting suppression agent for cancerous cells. The molecular design of complex
      1 not only generates a new medicine-silver(I) cluster family, but also opens a
      new avenue to the targeting anticancer organosilver(I) materials.

PMID- 27717148
TI  - A Macrocyclic Ruthenium(III) Complex Inhibits Angiogenesis with Down-Regulation
      of Vascular Endothelial Growth Factor Receptor-2 and Suppresses Tumor Growth In
      Vivo.
AB  - A macrocyclic ruthenium(III) complex [RuIII (N2 O2 )Cl2 ]Cl (Ru-1) is reported as
      an inhibitor of angiogenesis and an anti-tumor compound. The complex is
      relatively non-cytotoxic towards endothelial and cancer cell lines in vitro, but
      specifically inhibited the processes of angiogenic endothelial cell tube
      formation and cancer cell invasion. Moreover, compared with known anti-cancer
      ruthenium complexes, Ru-1 is distinct in that it suppressed the expression of
      vascular endothelial growth factor receptor-2 (VEGFR2), and the associated
      downstream signaling that is crucial to tumor angiogenesis. In addition, in vivo
      studies showed that Ru-1 inhibited angiogenesis in a zebrafish model and
      suppressed tumor growth in nude mice bearing cancer xenografts.

PMID- 27717150
TI  - Carbon Dots/NiCo2 O4 Nanocomposites with Various Morphologies for High
      Performance Supercapacitors.
AB  - A series of carbon dots/NiCo2 O4 composites with various morphologies are
      prepared and tested for supercapacitors. These samples have good electrical
      conductivities and efficient ions transport paths, so they exhibit high specific
      capacitances, superior rate performances, and high cycling stabilities. The
      optimal composite for hybrid supercapacitor exhibits a high energy density up to
      62.0 Wh kg-1 .

PMID- 27717149
TI  - Microfluidic Platforms for Yeast-Based Aging Studies.
AB  - The budding yeast Saccharomyces cerevisiae has been a powerful model for the
      study of aging and has enabled significant contributions to our understanding of
      basic mechanisms of aging in eukaryotic cells. However, the laborious low
      throughput nature of conventional methods of performing aging assays limits the
      pace of discoveries in this field. Some of the technical challenges of
      conventional aging assay methods can be overcome by use of microfluidic systems
      coupled to time-lapse microscopy. One of the major advantages is the ability of a
      microfluidic system to perform long-term cell culture under well-defined
      environmental conditions while tracking individual yeast. Here, recent
      advancements in microfluidic platforms for various yeast-based studies including
      replicative lifespan assay, long-term culture and imaging, gene expression, and
      cell signaling are discussed. In addition, emerging problems and limitations of
      current microfluidic approaches are examined and perspectives on the future
      development of this dynamic field are presented.

PMID- 27717152
TI  - Toward Precision Medicine: A Cancer Molecular Subtyping Nano-Strategy for RNA
      Biomarkers in Tumor and Urine.
AB  - Cancer is a heterogeneous disease which manifests as different molecular subtypes
      due to the complex nature of tumor initiation, progression, and metastasis. The
      concept of precision medicine aims to exploit this cancer heterogeneity by
      incorporating diagnostic technology to characterize each cancer patient's
      molecular subtype for tailored treatments. To characterize cancer molecular
      subtypes accurately, a suite of multiplexed bioassays have currently been
      developed to detect multiple oncogenic biomarkers. Despite the reliability of
      current multiplexed detection techniques, novel strategies are still needed to
      resolve limitations such as long assay time, complex protocols, and difficulty in
      interpreting broad overlapping spectral peaks of conventional fluorescence
      readouts. Herein a rapid (80 min) multiplexed platform strategy for subtyping
      prostate cancer tumor and urine samples based on their RNA biomarker profiles is
      presented. This is achieved by combining rapid multiplexed isothermal reverse
      transcription-recombinase polymerase amplification (RT-RPA) of target RNA
      biomarkers with surface-enhanced Raman spectroscopy (SERS) nanotags for "one-pot"
      readout. This is the first translational application of a RT-RPA/SERS-based
      platform for multiplexed cancer biomarker detection to address a clinical need.
      With excellent sensitivity of 200 zmol (100 copies) and specificity, we believed
      that this platform methodology could be a useful tool for rapid multiplexed
      subtyping of cancers.

PMID- 27717151
TI  - Synthesis and Thermophysical Properties of Ether-Functionalized Sulfonium Ionic
      Liquids as Potential Electrolytes for Electrochemical Applications.
AB  - During this work, a novel series of hydrophobic room temperature ionic liquids
      (ILs) based on five ether functionalized sulfonium cations bearing the
      bis{(trifluoromethyl)sulfonyl}imide, [NTf2 ]- anion were synthesized and
      characterized. Their physicochemical properties, such as density, viscosity and
      ionic conductivity, electrochemical window, along with thermal properties
      including phase transition behavior and decomposition temperature, have been
      measured. All of these ILs showed large liquid range temperature, low viscosity,
      and good conductivity. Additionally, by combining DFT calculations along with
      electrochemical characterization it appears that these novel ILs show good
      electrochemical stability windows, suitable for the potential application as
      electrolyte materials in electrochemical energy storage devices.

PMID- 27717153
TI  - Agreement between adherences to four physical activity recommendations in
      patients with COPD: does the incremental shuttle walk test predict adherence?
AB  - INTRODUCTION AND OBJECTIVES: There are various recommendations for physical
      activity (PA). However agreement between all of these measures has not been
      established. Furthermore, given the challenges of measuring PA there is interest
      in evaluating whether a measure of exercise performance can be used as a
      surrogate measure to identify who is likely to achieve the recommendations.
      METHODS: A total of 184 people with COPD were recruited, 128 of which had
      complete data for these analyses. Participants wore the SenseWear Armband for 7
      consecutive days and all performed an incremental shuttle walk test (ISWT). We
      extracted moderate to vigorous physical activity (MVPA) in bouts of >=10 min
      using a 3 metabolic equivalent (MET) threshold and an individually prescribed MET
      threshold (based on performance on the ISWT). Average daily step count and the
      physical activity level were also calculated. RESULTS: There was poor agreement
      between the four PA recommendations, with agreement on all four achieved in only
      30 participants. People were least likely to be active using MVPA in >=10 min
      bouts using 3 MET threshold (21.1% active), and most likely to be active using
      MVPA in >=10 min bouts using an individually prescribed threshold (64.9% active).
      It was not possible to identify a threshold on the ISWT that would reliably
      predict those that achieved any of the four recommendations. CONCLUSION:
      Agreement between various physical activity recommendations is poor. This should
      be considered when measuring and describing physical activity adherence. The ISWT
      cannot be used to reliably predict adherence to physical activity guidelines.

PMID- 27717154
TI  - Application of testosterone to epitestosterone ratio to horse urine - a
      complementary approach to detect the administrations of testosterone and its pro
      drugs in Thoroughbred geldings.
AB  - Detection of testosterone and/or its pro-drugs in the gelding is currently
      regulated by the application of an international threshold for urinary
      testosterone of 20 ng/mL. The use of steroid ratios may provide a useful
      supplementary approach to aid in differentiating between the administration of
      these steroids and unusual physiological conditions that may result in atypically
      high testosterone concentrations. In the current study, an ultra-high performance
      liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed
      to quantify testosterone (T) and epitestosterone (E). The method was used to
      analyze 200 post-race urine samples from geldings in order to generate the ratios
      for the reference population. Following statistical analysis of the data, an
      upper limit of 5 for T:E ratio in geldings is proposed. Samples collected from 15
      geldings with atypical urinary testosterone concentrations (>15 ng/mL) but
      otherwise normal steroid profile, had T:E ratios within those observed for the
      reference population. The applicability of an upper T:E ratio to detect an
      administration was demonstrated by the analysis of a selection of incurred
      samples from testosterone propionate, dehydroepiandrosterone (DHEA), and a
      mixture of DHEA and pregnenolone (Equi-Bolic(r)) administrations. These produced
      testosterone concentrations above the threshold of 20 ng/mL, but also T:E ratios
      above the proposed limit of 5. In conclusion, consideration of the T:E ratio
      appears to be a valuable complementary aid to evaluate whether an atypical
      testosterone concentration could be caused by a natural biological outlier as
      opposed to the administration of these steroids. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27717156
TI  - Combining arterial-spin labeling with functional magnetic resonance imaging
      measurement for characterizing patients with minimal hepatic encephalopathy.
AB  - AIM: Our objective is to explore key changes in brain functions in relation to
      minimal hepatic encephalopathy (MHE). We incorporated both resting-state
      functional magnetic resonance imaging (fMRI) and arterial spin labeling (ASL) to
      enhance the detection of MHE. METHODS: We undertook fMRI scanning for 56 MHE
      patients and 66 healthy controls. Region functional connectivity was carried out
      to assess the connectivity status between pairs of regions among 90 brain
      regions. Additionally, blood flow (BF) status was measured by ASL for all
      subjects. Spearman's correlation test was implemented to identify any correlation
      among z-values, results from number connection test type A, and digit symbol
      tests. Finally, the receiver operating characteristic curve was generated for
      assessing the accuracy of BF in MHE diagnosis. RESULTS: The corresponding
      functional connectivity was significantly different between MHE and control
      groups in 15 regions. For MHE patients, BF showed an increasing pattern in
      regions of interest. Blood flood in the putamen was positively correlated with
      number connection test type A neuropsychological performance, whereas it was
      negatively correlated with the digit symbol test. Blood flood in the right
      putamen showed the highest value of area under the curve with a sensitivity of
      85.7% and specificity of 89.4%. CONCLUSION: Connectivity impairment resulting
      from ganglia-thalamo-cortical circuits may play important roles in mediating the
      development of MHE patients. An increase in the BF, particularly in the right
      putamen, may be considered as evidence for the presence of MHE.

PMID- 27717157
TI  - Inner Conflicts From a Resident Medicolegal Consulting Case.

PMID- 27717155
TI  - Genomic distribution and estimation of nucleotide diversity in natural
      populations: perspectives from the collared flycatcher (Ficedula albicollis)
      genome.
AB  - Properly estimating genetic diversity in populations of nonmodel species requires
      a basic understanding of how diversity is distributed across the genome and among
      individuals. To this end, we analysed whole-genome resequencing data from 20
      collared flycatchers (genome size ~1.1 Gb; 10.13 million single nucleotide
      polymorphisms detected). Genomewide nucleotide diversity was almost identical
      among individuals (mean = 0.00394, range = 0.00384-0.00401), but diversity levels
      varied extensively across the genome (95% confidence interval for 200-kb windows
      = 0.0013-0.0053). Diversity was related to selective constraint such that in
      comparison with intergenic DNA, diversity at fourfold degenerate sites was
      reduced to 85%, 3' UTRs to 82%, 5' UTRs to 70% and nondegenerate sites to 12%.
      There was a strong positive correlation between diversity and chromosome size,
      probably driven by a higher density of targets for selection on smaller
      chromosomes increasing the diversity-reducing effect of linked selection.
      Simulations exploring the ability of sequence data from a small number of genetic
      markers to capture the observed diversity clearly demonstrated that diversity
      estimation from finite sampling of such data is bound to be associated with large
      confidence intervals. Nevertheless, we show that precision in diversity
      estimation in large outbred population benefits from increasing the number of
      loci rather than the number of individuals. Simulations mimicking RAD sequencing
      showed that this approach gives accurate estimates of genomewide diversity. Based
      on the patterns of observed diversity and the performed simulations, we provide
      broad recommendations for how genetic diversity should be estimated in natural
      populations.

PMID- 27717159
TI  - Solubility of Organosolv Lignin in gamma-Valerolactone/Water Binary Mixtures.
AB  - The solubility of lignin in a mixture of gamma-valerolactone (GVL) and water at
      different weight ratios was measured using the Hildebrand solubility parameters.
      Based on the molecular structure of lignin, its solubility parameter (delta
      value) was calculated as 25.5 MPa1/2 . The delta-value for aqueous GVL solvent
      increased from 23.1 MPa1/2 for pure GVL to 45.6 MPa1/2 for pure water. Therefore,
      the lignin solubility was predicted to increase with increasing GVL concentration
      in the aqueous mixture up to approximately 92-96 wt % of GVL. A ternary diagram
      describing the phase behavior of water-GVL-lignin mixtures at room temperature
      was constructed based on the experimental results. The three-component system
      exhibited a complex behavior with a liquid-liquid and solid-liquid-liquid phase
      split. The efficiency of the selected fractionation trials in a previous work was
      validated using the ternary solubility diagram. A promising recovery pathway and
      lignin isolation method were deduced from the results of this work.

PMID- 27717158
TI  - Covalent Tethering and Residues with Bulky Hydrophobic Side Chains Enable Self
      Assembly of Distinct Amyloid Structures.
AB  - Polymorphism is a common property of amyloid fibers that complicates their
      detailed structural and functional studies. Here we report experiments
      illustrating the chemical principles that enable the formation of amyloid
      polymorphs with distinct stoichiometric composition. Using appropriate covalent
      tethering we programmed self-assembly of a model peptide corresponding to the [20
      41] fragment of human beta2-microglobulin into fibers with either trimeric or
      dimeric amyloid cores. Using a set of biophysical and biochemical methods we
      demonstrated their distinct structural, morphological, and templating properties.
      Furthermore, we showed that supramolecular approaches in which the peptide is
      modified with bulky substituents can also be applied to modulate the formation of
      different fiber polymorphs. Such strategies, when applied to disease-related
      peptides and proteins, will greatly help in the evaluation of the biological
      properties of structurally distinct amyloids.

PMID- 27717161
TI  - The problem Of muscle hypertrophy: Revisited.
AB  - In this paper we revisit a topic originally discussed in 1955, namely the lack of
      direct evidence that muscle hypertrophy from exercise plays an important role in
      increasing strength. To this day, long-term adaptations in strength are thought
      to be primarily contingent on changes in muscle size. Given this assumption,
      there has been considerable attention placed on programs designed to allow for
      maximization of both muscle size and strength. However, the conclusion that a
      change in muscle size affects a change in strength is surprisingly based on
      little evidence. We suggest that these changes may be completely separate
      phenomena based on: (1) the weak correlation between the change in muscle size
      and the change in muscle strength after training; (2) the loss of muscle mass
      with detraining, yet a maintenance of muscle strength; and (3) the similar muscle
      growth between low-load and high-load resistance training, yet divergent results
      in strength. Muscle Nerve 54: 1012-1014, 2016.

PMID- 27717160
TI  - Water Oxidation by Size-Selected Co27 Clusters Supported on Fe2 O3.
AB  - The complexity of the water oxidation reaction makes understanding the role of
      individual catalytic sites critical to improving the process. Here, size-selected
      27-atom cobalt clusters (Co27 ) deposited on hematite (Fe2 O3 ) anodes were
      tested for water oxidation activity. The uniformity of these anodes allows
      measurement of the activity of catalytic sites of well-defined nuclearity and
      known density. Grazing incidence X-ray absorption near-edge spectroscopy
      (GIXANES) characterization of the anodes before and after electrochemical cycling
      demonstrates that these Co27 clusters are stable to dissolution even in the harsh
      water oxidation electrochemical environment. They are also stable under
      illumination at the equivalent of 0.4 suns irradiation. The clusters show
      turnover rates for water oxidation that are comparable or higher than those
      reported for Pd- and Co-based materials or for hematite. The support for the Co27
      clusters is Fe2 O3 grown by atomic layer deposition on a Si chip. We have chosen
      to deposit a Fe2 O3 layer that is only a few unit cells thick (2 nm), to remove
      complications related to exciton diffusion. We find that the electrocatalytic and
      the photoelectrocatalytic activity of the Co27 /Fe2 O3 material is significantly
      improved when the samples are annealed (with the clusters already deposited).
      Given that the support is thin and that the cluster deposition density is
      equivalent to approximately 5 % of an atomic monolayer, we suggest that annealing
      may significantly improve the exciton diffusion from the support to the catalytic
      moiety.

PMID- 27717162
TI  - Embryonic hypocellularity, blastogenetic malformations, and fetal growth
      restriction.
AB  - An association between congenital malformations and fetal growth restriction
      (FGR) can be largely explained by a relationship with early embryonic
      hypocellularity. The malformations include the VACTERL association, which is
      exceptional as a Mendelian syndrome, but is commonly associated with monozygotic
      twinning, maternal diabetes, and some forms of aneuploidy, all characterized by a
      small embryo early in development. Parsimony suggests that these different links
      to VACTERL are related to the hypocellularity as a single common factor, rather
      than as an expression of three independent pathogenetic processes. A distinct non
      genetic pathogenesis is further supported by increased frequencies in the same
      conditions of a single umbilical artery (SUA), which is also unusual in Mendelian
      disorders. SUA often involves the atrophy of one artery, which may be facilitated
      by altered hemodynamics in a smaller embryo, providing a direct link to
      hypocellularity. Hypocellularity may also explain a possible connection between
      VACTERL and certain mitochondrial disorders, where reduced energy might slow
      early cell division and growth, reducing the size of the embryo. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27717164
TI  - No effect of Bt-transgenic rice litter on the meiobenthos community in field
      ditches.
AB  - BACKGROUND: The non-target effect of Bacillus thuringiensis (Bt) toxins in
      aquatic ecosystems is crucial to improve the present assessment of Bt-transgenic
      plants, particularly where crops are cultivated near aquatic ecosystems. We
      conducted decomposition experiments during two growing seasons to determine the
      effects of Bt-transgenic rice litter with and without insecticide application on
      the meiobenthos communities in a field ditch. RESULTS: The community composition
      of meiobenthos colonised on leaf litter was not significantly different between
      Bt and non-Bt rice. The abundance of meiobenthos colonising leaves differed
      between insecticide application and control, and this insecticide effect
      interacted with rice type. No Bt toxin was detected in field ditch water. Leaf
      decomposition and nutrient content were comparable for both Bt and non-Bt rice
      with or without insecticide application. CONCLUSION: Bt-transgenic rice litter
      had no effect on the meiobenthos community composition in field ditches, but the
      chronic persistence of transgenic litter in nature needs to be taken into account
      at large scales in aquatic ecosystems. (c) 2016 Society of Chemical Industry.

PMID- 27717163
TI  - Mucus-Penetrating Nanosuspensions for Enhanced Delivery of Poorly Soluble Drugs
      to Mucosal Surfaces.
AB  - Mucus-penetrating nanosuspensions, consisting of pure hydrophobic therapeutics
      with dense muco-inert coatings that enable particles to effectively bypass the
      mucus barrier, demonstrate superior drug distribution and absorption at mucosal
      surfaces. With significantly increased drug load compared to polymeric systems
      and established clinical translation of nanosuspensions-based products, mucus
      penetrating nanosuspensions are a promising vehicle for improving mucosal
      delivery of poorly soluble drugs.

PMID- 27717165
TI  - Preoperative direct bilirubin to prothrombin time ratio index to prevent liver
      failure after minor hepatectomy.
AB  - BACKGROUND: The most reliable index to predict the safety of hepatectomy for
      patients with poor liver function remains unknown. We aimed to construct a novel
      preoperative index to predict early liver failure (ELF) and mortality due to
      recurrence-free liver failure (MLF) after hepatectomy. METHODS: Between 2000 and
      2012, 385 consecutive patients with hepatocellular carcinoma undergoing curative
      minor hepatectomy were divided into two sequential cohorts: training set (n =
      143) and validation set (n = 242), and observed until 2015. RESULTS: Prothrombin
      time and direct bilirubin were independent predictors of both ELF and MLF in the
      training set. Thus we devised a novel index, the direct bilirubin to prothrombin
      time ratio index (DBPTRI). The areas under ROC curves of DBPTRI for predicting
      ELF and MLF were 0.78 and 0.93, respectively, in the validation set. Using a
      preoperative DBPTRI cut off of 4.2, we accurately predicted ELF and MLF in 86.8%
      and 88.4% of patients, respectively. DBPTRI was the best predictor of ELF and MLF
      when compared with conventional indices such as ICG-R15 and Child-Pugh score.
      Moreover, the 5-year overall survival rates of the patients with low and high
      DBPTRI were 59% and 36%, respectively (P < 0.0001). CONCLUSIONS: DBPTRI may serve
      as a simple, non-invasive index for estimating liver failure after hepatectomy.

PMID- 27717166
TI  - Mechanism for odd-electron anion generation of dihydroxybenzoic acid isomers in
      matrix-assisted laser desorption/ionization mass spectrometry with density
      functional theory calculations.
AB  - RATIONALE: Proton and radical are transferred between matrices and matrix and
      analyte in matrix-assisted laser desorption/ionization (MALDI) and these
      transfers drive ionization of analytes. The odd-electron anion [M-2H]*- was
      generated in dihydroxybenzoic acids (DHBs) and the ion abundance of the 2,5-DHB
      was the highest among six DHB isomers. We were interested in the mechanism of the
      ion generation of the odd-electron anion. METHODS: The observed [M-2H]*- and [M
      3H]- ions, which were generated with the hydrogen radical removed from the
      phenolic hydroxyl groups (OH) in DHB isomers, were analyzed using negative-ion
      MALDI-MS. The enthalpy for ion generation and their stable structures were
      calculated using the density functional theory (DFT) calculation program Gaussian
      09 with the B3LYP functional and the 6-31+G(d) basis set. RESULTS: The number of
      observed [M-2H]*- and [M-3H]- ions of the DHB isomers was dependent on the
      positions of the phenolic OH groups in the DHB isomers because the carboxy group
      interacts with the ortho OH group due to neighboring group participation, as
      confirmed from the stable structures of the [M-2H]*- anions calculated with the
      Gaussian 09 program. The DHB isomers were placed into three categories according
      to the number of the ions. CONCLUSIONS: Odd-electron anions ([M-2H]*- ) and [M
      2H* -H]- ([M-3H]- ) ions were generated from DHB isomers due to removal of the
      hydrogen radical from the phenolic groups. The enthalpy for ion generation
      revealed that ion formation proceeds via a two-step pathway through the [M-M]-
      ion as an intermediate. (c) 2016 The Authors. Rapid Communications in Mass
      Spectrometry Published by John Wiley & Sons Ltd.

PMID- 27717167
TI  - Dynamic Responsive Systems for Catalytic Function.
AB  - Responsive systems have recently gained much interest in the scientific community
      in attempts to mimic dynamic functions in biological systems. One of the
      fascinating potential applications of responsive systems lies in catalysis.
      Inspired by nature, novel responsive catalytic systems have been built that show
      analogy with allosteric regulation of enzymes. The design of responsive catalytic
      systems allows control of catalytic activity and selectivity. In this Review,
      advances in the field over the last four decades are discussed and a comparison
      is made amongst the dynamic responsive systems based on the principles underlying
      their catalytic mechanisms. The catalyst systems are sorted according to the
      triggers used to achieve control of the catalytic activity and the distinct
      catalytic reactions illustrated.

PMID- 27717168
TI  - Beneficial Role of Reduced Graphene Oxide for Electron Extraction in Highly
      Efficient Perovskite Solar Cells.
AB  - In this work we systematically investigated the role of reduced graphene oxide
      (rGO) in hybrid perovskite solar cells (PSCs). By mixing rGO within the
      mesoporous TiO2 (m-TiO2 ) matrix, highly efficient solar cells with power
      conversion efficiency values up to 19.54 % were realized. In addition, the
      boosted beneficial role of rGO with and without Li-treated m-TiO2 is highlighted,
      improving transport and injection of photoexcited electrons. This combined system
      may pave the way for further development and optimization of electron transport
      and collection in high efficiency PSCs.

PMID- 27717170
TI  - Changes in the rumen microbiome and metabolites reveal the effect of host
      genetics on hybrid crosses.
AB  - The rumen microbiota plays important roles in nutrient metabolism and absorption
      of the host. However, it is poorly understood how host genetic variation shapes
      the community structure of the rumen microbiota and its metabolic phenotype.
      Here, we used sika deer (Cervus nippon) and elk (Cervus elaphus) to produce the
      following two types of hybrid offspring: sika deer ? * elk ? (SEH) and elk ? *
      sika deer ? (ESH). Then, we examined the rumen microbiome and metabolites in the
      parents and their hybrid offspring. The rumen microbiota in the hybrids differed
      from that in their parents, suggesting a significant effect of host genetics on
      the rumen microbiome that may have resulted from vertical transmission. The rumen
      metabolites displayed patterns similar to the structure of the rumen microbiome,
      with changes in the amounts of volatile fatty acids and metabolites of amino
      acids. The alanine, arginine, proline and phenylalanine pathways were enriched in
      the rumen of hybrid animals. The enriched metabolites in the above pathways were
      positively correlated with the bacteria Prevotella spp., Acetitomaculum spp.,
      Quinella spp., Succinivibrio spp. and Ruminobacter spp. These results suggest
      that host genetics has a major impact on the rumen microbiome and metabolites in
      hybrid animals.

PMID- 27717169
TI  - 5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in
      BTBR mice.
AB  - Restricted and repetitive behaviors are a defining feature of autism, which can
      be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors.
      There is limited knowledge about the underlying neuropathophysiology contributing
      to these behaviors. Previous findings suggest that central 5HT2A receptor
      activity is altered in autism, while recent work indicates that systemic 5HT2A
      receptor antagonist treatment reduces repetitive behaviors in an idiopathic model
      of autism. 5HT2A receptors are expressed in the orbitofrontal cortex and
      striatum. These two regions have been shown to be altered in autism. The present
      study investigated whether 5HT2A receptor blockade in the dorsomedial striatum or
      orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism,
      affects the phenotype related to restricted and repetitive behaviors.
      Microinfusion of the 5HT2A receptor antagonist, M100907 into the dorsomedial
      striatum alleviated a reversal learning impairment and attenuated grooming
      behavior. M100907 infusion into the orbitofrontal cortex increased perseveration
      during reversal learning and potentiated grooming. These findings suggest that
      increased 5HT2A receptor activity in the dorsomedial striatum may contribute to
      behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT2A
      receptor signaling in the orbitofrontal cortex may be critical for inhibiting a
      previously learned response during reversal learning and expression of
      stereotyped behavior. The present results suggest which brain areas exhibit
      abnormalities underlying repetitive behaviors in an idiopathic mouse model of
      autism, as well as which brain areas systemic treatment with M100907 may
      principally act on in BTBR mice to attenuate repetitive behaviors.

PMID- 27717171
TI  - Light quality and quantity regulate aerobic methane emissions from plants.
AB  - Studies have been mounting in support of the finding that plants release aerobic
      methane (CH4 ), and that these emissions are increased by both short-term and
      long-term environmental stress. It remains unknown whether or not they are
      affected by variation in light quantity and quality, whether emissions change
      over time, and whether they are influenced by physiological parameters. Light is
      the primary energy source of plants, and therefore an important regulator of
      plant growth and development. Both shade-intolerant sunflower and shade-tolerant
      chrysanthemum were investigated for the release of aerobic CH4 emissions, using
      either low or high light intensity, and varying light quality, including control,
      low or normal red:far-red ratio (R:FR), and low or high levels of blue, to
      discern the relationship between light and CH4 emissions. It was found that low
      levels of light act as an environmental stress, facilitating CH4 release from
      both species. R:FR and blue lights increased emissions under low light, but the
      results varied with species, providing evidence that both light quantity and
      quality regulate CH4 emissions. Emission rates of 6.79-41.13 ng g-1 DW h-1 and
      18.53-180.25 ng g-1 DW h-1 were observed for sunflower and chrysanthemum,
      respectively. Moreover, emissions decreased with age as plants acclimated to
      environmental conditions. Since effects were similar in both species, there may
      be a common trend among a number of shade-tolerant and shade-intolerant species.
      Light quantity and quality are influenced by factors including cloud covering, so
      it is important to know how plants will be affected in the context of aerobic CH4
      emissions.

PMID- 27717172
TI  - Comparative genomics and physiology of the butyrate-producing bacterium
      Intestinimonas butyriciproducens.
AB  - Intestinimonas is a newly described bacterial genus with representative strains
      present in the intestinal tract of human and other animals. Despite unique
      metabolic features including the production of butyrate from both sugars and
      amino acids, there is to date no data on their diversity, ecology, and
      physiology. Using a comprehensive phylogenetic approach, Intestinimomas was found
      to include at least three species that colonize primarily the human and mouse
      intestine. We focused on the most common and cultivable species of the genus,
      Intestinimonas butyriciproducens, and performed detailed genomic and
      physiological comparison of strains SRB521T and AF211, isolated from the mouse
      and human gut respectively. The complete 3.3-Mb genomic sequences of both strains
      were highly similar with 98.8% average nucleotide identity, testifying to their
      assignment to one single species. However, thorough analysis revealed significant
      genomic rearrangements, variations in phage-derived sequences, and the presence
      of new CRISPR sequences in both strains. Moreover, strain AF211 appeared to be
      more efficient than strain SRB521T in the conversion of the sugars arabinose and
      galactose. In conclusion, this study provides genomic and physiological insight
      into Intestinimonas butyriciproducens, a prevalent butyrate-producing species,
      differentiating strains that originate from the mouse and human gut.

PMID- 27717173
TI  - Metal/Graphitic Carbon Nitride Composites: Synthesis, Structures, and
      Applications.
AB  - Graphitic carbon nitride (g-C3 N4 ) has been widely used in fields related to
      energy and materials science. However, nanostructured g-C3 N4 photocatalysts
      synthesized by traditional thermal polycondensation methods have the disadvantage
      of small specific surface areas and wide band gaps; these limit the catalytic
      activity and application range of g-C3 N4 . Based on the unique nanostructure of
      g-C3 N4 , it is a feasible method to modify g-C3 N4 with metals to design novel
      metal-semiconductor composites. Metals alter the photochemical properties of g-C3
      N4 , in particular, narrow the band gap and expand photoabsorption into the
      visible range, which improves the photocatalytic performance. This review covers
      recent progress in metal/g-C3 N4 nanocomposites for photocatalysts, organic
      systems, biosensors, and so on. The aim is to summarize the synthetic methods,
      nanostructures, and applications of metal/g-C3 N4 nanocomposite materials, as
      well as discuss future research directions in these areas.

PMID- 27717175
TI  - Abstracts from the 2016 ISDE World Congress.

PMID- 27717174
TI  - Bioinspired Superhydrophobic Highly Transmissive Films for Optical Applications.
AB  - Inspired by the transparent hair layer on water plants Salvinia and Pistia,
      superhydrophobic flexible thin films, applicable as transparent coatings for
      optoelectronic devices, are introduced. Thin polymeric nanofur films are
      fabricated using a highly scalable hot pulling technique, in which heated
      sandblasted steel plates are used to create a dense layer of nano- and microhairs
      surrounding microcavities on a polymer surface. The superhydrophobic nanofur
      surface exhibits water contact angles of 166 +/- 6 degrees , sliding angles below
      6 degrees , and is self-cleaning against various contaminants. Additionally,
      subjecting thin nanofur to argon plasma reverses its surface wettability to
      hydrophilic and underwater superoleophobic. Thin nanofur films are transparent
      and demonstrate reflection values of less than 4% for wavelengths ranging from
      300 to 800 nm when attached to a polymer substrate. Moreover, used as translucent
      self-standing film, the nanofur exhibits transmission values above 85% and high
      forward scattering. The potential of thin nanofur films for extracting substrate
      modes from organic light emitting diodes is tested and a relative increase of the
      luminous efficacy of above 10% is observed. Finally, thin nanofur is optically
      coupled to a multicrystalline silicon solar cell, resulting in a relative gain of
      5.8% in photogenerated current compared to a bare photovoltaic device.

PMID- 27717177
TI  - Nanostructured Bifunctional Redox Electrocatalysts.
AB  - Electrocatalysts are playing a prominent role in the design of renewable energy
      devices. Benefiting from a long and prosperous history of synthesizing individual
      hydrogen evolution reaction (HER), oxygen evolution reaction (OER) and oxygen
      reduction reaction (ORR) electrocatalysts, the development of bifunctional
      ORR/OER or HER/OER electrocatalysts has recently emerged as a new research
      hotspot. In this review, a brief account of recent developments of bifunctional
      electrocatalysts for ORR/OER and HER/OER are introduced, aiming to provide
      insights into theoretical understanding of these reactions through analysis and
      comparison of various bifunctional electrocatalysts. The related reaction
      mechanisms and the associated activity descriptors for aforementioned reactions
      in the recent literatures are also presented. Different series of bifunctional
      electrocatalysts with much improved performances are discussed in detail and
      their design principles are outlined. Finally, the existing challenges and the
      future effort directions for enhancing the performance of bifunctional
      electrocatalysts are proposed.

PMID- 27717178
TI  - Biological control potential of entomopathogenic nematodes for management of
      Caribbean fruit fly, Anastrepha suspensa Loew (Tephritidae).
AB  - BACKGROUND: Caribbean fruit fly (Caribfly) is a serious economic insect pest
      because of development of larvae that hatch from eggs oviposited into fruits by
      female adults. This study assessed the virulence of twelve entomopathogenic
      nematode (EPN) isolates to Caribfly in laboratory bioassays as a starting point
      toward evaluation of management strategies for the fruit-to-soil-dwelling stages
      of A. suspensa in fields infested by Caribfly. RESULTS: Inoculation of A.
      suspensa with 1 mL of ca 200 IJs larva-1 killed Caribfly at either larval or
      pupal stage. Pupae were more resistant to EPN infections than larvae. Adult
      emergence from inoculated pupae in soil microcosms was significantly lower than
      that observed in filter paper assays. Longest or largest steinernematids
      suppressed emergence of more adult Caribfly from pupae in soils, whereas shorter
      heterorhabditids were more infectious to Caribfly larvae. The highest mortalities
      of A. suspensa were caused by exotic nematodes Steinernema feltiae and
      Heterorhabditis bacteriophora, followed by the native Heterorhabditis indica and
      the exotic Steinernema carpocapsae. CONCLUSION: Entomopathogenic nematodes
      reduced the development of Caribfly larvae and pupae to adult in our bioassays,
      suggesting that EPNs have potential for biological control of A. suspensa. Future
      work will assess management strategies, using the virulent EPNs, in orchards
      infested by A. suspensa. (c) 2016 Society of Chemical Industry.

PMID- 27717176
TI  - Local Delivery of PHD2 siRNA from ROS-Degradable Scaffolds to Promote Diabetic
      Wound Healing.
AB  - Small interfering RNA (siRNA) delivered from reactive oxygen species-degradable
      tissue engineering scaffolds promotes diabetic wound healing in rats. Porous
      poly(thioketal-urethane) scaffolds implanted in diabetic wounds locally deliver
      siRNA that inhibits the expression of prolyl hydroxylase domain protein 2,
      thereby increasing the expression of progrowth genes and increasing vasculature,
      proliferating cells, and tissue development in diabetic wounds.

PMID- 27717179
TI  - Theoretical Investigation and Design of Highly Efficient Blue Phosphorescent
      Iridium(III) Complexes Bearing Fluorinated Aromatic Sulfonyl Groups.
AB  - Aromatic sulfonyl groups have attracted increasing interest due to their unique
      electronic features. In this article, a series of IrIII complexes bearing
      fluorinated phenylsulfonyl groups were evaluated by density functional theory and
      time-dependent density functional theory methods. To explore their
      phosphorescence efficiencies, factors that determine the radiative decay rate
      constant, kr , and the nonradiative decay rate constant, knr , were computed. As
      demonstrated by the results, complex 4, which has fluorinated phenylsulfonyl
      groups at the 5-positions of the phenyl rings for all three C^N ligands, was
      found to have the highest phosphorescence efficiencies with the largest kr and
      smallest knr values among these complexes. Moreover, it was found to exhibit
      significantly blueshifted behavior relative to complex 1 and emits in the blue
      region, and thus, it can serve as a highly efficient blue emitter for application
      in organic light-emitting diodes. These findings successfully illustrated the
      structure-properties relationship and provided valuable information for the
      development of future highly efficient blue-emitting phosphors.

PMID- 27717180
TI  - Does obesity influence the subgingival microbiota composition in periodontal
      health and disease?
AB  - AIM: To evaluate whether obesity affects the subgingival microbial composition of
      patients with periodontal health or chronic periodontitis (CP). MATERIALS AND
      METHODS: Based on periodontal parameters, body mass index and waist-hip ratio,
      166 patients were allocated into one of the following groups: Normal weight (NW)
      patients with periodontal health (n = 44), NW patients with CP (n = 40), obese
      patients with periodontal health (n = 40) and obese patients with CP (n = 42).
      Six subgingival biofilm samples per patient were analysed for their content of 40
      bacterial species using checkerboard DNA-DNA hybridization. RESULTS: Obese
      patients with CP harboured higher levels and/or higher proportions of several
      periodontal pathogens than those with NW and CP, including Aggregatibacter
      actinomycetemcomitans, Eubacterium nodatum, Fusobacterium nucleatum ss vincentii,
      Parvimonas micra, Prevotella intermedia, Tannerella forsythia, Prevotella
      melaninogenica and Treponema socranskii. The proportions of most of these
      pathogens, as well Campylobacter rectus and Eikenella corrodens, were more
      increased in the diseased sites of the obese patients than in those with NW.
      Furthermore, the healthy sites of the obese patients, presenting or not CP, also
      exhibited higher proportions of some of the pathogens than patients with NW.
      CONCLUSIONS: Obesity is associated with increased levels and proportions of
      periodontal pathogens, especially in patients with CP.

PMID- 27717181
TI  - New Generation of Tunable Bioactive Shape Memory Mats Integrated with Genetically
      Engineered Proteins.
AB  - Aligned poly(l-lactide)/poly(methyl methacrylate) binary blend fibers and mats
      loaded with a chimeric green fluorescence protein having a bioactive peptide with
      hydroxyapatite binding and mineralization property are prepared by pressurized
      gyration. The effect of processing parameters on the product morphologies, and
      the shape memory properties of these samples are investigated. Integration of
      hydroxyapatite nanoparticles into the fiber assembly is self-directed using the
      hydroxyapatite-binding property of the peptide genetically engineered to green
      fluorescence protein. Fluorescence microscopy analysis corroborated with Fourier
      transform infrared spectroscopy (FTIR) data confirms the integration of the
      chimeric protein with the fibers. An enzyme based remineralization assay is
      conducted to study the effects of peptide-mediated mineralization within the
      fiber mats. Raman and FTIR spectral changes observed following the peptide
      mediated mineralization provides an initial step toward a soft-hard material
      transition. These results show that programmable shape memory properties can be
      obtained by incorporating genetically engineered bioactive peptide domains into
      polymer fibers.

PMID- 27717182
TI  - Atg1-independent induction of autophagy by the Drosophila Ulk3 homolog, ADUK.
AB  - Although canonical autophagy regulation requires a multi-protein complex centered
      on the Ser/Thr-kinase Atg1 (mammalian Ulk1/2), alternative signals can induce
      autophagy independent of Atg1 through unknown mechanisms. Here we identify the
      Drosophila Ulk3 ortholog, another Drosophila Unc-51-like kinase (ADUK), as an
      Atg1-independent autophagy inducer. ADUK interacts with Atg1 complex members
      Atg13 and 200 kDa FAK family kinase-interacting protein, and requires Atg13 but
      not Atg1 for autophagy induction. Loss of ADUK shortens adult lifespan and
      reduces the autophagic response to a chemical stressor, dimethyl sulfoxide.
      However, ADUK is not required for autophagy induction by Atg1-dependent nutrient
      or developmental cues. Atg1 and ADUK/Ulk3 thus represent alternative catalytic
      components of a shared autophagy kinase complex.

PMID- 27717183
TI  - Design, synthesis, and biological evaluation of novel tetrahydroisoquinoline
      derivatives as potential antitumor candidate.
AB  - A novel class of tetrahydroisoquinoline derivatives was designed and synthesized
      as antitumor agents and evaluated for their in vitro and in vivo biological
      activities. The antiproliferative activities of all the target compounds on
      HUVEC, MCF-7, and HT-29 were evaluated. Compared with colchicine (1.04 * 10-2 
      MUm), 17d and 17e exhibited outstanding activity on MCF-7 with IC50 values 0.26 *
      10-2  MUm and 0.89 * 10-3 MUm in cell cytotoxicity assay. The tubulin
      polymerization assay demonstrated that 17d and 17e exhibited better inhibition
      rate. In the MCF-7-xenograft mouse model that was treated with 17d and 17e by
      intraperitoneal injection, the tumor weight was decreased at same rate with
      tamoxifen, and relative tumor proliferation rates were 59.48% and 41.33%, while
      tamoxifen was 45.08% with a daily dose of 20 mg/kg, which were demonstrated
      potent in vivo efficacy.

PMID- 27717185
TI  - Ultrasonic Cavitation Induced Shape-Memory Effect in Porous Polymer Networks.
AB  - Inspired by the application of ultrasonic cavitation based mechanical force (CMF)
      to open small channels in natural soft materials (skin or tissue), it is explored
      whether an artificial polymer network can be created, in which shape-changes can
      be induced by CMF. This concept comprises an interconnected macroporous rhodium
      phosphine (Rh-P) coordination polymer network, in which a CMF can reversibly
      dissociate the Rh-P microphases. In this way, the ligand exchange of Rh-P
      coordination bonds in the polymer network is accelerated, resulting in a
      topological rearrangement of molecular switches. This rearrangement of molecular
      switches enables the polymer network to release internal tension under ultrasound
      exposure, resulting in a CMF-induced shape-memory capability. The interconnected
      macroporous structure with thin pore walls is essential for allowing the CMF to
      effectively permeate throughout the polymer network. Potential applications of
      this CMF-induced shape-memory polymer can be mechanosensors or ultrasound
      controlled switches.

PMID- 27717184
TI  - Nuclear phosphoproteome analysis of 3T3-L1 preadipocyte differentiation reveals
      system-wide phosphorylation of transcriptional regulators.
AB  - Adipocytes (fat cells) are important endocrine and metabolic cells critical for
      systemic insulin sensitivity. Both adipose excess and insufficiency are
      associated with adverse metabolic function. Adipogenesis is the process whereby
      preadipocyte precursor cells differentiate into lipid-laden mature adipocytes.
      This process is driven by a network of transcriptional regulators (TRs). We
      hypothesized that protein PTMs, in particular phosphorylation, play a major role
      in activating and propagating signals within TR networks upon induction of
      adipogenesis by extracellular stimulus. We applied MS-based quantitative
      proteomics and phosphoproteomics to monitor the alteration of nuclear proteins
      during the early stages (4 h) of preadipocyte differentiation. We identified a
      total of 4072 proteins including 2434 phosphorylated proteins, a majority of
      which were assigned as regulators of gene expression. Our results demonstrate
      that adipogenic stimuli increase the nuclear abundance and/or the phosphorylation
      levels of proteins involved in gene expression, cell organization, and oxidation
      reduction pathways. Furthermore, proteins acting as negative modulators involved
      in negative regulation of gene expression, insulin stimulated glucose uptake, and
      cytoskeletal organization showed a decrease in their nuclear abundance and/or
      phosphorylation levels during the first 4 h of adipogenesis. Among 288 identified
      TRs, 49 were regulated within 4 h of adipogenic stimulation including several
      known and many novel potential adipogenic regulators. We created a kinase
      substrate database for 3T3-L1 preadipocytes by investigating the relationship
      between protein kinases and protein phosphorylation sites identified in our
      dataset. A majority of the putative protein kinases belong to the cyclin
      dependent kinase family and the mitogen-activated protein kinase family including
      P38 and c-Jun N-terminal kinases, suggesting that these kinases act as
      orchestrators of early adipogenesis.

PMID- 27717187
TI  - Feasibility of squeezing multiple breath washout testing into busy clinical
      laboratories.

PMID- 27717186
TI  - Anesthesia reduces discharge rates in the human pallidum without changing the
      discharge rate ratio between pallidal segments.
AB  - Classical rate models of basal ganglia circuitry associate discharge rate of the
      globus pallidus external and internal segments (GPe, GPi respectively) solely
      with dopaminergic state and predict an inverse ratio between the discharge rates
      of the two pallidal segments. In contrast, the effects of other rate modulators
      such as general anesthesia (GA) on this ratio have been ignored. To respond to
      this need, we recorded the neuronal activity in the GPe and GPi in awake and
      anesthetized human patients with dystonia (57 and 53 trajectories respectively)
      and in awake patients with Parkinson's disease (PD, 16 trajectories) undergoing
      deep brain stimulation procedures. This triad enabled us to dissociate pallidal
      discharge ratio from general discharge modulation. An automatic offline spike
      detection and isolation quality system was used to select 1560 highly isolated
      units for analysis. The mean discharge rate in the GPi of awake PD patients was
      dramatically higher than in awake dystonia patients although the firing rate in
      the GPe was similar. Firing rates in dystonic patients under anesthesia were
      lower in both nuclei. Surprisingly, in all three groups, GPe firing rates were
      correlated with firing rates in the ipsilateral GPi. Thus, the firing rate ratio
      of ipsilateral GPi/GPe pairs was similar in awake and anesthetized patients with
      dystonia and significantly higher in PD. We suggest that pallidal activity is
      modulated by at least two independent processes: dopaminergic state which changes
      the GPi/GPe firing rate ratio, and anesthesia which modulates firing rates in
      both pallidal nuclei without changing the ratio between their firing rates.

PMID- 27717188
TI  - Preliminary Investigation of Cardiovascular-Renal Disorders in Dogs with Chronic
      Mitral Valve Disease.
AB  - BACKGROUND: Veterinary literature lacks data about cardiovascular-renal disorders
      (CvRD) and cardiorenal-anemia syndrome (CRAS) in dogs. HYPOTHESIS: A direct
      correlation exists between ACVIM class and IRIS stage; chronic kidney disease
      (CKD) complicates chronic mitral valve disease (CMVD) more often than does anemia
      in dogs. ANIMALS: One hundred and fifty-eight client-owned dogs with CMVD.
      METHODS: Signalment, physical examination findings, electrocardiography, thoracic
      radiographs, echocardiography, and blood analysis were retrospectively evaluated
      to assess the prevalence of CKD and anemia in dogs with CMVD and to investigate
      the relationships among ACVIM class, IRIS stage, and survival. RESULTS: The
      prevalence of CKD and anemia in dogs with CMVD was significantly higher than in
      the general population of dogs. Dogs being treated for heart failure had a
      significantly higher prevalence of CKD than did dogs that had not received
      treatment. A statistically significant direct correlation was found between ACVIM
      class and IRIS stage. Severe heart disease, severe renal disease or both,
      furosemide administration, and advanced age at diagnosis of heart disease were
      associated with shorter survival time. Survival time of dogs affected by CvRD was
      statistically shorter than survival time of dogs affected by CMVD alone.
      CONCLUSION AND CLINICAL RELEVANCE: Chronic mitral valve disease is associated
      with increased prevalence of CKD and anemia in dogs. Treatment for medical
      management of heart failure may play a role in inducing CKD. Class of heart
      disease and IRIS stage were directly correlated. Cardiovascular-renal disorders
      decrease survival time compared to the only presence of CMVD alone, whereas
      anemia does not play a central role in worsening heart function.

PMID- 27717191
TI  - Clinicopathologic and Histopathologic Renal Abnormalities in Dogs with
      Coccidioidomycosis.
AB  - BACKGROUND: We observed evidence of protein-losing nephropathy in some dogs with
      coccidioidomycosis, suggestive of immune complex glomerulonephritis (ICGN). The
      goal of this study was to understand the prevalence of renal histopathologic
      lesions and proteinuria in dogs with coccidioidomycosis. HYPOTHESIS: Biochemical
      and histopathological evidence of glomerular lesions is present in dogs with
      coccidioidomycosis. ANIMALS: Hundred and fifty-six dogs with naturally occurring
      coccidioidomycosis. METHODS: Retrospective case series. Clinical information and
      results of clinicopathologic testing were retrieved from the University of
      California, Davis Veterinary Medical Teaching Hospital (VMTH). Microscopic
      sections of renal tissue procured from necropsy of dogs with coccidioidomycosis
      were examined to evaluate the nature and distribution of lesions. RESULTS: A
      total of 156 dogs with coccidioidomycosis were identified; 87 dogs had serum
      biochemistry and a urinalysis performed, 17 had urine protein:creatinine ratios
      (UPCs), and 24 had renal tissue available for histopathology. Eleven (13%) of the
      87 dogs were azotemic, 55 (63%) were proteinuric (of which 14 [25%] had
      clinically relevant proteinuria defined as >=3+ or >=500 mg/dL), and 14 dogs had
      UPC >=0.5 (range, 0.5-21.5, median 4.2). Thirteen (54%) of 24 dogs had renal
      histopathologic lesions suggestive of ICGN. Seven of these dogs had urinalyses
      performed; 5 (71%) had clinically relevant proteinuria as described above. Two
      dogs (33%) with normal glomeruli had granulomatous nephritis, 1 of which had
      intralesional Coccidioides spherules. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Coccidioidomycosis should be considered as a possible contributor to glomerular
      disease in dogs. Whether similar lesions occur in other mammalian hosts,
      including humans, warrants further investigation.

PMID- 27717189
TI  - Degenerative Encephalopathy in Nova Scotia Duck Tolling Retrievers Presenting
      with a Rapid Eye Movement Sleep Behavior Disorder.
AB  - BACKGROUND: Neurodegenerative diseases are a heterogeneous group of disorders
      characterized by loss of neurons and are commonly associated with a genetic
      mutation. HYPOTHESIS/OBJECTIVES: To characterize the clinical and
      histopathological features of a novel degenerative neurological disease affecting
      the brain of young adult Nova Scotia Duck Tolling Retrievers (NSDTRs). ANIMALS:
      Nine, young adult, related NSDTRs were evaluated for neurological dysfunction and
      rapid eye movement sleep behavior disorder. METHODS: Case series review. RESULTS:
      Clinical signs of neurological dysfunction began between 2 months and 5 years of
      age and were progressive in nature. They were characterized by episodes of marked
      movements during sleep, increased anxiety, noise phobia, and gait abnormalities.
      Magnetic resonance imaging documented symmetrical, progressively increasing, T2
      weighted image intensity, predominantly within the caudate nuclei, consistent
      with necrosis secondary to gray matter degeneration. Abnormalities were not
      detected on clinicopathological analysis of blood and cerebrospinal fluid,
      infectious disease screening or urine metabolite screening in most cases.
      Postmortem examination of brain tissue identified symmetrical malacia of the
      caudate nuclei and axonal dystrophy within the brainstem and spinal cord.
      Genealogical analysis supports an autosomal recessive mode of inheritance.
      CONCLUSIONS AND CLINICAL IMPORTANCE: A degenerative encephalopathy was identified
      in young adult NSDTRs consistent with a hereditary disease. The prognosis is
      guarded due to the progressive nature of the disease, which is minimally
      responsive to empirical treatment.

PMID- 27717190
TI  - Factors Influencing the Relationship Between the Dose of Amlodipine Required for
      Blood Pressure Control and Change in Blood Pressure in Hypertensive Cats.
AB  - BACKGROUND: Hypertension is a common problem in elderly cats. In most cats,
      systolic blood pressure (SBP) of <160 mmHg is achieved in response to amlodipine
      besylate at either 0.625 or 1.25 mg q24h. The individual cat factors determining
      dose requirement dose have not been explored. AIMS: To determine whether
      individual cat factors influence the dose of amlodipine required to achieve
      adequate blood pressure control and to determine whether factors other than the
      prescribed dose of drug alter the achieved plasma amlodipine concentrations.
      METHODS: Fifty-nine hypertensive cats that required 0.625 mg (A) and 41 cats that
      required 1.25 mg (B) amlodipine to reach a target SBP of <160 mmHg were
      identified, and plasma amlodipine concentrations were determined. Comparisons
      were made between groups, and multivariable linear regression models were
      performed to investigate predictors of antihypertensive response. RESULTS: Cats
      that required a greater dose of amlodipine had significantly higher SBP at
      diagnosis of hypertension (A: (median [25th, 75th percentile]) 182 [175,192]
      mmHg; B: 207 [194,217] mmHg, P < .001), but comparable blood pressure was
      achieved after treatment. Plasma amlodipine concentrations were directly related
      to the dose of amlodipine administered. At diagnosis, cats in group B had
      significantly lower plasma potassium concentration (A: 4.1 [3.8,4.5]; B: 3.8
      [3.6,4.2] mEq/L, P < .01). Weight did not differ between groups. The decrease in
      SBP was directly and independently associated with the SBP at diagnosis and the
      plasma amlodipine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with
      higher blood pressure at diagnosis might require a greater dose of amlodipine to
      control their blood pressure adequately. Differences in amlodipine
      pharmacokinetics between cats do not seem to play a role in the antihypertensive
      response.

PMID- 27717193
TI  - Barriers and facilitators to asthma self-management in adolescents: A systematic
      review of qualitative and quantitative studies.
AB  - BACKGROUND: Many adolescents have poor asthma control and impaired quality of
      life despite the availability of modern pharmacotherapy. Research suggests that
      poor adherence to treatment and limited engagement in self-management could be
      contributing factors. OBJECTIVE: To conduct a systematic review of the barriers
      and facilitators to self-management of asthma reported by adolescents using a
      narrative synthesis approach to integrate the findings. DESIGN: MEDLINE, EMBASE,
      CINAHL, and PsycINFO were searched for all types of study design. Full papers
      were retrieved for study abstracts that included data from participants aged 12
      18 years referring to barriers or facilitators of asthma self-management
      behaviors. RESULTS: Sixteen studies (5 quantitative and 11 qualitative) underwent
      data extraction, quality appraisal, and thematic analysis. Six key themes were
      generated that encompassed barriers and/or facilitators to self-management of
      asthma in adolescents: Knowledge, Lifestyle, Beliefs and Attitudes,
      Relationships, Intrapersonal Characteristics, and Communication. CONCLUSIONS:
      There is a pressing need to prepare adolescents for self-management, using age
      appropriate strategies that draw on the evidence we have synthesized. Current
      clinical practice should focus on ensuring adolescents have the correct
      knowledge, beliefs, and positive attitude to self-manage their illness. This
      needs to be delivered in a supportive environment that facilitates two-way
      communication, fosters adolescents' self-efficacy to manage their disease, and
      considers the wider social influences that impinge on self-management. Pediatr
      Pulmonol. 2017;52:430-442. (c) 2016 Wiley Periodicals, Inc.

PMID- 27717194
TI  - Associations between changes in glucagon-like peptide-1 and bodyweight reduction
      in patients receiving acarbose or metformin treatment.
AB  - BACKGROUND: The present post hoc analysis investigated whether changes in
      endogenous glucagon-like peptide-1 (?GLP-1) levels are associated with weight
      loss in newly diagnosed diabetes patients. METHODS: In all, 784 subjects from the
      Metformin and AcaRbose in Chinese as initial Hypoglycemic treatment (MARCH) study
      were stratified according to ?GLP-1. Changes in clinical and physiological
      parameters were evaluated across ?GLP-1 subgroups (low, medium, and high) to
      assess correlations between ?GLP-1 and weight loss in acarbose- versus metformin
      treated groups. RESULTS: After 24 weeks treatment, greater ?GLP-1 was associated
      with significantly greater weight loss (-2 vs -1 kg in the medium/high vs low
      ?GLP-1 groups, respectively) and reduction in body mass index (BMI; -0.88, -0.83,
      and -0.69 kg/m2 in the high, medium, and low ?GLP-1 groups, respectively). In the
      acarbose-treated group, there was a significant association between ?GLP-1 and
      BMI reductions, and greater ?GLP-1 across the high, medium, and low ?GLP-1 groups
      was correlated with greater weight loss (-2.8, -2.1, and -1.9 kg, respectively)
      and reductions in fasting plasma glucose (-1.57, -1.28, and -1.02 mmol/L,
      respectively) at Week 24. No significant differences were found across ?GLP-1
      subgroups in metformin-treated patients (P > 0.05). Multivariate linear
      regression analysis revealed that gender, baseline BMI, and ?GLP-1 at Week 24
      were associated with weight loss. Baseline BMI and ?GLP-1 in the acarbose-treated
      group and baseline BMI in the metformin-treated group predicted weight loss at
      Week 24. CONCLUSION: Changes in GLP-1 levels are associated with weight loss in
      newly diagnosed Chinese diabetes patients receiving acarbose.

PMID- 27717195
TI  - A meta-analysis comparing clinical effects of short- or long-acting GLP-1
      receptor agonists versus insulin treatment from head-to-head studies in type 2
      diabetic patients.
AB  - AIMS: To study differences in clinical outcomes between initiating glucagon-like
      peptide-1 receptor agonist (GLP-1 RAs) vs insulin treatment in patients with type
      2 diabetes treated with oral glucose-lowering medications (OGLM). METHODS:
      Prospective, randomized trials comparing GLP-1 RA and insulin treatment head-to
      head as add-on to OGLM were identified (PubMed). Differences from baseline values
      were compared for HbA1c, fasting plasma glucose, bodyweight, blood pressure,
      heartrate and lipoproteins. Proportions of patients reporting hypoglycaemic
      episodes were compared. RESULTS: Of 712 publications identified, 23 describing 19
      clinical trials were included in the meta-analysis. Compared to insulin, GLP-1
      RAs reduced HbA1c more effectively (Delta -.12%, P < .0001). Basal insulin was
      more effective in reducing fasting plasma glucose (Delta -1.8 mmol/L, P < .0001).
      GLP-1 RAs reduced bodyweight more effectively (Delta -3.71 kg; P < .0001). The
      proportion of patients experiencing hypoglycaemic episodes was 34% lower with GLP
      1 RAs ( P < .0001), with a similar trend for severe hypoglycaemia. Systolic blood
      pressure was lower and heartrate was higher with GLP-1 RAs ( P < .0001).
      Triglycerides and LDL cholesterol were significantly lower with GLP-1 RAs. Long
      acting GLP-1 RAs were better than short-acting GLP-1 RAs in reducing HbA1c and
      fasting glucose, but were similar regarding bodyweight. CONCLUSIONS: Slightly
      better glycaemic control can be achieved by adding GLP-1 RAs to OGLM as compared
      to insulin treatment, with added benefits regarding bodyweight, hypoglycaemia,
      blood pressure and lipoproteins. These differences are in contrast to the fact
      that insulin is prescribed far more often than GLP-1 RAs.

PMID- 27717196
TI  - Changes in cellular glycosylation of leukemia cells upon treatment with acridone
      derivatives yield insight into drug action.
AB  - A new acridone derivative 2-aminoacetamido-10-(3, 5-dimethoxy)-benzyl-9(10H)
      acridone hydrochloride (8a) has been shown to have potent antitumor activity. In
      order to understand the underlying action mechanism of 8a, three compounds of the
      same class with structures optimized step-by-step, 9(10H)-acridone (A), 10-(3,5
      dimethoxy) benzyl-9(10H)-acridone (I) and 8a, were exposed to CCRF-CEM leukemia
      cell to determine the N-glycosylation changes using the microfluidic HPLC-chip
      TOF MS platform. N-Glycans from whole cell lysates (WCL) and cell membranes (CM)
      were analyzed using isomer-sensitive chip-based porous graphitized carbon nano
      LC/MS. A total of 223 N-glycan compositions and 398 N-glycan compounds were
      identified. Comparison of the two analyses showed that more apparent changes were
      observed in the CM compared with WCL, suggesting that CM may be a more sensitive
      indicator of changes in glycosylation. Upon 8a exposure to CCRF-CEM cells, a
      significant decrease in high-mannose-type glycans was observed. Different
      expressions of oligosaccharyltransferase subunits appear to play a key functional
      role in regulating the hypoglycosylation and contribute to the action mechanism
      of 8a. Taken together our findings suggest that glycosylation is strongly
      affected by therapeutic potency and can be used as possible biomarkers for
      monitoring toxicity and antitumor activity of 8a.

PMID- 27717197
TI  - Postoperative value of serum squamous cell carcinoma antigen as a predictor of
      recurrence in sinonasal inverted papilloma.
AB  - OBJECTIVES: Sinonasal inverted papilloma (IP) has several unfavourable
      characteristics and therefore requires careful monitoring. The goal of this study
      was to identify whether serum squamous cell carcinoma antigen (SCCa) could
      predict IP recurrence. DESIGN: A retrospective cohort study. SETTING: Department
      of otolaryngology/head and neck surgery, Erasmus Medical Centre, Rotterdam, the
      Netherlands. PARTICIPANTS: One hundred and thirty patients with IP treated at our
      centre with SCCa measurements available were included. MAIN OUTCOME MEASUREMENTS:
      Follow-up of patients with IP since 2005, recurrence was defined as new disease
      within primary localisation at least 3 months after adequate surgical removal. We
      analysed the association between IP recurrence and serum SCCa values measured
      preoperatively, postoperatively and during follow-up. RESULTS: Preoperative SCCa
      values or values measured during follow-up were not associated with risk of
      recurrence. Postoperative SCCa was positively associated with the risk of
      recurrence (P < 0.001). Postoperative SCCa had a good discriminative ability for
      the identification of recurrence with an area under the curve of 80.9%.
      CONCLUSION: Postoperative SCCa is strongly associated with risk of recurrence.
      This might help the surgeon in the postoperative setting by identifying high-risk
      patients and planning follow-up strategy tailored to the individual patient.

PMID- 27717198
TI  - Young investigator challenge: Can the Ion AmpliSeq Cancer Hotspot Panel v2 be
      used for next-generation sequencing of thyroid FNA samples?
AB  - BACKGROUND: Fine-needle aspiration (FNA) cytology is accurate and cost-effective
      in the evaluation of thyroid nodules. Molecular techniques may contribute to risk
      stratification in indeterminate cases. Although next-generation sequencing (NGS)
      is a promising technique for the molecular testing of thyroid FNA specimens,
      thyroid-specific cancer gene panels are not commercially available. Conversely,
      the Ion AmpliSeq Cancer Hotspot Panel v2 (CHPv2), which includes the genes most
      frequently mutated in thyroid neoplasms, is commercially available and may
      represent an alternative to thyroid-specific panels. To the authors' knowledge to
      date, CHPv2 has performed well only on "ideal" cytological samples featuring
      abundant, high-quality DNA and satisfactory postsequencing metrics. The objective
      of the current study was to extend NGS to less-than-ideal samples, which
      represent a large percentage of routine clinical specimens. METHODS: A total of
      37 thyroid smears were retrospectively analyzed using CHPv2, regardless of any
      preanalytical and postsequencing metric thresholds. Specifically, the authors
      evaluated the performance of CHPv2 on the BRAF, NRAS, HRAS, KRAS, and RET genes.
      Results were verified by pyrosequencing. RESULTS: Of the 37 thyroid FNA
      specimens, 34 (91.8%) were successfully processed. BRAF, NRAS, and RET somatic
      variants were detected in 22 of these 34 specimens (64.7%). NGS was found to have
      a high sensitivity (89.4%), specificity (85.7%), and accuracy (88.4%).
      CONCLUSIONS: CHPv2 is a valid option for the molecular evaluation of thyroid FNA
      specimens by NGS. It is interesting to note that this approach is accurate and
      effective even when applied to routine cytology samples that usually do not have
      optimal preanalytical and postsequencing requirements. Cancer Cytopathol
      2016;124:776-84. (c) 2016 American Cancer Society.

PMID- 27717200
TI  - Spotlights on our sister journals: Chem. Eur. J. 39/2016.

PMID- 27717199
TI  - Corrigendum: Base-Catalyzed Highly Stereoselective Conversion of gamma-Hydroxy
      alpha,beta-acetylenic Esters to gamma-Acetoxy Dienoates.

PMID- 27717201
TI  - Tunable Supramolecular Interactions of Aggregation-Induced Emission Probe and
      Graphene Oxide with Biomolecules: An Approach toward Ultrasensitive Label-Free
      and "Turn-On" DNA Sensing.
AB  - Aggregation-induced emission (AIE) probes have shown great potential applications
      in fluorescent sensing of biomolecules, and the integration of AIE probe and
      graphene oxide (GO) attracts intense interest in developing new tools for label
      free and "turn-on" fluorescent biomolecular analysis. Herein, an ultrasensitive
      label-free and "turn-on" DNA sensing is realized by tuning the supramolecular
      interactions of AIE probe and GO with DNA. The investigation of supramolecular
      interactions of AIE probes and GO with DNA demonstrate that AIE probe with short
      alkyl chains substitute shows highest binding affinity with DNA strand, and GO
      with low oxidation degree possesses strong binding interactions to ssDNA and the
      highest fluorescence quenching efficiency. As a result, the optimized AIE probes
      and GO-based fluorescent sensor can selectively detect the target DNA sequence
      and exhibits the detection limitation as low as 0.17 * 10-9 m. It is believed
      that the research efforts will provide an efficient approach to improve the
      performance of DNA sensing assay and an indepth understanding of the
      supramolecular interactions of AIE probes and GO with DNA, and thus facilitate
      their extended applications in biosensors and biomedicine.

PMID- 27717202
TI  - Induction of multiple ovulation via modulation of angiotensin II receptors in in
      vitro ovarian follicle culture models.
AB  - In vitro culture of ovarian follicles is a promising bioengineering technique for
      retrieving fertilizable oocytes from preserved ovarian tissues of cancer
      survivors. However, current in vitro follicle culture techniques are labour
      intensive and of low efficiency, as only single follicle culture (SFC) has been
      possible to date. The present study investigated the feasibility of
      multifollicular cluster culture (MFCC) system using angiotensin II receptor (ATII
      Rc) analogues. Ovarian pre-antral follicles isolated from 2-week-old C57BL6 mice
      were cultured with ATII-Rc agonist or antagonist and their maturation outcomes
      were compared with control group. When single follicles were cultured, the
      ovulation and maturation rates were similar in all three groups. When three
      follicle clusters were cultured, up to three follicles were ovulated in the ATII
      Rc agonist group while none or one follicle ovulated in control or antagonist
      groups (p < 0.0001). Significantly higher numbers of mature oocytes were obtained
      in the agonist group (three-follicle 28.2 +/- 4.9 vs. SFC 11.0 +/- 1.3, per 25
      cultured droplets) (p < 0.0001), and the development of each fertilized oocytes
      was comparable to those from SFC. It is therefore concluded that this novel MFCC
      system can significantly improve the efficiency of in vitro mature oocyte
      retrieval via ATII-Rc modulation. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27717203
TI  - Anterior regeneration after fission in the holothurian Cladolabes schmeltzii
      (Dendrochirotida: Holothuroidea).
AB  - The regeneration of the anterior portion of the body after fission was studied in
      the holothurian Cladolabes schmeltzii using electron microscopy methods.
      Following fission, the posterior portion of the digestive tube, cloaca, and
      respiratory trees remain in the posterior fragment of the body. The regeneration
      comprises five stages. In the first stage, connective-tissue thickening (an
      anlage of the aquapharyngeal bulb) occurs on the anterior end between the torn
      off ends of the ambulacra. Most of the lost anterior organs developed in the
      second and third stages. The structures of water-vascular system and nerve ring
      form through dedifferentiation, proliferation, and migration of cells of the
      radial water-vascular canals and the radial nerve cords, correspondently. The
      lost digestive system portion is restored through the formation and merging of
      two anlagen. The digestive epithelium of the esophagus and pharynx develops from
      lining cells of microcavities near the central portion of the connective-tissue
      thickening, which probably migrate from the epidermis. The second gut anlage
      develops through transformation of the anterior gut remnant portion. The
      enterocytes partly dedifferentiate, but the epithelium retains integrity. The gut
      anlage grows down the mesentery and joins the regenerating aquapharyngeal bulb.
      In the fourth and fifth stages, all lost organs are formed and have nearly normal
      structure. The regeneration was concluded to occur through morphallactic
      rearrangements of the remaining parts of organs. Epithelial morphogenesis is the
      key development mechanism of the digestive, water-vascular, and nervous systems.

PMID- 27717204
TI  - Treatment modalities in sinonasal undifferentiated carcinoma: an analysis from
      the national cancer database.
AB  - BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive
      malignancy of unknown etiology with a poor overall prognosis. Its relative rarity
      has made it difficult to determine the impact of different treatment modalities
      on survival. METHODS: Retrospective study of cases in the National Cancer Data
      Base (NCDB). NCDB cases that were diagnosed as having SNUC between January 1,
      2004, and December 31, 2013 were included in the analysis. Outcomes of patients
      treated with surgery followed adjuvant chemoradiotherapy were compared with
      definitive chemoradiotherapy. RESULTS: A 5-year survival rate of 42.2% was
      observed in the 460 patients in the analysis. American Joint Committee on Cancer
      (AJCC) clinical staging data were available for 304 patients. Of these patients,
      60.2% had advanced tumors (AJCC stage 3 or 4). Surgery followed by adjuvant
      chemoradiotherapy was associated with better survival than definitive
      chemoradiotherapy (55.8% vs 42.6%, p = 0.007) in the study population. However,
      in late-stage tumors, there was no difference in survival between the 2 treatment
      groups (p = 0.22). For late-stage tumors, the time to initiation of adjuvant
      therapy was 49.2 +/- 5.1 days for the surgery plus adjuvant therapy group as
      compared with 25.9 +/- 2.6 days in the definitive chemoradiotherapy group (p <
      0.0001), yet this did not appear to affect outcomes. No differences in age,
      gender, race, Charlson-Deyo score, facility type (academic vs nonacademic), or
      radiation dose were found between the 2 treatment groups (p > 0.05). Margin
      status played a critical role in the success of surgical resection, as no
      patients with positive margin status receiving adjuvant therapy survived to 5
      years. CONCLUSION: Surgery may play a role in a multimodality approach to
      treatment of late-stage SNUC if the tumor is amenable to surgical resection and
      negative margins can be reliably obtained. However, in cases where there may be
      difficulty obtaining negative margins, or this is considered unlikely
      preoperatively, surgical resection does not appear to provide any additional
      survival benefit.

PMID- 27717205
TI  - Head-to-Head Linkage Containing Bithiophene-Based Polymeric Semiconductors for
      Highly Efficient Polymer Solar Cells.
AB  - Narrow bandgap (1.37-1.46 eV) polymers incorporating a head-to-head linkage
      containing 3-alkoxy-3'-alkyl-2,2'-bithiophene are synthesized. The head-to-head
      linkage enables polymers with sufficient solubility and the noncovalent sulfur
      oxygen interaction affords polymers with high degree of backbone planarity and
      film ordering. When integrated into polymer solar cells, the polymers show a
      promising power conversion efficiency approaching 10%.

PMID- 27717206
TI  - Epigenetic silencing of miR-200c in breast cancer is associated with
      aggressiveness and is modulated by ZEB1.
AB  - Loss of expression of miR-200 family members has been implicated in cellular
      plasticity, a phenomenon that accounts for epithelial-to-mesenchymal transition
      (EMT) and stem-like features of many carcinomas and is considered a major cause
      of tumor aggressiveness and drug resistance. Nevertheless, the mechanisms of miR
      200 downregulation in breast cancer are still largely unknown. Here we show that
      miR-200c expression inversely correlates with miR-200c/miR-141 locus methylation
      in triple-negative breast tumors (TNBC). Importantly, low levels of miR-200c
      expression and high levels of miR-200c/miR-141 locus methylation associated with
      lymph node metastasis. Moreover, miR-200c/miR-141 locus methylation was
      significantly related to high expression of ZEB1 in two independent TNBC series.
      Silencing of ZEB1 in vitro reduced miR-200c/miR-141 DNA methylation and,
      concurrently, decreased histone H3K9 trimethylation. This chromatin modifications
      were paralleled by an increase in the expression of both miR-200c and E-cadherin.
      Similar effects were achieved by treatment with a demethylating agent. Our data
      suggest that gene methylation is an important element in the regulation of the
      miR-200c/ZEB1 axis and that chromatin remodeling of the miR-200c/miR-141 locus is
      affected by ZEB1 and, thus, contributes to ZEB1-induced cellular plasticity. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27717207
TI  - Improved Photocatalytic H2 Evolution over G-Carbon Nitride with Enhanced In-Plane
      Ordering.
AB  - A series of rod-like porous graphitic-carbon nitrides (short as CNs) with
      enhanced in-plane ordering have been fabricated through self-assembled heptazine
      hydrate precursors for the first time. By controlling the calcination of the
      preformed precursors with different temperature-rising rates, the resulted CNs
      (SAHEP-CNs-1) with the most ordered and least stacked graphitic planar are
      showing a tremendously improved hydrogen evolution rate of 420 MUmol h-1 under
      visible light and a remarkable apparent quantum efficiency of 8.9% at 420 nm,
      which is among the highest values for C3 N4 -related photocatalysts in the
      literature. This work discloses that enhancing in-plane ordering is one critical
      factor for improving the photocatalytic H2 evolution of carbon nitride, which is
      an effective solution to prolong the lifetime of charge carriers by accelerating
      the charge transport and separation within the graphitic planar. This finding
      would present a facial strategy for the designing of efficient organic
      semiconductors for photocatalysis.

PMID- 27717208
TI  - Copolymer-Mediated Cell Aggregation Promotes a Proangiogenic Stem Cell Phenotype
      In Vitro and In Vivo.
AB  - Material-induced cell aggregation drives a proangiogenic expression profile.
      Copolymer substrates containing cell-repellent and cell-adhesive domains force
      the aggregation of human mesenchymal stem cells, which results in enhanced
      tubulogenesis in vitro and stabilization of vasculature in vivo. These findings
      can be used to design instructive biomaterial scaffolds for clinical use.

PMID- 27717209
TI  - Is quercetin an alternative natural crosslinking agent to genipin for long-term
      dermal scaffolds implantation?
AB  - As biocompatible matrices, porcine dermal scaffolds have limited application in
      tissue engineering due to rapid degradation following implantation. This study
      compared the physical, chemical and biomechanical changes that occurred when
      genipin and quercetin were used to crosslink dermal scaffolds and to determine
      whether quercetin could be used as an alternative to genipin. Physicochemical
      changes in the collagen were assessed using spectroscopic methods [X-ray
      diffraction analysis (XRD) and nuclear magnetic resonance (NMR) analysis]. The
      crosslinking reaction was evaluated by quantification of amino acids and the
      degree of this reaction by ninhydrin assay. Because the mechanical behaviour of
      the collagen matrices is highly influenced by crosslinking, the tensile strength
      of both sets of scaffolds was evaluated. The highest mechanical strength,
      stiffness, degree of crosslinking and changes in the packing features of collagen
      (measured by XRD) were achieved using genipin. Some of the results found in the
      quercetin-crosslinked scaffolds were possibly due to hydration and dehydration
      effects elicited by the solvents (phosphate-buffered saline or ethanol), as seen
      in the NMR results. In the quercetin-ethanol-crosslinked scaffolds, possible
      reorientation of the amino groups of the collagen molecule may have taken place.
      Therefore, depending on their proximity to the crosslinking reagent, different
      types and numbers of interactions may have occurred, inducing a higher
      crosslinking degree (as evidenced by the ninhydrin assay) and reduction in the
      free amino acids after reaction. Both crosslinking agents and solvents interfere
      in the physicochemical properties of collagen thereby inducing variations in the
      matrix structure. Quercetin-crosslinked scaffolds may have broader clinical
      application where a lower degree of crosslinking and stiffness is required.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27717211
TI  - Offers of appointments with nurse practitioners if a requested physician is
      unavailable.
AB  - BACKGROUND AND PURPOSE: Access to primary care remains a problem for a
      substantial portion of the U.S. population, and is predicted to worsen due to an
      aging population and the increasing burden of chronic diseases. Better
      integration of nurse practitioners (NPs) into the primary care workforce is a
      possible solution. We examine offers of appointments with NPs if a requested
      primary care physician is unavailable. METHODS: Data are from a 2013 audit
      (simulated patient) study requesting appointment information from a national
      random sample of primary care physicians. Outcome variables include appointment
      offers, wait-to-appointment times, and appointment offers with alternate
      providers, including NPs. CONCLUSIONS: Of 922 calls to primary care physicians
      serving the general adult population, 378 (41%) offered appointments with the
      requested physician. Alternate providers were offered by 63 (7%), including nine
      offers with NPs (<1%). Mean wait-to-appointment for NPs (3.6 days) was
      statistically significantly shorter (p-values < .01) than for requested
      physicians (22.5 days) or non-NP alternate providers (23.9 days). IMPLICATIONS
      FOR PRACTICE: NPs are an important part of the primary care workforce, and new
      patients seeking primary care physicians may substantially reduce their wait
      times if an NP is offered.

PMID- 27717210
TI  - Patient-reported outcomes and aesthetic evaluation of root coverage procedures: a
      12-month follow-up of a randomized controlled clinical trial.
AB  - AIM: To assess patient-reported outcome measures (PROMs), aesthetics and
      stability of root coverage procedures from a previous 6-month RCT after 1 year.
      MATERIAL & METHODS: Forty-five patients (90 recessions) had received a coronally
      advanced flap (CAF = control) only or a xenogeneic collagen matrix in addition
      (CAF + CMX = test). Visual analogue scales (VAS) and questionnaires were used for
      PROMs and the root coverage aesthetic score (RES) for professional aesthetic
      evaluations. RESULTS: VAS scores (patient satisfaction) amounted to 8.58 +/- 1.86
      (test) versus 8.38 +/- 2.46 (control). Six patients preferred CAF + CMX
      concerning surgical procedure and aesthetics, six preferred CAF and 29 were
      equally satisfied. RES was 7.85 +/- 2.42 for the test group versus 7.34 +/- 2.90
      for the controls. Root coverage (RC) was 76.28% for test and 75.05% for control
      defects. The mean increase in keratinized tissue width was higher in test (from
      1.97 to 3.02 mm) than in controls (from 2.00 to 2.64 mm) (p = 0.0413). Likewise,
      test sites showed more gain in gingival thickness (0.52 mm) than control sites
      (0.27 mm) (p = 0.0023). Compared to 6 months, clinical outcomes were stable.
      CONCLUSIONS: Results for PROMs, RES and RC did not significantly differ between
      treatment groups. Thickness and width of keratinized tissue were enhanced
      following CAF + CMX compared to CAF alone.

PMID- 27717212
TI  - Side-Chain Fluorination: An Effective Approach to Achieving High-Performance All
      Polymer Solar Cells with Efficiency Exceeding 7.
AB  - Side-chain fluorination of polymers is demonstrated as a highly effective
      strategy to improve the efficiency of all-polymer solar cells from 2.93%
      (nonfluorinated P1) to 7.13% (fluorinated P2). This significant enhancement is
      achieved by synergistic improvements in open-circuit voltage, charge generation,
      and charge transport, as fluorination of the donor polymer optimizes the band
      alignment and the film morphology.

PMID- 27717214
TI  - Electron Delocalization in Perylene Diimide Helicenes.
AB  - We report two new helicenes derived from the double fusion of an acene with two
      perylene diimide (PDI) subunits. These PDI-helicene homologs exhibit very
      different structural and electronic properties, despite differing by only a
      single ring in the link between the PDI units. The shorter inter-PDI link brings
      the two PDI subunits closer together, and this results in the collision of their
      respective pi-electron clouds. This collision facilitates intramolecular through
      space electronic delocalization when the PDI-helicene is reduced.

PMID- 27717215
TI  - DNA barcodes of the native ray-finned fishes in Taiwan.
AB  - Species identification based on the DNA sequence of a fragment of the cytochrome
      c oxidase subunit I gene in the mitochondrial genome, DNA barcoding, is widely
      applied to assist in sustainable exploitation of fish resources and the
      protection of fish biodiversity. The aim of this study was to establish a
      reliable barcoding reference database of the native ray-finned fishes in Taiwan.
      A total of 2993 individuals, belonging to 1245 species within 637 genera, 184
      families and 29 orders of ray-finned fishes and representing approximately 40% of
      the recorded ray-finned fishes in Taiwan, were PCR amplified at the barcode
      region and bidirectionally sequenced. The mean length of the 2993 barcodes is 549
      bp. Mean congeneric K2P distance (15.24%) is approximately 10-fold higher than
      the mean conspecific one (1.51%), but approximately 1.4-fold less than the mean
      genetic distance between families (20.80%). The Barcode Index Number (BIN)
      discordance report shows that 2993 specimens represent 1275 BINs and, among them,
      86 BINs are singletons, 570 BINs are taxonomically concordant, and the other 619
      BINs are taxonomically discordant. Barcode gap analysis also revealed that more
      than 90% of the collected fishes in this study can be discriminated by DNA
      barcoding. Overall, the barcoding reference database established by this study
      reveals the need for taxonomic revisions and voucher specimen rechecks, in
      addition to assisting in the management of Taiwan's fish resources and diversity.

PMID- 27717213
TI  - The brain-derived neurotrophic factor Val66Met polymorphism affects encoding of
      object locations during active navigation.
AB  - The brain-derived neurotrophic factor (BDNF) was shown to be involved in spatial
      memory and spatial strategy preference. A naturally occurring single nucleotide
      polymorphism of the BDNF gene (Val66Met) affects activity-dependent secretion of
      BDNF. The current event-related fMRI study on preselected groups of 'Met'
      carriers and homozygotes of the 'Val' allele investigated the role of this
      polymorphism on encoding and retrieval in a virtual navigation task in 37 healthy
      volunteers. In each trial, participants navigated toward a target object. During
      encoding, three positional cues (columns) with directional cues (shadows) were
      available. During retrieval, the invisible target had to be replaced while either
      two objects without shadows (objects trial) or one object with a shadow (shadow
      trial) were available. The experiment consisted of blocks, informing participants
      of which trial type would be most likely to occur during retrieval. We observed
      no differences between genetic groups in task performance or time to complete the
      navigation tasks. The imaging results show that Met carriers compared to Val
      homozygotes activate the left hippocampus more during successful object location
      memory encoding. The observed effects were independent of non-significant
      performance differences or volumetric differences in the hippocampus. These
      results indicate that variations of the BDNF gene affect memory encoding during
      spatial navigation, suggesting that lower levels of BDNF in the hippocampus
      results in less efficient spatial memory processing.

PMID- 27717217
TI  - Histopathological features of a patient with Charcot-Marie-Tooth disease type
      2U/AD-CMTax-MARS.
AB  - Charcot-Marie-Tooth (CMT) disease is a complex of peripheral nervous system
      disorders. CMT type 2U (CMT2U) is an autosomal dominant (AD) disease caused by
      mutations in the MARS gene encoding methionyl-tRNA synthetase; this disease has
      thus been newly called AD-CMTax-MARS. A few families with mutations in the MARS
      gene have been reported, without detailed histopathological findings. We describe
      a 70-year-old woman who had bilateral dysesthesia of the soles since the age of
      66 years. Sural nerve biopsy showed a decrease in the density of large myelinated
      nerve fibers. Increased clusters of regenerating myelinated nerve fibers were
      noted. Electron microscopic analyses revealed degeneration of unmyelinated
      nerves. There was no vasculitis or inflammatory cell infiltration. Genetic
      analysis identified a heterozygous p.P800T mutation, a reported mutation in the
      MARS gene. We report the detailed histopathological findings in a patient with
      CMT2U/AD-CMTax-MARS. The findings are similar to those found in CMT2D caused by
      mutations in the GARS gene, encoding glycyl-tRNA synthetase.

PMID- 27717216
TI  - Simulation, phantom validation, and clinical evaluation of fast pH-weighted
      molecular imaging using amine chemical exchange saturation transfer echo planar
      imaging (CEST-EPI) in glioma at 3 T.
AB  - Acidity within the extracellular milieu is a hallmark of cancer. There is a
      current need for fast, high spatial resolution pH imaging techniques for clinical
      evaluation of cancers, including gliomas. Chemical exchange saturation transfer
      (CEST) MRI targeting fast-exchanging amine protons can be used to obtain high
      resolution pH-weighted images, but conventional CEST acquisition strategies are
      slow. There is also a need for more accurate MR simulations to better understand
      the effects of amine CEST pulse sequence parameters on pH-weighted image
      contrast. In the current study we present a simulation of amine CEST contrast
      specific for a newly developed CEST echoplanar imaging (EPI) pulse sequence. The
      accuracy of the simulations was validated by comparing the exchange rates and Z
      spectrum under a variety of conditions using physical phantoms of glutamine with
      different pH values. The effects of saturation pulse shapes, pulse durations,
      pulse train lengths, repetition times, and relaxation rates of bulk water and
      exchangeable amine protons on the CEST signal were explored for normal-appearing
      white matter (NAWM), glioma, and cerebrospinal fluid. Last, 18 patients with WHO
      II-IV gliomas were evaluated. Results showed that the Z-spectrum was highly
      dependent on saturation pulse shape, repetition time, saturation amplitude,
      magnetic field strength, and T2 within bulk water; however, the Z-spectrum was
      only minimally influenced by saturation pulse duration and the specific
      relaxation rates of amine protons. Results suggest that a Gaussian saturation
      pulse train consisting of 3 * 100 ms pulses using the minimum allowable
      repetition time is optimal for achieving over 90% available contrast across all
      tissues. Results also demonstrate that high saturation pulse amplitude and
      scanner field strength (>3 T) are necessary for adequate endogenous pH-weighted
      amine CEST contrast. pH-weighted amine CEST contrast increased with increasing
      tumor grade, with glioblastoma showing significantly higher contrast compared
      with WHO II or III gliomas.

PMID- 27717220
TI  - Nurse practitioners and intent to retire.
AB  - BACKGROUND AND PURPOSE: Demand for primary care services is rising. Nurse
      practitioners (NPs) serve vital roles in meeting primary care demands. Workforce
      planning requires understanding NP retirement intentions. This study examines
      factors that relate to NPs, aged 55 years and older, and their intent to retire
      within 5 years. METHODS: We used the 2012 National Sample Survey of Nurse
      Practitioners to examine the relationship between NP demographic characteristics
      (gender, race/ethnicity, marital status, nursing degree), work environment
      characteristics (part-time vs. full-time status, primary or specialty care,
      earnings, job satisfaction), and intent to retire. Descriptive, bivariate, and
      multivariate analyses were conducted. A total of 3171 working NPs, 55 years of
      age and older, were included. CONCLUSIONS: Fifty-nine percent of NPs 60 years and
      older and 15% of NPs 55-59 intend to retire in the next 5 years. Working part
      time and having less than a master's degree were associated with intent to
      retire. Being "very satisfied" with one's job was related to lower odds of intent
      to retire versus being "satisfied." Being "dissatisfied" with one's job and
      working in primary care were related to intending to retire for the NPs 55-59.
      IMPLICATIONS FOR PRACTICE: Given the relationship between higher job satisfaction
      and lower intent to retire, efforts to increase NPs' job satisfaction may result
      in less early retirement.

PMID- 27717219
TI  - Comprehensive management of recurrent thyroid cancer: An American Head and Neck
      Society consensus statement: AHNS consensus statement.
AB  - This American Head and Neck Society (AHNS) consensus statement focuses on the
      detection and management of recurrent thyroid cancer. This document describes the
      radiologic approach to defining structural recurrent disease and the operative
      and nonoperative rationale in addressing identified structural disease to create
      equipoise in the personalized treatment strategy for the patient. The
      recommendations of this AHNS multidisciplinary consensus panel of the American
      Head and Neck Society are intended to help guide all multidisciplinary clinicians
      who diagnose or manage adult patients with thyroid cancer. The consensus panel is
      comprised of members of the American Head and Neck Society and its Endocrine
      Surgical Committee, and there is representation from medical endocrinology and
      both national and international surgical representation drawn from
      general/endocrine surgery and otolaryngology/head and neck surgery. Authors
      provided expertise for their respective sections, and consensus recommendations
      were made regarding the evaluation and treatment of recurrent thyroid cancer.
      Evidence-based literature support is drawn from thyroid cancer studies, recurrent
      thyroid cancer studies, and American Thyroid Association (ATA) guidelines. The
      manuscript was then distributed to members of the American Head and Neck Society
      Endocrine Committee and governing counsel for further feedback. (c) 2016 Wiley
      Periodicals, Inc. Head Neck 38: 1862-1869, 2016.

PMID- 27717221
TI  - Very High Solid State Photoluminescence Quantum Yields of
      Poly(tetraphenylethylene) Derivatives.
AB  - Five different poly(arylene-diarylvinylene)s have been synthesized by reductive
      polyolefination starting from the corresponding bis(alpha,alpha-dichlorobenzyl)
      substituted monomers and dicobaltoctacarbonyl as reducing agent. The resulting
      polymers all contain main chain tetraphenylethylene units. Thanks to the
      aggregation-induced emission effect, the corresponding polymer films show
      remarkably high photoluminescence quantum yields (PLQYs) of 32%-73%. The polymer
      with the highest PLQY is tested as solid state sensing material for the PL
      quenching-based detection of nitroaromatic analytes (1,3,5-trinitrobenzene as
      prototypical analyte).

PMID- 27717225
TI  - SINANO 10th Anniversary Special Issue.

PMID- 27717223
TI  - Case series of omalizumab for allergic bronchopulmonary aspergillosis in cystic
      fibrosis patients.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) affects up to 15% of patients with
      cystic fibrosis (CF). Corticosteroids are used as first-line therapy, but relapse
      and adverse effects commonly occur. Case reports have suggested the efficacy of
      the anti-IgE recombinant humanized monoclonal antibody omalizumab. A
      retrospective multicenter observational French study retrieved 32 CF patients (11
      children and 21 adults) who have received omalizumab for more than 3 months in
      the context of ABPA. Clinical characteristics, concomitant medications (inhaled
      and oral corticosteroids, antifungal drugs), lung function, body mass index
      (BMI), and serum IgE were compared at the start and during the first year of
      omalizumab therapy. Omalizumab-related adverse effects and costs were also
      evaluated. No significant difference with omalizumab could be demonstrated with
      regard to lung function, BMI, or the number of patients receiving oral
      corticosteroids. At the time of initiation of omalizumab, 56% of patients were
      receiving oral corticosteroids. Five patients were able to discontinue
      corticosteroids during follow-up and nine patients were able to reduce their
      daily dose. A total of 78% of the patients had received antifungal therapy at the
      time of the initiation of omalizumab. Treatment tolerance was good (12.5% of
      patients experienced side effects). The median cost of omalizumab treatment was
      ?3,620 per patient per month. Omalizumab may represent a steroid-sparing therapy
      in CF patients with ABPA. A randomized-controlled trial is urgently required to
      provide higher level of evidence regarding the efficacy and cost-effectiveness of
      omalizumab in CF patients with ABPA. Pediatr Pulmonol. 2017;52:190-197. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27717222
TI  - Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic
      treated patients with schizophrenia: a randomized, placebo-controlled trial.
AB  - AIMS: Schizophrenia is associated with cardiovascular co-morbidity and a reduced
      life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor
      antagonists and are the standard of medical care in schizophrenia, but the drugs
      are associated with severe metabolic side effects such as obesity and diabetes.
      Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment
      of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP
      1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese
      patients with schizophrenia. MATERIAL AND METHODS: Antipsychotic-treated, obese,
      non-diabetic, schizophrenia spectrum patients were randomized to double-blinded
      adjunctive treatment with once-weekly subcutaneous exenatide (n = 23) or placebo
      (n = 22) injections for 3 months. The primary outcome was loss of body weight
      after treatment and repeated measures analysis of variance was used as
      statistical analysis. RESULTS: Between March 2013 and June 2015, 40 patients
      completed the trial. At baseline, mean body weight was 118.3 +/- 16.0 kg in the
      exenatide group and 111.7 +/- 18.0 kg in the placebo group, with no group
      differences ( P = .23). The exenatide and placebo groups experienced significant
      ( P = .004), however similar ( P = .98), weight losses of 2.24 +/- 3.3 and 2.23
      +/- 4.4 kg, respectively, after 3 months of treatment. CONCLUSIONS: Treatment
      with exenatide once-weekly did not promote weight loss in obese, antipsychotic
      treated patients with schizophrenia compared to placebo. Our results could
      suggest that the body weight-lowering effect of GLP-1RAs involves dopaminergic
      signaling, but blockade of other receptor systems may also play a role.
      Nevertheless, anti-obesity regimens effective in the general population may not
      be readily implemented in antipsychotic-treated patients with schizophrenia.

PMID- 27717226
TI  - Atomic-Scale Preparation of Octopod Nanoframes with High-Index Facets as Highly
      Active and Stable Catalysts.
AB  - An atomic-scale engineered octopod nanoframe architecture (OFA) consisting of 3D
      catalytic surfaces and beneficial high-index facets is developed via a facile one
      pot synthesis method. Based on the reliable recipe and general method, various
      complex nanoframe architectures are developed. Specially, the PtCu OFAs exhibit
      exceptional activity and stability for the oxygen reduction reaction and can be
      easily scaled up to high-quality.

PMID- 27717228
TI  - The consequences of facultative sex in a prey adapting to predation.
AB  - A species reproductive mode, along with its associated costs and benefits, can
      play a significant role in its evolution and survival. Facultative sexuality,
      being able to reproduce both sexually and asexually, has been deemed evolutionary
      favourable as the benefits of either mode may be fully realized. In fact, many
      studies have focused on identifying the benefits of sex and/or the forces
      selecting for increased rates of sex using facultative sexual species. The costs
      of either mode, however, can also have a profound impact on a population's
      evolutionary trajectory. Here, we used experimental evolution and fitness assays
      to investigate the consequences of facultative sexuality in prey adapting to
      predation. Specifically, we compared the adaptive response of algal prey
      populations exposed to constant rotifer predation and which had alternating
      cycles of asexual and sexual reproduction where sexual episodes were either
      facultative (sexual and asexual progeny simultaneously propagated) or obligate
      (only sexual progeny propagated). We found that prey populations with facultative
      sexual episodes reached a lower final relative fitness and suffered a greater
      trade-off in traits under selection, that is defence and competitive ability, as
      compared to prey populations with obligate sexual episodes. Our results suggest
      that costs associated with sexual reproduction (germination time) and asexual
      reproduction (selection interference) were amplified in the facultative sexual
      prey populations, leading to a reduction in the net advantage of sexuality.
      Additionally, we found evidence that the cost of sex was reduced in the obligate
      sexual prey populations because increased selection for sex was observed via the
      spontaneous production of sexual cells. These results show that certain costs
      associated with facultative sexuality can affect an organism's evolutionary
      trajectory.

PMID- 27717227
TI  - Continuous Production of Discrete Plasmid DNA-Polycation Nanoparticles Using
      Flash Nanocomplexation.
AB  - Despite successful demonstration of linear polyethyleneimine (lPEI) as an
      effective carrier for a wide range of gene medicine, including DNA plasmids,
      small interfering RNAs, mRNAs, etc., and continuous improvement of the physical
      properties and biological performance of the polyelectrolyte complex
      nanoparticles prepared from lPEI and nucleic acids, there still exist major
      challenges to produce these nanocomplexes in a scalable manner, particularly for
      lPEI/DNA nanoparticles. This has significantly hindered the progress toward
      clinical translation of these nanoparticle-based gene medicine. Here the authors
      report a flash nanocomplexation (FNC) method that achieves continuous production
      of lPEI/plasmid DNA nanoparticles with narrow size distribution using a confined
      impinging jet device. The method involves the complex coacervation of negatively
      charged DNA plasmid and positive charged lPEI under rapid, highly dynamic, and
      homogeneous mixing conditions, producing polyelectrolyte complex nanoparticles
      with narrow distribution of particle size and shape. The average number of
      plasmid DNA packaged per nanoparticles and its distribution are similar between
      the FNC method and the small-scale batch mixing method. In addition, the
      nanoparticles prepared by these two methods exhibit similar cell transfection
      efficiency. These results confirm that FNC is an effective and scalable method
      that can produce well-controlled lPEI/plasmid DNA nanoparticles.

PMID- 27717230
TI  - Asymptomatic dengue infection may trigger Guillain-Barre syndrome.

PMID- 27717231
TI  - Heterozygous familial hypercholesterolemia: We must develop a new clinical
      paradigm.

PMID- 27717229
TI  - Long-term Use of Z-Hypnotics and Co-medication with Benzodiazepines and Opioids.
AB  - Benzodiazepine-like drugs (z-hypnotics) are the most commonly used drugs for
      treatment of insomnia in Norway. Z-hypnotics are recommended for short-term
      treatment not exceeding 4 weeks. We aimed to study the use of z-hypnotics in the
      adult population in Norway with focus on recurrent use in new users, treatment
      intensity and co-medication with benzodiazepines and opioids in long-term users.
      Data were obtained from the Norwegian Prescription Database. New users in 2009
      were followed through 2013. Recurrent z-hypnotic use was defined as new fillings
      at least once in each of the four 365-day follow-up periods. Age groups of 18-39,
      40-64 and 65+ years were analysed separately for men and women. In 2013, 354,571
      (8.9%) of the population filled at least one prescription of z-hypnotics and the
      prevalence was relatively stable over time. Among the 92,911 new users of z
      hypnotics in 2009, 13,996 (16.8%) received z-hypnotics all four 365-day periods
      of follow-up. In these long-term recurrent users, the treatment intensity was
      high already the second year, with mean annual amounts of 199 and 169 DDDs per
      patient in men and women, respectively. The interquartile differences were
      greatest in the youngest age group. 27.9% of the long-term recurrent users of z
      hypnotics used benzodiazepines the fourth year and 33.9% used opioids. The
      proportions with co-medication increased with level of z-hypnotic treatment
      intensity. Overall, many z-hypnotic users had medicines dispensed for longer
      periods than recommended, and co-medications with drugs that may reinforce the
      central depressing and intoxicating effects were common.

PMID- 27717233
TI  - Mussel Adhesion-Inspired Reverse Transfection Platform Enhances Osteogenic
      Differentiation and Bone Formation of Human Adipose-Derived Stem Cells.
AB  - Using small interfering RNA (siRNA) to regulate gene expression is an emerging
      strategy for stem cell manipulation to improve stem cell therapy. However,
      conventional methods of siRNA delivery into stem cells based on solution-mediated
      transfection are limited due to low transfection efficiency and insufficient
      duration of cell-siRNA contact during lengthy culturing protocols. To overcome
      these limitations, a bio-inspired polymer-mediated reverse transfection system is
      developed consisting of implantable poly(lactic-co-glycolic acid) (PLGA)
      scaffolds functionalized with siRNA-lipidoid nanoparticle (sLNP) complexes via
      polydopamine (pDA) coating. Immobilized sLNP complexes are stably maintained
      without any loss of siRNA on the pDA-coated scaffolds for 2 weeks, likely due to
      the formation of strong covalent bonds between amine groups of sLNP and catechol
      group of pDA. siRNA reverse transfection with the pDA-sLNP-PLGA system does not
      exhibit cytotoxicity and induces efficient silencing of an osteogenesis inhibitor
      gene in human adipose-derived stem cells (hADSCs), resulting in enhanced
      osteogenic differentiation of hADSCs. Finally, hADSCs osteogenically committed on
      the pDA-sLNP-PLGA scaffolds enhanced bone formation in a mouse model of critical
      sized bone defect. Therefore, the bio-inspired reverse transfection system can
      provide an all-in-one platform for genetic modification, differentiation, and
      transplantation of stem cells, simultaneously enabling both stem cell
      manipulation and tissue engineering.

PMID- 27717234
TI  - Can temperament and character features of patients predict alcohol use after
      laryngectomy?
AB  - AIM: Patients with larynx cancer usually use alcohol besides tobacco. It has been
      reported earlier that nearly half of the patients who have undergone laryngectomy
      after larynx cancer diagnosis still continue to consume alcohol after the
      operation. The aim of this study was to compare the mood and character features
      of patients who do or do not consume alcohol during the postoperative period and
      thus to be able to predict the patients who will continue their alcohol use at
      the postoperative period. MATERIALS AND METHODS: The patients who have undergone
      partial or total laryngectomy operation were included in this study. To avoid
      early period treatment stress, it was required that the patients have completed
      their 6 months of postoperative period. The interviews made with the patients
      included filling out of the sociodemographic data form, TCI (temperament and
      character inventory), BDI (Beck depression inventory), BAI (Beck anxiety
      inventory), AUDIT (alcohol use disorders identification test) and CAGE (cut-down,
      annoyed, guilty, eye-opener) inquiry forms. RESULTS: 80 patients who admitted
      alcohol consumption at the time of larynx cancer diagnosis were divided in to two
      groups and, 40% (n = 32) of this patients continued alcohol consumption after
      laryngectomy (Group 1) and 60% (n = 48) cut down on their alcohol use (Group 2).
      A statistically significant difference was observed between Group 1 and Group 2
      at AUDIT and CAGE score averages (P < 0.001, P < 0.001, respectively). When TCI
      data were compared between Group 1 and Group 2, patients who continued their
      alcohol use at the postoperative period had significantly higher novelty seeking
      scores compared to others (P = 0.03). CONCLUSION: Our data suggest that it may be
      possible in the preoperative period to predict the patients who will continue
      their alcohol use in the postoperative period and take precautions.

PMID- 27717235
TI  - Exogenous lipoid pneumonia induced by nasal decongestant.
AB  - INTRODUCTION: Lipoid pneumonia is a clinical condition that may be initially
      asymptomatic or confused with an infectious or malignant lung disease.
      OBJECTIVES: We report four cases of this pathological condition. METHODS: The
      first case concerned an 85-year old woman with bilateral confluent pulmonary
      opacities, ground-glass type. Diagnosis was based on the cytology of the
      bronchoalveolar lavage (BAL) fluid followed by its ultrastructural examination.
      The second case was a 47-year-old man with an isolated pulmonary nodule, which
      was surgically removed; the diagnosis of lipoid pneumonia was formulated on the
      basis of the histological and electron microscopy examination. The third case
      concerned a 73-year-old woman, with bilateral hypodense areas at the bases of the
      lungs where FDG PET/CT scan showed an increased uptake. Diagnosis was formulated
      by BAL cytology and electron microscopy examination. The fourth case was a 69
      year-old man, who performed a virtual colonoscopy for diverticulosis putting in
      evidence a round mass (3 cm in diameter) with two small peripheral nodules,
      located in the pulmonary left lower lobe. The histopathological examination of
      transthoracic biopsy confirmed a lipoid pneumonia. RESULTS AND CONCLUSION: In all
      four cases, it was put in evidence a prolonged use of a nasal decongestant
      containing mineral oils. In literature, the most cases described are
      characterized by a subclinical evolution and were presented as ground glass
      opacities which evolve, in the later phases, in an interstitial involvement or in
      a peripheral mass, simulating a lung tumour.

PMID- 27717237
TI  - Identification and validation of novel small proteins in Pseudomonas putida.
AB  - Small proteins of 50 amino acids or less have been understudied due to
      difficulties that impede their annotation and detection. In order to obtain
      information on small open reading frames (sORFs) in Pseudomonas putida,
      bioinformatic and proteomic approaches were used to identify putative sORFs in
      the well-characterized strain KT2440. A plasmid-based system was established for
      sORF validation, enabling expression of C-terminal sequential peptide affinity
      tagged variants and their detection via protein immunoblotting. Out of 22 tested
      putative sORFs, the expression of 14 sORFs was confirmed, where all except one
      are novel. All of the validated sORFs except one are located adjacent to
      annotated genes on the same strand and three are in close proximity to genes with
      known functions. These include an ABC transporter operon and the two
      transcriptional regulators Fis and CysB involved in biofilm formation and
      cysteine biosynthesis respectively. The work sheds light on the P. putida small
      proteome and small protein identification, a necessary first step towards gaining
      insights into their functions and possible evolutionary implications.

PMID- 27717236
TI  - Effect of vitamin D supplementation on oral glucose tolerance in individuals with
      low vitamin D status and increased risk for developing type 2 diabetes
      (EVIDENCE): A double-blind, randomized, placebo-controlled clinical trial.
AB  - AIMS: Low serum 25-hydroxyvitamin-D (25(OH)D) concentrations are associated with
      insulin resistance, beta-cell dysfunction and type 2 diabetes. We conducted a 24
      week double-blind, randomized, placebo-controlled trial to examine the effect of
      28 000 IU of vitamin D3 once weekly on plasma glucose after a 2 hour-75 g oral
      glucose tolerance test (2hrPC glucose), insulin sensitivity and beta-cell
      function. STUDY DESIGN AND METHODS: A total of 71 participants with serum 25(OH)D
      <=65 nmol/L, impaired fasting glucose and elevated glycated hemoglobin were
      randomly assigned to receive 28 000 IU of vitamin D3 (VitD; n = 35) or placebo (n
      = 36) in cheese once weekly for 24 weeks. The primary outcome was the change in
      2hPC glucose. Secondary outcomes were fasting glucose, fasting and postprandial
      insulin, indices of insulin sensitivity and beta-cell function, glycated
      hemoglobin and lipid profile. Participants underwent an oral glucose tolerance
      test to determine 2hPC glucose. RESULTS: Mean baseline serum 25(OH)D was 48.1 and
      47.6 nmol/L in the VitD and placebo groups, respectively. Serum 25(OH)D
      significantly increased to 98.7 nmol/L (51 nmol/L increase; P < .0001) in the
      VitD group. No significant differences in fasting ( P = .42) or 2hPC glucose ( P
      = .55) or other indices of glucose metabolism, including beta-cell function and
      insulin sensitivity, were observed between groups. A subgroup analysis of
      individuals with 25(OH)D < 50 nmol/L and prediabetes did not change these
      results. The VitD group exhibited a significant reduction in LDL cholesterol (
      0.27 vs 0.01 mmol/L, P = .03). CONCLUSION: Weekly doses of vitamin D3 in
      individuals with suboptimal vitamin D levels who were at risk for type 2 diabetes
      did not improve oral glucose tolerance or markers of glycaemic status.

PMID- 27717238
TI  - Multifunctional WS2 @Poly(ethylene imine) Nanoplatforms for Imaging Guided Gene
      Photothermal Synergistic Therapy of Cancer.
AB  - The combination of photothermal therapy (PTT) with gene therapy (GT) to improve
      PTT efficiency and thus eliminate cancer cells under mild hyperthermia is highly
      needed. Herein, multifunctional WS2 @poly(ethylene imine) (WS2 @PEI) nanoplatform
      has been designed and constructed for gene-photothermal synergistic therapy of
      tumors at mild condition. After a surface modification of WS2 with a positively
      charged PEI, the as-prepared WS2 @PEI nanoplatform can not only act as an
      efficient survivin-siRNA carrier for GT but also exhibit remarkable near-infrared
      (NIR) photothermal effects for PTT. On the one hand, the photothermal effects
      induced by WS2 @PEI upon NIR irradiation can enhance the cellular uptake owing to
      the increase of the cell membrane permeability, which leads to the remarkable
      enhancement of silencing efficiency of survivin. On the other hand, the silencing
      of survivin can increase the apoptosis as well as reduce the heat resistance of
      cancer cells by downregulating the heat shock protein 70 expressions, which
      greatly enhance the sensitivity of cancer cells to PTT. As a result, compared to
      PTT or GT treatment alone, WS2 @PEI mediated synergistic GT/PTT therapy
      remarkably enhances in vitro cancer cell damage and in vivo tumor elimination.

PMID- 27717239
TI  - Strong and Rapidly Self-Healing Hydrogels: Potential Hemostatic Materials.
AB  - Benzaldehyde-terminated telechelic four-armed polyethylene glycol (PEG-BA) is
      synthesized and cross-linked with carboxymethyl chitosan (CMC) to form dynamic
      hydrogels with strong mechanical performance. The gelation temperature and time,
      mechanical performance, and self-healing behaviors are systematically
      investigated. The hydrogels have good storage modulus up to 3162.06 +/- 21.06 Pa,
      comparable to conventional bulk hydrogels. The separated alternate hydrogel lines
      connect together to become an integrated hydrogel film after 5 min at room
      temperature without any external intervention. This is due to the dynamic
      equilibrium between the Schiff base linkages and the aldehyde groups of PEG-BA
      and amine groups on CMC backbone. The hydrogel shows excellent cytocompatibility
      and the cell viability is as high as 90.7 +/- 6.8% after 2 d 3D encapsulation in
      the hydrogel. In vivo tests indicate that the hydrogels can effectively stop
      bleeding when the hydrogel is directly injected into a rabbit liver incision. The
      total blood loss is reduced from 0.65 +/- 0.10 g to 0.29 +/- 0.11 g, and the
      hemostasis time is decreased from 167 +/- 21 s to 120 +/- 10 s, when compared to
      a gauze treatment with physical compression. These self-healing hydrogels have
      potential to be used as a novel hemostatic material.

PMID- 27717240
TI  - Attitudes toward evidence-based clinical decision support tools to reduce
      exposure to ionizing radiation: The Canadian CT Head Rule.
AB  - BACKGROUND AND PURPOSE: A large degree of variation in clinical practice exists
      among clinicians evaluating and treating individuals with minor head injuries.
      Noncontrast head computerized tomography (CT) scans are commonly used to assess
      for intracranial damage in patients presenting with head injury. This practice is
      not supported by the evidence and poses harm to patients by increasing exposure
      to ionizing radiation. This form of radiation exposure increases the risk of
      developing cancers over the course of the individual's life, and further strains
      the limited resources of the healthcare system. PROJECT SUMMARY: This article
      describes the findings of an evidence-based practice project assessing the
      attitudes of clinicians toward an evidence-based clinical decision support tool
      (Canadian CT Head Rule [CCHR]). The CCHR has 100% sensitivity in detecting all
      clinically important brain injuries and any injury requiring neurosurgical
      intervention. This clinical decision support (CDS) tool is designed to help guide
      clinicians in the prudent use of head CT scans in people ages 16-64 that have
      sustained minor head injuries. The Evidence-Based Attitude Scale was also used to
      identify which domains were most influential on willingness to adopt into
      clinical practice. CONCLUSIONS: The results revealed an 84% increase in clinician
      knowledge of the use of the CCHR. A majority (83%) of participants reported
      moderate likelihood of adoption of the CDS tool into clinical practice if they
      found the tool appealing, and it was required by a governing authority. The use
      of CDS tools can help healthcare providers mitigate the risk associated with
      caring for complex patients. CDS tools provide a systematic method to evaluate
      patients with minor head injuries while assuring consistency of care and quality
      outcomes. This practice of assuring consistency and good patient outcomes is
      foundational to the concept of standard of care, which serves to improve clinical
      practice.

PMID- 27717242
TI  - Templated Solid-State Dewetting of Thin Silicon Films.
AB  - Thin film dewetting can be efficiently exploited for the implementation of
      functionalized surfaces over very large scales. Although the formation of sub
      micrometer sized crystals via solid-state dewetting represents a viable method
      for the fabrication of quantum dots and optical meta-surfaces, there are several
      limitations related to the intrinsic features of dewetting in a crystalline
      medium. Disordered spatial organization, size, and shape fluctuations are
      relevant issues not properly addressed so far. This study reports on the
      deterministic nucleation and precise positioning of Si- and SiGe-based
      nanocrystals by templated solid-state dewetting of thin silicon films. The
      dewetting dynamics is guided by pattern size and shape taking full control over
      number, size, shape, and relative position of the particles (islands dimensions
      and relative distances are in the hundreds nm range and fluctuate ~11% for the
      volumes and ~5% for the positioning).

PMID- 27717243
TI  - Differences in gene mutations between Chinese and Caucasian cystic fibrosis
      patients.
AB  - Cystic fibrosis (CF) is rarely seen in Asian populations. We diagnosed two CF
      cases. One of them had a novel mutation c.870-1G>C in the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene. There have been 38 Chinese CF
      patients reported in literature from 1974 until the present (2016), 25 different
      mutations were identified. Only one of these mutations (R553X) is in the
      Caucasian CF screening panel. The mutations identified in Chinese CF patients are
      very different from the common Caucasian gene mutations. The CFTR gene mutation
      spectrum for the Chinese population requires further investigation. Pediatr
      Pulmonol. 2017;52:E11-E14. (c) 2016 The Authors. Pediatric Pulmonology Published
      by Wiley Periodicals, Inc.

PMID- 27717241
TI  - Characterization of a caveolin-1 mutation associated with both pulmonary arterial
      hypertension and congenital generalized lipodystrophy.
AB  - Congenital generalized lipodystrophy (CGL) and pulmonary arterial hypertension
      (PAH) have recently been associated with mutations in the caveolin-1 ( CAV1 )
      gene, which encodes the primary structural protein of caveolae. However, little
      is currently known about how these CAV1 mutations impact caveolae formation or
      contribute to the development of disease. Here, we identify a heterozygous F160X
      CAV1 mutation predicted to generate a C-terminally truncated mutant protein in a
      patient with both PAH and CGL using whole exome sequencing, and characterize the
      properties of CAV1 , caveolae-associated proteins and caveolae in skin
      fibroblasts isolated from the patient. We show that morphologically defined
      caveolae are present in patient fibroblasts and that they function in
      mechanoprotection. However, they exhibited several notable defects, including
      enhanced accessibility of the C-terminus of wild-type CAV1 in caveolae, reduced
      colocalization of cavin-1 with CAV1 and decreased stability of both 8S and 70S
      oligomeric CAV1 complexes that are necessary for caveolae formation. These
      results were verified independently in reconstituted CAV1 -/- mouse embryonic
      fibroblasts. These findings identify defects in caveolae that may serve as
      contributing factors to the development of PAH and CGL and broaden our knowledge
      of CAV1 mutations associated with human disease.

PMID- 27717244
TI  - Telomere content measurement in human hematopoietic cells: Comparative analysis
      of qPCR and Flow-FISH techniques.
AB  - Abnormal telomere lengths have been linked to cancer and other hematologic
      disorders. Determination of mean telomere content (MTC) is traditionally
      performed by Southern blotting and densitometry, giving a mean telomere
      restriction fragment (TRF) value for the total cell population studied. Here, we
      compared a quantitative Polymerase Chain Reaction approach (qPCR) and a flow
      cytometric approach, fluorescence in situ hybridization (Flow-FISH), to evaluate
      telomere content distribution in total patient peripheral blood mononuclear cells
      or specific cell populations. Flow-FISH is based on in situ hybridization using a
      fluorescein-labeled peptide nucleic acid (PNA) (CCCTAA)3 probe and DNA staining
      with propidium iodide. We showed that both qPCR and Flow-FISH provide a robust
      measurement, with Flow-FISH measuring a relative content longer than qPCR at a
      single cell approach and that TRF2 fluorescence intensity did not correlate with
      MTC. Both methods showed comparable telomere content reduction with age, and the
      rate of relative telomere loss was similar. Published 2016 Wiley Periodicals Inc.
      This article is a US government work and, as such, is in the public domain in the
      United States of America.

PMID- 27717245
TI  - tipdatingbeast: an r package to assist the implementation of phylogenetic tip
      dating tests using beast.
AB  - Molecular tip dating of phylogenetic trees is a growing discipline that uses DNA
      sequences sampled at different points in time to coestimate the timing of
      evolutionary events with rates of molecular evolution. In this context, beast, a
      program for Bayesian analysis of molecular sequences, is the most widely used
      phylogenetic tool. Here, we introduce tipdatingbeast, an r package built to
      assist the implementation of various phylogenetic tip-dating tests using beast.
      tipdatingbeast currently contains two main functions. The first one allows
      preparing date-randomization analyses, which assess the temporal signal of a data
      set. The second function allows performing leave-one-out analyses, which test for
      the consistency between independent calibration sequences and allow pinpointing
      those leading to potential bias. We apply those functions to an empirical data
      set and supply practical guidance for results interpretation.

PMID- 27717246
TI  - Exercise-induced inspiratory symptoms in school children.
AB  - BACKGROUND AND AIMS: Exercise-induced inspiratory symptoms (EIIS) have multiple
      causes, one of which is exercise-induced laryngeal obstruction (EILO). There is
      limited knowledge regarding EIIS in children, both in primary care practices and
      in pediatric asthma clinics. The aim of this study was to describe the
      feasibility of a diagnostic methodology and its results in a cohort of children
      with EIIS referred to our tertiary pediatric pulmonary center. METHODS: This
      study analyzed consecutively collected data in children from East Denmark and
      Greater Copenhagen referred during a 31/2 years period. The continuous
      laryngoscopy exercise (CLE) test directly visualizes the larynx using a flexible
      laryngoscope during a maximal exercise test. A post-test questionnaire evaluated
      the subjective impact of the examination. RESULTS: The study included 60 children
      (37 girls/23 boys) with a mean age of 14 years (range 9-18). The feasibility of
      the CLE test was 98%; 18 children (35%) had EILO, while 33 children (61%) showed
      no abnormalities. Other laryngeal abnormalities were observed in three children
      before the exercise test. Asthma medication was successfully discontinued in 13
      (72%) children with EILO. A significantly greater proportion of children shown to
      have EILO in the CLE test reported coping better with their EIIS than children
      with negative test (85% vs. 45%; P = 0.03). CONCLUSIONS: Continuous laryngoscopy
      during exercise is feasible and useful for identifying children with EILO. A
      correct diagnosis of EILO can help relieve patient anxiety, improve their coping
      with symptoms, and prevent unnecessary long-term and potentially harmful asthma
      treatments involving high-dose inhaled steroids. Pediatr Pulmonol. 2016;51:1200
      1205. (c) 2016 Wiley Periodicals, Inc.

PMID- 27717248
TI  - Editorial.

PMID- 27717247
TI  - Comparative transcriptomics reveal host-specific nucleotide variation in
      entomophthoralean fungi.
AB  - Obligate parasites are under strong selection to increase exploitation of their
      host to survive while evading detection by host immune defences. This has often
      led to elaborate pathogen adaptations and extreme host specificity.
      Specialization on one host, however, often incurs a trade-off influencing the
      capacity to infect alternate hosts. Here, we investigate host adaptation in two
      morphologically indistinguishable and closely related obligate specialist insect
      pathogenic fungi from the phylum Entomophthoromycota, Entomophthora muscae sensu
      stricto and E. muscae sensu lato, pathogens of houseflies (Musca domestica) and
      cabbage flies (Delia radicum), respectively. We compared single nucleotide
      polymorphisms within and between these two E. muscae species using 12 RNA-seq
      transcriptomes from five biological samples. All five isolates contained intra
      isolate polymorphisms that segregate in 50:50 ratios, indicative of genetic
      duplication events or functional diploidy. Comparative analysis of dN/dS ratios
      between the multinucleate E. muscae s.str. and E. muscae s.l. revealed molecular
      signatures of positive selection in transcripts related to utilization of host
      lipids and the potential secretion of toxins that interfere with the host immune
      response. Phylogenetic comparison with the nonobligate generalist insect
      pathogenic fungus Conidiobolus coronatus revealed a gene-family expansion of
      trehalase enzymes in E. muscae. The main sugar in insect haemolymph is trehalose,
      and efficient sugar utilization was probably important for the evolutionary
      transition to obligate insect pathogenicity in E. muscae. These results support
      the hypothesis that genetically based host specialization in specialist pathogens
      evolves in response to the challenge of using resources and dealing with the
      immune system of different hosts.

PMID- 27717249
TI  - Improving education, policy and research in mental health worldwide: the role of
      the WPA Collaborating Centres.

PMID- 27717250
TI  - Right patient, right treatment, right time: biosignatures and precision medicine
      in depression.

PMID- 27717251
TI  - Adopting a continuous improvement model for future DSM revisions.

PMID- 27717252
TI  - Bodily distress disorder in ICD-11: problems and prospects.

PMID- 27717253
TI  - Pragmatic treatment options for depression and anxiety disorders are needed.

PMID- 27717255
TI  - The four basic components of psychoanalytic technique and derived psychoanalytic
      psychotherapies.

PMID- 27717256
TI  - Psychodynamic therapy of obsessive-compulsive disorder: principles of a manual
      guided approach.

PMID- 27717257
TI  - Narrowing the gap between ICD/DSM and RDoC constructs: possible steps and
      caveats.

PMID- 27717259
TI  - Mindfulness-based cognitive therapy for relapse prophylaxis in mood disorders.

PMID- 27717260
TI  - Person-centered measurement-based care for depression.

PMID- 27717254
TI  - How effective are cognitive behavior therapies for major depression and anxiety
      disorders? A meta-analytic update of the evidence.
AB  - We report the current best estimate of the effects of cognitive behavior therapy
      (CBT) in the treatment of major depression (MDD), generalized anxiety disorder
      (GAD), panic disorder (PAD) and social anxiety disorder (SAD), taking into
      account publication bias, the quality of trials, and the influence of waiting
      list control groups on the outcomes. In our meta-analyses, we included randomized
      trials comparing CBT with a control condition (waiting list, care-as-usual or
      pill placebo) in the acute treatment of MDD, GAD, PAD or SAD, diagnosed on the
      basis of a structured interview. We found that the overall effects in the 144
      included trials (184 comparisons) for all four disorders were large, ranging from
      g=0.75 for MDD to g=0.80 for GAD, g=0.81 for PAD, and g=0.88 for SAD. Publication
      bias mostly affected the outcomes of CBT in GAD (adjusted g=0.59) and MDD
      (adjusted g=0.65), but not those in PAD and SAD. Only 17.4% of the included
      trials were considered to be high-quality, and this mostly affected the outcomes
      for PAD (g=0.61) and SAD (g=0.76). More than 80% of trials in anxiety disorders
      used waiting list control groups, and the few studies using other control groups
      pointed at much smaller effect sizes for CBT. We conclude that CBT is probably
      effective in the treatment of MDD, GAD, PAD and SAD; that the effects are large
      when the control condition is waiting list, but small to moderate when it is care
      as-usual or pill placebo; and that, because of the small number of high-quality
      trials, these effects are still uncertain and should be considered with caution.

PMID- 27717261
TI  - Updating the Research Domain Criteria.

PMID- 27717263
TI  - Alarming increase of suicide in a remote Indigenous Australian population: an
      audit of data from 2005 to 2014.

PMID- 27717262
TI  - Abandoning personalization to get to precision in the pharmacotherapy of
      depression.
AB  - Effectiveness studies and analyses of naturalistic cohorts demonstrate that many
      patients with major depressive disorder do not experience symptomatic remission
      with antidepressant treatments. In an effort to better match patients with
      effective treatments, numerous investigations of predictors or moderators of
      treatment response have been reported over the past five decades, including
      clinical features as well as biological measures. However, none of these have
      entered routine clinical practice; instead, clinicians typically personalize
      treatment on the basis of patient preferences as well as their own. Here, we
      review the reasons why it has been challenging to identify and deploy treatment
      specific predictors of response, and suggest strategies that may be required to
      achieve true precision in the pharmacotherapy of depression. We emphasize the
      need for changes in how depression care is delivered, measured, and used to
      inform future practice.

PMID- 27717264
TI  - Carving depression at its joints?

PMID- 27717258
TI  - Traditional marijuana, high-potency cannabis and synthetic cannabinoids:
      increasing risk for psychosis.
AB  - Epidemiological evidence demonstrates that cannabis use is associated with an
      increased risk of psychotic outcomes, and confirms a dose-response relationship
      between the level of use and the risk of later psychosis. High-potency cannabis
      and synthetic cannabinoids carry the greatest risk. Experimental administration
      of tetrahydrocannabinol, the active ingredient of cannabis, induces transient
      psychosis in normal subjects, but this effect can be ameliorated by co
      administration of cannabidiol. This latter is a constituent of traditional
      hashish, but is largely absent from modern high-potency forms of cannabis.
      Argument continues over the extent to which genetic predisposition is correlated
      to, or interacts with, cannabis use, and what proportion of psychosis could be
      prevented by minimizing heavy use. As yet, there is not convincing evidence that
      cannabis use increases risk of other psychiatric disorders, but there are no such
      doubts concerning its detrimental effect on cognitive function. All of the
      negative aspects are magnified if use starts in early adolescence. Irrespective
      of whether use of cannabis is decriminalized or legalized, the evidence that it
      is a component cause of psychosis is now sufficient for public health messages
      outlining the risk, especially of regular use of high-potency cannabis and
      synthetic cannabinoids.

PMID- 27717266
TI  - WPA Position Statement on Gender Identity and Same-Sex Orientation, Attraction
      and Behaviours.

PMID- 27717267
TI  - Functional remediation: the pathway from remission to recovery in bipolar
      disorder.

PMID- 27717268
TI  - Taking the depressed "person" into account before moving into personalized or
      precision medicine.

PMID- 27717265
TI  - Community mental health care worldwide: current status and further developments.
AB  - This paper aims to give an overview of the key issues facing those who are in a
      position to influence the planning and provision of mental health systems, and
      who need to address questions of which staff, services and sectors to invest in,
      and for which patients. The paper considers in turn: a) definitions of community
      mental health care; b) a conceptual framework to use when evaluating the need for
      hospital and community mental health care; c) the potential for wider platforms,
      outside the health service, for mental health improvement, including schools and
      the workplace; d) data on how far community mental health services have been
      developed across different regions of the world; e) the need to develop in more
      detail models of community mental health services for low- and middle-income
      countries which are directly based upon evidence for those countries; f) how to
      incorporate mental health practice within integrated models to identify and treat
      people with comorbid long-term conditions; g) possible adverse effects of
      deinstitutionalization. We then present a series of ten recommendations for the
      future strengthening of health systems to support and treat people with mental
      illness.

PMID- 27717269
TI  - Pathological gambling: a behavioral addiction.

PMID- 27717270
TI  - Rising suicide rates: an under-recognized role for the Internet?

PMID- 27717271
TI  - Self-Help Plus (SH+): a new WHO stress management package.

PMID- 27717272
TI  - Can we at least learn to fail faster?

PMID- 27717273
TI  - "Prolonged grief disorder" and "persistent complex bereavement disorder", but not
      "complicated grief", are one and the same diagnostic entity: an analysis of data
      from the Yale Bereavement Study.
AB  - There exists a general consensus that prolonged grief disorder (PGD), or some
      variant of PGD, represents a distinct mental disorder worthy of diagnosis and
      treatment. Nevertheless, confusion remains over whether different names and
      proposed symptom criteria for this disorder identify the same or different
      diagnostic entities. This study aimed to determine whether PGD, complicated grief
      (CG), and persistent complex bereavement disorder (PCBD) as described by the DSM
      5 are substantively or merely semantically different diagnostic entities. Data
      were derived from the Yale Bereavement Study, a longitudinal community-based
      study of bereaved individuals funded by the US National Institute of Mental
      Health, designed explicitly to evaluate diagnostic criteria for disordered grief.
      The results suggested that the difference between PGD and PCBD is only semantic.
      The level of agreement between the original PGD test, a new version of the PGD
      test proposed for ICD-11 and the PCBD test was high (pairwise kappa coefficients
      = 0.80-0.84). Their estimates of rate of disorder in this community sample were
      similarly low (~10%). Their levels of diagnostic specificity were comparably high
      (95.0-98.3%). Their predictive validity was comparable. In contrast, the test for
      CG had only moderate agreement with those for PGD and PCBD; its estimate of rate
      of disorder was three-fold higher (~30%); its diagnostic specificity was poorer,
      and it had no predictive validity. We conclude that PGD, PCBD and proposed ICD
      11, but not CG, symptom-diagnostic tests identify a single diagnostic entity.
      Ultimately, brief symptom-diagnostic tests, such as the one proposed here for ICD
      11, may have the greatest clinical utility.

PMID- 27717274
TI  - Prescribing according to diagnosis: how psychiatry is different.

PMID- 27717276
TI  - Toward precision medicine for depression: admitting ignorance and focusing on
      failures.

PMID- 27717275
TI  - Disorders related to sexuality and gender identity in the ICD-11: revising the
      ICD-10 classification based on current scientific evidence, best clinical
      practices, and human rights considerations.
AB  - In the World Health Organization's forthcoming eleventh revision of the
      International Classification of Diseases and Related Health Problems (ICD-11),
      substantial changes have been proposed to the ICD-10 classification of mental and
      behavioural disorders related to sexuality and gender identity. These concern the
      following ICD-10 disorder groupings: F52 Sexual dysfunctions, not caused by
      organic disorder or disease; F64 Gender identity disorders; F65 Disorders of
      sexual preference; and F66 Psychological and behavioural disorders associated
      with sexual development and orientation. Changes have been proposed based on
      advances in research and clinical practice, and major shifts in social attitudes
      and in relevant policies, laws, and human rights standards. This paper describes
      the main recommended changes, the rationale and evidence considered, and
      important differences from the DSM-5. An integrated classification of sexual
      dysfunctions has been proposed for a new chapter on Conditions Related to Sexual
      Health, overcoming the mind/body separation that is inherent in ICD-10. Gender
      identity disorders in ICD-10 have been reconceptualized as Gender incongruence,
      and also proposed to be moved to the new chapter on sexual health. The proposed
      classification of Paraphilic disorders distinguishes between conditions that are
      relevant to public health and clinical psychopathology and those that merely
      reflect private behaviour. ICD-10 categories related to sexual orientation have
      been recommended for deletion from the ICD-11.

PMID- 27717278
TI  - The social defeat hypothesis of schizophrenia: issues of measurement and reverse
      causality.

PMID- 27717277
TI  - Ultra high risk status and transition to psychosis in 22q11.2 deletion syndrome.
AB  - The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of
      psychotic symptoms and schizophrenia, making this condition a promising human
      model for studying risk factors for psychosis. We explored the predictive value
      of ultra high risk (UHR) criteria in a sample of patients with 22q11DS. We also
      examined the additional contribution of socio-demographic, clinical and cognitive
      variables to predict transition to psychosis within a mean interval of 32.5 +/-
      17.6 months after initial assessment. Eighty-nine participants with 22q11DS (age
      range: 8-30 years; mean 16.1 +/- 4.7) were assessed using the Structured
      Interview for Psychosis-Risk Syndromes. Information on Axis I diagnoses,
      internalizing and externalizing symptoms, level of functioning and IQ was also
      collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to
      those without a UHR condition, they had a significantly lower functioning, more
      frequent anxiety disorders, and more severe psychopathology. Transition rate to
      psychosis was 27.3% in UHR and 4.5% in non-UHR participants. Cox regression
      analyses revealed that UHR status significantly predicted conversion to
      psychosis. Baseline level of functioning was the only other additional predictor.
      This is the first study investigating the predictive value of UHR criteria in
      22q11DS. It indicates that the clinical path leading to psychosis is broadly
      comparable to that observed in other clinical high-risk samples. Nevertheless,
      the relatively high transition rate in non-UHR individuals suggests that other
      risk markers should be explored in this population. The role of low functioning
      as a predictor of transition to psychosis should also be investigated more in
      depth.

PMID- 27717279
TI  - Successful renal retransplantation after graft loss from BK polyomavirus
      infection in a human immunodeficiency virus-positive patient.
AB  - We report the case of a human immunodeficiency virus-seropositive patient whose
      initial kidney transplant failed because of BK polyomavirus-induced nephropathy,
      and who underwent a second transplantation 3 years later. BK viruria was detected
      1 day after transplantation. After 1 month, BK viremia developed along with a
      donor-specific antibody. After decreasing tacrolimus and mycophenolic acid and 2
      courses of intravenous immunoglobulins, BK viremia and donor-specific antibody
      permanently disappeared, with stable renal function.

PMID- 27717280
TI  - Evaluation of fibronectin 1 in one dried blood spot and in urine after rhGH
      treatment.
AB  - Since the appearance of recombinant human growth hormone (rhGH) in the 1980s, its
      expansion and acquisition through the black market has increased, so the
      detection of its abuse continues to be a challenge. New biomarkers that are more
      reliable and sensitive, allowing a larger detection window, are still needed. In
      this line, Fibronectin 1 (FN1) has been proposed as a potential genetic and
      protein biomarker of rhGH abuse in peripheral blood lymphocytes, serum, and
      plasma. However, logistic problems associated with current blood collection in
      sports drug testing point towards potential new alternative matrices that could
      be good candidates to be evaluated. Results obtained in this study showed high
      ELISA FN1 levels in one dried blood spot and in urine samples in ten healthy male
      volunteers treated with rhGH. Results showed that especially dried blood spots
      appear as a potential good matrix to detect rhGH abuse by means of FN1 biomarker.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27717281
TI  - Computed Tomography-Guided Percutaneously Controlled Ablation of the Thoracic
      Paravertebral Nerve Due to Thoracic Neuropathic Pain.
AB  - BACKGROUND: Patients with thoracic neuropathic pain often do not respond to
      medication and physical therapy. Coblation technology has been demonstrated to
      have potential for pain management. METHODS: Fifteen patients underwent computed
      tomography-guided percutaneous coblation to ablate the thoracic paravertebral
      nerve for their medication-resistant thoracic neuropathic pain. The pain
      intensity was assessed by visual analog scale (VAS) 1 day before surgery and 1
      week and 1, 3, and 6 months after surgery, and the difference between
      preoperative and postoperative VAS values was determined to evaluate the pain
      relief effectiveness. Patients who achieved > 50% pain relief were defined as
      responders, and the ratio in all patients was calculated. The number of patients
      who reported mild pain (VAS <= 3) was recorded, and the ratio in all responders
      was calculated. In addition, adverse effects were also recorded to investigate
      the security of procedure. RESULTS: Twelve (80%) responders achieved > 50% pain
      relief. The VAS score of responders significantly decreased from 7.42 +/- 1.38
      before surgery to 2.17 +/- 1.11 (P = 0.000), 1.92 +/- 1.16 (P = 0.000), 1.75 +/-
      0.97 (P = 0.000), and 1.58 +/- 1.08 (P = 0.000) at 1 week, 1, 3, and 6 months
      after surgery, respectively. The number of responders with mild pain was 10
      (83.3%), 11 (91.7%), 12 (100%), and 12 (100%) at 1 week, 1, 3, and 6 months after
      surgery, respectively. All responders and 1 nonresponder reported slight numbness
      after the surgery. CONCLUSION: Percutaneous thoracic paravertebral nerve
      coblation guided by computed tomography is a potential method for the treatment
      of thoracic neuropathic pain.

PMID- 27717282
TI  - Multi-Responsive "Turn-On" Nanocarriers for Efficient Site-Specific Gene Delivery
      In Vitro and In Vivo.
AB  - Systemic gene delivery is a complicated and multistep process that confronts
      numerous biological barriers. It remains a formidable challenge to exploit a
      single gene carrier with multiple features to combat all obstacles collectively.
      Herein, a multi-responsive "turn-on" polyelectrolyte complex (DNA/OEI-SSx /HA-SS
      COOH, DSS) delivery system is demonstrated with a sequential self-assembly of
      disulfide-conjugated oligoethylenimine (OEI-SSx ) and disulfide bond-modified
      hyaluronic acid envelope (HA-SS-COOH) that can combat multiple biological
      barriers collectively when administered intravenously. DSS is designed to
      effectively accumulate at the tumor tissue and to be internalized into tumor
      cells by recognizing CD44. The multi-responsive "turn-on" DSS can respond to the
      alterations of hyaluronidases and glutathione at both the tumor site and at the
      intracellular milieu. Sequential degradation and detachment of the HA-SS-COOH
      envelope followed by the dissociation of the OEI-SSx/DNA inner core contributes
      to the activation of the endosomal escape and gene release functions, thus
      greatly enhancing nuclear gene delivery. A systematic investigation of DSS has
      revealed that the tumor accumulation ability, internalization, and endosome
      escape of the DSS nanocarriers, DNA unpacking and nuclear transportation are all
      remarkably improved by the multi-responsive "turn-on" design resulting in highly
      efficient gene transfection in vitro and in vivo.

PMID- 27717285
TI  - Barrierless Switching Between a Liquid and Superheated Solid Catalyst During
      Nanowire Growth.
AB  - Knowledge of nucleation and growth mechanisms is essential for the synthesis of
      nanomaterials, such as semiconductor nanowires, with shapes and compositions
      precisely engineered for technological applications. Nanowires are conventionally
      grown by the seemingly well-understood vapor-liquid-solid mechanism, which uses a
      liquid alloy as the catalyst for growth. However, we show that it is possible to
      instantaneously and reversibly switch the phase of the catalyst between a liquid
      and superheated solid state under isothermal conditions above the eutectic
      temperature. The solid catalyst induces a vapor-solid-solid growth mechanism,
      which provides atomic-level control of dopant atoms in the nanowire. The
      switching effect cannot be predicted from equilibrium phase diagrams but can be
      explained by the dominant role of the catalyst surface in modulating the kinetics
      and thermodynamics of phase behavior. The effect should be general to metal
      catalyzed nanowire growth and highlights the unexpected yet technologically
      relevant non-equilibrium effects that can emerge in the growth of nanoscale
      systems.

PMID- 27717283
TI  - Proteomic and phosphoproteomic analyses of yeast reveal the global cellular
      response to sphingolipid depletion.
AB  - Sphingolipids are essential components of eukaryotic cells with important
      functions in membrane biology and cellular signaling. Their levels are tightly
      controlled and coordinated with the abundance of other membrane lipids. How
      sphingolipid homeostasis is achieved is not yet well understood. Studies
      performed primarily in yeast showed that the phosphorylation states of several
      enzymes and regulators of sphingolipid synthesis are important, although a global
      understanding for such regulation is lacking. Here, we used high-resolution MS
      based proteomics and phosphoproteomics to analyze the cellular response to
      sphingolipid synthesis inhibition. Our dataset reveals that changes in protein
      phosphorylation, rather than protein abundance, dominate the response to blocking
      sphingolipid synthesis. We identified Ypk signaling as a pathway likely to be
      activated under these conditions, and we identified potential Ypk1 target
      proteins. Our data provide a rich resource for on-going mechanistic studies of
      key elements of the cellular response to the depletion of sphingolipid levels and
      the maintenance of sphingolipid homeostasis. All MS data have been deposited in
      the ProteomeXchange with identifier PXD003854
      (http://proteomecentral.proteomexchange.org/dataset/PXD003854).

PMID- 27717284
TI  - Young investigator challenge: The morphologic analysis of noninvasive follicular
      thyroid neoplasm with papillary-like nuclear features on liquid-based cytology:
      Some insights into their identification.
AB  - BACKGROUND: Noninvasive follicular thyroid neoplasm with papillary-like nuclear
      features (NIFTP) represents a challenge for the diagnosis and management of
      thyroid carcinoma. Some authors have proposed histological criteria that are able
      to distinguish NIFTPs from invasive follicular variant of papillary thyroid
      carcinoma (I-FVPTC). Hence, NIFTPs may have repercussions in the diagnostic
      categories on fine-needle aspiration. In the current study, the authors evaluated
      the criteria for NIFTPs on liquid-based cytology samples. METHODS: The authors
      recorded all 61 liquid-based cytology samples proved to be histological FVPTC
      between January 2013 and March 2016 and analyzed the architectural, cytoplasmic,
      and nuclear parameters. They compared them with a cohort of 40 PTC cases and 20
      follicular adenoma cases. RESULTS: The authors reported 37 NIFTP cases and 24 I
      FVPTC cases at histology. The cytological diagnoses of follicular nodules in the
      NIFTP cases were twice those found in the I-FVPTC cases (54.1% vs 29.2%). The
      number of positive for malignancy cases among the NIFTPs were approximately half
      those of I-FVPTC cases. When compared with I-FVPTCs, 70% of the NIFTP cases
      demonstrated a nuclear size <20 MUm (P = .025) and rarely exhibited grooves (13%
      vs 42%; P = .009). The authors found 100% of cases with wild-type BRAF gene in
      NIFTP cases versus 38.4% in mutated I-FVPTC cases (P = .046). The cytoplasmic
      features might help to discriminate NIFTPs from follicular adenomas but not from
      I-FVPTCs (P>.05). A predominant microfollicular pattern was recognized in both
      NIFTPs and I-FVPTCs (97.3% vs 100%). CONCLUSIONS: The majority of NIFTPs appear
      to be devoid of nuclear pseudoinclusions and papillary structures, thereby
      allowing the inclusion in the follicular nodule cases. Nuclear size and
      microfollicular clusters may suggest the discrimination between NIFTPs and I
      FVPCs. Cancer Cytopathol 2016;124:699-710. (c) 2016 American Cancer Society.

PMID- 27717286
TI  - Combination of Liquid Chromatography with Multivariate Curve Resolution
      Alternating Least-Squares (MCR-ALS) in the Quantitation of Polycyclic Aromatic
      Hydrocarbons Present in Paprika Samples.
AB  - This work presents a strategy for quantitating polycyclic aromatic hydrocarbons
      (PAHs) in smoked paprika samples. For this, a liquid chromatographic method with
      fluorimetric detection (HPLC-FLD) was optimized. To resolve some interference co
      eluting with the target analytes, the second-order multivariate curve resolution
      alternating least-squares (MCR-ALS) algorithm has been employed combined with
      this liquid chromatographic method. Among the eight PAHs quantified (fluorene,
      phenanthrene, anthracene, pyrene, chrysene, benzo[a]anthracene,
      benzo[b]fluoranthene, and benzo[a]pyrene) by HPLC-FLD, only in the case of
      fluorene, pyrene, and benzo[b]fluoranthene was it necessary to apply the second
      order algorithm for their resolution. Limits of detection and quantitation were
      between 0.015 and 0.45 mg/kg and between 0.15 and 1.5 mg/kg, respectively. Good
      recovery results (>80%) for paprika were obtained via the complete extraction
      procedure, consisting of an extraction from the matrix and the cleanup of the
      extract by means of silica cartridges. Higher concentrations of chrysene,
      benzo[a]anthracene, benzo[b]fluoranthene, and benzo[a]pyrene were found in the
      paprika samples, with respect to the maximal amounts allowed for other spices
      that are under European Regulation (EU) N degrees  2015/1933.

PMID- 27717287
TI  - Cocaine Vaccine Development: Evaluation of Carrier and Adjuvant Combinations That
      Activate Multiple Toll-Like Receptors.
AB  - Although cocaine abuse and addiction continue to cause serious health and
      societal problems, an FDA-approved medication to treat cocaine addiction has yet
      to be developed. Employing a pharmacokinetic strategy, an anticocaine vaccine
      provides an attractive avenue to address these issues; however, current vaccines
      have shown varying degrees of efficacy, indicating that further formulation is
      necessary. As a means to improve vaccine efficacy, we examined the effects of
      varying anticocaine vaccine formulations by combining a Toll-like receptor 9
      (TLR9) agonist with a TLR5 agonist in the presence of alum. The TLR9 agonist used
      was cytosine-guanine oligodeoxynucleotide 1826 (CpG 1826), while the TLR5 agonist
      was flagellin (FliC). Formulations with the TLR9 agonist elicited superior
      anticocaine antibody titers and blockade of hyperlocomotor effects compared to
      vaccines without CpG 1826. This improvement was seen regardless of whether the
      TLR5 agonist, FliC, or the nonadjuvanting Tetanus Toxoid (TT) was used as the
      carrier protein. Additional insights into the value of FliC as a carrier versus
      adjuvant was also investigated by generating two unique formats of the protein,
      wild-type and mutated flagellin (mFliC). While the mFliC conjugate retained its
      ability to stimulate mTLR5, it yielded reduced cocaine sequestration and
      functional blockade relative to FliC and TT. Overall, this work indicates that
      activation of TLR9 can improve the function of cocaine vaccines in the presence
      of TLR5 activation by FliC, with any potential additive effects limited by the
      inefficiency of FliC as a carrier protein as compared to TT.

PMID- 27717288
TI  - Influence of Chirality of Lactones on the Perception of Some Typical Fruity Notes
      through Perceptual Interaction Phenomena in Bordeaux Dessert Wines.
AB  - Recent studies concerning the aroma of noble rot dessert wines revealed the
      importance of a well-known phenomenon in perfumery, the perceptual blending, to
      create the perception of "overripe orange" nuances. Thus, compounds associated
      with both oak wood aging (3-methyl-4-octanolide and eugenol) and Botrytis cinerea
      development under the form of noble rot (2-nonen-4-olide and gamma-nonalactone)
      contribute to a specific aroma of great noble rot dessert wines through
      perceptual interaction phenomena. This synthetic perception phenomenon was
      established from reconstitution, addition, and omission sensory experiments,
      using wine extract fractions supplemented with the volatile compounds previously
      mentioned. To better understand the sensory impact of these compounds, the goal
      of this research was to study the contributions of enantiomeric forms of 2-nonen
      4-olide and gamma-nonalactone and the diastereoisomers of 3-methyl-4-octanolide.
      After multidimensional chiral chromatography analysis, the relative proportions
      of enantiomers or diastereomeric forms were first established and then sensory
      experiments were carried out using the reference compounds with isolated
      fractions from dessert wines. A dominance of the R form was established for 2
      nonen-4-olide, which was correlated with wine aging, while the S form is more
      dominant in young dessert wines. Furthermore, the reconstitution experiments
      confirmed perceptual interaction phenomena and revealed the sensory contribution
      of (R)-2-nonen-4-olide and cis-3-methyl-4-octanolide concerning the "overripe
      orange" nuances, whereas no sensory impact for the gamma-nonalactone isomers was
      observed.

PMID- 27717289
TI  - Response of growing goslings to dietary supplementation with methionine and
      betaine.
AB  - An experiment with a 2 * 3 factorial design with two concentrations of dietary
      betaine (0 and 600 mg/kg) and three dietary concentrations of methionine (0, 600
      and 1200 mg/kg) was conducted using goslings to estimate growth, nutrient
      utilisation and digestibility of amino acids from 21 to 70 d of age. Three
      hundred geese were randomised at 18 d of age into 6 groups with 5 replicates per
      treatment and 10 geese per replicate. Increasing dietary concentrations of
      methionine gave a linear increase in body weight and average daily gain. The
      coefficient of crude fat retention increased as dietary methionine increased and
      there was a significant non-linear response to increasing dietary methionine.
      Similarly, increasing supplemental methionine gave linear increases in the
      digestibility of methionine and cysteine. The results of this study indicated
      that optimal dietary supplementation of methionine could increase growth
      performance and methionine and cysteine utilisation in growing goslings. Betaine
      supplementation had no apparent sparing effect on methionine needs for growth
      performance, but did improve the apparent cysteine digestibility.

PMID- 27717290
TI  - Mycotoxin in the food supply chain-implications for public health program.
AB  - Mycotoxins are a group of naturally occurring toxic chemical substances, produced
      mainly by microscopic filamentous fungal species. Regarding potential synergisms
      or even mitigating effects between toxic elements, mycotoxin contamination will
      continue to be an area of concern for producers, manufacturers, regulatory
      agencies, researchers, and consumers in the future. In Serbia, recent drought and
      then flooding confirmed that mycotoxins are one of the foodborne hazards most
      susceptible to climate change. In this article, we review key aspects of
      mycotoxin contamination of the food supply chain and implications for public
      health from the Serbian perspective.

PMID- 27717291
TI  - Turbulent eddy diffusion models in exposure assessment - Determination of the
      eddy diffusion coefficient.
AB  - The use of the turbulent eddy diffusion model and its variants in exposure
      assessment is limited due to the lack of knowledge regarding the isotropic eddy
      diffusion coefficient, DT. But some studies have suggested a possible
      relationship between DT and the air changes per hour (ACH) through a room. The
      main goal of this study was to accurately estimate DT for a range of ACH values
      by minimizing the difference between the concentrations measured and predicted by
      eddy diffusion model. We constructed an experimental chamber with a spatial
      concentration gradient away from the contaminant source, and conducted 27 3-hr
      long experiments using toluene and acetone under different air flow conditions
      (0.43-2.89 ACHs). An eddy diffusion model accounting for chamber boundary,
      general ventilation, and advection was developed. A mathematical expression for
      the slope based on the geometrical parameters of the ventilation system was also
      derived. There is a strong linear relationship between DT and ACH, providing a
      surrogate parameter for estimating DT in real-life settings. For the first time,
      a mathematical expression for the relationship between DT and ACH has been
      derived that also corrects for non-ideal conditions, and the calculated value of
      the slope between these two parameters is very close to the experimentally
      determined value. The values of DT obtained from the experiments are generally
      consistent with values reported in the literature. They are also independent of
      averaging time of measurements, allowing for comparison of values obtained from
      different measurement settings. These findings make the use of turbulent eddy
      diffusion models for exposure assessment in workplace/indoor environments more
      practical.

PMID- 27717292
TI  - Reduction in ulnar pressure distribution when walking with forearm crutches with
      a novel cuff design: Cross-sectional intervention study on the biomechanical
      efficacy of an ulnar recess.
AB  - Walking with crutches is an effective way of reducing the load on the lower
      extremity and is often indicated after injury or surgery. However, walking with
      forearm crutches with conventional cuffs can trigger symptoms including
      tenosynovitis in the biceps tendon, ulnar neuropraxia at the wrist, pain, or skin
      hematoma. The purpose of this study was to test the hypothesis that a crutch cuff
      design with an ulnar recess reduces ulnar pressure during walking with forearm
      crutches. The pressure distribution between the forearm and crutch cuff was
      measured in 15 healthy participants for crutch walking with conventional and
      novel cuffs, respectively. Relative peak pressure in the proximal medial region
      compared to the overall peak pressure was reduced by 8.6% when walking with
      crutches with the novel cuff design compared to conventional cuffs (p < 0.001).
      Relative peak pressure in the distal intermediate and lateral regions were
      increased by 3.3% and 3.7% for the novel compared with conventional cuffs,
      respectively (p < 0.001 for both). Hence, the novel crutch cuffs shifted regions
      of high pressure away from the proximal ulnar region towards more distal regions
      that are covered by more soft tissue.

PMID- 27717293
TI  - Is One Early Renographic Follow-Up Adequate to Measure the Success of Robotic
      Pyeloplasty?
AB  - PURPOSE: Diuretic renography (DRG) is commonly used to diagnose ureteropelvic
      junction obstruction (UPJO) and to evaluate the success of surgical repair
      (pyeloplasty). Duration, frequency, and interpretation of renographic follow-ups
      are still under dispute. METHODS: We retrospectively reviewed 94 consecutive
      patients diagnosed with UPJO who underwent a minimally invasive, robotically
      assisted laparoscopic pyeloplasty at our institution between January 2009 and
      September 2015. DRG was carried out preoperatively and again routinely 4 to 6
      weeks postoperatively the day after stent removal (early DRG). Patients were
      scheduled for repeat (late) DRG and follow-up examinations, including clinical
      status and ultrasonography. RESULTS: Nineteen patients with missing preoperative
      DRG were excluded from the study; the remaining 75 patients were eligible for
      statistical evaluation. At follow-up, 98.7% reported no or only very mild and
      rare symptoms. On early DRG, 52.5% had T1/2 <= 10 min (unobstructed), 39.3% had
      T1/2 between 10 and 20 minutes (equivocal), and 8.2% had T1/2 <= 20 minutes
      (obstructed). At late follow-up, the DRG results had improved to 80.8%
      unobstructed with 19.2% remaining equivocal, and no patients were obstructed;
      thus, the overall success rate was 80.8%. There was only one patient who worsened
      from unobstructed to equivocal from early to late DRG assessment. CONCLUSION: In
      case of complete symptom resolution, a nonobstructive diuretic half-time of <=10
      minutes on early DRG following stent removal suggests that further routine
      renographic follow-up is unnecessary. Patients with an equivocal early DRG (T1/2
      between 10 and 20 minutes) require further scintigraphic follow-up, as they have
      a 42.1% chance of staying equivocal.

PMID- 27717294
TI  - Wastewater and sludge management and research in Oman: An overview.
AB  - : It is well recognized that management of wastewater and sludge is a critical
      environmental issue in many countries. Wastewater treatment and sludge production
      take place under different technical, economic, and social contexts, thus
      requiring different approaches and involving different solutions. In most cases,
      a regular and environmentally safe wastewater treatment and associated sludge
      management requires the development of realistic and enforceable regulations, as
      well as treatment systems appropriate to local circumstances. The main objective
      of this paper is to provide useful information about the current wastewater and
      sludge treatment, management, regulations, and research in Oman. Based on the
      review and discussion, the wastewater treatment and sludge management in Oman has
      been evolving over the years. Further, the land application of sewage sludge
      should encourage revision of existing standards, regulations, and policies for
      the management and beneficial use of sewage sludge in Oman. IMPLICATIONS:
      Wastewater treatment and sludge management in Oman have been evolving over the
      years. Sludge utilization has been a challenge due to its association with human
      waste. Therefore, composting of sewage sludge is the best option in agriculture
      activities. Sludge and wastewater utilization can add up positively in the
      economic aspects of the country in terms of creating jobs and improving annual
      income rate. The number of research projects done on wastewater reuse and other
      ongoing ones related to the land application of sewage sludge should encourage
      revision of existing standards, regulations, and policies for the management and
      beneficial use of sewage sludge in Oman.

PMID- 27717295
TI  - Cognitive Impairment and Mood States after Spinal Cord Injury.
AB  - Spinal cord injury (SCI) is believed to be associated with high rates of
      cognitive impairment, which can result in complications in recovery. This study
      concerned two groups of adults with SCI. The first sample involved 150
      participants with SCI who were assessed once for cognitive capacity with
      comparisons made with 45 able-bodied adults. Sample 2 were drawn from Sample 1,
      and included 88 participants with SCI who were prospectively assessed for mood
      states (anxiety, depressive mood, and fatigue) and pain intensity at three time
      periods: at admission to SCI rehabilitation, at discharge, and 6 months after
      transition into the community. Results showed that the SCI sample had
      significantly lower cognitive performance than the able-bodied control group.
      Further, almost 29% of the adults with SCI had lowered cognitive performance
      believed to be indicative of cognitive impairment. The risk of an adult with SCI
      having cognitive impairment was almost 13 times that of someone without an SCI.
      Results from Sample 2 revealed that the development of negative mood states was a
      significant problem in those with cognitive impairment after they transitioned
      into the community, a time when personal resources are severely challenged.
      Findings suggest all adults with SCI admitted to rehabilitation should receive a
      cognitive screen, and that rehabilitation strategies should then be guided by the
      cognitive performance of the person. Special attention should also be given to
      improving skills of those with cognitive impairment before they transition into
      the community, so as to reduce risk of comorbid mental health problems.

PMID- 27717296
TI  - Cystine Stone Formers Have Impaired Health-Related Quality of Life Compared with
      Noncystine Stone Formers: A Case-Referent Study Piloting the Wisconsin Stone
      Quality of Life Questionnaire Among Patients with Cystine Stones.
AB  - INTRODUCTION: Cystinuria is a rare cause of urolithiasis. Affected patients have
      an earlier onset and more aggressive disease than patients with other stone
      etiologies. We assessed the health-related quality of life (HRQOL) of cystine
      stone-forming patients using the disease-specific Wisconsin Stone Quality of Life
      questionnaire (WISQOL). METHODS: Cystine patients treated in our stone clinics (n
      = 12) completed the WISQOL; information about medical and stone histories was
      gathered. Patients were matched with noncystine stone formers (n = 12) for
      gender, age, and comorbidities. In addition, a second control group (n = 90),
      also from our institution and consisting of mixed calcium stone formers, was
      included. WISQOL responses were compared between groups. RESULTS: Cystine
      patients had significantly lower total WISQOL scores than noncystine patients.
      Compared with noncystine stone formers, cystine stone formers also had lower
      HRQOL scores for subscales (domains) related to social impact, emotional impact,
      disease impact, and vitality (p <= 0.04 for all). On specific items, cystine
      patients reported significantly more sleep problems (p = 0.02), more bother with
      nocturia (p = 0.03), and feeling tired or fatigued (p = 0.02). Among those with
      current stones, cystine patients scored lower than noncystine patients for total
      score and in two of four domains. CONCLUSIONS: Using a stone-specific
      questionnaire, patients with cystine stones have lower HRQOL compared with
      noncystine stone formers. Identifying and addressing specific areas of decrement
      in patients with cystine stones may improve disease management and patients'
      HRQOL.

PMID- 27717297
TI  - Dysphagia progression and feeding skills following pediatric alkali ingestion
      injury: two case reports.
AB  - PURPOSE: There is limited information regarding the nature of dysphagia and
      feeding difficulties following alkali ingestion injury to inform
      multidisciplinary intervention. The aim was to describe the history and nature of
      chronic dysphagia and feeding difficulties in two children following severe
      alkali ingestion injury. METHODS: Medical records, primary caregiver report, and
      clinical assessment were used to compile detailed case histories and assess
      current dysphagia and feeding skills. RESULTS: Both cases demonstrated
      heterogeneous oral motor and feeding outcomes, including delayed oral motor
      skills, restricted dietary variety, and difficult mealtime behaviors that
      contributed to protracted recovery of age-appropriate PO intake. Both children
      required ongoing diet and/or fluid modification and supplemental non-PO feeding
      via gastrostomy at the time of review, that is, 2-year post-injury. CONCLUSIONS:
      Recovery from dysphagia post-alkali ingestion is protracted and complex.
      Dysphagia, delayed oral motor skills, and difficult mealtime behaviors may
      persist secondary to ingestion injury and its associated complications. These
      cases highlight the importance of considering early referral for feeding
      assessment and intervention to assist children and families with recovery.
      Progression through safe and effective oral (per os, PO) intake is needed, as
      well as provision of support for primary caregivers. Implications for
      Rehabilitation Pediatric chemical ingestion injury can cause long-term dysphagia
      and long-term feeding difficulties Initial injury severity does not reliably
      correlate with eventuating level of aerodigestive impairment. Clinical and
      instrumental assessment is required to monitor swallow function to enable
      commencement of targeted rehabilitation when appropriate. Early involvement of a
      feeding therapist is recommended to minimize the long-term effects on oral motor
      skill development, progression to age-appropriate diet, and provision of family
      centered care.

PMID- 27717300
TI  - Comparison of qualitative and quantitative fit-testing results for three commonly
      used respirators in the healthcare sector.
AB  - N95 filtering facepiece respirators are used by healthcare workers when there is
      a risk of exposure to airborne hazards during aerosol-generating procedures.
      Respirator fit-testing is required prior to use to ensure that the selected
      respirator provides an adequate face seal. Two common fit-test methods can be
      employed: qualitative fit-test (QLFT) or quantitative fit-test (QNFT).
      Respiratory protection standards deem both fit-tests to be acceptable. However,
      previous studies have indicated that fit-test results may differ between QLFT and
      QNFT and that the outcomes may also be influenced by the type of respirator
      model. The aim of this study was to determine if there is a difference in fit
      test outcomes with our suite of respirators, 3M - 1860S, 1860, AND 1870, and
      whether the model impacts the fit-test results. Subjects were recruited from
      residential care facilities. Each participant was assigned a respirator and
      underwent sequential QLFT and QNFT fit-tests and the results (either pass or
      fail) were recorded. To ascertain the degree of agreement between the two fit
      tests, a Kappa (Kappa) statistic was conducted as per the American National
      Standards Institute (ANSI) respiratory protection standard. The pass-fail rates
      were stratified by respirator model and a Kappa statistic was calculated for each
      to determine effect of model on fit-test outcomes. We had 619 participants and
      the aggregate Kappa statistic for all respirators was 0.63 which is below the
      suggested ANSI threshold of 0.70. There was no statistically significant
      difference in results when stratified by respirator model. QNFT and QLFT produced
      different fit-test outcomes for the three respirator models examined. The
      disagreement in outcomes between the two fit-test methods with our suite of N95
      filtering facepiece respirators was approximately 12%. Our findings may benefit
      other healthcare organizations that use these three respirators.

PMID- 27717301
TI  - Respirable dust and silica exposure among World Trade Center cleanup workers.
AB  - The cleanup effort following the destruction of the World Trade Center (WTC) was
      unprecedented and involved removal of 1.8 million tons of rubble over a nine
      month period. Work at the site occurred 24 hr a day, 7 days a week and involved
      thousands of workers during the process. The Occupational Safety and Health
      Administration (OSHA) conducted personal and area exposure sampling during the
      cleanup of the site. Secondary data analysis was performed on OSHA air sampling
      data for respirable dust and silica from September 2001 to June 2002 at the WTC
      recovery site to characterize workers' exposure. Results for silica and
      respirable particulate were stratified by area and personal samples as well as
      job task for analysis. Of 1108 samples included in the analysis, 693 were
      personal and 415 were area. The mean result for personal silica samples was 42
      MUg/m3 (Range: 4.2-1800 MUg/m3). Workers identified as drillers had the highest
      mean silica exposure (72 MUg/m3; range: 5.8-800 MUg/m3) followed by workers
      identified as dock builders (67 MUg/m3; range: 5.8-670 MUg/m3). The mean result
      for personal samples for respirable particulate was 0.44 mg/m3 (range: 0.00010-13
      mg/m3). There were no discernable trends in personal respirable dust and silica
      concentrations with date.

PMID- 27717298
TI  - Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy.
AB  - BACKGROUND: On the basis of data from a phase 2 trial that compared the
      checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram
      of body weight in patients with advanced melanoma, this phase 3 trial evaluated
      ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete
      resection of stage III melanoma. METHODS: After patients had undergone complete
      resection of stage III cutaneous melanoma, we randomly assigned them to receive
      ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every
      3 weeks for four doses, then every 3 months for up to 3 years or until disease
      recurrence or an unacceptable level of toxic effects occurred. Recurrence-free
      survival was the primary end point. Secondary end points included overall
      survival, distant metastasis-free survival, and safety. RESULTS: At a median
      follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in
      the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio
      for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89;
      P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab
      group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72;
      95.1% CI, 0.58 to 0.88; P=0.001). The rate of distant metastasis-free survival at
      5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo
      group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to
      0.92; P=0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients
      in the ipilimumab group and in 26.2% of those in the placebo group. Immune
      related adverse events of grade 3 or 4 occurred in 41.6% of the patients in the
      ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab
      group, 5 patients (1.1%) died owing to immune-related adverse events.
      CONCLUSIONS: As adjuvant therapy for high-risk stage III melanoma, ipilimumab at
      a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence
      free survival, overall survival, and distant metastasis-free survival than
      placebo. There were more immune-related adverse events with ipilimumab than with
      placebo. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00636168
      , and EudraCT number, 2007-001974-10 .).

PMID- 27717299
TI  - Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer.
AB  - BACKGROUND: Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose)
      polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with
      ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as
      maintenance treatment for patients with platinum-sensitive, recurrent ovarian
      cancer. METHODS: In this randomized, double-blind, phase 3 trial, patients were
      categorized according to the presence or absence of a germline BRCA mutation
      (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were
      randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once
      daily. The primary end point was progression-free survival. RESULTS: Of 553
      enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib
      and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234
      assigned to niraparib and 116 to placebo). Patients in the niraparib group had a
      significantly longer median duration of progression-free survival than did those
      in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard
      ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9
      months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with
      homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to
      0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard
      ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most
      common grade 3 or 4 adverse events that were reported in the niraparib group were
      thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which
      were managed with dose modifications. CONCLUSIONS: Among patients with platinum
      sensitive, recurrent ovarian cancer, the median duration of progression-free
      survival was significantly longer among those receiving niraparib than among
      those receiving placebo, regardless of the presence or absence of gBRCA mutations
      or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro;
      ClinicalTrials.gov number, NCT01847274 .).

PMID- 27717302
TI  - MiR-20b Displays Tumor-Suppressor Functions in Papillary Thyroid Carcinoma by
      Regulating the MAPK/ERK Signaling Pathway.
AB  - BACKGROUND: MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs that play
      important roles in multiple biological processes. MiR-20b has been reported to be
      dysregulated in papillary thyroid carcinoma (PTC). However, the functional roles
      are still largely unknown. This study aimed to investigate the biological
      functions and the underlying molecular mechanisms of miR-20b in PTC. METHOD: The
      expression of miR-20b was assessed by quantitative reverse transcription
      polymerase chain reaction in 47 pairs of PTC and adjacent normal thyroid tissues.
      The association between miR-20b expression and clinicopathologic status of PTC
      patients was analyzed. MiR-20b was overexpressed in the PTC cell lines K1 and TPC
      1, and the effects on cell viability, migration, and invasion were evaluated. The
      study further searched for targets of miR-20b, and identified the possible
      molecular mechanisms of miR-20b in PTC cells. Additionally, the effect of miR-20b
      on tumor growth in nude mice was assessed. RESULTS: It was found that miR-20b was
      markedly downregulated in PTC tissues compared with their adjacent normal thyroid
      tissues. The low-level expression of miR-20b was correlated with cervical lymph
      node metastasis and TNM staging. Upregulation of miR-20b inhibited cell
      viability, migration, and invasion in K1 and TPC-1 cells. Ectopic overexpression
      of miR-20b could suppress the mitogen-activated protein kinase/extracellular
      signal-regulated kinase (MAPK/ERK) signaling pathway through directly targeting
      son of sevenless homolog 1 (SOS1) and extracellular signal-regulated kinase 2
      (ERK2). Furthermore, depletion of SOS1 or ERK2 by siRNAs has similar effects as
      miR-20b overexpression on cell viability and invasion, whereas rescued SOS1 or
      ERK2 expression partially reversed the inhibitory effects of miR-20b in TPC cell
      lines. In xenograft animal experiments, it was found that overexpressed miR-20b
      could suppress tumor growth of PTC cells. CONCLUSION: These results indicate for
      the first time that miR-20b displays tumor-suppressor functions in PTC. By
      targeting SOS1 and ERK2, miR-20b inhibits the activity of the MAPK/ERK signaling
      pathway. The findings suggest that miR-20b may play an important role in PTC
      initiation, progression, and metastasis, and may provide a potential therapeutic
      target for PTC.

PMID- 27717304
TI  - Je, a versatile suite to handle multiplexed NGS libraries with unique molecular
      identifiers.
AB  - BACKGROUND: The yield obtained from next generation sequencers has increased
      almost exponentially in recent years, making sample multiplexing common practice.
      While barcodes (known sequences of fixed length) primarily encode the sample
      identity of sequenced DNA fragments, barcodes made of random sequences (Unique
      Molecular Identifier or UMIs) are often used to distinguish between PCR
      duplicates and transcript abundance in, for example, single-cell RNA sequencing
      (scRNA-seq). In paired-end sequencing, different barcodes can be inserted at each
      fragment end to either increase the number of multiplexed samples in the library
      or to use one of the barcodes as UMI. Alternatively, UMIs can be combined with
      the sample barcodes into composite barcodes, or with standard Illumina(r)
      indexing. Subsequent analysis must take read duplicates and sample identity into
      account, by identifying UMIs. RESULTS: Existing tools do not support these
      complex barcoding configurations and custom code development is frequently
      required. Here, we present Je, a suite of tools that accommodates complex
      barcoding strategies, extracts UMIs and filters read duplicates taking UMIs into
      account. Using Je on publicly available scRNA-seq and iCLIP data containing UMIs,
      the number of unique reads increased by up to 36 %, compared to when UMIs are
      ignored. CONCLUSIONS: Je is implemented in JAVA and uses the Picard API. Code,
      executables and documentation are freely available at http://gbcs.embl.de/Je . Je
      can also be easily installed in Galaxy through the Galaxy toolshed.

PMID- 27717303
TI  - Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.
AB  - BACKGROUND: The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could
      potentially overcome or delay resistance to endocrine therapy in advanced breast
      cancer that is positive for hormone receptor (HR) and negative for human
      epidermal growth factor receptor 2 (HER2). METHODS: In this randomized, placebo
      controlled, phase 3 trial, we evaluated the efficacy and safety of the selective
      CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in
      668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic
      breast cancer who had not received previous systemic therapy for advanced
      disease. We randomly assigned the patients to receive either ribociclib (600 mg
      per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or
      placebo plus letrozole. The primary end point was investigator-assessed
      progression-free survival. Secondary end points included overall survival,
      overall response rate, and safety. A preplanned interim analysis was performed on
      January 29, 2016, after 243 patients had disease progression or died.
      Prespecified criteria for superiority required a hazard ratio of 0.56 or less
      with P<1.29*10-5. RESULTS: The duration of progression-free survival was
      significantly longer in the ribociclib group than in the placebo group (hazard
      ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29*10-6 for superiority). The median
      duration of follow-up was 15.3 months. After 18 months, the progression-free
      survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the
      ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In
      patients with measurable disease at baseline, the overall response rate was 52.7%
      and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were
      reported in more than 10% of the patients in either group were neutropenia (59.3%
      in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs.
      0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%,
      respectively. CONCLUSIONS: Among patients receiving initial systemic treatment
      for HR-positive, HER2-negative advanced breast cancer, the duration of
      progression-free survival was significantly longer among those receiving
      ribociclib plus letrozole than among those receiving placebo plus letrozole, with
      a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis
      Pharmaceuticals; ClinicalTrials.gov number, NCT01958021 .).

PMID- 27717305
TI  - A novel method for quantifying the rate of embryogenesis uncovers considerable
      genetic variation for the duration of embryonic development in Drosophila
      melanogaster.
AB  - BACKGROUND: Embryogenesis is a highly conserved, canalized process, and variation
      in the duration of embryogenesis (DOE), i.e., time from egg lay to hatching, has
      a potentially profound effect on the outcome of within- and between-species
      competition. There is both intra- and inter-specific variation in this trait,
      which may provide important fuel for evolutionary processes, particularly
      adaptation. However, while genetic variation underlying simpler morphological
      traits, or with large phenotypic effects is well described in the literature,
      less is known about the underlying genetics of traits, such as DOE, partly due to
      a lack of tools with which to study them. RESULTS: Here, we establish a novel
      microscope-based assay to survey genetic variation for the duration of
      embryogenesis (DOE). First, to establish the potential importance of DOE in
      competitive fitness, we performed a set of experiments where we experimentally
      manipulated the time until hatching, and show that short hatching times result in
      priority effect in the form of improved larval competitive ability. We then use
      our assay to measure DOE for 43 strains from the Drosophila Genetic Reference
      Panel (DGRP). Our assay greatly simplifies the measurement of DOE, making it
      possible to precisely quantify this trait for 59,295 individual embryos (mean +/-
      S.D. of 1103 +/- 293 per DGRP strain, and 1002 +/- 203 per control). We find
      extensive genetic variation in DOE, with a 15 % difference in rate between the
      slowest and fastest strains measured, and 89 % of phenotypic variation due to
      DGRP strain. Using sequence information from the DGRP, we perform a genome-wide
      association study, which suggests that some well-known developmental genes affect
      the speed of embryonic development. CONCLUSIONS: We showed that the duration of
      embryogenesis (DOE) can be efficiently and precisely measured in Drosophila, and
      that the DGRP strains show remarkable variation in DOE. A genome-wide analysis
      suggests that some well-known developmental genes are potentially associated with
      DOE. Further functional assays, or transcriptomic analysis of embryos from the
      DGRP, can validate the role of our candidates in early developmental processes.

PMID- 27717306
TI  - Close ecological relationship among species facilitated horizontal transfer of
      retrotransposons.
AB  - BACKGROUND: Horizontal transfer (HT) of genetic materials is increasingly being
      found in both animals and plants and mainly concerns transposable elements (TEs).
      Many crustaceans have big genome sizes and are thus likely to harbor high TE
      contents. Their habitat might offer them ample opportunities to exchange genetic
      materials with organisms that are ecologically close but taxonomically distant to
      them. RESULTS: In this study, we analyzed the transcriptome of Pacific white
      shrimp (Litopenaeus vannamei), an important economic crustacean, to explore
      traces of HT events. From a collection of newly assembled transcripts, we
      identified 395 high reliable TE transcripts, most of which were retrotransposon
      transcripts. One hundred fifty-seven of those transcripts showed highest
      similarity to sequences from non-arthropod organisms, including ray-finned
      fishes, mollusks and putative parasites. In total, 16 already known L. vannamei
      TE families are likely to be involved in horizontal transfer events. Phylogenetic
      analyses of 10 L. vannamei TE families and their homologues (protein sequences)
      revealed that L. vannamei TE families were generally more close to sequences from
      aquatic species. Furthermore, TEs from other aquatic species also tend to group
      together, although they are often distantly related in taxonomy. Sequences from
      parasites and microorganisms were also widely present, indicating their possible
      important roles in HT events. Expression profile analyses of transcripts in two
      NCBI BioProjects revealed that transcripts involved in HT events are likely to
      play important roles in antiviral immunity. More specifically, those transcripts
      might act as inhibitors of antiviral immunity. CONCLUSIONS: Close ecological
      relationship, especially predation, might greatly facilitate HT events among
      aquatic species. This could be achieved through exchange of parasites and
      microorganisms, or through direct DNA flow. The occurrence of HT events may be
      largely incidental, but the effects could be beneficial for recipients.

PMID- 27717307
TI  - Why do different oceanic archipelagos harbour contrasting levels of species
      diversity? The macaronesian endemic genus Pericallis (Asteraceae) provides
      insight into explaining the 'Azores diversity Enigma'.
AB  - BACKGROUND: Oceanic archipelagos typically harbour extensive radiations of
      flowering plants and a high proportion of endemics, many of which are restricted
      to a single island (Single Island Endemics; SIEs). The Azores represents an
      anomaly as overall levels of endemism are low; there are few SIEs and few
      documented cases of intra-archipelago radiations. The distinctiveness of the
      flora was first recognized by Darwin and has been referred to as the 'Azores
      Diversity Enigma' (ADE). Diversity patterns in the Macaronesian endemic genus
      Pericallis (Asteraceae) exemplify the ADE. In this study we used morphometric,
      Amplified Length Polymorphisms, and bioclimatic data for herbaceous Pericallis
      lineages endemic to the Azores and the Canaries, to test two key hypotheses
      proposed to explain the ADE: i) that it is a taxonomic artefact or Linnean
      shortfall, ie. the under description of taxa in the Azores or the over-splitting
      of taxa in the Canaries and (ii) that it reflects the greater ecological
      homogeneity of the Azores, which results in limited opportunity for ecological
      diversification compared to the Canaries. RESULTS: In both the Azores and the
      Canaries, morphological patterns were generally consistent with current taxonomic
      classifications. However, the AFLP data showed no genetic differentiation between
      the two currently recognized Azorean subspecies that are ecologically
      differentiated. Instead, genetic diversity in the Azores was structured
      geographically across the archipelago. In contrast, in the Canaries genetic
      differentiation was mostly consistent with morphology and current taxonomic
      treatments. Both Azorean and Canarian lineages exhibited ecological
      differentiation between currently recognized taxa. CONCLUSIONS: Neither a Linnean
      shortfall nor the perceived ecological homogeneity of the Azores fully explained
      the ADE-like pattern observed in Pericallis. Whilst variation in genetic data and
      morphological data in the Canaries were largely congruent, this was not the case
      in the Azores, where genetic patterns reflected inter-island geographical
      isolation, and morphology reflected intra-island bioclimatic variation. The
      combined effects of differences in (i) the extent of geographical isolation, (ii)
      population sizes and (iii) geographical occupancy of bioclimatic niche space,
      coupled with the morphological plasticity of Pericallis, may all have contributed
      to generating the contrasting patterns observed in the archipelagos.

PMID- 27717308
TI  - The effect of dietary restriction on reproduction: a meta-analytic perspective.
AB  - BACKGROUND: Dietary restriction (DR), a reduction in the amount of food or
      particular nutrients eaten, is the most consistent environmental manipulation to
      extend lifespan and protect against age related diseases. Current evolutionary
      theory explains this effect as a shift in the resolution of the trade-off between
      lifespan and reproduction. However, recent studies have questioned the role of
      reproduction in mediating the effect of DR on longevity and no study has
      quantitatively investigated the effect of DR on reproduction across species.
      RESULTS: Here we report a comprehensive comparative meta-analysis of the effect
      of DR on reproduction. In general, DR reduced reproduction across taxa, but
      several factors moderated this effect. The effect of DR on reproduction was
      greater in well-studied model species (yeast, nematode worms, fruit flies and
      rodents) than non-model species. This mirrors recent results for longevity and,
      for reproduction, seems to result from a faster rate of decline with decreasing
      resources in model species. Our results also suggested that not all reproductive
      traits are affected equally by DR. High and moderate cost reproductive traits
      suffered a significant reduction with DR, but low cost traits, such as ejaculate
      production, did not. Although the effect of DR on reproduction was stronger in
      females than males, this sex difference reduced to near zero when accounting for
      other co-factors such as the costliness of the reproductive trait. Thus, sex
      differences in the effect of DR on longevity may be due to a failure to expose
      males to as complete a range of the costs of reproduction as females.
      CONCLUSIONS: We suggest that to better understand the generality of the effect of
      DR, future studies should attempt to address the cause of the apparent model
      species bias and ensure that individuals are exposed to as many of the costs of
      reproduction as possible. Furthermore, our meta-analytic approach reveals a
      general shortage of DR studies that record reproduction, particularly in males,
      as well as a lack of direct side-by-side comparisons of the effect of DR on males
      and females.

PMID- 27717309
TI  - RStrucFam: a web server to associate structure and cognate RNA for RNA-binding
      proteins from sequence information.
AB  - BACKGROUND: RNA-binding proteins (RBPs) interact with their cognate RNA(s) to
      form large biomolecular assemblies. They are versatile in their functionality and
      are involved in a myriad of processes inside the cell. RBPs with similar
      structural features and common biological functions are grouped together into
      families and superfamilies. It will be useful to obtain an early understanding
      and association of RNA-binding property of sequences of gene products. Here, we
      report a web server, RStrucFam, to predict the structure, type of cognate RNA(s)
      and function(s) of proteins, where possible, from mere sequence information.
      RESULTS: The web server employs Hidden Markov Model scan (hmmscan) to enable
      association to a back-end database of structural and sequence families. The
      database (HMMRBP) comprises of 437 HMMs of RBP families of known structure that
      have been generated using structure-based sequence alignments and 746 sequence
      centric RBP family HMMs. The input protein sequence is associated with structural
      or sequence domain families, if structure or sequence signatures exist. In case
      of association of the protein with a family of known structures, output features
      like, multiple structure-based sequence alignment (MSSA) of the query with all
      others members of that family is provided. Further, cognate RNA partner(s) for
      that protein, Gene Ontology (GO) annotations, if any and a homology model of the
      protein can be obtained. The users can also browse through the database for
      details pertaining to each family, protein or RNA and their related information
      based on keyword search or RNA motif search. CONCLUSIONS: RStrucFam is a web
      server that exploits structurally conserved features of RBPs, derived from known
      family members and imprinted in mathematical profiles, to predict putative RBPs
      from sequence information. Proteins that fail to associate with such structure
      centric families are further queried against the sequence-centric RBP family HMMs
      in the HMMRBP database. Further, all other essential information pertaining to an
      RBP, like overall function annotations, are provided. The web server can be
      accessed at the following link: http://caps.ncbs.res.in/rstrucfam .

PMID- 27717310
TI  - Faecal calprotectin: factors affecting levels and its potential role as a
      surrogate marker for risk of development of Crohn's Disease.
AB  - BACKGROUND: Faecal calprotectin (FC) is one of the most widely used non-invasive
      tests for the diagnosis and assessment of Crohn's disease (CD) activity. Despite
      this, factors other than disease activity which affect levels have not been
      extensively reviewed. This is of importance when using FC in the diagnostic
      setting but also may be of utility in studying the aetiology of disease.
      OBJECTIVES: Our review outlines environmental risk factors that affect FC levels
      influencing diagnostic accuracy and how these may be associated with risk of
      developing CD. FC as a surrogate marker could be used to validate risk factors
      established in case control studies where prospective studies are not feasible.
      Proof of this concept is provided by our identification of obesity as being
      associated with elevated FC, our subsequent confirmation of obesity as risk
      factor for CD and the subsequent verification in prospective studies, as well as
      associations of lack of physical activity and dietary fibre intake with elevated
      FC levels and their subsequent confirmation as risk factors in prospective
      studies. CONCLUSION: We believe that FC is likely to prove a useful surrogate
      marker for risk of developing CD. This review has given a theoretical basis for
      considering the epidemiological determinants of CD which to date has been
      missing.

PMID- 27717311
TI  - Formation of diploid and triploid hybrid groupers (hybridization of Epinephelus
      coioides ? * Epinephelus lanceolatus ?) and their 5S gene analysis.
AB  - BACKGROUND: Interspecies hybridization is widely used to achieve heterosis or
      hybrid vigor, which has been observed and harnessed by breeders for centuries.
      Natural allopolyploid hybrids generally exhibit more superior heterosis than both
      the diploid progenies and their parental species. However, polyploid formation
      processes have been long ignored, the genetic basis of heterosis in polyploids
      remains elusive. RESULTS: In the present study, triploid hybrids had been
      demonstrated to contain two sets of chromosomes from mother species and one set
      from father species. Cellular polyploidization process in the embryos had been
      traced. The triploid hybrids might be formed by failure formation of the second
      polarized genome during the second meiosis stage. Four spindle centers were
      observed in anaphase stage of the first cell division. Three spindle centers were
      observed in side of cell plate after the first cell division. The 5S rDNA genes
      of four types of groupers were cloned and analyzed. The diploid and triploid
      hybrids had been proved to contain the tandem chimera structures which were
      recombined by maternal and paternal monomer units. The results indicated that
      genome re-fusion had occurred in the hybrid progenies. To further elucidate the
      genetic patterns of diploid and triploid hybrids, fluorescence chromosome
      location had been carried out, maternal 5S gene (M-386) were used as the probe.
      The triploid hybrids contained fewer fluorescence loci numbers than the maternal
      species. The results indicated that participation of paternal 5S gene in the
      triploid hybrid genome had degraded the match rates of M-386 probe. CONCLUSIONS:
      Our study is the first to investigate the cellular formation processes of natural
      allopolyploids in hybrid fish, the cellular polyploidization process may be
      caused by failure formation of the second polarized genome during the meiosis,
      and our results will provide the molecular basis of hybrid vigor in interspecies
      hybridization.

PMID- 27717313
TI  - Heterozygous p.S811F RET gene mutation associated with renal agenesis,
      oligomeganephronia and total colonic aganglionosis: a case report.
AB  - BACKGROUND: Several shared common gene networks participate in development of
      interstinal ganglia and also nephron formation; the glial cell line-derived
      neurotrophic factor/Ret/glial cell line-derived neurotrophic factor receptor gene
      network is particularly important. CASE PRESENTATION: We encountered a patient
      with total colonic aganglionosis as well as right renal agenesis and
      oligomeganephronia. Gene analysis in this patient disclosed a heterozygous
      p.S811F mutation was in Ret gene exon 14, resulting in a substitution of
      phenylalanine for serine. The large side chain of phenylalanine obstructed the
      opening of the hydrophobic pocket of the Ret molecule causing interference with
      its interaction with adenosine triphosphate and consequent marked reduction in
      its enzyme activity. This could account for our patient's severe intestinal
      disease and renal dysplasia. We know of no previous reports of concomitant
      Hirschsprung's disease and oligomeganephronia. CONCLUSIONS: The patient's overall
      illness could be considered a novel Ret gene mutation syndrome.

PMID- 27717312
TI  - Members of WRKY Group III transcription factors are important in TYLCV defense
      signaling pathway in tomato (Solanum lycopersicum).
AB  - BACKGROUND: Transmitted by the whitefly Bemisia tabaci, tomato yellow leaf curly
      virus (TYLCV) has posed serious threats to plant growth and development. Plant
      innate immune systems against various threats involve WRKY Group III
      transcription factors (TFs). This group participates as a major component of
      biological processes in plants. RESULTS: In this study, 6 WRKY Group III TFs
      (SolyWRKY41, SolyWRKY42, SolyWRKY53, SolyWRKY54, SolyWRKY80, and SolyWRKY81) were
      identified, and these TFs responded to TYLCV infection. Subcellular localization
      analysis indicated that SolyWRKY41 and SolyWRKY54 were nuclear proteins in vivo.
      Many elements, including W-box, were found in the promoter region of Group III
      TFs. Interaction network analysis revealed that Group III TFs could interact with
      other proteins, such as mitogen-activated protein kinase 5 (MAPK) and
      isochorismate synthase (ICS), to respond to biotic and abiotic stresses. Positive
      and negative expression patterns showed that WRKY Group III genes could also
      respond to TYLCV infection in tomato. The DNA content of TYLCV resistant lines
      after SolyWRKY41 and SolyWRKY54 were subjected to virus-induced gene silencing
      (VIGS) was lower than that of the control lines. CONCLUSIONS: In the present
      study, 6 WRKY Group III TFs in tomato were identified to respond to TYLCV
      infection. Quantitative real-time-polymerase chain reaction (RT-qPCR) and VIGS
      analyses demonstrated that Group III genes served as positive and negative
      regulators in tomato-TYLCV interaction. WRKY Group III TFs could interact with
      other proteins by binding to cis elements existing in the promoter regions of
      other genes to regulate pathogen-related gene expression.

PMID- 27717314
TI  - High frequency of pre-existing neutralizing antibody responses in patients with
      dengue during an outbreak in Central Brazil.
AB  - BACKGROUND: This study aims to identify dengue neutralizing antibody response in
      patients with dengue from a well-characterized cohort during an outbreak in
      central Brazil, 2012-2013. METHODS: We analyzed paired samples from 40 patients
      with severe dengue and 20 patients with dengue. Eligibility criteria were: IgM,
      NS1Ag and/or RT-PCR positivity and positive IgG result. Plaque reduction
      neutralization test (PRNT50) from DENV-1 to DENV-4 was performed to identify
      serotype-specific NAbs response. An infecting serotype was defined as >=4-fold
      increase in DENV NAbs in paired samples. Monotypic response was classified as
      PRNT50 >= 1/20 to only one DENV serotype, and multitypic response was considered
      to be PRNT50 >= 1/20 to two or more serotypes simultaneously. RESULTS: Patients
      were mainly adults. Virological dengue infection was confirmed by RT-PCR: DENV
      4(n = 14) and DENV-1(n = 10). Forty-four out of 60(73.3 %) patients had NAbs to
      DENV-4, DENV-1(68.3 %), DENV-2(68.3 %) and DENV-3(61.6 %) respectively. Fifteen
      percent of the cases presented monotypic response, whereas 85 % had multitypic
      response. DENV-4 infected-patients presented the greatest difference in PRNT50
      titers compared with other serotypes. Pre-existing DENV NAbs was not correlated
      with disease severity. This was the first time that DENV-4 was implicated in an
      epidemic in the region. CONCLUSION: Our data indicates high exposure of multiple
      DENV serotypes in all age groups in the pre-dengue vaccine era and also previous
      to Zika virus introduction in Brazil.

PMID- 27717315
TI  - A phase I study of nedaplatin, pemetrexed and thoracic intensity-modulated
      radiotherapy for inoperable stage III lung adenocarcinoma.
AB  - BACKGROUND: Concurrent chemotherapy and radiation is the standard treatment for
      unresectable stage III Lung adenocarcinoma. However, no optimal concurrent
      chemotherapeutic regimen has been described. This study aimed to assess
      concurrent pemetrexed, nedaplatin and thoracic intensity-modulated radiotherapy
      followed by consolidation pemetrexed/nedaplatin for unresectable Stage IIIA/B
      lung adenocarcinoma. METHODS: Patients with unresectable stage III lung
      adenocarcinoma received thoracic intensity-modulated radiotherapy at 60-64 Gy in
      30-32 fractions, concurrently with two cycles of 500 mg/m2 pemetrexed, with
      nedaplatin doses escalating from 60 mg/m2 (level 1) to 70 mg/m2 (level 2) and 80
      mg/m2 (level 3). Consolidation consisted of three pemetrexed/nedaplatin (500
      mg/m2, 60 mg/m2) cycles every 3 weeks after concurrent therapy. The primary
      objective of the safety was to determine the maximum-tolerated dose (MTD). The
      secondary endpoints included response rate, PFS and OS. RESULTS: Fifteen patients
      were enrolled, including 3, 6 and 6 individuals in the first, second, and third
      dose levels, respectively. Three cases of dose-limiting toxicities (grade 3
      hepatitis, pneumonitis, and grade 4 thrombocytopenia), including one and two
      patients at levels 2 and 3, respectively, were observed and resulted in
      discontinued/delayed treatment. Response rates were 86.7 % (95 % confidence
      interval [CI], 64.2-97.8 %) and 64.3 % (95 % CI, 38.3-85.4 %) at chemoradiation
      and treatment completions, respectively. Median OS was 30.0 months (95 % CI, 16.4
      43.6 months); 2-year OS was 44.0 % (95 % CI, 18.7-69.2 %). Median PFS was 12.0
      months (95 % CI, 6.9-17.0 months), and the 2-year PFS 27.0 % (95 % CI, 4.7-49.3
      %). CONCLUSIONS: Full dose 500 mg/m2 of pemetrexed and nedaplatin 70 mg/m2 could
      be used safely with thoracic intensity-modulated radiotherapy for inoperable
      stage III lung adenocarcinoma. Further evaluation of stage III lung
      adenocarcinoma management is warranted. TRIAL REGISTRATION: This study was
      retrospectively registered at Chinese Clinical Trial Registry ( ChiCTR-OPN
      16008316 , April 2016).

PMID- 27717316
TI  - A rare c.183_187dupCTCAC mutation of the acetylcholine receptor CHRNE gene in a
      South Asian female with congenital myasthenic syndrome: a case report.
AB  - BACKGROUND: Congenital myasthenic syndromes (CMSs) occur as a result of genetic
      mutations that cause aberrations in structure and/or function of proteins
      involved in neuromuscular transmission. Acetylcholine receptor epsilon (epsilon)
      subunit (CHRNE) gene mutations account for about 30-50 % of genetically diagnosed
      cases. We report a rare CHRNE gene mutation in a South Asian female with CMS.
      CASE PRESENTATION: A 17-year-old Maldivian female presented with bilateral
      partial ptosis, fatigable proximal muscle weakness and slurring of speech noted
      since the age of 2 years. She could not run, had difficulty negotiating stairs
      and rising from a seated position, and fatigues when speaking at length. Her
      birth and past medical histories were otherwise unremarkable. There is no
      parental consanguinity or family history of muscle disorders. On examination, she
      had a BMI of 18 kg/m2, bilateral fatigable partial ptosis, complete external
      ophthalmoplegia and fatigable proximal muscle weakness (MRC grade 4/5). Apart
      from spinal scoliosis the rest of the examination was normal. Haematological and
      biochemical investigations including serum lactate level and thyroid functions
      were normal. Acetylcholine receptor antibodies and muscle specific kinase
      antibodies were not detected in serum. Repetitive nerve stimulation showed marked
      decrement (>30 %) in nerve-muscle pairs in the face and forearm. Her DNA
      sequencing revealed a c.183-187dupCTCAC mutation in CHRNE. She remained
      functionally independent on pyridostigmine treatment. CONCLUSIONS: This case
      describes a rare mutation of the CHRNE gene in CMS and highlights the relevance
      of genetic diagnosis in CMS. It further adds to map the occurrence of such
      mutations in Asian populations.

PMID- 27717317
TI  - The feasibility and diagnostic accuracy by multiple cardiac biomarkers in
      emergency chest pain patients: a clinical analysis to compare 290 suspected acute
      coronary syndrome cases stratified by age and gender in Taiwan.
AB  - BACKGROUND: Accurate diagnosis of acute coronary syndrome (ACS) in a timely
      fashion is challenging in the elderly population, especially elderly women, who
      usually exhibit atypical clinical symptoms. A multiple cardiac biomarker (MCB)
      based approach has been shown to improve diagnostic efficacy of ACS. However,
      data in various age groups and sex differences remain largely unexplored.
      METHODS: Point-of-care testing (POCT) was performed on 290 patients (aged >=18
      years) who were admitted to the emergency department (ED) with symptoms of acute
      chest pain under suspicion of acute coronary syndrome (ACS). The MCB approach in
      current work assessed four cardiac biomarkers: myoglobin, troponin I, creatine
      kinase-myocardial band isoenzyme fraction (CK-MB), and brain natriuretic peptide
      (BNP). RESULTS: Overall, the MCB approach demonstrated considerably higher
      sensitivity for elderly patients than for younger patients in identifying ACS
      (80.0 % [64.1-90.0] vs. 52.6 % [37.3-67.5] for >=65 years and <65 years groups),
      with younger population showed greater specificity (44.1 % [35.3-53.4] vs. 84.9 %
      [76.9-90.5] for >=65 years and <65 years groups, respectively). The highest
      sensitivity achieved for elderly women who reported chest pain was 87.5 % [95 %
      CI: 64-96.5]). In general, the sensitivity of this approach was higher for female
      patients than for male patients (80 % [58.4-91.9] vs. 61 % [47.8-73.0]).
      CONCLUSIONS: The MCB approach can provide a quick and accurate clinical diagnosis
      in elderly and female patients, both of whom have traditionally proven to be
      challenging to diagnose from suspected acute coronary syndrome.

PMID- 27717318
TI  - Recombinant domains III of Tick-Borne Encephalitis Virus envelope protein in
      combination with dextran and CpGs induce immune response and partial
      protectiveness against TBE virus infection in mice.
AB  - BACKGROUND: E protein of tick-borne encephalitis virus (TBEV) and other
      flaviviruses is located on the surface of the viral particle. Domain III of this
      protein seems to be a promising component of subunit vaccines for prophylaxis of
      TBE and kits for diagnostics of TBEV. METHODS: Three variants of recombinant TBEV
      E protein domain III of European, Siberian and Far Eastern subtypes fused with
      dextran-binding domain of Leuconostoc citreum KM20 were expressed in E. coli and
      purified. The native structure of domain III was confirmed by ELISA antibody kit
      and sera of patients with tick-borne encephalitis. Immunogenic and protective
      properties of the preparation comprising these recombinant proteins immobilized
      on a dextran carrier with CpG oligonucleotides as an adjuvant were investigated
      on the mice model. RESULTS: All 3 variants of recombinant proteins immobilized on
      dextran demonstrate specific interaction with antibodies from the sera of TBE
      patients. Thus, constructed recombinant proteins seem to be promising for TBE
      diagnostics. The formulation comprising the 3 variants of recombinant antigens
      immobilized on dextran and CpG oligonucleotides, induces the production of
      neutralizing antibodies against TBEV of different subtypes and demonstrates
      partial protectivity against TBEV infection. CONCLUSIONS: Studied proteins
      interact with the sera of TBE patients, and, in combination with dextran and
      CPGs, demonstrate immunogenicity and limited protectivity on mice compared with
      reference "Tick-E-Vac" vaccine.

PMID- 27717319
TI  - Does acupuncture have a role in the treatment of threatened miscarriage? Findings
      from a feasibility randomised trial and semi-structured participant interviews.
AB  - BACKGROUND: Threatened miscarriage is a common complication of early pregnancy
      increasing the risk of miscarriage or premature labour. Currently there is
      limited evidence to recommend any biomedical pharmacological or self-care
      management, resulting in a 'watchful waiting' approach. The objective of this
      study was to examine the feasibility of offering acupuncture as a therapeutic
      treatment for women presenting with threatened miscarriage. METHODS: A mixed
      methods study involving a randomised controlled trial and semi structured
      interviews. A pragmatic acupuncture protocol including medical self-care advice
      was compared to an active control receiving touch intervention and medical self
      care advice. Descriptive statistics were used to examine the demographic and
      baseline characteristics. Endpoints were analysed between groups using a mean t
      test and chi-square tests with P < 0.05 considered statistically significant.
      Dichotomous data was expressed as Risk Ratio with 95 % confidence intervals.
      Eleven participants were purposively interviewed about their experiences on
      exiting the trial with interviews analysed using thematic analysis. RESULTS:
      Forty women were successfully randomised. For women receiving acupuncture there
      was a statically significant reduction with threatened miscarriage symptoms
      including bleeding, cramping and back pain compared with the control (p = 0.04).
      Thematic analysis revealed women were dissatisfied with the medical support and
      advice received. An overarching theme emerged from the data of 'finding something
      you can do.' This encompassed the themes: 'they said there was nothing they could
      do,' 'feeling the benefits' and 'managing while marking time.' CONCLUSION:
      Acupuncture was a feasible intervention and reduced threatened miscarriage
      symptoms when compared to a touch intervention. Further research is required to
      further explore acupuncture use for this common complication and whether it can
      reduce the incidence of miscarriage. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry (ANZCTR), ACTRN12610000850077 . Date of registration
      12/10/2010. Retrospectively registered, with first participant enrolled
      11/10/2012.

PMID- 27717320
TI  - The relevance of nerve mobility on function and activity in children with
      Cerebral Palsy.
AB  - BACKGROUND: In children with cerebral palsy (CP), stiffness, caused by
      contractile and non-contractile structures, can influence motor performance. This
      study sought to determine whether the nerve mobility had a relevant impact on
      motor performance in children with CP. We hypothesized that a positive Straight
      Leg Raise (SLR) test, as well as smaller SLR hip angle, would relate to lower leg
      muscle strength, reduced motor capacity and less motor performance in children
      with CP. METHODS: We applied a cross-sectional analysis on data including SLR,
      leg muscle strength, Gross Motor Function Measure (GMFM-66) and number of
      activity counts during daily life from thirty children with CP (6-18 years). We
      performed receiver operating characteristics and correlation analyses. RESULTS:
      Positive SLR test could distinguish well between children with low versus high
      muscle strength and GMFM-66 scores. The SLR hip angle correlated significant with
      the level of disability and with muscle strength. The correlation with the GMFM
      66 and the activity counts was fair. CONCLUSION: This study suggests that neural
      restriction of SLR is higher on functional and activity outcome than the measured
      SLR hip range of motion. Further studies should investigate weather improving
      nerve mobility can lead to an amelioration of function in children with CP.

PMID- 27717321
TI  - Mechanisms and direction of allocation bias in randomised clinical trials.
AB  - BACKGROUND: Selective allocation of patients into the compared groups of a
      randomised trial may cause allocation bias, but the mechanisms behind the bias
      and its directionality are incompletely understood. We therefore analysed the
      mechanisms and directionality of allocation bias in randomised clinical trials.
      METHODS: Two systematic reviews and a theoretical analysis. We conducted one
      systematic review of empirical studies of motives/methods for deciphering patient
      allocation sequences; and another review of methods publications commenting on
      allocation bias. We theoretically analysed the mechanisms of allocation bias and
      hypothesised which main factors predicts its direction. RESULTS: Three empirical
      studies addressed motives/methods for deciphering allocation sequences. Main
      motives included ensuring best care for patients and ensuring best outcome for
      the trial. Main methods included various manipulations with randomisation
      envelopes. Out of 57 methods publications 11 (19 %) mentioned explicitly that
      allocation bias can go in either direction. We hypothesised that the direction of
      allocation bias is mainly decided by the interaction between the patient
      allocators' motives and treatment preference. CONCLUSION: Inadequate allocation
      concealment may exaggerate treatment effects in some trials while underestimate
      effects in others. Our hypothesis provides a theoretical overview of the main
      factors responsible for the direction of allocation bias.

PMID- 27717322
TI  - Ergocalciferol treatment does Not improve erythropoietin utilization and
      hospitalization rate in hemodialysis patients.
AB  - BACKGROUND: Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency (VDD) is highly
      prevalent in chronic kidney disease. The aim of this study was to evaluate the
      effect of oral ergocalciferol supplementation on requirement of erythropoietin
      (EPO) and active vitamin D analogues, and hospitalization rate in maintenance
      hemodialysis (HD) patients. METHODS: This retrospective cohort study included 186
      patients who were on HD for 3 months and had 25(OH)D levels < 30 ng/ml. Over 1
      year period, 107 patients were supplemented with protocol-based ergocalciferol
      (D2 group) and 79 were not (control). Parameters of erythropoiesis and bone
      mineral metabolism, and monthly doses of EPO and paricalcitol were assessed at 6-
      and 12- months of ergocalciferol supplementation. Total hospitalizations were
      recorded for the same year. RESULTS: Baseline characteristics were similar across
      two arms except higher serum ferritin, transferrin saturation and prevalence of
      stroke in D2 and higher coronary artery disease in control group with overall
      mean +/- SD 25(OH)D level of 16.8 +/- 7 ng/ml. At 12 months, 25(OH)D levels
      increased significantly in D2 group compared to control (30.5 +/- 11.7 vs. 14.2
      +/- 9.3 ng/ml; p < 0.001). The EPO dose remained same with no difference in
      hemoglobin values between the two groups during the intervention period. On
      multivariate regression which included above variables there was no effect of
      ergocalciferol treatment on EPO dose (p = ns). Hospitalization rate was similar
      in two arms; however, ergocalciferol treatment inversely associated with
      paricalcitol dose (beta +/- SE = -10.4 +/- 2.8; p < 0.001). CONCLUSIONS: One-year
      of ergocalciferol supplementation was not associated with reduction in EPO
      requirement or hospitalization rate in HD patients with VDD. Further studies are
      warranted to determine definitive role of nutritional vitamin D in these
      patients.

PMID- 27717323
TI  - Outcome of low dose cyclophosphamide for induction phase treatment of lupus
      nephritis, a single center study.
AB  - BACKGROUND: The current standard for induction phase treatment of lupus nephritis
      is steroid combined with mycophenolate mofetil or pulse intravenous
      cyclophosphamide (IVC). The lowest dose of IVC recommended for induction therapy
      is that used in the Euro-Lupus Trial. It is not known whether same cumulative
      dose of IVC would be effective when given over six months. METHODS: We carried
      out a prospective, observational study on 41 patients of biopsy-proven lupus
      nephritis (class III, IV, V or mixed). For induction, patients received six
      pulses of monthly IVC (500 mg each), along with steroid. Patients were followed
      up monthly until one month beyond completion of the sixth pulse. The outcomes
      assessed were complete remission (proteinuria < 200 mg/day or urine albumin nil
      with serum albumin >35 gm/L, stable estimated glomerular filtration rate (eGFR)
      if normal at baseline or increase in eGFR by 25 % if abnormal at baseline and
      normal urinary sediment), response (complete or partial remissions),
      complications of therapy and death. RESULTS: Twenty two patients (53.7 %) had
      class IV nephritis. Eighteen patients (43.9 %) achieved complete remission, 16
      (39.0 %) achieved partial remission, yielding an overall response rate of 82.9 %.
      Nephrotic range proteinuria (UTP >= 3 g/day) and severe hypoalbuminemia (serum
      albumin < 20 g/L) at baseline influenced remission (p <0.05). Infection, seen in
      12 patients (29.3 %), was the most common complication. Four deaths (9.6 %) were
      observed, all due to infection. CONCLUSIONS: For induction phase treatment,
      Nepalese patients with lupus nephritis responded favorably to steroid and low
      dose IVC of 3 grams given as six monthly pulses.

PMID- 27717324
TI  - The prevalence of stroke and depression and factors associated with depression in
      elderly people with and without stroke.
AB  - BACKGROUND: Few studies have investigated factors associated with depression
      among elderly people with and without stroke concurrently, using identical
      settings, procedures and study variables. The aim was to investigate the
      prevalence of stroke and depression and to compare the factors associated with
      depression in people with and without stroke. METHODS: A postal mail survey was
      sent to 65-, 70-, 75- and 80-year-olds in northern Sweden and Finland in 2010 (n
      = 6098). Stroke was defined as answering "yes" to the question "Have you had a
      stroke?" Depression was defined as answering "yes" to the question "Are you
      depressed?" or having a Geriatric Depression Scale-4 score >=2. Dependence in
      personal activities of daily living was defined as not showering without human
      assistance. Associations were tested with log-binomial regression. RESULTS: The
      overall stroke prevalence was 7.0 +/- 0.3 % and increased from 4.7 +/- 0.4 %
      among 65-year-olds to 11.6 +/- 1.0 % among 80-year-olds (p < 0.001). The overall
      depression prevalence was 12.8 +/- 0.4 % and increased from 11.0 +/- 0.6 % among
      65-year-olds to 18.1 +/- 1.2 % among 80-year-olds (p < 0.001). Depression was
      more common among people with stroke (Prevalence Ratio 1.77, 95 % Confidence
      Interval 1.48-2.12). In the non-stroke group, depression was independently
      associated with diabetes, dependence in instrumental activities of daily living,
      living alone, not having someone to talk to, poor finances, pain problems and
      having a life crisis in the preceding year. In the group with stroke, depression
      was independently associated with dependence in personal activities of daily
      living and having a life crisis the preceding year. CONCLUSIONS: Depression in
      people without stroke appeared to be independently associated with a broader
      range of external factors than depression in people with stroke.

PMID- 27717325
TI  - Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum.
AB  - BACKGROUND: Corynebacterium glutamicum is a well-studied bacterium which
      naturally overproduces glutamate when induced by an elicitor. Glutamate
      production is accompanied by decreased 2-oxoglutatate dehydrogenase activity.
      Elicitors of glutamate production by C. glutamicum analyzed to molecular detail
      target the cell envelope. RESULTS: Ciprofloxacin, an inhibitor of bacterial DNA
      gyrase and topoisomerase IV, was shown to inhibit growth of C. glutamicum wild
      type with concomitant excretion of glutamate. Enzyme assays showed that 2
      oxoglutarate dehydrogenase activity was decreased due to ciprofloxacin addition.
      Transcriptome analysis revealed that this inhibitor of DNA gyrase increased RNA
      levels of genes involved in DNA synthesis, repair and modification. Glutamate
      production triggered by ciprofloxacin led to glutamate titers of up to 37 +/- 1
      mM and a substrate specific glutamate yield of 0.13 g/g. Even in the absence of
      the putative glutamate exporter gene yggB, ciprofloxacin effectively triggered
      glutamate production. When C. glutamicum wild type was cultivated under nitrogen
      limiting conditions, 2-oxoglutarate rather than glutamate was produced as
      consequence of exposure to ciprofloxacin. Recombinant C. glutamicum strains
      overproducing lysine, arginine, ornithine, and putrescine, respectively, secreted
      glutamate instead of the desired amino acid when exposed to ciprofloxacin.
      CONCLUSIONS: Ciprofloxacin induced DNA synthesis and repair genes, reduced 2
      oxoglutarate dehydrogenase activity and elicited glutamate production by C.
      glutamicum. Production of 2-oxoglutarate could be triggered by ciprofloxacin
      under nitrogen-limiting conditions.

PMID- 27717326
TI  - Fall risk as a function of time after admission to sub-acute geriatric hospital
      units.
AB  - BACKGROUND: There is evidence about time-dependent fracture rates in different
      settings and situations. Lacking are data about underlying time-dependent fall
      risk patterns. The objective of the study was to analyse fall rates as a function
      of time after admission to sub-acute hospital units and to evaluate the time
      dependent impact of clinical factors at baseline on fall risk. METHODS: This
      retrospective cohort study used data of 5,255 patients admitted to sub-acute
      units in a geriatric rehabilitation clinic in Germany between 2010 and 2014.
      Falls, personal characteristics and functional status at admission were extracted
      from the hospital information system. The rehabilitation stay was divided in 3
      day time-intervals. The fall rate was calculated for each time-interval in all
      patients combined and in subgroups of patients. To analyse the influence of
      covariates on fall risk over time multivariate negative binomial regression
      models were applied for each of 5 time-intervals. RESULTS: The overall fall rate
      was 10.2 falls/1,000 person-days with highest fall risks during the first week
      and decreasing risks within the following weeks. A particularly pronounced risk
      pattern with high fall risks during the first days and decreasing risks
      thereafter was observed in men, disoriented people, and people with a low
      functional status or impaired cognition. In disoriented patients, for example,
      the fall rate decreased from 24.6 falls/1,000 person-days in day 2-4 to about 13
      falls/1,000 person-days 2 weeks later. The incidence rate ratio of baseline
      characteristics changed also over time. CONCLUSIONS: Fall risk differs
      considerably over time during sub-acute hospitalisation. The strongest
      association between time and fall risk was observed in functionally limited
      patients with high risks during the first days after admission and declining
      risks thereafter. This should be considered in the planning and application of
      fall prevention measures.

PMID- 27717327
TI  - Does conservation account for splicing patterns?
AB  - BACKGROUND: Alternative mRNA splicing is critical to proteomic diversity and
      tissue and species differentiation. Exclusion of cassette exons, also called exon
      skipping, is the most common type of alternative splicing in mammals. RESULTS: We
      present a computational model that predicts absolute (though not tissue
      differential) percent-spliced-in of cassette exons more accurately than previous
      models, despite not using any 'hand-crafted' biological features such as motif
      counts. We achieve nearly identical performance using only the conservation score
      (mammalian phastCons) of each splice junction normalized by average conservation
      over 100 bp of the corresponding flanking intron, demonstrating that conservation
      is an unexpectedly powerful indicator of alternative splicing patterns. Using
      this method, we provide evidence that intronic splicing regulation occurs
      predominantly within 100 bp of the alternative splice sites and that conserved
      elements in this region are, as expected, functioning as splicing regulators. We
      show that among conserved cassette exons, increased conservation of flanking
      introns is associated with reduced inclusion. We also propose a new definition of
      intronic splicing regulatory elements (ISREs) that is independent of
      conservation, and show that most ISREs do not match known binding sites or
      splicing factors despite being predictive of percent-spliced-in. CONCLUSIONS:
      These findings suggest that one mechanism for the evolutionary transition from
      constitutive to alternative splicing is the emergence of cis-acting splicing
      inhibitors. The association of our ISREs with differences in splicing suggests
      the existence of novel RNA-binding proteins and/or novel splicing roles for known
      RNA-binding proteins.

PMID- 27717329
TI  - QuantiFERON conversion following tuberculin administration is common in HIV
      infection and relates to baseline response.
AB  - BACKGROUND: HIV-1 infection impairs tuberculosis (TB) specific immune responses
      affecting the diagnosis of latent TB. We aimed to (1) determine the proportion of
      HIV-1-infected adults with a negative QuantiFERON(r)-TB Gold in-tube (QFT-GIT)
      and Tuberculin skin testing (TST) that convert to QFT-GIT positive following TST,
      and (2) evaluate the relationship between conversion and baseline QFT-GIT
      results. METHODS: HIV-1 infected adults being screened for a TB vaccine study in
      South Africa underwent QFT-GIT followed by TST. As per protocol, QFT-GIT was
      repeated if randomization was delayed allowing for evaluation of TST boosting in
      a proportion of participants. RESULTS: Of the 22 HIV-1 infected, TST and QFT-GIT
      negative adults (median CD4 477/mm3 IQR 439-621) who had QFT-GIT repeated after
      median 62 days (IQR 49-70), 40.9 % (95 % CI 18.6-63.2 %) converted. Converters
      had a significantly greater increase in the background subtracted TB antigen
      response (TBAg-Nil - all units IU/mL) following TST, 0.82 (IQR 0.39-1.28) vs 0.03
      (IQR -0.05-0.06), p = 0.0001. Those who converted also had a significantly higher
      baseline TBAg-Nil 0.21(IQR 0.17-0.26) vs 0.02(IQR 0.01-0.07), p = 0.002.
      Converters did not differ with regard to CD4 count or ART status. ROC analysis
      showed a baseline cut off of 0.15 correctly classified 86.4 % of converters with
      88.9 % sensitivity. CONCLUSIONS: Our findings support the possibility that there
      are 2 distinct groups in an HIV-1 infected population with negative QFT-GIT and
      TST; a true negative group and a group showing evidence of a weak Mtb specific
      immune response that boosts significantly following TST resulting in conversion
      of the test result that may represent false negatives. Further evaluation of
      whether a lower cut off may improve sensitivity of QFT-GIT in this population is
      warranted.

PMID- 27717328
TI  - Nationwide distribution of varicella-zoster virus clades in China.
AB  - BACKGROUND: In 2010, a universal nomenclature for varicella-zoster virus (VZV)
      clades was established, which is very useful in the monitoring of viral
      evolution, recombination, spread and genetic diversity. Currently, information
      about VZV clades has been disclosed worldwide, however, there are limited data
      regarding the characterization of circulating VZV clades in China, even where
      varicella remains widely epidemic. METHODS: From 2008 to 2012, clinical samples
      with varicella or zoster were collected in General Hospital in eight provinces
      and analyzed by PCR, restriction endonuclease digestion and sequencing. The viral
      clades were determined by analysis of five single nucleotide polymorphisms (SNPs)
      within the 447-bp fragment of open reading frame (ORF) 22, and the restriction
      fragment length polymorphisms (RFLPs) of ORF 38 (PstI), ORF 54 (BglI) and ORF 62
      (SmaI) were evaluated to understand genetic diversity of VZV and determinate
      varicella vaccine adverse event (VVAE). RESULTS: Seventy-seven varicella and 11
      zoster samples were identified as being positive for VZV. The five SNPs profile
      showed that the majority of VZV strains belonged to clade 2, but clade 5 and
      clade 4 strains were also found in Guangdong. The RFLPs analysis of the DNA
      fragments of ORF 38, 54 and 62 showed that 85 of these samples were characterized
      as PstI + BglI + SamI-, and the remaining three VZV strains from varicella
      patients were characterized as PstI-BglI + SamI+ which is the genetic profile of
      VVAEs. CONCLUSIONS: The study suggested that the predominant clade 2 VZVs had
      been continually circulating since at least the 1950s in China. Nearly all VZV
      strains except VVAEs possessed the genetic profile of PstI + BglI + Sam-.
      However, the other clades were also found to be co-circulating with clade 2,
      especially in the border regions. These results highlighted the need for the
      constant and broad use of virologic surveillance to provide an important genetic
      baseline for varicella control and vaccination programs in China.

PMID- 27717331
TI  - Characterization of eleven monosomic alien addition lines added from Gossypium
      anomalum to Gossypium hirsutum using improved GISH and SSR markers.
AB  - BACKGROUND: Gossypium anomalum (BB genome) possesses the desirable
      characteristics of drought tolerance, resistance to diseases and insect pests,
      and the potential for high quality fibers. However, it is difficult to transfer
      the genes associated with these desirable traits into cultivated cotton (G.
      hirsutum, AADD genome). Monosomic alien addition lines (MAALs) can be used as a
      bridge to transfer desired genes from wild species into G. hirsutum. In cotton,
      however, the high number and smaller size of the chromosomes has resulted in
      difficulties in discriminating chromosomes from wild species in cultivated cotton
      background, the development of cotton MAALs has lagged far behind many other
      crops. To date, no set of G. hirsutum-G. anomalum MAALs was reported. Here the
      amphiploid (AADDBB genome) derived from G. hirsutum * G. anomalum was used to
      generate a set of G. hirsutum-G. anomalum MAALs through a combination of
      consecutive backcrossing, genomic in situ hybridization (GISH), morphological
      survey and microsatellite marker identification. RESULTS: We improved the GISH
      technique used in our previous research by using a mixture of two probes from G.
      anomalum and G. herbaceum (AA genome). The results indicate that a ratio of 4:3
      (G. anomalum : G. herbaceum) is the most suitable for discrimination of
      chromosomes from G. anomalum and the At-subgenome of G. hirsutum. Using this
      improved GISH technique, 108 MAAL individuals were isolated. Next, 170 G.
      hirsutum- and G. anomalum-specific codominant markers were obtained and employed
      for characterization of these MAAL individuals. Finally, eleven out of 13 MAALs
      were identified. Unfortunately, we were unable to isolate Chrs. 1Ba and 5Ba due
      to their very low incidences in backcrossing generation, as these remained in a
      condition of multiple additions. CONCLUSIONS: The characterized lines can be
      employed as bridges for the transfer of desired genes from G. anomalum into G.
      hirsutum, as well as for gene assignment, isolation of chromosome-specific
      probes, development of chromosome-specific "paints" for fluorochrome-labeled DNA
      fragments, physical mapping, and selective isolation and mapping of cDNAs/genes
      for a particular G. anomalum chromosome.

PMID- 27717330
TI  - Role of vitamin D3 combined to alginates in preventing acid and oxidative injury
      in cultured gastric epithelial cells.
AB  - BACKGROUND: Gastric diseases are a worldwide problem in modern society, as
      reported in the USA, in the range of 0.5-2 episodes/year/person and an incidence
      of 5-100 episodes/1000/week according to seasons and age. There is convincing
      evidence that oxidative stress is involved in the pathogenesis of acute gastric
      injury. Acid secreted from gastric parietal cells determines mucosal injuries
      which in turn cause inflammation and oxidative stress. Consequent inflammation
      produces free radicals by mitochondria thus causing lipid peroxidation, oxidative
      and acidic stress, which can lead to cell apoptosis. Vitamin D3, the active form
      of vitamin D, may counteract intracellular cell death and improve epithelial
      regeneration. METHODS: This study was planned to assess whether vitamin D3 is a
      protective factor against acid injury and oxidative stress in gastric epithelial
      cells. Primary epithelial cells and GTL-16 cells have been used to test the
      effects of Grisu(r) alone or in combination with vitamin D3 during oxidative
      stress or high acid exposition measuring cell viability, ROS production, cellular
      adhesion time along with apoptotic, autophagic and survival pathways. The
      combined effect of Grisu(r) and vitamin D3 was found more effective in
      counteracting the negative consequences of oxidative stress and acidity
      conditions than some other gastroprotective agents, such as Maalox(r) or
      Gaviscon(r). RESULTS: In case of oxidative stress or acidity condition the
      stimulation with Grisu(r) alone caused an improvement of cell viability and a
      reduction of ROS production on epithelial gastric cells. In addition, the
      adhesion time of the cells was improved. All these effects were increased by the
      presence of vitamin D3. Similar data were also observed in primary gastric
      epithelial cells confirming the results obtained in GTL-16 cells. CONCLUSIONS:
      These results suggest that Grisu(r) in combination with vitamin D3 may exert a
      gastroprotective effect to maintain or restore the integrity of gastric
      epithelium through an antioxidant pathway, inhibiting apoptosis and activating
      survival kinases. Moreover, the combination of Grisu(r) and vitamin D3 improves
      cell viability and decreases ROS production compared to other gastroprotective
      agents combined with vitamin D3. All these data were validated using primary
      cells isolated from gastric tissue.

PMID- 27717332
TI  - Erratum to: Risk of cardiovascular events among patients with HIV treated with
      atazanavircontaining regimens: a retrospective cohort study.

PMID- 27717333
TI  - A household-based survey of knowledge, attitudes and practices towards dengue
      fever among local urban communities in Taiz Governorate, Yemen.
AB  - BACKGROUND: Yemen has witnessed several dengue fever outbreaks coincident with
      the social unrest and war in the country. The aim of the present study was to
      describe the knowledge, attitudes and practices (KAPs) of at-risk urban
      populations residing in Taiz, southwest of Yemen. In addition, factors possibly
      associated with poor preventive practices were investigated. METHODS: A household
      based, cross-sectional survey was conducted in three urban districts encompassing
      383 households. Data on the socio-demographic characteristics and KAPs of the
      participating household heads were collected using a pre-designed, structured
      questionnaire. The association of socio-demographic characteristics, knowledge
      and attitudes of the population with poor preventive practices against dengue
      fever was then analyzed using logistic regression. RESULTS: More than 90.0 % of
      respondent household heads had correct knowledge about fever, headache and joint
      pain as common signs and symptoms of dengue fever. Moreover, muscular pain and
      bleeding were perceived by more than 80.0 % of the respondents as being
      associated with dengue fever; however, only 65.0 % of the respondents reported
      skin rash as a sign of dengue fever. More than 95.0 % of respondents agreed about
      the seriousness and possible transmission of dengue fever; however, negative
      attitudes regarding the facts of being at risk of the disease and that the
      infection is preventable were expressed by 15.0 % of respondents. Despite the
      good level of knowledge and attitudes of the respondent population, poor
      preventive practices were common. Bivariate analysis identified poor knowledge of
      dengue signs and symptoms (OR = 2.1, 95 % CI = 1.24-3.68; P = 0.005) and its
      vector (OR = 2.1, 95 % CI = 1.14-3.84; P = 0.016) as factors significantly
      associated with poor preventive practices. However, multivariable analysis showed
      that poor knowledge of the vector is an independent predictor of poor preventive
      practices of the population (adjusted OR = 2.1, 95 % CI = 1.14-3.84; P = 0.018).
      CONCLUSION: The majority of people in urban communities of Taiz have a clear
      understanding of most signs/symptoms of dengue fever as well as positive
      attitudes towards the seriousness and possible transmissibility of dengue fever.
      However, negative attitudes regarding their perception of the risk and possible
      prevention of the infection are prevailing among a small proportion of the
      population and need to be targeted by educational campaigns. It appears that the
      good level of the population knowledge of the signs/symptoms of dengue fever and
      the factors contributing to the spread and control of its vectors did not
      translate into good practices.

PMID- 27717334
TI  - Early antibiotics administration during targeted temperature management after out
      of-hospital cardiac arrest: a nationwide database study.
AB  - BACKGROUND: Patients resuscitated after cardiac arrest are reportedly at high
      risk for infection and sepsis, especially those treated with targeted temperature
      management (TTM). There is, however, limited evidence suggesting that early
      antibiotic use improves patient outcomes. We examined the hypothesis that early
      treatment with antibiotics reduces mortality in patients with cardiac arrest
      receiving TTM. METHODS: We identified 2803 patients with cardiogenic out-of
      hospital cardiac arrest (OHCA) that were treated with TTM and were admitted to
      371 hospitals that contribute to the Japanese Diagnosis Procedure Combination
      inpatient database between July 2007 and March 2013. Of these, 1272 received
      antibiotics within the first 2 days (antibiotics) and 1531 did not (control). We
      generated 802 propensity score-matched pairs. RESULTS: There was no significant
      difference in 30-day mortality between the groups (control vs. antibiotics; 33.0
      % vs. 29.9 %; difference, 3.1 %; 95 % confidence interval [CI], -1.4 to 7.7 %, p
      = 0.18). Analysis using the hospital antibiotics prescribing rate as an
      instrumental variable showed that antibiotic use was not significantly associated
      with a reduction in 30-day mortality (6.6 %, CI 95 %, -0.5 to 13.7 %, p = 0.28).
      A subgroup analysis of patients who required extracorporeal membrane oxygenation
      (ECMO) indicated a significant difference in 30-day mortality between the 2
      groups (62.9 % vs. 43.5 %; difference 19.3 %, CI 95 %, 5.9 to 32.7 %, p = 0.005).
      In the instrumental variable model, the estimated reduction in 30-day mortality
      associated with antibiotics was 18.2 % (CI 95 %, 21.3 to 34.4 %, p = 0.03) in
      ECMO patients. CONCLUSIONS: Although there was no significant association between
      the use of antibiotics and mortality after overall cardiogenic OHCA treated with
      TTM, antibiotics may be beneficial in patients who require ECMO.

PMID- 27717335
TI  - With or without reirradiation in advanced local recurrent nasopharyngeal
      carcinoma: a case-control study.
AB  - BACKGROUND: The study aimed to evaluate the long-term outcome in patients with
      advanced local recurrent nasopharyngeal carcinoma (NPC) treated with or without
      reirradiation. METHODS: A total of 44 patients treated without reirradiation (non
      RT + chemotherapy) were matched with 44 patients treated with reirradiation (re
      RT+/-chemtherapy) by age, sex, Karnosky performance score (KPS), rT stage, rN
      stage, and time interval between initial radiation and recurrence (TI). Overall
      survival (OS) rate and time to progression (TTP) rate were assessed using Kaplan
      Meier method, log-rank test, and Cox regression analysis. RESULTS: From March
      2008 to December 2013, a total of 88 well-balanced rT3-4 N0-1 NPC patients were
      retrospectively analyzed. After a median follow-up of 27 months (range: 6-85),
      the 5-year OS rate and TTP rate was 23.4 %, 39.0 % in the non-RT + chemotherapy
      group and 27.5 %, 49.8 % in the re-RT+/-chemtherapy group, respectively.
      Multivariate analysis showed that significant toxic effect was the only
      significant prognosticator correlated with OS (HR: 2.15, 95 % CI = 1.02-4.53, p =
      0.044). No statistically significant survival differences were observed between
      the two treatment groups in either univariate or multivariate analyses.
      CONCLUSION: Compared with reiradiation, treating advanced local recurrent NPC
      with chemotherapy alone warrants further validation in the view of its similar
      survival and more acceptable toxicities.

PMID- 27717336
TI  - The protocol for a randomised-controlled trial of the evaluation of the tolerance
      and safety of early enteral nutrition in children after percutaneous endoscopic
      gastrostomy placement. (protocol version 09.01.2015).
AB  - BACKGROUND: The appropriate time to initiate enteral nutrition after the
      placement of a percutaneous endoscopic gastrostomy (PEG) tube has been an area of
      limited research. There are no sufficient randomised prospective controlled
      trials in the paediatric population comparing the safety and tolerance of early
      feeding (3 h) after PEG placement. In order to reduce the period of fasting,
      inadequate nutritional support, and hospitalisation time, we decided to devise
      this study. METHODS/DESIGN: This study is a multicentre, randomised, open-label
      trial designed to evaluate the tolerance and safety of early enteral nutrition
      after PEG placement in children. Patients are randomised to receive the first
      feeding bolus with a polymeric diet (1 kcal/ml) via a feeding tube 3 h after the
      PEG placement (group I - early enteral feeding) or 8 h after the procedure (group
      II - late enteral feeding). The key objective of the study is to compare the
      tolerance and safety of the early- and late-feeding modes after PEG placement in
      children. The primary endpoint is the number of patients who will achieve full
      feed (total fluid and caloric requirements) within 48 h of the first feeding
      bolus. The secondary endpoints are: the number of early and late complications,
      the duration of hospitalisation after PEG placement, gastric residuals (ml) total
      in the period up to 48 h since the first feeding bolus. DISCUSSION: To our
      knowledge this is the first study in paediatric patients to evaluate the
      tolerance and safety of early enteral nutrition after PEG placement. The goal is
      to establish an optimum standard procedure in the group of paediatric patients
      qualified for the PEG insertion procedure in Poland. TRIAL REGISTRATION:
      ClinicalTrials.gov ID NCT02777541 , registration date 05/18/2016.

PMID- 27717338
TI  - Estimation of axial curvature of anterior sclera: correlation between axial
      length and anterior scleral curvature as affected by angle kappa.
AB  - :  BACKGROUND: Though the development and fitting of scleral contact lenses are
      expanding steadily, there is  no simple method to provide scleral metrics for
      scleral contact lens fitting yet. The aim of this study was to establish formulae
      for estimation of the axial radius of curvature (ARC) of the anterior sclera
      using ocular biometric parameters that can be easily obtained with conventional
      devices. METHODS: A semi-automated stitching method and a computational analysis
      tool for calculating ARC were developed by using the ImageJ and MATLAB software.
      The ARC of all the ocular surface points were analyzed from the composite
      horizontal cross-sectional images of the right eyes of 24 volunteers; these
      measurements were obtained using anterior segment optical coherence tomography
      for a previous study (AS-OCT; Visante). Ocular biometric parameters were obtained
      from the same volunteers with slit-scanning topography and partial coherence
      interferometry. Correlation analysis was performed between the ARC at 8 mm to the
      axis line (ARC[8]) and other ocular parameters (including age). With ARC obtained
      on several nasal and temporal points (7.0, 7.5, 8.0, 8.5, and 9.0 mm from the
      axis line), univariate and multivariate linear regression analyses were performed
      to develop a model for estimating ARC with the help of ocular biometric
      parameters. RESULTS: Axial length, spherical equivalent, and angle kappa showed
      correlations with temporal ARC[8] (tARC[8]; Pearson's r = 0.653, -0.579, and 
      0.341; P = 0.001, 0.015, and 0.015, respectively). White-to-white corneal
      diameter (WTW) and anterior chamber depth (ACD) showed correlation with nasal
      ARC[8] (nARC[8]; Pearson's r = -0.492 and -0.461; P = 0.015 and 0.023,
      respectively). The formulae for estimating scleral curvatures (tARC, nARC, and
      average ARC) were developed as a function of axial length, ACD, WTW, and distance
      from the axis line, with good determinant power (72 - 80 %; SPSS ver. 22.0).
      Angle kappa showed strong correlation with axial length (Pearson's r = -0.813, P
      <0.001), and the different correlation patterns of nasal and temporal ARC with
      axial length can be explained by the ocular surface deviation represented by
      angle kappa. CONCLUSIONS: Axial length, ACD, and WTW are useful parameters for
      estimating the ARC of the anterior sclera, which is important for the haptic
      design of scleral contact lenses. Angle kappa affects the discrepancies between
      the nasal and temporal scleral curvature.

PMID- 27717337
TI  - Polymorphisms in the estrogen receptor alpha gene (ESR1), daily cycling estrogen
      and mammographic density phenotypes.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) involved in the estrogen
      pathway and SNPs in the estrogen receptor alpha gene (ESR1 6q25) have been linked
      to breast cancer development, and mammographic density is an established breast
      cancer risk factor. Whether there is an association between daily estradiol
      levels, SNPs in ESR1 and premenopausal mammographic density phenotypes is
      unknown. METHODS: We assessed estradiol in daily saliva samples throughout an
      entire menstrual cycle in 202 healthy premenopausal women in the Norwegian Energy
      Balance and Breast Cancer Aspects I study. DNA was genotyped using the Illumina
      Golden Gate platform. Mammograms were taken between days 7 and 12 of the
      menstrual cycle, and digitized mammographic density was assessed using a computer
      assisted method (Madena). Multivariable regression models were used to study the
      association between SNPs in ESR1, premenopausal mammographic density phenotypes
      and daily cycling estradiol. RESULTS: We observed inverse linear associations
      between the minor alleles of eight measured SNPs (rs3020364, rs2474148,
      rs12154178, rs2347867, rs6927072, rs2982712, rs3020407, rs9322335) and percent
      mammographic density (p-values: 0.002-0.026), these associations were strongest
      in lean women (BMI, <=23.6 kg/m2.). The odds of above-median percent mammographic
      density (>28.5 %) among women with major homozygous genotypes were 3-6 times
      higher than those of women with minor homozygous genotypes in seven SNPs. Women
      with rs3020364 major homozygous genotype had an OR of 6.46 for above-median
      percent mammographic density (OR: 6.46; 95 % Confidence Interval 1.61, 25.94)
      when compared to women with the minor homozygous genotype. These associations
      were not observed in relation to absolute mammographic density. No associations
      between SNPs and daily cycling estradiol were observed. However, we suggest,
      based on results of borderline significance (p values: 0.025-0.079) that the
      level of 17beta-estradiol for women with the minor genotype for rs3020364,
      rs24744148 and rs2982712 were lower throughout the cycle in women with low (<28.5
      %) percent mammographic density and higher in women with high (>28.5 %) percent
      mammographic density, when compared to women with the major genotype. CONCLUSION:
      Our results support an association between eight selected SNPs in the ESR1 gene
      and percent mammographic density. The results need to be confirmed in larger
      studies.

PMID- 27717340
TI  - Increasing comorbidity is associated with worsening physical function and pain
      after primary total knee arthroplasty.
AB  - BACKGROUND: Previous studies suggested that pre-operative comorbidity was a risk
      factor for worse outcomes after TKA. To our knowledge, studies have not examined
      whether postoperative changes in comorbidity impact pain and function outcomes
      longitudinally. Our objective was to examine if increasing comorbidity
      postoperatively is associated with worsening physical function and pain after
      primary total knee arthroplasty (TKA). METHODS: We performed a retrospective
      chart review of veterans who had completed Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) and Short Form-36 (SF36) surveys at
      regular intervals after primary TKA. Comorbidity was assessed using a variety of
      scales: validated Charlson comorbidity index score, and a novel Arthroplasty
      Comorbidity Severity Index score (Including medical index, local musculoskeletal
      index [including lower extremity and spine] and TKA-related index subscales;
      higher scores are worse ), at multiple time-points post-TKA. We used mixed model
      linear regression to examine the association of worsening comorbidity post-TKA
      with change in WOMAC and SF-36 scores in the subsequent follow-up periods,
      controlling for age, length of follow-up, and repeated observations. RESULTS: The
      study cohort consisted of 124 patients with a mean age of 71.7 years (range 58.6
      89.2, standard deviation (SD) 6.9) followed for a mean of 4.9 years post
      operatively (range 1.3-11.4; SD 2.8). We found that post-operative worsening of
      the Charlson Index score was significantly associated with worsening SF-36
      Physical Function (PF) (beta coefficient (beta) = -0.07; p < 0.0001), SF-36
      Bodily Pain (BP) (beta = -0.06; p = 0.002), and WOMAC PF subscale (beta = 0.08; p
      < 0.001; higher scores are worse) scores, in the subsequent periods. Worsening
      novel medical index subscale scores were significantly associated with worsening
      SF-36 PF scores (beta = -0.03; p = 0.002), SF-36 BP (beta = -0.04; p < 0.001) and
      showed a non-significant trend for worse WOMAC PF scores (beta = 0.02; p = 0.11)
      subsequently. Local musculoskeletal index subscale scores were significantly
      associated with worsening SF-36 PF (beta = -0.05; p = 0.001), SF-36 BP (beta = 
      0.04; p = 0.03) and WOMAC PF (beta = 0.06; p = 0.01) subsequently. None of the
      novel index subscale scores were significantly associated with WOMAC pain scores.
      TKA complications, as assessed by TKA-related index subscale,  were not
      significantly associated with SF-36 or WOMAC domain scores. CONCLUSIONS:
      Increasing Charlson index as well as novel medical and local musculoskeletal
      index subscale scores (from novel Arthroplasty  Comorbidity Severity Index) post
      TKA correlated with subsequent worsening of physical function and pain outcomes
      post-TKA. Further studies should examine which comorbidity management could have
      the greatest impact on these outcomes.

PMID- 27717341
TI  - Application of fundamental equations to species-area theory.
AB  - BACKGROUND: Species-area relationship (SAR), endemics-area relationship (EAR) and
      overlap-area relationship (OAR) are three important concepts in biodiversity
      study. The application of fundamental equations linking the SAR, EAR and OAR, can
      enrich the axiomatic framework of the species-area theory and deepen our
      understanding of the mechanisms of community assembly. RESULTS: Two fundamental
      equations are derived and extended to power law model and random replacement
      model of species-area distribution. Several important parameters, including the
      overlap index and extinction rate, are defined and expressed to enrich the
      species-area theory. For power law model, both EAR and OAR have three parameters,
      with one more parameter of the total area than SAR does. The EAR equation is a
      monotonically increasing function for parameter c and z, and a monotonically
      decreasing function for parameter A. The extinction rate, with two parameters, is
      a monotonically increasing function for parameter z, and a monotonically
      decreasing function for parameter A. The overlap index is a monotonically
      increasing function for parameter A, and a monotonically decreasing function for
      parameter z, independent of parameter c. CONCLUSIONS: The general formats of SAR,
      EAR, OAR, overlap index, overlap rate, sampling rate and extinction rate, are
      derived and extended to power law model and random replacement model as the
      axiomatic framework of species-area theory. In addition, if the total area is
      underestimated, the extinction rate will be overestimated.

PMID- 27717339
TI  - Refractive error characteristics in patients with congenital blepharoptosis
      before and after ptosis repair surgery.
AB  - BACKGROUND: We examined the effect of surgical repair on the pattern of
      refractive errors in Korean patients with congenital blepharoptosis. METHODS: We
      reviewed the clinical records of 54 patients with congenital blepharoptosis who
      attended our hospital from 2006 to 2012 and underwent a detailed refractive
      examination before and after ptosis repair surgery. Among them, 21 of the
      patients whose refractive data was available for both before and after the
      surgery were included in order to observe the effect of ptosis repair surgery on
      refractive error characteristics. The astigmatism groups were divided into three
      subgroups: with-the-rule (WTR), against-the-rule (ATR), and oblique astigmatism
      (OA). We also evaluated the severity of astigmatism. RESULTS: Before surgery, the
      ptotic eyes had more severe astigmatism and a greater percentage of OA than the
      fellow eyes. The changes in astigmatism magnitude before and after surgery were
      not significant, but the proportion of subjects with OA increased significantly.
      In ptotic eyes, amblyopia was found in 14 eyes (20.9 %). 3 eyes (4.5 %) were from
      solely occlusive visual stimulus deprivation due to severe ptosis, and 11 eyes
      were from refractive errors. Among refractive errors, amblyogenic astigmatism
      made up to the largest proportion of patients (8 patients, 11.9 %). CONCLUSIONS:
      Ptotic eyes had more severe astigmatism and more OA than fellow eyes. Amblyogenic
      astigmatism was more common in ptotic eyes. A change in astigmatism toward the OA
      axis was significantly detected after surgery, and that can be possible
      amblyogenic cause. Therefore, the correction of astigmatism before and after
      ptosis repair surgery is very important to prevent amblyopia.

PMID- 27717343
TI  - Factors associated with persons with disability employment in India: a cross
      sectional study.
AB  - BACKGROUND: Over twenty million persons with disability in India are increasingly
      being offered poverty alleviation strategies, including employment programs. This
      study employs a spatial analytic approach to identify correlates of employment
      among persons with disability in India, considering sight, speech, hearing,
      movement, and mental disabilities. METHODS: Based on 2001 Census data, this study
      utilizes linear regression and spatial autoregressive models to identify factors
      associated with the proportion employed among persons with disability at the
      district level. Models stratified by rural and urban areas were also considered.
      RESULTS: Spatial autoregressive models revealed that different factors contribute
      to employment of persons with disability in rural and urban areas. In rural
      areas, having mental disability decreased the likelihood of employment, while
      being female and having movement, or sight impairment (compared to other
      disabilities) increased the likelihood of employment. In urban areas, being
      female and illiterate decreased the likelihood of employment but having sight,
      mental and movement impairment (compared to other disabilities) increased the
      likelihood of employment. CONCLUSIONS: Poverty alleviation programs designed for
      persons with disability in India should account for differences in employment by
      disability types and should be spatially targeted. Since persons with disability
      in rural and urban areas have different factors contributing to their employment,
      it is vital that government and service-planning organizations account for these
      differences when creating programs aimed at livelihood development.

PMID- 27717344
TI  - Erratum to: Intellectual disability health content within medical curriculum: an
      audit of what our future doctors are taught.

PMID- 27717342
TI  - IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans.
AB  - BACKGROUND: The General Control Nonderepressible 2 (GCN2) kinase is a conserved
      member of the integrated stress response (ISR) pathway that represses protein
      translation and helps cells to adapt to conditions of nutrient shortage. As such,
      GCN2 is required for longevity and stress resistance induced by dietary
      restriction (DR). IMPACT is an ancient protein that inhibits GCN2. RESULTS: Here,
      we tested whether IMPACT down-regulation mimics the effects of DR in C. elegans.
      Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and
      increased lifespan and stress resistance of worms in a gcn-2-dependent manner.
      Impt-1 knockdown exacerbated DR-induced longevity and required several DR
      activated transcription factors to extend lifespan, among them SKN-1 and DAF-16,
      which were induced during larval development and adulthood, respectively, in
      response to impt-1 RNAi. CONCLUSIONS: IMPACT inhibits the ISR pathway, thus
      limiting the activation of stress response factors that are beneficial during
      aging and required under DR.

PMID- 27717345
TI  - Erratum to: Inequalities in the frequency of free sugars intake among Syrian 1
      year-old infants: a cross-sectional study.

PMID- 27717346
TI  - Identification and characterization of two CD4 alleles in Microminipigs.
AB  - BACKGROUND: We previously identified two phenotypes of CD4+ cells with and
      without reactions to anti-pig CD4 monoclonal antibodies by flow cytometry in a
      herd of Microminipigs. In this study, we analyzed the coding sequences of CD4 and
      certified the expression of CD4 molecules in order to identify the genetic
      sequence variants responsible for the positive and negative PBMCs reactivity to
      anti-pig CD4 monoclonal antibodies. RESULTS: We identified two CD4 alleles, CD4.A
      and CD4.B, corresponding to antibody positive and negative, respectively, by
      nucleotide sequencing of PCR products using CD4 specific primer pairs. In
      comparison with the swine CD4 amino-acid sequence [GenBank: NP_001001908], CD4.A
      had seven amino-acid substitutions and CD4.B had 15 amino-acid substitutions. The
      amino-acid sequences within domain 1 of CD4.B were identical to the swine CD4.2
      [GenBank: CAA46584] sequence that had been reported previously to be a modified
      CD4 molecule that had lost reactivity with an anti-pig CD4 antibody in NIH
      miniature pigs. Homozygous and heterozygous CD4.A and CD4.B alleles in the
      Microminipigs herd were characterised by using the RFLP technique with the
      restriction endonuclease, BseRI. The anti-pig CD4 antibody recognized pig PBMCs
      with CD4.AA and CD4.AB, but did not recognized those with CD4.BB. We transfected
      HeLa cells with the FLAG-tagged CD4.A or CD4.B vectors, and certified that
      transfected HeLa cells expressed FLAG in both vectors. The failure of cells to
      react with anti-CD4 antibodies in CD4.B pigs was associated to ten amino-acid
      substitutions in domain 1 and/or one amino-acid substitution in joining region 3
      of CD4.B. We also found exon 8 was defective in some CD4.A and CD4.B resulting in
      the loss of the transmembrane domain, which implies that these CD4 proteins are
      secreted from helper T cells into the circulation. CONCLUSIONS: We identified
      that amino-acids substitutions of domain 1 in CD4.B gave rise to the failure of
      some CD4 expressing cells to react with particular anti-pig CD4 monoclonal
      antibodies. In addition, we developed a PCR-RFLP method that enabled us to simply
      identify the CD4 sequence variant and the positive and negative PBMCs reactivity
      to our anti-pig CD4 monoclonal antibodies without the need to use flow cytometric
      analysis.

PMID- 27717348
TI  - Patterns of privilege: A total cohort analysis of admission and academic outcomes
      for Maori, Pacific and non-Maori non-Pacific health professional students.
AB  - BACKGROUND: Tertiary institutions are struggling to ensure equitable academic
      outcomes for indigenous and ethnic minority students in health professional
      study. This demonstrates disadvantaging of ethnic minority student groups
      (whereby Indigenous and ethnic minority students consistently achieve academic
      outcomes at a lower level when compared to non-ethnic minority students) whilst
      privileging non-ethnic minority students and has important implications for
      health workforce and health equity priorities. Understanding the reasons for
      academic inequities is important to improve institutional performance. This study
      explores factors that impact on academic success for health professional students
      by ethnic group. METHODS: Kaupapa Maori methodology was used to analyse data for
      2686 health professional students at the University of Auckland in 2002-2012.
      Data were summarised for admission variables: school decile, Rank Score, subject
      credits, Auckland school, type of admission, and bridging programme; and academic
      outcomes: first-year grade point average (GPA), first-year passed all courses,
      year 2 - 4 programme GPA, graduated, graduated in the minimum time, and composite
      completion for Maori, Pacific, and non-Maori non-Pacific (nMnP) students.
      Statistical tests were used to identify significant differences between the three
      ethnic groupings. RESULTS: Maori and Pacific students were more likely to attend
      low decile schools (27 % Maori, 33 % Pacific vs. 5 % nMnP, p < 0.01); complete
      bridging foundation programmes (43 % Maori, 50 % Pacific vs. 5 % nMnP, p < 0.01),
      and received lower secondary school results (Rank Score 197 Maori, 178 Pacific
      vs. 231 nMnP, p < 0.01) when compared with nMnP students. Patterns of privilege
      were seen across all academic outcomes, whereby nMnP students achieved higher
      first year GPA (3.6 Maori, 2.8 Pacific vs. 4.7 nMnP, p < 0.01); were more likely
      to pass all first year courses (61 % Maori, 41 % Pacific vs. 78 % nMnP, p <
      0.01); to graduate from intended programme (66 % Maori, 69 % Pacific vs. 78 %
      nMnP, p < 0.01); and to achieve optimal completion (9 % Maori, 2 % Pacific vs. 20
      % nMnP, p < 0.01) when compared to Maori and Pacific students. CONCLUSIONS: To
      meet health workforce and health equity goals, tertiary institution staff should
      understand the realities and challenges faced by Maori and Pacific students and
      ensure programme delivery meets the unique needs of these students. Ethnic
      disparities in academic outcomes show patterns of privilege and should be
      alarming to tertiary institutions. If institutions are serious about achieving
      equitable outcomes for Maori and Pacific students, major institutional changes
      are necessary that ensure the unique needs of Maori and Pacific students are met.

PMID- 27717347
TI  - Associations between musculoskeletal pain and work-related factors among public
      service sector computer workers in Kaunas County, Lithuania.
AB  - BACKGROUND: Information technologies in occupational activities have been
      developing very rapid. Epidemiological studies have shown that musculoskeletal
      disorders are widely prevalent among employees working with a computer. The aim
      of this study was to evaluate the prevalence of musculoskeletal pain in various
      anatomical areas and its associations with individual, ergonomic, and
      psychosocial factors among computer workers of the public sector in Kaunas
      County, Lithuania. METHODS: The investigation consisting of two parts -
      questionnaire study (Nordic Musculoskeletal Questionnaire and Copenhagen
      Psychosocial Questionnaire) and direct observation (evaluation of work ergonomics
      using the Rapid Upper Limb Assessment [RULA]) - was carried out in three randomly
      selected public sector companies of Kaunas County. The representative study
      sample comprised 513 public service office workers. The prevalence of
      musculoskeletal pain in five anatomical areas of the body (shoulders, elbows,
      wrists/hands, as well as upper and low back) was evaluated. RESULTS: The
      prevalence rates of shoulder, elbow, wrist/hand, upper and low back pain were
      50.5 %, 20.3 %, 26.3 %, 44.8 %, and 56.1 %, respectively. Individual factors such
      as gender, age, computer work experience, and body mass index were found as
      significant for musculoskeletal pain in various musculoskeletal regions. The
      respondents reporting pain in shoulder, wrist/hand, upper back, and low back
      areas had a statistically significantly higher mean RULA score. The duration of
      working with a computer was found as a significant factor for shoulder pain. High
      quantitative demands were related to musculoskeletal pain in all investigated
      anatomical areas expect for the low back; weak social support was a significant
      predictor for complaints in upper and low back areas. CONCLUSION: This study
      confirmed associations between musculoskeletal pain and work ergonomics;
      therefore, preventive measures at the workplace should be directed to the
      improvement in ergonomic work environment, education, and workload optimization.

PMID- 27717349
TI  - An efficient algorithm for identifying primary phenotype attractors of a large
      scale Boolean network.
AB  - BACKGROUND: Boolean network modeling has been widely used to model large-scale
      biomolecular regulatory networks as it can describe the essential dynamical
      characteristics of complicated networks in a relatively simple way. When we
      analyze such Boolean network models, we often need to find out attractor states
      to investigate the converging state features that represent particular cell
      phenotypes. This is, however, very difficult (often impossible) for a large
      network due to computational complexity. RESULTS: There have been some attempts
      to resolve this problem by partitioning the original network into smaller
      subnetworks and reconstructing the attractor states by integrating the local
      attractors obtained from each subnetwork. But, in many cases, the partitioned
      subnetworks are still too large and such an approach is no longer useful. So, we
      have investigated the fundamental reason underlying this problem and proposed a
      novel efficient way of hierarchically partitioning a given large network into
      smaller subnetworks by focusing on some attractors corresponding to a particular
      phenotype of interest instead of considering all attractors at the same time.
      Using the definition of attractors, we can have a simplified update rule with
      fixed state values for some nodes. The resulting subnetworks were small enough to
      find out the corresponding local attractors which can be integrated for
      reconstruction of the global attractor states of the original large network.
      CONCLUSIONS: The proposed approach can substantially extend the current limit of
      Boolean network modeling for converging state analysis of biological networks.

PMID- 27717350
TI  - Incidence of bovine neonatal pancytopenia in 243 farms in Germany.
AB  - BACKGROUND: Several research groups from different European countries have worked
      on the aetiopathogenesis of bovine neonatal pancytopenia (BNP) and an association
      between the use of the vaccine PregSure BVD (Pfizer, Germany) and the development
      of this haemorrhagic disease was confirmed. Because BNP is not a notifiable
      disease, it is difficult to obtain information on its incidence. Based on
      pharmacovigilance (PhV) data, which are the only officially available data at the
      national level, the incidence of BNP is considered low. However, voluntary
      reporting of the disease can lead to underreporting. To gain more insight into
      the incidence of BNP among the affected herds, an epidemiological study was
      performed, which focused on 243 farms in Germany with cases of BNP. Farmers were
      asked to report the occurrence of BNP, including the number of cases, which
      allowed calculation of incidence in the affected herds. Matching such data with
      the registered cases in the National PhV System (NPhVS) gave us an opportunity to
      assess the extent of BNP underreporting. RESULTS: On 243 farms, a total of 1195
      calves younger than 4 weeks with haemorrhagic diathesis were registered. In 58 %
      of the reports, a diagnosis of BNP was confirmed by blood analysis and or by
      necropsy. The number of cases observed on individual farms ranged from 1 to 80.
      Based on these results, the incidence of BNP on affected farms ranged from 0.3 to
      15.2 % (median 2.9 %). The maximal incidence in the year with the highest number
      of BNP calves ranged between 0.4 and 18.6 % (median 3.3 %). Comparing the number
      of cases registered in the NPhVS to the numbers found in this study revealed
      considerable underreporting to the national database: only 44 % of the farms and
      41 % of the BNP calves included in the study were registered in the NPhVS.
      CONCLUSIONS: In spite of the opportunity to report BNP calves to the Paul-Ehrlich
      Institut (Langen, Germany), the estimated number of undetected BNP cases is
      remarkably high. However, even if the revealed substantial underreporting is
      taken into account, the incidence of BNP is low. Nevertheless, the incidence on
      some affected farms is very high, resulting in considerable financial losses that
      should not be underestimated. Although the exact pathomechanism of BNP at the
      molecular level is still not known, its incidence is clearly declining following
      withdrawal of PregSure BVD from the market.

PMID- 27717351
TI  - Improvement in delivery of type 2 diabetes services differs by mode of care: a
      retrospective longitudinal analysis in the Aboriginal and Torres Strait Islander
      Primary Health Care setting.
AB  - BACKGROUND: Addressing evidence-practice gaps in primary care remains a
      significant public health challenge and is likely to require action at different
      levels of the health system. Whilst Continuous Quality Improvement (CQI) is
      associated with improvements in overall delivery, little is known about delivery
      of different types of care processes, and their relative improvement during CQI.
      METHODS: We used data from over 15,000 clinical audit records of clients with
      Type 2 diabetes collected as part of a wide-scale CQI program implemented between
      2005 and 2014 in 162 Aboriginal and Torres Strait Islander health centres. We
      abstracted data from clinical records on 15 service items recommended in clinical
      guidelines and categorised these items into five modes of care on the basis of
      the mechanism through which care is delivered: laboratory tests; generalist
      delivered physical checks; specialist-delivered checks; education/counselling for
      nutrition and physical activity and education/counselling for high risk substance
      use. We calculated delivery for each patient for each of mode of care by
      determining the proportion of recommended services delivered for that mode. We
      used multilevel regression models to quantify variation attributable to health
      centre or client level factors and to identify factors associated with greater
      adherence to clinical guidelines for each mode of care. RESULTS: Clients on
      average received 43 to 60 % of recommended care in 2005/6. Different modes of
      care showed different patterns of improvement. Generalist-delivered physical
      checks (delivered by a non-specialist) showed a steady year on year increase,
      delivery of laboratory tests showed improvement only in the later years of the
      study, and delivery of counselling/education interventions showed early
      improvement which then plateaued. Health centres participating in CQI had
      increased odds of top quartile service delivery for all modes compared to
      baseline, but effects differed by mode. Health centre factors explained 20-52 %
      of the variation across jurisdictions and health centres for different modes of
      care. CONCLUSIONS: Levels of adherence to clinical guidelines and patterns of
      improvement during participation in a CQI program differed for different modes of
      care. Policy and funding decisions may have had important effects on the level
      and nature of improvements achieved.

PMID- 27717352
TI  - Analyses of inter-rater reliability between professionals, medical students and
      trained school children as assessors of basic life support skills.
AB  - BACKGROUND: Training of lay-rescuers is essential to improve survival-rates after
      cardiac arrest. Multiple campaigns emphasise the importance of basic life support
      (BLS) training for school children. Trainings require a valid assessment to give
      feedback to school children and to compare the outcomes of different training
      formats. Considering these requirements, we developed an assessment of BLS skills
      using MiniAnne and tested the inter-rater reliability between professionals,
      medical students and trained school children as assessors. METHODS: Fifteen
      professional assessors, 10 medical students and 111-trained school children
      (peers) assessed 1087 school children at the end of a CPR-training event using
      the new assessment format. Analyses of inter-rater reliability (intraclass
      correlation coefficient; ICC) were performed. RESULTS: Overall inter-rater
      reliability of the summative assessment was high (ICC = 0.84, 95 %-CI: 0.84 to
      0.86, n = 889). The number of comparisons between peer-peer assessors (n = 303),
      peer-professional assessors (n = 339), and peer-student assessors (n = 191) was
      adequate to demonstrate high inter-rater reliability between peer- and
      professional-assessors (ICC: 0.76), peer- and student-assessors (ICC: 0.88) and
      peer- and other peer-assessors (ICC: 0.91). Systematic variation in rating of
      specific items was observed for three items between professional- and peer
      assessors. CONCLUSION: Using this assessment and integrating peers and medical
      students as assessors gives the opportunity to assess hands-on skills of school
      children with high reliability.

PMID- 27717353
TI  - Achieving universal health coverage in South Africa through a district health
      system approach: conflicting ideologies of health care provision.
AB  - BACKGROUND: Universal Health Coverage (UHC) has emerged as a major goal for
      health care delivery in the post-2015 development agenda. It is viewed as a
      solution to health care needs in low and middle countries with growing enthusiasm
      at both national and global levels. Throughout the world, however, the paths of
      countries to UHC have differed. South Africa is currently reforming its health
      system with UHC through developing a national health insurance (NHI) program.
      This will be practically achieved through a decentralized approach, the district
      health system, the main vehicle for delivering services since democracy. METHODS:
      We utilize a review of relevant documents, conducted between September 2014 and
      December 2015 of district health systems (DHS) and UHC and their ideological
      underpinnings, to explore the opportunities and challenges, of the district
      health system in achieving UHC in South Africa. RESULTS: Review of data from the
      NHI pilot districts suggests that as South Africa embarks on reforms toward UHC,
      there is a need for a minimal universal coverage and emphasis on district
      particularity and positive discrimination so as to bridge health inequities. The
      disparities across districts in relation to health profiles/demographics, health
      delivery performance, management of health institutions or district management
      capacity, income levels/socio-economic status and social determinants of health,
      compliance with quality standards and above all the burden of disease can only be
      minimised through positive discrimination by paying more attention to underserved
      and disadavantaged communities. CONCLUSIONS: We conclude that in South Africa the
      DHS is pivotal to health reform and UHC may be best achieved through minimal
      universal coverage with positive discrimination to ensure disparities across
      districts in relation to disease burden, human resources, financing and
      investment, administration and management capacity, service readiness and
      availability and the health access inequalities are consciously implicated. Yet
      ideological and practical issues make its achievement problematic.

PMID- 27717354
TI  - Establishment of an innovative staging system for extramedullary plasmacytoma.
AB  - BACKGROUND: Extramedullary plasmacytoma (EMP) is a rare malignant disease that
      lacks a unique clinical staging system to predict the survival of EMP patients
      and to design individualized treatment. Instead, clinicians have chosen to use
      the multiple myeloma (MM) staging system. METHODS: Forty-eight EMP patients
      treated between 1996 and 2014 were included in this study. The new clinical
      stages were established according to independent survival factors using Cox
      regression model. RESULTS: Lymph node metastasis and a larger primary tumor (>=5
      cm) were the only two independent poor prognostic factors for overall survival
      (OS) and disease-free survival (P < 0.05). Stage I was defined as the disease
      without those two poor prognostic factors. Stage II was defined as the presence
      of either factor, and Stage III was defined as the presence of both factors. OS
      was significantly different in each stage of the new staging system (P < 0.001),
      with a median follow-up time for Stage I, Stage II and Stage III of 68, 23 and 14
      months. The new staging system had enhanced prognostic value compared to the MM
      staging system (the area under ROC 0.763 versus 0.520, P = 0.044). Although no
      difference was observed between treatments in Stage I, the combination treatment
      was associated with a significantly beneficial OS in the late stages (5-year OS:
      15.3 % versus 79.5 %; P = 0.032). CONCLUSIONS: The new staging system exhibited a
      promising prognostic value for survival and could aid clinicians in choosing the
      most suitable treatment for EMP patients.

PMID- 27717355
TI  - Loss and conservation of evolutionary history in the Mediterranean Basin.
AB  - BACKGROUND: Phylogenetic diversity and evolutionary distinctiveness are highly
      valuable components of biodiversity, but they are rarely considered in
      conservation practices. Focusing on a biodiversity hotspot, the Mediterranean
      Basin, we aimed to identify those areas where evolutionary history is highly
      threatened and range-restricted in the region. Using null models, we first
      compared the spatial distributions of three indices: two measured threatened
      evolutionary history-Expected PDloss and Heightened Evolutionary distinctiveness
      and Global Endangerment-and one measured endemic evolutionary history
      Biogeographically Evolutionary Distinctiveness. We focused on three vertebrate
      groups with high proportions of endemic, threatened species: amphibians,
      squamates and terrestrial mammals. Second, we estimated the spatial overlap of
      hotspots of threatened and endemic evolutionary history within the network of
      protected areas under several conservation scenarios. RESULTS: Areas that
      concentrate evolutionary history of conservation interest greatly differed among
      taxa and indices, although a large proportion of hotspots were identified in the
      Maghreb, in the East of the Mediterranean Basin as well as in islands. We found
      that, in a minimum conservation scenario, there was a significant proportion of
      hotspots for amphibians and squamates that were protected but not for terrestrial
      mammals. However, in a strong conservation scenario, only few hotspots overlapped
      with protected areas and they were significantly less protected than in a model
      where hotspots were chosen randomly. CONCLUSIONS: Some sites concentrate highly
      threatened and range-restricted evolutionary history of the Mediterranean basin
      and their conservation could be much improved. These sites are relevant for
      conservation studies aimed at designing new conservation actions to preserve
      evolutionary history and the option values it represents.

PMID- 27717356
TI  - Estimating the costs for the treatment of abortion complications in two public
      referral hospitals: a cross-sectional study in Ouagadougou, Burkina Faso.
AB  - BACKGROUND: Treatment costs of induced abortion complications can consume a
      substantial amount of hospital resources. This use of hospitals scarce resources
      to treat induced abortion complications may affect hospitals' capacities to
      deliver other health care services. In spite of the importance of studying the
      burden of the treatment of induced abortion complications, few studies have been
      conducted to document the costs of treating abortion complications in Burkina
      Faso. Our objective was to estimate the costs of six abortion complications
      including incomplete abortion, hemorrhage, shock, infection/sepsis, cervix or
      vagina laceration, and uterus perforation treated in two public referral hospital
      facilities in Ouagadougou and the cost saving of providing safe abortion care
      services. METHODS: The distribution of abortion-related complications was
      assessed through a review of postabortion care-registers combined with interviews
      with key informants in maternity wards and in hospital facilities. Two structured
      questionnaires were used for data collection following the perspective of the
      hospital. The first questionnaire collected information on the units and the unit
      costs of drugs and medical supplies used in the treatment of each complication.
      The second questionnaire gathered information on salaries and overhead expenses.
      All data were entered in a spreadsheet designed for studying abortion, and
      analyses were performed on Excel 2007. RESULTS: Across six types of abortion
      complications, the mean cost per patient was USD45.86. The total cost to these
      two public referral hospital facilities for treating the complications of
      abortion was USD22,472.53 in 2010 equivalent to USD24,466.21 in 2015. Provision
      of safe abortion care services to women who suffered from complications of unsafe
      induced abortion and who received care in these public hospitals would only have
      cost USD2,694, giving potential savings of more than USD19,778.53 in that year.
      CONCLUSIONS: The treatment of the complications of abortion consumes a
      significant proportion (up to USD22,472.53) of the two public hospitals resources
      in Burkina Faso. Safe abortion care services may represent a cost beneficial
      alternative, as it may have saved USD19,778.53 in 2010.

PMID- 27717357
TI  - Perfusion index assessment during transition period of newborns: an observational
      study.
AB  - BACKGROUND: Perfusion index (PI) is becoming a part of clinical practice in
      neonatology to monitor peripheral perfusion noninvasively. Hemodynamic and
      respiratory changes occur in newborns during the transition period after birth in
      which peripheral perfusion may be affected. Tachypnea is a frequent symptom
      during this period. While some tachypneic newborns get well in less than 6 h and
      diagnosed as "delayed transition", others get admitted to intensive care unit
      which transient tachypnea of newborn (TTN) being the most common diagnosis among
      them. We aimed to compare PI of neonates with TTN and delayed transition with
      controls, and assess its value on discrimination of delayed transition and TTN.
      METHODS: Neonates with gestational age between 37 and 40 weeks who were born with
      elective caesarian section were included. Eligible neonates were monitored with
      Masimo Set Radical7 pulse-oximeter (Masimo Corp., Irvine, CA, USA). Postductal
      PI, oxygen saturation and heart rate were manually recorded every 10 s for 3 min
      for two defined time periods as 10th minute and 1st hour. Axillary temperature
      were also recorded. Newborn infants were grouped as control, delayed transition,
      and TTN. RESULTS: Forty-nine tachypneic (TTN; 21, delayed transition; 28) and 30
      healthy neonates completed the study. PI values were similar between three groups
      at both periods. There were no correlation between PI and respiratory rate, heart
      rate, and temperature. CONCLUSION: PI assessment in maternity unit does not
      discriminate TTN from delayed transitional period in newborns which may indicate
      that peripheral perfusion is not severely affected in either condition.

PMID- 27717358
TI  - smokeSALUD: exploring the effect of demographic change on the smoking prevalence
      at municipality level in Austria.
AB  - BACKGROUND: Reducing the smoking population is still high on the policy agenda,
      as smoking leads to many preventable diseases, such as lung cancer, heart
      disease, diabetes, and more. In Austria, data on smoking prevalence only exists
      at the federal state level. This provides an interesting overview about the
      current health situation, but for regional planning authorities these data are
      often insufficient as they can hide pockets of high and low smoking prevalence in
      certain municipalities. METHODS: This paper presents a spatial-temporal change of
      estimated smokers for municipalities from 2001 and 2011. A synthetic dataset of
      smokers is built by combining individual large-scale survey data and small area
      census data using a deterministic spatial microsimulation approach. Statistical
      analysis, including chi-square test and binary logistic regression, are applied
      to find the best variables for the simulation model and to validate its results.
      RESULTS: As no easy-to-use spatial microsimulation software for non-programmers
      is available yet, a flexible web-based spatial microsimulation application for
      health decision support (called simSALUD) has been developed and used for these
      analyses. The results of the simulation show in general a decrease of smoking
      prevalence within municipalities between 2001 and 2011 and differences within
      areas are identified. These results are especially valuable to policy decision
      makers for future planning strategies. CONCLUSIONS: This case study shows the
      application of smokeSALUD to model the spatial-temporal changes in the smoking
      population in Austria between 2001 and 2011. This is important as no data on
      smoking exists at this geographical scale (municipality). However, spatial
      microsimulation models are useful tools to estimate small area health data and to
      overcome these problems. The simulations and analysis should support health
      decision makers to identify hot spots of smokers and this should help to show
      where to spend health resources best in order to reduce health inequalities.

PMID- 27717359
TI  - Potential use of mobile phones in improving animal health service delivery in
      underserved rural areas: experience from Kilosa and Gairo districts in Tanzania.
AB  - BACKGROUND: Sub-optimal performance of the animal health delivery system in rural
      areas is common in developing countries including Tanzania. However, penetration
      of mobile phones and availability of good road network and public transport
      systems offer opportunities for improving the access of rural communities to
      diagnostic and advisory services from facilities and expertise located in urban
      areas. A questionnaire survey on possession and use of mobile phones by pastoral
      and agro-pastoral communities in Kilosa and Gairo districts was carried out
      between November and December 2015. A total number of 138 livestock keepers from
      three villages of Chakwale (54), Mvumi (41) and Parakuyo (43) participated in the
      study. An e-based system was designed and tested to link rural communities with
      urban diagnostic facilities. RESULTS: It was observed that the average number of
      phones possessed by individuals interviewed and household families was 1.1 +/-
      0.26 (1-2) and 3.5 +/- 2.23 (1-10), respectively. It was further observed that
      out of 138 livestock keepers interviewed, 133 (96.4 %) had feature phones while
      10 (7.2 %) of them possessed smartphones. Mobile phone is currently used to
      support livestock production by communicating on animal health in Parakuyo (18,
      41.9 %), Mvumi (18, 43.9 %) and Chakwale (14, 25.9 %). Other contributions of
      mobile phones in livestock and crop agriculture observed in the study area
      include: exchange of livestock price information, crop price information,
      communicating on plant health/diseases, livestock extension and advisory services
      as well as crop farming extension and advisory services. We also designed and
      tested an e-based SUAVetDiag(r) system to support timely diagnosis of infectious
      disease conditions and prompt advice on case management in veterinary underserved
      areas. CONCLUSIONS: Availability of mobile phones in rural areas, in combination
      with supporting infrastructure and facilities in urban areas, has potential to
      stimulate local development and improving delivery of animal health and extension
      services. It is recommended that more development and refinement of the system
      should be conducted to ensure that this potential is tapped to revolutionalise
      delivery of animal health services in rural areas.

PMID- 27717360
TI  - The effect of changing the built environment on physical activity: a quantitative
      review of the risk of bias in natural experiments.
AB  - BACKGROUND: Evidence regarding the association of the built environment with
      physical activity is influencing policy recommendations that advocate changing
      the built environment to increase population-level physical activity. However, to
      date there has been no rigorous appraisal of the quality of the evidence on the
      effects of changing the built environment. The aim of this review was to conduct
      a thorough quantitative appraisal of the risk of bias present in those natural
      experiments with the strongest experimental designs for assessing the causal
      effects of the built environment on physical activity. METHODS: Eligible studies
      had to evaluate the effects of changing the built environment on physical
      activity, include at least one measurement before and one measurement of physical
      activity after changes in the environment, and have at least one intervention
      site and non-intervention comparison site. Given the large number of systematic
      reviews in this area, studies were identified from three exemplar systematic
      reviews; these were published in the past five years and were selected to provide
      a range of different built environment interventions. The risk of bias in these
      studies was analysed using the Cochrane Risk of Bias Assessment Tool: for Non
      Randomized Studies of Interventions (ACROBAT-NRSI). RESULTS: Twelve eligible
      natural experiments were identified. Risk of bias assessments were conducted for
      each physical activity outcome from all studies, resulting in a total of fifteen
      outcomes being analysed. Intervention sites included parks, urban
      greenways/trails, bicycle lanes, paths, vacant lots, and a senior citizen's
      centre. All outcomes had an overall critical (n = 12) or serious (n = 3) risk of
      bias. Domains with the highest risk of bias were confounding (due to inadequate
      control sites and poor control of confounding variables), measurement of
      outcomes, and selection of the reported result. CONCLUSIONS: The present review
      focused on the strongest natural experiments conducted to date. Given this, the
      failure of existing studies to adequately control for potential sources of bias
      highlights the need for more rigorous research to underpin policy recommendations
      for changing the built environment to increase physical activity. Suggestions are
      proposed for how future natural experiments in this area can be improved.

PMID- 27717361
TI  - Effect of intraarticular inoculation of mesenchymal stem cells in dogs with hip
      osteoarthritis by means of objective force platform gait analysis: concordance
      with numeric subjective scoring scales.
AB  - BACKGROUND: Subjective pain assessment scales have been widely used for assessing
      lameness in response to pain, but the accuracy of these scales has been
      questioned. To assess scale accuracy, 10 lame, presa Canario dogs with
      osteoarthritis (OA) associated with bilateral hip dysplasia were first treated
      with mesenchymal stem cells. Then, potential lameness improvement was analyzed
      using two pain scales (Bioarth and visual analog scale). These data were compared
      with similar data collected using a force platform with the same animals during a
      period of 6 months after treatment. RESULTS: The F test for intraclass
      correlation showed that concordance in pain/lameness scores between the 2
      measuring methodologies was not significant (P value >= 0.9213; 95 % confidence
      interval, -0.56, 0.11). Although subjective pain assessment showed improvement
      after 6 months, force platform data demonstrated those same animals had returned
      to the initial lameness state. CONCLUSION: Use of pain assessment scales to
      measure lameness associated with OA did not have great accuracy and concordance
      when compared with quantitative force platform gait analysis.

PMID- 27717362
TI  - High genetic diversity among extraintestinal Escherichia coli isolates in pullets
      and layers revealed by a longitudinal study.
AB  - BACKGROUND: Various information about the genetic diversity of Escherichia coli
      isolates from chickens are available but a detailed epidemiological investigation
      based upon isolates obtained from interrelated pullet and layer flocks is still
      missing. Therefore, in the course of a longitudinal epidemiological study on
      pullets and layers, 144 E. coli isolates from chickens with or without
      pathological lesions of the reproductive tract were serotyped and genotyped with
      pulsed-field gel electrophoresis (PFGE). These isolates were collected during
      rearing, peak and at the end of production. The actual study is the first of its
      kind so as to elucidate genetic relatedness among extraintestinal E. coli
      isolated from chickens with varying pathological conditions in interrelated layer
      farms/flocks at different stages of rearing. RESULTS: Serotyping revealed that
      63.19 % of the isolates could not be assigned to any of the three serotypes
      tested whereas 30.55 % of the isolates belonged to serotype O1:K1, 4.86 % to
      O2:K1 and 1.38 % to O78:K80. After macrorestriction digest with XbaI, 91.66 % of
      the isolates were typeable resulting in 96 distinct PFGE profiles. Among them,
      five PFGE types included isolates collected from diseased chickens as well as
      from birds without pathological lesions. This finding shows that pathogenicity of
      E. coli in layers seems to be largely influenced by concurrent susceptibility
      factors. Furthermore, in six out of eight cases where two isolates were collected
      from each of eight birds, different PFGE types were found in the same or
      different organs of the same bird. The existence of predominant or persistent E.
      coli genotypes was only observed in two cases. CONCLUSIONS: It is concluded that
      extraintestinal E. coli genotypes and serotypes in pullets and layers are
      heterogenous and also do not maintain a single clonality within the same bird.
      The facts that E. coli strains did not show any definite clonal population
      structure based on geographical region, age of the host and pathological lesions
      should have relevance in further epidemiological studies and control strategies.

PMID- 27717363
TI  - Content-based analysis of Ki-67 stained meningioma specimens for automatic hot
      spot selection.
AB  - BACKGROUND: Hot-spot based examination of immunohistochemically stained
      histological specimens is one of the most important procedures in
      pathomorphological practice. The development of image acquisition equipment and
      computational units allows for the automation of this process. Moreover, a lot of
      possible technical problems occur in everyday histological material, which
      increases the complexity of the problem. Thus, a full context-based analysis of
      histological specimens is also needed in the quantification of
      immunohistochemically stained specimens. One of the most important reactions is
      the Ki-67 proliferation marker in meningiomas, the most frequent intracranial
      tumour. The aim of our study is to propose a context-based analysis of Ki-67
      stained specimens of meningiomas for automatic selection of hot-spots. METHODS:
      The proposed solution is based on textural analysis, mathematical morphology,
      feature ranking and classification, as well as on the proposed hot-spot gradual
      extinction algorithm to allow for the proper detection of a set of hot-spot
      fields. The designed whole slide image processing scheme eliminates such
      artifacts as hemorrhages, folds or stained vessels from the region of interest.
      To validate automatic results, a set of 104 meningioma specimens were selected
      and twenty hot-spots inside them were identified independently by two experts.
      The Spearman rho correlation coefficient was used to compare the results which
      were also analyzed with the help of a Bland-Altman plot. RESULTS: The results
      show that most of the cases (84) were automatically examined properly with two
      fields of view with a technical problem at the very most. Next, 13 had three such
      fields, and only seven specimens did not meet the requirement for the automatic
      examination. Generally, the Automatic System identifies hot-spot areas,
      especially their maximum points, better. Analysis of the results confirms the
      very high concordance between an automatic Ki-67 examination and the expert's
      results, with a Spearman rho higher than 0.95. CONCLUSION: The proposed hot-spot
      selection algorithm with an extended context-based analysis of whole slide images
      and hot-spot gradual extinction algorithm provides an efficient tool for
      simulation of a manual examination. The presented results have confirmed that the
      automatic examination of Ki-67 in meningiomas could be introduced in the near
      future.

PMID- 27717364
TI  - Meaningful engagement of people living with HIV who use drugs: methodology for
      the design of a Peer Research Associate (PRA) hiring model.
AB  - BACKGROUND: Community-based HIV, harm reduction, and addiction research
      increasingly involve members of affected communities as Peer Research Associates
      (PRAs)-individuals with common experiences to the participant population (e.g.
      people who use drugs, people living with HIV [PLHIV]). However, there is a
      paucity of literature detailing the operationalization of PRA hiring and thus
      limited understanding regarding how affected communities can be meaningfully
      involved through low-barrier engagement in paid positions within community-based
      participatory research (CBPR) projects. We aim to address this gap by describing
      a low-threshold PRA hiring process. RESULTS: In 2012, the BC Centre for
      Excellence in HIV/AIDS and the Dr. Peter AIDS Foundation collaborated to develop
      a mixed-method CBPR project evaluating the effectiveness of the Dr. Peter Centre
      (DPC)-an integrative HIV care facility in Vancouver, Canada. A primary objective
      of the study was to assess the impact of DPC services among clients who have a
      history of illicit drug use. In keeping with CBPR principles, affected
      populations, community-based organizations, and key stakeholders guided the
      development and dissemination of a low-barrier PRA hiring process to meaningfully
      engage affected communities (e.g. PLHIV who have a history of illicit drug use)
      in all aspects of the research project. The hiring model was implemented in a
      number of stages, including (1) the establishment of a hiring team; (2) the
      development and dissemination of the job posting; (3) interviewing applicants;
      and (4) the selection of participants. The hiring model presented in this paper
      demonstrates the benefits of hiring vulnerable PLHIV who use drugs as PRAs in
      community-based research. CONCLUSIONS: The provision of low-barrier access to
      meaningful research employment described herein attempts to engage affected
      communities beyond tokenistic involvement in research. Our hiring model was
      successful at engaging five PRAs over a 2-year period and fostered opportunities
      for future paid employment or volunteer opportunities through ongoing
      collaboration between PRAs and a diverse range of stakeholders working in
      HIV/AIDS and addictions. Additionally, this model has the potential to be used
      across a range of studies and community-based settings interested in meaningfully
      engaging communities in all stages of the research process.

PMID- 27717365
TI  - Severe active C3 glomerulonephritis triggered by immune complexes and inactivated
      after eculizumab therapy.
AB  - BACKGROUND: Understanding the role of alternative complement pathway
      dysregulation in membranoproliferative glomerulonephritis (MPGN) has led to a
      dramatic shift in its classification into two subgroups: immune complex-mediated
      MPGN and complement-mediated MPGN, consisting of dense deposit disease and C3
      glomerulonephritis (C3GN). A limited number of C3GN cases have been published to
      date with not yet conclusive results since the novel therapeutic approach with
      eculizumab was introduced. CASE PRESENTATION: We report the clinical follow-up of
      a 16-year-old patient in whom a diagnosis of C3GN was confirmed by
      immunofluorescence and electron microscopy in second and third kidney biopsies,
      while the first biopsy revealed idiopathic immune complex-mediated MPGN type III,
      Anders and Strife variant, which failed to improve after several attempts at
      conventional immunosuppression therapy. Although applied late in an already
      fairly advanced stage of the severe active form of MPGN, the efficacy of
      eculizumab on C3GN was evidenced clinically and pathohistologically. Its
      beneficial influence on pathomorphogenesis was demonstrated by a unique follow-up
      in the last three biopsies, despite the recent observation, confirmed in this
      study, of eculizumab binding within the kidney tissue. CONCLUSIONS: Clinicians
      and pathologists should be aware that, in some patients, an underlying genetic or
      acquired complement alternative pathway abnormality can be masked by an initial
      immune complex-mediated mechanism, which subsequently triggers an unbalanced
      excessive continual driving of complement terminal pathway activation and the
      development of C3GN. In such a patient, supplementary steroids in addition to
      eculizumab appear necessary to achieve an adequate response.

PMID- 27717366
TI  - A cross-sectional national survey assessing self-reported drug intake behavior,
      contact with the primary sector and drug treatment among service users of Danish
      drug consumption rooms.
AB  - BACKGROUND: Drug consumption rooms (DCRs) have been implemented worldwide as a
      harm-reducing strategy. In 2012, Denmark passed legislation allowing
      establishment of DCRs. The aim of this study was to identify characteristics and
      gain knowledge of the way service users use the DCRs including bridge building to
      specialized health care. Associations between nationality, opioid substitution
      treatment (OST), drug intake method, and response to staff advice on harm
      reducing education was investigated, as well as service user's reasons for using
      the DCRs, and their perceptions of safety and trust in the DCRs. METHODS: A
      survey questionnaire sampled 154 participants of DCRs. Convenience sampling was
      used. Key variables covered demographics, drug intake mode, educational advice
      received in the DCR, and opinions about and role of the DCRs for the service
      users. RESULTS: Only 10 % of the participants were under the age of 30, 30 %
      between 30 and 39 years, 36 % between 40 and 49 years, and 24 % age 50 or more. A
      total of 60 % of the participants had encountered drugs before they were 19 years
      old. Female participants were 25 %, and 73 % were Danish citizens, 8 % were non
      Danish EU citizens, and 18 % were non-EU citizens. As drug intake method, 63 %
      injected drugs in a vein, 7 % sniffed, and 37 % smoked. Of drugs used in the DCR,
      49 % used cocaine, 41 % heroin, 16 % a mix of heroin and cocaine, and 16 % used
      methadone. Participants who smoked drugs made significantly less use of drug
      rehabilitation than participants who sniffed or injected drugs. There was a
      similar rate of advice on OST across nationality. Participants accepted staff
      education on hygienic measures and safe injection practices and found it useful.
      Participants felt safe and trusted staff and bridge building to specialized
      health care took place in the DCR. CONCLUSIONS: Staff of Danish DCRs educate
      service users on health related issues and harm-reducing interventions. A
      subgroup who smoke and a subgroup of nationality other than Danish are
      underserved and have less likely been in OST. More research on these groups is
      needed.

PMID- 27717367
TI  - A multiplex urinary immunoassay for bladder cancer detection: analysis of a
      Japanese cohort.
AB  - BACKGROUND: Bladder cancer (BCa) is among the most commonly diagnosed
      malignancies worldwide, and due the high rate of post-operative disease
      recurrence, it is one of the most prevalent in many countries. The development of
      non-invasive molecular assays that can accurately detect and monitor BCa would be
      a major advance, benefiting both patients and healthcare systems. We have
      previously identified a urinary protein biomarker panel that is being developed
      for application in at-risk patient cohorts. Here, we investigated the potential
      utility of the multiplex assay in a Japanese cohort. METHODS: The Japanese study
      cohort collected from urology clinics at two institutions was comprised of a
      total of 288 subjects. The protein biomarker panel (IL8, MMP9, MMP10, ANG, APOE,
      SDC1, A1AT, PAI1, CA9, VEGFA) was monitored in voided urine samples collected
      prior to cystoscopy using a custom multiplex ELISA assay. The diagnostic
      performance of the biomarker panel was assessed using receiver operator curves,
      predictive modeling and descriptive statistics. RESULTS: Urinary biomarker
      concentrations were significantly elevated in cases versus controls, and in cases
      with high-grade and muscle-invasive tumors. The AUC for the 10-biomarker assay
      was 0.892 (95 % confidence interval 0.850-0.934), with an overall diagnostic
      sensitivity specificity of 0.85 and 0.81, respectively. A predictive model
      trained on the larger institutional cohort correctly identified 99 % of the cases
      from the second institution. CONCLUSIONS: Urinary levels of a 10-biomarker panel
      enabled discrimination of patients with BCa. The multiplex urinary diagnostic
      assay has the potential to be developed for the non-invasive detection of BCa in
      at-risk Japanese patients.

PMID- 27717368
TI  - Overview of harm reduction in prisons in seven European countries.
AB  - While the last decade has seen a growth of support for harm reduction around the
      world, the availability and accessibility of quality harm reduction services in
      prison settings is uneven and continues to be inadequate compared to the progress
      achieved in the broader community. This article provides a brief overview of harm
      reduction in prisons in Catalonia (Spain), Greece, Ireland, Italy, Latvia,
      Poland, and Portugal. While each country provides a wide range of harm reduction
      services in the broader community, the majority fail to provide these same
      services or the same quality of these services, in prison settings, in clear
      violation of international human rights law and minimum standards on the
      treatment of prisoners. Where harm reduction services have been available and
      easily accessible in prison settings for some time, better health outcomes have
      been observed, including significantly reduced rates of HIV and HCV incidence.
      While the provision of harm reduction in each of these countries' prisons varies
      considerably, certain key themes and lessons can be distilled, including around
      features of an enabling environment for harm reduction, resource allocation,
      collection of disaggregated data, and accessibility of services.

PMID- 27717370
TI  - Erratum to: Risk factors for mortality in patients admitted to intensive care
      units with pneumonia.

PMID- 27717369
TI  - Overexpression of AtOxR gene improves abiotic stresses tolerance and vitamin C
      content in Arabidopsis thaliana.
AB  - BACKGROUND: Abiotic stresses are serious threats to plant growth, productivity
      and result in crop loss worldwide, reducing average yields of most major crops.
      Although abiotic stresses might elicit different plant responses, most induce the
      accumulation of reactive oxygen species (ROS) in plant cells leads to oxidative
      damage. L-ascorbic acid (AsA, vitamin C) is known as an antioxidant and H2O2
      scavenger that defends plants against abiotic stresses. In addition, vitamin C is
      also an important component of human nutrition that has to be obtained from
      different foods. Therefore, increasing the vitamin C content is important for
      improving abiotic stresses tolerance and nutrition quality in crops production.
      RESULTS: Here, we show that the expression of AtOxR gene is response to multiple
      abiotic stresses (salt, osmotic, metal ion, and H2O2 treatment) in both the
      leaves and roots of Arabidopsis. AtOxR protein was localized to the Endoplasmic
      Reticulum (ER) in yeast and Arabidopsis cells by co-localization analysis with ER
      specific dye. AtOxR-overexpressing transgenic Arabidopsis plants enhance the
      tolerance to abiotic stresses. Overexpression of AtOxR gene resulted in AsA
      accumulation and decreased H2O2 content in transgenic plants. CONCLUSIONS: In
      this study, our results show that AtOxR responds to multiple abiotic stresses.
      Overexpressing AtOxR improves tolerance to abiotic stresses and increase vitamin
      C content in Arabidopsis thaliana. AtOxR will be useful for the improvement of
      important crop plants through moleculer breeding.

PMID- 27717371
TI  - Basic science of electronic cigarettes: assessment in cell culture and in vivo
      models.
AB  - Electronic cigarettes (e-cigarettes, ECIGs) were introduced into the market a
      decade ago as an alternative to tobacco smoking. Whether ECIGs are safe and
      whether they qualify as smoking cessation tool is currently unknown. Their use
      has markedly expanded in that period, despite the fact that potential toxic
      effects of the vapour created by the e-cigarette and the nicotine-containing
      cartridge fluid have been incompletely studied. Marketing targets diverse groups
      including older smokers but also young people. Whereas the adverse health effects
      of nicotine inhaled by users of ECIGs has been well documented, less is known
      about the other components. An increasing number of in vitro and in vivo studies
      demonstrate a range of adverse effects of both the vapour created by ECIGs as
      well as the nicotine-containing fluid. Importantly, these studies demonstrate
      that toxicity from ECIGs, although this may be less than that caused by tobacco
      products, not only arises from its nicotine content. Furthermore, there are no
      data on the long-term consequences of ECIG use. The wide range of ECIG products
      available to consumers and the lack of standardisation of toxicological
      approaches towards ECIG evaluation complicates the assessment of adverse health
      effects of their use. Here we review the current data on preclinical studies on
      ECIGs describing their effects in cell culture and animal models.

PMID- 27717373
TI  - DNA ligase IV syndrome; a review.
AB  - DNA ligase IV deficiency is a rare primary immunodeficiency, LIG4 syndrome, often
      associated with other systemic features. DNA ligase IV is part of the non
      homologous end joining mechanism, required to repair DNA double stranded breaks.
      Ubiquitously expressed, it is required to prevent mutagenesis and apoptosis,
      which can result from DNA double strand breakage caused by intracellular events
      such as DNA replication and meiosis or extracellular events including damage by
      reactive oxygen species and ionising radiation.Within developing lymphocytes, DNA
      ligase IV is required to repair programmed DNA double stranded breaks induced
      during lymphocyte receptor development.Patients with hypomorphic mutations in
      LIG4 present with a range of phenotypes, from normal to severe combined
      immunodeficiency. All, however, manifest sensitivity to ionising radiation.
      Commonly associated features include primordial growth failure with severe
      microcephaly and a spectrum of learning difficulties, marrow hypoplasia and a
      predisposition to lymphoid malignancy. Diagnostic investigations include
      immunophenotyping, and testing for radiosensitivity. Some patients present with
      microcephaly as a predominant feature, but seemingly normal immunity. Treatment
      is mainly supportive, although haematopoietic stem cell transplantation has been
      used in a few cases.

PMID- 27717372
TI  - Development of a programmed cell death ligand-1 immunohistochemical assay
      validated for analysis of non-small cell lung cancer and head and neck squamous
      cell carcinoma.
AB  - BACKGROUND: A high-quality programmed cell-death ligand 1 (PD-L1) diagnostic
      assay may help predict which patients are more likely to respond to anti
      programmed cell death-1 (PD-1)/PD-L1 antibody-based cancer therapy. Here we
      describe a PD-L1 immunohistochemical (IHC) staining protocol developed by Ventana
      Medical Systems Inc. and key analytical parameters of its use in formalin-fixed,
      paraffin-embedded (FFPE) samples of non-small cell lung cancer (NSCLC) and head
      and neck squamous cell carcinoma (HNSCC). METHODS: An anti-human PD-L1 rabbit
      monoclonal antibody (SP263) was optimized for use with the VENTANA OptiView DAB
      IHC Detection Kit on the automated VENTANA BenchMark ULTRA platform. The VENTANA
      PD-L1 (SP263) Assay was validated for use with FFPE NSCLC and HNSCC tissue
      samples in a series of studies addressing sensitivity, specificity, robustness,
      and precision. Samples from a subset of 181 patients from a Phase 1/2 study of
      durvalumab (NCT01693562) were analyzed to determine the optimal PD-L1 staining
      cut-off for enriching the probability of responses to treatment. The scoring
      algorithm was defined using statistical analysis of clinical response data from
      this clinical trial and PD-L1 staining parameters in HNSCC and NSCLC tissue.
      Inter-reader agreement was established by three pathologists who evaluated 81
      NSCLC and 100 HNSCC samples across the range of PD-L1 expression levels. RESULTS:
      The VENTANA PD-L1 (SP263) Assay met all pre-defined acceptance criteria. For both
      cancer types, a cut-off of 25 % of tumor cells with PD-L1 membrane staining of
      any intensity best discriminated responders from nonresponders. Samples with
      staining above this value were deemed to have high PD-L1 expression, and those
      with staining below it were deemed to have low or no PD-L1 expression. Inter
      reader agreement on PD-L1 status was 97 and 92 % for NSCLC and HNSCC,
      respectively. CONCLUSIONS: These results highlight the robustness and
      reproducibility of the VENTANA PD-L1 (SP263) Assay and support its suitability
      for use in the evaluation of NSCLC and HNSCC FFPE tumor samples using the devised
      >=25 % tumor cell staining cut-off in a clinical setting. The clinical utility of
      the PD-L1 diagnostic assay as a predictive biomarker will be further validated in
      ongoing durvalumab studies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01693562.

PMID- 27717374
TI  - The NSPCC UK Minding the Baby(r) (MTB) home-visiting programme, supporting young
      mothers (aged 14-25) in the first 2 years of their baby's life: study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: Young mothers living in low-income urban settings often are exposed
      to significant and chronic environmental difficulties including poverty, social
      isolation and poor education and typically also have to cope with personal
      histories of abuse and depression. Minding the Baby(r) (MTB) is an
      interdisciplinary home-visiting programme developed to support first-time young
      mothers, which integrates primary care and mental health approaches into a single
      intensive intervention from the last trimester of pregnancy until the child's
      second birthday. The primary aim of the intervention is to promote caregiver
      sensitivity, and, secondarily, to promote both child and maternal socioemotional
      outcomes. METHODS/DESIGN: This is a multisite randomised controlled trial (RCT)
      with a target recruitment of 200 first-time adolescent mothers (under 26 years of
      age). One hundred participants will be randomised to the MTB group and they will
      receive the MTB programme in addition to the usual services available in their
      areas. Those participants not allocated to MTB will receive Treatment as Usual
      (TAU) only. Researchers will carry out blind assessments at baseline (before the
      birth of the baby), and outcome assessments around the child's first and second
      birthdays. The primary outcome will be the quality of maternal sensitivity and
      the secondary outcomes will focus on attachment security, child
      cognitive/language development, behavioural problems, postponed childbearing,
      maternal mental health and incidents of child protection interventions.
      DISCUSSION: This study evaluates the Minding the Baby(r) programme in the UK. In
      particular, this RCT explores the effectiveness of this integrative approach,
      which focusses on maternal mental issues as well as parent-infant interaction,
      parental concerns and developmental outcomes. TRIAL REGISTRATION: ISRCTN08678682
      (date of registration 3 April 2014).

PMID- 27717375
TI  - pGluAbeta increases accumulation of Abeta in vivo and exacerbates its toxicity.
AB  - Several species of beta-amyloid peptides (Abeta) exist as a result of
      differential cleavage from amyloid precursor protein (APP) to yield various C
      terminal Abeta peptides. Several N-terminal modified Abeta peptides have also
      been identified in Alzheimer's disease (AD) brains, the most common of which is
      pyroglutamate-modified Abeta (AbetapE3-42). AbetapE3-42 peptide has an increased
      propensity to aggregate, appears to accumulate in the brain before the appearance
      of clinical symptoms of AD, and precedes Abeta1-42 deposition. Moreover, in vitro
      studies have shown that AbetapE3-42 can act as a seed for full length Abeta1-42.
      In this study, we characterized the Drosophila model of AbetapE3-42 toxicity by
      expressing the peptide in specific sets of neurons using the GAL4-UAS system, and
      measuring different phenotypic outcomes. We found that AbetapE3-42 peptide had an
      increased propensity to aggregate. Expression of AbetapE3-42 in the neurons of
      adult flies led to behavioural dysfunction and shortened lifespan. Expression of
      AbetapE3-42 constitutively in the eyes led to disorganised ommatidia, and
      activation of the c-Jun N-terminal kinase (JNK) signaling pathway. The eye
      disruption was almost completely rescued by co-expressing a candidate Abeta
      degrading enzyme, neprilysin2. Furthermore, we found that neprilysin2 was capable
      of degrading AbetapE3-42. Also, we tested the seeding hypothesis for AbetapE3-42
      in vivo, and measured its effect on Abeta1-42 levels. We found that Abeta1-42
      levels were significantly increased when Abeta1-42 and AbetapE3-42 peptides were
      co-expressed. Furthermore, we found that AbetapE3-42 enhanced Abeta1-42 toxicity
      in vivo. Our findings implicate AbetapE3-42 as an important source of toxicity in
      AD, and suggest that its specific degradation could be therapeutic.

PMID- 27717376
TI  - Rapid and efficient generation of neural progenitors from adult bone marrow
      stromal cells by hypoxic preconditioning.
AB  - BACKGROUND: Bone marrow stromal cells (BMSCs) are attractive as a source of
      neural progenitors for ex vivo generation of neurons and glia. Limited numbers of
      this subpopulation, however, hinder translation into autologous cell-based
      therapy. Here, we demonstrate rapid and efficient conditioning with hypoxia to
      enrich for these neural progenitor cells prior to further expansion in
      neurosphere culture. METHOD: Adherent cultures of BMSCs (rat/human) were
      subjected to 1 % oxygen for 24 h and then subcultured as neurospheres with
      epidermal growth factor (EGF) and basic fibroblast growth factor supplementation.
      Neurospheres and cell progeny were monitored immunocytochemically for marker
      expression. To generate Schwann cell-like cells, neurospheres were plated out and
      exposed to gliogenic medium. The resulting cells were co-cultured with purified
      dorsal root ganglia (rat) neurons and then tested for commitment to the Schwann
      cell fate. Fate-committed Schwann cells were subjected to in vitro myelination
      assay. RESULTS: Transient hypoxic treatment increased the size and number of
      neurospheres generated from both rat and human BMSCs. This effect was EGF
      dependent and attenuated with the EGF receptor inhibitor erlotinib. Hypoxia did
      not affect the capacity of neurospheres to generate neuron- or glia-like
      precursors. Human Schwann cell-like cells generated from hypoxia-treated BMSCs
      demonstrated expression of S100beta /p75 and capacity for myelination in vitro.
      CONCLUSION: Enhancing the yield of neural progenitor cells with hypoxic
      preconditioning of BMSCs in vitro but without inherent risks of genetic
      manipulation provides a platform for upscaling production of neural cell
      derivatives for clinical application in cell-based therapy.

PMID- 27717378
TI  - Worst case optimization for interfractional motion mitigation in carbon ion
      therapy of pancreatic cancer.
AB  - INTRODUCTION: The efficacy of radiation therapy treatments for pancreatic cancer
      is compromised by abdominal motion which limits the spatial accuracy for dose
      delivery - especially for particles. In this work we investigate the potential of
      worst case optimization for interfractional offline motion mitigation in carbon
      ion treatments of pancreatic cancer. METHODS: We implement a worst case
      optimization algorithm that explicitly models the relative biological
      effectiveness of carbon ions during inverse planning. We perform a comparative
      treatment planning study for seven pancreatic cancer patients. Treatment plans
      that have been generated using worst case optimization are compared against (1)
      conventional intensity-modulated carbon ion therapy, (2) single field uniform
      dose carbon ion therapy, and (3) an ideal yet impractical scenario relying on
      daily re-planning. The dosimetric quality and robustness of the resulting
      treatment plans is evaluated using reconstructions of the daily delivered dose
      distributions on fractional control CTs. RESULTS: Idealized daily re-planning
      consistently gives the best dosimetric results with regard to both target
      coverage and organ at risk sparing. The absolute reduction of D 95 within the
      gross tumor volume during fractional dose reconstruction is most pronounced for
      conventional intensity-modulated carbon ion therapy. Single field uniform dose
      optimization exhibits no substantial reduction for six of seven patients and
      values for D 95 for worst case optimization fall in between. The treated volume
      (D>95 % prescription dose) outside of the gross tumor volume is reduced by a
      factor of two by worst case optimization compared to conventional optimization
      and single field uniform dose optimization. Single field uniform dose
      optimization comes at an increased radiation exposure of normal tissues, e.g. ~2
      Gy (RBE) in the mean dose in the kidneys compared to conventional and worst case
      optimization and ~4 Gy (RBE) in D 1 in the spinal cord compared to worst case
      optimization. CONCLUSION: Interfractional motion substantially deteriorates dose
      distributions for carbon ion treatments of pancreatic cancer patients. Single
      field uniform dose optimization mitigates the negative influence of motion on
      target coverage at an increased radiation exposure of normal tissue. Worst case
      optimization enables an exploration of the trade-off between robust target
      coverage and organ at risk sparing during inverse treatment planning beyond
      margin concepts.

PMID- 27717377
TI  - Immune response in peripheral axons delays disease progression in SOD1G93A mice.
AB  - BACKGROUND: Increasing evidence suggests that the immune system has a beneficial
      role in the progression of amyotrophic lateral sclerosis (ALS) although the
      mechanism remains unclear. Recently, we demonstrated that motor neurons (MNs) of
      C57SOD1G93A mice with slow disease progression activate molecules classically
      involved in the cross-talk with the immune system. This happens a lot less in
      129SvSOD1G93A mice which, while expressing the same amount of transgene, had
      faster disease progression and earlier axonal damage. The present study
      investigated whether and how the immune response is involved in the preservation
      of motor axons in the mouse model of familial ALS with a more benign disease
      course. METHODS: First, the extent of axonal damage, Schwann cell proliferation,
      and neuromuscular junction (NMJ) denervation were compared between the two ALS
      mouse models at the disease onset. Then, we compared the expression levels of
      different immune molecules, the morphology of myelin sheaths, and the presence of
      blood-derived immune cell infiltrates in the sciatic nerve of the two SOD1G93A
      mouse strains using immunohistochemical, immunoblot, quantitative reverse
      transcription PCR, and rotating-polarization Coherent Anti-Stokes Raman
      Scattering techniques. RESULTS: Muscle denervation, axonal dysregulation, and
      myelin disruption together with reduced Schwann cell proliferation are prominent
      in 129SvSOD1G93A compared to C57SOD1G93A mice at the disease onset, and this
      correlates with a faster disease progression in the first strain. On the
      contrary, a striking increase of immune molecules such as CCL2, MHCI, and C3 was
      seen in sciatic nerves of slow progressor C57SOD1G93A mice and this was
      accompanied by heavy infiltration of CD8+ T lymphocytes and macrophages. These
      phenomena were not detectable in the peripheral nervous system of fast
      progressing mice. CONCLUSIONS: These data show for the first time that damaged
      MNs in SOD1-related ALS actively recruit immune cells in the peripheral nervous
      system to delay muscle denervation and prolong the lifespan. On the contrary, the
      lack of this response has a negative impact on the disease course.

PMID- 27717380
TI  - Local versus intravenous injections of skeletal muscle precursor cells in
      nonhuman primates with acute or chronic intrinsic urinary sphincter deficiency.
AB  - BACKGROUND: Many factors may influence the efficacy of cell therapy for intrinsic
      urinary sphincter deficiency (ISD), including the route of administration of the
      cells and the condition of the sphincter. The goal of this study was to compare
      local versus intravenous administration of autologous skeletal muscle precursor
      cells (skMPCs) when administered to nonhuman primates (NHPs) with either acute or
      chronic ISD. METHODS: Thirty-two adult female monkeys were divided into eight
      groups (n = 4/group): (1) control; (2) surgically induced ISD/no treatment; (3)
      acute ISD (6-week duration)/local vehicle only; (4) acute ISD/local skMPC
      injection; (5) acute ISD/systemic skMPC; (6) chronic ISD (6-month duration)/local
      vehicle; (7) chronic ISD/local skMPC; (8) chronic ISD/systemic skMPC. Maximal
      urethral pressures (MUP) were measured prior to ISD, prior to treatment and at 3
      and 6 months following treatment. Quantitative histology was used to measure
      muscle/collagen content, somatic innervation, and vascularity of the sphincter
      complexes. RESULTS: In NHPs with acute ISD both systemic and local administration
      of skMPCs increased resting MUP values and sphincter muscle content (p < 0.05 vs.
      ISD/vehicle). However, the effects of systemic skMPC administration were
      significantly lower than those of local injection (p > 0.05). In NHPs with
      chronic ISD local skMPC administration had reduced (compared to NHPs with acute
      ISD) effects on MUP and sphincter muscle values (p < 0.05 vs. acute ISD/skMPC);
      systemic administration had no effect. Pudendal nerve-stimulated increases in MUP
      were significant only in acute ISD NHPs with local skMPC treatment (p < 0.05 vs.
      resting MUP). The extent of sphincter vascularization and innervation were
      directly related to MUP and sphincter muscle content. CONCLUSIONS: Both the
      chronicity of ISD and the route of cell injection influence the efficacy of cell
      therapy in monkey models of ISD. This may be related to the relative ability of
      cells to stimulate vascularization and re-innervation in these different
      treatment conditions.

PMID- 27717379
TI  - Biohybrid cochlear implants in human neurosensory restoration.
AB  - BACKGROUND: The success of cochlear implantation may be further improved by
      minimizing implantation trauma. The physical trauma of implantation and
      subsequent immunological sequelae can affect residual hearing and the viability
      of the spiral ganglion. An ideal electrode should therefore decrease post
      implantation trauma and provide support to the residual spiral ganglion
      population. Combining a flexible electrode with cells producing and releasing
      protective factors could present a potential means to achieve this. Mononuclear
      cells obtained from bone marrow (BM-MNC) consist of mesenchymal and hematopoietic
      progenitor cells. They possess the innate capacity to induce repair of
      traumatized tissue and to modulate immunological reactions. METHODS: Human bone
      marrow was obtained from the patients that received treatment with biohybrid
      electrodes. Autologous mononuclear cells were isolated from bone marrow (BM-MNC)
      by centrifugation using the RegenlabTM THT-centrifugation tubes. Isolated BM-MNC
      were characterised using flow cytometry. In addition, the release of cytokines
      was analysed and their biological effect tested on spiral ganglion neurons
      isolated from neonatal rats. Fibrin adhesive (TissealTM) was used for the coating
      of silicone-based cochlear implant electrode arrays for human use in order to
      generate biohybrid electrodes. Toxicity of the fibrin adhesive and influence on
      insertion, as well on the cell coating, was investigated. Furthermore, biohybrid
      electrodes were implanted in three patients. RESULTS: Human BM-MNC release
      cytokines, chemokines, and growth factors that exert anti-inflammatory and
      neuroprotective effects. Using fibrin adhesive as a carrier for BM-MNC, a simple
      and effective cell coating procedure for cochlear implant electrodes was
      developed that can be utilised on-site in the operating room for the generation
      of biohybrid electrodes for intracochlear cell-based drug delivery. A safety
      study demonstrated the feasibility of autologous progenitor cell transplantation
      in humans as an adjuvant to cochlear implantation for neurosensory restoration.
      CONCLUSION: This is the first report of the use of autologous cell
      transplantation to the human inner ear. Due to the simplicity of this procedure,
      we hope to initiate its widespread utilization in various fields.

PMID- 27717381
TI  - Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole
      genome DNA methylation profiling.
AB  - BACKGROUND: In recent years the Illumina HumanMethylation450 (HM450) BeadChip has
      provided a user-friendly platform to profile DNA methylation in human samples.
      However, HM450 lacked coverage of distal regulatory elements. Illumina have now
      released the MethylationEPIC (EPIC) BeadChip, with new content specifically
      designed to target these regions. We have used HM450 and whole-genome bisulphite
      sequencing (WGBS) to perform a critical evaluation of the new EPIC array
      platform. RESULTS: EPIC covers over 850,000 CpG sites, including >90 % of the
      CpGs from the HM450 and an additional 413,743 CpGs. Even though the additional
      probes improve the coverage of regulatory elements, including 58 % of FANTOM5
      enhancers, only 7 % distal and 27 % proximal ENCODE regulatory elements are
      represented. Detailed comparisons of regulatory elements from EPIC and WGBS show
      that a single EPIC probe is not always informative for those distal regulatory
      elements showing variable methylation across the region. However, overall data
      from the EPIC array at single loci are highly reproducible across technical and
      biological replicates and demonstrate high correlation with HM450 and WGBS data.
      We show that the HM450 and EPIC arrays distinguish differentially methylated
      probes, but the absolute agreement depends on the threshold set for each
      platform. Finally, we provide an annotated list of probes whose signal could be
      affected by cross-hybridisation or underlying genetic variation. CONCLUSION: The
      EPIC array is a significant improvement over the HM450 array, with increased
      genome coverage of regulatory regions and high reproducibility and reliability,
      providing a valuable tool for high-throughput human methylome analyses from
      diverse clinical samples.

PMID- 27717382
TI  - Discovery of immunodominant T-cell epitopes reveals penton protein as a second
      immunodominant target in human adenovirus infection.
AB  - BACKGROUND: Human adenovirus (HAdV) infections remain a significant cause of
      morbidity and mortality after hematopoietic stem cell transplantation (HSCT).
      Efficient antiviral T-cell responses are necessary to clear infection, which is
      hampered by delayed immune reconstitution and medical immunosuppression after
      HSCT. Protective immunity may be conferred by adoptive transfer of HAdV-specific
      T cells. For identification of patients at risk and monitoring of treatment
      responses diligent assessment of anti-HAdV cellular immune responses is crucial.
      The HAdV-derived protein hexon has been recognized as a major immunodominant
      target across HAdV species. We aimed at identifying further targets of protective
      anti-HAdV immune response and characterizing immunogenic epitopes. METHODS:
      Nineteen candidate nonamers from hexon and penton proteins were identified by
      epitope binding prediction. Peptides were synthesized and tested for in vivo
      immunogenicity by screening peripheral blood mononuclear cells from healthy
      volunteers (n = 64) and HAdV-infected stem cell recipients (n = 26) for memory T
      cells recognizing the candidate epitopes in the context of most common HLA
      alleles. RESULTS: Functional CD8+ T cells recognizing seven epitopes were
      identified, among them four penton-derived and two hexon-derived peptides. The
      HLA-A*01-restricted penton-derived peptide STDVASLNY (A01PentonSTDV) and HLA-A*02
      restricted hexon-derived peptide TLLYVLFEV (A02HexonTLLY) were recognized by more
      than half of the persons carrying the respective HLA-type. CONCLUSIONS: Thus, the
      HAdV-derived penton protein is a novel major target of the anti-HAdV immune
      response. Identification of new immunodominant epitopes will facilitate and
      broaden immune assessment strategies to identify patients suitable for T-cell
      transfer. Knowledge of additional target structures may increase T-cell recovery
      in manufacturing processes.

PMID- 27717383
TI  - Left ventricular diastolic function is strongly correlated with active emptying
      of the left atrium: a novel analysis using three-dimensional echocardiography.
AB  - BACKGROUND: Increased left atrial (LA) dimensions are known to be a risk factor
      in predicting cardiovascular events and mortality and to be one key diagnostic
      tool to assess diastolic dysfunction. Currently, LA measurements are usually
      conducted using 2D-echocardiography, although there are well-known limitations.
      Real-time 3D-echocardiography is able to overcome these limitations, furthermore
      being a valid measurement tool compared to reference standards (e.g. cardiac
      magnetic resonance imaging). We investigated LA function and volume and their
      association to left ventricular (LV) diastolic function, using newly designed and
      validated software for 3D-echocardiographic analysis. This software is the first
      to allow for a sophisticated analysis of both passive and active LA emptying.
      METHODS: We analyzed 2D- and 3D-echocardiographic measurements of LA volume and
      function in 56 subjects and compared the results between patients with normal LV
      diastolic function (NDF) (n = 30, 52 +/- 15 years, BMI 24.7 +/- 2.6 kg/m2) and
      patients in which diastolic dysfunction (DDF) was suspected (n = 26, 65 +/- 9
      years, BMI 26.7 +/- 3.7 kg/m2). RESULTS: Volumes during LA active emptying were
      significantly smaller in DDF compared to NDF (active atrial stroke volume (ASV):
      3.0 (0.1-4.5) vs. 5.5 (2.7-7.8) ml, p = 0.005; True-EF: 7.3(0.1-11.5) vs. 16.2
      (8.1-25.4) %, p = 0.002). Furthermore, ASV showed a stronger association to
      E/e'mean than all other measured LA volumes (beta = - 0.35, p = 0.008). Neither
      total stroke LA volume, nor maximum or minimum LA volume differed significantly
      between the groups. CONCLUSIONS: Diastolic LV dysfunction results in a reduction
      in active LA emptying, which is more strongly associated with LV filling pressure
      than other previously investigated LA parameters.

PMID- 27717384
TI  - Preoperative plasma growth-differentiation factor-15 for prediction of acute
      kidney injury in patients undergoing cardiac surgery.
AB  - BACKGROUND: Growth-differentiation factor-15 (GDF-15) is an emerging humoral
      marker for risk stratification in cardiovascular disease. Cardiac-surgery
      associated acute kidney injury (CSA-AKI), an important complication in patients
      undergoing cardiac surgery, is associated with poor prognosis. The present
      secondary analysis of an observational cohort study aimed to determine the role
      of GDF-15 in predicting CSA-AKI compared with the Cleveland-Clinic Acute Renal
      Failure (CC-ARF) score and a logistic regression model including variables
      associated with renal dysfunction. METHODS: Preoperative plasma GDF-15 was
      determined in 1176 consecutive patients undergoing elective cardiac surgery.
      Patients with chronic kidney disease stage 5 were excluded. AKI was defined
      according to Kidney-Disease-Improving-Global-Outcomes (KDIGO) - creatinine
      criteria. The following variables were screened for association with development
      of postoperative AKI: age, gender, additive Euroscore, serum creatinine, duration
      of cardiopulmonary bypass, duration of surgery, type of surgery, total
      circulatory arrest, preoperative hemoglobin, preoperative oxygen-supplemented
      cerebral oxygen saturation, diabetes mellitus, hemofiltration during ECC, plasma
      GDF-15, high sensitivity troponin T (hsTNT), and N-terminal prohormone of B-type
      natriuretic peptide (NTproBNP). RESULTS: There were 258 patients (21.9 %) with
      AKI (AKI stage 1 (AKI-1), n = 175 (14.9 %); AKI-2, n = 6 (0.5 %); AKI-3, n = 77
      (6.5 %)). The incidence of AKI-1 and AKI-3 increased significantly from the
      lowest to the highest tertiles of GDF-15. In logistic regression, preoperative
      GDF-15, additive Euroscore, age, plasma creatinine, diabetes mellitus, and
      duration of cardiopulmonary bypass were independently associated with AKI.
      Inclusion of GDF-15 in a logistic regression model comprising these variables
      significantly increased the area under the curve (AUC 0.738 without and 0.750
      with GDF-15 included) and the net reclassification ability to predict AKI.
      Comparably, in receiver operating characteristic analysis the predictive capacity
      of the CC-ARF score (AUC 0.628) was improved by adding GDF-15 (AUC 0.684) but
      this score also had lower predictability than the logistic regression model. In
      random forest analyses the predictive capacity of GDF-15 was especially
      pronounced in patients with normal plasma creatinine. CONCLUSION: This suggests
      that preoperative plasma GDF-15 independently predicts postoperative AKI in
      patients undergoing elective cardiac surgery and is particularly helpful for risk
      stratification in patients with normal creatinine. TRIAL REGISTRATION:
      NCT01166360 on July 20, 2010.

PMID- 27717385
TI  - L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine
      design and diagnosis.
AB  - BACKGROUND: Cervical cancer is associated with infection by certain subtypes of
      human papillomavirus (HPV). The L1 protein comprising HPV vaccine formulations
      elicits high-titre neutralizing antibodies and confers protection against
      specific HPV subtypes. HPV L2 protein is an attractive candidate for cross
      protective vaccines. HPV-33 and HPV-58 are very prevalent among Chinese women.
      METHODS: To study the gene intratypic variations and polymorphisms of HPV-33 and
      HPV-58 L1/L2 in Sichuan China, HPV-33 and HPV-58 L1 and L2 genes were sequenced
      and compared with other genes submitted to GenBank. Phylogenetic trees were
      constructed by maximum-likelihood and the Kimura 2-parameters methods (MEGA 6).
      The secondary structure was analyzed by PSIPred software, and HPV-33 and HPV-58
      L1 homology models were created by SWISS-MODEL software. The selection pressures
      acting on the L1/L2 genes were estimated by PAML 4.8. RESULTS: Among 124 HPV-33
      L1 sequences 20 single nucleotide mutations were observed included 8/20 non
      synonymous and 12/20 synonymous mutations. The 101 HPV-33 L2 sequences included
      12 single nucleotide mutations comprising 7/12 non-synonymous and 5/12 synonymous
      mutations. The 223 HPV-58 L1 sequences included 32 single nucleotide mutations
      comprising 9/32 non-synonymous and 23/32 synonymous mutations. The 201 HPV-58 L2
      sequences comprised 26 single nucleotide mutations including 9/26 non-synonymous
      and 17/26 synonymous mutations. Selective pressure analysis showed that most of
      the common non-synonymous mutations showed a positive selection. HPV-33 and HPV
      58 L2 were more stable than HPV-33 and HPV-58 L1. CONCLUSIONS: HPV-33 and HPV-58
      L2 were better candidates as clinical diagnostic targets compared with HPV-33 and
      HPV-58 L1. Clinical diagnostic probes and second-generation polyvalent vaccines
      should be designed on the basis of the unique sequence of HPV-33 and 58 L1/L2
      variations in Sichuan, to improve the accuracy of clinical detection and the
      protective efficiency of vaccines.

PMID- 27717386
TI  - Metabolic engineering of Corynebacterium glutamicum for enhanced production of 5
      aminovaleric acid.
AB  - BACKGROUND: 5-Aminovaleric acid (5AVA) is an important five-carbon platform
      chemical that can be used for the synthesis of polymers and other chemicals of
      industrial interest. Enzymatic conversion of L-lysine to 5AVA has been achieved
      by employing lysine 2-monooxygenase encoded by the davB gene and 5
      aminovaleramidase encoded by the davA gene. Additionally, a recombinant
      Escherichia coli strain expressing the davB and davA genes has been developed for
      bioconversion of L-lysine to 5AVA. To use glucose and xylose derived from
      lignocellulosic biomass as substrates, rather than L-lysine as a substrate, we
      previously examined direct fermentative production of 5AVA from glucose by
      metabolically engineered E. coli strains. However, the yield and productivity of
      5AVA achieved by recombinant E. coli strains remain very low. Thus,
      Corynebacterium glutamicum, a highly efficient L-lysine producing microorganism,
      should be useful in the development of direct fermentative production of 5AVA
      using L-lysine as a precursor for 5AVA. Here, we report the development of
      metabolically engineered C. glutamicum strains for enhanced fermentative
      production of 5AVA from glucose. RESULTS: Various expression vectors containing
      different promoters and origins of replication were examined for optimal
      expression of Pseudomonas putida davB and davA genes encoding lysine 2
      monooxygenase and delta-aminovaleramidase, respectively. Among them, expression
      of the C. glutamicum codon-optimized davA gene fused with His6-Tag at its N
      Terminal and the davB gene as an operon under a strong synthetic H36 promoter
      (plasmid p36davAB3) in C. glutamicum enabled the most efficient production of
      5AVA. Flask culture and fed-batch culture of this strain produced 6.9 and 19.7
      g/L (together with 11.9 g/L glutaric acid as major byproduct) of 5AVA,
      respectively. Homology modeling suggested that endogenous gamma-aminobutyrate
      aminotransferase encoded by the gabT gene might be responsible for the conversion
      of 5AVA to glutaric acid in recombinant C. glutamicum. Fed-batch culture of a C.
      glutamicum gabT mutant-harboring p36davAB3 produced 33.1 g/L 5AVA with much
      reduced (2.0 g/L) production of glutaric acid. CONCLUSIONS: Corynebacterium
      glutamicum was successfully engineered to produce 5AVA from glucose by optimizing
      the expression of two key enzymes, lysine 2-monooxygenase and delta
      aminovaleramidase. In addition, production of glutaric acid, a major byproduct,
      was significantly reduced by employing C. glutamicum gabT mutant as a host
      strain. The metabolically engineered C. glutamicum strains developed in this
      study should be useful for enhanced fermentative production of the novel C5
      platform chemical 5AVA from renewable resources.

PMID- 27717387
TI  - The associations between sedentary behaviour and mental health among adolescents:
      a systematic review.
AB  - BACKGROUND: With technological developments and modernised sedentary lifestyles
      has come an increase in diseases associated with inactivity such as obesity and
      other non-communicable diseases. Emerging evidence suggests that time spent
      sedentary may also interact with mental health. This systematic review examined
      the associations between sedentary behaviour and mental health problems among
      adolescents. METHODS: This systematic review followed Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses, and applied a quality assessment tool
      for quantitative studies to identity best available evidence. Following stringent
      search strategy of the databases; Cumulative Index to Nursing and Allied Health
      Literature, Global Health, Health Source: Nursing and Academic Edition, MEDLINE,
      PsychARTICLES and PsycINFO, we identified 32 articles eligible for review.
      RESULTS: All studies reported leisure screen time among adolescents, and two
      thirds of identified studies examined depressive symptomatology. Other mental
      health measures were; anxiety symptoms, self-esteem, suicide ideation,
      loneliness, stress, and psychological distress. Strong consistent evidence was
      found for the relationship between both depressive symptomatology and
      psychological distress, and time spent using screens for leisure. Moderate
      evidence supported the relationship between low self-esteem and screen use.
      Poorer mental health status was found among adolescents using screen time more
      than 2-3 h per day, and gender differences exist. Essential information was
      missing for quality of evidence including heterogeneity in mental health and
      screen time-based measures, and self-report data collection methods. CONCLUSIONS:
      The findings are of particular significance given the global public health
      concern of lifestyle-attributed diseases and the possibility for novel approaches
      to mental health. Future research should examine the psychological impact of
      reducing time spent using screens for leisure among adolescents, whilst
      accounting for possible confounding factors such as physical activity and dietary
      behaviours. It is critical that the reciprocal relationship between lifestyle
      behaviours and mental health is represented in both the psychiatric and public
      health forum.

PMID- 27717388
TI  - Performance-based incentives may be appropriate to address challenges to delivery
      of prevention of vertical transmission of HIV services in rural Mozambique: a
      qualitative investigation.
AB  - BACKGROUND: Performance-based incentives (PBIs) have garnered global attention as
      a promising strategy to improve healthcare delivery to vulnerable populations.
      However, literature gaps in the context in which an intervention is implemented
      and how the PBIs were developed exist. Therefore, we (1) characterized the
      barriers and promoters to prevention of vertical transmission of HIV (PVT)
      service delivery in rural Mozambique, where the vertical transmission rate is 12
      %, and (2) assessed the appropriateness for a PBI's intervention and application
      to PVT. METHODS: We conducted 24 semi-structured interviews with nurses,
      volunteers, community health workers, and traditional birth attendants about the
      barriers and promoters they experienced delivering PVT services. We then explored
      emergent themes in subsequent focus group discussions (n = 7, total participants
      N = 92) and elicited participant perspectives on PBIs. The ecological motivation
      opportunity-ability framework guided our iterative data collection and thematic
      analysis processes. RESULTS: The interviews revealed that while all health worker
      cadres were motivated intrinsically and by social recognition, they were
      dissatisfied with low and late remuneration. Facility-based staff were challenged
      by factors across the rest of the ecological levels, primarily in the opportunity
      domain, including the following: poor referral and record systems (work mandate),
      high workload, stock-outs, poor infrastructure (facility environment), and delays
      in obtaining patient results and donor payment discrepancies (administrative).
      Community-based cadres' opportunity challenges included lack of supplies,
      distance (work environment), lack of incorporation into the health system
      (administration), and ability challenges of incorrect knowledge (health worker).
      PBIs based on social recognition and that enable action on intrinsic motivation
      through training, supervision, and collaboration were thought to have the most
      potential for targeting improvements in record and referral systems and better
      integrating community-based health workers into the health system. Concerns about
      the implementation of incentives included neglect of non-incentivized tasks and
      distorted motivation among colleagues. CONCLUSIONS: We found that highly
      motivated health workers encountered severe opportunity challenges in their PVT
      mandate. PBIs have the potential to address key barriers that facility- and
      community-based health workers encounter when delivering PVT services,
      specifically by building upon existing intrinsic motivation and leveraging highly
      valued social recognition. We recommend a controlled intervention to monitor
      incentives' effects on worker motivation and non-incentivized tasks to generate
      insights about the feasibility of PBIs to improve the delivery of PVT services.

PMID- 27717389
TI  - "That's enough patients for everyone!": Local stakeholders' views on attracting
      patients into Barbados and Guatemala's emerging medical tourism sectors.
AB  - BACKGROUND: Medical tourism has attracted considerable interest within the Latin
      American and Caribbean (LAC) region. Governments in the region tout the economic
      potential of treating foreign patients while several new private hospitals
      primarily target international patients. This analysis explores the perspectives
      of a range of medical tourism sector stakeholders in two LAC countries, Guatemala
      and Barbados, which are beginning to develop their medical tourism sectors. These
      perspectives provide insights into how beliefs about international patients are
      shaping the expanding regional interest in medical tourism. METHODS: Structured
      around the comparative case study methodology, semi-structured interviews were
      conducted with 50 medical tourism stakeholders in each of Guatemala and Barbados
      (n = 100). To capture a comprehensive range of perspectives, stakeholders were
      recruited to represent civil society (n = 5/country), health human resources (n =
      15/country), public health care and tourism sectors (n = 15/country), and private
      health care and tourism sectors (n = 15/country). Interviews were transcribed
      verbatim, coded using a collaborative process of scheme development, and analyzed
      thematically following an iterative process of data review. RESULTS: Many
      Guatemalan stakeholders identified the Guatemalan-American diaspora as a
      significant source of existing international patients. Similarly, Barbadian
      participants identified their large recreational tourism sector as creating a
      ready source of foreign patients with existing ties to the country. While both
      Barbadian and Guatemalan medical tourism proponents share a common understanding
      that intra-regional patients are an existing supply of international patients
      that should be further developed, the dominant perception driving interest in
      medical tourism is the proximity of the American health care market. In the short
      term, this supplies a vision of a large number of Americans lacking adequate
      health insurance willing to travel for care, while in the long term, the
      Affordable Care Act is seen to be an enormous potential driver of future medical
      tourism as it is believed that private insurers will seek to control costs by
      outsourcing care to providers abroad. CONCLUSIONS: Each country has some
      comparative advantage in medical tourism. Assumptions about a large North
      American patient base, however, are not supported by reliable evidence. Pursuing
      this market could incur costs borne by patients in their public health systems.

PMID- 27717390
TI  - Perip7lakin is a target for autoimmunity in asthma.
AB  - The role of autoimmunity targeting epithelial antigens in asthma has been
      suggested, in particular in non-atopic and severe asthma. Periplakin, a
      desmosomal component, is involved in epithelial cohesion and intracellular
      signaling. We detected anti-periplakin IgG antibodies in 47/260 (18 %) patients
      with asthma, with no association with severity or atopy. In addition, anti
      periplakin IgE antibodies were detected in 12 of 138 tested patients (8.7 %) and
      were more frequently observed in patients with than without nasal polyposis. This
      study identifies a new autoimmune epithelial target in asthma. Whether periplakin
      autoimmunity (both IgG and IgE auto-antibodies) is involved in asthma
      pathogenesis remains to be studied during the disease course of these patients.

PMID- 27717392
TI  - Risk of selection bias in randomized trials: further insight.
AB  - The quality of randomization is an under-appreciated facet of trial design. The
      present piece represents an advance in our collective understanding of how
      allocation concealment and randomization relate to risk of selection bias in
      randomized trials, and other measures are also considered. Though the
      overwhelming majority of the advice given is timely and correct, it is more
      instructive to focus on the relatively narrow sliver of advice that is incorrect
      (namely, that trials should not stratify by site, and that unrestricted
      randomization is a solution to the problem of selection bias), so it is in this
      context that the comments here must be understood. In no way is this intended to
      be a rebuttal of the excellent work we have before us. Rather, it is a
      refinement.

PMID- 27717391
TI  - The oral health of refugees and asylum seekers: a scoping review.
AB  - INTRODUCTION: Improving the oral health of refugees and asylum seekers is a
      global priority, yet little is known about the overall burden of oral diseases
      and their causes for this population. OBJECTIVE: To synthesize available evidence
      on the oral health of, and access to oral health care by this population.
      METHODS: Using a scoping review methodology, we retrieved 3321 records from eight
      databases and grey literature; 44 publications met the following inclusion
      criteria: empirical research focused on refugees and/or asylum seekers' oral
      health, published between 1990 and 2014 in English, French, Italian, Portuguese,
      or Spanish. Analysis included descriptive and thematic analysis, as well as
      critical appraisal using the Critical Appraisal Skills Programme (CASP) criteria
      for quantitative and qualitative studies. RESULTS: The majority of publications
      (86 %) were from industrialized countries, while the majority of refugees are
      resettled in developing countries. The most common study designs were
      quantitative (75 %). Overall, the majority of studies (76 %) were of good
      quality. Studies mainly explored oral health status, knowledge and practices; a
      minority (9 %) included interventions. The refugee populations in the studies
      showed higher burden of oral diseases and limited access to oral health care
      compared to even the least privileged populations in the host countries. Minimal
      strategies to improve oral health have been implemented; however, some have
      impressive outcomes. CONCLUSIONS: Oral health disparities for this population
      remain a major concern. More research is needed on refugees in developing
      countries, refugees residing in refugee camps, and interventions to bridge oral
      health disparities. This review has utility for policymakers, practitioners,
      researchers, and other stakeholders working to improve the oral health of this
      population.

PMID- 27717393
TI  - Effectiveness of a multicomponent intervention to enhance implementation of a
      healthy canteen policy in Australian primary schools: a randomised controlled
      trial.
AB  - BACKGROUND: The implementation of school nutrition policies, which govern the
      provision of food in schools, is recommended as a public health strategy to
      support the development of healthy dietary behaviours in school-aged children.
      Despite this, research internationally and in Australia indicates that few
      schools implement such policies. This study aims to examine whether a
      theoretically designed, multi-strategy intervention was effective in increasing
      the implementation of a healthy canteen policy in Australian primary schools.
      METHODS: A parallel group randomised controlled trial was conducted with all
      government and Catholic primary schools within one region in New South Wales,
      Australia who had an operational canteen that provided food to primary school
      aged children (5-12 years) and were not currently receiving an intervention to
      change their canteen practices. Schools randomised to the intervention arm
      received a 9-month multicomponent intervention including ongoing support,
      provision of resources, performance monitoring and feedback, executive support
      and recognition. The primary outcomes were the proportion of the schools with a
      canteen menu that: i) did not include 'red' or 'banned' items according to the
      healthy canteen policy; and ii) had more than 50 % 'green' items. The primary
      outcome was assessed via menu audit at baseline and follow up by dietitians
      blinded to group allocation. RESULTS: Fifty-three eligible schools were
      randomised to either the intervention or control group (28 intervention; 25
      control). Analyses with 51 schools who returned school menus found that
      intervention schools were significantly more likely relative to control schools
      to have a menu without 'red' or 'banned' items (RR = 5.78 (1.45-23.05); p =
      0.002) and have at least 50 % of menu items classified as green (RR = 2.03 (1.01
      4.08); p = 0.03). CONCLUSIONS: This study found that a multi-component
      intervention was effective in improving primary schools' compliance with a
      healthy canteen policy. Given the lack of evidence regarding how best to support
      schools with implementing evidence-based policies to improve child diet, this
      trial for the first time provides high quality evidence to practitioners and
      policy makers seeking to improve nutrition policy implementation in schools.
      TRIAL REGISTRATION: This trial was prospectively registered with the Australian
      New Zealand Clinical Trials Registry ( ACTRN12614001148662 ) 30th October 2014.

PMID- 27717394
TI  - Musculoskeletal care pathways for adults with hip and knee pain at the interface
      between primary and secondary care: protocol for a systematic review.
AB  - BACKGROUND: Musculoskeletal (MSK) conditions are the most frequently reported
      chronic conditions and one of the biggest causes of disability in the UK. Given
      the ageing population and the impact of these problems, the demand for MSK
      treatment will rise. Despite reduced waiting times, MSK pathways have remained
      variable and inconsistent and need to be improved to meet patient needs. The aim
      of this systematic review is to understand the evidence for the effectiveness of
      current models of service delivery and care pathways for adult hip/knee pain
      patients accessing secondary care for specialist opinions. METHODS: MEDLINE,
      MEDLINE In-Process, CINAHL, Embase, PEDro, PubMed, Web of Science, Cochrane
      Central and HMIC databases will be searched without language restrictions for
      papers published from 1990 onward. Websites will be reviewed for grey literature
      including care pathways, policy documents and unpublished MSK research.
      Additionally, reference lists will be checked and citations tracked for included
      studies. DISCUSSION: The following evidence will be included: research
      considering care pathways at the intersection between primary and secondary care
      for adults with hip and/or knee pain in countries with an established clinical
      pathway. Studies considering generalised inflammatory arthropathy and post
      surgical care pathways will be excluded. Screening for included data will be
      conducted independently by two reviewers. After benchmarking, quality assessment
      and data extraction will be conducted by one reviewer and checked by a second. A
      mixed method analysis will be conducted. This systematic review will be used as
      part of a programme of research to identify best practice for MSK hip and knee
      pain care pathways. It will provide recommendations for pathway re-design to meet
      patient needs and ensure efficient streamlining of the patient journey. The
      review will combine a wide range of information sources including patient and
      clinician opinion, clinical guidelines, health service delivery research and
      stakeholder requirements. This should result in a pathway that provides better
      patient experience and outcomes, whilst meeting the demands placed on the NHS for
      high-quality evidence-based interventions with efficient use of resources.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016035510.

PMID- 27717395
TI  - Wild and native plants and mushrooms sold in the open-air markets of south
      eastern Poland.
AB  - BACKGROUND: The study of plants and fungi sold in open-air markets is an
      important part of ethnobotanical enquiry. Only few such studies were carried out
      in Europe. METHODS: Four of the largest open-air markets of south-eastern Poland
      were visited regularly, and the plants sold in them were recorded between 2013
      and 2015. The aim of the study was to record native and/or wild species sold in
      the markets. All the plants sold in the markets were photographed regularly. In
      each market, 25 sellers were interviewed. Voucher specimens were collected and
      fungi were identified using DNA barcoding. RESULTS: Altogether, 468 species of
      plants were recorded, 117 of them native to south-eastern Poland - 19 only
      collected from the wild and 11 both wild and cultivated. Seventeen of the species
      are under legal protection. Most protected plants were sold from cultivation,
      although proper authorization procedures had not been performed. Thirty-two
      species of fungi were sold (including two cultivated species), all of them for
      culinary purposes. Two species (Lactarius quieticolor, Leccinum schistophilum)
      are new to the mycobiota of Poland. Ornamental plants constituted a large section
      of the market, and they dominated the group of native species. Food plants
      dominated among wild-collected plants and were sold mainly as fruits for jams,
      juices and alcoholic drinks, or as culinary herbs. Very few medicinal or green
      vegetable plants were sold. An interesting feature of the markets was the sale of
      Ledum palustre as an insect repellent. CONCLUSIONS: Finding two species of fungi
      which are new to Poland highlights the importance of DNA barcoding in
      ethnomycological studies. Most items in the markets are ornamental plants, or
      edible fruits and mushrooms. Very few medicinal plants and green vegetables are
      sold, which differentiates the markets from southern European ones. Such a
      pattern is probably the model for most central European markets.

PMID- 27717396
TI  - Viable phenotype of ILNEB syndrome without nephrotic impairment in siblings
      heterozygous for unreported integrin alpha3 mutations.
AB  - BACKGROUND: Integrin alpha3 (ITGA3) gene mutations are associated with
      Interstitial Lung disease, Nephrotic syndrome and Epidermolysis bullosa (ILNEB
      syndrome). To date only six patients are reported: all carried homozygous ITGA3
      mutations and presented a dramatically severe phenotype leading to death before
      age 2 years, from multi-organ failure due to interstitial lung disease and
      congenital nephrotic syndrome. The involvement of skin and cutaneous adnexa was
      variable with sparse hair and nail dysplasia combined or not to skin lesions
      ranging from skin fragility to epidermolysis bullosa-like blistering. RESULTS: We
      report on two siblings of 13 and 9 years born to non-consanguineous healthy
      parents, who display growth delay, severe pulmonary fibrosis with fatigue,
      dyspnea on exertion and wheezing, atrophic skin with erythematosus lesions, rare
      eyelashes/eyebrows and pachyonychia. By exome sequencing, we identified two
      unreported ITGA3 missense mutations, c.373G>A (p.(G125R)) in exon 3 and c.821G>A
      (p.(R274Q)) in exon 6, affecting highly conserved residues in the integrin alpha3
      extracellular N-terminal beta-propeller domain. Homology modelling of alpha3beta1
      heterodimer fragment, encompassing the mutation sites, showed that G125 plays a
      pivotal structural role in the beta-propeller, while R274 might prevent the
      interaction between integrin and urokinase complex. CONCLUSION: We report a
      variant of ILNEB syndrome in two siblings differing from the previously reported
      patients in the lack of nephrotic impairment and survival beyond childhood. Our
      siblings are the first reported compound heterozygous for ITGA3 mutations; this
      state as well as the hypomorphic nature of their p.(R274Q) mutation likely
      account for their survival.

PMID- 27717397
TI  - Prediction of gestational age based on genome-wide differentially methylated
      regions.
AB  - BACKGROUND: We explored the association between gestational age and cord blood
      DNA methylation at birth and whether DNA methylation could be effective in
      predicting gestational age due to limitations with the presently used methods. We
      used data from the Norwegian Mother and Child Birth Cohort study (MoBa) with
      Illumina HumanMethylation450 data measured for 1753 newborns in two batches: MoBa
      1, n = 1068; and MoBa 2, n = 685. Gestational age was computed using both
      ultrasound and the last menstrual period. We evaluated associations between DNA
      methylation and gestational age and developed a statistical model for predicting
      gestational age using MoBa 1 for training and MoBa 2 for predictions. The
      prediction model was additionally used to compare ultrasound and last menstrual
      period-based gestational age predictions. Furthermore, both CpGs and associated
      genes detected in the training models were compared to those detected in a
      published prediction model for chronological age. RESULTS: There were 5474 CpGs
      associated with ultrasound gestational age after adjustment for a set of
      covariates, including estimated cell type proportions, and Bonferroni-correction
      for multiple testing. Our model predicted ultrasound gestational age more
      accurately than it predicted last menstrual period gestational age. CONCLUSIONS:
      DNA methylation at birth appears to be a good predictor of gestational age.
      Ultrasound gestational age is more strongly associated with methylation than last
      menstrual period gestational age. The CpGs linked with our gestational age
      prediction model, and their associated genes, differed substantially from the
      corresponding CpGs and genes associated with a chronological age prediction
      model.

PMID- 27717398
TI  - Rapid change of fecal microbiome and disappearance of Clostridium difficile in a
      colonized infant after transition from breast milk to cow milk.
AB  - BACKGROUND: Clostridium difficile is the most common known cause of antibiotic
      associated diarrhea. Upon the disturbance of gut microbiota by antibiotics, C.
      difficile establishes growth and releases toxins A and B, which cause tissue
      damage in the host. The symptoms of C. difficile infection disease range from
      mild diarrhea to pseudomembranous colitis and toxic megacolon. Interestingly, 10
      50 % of infants are asymptomatic carriers of C. difficile. This longitudinal
      study of the C. difficile colonization in an infant revealed the dynamics of C.
      difficile presence in gut microbiota. METHODS: Fifty fecal samples, collected
      weekly between 5.5 and 17 months of age from a female infant who was an
      asymptomatic carrier of C. difficile, were analyzed by 16S rRNA gene sequencing.
      RESULTS: Colonization switching between toxigenic and non-toxigenic C. difficile
      strains as well as more than 100,000-fold fluctuations of C. difficile counts
      were observed. C. difficile toxins were detected during the testing period in
      some infant stool samples, but the infant never had diarrhea. Although fecal
      microbiota was stable during breast feeding, a dramatic and permanent change of
      microbiota composition was observed within 5 days of the transition from human
      milk to cow milk. A rapid decline and eventual disappearance of C. difficile
      coincided with weaning at 12.5 months. An increase in the relative abundance of
      Bacteroides spp., Blautia spp., Parabacteroides spp., Coprococcus spp.,
      Ruminococcus spp., and Oscillospira spp. and a decrease of Bifidobacterium spp.,
      Lactobacillus spp., Escherichia spp., and Clostridium spp. were observed during
      weaning. The change in microbiome composition was accompanied by a gradual
      increase of fecal pH from 5.5 to 7. CONCLUSIONS: The bacterial groups that are
      less abundant in early infancy, and that increase in relative abundance after
      weaning, likely are responsible for the expulsion of C. difficile.

PMID- 27717400
TI  - Expression and regulation of ATF6alpha in the mouse uterus during embryo
      implantation.
AB  - BACKGROUND: ATF6alpha, one of the sensor proteins in the stress signaling pathway
      of the endoplasmic reticulum, is located in the membrane of the endoplasmic
      reticulum. To date, the physiological function of ATF6alpha in the process of
      embryo implantation has not been reported. METHODS: In this study, the expression
      pattern of ATF6alpha in the mouse uterus during peri-implantation and the estrous
      cycle was detected by real-time PCR, western blot and immunohistochemistry.
      RESULTS: ATF6alpha mRNA and protein levels were higher in the uterus near the
      implantation site on day 5 and were intensely expressed in the secondary decidual
      zone (SDZ) on days 7-8. In the uteri of pseudopregnant mice, ATF6alpha mRNA and
      protein levels were lower on day 5 than on other days. The activating blastocyst
      and artificial decidualization had an obvious effect of increasing the expression
      of ATF6alpha. In addition, the expression of ATF6alpha was affected by
      progesterone (P4) and estrogen (E2) in ovariectomized mice. This finding is
      further supported by evidence from mice during the estrous cycle. CONCLUSIONS:
      Thus, we have concluded that ATF6alpha may play an important role during embryo
      implantation and decidualization.

PMID- 27717403
TI  - The early bird catches the term: combining twitter and news data for event
      detection and situational awareness.
AB  - BACKGROUND: Twitter updates now represent an enormous stream of information
      originating from a wide variety of formal and informal sources, much of which is
      relevant to real-world events. They can therefore be highly useful for event
      detection and situational awareness applications. RESULTS: In this paper we apply
      customised filtering techniques to existing bio-surveillance algorithms to detect
      localised spikes in Twitter activity, showing that these correspond to real
      events with a high level of confidence. We then develop a methodology to
      automatically summarise these events, both by providing the tweets which best
      describe the event and by linking to highly relevant news articles. This news
      linkage is accomplished by identifying terms occurring more frequently in the
      event tweets than in a baseline of activity for the area concerned, and using
      these to search for news. We apply our methods to outbreaks of illness and events
      strongly affecting sentiment and are able to detect events verifiable by third
      party sources and produce high quality summaries. CONCLUSIONS: This study
      demonstrates linking event detection from Twitter with relevant online news to
      provide situational awareness. This builds on the existing studies that focus on
      Twitter alone, showing that integrating information from multiple online sources
      can produce useful analysis.

PMID- 27717401
TI  - Adoptive transfer of M2 macrophages reduces neuropathic pain via opioid peptides.
AB  - BACKGROUND: During the inflammation which occurs following nerve damage,
      macrophages are recruited to the site of injury. Phenotypic diversity is a
      hallmark of the macrophage lineage and includes pro-inflammatory M1 and anti
      inflammatory M2 populations. Our aim in this study was to investigate the ability
      of polarized M0, M1, and M2 macrophages to secrete opioid peptides and to examine
      their relative contribution to the modulation of neuropathic pain. METHODS: Mouse
      bone marrow-derived cells were cultured as unstimulated M0 macrophages or were
      stimulated into an M1 phenotype using lipopolysaccharide and interferon-gamma or
      into an M2 phenotype using interleukin-4. The macrophage phenotypes were verified
      using flow cytometry for surface marker analysis and cytokine bead array for
      cytokine profile assessment. Opioid peptide levels were measured by
      radioimmunoassay and enzyme immunoassay. As a model of neuropathic pain, a
      chronic constriction injury (CCI) of the sciatic nerve was employed. Polarized
      M0, M1, and M2 macrophages (5 * 105 cells) were injected perineurally twice, on
      days 14 and 15 following CCI or sham surgery. Mechanical and heat sensitivity
      were measured using the von Frey and Hargreaves tests, respectively. To track the
      injected macrophages, we also transferred fluorescently stained polarized cells
      and analyzed the surface marker profile of endogenous and injected cells in the
      nerves ex vivo. RESULTS: Compared to M0 and M1 cells, M2 macrophages contained
      and released higher amounts of opioid peptides, including Met-enkephalin,
      dynorphin A (1-17), and beta-endorphin. M2 cells transferred perineurally at the
      nerve injury site reduced mechanical, but not heat hypersensitivity following the
      second injection. The analgesic effect was reversed by the perineurally applied
      opioid receptor antagonist naloxone methiodide. M2 cells did not affect
      sensitivity following sham surgery. Neither M0 nor M1 cells altered mechanical
      and heat sensitivity in CCI or sham-operated animals. Tracing the fluorescently
      labeled M0, M1, and M2 cells ex vivo showed that they remained in the nerve and
      preserved their phenotype. CONCLUSIONS: Perineural transplantation of M2
      macrophages resulted in opioid-mediated amelioration of neuropathy-induced
      mechanical hypersensitivity, while M1 macrophages did not exacerbate pain.
      Therefore, rather than focusing on macrophage-induced pain generation, promoting
      opioid-mediated M2 actions may be more relevant for pain control.

PMID- 27717402
TI  - Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus
      effector differentiation.
AB  - BACKGROUND: In malaria-endemic areas, the first exposure to malaria antigens
      often occurs in utero when the fetal immune system is poised towards the
      development of tolerance. Children exposed to placental malaria have an increased
      risk of clinical malaria in the first few years of life compared to unexposed
      children. Recent work has suggested the potential of pregnancy-associated malaria
      to induce immune tolerance in children living in malaria-endemic areas. A study
      was completed to evaluate the effect of malaria exposure during pregnancy on
      fetal immune tolerance and effector responses. METHODS: Using cord blood samples
      from a cohort of mother-infant pairs followed from early in pregnancy until
      delivery, flow cytometry analysis was completed to assess the relationship
      between pregnancy-associated malaria and fetal cord blood CD4 and dendritic cell
      phenotypes. RESULTS: Cord blood FoxP3+ Treg counts were higher in infants born to
      mothers with Plasmodium parasitaemia early in pregnancy (12-20 weeks of
      gestation; p = 0.048), but there was no association between Treg counts and the
      presence of parasites in the placenta at the time of delivery (by loop-mediated
      isothermal amplification (LAMP); p = 0.810). In contrast, higher frequencies of
      activated CD4 T cells (CD25+FoxP3-CD127+) were observed in the cord blood of
      neonates with active placental Plasmodium infection at the time of delivery (p =
      0.035). This population exhibited evidence of effector memory differentiation,
      suggesting priming of effector T cells in utero. Lastly, myeloid dendritic cells
      were higher in the cord blood of infants with histopathologic evidence of
      placental malaria (p < 0.0001). CONCLUSION: Together, these data indicate that in
      utero exposure to malaria drives expansion of both regulatory and effector T
      cells in the fetus, and that the timing of this exposure has a pivotal role in
      determining the polarization of the fetal immune response.

PMID- 27717399
TI  - An epigenetic clock for gestational age at birth based on blood methylation data.
AB  - BACKGROUND: Gestational age is often used as a proxy for developmental maturity
      by clinicians and researchers alike. DNA methylation has previously been shown to
      be associated with age and has been used to accurately estimate chronological age
      in children and adults. In the current study, we examine whether DNA methylation
      in cord blood can be used to estimate gestational age at birth. RESULTS: We find
      that gestational age can be accurately estimated from DNA methylation of neonatal
      cord blood and blood spot samples. We calculate a DNA methylation gestational age
      using 148 CpG sites selected through elastic net regression in six training
      datasets. We evaluate predictive accuracy in nine testing datasets and find that
      the accuracy of the DNA methylation gestational age is consistent with that of
      gestational age estimates based on established methods, such as ultrasound. We
      also find that an increased DNA methylation gestational age relative to clinical
      gestational age is associated with birthweight independent of gestational age,
      sex, and ancestry. CONCLUSIONS: DNA methylation can be used to accurately
      estimate gestational age at or near birth and may provide additional information
      relevant to developmental stage. Further studies of this predictor are warranted
      to determine its utility in clinical settings and for research purposes. When
      clinical estimates are available this measure may increase accuracy in the
      testing of hypotheses related to developmental age and other early life
      circumstances.

PMID- 27717404
TI  - Composition and cytotoxic and antioxidant activities of the oil of Piper aequale
      Vahl.
AB  - BACKGROUND: Piper aequale Vahl is a small shrub that grows in the shadow of large
      trees in the Carajas National Forest, Municipality of Parauapebas, Para state,
      Brazil. The local people have used the plant against rheumatism and inflammation.
      METHODS: The essential oil of the aerial parts was extracted and analyzed by GC
      and GC-MS. The MTT colorimetric assay was used to measuring the cytotoxic
      activity of the oil against human cancer lines. The determination of antioxidant
      activity of the oil was conducted by DPPH radical scavenging assay. RESULTS: The
      main constituents were delta-elemene (18.92 %), beta-pinene (15.56 %), alpha
      pinene (12.57 %), cubebol (7.20 %), beta-atlantol (5.87 %), and bicyclogermacrene
      (5.51 %), totalizing 65.63 % of the oil. The oil displayed a strong in vitro
      cytotoxic activity against the human cancer cell lines HCT-116 (colon) and ACP03
      (gastric) with IC50values of 8.69 MUg/ml and 1.54 MUg/ml, respectively. The oil
      has induced the apoptosis in a gastric cancer cells in all tested concentration
      (0.75-3.0 MUg/ml), after 72 h of treatment, when compared to negative control (p
      < 0.001). Also, the oil showed a significant antioxidant activity (280.9 +/- 22.2
      mg TE/ml), when analyzed as Trolox equivalent, and a weak acetylcholinesterase
      inhibition, with a detection limit of 100 ng, when compared to the physostigmine
      standard (1.0 ng). CONCLUSION: The higher cell growth inhibition induced by the
      oil of P. aequale is probably due to its primary terpene compounds, which were
      previously reported in the proliferation inhibition, in stimulation of apoptosis
      and induction of cell cycle arrest in malignant cells.

PMID- 27717405
TI  - Group schema therapy versus group cognitive behavioral therapy for social anxiety
      disorder with comorbid avoidant personality disorder: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Social anxiety disorder (SAD) with comorbid avoidant personality
      disorder (APD) has a high prevalence and is associated with serious psychosocial
      problems and high societal costs. When patients suffer from both SAD and APD, the
      Dutch multidisciplinary guidelines for personality disorders advise offering
      prolonged cognitive behavioral therapy (CBT). Recently there is increasing
      evidence for the effectiveness of schema therapy (ST) for personality disorders
      such as borderline personality disorder and cluster C personality disorders.
      Since ST addresses underlying personality characteristics and maladaptive coping
      strategies developed in childhood, this treatment might be particularly effective
      for patients with SAD and comorbid APD. To our knowledge, there are no studies
      comparing CBT with ST in this particular group of patients. This superiority
      trial aims at comparing the effectiveness of these treatments. As an additional
      goal, predictors and underlying mechanisms of change will be explored.
      METHODS/DESIGN: The design of the study is a multicentre two-group randomized
      controlled trial (RCT) in which the treatment effect of group cognitive
      behavioral therapy (GCBT) will be compared to that of group schema therapy (GST)
      in a semi-open group format. A total of 128 patients aged 18-65 years old will be
      enrolled. Patients will receive 30 sessions of GCBT or GST during a period of
      approximately 9 months. Primary outcome measures are the Liebowitz Social Anxiety
      Scale Self-Report (LSAS-SR) for social anxiety disorder and the newly developed
      Avoidant Personality Disorder Severity Index (AVPDSI) for avoidant personality
      disorder. Secondary outcome measures are the MINI section SAD, the SCID-II
      section APD, the Schema Mode Inventory (SMI-2), the Inventory of Depressive
      Symptomatology Self-Report (IDS-SR), the World Health Organization Quality of
      Life-BREF (WHOQOL-BREF), the Difficulties in Emotion Regulation Scale (DERS), the
      Rosenberg Self-Esteem Scale (RSES) and the Acceptance and Action Questionnaire
      (AAQ-II). Data will be collected at the start, halfway and at the end of the
      treatment, followed by measurements at 3, 6 and 12 months post-treatment.
      DISCUSSION: The trial will increase our knowledge on the effectiveness and
      applicability of both treatment modalities for patients suffering from both
      diagnoses. TRIAL REGISTRATION: Dutch Trial Register: NTR3921 . Registered on 25
      March 2013.

PMID- 27717406
TI  - Mosquito-borne heartworm Dirofilaria immitis in dogs from Australia.
AB  - BACKGROUND: Heartworm (Dirofilaria immitis) in dogs is considered endemic in
      Australia, but the clinical heartworm disease caused by the heartworm is rare and
      prevalence is low. The mainstream prevention of the heartworm is based on
      macrocyclic lactone (ML) administration. The aim of this study was to confirm
      endemism of the heartworm under current Australian conditions using a cohort of
      recent microfilaria-positive dogs which were on variable heartworm prevention.
      METHODS: A hotspot of canine heartworm antigen-positive and microfilaria-positive
      dogs has been detected recently in Queensland, Australia. Blood samples from 39
      dogs from Queensland and two dogs from New South Wales were investigated for
      canine filarioids. Rapid antigen diagnostic tests capable of detection of D.
      immitis and real-time PCR for quantification and differentiation between D.
      immitis from Acanthocheilonema reconditum with quantification of microfilariae in
      canine blood samples, together with D. immitis specific real-time PCR assay, were
      applied to microfilaria-positive dogs. The P-glycoprotein genotype was determined
      to test whether Australian-sourced heartworm shared the same genetic markers as
      those suspected of ML-resistance in North America. RESULTS: Only D. immitis was
      detected in the samples from Queensland and New South Wales, Australia. Using
      high resolution melt real-time PCR and D. immitis specific real-time PCR, the
      calculated microfilaria concentration ranged from 1 to 44,957 microfilariae/ml
      and from 7 to 60,526 microfilariae/ml, respectively. DNA sequencing of the PCR
      products confirmed D. immitis. Fifteen of the examined dogs were on putative,
      rigorous ML prevention. For the remaining dogs, compliance with heartworm
      prevention was unknown or reported as inconsistent. Wild-type genotype AA-GG of
      the P-glycoprotein locus of D. immitis sequence has been obtained for three blood
      samples. Due to the incomplete history, any suggestion of a loss of efficacy of
      MLs must be treated as 'remotely possible'. In the immediate future, records of
      preventative administration and annual antigen testing would be required to
      determine any problems with the efficacy of preventatives. CONCLUSIONS: The
      prevalence of canine heartworm in Australia remains poorly understood. It is
      generally assumed to be low by veterinary practitioners. The localised increase
      in the study area confirms endemism of canine heartworm and a requirement for
      ongoing vigilance through annual heartworm testing to better understand the
      changing distribution of canine heartworm, client compliance, as well as to
      detect any change in ML-susceptibility.

PMID- 27717407
TI  - A feasibility study of the clinical effectiveness and cost-effectiveness of
      individual cognitive behavioral therapy for panic disorder in a Japanese clinical
      setting: an uncontrolled pilot study.
AB  - BACKGROUND: In Japan, cognitive behavioral therapy (CBT) for panic disorder (PD)
      is not well established. Therefore, a feasibility study of the clinical
      effectiveness and cost-effectiveness of CBT for PD in a Japanese clinical setting
      is urgently required. This was a pilot uncontrolled trial and the intervention
      consisted of a 16-week CBT program. The primary outcome was Panic Disorder
      Severity Scale (PDSS) scores. Quality of life was assessed using the EuroQol's EQ
      5D questionnaire. Assessments were conducted at baseline, 8 weeks, and at the end
      of the study. Fifteen subjects completed outcome measures at all assessment
      points. RESULTS: At post-CBT, the mean reduction in PDSS scores from baseline was
      -6.6 (95 % CI 3.80 to -9.40, p < 0.001) with a Cohen's d = 1.77 (95 % CI 0.88
      2.55). Ten (66.7 %) participants achieved a 40 % or greater reduction in PDSS. By
      calculating areas under the curve for EQ-5D index changes, we estimated that
      patients gained a minimum of 0.102 QALYs per 1 year due to the CBT. CONCLUSIONS:
      This study demonstrated that individual CBT for PD may be useful in Japanese
      clinical settings but further randomized control trials are needed. TRIAL
      REGISTRATION: UMIN-CTR UMIN000022693 (retrospectively registered).

PMID- 27717410
TI  - Metabolic effects of quail eggs in diabetes-induced rats: comparison with chicken
      eggs.
AB  - BACKGROUND: Quail eggs as a food item have recently been introduced into the diet
      of some Cameroonians. These eggs are being sold in local markets, but with many
      unfounded health claims. One claim is that quail eggs can reduce blood glucose
      levels in diabetics. It was therefore necessary to evaluate the effect of
      consuming quail eggs on blood glucose levels, lipid profiles, and oxidative
      stress parameters in diabetes-induced rats. METHODS: Twenty Wistar rats weighing,
      on average, 250 g were divided into four groups of five rats each. Group 1
      consisted of rats with normal blood glucose, and the other three groups (2, 3,
      and 4) consisted of diabetes-induced rats achieved by intravenous injection of
      streptozotocin. During 16 days, rats in groups 1 and 2 received distilled water;
      and rats in groups 3 and 4 received quail and chicken eggs, respectively, with
      gastroesophageal probe at a dose of 1 mL/200 g body weight. Fasting blood glucose
      levels were determined in all the groups on the 1st, 7th, 14th, and 17th days
      after induction of diabetes. On the 17th day, the fasting rats were sacrificed,
      and blood and liver samples were collected for biochemical analyses. RESULTS: In
      17 days, the consumption of quail and chicken eggs had no effect on blood glucose
      levels of diabetic rats. Total cholesterol levels were higher in groups 3 (75.59
      mg/dL) and 4 (59.41 mg/dL) compared to group 2 (55.67 mg/dl), although these
      differences were not significant (all p>0.05). Triglyceride levels were
      significantly higher (p<0.05) in groups 3 (106.52 mg/dL) and 4 (109.65 mg/dL)
      compared to group 2 (65.82 mg/dL). Quail eggs had no effect on oxidative stress
      parameters (malondialdehyde, hydroperoxides, and catalase). CONCLUSIONS: The
      consumption of quail eggs by diabetic rats at the tested dose had no effect on
      blood glucose level and oxidative stress parameters and may have a negative
      effect on lipid profile.

PMID- 27717408
TI  - The structure and diversity of human, animal and environmental resistomes.
AB  - BACKGROUND: Antibiotic resistance genes (ARGs) are widespread but cause problems
      only when present in pathogens. Environments where selection and transmission of
      antibiotic resistance frequently take place are likely to be characterized by
      high abundance and diversity of horizontally transferable ARGs. Large-scale
      quantitative data on ARGs is, however, lacking for most types of environments,
      including humans and animals, as is data on resistance genes to potential co
      selective agents, such as biocides and metals. This paucity prevents efficient
      identification of risk environments. RESULTS: We provide a comprehensive
      characterization of resistance genes, mobile genetic elements (MGEs) and
      bacterial taxonomic compositions for 864 metagenomes from humans (n = 350),
      animals (n = 145) and external environments (n = 369), all deeply sequenced using
      Illumina technology. Environment types showed clear differences in both
      resistance profiles and bacterial community compositions. Human and animal
      microbial communities were characterized by limited taxonomic diversity and low
      abundance and diversity of biocide/metal resistance genes and MGEs but a
      relatively high abundance of ARGs. In contrast, external environments showed
      consistently high taxonomic diversity which in turn was linked to high diversity
      of both biocide/metal resistance genes and MGEs. Water, sediment and soil
      generally carried low relative abundance and few varieties of known ARGs, whereas
      wastewater/sludge was on par with the human gut. The environments with the
      largest relative abundance and/or diversity of ARGs, including genes encoding
      resistance to last resort antibiotics, were those subjected to industrial
      antibiotic pollution and a limited set of deeply sequenced air samples from a
      Beijing smog event. CONCLUSIONS: Our study identifies air and antibiotic-polluted
      environments as under-investigated transmission routes and reservoirs for
      antibiotic resistance. The high taxonomic and genetic diversity of external
      environments supports the hypothesis that these also form vast sources of unknown
      resistance genes, with potential to be transferred to pathogens in the future.

PMID- 27717409
TI  - A systematic review of measures of HIV/AIDS stigma in paediatric HIV-infected and
      HIV-affected populations.
AB  - INTRODUCTION: HIV-related stigma impacts the quality of life and care management
      of HIV-infected and HIV-affected individuals, but how we measure stigma and its
      impact on children and adolescents has less often been described. METHODS: We
      conducted a systematic review of studies that measured HIV-related stigma with a
      quantitative tool in paediatric HIV-infected and HIV-affected populations.
      RESULTS AND DISCUSSION: Varying measures have been used to assess stigma in
      paediatric populations, with most studies utilizing the full or variant form of
      the HIV Stigma Scale that has been validated in adult populations and utilized
      with paediatric populations in Africa, Asia and the United States. Other common
      measures included the Perceived Public Stigma Against Children Affected by HIV,
      primarily utilized and validated in China. Few studies implored item validation
      techniques with the population of interest, although scales were used in a
      different cultural context from the origin of the scale. CONCLUSIONS: Many stigma
      measures have been used to assess HIV stigma in paediatric populations, globally,
      but few have implored methods for cultural adaptation and content validity.

PMID- 27717411
TI  - Food as a tool for learning in everyday activities at preschool - an exploratory
      study from Sweden.
AB  - BACKGROUND: There is a need for research both in relation to food education at
      preschools and in relation to how the individual teacher can handle and relate to
      the many different scientific facts and paradigms that are prevalent in relation
      to food, health, and a sustainable lifestyle. OBJECTIVE: The aim of this study
      was to explore the experiences and meanings that preschool teachers associate
      with involving food as a tool for learning in planned educational activities.
      DESIGN: An exploratory study was conducted in 14 preschools with 131 teachers.
      Twenty semi-structured individual or group interviews with 45 preschool staff
      were conducted, and 10 interviews were selected for analysis. RESULTS: According
      to participants, both children and teachers developed a sensory language;
      children became more positive towards tasting and teachers discovered new
      possibilities for interdisciplinary work. However, the results also show that an
      allowing system, with both an interested and confident teacher who recognises the
      competent child and a supportive organisation, is needed in order to make food a
      meaningful tool for learning in preschool. DISCUSSION: According to previous
      studies, food has the potential to play an important part in everyday activities
      at preschool, both in planned educational activities as well as at meal
      situations. Our results imply that a holistic understanding of food in preschool
      is required for long-term work with food as a natural part of the everyday
      activities. CONCLUSION: The results imply that it is fun and meaningful for both
      children and teachers, and quite possible, to work with food as a tool for
      learning in everyday activities at preschool. In order to include food as a way
      to work with the preschool curriculum for a sustainable lifestyle, an allowing
      system is needed.

PMID- 27717412
TI  - Benefits of pharmacist-led flu vaccination services in community pharmacy.
AB  - Seasonal influenza is a major cause of excess winter deaths and increased
      hospital admissions. There is a high level of economic burden associated with the
      infection. Although vaccination targets have been set to tackle this
      international issue, many countries struggle to reach these coverage targets for
      their at-risk populations using traditional delivery methods. Traditional
      providers include family doctors and nurses; however, pharmacist-led influenza
      vaccination has become a more commonly utilised aid to support vaccination
      targets. Community pharmacies are convenient and widely accessible and
      evaluations consistently demonstrate that patients are satisfied with pharmacist
      led vaccinations. Allowing community pharmacists to administer influenza
      vaccination as an alternative option for delivery helps to increase the coverage
      rate of vaccination. In addition, commissioning community pharmacists to provide
      this service has been shown to contribute to achieving targets for those at-risk.
      Pharmacist-led influenza vaccination services can create value for payors and
      reduce pressure on health systems. This review aims to demonstrate the success of
      pharmacy-led influenza vaccinations, and the impact it has had in driving up
      immunisation rates within other countries. Experiences of countries such as
      England, Portugal and the United States provide evidence to demonstrate the
      benefit to both the patient and the health system.

PMID- 27717413
TI  - Implementation of flu vaccination in community pharmacies: Understanding the
      barriers and enablers.
AB  - Improving influenza vaccination coverage has been, and still remains a challenge
      internationally. There are now many examples where countries have pursued a
      pharmacist-led influenza vaccination service in order to enhance vaccination
      coverage of at-risk populations. England, Portugal and the United States are
      successful examples where their experience implementing this service can now be
      explored retrospectively and learnt from. This review aims to provide evidence to
      help overcome barriers to commissioning and implementation of such services in
      countries new to the experience. Implementation is influenced by differing
      regulatory frameworks underpinning the provision of pharmacist-led influenza
      vaccination, methods of remuneration, training, and operating procedures.
      Practical aspects such as the facilities required, how patient records are
      maintained and how patients and other healthcare professionals are engaged also
      have an impact. These examples illustrate how community pharmacists can be
      trained to deliver influenza vaccinations safely, and coupled with their
      accessibility and convenience, can provide a complementary service to that
      already provided by family doctors and nurses to deliver influenza vaccinations
      for the benefit of patients.

PMID- 27717414
TI  - Overview of Laboratory Testing and Clinical Presentations of Complement
      Deficiencies and Dysregulation.
AB  - Historically, complement disorders have been attributed to immunodeficiency
      associated with severe or frequent infection. More recently, however, complement
      has been recognized for its role in inflammation, autoimmune disorders, and
      vision loss. This paradigm shift requires a fundamental change in how complement
      testing is performed and interpreted. Here, we provide an overview of the
      complement pathways and summarize recent literature related to hereditary and
      acquired angioedema, infectious diseases, autoimmunity, and age-related macular
      degeneration. The impact of complement dysregulation in atypical hemolytic uremic
      syndrome, paroxysmal nocturnal hemoglobinuria, and C3 glomerulopathies is also
      described. The advent of therapeutics such as eculizumab and other complement
      inhibitors has driven the need to more fully understand complement to facilitate
      diagnosis and monitoring. In this report, we review analytical methods and
      discuss challenges for the clinical laboratory in measuring this complex
      biochemical system.

PMID- 27717415
TI  - Monitoring Oxygen Status.
AB  - Although part of a common "blood gas" test panel with pH and pCO2, the pO2,
      %O2Hb, and related parameters are independently used to detect and monitor oxygen
      deficits from a variety of causes. Measurement of blood gases and cooximetry may
      be done by laboratory analyzers, point of care testing, noninvasive pulse
      oximetry, and transcutaneous blood gases. The specimen type and mode of
      monitoring oxygenation that are chosen may be based on a combination of urgency,
      practicality, clinical need, and therapeutic objectives. Because oxygen
      concentrations in blood are extremely labile, there are several highly important
      preanalytical practices necessary to prevent errors in oxygen and cooximetry
      results. Effective utilization of oxygen requires binding by hemoglobin in the
      lungs, transport in the blood, and release to tissues, where cellular respiration
      occurs. Hydrogen ion (pH), CO2, temperature, and 2,3-DPG all play important roles
      in these processes. Additional measurements and calculations are often used to
      interpret and locate the cause and source of an oxygen deficit. These include the
      Hb concentration, Alveolar-arterial pO2 gradient, pO2:FIO2 ratio, oxygenation
      index, O2 content and O2 delivery, and pulmonary dead space and intrapulmonary
      shunting. The causes of hypoxemia will be covered and, to illustrate how the
      oxygen parameters are used clinically in the diagnosis and management of patients
      with abnormal oxygenation, two clinical cases will be presented and described.

PMID- 27717416
TI  - Microvesicles in Autoimmune Diseases.
AB  - During apoptosis or activation, cells can release a subcellular structure, called
      a membrane microvesicle (also known as microparticle) into the extracellular
      environment. Microvesicles bud-off as a portion of cell membrane with its
      associated proteins and lipids surrounding a cytosolic core that contains
      intracellular proteins, lipids, and nucleic acids (DNA, RNA, siRNA, microRNA,
      lncRNA). Biologically active molecules on the microvesicle surface and
      encapsulated within can act on recipient cells as a novel mode of intercellular
      communication. Apoptosis has long been known to be involved in the development of
      diseases of autoimmunity. Abnormally persistent microvesicles, particularly
      apoptotic microvesicles, can accelerate autoimmune responses locally in specific
      organs and tissues as well as systemically. In this review, we focus on studies
      implicating microvesicles in the pathogenesis of autoimmune diseases and their
      complications.

PMID- 27717417
TI  - Tandem Mass Spectrometry of Sphingolipids: Applications for Diagnosis of
      Sphingolipidoses.
AB  - In recent years, mass spectrometry (MS) has become the dominant technology in
      lipidomic analysis. It is widely used in diagnosis and research of lipid
      metabolism disorders including those characterized by impairment of lysosomal
      functions and storage of nondegraded-degraded substrates. These rare diseases,
      which include sphingolipidoses, have severe and often fatal clinical
      consequences. Modern MS methods have contributed significantly to achieve a
      definitive diagnosis, which is essential in clinical practice to begin properly
      targeted patient care. Here we summarize MS and tandem MS methods used for
      qualitative and quantitative analysis of sphingolipids (SL) relative to the
      diagnostic process for sphingolipidoses and studies focusing on alterations in
      cell functions due to these disorders. This review covers the following topics:
      Tandem MS is sensitive and robust in determining the composition of sphingolipid
      classes in various biological materials. Its ability to establish SL metabolomic
      profiles using MS bench-top analyzers, significantly benefits the first stages of
      a diagnosis as well as metabolic studies of these disorders. It can thus
      contribute to a better understanding of the biological significance of SL.

PMID- 27717418
TI  - Advances in Blood Typing.
AB  - The clinical importance of blood group antigens relates to their ability to evoke
      immune antibodies that are capable of causing hemolysis. The most important
      antigens for safe transfusion are ABO and D (Rh), and typing for these antigens
      is routinely performed for patients awaiting transfusion, prenatal patients, and
      blood donors. Typing for other blood group antigens, typically of the Kell,
      Duffy, Kidd, and MNS blood groups, is sometimes necessary, for patients who have,
      or are likely to develop antibodies to these antigens. The most commonly used
      typing method is serological typing, based on hemagglutination reactions against
      specific antisera. This method is generally reliable and practical for routine
      use, but it has certain drawbacks. In recent years, molecular typing has emerged
      as an alternative or supplemental typing method. It is based on detecting the
      polymorphisms and mutations that control the expression of blood group antigens,
      and using this information to predict the probable antigen type. Molecular typing
      methods are useful when traditional serological typing methods cannot be used, as
      when a patient has been transfused and the sample is contaminated with red blood
      cells from the transfused blood component. Moreover, molecular typing methods can
      precisely identify clinically significant variant antigens that cannot be
      distinguished by serological typing; this capability has been exploited for the
      resolution of typing discrepancies and shows promise for the improved transfusion
      management of patients with sickle cell anemia. Despite its advantages, molecular
      typing has certain limitations, and it should be used in conjunction with
      serological methods.

PMID- 27717419
TI  - Autoimmunity in Crohn's Disease-A Putative Stratification Factor of the Clinical
      Phenotype.
AB  - Inflammation in inflammatory bowel diseases (IBD) has been linked to a loss of
      tolerance to self-antigens suggesting the existence of autoantibodies in specific
      disease phenotypes. However, the lack of clearly defined autoantigenic targets
      has slowed down research. Genome-wide association studies have identified an
      impressive number of immune-related susceptibility loci for IBD with no clearly
      discernible pattern among them. Growing evidence supports the hypothesis that
      innate immune responses to a low-diversity and impaired gut microbiota may be of
      key importance in initiating and perpetuating chronic inflammation in IBD.
      Increasing evidence suggests that reduced microbial diversity and microbial
      mucosal epithelium interaction (including adhesion and clearance) are critically
      involved in IBD pathogenesis. Along these lines the discovery of autoantigenic
      targets in Crohn's disease (CD) has refocused research in IBD on the possible
      role of autoimmune responses. The identification of the major zymogen granule
      membrane glycoprotein 2 (GP2) as an autoantigen in CD patients and its proposed
      role in the sensing of the microbiota lends credence to this trend. Loss of
      tolerance to GP2 occurs in up to 40% of patients with CD. Corresponding
      autoantibodies appear to be associated with distinct disease courses (types or
      phenotypes) in CD. Here, we critically review autoantibodies in CD for their
      impact on clinical practice and future IBD research. The immunomodulatory role of
      GP2 in innate and adaptive intestinal immunity is also discussed.

PMID- 27717421
TI  - Omalizumab in the Treatment of Chronic Inducible Urticaria.
AB  - Omalizumab is a recombinant humanized monoclonal antibody that inhibits
      immunoglobulin E. It has been approved for the treatment of severe asthma and
      chronic spontaneous urticaria refractory to other treatments. Its use in the
      management of chronic inducible urticaria (a type triggered by certain stimuli)
      is still considered off-label, although this use has been discussed in some
      consensus papers. This review brings together case reports and case series
      describing the use of omalizumab to treat chronic inducible urticaria. We analyze
      the most important aspects of the cases and the outcomes reported. The results
      seem to position omalizumab as a potentially effective, safe treatment
      alternative in some cases of chronic inducible urticaria.

PMID- 27717422
TI  - Left Ventricular Assist Device Design Reduces von Willebrand Factor Degradation:
      A Comparative Study Between the HeartMate II and the EVAHEART Left Ventricular
      Assist System.
AB  - BACKGROUND: Supraphysiologic shear stress from continuous-flow left ventricular
      assist devices (LVADs) accelerates von Willebrand factor (vWF) degradation and
      predisposes patients to nonsurgical bleeding. It is unknown whether unique design
      characteristics of LVADs differentially affect vWF degradation. We tested the
      hypothesis that the centrifugal-flow EVAHEART (Evaheart, Houston, TX) left
      ventricular assist system (LVAS), which was designed to minimize shear stress
      (low operational revolutions per minute [rpm], larger flow gaps, low shear
      stress, flat H-Q curve), reduced vWF degradation versus the axial-flow HeartMate
      II (Thoratec, Pleasanton, CA) LVAD. METHODS: Whole human blood was obtained from
      volunteer donors (n = 22). Blood was circulated for 12 hours in mock circulatory
      loops through a HeartMate II (n = 10; 11,400 rpm, 6.3 +/- 0.8 L/min, 76 +/- 2 mm
      Hg) or an EVAHEART LVAS (n = 12; 2,300 rpm, 5.7 +/- 0.1 L/min, 80 +/- 1 mm Hg).
      vWF degradation was characterized with electrophoresis and immunoblotting for
      large vWF multimers and 11 vWF degradation fragments. RESULTS: The HeartMate II
      eliminated large vWF multimers and significantly (p < 0.05) increased 10 of 11
      vWF degradation fragments at 6 and 12 hours. The increase was approximately 2.0
      fold at 6 hours and 2.2-fold at 12 hours. In contrast, the EVAHEART LVAS modestly
      reduced large vWF multimers and significantly increased 5 of 11 and 8 of 11 vWF
      degradation fragments at 6 and 12 hours, respectively. The increase was
      approximately 1.5-fold at 6 hours and 1.7-fold at 12 hours. The EVAHEART LVAS
      caused significantly less degradation (p < 0.01) than the HeartMate II of the 140
      kDa vWF fragment (cleavage product of ADAMTS-13, the vWF protease). CONCLUSIONS:
      The EVAHEART LVAS caused significantly less vWF degradation than the HeartMate II
      in a mock circulatory loop with whole human blood. LVAD design features may
      minimize vWF degradation. These data may inform the design and operation of next
      generation LVADs to minimize blood trauma.

PMID- 27717423
TI  - Conduction Disorders After Sutureless Aortic Valve Replacement.
AB  - BACKGROUND: Sutureless self-expandable aortic bioprostheses rely on radial forces
      for stabilization, raising concern that these devices may increase the risk of
      postoperative conduction disease. The purpose of this study was to determine the
      incidence of conduction disorders after sutureless aortic valve replacement (AVR)
      with the Perceval S (Sorin Group, Saluggia, Italy) bioprosthesis. METHODS:
      Between June 2011 and March 2013, 108 consecutive patients underwent sutureless
      AVR with the Perceval S prosthesis. Six patients (6%) had a permanent pacemaker
      (PPM) preoperatively and were excluded from the present study. Mean
      electrocardiographic follow-up was 14.6 +/- 6.0 months. RESULTS: Mean age was
      79.2 +/- 4.8 years (52% female). During the postoperative period, 34 patients
      (34%) had first-degree atrioventricular block, 2 (2%) had Mobitz-II
      atrioventricular block, and 16 (16%) had complete atrioventricular block. New
      onset left bundle branch block and right bundle branch block were observed in 33
      patients (33%) and 22 patients (22%), respectively. Inhospital postoperative PPM
      implantation was required in 23 patients (23%). Preoperative aortic valve area,
      age more than 85 years, and preoperative right bundle branch block were found to
      be independently associated with inhospital PPM implantation or new-onset
      postoperative conduction disorder. At follow-up, 3 more patients (3%) underwent
      PPM implantation. The cumulative incidences of PPM dependency and ventricular
      pacing more than 25% of the time were 18% +/- 11% and 21% +/- 10%, respectively,
      at 18 months. CONCLUSIONS: In the present study, the postoperative PPM
      implantation rate (23%) after sutureless AVR with the Perceval S prosthesis was
      high. Surgical strategies aimed at mitigating this risk should be further
      investigated.

PMID- 27717424
TI  - The Role of Echocardiography and Intracardiac Exploration in the Evaluation of
      Candidacy for Biventricular Repair in Patients With Borderline Left Heart
      Structures.
AB  - BACKGROUND: Predictors for single ventricle palliation (SVP) or successful
      biventricular repair (BVR) in patients with borderline left-side heart structures
      are not well defined. The goal was to evaluate the role of echocardiography and
      intracardiac exploration in determining feasibility of BVR. METHODS: All neonates
      surgically treated from 1995 to 2015 with mitral valve (MV), aortic valve, or
      left ventricle end-diastolic dimension z score of -2 or less for whom management
      was controversial were included. Data were analyzed using Fisher's exact test,
      Kruskal-Wallis test, and Kaplan-Meier analysis. RESULTS: The cohort consisted of
      42 patients: 7 SVP (17%) and 35 BVR (83%). Median follow-up was 7 years (range, 6
      months to 18 years). Intracardiac exploration was performed in 29 patients (69%).
      There was poor correlation between echocardiographic and intraoperative MV
      measurements (intraclass correlation coefficient 0.14). Preoperative
      echocardiography significantly underestimated MV size in 14 patients (54%). Two
      BVR patients were converted to SVP, and 4 (including 1 converted patient) had
      cardiac-related deaths. All patients with MV greater than 8 mm on preoperative
      echocardiography had successful BVR. An intraoperative MV less than 8 mm and an
      abnormal subvalvar apparatus was present in 5 of 6 SVP (83%) and 3 of 3 (100%)
      failed BVR patients who had intracardiac exploration, and in only 1 of 20
      successful BVR patients (5%) who had an intracardiac exploration. CONCLUSIONS:
      The decision to proceed to BVR in patients with borderline left-side heart
      structures should not rely strictly on echocardiographic measurements.
      Intracardiac exploration of the MV and subvalvar apparatus is useful before
      committing a patient to SVP. Patients with low MV z scores, especially those with
      a normal subvalvar apparatus, may undergo BVR with good outcomes.

PMID- 27717425
TI  - The Association Between Urine Output, Creatinine Elevation, and Death.
AB  - BACKGROUND: Acute kidney injury can be defined by a fall in urine output, and
      urine output criteria may be more sensitive in identifying acute kidney injury
      than traditional serum creatinine criteria. However, as pointed out in the Kidney
      Disease Improving Global Outcome guidelines, the association of urine output with
      subsequent creatinine elevations and death is poorly characterized. The purpose
      of this study was to determine what degrees of reduced urine output are
      associated with subsequent creatinine elevation and death. METHODS: This was a
      retrospective cohort study of adult patients (age >=18 years) cared for in a
      cardiovascular intensive care unit after undergoing cardiac operations in a
      tertiary care university medical center. All adult patients who underwent cardiac
      operations and were not receiving dialysis preoperatively were studied. The
      development of acute kidney injury was defined as an increase in creatinine of
      more than 0.3 mg/dL or by more than 50% above baseline by postoperative day 3.
      RESULTS: Acute kidney injury developed in 1,061 of 4,195 patients (25%). Urine
      output had moderate discrimination in predicting subsequent acute kidney injury
      (C statistic = .637 +/- .054). Lower urine output and longer duration of low
      urine output were associated with greater odds of developing acute kidney injury
      and death. CONCLUSIONS: We found that there is similar accuracy in using urine
      output corrected for actual, ideal, or adjusted weight to discriminate future
      acute kidney injury by creatinine elevation and recommend using actual weight for
      its simplicity. We also found that low urine output is associated with subsequent
      acute kidney injury and that the association is greater for lower urine output
      and for low urine output of longer durations. Low urine output (<0.2 mL . kg-1 .
      h-1), even in the absence of acute kidney injury by creatinine elevation, is
      independently associated with mortality.

PMID- 27717426
TI  - The Racial Paradox in Multiarterial Conduit Utilization for Coronary Artery
      Bypass Grafting.
AB  - BACKGROUND: It has been established that outcomes for black patients undergoing
      coronary artery bypass graft surgery (CABG) are inferior to those of their white
      counterparts. The purpose of this study was to determine (1) whether rates of
      multiarterial grafting are different among black patients and white patients, and
      (2) whether racial differences exist in postoperative outcomes after accounting
      for grafting strategy. METHODS: A retrospective review of black patients (n =
      2,810) and white patients (n = 13,569) who underwent isolated, primary CABG from
      January 2002 to June 2014 at a US academic institution was performed. A modified
      predicted risk of mortality (M-PROM) score was calculated for each patient using
      all The Society of Thoracic Surgeons variables for CABG excluding race.
      Multivariable linear, logistic, and Cox regression analyses were used to assess
      between-group differences, adjusted for M-PROM. RESULTS: Overall, 16,379 patients
      underwent CABG, and 2,441 (14.9%) received more than one arterial graft. When
      adjusted for M-PROM, the odds of blacks undergoing multiarterial CABG were 10%
      greater than for whites (p = 0.05). Blacks had worse inhospital outcomes,
      including higher odds of stroke (odds ratio 2.41, 95% confidence interval [CI]:
      1.80 to 3.25) and prolonged intubation (odds ratio 2.01, 95% CI: 1.77 to 2.28).
      The increase in postoperative complications did not translate to a difference in
      inhospital mortality (p = 0.10) between racial cohorts. Moreover, among patients
      who underwent multiarterial grafting strategies, blacks had a hazard of mortality
      that was 34% higher (95% CI: 22% to 51%)) than that of their white counterparts.
      Among black patients, those who underwent multiarterial grafting strategies
      showed better long-term survival than those undergoing single grafting strategies
      (hazard ratio 0.86, 95% CI: 0.78 to 0.96). CONCLUSIONS: Despite similar rates of
      arterial grafting for black patients and white patients in this large single
      center cohort, black patients continued to have significantly worse late survival
      when compared with white patients. Continued evaluation as to the causes of this
      disparity is warranted.

PMID- 27717428
TI  - The Role of Human Papilloma Virus in Penile Carcinogenesis and Preneoplastic
      Lesions: A Potential Target for Vaccination and Treatment Strategies.
AB  - Penile cancer is a rare and devastating disease, especially at advanced stages.
      The etiology of penile cancer is multifactorial with multiple established risk
      factors including infection with the human papillomavirus (HPV). Approximately
      40% of penile cancers are attributable to HPV, although the literature describing
      HPV as a prognostic factor is mixed. The pathogenesis of HPV infection as well as
      vaccination practices may provide valuable therapeutic agents to treat this rare
      and difficult disease.

PMID- 27717427
TI  - Should We Perform Carotid Doppler Screening Before Surgical or Transcatheter
      Aortic Valve Replacement?
AB  - BACKGROUND: Screening for internal carotid artery stenosis (ICAS) with Doppler
      ultrasound is commonly used before cardiovascular surgery. Nevertheless, the
      relationship between ICAS and procedure-related stroke in isolated aortic valve
      replacement is unclear. METHODS: We retrospectively reviewed patients with artery
      stenosis who underwent ICAS screening before surgical (SAVR) or transcatheter
      aortic valve replacement (TAVR) between January 2007 and August 2014. Logistic
      regression models were used to determine the relation between post-procedure
      stroke and total (sum of left and right ICAS) and maximal unilateral ICAS. Age,
      sex, history of atrial fibrillation, cerebrovascular disease and diabetes, left
      ventricular ejection fraction, and procedure type were considered as covariates.
      Two-subgroup analyses were performed in patients who underwent TAVR and SAVR,
      adjusting for procedure specific details. RESULTS: A total of 996 patients
      underwent ICAS screening before TAVR (n = 467) or SAVR (n = 529). The prevalence
      of at least >=70% ICAS was 5.2% (n = 52) and incidence of 30-day stroke was 3.4%
      (n = 34). Eight patients who underwent carotid intervention before valve
      replacement and 6 patients with poor Doppler images were excluded from the final
      analysis. We found no statistically significant association between stroke and
      either the total or maximal unilateral ICAS for all patients (p = 0.13 and p =
      0.39, respectively) or those undergoing TAVR (p = 0.27 and p = 0.63,
      respectively) or SAVR (p = 0.21 and p = 0.36, respectively). CONCLUSIONS: We
      found no statistically significant association between ICAS severity procedure
      related stroke after aortic valve replacement. This suggests that universal
      carotid Doppler screening before isolated TAVR or SAVR is unnecessary.

PMID- 27717429
TI  - Advances in Penile-Preserving Surgical Approaches in the Management of Penile
      Tumors.
AB  - Penile-preserving surgery offers a revolutionary alternative to more traditional
      radical surgery. It offers better sexual, functional, and psychological results
      and evidence suggests it achieves this without sacrificing oncological outcomes.
      We examined the evolving nature of such surgeries, addressing controversies such
      as safe margins and survival outcomes and discussing more conventional
      techniques, including laser. At our UK center, we treat a high volume of penile
      cancer and here, based on such experience, we describe our glans resurfacing,
      glansectomy, and partial penectomy techniques; their application by disease
      stage; and the limitations of such surgeries.

PMID- 27717430
TI  - Contemporary Role of Radiotherapy in the Management of Primary Penile Tumors and
      Metastatic Disease.
AB  - Squamous cell cancer of the penis is a radiocurable malignancy all too often
      managed solely by partial or total penectomy. Effective management of the primary
      tumor while preserving penile morphology and function is a priority. External
      radiotherapy and brachytherapy have a role to play in the definitive management
      of the primary tumor. Surgical nodal staging remains a cornerstone of management
      because it is the strongest predictor of survival, and inguinal status determines
      pelvic management. Postoperative radiotherapy of the regional nodes for high-risk
      pathology is indicated. Chemoradiotherapy should be considered as neoadjuvant
      treatment for unresectable nodes or as definitive management.

PMID- 27717432
TI  - Surgical Advances in Inguinal Lymph Node Dissection: Optimizing Treatment
      Outcomes.
AB  - Lymphadenectomy (LND) for locally advanced penile cancer is often necessary in
      patients with suspected disease within the inguinal or pelvic lymph nodes because
      the results of systemic therapy are somewhat marginal. It has utility in staging,
      disease prognosis, and treatment in certain men because early dissection of
      involved lymph nodes improves survival. Despite its mainstay in the management of
      this disease, inguinal and pelvic lymph node dissection can be associated with
      significant postoperative complications and patient morbidity. Recent refinements
      in surgical technique, however, and appropriate patient selection can minimize
      these risks and lead to better short-term and long-term outcomes.

PMID- 27717431
TI  - Minimal Invasive Management of Lymph Nodes.
AB  - Penile cancer is a rare genitourinary malignancy. Lymph node involvement is the
      single most important factor determining survival in these patients, and those
      patients with occult disease are difficult to identify on conventional cross
      sectional imaging. Until recently, lymph node sampling (eg, lymphadenectomy) has
      been the diagnostic modality of choice in the detection of micrometastasis. More
      recently, several novel molecular and minimally invasive diagnostic techniques
      have been developed, which have been demonstrated to decrease the false-negative
      and -positive results of conventional imaging and lymphadenectomy. This article
      focuses on the minimally invasive management of lymph nodes in men with penile
      cancer.

PMID- 27717433
TI  - Multimodal Therapy in the Management of Advanced Penile Cancer.
AB  - A multimodal approach to therapy is increasingly used in treating men with
      advanced penile cancer. Adjuvant chemotherapy improves outcomes in chemotherapy
      naive men with node-positive positive disease, and neoadjuvant chemotherapy can
      downstage bulky nodal disease sufficiently to permit surgery and has the
      potential to offer durable long-term survival. However, there remain several
      unanswered questions in this field, and international collaboration in the form
      of clinical trials is required to optimize treatment and improve survival in men
      with advanced penile cancer.

PMID- 27717434
TI  - Emerging Systemic Therapies for the Management of Penile Cancer.
AB  - Penile squamous cell carcinoma (PSCC) is a rare cancer, but is more common in
      developing countries. Locally advanced and metastatic PSCC is associated with
      significant morbidity and mortality, with the prognosis remaining extremely poor.
      The authors searched PubMed and published abstracts for metastatic PSCC studies
      to describe emerging therapies. Multimodality treatment using chemotherapy,
      radiation, and consolidative surgery are standard of care. Utilizing anti-EGFR
      therapies and novel immunotheraputic approaches may help improve outcomes in
      PSCC.

PMID- 27717435
TI  - Contemporary Management of Primary Distal Urethral Cancer.
AB  - Primary urethral cancer is one of the rare urologic tumors. Distal urethral
      tumors are usually less advanced at diagnosis compared with proximal tumors and
      have a good prognosis if treated appropriately. Low-stage distal tumors can be
      managed successfully with a surgical approach in men or radiation therapy in
      women. There are no clear-cut indications for the choice of the most appropriate
      treatment modality. Organ-preserving modalities have shown effective and should
      be used whenever they do not compromise the oncological safety to decrease the
      physical and psychological trauma of dismemberment or loss of sexual/urinary
      function.

PMID- 27717436
TI  - Management of Proximal Primary Urethral Cancer: Should Multidisciplinary Therapy
      Be the Gold Standard?
AB  - Primary urethral cancer (PUC) is a rare, but devastating genitourinary tumor that
      affects men and women. Although most PUC are localized, proximal PUC frequently
      presents with locally advanced disease, with 30% to 40% having lymph node
      metastasis. Single modality surgical or radiation therapy has dismal results.
      Multimodal therapy with cisplatin-based chemotherapy and consolidation surgery
      has greatly improved the local recurrence and overall survival rates for this
      aggressive disease. In locally advanced squamous cell carcinoma of the urethra,
      radiotherapy combined with radiosensitizing chemotherapy is an option for genital
      preservation. Prospective, multi-institutional studies are required to further
      define the optimal multidisciplinary treatment strategy for this destructive
      disease.

PMID- 27717437
TI  - Management of Urethral Recurrences: Urothelial and Nonurothelial.
AB  - This article discusses the diagnostic and therapeutic options in the management
      of urethral cancer recurrence in patients treated with urethral sparing
      cystectomy as well as those who had urethral preservation following primary
      urethral carcinoma.

PMID- 27717438
TI  - Preneoplastic and Primary Scrotal Cancer: Updates on Pathogenesis and Diagnostic
      Evaluation.
AB  - Occupational exposure has been causally linked to scrotal cancer. Primary
      preventative care and avoiding carcinogenic substances have decreased the
      incidence and changed the treatment of scrotal cancer. The current incidence of
      scrotal malignancy is approximately 1 per 1,000,000 male persons/year. The rarity
      of cases and of research impedes our understanding of the changing nature of
      scrotal cancer. This article summarizes the current knowledge, focusing mainly on
      pathogenesis and diagnostic evaluation, which may influence prevention and early
      recognition of the disease. We stratify scrotal cancer into common histologic
      subtypes: squamous cell carcinoma, extramammary Paget's disease, and basal cell
      carcinoma.

PMID- 27717439
TI  - Surgical Management of Primary Scrotal Cancer.
AB  - Primary scrotal cancer is a rare urologic malignancy with various histologic
      subtypes. Management and outcomes are not designed optimally. Surgical excision
      is the recommended treatment for localized scrotal cancer, with assessment of the
      margins for disease. Closure of the defect can be performed with primary closure,
      skin grafts, flaps, or by secondary intention. Analysis of outcomes suggests that
      high-risk scrotal cancer may have a worse prognosis compared with penile cancer,
      and low-risk scrotal cancer may have a comparable prognosis. Understanding
      techniques for management and survival outcomes can help the urologist determine
      the appropriate course of treatment and improve patient care.

PMID- 27717440
TI  - Advances in Surgical Reconstructive Techniques in the Management of Penile,
      Urethral, and Scrotal Cancer.
AB  - This article reviews the most up-to-date surgical treatment options for the
      reconstructive management of patients with penile, urethral, and scrotal cancer.
      Each organ system is examined individually. Techniques and discussion for penile
      cancer reconstruction include Mohs surgery, glans resurfacing, partial and total
      glansectomy, and phalloplasty. Included in the penile cancer reconstruction
      section is the use of penile prosthesis in phalloplasty patients after penectomy,
      tissue engineering in phallic regeneration, and penile transplantation.
      Reconstruction following treatment of primary urethral carcinoma and current
      techniques for scrotal cancer reconstruction using split-thickness skin grafts
      and flaps are described.

PMID- 27717441
TI  - Penile, Urethral, and Scrotal Cancer.

PMID- 27717442
TI  - Penile, Urethral, and Scrotal Cancer.

PMID- 27717443
TI  - Impact of Gender on the Prognostic Value of Coronary Artery Calcium in
      Symptomatic Patients With Normal Single-Photon Emission Computed Tomography
      Myocardial Perfusion.
AB  - The coronary artery calcium (CAC) score provides independent prognostic value on
      top of single-photon emission computed tomography (SPECT) myocardial perfusion
      imaging (MPI). We sought to determine whether the prognostic value of the CAC
      score in patients with normal SPECT MPI is gender specific. We studied 3,705
      consecutive symptomatic patients without a history of coronary artery disease
      with normal SPECT MPI. All patients underwent concomitant CAC scoring, which was
      categorized as CAC score 0, 1 to 99, 100 to 399, 400 to 999, or >=1,000. Major
      adverse cardiac events were defined as revascularization, nonfatal myocardial
      infarction, or all-cause mortality. The median CAC score was 9 in women
      (interquartile range 0 to 113) and 47 in men (interquartile range 1 to 307, p
      <0.001). The annual event rate was lower in women than in men (1.6% and 2.7%,
      respectively, p <0.001). When stratified by CAC score, annual event rates were
      similar (for women and men, respectively: CAC score 0, 0.6% and 0.5%, p = 0.95;
      CAC score 1 to 99, 0.9% and 1.2%, p = 0.45; CAC score 100 to 399, 2.7% and 3.8%,
      p = 0.23; CAC score 400 to 999, 3.8% and 5.3%, p = 0.34; CAC score >=1,000, 8.4%
      and 8.7%, p = 0.99). The CAC score was an independent predictor of major adverse
      cardiac events in both genders (CAC score >=1,000: hazard ratio for women 8.5,
      95% confidence interval 4.0 to 18.1; hazard ratio for men 14.8, 95% confidence
      interval 5.3 to 41.1). In conclusion, risk for events is similar for both genders
      when stratified by CAC score, wherein a high CAC score carries a high risk for
      events despite normal SPECT MPI. Our findings do not reveal a gender-specific
      prognostic value of the CAC score.

PMID- 27717444
TI  - Novel insights of ethylene role in strawberry cell wall metabolism.
AB  - Due to its organoleptic and nutraceutical qualities, strawberry fruit (Fragaria x
      ananassa, Duch) is a worldwide important commodity. The role of ethylene in the
      regulation of strawberry cell wall metabolism was studied in fruit from Toyonoka
      cultivar harvested at white stage, when most changes associated with fruit
      ripening have begun. Fruit were treated with ethephon, an ethylene-releasing
      reagent, or with 1-methylcyclopropene (1-MCP), a competitive inhibitor of
      ethylene action, maintaining a set of non-treated fruit as controls for each
      condition. Ethephon treated-fruit showed higher contents of hemicelluloses,
      cellulose and neutral sugars regarding controls, while 1-MCP-treated fruit showed
      a lower amount of those fractions. On the other hand, ethephon-treated fruit
      presented a lower quantity of galacturonic acid from ionically and covalently
      bound pectins regarding controls, while 1-MCP-treated fruit showed higher
      contents of those components. We also explored the ethylene effect over the mRNA
      accumulation of genes related to pectins and hemicelluloses metabolism, and a
      relationship between gene expression patterns and cell wall polysaccharides
      contents was shown. Moreover, we detected that strawberry necrotrophic pathogens
      growth more easily on plates containing cell walls from ethephon-treated fruit
      regarding controls, while a lower growth rate was observed when cell walls from 1
      MCP treated fruit were used as the only carbon source, suggesting an effect of
      ethylene on cell wall structure. Around 60% of strawberry cell wall is made up of
      pectins, which in turns is 70% made by homogalacturonans. Our findings support
      the idea of a central role for pectins on strawberry fruit softening and a
      participation of ethylene in the regulation of this process.

PMID- 27717445
TI  - miRNA alterations are important mechanism in maize adaptations to low-phosphate
      environments.
AB  - Maize is a globally important crop, and a low phosphate (LP) supply frequently
      limits maize yields in many areas. microRNAs (miRNAs) play important roles in
      plant development and environmental adaptation. In this study, spatio-temporal
      miRNA transcript profiling and some of the target genes in the roots and leaves
      of the maize inbred line Q319 were analyzed in response to LP. Complex small RNA
      populations were detected after LP culture, and they displayed different patterns
      in the roots and leaves. Differentially expressed miRNAs can be grouped into
      'early' miRNAs, which respond rapidly and are often non-specific to phosphate
      deficiency, and 'late' miRNAs, which alter the morphology, physiology or
      metabolism of plants upon prolonged phosphate deficiency. miR827 and miR399
      mediated posttranscriptional pathway responses to phosphate availability were
      conserved and species-specific in maize. Abiotic stress-related miRNAs were
      engaged in interactions with different signaling and/or metabolic pathways. Auxin
      related miRNAs and their targets' expression may be involved in root architecture
      modification and upland growth retardation in maize when subjected to LP. The
      changes that were found in the expression of miRNAs and their target genes
      suggested that miRNA regulation/alterations are pivotal mechanisms in maize
      adaptations to LP environments. A complex regulatory mechanism involving miRNAs
      in response to the LP environment is present in maize.

PMID- 27717446
TI  - Arginine-rich motif-tandem CCCH zinc finger proteins in plant stress responses
      and post-transcriptional regulation of gene expression.
AB  - Tandem CCCH zinc finger (TZF) proteins are evolutionarily conserved regulators of
      gene expression at the post-transcriptional level. TZFs target AU-rich RNA
      elements at 3' un-translated region and recruit catabolic machineries to trigger
      mRNA degradation. The plant TZF families are over-represented by a class of
      proteins with a unique TZF domain preceded by an arginine-rich motif (RR-TZF). RR
      TZF proteins are mainly involved in hormone- and environmental cues-mediated
      plant growth and stress responses. Numerous reports have suggested that RR-TZF
      proteins control seed germination, plant size, flowering time, and biotic and
      abiotic stress responses via regulation of gene expression. Despite growing
      genetic evidence, the underlying molecular mechanisms are elusive. This review
      outlines the highly conserved roles of plant RR-TZFs in various stress responses
      and the potential involvements of RR-TZF proteins in transcriptional and post
      transcriptional regulation of gene expression. The dynamic subcellular
      localization of RR-TZF proteins, implication of predominant protein-protein
      interactions between RR-TZF proteins and stress response mediators and future
      directions of this research field are also discussed.

PMID- 27717447
TI  - Arabidopsis clade IV TGA transcription factors, TGA10 and TGA9, are involved in
      ROS-mediated responses to bacterial PAMP flg22.
AB  - Reactive oxygen species (ROS) produced in chloroplasts have been proposed to act
      as signaling molecules for plant immunity through pathogen-associated molecular
      patterns (PAMPs), such as flg22. To elucidate this process, we herein conducted
      genetic screening of flg22-sensitive mutants from T-DNA insertion lines lacking
      chloroplastic H2O2-responsive genes. The results obtained showed that knockout
      mutants lacking a clade IV TGA transcription factor, TGA10, were more sensitive
      to the flg22 treatment than wild-type plants. Furthermore, although no flg22
      sensitive phenotype was detected in the knockout mutant of another clade IV TGA9,
      double knockout tga9 tga10 mutants showed more sensitivity to flg22 than single
      knockout mutants. Transcripts of TGA10 and TGA9 were strongly induced by flg22 in
      leaves, and this was facilitated by the double knockout of stromal and thylakoid
      bound ascorbate peroxidases (APX), which are major H2O2 scavengers in
      chloroplasts. The flg22-induced H2O2 accumulation was maintained at high level in
      these APXs mutants, indicating the clade IV TGAs may be induced by the ROS.
      Furthermore, TGA10 was required for the complete activation of the expression of
      several flg22-responsive genes in plants treated with this PAMP. These have
      provided a new insight into the relationship between the TGA transcription
      factors and ROS-mediated signaling in PAMPs responses.

PMID- 27717448
TI  - Glu-370 in the large subunit influences the substrate binding, allosteric, and
      heat stability properties of potato ADP-glucose pyrophosphorylase.
AB  - ADP-glucose pyrophosphorylase (AGPase) is a key allosteric enzyme in plant starch
      biosynthesis. Plant AGPase is a heterotetrameric enzyme that consists of large
      (LS) and small subunits (SS), which are encoded by two different genes. In this
      study, we showed that the conversion of Glu to Gly at position 370 in the LS of
      AGPase alters the heterotetrameric stability along with the binding properties of
      substrate and effectors of the enzyme. Kinetic analyses revealed that the
      affinity of the LSE370GSSWT AGPase for glucose-1-phosphate is 3-fold less than
      for wild type (WT) AGPase. Additionally, the LSE370GSSWT AGPase requires 3-fold
      more 3-phosphogyceric acid to be activated. Finally, the LSE370GSSWTAGPase is
      less heat stable compared with the WT AGPase. Computational analysis of the
      mutant Gly-370 in the 3D modeled LS AGPase showed that this residue changes
      charge distribution of the surface and thus affect stability of the LS AGPase and
      overall heat stability of the heterotetrameric AGPase. In summary, our results
      show that LSE370 intricately modulate the heat stability and enzymatic activity
      of potato the AGPase.

PMID- 27717449
TI  - GL2-type homeobox gene Roc4 in rice promotes flowering time preferentially under
      long days by repressing Ghd7.
AB  - Under long day (LD) lengths, flowering can be delayed in rice by modulating
      several regulatory genes. We found activation tagging lines that showed an early
      flowering phenotype preferentially under LD conditions. Expression of Rice
      outermost cell-specific gene 4 (Roc4), encoding a homeodomain Leu-zipper class IV
      family protein, was significantly increased. Transcript levels of Grain number,
      plant height, and heading date7 (Ghd7) were significantly reduced while those of
      Ghd7 downstream genes were increased. However, other flowering regulators were
      unaffected. Whereas constitutive overexpression of Roc4 in 'Dongjin' japonica
      rice, which carries active Ghd7, also caused LD-preferential early flowering, its
      overexpression in 'Longjing27' rice, which is defective in functional Ghd7, did
      not produce the same result. This confirmed that Roc4 regulates flowering time
      mainly through Ghd7. Phytochromes and O. sativa GIGANTEA (OsGI) function upstream
      of Roc4. Transgenic plants showed ubiquitous expression of the beta-glucuronidase
      reporter gene under the Roc4 promoter. Furthermore, Roc4 had transcriptional
      activation activity in the N-terminal region of the StAR-related lipid-transfer
      domain. All of these findings are evidence that Roc4 is an LD-preferential
      flowering enhancer that functions downstream of phytochromes and OsGI, but
      upstream of Ghd7.

PMID- 27717451
TI  - ABA accumulation in water-stressed Citrus roots does not rely on carotenoid
      content in this organ.
AB  - Sustained abscisic acid (ABA) accumulation in dehydrated citrus roots depends on
      the transport from aerial organs. Under this condition, the role of the beta,beta
      carotenoids (ABA precursors) to the de novo synthesis of ABA in roots needs to be
      clarified since their low availability in this organ restricts its accumulation.
      To accomplish that, detached citrus roots were exposed to light (to increase
      their carotenoid content) and subsequently dehydrated (to trigger ABA
      accumulation). Stress imposition sharply decreased the pool of beta,beta
      carotenoids but, unexpectedly, no concomitant rise in ABA content was observed.
      Contrastingly, roots of intact plants (with low levels of carotenoids) showed a
      similar decrease of ABA precursor together with a significant ABA accumulation.
      Furthermore, upon dehydration both types of roots showed similar upregulation of
      the key genes involved in biosynthesis of carotenoids and ABA (CsPSY3a;
      CsbetaCHX1; CsbetaCHX2; CsNCED1; CsNCED2), demonstrating a conserved
      transcriptional response triggered by water stress. Thus, the sharp decrease in
      root carotenoid levels in response to dehydration should be related to other
      stress-related signals instead of contributing to ABA biosynthesis. In summary,
      ABA accumulation in dehydrated-citrus roots largely relies on the presence of the
      aerial organs and it is independent of the amount of available root beta,beta
      carotenoids.

PMID- 27717450
TI  - Sucrose-induced anthocyanin accumulation in vegetative tissue of Petunia plants
      requires anthocyanin regulatory transcription factors.
AB  - The effects of three different sucrose concentrations on plant growth and
      anthocyanin accumulation were examined in non-transgenic (NT) and transgenic (T2)
      specimens of the Petunia hybrida cultivar 'Mirage rose' that carried the
      anthocyanin regulatory transcription factors B-Peru+mPAP1 or RsMYB1. Anthocyanin
      accumulation was not observed in NT plants in any treatments, whereas a range of
      anthocyanin accumulation was observed in transgenic plants. The anthocyanin
      content detected in transgenic plants expressing the anthocyanin regulatory
      transcription factors (B-Peru+mPAP1 or RsMYB1) was higher than that in NT plants.
      In addition, increasing sucrose concentration strongly enhanced anthocyanin
      content as shown by quantitative real-time polymerase chain reaction (qRT-PCR)
      analysis, wherein increased concentrations of sucrose enhanced transcript levels
      of the transcription factors that are responsible for the induction of
      biosynthetic genes involved in anthocyanin synthesis; this pattern was not
      observed in NT plants. In addition, sucrose affected plant growth, although the
      effects were different between NT and transgenic plants. Taken together, the
      application of sucrose could enhance anthocyanin production in vegetative tissue
      of transgenic Petunia carrying anthocyanin regulatory transcription factors, and
      this study provides insights about interactive effects of sucrose and
      transcription factors in anthocyanin biosynthesis in the transgenic plant.

PMID- 27717452
TI  - Molecular and genetic characterization of a self-compatible apple cultivar, 'CAU
      1'.
AB  - In this study, we characterized a naturally occurring self-compatible apple
      cultivar, 'CAU-1' (S1S9), and studied the underlying mechanism that causes its
      compatibility. Analyses of both fruit set rate and seed number after self
      pollination or cross-pollination with 'Fuji' (S1S9), and of pollen tube growth,
      demonstrated that 'CAU-1' is self-compatible. Genetic analysis by S-RNase PCR
      typing of selfed progeny of 'CAU-1' revealed the presence of all progeny classes
      (S1S1, S1S9, and S9S9). Moreover, no evidence of S-allele duplication was found.
      These findings support the hypothesis that loss of function of an S-locus
      unlinked pollen-part mutation (PPM) expressed in pollen, rather than a natural
      mutation in the pollen-S gene (S1- and S9- haplotype), leads to SI breakdown in
      'CAU-1'. In addition, there were no significant differences in pollen morphology
      or fertility between 'Fuji' and 'CAU-1'. However, we found that the effect of S1-
      and S9-RNase on the SI behavior of pollen could not be addressed better in 'CAU
      1' than in 'Fuji'. Furthermore, we found that a pollen-expressed hexose
      transporter, MdHT1, interacted with S-RNases and showed significantly less
      expression in 'CAU-1' than in 'Fuji' pollen tubes. These findings support the
      hypothesis that MdHT1 may participate in S-RNase internalization during the SI
      process, and decrease of MdHT1 expression in 'CAU-1' hindered the release of self
      S-RNase into the cytoplasm of pollen tubes, thereby protecting pollen from the
      cytotoxicity of S-RNase, finally probably resulting in self-compatibility.
      Together, these findings indicate that S-locus external factors are required for
      gametophytic SI in the Rosaceae subtribe Pyrinae.

PMID- 27717453
TI  - Synergies and antagonisms in virus interactions.
AB  - Metagenomic surveys and data from next generation sequencing revealed that mixed
      infections among plant viruses are probably a rule rather than an exception in
      natural pathosystems. The documented cases may range from synergism to
      antagonism, which may depend from the spatiotemporal order of arrival of the
      viruses on the host and upon the host itself. In synergistic interactions, the
      measurable differences in replication, phenotypic and cytopathological changes,
      cellular tropism, within host movement, and transmission rate of one of the two
      viruses or both are increased. Conversely, a decrease in replication, or
      inhibition of one or more of the above functions by one virus against the other,
      leads to an antagonistic interaction. Viruses may interact directly and by
      transcomplementation of defective functions or indirectly, through responses
      mediated by the host like the defense mechanism based on RNA silencing. Outcomes
      of these interactions can be applied to the risk assessment of transgenic crops
      expressing viral proteins, or cross-protected crops for the identification of
      potential hazards. Prior to experimental evidence, mathematical models may help
      in forecasting challenges deriving from the great variety of pathways of
      synergistic and antagonistic interactions. Actually, it seems that such
      predictions do not receive sufficient credit in the framework of agriculture.

PMID- 27717454
TI  - Short versus long term effects of cyanide on sugar metabolism and transport in
      dormant walnut kernels.
AB  - Tree seed dormancy release by cold stratification accompanies with the embryo
      increased gluconeogenesis competence. Cyanide also breaks seed dormancy however,
      integrated information about its effects on carbon metabolism is lacking.
      Accordingly, the impacts of HCN on germination, lipid gluconeogenesis and sugar
      transport capacity of walnut (Juglans regia L.) kernels were investigated during
      10-days period prior to radicle protrusion. HCN increased walnut kernel
      germination and within four days of kernel incubation, hastened the decline of
      starch, reducing and non-reducing sugars and led to greater activities of
      alkaline invertase and glucose-6-phosphate dehydrogenase. From four days of
      kernel incubation onwards, starch and non-reducing sugars accumulated only in the
      HCN treated axes. Cyanide also increased the activities of phosphoenolpyruvate
      carboxykinase and glyoxysomal succinate oxidase and led to greater acid invertase
      activity during the aforementioned period. The expressions of both sucrose
      transporter (JrSUT1) and H+-ATPase (JrAHA1) genes especially in cotyledons and H+
      ATPase activity in kernels were significantly enhanced by exposure to cyanide.
      Thus in short-term HCN led to prevalence of carbohydrate catabolic events such as
      oxidative pentose phosphate pathway and possibly glycolysis in dormant walnut
      kernels. Long-term effects however, are increased gluconeogenesis and enhanced
      sugar transport capacity of kernels as a prerequisite for germination.

PMID- 27717455
TI  - Impact of anatomical traits of maize (Zea mays L.) leaf as affected by nitrogen
      supply and leaf age on bundle sheath conductance.
AB  - The mechanism of photosynthesis in C4 crops depends on the archetypal Kranz
      anatomy. To examine how the leaf anatomy, as altered by nitrogen supply and leaf
      age, affects the bundle sheath conductance (gbs), maize (Zea mays L.) plants were
      grown under three contrasting nitrogen levels. Combined gas exchange and
      chlorophyll fluorescence measurements were done on fully grown leaves at two leaf
      ages. The measured data were analysed using a biochemical model of C4
      photosynthesis to estimate gbs. The leaf microstructure and ultrastructure were
      quantified using images obtained from micro-computed tomography and microscopy.
      There was a strong positive correlation between gbs and leaf nitrogen content
      (LNC) while old leaves had lower gbs than young leaves. Leaf thickness, bundle
      sheath cell wall thickness and surface area of bundle sheath cells per unit leaf
      area (Sb) correlated well with gbs although they were not significantly affected
      by LNC. As a result, the increase of gbs with LNC was little explained by the
      alteration of leaf anatomy. In contrast, the combined effect of LNC and leaf age
      on Sb was responsible for differences in gbs between young leaves and old leaves.
      Future investigations should consider changes at the level of plasmodesmata and
      membranes along the CO2 leakage pathway to unravel LNC and age effects further.

PMID- 27717456
TI  - REPRESSOR OF ULTRAVIOLET-B PHOTOMORPHOGENESIS function allows efficient
      phototropin mediated ultraviolet-B phototropism in etiolated seedlings.
AB  - Ultraviolet B (UV-B) light is a part of the solar radiation which has significant
      effects on plant morphology, even at low doses. In Arabidopsis, many of these
      morphological changes have been attributed to a specific UV-B receptor, UV
      resistance locus 8 (UVR8). Recent findings showed that next to phototropin
      regulated phototropism, UVR8 mediated signaling is able of inducing directional
      bending towards UV-B light in etiolated seedlings of Arabidopsis, in a
      phototropin independent manner. In this study, kinetic analysis of phototropic
      bending was used to evaluate the relative contribution of each of these pathways
      in UV-B mediated phototropism. Diminishing UV-B light intensity favors the
      importance of phototropins. Molecular and genetic analyses suggest that UV-B is
      capable of inducing phototropin signaling relying on phototropin kinase activity
      and regulation of NPH3. Moreover, enhanced UVR8 responses in the UV-B
      hypersensitive rup1rup2 mutants interferes with the fast phototropin mediated
      phototropism. Together the data suggest that phototropins are the most important
      receptors for UV-B induced phototropism in etiolated seedlings, and a RUP
      mediated negative feedback pathway prevents UVR8 signaling to interfere with the
      phototropin dependent response.

PMID- 27717457
TI  - The Agrobacterium rhizogenes oncogenes rolB and ORF13 increase formation of
      generative shoots and induce dwarfism in Arabidopsis thaliana (L.) Heynh.
AB  - Plant transformation with the wild type Ri plasmid T-DNA of Agrobacterium
      rhizogenes is a promising method for breeding of compact plants and has been the
      subject of numerous studies. However, knowledge concerning the isolated functions
      of single genes and ORFs from the plasmid is limited. The rolB and ORF13
      oncogenes of A. rhizogenes show considerable promise in plant breeding, but have
      not been comprehensively studied. Detailed information regarding the
      morphological impact of specific genes of the Ri plasmid will allow for optimized
      targeted breeding of plants transformed with the wild type Ri plasmid T-DNA. rolB
      and ORF13 were recombined into the genome of Arabidopsis thaliana using
      Gateway(r) cloning and the effect on plant growth was assessed biometrically
      throughout the plants' life cycle. rolB-lines exhibited dwarfing, early necrosis
      of rosette leaves, altered leaf and flower morphology, and developed an increased
      number of inflorescences per rosette area compared to the wild type. ORF13-lines
      were extremely dwarfed, attaining only ca. 1% of the rosette area of the wild
      type, leaf and flower size was reduced, and the shape modified. The study
      documents that the traits inferred by the rolB oncogene yield plants with
      increased formation of generative shoots, but also result in some degree of
      premature senescence of vegetative organs. The extreme dwarfism seen in ORF13
      lines indicate that this oncogene may be more important in the dwarfing response
      of plants transformed with the wild type Ri plasmid T-DNA than previously assumed
      and that transformation with this oncogene induces a very compact phenotype.

PMID- 27717458
TI  - Genome wide association mapping of stripe rust resistance in Afghan wheat
      landraces.
AB  - Mining of new genetic resources is of paramount importance to combat the alarming
      spread of stripe rust disease and breakdown of major resistance genes in wheat.
      We conducted a genome wide association study on 352 un-utilized Afghan wheat
      landraces against stripe rust resistance in eight locations. High level of
      disease variation was observed among locations and a core-set of germplasm showed
      consistence performance. Linkage disequilibrium (LD) decayed rapidly (R2~0.16 at
      0cM) due to germplasm peerless diversity. The mixed linear model resulted in ten
      marker-trait associations (MTAs) across all environments representing five QTL.
      The extensively short LD blocks required us to repeat the analysis with less
      diverse subset of 220 landraces in which R2 decayed below 0.2 at 0.3cM. The
      subset GWAS resulted in 36 MTAs clustered in nine QTL. The subset analysis
      validated three QTL previously detected in the full list analysis. Overall, the
      study revealed that stripe rust epidemics in the geographical origin of this
      germplasm through time have permitted for selecting novel resistance loci.

PMID- 27717459
TI  - The down-regulation of the genes encoding Isoamylase 1 alters the starch
      composition of the durum wheat grain.
AB  - In rice, maize and barley, the lack of Isoamylase 1 activity materially affects
      the composition of endosperm starch. Here, the effect of this deficiency in durum
      wheat has been characterized, using transgenic lines in which Isa1 was knocked
      down via RNAi. Transcriptional profiling confirmed the partial down-regulation of
      Isa1 and revealed a pleiotropic effect on the level of transcription of genes
      encoding other isoamylases, pullulanase and sucrose synthase. The polysaccharide
      content of the transgenic endosperms was different from that of the wild type in
      a number of ways, including a reduction in the content of starch and a moderate
      enhancement of both phytoglycogen and beta-glucan. Some alterations were also
      induced in the distribution of amylopectin chain length and amylopectin fine
      structure. The amylopectin present in the transgenic endosperms was more readily
      hydrolyzable after a treatment with hydrochloric acid, which disrupted its semi
      crystalline structure. The conclusion was that in durum wheat, Isoamylase 1 is
      important for both the synthesis of amylopectin and for determining its internal
      structure.

PMID- 27717460
TI  - Cambial stem cells and their niche.
AB  - Unlike animals, plants often have an indefinite genetic potency to form new
      organs throughout their entire lifespan. Growth and organogenesis are driven by
      cell divisions in meristems at distinct sites within the plant. Since the
      meristems contributing to axial thickening in dicots (cambia) are separated from
      places where axes elongate (apical meristems); there is a need of communication
      to coordinate growth. In their behavior, some meristematic cells resemble animal
      stem cells whose daughter cells either maintain the capacity to divide over a
      long period of time or undergo differentiation. The behavior of stem cells is
      regulated by their microenvironment, the so called niche. The stem- and niche
      cell concept is now also widely accepted for apical meristems. An integral part
      of the cambial niche has recently been localized to the phloem. It steers cell
      division activity in the cambium via the release of a peptide signal and may be a
      hub to integrate signals from other stem cell populations to coordinate growth.
      Although these signals have yet to be determined, the discovery of the cambial
      niche cells will pave the way for a better understanding of inter-meristematic
      communication and cambial stem cell behavior.

PMID- 27717461
TI  - Genome-wide analysis of the Hsp70 family genes in pepper (Capsicum annuum L.) and
      functional identification of CaHsp70-2 involvement in heat stress.
AB  - Hsp70s function as molecular chaperones and are encoded by a multi-gene family
      whose members play a crucial role in plant response to stress conditions, and in
      plant growth and development. Pepper (Capsicum annuum L.) is an important
      vegetable crop whose genome has been sequenced. Nonetheless, no overall analysis
      of the Hsp70 gene family is reported in this crop plant to date. To assess the
      functionality of Capsicum annuum Hsp70 (CaHsp70) genes, pepper genome database
      was analyzed in this research. A total of 21 CaHsp70 genes were identified and
      their characteristics were also described. The promoter and transcript expression
      analysis revealed that CaHsp70s were involved in pepper growth and development,
      and heat stress response. Ectopic expression of a cytosolic gene, CaHsp70-2,
      regulated expression of stress-related genes and conferred increased
      thermotolerance in transgenic Arabidopsis. Taken together, our results provide
      the basis for further studied to dissect CaHsp70s' function in response to heat
      stress as well as other environmental stresses.

PMID- 27717462
TI  - Plastidic P2 glucose-6P dehydrogenase from poplar is modulated by thioredoxin m
      type: Distinct roles of cysteine residues in redox regulation and NADPH
      inhibition.
AB  - A cDNA coding for a plastidic P2-type G6PDH isoform from poplar (Populus tremula
      x tremuloides) has been used to express and purify to homogeneity the mature
      recombinant protein with a N-terminus His-tag. The study of the kinetic
      properties of the recombinant enzyme showed an in vitro redox sensing modulation
      exerted by reduced DTT. The interaction with thioredoxins (TRXs) was then
      investigated. Five cysteine to serine variants (C145S - C175S - C183S - C195S -
      C242S) and a variant with a double substitution for Cys175 and Cys183
      (C175S/C183S) have been generated, purified and biochemically characterized in
      order to investigate the specific role(s) of cysteines in terms of redox
      regulation and NADPH-dependent inhibition. Three cysteine residues (C145, C194,
      C242) are suggested to have a role in controlling the NADP+ access to the active
      site, and in stabilizing the NADPH regulatory binding site. Our results also
      indicate that the regulatory disulfide involves residues Cys175 and Cys183 in a
      position similar to those of chloroplastic P1-G6PDHs, but the modulation is
      exerted primarily by TRX m-type, in contrast to P1-G6PDH, which is regulated by
      TRX f. This unexpected specificity indicates differences in the mechanism of
      regulation, and redox sensing of plastidic P2-G6PDH compared to chloroplastic P1
      G6PDH in higher plants.

PMID- 27717463
TI  - A Raf-like MAPKKK gene, GhRaf19, negatively regulates tolerance to drought and
      salt and positively regulates resistance to cold stress by modulating reactive
      oxygen species in cotton.
AB  - Mitogen-activated protein kinase kinase kinases (MAPKKKs) function at the top
      level of MAPK cascades and play important roles in plant development and stress
      responses. Although MAPKKKs comprise the largest family in the MAPK cascades,
      very few Raf-like MAPKKKs have been functionally identified, especially in the
      economically important crop cotton. In this study, a Raf-like MAPKKK gene,
      GhRaf19, was characterized for the first time in cotton. Our data show that the
      expression of GhRaf19 was inhibited by PEG and NaCl and induced by cold (4
      degrees C) and H2O2. Furthermore, when GhRaf19 was silenced in cotton using virus
      induced gene silencing (VIGS), tolerance to drought and salt stress were
      enhanced, the accumulation of reactive oxygen species (ROS) was reduced, and ROS
      related gene expression was increased. Consistent with these results, in N.
      benthamiana, overexpressing-GhRaf19 reduced tolerance to drought and salt.
      However, GhRaf19-silenced plants showed lowered resistance to cold in cotton, and
      this effect was correlated with the accumulation of ROS. In contrast,
      overexpressing GhRaf19 in N. benthamiana increased resistance to cold by inducing
      higher levels of expression and activity of ROS-related antioxidant
      genes/enzymes. These results indicate that GhRaf19 negatively regulates tolerance
      to drought and salt and positively regulates resistance to cold stress by
      modulating cellular ROS in cotton.

PMID- 27717464
TI  - Nitric oxide is involved in stomatal development by modulating the expression of
      stomatal regulator genes in Arabidopsis.
AB  - As sessile organisms, plants require many flexible strategies to adapt to the
      environment. Although some environmental signaling pathways regulating stomatal
      development have been identified, how stomatal regulators are modulated by
      internal and external signals to determine the final stomatal abundance requires
      further exploration. In our studies, we found that nitric oxide (NO) promotes
      stomatal development with increased stomatal index as well as the relative number
      of meristemoids and guard mother cells [%(M+GMC)] in NO-treated wild-type
      Arabidopsis plants; this role of NO was further verified in the nox1 mutant,
      which exhibits higher NO levels, and the noa1 mutant, which exhibits low NO
      accumulation. To gain insight into the molecular mechanisms underlying the effect
      of NO, we further assayed the expression of genes involved in stomatal
      development and found that NO induces the expression of the master regulators
      SPCH, MUTE and SCRM2 to initiate stomatal development. In addition, MPK6 is also
      involved in NO-promoted stomatal development, as MPK6 expression was repressed in
      nox1 and NO-treated plants, and transgenic plants overexpressing MPK6 were less
      sensitive to SNP treatment in terms of changes in the%(M+GMC). Thus, our study
      shows that NO promotes the production of stomata by up-regulating the expression
      of SPCH, MUTE and SCRM2 and down-regulating MPK6 expression.

PMID- 27717466
TI  - Characterization of the Arabidopsis thaliana 2-Cys peroxiredoxin interactome.
AB  - Peroxiredoxins are ubiquitous thiol-dependent peroxidases for which chaperone and
      signaling roles have been reported in various types of organisms in recent years.
      In plants, the peroxidase function of the two typical plastidial 2-Cys
      peroxiredoxins (2-Cys PRX A and B) has been highlighted while the other
      functions, particularly in ROS-dependent signaling pathways, are still elusive
      notably due to the lack of knowledge of interacting partners. Using an ex vivo
      approach based on co-immunoprecipitation of leaf extracts from Arabidopsis
      thaliana wild-type and mutant plants lacking 2-Cys PRX expression followed by
      mass spectrometry-based proteomics, 158 proteins were found associated with 2-Cys
      PRXs. Already known partners like thioredoxin-related electron donors
      (Chloroplastic Drought-induced Stress Protein of 32kDa, Atypical Cysteine
      Histidine-rich Thioredoxin 2) and enzymes involved in chlorophyll synthesis
      (Protochlorophyllide OxidoReductase B) or carbon metabolism (Fructose-1,6
      BisPhosphatase) were identified, validating the relevance of the approach.
      Bioinformatic and bibliographic analyses allowed the functional classification of
      the identified proteins and revealed that more than 40% are localized in
      plastids. The possible roles of plant 2-Cys PRXs in redox signaling pathways are
      discussed in relation with the functions of the potential partners notably those
      involved in redox homeostasis, carbon and amino acid metabolisms as well as
      chlorophyll biosynthesis.

PMID- 27717465
TI  - Temporal and spatial expression and function of TaDlea3 in Triticum aestivum
      during developmental stages under drought stress.
AB  - Drought stress is a major factor limiting wheat growth and productivity. Late
      embryogenesis abundant (LEA) proteins are tolerant to water-related stress. To
      reveal the regulatory mechanisms of LEA proteins under drought stress, we cloned
      a novel group 3 LEA gene, namely, TaDlea3, from wheat (Triticum aestivum L.)
      Shaanhe 6. Subcellular localization assay showed that TaDlea3 protein accumulated
      in the cytoplasm. Quantitative real-time polymerase chain reaction results
      revealed that TaDlea3 expression was induced by drought stress. Western blot
      results indicated that TaDlea3 protein expression gradually increased with
      drought stress during four different developmental stages. Under normal
      conditions, no obvious phenotype difference was observed between the transgenic
      and wild-type seedlings. Meanwhile, the overexpression of TaDlea3 in Arabidopsis
      resulted in enhanced tolerance to drought stress, as determined by the assessment
      of antioxidant enzyme activities. Our results provide a basis for highly detailed
      functional analyses of LEA proteins and offer a promising approach for improving
      the tolerances of wheat cultivars to drought stress through genetic engineering.

PMID- 27717467
TI  - Induced plant-defenses suppress herbivore reproduction but also constrain
      predation of their offspring.
AB  - Inducible anti-herbivore defenses in plants are predominantly regulated by
      jasmonic acid (JA). On tomato plants, most genotypes of the herbivorous
      generalist spider mite Tetranychus urticae induce JA defenses and perform poorly
      on it, whereas the Solanaceae specialist Tetranychus evansi, who suppresses JA
      defenses, performs well on it. We asked to which extent these spider mites and
      the predatory mite Phytoseiulus longipes preying on these spider mites eggs are
      affected by induced JA-defenses. By artificially inducing the JA-response of the
      tomato JA-biosynthesis mutant def-1 using exogenous JA and isoleucine (Ile), we
      first established the relationship between endogenous JA-Ile-levels and the
      reproductive performance of spider mites. For both mite species we observed that
      they produced more eggs when levels of JA-Ile were low. Subsequently, we allowed
      predatory mites to prey on spider mite-eggs derived from wild-type tomato plants,
      def-1 and JA-Ile-treated def-1 and observed that they preferred, and consumed
      more, eggs produced on tomato plants with weak JA defenses. However, predatory
      mite oviposition was similar across treatments. Our results show that induced JA
      responses negatively affect spider mite performance, but positively affect the
      survival of their offspring by constraining egg-predation.

PMID- 27717469
TI  - De novo transcriptome assembly and identification of the gene conferring a
      "pandan-like" aroma in coconut (Cocos nucifera L.).
AB  - Thailand's aromatic coconut (Cocos nucifera L.) is a special type of green dwarf
      coconut, the liquid endosperm of which is characterized by a pleasant "pandan
      like" aroma due to the presence of 2-acetyl-1-pyrroline (2AP). The aim of this
      study was to perform a de novo assembly of transriptome from C. nucifera
      endosperm and to identify the gene responsible for 2AP biosynthesis. CnAMADH2 was
      identified as an ortholog of the rice aromatic gene and a G-to-C substitution
      found in exon 14 was associated with 2AP content in the aromatic green dwarf
      coconut accessions. The base substitution caused an amino-acid change, alanine-to
      proline, at position 442 (P442A). The presence of P at this position might alter
      the steric conformation at the loop region and subsequently result in an
      unstabilized dimer conformation that could lower AMADH enzyme activity. Among
      AMADH/BADH protein sequences in different plant species, the P442A mutation was
      found exclusively in aromatic coconut. The PCR marker developed based on this
      sequence variation can perfectly detect the aromatic and non-aromatic alleles of
      the gene. This study confirms the hypothesis that plants may share a mechanism of
      2AP biosynthesis. This is the first identification of the gene associated with
      2AP biosynthesis in a tree plant.

PMID- 27717468
TI  - Expression of a grape (Vitis vinifera) bZIP transcription factor, VlbZIP36, in
      Arabidopsis thaliana confers tolerance of drought stress during seed germination
      and seedling establishment.
AB  - Drought is one of the most serious factors that limit agricultural productivity
      and there is considerable interest in understanding the molecular bases of
      drought responses and their regulation. While numbers of basic leucine zipper
      (bZIP) transcription factors (TFs) are known to play key roles in response of
      plants to various abiotic stresses, only a few group K bZIP TFs have been
      functionally characterized in the context of stress signaling. In this study, we
      characterized the expression of the grape (Vitis vinifera) group K bZIP gene,
      VlbZIP36, and found evidence for its involvement in response to drought and the
      stress-associated phytohormone abscisic acid (ABA). Transgenic Arabidopsis
      thaliana lines over-expressing VlbZIP36 under the control of a constitutive
      promoter showed enhanced dehydration tolerance during the seed germination stage,
      as well as in the seedling and mature plant stages. The results indicated that
      VlbZIP36 plays a role in drought tolerance by improving the water status, through
      limiting water loss, and mitigating cellular damage. The latter was evidenced by
      reduced cell death, lower electrolyte leakage in the transgenic plants, as well
      as by increased activities of antioxidant enzymes. We concluded that VlbZIP36
      enhances drought tolerance through the transcriptional regulation of ABA-/stress
      related genes.

PMID- 27717470
TI  - Seed maturation: Simplification of control networks in plants.
AB  - Networks controlling developmental or metabolic processes in plants are often
      complex as a consequence of the duplication and specialisation of the regulatory
      genes as well as the numerous levels of transcriptional and post-transcriptional
      controls added during evolution. Networks serve to accommodate multicellular
      complexity and increase robustness to environmental changes. Mathematical
      simplification by regrouping genes or pathways in a limited number of hubs has
      facilitated the construction of models for complex traits. In a complementary
      approach, a biological simplification can be achieved by using genetic
      modification to understand the core and singular ancestral function of the
      network, which is likely to be more prevalent within the plant kingdom rather
      than specific to a species. With this viewpoint, we review examples of
      simplification successfully undertaken in yeast and other organisms. A strategy
      of progressive complementation of single, double and triple mutants of seed
      maturation confirmed the fundamental role of the AFL sub-family of B3
      transcription factors as master regulators of seed maturation, illustrating that
      biological simplification of complex networks could be more widely applied in
      plants. Defining minimal control networks will facilitate evolutionary
      comparisons of regulatory processes and the identification of an essential gene
      set for synthetic biology.

PMID- 27717471
TI  - Genetic variability of the phloem sap metabolite content of maize (Zea mays L.)
      during the kernel-filling period.
AB  - Using a metabolomic approach, we have quantified the metabolite composition of
      the phloem sap exudate of seventeen European and American lines of maize that had
      been previously classified into five main groups on the basis of molecular marker
      polymorphisms. In addition to sucrose, glutamate and aspartate, which are
      abundant in the phloem sap of many plant species, large quantities of aconitate
      and alanine were also found in the phloem sap exudates of maize. Genetic
      variability of the phloem sap composition was observed in the different maize
      lines, although there was no obvious relationship between the phloem sap
      composition and the five previously classified groups. However, following
      hierarchical clustering analysis there was a clear relationship between two of
      the subclusters of lines defined on the basis of the composition of the phloem
      sap exudate and the earliness of silking date. A comparison between the
      metabolite contents of the ear leaves and the phloem sap exudates of each
      genotype, revealed that the relative content of most of the carbon- and nitrogen
      containing metabolites was similar. Correlation studies performed between the
      metabolite content of the phloem sap exudates and yield-related traits also
      revealed that for some carbohydrates such as arabitol and sucrose there was a
      negative or positive correlation with kernel yield and kernel weight
      respectively. A posititive correlation was also found between kernel number and
      soluble histidine.

PMID- 27717472
TI  - The coordinated regulation of Na+ and K+ in Hordeum brevisubulatum responding to
      time of salt stress.
AB  - Hordeum brevisubulatum, called as wild barley, is a useful monocotyledonous
      halophyte for soil improvement in northern China. Although previously studied,
      its main salt tolerance mechanism remained controversial. The current work showed
      that shoot Na+ concentration was increased rapidly with stress time and
      significantly higher than in wheat during 0-168h of 100mM NaCl treatment. Similar
      results were also found under 25 and 50mM NaCl treatments. Even K+ was increased
      from 0.01 to 50mM in the cultural solution, no significant effect was found on
      tissue Na+ concentrations. Interestingly, shoot growth was improved, and stronger
      root activity was maintained in H. brevisubulatum compared with wheat after 7days
      treatment of 100mM NaCl. To investigate the long-term stress impact on tissue
      Na+, 100mM NaCl was prolonged to 60 days. The maximum values of Na+
      concentrations were observed at 7th in shoot and 14th day in roots, respectively,
      and then decreased gradually. Micro-electrode ion flux estimation was used and it
      was found that increasing Na+ efflux while maintaining K+ influx were the major
      strategies to reduce the Na+ concentration during long-term salt stress.
      Moreover, leaf Na+ secretions showed little contribution to the tissue Na+
      decrease. Thereby, the physiological mechanism for H. brevisubulatum to survive
      from long-term salt stress was proposed that rapid Na+ accumulation occurred in
      the shoot to respond the initial salt shock, then Na+ efflux was triggered and K+
      influx was activated to maintain a stable K+/Na+ ratio in tissues.

PMID- 27717473
TI  - Spatial differences in (Z)-3-hexen-1-ol production preferentially reduces
      Spodoptera litura larva attack on the young leaves of Nicotiana benthamiana.
AB  - Plants synthesize specialized metabolites which possess extremely important
      ecological functions including direct defense, indirect defense, and signaling.
      The optimal defense theory (ODT) proposes that defensive metabolites are
      preferentially allocated to the tissues with high fitness value or in locations
      that are easily injured. In our present study, using the model plant Nicotiana
      benthamiana, we found that direct defense of N. benthamiana against Spodoptera
      litura (Fabricius) larvae showed spatial differences in the sites producing
      defensive chemicals. The upper leaves possessed significantly stronger direct
      defense ability than the middle and lower leaves. Interestingly, the strong
      defense ability of the upper leaves was not due to occurrences of well-known
      defensive metabolites such as nicotine and chlorogenic acid. After damage, the
      middle and lower leaves emitted higher amounts of (Z)-3-hexen-1-ol than the upper
      leaves, which could both attract larvae and significantly increase the amount of
      middle and lower leaf eaten by the larvae. The spatial difference in (Z)-3-hexen
      1-ol emission may be due to spatial differences in expression of lipoxygenase
      (NbLOX2), which is responsible for the formation and emission of (Z)-3-hexen-1
      ol. This study provided new insight into ODT, showing that plants effectively
      protect easily injured tissues through reduction in concentration of herbivore
      feeding stimulant in the tissues.

PMID- 27717474
TI  - Genome-wide development and deployment of informative intron-spanning and intron
      length polymorphism markers for genomics-assisted breeding applications in
      chickpea.
AB  - The discovery and large-scale genotyping of informative gene-based markers is
      essential for rapid delineation of genes/QTLs governing stress tolerance and
      yield component traits in order to drive genetic enhancement in chickpea. A
      genome-wide 119169 and 110491 ISM (intron-spanning markers) from 23129 desi and
      20386 kabuli protein-coding genes and 7454 in silico InDel (insertion-deletion)
      (1-45-bp)-based ILP (intron-length polymorphism) markers from 3283 genes were
      developed that were structurally and functionally annotated on eight chromosomes
      and unanchored scaffolds of chickpea. A much higher amplification efficiency
      (83%) and intra-specific polymorphic potential (86%) detected by these markers
      than that of other sequence-based genetic markers among desi and kabuli chickpea
      accessions was apparent even by a cost-effective agarose gel-based assay. The
      genome-wide physically mapped 1718 ILP markers assayed a wider level of
      functional genetic diversity (19-81%) and well-defined phylogenetics among
      domesticated chickpea accessions. The gene-derived 1424 ILP markers were anchored
      on a high-density (inter-marker distance: 0.65cM) desi intra-specific genetic
      linkage map/functional transcript map (ICC 4958*ICC 2263) of chickpea. This
      reference genetic map identified six major genomic regions harbouring six robust
      QTLs mapped on five chromosomes, which explained 11-23% seed weight trait
      variation (7.6-10.5 LOD) in chickpea. The integration of high-resolution QTL
      mapping with differential expression profiling detected six including one
      potential serine carboxypeptidase gene with ILP markers (linked tightly to the
      major seed weight QTLs) exhibiting seed-specific expression as well as pronounced
      up-regulation especially in seeds of high (ICC 4958) as compared to low (ICC
      2263) seed weight mapping parental accessions. The marker information generated
      in the present study was made publicly accessible through a user-friendly web
      resource, "Chickpea ISM-ILP Marker Database". The designing of multiple ISM and
      ILP markers (2-5 markers/gene) from an individual gene (transcription factor)
      with numerous aforementioned desirable genetic attributes can widen the user
      preference to select suitable primer combination for simultaneous large-scale
      assaying of functional allelic variation, natural allelic diversity, molecular
      mapping and expression profiling of genes among chickpea accessions. This will
      essentially accelerate the identification of functionally relevant molecular tags
      regulating vital agronomic traits for genomics-assisted crop improvement by
      optimal resource expenses in chickpea.

PMID- 27717475
TI  - Identification of stable QTLs for seed oil content by combined linkage and
      association mapping in Brassica napus.
AB  - Seed oil content is an important agricultural trait in rapeseed breeding.
      Although numerous quantitative trait locus (QTL) have been identified, most of
      them cannot be applied in practical breeding mainly due to environmental
      instability or large confidence intervals. The purpose of this study was to
      identify and validate high quality and more stable QTLs by combining linkage
      mapping and genome-wide association study (GWAS). For linkage mapping, we
      constructed two F2 populations from crosses of high-oil content (~50%) lines
      6F313 and 61616 with a low-oil content (~40%) line 51070. Two high density
      linkage maps spanned 1987cM (1659 bins) and 1856cM (1746 bins), respectively. For
      GWAS, we developed more than 34,000 high-quality SNP markers based on 227
      accessions. Finally, 40 QTLs and 29 associations were established by linkage and
      association mapping in different environments. After merging the results, 32
      consensus QTLs were obtained and 7 of them were identified by both mapping
      methods. Seven overlapping QTLs covered an average confidence interval of 183kb
      and explained the phenotypic variation of 10.23 to 24.45%. We further developed
      allele-specific PCR primers to identify each of the seven QTLs. These stable QTLs
      should be useful in gene cloning and practical breeding application.

PMID- 27717476
TI  - The Cholodny-Went theory does not explain hydrotropism.
AB  - Optimization of water foraging by plants is partially achieved by the ability of
      roots to direct growth towards high water potential, a phenomenon termed
      hydrotropism. In contrast to gravitropism and phototropism, which require auxin
      redistribution, as suggested by the Cholodny-Went theory, hydrotropism is not
      mediated by the phytohormone auxin, which raises questions about the mechanism
      underlying this tropic response. Here we specify the open questions in this field
      of research and discuss the possible interactions of abscisic acid, calcium and
      reactive oxygen species as part of a dynamic system of sensing water potential in
      the root tip, transmission of the signal to the root elongation zone and
      promoting root curvature towards water. We conclude that root hydrotropism is
      mediated by inter-cellular signals that are not explained by the Cholodny-Went
      theory.

PMID- 27717477
TI  - Sunflower HaGPAT9-1 is the predominant GPAT during seed development.
AB  - In oil crops, triacylglycerol biosynthesis is an important metabolic pathway in
      which glycerol-3-phosphate acyltransferase (GPAT) performs the first acylation
      step. Mass spectrometry analysis of developing sunflower (Helianthus annuus) seed
      membrane fractions identified an abundant GPAT, HaGPAT9 isoform 1, with a N
      terminal peptide that possessed two phosphorylated residues with possible
      regulatory function. HaGPAT9-1 belongs to a broad eukaryotic GPAT family, similar
      to mammalian GPAT3, and it represents one of the two sunflower GPAT9 isoforms,
      sharing 90% identity with HaGPAT9-2. Both sunflower genes are expressed during
      seed development and in vegetative tissues, with HaGPAT9-1 transcripts
      accumulating at relatively higher levels than those for HaGPAT9-2. Green
      fluorescent protein tagging of HaGPAT9-1 confirmed its subcellular accumulation
      in the endoplasmic reticulum. Despite their overall sequence similarities, the
      two sunflower isoforms displayed significant differences in their enzymatic
      activities. For instance, HaGPAT9-1 possesses in vivo GPAT activity that rescues
      the lethal phenotype of the cmy228 yeast strain, while in vitro assays revealed a
      preference of HaGPAT9-1 for palmitoyl-, oleoyl- and linoleoyl-CoAs of one order
      of magnitude, with the highest increase in yield for oleoyl- and linoleoyl-CoAs.
      By contrast, no enzymatic activity could be detected for HaGPAT9-2, even though
      its over-expression modified the TAG profile of yeast.

PMID- 27717478
TI  - Physiological adjustments of a Mediterranean shrub to long-term experimental
      warming and drought treatments.
AB  - Warmer temperatures and extended drought in the Mediterranean Basin are becoming
      increasingly important in determining plant physiological processes and affecting
      the regional carbon budget. The responses of plant physiological variables such
      as shoot water potential (Psi), carbon-assimilation rates (A), stomatal
      conductance (gs) and intrinsic water-use efficiency (iWUE) to these climatic
      regimes, however, are not well understood. We conducted long-term (16 years)
      field experiments with mild nocturnal warming (+0.6 degrees C) and drought (-20%
      soil moisture) in a Mediterranean early-successional shrubland. Warming treatment
      moderately influenced Psi, A and gs throughout the sampling periods, whereas
      drought treatment strongly influenced these variables, especially during the
      summer. The combination of a natural drought in summer 2003 and the treatments
      significantly decreased A and iWUE. Foliar delta13C increased in the treatments
      relative to control, but not significantly. The values of Psi, A and gs were
      correlated negatively with vapor-pressure deficit (VPD) and positively with soil
      moisture and tended to be more dependent on the availability of soil water. The
      plant, however, also improved the acclimation to drier and hotter conditions by
      physiological adjustments (gs and iWUE). Understanding these physiological
      processes in Mediterranean shrubs is crucial for assessing further climate change
      impacts on ecosystemic functions and services.

PMID- 27717479
TI  - Mesophyll conductance and reaction-diffusion models for CO2 transport in C3
      leaves; needs, opportunities and challenges.
AB  - One way to increase potential crop yield could be increasing mesophyll
      conductance gm. This variable determines the difference between the CO2 partial
      pressure in the intercellular air spaces (Ci) and that near Rubisco (Cc). Various
      methods can determine gm from gas exchange measurements, often combined with
      measurements of chlorophyll fluorescence or carbon isotope discrimination. gm
      lumps all biochemical and physical factors that cause the difference between Cc
      and Ci. gm appears to vary with Ci. This variability indicates that gm does not
      satisfy the physical definition of a conductance according to Fick's first law
      and is thus an apparent parameter. Uncertainty about the mechanisms that
      determine gm can be limited to some extent by using analytical models that
      partition gm into separate conductances. Such models are still only capable of
      describing the CO2 diffusion pathway to a limited extent, as they make implicit
      assumptions about the position of mitochondria in the cells, which affect the re
      assimilation of (photo)respired CO2. Alternatively, reaction-diffusion models may
      be used. Rather than quantifying gm, these models explicitly account for factors
      that affect the efficiency of CO2 transport in the mesophyll. These models
      provide a better mechanistic description of the CO2 diffusion pathways than
      mesophyll conductance models. Therefore, we argue that reaction-diffusion models
      should be used as an alternative to mesophyll conductance models, in case the aim
      of such a study is to identify traits that can be improved to increase gm.

PMID- 27717480
TI  - Soybean proteins GmTic110 and GmPsbP are crucial for chloroplast development and
      function.
AB  - We have identified a viable-yellow and a lethal-yellow chlorophyll-deficient
      mutant in soybean. Segregation patterns suggested single-gene recessive
      inheritance for each mutant. The viable- and lethal-yellow plants showed
      significant reduction of chlorophyll a and b. Photochemical energy conversion
      efficiency and photochemical reflectance index were reduced in the viable-yellow
      plants relative to the wildtype, whereas the lethal-yellow plants showed no
      electron transport activity. The viable-yellow plants displayed reduced thylakoid
      stacking, while the lethal-yellow plants exhibited failure of proplastid
      differentiation into normal chloroplasts with grana. Genetic analysis revealed
      recessive epistatic interaction between the viable- and the lethal-yellow genes.
      The viable-yellow gene was mapped to a 58kb region on chromosome 2 that contained
      seven predicted genes. A frame shift mutation, due to a single base deletion in
      Glyma.02g233700, resulted in an early stop codon. Glyma.02g233700 encodes a
      translocon in the inner membrane of chloroplast (GmTic110) that plays a critical
      role in plastid biogenesis. The lethal-yellow gene was mapped to an 83kb region
      on chromosome 3 that contained 13 predicted genes. Based on the annotated
      functions, we sequenced three potential candidate genes. A single base insertion
      in the second exon of Glyma.03G230300 resulted in a truncated protein.
      Glyma.03G230300 encodes for GmPsbP, an extrinsic protein of Photosystem II that
      is critical for oxygen evolution during photosynthesis. GmTic110 and GmPsbP
      displayed highly reduced expression in the viable- and lethal-yellow mutants,
      respectively. The yellow phenotypes in the viable- and lethal-yellow mutants were
      due to the loss of function of GmTic110 or GmPsbP resulting in photooxidative
      stress.

PMID- 27717482
TI  - Corrigendum to "Urokinase plasminogen activator receptor and its soluble form in
      common biopsy-proven kidney diseases and in staging of diabetic nephropathy".

PMID- 27717483
TI  - Corrigendum to "Higgins V, Chan MK, Nieuwesteeg M, Hoffman BR, Bromberg IL,
      Gornall D, Randell E, Adeli K. Transference of CALIPER pediatric reference
      intervals to biochemical assays on the Roche Cobas 6000 and the Roche Modular P."
      [Clin. Biochem. 2016 49(1):139-49].

PMID- 27717481
TI  - Abiotic stress upregulated TaZFP34 represses the expression of type-B response
      regulator and SHY2 genes and enhances root to shoot ratio in wheat.
AB  - Q-type C2H2 zinc finger proteins (ZFPs) are plant-specific DNA-binding proteins
      containing a conserved QALGGH motif. This study investigated the function of
      abiotic stress-inducible and predominantly root-expressed Triticum aestivum ZFPs
      (TaZFP22, TaZFP34 and TaZFP46) with a focus on TaZFP34. Expression of TaZFP34 in
      roots was upregulated by high salinity, dehydration, oxidative and cold stresses.
      Overexpression of TaZFP34 in wheat roots resulted in an increased root-to-shoot
      ratio, a phenomenon observed during plant adaptation to drying soil. Expression
      of a number of genes which are potentially involved in modulating root growth was
      significantly altered in the roots of TaZFP34 overexpressing lines. In
      particular, the transcript levels of TaRR12B, TaRR12D and TaSHY2 that are
      homologues of known negative regulators of root growth were significantly
      reduced. Expression of shoot growth-related genes, such as GA3-ox and expansins,
      was downregulated in the transgenic shoots. TaZFP34 bound to (C/G)AGT(G/A)-like
      elements in the promoters of TaZFP34 down-regulated TaRR12D and TaSHY2 and
      transrepressed the reporter gene expression driven by TaRR12D and TaSHY2
      promoters. Expression of the above reporter genes was also repressed by TaZFP46
      and TaZFP22. These data suggest that TaZFP34 is a transcriptional repressor and
      is involved in modulating the root-to-shoot ratio.

PMID- 27717484
TI  - [New approaches to the treatment of respiratory failure: High flow therapy].

PMID- 27717486
TI  - Legionellosis in the occupational setting.
AB  - Legionellosis is the common name for two infections, Legionnaires' disease (LD)
      and Pontiac fever (PF), both caused by Legionella bacteria. Although with low
      incidence, LD is an important cause of community- and hospital-acquired
      pneumonia. Among community-acquired cases, an increasing number was reported to
      be linked to the occupational setting, posing the need for better recognition of
      work activities at risk of legionellosis. In this work, we selected and reviewed
      relevant literature on cases of occupational legionellosis published between 1978
      and 2016 in order to define the: i) etiology; ii) sources of infection, iii) work
      activities at risk, iv) infection rates, v) predisposing factors, vi) mortality
      and vii) country distribution. To our knowledge, this is the first review to
      provide an analysis of cases of occupational legionellosis. A literature search
      in the PubMed website was started on January 31, 2015 and ended on June 30, 2016.
      Cases of occupational legionellosis documented in the scientific literature were
      retrieved from PubMed upon interrogation with the following keywords: "Legionella
      pneumophila", "Legionnaires' disease", "Pontiac fever", and "legionellosis", in
      combination with "employees", "workers", and "occupational". Abstracts were
      reviewed, and applicable articles were obtained. Only articles that met the
      inclusion criteria were considered. Forty-seven articles were selected, reporting
      confirmed cases of legionellosis which occurred over 66 years (1949-2015), and
      involved 805 workers (221, LD; 584, PF). Fatalities were all associated with LD,
      resulting in 4.1% mortality. The most common etiologic agents were Legionella
      pneumophila (58.5%) and Legionella feeleii (39.4%), the latter being responsible
      for only one large outbreak of PF. Workplaces more frequently associated with
      occupational legionellosis were industrial settings (62.0%), office buildings
      (27.3%) and healthcare facilities (6.3%), though cases were also reported from a
      variety of workplaces, e.g. artesian excavation and horticultural sites, lorry
      parks, ships, water and sewage plants. With few exceptions, cases occurred in
      industrialized countries of the northern hemisphere. Overall, our review
      highlights an extended spectrum of occupational categories at risk for
      legionellosis. For all categories, infection originated from exposure to work
      generated aerosols contaminated with Legionella spp., and industrial facilities
      equipped with cooling towers or coolant systems were the most common occupational
      settings. These observations should raise awareness of the risk of acquiring
      legionellosis at work, and help to improve prevention and control measures for
      this infrequent but still problematic disease.

PMID- 27717488
TI  - Ten years since the discovery of iPS cells: The current state of their clinical
      application.
AB  - On the 10-year anniversary of the discovery of induced pluripotent stem cells, we
      review the main results from their various fields of application, the obstacles
      encountered during experimentation and the potential applications in clinical
      practice. The efficacy of induced pluripotent cells in clinical experimentation
      can be equated to that of human embryonic stem cells; however, unlike stem cells,
      induced pluripotent cells do not involve the severe ethical difficulties entailed
      by the need to destroy human embryos to obtain them. The finding of these cells,
      which was in its day a true scientific milestone worthy of a Nobel Prize in
      Medicine, is currently enveloped by light and shadow: high hopes for regenerative
      medicine versus the, as of yet, poorly controlled risks of unpredictable
      reactions, both in the processes of dedifferentiation and subsequent
      differentiation to the cell strains employed for therapeutic or experimentation
      goals.

PMID- 27717487
TI  - A survey to medical residents on the performance of diagnostic and therapeutic
      thoracenteses: a training gap?
AB  - OBJECTIVE: Pleural fluid aspiration is a routine procedure for pulmonologists and
      internists. Our aim was to evaluate technical and methodological aspects of
      diagnostic and therapeutic thoracenteses performed by last two-year residents of
      Pulmonology and Internal Medicine. METHODS: An online 24-item questionnaire was
      sent to participants, and responses were evaluated according to the medical
      specialty. RESULTS: The survey was completed by 139 (17.1%) residents (71
      internists and 68 pulmonologists). 29.5% and 41% performed one or no diagnostic
      or therapeutic thoracenteses monthly, respectively. Only 44% used ultrasonography
      to guide pleural procedures. Less than half of respondents used local anesthesia
      for diagnostic aspirations. Contrary to current recommendations, 25% of residents
      employed intramuscular needles for therapeutic aspirations. More than 80% of
      residents routinely ordered pleural fluid cultures and cytological studies,
      regardless of the clinical suspicion. About 40% requested imaging studies after a
      diagnostic thoracentesis. Half or more of the respondents were unaware of pH
      measurement methodologies, culture type for mycobacteria, and performance of cell
      blocks. Pulmonologists were more experienced than internists, and also made use
      of ultrasonography more frequently. CONCLUSION: This survey highlights gaps of
      knowledge and skills in conducting diagnostic and therapeutic thoracenteses.

PMID- 27717485
TI  - Different components of blood pressure are associated with increased risk of
      atherosclerotic cardiovascular disease versus heart failure in advanced chronic
      kidney disease.
AB  - Blood pressure is a modifiable risk for cardiovascular disease (CVD). Among
      hemodialysis patients, there is a U-shaped association between blood pressure and
      risk of death. However, few studies have examined the association between blood
      pressure and CVD in patients with stage 4 and 5 chronic kidney disease. Here we
      studied 1795 Chronic Renal Insufficiency Cohort (CRIC) Study participants with
      estimated glomerular filtration rate <30 ml/min per 1.73 m2 and not on dialysis.
      The association of systolic (SBP), diastolic (DBP), and pulse pressure with the
      risk of physician-adjudicated atherosclerotic CVD (stroke, myocardial infarction,
      or peripheral arterial disease) and heart failure was tested using Cox regression
      adjusted for demographics, comorbidity and medications. There was a significant
      association with higher SBP (adjusted hazard ratio 2.04 [95% confidence interval:
      1.46-2.84]) for SBP over 140 vs under 120 mmHg, higher DBP (2.52 [1.54-4.11]) for
      DBP >90 mm Hg versus <80 mm Hg and higher pulse pressure (2.67 [1.82-3.92]) for
      pulse pressure >68 mm Hg versus <51 mm Hg with atherosclerotic CVD. For heart
      failure, there was a significant association with higher pulse pressure only
      (1.42 [1.05-1.92]) for pulse pressure >68 mm Hg versus <51 mmHg, but not for SBP
      or DBP. Thus, among participants with stage 4 and 5 chronic kidney disease, there
      was an independent association between higher SBP, DBP, and pulse pressure with
      the risk of atherosclerotic CVD, whereas only higher pulse pressure was
      independently associated with a greater risk of heart failure. Further trials are
      needed to determine whether aggressive reduction of blood pressure decreases the
      risk of CVD events in patients with stage 4 and 5 chronic kidney disease.

PMID- 27717489
TI  - Comparison of Aurantii Fructus Immaturus and Aurantii Fructus based on multiple
      chromatographic analysis and chemometrics methods.
AB  - To get a better understanding of the bioactive constituents in Aurantii Fructus
      Immaturus (AFI) and Aurantii Fructus (AF), in the present study, a comprehensive
      strategy integrating multiple chromatographic analysis and chemometrics methods
      was firstly proposed. Based on segmental monitoring, a high-performance liquid
      chromatography (HPLC)-variable wavelength detection method was established for
      simultaneous quantification of ten major flavonoids, and the quantitative data
      were further analyzed by hierarchical cluster analysis (HCA) and principal
      component analysis (PCA). A strong cation exchange-high performance liquid
      chromatography (SCX-HPLC) method combined with t-test and one-way analysis of
      variance (ANOVA) was developed to determine synephrine, the major alkaloid in AFI
      and AF. The essential oils were analyzed by gas chromatography-mass spectrometry
      (GC-MS) and further processed by partial least squares discrimination analysis
      (PLS-DA). The results indicated that the contents of ten flavonoids and
      synephrine in AFI were significantly higher than those in AF, and significant
      difference existed in samples from different geographical origins. Also, 9
      differential volatile constituents detected could be used as chemical markers for
      discrimination of AFI and AF. Collectively, the proposed comprehensive analysis
      might be a well-acceptable strategy to evaluate the quality of traditional citrus
      herbs.

PMID- 27717491
TI  - Location-independent analysis of structural progression of osteoarthritis-Taking
      it all apart, and putting the puzzle back together makes the difference.
AB  - OBJECTIVE: The metric accepted by regulatory bodies for determining structural
      progression in clinical trials of knee osteoarthritis (OA) remains change in
      radiographic joint space width in the medial femorotibial compartment. However,
      magnetic resonance imaging has revealed that cartilage loss is spatially
      heterogeneous, and that it is enigmatic which knee will lose cartilage at which
      location. Whereas previous reviews have focused on imaging in general, the
      purpose of this particular perspective is to highlight availability and
      applications of location-independent analysis methodology in measuring structural
      progression in epidemiological and interventional clinical trials, and to
      highlight its specific advantages over existing methodologies. METHODS: Narrative
      review/perspective based on a Pubmed search of original articles from 2009 to
      current. RESULTS: Ordering longitudinal change in subregion cartilage thickness
      by magnitude and direction, and averaging such ordered values or sums of negative
      and positive changes across knees is shown to be superior in detecting risk
      factors and interventional effects on structural progression of knee OA. Further,
      the methodology permits exploration of cartilage loss and gain simultaneously,
      phenomena that are missed when measurements are confined to cartilage volume or
      thickness loss in plates or compartments. CONCLUSIONS: Given spatial
      heterogeneity of cartilage loss in knee OA, location-independent analysis by MRI
      may provide opportunity for a paradigm shift. The authors recommend use of a
      location-independent metrices as the structural endpoints in epidemiological and
      intervention trials, particularly when examining anabolic and catabolic drug
      effects. Location-independent methods may be translated to analysis of cartilage
      composition and other articular tissues.

PMID- 27717492
TI  - Ignoring da Vinci and Darwin: The making of a better outlet valve.

PMID- 27717490
TI  - Brain metastases in patients with EOC: Clinico-pathological and prognostic
      factors. A multicentric retrospective analysis from the MITO group (MITO 19).
AB  - BACKGROUND: Brain metastases (BM) from epithelial ovarian cancer (EOC) are
      considered a rare and unfavourable event. There is no consensus regarding the
      best management of these patients. METHODS: A multicenter retrospective analysis
      of patients with BM from EOC treated between 1997 and 2014 in 18 institutions of
      the MITO (Multicenter Italian Trials in Ovarian cancer) group was conducted.
      Univariate and multivariate analysis were performed. RESULTS: A total of 174
      women were identified as having BM from EOC. The median time interval between
      primary diagnosis of EOC and occurrence of BM was 26months (range 2-129months).
      The median overall survival from primary EOC diagnosis was 48months (95% CI 39.5
      56.4months) and from diagnosis of BM was 12months (95% CI 9.6-14.3months). The
      majority of enrolled women (81.7%) were classified as sensitive to platinum-based
      chemotherapy. Four variables were significantly associated with poor overall
      survival in multivariate analysis: multiple BM [HR: 1.86 (95% CI: 1.22-2.84)],
      presence of extracranial disease [HR: 1.77 (95% CI: 1.11-2.83)] age [HR: 1.74
      (95% CI: 1.17-2.59)], and monotherapy [HR: 2.57 (95% CI: 1.64-3.86)]. On the
      contrary, residual tumor at primary surgery, FIGO stage at primary diagnosis and
      platinum sensitivity were found to have no significant impact on survival from
      diagnosis of brain lesions. CONCLUSIONS: Our results suggest that BM is a rare
      and late manifestation of EOC, with a 12-month life-span expectation. Multiple
      approach is a positive independent prognostic factor and should be proposed to
      carefully selected patients.

PMID- 27717494
TI  - Aortic reconstruction for an infected stent graft with a composite homograft.

PMID- 27717493
TI  - Why don't things happen the same way every time?

PMID- 27717495
TI  - Intra-aortic balloon pump therapy negatively affects flow through a continuous
      flow left ventricular assist device.

PMID- 27717496
TI  - Preserving the V-engine shape of the left ventricle with Melody mitral valve
      replacement in small children.

PMID- 27717497
TI  - Promise and Limitations of Procalcitonin to Identify Bacterial Infections in the
      Pediatric Intensive Care Unit.

PMID- 27717498
TI  - Physical Activity and Its Correlates in Youth with Multiple Sclerosis.
AB  - OBJECTIVES: To investigate physical activity levels in youth with multiple
      sclerosis and monophasic acquired demyelinating syndromes ([mono-ADS], ie,
      children without relapsing disease) compared with healthy controls and to
      determine factors that contribute to engagement in physical activity. We
      hypothesized that greater physical activity goal setting and physical activity
      self-efficacy would be associated with greater levels of vigorous physical
      activity in youth with multiple sclerosis. STUDY DESIGN: A total of 68
      consecutive patients (27 multiple sclerosis, 41 mono-ADS) and 37 healthy controls
      completed fatigue, depression, Physical Activity Self-Efficacy Scale, perceived
      disability, Exercise Goal-Setting scale, and physical activity questionnaires,
      and wore an accelerometer for 7 days. All patients had no ambulatory limitations
      (Expanded Disability Status Scale, scores all <4). RESULTS: Youth with multiple
      sclerosis engaged in fewer minutes per day of vigorous (P = .009) and moderate
      and vigorous physical activity (P = .048) than did patients with mono-ADS and
      healthy controls. A lower proportion of the group with multiple sclerosis (63%)
      reported participating in any strenuous physical activity than the mono-ADS (85%)
      and healthy control (89%) groups (P = .020). When we adjusted for age and sex,
      the Physical Activity Self-Efficacy Scale and Exercise Goal-Setting scale were
      associated positively with vigorous physical activity in the group with multiple
      sclerosis. Fatigue and depression did not predict physical activity or
      accelerometry metrics. CONCLUSIONS: Youth with multiple sclerosis participate in
      less physical activity than their counterparts with mono-ADS and healthy
      controls. Physical activity self-efficacy and exercise goal setting serve as
      potentially modifiable correlates of physical activity, and are measures suited
      to future interventions aimed to increase physical activity in youth with
      multiple sclerosis.

PMID- 27717499
TI  - [Pediatric ependymomas: Current diagnosis and therapy].
AB  - Ependymomas represent 10% of pediatric brain tumors. In the recent WHO 2016
      classification, pathology is enriched by localization and molecular biology.
      Whatever the age, total removal by one or several looks when required remains a
      major prognostic factor. In children, focal radiation remains a standard, while
      the role of chemotherapy is matter of randomized studies. In infants, front line
      chemotherapy is the standard. Inclusion in the SIOP ependymoma II protocol is
      encouraged. In case of relapse, further surgery and radiation are advised, while
      inclusion in innovative trials including re-irradiation, and phase I-II should be
      encouraged. A better understanding of underlying mechanisms of ependymoma cell
      will provide in the close future, the key to use targeted therapies at time of
      relapse, and very soon as first line therapy for some subgroups of patients.

PMID- 27717500
TI  - Vasculitis induced by phenobarbital with cross-reactivity to carbamazepine.

PMID- 27717501
TI  - Cuticular hydrocarbons and sucrose esters as chemotaxonomic markers of wild and
      cultivated tomato species (Solanum section Lycopersicon).
AB  - The tomato (Solanum lycopersicum L.) is one of the most important vegetables
      worldwide. Due to the limited genetic variability, wild related species are
      considered as potential gene pool for breeding cultivated plants with enriched
      genetic basis. Taxonomic relations between tomato species at the level of single
      groups and taxa still remain, however, not fully resolved. Hence, in addition to
      already reported classification based on the morphology of the plants and
      molecular markers, we proposed chemotaxonomic approach to unveil some aspects of
      tomato taxonomy. Cuticular hydrocarbons and surface sucrose esters (SEs) were
      used as chemotaxonomic markers. Classification based on the cuticular hydrocarbon
      profile was in good agreement with other taxonomic studies as long as between
      species differences were taken into account. Clear separation of the common
      tomato and closely related species from the majority of S. pennellii accessions
      was obtained. In the same time, however, S. pennellii revealed broad variation:
      based on the results, three highly distinct types of these plants were proposed,
      among them one type was very similar to cultivated tomato and its relatives.
      Addition of SEs profiles to the dataset did not impair the classification, but
      clarified the position of S. pennellii. The results suggest possible hybrid
      origin of some of S. pennellii and wild S. lycopersicum accessions, and the
      approach proposed has a potential to identify such hybrid plant lines.

PMID- 27717502
TI  - Single-center experience of stent retriever thrombectomy in acute ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Recently, positive data from several randomized
      controlled trials (RCTs) of endovascular therapy for acute ischemic stroke (AIS)
      has emerged. The aim of this retrospective study is to present our clinical
      experience in cerebral vessel occlusion treatment using retrievable intracranial
      stents. METHODS: Forty-three consecutive patients with ischemic stroke (median
      age 75, range 22-87) treated by stent retriever thrombectomy (SolitaireTM FR)
      between January 2013 and December 2015 were identified. We retrospectively
      assessed Thrombolysis in Cerebral Infarction (TICI) scale (2b-3 considered as
      successful recanalization), clinical outcome using modified Rankin scale (mRs) at
      3 months (regarding score 0-2 as good clinical outcome), device-related
      complications and symptomatic intracranial hemorrhage (sICH; parenchymal hematoma
      Type 1 or 2 and National Institutes of Health Stroke Scale [NIHSS] score
      increment >=4 points) rate. RESULTS: The mean NIHSS score on admission was 16.4
      (median 16). The mean time from onset to groin puncture (time to treatment) was
      290min (median 254min). Successful recanalization was achieved in 30 (69.8%)
      cases. The mean time from onset to successful reperfusion or procedure
      termination (time to reperfusion) was 394min (median 375min). Good outcome was
      observed in 17 (39.5%) patients and mortality was 27.9% (n=12). We found 2 (4,7%)
      sICHs, one (2,3%) thromboembolic event in different vascular territory and one
      (2,3%) groin hematoma. CONCLUSION: Stent retriever thrombectomy for the treatment
      of ischemic stroke is safe, provides high rate of recanalization and good
      clinical outcomes in the setting of large vessel occlusion.

PMID- 27717504
TI  - Abdominal wall abscess secondary to colonoscopic polypectomy. Radiological
      management.

PMID- 27717503
TI  - BTLA-expressing CD11c antigen presenting cells in patients with active
      tuberculosis exhibit low capacity to stimulate T cell proliferation.
AB  - Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated
      negative regulation of T cell activation, the role of BTLA in antigen presenting
      cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly
      understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in
      patients with ATB. Particularly, BTLA expression in CD11c APCs was likely
      associated with the attenuated stimulatory capacity on T cells (especially CD8+ T
      cell) proliferation. BTLA-expressing CD11c APCs showed lower antigen uptake
      capacity, lower CD86 expression, higher HLA-DR expression, and enhanced IL-6
      secretion, compared to counterpart BTLA negative CD11c APCs in healthy controls
      (HC). Interestingly, BTLA-expressing CD11c APCs from ATB patients displayed lower
      expression of HLA-DR and less IL-6 secretion, but higher expression of CD86 than
      those from HC volunteers. Mixed lymphocyte reaction suggests that BTLA expression
      is likely associated with positive rather than conventional negative regulation
      of CD11c APCs stimulatory capacity. This role is impaired in ATB patients
      manifested by low expression of HLA-DR and low production of IL-6. This previous
      unappreciated role for BTLA may have implications in the prevention and treatment
      of patients with ATB.

PMID- 27717505
TI  - Emerging Field of Cardiomics: High-Throughput Investigations into Transcriptional
      Regulation of Cardiovascular Development and Disease.
AB  - Congenital heart defects remain a leading cause of infant mortality in the
      western world, despite decades of research focusing on cardiovascular development
      and disease. With the recent emergence of several high-throughput technologies
      including RNA sequencing, chromatin-immunoprecipitation-coupled sequencing, mass
      spectrometry-based proteomics analyses, and the numerous variations of these
      strategies, investigations into cardiac development have been transformed from
      candidate-based studies into whole-genome, -transcriptome, and -proteome
      undertakings. In this review, we discuss several reports that have emerged from
      our laboratory and others over the past 5 years that emphasize the versatility of
      large dataset-based investigations of cardiogenic transcription factors, from
      phenotypic validations and new gene implications to the identification of novel
      roles of well-studied transcriptional regulators.

PMID- 27717507
TI  - EGFR as a Pharmacological Target in EGFR-Mutant Non-Small-Cell Lung Cancer: Where
      Do We Stand Now?
AB  - Targeting the epidermal growth factor receptor (EGFR) using tyrosine kinase
      inhibitors (TKIs) is highly effective in terms of tumor response rate, survival,
      and quality of life. However, acquired resistance to EGFR-TKIs is inevitable.
      Ongoing clinical trials will provide evidence for optimal strategies for patients
      with EGFR mutant non-small-cell lung cancer (NSCLC) in the near future. Numerous
      new agents are specifically addressing resistance mechanisms; mature data are
      related to the T790M mutation and MET pathway activation. Here, we provide a
      comprehensive review of new perspectives on how to optimize the management of
      this molecular disease.

PMID- 27717508
TI  - Rare anatomical variation of the brachiocephalic trunk encountered in
      tracheostomy.
AB  - Tracheostomy is a common procedure in head and neck surgery and emergency
      medicine to secure a patent airway. Surgeons should always be aware of anatomical
      variants of the branches of the aortic arch, which could lead to life-threatening
      complications. Open tracheostomy is the safest emergency procedure.

PMID- 27717506
TI  - The CRF System as a Therapeutic Target for Neuropsychiatric Disorders.
AB  - The major neuropsychiatric disorders are devastating illnesses that are only
      modestly responsive to treatment. Improving the treatment of these conditions
      will require innovative new strategies that depart from previously focused-on
      pharmacological mechanisms. Considerable preclinical and clinical data indicate
      corticotropin-releasing factor (CRF) signaling as a target for new psychotropic
      drug development. Here we review alterations in the CRF system reported in
      several psychiatric conditions. We also examine the preclinical work that has
      dissected the distinctive roles of CRF receptors in specific circuits relevant to
      these disorders. We further describe the clinical trials of CRF1 receptor
      antagonists that have been conducted. Although these clinical trials have thus
      far met with limited therapeutic success, the unfolding complexity of the CRF
      system promises many future directions for studying its role in the etiology and
      treatment of neuropsychiatric conditions.

PMID- 27717510
TI  - Mapping current research trends on anterior cruciate ligament injury risk against
      the existing evidence: In vivo biomechanical risk factors - A Letter to the
      Editor.

PMID- 27717509
TI  - Patterns of palliative care service consultation in a sample of critically ill
      ICU patients at high risk of dying.
AB  - OBJECTIVE: Describe patterns of palliative care service consultation among a
      sample of ICU patients at high risk of dying. BACKGROUND: Patients receiving
      mechanical ventilation (MV) face threats to comfort, social connectedness and
      dignity due to pain, heavy sedation and physical restraint. Palliative care
      consultation services may mitigate poor outcomes. METHODS: From a dataset of 1440
      ICU patients with >=2 days of MV and >=12 h of sustained wakefulness, we
      identified those at high risk of dying and/or who died and assessed patterns of
      sub-specialty palliative care consultation. RESULTS: About half (773/1440 [54%])
      were at high risk of dying or died, 73 (9.4%) of whom received palliative care
      consultation. On average, referral occurred after 62% of the ICU stay had
      elapsed. Primary reason for consult was clarification of goals of care (52/73
      [72.2%]). CONCLUSIONS: Among MV ICU patients at high risk of dying, palliative
      care service consultation occurs late and infrequently, suggesting a role for
      earlier palliative care.

PMID- 27717512
TI  - Reply to Dr. Lacrosse et al.

PMID- 27717511
TI  - Patient preferences regarding prophylactic cranial irradiation: A discrete choice
      experiment.
AB  - INTRODUCTION: In patients with non-small cell lung cancer (NSCLC) treated with
      chemoradiotherapy (CRT), prophylactic cranial irradiation (PCI) is not standard
      practice. This study determined patient preferences for PCI with respect to
      survival benefit, reduction in brain metastases (BM) and acceptable toxicity.
      METHODS: A Discrete Choice Experiment was completed pre- and post-treatment.
      Patients made 15 hypothetical choices between two alternative PCI treatments
      described by four attributes: amount of life gained, chance of BM, ability to
      care for oneself, and loss of memory. Participants also chose between PCI and no
      PCI. RESULTS: 54 and 46 surveys were completed pre- and post-treatment. The most
      important attributes pre-treatment were: a survival benefit >6months, of 3
      6months, avoiding severe problems with memory and self-care, avoiding quite a bit
      of difficulty with memory and maximally reducing BM recurrence. Post-treatment,
      BM reduction became more important. 90% of patients would accept PCI for a
      survival benefit >6months, with a maximal reduction in BM even if severe
      memory/self-care problems occurred. With a 10% reduction in BM and mild problems
      with memory and self-care 70% of patients pre- (90% post-treatment) would accept
      PCI for a survival benefit of 1-3months, and 52% pre- (78% post-treatment) for no
      survival benefit. CONCLUSION: Improvement in survival is the most important
      attribute of PCI with patients willing to accept significant toxicity for maximum
      survival and less toxicity for less survival benefit. BM reduction became more
      important after treatment. The majority of patients would accept PCI for no
      survival benefit and a reduction in BM.

PMID- 27717513
TI  - [Ebola virus disease: Clinical presentation, prognosis and treatment].
AB  - The clinical spectrum of Ebola virus disease (EVD) ranges from very serious forms
      with organ failure and death within days to paucisymptomatic forms and perhaps
      even asymptomatic. The authors propose a focus on the clinical manifestations of
      EVD, on prognosis and on therapeutic aspects (excluding resuscitation). This work
      extracts from the literature the main data gathered during the 2014-2015 epidemic
      that raged in Guinea Conakry and Sierra Leone. These two countries, even if they
      are separated by a border, are one and the same population base. The
      characteristics of the epidemic in Liberia have not been analyzed. The authors
      have treated EVD patients in the health workers treatment center of Conakry and
      enrich this work about their personal experience.

PMID- 27717514
TI  - Adhesion of living cells to abutment materials, dentin, and adhesive luting
      cement with different surface qualities.
AB  - OBJECTIVE: We tested the adhesion properties of living gingival fibroblasts on
      three different implant abutment materials, adhesive resin used to bond bi
      partite abutments, and human dentin. METHODS: Discs of lithium disilicate (LS),
      zirconium dioxide (Zr), adhesive resin cement (AR), titanium (Ti), and human
      dentin (HD) were fabricated with three different levels of surface roughness
      (rough, machined, and polished). Ra and Rz, water contact angle, and cell
      detachment forces were measured. Cell detachment force was measured for single
      cells using single-cell force spectroscopy. Data were statistically analyzed
      using parametric tests (ANOVA, MANOVA, Bonferroni post-hoc tests). RESULTS:
      Surface roughness significantly influenced the water contact angle for all
      materials (P<=0.05). Overall, HD showed the lowest contact angle, followed by LS,
      Ti, Zr, and AR (P<=0.05). Comparison of cell detachment forces between materials
      with rough and machined surfaces revealed no significant differences (P>0.05),
      with the exception of Zr compared to HD with rough surfaces (P=0.006). For
      polished surfaces, HD showed the highest detachment force (P<=0.0001), followed
      by Ti, AR, and Zr, which did not significantly differ from each other (P>0.05)
      and LS; Ti/AR was significantly different from LS (P<=0.05). Except for HD, where
      polished surfaces exhibited the highest cell detachment force (P<=0.002), most
      machined surfaces showed higher cell detachment forces than polished or rough
      surfaces. SIGNIFICANCE: Implant abutments should ideally be provided with a
      machined like surface roughness for best cell adhesion.

PMID- 27717515
TI  - Shear-Wave Elastography: Could it be Helpful for the Diagnosis of Non-Mass-Like
      Breast Lesions?
AB  - The goal of this study was to analyze the diagnostic performance of shear wave
      elastography (SWE) in differentiation of benign and malignant non-mass-like (NML)
      breast lesions. Three hundred sixteen consecutive breast lesions in 305 patients
      who have been scheduled for ultrasound (US)-guided core needle biopsy or vacuum
      assisted biopsy or surgical excision between January 2013 and August 2013 were
      initially included in this study. Finally, 63 patients with 67 lesions classified
      as NML lesions comprised our study population. The features of SWE and its
      diagnostic performance in NML lesions were analyzed. Among the 67 NML lesions, 33
      were malignant and 34 were benign. The maximum elastic modulus, mean elastic
      modulus, minimum elastic modulus, elastic modulus ratio and stiff rim sign of the
      malignant lesions were all significantly higher than those of benign lesions (p <
      0.05). The combination of conventional US with maximum elastic modulus and stiff
      rim sign got significantly higher diagnostic specificity and positive predictive
      value (PPV) than conventional US (p < 0.05 for both). In the benign lesions, 23
      (67.6%) unnecessary biopsies could have been eliminated after the combination of
      conventional US and SWE. SWE could increase diagnostic specificity and positive
      predictive values of NML breast lesions. The combination of conventional US and
      SWE could reduce unnecessary benign biopsies of NML lesions.

PMID- 27717516
TI  - Ambient Pressure Evaluation Through Sub-Harmonic Response of Chirp-Sonicated
      Microbubbles.
AB  - The sub-harmonic response generated by oscillating ultrasound contrast
      microbubbles has been proven to be a potentially efficient and effective measure
      for non-invasive blood pressure evaluation. In this work, an improved approach to
      ambient pressure measurement is proposed, and the general principle underlying
      this approach is the combination of sub-harmonic responses of microbubbles with a
      chirp excitation technique. Agreement between theoretical and experimental
      studies indicates that compared with sinusoidal excitation, the chirp technique
      is beneficial in that it produces bubble sub-harmonics with higher amplitudes and
      lower generation thresholds and thus offers better sensitivity for ambient
      pressure evaluations. Studies that took the chirp parameters (e.g., central
      frequency, bandwidth and pulse length) into account were also carried out to
      determine an optimized routine for the proposed method.

PMID- 27717518
TI  - Hypersensitivity to aspirin and urgent percutaneous coronary intervention: A
      therapeutic challenge.
AB  - Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs are common and
      five types of reactions have been defined. The prevalence of such reactions in
      patients with myocardial infarction is unclear, and so antiplatelet therapy in
      this population is a challenge. Various desensitization protocols have been
      developed but there are no specific guidelines for their use. The authors present
      the case of a patient with acute coronary syndrome and aspirin hypersensitivity
      referred for urgent coronary angiography. Aspirin desensitization therapy is safe
      and successful in many patients, but more randomized trials are needed to confirm
      its benefits in coronary artery disease patients.

PMID- 27717517
TI  - Youth Acquisition and Situational Use of Cigars, Cigarillos, and Little Cigars::
      A Cross-sectional Study.
AB  - INTRODUCTION: Although adolescent use of cigars, cigarillos, and little cigars
      (CCLCs) has been increasing, little research has been conducted to understand how
      adolescents acquire CCLCs and the situations in which they smoke CCLCs. Thus,
      this study aims to understand how adolescent smokers acquire CCLCs and the
      situations in which they smoke them. METHODS: Data were drawn from the 2011
      Cuyahoga County Youth Risk Behavior Survey. Current CCLC smoking was assessed;
      analysis was limited to current smokers (n=1,337). Current users were asked to
      identify situations in which they use cigars and ways in which they get cigars.
      Bivariate analyses assessed differences by sex, race, and concurrent substance
      use. Data were analyzed in 2014. RESULTS: Youth acquired CCLCs most commonly by
      buying (64.2%). CCLC smokers also reported high rates of social use (81.1%).
      There were no significant differences is situational use across sexes, but female
      adolescents were significantly more likely than male adolescents to share CCLCs
      and significantly less likely to buy or take CCLCs. Conversely, significant
      differences were seen for situational use by race/ethnicity, with whites
      significantly more likely to use in social situations and less likely to use in
      solitary situations versus blacks and Hispanics. Finally, significant differences
      were observed in both acquisition and use for youth who concurrently used CCLCs
      and cigarettes compared with CCLCs only; fewer differences were noted among those
      who concurrently used CCLCs and marijuana compared with CCLCs only. CONCLUSIONS:
      These findings highlight how adolescents acquire and use CCLCs and can inform
      tobacco control strategies to prevent and reduce CCLC use.

PMID- 27717519
TI  - Central pressures and central hemodynamic values in white coat hypertensives are
      closer to those of normotensives than to those of controlled hypertensives for
      similar age, gender, and 24-h and nocturnal blood pressures.
AB  - INTRODUCTION: There is disagreement whether white coat hypertensives (WCH) have
      different hemodynamic and structural characteristics compared to normotensives
      (NT) and hypertensives (HT). METHODS: We compared cardiovascular prognostic
      markers (pulse wave velocity [PWV] and aortic stiffness index [ASI]) and data on
      central hemodynamics and central pressures (augmentation index [AIx],
      augmentation pressure [AugP] and pulse pressure amplification [PPA]) from aortic
      pulse wave analysis between NT (n=175), WCH (n=315) and treated HT (n=691), all
      with 24-h blood pressure (BP) <130/80 and nocturnal BP <120/70 mmHg after
      matching for age, gender, body mass index (BMI) and and nocturnal BP. The groups
      were also compared separately in terms of 24-h systolic BP <120 mmHg and 120-129
      mmHg. RESULTS: The percentage of non-dippers was 40.1% in NT, 34.5% in WCH and
      38.3 in HT. For similar 24-h and nocturnal systolic BP (NT 109/64+/-7/5, WCH
      110/66+/-7/6, HT 109/64+/-7/5 mmHg), aortic stiffness was greater in HT (n=691,
      PWV 10.8+/-2.6 m/s and ASI 0.33+/-0.16, p<0.01) than in WCH (n=316, PWV 9.7+/-2.4
      m/s and ASI 0.28+/-0.17) and NT (n=175, PWV 9.5+/-2.0 m/s and ASI 0.29+/-0.15);
      AugP and AIx were higher (p<0.01) in HT (13.9+/-8.2 and 29.6+/-12.6 mmHg) than in
      WCH (11.5+/-8.5 mmHg and 24.9+/-15.2) and NT (11.0+/-6.4 mmHg and 26.6+/-11.5).
      PPA was lower (p<0.01) in HT (11.3+/-5.5 mmHg) than in WCH (13.2+/-7.1 mmHg) and
      in NT (12.4+/-4.9 mmHg). The findings were similar when the 24-h systolic BP <120
      mmHg and 120-129 mmHg subgroups were analyzed separately. CONCLUSION: Our data
      suggest that for similar age, gender distribution, BMI, and 24-h and nocturnal
      BP, aortic stiffness, central aortic pressures and wave reflection in WCH are
      closer to those of NT than to those with treated HT. This supports the idea that
      white coat hypertension may be a more benign condition than treated hypertension
      for similar 24-h and particularly nocturnal BP levels.

PMID- 27717520
TI  - The appropriate age to study the incidence of Helicobacter pylori infection.

PMID- 27717521
TI  - Re: Par Stattin, Fredrik Sandin, Frederik Birkebaek Thomsen, et al. Association
      of Radical Local Treatment with Mortality in Men with Very High-risk Prostate
      Cancer: A Semiecologic, Nationwide, Population-based Study. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2016.07.023: Radical Treatment in Very High
      risk Prostate Cancer: Venturing Down a Path Less Travelled.

PMID- 27717523
TI  - Role for coronin 1 in mouse NK cell function.
AB  - Coronin 1, a member of the evolutionary conserved WD repeat protein family of
      coronin proteins is expressed in all leukocytes, but a role for coronin 1 in
      natural killer (NK) cell homeostasis and function remains unclear. Here, we have
      analyzed the number and functionality of NK cells in the presence and absence of
      coronin 1. In coronin 1-deficient mice, absolute NK cell numbers and phenotype
      were comparable to wild type mice in blood, spleen and liver. Following in vitro
      stimulation of the activating NK cell receptors NK1.1, NKp46, Ly49D and NKG2D,
      coronin 1-deficient NK cells were functional with respect to interferon-gamma
      production, degranulation and intracellular Ca2+ mobilization. Also, both wild
      type as well as coronin 1-deficient NK cells showed comparable cytotoxic
      activity. Furthermore, activation and functionality of NK cells following
      Vesicular Stomatitis Virus (VSV) infection was similar between wild type and
      coronin 1-deficient mice. Taken together these data suggest that coronin 1 is
      dispensable for mouse NK cell homeostasis and function.

PMID- 27717522
TI  - Comparative Effectiveness of Newer Medications for Lower Urinary Tract Symptoms
      Attributed to Benign Prostatic Hyperplasia: A Systematic Review and Meta
      analysis.
AB  - CONTEXT: Alpha-blockers (ABs) and 5-alpha reductase inhibitors have an
      established role in treating male lower urinary tract symptoms (LUTS) attributed
      to benign prostatic hyperplasia (BPH). Recently, newer drugs have shown promise
      for this indication. OBJECTIVE: To assess the comparative effectiveness and
      adverse effects (AEs) of newer drugs to treat LUTS attributed to BPH through a
      systematic review and meta-analysis. EVIDENCE ACQUISITION: Ovid MEDLINE, the
      Cochrane Central Register of Controlled Trials, and Ovid Embase bibliographic
      databases (through June 2016) were hand searches for references of relevant
      studies. Eligible studies included randomized controlled trials published in
      English of newer ABs, antimuscarinics, a beta-3 adrenoceptor agonist,
      phosphodiesterase type-5 inhibitors, or combination therapy with one of these
      medications as an active comparator. Observational studies of the same agents
      with a duration >=1 yr that reported AEs were also included. EVIDENCE SYNTHESIS:
      We synthesized evidence from 43 randomized controlled trials as well as five
      observational studies. Based on improvement of mean International Prostate
      Symptom Score and quality of life scores, the effectiveness of the newer ABs was
      not different from the older ABs (moderate strength of evidence [SOE]), but had
      more AEs (low SOE). Antimuscarinics/AB combination therapy had similar outcomes
      as AB monotherapy (all moderate SOE), but often had more AEs. Phosphodiesterase
      type-5 inhibitors alone or in combination with ABs had similar or inferior
      outcomes than ABs alone. Evidence was insufficient for the beta-3 adrenoceptor
      agonist. For all newer agents, the evidence was generally insufficient to assess
      long-term efficacy, prevention of symptom progression, or AEs. CONCLUSIONS: None
      of the drugs or drug combinations newly used to treat LUTS attributed to BPH
      showed outcomes superior to traditional AB treatment. Given the lack of superior
      outcomes, the studies' short time-horizon, and less assurance of their safety,
      their current value in treating LUTS attributable to BPH appears low. PATIENT
      SUMMARY: In this paper, we reviewed the evidence of newer drugs to treat men with
      urinary problems attributable to an enlarged prostate. We found none of the new
      drugs to be better but there was more concern about side effects.

PMID- 27717524
TI  - STA-21, a STAT-3 inhibitor, attenuates the development and progression of
      inflammation in collagen antibody-induced arthritis.
AB  - We set out to investigate the influence of STA-21, a dynamic STAT-3 inhibitor, on
      the expansion and progression of rheumatoid arthritis (RA), and to determine its
      potential mechanisms of action in a mouse model of collagen antibody-induced
      arthritis (CAIA). To this end, arthritis was induced via intravenous (IV)
      injection of Balb/c mice with a cocktail of antibodies directed against type II
      collagen (1.5MUg/mouse, IV), followed by lipopolysaccharide (LPS) at a dose of
      (25MUg/mouse, i.p.) on day 3. Mice were then left untreated or were
      simultaneously treated with STA-21 (0.5mg/kg, i.p., once daily for 2 weeks)
      followed by evaluation for clinical and histological features of arthritic
      inflammation and flow cytometric analysis of cytokines and transcription factors
      in peripheral blood. STA-21 enhanced the clinical course of arthritis in CAIA
      mice and decreased CD8+RORgammat+ and CD8+IL-21+ cells while inducing the
      production of CD8+Foxp3+ cells. Furthermore, STA-21 prevented the production of
      TNF-alpha and IL-6 in peripheral blood and increased IL-27 production by CD14+
      cells. Moreover, STA-21 not only regulates Th1/Th2 serum cytokine levels but also
      the mRNA and protein expression of key factors including NF-kappaB p65,
      RORgammat, T-bet, IL-4, GATA-3, JAK1, Stat3, and IL-21. Thus, administration of
      the Stat3 inhibitor STA-21 inhibits cellular signaling pathways and downstream
      activation of key transcription factors previously shown to play key roles in the
      pathogenesis of RA. Therefore, these data suggest that STA-21 could be considered
      as a potential treatment for patients with RA.

PMID- 27717525
TI  - Cardiac Magnetic Resonance Imaging, Transcatheter Aortic Valve Replacement, and
      Early Left Ventricular Mass Regression-A Virtual Microscope Into Ventricular
      Remodelling?

PMID- 27717526
TI  - Human brucellosis in France in the 21st century: Results from national
      surveillance 2004-2013.
AB  - : Brucellosis is a bacterial zoonotic disease mainly transmitted to humans by
      ruminants. In France, brucellosis has disappeared from ruminants herds. Human
      brucellosis surveillance is performed through mandatory notification and the
      national reference center. METHODS: We report the results of human brucellosis
      surveillance from 2004 to 2013 with regards to epidemiological, clinical and
      microbiological data. RESULTS: A total of 250 cases were notified, making an
      annual incidence of 0.3 cases per million inhabitants. Brucella melitensis biovar
      3 was the most frequently identified bacterium (79% of isolated strains). In
      total, 213 (85%) cases had been contaminated abroad in endemic countries. In
      2012, an episode of re-emergence of brucellosis in cattle occurred in Haute
      Savoie, in the French Alps, and was responsible for 2 human cases. CONCLUSION:
      Brucellosis has become a disease of travelers in France. However, maintaining a
      stringent epidemiological surveillance is necessary to be able to early detect
      any local re-emergence in humans or animals. The multidisciplinary surveillance
      was implemented in France years ago and is a successful example of the One Health
      Concept.

PMID- 27717527
TI  - Association of Traumatic and Atraumatic Posterior Shoulder Instability With
      Glenoid Retroversion and Outcomes After Arthroscopic Capsulolabral Repair.
AB  - PURPOSE: To compare glenoid retroversion and functional outcomes between patients
      with traumatic onset of posterior shoulder instability (PSI) and patients with
      atraumatic onset of PSI. METHODS: Patients with PSI who underwent arthroscopic
      posterior capsulolabral anchor repair, were active in sports, and had undergone
      surgery a minimum of 2 years earlier were included. Traumatic onset was defined
      as PSI that occurred after a trauma with the shoulder in adduction, flexion, and
      internal rotation in patients with no history of instability. Subjective
      evaluations were obtained with the American Shoulder and Elbow Surgeons (ASES);
      Quick Disabilities of the Arm, Shoulder and Hand; Single Assessment Numeric
      Evaluation (SANE); and Short Form 12 Physical Component Summary scores
      preoperatively and after a minimum 2-year follow-up postoperatively. Additional
      questions assessed return to sport and shoulder stability. Glenoid version was
      measured with a 2-dimensional glenoid vault method on magnetic resonance imaging.
      RESULTS: A total of 41 shoulders in 38 patients were eligible for inclusion (3
      female and 35 male patients; mean age, 27.6 years; age range, 13 to 66 years).
      Three patients refused participation, and 2 patients required subsequent surgery
      for failure. Postoperative outcomes were available for 32 of the remaining 36
      shoulders (89%) with a mean follow-up of 4.1 years (range, 2.0 to 7.8 years; 20
      atraumatic and 12 traumatic). The ASES score improved significantly in both
      groups (P < .03), whereas the SANE; Quick Disabilities of the Arm, Shoulder and
      Hand; and Short Form 12 Physical Component Summary scores only significantly
      improved for patients with traumatic PSI (P < .02). Baseline score-adjusted
      comparison between groups showed that the postoperative median ASES scores
      (atraumatic, 95.8; traumatic, 99.9) and SANE scores (atraumatic, 86.5; traumatic,
      98.0) were significantly more improved in patients with traumatic PSI (P = .01
      and P = .012, respectively). Atraumatic PSI was associated with significantly
      higher glenoid retroversion (-21.8 degrees  +/- 4.2 degrees  vs -17.7 degrees  +/
      5.5 degrees , P = .032). There was no significant difference regarding return to
      sport (P = .375) or postoperative re-dislocations (P = .99) between the groups.
      CONCLUSIONS: Atraumatic onset of PSI was associated with higher degrees of
      glenoid retroversion and less favorable functional outcomes of arthroscopic
      posterior capsulolabral anchor repair than traumatic PSI. LEVEL OF EVIDENCE:
      Level III, retrospective case-control study.

PMID- 27717528
TI  - Inferior mesenteric artery lymph node metastasis in rectal cancer treated with
      neoadjuvant chemoradiotherapy: Incidence, prediction and prognostic impact.
AB  - AIM: To assess the effect of neoadjuvant chemoradiotherapy (nCRT) on inferior
      mesenteric artery (IMA) nodal metastasis and identify predictors for IMA nodal
      metastasis in locally advanced rectal cancer (LARC) after nCRT. METHOD:
      Propensity score matching of 1167 patients with LARC was performed.
      Clinicopathological predictors and survival rates were analyzed using univariate
      and multivariate analyses. RESULTS: Compared to surgery alone, nCRT reduced the
      incidence of IMA nodal metastasis (before matching, 4.8% vs 9.1%, p = 0.004;
      after matching, 4.3% vs 10.1%, p = 0.002). Logistic regression analysis revealed
      that poorly differentiated (OR = 5.955, p < 0.001), tumors located above the
      peritoneal reflection (OR = 3.513, p = 0.005), and preoperative CEA levels ?10
      ng/ml (OR = 4.774, p = 0.005) were associated with IMA nodal metastasis. Time
      intervals to surgery ?6 weeks were associated with fewer IMA nodal metastasis (OR
      = 0.274, p = 0.009).Over a median 40-month follow-up, the 3-year overall survival
      and disease-free survival rates were 63.0% and 43.1% in IMA-positive patients,
      respectively, which were significantly lower than the corresponding 89.0% and
      82.4% rates in IMA-negative patients. Cox regression analysis revealed that IMA
      nodal metastasis was independently associated with unfavorable 3-year DFS.
      CONCLUSION: nCRT reduced the incidence of IMA node metastasis. Tumors located
      above the peritoneal reflection, poorly differentiated, and higher preoperative
      CEA levels were associated with IMA nodal metastasis after nCRT. IMA lymph node
      dissection is beneficial to certain patients with IMA nodal metastases, and the
      oncologic benefit may be improved if IMA nodal metastasis can be predicted.

PMID- 27717529
TI  - Individualizing surgical treatment based on tumour response following neoadjuvant
      therapy in T4 primary rectal cancer.
AB  - BACKGROUND: Rectal cancer involving at least one adjacent organ (mrT4b) requires
      multi-visceral resection to achieve clear resection margin (R0). Performing
      pelvic compartment preservation according to the tumour response has not been
      considered. This study assesses the impact of changing the surgical strategy
      according to tumour response in rectal cancer mrT4b. METHODS: Patients with non
      metastatic T4b rectal cancer at two tertiary referral centres between 2008 and
      2013 were grouped as "Responders" ypT0-3abNx versus "Non-responders" ypT3cd-4Nx
      and divided into three surgical procedures: total mesorectal excision (TME),
      extended-TME (eTME) and beyond-TME (b-TME). End-points were circumferential
      resection margin, postoperative morbidity, definitive stoma formation, 3-years
      local recurrence (3y-LR) and 3-years disease-free survival (3y-DFS) according to
      both tumours' response and surgical procedures. RESULTS: Among 883 patients with
      rectal cancer, 101 were included. Responders had a higher rate of induction
      chemotherapy (59.7% vs. 38.2%; p = 0.04). Morbidity and definitive stoma
      formation were significantly higher in Non-responders. R0 was not impacted by
      either the tumour response or the surgical procedures. The 3y-LR was lower in
      Responders (14%) compared to Non Responders (32%) (HR 1.6; 95% CI: 1.02-2.59; p =
      0.041), and was two-fold higher in e-TME compared to b-TME in Non-responders,
      whereas no difference was found in Responders. The 3y-DFS was higher in
      Responders irrespective to the surgery (71% vs. 47%; p = 0.07). CONCLUSION: In
      Responders, TME or e-TME are technically and oncollogically feasible and should
      be considered in preferrence to b-TME. In Non-responders, allowing for high rates
      of morbidity and local recurrence in patients with e-TME, b-TME procedures should
      be preferred.

PMID- 27717530
TI  - Effect of silver nano-particles on soil microbial growth, activity and community
      diversity in a sandy loam soil.
AB  - Silver nano-particles (AgNPs) are widely used in a range of consumer products as
      a result of their antimicrobial properties. Given the broad spectrum of uses,
      AgNPs have the potential for being released to the environment. As a result,
      environmental risks associated with AgNPs need to be assessed to aid in the
      development of regulatory guidelines. Research was performed to assess the
      effects of AgNPs on soil microbial activity and diversity in a sandy loam soil
      with an emphasis on using a battery of microbial tests involving multiple
      endpoints. The test soil was spiked with PVP coated (0.3%) AgNPs at the following
      concentrations of 49, 124, 287, 723 and 1815 mg Ag kg-1 dry soil. Test controls
      included an un-amended soil; soil amended with PVP equivalent to the highest PVP
      concentration of the coated AgNP; and soil amended with humic acid, as 1.8% humic
      acid was used as a suspension agent for the AgNPs. The impact on soil microbial
      community was assessed using an array of tests including heterotrophic plate
      counting, microbial respiration, organic matter decomposition, soil enzyme
      activity, biological nitrification, community level physiological profiling
      (CLPP), Ion TorrentTM DNA sequencing and denaturing gradient gel electrophoresis
      (DGGE). An impact on microbial growth, activity and community diversity was
      evident from 49 to 1815 mg kg-1 with the median inhibitory concentrations (IC50)
      as low as 20-31 mg kg-1 depending on the test. AgNP showed a notable impact on
      microbial functional and genomic diversity. Emergence of a silver tolerant
      bacterium was observed at AgNP concentrations of 49-287 mg kg-1 after 14-28 days
      of incubation, but not detectable at 723 and 1815 mg kg-1. The bacterium was
      identified as Rhodanobacter sp. The study highlighted the effectiveness of using
      multiple microbial endpoints for inclusion to the environmental risk assessment
      of nanomaterials.

PMID- 27717531
TI  - Size distribution of stranded small plastic debris on the coast of Guangdong,
      South China.
AB  - Beach environments are known to be conducive to fragmentation of plastic debris,
      and highly fragmented plastic particles can interact with smaller organisms. Even
      through stranded plastic debris may not interact directly with marine organisms,
      backwash processes may transport this debris back to coastal waters, where it may
      affect a wide range of marine life at different trophic levels. This study
      analysed the size distribution of stranded plastic debris (<10 mm) collected from
      eight coastal beaches in Guangdong Province, China. Polystyrene (PS) foams and
      fragments smaller than 7 mm were increasingly abundant in the smaller size
      classes, whereas resin pellets remained in their production sizes (~3 mm).
      Microplastics (<5 mm) accounted for over 98% of the total plastic debris by
      abundance and 71% by weight, indicating that the plastic debris on these coastal
      beaches was highly fragmented and the majority of the plastic masses belonged to
      the microplastic size range. The observed size distributions of PS foams and
      fragments are believed to result from continued fragmentation. Previous studies
      found that the residence time of beached debris was less than one year on
      average, and no sign of plastic accumulation with depth in beach sediment was
      observed. Therefore, coastal beaches may represent a reservoir of highly
      fragmented and degraded microplastics that may be mobilised and returned to the
      sea during storm events. Further research on the dynamics and longevity of
      microplastics on beaches will help reveal the mass balance of microplastics on
      the shoreline and determine whether shorelines are sinks or sources of
      microplastics.

PMID- 27717533
TI  - Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian
      Cells.
AB  - Accumulating evidence suggests that mammalian cells asymmetrically segregate
      cellular components ranging from genomic DNA to organelles and damaged proteins
      during cell division. Asymmetric inheritance upon mammalian cell division may be
      specifically important to ensure cellular fitness and propagate cellular potency
      to individual progeny, for example in the context of somatic stem cell division.
      We review here recent advances in the field and discuss potential effects and
      underlying mechanisms that mediate asymmetric segregation of cellular components
      during mammalian cell division.

PMID- 27717532
TI  - Decision-making and goal-setting in chronic disease management: Baseline findings
      of a randomized controlled trial.
AB  - OBJECTIVE: Growing interest in collaborative goal-setting has raised questions.
      First, are patients making the 'right choices' from a biomedical perspective?
      Second, are patients and providers setting goals of appropriate difficulty?
      Finally, what types of support will patients need to accomplish their goals? We
      analyzed goals and action plans from a trial of collaborative goal-setting among
      302 residents of a high-poverty urban region who had multiple chronic conditions.
      METHODS: Patients used a low-literacy aid to prioritize one of their chronic
      conditions and then set a goal for that condition with their primary care
      provider. Patients created patient-driven action plans for reaching these goals.
      RESULTS: Patients chose to focus on conditions that were in poor control and set
      ambitious chronic disease management goals. The mean goal weight loss -16.8lbs
      (SD 19.5), goal HbA1C reduction was -1.3% (SD 1.7%) and goal blood pressure
      reduction was -9.8mmHg (SD 19.2mmHg). Patient-driven action plans spanned domains
      including health behavior (58.9%) and psychosocial (23.5%). CONCLUSIONS: High
      risk, low-SES patients identified high priority conditions, set ambitious goals
      and generate individualized action plans for chronic disease management. PRACTICE
      IMPLICATIONS: Practices may require flexible personnel who can support patients
      using a blend of coaching, social support and navigation.

PMID- 27717534
TI  - Piecing Together the Patchwork of Contact Sites.
AB  - Contact sites are places where two organelles join together to carry out a shared
      activity requiring nonvesicular communication. A large number of contact sites
      have been discovered, and almost any two organelles can contact each other.
      General rules about contacts include constraints on bridging proteins, with only
      a minority of bridges physically creating contacts by acting as 'tethers'. The
      downstream effects of contacts include changing the physical behaviour of
      organelles, and also forming biochemically heterogeneous subdomains. However,
      some functions typically localized to contact sites, such as lipid transfer, have
      no absolute requirement to be situated there. Therefore, the key aspect of
      contacts is the directness of communication, which allows metabolic channelling
      and collective regulation.

PMID- 27717535
TI  - Trends in major opioid analgesic consumption in Taiwan, 2002-2014.
AB  - BACKGROUND/PURPOSE: According to WHO guideline, the consumption of opioids is an
      important sign of national progress in cancer pain relief. However, precise data
      on the consumption of opioid analgesics consumption in Taiwan has not been
      published. We investigate opioid analgesic consumption in Taiwan between 2002 and
      2014 compare the results with those in other countries to see what we could learn
      about other methods of pain management. To find out the different patterns
      between Taiwan and other country, improves the quality of pain management.
      METHODS: We extracted from the Controlled Drugs Management Information System
      (CDMIS) database, the consumption data of morphine, fentanyl, and pethidine,
      three strong opioids, and of codeine and buprenorphine, two weak ones. Data were
      presented as defined daily doses for statistical purposes per million inhabitants
      per day (S-DDD/m/d). The number of inhabitants was extracted from the Taiwan
      Ministry of Interior Statistics population database. RESULTS: During the thirteen
      studied years, the total consumption of opioids markedly increased in Taiwan. By
      category, the consumption of morphine, fentanyl and buprenorphine increased, but
      the use of pethidine and codeine decreased. Compared with the selected regions
      and countries, the use of opioid in Taiwan progressed in Asia, but it was still
      lower than in Western countries. CONCLUSION: Opioid analgesics are probable
      addictive; however, they can improve a patients' quality of life if properly
      used. The Taiwan FDA continuously introduces new opioid analgesics and educates
      physicians on how to use them correctly. These measures will improve the quality
      of pain management in Taiwan.

PMID- 27717536
TI  - The hypoxia-inducible factor (HIF) couples immunity with metabolism.
AB  - Crosstalk between metabolic and immune pathways has recently become appreciated
      to be key to the regulation of host defence. The hypoxia-inducible factor (HIF)
      is a transcription factor which was initially described as a ubiquitous master
      regulator of the transcriptional response to hypoxia. In this role, HIF regulates
      genes promoting adaptation to hypoxia including a number which influence the
      cellular metabolic strategy of a cell. It has more recently been appreciated that
      the regulation of HIF is not restricted to oxygen-dependent pathways, and is now
      known to be mediated by a number of additional metabolic and immune cues
      including metabolites and cytokines respectively. Furthermore, our understanding
      of the functional role of HIF has expanded to it now being appreciated as a major
      regulator of host immunity. This places HIF in an ideal position to act as a
      regulatory hub which links metabolic activity with immunity. In this review we
      synthesise recent data which identifies HIF as both a target and effector for
      metabolic and immune processes. Developing our understanding of the role of HIF
      in this context will uncover new therapeutic targets for inflammatory and
      infectious disease.

PMID- 27717537
TI  - Editorial commentary: The challenge to optimize cardiovascular disease risk
      management in patients with rheumatoid arthritis.

PMID- 27717539
TI  - Is Heart Disease or Cancer the Leading Cause of Death in United States Women?
AB  - PURPOSE: This paper compares the mortality burden of heart disease versus cancer
      among women by age, race, and ethnicity. METHODS: U.S. death and population data
      for the years 2000 through 2013 were used to calculate heart disease and cancer
      death rates. Detailed analyses focused on age (15-19 years old to >=100 years
      old) and race and ethnicity (Whites, Blacks, Hispanics, Asians and Pacific
      Islanders (A/PIs), and American Indians and Alaska Natives (AI/ANs)). RESULTS:
      Among women aged 15 years and older, there were 289,467 heart disease deaths and
      276,716 cancer deaths in 2013. The majority of heart disease deaths (51.6%)
      occurred among women 85 years or older, compared with 18.9% of female cancer
      deaths. The age-adjusted death rates (per 100,000 population) were 171 (95%
      confidence interval [CI], 170-171) for heart disease versus 177 (95% CI, 176-178)
      for cancer. For all racial and ethnic groups, cancer mortality was significantly
      higher than heart disease mortality among women younger than 80 years of age. For
      all ages combined, cancer deaths exceeded heart disease deaths among Hispanics,
      A/PIs, and AI/ANs. Black non-Hispanic women were the only racial/ethnic group who
      had a higher age-adjusted death rate for heart disease than for cancer: 224 (95%
      CI, 222-226) versus 207 (95% CI, 205-209). CONCLUSIONS: Heart disease remains the
      leading cause of death among all women combined in the United States by a narrow
      margin. However, cancer predominantly kills middle-aged and young women, whereas
      heart disease predominantly kills the very old. New research on the overreporting
      of heart disease on death certificates for elderly women is needed. National
      summary statistics obscure the fact that cancer is already the overall leading
      cause of death for Hispanic women, Asian and Pacific Islander women, and American
      Indian and Alaska Native women.

PMID- 27717538
TI  - Non-invasive assessment of low- and intermediate-risk patients with chest pain.
AB  - Coronary artery disease (CAD) remains a significant global public health burden
      despite advancements in prevention and therapeutic strategies. Common non
      invasive imaging modalities, anatomic and functional, are available for the
      assessment of patients with stable chest pain. Exercise electrocardiography is a
      long-standing method for evaluation for CAD and remains the initial test for the
      majority of patients who can exercise adequately with a baseline interpretable
      electrocardiogram. The addition of cardiac imaging to exercise testing provides
      incremental benefit for accurate diagnosis for CAD and is particularly useful in
      patients who are unable to exercise adequately and/or have uninterpretable
      electrocardiograms. Radionuclide myocardial perfusion imaging and
      echocardiography with exercise or pharmacological stress provide high sensitivity
      and specificity in the detection and further risk stratification of patients with
      CAD. Recently, coronary computed tomography angiography has demonstrated its
      growing role to rule out significant CAD given its high negative predictive
      value. Although less available, stress cardiac magnetic resonance provides a
      comprehensive assessment of cardiac structure and function and provides a high
      diagnostic accuracy in the detection of CAD. The utilization of non-invasive
      testing is complex due to various advantages and limitations, particularly in the
      assessment of low- and intermediate-risk patients with chest pain, where no
      single study is suitable for all patients. This review will describe currently
      available non-invasive modalities, along with current evidence-based guidelines
      and appropriate use criteria in the assessment of low- and intermediate-risk
      patients with suspected, stable CAD.

PMID- 27717540
TI  - Notch sensitivity jeopardizes titanium locking plate fatigue strength.
AB  - INTRODUCTION: Notch sensitivity may compromise titanium-alloy plate fatigue
      strength. However, no studies providing head-to-head comparisons of stainless
      steel or titanium-alloy locking plates exist. MATERIALS AND METHODS: Custom
      designed identically structured locking plates were made from stainless steel
      (F138 and F1314) or titanium alloy. Three screw-hole designs were compared:
      threaded screw-holes with angle edges (type I); threaded screw-holes with
      chamfered edges (type II); and non-threaded screw-holes with chamfered edges
      (type III). The plates' bending stiffness, bending strength, and fatigue life,
      were investigated. The stress concentration at the screw threads was assessed
      using finite element analyses (FEA). RESULTS: The titanium plates had higher
      bending strength than the F1314 and F138 plates (2.95:1.56:1) in static loading
      tests. For all metals, the type-III plate fatigue life was highest, followed by
      type-II and type-I. The type-III titanium plates had longer fatigue lives than
      their F138 counterparts, but the type-I and type-II titanium plates had
      significantly shorter fatigue lives. All F1314 plate types had longer fatigue
      lives than the type-III titanium plates. The FEA showed minimal stress difference
      (0.4%) between types II and III, but the stress for types II and III was lower
      (11.9% and 12.4%) than that for type I. CONCLUSIONS: The screw threads did not
      cause stress concentration in the locking plates in FEA, but may have jeopardized
      the fatigue strength, especially in the notch-sensitive titanium plates.
      Improvement to the locking plate design is necessary.

PMID- 27717541
TI  - The efficacy of a novel saline/bipolar radiofrequency energy instrument for
      arresting ongoing solid and non-solid organ hemorrhage in a swine model.
AB  - INTRODUCTION: Ongoing hemorrhage is often life threatening and can be challenging
      to stop in critically injured patients. Traditional techniques for addressing
      this issue include high voltage cautery (Bovie), topical hemostatic application,
      and the delivery of ignited argon gas. The goal of this study was to evaluate the
      efficacy of a novel energy device for arresting ongoing bleeding from both solid
      and non-solid organs within a swine model. METHODS: A novel instrument utilizing
      bipolar radiofrequency (RF) energy which acts to ignite/boil dripping saline from
      a small hand piece was employed to arrest ongoing hemorrhage from an escalating
      series of injuries in large male swine. Liver, spleen, kidney, lung, heart,
      inferior vena cava and abdominal wall targets were evaluated and digitally
      recorded. Methodology was descriptive. RESULTS: Four large male swine received
      escalating injuries to their liver, spleen, kidney, lung, heart, inferior vena
      cava and abdominal wall. Injury patterns included a variety of surface
      decapsulation, superficial lacerations, deep lacerations, "through and through"
      missiles and complete transections. Application of the bipolar/RF instrument to
      sites of ongoing hemorrhage was successful in 97% of all scenarios. Depth of
      tissue penetration via microscopic evaluation ranged from 1.1mm to 3.0mm
      depending on the target organ composition. No air leaks were observed following
      application to the bleeding lung. Surgeon reported 'ease of use' score was high
      (4.8/5). CONCLUSION: This energy technology is successful in arresting ongoing
      hemorrhage from varying intensities of traumatic injuries to the liver, spleen,
      kidney, abdominal wall, lung and heart in the swine model. Additional testing is
      required before advocating its use on any thoracic organs.

PMID- 27717542
TI  - Is radiograph glenopolar angle accurate for extraarticular scapular neck
      fractures?
AB  - BACKGROUND: Plain radiographs still play a role in management of extraarticular
      scapular neck fractures. Glenopolar angle (GPA) is one of the radiograph
      measurements that is used to determine the necessity for surgery. Our aim was to
      establish reliability of GPA on plain radiograph in patients with extraarticular
      scapular neck fractures. METHODS: We performed a multicentre retrospective study
      including all patients with extraarticular scapular neck fractures with available
      imaging between 2006 and 2012. We excluded intra-articular glenoid fractures,
      scapular blade fractures, acromion fractures, and scapular spine fractures. We
      compared GPA on plain radiograph with three dimensional computed tomography (3D
      CT) measurement, as well as contribution of radiograph rotational error, glenoid
      inclination, and medial shortening of glenoid fragment towards GPA measurement.
      RESULTS: One hundred patients met the inclusion criteria. The mean difference
      between the GPA measurements on radiographs and 3D CT was 6.1+/-0.85 degrees 
      (95% confidence interval) as an absolute value. In terms of contribution to GPA
      values, GPA changed by one degree with ten degrees of radiograph rotational
      error, three degrees of glenoid inclination, and three millimetres of glenoid
      fragment medial shortening. CONCLUSION: Plain radiograph can provide a clinician
      with a reasonable estimation of the GPA. Glenoid inclination has a greater
      influence on GPA compared to medial shortening.

PMID- 27717543
TI  - [Obsessive-compulsive disorder as seen by those who are confronted with it: A
      survey of patients, relatives and clinicians].
AB  - INTRODUCTION: Obsessive compulsive disorder (OCD) is one of the most disabling
      mental health disorders due to its negative impact on the patient's quality of
      life as well on that of her living caregivers. This disorder generates an
      additional burden for relatives, which may in turn affect the family dynamics and
      impair the evolution of the disease. Along with medications, cognitive behavioral
      therapy (CBT) represents a well-validated first line of treatment for OCD.
      However, therapeutic responses across patients are uneven with often residual
      symptoms and limited quality of life improvements. In total, OCD is a severely
      debilitating disease with repercussions on both personal, social and professional
      lives of patients and their relatives even after clinically-delivered treatments.
      The mutual identification of points of convergence and divergence in social
      representations is a factor that contributes to satisfactory interpersonal
      relationships. In the care relationship in general and particularly in the field
      of mental health, taking account of these different representations and
      expectations is essential for improving the care process: upstream of the care in
      the choice the therapeutic strategy and in strengthening the therapeutic
      alliance. Although less studied, the relationship with relatives of patients also
      depends on representations of each which have a significant impact on clinical
      outcomes and experience of the disease. OBJECTIVE: To carry out the first study
      of cross-representations of OCD in three groups of people affected by it: those
      who suffer, their families and clinicians. HYPOTHESIS: Considering the
      experiences and knowledge of patients, relatives and clinicians, we assumed that
      their representations related to OCD would partially overlap. Specifically, we
      assumed that the positioning of each population compared to the other two would
      differ depending on the investigated dimensions: nosology, etiology, therapy and
      psychiatric disability. METHODS: From 2010 to 2011 we conducted an online survey
      among self-declared OCD-patients (n=86), OCD-patients' relatives (n=38) and
      clinicians (n=79). The questionnaire included both closed questions regarding the
      nosology, etiology, therapy and psychiatric disabilities and open questions
      probing the representations of the disorder and its evolution, its impact on
      personal, social and professional domains, and on the quality of life. In
      particular, we investigated how each population conceived the role and
      involvement of the relatives in the care process and how they dealt daily with
      the disorder. RESULTS: Confirming our hypothesis, our results showed that
      representations of OCD converge on the DSM-based definition of the disorder
      conveyed by patient associations and mass media. The three populations also
      recognize the burden and the handicap associated with OCD considerably restrict
      their daily functioning. However, patients and relatives differ from clinicians
      in their view of the etiology and their expectations of the therapeutic process.
      Unexpectedly, patients do not report frequent stigmatization although this may
      reflect their attempt to hide their disorder as a form of self-stigmatization.
      Patients focus on care modalities (alternative therapies) motivated by quality of
      life improvement rather than symptom reduction put forward by clinicians.
      Relatives ask for being involved in the care process. CONCLUSION: Our study
      emphasizes the importance for health professionals to take into account the
      expectations of patients and their relatives in order to maximize the therapeutic
      alliance and efficiency of treatment.

PMID- 27717544
TI  - Targeting prostate cancer with compounds possessing dual activity as androgen
      receptor antagonists and HDAC6 inhibitors.
AB  - While enzalutamide and abiraterone are approved for treatment of metastatic
      castration-resistant prostate cancer (mCRPC), approximately 20-40% of patients
      have no response to these agents. It has been stipulated that the lack of
      response and the development of secondary resistance to these drugs may be due to
      the presence of AR splice variants. HDAC6 has a role in regulating the androgen
      receptor (AR) by modulating heat shock protein 90 (Hsp90) acetylation, which
      controls the nuclear localization and activation of the AR in androgen-dependent
      and independent scenarios. With dual-acting AR-HDAC6 inhibitors it should be
      possible to target patients who don't respond to enzalutamide. Herein, we
      describe the design, synthesis and biological evaluation of dual-acting compounds
      which target AR and are also specific towards HDAC6. Our efforts led to compound
      10 which was found to have potent dual activity (HDAC6 IC50=0.0356MUM and AR
      binding IC50=<0.03MUM). Compound 10 was further evaluated for antagonist and
      other cell-based activities, in vitro stability and pharmacokinetics.

PMID- 27717545
TI  - Six new compounds from Atractylodes lancea and their hepatoprotective activities.
AB  - Two new phenolic glycosides with a rare beta-d-glucopyranosyl-(1->3)-alpha-l
      rhamnopyranosyl moiety (1, 2), one new dihydrobenzofuran derivative (3), one new
      pyrazine derivative (4), two new furofuran lignan glycosides (5, 6), and six
      known compounds (7-12) were isolated from the rhizomes of Atractylodes lancea.
      The structures of these compounds were elucidated by extensive spectroscopic
      analyses combined with the experimental and calculated electronic circular
      dichroism and the Rh2(OCOCF3)4-induced circular dichroism for configurational
      assignments. Notably, compounds 1-3 showed significant hepatoprotective
      activities against N-acetyl-p-aminophenol-induced HepG2 cell injury. This study
      is also the first Letter on the isolation of furofuran lignans and pyrazine
      derivatives (4-7) from the genus Atractylodes.

PMID- 27717547
TI  - Femur, tibia and fibula bone templates to estimate subject-specific knee ligament
      attachment site locations.
AB  - In-vivo estimates of the positions of knee ligament attachment sites are crucial
      for subject-specific knee modelling. The present study provides template digital
      models of femur, tibia and fibula that embed the positions of centroids of the
      origins and insertions of cruciate and collateral ligaments, along with
      information on their dispersion related to inter-individual variability. By using
      a shape transformation procedure of choice, these templates can be made to match
      anatomical information measured on a subject under analysis. Generic bone digital
      models of the femur, tibia and fibula were first chosen as bone templates.
      Ligament attachment areas were accurately identified through dissection on the
      bones of 11 knee specimens, and marked using radio opaque paint. Digital models
      of these bones embedding the positions of the centroids of the identified
      ligament attachment areas were thereafter obtained using medical imaging
      techniques. These centroids were mapped onto the relevant bone template, thus
      obtaining a cloud of 11 points for each attachment site, and descriptive
      statistics of the position of these points were thereafter determined. Dispersion
      of these positions, essentially due to inter-individual variability, was below
      6mm for all attachment areas. The accuracy with which subject-specific ligament
      attachment site positions may be estimated using the bone template models
      provided in this paper was also assessed using the above-mentioned 11 specimens
      data set, and a leave-one-out cross validation approach. Average accuracy was
      found to be 3.3+/-1.5mm and 5.8+/-2.9mm for femoral and tibial/fibular attachment
      sites, respectively.

PMID- 27717546
TI  - Age and sex alone are insufficient to predict human rib structural response to
      dynamic A-P loading.
AB  - Thoracic injuries from motor vehicle crashes (MVCs) are common in children and
      the elderly and are associated with a high rate of mortality for both groups. Rib
      fractures, in particular, are linked to high mortality rates which increase with
      the number of fractures sustained. Anthropomorphic test devices (ATDs) and
      computational models have been developed to improve vehicle safety, however these
      tools are constructed based on limited physical datasets. To-date, no study has
      explored variation of rib structural properties across the entire age spectrum
      with data obtained using the same experimental methodology to allow for
      comparison. One-hundred eighty-four ribs from 93 post mortem human subjects
      (PMHS) (70 male, 23 female; ages 4-99) were subjected to dynamic bending tests
      simulating a frontal impact to the thorax. Structural mechanical properties were
      calculated and a multi-level statistical model quantified the sample variance as
      explained by age and sex. Displacement (deltaX), peak force (Fpeak), linear
      structural stiffness (K), energy absorption to fracture (Utot), and plastic
      properties including post-yield energy absorption (UPl), plastic displacement
      (deltaPl), and the ratio of elastic to secant stiffness (K-ratio) all showed
      negative relationships with age, while only Fpeak, K, and Utot were dependent on
      sex. Despite these relationships being statistically significant, only 7-39% of
      variance is explained by age and only 3-17% of variance is explained by sex. This
      demonstrates that variability in bone properties is more complex than simply
      chronological age- and sex-dependence and should be explored in the context of
      biological mechanisms instead.

PMID- 27717548
TI  - An evolutionary model of osteoarthritis including articular cartilage damage, and
      bone remodeling in a computational study.
AB  - With osteoarthritis, a complex set of progressive chemical, biological, and
      mechanical changes occur in both cartilage and bone. The aim of this study is to
      develop a high-fidelity computational model of the complete bone-cartilage unit
      to study the evolution of osterarthritis-induced articular cartilage (AC) damage
      and remodeling of subchondral cortical bone (SCB) and subchondral trabecular bone
      (STB). A finite element model of spherical indentation was developed with a depth
      dependent anisotropic model of degenerating articular cartilage, a calcified
      cartilage (CC) zone, and SCB and STB remodeling regions. Calcified tissue (CC,
      SCB, and STB) and AC material regions were integrated to form an evolutionary
      bone-cartilage unit model. Results indicate that with indentation loading,
      articular cartilage damage occurs at the articular surface. Furthermore, bone
      remodeling was predicted to occur with a net stiffening of the subchondral bone
      plate. Changes in indentation force were minimal (<2%) between initial and final
      peak indentation loading. However, additional degradation and wear of AC and/or
      alterations in loading may have more pronounced effects on the mechanical
      response of the bone-cartilage unit. Bone remodeling and articular cartilage
      damage predictions are consistent with experimental observations that cartilage
      damage begins at the articular surface and subchondral bone experiences a
      thickening (i.e., stiffening) response with osteoarthritis. Our results provide
      insight into the early-term initiation behavior of osteoarthritis; the potential
      consequences of evolutions in AC, SCB, and STB with disease progression; and may
      guide future experimental and computational studies to elucidate mechanisms of
      osteoarthritis progression.

PMID- 27717549
TI  - Hemodynamic modeling of leukocyte and erythrocyte transport and interactions in
      intracranial aneurysms by a multiphase approach.
AB  - Hemodynamics has been recognized as an important factor in the development,
      growth, and rupture of cerebral aneurysms, and investigated by computational
      fluid dynamics techniques using a single phase approach. However, flow-dependent
      cell transport and interactions are usually ignored in single phase models, in
      which blood is usually treated as a single phase Newtonian fluid. For getting
      better insight into the underlying pathology of intracranial aneurysm, cell
      transport and interactions should be covered in hemodynamic studies. In the
      present study, a multiphase hemodynamic model incorporating cell transport and
      interactions was developed, in which blood was modeled as multiphase fluid having
      a continuous phase (plasma) and two particulate phases (erythrocytes and
      leukocytes). The model showed good agreement with experimental data and
      observations in the literature, and was applied to four patient-specific
      aneurysms in a pulsatile manner. Leukocyte accumulations were predicted at
      locations with flow disturbance and low wall shear stress. The concentrations of
      leukocyte at accumulation sites were found to exceed 200 to 500% of normal
      physiological level on three unstable aneurysms, including two ruptured aneurysms
      and a growing aneurysm where accumulation was observed near a daughter sac and a
      secondary aneurysm. This suggested that aneurysms with complex secondary flow
      patterns could be prone to leukocyte accumulation on the wall. As this is the
      first study to characterize cell transport and interactions in aneurysm
      hemodynamics, our model can serve as a foundation for future intracranial
      aneurysm models.

PMID- 27717550
TI  - Science in Focus: Circulating Tumour DNA as a Liquid Biopsy.

PMID- 27717551
TI  - Supplementation of freezing and thawing media with brain-derived neurotrophic
      factor protects human sperm from freeze-thaw-induced damage.
AB  - OBJECTIVE: To investigate the effects of brain-derived neurotrophic factor (BDNF)
      supplementation to freezing and thawing media on frozen-thawed human sperm
      parameters. DESIGN: Laboratory study. SETTING: University hospital. PATIENT(S):
      Semen samples from 21 healthy fertile men. INTERVENTION(S): We measured reactive
      oxygen species (ROS) by flow cytometry using the probes dichlorofluorescin
      diacetate for intracellular hydrogen peroxide (H2O2) and dihydroethidium for
      intracellular superoxide anion (O2-*), sperm plasma membrane integrity by flow
      cytometry, caspase-3 activity using ELISA, and AKT phosphorylation status using
      Western blot in sperm that was cryopreserved and thawed in media either
      supplemented with BDNF or without BDNF supplementation (control). MAIN OUTCOME
      MEASURE(S): Sperm motility, viability, ROS levels, caspase-3 activity and AKT
      phosphorylation. RESULT(S): The percentage of motile and viable sperm cells was
      significantly higher in BDNF-supplemented groups as compared with the
      nonsupplemented (control) group. There was a significant difference in AKT
      phosphorylation status between BDNF-supplemented groups and the control group.
      Moreover, the levels of intracellular H2O2 and caspase-3 activity were
      significantly lower in the sperm cells that were frozen and thawed in media
      supplemented with BDNF compared with in the control group. CONCLUSION(S): BDNF
      supplementation to sperm freezing or thawing media has protective effects against
      oxidative stress and apoptosis in frozen-thawed human spermatozoa and could
      improve sperm function, probably through the activation of AKT.

PMID- 27717553
TI  - New developments in long-acting reversible contraception: the promise of
      intrauterine devices and implants to improve family planning services.
AB  - After decades of having the developed world's highest rates of unintended
      pregnancy, the United States finally shows signs of improvement. This progress is
      likely due in large part to increased use of highly effective long-acting
      reversible methods of contraception. These methods can be placed and do not
      require any maintenance to provide years of contraception as effective as
      sterilization. Upon removal, fertility returns to baseline rates. This article
      addresses advances in both software-improved use and elimination of barriers to
      provide these methods; and hardware-novel delivery systems and devices.

PMID- 27717552
TI  - Evaluation of an ultra-low-dose oral contraceptive for dysmenorrhea: a placebo
      controlled, double-blind, randomized trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of an ultra-low-dose oral
      contraceptive (NPC-01; 0.02 mg ethinyl estradiol and 1 mg norethisterone) in
      subjects with dysmenorrhea. DESIGN: Placebo-controlled, double-blind, randomized
      trial. SETTING: Clinical trial sites. PATIENT(S): Two hundred fifteen subjects
      with dysmenorrhea. INTERVENTION(S): Subjects were randomly assigned to receive
      NPC-01, placebo, or IKH-01 (0.035 mg ethinyl estradiol and 1 mg norethisterone)
      for four cycles. MAIN OUTCOME MEASURE(S): Total dysmenorrhea score (verbal rating
      scale) assessing pain on the basis of limited ability to work and need for
      analgesics. RESULT(S): The reductions of total dysmenorrhea score and visual
      analog scale score after the treatment were significantly higher in the NPC-01
      group than in the placebo group. Furthermore, the efficacy of NPC-01 was
      comparable to that of IKH-01. The overall incidence of side effects was
      significantly higher in the NPC-01 group than in the placebo group. All side
      effects that occurred in the NPC-01 group were previously reported in patients
      receiving IKH-01. No serious side effects occurred. CONCLUSION(S): The ultra-low
      dose contraceptive NPC-01 relieved dysmenorrhea as effectively as IKH-01. Thus,
      NPC-01 could represent a new option for long-term treatment of dysmenorrhea.
      CLINICAL TRIAL IDENTIFICATION NUMBER: NCT01129102.

PMID- 27717554
TI  - Effect of first line cancer treatment on the ovarian reserve and follicular
      density in girls under the age of 18 years.
AB  - OBJECTIVE: To study the impact of first-line antineoplastic treatment on ovarian
      reserve in young girls returning for ovarian tissue cryopreservation (OTC) in
      connection with a relapse. DESIGN: Retrospective case-control study. SETTING:
      University hospitals. PATIENT(S): Sixty-three girls under the age of 18 years who
      underwent OTC before (group 1: 31 patients) and after (group 2: 32 patients)
      their initial cancer treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Follicular densities (follicles/mm3) measured from an ovarian cortical biopsy
      before OTC. The ovarian volume (mL) of entire ovaries excised for OTC was also
      monitored. RESULT(S): There was no statistically significant difference in the
      mean age or follicular density between groups 1 and 2 (334 +/- 476/mm3 vs. 327 +/
      756/mm3). In contrast, the ovarian volume and total number of ovarian cortex
      chips cryopreserved were statistically significantly lower in patients who
      received gonadotoxic treatment before OTC (mean +/- standard deviation [SD]:
      ovarian volume, 5.3 +/- 3.1 mL vs. 2.9 +/- 2.1 mL, respectively; number of cortex
      chips: 21.3 +/- 8.1 vs. 15.2 +/- 7.1, respectively). The reduction in the
      estimated ovarian reserve ranged from 10% to 20% in children to around 30% in
      adolescent girls (>10 years). CONCLUSION(S): Girls under the age of 10 tolerate a
      gonadotoxic insult better than adolescents, who may experience up to a 30%
      reduction in the ovarian reserve via first-line gonadotoxic treatment, which at
      present is considered to have little effect on the follicle pool. This
      information will improve counseling of young female cancer patients in deciding
      whether to undergo fertility preservation treatment.

PMID- 27717556
TI  - Erratum.

PMID- 27717555
TI  - Establishing reference values for age-related spermatogonial quantity in
      prepubertal human testes: a systematic review and meta-analysis.
AB  - OBJECTIVE: To collect published data on spermatogonial quantity in the testes of
      healthy children and calculate the reference values of spermatogonial quantities
      throughout prepuberty. DESIGN: Systematic literature search in PubMed and EMBASE
      focusing on the number of spermatogonia per transverse tubular cross section
      (S/T) and spermatogonial density per cubic centimeter (cm3) of testicular volume
      (S/V) throughout prepuberty. SETTING: None. PATIENT(S): None. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Polynomial meta-regression analyses of S/T and S/V
      of healthy boys from the ages of 0 to 14 years. RESULT(S): We found six papers
      describing original quantitative data on S/T and S/V of healthy boys (total n =
      334 and 62, respectively) that were suitable for meta-analysis. Polynomial meta
      regression analyses of S/T and S/V demonstrated a clear pattern of spermatogonial
      quantity throughout prepubertal life. This consisted of a decline during the
      first 3 years of life, a gradual increase until the ages of 6 to 7 years, a
      plateau until the age of 11 years, and a sharp incline reaching pubertal numbers
      at 13 to 14 years of age. The association between S/T and S/V allowed us to
      perform S/T to S/V extrapolation, creating reference S/V (rS/V) values throughout
      prepubertal life from a cohort of 372 boys. CONCLUSION(S): Spermatogonial
      quantity varies during testicular development toward puberty. The values found in
      this study may serve as a baseline clinical reference to study the impact of
      diseases and adverse effects of gonadotoxic treatments on spermatogonial quantity
      in prepubertal testes. Spermatogonial quantity reference values may also help to
      evaluate the quality of testicular biopsy samples acquired for fertility
      preservation of prepubertal boys.

PMID- 27717557
TI  - Expression of katanin p80 in human spermatogenesis.
AB  - OBJECTIVE: To define the stage-by-stage expression of KATNB1 during human
      spermatogenesis. DESIGN: Gene expression analysis, histologic and
      immunohistochemical evaluation. SETTING: University research laboratories and
      andrological clinic. PATIENT(S): Eighty human testicular biopsy samples: 43
      showing normal spermatogenesis, 9 with maturation arrest at level of
      spermatocytes, 8 with maturation arrest at level of spermatogonia, and 20 with a
      Sertoli cell only syndrome. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Evaluation of katanin p80 expression in normal as well as impaired
      spermatogenesis on mRNA (RT-PCR, RT-qPCR, and in situ hybridization) and protein
      level (immunohistochemistry/immunofluorescence). RESULT(S): KATNB1 messenger RNA
      is exclusively expressed in germ cells, and quantitatively reduced in maturation
      arrests at the level of spermatogonia. The KATNB1 protein was detected in type B
      spermatogonia entering meiosis and in the Golgi complex of pachytene
      spermatocytes. Immediately before the first meiotic division, it is colocalized
      with the cleaving centriole. It was also detected in early round spermatids in
      the dictyosome. CONCLUSION(S): The expression and localization of KATNB1 support
      a role in spindle formation. The localization of KATNB1 in early round spermatids
      suggests an involvement in the formation of microtubule-based structures during
      spermiogenesis (manchette and flagellum). These data are consistent with the
      demonstrated role of KATNB1 in mouse meiosis, nuclear shaping, and flagellum
      formation of sperm and suggest the strong conservation of function even between
      distantly related species.

PMID- 27717560
TI  - Biofouling and control approaches in membrane bioreactors.
AB  - Membrane fouling (especially biofouling) as a critical issue during membrane
      reactor (MBR) operation has attracted much attention in recent years. Although
      previous review papers have presented different aspects of MBR's fouling when
      treating various wastewaters, the information related to biofouling in MBRs has
      only simply or partially reviewed. This work attempts to give a more
      comprehensive and elaborate explanation of biofilm formation, biofouling factors
      and control approaches by addressing current achievements. This also suggests to
      a better way in controlling biofouling by developing new integrated MBR systems,
      novel flocculants and biomass carriers.

PMID- 27717559
TI  - Peritoneum and omentum are natural reservoirs for chondrocytes of osteochondral
      autografts: A comparative animal study.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of the
      omentum, peritoneum, paratenon and skeletal muscle on the proliferation of the
      cartilage tissue using rabbit model as an in vivo culture medium. METHODS: 6
      months old forty-five New Zealand rabbits were randomized into omentum,
      peritoneum, muscle, and Achilles paratenon groups. Standard sized osteochondral
      grafts were harvested from right knees and immediately placed into the specified
      tissues. Control group was fresh cartilage at the end of follow-up. After five
      months, samples were collected and evaluated macroscopically by measuring their
      dimensions (vertical = D1, horizontal = D2, and depth = D3) and volumes, and
      histologically by counting the chondrocyte number using camera lucida method.
      RESULTS: Macroscopically, increase in mean values for D1 and D2 dimensions of
      specimens from paratenon and omentum compared to pretransplant dimensions was
      statistically significant (p < 0.05). Although, volume measurements were higher
      in omentum and peritoneum group compared to pretransplant dimensions, increase
      was not significant (p > 0.05). Histologically, mean chondrocyte count was 14.0
      +/- 0.6 in fresh articular cartilage. Mean chondrocyte counts were 14.4 +/- 0.9
      in omentum group, 15.4 +/- 1.0 in peritoneum group, 9.7 +/- 1.3 in muscle group
      and 9.2 +/- 0.4 in Achilles paratenon group respectively. However, mean
      chondrocyte counts were higher in samples of omentum and peritoneum group
      compared to fresh articular cartilage, increase was not statistically significant
      (p > 0.05). DISCUSSION: Transplantation of the cartilage grafts into mesothelium
      enhanced the chondrocyte counts and volumes compared with the pretransplant
      measurements. Mesothelium may have the potential to be used as an in vivo culture
      medium for osteochondral tissue growth.

PMID- 27717562
TI  - Opioids and overdoses: Time to get serious; time to get sensible.

PMID- 27717561
TI  - Microbial community structure of different electrode materials in constructed
      wetland incorporating microbial fuel cell.
AB  - The microbial fuel cell coupled with constructed wetland (CW-MFC) microcosms were
      operated under fed-batch mode for evaluating the effect of electrode materials on
      bioelectricity generation and microbial community composition. Experimental
      results indicated that the bioenergy output in CW-MFC increased with the
      substrate concentration; maximum average voltage (177mV) was observed in CW-MFC
      with carbon fiber felt (CFF). In addition, the four different materials resulted
      in the formation of significantly different microbial community distribution
      around the anode electrode. The relative abundance of Proteobacteria in CFF and
      foamed nickel (FN) was significantly higher than that in stainless steel mesh
      (SSM) and graphite rod (GR) samples. Notably, the findings indicate that CW-MFC
      utilizing FN anode electrode could apparently improve relative abundance of
      Dechloromonas, which has been regarded as a denitrifying and phosphate
      accumulating microorganism.

PMID- 27717563
TI  - Management of recurrent aphthous ulcers using low-level lasers: A systematic
      review.
AB  - BACKGROUND AND OBJECTIVE: The exact etiology of recurrent aphthous ulcers (RAS)
      is unknown. The management of RAS is not always straightforward. The aim of this
      review is to critically analyze and summarize the clinical literature focusing on
      the management of aphthous ulcers using low-level lasers. MATERIALS AND METHODS:
      The Medline (PubMed), Web of Knowledge (ISI), Cochrane Central Register of
      Controlled Trials (CENTRAL) and Embase databases were searched electronically for
      studies published in last 20 years (1995-2015) using the keywords "recurrent
      aphthous stomatitis," "aphthous ulcers," and "laser." RESULTS: A total of 85
      articles were found during the initial search; 76 studies were excluded for not
      fulfilling the criteria whereas nine studies were deemed suitable for this
      review. Among the included studies, two articles were case reports and seven were
      randomized clinical trials. Study design, sample size, type of intervention and
      control of each study were critically analyzed and summarized according to the
      CONSORT protocol. In majority of the patients, immediate pain relief and
      accelerated ulcer healing was observed following irradiation with lasers.
      CONCLUSIONS: Although various types of lasers have succeeded in providing
      immediate pain relief to patients, carbon dioxide (CO2) lasers have the unique
      advantage of requiring a short exposure time (5-10s). In order to ascertain the
      efficacy of laser for treating ulcers in the clinical setting, more clinical
      trials are required.

PMID- 27717558
TI  - Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with
      chronic rhinosinusitis with nasal polyps: Possible role of the nongastric H,K
      ATPase.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is often
      characterized by tissue eosinophilia that is associated with poor prognosis.
      Recent findings that proton pump inhibitors (PPIs) directly modulate the
      expression of eotaxin-3, an eosinophil chemoattractant, in patients with
      eosinophilic diseases suggest therapeutic potential for PPIs in those with
      CRSwNP. OBJECTIVE: We assessed the effect of type 2 mediators, particularly IL-13
      and eotaxin-3, on tissue eosinophilia and disease severity in patients with
      chronic rhinosinusitis (CRS). Further investigation focused on PPI suppression of
      eotaxin-3 expression in vivo and in vitro, with exploration of underlying
      mechanisms. METHODS: Type 2 mediator levels in nasal tissues and secretions were
      measured by using a multiplex immunoassay. Eotaxin-3 and other chemokines
      expressed in IL-13-stimulated human sinonasal epithelial cells (HNECs) and BEAS
      2B cells with or without PPIs were assessed by using ELISA, Western blotting,
      real-time PCR, and intracellular pH imaging. RESULTS: Nasal tissues and
      secretions from patients with CRSwNP had increased IL-13, eotaxin-2, and eotaxin
      3 levels, and these were positively correlated with tissue eosinophil cationic
      protein levels and radiographic scores in patients with CRS (P < .05). IL-13
      stimulation of HNECs and BEAS-2B cells dominantly induced eotaxin-3 expression,
      which was significantly inhibited by PPIs (P < .05). Patients with CRS taking
      PPIs also showed lower in vivo eotaxin-3 levels compared with those without PPIs
      (P < .05). Using intracellular pH imaging and altering extracellular K+, we found
      that IL-13 enhanced H+,K+-exchange, which was blocked by PPIs and the
      mechanistically unrelated H,K-ATPase inhibitor, SCH-28080. Furthermore, knockdown
      of ATP12A (gene for the nongastric H,K-ATPase) significantly attenuated IL-13
      induced eotaxin-3 expression in HNECs. PPIs also had effects on accelerating IL
      13-induced eotaxin-3 mRNA decay. CONCLUSION: Our results demonstrated that PPIs
      reduce IL-13-induced eotaxin-3 expression by airway epithelial cells.
      Furthermore, mechanistic studies suggest that the nongastric H,K-ATPase is
      necessary for IL-13-mediated epithelial responses, and its inhibitors, including
      PPIs, might be of therapeutic value in patients with CRSwNP by reducing
      epithelial production of eotaxin-3.

PMID- 27717565
TI  - Patient safety improvement interventions in children's surgery: A systematic
      review.
AB  - BACKGROUND: Adult surgical patient safety literature is plentiful; however, there
      is a disproportionate paucity of published safety work in the children's surgical
      literature. We sought to systematically evaluate the nature and quality of
      patient safety evidence pertaining to pediatric surgical practice. METHODS:
      Systematic search of MEDLINE and EMBASE databases and gray literature identified
      1399 articles. Data pertaining to demographics, methodology, interventions, and
      outcomes were extracted. Study quality was assessed utilizing formal criteria.
      RESULTS: 20 studies were included. 14 (70%) comprised peer-reviewed articles. 18
      (90%) were published in the last 4years. 13 (65%) described a novel intervention,
      and 7 (35%) described a modification of an existing intervention. Median patient
      sample size was 79 (29-1210). A large number (n=55) and variety (n=35) of
      measures were employed to evaluate the effect of interventions on patient safety.
      15 (75%) studies utilized a checklist tool as a component of their intervention.
      9 (45%) studies [comprising handoff tools (n=7); checklists (n=1); and
      multidimensional quality improvement initiatives (n=1)] reported a positive
      effect on patient safety. Quality assessment was undertaken on 14 studies.
      Quantitative studies had significantly higher quality scores than qualitative
      studies (61 [0-89] vs 44 [11-78], p=0.03). CONCLUSIONS: Pediatric surgical
      patient safety evidence is in its early stages. Successful interventions that we
      identified were typically handoff tools. There now ought to be an onus on
      pediatric surgeons to develop and apply bespoke pediatric surgical safety
      interventions and generate an evidence base to parallel the adult literature.
      LEVEL OF EVIDENCE: Level IV, Case series with no comparison group.

PMID- 27717564
TI  - Prospective validation of the shock index pediatric-adjusted (SIPA) in blunt
      liver and spleen trauma: An ATOMAC+ study.
AB  - BACKGROUND: Age-adjusted pediatric shock index (SIPA) does not require knowledge
      of age-adjusted blood pressure norms, yet correlates with mortality, serious
      injury, and need for transfusion in trauma. No prospective studies support its
      validity. METHODS: A multicenter prospective observational study of patients 4
      16years presenting April 2013-January 2016 with blunt liver and/or spleen injury
      (BLSI). SIPA (maximum heart rate/minimum systolic blood pressure) thresholds of
      >1.22, >1.0, and >0.9 in the emergency department were used for 4-6, 7-12 and 13
      16year-olds, respectively. Patients with ISS <=15 were excluded to conform to the
      original paper. Discrimination outcomes were compared between SIPA and shock
      index (SI). RESULTS: Of 1008 patients, 386 met inclusion. SI was elevated in 321,
      and SIPA elevated in 282. The percentage of patients with elevated index (SI or
      SIPA) and blood transfusion within 24 hours (30% vs 34%), BLSI grade >=3
      requiring transfusion (28% vs 32%), operative intervention (14% vs 16%) and ICU
      admission (64% vs 67%) was higher in the SIPA group. CONCLUSION: SIPA was
      validated in this multi-institutional prospective study and identified a higher
      percentage of children requiring additional resources than SI in BLSI patients.
      SIPA may be useful for determining necessary resources for injured patients with
      BLSI. LEVEL OF EVIDENCE: Level II prognosis.

PMID- 27717567
TI  - A new-generation 3D ozone FACE (Free Air Controlled Exposure).
AB  - To artificially simulate the impacts of ground-level ozone (O3) on vegetation,
      ozone FACE (Free Air Controlled Exposure) systems are increasingly recommended.
      We describe here a new-generation, three-dimensional ozone FACE, with O3
      diffusion through laser-generated micro-holes, pre-mixing of air and O3, O3
      generator with integral oxygen generator, continuous (day/night) exposure and
      full replication. Based on three O3 levels and assumptions on the pre-industrial
      O3 levels, we describe principles to calculate relative yield/biomass and
      estimate impacts even at lower-than-ambient O3 levels. The case study is called
      FO3X, and is at present the only ozone FACE in Mediterranean climate and one of
      the very few ozone FACEs investigating more than one stressor at a time. The
      results presented here will give further impulse to the research on O3 impacts on
      vegetation all over the world.

PMID- 27717566
TI  - Retroperitoneoscopic assisted single-site pyeloplasty using EZ access in
      children: Comparison with open dismembered pyeloplasty.
AB  - PURPOSE: The aim of this study was to compare the results of the
      retroperitoneoscopic assisted pyeloplasty (RASP) using EZ access (silicone rubber
      cap) with open dismembered pyeloplasty (ODP) in children. METHODS: A
      retrospective review was performed of patients treated for ureteropelvic junction
      (UPJ) obstruction with either RASP or ODP from 2010 to 2015. For patients with
      RASP, two 5-mm trocars were placed in the EZ access. The UPJ was dissected
      retroperitoneoscopically and dismembered pyeloplasty was performed
      extracorporeally. Patient demographics and operative outcomes were compared
      between the groups. RESULTS: A total of 50 children were included, with 25 RASP
      and 25 ODP. Mean patient age was 49months in the RASP group and 53months in the
      ODP group. Perioperative outcomes, including operative time (185 vs 188min) and
      postoperative hospital stay (2.0 vs 2.2days), were similar between the two
      groups. Mean skin scar length (17 vs 34mm) was significantly smaller in the RASP
      group. The postoperative success rate (96% vs 100%) was not significantly
      different between the groups. CONCLUSIONS: The RASP represents a safe and
      effective single-site procedure in children. This procedure significantly reduces
      the skin scar length and has equivalent surgical outcomes to ODP. THE TYPE OF
      STUDY: Retrospective comparative study. LEVELS OF EVIDENCE: III.

PMID- 27717568
TI  - Hexadecane degradation of Pseudomonas aeruginosa NY3 promoted by glutaric acid.
AB  - For further understanding of the roles of small organic acids commonly produced
      during alkane degradation, glutaric acid was found to be effective for promoting
      hexadecane degradation by P. aeruginosa NY3. Our results demonstrated that the
      synchronous metabolism of glutaric acid could increase both the growth rates and
      hexadecane degradation ability of P. aeruginosa NY3. Glutaric acid was proved to
      be able to increase the ratios of the concentrations of NAD+ and NADH inside
      strain NY3 cells, and subsequently accelerated cell growth rates through
      improving electron respiration rates. All the results of the activities of
      hexadecane monooxygenase, the expression levels of alkB1 and alkB2 gens and the
      bioconversion rate of hexadecane to 1-hexadecanol were confirmed that coexistence
      of glutaric acid could greatly increase the reaction rate of the first step of
      enzymeticlly degradation of hexadecane into hexadecanol. This also explained the
      promotion mechanism of glutaric acid on hexadecane degradation by P. aeruginosa
      strain from a certain point of view for the first time.

PMID- 27717569
TI  - Phyto-rhizoremediation of polychlorinated biphenyl contaminated soils: An outlook
      on plant-microbe beneficial interactions.
AB  - Polychlorinated biphenyls (PCBs) are toxic chemicals, recalcitrant to
      degradation, bioaccumulative and persistent in the environment, causing adverse
      effects on ecosystems and human health. For this reason, the remediation of PCB
      contaminated soils is a primary issue to be addressed. Phytoremediation
      represents a promising tool for in situ soil remediation, since the available
      physico-chemical technologies have strong environmental and economic impacts.
      Plants can extract and metabolize several xenobiotics present in the soil, but
      their ability to uptake and mineralize PCBs is limited due to the recalcitrance
      and low bioavailability of these molecules that in turn impedes an efficient
      remediation of PCB-contaminated soils. Besides plant degradation ability,
      rhizoremediation takes into account the capability of soil microbes to uptake,
      attack and degrade pollutants, so it can be seen as the most suitable strategy to
      clean-up PCB-contaminated soils. Microbes are in fact the key players of PCB
      degradation, performed under both aerobic and anaerobic conditions. In the
      rhizosphere, microbes and plants positively interact. Microorganisms can promote
      plant growth under stressed conditions typical of polluted soils. Moreover, in
      this specific niche, root exudates play a pivotal role by promoting the biphenyl
      catabolic pathway, responsible for microbial oxidative PCB metabolism, and by
      improving the overall PCB degradation performance. Besides rhizospheric microbial
      community, also the endophytic bacteria are involved in pollutant degradation and
      represent a reservoir of microbial resources to be exploited for bioremediation
      purposes. Here, focusing on plant-microbe beneficial interactions, we propose a
      review of the available results on PCB removal from soil obtained combining
      different plant and microbial species, mainly under simplified conditions like
      greenhouse experiments. Furthermore, we discuss the potentiality of "omics"
      approaches to identify PCB-degrading microbes, an aspect of paramount importance
      to design rhizoremediation strategies working efficiently under different
      environmental conditions, pointing out the urgency to expand research
      investigations to field scale.

PMID- 27717570
TI  - A hybrid monitoring and modelling approach to assess the contribution of sources
      of glyphosate and AMPA in large river catchments.
AB  - Large river catchments with mixed land use capture pesticides from many sources,
      and degradable pesticides are converted during downstream transport. Unravelling
      the contribution of pesticide source and the effect of degradation processes is a
      challenge in such areas. However, insight and understanding of the sources is
      important for targeted management, especially when water is abstracted from the
      river for drinking water production. The river Meuse is such a case. A long-term
      monitoring data set was applied in a modelling approach for assessing the
      contribution of waste water treatment plants (WWTPs) and tributaries (sub-basins)
      to surface water contamination, and to evaluate the effect of decay on the
      downstream concentrations of glyphosate and AMPA at the point of drinking water
      abstraction. The results show that WWTPs are important contributors for
      glyphosate and AMPA in large river catchments with mixed land uses. In the
      studied area, the river Meuse in the Netherlands, the relative contribution of
      WWTP effluents is above 29% for glyphosate and around 12% for AMPA. Local
      industries are found to be potentially big contributors of AMPA. Glyphosate
      entering the river system is gradually converted to AMPA and other degradation
      productions, which results in downstream loads that are considerably lower than
      the sum of all influxes. In summer when the travel time is longer due to lower
      discharge, the first order decay of glyphosate in the river Meuse is estimated to
      result in about 50% reduction of the downstream glyphosate concentrations over a
      river stretch of 250km. The contribution of glyphosate decay to the observed AMPA
      concentrations ranges between 2% and 10%. Contributions are sensitive to seasonal
      variations in discharge that influence the concentrations through dilution and
      degradation.

PMID- 27717571
TI  - Automated detection of atrial fibrillation using R-R intervals and multivariate
      based classification.
AB  - Automated detection of AF from the electrocardiogram (ECG) still remains a
      challenge. In this study, we investigated two multivariate-based classification
      techniques, Random Forests (RF) and k-nearest neighbor (k-nn), for improved
      automated detection of AF from the ECG. We have compiled a new database from ECG
      data taken from existing sources. R-R intervals were then analyzed using four
      previously described R-R irregularity measurements: (1) the coefficient of sample
      entropy (CoSEn), (2) the coefficient of variance (CV), (3) root mean square of
      the successive differences (RMSSD), and (4) median absolute deviation (MAD).
      Using outputs from all four R-R irregularity measurements, RF and k-nn models
      were trained. RF classification improved AF detection over CoSEn with overall
      specificity of 80.1% vs. 98.3% and positive predictive value of 51.8% vs. 92.1%
      with a reduction in sensitivity, 97.6% vs. 92.8%. k-nn also improved specificity
      and PPV over CoSEn; however, the sensitivity of this approach was considerably
      reduced (68.0%).

PMID- 27717572
TI  - Massive J-waves in the context of intracranial hemorrhage.
AB  - Transient ST-segment elevation may be caused by conditions other than myocardial
      ischemia, among them intracranial hemorrhage. Recognition of the underlying
      etiology of these ST-segment changes is key because of the vastly different
      therapies used to treat them. We describe the case of a patient with massive
      transient J-waves and ST-segment elevation in the context of an intracranial
      hemorrhage.

PMID- 27717573
TI  - Mercury in the ecosystem of Admiralty Bay, King George Island, Antarctica:
      Occurrence and trophic distribution.
AB  - Mercury (Hg) can reach the environment through natural and human-related sources,
      threatening ecosystems all over the planet due to its well known deleterious
      effects. Therefore, Antarctic trophic webs, despite being relatively isolated,
      are not exempt of its influence. To evaluate Hg concentrations in an Antarctic
      ecosystem, different tissues from 2 species of invertebrates, 2 of fish, 8 of
      birds, 4 of pinnipeds and at least 5 of vegetation were investigated (n=176). For
      animals, values ranged from 0.018 to 48.7MUgg-1 dw (whole Antarctic krill and
      Antarctic Fur Seal liver). They were generally correlated to trophic position
      (assessed by delta15N and delta13C) but also to cephalopods and myctophids
      consumption. For vegetation, values ranged from 0.014 to 0.227MUgg-1 dw
      (Colobanthus quitensis and an unidentified lichen), with lichens presenting
      significantly higher values than mosses, likely due to year-round exposure and
      absorption of animal derived organic matter, as hypothesized by literature.

PMID- 27717574
TI  - Occurrence of plastic debris in the stomach of the invasive crab Eriocheir
      sinensis.
AB  - The Chinese mitten crab is known as a pest causing damage to fishing gears and
      fish. On the other hand, this highly invasive species is considered a delicacy by
      Asian migrants and therefore commercially fished and sold in many countries. The
      ingestion of plastic by the Chinese mitten crab Eriocheir sinensis from the
      Baltic coastal waters (Poland) and the Tagus Estuary (Portugal) was studied based
      on stomach content analysis. As many as 13% of the 302 analysed males and females
      (38.07-89.07mm carapace width) from both regions, contained microplastic in the
      form of strands and balls. Most of them were transparent. Ingested plastic
      particles were identified as fragments of fishing gears. Contamination with
      plastic may have a negative impact on this species as well as on higher trophic
      levels feeding on crabs.

PMID- 27717575
TI  - Modeling and evaluation of the oil-spill emergency response capability based on
      linguistic variables.
AB  - An evaluation of the oil-spill emergency response capability (OS-ERC) currently
      in place in modern marine management is required to prevent pollution and loss
      accidents. The objective of this paper is to develop a novel OS-ERC evaluation
      model, the importance of which stems from the current lack of integrated
      approaches for interpreting, ranking and assessing OS-ERC performance factors. In
      the first part of this paper, the factors influencing OS-ERC are analyzed and
      classified to generate a global evaluation index system. Then, a semantic tree is
      adopted to illustrate linguistic variables in the evaluation process, followed by
      the application of a combination of Fuzzy Cognitive Maps (FCM) and the Analytic
      Hierarchy Process (AHP) to construct and calculate the weight distribution.
      Finally, considering that the OS-ERC evaluation process is a complex system, a
      fuzzy comprehensive evaluation (FCE) is employed to calculate the OS-ERC level.
      The entire evaluation framework obtains the overall level of OS-ERC, and also
      highlights the potential major issues concerning OS-ERC, as well as expert
      opinions for improving the feasibility of oil-spill accident prevention and
      protection.

PMID- 27717576
TI  - Optimizing CT Pulmonary Angiogram Utilization in a Community Emergency
      Department: A Pre- and Postintervention Study.
AB  - PURPOSE: Optimizing the utilization of CT pulmonary angiogram (CTPA) for the
      diagnosis and workup of acute chest pain can provide an opportunity to reduce
      unnecessary radiation and health care system expense. METHODS: An attempt to
      improve CTPA utilization began by measuring overall department and clinician
      specific utilization. This was bolstered by retrospectively evaluating patient
      charts for pulmonary embolism scoring criteria and D-dimer utilization so as to
      better understand gaps in diagnostic workup. The department-wide and
      individualized metrics were then provided to each emergency department clinician
      and differences between the pre- and postintervention data were evaluated.
      RESULTS: The percentage of positive CTPAs did not change significantly at 8.7%
      and 9.2% in the pre- and postintervention groups, respectively. Similarly, the
      workup of patients based on retrospective PERC and Wells-score criteria did not
      significantly improve after the intervention. However, the percentage of CTPAs
      ordered on low D-dimer patients did decrease significantly post-intervention.
      Further observational analysis uncovered marked variability in clinician ordering
      behavior and diagnostic rates. CONCLUSIONS: Overall, such an intervention seems
      to have a limited, though not insignificant, impact on the workup of suspected
      pulmonary embolism. Calculating provider-specific utilization metrics allows both
      the radiologist and clinician to better understand opportunities to improve
      health care delivery.

PMID- 27717577
TI  - Role of Medical Physicists in the Diagnostic Residency Training Program.

PMID- 27717578
TI  - The Dubious Value of Coronary Calcium Scoring on Lung Cancer Screening CT.

PMID- 27717579
TI  - IVUS and OCT guided primary percutaneous coronary intervention for spontaneous
      coronary artery dissection with bioresorbable vascular scaffolds.
AB  - Spontaneous coronary artery dissection (SCAD) is an uncommon but important cause
      of acute coronary syndrome. The diagnosis of SCAD by an angiogram alone can be
      challenging and the increasing use of intracoronary imaging has proven an
      invaluable diagnostic adjunct in this regard. The appropriate initial management
      of SCAD has been a matter of significant debate. Owing to frequent spontaneous
      healing of coronary dissection and a higher risk of complications with
      percutaneous coronary intervention (PCI) in the setting of SCAD, a default
      approach of mechanical revascularization is not recommended. However in the
      presence of vessel occlusion and on-going myocardial infarction PCI is mandated.
      Bioresorbable vascular scaffolds (BVS) offer potential advantages over the
      conventional stents in the setting of SCAD. We describe a state-of-the-art
      approach to the acute treatment of SCAD causing STEMI, utilizing intravascular
      ultrasound (IVUS), optical coherence tomography (OCT) and BVS and discuss
      management strategies for the modern era.

PMID- 27717580
TI  - Transpedal approach for iliac artery stenting: A pilot study.
AB  - OBJECTIVE: To demonstrate the safety and feasibility of the transpedal approach
      as an alternate arterial access site for iliac artery intervention. BACKGROUND:
      The common femoral artery is the traditional access site for the endovascular
      treatment of iliac artery stenoses. However, this approach is associated with
      complication rates as high as 2%, including retroperitoneal bleeding which
      carries high patient morbidity and mortality. Furthermore, the standard femoral
      approach is associated with longer recovery times and longer time to ambulation
      which are important considerations especially when performing procedures in an
      ambulatory setting. METHODS: Twelve patients were prospectively followed after
      treatment for symptomatic iliac artery stenosis via transpedal access. Under
      ultrasound guidance, one of the pedal arteries was visualized and accessed, and
      stenting of the iliac arteries were performed as per protocol. The patient was
      monitored immediately post procedure and clinical follow up was performed at one
      week and one month later. RESULTS: The average age of the patients was 71years
      old. 58% were male. Most patients had Rutherford class III symptoms. Successful
      stent placement was achieved in all 12 patients via transpedal access. No
      conversion to femoral access was required. No complications immediately post
      procedure nor at any time period during follow up were noted. Lower extremity
      arterial duplex at one month showed patent stents and patent pedal access site
      vessels in all patients. CONCLUSION: Transpedal arterial access may be a safe and
      feasible approach for iliac artery stenting. Given the possible benefits of
      avoiding femoral artery access, larger studies should be conducted directly
      comparing the different approaches.

PMID- 27717581
TI  - Establishing the ACORN National Practitioner Database: Strategies to Recruit
      Practitioners to a National Practice-Based Research Network.
AB  - OBJECTIVES: The purpose of this paper is to report on the recruitment and
      promotion strategies employed by the Australian Chiropractic Research Network
      (ACORN) project aimed at helping recruit a substantial national sample of
      participants and to describe the features of our practice-based research network
      (PBRN) design that may provide key insights to others looking to establish a
      similar network or draw on the ACORN project to conduct sub-studies. METHODS: The
      ACORN project followed a multifaceted recruitment and promotion strategy drawing
      on distinct branding, a practitioner-focused promotion campaign, and a
      strategically designed questionnaire and distribution/recruitment approach to
      attract sufficient participation from the ranks of registered chiropractors
      across Australia. RESULTS: From the 4684 chiropractors registered at the time of
      recruitment, the project achieved a database response rate of 36% (n = 1680),
      resulting in a large, nationally representative sample across age, gender, and
      location. This sample constitutes the largest proportional coverage of
      participants from any voluntary national PBRN across any single health care
      profession. CONCLUSIONS: It does appear that a number of key promotional and
      recruitment features of the ACORN project may have helped establish the high
      response rate for the PBRN, which constitutes an important sustainable resource
      for future national and international efforts to grow the chiropractic evidence
      base and research capacity. Further rigorous enquiry is needed to help evaluate
      the direct contribution of specific promotional and recruitment strategies in
      attaining high response rates from practitioner populations who may be invited to
      participate in future PBRNs.

PMID- 27717582
TI  - Glucuronide and sulfate conjugates of tetrabromobisphenol A (TBBPA): Chemical
      synthesis and correlation between their urinary levels and plasma TBBPA content
      in voluntary human donors.
AB  - 3,3',5,5'-Tetrabromobisphenol-A (TBBPA) is an important brominated flame
      retardant in epoxy, vinyl esters and polycarbonate resins. Previous studies have
      already shown the occurrence of its Phase II metabolites, TBBPA-glucuronide and
      sulfate conjugates, in human urine, after oral administration of TBBPA. The main
      objective of this work is to examine correlations among level of TBBPA in human
      blood and those of its Phase II metabolites in human urine. Four water-soluble
      TBBPA conjugates were synthesized, purified and characterized. An analytical
      protocol using solid-phase extraction and liquid chromatography-electrospray
      tandem mass spectrometry (SPE-LC-MS/MS) quantification was developed for the
      simultaneous analysis of these glucuronide and sulfate conjugates in human urine
      samples. TBBPA and its Phase II metabolites in paired human plasma and urine
      samples collected randomly from 140 voluntary donors in Hong Kong SAR, China,
      were determined. One or more TBBPA conjugates were detected in all of the urine
      samples, with concentration ranging from 0.19 to 127.24MUgg-1-creatinine. TBBPA
      was also quantified in >85% of the plasma and urine samples. Strong correlations
      were observed between TBBPA content in plasma and the total amount of TBBPA
      related compounds in urine.

PMID- 27717583
TI  - [Febrile exanthema in French Guyana].

PMID- 27717584
TI  - Parkinson's disease: SNCA-, PARK2-, and LRRK2- targeting microRNAs elevated in
      cingulate gyrus.
AB  - INTRODUCTION: In order to better understand the role of epigenetic influences in
      the etiology of Parkinson's disease (PD), we studied the expression of microRNAs
      in gyri cinguli of patients and controls. METHODS: Expression profiling of 744
      well-characterized microRNAs in gyri cinguli from patients and controls using
      TaqMan array microRNA cards. Verification of significantly dysregulated microRNAs
      by SYBR Green qRT-PCR. RESULTS: First screen by TaqMan array identified 43
      microRNAs that were upregulated in gyri cinguli from patients. Of those
      microRNAs, 13 are predicted to regulate at least one of six genes mutated in
      monogenic forms of PD (DJ-1, PARK2, PINK1, LRRK2, SNCA, and HTRA2). Five of these
      13 microRNAs (-144, -199b, -221, -488, -544) were also found upregulated by SYBR
      Green qRT-PCR and are predicted to regulate either SNCA, PARK2, LRRK2 or
      combinations thereof. Consistently, expression of SNCA, PARK2, and LRRK2 was
      reduced in patients. An additional 5 out of ten potential target genes tested
      were downregulated. These are DRAM (DNA damage regulated autophagy modulator 1),
      predicted to be regulated by miR-144, EVC (Ellis Van Creveld Protein) by miR-221,
      ZNF440 (Zinc Finger Protein 440) by miR-199b, MTFMT (Mitochondrial Methionyl-tRNA
      Formyltransferase) by miR-488 and XIRP2 (Xin Actin Binding Repeat Containing)
      possibly controlled by miR-544a. CONCLUSION: The study identified five microRNAs
      that play a role in the etiology of Parkinson's disease likely by modifying
      expression of SNCA, PARK2, LRRK2 and additional genes required for normal
      cellular function.

PMID- 27717586
TI  - Termination of Persistent Hiccups by Digital Rectal Massage.

PMID- 27717585
TI  - High grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6:
      Double hit and triple hit lymphomas and double expressing lymphoma.
AB  - Diffuse large B-cell lymphomas with aberrations in MYC, BCL2 and/or BCL6 by
      genetic alterations or protein expression represent a group of high grade B-cell
      lymphomas with inferior outcomes when treated with standard RCHOP chemotherapy.
      As a result, intensified induction regimens have been suggested in an effort to
      improve outcomes. Conclusions to date have largely been drawn from retrospective
      data although prospective data is slowly starting to emerge. Chemoimmunotherapy
      refractoriness is problematic and relapse rates are high. Patients with double
      hit lymphoma appear to have increased risk of CNS involvement and prophylaxis is
      recommended. There is insufficient evidence available to date to strongly
      recommend for or against consolidative stem cell transplant in this population.
      Collaborative clinical trials will be needed to establish a preferred therapeutic
      regimen and an appropriate standard of care in this unique group of patients with
      DLBCL.

PMID- 27717587
TI  - Female with Diplopia.

PMID- 27717588
TI  - Onychomadesis: A Late Complication of Hand, Foot, and Mouth Disease.

PMID- 27717589
TI  - An Unusual Case of Postabortion Hemorrhage.

PMID- 27717590
TI  - Endotracheal Intubation after Acute Drug Overdoses: Incidence, Complications, and
      Risk Factors.
AB  - BACKGROUND: Drug overdose is the leading cause of injury-related fatality in the
      United States, and respiratory failure remains a major source of morbidity and
      mortality. OBJECTIVES: We aimed to identify the incidence and risk factors for
      endotracheal intubation after acute drug overdose. METHODS: This secondary data
      analysis was performed on a 5-year prospective cohort at two urban tertiary-care
      hospitals. The present study analyzed adult patients with suspected acute drug
      overdose to derive independent clinical predictors of endotracheal intubation.
      RESULTS: We analyzed 2497 patients with acute drug overdose, of whom 87 (3.5%)
      underwent endotracheal intubation. Independent clinical risk factors for
      endotracheal intubation were: younger age (odds ratio [OR] 0.97, 95% confidence
      interval [CI] 0.96-0.98), and history of obstructive lung disease (OR 6.6, 95% CI
      3.5-12.3); however, heart failure had no association. Patients with obstructive
      lung disease had significantly more hypercapnia (mean difference 6.8 mm Hg, 95%
      CI 2.3-11.3) and a higher degree of acidemia (mean pH difference 0.04, 95% CI
      0.01-0.07) than patients without obstructive lung disease. Lack of rapid sequence
      sedative/paralytic was associated with in-hospital fatality. Early complications
      of endotracheal intubation itself included desaturation (3.4%) and bradycardia
      (1%). CONCLUSIONS: Endotracheal intubation was infrequently performed on patients
      with acute drug overdose, and complications were rare when performed. Risk
      factors associated with endotracheal intubation included younger age and prior
      obstructive lung disease.

PMID- 27717591
TI  - Aortic Dissection: An Unusual Extraspinal Cause of Acute Paraplegia in the
      Emergency Department.

PMID- 27717592
TI  - Euglycemic Diabetic Ketoacidosis with Elevated Acetone in a Patient Taking a
      Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor.
AB  - BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a
      class of antihyperglycemic agents that increase urinary glucose excretion by
      interfering with the reabsorption of glucose in the proximal renal tubules. In
      May of 2015, the U.S. Food and Drug Administration released a warning concerning
      a potential increased risk of ketoacidosis and ketosis in patients taking these
      medications. CASE REPORT: We present a case of a 57-year-old woman with type 2
      diabetes mellitus taking a combination of canagliflozin and metformin who
      presented with progressive altered mental status over the previous 2 days. Her
      work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous
      serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose
      > 500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated
      serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was
      treated with intravenous insulin and fluids, and the metabolic abnormalities and
      her altered mental status resolved within 36 h. This was the first episode of
      diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN
      BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk
      for ketoacidosis. Due to the renal glucose-wasting properties of these drugs,
      they may present with ketoacidosis with only mild elevations in serum glucose,
      potentially complicating the diagnosis. Acetone is one of the three main ketone
      bodies formed during DKA and it may be present at considerable concentrations,
      contributing to the serum osmolality.

PMID- 27717594
TI  - Advances in Functional Electrical Stimulation modelling and control.

PMID- 27717593
TI  - Improved Rubin-Bodner model for the prediction of soft tissue deformations.
AB  - In craniomaxillofacial (CMF) surgery, a reliable way of simulating the soft
      tissue deformation resulted from skeletal reconstruction is vitally important for
      preventing the risks of facial distortion postoperatively. However, it is
      difficult to simulate the soft tissue behaviors affected by different types of
      CMF surgery. This study presents an integrated bio-mechanical and statistical
      learning model to improve accuracy and reliability of predictions on soft facial
      tissue behavior. The Rubin-Bodner (RB) model is initially used to describe the
      biomechanical behavior of the soft facial tissue. Subsequently, a finite element
      model (FEM) computers the stress of each node in soft facial tissue mesh data
      resulted from bone displacement. Next, the Generalized Regression Neural Network
      (GRNN) method is implemented to obtain the relationship between the facial soft
      tissue deformation and the stress distribution corresponding to different CMF
      surgical types and to improve evaluation of elastic parameters included in the RB
      model. Therefore, the soft facial tissue deformation can be predicted by
      biomechanical properties and statistical model. Leave-one-out cross-validation is
      used on eleven patients. As a result, the average prediction error of our model
      (0.7035mm) is lower than those resulting from other approaches. It also
      demonstrates that the more accurate bio-mechanical information the model has, the
      better prediction performance it could achieve.

PMID- 27717595
TI  - Probabilistic finite element method for large tumor radiofrequency ablation
      simulation and planning.
AB  - A challenging problem of radiofrequency ablation (RFA) in liver surgery is to
      accurately estimate the shapes and sizes of RFA lesions whose formation depends
      on intrinsic variations of the thermal-electrical properties of soft tissue.
      Large tumors, which can be as long as 10 cm or more, further complicate the
      problem. In this paper, a probabilistic bio-heating finite element (FE) model is
      proposed and developed to predict RFA lesions. Uncertainties of RFA lesions are
      caused by the probabilistic nature of five thermal-electrical liver properties:
      thermal conductivity, liver tissue density, specific heat, blood perfusion rate
      and electrical conductivity. Confidence levels of shapes and sizes of lesions are
      generated by the FE model incorporated with the mean-value first-order second
      moment (MVFOSM) method. Based on the probabilistic FE method, a workflow of RFA
      planning is introduced to enable clinicians to preoperatively view the predicted
      RFA lesions in three-dimension (3D) within a hepatic environment. Accurate
      planning of the RFA needle placements can then be achieved based on the
      interactive simulation and confidence level selection.

PMID- 27717596
TI  - Inositol as putative integrative treatment for PCOS.
AB  - Studies over the last decade have demonstrated that some polycystic ovary
      syndrome (PCOS) patients have abnormal insulin sensitivity (insulin resistance),
      independently from being overweight or obese. This induces the risk of developing
      type 2 diabetes in such PCOS patients. The use of insulin sensitizers (i.e.
      metformin), reduces such metabolic, and most hormonal, impairments. As metformin
      often induces side effects, new integrative strategies have been proposed to
      treat insulin resistance, such as the use of inositols. Such compounds are mainly
      represented in humans by two inositol stereoisomers: myo-inositol (MYO) and d
      chiro-inositol (DCI). MYO is the precursor of inositol triphosphate, a second
      messenger that regulates thyroid-stimulating hormone (TSH) and FSH as well as
      insulin. DCI derives from the conversion of myo-inositol via an insulin-dependent
      pathway. Several preliminary studies have indicated possible benefits of inositol
      therapy in PCOS patients, but to date no meta-analysis has been performed. This
      review aims to give clinical insights for the clinical use of inositol in PCOS.

PMID- 27717597
TI  - The Global Synanthrome Project: A Call for an Exhaustive Study of Human
      Associates.
AB  - Here we coin the term synanthrome to describe all of the species we interact
      with. We propose that the time is now here for The Global Synanthrome Project to
      describe all of our interacting species and how they have changed through time
      and across space. This effort must involve natural history, ecology, and
      evolutionary biology in addition to genomics studies that are already underway.

PMID- 27717599
TI  - Peptidic Biomaterials: From Self-Assembling to Regenerative Medicine.
AB  - Peptidic biomaterials represent a particularly exciting topic in regenerative
      medicine. Peptidic scaffolds can be specifically designed for biomimetic
      customization for targeted therapy. The field is at a pivotal point where
      preclinical research is being translated into clinics, so it is crucial to
      understand the theory and describe the status of this rapidly developing
      technology. In this review, we highlight major advantages and current limitations
      of self-assembling peptide-based biomaterials, and we discuss the most widely
      used classes of assembling peptides, describing recent and promising approaches
      in tissue engineering, drug delivery, and clinics. We also suggest design
      strategies and hurdles that still need to be overcome to fully exploit their
      therapeutic potential.

PMID- 27717598
TI  - [Statin associated myopathy in clinical practice. Results of DAMA study].
AB  - BACKGROUND AND OBJECTIVE: Muscle symptoms, with or without elevation of creatin
      kinase are one of the main adverse effects of statin therapy, a fact that
      sometimes limits their use. The aim of this study was to evaluate the clinical
      characteristics of patients treated with statins who have complained muscle
      symptoms and to identify possible predictive factors. PATIENTS AND METHODS: A
      cross-sectional one-visit, non-interventional, national multicenter study
      including patients of both sexes over 18 years of age referred for past or
      present muscle symptoms associated with statin therapy was conducted. 3,845
      patients were recruited from a one-day record from 2,001 physicians. RESULTS:
      Myalgia was present in 78.2% of patients included in the study, myositis in
      19.3%, and rhabdomyolysis in 2.5%. Patients reported muscle pain in 77.5% of
      statin-treated individuals, general weakness 42.7%, and cramps 28.1%. Kidney
      failure, intense physical exercise, alcohol consumption (>30g/d in men and 20g/d
      in women) and abdominal obesity were the clinical situations associated with
      statin myopathy. CONCLUSIONS: Myalgia followed by myositis are the most frequent
      statin-related side effects. It should be recommended control environmental
      factors such as intense exercise and alcohol intake as well as abdominal obesity
      and renal function of the patient treated with statins.

PMID- 27717600
TI  - Opportunities and challenges when pooling milk samples using ELISA.
AB  - Testing large quantities of samples in order to detect one or more test-positive
      sample(s) is expensive and time-consuming. It is possible to optimize this
      process by pooling samples. Two frameworks to produce different hierarchical and
      non-hierarchical pooling schemes were tested and compared to standard pooling.
      Their efficiency and the potential savings were determined as a function of
      prevalence and the number of pooled samples. The potential benefit of pooling
      samples is dependent upon the changes in the analytical sensitivity and
      specificity of the test used when diluting test-positive samples by pooling. To
      illustrate this, the sensitivity of antibody ELISA on pooled samples of bovine
      milk for Salmonella Dublin, Mycobacterium avium spp. paratuberculosis, and bovine
      virus diarrhea was tested. For these milk assays, the analytical sensitivity
      decreased rapidly with increasing pool sizes. The efficiency of pooling is
      usually only measured by the number of tests performed, yet real savings depend
      on all the costs involved in the pooling process. These may differ between
      laboratories depending on the available equipment and the salaries of the
      technicians, among other factors. Therefore, several cost parameters were
      introduced to describe the total cost and thereby calculate the total savings. In
      terms of overall savings, both tested schemes were potentially optimal depending
      on the prevalence, possible pool size, and the cost of retesting. For the pool
      sizes of interest in this study, the three-stage hierarchical pooling scheme was
      often marginally more efficient in terms of the total number of tests. However,
      if the price of re-pooling was high, the two-stage scheme performed better in
      terms of total savings. In addition, for low prevalences and the possibility of
      pooling a large number of samples, the two-stage non-hierarchical test may be
      more efficient, both in terms of number of tests and overall cost. In order to
      apply these results in different laboratory settings, a free Shiny WebApp was
      developed, to compare several pooling schemes with different cost parameters.

PMID- 27717602
TI  - Deep rTMS for Neuropsychiatric Symptoms of Huntington's Disease: Case Report.

PMID- 27717603
TI  - Burden, spectrum, and impact of healthcare-associated infection at a South
      African children's hospital.
AB  - BACKGROUND: In most African countries the prevalence and effects of paediatric
      healthcare-associated infection (HCAI) and human immunodeficiency virus (HIV)
      infection are unknown. AIM: To investigate the burden, spectrum, risk factors,
      and impact of paediatric HCAI by prospective clinical surveillance at a South
      African referral hospital. METHODS: Continuous prospective clinical and
      laboratory HCAI surveillance using Centers for Disease Control and Prevention
      (CDC)/National Healthcare Safety Network (NHSN) definitions was conducted at
      Tygerberg Children's Hospital, South Africa, from May 1st to October 31st in 2014
      and 2015. Risk factors for HCAI and associated mortality were analysed with
      multivariate logistic regression; excess length of stay was estimated using a
      confounder and time-matching approach. FINDINGS: HCAI incidence density was 31.1
      per 1000 patient-days (95% CI: 28.2-34.2); hospital-acquired pneumonia (185/417;
      44%), urinary tract infection (UTI) (45/417; 11%), bloodstream infection (BSI)
      (41/417; 10%), and surgical site infection (21/417; 5%) predominated. Device
      associated HCAI incidence in the paediatric intensive care unit (PICU) was high:
      15.9, 12.9 and 16 per 1000 device-days for ventilator-associated pneumonia,
      central line-associated BSI and catheter-associated UTI, respectively. HCAI was
      significantly associated with PICU stay (odds ratio: 2.0), malnutrition (1.6),
      HIV infection (1.7), HIV exposure (1.6), McCabe score 'fatal' (2.0),
      comorbidities (1.6), indwelling devices (1.9), blood transfusion (2.5), and
      transfer in (1.4). Two-thirds of paediatric deaths were HCAI-associated,
      occurring at a median of four days from HCAI onset with significantly higher
      crude mortality for HCAI-affected vs HCAI-unaffected hospitalizations [24/325
      (7.4%) vs 12/1022 (1.2%); P<0.001]. HCAI resulted in US$371,887 direct costs with
      an additional 2275 hospitalization days, 2365 antimicrobial days, and 3575
      laboratory investigations. CONCLUSION: HCAI was frequent with significant
      morbidity, mortality, and healthcare costs. Establishment of HCAI surveillance
      and prevention programmes for African children is a public health priority.

PMID- 27717601
TI  - Direct Current Stimulation Alters Neuronal Input/Output Function.
AB  - BACKGROUND: Direct current stimulation (DCS) affects both neuronal firing rate
      and synaptic efficacy. The neuronal input/output (I/O) function determines the
      likelihood that a neuron elicits an action potential in response to synaptic
      input of a given strength. Changes of the neuronal I/O function by DCS may
      underlie previous observations in animal models and human testing, yet have not
      been directly assessed. OBJECTIVE: Test if the neuronal input/output function is
      affected by DCS METHODS: Using rat hippocampal brain slices and computational
      modeling, we provide evidence for how DCS modulates the neuronal I/O function.
      RESULTS: We show for the first time that DCS modulates the likelihood of neuronal
      firing for a given and fixed synaptic input. Opposing polarization of soma and
      dendrite may have a synergistic effect for anodal stimulation, increasing the
      driving force of synaptic activity while simultaneously increasing spiking
      probability at the soma. For cathodal stimulation, however, the opposing effects
      tend to cancel. This results in an asymmetry in the strength of the effects of
      stimulation for opposite polarities. CONCLUSIONS: Our results may explain the
      asymmetries observed in acute and long term effects of transcranial direct
      current stimulation.

PMID- 27717605
TI  - Intraoral radiographic sensors: a possible source of bacterial transmission in
      the dental office.

PMID- 27717604
TI  - Healthcare-associated Gram-negative bloodstream infections: antibiotic resistance
      and predictors of mortality.
AB  - This article describes the prevalence of antibiotic resistance and predictors of
      mortality for healthcare-associated (HA) Gram-negative bloodstream infections (GN
      BSI). In total, 831 cases of HA GN-BSI from 17 intensive care units in different
      centres in Turkey were included; the all-cause mortality rate was 44%. Carbapenem
      resistance in Klebsiella pneumoniae was 38%, and the colistin resistance rate was
      6%. Multi-variate analysis showed that age >70 years [odds ratio (OR) 2, 95%
      confidence interval (CI) 1.22-3.51], central venous catheter use (OR 2.1, 95% CI
      1.09-4.07), ventilator-associated pneumonia (OR 1.9, 95% CI 1.1-3.16), carbapenem
      resistance (OR 1.8, 95% CI 1.11-2.95) and APACHE II score (OR 1.1, 95% CI 1.07
      1.13) were significantly associated with mortality.

PMID- 27717606
TI  - Department of Error.

PMID- 27717607
TI  - Early childhood development: the foundation of sustainable development.

PMID- 27717608
TI  - Good early development-the right of every child.

PMID- 27717609
TI  - Expanding the evidence base to drive more productive early childhood investment.

PMID- 27717611
TI  - A good start in life will ensure a sustainable future for all.

PMID- 27717612
TI  - The early years: silent emergency or unique opportunity?

PMID- 27717610
TI  - Investing in the foundation of sustainable development: pathways to scale up for
      early childhood development.
AB  - Building on long-term benefits of early intervention (Paper 2 of this Series) and
      increasing commitment to early childhood development (Paper 1 of this Series),
      scaled up support for the youngest children is essential to improving health,
      human capital, and wellbeing across the life course. In this third paper, new
      analyses show that the burden of poor development is higher than estimated,
      taking into account additional risk factors. National programmes are needed.
      Greater political prioritisation is core to scale-up, as are policies that afford
      families time and financial resources to provide nurturing care for young
      children. Effective and feasible programmes to support early child development
      are now available. All sectors, particularly education, and social and child
      protection, must play a role to meet the holistic needs of young children.
      However, health provides a critical starting point for scaling up, given its
      reach to pregnant women, families, and young children. Starting at conception,
      interventions to promote nurturing care can feasibly build on existing health and
      nutrition services at limited additional cost. Failure to scale up has severe
      personal and social consequences. Children at elevated risk for compromised
      development due to stunting and poverty are likely to forgo about a quarter of
      average adult income per year, and the cost of inaction to gross domestic product
      can be double what some countries currently spend on health. Services and
      interventions to support early childhood development are essential to realising
      the vision of the Sustainable Development Goals.

PMID- 27717613
TI  - Generation of global political priority for early childhood development: the
      challenges of framing and governance.
AB  - Despite progress, early childhood development (ECD) remains a neglected issue,
      particularly in resource-poor countries. We analyse the challenges and
      opportunities that ECD proponents face in advancing global priority for the
      issue. We triangulated among several data sources, including 19 semi-structured
      interviews with individuals involved in global ECD leadership, practice, and
      advocacy, as well as peer-reviewed research, organisation reports, and grey
      literature. We undertook a thematic analysis of the collected data, drawing on
      social science scholarship on collective action and a policy framework that
      elucidates why some global initiatives are more successful in generating
      political priority than others. The analysis indicates that the ECD community
      faces two primary challenges in advancing global political priority. The first
      pertains to framing: generation of internal consensus on the definition of the
      problem and solutions, agreement that could facilitate the discovery of a public
      positioning of the issue that could generate political support. The second
      concerns governance: building of effective institutions to achieve collective
      goals. However, there are multiple opportunities to advance political priority
      for ECD, including an increasingly favourable political environment, advances in
      ECD metrics, and the existence of compelling arguments for investment in ECD. To
      advance global priority for ECD, proponents will need to surmount the framing and
      governance challenges and leverage these opportunities.

PMID- 27717616
TI  - The IDEA model: A single equation approach to the Ebola forecasting challenge.
AB  - Mathematical modeling is increasingly accepted as a tool that can inform disease
      control policy in the face of emerging infectious diseases, such as the 2014-2015
      West African Ebola epidemic, but little is known about the relative performance
      of alternate forecasting approaches. The RAPIDD Ebola Forecasting Challenge
      (REFC) tested the ability of eight mathematical models to generate useful
      forecasts in the face of simulated Ebola outbreaks. We used a simple,
      phenomenological single-equation model (the "IDEA" model), which relies only on
      case counts, in the REFC. Model fits were performed using a maximum likelihood
      approach. We found that the model performed reasonably well relative to other
      more complex approaches, with performance metrics ranked on average 4th or 5th
      among participating models. IDEA appeared better suited to long- than short-term
      forecasts, and could be fit using nothing but reported case counts. Several
      limitations were identified, including difficulty in identifying epidemic peak
      (even retrospectively), unrealistically precise confidence intervals, and
      difficulty interpolating daily case counts when using a model scaled to epidemic
      generation time. More realistic confidence intervals were generated when case
      counts were assumed to follow a negative binomial, rather than Poisson,
      distribution. Nonetheless, IDEA represents a simple phenomenological model,
      easily implemented in widely available software packages that could be used by
      frontline public health personnel to generate forecasts with accuracy that
      approximates that which is achieved using more complex methodologies.

PMID- 27717615
TI  - Nurturing care: promoting early childhood development.
AB  - The UN Sustainable Development Goals provide a historic opportunity to implement
      interventions, at scale, to promote early childhood development. Although the
      evidence base for the importance of early childhood development has grown, the
      research is distributed across sectors, populations, and settings, with diversity
      noted in both scope and focus. We provide a comprehensive updated analysis of
      early childhood development interventions across the five sectors of health,
      nutrition, education, child protection, and social protection. Our review
      concludes that to make interventions successful, smart, and sustainable, they
      need to be implemented as multi-sectoral intervention packages anchored in
      nurturing care. The recommendations emphasise that intervention packages should
      be applied at developmentally appropriate times during the life course, target
      multiple risks, and build on existing delivery platforms for feasibility of scale
      up. While interventions will continue to improve with the growth of developmental
      science, the evidence now strongly suggests that parents, caregivers, and
      families need to be supported in providing nurturing care and protection in order
      for young children to achieve their developmental potential.

PMID- 27717617
TI  - What is the normal estrous cycle length for the modern dairy cow?

PMID- 27717614
TI  - Early childhood development coming of age: science through the life course.
AB  - Early childhood development programmes vary in coordination and quality, with
      inadequate and inequitable access, especially for children younger than 3 years.
      New estimates, based on proxy measures of stunting and poverty, indicate that 250
      million children (43%) younger than 5 years in low-income and middle-income
      countries are at risk of not reaching their developmental potential. There is
      therefore an urgent need to increase multisectoral coverage of quality
      programming that incorporates health, nutrition, security and safety, responsive
      caregiving, and early learning. Equitable early childhood policies and programmes
      are crucial for meeting Sustainable Development Goals, and for children to
      develop the intellectual skills, creativity, and wellbeing required to become
      healthy and productive adults. In this paper, the first in a three part Series on
      early childhood development, we examine recent scientific progress and global
      commitments to early childhood development. Research, programmes, and policies
      have advanced substantially since 2000, with new neuroscientific evidence linking
      early adversity and nurturing care with brain development and function throughout
      the life course.

PMID- 27717618
TI  - miR-21 promotes collagen production in keloid via Smad7.
AB  - OBJECTIVE: To explore the biological function of miR-21 in the formation of
      keloid. METHODS: Normal skin and keloid tissue samples underwent histopathologic
      study and qPCR analysis. The expression of miR-21 and mRNA expression of Smad7,
      Col1A1, Col3A1 in fibroblasts derived from keloid tissue and normal skin tissue
      samples were detected by qPCR. Normal and keloid fibroblasts were transfected
      with miR-21 mimics or inhibitor respectively, and expression of Smad7, Col1A1 and
      Col3A1 were examined. After the normal fibroblasts were transfected with Smad7
      siRNA, expression of Col1A1 and Col3A1 were detected by Western blot and qPCR
      analysis. RESULTS: Collagen was obviously thick and disorganized in keloid
      tissue. The expression of miR-21, Col1A1 and Col3A1 in keloid tissue and keloid
      derived fibroblasts were higher than that of normal counterparts, while the
      expression of Smad7 in keloid tissue and keloid-derived fibroblasts was lower.
      miR-21 mimics attenuated expression of Smad7, and enhanced the expression of
      Col1A1, Col3A1. Furthermore, the Smad7 siRNA increased expression of Col1A1and
      Col3A1. CONCLUSIONS: miR-21 promoted collagen production in keloid by negatively
      regulating the expression of the Smad7.

PMID- 27717620
TI  - Cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis:
      Retrospective analysis of a cohort treated in a specialized referral center.
AB  - BACKGROUND: Treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal
      necrolysis (TEN) remains controversial. OBJECTIVE: We sought to evaluate the
      impact of cyclosporine on hospital mortality in patients with SJS/TEN. METHODS:
      All patients with SJS and TEN admitted to our center from 2011 to 2014 were
      treated under a standardized protocol that allowed for cyclosporine therapy if
      the inclusion and exclusion criteria were met. Clinical data were reviewed
      retrospectively. Comparative analysis was made on mortality outcomes with
      patients treated with cyclosporine versus what was expected based on SCORTEN.
      RESULTS: In all, 44 patients were admitted during the study period. A total of 24
      patients received cyclosporine and the remaining 20 patients were treated
      supportively. SCORTEN predicted 7.2 deaths and 3 were observed in the group
      treated with cyclosporine. In the group treated supportively, SCORTEN predicted
      5.9 deaths and 6 deaths were observed. The standardized mortality ratio of
      SJS/TEN treated with cyclosporine was 0.42 (95% confidence interval 0.09-1.22).
      LIMITATION: Small sample size, retrospective design, and referral bias are
      limitations. CONCLUSION: The use of cyclosporine may improve mortality in SJS/TEN
      and needs to be validated in controlled studies.

PMID- 27717619
TI  - Diffuse atrophic papules and plaques, intermittent abdominal pain, paresthesias,
      and cardiac abnormalities in a 55-year-old woman.
AB  - KEY TEACHING POINTS.

PMID- 27717621
TI  - Melanoma-associated leukoderma and vitiligo cannot be differentiated based on
      blinded assessment by experts in the field.
AB  - BACKGROUND: Melanoma-associated leukoderma (MAL) is a depigmenting disorder that
      can occur spontaneously in patients with melanoma. The differences in clinical
      presentation between MAL and vitiligo are not well defined. This may lead to
      misdiagnosing MAL as vitiligo, resulting in delayed detection of melanoma.
      OBJECTIVE: The objective of this study was to assess whether experts in the field
      can distinguish between MAL and vitiligo, and to assess if discriminative
      features can be identified. METHODS: We designed an image comparison study in
      which 4 experts in the field blindly assessed photographs followed by medical
      history of 11 patients with MAL and 33 with vitiligo. RESULTS: The assessors
      misdiagnosed 72.7% of MAL cases and marked 80.0% of them as typical vitiligo. The
      median age at onset of the leukoderma was higher (55 years, P = .001) in MAL. No
      discriminative features were found. LIMITATIONS: Sampling bias because of
      inclusion in tertiary referral center is a limitation. CONCLUSION: The clinical
      presentation of leukoderma in patients with melanoma resembles that of vitiligo.
      We propose "melanoma-associated vitiligo" as the more appropriate term for
      leukoderma in patients with melanoma. Clinicians should be aware that
      depigmentation in vitiligo can also be caused by melanoma-associated vitiligo and
      a total body inspection should be performed.

PMID- 27717622
TI  - WHO strategies for the management of drug-resistant tuberculosis.

PMID- 27717623
TI  - Association between the Family Nutrition and Physical Activity Screening Tool and
      obesity severity in youth referred to weight management.
AB  - BACKGROUND: The Family Nutrition and Physical Activity Screening Tool (FNPA)
      evaluates family behavioural and environmental factors associated with pediatric
      obesity, but it is unknown if FNPA scores differ among youth across obesity
      severities. Our aim was to determine the association between the FNPA and obesity
      severity in youth referred to weight management. METHODS: Upon initiating
      treatment, height, weight, and the FNPA were collected according to standard
      procedures. Cut-points for overweight/obesity, severe obesity (SO) class 2, and
      SO class 3 were calculated. FNPA scores were compared across weight status groups
      using analysis of covariance, and odds of SO across FNPA quartiles were evaluated
      with multiple logistic regression. RESULTS: Participants included 564 5-18year
      old who initiated treatment and completed the FNPA. After adjustment, FNPA scores
      differed by weight status with higher/healthier scores in youth with
      overweight/obesity (56.6+/-8.5) when compared to those with SO class 2 (55.0+/
      7.1; p=0.015) or SO class 3 (53.6+/-9.0; p<0.001). Compared to those in the
      highest FNPA quartile, youth in the 2nd quartile had 1.8 (95% CI: 1.1, 2.9) times
      higher odds of SO, and those in the lowest FNPA quartile had 2.1 (95% CI: 1.3,
      3.4) times higher odds of SO. Youth with SO had unhealthier subscale scores among
      6 of 10 constructs, including nutritional, physical activity, sedentary, and
      sleep behaviours. CONCLUSIONS: Results suggest a consistent inverse relationship
      between the FNPA and adiposity among youth presenting for weight management. The
      FNPA is a useful metric for programs and clinicians targeting family behaviours
      and the home environment to combat obesity.

PMID- 27717624
TI  - Differences in Pediatric Non-Interventional Radiology Procedural Sedation
      Practices and Adverse Events by Registered Nurses and Physicians.
AB  - PURPOSE: The purpose of this study was to determine differences in sedation
      related adverse events according to the type of provider monitoring and
      delivering sedation. DESIGN AND METHODS: A retrospective, cross-sectional,
      correlational design using secondary data from the Pediatric Sedation Research
      Consortium database was used for this study. RESULTS: A sample of 36,352 cases (0
      14 years of age) sedated and monitored for diagnostic radiology procedures by
      three types of providers (registered nurses [RNs] alone, physicians (MDs) alone,
      or registered nurse + physician [RN+MD sedation teams]) were compared. Patients
      sedated by RNs alone or MDs alone had lower odds of unanticipated adverse events
      (odds ratios 0.46 and 0.53, respectively; p<0.0001) compared with RN+MD sedation
      provider teams. CONCLUSIONS: Team skills may be an important competency for RN+MD
      sedation teams in the non-interventional radiology setting. PRACTICE
      IMPLICATIONS: This study can inform clinicians, administrators, and quality
      improvement managers of the differences in adverse event outcomes of pediatric
      radiology procedures when RN+MD teams provide sedation compared with RNs or MDs
      alone.

PMID- 27717625
TI  - Lumbar synovial cysts: presentation of a series of 10 cases and literature
      review.
AB  - INTRODUCTION: Although they are freqqently described in the literature, lumbar
      synovial cysts are a relative uncommon cause of low back and radicular leg pain.
      OBJECTIVE: To evaluate the treatment and surgical outcomes of the lumbar synovial
      cysts operated on in our hospital during a 5 year period. MATERIAL AND METHODS: A
      retrospective study was conducted on patients surgically treated in our
      department from August 2009 to September 2014, using a visual analogue scale for
      the clinical follow-up in the first year after surgery. RESULTS: After the
      surgical treatment (surgical removal of the synovial cyst with or without
      instrumented arthrodesis with transpedicular screws) of 10 patients (5 female and
      5 male) with a mean age of 70.2 years (range 50-80), the clinical outcome was
      satisfactory in 80% of the patients, with the resolving of their symptoms.
      CONCLUSIONS: Lumbar synovial cysts have to be considered in the differential
      diagnosis in patients with low back and radicular leg pain. The majority of the
      patients are in their sixties and have lumbar degenerative spondylopathy.
      Nowadays, surgical resection of the lumbar synovial cysts and spinal fusion are
      the recommended treatment, because it is thought that the increased movement of
      the spine is one to the causes of the cyst formation. More studies are still
      needed, hence the relevance of this article.

PMID- 27717626
TI  - Functional outcome after transphyseal anterior cruciate ligament reconstruction
      in young patients with open growth plates.
AB  - BACKGROUND: This study evaluates sports ability, rotational laxity and potential
      growth changes in children after transphyseal ACL reconstruction with metaphyseal
      fixation technique, considering physis biology by placing drill holes vertically
      in the femoral anatomic origin in order to reduce volumetric injury to the
      physis. METHODS: In this retrospective trial of 42 patients data were collected.
      Thirty-seven were reviewed measuring rotational laxity and anteroposterior tibial
      translation using the Laxitester (ORTEMA Sport Protection, Markgroeningen,
      Germany) and the KT1000. Clinical examination was evaluated with the IKDC 2000
      knee examination form. Leg axis was determined with digital photography and leg
      length was assessed clinically. Sports ability was assessed with questionnaires
      including subjective IKDC, Tegner Activity Scale, Activity Rating Scale and a
      questionnaire on sports and level of sports. RESULTS: Mean follow-up was
      24.9months. Mean age at surgery was 13.2years in boys and 13.1years in girls.
      IKDC 2000 grading was A or B in 28 patients and C in nine patients. Significant
      increased anterior tibial translation was observed in neutral position and in
      external tibia rotation. No growth abnormalities were seen. Fifty-seven percent
      of the patients were able to participate in competitive sports at follow-up.
      CONCLUSION: Transphyseal ACL reconstruction with metaphyseal fixation in children
      with open growth plates can be done with low risk of growth changes. Return to
      competitive sports is possible although low rotational laxity still exists. LEVEL
      OF EVIDENCE: IV.

PMID- 27717627
TI  - Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation.
AB  - Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has
      raised global concern due to its association with a significant rise in the
      number of infants born with microcephaly and neurological disorders such as
      Guillain-Barre syndrome. We developed prototype subunit and adenoviral-based Zika
      vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused
      to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was
      delivered intradermally through carboxymethyl cellulose microneedle array (MNA).
      The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was
      tested in C57BL/6 mice. Prime/boost immunization regimen was associated with
      induction of a ZIKV-specific antibody response, which provided neutralizing
      immunity. Moreover, protection was evaluated in seven-day-old pups after virulent
      ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl
      were all protected against lethal challenge infection without weight loss or
      neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were
      partially protected (50%). No protection was seen in pups born to phosphate
      buffered saline-immunized mice. This study illustrates the preliminary efficacy
      of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a
      promising candidate vaccine and antigen format for the prevention of Zika virus
      disease.

PMID- 27717628
TI  - Intestinal obstruction in adults due to ileal intussusception secondary to
      inflammatory fibroid polyp: A case report.

PMID- 27717629
TI  - Clinical impact of serum albumin on nonvariceal upper gastrointestinal bleeding.

PMID- 27717630
TI  - A novel technique for correction of total rectal prolapse: Endoscopic-assisted
      percutaneous rectopexy with the aid of the EndoLifter.
AB  - INTRODUCTION AND AIMS: Rectal prolapse is common in the elderly, having an
      incidence of 1% in patients over 65years of age. The aim of this study was to
      evaluate the safety and feasibility of a new endoluminal procedure for attaching
      the previously mobilized rectum to the anterior abdominal wall using an
      endoscopic fixation device. MATERIALS AND METHODS: The study is a single-arm
      phasei experimental trial. Under general anesthesia, total rectal prolapse was
      surgically reproduced in five pigs. Transanal endoscopic reduction of the rectal
      prolapse was performed. The best site for transillumination of the abdominal
      wall, suitable for rectopexy, was identified. The EndoLifter was used to
      approximate the anterior wall of the proximal rectum to the anterior abdominal
      wall. Two percutaneous rectopexies were performed by puncture with the Loop
      FixtureII Gastropexy Kit(r) at the preset site of transillumination. After the
      percutaneous rectopexies, rectoscopy and exploratory laparotomy were performed.
      Finally, the animals were euthanized. RESULTS: The mean procedure time was 16min
      (11-21) and the mean length of the mobilized specimen was 4.32cm (range 2.9
      5.65cm). A total of 10 fixations were performed with a technical success rate of
      100%. There was no evidence of postoperative rectal prolapse in any of the
      animals. The EndoLifter facilitated the process by allowing the mucosa to be held
      and manipulated during the repair. CONCLUSIONS: Endoscopic-assisted percutaneous
      rectopexy is a safe and feasible endoluminal procedure for fixation of the rectum
      to the anterior abdominal wall in experimental animals.

PMID- 27717631
TI  - Global research priorities to accelerate early child development in the
      sustainable development era.

PMID- 27717632
TI  - Risk of poor development in young children in low-income and middle-income
      countries: an estimation and analysis at the global, regional, and country level.
AB  - BACKGROUND: A 2007 study published in The Lancet estimated that approximately 219
      million children aged younger than 5 years were exposed to stunting or extreme
      poverty in 2004. We updated the 2004 estimates with the use of improved data and
      methods and generated estimates for 2010. METHODS: We used country-level
      prevalence of stunting in children younger than 5 years based on the 2006 Growth
      Standards proposed by WHO and poverty ratios from the World Bank to estimate
      children who were either stunted or lived in extreme poverty for 141 low-income
      and middle-income countries in 2004 and 2010. To avoid counting the same children
      twice, we excluded children jointly exposed to stunting and extreme poverty from
      children living in extreme poverty. To examine the robustness of estimates, we
      also used moderate poverty measures. FINDINGS: The 2007 study underestimated
      children at risk of poor development. The estimated number of children exposed to
      the two risk factors in low-income and middle-income countries decreased from
      279.1 million (95% CI 250.4 million-307.4 million) in 2004 to 249.4 million
      (209.3 million-292.6 million) in 2010; prevalence of children at risk fell from
      51% (95% CI 46-56) to 43% (36-51). The decline occurred in all income groups and
      regions with south Asia experiencing the largest drop. Sub-Saharan Africa had the
      highest prevalence in both years. These findings were robust to variations in
      poverty measures. INTERPRETATION: Progress has been made in reducing the number
      of children exposed to stunting or poverty between 2004 and 2010, but this is
      still not enough. Scaling up of effective interventions targeting the most
      vulnerable children is urgently needed. FUNDING: National Institutes of Health,
      Bill & Melinda Gates Foundation, Hilton Foundation, and WHO.

PMID- 27717633
TI  - Failure of communication: a patient's story.
AB  - The first author, a patient who underwent elective caesarean section and felt
      pain necessitating conversion to general anaesthesia, describes the experience
      with particular reference to the perceived poor communication between her and her
      anaesthetist. This extended from the preoperative visit to the information
      provided to her general practitioner after discharge. She makes several
      suggestions which would have made her experience, and those of other patients in
      similar circumstances, less traumatic. The second author, who had no involvement
      in events and works in a different Trust, comments upon the events from the
      perspective of an obstetric anaesthetist.

PMID- 27717634
TI  - Clinical effectiveness of transversus abdominis plane (TAP) blocks for pain
      relief after caesarean section: a meta-analysis.
AB  - BACKGROUND: The effectiveness of transversus abdominis plane (TAP) blocks for
      acute pain relief after caesarean section, in comparison to normal practice,
      remains uncertain. METHODS: Electronic literature databases were searched from
      inception to May 2016 for randomised controlled trials that assessed the
      effectiveness of TAP blocks following caesarean section. Trials were eligible if
      comparisons were made against no block or placebo, and/or intrathecal morphine.
      Risk of bias was assessed using the Cochrane tool. Data for consistent outcomes
      were subject, where possible, to meta-analysis and presented as either mean
      differences with 95% confidence intervals or incidence of a particular event.
      RESULTS: Twenty published studies fulfilled our inclusion criteria. TAP blocks
      significantly reduced pain at rest both when compared with placebo or no TAP
      blocks (-0.96, 95% CI -1.67 to -0.25, P=0.008) and intrathecal morphine (1.10,
      95% CI 0.59 to 1.60, P<0.0001). Both these comparisons showed the greatest
      improvement with pain on movement, (-1.58, 95% CI -2.69 to -0.47, P=0.005 and
      1.35, 95% CI 0.76 to 1.94, respectively, P<0.00001). Morphine consumption was
      significantly reduced with TAP blocks when compared to placebo or no TAP blocks (
      15.88, 95% CI -22.02 to -9.73, P<0.00001). This significance was lost when TAP
      blocks were both compared to intrathecal morphine (0.89, 95% CI -0.64 to 2.43,
      P=0.25) and given in co-administration (0.00, 95% CI -0.10 to 0.10, P=1.00).
      CONCLUSION: TAP blocks provide effective analgesia after caesarean section;
      however, additional benefits are more difficult to demonstrate when long-acting
      intrathecal opioids are administered.

PMID- 27717635
TI  - Dose-response of intrathecal morphine when administered with intravenous
      ketorolac for post-cesarean analgesia: a two-center, prospective, randomized,
      blinded trial.
AB  - BACKGROUND: The appropriate dose of intrathecal morphine for post-cesarean
      analgesia is unclear. With the inclusion of routine non-steroidal anti
      inflammatory drugs, the required dose of morphine may be significantly less than
      the 200-300MUg common a decade ago. We performed a two-center, prospective,
      randomized, blinded trial comparing three doses of intrathecal morphine, combined
      with routine intravenous ketorolac, in 144 healthy women undergoing elective
      cesarean delivery. METHODS: Patients received an intrathecal injection of
      hyperbaric bupivacaine 12mg, fentanyl 15MUg and a randomized dose of 50, 100, or
      150MUg morphine in a volume of 2.2mL. Patients received intravenous ketorolac
      30mg before leaving the operating room and 15mg intravenously every 6h for the
      duration of the study (24h). All received postoperative patient-controlled
      intravenous morphine. The primary endpoint was total intravenous morphine
      administered postoperatively over 24h, analyzed using mixed model regression.
      RESULTS: There were no differences between dose groups (or institutions) in
      intravenous morphine use over 24h. Visual analog scale scores for pain and nausea
      did not differ. Pruritus was greater in the 100 and 150MUg groups than the 50MUg
      group at 6h and 12h, but there was no difference between groups in nausea or
      pruritus treatments. Respiratory depression or significant sedation did not
      occur. CONCLUSION: The dose-response relationship of intrathecal morphine for
      multimodal post-cesarean analgesia suggests that 50MUg produces analgesia similar
      to that produced by either 100MUg or 150MUg.

PMID- 27717636
TI  - The effect of dalteparin on thromboelastography in pregnancy: an in vitro study.
AB  - BACKGROUND: Dalteparin is often used for prophylaxis or treatment of venous
      thromboembolism during pregnancy, yet there is no laboratory test to accurately
      reflect its clinical activity. Thromboelastography is a point-of-care monitor of
      whole blood coagulation. The aim of this study was to determine if serial doses
      of dalteparin added in vitro to whole blood samples from term, pregnant women are
      detectable as changes in thromboelastography parameters. METHODS: Thirty healthy
      parturients presenting for elective caesarean section were recruited. Dalteparin
      was added to whole blood samples to yield final concentrations of 0 (control),
      0.05, 0.25, 0.5, 0.75 and 1.0U/mL anti-Xa activity. Thromboelastography tracings
      were obtained for all six samples using the standard kaolin protocol. RESULTS:
      Significant differences were noted in median thromboelastography r time, k time,
      alpha angle and maximal amplitude between non-anticoagulated (?0.05U/mL) and
      samples ?0.5U/mL (P<0.05). The r time and k time presented with the highest
      sensitivities of 97.5 and 84.0, respectively. CONCLUSION: This pilot study
      provides proof-of-concept that thromboelastography can discriminate differences
      in blood anticoagulated with varying doses of dalteparin in a dose-dependent
      manner. This suggests that thromboelastography may be a feasible monitor of
      anticoagulation in the presence of dalteparin in maternal whole blood and may
      potentially translate to a point-of-care test that can be used to determine real
      time coagulation status in patients.

PMID- 27717638
TI  - Photoacoustic calorimetry studies of CO photo-dissociation from chloramine-T
      modified horse heart cytochrome-c.
AB  - Treatment of horse heart Cytochrome-c (Cc) with N-chloro-4-toluosulfonamide
      (Chloramine-t, CT) results in the oxidation of methionine (Met) residues to the
      corresponding sulfoxide including the distal heme ligand, Met80. The resulting Fe
      sulfoxide coordination is sufficiently labile in the ferrous form to be displaced
      by gaseous ligands, including CO. Photolysis of the CO-CT-Cc complex provides an
      opportunity to examine ligand binding dynamics that are associated with a
      relatively rigid distal heme pocket. In this work, photoacoustic calorimetry
      (PAC) was utilized to obtain the kinetics as well as enthalpy and molar volume
      changes subsequent to CO photo-dissociation from CO-CT-Cc. Previous photolysis
      studies of CO-CT-Cc have led to a proposed model for ligand recombination in
      which the Met80-sulfoxide and CO recombine with the heme on relatively slow
      timescales (50 MUs and ~500 MUs, respectively). The PAC data presented here
      reveals two additional kinetic phases with lifetimes of <20 ns and 534 +/- 75 ns.
      The fast phase (<20 ns) is associated with an DeltaH of 44 +/- 5 kcal mol-1 and
      DeltaV of -0.5 +/- 0.5 mL mol-1, whereas the slower phase (534 ns) is associated
      with a small DeltaH of 2 +/- 3 kcal mol-1 and DeltaV of 1 +/- 0.5 mL mol-1.

PMID- 27717637
TI  - [Algorithm for surgical treatment of limb lymphedema].
AB  - Whether primary or secondary, limb lymphedema is a relatively common disease
      whose impact on the quality of life of patients is important. Although the
      microsurgical reconstruction techniques seem to be the techniques of choice in
      the treatment of limb lymphedema, no consensus about treatment of limb lymphedema
      has yet been defined. Considering the advantages and disadvantages of surgical
      techniques and their impact on the quality of life of patients, we propose a
      surgical treatment algorithm of limb lymphedema.

PMID- 27717639
TI  - The preferential heterodimerization of human small heat shock proteins HSPB1 and
      HSPB6 is dictated by the N-terminal domain.
AB  - Small heat shock proteins are ATP-independent molecular chaperones. Their
      function is to bind partially unfolded proteins under stress conditions. In vivo,
      members of this chaperone family are known to preferentially assemble together
      forming large, polydisperse heterooligomers. The exact molecular mechanisms that
      drive specific heteroassociation are currently unknown. Here we study the
      oligomers formed between human HSPB1 and HSPB6. Using small-angle X-ray
      scattering we could characterize two distinct heterooligomeric species present in
      solution. By employing native mass spectrometry we show that such assemblies are
      formed purely from heterodimeric building blocks, in line with earlier cross
      linking studies. Crucially, a detailed analysis of truncation variants reveals
      that the preferential association between these two sHSPs is solely mediated by
      their disordered N-terminal domains.

PMID- 27717641
TI  - In Reply to 'The US Renal Data System "Pie Chart of Death"'.

PMID- 27717640
TI  - Evaluation on preoperative assessment of obese patients.

PMID- 27717642
TI  - The Greenland shark: A new challenge for the oxidative stress theory of ageing?
AB  - The free radical theory of ageing predicts that long-lived species should be more
      resistant to oxidative damage than short-lived species. Although many studies
      support this theory, recent studies found notable exceptions that challenge the
      generality of this theory. In this study, we have analysed the oxidative status
      of the Greenland shark (Somniosus microcephalus), which has recently been found
      as the longest living vertebrate animal known to science with a lifespan of at
      least 272years. As compared to other species, the Greenland shark had body mass
      corrected values of muscle glutathione peroxidase and red blood cells protein
      carbonyls (metric of protein oxidative damage) above 75 percentile and below 25
      percentile, respectively. None of the biochemical metrics of oxidative status
      measured in either skeletal muscle or red blood cells were correlated with
      maximum lifespan of species. We propose that the values of metrics of oxidative
      status we measured might be linked to ecological features (e.g., adaptation to
      cold waters and deep dives) of this shark species rather to its lifespan.

PMID- 27717644
TI  - Corrigendum to 'Editorial' [International Journal of Infectious Diseases 50
      (2016) 83-84].

PMID- 27717643
TI  - Comparative Effectiveness and Safety of Preoperative Lung Localization for
      Pulmonary Nodules: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: An optimal method of preoperative localization for pulmonary nodules
      has yet to be established. This systematic review and meta-analysis aimed to
      compare the success and complication rates associated with three pulmonary nodule
      localization methods for video-assisted thoracoscopic surgery (VATS): hook-wire
      localization, microcoil localization, and lipiodol localization. METHODS: We
      searched the PubMed, MEDLINE, and EMBASE databases for prospective or
      retrospective English language studies of VATS localization in adult patients. A
      noncomparative, random effects model-based meta-analysis was performed to obtain
      pooled success and complication rates for the three localization methods.
      RESULTS: A total of 46 clinical studies were enrolled, including 30, 9, and 7
      studies of hook-wire, microcoil, and lipiodol localization, respectively. The
      successful targeting rates for hook-wire, microcoil, and lipiodol localization
      were 0.98 (95% CI, 0.97-0.99), 0.98 (95% CI, 0.96-0.99), and 0.99 (95% CI, 0.98
      1.00), respectively, with corresponding successful operative field targeting
      rates of 0.94 (95% CI, 0.91-0.96), 0.97 (95% CI, 0.95-0.98), and 0.99 (95% CI,
      0.98-1.00), respectively. In addition, the successful VATS rates with hook-wire,
      microcoil, and lipiodol localization were 0.96 (95% CI, 0.94-0.97), 0.97 (95% CI,
      0.94-0.99), and 0.99 (95% CI, 0.98-1.00), respectively. Regarding complications,
      hook-wire, microcoil, and lipiodol localization were associated with pneumothorax
      rates of 0.35 (95% CI, 0.28-0.43), 0.16 (95% CI, 0.07-0.34), and 0.31 (95% CI,
      0.20-0.46), respectively and hemorrhage rates of 0.16 (95% CI, 0.11-0.23), 0.06
      (95% CI, 0.03-0.11), and 0.12 (95% CI, 0.05-0.23), respectively. CONCLUSIONS: All
      three localization methods yielded similarly highly successful targeting rates.
      However, hook-wire localization had a relatively lower successful operative field
      targeting rate because of dislodgement or migration. Lipiodol localization had
      the highest overall success rate, and microcoil localization yielded the lowest
      complication rates.

PMID- 27717646
TI  - Assessment of vitamin D levels, awareness among Lebanese pharmacy students, and
      impact of pharmacist counseling.
AB  - Vitamin D inadequacy, frequently underdiagnosed, affects people of all age groups
      worldwide. This prospective study aims at determining the percentage of
      inadequate vitamin D levels among students and evaluating the impact of
      pharmacist counseling on raising the awareness of the importance of sun exposure
      and adequate vitamin D intake. A total of 160 university students were recruited.
      Blood samples were taken to check the vitamin D, calcium, and phosphorous levels.
      Vitamin D levels ?30ng/mL were defined as inadequate. Scores were given to the
      questions and aimed at gathering patient knowledge about vitamin D before and
      after pharmacist counseling. A total of 115 (71.87%) patients had vitamin D
      levels <30ng/mL, with a mean vitamin D serum level of 16.80+/-5.85ng/mL. The mean
      level of calcium was 9.51+/-1.23mg/dL and, of phosphorus 3.62+/-0.95mg/dL. The
      mean difference in the knowledge score of the recommended daily amount of vitamin
      D before and after pharmacist counseling was 2.81 versus 5.88 (p<0.001).
      Concerning patient education for diseases and drugs that affect vitamin D levels,
      pharmacist counseling was effective in raising the awareness (p<0.001). Given
      that vitamin D inadequacy is linked to many disease progressions, it is important
      that health professionals provide interventional strategies and education
      measures to correct inadequate levels in patients of all age groups.

PMID- 27717645
TI  - Transorganogenesis and transdifferentiation in C. elegans are dependent on
      differentiated cell identity.
AB  - The differentiated cell identities and structure of fully formed organs are
      generally stable after their development. In contrast, we report here that
      development of the C. elegans proximal somatic gonad (hermaphrodite uterus and
      spermathecae, and male vas deferens) can be redirected into intestine-like organs
      by brief expression of the ELT-7 GATA transcription factor. This process converts
      one developing organ into another and can hence be considered
      "transorganogenesis." We show that, following pulsed ELT-7 expression, cells of
      the uterus activate and maintain intestine-specific gene expression and are
      transformed at the ultrastructural level to form an epithelial tube resembling
      the normal intestine formed during embryogenesis. Ubiquitous ELT-7 expression
      activates intestinal markers in many different cell types but only cells in the
      somatic gonad and pharynx appear to become fully reprogrammed. We found that
      ectopic expression of other endoderm-promoting transcription factors, but not
      muscle- or ectoderm- promoting transcription factors, redirects the fate of these
      organs, suggesting that pharyngeal and somatic gonad cells are specifically
      competent to adopt intestine identity. Although the intestine, pharynx, and
      somatic gonad are derived from distant cell lineages, they all express the PHA
      4/FoxA transcription factor. While we found that post-embryonic PHA-4 is not
      necessary for pharynx or uterus reprogramming and PHA-4 is not sufficient in
      combination with ELT-7 to induce reprogramming in other cells types, knock down
      of PHA-4 during embryogenesis, which abolishes normal pharynx differentiation,
      prevents pharyngeal precursors from being reprogrammed into intestine. These
      results suggest that differentiated cell identity determines susceptibility to
      transdifferentiation and highlight the importance of cellular context in
      controlling competency for reprogramming.

PMID- 27717647
TI  - Bariatric Embolization: Pilot Study on the Impact of Gastroprotective Agents and
      Arterial Distribution on Ulceration Risk and Efficacy in a Porcine Model.
AB  - PURPOSE: To assess whether the number of fundal arteries embolized and use of
      gastroprotective agents have an impact on ghrelin suppression and gastric
      ulceration rates. MATERIALS AND METHODS: Twenty-two healthy, growing swine (mean,
      38.4 kg; range, 30.3-47.0 kg) were evaluated. Six control swine underwent a sham
      procedure. Gastric embolization was performed by the infusion of 40-um
      microspheres selectively into some or all gastric arteries supplying the gastric
      fundus. In group 1, 6 swine underwent embolization of all 4 arteries to the
      gastric fundus. In group 2, 5 swine underwent embolization of 2 gastric fundal
      arteries. In group 3, 5 swine underwent embolization of 1 gastric fundal artery.
      Animals in groups 2 and 3 were treated with gastroprotective agents (sucralfate
      and omeprazole). Weight and fasting plasma ghrelin levels were analyzed at
      baseline and at week 4. Upon animal euthanasia, gross analysis was performed for
      identification of ulcers. RESULTS: Only group 1 animals exhibited changes in
      serum ghrelin levels that rendered them significantly lower than those in control
      animals (P = .049). Group 3 animals exhibited marked elevations in serum ghrelin
      levels compared with control animals (P = .001). Gross pathologic evaluation
      revealed 0 ulcers in the control animals, 3 ulcers (50%) in group 1, 2 ulcers
      (40%) in group 2, and 2 ulcers (40%) in group 3. CONCLUSIONS: Administration of
      gastroprotective agents and embolization of fewer arteries to the gastric fundus
      did not prevent gastric ulceration in treated animals. Only animals that
      underwent embolization of all gastric arteries exhibited significant decreases in
      serum ghrelin levels.

PMID- 27717648
TI  - Phenotypic characteristics and comparative proteomics of Staphylococcus aureus
      strains with different vancomycin-resistance levels.
AB  - Reduced vancomycin susceptibility of methicillin-resistant Staphylococcus aureus
      (MRSA) is a worldwide problem. Unfortunately, its genetic marker and molecular
      mechanisms remained unknown. This study investigated differential phenotypic
      characteristic and protein expression profiles among three groups of MRSA
      isolates, including vancomycin-susceptible S. aureus (VSSA), heterogeneous
      vancomycin-intermediate S. aureus (hVISA) and vancomycin-intermediate S. aureus
      (VISA) (n = 7 isolates/group). Phenotypic characteristic revealed significant
      greater number of isolates with non-spreading colony in VISA as compared to both
      VSSA and hVISA groups. 2-DE followed by nanoLC-MS/MS analyses revealed increased
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in both hVISA and VISA, whereas
      50S ribosomal protein L14 (RplN) and DNA-binding protein II (Hup) were increased
      only in VISA. The non-spreading colony and GAPDH level of MRSA may be used as the
      markers for differentiation of VSSA, hVISA and VISA.

PMID- 27717649
TI  - Correlation of clinical, laboratory and drug susceptibility profiles in 176
      patients with culture positive TBM in a tertiary neurocare centre.
AB  - Drug resistance has increased the difficulties in control of tuberculosis
      infection. The present study evaluated the clinical and laboratory features among
      tuberculous meningitis (TBM) patients and the drug susceptibility of
      Mycobacterium tuberculosis (M.tb) isolated from CSF. Out of 698 CSF samples, 176
      (25.21%) were M.tb culture positive. Among the clinical signs and symptoms,
      fever, headache and altered sensorium were found to be statistically significant
      (P<0.05). ELISA was a better predictor of disease and found to be statistically
      significant (P<0.001) in culture-proven TBM cases. Totally, 57 (32.4%) isolates
      were resistant to one or more drugs that include 5 (2.8%) multidrug-resistant
      isolates. In conclusion, the search for antibody in CSF and also CSF chloride can
      represent as an adjunct in the diagnosis of TBM. Screening of drug susceptibility
      is a very important factor and would help in better management of the disease.

PMID- 27717650
TI  - The distribution and drug susceptibilities of clinical Candida species in TSARY
      2014.
AB  - The species distribution and drug susceptibilities of 1106 Candida isolates
      collected in Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) in
      2014 were determined. Candida albicans is still the dominant species, accounting
      for 35.9%, followed by 28.3% C. glabrata, 26.6% C. tropicalis, 5.2% C.
      parapsilosis, 1.0% C. krusei, and 3.0% of 13 other species. Interestingly, the
      prevalence of candidemia caused by C. glabrata in the present study is
      significantly higher than that in previous three surveys (39/220 vs. 54/471,
      P=0.025). We found that 31 (2.8%), 24 (2.2%), 1 (0.09%), and 0 isolates were
      resistant to fluconazole, voriconazole, anidulafungin, and amphotericin B,
      respectively. There is a significant increase in fluconazole (P=0.00002) and
      voriconazole (P=0.00006) resistant rates when compared to the isolates collected
      in 2010. Importantly, all the 24 voriconazole resistant isolates identified were
      also resistant to fluconazole. Hence, cross-resistance among azole-type drugs is
      an emerging issue for managing fungal infections.

PMID- 27717651
TI  - Inquilinus limosus in pulmonary disease: case report and review of the
      literature.
AB  - Inquilinus limosus is a slow growing, gram-negative, oxidase-positive, non
      fermentative bacillus that is rarely isolated from clinical samples. When
      clinically identified, I. limosus is almost exclusively isolated from the
      respiratory tracts of patients with cystic fibrosis (CF). We report the first
      case of I. limosus isolation from a pulmonary specimen in an individual without a
      diagnosis of CF. A review of the English-language literature has been made and
      shows 33 cases (excluding the present report) in which I. limosus was isolated
      from the respiratory tracts of patients. Our patient, at 60years of age, is more
      than two decades older than the any previously reported patient. Similar to
      previous reports, the I. limosus isolated from her lungs demonstrated intrinsic
      multidrug resistance. The pathogenicity, clinical relevance, and optimal
      therapeutic management of I. limosus remains largely unknown due to its
      infrequent recovery from clinical samples.

PMID- 27717652
TI  - Synthesis and evaluation of the structural elements in alkylated
      tetrahydroisoquinolines for binding to CNS receptors.
AB  - Diseases of the CNS are often complex and involve multiple receptor systems and
      thus, the treatment options for these diseases must focus on targeting the
      multiple receptors implicated in the various disorders. Schizophrenia and
      depression are examples of such diseases and their pharmacotherapy thus depends
      on agents which target multiple receptors including the dopamine, serotonin and
      even cholinergic receptors at the same time. In our previous campaign to find
      multi-receptor ligands, we have identified the benzothiazole 1a as an initial
      lead molecule. In the current work, we have expanded the structure affinity
      relationship (SAFIR) of 1a resulting in the identification of a partially
      restrained butyrophenone 3j as a potent and selective dual 5-HT1A and 5-HT7
      receptor ligand. It is expected that compound 3j may serve as a new lead for
      further development in our search for newer and novel ligands with the potential
      to treat diseases of CNS origin.

PMID- 27717653
TI  - The time dependence of the effect of ischemic preconditioning on successive
      sprint swimming performance.
AB  - OBJECTIVES: The present study aimed to determine the effects of ischemic
      preconditioning on performance in three successive 50-m swimming trials and to
      measure stroke rate, stroke length and blood lactate accumulation. DESIGN:
      Counterbalanced, repeated-measures cross-over study. METHODS: On two separate
      days, eleven competitive male swimmers (20+/-3 years, 182+/-5cm, 77+/-5kg)
      performed three successive 50-m trials in a 50-m swimming pool, preceded by
      intermittent bilateral cuff inflation (4* 5-min of blood flow restriction+5-min
      of cuff deflation) at either 220 for thighs and 180mmHg for arms (ischemic
      preconditioning) or 20mmHg for both limbs (control-treatment). The 50-m trials
      were conducted 1-, 2-, and 8-h after the procedure. RESULTS: While no ergogenic
      effect of ischemic preconditioning was observed for 1-h (0.4%, 95% confidence
      limits of +/-0.6%, p=0.215), there were clear beneficial effects of ischemic
      preconditioning on 2- and 8-h (1.0% and 1.2%, respectively; 95% confidence limits
      of +/-0.6% in both cases, p<=0.002). Furthermore, ischemic preconditioning
      increased blood lactate accumulation in 2-(p<0.001) and 8-h (p=0.010) and stroke
      rate for 2- and 8-h in specific 10-m segments (p<0.05). CONCLUSIONS: These
      findings suggest a time-dependent effect of ischemic preconditioning on 50-m
      swimming performance for competitive athletes, with the time window of the
      beneficial effect starting after about 2-h and lasting for at least 8-h after
      ischemic preconditioning. This change in performance was accompanied by an
      increase in blood lactate accumulation and faster strokes in front crawl.

PMID- 27717654
TI  - Corrigendum to "2nd St. Gallen EORTC Gastrointestinal Cancer Conference:
      Consensus recommendations on controversial issues in the primary treatment of
      rectal cancer" [Eur J Cancer 63 (August 2016) 11-24].

PMID- 27717655
TI  - [Raynaud's phenomenon secondary to anti-glaucoma eye drops].

PMID- 27717656
TI  - Combined effect of permeant and non-permeant cryoprotectants on the quality of
      frozen/thawed chicken sperm.
AB  - The aim of this study was to assess the combined effect of dimethylacetamide
      (DMA) and two non-permeating cryoprotective agents, trehalose and sucrose, on the
      quality of post-thaw chicken semen. Adult Lohmann roosters (n = 27) were used.
      Semen was processed according to the following treatments: Lake pre-freezing
      extender +6% DMA (LPF, control treatment), LPF + 0.1 M trehalose (LPF-T
      treatment), LPF + 0.1 M sucrose (LPF-S treatment) and LPF + 0.1 M trehalose + 0.1
      M sucrose (LPF-TS treatment). Semen was loaded into straws and frozen in nitrogen
      vapour. Sperm quality (viability, mobility and kinetic parameters) was assessed
      immediately after thawing (T0) and at 5 (T5), 10 (T10) and 15 min (T15)
      thereafter. The different cryodiluent combinations significantly affected the
      kinetic parameters. The presence of trehalose, alone or with sucrose, combined
      with DMA improved the quality of motion in cryopreserved sperm in comparison to
      DMA alone (LPF) and DMA with sucrose (LPF-S). In particular, the highest values
      in linearity (LIN) and wobble (WOB) were measured in the treatment LPF-T. The
      treatments significantly affected the recovery rate of progressive motile sperm
      that presented the best value soon after thawing in the LPF-T treatment;
      moreover, the presence of trehalose, alone (LPF-T) or with sucrose (LPF-TS),
      significantly improved the recovery rate of progressive motile sperm also at T5
      and T10 compared to LPF and LPF-S. The present results show a positive synergic
      action of DMA and trehalose on motile function of thawed chicken sperm.

PMID- 27717657
TI  - Explicit and implicit attitude toward an emerging food technology: The case of
      cultured meat.
AB  - Cultured meat is an unfamiliar emerging food technology that could provide a near
      endless supply of high quality protein with a relatively small ecological
      footprint. To understand consumer acceptance of cultured meat, this study
      investigated the influence of information provision on the explicit and implicit
      attitude toward cultured meat. Three experiments were conducted using a Solomon
      four-group design to rule out pretest sensitization effects. The first experiment
      (N = 190) showed that positive or negative information about cultured meat
      changed the explicit attitude in the direction of the information. This effect
      was smaller for participants who were more familiar with cultured meat. In the
      second experiment (N = 194) positive information was provided about solar panels,
      an attitude object belonging to the same sustainable product category as
      sustainable food products such as cultured meat. Positive information about solar
      panels was found to change the explicit attitude in the direction of the
      information. Using mood induction, the third experiment (N = 192) ruled out the
      alternative explanation that explicit attitude change in experiment 1 and 2 was
      caused by content free affect rather than category based inferences. The implicit
      attitude appeared insensitive to both information or mood state in all three
      experiments. These findings show that the explicit attitude toward cultured meat
      can be influenced by information about the sustainability of cultured meat and
      information about a positively perceived sustainable product. This effect was
      shown to be content based rather than merely affect based. Content based
      information in a relevant context could therefore contribute to the commercial
      success of cultured meat.

PMID- 27717659
TI  - Cross relaxation in nitroxide spin labels.
AB  - Cross relaxation, and mI-dependence of the intrinsic electron spin-lattice
      relaxation rate We, are incorporated explicitly into the rate equations for the
      electron-spin population differences that govern the saturation behaviour of 14N-
      and 15N-nitroxide spin labels. Both prove important in spin-label EPR and ELDOR,
      particularly for saturation recovery studies. Neither for saturation recovery,
      nor for CW-saturation EPR and CW-ELDOR, can cross relaxation be described simply
      by increasing the value of We, the intrinsic spin-lattice relaxation rate.
      Independence of the saturation recovery rates from the hyperfine line pumped or
      observed follows directly from solution of the rate equations including cross
      relaxation, even when the intrinsic spin-lattice relaxation rate We is mI
      dependent.

PMID- 27717658
TI  - German version of the Yale Food Addiction Scale 2.0: Prevalence and correlates of
      'food addiction' in students and obese individuals.
AB  - The Yale Food Addiction Scale (YFAS) measures addiction-like eating of palatable
      foods based on the seven diagnostic criteria for substance dependence in the
      fourth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      IV). Most recently, a new version of the YFAS has been developed based on the
      revised eleven diagnostic criteria for substance use disorder in DSM-5. This YFAS
      2.0 was translated into German and used among other measures in a study with 455
      university students (89% female) and in a study with 138 obese patients
      presenting for bariatric surgery (78% female). In the student sample, the one
      factorial structure of the English version could be replicated and internal
      consistency was alpha = 0.90. The diagnostic threshold for 'food addiction' was
      met by 10% of the sample. 'Food addiction' diagnoses were associated with higher
      body mass, binge eating frequency, trait food craving, and attentional
      impulsivity as well as with lower perceived self-regulatory success in dieting.
      In the obese sample, the diagnostic threshold for 'food addiction' was met by 47%
      of participants. Again, 'food addiction' symptomatology was associated with
      higher binge eating frequency and attentional impulsivity. However, those with a
      'food addiction' diagnosis did not differ from those without a diagnosis in body
      mass. To conclude, psychometric properties of the English YFAS 2.0 were
      replicated for the German YFAS 2.0. Prevalence rates and correlates of 'food
      addiction' as measured with the YFAS 2.0 were similar to those found with the
      previous version of the YFAS. Thus, the German YFAS 2.0 appears to be a reliable
      measure that can be used for the investigation of addiction-like eating behavior,
      analogous to the original version of the YFAS and the English YFAS 2.0.

PMID- 27717660
TI  - Portrait of Candida Species Biofilm Regulatory Network Genes.
AB  - Most cases of candidiasis have been attributed to Candida albicans, but Candida
      glabrata, Candida parapsilosis and Candida tropicalis, designated as non-C.
      albicans Candida (NCAC), have been identified as frequent human pathogens.
      Moreover, Candida biofilms are an escalating clinical problem associated with
      significant rates of mortality. Biofilms have distinct developmental phases,
      including adhesion/colonisation, maturation and dispersal, controlled by complex
      regulatory networks. This review discusses recent advances regarding Candida
      species biofilm regulatory network genes, which are key components for
      candidiasis.

PMID- 27717661
TI  - Protective effect of quercetin on homocysteine-induced oxidative stress.
AB  - OBJECTIVE: The aim of this study was to evaluate whether quercetin (QUER)
      treatment could have a protective effect against oxidative stress induced by
      homocysteinemia in rats. MATERIALS AND METHODS: Thirty-two male Sprague-Dawley
      rats (adult) were assigned randomly to four groups: the control group was given
      physiological saline (PS; 1.5 mL/d); the QUER group was given QUER (50 mg/kg body
      weight [BW] daily) in distilled water and 0.25 mL PS; the homocysteine (HCY)
      group was given HCY (1 mg/kg BW daily) in distilled water and 1.25 mL PS; and the
      QUER + HCY group was given QUER 1 h before the administration of HCY. QUER, HCY,
      and PS were injected intraperitoneally every other day for 30 d. Plasma
      malondialdehyde (MDA), carbonyl, erythrocyte-reduced glutathione (GSH), plasma
      sulphydril (-SH) levels, erythrocyte catalase (CAT), and superoxide dismutase
      (SOD) activities were determined. RESULTS: Plasma CAT levels in the QUER group
      were found to be significantly higher than in the control group, whereas plasma
      MDA levels in the QUER group significantly decreased compared with the control
      group. In the HCY group, plasma MDA and carbonyl levels significantly increased
      and GSH and SOD levels significantly decreased compared with the control group.
      Plasma MDA levels significantly decreased and GSH and CAT levels significantly
      increased in the QUER + HCY group compared with the HCY group. Plasma -SH levels
      were significantly lower in the HCY group than in the control group. Plasma -SH
      levels were higher in the QUER + HCY group than in the HCY group, but they were
      not significant. CONCLUSION: The exposure of rats to HCY leads to oxidative
      stress reflected in increased MDA and decreased antioxidant enzyme levels.
      Administration of QUER might attenuate oxidative damage induced by HCY or have a
      protective effect against it.

PMID- 27717662
TI  - The most effective factors to offset sarcopenia and obesity in the older Korean:
      Physical activity, vitamin D, and protein intake.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of the types and
      levels of physical activity in conjunction with protein intake and vitamin D on
      sarcopenia and obesity status in an elderly population. METHODS: Study
      participants (N = 4452) were ages >=60 y and included 1929 men and 2523 women who
      completed a body composition analysis with a dual energy x-ray absorptiometry and
      provided health and dietary data. RESULTS: Higher appendicular skeletal muscle
      mass/weight was observed in the non-obese group, although obese participants had
      greater weights. The non-obese sarcopenia subgroup showed health problems related
      to insulin resistance and metabolic-related factors compared with the
      nonsarcopenic group. The total metabolic equivalent was significantly different
      in both obese categories, regardless of sarcopenic status. The prevalence of
      obesity, sarcopenia, and sarcopenic obesity relatively increased with a diet
      deficient of protein intake and vitamin D. CONCLUSION: These data suggest that
      sarcopenia had a significant association with metabolic-related factors; physical
      activity, especially vigorous activity; and protein intake and vitamin D levels
      in a non-obese elderly population. Therefore, maintaining healthy body weight by
      means of resistance exercise and enhanced protein intake and vitamin D may help
      offset sarcopenia in this age group.

PMID- 27717663
TI  - Fuzhuan tea reverses arterial stiffening after modest weight gain in mice.
AB  - OBJECTIVES: The aim of this study was to examine the effects of a Western diet
      (WD) and supplementation with Fuzhuan tea on large artery stiffness, as
      determined by aortic pulse wave velocity (aPWV). METHODS: Mice were subjected to
      a standard diet (SD; n = 12) or WD (n = 10) for 7 mo, and were then separated to
      receive nonsupplemented drinking water (SD-W and WD-W) or water supplemented with
      Fuzhuan tea (SD-T and WD-T) (200 mg/kg daily); mice were then maintained on their
      respective diets for an additional 2 mo. RESULTS: After the initial 7-mo feeding
      period, WD elicited a modest and significantly greater increase in body weight
      than did SD (39.6 +/- 0.71 versus 34.5 +/- 1.16 g; P < 0.01). PWV was
      significantly elevated in WD but not in SD (459.3 +/- 4.8 versus 422.4 +/- 6.4
      cm/s; P < 0.001). Following an additional 2 mo, PWV continued to increase in WD
      W, but returned to control levels in WD-T (WD-W: 519.8 +/- 12.8; WD-T: 426.5 +/-
      18.6; SD-W: 429.7 +/- 8.6; SD-T: 429.1 +/- 6.1 cm/s; P < 0.001, WD-W versus all
      groups). The increase in PWV in WD-W was accompanied by an increase in aortic
      collagen (WD-W: 38.8 +/- 4.6 versus SD-W: 17.5 +/- 5.1 percent cross-sectional
      area; P < 0.05). CONCLUSION: The results of the present study suggest that the
      increase in arterial stiffness after modest, diet-induced weight gain can be
      reversed by supplementation with Fuzhuan tea.

PMID- 27717664
TI  - Objective measures of sleep quality have not declined over the last 50 years.

PMID- 27717666
TI  - Neutralizing capacity of monoclonal and polyclonal anti-natalizumab antibodies:
      The immune response to antibody therapeutics preferentially targets the antigen
      binding site.

PMID- 27717665
TI  - Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway
      hyperreactivity and requires inducible T-cell costimulator-inducible T-cell
      costimulator ligand interaction.
AB  - BACKGROUND: Atopic diseases, including asthma, exacerbate type 2 immune responses
      and involve a number of immune cell types, including regulatory T (Treg) cells
      and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent
      producers of type 2 cytokines, the regulation of ILC2 activation and function is
      not well understood. OBJECTIVE: In the present study, for the first time, we
      evaluate how Treg cells interact with pulmonary ILC2s and control their function.
      METHODS: ILC2s and Treg cells were evaluated by using in vitro suppression
      assays, cell-contact assays, and gene expression panels. Also, human ILC2s and
      Treg cells were adoptively transferred into NOD SCID gammaC-deficient mice, which
      were given isotype or anti-inducible T-cell costimulator ligand (ICOSL)
      antibodies and then challenged with IL-33 and assessed for airway
      hyperreactivity. RESULTS: We show that induced Treg cells, but not natural Treg
      cells, effectively suppress the production of the ILC2-driven proinflammatory
      cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data
      reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell
      contact for Treg cell-mediated ILC2 suppression alongside the suppressive
      cytokines TGF-beta and IL-10. Using a translational approach, we then demonstrate
      that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to
      control airway inflammation in a humanized ILC2 mouse model. CONCLUSION: These
      findings suggest that peripheral expansion of induced Treg cells can serve as a
      promising therapeutic target against ILC2-dependent asthma.

PMID- 27717668
TI  - Epinephrine for resuscitation: A century of use and decades of doubts. Let's look
      to the real physiological response, now!

PMID- 27717669
TI  - The LGI1-ADAM22 protein complex in synaptic transmission and synaptic disorders.
AB  - Physiological functioning of the brain requires fine-tuned synaptic transmission,
      and its dysfunction causes various brain disorders such as autism, dementia, and
      epilepsy. It is therefore extremely important to identify and characterize key
      regulators of synaptic function. In particular, disease-related synaptic
      proteins, such as autism-related neurexin-neuroligin and psychiatric disorder
      related NMDA receptor, have attracted considerable attention. Recent basic and
      clinical research has highlighted critical roles of a ligand-receptor complex,
      LGI1-ADAM22, in synaptic transmission and brain function, as mutations in the
      LGI1 gene cause autosomal dominant lateral temporal lobe epilepsy and
      autoantibodies to LGI1 cause limbic encephalitis which is characterized by memory
      loss and seizures. Here, we will review our current knowledge about LGI1 and
      ADAM22, and discuss their patho-physiological roles in synaptic transmission and
      synaptic disorders.

PMID- 27717667
TI  - Global tobacco prevention and control in relation to a cardiovascular health
      promotion and disease prevention framework: A narrative review.
AB  - The purpose of this review is to emphasize the role of tobacco prevention and
      control in cardiovascular health (CVH) promotion and cardiovascular disease (CVD)
      prevention, including the importance of these endpoints for measuring the full
      impact of tobacco-related policies, programs, and practices. In this review, we
      describe an overview of tobacco control interventions that have led to
      substantial declines in tobacco use and the relationship between these declines
      with CVH and CVD. We review interventions that have had success in high-income
      countries (HICs) as well as those that are gaining traction in low- and middle
      income countries (LMICs). We emphasize the challenges to comprehensive tobacco
      prevention and control strategies faced by LMICs, and highlight the special role
      of cardiovascular health professionals in achieving CVH promotion and CVD
      prevention endpoints through tobacco control. Tobacco prevention and control
      strategies have a strong scientific basis, yet a distinct gap remains between
      this evidence and implementation of tobacco control policies, particularly in
      LMICs. Health professionals can contribute to tobacco control efforts, especially
      through patient-level clinical interventions, when supported by a health care
      system and government that recognize and support tobacco control as a critical
      strategy for CVH promotion and CVD prevention. Understanding, supporting, and
      applying current and evolving policies, programs, and practices in tobacco
      prevention and control is the province of all health professionals, especially
      those concerned with CVH promotion and CVD prevention. A new tobacco control
      roadmap from the World Heart Federation provides a strong impetus to the needed
      interdisciplinary collaboration.

PMID- 27717670
TI  - Formation and disruption of functional domains in myelinated CNS axons.
AB  - Communication in the central nervous system (CNS) occurs through initiation and
      propagation of action potentials at excitable domains along axons. Action
      potentials generated at the axon initial segment (AIS) are regenerated at nodes
      of Ranvier through the process of saltatory conduction. Proper formation and
      maintenance of the molecular structure at the AIS and nodes are required for
      sustaining conduction fidelity. In myelinated CNS axons, paranodal junctions
      between the axolemma and myelinating oligodendrocytes delineate nodes of Ranvier
      and regulate the distribution and localization of specialized functional
      elements, such as voltage-gated sodium channels and mitochondria. Disruption of
      excitable domains and altered distribution of functional elements in CNS axons is
      associated with demyelinating diseases such as multiple sclerosis, and is likely
      a mechanism common to other neurological disorders. This review will provide a
      brief overview of the molecular structure of the AIS and nodes of Ranvier, as
      well as the distribution of mitochondria in myelinated axons. In addition, this
      review highlights important structural and functional changes within myelinated
      CNS axons that are associated with neurological dysfunction.

PMID- 27717671
TI  - Tuft Cells: New Players in Colitis.
AB  - A recent surge of interest in tuft cells, which are chemosensory intestinal
      epithelial cells, has uncovered new functional roles for these cells in
      colorectal cancer, metabolic signaling, and type 2 immunity. Here, we explore
      emerging evidence suggesting that tuft cells are critical for protection during
      enteric infections and inflammatory responses.

PMID- 27717672
TI  - [Congenital "kissing" lesions: Nevus or "cafe au lait" spot?]
AB  - INTRODUCTION: "Cafe au lait" spots (CLS) are pigmented skin lesions principally
      located at the trunk and the limbs. Histologically, CLSs consist in an excessive
      pigmentation of the epidermis, with no risk of malignant transformation. The
      "kissing" nevus is a rare pigmented congenital nevus affecting both lower and
      upper eyelids in a mirror layout. As other nevi, it presents a theoretical risk
      of malignant transformation. These two pigmented lesions are responsible for
      aesthetic discomfort when affecting the face. OBSERVATION: Three patients
      presenting with a congenital pigmented lesion affecting the two eyelids in a
      mirror layout are presented. In two cases, the lesions, initially considered as
      "kissing" nevi, were classified as CLSs. The diagnosis of CLS was made on a
      biopsy in one patient and after surgery in the other one. DISCUSSION: Pigmented
      mirror layout lesions, called "kissing" lesions, are exclusively described for
      the nevi. We describe two cases of CLSs affecting the eyelids in a mirror layout.
      Difficulties in diagnostic are exposed and the possible treatments are discussed.

PMID- 27717673
TI  - Primary hydatid cyst of the neck: A rare and unusual site.
AB  - INTRODUCTION: Isolated parasitic swellings of the neck, particularly hydatid
      cysts, are rare, even in endemic countries. The aim of this study was to assess
      the epidemiological and clinical features and the diagnostic approach to head and
      neck hydatid disease. CASE REPORT: A 3-year-old boy was hospitalised for an
      isolated mass of the left side of the neck that had been gradually enlarging for
      one year. Neck ultrasound demonstrated a hypoechoic cystic structure on the
      lateral aspect of the neck, measuring 3.5cm in diameter. Histological examination
      of the surgical specimen confirmed the diagnosis of hydatid cyst. DISCUSSION: In
      endemic countries, a diagnosis of hydatid disease should be suspected in all
      cystic masses of the neck. Epidemiological, clinical, laboratory and radiological
      features can lead to a presumptive diagnosis of hydatid cyst and aspiration
      cytology can correct an erroneous diagnosis. Histological examination confirms
      the diagnosis in these unusual sites.

PMID- 27717674
TI  - Assessing the success of invasive species prevention efforts at changing the
      behaviors of recreational boaters.
AB  - Aquatic invasive species (AIS) pose major conservation challenges in freshwater
      ecosystems. In response, conservation organizations invest considerable resources
      in outreach to encourage AIS prevention behaviors among recreational boaters.
      Despite this, remarkably little is known about whether these efforts catalyze
      significant changes in boaters' perceptions, or whether they cause changes in
      behaviors that reduce AIS risk. We interviewed managers at the 14 Illinois
      organizations active in AIS outreach to determine regional priorities for, and
      investment in, AIS outreach. The results show a network of collaboration that
      reinforces a limited set of conservation messages. Next, we surveyed 515
      recreational boaters to evaluate access to outreach, knowledge of AIS, and
      consistency of prevention behavior. Boater recognition of prevention slogans and
      knowledge of AIS and AIS prevention behavior was similar across Illinois regions
      despite large regional differences in investment in outreach. Most boaters (94%)
      report never intentionally moving organisms among waterbodies. Fewer reported
      that they Always perform recommended actions to reduce risk of AIS spread on
      their boat interior (68%), boat exterior (63%), or fishing tackle (47%).
      Recognition of prevention slogans and the number of AIS recognized were
      significantly, positively, associated with Always performing AIS prevention
      behavior on the vectors of the boat exterior, and fishing tackle, respectively.
      Our results suggest that increasing knowledge may be a necessary condition for
      higher adoption of AIS prevention behaviors, but that this alone may not be
      sufficient. Instead, efforts targeted at boaters who do not currently practice
      the recommended actions are likely to be necessary.

PMID- 27717675
TI  - Formaldehyde removal from wastewater and air by using UV, ferrate(VI) and
      UV/ferrate(VI).
AB  - Formaldehyde removal from an air stream absorbed into a water stream in a packed
      bed continuously and then removed by employing a combination of UV and
      ferrate(VI) as a highly-powerful oxidant in a continuous stirred tank. In
      addition, the removal of formaldehyde from water was investigated in both batch
      and continuous modes. The results of the study performed on formaldehyde
      contaminated water treatment can be used for both air and water treatment process
      design. The primary objective of this study is to compare the performance of
      using UV and ferrate(VI) individually with that of using UV/ferrate(VI)
      simultaneously to remove formaldehyde from both air and water. Moreover, the
      effects of several factors such as pH, ferrate(VI) concentration and temperature
      on formaldehyde removal from water using ferrate(VI) method were evaluated. The
      results of the current study in batch condition showed that the best initial pH
      and ferrate(VI) concentration to obtain the highest formaldehyde removal are 2
      and 1 mg/l, respectively. The results of this part of research also reveal that
      temperatures rise from 25  degrees C to 50  degrees C increases formaldehyde
      removal from 69% to 97%; however, further increase in temperature has an adverse
      effect on removal efficiency. The combination of UV and ferrate(VI) enhances
      formaldehyde removal efficiency to very close to 100% within 35 min. In
      continuous air stream treatment, maximum formaldehyde removal of 94% was obtained
      by using a packed bed scrubber with gas over liquid flow rates ratio of 1.28
      m3/m3. Although the results of this study shows that ferrate(VI) method for
      removal of formaldehyde can be considered as a promising alternative for both
      water and air treatment, further economic studies are required for this process
      to be commercialized.

PMID- 27717676
TI  - An enhanced approach for the use of satellite-derived leaf area index values in
      dry deposition modeling in the Athabasca oil sands region.
AB  - In the Athabasca oil sands region (AOSR) of Northern Alberta, the dry deposition
      of sulphur and nitrogen compounds represents a major fraction of total (wet plus
      dry) deposition due to oil sands emissions. The leaf area index (LAI) is a
      critical parameter that affects the dry deposition of these gaseous and
      particulate compounds to the surrounding boreal forest canopy. For this study,
      LAI values based on Moderate Resolution Imaging Spectroradiometer satellite
      imagery were obtained and compared to ground-based measurements, and two
      limitations with the satellite data were identified. The satellite LAI data
      firstly represents one-sided LAI values that do not account for the enhanced LAI
      associated with needle leaf geometry, and secondly, underestimates LAI in winter
      time northern latitude regions. An approach for adjusting satellite LAI values
      for different boreal forest cover types, as a function of time of year, was
      developed to produce more representative LAI values that can be used by air
      quality sulphur and nitrogen deposition models. The application of the approach
      increases the AOSR average LAI for January from 0.19 to 1.40, which represents an
      increase of 637%. Based on the application of the CALMET/CALPUFF model system,
      this increases the predicted regional average dry deposition of sulphur and
      nitrogen compounds for January by factors of 1.40 to 1.30, respectively. The
      corresponding AOSR average LAI for July increased from 2.8 to 4.0, which
      represents an increase of 43%. This increases the predicted regional average dry
      deposition of sulphur and nitrogen compounds for July by factors of 1.28 to 1.22,
      respectively. These findings reinforce the importance of the LAI metric for
      predicting the dry deposition of sulphur and nitrogen compounds. While satellite
      data can provide enhanced spatial and temporal resolution, adjustments are
      identified to overcome associated limitations. This work is considered to have
      application for other deposition model studies where dry deposition represents a
      significant fraction of total deposition.

PMID- 27717677
TI  - An efficient and economical treatment for batik textile wastewater containing
      high levels of silicate and organic pollutants using a sequential process of
      acidification, magnesium oxide, and palm shell-based activated carbon
      application.
AB  - Considering the chemical properties of batik effluents, an efficient and
      economical treatment process was established to treat batik wastewater containing
      not only high levels of Si and chemical oxygen demand (COD), but also toxic heavy
      metals. After mixing the effluents obtained from the boiling and soaking steps in
      the batik process, acidification using concentrated hydrochloric acid (conc. HCl)
      was conducted to polymerize the silicate under acidic conditions. Consequently,
      sludge was produced and floated. XRD and FT-IR analyses showed that wax molecules
      were coordinated by hydrogen bonding with silica (SiO2). The acidification
      process removed ~78-95% of COD and ~45-50% of Si, depending on the pH. In the
      next stage, magnesium oxide (MgO) was applied to remove heavy metals completely
      and almost 90% of the Si in the liquid phase. During this step, about 70% of COD
      was removed in the hydrogel that arose as a consequence of the crosslinking
      characteristics of the formed nano-composite, such as magnesium silicate or
      montmorillonite. The hydrogel was composed mainly of waxes with polymeric
      properties. Then, the remaining Si (~300 mg/L) in the wastewater combined with
      the effluents from the rinsing steps was further treated using 50 mg/L MgO. As a
      final step, palm-shell activated carbon (PSAC) was used to remove the remaining
      COD to < 50 mg/L at pH 3. Overall, the sequential process of acidification and
      MgO/PSAC application developed could serve as an economical and effective
      treatment option for treating heavily polluted batik effluents.

PMID- 27717679
TI  - Cancer heterogeneity and imaging.
AB  - There is interest in identifying and quantifying tumor heterogeneity at the
      genomic, tissue pathology and clinical imaging scales, as this may help better
      understand tumor biology and may yield useful biomarkers for guiding therapy
      based decision making. This review focuses on the role and value of using x-ray,
      CT, MRI and PET based imaging methods that identify, measure and map tumor
      heterogeneity. In particular we highlight the potential value of these techniques
      and the key challenges required to validate and qualify these biomarkers for
      clinical use.

PMID- 27717678
TI  - Results of application of the ISPD guidelines to the management of peritoneal
      dialysis in a single center in Sudan.
AB  - The culture negative peritonitis in Sudan 2010 was 46% exceeding 20% of the
      recommended ISPD (International Society for Peritoneal Dialysis) guidelines. This
      study reports an update after applying the standard ISPD protocol. The routine
      method was replaced by ISPD protocol. The culture negative rate using the ISPD
      guidelines dropped from 46% in the year 2010, to 39% in the year 2011, to 5% in
      the 2012 and to zero percent in the year 2013. Bacterial and fungal species
      represent (86.76%) and (13.23%) of infection and most isolates showed low
      resistance rate to antibiotics. Touch contamination added significantly
      (p=0.0006) to the risk of contracting Peritonitis. The risk of contracting
      Peritonitis was 1.53 times higher in the group exposed by touch contamination.
      None of the other risk factors contributed significantly to Peritonitis. The
      study highlights the importance of implementing high hygiene practice.

PMID- 27717680
TI  - Social Determinants of Geriatric Depression.

PMID- 27717681
TI  - Efficiency of the Penumbra 5MAX ACE Reperfusion Catheter in Acute Ischemic Stroke
      Patients.
AB  - OBJECTIVE: This study was performed to investigate whether the Penumbra 5MAX ACE
      is superior to other Penumbra systems. MATERIALS AND METHODS: We performed a
      retrospective, single center analysis of patients with acute ischemic stroke with
      occlusion of the internal carotid artery or middle cerebral artery (M1 segment)
      who underwent endovascular therapy using a Penumbra system. The reperfusion
      success rate, puncture-to-revascularization time, and number of passes were
      assessed. Multivariate regression analysis was conducted to evaluate independent
      factors related to revascularization within 60 minutes. Successful
      revascularization was defined by a thrombolysis in cerebral infarction score
      >=2b. RESULTS: The Penumbra 5MAX ACE was used in 24 of the 40 patients (60%).
      Although the revascularization success rate was similar between patient groups (P
      = .229), the number of passes was significantly lower (1.5 +/- .8 versus 2.6 +/-
      1.3, P = .006) and the puncture-to-revascularization time was shorter (50 +/- 26
      minutes versus 116 +/- 69 minutes, P = .002) in patients treated with the
      Penumbra 5MAX ACE. The Penumbra 5MAX ACE was identified as an independent factor
      for early revascularization (odds ratio, 5.80; P = .041). Among patients with a
      premorbid modified Rankin Scale score of 0-1, a modified Rankin Scale score of 0
      2 at 3 months was observed in 15 of the 19 patients (79%) treated with the
      Penumbra 5MAX ACE and in 8 of the 16 (50%) who were not (P = .072). CONCLUSION:
      Acute revascularization therapy using the Penumbra 5MAX ACE can achieve rapid
      successful recanalization and tend to improve clinical outcomes.

PMID- 27717682
TI  - Exome Sequencing Identified CCER2 as a Novel Candidate Gene for Moyamoya Disease.
AB  - The etiology of Moyamoya disease (MMD) is still largely unclear, despite
      identification of RNF213 as the most significant susceptibility gene in East
      Asian patients. Following up our previous study confirming genetic heterogeneity
      in Japanese patients with MMD, we extensively surveyed novel candidate genes for
      a new perspective on the etiology of this disease. Two characteristic pedigrees
      without susceptibility variants in RNF213 were selected for whole-exome
      sequencing; 1 harbored 3 affected members, and the other included discordant
      monozygotic twins. In the former pedigree, 12 rare mutations in 12 genes were co
      segregated with MMD. One of the most deleterious amino acid changes among these
      was p.T76_G80delinsPS in CCER2, which was also mutated in the latter pedigree
      (p.E242K), although the unaffected twin sister shared the same mutation
      reflecting reduced penetrance. These CCER2 mutations were predicted to promote
      aggregation or oligomerization of their protein product, using in silico
      functional analysis. Subsequent CCER2 re-sequencing in an additional 135 MMD
      probands identified 1 recurrent and an additional 2 in-frame insertion-deletion
      mutations, recurrent p.T76_G80delinsPS, p.H218_H220del, and p.E299del. Although
      CCER2 molecular function is not well characterized, it is a secretory protein
      expressed in the brain; therefore, it constitutes a potential biomarker of MMD.

PMID- 27717684
TI  - Second pancreatectomy for recurrent pancreatic ductal adenocarcinoma in the
      remnant pancreas: A pooled analysis.
AB  - OBJECTIVES: The aim of this study was to examine the outcomes of second
      pancreatectomy for the treatment of recurrent pancreatic ductal adenocarcinoma
      (PDAC) in the remnant pancreas. METHOD: Search of the PubMed database was
      undertaken to identify relevant English language studies. Pooled individually
      data were examined for clinical outcomes after second pancreatectomy for
      recurrent PDAC. RESULTS: A total of 19 articles involving 55 patients were
      eligible for inclusion. The median disease-free interval after initial resection
      was 33 (range 7-143) months. Of the 55 patients reported, 52 (94.5%) patients
      underwent completion total pancreatectomy in the second operation for
      recurrences, including 15 patients who developed recurrences more than 5 years
      after the initial operation. There was no perioperative death. The 1-, 3- and 5
      year overall survival rate after the second pancreatectomy was 82.2%, 49.2% and
      40.6% respectively. CONCLUSION: Second pancreatectomy for recurrent PDAC can be
      performed safely with long-term survival in selected patients.

PMID- 27717683
TI  - Unattended Hospital and Home Sleep Apnea Testing Following Cerebrovascular
      Events.
AB  - BACKGROUND: Home sleep apnea testing (HSAT) is an alternative to polysomnography
      for the detection of obstructive sleep apnea (OSA). We assessed the feasibility
      of HSAT as an unattended screening tool for patients with a stroke or transient
      ischemic attack (TIA). AIMS: The primary outcome was the feasibility of
      unattended HSAT, as defined by analyzability of the data. Secondary outcomes
      included determining (1) predictors of obtaining nonanalyzable sleep data and (2)
      time to OSA detection and continuous positive airway pressure (CPAP) initiation.
      METHODS: In this single-center prospective observational study, inpatients or
      outpatients who had sustained a stroke or TIA were screened for OSA using the
      ApneaLink Plus ambulatory sleep monitor in their home or hospital room. RESULTS:
      There were 102 patients who completed unattended sleep monitoring. Mean age was
      68.7 +/- 13.7 years, 55.9% were male, 57.8% were outpatients, and 77.5% had a
      stroke (22.5% with TIA). Eighty-two (80.4%) patients obtained four or more hours
      of analyzable sleep data. Functional dependence (defined as a modified Rankin
      Scale of >2) and elevated body mass index were independently associated with
      obtaining nonanalyzable data. OSA was detected in 63.4% (52 of 82) of patients
      and, of those, 34 of 52 (65.4%) initiated CPAP therapy. The mean time from study
      recruitment to HSAT was 1.7 days (median: 1, interquartile range [IQR]: 2) and
      CPAP was initiated on average within 62.7 days of recruitment (median: 53, IQR:
      30). CONCLUSIONS: Unattended HSAT can be feasibly implemented after stroke or
      TIA. This method facilitates rapid diagnosis and management of OSA in both the
      outpatient and inpatient settings.

PMID- 27717685
TI  - A transgenic rat hepatocyte - Kupffer cell co-culture model for evaluation of
      direct and macrophage-related effect of poly(amidoamine) dendrimers.
AB  - Increasing number of papers demonstrate that Kupffer cells (KCs) play a role in
      the development of drug induced liver injury (DILI). Furthermore, elevated
      intracellular Ca2+ level of hepatocytes is considered as a common marker of DILI.
      Here we applied an in vitro model based on hepatocyte mono- and hepatocyte/KC co
      cultures (H/KC) isolated from transgenic rats stably expressing the GCaMP2
      fluorescent Ca2+ sensor protein to investigate the effects of polycationic (G5),
      polyanionic (G4.5) and polyethylene-glycol coated neutral (G5 Peg) dendrimers
      known to accumulate in the liver, primarily in KCs. Following dendrimer exposure,
      hepatocyte homeostasis was measured by MTT cytotoxicity assay and by Ca2+
      imaging, while hepatocyte functions were studied by CYP2B1/2 inducibility, and
      bilirubin and taurocholate transport. G5 was significantly more cytotoxic than
      G4.5 for hepatocytes and induced Ca2+ oscillation and sustained Ca2+ signals at
      1MUM and10 MUM, respectively both in hepatocytes and KCs. Dendrimer-induced Ca2+
      signals in hepatocytes were attenuated by macrophages. Activation of KCs by
      lipopolysaccharide and G5 decreased the inducibility of CYP2B1/2, which was
      restored by depleting the KCs with gadolinium-chloride and pentoxyphylline,
      suggesting a role of macrophages in the hindrance of CYP2B1/2 induction by G5 and
      lipopolysaccharide. In the H/KC, but not in the hepatocyte mono-culture, G5
      reduced the canalicular efflux of bilirubin and stimulated the uptake and
      canalicular efflux of taurocholate. In conclusion, H/KC provides a good model for
      the prediction of hepatotoxic potential of drugs, especially of nanomaterials
      known to be trapped by macrophages, activation of which presumably contributes to
      DILI.

PMID- 27717687
TI  - Editorial Comment.

PMID- 27717686
TI  - Reconsidering the role of glial cells in chronic stress-induced dopaminergic
      neurons loss within the substantia nigra? Friend or foe?
AB  - Exposure to psychological stress is known to seriously disrupt the operation of
      the substantia nigra (SN) and may in fact initiate the loss of dopaminergic
      neurons within the SN. In this study, we aimed to investigate how chronic stress
      modified the SN in adult male mice. Using a paradigm of repeated restraint stress
      (an average of 20h per week for 6weeks), we examined changes within the SN using
      western blotting and immunohistochemistry. We demonstrated that chronic stress
      was associated with a clear loss of dopaminergic neurons within the SN. The loss
      of dopaminergic neurons was accompanied by higher levels of oxidative stress
      damage, indexed by levels of protein carbonylation and strong suppression of both
      microglial and astrocytic responses. In addition, we demonstrated for the first
      time, that chronic stress alone enhanced the aggregation of alpha-synuclein into
      the insoluble protein fraction. These results indicate that chronic stress
      triggered loss of dopaminergic neurons by increasing oxidative stress,
      suppressing glial neuroprotective functions and enhancing the aggregation of the
      neurotoxic protein, alpha-synuclein. Collectively, these results reinforce the
      negative effects of chronic stress on the viability of dopaminergic cells within
      the SN.

PMID- 27717688
TI  - Editorial Comment.

PMID- 27717689
TI  - Editorial Comment.

PMID- 27717690
TI  - Editorial Comment.

PMID- 27717691
TI  - Reply by Authors.

PMID- 27717692
TI  - Editorial Comment.

PMID- 27717694
TI  - Reply by Authors.

PMID- 27717693
TI  - Editorial Comment.

PMID- 27717695
TI  - B cells of multiple sclerosis patients induce autoreactive proinflammatory T cell
      responses.
AB  - Antibody-independent B cell functions play an important role in multiple
      sclerosis (MS) pathogenesis. In this study, B cell antigen presentation and
      costimulation in MS were studied. Peripheral blood B cells of MS patients showed
      increased expression of costimulatory CD86 and CD80 molecules compared with
      healthy controls (HC). In MS cerebrospinal fluid (CSF), 12-fold and 2-fold
      increases in CD86+ and CD80+ B cells, respectively, were evidenced compared with
      peripheral blood. Further, B cells from MS patients induced proinflammatory T
      cells in response to myelin basic protein (MBP). Immunomodulatory treatment
      restored B cell costimulatory molecule expression and caused significantly
      reduced B cell induced T cell responses. Together, these results demonstrate the
      potential of B cells from MS patients to induce autoreactive proinflammatory T
      cell responses. Immunomodulatory therapy abrogated this effect, emphasizing the
      importance of B cell antigen presentation and costimulation in MS pathology.

PMID- 27717697
TI  - Puerarin protects against cadmium-induced proximal tubular cell apoptosis by
      restoring mitochondrial function.
AB  - Puerarin (PU) is a potent free radical scavenger with a protective effect in
      nephrotoxin-mediated oxidative damage. Here, we show a novel molecular mechanism
      by which PU exerts its anti-apoptotic effects in cadmium (Cd)-exposed primary rat
      proximal tubular (rPT) cells. Morphological assessment and flow cytometric
      analysis revealed that PU significantly decreased Cd-induced apoptotic cell death
      of rPT cells. Administration of PU protected cells against Cd-induced depletion
      of mitochondrial membrane potential (DeltaPsim) and lipid peroxidation. Cd
      mediated mitochondrial permeability transition pore (MPTP) opening, disruption of
      mitochondrial ultrastructure, mitochondrial cytochrome c (cyt-c) release, caspase
      3 activation and subsequently poly ADP-ribose polymerase (PARP) cleavage could be
      effectively blocked by the addition of PU. Moreover, up-regulation of Bcl-2 and
      down-regulation of Bax and hence increased Bcl-2/Bax ratio were observed with the
      PU administration. In addition, PU reversed Cd-induced ATP depletion by restoring
      DeltaPsim to affect ATP production and by regulating expression levels of ANT-1
      and ANT-2 to improve ATP transport. In summary, PU inhibited Cd-induced apoptosis
      in rPT cells by ameliorating the mitochondrial dysfunction.

PMID- 27717698
TI  - Asparagus adscendens root extract enhances cognition and protects against
      scopolamine induced amnesia: An in-silico and in-vivo studies.
AB  - Asparagus adscendens Roxb. commonly known as safed musli and belonging to the
      Liliaceae family is cultivated mainly in Asian countries. In traditional
      medicine, safed musli is recommended as nerve tonic and remedy for memory
      impairment. The present study was aimed to evaluate nootropic and antiamnesic
      activities of Asparagus adscendens extract (AAE) using in silico and in vivo
      approach. Phytoconstituents of A. adscendens root reported in literature were
      subjected to in silico prediction using PASS and Pharmaexpert. The radial arm
      maze and passive shock avoidance paradigm were employed to evaluate nootropic
      activity. Subsequently, the anti-amnesic activity was evaluated in scopolamine
      induced amnesia model. To elucidate the mechanism of nootropic activity, the
      effect of AAE on the activities of acetylcholinesterase and antioxidant enzymes
      in the cortex and hippocampus of mice were also evaluated. In silico activity
      spectrum for all of A. adscendens phytoconstituents exhibited excellent
      prediction score for nootropic activity. Pretreatment with AAE (50, 100 & 200
      mg/kg, i.p.) for 15 days showed significant decrease in working memory error,
      reference memory error and retrieval latency in radial arm maze and decrease in
      step down latency in passive shock avoidance paradigm were observed. Further, AAE
      significantly reduced acetylcholinesterase and oxidative stress parameters in
      cortex and hippocampus of mice. Thus, in silico and in vivo results suggest that
      A. adscendens root may exert its nootropic activity through both anti
      acetylcholinesterase and antioxidant activities.

PMID- 27717699
TI  - Chronic MeHg exposure modifies the histone H3K4me3 epigenetic landscape in
      Caenorhabditis elegans.
AB  - Methylmercury (MeHg) is a persistent environmental pollutant that occurs in the
      food chain, at occupational sites, and via medical procedures. Exposure in humans
      and animal models results in renal, neuro, and reproductive toxicities. In this
      study, we demonstrate that chronic exposure to MeHg (10MUM) causes epigenetic
      landscape modifications of histone H3K4 trimethylation (H3K4me3) marks in
      Caenorhabditis elegans using chromatin immuno-precipitation sequencing (ChIP
      seq). The modifications correspond to the locations of 1467 genes with enhanced
      and 508 genes with reduced signals. Among enhanced genes are those encoding
      glutathione-S-transferases, lipocalin-related protein and a cuticular collagen.
      ChIP-seq enhancement of these genes was confirmed with increased mRNA expression
      levels revealed by qRT-PCR. Furthermore, we observed enhancement of H3K4me3 marks
      in these genes in animals exposed to MeHg in utero and assayed at L4 stage. In
      utero exposure enhanced marks without alterations in mRNA expression except for
      the lpr-5 gene. Finally, knockdown of lipocalin-related protein gene lpr-5, which
      is involved in intercellular signaling, and cuticular collagen gene dpy-7,
      structural component of the cuticle, by RNA interference (RNAi) resulted in
      increased lethality of animals after MeHg exposure. Our results provide new data
      on the epigenetic landscape changes elicited by MeHg exposure, as well as
      describe a unique model for studying in utero effects of heavy metals. Together,
      these findings may help to understand the toxicological effects of MeHg at the
      molecular level.

PMID- 27717700
TI  - Influence of temperature and reaction time on the conversion of polystyrene waste
      to pyrolysis liquid oil.
AB  - This paper aims to investigate the effect of temperature and reaction time on the
      yield and quality of liquid oil produced from a pyrolysis process. Polystyrene
      (PS) type plastic waste was used as a feedstock in a small pilot scale batch
      pyrolysis reactor. At 400 degrees C with a reaction time of 75min, the gas yield
      was 8% by mass, the char yield was 16% by mass, while the liquid oil yield was
      76% by mass. Raising the temperature to 450 degrees C increased the gas
      production to 13% by mass, reduced the char production to 6.2% and increased the
      liquid oil yield to 80.8% by mass. The optimum temperature and reaction time was
      found to be 450 degrees C and 75min. The liquid oil at optimum conditions had a
      dynamic viscosity of 1.77mPas, kinematic viscosity of 1.92cSt, a density of
      0.92g/cm3, a pour point of -60 degrees C, a freezing point of -64 degrees C, a
      flash point of 30.2 degrees C and a high heating value (HHV) of 41.6MJ/kg this is
      similar to conventional diesel. The gas chromatography with mass
      spectrophotometry (GC-MS) analysis showed that liquid oil contains mainly styrene
      (48%), toluene (26%) and ethyl-benzene (21%) compounds.

PMID- 27717702
TI  - Characterization of gaseous emissions and ashes from the combustion of furniture
      waste.
AB  - Gaseous emissions and ash obtained in the combustion of furniture waste have been
      studied, with particular emphasis on the emissions of hazardous pollutants, such
      as PCDD/Fs and dl-PCBS. Two different combustion procedures were carried out, one
      of them in a conventional residential stove (without an automatic control of
      combustion air and bad mixing of combustion gases with air), and the other in a
      laboratory-scale reactor (operating under substoichiometric conditions). Three
      different experiments were carried out in the residential stove, in which the
      gaseous emissions and ashes obtained were analysed. The fuel burnt out in two of
      the experiments was furniture wood waste and in one of the experiments, the fuel
      burnt out was briquettes composed of a mixture of furniture wood with 10wt.% of
      polyurethane foam. One of the purposes of these experiments was the evaluation of
      the possible inhibition effect of the higher nitrogen content on the formation of
      PCDD/Fs. Slight inhibition of the PCDD/F formation was found although, it is
      noteworthy that the lowest yield of PAHs, volatile and semi-volatile compounds
      were obtained in the combustion of these briquettes. In all experiments, the
      emission factors of polychlorinated dibenzo-p-dioxins and dibenzofurans and
      dioxin-like polychlorinated biphenyls (PCDD/Fs and dl-PCBs) were between 29 and
      74ng WHO-TEQ/kg sample burnt, lower than that obtained by other authors in the
      burning of pine needles and cones. PCDD/Fs and dl-PCBs emissions from furniture
      wood waste combustion were also analysed in the laboratory scale reactor at 850
      degrees C and the results were compared with the values obtained from the
      combustion of solid wood (untreated wood). The total equivalent toxicity obtained
      was 21.1ng WHO-TEQ/kg sample for combustion of furniture wood waste, which is low
      in comparison with those obtained for other waste combustion in similar
      conditions. In the laboratory scale reactor, PCDFs were the dominant compounds in
      the profiles of PCDD/Fs, by contrast, in the combustion in the residential stove,
      the majority compounds were PCDDs, due to the different operation conditions.

PMID- 27717701
TI  - Techno-economic evaluation of a tandem dry batch, garage-style digestion-compost
      process for remote work camp environments.
AB  - The extraction of natural resources often involves housing workers in remote work
      camps far from population centres. These camps are prevalent in northern Alberta
      where they house approximately 40,000 workers involved in oil sands processing.
      The central, full-service cafeterias at these camps produce a significant
      quantity of food and cardboard waste. Due to their remote nature, these camps
      face high waste disposal costs associated with trucking waste long distances to
      the landfill. In this study, we investigated the techno-economic feasibility of
      on-site treatment of food and cardboard waste in a tandem dry batch, garage-style
      anaerobic digestion-compost process in which the waste material is converted into
      renewable energy used to heat the camp water supply and a nutrient-rich soil
      amendment for local land reclamation projects. Dry batch digestion and windrow
      composting pilot trials were performed on a simulated work camp waste in order to
      assess technical performance. The quality of the final compost was found to meet
      regulatory standards. A complete mass balance was then developed for a facility
      treating 3000 tonnes food waste and 435 tonnes waste cardboard annually. An
      economic assessment of such a facility was performed and, depending on the level
      of capital support and recognition of carbon credits for landfill methane
      mitigation, would require waste disposal costs to be between $115 and $195 CAD
      per tonne to meet financial criteria for project selection in Alberta's oil and
      gas industry.

PMID- 27717703
TI  - Penetrating Keratoplasty Performed by Residents Compared With an Experienced
      Cornea Transplant Surgeon.
AB  - BACKGROUND: Reports on keratoplasty by residents are rare compared to those on
      cataract surgery. The aim of this study was to compare the results and surgery
      time of penetrating keratoplasty performed by residents and an experienced cornea
      surgeon. METHODS: The medical records and surgery videos of the first 5
      penetrating keratoplasty procedures by 4 residents were reviewed and compared
      with those in 20 penetrating keratoplasty procedures by an experienced cornea
      surgeon. Patients underwent penetrating keratoplasty at the Department of
      Ophthalmology, Tokyo Dental College, Chiba, Japan. The main outcome measures are
      graft survival, best-corrected visual acuity, postoperative astigmatism,
      decreased rate of graft endothelial cell density, and details of surgery time.
      RESULTS: Graft survival, best-corrected visual acuity, and postoperative
      astigmatism were not significantly different between residents group and the
      experienced surgeon group. The average decrease of graft endothelial cell density
      owing to surgery in residents and the experienced surgeon were 19.0 +/- 17.5 and
      18.5 +/- 12.1%, respectively (p = 0.27, Mann-Whitney U test). The average surgery
      time taken by residents was 66.9 +/- 18.1 minutes, and that by the experienced
      surgeon it was 28.2 +/- 7.9 minutes (p = 0.0071, Mann-Whitney U test). Residents
      required the most time for running suture technique. CONCLUSIONS: The results of
      keratoplasty by residents were similar with those done by the experienced
      surgeon. Surgery time was the only statistically significant difference (p =
      0.0071), which did not influence surgical results.

PMID- 27717704
TI  - How Informative are the Plastic Surgery Residency Websites to Prospective
      Applicants?
AB  - OBJECTIVE: To evaluate the comprehensiveness of plastic surgery program websites.
      DESIGN: American Medical Association interactive database was accessed for the
      list of integrated plastic surgery programs, in June 2015. Since then, 67 plastic
      surgery program websites were accessed and searched for the presence or absence
      of 31 criteria, which were further grouped into 5 categories: First, program
      contact information; second, training and research; third, program setup; fourth,
      benefits and facilities; and fifth, information for applicants. Programs were
      categorized based on US census bureau designated regions, and number of residency
      positions available. One-way ANOVA test was used for comparison. RESULTS: Only
      25% (17) program website had information available on more than two-thirds (21 or
      more of 31) of the criteria. The 3 least factors commonly available by program
      websites were: operative log (10%), contract (10%), and information on night
      float (25%). The 3 most commonly available factors included: coordinator
      information (92%), number of residents (92%), and comprehensive faculty list
      (88%). Less than 50% of the programs provided information regarding fellowship
      opportunities, active and previous research projects, and operative logs. There
      was no difference in amount of information on program websites when analyzed for
      program size or program geographic location. CONCLUSION: Programs should consider
      revising their websites to include aforementioned 31 criteria. This would make
      applicants and potential resident physicians better informed of the programs
      before the interview process such that they would be more likely to apply to only
      those programs that match their specific aspirations.

PMID- 27717705
TI  - Does the H Index Correlate With Academic Rank Among Full-Time Academic
      Craniofacial Surgeons?
AB  - OBJECTIVE: To assess the relationship between the H index and the academic rank
      among full-time academic craniofacial surgeons. DESIGN: This was a cross
      sectional study of full-time academic craniofacial surgeons. SETTING: Data were
      compiled and analyzed at the Department of Plastic and Reconstructive Surgery,
      Johns Hopkins Hospital. RESULTS: The study sample included 127 full-time academic
      craniofacial surgeons. Overall, 89% were men, the mean number of years since
      completion of training was 16.2 +/- 11.2 years. Most surgeons had a background in
      plastic and reconstructive surgery. Approximately 75% had completed formal
      fellowship training. The mean H index for the sample was 12.4 +/- 9.9. The H
      index was strongly correlated with academic rank (rs = 0.62, p < 0.001). In a
      multiple linear regression model, adjusting for multiple confounders/effect
      modifiers, including number of years since training and total number of
      publications, the H index was significantly associated with academic rank
      (coefficient = 0.33, p = 0.04). CONCLUSIONS: Among full-time academic
      craniofacial surgeons, the H index is strongly correlated with the academic rank.

PMID- 27717706
TI  - Changing the Learning Curve in Novice Laparoscopists: Incorporating Direct
      Visualization into the Simulation Training Program.
AB  - OBJECTIVE: A major challenge in laparoscopic surgery is the lack of depth
      perception. With the development and continued improvement of 3D video
      technology, the potential benefit of restoring 3D vision to laparoscopy has
      received substantial attention from the surgical community. Despite this,
      procedures conducted under 2D vision remain the standard of care, and trainees
      must become proficient in 2D laparoscopy. This study aims to determine whether
      incorporating 3D vision into a 2D laparoscopic simulation curriculum accelerates
      skill acquisition in novices. DESIGN: Postgraduate year-1 surgical specialty
      residents (n = 15) at the Schulich School of Medicine and Dentistry, at Western
      University were randomized into 1 of 2 groups. The control group practiced the
      Fundamentals of Laparoscopic Surgery peg-transfer task to proficiency exclusively
      under standard 2D laparoscopy conditions. The experimental group first practiced
      peg transfer under 3D direct visualization, with direct visualization of the
      working field. Upon reaching proficiency, this group underwent a perceptual
      switch, changing to standard 2D laparoscopy conditions, and once again trained to
      proficiency. RESULTS: Incorporating 3D direct visualization before training under
      standard 2D conditions significantly (p < 0.0.5) reduced the total training time
      to proficiency by 10.9 minutes or 32.4%. There was no difference in total number
      of repetitions to proficiency. Data were also used to generate learning curves
      for each respective training protocol. CONCLUSIONS: An adaptive learning
      approach, which incorporates 3D direct visualization into a 2D laparoscopic
      simulation curriculum, accelerates skill acquisition. This is in contrast to
      previous work, possibly owing to the proficiency-based methodology employed, and
      has implications for resource savings in surgical training.

PMID- 27717707
TI  - Evaluation of Procedural Simulation as a Training and Assessment Tool in General
      Surgery-Simulating a Laparoscopic Appendectomy.
AB  - BACKGROUND: Laparoscopic appendectomy is a commonly performed surgical procedure,
      but few training models have been described for it. We examined a virtual reality
      module for practising a laparoscopic appendectomy. METHODS: A prospective cohort
      study with the following 3 groups of surgeons (n = 45): novices (0 procedures),
      intermediates (10-50 procedures), and experienced (>100 procedures). After being
      introduced to the simulator and 1 familiarization attempt on the procedural
      module, the participants practiced the module 20 times. Movements, task time, and
      procedure-specific parameters were compared over time. RESULTS: The time and
      movement parameters were significantly different during the first attempt, and
      more experienced surgeons used fewer movements and less time than novices (p <
      0.01), although only 2 parameters were significantly different between novices
      and intermediates. All 3 groups improved significantly over 20 attempts (p <
      0.0001). The intraclass correlation coefficient varied between 0.55 and 0.68 and
      did not differ significantly between the 3 groups (p > 0.05). When comparing
      novices with experienced surgeons, novices had a higher risk of burn damage to
      cecum (odds ratio [OR] = 3.0 [95% CI: 1.3; 7.0] p = 0.03), pressure damage to
      appendix (OR = 3.1 [95% CI: 2.0; 4.9] p < 0.0001), and grasping of the appendix
      (OR = 2.9 [95% CI: 1.8; 4.7] p < 0.0001). The risk of causing a perforation was
      not significantly different among the different experience levels (OR = 1.9 [95%
      CI: 0.9; 3.8] p = 0.14). Only 3 out of 5 error parameters differed significantly
      when comparing novices and experienced surgeons. Similarly, when comparing
      intermediates and novices, it was only 2 of the parameters that differed.
      DISCUSSION: The simulator module for practising laparoscopic appendectomy may be
      useful as a training tool, but further development is required before it can be
      used for assessment purposes. Procedural simulation may demonstrate more
      variation for movement parameters, and future research should focus on developing
      better procedure-specific parameters.

PMID- 27717708
TI  - Effect of Home-Call on Otolaryngology Resident Education: A Pilot Study.
AB  - OBJECTIVE: To inform institutional policies regarding call encounters through an
      evaluation of the effect of home-call on academic experience and fatigue among
      surgical residents. This study conducted an assessment of the nature of resident
      call encounters premidnight and postmidnight and a comparative analysis of sleep
      deprivation and efficiency in residents during home-call and off call. DESIGN,
      SETTING, AND PARTICIPANTS: All Otolaryngology-Head and Neck Surgery residents (n
      = 9) at single Canadian institution were asked to establish the time and nature
      of call encounters during home-call. Residents completed the Stanford Sleepiness
      Scale precall and postcall to measure sleepiness and wore an Actigraph device to
      measure sleep efficiency to establish fatigue in the setting of home-call as
      compared with residents off call. Home-call and off call patterns were studied
      using a random computer-generated selection of days for participants in both
      study groups. Analysis was conducted from December 1, 2013 to December 30, 2014.
      RESULTS: Residents received on average 7 pages per night, of which 78.5% of pages
      were for nonurgent issues. On an average, change in sleep deprivation scores
      postcall was 3.0 points higher (95% CI: 2.48-3.57, p < 0.0001) in residents who
      were qualified for a postcall day compared with residents who did not qualify for
      a postcall day and residents off call according to the Stanford Sleepiness Scale.
      Postcall sleep deprivation was significantly associated with number of encounters
      managed after midnight, regardless of management through telephone or in-hospital
      (p = 0.01). The Actigraph device identified a significant decrease in sleep
      efficiency in residents who were qualified for a postcall day compared with
      residents off call (mean = -31.1; 95% CI: -38.9, -23.4; p < 0.001). CONCLUSIONS:
      This is the first study to evaluate surgical residents' home-call experience. We
      identified a high proportion of nonurgent encounters that residents managed on
      call and increased postcall fatigue associated with postmidnight telephone
      encounters. This study highlights the detrimental effects of frequent sleep
      interruptions because of encounters on call and suggests the need for
      institutional guidelines to help minimize these interruptions.

PMID- 27717709
TI  - CNS sites activated by renal pelvic epithelial sodium channels (ENaCs) in
      response to hypertonic saline in awake rats.
AB  - In some patients, renal nerve denervation has been reported to be an effective
      treatment for essential hypertension. Considerable evidence suggests that
      afferent renal nerves (ARN) and sodium balance play important roles in the
      development and maintenance of high blood pressure. ARN are sensitive to sodium
      concentrations in the renal pelvis. To better understand the role of ARN, we
      infused isotonic or hypertonic NaCl (308 or 500mOsm) into the left renal pelvis
      of conscious rats for two 2hours while recording arterial pressure and heart
      rate. Subsequently, brain tissue was analyzed for immunohistochemical detection
      of the protein Fos, a marker for neuronal activation. Fos-immunoreactive neurons
      were identified in numerous sites in the forebrain and brainstem. These areas
      included the nucleus tractus solitarius (NTS), the lateral parabrachial nucleus,
      the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus
      (SON). The most effective stimulus was 500mOsm NaCl. Activation of these sites
      was attenuated or prevented by administration of benzamil (1MUM) or amiloride
      (10MUM) into the renal pelvis concomitantly with hypertonic saline. In
      anesthetized rats, infusion of hypertonic saline but not isotonic saline into the
      renal pelvis elevated ARN activity and this increase was attenuated by
      simultaneous infusion of benzamil or amiloride. We propose that renal pelvic
      epithelial sodium channels (ENaCs) play a role in activation of ARN and, via
      central visceral afferent circuits, this system modulates fluid volume and
      peripheral blood pressure. These pathways may contribute to the development of
      hypertension.

PMID- 27717712
TI  - WITHDRAWN: Improving classification of protein binders for virtual drug screening
      by novel swarm-based feature selection techniques.
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
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 27717711
TI  - BET bromodomain is a novel regulator of TAZ and its activity.
AB  - Transcriptional coactivator with PDZ-binding motif (TAZ) is a key transcriptional
      mediator of Hippo signaling that has been recently reported to mediate Wnt
      activated transcription and serve as a component to suppress canonical Wnt/beta
      catenin activity. The Bromodomain and Extra-terminal domain (BET) family of
      proteins can recognize the acetylated lysine chain on histones and plays a
      critical role in transcriptional regulation. However, the mechanisms underlying
      transcriptional repression by the BET bromodomain are poorly understood. Here, we
      found that BET bromodomain inhibition upregulated TAZ protein and its
      transcriptional output, independent of its well-established role as a mediator of
      Hippo and Wnt signaling. Additionally, JQ1, a synthetic BET inhibitor, suppressed
      Wnt/beta-catenin activity by upregulating TAZ. Although JQ1 upregulated TAZ,
      which is known to promote cell proliferation, it drastically suppressed the
      growth of colon cancer cells by inducing cell cycle arrest. Collectively, our
      study identified an unexpected transcriptional repression function of the BET
      bromodomain and a novel mechanism for TAZ upregulation.

PMID- 27717714
TI  - Esophageal placement of a lumen-apposing metal stent in a patient with a chronic
      anastomotic stricture.

PMID- 27717713
TI  - Biophysical approaches promote advances in the understanding of von Willebrand
      factor processing and function.
AB  - The large multimeric plasma glycoprotein von Willebrand factor (VWF) is essential
      for primary hemostasis by recruiting platelets to sites of vascular injury. VWF
      multimers respond to elevated hydrodynamic forces by elongation, thereby
      increasing their adhesiveness to platelets. Thus, the activation of VWF is force
      induced, as is its inactivation. Due to these attributes, VWF is a highly
      interesting system from a biophysical point of view, and is well suited for
      investigation using biophysical approaches. Here, we give an overview on recent
      studies that predominantly employed biophysical methods to gain novel insights
      into multiple aspects of VWF: Electron microscopy was used to shed light on the
      domain structure of VWF and the mechanism of VWF secretion. High-resolution
      stochastic optical reconstruction microscopy, atomic force microscopy (AFM),
      microscale thermophoresis and fluorescence correlation spectroscopy allowed
      identification of protein disulfide isomerase isoform A1 as the VWF dimerizing
      enzyme and, together with molecular dynamics simulations, postulation of the
      dimerization mechanism. Advanced mass spectrometry led to detailed identification
      of the glycan structures carried by VWF. Microfluidics was used to illustrate the
      interplay of force and VWF function. Results from optical tweezers measurements
      explained mechanisms of the force-dependent functions of VWF's domains A1 and A2
      and, together with thermodynamic approaches, increased our understanding of
      mutation-induced dysfunctions of platelet-binding. AFM-based force measurements
      and AFM imaging enabled exploration of intermonomer interactions and their
      dependence on pH and divalent cations. These advances would not have been
      possible by the use of biochemical methods alone and show the benefit of
      interdisciplinary research approaches.

PMID- 27717715
TI  - A mandibular swelling of long duration.

PMID- 27717716
TI  - Postoperative changes in mandibular position after mandibular setback surgery via
      the surgery-first approach in relation to the increase of vertical dimension and
      the amount of mandibular setback.
AB  - OBJECTIVES: This study aimed to compare preoperatively predicted rotational
      relapse with actual post-treatment mandibular position after mandibular setback
      surgery via the surgery-first approach and to evaluate the effect of the increase
      of vertical dimension (VD) on surgical occlusion and the amount of mandibular
      setback on postoperative mandibular positional changes. STUDY DESIGN: Twenty-nine
      patients who underwent bilateral sagittal split ramus osteotomy for mandibular
      prognathism were evaluated by using lateral cephalograms, which had been obtained
      preoperatively, immediately postoperatively, and immediately after debonding.
      Increase of VD on surgical occlusion was measured preoperatively. We estimated
      the mandibular forward movement resulting from the postoperative mandibular
      anticlockwise rotation during postoperative orthodontic treatment and compared it
      with the actual post-treatment mandibular position. RESULTS: The actual
      postoperative mandibular forward movement (2.1 mm) was significantly greater
      compared with the forward movement (1 mm) predicted preoperatively (P < .01). The
      postoperative mandibular forward movement was greater in the groups with greater
      VD increase (>1.5 mm) or greater mandibular setback (>10 mm), even though there
      was no statistically significant difference. CONCLUSIONS: These results suggest
      that additional postoperative relapse may occur with mandibular rotational
      relapse, and VD increase and the amount of mandibular setback may affect post
      treatment mandibular position in surgery-first orthodontic treatment.

PMID- 27717710
TI  - Dysregulation of histone methyltransferases in breast cancer - Opportunities for
      new targeted therapies?
AB  - Histone methyltransferases (HMTs) catalyze the methylation of lysine and arginine
      residues on histone tails and non-histone targets. These important post
      translational modifications are exquisitely regulated and affect chromatin
      compaction and transcriptional programs leading to diverse biological outcomes.
      There is accumulating evidence that genetic alterations of several HMTs impinge
      on oncogenic or tumor-suppressor functions and influence both cancer initiation
      and progression. HMTs therefore represent an opportunity for therapeutic
      targeting in those patients with tumors in which HMTs are dysregulated, to
      reverse the histone marks and transcriptional programs associated with aggressive
      tumor behavior. In this review, we describe the known histone methyltransferases
      and their emerging roles in breast cancer tumorigenesis.

PMID- 27717717
TI  - Overview of guidelines on breast screening: Why recommendations differ and what
      to do about it.
AB  - Updated guidelines on breast cancer screening have been published by several
      major organisations over the past five years. Recommendations vary regarding both
      age range, screening interval, and even on whether breast screening should be
      offered at all. The variation between recommendations reflects substantial
      differences in estimates of the major benefit (breast cancer mortality reduction)
      and the major harm (overdiagnosis). Estimates vary considerably among randomised
      trials, as well as observational studies: from no benefit to large reductions,
      and from no overdiagnosis to substantial levels. The estimates vary according to
      the methodology of the randomised trials, and the design of the observational
      studies. Guideline recommendations reflect the choice of evidence informing them.
      While there are well-developed tools to deal with randomised trials in guideline
      work, these are not always used, or they may not be followed as recommended.
      Further, results of trials performed decades ago may no longer be applicable. For
      observational studies, the framework for inclusion in guidelines is not similarly
      well-developed and there are methodological concerns specific to screening
      interventions, such as small effects in absolute terms. There is a need for
      agreement on a hierarchy of observational study designs to quantify the major
      benefit and harm of cancer screening. This review provides a summary of recent
      guidelines on breast cancer screening and their major strengths and weaknesses,
      as well as a short overview of the major strengths and limitations of
      observational study designs. There is a need for agreement on a hierarchy of
      observational study designs in this field.

PMID- 27717718
TI  - Ovarian steroid withdrawal results in GABAA receptor upregulation in the
      photoperiodic neuroendocrine pathways of the turkey hen.
AB  - The mechanism(s) underlying photorefractoriness in temperate zone seasonally
      breeding birds remains undetermined. Our recent findings reveal a link between
      the upregulation of GABAA receptors (GABAARs) in the premammillary nucleus (PMM)
      and the state of photorefractoriness. Gonadal steroid levels fluctuate during the
      breeding season; increasing after gonadal recrudescence and declining sharply
      once gonadal regression begins. Here, we examined the effect of gonadal steroid
      withdrawal on the expression of GABAARs in the turkey PMM. Exogenous ovarian
      steroids were administered and then withdrawn from turkey hens to mimic the
      decline of ovarian steroids levels at the end of a breeding season. The
      upregulation of GABAAR alpha3, alpha4, delta, pi, and gamma2-subunits was
      observed in the PMM of the steroid withdrawal group when compared to the non
      steroid treatment group. The level of tyrosine hydroxylase, photopigment
      melanopsin, and circadian clock genes in the PMM of the steroid withdrawal group
      resembled the levels observed in the natural photorefractory hens and were
      significantly lower than those of the short-day light stimulated group. A
      reduction in gonadotropin-releasing hormone-I mRNA expressed within the nucleus
      commissurae pallii was also observed in hens undergoing steroid withdrawal. These
      results suggest that the natural decline in circulating ovarian steroid levels
      may modulate the GABAergic system in the PMM through the upregulation of GABAA
      receptors. This, in turn, could diminish the reproductive neuroendocrine
      responses to light and favor a condition resembling the state of
      photorefractoriness.

PMID- 27717719
TI  - Favorable outcome of blood urea nitrogen/creatinine-based hydration therapy 3
      months after acute ischemic stroke.
AB  - BACKGROUND: Dehydration is associated with acute ischemic stroke. However, the
      relationship between hydration therapy given during acute ischemic stroke and
      clinical outcomes remains unclear. AIMS: We determined whether hydration therapy
      in patients with a blood urea nitrogen/creatinine (BUN/Cr) ratio of at least 15
      improved clinical outcome. METHODS: We conducted a nonblinded, phase II, single
      arm, prospective study of patients with acute ischemic stroke and BUN/Cr ratio of
      at least 15 with historical controls. The hydration group received intravenous
      bolus (300-500 mL) saline followed by maintenance saline infusion (40-80 mL/h for
      the first 72 hours), whereas the control group received maintenance saline
      infusion (40-60 mL/h for the first 24 hours and 0-60 mL/h for 24-72 hours after
      stroke). The study end point was the percentage of patients with a favorable
      outcome defined as modified Rankin scale score of 2 or lower at 3 months after
      stroke. RESULTS: A total of 237 patients were enrolled (hydration, n = 134;
      control, n = 103). The mean volume of saline infused within the first 72 hours
      was significantly larger (P < .001), and the rate of favorable outcome at 3
      months after stroke was significantly higher (P = .016) in the hydration group
      than in the controls. Further analysis revealed that the difference was
      significant in the lacunar stroke subtype (P = .020) but not in the nonlacunar
      subtype. CONCLUSIONS: Blood urea nitrogen/Cr ratio-based saline hydration therapy
      in patients with acute ischemic stroke significantly increased the rate of
      favorable clinical outcome with functional independence at 3 months after stroke.

PMID- 27717720
TI  - The quantitative evaluation of intracranial pressure by optic nerve sheath
      diameter/eye diameter CT measurement.
AB  - BACKGROUND: The changes of the optic nerve sheath diameter (ONSD) have been used
      to assess changes of the intracranial pressure for 20 years. The aim of this
      research was to further quantify the technique of measuring the ONSD for this
      purpose. METHODS: Retrospective study of computed tomographic (CT) data of 1766
      adult patients with intracranial hypotension (n=134) or hypertension (n=1632)
      were analyzed. The eyeball transverse diameter (ETD) and ONSD were obtained
      bilaterally, and the ONSD/ETD ratio was calculated. The ratio was used to
      calculate the normal ONSD for patients and to estimate the intracranial pressure
      of the patients before and after the onset of the pathology. Correlation analysis
      was performed with invasively measured intracranial pressure, the presence or
      absence of papilledema, sex, and age. RESULTS: In hypotension cases, the ONSD by
      CT was 3.4+/-0.7 mm (P=.03 against normative 4.4+/-0.8 mm). In cases with
      hypertension, the diameter was 6.9+/-1.3 (P=.02, with a cutoff value ?5.5 mm).
      The ONSD/ETD ratio was 0.29+/-0.04 against 0.19+/-0.02 in healthy adults (P=.01).
      CONCLUSION: The ONSD and the ONSD/ETD ratio can indicate low intracranial
      pressure, but quantification is impossible at intracranial pressure less than 13
      mm Hg. In elevated intracranial pressure, the ONSD and the ratio provide readings
      that correspond to readings in millimeters of mercury. The ONSD method,
      reinforced with additional calculations, may help to indicate a raised
      intracranial pressure, evaluate its severity quantitatively, and establish
      quantitative goals for treatment of intracranial hypertension, but the
      limitations of the method are to be taken into account.

PMID- 27717721
TI  - Emphysematous pyelonephritis in a renal allograft.

PMID- 27717722
TI  - CT interpretations in multiply injured patients: comparison of emergency
      physicians and on-call radiologists.
AB  - OBJECTIVE: In this study, emergency physicians and on-call radiologists were
      compared regarding identification of fatal injuries on computed tomographic (CT)
      scans in patients with trauma. MATERIALS AND METHODS: Multiply injured patients
      who were older than 18 years and underwent CT scanning were included in the
      study. The CT scans were interpreted by the responsible emergency physician. At
      the same time, these images were also evaluated by the on-call radiologist. Final
      evaluation was done 1 week later by a radiology instructor who knew the clinical
      follow-up of the patient. RESULTS: The study included 156 patients. The mean age
      of the patients included in the study was found to be 41.6 years. Less than half
      (33.5%) of the patients were female and 86.5% were male. A total of 482 CT scans
      were performed in the patients. Regarding brain CTs, the concordance rate for
      emergency physicians was 98%, whereas it was 94% for on-call radiologists.
      Regarding thoracic CTs, the concordance rate for emergency physicians was 91%,
      whereas was 93% for on-call radiologists. There was a perfect concordance (kappa
      value > 0.75) for on-call radiologists and emergency physicians in terms of brain
      and thoracic CTs. Regarding abdominal-pelvic CTs, the concordance rate for
      emergency physicians was 97%, whereas it was 98% for on-call radiologists.
      Moderate concordance (kappa range = 0.40-0.75) was detected for emergency
      physicians in terms of identification of liver, spleen, kidney, and intra
      abdominal/retroperitoneal hemorrhages. There was a perfect concordance (kappa
      value > 0.75) for pelvic fractures. CONCLUSION: In this study, it was shown that
      emergency physicians were successful in identifying fatal injuries on trauma CT
      images after a short-term training on interpretation of trauma CTs.

PMID- 27717723
TI  - Assessment of IgE-mediated food allergies in children with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is an inflammatory disease of the skin, which
      is characterised by a chronic relapsing course. AIM: The aim of the study was to
      assign the prevalence of clinically active food allergies among a group of
      children between 3 months and 7 years of age, with AD. METHODS: Eighty-eight
      children with AD were screened for specific IgE antibodies to food proteins. All
      patients with AD and specific IgE antibodies to food proteins were subjected to
      Oral Food Challenges (OFCs) with the relevant foods. RESULTS: Food-sensitised
      patients with moderate levels of sIgE had clinically active food allergy to milk
      (39.28%) and egg (42.34%) on the basis of positive OFCs. High IgE and
      eosinophilia had a prevalence of almost 80% and 25%, regardless of concomitant
      food sensitisation and disease severity. CONCLUSIONS: In this study, clinically
      active food allergies were recognised in 26.13% of children with AD.
      Nevertheless, no association was confirmed between food sensitisation and AD
      severity. High IgE and peripheral eosinophilia have not been found more prevalent
      among children with severe AD nor among children with food sensitisation. Infants
      and younger children with AD should be screened for an underlying food allergy,
      regardless of disease severity.

PMID- 27717724
TI  - Comparison of various classifications for patients with common variable
      immunodeficiency (CVID) using measurement of B-cell subsets.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disease,
      characterised by hypogammaglobulinaemia leading to recurrent infections and
      various complications. The aim of this study was to classify CVID patients based
      on four known classifications (Paris, Freiburg, EUROclass, and B-cell patterns)
      by measurement of B-cell subsets and to assess the relation of each
      classification with clinical manifestations. METHODS: We measured all B-cell
      subsets as both absolute count and percentage in 30 CVID patients and 30 healthy
      individuals using four-colour flow cytometry. Moreover, we evaluated antibody
      responses to pneumococcal vaccine in patients. RESULTS: A significant reduction
      in percentage of terminal B-cell subsets (total, marginal zone-like, switched
      memory, IgM-only memory, total memory B-cells and plasmablast) and absolute count
      of all B-cell subsets along with a strong increase in CD21low B-cells has been
      observed in patients. Patients with splenomegaly and hepatomegaly clustered in
      group Ia, smB+21low and group 1 based on known classifications, and significantly
      tended to have a decreased transitional and marginal zone-like B-cells count, as
      well as an increase in CD21low B-cell counts. Patients with lymphadenopathy,
      bronchiectasis and allergy had a significant decrease in absolute count of total
      memory, switched memory and total B-cells, respectively. CONCLUSION:
      Classification of patients could provide useful information to guide clinicians
      in long-term follow-up of CVID patients. Our data demonstrate that it may be more
      accurate to use absolute counts of B-cell subpopulations in CVID patients because
      absolute counts of B-cell subsets are more associated with clinical
      manifestations compared with their percentage and also four known
      classifications.

PMID- 27717725
TI  - Airway tone dysfunction among pre-schoolers with positive asthma predictive
      index: A case-control study.
AB  - OBJECTIVE: To measure lung function by impulse oscillometry (IOS) and spirometry
      in recurrent wheezer pre-schoolers according to their asthma predictive index
      (API) condition. METHODS: We performed a case-control study enrolling all pre
      schoolers with recurrent wheezing episodes (>3 episodes confirmed by physician)
      who presented at a paediatric pulmonology clinic. The population was divided
      according to stringent API criteria into positive or negative. RESULTS: In the
      nine-month period, 109 pre-schoolers were enrolled. After excluding one patient
      (due to lung function technique problems) 108 pre-schoolers (56 males, age range
      from 24 to 72 months) completed the study; 50 belong to positive API and 58 to
      negative API group. There were no differences in demographics between groups.
      More use of ICS was found in those with positive API than with negative API (62%
      vs. 12%, respectively, p=0.001). No differences in basal lung function and post
      bronchodilator response to salbutamol (by IOS or spirometry) were found between
      positive and negative API pre-schoolers. However, those positive API pre
      schoolers with ICS had significantly higher central basal airway resistance (RA
      at 20Hz) and higher post-BD response (% change in FEF25-75 and in FEV0.5) than
      those positive API without ICS. CONCLUSION: Recurrent wheezer pre-schoolers with
      positive API and ICS used may have airway dysfunction. More studies are needed to
      confirm this finding.

PMID- 27717726
TI  - Association of interleukin-1 family gene polymorphisms with juvenile idiopathic
      arthritis in Iranian population.
AB  - BACKGROUND: Cytokines, including interleukin-1 (IL-1), seem to contribute towards
      the pathogenesis of juvenile idiopathic arthritis (JIA), so this study was
      designed to evaluate the associations of IL-1 gene cluster and IL-1 receptor (IL
      1R) gene single nucleotide polymorphisms (SNPs) with JIA proneness in Iranian
      population. MATERIALS AND METHODS: Genomic DNA of 55 Iranian patients with JIA
      and 140 controls were extracted and typed for IL-1alpha gene at position -889, IL
      1beta gene at positions -511 and +3962, IL-1R gene at position Pst-I 1970, and
      interleikin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100, using
      polymerase chain reaction with sequence-specific primers method, and compared
      between patients and controls. RESULTS: The CC genotype of IL-1Ra at Mspa-I 11100
      position was found to be more frequent in patients with JIA compared to healthy
      individuals (P=0.03), although the CT genotype at the same position was
      significantly higher in the control group in comparison with patients with JIA
      (P=0.02). No significant differences were observed between the two groups of case
      and control for IL-1alpha (-889 C/T), IL-1beta (-511 C/T and +3962 C/T) and IL-1R
      (Pst-1 1970 C/T). CONCLUSION: The results of the present investigation suggest
      that certain IL-1Ra gene variants are associated with individuals' susceptibility
      to JIA. Nevertheless, further studies are required to establish the results of
      the current study.

PMID- 27717727
TI  - Efficacy of parthenolide on lung histopathology in a murine model of asthma.
AB  - BACKGROUND: Parthenolide is the active constituent of the plant 'Tanacetum
      parthenium' (Feverfew) which has been used for centuries as a folk remedy for
      inflammatory conditions. AIM OF THE STUDY: In this study we aimed to investigate
      the effects of parthenolide in a murine model of chronic asthma. MATERIALS AND
      METHODS: Thirty-five BALB/c mice were divided into five groups; I (control), II
      (placebo), III (dexamethasone), IV (parthenolide) and V (dexamethasone and
      parthenolide combination). Lung histology was evaluated after treatment with the
      study drugs. Levels of interleukin (IL)-4 and IL-5 were determined by ELISA.
      RESULTS: Histologic parameters except the number of mast and goblet cells
      improved in the parthenolide group when compared with placebo. All parameters
      except basal membrane thickness and number of mast cells were improved
      significantly better in the group receiving dexamethasone when compared with the
      parthenolide group. Improvement of most of the histologic parameters was similar
      in Groups III and V. Interleukin-4 levels were significantly reduced in the
      parthenolide group when compared to the placebo group. CONCLUSION: We
      demonstrated that parthenolide administration alleviated some of the pathological
      changes in asthma. But parthenolide alone is not efficient as dexamethasone
      therapy and the parthenolide and dexamethasone combination also did not add any
      beneficial effect to the dexamethasone treatment.

PMID- 27717728
TI  - Bergenin attenuates renal injury by reversing mitochondrial dysfunction in
      ethylene glycol induced hyperoxaluric rat model.
AB  - Bergenin, isolated from Bergenia ligulata is a potent antioxidant and
      antilithiatic agent. Present work was designed to establish the biochemical role
      of bergenin on mitochondrial dysfunction in the ethylene glycol induced
      hyperoxaluric rat model. Bergenin was administrated at a dose of 10mg/kg body wt
      i.p. from 14th day of establishing the 28 days hyperoxaluria rat model. alpha
      Tocopherol was given as positive control at a dose of 100mg/kg body wt i.p.
      Mitochondrial dysfunction was studied by evaluating the activities of respiratory
      chain complexes, mitochondrial membrane potential and reactive oxygen species.
      Histopathological analysis of the kidney tissue was done after Pizzolato
      staining. Also, expression of monocyte chemoattractant protein -1(MCP-1) and
      kidney injury marker protein (KIM-1) were studied and the levels of IL-1beta were
      evaluated in kidney tissue homogenate. Mitochondrial dysfunction during stone
      crystallization was evident by decreased activities of electron transport chain
      complexes I, II and IV and augmented mitochondrial oxidative stress in
      hyperoxaluric rats. Bergenin treatment significantly (P<0.05) restored the
      activities of these complexes. Moreover, it curtailed the lipid peroxidation and
      up regulated antioxidant levels, ameliorating the state of mitochondrial
      dysfunction. The protective role of bergenin was also reinforced by reducing IL
      1beta production and expression of KIM-1 and MCP-1 in the renal tissue. The
      findings of the present study provide evidence that bergenin exerted protective
      effects in hyperoxaluria through mitochondrial protection that involves
      attenuation of oxidative stress. Hence, it presented itself as an effective
      remedy in combating urolithiasis.

PMID- 27717729
TI  - Vasodilation and hypotension of a novel 3-benzylquinazolin- 4(3H)-one derivative
      via the inhibition of calcium flux.
AB  - A novel 3-benzylquinazolin-4(3H)-one derivative Z32, namely 6,7-dimethoxy-3-(3
      chloro-4-(4-fluorobenzyloxy)benzyl)quinazolin-4(3H)-one was synthesized. The
      vasorelaxant and antihypertensive effects of Z32 and its underlying mechanisms
      were investigated. The following methods were used. The isometric tension of
      artery ring segments was recorded using an in vitro myography system. Changes in
      the calcium influx in mesenteric arteries were surveyed using a real-time
      confocal microscopy. The arterial pressure of spontaneously hypertensive rats was
      measured in vivo using a non-invasive tail cuff blood pressure system. The
      results showed that Z32 can relax rat mesenteric arteries pre-constricted by KCl
      or phenylephrine in a concentration-dependent manner. The vasorelaxant effects
      were not affected by the removal of the endothelium, blockade of potassium
      channels by tetraethylammonium chloride, or inhibition of either guanylate
      cyclase by ODQ, nitric oxide synthase by l-NAME, or cyclooxygenase by
      indomethacin. In Ca2+-free conditions, Z32 did not affect the constriction evoked
      by caffeine, however, significantly reduced the constrictions induced (1) by
      phenylephrine, (2) by CaCl2 in either phenylephrine (in the presence of
      verapamil) or KCl stimulated arteries, (3) by extracellular Ca2+ restoration in
      thapsigargin-treated mesenteric arteries, and (4) by the activator of protein
      kinase C phorbol-12, 13-dibutyrate, and the inhibitor of protein tyrosine
      phosphatase sodium orthovanadate. Further, Z32 decreased the systolic and
      diastolic arterial pressure of spontaneously hypertensive rats in a dose
      dependent manner. In conclusion, Z32 lowers the arterial pressure and induces
      vasorelaxation through the inhibition of calcium flux, probably via a protein
      tyrosine phosphorylation-dependent way.

PMID- 27717731
TI  - Titanium oxide thin films obtained with physical and chemical vapour deposition
      methods for optical biosensing purposes.
AB  - This work discusses an application of titanium oxide (TiOx) thin films deposited
      using physical (reactive magnetron sputtering, RMS) and chemical (atomic layer
      deposition, ALD) vapour deposition methods as a functional coating for label-free
      optical biosensors. The films were applied as a coating for two types of sensors
      based on the localised surface plasmon resonance (LSPR) of gold nanoparticles
      deposited on a glass plate and on a long-period grating (LPG) induced in an
      optical fibre. Optical and structural properties of the TiOx thin films were
      investigated and discussed. It has been found that deposition method has a
      significant influence on optical properties and composition of the films, but
      negligible impact on TiOx surface silanization effectiveness. A higher content of
      oxygen with lower Ti content in the ALD films leads to the formation of layers
      with higher refractive index and slightly higher extinction coefficient than for
      the RMS TiOx. Moreover, application of the TiOx film independently on deposition
      method enables not only for tuning of the spectral response of the investigated
      biosensors, but also in case of LSPR for enhancing the ability for
      biofunctionalization, i.e., TiOx film mechanically protects the nanoparticles and
      induces change in the biofunctionalization procedure to the one typical for
      oxides. TiOx coated LSPR and LPG sensors with refractive index sensitivity of
      close to 30 and 3400nm/RIU, respectively, were investigated. The ability for
      molecular recognition was evaluated with the well-known complex formation between
      avidin and biotin as a model system. The shift in resonance wavelength reached 3
      and 13.2nm in case of LSPR and LPG sensors, respectively. Any modification in
      TiOx properties resulting from the biofunctionalization process can be also
      clearly detected.

PMID- 27717730
TI  - L-Arginine supplementation improves insulin sensitivity and beta cell function in
      the offspring of diabetic rats through AKT and PDX-1 activation.
AB  - Maternal hyperglycemia can result in defects in glucose metabolism and pancreatic
      beta-cell function in offspring. The purpose of this study was to evaluate the
      impact of maternal diabetes mellitus on pancreatic islets, muscle and adipose
      tissue of the offspring, with or without oral l-Arginine supplementation. The
      induction of diabetes was performed using streptozotocin (60mg/kg). Animals were
      studied at 3 months of age and treatment (sucrose or l-Arginine) was administered
      from weaning. We observed that l-Arg improved insulin sensitivity in the
      offspring of diabetic mothers (DA), reflected by higher insulin-induced
      phosphorylation of Akt in muscle and adipose tissue. Insulin resistance is
      associated with increased oxidative stress and the NADPH oxidase enzyme plays an
      important role. Our results showed that the augmented interaction of p47PHOX with
      gp91PHOX subunits of the enzyme in skeletal muscle tissue in the offspring of
      diabetic rats (DV) was abolished after l-Arg treatment in DA rats. Maternal
      diabetes caused alterations in the islet functionality of the offspring leading
      to increased insulin secretion at both low (2.8mM) and high (16.7mM)
      concentrations of glucose. l-Arg reverses this effect, suggesting that it may be
      an important modulator in the insulin secretory process. In addition it is
      possible that l-Arg exerts its effects directly onto essential molecules for the
      maintenance and survival of pancreatic islets, decreasing protein expression of
      p47PHOX while increasing Akt phosphorylation and PDX-1 expression. The mechanism
      by which l-Arg exerts its beneficial effects may involve nitric oxide
      bioavailability since treatment restored NO levels in the pancreas.

PMID- 27717732
TI  - Evidence that the endometrial microbiota has an effect on implantation success or
      failure.
AB  - BACKGROUND: Bacterial cells in the human body account for 1-3% of total body
      weight and are at least equal in number to human cells. Recent research has
      focused on understanding how the different bacterial communities in the body (eg,
      gut, respiratory, skin, and vaginal microbiomes) predispose to health and
      disease. The microbiota of the reproductive tract has been inferred from the
      vaginal bacterial communities, and the uterus has been classically considered a
      sterile cavity. However, while the vaginal microbiota has been investigated in
      depth, there is a paucity of consistent data regarding the existence of an
      endometrial microbiota and its possible impact in reproductive function.
      OBJECTIVE: This study sought to test the existence of an endometrial microbiota
      that differs from that in the vagina, assess its hormonal regulation, and analyze
      the impact of the endometrial microbial community on reproductive outcome in
      infertile patients undergoing in vitro fertilization. STUDY DESIGN: To identify
      the existence of an endometrial microbiota, paired samples of endometrial fluid
      and vaginal aspirates were obtained simultaneously from 13 fertile women in
      prereceptive and receptive phases within the same menstrual cycle (total samples
      analyzed n = 52). To investigate the hormonal regulation of the endometrial
      microbiota during the acquisition of endometrial receptivity, endometrial fluid
      was collected at prereceptive and receptive phases within the same cycle from 22
      fertile women (n = 44). Finally, the reproductive impact of an altered
      endometrial microbiota in endometrial fluid was assessed by implantation, ongoing
      pregnancy, and live birth rates in 35 infertile patients undergoing in vitro
      fertilization (total samples n = 41) with a receptive endometrium diagnosed using
      the endometrial receptivity array. Genomic DNA was obtained either from
      endometrial fluid or vaginal aspirate and sequenced by 454 pyrosequencing of the
      V3-V5 region of the 16S ribosomal RNA (rRNA) gene; the resulting sequences were
      taxonomically assigned using QIIME. Data analysis was performed using R packages.
      The chi2 test, Student t test, and analysis of variance were used for statistical
      analyses. RESULTS: When bacterial communities from paired endometrial fluid and
      vaginal aspirate samples within the same subjects were interrogated, different
      bacterial communities were detected between the uterine cavity and the vagina of
      some subjects. Based on its composition, the microbiota in the endometrial fluid,
      comprising up to 191 operational taxonomic units, was defined as a Lactobacillus
      dominated microbiota (>90% Lactobacillus spp.) or a non-Lactobacillus-dominated
      microbiota (<90% Lactobacillus spp. with >10% of other bacteria). Although the
      endometrial microbiota was not hormonally regulated during the acquisition of
      endometrial receptivity, the presence of a non-Lactobacillus-dominated microbiota
      in a receptive endometrium was associated with significant decreases in
      implantation [60.7% vs 23.1% (P = .02)], pregnancy [70.6% vs 33.3% (P = .03)],
      ongoing pregnancy [58.8% vs 13.3% (P = .02)], and live birth [58.8% vs 6.7% (P =
      .002)] rates. CONCLUSION: Our results demonstrate the existence of an endometrial
      microbiota that is highly stable during the acquisition of endometrial
      receptivity. However, pathological modification of its profile is associated with
      poor reproductive outcomes for in vitro fertilization patients. This finding adds
      a novel microbiological dimension to the reproductive process.

PMID- 27717734
TI  - [Continent cutaneous urinary diversion after cystectomy for cancer: A reliable
      alternative? A monocentric retrospective study].
AB  - INTRODUCTION: Among available urinary diversion, continent cutaneous urinary
      diversion (CCUD) is not frequently used after cystectomy for malignancy. The aim
      of our work was to assess mid-term oncological and functional outcomes of CCUD in
      case of malignancies. PATIENTS AND METHODS: We retrospectively included all
      patients who underwent CCUD after radical cystectomy for cancer (according
      Mitrofanoff or Monti's principle) between July 2001 and November 2015 in our
      department. Perioperative data, oncological and functional outcomes were
      reported. To measure disease specific quality of life, we used the French version
      of Bladder Cancer Index. RESULTS: Overall 12 patients were involved in the study.
      With a median follow-up of 32 months, we noticed one death due to cancer
      recurrence. Early postoperative complications occurred in 8 patients, with one
      requiring reoperation. The late postoperative complication rate was 66%, whose 4
      patients (33%) presented cutaneous stenosis. Overall satisfaction rate was scored
      8.9/10 and body image was preserved for 75% of patients. At last follow-up,
      continence (no urinary leakage) was achieved for 62.5% of patient. Sexual
      impairment was significant for 5 patients. CONCLUSION: The CCUD is a valid
      alternative to other urinary diversions with similar oncological results and with
      a similar rate of complications. The high satisfaction rate was related to the
      preservation of body image and the high rate of continence. LEVEL OF EVIDENCE: 5.

PMID- 27717733
TI  - Novel mechanisms and approaches to overcome multidrug resistance in the treatment
      of ovarian cancer.
AB  - Ovarian cancer remains the leading cause of gynecological cancer-related
      mortality despite the advances in surgical techniques and chemotherapy drugs over
      the past three decades. Multidrug resistance (MDR) to chemotherapy is the major
      cause of treatment failure. Previous research has focused mainly on strategies to
      reverse MDR by targeting the MDR1 gene encoded P-glycoprotein (Pgp) with small
      molecular compound inhibitors. However, prior Pgp inhibitors have shown very
      limited clinical success because these agents have relatively low potency and
      high toxicity. Therefore, identification of more specific and potent new
      inhibitors would be useful. In addition, emerging evidence suggests that cancer
      stem cells (CSCs), deregulated non-coding RNA (ncRNA), autophagy, and tumor
      heterogeneity also contribute significantly to drug sensitivity/resistance in
      ovarian cancer. This review summarizes these novel mechanisms of MDR and
      evaluates several new concepts to overcome MDR in the treatment of ovarian
      cancer. These new strategies include overcoming MDR with more potent and specific
      Pgp inhibitors, targeting CSCs and ncRNA, modulating autophagy signaling pathway,
      and targeting tumor heterogeneity.

PMID- 27717735
TI  - [Application of the working time European directive on surgical residents in
      France: Threat or benefit for the training?]

PMID- 27717736
TI  - [Factors influencing the choice of nondonor families in a French organ-harvesting
      center].
AB  - OBJECTIVES: Report the reasons that lead families to refuse organ donation during
      their close solicitation by hospital coordination. MATERIAL AND METHODS: A
      retrospective study was conducted between 2012 and 2015, including 148 (34%)
      refusal of organ donation among 426 patients identified in a state of brain
      death. A questionnaire of the family was completed for each interview. Collected
      data concerned patient characteristics, cause of death, description of the
      interview and reasons for refusal. A descriptive statistical analysis was
      performed. RESULTS: The median age of patients was 50 years with a sex ratio of
      1.4 men to 1 woman. The most common reason for non-donor family was the desire to
      maintain the integrity of the body of the patient (28%) followed by a religious
      order pattern (11%), brutality and suddenness of death (9%), the denial of death
      (6%) and early age of the donor (5%). In 39% of cases, the family said that the
      donor had expressed a written or oral refusal in his lifetime. CONCLUSION: A
      better understanding of the reasons leading to the refusal of non-donor family
      could provide assistance to the medical team on actions to general public with
      the aim to reduce the refusal rate. LEVEL OF EVIDENCE: 4.

PMID- 27717737
TI  - [Hospitalization rate in relation to severe complications of transrectal prostate
      biopsy: About 2715 patients biopsied].
AB  - MAIN OBJECTIVE: To identify hospitalizations directly related to a complication
      occurring within 30 days following a transrectal prostate biopsy (PBP). SECONDARY
      OBJECTIVES: Overall hospitalization rates, mortality rates, potential
      predisposing factors for complications. PATIENTS AND METHODS: Single-center study
      including all patients who underwent PBP between January 2005 and January 2012.
      Any hospitalization occurring within 30 days of the PBP for urgent motive was
      considered potentially attributable to biopsy. We identified the reason for
      hospitalization with direct complications (urinary infection or fever, rectal
      bleeding, bladder caillotage, retention) and indirect (underlying comorbidities
      decompensation) of the biopsy. The contributing factors were anticoagulant or
      antiplatelet treatment well as waning immunity factors (corticosteroid therapy,
      HIV, chemotherapy or immunodulateur). RESULTS: Among 2715 men who underwent PBP,
      there were 120 (4.4%) hospitalizations including 28 (1.03%) caused by the biopsy.
      Twenty-five (0.92%) were related to a direct complication of biopsy: 14 (56%) for
      urinary tract infection or fever including 1 hospitalization in intensive care, 5
      (20%) for rectal bleeding which required several transfusions 1, 10 (40%) urinary
      retention and 3 (0.11%) for an indirect complication (2 coronary syndromes and 1
      respiratory failure). Several direct complications were associated in 3 cases.
      Only two hospitalizations associated with rectal bleeding were taking an
      antiplatelet or anticoagulant. There was no association between hospitalization
      for urinary tract infections and a decreased immune status. The first death
      observed in our study occurred at D31 of pulmonary embolism (advanced metastatic
      patient with bladder cancer). Twenty (60.6%) patients urgently hospitalized did
      not have prostate cancer. CONCLUSIONS: Within this large sample of patients the
      overall rate of hospitalization due to the realization of a PBP was 1%. It has
      not been found predictive of complications leading to hospitalization. LEVEL OF
      EVIDENCE: 4.

PMID- 27717738
TI  - Influence of Relative Strength on Functional Independence of Patients With Spinal
      Cord Injury.
AB  - OBJECTIVE: To investigate the influence of strength values and fat mass on
      functional independence of men with different spinal cord injury (SCI) levels.
      DESIGN: Cross-sectional study. SETTING: Hospital network. PARTICIPANTS: Men with
      SCI (N=45). INTERVENTIONS: Subjects were assessed in functional independence
      scales, a 1 repetition maximum (1RM) test, and body composition to detect
      absolute and relative strength: 1RM divided by body mass (BM) and lean body mass
      (LBM), respectively. MAIN OUTCOME MEASURES: Stepwise multiple regression analysis
      was used to verify the influence of predictors on functional independence (FIM
      and Spinal Cord Independence Measure [SCIM] scale and subscales). Receiver
      operating characteristic curves were created to identify cutoff points of
      strength for functional independence. RESULTS: The best models for FIM total, FIM
      mobility, and SCIM total used 1RM as the best predictor (adjusted R2=.75, .67,
      and .65, respectively; P<.05). Relative strength (1RM/LBM) was the best predictor
      for SCIM mobility (adjusted R2=.62, P<.05). A FIM score of 69 has a 1RM cutoff
      point of 50.1kg, and a FIM score of 76 has cutoff points of .73 for 1RM/BM and
      .91 for 1RM/LBM. A SCIM score of 68 has cutoff points for 1RM, 1RM/BM, and
      1RM/LBM of 50.1kg, .77, and .92, respectively. CONCLUSIONS: Cutoff points of
      relative strength should be used as determinant variables for independence,
      health, or sports performance. This study may contribute to more adequate
      guidance of physical activity during a rehabilitation program and after
      discharge.

PMID- 27717739
TI  - How Myosin Generates Force on Actin Filaments.
AB  - How myosin interacts with actin to generate force is a subject of considerable
      controversy. The major debate centers on understanding at what point in force
      generation the inorganic phosphate is released with respect to the lever arm
      swing, or powerstroke. Resolving the controversy is essential for understanding
      how force is produced as well as the mechanisms underlying disease-causing
      mutations in myosin. Recent structural insights into the powerstroke have come
      from a high-resolution structure of myosin in a previously unseen state and from
      an electron cryomicroscopy (cryo-EM) 3D reconstruction of the actin-myosin-MgADP
      complex. Here, we argue that seemingly contradictory data from time-resolved
      fluorescence resonance energy transfer (FRET) studies can be reconciled, and we
      put forward a model for myosin force generation on actin.

PMID- 27717741
TI  - Comparison of three commercial dosimetric systems in detecting clinically
      significant VMAT delivery errors.
AB  - AIM: To study the sensitivity of three commercial dosimetric systems, Delta4,
      Multicube and Octavius4D, in detecting Volumetric Modulated Arc Therapy (VMAT)
      delivery errors. METHODS: Fourteen prostate and head and neck (H&N) VMAT plans
      were considered for this study. Three types of errors were introduced into the
      original plans: gantry angle independent and dependent MLC errors, and gantry
      angle dependent dose errors. The dose matrix measured by each detector system for
      the no-error and error introduced delivery were compared with the reference
      Treatment Planning System (TPS) calculated dose matrix for no-error plans using
      gamma (gamma) analysis with 2%/2mm tolerance criteria. The ability of the
      detector system in identifying the minimum error in each scenario was assessed by
      analysing the gamma pass rates of no error delivery and error delivery using a
      Wilcoxon signed-rank test. The relative sensitivity of the system was assessed by
      determining the slope of the gamma pass line for studied error magnitude in each
      error scenario. RESULTS: In the gantry angle independent and dependent MLC error
      scenario the Delta4, Multicube and Octavius4D systems detected a minimum 2mm
      error. In the gantry angle dependent dose error scenario all studied systems
      detected a minimum 3% and 2% error in prostate and H&N plans respectively. In the
      studied detector systems Multicube showed relatively less sensitivity to the
      errors in the majority of error scenarios. CONCLUSION: The studied systems
      identified the same magnitude of minimum errors in all considered error
      scenarios.

PMID- 27717740
TI  - Antimicrobial growth promoter use in livestock: a requirement to understand their
      modes of action to develop effective alternatives.
AB  - Antimicrobial agents (AMAs) have been used in agriculture since the 1950s as
      growth-promoting agents [antimicrobial growth promoters (AGPs)]. They have
      provided benefits to the agricultural industry by increasing production
      efficiencies and maximising livestock health, yet the potential risks surrounding
      resistance to AMAs in medically important pathogenic bacteria have enhanced
      public and government scrutiny regarding AMA use in agriculture. Although it is
      recognised that AGP administration can select for resistance to AMAs in enteric
      bacteria of livestock, conclusive evidence showing a link between resistant
      bacteria from livestock and human health is lacking (e.g. transmission of
      resistant zoonotic pathogens). Livestock production output must be increased
      significantly due to the increase in global population, and thus the
      identification of non-AMA alternatives to AGP use is required. One strategy
      employed to identify alternatives to AGPs is an observational empirical
      methodology, but this approach has failed to deliver effective alternatives. A
      second approach is aimed at understanding the mechanisms involved in AGP function
      and developing alternatives that mimic the physiological responses to AGPs. New
      evidence indicates that AGP function is more complex than merely affecting
      enteric bacterial populations, and AGPs likely function by directly or indirectly
      modulating host responses such as the immune system. As such, a more
      comprehensive understanding of the mechanisms associated with AMA function as
      AGPs will facilitate the development of effective alternatives.

PMID- 27717742
TI  - Effect of intraocular pressure (IOP) and choroidal circulation on controlled
      episcleral drug delivery to retina/vitreous.
AB  - Transscleral drug delivery may become a safe alternative to the intravitreal
      injection for chronic retinal diseases such as age-related macular degeneration
      or diabetic macular edema. However, the drug delivered onto the sclera subjects
      to vigorous clearance by episcleral and choroidal circulation; in addition, the
      penetration from episclera to retina needs to overcome counter-directional ocular
      fluid current driven by intraocular pressure (IOP) as well as unfavorable drug
      disposition exerted by drug transporters before the drug reach retina. It is
      imperative to understand these processes and quantitate their influence for
      efficient designing of a sustained formulation or device to achieve efficient
      transscleral drug delivery. The current study was focused on the effects of
      intraocular pressure (IOP) and choroidal circulation on transscleral drug
      delivery using triamcinolone acetonide (TA) as a model drug. Rabbit eye IOP was
      modulated through cannulation in ex vivo study or through cryopexy of ciliary
      body in vivo studies before subtenon TA injection or episcleral TA-film
      implantation. In a subgroup of the rabbit eyes, localized choroid atrophy was
      induced by cryopexy before TA-film implantation. Each condition had a concurrent
      control group. The vitreous TA concentration was quantitated by ultra-performance
      liquid chromatography coupled with tandem mass spectrometry (UPLC/MS/MS). The
      vitreous TA concentration was compared between the study and control groups for
      effect of IOP or choroid circulation. For ex vivo studies, higher IOP was a
      significant effect against TA penetration from episclera towards vitreous. TA was
      8.5+/-5ng/mL in receptor chamber with a cross pressure of 50mmHg versus 15.9+/
      10ng/mL with the cross pressure of 5mmHg; p=0.001, t-test. A multivariate
      regression demonstrated each mmHg of IOP increase would result in 3ng/mL lower
      concentration in the receptor chamber. Similar IOP effect was also identified in
      a 3-hour study using euthanized rabbit eyes whose IOP was controlled at 10 or
      40mmHg by cannulation (3261+/-1821ng/mL vs. 755+/-763ng/mL; p=0.013, Wilcoxon
      test). However, the effect of IOP was not significant in alive animal with the
      same IOP setting. In vivo chronic study using low IOP (7.7mmHg) versus normal IOP
      (14.4mmHg), vitreous TA was not statistically significant (154+/-200ng/mL vs.
      80+/-130ng/mL, p=0.17, Wilcoxon test). However, removing of choroidal circulation
      by local cryopexy significantly enhanced the TA penetration from episclera to
      vitreous (mean 163+/-129.8ng/mL for choroidal cryopexy vs. 81.8+/-37.2ng/mL for
      ciliary cryopexy or 75.5+/-36ng/mL for control group, p=0.007, regression
      analysis). In conclusion, the effect of IOP on transscleral drug delivery was not
      a significant effect in alive rabbit eyes; however, choroidal circulation seems
      to be a significant effect to affect TA penetration from episclera towards retina
      and vitreous.

PMID- 27717744
TI  - Sex steroids effects on guinea pig airway smooth muscle tone and intracellular
      Ca2+ basal levels.
AB  - : Testosterone (TES), other androgens and female sex steroids induce non-genomic
      rapid relaxing effects in airway smooth muscle (ASM). In guinea pig ASM, basal
      tension was relaxed by dehydroepiandrosterone (DHEA) and TES; 17beta-estradiol
      (E2) had a small effect. Blockers of L-type voltage dependent Ca2+ channel (L
      VDCC, D-600) and store operated Ca2+ channel (SOC, 2-APB) also relaxed the basal
      tone. In tracheal myocytes, DHEA and TES diminished intracellular basal Ca2+
      concentrations (b[Ca2+]i) as D-600+2-APB but to a higher extend. TES after D
      600+2APB or Pyr3, a blocker of canonical transient receptor potential 3 (TRPC3),
      further decreased b[Ca2+]i rendering this response equal to TES alone. With
      indomethacin, the b[Ca2+]i decrease induced by the blockade of L-VDCC and TRPC3
      was not changed by the addition of TES. PGE2 or forskolin addition after D600+2
      APB, decreased b[Ca2+]i resembling TES response. An adenylate cyclase inhibitor
      followed by D-600+2-APB lowered b[Ca2+]i, TES showed no further effect. Carbachol
      induced [Ca2+]i increment was reduced by TES or DHEA. 17beta-estradiol diminished
      KCl-induced contraction and, in tracheal myocytes, the voltage-dependent inward
      Ca2+ current. CONCLUSION: DHEA and TES diminish ASM tone and b[Ca2+]i by blocking
      L-VDCC and probably a constitutively active TRPC3, and by PGE2 synthesis. E2
      lowers ASM basal tone by blocking only L-VDCC.

PMID- 27717743
TI  - AKT1 has dual actions on the glucocorticoid receptor by cooperating with 14-3-3.
AB  - Glucocorticoids are important therapeutic compounds for acute lymphoblastic
      leukemia (ALL). AKT1 or the protein kinase B is frequently activated in ALL, and
      contributes to the development of glucocorticoid resistance. We examined impact
      of AKT1 on glucocorticoid receptor (GR)-induced transcriptional activity in
      cooperation with phospho-serine/threonine-binding protein 14-3-3. AKT1 has two
      distinct actions on GR transcriptional activity, one through segregation of GR in
      the cytoplasm by phosphorylating GR at Ser-134 and subsequent association of 14-3
      3, and the other through direct modulation of GR transcriptional activity in the
      nucleus. For the latter, AKT1 and 14-3-3 are attracted to DNA-bound GR,
      accompanied by AKT1-dependent p300 phosphorylation, H3S10 phosphorylation and
      H3K14 acetylation at the DNA site. These two actions of AKT1 regulate distinct
      sets of glucocorticoid-responsive genes. Our results suggest that specific
      inhibition of the AKT1/14-3-3 activity on the cytoplasmic retention of GR may be
      a promising target for treating glucocorticoid resistance observed in ALL.

PMID- 27717746
TI  - Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1
      cooperates with glycogen synthase kinase-3beta to regulate osteogenesis of bone
      marrow mesenchymal stem cells in type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is associated with inhibited osteogenesis of bone
      marrow mesenchymal stem cells (BMSCs). Brain and muscle ARNT-like protein 1
      (BMAL1) has been linked to the T2DM-related bone remodeling, however, the
      specific mechanism is still unclear. Herein, we aimed to determine the role of
      BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Inhibited osteogenesis
      and BMAL1 expression were showed in diabetic BMSCs. And while beta-catenin and T
      cell factor (TCF) expression were decreased, the glycogen synthase kinase-3beta
      (GSK-3beta) and nemo-like kinase (NLK) expression were increased in diabetic
      BMSCs. Moreover, over-expression of BMAL1 led to recovered osteogenesis ability
      and activation of Wnt/beta-catenin pathway, which was partially due to inhibition
      of GSK-3beta caused by over-expression of BMAL1. Taken together, our findings
      provide new insights into the role of BMAL1 in T2DM-induced suppression of BMSCs
      osteogenesis. Over-expressed BMAL1 could recover BMSCs osteogenesis in T2DM
      partially by decreasing GSK-3beta expression to activate Wnt/beta-catenin
      pathway. BMAL1 may have a potential use in repairing diabetic bone metabolic
      disorders.

PMID- 27717745
TI  - Environmental estrogen-like endocrine disrupting chemicals and breast cancer.
AB  - BACKGROUND: Estrogen-mimicking endocrine disruptors (EEDs) such as
      polychlorinated biphenyls (PCBs), bisphenol A (BPA), and phthalates have been
      found ubiquitously throughout our environment. Although exposure to EEDs has the
      ability to interfere with endocrine control of reproductive function and
      development in both humans and wildlife, inconsistent reports have made it
      difficult to draw conclusions concerning the hypothesized increased risk of
      breast cancer associated with EEDs. OBJECTIVES: The purpose of this study was to
      examine the cross-sectional relationship between exposure to PCBs, BPA or
      phthalates; and risk of breast cancer in U.S. women using the Centers for Disease
      Control and Prevention's National Health and Nutrition Examination Survey
      (NHANES) data between 1999 and 2004. METHODS: We analyzed data from female
      participants (20 years of age and older) collected by NHANES between 1999 and
      2004 for exposure assessment based on lipid adjusted serum levels of 6 individual
      PCB congeners (PCB 074, 099, 118, 138, 153, and 180), the sum of dioxin-like PCBs
      (074 and 118), and the sum of non-dioxin-like PCBs (099 + 138 + 153 + 187).
      Levels of urinary BPA and seven phthalate metabolites mono-n-butyl phthalate
      (MnBP), mono-isobutyl phthalate (MiBP), mono-ethyl phthalate (MEP), mono-(3
      caroxypropyl) phthalate (MCPP), mono-benzyl phthalate (MZP), and three
      metabolites of di (2-ehtylhexyl) phthalate (DEHP): [mono-2-ethylhexyl phthalate
      (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5
      oxohexyl) phthalate (MEOHP)] were obtained from the 2003-2010 yearly survey
      cycles in participants aged 6 years and older. Assessments of EEDs or their
      metabolites were analyzed in conjunction with medical and reproductive health
      questionnaire data. Age, race/ethnicity, age at menarche, body mass index (BMI;
      kg/m2), and lactation were considered as potential confounders in our final
      models. Geometric means (GM) were calculated to compare PCB, BPA or phthalate
      concentrations in women who self-reported a breast cancer diagnosis versus women
      who self-reported never being diagnosed with breast cancer. Logistic regression
      models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI)
      for the association between PCB, BPA or phthalate measurements and breast cancer.
      RESULTS: In age, race/ethnicity, and BMI adjusted models, PCB138 was the only
      congener found to be significantly associated with breast cancer [OR of 3.16; 95%
      CI: 1.14-8.76]. We also found the sum of non-dioxin-like PCBs to be significantly
      associated with breast cancer [OR of 1.14; 95% CI: 1.00-1.29]. Risk of breast
      cancer, however, was not found to be significantly associated with phthalate,
      phthalate metabolites, and BPA in unadjusted or adjusted logistic regression
      models. CONCLUSIONS: Our results suggest a link between environmental exposures
      to PCB 138 and breast cancer. There were no significant associations between
      phthalates or BPA and breast cancers. These findings should be interpreted with
      caution because of the use of cross-sectional self-reported data and a small
      sample size of breast cancer subjects. Nonetheless, our finding emphasizes a need
      of comprehensive environmental molecular epidemiologic study to determine the
      potential role of environmental exposures to PCBs, phthalates, and BPA in the
      development of breast cancer.

PMID- 27717747
TI  - Lack of stability at more than 12 months of follow-up after anterior cruciate
      ligament reconstruction using all-inside quadruple-stranded semitendinosus graft
      with adjustable cortical button fixation in both femoral and tibial sides.
AB  - INTRODUCTION: The use of the semitendinosus tendon alone for anterior cruciate
      ligament reconstruction keeps the gracilis muscle intact and decreases anterior
      pain in comparison with the use of the patellar tendon. Recently, Lubowitz
      described a new all-inside technique with an ST4 tendon fixed with a cortical
      button in both femoral and tibial sides. We hypothesized that this type of graft
      with cortical button fixation provides well-controlled residual anterior tibial
      translation (<3mm). The aim of this study was to assess the results obtained with
      this technique in terms of laxity and IKDC score at more than 1 year of follow
      up. MATERIAL AND METHODS: We performed a prospective single-center study to
      evaluate the results with this procedure with at least 1 year of follow-up. The
      primary endpoint was the objective IKDC score and side-to-side anterior tibial
      translation difference. The secondary endpoint was the subjective assessment
      using the subjective IKDC and Lysholm scores. Tunnel positioning was assessed
      using the Aglietti criteria. RESULTS: Thirty-five patients were included and
      reviewed with a mean follow-up of 19.7 months. Sixty-three percent of the
      patients were male and the mean age at the procedure was 28 years. The IKDC score
      was A or B in 43% of the patients and C or D in 57%; 54% of the patients had a
      residual side-to-side anterior tibial translation difference less than 3mm and
      29% presented significant pivot shift (grade C or D). Five patients underwent
      revision surgery, including one for rupture of the ACL reconstruction. The
      meniscal status did not influence postoperative laxity and the IKDC grade.
      DISCUSSION: Our hypothesis was not verified and the postoperative stability of
      the knee was insufficient. Postoperative side-to-side anterior tibial translation
      difference remained greater than 3mm for 16 patients and the analysis seems to
      indicate that the distal cortical fixation of the graft with an adjusted loop is
      insufficient. LEVEL OF EVIDENCE: Prospective study - Level IV.

PMID- 27717748
TI  - Whole genome sequencing and phylogenetic characterization of brown bullhead
      (Ameiurus nebulosus) origin ranavirus strains from independent disease outbreaks.
AB  - Ranaviruses are emerging pathogens associated with high mortality diseases in
      fish, amphibians and reptiles. Here we describe the whole genome sequence of two
      ranavirus isolates from brown bullhead (Ameiurus nebulosus) specimens collected
      in 2012 at two different locations in Hungary during independent mass mortality
      events. The two Hungarian isolates were highly similar to each other at the
      genome sequence level (99.9% nucleotide identity) and to a European sheatfish
      (Silurus glanis) origin ranavirus (ESV, 99.7%-99.9% nucleotide identity). The
      coding potential of the genomes of both Hungarian isolates, with 136 putative
      proteins, were shared with that of the ESV. The core genes commonly used in
      phylogenetic analysis of ranaviruses were not useful to differentiate the two
      brown bullhead ESV strains. However genome-wide distribution of point mutations
      and structural variations observed mainly in the non-coding regions of the genome
      suggested that the ranavirus disease outbreaks in Hungary were caused by
      different virus strains. At this moment, due to limited whole genome sequence
      data of ESV it is unclear whether these genomic changes are useful in molecular
      epidemiological monitoring of ranavirus disease outbreaks. Therefore, complete
      genome sequencing of further isolates will be needed to identify adequate genetic
      markers, if any, and demonstrate their utility in disease control and prevention.

PMID- 27717749
TI  - Effect of self and dual-curing on degree of conversion and crosslink density of
      dual-cure core build-up materials.
AB  - PURPOSE: Dual-cure core build-up resins have been developed to take advantages of
      both self and light-cured resin. The aim of present study was to determine the
      polymerization characteristics of self and dual-cured modes of dual-cure core
      build-up composites evaluating degree of conversion (DC) and crosslink density by
      measurement of glass-transition temperature (Tg) and hardness decrease in
      ethanol. METHODS: Clearfil Dc Core Automix (CLF) and Grandio Core Dc (GR) core
      build-up resins were selected. Twelve specimens for both composites were
      polymerized using quartz-halogen-tungsten light curing unit (QTH) and 12
      specimens polymerized chemically. DC was determined by ATR-FTIR spectroscopy.
      TG/DTA analysis was performed to determine Tg. Microhardness value of specimens
      was determined by Vickers-tester before and after specimens stored in absolute
      ethanol for 24h. RESULTS: One-way ANOVA showed no different DC values between
      dual and self-cured mode of GR and dual-cured CLF composites had higher DC than
      self-cured mode. Tg and percentage of softening in ethanol values of GR and CLF
      revealed significant difference between self and dual-cured mode. CONCLUSIONS: In
      comparison of GR and CLF, DC showed no statistical difference in both curing
      modes. However, dual and self-cured GR has statistically higher Tg values and
      lower percentage of softening in ethanol than CLF. Polymerization characteristics
      of dual-cure core build-up composites have superiority in dual-cured mode than
      self-cured.

PMID- 27717750
TI  - RISK pathway is involved in oxytocin postconditioning in isolated rat heart.
AB  - The reperfusion injury salvage kinase (RISK) pathway is a fundamental signal
      transduction cascade in the cardioprotective mechanism of ischemic
      postconditioning. In the present study, we examined the cardioprotective role of
      oxytocin as a postconditioning agent via activation of the RISK pathway (PI3K/Akt
      and ERK1/2). Animals were randomly divided into 6 groups. The hearts were
      subjected under 30minutes (min) ischemia and 100min reperfusion. OT was perfused
      15min at the early phase of reperfusion. RISK pathway inhibitors (Wortmannin; an
      Akt inhibitor, PD98059; an ERK1/2 inhibitor) and Atosiban (an OT receptor
      antagonist) were applied either alone 10min before the onset of the ischemia or
      in the combination with OT during early reperfusion phase. Myocardial infarct
      size, hemodynamic factors, ventricular arrhythmia, coronary flow and cardiac
      biochemical marker were measured at the end of reperfusion. OT postconditioning
      (OTpost), significantly decreased the infarct size, arrhythmia score, incidence
      of ventricular fibrillation, Lactate dehydrogenase and it increased coronary
      flow. The cardioprotective effect of OTpos was abrogated by PI3K/Akt, ERK1/2
      inhibitors and Atosiban. Our data have shown that OTpost can activate RISK
      pathway mostly via the PI3K/Akt and ERK1/2 signaling cascades during the early
      phase of reperfusion.

PMID- 27717751
TI  - Chemical quality and regulatory compliance of drinking water in Iceland.
AB  - Assuring sufficient quality of drinking water is of great importance for public
      wellbeing and prosperity. Nations have developed regulatory system with the aim
      of providing drinking water of sufficient quality and to minimize the risk of
      contamination of the water supply in the first place. In this study the chemical
      quality of Icelandic drinking water was evaluated by systematically analyzing
      results from audit monitoring where 53 parameters were assessed for 345 samples
      from 79 aquifers, serving 74 water supply systems. Compliance to the Icelandic
      Drinking Water Regulation (IDWR) was evaluated with regard to parametric values,
      minimum requirement of sampling, and limit of detection. Water quality compliance
      was divided according to health-related chemicals and indicators, and analyzed
      according to size. Samples from few individual locations were benchmarked against
      natural background levels (NBLs) in order to identify potential pollution
      sources. The results show that drinking compliance was 99.97% in health-related
      chemicals and 99.44% in indicator parameters indicating that Icelandic
      groundwater abstracted for drinking water supply is generally of high quality
      with no expected health risks. In 10 water supply systems, of the 74 tested,
      there was an indication of anthropogenic chemical pollution, either at the source
      or in the network, and in another 6 water supplies there was a need to improve
      the water intake to prevent surface water intrusion. Benchmarking against the
      NBLs proved to be useful in tracing potential pollution sources, providing a
      useful tool for identifying pollution at an early stage.

PMID- 27717752
TI  - Appendiceal involvement in a patient with Gaucher disease.
AB  - Almost any anatomical compartment may be involved in Gaucher disease (GD).
      Abdominal lymphadenopathy occurred during enzyme replacement therapy in more than
      a dozen children with GD so far. A fourteen-year-old boy from Serbia developed
      clinical signs of acute appendicitis six years after the onset of GD type 3
      related abdominal lymphadenopathy. Ultrasound examination showed diffuse
      thickening of the intestinal wall in the ileocoecal region with periappendicular
      infiltration. An appendectomy was performed four months after conservative
      treatment with antibiotics. Histopathology revealed macrophages with cytological
      characteristics of Gaucher cells densely crammed in mesoappendiceal adipose
      tissue. Also the multifocal replacement of subserosal tissue by Gaucher cells and
      their infiltration to a variable depth of muscularis propria of the appendix were
      verified. Frank infiltration of the vermiform appendix with Gaucher cells
      represents a novel observation in a wide spectrum of manifestations reported in
      GD. A possible causative relationship of this infiltration with appendicitis is
      considered.

PMID- 27717753
TI  - Clinical and prognostic correlates of pulmonary congestion in coronary computed
      tomography angiography data sets.
AB  - BACKGROUND: Signs of pulmonary congestion obtained from cardiac computed
      tomography angiographic (coronary CTA) images have not previously been related to
      clinical congestion or outcome and the clinical value is, therefore, unknown. Our
      objective was to test the hypothesis that signs of pulmonary congestion predict
      clinical heart failure and adverse outcome in patients with myocardial
      infarction. METHODS: Coronary CTA was performed before invasive treatment in 400
      prospectively included patients with non ST segment elevation myocardial
      infarction in an observational study. Using a previously described chest computed
      tomography evaluation algorithm, patients were classified as having "no
      congestion", "mild to moderate congestion" or "severe congestion". RESULTS: Using
      multivariate analyses, presence of pulmonary congestion on coronary CTA images
      was associated with age, female gender, left ventricular ejection fraction (LVEF)
      and left atrial size. The diagnostic accuracy for predicting clinical heart
      failure, defined as Killip class >1, was: sensitivity: 83%, specificity: 69%,
      positive predictive value: 25%, and negative predictive value: 97%. The median
      follow-up time was 50 months and the study end-point of death or hospitalization
      due to heart failure was reached in 68 (16%) patients. In a Cox proportional
      hazards model with adjustments for known risk factors and Killip class, the
      presence of "mild to moderate congestion" and "severe congestion" was
      independently associated with adverse outcome (Hazard ratio: 2.6 (95% CI:1.3-5.0)
      and 3.2 (1.3-7.5)). CONCLUSION: Signs of pulmonary congestion on coronary CTA
      images are closely correlated to cardiac dysfunction, predict clinical heart
      failure, and provide prognostic value independent of LVEF and Killip class.

PMID- 27717754
TI  - A new method for assessing the accuracy of full arch impressions in patients.
AB  - OBJECTIVE: To evaluate a new method of measuring the real deviation (trueness) of
      full arch impressions intraorally and to investigate the trueness of digital full
      arch impressions in comparison to a conventional impression procedure in clinical
      use. METHODS: Four metal spheres were fixed with composite using a metal
      application aid to the lower teeth of 50 test subjects as reference structures.
      One conventional impression (Impregum Penta Soft) with subsequent type-IV gypsum
      model casting (CI) and three different digital impressions were performed in the
      lower jaw of each test person with the following intraoral scanners: Sirona CEREC
      Omnicam (OC), 3M True Definition (TD), Heraeus Cara TRIOS (cT). The digital and
      conventional (gypsum) models were analyzed relative to the spheres. Linear
      distance and angle measurements between the spheres, as well as digital
      superimpositions of the spheres with the reference data set were executed.
      RESULTS: With regard to the distance measurements, CI showed the smallest
      deviations followed by intraoral scanners TD, cT and OC. A digital
      superimposition procedure yielded the same order for the outcomes: CI (15+/
      4MUm), TD (23+/-9MUm), cT (37+/-14MUm), OC (214+/-38MUm). Angle measurements
      revealed the smallest deviation for TD (0.06 degrees +/-0,07 degrees ) followed
      by CI (0.07 degrees +/-0.07 degrees ), cT (0.13 degrees +/-0.15 degrees ) and OC
      (0.28 degrees +/-0.21 degrees ). CONCLUSION: The new measuring method is suitable
      for measuring the dimensional accuracy of full arch impressions intraorally. CI
      is still significantly more accurate than full arch scans with intraoral scanners
      in clinical use. CLINICAL SIGNIFICANCE: Conventional full arch impressions with
      polyether impression materials are still more accurate than full arch digital
      impressions. Digital impression systems using powder application and active
      wavefront sampling technology achieve the most accurate results in comparison to
      other intraoral scanning systems (DRKS-ID: DRKS00009360, German Clinical Trials
      Register).

PMID- 27717755
TI  - Optical properties of pre-colored dental monolithic zirconia ceramics.
AB  - OBJECTIVES: The purposes of this study were to evaluate the optical properties of
      recently marketed pre-colored monolithic zirconia ceramics and to compare with
      those of veneered zirconia and lithium disilicate glass ceramics. METHODS:
      Various shades of pre-colored monolithic zirconia, veneered zirconia, and lithium
      disilicate glass ceramic specimens were tested (17.0*17.0*1.5mm, n=5). CIELab
      color coordinates were obtained against white, black, and grey backgrounds with a
      spectrophotometer. Color differences of the specimen pairs were calculated by
      using the CIEDE2000 (DeltaE00) formula. The translucency parameter (TP) was
      derived from DeltaE00 of the specimen against a white and a black background. X
      ray diffraction was used to determine the crystalline phases of monolithic
      zirconia specimens. Data were analyzed with 1-way ANOVA, Scheffe post hoc, and
      Pearson correlation testing (alpha=0.05). RESULTS: For different shades of the
      same ceramic brand, there were significant differences in L*, a*, b*, and TP
      values in most ceramic brands. With the same nominal shade (A2), statistically
      significant differences were observed in L*, a*, b*, and TP values among
      different ceramic brands and systems (P<0.001). The color differences between pre
      colored monolithic zirconia and veneered zirconia or lithium disilicate glass
      ceramics of the corresponding nominal shades ranged beyond the acceptability
      threshold. CONCLUSIONS: Due to the high L* values and low a* and b* values, pre
      colored monolithic zirconia ceramics can be used with additional staining to
      match neighboring restorations or natural teeth. CLINICAL SIGNIFICANCE: Due to
      their high value and low chroma, unacceptable color mismatch with adjacent
      ceramic restorations might be expected.

PMID- 27717756
TI  - Effect of toothbrushing duration and dentifrice quantity on enamel
      remineralisation: An in situ randomized clinical trial.
AB  - OBJECTIVES: The influence of toothbrushing duration and dentifrice quantity on
      fluoride efficacy against dental caries is poorly understood. This study
      investigated effects of these two oral hygiene factors on enamel remineralisation
      (measured as surface microhardness recovery [SMHR]), enamel fluoride uptake
      (EFU), and net acid resistance (NAR) post-remineralisation in a randomized
      clinical study using an in situ caries model. METHODS: Subjects (n=63) wore their
      partial dentures holding partially demineralised human enamel specimens and
      brushed twice-daily for two weeks, following each of five regimens: brushing for
      120 or 45s with 1.5g of 1150ppm F (as NaF) dentifrice; for 120 or 45s with 0.5g
      of this dentifrice; and for 120s with 1.5g of 250ppm F (NaF) dentifrice. RESULTS:
      Comparing brushing for 120s against brushing for 45s, SMHR and EFU increased by
      20.0% and 26.9% respectively when 1.5g dentifrice was used; and by 22.8% and
      19.9% respectively when 0.5g dentifrice was used. Comparing brushing with 1.5g
      against brushing with 0.5g dentifrice, SMHR and EFU increased by 35.3% and 51.3%
      respectively when brushing for 120s, and by 38.4% and 43.0% respectively when
      brushing for 45s. Increasing brushing duration and dentifrice quantity also
      increased the NAR value. The effects of these two oral hygiene factors on SMHR,
      EFU, and NAR were statistically significant (p<0.05 in all cases). CONCLUSION:
      Brushing duration and dentifrice quantity have the potential to influence the
      anti-caries effectiveness of fluoride dentifrices. Study NCT01563172 on
      ClinicalTrials.gov. CLINICAL SIGNIFICANCE: The effect of two key oral hygiene
      regimen factors - toothbrushing duration and dentifrice quantity - on fluoride's
      anticaries effectiveness is unclear. This 2-week home-use in situ
      remineralisation clinical study showed both these factors can influence fluoride
      bioactivity, and so can potentially affect fluoride's ability to protect against
      caries.

PMID- 27717757
TI  - Multiple Phlebovirus (Bunyaviridae) genetic groups detected in Rhipicephalus,
      Hyalomma and Dermacentor ticks from southern Portugal.
AB  - In the last decade, various research groups have reported a large diversity of
      new tick-borne phleboviruses, mostly prompted by the discovery of important human
      pathogens such as the Heartland and severe fever with thrombocytopenia syndrome
      viruses. Since these analyses have rarely been conducted using ticks collected
      from Southern Europe, this study was carried out so as to bring new insights into
      the diversity of phleboviruses circulating in Southern Portugal. Tick specimens
      were collected from the vegetation (questing ticks) or directly from animals
      (feeding ticks), and the majority analysed in pools using a detection strategy
      targeting the large (L) viral genomic segment. A high number of pools revealed
      the presence of phebovirus sequences, regardless of gender (male/female), origin
      (questing/feeding) or even species of the tick analysed. These sequences
      apparently formed three different groups in phylogenetic trees, and encoded L
      proteins characterized by group-specific amino acid residues. Furthermore, under
      the conditions used, these viruses failed to replicate in both Vero and DH82
      cells. The impact these viruses may have on human/animal health will be addressed
      in the future.

PMID- 27717758
TI  - Multiple resistance to acaricides in field populations of Rhipicephalus microplus
      from Rio Grande do Sul state, Southern Brazil.
AB  - Acaricide resistance is a major obstacle to the control of Rhipicephalus
      microplus. Historically, the indiscriminate use of chemical compounds has
      contributed to the selection of populations resistant to different classes of
      acaricides. Therefore, multiple acaricide resistance is an important threat to
      the chemical control of the cattle tick. To investigate the occurrence and extent
      of multiple resistance to acaricides in Southern Brazil we performed larval tests
      with cypermethrin, chlorpyriphos, amitraz, fipronil and ivermectin on 104 cattle
      tick field samples from different ranches in Rio Grande do Sul, between the years
      2013 and 2015. Adult immersion tests with a commercial formulation mixture of
      chlorpyriphos and cypermethrin were performed on 75 samples. Four levels of
      resistance were established according to the mortality of larvae: Level I:
      mortality between 82% and 95%; Level II: mortality between 57% and 82%; Level
      III: mortality between 25% and 57%; and Level IV: mortality lower than 25%.
      Resistance to cypermethrin was detected in 98.08% of the samples evaluated,
      mostly at resistance level IV. The frequency of samples resistant to amitraz,
      chlorpyriphos, ivermectin and fipronil was 76.92%, 60.58%, 60.58% and 53.85%
      respectively. Multiple resistance to three or more compounds was found in 78.85%
      of the samples. The results obtained in this study are alarming and reveal a new
      scenario for the challenge of tick control using chemicals. This is an issue of
      high importance to cattle production systems where this tick is responsible for a
      high economic impact.

PMID- 27717759
TI  - Noncystic Fibrosis Bronchiectasis: Regional Abnormalities and Response to Airway
      Clearance Therapy Using Pulmonary Functional Magnetic Resonance Imaging.
AB  - RATIONALE AND OBJECTIVES: Evidence-based treatment and management for patients
      with bronchiectasis remain challenging. There is a need for regional disease
      measurements as focal distribution of disease is common. Our objective was to
      evaluate the ability of magnetic resonance imaging (MRI) to detect regional
      ventilation impairment and response to airway clearance therapy (ACT) in patients
      with noncystic fibrosis (CF) bronchiectasis, providing a new way to objectively
      and regionally evaluate response to therapy. MATERIALS AND METHODS: Fifteen
      participants with non-CF bronchiectasis and 15 age-matched healthy volunteers
      provided written informed consent to an ethics board-approved Health Insurance
      Portability and Accountability Act-compliant protocol and underwent spirometry,
      plethysmography, computed tomography (CT), and hyperpolarized 3He MRI.
      Bronchiectasis patients also completed a Six-Minute Walk Test, the St. George's
      Respiratory questionnaire, and Patient Evaluation Questionnaire (PEQ), and
      returned for a follow-up visit after 3 weeks of daily oscillatory positive
      expiratory pressure use. CT evidence of bronchiectasis was qualitatively reported
      by lobe, and MRI ventilation defect percent (VDP) was measured for the entire
      lung and individual lobes. RESULTS: CT evidence of bronchiectasis and abnormal
      VDP (14 +/- 7%) was observed for all bronchiectasis patients and no healthy
      volunteers. There was CT evidence of bronchiectasis in all lobes for 3 patients
      and in 3 +/- 1 lobes (range = 1-4) for 12 patients. VDP in lobes with CT evidence
      of bronchiectasis (19 +/- 12%) was significantly higher than in lobes without CT
      evidence of bronchiectasis (8 +/- 5%, P = .001). For patients, VDP in lung lobes
      with (P < .0001) and without CT evidence of bronchiectasis (P = .006) was higher
      than in healthy volunteers (3 +/- 1%). For all patients, mean PEQ-ease-bringing
      up-sputum (P = .048) and PEQ-patient-global-assessment (P = .01) were
      significantly improved post-oscillatory positive expiratory pressure. An
      improvement in regional VDP greater than the minimum clinical important
      difference was observed for 8 of the 14 patients evaluated. CONCLUSIONS: There
      was CT and MRI evidence of structure-function abnormalities in patients with
      bronchiectasis; in approximately half, there was evidence of ventilation
      improvements after airway clearance therapy.

PMID- 27717760
TI  - CT Pulmonary Angiography Using Automatic Tube Current Modulation Combination with
      Different Noise Index with Iterative Reconstruction Algorithm in Different Body
      Mass Index: Image Quality and Radiation Dose.
AB  - RATIONALE AND OBJECTIVES: This study aimed to determine the appropriate body mass
      index (BMI)-dependent noise index (NI) setting in computed tomography pulmonary
      angiography (CTPA) with automatic tube current modulation with adaptive
      statistical iterative reconstruction (ASiR). MATERIALS AND METHODS: A total of
      480 patients who had a CTPA were divided into group A (18.5 kg/m2 <= BMI < 25
      kg/m2), group B (25 kg/m2 <= BMI < 30 kg/m2), and group C (BMI >= 30 kg/m2),
      according to their BMI values; each group had 160 patients. The three groups were
      further randomly divided into four subgroups: A1, A2, A3, A4; B1, B2, B3, B4; and
      C1, C2, C3, C4, with corresponding NI values of 26, 36, 40, and 46, respectively.
      All images were restructured with the ASiR algorithm, and the images with the
      lowest NI (26 Hounsfield units) in each group were used as reference standard.
      The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for the
      pulmonary artery of each group were calculated. Subjective image quality was
      evaluated using a five-score method by two independent radiologists. The CT dose
      index of volume and dose-length product were recorded and were converted to
      effective dose (ED). SNR and CNR in the group A, B, and C subgroups were compared
      to repeated measures analysis of variance, and the subjective score, Volumetric
      CT dose index of volume, dose-length product, and ED were compared to one-way
      analysis of variance. RESULTS: For groups A and B, the SNR, CNR, and subjective
      scores of the images in their subgroups showed no statistical differences (P
      >.05). The ED in subgroups A4 and B4 was significantly lower than that in
      subgroups A1 (by 33.24%) and B1 (by 34.47%) (P <.01). For group C, there was no
      significant difference in the SNR, CNR, and the subjective image scores between
      subgroups C3 and C1 (P >.05). The ED in subgroup C3 was significantly lower than
      the ED in subgroup C1 (by 47.75%) (P <.01) CONCLUSIONS: Patient BMI-dependent NI
      settings that are higher than the recommended value may be used in CTPA with
      automatic tube current modulation and ASiR to effectively reduce radiation dose
      while maintaining diagnostic image quality.

PMID- 27717761
TI  - Quantitative Prediction of Stone Fragility From Routine Dual Energy CT: Ex vivo
      proof of Feasibility.
AB  - RATIONALE AND OBJECTIVES: Previous studies have demonstrated a qualitative
      relationship between stone fragility and internal stone morphology. The goal of
      this study was to quantify morphologic features from dual-energy computed
      tomography (CT) images and assess their relationship to stone fragility.
      MATERIALS AND METHODS: Thirty-three calcified urinary stones were scanned with
      micro-CT. Next, they were placed within torso-shaped water phantoms and scanned
      with the dual-energy CT stone composition protocol in routine use at our
      institution. Mixed low- and high-energy images were used to measure volume,
      surface roughness, and 12 metrics describing internal morphology for each stone.
      The ratios of low- to high-energy CT numbers were also measured. Subsequent to
      imaging, stone fragility was measured by disintegrating each stone in a
      controlled ex vivo experiment using an ultrasonic lithotripter and recording the
      time to comminution. A multivariable linear regression model was developed to
      predict time to comminution. RESULTS: The average stone volume was 300 mm3
      (range: 134-674 mm3). The average comminution time measured ex vivo was 32
      seconds (range: 7-115 seconds). Stone volume, dual-energy CT number ratio, and
      surface roughness were found to have the best combined predictive ability to
      estimate comminution time (adjusted R2 = 0.58). The predictive ability of mixed
      dual-energy CT images, without use of the dual-energy CT number ratio, to
      estimate comminution time was slightly inferior, with an adjusted R2 of 0.54.
      CONCLUSIONS: Dual-energy CT number ratios, volume, and morphologic metrics may
      provide a method for predicting stone fragility, as measured by time to
      comminution from ultrasonic lithotripsy.

PMID- 27717762
TI  - The Safety of Cardiac and Thoracic Magnetic Resonance Imaging in Patients with
      Cardiac Implantable Electronic Devices.
AB  - RATIONALE AND OBJECTIVES: Studies reporting the safety of magnetic resonance
      imaging (MRI) in patients with a cardiac implantable electronic device (CIED)
      have mostly excluded examinations with the device in the magnet isocenter. The
      purpose of this study was to describe the safety of cardiac and thoracic spine
      MRI in patients with a CIED. MATERIALS AND METHODS: The medical records of
      patients with a CIED who underwent a cardiac or thoracic spine MRI between
      January 2011 and December 2014 were reviewed. Devices were interrogated before
      and after imaging with reprogramming to asynchronous pacing in pacemaker
      dependent patients. The clinical interpretability of the MRI and peak and average
      specific absorption rates (SARs, W/kg) achieved were determined. RESULTS: Fifty
      eight patients underwent 51 cardiac and 11 thoracic spine MRI exams. Twenty-nine
      patients had a pacemaker and 29 had an implantable cardioverter defibrillator.
      Seventeen percent (n = 10) were pacemaker dependent. Fifty-one patients (89%) had
      non-MRI-conditional devices. There were no clinically significant changes in
      atrial and ventricular sensing, impedance, and threshold measurements. There were
      no episodes of device mode changes, arrhythmias, therapies delivered, electrical
      reset, or battery depletion. One study was prematurely discontinued due to a
      patient complaint of chest pain of which the etiology was not determined. Across
      all examinations, the average peak SAR was 2.0 +/- 0.85 W/kg with an average SAR
      of 0.35 +/- 0.37 W/kg. Artifact significantly limiting the clinical
      interpretation of the study was present in 33% of cardiac MRI studies.
      CONCLUSIONS: When a comprehensive CIED magnetic resonance safety protocol is
      followed, the risk of performing 1.5-T magnetic resonance studies with the device
      in the magnet isocenter, including in patients who are pacemaker dependent, is
      low.

PMID- 27717763
TI  - Mode of Death in Octogenarians Treated With Cardiac Resynchronization Therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves morbidity and
      mortality in heart failure with reduced ejection fraction (HFrEF) and electrical
      dyssynchrony. CRT patients in clinical practice are older compared with clinical
      trials. OBJECTIVE: To investigate clinical response, reverse remodeling, outcome,
      and mode of death in octogenarians receiving CRT. METHODS: Baseline
      characteristics, change in New York Heart Association (NYHA) functional class,
      reverse ventricular remodeling, heart failure readmissions, all-cause mortality,
      and mode of death were evaluated in CRT patients with comparison between
      octogenarians and nonoctogenarians. In addition, annual mortality rates of
      octogenarians undergoing CRT were compared with age-matched control subjects from
      the general population with the use of national actuarial tables. RESULTS: A
      total of 686 patients, including 178 octogenarians (26%), were followed for 38 +/
      22 months. Octogenarians exhibited a similar change in NYHA functional class (P
      = .640), left ventricular ejection fraction increase (P = .796), and decrease in
      end-diastolic (P = .441) and end-systolic (P = .312) diameter compared with their
      younger counterparts undergoing CRT. Octogenarians had a higher all-cause
      mortality risk (P < .001), but heart failure readmission risk did not differ
      (hazard ratio 0.916, 95% confidence interval 0.638-1.313; P = .632). A higher
      proportion of noncardiac deaths was observed in octogenarians (74%) versus
      younger patients (50%; P = .022), with worsening heart failure rather than
      malignant tachyarrhythmia being the main cardiac cause of death. Compared with an
      age-matched sample from the general population, octogenarians receiving CRT had
      an equivalent annual mortality rate (log-rank test: P = .444). CONCLUSIONS:
      Octogenarians retain the ability to mount a significant symptomatic and
      ventricular remodeling response after CRT, resulting in survival similar to the
      general age-matched population.

PMID- 27717764
TI  - Aluminium sulfate exposure: A set of effects on hydrolases from brain, muscle and
      digestive tract of juvenile Nile tilapia (Oreochromis niloticus).
AB  - Aluminium is a major pollutant due to its constant disposal in aquatic
      environments through anthropogenic activities. The physiological effects of this
      metal in fish are still scarce in the literature. This study investigated the in
      vivo and in vitro effects of aluminium sulfate on the activity of enzymes from
      Nile tilapia (Oreochromis niloticus): brain acetylcholinesterase (AChE), muscle
      cholinesterases (AChE-like and BChE-like activities), pepsin, trypsin,
      chymotrypsin and amylase. Fish were in vivo exposed during 14days when the
      following experimental groups were assayed: control group (CG), exposure to
      Al2(SO4)3 at 1MUg.mL-1 (G1) and 3MUg.mL-1 (G3) (concentrations compatible with
      the use of aluminium sulfate as coagulant in water treatment). In vitro exposure
      was performed using animals of CG treatment. Both in vivo and in vitro exposure
      increased cholinesterase activity in relation to controls. The highest
      cholinesterase activity was observed for muscle BChE-like enzyme in G3. In
      contrast, the digestive enzymes showed decreased activity in both in vivo and in
      vitro exposures. The highest inhibitory effect was observed for pepsin activity.
      The inhibition of serine proteases was also quantitatively analyzed in zymograms
      using pixel optical densitometry as area under the peaks (AUP) and integrated
      density (ID). These results suggest that the inhibition of digestive enzymes in
      combination with activation of cholinesterases in O. niloticus is a set of
      biochemical effects that evidence the presence of aluminium in the aquatic
      environment. Moreover, these enzymatic alterations may support further studies on
      physiological changes in this species with implications for its neurological and
      digestive metabolisms.

PMID- 27717765
TI  - Economic evaluation of diabetes prevention: informing global health
      implementation decisions.

PMID- 27717766
TI  - Effectiveness of activity trackers with and without incentives to increase
      physical activity (TRIPPA): a randomised controlled trial.
AB  - BACKGROUND: Despite the increasing popularity of activity trackers, little
      evidence exists that they can improve health outcomes. We aimed to investigate
      whether use of activity trackers, alone or in combination with cash incentives or
      charitable donations, lead to increases in physical activity and improvements in
      health outcomes. METHODS: In this randomised controlled trial, employees from 13
      organisations in Singapore were randomly assigned (1:1:1:1) with a computer
      generated assignment schedule to control (no tracker or incentives), Fitbit Zip
      activity tracker, tracker plus charity incentives, or tracker plus cash
      incentives. Participants had to be English speaking, full-time employees, aged 21
      65 years, able to walk at least ten steps continuously, and non-pregnant.
      Incentives were tied to weekly steps, and the primary outcome, moderate-to
      vigorous physical activity (MVPA) bout min per week, was measured via a sealed
      accelerometer and assessed on an intention-to-treat basis at 6 months (end of
      intervention) and 12 months (after a 6 month post-intervention follow-up period).
      Other outcome measures included steps, participants meeting 70 000 steps per week
      target, and health-related outcomes including weight, blood pressure, and quality
      of-life measures. This trial is registered at ClinicalTrials.gov, number
      NCT01855776. FINDINGS: Between June 13, 2013, and Aug 15, 2014, 800 participants
      were recruited and randomly assigned to the control (n=201), Fitbit (n=203),
      charity (n=199), and cash (n=197) groups. At 6 months, compared with control, the
      cash group logged an additional 29 MVPA bout min per week (95% CI 10-47;
      p=0.0024) and the charity group an additional 21 MVPA bout min per week (2-39;
      p=0.0310); the difference between Fitbit only and control was not significant (16
      MVPA bout min per week [-2 to 35; p=0.0854]). Increases in MVPA bout min per week
      in the cash and charity groups were not significantly greater than that of the
      Fitbit group. At 12 months, the Fitbit group logged an additional 37 MVPA bout
      min per week (19-56; p=0.0001) and the charity group an additional 32 MVPA bout
      min per week (12-51; p=0.0013) compared with control; the difference between cash
      and control was not significant (15 MVPA bout min per week [-5 to 34; p=0.1363]).
      A decrease in physical activity of -23 MVPA bout min per week (95% CI -42 to -4;
      p=0.0184) was seen when comparing the cash group with the Fitbit group. There
      were no improvements in any health outcomes (weight, blood pressure, etc) at
      either assessment. INTERPRETATION: The cash incentive was most effective at
      increasing MVPA bout min per week at 6 months, but this effect was not sustained
      6 months after the incentives were discontinued. At 12 months, the activity
      tracker with or without charity incentives were effective at stemming the
      reduction in MVPA bout min per week seen in the control group, but we identified
      no evidence of improvements in health outcomes, either with or without
      incentives, calling into question the value of these devices for health
      promotion. Although other incentive strategies might generate greater increases
      in step activity and improvements in health outcomes, incentives would probably
      need to be in place long term to avoid any potential decrease in physical
      activity resulting from discontinuation. FUNDING: Ministry of Health, Singapore.

PMID- 27717767
TI  - Valuable steps ahead: promoting physical activity with wearables and incentives.

PMID- 27717768
TI  - Comparative effectiveness and cost-effectiveness of treat-to-target versus
      benefit-based tailored treatment of type 2 diabetes in low-income and middle
      income countries: a modelling analysis.
AB  - BACKGROUND: Optimal prescription of blood pressure, lipid, and glycaemic control
      treatments for adults with type 2 diabetes remains unclear. We aimed to compare
      the effectiveness and cost-effectiveness of two treatment approaches for diabetes
      management in five low-income and middle-income countries. METHODS: We developed
      a microsimulation model to compare a treat-to-target (TTT) strategy, aiming to
      achieve target levels of biomarkers (blood pressure <130/80 mm Hg, LDL <2.59
      mmol/L, and HbA1c <7% [ie, 53.0 mmol/mol]), with a benefit-based tailored
      treatment (BTT) strategy, aiming to lower estimated risk for complications (to a
      10 year cardiovascular risk <10% and lifetime microvascular risk <5%) on the
      basis of age, sex, and biomarker values. Data were obtained from cohorts in
      China, Ghana, India, Mexico, and South Africa to span a spectrum of risk
      profiles. FINDINGS: The TTT strategy recommended treatment to a larger number of
      people-who were generally at lower risk of diabetes complications-than the BTT.
      The BTT strategy recommended treatment to fewer people at higher risk. Compared
      with the TTT strategy, the BTT strategy would be expected to avert 24.4-30.5%
      more complications and be more cost-effective from a societal perspective (saving
      US$4.0-300.0 per disability-adjusted life-year averted in the countries
      simulated). Alternative treatment thresholds, matched by total cost or population
      size treated, did not change the comparative superiority of the BTT strategy, nor
      did titrating treatment using fasting plasma glucose (for areas without HbA1c
      testing). However, if insulin were unavailable, the BTT strategy would no longer
      be superior for preventing microvascular events and was superior only for
      preventing cardiovascular events. INTERPRETATION: A BTT strategy is more
      effective and cost-effective than a TTT strategy in low-income and middle-income
      countries for prevention of both cardiovascular and microvascular complications
      of type 2 diabetes. However, the superiority of the BTT strategy for averting
      microvascular complications is contingent on insulin availability. FUNDING:
      Rosenkranz Prize for Healthcare Research in Developing Countries and US National
      Institutes of Health (U54 MD010724, DP2 MD010478).

PMID- 27717769
TI  - Peering into the brain to predict behavior: Peer-reported, but not self-reported,
      conscientiousness links threat-related amygdala activity to future problem
      drinking.
AB  - Personality traits such as conscientiousness as self-reported by individuals can
      help predict a range of outcomes, from job performance to longevity. Asking
      others to rate the personality of their acquaintances often provides even better
      predictive power than using self-report. Here, we examine whether peer-reported
      personality can provide a better link between brain function, namely threat
      related amygdala activity, and future health-related behavior, namely problem
      drinking, than self-reported personality. Using data from a sample of 377 young
      adult university students who were rated on five personality traits by peers, we
      find that higher threat-related amygdala activity to fearful facial expressions
      is associated with higher peer-reported, but not self-reported,
      conscientiousness. Moreover, higher peer-reported, but not self-reported,
      conscientiousness predicts lower future problem drinking more than one year
      later, an effect specific to men. Remarkably, relatively higher amygdala activity
      has an indirect effect on future drinking behavior in men, linked by peer
      reported conscientiousness to lower future problem drinking. Our results provide
      initial evidence that the perceived conscientiousness of an individual by their
      peers uniquely reflects variability in a core neural mechanism supporting threat
      responsiveness. These novel patterns further suggest that incorporating peer
      reported measures of personality into individual differences research can reveal
      novel predictive pathways of risk and protection for problem behaviors.

PMID- 27717771
TI  - In vitro culture of Babesia bovis in a bovine serum-free culture medium
      supplemented with insulin, transferrin, and selenite.
AB  - Bovine serum is an important factor for the optimal growth of Babesia bovis in
      vitro. This protozoan can be cultured in M-199 with Earle's salts medium (M-199)
      supplemented with 40% bovine serum (BS). In the present study, four media were
      assessed along with the control medium M-199. The effect on the proliferation of
      B. bovis in vitro was tested when these media were combined with insulin (Ins),
      transferrin (Trans) and selenite (Sel) in the absence of bovine serum. Treatment
      with Advanced DMEM/F12 medium (A-DMEM/F12) achieved the highest percentage of
      parasitized erythrocytes (PPE), reaching a maximum value of 9.59%. A-DMEM/F12
      medium supplemented with a mixture of Ins (2000 mg/L), Trans (1100 mg/L), and Sel
      (1.34 mg/L) allowed for the adaptation and proliferation of B. bovis without
      bovine serum, showed a constant increase in PPE, and reached a maximum value of
      9.7% during seven cycles of in vitro culture. It was concluded that continuous
      proliferation of B. bovis in vitro could be achieved using A-DMEM/F12 medium
      supplemented with Ins-Trans-Sel, without bovine serum. After adaptation for
      proliferation in serum-free medium, the B. bovis strain of parasites could have
      future use in the study of this economically important protozoan species that
      affects cattle.

PMID- 27717770
TI  - Genome-wide association analysis of secondary imaging phenotypes from the
      Alzheimer's disease neuroimaging initiative study.
AB  - The aim of this paper is to systematically evaluate a biased sampling issue
      associated with genome-wide association analysis (GWAS) of imaging phenotypes for
      most imaging genetic studies, including the Alzheimer's Disease Neuroimaging
      Initiative (ADNI). Specifically, the original sampling scheme of these imaging
      genetic studies is primarily the retrospective case-control design, whereas most
      existing statistical analyses of these studies ignore such sampling scheme by
      directly correlating imaging phenotypes (called the secondary traits) with
      genotype. Although it has been well documented in genetic epidemiology that
      ignoring the case-control sampling scheme can produce highly biased estimates,
      and subsequently lead to misleading results and suspicious associations, such
      findings are not well documented in imaging genetics. We use extensive
      simulations and a large-scale imaging genetic data analysis of the Alzheimer's
      Disease Neuroimaging Initiative (ADNI) data to evaluate the effects of the case
      control sampling scheme on GWAS results based on some standard statistical
      methods, such as linear regression methods, while comparing it with several
      advanced statistical methods that appropriately adjust for the case-control
      sampling scheme.

PMID- 27717772
TI  - Invasion by Trichinella spiralis infective larvae affects the levels of
      inflammatory cytokines in intestinal epithelial cells in vitro.
AB  - As we all know, invasion of host intestinal epithelium is very important for T.
      spiralis to complete successfully their life cycle. However, the mechanisms that
      the intestinal infective larvae (IIL) invade and migrate in the intestinal
      epithailial cells (IECs) remain unclear until now. The related researches have
      been hindered since a readily operable in vitro normal model. In our earlier
      study, an in vitro normal IEC invasion model was established for the first time,
      and the abilities of the normal IECs to initiate mucosal inflammatory responses
      to invasion by the IIL in vitro were evaluated in this study. When the IIL were
      overlaid on the normal mouse IEC monolayers, they quickly within seconds invaded
      the monolayers and move within the IECs, leaving trails of damaged cells. Then
      the larvae were found to have started their molting at 12 h, and the complete
      cuticle was found at 24 h. The percentage of the first molt in the larvae was
      about 62.3%, and the percentage of the 2nd-4th molt was about 38.2% at 36 h. Real
      time PCR showed that the mRNA levels of interleukin-1beta (IL-1beta), IL-8,
      epithelial neutrophil-activating peptide 78 (ENA-78), inducible nitric oxide
      synthase (iNOS), and monocyte chemotactic protein 2 (MCP-2) were elevated in the
      IECs after 7 h of infection after invasion by the IIL, and their levels were
      enhanced with the increase of larvae number. No changes in tumor necrosis factor
      alpha (TNF-alpha) mRNA were observed after the IIL invasion. Secretion increases
      of IL-1beta and IL-8 from the IEC monolayers invaded by T. spiralis were also
      detected by ELISA. Secretion increases of proinflammatory cytokines and
      inflammatory mediators in normal IECs can launch the acute inflammatory in
      response to the IIL invasion. This study would be helpful in further
      investigating the relationship between the host and T. spiralis, and the immune
      escape mechanisms of the niche established by T. spiralis.

PMID- 27717773
TI  - Development and evaluation of molecular methods for detection of Cryptosporidium
      spp. in human clinical samples.
AB  - Cryptosporidiosis is predominantly a gastrointestinal disease of humans and other
      animals, caused by various species of protozoan parasites representing the genus
      Cryptosporidium. Detection of Cryptosporidium spp. in human clinical samples is
      central to the prevention, surveillance and control of cryptosporidiosis,
      particularly given that there is presently no broadly applicable treatment
      regimen for this disease. A non-radioactive, genus specific DNA dot blot
      hybridization assay was developed using Digoxigenin (DIG) labelled probes to
      detect Cryptosporidium DNA in human clinical samples. Four hundred fifty (n =
      450) clinical samples were subjected to microscopic examination, Polymerase Chain
      Reaction assay (PCR), Dot blot hybridization assay and Real Time PCR assay. A
      total of forty-one (n = 41) samples were positive by microscopy, forty-two (n =
      42) by both PCR assay and dot blot hybridization assay and forty-three (n = 43)
      by Real Time PCR assay. Dot blot hybridization assay with a sensitivity of 95.5%
      and specificity of 99.75% could be an ideal choice for routine investigation of a
      large number of samples in a clinical setting as well as field.

PMID- 27717774
TI  - Appetite regulating factors in pacu (Piaractus mesopotamicus): Tissue
      distribution and effects of food quantity and quality on gene expression.
AB  - The pacu Piaractus mesopotamicus is an omnivorous fish considered a promising
      species for aquaculture. Little is known about the endocrine regulation of
      feeding in this species. In this study, transcripts for orexin, cocaine and
      amphetamine regulated transcript (CART), cholecystokinin (CCK) and leptin were
      isolated in pacu. Orexin, CCK and leptin have widespread mRNA distributions in
      brain and periphery, CART is limited to the brain. To examine the role of these
      peptides in the regulation of feeding and energy status, mRNA expression levels
      were compared between fed and fasted fish and around feeding time. Both orexin
      and CART brain expressions were affected by fasting and displayed periprandial
      changes, suggesting a role in both short- and long-term regulation of feeding.
      CCK intestinal expression decreased in fasted fish and displayed periprandial
      changes, suggesting CCK acts as a peripheral satiety factor. Leptin was not
      affected by fasting but displayed periprandial changes, suggesting a role as a
      short-term regulator. To examine if these peptides are affected by diet, brain
      and gut expressions were assessed in fish fed with different diets containing soy
      protein concentrate. Food intake, weight gain and expressions of orexin, CART,
      CCK and leptin were little affected by replacement of fish protein with soy
      protein, suggesting that pacu is able to tolerate and grow well with a diet rich
      in plant material. Overall, our results suggest that orexin, CART, CCK and leptin
      are involved in the physiology of feeding of pacu and that their expressions are
      little affected by plant-based diets.

PMID- 27717775
TI  - The Effect of l-Arginine on Dural Healing After Experimentally Induced Dural
      Defect in a Rat Model.
AB  - BACKGROUND: Incomplete repair of the dura mater may result in numerous
      complications such as cerebrospinal fluid leakage and meningitis. For this
      reason, accurate repair of the dura mater is essential. In this study, the effect
      of systemic and local supplementation of l-arginine on dural healing was
      evaluated. METHODS: Thirty male Wistar rats were used and divided into control,
      local, and systemic l-arginine groups, with 10 rats in each. In each group, a 5
      mm experimental incision was made at the lumbar segment of the dura mater and
      cerebrospinal fluid leakage was induced. Each group was divided into 2 subgroups
      and at the end of the first and sixth weeks, the rats were killed and the damaged
      segments of the dura were separated, histologically evaluated and the dural
      healing indicators including cell types, granulation tissue formation, collagen
      deposit, and vascularization were compared between groups. RESULTS: The
      systematic supplementation of l-arginine showed a significant effect in dural
      healing compared with the control group. After the first week, granulation
      formation increased considerably (P < 0.031), and after 6 weeks, collagen
      deposition and neovascularization were significantly different compared with the
      control group (P < 0.030; P < 0.009). In comparison between different groups at
      the end of the first and sixth weeks, maximum changes in healing indicators were
      observed in the systemic group and the least variations were related to the
      control group. CONCLUSIONS: The systemic supplementation of l-arginine may
      accelerate dural healing by increasing the level of granulation tissue formation,
      collagen deposition, and vascularization.

PMID- 27717776
TI  - Predictors of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid
      Hemorrhage with Asymptomatic Angiographic Vasospasm on Admission.
AB  - BACKGROUND: Risk of delayed cerebral ischemia (DCI) in patients with aneurysmal
      subarachnoid hemorrhage (aSAH) with asymptomatic angiographic vasospasm on
      admission is unclear in the literature. The goal of this study is to identify
      predictors of clinical DCI in this group of patients. METHODS: An exploratory
      subgroup analysis was conducted in the SAHIT (Subarachnoid Hemorrhage
      International Trialists) data repository to identify predictors of clinical DCI
      in patients with good-grade aSAH (World Federation of Neurological Surgeons grade
      I and II) with angiographic vasospasm on admission. Predictors considered include
      age, sex, systolic blood pressure at presentation, World Federation of
      Neurological Surgeon grade, Fisher grade, aneurysm size and location, treatment
      modality, hydrocephalus requiring external ventricular drain insertion, and
      severity of vasospasm. The predictors were ranked based on dominance analysis
      with R2 as fit statistics and assessed in a set of logistic regression analysis
      models. RESULTS: Four data sets out of 16 studies in the SAHIT database were
      analyzed, with a total of 4125 patients. One hundred and ninety-one patients
      (4.6%) had asymptomatic angiographic vasospasm at admission. Of those, 78
      patients (40.8%) developed clinical DCI. Univariate analysis showed significant
      associations between severe vasospasm on admission and development of clinical
      DCI (odds ratio, 9.5, 95% confidence interval, 2.07-43.50; P = 0.004). None of
      the studied predictors was associated with the development of clinical DCI on
      multivariate analysis. CONCLUSIONS: Asymptomatic angiographic vasospasm in
      patients with good-grade aSAH on admission is uncommon. Further studies are
      needed to identify high-risk patients for the development of DCI in the context
      of asymptomatic early vasospasm.

PMID- 27717777
TI  - Application of Unilateral C2 Translaminar Screw in the Treatment for Atlantoaxial
      Instability as an Alternative or Salvage of Pedicle Screw Fixation.
AB  - OBJECTIVE: To analyze the clinical outcomes of our experience with the unilateral
      C2 translaminar screw technique and evaluate its feasibility as an alternative or
      salvage of the pedicle screw. METHODS: Eleven consecutive adult patients with
      atlantoaxial instability who underwent hybrid fixation techniques using
      unilateral translaminar screw combined with contralateral C2 pedicle screw and
      bilateral C1 LMS via posterior arch from January 2010 to December 2013 were
      retrospectively investigated. The surgical techniques and treatment procedures
      were described, and clinical symptoms, neurologic function, and imaging
      appearance were evaluated. RESULTS: The average age in our series was 40.9 years.
      No vascular or neurologic injuries occurred. No hardware failure or breach of C2
      lamina or pedicle was observed in postoperative radiographs or computed
      tomography scans. Good bone union was achieved in all patients. There were no
      cases of screw pullout or pseudarthrosis. CONCLUSIONS: Patients with variant
      vertebral artery or osseous anomaly are good candidates for the hybrid
      translaminar screw technique as an alternative to or salvage of C2 pedicle screw.

PMID- 27717778
TI  - The Burgeoning Roots of Socioeconomic Inequalities in Health: The Legacy Effect.

PMID- 27717779
TI  - First characterization of the CD4 and CD8 T-cell responses to QuantiFERON-TB
      Plus.
AB  - INTRODUCTION: QuantiFERON(r)-TB Gold Plus (QFT-Plus) is the new generation of
      QuantiFERON-TB Gold In-Tube test to identify latent tuberculosis infection
      (LTBI). QFT-Plus includes TB1 and TB2 tubes which contain selected Mycobacterium
      tuberculosis (Mtb) peptides designed to stimulate both CD4 and CD8 T-cells. Aim
      of this study is the flow cytometric characterization of the specific CD4 and CD8
      T-cell responses to Mtb antigens contained within QFT-Plus. METHODS: We enrolled
      27 active tuberculosis (TB) patients and 30 LTBI individuals. Following
      stimulation with TB1 and TB2, antigen-specific T-cells were characterized by flow
      cytometry. Data were also correlated with the grade of TB severity. RESULTS: TB1
      mainly elicited a CD4 T-cell response while TB2 induced both CD4 and CD8
      responses. Moreover, the TB2-specific CD4 response was detected for both active
      TB and LTBI patients, whereas the TB2-specific CD8 response was primarily
      associated with active TB (p = 0.01). CONCLUSIONS: To our knowledge, we report
      the first characterization of the CD4 and CD8 T-cell response to QFT-Plus. CD8 T
      cell response is mainly due to TB2 stimulation which is largely associated to
      active TB. These results provide a better knowledge on the use of this assay.

PMID- 27717780
TI  - HIV-infection and psychiatric illnesses - A double edged sword that threatens the
      vision of a contained epidemic: The Greater Stockholm HIV Cohort Study.
AB  - CONTEXT: The Greater Stockholm HIV Cohort Study is an initiative to provide
      longitudinal information regarding the health of people living with HIV.
      OBJECTIVE: Our aim was to explore the prevalence of HIV and its association with
      psychiatric co-morbidities. DESIGN, SETTING AND PARTICIPANTS: All patients with a
      recorded diagnosis of HIV (any position of the ICD-10 codes B20-B24) were
      identified during the period 2007-2014 and related to the total population in
      Stockholm by January 1, 2015, N = 2.21 million. The age at diagnosis, gender, and
      first occurrence of an HIV diagnosis was recorded. Analyses were done by age and
      gender. Prevalence of psychiatric co-morbidities amongst HIV patients were
      recorded. MAIN OUTCOME MEASURES: Age-adjusted odds ratios with 95% confidence
      intervals were calculated with logistic regression for prevalent psychiatric co
      morbidities in HIV infected individuals compared to the prevalence in the general
      population. RESULTS: The total prevalence of HIV was 0.16%; females 0.10% (n =
      1134) and males 0.21% (n = 2448). HIV-infected people were more frequently
      diagnosed with psychiatric illnesses and drug abuse. In females and males with
      HIV-diagnosis respectively, drug dependence disorder was 7.5 (7.76% vs 1.04%) and
      5.1 (10.17% vs 1.98%) times higher, psychotic disorders were 6.3 (2.65% vs 0.42%)
      and 2.9 (1.43% vs 0.49%) times higher, bipolar disorder was 2.5 (1.41% vs 0.57%)
      and 3 (1.02% vs 0.34%) times higher, depression diagnosis was 1.5 (8.47% vs
      5.82%) and 3.4 (10.17% vs 2.97%) higher, trauma-related disorder was 1.5 (6.00%
      vs 4.10%) respectively 2.9 (4.45% vs 1.56%) times higher, anxiety disorder was
      1.2 (6.88% vs 5.72%) and 2.2 (6.54% vs 2.93%) times higher than in their non
      infected peers. CONCLUSION: Despite effective ART, many individuals with HIV have
      an impaired mental health and a history of drug abuse that may threaten the
      vision of a contained epidemic.

PMID- 27717781
TI  - 1,3-beta-d-Glucan testing is highly specific in patients undergoing dialysis
      treatment.
AB  - BACKGROUND: The aim of this combined in-vitro and in-vivo study was to
      investigate whether state of the art dialysis modalities produce false positive
      serum 1,3-beta-d-Glucan (BDG) levels. METHODS: Dialysis fluid for simulated
      dialysis treatments was spiked with BDG from different sources. Samples were
      taken from the dialysate and dialyzer blood compartments at various time points.
      In addition, serum samples were obtained in three groups of patients without
      invasive fungal disease: a.) twelve patients on chronic hemodialysis
      (HD)/hemodiafiltration (HDF); b.) ten patients on continuous ambulatory
      peritoneal dialysis (CAPD); and c.) ten patients with stable chronic kidney
      disease (CKD) but without dialysis. RESULTS: Median BDG levels in BDG spiked
      dialysate were 3250.9, 2050.4, and 390.1 pg/ml respectively. All corresponding
      samples from the blood compartments were BDG negative. In HD/HDF patients no
      increase of serum BDG levels could be observed over the duration of treatment.
      71/72 BDG tests in this group remained negative. BDG tests were also negative in
      9/10 CAPD patients, both in in- and outflow dialysates as well as in all ten
      patients with CKD. CONCLUSION: We conclude that state of the art renal
      replacement therapies using up-to-date treatments are not a cause of falsely
      elevated serum BDG levels.

PMID- 27717782
TI  - Incidence and mortality of herpes simplex encephalitis in Denmark: A nationwide
      registry-based cohort study.
AB  - OBJECTIVES: We aimed to investigate the incidence and mortality of herpes simplex
      encephalitis (HSE) in a nationwide cohort. METHODS: From the Danish National
      Patient Registry, we identified all adults hospitalised with a first-time
      diagnosis of HSE in Denmark during 2004-2014. The HSE diagnoses were verified
      using medical records and microbiological data. Patients were followed for
      mortality through the Danish Civil Registry System. We estimated age-standardised
      incidence rates of HSE and 30-day, 60-day, and 1-year cumulative mortality.
      Furthermore, we assessed whether calendar year, age, gender, level of
      comorbidity, virus type, and department type was associated with HSE mortality.
      RESULTS: We identified a total of 230 cases of HSE. Median age was 60.7 years
      (interquartile range: 49.3-71.6). The overall incidence rate was 4.64 cases per
      million population per year (95% confidence interval: 4.06-5.28). The cumulative
      mortality within 30 days, 60 days, and 1 year of the HSE admission was 8.3%,
      11.3%, and 18.6%, respectively. Advanced age and presence of comorbidity were
      associated with increased 60-day and 1-year mortality. CONCLUSIONS: This
      nationwide study of verified HSE found a higher incidence than reported in
      previous nationwide studies. Presence of comorbidity was identified as a novel
      adverse prognostic factor. Mortality rates following HSE remain high.

PMID- 27717784
TI  - The prevalence of non-tuberculous mycobacterial infections in mainland China:
      Systematic review and meta-analysis.
AB  - Despite increasing attention towards the non-tuberculous mycobacterial (NTM)
      diseases, the overall epidemiological information remains unavailable for China.
      A systematic review and meta-analysis was conducted using data of 105 qualified
      publications from Chinese mainland. The assay demonstrated that the prevalence of
      NTM infections among tuberculosis suspects was 6.3% (5.4%-7.4%) in mainland,
      while the Southeastern region had the highest NTM prevalence at 8.6% (7.1%
      10.5%). In Northern China, slow growing mycobacteria (SGM) consistituted 63.7% of
      all the NTM isolates, while this rate in Southern China was 53.0%. More rapid
      growing mycobacteria (RGM) were present in southern China than the northern (chi2
      = 57.996, P < 0.001). According to the coastal provinces' data (from north to
      south), the NTM prevalence rate and the number of isolated NTM species increased
      apparently in accordance with geographic latitude. The information obtained in
      this assay will facilitate the NTM disease diagnosis and screening policy making
      in China.

PMID- 27717785
TI  - Comparison of patients treated with or without a spacer in two stage revision hip
      arthroplasty for periprosthetic joint infection.

PMID- 27717783
TI  - Tuberculosis-diabetes co-morbidity is characterized by heightened systemic levels
      of circulating angiogenic factors.
AB  - BACKGROUND: Tuberculosis-diabetes co-morbidity (TB-DM) is characterized by
      increased inflammation with elevated circulating levels of inflammatory cytokines
      and other factors. Circulating angiogenic factors are intricately involved in the
      angiogenesis-inflammation nexus. METHODS: To study the association of angiogenic
      factors with TB-DM, we examined the systemic levels of VEGF-A, VEGF-C, VEGF-D,
      VEGF-R1, VEGF-R2, VEGF-R3 in individuals with either TB-DM (n = 44) or TB alone
      (n = 44). RESULTS: Circulating levels of VEGF-A, C, D, R1, R2 and R3 were
      significantly higher in TB-DM compared to TB individuals. Moreover, the levels of
      VEGF-A, C, R2 and/or R3 were significantly higher in TB-DM with bilateral or
      cavitary disease or with hemoptysis, suggesting an association with both disease
      severity and adverse clinical presentation. The levels of these factors also
      exhibited a significant positive relationship with bacterial burdens and HbA1c
      levels. In addition, VEGF-A, C and R2 levels were significantly higher (at 2
      months of treatment) in culture positive compared to culture negative TB-DM
      individuals. Finally, the circulating levels of VEGF-A, C, D, R1, R2 and R3 were
      significantly reduced following successful chemotherapy at 6 months. CONCLUSION:
      Our data demonstrate that TB-DM is associated with heightened levels of
      circulating angiogenic factors, possibly reflecting both dysregulated
      angiogenesis and exaggerated inflammation.

PMID- 27717786
TI  - Production, purification, and characterization of metalloprotease from Candida
      kefyr 41 PSB.
AB  - A thermostable metalloprotease, produced from an environmental strain of Candida
      kefyr 41 PSB, was purified 16 fold with a 60% yield by cold ethanol precipitation
      and affinity chromatography (bentonite-acrylamide-cysteine microcomposite). The
      purified enzyme appeared as a single protein band at 43kDa. Its optimum pH and
      temperature points were found to be 7.0 and 105 degrees C, respectively. Km and
      Vmax values of the enzyme were determined to be 3.5mg/mL and 4.4MUmolmL-1min-1,
      1.65mg/mL and 6.1MUmolmL-1min-1, using casein and gelatine as the substrates,
      respectively. The activity was inhibited by using ethylenediamine tetraacetic
      acid (EDTA), indicating that the enzyme was a metalloprotease. Stability of the
      enzyme was investigated by using thermodynamic and kinetic parameters. The
      thermal inactivation profile of the enzyme conformed to the first order kinetics.
      The half life of the enzyme at 95, 105, 115, 125 and 135 degrees C was 1310, 610,
      220, 150, and 86min, respectively.

PMID- 27717787
TI  - A protease-resistant alpha-galactosidase from Pleurotus djamor with broad pH
      stability and good hydrolytic activity toward raffinose family oligosaccharides.
AB  - An acidic alpha-galactosidase designated as PDGI (Pleurotus djamor alpha
      galactosidase) was purified to homogeneity with 290-fold purification and a
      specific activity of 52.18 units/mg by means of ion exchange chromatography and
      gel filtration chromatography. PDGI is a monomeric protein exhibiting a molecular
      mass of 60kDa in SDS-PAGE and gel filtration. The optimum pH and temperature of
      the enzyme with pNPGal as substrate were 5.0 and 53.5 degrees C, respectively. It
      displayed great pH stability within the pH range 3.0-10.0. Besides, the enzyme
      harbored remarkable resistance to acid protease and varying degrees of tolerance
      to other proteases: trypsin>collagenase Type-I>alpha-chymotrypsin neutral
      protease>proteinaseK. It was strongly inhibited by K+, Cd2+, Cu2+, Hg2+, Al3+,
      Fe3+ and Ag + ions. The chemical modification reagents diethypyrocarbonate
      (DEPC), 2,3-butanedione (DIC) and trinitrophenol (TNBS) increased the activity of
      PDGI 1.5-fold whereas N-bromosuccinimide (NBS) and parachloro-mercuri-benzoate
      (PCMB) drastically suppressed its activity. PDGI displayed activity toward
      stachyose and raffinose. The Km values for hydrolysis of pNPGal, stachyose and
      raffinose were 0.76, 7.63 and 6.29mM, respectively. Furthermore, PDGI degraded
      raffinose and sthachyose. These results suggest that PDGI has great potential for
      elimination of the non-digestible and flatulence-causing oligosaccharides
      stachyose and raffinose from legumes.

PMID- 27717788
TI  - In vitro and in silico studies of the interaction of three tetrazoloquinazoline
      derivatives with DNA and BSA and their cytotoxicity activities against MCF-7, HT
      29 and DPSC cell lines.
AB  - In this study, the interaction of three [1,2,3,4]tetrazolo[5,1-b]-quinazolin-8
      one derivatives with salmon sperm DNA and BSA was investigated experimentally and
      theoretically. Fluorescence and absorption spectroscopy techniques were applied
      to determine the probable interaction mechanism and correlated binding constants
      and thermodynamic parameters. It was found that the compounds intercalate into
      the DNA duplex via minor groove in a moderately strong fashion with the binding
      constants of 104M-1. The values of binding constant for the interaction with BSA
      at different temperatures were also calculated to be in the range of 1.06*103
      3.54*108M-1 indicating the relatively high propensity of the compounds to BSA. In
      vitro cytotoxicity studies on the effect of the compounds on MCF-7 and HT-29
      cancerous cell lines as well as DPSC normal cell line were performed using MTT
      assay. It was observed that the compounds exhibited selective inhibitory effect
      against cancer cell growth. Moreover, each of the title compounds was separately
      docked to DNA and BSA using Autodock Vina as a molecular docking program. The
      obtained theoretical results were in good agreement with those obtained from
      Experimental studies.

PMID- 27717789
TI  - The use of sugar beet pulp lignin for the production of vanillin.
AB  - The objectives of this work is to produce vanillin from sugar beet pulp by lignin
      oxidation and evaluate the effect of process parameters (temperature, partial
      pressure of oxygen, reaction time, CuSO4 as a catalyst) on the yield of vanillin.
      Purification and separation of vanillin from pressurized extract was carried out
      by organic solvent and crystallization. HPLC, FT-IR, H NMR, GC/MS and DSC methods
      were performed to approve the vanillin crystal. Results showed that production of
      vanillin was significantly affected by four parameters, and an optimal conditions
      for production of vanillin was found 4.3bar for an oxygen partial pressure under
      a temperature of 156 degrees C and duration of time 30min without CuSO4,
      corresponding to 1439.3mg/100g vanillin. Thermal property of syntesis vanillin
      was coincide to DSC pure vanillin curve but there were differences in DeltaH
      degrees f and DeltaHc.

PMID- 27717790
TI  - Development of the Hypogonadism Impact of Symptoms Questionnaire Short Form:
      Qualitative Research.
AB  - INTRODUCTION: Hypogonadism in men is often associated with poor libido, erectile
      dysfunction, irritability, fatigue, and psychological and relationship problems.
      Many of these symptoms can be best assessed through patient report. The 28-item
      Hypogonadism Impact of Symptoms Questionnaire (HIS-Q) was developed to evaluate
      hypogonadism symptoms in men with low testosterone in the context of clinical
      trials. AIM: To develop a briefer version of the HIS-Q that could be practical
      for use in treatment settings. METHODS: Participants with low testosterone levels
      and symptoms consistent with hypogonadism were recruited through clinical sites.
      Focus groups and interviews were conducted to elicit symptom concepts and
      identify those that were most relevant to patients, including changes as a
      consequence of treatment. MAIN OUTCOME MEASURES: Systematic analysis of the
      qualitative data and expert clinician input were used to develop the HIS-Q short
      form (HIS-Q-SF). One-on-one cognitive interviews were conducted to confirm the
      content validity of the HIS-Q-SF. RESULTS: Thirty-five men participated in this
      qualitative research. Concept elicitation was conducted through focus group
      discussions (n = 18) and telephone interviews (n = 2); then, the draft HIS-Q-SF
      was evaluated through cognitive interviews (n = 15). The mean age of total sample
      was 53.2 +/- 6.8 years, and the mean serum total testosterone level was 184.9 +/-
      55.2 ng/dL. Results suggest that the HIS-Q-SF has demonstrated content validity,
      including the content coverage, comprehensibility, and the appropriateness of the
      response options and recall period. The final version of the HIS-Q-SF includes 17
      items and is aligned with the original longer version of the instrument.
      CONCLUSION: The HIS-Q-SF is a comprehensive measurement of hypogonadism symptom
      severity in men. Content coverage and content validity were confirmed. The
      instrument will be evaluated further to establish the psychometric
      characteristics and to assess the utility of the measurement in clinical
      treatment settings.

PMID- 27717791
TI  - Patient preferences for inflammatory bowel disease treatment objectives.
AB  - BACKGROUND: There is currently little evidence about what treatment objectives
      most interest patients with inflammatory bowel disease (IBD). AIMS: To determine
      patient preferences regarding IBD treatment objectives, specially the attributes
      they value most and the symptoms to be controlled as a priority. METHODS:
      Prospective, observational, anonymous study conducted in 117 outpatients with
      Crohn's disease or ulcerative colitis. RESULTS: The most important treatment
      objectives from the patients' perspective were: improving quality of life (40.2%
      of patients), and completely resolving symptoms (33.3%). Only 12.8% of patients
      indicated having a completely normal colonoscopy as a preferred objective. The
      symptoms the patients considered to be most important when prioritizing their
      control were: abdominal pain (23.1% of patients), and bowel movement urgency
      (17.1%). The preferred treatment objectives were similar for Crohn's disease and
      ulcerative colitis patients. CONCLUSIONS: Improving quality of life and
      completely controlling symptoms are the priority treatment objectives for IBD
      patients, with abdominal pain being the most important symptom. Conversely,
      therapeutic objective target goals proposed by physicians, such as healing the
      mucosal lesions, are not a priority for most patients. This indicates that there
      are discrepancies between patient and physician expectations, which should be
      taken into account if a patient-centered care model is to be implemented.

PMID- 27717792
TI  - Beta blockers and cirrhosis, 2016.
AB  - To date, non-selective beta blockers (NSBBs) are a cornerstone in the treatment
      of portal hypertension. During the last years, our understanding of the potential
      benefits of early initiation of NSBB treatment, their effects beyond the
      prevention of variceal bleeding (i.e., their non-hemodyamic effects), as well as
      potential detrimental effects in patients with advanced disease has continuously
      evolved. In addition, we have learned that not all NSBBs are equal. Due to its
      additional anti-alpha1-adrenergic activity, carvedilol has been shown to be more
      potent in decreasing portal pressure, but might lead to more pronounced decreases
      in systemic arterial pressure, when compared to conventional NSBBs. It might be
      particularly beneficial in 'early' portal hypertension, when potential
      detrimental effects on systemic hemodynamics are less critical. In contrast,
      there is increasing evidence that the use of carvedilol or high NSBB doses should
      be carefully scrutinized in patients with severe or refractory ascites. Our
      review summarizes the current knowledge on the use of NSBBs for preventing
      variceal bleeding and other decompensating events and provides guidance for their
      safe use in hemodynamically 'vulnerable' patient populations. Finally, we also
      highlight areas for further research.

PMID- 27717793
TI  - The effect of CYP3A5 genetic polymorphisms on adverse events in patients with
      ulcerative colitis treated with tacrolimus.
AB  - BACKGROUND: Tacrolimus is an immunosuppressive agent, used in the remission
      induction therapy of ulcerative colitis (UC). AIMS: We investigated the
      correlation between CYP3A5 genetic polymorphisms and the adverse events in
      patients with UC. The pharmacokinetics of tacrolimus after oral administration
      were also analyzed. METHODS: We enrolled 29 hospitalized patients with UC
      received oral tacrolimus. Genotyping for CYP3A5 A6986G (rs776746) was performed
      using Custom TaqMan(r) SNP genotyping assays. Adverse events, concentration and
      dose (C/D) ratios and clinical outcomes were investigated. RESULTS: CYP3A5
      expressers and non-expressers were 16 and 13, respectively. C/D ratios of CYP3A5
      expressers were significantly lower compared to non-expressers. The response rate
      in CYP3A5 non-expressers was relatively higher in the early phase of treatment
      compared to expressers, but not statistically significant. The incidence of
      overall adverse events was significantly higher in CYP3A5 expressers than in non
      expressers (P=0.034, chi-squared test). In particular, the incidence of
      nephrotoxicity was significantly higher in CYP3A5 expressers compared to non
      expressers (P=0.027, chi-squared test). All of the nephrotoxicity were reversible
      and resolved by discontinuation or dose reduction of tacrolimus. CONCLUSION: The
      adverse events especially nephrotoxicity were frequently observed in CYP3A5
      expressers. CYP3A5 expressers should be paid attention to the onset of
      nephrotoxicity.

PMID- 27717795
TI  - Antibiotics, intestinal dysbiosis and risk of celiac disease.

PMID- 27717794
TI  - Disease patterns in late-onset ulcerative colitis: Results from the IG-IBD "AGED
      study".
AB  - BACKGROUND: Late-onset UC represents an important issue for the near future, but
      its outcomes and relative therapeutic strategies are yet poorly studied. AIM: To
      better define the natural history of late-onset ulcerative colitis. METHODS: In a
      multicenter retrospective study, we investigated the disease presentation and
      course in the first 3 years in 1091 UC patients divided into 3 age-groups:
      diagnosis >=65years, 40-64 years, and <40years. Disease patterns, medical and
      surgical therapies, and risk factors for disease outcomes were analyzed. RESULTS:
      Chronic active or relapsing disease accounts for 44% of patients with late-onset
      UC. Across all age-groups, these disease patterns require 3-6 times more steroids
      than remitting disease, but immunomodulators and, to a lesser extent, biologics
      are less frequently prescribed in the elderly. Advanced age, concomitant diseases
      and related therapies were found to be inversely associated with the use of
      immunomodulators or biologics, but not with surgery. CONCLUSIONS: The conclusion
      that late-onset UC follows a mild course may apply only to a subset of patients.
      an important percentage of elderly patients present with more aggressive disease.
      Since steroid use and surgery rates did not differ in this subgroup, lower use of
      immunosuppressive therapy and biologics may reflect concerns in prescribing these
      therapies in the elderly.

PMID- 27717796
TI  - Localization of RR-1 and RR-2 cuticular proteins within the cuticle of Anopheles
      gambiae.
AB  - The largest arthropod cuticular protein family, CPR, has the Rebers and Riddiford
      (R&R) Consensus that in an extended form confers chitin-binding properties. Two
      forms of the Consensus, RR-1 and RR-2, have been recognized and initial data
      suggested that the RR-1 and RR-2 proteins were present in different regions
      within the cuticle itself. Thus, RR-2 proteins would contribute to exocuticle
      that becomes sclerotized, while RR-1s would be found in endocuticle that remains
      soft. An alternative, and more common, suggestion is that RR-1 proteins are used
      for soft, flexible cuticles such as intersegmental membranes, while RR-2s are
      associated with hard cuticle such as sclerites and head capsules. We used TEM
      immunogold detection to localize the position of several RR-1 and RR-2 proteins
      in the cuticle of Anopheles gambiae. RR-1s were localized in the procuticle of
      the soft intersegmental membrane except for one protein found in the endocuticle
      of hard cuticle. RR-2s were consistently found in hard cuticle and not in
      flexible cuticle. All RR-2 antibodies localized to the exocuticle and four out of
      six were also found in the endocuticle. Hence the location of RR-1s and RR-2s
      depends more on properties of individual proteins than on either hypothesis.

PMID- 27717797
TI  - Morphology and development of the accessory glands in various female cricket
      species.
AB  - The study presents new results with regard to the morphometric and
      ultrastructural development of the accessory glands in females of the three
      cricket species Gryllus bimaculatus, Gryllus assimilis, and Acheta domesticus.
      Furthermore, possible age-dependence of secretory productivity of single organs
      was analyzed by application of the ligature technique introduced in a previous
      contribution. Within the first 12 days of the adult phase, the accessory glands
      of all investigated cricket species exhibit a significant increase in length and
      width which assumes values between 50 and 100%. This gland growth is rather the
      result of a continuous increase in cellular volume and less that of mitotic cell
      propagation. In all species height and width of single gland cells increase by 60
      80% within the studied time interval. These changes in morphometry are commonly
      accompanied by ultrastructural modifications. Total glandular secretion is
      subject to an increase from the 5th to the 12th day of adult age. This
      development corresponds well with the number of eggs contemporaneously oviposited
      into the substrate and thus underlines the hypothesis, according to which the
      main function of the secretion consists in acting as a lubricant for the
      facilitated transport of the oocytes through the ovipositor.

PMID- 27717799
TI  - Reversed T Cell Receptor Docking on a Major Histocompatibility Class I Complex
      Limits Involvement in the Immune Response.
AB  - The anti-viral T cell response is drawn from the naive T cell repertoire. During
      influenza infection, the CD8+ T cell response to an H-2Db-restricted
      nucleoprotein epitope (NP366) is characterized by preferential expansion of T
      cells bearing TRBV13+ T cell receptors (TCRs) and avoidance of TRBV17+ T cells,
      despite the latter dominating the naive precursor repertoire. We found two
      TRBV17+ TCRs that bound H-2Db-NP366 with a 180 degrees  reversed polarity
      compared to the canonical TCR-pMHC-I docking. The TRBV17 beta-chain dominated the
      interaction and, whereas the complementarity determining region-3 (CDR3) loops
      exclusively mediated contacts with the MHC-I, peptide specificity was
      attributable to germline-encoded recognition. Nevertheless, the TRBV17+ TCR
      exhibited moderate affinity toward H-2Db-NP366 and was capable of signal
      transduction. Thus, the naive CD8+ T cell pool can comprise TCRs adopting
      reversed pMHC-I docking modes that limit their involvement in the immune
      response.

PMID- 27717798
TI  - Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide
      Induced Therapeutic Immunomodulatory Effects.
AB  - The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX)
      relies on intestinal bacteria. How and which relevant bacterial species are
      involved in tumor immunosurveillance, and their mechanism of action are unclear.
      Here, we identified two bacterial species, Enterococcus hirae and Barnesiella
      intestinihominis that are involved during CTX therapy. Whereas E. hirae
      translocated from the small intestine to secondary lymphoid organs and increased
      the intratumoral CD8/Treg ratio, B. intestinihominis accumulated in the colon and
      promoted the infiltration of IFN-gamma-producing gammadeltaT cells in cancer
      lesions. The immune sensor, NOD2, limited CTX-induced cancer immunosurveillance
      and the bioactivity of these microbes. Finally, E. hirae and B. intestinihominis
      specific-memory Th1 cell immune responses selectively predicted longer
      progression-free survival in advanced lung and ovarian cancer patients treated
      with chemo-immunotherapy. Altogether, E. hirae and B. intestinihominis represent
      valuable "oncomicrobiotics" ameliorating the efficacy of the most common
      alkylating immunomodulatory compound.

PMID- 27717800
TI  - Effect of iron deficiency anemia and iron supplementation on HbA1c levels -
      Implications for diagnosis of prediabetes and diabetes mellitus in Asian Indians.
AB  - BACKGROUND: We investigated the effect of iron deficiency anemia (IDA) on levels
      of glycated hemoglobin (HbA1c) and to compare its levels before and after iron
      supplementations. METHODS: Age and sex matched subjects were enrolled and
      clustered in 2 groups: IDA (n=62) and healthy controls (HC; n=60). HbA1c levels
      were estimated by HPLC. Hemogram were estimated by hematology analyser. Serum
      ferritin (ELISA) and other parameters of iron profile were measured by standard
      guidelines of ICSH. HbA1c values and iron studies were repeated after 3months of
      iron supplementation to determine the effect of iron therapy on HbA1c levels.
      RESULTS: Significantly higher HbA1c levels were observed in IDA subjects compared
      to HC (5.51+/-0.696 v/s 4.85+/-0.461%, p<0.001). A significant negative
      correlation was observed between HbA1c and hemoglobin, hematocrit, RBC count,
      MCH, MCHC and serum ferritin in IDA subjects (r=-0.632, -0.652, -0.384, -0.236, 
      0.192 and -0.441). Significant decline was noticed in HbA1c levels in IDA
      subjects after iron supplementation (5.51+/-0.696 before treatment v/s 5.044+/
      0.603 post-treatment; p<0.001). Post treatment, 70% subjects (14/20) with HbA1c
      in pre-diabetes range normalised to normal glucose tolerance (NGT) range and out
      of 6 patients with pre-treatment HbA1c in diabetes range, 5 reverted to pre
      diabetes range while 1 of them reverted to the NGT range. CONCLUSIONS: Caution
      must be exercised in interpreting the results of HbA1c in patients of IDA and
      iron deficiency must be corrected before diagnosing diabetes and pre-diabetes
      solely on the basis of HbA1c criteria.

PMID- 27717801
TI  - NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate
      production in bloodstream forms.
AB  - In the slender bloodstream form, Trypanosoma brucei mitochondria are repressed
      for many functions. Multiple components of mitochondrial complex I,
      NADH:ubiquinone oxidoreductase, are expressed in this stage, but electron
      transfer through complex I is not essential. Here we investigate the role of the
      parasite's second NADH:ubiquinone oxidoreductase, NDH2, which is composed of a
      single subunit that also localizes to the mitochondrion. While inducible
      knockdown of NDH2 had a modest growth effect in bloodstream forms, NDH2 null
      mutants, as well as inducible knockdowns in a complex I deficient background,
      showed a greater reduction in growth. Altering the NAD+/NADH balance would affect
      numerous processes directly and indirectly, including acetate production. Indeed,
      loss of NDH2 led to reduced levels of acetate, which is required for several
      essential pathways in bloodstream form T. brucei and which may have contributed
      to the observed growth defect. In conclusion our study shows that NDH2 is
      important, but not essential, in proliferating bloodstream forms of T. brucei,
      arguing that the mitochondrial NAD+/NADH balance is important in this stage, even
      though the mitochondrion itself is not actively engaged in the generation of ATP.

PMID- 27717802
TI  - Effects of patulin and ascladiol on porcine intestinal mucosa: An ex vivo
      approach.
AB  - Patulin (PAT) is a secondary metabolite mainly produced by Aspergillus and
      Penicillium that is frequently found contaminating apples and rotten fruits.
      Patulin can be transformed in potencially less toxic compounds such as ascladiol
      (ASC). Toxic effects of patulin were described in rats and in in vitro models,
      however concerning ascladiol, data are restricted to metabolic pathways. The aim
      of the present study was to evaluate the effects of different concentrations of
      PAT (10 MUM, 30 MUM, 100 MUM) and ASC (30 MUM, 100 MUM) on intestinal tissue
      using the jejunal explant model. Explants from pigs were exposed for 4 h to PAT
      and ASC and after this period were processed for histological, morphometrical and
      immunohistochemical analysis. Mild histological changes were observed in jejunal
      explants exposed to PAT and ASC, however no significant difference in the
      lesional score or villi height was observed between the PAT/ASC-groups and the
      control. Also, explants exposed to 100 MUM of PAT showed a significant decrease
      in goblet cells density and a significant increase in cell apoptosis. These
      results indicate that high levels of patulin can induce mild toxic effects on
      intestinal mucosa whereas ascladiol apparently is non-toxic to intestinal tissue.

PMID- 27717803
TI  - Marine fatty acids aggravate hepatotoxicity of alpha-HBCD in juvenile female
      BALB/c mice.
AB  - Oily fish, a source of long-chain omega-3 polyunsaturated fatty acids (LC n-3
      PUFAs), may contain persistent organic pollutants (POPs), including alpha
      hexabromocyclododecane (alpha-HBCD). In experimental studies, marine LC n-3 PUFAs
      ameliorate fatty liver development while HBCD exposure was found to cause liver
      fatty acid (FA) changes. The present study investigated interactions of FAs and
      alpha-HBCD in juvenile female BALB/c mice using a factorial design. Mice (n = 48)
      were exposed for 28 days to a low (100 MUg*kg body weight (BW)-1*day-1) or high
      dose (100 mg*kg BW-1*day-1) of alpha-HBCD in diets with or without LC n-3 PUFAs.
      High dose alpha-HBCD affected whole body lipid metabolism leading to changes in
      body weight and composition, and pathological changes in hepatic histology, which
      surprisingly were aggravated by dietary LC n-3 PUFAs. Hepatic FA profiling and
      gene expression analysis indicated that the dietary modulation of the hepatotoxic
      response to the high dose of alpha-HBCD was associated with differential effects
      on FA beta-oxidation. Our results suggest that in a juvenile mouse model, marine
      FAs accentuate hepatotoxic effects of high dose alpha-HBCD. This highlights that
      the background diet is a critical variable in the risk assessment of POPs and
      warrants further investigation of dietary mediated toxicity of food contaminants.

PMID- 27717804
TI  - Seasonal dynamics of the phytochemical constituents and bioactivities of extracts
      from Stenoloma chusanum (L.) Ching.
AB  - Stenoloma chusanum is a traditional Chinese medicinal herb with a very high total
      flavonoid content (TFC). The seasonal dynamics of the TFC and total phenolic
      content (TPC) in S. chusanum, as well as antioxidant activity, were investigated.
      The TFC and TPC showed clear seasonal dynamics, reaching their maxima (24.63 +/-
      1.34% and 9.58 +/- 0.41%, respectively) in February. The TFC and TPC in the
      aerial parts of the plant were much higher than those in the subterranean parts;
      however, the antioxidant activities of the extracts from the subterranean parts
      were slightly higher than those from the aerial parts. Moreover, the extracts
      exhibited higher inhibition against tyrosinase than against arbutin (the positive
      control). The extract from S. chusanum collected in February was associated with
      the highest proliferation and apoptosis of K562 cells. The phytochemicals in the
      extract were analyzed using LC-MS, and were found to comprise of 12 flavonoids,
      five alkaloids, one sesquiterpenoid and one phenypropanoid. In conclusion, S.
      chusanum exhibits multiple bioactivities; these results could contribute to the
      therapeutic application of the plants in indigenous medicine.

PMID- 27717805
TI  - The Na+/HCO3- co-transporter is protective during ischemia in astrocytes.
AB  - The sodium bicarbonate co-transporter (NBC) is the major bicarbonate-dependent
      acid-base transporter in mammalian astrocytes and has been implicated in ischemic
      brain injury. A malfunction of astrocytes could have great impact on the outcome
      of stroke due to their participation in the formation of blood-brain barrier,
      synaptic transmission, and electrolyte balance in the human brain. Nevertheless,
      the role of NBC in the ischemic astrocyte death has not been well understood. In
      this work, we obtained skin biopsies from healthy human subjects and had their
      fibroblasts grown in culture and reprogrammed into human-induced pluripotent stem
      cells (hiPSCs). These hiPSCs were further differentiated into neuroprogenitor
      cells (NPCs) and then into human astrocytes. These astrocytes express GFAP and
      S100beta and readily propagate calcium waves upon mechanical stimulation. Using
      pH-sensitive dye BCECF [2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein]
      and qPCR technique, we have confirmed that these astrocytes express functional
      NBC including electrogenic NBC (NBCe). In addition, astrocytes exposed to an
      ischemic solution (IS) that mimics the ischemic penumbral environment enhanced
      both mRNA and protein expression level of NBCe1 in astrocytes. Using IS and a
      generic NBC blocker S0859, we have studied the involvement of NBC in IS-induced
      human astrocytes death. Our results show that a 30MUM S0859 induced a 97.5+/-1.6%
      (n=10) cell death in IS-treated astrocytes, which is significantly higher than
      43.6+/-4.5%, (n=10) in the control group treated with IS alone. In summary, a NBC
      blocker exaggerates IS-induced cell death, suggesting that NBC activity is
      essential for astrocyte survival when exposed to ischemic penumbral environment.

PMID- 27717806
TI  - Convergent transcriptomics and proteomics of environmental enrichment and cocaine
      identifies novel therapeutic strategies for addiction.
AB  - Transcriptomic and proteomic approaches have separately proven effective at
      identifying novel mechanisms affecting addiction-related behavior; however, it is
      difficult to prioritize the many promising leads from each approach. A convergent
      secondary analysis of proteomic and transcriptomic results can glean additional
      information to help prioritize promising leads. The current study is a secondary
      analysis of the convergence of recently published separate transcriptomic and
      proteomic analyses of nucleus accumbens (NAc) tissue from rats subjected to
      environmental enrichment vs. isolation and cocaine self-administration vs.
      saline. Multiple bioinformatics approaches (e.g. Gene Ontology (GO) analysis,
      Ingenuity Pathway Analysis (IPA), and Gene Set Enrichment Analysis (GSEA)) were
      used to interrogate these rich data sets. Although there was little
      correspondence between mRNA vs. protein at the individual target level, good
      correspondence was found at the level of gene/protein sets, particularly for the
      environmental enrichment manipulation. These data identify gene sets where there
      is a positive relationship between changes in mRNA and protein (e.g. glycolysis,
      ATP synthesis, translation elongation factor activity, etc.) and gene sets where
      there is an inverse relationship (e.g. ribosomes, Rho GTPase signaling, protein
      ubiquitination, etc.). Overall environmental enrichment produced better
      correspondence than cocaine self-administration. The individual targets
      contributing to mRNA and protein effects were largely not overlapping. As a
      whole, these results confirm that robust transcriptomic and proteomic data sets
      can provide similar results at the gene/protein set level even when there is
      little correspondence at the individual target level and little overlap in the
      targets contributing to the effects.

PMID- 27717808
TI  - Alterations in AMPA receptor subunit expression in cortical inhibitory
      interneurons in the epileptic stargazer mutant mouse.
AB  - Absence seizures arise from disturbances within the corticothalamocortical
      network, however the precise cellular and molecular mechanisms underlying seizure
      generation arising from different genetic backgrounds are not fully understood.
      While recent experimental evidence suggests that changes in inhibitory
      microcircuits in the cortex may contribute to generation of the hallmark spike
      wave discharges, it is still unclear if altered cortical inhibition is a result
      of interneuron dysfunction due to compromised glutamatergic excitation and/or
      changes in cortical interneuron number. The stargazer mouse model of absence
      epilepsy presents with a genetic deficit in stargazin, which is predominantly
      expressed in cortical parvalbumin-positive (PV+) interneurons, and involved in
      the trafficking of glutamatergic AMPA receptors. Hence, in this study we examine
      changes in (1) the subunit-specific expression of AMPA receptors which could
      potentially result in a loss of excitation onto cortical PV+ interneurons, and
      (2) PV+ neuron density that could additionally impair cortical inhibition. Using
      Western blot analysis we found subunit-specific alterations in AMPA receptor
      expression in the stargazer somatosensory cortex. Further analysis using confocal
      fluorescence microscopy revealed that although there are no changes in cortical
      PV+ interneuron number, there is a predominant loss of GluA1 and 4 containing
      AMPA receptors in PV+ neurons in stargazers compared to non-epileptic controls.
      Taken together, these data suggest that the loss of AMPA receptors in PV+ neurons
      could impair their feed-forward inhibitory output, ultimately altering cortical
      network oscillations, and contribute to seizure generation in stargazers. As such
      the feed-forward inhibitory interneurons could be potential targets for future
      therapeutic intervention for some absence epilepsy patients.

PMID- 27717809
TI  - Dysregulation of the endocannabinoid signaling system in the cerebellum and
      brainstem in a transgenic mouse model of spinocerebellar ataxia type-3.
AB  - Spinocerebellar ataxia type-3 (SCA-3) is a rare disease but it is the most
      frequent type within the autosomal dominant inherited ataxias. The disease lacks
      an effective treatment to alleviate major symptoms and to modify disease
      progression. Our recent findings that endocannabinoid receptors and enzymes are
      significantly altered in the post-mortem cerebellum of patients affected by
      autosomal-dominant hereditary ataxias suggest that targeting the endocannabinoid
      signaling system may be a promising therapeutic option. Our goal was to
      investigate the status of the endocannabinoid signaling system in a transgenic
      mouse model of SCA-3, in the two CNS structures most affected in this disease -
      cerebellum and brainstem. These animals exhibited progressive motor
      incoordination, imbalance, abnormal gait, muscle weakness, and dystonia, in
      parallel to reduced in vivo brain glucose metabolism, deterioration of specific
      neuron subsets located in the dentate nucleus and pontine nuclei, small changes
      in microglial morphology, and reduction in glial glutamate transporters.
      Concerning the endocannabinoid signaling, our data indicated no changes in CB2
      receptors. By contrast, CB1 receptors increased in the Purkinje cell layer, in
      particular in terminals of basket cells, but they were reduced in the dentate
      nucleus. We also measured the levels of endocannabinoid lipids and found
      reductions in anandamide and oleoylethanolamide in the brainstem. These changes
      correlated with an increase in the FAAH enzyme in the brainstem, which also
      occurred in some cerebellar areas, whereas other endocannabinoid-related enzymes
      were not altered. Collectively, our results in SCA-3 mutant mice confirm a
      possible dysregulation in the endocannabinoid system in the most important brain
      structures affected in this type of ataxia, suggesting that a pharmacological
      manipulation addressed to correct these changes could be a promising option in
      SCA-3.

PMID- 27717807
TI  - Sex differences in astrocyte and microglia responses immediately following middle
      cerebral artery occlusion in adult mice.
AB  - Epidemiological studies report that infarct size is decreased and stroke outcomes
      are improved in young females when compared to males. However, mechanistic
      insight is lacking. We posit that sex-specific differences in glial cell
      functions occurring immediately after ischemic stroke are a source of dichotomous
      outcomes. In this study we assessed astrocyte Ca2+ dynamics, aquaporin 4 (AQP4)
      polarity, S100beta expression pattern, as well as, microglia morphology and
      phagocytic marker CD11b in male and female mice following 60min of middle
      cerebral artery (MCA) occlusion. We reveal sex differences in the frequency of
      intracellular astrocyte Ca2+ elevations (F(1,86)=8.19, P=0.005) and microglia
      volume (F(1,40)=12.47, P=0.009) immediately following MCA occlusion in acute
      brain slices. Measured in fixed tissue, AQP4 polarity was disrupted
      (F(5,86)=3.30, P=0.009) and the area of non-S100beta immunoreactivity increased
      in ipsilateral brain regions after 60min of MCA occlusion (F(5,86)=4.72,
      P=0.007). However, astrocyte changes were robust in male mice when compared to
      females. Additional sex differences were discovered regarding microglia
      phagocytic receptor CD11b. In sham mice, constitutively high CD11b
      immunofluorescence was observed in females when compared to males (P=0.03). When
      compared to sham, only male mice exhibited an increase in CD11b immunoreactivity
      after MCA occlusion (P=0.006). We posit that a sex difference in the presence of
      constitutive CD11b has a role in determining male and female microglia phagocytic
      responses to ischemia. Taken together, these findings are critical to
      understanding potential sex differences in glial physiology as well as stroke
      pathobiology which are foundational for the development of future sex-specific
      stroke therapies.

PMID- 27717810
TI  - Activation of state-regulating neurochemical systems in newborn and embryonic
      chicks.
AB  - Coordinated activity in different sets of widely-projecting neurochemical systems
      characterize waking (W) and sleep (S). How and when this coordination is achieved
      during development is not known. We used embryos and newborns of a precocial bird
      species (chickens) to assess developmental activation in different neurochemical
      systems using cFos expression, which has been extensively employed to examine
      cellular activation during S and W in adult mammals. Similarly to adult mammals,
      newborn awake chicks showed significantly higher cFos expression in W-active
      hypocretin/orexin (H/O), serotonergic Dorsal Raphe, noradrenergic Locus Coeruleus
      and cholinergic Laterodorsal and Pedunculopontine Tegmental (Ch-LDT/PT) neurons
      when compared to sleeping chicks. cFos expression was significantly correlated
      both between these systems, and with the amount of W. S-active melanin
      concentrating hormone (MCH) neurons showed very low cFos expression with no
      difference between sleeping and awake chicks, possibly due to the very short
      duration of S episodes. In embryonic chicks, cFos expression was low or absent
      across all five systems at embryonic day (E) 12. Unexpectedly, a strong
      activation was seen at E16 in H/O neurons. The highest activation of Ch-LDT/PT
      (also S-active) and MCH neurons was seen at E20. These data suggest that
      maturation of arousal systems is achieved soon after hatching, while S-control
      networks are active in late chick embryos.

PMID- 27717811
TI  - Structure and functions of the chaperone-like p97/CDC48 in plants.
AB  - BACKGROUND: The chaperone-like p97 is a member of the AAA+ ATPase enzyme family
      that contributes to numerous cellular activities. P97 has been broadly studied in
      mammals (VCP/p97) and yeasts (CDC48: Cell Division Cycle 48/p97) and numerous
      investigations highlighted that this protein is post-translationally regulated,
      is structured in homohexamer and interacts with partners and cofactors that
      direct it to distinct cellular signalization pathway including protein quality
      control and degradation, cell cycle regulation, genome stability, vesicular
      trafficking, autophagy and immunity. SCOPE OF REVIEW: p97 is also conserved in
      plants (CDC48) but its functions are less understood. In the present review we
      intended to present the state of the art of the structure, regulation and
      functions of CDC48 in plants. MAJOR CONCLUSIONS: Evidence accumulated underline
      that CDC48 plays a crucial role in development, cell cycle regulation and protein
      turnover in plants. Furthermore, its involvement in plant immunity has recently
      emerged and first interacting partners have been identified, shedding light on
      its putative cellular activities. GENERAL SIGNIFICANCE: Identification of
      emerging functions of CDC48 in plants opens new roads of research in immunity and
      provides new insights into the mechanisms of protein quality control.

PMID- 27717812
TI  - Behavioural endophenotypes in mice lacking the auxiliary GABAB receptor subunit
      KCTD16.
AB  - Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the
      brain and is implicated in the pathophysiology of a number of neuropsychiatric
      disorders. The GABAB receptors are G-protein coupled receptors consisting of
      principle subunits and auxiliary potassium channel tetramerization domain (KCTD)
      subunits. The KCTD subunits 8, 12, 12b and 16 are cytosolic proteins that
      determine the kinetics of the GABAB receptor response. Previously, we
      demonstrated that Kctd12 null mutant mice (Kctd12-/-) exhibit increased auditory
      fear learning and that Kctd12+/- mice show altered circadian activity, as well as
      increased intrinsic excitability in hippocampal pyramidal neurons. KCTD16 has
      been demonstrated to influence neuronal excitability by regulating GABAB receptor
      mediated gating of postsynaptic ion channels. In the present study we
      investigated for behavioural endophenotypes in Kctd16-/- and Kctd16+/- mice.
      Compared with wild-type (WT) littermates, auditory and contextual fear
      conditioning were normal in both Kctd16-/- and Kctd16+/- mice. When fear memory
      was tested on the following day, Kctd16-/- mice exhibited less extinction of
      auditory fear memory relative to WT and Kctd16+/- mice, as well as more
      contextual fear memory relative to WT and, in particular, Kctd16+/- mice.
      Relative to WT, both Kctd16+/- and Kctd16-/- mice exhibited normal circadian
      activity. This study adds to the evidence that auxillary KCTD subunits of GABAB
      receptors contribute to the regulation of behaviours that could constitute
      endophenotypes for hyper-reactivity to aversive stimuli in neuropsychiatric
      disorders.

PMID- 27717814
TI  - Differential associations between behavioral and cortisol responses to a stressor
      in securely versus insecurely attached infants.
AB  - In this study we examined whether securely versus insecurely attached infants use
      different regulatory behaviors in absence of their mother and whether these
      regulatory behaviors are differentially associated with physiological stress
      responses in secure versus insecure infants. Participants were 193 one-year-olds
      and their mothers. During three 3-min episodes of separation from the mother in
      the Strange Situation Procedure (SSP) [1], the following infant regulatory
      behaviors were observed: crying, fussing, self-soothing, manipulation of toys,
      and manipulation of the door. Salivary cortisol was measured at baseline and 25,
      40, and 60min after the SSP to measure reactivity and recovery. Additionally,
      infants were classified as securely or insecurely attached to their mothers.
      During the mother's absence, secure infants engaged more in manipulation of the
      door than insecure infants. Furthermore, in insecure (but not secure) infants
      less fussing was associated with higher cortisol reactivity, while in secure (but
      not insecure) infants more self-soothing was associated with higher cortisol
      reactivity. In total, 29% of the variance in cortisol reactivity was explained by
      infant regulatory behaviors in the mother's absence. Cortisol recovery was not
      predicted by infant regulatory behaviors in the mother's absence. To conclude,
      the results show differential associations between behavioral and cortisol
      responses to a stressor in secure versus insecure infants. This might indicate
      that secure and insecure infants apply different behavioral regulatory strategies
      when physiologically stressed.

PMID- 27717813
TI  - Human adipose-derived stem cells ameliorate repetitive behavior, social deficit
      and anxiety in a VPA-induced autism mouse model.
AB  - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder
      characterized by impairments in social interaction and communication, and
      patients often display co-occurring repetitive behaviors. Although the global
      prevalence of ASD has increased over time, the etiology and treatments for ASD
      are poorly understood. Recently, some researchers have suggested that stem cells
      have therapeutic potential for ASD. Thus, in the present study, we investigated
      the therapeutic effects of human adipose-derived stem cells (hASCs), a kind of
      autologous mesenchymal stem cells (MSCs) isolated from adipose tissue, on
      valproic acid (VPA)-induced autism model mice. Human ASCs were injected into the
      neonatal pups (P2 or P3) intraventricularly and then we evaluated major behavior
      symptoms of ASD. VPA-treated mice showed increased repetitive behaviors,
      decreased social interactions and increased anxiety but these autistic behaviors
      were ameliorated through transplantation of hASCs. In addition, hASCs
      transplantation restored the alteration of phosphatase and tensin homolog (PTEN)
      expression and p-AKT/AKT ratio in the brains of VPA-induced ASD model mice. The
      decreased level of vascular endothelial growth factor (VEGF) and interleukin 10
      (IL-10) by VPA were rescued in the brains of the hASC-injected VPA mice. With
      these results, we experimentally found hASCs' therapeutic effects on autistic
      phenotypes in a ASD model mice for the first time. This animal model system can
      be used to elucidate further mechanisms of therapeutic effects of hASCs in ASD.

PMID- 27717815
TI  - Reorganization of motor cortex and impairment of motor performance induced by
      hindlimb unloading are partially reversed by cortical IGF-1 administration.
AB  - Immobilization, bed rest, or sedentary lifestyle, are known to induce a profound
      impairment in sensorimotor performance. These alterations are due to a
      combination of peripheral and central factors. Previous data conducted on a rat
      model of disuse (hindlimb unloading, HU) have shown a profound reorganization of
      motor cortex and an impairment of motor performance. Recently, our interest was
      turned towards the role of insulin-like growth factor 1 (IGF-1) in cerebral
      plasticity since this growth factor is considered as the mediator of beneficial
      effects of exercise on the central nervous system, and its cortical level is
      decreased after a 14-day period of HU. In the present study, we attempted to
      determine whether a chronic subdural administration of IGF-1 in HU rats could
      prevent deleterious effects of HU on the motor cortex and on motor activity. We
      demonstrated that HU induces a shrinkage of hindlimb cortical representation and
      an increase in current threshold to elicit a movement. Administration of IGF-1 in
      HU rats partially reversed these changes. The functional evaluation revealed that
      IGF-1 prevents the decrease in spontaneous activity found in HU rats and the
      changes in hip kinematics during overground locomotion, but had no effect of
      challenged locomotion (ladder rung walking test). Taken together, these data
      clearly indicate the implication of IGF-1 in cortical plastic mechanisms and in
      behavioral alteration induced by a decreased in sensorimotor activity.

PMID- 27717816
TI  - Extending the Arc of Rotation of the Pectoralis Major Myocutaneous Flap for
      Orofacial Reconstruction via a Modified Subclavicular Route Through the
      Clavipectoral Fascia.
AB  - PURPOSE: Drawbacks of the conventional supraclavicular overlay of the pectoralis
      major myocutaneous flap (PMMF) include the resultant unesthetic cervical bulge
      and the limited cephalad extension that limits its use to mandibular or cervical
      defects. This study discusses the technique and comparative advantages of a more
      esthetic subclavicular route through the clavipectoral fascia that allows an
      increased arc of rotation to reconstruct orofacial defects. MATERIALS AND
      METHODS: Patients with orofacial defects that were reconstructed with a PMMF
      through the modified subclavicular route were included in this retrospective
      cohort study, which aimed to compare the gain in extension accorded through the
      modified subclavicular tunnel over an initial conventional supraclavicular
      overlay. Outcome variables included the dimension of each skin paddle and the
      cross-sectional area of each flap. Other variables, such as age and gender, also
      were investigated. Complications that arose from this technique were
      statistically compared with these variables and with those from previously
      reported studies. All data analyses were performed using Pearson chi2 and
      correlation tests. RESULTS: Twelve patients (7 women and 5 men) who underwent a
      primary reconstruction with the PMMF during a 1-year period from November 2010 to
      November 2011 were selected for this study. All 12 flaps survived; 3 developed
      minor postoperative complications that resolved within the 3-month review period.
      A PMMF with an average dimension of 12.75 * 6.0 * 3.725 cm and cross-sectional
      area of 20.65 cm2 could pass through this modified tunnel, achieving an average
      gain in extension of 3.2 cm that enabled the reconstruction of defects up to and
      above the level of the oral commissure. Apart from skin paddle dimension, all
      other variables were not found to be statistically related to the extension
      accorded by the modified route. Complications that occurred appeared to be
      related only to the cross-sectional area of the flap. CONCLUSION: The increased
      cephalad extension afforded by this modified subclavicular route through the
      clavipectoral fascia permitted the reconstruction of orofacial defects that would
      otherwise have required free vascularized grafts with microvascular surgery and
      avoided the unesthetic cervical bulge from conventional supraclavicular overlays
      of the PMMF.

PMID- 27717817
TI  - An Overview of Infections Associated With Soft Tissue Facial Fillers:
      Identification, Prevention, and Treatment.
AB  - PURPOSE: The purpose of this study was to provide an overview of infections
      associated with facial soft tissue fillers. MATERIALS AND METHODS: A literature
      review was performed which evaluated infections associated with facial soft
      tissue fillers. RESULTS: Infection rates with soft tissue fillers are low and are
      estimated at 0.04 to 0.2%. Most of these infections arise when skin contaminants
      infiltrate the injection site at the time of injection. These infections can
      occur early, up to several days after treatment, or delayed, occurring weeks to
      years after treatment. Reactions vary based on the filler absorbability and
      duration. Early recognition and treatment are important factors in managing our
      cosmetic surgery patients. CONCLUSION: Although facial fillers are safe and
      predictable, infections can still occur. Oral and maxillofacial surgeons need to
      be able to prevent, recognize, and properly manage infections related to these
      popular injections.

PMID- 27717819
TI  - Concomitant Suppurative Parotitis and Condylar Osteomyelitis.
AB  - Parotitis is a common occurrence in the immunocompromised, dehydrated, and
      malnourished patient as a result of dysfunctional ductal and parotid cells.
      Inflammation can be acute or chronic based on clinical history, and it can be
      suppurative based on the presence of micro or macro abscess formation within the
      substance of the gland. This report presents a case of concomitant condylar
      osteomyelitis and chronic suppurative parotitis in the setting of previous
      methicillin-susceptible Staphylococcus aureus foot infection. Ultimately,
      resection of osteomyelitis, drainage of parotid infection, and intravenous
      antibiotic therapy led to full resolution of the infection and symptoms. The
      final pathology of osteomyelitis of the temporomandibular joint and methicillin
      resistant S aureus infection is an unusual consequence of chronic parotitis. The
      patient was restored with a total joint replacement approximately 3 months after
      resection with no recurrence of infection after 24 months.

PMID- 27717818
TI  - Craniofacial Resection and Reconstruction in Patients With Recurrent Cancer
      Involving the Craniomaxillofacial Region.
AB  - PURPOSE: Head and neck tumors that involve the craniomaxillofacial region are
      classified as stage IVb disease and are clinically challenging. In this study,
      the outcomes of craniofacial resection and craniofacial reconstruction in
      patients with recurrent malignant tumors involving the craniomaxillofacial region
      were evaluated. PATIENTS AND METHODS: This retrospective observational study was
      conducted from January 2008 to August 2015. Data collected for each patient
      included age, gender, tumor site, initial treatment, craniofacial resection,
      reconstruction flaps and complications after craniofacial resection, adjuvant
      treatment, and reported outcomes of craniofacial resection and craniofacial
      reconstruction. The chi2 test in SPSS was used to analyze the data. RESULTS:
      Twenty-four patients with recurrent malignant tumors involving the
      craniomaxillofacial region were identified who had undergone craniofacial
      resection at the Center of Craniomaxillofacial Surgery of Sun Yat-sen University
      (Guangzhou, Guangdong, China). The study population was comprised of 24 patients
      (15 men and 9 women; age range, 21 to 73 yr) with recurrent tumors (58.3% with
      squamous cell carcinoma [SCC], 41.7% with sarcoma [SA]) involving the
      craniomaxillofacial region who underwent craniofacial resection. Craniofacial
      resection consisted of orbital exenteration and maxillotomy; anterior skull base
      surgery, facial resection, and mandibulotomy; or ipsilateral radical neck
      dissection. The resultant craniomaxillofacial defects were reconstructed using
      extended vertical lower trapezius island myocutaneous flaps (TIMFs), temporalis
      myofascial flaps, or submental flaps. All patients with recurrent malignant tumor
      involving the craniomaxillofacial region underwent gross total resection of the
      tumor; 22 patients underwent craniofacial reconstruction. There were no major
      surgical complications. Minor flap failure and wound dehiscence in the donor site
      occurred in 4 patients. The follow-up period ranged from 8 to 36 months. Seven
      patients in the SCC group and 7 in the SA group were alive with no evidence of
      disease (AND), 3 in the SCC group and 2 in the SA group were alive with disease
      (AWD), and 4 in the SCC and 1 in the SA group died of the disease (DOD) after
      local recurrence or distant metastases at 8 to 18 months. There were no
      statistical differences among the AND, AWD, and DOD groups. CONCLUSIONS:
      Craniofacial resection remains an effective salvage treatment for patients with
      recurrent SCC and SA involving the craniomaxillofacial region. The extended
      vertical lower TIMF is a large, simple, and reliable flap for reconstructing
      major defects after a craniofacial resection.

PMID- 27717820
TI  - Discovery of an artificial peptide agonist to the fibroblast growth factor
      receptor 1c/betaKlotho complex from random peptide T7 phage display.
AB  - Fibroblast growth factor receptor-1c (FGFR1c)/betaKlotho (KLB) complex is a
      receptor of fibroblast growth factor 21 (FGF21). Pharmacologically, FGF21 shows
      anti-obesity and anti-diabetic effects upon peripheral administration. Here, we
      report the development of an artificial peptide agonist to the FGFR1c/KLB
      heterodimer complex. The peptide, F91-8A07 (LPGRTCREYPDLWWVRCY), was discovered
      from random peptide T7 phage display and selectively bound to the FGFR1c/KLB
      complex, but not to FGFR1c and KLB individually. After subsequent peptide
      dimerization using a short polyethyleneglycol (PEG) linker, the dimeric F91-8A07
      peptide showed higher potent agonist activity than that of FGF21 in cultured
      primary human adipocytes. Moreover, the dimeric peptide led to an expression of
      the early growth response protein-1 (Egr-1) mRNA in vivo, which is a target gene
      of FGFR1c. To the best of our knowledge, this is the first report of a FGFR1c/KLB
      complex-selective artificial peptide agonist.

PMID- 27717821
TI  - miR-144-3p serves as a tumor suppressor for renal cell carcinoma and inhibits its
      invasion and metastasis by targeting MAP3K8.
AB  - MicroRNAs (miRNAs) are important regulators involved in various cancers,
      including renal cell carcinoma (RCC). The role of the miRNAs involved in RCC
      progress and metastasis is largely unknown. Here, miRNA microarray analysis was
      performed to screen the significant miRNAs involved in RCC progress, and miR-144
      3p was chosen for further study. We found that the expression of miR-144-3p was
      significantly lower in RCC specimens and cell lines. In addition, low expression
      level of miR-144-3p is correlated with tumor progression and poor survival in RCC
      patients. Based on in vitro assays, we found that miR-144-3p significantly
      inhibit cancer cell proliferation and progression. Furthermore, function studies
      revealed that miR-144-3p was significantly correlated with the metastasis
      potential by affecting the epithelial-mesenchymal transition (EMT). Moreover,
      Mitogen-activated protein kinase 8 (MAP3K8) is direct target of miR-144-3p, while
      the expression levels of MAP3K8 were inversely correlated with the expression
      levels of miR-144-3p in RCC tissues. Overall, our findings demonstrate that miR
      144-3p targeted the MAP3K8 pathway to reduce tumor cells proliferation and
      metastasis in RCC, suggesting that this axis may provide a novel therapeutic
      target for RCC therapy.

PMID- 27717822
TI  - Inhibiting c-Jun N-terminal kinase partially attenuates caffeine-dependent cell
      death without alleviating the caffeine-induced reduction in mitochondrial
      respiration in C2C12 skeletal myotubes.
AB  - Caffeine is a widely consumed stimulant that has previously been shown to promote
      cytotoxic stress and even cell death in numerous mammalian cell lines. Thus far
      there is little information available regarding the toxicity of caffeine in
      skeletal muscle cells. Our preliminary data revealed that treating C2C12 myotubes
      with 5 mM caffeine for 6 h increased nuclear fragmentation and reduced basal and
      maximal oxygen consumption rate (OCR) in skeletal myotubes. The purpose of this
      study was to further elucidate the pathways by which caffeine increased cell
      death and reduced mitochondrial respiration. We specifically examined the role of
      c-Jun N-terminal kinase (JNK), which has previously been shown to simultaneously
      increase caspase-dependent cell death and reduce mitochondrial respiration in
      other mammalian cell lines. We found that caffeine promoted a dose-dependent
      increase in cell death in multinucleated myotubes but did not in mononucleated
      myoblasts. The addition of 10 MUM Z-DEVD-FMK, a specific inhibitor of executioner
      caspases, completely inhibited caffeine-dependent cell death. Further, the
      addition of 400 MUM dantrolene, a specific ryanodine receptor (RYR) inhibitor,
      prevented the caffeine-dependent increase in cell death and the reduction in
      basal and maximal OCR. We also discovered that caffeine treatment significantly
      increased the phosphorylation of JNK and that the addition of 30 MUM SP600125
      (JNKi), a specific JNK inhibitor, partially attenuated caffeine-induced cell
      death without preventing the caffeine-dependent reduction in basal and maximal
      OCR. Our results suggest that JNK partially mediates the increase in caspase
      dependent cell death but does not contribute to reduced mitochondrial respiration
      in caffeine-treated skeletal muscle cells. We conclude that caffeine increased
      cell death and reduced mitochondrial respiration in a calcium-dependent manner by
      activating the RYR and promoting reticular calcium release.

PMID- 27717823
TI  - Plexin A1 signaling confers malignant phenotypes in lung cancer cells.
AB  - Aberrant changes to several signaling pathways because of genetic mutations or
      increased cytokine production are critical for tumor cells to become malignant.
      Semaphorin 3A (SEMA3A) acts as a bivalent factor that suppresses or promotes
      tumor development in different pathological backgrounds. Previously, we showed
      that SEMA3A positively regulated the proliferative and glycolytic activities of
      mouse-derived Lewis lung carcinoma (LLC) cells. Plexins A1-A4 (PLXNA1-PLXNA4) are
      SEMA3A receptors; however, it is not known which subtype is critical for
      oncogenic SEMA3A signaling. We used LLC cells to investigate the role of PLXNA1
      in oncogenic SEMA3A signaling. Using short hairpin RNA-mediated knockdown, we
      investigated the effects of constitutive inhibition of Plxna1 on cell
      proliferation, metabolic dependency, and epidermal growth factor receptor
      tyrosine kinase inhibitor (EGFR-TKI) sensitivity. We found that Plxna1 knockdown
      did not affect apoptosis but resulted in decreased cell proliferation and
      reductions in mRNA expression levels of proliferation-marker genes, such as
      Ccnd1, Pcna, and Myc. In addition, we found decreased mRNA expression levels of
      glycolysis-associated genes, such as Pkm2 and Ldha, and decreased lactate
      production. In contrast, we found no changes in the mRNA expression levels of
      oxidative phosphorylation-associated genes, such as Cycs, Cox5a, and Atp5g1. We
      found that Plxna1 knockdown conferred resistance to glucose starvation but
      increased cytotoxicity to oligomycin. Plxna1 or Sema3a knockdown caused an
      increased sensitivity to the EGFR-TKIs gefitinib and erlotinib, in Lewis lung
      carcinoma (LLC) cells. These findings demonstrate that PLXNA1 mediates the
      acquisition of malignant phenotypes induced by autocrine SEMA3A signaling.

PMID- 27717825
TI  - alphaMSH promotes preadipocyte proliferation by alleviating ER stress-induced
      leptin resistance and by activating Notch1 signal in mice.
AB  - Alpha-melanocyte stimulating hormone (alphaMSH) has an important role in the
      regulation of body weight and energy expenditure. Nevertheless, the molecular
      mechanisms of circulating alphaMSH on preadipocyte proliferation remain elusive.
      We found alphaMSH was reduced by high fat diet (HFD) while leptin was elevated in
      adipose tissue. Leptin resistance and endoplasmic reticulum (ER) stress of
      adipose tissue were increased in obese mice. alphaMSH increased leptin
      sensitivity and alleviated ER stress along with increased p-STAT3 level and
      reduced SOCS3, GRP78, CHOP, ATF4, p27 and p53 levels. alphaMSH and leptin co
      treatment alleviated ER stress through decreasing the levels of GRP78 and CHOP.
      Tunicamycin (TM) or thapsigargin (Tg) induced ER stress blunted leptin
      sensitivity and inhibited preadipocyte proliferation. alphaMSH and leptin co
      treatment increased the cell number, augmented G1-S transition, elevated leptin
      sensitivity, and reduced ER stress; it also activated Notch1 signal and
      stimulated preadipocyte proliferation, whereas ER stress marker genes were
      decreased during this process. However, the effects of alphaMSH and leptin were
      blocked by the specific inhibitor of Notch1 signal. In summary, our data revealed
      alphaMSH enhanced leptin sensitivity and preadipocyte proliferation, meanwhile
      inhibited ER stress of preadipocytes by activating Notch1 signal.

PMID- 27717824
TI  - MyD88 contributes to neuroinflammatory responses induced by cerebral
      ischemia/reperfusion in mice.
AB  - Myeloid differentiation primary-response protein-88 (MyD88) is one of adaptor
      proteins mediating Toll-like receptors (TLRs) signaling. Activation of MyD88
      results in the activation of nuclear factor kappa B (NFkappaB) and the increase
      of inflammatory responses. Evidences have demonstrated that TLRs signaling
      contributes to cerebral ischemia/reperfusion (I/R) injury. However, the role of
      MyD88 in this mechanism of action is disputed and needs to be clarified. In the
      present study, in a mouse model of cerebral I/R, we examined the activities of
      NFkappaB and interferon factor-3 (IRF3), and the inflammatory responses in
      ischemic brain tissue using ELISA, Western blots, and real-time PCR. Neurological
      function and cerebral infarct size were also evaluated 24 h after cerebral I/R.
      Our results showed that NFkappaB activity increased in ischemic brains, but IRF3
      was not activated after cerebral I/R, in wild-type (WT) mice. MyD88 deficit
      inhibited the activation of NFkappaB, and the expression of interleukin-1beta (IL
      1beta), IL-6, Beclin-1 (BECN1), pellino-1, and cyclooxygenase-2 (COX-2) increased
      by cerebral I/R compared with WT mice. Interestingly, the expression of
      interferon Beta 1 (INFB1) and vascular endothelial growth factor (VEGF) increased
      in MyD88 KO mice. Unexpectedly, although the neurological function improved in
      the MyD88 knockout (KO) mice, the deficit of MyD88 failed to reduce cerebral
      infarct size compared to WT mice. We concluded that MyD88-dependent signaling
      contributes to the inflammatory responses induced by cerebral I/R. MyD88 deficit
      may inhibit the increased inflammatory response and increase neuroprotective
      signaling.

PMID- 27717826
TI  - Treadmill exercise induces selective changes in hippocampal histone acetylation
      during the aging process in rats.
AB  - Physical exercise and the aging process have been shown to induce opposite
      effects on epigenetic marks, such as histone acetylation. The impact of exercise
      on hippocampal histone acetylation on specific lysine residues, especially during
      the aging process, is rarely studied. The aim of this study was to investigate
      the effect of treadmill exercise (20min/day during 2 weeks) on H3K9, H4K5 and
      H4K12 acetylation levels in hippocampi of young adult and aged rats. Male Wistar
      rats aged 3 or 20-21 months were assigned to sedentary and exercise groups.
      Single-trial step-down inhibitory avoidance conditioning was employed as an
      aversive memory paradigm. Hippocampal H3K9, H4K5 and H4K12 acetylation was
      determined by Western blotting. The daily moderate exercise protocol improved the
      aversive memory performance and increased hipocampal H4K12 acetylation levels in
      both tested ages. Exercise was also able to increase H3K9 acetylation levels in
      aged rats. An age-related decline in memory performance was observed, without any
      effect of the aging process on histone acetylation state. Our data suggest that
      treadmill exercise can impact hippocampal the histone acetylation profile in an
      age- and lysine-dependent manner. In addition, higher hippocampal H4K12
      acetylation levels at both ages may be related to improvement of aversive memory
      performance.

PMID- 27717827
TI  - Low d-serine levels in schizophrenia: A systematic review and meta-analysis.
AB  - An increasing amount of evidence indicates that d-serine, a potent and selective
      endogenous coagonist of the N-methyl-d-aspartate receptor (NMDAR), is efficacious
      in the treatment of schizophrenia. Although the therapeutic efficacy of d-serine
      supplementation is based on the d-serine deficit and NMDAR hypofunction
      hypothesis, it has not been confirmed whether d-serine levels are decreased in
      patients with schizophrenia compared to healthy controls. We searched the
      following electronic databases: Embase, Ovid Medline, and the Cochrane Library. A
      total of 20 studies were included in our meta-analysis. Serum d-serine levels
      were significantly decreased in patients with schizophrenia (standardized mean
      difference (SMD)=-1.008, 95% CI=-1.827 to -0.190). In the meta-regression
      analysis, male gender was positively correlated with serum d-serine levels
      (coefficient=0.190, 95% CI=0.070 to 0.311). d-Serine therapy combined with
      antipsychotics significantly improved negative (SMD=-0.319, 95% CI=-0.576 to 
      0.061) and positive (SMD=-0.211, 95% CI=-0.413 to -0.009) symptoms in patients
      with schizophrenia. Our results suggest that decreased d-serine availability may
      justify combining d-serine therapy with antipsychotics in patients with
      schizophrenia. However, clinical methodological heterogeneity across studies
      should be considered a major limitation of this analysis.

PMID- 27717828
TI  - Spinal CXCL5 contributes to nerve injury-induced neuropathic pain via modulating
      GSK-3beta phosphorylation and activity in rats.
AB  - BACKGROUND: Neuroinflammation is identified to be crucial in the development of
      neuropathic pain, whereas definite molecular mechanisms remain obscure. Recently,
      chemokine CXCL5 is manifested to participate in the inflammatory process of
      central nervous system, however, little is known about the potential effect of
      spinal CXCL5 on pathogenesis of pain. This study investigated whether and how
      CXCL5 and its receptor CXCR2 regulated neuropathic pain in a rat model of chronic
      constriction injury (CCI) of the sciatic nerves. METHODS: Recombinant CXCL5, a
      neutralizing antibody against CXCL5, selective CXCR2 antagonist SB225002 and GSK
      3beta inhibitor TDZD-8 were injected intrathecally. PWT and PWL were documented
      to assess mechanical allodynia and thermal hyperalgesia. Simultaneously, levels
      of CXCL5 and CXCR2 in spinal dorsal horn were measured by RT-qPCR after
      nociceptive testing. Western blot was utilized to evaluate spinal GSK-3beta
      expression and phosphorylation. RESULTS: We found that CCI engendered rapid and
      long-lasting mechanical allodynia and thermal hyperalgesia, which was accompanied
      by dramatical rise of spinal CXCL5 and CXCR2 expression. CCI also caused an
      increase of pGSK-3beta (Tyr216) and a decrease of pGSK-3beta (Ser9) without
      affecting total protein level of GSK-3beta. Moreover, spinal blockage of
      CXCL5/CXCR2 pathway attenuated neuropathic pain and inhibited the enhancement of
      GSK-3beta activity. Also, intrathecal delivery of exogenous CXCL5 dose
      dependently induced nociceptive hypersensitivity in naive rats, which was
      prevented by the supplemental addition of TDZD-8. CONCLUSION: These present
      findings indicate that up-regulation of spinal CXCL5 and CXCR2 is involved in
      neuropathic pain after nerve injury, through regulating GSK-3beta activity in
      rats.

PMID- 27717829
TI  - Effects of (-)-sesamin on chronic stress-induced memory deficits in mice.
AB  - This study investigated the effects of (-)-sesamin on memory deficits induced by
      chronic electric footshock (EF)-induced stress in mice. Mice were treated with (
      )-sesamin (25 and 50mg/kg, p.o., daily for 21day) prior to chronic EF stress
      (0.6mA, 1s every 5s for 3min, daily for 21day). Transfer retention latencies in
      the elevated plus maze test and N-methyl-d-aspartate (NMDA) receptor (type 1)
      phosphorylation in the hippocampus increased with chronic EF stress, and they
      were reduced by treatment with (-)-sesamin at both doses. Phosphorylation of
      extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-responsive element
      binding protein (CREB), which were reduced by chronic EF stress, were increased
      by treatment with (-)-sesamin. Retention latencies in the passive avoidance test
      and dopamine levels in the substantia nigra-striatum were also reduced by chronic
      EF stress, and similarly recovered with (-)-sesamin treatment. These results
      suggest that (-)-sesamin ameliorates the effects of chronic EF stress-induced
      spatial and habit learning memory deficits by modulating both NMDA receptor and
      dopaminergic neuronal systems.

PMID- 27717830
TI  - Duration of untreated illness as a key to early intervention in schizophrenia: A
      review.
AB  - The first psychotic episode is classically viewed as a critical period which
      management is important in determining the long-term outcome of the schizophrenia
      (SCZ). For this reason, the duration of untreated illness (DUI), defined as the
      interval between the onset of the psychiatric disorder and the administration of
      the first pharmacological treatment, is a clinical variable that has been
      increasingly investigated due to its potentially modifiable nature and its value
      as a predictor of outcome. DUI is poorly applicable and highly unreliable in
      psychosis. The present critical review examines the impact of DUI and its more
      operative definition of "duration of untreated psychosis" (DUP) in the course and
      outcome of SCZ, focusing on its epidemiologic, clinical, prognostic factors.
      Length of DUP has been identified as positively related to a worst treatment
      response, symptom control and overall functional outcome in SCZ. Negative
      symptoms appear to be prominently related to longer DUP. Neuroimaging correlates
      of DUP have not been clearly outlined: few of the studies considering first
      episode patients and DUP showed structural abnormalities. A low proportion of
      significant associations were found mostly in cerebellum and occipital lobe of
      patients with longer DUP. Also, evidence of an inverse correlation between
      cognitive alterations and DUP is not conclusive. DUI and DUP are multidimensional
      constructs that imply both intrinsic, illness related (e.g. subtle symptoms at
      onset) and extrinsic factors (e.g. access to mental health services), so that
      from its study sprouted in the last decades First-Episode Units, aimed at
      providing secondary prevention in SCZ such as providing a timely diagnosis and
      treatment to patients experiencing their first psychotic episode. Early
      intervention seems to ensure a shortened DUP, especially for people presenting
      with brief limited intermittent psychotic symptoms, and, ultimately, ensure a
      more favorable prognosis for patients affected by SCZ.

PMID- 27717831
TI  - Religious and spiritual importance moderate relation between default mode network
      connectivity and familial risk for depression.
AB  - Individuals at high risk for depression have increased default mode network (DMN)
      connectivity, as well as reduced inverse connectivity between the DMN and the
      central executive network (CEN) [8]. Other studies have indicated that the belief
      in the importance of religion/spirituality (R/S) is protective against depression
      in high risk individuals [5]. Given these findings, we hypothesized that R/S
      importance would moderate DMN connectivity, potentially reducing DMN connectivity
      or increasing DMN-CEN inverse connectivity in individuals at high risk for
      depression. Using resting-state functional connectivity MRI (rs-fcMRI) in a
      sample of 104 individuals (aged 11-60) at high and low risk for familial
      depression, we previously reported increased DMN connectivity and reduced DMN-CEN
      inverse connectivity in high risk individuals. Here, we found that this effect
      was moderated by self-report measures of R/S importance. Greater R/S importance
      in the high risk group was associated with decreased DMN connectivity. These
      results may represent a protective neural adaptation in the DMN of individuals at
      high risk for depression, and may have implications for other meditation-based
      therapies for depression.

PMID- 27717832
TI  - Hormonal modulation of novelty processing in women: Enhanced under working memory
      load with high dehydroepiandrosterone-sulfate-to-dehydroepiandrosterone ratios.
AB  - Several studies have suggested that dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone-sulfate (DHEAS) may enhance working memory and attention,
      yet current evidence is still inconclusive. The balance between both forms of the
      hormone might be crucial regarding the effects that DHEA and DHEAS exert on the
      central nervous system. To test the hypothesis that higher DHEAS-to-DHEA ratios
      might enhance working memory and/or involuntary attention, we studied the DHEAS
      to-DHEA ratio in relation to involuntary attention and working memory processing
      by recording the electroencephalogram of 22 young women while performing a
      working memory load task and a task without working memory load in an audio
      visual oddball paradigm. DHEA and DHEAS were measured in saliva before each task.
      We found that a higher DHEAS-to-DHEA ratio was related to enhanced auditory
      novelty-P3 amplitudes during performance of the working memory task, indicating
      an increased processing of the distracter, while on the other hand there was no
      difference in the processing of the visual target. These results suggest that the
      balance between DHEAS and DHEA levels modulates involuntary attention during the
      performance of a task with cognitive load without interfering with the processing
      of the task-relevant visual stimulus.

PMID- 27717833
TI  - Genetic analysis of the CHCHD2 gene in Chinese patients with familial essential
      tremor.
AB  - Recently, Funayama et al. identified CHCHD2 as a novel causative gene of
      Parkinson disease (PD). However, the relationship between CHCHD2 and essential
      tremor (ET) patients was still unknown. Genetic analysis of CHCHD2 gene was
      conducted in 60 probands of ET families with autosomal dominant inheritance and
      90 healthy controls in Chinese population. No pathogenic CHCHD2 mutation was
      found in ET patients. However, we identified one rare variant, c.5C>T, a reported
      risk variant for sporadic PD in Japanese populations, and examined the frequency
      of three common variants. Our results suggested that CHCHD2 mutations may be rare
      in Chinese familial ET patients.

PMID- 27717835
TI  - A resting-state fMRI study on early-stage drug-naive Parkinson's disease patients
      with drooling.
AB  - OBJECTIVE: Drooling is a common symptom in Parkinson's disease (PD). This study
      used resting-state functional MRI (fMRI) to evaluate the brain connectivity of
      cortico-striatal circuits in PD patients with drooling. METHOD: We enrolled 30
      early-stage drug-naive PD patients and 30 matched normal controls. Among the PD
      patients, 15 patients were classified as "droolers" with the presence of drooling
      and 15 patients as "non-droolers" with the absence of drooling. All participants
      underwent resting-state fMRI scans on a 3-T MR system, focusing on the functional
      connectivity of striatum subregions. RESULTS: Compared with PD patients without
      drooling, PD patients with drooling showed the significantly reduced functional
      connectivity of putamen within bilateral sensorimotor cortices, superior and
      inferior parietal lobules and areas in the right occipital and temporal lobes. No
      increased functional connectivity was found between the two PD subgroups. In
      addition, compared with healthy controls, both PD subgroups showed the functional
      connectivity alterations in cortico-striatal loops. The decreased functional
      connectivity was prominent in the most affected posterior putamen, and the
      increased functional connectivity was evident only in the relatively unaffected
      anterior striatum and caudate. CONCLUSION: By studying a cohort of early-stage
      drug-naive PD patients, we eliminated the potential confounding effects of
      antiparkinson medication on the functional integration of neural networks. We
      demonstrated decreased connectivity within cortico-striatal networks in PD
      patients with drooling. These findings might be helpful for promoting the further
      understanding of neural system effects underlying drooling in PD. Our result is
      preliminary and further investigation is needed.

PMID- 27717834
TI  - Does medial temporal lobe thickness mediate the association between risk factor
      burden and memory performance in middle-aged or older adults with metabolic
      syndrome?
AB  - Metabolic syndrome (MetS) is a cluster of cardiovascular and metabolic
      abnormalities that together may increase the risk of developing cognitive decline
      and dementia; however, the neural substrate is incompletely understood. We
      investigated cortical thickness in the medial temporal lobe (MTL), hippocampal
      volume, as well as relationships among metabolic risk factor burden, structure
      and memory performance. Path-analytic models were tested to explore the relations
      between MetS risk factor, structure and memory performance. Participants were 65
      non-demented, middle-aged and older adults, 34 with and 31 without metabolic
      syndrome. We analyzed archival T1-weighted magnetic resonance imaging (MRI)
      acquired at 3T and Total Recall and Delayed Recall scores from the Brief
      Visuospatial Memory Test Revised (BVMT-R). Middle-aged adults with MetS showed
      less MTL thickness, particularly in entorhinal cortex; while older adults showed
      a trend for left hippocampal volume loss. Lower MTL thickness, particularly in
      entorhinal cortex, was associated with greater metabolic risk factor burden in
      middle-aged adults. In older adults, hippocampal volume was associated with Total
      Recall and Delayed Recall, while in middle-age entorhinal cortical thickness
      mediated the association between metabolic disease burden and episodic memory
      function. The differential findings in middle-aged and older adults with MetS
      contribute to an understanding of the relationships between metabolic syndrome,
      structural changes in the brain and increased risk for cognitive decline.

PMID- 27717836
TI  - Managing hypertriglyceridemia in children with systemic lupus erythematosus: Two
      sides of the same coin.
AB  - Hypertriglyceridemia is common in children with systemic lupus erythematosus
      (SLE). A retrospective analysis of the baseline clinical-pathological
      presentation and treatment outcome (status of lipid profiles) was performed in
      two children with SLE, who presented with extreme hypertriglyceridemia over a
      follow-up period of four weeks. The children were treated with prednisolone,
      mycophenolate mofetil (MMF), hydroxychloroquine and hypolipidemic agents,
      depending on their disease status. On serial follow-up, the first child showed a
      significantly raised serum triglyceride level after receiving one week of oral
      prednisolone therapy. Anti-lipoprotein-lipase (LPL) autoantibody was absent.
      Lipid profile levels of this child gradually improved after replacing oral
      prednisolone with another immunosuppressant, namely MMF. The second child
      presented with extreme hypertriglyceridemia with positive anti-LPL autoantibody.
      She responded to plasmapheresis followed by increasing the dose of
      immunosuppressant. So, extreme hypertriglyceridemia in children with SLE may be
      steroid induced or due to presence of anti-LPL auto antibody. Management should
      be individualized depending on the etiology.

PMID- 27717838
TI  - Replantation or revascularization for the treatment of hand degloving injuries.
AB  - PURPOSE: The purpose of this study was to explore effective strategies of
      replantation or revascularization for the treatment of hand degloving injuries.
      METHODS: Ten patients who had received replantation or revascularization surgery
      for hand degloving injury between 2002 and 2014 were included for this study. The
      average age at the time of surgery was 34.5 years (range 18-49 years). There were
      nine left and one right hand replantations. The cause of injury was an industrial
      machine press in all of them. The skin was avulsed from the palm to the distal
      phalangeal level in five patients, to the middle phalangeal level in four
      patients, and avulsed from the wrist crease level completely in one patient. All
      the degloved flaps were revascularized. RESULTS: Both the degloved flap and
      phalanges survived completely in one patient, and partial survival of the flap
      occurred in the remaining patients. The patients were followed up from 15 months
      to 78 months (average, 38.1 months). Sensory recovery of the finger pulp ranged
      from S2 to S3+. Michigan Hand outcome Questionnaire (MHQ) score ranged from 29 to
      96 with an average of 69.5. CONCLUSIONS: Midlateral incision to reduce the
      secondary damage to the capillaries, repair of more vessels for circulation,
      application of full-thickness skin grafts to enlarge the survival area, and use
      of anticoagulation protocols during and postsurgery may be beneficial to improve
      the replantation survival of the degloved skin.

PMID- 27717839
TI  - Is the snail shell repair process really influenced by eggshell membrane as a
      template of foreign scaffold?
AB  - Biominerals are inorganic-organic hybrid composites formed via self-assembled
      bottom up processes under mild conditions. Biominerals show interesting physical
      properties, controlled hierarchical structures and robust remodeling or repair
      mechanisms. Biological processes associated with biominerals remain to be
      developed into practical engineering processes. Therefore, the formation of
      biominerals is inspiring for the design of materials, especially those fabricated
      at ambient temperatures. The study described herein involves the influence of
      chicken outer eggshell membrane on the type of calcium carbonate (CaCO3)
      polymorph deposited on the shell of the land snail Helix aspersa during the
      repair process after an injury. A piece of snail shell was removed by perforating
      a hole from the largest body whorl. The operated area was left either uncovered
      or covered with either a thermoplastic flexible polyolefin-based film Parafilm(r)
      or a piece of chicken eggshell membrane. The repaired shells of control and
      experimental animals were analyzed using SEM, EDS, Raman and FTIR spectroscopies.
      We found that in the presence of eggshell membrane, the polymorph deposited on
      the substratum during the first hours resembles calcite, the polymorph present in
      eggshell normal formation, but at 24 and 48h, when snail mantle cells produced
      their normal organic matrix (mainly beta-chitin plus proteins and proteoglycans),
      the polymorph deposited is aragonite, the characteristic polymorph of Helix
      shell. Therefore, the eggshell membrane influences the type of polymorph, but
      only in the initial stages of biomineral deposition, before an organic matrix
      layer is deposited by the snail.

PMID- 27717840
TI  - Analysis of nasal potential in murine cystic fibrosis models.
AB  - The nasal epithelium of the mouse closely mimics the bioelectrical phenotype of
      the human airways. Ion transport across the nasal epithelium induces a nasal
      transepithelial potential difference. Its measurement by a relatively non
      invasive method adapted from humans allows in vivo longitudinal measurements of
      CFTR-dependent ionic transport in the murine nasal mucosa. This test offers a
      useful tool to assess CFTR function in preclinical studies for novel therapeutics
      modulating CFTR activity. Here we extensively review work done to assess
      transepithelial transport in the murine respiratory epithelium in the basal state
      and after administration of CFTR modulators. Factors of variability and
      discriminative threshold between the CF and the WT mice for different readouts
      are discussed.

PMID- 27717837
TI  - An integrative view of cisplatin-induced renal and cardiac toxicities: Molecular
      mechanisms, current treatment challenges and potential protective measures.
AB  - Cisplatin is currently one of the most widely-used chemotherapeutic agents
      against various malignancies. Its clinical application is limited, however, by
      inherent renal and cardiac toxicities and other side effects, of which the
      underlying mechanisms are only partly understood. Experimental studies show
      cisplatin generates reactive oxygen species, which impair the cell's antioxidant
      defense system, causing oxidative stress and potentiating injury, thereby
      culminating in kidney and heart failure. Understanding the molecular mechanisms
      of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent
      or treat this problem better and may also provide a model for investigating drug
      induced organ toxicity in general. This review discusses some of the major
      molecular mechanisms of cisplatin-induced renal and cardiac toxicities including
      disruption of ionic homeostasis and energy status of the cell leading to cell
      injury and cell death. We highlight clinical manifestations of both toxicities as
      well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue
      inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic
      peptide (NT-proBNP). We also present some current treatment challenges and
      propose potential protective strategies including combination therapy with novel
      pharmacological compounds that might mitigate or prevent these toxicities, which
      include the use of hydrogen sulfide.

PMID- 27717841
TI  - A high-throughput screen for mitochondrial function reveals known and novel
      mitochondrial toxicants in a library of environmental agents.
AB  - Mitochondrial toxicity is emerging as a major mechanism underlying serious human
      health consequences. This work performs a high-throughput screen (HTS) of 176
      environmental chemicals for mitochondrial toxicity utilizing a previously
      reported biosensor platform. This established HTS confirmed known mitochondrial
      toxins and identified novel mitotochondrial uncouplers such as 2, 2'
      Methylenebis(4-chlorophenol) and pentachlorophenol. It also identified a
      mitochondrial 'structure activity relationship' (SAR) in the sense that multiple
      environmental chlorophenols are mitochondrial inhibitors and uncouplers. This
      study demonstrates proof-of-concept that a mitochondrial HTS assay detects known
      and novel environmental mitotoxicants, and could be used to quickly evaluate
      human health risks from mitotoxicants in the environment.

PMID- 27717842
TI  - Education, Employment, Income, and Marital Status Among Adults Diagnosed With
      Inflammatory Bowel Diseases During Childhood or Adolescence.
AB  - BACKGROUND & AIMS: We aimed to assess levels of education attained, employment,
      and marital status of adults diagnosed with inflammatory bowel diseases (IBD)
      during childhood or adolescence, compared with healthy individuals in Canada.
      METHODS: We performed a cross-sectional study of adults diagnosed with IBD in
      childhood or adolescence at Children's Hospital in Winnipeg, Manitoba from
      January 1978 through December 2007. Participants (n = 112) answered a semi
      structured questionnaire on educational achievements, employment, and marital
      status. Patients were matched for age and sex with random healthy individuals
      from the 2012 Canadian Community Health Survey (controls, 5 per patient).
      Conditional binary logistic regression and random-effects ordinal logistic
      regression models were used for analysis. RESULTS: Patients were followed for a
      mean duration of 14.3 years (range, 3.1-34.5 years). Persons with IBD were more
      likely to earn more money per annum and attain a post-secondary school degree or
      receive a diploma than controls (odds ratio, 1.72; 95% confidence interval, 1.13
      2.60; P < .01 and odds ratio, 2.73; 95% confidence interval, 1.48-5.04; P < .01,
      respectively). There was no significant difference between patients and controls
      in employment or marital status. CONCLUSIONS: Adults diagnosed with IBD during
      childhood seem to achieve higher education levels than individuals without IBD.
      This observation should provide reassurance to children with IBD and their
      parents. ClinicalTrials.gov number: NCT02152241.

PMID- 27717843
TI  - Homology modeling of Homo sapiens lipoic acid synthase: Substrate docking and
      insights on its binding mode.
AB  - Lipoic acid synthase (LIAS) is an iron-sulfur cluster mitochondrial enzyme which
      catalyzes the final step in the de novo pathway for the biosynthesis of lipoic
      acid, a potent antioxidant. Recently there has been significant interest in its
      role in metabolic diseases and its deficiency in LIAS expression has been linked
      to conditions such as diabetes, atherosclerosis and neonatal-onset epilepsy,
      suggesting a strong inverse correlation between LIAS reduction and disease
      status. In this study we use a bioinformatics approach to predict its structure,
      which would be helpful to understanding its role. A homology model for LIAS
      protein was generated using X-ray crystallographic structure of
      Thermosynechococcus elongatus BP-1 (PDB ID: 4U0P). The predicted structure has
      93% of the residues in the most favour region of Ramachandran plot. The active
      site of LIAS protein was mapped and docked with S-Adenosyl Methionine (SAM) using
      GOLD software. The LIAS-SAM complex was further refined using molecular dynamics
      simulation within the subsite 1 and subsite 3 of the active site. To the best of
      our knowledge, this is the first study to report a reliable homology model of
      LIAS protein. This study will facilitate a better understanding mode of action of
      the enzyme-substrate complex for future studies in designing drugs that can
      target LIAS protein.

PMID- 27717844
TI  - Equilibria of oligomeric proteins under high pressure - A theoretical
      description.
AB  - High pressure methods have become a useful tool for studying protein structure
      and stability. Using them, various physico-chemical processes including protein
      unfolding, aggregation, oligomer dissociation or enzyme-activity decrease were
      studied on many different proteins. Oligomeric protein dissociation is a process
      that can perfectly utilize the potential of high-pressure techniques, as the high
      pressure shifts the equilibria to higher concentrations making them better
      observable by spectroscopic methods. This can be especially useful when the
      oligomeric form is highly stable at atmospheric pressure. These applications may
      be, however, hindered by less intensive experimental response as well as
      interference of the oligomerization equilibria with unfolding or aggregation of
      the subunits, but also by more complex theoretical description. In this study we
      develop mathematical models describing different kinds of oligomerization
      equilibria, both closed (equilibrium of monomer and the highest possible oligomer
      without any intermediates) and consecutive. Closed homooligomer equilibria are
      discussed for any oligomerization degree, while the more complex heterooligomer
      equilibria and the consecutive equilibria in both homo- and heterooligomers are
      taken into account only for dimers and trimers. In all the cases, fractions of
      all the relevant forms are evaluated as functions of pressure and concentration.
      Significant points (inflection points and extremes) of the resulting transition
      curves, that can be determined experimentally, are evaluated as functions of
      pressure and/or concentration. These functions can be further used in order to
      evaluate the thermodynamic parameters of the system, i.e. atmospheric-pressure
      equilibrium constants and volume changes of the individual steps of the oligomer
      dissociation processes.

PMID- 27717846
TI  - microRNA-539 suppresses tumor growth and tumorigenesis and overcomes arsenic
      trioxide resistance in hepatocellular carcinoma.
AB  - AIMS: Dysregulation of microRNAs (miRNAs) plays a critical role in tumor growth
      and progression. In this study, we sought to explore the expression and
      biological roles of miR-539 in hepatocellular carcinoma (HCC). MAIN METHODS: The
      expression of miR-539 in human HCC tissues and cell lines was examined. The
      effects of miR-539 overexpression on cell growth, tumorigenicity, arsenic
      trioxide resistance of HCC cells were determined. The signaling pathways involved
      in the action of miR-539 in HCC were also investigated. KEY FINDINGS: miR-539 was
      downregulated in HCC tissues and cells, relative to corresponding controls.
      Overexpression of miR-539 inhibited HCC cell viability and colony formation in
      vitro and impaired tumorigenesis of HCC cells in vivo. Transfection with miR-539
      mimic significantly induced apoptosis in HepG2 cells, which was coupled with
      reduced expression of anti-apoptotic proteins Bcl-2 and Bcl-xL and decreased
      phosphorylation of Stat3. Overexpression of a constitutively active form of Stat3
      partially blocked miR-539-mediated apoptosis. Enforced expression of miR-539
      resensitized arsenic trioxide-resistant HCC cells to arsenic trioxide.
      Intratumoral delivery of miR-539 mimic significantly retarded the growth of
      xenograft tumors from arsenic trioxide-resistant HCC cells by about 35%, compared
      to delivery of control miRNA (P<0.05). In combination with arsenic trioxide, miR
      539 mimic yielded about 80% decrease in tumor burden. SIGNIFICANCE: miR-539
      functions as a tumor suppressor in HCC and reexpression of this miRNA offers a
      potential therapeutic strategy for this disease.

PMID- 27717845
TI  - Janus kinase 2 activation participates in prostaglandin E2-induced hyperalgesia.
AB  - Prostaglandin E2 (PGE2) is one of the major signaling molecules involved in
      hyperalgesia, acting directly on nociceptors and resulting in the activation of
      PKA and PKC. Once active, these kinases phosphorylate many cellular proteins,
      resulting in changes on nociceptors sensorial transduction properties. The Janus
      Kinases (JAKs) are a family of intracellular signaling molecules generally
      associated with cytokine signaling, and their activity can be increased in
      nociceptors after peripheral inflammation. However, there are no evidences of
      JAKs direct involvement in PGE2 mediated sensitization of nociceptors. Therefore,
      the aim of the present study was to explore a possible role for JAKs in PGE2
      mediated sensitization. In cultured dorsal root ganglion (DRG) neurons, we
      observed that the administration of PGE2 increases capsaicin induced calcium
      transients, and a pre-incubation of DRG cells with the JAK inhibitor AG490 blocks
      this PGE2 in vitro effect. Intrathecal administration of AG490 to ten-weeks-old
      male Wistar rats reduces the hyperalgesia induced by the intraplantar
      administration of PGE2 or carrageenan in the right hind paw. We also observed
      that carrageenan administration in the right hind paw induced an increase in
      membrane associated PKCepsilon in the ipsilateral L5 DRG, and this increase was
      blocked by intrathecal AG490 administration. In conclusion the present study
      indicates that the JAKs expressed in the DRG and spinal cord may have a role in
      the sensitization of nociceptors by a peripheral inflammatory event. Moreover,
      the inhibition of JAKs may be a possible novel pharmacological target for the
      control of the inflammatory hyperalgesia.

PMID- 27717847
TI  - An updated meta-analysis of transforming growth factor-beta1 gene: Three well
      characterized polymorphisms with asthma.
AB  - The association between TGF-beta1 polymorphisms and asthma risk has been widely
      reported, but results were controversial. We performed this meta-analysis based
      on the Preferred Reporting Items for Systematic Reviews and meta-analyses
      statement (PRISMA). Electronic database of Pub Med, Web of Science, CBM, and CNKI
      were searched for eligible articles published up to September, 2013. The effect
      summary odds ratio (OR) and 95% confidence intervals were obtained. Finally, a
      total of 20 articles were identified, 17 studies with 3694 cases and 5613
      controls for C-509T polymorphism, 7 studies with 1109 cases and 1098 controls for
      T869C polymorphism and 5 studies with 849 cases and 829 controls for G915C
      polymorphism. For C-509T, significant associations with asthma were found in
      Asians (TT+TC vs. CC: P=0.004, OR=1.43, 95%CI=1.12-1.81, Pheterogeneity=0.001)
      and in Caucasians (P=0.05, OR=1.16, 95%CI=1.00-1.34, Pheterogeneity=0.36). With
      respect to T869C, a small significant association was observed in overall
      analysis of allele contrasts(C vs. T: OR=1.14, 95%CI: 1.01-1.29, P=0.03) and
      homozygote comparison (CC vs. TT: OR=1.29, 95%CI: 1.00-1.65, P=0.05), but no
      significant risks were found among Caucasian population and Asian population. For
      G915C polymorphism, no significant association with asthma risk was demonstrated
      in overall analysis and subgroup analyses according to ethnicity for all genetic
      models. This meta-analysis suggested that TGF-beta1 C-509T and T869C
      polymorphisms may be risk factors for asthma.

PMID- 27717849
TI  - Am I or am I not proarrhythmic? Comparison of various classifications of drug TdP
      propensity.
AB  - This review aims to present and compare various Torsade de pointes propensity
      classification schemes of drugs that are publicly available from many scientific
      sources. We have also tracked and listed the compounds that were differently
      categorized. Additionally, we would like to draw attention to the need for
      establishing a general, standardized classification of a drug's proarrhythmic
      propensity. This is especially important in the current drug development process
      because of the changing paradigm of drug cardiac safety assessment.

PMID- 27717848
TI  - Colon cancer-derived myofibroblasts increase endothelial cell migration by
      glucocorticoid-sensitive secretion of a pro-migratory factor.
AB  - Angiogenesis is important in cancer progression and can be influenced by tumor
      associated myofibroblasts. We addressed the hypothesis that glucocorticoids
      indirectly affect angiogenesis by altering the release of pro-angiogenic factors
      from colon cancer-derived myofibroblasts. Our study shows that glucocorticoids
      reduced prostanoids, urokinase-type plasminogen activator (uPA) and angiopoietin
      like protein-2 (ANGPTL2) levels, but increased angiogenin (ANG) in supernatant
      from human CT5.3hTERT colon cancer-derived myofibroblasts. Conditioned medium
      from solvent- (CMS) and dexamethasone (Dex)-treated (CMD) myofibroblasts
      increased human umbilical vein endothelial cell (HUVEC) proliferation, but did
      not affect expression of pro-angiogenic factors or tube-like structure formation
      (by HUVECs or human aortic ECs). In a HUVEC scratch assay CMS-induced
      acceleration of wound healing was blunted by CMD treatment. Moreover, CMS-induced
      neovessel growth in mouse aortic rings ex vivo was also blunted using CMD. The
      latter effect could be ascribed to both Dex-driven reduction of secreted factors
      and potential residual Dex present in CMD (indicated using a dexamethasone-spiked
      CMS control). A similar control in the scratch assay, however, revealed that
      altered levels of factors in the CMD, and not potential residual Dex, were
      responsible for decreased wound closure. In conclusion, our results suggest that
      glucocorticoids indirectly alter endothelial cell function during tumor
      development in vivo.

PMID- 27717851
TI  - Tuberculosis drug discovery needs public-private consortia.

PMID- 27717852
TI  - Personality and problem-solving in common mynas (Acridotheres tristis).
AB  - Animals show consistent individual differences in behaviour across time and/or
      contexts. Recently, it has been suggested that proactive personality types might
      also exhibit fast cognitive styles. The speed with which individuals sample
      environmental cues is one way in which correlations between personality and
      cognition might arise. Here, we measured a collection of behavioural traits
      (competitiveness, neophobia, neophilia, task-directed motivation and exploration)
      in common mynas (Acridotheres tristis) and measured their relationship with
      problem solving. We predicted that fast solving mynas would interact with (i.e.
      sample) the problem solving task at higher rates, but also be more competitive,
      less neophobic, more neophilic, and more exploratory. Mynas that were faster to
      solve a novel foraging problem were no more competitive around food and no more
      inclined to take risks. Unexpectedly, these fast-solving mynas had higher rates
      of interactions with the task, but also displayed lower levels of exploration. It
      is possible that a negative relation between problem solving and spatial
      exploration arose as a consequence of how inter-individual variation in
      exploration was quantified. We discuss the need for greater consensus on how to
      measure exploratory behaviour before we can advance our understanding of
      relationships between cognition and personality more effectively.

PMID- 27717850
TI  - Learning from the past for TB drug discovery in the future.
AB  - Tuberculosis drug discovery has shifted in recent years from a primarily target
      based approach to one that uses phenotypic high-throughput screens. As examples
      of this, through our EU-funded FP7 collaborations, New Medicines for Tuberculosis
      was target-based and our more-recent More Medicines for Tuberculosis project
      predominantly used phenotypic screening. From these projects we have examples of
      success (DprE1) and failure (PimA) going from drug to target and from target to
      drug, respectively. It is clear that we still have much to learn about the drug
      targets and the complex effects of the drugs on Mycobacterium tuberculosis. We
      propose a more integrated approach that learns from earlier drug discovery
      efforts that could help to move drug discovery forward.

PMID- 27717853
TI  - Determination of collagen type IV by Surface Plasmon Resonance Imaging using a
      specific biosensor.
AB  - Serum collagen type IV (COLIV) is a promising tumor marker. High COLIV
      concentrations have been found in the serum of patients with colorectal, gastric,
      lung, liver and breast cancers. The aim of this work was to develop a biosensor
      for use with the Surface Plasmon Resonance Imaging (SPRI) technique for COLIV
      determination. The biosensor consists of glass covered with gold and immobilized
      monoclonal mouse anti-human collagen type IV antibody via cysteamine linker. The
      biosensor works selectively within a dynamic response range between 10 and 300 ng
      mL-1, with LOD 2.4 ng mL-1 and LOQ 8 ng mL-1. The precision of determination is
      4.7% at a 150 ng mL-1 COLIV spike and 8.0% at a 20 ng mL-1 spike, with recoveries
      of 101% and 106% respectively. A 100-fold excess of collagen I, albumin, laminin
      and fibronectin is tolerated. The average COLIV blood plasma concentration of
      healthy donors determined by the developed method was 69 +/- 10 ng mL-1, while
      the median of six results available in the literature was approximately 80 ng mL
      1. The average COLIV blood plasma concentration of breast cancer patients was 360
      +/- 68 ng mL-1, showing the high potential of COLIV as a marker of this type of
      cancer.

PMID- 27717854
TI  - Optimization of the formation of embedded multicellular spheroids of MCF-7 cells:
      How to reliably produce a biomimetic 3D model.
AB  - To obtain a multicellular MCF-7 spheroid model to mimic the three-dimensional
      (3D) of tumors, the microwell liquid overlay (A) and hanging-drop/agar (B)
      methods were first compared for their technical parameters. Then a method for
      embedding spheroids within collagen was optimized. For method A, centrifugation
      assisted cells form irregular aggregates but not spheroids. For method B, an
      extended sedimentation period of over 24 h for cell suspensions and increased
      viscosity of the culture medium using methylcellulose were necessary to harvest a
      dense and regular cell spheroid. When the number was less than 5000 cells/drop,
      embedded spheroids showed no tight cores and higher viability than the
      unembedded. However, above 5000 cells/drop, cellular viability of embedded
      spheroids was not significantly different from unembedded spheroids and cells
      invading through the collagen were in a sun-burst pattern with tight cores.
      Propidium Iodide staining indicated that spheroids had necrotic cores. The
      doxorubicin cytotoxicity demonstrated that spheroids were less susceptible to DOX
      than their monolayer cells. A reliable and reproducible method for embedding
      spheroids using the hanging-drop/agarose method within collagen is described
      herein. The cell culture model can be used to guide experimental manipulation of
      3D cell cultures and to evaluate anticancer drug efficacy.

PMID- 27717855
TI  - Isothermal titration calorimetry for drug design: Precision of the enthalpy and
      binding constant measurements and comparison of the instruments.
AB  - Isothermal titration calorimetry (ITC) is one of the most robust label- and
      immobilization-free techniques used to measure protein - small molecule
      interactions in drug design for the simultaneous determination of the binding
      affinity (DeltaG) and the enthalpy (DeltaH), both of which are important
      parameters for structure-thermodynamics correlations. It is important to evaluate
      the precision of the method and of various ITC instrument models by performing a
      single well-characterized reaction. The binding between carbonic anhydrase II and
      acetazolamide was measured by four ITC instruments - PEAQ-ITC, iTC200, VP-ITC,
      and MCS-ITC and the standard deviation of DeltaG and DeltaH was determined.
      Furthermore, the limit of an approach to reduce the protein concentration was
      studied for a high-affinity reaction (Kd = 0.3 nM), too tight to be measured by
      direct (non-displacement) ITC. Chemical validation of the enthalpy measurements
      is discussed.

PMID- 27717857
TI  - Localized surface plasmon resonance based gold nanobiosensor: Determination of
      thyroid stimulating hormone.
AB  - An immunoassay method based on the peak shift of the localized surface plasmon
      resonance (LSPR) absorption maxima has been developed for the determination of
      the thyroid stimulating hormone (TSH) in human blood serum. The anti-TSH antibody
      was adsorbed on the synthesized gold nanoparticles by electrostatic forces. The
      efficiency of the nanobiosensor was improved by optimizing the factors affecting
      the probe construction such as the pH and the antibody to gold nanoparticles
      ratio. Dynamic light scattering was applied for the characterization of the
      constructed probe. The amount of peak shift of the LSPR absorption maxima was
      selected as the basis for determination of TSH antigen. The linear dynamic range
      of 0.4-12.5 mIU L-1 and the calibration sensitivity of 1.71 L mIU-1 were
      obtained. The human control serum sample was analyzed for TSH by constructed
      nanobiosensor and the acceptable results were obtained.

PMID- 27717856
TI  - Triglyceride depletion of brown adipose tissue enables analysis of mitochondrial
      respiratory function in permeabilized biopsies.
AB  - The research on mitochondrial functions in adipocytes has increasingly evidenced
      that mitochondria plays an important role in the onset and/or progression of
      obesity and related pathologies. Mitochondrial function in brown adipose tissue
      (BAT) has been classically assessed by measuring either the levels/activity of
      mitochondrial enzymes, or the respiration in isolated mitochondria. Isolation of
      mitochondria is not advantageous because it demands significant time and amount
      of tissue and, as tissue homogenates, disrupts biochemical and physical
      connections of mitochondria within the cell. Here, we described a new and
      efficient protocol to analyze the mitochondrial respiratory states in BAT
      biopsies that relies on intracellular triglyceride depletion followed by tissue
      permeabilization. In addition to minimizing tissue requirements to ~17 mg wet
      weight, the proposed protocol enabled analysis of all mitochondrial respiratory
      states, including phosphorylation (OXPHOS), no-phosphorylation (LEAK), and
      uncoupled (ETS) states, as well as the use of substrates for complex I, complex
      II, and cytochrome c; together, these features demonstrated mitochondrial
      integrity and validated the preparation efficacy. Therefore, the protocol
      described here increases the possibilities of answering physiological questions
      related to small BAT regions of human and animal models, which shall help to
      unravel the mechanisms that regulate mitochondrial function in health and
      disease.

PMID- 27717858
TI  - Poverty and prevalence of antimicrobial resistance in invasive isolates.
AB  - OBJECTIVES: To evaluate the association between the income status of a country
      and the prevalence of antimicrobial resistance (AMR) in the three most common
      bacteria causing infections in hospitals and in the community: third-generation
      cephalosporin (3GC)-resistant Escherichia coli, methicillin-resistant
      Staphylococcus aureus (MRSA), and 3GC-resistant Klebsiella species. METHODS:
      Using 2013-2014 country-specific data from the ResistanceMap repository and the
      World Bank, the association between the prevalence of AMR in invasive samples and
      the gross national income (GNI) per capita was investigated through linear
      regression with robust standard errors. To account for non-linear association
      with the dependent variable, GNI per capita was log-transformed. RESULTS: The
      models predicted an 11.3% (95% confidence interval (CI) 6.5-16.2%), 18.2% (95% CI
      11-25.5%), and 12.3% (95% CI 5.5-19.1%) decrease in the prevalence of 3GC
      resistant E. coli, 3GC-resistant Klebsiella species, and MRSA, respectively, for
      each log GNI per capita. The association was stronger for 3GC-resistant E. coli
      and Klebsiella species than for MRSA. CONCLUSIONS: A significant negative
      association between GNI per capita and the prevalence of MRSA and 3GC-resistant
      E. coli and Klebsiella species was found. These results underscore the urgent
      need for new policies aimed at reducing AMR in resource-poor settings.

PMID- 27717859
TI  - Risk factors for human helminthiases in rural Philippines.
AB  - BACKGROUND: A cross-sectional survey was performed in 2012 among 18 rural
      barangays in Northern Samar, the Philippines in order to determine the prevalence
      of single and multiple species helminth infections and the underlying risk
      factors of acquiring one or more parasites. METHODS: A total of 6976 participants
      who completed a medical questionnaire and provided a stool sample for examination
      were included in the final analysis. RESULTS: The overall prevalence rates of
      Schistosoma japonicum, Ascaris lumbricoides, Trichuris trichiura, and hookworm
      were found to be moderate to high at 28.9%, 36.5%, 61.8%, and 28.4%,
      respectively. However, the prevalence of harbouring any of the helminths was
      found to be higher at 75.6%. Significant variation was evident among the
      predicted barangay-specific random effects for infection with S. japonicum
      (barangay variance of 0.66, 95% confidence interval 0.31-1.40) and for any
      helminth infection (barangay variance of 0.63, 95% confidence interval 0.30
      1.29). The predictive models showed, with greater than 80% sensitivity and
      specificity, that low socio-economic status, low levels of education, poor
      sanitation, proximity to water sources, occupation (i.e., farming and fishing),
      and male sex were all reliable indicators of infection status. CONCLUSIONS: This
      study will aid in the targeting of limited resources for national treatment and
      WASH (water, sanitation, and hygiene) efforts in low- and middle-income
      countries.

PMID- 27717860
TI  - The Effects of Melatonin on Ethylene Glycol-induced Nephrolithiasis: Role on
      Osteopontin mRNA Gene Expression.
AB  - OBJECTIVE: To evaluate the protective effects of melatonin (Mel) on an ethylene
      glycol (EG)-induced nephrolithiasis model in rats. MATERIALS AND METHODS: Thirty
      two Wistar albino rats were divided into 4 groups: control, EG, prevention Mel
      (Mel + EG + Mel), and therapeutic Mel (EG + Mel). EG (0.75%) was added to
      drinking water to create nephrolithiasis model. The EG group received EG and the
      Mel + EG + Mel group received both EG and Mel for 8 weeks. In the EG + Mel group,
      EG is given for 8 weeks and Mel is given for the last 4 weeks of the experiment.
      At the end of experimental period, urine, blood samples, and tissues were
      collected. RESULTS: In 24-hour urine samples, calcium, citrate, and creatinine
      levels were decreased and oxalate levels were increased in the EG group, whereas
      Mel prevention and Mel treatment reversed these parameters back to control
      levels. Malondialdehyde, glutathione activities, myeloperoxidase, superoxide
      dismutase levels, and caspase-3 activity showed improvements in the Mel-treated
      groups when compared with the EG group. 8-Hydroxydeoxyguanosine, matrix
      metalloproteinase 9 levels, N-acetyl-beta-glucosaminidase activity, and
      osteopontin mRNA expression were elevated in the EG group and decreased back to
      control levels in the Mel + EG + Mel and EG + Mel groups. Histological
      examination showed improvement in the Mel-treated groups when compared with the
      EG group. CONCLUSION: Mel can prevent crystalluria and kidney damage due to
      crystal formation and aggregation. It can be considered as a potential
      prophylactic and protective agent in high-risk patients with urinary stone
      formation or recurrence if supported by further clinical studies.

PMID- 27717862
TI  - Challenges in predicting which patients will develop ARDS.

PMID- 27717863
TI  - Reply to: "Hepatitis C testing in U.S. veterans born 1945-1965: An update".

PMID- 27717864
TI  - Extensive testing or focused testing of patients with elevated liver enzymes.
AB  - BACKGROUND & AIMS: Many patients have elevated serum aminotransferases reflecting
      many underlying conditions, both common and rare. Clinicians generally apply one
      of two evaluative strategies: testing for all diseases at once (extensive) or
      just common diseases first (focused). METHODS: We simulated the evaluation of
      10,000 adult outpatients with elevated with alanine aminotransferase to compare
      both testing strategies. Model inputs employed population-based data from the US
      (National Health and Nutrition Examination Survey) and Britain (Birmingham and
      Lambeth Liver Evaluation Testing Strategies). Patients were followed until a
      diagnosis was provided or a diagnostic liver biopsy was considered. The primary
      outcome was US dollars per diagnosis. Secondary outcomes included doctor visits
      per diagnosis, false-positives per diagnosis and confirmatory liver biopsies
      ordered. RESULTS: The extensive testing strategy required the lowest monetary
      cost, yielding diagnoses for 54% of patients at $448/patient compared to 53% for
      $502 under the focused strategy. The extensive strategy also required fewer
      doctor visits (1.35 vs. 1.61 visits/patient). However, the focused strategy
      generated fewer false-positives (0.1 vs. 0.19/patient) and more biopsies (0.04
      vs. 0.08/patient). Focused testing becomes the most cost-effective strategy when
      accounting for pre-test probabilities and prior evaluations performed. This
      includes when the respective prevalence of alcoholic, non-alcoholic and drug
      induced liver disease exceeds 51.1%, 53.0% and 13.0%. Focused testing is also the
      most cost-effective strategy in the referral setting where assessments for viral
      hepatitis, alcoholic and non-alcoholic fatty liver disease have already been
      performed. CONCLUSIONS: Testing for elevated liver enzymes should be deliberate
      and focused to account for pre-test probabilities if possible. LAY SUMMARY: Many
      patients have elevated liver enzymes reflecting one of many possible liver
      diseases, some of which are very common and some of which are rare. Tests are
      widely available for most causes but it is unclear whether clinicians should
      order them all at once or direct testing based on how likely a given disease may
      be given the patient's history and physical exam. The tradeoffs of both
      approaches involve the money spent on testing, number of office visits needed,
      and false positive results generated. This study shows that if there are no clues
      available at the time of evaluation, testing all at once saves time and money
      while causing more false positives. However, if there are strong clues regarding
      the likelihood of a particular disease, limited testing saves time, money and
      prevents false positives.

PMID- 27717865
TI  - Two different analyzing methods for inhibitory reflexes: Do they yield comparable
      outcomes?
AB  - BACKGROUND: For the analysis of inhibitory reflexes, no consensus exists
      regarding the methodology that should be used. The most commonly used methods are
      the cumulative sum (CUSUM) error box and the t-test. The aim of this study was to
      assess the interexaminer reliability of those two analyzing methods and to test
      whether both methods: yield similar results. METHODS: Inhibitory jaw reflexes
      were recorded from the right masseter muscle of 11 participants (6 males, 5
      females). Electrical stimuli were applied at the hairy skin of the upper lip on
      the right side. In total, 16 stimuli were applied while the participants
      maintained their clenching level at 10% of their maximum voluntary EMG activity.
      Two different examiners analyzed the reflex data with two different methods: the
      CUSUM error box and the t-test. The outcome variables were the number of reflex
      parts, the reflex area size, and the reflex onset. Comparability between
      examiners and between the two analyzing methods: was assessed with the use of the
      intraclass correlation coefficient (ICC). RESULTS: The interexaminer reliability
      was fair-to-good to excellent for both the CUSUM error box and the t-test
      analyses and for all the variables tested. The comparability of the two analyzing
      methods: was fair-to-good. COMPARISON WITH EXISTING METHODS/CONCLUSION: When
      analyzing the inhibitory reflex data, both the CUSUM error box and the t-test can
      be used.

PMID- 27717866
TI  - Neurobasal media facilitates increased specificity of siRNA-mediated knockdown in
      primary cerebellar cultures.
AB  - BACKGROUND: Efficient and specific knockdown of proteins in post-mitotic cells
      such as differentiated neurons can be difficult to achieve. Further, special care
      must be taken to maintain the health of neurons in vitro. We wanted to achieve
      knockdown in primary cerebellar granule neurons, which can be effectively grown
      in NeurobasalTM media. NEW METHOD: We tested the efficiency of siRNA from the
      Accell range from DharmaconTM when delivered in NeurobasalTM media in contrast to
      the recommended Accell Delivery media provided by the manufacturer. RESULTS: We
      observed a more specific knockdown of target in NeurobasalTM media, than in
      Accell Delivery media when using cerebellar granule neurons. Transfection
      efficiency and cell viability was comparable between the two media. COMPARISON
      WITH EXISTING METHODS: Delivery of siRNA in NeurobasalTM media facilitates
      increased specificity of the knockdown compared to delivery in Accell Delivery
      media. The off-target effect observed in Accell Delivery media was not a
      secondary biological response to downregulation of target, but rather a mixture
      of specific and non-specific off-target effects. CONCLUSIONS: Specific knockdown
      of target can be achieved in primary cerebellar granule cells using Accell siRNAs
      in NeurobasalTM media. This method ensures specific knockdown in post-mitotic
      neurons without the need for biosafety level 2 laboratories, additional reagents,
      or instruments needed by other transfection.

PMID- 27717867
TI  - MKK3 influences mitophagy and is involved in cigarette smoke-induced
      inflammation.
AB  - Cigarette smoking is the primary risk factor for COPD which is characterized by
      excessive inflammation and airflow obstruction of the lung. While inflammation is
      causally related to initiation and progression of COPD, the mitochondrial
      mechanisms that underlie the associated inflammatory responses are poorly
      understood. In this context, we have studied the role played by Mitogen activated
      protein (MAP) kinase kinase 3 (MKK3), a dual-specificity protein kinase, in
      cigarette smoke induced-inflammation and mitochondrial dysfunction. Serum pro
      inflammatory cytokines were significantly elevated in WT but not in MKK3-/- mice
      exposed to Cigarette smoke (CS) for 2 months. To study the cellular mechanisms of
      inflammation, bone marrow derived macrophages (BMDMs), wild type (WT) and MKK3-/
      , were exposed to cigarette smoke extract (CSE) and inflammatory cytokine
      production and mitochondrial function assessed. The levels of IL-1beta, IL-6, and
      TNFalpha were increased along with higher reactive oxygen species (ROS) and P
      NFkappaB after CSE treatment in WT but not in MKK3-/- BMDMs. CSE treatment
      adversely affected basal mitochondrial respiration, ATP production, maximum
      respiratory capacity, and spare respiratory capacity in WT BMDMs only. Mitophagy,
      clearance of dysfunctional mitochondria, was up regulated in CS exposed WT mice
      lung tissue and CSE exposed WT BMDMs, respectively. The proteomic analysis of
      BMDMs by iTRAQ (isobaric tags for relative and absolute quantitation) showed up
      regulation of mitochondrial dysfunction associated proteins in WT and higher
      OXPHOS (Oxidative phosphorylation) and IL-10 signaling proteins in MKK3-/- BMDMs
      after CSE exposure, confirming the critical role of mitochondrial homeostasis.
      Interestingly, we found increased levels of p-MKK3 by immunohistochemistry in
      COPD patient lung tissues that could be responsible for insufficient mitophagy
      and disease progression. This study identifies MKK3 as a negative regulator of
      mitochondrial function and inflammatory responses to CS and suggests that MKK3
      could be a therapeutic target.

PMID- 27717868
TI  - Intermittent hypoxia confers pro-metastatic gene expression selectively through
      NF-kappaB in inflammatory breast cancer cells.
AB  - Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer.
      Treatment options are limited and the mechanisms underlying its aggressiveness
      are poorly understood. Intermittent hypoxia (IH) causes oxidative stress and is
      emerging as important regulator of tumor metastasis. Vessels in IBC tumors have
      been shown to be immature, which is a primary cause of IH. We therefore
      investigated the relevance of IH for the modulation of gene expression in IBC
      cells in order to assess IH as potential regulator of IBC aggressiveness. Gene
      array analysis of IBC cells following chronic IH (45-60 days) demonstrated
      increased expression of pro-metastatic genes of the extracellular matrix, such as
      tenascin-C (TNC; an essential factor of the metastatic niche) and matrix
      metalloproteinase 9 (MMP9), and of pro-inflammatory processes, such as
      cyclooxygenase-2 (COX-2). Investigating the oxidative stress-dependent regulation
      of TNC, we found a gradual sensitivity on mRNA and protein levels. Oxidative
      stress activated NF-E2-related factor 2 (Nrf2), c-Jun N-terminal kinase (JNK), c
      Jun and nuclear factor kappaB (NF-kappaB), but TNC upregulation was only
      dependent on NF-kappaB activation. Pharmacological inhibition of inhibitor of NF
      kappaB alpha (IkappaBalpha) phosphorylation as well as overexpression of
      IkappaBalpha prevented TNC, MMP9 and COX-2 induction, whereas the pro
      inflammatory cytokine interleukin-1beta (IL-1beta) increased their expression
      levels. Analysis of the gene array data showed NF-kappaB binding sites for 64% of
      all upregulated genes, linking NF-kappaB with IH-dependent regulation of pro
      metastatic gene expression in IBC cells. Our results provide a first link between
      intermittent hypoxia and pro-metastatic gene expression in IBC cells, revealing a
      putative novel mechanism for the high metastatic potential of IBC.

PMID- 27717870
TI  - Neonatal interventions differently affect maternal care quality and have sexually
      dimorphic developmental effects on corticosterone secretion.
AB  - Neonatal handling (H) and maternal separation (MS) both induce changes in
      maternal care, but the contribution of these changes to the behavioral and
      neurochemical outcomes of the offspring remains unclear, as studies often find
      opposite results concerning the frequency of maternal behaviors, particularly in
      the MS paradigm. In this study, behavior displayed by H, MS and non-handled (NH)
      Wistar rat dams were observed during the first 10days after birth. A tentative
      assessment of the quality of maternal care was made, using a previously reported
      score that reflects behavior fragmentation and inconsistency. Central oxytocin
      levels and hippocampal synaptic plasticity markers were also evaluated in dams,
      immediately after litter weaning. In adulthood, male and female offspring were
      subjected to a contextual stress-induced corticosterone challenge to provide
      further information on the impact of early interventions on neuroendocrine
      parameters. We found that while both H and MS interventions induced an increase
      in the amount of pup-directed behavior, MS dams displayed a more fragmented and
      inconsistent pattern of care, reflecting poorer maternal care quality.
      Interestingly, an increase in oxytocin levels was observed only in H dams. While
      H offspring did not differ from NH, MS males and females showed marked
      differences in corticosterone secretion compared to controls. Our results suggest
      that briefly removing the pups from the nest alters maternal care quantity but
      not quality and increases central oxytocin, while long separations appear to
      increase low quality maternal care and change neuroendocrine responses in adult
      offspring in a sex-specific manner.

PMID- 27717871
TI  - Effects of multiple brief exposures to trauma-associated cues on traumatized
      resilient and vulnerable rats.
AB  - Intrusive re-experiencing of a trauma is a core symptom in post-traumatic stress
      disorder (PTSD), and is often triggered by contextual cues associated with the
      event. It is not yet established if intrusive re-experiencing is the consequence
      of PTSD, or if it could contribute to the development of PTSD following a
      traumatic event. The present study (1) examined the impact of repeated brief re
      exposures to trauma reminders on the strength of PTSD-like symptoms, as well as
      on their time-development and (2) investigated the reactivity over time to these
      cues in trauma resilient and vulnerable rats, defined on the basis of the PTSD
      like symptoms they demonstrated. Rats were exposed to a Single Prolonged Stress,
      combining three different stresses (2-h restraint, 20-min forced swim and CO2
      unconsciousness) delivered together with tone and odor cues and preceded by an
      inhibitory avoidance conditioning or a control procedure. During the following
      two weeks, reminded rats were briefly re-exposed to trauma-associated cues either
      4 or 8 times. The results indicated that 4 re-exposures to the same cue
      strengthened PTSD-like symptoms (anxiety, arousal, fear to trauma-cue). However 8
      re-exposures to similar or different trauma-cues did not alter PTSD-like symptoms
      and led to a rapid extinction of the fear reactivity to these cues. The present
      results further indicated that shortly after trauma, both resilient and
      vulnerable rats strongly reacted to trauma-associated cues, while only vulnerable
      rats reacted long after the trauma, suggesting a slower loss of fear responses to
      trauma cues in these rats. We concluded that re-experiencing may participate in,
      but cannot be solely responsible for, the development of long-term PTSD effects.

PMID- 27717861
TI  - Epidemiological characteristics, practice of ventilation, and clinical outcome in
      patients at risk of acute respiratory distress syndrome in intensive care units
      from 16 countries (PRoVENT): an international, multicentre, prospective study.
AB  - BACKGROUND: Scant information exists about the epidemiological characteristics
      and outcome of patients in the intensive care unit (ICU) at risk of acute
      respiratory distress syndrome (ARDS) and how ventilation is managed in these
      individuals. We aimed to establish the epidemiological characteristics of
      patients at risk of ARDS, describe ventilation management in this population, and
      assess outcomes compared with people at no risk of ARDS. METHODS: PRoVENT
      (PRactice of VENTilation in critically ill patients without ARDS at onset of
      ventilation) is an international, multicentre, prospective study undertaken at
      119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were
      receiving mechanical ventilation in participating ICUs during a 1-week period
      between January, 2014, and January, 2015, were enrolled into the study. The Lung
      Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of
      4 or higher defining those at risk of ARDS. The primary outcome was the
      proportion of patients at risk of ARDS. Secondary outcomes included ventilatory
      management (including tidal volume [VT] expressed as mL/kg predicted bodyweight
      [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H2O),
      development of pulmonary complications, and clinical outcomes. The PRoVENT study
      is registered at ClinicalTrials.gov, NCT01868321. The study has been completed.
      FINDINGS: Of 3023 patients screened for the study, 935 individuals fulfilled the
      inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS
      (30%, 95% CI 27-33), representing 0.14 cases per ICU bed over a 1-week period. VT
      was similar for patients at risk and not at risk of ARDS (median 7.6 mL/kg PBW
      [IQR 6.7-9.1] vs 7.9 mL/kg PBW [6.8-9.1]; p=0.346). PEEP was higher in patients
      at risk of ARDS compared with those not at risk (median 6.0 cm H2O [IQR 5.0-8.0]
      vs 5.0 cm H2O [5.0-7.0]; p<0.0001). The prevalence of ARDS in patients at risk of
      ARDS was higher than in individuals not at risk of ARDS (19/260 [7%] vs 17/556
      [3%]; p=0.004). Compared with individuals not at risk of ARDS, patients at risk
      of ARDS had higher in-hospital mortality (86/543 [16%] vs 74/232 [32%];
      p<0.0001), ICU mortality (62/533 [12%] vs 66/227 [29%]; p<0.0001), and 90-day
      mortality (109/653 [17%] vs 88/282 [31%]; p<0.0001). VT did not differ between
      patients who did and did not develop ARDS (p=0.471 for those at risk of ARDS;
      p=0.323 for those not at risk). INTERPRETATION: Around a third of patients
      receiving mechanical ventilation in the ICU were at risk of ARDS. Pulmonary
      complications occur frequently in patients at risk of ARDS and their clinical
      outcome is worse compared with those not at risk of ARDS. There is potential for
      improvement in the management of patients without ARDS. Further refinements are
      needed for prediction of ARDS. FUNDING: None.

PMID- 27717869
TI  - Withaferin A induces Nrf2-dependent protection against liver injury: Role of
      Keap1-independent mechanisms.
AB  - Small molecules of plant origin offer presumptively safe opportunities to prevent
      carcinogenesis, mutagenesis and other forms of toxicity in humans. However, the
      mechanisms of action of such plant-based agents remain largely unknown. In recent
      years the stress responsive transcription factor Nrf2 has been validated as a
      target for disease chemoprevention. Withania somnifera (WS) is a herb used in
      Ayurveda (an ancient form of medicine in South Asia). In the recent past,
      withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated
      to be preventive and therapeutic against multiple diseases in experimental
      models. The goals of this study are to evaluate withanolides such as WA as well
      as Withania somnifera root extract as inducers of Nrf2 signaling, to probe the
      underlying signaling mechanism of WA and to determine whether prevention of
      acetaminophen (APAP)-induced hepatic toxicity in mice by WA occurs in an Nrf2
      dependent manner. We observed that WA profoundly protects wild-type mice but not
      Nrf2-disrupted mice against APAP hepatotoxicity. WA is a potent inducer of Nrf2
      dependent cytoprotective enzyme expression both in vivo and in vitro.
      Unexpectedly, WA induces Nrf2 signaling at least in part, in a Keap1-independent,
      Pten/Pi3k/Akt-dependent manner in comparison to prototypical Nrf2 inducers,
      sulforaphane and CDDO-Im. The identification of WA as an Nrf2 inducer that can
      signal through a non-canonical, Keap1-independent pathway provides an opportunity
      to evaluate the role of other regulatory partners of Nrf2 in the dietary and
      pharmacological induction of Nrf2-mediated cytoprotection.

PMID- 27717872
TI  - Graft Transit Time Has No Effect on Outcome of Unrelated Donor Hematopoietic Cell
      Transplants Performed in Australia and New Zealand: A Study from the Australasian
      Bone Marrow Transplant Recipient Registry.
AB  - A previous study found that platelet recovery and mortality were worse in
      recipients of myeloablative bone marrow transplants where graft transit times
      were longer than 20 hours. This retrospective study of unrelated myeloablative
      allogeneic transplantation performed within Australia and New Zealand analyzed
      transplant outcomes according to graft transit times. Of 233 assessable cases, 76
      grafts (33%) were sourced from bone marrow (BM) and 157 (67%) from peripheral
      blood. Grafts sourced from Australia and New Zealand (47% of total) were
      associated with a median transit time of 6 hours versus 32 hours for overseas
      sourced grafts (53% of total). Graft transit temperature was refrigerated in 85%,
      ambient in 6%, and unknown in 9% of cases, respectively. Graft transit times had
      no significant effect on neutrophil or platelet engraftment, treatment-related
      mortality, overall survival, and incidence of acute or chronic graft-versus-host
      disease. Separate analysis of BM grafts, although of reduced power, also showed
      no significant difference in either neutrophil or platelet engraftment or
      survival between short and longer transport times. This study gives reassurance
      that both peripheral blood stem cell and especially BM grafts subjected to long
      transit times and transported at refrigerated temperatures may not be associated
      with adverse recipient outcomes.

PMID- 27717873
TI  - Microbial signatures of oral dysbiosis, periodontitis and edentulism revealed by
      Gene Meter methodology.
AB  - Conceptual models suggest that certain microorganisms (e.g., the "red" complex)
      are indicative of a specific disease state (e.g., periodontitis); however, recent
      studies have questioned the validity of these models. Here, the abundances of
      500+ microbial species were determined in 16 patients with clinical signs of one
      of the following oral conditions: periodontitis, established caries, edentulism,
      and oral health. Our goal was to determine if the abundances of certain
      microorganisms reflect dysbiosis or a specific clinical condition that could be
      used as a 'signature' for dental research. Microbial abundances were determined
      by the analysis of 138,718 calibrated probes using Gene Meter methodology. Each
      16S rRNA gene was targeted by an average of 194 unique probes (n=25nt). The
      calibration involved diluting pooled gene target samples, hybridizing each
      dilution to a DNA microarray, and fitting the probe intensities to adsorption
      models. The fit of the model to the experimental data was used to assess
      individual and aggregate probe behavior; good fits (R2>0.90) were retained for
      back-calculating microbial abundances from patient samples. The abundance of a
      gene was determined from the median of all calibrated individual probes or from
      the calibrated abundance of all aggregated probes. With the exception of genes
      with low abundances (<2 arbitrary units), the abundances determined by the
      different calibrations were highly correlated (r~1.0). Seventeen genera were
      classified as 'signatures of dysbiosis' because they had significantly higher
      abundances in patients with periodontitis and edentulism when contrasted with
      health. Similarly, 13 genera were classified as 'signatures of periodontitis',
      and 14 genera were classified as 'signatures of edentulism'. The signatures could
      be used, individually or in combination, to assess the clinical status of a
      patient (e.g., evaluating treatments such as antibiotic therapies). Comparisons
      of the same patient samples revealed high false negatives (45%) for next
      generation-sequencing results and low false positives (7%) for Gene Meter
      results.

PMID- 27717874
TI  - Pharmaceutical development of novel lactate-based 6-fluoro-l-DOPA formulations.
AB  - 6-[18F]fluoro-l-dihydroxyphenylalanine (18F-DOPA) is a diagnostic positron
      emission tomography (PET) agent, which has been used for decades in imaging the
      loss of dopaminergic neurons in Parkinson's disease, and more recently to detect,
      stage and restage neuroendocrine tumors (NETs) and to search for recurrence of
      viable glioma tissue. The commercially available 18F-DOPA PET radiopharmaceutical
      for diagnostic use in European Union countries, is formulated in an aqueous
      solution of acetic acid (1.05mg/mL) and has the disadvantages that, immediately
      before injection, the pH must be adjusted to 4.0-5.0 by the addition of a sterile
      solution of sodium bicarbonate (84mg/mL) causing a light and transient burning
      sensation at the injection site. To overcome these drawbacks, preformulation
      studies were accomplished to confirm that F-DOPA degradation was affected by pH.
      Hence, two formulations of F-DOPA, namely ND1 and ND2, were prepared maintaining
      the pH=5.0 using 1mM l-(+)-lactate buffer, excluding oxygen, and incorporating in
      the formula the chelating agent Na2EDTA (1mM). F-DOPA oxygen exposure, the
      presence of free metal cations in formulation and high pH values seem to promote
      F-DOPA degradation. The resulting formulations proved to guarantee the chemical
      stability of F-DOPA in solution at pH5.0, value also compatible with the direct
      infusion. In vitro cell viability tests on mouse skeletal muscle fibers, renal
      tsa201 and neuronal SH-SY5Y cell lines, and in vivo studies in rats reported
      elsewhere, showed cell tolerability to the new F-DOPA formulations providing the
      basis for their further in vivo evaluation.

PMID- 27717875
TI  - Inhibition of YAP signaling contributes to senescence of hepatic stellate cells
      induced by tetramethylpyrazine.
AB  - Accumulating evidence indicates that hepatic stellate cells (HSCs) are the
      central mediators and major effectors in the development of hepatic fibrosis. It
      is well-known that regulation of cell proliferation and apoptosis are potential
      strategies to block the activation of HSCs. Recently, several studies have
      revealed that induction of HSC senescence could prevent and cure the liver
      fibrosis. In our previous work, we have demonstrated that the natural product
      tetramethylpyrazine (TMP) could inhibit the activation of HSCs and ameliorate
      hepatic fibrosis. The aim of this study was to identify a new role of TMP in the
      regulation of activated HSC senescence and to elucidate the underlying
      mechanisms. In this study, our data showed that TMP could promote HSC senescence
      in vivo and in vitro. Moreover, TMP affected the cell cycle and telomerase
      activity. We further demonstrated that P53 siRNA or P53 pharmacological inhibitor
      PFT-alpha abrogated the TMP-induced HSC senescence in vitro. Meanwhile, similar
      results were obtained in vivo. Further studies indicated that TMP promoted the
      expression of P53 through a YAP inhibition-dependent mechanism. Moreover,
      silencing YAP enhanced TMP induction of activated HSC senescence. Collectively,
      our results suggested that TMP inhibited the activation of HSCs by inducing
      senescence and had therapeutic implication for the treatment of liver fibrosis.

PMID- 27717876
TI  - Programmed death (PD)-1 attenuates macrophage activation and brain inflammation
      via regulation of fibrinogen-like protein 2 (Fgl-2) after intracerebral
      hemorrhage in mice.
AB  - Neuroinflammation plays an important role in the recovery of brain injury in ICH.
      Macrophage is the major executor in the neuroinflammation and initiates
      neurological defects. Programmed death 1 (PD-1) delivers inhibitory signals that
      regulate the balance between T cell activation, tolerance, and immunopathology.
      PD-1 expression by macrophages plays a pathologic role in the innate inflammatory
      response. However, the exact role of PD-1 on inflammatory responses following ICH
      has not been well identified. In this experiment, PD-1 KO (PD-1 -/-) ICH mice and
      Wild-type (WT) ICH mice were caused by intracranial injection of type IV
      collagenase. The level of macrophage activation, inflammatory cytokines and
      fibrinogen-like protein 2 (Fgl-2) were detected using immunofluorescence staining
      and ELISA assays. In addition, brain edema and neurological scores of ICH mice
      were also measured. Our data demonstrated that ICH promoted PD-1 expression of
      macrophage and enhanced inflammatory cytokines and Fgl-2 concentrations. PD-1 -/-
      mice exhibited significantly higher expression of the inflammatory cytokines
      which initiate Fgl-2, than did their wild-type (WT) littermates. As a result,
      macrophage activation, cerebral edema and neurological deficit scores of PD-1 -/-
      mice were higher. In conclusion, our data demonstrate that PD-1 plays a vital
      role in brain inflammation via regulation of Fgl-2 after ICH, and that
      manipulation of PD-1 might be a promising therapeutical target in ICH.

PMID- 27717877
TI  - 1,25-dihydroxyvitamin D3 down-modulates the production of proinflammatory
      cytokines and nitric oxide and enhances the phosphorylation of monocyte-expressed
      STAT6 at the recent-onset type 1 diabetes.
AB  - BACKGROUND: Type 1 diabetes (T1D) is associated with an imbalance between
      inflammation and repair. Recently, the biologically active form of vitamin D3,
      i.e. 1,25(OH)2D3, has been reported to have potent immunomodulatory effects on
      both innate and adaptive immune cells, as well as on the production of their
      specific cytokines. METHODS: We examined the effect of 1,25(OH)2D3 on the
      production of proinflammatory Th1/Th17 and anti-inflammatory Th2/Treg related
      cytokines, as well as on the phosphorylation of monocyte-expressed STAT4 and
      STAT6 at the recent-onset human T1D. RESULTS: The levels of IFN-gamma, IL-17 and
      nitric oxide (NO) production were significantly increased in peripheral blood
      mononuclear cells (PBMCs) from patients with T1D compared to controls. Similarly,
      STAT4 tyrosine phosphorylation (p-STAT4, Tyr693) levels were significantly
      increased in monocytes from patients when compared to controls. Conversely, the
      levels of IL-4, IL-10 and p-STAT6 (Tyr641) were significantly decreased in type 1
      diabetic patients than in controls. Treatment with 1,25(OH)2D3 resulted in
      significant up-regulation of IL-4, IL-10, arginase activity, and p-STAT6 and,
      conversely, down-regulation of IFN-gamma, IL-17 and NO production levels, as well
      as p-STAT4. Additionally, 1,25(OH)2D3 significantly enhanced Treg-to-Th17 ratio,
      and induced a significant decrease in Th1-to-Th2, NO production-to-arginase
      activity and p-STAT4-to-p-STAT6 ratios. CONCLUSIONS: Our study suggests that the
      biologically active form of vitamin D can reverse the activation of inflammatory
      pathways at the onset of T1D. Additionally, its immunomodulation properties may
      vary depending on the overall patterns of cytokines. From a therapeutic point of
      view, vitamin D may potentially be suggested as an immunological adjuvant and a
      potential anti-inflammatory agent in individuals at risk of T1D.

PMID- 27717878
TI  - Insights into selenite reduction and biogenesis of elemental selenium
      nanoparticles by two environmental isolates of Burkholderia fungorum.
AB  - Microorganisms capable of transforming toxic selenium oxyanions into non-toxic
      elemental selenium (Se degrees ) may be considered as biocatalysts for the
      production of selenium nanoparticles (SeNPs), eventually exploitable in different
      biotechnological applications. Two Burkholderia fungorum strains (B. fungorum
      DBT1 and B. fungorum 95) were monitored during their growth for both capacity and
      efficiency of selenite (SeO32-) reduction and elemental selenium formation. Both
      strains are environmental isolates in origin: B. fungorum DBT1 was previously
      isolated from an oil refinery drainage, while B. fungorum 95 has been enriched
      from inner tissues of hybrid poplars grown in a soil contaminated by polycyclic
      aromatic hydrocarbons. Our results showed that B. fungorum DBT1 is able to reduce
      0.5mM SeO32- to Se degrees  when cultured aerobically in liquid medium at 27
      degrees C, while B. fungorum 95 can reduce more than 1mM SeO32- to Se degrees 
      within 96h under the same growth conditions, with the appearance of SeNPs in
      cultures of both bacterial strains. Biogenic SeNPs were spherical, with pH
      dependent charge and an average hydrodynamic diameter of 170nm and 200nm
      depending on whether they were produced by B. fungorum 95 or B. fungorum DBT1,
      respectively. Electron microscopy analyses evidenced that Se nanoparticles
      occurred intracellularly and extracellularly. The mechanism of SeNPs formation
      can be tentatively attributed to cytoplasmic enzymatic activation mediated by
      electron donors. Biogenic nanoparticles were then probably released outside the
      bacterial cells as a consequence of a secretory process or cell lysis.
      Nevertheless, formation of elemental selenium nanoparticles under aerobic
      conditions by B. fungorum DBT1 and B. fungorum 95 is likely due to intracellular
      reduction mechanisms. Biomedical and other high tech sectors might exploit these
      biogenic nanoparticles in the near future, once fully characterized and tested
      for their multiple properties.

PMID- 27717879
TI  - Unravelling cortico-hypothalamic pathways regulating unconditioned fear-induced
      antinociception and defensive behaviours.
AB  - The medial prefrontal cortex can influence unconditioned fear-induced defensive
      mechanisms organised by diencephalic neurons that are under tonic GABAergic
      inhibition. The posterior hypothalamus (PH) is involved with anxiety- and panic
      attack-like responses. To understand this cortical mediation, our study
      characterised anterior cingulate cortex (ACC)-PH pathways and investigated the
      effect of ACC local inactivation with lidocaine. We also investigated the
      involvement of PH ionotropic glutamate receptors in the defensive behaviours and
      fear-induced antinociception by microinjecting NBQX (an AMPA/kainate receptor
      antagonist) and LY235959 (a NMDA receptor antagonist) into the PH. ACC
      pretreatment with lidocaine decreased the proaversive effect and antinociception
      evoked by GABAA receptor blockade in the PH, which suggests that there may be
      descending excitatory pathways from this cortical region to the PH.
      Microinjections of both NBQX and LY235959 into the PH also attenuated defensive
      and antinociceptive responses. This suggests that the blockade of AMPA/kainate
      and NMDA receptors reduces the activity of glutamatergic efferent pathways. Both
      inputs from the ACC to the PH and glutamatergic hypothalamic short links
      disinhibited by intra-hypothalamic GABAA receptors blockade are potentially
      implicated. Microinjection of a bidirectional neurotracer in the PH showed a Cg1
      PH pathway and PH neuronal reciprocal connections with the periaqueductal grey
      matter. Microinjections of an antegrade neurotracer into the Cg1 showed axonal
      fibres and glutamatergic vesicle-immunoreactive terminal boutons surrounding both
      mediorostral-lateroposterior thalamic nucleus and PH neuronal perikarya. These
      data suggest a critical role played by ACC-PH glutamatergic pathways and
      AMPA/kainate and NMDA receptors in the panic attack-like reactions and
      antinociception organised by PH neurons.

PMID- 27717880
TI  - 3-Furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of the alpha7
      nicotinic receptor, reverses schizophrenia-like cognitive and social deficits in
      rats.
AB  - The cognitive impairments and negative symptoms experienced by schizophrenia
      patients still await effective treatment. Alpha7 nicotinic acetylcholine
      receptors (alpha7 nAChRs) have gain considerable attention in this regard. It has
      been recently proposed that positive allosteric modulators (PAMs) of alpha7
      nAChRs may represent an alternative strategy to that based on orthosteric
      agonists. The aim of the present study is to evaluate the efficacy of PAM-2 (3
      furan-2-yl-N-p-tolyl-acrylamide) against cognitive deficits and negative-like
      symptoms in a rat model of schizophrenia based on administration of ketamine, a
      NMDAR antagonist. The activity of PAM-2 was compared to that elicited by DMXBA,
      an alpha7 nAChR partial agonist. For this purpose, the attentional set-shifting
      task (ASST) and the novel object recognition task (NORT) were used. The
      efficacies of PAM-2 and DMXBA against ketamine-induced social withdrawal were
      assessed using the social interaction test (SIT). The results demonstrated that
      PAM-2 and DMXBA ameliorated ketamine-induced cognitive impairments on the ASST
      and NORT as well as produced pro-social activities in the SIT. Moreover, the co
      administration of inactive doses of PAM-2 and antipsychotic drugs, clozapine or
      risperidone, reversed ketamine-induced deficits. The present findings provide
      further support for the concept that alpha7-PAMs could be used either alone or in
      combination with antipsychotics for schizophrenia therapy.

PMID- 27717882
TI  - Pain modulation from the brain during diabetic neuropathy: Uncovering the role of
      the rostroventromedial medulla.
AB  - Diabetic neuropathy has a profound impact in the quality of life of patients who
      frequently complain of pain. The mechanisms underlying diabetic neuropathic pain
      (DNP) are no longer ascribed only to damage of peripheral nerves. The effects of
      diabetes at the central nervous system are currently considered causes of DPN.
      Management of DNP may be achieved by antidepressants that act on serotonin (5-HT)
      uptake, namely specific serotonin reuptake inhibitors. The rostroventromedial
      medulla (RVM) is a key pain control center involved in descending pain modulation
      at the spinal cord through local release of 5-HT and plays a peculiar role in the
      balance of bidirectional control (i.e. inhibitory and facilitatory) from the
      brain to the spinal cord. This review discusses recently uncovered
      neurobiological mechanisms that mediate nociceptive modulation from the RVM
      during diabetes installation. In early phases of the disease, facilitation of
      pain modulation from the RVM prevails through a triplet of mechanisms which
      include increase in serotonin expression at the RVM and consequent rise of
      serotonin levels at the spinal cord and upregulation of local facilitatory 5HT3
      receptors, enhancement of spontaneous activity of facilitatory RVM neurons and up
      regulation of the expression of transient receptor potential vanilloid type 1
      (TRPV1) receptor. With the progression of diabetes the alterations in the RVM
      increase dramatically, with oxidative stress and neuronal death associated to
      microglia-mediated inflammation. In a manner similar to other central areas, like
      the thalamus, the RVM is likely to be a "pain generator/amplifier" during
      diabetes, accounting to increase DNP. Early interventions in DNP prevention using
      strategies that simultaneously tackle the exacerbation of 5-HT3 spinal receptors
      and of microglial RVM activity, namely those that increase the levels of anti
      inflammatory cytokines, should be considered in the future of DNP treatment.

PMID- 27717881
TI  - N-acetylaspartate supports the energetic demands of developmental myelination via
      oligodendroglial aspartoacylase.
AB  - Breakdown of neuro-glial N-acetyl-aspartate (NAA) metabolism results in the
      failure of developmental myelination, manifest in the congenital pediatric
      leukodystrophy Canavan disease caused by mutations to the sole NAA catabolizing
      enzyme aspartoacylase. Canavan disease is a major point of focus for efforts to
      define NAA function, with available evidence suggesting NAA serves as an acetyl
      donor for fatty acid synthesis during myelination. Elevated NAA is a diagnostic
      hallmark of Canavan disease, which contrasts with a broad spectrum of alternative
      neurodegenerative contexts in which levels of NAA are inversely proportional to
      pathological progression. Recently generated data in the nur7 mouse model of
      Canavan disease suggests loss of aspartoacylase function results in compromised
      energetic integrity prior to oligodendrocyte death, abnormalities in myelin
      content, spongiform degeneration, and motor deficit. The present study utilized a
      next-generation "oligotropic" adeno-associated virus vector (AAV-Olig001) to
      quantitatively assess the impact of aspartoacylase reconstitution on
      developmental myelination. AAV-Olig001-aspartoacylase promoted normalization of
      NAA, increased bioavailable acetyl-CoA, and restored energetic balance within a
      window of postnatal development preceding gross histopathology and deteriorating
      motor function. Long-term effects included increased oligodendrocyte numbers, a
      global increase in myelination, reversal of vacuolation, and rescue of motor
      function. Effects on brain energy observed following AAV-Olig001-aspartoacylase
      gene therapy are shown to be consistent with a metabolic profile observed in mild
      cases of Canavan disease, implicating NAA in the maintenance of energetic
      integrity during myelination via oligodendroglial aspartoacylase.

PMID- 27717883
TI  - Mouse models of ageing and their relevance to disease.
AB  - Ageing is a process that gradually increases the organism's vulnerability to
      death. It affects different biological pathways, and the underlying cellular
      mechanisms are complex. In view of the growing disease burden of ageing
      populations, increasing efforts are being invested in understanding the pathways
      and mechanisms of ageing. We review some mouse models commonly used in studies on
      ageing, highlight the advantages and disadvantages of the different strategies,
      and discuss their relevance to disease susceptibility. In addition to addressing
      the genetics and phenotypic analysis of mice, we discuss examples of models of
      delayed or accelerated ageing and their modulation by caloric restriction.

PMID- 27717884
TI  - Identification of bacterial pathogens from formalin-fixed, paraffin-embedded
      tissues by using 16S sequencing: retrospective correlation of results to
      clinicians' responses.
AB  - 16S sequencing on formalin-fixed, paraffin-embedded (FFPE) material has been used
      to identify bacteria when culture-based phenotyping techniques have not worked.
      The objective of this study was to determine how frequently 16S sequencing used
      in FFPE material was helpful to clinicians in the diagnosis and treatment of
      infectious diseases. Requests for testing occurred upon consultation between an
      infectious disease pathologist and a surgical pathologist or an infectious
      disease physician. A selected paraffin block from each case was referred for 16S
      sequencing. Retrospectively, we correlated clinical history and management
      decisions on 27 cases that were tested by paneubacterial 16S sequencing. Samples
      included 24 surgical specimens, 1 autopsy, and 2 cytology blocks. Seventeen (63%)
      of the 27 cases had a positive 16S sequencing. Acute inflammation was present in
      10 of these cases, and organisms were observed using special stains in 3. In 11
      (65%) of the 17 cases, clinicians considered the organism identified by 16S
      sequencing to be the cause or possible cause of the infectious process. Organisms
      included common (Citrobacter) and fastidious bacteria (Haemophilus,
      Fusobacterium). In 3 cases, clinicians changed antibiotic treatment based on the
      bacteria identified, whereas in 8 (including 2 where no organism was found),
      clinicians continued the antibiotic treatment. The use of 16S sequencing on FFPE
      identified specific bacteria even when organisms were not observed
      histopathologically. 16S results had an impact in infectious disease management
      decisions.

PMID- 27717885
TI  - Myxoid leiomyosarcoma of the uterus: a clinicopathological and
      immunohistochemical study of 10 cases.
AB  - Uterine myxoid leiomyosarcoma (MLMS) is a rare tumor that requires modified
      diagnostic criteria compared with conventional leiomyosarcoma. We analyzed the
      clinicopathological and immunohistochemical features of 10 MLMS cases from a
      single institution. Nine of 10 MLMSs showed an invasive border, and 2 of 10 had
      vascular invasion. Seven cases exhibited low-grade nuclear features, low mitotic
      counts (median, 2/10 high-power fields), and no tumor cell necrosis. They were
      all at International Federation of Gynecology and Obstetrics stage I. Two
      recurred at the vaginal vault at 38 and 61 months, respectively. In contrast, 3
      MLMSs with high-grade nuclei had a high mitotic rate (median, 12/10 high-power
      fields) and tumor cell necrosis (2/3). They were at an advanced International
      Federation of Gynecology and Obstetrics stage (IIIA-IVB). One had lung metastases
      at 6 months, and another died at 34 months. HMGA2 immunostaining was diffusely
      expressed in all MLMSs. Overexpression of p16 and IMP3 was present in 5 and 3
      cases, respectively. We conclude that an invasive tumor border and p16 and/or
      IMP3 overexpression are helpful features in the diagnosis of MLMS. HMGA2 is a
      highly sensitive and useful marker for MLMS. MLMS might have 2 possible subtypes:
      high-grade, clinically aggressive MLMS and low-grade, relatively indolent tumors.

PMID- 27717886
TI  - The interplay between intracellular progesterone receptor and PKC plays a key
      role in migration and invasion of human glioblastoma cells.
AB  - Intracellular progesterone receptors (PRs) and protein kinases C (PKCs) are known
      regulators of cancer cell proliferation and metastasis. Both PRs and PKCs are
      found overexpressed in grade IV human astrocytomas, also known as glioblastomas,
      which are the most frequent and aggressive brain tumors. In the present study, we
      investigated whether PR activation by PKC induces the migration and invasion of
      glioblastoma derived cell lines and if PKCalpha and delta isoforms are involved
      in PR activation. We observed that PKC activation with tetradecanoylphorbol
      acetate (TPA) increases the migration and invasion capacity of two human
      glioblastoma derived human cell lines (U251 MG and U87) and that the treatment
      with the PR receptor antagonist RU486 blocks these processes. Interestingly, the
      pharmacological inhibition of the isoenzymes PKCalpha and PKCdelta also resulted
      in a blocked PR transcriptional activity. Also, TPA-dependent PR activation
      increases the expression of progesterone-induced blocking factor (PIBF), a known
      PR target gene. These results hint to an existing cross-talk between PKCs and PRs
      in regulating the infiltration process of human glioblastomas.

PMID- 27717887
TI  - Emodin alleviates bleomycin-induced pulmonary fibrosis in rats.
AB  - Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with few treatment
      options and poor prognosis. Emodin, extracted from Chinese rhubarb, was found to
      be able to alleviate bleomycin (BLM)-induced pulmonary fibrosis, yet the
      underlying mechanism remains largely unknown. This study aimed to further
      investigate the effects of emodin on the inflammation and fibrosis of BLM-induced
      pulmonary fibrosis and the mechanism involved in rats. Our results showed that
      emodin improved pulmonary function, reduced weight loss and prevented death in
      BLM-treated rats. Emodin significantly relieved lung edema and fibrotic changes,
      decreased collagen deposition, and suppressed the infiltration of myofibroblasts
      [characterized by expression of alpha-smooth muscle actin (alpha-SMA)] and
      inflammatory cells (mainly macrophages and lymphocytes). Moreover, emodin reduced
      levels of TNF-alpha, IL-6, TGF-beta1 and heat shock protein (HSP)-47 in the lungs
      of BLM-treated rats. In vitro, emodin profoundly inhibited TGF-beta1-induced
      alpha-SMA, collagen IV and fibronectin expression in human embryo lung
      fibroblasts (HELFs). Emodin also inhibited TGF-beta1-induced Smad2/3 and STAT3
      activation, indicating that Smad2/3 and STAT3 inactivation mediates emodin
      induced effects on TGF-beta1-induced myofibroblast differentiation. These results
      suggest that emodin can exert its anti-fibrotic effect via suppression of TGF
      beta1 signaling and subsequently inhibition of inflammation, HSP-47 expression,
      myofibroblast differentiation and extracellular matrix (ECM) deposition.

PMID- 27717888
TI  - New intronic splicing mutation in the LMNA gene causing progressive cardiac
      conduction defects and variable myopathy.
AB  - BACKGROUND: Most of mutations in the LMNA gene are unique and have been found in
      only a few unrelated families. The clinical interpretation of new genetic
      variants, especially beyond the coding area and canonical splice sites, is
      proving to be difficult and requires advanced investigation. METHODS: This study
      included patients with progressive cardiac conduction defects with neuromuscular
      involvement. The clinical evaluation included medical history and 24-h Holter
      monitoring. The genetic evaluation included mutation screening in the LMNA gene
      by the Sanger sequence. Sanger sequencing was followed by RT-PCR of the target
      fragment of cDNA. In silico modeling was performed with CCBulder and Modeller
      software. RESULTS: The diagnosis of limb-girdle muscular dystrophy type 1B
      (LGMD1B) was established. The new intronic variant c.513+45T>G was found in the
      LMNA gene in the proband and affected daughter. The insertion of 45bp was
      confirmed in the proband's cDNA. The structural and possible functional effects
      of the aberrant protein were predicted. CONCLUSIONS: Variant c.513+45T>G in the
      LMNA gene likely translates into the longer lamin A/C proteins with additional 15
      amino acids. This variant is thought to be pathogenic. Intronic variants in the
      LMNA gene located beside canonic splice sites may be responsible for some
      genotype-negative cases with clinical phenotype of laminopathies.

PMID- 27717889
TI  - Ovar-DRB1 haplotypes *2001 and *0301 are associated with sheep growth and ewe
      lifetime prolificacy.
AB  - BACKGROUND: The major histocompatibility complex (MHC) is an organized cluster of
      tightly linked vertebrate genes with immunological and non-immunological
      functions. While the important MHC gene DRB1 has been examined in regard to many
      sheep infectious disease traits, only one study, based on microsatellite markers,
      has previously examined DRB1 and sheep production traits. Furthermore, to our
      knowledge no studies have examined DRB1 relationship with lifetime ewe
      prolificacy traits. Therefore, we analyzed association between the presence of
      DRB1 SNP haplotypes with internationally recognized standard names and production
      traits including growth and lifetime prolificacy in 370 Rambouillet, Columbia,
      and Polypay sheep. RESULTS: The DRB1 *2001 haplotype was associated with
      increased weaning and mature weights, as well as average daily gain (Sidak
      P<0.05; corrected for the number of haplotypes tested). Interestingly, the *2001
      haplotype also showed a trend toward association with increased total number of
      lifetime lambs born (Sidak P=0.084) and number of lambs born alive (Sidak
      P=0.084). In contrast, the DRB1 *0301 haplotype was associated with decreased
      mature weight (Sidak P=0.01). CONCLUSIONS: Since the *2001 haplotype was present
      in all three breeds, these results suggest there is at least one functional
      mutation in the region that influences growth and prolificacy traits that may be
      broadly present across several breeds. Furthermore, combined use of the similar
      *2001 and *0301 multi-marker haplotypes that nonetheless have opposing directions
      of production trait associations will enhance mutation discovery in this region.
      If undesirable alleles for underlying mutations can be identified, selective
      pressure against one or a small number of undesirable alleles may improve
      production with limited impact on MHC genetic diversity and infectious disease
      susceptibility.

PMID- 27717890
TI  - Mitochondrial genome of Cricetulus migratorius (Rodentia: Cricetidae): Insights
      into the characteristics of the mitochondrial genome and the phylogenetic
      relationships of Cricetulus species.
AB  - Cricetulus migratorius is widely distributed in the northwestern arid regions of
      China. Here, the complete mitochondrial genome (mitogenome) of C. migratorius is
      reported, to our knowledge, for the first time. It was found to be 16,246bp in
      length, including 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes,
      and one control region, and showed characteristics typical of the vertebrate
      mitogenome. Comparative analyses of mitogenomes of Cricetulus species showed that
      hamster mitogenomes had the same arrangement and organizational structure. The
      base composition was AT-rich for all Cricetulus species. We elaborated the PCG
      sequence and found that the main differences in the start and stop codons were in
      the ND3 gene; the most frequently used codons were AUU (Ile) and CUA (Leu), and
      the AT-content at the 3rd position was lower than that at 1st and 2nd positions
      in all Cricetulus species. The second tRNAser had lost the dihydrouridine stem
      loop structure, which is found in all Cricetulus species. We also elucidated the
      structure of the control region (the extended termination associated sequences,
      the central conserved sequences, and the conserved sequence blocks), and the
      putative origin of replication for the light strand in all Cricetulus species.
      Based on mitogenome data with four reconstructed methods, phylogenetic trees
      showed high resolution in the divergent clades within Cricetulus. The results
      indicated that Cricetulus kamensis is at basal position, and has the earliest
      split among all Cricetulus species. Cricetulus griseus and Cricetulus
      longicaudatus clustered in a subclade, and were separate from C. kamensis. As
      previous studies have shown, Tscherskia triton is part of Cricetulus with high
      support value. It is noteworthy that C. migratorius is a young species, and has a
      close relationship with Allocricetulus eversmanni within Cricetulus, which is
      closer to the subgenus Allocricetulus.

PMID- 27717891
TI  - The rs767649 polymorphism in the promoter of miR-155 contributes to the decreased
      risk for cervical cancer in a Chinese population.
AB  - Genetic variants in miRNAs have attracted more and more attention these years
      because they are capable of altering miRNA function and/or expression,
      consequently affecting downstream biological pathways and disease risk. The
      rs767649 polymorphism, locating in the promoter of miR-155, was recently reported
      to be able to alter transcriptional activity of miR-155 and relate to lung cancer
      risk. In this study, we aimed to assess the relationship between rs767649 and
      cervical cancer (CC) risk. We investigated the association of rs767649 with CC
      risk in a two-stage case-control study with 1157 cases and 1280 controls.
      Genotyping was determined with TaqMan allelic discrimination method. The results
      showed that the rs767649 TT genotype was associated with a significantly reduced
      risk of CC in both test (549 cases and 603 controls), validation (608 cases and
      677 controls) and combined sets [adjusted odds ratio (OR)=0.67, 95% confidence
      interval (CI)=0.51-0.87 for the combined set] compared with the AA/AT genotypes.
      Moreover, the association was more prominent among patients of age>49years and
      postmenopausal status (OR=0.56, 95% CI=0.38-0.83, and 0.60, 0.40-0.89,
      respectively) and patients with clinical stage I and II CC (OR=0.67, 95% CI=0.50
      0.91, and 0.60, 0.40-0.92, respectively). Further analyses showed that miR-155
      was overexpressed in the CC tissues as compared with normal tissues, suggesting
      an oncogenic role in CC. Luciferase assay indicated that the transition of A to T
      allele might lead to miR-155 downregulation at the transcriptional level. In
      conclusion, rs767649 might be a causal variant for CC susceptibility.

PMID- 27717892
TI  - Endoscopic cyclophotocoagulation for the treatment of glaucoma.
AB  - Endoscopic cyclophotocoagulation is laser treatment of the ciliary processes with
      direct visualization using a small video camera for the purpose of lowering
      intraocular pressure. It was traditionally reserved for management of refractory
      glaucoma, but is now increasingly used as an adjunct to cataract surgery in less
      advanced glaucoma. Here we present a review of the literature evaluating
      endoscopic cyclophotocoagulation's safety and efficacy in different forms of
      glaucoma with different degrees of progression.

PMID- 27717893
TI  - Education in ophthalmology over the past 60 years.
AB  - This paper summarizes the personal experience of an ophthalmologist who has been
      involved in medical education for over 60 years. With clinical experience and
      leadership positions within ophthalmology and in broad medical organizations,
      this paper chronicles the evolution of educational practice and approaches for
      over a half century.

PMID- 27717894
TI  - Plasmodium falciparum isolates from patients with uncomplicated malaria promote
      endothelial inflammation.
AB  - The ability of Plasmodium falciparum infected erythrocytes (Pf-IEs) to activate
      endothelial cells has been described; however, the interaction of the endothelium
      with Pf-IEs field isolates from patients has been less characterized. Previous
      reports have shown that isolates alter the endothelial permeability and
      apoptosis. In this study, the adhesion of 19 uncomplicated malaria isolates to
      Human Dermal Microvascular Endothelial Cells (HDMEC), and their effect on the
      expression of ICAM-1 and proinflammatory molecules (sICAM-1, IL-6, IL-8, and MCP
      1) was evaluated. P. falciparum isolates adhered to resting and TNFalpha
      activated HDEMC cells at different levels. All isolates increased the ICAM-1
      expression on the membrane (mICAM-1) of HDMEC and increased the release of its
      soluble form (sICAM-1), as well the production of IL-6, IL-8 and MCP-1 by HDMEC
      with no signs of cell apoptosis. No correlation between parasite adhesion and
      production of cytokines was observed. In conclusion, isolates from uncomplicated
      malaria can induce a proinflammatory response in endothelial cells that may play
      a role during the initial inflammatory response to parasite infection; however, a
      continuous activation of the endothelium can contribute to pathogenesis.

PMID- 27717895
TI  - Quercetin protects against hair cell loss in the zebrafish lateral line and
      guinea pig cochlea.
AB  - Eighteen supplement drugs were screened using hair cells to determine a
      protective effect against the adverse effects of neomycin by using the zebrafish
      lateral line. The zebrafish were administered the supplement drugs 1 h before
      neomycin exposure. One hour later, animals were fixed in paraformaldehyde. Dose
      response curves were generated to evaluate the protective effect on hair cells.
      The screen identified 3 supplements (quercetin, catechin and tannic acid). Three
      minutes after exposure to neomycin, increased antioxidant activity was found in
      the lateral line hair cells, as determined by the analysis of oxidative stress.
      Quercetin decreases antioxidant activity. The identified drugs were also
      investigated to determine whether they protect the cochlea against noise-induced
      hearing loss in guinea pigs. The drugs were administered via the intraperitoneal
      route in the guinea pigs 3 days before and 4 days after noise exposure. Seven
      days after noise exposure (130-dB sound pressure level for 3 h), the auditory
      brainstem response threshold shifts were assessed. We observed that the auditory
      brainstem response threshold shift was significantly less in the quercetin group
      than in the vehicle control group. The results of our study indicate that
      screening drugs using zebrafish can determine additional protective drugs for the
      inner ear.

PMID- 27717896
TI  - Proteomic and physiological analyses of wheat seeds exposed to copper and iron
      nanoparticles.
AB  - To elucidate the role of Cu and Fe NPs on the yield of wheat varieties, a gel
      free proteomic technique was used. NPs were synthesized and characterized through
      zeta potential, EDX, and SEM. Spike length, number of grains per spike, and 1000
      grain weight were increased in wheat varieties treated with 25ppm Cu and Fe NPs.
      On treatment with 25ppm Cu and Fe NPs, a total of 58, 121, and 25 proteins were
      changed in abundance in wheat seeds of galaxy-13, Pakistan-13, and NARC-11,
      respectively. In galaxy-13, exposure to Cu NPs increased proteins involved in
      starch degradation and glycolysis. Furthermore, the number of proteins related to
      starch degradation, glycolysis, and tricarboxylic acid cycle was increased in
      galaxy-13 on Fe NPs exposure. Proteins related to glycolysis and the
      tricarboxylic acid cycle was increased in Pakistan-13 and NARC-11 by Fe NPs
      exposure. The sugar content and SOD activity was increased in wheat seeds treated
      with Cu and Fe NPs. The Cu content was increased at 25ppm Cu NPs exposure in
      seeds of wheat varieties. These results suggest that Cu NPs improved stress
      tolerance in wheat varieties by mediating the process of starch degradation,
      glycolysis, and tricarboxylic acid cycle through NPs uptake.

PMID- 27717897
TI  - Comparison of learning outcomes between learning roles (spectator and actor)
      during an immersive simulation.

PMID- 27717898
TI  - Predicting postoperative morphine consumption in children.
AB  - BACKGROUND: Morphine is the most commonly used postoperative analgesic for
      moderate to severe pain in paediatric patients, but there is little research into
      predictive factors correlating with postoperative morphine consumption. METHODS:
      All patients undergoing surgery who received morphine postoperatively over eight
      months were prospectively enrolled. Data analysed included total morphine
      consumption to day 3, age, weight, type of surgery, ASA status, preoperative
      opioid administration, predicted postoperative pain intensity (according to
      French Society of Anaesthesiology and Intensive Care classification) and surgery
      duration. Two cohorts were constructed: the first over 6months to construct a
      statistical model and the second over 2months to validate the model. ANOVA
      univariate analyses and multivariate linear analysis were performed. RESULTS: One
      hundred and fifty-three patients were included in the construct cohort and 40 in
      the validation cohort. Multivariate analysis demonstrated that total morphine
      consumption through postoperative day 3 was independently increased by a
      decreased age, female gender, an increased duration of surgery and an increased
      morphine titration in PACU. Overall, the model explained 57% of morphine
      requirement variability. When the model was applied to the validation cohort, a
      significant correlation was demonstrated between observed and predicted values:
      r=0.67, P<0.0001. CONCLUSION: Age, gender, duration of surgery and doses of
      titrated morphine in PACU proved to be strong predictors of postoperative
      morphine consumption by day 3 during paediatric surgery. Knowledge of such
      factors may help clinicians to better manage postoperative pain in children.

PMID- 27717899
TI  - Postoperative complications after craniotomy for brain tumor surgery.
AB  - INTRODUCTION: After elective craniotomy for brain tumour surgery, patients are
      usually admitted to an intensive care unit (ICU) for monitoring. Our goal was to
      evaluate the incidence and timing of neurologic and non-neurologic postoperative
      complications after brain tumour surgery, to determine factors associated with
      neurologic events and to evaluate the timing and causes of ICU readmission.
      PATIENTS AND METHODS: This prospective, observational and analytic study enrolled
      188 patients admitted to the ICU after brain tumour surgery. All postoperative
      clinical events during the first 24hours were noted and classified. Readmission
      causes and timing were also analysed. RESULTS: Twenty-one (11%) of the patients
      were kept sedated after surgery; the remaining 167 patients were studied. Thirty
      one percent of the patients presented at least one complication (25% with
      postoperative nausea and vomiting (PONV), 16% with neurologic complications). The
      occurrence of neurological complications was significantly associated with the
      absence of preoperative motor deficit and the presence of higher intraoperative
      bleeding. Seven patients (4%) were readmitted to the ICU after discharge; 43%
      (n=3) of them had a posterior fossa surgery. CONCLUSION: Postoperative
      complications, especially PONV, are frequent after brain tumour surgery.
      Moreover, 16% of patients presented a neurological complication, probably
      justifying the ICU postoperative stay for early detection. The absence of
      preoperative motor deficit and intraoperative bleeding seems to predict
      postoperative neurologic complications. Finally, patients may present
      complications after ICU discharge, especially patients with fossa posterior
      surgery, suggesting that ICU hospitalization may be longer in this type of
      surgery.

PMID- 27717900
TI  - Identification of a C-type lectin from tilapia (Oreochromis niloticus) and its
      functional characterization under low-temperature stress.
AB  - C-type lectin, which plays an important role in fish innate immunity, was cloned
      from tilapia and its functional characterization under low-temperature stress is
      reported. Its ORF is 453 bp, encoding 150 amino acids, and has a 5'UTR of 83 bp,
      a 3'UTR of 559 bp, and a poly (A) tail. The tilapia C-type lectin genomic DNA was
      acquired with a length of 5714 bp, containing six exons and five introns. Its
      promoter sequence was cloned and has a length of 2251 bp. The highest promoter
      activity occurs in the regulatory region (-900 bp to -450 bp). A hemagglutination
      assay of recombinant tilapia C-type lectin protein showed positive
      hemagglutination of rabbit and tilapia erythrocytes. RT-qPCR and western blot
      assays showed that its expression in the liver, spleen, and intestine were
      clearly affected by low-temperature stress. Thus, tilapia C-type lectin appear to
      be affected by abiotic stress, as well as by biological stress.

PMID- 27717901
TI  - Molecular characterization, expression analysis, and bactericidal activity of the
      derivative peptides of TFPI-1 and TFPI-2 in half-smooth tongue sole, Cynoglossus
      semilaevis.
AB  - Tissue factor pathway inhibitors (TFPIs) are Kunitz-type serine protease
      inhibitors that reversibly regulate the blood coagulation induced by tissue
      factor. TFPI family contain two members, TFPI-1 and TFPI-2. Recent studies have
      shown TFPI-1 and TFPI-2 also play important roles in innate immunity, however,
      the potential function of teleost TFPI are very limited. In this study, we
      characterized two TFPI (CsTFPI-1 and CsTFPI-2) molecules from half-smooth tongue
      sole (Cynoglossus semilaevis), examined their tissue distributions and expression
      patterns under pathogens stimulation as well as investigated the antibacterial
      activity of the C-terminal peptides. Quantitative real time RT-PCR analysis
      showed that constitutive CsTFPI-1 expression occurred, in increasing order, in
      head kidney, intestine, brain, spleen, liver, skin, gills, heart, and muscle;
      CsTFPI-2 was expressed, in increasing order, in the gills, intestine, skin, head
      kidney, liver, brain, spleen, muscle, and heart. Under Vibrio anguillarum,
      Streptococcus agalactiae and fish megalocytivirus stimulation, both CsTFPI-1 and
      CsTFPI-2 expression increased significantly in a manner that depended on the
      pathogen, tissue type, and infection stage, which suggested CsTFPI-1 and CsTFPI-2
      play important roles in anti-bacterial and anti-viral infection. Finally, C
      terminal peptides of CsTFPI-1 and CsTFPI-2, were synthesized and proved to have
      antibacterial effect against Micrococcus luteus that were independent of host
      serum. Take together, these results indicate that CsTFPI-1 and CsTFPI-2 play
      important roles in antimicrobial immunity of this fish.

PMID- 27717902
TI  - Mx1 of black carp functions importantly in the antiviral innate immune response.
AB  - Mx (myxovirus resistance) is an important antiviral protein in the innate immune
      responses of vertebrates to microbial pathogens. In this study, we cloned and
      characterized Mx1 of black carp (Mylopharyngodon piceus). The full-length cDNA of
      black carp Mx1 (bcMx1) consists of 2781 nucleotides and the predicted bcMx1
      protein contains 631 amino acids. bcMx1 contains a GTPase domain at the N
      terminnus, a "central interactive domain" in the middle and a GTPase effector
      domain at the C-terminus. bcMx1 mRNA was constitutively transcribed in all
      tissues tested, including the heart, liver, spleen, kidney, intestine, muscle,
      skin and gill; and bcMx1 mRNA levels increased in all but the gill after grass
      carp reovirus (GCRV) or viraemia of carp virus (SVCV) infection. Quantitative PCR
      analysis of Mylopharyngodon piceus fin (MPF) cells indicated that bcMx1 mRNA
      levels increased after GCRV or SVCV infection at different multiplicities of
      infection (MOI). Western blotting demonstrated that the molecular weight of bcMx1
      is ~75 kDa and immunofluorescent staining data of both HeLa cells and EPC cells
      showed that bcMx1 is a cytosolic protein. EPC cells transfected with plasmid
      expressing bcMx1 showed increased antiviral activity against SVCV and GCRV. All
      our data suggest that bcMx1 is an antiviral protein in the innate immune response
      of the black carp.

PMID- 27717903
TI  - An isoflavonoid-enriched extract from Pueraria lobata (kudzu) root protects human
      umbilical vein endothelial cells against oxidative stress induced apoptosis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Reactive oxygen species (ROS) mediate vascular
      cell dysfunction and lead to atherosclerosis and other chronic cardiovascular
      diseases. The root of Pueraria lobata (Willd.) Ohwi, also known as kudzu or Gegen
      (Chinese name), is one of the most important herbs in traditional Chinese
      medicine and has been widely used in the treatment of cardiovascular diseases,
      diabetes, osteonecrosis and neurodegradation diseases. In this study, an ethanol
      extract from kudzu root was prepared and the in vitro protective effect of the
      kudzu root extract (KUD) on human umbilical vein endothelial cells (HUVECs) was
      investigated. MATERIAL AND METHODS: An ethanol extract of dried kudzu root was
      purified with an AB-8 resin column, and the concentrations of puerarin, daidzin
      and daidzein in the KUD were determined using UV spectroscopy. HUVECs were
      pretreated with various concentrations of the KUD with or without rotenone and
      the viability was assessed by AlamarBlue cell viability assay. Next, HUVECs were
      pretreated with the KUD and then treated with rotenone, and the levels of ROS
      generation, apoptosis, and changes of the mitochondrial membrane potential
      (DeltaPsim) in HUVECs were measured using fluorescent staining assay and high
      content analysis. RESULTS: The contents of three major isoflavonoids (puerarin,
      daidzin and daidzein) were enriched by 7.75-27.51 fold in the extract. The KUD
      enhanced the proliferation of HUVECs, and protected HUVECs against rotenone
      induced oxidative stress and apoptosis. Additionally, the KUD prevented the loss
      of DeltaPsim in HUVECs stimulated by oxidative stress. CONCLUSION: We
      demonstrated that an isoflavonoid-rich extract prepared from kudzu root has the
      potential to act as a protector for vascular endothelial cells against
      intracellular ROS mediated apoptosis and mitochondrial damage.

PMID- 27717905
TI  - Anti-giardia activity and acute toxicity of a methanol extract of Senna racemosa
      bark.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Senna racemosa (Mill.) H.S. Irwin & Barneby (syn.
      Cassia racemosa Mill.) is a plant used in traditional Mayamedicinal practices to
      treat diarrhea. A methanol extract of S. racemosa bark has been shown to have in
      vitro activity against Giardia intestinalis. No studies of its efficacy and
      toxicity in in vivo models have been done. The present study objective was to
      analyze the activity of this methanol extract of S. racemosa bark against Giardia
      intestinalis trophozoites in experimentally infected mice, and evaluate its
      toxicological effects in rats. MATERIAL AND METHODS: S. racemosa was collected in
      Merida, Yucatan, Mexico (21 degrees 58'N, 89 degrees 36'W) in June 2005. The bark
      methanol extract was obtained and high performance liquid chromatography (HPLC
      DAD) was used to generate a constituent profile. In vivo anti-giardia activity
      was assayed with an experimental model of G. intestinalis infection in neonatal
      CD-1 mice. Nine doses ranging from 0.25-15mg extract/kg body weight were tested
      to determine the dose required to kill 50% of the trophozoites (ED50). An acute
      toxicity assay was run in which one of four single doses (200, 1000, 2000
      and3000mg/kg body weight) was orally administered to adult Wistar rats. Animal
      weight, death rates, toxic effects and behavioral parameters were observed over a
      14-d period. They were then euthanized and a necropsy performed. RESULTS: The S.
      racemosa bark extract inhibited growth of G. intestinalis (ED50=1.14mg/Kg) in
      neonatal CD-1 mice. No toxic or lethal effects were observed even at the highest
      dosage (3000mg/Kg), and neither were signs of toxicity observed in internal
      organs. The active compounds chrysophanol and physcion were present in the
      extract at a 1.76 ratio. CONCLUSIONS: The results strongly support traditional
      use of S. racemosa bark for treatment of diarrhea caused by Giardia intestinalis
      infection.

PMID- 27717904
TI  - Protective effects of seed melon extract on CCl4-induced hepatic fibrosis in
      mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus lanatus ssp. vulgaris var.
      megalaspermus Lin et Chao, was also known as watermelon belongs to family
      Cucurbitaceae, variously used as healthy food and in the treatment of liver and
      lungs problems. Currently, Citrullus lanatus has become a major economic crop of
      medicinal and edible effects with regional characteristics. AIM: This study was
      designed to evaluate the hepatoprotective and antioxidant activity of the seed
      melon (Citrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao) extract
      (SME) against carbon tetrachloride (CCl4) induced hepatic fibrosis in mice.
      MATERIALS AND METHODS: In this study, mice were randomly divided into 7 groups,
      including normal control, model, silymarin tablets as the positive control, SME
      100, 200, 400, and 800mg/kg. After 8 weeks, activities of serum alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG),
      hyaluronic acid (HA) and laminin (LN) were checked. The levels of antioxidant
      enzymes such as superoxide dismutase (SOD), glutataion (GSH) and glutathione
      peroxidase (GSH-Px) were determined after SME administration. The hydroxyproline
      (HYP) levels, malondialdehyde (MDA) levels and histopathologic examinations of
      hepatocyte fibrosis were also determined. Additionally, effects of SME on alpha
      smooth muscle actin (alpha-SMA) and transforming growth factor beta-1(TGF-beta1)
      protein expressions were determined. RESULTS: We found that SME could
      significantly lower the serum levels of hepatic enzyme markers AST, ALT, HA and
      LN (P<0.01). Compared with the CCl4-only treatment group, levels of hepatic SOD
      and GSH-Px were significantly increased, and the MDA levels were remarkably
      decreased in mice treated by SME at medium dose (400mg/kg) and high dose
      (800mg/kg) (P<0.01). A histological examination of the liver showed that lesions,
      including necrosis, lymphocyte infiltration and fatty degeneration, were
      partially healed by treatment with SME. The results of protein expressions
      studies displayed that SME could inhibit alpha-SMA and TGF-beta1 protein
      expression (P<0.01). CONCLUSION: The present results suggested that protective
      effect of SME against CCl4-induced hepatic fibrosis may rely on its effect on
      reducing oxidative stress and improving drug metabolizing enzyme activity in
      liver.

PMID- 27717906
TI  - Evaluation of wound healing property of Caesalpinia mimosoides Lam.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia mimosoides Lam. is one of the
      important traditional folk medicinal plants in the treatment of skin diseases and
      wounds used by healers of Uttara Kannada district of Karnataka state (India).
      However scientific validation of documented traditional knowledge related to
      medicinal plants is an important path in current scenario to fulfill the
      increasing demand of herbal medicine. AIM OF THE STUDY: The study was carried out
      to evaluate the claimed uses of Caesalpinia mimosoides using antimicrobial, wound
      healing and antioxidant activities followed by detection of possible active bio
      constituents. MATERIALS AND METHODS: Extracts prepared by hot percolation method
      were subjected to preliminary phytochemical analysis followed by antimicrobial
      activity using MIC assay. In vivo wound healing activity was evaluated by
      circular excision and linear incision wound models. The extract with significant
      antimicrobial and wound healing activity was investigated for antioxidant
      capacity using DPPH, nitric oxide, antilipid peroxidation and total antioxidant
      activity methods. Total phenolic and flavonoid contents were also determined by
      Folin-Ciocalteu, Swain and Hillis methods. Possible bio-active constituents were
      identified by GC-MS technique. RP-UFLC-DAD analysis was carried out to quantify
      ethyl gallate and gallic acid in the plant extract. RESULTS: Preliminary
      phytochemical analysis showed positive results for ethanol and aqueous extracts
      for all the chemical constituents. The ethanol extract proved potent
      antimicrobial activity against both bacterial and fungal skin pathogens compared
      to other extracts. The efficacy of topical application of potent ethanol extract
      and traditionally used aqueous extracts was evidenced by the complete re
      epithelization of the epidermal layer with increased percentage of wound
      contraction in a shorter period. However, aqueous extract failed to perform a
      consistent effect in the histopathological assessment. Ethanol extract showed
      effective scavenging activity against DPPH and nitric oxide free radicals with an
      expressive amount of phenolic and moderate concentration of flavonoid contents.
      Ethyl gallate and gallic acid were found to be the probable bio-active compounds
      evidenced by GCMS and RP-UFLC-DAD analysis. CONCLUSION: The study revealed the
      significant antimicrobial, wound healing and antioxidant activities of tender
      parts of C. mimosoides and proved the traditional folklore knowledge.

PMID- 27717909
TI  - Silvering and swimming effects on aerobic metabolism and reactive oxygen species
      in the European eel.
AB  - Silvering, the last metamorphosis in the eel life cycle induces morphological and
      physiological modifications in yellow eels (sedentary stage). It pre-adapts them
      to cope with the extreme conditions they will encounter during their 6000-km
      spawning migration. A previous study showed that silver eels are able to cope
      with reactive oxygen species (ROS) over-production linked to an increase in
      aerobic metabolism during sustained swimming, but the question remains as to
      whether this mechanism is associated with silvering. A sustained swimming session
      decreased red muscle in vitro mitochondrial oxygen consumption (MO2) but
      increased ROS production in both eel stages. The swimming exercise used here was
      perhaps too intense to induce a stimulation of mitochondrial function or
      biogenesis even when antioxidant enzyme activities were unchanged. Pro
      oxidant/antioxidant imbalance by lipid peroxidation increased in yellow but
      significantly decreased in silver eels. The silvering process therefore appears
      to allow a pre-adaptation of red muscle radical metabolism to the demands of
      spawning migration.

PMID- 27717907
TI  - Standardization of the manufacturing procedure for Pinelliae Rhizoma Praeparatum
      cum Zingibere et Alumine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pinelliae Rhizoma (PR), the dried tuber of
      Pinellia ternata (Thunb.) Breit., is a traditional Chinese medicinal herb. It is
      commonly used for treating cancer, cough and phlegm. To treat cancer, Chinese
      medicine practitioners often use raw PR; while to treat cough and phlegm, they
      usually use Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRZA, raw PR
      processed with ginger juice and alumen as adjuvant materials). Currently, the
      producing protocol of PRZA varies greatly among different places in China. This
      study aims to standardize the manufacturing procedure for PRZA. We also evaluated
      the impact of processing on the bioactivities and chemical profile of raw PR.
      MATERIALS AND METHODS: We used the orthogonal design to optimize the
      manufacturing procedure of PRZA at bench scale, and validated the optimized
      procedure in pilot-scale production. The MTT assay was used to compare the
      cytotoxicities of raw PR and PRZA in hepatocellular carcinoma HepG2 cells. Animal
      models (ammonia liquor-induced cough model and phenol red secretion model) were
      used to compare the antitussive and expectorant effects of raw PR and PRZA,
      respectively. The chemical profiles of raw PR and PRZA samples were compared
      using a newly developed ultra-performance liquid chromatography/quadrupole-time
      of-flight mass spectrometry (UPLC/Q-TOF-MS) method. RESULTS: The standardized
      manufacturing procedure for PRZA is as follows: soak raw PR in water until the
      center of the cut surface is devoid of a dry core, after that, boil the herb in
      water (for each 100kg raw PR, 12.5kg alumen and 25L freshly squeezed ginger juice
      are added) for 6h, and then take out and dry them. The cytotoxicity of PRZA was
      less potent than that of raw PR. Intragastric administration of raw PR or PRZA
      demonstrated antitussive and expectorant effects in mice. These effects of PRZA
      were more potent than that of raw PR at the dose of 3g/kg. By comparing the
      chemical profiles, we found that six peaks were lower, while nine other peaks
      were higher in PRZA than in raw PR. Six compounds corresponding to six individual
      changed peaks were tentatively identified by matching with empirical molecular
      formulae and mass fragments. CONCLUSION: The manufacturing procedure for PRZA was
      standardized. This protocol can be used for PRZA industrial production. The
      bioactivity assay results of raw PR and PRZA (produced using the standardized
      protocol) support the common practice for the clinical applications of these two
      decoction pieces. Moreover, raw PR and PRZA showed different chemical profiles.
      Further studies are warranted to establish the relationship between the
      alteration of chemical profiles and the changes of medicinal properties caused by
      processing.

PMID- 27717908
TI  - Actions of water extract from Cordyceps militaris in hyperuricemic mice induced
      by potassium oxonate combined with hypoxanthine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps militaris was recorded in the classic
      traditional Chinese medicine book with the main functions of "protecting liver
      and enhancing kidney functions", influencing serum uric acid levels. AIM OF
      STUDY: The aim is to investigate the hypouricemic effects and possible mechanism
      of C. militaris in hyperuricemic mice. MATERIALS AND METHODS: A water extract
      (WECM) was prepared by decocting C. militaris directly at 80  degrees C in water
      bath, followed by lyophilization. WECM at 50, 100 and 200mg/kg was orally
      administered to hyperuricemic mice induced by potassium oxonate and hypoxanthine
      combinedly and allopurinol (5mg/kg) was served as a positive control. RESULTS:
      WECM exhibited excellent hypouricemic activity, which could decrease the serum
      uric acid levels of the hyperuricemic mice (306MUmol/L) to 189, 184 and
      162MUmol/L at different doses respectively (P<0.01), approaching the levels of
      normal mice (184MUmol/L). The urate transporter 1 (URAT1) protein levels of
      kidney at different doses of WECM were 28.15, 17.43, 9.03pg/mL respectively, much
      lower than that in the hyperuricemia group (93.45pg/mL, P<0.01); and suggested
      WECM may interact with URAT1. Docking simulations using modeled structure of
      URAT1 suggested that LYS145, ARG325, ARG477 and ASP168 of URAT1 are key
      functional residues of URAT1. Four active compounds in C. militaris were
      identified and their interaction energies with target were estimated between -200
      and -400kcal/mol. CONCLUSIONS: These findings suggested that C. militaris
      produced significant hypouricemic actions and the hypouricemic effects of WECM
      may be attributed to the inhibitive effect of WECM on URAT1 protein levels. The
      results of blood urine nitrogen and serum creatinine levels and liver, kidney and
      spleen coefficients showed that WECM have no negative impacts on liver, renal and
      spleen functions. The screened four active compounds using molecular docking
      method deserve further investigation in other work.

PMID- 27717910
TI  - A case of constitutional trisomy 3 mosaicism in a teenage patient with mild
      phenotype.
AB  - Constitutional mosaicism for trisomy 3 is extremely rare, with only a few
      postnatally diagnosed cases reported in the literature. We report a case of
      constitutional trisomy 3 mosaicism in a 16-year-old female, who presented with
      chronic joint pain, easy bruising, joint hypermobility and dysmorphic features,
      including long, thin facies, over-folded dysplastic ears, and Pierre-Robin
      sequence (PRS) with cleft palate. The patient was small at birth, had cleft
      palate repair, developed chronic joint pain at age 12, and has a history of mild
      leukopenia and mild thrombocytopenia. Microarray analysis was consistent with a
      mosaic gain of an entire chromosome 3. FISH analysis of peripheral blood and
      buccal cells showed the presence of the supernumerary chromosome 3 in a low
      percentage of cells in both tissues, suggesting that the nondisjunction event
      occurred prior to the germ cell layer differentiation. Since trisomy 3 has been
      observed somatically in lymphoma, a Hematology/Oncology consultation was provided
      for the patient. The oncologist's evaluation for malignancy was unremarkable. A
      review of findings from other trisomy 3 patients reported in the literature
      reveals a diverse phenotypic spectrum and does not show a correlation between the
      proportion of abnormal cells observed in peripheral blood and the patients'
      clinical features or severity. This case demonstrates that the clinical
      presentation of an individual with trisomy 3 is highly individualized and the
      clinical course is difficult to predict.

PMID- 27717911
TI  - Fibrin structural and diffusional analysis suggests that fibers are permeable to
      solute transport.
AB  - : Fibrin hydrogels are promising carrier materials in tissue engineering. They
      are biocompatible and easy to prepare, they can bind growth factors and they can
      be prepared from a patient's own blood. While fibrin structure and mechanics have
      been extensively studied, not much is known about the relation between structure
      and diffusivity of solutes within the network. This is particularly relevant for
      solutes with a size similar to that of growth factors. A novel methodological
      approach has been used in this study to retrieve quantitative structural
      characteristics of fibrin hydrogels, by combining two complementary techniques,
      namely confocal fluorescence microscopy with a fiber extraction algorithm and
      turbidity measurements. Bulk rheological measurements were conducted to determine
      the impact of fibrin hydrogel structure on mechanical properties. From these
      measurements it can be concluded that variations in the fibrin hydrogel structure
      have a large impact on the rheological response of the hydrogels (up to two
      orders of magnitude difference in storage modulus) but only a moderate influence
      on the diffusivity of dextran solutes (up to 25% difference). By analyzing the
      diffusivity measurements by means of the Ogston diffusion model we further
      provide evidence that individual fibrin fibers can be semi-permeable to solute
      transport, depending on the average distance between individual protofibrils.
      This can be important for reducing mass transport limitations, for modulating
      fibrinolysis and for growth factor binding, which are all relevant for tissue
      engineering. STATEMENT OF SIGNIFICANCE: Fibrin is a natural biopolymer that has
      drawn much interest as a biomimetic carrier in tissue engineering applications.
      We hereby use a novel combined approach for the structural characterization of
      fibrin networks based on optical microscopy and light scattering methods that can
      also be applied to other fibrillar hydrogels, like collagen. Furthermore, our
      findings on the relation between solute transport and fibrin structural
      properties can lead to the optimized design of fibrin hydrogel constructs for
      controlled release applications. Finally, we provide new evidence for the fact
      that fibrin fibers may be permeable for solutes with a molecular weight
      comparable to that of growth factors. This finding may open new avenues for
      tailoring mass transport properties of fibrin carriers.

PMID- 27717912
TI  - Improving the fatigue performance of porous metallic biomaterials produced by
      Selective Laser Melting.
AB  - : This paper provides new insights into the fatigue properties of porous metallic
      biomaterials produced by additive manufacturing. Cylindrical porous samples with
      diamond unit cells were produced from Ti6Al4V powder using Selective Laser
      Melting (SLM). After measuring all morphological and quasi-static properties,
      compression-compression fatigue tests were performed to determine fatigue
      strength and to identify important fatigue influencing factors. In a next step,
      post-SLM treatments were used to improve the fatigue life of these biomaterials
      by changing the microstructure and by reducing stress concentrators and surface
      roughness. In particular, the influence of stress relieving, hot isostatic
      pressing and chemical etching was studied. Analytical and numerical techniques
      were developed to calculate the maximum local tensile stress in the struts as
      function of the strut diameter and load. With this method, the variability in the
      relative density between all samples was taken into account. The local stress in
      the struts was then used to quantify the exact influence of the applied post-SLM
      treatments on the fatigue life. A significant improvement of the fatigue life was
      achieved. Also, the post-SLM treatments, procedures and calculation methods can
      be applied to different types of porous metallic structures and hence this paper
      provides useful tools for improving fatigue performance of metallic biomaterials.
      STATEMENT OF SIGNIFICANCE: Additive Manufacturing (AM) techniques such as
      Selective Laser Melting (SLM) are increasingly being used for producing
      customized porous metallic biomaterials. These biomaterials are regularly used
      for biomedical implants and hence a long lifetime is required. In this paper, a
      set of post-built surface and heat treatments is presented that can be used to
      significantly improve the fatigue life of porous SLM-Ti6Al4V samples. In
      addition, a novel and efficient analytical local stress method was developed to
      accurately quantify the influence of the post-built treatments on the fatigue
      life. Also numerical simulation techniques were used for validation. The
      developed methods and techniques can be applied to other types of porous
      biomaterials and hence provide new and useful tools for improving and predicting
      the fatigue life of porous biomaterials.

PMID- 27717913
TI  - Surface phosphonation enhances hydroxyapatite coating adhesion on
      polyetheretherketone and its osseointegration potential.
AB  - : Polyetheretherketone (PEEK) has excellent mechanical properties,
      biocompatibility, chemical resistance and radiolucency, making it suitable for
      use as orthopedic implants. However, its surface is hydrophobic and bioinert, and
      surface modification is required to improve its bioactivity. In this work, we
      showed that grafting phosphonate groups via diazonium chemistry enhances the
      bioactivity of PEEK. Decreased contact angle indicated reduced hydrophobicity as
      a result of the treatment and X-ray photoelectron spectroscopy (XPS) confirmed
      the attachment of phosphonate groups to the surface. The surface treatment not
      only accelerated hydroxyapatite (HA) deposition after immersion in simulated body
      fluid but also significantly increased the adhesion strength of HA particles on
      PEEK. MC3T3-E1 cell viability, metabolic activity and deposition of calcium
      containing minerals were also enhanced by the phosphonation. After three months
      of implantation in a critical size calvarial defect model, a fibrous capsule
      surrounded untreated PEEK while no fibrous capsule was observed around the
      treated PEEK. Instead, mineral deposition was observed in the region between the
      treated PEEK implant and underlying bone. This work introduces a simple method to
      improve the potential of PEEK-based orthopedic implants. STATEMENT OF
      SIGNIFICANCE: We have introduced phosphonate groups on the surface of PEEK
      substrates using diazonium chemistry. Our results show that the treatment not
      only increased the adhesion strength of hydroxyapatite particles deposited on
      PEEK in vitro by approximately 40% compared to unmodified PEEK, but also improved
      the metabolic activity and mineralization of MC3T3-E1 cells. When implanted in
      cranial defects in rats, the phosphonate coating enhanced the osseointegration of
      PEEK by successfully preventing the formation of a fibrous capsule and favoring
      mineral deposition between the implant and the surrounding bone. This work
      introduces a simple method to improve the potential of PEEK-based orthopedic
      implants, particularly those with complex shapes.

PMID- 27717914
TI  - Reversibly pH-responsive polyurethane membranes for on-demand intravaginal drug
      delivery.
AB  - : To provide better protection for women against sexually transmitted infections,
      on-demand intravaginal drug delivery was attempted by synthesizing reversibly pH
      sensitive polyether-polyurethane copolymers using poly(ethylene glycol) (PEG) and
      1,4-bis(2-hydroxyethyl)piperazine (HEP). Chemical structure and thermo
      characteristics of the synthesized polyurethanes were confirmed by attenuated
      total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), 1H-nuclear
      magnetic resonance (1H-NMR), and melting point testing. Membranes were cast by
      solvent evaporation method using the prepared pH-sensitive polyurethanes. The
      impact of varying pH on membrane swelling and surface morphology was evaluated
      via swelling ratio change and scanning electron microscopy (SEM). The prepared pH
      responsive membranes showed two times higher swelling ratio at pH 4 than pH 7 and
      pH-triggered switchable surface morphology change. The anionic anti-inflammatory
      drug diclofenac sodium (NaDF) was used as a model compound for release studies.
      The prepared pH-responsive polyurethane membranes allowed continuous NaDF release
      for 24h and around 20% release of total NaDF within 3h at pH 7 but little-to-no
      drug release at pH 4.5. NaDF permeation across the prepared membranes
      demonstrated a reversible pH-responsiveness. The pH-responsive polyurethane
      membranes did not show any noticeable negative impact on vaginal epithelial cell
      viability or induction of pro-inflammatory cytokine production compared to
      controls. Overall, the non-cytotoxic HEP-based pH-responsive polyurethane
      demonstrated its potential to be used in membrane-based implants such as
      intravaginal rings to achieve on-demand "on-and-off" intravaginal drug delivery.
      STATEMENT OF SIGNIFICANCE: A reversible and sharp switch between "off" and "on"
      drug release is achieved for the first time through new pH-sensitive polyurethane
      membranes, which can serve as window membranes in reservoir-type intravaginal
      rings for on-demand drug delivery to prevent sexually transmitted infections
      (STIs). Close to zero drug release occurs at the normal vaginal pH (4.5) for
      minimal side effects. Drug release is only triggered by elevation of pH to 7
      during heterosexual intercourse. The reversibly sharp and fast "on-and-off"
      switch arises from the creative incorporation of a pH-sensitive monomer in the
      soft segment of polyurethane. This polyurethane biomaterial holds great potential
      to better protect women who are generally at higher risk and are more vulnerable
      to STIs.

PMID- 27717916
TI  - Fabrication of novel ultradeformable bilosomes for enhanced ocular delivery of
      terconazole: In vitro characterization, ex vivo permeation and in vivo safety
      assessment.
AB  - The objective of this work was to encapsulate terconazole (TCZ), a water
      insoluble antifungal drug, into novel ultradeformable bilosomes (UBs) for
      achieving enhanced ocular delivery. In addition to the constituents of the
      conventional bilosomes; namely, Span 60, cholesterol, and the bile salts, UBs
      contain an edge activator which imparts extra elasticity to the vesicles and
      consequently hypothesized to result in improved corneal permeation. In this
      study, TCZ loaded UBs were prepared utilizing ethanol injection method according
      to 23 full factorial design. The investigation of the influence of different
      formulation variables on UBs properties and selection of the optimum formulation
      was done using Design-Expert(r) software. The selected UBs formulation (UB1;
      containing 10mg bile salt and 5mg Cremophor EL as an edge activator) showed
      nanosized spherical vesicles (273.15+/-2.90nm) and high entrapment efficiency
      percent (95.47+/-2.57%). Results also revealed that the optimum UBs formulation
      exhibited superior ex vivo drug flux through rabbit cornea when compared with
      conventional bilosomes, niosomes, and drug suspension. Furthermore, in vivo
      ocular tolerance and histopathological studies conducted using male albino
      rabbits proved the safety of the fabricated UBs after topical ocular application.
      Overall, the obtained results confirmed that UBs could be promising for ocular
      drug delivery.

PMID- 27717915
TI  - Changes in apoptosis-related gene expression and cytokine release in breast
      cancer cells treated with CpG-loaded magnetic PAMAM nanoparticles.
AB  - CpG-oligodeoxynucleotide (CpG-ODN) can function as an immune adjuvant.
      Previously, we showed that stimulation of breast cancer cells with CpG-ODN
      conjugated with PAMAM dendrimer-coated magnetic nanoparticles (DcMNPs) has
      induced apoptosis. The aim of the current study was to evaluate the expression
      levels of some apoptosis-regulating genes in several human breast cancer cells
      treated with CpG/DcMNPs. Treated MDA-MB231 cells showed an increase in Noxa and
      Bax gene expression levels, whereas the expression level of Survivin decreased.
      Similarly, Noxa gene was overexpressed in treated MCF7 cells. In treated SKBR3
      cells, a decline in the c-Flip mRNA level was determined. Furthermore, release of
      cytokines, IL-6, IL-10, and TNF-alpha, was determined in cell culture
      supernatants. CpG/DcMNP treatment leads to an increase in the release of IL-6 in
      MDA-MB231 and SKBR3 cells, whereas release of IL-10 and TNF-alpha did not change
      significantly. It is indicated that CpG-ODN may show its cytotoxic effect by
      regulating the expression of apoptosis-related genes and the release of cytokine
      in breast cancer cells.

PMID- 27717917
TI  - Comparison of breaking tests for the characterization of the interfacial strength
      of bilayer tablets.
AB  - The bilayer tableting technology is gaining more acceptance in the drug industry,
      due to its ability to improve the drug delivery strategies. It is currently
      assessed by the European Pharmacopoeia, that the mechanical strength of tablets
      can be evaluated using a diametral breaking tester. This device applies a force
      diametrically, and records the tablet breaking point. This approach has been used
      to measure the structural integrity of single layer tablets as well as bilayer
      (and multi-layer) tablets. The latter ones, however, have a much complex
      structure. Therefore, testing a bilayer tablet with the currently used breaking
      test methodology might not be appropriate. The aim of this work was to compare
      results from several tests that have been proposed to quantify the interfacial
      strength of bilayer tablets. The obtained results would provide an indication on
      which tests are appropriate to evaluate the robustness of a bilayer tablet.
      Bilayer tablets were fabricated using a model formulation: Microcrystalline
      Cellulose (MCC) for the first layer, and spray dried lactose (SDLac) as second
      layer. Each set of tablets were tested using the following tests: Diametral Test,
      Shear Test and Indentation Test. The tablets were examined before and after the
      breaking test using Scanning Electron Microscopy (SEM). When a bilayer tablet was
      subjected to shearing or indentation, it showed signs of clear delamination.
      Differently, using the diametral test system, the tablets showed no clear
      difference, before and after the testing. However, when examining each layer via
      SEM, it was clear that a fracture occurred in the layer made of SDLac. Thus, the
      diametral test is a measure of the strength of one of the two layers and
      therefore it is not suited to test the mechanical strength of bilayer tablets.

PMID- 27717918
TI  - Evaluation of mesoporous carbon aerogels as carriers of the non-steroidal anti
      inflammatory drug ibuprofen.
AB  - Towards the development of novel drug carriers for oral delivery of poorly
      soluble drugs mesoporous aerogel carbons (CAs), namely CA10 and CA20 with
      different pore sizes (10 and 20nm, respectively), were evaluated. The non
      steroidal anti-inflammatory lipophilic compound ibuprofen was incorporated via
      passive loading. The drug loaded carbon aerogels were systemically investigated
      by means of High-Resolution Transmission Electron Microscopy (HR-TEM), Nitrogen
      physisorption studies, X-ray diffraction (XRD), Differential Scanning Calorimetry
      (DSC), X-ray photon electron spectroscopy (XPS) and zeta-potential studies. In
      vitro release studies were performed in simulated intestinal fluids reflecting
      both fasted (FaSSIF) and fed (FeSSIF) state conditions. Cytotoxicity studies were
      conducted with human intestinal cells (Caco-2). Drug was in an amorphous state in
      the pores of the carbon carrier as shown from the physicochemical
      characterization studies. The results showed marked differences in the release
      profiles for ibuprofen from the two aerogels in the media tested whereas in vitro
      toxicity profiles appear to be compatible with potential therapeutic applications
      at low concentrations.

PMID- 27717919
TI  - iTAK: A Program for Genome-wide Prediction and Classification of Plant
      Transcription Factors, Transcriptional Regulators, and Protein Kinases.

PMID- 27717921
TI  - Evaluation of a Digital Game-Based Learning Program for Enhancing Youth Mental
      Health: A Structural Equation Modeling of the Program Effectiveness.
AB  - BACKGROUND: Digital game-based learning (DGBL) makes use of the entertaining
      power of digital games for educational purposes. Effectiveness assessment of DGBL
      programs has been underexplored and no attempt has been made to simultaneously
      model both important components of DGBL: learning attainment (ie, educational
      purposes of DGBL) and engagement of users (ie, entertaining power of DGBL) in
      evaluating program effectiveness. OBJECTIVE: This study aimed to describe and
      evaluate an Internet-based DGBL program, Professor Gooley and the Flame of Mind,
      which promotes mental health to adolescents in a positive youth development
      approach. In particular, we investigated whether user engagement in the DGBL
      program could enhance their attainment on each of the learning constructs per
      DGBL module and subsequently enhance their mental health as measured by
      psychological well-being. METHODS: Users were assessed on their attainment on
      each learning construct, psychological well-being, and engagement in each of the
      modules. One structural equation model was constructed for each DGBL module to
      model the effect of users' engagement and attainment on the learning construct on
      their psychological well-being. RESULTS: Of the 498 secondary school students
      that registered and participated from the first module of the DGBL program, 192
      completed all 8 modules of the program. Results from structural equation modeling
      suggested that a higher extent of engagement in the program activities
      facilitated users' attainment on the learning constructs on most of the modules
      and in turn enhanced their psychological well-being after controlling for users'
      initial psychological well-being and initial attainment on the constructs.
      CONCLUSIONS: This study provided evidence that Internet intervention for mental
      health, implemented with the technologies and digital innovations of DGBL, could
      enhance youth mental health. Structural equation modeling is a promising approach
      in evaluating the effectiveness of DGBL programs.

PMID- 27717920
TI  - The Effectiveness of Lower-Limb Wearable Technology for Improving Activity and
      Participation in Adult Stroke Survivors: A Systematic Review.
AB  - BACKGROUND: With advances in technology, the adoption of wearable devices has
      become a viable adjunct in poststroke rehabilitation. Regaining ambulation is a
      top priority for an increasing number of stroke survivors. However, despite an
      increase in research exploring these devices for lower limb rehabilitation,
      little is known of the effectiveness. OBJECTIVE: This review aims to assess the
      effectiveness of lower limb wearable technology for improving activity and
      participation in adult stroke survivors. METHODS: Randomized controlled trials
      (RCTs) of lower limb wearable technology for poststroke rehabilitation were
      included. Primary outcome measures were validated measures of activity and
      participation as defined by the International Classification of Functioning,
      Disability and Health. Databases searched were MEDLINE, Web of Science (Core
      collection), CINAHL, and the Cochrane Library. The Cochrane Risk of Bias Tool was
      used to assess the methodological quality of the RCTs. RESULTS: In the review, we
      included 11 RCTs with collectively 550 participants at baseline and 474
      participants at final follow-up including control groups and participants post
      stroke. Participants' stroke type and severity varied. Only one study found
      significant between-group differences for systems functioning and activity.
      Across the included RCTs, the lowest number of participants was 12 and the
      highest was 151 with a mean of 49 participants. The lowest number of participants
      to drop out of an RCT was zero in two of the studies and 19 in one study.
      Significant between-group differences were found across three of the 11 included
      trials. Out of the activity and participation measures alone, P values ranged
      from P=.87 to P <=.001. CONCLUSIONS: This review has highlighted a number of
      reasons for insignificant findings in this area including low sample sizes,
      appropriateness of the RCT methodology for complex interventions, a lack of
      appropriate analysis of outcome data, and participant stroke severity.

PMID- 27717922
TI  - Interictal heart rate in patients with epilepsy.
AB  - INTRODUCTION: Electrocardiographic abnormalities in patients with epilepsy are
      related to the presence of discharges in central autonomic structures and the
      effect of antiepileptic drugs. These patients are at risk for sudden unexpected
      death, and cardiac arrhythmias are one of the most probable causes related to it.
      THE AIM: The heart rate (HR) assessment recorded on electrocardiography (ECG) in
      the interictal period in patients with newly diagnosed and previously treated
      epilepsy, depending on the type of changes in electroencephalography (EEG) and
      the treatment option. MATERIAL AND METHODS: Fifty patients with epilepsy were
      enrolled in the study: 22 comprised a non-treated patient (NTP) group with newly
      diagnosed epilepsy and 28 comprised a treated patient (TP) group that had been
      treated for more than 2 years. Resting ECG and EEG were performed in all
      patients. RESULTS: A significantly higher HR was recorded in the TP group
      compared to the NTP group (80+/-13 vs 67+/-15 bpm, p=0.00006). The tendency to
      higher HR was observed in polytherapy patients, carbamazepine patients and in
      patients with a focus in the right hemisphere. CONCLUSIONS: There is a
      relationship between the presence of the disorders related to bioelectric
      activities of the brain and the heart, therefore the ECG should be periodically
      monitored in epileptic patients.

PMID- 27717923
TI  - [Health behavior of polish physicians].
AB  - INTRODUCTION: Physicians are perceived by patients as a competent source of
      information about health. However, the professional knowledge of health does not
      have to be identical with practicing health behavior in private life. THE AIM: To
      assess the health behaviors of Polish doctors. MATERIAL AND METHODS: We examined
      614 medical practitioners. The mean age was 49.16+/-13.56 years. The average body
      mass index (BMI) was 24.81+/-4.09 kg /m2. The subjects completed medical studies
      on average 23.68+/-13.77 years ago. The majority (80.88%) had at least one
      medical specialization. The method was a diagnostic survey. Health Behavior
      Inventory (Inwentarz Zachowan Zdrowotnych or IZZ) was used and a special
      questionnaire containing questions about health behaviors not included in the
      IZZ. RESULTS: The dominance of unhealthy behaviors was observed in 27.34% of the
      group studied, the dominance of healthy behavior in 29.45% of participants. The
      others (43.21%) declared a similar extent of behavior in both categories.
      Participants were working an average of 40.42+/-18.77 hours a week, while they
      were sleeping an average of 6.56 +/- 1.03 hours a day. We observed the difference
      in the results of IZZ according to gender (p <0.01) and the partnership situation
      (p <0.01). It was also shown that there is a positive correlation between the
      result of IZZ and the time elapsed since the completion of specialization (p
      <0.01). Univariate analysis demonstrated a positive correlation between the fact
      of having a partner and a result of IZZ (p <0.01) and the difference between
      people showing healthy and unhealthy behaviors in terms of age (p<0.05) and the
      time elapsed since the completion of specialization (p<0.01). CONCLUSIONS: 1.
      Polish doctors are a diverse group in terms of health behavior. 2. Undertaking
      health behaviors by doctors is encouraged by: female sex, older age, lower BMI, a
      long time after completion of specialization. 3. Performing the medical
      profession is not the same as the manifestation of healthy behavior in private
      life.

PMID- 27717924
TI  - [Mechanisms of nitroxide-ergic dysregulation in tissues of parodontium in rats
      under combined excessive sodium nitrate and fluoride intake].
AB  - INTRODUCTION: intake of inorganic nitrates is typically accompanied by production
      of excessive amount of nitric oxide (NO), which level is maintained by the
      mechanism of autoregulation known as the NO cycle. Hypothetically, this process
      may be disrupted with fluorides that are able to suppress arginase pathway of L
      arginine metabolism, which competes with NO-synthase pathway. AIM: to study
      mechanisms of disregulation of oxidative (NO-synthase) and non-oxidative
      (arginase) metabolic pathways of L-arginine in the tissues of periodontium under
      combined excessive sodium nitrate and fluoride intake. MATERIAL AND METHODS:
      these investigations were carried out on 90 white Wistar rats. Homogenates of
      parodontium soft tissues were used to assess spectrophotometrically the total
      activities of NO-synthase (NOS), arginase, ornithine decarboxylase as well as the
      peroxynitrite concentration. RESULTS: typical for the isolated sodium nitrate
      administration inhibition of total NOS activity varies under combined
      administration of nitrate and sodium fluoride and is usually manifested by its
      hyperactivation that is accompanied by an increase in peroxynitrite
      concentration. At this time arginase and ornithine decarboxylase activity is
      observed to be substantially reduced. The administration of aminoguanidine, an
      iNOS inhibitor, (20 mg/kg, twice a week during the experiment) increases arginase
      and ornithine decarboxylase activities, and the administration of L-arginine (500
      mg/kg, twice a week) results in the increase of arginase activity. The
      administration of L-selenomethionine, a peroxynitrite scavenger (3 mg/kg, twice a
      week), and JSH-23 (4-methyl-N-(3-phenylpropyl) benzene-1,2-diamine, an inhibitor
      of NF-kappaB activation (1 mg/kg, twice a week) for modeling binary nitrate and
      fluoride intoxication reduces the total concentration of NOS activity and
      peroxynitrite concentration, and increases ornithine decarboxylase activity.
      CONCLUSIONS: the combined effect of nitrate and sodium fluoride for 30 days leads
      to disregulatory increased activity of NO-synthase enzymes and reduction of
      arginase pathway of L-arginine in the soft tissues of parodontium that is
      promoted by hyperactivation of iNOS and NF-kappaB, and increased peroxynitrite
      production.

PMID- 27717925
TI  - Electromyographic characteristic of orbicularis oris in patients with dental
      crowding in permanent occlusion.
AB  - INTRODUCTION: electromyographic indices were developed for complex analysis of
      functional condition of orbicularis oris. AIM: to study electromyographic indices
      of orbicularis oris in patients with dental crowding in permanent occlusion.
      MATERIALS AND METHODS: thirty four patients with malocclusion and a severe degree
      of severity of dental crowding (15 males, 19 females, aged 16-29 years) who
      underwent orthodontic examination. The treatment group was divided into three:
      Group Ia comprised 11 subjects with mandibular crowding (mean age 19,27 +/- 1,08
      years); group Ib, 10 patients with maxillary dental crowding (mean age 20,10 +/-
      1,60 years) and group Ic, 13 subjects with both maxillary and mandibular crowding
      (mean age 20,15 +/- 1,45 years). The control group consisted of 10 patients with
      malocclusions but without dental crowding (mean age 20,70 +/- 1,32 years). The
      findings were compared with similar indices in subjects with normal occlusion
      (mean age 21,3 +/- 1,25 years). The index of orbicularis oris activity (ACTIV,%)
      was determined for each patient. A Student's t-test was used to analyze
      statistical difference between different groups. RESULTS: patients having
      crowding of maxillary teeth showed greater activity of muscles of the upper lip
      during maximum voluntary clenching (ACTIV= -0,99+/-7,44%). Activity of the
      muscles of the lower lip in patients with crowding of mandibular teeth
      (ASTIV=20,52+/-4,22%) and crowding of maxillary and mandibular teeth
      (ASTIV=17,93+/-4,33%) is prevailing. CONCLUSIONS: activity of the orbicularis
      oris in patients with malocclusion, complicated by dental crowding depend on
      clinical localization of crowding.

PMID- 27717926
TI  - [Ukrainian experience of health care for patients with diabetes].
AB  - INTRODUCTION: diabetes mellitus is among the main challenges in the establishment
      of an effective health care system. A significant prevalence of disease and,
      consequently, a large number of complications, caused by it, provokes a constant
      searching for new measures and means for the struggle. In Ukraine, as in other
      countries, among methods of such a struggle is to standardize medical care. AIM:
      explore the state of health care for patients with diabetes in Ukraine. MATERIALS
      AND METHODS: to study the frequency of the measurement of certain quality
      indicators of patients with diabetes it was organized cross-sectional trial by
      the anonymous survey of 242 patients with a previously verified diagnosis of more
      than 2 years, at services of primary and secondary health care. RESULTS: obtained
      results are showed the presence of significant weaknesses in the providing of
      quality health care for patients with diabetes, in comparison with the
      requirements of national standards. Considering the features of detected flaws,
      they should be regarded as a result of an insufficient level of knowledge of
      their disease among patients and, possibly, the low average level of their
      income. CONCLUSIONS: the level of health care for patients of both types of
      diabetes does not meet recommended. Recommendations, which does not require
      personal expenses, are realized more efficiently, but not at the target level.
      Among the Ukrainian population level of implementation of the recommendations
      related to personal costs spending is at a critically low level, regardless of
      the type of disease. Solving of the identified problems could be achieved through
      the development of the network of primary health care services, closer to the
      patients, in conjunction with the organization and promotion of self-educational
      projects for patients and their physicians.

PMID- 27717927
TI  - Characteristics of the anthropometric measures and biological age of girls of
      Yakut ethnicity depending on tanner's index.
AB  - INTRODUCTION: severe climatic conditions of Yakutia influence the human
      morphofunctional status and it requires a comprehensive biomedical researches.
      The aim of this study was to examine the characteristics of the anthropometric
      measures and biological age of Yakut girls aged 16-20 depending on Tanner's
      index. MATERIALS AND METHODS: the analysis of anthropometric examination of 1276
      girls is presented. Anthropometric measurements were performed using the method
      of V.V. Bunak (1941). The absolute values of the main components of the body were
      estimated according to Matiegka's formula (1921). The body mass index (BMI) was
      used. The type of body build was determined by Tanner's index (1968). Biological
      age was estimated by the coefficient of aging rate (A.G. Gorelkin, B.B.
      Pinkhasov, 2010). Obtained material was processed by the method of variation
      statistics with the use of SPSS (version 17.0). We used the methods of parametric
      and nonparametric statistics. RESULTS: the constitutional characteristics of
      girls have revealed the predominance of mesomorphic body type. Values of fat and
      bone body components had no significant difference depending on the body type by
      Tanner. Significant differences between the parameters of the pelvis and the
      amount of muscle body component were detected in the girls of gynemorphic and
      andromorphic body types. CONCLUSIONS: we revealed ethno-territorial differences
      among girls, which are characterized by the predominance in Yakut girls of the
      mesomorphic type of constitution by Tanner's index. The study of the indicators
      of biological age has elucidated constitutional differences.

PMID- 27717928
TI  - Resveratrol more effectively than quercetin reduces endothelium degeneration and
      level of necrosis factor alpha in patients with coronary artery disease.
AB  - INTRODUCTION: endothelial dysfunction (ED) is one of the most important links in
      the pathogenesis of atherosclerosis (ASVD) - morphological basis of coronary
      artery disease (CAD). OBJECTIVE: to study the effect of polyphenolic
      antioxidants, resveratrol and quercetin, on endothelial degeneration factors in
      CAD patients. MATERIALS AND METHODS: the study involved 93 patients with coronary
      artery disease: stable angina pectoris, FC II. The cytofluorometric technique was
      applied to define the level of circulating endothelial microparticles (EMP)
      CD32+CD40+ in peripheral blood in order to identify ED. The content of tumor
      necrosis factor alpha (TNF-alpha), fibrinogen, hemocoagulation and lipid profile
      parameters were being determined in the blood, as well. Patients were divided
      into 3 groups. Basic therapy (beta-blockers, statins, aspirin) was prescribed to
      33 persons of the comparison group, patients of the study group 1 (30 persons)
      additionally received resveratrol at a dose of 100 mg daily, patients of the
      study group 2 (30 persons) got quercetin at a dose of 3 g per day. In 2 months,
      the second examination of the patients was performed in the amount indicated.
      RESULTS: under the influence of resveratrol a significant reduction of the level
      of TNF-alpha and the number of EMP in peripheral blood was shown, in contrast to
      the results of other study groups. All groups showed a decrease in total
      cholesterol and low-density lipoprotein cholesterol, statistical differences
      between data of groups were not found. Indicators of coagulogramma in all study
      groups did not change significantly, however, there was a statistically
      significant reduction of fibrinogen in the blood. CONCLUSIONS: resveratrol,
      unlike quercetin, has a positive effect on the endothelial function and systemic
      inflammation, which may be the result of its influence on intracellular molecular
      cascades associated with the nuclear transcription factor of NF-kB.

PMID- 27717929
TI  - Ultrasonographic peculiarities of fetoplacental complex in pregnancy complicated
      by intrauterine infection.
AB  - INTRODUCTION: the relevance of intrauterine infections is determined by
      significant peri- and postnatal loss as well as health impairment, which often
      results in disability and reduced quality of life. Ultrasonography is employed in
      order to provide a reliable assessment of the functional state of the
      fetoplacental system secondary to intrauterine fetal infection in the course of
      pregnancy. Ultrasound imaging is essential in diagnosis of various preclinical
      complications of pregnancy and detection of abnormalities in the developing
      fetus. The aim of the study was to perform ultrasonographic assessment of
      fetoplacental complex in pregnancy complicated by intrauterine infection.
      MATERIALS AND METHODS: the study involved 304 pregnant women who underwent
      ultrasonographic and bacteriological somatogenic examination. The women were
      divided into the following groups depending on the presence and nature of the
      diagnosed infection: Group 1 - 50 patients with normal pregnancy, who were not
      found to have signs of infection (control group), Group 2 - 50 pregnant women
      with viral infections (CMV and herpes simplex virus); Group 3 - 50 pregnant women
      with bacterial infections (chlamydia, ureaplasma, mycoplasma), Group 4 - 154
      patients with mixed viral and bacterial infections. Clinical groups with
      intrauterine infections (IUI) were considered main ones. RESULTS: increased
      echogenicity of the endothelium of internal and provisional organs was considered
      to be the main ultrasonographic sign of intrauterine fetal infections as these
      changes were equally observed in pregnant women of the main group. Main symptoms
      of viral infections included ventriculomegaly, hypoplasia of the chest, echogenic
      fibrous inclusions in the papillary muscles and valve flaps, hepatomegaly,
      placental hypoplasia, oligohydramnios. Dolichocephalic skull, choroid plexus
      cysts, gastromegaly, placental calcifications, polyhydramnios were more common in
      bacterial infections. Pregnant women with mixed viral and bacterial infections
      were found to have those and other signs of infection in equal measure.
      CONCLUSION: ultrasonographic somatogenic examination is of great diagnostic
      importance in preclinical diagnosis of intrauterine infection. Timely detection
      of changes in fetus and provisional organs provides a differentiated approach to
      administration of pathogenetically targeted treatment of this group of patients.

PMID- 27717930
TI  - [Analysis of the fatty acid profile of vegetarian and non-vegetarian diet in the
      context of some diet-related diseases prevention].
AB  - INTRODUCTION: Research increasingly provide evidence that vegetarian diet can
      have a positive impact on health. The aim of this study was to analyze the fatty
      acid profile of vegetarian and non-vegetarian diet and prove which of them is
      more optimal in the context of some diet-related diseases prevention. MATERIAL
      AND METHODS: The study involved 83 women (47 vegetarians and 36 non-vegetarians).
      Estimates of the supply of individual fatty acids in the diet was based on
      analysis of 3-day dietary records (calculations in a computer program DIETA 5).
      RESULTS: Found: - in vegan diet significantly lower percentage of energy from SFA
      than in lactoovovegetarian diet and non-vegetarian diet (5,2% vs 11,2% i 11,9%), 
      in vegan and lactoovovegetarian diet - significantly higher percentage of energy
      from PUFA than in non-vegetarian diet (9,2% i 7,8% vs 5,0%), - in vegan and
      lactoovovegetarian diet - significantly higher percentage of energy from LA than
      in non-vegetarian diet (6,7% i 5,5% vs 3,9%), - in vegan and lactoovovegetarian
      diet - significantly higher percentage of energy from ALA than in non-vegetarian
      diet (1,3% i 1,2% vs. 0,8%) - in vegan and lactoovovegetarian diet -
      significantly lower intake of EPA+DHA than in non-vegetarian diet (0 mg i 15 mg
      vs 76 mg), - only 25% of non-vegetarian diets fulfilled recommendations on the
      content of EPA + DHA Conclusions: Vegetarian, particularly vegan, nutrition may
      promote good balancing of the fatty acids in the diet, except for the long chain
      polyunsaturated omega-3, which are also deficient in the case of conventional
      diet.

PMID- 27717931
TI  - Problems and challenges in the early period of rehabilitating patients with
      severe hypothermia treated using ecmo support.
AB  - : The objectives: To show and discuss the most frequent functional problems
      encountered in patients who underwent extracorporeal membrane oxygenation (ECMO)
      treatment after severe hypothermia and point out appropriate physiotherapy
      procedures used in order to diminish the effects of hypothermia on the human
      organism. It is necessary to look for effective physiotherapeutic solutions,
      especially that the number of scientific publications on the subject is very
      limited. DESIGN: Retrospective analysis Setting: Severe Accidental Hypothermia
      Center ( medical intensive care unit of a university hospital) Patients or
      participants: Nineteen patients who were qualified for ECMO in Severe Accidental
      Hypothermia Center Intervention: At least three times a day rehabilitation
      session (physiotherapeutic procedures adequate to patient problems) and
      interventions in case of emergency. Physiotherapy staff in the Center has regular
      work hours and night duties, so can provide round-the clock rehabilitation
      treatment adjusted to the dynamically changing clinical picture of the patient.
      METHODS AND RESULTS: We analyzed the group of patients who were treated in our
      center from July 2013 to March 2015. The degree of functional complications
      increased with the duration and extent of hypothermia and time of conducting
      extracorporeal therapy. The frequent problems were: respiratory failure due to
      sputum retention (25%) or sternum fracture due to resuscitation (25%), lower and
      upper extremity muscle weakening (75%), peroneal nerve palsy (25%). In the first
      period of hospitalization all of patients have generalised edema. As a result of
      the treatment and rehabilitation, full stabilization of the cardiovascular -
      respiratory system and full recovery of neurological functions was achieved in 14
      persons (73.68%). CONCLUSION: early and round-the clock physiotherapy treatment
      adequate to appearing patient's syndromes seems crucial for his physical and
      mental recovery after severe accidental hypothermia treated by ECMO support. In
      order to attain therapeutic success, it is indispensable to work in experienced,
      multidisciplinary team.

PMID- 27717932
TI  - [Variable magnetic fields in the treatment of tics disorders - preliminary
      results].
AB  - INTRODUCTION: Tics disorders is frequent pathological syndrome, particularly
      typical for children's age. The symptoms of this disease are differential, and
      their intensification individualized, which makes difficult unique recognition.
      Tics disorders concern the most often the muscles of face, head, upper limbs and
      trunk. MATERIAL AND METHODS: The study group consisted of 16 patients (11 boys
      and 5 girls) with tics complex disorders about unknown etiology particularly
      relating of face and upper limbs muscles. In the treatment were the interventions
      with use a magnetotherapy and magnetostimulation applied. The procedures were
      ones daily by 3 weeks in two series executed. It author's pool was the frequency
      of occurrence tics disorders as well as the proportional opinion of effectiveness
      conducted treatment estimated. RESULTS: After 10 weeks in 14 patients was the
      decrease of occurrence frequency involuntary movements observed, in proportional
      scale about 75%. The results of subjective opinion of mood showed, that decrease
      the frequency tics disorders had in all children the direct shift on improvement
      their mood, and also satisfaction in their parents. CONCLUSIONS: The use of
      variable magnetic fields influenced on decrease the occurrence frequency tics
      disorders, and also on improvement quality of life the treated patients.

PMID- 27717933
TI  - Antiviral activity of the "Virus Blocking Factor" (VBF) derived i.a. from
      Pelargonium extract and Sambucus juice against different human-pathogenic cold
      viruses in vitro.
AB  - THE AIM: The in-vitro antiviral activity of the "Virus Blocking Factor" (VBF), a
      combination of Pelargonium extract and Sambucus juice with addition of Betaglucan
      1,3 / 1,6, Zincum gluconium, Acidum ascorbicum, was studied against human
      pathogenic viruses: Influenza A H1N1 (FluA H1N1), Rhinovirus B subtype 14
      (HRV14), Respiratory Syncytial Virus (RSV), Parainfluenzavirus subtype 3 (Para
      3), and Adenovirus C subtype 5 (Adeno 5). METHOD: Antiviral activity was assessed
      using plaque-reduction assays after adding the test substance post infection of
      the MDCK, HeLa and HEp-2 cells with the viruses. Ribavirin Virazol and - in case
      of Adenovirus an internal laboratory standard - were used as positive controls.
      Cytotoxic effects of VBF and VBF Control onto the virus permissive MDCK, HeLa and
      HEp-2 cells were examined. Non-toxic concentrations of VBF were determined by the
      Methylthiazoletetrazolium test (MTT-Test). RESULTS AND CONCLUSIONS: In all
      antiviral studies VBF showed (2.1%) a dose-dependent antiviral activity against
      FluA H1N1 and HRV14 at non-toxic concentrations. A very strong effect was
      demonstrated in concentrations of 2.5% and 1.25% where replication of H1N1 and
      HRV14 was nearly completely blocked. Dose-dependent antiviral activity was
      detectable against RSV in a concentration range of 1.25% to 0.63% of the test
      item. Due to toxic side effects of a 2.5% concentration at least a "minor effect"
      of about 30% (1.25% solution) against Para 3 infected HEp-2 cells could be
      determined. Concerning Adeno 5 not any antiviral activity could be demonstrated
      in all studies with all tested substance concentrations of VBF. VBF Control did
      not show any cytotoxicity and antiviral effects. Further research is needed to
      elucidate clinical effect of VBF.

PMID- 27717934
TI  - [Definitions destruction of endothelial cells as a marker of endothelial
      dysfunction in aging men].
AB  - INTRODUCTION: Ukraine occupies the 143 place in the world in life expectancy and
      the first place in terms of mortality. The main cause of death - cardiovascular
      diseases - 58%. Recent studies show the important and independent role of
      endothelium in the development of cardiovascular disease. THE AIM: examination of
      the endothelium destruction in aging men by determining the level of surface
      specific antigens of endothelial microparticles. MATERIALS AND METHODS: 88 men
      age from 45 to 76 years. 50 people of the main group had a history of the second
      type diabetes mellitus (DM-2) combined with arterial hypertension (AH). The
      control group included 38 men without aforementioned diseases. Also, men were
      divided into two groups by age: 45-59 years and over 60. RESULTS: in the main
      subgroup I endothelin level was higher than the control subgroup I: 2,07 +/- 0,6
      and 1,27 +/- 0,25 (p <0.05). In main subgroup II endothelin level was also
      significantly higher compared with the specified index in control subgroup II:
      3,91 +/- 0,7 and 1,79 +/- 0,27 (p <0.05). Among patients of the main subgroup II
      endothelin level (3,88 +/- 0,7 and 2,04 +/- 0,6 (p <0.05)), and triglycerides
      (2,77 +/- 0,08 vs. 1.99 +/- 0.05 (p <0.05)) was higher compared with the I
      subgroup. CONCLUSIONS: age androgen deficiency is accompanied by lipid
      metabolism, development of endothelial dysfunction, insulin resistance, diabetes
      and hypertension. Reduction of the cardiovascular risk includes measures aimed at
      normalizing hormonal balance and lipid metabolism in aging men with DM-2 and
      hypertension.

PMID- 27717935
TI  - Clinical examples of left ventricular non-compaction in adults.
AB  - INTRODUCTION: isolated left ventricular non-compaction (LVNC) is a heart disease
      with rather distinct morphologic and clinical manifestations. Available in the
      literature information about LVNC considering multiple left ventricle abnormal
      chords (LVAC) as one of its criterion motivated us to review the results obtained
      in the study of young patients with this pathology. The aim of the research was
      to demonstrate different clinical variants of left ventricular non-compaction
      course in adult patients and to clarify some pathogenetic aspects of this
      pathology. Materials and metods: comprehensive examination of 28 patients with
      multiple LVAC, 12 patients with LVNC and dilated idiopathic cardiomyopathy aged
      16-36 was performed. RESULTS: according to the results of our research, 16 of 28
      patients with multiple LVAC of left ventricle had ejection fraction more than
      55%, in 6 patients this index range was 50-54%, in 6 it was 45-49%. Multiple LVAC
      were found to be associated with significantly greater clinical, phenotypic,
      structural and hemodynamic changes when compared both to control and solitary
      LVAC of any location (r<0.05). There were 12 young patients with multiple LVAC
      and ejection faction 22-41%. The detailed analysis of echocardiographic data in
      dynamics revealed other criteria of LVNC in all the patients. The data obtained
      suggest the relationship between pathogenetic mechanisms of heart pathology
      development in patients with connective tissue dysplasia syndrome and in patients
      with LVNS. Echocardiographic evidences of multiple LVAC designate the necessity
      of targeted search of left ventricular non-compacted signs and timely detection
      of left ventricular dilation.

PMID- 27717936
TI  - [Alteration mechanisms of oxidative stress at periodontal tissues of rats in a
      simulated periodontitis and elaborate methods of their correction].
AB  - INTRODUCTION: one of the peroxidation stress mechanisms is inducible NO synthase
      (iNOS) expression involved in the pathogenesis of periodontitis. AIM: to access
      the influence of isoform NO synthase (NOS) on alteration mechanisms of oxidative
      stress at periodontal tissues of 50 mature rats in a simulated periodontitis
      (SP). MATERIALS AND METHODS: a SP at rats was induced by a high-carbohydrate,
      high-fat (HCHF) diet. Treated SP rat groups were intragastrically administered
      with selective neuronal NOS (nNOS) inhibitor 7-nitroindazole, selective inducible
      NOS (iNOS) inhibitor aminoguanidine, and nitric oxide synthase substrate L
      arginine. Oxidative stress level in the homogenated soft periodontal tissues was
      evaluated by TBARS (thiobarbituric acid reactive substances) level before and
      after 1,5 hours of incubation. Antioxidant response was evaluated by the increase
      in concentration of TBARS for incubation, and by antioxidant enzyme activity -
      superoxide dismutase and catalase. RESULTS: nNOS activity increase in a SP
      considerably limits oxidative stress activation at periodontal tissues, decreases
      antioxidant response, but heightens catalase activity. iNOS functional activity
      stimulates oxidative stress at periodontal tissues of rats, decreases antioxidant
      response. L-arginine in a MS effectively repaired antioxidant response at
      periodontal tissues that probably will give positive result at complex treatment
      of periodontitis and MS generally. CONCLUSIONS: in the near future, the
      appropriate regulation of NO activity by using NOS-active agents may provide a
      novel strategy for the periodontal disease prevention and correction in a MS.

PMID- 27717937
TI  - Peculiarities of heart rate in the patients with unstable angina and non-ST
      elevation myocardial infarction and concomitant diabetes mellitus type 2.
AB  - INTRODUCTION: type 2 diabetes mellitus is one of the most important medical and
      social problems in the world. Patients with diabetes are prone to coronary artery
      disease, in particular acute coronary syndrome, with atypical clinical signs and
      susceptibility to tachycardia. Elevated heart rate is an important factor of
      premature mortality in all patients with acute coronary syndrome. The aim of the
      investigation was to reveal the heart rate peculiarities in unstable angina and
      non-ST elevation myocardial infarction patients suffering from diabetes mellitus
      type 2 for more effective treatment of these patients. MATERIALS AND METHODS: 40
      patients with unstable angina and non-ST elevation myocardial infarction were
      examined in the consecutive way during 2013- 2015 years. The patients were
      divided in two groups. The main group consisted of 25 patients with UA and NSTEMI
      with concomitant DM. The control group consisted of 15 patients with UA and
      NSTEMI but without DM. Basic clinical examinations, electrocardiography and 24
      hours electrocardiography monitoring were performed. Carvedilol in the dose from
      12.5 to 25 mg daily was also prescribed. RESULTS: we revealed statistically
      higher heart rate in the patients with unstable angina, non-ST elevation
      myocardial infarction and concomitant DM on hospitalization, at the fifth day of
      treatment and before their discharge from the hospital. CONCLUSIONS: 1. Patients
      with unstable angina and non-ST elevation myocardial infarction in associations
      with diabetes mellitus type 2 are characterized with increased heart rate partly
      resistant to beta-blockers, which indicates worse prognosis of cardiovascular
      diseases. 2. Prescription of carvedilol in daily dose 12.5 - 25 mg. is inadequate
      for obtaining HR < 70 bmp. in some patients with acute coronary syndrome and
      diabetes mellitus. 3. According to heart rate resistance to beta-blockers in
      patients with unstable angina and non-ST elevation myocardial infarction and
      concomitant diabetes mellitus patients need individual titration of higher doses
      of carvedilol.

PMID- 27717938
TI  - Experience of using hippotherapy in complex effects on muscle spirals in children
      with spastic forms of cerebral palsy.
AB  - Matters of physical and medical rehabilitation of children with organic lesions
      of the nervous system, in particular, with cerebral palsy, are actual in
      countries around the world. Hippotherapy is neurophysiologically oriented therapy
      using horses. Determine whether a combination of hippotherapy as a method of
      rehabilitation in the aftermath of outpatient comprehensive impact on MS on a
      stationary phase; Study of the effect of hippotherapy as securing and preparation
      method for learning new postures and movements in children with spastic cerebral
      palsy forms; The study of the possible optimization of psychophysical state,
      activation motivations of patients; Determination of the optimal timing of
      hippotherapy sessions, the number of procedures, the study of possible fatigue
      factor children. HT classes were conducted at the Ippotsentra "Wind of Change" in
      the period 2010-2013 the main group of children surveyed (36 people) with spastic
      forms of cerebral palsy. HT procedure took place twice a day - morning and
      evening - 30 minutes during 10-12 days. Thus, the proposed integration of the HT
      program of complex effects on muscle spirals children with spastic cerebral palsy
      forms is physiologically and anthropologically based on 4-5 day training children
      adequately transferred the full amount of lessons learned new postures and
      movements, HT does not cause complications in the somatic and psycho-emotional
      state of the children, HT enables sensorimotor and psychomotor effects, save and
      normalize muscle tone for a longer period (up to three months), compared with
      traditional methods of physiotherapy. HT can serve as a method of learning a new
      "postures and movements", the preparation of the locomotor apparatus to learn
      walking.

PMID- 27717939
TI  - Features of chronic renal disease in children.
AB  - INTRODUCTION: chronic renal disease (CKD) is the inevitable outcome of many
      chronic diseases of the kidneys, which not all survive. The number of patients
      with chronic renal diseases is constantly growing. Aim to study the level
      osteocalcin and calcitonin and parathyroid hormone and immunological features in
      patients with chronic renal diseases. Materials and method The study involved 10
      children with chronic renal failure at the age from 7 to 14 years in the initial
      stage - GFR 60-40 ml/min, creatinine blood increased to 180 MUmol/l, and 20
      healthy patients as a control group. RESULTS: in the studies there was
      significant increase in the level of calcitonin , osteocalcin, parathyroid
      hormone in patients with chronic renal failure. In patients with chronic renal
      disease decreased indices of cellular and humoral immunity. In children with
      chronic renal disease significantly increased CIK and decreased the content of
      IFN-gamma, FNO-alpha in comparison with the group of healthy children.
      CONCLUSION: revealed that at all stages of CKD patients there is a change of
      level calcitonin, osteocalcin and parathyroid hormone. All patients with CKD,
      there was a reduction of humoral and cellular immunity.

PMID- 27717940
TI  - Sociological research on the population awareness regarding ophthalmological care
      in ukraine.
AB  - INTRODUCTION: nowadays, there are about 45 million blind individuals and,
      according to the prognosis, their quantity will reach over 76 million in 2020. In
      such a way, nowadays ophthalmological problems become more widespread, and the
      market of the ophthalmological services is not studied enough to understand all
      the tendencies and processes. AIM: was to study the patients' awareness on eye
      diseases and choice peculiarities of the information sources and medical
      institutions among various population age groups of Lutsk, Rivne and Ternopil
      cities. MATERIALS AND METHODS: the research was conducted as an anonymous
      questionnaire survey of respondents according to a specially designed integrated
      protocol by means of interviewing people at the streets of Lutsk (n=2000), Rivne
      (n=1500) and Ternopil (n=1500) cities. RESULTS: there was conducted a research on
      the population awareness concerning vision problems, analysis of social factors
      and peculiarities of the choice of information sources about eye diseases and
      factors influencing the choice of a medical institution and an ophthalmologist.
      It was determined that younger population prefers private medical institutions in
      almost half of the cases (95% confidence interval (CI) of the private institution
      choice probability: 0,48-0,52), while older population prefers mainly state ones
      (95% CI of the choice probability: 0,71-0,74). CONCLUSION: it was determined
      depending on the age, the range of people having vision problems varied from 22%
      in the "under 30 years" population group up to 76% in the "over 60 years" group,
      although at least 21,5% of the whole population realizing their problems do not
      address an ophthalmologist.

PMID- 27717941
TI  - The HELIO-geophysical storminess health effects in the cardio-vascular system of
      a human in the middle and high latitudes.
AB  - INTRODUCTION: cardiovascular impairment remains one of the most current problems
      of today's life and the definition of the connection between its development and
      the state of heliogeophysical storminess is currently important. The results of
      long-term researches of communication between cardiovascular catastrophes
      (myocardial infarction) and heliogeophysical storminess in the middle and high
      latitudes are shown in this work. AIM: to study the influence of space weather
      parameters on human cardio-vascular system in the high and middle latitudes. To
      define the particular space weather parameters and the mechanisms of their
      influence on human myocardial infarction progressing. MATERIAL AND METHODS: for
      the statistical processing of medical records data we use a spectral-time
      analysis, a correlation method and a method of overlapping of epochs. We have
      studied about 145 thousand medical records of ambulance medical services for the
      period of 1992 -2001. In order to define the reasons influencing the development
      of a myocardial infarction, we have made a comparison of myocardial infarction
      progress cases with Kp-index characterizing the level of geomagnetic storminess.
      RESULTS: the coincidence of geomagnetic storminess maximum with the cases of
      myocardial infarction, as well as the number of heart attacks excess in 1.5 times
      per a year near the maximum heliogeophysical activity (1992) compared to the year
      near the minimum of activity (1998) indicate possible influence of geomagnetic
      storminess on the myocardial infarction development of people living in
      subauroral latitudes. CONCLUSIONS: it was concluded that the appearance of
      heliogeophysical storminess in the myocardial infarction development in the mid
      latitudes is largely due to the presence of Pc1 geomagnetic pulsations, and in
      the high latitudes, especially in maximum years of heliogeophysical storminess,
      it is due to the geomagnetic storminess caused by the parameters of the solar
      wind and the interplanetary magnetic field.

PMID- 27717942
TI  - [Sarcopenia in rheumatoid arthritis].
AB  - The clinical picture of rheumatoid arthritis covers the condition of chronic
      inflammation connected to the increased concentration of inflammatory mediators,
      reduced physical activity, immobilization caused by pain, stiffness and joint
      destruction as well as accompanying hormonal and metabolic disorders. It all may
      lead to extra-articular complications, also to the loss of muscle mass with the
      weakness of muscle strength, adding to the disability and significantly lowering
      the patients' quality of life. Sarcopenia is an advanced form of muscle mass loss
      which constitutes an independent and vital threat for dexterity. Attempts are
      made to define and classify sarcopenia basing on the measurements of muscle mass
      where the examinations are conducted by the method of computed tomography,
      magnetic resonance imaging, absorptiometry of two X-ray beams of various
      energies, electric bioimpedance and anthropometric methods. The data gained in
      few studies conducted in order to estimate the reduction of muscle mass in
      patients with rheumatoid arthritis confirm the significant increase of sarcopenia
      occurence in this group. Procedure with rheumatoid arthritis covers primarily
      treatment of the inflammatory process with traditional and biological medicaments
      that modify the course of illness. Such treatment seems to diminish the risk of
      equal sarcopenia occurrence. The effectiveness of using anabolic medicaments and
      high protein diet has not been proved. Currently, regular physical activity
      including aerobic exercise and exercises with load is considered a good method of
      muscle mass loss prevention and a procedure in case of confirmed muscle mass
      loss.

PMID- 27717943
TI  - Pediatric pain management - what are we able to do in Polish emergency medical
      services?
AB  - Pain management in emergency medical care remains underestimated, especially in
      pediatric patients. This is due to neglecting the issue, lack of knowledge in the
      appropriate use of analgesics and finally- the fear of being criticized by
      physicians in hospital departments. Moreover, it is difficult to objectively
      assess a child with acute pain. Even experienced "adult" anesthesiologists wonder
      how to recognize if a child suffers strong pain or is just anxious. Many
      different pain scales are available and some of them may be used in emergency
      medical care.. The administration of analgesia used in children depends on the
      patient's age and competencies of the providers of medical emergency teams.
      Proper pain control and treatment brings immeasurable benefits to the psyche of
      the child and his guardian. The purpose of this review is to draw attention to
      the existing problem, present pain scales most suitable for specific groups of
      children as well as analgesia methods and to propose a simple pain management
      algorithm based on competencies of the various emergency medical services
      professional groups in Poland.

PMID- 27717944
TI  - [Intracranial arachnoid cysts in the clinical and radiological aspect].
AB  - Arachnoid cysts are intracranial pathologies in the space between the pia mater
      and the dura mater of the brain and cerebellum. Arachnoid cysts are derived from
      the arachnoidea mater, which while yielding to germination or splitting creates a
      space filled with liquid with a composition similar to cerebrospinal fluid. The
      aim of the study is to present possible clinical symptoms and radiological
      presentation of intracranial arachnoid cysts. The symptoms of intracranial
      arachnoid cysts are dependent on its size and location. Small cysts are often
      asymptomatic, while reaching a large size they have the effect of weight, which
      can lead to oppression and displacement of neurovascular structures, increased
      intracranial pressure, and therefore such cysts may be the reason for the
      occurrence of neurological symptoms. Increasing headaches, dizziness, nausea with
      or without vomiting, stiff neck may even feign subarachnoid hemorrhage (SAH). In
      neuroimaging arachnoid cysts account for 1-2% of all intracranial pathologic
      masses. The most common location of arachnoid cysts is down the middle and rear
      of the skull in natural bodies of cerebrospinal fluid. Arachnoid cysts have a
      high rate of change. They can undergo spontaneous growth as well as the reduction
      or disappearance. Headaches, nausea or vomiting, worsening of mood, mental status
      changes, ataxia, seizures, hearing loss may be symptoms of serious intracranial
      pathology requiring diagnosis based on neuroimaging.

PMID- 27717945
TI  - [What do we konw about the Zika virus?]
AB  - Zika virus (HIV) was first identified in 1947 and upto 2007 the infections in
      humans have been reported sporadically. Currently, the World Health Organization
      warns that the rapid spread of the virus Zika in both Americas and an increase in
      the number of children born with microcephaly in these regions begins to be a
      serious epidemiological problem. Known ways of spreading this RNA virus of the
      Flaviviridae family is: with blood, sexual, vertical and even breast feeding.
      Currently used diagnostic tests are not entirely perfect, as they can detect
      infections by other viruses in this group but they are available in Poland. The
      treatment of clinical sings of ZIKV as unusual, flu-like symptoms is symptomatic.
      Unfortunately, the most dangerous consequences of infection tend to be: a
      statement of microcephaly in children of mothers bitten by the mosquitoes in the
      areas of epidemy of Zika and symptoms of Guillain-Barre syndrome. For this
      reason, doctors of all specialties should have current knowledge of the
      diagnosis, prevention, treatment and consequences of this infection.

PMID- 27717946
TI  - Principle of serviceability and gratuitousness in transplantation?
AB  - INTRODUCTION: the issue of commercialization of transplantation analyses in the
      article. Attention is paid to the importance of transplantation as a method of
      treatment and saving human lives. AIM: the clarify the feasibility of the
      introduction of donation commercialization as an avenue to solve the shortage of
      donor organs and means of combating with black organ market and finding
      alternative avenues solving these problems, which are more morally acceptable for
      society is the aim of this article. MATERIALS AND METHODS: the experience of
      foreign countries has been analyses in the research. Additionally, we used data
      from international organizations, conclusions scientists and report of Global
      Financial Integrity in the research. RESULTS: it is impossible to solve most
      problems by means of paid donation. CONCLUSIONS: therapeutic organ and tissue
      cloning based on genetic technology is the best way out and solving ethical
      transplantation problems.

PMID- 27717947
TI  - [Predictive value of apolipoproteine E genotypes].
AB  - Apolipoprotein E is a transport protein, which by binding to lipids forms a
      lipoprotein particle. It is responsible for transport and redistribution of
      lipids between cells and tissues. Apolipoprotein E circulates in blood mainly as
      a component of VLDL (very low density lipoproteins) HDL (high density
      lipoproteins) chylomicrons and chylomicron remnants. It assists in the flow of
      cholesterol from peripheral cells to extracellular space. Apolipoprotein E is one
      of the most studied apolipoproteins. There are three isoforms of this protein:
      E2, E3 and E4. Six polymorphic variants are defined by of the ApoE gene. Isoforms
      vary in their ability to bind to receptors for ApoE and LDL (low density
      lipoproteins) and affinity to lipoproteins. This is why we observe different
      metabolic responses in patients with various isoforms. The ApoE4 variant
      correlates with higher level of cholesterol in blood and thus with increased risk
      of atherosclerosis progression. Apolipoprotein E plays a key role in a wide range
      of actions. It is associated with lipids metabolism dysfunction which leads to
      cardiovascular diseases and also with neurodegenerative diseases of the central
      nervous system. In addition to classical methods of cardiac prevention, genetic
      tests should be performed more commonly. This could be useful in better
      evaluation of predisposition to pathological processes.

PMID- 27717948
TI  - [Erectile dysfunction - treatment with substances of natural origin].
AB  - The article discusses erectile dysfunction (ED) with the special emphasis on
      epidemiology, as well as the currently available medical treatments. Describing
      treatment methods authors paid special attention to natural therapies (as Panax
      ginseng, Tribulus terrestris, Vaccinium macrocarpon), because taking into
      consideration their safety profile, they appear to be an important alternative to
      therapies with synthetic molecules. From substances of natural origin, extract
      from the fruit of Tribulus terrestris ranks itself high on in collation at the
      end. The results of most clinical trials and experiments clearly demonstrate its
      effectiveness in improving sexual function in men.

PMID- 27717949
TI  - The impact of the legal regime of intellectual property protection in the
      pharmaceutical market.
AB  - INTRODUCTION: the functioning of the healthcare industry in any country is
      impossible without providing enough medicines for patient care. This problem can
      best be resolved only when the majority of drugs, especially vital, will be made
      at national plants (industry). In this context, competition from generic drugs is
      the most optimal strategy to reduce drug's prices. AIM: the paper should examine
      how the legal regime of intellectual property affects the availability of
      medicines for people and identify ways of supporting breakthrough inventions and
      counter ?unreal innovations?. MATERIALS AND METHODS: for the purpose of study
      were generalized information from the scientific journals of medical and legal
      perspective, monographs by using a set of scientific methods. Namely under
      systematic approach have been analyzed the problems of pharmaceutical market,
      ways of producing generic and original drugs. Comparative legal method was useful
      for learning features of flexible mechanisms of the TRIPS Agreement and market
      regulation of medicines in the world. RESULTS: based on the research was found
      that developed countries with strong pharmaceutical industry are interested in
      maximizing the protection of intellectual property rights, including importing
      countries. Flexible mechanisms of the TRIPS Agreement can be useful for
      developing countries. CONCLUSIONS: thus, successful development of pharmaceutical
      industry and health care should be accompanied by the following measures: -
      improvement of public health must be recognized as a main task of government
      policy; - substantial state support aimed at increasing the availability of drugs
      in the domestic market and the strengthening of export potential; - decrease
      patent protection of medicines and stimulate market launch of generic copies.

PMID- 27717950
TI  - Eosinophilic cystitis and cholangitis - systemic disease triggered by
      mycobacterium tuberculosis?
AB  - Eosinophilic cystitis (EC) is a rare inflammatory disorder of the urinary tract
      characterized by infiltration of bladder with eosinophils. The cause remains
      unclear, immunological mechanisms have been implicated in pathogenesis. Potential
      etiological factors include: tumors, allergy, parasitic infections, trauma. The
      disease may have a variable course, from a mild self-limiting, through common
      symptoms like: dysuria, hematuria, abdominal pain, tumor, to severe renal
      failure, with eosinophilic infiltration of the other organs and systemic
      complications. Treatment depending on disease severity and etiology is
      pharmacological and/or surgical. Here we report a case of a previously healthy 16
      year old girl with inflammatory tumor in the liver hilum infiltrating
      extrahepatic biliary tract who developed three months later haematuria with acute
      dysuric signs and renal failure. Based on histopathological findings diagnosis of
      eosinophilic cystitis was established. Tests for Mycobacterium tuberculosis were
      positive. To our knowledge, EC association with cholangitis and tuberculosis have
      never been reported before.

PMID- 27717951
TI  - [Does the presence of an obstructive sleep apnea change the indications for the
      pacemaker implantation? - case raports].
AB  - The obstructive sleep apnea (OSA) is a mortality risk factor of the
      cardiovascular system diseases. One of the elements of this relationship is the
      occurrence of nocturnal cardiac arrhythmias. The arrhytmias in question are
      resistant to drug therapy so it is suggested to consider electrotherapy. However,
      the coexistence of OSA and thus recurrent episodes of nocturnal hypoxia, may have
      significant impact on the diagnosis and the treatment applied as shown in the
      following cases. In some cases, the decision of electrotherapy should be preceded
      by the use of therapy with continuous positive airway pressure (CPAP).

PMID- 27717952
TI  - Reversible complete atrioventricular block in patient with wegener's
      granulomatosis - a report on fortunate outcome with long term follow-up.
AB  - Reversible complete atrioventricular block in patient with Wegener's
      granulomatosis - a report on a positive outcome with long term follow-up.
      Atrioventricular (AV) block is a rare complication of Wegener's granulomatosis
      (WG), thus there are no standards of management in such cases. We present a case
      of a patient with a dual-chamber pacemaker (DDD) implanted due to complete AV
      block in the course of Wegener's granulomatosis (WG). An immunosuppressive
      therapy resulted in the resolution of non-cardiac and AV conduction disorders.
      The diagnostic functions of the pacemaker enabled us to evaluate AV conduction
      over a five-year follow-up period. The resolution of AV conduction disorders,
      which accompanied WG remission, suggests that careful monitoring with temporary
      cardiac pacing may be considered in some patients before permanent pacemaker
      implantation.

PMID- 27717953
TI  - The usefulness of free dicom viewers in rhinologic practice.
AB  - : Indroduction: The planning of the course of surgery in patients with paranasal
      sinus disorders requires the meticulous evaluation of computed tomography (CT)
      scans. However, ENT doctors still often receive unsatisfactory DICOM images,
      which require multiplanar reconstruction (MPR). THE AIM: The objective of the
      present study was to evaluate and test DICOM viewers with MPR function currently
      available on the Internet for free. MATERIAL AND METHODS: Detailed Internet
      searches and analysis of databases were carried out to find the maximum number of
      browsers. Available software was downloaded to assess, qualitatively and
      quantitatively, the parameters and functions useful in rhinologic practice.
      Additionally, a questionnaire was developed in order to ascertain the
      expectations and habits of ENT doctors in relation to DICOM browsers and CT scan
      evaluation. RESULTS AND CONCLUSIONS: Among the hundreds of browsers, 17 programs
      were chosen to be included in the final comparison. The outcomes of the survey
      proved that many free DICOM tools are effective alternatives to commercially
      available programs. However, the results do not enable us to predict precisely
      which tool will meet the needs of each physician. The survey among ENT doctors
      highlighted their limited awareness of software with MPR functions, in particular
      those that scored best in the test.

PMID- 27717954
TI  - Specific Features of Executive Dysfunction in Alzheimer-Type Mild Dementia Based
      on Computerized Cambridge Neuropsychological Test Automated Battery (CANTAB) Test
      Results.
AB  - BACKGROUND The primary manifestation of Alzheimer's disease (AD) is decline in
      memory. Dysexecutive symptoms have tremendous impact on functional activities and
      quality of life. Data regarding frontal-executive dysfunction in mild AD are
      controversial. The aim of this study was to assess the presence and specific
      features of executive dysfunction in mild AD based on Cambridge
      Neuropsychological Test Automated Battery (CANTAB) results. MATERIAL AND METHODS
      Fifty newly diagnosed, treatment-naive, mild, late-onset AD patients (MMSE >=20,
      AD group) and 25 control subjects (CG group) were recruited in this prospective,
      cross-sectional study. The CANTAB tests CRT, SOC, PAL, SWM were used for in-depth
      cognitive assessment. Comparisons were performed using the t test or Mann-Whitney
      U test, as appropriate. Correlations were evaluated by Pearson r or Spearman R.
      Statistical significance was set at p<0.05. RESULTS AD and CG groups did not
      differ according to age, education, gender, or depression. Few differences were
      found between groups in the SOC test for performance measures: Mean moves
      (minimum 3 moves): AD (Rank Sum=2227), CG (Rank Sum=623), p<0.001. However, all
      SOC test time measures differed significantly between groups: SOC Mean subsequent
      thinking time (4 moves): AD (Rank Sum=2406), CG (Rank Sum=444), p<0.001.
      Correlations were weak between executive function (SOC) and episodic/working
      memory (PAL, SWM) (R=0.01-0.38) or attention/psychomotor speed (CRT) (R=0.02
      0.37). CONCLUSIONS Frontal-executive functions are impaired in mild AD patients.
      Executive dysfunction is highly prominent in time measures, but minimal in
      performance measures. Executive disorders do not correlate with a decline in
      episodic and working memory or psychomotor speed in mild AD.

PMID- 27717956
TI  - Natural variations in stearoyl-acp desaturase genes affect the conversion of
      stearic to oleic acid in maize kernel.
AB  - KEY MESSAGE: We identified 11 SAD genes, and mined their natural variations
      associated with the conservation of stearic to oleic acid, especially ZmSAD1
      supported by both the QTL and an expression QTL. Maize oil is generally regarded
      as a healthy vegetable oil owing to its low abundance of saturated fatty acids.
      Stearoyl-ACP desaturase (SAD) is a key rate-limiting enzyme for the conservation
      of stearic (C18:0) to oleic (C18:1) acid. Here, 11 maize SAD genes were
      identified to have more divergent functions than Arabidopsis SAD genes. The
      genomic regional associations in a maize panel including 508 inbred lines
      identified 6 SAD genes significantly associated (P < 0.01) with the C18:0/C18:1
      ratio or the level of C18:0 or C18:1, one gene of which co-localized with a
      quantitative trait locus (QTL) and 5 of which co-localized with an expression
      QTL. ZmSAD1, supported by both the QTL and an expression QTL, had the largest
      effect on C18:0/C18:1. One nonsynonymous single-nucleotide polymorphism in exon 3
      and one 5-bp insertion/deletion in the 3' untranslated region were further shown
      to contribute to the natural variation in C18:0/C18:1 according to ZmSAD1-based
      association mapping. Finally, selection tests of ZmSAD1 in teosinte, regular
      maize, and high-oil maize indicated that ZmSAD1 was not a selection target during
      the process of maize domestication and high-oil maize development. These results
      will guide the manipulation of the ratio between saturated and unsaturated fatty
      acids in maize.

PMID- 27717955
TI  - From Mendel's discovery on pea to today's plant genetics and breeding :
      Commemorating the 150th anniversary of the reading of Mendel's discovery.
AB  - KEY MESSAGE: This work discusses several selected topics of plant genetics and
      breeding in relation to the 150th anniversary of the seminal work of Gregor
      Johann Mendel. In 2015, we celebrated the 150th anniversary of the presentation
      of the seminal work of Gregor Johann Mendel. While Darwin's theory of evolution
      was based on differential survival and differential reproductive success,
      Mendel's theory of heredity relies on equality and stability throughout all
      stages of the life cycle. Darwin's concepts were continuous variation and "soft"
      heredity; Mendel espoused discontinuous variation and "hard" heredity. Thus, the
      combination of Mendelian genetics with Darwin's theory of natural selection was
      the process that resulted in the modern synthesis of evolutionary biology.
      Although biology, genetics, and genomics have been revolutionized in recent
      years, modern genetics will forever rely on simple principles founded on pea
      breeding using seven single gene characters. Purposeful use of mutants to study
      gene function is one of the essential tools of modern genetics. Today, over 100
      plant species genomes have been sequenced. Mapping populations and their use in
      segregation of molecular markers and marker-trait association to map and isolate
      genes, were developed on the basis of Mendel's work. Genome-wide or genomic
      selection is a recent approach for the development of improved breeding lines.
      The analysis of complex traits has been enhanced by high-throughput phenotyping
      and developments in statistical and modeling methods for the analysis of
      phenotypic data. Introgression of novel alleles from landraces and wild relatives
      widens genetic diversity and improves traits; transgenic methodologies allow for
      the introduction of novel genes from diverse sources, and gene editing approaches
      offer possibilities to manipulate gene in a precise manner.

PMID- 27717957
TI  - Early post-surgical cognitive dysfunction is a risk factor for mortality among
      hip fracture hospitalized older persons.
AB  - : This study investigates the relationship between cognitive dysfunction or
      delirium detected in the early post-surgical phase and the 1-year mortality among
      514 hip fracture hospitalized older persons. Patients with early cognitive
      dysfunction or delirium experienced a 2-fold increased mortality risk. Early post
      operative cognitive dysfunction and delirium are negative prognostic factors for
      mortality. BACKGROUND AND PURPOSE: Premorbid cognitive impairment and dementia in
      older individuals negatively affect functional recovery after hip fracture.
      Additionally, post-operative delirium is an established risk factor for negative
      outcomes among hip fracture patients. While the majority of hip fracture patients
      experience minor post-surgical cognitive dysfunction, the prognostic value of
      this phenomenon is unknown. Therefore, we investigated the relationship between
      minor cognitive dysfunction or delirium detected in the early post-surgical phase
      and the 1-year mortality after index hip fracture. SUBJECTS AND METHODS: We
      enrolled 514 patients with hip fracture (77.4 % women), aged 65 years or older
      (mean age 83.1 +/- 7.3 years), who underwent surgical hip fracture repair.
      Patients were assessed daily from the second to the fourth post-operative day and
      at 3, 6, and 12 months thereafter. All participants underwent comprehensive
      assessment, including detection of delirium by using the confusion assessment
      method and evaluation of cognitive function by using mini-mental state
      examination (MMSE; score range 0 to 30, with lower scores indicating poorer
      performance). In the absence of delirium, post-surgical cognitive dysfunction was
      defined as having low performance on MMSE. Vital status of 1 year after the index
      fracture and date of death were gathered from local registries. RESULTS: The
      observed 1-year mortality rate was 14.8 %. Men were more likely to die than women
      within 1 year of the index fracture (p < 0.01). Compared to participants with
      better cognitive performance, those with MMSE < 24, as well as those with
      delirium in the post-operative phase, showed a significantly higher 1-year
      mortality rate (23.3 versus 17.9 and 8.1 %, respectively). Independent of age and
      sex, post-operative cognitive dysfunction as well as delirium was both associated
      with a 2-fold increased mortality risk. CONCLUSIONS: The presence of minor
      cognitive dysfunction in the early post-surgical phase is a negative prognostic
      factor for mortality among elderly hip fracture patients. The burden of minor
      cognitive dysfunction is likely superimposed on that of delirium in subgroups of
      frail patients.

PMID- 27717959
TI  - Endotrophin, a multifaceted player in metabolic dysregulation and cancer
      progression, is a predictive biomarker for the response to PPARgamma agonist
      treatment.
AB  - Endotrophin is a cleavage product derived from the collagen VI(alpha3) chain.
      Collagen VI is expressed in a number of different tissues, but adipose tissue is
      a particularly prominent source for this extracellular matrix constituent. Mice
      lacking collagen VI are metabolically healthier due to reduced fibrosis in
      adipose tissue. Endotrophin seems to be one of the key players of collagen VI
      mediated signalling effects, including its pro-fibrotic nature and
      chemoattractant properties for macrophages, while also playing an important role
      in cancer progression and the chemoresistance of tumour cells. The glucose
      lowering class of thiazolidinediones (TZDs) that mediate their action through the
      nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma also
      exerts important effects on endotrophin by reducing the transcription of parental
      collagen VI molecules. As with many other pharmacological interventions, there is
      a range of responses observed in a diabetic patient population. In this issue of
      Diabetologia, Karsdal and colleagues (DOI: 10.1007/s00125-016-4094-1 )
      demonstrate that baseline endotrophin levels offer excellent predictive values to
      indicate individuals who will show an optimised response to TZDs with respect to
      the lowering of HbA1c and reduced risk of adverse side effects. The
      identification of a predictive biomarker for optimal responders is an important
      step in highlighting the continued viability of TZDs as an effective glucose
      lowering class of compounds.

PMID- 27717960
TI  - Dementia onset, incidence and risk in type 2 diabetes: a matched cohort study
      with the Fremantle Diabetes Study Phase I.
AB  - AIMS/HYPOTHESIS: The study aimed to assess the incidence, age of onset, survival
      and relative hazard of dementia in well-categorised community-based patients with
      type 2 diabetes compared with a matched cohort of individuals without diabetes.
      METHODS: A longitudinal observational study was undertaken involving 1291
      participants with type 2 diabetes from the Fremantle Diabetes Study and 5159
      matched residents without documented diabetes. Linkage with health-related
      databases was used to detect incident dementia. Relative hazards were assessed
      using both cause-specific and subdistribution proportional hazards models.
      RESULTS: During 13.8 +/- 5.8 years of follow-up, incident dementia occurred in
      13.9% and 12.4% of the groups of participants with and without diabetes,
      respectively (p = 0.15). With type 2 diabetes, the incidence of dementia was
      higher (incidence rate ratio [IRR] 1.28, 95% CI 1.08, 1.51), as was the competing
      risk of death (IRR 1.50, 95% CI 1.38, 1.64). The ages when dementia was first
      recorded and when death with dementia occurred were both earlier with diabetes,
      by 1.7 (95% CI 0.6, 2.9) and 2.3 (95% CI 1.1, 3.6) years, respectively (both p <=
      0.004). Type 2 diabetes was associated with an adjusted subdistribution HR of
      1.18 (95% CI 1.00, 1.39), and a cause-specific HR of 1.51 (95% CI 1.27, 1.78) for
      all-cause dementia. CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated
      with an increased incidence of dementia, and dementia onset occurs at a younger
      age. The relative hazards of both dementia and premature mortality are increased
      and, as a consequence, the increased risk of dementia in type 2 diabetes is not
      as marked as suggested by cause-specific HRs.

PMID- 27717958
TI  - Molecular modelling and molecular dynamics of CFTR.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a
      member of the ATP-binding cassette (ABC) transporter superfamily that functions
      as an ATP-gated channel. Considerable progress has been made over the last years
      in the understanding of the molecular basis of the CFTR functions, as well as
      dysfunctions causing the common genetic disease cystic fibrosis (CF). This review
      provides a global overview of the theoretical studies that have been performed so
      far, especially molecular modelling and molecular dynamics (MD) simulations. A
      special emphasis is placed on the CFTR-specific evolution of an ABC transporter
      framework towards a channel function, as well as on the understanding of the
      effects of disease-causing mutations and their specific modulation. This in
      silico work should help structure-based drug discovery and design, with a view to
      develop CFTR-specific pharmacotherapeutic approaches for the treatment of CF in
      the context of precision medicine.

PMID- 27717962
TI  - Retraction Note to: Enhancement of the catalytic activity of ferulic acid
      decarboxylase from Enterobacter sp. Px6-4 through random and site-directed
      mutagenesis.

PMID- 27717963
TI  - A unique intracellular compartment formed during the oligotrophic growth of
      Rhodococcus erythropolis N9T-4.
AB  - Rhodococcus erythropolis N9T-4, isolated from stored crude oil, shows extremely
      oligotrophic features and can grow on a basal medium without any additional
      carbon, nitrogen, sulfur, and energy sources, but requires CO2 for its
      oligotrophic growth. Transmission electron microscopic observation showed that a
      relatively large and spherical compartment was observed in a N9T-4 cell grown
      under oligotrophic conditions. In most cases, only one compartment was observed
      per cell, but in some cases, it was localized at each pole of the cell,
      suggesting that it divides at cell division. We termed this unique bacterial
      compartment an oligobody. The oligobody was not observed or very rarely observed
      in small sizes under nutrient rich conditions, whereas additional carbon sources
      did not affect oligobody formation. Energy dispersive X-ray spectroscopy analysis
      revealed remarkable peaks corresponding to phosphorus and potassium in the
      oligobody. The oligobodies in N9T-4 cells could be stained by Toluidine blue,
      suggesting that the oligobody is composed of inorganic polyphosphate and is a
      type of acidocalcisome. Two genes-encoding polyphosphate kinases, ppk1 and ppk2,
      were found in the N9T-4 genome: ppk1 disruption caused a negative effect on the
      formation of the oligobody. Although it was suggested that the oligobody plays an
      important role for the oligotrophic growth, both ppk-deleted mutants showed the
      same level of oligotrophic growth as the wild-type strain.

PMID- 27717964
TI  - Incubation of innovative methanogenic communities to seed anaerobic digesters.
AB  - The methanogenic communities in alternative inocula and their potential to
      increase CH4 production in mesophilic and psychrophilic dairy manure-based
      anaerobic digesters were examined. Quantitative-PCR and terminal restriction
      fragment length polymorphism (T-RFLP) profiles were used to determine archaeal
      and methanogenic community changes when three inocula (wetland sediment (WS),
      landfill leachate (LL), and mesophilic digestate (MD)) were incubated at 15, 25,
      and 35  degrees C for 91 and 196 days. After each incubation period, the inocula
      were used in biochemical methane potential (BMP) tests at the incubation
      temperatures. There was no significant correlation between inoculum mcrA gene
      copy numbers and CH4 produced in BMP tests, suggesting that population size was
      not a distinguishing characteristic for predicting CH4 production. Archaeal
      composition in LL and WS reactors generally converged with MD reactors after
      incubation at 25 and 35  degrees C for 196 days. These MD reactors had high
      relative abundance of TRF 302, likely Methanosaetaceae, and low acetic acid (0.62
      1.61 mM). At 15  degrees C incubation, most reactors were associated with high
      acetic acid (1.61-133.6 mM) and dominated by TRF 199, likely Methanosarcinaceae.
      The LL reactor incubated at 25  degrees C for 91 days had higher relative
      abundance of TRF 199 and produced significantly higher CH4 than WS and MD
      reactors in BMP test. In the future, it may be possible to create enrichment
      cultures that favor particular methanogens and use them as inoculum to benefit
      digesters at low mesophilic temperatures. Our data provides evidence that
      tailoring the archaeal community could benefit digesters operating under
      different conditions.

PMID- 27717965
TI  - Biosynthesis of nanoparticles of metals and metalloids by basidiomycetes.
      Preparation of gold nanoparticles by using purified fungal phenol oxidases.
AB  - The work shows the ability of cultured Basidiomycetes of different taxonomic
      groups-Lentinus edodes, Pleurotus ostreatus, Ganoderma lucidum, and Grifola
      frondosa-to recover gold, silver, selenium, and silicon, to elemental state with
      nanoparticles formation. It examines the effect of these metal and metalloid
      compounds on the parameters of growth and accumulation of biomass; the optimal
      cultivation conditions and concentrations of the studied ion-containing compounds
      for recovery of nanoparticles have been identified. Using the techniques of
      transmission electron microscopy, dynamic light scattering, X-ray fluorescence
      and X-ray phase analysis, the degrees of oxidation of the bioreduced elements,
      the zeta-potential of colloidal solutions uniformity, size, shape, and location
      of the nanoparticles in the culture fluid, as well as on the surface and the
      inside of filamentous hyphae have been determined. The study has found the part
      played by homogeneous chromatographically pure fungal phenol-oxidizing enzymes
      (laccases, tyrosinases, and Mn-peroxidases) in the recovery mechanism with
      formation of electrostatically stabilized colloidal solutions. A hypothetical
      mechanism of gold(III) reduction from HAuCl4 to gold(0) by phenol oxidases with
      gold nanoparticles formation of different shapes and sizes has been introduced.

PMID- 27717966
TI  - The role of sponge-bacteria interactions: the sponge Aplysilla rosea challenged
      by its associated bacterium Streptomyces ACT-52A in a controlled aquarium system.
AB  - Sponge-associated bacteria play a critical role in sponge biology, metabolism and
      ecology, but how they interact with their host sponges and the role of these
      interactions are poorly understood. This study investigated the role of the
      interaction between the sponge Aplysilla rosea and its associated
      actinobacterium, Streptomyces ACT-52A, in modifying sponge microbial diversity,
      metabolite profile and bioactivity. A recently developed experimental approach
      that exposes sponges to bacteria of interest in a controlled aquarium system was
      improved by including the capture and analysis of secreted metabolites by the
      addition of an absorbent resin in the seawater. In a series of controlled
      aquaria, A. rosea was exposed to Streptomyces ACT-52A at 106 cfu/ml and monitored
      for up to 360 h. Shifts in microbial communities associated with the sponges
      occurred within 24 to 48 h after bacterial exposure and continued until 360 h, as
      revealed by TRFLP. The metabolite profiles of sponge tissues also changed
      substantially as the microbial community shifted. Control sponges (without added
      bacteria) and Streptomyces ACT-52A-exposed sponges released different metabolites
      into the seawater that was captured by the resin. The antibacterial activity of
      compounds collected from the seawater increased at 96 and 360 h of exposure for
      the treated sponges compared to the control group due to new compounds being
      produced and released. Increased antibacterial activity of metabolites from
      treated sponge tissue was observed only at 360 h, whereas that of control sponge
      tissue remained unchanged. The results demonstrate that the interaction between
      sponges and their associated bacteria plays an important role in regulating
      secondary metabolite production.

PMID- 27717961
TI  - Malignant inflammation in cutaneous T-cell lymphoma-a hostile takeover.
AB  - Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of
      chronically inflamed skin lesions containing malignant T cells. Early disease
      presents as limited skin patches or plaques and exhibits an indolent behavior.
      For many patients, the disease never progresses beyond this stage, but in
      approximately one third of patients, the disease becomes progressive, and the
      skin lesions start to expand and evolve. Eventually, overt tumors develop and the
      malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and
      visceral organs, often with a fatal outcome. The transition from early indolent
      to progressive and advanced disease is accompanied by a significant shift in the
      nature of the tumor-associated inflammation. This shift does not appear to be an
      epiphenomenon but rather a critical step in disease progression. Emerging
      evidence supports that the malignant T cells take control of the inflammatory
      environment, suppressing cellular immunity and anti-tumor responses while
      promoting a chronic inflammatory milieu that fuels their own expansion. Here, we
      review the inflammatory changes associated with disease progression in CTCL and
      point to their wider relevance in other cancer contexts. We further define the
      term "malignant inflammation" as a pro-tumorigenic inflammatory environment
      orchestrated by the tumor cells and discuss some of the mechanisms driving the
      development of malignant inflammation in CTCL.

PMID- 27717967
TI  - A new assay for the simultaneous identification and differentiation of Klebsiella
      oxytoca strains.
AB  - Klebsiella oxytoca is the second most frequently identified species of Klebsiella
      isolated from hospitalized patients. Klebsiella spp. is difficult to identify
      using conventional methods and is often misclassified in clinical microbiology
      laboratories. K. oxytoca is responsible for an increasing number of multi
      resistant infections in hospitals because of insufficient detection and
      identification. In this study, we propose a new simple method called pehX-LM
      PCR/XbaI, which simultaneously indicates K. oxytoca species and genotype by the
      fingerprint pattern. The pehX-LM PCR/XbaI is a combination of the following two
      methods: species-specific amplification of pehX gene and non-specific
      amplification of short restriction fragments by the LM PCR method. The
      specificity and the discrimination power of the pehX-LM PCR/XbaI method were
      determined by typing 209 K. oxytoca strains (included 9 reference strains), 28 K.
      pneumoniae, and other 25 strains belonging to the Enterobacteriaceae. The typing
      results were confirmed by the PCR melting profile method. Unlike the known
      fingerprinting methods, the pehX-LM PCR/XbaI leads to a clear pattern (approx. 3
      5 bands) with a sufficient, relatively high discriminatory power. As a result,
      the time and cost of a single analysis are lower. The method can be used both in
      clinical and environmental research.

PMID- 27717968
TI  - Beneficial microorganisms for honey bees: problems and progresses.
AB  - Nowadays, honey bees are stressed by a number of biotic and abiotic factors which
      may compromise to some extent the pollination service and the hive productivity.
      The EU ban of antibiotics as therapeutic agents against bee pathogens has
      stimulated the search for natural alternatives. The increasing knowledge on the
      composition and functions of the bee gut microbiota and the link between a
      balanced gut microbiota and health status have encouraged the research on the use
      of gut microorganisms to improve bee health. Somehow, we are assisting to the
      transfer of the "probiotic concept" into the bee science. In this review, we
      examine the role of the honey bee gut microbiota in bee health and critically
      describe the available applications of beneficial microorganisms as pest control
      agents and health support. Most of the strains, mainly belonging to the genera
      Lactobacillus, Bifidobacterium and Bacillus, are isolated from honey bee crop or
      gut, but some applications involve environmental strains or formulation for
      animal and human consumption. Overall, the obtained results show the favourable
      effect of applied microbial strains on bee health and productivity, in particular
      if strains of bee origin are used. However, it is actually not yet possible to
      conclude whether this strategy will ever work. In particular, many aspects
      regarding the overall setup of the experiments, the dose, the timing and the
      duration of the treatment need to be optimized, also considering the
      microbiological safety of the hive products (i.e. pollen and honey). In addition,
      a deep investigation about the effect on host immunity and physiology is
      envisaged. Lastly, the final users of the formulations, i.e. beekeepers, should
      be taken into account for the achievement of high-quality, cost-effective and
      easy-to-use products.

PMID- 27717969
TI  - Multiple origins of gigantism in stem baleen whales.
AB  - Living baleen whales (Mysticeti) include the world's largest animals to have ever
      lived-blue whales (Balaenoptera musculus) can reach more than 30 m. However, the
      gigantism in baleen whales remains little explored. Here, we compiled all
      published stem mysticetes from the Eocene and Oligocene and then mapped the
      estimated body size onto different phylogenies that suggest distinct evolutionary
      histories of baleen whales. By assembling all known stem baleen whales, we
      present three novel findings in early mysticete evolution. Results show that,
      regardless of different phylogenetic scenarios, large body size (more than 5-m
      long) evolved multiple times independently in their early evolutionary history.
      For example, the earliest known aetiocetid (Fucaia buelli, 33-31 Ma) was small in
      size, about 2 m, and a later aetiocetid (Morawanocetus-like animal, 26-23 Ma) can
      reach 8-m long-almost four times the size of Fucaia buelli-suggesting an
      independent gigantism in the aetiocetid lineage. In addition, our reconstruction
      of ancestral state demonstrates that the baleen whales originated from small body
      size (less than 5 m) rather than large body size as previously acknowledged.
      Moreover, reconstructing the evolution of body size in stem baleen whales
      suggests that the initial pulse of mysticete gigantism started at least back to
      the Paleogene and in turn should help to understand the origin, pattern, and
      process of the extreme gigantism in the crown baleen whales. This study
      illustrates that Cope's rule is insufficient to explain the evolution of body
      size in a group that comprises the largest animals in the history of life,
      although currently the lack of exact ancestor-descendant relationships remains to
      fully reveal the evolutionary history of body size.

PMID- 27717971
TI  - Response to Cohen et al. (2016) regarding response to Druwe and Burgoon.

PMID- 27717970
TI  - Maintenance of drug metabolism and transport functions in human precision-cut
      liver slices during prolonged incubation for 5 days.
AB  - Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be
      used in acute toxicity studies. However, a rapid decline in metabolic enzyme
      activity limits their use in studies that require a prolonged xenobiotic
      exposure. The aim of the study was to extend the viability and function of hPCLS
      to 5 days of incubation. hPCLS were incubated in two media developed for long
      term culture of hepatocytes, RegeneMed(r), and Cellartis(r), and in the standard
      medium WME. Maintenance of phase I and II metabolism was studied both on gene
      expression as well as functional level using a mixture of CYP isoform-specific
      substrates. Albumin synthesis, morphological integrity, and glycogen storage was
      assessed, and gene expression was studied by transcriptomic analysis using
      microarrays with a focus on genes involved in drug metabolism, transport and
      toxicity. The data show that hPCLS retain their viability and functionality
      during 5 days of incubation in Cellartis(r) medium. Albumin synthesis as well as
      the activity and gene expression of phase I and II metabolic enzymes did not
      decline during 120-h incubation in Cellartis(r) medium, with CYP2C9 activity as
      the only exception. Glycogen storage and morphological integrity were maintained.
      Moreover, gene expression changes in hPCLS during incubation were limited and
      mostly related to cytoskeleton remodeling, fibrosis, and moderate oxidative
      stress. The expression of genes involved in drug transport, which is an important
      factor in determining the intracellular xenobiotic exposure, was also unchanged.
      Therefore, we conclude that hPCLS cultured in Cellartis(r) medium are a valuable
      human ex vivo model for toxicological and pharmacological studies that require
      prolonged xenobiotic exposure.

PMID- 27717973
TI  - [The scaphoid and rheumatoid arthritis : Classification by retrospective X-ray
      analysis].
AB  - BACKGROUND: Early destruction of the wrist in rheumatoid arthritis is common and
      often progressive. Even in times of improved and standardized medical treatment
      this cannot always be prevented. OBJECTIVES: A limited range of motion, pain,
      reduced grip-force, and aesthetic deficits of the wrist can impair the daily life
      of patients. There is an additional risk for destruction of the surrounding soft
      tissue and adjoining joints of the upper extremity. RESULTS: Destruction of wrist
      in rheumatoid arthritis is multifactorial and is localized in many different
      structures of the wrist. In this context, scaphoid and periscaphoid structures
      are of interest. Data were gathered in a retrospective study of the wrist X-rays
      of patients with rheumatoid arthritis. The possible consequences for operative
      options are described.

PMID- 27717974
TI  - Response to letter to the editor.

PMID- 27717972
TI  - Assessment of demographic and pathoanatomic risk factors in recurrent
      patellofemoral instability.
AB  - PURPOSE: The WARPS/STAID classification employs clinical assessment of presenting
      features and anatomic characteristics to identify two distinct subsets of
      patients within the patellofemoral instability population. The purpose of this
      study was to further define the specific demographics and the prevalence of risky
      pathoanatomies in patients classified as either WARPS or STAID presenting with
      recurrent patellofemoral instability. A secondary purpose was to further validate
      the WARPS/STAID classification with the Banff Patella Instability Instrument
      (BPII), the Marx activity scale and the Patellar Instability Severity Score
      (ISS). METHODS: A convenience sample of 50 patients with recurrent patellofemoral
      instability, including 25 WARPS and 25 STAID subtype patients, were assessed.
      Clinical data were collected including assessment of demographic risk factors
      (sex, BMI, bilaterality of symptoms, affected limb side and age at first
      dislocation) and pathoanatomic risk factors (TT-TG distance, patella height,
      patellar tilt, grade of trochlear dysplasia, Beighton score and rotational
      abnormalities of the tibia or femur). Patients completed the BPII and the Marx
      activity scale. The ISS was calculated from the clinical assessment data.
      Patients were stratified into the WARPS or STAID subtypes for comparative
      analysis. An independent t test was used to compare demographics, the
      pathoanatomic risk factors and subjective measures between the groups. Convergent
      validity was tested with a Pearson r correlation coefficient between the
      WARPS/STAID and ISS scores. RESULTS: Demographic risk factors statistically
      associated with a WARPS subtype included female sex, age at first dislocation and
      bilaterality. Pathoanatomic risk factors statistically associated with a WARPS
      subtype included trochlear dysplasia, TT-TG distance, generalized ligamentous
      laxity, patellar tilt and rotational abnormalities. The independent t test
      revealed a significant difference between the ISS scores: WARPS subtype (M = 4.4,
      SD = 1.1) and STAID subtype (M = 2.5, SD = 1.5); t(48) = 5.2, p < 0.001. The
      relationship between the WARPS/STAID and the ISS scores, measured using a Pearson
      r correlation coefficient, demonstrated a strong relationship: r = -0.61, n = 50,
      p < 0.001. CONCLUSIONS: This study has demonstrated statistically significant
      evidence that certain demographics and pathoanatomies are more prevalent in each
      of the WARPS and STAID patellofemoral instability subtypes. There was no
      difference in quality-of-life or activity level between the subtypes. The
      WARPS/STAID score demonstrated convergent validity to the ISS and divergent
      validity to the BPII score and the Marx activity scale. This study has further
      validated both the WARPS/STAID classification and the ISS of patients that
      present with recurrent patellofemoral instability. LEVEL OF EVIDENCE: III.

PMID- 27717975
TI  - Diagnostic accuracy of 3T conventional shoulder MRI in the detection of the long
      head of the biceps tendon tears associated with rotator cuff tendon tears.
AB  - OBJECTIVE: To evaluate the diagnostic performance (DP) of 3T (3 Tesla field
      strength) conventional shoulder magnetic resonance imaging (MRI) in detecting the
      long head of the biceps tendon (LHBT) tears in association with rotator cuff
      tendon tears. MATERIALS AND METHODS: This study included 80 consecutive patients
      who underwent arthroscopic surgery for rotator cuff tendon tears. Two
      radiologists independently evaluated the preoperative 3T shoulder MRI for the
      presence of LHBT tears. The DP of MRI was evaluated using the results of
      arthroscopy as the reference standard. We also evaluated the DP of several MR
      signs of LHBT in detection of partial LHBT tears. RESULTS: Arthroscopic
      examination revealed 35 partial and 5 complete tears. According to the results of
      evaluation by reviewers 1 and 2, shoulder MRI exhibited sensitivities of 77.14
      and 80 % and specificities of 71.11 and 73.33 % in detection of partial LHBT
      tears and sensitivities of 80 and 100 % and a specificity of 100% (both) in
      detection of complete LHBT tears. In detecting partial LHBT tears, increased T2
      signal intensity of the LHBT exhibited high sensitivities (reviewers 1 and 2;
      82.85 and 80 %, respectively) and the presence of intratendinous defects or C
      signs exhibited the highest specificities (reviewers 1 and 2; 95.55 and 93.33 %,
      respectively), followed by abnormalities in shape and outer margins of the LHBT
      (reviewers 1 and 2; 91.11 and 82 %; 91.11 and 86.66 %, respectively). CONCLUSION:
      Non-contrast-enhanced 3T shoulder MRI is potentially highly accurate in detection
      of complete LHBT tears, but moderately accurate in detection of partial LHBT
      tears.

PMID- 27717976
TI  - Coexisting sarcoidal granulomatous inflammation and diffuse tenosynovial giant
      cell tumor of the knee after a total knee replacement: a case report.
AB  - Sarcoidosis is a systemic inflammatory disorder characterized by non-caseating
      granulomas, predominantly involving lung, mediastinal lymph nodes and other
      organs. Synovium involvement is infrequent, and as far as we know, involvement of
      a periprosthetic membrane has not been reported in the English literature. Intra
      articular diffuse tenosynovial giant cell tumor ("conventional diffuse pigmented
      villonodular synovitis") is an uncommon, locally aggressive neoplasm with few
      previous case reports in which it arose in periprosthetic tissues after knee
      arthroplasty. We describe a unique case of an intraarticular mass next to a total
      knee prosthesis implanted 6 years ago in a patient with a history of pulmonary
      sarcoidosis. Clinically, this 67-year-old gentleman presented with progressive
      left knee pain, effusion and marked instability. MRI showed a large complex
      effusion with synovial thickening in the supra patella recess and the medial and
      lateral gutters. In addition, a large multilobulated mass with mixed low and high
      signal intensity was present in the posterior joint space, extending into the
      popliteal area. A two-stage operation was performed. Histologically, the mass
      from the posterior joint space showed characteristic features of diffuse
      tenosynovial giant cell tumor, while the synovium from the anterior compartment
      demonstrated sarcoidal granulomatous inflammation. Orthopaedic wear debris was
      found within the giant cells of these sarcoidal granulomata. The histologic
      features are different from those "usual" macrophage reactions to the particles
      of debris. In this article, we also included two optional links (highlighted in
      blue in the figures) to digital whole slide image (WSI), which allow the readers
      to navigate the entire microscope slides.

PMID- 27717977
TI  - Ring finger lumbrical origin strain: a case series with imaging findings.
AB  - Lumbrical strain is a relatively unknown hand injury. We report four cases of
      lumbrical origin strain involving the ring finger flexor tendons. Three patients
      sustained the injury during rock climbing and one while working with a
      jackhammer. In all cases, circumferential fluid around the flexor tendons of the
      ring finger was demonstrated on MRI and/or ultrasound at the distal palmar level
      at the "bare area," which is normally devoid of a synovial sheath. There is a
      paucity of information in the literature regarding this injury and its specific
      imaging features. Lack of awareness of this injury renders accurate diagnosis
      difficult.

PMID- 27717978
TI  - High-resolution ultrasound in the diagnosis of trigger finger and evaluation of
      response to steroid injection.
AB  - OBJECTIVE: No studies have reported the use of ultrasound for the evaluation of
      trigger finger after steroid injection. We evaluated the clinical features and
      ultrasound appearance of trigger finger before and after steroid injection under
      ultrasound guidance. MATERIALS AND METHODS: Thirty-eight digits with triggering
      were included. A single steroid injection into the tendon sheath was
      administered. Ultrasound findings and clinical symptoms, including pain,
      triggering, and the Quinnell score, were analyzed before injection and at 1 and 3
      weeks after injection. RESULTS: Ultrasound indicated that the thickness of the
      flexor tendons and the thickness of A1 pulleys were significantly greater in the
      trigger fingers than in controls before steroid injection. Three weeks after
      injection, these two parameters decreased, and there was no significant
      difference in the two parameters between the trigger finger and the controls. The
      visual analogue scales at 1 and 3 weeks after the injection were significantly
      lower than those before the injection. The Quinnell grading system scores
      significantly improved at 1 and 3 weeks after injection compared with the scores
      before injection. Moreover, a tendency was seen for the more clinically severe
      cases to show more swelling of the tendon and pulley. CONCLUSION: In conclusion,
      ultrasound assessments could reveal that the thickened A1 pulley and flexor
      tendon significantly improved after steroid injection, which enables us to
      confirm the therapeutic effects of the steroid injection. Therefore, ultrasound
      assessments can be a useful adjunct to understand the response to treatment with
      the steroid injection.

PMID- 27717979
TI  - Abdominal manifestations of fishbone perforation: a pictorial essay.
AB  - PURPOSE: The present article provides an overview of the spectrum of abdominal
      presentations of fishbone (FB) ingestion and its complications. METHODS: In image
      data from 9 patients, FB perforations were found in different levels of the
      gastrointestinal tract (GIT), including duodenal, jejunal, and sigmoid
      perforations; in 4 asymptomatic patients, FBs were observed in the mesentery,
      falciform ligament, and intestinal bowel. RESULTS: The main imaging features of
      FB perforation were focal gastric or intestinal wall thickening, fat stranding,
      bowel obstruction, ascites, localized pneumoperitoneum, intra-abdominal abscess,
      liver abscess, and a linear hyperdense structure in the abdominal cavity in the
      GIT or within a parenchymal organ often surrounded by inflammatory changes. Free
      pneumoperitoneum was rare. CONCLUSION: Although in most cases, a FB does not
      cause any serious complications, an inflammatory process and complications may
      occur when it perforates the stomach or bowel loops. Radiologists need to be
      aware of the possibility of FB perforation, especially in high-risk patients,
      because it is not always considered in the differential diagnosis by referring
      physicians and can mimic other inflammatory conditions and tumoral lesions.

PMID- 27717981
TI  - ?

PMID- 27717980
TI  - Quantitative analysis of the right auricle with 256-slice computed tomography.
AB  - PURPOSE: To quantitatively measure the morphology parameters of the right auricle
      with 256-slice multidetector computed tomography angiography (MDCTA) in healthy
      people. MATERIALS AND METHODS: A retrospective analysis of 200 patients who had
      undergone coronary MDCTA with negative findings was performed. The raw imaging
      data were reconstructed and the right auricular volume, right atrial volume,
      right auricle height, base long and short axes, base perimeter and area, normal
      angle, and distance were quantitatively measured. RESULTS: Men had significantly
      (P < 0.05) greater values than women in the right auricular volume (13.3 +/- 4.0
      vs. 11.7 +/- 3.7 mL) and height (33.0 +/- 5.0 vs. 30.5 +/- 5.2 mm), the base long
      axis (34.4 +/- 4.1 vs. 33.2 +/- 3.9 mm), area (787.6 +/- 177.6 vs. 771.0 +/-
      143.2 mm2) and perimeter (119.2 +/- 17.5 vs. 115.0 +/- 13.0), and the normal
      distance (22.4 +/- 6.6 vs. 20.2 +/- 6.7 mm). The normal 95 % reference range for
      the right auricular parameters was put forward. The right auricular parameters
      had a good correlation with the right atrium volume, aortic diameter, the body
      weight, height, and body surface area but a bad correlation with the vertebral
      body height. Significantly (P < 0.05) greater values were found in the normal
      angle and distance in subjects below than over 40 years of age. No other
      significant (P > 0.05) difference existed in the other right auricular
      parameters. CONCLUSION: Quantitative measurements of the right auricle can help
      us get a good understanding of the right auricular morphology and its
      relationship with surrounding structures and are helpful for cardiac
      interventions of electrophysiology and radiofrequency ablation.

PMID- 27717983
TI  - ?

PMID- 27717982
TI  - ?

PMID- 27717984
TI  - ?

PMID- 27717987
TI  - ?

PMID- 27717986
TI  - [Smouldering fire].

PMID- 27717985
TI  - Thymoquinone mitigate ischemia-reperfusion-induced liver injury in rats: a
      pivotal role of nitric oxide signaling pathway.
AB  - Oxidative and nitrosative stress-induced endothelial cell damage play an
      essential role in the pathogenesis of hepatic ischemia-reperfusion (IR) injury.
      IR is associated with reduced eNOS expression and exacerbated by superimposed
      stress. NOSTRIN induces intracellular endothelial nitric oxide synthase (eNOS)
      translocation and inducible nitric oxide synthase (iNOS) increases nitric oxide
      (NO) production. Our aim was to assess hepatic expression of iNOS, eNOS, and
      NOSTRIN in IR with or without N-acetylcysteine (NAC) or thymoquinone (TQ)
      pretreatment and to compare their hepatoprotective effects. Surgical induction of
      IR was performed by occlusion of hepatic pedicle for 30 min with mini-clamp and
      reperfused for 30 min. The effects of TQ (20 mg/kg/day) or NAC (300 mg/kg/day)
      administered orally for 10 days were evaluated by serum ALT and AST, oxidative
      stress parameters, NO production, and histopathological analysis. Also,
      localization and expression of iNOS, eNOS, and NOSTRIN were assessed by
      immunofluorescence. TQ or NAC pretreatment significantly decreased elevated serum
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), and
      myeloperoxidase (MPO) activities, malondialdehyde (MDA) level, and NO production.
      In addition, they restored the depleted GSH content and alleviated
      histopathological changes. Furthermore, they up-regulated eNOS and down-regulated
      iNOS and NOSTRIN expressions. TQ exerts its hepatoprotective effect, at least in
      part, by nitric oxide signaling pathway through modulation of iNOS, eNOS, and
      NOSTRIN expressions as well as suppression of oxidative stress.

PMID- 27717988
TI  - MHC class II beta exon 2 variation in pardalotes (Pardalotidae) is shaped by
      selection, recombination and gene conversion.
AB  - The high levels of polymorphism and allelic diversity which characterise genes in
      the major histocompatibility complex (MHC) are thought to be generated and
      maintained through the combined effects of different evolutionary processes.
      Here, we characterised exon 2 of the MHC class II beta genes in two congeneric
      passerine species, the spotted (Pardalotus punctatus) and striated pardalote
      (Pardalotus striatus). We estimated the levels of allelic diversity and tested
      for signatures of recombination, gene conversion and balancing selection to
      determine if these processes have influenced MHC variation in the two species.
      Both species showed high levels of polymorphism and allelic diversity, as well as
      evidence of multiple gene loci and putative pseudogenes based on the presence of
      stop codons. We found higher levels of MHC diversity in the striated pardalote
      than the spotted pardalote, based on the levels of individual heterozygosity,
      sequence divergence and number of polymorphic sites. The observed differences may
      reflect variable selection pressure on the species, resulting from differences in
      patterns of movement among populations. We identified strong signatures of
      historical balancing selection, recombination and gene conversion at the sequence
      level, indicating that MHC variation in the two species has been shaped by a
      combination of processes.

PMID- 27717990
TI  - Reclassification of Brevibacterium halotolerans DSM8802 as Bacillus halotolerans
      comb. nov. Based on Microbial and Biochemical Characterization and Multiple Gene
      Sequence.
AB  - Brevibacterium halotolerans is currently classified as a member of the
      Brevibacterium genus, a genus that groups together many bacterial species of
      similar morphology but diverse biochemical and physiological features. Here we
      suggest, based on multiple gene sequencing and microbial and biochemical
      characterization of two environmental isolates and one type strain (DSM8802),
      that the B. halotolerans DSM8802 (and probably the other deposited under this
      species name) should be re-classified into the Bacillus genus, and offered the
      name B. halotolerans comb. nov.

PMID- 27717989
TI  - Total ankle arthroplasty versus ankle arthrodesis for the treatment of end-stage
      ankle arthritis: a meta-analysis of comparative studies.
AB  - PURPOSE: Total ankle arthroplasty (TAA) and ankle arthrodesis (AA) are the main
      surgical treatment options for end-stage ankle arthritis. Although the
      superiority of each modality remains debated, there remains a lack of high
      quality evidence-based studies, such as randomized controlled clinical trials,
      and meta-analyses of comparative studies. We performed a meta-analysis of
      comparative studies to determine whether there is a significant difference
      between these two procedures in terms of (i) clinical scores and patient
      satisfaction, (ii) re-operations, and (iii) complications. METHODS: We conducted
      a comprehensive search in the MEDLINE, EMBASE, and Cochrane library databases.
      Only retrospective or prospective comparative studies were included in this meta
      analysis. The literature search, data extraction, and quality assessment were
      conducted by two independent reviewers. The primary outcomes were clinical scores
      and patient satisfaction. We also investigated the prevalence of complications
      and the re-operation rate. RESULTS: Ten comparative studies were included (four
      prospective and six retrospective studies). There were no significant differences
      between the two procedures in the American Orthopaedic Foot and Ankle Society
      ankle-hindfoot score, Short Form-36 physical component summary and mental
      component summary scores, visual analogue scale for pain, and patient
      satisfaction rate. The risk of re-operation and major surgical complications were
      significantly increased in the TAA group. CONCLUSIONS: The meta-analysis revealed
      that TAA and AA could achieve similar clinical outcomes, whereas the incidence of
      re-operation and major surgical complication was significantly increased in TAA.
      Further studies of high methodological quality with long-term follow-up are
      required to confirm our conclusions.

PMID- 27717991
TI  - [Bifurcation lesions : How should they be assessed and treated?]
AB  - Bifurcation lesions are a therapeutic challenge in the interventional treatment
      of coronary artery disease. Thus, consideration of anatomical aspects and
      selection of the most appropriate strategy for an individual bifurcation have an
      impact on the interventional outcome. Accordingly, assessment of the type of
      bifurcation stenosis, including the relevance of the side branches, vessel
      diameter and the angle between the two branches are critical for the optimal
      choice of interventional strategy. The fractional flow reserve (FFR) is a
      parameter that provides a measure of the severity of coronary stenosis and
      despite some limitations, FFR can be applied to bifurcation lesions. In addition,
      intravascular imaging tools, such as intravascular ultrasound (IVUS) and optical
      coherence tomography (OCT) can be used to determine anatomical configurations.

PMID- 27717992
TI  - Residential Knowledge of Native Tree Species: A Case Study of Residents in Four
      Southern Ontario Municipalities.
AB  - In the past decade, municipalities across North America have increased investment
      in their urban forests in an effort to maintain and enhance the numerous benefits
      provided by them. Some municipalities have now drafted long-term urban forest
      management plans that emphasize the planting of native trees, to improve
      ecological integrity, and participation of residents, since the majority of urban
      trees are typically located on residential property. Yet it is unclear if
      residents are familiar with native trees or municipalities' urban forest
      management goals. Through a case study of southern Ontario municipalities, we
      administered a survey exploring residents' ability to correctly label common tree
      species as native or non-native, as well as their knowledge of urban forest
      management plans to test four hypotheses: 1) residents in municipalities with an
      urban forest management plans will be more knowledgeable about the native status
      of common street trees; 2) residents who have lived in the area longer will have
      greater knowledge; 3) knowledge level will be correlated with education level,
      ethnicity, and income; and 4) residents' knowledge will be related to having
      planted trees on their property. Our results indicate that residents are better
      able to identify common native trees than correctly determine which trees are non
      native, although knowledge levels are generally low. Knowledge was significantly
      related to length of residency and tree planting experience, supporting
      hypotheses 2 and 4. These results highlight the importance of experience and
      local knowledge acquisition in relation to basic knowledge about urban trees, and
      also point to the failures of resident outreach within the case study
      municipalities.

PMID- 27717993
TI  - Imatinib dose reduction in patients with chronic myeloid leukemia in sustained
      deep molecular response.
AB  - To determine whether a lower imatinib dose could minimize toxicity while
      maintaining the molecular response (MR), imatinib dose was reduced to 300 mg
      daily in 43 patients with chronic myeloid leukemia (CML) in sustained deep
      molecular response to first-line imatinib 400 mg daily. At the time of dose
      reduction, median duration of the deep response was 4.1 (interquartile range
      (IQR) 2.2-5.9) years; molecular response was MR4, MR4.5, and MR5 of the
      international scale in 6, 28, and 9 patients, respectively. Toxicity grade was 1,
      2, and 3 in 28, 8, and 1 patients, respectively; 6 patients underwent dose
      reduction without having side effects. With a median of 1.6 (IQR 0.7-3.2) years
      on imatinib 300 mg daily, only one patient lost the deep molecular response to
      MR3. At the last follow-up, response was MR3, MR4, MR4.5, and MR5 in 1, 3, 9, and
      30 patients, respectively. Toxicity improvement was observed in 23 (62.2 %) of
      the 37 patients with side effects, decreasing to grade 0 in 20 of them. All but
      one anemic patients improved (p = 0.01), the median Hb increase in this subgroup
      of patients being 1 g/dL. In CML patients with sustained deep response to the
      standard imatinib dose, reducing to 300 mg daily significantly improves
      tolerability and preserves efficacy.

PMID- 27717994
TI  - Simultaneous assessment of hand function and neuromuscular quickness through a
      static object manipulation task in healthy adults.
AB  - Both hand function [as seen through the coordination between grip force (GF) and
      load force (LF)] and the ability to produce a submaximal force quickly (i.e.,
      neuromuscular quickness) are two important qualities of motor function that could
      be seriously affected by the presence of neurological diseases. Therefore, their
      quantitative assessment is very important in clinical settings. Within this
      study, we aimed to develop, standardize, and measure the within-session
      reliability of a clinically meaningful test that assesses both hand function and
      neuromuscular quickness simultaneously. Thirteen healthy young adults produced
      around 90 rapid isometric LF pulses to varying submaximal magnitudes by either
      pulling down or pulling up on an externally fixed GF- and LF-measuring device.
      Results revealed high indices of force coordination (i.e., GF scaling as assessed
      by GF/LF and GF coupling as assessed by maximum cross-correlation between GF and
      LF) in both force directions, while GF coupling was higher in downward than in
      upward direction (p < 0.001). Regarding the indices of neuromuscular quickness
      (i.e., the regression parameters obtained from the relationship between peak
      force and it's rate of development and half-relaxation time), results, in
      general, revealed a higher slope (named as rate of force development scaling
      factor; p < 0.01), similar R 2 (p > 0.05), and shorter half-relaxation time (p <
      0.05) for LF than for GF. Furthermore, all of the selected variables showed
      moderate to excellent within-session reliability with only 45 pulses. Findings
      suggest that brief force production tasks should be further evaluated as clinical
      tests of hand function and neuromuscular quickness in various populations.

PMID- 27717995
TI  - Juvenile myelomonocytic leukemia presenting as bilateral breast masses.
AB  - An 8-year-old girl presented with bilateral breast masses and was subsequently
      diagnosed with juvenile myelomonocytic leukemia. Juvenile myelomonocytic leukemia
      is a rare myelodysplastic syndrome that typically presents in boys younger than 3
      years of age with splenomegaly, lymphadenopathy and skin findings. Bilateral
      breast masses in a child are rare and, as such, present a diagnostic dilemma due
      to the relative paucity of cases in the literature. We present a case of
      granulocytic sarcoma of the breasts in a patient with juvenile myelomonocytic
      leukemia. The authors hope that increased reporting and research regarding
      pediatric breast masses will help create awareness for such cases.

PMID- 27717997
TI  - EANM Springer Prizes awarded at EANM' 16 Barcelona.

PMID- 27717996
TI  - A comparison of efficacy of doxazosin 4 and 8 mg in medical expulsive therapy of
      distal ureteral stones: a prospective randomized clinical trial.
AB  - We aimed to investigate the efficacy of two different doses of doxazosin, 4 and 8
      mg, in medical expulsive therapy (MET). This prospective randomized study
      included a total of 66 patients with distal ureteral stones which were radio
      opaque and <=10 mm. All patients were randomly divided into three groups: Group 1
      included 25 patients receiving 4 mg doxazosin. Group 2 included 22 patients
      receiving 8 mg doxazosin. Diclofenac 100 mg p.o. and daily 1500-2000 cc hydration
      were advised to the patients in Groups 1 and 2 to relieve pain. Group 3 consisted
      of 19 patients who were defined as control group and received only hydration and
      analgesics. The mean age of the patients was 30 +/- 7.6, 37.9 +/- 11.5 and 33 +/-
      11.3 in Group 1, Group 2 and Group 3, respectively. The mean stone size was 6.6
      +/- 1.4, 7.1 +/- 1.5 and 6.6 +/- 1.5 in Group 1, Group 2 and Group 3,
      respectively. The stone expulsion rate of the patient groups was 18/25 (72 %),
      15/22 (68.1 %) and 5/19 (25.3 %). There were significantly fewer pain episodes
      and lower analgesic requirement in Groups 1 and 2 (p = 0.021). However, the
      difference between Group 1 and Group 2 was non-significant (p = 0.207). Given the
      data of the present study, doxazosin, an alpha receptor blocker, exhibited equal
      efficacy with 4 or 8 mg doses in MET and was used safely and efficiently in
      ureteral stones <10 mm. The findings of the present study showed that 4 mg dose
      is effective, when doxazosin is preferred for MET.

PMID- 27717998
TI  - Lymphocyte function following radium-223 therapy in patients with metastasized,
      castration-resistant prostate cancer.
AB  - PURPOSE: Therapy with the alpha-emitter radium-223 chloride (223Ra) is an
      innovative therapeutic option in patients with metastasized, castration-resistant
      prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The
      aim of this study was to determine if 223Ra therapy induces an impairment of
      cellular antimicrobial immune responses. METHODS: In 11 patients receiving 223Ra
      treatment, lymphocyte proliferation and the production of pro- and anti
      inflammatory cytokines (interferon-gamma and interleukin-10) were determined,
      using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte
      function after stimulation with mitogens and microbial antigens was assessed
      prior to therapy and at day 1, 7 and 28 after therapy. RESULTS: Lymphocyte
      proliferation and the production of interferon-gamma and interleukin-10 towards
      mitogens and antigens remained unchanged after therapy. Consistent with these in
      vitro data, we did not observe infectious complications after treatment.
      CONCLUSIONS: The results argue against an impairment of lymphocyte function after
      223Ra therapy. Thus, immune responses against pathogens should remain unaffected.

PMID- 27717999
TI  - Effect of bosutinib on the absorption of dabigatran etexilate mesylate, a P
      glycoprotein substrate, in healthy subjects.
AB  - PURPOSE: Bosutinib, a dual Src and Abl tyrosine kinase inhibitor for the
      treatment of chronic myeloid leukemia, demonstrated concentration-dependent
      inhibitory effects on P-glycoprotein (P-gp)-mediated digoxin efflux in vitro,
      suggesting that bosutinib may inhibit P-gp substrates. The effect of bosutinib on
      dabigatran etexilate mesylate (EM) absorption, a P-gp substrate, was evaluated.
      METHODS: In this open-label, randomized, single-dose, one-cohort, two-sequence,
      two-period crossover study, healthy, fed subjects received dabigatran EM (150 mg
      * 1 orally) alone or 1 h after receiving bosutinib tablets (100 mg * 5 orally).
      RESULTS: Dabigatran EM monotherapy and concurrent administration of dabigatran EM
      with bosutinib resulted in similar values for concentration time curves from time
      zero extrapolated to infinity (AUCinf), but slightly lower maximum plasma
      concentration (C max) values (AUCinf, 1182 and 1186 ng.h/mL, respectively; C max,
      129.8 and 114.1 ng/mL). The time to maximum concentration for dabigatran was 2.99
      and 3.99 h for combination therapy. The ratio of the adjusted geometric means
      (test/reference) of dabigatran AUCinf and C max (90 % confidence interval) were
      101.4 % (89.6-114.9 %) and 89.7 % (77.8-103.4 %), respectively, following
      administration of dabigatran EM with bosutinib (test) relative to dabigatran EM
      administered alone (reference). Six subjects receiving combination treatment
      reported a total of seven adverse events (AEs) versus none for subjects receiving
      monotherapy alone. All AEs were mild to moderate and considered treatment
      related. CONCLUSION: These data demonstrate that single doses of bosutinib do not
      affect dabigatran exposure, suggesting that bosutinib is not a clinical inhibitor
      of P-gp. TRIAL REGISTRATION: ClinicalTrials.gov NCT02102633.
      https://clinicaltrials.gov/ct2/show/NCT02102633?term=NCT02102633&rank=1.

PMID- 27718000
TI  - Effect of aprepitant, a moderate CYP3A4 inhibitor, on bosutinib exposure in
      healthy subjects.
AB  - PURPOSE: Bosutinib is an oral, dual Src and Abl tyrosine kinase inhibitor (TKI)
      approved for the treatment of Philadelphia chromosome-positive chronic myeloid
      leukemia resistant or intolerant to prior TKI therapy. Bosutinib is primarily
      metabolized by cytochrome P450 (CYP) 3A4, suggesting drug interaction potential
      with other CYP3A4 modulators. This open-label, randomized, 2-sequence, 2-period
      crossover study assessed the effect of single-dose aprepitant, a moderate CYP3A4
      inhibitor, on the single-dose pharmacokinetic profile of oral bosutinib 500 mg.
      METHODS: Nineteen healthy, fed adults received bosutinib (100 mg * 5) alone or
      coadministered with aprepitant (125 mg * 1) in each treatment period (with a >=14
      day washout); serial blood samples were analyzed. Safety was evaluated. RESULTS:
      Following coadministration of aprepitant with bosutinib, the area under the
      concentration-time curve from time zero extrapolated to infinity (AUCinf) and
      maximum plasma concentration (C max) were higher than in bosutinib alone (AUCinf,
      4719 and 2268 ng*h/mL; C max, 146.0 and 94.94 ng/mL). For bosutinib with
      aprepitant versus bosutinib alone, mean terminal elimination half-life was
      similar (25.99 vs 27.79 h), time to C max was longer (6.02 vs 4.15 h), and
      apparent oral clearance (CL/F) was decreased (105.9 vs 220.4 L/h). The ratio of
      adjusted geometric means of AUCinf and C max for bosutinib with aprepitant
      relative to bosutinib alone were 199 % (90 % confidence interval, 167-237 %) and
      153 % (127-184 %), respectively. Both treatments were well tolerated. CONCLUSION:
      In healthy volunteers, administering a single dose of aprepitant increased the
      AUC and C max following a single dose of bosutinib by 99 and 53 %, respectively.
      These results are consistent with a moderate CYP3A4 inhibitor effect of
      aprepitant on bosutinib (Trial Registration: ClinicalTrials.gov NCT02058277).

PMID- 27718001
TI  - Surgery-Related Muscle Loss and Its Association with Postoperative Complications
      After Major Hepatectomy with Extrahepatic Bile Duct Resection.
AB  - BACKGROUND: Several studies have reported that preoperative sarcopenia negatively
      impacts postoperative outcomes. Meanwhile, changes in skeletal muscle mass during
      the acute phase after surgery and their association with postoperative
      complications are unknown. OBJECTIVE: The objective of this study was to
      investigate the relation between changes in skeletal muscle mass and
      postoperative complications after major hepatectomy with extrahepatic bile duct
      resection. METHODS: This study included 254 patients who underwent major
      hepatectomies with extrahepatic bile duct resections. Total psoas muscle area
      (TPA) was measured using abdominal computed tomography images obtained before and
      1 week after surgery. The percent change in TPA after surgery was calculated.
      Patients were stratified by sex-specific tertiles according to the extent of
      muscle mass change by percentage. Surgery-related muscle loss (SML) was defined
      as the lowest tertile of percent change in TPA. RESULTS: Male patients with a
      percent change of TPA lower than -5.0 % (n = 54) and female patients with that
      lower than -2.6 % (n = 31) were included in the lowest tertile and were
      categorized into a group with SML. The incidence rates of major complications,
      pancreatic fistula, infectious complications, and mortality were all
      significantly higher in the group with SML than in the group without SML. By
      multivariate analyses, SML was identified as an independent factor associated
      with major complications (odds ratio 3.21; 95 % confidential interval 1.82-5.76,
      p < 0.001). CONCLUSIONS: SML is significantly associated with postoperative
      morbidity and mortality in patients who underwent major hepatectomies with
      extrahepatic bile duct resections.

PMID- 27718002
TI  - Sublobar Resection Margin Width Does Not Affect Recurrence of Clinical N0 Non
      small Cell Lung Cancer Presenting as GGO-Predominant Nodule of 3 cm or Less.
AB  - BACKGROUND: Sublobar resection of lung cancer may benefit patients with lung
      cancer presenting as ground-glass opacity (GGO) nodules. The purpose of this
      study was to evaluate the effect of margin width on recurrence after sublobar
      resection in patients with clinical N0 non-small cell lung cancer presenting as
      GGO-predominant nodule. METHODS: We conducted a retrospective chart review of 91
      patients treated for clinical N0 non-small cell lung cancer <=3 cm by sublobar
      resection with clear resection margins. We assigned them to two groups: GGO
      predominant tumor and solid-predominant tumor. Each group was subdivided into two
      groups according to the margin width: resection margin <=5 mm and resection
      margin >5 mm. We analyzed the clinicopathological findings and survival among
      these four groups. RESULTS: There was no recurrence in GGO-predominant tumors
      after sublobar resection. Margin width did not influence the recurrence in GGO
      predominant tumors. In the cases of solid-predominant tumor, 5-year recurrence
      free survival after sublobar resection according to margin width <=5 and >5 mm
      was 24.2 and 79.6 %, respectively (p < 0.001). Therefore, narrow margin width
      (resection margin <=5 mm) was a significant risk factor for recurrence of solid
      predominant tumors (hazard ratio 3.868, 95 % confidence interval 1.177-12.714, p
      = 0.026). CONCLUSIONS: The width between the tumor and resection margin does not
      affect the recurrence after R0 sublobar resection in patients with clinical N0
      GGO-predominant lung cancer <=3 cm. By contrast, margin width is a significant
      risk factor for recurrence after sublobar resection in patients with clinical N0
      solid-predominant lung cancer.

PMID- 27718003
TI  - Multifocal Versus Solitary Papillary Thyroid Carcinoma.

PMID- 27718004
TI  - A Clear Difference Between the Outcomes After a Major Hepatectomy With and
      Without an Extrahepatic Bile Duct Resection.
AB  - BACKGROUND: The procedure of a simple hepatectomy and a hepatectomy with an
      extrahepatic bile duct resection and subsequent choledocho-jejunostomy is largely
      different. However, these two procedures are sometimes included in the same
      category. There are no studies comparing postoperative course and liver
      regeneration rate after a major hepatectomy with and without an extrahepatic bile
      duct resection. METHODS: We retrospectively reviewed medical records of 245
      patients who underwent a right hepatectomy (RH, n = 55) or RH with an
      extrahepatic bile duct resection (RHEBR, n = 190). Postoperative complications,
      including incidence of posthepatectomy liver failure (PHLF) and hepatic
      regeneration rates after surgery, were evaluated. RESULTS: The incidence of PHLF
      was considerably higher in the RHEBR group than in the RH group (39.5 vs. 16.4 %,
      p = 0.001). The percentage of newly regenerated liver volume after the
      hepatectomies on postoperative days 6-8 was significantly lower in the RHEBR
      group than in the RH group (14.0 % in the RH; 7.9 % in the RHEBR group, p <
      0.001). Especially type of surgery (RHEBR) was the only independent risk factor
      for an impaired liver regeneration rate by univariate and multivariate analyses.
      Furthermore, estimated hepatic regeneration rate by stepwise linear regression
      analysis in the RHEBR group was 7.1 % lower (95 % confidence interval 1.8-12.3, p
      = 0.011) than in the RH group. CONCLUSION: These results suggest that the
      procedure of extrahepatic bile duct resection has a possibility of adverse impact
      on the postoperative outcome after major hepatectomy.

PMID- 27718005
TI  - Readmissions After Surgery: A French Nationwide Cross-Sectional Study of
      1,686,602 Procedures Performed in 2010.
AB  - BACKGROUND: Surgical readmissions have been extensively studied in North America,
      but very few data from other countries are available. We aimed to describe
      surgical readmissions in France and to assess their association with hospital
      status, surgical volume, and day surgery activity. METHODS: We performed a cross
      sectional study encompassing all 1270 French hospitals, except for military
      hospitals and hospitals with very small volume. Data were retrieved from the
      national database regarding all patients undergoing surgery between January 1,
      2010 and November 30, 2010. The main outcome measure was 30-day readmission rate.
      Association with hospital status, surgical volume, and the level of day surgery
      were assessed. Risk adjustment was performed based upon administrative
      categories. RESULTS: After exclusion of deaths and hospital transfers, there were
      1,686,602 patients in the study cohort. Thirty-day readmission rate was 5.9 %.
      Distribution was skewed, with 21.5 % of procedures accounting for 33.5 % of all
      30-day readmissions. Early readmissions (<=3 days) were associated with higher
      mortality as compared to those occurring later (>7 days) (3.2 vs. 2.6 %; p <
      0.0001). After multivariate analysis, University hospitals were shown to be
      affected by a significantly greater risk of 30-day readmission as compared to
      private hospitals (odds ratio 1.46 [95 % CI 1.42-1.5]). Other independent factors
      were as follows: male gender, longer initial hospital stay, and comorbidities.
      CONCLUSIONS: Surgical 30-day readmission rate was low, with early readmissions
      being associated with higher mortality. Conversely to prior research, University
      hospitals were shown to be associated with significantly higher risk of 30-day
      readmissions, even after risk adjustment.

PMID- 27718007
TI  - Degradation Processes of Pesticides Used in Potato Cultivations.
AB  - Potato is one of the most important crops, after maize, rice and wheat. Its
      global production is about 300 million tons per year and is constantly
      increasing. It grows in temperate climate and is used as a source of starch,
      food, and in breeding industry.Potato cultivation requires application of
      numerous agro-technical products, including pesticides, since it can be affected
      by insects, weeds, fungi, and viruses. In the European Union the most frequently
      used pesticides in potato cultivations check are: thiamethoxam, lambda
      cyhalothrin and deltamethrin (insecticides), rimsulfuron (herbicide) and
      metalaxyl (fungicide).Application of pesticides improves crop efficiency,
      however, as pesticides are not totally selective, it affects also non-target
      organisms. Moreover, the agrochemicals may accumulate in crops and, as a
      consequence, negatively influence the quality of food products and consumer
      health. Additional risks of plant protection products are related to their
      derivatives, that are created both in the environment (soil, water) and in plant
      organisms, since many of these compounds may exhibit toxic effects.This article
      is devoted to the degradation processes of pesticides used in potato crop
      protection. Attention is also paid to the toxicity of both parent compounds and
      their degradation products for living organisms, including humans. Information
      about the level of pesticide contamination in the environment (water, soil) and
      accumulation level in edible plants complement the current knowledge about the
      risks associated with widespread use of thiamethoxam, lambda-cyhalothrin and
      deltamethrin, rimsulfuron and metalaxyl in potato cultivation.

PMID- 27718008
TI  - Influence of Nanotoxicity on Human Health and Environment: The Alternative
      Strategies.
AB  - Currently, nanotechnology revolutionizing both scientific and industrial
      community due to their applications in the fields of medicine, environmental
      protection, energy, and space exploration. Despite of the evident benefits of
      nanoparticles, there are still open questions about the influence of these
      nanoparticles on human health and environment. This is one of the critical issues
      that have to be addressed in the near future, before massive production of
      nanomaterials. Manufactured nanoparticles, which are finding ever-increasing
      applications in industry and consumer products fall into the category of emerging
      contaminants with ecological and toxicological effects on populations,
      communities and ecosystems. The existing experimental knowledge gave evidence
      that inhaled nanoparticles are less efficiently separated than larger particles
      by the macrophage clearance mechanisms and these nanoparticles are known to
      translocate through the lymphatic, circulatory and nervous systems to many
      tissues and organs, including the brain. In this review we highlight adverse
      impacts of nanoparticles on human and the environment with special emphasis on
      green nanoscience as a sustainable alternative.

PMID- 27718006
TI  - Graft dislocation and graft failure following Descemet membrane endothelial
      keratoplasty (DMEK) using precut tissue: a retrospective cohort study.
AB  - PURPOSE: Although the functional results following DMEK are better than after
      DSAEK, DSAEK still seems to be the standard procedure, as surgeons fear losing
      grafts during DMEK graft preparation. Therefore, eye banks offer precut DMEK
      grafts for direct use by the surgeon. Here, we analysed the functional results
      and complication rates for a precut technique compared to fresh preparations.
      METHODS: We retrospectively compared 453 standard to 11 precut (1-2 days before
      surgery) DMEK cases. Precut preparations did not differ from the standard
      preparation, except that the preparation was stopped after trephination with the
      graft still attached in a small central area. The preparation had to be completed
      before surgery by peeling off the centrally attached part of the graft. This
      technique was first tested in an experimental series of 14 grafts, which were
      unsuitable for transplantation. All surgeries were performed in the same
      standardized way. RESULTS: There was no significant endothelial cell loss during
      the storage period following precut preparation. We found a statistically
      significantly higher endothelial cell loss and graft failure rate for the precut
      grafts. CONCLUSION: Because of the statistically significant higher graft failure
      rate in the precut group, we stopped using this technique, so the numbers in this
      retrospective case series are small. The higher graft failure rate may be
      explained by (ultra)structural changes in the DMEK graft (e.g. accumulation of
      dextran) during the second storage period. Therefore, careful evaluation is
      recommended before using precut DMEK grafts stored in dextran containing media in
      order to avoid early primary graft failures.

PMID- 27718010
TI  - From "ear" to there: a review of biorobotic models of auditory processing in
      lizards.
AB  - The peripheral auditory system of lizards has been extensively studied, because
      of its remarkable directionality. In this paper, we review the research that has
      been performed on this system using a biorobotic approach. The various robotic
      implementations developed to date, both wheeled and legged, of the auditory model
      exhibit strong phonotactic performance for two types of steering mechanisms-a
      simple threshold decision model and Braitenberg sensorimotor cross-couplings. The
      Braitenberg approach removed the need for a decision model, but produced
      relatively inefficient robot trajectories. Introducing various asymmetries in the
      auditory model reduced the efficiency of the robot trajectories, but successful
      phonotaxis was maintained. Relatively loud noise distractors degraded the
      trajectory efficiency and above-threshold noise resulted in unsuccessful
      phonotaxis. Machine learning techniques were applied to successfully compensate
      for asymmetries as well as noise distractors. Such techniques were also
      successfully used to construct a representation of auditory space, which is
      crucial for sound localisation while remaining stationary as opposed to
      phonotaxis-based localisation. The peripheral auditory model was furthermore
      found to adhere to an auditory scaling law governing the variation in frequency
      response with respect to physical ear separation. Overall, the research to date
      paves the way towards investigating the more fundamental topic of auditory metres
      versus auditory maps, and the existing robotic implementations can act as tools
      to compare the two approaches.

PMID- 27718009
TI  - Environmental and occupational exposure to bisphenol A and endometriosis: urinary
      and peritoneal fluid concentration levels.
AB  - OBJECTIVES: The study aimed to give a first data set of bisphenol A (BPA) levels
      in the peritoneal fluid of patients suffering from endometriosis and to
      investigate the relationship between BPA exposure and endometriosis. METHODS: A
      questionnaire investigating the occupational context, life environment, and
      habits was administered to 68 patients suffering from endometriosis and 60
      endometriosis-free subjects (control group). Urine and peritoneal fluids samples
      were collected and analysed by GC/MSMS for BPA dosage. RESULTS: Some of the
      investigated environmental/lifestyle risk factors (closeness to
      industries/activities at risk) were associated with an increase in endometriosis;
      smoking resulted as protective factor; others (use of food plastic boxes) did not
      seem to influence the onset of pathology. The association between the
      occupational exposure summarising all examined risk factors (working activity,
      personal protective equipment, seniority) and endometriosis was statistically
      significant (chi 2 = 5.252, p = 0.02). Contrasting results were obtained when
      specific activities were examined. Detectable urinary BPA levels were found in
      all analysed samples (patients: 1.17-12.68 pg/ul; mean +/- SD, 5.31 +/- 3.36
      pg/ul; control group: 1.28-2.35 pg/ul; mean +/- SD, 1.64 +/- 0.49 pg/ul; median;
      1.46 pg/ul), with a statistically significant difference between patients and
      controls, showing an association between BPA exposure and endometriosis. Only a
      few subjects from the control group supplied peritoneal fluid; hence, no
      comparison test with patients (range 0.39-1.46 pg/ul; mean +/- SD, 0.67 +/- 0.30
      pg/ul; median, 0.58 pg/ul) was carried out. CONCLUSIONS: Results highlight the
      potential association between BPA exposure and endometriosis, as well as the
      current lack of knowledge regarding occupational exposure to BPA and the need of
      epidemiological studies focused on single activities/occupations, such as
      housewives, cleaners, students.

PMID- 27718011
TI  - Gun barrel view of the anterior pelvic ring for percutaneous anterior column or
      superior pubic ramus screw placement.
AB  - BACKGROUND: Traditionally, operative fixation of pelvic and acetabular injuries
      involves complex approaches and significant complications. Accelerated
      rehabilitation, decreased soft tissue stripping and decreased wound complications
      are several benefits driving a recent interest in percutaneous fixation. We
      describe a new fluoroscopic view to guide the placement of screws within the
      anterior pelvic ring. METHODS: Twenty retrograde anterior pelvic ring screws were
      percutaneously placed in ten cadaveric specimens. Arranging a standard C-arm in a
      position similar to obtaining a lateral hip image, with angles of 54 degrees  +/-
      2 degrees  beam to body, 75 degrees  +/- 5 degrees  of reverse cantilever and 14
      degrees  +/- 6 degrees  of outlet, a gun barrel view of the anterior pelvic ring
      is identified. Fluoroscopic images were taken, and the hemipelvi were harvested
      to examine the dimensions of the anterior pelvic ring and inspected for any
      cortical or articular perforation. RESULTS: The minimum cranial-to-caudal
      distance in the anterior pelvic ring was 9 mm (range 6.5-12 mm), and the minimum
      anterior-to-posterior dimension was 9 mm (range 5-15 mm). All but 2 screws were
      completely confined within the osseous corridors. Identifiable on final
      fluoroscopic evaluation, one screw perforated the psoas groove and a second
      perforated the acetabular dome. Overall, 90 % of our screws were accurately and
      safely placed, upon the first attempt, within the anterior pelvic ring using the
      described gun barrel view. CONCLUSION: Employing either open reduction, or
      following a closed or percutaneous reduction, the anterior pelvic ring gun barrel
      view can reproducibly guide safe placement of anterior pelvic ring screw
      fixation. LEVEL OF EVIDENCE: IV.

PMID- 27718012
TI  - In Japanese patients with papillary thyroid carcinoma, TERT promoter mutation is
      associated with poor prognosis, in contrast to BRAF V600E mutation.
AB  - The prognostic value of BRAF V600E and TERT promoter mutation in papillary
      thyroid carcinoma (PTC) is controversial. We examined alterations in BRAF V600E
      and TERT promoter by PCR-direct sequencing in PTC of 144 Japanese patients.
      Alternative lengthening of telomeres was examined as another mechanism of
      telomere maintenance by immunohistochemical staining for ATRX and DAXX. Of the
      clinicopathological characteristics, regional lymph node metastasis, extra
      thyroid extension, multifocality/intrathyroidal spread, and advanced stage
      (III/V) were associated with shorter disease-free survival rate (DFSR). TERT
      promoter mutation was found in eight patients (6 %), and this was significantly
      associated with total thyroidectomy, multifocality/intrathyroidal spread, lymph
      node metastasis and advanced stage. The BRAF V600E mutation was found in 53
      patients (38.2 %) but was not associated with any clinicopathological factors.
      TERT mutations were not correlated with BRAF V600E mutation status. TERT mutation
      positive tumors (TERT+) showed lower DFSR than BRAF V600E -mutation-positive
      tumors (BRAF V600E +), and TERT+/BRAF V600E + tumors showed lower DFSR than BRAF
      V600E + tumors. No cases showed loss of ATRX/DAXX expression by
      immunohistochemistry. TERT promoter mutations showed a lower prevalence in our
      series and appeared to be associated with aggressive behavior. In PTCs,
      telomerase activation by TERT promoter mutation might be more important than
      alternative lengthening of telomeres.

PMID- 27718013
TI  - A single dose of L-DOPA changes perceptual experiences and decreases latent
      inhibition in Parkinson's disease.
AB  - Despite the well-known neuropsychiatric side effects of dopaminergic medications,
      the possible subjective psychotomimetic effects of a single dose of L-DOPA in
      newly diagnosed, drug-naive patients with Parkinson's disease (PD) are not known.
      To investigate this question, we used a visual search task for latent inhibition
      (LI), the Community Assessment of Psychic Experiences (CAPE) scale, and visual
      analog scales for psychotomimetic effects (perception, relaxation, and dysphoria)
      in 28 de novo PD patients before (off) and after (on) the adminstration of L-DOPA
      and in 25 matched healthy control individuals. Results revealed increased LI in
      PD-off and decreased LI in PD-on relative to the control subjects. After the
      administration of L-DOPA, we observed a significant decline in LI in PD. L-DOPA
      also enhanced perceptual experiences (changes in subjective feelings in thinking,
      time perception, and mental "highness"). Greater reduction in LI was associated
      with enhanced perceptual experiences. These results suggest that a single dose of
      L-DOPA has a significant psychotomimetic effect, which is associated with
      decreased LI, a behavioral marker of psychosis-like experiences.

PMID- 27718015
TI  - Steroid-responsive hyperammonemic encephalopathy as first manifestation of
      multiple myeloma.

PMID- 27718014
TI  - Common olfactory ensheathing glial markers in the developing human olfactory
      system.
AB  - The in situ immunocytochemical properties of olfactory ensheathing cells (OECs)
      have been well studied in several small to medium sized animal models including
      rats, mice, guinea pigs, cats and canines. However, we know very little about the
      antigenic characteristics of OECs in situ within the adult and developing human
      olfactory bulb and nerve roots. To address this gap in knowledge we undertook an
      immunocytochemical analysis of the 11-19 pcw human foetal olfactory system. Human
      foetal OECs in situ possessed important differences compared to rodents in the
      expression of key surface markers. P75NTR was not observed in OECs but was
      strongly expressed by human foetal Schwann cells and perineurial olfactory nerve
      fibroblasts surrounding OECs. We define OECs throughout the 11-19 pcw human
      olfactory system as S100/vimentin/SOX10+ with low expression of GFAP. Our results
      suggest that P75NTR is a robust marker that could be utilised with cell sorting
      techniques to generate enriched OEC cultures by first removing P75NTR expressing
      Schwann cells and fibroblasts, and subsequently to isolate OECs after P75NTR
      upregulation in vitro. O4 and PSA-NCAM were not found to be suitable surface
      antigens for OEC purification owing to their ambiguous and heterogeneous
      expression. Our results highlight the importance of corroborating cell markers
      when translating cell therapies from animal models to the clinic.

PMID- 27718016
TI  - Candidate tumor suppressor gene MCPH1 is mutated in colorectal and gastric
      cancers.

PMID- 27718017
TI  - Liver fluke infection and cholangiocarcinoma: a review.
AB  - Parasites are significant groups for carcinogenesis among which liver flukes,
      including Opisthorchis viverrini and Clonorchis sinensis, are typical
      representatives causing cholangiocarcinoma (CCA), the second most common primary
      hepatic malignancy with dismal prognosis. O. viverrini is prevalent in Southeast
      Asia, infecting 10 million people while C. sinensis has a wider distribution in
      East Asia and several Southeast Asian countries, affecting more than 35 million
      people's health. These two worms have some common characteristics and/or
      discrepancies in life cycle, genome, and transcriptome. As hot spots in recent
      years, genome and transcriptome research has extracted numerous novel fluke worm
      derived proteins, which are excellent for carcinogenic exploration. However, just
      a handful of these studies have focused on the metabolic pathway. In this study,
      the main mechanisms of carcinogenesis of both worms, in terms of mechanical
      damage, metabolic products and immunopathology, and other possible pathways, will
      be discussed in detail. This review retrospectively describes the main traits of
      C. sinensis and O. viverrini, their molecular biology and core carcinogenic
      mechanisms in a contrast pattern.

PMID- 27718018
TI  - Clinical, biochemical, and radiological characterization of the calcinosis in a
      cohort of Mexican patients with systemic sclerosis.
AB  - Calcinosis is a frequent complication of systemic sclerosis (SSc) that is usually
      located in extremities but may occur across the board. The aim of our study was
      to identify and quantify the distribution of calcinosis in a cohort of Mexican
      patients with SSc and its association with clinical features and autoantibodies.
      A cohort of patients with SSc (2013 ACR/EULAR criteria), classified in diffuse
      cutaneous (dcSSc) and limited cutaneous (lcSSc) (Le Roy criteria), was studied.
      For their analysis, patients were allocated into those with and without
      calcinosis (clinical and/or radiological). The evaluation included the modified
      Rodnan scale for skin and Medsger disease severity scale (DSS). Calcium,
      phosphorus, vitamin D, and parathyroid hormone (PTH) and antinuclear antibodies
      and extractable nuclear antigens were determined in serum. A total of 109
      patients were included, 41 (37 %) with and 68 (63 %) without calcinosis.
      Calcinosis was more frequent in patients with dcSSc (55 vs 27 %). In total, we
      identified 354 sites with calcinosis and mean per patient of 12.0 +/- 9.1; the
      most common sites affected were the hands (83 %), proximal upper extremity (27
      %), and proximal lower extremity (22 %). Patients with calcinosis had a higher
      score of Rodnan scale, Mesdger DSS, and frequency of anti-nucleolar and anti-Scl
      70 antibodies compared to those without calcinosis. Abnormal PTH elevation was
      found in 35 % of patients with calcinosis and 23 % without it. The prevalence of
      calcinosis is high in Mexican patients with SSc, especially in diffuse variety,
      and is associated with increased severity of disease.

PMID- 27718019
TI  - Mycophenolate mofetil for the patients with interstitial lung diseases in
      amyopathic dermatomyositis with anti-MDA-5 antibodies.

PMID- 27718020
TI  - Prediction of in-hospital mortality and morbidity using high-sensitivity C
      reactive protein after burr hole craniostomy.
AB  - BACKGROUND: The purpose of this study was to assess whether preanesthetic
      laboratory values can predict in-hospital mortality and morbidity in patients who
      have undergone burr hole craniostomy due to chronic subdural hematoma. METHODS:
      From January 2007 to February 2016, the records of 502 consecutive patients who
      underwent burr hole craniotomy were analyzed. All cases of burr hole craniostomy
      were fitted with a drain, as required by our institutional protocol. RESULTS:
      Patients' demographic data and preoperative laboratory values were subjected to
      logistic regression analysis to predict in-hospital mortality and morbidity after
      burr hole craniostomy. Hemoglobin, prothrombin time, activated partial
      thromboplastin time, serum glucose, and high-sensitivity C-reactive protein
      (hsCRP) were found to be significantly associated with in-hospital mortality and
      morbidity by univariate regression analysis, but of these, only hsCRP (hazard
      ratio 1.210, 95 % confidence interval 1.089-1.345, P < 0.001) was found to
      significantly predict in-hospital mortality and morbidity by multivariate
      regression analysis. Areas under the curve for predicting in-hospital mortality
      and morbidity were 0.765 (95 % confidence interval 0.624-0.906, P = 0.002) and
      0.646 (0.559-0.733, P = 0.001), respectively. CONCLUSIONS: Preoperative hsCRP was
      found to be an independent predictor of in-hospital mortality and morbidity after
      burr hole craniostomy due to chronic subdural hematoma.

PMID- 27718021
TI  - Donkin psychosis.
AB  - Donkin psychoses are eclamptic psychoses without seizures. As symptomatic
      psychoses resulting from cerebral endothelial damage, they may explain the lucid
      intervals that sometimes occur between eclampsia and the eruption of psychosis.
      They have the same features as eclamptic psychoses, with onset during pregnancy
      or the early puerperium, especially in first-time mothers, a short duration and
      full recovery in most. The clinical picture is usually delirium, but mania is
      also seen, and some patients have retrograde amnesia or other cognitive defects.
      Donkin psychosis should be considered in the differential diagnosis of
      childbearing psychoses, and collaborative research is needed to clarify their
      differences.

PMID- 27718022
TI  - Erratum to: In vitro cultures of ectodermal monolayers from the model sea anemone
      Nematostella vectensis.

PMID- 27718023
TI  - Expression of caspase 3 in ovarian follicle cells of the lizard Podarcis sicula.
AB  - In this study, our aim was to determine whether caspase 3 plays a role, during
      previtellogenesis, in the ovarian follicular epithelium of the lizard Podarcis
      sicula. We investigated the presence and localization of proform and active
      caspase 3 by enzyme assay, Western blotting and immunocytochemistry. In parallel,
      a fragment of caspase 3 was cloned for the first time in this species, sequenced
      and used for in situ hybridization to localize messengers and analysed by a
      phylogenetic survey to shed light on its homology with reptilian caspases.
      Results demonstrated that: (1) the follicle cells expressed a caspase of the 3/7
      group and the mRNA for caspase 3 was transcribed in the stem phase and was
      completely translated during cell differentiation; (2) the proform protein was
      stored during the differentiated (nurse) stage and activated at the end of
      previtellogenesis provoking the degeneration of cells; (3) the predicted protein
      sequence, although partial, had a strong similarity with the known reptilian
      caspases 3. The epithelial cells of the ovarian follicle, therefore, do not
      employ caspase 3 during the nurse stage but, instead, prepare for apoptosis long
      before the process actually begins. The relevance of this strategy is discussed.

PMID- 27718024
TI  - Chronic administration of methionine and/or methionine sulfoxide alters oxidative
      stress parameters and ALA-D activity in liver and kidney of young rats.
AB  - High levels of methionine (Met) and methionine sulfoxide (MetO) are found in
      several genetic abnormalities. Oxidative stress is involved in the
      pathophysiology of many inborn errors of metabolism. However, little is known
      about the role of oxidative damage in hepatic and renal changes in
      hypermethioninemia. We investigated the effect of chronic treatment with Met
      and/or MetO on oxidative stress parameters in liver and kidney, as lipid
      peroxidation (TBARS), total sulfhydryl content (SH), reactive oxygen species
      (ROS) and enzymes activities superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx) and delta aminolevulinic dehydratase (ALA-D). Serum
      biochemical parameters were evaluated. Wistar rats were treated daily with two
      subcutaneous injections of saline (control), Met (0.2-0.4 g/kg), MetO (0.05-0.1
      g/kg) and the association between these (Met plus MetO) from the 6th to the 28th
      day of life. Our data demonstrated an increase of glucose and urea levels in all
      experimental groups. Cholesterol (MetO and Met plus MetO) were decreased and
      triglycerides (MetO) were increased. SOD (MetO and Met plus MetO) and CAT (Met,
      MetO and Met plus MetO) activities were decreased, while GPx was enhanced by MetO
      and Met plus MetO treatment in liver. In kidney, we observed a reduction of SH
      levels, SOD and CAT activities and an increase of TBARS levels in all
      experimental groups. ROS levels in kidney were increased in MetO and Met plus
      MetO groups. ALA-D activity was enhanced in liver (MetO and Met plus MetO) and
      kidney (Met plus MetO). These findings help to understand the pathophysiology of
      hepatic and renal alterations present in hypermethioninemia.

PMID- 27718025
TI  - In vivo imaging of a cone mosaic in a patient with achromatopsia associated with
      a GNAT2 variant.
AB  - PURPOSE: The 2 most common causative genes for achromatopsia (ACHM) are CNGA3 and
      CNGB3; other genes including GNAT2 account for only a small portion of ACHM
      cases. The cone mosaics in eyes with CNGA3 and CNGB3 variants are severely
      disrupted; the cone mosaics in patients with GNAT2-associated ACHM; however, have
      been reported to show a contiguous pattern in adaptive optics (AO) retinal
      images. The purpose of this study was to analyze the cone mosaic of another case
      of GNAT2-associated ACHM. PATIENT AND METHODS: The patient was a 17-year-old
      Japanese boy. Comprehensive ocular examinations including fundus photography,
      electroretinography (ERGs), optical coherence tomography (OCT), and whole-exome
      analysis were performed. The cone mosaic was recorded with a flood-illuminated AO
      fundus camera, and the cone density was compared with those of 10 normal control
      eyes. RESULTS: The patient had the typical phenotype of ACHM, and a novel
      homozygous variant, c.730_743del, in GNAT2 was identified. The fundus did not
      show any specific abnormalities, and the OCT images showed the presence of the
      ellipsoid zone. The AO fundus image showed a clearly defined cone mosaic around
      the fovea. The cone density at 500 MUm from the fovea was reduced by 15-30 % as
      compared with those of the normal eyes. CONCLUSIONS: This is the first
      description of a Japanese patient with ACHM with a novel GNAT2 variant. The eyes
      of this patient had a preserved cone structure with loss of function.

PMID- 27718026
TI  - Effect of vitreomacular separation on macular thickness determined by spectral
      domain optical coherence tomography.
AB  - PURPOSE: To determine the effects of vitreomacular separation on macular
      thickness. METHODS: This was a retrospective, observational, cross-sectional
      study. Average foveal and central minimum thicknesses were measured by spectral
      domain optical coherence tomography (SD-OCT) in 308 eyes of 308 healthy subjects
      (healthy group) and 298 normal fellow eyes of 298 patients with a unilateral
      macular hole (MH group). Multiple regression analyses were performed to determine
      the effects of various factors on the macular thickness. RESULTS: The mean age of
      the healthy group was 67.3 +/- 9.6 years (range 40-88 years) and that of the MH
      group was 67.8 +/- 7.0 years (range 43-91). SD-OCT images showed that 149 eyes
      (48.4 %) in the healthy group and 174 eyes (58.4 %) in the MH group had a
      vitreomacular separation. In the healthy group, the central minimum thickness of
      eyes with a vitreomacular separation (196 um) was significantly thinner than
      those without a vitreomacular separation (205 um; P < 0.001). In the MH group,
      the average foveal thickness (234 um) and the central minimum thickness (177 um)
      in eyes with a vitreomacular separation were thinner than those without it (247
      and 199 um, respectively; both P < 0.001). Multiple regression analyses showed
      that a vitreomacular separation was significantly correlated with thinner central
      minimum thicknesses in both groups (P < 0.001) and also with the average foveal
      thickness in the MH group (P < 0.001). CONCLUSIONS: A vitreomacular separation
      caused thinning of the central fovea in both the healthy eyes and the normal
      fellow eyes of unilateral MH patients; the extent of foveal thinning is greater
      in the MH group.

PMID- 27718027
TI  - Safety and efficacy of treatment strategies for posterior inferior cerebellar
      artery aneurysms: a systematic review and meta-analysis.
AB  - INTRODUCTION: We conducted a systematic review of the literature to evaluate the
      safety and efficacy of treatment strategies for PICA aneurysms. METHODS: A
      systematic search of Medline, EMBASE, Scopus, and Web of Science was done for
      studies published through November 2015. We included studies that described
      treatment of PICA aneurysms with >=10 patients. Random-effects meta-analysis was
      used to pool the following outcomes: complete occlusion, technical success,
      periprocedural morbidity/mortality, stroke rates, aneurysm recurrence/rebleed, CN
      palsies rates, and long-term neurological morbidity/mortality. RESULTS: We
      included 29 studies with 796 PICA aneurysms. When considering all ruptured PICA
      aneurysms, complete occlusion rates were 97.1 % (95 % CI = 94.5-99.0 %) in the
      surgical group and 84.3 % (95 % CI = 73.8-92.6 %) in the endovascular group.
      Aneurysm recurrence occurred in 1.4 % (95 % CI = 0.3-3.3 %) after surgery and in
      6.9 % (95 % CI = 3.6-10.9 %) after endovascular treatment. Overall neurological
      morbidity and mortality were 14.4 % (95 % CI = 8.7-21.2 %) and 9.8 % (95 % CI =
      5.8-14.8 %) after surgery and 15.1 % (95 % CI = 10.5-20.2 %) and 17.1 % (95 % CI
      = 11.5-23.7 %) after endovascular treatment, respectively. When considering all
      unruptured PICA aneurysms, complete occlusion rates were 92.9 % (95 % CI = 79.5
      100 %) in the surgical group and 75.7 % (95 % CI = 45.4-97.1 %) in the
      endovascular group. Overall long-term good neurological outcome rates were 91.5 %
      (95 % CI = 74.4-100 %) in the surgical series and 93.3 % (95 % CI = 82.7-99.5 %)
      in the endovascular group. CONCLUSIONS: Our meta-analysis demonstrated that both
      treatment modalities are technically feasible with high rates of technical
      success and effective with sufficient long-term aneurysm occlusion rates. Our
      data suggest that surgery is associated with superior angiographic outcomes.
      While endovascular therapy could be a reasonable first-line treatment option for
      proximal PICA aneurysms, surgery remains a highly effective first-line choice for
      distal PICA aneurysms. These findings should be considered when deciding the best
      therapeutic strategy.

PMID- 27718028
TI  - Measuring experimental cyclohexane-water distribution coefficients for the SAMPL5
      challenge.
AB  - Small molecule distribution coefficients between immiscible nonaqueuous and
      aqueous phases-such as cyclohexane and water-measure the degree to which small
      molecules prefer one phase over another at a given pH. As distribution
      coefficients capture both thermodynamic effects (the free energy of transfer
      between phases) and chemical effects (protonation state and tautomer effects in
      aqueous solution), they provide an exacting test of the thermodynamic and
      chemical accuracy of physical models without the long correlation times inherent
      to the prediction of more complex properties of relevance to drug discovery, such
      as protein-ligand binding affinities. For the SAMPL5 challenge, we carried out a
      blind prediction exercise in which participants were tasked with the prediction
      of distribution coefficients to assess its potential as a new route for the
      evaluation and systematic improvement of predictive physical models. These
      measurements are typically performed for octanol-water, but we opted to utilize
      cyclohexane for the nonpolar phase. Cyclohexane was suggested to avoid issues
      with the high water content and persistent heterogeneous structure of water
      saturated octanol phases, since it has greatly reduced water content and a
      homogeneous liquid structure. Using a modified shake-flask LC-MS/MS protocol, we
      collected cyclohexane/water distribution coefficients for a set of 53 druglike
      compounds at pH 7.4. These measurements were used as the basis for the SAMPL5
      Distribution Coefficient Challenge, where 18 research groups predicted these
      measurements before the experimental values reported here were released. In this
      work, we describe the experimental protocol we utilized for measurement of
      cyclohexane-water distribution coefficients, report the measured data, propose a
      new bootstrap-based data analysis procedure to incorporate multiple sources of
      experimental error, and provide insights to help guide future iterations of this
      valuable exercise in predictive modeling.

PMID- 27718029
TI  - Predicting binding poses and affinities for protein - ligand complexes in the
      2015 D3R Grand Challenge using a physical model with a statistical parameter
      estimation.
AB  - The 2015 D3R Grand Challenge provided an opportunity to test our new model for
      the binding free energy of small molecules, as well as to assess our protocol to
      predict binding poses for protein-ligand complexes. Our pose predictions were
      ranked 3-9 for the HSP90 dataset, depending on the assessment metric. For the
      MAP4K dataset the ranks are very dispersed and equal to 2-35, depending on the
      assessment metric, which does not provide any insight into the accuracy of the
      method. The main success of our pose prediction protocol was the re-scoring stage
      using the recently developed Convex-PL potential. We make a thorough analysis of
      our docking predictions made with AutoDock Vina and discuss the effect of the
      choice of rigid receptor templates, the number of flexible residues in the
      binding pocket, the binding pocket size, and the benefits of re-scoring. However,
      the main challenge was to predict experimentally determined binding affinities
      for two blind test sets. Our affinity prediction model consisted of two terms, a
      pairwise-additive enthalpy, and a non pairwise-additive entropy. We trained the
      free parameters of the model with a regularized regression using affinity and
      structural data from the PDBBind database. Our model performed very well on the
      training set, however, failed on the two test sets. We explain the drawback and
      pitfalls of our model, in particular in terms of relative coverage of the test
      set by the training set and missed dynamical properties from crystal structures,
      and discuss different routes to improve it.

PMID- 27718030
TI  - Beyond the Cut Hunter: A Historical Epidemiology of HIV Beginnings in Central
      Africa.
AB  - In the absence of direct evidence, an imagined "cut hunter" stands in for the
      index patient of pandemic HIV/AIDS. During the early years of colonial rule, this
      explanation goes, a hunter was cut or injured from hunting or butchering a
      chimpanzee infected with simian immunodeficiency virus, resulting in the first
      sustained human infection with the virus that would emerge as HIV-1M. We argue
      here that the "cut hunter" relies on a historical misunderstanding and ecological
      oversimplification of human-chimpanzee (Pan Troglodytes troglodytes) interactions
      that facilitated pathogenic transmission. This initial host shift cannot explain
      the beginnings of the HIV/AIDS pandemic. Instead, we must understand the
      processes by which the virus became transmissible, possibly between Sangha basin
      inhabitants and ultimately reached Kinshasa. A historical epidemiology of the
      late nineteenth and twentieth centuries, provides a much-needed corrective to the
      major shortcomings of the cut hunter. Based on 62 oral historical interviews
      conducted in southeastern Cameroon and archival research, we show that HIV
      emerged from ecological, economic, and socio-political transformations of the
      late nineteenth and twentieth centuries. The gradual imposition of colonial rule
      built on and reoriented ecologies and economies, and altered older patterns of
      mobility and sociality. Certain changes may have contributed to the initial viral
      host shift, but more importantly, facilitated the adaptation of HIV-1M to human
      to-human transmission. Our evidence suggests that the most critical changes
      occurred after 1920. This argument has important implications for public health
      policy, underscoring recent work emphasizing alternative pathways for zoonotic
      spillovers into human beings.

PMID- 27718031
TI  - Influence of Antithrombin on the Regimes of Blood Coagulation: Insights from the
      Mathematical Model.
AB  - Blood coagulation is regulated through a complex network of biochemical reactions
      of blood factors. The main acting enzyme is thrombin whose propagation in blood
      plasma leads to fibrin clot formation. Spontaneous clot formation is normally
      controlled through the action of different plasma inhibitors, in particular,
      through the thrombin binding by antithrombin. In the current study we develop a
      mathematical model of clot formation both in quiescent plasma and in blood flow
      and determine the analytical conditions on the antithrombin concentration
      corresponding to different regimes of blood coagulation.

PMID- 27718032
TI  - Early Postoperative Intraperitoneal Chemotherapy for Low-Grade Appendiceal
      Mucinous Neoplasms with Pseudomyxoma Peritonei: Is it Beneficial?
AB  - BACKGROUND: There is little evidence for the use of early postoperative
      intraperitoneal chemotherapy (EPIC) in patients with low-grade appendiceal
      mucinous neoplasms (LAMNs) with pseudomyxoma peritonei (PMP). This study aims to
      assess the outcomes regarding the use of EPIC in a large cohort of patients with
      LAMNs with PMP uniformly treated by cytoreductive surgery (CRS) and perioperative
      intraperitoneal chemotherapy (PIC), all of whom received hyperthermic
      intraperitoneal chemotherapy (HIPEC), and most of whom also received EPIC.
      METHODS: This was a retrospective study of prospectively collected data of
      consecutive patients with peritoneal carcinomatosis of appendiceal origin who
      underwent CRS and PIC by one surgical team at St George Hospital in Sydney,
      Australia, between January 1996 and November 2015. Subgroup analyses were
      performed for patients with a high Peritoneal Cancer Index (PCI) >20 and also
      based on histopathological subtypes of LAMNs. RESULTS: A total of 250 patients
      formed the cohort of this study. No significant differences were observed in
      terms of hospital mortality (p = 0.153), major morbidity rate (i.e., grade
      III/IV; p = 0.593), intensive care unit stay (p = 0.764), and total hospital stay
      (p = 0.927); however, patients who received HIPEC + EPIC had a significantly
      longer stay in the high dependency unit. Multivariate analysis showed combined
      HIPEC with EPIC is an independent prognostic factor for better survival outcomes
      (hazard ratio 0.30, 95 % confidence interval 0.12-0.74; p = 0.009), adjusted for
      age, PCI, and histopathological subtypes. CONCLUSIONS: The combination of HIPEC +
      EPIC can provide additional survival benefits for patients with LAMNs with PMP
      compared with HIPEC alone, without increasing postoperative morbidity and
      mortality. EPIC should be considered following CRS and HIPEC for patients with
      LAMNs with PMP.

PMID- 27718033
TI  - Surgeon Volume, Patient Age, and Tumor-Related Factors Influence the Need for Re
      Excision After Breast-Conserving Surgery.
AB  - BACKGROUND: Breast-conserving surgery (BCS) is the preferred surgical approach
      for the majority of patients with early-stage breast cancer. There are frequent
      issues regarding pathologic margin status, requiring margin re-excision, and, in
      the literature, there is significant variability in re-excision rates, suggesting
      this is a potential quality-of-care issue. Understanding the patient-, disease-,
      and physician-related factors influencing reoperation rates is of importance in
      an effort to minimize this occurrence. METHODS: A retrospective analysis of all
      patients referred to our cancer center over a 3-year period (1 January 2011-31
      December 2013) was performed. Surgeon volume, and patient- and tumor-related
      factors were assessed for their impact on re-excision rates. Multivariate
      logistic regression analysis was performed to identify variables of significance
      influencing reoperation rates after attempted BCS. RESULTS: Overall, 594 patients
      underwent initial BCS, with 159 (26.8%) patients requiring at least one re
      excision to ensure negative pathologic margins. On multivariate analysis, low
      surgeon case volume, patient age (under 46 years of age), tumor size (>2 cm), and
      lobular carcinoma were associated with an increased re-excision rate. CONCLUSION:
      Re-excisions are frequent after BCS and are influenced by surgeon volume, patient
      age, and tumor-related factors. These factors should be considered when
      counseling patients considering BCS, and also for quality assurance.

PMID- 27718034
TI  - Consequences of Violent Victimization for Native American Youth in Early
      Adulthood.
AB  - Native American youth are at an elevated risk of violent victimization. And
      because of their vulnerable position in society, they may also be at risk of
      experiencing a host of adverse consequences as a result of being victimized.
      Accordingly, using a subsample of 558 Native American youth and two waves of data
      from the National Longitudinal Study of Adolescent to Adult Health (49.8 %
      female; 12-19 years at Wave I; 19-26 years at Wave III), we examined the effects
      of violent victimization during adolescence on a range of outcomes in early
      adulthood (poor health, depressive symptoms, suicidality, financial hardship,
      violent and property offending, alcohol problems, hard drug use, and marijuana
      use). We also assessed whether youth's attachments to family and to school
      moderate the effects of victimization on these outcomes. The results showed that
      adolescent victimization is linked to a small number of outcomes-poor health,
      depressive symptoms, and violent offending-and that the protective effects of
      social attachments are not widespread. Specifically, family attachments moderated
      the effects of victimization on poor health and depressive symptoms, and school
      attachments moderated the effects of victimization on property offending. These
      findings suggest that the consequences of victimization and the protective
      effects of social attachments may differ for Native American youth, and that
      further quantitative and qualitative research is necessary to understand these
      patterns.

PMID- 27718035
TI  - GART mediates the renewal of intestinal epithelial barrier via p38/p53/PUMA
      cascade in colitis.
AB  - Glycinamide ribonucleotide formyltransferase (GART) has been established as a
      pivotal enzyme in de novo purine synthesis, and mediates cellular apoptosis in
      many diseases. We aimed to investigate the role of GART in the pathogenesis of
      Crohn's disease (CD). In our study, we demonstrated for the first time that GART
      expression is up-regulated in patients with active CD and in 2,4,6
      trinitrobenzene sulfonic acid (TNBS)-induced acute colitis model. Moreover, the
      inhibition of GART induced cellular apoptosis and suppressed the migration of
      IECs through the activation of the MEKK3-MKK3-p38 mitogen-activated protein
      kinase (MAPK) pathway, following with the dys-regulation of p53 and p53 up
      regulated modulator of apoptosis (PUMA). Taken together, GART plays a critical
      role in the protection of cellular apoptosis and migration of intestinal
      epithelial cells to maintain the integrity of the epithelial barrier, thus
      providing a new potential approach in designing a novel therapy for CD.

PMID- 27718036
TI  - "I Am Becoming More and More Like My Eldest Brother!": The Relationship Between
      Older Siblings, Adolescent Gambling Severity, and the Attenuating Role of Parents
      in a Large-Scale Nationally Representative Survey Study.
AB  - The present study examined the association between having older siblings who
      gamble and adolescent at-risk/problem gambling and how parents (i.e., parental
      knowledge of their whereabouts) and peers might moderate such effects. Data were
      drawn from the ESPAD(r)Italia2012 survey (European School Survey Project on
      Alcohol and Other Drugs) comprising a nationally representative Italian sample of
      adolescents. The analysis was carried out on a subsample of 10,063 Italian
      students aged 15-19 years (average age = 17.10; 55 % girls) who had at least one
      older sibling and who had gambled at some point in their lives. Respondents'
      problem gambling severity, older gambler sibling, gambler peers, parental
      knowledge, and socio-demographic characteristics were individually assessed.
      Multinomial logistic regression analyses including two- and three-way
      interactions were conducted. The odds of being an at-risk/problem gambler were
      higher among high school students with older siblings that gambled and those with
      peers who gambled. Higher parental knowledge (of who the adolescent was with and
      where they were in their leisure time) was associated with lower rates of at
      risk/problem gambling. There was also an interaction between gamblers with older
      siblings and parental knowledge. The combination of having siblings who gambled
      and a greater level of parental knowledge was associated with lower levels of
      problem gambling. The present study confirmed the occurrence of social risk
      processes (older siblings and peers who gambled) and demonstrated that gambling
      among older siblings and peers represents an important contextual factor for
      increased at-risk/problem gambling. However, parental knowledge appears to be
      sufficient to counterbalance the influence of older siblings.

PMID- 27718038
TI  - Evaluating the role of phase I expansion cohorts in oncologic drug development.
AB  - Importance Use of expansion cohorts (EC) in phase I trials is increasing.
      However, the utility of phase I EC in aiding drug development is unclear. We
      sought to determine factors associated with the inclusion of EC in phase I
      studies and the impact of EC on subsequent clinical development. Methods We
      performed a systematic review of all phase I trials published in the Journal of
      Clinical Oncology between June 2004 and May 2014. Presence of an EC, number of
      participants, funding source, class of agent, tumor type, and maximum tolerated
      dose (MTD)/recommended phase 2 dose (RP2D) were identified. Subsequent conduct of
      phase II studies and FDA approval of the study agent was also assessed. Results
      We identified 252 phase I studies. An EC was included in 105 studies. Average
      accrual on EC studies was 47 compared to 31 in studies without EC (p < 0.0001).
      There was no impact of time on the inclusion of EC. Only 4 % of phase I studies
      with an EC provided sample size justification. Source of funding had the only
      significant association with inclusion of EC. Addition of a phase I EC did not
      impact the phase I MTD/RP2D, subsequent phase II trial, or FDA approval.
      Conclusion The importance of including an EC in phase I trials is subject to
      ongoing debate. Our results demonstrated little benefit to including EC in phase
      I studies. These findings support that innovative design strategies are needed to
      optimize the utility of EC in phase I studies.

PMID- 27718037
TI  - Finite-Element Modelling of the Acoustic Input Admittance of the Newborn Ear
      Canal and Middle Ear.
AB  - Admittance measurement is a promising tool for evaluating the status of the
      middle ear in newborns. However, the newborn ear is anatomically very different
      from the adult one, and the acoustic input admittance is different than in
      adults. To aid in understanding the differences, a finite-element model of the
      newborn ear canal and middle ear was developed and its behaviour was studied for
      frequencies up to 2000 Hz. Material properties were taken from previous
      measurements and estimates. The simulation results were within the range of
      clinical admittance measurements made in newborns. Sensitivity analyses of the
      material properties show that in the canal model, the maximum admittance and the
      frequency at which that maximum admittance occurs are affected mainly by the
      stiffness parameter; in the middle-ear model, the damping is as important as the
      stiffness in influencing the maximum admittance magnitude but its effect on the
      corresponding frequency is negligible. Scaling up the geometries increases the
      admittance magnitude and shifts the resonances to lower frequencies. The results
      suggest that admittance measurements can provide more information about the
      condition of the middle ear when made at multiple frequencies around its
      resonance.

PMID- 27718039
TI  - 4-methylumbelliferone and imatinib combination enhances senescence induction in
      chronic myeloid leukemia cell lines.
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative syndrome characterized by
      the presence of the Philadelphia chromosome which encodes a constitutively
      activated tyrosine kinase (BCR-ABL). The first line treatment for CML consists on
      BCR-ABL inhibitors such as Imatinib. Nevertheless, such treatment may lead to the
      selection of resistant cells. Therefore, it is of great value to find molecules
      that enhance the anti-proliferative effect of first-line drugs. Hyaluronan is the
      main glycosaminglican of the extracellular matrix which is involved in tumor
      progression and multidrug resistance. We have previously demonstrated that the
      inhibition of hyaluronan synthesis by 4-methylumbelliferone (4MU) induces
      senescence and can revert Vincristine resistance in CML cell lines. However, the
      effect of 4MU on Imatinib therapy remains unknown. The aim of this work was to
      determine whether the combination of 4MU with Imatinib is able to modulate the
      proliferation as well as apoptosis and senescence induction in human CML cell
      lines. For this purpose the ATCC cell line K562, and its multidrug resistant
      derivate, Kv562 were used. Cells were exposed to 4MU, Imatinib or a combination
      of both. We demonstrated that 4MU and Imatinib co-treatment abrogated the
      proliferation of both cell lines. However, such co-treatment did not increase the
      levels of apoptosis when compared with the treatment with Imatinib alone. For
      both cell lines the mechanisms of tumor suppression involved was senescence,
      since the combination of 4MU and Imatinib arrested the cell cycle and increased
      senescence associated beta-galactosidase activity and senescence associated
      heterochromatin foci presence when compared to each drug alone. Moreover, 4MU,
      Imatinib and 4MU + Imatinib decreased pAkt/Akt ratio in both cell lines and
      reduced the pERK/ERK ratio only in K562 cells. These findings highlight the
      potential use of 4MU together with Imatinib for CML therapy.

PMID- 27718040
TI  - Biogas properties and enzymatic analysis during anaerobic fermentation of
      Phragmites australis straw and cow dung: influence of nickel chloride supplement.
AB  - The importance of nickel (added as NiCl2) on mesophilic anaerobic fermentation of
      Phragmites australis straw and cow dung was demonstrated by investigating the
      biogas properties, pH values, organic matter degradation [chemical oxygen demand
      (COD)] and enzyme activities (cellulase, protease and dehydrogenase) during the
      fermentation process. The results showed that Ni2+ addition increased the
      cumulative biogas yields by >18 % by improving the efficiency of first peak stage
      and bringing forward the second peak stage. The pH values were not significantly
      influenced by Ni2+ addition (p > 0.05). Biogas yields were associated with
      variations in COD concentrations rather than momentary concentrations. At the
      start-up stage of fermentation (4th day), the biogas yields increased gradually
      together with the increase of dehydrogenase activities at elevated Ni2+
      concentrations when cellulase and protease activities were similar in all test
      groups. It is suggested that Ni2+ addition was mainly dependent on the
      methanogenic stage. After the start-up stage, the impact of Ni2+ addition on
      biogas production was mainly dependent on its effect on cellulase activities,
      rather than protease or dehydrogenase activities.

PMID- 27718042
TI  - Genetic diversity and vector transmission of phytoplasmas associated with sesame
      phyllody in Iran.
AB  - During 2010-14 surveys in the major sesame growing areas of Fars, Yazd and
      Isfahan provinces (Iran), genetic diversity and vector transmission of
      phytoplasmas associated with sesame phyllody were studied. Virtual RFLP,
      phylogenetic, and DNA homology analyses of partial 16S ribosomal sequences of
      phytoplasma strains associated with symptomatic plants revealed the presence of
      phytoplasmas referable to three ribosomal subgroups, 16SrII-D, 16SrVI-A, and
      16SrIX-C. The same analyses using 16S rDNA sequences from sesame phyllody
      associated phytoplasmas retrieved from GenBank database showed the presence of
      phytoplasmas clustering with strains in the same subgroups in other Iranian
      provinces including Bushehr and Khorasan Razavi. Circulifer haematoceps and
      Orosius albicinctus, known vectors of the disease in Iran, were tested for
      transmission of the strains identified in this study. C. haematoceps transmitted
      16SrII-D, 16SrVI-A, and 16SrIX-C phytoplasmas, while O. albicinctus only
      transmitted 16SrII-D strains. Based on the results of the present study and
      considering the reported presence of phytoplasmas belonging to the same ribosomal
      subgroups in other crops, sesame fields probably play an important role in the
      epidemiology of other diseases associated with these phytoplasmas in Iran.

PMID- 27718041
TI  - ITS2 secondary structure for species circumscription: case study in southern
      African Strychnos L. (Loganiaceae).
AB  - Recently developed computational tools in ITS2 sequence-structure phylogenetics
      are improving tree robustness by exploitation of the added information content of
      the secondary structure. Despite this strength, however, their adoption for
      species-level clarifications in angiosperms has been slow. We investigate the
      utility of combining ITS2 sequence and secondary structure to separate species of
      southern African Strychnos, and assess correlation between compensatory base
      changes (CBCs) and currently recognised species boundaries. Combined phylogenetic
      analysis of sequence and secondary structure datasets performed better, in terms
      of robustness and species resolution, than analysis involving primary sequences
      only, achieving 100 and 88.2 % taxa discriminations respectively. Further, the
      Strychnos madagascariensis complex is well-resolved by sequence-structure
      phylogenetic analysis. The 17 Strychnos species corresponded to 14 ITS2 CBC
      clades. Four of the five taxa in section Densiflorae belong to a single CBC
      clade, whose members tend to form natural hybrids. Our finding supports the
      application of ITS2 as a complementary barcoding marker for species
      identification. It also highlights the potential of comparative studies of ITS2
      CBC features among prospective parental pairs in breeding experiments as a rapid
      proxy for cross compatibility assessment. This could save valuable time in crop
      improvement. Patterns of CBC evolution and species boundaries in Strychnos
      suggests a positive correlation. We conclude that the CBC pattern coupled with
      observed ITS2 sequence paraphyly in section Densiflorae points to a speciation
      work-in-progress.

PMID- 27718044
TI  - The osteoclasts attach to the bone surface where the extracellular calcium
      concentration decreases.
AB  - Osteoclasts demineralize and resorb bone once they attach to its surface.
      However, it's still unclear how the osteoclasts choose the specific sites for
      their attachments. It is postulated in this article that the decreased
      extracellular free ionized calcium concentration (Ca2+[e]) can provide a
      microenvironment for osteoclasts to recognize and then initiate the attachment
      process. The osteoclasts initially attach to the bone surface via integrating its
      integrin alphavbeta3 and RGD containing ligands in bone matrix. Through the
      interaction with RGD-containing ligand, the integrin alphavbeta3 forms
      carboxylate oxygen noncovalent, which is further stabilized by accompanied
      electrostatic interaction between the Ca2+ and the beta3 subunit. There are two
      types of cation-binding sites on the beta3 subunit: the high affinity Ca2+
      binding site ("LC" site) that activates the osteoclasts by promoting the
      combination; the low affinity Ca2+ binding site ("I" site, also named ADMIDAS)
      that deactivates the osteoclasts by dissociating the combination and it can
      override the "LC" site's positive effect on osteoclasts when necessary. Normally
      the Ca2+ concentration of bone extracellular fluid is maintained within a normal
      range by osteocytes, keeping the "I" sites activated. When the osteocytes'
      function stalls and the ambient Ca2+ concentration falls below the affinity
      discrimination threshold between the "I" site and the "LC" site, the "LC" site's
      promoting function starts to out compete the "I" site in its inhibitory effect,
      in which case the inactive integrin alphavbeta3 turns into an extended active
      form and the osteoclasts start to attach, signifying the initiation of bone
      resorption.

PMID- 27718045
TI  - Increased Expression of Caspase-12 After Experimental Subarachnoid Hemorrhage.
AB  - Convincing evidences have proved that apoptosis plays a vital role in the
      pathogenesis of early and delayed brain injury following subarachnoid hemorrhage
      (SAH). Recently, a novel caspase-12-mediated apoptotic pathway has been reported
      to be induced by excess endoplasmic reticulum (ER) stress. Extensive protein
      damage occurs after SAH, which may trigger ER stress-associated apoptotic
      pathway. Thus, we hypothesized that caspase-12, as the major molecular marker of
      this novel apoptotic pathway, may be activated and involved in the pathogenesis
      of apoptotic injury after SAH. This study sought to investigate the changes of
      caspase-12 expressions in both in vitro and in vivo SAH models. Western blot
      analysis found significantly increased protein expressions of both pro- and
      active forms of caspase-12 after SAH. Quantitative real-time PCR and
      immunohistochemistry assays confirmed elevated caspase-12 level after SAH in
      vivo. Further, double immunofluorescence staining revealed obvious caspase-12
      over-expression in both cortical neurons and astrocytes. Moreover,
      immunofluorescent co-staining in vivo demonstrated that neural cells with high
      immunoreactivity of caspase-12 also expressed caspase-3, and dual
      immunofluorescent staining for caspase-12 and TUNEL in vitro showed that TUNEL
      positive cells were more likely to exhibit higher caspase-12 immunoreactivity,
      indicating a potential contribution of caspase-12 activation to apoptosis in SAH.
      Collectively, our results showed significant upregulation of caspase-12
      expression after experimental SAH. These findings also offer important
      implications for further investigations of the therapeutic potential of caspase
      12 associated apoptosis in SAH.

PMID- 27718043
TI  - Bacteriophages and its applications: an overview.
AB  - Bacteriophages (or phages), the most abundant viral entity of the planet, are
      omni-present in all the ecosystems. On the basis of their unique characteristics
      and anti-bacterial property, phages are being freshly evaluated taxonomically.
      Phages replicate inside the host either by lytic or lysogenic mode after
      infecting and using the cellular machinery of a bacterium. Since their discovery
      by Twort and d'Herelle in the early 1900s, phage became an important agent for
      combating pathogenic bacteria in clinical treatments and its related research
      gained momentum. However, due to recent emergence of bacterial resistance on
      antibiotics, applications of phage (phage therapy) become an inevitable option of
      research. Phage particles become popular as a biotechnological tool and treatment
      of pathogenic bacteria in a range of applied areas. However, there are few
      concerns over the application of phage-based solutions. This review deals with
      the updated phage taxonomy (ICTV 2015 Release and subsequent revision) and phage
      biology and the recent development of its application in the areas of
      biotechnology, biosensor, therapeutic medicine, food preservation, aquaculture
      diseases, pollution remediation, and wastewater treatment and issues related with
      limitations of phage-based remedy.

PMID- 27718046
TI  - The Role of Ca2+ Imbalance in the Induction of Acute Oxidative Stress and
      Cytotoxicity in Cultured Rat Cerebellar Granule Cells Challenged with
      Tetrabromobisphenol A.
AB  - Using primary cultures of rat cerebellar granule cells (CGC) we examined the role
      of calcium transients induced by tetrabromobisphenol A (TBBPA) in triggering
      oxidative stress and cytotoxicity. CGC were exposed for 30 min to 10 or 25 uM
      TBBPA. Changes in intracellular calcium concentration ([Ca2+]i), in the
      production of reactive oxygen species (ROS), and in the potential of mitochondria
      (?Psim) were measured fluorometrically during the exposure. The intracellular
      glutathione (GSH) and catalase activity were determined after the incubation;
      cell viability was evaluated 24 h later. TBBPA concentration-dependently
      increased [Ca2+]i and ROS production, and reduced GSH content, catalase activity,
      ?Psim and neuronal viability. The combination of NMDA and ryanodine receptor
      antagonists, MK-801 and bastadin 12 with ryanodine, respectively, prevented Ca2+
      transients and partially reduced cytotoxicity induced by TBBPA at both
      concentrations. The antagonists also completely inhibited oxidative stress and
      depolarization of mitochondria evoked by 10 uM TBBPA, whereas these effects were
      only partially reduced in the 25 uM TBBPA treatment. Free radical scavengers
      prevented TBBPA-induced development of oxidative stress and improved CGC
      viability without having any effect on the rises in Ca2+ and drop in ?Psim. The
      co-administration of scavengers with NMDA and ryanodine receptor antagonists
      provided almost complete neuroprotection. These results indicate that Ca2+
      imbalance and oxidative stress both mediate acute toxicity of TBBPA in CGC. At 10
      uM TBBPA Ca2+ imbalance is a primary event, inducing oxidative stress,
      depolarization of mitochondria and cytotoxicity, whilst at a concentration of 25
      uM TBBPA an additional Ca2+-independent portion of oxidative stress and
      cytotoxicity emerges.

PMID- 27718047
TI  - Generation and evaluation of a genetically attenuated Newcastle disease virus rGM
      VIIm as a genotype-matched vaccine.
AB  - Despite intensive vaccination campaigns, outbreaks of Newcastle disease (ND) have
      been frequently reported in China, especially of genotype VII that first emerged
      in the late 1990s. Given the dire need for vaccines against the circulating
      genotype VII virus, we developed an alternative method to recover a highly
      virulent recombinant GM (rGM) virus that involves a T7 system with a hammerhead
      ribozyme sequence introduced downstream of the T7 promoter. By changing the F0
      polybasic cleavage site RRQKR?F to the monobasic GRQGR?L, we generated a mutant
      virus (rGM-VIIm) that was found to be highly attenuated in chickens. The rGM-VIIm
      virus not only produced fourfold higher hemagglutination assay (HA) titers than
      the parental virus, but also exhibited genetic stability after 15 continuous
      passages in specific-pathogen-free (SPF) embryonated eggs. Whether live or
      inactivated, rGM-VIIm and LaSota vaccines can protect vaccinated birds from GM
      challenge infection. However, live and inactivated rGM-VIIm vaccines reduced
      virus shedding of the homologous challenge virus significantly better than the
      LaSota virus vaccine did. Altogether, our results suggest that rGM-VIIm vaccines
      could aid in the control of ND in China.

PMID- 27718048
TI  - Neighborhood Socioeconomic Status and Primary Health Care: Usual Points of Access
      and Temporal Trends in a Major US Urban Area.
AB  - Neighborhood socioeconomic status (SES), an overall marker of neighborhood
      conditions, may determine residents' access to health care, independently of
      their own individual characteristics. It remains unclear, however, how the
      distinct settings where individuals seek care vary by neighborhood SES,
      particularly in US urban areas. With existing literature being relatively old,
      revealing how these associations might have changed in recent years is also
      timely in this US health care reform era. Using data on the Philadelphia region
      from 2002 to 2012, we performed multilevel analysis to examine the associations
      of neighborhood SES (measured as census tract median household income) with
      access to usual sources of primary care (physician offices, community health
      centers, and hospital outpatient clinics). We found no evidence that residence in
      a low-income (versus high-income) neighborhood was associated with poorer overall
      access. However, low-income neighborhood residence was associated with less
      reliance on physician offices [-4.40 percentage points; 95 % confidence intervals
      (CI) -5.80, -3.00] and greater reliance on the safety net provided by health
      centers [2.08; 95 % CI 1.42, 2.75] and outpatient clinics [1.61; 95 % CI 0.97,
      2.26]. These patterns largely persisted over the 10 years investigated. These
      findings suggest that safety-net providers have continued to play an important
      role in ensuring access to primary care in urban, low-income communities, further
      underscoring the importance of supporting a strong safety net to ensure equitable
      access to care regardless of place of residence.

PMID- 27718049
TI  - Diagnosis of early colorectal cancer invasion depth by quantitative evaluation of
      the basal indentation in CT colonography.
AB  - OBJECTIVE: To investigate the feasibility of diagnosing the invasion depth of
      early colorectal cancer (CRC) by quantitatively evaluating the basal indentation
      (BI)-i.e., the intestinal lateral deformity-in CT colonography (CTC). MATERIALS
      AND METHODS: 34 early CRCs (13 Tis CRCs and 21 T1 CRCs) in 32 patients who
      underwent a preoperative CTC were retrospectively examined. Two radiologists
      calculated the depth of the BI on a computed tomographic air-contrast enema (CT
      enema) image, the depth of the BI due to the geometric function (BI-G) on a cross
      sectional multiplanar reconstruction (CS-MPR) image, and the ratio of the BI to
      the BI-G (i.e., the "BI ratio") for each lesion. The BI ratios of the Tis and T1
      CRCs were compared. RESULTS: The BI ratios were significantly higher in the T1
      CRCs than in the Tis CRCs (p < 0.0001). The optimum cutoff value of the BI ratio
      for differentiating the T1 CRCs from the Tis CRCs was 1.64, with a sensitivity,
      specificity, and area under the curve of 90.5 %, 100 %, and 0.974, respectively.
      CONCLUSIONS: We have demonstrated for the first time that quantitatively
      evaluating the BI can improve the accuracy of diagnosis of early CRC invasion
      depth.

PMID- 27718050
TI  - Prevalence and Control of Hypertension in Different Macro-Areas in Italy:
      Analysis of a Large Database by the General Practice.
AB  - INTRODUCTION: Limited data are available on the impact of hypertension in the
      different regions or urban areas in Italy. AIM: To evaluate hypertension
      prevalence and control among adult outpatients followed by general practitioners
      (GPs) in different regions and macro-areas in our Country. METHODS: We
      retrospectively analysed data extracted in 2013 from the national GP Health
      Search-CSD database and stratified into three groups, depending on their own
      regions (North, Center and South). Hypertension prevalence was estimated within
      the overall population sample of adult individuals, whereas control was assessed
      in hypertensive outpatients. Hypertension diagnosis was defined according to
      International Classification of Diseases 9. Clinic blood pressure (BP) levels
      were measured according to European guidelines. BP control was defined as BP
      <140/90 mmHg. RESULTS: Data from 940,806 individuals (52.0 % female) were
      scrutinized, among whom 363,324 (38.6 %) subjects were residents in the North,
      276,643 (29.4 %) in the Center and 300,839 (32.0 %) in the South. Overall
      hypertension prevalence was higher in North (36.8 %) compared to South (33.8 %)
      and Center (29.3 %). Controlled BP levels were more frequently registered in the
      South (66.3 %) compared to Center (60.7 %) and North (55.6 %). In all these
      areas, prevalence and control of hypertension were higher in female than in male
      individuals. CONCLUSIONS: The present analysis demonstrates relevant differences
      in hypertension prevalence and control among different macro-areas and regions in
      Italy. Such analysis may be useful for promoting strategies aimed at ameliorating
      hypertension control at local levels.

PMID- 27718053
TI  - ?

PMID- 27718052
TI  - [Reliability and construct validity of the OPD-CA axes: structure and
      prerequisites for treatment].
AB  - BACKGROUND: The aim of this study was to compare the Operationalized
      Psychodynamic Diagnostics (OPD-CA) for children and adolescents with the modified
      version (OPD-CA-2) focusing on the mainly unchanged treatment conditions and the
      redesigned structure axis. METHODS: The patient sample consisted 371 inpatient
      children and adolescents with psychiatric disorders from 3 to 18 years. OPD-CA
      and OPD-CA-2 diagnostics were routinely performed by OPD-experienced raters.
      Statistical calculation included Cronbach's alpha (internal consistency) and
      confirmatory factor analysis. RESULTS: The OPD-CA-2 structure axis showed very
      good internal consistency (reliability) compared to the OPD-CA. We found
      satisfactorily good values for the treatment conditions with slightly higher
      average scores in the OPD-CA-2. Confirmatory factor analysis resulted in two
      models where the items on the OPD-CA-2 structure axis were stronger correlated
      than those of the OPD-CA. CONCLUSION: The OPD-CA-2 is a reliable and valid
      instrument for assessing treatment conditions and psychic structure in children
      and adolescents. The reorganization of the structure axis and the treatment
      conditions in the OPD-CA-2 resulted in a measurable improvement.

PMID- 27718054
TI  - Anesthesia scavenging in critical care areas: beware of possible hazards and
      questionable efficacy.

PMID- 27718056
TI  - Role of the Histamine H4-Receptor in Bronchial Asthma.
AB  - Histamine is a pro-inflammatory mediator with a prominent role in allergic
      diseases. Antagonists at the histamine receptor subtype 1 are central in anti
      allergic therapies, with the exception of allergic asthma, where they are
      clinically without effect. The latest identified histamine receptor subtype 4,
      which is expressed mainly in hematopoietic cells, now provides a reasonable
      target for new therapeutic strategies inhibiting histamine function. The
      pathophysiology of allergy, esp. allergic asthma, and in its context the effects
      of antagonists at the histamine receptor subtype 4 in preclinical and clinical
      settings are discussed in this chapter.

PMID- 27718055
TI  - In reply: Anesthesia scavenging in critical care areas: beware of possible
      hazards and questionable efficacy.

PMID- 27718057
TI  - Delta Opioid Pharmacology in Parkinson's Disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder that
      compromises multiple neurochemical substrates including dopamine, norepinephrine,
      serotonin, acetylcholine, and glutamate systems. Loss of these transmitter
      systems initiates a cascade of neurological deficits beginning with motor
      function and ending with dementia. Current therapies primarily address the motor
      symptoms of the disease via dopamine replacement therapy. Exogenous dopamine
      replacement brings about additional challenges since after years of treatment it
      almost invariably gives rise to dyskinesia as a side effect. Therefore there is a
      clear unmet clinical need for improved PD therapeutics. Opioid receptors and
      their respective peptides are expressed throughout the basal ganglia and cortex
      where monoaminergic denervation strongly contributes to PD pathology. Delta
      opioid receptors are of particular interest because of their dense localization
      in basal ganglia and because activating this system is known to enhance locomotor
      activity under a variety of conditions. This chapter will outline much of the
      work that has demonstrated the effectiveness of delta opioid receptor activation
      in models of PD and its neuroprotective properties. It also discusses some of the
      challenges that must be addressed before moving delta opioid receptor agonists
      into a clinical setting.

PMID- 27718058
TI  - Mitochondrial Changes in Cancer.
AB  - Mitochondrial structural and functional integrity defines the health of a cell by
      regulating cellular metabolism. Thus, mitochondria play an important role in both
      cell proliferation and cell death. Cancer cells are metabolically altered
      compared to normal cells for their ability to survive better and proliferate
      faster. Resistance to apoptosis is an important characteristic of cancer cells
      and given the contribution of mitochondria to apoptosis, it is imperative that
      mitochondria could behave differently in a tumor situation. The other feature
      associated with cancer cells is the Warburg effect, which engages a shift in
      metabolism. Although the Warburg effect often occurs in conjunction with
      dysfunctional mitochondria, the relationship between mitochondria, the Warburg
      effect, and cancer cell metabolism is not clearly decoded. Other than these
      changes, several mitochondrial gene mutations occur in cancer cells,
      mitochondrial biogenesis is affected and mitochondria see structural and
      functional variations. In cancer pharmacology, targeting mitochondria and
      mitochondria associated signaling pathways to reduce tumor proliferation is a
      growing field of interest. This chapter summarizes various changes in
      mitochondria in relevance to cancer, behavior of mitochondria during
      tumorigenesis, and the progress on using mitochondria as a therapeutic target for
      cancer.

PMID- 27718060
TI  - Platelet-Derived Growth Factor in Heart Failure.
AB  - Defective vascular and cardiomyocyte function are implicated in the development
      and progression of both heart failure with reduced and preserved ejection
      fraction. Any treatment option that augments these myocardial processes may
      therefore be of significant value. The platelet-derived growth factor (PDGF)
      family is involved in a wide range of growth processes and plays a key role in
      both regulating angiogenesis and mesenchymal cell development. Thus, PDGF may
      serve as a potent therapy for heart failure. While numerous animal studies have
      demonstrated beneficial cardiovascular effects of growth factor therapy,
      promising laboratory data has not yet translated to effective therapies. In this
      review, we outline the biological role of PDGF and summarize previous studies
      that have focused on the cardiovascular effects of normal PDGF signaling,
      administration of PDGF, and the effects of PDGF on stem cell therapy.

PMID- 27718059
TI  - Epidemiology of Heart Failure.
AB  - Heart failure (HF) is a major public health problem affecting more than 23
      million patients worldwide. Incidence and prevalence rates vary significantly
      according to the source of data, but both increase with advancing age reaching,
      in the very elderly, prevalence rates that represent a challenge for the
      organization of medical care systems. Even if evidence-based treatments have
      improved prognosis in some patients with HF, patients with HF still need to be
      carefully characterized, described, and treated. Hospitalizations for acute HF
      are frequent and costly accounting for the vast majority of HF-related costs.

PMID- 27718061
TI  - Society of behavioral medicine supports increasing HPV vaccination uptake: an
      urgent opportunity for cancer prevention.
AB  - Human papillomavirus (HPV) vaccine coverage remains low in the USA. The Society
      for Behavioral Medicine (SBM) supports the goals outlined by Healthy People 2020,
      the President's Cancer Panel, and the National Vaccine Advisory Committee to
      increase vaccination coverage among both males and females. SBM makes the
      following recommendations in support of efforts to reduce structural and other
      barriers to HPV vaccination services in order to increase rates of series
      completion. We encourage legislators and other policymakers to improve
      administration authority, insurance coverage, and reimbursement rates to
      healthcare providers who make the HPV vaccine available to adolescents; provide
      instrumental support to fund the development of school curricula on HPV
      vaccination; and increase public awareness that HPV vaccination can prevent
      cancer. We urge healthcare providers and healthcare systems to increase the
      strength, quality, and consistency of HPV vaccination recommendations for all
      eligible patients; to treat HPV vaccination as a routine preventive service;
      employ culturally appropriate communication strategies in clinical settings to
      educate eligible patients, parents, and guardians about the importance,
      effectiveness, and safety of HPV vaccination; and to strengthen and better
      coordinate the use of electronic medical records and immunization information
      systems.

PMID- 27718062
TI  - Predictors of and health- and fall-related program outcomes resulting from
      complete and adequate doses of a fall risk reduction program.
AB  - Falls are dangerous and costly for older adults. The A Matter of
      Balance/Volunteer Lay Leader (AMOB/VLL) program is an evidence-based fall risk
      reduction program that could help reduce this burden. This study introduced a
      door-through-door transportation program to improve program delivery (N = 126).
      Characteristics predicting completion of all eight AMOB/VLL sessions were
      identified using logistic regression. Individual growth models were employed to
      determine the immediate, intermediate, and long-term goal outcomes resulting from
      receiving an adequate dose of the program (five to eight sessions). Self
      restriction of activities due to fear of falling (OR 5.04, 95 % CI 1.86-13.69)
      and a lower frequency of moderate and vigorous physical activity (OR 1.14, 95 %
      CI 1.04-1.27) were significantly predictive of receiving a complete dose. Three
      outcome goals were significant, including (1) immediate-improved self-efficacy of
      managing medications and treatments, (2) intermediate-reduced activity
      limitations, and (3) intermediate-reduced physical disability. Self-restriction
      of activities due to a fear of falling and physical activity levels may be simple
      and effective screening questions to prevent AMOB/VLL attrition. In our study,
      those who did receive the program improved on a specific type of self-efficacy
      and on self-reported physical functioning.

PMID- 27718063
TI  - Strategies of chemical anti-predator defences in leaf beetles: is sequestration
      of plant toxins less costly than de novo synthesis?
AB  - The evolution of defensive traits is driven both by benefits gained from
      protection against enemies and by costs of defence production. We tested the
      hypothesis that specialisation of herbivores on toxic host plants, accompanied by
      the ability to acquire plant defensive compounds for herbivore defence, is
      favoured by the lower costs of sequestration compared to de novo synthesis of
      defensive compounds. We measured physiological costs of chemical defence as a
      reduction in larval performance in response to repeated removal of secretions
      (simulating predator attack) and compared these costs between five species
      synthesising defences de novo and three species sequestering salicylic glucosides
      (SGs) from their host plants. Experiments simulating low predator pressure
      revealed no physiological costs in terms of survival, weight and duration of
      development in any of study species. However, simulation of high predation caused
      reduction in relative growth rate in Chrysomela lapponica larvae producing
      autogenous defences more frequently, than in larvae sequestering SGs. Still meta
      analysis of combined data showed no overall difference in costs of autogenous and
      sequestered defences. However, larvae synthesising their defences de novo
      demonstrated secretion-conserving behaviour, produced smaller amounts of
      secretions, replenished them at considerably lower rates and employed other types
      of defences (regurgitation, evasion) more frequently when compared to
      sequestering larvae. These latter results provide indirect evidence for
      biosynthetic constraints for amounts of defensive secretions produced de novo,
      resulting in low defence effectiveness. Lifting these constraints by
      sequestration may have driven some leaf beetle lineages toward sequestration of
      plant allelochemicals as the main defensive strategy.

PMID- 27718064
TI  - Enhanced leaf nitrogen status stabilizes omnivore population density.
AB  - Plant traits can mediate the strength of interactions between omnivorous
      predators and their prey through density effects and changes in the omnivores'
      trophic behavior. In this study, we explored the established assumption that
      enhanced nutrient status in host plants strengthens the buffering effect of plant
      feeding for omnivorous predators, i.e., prevents rapid negative population growth
      during prey density decline and thereby increases and stabilizes omnivore
      population density. We analyzed 13 years of field data on population densities of
      a heteropteran omnivore on Salix cinerea stands, arranged along a measured leaf
      nitrogen gradient and found a 195 % increase in omnivore population density and a
      63 % decrease in population variability with an increase in leaf nitrogen status
      from 26 to 40 mgN * g-1. We recreated the leaf nitrogen gradient in a greenhouse
      experiment and found, as expected, that increasing leaf nitrogen status enhanced
      omnivore performance but reduced per capita prey consumption. Feeding on high
      nitrogen status host plants can potentially decouple omnivore-prey population
      dynamics and allow omnivores to persist and function effectively at low prey
      densities to provide "background level" control of insect herbivores. This long
      term effect is expected to outweigh the short-term effect on per capita prey
      consumption-resulting in a net increase in population predation rates with
      increasing leaf nitrogen status. Conservation biological control of insect pests
      that makes use of omnivore background control could, as a result, be manipulated
      via management of crop nitrogen status.

PMID- 27718066
TI  - Joint effects of resources and amphibians on pond ecosystems.
AB  - Primary production can be controlled through bottom-up (e.g., resources) or top
      down (e.g., predators) constraints. Two key bottom-up resources in small aquatic
      systems are light and nutrients, and forest canopy cover heavily influences these
      factors, whereas amphibian and invertebrate colonizers exert top-down pressure as
      grazers and predators. We designed our experiment to specifically manipulate two
      different top-down and bottom-up factors. We manipulated resources by altering
      light (low/high) and nutrient (low/high) availability; omnivores with the
      presence/absence of southern leopard frog tadpoles (Lithobates sphenocephalus);
      and predators with the presence/absence of spotted salamander larvae (Ambystoma
      maculatum) in a full-factorial experiment conducted over 14 weeks. We observed
      that both bottom-up and top-down effects were important in predicting lower
      trophic level biomass. We found a significant top-down effect of salamanders on
      Daphnia, but tadpoles had the strongest overall effect on the food web,
      influencing phytoplankton (+), periphyton (-), and chironomids (-). None of our
      models were good predictors of phytoplankton biomass, but both shading and
      nutrient availability relatively equally boosted periphyton biomass. We also
      found large temporal differences in food-web dynamics. Our results underscore the
      need for more information into how ecosystem functioning could be altered by land
      use, amphibian extirpation, and climate change.

PMID- 27718065
TI  - Seasonal fecundity is not related to geographic position across a species' global
      range despite a central peak in abundance.
AB  - The range of a species is determined by the balance of its demographic rates
      across space. Population growth rates are widely hypothesized to be greatest at
      the geographic center of the species range, but indirect empirical support for
      this pattern using abundance as a proxy has been mixed, and demographic rates are
      rarely quantified on a large spatial scale. Therefore, the texture of how
      demographic rates of a species vary over its range remains an open question. We
      quantified seasonal fecundity of populations spanning the majority of the global
      range of a single species, the saltmarsh sparrow (Ammodramus caudacutus), which
      demonstrates a peak of abundance at the geographic center of its range. We used a
      novel, population projection method to estimate seasonal fecundity inclusive of
      seasonal and spatial variation in life history traits that contribute to seasonal
      fecundity. We replicated our study over 3 years, and compared seasonal fecundity
      to latitude and distance among plots. We observed large-scale patterns in some
      life history traits that contribute to seasonal fecundity, such as an increase in
      clutch size with latitude. However, we observed no relationship between latitude
      and seasonal fecundity. Instead, fecundity varied greatly among plots separated
      by as little as 1 km. Our results do not support the hypothesis that demographic
      rates are highest at the geographic and abundance center of a species range, but
      rather they suggest that local drivers strongly influence saltmarsh sparrow
      fecundity across their global range.

PMID- 27718067
TI  - Dermatologic events from EGFR inhibitors: the issue of the missing patient voice.
AB  - PURPOSE: As epidermal growth factor receptor (EGFR) inhibitors are associated
      with a variety of dermatologic adverse events (dAEs), the purpose of this study
      was to develop an overview of current knowledge of dAEs associated with EGFR
      inhibitors and to identify knowledge gaps regarding incidence, treatment, impact
      on quality of life (QOL), and patient acceptance. METHOD: A structured literature
      search was conducted using MEDLINE/PubMed (January 1983 to January 2014). In
      total, 71 publications published from 2004 to 2014 were identified for
      consideration in the final evidence review. RESULTS: The majority of published
      articles concentrate on the incidence of skin reactions, duration, treatment, and
      prevention strategies. Different grading systems based on the symptoms of skin
      rash or on health-related QOL (HRQOL) are used. An additional topic is the
      possible correlation between acneiform rash and efficacy of EGFR inhibitors.
      Knowledge gaps identified in the literature were how dAEs impact QOL compared
      with other AEs from a patient's perspective, patients' acceptance of dAEs
      (willingness to tolerate), and the impact of physician-patient communication on
      treatment decisions. CONCLUSIONS: Research is needed on the impact of dAEs on
      patients' acceptance of cancer treatments. Systematic studies are missing that
      compare the impact of dAEs with other toxicities on therapy decisions from both
      physician's and patient's view, and that investigate the balance between efficacy
      and avoidance of acneiform rash in treatment decisions. Such studies could
      provide deeper insights into the acceptance of the risk of untoward dermatologic
      events by both physicians and patients when treating advanced cancers.

PMID- 27718068
TI  - Advance directives in patients with advanced cancer receiving active treatment:
      attitudes, prevalence, and barriers.
AB  - PURPOSE: The purposes of the study were to assess awareness and prevalence of
      advance directives (ADs) among patients with advanced cancer undergoing active
      outpatient care and to determine factors associated with AD completion before and
      after the diagnosis of cancer. METHODS: Patients with advanced solid tumor
      malignancy receiving treatment at the Chemotherapy Day Unit were approached for
      recruitment. They completed an onsite questionnaire about completion and timing
      of ADs, demographic information, and perceived health; a review of their medical
      records was conducted to document their cancer care and co-morbidities.
      Multinomial logistic regression analysis identified factors associated with the
      timing of AD completion (pre-cancer, post-cancer, or not at all). RESULTS: Two
      hundred patients were enrolled, with 193 surveys available for analysis. ADs were
      completed in 55 % (106/193) of patients, including a living will in 33 %
      (63/193), a power of attorney in 49 % (95/193), and a do-not-resuscitate (DNR)
      designation in 18 % (35/193). Most patients (53 %) had completed an AD before
      being diagnosed with cancer. Higher income (p = 0.02) and age (p = 0.004) were
      associated with AD completion pre-cancer diagnosis; discussion of end-of-life
      care (p = 0.02) and palliative care referral (p < 0.0001) were associated with AD
      completion post-cancer diagnosis. CONCLUSIONS: This study demonstrates that
      different factors may influence the completion of ADs before and after a
      diagnosis of cancer and highlights the potential for early palliative care to
      impact the completion of ADs in patients with advanced cancer who are undergoing
      active cancer treatment.

PMID- 27718069
TI  - Comparative analysis of bleeding risk by the location and shape of arachnoid
      cysts: a finite element model analysis.
AB  - OBJECTIVE: Although arachnoid cysts (ACs) are observed in various locations, only
      sylvian ACs are mainly regarded to be associated with bleeding. The reason for
      this selective association of sylvian ACs with bleeding is not understood well.
      This study is to investigate the effect of the location and shape of ACs on the
      risk of bleeding. METHODS: A developed finite element model of the head/brain was
      modified for models of sylvian, suprasellar, and posterior fossa ACs. A spherical
      AC was placed at each location to compare the effect of AC location. Bowl-shaped
      and oval-shaped AC models were developed to compare the effect by shape. The
      shear force on the spot-weld elements (SFSW) was measured between the dura and
      the outer wall of the ACs or the comparable arachnoid membrane in the normal
      model. RESULTS: All AC models revealed higher SFSW than comparable normal models.
      By location, sylvian AC displayed the highest SFSW for frontal and lateral
      impacts. By shape, small outer wall AC models showed higher SFSW than large wall
      models in sylvian area and lower SFSW than large ones in posterior fossa. In
      regression analysis, the presence of AC was the only independent risk of
      bleeding. CONCLUSION: The bleeding mechanism of ACs is very complex, and the risk
      quantification failed to show a significant role of location and shape of ACs.
      The presence of AC increases shear force on impact condition and may be a risk
      factor of bleeding, and sylvian location of AC may not have additive risks of AC
      bleeding.

PMID- 27718070
TI  - Neurological assessment of Chinese infants with positional plagiocephaly using a
      Chinese version of the Infant Neurological International Battery (INFANIB).
AB  - PURPOSE: Positional plagiocephaly (PP) is the most common subtype of asymmetric
      deformity in the infant skull. Cumulative evidence has demonstrated that PP is
      associated with abnormal neuromotor development; however, neurological assessment
      scores of infants with PP have not been well established, and PP has not
      attracted sufficient attention in China. This study used a Chinese version of the
      Infant Neurological International Battery (INFANIB) to identify neurological
      abnormalities among infants with PP and to determine the differences between
      infants with different (mild, moderate, and severe) degrees of PP. METHODS: We
      compared the neurological evaluation scores between 393 infants with different
      degrees of PP and 390 healthy infants from 0 to 18 months of age using a Chinese
      version of the INFANIB. RESULTS: The infants with PP aged 0-7.9 months had lower
      scores on the spasticity, head and trunk, leg, and French angle subscales and
      lower total scores than the normal infants. Additionally, the infants with PP
      aged 9-18 months showed statistically significantly lower scores on the
      spasticity, head and trunk, vestibular function, leg, and French angle subscales
      and total scores than the normal infants. Among the PP subgroups, the infants
      with mild PP had the highest scores, followed by the infants with moderate PP and
      the infants with severe PP. Compared with the normal infants, the infants with PP
      had abnormal neurological assessment scores, and the degree of neurological
      abnormality was associated with the severity of PP. CONCLUSIONS: The INFANIB
      revealed neurological abnormalities, including asymmetric movements and abnormal
      muscle tone, postures, and reflexes, in infants with PP, especially those with
      moderate or severe PP. These abnormalities were similar to those of infants with
      cerebral palsy. Therefore, PP may serve as a marker of neurodevelopmental risk
      and should receive considerable attention. Whether moderate or severe PP is
      related to cerebral palsy remains to be confirmed in long-term follow-up studies
      and other future studies.

PMID- 27718071
TI  - The efficacy of fidaxomicin in the treatment of Clostridium difficile infection
      in a real-world clinical setting: a Spanish multi-centre retrospective cohort.
AB  - The objective of this study was to evaluate the efficacy and safety of
      fidaxomicin in the real-life clinical setting. This was a retrospective cohort of
      patients with Clostridium difficile infection (CDI) treated with fidaxomicin in
      20 Spanish hospitals between July 2013 and July 2014. Clinical cure, 30-day
      recurrence, 30-day mortality, sustained cure, and factors associated with the
      failure to achieve sustained cure were analyzed. Of the 72 patients in the cohort
      41 (56.9 %) had a fatal underlying disease. There were 44 (61.1 %) recurrent
      episodes and 26 cases (36.1 %) with a history of multiple recurrences. Most
      episodes were severe (26, 36 %) or severe-complicated (14, 19.4 %). Clinical cure
      rate was 90.3 %, recurrence rate was 16.7 % and three patients (4.2 %) died
      during the follow-up period. Sustained cure was achieved in 52 cases (72.2 %).
      Adverse events were reported in five cases (6.9 %). Factors associated with the
      lack of sustained cure were cardiovascular comorbidity (OR 11.4; 95 %CI 1.9
      67.8), acute kidney failure (OR 7.4; 95 %CI 1.3-43.1), concomitant systemic
      antibiotic treatment (OR 6.2; 95 %CI 1.1-36.8), and C-reactive protein value at
      diagnosis (OR 1.2 for each 1 mg/dl increase; 95 %CI 1.03-1.3). Fidaxomicin is an
      effective and well tolerable treatment for severe CDI and for cases with elevated
      recurrence risk.

PMID- 27718073
TI  - Whole-genome characterisation of G12P[6] rotavirus strains possessing two
      distinct genotype constellations co-circulating in Blantyre, Malawi, 2008.
AB  - Rotavirus A strains detected in diarrhoeal children commonly possess any one of
      the genotypes G1, G2, G3, G4, and G9, with a recent increase in G12 detection
      globally. G12P[6] strains possessing short RNA (DS-1-like) and long RNA (Wa-like)
      migration patterns accounted for 27 % of the strains circulating in Blantyre,
      Malawi, between 2007 and 2008. To understand how the G12P[6] strains with two
      distinct genetic backgrounds emerged in Malawi, we conducted whole-genome
      analysis of two long-RNA and two short-RNA strains. While the former had a
      typical Wa-like genotype constellation of G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1,
      the latter was found to have G12-P[6]-I2-R2-C2-M1-A2-N2-T2-E2-H2: a VP3 gene mono
      reassortant on the DS-1-like backbone. Phylogenetic and Bayesian Markov chain
      Monte Carlo analyses showed that the short-RNA G12P[6] strains were generated
      around 2006 by reassortment between an African Wa-like G12P[6] strain donating
      three genes (the VP7, VP4, and VP3 genes) and a G2P[4] strain similar to the one
      circulating in Thailand or the United States of America that donated the
      remaining eight genes. On the other hand, the long-RNA strains were generated as
      a result of reassortment events within Wa-like G12 and non-G12 strains commonly
      circulating in Africa; only the VP4 gene was from a Malawian G8P[6] strain. In
      conclusion, this study uncovered the evolutionary pathways through which two
      distinct G12P[6] strains emerged in Malawi.

PMID- 27718072
TI  - Acrolein-detoxifying isozymes of glutathione transferase in plants.
AB  - MAIN CONCLUSION: Acrolein is a lipid-derived highly reactive aldehyde, mediating
      oxidative signal and damage in plants. We found acrolein-scavenging glutathione
      transferase activity in plants and purified a low K M isozyme from spinach.
      Various environmental stressors on plants cause the generation of acrolein, a
      highly toxic aldehyde produced from lipid peroxides, via the promotion of the
      formation of reactive oxygen species, which oxidize membrane lipids. In mammals,
      acrolein is scavenged by glutathione transferase (GST; EC 2.5.1.18) isozymes of
      Alpha, Pi, and Mu classes, but plants lack these GST classes. We detected the
      acrolein-scavenging GST activity in four species of plants, and purified an
      isozyme showing this activity from spinach (Spinacia oleracea L.) leaves. The
      isozyme (GST-Acr), obtained after an affinity chromatography and two ion exchange
      chromatography steps, showed the K M value for acrolein 93 MUM, the smallest
      value known for acrolein-detoxifying enzymes in plants. Peptide sequence homology
      search revealed that GST-Acr belongs to the GST Tau, a plant-specific class. The
      Arabidopsis thaliana GST Tau19, which has the closest sequence similar to spinach
      GST-Acr, also showed a high catalytic efficiency for acrolein. These results
      suggest that GST plays as a scavenger for acrolein in plants.

PMID- 27718074
TI  - Characterization of hepatitis B virus infection in illicit drug users in the
      Marajo Archipelago, northern Brazil.
AB  - South America is considered to have a low prevalence of hepatitis B virus (HBV)
      infection, although areas with a relatively high prevalence have been identified
      in northern Brazil. Few epidemiological studies of populations at risk of HBV
      infection are available for this region. Given this, in the present study, we
      investigated the prevalence of HBV and the factors associated with infection
      among illicit drug users (DUs) in the Marajo Archipelago, northern Brazil. In
      this cross-sectional study, we collected samples and epidemiological information
      from DUs in 11 municipalities of the Marajo Archipelago. The diagnosis was
      established by ELISA and real-time PCR; and genotyping was done by multiplex real
      time PCR. Statistical modeling was based on simple and multiple logistical
      regressions with the Hosmer-Lemeshow test. The mean age of the 466 DUs was 28.4
      years, and most were male. The most-consumed illicit drugs were crack cocaine and
      marijuana. In all, 171 DUs were exposed to HBV, with genotypes A, D and F being
      identified. The factors associated with higher frequencies of HBV infection were
      (i) male gender, (ii) age above 35 years, (iii) anti-HIV positivity, (iv)
      tattoos, (v) the use of injected drugs, (vi) the use of illicit drugs for more
      than 3 years, (vii) sexual relations without protection, (viii) sexual relations
      with another DU, and (ix) more than 10 sexual partners in the past 24 months. In
      summary, this study provides important insights into the dynamics of HBV
      infection among DUs in the Marajo Archipelago. We hope that these findings will
      contribute to the development of strategies, actions and public health policies
      aimed at preventing and controlling this viral infection more effectively.

PMID- 27718076
TI  - Site of metastasis and breast cancer mortality: a Danish nationwide registry
      based cohort study.
AB  - Survival among patients with metastatic breast cancer may vary according to the
      site of metastasis and receptor status. We used Danish nationwide medical
      registries to establish a cohort of patients with metastatic breast cancer (870
      with de novo metastatic disease and 3518 with recurrent disease with distant
      metastasis) diagnosed during 1997-2011. We examined 1-year and >1 to 5-year
      mortality associated with first site of metastasis and receptor expression status
      of the primary tumor. Cox proportional regression was used to compute confounder
      adjusted mortality rate ratios (MRRs) associated with site of metastasis,
      stratified by receptor status. Overall 1-year and >1 to 5-year mortality risks
      were 36 and 69 %, respectively. Risk of death within 1 year was highest for brain
      only (62 %) and liver-only (43 %) involvement and nearly the same for patients
      with lung-only (32 %), bone-only (32 %) involvement, and other/combination of
      sites (34 %). Using bone-only metastasis as reference, women with brain-only
      metastasis had more than two-fold increased risk of dying. The adjusted MRR for
      women with liver-only metastasis also was increased, though less pronounced.
      Patients with lung-only [adjusted MRR 0.9 (95 % confidence interval (CI) 0.8,
      1.1)] or other metastases [adjusted MRR 1.0 (95 % CI 0.9, 1.2)] had similar
      mortality as patients with bone-only metastasis. Positive hormonal receptor
      status was a favorable prognostic factor. Metastatic breast cancer has a serious
      prognosis. Patients with brain-only metastasis had the highest mortality.
      Positive hormonal receptor status on the primary tumor was a favorable prognostic
      factor for all metastatic sites.

PMID- 27718075
TI  - The prevalence and genotype distribution of rotavirus A infection among children
      with acute gastroenteritis in Kunming, China.
AB  - The aim of this study was to determine the prevalence of rotavirus A (RVA)
      infections in children from Kunming, China, and the RVA genotypes present. A
      total of 16,311 children with acute gastroenteritis were recruited for the study,
      and 33.1 % (5,394/16,311) were RVA positive. Children under 24 months of age were
      more susceptible to RVA infection, with an infection rate of 87.4 %
      (4,712/5,394). The most prevalent genotype was G9P[8] (85/107, 79.4 %), which
      showed high sequence similarity to G9P[8] strains from other regions of China and
      neighbouring countries, but not to the licensed vaccine strain LLR. These
      findings should be useful for the prevention of RVA infections.

PMID- 27718077
TI  - A theoretical analysis of substituent electronic effects on phosphine-borane
      bonds.
AB  - Phosphine-borane adducts are a well-known moiety in synthetic and coordination
      chemistry. These complexes form a dative bond in which the Lewis basic phosphorus
      atom donates electron density into an empty p-orbital of the Lewis acidic boron
      atom. However, donation of the phosphorus lone pair is not the only stabilizing
      interaction, as hyperconjugation and electrostatic interaction also play
      important roles in bonding. This paper describes a detailed density functional
      theory level (B3LYP) study completed to determine the impact electron-donating
      and withdrawing substituents have on phosphine-borane bonds through the
      investigation of a series of para-substituted PAr3-BH3 and PH3-BAr3 phosphine
      borane adducts. Natural bond orbital (NBO) partitioning was used to calculate the
      distribution of electron density between the phosphine and borane fragments.
      Extended transition state and natural orbitals for chemical valence (ETS-NOCV)
      analysis was used to isolate contributions to the overall electronic interaction
      of the phosphine-borane adducts. Molecular orbital composition and charge
      donation was calculated using AOMix. The resulting data was correlated with
      Hammett sigma constants.

PMID- 27718078
TI  - Interleaving cerebral CT perfusion with neck CT angiography part I. Proof of
      concept and accuracy of cerebral perfusion values.
AB  - OBJECTIVES: We present a novel One-Step-Stroke protocol for wide-detector CT
      scanners that interleaves cerebral CTP with volumetric neck CTA (vCTA). We
      evaluate whether the resulting time gap in CTP affects the accuracy of CTP
      values. METHODS: Cerebral CTP maps were retrospectively obtained from 20 patients
      with suspicion of acute ischemic stroke and served as the reference standard. To
      simulate a 4 s gap for interleaving CTP with vCTA, we eliminated one acquisition
      at various time points of CTP starting from the bolus-arrival-time(BAT). Optimal
      timing of the vCTA was evaluated. At the time point with least errors, we
      evaluated elimination of a second time point (6 s gap). RESULTS: Mean absolute
      percentage errors of all perfusion values remained below 10 % in all patients
      when eliminating any one time point in the CTP sequence starting from the BAT.
      Acquiring the vCTA 2 s after reaching a threshold of 70HU resulted in the lowest
      errors (mean <3.0 %). Eliminating a second time point still resulted in mean
      errors <3.5 %. CBF/CBV showed no significant differences in perfusion values
      except MTT. However, the percentage errors were always below 10 % compared to the
      original protocol. CONCLUSION: Interleaving cerebral CTP with neck CTA is
      feasible with minor effects on the perfusion values. KEY POINTS: * Removing a
      single CTP acquisition has minor effects on calculated perfusion values *
      Calculated perfusion values errors depend on timing of skipping a CTP acquisition
      * Qualitative evaluation of CTP was not influenced by removing two time points *
      Neck CTA is optimally timed in the upslope of arterial enhancement.

PMID- 27718080
TI  - Prospective validation of the ultrasound based TIRADS (Thyroid Imaging Reporting
      And Data System) classification: results in surgically resected thyroid nodules.
AB  - OBJECTIVE: To assess performance of TIRADS classification on a prospective
      surgical cohort, demonstrating its clinical usefulness. METHODS: Between June
      2009 and October 2012, patients assessed with pre-operative ultrasound (US) were
      included in this IRB-approved study. Nodules were categorised according to our
      previously described TIRADS classification. Final pathological diagnosis was
      obtained from the thyroidectomy specimen. Sensitivity, specificity,
      positive/negative predictive values and likelihood ratios were calculated.
      RESULTS: The study included 210 patients with 502 nodules (average: 2.39 (+/
      1.64) nodules/patient). Median size was 7 mm (3-60 mm). Malignancy was 0 %
      (0/116) in TIRADS 2, 1.79 % (1/56) in TIRADS 3, 76.13 % (185/243) in TIRADS 4
      [subgroups: TIRADS 4A 5.88 % (1/17), TIRADS 4B 62.82 % (49/78), TIRADS 4C 91.22 %
      (135/148)], and 98.85 % (86/87) in TIRADS 5. With a cut-off point at TIRADS 4-5
      to perform FNAB, we obtained: sensitivity 99.6 % (95 % CI: 98.9-100.0),
      specificity 74.35 % (95 % CI: 68.7-80.0), PPV 82.1 % (95 % CI: 78.0-86.3), NPV
      99.4 % (95 % CI: 98.3-100.0), PLR 3.9 (95 % CI: 3.6-4.2) and an NLR 0.005 (95 %
      CI: 0.003-0.04) for malignancy. CONCLUSION: US-based TIRADS classification allows
      selection of nodules requiring FNAB and recognition of those with a low
      malignancy risk. KEY POINTS: * TIRADS classification allows accurate selection of
      thyroid nodules requiring biopsy (TIRADS 4-5). * The recognition of
      benign/possibly benign patterns can avoid unnecessary procedures. * This
      classification and its sonographic patterns are validated using surgical
      specimens.

PMID- 27718079
TI  - Breast dose reduction for chest CT by modifying the scanning parameters based on
      the pre-scan size-specific dose estimate (SSDE).
AB  - OBJECTIVE: To investigate the usefulness of modifying scanning parameters based
      on the size-specific dose estimate (SSDE) for a breast-dose reduction for chest
      CT. MATERIALS AND METHODS: We scanned 26 women with a fixed volume CT dose index
      (CTDIvol) (15 mGy) and another 26 with a fixed SSDE (15 mGy) protocol (protocol 1
      and 2, respectively). In protocol 2, tube current was calculated based on the
      patient habitus obtained on scout images. We compared the mean breast dose and
      the inter-patient breast dose variability and performed linear regression
      analysis of the breast dose and the body mass index (BMI) of the two protocols.
      RESULTS: The mean breast dose was about 35 % lower under protocol 2 than protocol
      1 (10.9 mGy vs. 16.8 mGy, p < 0.01). The inter-patient breast dose variability
      was significantly lower under protocol 2 than 1 (1.2 mGy vs. 2.5 mGy, p < 0.01).
      We observed a moderate negative correlation between the breast dose and the BMI
      under protocol 1 (r = 0.43, p < 0.01); there was no significant correlation (r =
      0.06, p = 0.35) under protocol 2. CONCLUSION: The SSDE-based protocol achieved a
      reduction in breast dose and in inter-patient breast dose variability. KEY
      POINTS: * CT scan parameters can be modified based on the pre-scan SSDE. * The
      pre-scan SSDE is useful for a breast dose reduction. * The fixed SSDE protocol
      reduced individual variations in the breast dose.

PMID- 27718081
TI  - The assessment of peripapillary retinal nerve fiber layer and macular ganglion
      cell layer changes in obese children: a cross-sectional study using optical
      coherence tomography.
AB  - PURPOSE: To investigate the relationship between the obesity and optical
      coherence tomography (OCT) parameters. METHODS: We studied 54 obese and 33 non
      obese children and adolescents. Obesity was defined as BMI higher than 95th
      percentile (BMI SDS > 1.64). OCT measurements were performed in all participants.
      Anthropometric and biochemical variables were compared with OCT parameters of 174
      eyes. RESULTS: In obese children, in all quadrants retinal nerve fiber layer
      (RNFL) thicknesses were significantly lower than non-obese children, and also
      ganglion cell-inner plexiform layer thicknesses in inferior and superiortemporal
      quadrants were significantly lower in the obese group. BMI SDS, insulin, HOMA-IR
      and triglyceride levels were negatively correlated with RNFL thickness,
      significantly (r = -0.386, p < 0.001; r = -0.229, p = 0.002; r = -0.188, p =
      0.013; and r = -0.301, p = 0.000; respectively) in all subjects. CONCLUSIONS:
      Thinning in RNFL was detected in normal-looking discs of obese children, and this
      thinning negatively correlated with BMI SDS. Further studies including large
      series are needed to clarify whether obesity has an effect on RNFL thickness.

PMID- 27718082
TI  - Concentration of Glial Cell Line-Derived Neurotrophic Factor Positively
      Correlates with Symptoms in Functional Dyspepsia.
AB  - BACKGROUND: In patients with functional dyspepsia (FD), mild duodenal
      inflammation correlates with increased mucosal permeability. Enteric glial cells
      can produce glial cell line-derived neurotrophic factor (GDNF) to repair
      disrupted epithelial barrier function. AIMS: We examined the role of duodenal
      GDNF in FD pathophysiology and its association with dyspeptic symptoms. METHODS:
      Duodenal biopsies taken from FD patients and control subjects were used for
      analysis. GDNF protein expression and localization were examined. Cellular
      infiltration of eosinophils and mast cells was measured. We also examined the
      intercellular space between the adjacent epithelial cells at the apical junction
      complex using transmission electron microscopy. RESULTS: In FD patients,
      expression of GDNF protein was significantly increased compared with controls,
      107.3 (95.3-136.7) versus 49.3 (38.0-72.6) pg/mg protein (median (interquartile
      range), p = 0.006), respectively. GDNF was localized in enteric glial cells,
      eosinophils, and epithelial cells. The number of eosinophils was significantly
      greater in FD patients than in controls, 1039 (923-1181) versus 553 (479-598)
      cells/mm2 (p = 0.021), respectively. The intercellular space was dilated at the
      adherent junction in FD patients compared to control patients, 32.4 (29.8-34.8)
      versus 22.0 (19.9-26.1) nm (p = 0.002), respectively. Intercellular distance
      positively correlated with the frequency of postprandial fullness and early
      satiation (p = 0.001, r = 0.837 and p = 0.009, r = 0.693, respectively).
      Expression of GDNF correlated with epigastric burning (p = 0.041, r = 0.552).
      CONCLUSIONS: Increased expression of duodenal GDNF might be involved in FD
      pathophysiology and symptom perception.

PMID- 27718083
TI  - Intestinal Lipomatosis and Chemotherapy: A Growing Concern.

PMID- 27718085
TI  - Hypogammaglobulinemia in infants receiving chronic peritoneal dialysis.
AB  - BACKGROUND: Peritonitis is a severe complication of chronic peritoneal dialysis
      (CPD) in infants. Few studies have been conducted to evaluate the relationship
      between hypogammaglobulinemia and peritonitis risk, and the potential benefit of
      intravenous immunoglobulins (IVIG) therapy in infants receiving CPD. METHODS:
      Patients aged 0-12 months at initiation of CPD between 1985 and 2012 were
      eligible for inclusion in this retrospective study. Data collected from the start
      of CPD up to 2 years post-dialysis initiation included patient demographics,
      dialysis characteristics, serum immunoglobulin (IgG) levels, IVIG administration
      history, infectious complications and outcomes. Cox regression analysis and
      linear mixed model analysis were used for statistical analysis. RESULTS: Twenty
      six consecutive patients were included in the study. Annualized peritonitis rates
      for infants aged 0-30 days (<=1-month age group; n = 16; 320.3 patient-months)
      and 31-365 days (>1-12-month age group; n = 10; 163.3 patient-months) at dialysis
      initiation were 0.27 (1 episode per 45.8 patient-months) and 0.15 (one episode
      per 81.7 patient-months), respectively. Seventy-six percent of the serum IgG
      levels were >1 standard deviation below the age-appropriate mean levels, and
      these did not differ in those who developed peritonitis versus those who did not
      (p = 0.39). Serum IgG levels were significantly lower in patients on CPD with
      oligoanuria than in non-oliguric patients (p = 0.04) and in patients on CPD for
      >90 days as compared to those who had received CPD for <90 days (p = 0.018). IVIG
      therapy was provided to 20 patients with hypogammaglobulinemia; this high
      prevalence of IVIG usage precluded any drawing of conclusion on the potential
      role of IVIG in the prevention of peritonitis. CONCLUSIONS: Hypogammaglobulinemia
      is a frequent complication of CPD during infancy. In our experience, it was not
      associated with an increased risk for peritonitis.

PMID- 27718084
TI  - Previous aminoglycoside use and acute kidney injury risk in non-critically ill
      children.
AB  - OBJECTIVES: Aminoglycosides (AG) are a group of bactericidal antibiotics with
      nephrotoxic effects that are commonly used in the treatment of hospitialized
      children. We have examined previous AG treatment as a risk factor for acute
      kidney injury (AKI) during current AG treatment. STUDY DESIGN: We performed a
      retrospective cohort study of children ranging in age from 1 month to 18 years
      who were treated with AG between October 2008 and April 2012 at Montreal's
      Children's Hospital. Children for whom no serum creatinine data (SCr) were
      available and those with baseline renal disease were excluded from the analysis.
      Main exposures were prior AG use (number and hours of prior treatments) and time
      since last AG treatment. The main outcome was AKI, defined on the basis of the
      Kidney Disease: Improving Global Outcomes guidelines. Logistic regression was
      used to examine exposure-outcome associations. RESULTS: AG treatments episodes
      with Stage 1, 2, and 3 AKI, respectively, were associated with a median of 98
      [interquartile range (IQR) 339], 231 (IQR 688), and 111 (IQR 505) h of prior AG
      treatment, respectively, versus non-AKI (median 0, IQR 54 h) (p < 0.0001). AKI
      episodes were associated with a mean (+/- standard deviation) of 1.5 +/- 1.8 AG
      treatments in the previous 6 months, versus 0.9 +/- 1.6 AG treatments for non
      AKI. The number of AG-treatment days during the preceding 6 months [adjusted odds
      ratio (adjOR) 1.04, 95 % confidence interval (CI) 1.03-1.06; p < 0.001], younger
      age (adjOR 0.96, 95 % CI 0.93-0.99; p = 0.009), admission to hematology-oncology
      department (adjOR 3.88, 95 % CI 2.17-6.96; p < 0.001), and tobramycin use (adjOR
      1.77, 95 % CI 1.04-3.02; p = 0.04) were independently associated with AKI.
      Episodes with Stage 1 and 2 AKI were associated with fewer days since last
      treatment compared to non-AKI treatment (p < 0.02 and p < 0.005, respectively;
      Mann-Whitney test). CONCLUSIONS: Based on these results, prior AG treatment is a
      risk factor for AKI and should be considered when dosing and monitoring
      hospitalized children being treated with AG.

PMID- 27718051
TI  - Are all people with diabetes and cardiovascular risk factors or microvascular
      complications at very high risk? Findings from the Risk and Prevention Study.
AB  - AIMS: To verify whether it is possible, in people with diabetes mellitus (DM)
      considered at very high cardiovascular (CV) risk, stratify this risk better and
      identify significant modifiable risk factor (including lifestyle habits) to help
      patients and clinicians improve CV prevention. METHODS: People with DM and
      microvascular diseases or one or more CV risk factors (hypertension,
      hyperlipidemia, smoking, poor dietary habits, overweight, physical inactivity)
      included in the Risk and Prevention study were selected. We considered the
      combined endpoint of non-fatal acute myocardial infarction and stroke and CV
      death. A multivariate Cox proportional analysis was carried out to identify
      relevant predictors. We also used the RECPAM method to identify subgroups of
      patients at higher risk. RESULTS: In our study, the rate of major CV events was
      lower than expected (5 % in 5 years). Predictors of CV events were age, male,
      sex, heart failure, previous atherosclerotic disease, atrial fibrillation,
      insulin treatment, high HbA1c, heart rate and other CV diseases while being
      physically active was protective. RECPAM analysis indicated that history of
      atherosclerotic diseases and a low BMI defined worse prognosis (HR 4.51 95 % CI
      3.04-6.69). Among subjects with no previous atherosclerotic disease, men with
      HbA1c more than 8 % were at higher CV risk (HR 2.77; 95 % CI 1.86-4.14) with
      respect to women. CONCLUSIONS: In this population, the rate of major CV events
      was lower than expected. This prediction model could help clinicians identify
      people with DM at higher CV risk and support them in achieving goals of physical
      activity and HbA1c.

PMID- 27718087
TI  - When is biopsy-proven TIN not simply TIN? Questions.

PMID- 27718086
TI  - Serological and genetic complement alterations in infection-induced and
      complement-mediated hemolytic uremic syndrome.
AB  - BACKGROUND: The role of complement in the atypical form of hemolytic uremic
      syndrome (aHUS) has been investigated extensively in recent years. As the HUS
      associated bacteria Shiga-toxin-producing Escherichia coli (STEC) can evade the
      complement system, we hypothesized that complement dysregulation is also
      important in infection-induced HUS. METHODS: Serological profiles (C3, FH, FI, AP
      activity, C3d, C3bBbP, C3b/c, TCC, alphaFH) and genetic profiles (CFH, CFI, CD46,
      CFB, C3) of the alternative complement pathway were prospectively determined in
      the acute and convalescent phase of disease in children newly diagnosed with STEC
      HUS or aHUS. Serological profiles were compared with those of 90 age-matched
      controls. RESULTS: Thirty-seven patients were studied (26 STEC-HUS, 11 aHUS). In
      39 % of them, including 28 % of STEC-HUS patients, we identified a genetic and/or
      acquired complement abnormality. In all patient groups, the levels of
      investigated alternative pathway (AP) activation markers were elevated in the
      acute phase and normalized in remission. The levels were significantly higher in
      aHUS than in STEC-HUS patients. CONCLUSIONS: In both infection-induced HUS and
      aHUS patients, complement is activated in the acute phase of the disease but not
      during remission. The C3d/C3 ratio displayed the best discrepancy between acute
      and convalescent phase and between STEC-HUS and aHUS and might therefore be used
      as a biomarker in disease diagnosis and monitoring. The presence of aberrations
      in the alternative complement pathway in STEC-HUS patients was remarkable, as
      well.

PMID- 27718088
TI  - When is biopsy-proven TIN not simply TIN? Answers.

PMID- 27718089
TI  - The relationship between solvent use and BTEX concentrations in occupational
      environments.
AB  - Indoor air quality is an increasing concern; it causes significant damage to
      health because it is recycled in confined environments for extended periods of
      time. Among the pollutants found in these environments, benzene, toluene,
      ethylbenzene, and xylenes (BTEX) are known for their potential toxic, mutagenic,
      and carcinogenic effects. This study monitored the BTEX concentrations in paint,
      carpentry, and varnish workplaces and evaluated the potential to cause adverse
      health effects on workers in these environments. Twenty samples were collected in
      workplaces, 20 samples were collected outside the area, and eight samples were
      taken of the products used. Samples were collected using coconut shell
      cartridges, and chemical analyses were performed by gas chromatography with mass
      spectrometry. Toluene presented higher indoor concentrations and indoor and
      outdoor ratios, indicating that the paint and varnish workplaces had significant
      BTEX sources. The highest benzene and toluene concentrations were obtained from
      the paint workshop, and higher concentrations of ethylbenzene and xylenes were
      obtained in the varnish workshop. The highest non-carcinogenic risks were
      obtained for m + p-xylenes in the varnish work place, and the second highest non
      carcinogenic risk was also determined for the same workshop.

PMID- 27718091
TI  - In Silico and In Vivo Experiments Reveal M-CSF Injections Accelerate Regeneration
      Following Muscle Laceration.
AB  - Numerous studies have pharmacologically modulated the muscle milieu in the hopes
      of promoting muscle regeneration; however, the timing and duration of these
      interventions are difficult to determine. This study utilized a combination of in
      silico and in vivo experiments to investigate how inflammation manipulation
      improves muscle recovery following injury. First, we measured macrophage
      populations following laceration injury in the rat tibialis anterior (TA). Then
      we calibrated an agent-based model (ABM) of muscle injury to mimic the observed
      inflammation profiles. The calibrated ABM was used to simulate macrophage and
      satellite stem cell (SC) dynamics, and suggested that delivering macrophage
      colony stimulating factor (M-CSF) prior to injury would promote SC-mediated
      injury recovery. Next, we performed an experiment wherein 1 day prior to injury,
      we injected M-CSF into the rat TA muscle. M-CSF increased the number of
      macrophages during the first 4 days post-injury. Furthermore, treated muscles
      experienced a swifter increase in the appearance of PAX7+ SCs and regenerating
      muscle fibers. Our study suggests that computational models of muscle injury
      provide novel insights into cellular dynamics during regeneration, and further,
      that pharmacologically altering inflammation dynamics prior to injury can
      accelerate the muscle regeneration process.

PMID- 27718092
TI  - White-Tailed Deer as an Ex Vivo Knee Model: Joint Morphometry and ACL Rupture
      Strength.
AB  - Animal joints are valuable proxies for those of humans in biomechanical studies,
      however commonly used quadruped knees differ greatly from human knees in scale
      and morphometry. To test the suitability of the cervine stifle joint (deer knee)
      as a laboratory model, gross morphometry, ACL cross section, and ACL rupture
      strength were measured and compared to values previously reported for the knees
      of humans and commonly studied animals. Twelve knee joints from wild white-tailed
      deer were tested. Several morphometry parameters, including bicondylar width
      (53.5 +/- 3.0 mm) and notch width (14.7 +/- 2.5 mm), showed a high degree of
      similarity to those of the human knee, while both medial (16.7 +/- 2.1 degrees )
      and lateral (17.6 +/- 4.7 degrees ) tibial slopes were steeper than in humans but
      less steep than other quadrupeds. The median ACL rupture force (2054 N, 95% CI
      2017-2256 N), mean stiffness (260 +/- 166 N/mm), mean length (33 +/- 7 mm), and
      mean cross sectional area (44.8 +/- 18.3 mm2) were also comparable to previously
      reported values for human knees. In our limited sample size, no significant
      sexual dimorphism in strength or morphometry was observed (p >= 0.05 for all
      parameters), though female specimens generally had steeper tibial slopes
      (lateral: p = 0.52, medial: p = 0.07). Our results suggest that the deer knee may
      be a suitable model for ex vivo studies of ACL rupture and repair.

PMID- 27718090
TI  - A comparative study of occurrence and fate of endocrine disruptors: diethyl
      phthalate and dibutyl phthalate in ASP- and SBR-based wastewater treatment
      plants.
AB  - Phthalates are endocrine-disrupting chemicals which affect endocrine system by
      bio-accumulation in aquatic organisms and produce adverse health effects in
      aquatic organisms as well as human beings, when come in contact. Present study
      focuses on occurrence and removal of two phthalates: diethylphthalate (DEP) and
      dibutylphthalate (DBP) in two full-scale wastewater treatment plants (WWTPs) i.e.
      sewage treatment plants (STPs) based on well-adopted technologies, activated
      sludge process (ASP) and sequencing batch reactor (SBR).Gas chromatography-mass
      spectrometry (GC-MS) analysis was performed for both wastewater and sludge sample
      for determination and identification of the concentration of these compounds in
      both STPs by monitoring the STPs for 9 months. It was observed that the
      concentration of DEP was less than DBP in the influent of ASP and SBR. Average
      concentrations of DEP and DBP in sludge sample of ASP were found to be 2.15 and
      2.08 ng/g, whereas in SBR plant, these values were observed as 1.71 and 2.01
      ng/g, respectively. Concerning the removal efficiency of DEP, SBR and ASP plants
      were found effective with removal efficiency of 91.51 and 91.03 %, respectively.
      However, in the case of DBP, SBR showed lower removal efficiency (85.42 %) as
      compared to ASP (92.67 %). Comparative study of both plants proposed that in ASP
      plant, DBP reduction was higher than the SBR. Fourier transformation infrared
      (FTIR) analysis also confirmed the same result of sludge analysis for both STPs.
      Sludge disposal studied with scanning electron microscopy (SEM), energy
      dispersive X-ray spectroscopy (EDX) and thermo-gravimetric analysis (TGA)
      techniques confirmed that sludge of both STPs have high calorific value and can
      be used as fuel to make fuel-briquettes and bottom ash to make firebricks.

PMID- 27718093
TI  - Differential Regulation of Hippocampal IGF-1-Associated Signaling Proteins by
      Dietary Restriction in Aging Mouse.
AB  - Time-dependent alterations in several biological processes of an organism may be
      characterized as aging. One of the effects of aging is the decline in cognitive
      functions. Dietary restriction (DR), an intervention where the consumption of
      food is lessened but without malnutrition, is a well-established mechanism that
      has a wide range of important outcomes including improved health span, delayed
      aging, and extension of lifespan of various species. It also plays a beneficial
      role in protecting against age-dependent deterioration of cognitive functions,
      and has neuroprotective properties against neurodegenerative diseases. Insulin
      like growth factor (IGF)-1 plays an important role in the regulation of cellular
      and tissue functions, and relating to the aging process the most important
      pathway of IGF-1 is the phosphatidylinositol 3-kinase (PI3K) and protein kinase B
      (Akt/PKB) signaling cascade. Although many have studied the changes in the level
      of IGF-1 and its effect on neural proliferation, the downstream signaling
      proteins have not been fully elucidated. Hence in the present investigation, the
      IGF-1 gene expression and the normal endogenous levels of IGF1R (IGF-1 receptor),
      PI3K, Akt, pAkt, and pFoxO in the hippocampus of young, adult, and old mice were
      determined using real-time PCR and Western blot analyses. The effects of DR on
      these protein levels were also studied. Results showed a decrease in the levels
      of IGF-1, IGF1R, PI3K, and pAkt, while pFoxO level increased with respect to age.
      Under DR, these protein levels are maintained in adult mice, but old mice
      displayed diminished expression levels of these proteins as compared to ad
      libitum-fed mice. Maintenance of PI3K/Akt pathway results in the phosphorylation
      of FoxOs, necessary for the enhancement of neural proliferation and survival in
      adult mice. The down-regulation of IGF-I signaling, as observed in old mice,
      leads to increasing the activity of FoxO factors that may be important for the
      neuroprotective effects seen with DR.

PMID- 27718094
TI  - DasR positively controls monensin production at two-level regulation in
      Streptomyces cinnamonensis.
AB  - The polyether ionophore antibiotic monensin is produced by Streptomyces
      cinnamonensis and is used as a coccidiostat for chickens and growth-promoting
      agent for cattle. Monensin biosynthetic gene cluster has been cloned and
      partially characterized. The GntR-family transcription factor DasR regulates
      antibiotic production and morphological development in Streptomyces coelicolor
      and Saccharopolyspora erythraea. In this study, we identified and characterized
      the two-level regulatory cascade of DasR to monensin production in S.
      cinnamonensis. Forward and reverse genetics by overexpression and antisense RNA
      silence of dasR revealed that DasR positively controls monensin production under
      nutrient-rich condition. Electrophoresis mobility shift assay (EMSA) showed that
      DasR protein specifically binds to the promoter regions of both pathway-specific
      regulatory gene monRII and biosynthetic genes monAIX, monE and monT. Semi
      quantitative RT-PCR further confirmed that DasR upregulates the transcriptional
      levels of these genes during monensin fermentation. Subsequently, co
      overexpressed dasR with pathway-specific regulatory genes monRI, monRII or monH
      greatly improved monensin production.

PMID- 27718097
TI  - Erratum to: Analysis of Relations Between the Level of Mg, Zn, Ca, Cu, and Fe and
      Depressiveness in Postmenopausal Women.

PMID- 27718096
TI  - TAZ Activator Is Involved in IL-10-Mediated Muscle Responses in an Animal Model
      of Traumatic Brain Injury.
AB  - The transcriptional coactivator with PDZ-binding motif (TAZ) functions as a
      downstream regulatory target in the Hippo signaling pathway that plays various
      roles. We previously developed a cell-based assay and identified the TAZ
      activator IBS008738 as a potential therapeutic target for glucocorticoid-induced
      atrophy. To further explore the application of IBS008738 in various muscle
      related diseases, we examined the function of IBS008738 in inflammatory cytokine
      mediated mouse muscle responses after traumatic brain injury (TBI). Preliminary
      screening suggested that IBS008738 treatments increased the levels of IL-10 in
      C2C12 cells. In TBI and sham control mice, we compared the effect of IBS008738
      treatments on TNF alpha, IL-6, and IL-10 mRNA levels, muscle morphologic changes,
      and macrophage phenotype changes. Our findings support that the TAZ activator
      IBS008738 decreases muscle wasting by upregulating IL-10 and inhibiting TNF alpha
      and IL-6, and this process is implemented by changing the macrophage phenotypes.
      These results indicate a new mechanism of the TAZ activator as a potential
      therapy for atrophy.

PMID- 27718095
TI  - Indirubin Inhibits LPS-Induced Inflammation via TLR4 Abrogation Mediated by the
      NF-kB and MAPK Signaling Pathways.
AB  - Indirubin plays an important role in the treatment of many chronic diseases and
      exhibits strong anti-inflammatory activity. However, the molecular mode of action
      during mastitis prophylaxis remains poorly understood. In this study, a
      lipopolysaccharide (LPS)-induced mastitis mouse model showed that indirubin
      attenuated histopathological changes in the mammary gland, local tissue necrosis,
      and neutrophil infiltration. Moreover, indirubin significantly downregulated the
      production of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF
      alpha). We explored the mechanism whereby indirubin exerts protective effects
      against LPS-induced inflammation of mouse mammary epithelial cells (MMECs). The
      addition of different concentrations of indirubin before exposure of cells to LPS
      for 1 h significantly attenuated inflammation and reduced the concentrations of
      the three inflammatory cytokines in a dose-dependent manner. Indirubin
      downregulated LPS-induced cyclooxygenase-2 (COX-2) and Toll-like receptor 4
      (TLR4) expression, inhibited phosphorylation of the LPS-induced nuclear
      transcription factor-kappa B (NF-kB) P65 protein and its inhibitor IkBalpha of
      the NF-kB signaling pathway. Furthermore, indirubin suppressed phosphorylation of
      P38, extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase
      (JNK) of the mitogen-activated protein kinase (MAPK) signal pathways. Thus,
      indirubin effectively suppressed LPS-induced inflammation via TLR4 abrogation
      mediated by the NF-kB and MAPK signaling pathways and may be useful for mastitis
      prophylaxis.

PMID- 27718099
TI  - Bayesian Modelling of Induced Responses and Neuronal Rhythms.
AB  - Neural rhythms or oscillations are ubiquitous in neuroimaging data. These
      spectral responses have been linked to several cognitive processes; including
      working memory, attention, perceptual binding and neuronal coordination. In this
      paper, we show how Bayesian methods can be used to finesse the ill-posed problem
      of reconstructing-and explaining-oscillatory responses. We offer an overview of
      recent developments in this field, focusing on (i) the use of MEG data and
      Empirical Bayes to build hierarchical models for group analyses-and the
      identification of important sources of inter-subject variability and (ii) the
      construction of novel dynamic causal models of intralaminar recordings to explain
      layer-specific activity. We hope to show that electrophysiological measurements
      contain much more spatial information than is often thought: on the one hand, the
      dynamic causal modelling of non-invasive (low spatial resolution)
      electrophysiology can afford sub-millimetre (hyper-acute) resolution that is
      limited only by the (spatial) complexity of the underlying (dynamic causal)
      forward model. On the other hand, invasive microelectrode recordings (that
      penetrate different cortical layers) can reveal laminar-specific responses and
      elucidate hierarchical message passing and information processing within and
      between cortical regions at a macroscopic scale. In short, the careful and
      biophysically grounded modelling of sparse data enables one to characterise the
      neuronal architectures generating oscillations in a remarkable detail.

PMID- 27718098
TI  - Neurovascular emergencies: imaging diagnosis and neurointerventional treatment.
AB  - Neurovascular emergencies, consisting of acute ischemic stroke, non-traumatic
      aneurysmal subarachnoid hemorrhage, arteriovenous malformation, dural
      arteriovenous fistula, and carotid- cavernous fistula, can have an acute
      presentation to the emergency department. Radiologists should have an
      understanding of these processes and their imaging findings in order to provide a
      prompt and accurate diagnosis. Neurointerventional radiology plays a critical
      role in providing additional diagnostic information and potentially curative
      treatment. Understanding the grading scales used to evaluate and prognosticate
      these neurovascular emergencies can help expedite management for best possible
      patient outcomes.

PMID- 27718100
TI  - Erratum to: A prospective randomized multicenter phase I/II clinical trial to
      evaluate safety and efficacy of NOVOCART disk plus autologous disk chondrocyte
      transplantation in the treatment of nucleotomized and degenerative lumbar disks
      to avoid secondary disease: safety results of Phase I-a short report.

PMID- 27718101
TI  - Erratum to: Mitochondrial CHCHD-Containing Proteins: Physiologic Functions and
      Link with Neurodegenerative Diseases.

PMID- 27718102
TI  - Erratum to: Local Interleukin-18 System in the Basolateral Amygdala Regulates
      Susceptibility to Chronic Stress.

PMID- 27718103
TI  - Aberrant Axonal Arborization of PDF Neurons Induced by Abeta42-Mediated JNK
      Activation Underlies Sleep Disturbance in an Alzheimer's Model.
AB  - Impaired sleep patterns are common symptoms of Alzheimer's disease (AD). Cellular
      mechanisms underlying sleep disturbance in AD remain largely unknown. Here, using
      a Drosophila Abeta42 AD model, we show that Abeta42 markedly decreases sleep in a
      large population, which is accompanied with postdevelopmental axonal arborization
      of wake-promoting pigment-dispersing factor (PDF) neurons. The arborization is
      mediated in part via JNK activation and can be reversed by decreasing JNK
      signaling activity. Axonal arborization and impaired sleep are correlated in
      Abeta42 and JNK kinase hemipterous mutant flies. Image reconstruction revealed
      that these aberrant fibers preferentially project to pars intercerebralis (PI), a
      fly brain region analogous to the mammalian hypothalamus. Moreover, PDF signaling
      in PI neurons was found to modulate sleep/wake activities, suggesting that
      excessive release of PDF by these aberrant fibers may lead to the impaired sleep
      in Abeta42 flies. Finally, inhibition of JNK activation in Abeta42 flies restores
      nighttime sleep loss, decreases Abeta42 accumulation, and attenuates
      neurodegeneration. These data provide a new mechanism by which sleep disturbance
      could be induced by Abeta42 burden, a key initiator of a complex pathogenic
      cascade in AD.

PMID- 27718104
TI  - The Family Socialization Interview-Revised (FSI-R): a Comprehensive Assessment of
      Parental Disciplinary Behaviors.
AB  - Elucidating the complex mechanisms by which harsh parenting increases risk of
      child psychopathology is key to targeted prevention. This requires nuanced
      methods that capture the varied perceptions and experiences of diverse families.
      The Family Socialization Interview-Revised (FSI-R), adapted from an interview
      developed by Dodge et al. (Child Development, 65, 649-665, 1994), is a
      comprehensive, semi-structured interview for characterizing methods of parental
      discipline used with young children. The FSI-R coding system systematically rates
      parenting style, usual discipline techniques, and most intense physical and
      psychological discipline based on rater judgment across two eras: (1) birth to
      the previous year, and (2) the previous year to present. The current study
      examined the psychometric properties of the FSI-R in a diverse, high-risk
      community sample of 386 mothers and their children, ages 3 to 6 years. Interrater
      reliability was good to excellent for codes capturing physically and
      psychologically harsh parenting, and restrictive/punitive parenting styles.
      Findings supported the FSI-R's convergent and incremental validity. Importantly,
      the FSI-R demonstrated incremental utility, explaining unique variance in
      children's externalizing and internalizing symptoms beyond that explained by
      traditional surveys and observed parenting. The FSI-R appeared particularly
      promising for capturing risk associated with young children's depressive
      symptoms, as these were generally not significantly associated with other
      measures of harsh parenting. Overall, findings support the added value of the FSI
      R within a multi-method assessment of disciplinary practices across early child
      development. Future implications for prevention are discussed.

PMID- 27718105
TI  - Bruises in beef cattle at slaughter in Mexico: implications on quality, safety
      and shelf life of the meat.
AB  - In emergent economies and developing countries of Africa, Asia and Latin America,
      the major cause for carcass rejection from the international market is bruising;
      nevertheless, many of these carcases are destined to local markets and meat
      processing industries for human consumption. Therefore, the aim of the present
      study was to assess the effect of bruised meat on pH, microbiologic count and
      biogenic amine (BA) profiles along 21 days of ageing (sampling 1st, 7th, 14th and
      21st day) with two packaging method (plastic bag vs vacuum) at 4  degrees C. A
      total of 50 bruised carcasses were sampled from 1000 young bulls (Brown Swiss X
      Zebu) of 18-24 months old and an average live weight of 450 +/- 66 kg. The
      results showed significant differences between packaging systems and bruised vs
      non-bruised meat. The bruised meat caused higher biogenic amine concentrations
      than did non-bruised meat. We conclude that bruised meat favoured increments of
      biogenic amine concentrations, even more than did non-bruised meat. The plastic
      bag + vacuum system limited the increments of BA concentration during storage
      time therefore it improved shelf life of meat. These results emphasized the
      importance of implementing best management practices during pre-slaughter
      operations of cattle in order to reduce a possible risk factor for bruised meat.

PMID- 27718106
TI  - Challenges for beef production in smallholder communities with low reproductive
      management skills: a case study from Northern Lao PDR.
AB  - Improved large ruminant productivity is increasingly acknowledged as a pathway
      for the alleviation of rural poverty and food insecurity in smallholder
      communities in Southeast Asia; yet, in much of Laos, bovine reproductive
      management is practically absent. Large ruminant reproduction skills were
      studied, using face-to-face surveys (n=60) of the knowledge, attitudes, and
      practices (KAP) of farmers, plus an extension of an examination of parameters of
      reproductive efficiency (n = 1786 cattle and 434 buffalo) in the northern
      provinces of Luang Prabang and Xieng Khouang. The surveys particularly involved
      female farmers to provide gender-disaggregated data, with females making up 38.3
      % of participants. Results confirmed that KAPs of smallholder farmers on bovine
      reproductive management were low (34-46 %) with trends toward higher KAP scores
      in male survey respondents. Poor reproductive parameters were identified in both
      provinces, with low calving percentages of 54-75 and 45-54 % in cattle and
      buffalo groups, respectively, and prolonged inter-calving intervals of 14.1-19.8
      and 26.0 months for the cattle and buffalo groups, respectively. Improving the
      reproductive efficiency of large ruminants in the northern upland regions would
      enable smallholder farmers to be more effectively engaged in the dramatic
      economic growth of the Southeast Asia region, although these findings indicate
      that intensive training and supportive interventions are required to improve
      large ruminant reproductive outcomes in communities that have low-level large
      ruminant husbandry skills.

PMID- 27718107
TI  - Nutraceutic effect of free condensed tannins of Lysiloma acapulcensis (Kunth)
      benth on parasite infection and performance of Pelibuey sheep.
AB  - Forty-five Pelibuey sheep were experimentally infested with nematodes to evaluate
      the effect of three free condensed tannin (FCT) levels of Lysiloma acapulcensis
      on fecal egg counts (FECs), packed cell volumes (PCV), ocular mucosa colors
      (OMC), average daily gain (ADG), and adult nematode count. Five treatments were
      used: 12.5, 25.0, and 37.5 mg of FCT kg-1 of body weight (BW); sterile water
      (control); and ivermectine (0.22 mg kg-1 of BW) as chemical group. The data were
      processed through repeated measurement analysis. Even though the three FCT doses
      decreased (P < 0.05) the FEC, the highest reduction was obtained with 37.5 mg kg
      1 of BW. No differences were observed in PCV and OMC. Higher ADG (P < 0.05) was
      observed with 37.5 mg kg-1 of BW of FCT. The count of adult nematodes (females
      and males) in the higher dose of FCT was similar to chemical treatment. Dose of
      37.5 mg kg-1 of BW decreased the parasite infection and improved the lamb
      performance. Therefore, this dose could be used as a nutraceutic product in sheep
      production.

PMID- 27718108
TI  - Effect of dried rumen digesta pellet levels on feed use, rumen ecology, and blood
      metabolite in swamp buffalo.
AB  - The aim of this experiment was to determine the effect of dried rumen digesta
      pellet levels on feed intake, digestibility, rumen ecology, and blood metabolites
      in swamp buffalo. Four 2-year-old male swamp buffalo with an initial body weight
      (BW) of 150 +/- 10.0 kg were randomly assigned according to a 4 * 4 Latin square
      design to receive four levels of dried rumen digesta pellets (DRDPs). The dietary
      treatments were supplementation of DRDP at 0, 50, 100, and 150 g dry matter/day,
      respectively. Total feed intake was significantly different among treatments (p <
      0.05) and was highest in the 150 g/day DRDP supplement (2.68 kg/day). Intakes of
      neutral detergent fiber (NDF) and acid detergent fiber did not affect DRDP
      levels, while intakes of organic matter and crude protein (CP) were altered
      significantly when 150 g of DRDP was used (p < 0.05). Buffalo fed with DRDP at
      150 g/day had the highest CP and NDF digestibility (p < 0.05). DRDP
      supplementation did not affect rumen pH, and temperature and the concentration of
      ruminal ammonia-nitrogen and blood urea nitrogen were not altered among the
      treatments. The mean value of fungal zoospores in the buffalo was significantly
      different among treatments and was highest in supplementation with DRDP at 150 g.
      The mean value of propionic acid was significantly different at various levels of
      DRDP; it was highest in the group fed with 150 g DRDP (p < 0.05). Thus,
      supplementation of DRDP at 150 g improved feed use and increased fungal zoospore
      population. In addition, DRDP feeding is recommended, since it has positive
      economic impacts and helps control environmental pollution.

PMID- 27718109
TI  - Spineless cactus as a replacement for sugarcane in the diets of finishing lambs.
AB  - The effects of replacement of sugarcane by spineless cactus (0, 33, 66, and 100 %
      on dry matter (DM) basis) were evaluated on intake, digestibility of nutrients,
      ingestive behavior, and performance of finishing lambs. Thirty-six non-castrated
      Santa Ines lambs at 4 months of age and an initial body weight of 22 +/- 2.3 kg
      were assigned in a randomized block design. A quadratic effect was found for
      intake of DM, organic matter (OM), crude protein (CP), neutral detergent fiber
      (NDF), and digestible organic matter (DOM), with maximum values of 1.31, 1.19,
      0.219, 0.358, and 0.845 g/day estimated with 42.5, 38.5, 38.8, 21.3, and 44.9 %
      replacement level, respectively. The digestibility of DM, OM, CP, and EE
      increased linearly; however, there was a quadratic effect on NDF digestibility
      with maximum value estimated of 500 g/kg with 64.2 % replacement level.
      Rumination time, total chewing, and rumination efficiency decreased linearly with
      the replacement levels; however, idle time increased linearly. A quadratic effect
      was found for final weight, body weight gain, and total weight gain with maximum
      values estimated of 38.6 kg, 0.232 kg/day, and 16.2 kg with 39.1, 38.2, and 40.4
      % replacing levels. The replacement of 49.5 % sugarcane by spineless cactus can
      be recommended as optimal level, and problems related to intake, digestibility,
      and performance are concentrated outside that level.

PMID- 27718111
TI  - Prediction of municipal solid waste generation using artificial neural network
      approach enhanced by structural break analysis.
AB  - This paper presents the development of a general regression neural network (GRNN)
      model for the prediction of annual municipal solid waste (MSW) generation at the
      national level for 44 countries of different size, population and economic
      development level. Proper modelling of MSW generation is essential for the
      planning of MSW management system as well as for the simulation of various
      environmental impact scenarios. The main objective of this work was to examine
      the potential influence of economy crisis (global or local) on the forecast of
      MSW generation obtained by the GRNN model. The existence of the so-called
      structural breaks that occur because of the economic crisis in the studied period
      (2000-2012) for each country was determined and confirmed using the Chow test and
      Quandt-Andrews test. Two GRNN models, one which did not take into account the
      influence of the economic crisis (GRNN) and another one which did (SB-GRNN), were
      developed. The novelty of the applied method is that it uses broadly available
      social, economic and demographic indicators and indicators of sustainability,
      together with GRNN and structural break testing for the prediction of MSW
      generation at the national level. The obtained results demonstrate that the SB
      GRNN model provide more accurate predictions than the model which neglected
      structural breaks, with a mean absolute percentage error (MAPE) of 4.0 % compared
      to 6.7 % generated by the GRNN model. The proposed model enhanced with structural
      breaks can be a viable alternative for a more accurate prediction of MSW
      generation at the national level, especially for developing countries for which a
      lack of MSW data is notable.

PMID- 27718110
TI  - HIV-1-derived single-stranded RNA acts as activator of human neutrophils.
AB  - Neutrophils are key effector cells of the innate immune system and are involved
      in the host defense against invading pathogens such as viruses. Recently, it was
      reported that HIV-1-neutrophil interaction triggers neutrophil activation and
      promotes expression of Toll-like receptors (TLRs). Here, we assessed the role of
      single-stranded RNA40 (ssRNA40) derived from HIV-1 in neutrophil activation. We
      observed functional activation of neutrophils in response to HIV-1-derived
      ssRNA40 based on the expression of TLR7/8, RIG-I, and MDA5, induction of
      cytokines (IL-6 and TNF-alpha), and the production of reactive oxygen species
      (ROS). Additionally, ssRNA40 promoted the expression of CD62L and TNF-alpha and
      the production of ROS in the presence of the TLR2 agonist Pam2CSK4. ssRNA40
      together with R848 (a TLR7/8 agonist) increased CD11b expression but decreased
      CD62L expression. Furthermore, decreased IL-6 expression was observed in the
      presence of the TLR4 agonist LPS. Finally, we found that ssRNA40 promotes RIG-I
      and MDA5 expression in the presence of the TLR2, TLR4 and TLR7/8 agonists. This
      study demonstrates a functional response of TLRs in neutrophils challenged with
      ssRNA40, suggesting that TLRs could be involved in the innate immune response
      observed during HIV infection, which might be mediated by its genome.

PMID- 27718113
TI  - Application of electrochemical processes to membrane bioreactors for improving
      nutrient removal and fouling control.
AB  - Membrane bioreactor (MBR) technology is becoming increasingly popular as
      wastewater treatment due to the unique advantages it offers. However, membrane
      fouling is being given a great deal of attention so as to improve the performance
      of this type of technology. Recent studies have proven that the application of
      electrochemical processes to MBR represents a promising technological approach
      for membrane fouling control. In this work, two intermittent voltage gradients of
      1 and 3 V/cm were applied between two cylindrical perforated electrodes, immersed
      around a membrane module, at laboratory scale with the aim of investigating the
      treatment performance and membrane fouling formation. For comparison purposes,
      the reactor also operated as a conventional MBR. Mechanisms of nutrient removal
      were studied and membrane fouling formation evaluated in terms of transmembrane
      pressure variation over time and sludge relative hydrophobicity. Furthermore, the
      impact of electrochemical processes on transparent exopolymeric particles (TEP),
      proposed as a new membrane fouling precursor, was investigated in addition to
      conventional fouling precursors such as bound extracellular polymeric substances
      (bEPS) and soluble microbial products (SMP). All the results indicate that the
      integration of electrochemical processes into a MBR has the advantage of
      improving the treatment performance especially in terms of nutrient removal, with
      an enhancement of orthophosphate (PO4-P) and ammonia nitrogen (NH4-N) removal
      efficiencies up to 96.06 and 69.34 %, respectively. A reduction of membrane
      fouling was also observed with an increase of floc hydrophobicity to 71.72 %, a
      decrease of membrane fouling precursor concentrations, and, thus, of membrane
      fouling rates up to 54.33 %. The relationship found between TEP concentration and
      membrane fouling rate after the application of electrochemical processes confirms
      the applicability of this parameter as a new membrane fouling indicator.

PMID- 27718112
TI  - Lifetime cancer risk assessment for inhalation exposure to di(2-ethylhexyl)
      phthalate (DEHP).
AB  - The plasticizer di(2-ethylhexyl) phthalate (DEHP) is ubiquitous in the
      environment and considered as carcinogen; however, the carcinogenic risk of human
      exposure to DEHP in the air via inhalation is lacking. A probabilistic
      incremental lifetime cancer risk (ILCR) model was implemented to quantitatively
      estimate the potential cancer risk of DEHP via human inhalation by using Monte
      Carlo simulation. We assessed the cancer risk in different age groups (children,
      adolescents, and adults) exposed to different DEHP concentrations (background
      low, indoor moderate, and occupational high) for different durations (2, 8, and
      20 years). Results showed that the cancer risk of exposure to DEHP was below the
      acceptable limit (10-6) in the ambient air but was serious in indoor and
      occupational environments even at short exposure duration (2 years). The cancer
      risk of DEHP via inhalation in children was lower than that in adolescents and
      adults, but the risk in children via dermal and oral exposure to indoor dust and
      soft PVC toys should be considered. Sensitivity analysis indicated that the
      exposure concentration of DEHP was the strongest factor that influenced ILCR. Our
      work provides the evidence of cancer risk of DEHP via inhalation and highlights
      the risk in indoor and occupational environments.

PMID- 27718114
TI  - A follow-up on the analytical study of discolouration of the marble statues of
      Orsanmichele in Florence.
AB  - The research complements the complex study carried out to understand the source
      of brown discolourations of ten marble statues in the Church of Orsanmichele in
      Florence, Italy. Originally located in exterior niches, the statues were restored
      to reverse the extensive alterations they had undergone throughout the centuries.
      One of the major alterations was the application of a dark brown patina that
      dated just after 1789. After the statues were placed indoors, brownish
      discolourations started to appear on their surfaces. Cross sections were examined
      using FTIR mapping and immunological methods. In parallel, the pyrolysis-gas
      chromatography/mass spectrometry (py-GC/MS) data already obtained from the
      statues' scrapings were compared with data from aged casein films applied to
      microscope glass slides and aged milk-treated marble. All the statues had been
      treated with milk-based substances before the time the bronze patina was applied.
      The values of temperature and illumination of the room were important factors in
      the ageing of organic substances and in the formation of calcium oxalates. It is
      likely that products of thermo-oxidation and photo-oxidation of the oils together
      with the oxalates caused the darkening. The marble samples corresponded to a
      Lunense provenance.

PMID- 27718116
TI  - Assessing of policies and practices for occupational exposure to blood-borne
      viral infections in Tanta University Hospitals, Egypt.
AB  - One of the best ways to investigate and improve the effectiveness of polices for
      prevention and control of infections is through systematic and rigorous
      evaluation of the structural, functional, and practical elements of these
      polices. To assess the policies for managing occupational exposure to blood-borne
      viral infections in Tanta University Hospitals. A cross-sectional survey was
      carried out. A checklist was used to collect data related to the hospital policy
      regarding occupational exposure to blood-borne viral infections which was filled
      by direct personal interviews with the members of infection control (IC)
      committee of Tanta University Hospitals where the percentage of those in
      compliance with specific occupational management policies were reported. All
      studied participants reported lack of access to written infection control manual
      and only 14.3 % reported that infection control policies and procedures are
      updated yearly. Only 32.5 % of studied healthcare workers (HCWs) were not aware
      by the availability of a needle injury clinic. Only 28.6 % of the members of IC
      committee reported that pre-placement screening of HCWs for baseline blood tests
      for HBV, HCV, or HIV was conducted; however, periodic screening for these
      infections was not conducted as reported by all of the members. Among the members
      of IC committee, 57.1 % recorded availability of post-exposure evaluation. Only
      42.8 % of the members of IC committee reported ensuring HCWs' confidentiality
      when reporting their exposure incidents. Both exposure management policies and
      practices were not aligning with the national guidelines.

PMID- 27718115
TI  - Association between inflammation processes, DNA damage, and exposure to
      environmental pollutants.
AB  - Environmental exposure to pollutants, especially polycyclic aromatic hydrocarbons
      (PAHs), could lead to carcinogenesis development. However, there is a gap on the
      mechanisms involved in this effect. Therefore, the aim of this study was to
      investigate the potential relationship between exposure to environmental air
      pollution and inflammation process in DNA damage in taxi drivers. This study
      included 45 taxi drivers and 40 controls; non-smokers composed both groups.
      Biological monitoring was performed through quantification of urinary 1
      hydroxypyrene (1-OHP). ICAM-1 (CD54) expression, NTPDase activity, inflammatory
      cytokine (IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma) levels, and comet and
      micronucleus assays were evaluated. The results demonstrated that 1-OHP levels,
      ICAM-1 expression, NTPDase activity, and DNA damage biomarkers (% tail DNA and
      micronucleus frequency) were increased in taxi drivers compared to the control
      group (p < 0.01). Moreover, significant associations were found between 1-OHP
      levels and ICAM-1 expression, % tail DNA, and micronucleus frequency (p < 0.05).
      Besides, pro-inflammatory cytokine levels were positively correlated to % tail
      DNA and micronucleus frequency (p < 0.001). Our findings suggest an important
      association between environmental exposure to air pollution with increase of ICAM
      1 expression and NTPDase activity in taxi drivers. Additionally, the multiple
      regression linear-analysis demonstrated association between IL-6 and DNA damage.
      Thus, the present study has provided important evidence that, in addition to
      environmental exposure to air pollutants, the inflammation process may contribute
      to DNA damage.

PMID- 27718118
TI  - Assessment of Minimum Inhibitory Concentrations of Telavancin by Revised Broth
      Microdilution Method in Phase 3 Hospital-Acquired Pneumonia/Ventilator-Associated
      Pneumonia Clinical Isolates.
AB  - INTRODUCTION: The broth microdilution method (BMD) for testing telavancin minimum
      inhibitory concentrations (MICs) was revised (rBMD) in 2014 to improve the
      accuracy, precision, and reproducibility of the testing method. The aim of this
      study was to determine the effect of the revised method on telavancin MIC values
      for Staphylococcus aureus (S. aureus) clinical isolates obtained from hospital
      acquired pneumonia (HAP) patients. METHODS: Isolates from patients who
      participated in the phase 3 Assessment of Telavancin for Treatment of HAP Studies
      were retested using the rBMD method. RESULTS: Retesting of 647 isolates produced
      a range of telavancin MIC values from 0.015 ug/mL to 0.12 ug/mL with MIC50/90
      values of 0.06/0.06 ug/mL for the total pool of samples. For methicillin
      resistant S. aureus (MRSA), MIC50/90 values were 0.06/0.12 ug/mL. These values
      are up to 4-fold lower than MIC50/90 values obtained using the original method.
      These results were used in part to justify lowering the telavancin breakpoints.
      All tested isolates remained susceptible to telavancin at the revised
      susceptibility breakpoint of <=0.12 ug/mL. Overall, the clinical cure rate for
      microbiologically evaluable telavancin-treated patients was 78% for S. aureus,
      76% for patients with MRSA, and 79% for patients with isolates with reduced
      susceptibility to vancomycin (MIC >=1 ug/mL). CONCLUSION: Results from the rBMD
      method support the in vitro potency of telavancin against S. aureus. TRIAL
      REGISTRATION: ATTAIN (NCT00107952 and NCT00124020). FUNDING: Theravance Biopharma
      Antibiotics, Inc.

PMID- 27718117
TI  - Overexpression of OsDT11, which encodes a novel cysteine-rich peptide, enhances
      drought tolerance and increases ABA concentration in rice.
AB  - Short-chain peptides play important roles in plant development and responses to
      abiotic and biotic stresses. Here, we characterized a gene of unknown function
      termed OsDT11, which encodes an 88 amino acid short-chain peptide and belongs to
      the cysteine-rich peptide family. It was found that the expression of OsDT11 can
      be activated by polyethylene glycol (PEG) treatment. Compared with wild-type
      lines, the OsDT11-overexpression lines displayed dramatically enhanced tolerance
      to drought and had reduced water loss, reduced stomatal density, and an increased
      the concentration of abscisic acid (ABA). The suppression of OsDT11 expression
      resulted in an increased sensitivity to drought compared to wild-type expression.
      Several drought-related genes, including genes encoding abscisic acid (ABA)
      signaling markers, were also strongly induced in the OsDT11-overexpressing lines.
      Moreover, the expression of OsDT11 was repressed in ABA-insensitive mutant
      Osbzip23 and Os2H16 RNAi lines. These results suggest that OsDT11-mediated
      drought tolerance may be dependent on the ABA signaling pathway.

PMID- 27718119
TI  - Successful colonoscopic fecal microbiota transplantation for active ulcerative
      colitis: First report from India.
AB  - Forty-four-year-old male with ulcerative colitis (UC) for 11 years reported
      frequent relapse despite daily sulfasalazine 4 g, azathioprine 125 mg, and rectal
      5-aminosalicylic acid. Repeated use of corticosteroids led to cataract. At
      enrollment, he was passing eight stools a day with blood with a Mayo score of 9
      (3+1+3+2). Stool was negative for ova/cysts/acid fast bacilli and Clostridium
      difficile toxin assay. Rectal biopsy showed cryptitis, crypt abscess, and crypt
      distortion with no inclusion bodies, and cytomegalovirus DNA was negative.
      Following informed consent and approval from IEC, three sessions of fecal
      microbiota transplant (FMT) were performed at intervals of 2 weeks. The donor was
      a 34-year-old relative with no history of gastrointestinal illness, no use of
      antibiotics over 3 months, and free from transmissible disease as per standard
      protocol. At colonoscopy, 350 mL of blended and filtered donor stool, drawn into
      seven syringes of 50 cm3, was instilled from terminal ileum to sigmoid. Follow up
      sigmoidoscopy and rectal biopsy were done monthly for 6 months. There was
      symptomatic, colonoscopic, and histopathological improvement with the Mayo scores
      of 4.1 and 0 at 4.8 and 12 weeks post FMT. Azathioprine and sulfasalazine were
      tapered sequentially between months 4 and 6 of FMT. He remains in clinical and
      endoscopic remission 8 months after FMT and 2 months after withdrawal of all
      medication. Colonoscopic FMT may be effective in inducing drug-free remission in
      patients with active UC.

PMID- 27718120
TI  - Ceftriaxone-Associated Biliary and Cardiopulmonary Adverse Events in Neonates: A
      Systematic Review of the Literature.
AB  - BACKGROUND: Ceftriaxone is a third-generation cephalosporin with broad-spectrum
      activity against both Gram-positive and Gram-negative bacteria. Despite its
      effectiveness, its use for the treatment of infections in neonatal patients has
      been limited because of concern about its potential toxicity. OBJECTIVE: Our aim
      was to review the literature for an association between ceftriaxone and
      cardiopulmonary events, hyperbilirubinemia, and pseudolithiasis among neonates.
      METHODS: We searched PubMed and EMBASE and included studies that evaluated
      ceftriaxone safety in neonates. Study bias was evaluated in the following
      domains: exposure measurement, outcome measurement, attrition, generalizability,
      confounding, statistical analysis, and reporting. RESULTS: We included nine
      studies regarding ceftriaxone side effects, primarily spontaneous reports,
      published case reports, and small case series. Reports of bilirubin displacement
      attributed to ceftriaxone included increases in serum bilirubin necessitating
      antibiotic change in a subset of infants after administration of ceftriaxone. One
      study described self-resolving biliary sludge after ceftriaxone administration in
      six of 80 infants. Cardiopulmonary adverse events included a report of eight
      cardiopulmonary events related to concomitant ceftriaxone-calcium infusion,
      including seven infant deaths. Additional cardiopulmonary events reported
      included perinatal asphyxia, pulmonary hypertension, and thrombocytosis. However,
      the available literature had small sample sizes, poor external validity, and
      inconsistent outcome ascertainment methods, which made it impossible to estimate
      the magnitude of risk. DISCUSSION: Concomitant administration of intravenous
      ceftriaxone and calcium-containing solutions should be avoided in neonates.
      However, further controlled studies are needed to assess whether bilirubin
      displacement associated with the use of ceftriaxone is clinically relevant,
      particularly in healthy term and near-term neonates with mild hyperbilirubinemia.

PMID- 27718121
TI  - What Are the Risk Factors for Revision Surgery After Hip Arthroscopy for
      Femoroacetabular Impingement at 7-year Followup?
AB  - BACKGROUND: In recent years, surgical treatment of symptomatic femoroacetabular
      impingement (FAI) has been increasingly performed using arthroscopy. Bony
      pathomorphologies and damage to the labrum as well as cartilage defects can be
      addressed with comparable results to open surgery with overall less surgery
      related complications. Despite the increasing importance of hip arthroscopy,
      however, reports on midterm clinical and radiographic outcomes and comparison to
      open surgical hip dislocation are scarce. QUESTIONS/PURPOSES: (1) What are the
      clinical and radiographic outcomes at a mean 7-year followup; (2) what is the
      cumulative 7-year survivorship, using the endpoints of THA, progression of
      osteoarthritis according to Tonnis, or poor clinical outcome with a Merle
      d'Aubigne score of less than 15 points, of hips with symptomatic FAI treated
      arthroscopically; and (3) what factors were associated with revision surgery?
      METHODS: Between 2003 and 2008 we performed a total of 62 arthroscopic procedures
      (60 patients) for FAI. For the same indication, we also performed 571 surgical
      hip dislocations during that time. Standardized treatment was femoral offset
      correction, acetabular rim trimming, or both and treatment of labral or chondral
      defects. An arthroscopic approach was generally used if the pathomorphology was
      located in the anterosuperior quadrant of the hip and was gradually used for more
      complex cases. We excluded 10 hips (10 patients) in which the standardized
      treatment was not achieved and no offset correction or acetabular rim trimming
      was performed. Of the remaining 52 hips (50 patients), 39 hips underwent isolated
      femoral offset correction, four hips isolated acetabular rim trimming, and nine
      hips both procedures. At a mean followup of 7 years (range, 5-11 years), the
      Merle d'Aubigne clinical score was obtained and plain radiographs were examined
      (Tonnis grade, heterotopic ossification, lateral center-edge [LCE] angle,
      acetabular index [AI], extrusion index, alpha angle, and pistol grip deformity).
      Cumulative survivorship was calculated according to Kaplan-Meier using conversion
      to THA, progression of osteoarthritis (one or more Tonnis grades), or poor
      clinical outcome (Merle d'Aubigne score < 15 points) as endpoints. Cox regression
      analysis was used to identify univariate factors associated with revision
      surgery. RESULTS: At last followup we detected a significant but possibly not
      clinically relevant increase in Merle d'Aubigne scores from preoperative levels
      to latest followup (14 +/- 1 versus 16 +/- 2, mean difference 2 points with a 95%
      confidence interval [95% CI] -3 to 7, p < 0.001). Six hips showed progression of
      osteoarthritis. Cumulative survivorship (hips free from conversion to THA,
      progression of osteoarthritis, or poor clinical outcome) of hips treated with hip
      arthroscopy for FAI at a mean followup of 7 years was 81% (95% CI, 68%-95%). Two
      patients (two hips, 4%) underwent THA at 7 and 9 years, respectively. An
      increased preoperative acetabular coverage (LCE angle, AI), increased offset in
      the superior portion of the femoral neck (pistol grip deformity), and a remaining
      pistol grip deformity postoperatively were associated with revision surgery. Any
      treatment of the labrum did not influence the outcome. Factors associated with
      failure could not be identified. CONCLUSIONS: In this series of patients with
      arthroscopic treatment of symptomatic FAI, hip arthroscopy resulted in an intact
      hip without progression of osteoarthritis and with a Merle d'Aubigne score of >=
      15 points in 81% of patients at 7-year followup. Increased acetabular coverage
      and femoral pistol grip deformity were risk factors for revision surgery. LEVEL
      OF EVIDENCE: Level IV, therapeutic study.

PMID- 27718124
TI  - The impact of manual threshold selection in medical additive manufacturing.
AB  - PURPOSE: Medical additive manufacturing requires standard tessellation language
      (STL) models. Such models are commonly derived from computed tomography (CT)
      images using thresholding. Threshold selection can be performed manually or
      automatically. The aim of this study was to assess the impact of manual and
      default threshold selection on the reliability and accuracy of skull STL models
      using different CT technologies. METHOD: One female and one male human cadaver
      head were imaged using multi-detector row CT, dual-energy CT, and two cone-beam
      CT scanners. Four medical engineers manually thresholded the bony structures on
      all CT images. The lowest and highest selected mean threshold values and the
      default threshold value were used to generate skull STL models. Geometric
      variations between all manually thresholded STL models were calculated.
      Furthermore, in order to calculate the accuracy of the manually and default
      thresholded STL models, all STL models were superimposed on an optical scan of
      the dry female and male skulls ("gold standard"). RESULTS: The intra- and inter
      observer variability of the manual threshold selection was good (intra-class
      correlation coefficients >0.9). All engineers selected grey values closer to soft
      tissue to compensate for bone voids. Geometric variations between the manually
      thresholded STL models were 0.13 mm (multi-detector row CT), 0.59 mm (dual-energy
      CT), and 0.55 mm (cone-beam CT). All STL models demonstrated inaccuracies ranging
      from -0.8 to +1.1 mm (multi-detector row CT), -0.7 to +2.0 mm (dual-energy CT),
      and -2.3 to +4.8 mm (cone-beam CT). CONCLUSIONS: This study demonstrates that
      manual threshold selection results in better STL models than default
      thresholding. The use of dual-energy CT and cone-beam CT technology in its
      present form does not deliver reliable or accurate STL models for medical
      additive manufacturing. New approaches are required that are based on pattern
      recognition and machine learning algorithms.

PMID- 27718123
TI  - PPARgamma regulates inflammatory reaction by inhibiting the MAPK/NF-kappaB
      pathway in C2C12 skeletal muscle cells.
AB  - Excessive exercise induces an inflammatory response caused by oxidative stress,
      which delays recovery of damaged muscle fibers. The reduction of inflammatory
      response is important for skeletal muscle homeostasis. Peroxisome proliferator
      activated receptor gamma (PPARgamma) is an anti-inflammatory molecule, but the
      role of PPARgamma in skeletal muscle as anti-inflammatory activity is not clear.
      Thus, this study examined the anti-inflammatory role of PPARgamma against H2O2
      induced oxidative stress in skeletal muscle. Sprague Dawley (SD) rats were
      exercised on a treadmill to induce oxidative stress. In vitro oxidative stress
      was evaluated in differentiated C2C12 cells stimulated using 200 MUM H2O2.
      Inflammation-related molecules were determined by immunohistochemistry and
      Western blot analysis. Expressions of the inflammatory molecules tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), cyclooxygenase-2 (COX
      2), and matrix metalloproteinase-2 (MMP-2) in muscles of the acute exercise group
      were highly increased. PPARgamma was also highly expressed in these muscles.
      These inflammatory molecules were also markedly increased in C2C12 cells with
      H2O2 stimulation. However, PPARgamma overexpression in C2C12 transfected by
      Ad/PPARgamma dramatically reduced the inflammatory molecules. PPARgamma also
      enhanced the anti-oxidants molecules like Cu/Zn-SOD, Mn-SOD, and hemeoxygenase-1
      by reducing the generation of ROS, even in the presence of H2O2. PPARgamma
      displayed dual anti-inflammatory and anti-oxidant roles by inhibiting the mitogen
      activated protein kinase (MAPK) pathway and translocation of nuclear
      transcriptional factor-kappaB (NF-kappaB) from the cytosol to the nucleus. These
      results demonstrate a potential role of PPARgamma in protecting muscle fibers
      against oxidative stress caused by excessive acute exercise due to its anti
      inflammatory and anti-oxidant activity exerted by inhibition of the MAPK/NF
      kappaB pathway.

PMID- 27718125
TI  - Expression and significance of Hippo/YAP signaling in glioma progression.
AB  - Dysregulation of Hippo/YAP signaling leads to aberrant cell growth and neoplasia.
      Although the roles and regulation of Hippo/YAP signaling were extensively studied
      in cancer biology recently, study systematically checking the expression pattern
      of core components of this pathway at the tumor tissue level remains lacking. In
      this study, we thoroughly examined the profile of core components of Hippo/YAP
      signaling in patient specimens both at the mRNA and at protein levels. We found
      that the mRNA level of YAP1/TAZ and their target genes, CRY61, CTGF, and BIRC5,
      was remarkably amplified in glioma tissues. Consistently, the protein level of
      YAP1/TAZ increased and meanwhile those of p-YAP1/p-TAZ and LATS1/2 decreased in
      gliomas. Unexpectedly, both the mRNA and protein levels of MST1/2 increased in
      the glioma tissues, inconsistent with its presumed tumor suppressor identity. In
      addition, over-expression of LATS2 decreased, while over-expression of YPA1
      increased the cell proliferation ability. Furthermore, based on the data from the
      free public database, YAP1/TAZ and BIRC5 were positively associated with the
      prognosis of glioma patients, while LATS1/2 exhibited negative correlation with
      the glioma patient prognosis. Collectively, we deduce that, in glioma tissue
      context, MST1/2 may not be the essential component of the hippo/YAP pathway.
      Moreover, our findings uncover a new evidence supporting that YAP1/TAZ-BIRC5
      might be abnormally activated due to LATS1/2 down-regulation, which in turn
      promote the occurrence and development of gliomas, paving the way to identify the
      potential therapeutic molecular target for gliomas.

PMID- 27718126
TI  - Suppression of CD26 inhibits growth and metastasis of pancreatic cancer.
AB  - CD26/DPPIV is a glycosylated transmembrane type II protein and has a multitude of
      biological functions, while its impact on the malignant phenotypes of cancer
      cells has not been fully understood. This study aimed to investigate the effect
      of CD26 on growth and metastasis of pancreatic cancer cells in vitro and in vivo.
      We found in this study that CD26 expression was higher in cell lines that derived
      from the metastatic sites than those from the primary tumor sites. In specimens
      of pancreatic cancer patients, CD26 expression was higher in cancerous tissues
      than in paired normal tissues. In in vitro experiments, knockdown of CD26
      expression inhibited cell growth, migration, invasion, colony formation, and
      increased cell apoptosis of pancreatic cancer cells. Knockdown of CD26 also
      decreased tumor growth and liver metastasis in vivo by using xenograft animal
      models. Suppression of CD26 could inhibit expression of epithelial-mesenchymal
      transition (EMT) regulatory genes. Our results indicated that CD26 may represent
      a new therapeutic target for pancreatic cancer.

PMID- 27718127
TI  - Rab14 is overexpressed in ovarian cancers and promotes ovarian cancer
      proliferation through Wnt pathway.
AB  - The Rab GTPase family protein Rab14 has been implicated in cancer development.
      However, its clinical significance in ovarian cancers and its biological effects
      have not been examined. The present study aims to examine the clinical
      significance, biological roles, and molecular mechanism of Rab14 in ovarian
      cancer progression. We examined expression pattern of Rab14 in 122 cases of
      ovarian cancer specimens using immunohistochemistry and found Rab14
      overexpression correlated with FIGO stage (p = 0.0041). We depleted Rab14 in
      SKOV3 cells using siRNA and overexpressed Rab14 in SW626 cells. Knockdown of
      Rab14 inhibited cell growth and invasion while its overexpression facilitated
      cell growth and invasion. In addition, Rab14 overexpression increased paclitaxel
      resistance in SW626 cells while its depletion reduced drug resistance. Then, we
      investigated the role of Rab14 in the regulation of WNT/beta-catenin signaling,
      demonstrating Rab14 overexpression regulated GSK3beta phosphorylation and nuclear
      beta-catenin accumulation. Rab14 depletion inhibited while its overexpression
      enhanced TCF transcriptional activity with corresponding change of Wnt target
      genes including MMP7 and c-myc. Wnt inhibitor abolished the effect of Rab14 on
      cell proliferation and Wnt target genes. In conclusion, the present study
      demonstrated that Rab14 promotes aggressiveness of ovarian cancer cell through,
      at least partly, Wnt signaling pathway.

PMID- 27718129
TI  - The readiness of emergency and trauma care in low- and middle-income countries: a
      cross-sectional descriptive study of 42 public hospitals in Albania.
AB  - BACKGROUND: Traumatic injuries have become a substantial but neglected epidemic
      in low- and middle-income countries (LMICs), but emergency rooms (ERs) in these
      countries are often staffed with healthcare providers who have minimal emergency
      training and experience. The aim of this paper was to describe the specialized
      training, available interventions, and the patient management strategies in the
      ERs in Albanian public hospitals. METHODS: A cross-sectional descriptive study of
      42 ERs in the Republic of Albania between September 5, 2014, and December 29,
      2014 was performed. Assessment subcategories included the following: (1)
      specialized training and/or certifications possessed by healthcare providers, (2)
      interventions performed in the ER, and (3) patient management strategies.
      RESULTS: Across the 42 ERs surveyed, less than half (37.1-42.5 %) of physicians
      and one third of nurses (7.1-26.0 %) working in the ERs received specialized
      trauma training. About half (47.9-57.1 %) of the ER physicians and one fifth of
      the nurses (18.3-22.9 %) possessed basic life support certification. This survey
      demonstrated some significant differences in the emergency medical care provided
      between primary, secondary, and tertiary hospitals across Albania (the
      significance level was set at 0.05). Specifically, these differences involved
      spinal immobilization (p = 0.01), FAST scan (p = 0.04), splinting (p = 0.01),
      closed reduction of displaced fractures (p = 0.02), and nurses performing
      cardiopulmonary resuscitation (CPR) (p = 0.01). Between 50.0 and 71.4 % of the
      facilities cited a combined lack of training and supplies as the reason for not
      offering interventions such as rapid sequence induction, needle thoracotomy,
      chest tube insertion, and thrombolysis. Mass casualty triage was utilized among
      39.1 % primary hospitals, 41.7 % of secondary, and 28.6 % of tertiary.
      CONCLUSIONS: The emergency services in Albania are currently staffed with
      inadequately trained personnel, who lack the equipment and protocols to meet the
      needs of the population.

PMID- 27718128
TI  - Diverse roles of miR-335 in development and progression of cancers.
AB  - MicroRNAs (miRNAs), a series of small noncoding RNAs that regulate gene
      expression at the post-transcriptional/translational level, are pivotal in cell
      differentiation, biological development, occurrence, and development of diseases,
      especially in cancers. Early studies have shown that miRNA-335 (miR-335) is
      widely dysregulated in human cancers and play critical roles in tumorigenesis and
      tumor progression. In this review, we aim to summarize the regulation of miR-335
      expression mechanisms in cancers. We focus on the target genes regulated by miR
      335 and its downstream signaling pathways involved in the biological effects of
      tumor growth, invasion, and metastasis both in vitro and in vivo, and analyze the
      relationships between miR-335 expression and the clinical characteristics of
      tumors as well as its effects on prognosis. The collected evidences support the
      potential use of miR-335 in prognosis and diagnosis as well as the therapeutic
      prospects of miR-335 in cancers.

PMID- 27718130
TI  - Tissue reaction of deproteinized bovine bone matrix grafting in ectopic site:
      histological study on sheep.
AB  - The aim of this paper was to evaluate through histological analysis of the tissue
      reaction of deproteinized bovine bone matrix (DBBM) when inserted into the site
      of intramuscular ectopic sheep. In this study, 16 sheep received 3 groups and
      these were divided into 2 experimental times: Group 1-sham group, Group 2
      particulate autogenous bone and Group 3-DBBM granules. All animals underwent
      surgical procedures for insertion of materials in an ectopic site (muscles of the
      lower back and after 3 and 6 months postoperatively, the samples were evaluated
      by histological analysis. The results indicated that the Sham group showed dense
      collagen fibers and thin, characterizing fibrosis at 3 and 6 months. In the
      autograft group there was a significant amount of collagen deposition and
      decreased inflammation at 6 months postoperatively. Group of DBBM, it was noted
      the presence of dense connective tissue and surrounding remaining particles was
      observed the formation of with osteoid characteristic tissue. The DBBM
      demonstrated biocompatibility, osteoconductivity and small osteogenesis capacity
      on ectopic site.

PMID- 27718131
TI  - The false academy: predatory publishing in science and bioethics.
AB  - This paper describes and discusses the phenomenon 'predatory publishing', in
      relation to both academic journals and books, and suggests a list of
      characteristics by which to identify predatory journals. It also raises the
      question whether traditional publishing houses have accompanied rogue publishers
      upon this path. It is noted that bioethics as a discipline does not stand
      unaffected by this trend. Towards the end of the paper it is discussed what can
      and should be done to eliminate or reduce the effects of this development. The
      paper concludes that predatory publishing is a growing phenomenon that has the
      potential to greatly affect both bioethics and science at large. Publishing
      papers and books for profit, without any genuine concern for content, but with
      the pretence of applying authentic academic procedures of critical scrutiny,
      brings about a worrying erosion of trust in scientific publishing.

PMID- 27718133
TI  - Erratum to: 'Influence of Multi-Gene Allele Combinations on Grain Size of Rice
      and Development of a Regression Equation Model to Predict Grain Parameters'.

PMID- 27718132
TI  - The Therapy Attitudes and Process Questionnaire: A Brief Measure of Factors
      Related to Psychotherapy Appointment Attendance.
AB  - BACKGROUND: Patient non-attendance and dropout remains problematic in mental
      health settings. The theory of planned behavior (TPB) has proven useful in
      understanding such challenges in a variety of healthcare settings, but the
      absence of an adequate measure in mental health has hampered research in this
      area. OBJECTIVE: The aim of the current study was to develop and conduct an
      initial psychometric investigation of a brief measure, the Therapy Attitudes and
      Process Questionnaire (TAP), utilizing the TPB to understand factors associated
      with attendance in mental health settings. METHODS: We used a quantitative survey
      based design and administered the TAP to 178 adult participants who were engaged
      in individual or group psychotherapy. A subsample also provided data to assess
      validity and reliability. RESULTS: A four-factor solution was revealed through
      exploratory factor analysis and accounted for approximately 75 % of the variance
      in scores. Factors corresponded to those predicted by the TPB. Analyses supported
      the reliability, validity, and internal consistency of the measure. CONCLUSIONS:
      Results suggest that the TAP may be a useful tool for examining patients'
      attitudes and beliefs about attending psychotherapy appointments. The TAP can be
      used to better understand patients' intentions, attitudes, perceptions of
      behavioral control, and subjective norms relating to psychotherapy attendance.
      This understanding may facilitate improved outcomes for patients and clinicians.

PMID- 27718134
TI  - Postgastrectomy follow-up in the West: evidence base, guidelines, and daily
      practice.
AB  - Follow-up after gastrectomy for gastric cancer has several purposes, including
      management of side effects of surgery, oncological recurrence surveillance,
      psychological support, and data collection for research. How follow-up after
      gastrectomy, and especially recurrence surveillance, is performed differs
      immensely between different Western countries, despite guidelines from Western
      oncological organizations quite unanimously advocating symptom-driven
      surveillance, without scheduled cross-sectional imaging, endoscopies, or analysis
      of tumor markers. Given a complete lack of randomized data, the available body of
      observational data does not support intensive routine surveillance for recurrent
      disease. Moreover, studies of other cancers have shown a negative emotional
      impact of routine surveillance. There is an apparent need for randomized
      controlled trials to address the issue of optimized strategies for
      postgastrectomy recurrence surveillance.

PMID- 27718135
TI  - Mechanisms for the induction of gastric cancer by Helicobacter pylori infection:
      aberrant DNA methylation pathway.
AB  - Multiple pathogenic mechanisms by which Helicobacter pylori infection induces
      gastric cancer have been established in the last two decades. In particular,
      aberrant DNA methylation is induced in multiple driver genes, which inactivates
      them. Methylation profiles in gastric cancer are associated with specific
      subtypes, such as microsatellite instability. Recent comprehensive and integrated
      analyses showed that many cancer-related pathways are more frequently altered by
      aberrant DNA methylation than by mutations. Aberrant DNA methylation can even be
      present in noncancerous gastric mucosae, producing an "epigenetic field for
      cancerization." Mechanistically, H. pylori-induced chronic inflammation, but not
      H. pylori itself, plays a direct role in the induction of aberrant DNA
      methylation. The expression of three inflammation-related genes, Il1b, Nos2, and
      Tnf, is highly associated with the induction of aberrant DNA methylation.
      Importantly, the degree of accumulated aberrant DNA methylation is strongly
      correlated with gastric cancer risk. A recent multicenter prospective cohort
      study demonstrated the utility of epigenetic cancer risk diagnosis for
      metachronous gastric cancer. Suppression of aberrant DNA methylation by a
      demethylating agent was shown to inhibit gastric cancer development in an animal
      model. Induction of aberrant DNA methylation is the major pathway by which H.
      pylori infection induces gastric cancer, and this can be utilized for
      translational opportunities.

PMID- 27718137
TI  - Short-term surgical outcomes from a phase III study of laparoscopy-assisted
      versus open distal gastrectomy with nodal dissection for clinical stage IA/IB
      gastric cancer: Japan Clinical Oncology Group Study JCOG0912.
AB  - BACKGROUNDS: No confirmatory randomized controlled trials (RCTs) have evaluated
      the efficacy of laparoscopy-assisted distal gastrectomy (LADG) compared with open
      distal gastrectomy (ODG). We performed an RCT to confirm that LADG is not
      inferior to ODG in efficacy. METHODS: We conducted a multi-institutional RCT.
      Eligibility criteria included histologically proven gastric adenocarcinoma in the
      middle or lower third of the stomach, clinical stage I tumor. Patients were
      preoperatively randomized to ODG or LADG. This study is now in the follow-up
      stage. The primary endpoint is relapse-free survival (RFS) and the primary
      analysis is planned in 2018. Here, we compared the surgical outcomes of the two
      groups. This trial was registered at the UMIN Clinical Trials Registry as
      UMIN000003319. RESULTS: Between March 2010 and November 2013, 921 patients (LADG
      462, ODG 459) were enrolled from 33 institutions. Operative time was longer in
      LADG than in ODG (median 278 vs. 194 min, p < 0.001), while blood loss was
      smaller (median 38 vs. 115 ml, p < 0.001). There was no difference in the overall
      proportion with in-hospital grade 3-4 surgical complications (3.3 %: LADG, 3.7 %:
      ODG). The proportion of patients with elevated serum AST/ALT was higher in LADG
      than in ODG (16.4 vs. 5.3 %, p < 0.001). There was no operation-related death in
      either arm. CONCLUSIONS: This trial confirmed that LADG was as safe as ODG in
      terms of adverse events and short-term clinical outcomes. LADG may be an
      alternative procedure in clinical IA/IB gastric cancer if the noninferiority of
      LADG in terms of RFS is confirmed.

PMID- 27718136
TI  - Global chemotherapy development for gastric cancer.
AB  - To combat the dismal mortality rates from metastatic gastric adenocarcinoma
      (GAC), new drugs and treatment strategies are needed. Today, metastatic GAC is
      predominantly treated by empiric chemotherapy. Combination of two cytotoxic
      agents has become commonplace in North America, Europe, and Asia. Human epidermal
      growth factor 2 (HER2) overexpression (protein or gene copy numbers) has resulted
      in the addition of trastuzumab in the first-line chemotherapy combination in
      patients whose tumor is HER2 positive. The addition of trastuzumab in this select
      population has provided a modest survival advantage. In this review we trace the
      global development of systemic therapy in patients with metastatic GAC and ponder
      what lies in the future.

PMID- 27718138
TI  - Stress test of a biological early warning system with zebrafish (Danio rerio).
AB  - The aim of this work was to develop a novel methodology to stress test the
      diagnostic capability of a video tracking system with zebrafish (Danio rerio),
      against two pre-established disturbances. Eight different treatments were tested
      varying the presence or absence of a toxicant (NaOCl) and two disturbances: the
      passing of a shadow (mimicking a predator) and entrapment of the fish. The
      concentration tested corresponded to a sublethal (1 % 24 h-LC50) and short term
      exposure (2 h). A total of 56 organisms were tested resulting in 112 diagnoses
      (before and after the contamination). A statistical model of diagnosis was
      developed using Self-organizing Map (SOM) and Correspondence Analysis (CA).
      Sensitivity, specificity, accuracy, false positive and false negative values were
      calculated to evaluate the diagnostic performance. The disturbances did not
      negatively affect the capability of the model. In the presence of at least one of
      these variables, the diagnostic performance was similar or even superior to the
      baseline results without disturbances. Furthermore, the system produced a large
      number of correct diagnoses, at an ecologically relevant concentration of
      exposure, in a non-invasive way.

PMID- 27718139
TI  - Feasibility and diagnostic performance of fractional flow reserve measurement
      derived from coronary computed tomography angiography in real clinical practice.
AB  - Non-invasive fractional flow reserve measured by coronary computed tomography
      angiography (FFRCT) has demonstrated a high diagnostic accuracy for detecting
      coronary artery disease (CAD) in selected patients in prior clinical trials.
      However, feasibility of FFRCT in unselected population have not been fully
      evaluated. Among 60 consecutive patients who had suspected significant CAD by
      coronary computed tomography angiography (CCTA) and were planned to undergo
      invasive coronary angiography, 48 patients were enrolled in this study comparing
      FFRCT with invasive fractional flow reserve (FFR) without any exclusion criteria
      for the quality of CCTA image. FFRCT was measured in a blinded fashion by an
      independent core laboratory. FFRCT value was evaluable in 43 out of 48 (89.6 %)
      patients with high prevalence of severe calcification in CCTA images [calcium
      score (CS) >400: 40 %, and CS > 1000: 19 %). Per-vessel FFRCT value showed good
      correlation with invasive FFR value (Spearman's rank correlation = 0.69, P <
      0.001). The area under the receiver operator characteristics curve (AUC) of FFRCT
      was 0.87. Per-vessel accuracy, sensitivity, specificity, positive predictive
      value, and negative predictive value were 68.6, 92.9, 52.4, 56.5, and 91.7 %,
      respectively. Even in eight patients (13 vessels) with extremely severely
      calcified lesions (CS > 1000), per-vessel FFRCT value showed a diagnostic
      performance similar to that in patients with CS <= 1000 (Spearman's rank
      correlation = 0.81, P < 0.001). FFRCT could be measured in the majority of
      consecutive patients who had suspected significant CAD by CCTA in real clinical
      practice and demonstrated good diagnostic performance for detecting
      hemodynamically significant CAD even in patients with extremely severe calcified
      vessels.

PMID- 27718140
TI  - Prediction of clinical outcome by myocardial CT perfusion in patients with low
      risk unstable angina pectoris.
AB  - The prognostic implications of myocardial computed tomography perfusion (CTP)
      analyses are unknown. In this sub-study to the CATCH-trial we evaluate the
      ability of adenosine stress CTP findings to predict mid-term major adverse
      cardiac events (MACE). In 240 patients with acute-onset chest pain, yet normal
      electrocardiograms and troponins, a clinically blinded adenosine stress CTP scan
      was performed in addition to conventional diagnostic evaluation. A reversible
      perfusion defect (PD) was found in 38 patients (16 %) and during a median follow
      up of 19 months (range 12-22 months) 25 patients (10 %) suffered a MACE (cardiac
      death, non-fatal myocardial infarction and revascularizations). Accuracy for the
      prediction of MACE expressed as the area under curve (AUC) on receiver-operating
      characteristic curves was 0.88 (0.83-0.92) for visual assessment of a PD and 0.80
      (0.73-0.85) for stress TPR (transmural perfusion ratio). After adjustment for the
      pretest probability of obstructive coronary artery disease, both detection of a
      PD and stress TPR were significantly associated with MACE with an adjusted hazard
      ratio of 39 (95 % confidence interval 11-134), p < 0.0001, for visual
      interpretation and 0.99 (0.98-0.99) for stress TPR, p < 0.0001. Patients with a
      PD volume covering >10 % of the LV myocardium had a worse prognosis compared to
      patients with a PD covering <10 % of the LV myocardium, p = 0.0002. The optimal
      cut-off value of the myocardial PD extent to predict MACE was 5.3 % of the left
      ventricle [sensitivity 84 % (64-96), specificity 95 % (91-97)]. Myocardial CT
      perfusion parameters predict mid-term clinical outcome in patients with recent
      acute-onset chest pain.

PMID- 27718141
TI  - Promoting interdomain analogical transfer: When creating a problem helps to solve
      a problem.
AB  - Research on analogical thinking has devised several ways of promoting an abstract
      encoding of base analogs, thus rendering them more retrievable during later
      encounters with similar situations lacking surface similarities. Recent studies
      have begun to explore ways of facilitating transfer at retrieval time, which
      could facilitate the retrieval of distant analogs learned within contexts that
      were not specially directed to emphasize their abstract structure. Such studies
      demonstrate that comparing a target problem to an analogous problem helps
      students retrieve base analogs that lack surface similarities. To devise more
      portable ways of enhancing analogical transfer, Experiment 1 replicated Kurtz and
      Loewenstein's (Memory & Cognition, 35, 334-341, 2007) target-comparison procedure
      with an additional condition in which participants compared the target to a
      nonanalogous problem before attempting to reach its solution. Although comparing
      two analogous targets outperformed the standard transfer condition in promoting
      analogical transfer, comparing nonanalogous problems did not yield a transfer
      advantage. Based on prior studies that showed that the activity of creating
      analogous problems during their initial encoding elicits a more abstract
      representation of base analogs, in Experiment 2 we assessed whether constructing
      a second analogous target problem at retrieval time helps participants retrieve
      superficially dissimilar base analogs. As predicted, target invention increased
      the retrieval of distant sources. In both experiments we found an association
      between the quality of the generated schemas and the probability of retrieving a
      distant base analog from memory.

PMID- 27718142
TI  - The effect of anomalous utterances on language production.
AB  - Speakers sometimes encounter utterances that have anomalous linguistic features.
      Are such features registered during comprehension and transferred to speakers'
      production systems? In two experiments, we explored these questions. In a
      syntactic-priming paradigm, speakers heard prime sentences with novel or
      intransitive verbs as part of prepositional-dative or double-object structures
      (e.g., The chef munded the cup to the burglar or The doctor existed the pirate
      the balloon). Speakers then described target pictures eliciting the same
      structures, using the same or different novel or intransitive verbs. Speakers
      overall described targets with the same structures as the primes (abstract
      syntactic priming), but more so when the primes and targets had the same novel or
      intransitive verbs (a lexical boost), an effect that was only observed when the
      novel words served as the verbs in both the prime and target sentences. Such a
      lexical boost could only manifest if speakers formed associations between the
      verbs and structures in the primes during comprehension, and if these
      associations were then transferred to their production systems. We thus showed
      that anomalous utterance features are not ignored but persist (at least) in
      speakers' immediately subsequent production.

PMID- 27718143
TI  - Concentration of Donepezil in the Cerebrospinal Fluid of AD Patients: Evaluation
      of Dosage Sufficiency in Standard Treatment Strategy.
AB  - Although some studies have described the pharmacokinetics and pharmacodynamics of
      donepezil in the peripheral compartment, studies focused on drug transport across
      the blood-brain barrier are still very rare. To our knowledge, the fluctuation in
      the cerebrospinal fluid concentration of donepezil after administration of the
      drug has not been described in the literature so far. We recruited 16 patients
      regularly taking a standard therapeutic dose of donepezil (10 mg per day). All
      patients (Caucasian race) were treated for at least three months with a stable
      dose of 10 mg per day prior to sample collection. Patients were divided into two
      groups depending on the time of plasma and cerebrospinal fluid sampling: 12 h (n
      = 9; 4 M/5F aged 78.68 +/- 7.35 years) and 24 h (n = 7; 3 M/4F aged 77.14 +/-
      5.87 years) after donepezil administration. The cerebrospinal fluid sample was
      collected by standard lumbar puncture technique using a single-use traumatic
      needle. The samples were analysed on an Agilent 1260 Series liquid chromatograph
      comprising a degasser, a quaternary pump, a light-tight autosampler unit set, a
      thermostated column compartment, and a UV/VIS detector. Agilent ChemStation
      software, the statistical software Prism4, version 5.0 (GraphPad Software, USA),
      and IBM(r) SPSS(r) Statistics were used for the analysis of the results. The
      difference in plasma concentration of donepezil after 12 h (mean +/- SEM; 39.99
      +/- 5.90 ng/ml) and after 24 h (29.38 +/- 1.71 ng/ml) was nonsignificant. In
      contrast, the donepezil concentration in the cerebrospinal fluid was
      significantly higher in the 24-h interval (7.54 +/- 0.55 ng/ml) compared with the
      12-h interval (5.19 +/- 0.83 ng/ml, which is ~70 % based on mean cerebrospinal
      fluid values). Based on these data, it is plausible to predict that donepezil
      might produce a stronger AChE inhibition in the brain at 24 h compared with 12 h
      following the administration. This information may help physicians individually
      adjust the time of drug administration in the patients according to time course
      of the disease symptoms.

PMID- 27718144
TI  - Cardiomyopathy as presenting sign of glycogenin-1 deficiency-report of three
      cases and review of the literature.
AB  - We describe a new type of cardiomyopathy caused by a mutation in the glycogenin-1
      gene (GYG1). Three unrelated male patients aged 34 to 52 years with
      cardiomyopathy and abnormal glycogen storage on endomyocardial biopsy were
      homozygous for the missense mutation p.Asp102His in GYG1. The mutated glycogenin
      1 protein was expressed in cardiac tissue but had lost its ability to
      autoglucosylate as demonstrated by an in vitro assay and western blot analysis.
      It was therefore unable to form the primer for normal glycogen synthesis. Two of
      the patients showed similar patterns of heart dilatation, reduced ejection
      fraction and extensive late gadolinium enhancement on cardiac magnetic resonance
      imaging. These two patients were severely affected, necessitating cardiac
      transplantation. The cardiomyocyte storage material was characterized by large
      inclusions of periodic acid and Schiff positive material that was partly
      resistant to alpha-amylase treatment consistent with polyglucosan. The storage
      material had, unlike normal glycogen, a partly fibrillar structure by electron
      microscopy. None of the patients showed signs or symptoms of muscle weakness but
      a skeletal muscle biopsy in one case revealed muscle fibres with abnormal
      glycogen storage. Glycogenin-1 deficiency is known as a rare cause of skeletal
      muscle glycogen storage disease, usually without cardiomyopathy. We demonstrate
      that it may also be the cause of severe cardiomyopathy and cardiac failure
      without skeletal muscle weakness. GYG1 should be included in cardiomyopathy gene
      panels.

PMID- 27718146
TI  - Microbial interactions with chromium: basic biological processes and applications
      in environmental biotechnology.
AB  - Chromium (Cr) is a highly toxic metal for microorganisms as well as plants and
      animal cells. Due to its widespread industrial use, Cr has become a serious
      pollutant in diverse environmental settings. The hexavalent form of the metal,
      Cr(VI), is considered a more toxic species than the relatively innocuous and less
      mobile Cr(III) form. The study of the interactions between microorganisms and Cr
      has been helpful to unravel the mechanisms allowing organisms to survive in the
      presence of high concentrations of Cr(VI) and to detoxify and remove the
      oxyanion. Various mechanisms of interactions with Cr have been identified in
      diverse species of bacteria and fungi, including biosorption, bioaccumulation,
      reduction of Cr(VI) to Cr(III), and chromate efflux. Some of these systems have
      been proposed as potential biotechnological tools for the bioremediation of Cr
      pollution using bioreactors or by in situ treatments. In this review, the
      interactions of microorganisms with Cr are summarised, emphasising the importance
      of new research avenues using advanced methodologies, including proteomic,
      transcriptomic, and metabolomic analyses, as well as the use of techniques based
      on X-ray absorption spectroscopy and electron paramagnetic resonance
      spectroscopy.

PMID- 27718147
TI  - A morel improved growth and suppressed Fusarium infection in sweet corn.
AB  - A post-fire morel collected from Populus simonii stands in Mt. Qingling was
      identified as Morchella crassipes Mes-20 by using nuclear ribosomal DNA internal
      transcribed spacer phylogeny. It was inoculated into sweet corn to observe
      colonized roots in purified culture and in greenhouse experiments. The elongation
      and maturation zones of sweet corn were remarkably colonized at the cortex
      intercellular and intracellular cells, vessel cells, and around the Casparian
      strip, forming ectendomycorrhiza-like structures. Colonization was also observed
      in the zone of cell division proximal to the root cap. Greenhouse assays with
      sweet corn showed that this morel stimulated the development of the root system
      and significantly increased the dry root biomass. M. crassipes also significantly
      reduced the incidence of Fusarium verticillioides in the kernels of mature ears
      when inoculated into young ears before Fusarium inoculation and prevented
      Fusarium infection in corn ears compared with that of the control in the
      greenhouse. When grown under axenic conditions, M. crassipes produced the
      phytohormones abscisic acid, indole-3-acetic acid, and salicylic acid. The
      benefits to plants elicited by M. crassipes may result from these phytohormones
      which may improve the drought resistance, biomass growth and resistance to
      Fusarium.

PMID- 27718148
TI  - Modern morphological engineering techniques for improving productivity of
      filamentous fungi in submerged cultures.
AB  - Morphological engineering techniques have recently gained popularity as they are
      used for increasing the productivity of a variety of metabolites and enzymes in
      fungi growing in submerged cultures. Their action is mainly associated with the
      changes they evoke in fungal morphology. Traditional morphological engineering
      approaches include manipulation of spore concentration, pH-shifting and
      mechanical stress exerted by stirring and aeration. As the traditional methods
      proved to be insufficient, modern techniques such as changes of medium osmolality
      or addition of mineral microparticles to the media (microparticle-enhanced
      cultivation, MPEC) were proposed. Despite the fact that this area of knowledge is
      still being developed, there are a fair amount of scientific articles concerning
      the cultivations of filamentous fungi with the use of these techniques. It was
      described that in Ascomycetes fungi both MPEC or change of osmolality
      successfully led to the change of mycelial morphology, which appeared to be
      favorable for increased productivity of secondary metabolites and enzymes. There
      are also limited but very promising reports involving the successful application
      of MPEC with Basidiomycetes species. Despite the fact that the mineral
      microparticles behave differently for various microorganisms, being strain and
      particle specific, the low cost of its application is a great benefit. This paper
      reviews the application of the modern morphology engineering techniques. The
      authors critically assess the advantages, shortcomings, and future prospects of
      their application in the cultivation of fungi.

PMID- 27718145
TI  - Newborn screening for mucopolysaccharidoses: a pilot study of measurement of
      glycosaminoglycans by tandem mass spectrometry.
AB  - BACKGROUND: Mucopolysaccharidoses (MPS) are a group of inborn errors of
      metabolism that are progressive and usually result in irreversible skeletal,
      visceral, and/or brain damage, highlighting a need for early diagnosis. METHODS:
      This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS
      from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5).
      Disaccharides were produced from polymer GAGs by digestion with chondroitinase B,
      heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS)
      and mono- and di-sulfated KS were measured by liquid chromatography tandem mass
      spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine
      cutoffs to distinguish patients from controls. Cutoffs were defined as median +
      7* MAD from general newborns. RESULTS: The cutoffs were as follows: HS-0S > 90
      ng/mL; HS-NS > 23 ng/mL, DS > 88 ng/mL; mono-sulfated KS > 445 ng/mL; di-sulfated
      KS > 89 ng/mL and ratio di-KS in total KS > 32 %. All MPS I and II samples were
      above the cutoffs for HS-0S, HS-NS, and DS, and all MPS III samples were above
      cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was
      0.03 % based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9 %
      based upon a combination of HS-0S and HS-NS. CONCLUSIONS: Combination of levels
      of two or more different GAGs improves separation of MPS patients from unaffected
      controls, indicating that GAG measurements are potentially valuable biomarkers
      for newborn screening for MPS.

PMID- 27718149
TI  - The Topology Prediction of Membrane Proteins: A Web-Based Tutorial.
AB  - There is a great need for development of educational materials on the transfer of
      current bioinformatics knowledge to undergraduate students in bioscience
      departments. In this study, it is aimed to prepare an example in silico
      laboratory tutorial on the topology prediction of membrane proteins by
      bioinformatics tools. This laboratory tutorial is prepared for biochemistry
      lessons at bioscience departments (biology, chemistry, biochemistry, molecular
      biology and genetics, and faculty of medicine). The tutorial is intended for
      students who have not taken a bioinformatics course yet or already have taken a
      course as an introduction to bioinformatics. The tutorial is based on step-by
      step explanations with illustrations. It can be applied under supervision of an
      instructor in the lessons, or it can be used as a self-study guide by students.
      In the tutorial, membrane-spanning regions and alpha-helices of membrane proteins
      were predicted by internet-based bioinformatics tools. According to the results
      achieved from internet-based bioinformatics tools, the algorithms and parameters
      used were effective on the accuracy of prediction. The importance of this
      laboratory tutorial lies on the facts that it provides an introduction to the
      bioinformatics and that it also demonstrates an in silico laboratory application
      to the students at natural sciences. The presented example education material is
      applicable easily at all departments that have internet connection. This study
      presents an alternative education material to the students in biochemistry
      laboratories in addition to classical laboratory experiments.

PMID- 27718150
TI  - Randomized clinical trial to comparing efficacy of daily, weekly and monthly
      administration of vitamin D3.
AB  - The comparative efficacy and safety profiles of selected daily 1000 IU, weekly
      7000 IU and monthly 30,000 IU vitamin D 3-not previously investigated-will be
      evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and
      safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose
      (group B), or monthly 30,000 IU dose (group C) of vitamin D3. The present study
      is a controlled, randomized, open-label, multicenter clinical trial, 3  months in
      duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml),
      were included according to the inclusion and exclusion criteria. Dose-responses
      for increases in serum vitamin 25OHD were statistically equivalent for each of
      the three groups: A, B and C. Outcomes were 13.0 +/- 1.5; 12.6 +/- 1.1 and 12.9
      +/- 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly,
      respectively. The treatment of subjects with selected doses restored 25OHD values
      to levels above 20 ng/ml in all groups. Treatment with distinct administration
      frequency of vitamin D3 did not exhibit any differences in safety parameters. The
      daily, weekly and monthly administrations of daily equivalent of 1000 IU of
      vitamin D3 provide equal efficacy and safety profiles.

PMID- 27718151
TI  - Surgical Outcomes for the Ruptured Hepatocellular Carcinoma: Multicenter Analysis
      with a Case-Controlled Study.
AB  - BACKGROUND: While spontaneously ruptured hepatocellular carcinoma (HCC) has a
      poor prognosis, the true impact of a rupture on survival after hepatic resection
      is unclear. METHODS: Fifty-eight patients with ruptured HCC and 1922 with non
      ruptured HCC underwent hepatic resection between 2000 and 2013. To correct the
      difference in the clinicopathological factors between the two groups, propensity
      score matching (PSM) was used at a 1:1 ratio, resulting in a comparison of 42
      patients/group. We investigated outcomes in all patients with ruptured HCC and
      compared outcomes between the two matched groups. RESULTS: Of the 58 patients
      with ruptured HCC, 7 patients (13 %) died postoperatively. Overall survival (OS)
      rate at 5 years after hepatic resection was 37 %. Emergency hepatic resection was
      an independent risk factor for in-hospital death and Child-Pugh class B for
      unfavorable OS in multivariate analysis. Clinicopathological variables were well
      balanced between the two groups after PSM. No significant differences were noted
      in incidence of in-hospital death (ruptured HCC 12 % vs non-ruptured HCC 2 %, p =
      0.202) or OS rate (5/10-year; 42 %/38 % vs 67 %/30 %, p = 0.115). CONCLUSION:
      Emergency hepatic resection should be avoided for ruptured HCC in Child-Pugh
      class B patients. Rupture itself was not a risk for unfavorable surgical
      outcomes.

PMID- 27718153
TI  - Effect of adaptive replanning in patients with locally advanced nasopharyngeal
      carcinoma treated by intensity-modulated radiotherapy: a propensity score matched
      analysis.
AB  - PURPOSE: Limited data have been published regarding the effect of adaptive
      radiotherapy (ART) on clinical outcome in patients with nasopharyngeal carcinoma
      (NPC). We compared the long-term outcomes in patients with locally advanced NPC
      treated by adaptive intensity-modulated radiotherapy (IMRT) replanning versus
      IMRT. METHODS: 200 NPC patients with stage T3/T4 were included between October
      2004 and November 2010. Patients in both treatment groups were matched using
      propensity score matching method at the ratio of 1:1. Clinical outcomes were
      analyzed with Kaplan-Meier method, log-rank test and Cox regression. RESULTS:
      After matching, 132 patients (66 patients in each group) were included for
      analysis. The median follow-up for the IMRT replanning group was 70 months, while
      the IMRT group was 69 months. The 5-year local-regional recurrence-free survival
      (LRFS) rate was higher in IMRT replanning group (96.7 vs. 88.1 %, P = 0.022). No
      significant differences in distant metastasis-free survival (DMFS), progression
      free survival (PFS) and overall survival (OS) were observed between the two
      groups. 21.2 % patients in IMRT replanning group and 28.8 % patients in IMRT
      group had distant metastasis. In multivariable analysis, IMRT replanning was
      identified as an independent prognostic factor for LRFS (hazard ratio 0.229; 95 %
      CI 0.062-0.854; P = 0.028), but not for DMFS, PFS and OS. CONCLUSIONS: IMRT
      replanning provides an improved LRFS for stage T3/T4 NPC patients compared with
      IMRT. Distant metastasis remains the main pattern of treatment failure. No
      significant advantage was observed in DMFS, PFS and OS when adaptive replanning
      was used.

PMID- 27718152
TI  - Differential BMI1, TWIST1, SNAI2 mRNA expression pattern correlation with
      malignancy type in a spectrum of common cutaneous malignancies: basal cell
      carcinoma, squamous cell carcinoma, and melanoma.
AB  - PURPOSE: Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC)
      can be used as a unique model to identify molecular mechanisms to distinguish
      rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma)
      cancer. It is known that epithelial-mesenchymal transition and stemness
      transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in
      metastasis and their dysregulation has been demonstrated in metastatic cancers.
      We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma)
      would be a unique cancer model system to elucidate steps toward cancer invasion
      and metastasis. METHODS: We evaluated the mRNA expression level of BMI1, TWIST1,
      and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along
      with normal tissue samples. RESULTS: We demonstrate downregulation of BMI1 mRNA
      expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001),
      and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is
      seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA
      expression is represented in melanoma samples compared with controls (p = 0.022)
      and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients
      with positive history of cancers. Extremely low mRNA expression of BMI1 is
      detected in patients with positive history of cancers other than skin cancer.
      CONCLUSIONS: These findings provide support for the hypothesis that the spectrum
      of cutaneous cancers could be better understood as a series of gene dosage
      dependent entities with distinct molecular events. Oncogene-induced senescence,
      mechanism of which is still unclear, could be one explanation for these results.

PMID- 27718154
TI  - Prognostic significance of immune cells in the tumor microenvironment and
      peripheral blood of gallbladder carcinoma patients.
AB  - BACKGROUND: The role of the interaction between tumor cells and inflammatory
      cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both
      the tumor immune microenvironment and the host peripheral blood circulatory
      system. In the current study, we examined the prognostic value of inflammatory
      cells in the tumor microenvironment and peripheral blood in patients with GBC.
      METHODS: 98 patients with GBC were recruited in this retrospective study. Using
      immunohistochemistry, we examined tumor-infiltrating CD3+ generic T-cells, CD8+
      cytotoxic T-cells, CD45RO+ memory T-cells, and CD15+ neutrophils. Peripheral
      venous blood samples were also collected, and absolute neutrophil count (ANC),
      absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) were
      measured. The relationships between these variables and patient outcome were
      evaluated. RESULTS: Survival analysis revealed that the density of CD3+ cell
      infiltrates in the tumor microenvironment was positively correlated with overall
      survival (OS) and the density of CD15+ cell infiltrates was negatively correlated
      with the OS. The combined analysis showed that a high density of CD3+ cell
      infiltrates combined with a low density of CD15+ cell infiltrates was an
      independent prognostic factor for GBC. In peripheral blood, survival analysis
      suggested that ANC and NLR were negatively correlated, while ALC was positively
      correlated with OS. Multivariate survival analysis showed that NLR was an
      independent prognostic factor for gallbladder cancer prognosis. CONCLUSIONS: The
      results indicate that the combination of high density of CD3+ cell infiltrates
      combined with a low density of CD15+ cell infiltrates in tumor samples and
      pretreatment peripheral blood NLR were independent prognostic factors in patients
      with GBC.

PMID- 27718155
TI  - Effectiveness and safety of aflibercept for metastatic colorectal cancer:
      retrospective review within an early access program in Spain.
AB  - PURPOSE: In the VELOUR study, aflibercept + FOLFIRI regimen resulted in improved
      survival in metastatic colorectal cancer (mCRC) patients who progressed after
      oxaliplatin. The use of aflibercept outside the clinical trial framework needs to
      be further assessed in terms of effectiveness and tolerability. METHODS: Early
      access to aflibercept through a named patient programme (NPP) was provided to
      mCRC patients receiving FOLFIRI as second-line treatment in Spain. The
      effectiveness of aflibercept was assessed as progression-free survival (PFS)
      achieved within the NPP population. Post hoc analyses on PFS were done according
      to certain baseline characteristics (K-RAS mutation, prior targeted therapy) or
      prognostic factors. RESULTS: Registries from 71 mCRC patients included in the NPP
      were reviewed retrospectively. The median age for the NPP population was 64 years
      (19.7 % aged >=70 years) and 63.4 % patients had >=2 metastases. A median PFS of
      5.3 months (95 % CI, 3.6-8.5 months) was achieved, which did not depend on K-RAS
      mutation status or prior targeted therapy received. The risk of progression or
      death increased in patients with a poor prognosis as per the GERCOR score
      (performance status [PS] 1-2 and increased baseline lactate dehydrogenase [LDH]
      level) compared with patients with a good prognosis (PS 0 and normal LDH level)
      (median PFS: 2.6 vs. 8.3 months, respectively; p = 0.0124). Aflibercept was well
      tolerated, with a manageable toxicity profile. CONCLUSIONS: Bearing in mind the
      differences in sample size, the PFS achieved with the aflibercept + FOLFIRI
      regimen in the real-life practice setting is comparable to that observed in the
      clinical trial setting.

PMID- 27718156
TI  - Patient-derived xenografts for childhood solid tumors: a valuable tool to test
      new drugs and personalize treatments.
AB  - The use of preclinical models is essential in translational cancer research and
      especially important in pediatric cancer given the low incidence of each
      particular type of cancer. Cell line cultures have led to significant advances in
      cancer biology. However, cell lines have adapted to growth in artificial culture
      conditions, thereby undergoing genetic and phenotypic changes which may hinder
      the translational application. Tumor grafts developed in mice from patient tumor
      tissues, generally known as patient-derived xenografts (PDXs), are interesting
      alternative approaches to reproducing the biology of the original tumor. This
      review is focused on highlighting the interest of PDX models in pediatric cancer
      research and supporting strategies of personalized medicine. This review
      provides: (1) a description of the background of PDX in cancer, (2) the
      particular case of PDX in pediatric cancer, (3) how PDX can improve personalized
      medicine strategies, (4) new methods to increase engraftment, and, finally, (5)
      concluding remarks.

PMID- 27718157
TI  - New clinical trials regulation in Spain: analysis of royal decree 1090/2015.
AB  - The coming into force of Directive 2001/20/EC represented a step forward in
      harmonising clinical trial regulation in European countries, guaranteeing a
      uniform protection of subjects participating in clinical research across Europe.
      However, it led to a disproportionate increase in the bureaucratization, and
      thus, it became evident that procedures needed to be simplified without detriment
      to patient's safety. Thus, Regulation 536/2014, that repealed Directive
      2001/20/EC, with the aim of decreasing the growing bureaucratization and
      stimulating clinical research in Europe, established simplified procedures, such
      as regulating a common procedure for authorising trials in Europe, the
      institution of strict assessment timelines, or the definition of new concepts,
      such as "low-intervention clinical trial". The legal form of a Regulation allowed
      the norm to be directly applied to Member States without the need for
      transposition. By means of the new Royal Decree, the national legislation is
      adapted to make the application of the regulation feasible and it allows the
      development of the aspects that the Regulation leaves to national legislation.
      Both documents seek to stimulate clinical research with medicinal products to
      foster knowledge, facilitate transparency, and reinforce subjects' safety. This
      will surely be the case, but with this revision, we will look at the novelties
      and key aspects that are most relevant to investigators and we will analyse the
      consequences for all parties involved in clinical research.

PMID- 27718158
TI  - Perceptions of Oncologists, Healthcare Policy Makers, Patients and the General
      Population on the Value of Pharmaceutical Treatments in Oncology.
AB  - INTRODUCTION: The purpose of this study was to explore the main factors
      explaining the relative weight of the different attributes that determine the
      value of oncologic treatments from the different perspectives of healthcare
      policy makers (HCPM), oncologists, patients and the general population in Spain.
      METHODS: Structured interviews were conducted to assess: (1) the importance of
      the attributes on treatment choice when comparing a new cancer drug with a
      standard cancer treatment; (2) the importance of survival, quality of life (QoL),
      costs and innovation in cancer; and (3) the most worrying side effects related to
      cancer drugs. RESULTS: A total of 188 individuals participated in the study. For
      all participants, when choosing treatments, the best rated characteristics were
      greater efficacy, greater safety, treatment adaptation to patients' individual
      requirements and the rapid reincorporation of patients to their daily activities.
      There were important differences among participants in their opinion about
      survival, QoL and cost. In general, oncologists, patients, and the general
      population gave greater value to gains in QoL than healthcare policy makers.
      Compared to other participants healthcare policy makers gave greater importance
      to the economic impact related to oncology treatments. CONCLUSIONS: Gains in QoL,
      survival, safety, cost and innovation are perceived differently by different
      groups of stakeholders. It is recommended to consider the perspective of
      different stakeholders in the assessment of a new cancer drugs to obtain more
      informed decisions when deciding on the most appropriate treatment to use.
      FUNDING: Eli Lilly & Co, Madrid (Spain).

PMID- 27718159
TI  - Reward-Induced Eating: Therapeutic Approaches to Addressing Food Cravings.
AB  - The homeostatic controls over eating are inextricably linked to the reward
      aspects of eating. The result is an integrated response that coordinates the
      internal milieu with the prevailing environment. Thus, appetite, which reflects a
      complex interaction among the external environment, behavioral profile, and
      subjective states as well as the storage and metabolism of energy, has an
      important role in the regulation of energy balance. In the prevailing food
      environment which offers an abundance of food choices it is likely that the
      motivation to consume from a wide range of delectable foods plays a greater role
      in contributing to overeating than in the past when the motivation to eat was
      largely governed by metabolic need. The response to food-related cues can promote
      strong desires to eat known as cravings by activating the mesocorticolimbic
      dopamine neurocircuitry. Cravings are associated with subsequent eating and
      weight-related outcomes. Being able to control food cravings is a determinant of
      success at adhering to an energy-restricted diet regimen. Increased understanding
      of the neurocircuitry of appetite regulation, especially reward-related eating
      behavior, has provided potential targets for therapeutic anti-obesity agents
      specifically directed at reward mechanisms. The naltrexone-bupropion combination
      and lorcaserin, which are both approved by the US Food and Drug Administration
      (FDA) for long-term weight management, have shown promise in addressing craving
      related eating behavior. Phentermine and liraglutide are approved as
      monotherapies for weight management. Preliminary research suggests that
      liraglutide, as well as phentermine alone or in combination with lorcaserin, may
      be effective in targeting food cravings. Food components such as thylakoid
      membranes have also been shown to influence food cravings. This review explores
      the concepts related to appetite and reward-induced eating behavior, as well as
      the pharmacological options and food-derived components that may be used to
      address food cravings.

PMID- 27718161
TI  - HIV Immune Recovery Inflammatory Syndrome and Central Nervous System
      Paracoccidioidomycosis.
AB  - The immune reconstitution inflammatory syndrome (IRIS) is a deregulated
      inflammatory response to invading microorganisms. It is manifested when there is
      an abrupt change in host immunity from an anti-inflammatory and immunosuppressive
      state to a pro-inflammatory state as a result of rapid depletion or removal of
      factors that promote immune suppression or inhibition of inflammation. The aim of
      this paper is to discuss and re-interpret the possibility of association of
      paracoccidioidomycosis (PCM) with IRIS in the central nervous system (CNS) in a
      case from Brazil published by Silva-Vergara ML. et al. (Mycopathologia 177:137
      141, 6). An AIDS patient who was not receiving medical care developed pulmonary
      PCM successfully treated with itraconazole. The patient developed central nervous
      system PCM (NPCM) after starting the ARV therapy with recovery of immunity and
      control of HIV viral load, although it was not interpreted as IRIS by the
      authors, it fulfills the criteria for CNS IRIS. This could be the first case of
      NPCM associated with IRIS described. Although not frequent, IRIS must be
      considered in PCM patients and HIV, from endemic areas or patients that traveled
      to endemic areas, receiving ARV treatment and with worsening symptoms.

PMID- 27718160
TI  - Reappraisal of Conventional Diagnosis for Dermatophytes.
AB  - Dermatophytoses include a wide variety of diseases involving glabrous skin, nails
      and hair. These superficial infections are a common cause of consultation in
      dermatology. In many cases, their diagnosis is not clinically obvious, and
      mycological analysis therefore is required. Direct microscopic examination of the
      samples using clearing agents provides a quick response to the clinician and is
      usually combined with cultures on specific media, which must be used to overcome
      the growth of contaminating moulds that may hamper the recovery of dermatophytes.
      Accurate identification of the causative agent (i.e. at the species level),
      currently based on morphological criteria, is necessary not only to initiate an
      appropriate treatment but also for setting prophylactic measures. However,
      conventional methods often lack sensitivity and species identification may
      require up to 4 weeks if subcultures are needed. Histological analysis, which is
      considered the "gold standard" for the diagnosis of onychomycoses, is seldom
      performed, and as direct examination, it does not allow precise identification of
      the pathogen. Nevertheless, a particular attention to the quality of clinical
      specimens is warranted. Moreover, the sensitivity of direct examination may be
      greatly enhanced by the use of fluorochromes such as calcofluor white. Likewise,
      sensitivity of the cultures could be enhanced by the use of culture media
      containing antifungal deactivators. With the generalization of molecular
      identification by gene sequencing or MALDI-TOF mass spectrometry, the
      contribution of historical biochemical or physiological tests to species
      identification of atypical isolates is now limited. Nevertheless, despite the
      recent availability of several PCR-based kits and an extensive literature on
      molecular methods allowing the detection of fungal DNA or both detection and
      direct identification of the main dermatophyte species, the biological diagnosis
      of dermatophytosis in 2016 still relies on both direct examination and cultures
      of appropriate clinical specimens.

PMID- 27718162
TI  - Impact of the Use of Regional Poison Control Centers in an Urban EMS Dispatch
      System.
AB  - BACKGROUND: The public commonly calls 911 for unintentional ingestions, rather
      than calling the local poison center. By utilizing a series of scripted
      questions, 911 dispatchers in Los Angeles determine if an ingestion meets "omega
      1" classification. Under such circumstances, the regional poison center is
      contacted prior to dispatch of paramedics. If the poison center advises that the
      patient can remain at home, EMS is not dispatched and the patient is followed at
      home by the poison center. The primary objective is to determine the number of
      averted transports through involvement of a poison center. A secondary objective
      is to determine the potential costs and charges saved with the use of such a
      strategy. METHODS: A retrospective review of all overdose calls with an "omega-1"
      classification to a single EMS system between 1/2008-6/2012. Each call
      culminating in an EMS dispatch was subsequently reviewed by two additional
      reviewers. The cost savings was determined by utilizing data from the Medical
      Expenditure Panel Survey (MEPS) from 2000 to 2010. Monetary values were adjusted
      to 2012 dollars. RESULTS: Three hundred eighteen cases received "omega-1"
      dispatch classification. EMS was dispatched 19 times (5.98 %), and 11 patients
      (3.46 %) were ultimately transported. The most common reasons for transport were
      ambiguity over the ingested agent or amount, and caller insistence. Using these
      estimates, routine consultation of a regional poison center as part of EMS
      dispatch averted $486,595 in charges, and $183,279 in payments. CONCLUSIONS:
      Routine consultation of a poison center by emergency medical dispatchers can
      reduce unnecessary dispatches, ambulance transports, and ED visits with
      significant associated cost savings.

PMID- 27718163
TI  - Hydrocodone Bitartrate ER (Hysingla(r) ER): A Review in Chronic Pain.
AB  - Hydrocodone bitartrate extended-release (Hysingla(r) ER; referred to hereafter as
      hydrocodone ER) was the first single-entity hydrocodone formulation recognized by
      the US FDA as having abuse-deterrent properties. It is indicated for the
      management of pain severe enough to require daily, around-the-clock, long-term
      opioid treatment and for which alternative treatment options are inadequate. Once
      daily oral hydrocodone ER provides consistent plasma hydrocodone concentrations
      and sustained analgesia over the 24-h dosing interval. Its physicochemical
      properties render hydrocodone ER harder to manipulate physically, which is
      expected to deter intranasal, intravenous and oral abuse. For instance, oral
      hydrocodone ER (intact or chewed) significantly reduced drug liking relative to
      hydrocodone solution in a clinical study. In two large phase III studies in
      patients with chronic pain, hydrocodone ER reduced pain intensity, with its
      effects seen early (during dose titration) and maintained during <=76 weeks'
      treatment. During maintenance therapy, the majority of patients continued
      hydrocodone ER at the dosage achieved at the end of dose titration and without
      requiring increased doses of supplemental pain medication, suggesting adequate
      pain management. Hydrocodone ER was generally well tolerated, with a safety
      profile consistent with that seen with other MU-opioid analgesics. However, like
      other opioids, it is associated with risks of addiction, abuse/misuse and serious
      adverse events (AEs), including respiratory depression, withdrawal, physical
      dependence and overdose. Although large postmarketing studies are needed to
      determine whether the abuse-deterrent properties of hydrocodone ER result in
      meaningful reductions in abuse, misuse and related adverse clinical outcomes,
      current evidence indicates that hydrocodone ER is a useful treatment option for
      patients with chronic pain.

PMID- 27718166
TI  - The Checkered Divide.

PMID- 27718167
TI  - The University of Chicago Pritzker School of Medicine Poetry Contest.

PMID- 27718168
TI  - Independent or Integrated? The Impact on Subject Examination Scores of Changing a
      Neuropsychiatry Clerkship to Independent Clerkships in Psychiatry and Neurology.
AB  - OBJECTIVE: This study was undertaken to assess any impact on National Board of
      Medical Examiners (NBME) neurology and psychiatry subject examination scores of
      changing from an integrated neuropsychiatry clerkship to independent neurology
      and psychiatry clerkships. METHODS: NBME psychiatry and neurology subject
      examinations scores were compared for all 625 students completing the required
      neuropsychiatry clerkship in academic years 2005-2006 through 2008-2009 with all
      650 students completing the independent neurology and psychiatry clerkships in
      academic years 2009-2010 through 2012-2013. Statistical adjustments were made to
      ensure comparability across groups and over time. RESULTS: A significant
      improvement in subject examination scores was associated with the independent
      clerkships. CONCLUSIONS: The independent clerkship model was associated with a
      modest improvement in NBME subject examination scores. This finding may be
      attributable to many causes or combination of causes other than curricular
      design. Curricular planners need to pay attention to the potential impact of
      course integration on specialty-specific NBME subject examination performance.

PMID- 27718164
TI  - The Diagnostic and Prognostic Potential of microRNAs in Epithelial Ovarian
      Carcinoma.
AB  - Ovarian cancer causes more than 100,000 deaths globally per year. Despite
      intensive research efforts, there has been little improvement in the overall
      survival of patients over the past three decades. Most patients are not diagnosed
      until the cancer is at an advanced stage, by which time their chances of still
      being alive after 5 years are appallingly low. Attempts to extend life in these
      patients have been, for the most part, unsuccessful. This owes partly to the lack
      of suitable biomarkers for stratifying patients at the molecular level, into
      responders and non-responders. This would lead to more drugs being shown to have
      a clinical benefit and being approved for use in subgroups of patients. There is
      also a desperate need for improved biomarkers for earlier detection of ovarian
      cancer; if the disease is detected sooner there is a significantly improved
      outlook. In this review, we outline the evidence that microRNAs are deregulated
      in ovarian cancer, what this can tell us about tumour progression and how it
      could be used to improve patient stratification in clinical trials. We also
      describe the potential for circulating microRNAs, both associated with proteins
      or carried in vesicles, to be used as diagnostics for earlier detection or as
      biomarkers for informing clinicians on the prognosis and best treatment of
      ovarian cancer.

PMID- 27718165
TI  - Polymorphisms in MIR122, MIR196A2, and MIR124A Genes are Associated with Clinical
      Phenotypes in Inflammatory Bowel Diseases.
AB  - BACKGROUND: Inflammatory bowel diseases (IBDs), including Crohn's disease (CD)
      and ulcerative colitis (UC), are multifactorial disorders that result from a
      dysregulated inflammatory response to environmental factors in genetically
      predisposed individuals. Recently, microRNAs (miRNAs) have been shown to be
      involved in the development of IBDs. AIMS: We investigated common variants in
      five miRNA genes in a cohort of Italian IBD patients, to evaluate their possible
      role in the disease's susceptibility and phenotype manifestations. METHODS: The
      analysis included 267 CD patients, 207 UC patients, and 298 matched healthy
      controls. Polymorphisms in the MIR122, MIR499, MIR146A, MIR196A2, and MIR124A
      genes were evaluated by allelic discrimination assay. RESULTS: We did not find
      associations between mir polymorphisms and IBD susceptibility. In both diseases,
      rs17669 and rs11614913 (MIR122 and MIR196A2) seem to contribute to clinical
      phenotypes: ileal location in CD (odds ratio [OR] = 1.82, p = 0.03; OR = 0.51, p
      = 0.01), and left-sided extent in UC (OR = 0.43, p = 0.05; OR = 0.28, p = 0.002).
      In CD, the MIR124A polymorphism (rs531564) contributed to colon location (p =
      0.03, OR = 2.74). Finally, the variant allele of rs11614913 was associated with
      early age at onset in both diseases (p = 0.05 and p = 0.02). CONCLUSIONS: We
      showed for the first time that polymorphisms in MIR122, MIR196A2, and MIR124A
      could play a role in clinical phenotype modulation in IBD.

PMID- 27718169
TI  - Guiding Psychiatry Trainees on Their First Job Search.

PMID- 27718170
TI  - Modulation of cutaneous extracellular collagen contraction by phosphorylation
      status of p130Cas.
AB  - Skin can respond to various types of internal and/or external mechanostimuli,
      such as excessive tension caused by body growth or decompression due to weight
      loss, which significantly affect skin morphology. Mechanosensors, including
      p130Cas, are reported to play a role in deformation and subsequent recovery of
      various tissues including skeletal muscles and blood vessels. However, the role
      of mechanotransduction via p130Cas in the regulation of skin size remains
      unclear. In this report, p130Cas activation was manipulated using a fibroblast
      embedded collagen gel model or mouse skin contraction model. Inhibition or
      activation of Src family kinase-mediated phosphorylation of p130Cas significantly
      depressed and accelerated collagen gel contraction, respectively. The results
      also demonstrated age-dependent depression of cutaneous p130Cas activation in
      vivo. Inhibition of p130Cas signaling in our mouse model significantly suppressed
      recovery from cutaneous deformation. Taken together, our study highlighted the
      important role of p130Cas in cutaneous mechanotransduction for skin homeostasis.

PMID- 27718172
TI  - Characterization of paraffin based breast tissue equivalent phantom using a CdTe
      detector pulse height analysis.
AB  - In this study, paraffin was selected as a base material and mixed with different
      amounts of CaSO4.2H2O and H3BO3 compounds in order to mimic breast tissue. Slab
      phantoms were produced with suitable mixture ratios of the additives in the
      melted paraffin. Subsequently, these were characterized in terms of first half
      value layer (HVL) in the mammographic X-ray range using a pulse-height
      spectroscopic analysis with a CdTe detector. Irradiations were performed in the
      energy range of 23-35 kVp under broad beam conditions from Mo/Mo and Mo/Rh
      target/filter combinations. X-ray spectra were acquired with a CdTe detector
      without and with phantom material interposition in increments of 1 cm thickness
      and then evaluated to obtain the transmission data. The net integral areas of the
      spectra for the slabs were used to plot the transmission curves and these curves
      were fitted to the Archer model function. The results obtained for the slabs were
      compared with those of standard mammographic phantoms such as CIRS BR series
      phantoms and polymethylmethacrylate plates (PMMA). From the evaluated
      transmission curves, the mass attenuation coefficients and HVLs of some mixtures
      are close to those of the commercially available standard mammography phantoms.
      Results indicated that when a suitable proportion of H3BO3 and CaSO4.2H2O is
      added to the paraffin, the resulting material may be a good candidate for a
      breast tissue equivalent phantom.

PMID- 27718171
TI  - Update on Clinical Utility of Continuous Glucose Monitoring in Type 1 Diabetes.
AB  - Since the early 2000s, continuous glucose monitoring (CGM) technology has
      advanced to become a standard of care in the treatment of type 1 diabetes.
      Unfortunately, CGM use is not commonly integrated into practice. This article
      will review the history, technology, and need for systematic training in CGM.
      Additionally, it will review recent clinical trial data demonstrating the
      benefits that CGM offers to all people with type 1 diabetes and the clinicians
      who care for them.

PMID- 27718173
TI  - Neuroinflammation, immune system and Alzheimer disease: searching for the missing
      link.
AB  - Due to an increasingly aging population, Alzheimer disease (AD) represents a
      crucial issue for the healthcare system because of its widespread prevalence and
      the burden of its care needs. Several hypotheses on AD pathogenesis have been
      proposed and current therapeutical strategies have shown limited effectiveness.
      In the last decade, more evidence has supported a role for neuroinflammation and
      immune system dysregulation in AD. It remains unclear whether astrocytes,
      microglia and immune cells influence disease onset, progression or both. Amyloid
      beta peptides that aggregate extracellularly in the typical neuritic plaques
      generate a constant inflammatory environment. This causes a prolonged activation
      of microglial and astroglial cells that potentiate neuronal damage and provoke
      the alteration of the blood brain barrier (BBB), damaging the permeability of
      blood vessels. Recent data support the role of the BBB as a link between
      neuroinflammation, the immune system and AD. Hence, a thorough investigation of
      the neuroinflammatory and immune system pathways that impact neurodegeneration
      and novel exciting findings such as microglia-derived microvesicles,
      inflammasomes and signalosomes will ultimately enhance our understanding of the
      pathological process. Eventually, we should proceed with caution in defining a
      causal or consequential role of neuroinflammation in AD, but rather focus on
      identifying its exact pathological contribution.

PMID- 27718174
TI  - The Use of Tranexamic Acid in Sleeve Gastrectomy.

PMID- 27718175
TI  - Robotic Near-Total Pancreatectomy for Nesidioblastosis after Bariatric Surgery.
AB  - Postprandial symptoms of neuroglycopenia after bariatric surgery may result as a
      consequence of endogenous hyperinsulinemic hypoglycemia (nesidioblastosis) not
      dumping syndrome. Pancreatectomy is an acceptable treatment for this condition.
      We present the video of a case of near-total distal robotic pancreactectomy for
      the treatment of nesidioblastosis after Roux-en-Y gastric bypass. Robotic
      pancreatectomy is an alternative to the treatment of nesidioblastosis after Roux
      en-Y gastric bypass.

PMID- 27718176
TI  - LSG vs OAGB-1 Year Follow-up Data-a Randomized Control Trial.
AB  - OBJECTIVES: Laparoscopic sleeve gastrectomy (LSG) is one of the most popular
      bariatric procedure. One anastomosis gastric bypass (OAGB) is rapidly emerging as
      a safe and effective metabolic procedure. This study aims at comparing the 1-year
      follow-up results of OAGB and LSG in terms of excess weight loss, complications,
      resolution of comorbidities, and quality of life. METHODS: A prospective
      randomized study of results between 100 LSG and 101 OAGB patients was done from
      2012 to 2015. The results were compared regarding operative outcomes, percentage
      of excess weight loss, complications, resolution of comorbidities, and quality of
      life (BAROS score). RESULTS: The mean BMI for the OAGB and LSG group was 44.31
      and 43.75 kg/m2, respectively. Percentage of excess weight loss (%EWL) for OAGB
      vs LSG was 66.87 +/- 10.87 vs 63.97 +/- 13.24 at 1 year (p > 0.05), respectively.
      Diabetes remission was 83.63 % in OAGB patients and 76.58 % in LSG patients.
      Remission of hypertension is 64.15 % in OAGB patients and 66.07 % in LSG
      patients. Bariatric Analysis Reporting and Outcome System (BAROS) was 3.71 in LSG
      and 3.96 in OAGB. CONCLUSIONS: In our study, there was no significant difference
      between LSG and OAGB in outcome at 1 year follow-up in % excess weight loss,
      remission of HTN, and quality of life. OAGB has marginally better outcome in T2
      DM remission. However, a longer follow-up is required to establish a correct
      comparative result.

PMID- 27718177
TI  - A Novel Endoscopic Bariatric Procedure: Results of an Experimental Study.
AB  - BACKGROUND: Surgical treatment of obesity is characterized by both early and late
      complications, and thus, there is a need to develop safe and non-invasive
      techniques. Ghrelin is an orexigenic hormone produced by the fundus of the
      stomach, which may represent a novel target for obesity management.
      Unfortunately, numerous attempts to alter ghrelin levels have failed to present
      significant clinical results. We describe a novel procedure that involves
      modifying arterial blood flow to the gastric fundus for limiting plasma ghrelin
      levels. METHODS: A gastroscope was advanced into the gastric fundus of 13 healthy
      Yorkshire swine, and the fundus was clipped under direct visualization to
      restrict left gastric artery blood flow. Body weights and ghrelin levels were
      recorded before and once a week for 4 weeks after the procedure. RESULTS:
      Compared to controls, gastroscopic clipping of the fundus decreased plasma
      ghrelin levels and prevented further weight gain in the 4 weeks of follow-up.
      Immunohistochemistry and histomorphometry revealed reduced numbers of ghrelin
      positive cells in the fundus of experimental animals. We also observed thrombosis
      in submucosal arteries and submucosal fibrosis. Histological studies demonstrated
      minimal gastric mucosal injury. CONCLUSION: Gastroscopic clipping of the fundus
      in an experimental porcine model resulted in sustained weight loss and a
      reduction in plasma ghrelin levels at 1 month post-procedure, with no adverse
      events. Further experimental studies in human patients are needed to examine the
      clinical utility of this procedure and to optimize a technique, which can
      facilitate adequate weight loss while minimizing the risk of mucosal injury.

PMID- 27718178
TI  - QT Interval Shortening After Bariatric Surgery Depends on the Applied Heart Rate
      Correction Equation.
AB  - BACKGROUND: A shortening of electrocardiographic QT interval has been observed in
      obese subjects after weight loss, but previous results may have been biased by
      inappropriate heart rate (HR) correction. METHODS: Electrocardiography (ECG)
      recordings of 49 (35 females) severely obese patients before and 12 months after
      Roux-en-Y gastric bypass (RYGB) surgery were analysed. QT interval (QTc) was
      calculated by using four different equations, i.e. Bazett, Fridericia, Framingham
      and Hodges. RESULTS: Irrespectively of the used correction formula, QTc interval
      length was reduced after the surgery (QTcBazett -31 +/- 18 ms; QTcFridericia -12
      +/- 15 ms; QTcFramingham -14 +/- 15 ms; QTcHodges -9 +/- 15 ms; all Ps < 0.001),
      but QTcBazett reduction was significantly greater than the reduction in QTc
      calculated upon the other three equations (all Ps < 0.001). Moreover, changes in
      QTcBazett (P < 0.001) but not in QTcFridericia, QTcFramingham and QTcHodges (all
      Ps > 0.05) were significantly correlated with concurrent changes in HR.
      Multivariate regression analyses revealed a significant independent association
      of serum insulin levels with QTcFridericia, QTcFramingham and QTcHodges values
      (all Ps < 0.05) preoperatively, whilst changes in QTc interval length after the
      surgery were not consistently associated to concurrent changes in metabolic
      traits. CONCLUSIONS: Our data show that the extent of weight loss-associated QTc
      interval shortening largely depends on the applied HR correction equation and
      appears to be overestimated when the most popular Bazett's equation is used.

PMID- 27718179
TI  - Assessment of Folate Status in Obese Patients: Should We Measure Folate in Serum
      or in Red Blood Cells?
AB  - BACKGROUND: Recent studies revealed that obesity is associated with decreased
      serum but at the same time increased red blood cell (RBC) folate concentrations
      compared with lean subjects, thus casting doubt upon the agreement between serum
      and RBC folate measurements for assessing folate status. This work aimed to
      determine whether these two metrics lead to the same classification of folate
      status in obese patients. METHODS: RBC and serum folate concentrations were
      measured with a chemiluminescent immunoassay in 263 adults with body mass index
      >=30 kg/m2 and without previous bariatric surgery. Among them, 68.1 % were
      eligible for bariatric surgery. Each serum and RBC folate result was classified
      as deficient or not according to thresholds recommended by the kit manufacturer
      (model A) or by the World Health Organization (model B). The agreement between
      serum and RBC folate results was evaluated using the proportion of overall
      agreement and the prevalence-adjusted bias-adjusted kappa (PABAK) statistics.
      RESULTS: The overall percentage agreements between serum and RBC measurements
      were 91.6 % (95 % CI 87.6-94.7 %) and 92.4 % (95 % CI 88.5-95.3 %) with PABAK
      coefficients of 0.87 (95 % CI 0.82-0.93) and 0.88 (95 % CI 0.83-0.94) in the
      models A and B, respectively, corresponding to almost perfect agreement. The same
      was true in the subgroup of patients eligible for bariatric surgery. Gender, age,
      and BMI did not influence the quality of agreement between the two parameters.
      CONCLUSIONS: The present study showed that folate measurements in serum and in
      RBC display similar performances to assess folate status in obese patients.

PMID- 27718180
TI  - Linking bronchopulmonary dysplasia to adult chronic lung diseases: role of WNT
      signaling.
AB  - Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases
      in infants caused by pre- and/or postnatal lung injury. BPD is characterized by
      arrested alveolarization and vascularization due to extracellular matrix
      remodeling, inflammation, and impaired growth factor signaling. WNT signaling is
      a critical pathway for normal lung development, and its altered signaling has
      been shown to be involved in the onset and progression of incurable chronic lung
      diseases in adulthood, such as chronic obstructive pulmonary disease (COPD) or
      idiopathic pulmonary fibrosis (IPF). In this review, we summarize the impact of
      WNT signaling on different stages of lung development and its potential
      contribution to developmental lung diseases, especially BPD, and chronic lung
      diseases in adulthood.

PMID- 27718182
TI  - Overview of Vaccine Adjuvants: Introduction, History, and Current Status.
AB  - Adjuvants are included in sub-unit or recombinant vaccines to enhance the potency
      of poorly immunogenic antigens. Adjuvant discovery is as complex as it is a
      multidiscplinary intersection of formulation science, immunology, toxicology, and
      biology. Adjuvants such as alum, which have been in use for the past 90 years,
      have illustrated that adjuvant research is a methodical process. As science
      advances, new analytical tools are developed which allows us to delve deeper into
      the various mechanisms that generates a potent immune response. Additionally,
      these new techniques help the field learn about our existing vaccines and what
      makes them safe, and effective, allowing us to leverage that in the next
      generation of vaccines. Our goal in this chapter is to define the concept, need,
      and mechanism of adjuvants in the vaccine field while describing its history,
      present use, and future prospects. More details on individual adjuvants and their
      formulation, development, mechanism, and use will be covered in depth in the next
      chapters.

PMID- 27718183
TI  - Development of the CpG Adjuvant 1018: A Case Study.
AB  - The development of aluminum salts (alum) as vaccine adjuvants was an empirical
      process with little understanding of the mechanism of action and, with decades of
      use, it has become clear that there is a need for alternatives where alum-based
      adjuvants are suboptimal. Oligonucleotides containing unmethylated CpG sequences
      represent one alternative as they are potent stimulators of the vertebrate innate
      immune system through activation of Toll-like receptor-9. This chapter outlines
      the methods used by Dynavax Technologies to progress a CpG-containing
      oligonucleotide sequence termed 1018 through preclinical and clinical testing as
      an adjuvant for immunization against hepatitis B virus (HBV). 1018 is a short (22
      mer) oligonucleotide sequence containing CpG motifs active in both rodents and
      primates. Preclinical testing of hepatitis B surface antigen (HBsAg) + 1018 in
      comparison to HBsAg + alum demonstrated induction of substantially higher
      antibody titers and a favorable safety profile for 1018. Most importantly,
      clinical studies with HBsAg vaccination consistently demonstrate more rapid
      induction of protective antibody titers with 1018 compared to alum in all
      populations studied, including groups that are harder to immunize such as the
      elderly and immunocompromised individuals. These studies represent the basis for
      use of the CpG-motif-containing oligonucleotide 1018 as an improved adjuvant for
      HBsAg immunogenicity. HBsAg + 1018 (HEPLISAV-BTM) is currently in late-stage
      clinical testing for prophylactic immunization against HBV.

PMID- 27718184
TI  - Syntheses of Human TLR8-Specific Small-Molecule Agonists.
AB  - Human toll-like receptor (hTLR)-8 is expressed in myeloid dendritic cells,
      monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists
      evokes a distinct cytokine profile which favors the development of type 1 helper
      T cells. Focused exploration of structure-activity relationships in the
      imidazoquinolines has led to the identification of several novel human TLR8
      specific agonists. The synthetic procedures for best-in-class analogues
      encompassing four chemotypes are described.

PMID- 27718186
TI  - QS-21 Adjuvant: Laboratory-Scale Purification Method and Formulation Into
      Liposomes.
AB  - QS-21, a saponin extracted from the tree Quillaja saponaria Molina, is a vaccine
      adjuvant which has been shown to elicit robust antibody and cell-mediated immune
      responses in a variety of preclinical and clinical studies [1]. Its purification
      from the natural source is a lengthy and difficult process. The commercially
      available saponin mixture Quil-A(r) is a fraction of the bark extract containing
      a variety of saponins, including QS-21. In order to facilitate access to QS-21 at
      laboratory-scale amounts, we propose here a method of purification of QS-21
      starting from Quil-A(r). In addition, we describe a protocol to appropriately
      formulate QS-21 into cholesterol-containing, neutral liposomes which are known to
      decrease QS-21's hemolytic activity while retaining the adjuvant effect. Methods
      for the physicochemical characterization of purified QS-21 and of the QS
      21/liposome formulations are also described.

PMID- 27718181
TI  - Uterine Adenosarcoma: a Review.
AB  - Adenosarcomas are rare malignancies of the female genital tract, accounting for
      approximately 5 % of uterine sarcomas. Occasionally, adenosarcoma occurs in the
      ovaries or in extra-uterine tissue, which may be related to endometriosis. These
      tumors are characterized by benign epithelial elements and a malignant
      mesenchymal component. Pathologic diagnosis is dependent on the identification of
      the characteristic morphologic features. The most common immunohistochemical
      markers for adenosarcoma are CD10 and WT1, but these are not specific. The most
      frequent presenting symptom is abnormal uterine bleeding. The majority of
      patients present with stage I disease, with a 5-year overall survival of 60 to 80
      %. Survival is influenced by the presence of myometrial invasion, sarcomatous
      overgrowth, lymphovascular invasion, necrosis, and the presence of heterologous
      elements including rhabdomyoblastic differentiation. Patients with sarcomatous
      overgrowth have significantly increased risk of recurrence 23 versus 77 % and
      decreased 5-year overall survival 50 to 60 %. Standard of care treatment is total
      hysterectomy with bilateral salpingo-oophorectomy without lymphadenectomy, as the
      incidence of lymph node metastasis is rare. Retrospective data does not support
      the use of adjuvant pelvic radiotherapy in uterine adenosarcomas as no survival
      benefit is seen. Insufficient data exists to recommend routinely neoadjuvant or
      adjuvant chemotherapy for uterine adenosarcomas. Limited evidence exists for the
      role of hormonal therapy in uterine adenosarcomas. The PIK3/AKT/PTEN pathway is
      mutated in ~70 % of adenosarcomas, and this may represent a possible therapeutic
      target. This article reviews the current state of knowledge concerning uterine
      adenosarcoma and discusses the management of this rare tumor.

PMID- 27718187
TI  - Purification of an Immunoadjuvant Saponin Fraction from Quillaja brasiliensis
      Leaves by Reversed-Phase Silica Gel Chromatography.
AB  - Saponins include a large variety of molecules that find several applications in
      pharmacology. The use of Quillaja saponaria saponins as immunological adjuvants
      in vaccines is of interest due to their capacity to stimulate both humoral and
      cellular responses. The congener species Q. brasiliensis has saponins with
      chemical similarities and adjuvant activity comparable to that of Q. saponaria
      fraction Quil-A(r), with additional advantages of showing lower toxicity and
      reduced hemolytic activity. Here we describe in detail the methods for preparing
      the aqueous extract from Q. brasiliensis leaves, as well as the purification of
      the bioactive saponin fraction QB-90 using silica reversed-phase chromatography.

PMID- 27718185
TI  - Semisynthesis of Analogues of the Saponin Immunoadjuvant QS-21.
AB  - Saponins are triterpene glycoside natural products that exhibit many different
      biological properties, including activation and modulation of the immune system,
      and have therefore attracted significant interest as immunological adjuvants for
      use in vaccines. QS-21 is the most widely used and promising saponin adjuvant but
      suffers from several liabilities, such as scarcity, dose-limiting toxicity, and
      hydrolytic instability. Chemical synthesis has emerged as a powerful approach to
      obtain homogeneous, pure samples of QS-21 and to improve its properties and
      therapeutic profile by providing access to optimized, synthetic saponin variants.
      Herein, we describe a general method for the semisynthesis of these molecules
      from QS-21, with detailed synthetic protocols for two saponin variants developed
      in our recent work.

PMID- 27718188
TI  - Biosynthetic Approaches to Squalene Production: The Case of Yeast.
AB  - Squalene is a precursor in the eukaryotic sterol biosynthesis. It is a valuable
      compound with several human health-related applications. Since the traditional
      natural resources of squalene are limited, alternatives for the production of
      squalene on industrial scale have been intensively explored during past years.
      The yeast Saccharomyces cerevisiae represents an attractive option due to
      elaborated techniques of genetic and metabolic engineering that can be applied to
      improve squalene yields. We discuss in this chapter some theoretical aspects of
      genetic manipulations of the ergosterol biosynthesis pathway aimed at increased
      squalene production and describe analytical methods for squalene purification and
      determination of its content in yeast cells.

PMID- 27718189
TI  - In Silico Adjuvant Design and Validation.
AB  - Adjuvants are substances that boost the protective immune response to vaccine
      antigens. The majority of known adjuvants have been identified through the use of
      empirical approaches. Our aim was to identify novel adjuvants with well-defined
      cellular and molecular mechanisms by combining a knowledge of immunoregulatory
      mechanisms with an in silico approach. CD4+CD25+FoxP3+ regulatory T cells (Tregs)
      inhibit the protective immune responses to vaccines by suppressing the activation
      of antigen presenting cells such as dendritic cells (DCs). In this chapter, we
      describe the identification and functional validation of small molecule
      antagonists to CCR4, a chemokine receptor expressed on Tregs. The CCR4 binds the
      chemokines CCL22 and CCL17 that are produced in large amounts by activated innate
      cells including DCs. In silico identified small molecule CCR4 antagonists
      inhibited the migration of Tregs both in vitro and in vivo and when combined with
      vaccine antigens, significantly enhanced protective immune responses in
      experimental models.

PMID- 27718190
TI  - Manufacturing Methods for Liposome Adjuvants.
AB  - A wide range of studies have shown that liposomes can act as suitable adjuvants
      for a range of vaccine antigens. Properties such as their amphiphilic character
      and biphasic nature allow them to incorporate antigens within the lipid bilayer,
      on the surface, or encapsulated within the inner core. However, appropriate
      methods for the manufacture of liposomes are limited and this has resulted in
      issues with cost, supply, and wider scale application of these systems. Within
      this chapter we explore manufacturing processes that can be used for the
      production of liposomal adjuvants, and we outline new manufacturing methods can
      that offer fast, scalable, and cost-effective production of liposomal adjuvants.

PMID- 27718191
TI  - Synthesis of Lymph Node-Targeting Adjuvants.
AB  - Molecular adjuvants based off of pattern recognition receptor agonists are
      capable of potently stimulating innate immunity and inducing protective immune
      responses to subunit antigens. One significant disadvantage to these small
      molecule adjuvants is their pharmacokinetic profile of entering the blood stream
      rather than the lymphatics after parental injection. In order to target molecular
      adjuvants to lymph nodes, we have developed nanoparticle carriers whose size has
      been optimized to avoid the blood and efficiently drain to lymph nodes (Hanson et
      al. Vaccine 33:861-8,2015; Hanson et al. J Clin Invest 125:2532-2546, 2015). This
      chapter describes in detail the materials and procedures necessary to synthesize
      liposome nanoparticle carriers of either hydrophobic or hydrophilic adjuvants,
      including synthesis tips, alternative equipment options, and pitfalls to avoid.

PMID- 27718192
TI  - Preparing an Adjuvanted Thermoresponsive Gel Formulation for Sublingual
      Vaccination.
AB  - Thermoresponsive gels have unique physicochemical properties that may enable more
      effective mucosal delivery of active compounds. The thermoresponsive gel (TRG)
      formulation developed by our group for sublingual delivery maintains fluid-like
      liquid properties at 2  degrees C-8  degrees C and forms a gel at the
      physiological temperature (~37  degrees C) within a few seconds. Here, we
      describe the preparation of a thermoresponsive gel vaccine formulation. Our
      preclinical studies with various antigens suggest that the mucoadhesive,
      adjuvanted TRG formulation enabled increased contact of the vaccine antigen with
      the mucosa, resulting in increased mucosal response(s) with a potential for
      antigen dose reduction.

PMID- 27718193
TI  - Manufacture of Oil-in-Water Emulsion Adjuvants.
AB  - Emulsion adjuvants for human vaccines have evolved gradually over the last
      century. Current formulations are the result of many refinements to their
      composition and manufacturing, as well as optimization for safety and efficacy.
      Squalene has emerged as being particularly suitable for the manufacturing of safe
      oil-in-water (O/W) adjuvants for parenteral applications due to its
      biocompatibility and ability to be metabolized. Emulsion particle size has been
      identified as an important parameter affecting the pharmaceutical performance of
      O/W emulsion adjuvants. Submicronic emulsions with sizes in the 80-200 nm range
      are preferred for potency, manufacturing consistency, and stability reasons. Two
      manufacturing processes, high pressure homogenization (HPH or microfluidization)
      and a phase inversion temperature method (PIT), are described to yield such fine
      and long-term stable emulsion adjuvants.

PMID- 27718194
TI  - Methods to Prepare Aluminum Salt-Adjuvanted Vaccines.
AB  - Many human vaccines contain certain insoluble aluminum salts such as aluminum
      oxyhydroxide and aluminum hydroxyphosphate as vaccine adjuvants to boost the
      immunogenicity of the vaccines. Aluminum salts have been used as vaccine
      adjuvants for decades and have an established, favorable safety profile. However,
      preparing aluminum salts and aluminum salt-adjuvanted vaccines in a consistent
      manner remains challenging. This chapter discusses methods to prepare aluminum
      salts and aluminum salt-adjuvanted vaccines, factors to consider during
      preparation, and methods to characterize the vaccines after preparation.

PMID- 27718195
TI  - Production of Adjuvant-Loaded Biodegradable Particles for Use in Cancer Vaccines.
AB  - Immune adjuvants, such as ligands for pathogen-associated molecular patterns
      (PAMPs), have been showing promise in boosting immune responses to tumor
      associated antigens, and delivering these adjuvants as discrete packages is
      considered advantageous over delivery in soluble form. Here we describe in
      detail, methods for independently loading a range of adjuvants into polymer-based
      biodegradable particles. We also describe the means by which to characterize
      these particles with respect to adjuvant loading and release kinetics as well as
      in terms of particle size, shape, and zeta-potential. These adjuvant-loaded
      particles have the potential to be used in dendritic cell-based uptake
      experiments performed in vitro or to be used in preclinical cancer vaccine
      research applications where they can be co-delivered with antigen-loaded
      particles or some other vaccine component comprising antigenic material.

PMID- 27718196
TI  - Lyophilization of Adjuvanted Vaccines: Methods for Formulation of a Thermostable
      Freeze-Dried Product.
AB  - Lyophilization of vaccines is advantageous for the distribution and storage of
      thermally labile products, particularly in regions where cold chain management is
      difficult. To date, current lyophilized vaccines do not contain an adjuvant.
      Instead, adjuvanted vaccines may be presented as a two vial system, that require
      bedside-mixing prior to immunization. Here we present an example of a
      lyophilization cycle that we have used to successfully freeze-dry an adjuvanted
      protein formulation in a single vial.

PMID- 27718197
TI  - Stressed Stability Techniques for Adjuvant Formulations.
AB  - Stressed stability testing is crucial to the understanding of mechanisms of
      degradation and the effects of external stress factors on adjuvant stability.
      These studies vastly help the development of stability indicating tests and the
      selection of stabilizing conditions for long term storage. In this chapter, we
      provide detailed protocols for the execution of forced degradation experiments
      that evaluate the robustness of adjuvant formulations against thermal,
      mechanical, freeze-thawing, and photo stresses.

PMID- 27718198
TI  - Particle Sizing of Nanoparticle Adjuvant Formulations by Dynamic Light Scattering
      (DLS) and Nanoparticle Tracking Analysis (NTA).
AB  - Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) are two
      orthogonal and complementary methods of measuring size of particles in a sample.
      These technologies use the theory of Brownian motion by analyzing the random
      changes of light intensity scattered by particles in solution. Both techniques
      can be used to characterize particle size distribution of proteins and
      formulations in the nanometer to low micron range.Each method has benefits over
      the other. DLS is a quick and simple measurement that is ideal for monodisperse
      particles and can also analyze a distribution of particles over a wide range of
      sizes. NTA provides a size distribution that is less susceptible to the influence
      of a few large particles, and has the added benefit of being able to measure
      particle concentration. Here we describe methods for measuring the particle size
      and concentration of an oil-in-water nanoemulsion.

PMID- 27718199
TI  - Quantification of Multiple Components of Complex Aluminum-Based Adjuvant Mixtures
      by Using Fourier Transform Infrared Spectroscopy and Partial Least Squares
      Modeling.
AB  - Fourier transform infrared (FTIR) spectroscopy is widely used in the
      pharmaceutical industry for process monitoring, compositional quantification, and
      characterization of critical quality attributes in complex mixtures. Advantages
      over other spectroscopic measurements include ease of sample preparation,
      quantification of multiple components from a single measurement, and the ability
      to quantify optically opaque samples. This method describes the use of a
      multivariate model for quantifying a TLR4 agonist (GLA) adsorbed onto aluminum
      oxyhydroxide (Alhydrogel(r)) using FTIR spectroscopy that may be adapted to
      quantify other complex aluminum based adjuvant mixtures.

PMID- 27718200
TI  - Determination of Protein Content in Alhydrogel(r)-Based Vaccines by O
      Phthalaldehyde Assay.
AB  - The quantification of antigens adsorbed to aluminum-based adjuvants (alum)
      typically involves a method that first extracts antigen from the alum followed by
      the quantification of the antigen available in the extract. Extraction procedures
      often result in less than 100 % desorption of the antigen from the alum adjuvant
      and may alter the conformation of the antigen, reducing the accuracy of the
      subsequent method used for quantification. There is no generic method available
      for directly assessing the protein content when formulated on alum. Here we offer
      a method that can directly quantify protein adsorbed to Alhydrogel(r) using a
      simple fluorescence assay that is highly accurate and reproducible for
      Alhydrogel(r) formulations containing 25-400 MUg/mL of antigen.

PMID- 27718201
TI  - Staining and Transfer Techniques for SDS-PAGE Gels to Minimize Oil-in-Water
      Emulsion Adjuvant Interference.
AB  - Adjuvants in modern vaccines boost and shape immune responses and allow for
      antigen dose-sparing. Analysis of protein antigens in the presence of adjuvants
      can prove challenging, especially if the adjuvant interferes with visualization
      of the protein band on an SDS-PAGE gel. In this chapter, a variety of different
      techniques are presented to mitigate the interference of a nanoemulsion adjuvant,
      GLA-SE, with different recombinant proteins of varying molecular weight by
      addressing sample preparation and staining methods.

PMID- 27718202
TI  - Interactions Between Antigens and Nanoemulsion Adjuvants: Separation and
      Characterization Techniques.
AB  - Determining the association of vaccine components in a formulation is of interest
      for designing and optimizing well characterized vaccines. Three methods are
      described to assess interactions between protein antigens and oil-in-water
      nanoemulsion adjuvants. The methods include (1) ultracentrifugation to measure
      free versus adjuvant-associated protein, (2) size exclusion chromatography (SEC)
      to qualitatively assess existing interactions, and (3) Native PAGE as a means to
      visualize the formulation run in its native state on a polyacrylamide gel. As
      with many techniques, the methods alone are not definitive, but data from
      multiple orthogonal assays can provide a more complete picture of protein
      adjuvant interactions.

PMID- 27718203
TI  - Screening Vaccine Formulations in Fresh Human Whole Blood.
AB  - Monitoring the immunological functionality of vaccine formulations is critical
      for vaccine development. While the traditional approach using established animal
      models has been relatively effective, the use of animals is costly and
      cumbersome, and animal models are not always reflective of a human response. The
      development of a human-based approach would be a major step forward in
      understanding how vaccine formulations might behave in humans. Here, we describe
      a platform methodology using fresh human whole blood (hWB) to monitor adjuvant
      modulated, antigen-specific responses to vaccine formulations, which is amenable
      to analysis by standard immunoassays as well as a variety of other analytical
      techniques.

PMID- 27718204
TI  - Analysis of the Innate Response to Adjuvants: Characterization of the Draining
      Lymph Node by Fluorescence-Activated Cell Sorting.
AB  - A clear index for a response to adjuvants is a change in the cellular composition
      of lymph nodes draining the site of adjuvant injection (Didierlaurent et al., J
      Immunol 183:6186-6197, 2009; Caproni et al., J Immunol 188:3088-98, 2012; Desbien
      et al., Eur J Immunol 1-11, 2014). During the steady state, lymph nodes (LNs) are
      composed of a fixed ratio of innate and adaptive cells awaiting activation
      signals from tissue draining lymph. Upon exposure to innate stimulants, lymph
      nodes undergo dramatic changes. The most apparent change to the lymph node is an
      increase in size. Antigen-independent activation of naive T cells and B cells, as
      a consequence of type I interferon signaling, results in upregulation of CD69
      (Sun and Zhang, J. Exp. Med 188:2335-2342, 1998), causing increased retention of
      cells in the lymph node and transient lymphopenia in the blood (Shiow et al.,
      Nature 440:540-544, 2006). In addition tissue-resident dendritic cells,
      macrophages, as well as circulating inflammatory monocytes will migrate into
      draining LNs and display maturation markers associated with activation. Such
      features can provide powerful discrimination of adjuvant potencies.

PMID- 27718205
TI  - Assessment of Antigen-Specific Cellular Immunogenicity Using Intracellular
      Cytokine Staining, ELISpot, and Culture Supernatants.
AB  - Quantification of cytokine production by CD4 and CD8 T cells after in vitro
      recall stimulation with the immunizing antigen is a powerful approach to
      characterize the cellular immune responses to immunization. Here we describe
      three complementary methods for such quantification including flow cytometric
      analysis of cytokine production by intracellular staining, ELISpot determination
      of the numbers of cytokine-producing cells, and generation of secreted cytokines
      and chemokines in culture supernatants for analysis by ELISA and/or cytometric
      bead arrays.

PMID- 27718207
TI  - Molecular Methods and Bioinformatic Tools for Adjuvant Characterization by High
      Throughput Sequencing.
AB  - Adjuvants in vaccine formulations are designed to enhance immune responses
      against a target antigen or pathogen. The ability of these vaccines to induce
      activation and differentiation of mature naive B cells to produce pathogen
      specific antibodies (immunoglobulins; Ig) helps guarantee long-lived humoral
      immunity. This process involves clonal expansion of antigen-specific B cells,
      genomic rearrangement of Ig heavy (IgH) and light (IgL) loci, somatic
      hypermutation (SHM), and clonal selection for affinity-matured antibody,
      resulting in a vast but directed repertoire of B cells expressing highly specific
      antibody proteins. High-throughput sequencing of the IgH and IgL complementary
      determining regions (CDRs) derived from various B cell populations provides an
      unprecedented way to observe dynamic responses of the humoral immune repertoire
      in response to vaccination. However, applying high-throughput sequencing (HTS)
      methodologies to multi-armed in vivo experiments requires careful coordination of
      sample preparation with downstream bioinformatics, particularly with regard to
      issues of quantitation, sequence fidelity, bar-coding, and multiplexing
      strategies. Here, we overview strategies of high-throughput sequencing and
      analysis of the adaptive immune complex loci applied to multi-armed, multiplexed
      experiments.

PMID- 27718206
TI  - Eliciting Epitope-Specific CD8+ T Cell Response by Immunization with Microbial
      Protein Antigens Formulated with alpha-Galactosylceramide: Theory, Practice, and
      Protocols.
AB  - CD8+ cytotoxic T lymphocytes confer protection against infectious diseases caused
      by viruses, bacteria, and parasites. Hence, significant efforts have been
      invested into devising ways to generate CD8+ T cell-targeted vaccines. Generation
      of microbe-free protein subunit vaccines requires a thorough knowledge of
      protective target antigens. Such antigens are proteolytically processed peptides
      presented by MHC class I molecules. To induce a robust antigen-specific CD8+ T
      cell response through vaccination, it is essential to formulate the antigen with
      an effective adjuvant. Here, we describe a versatile method for generating high
      frequency antigen-specific CD8+ T cells through immunization of mice using the
      invariant natural killer T cell agonist alpha-galactosylceramide as the adjuvant.

PMID- 27718208
TI  - Caricature generalization benefits for faces learned with enhanced idiosyncratic
      shape or texture.
AB  - Recent findings show benefits for learning and subsequent recognition of faces
      caricatured in shape or texture, but there is little evidence on whether this
      caricature learning advantage generalizes to recognition of veridical
      counterparts at test. Moreover, it has been reported that there is a relatively
      higher contribution of texture information, at the expense of shape information,
      for familiar compared to unfamiliar face recognition. The aim of this study was
      to examine whether veridical faces are recognized better when they were learned
      as caricatures compared to when they were learned as veridicals-what we call a
      caricature generalization benefit. Photorealistic facial stimuli derived from a 3
      D camera system were caricatured selectively in either shape or texture by 50 %.
      Faces were learned across different images either as veridicals, shape
      caricatures, or texture caricatures. At test, all learned and novel faces were
      presented as previously unseen frontal veridicals, and participants performed an
      old-new task. We assessed accuracies, reaction times, and face-sensitive event
      related potentials (ERPs). Faces learned as caricatures were recognized more
      accurately than faces learned as veridicals. At learning, N250 and LPC were
      largest for shape caricatures, suggesting encoding advantages of distinctive
      facial shape. At test, LPC was largest for faces that had been learned as texture
      caricatures, indicating the importance of texture for familiar face recognition.
      Overall, our findings demonstrate that caricature learning advantages can
      generalize to and, importantly, improve recognition of veridical versions of
      faces.

PMID- 27718210
TI  - Renin-angiotensin system in vertebrates: phylogenetic view of structure and
      function.
AB  - Renin substrate, biological renin activity, and/or renin-secreting cells in
      kidneys evolved at an early stage of vertebrate phylogeny. Angiotensin (Ang) I
      and II molecules have been identified biochemically in representative species of
      all vertebrate classes, although variation occurs in amino acids at positions 1,
      5, and 9 of Ang I. Variations have also evolved in amino acid positions 3 and 4
      in some cartilaginous fish. Angiotensin receptors, AT1 and AT2 homologues, have
      been identified molecularly or characterized pharmacologically in nonmammalian
      vertebrates. Also, various forms of angiotensins that bypass the traditional
      renin-angiotensin system (RAS) cascades or those from large peptide substrates,
      particularly in tissues, are present. Nonetheless, the phylogenetically important
      functions of RAS are to maintain blood pressure/blood volume homeostasis and ion
      fluid balance via the kidney and central mechanisms. Stimulation of cell growth
      and vascularization, possibly via paracrine action of angiotensins, and the
      molecular biology of RAS and its receptors have been intensive research foci.
      This review provides an overview of: (1) the phylogenetic appearance, structure,
      and biochemistry of the RAS cascade; (2) the properties of angiotensin receptors
      from comparative viewpoints; and (3) the functions and regulation of the RAS in
      nonmammalian vertebrates. Discussions focus on the most fundamental functions of
      the RAS that have been conserved throughout phylogenetic advancement, as well as
      on their physiological implications and significance. Examining the biological
      history of RAS will help us analyze the complex RAS systems of mammals.
      Furthermore, suitable models for answering specific questions are often found in
      more primitive animals.

PMID- 27718209
TI  - Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis
      Model.
AB  - Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that
      altering certain bacterial populations present in the gut may lead to a
      proinflammatory condition, that could result in the development of multiple
      sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course
      of MS. In this study, it has been aimed to relate all these variables starting
      from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP)
      with the determination of parameters related to oxidative stress in the blood,
      brain and spinal cord. For this purpose, samples obtained from EAE rats and
      relapsing-remitting (RRMS) MS patients were used. In addition, EAE rats were
      treated with Natalizumab, N-acetyl-cysteine and dimethyl fumarate. Natalizumab
      was also employed in RRMS. The results of this study revealed an improvement in
      the clinical symptoms of the EAE and MS with the treatments, as well as a
      reduction in the oxidative stress parameters and in LBP. Correlations between the
      clinical variables of the disease, i.e. oxidative damage and LBP, were
      established. Although the conclusions of this research are indeed relevant,
      further investigation would be necessary to establish the intrinsic mechanisms of
      the MS-oxidative stress-microbiota relationship.

PMID- 27718212
TI  - Table of Phenylalanine Content of Foods: Comparative Analysis of Data Compiled in
      Food Composition Tables.
AB  - BACKGROUND: Knowing the phenylalanine (Phe) content of foods is essential for
      managing the diet of patients with phenylketonuria. Data on the Phe content of
      foods are scarce and sometimes vary between different Food Composition Tables
      (FCT). Brazil created its own table of the Phe contents of fruits and vegetables
      based exclusively on the chemical analysis of protein content, considering that
      proteins contain 3-4% Phe (TCFA/ANVISA). This study compared the protein and Phe
      contents of vegetables and fruits provided by the TCFA/ANVISA with those listed
      in international food composition tables. METHODS: The Phe content of 71 fruits
      and vegetables listed in TCFA/ANVISA was classified into four subgroups, and the
      Wilcoxon nonparametric test compared the Phe and mean protein contents provided
      by the FCTs. All tests considered the bilateral hypothesis, and the level of
      significance was set at 5%. The Spearman's correlation coefficient measured the
      statistical dependence between Phe and protein contents. RESULTS: The mean Phe
      content was <50 mg Phe/100 g for 15 fruits; >50 mg/100 g for 11 type-A
      vegetables; <50 mg/100 g for 8 type-B vegetables; <=50 mg/100 g for 7 type-C
      vegetables. The percentage of Phe in protein varied from 3.13 +/- 1.03% to 3.74
      +/- 2.55% in fruits; 3.33 +/- 1.41 to 4.82 +/- 1.17 in type-A vegetables; 3.46 +/
      1.25% to 4.83 +/- 2.46 in type-B vegetables; and 3.14% +/- 1.49 to 4.62% +/-
      2.26 in type-C vegetables. CONCLUSIONS: The Phe and protein contents provided by
      most FCTs were positively correlated, suggesting that it is possible to estimate
      the Phe content of fruits by multiplying its protein content by 3%. For type-A, 
      B, and -C vegetables, 4% may be used.

PMID- 27718211
TI  - Review of functional MRI in HIV: effects of aging and medication.
AB  - HIV-associated neurocognitive disorder (HAND) is a frequently occurring
      comorbidity of HIV infection. Evidence suggests this condition starts subclinical
      before a progression to a symptomatic stage. Blood oxygenated level dependent
      (BOLD) fMRI has shown to be a sensitive tool to detect abnormal brain function in
      an early stage and might therefore be useful to evaluate the effect of HIV
      infection on brain function. An extensive literature search was performed in June
      2015. Eligibility criteria for included studies were as follows: (1) conducting
      with HIV-positive patients, (2) using BOLD fMRI, and (3) including a HIV-negative
      control group. A total of 19 studies were included in the review including 931
      participants. Differences in activation between HIV-positive and -negative
      participants were found when testing multiple domains, i.e., attention, (working)
      memory, and especially executive functioning. Overall, HIV-positive patients
      showed hyperactivation in task-related brain regions despite equal performances
      as controls. Task performance was degraded only for the most complex tasks. A few
      studies investigated the effect of aging on fMRI, and most of them found no
      interaction with HIV infection. Only three studies evaluated the effect of
      combination antiretroviral therapy (cART) on functional data suggesting an
      increase in activation with the use of cART. fMRI is a sensitive instrument to
      detect subtle cognitive changes in HIV patients. Open questions remain regarding
      the effects of cART on fMRI and the effects of aging on fMRI.

PMID- 27718213
TI  - Whole resting cells vs. cell free extracts of Candida parapsilosis ATCC 7330 for
      the synthesis of gold nanoparticles.
AB  - The cell free extracts of Candida parapsilosis ATCC 7330 are more efficient than
      the whole resting cells of the yeast in the synthesis of directly usable gold
      nanoparticles as revealed by this systematic study. Cell free extracts yielded
      gold nanoparticles of hydrodynamic diameter (50-200 nm). In this study, the total
      protein concentration influences the nanofabrication and not only the reductase
      enzymes as originally thought. Powder X-ray diffraction studies confirm the
      crystalline nature of the gold nanoparticles. Fourier Transform Infra Red
      spectroscopy and thermal gravimetric analysis suggests that the biosynthesized
      gold nanoparticles are capped by peptides/proteins. Dispersion experiments
      indicate a stable dispersion of gold nanoparticles in pH 12 solutions which is
      also confirmed by electron microscopic analysis and validated using a surface
      plasmon resonance assay. The effectiveness of the dispersed nanoparticles for the
      reduction of 4-nitrophenol using sodium borohydride as a reductant further
      confirms the formation of functional gold nanoparticles. It is also reported that
      gold nanoparticles with mean particle diameter of 27 nm are biosynthesized inside
      the whole cell by transmission electron microscopy analysis. With optimized
      reaction conditions, maximum gold bioaccumulation with the 24 h culture age of
      the yeast with cellular uptake of ~1010 gold atoms at the single cell level is
      achieved but it is not easy to extract the gold nanoparticles from the whole
      resting cells.

PMID- 27718214
TI  - Effect of textile dyes on activity and differential regulation of laccase genes
      from Pleurotus ostreatus grown in submerged fermentation.
AB  - This research was conducted to extend the knowledge on the differential
      regulation of laccase genes in response to dyes. In order to accomplish this, we
      analyzed both, the expression of five laccase genes by real time RT-qPCR, and
      also the laccase activity and isoforms patterns during the time-course of a
      Pleurotus ostreatus submerged fermentation supplemented with either acetyl yellow
      G (AYG) or remazol brilliant blue R (RBBR) dyes. For the purpose of obtaining a
      stable reference gene for optimal normalization of RT-quantitative PCR gene
      expression assays, we tested four candidate reference genes. As a result of this
      analysis, gpd was selected as reference index for data normalization. The
      addition of dyes had an induction effect on the enzymatic activity and also
      modified the zymogram profile. Fermentation with RBBR showed the highest laccase
      activity and number of isoforms along the course of the fermentation. Laccase
      gene expression profiles displayed up/down regulation along the fermentation time
      in four laccase genes (pox4, pox3, poxa1b and pox2), while pox1 was not expressed
      in either of the fermentation conditions. AYG addition caused the highest
      induction and repression levels for genes pox3 and poxa1b respectively. The
      expression level for all genes in the presence of RBBR were lower than in AYG,
      being in both conditions this response growth time dependent. These results show
      the influence of the nature of dyes on the induction level of laccase activity
      and on the differential regulation of the laccase genes expression in P.
      ostreatus.

PMID- 27718215
TI  - Pyruvate production using engineered Escherichia coli.
AB  - Pyruvate plays an essential role in the central carbon metabolism of multiple
      organisms and is used as a raw material in the chemical, biochemical and
      pharmaceutical industries. To meet demand, large amounts of pyruvate are produced
      through fermentation processes. Here we describe a simple and efficient method
      for producing pyruvate in Escherichia coli. To stop carbon flux from pyruvate to
      fatty acids, the accBC genes, which encode the enzyme that catalyzes the first
      step of fatty acid biosynthesis and is essential for vegetative growth, were
      manipulated within the genome; its native promoter was replaced with the
      tetracycline (or doxycycline)-regulated promoter and the corresponding
      transcriptional regulator genes. The resulting strain grew normally in the
      presence of doxycycline, but showed poor growth upon withdrawal of doxycycline.
      Using this strain, we developed a high pyruvate producing strain (strain LAFCPCPt
      accBC-aceE), in which the tetracycline-regulated promoter was also introduced
      upstream of aceE, and the ackA-pta, adhE, cra, ldhA, pflB and poxB genes were
      deleted. After determining the optimal culture conditions for this strain, the
      final pyruvate concentration reached 26.1 g L-1 after 72 h with a theoretical
      yield of 55.6 %. These levels are high enough to indicate that the developed
      strain has the potential for application to industrial production of pyruvate.

PMID- 27718216
TI  - Predictors of Progression in IgA Nephropathy in Childhood.
AB  - The aim of this retrospective study was to assess the usefulness of potential
      predictors of poor prognosis in IgA nephropathy in children. The study population
      consisted of 55 children aged 11 +/- 4 years, diagnosed on the basis of the
      Oxford classification and MEST score of kidney biopsy findings. Proteinuria,
      glomerular filtration rate (GFR), and the IgA/C3 serum ratio were assessed in all
      patients twice: at onset and at follow-up. The patients were treated with
      steroids, immunosuppressive drugs, and/or angiotensin-converting enzyme
      inhibitors. Follow-up was at 3.9 +/- 2.9 (median 2.7) years. The patients were
      subdivided into two groups: with GFR <90 and >=90 mL/min at follow-up. ROC AUC
      curves and logistic regression were used to evaluate the power of prognostic
      factors. The two groups did not differ regarding the level of proteinuria, MEST
      score, and the IgA/C3 ratio at onset of disease. There was a significant
      association between GFR reductions at onset and follow-up (AUC = 0.660; p <
      0.05). In patients with nephrotic range proteinuria at onset, proteinuria at
      follow-up was more frequent compared with other patients (AUC = 0.760; p < 0.05),
      MEST score >=3 tended to be associated with reduced GFR (AUC = 0.650; p = 0.07)
      but not with proteinuria (AUC = 0.608; p = 0.47), and the IgA/C3 ratio was higher
      (p < 0.05) at follow-up. No significant associations were found between the
      IgA/C3 ratio at onset and reduced GFR (AUC = 0.565; p = 0.46) or proteinuria at
      follow-up (AUC = 0.263; p = 0.20). We conclude that predictors of poor outcome in
      childhood IgAN include the following: GFR reduction, nephrotic range proteinuria
      at onset of disease, and high MEST score in Oxford classification of kidney
      biopsy. Despite a higher serum IgA/C3 ratio in children with impaired renal
      function in long-term follow-up, we failed to demonstrate a significant
      association between this ratio at onset of disease and reduced GFR or persistent
      proteinuria at follow-up. Thus, IgA/C3 ratio is not a good foreteller of
      progression of IgA nephropathy in childhood.

PMID- 27718217
TI  - Animal Models of Implant-Related Low-Grade Infections. A Twenty-Year Review.
AB  - The demand for joint replacement and surgical treatment is continuously
      increasing, thus representing a clinical burden and a cost for the healthcare
      system. Among several pathogens involved in implant-related infections,
      staphylococci account for the two-thirds of clinically isolated bacteria. Despite
      most of them are highly virulent microorganisms (Staphylococcus aureus,
      Escherichia coli, Pseudomonas aeruginosa), low virulent bacteria (Staphylococcus
      epidermidis, Propionibacterium acnes) are responsible for delayed, low-grade
      infections without specific clinical signs and hardly distinguishable from
      aseptic prosthetic failure. Therefore, there is a real need to study the
      pathogenesis of orthopedic infections through in vivo animal models. The present
      review of the literature provides a 20-year overview of animal models of acute,
      subclinical or chronic orthopedic infections according to the pathogen virulence
      and inocula. Through this analysis, a great variety of conditions in terms of
      bacterial strains and inocula emerged, thus encouraging the development of more
      reproducible in vivo studies to provide relevant information for a translational
      approach to humans.

PMID- 27718218
TI  - Medication Adherence Contributes to an Improved Quality of Life in Type 2
      Diabetes Mellitus Patients: A Cross-Sectional Study.
AB  - INTRODUCTION: Diabetes mellitus is a chronic disease with a high prevalence world
      wide. This disease has also been reported to affect the quality of life (QOL) of
      the patient and their family due to its chronic nature and multi organ
      involvement. The aim of this study was to analyze the association between
      adherence to prescribed diabetes medication and diabetes-specific QOL in patients
      attending Secondary Health Care Facility in Bandung City, Indonesia. METHODS: A
      cross-sectional survey was conducted in the Secondary Health Care Facility in
      Bandung City, Indonesia. Data were collected between February and April 2014
      using consecutive sampling. Adherence was assessed using the eight-item Morisky
      Medication Adherence Scale while diabetes-specific-QOL was assessed using the
      Diabetes 39 instrument. RESULTS: The results showed that among the patients,
      49.4% exhibited low adherence, 29.7% exhibited medium adherence, and 20.9%
      exhibited high adherence to diabetes medication. Diabetes-specific QOL proved to
      be highly affected in the sexual functioning domain. Social-burden domain scores
      were better than overall QOL scores. There was a significant association between
      adherence and diabetes-specific QOL (p = 0.009) using The Kruskall-Wallis test of
      significance. The results of the post hoc Mann-Whitney tests (high vs medium
      adherence, p = 0.084; medium vs low adherence, p = 0.86; and high vs low
      adherence, p = 0.001) indicated that higher adherence to prescribed diabetes
      medication contributed to an improved QOL. Multiple regression analysis showed
      that the predictors of diabetes-specific QOL were adherence and patient income.
      CONCLUSIONS: Adherence to prescribed medication showed a positive effect on
      diabetes-specific QOL in patients. Patients with a high adherence to medication
      had an improved QOL. This result is important not only in developing intervention
      programs for patients but also in improving their QOL through sustainable health
      promotion.

PMID- 27718219
TI  - Molecular heterogeneity of aggrecan-based perineuronal nets around five
      subclasses of parvalbumin-expressing neurons in the mouse hippocampus.
AB  - Subsets of GABAergic neurons are surrounded by perineuronal nets (PNNs), which
      play a critical role in the regulation of neural plasticity and neuroprotection.
      Although the plant lectin Wisteria floribunda agglutinin (WFA) has been commonly
      used to label PNNs, WFA only detects N-acetyl-d-galactosamine on aggrecan, a
      member of the lectican family. In this study, we used WFA and the antibody
      against the core protein of aggrecan (ACAN) to investigate the molecular
      heterogeneity of aggrecan-based PNNs around five subclasses of parvalbumin
      expressing (PV+) gamma-aminobutyric acid (GABA)ergic neurons in the CA1 and CA3
      regions of the mouse hippocampus. The vast majority of ACAN+ PNNs were
      colocalized with WFA in the stratum pyramidale, whereas a substantial population
      of ACAN+ PNNs lacked WFA labeling in the stratum oriens. We then defined the
      subclasses of PV+ neurons based on their cellular locations, molecular
      expression, and septal projection. Like the WFA+ PNNs, ACAN+ PNNs surrounded PV+
      basket cells and bistratified cells but not axo-axonic cells. Unlike the WFA+
      PNNs, ACAN+ PNNs frequently surrounded PV+ oriens-lacunosum moleculare cells and
      hippocampo-septal cells. Interestingly, the relative densities of GABAergic
      synapses were higher around PV+ neurons with ACAN+ PNNs than around those without
      ACAN+ PNNs. Degradation of WFA+ PNNs by chondroitinase ABC did not affect the
      GABAergic synaptic densities around PV+ neurons. Our findings suggest that the
      molecular composition of aggrecan-based PNNs around PV+ neurons may differ in a
      subclass-specific manner, and also might help determine the functional
      involvement of PNNs in the regulation of GABAergic synapses around PV+ neurons in
      the hippocampus. J. Comp. Neurol. 525:1234-1249, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27718220
TI  - Discrimination, Internalized Homonegativity, and Attitudes Toward Children of
      Same-Sex Parents: Can Secure Attachment Buffer Against Stigma Internalization?
AB  - With increasing numbers of same-sex couples raising children in the United
      States, discriminatory attitudes toward children of same-sex parents (ACSSP) are
      of increasing concern. As with other forms of stigma and discrimination, lesbian,
      gay, and bisexual (LGB) individuals are at risk for internalizing these societal
      attitudes, which can negatively affect parenting-related decisions and behaviors
      and the mental and physical health of their children. Secure attachment is
      characterized by positive views of the self as loveable and worthy of care that
      are understood to develop in early relationships with caregivers. Secure
      attachment has been associated with positive mental and physical health,
      including among LGB individuals and couples. This study aimed to test the
      potential buffering role of secure attachment against stigma internalization by
      examining associations among secure attachment, discrimination, internalized
      homonegativity (IH), and ACSSP in an online survey study of 209 U.S. adults in
      same-sex relationships. Bootstrap analyses supported our hypothesized moderated
      mediation model, with secure attachment being a buffer. Greater discrimination
      was indirectly associated with more negative ACSSP through greater IH for
      individuals with mean or lower levels, but not for individuals with higher than
      average levels of secure attachment, specifically because among those with higher
      levels of secure attachment, discrimination was not associated with IH. These
      findings build on and extend past research, with important implications for
      future research and clinical work with LGB individuals, same-sex couples, and
      their families, including potential implementation of interventions targeting
      attachment security.

PMID- 27718221
TI  - Auditory toxicity in late preterm and term neonates with severe jaundice.
AB  - AIM: Jaundice may cause auditory toxicity (auditory neuropathy and hearing loss).
      However, total serum bilirubin (TSB) does not discriminate neonates at risk for
      auditory toxicity. We compared TSB, bilirubin:albumin molar ratio (BAMR), and
      unbound bilirubin for their association with auditory toxicity in neonates with
      severe jaundice (TSB >=342MUmol/L, or that met exchange transfusion). METHOD:
      Neonates greater or equal to 34 weeks gestational age with severe jaundice during
      the first 2 postnatal weeks were eligible for prospective cohort study, unless
      they had craniofacial malformations, chromosomal disorders, toxoplasmosis, other
      infections, rubella, cytomegalovirus, herpes simplex infections, surgery, or
      family history of congenital deafness. RESULTS: Twenty-eight out of 100 neonates
      (mean gestational age 37.4wks; 59 males, 41 females) had auditory toxicity. Peak
      unbound bilirubin, but not peak TSB and BAMR, was associated with auditory
      toxicity (p<0.05) in neonates with severe (TSB <427.5MUmol/L) and extreme
      hyperbilirubinemia (TSB >=427.5MUmol/L). Area under the receiver operating
      characteristic curve for unbound bilirubin (0.78) was significantly greater
      (p=0.03) than TSB (0.54) among neonates with severe but not extreme
      hyperbilirubinemia. INTERPRETATION: Unbound bilirubin is more strongly associated
      with auditory toxicity than TSB and/or BAMR in greater or equal to 34 weeks
      gestational age neonates with severe jaundice. Unbound bilirubin is a better
      predictor than TSB in neonates with severe hyperbilirubinemia.

PMID- 27718222
TI  - DNA-doxorubicin interaction: New insights and peculiarities.
AB  - We have investigated the interaction of the DNA molecule with the anticancer drug
      doxorubicin (doxo) by using three different experimental techniques: single
      molecule stretching, single molecule imaging, and dynamic light scattering. Such
      techniques allowed us to get new insights on the mechanical behavior of the DNA
      doxo complexes as well as on the physical chemistry of the interaction. First,
      the contour length data obtained from single molecule stretching were used to
      extract the physicochemical parameters of the DNA-doxo interaction under
      different buffer conditions. This analysis has proven that the physical chemistry
      of such interaction can be modulated by changing the ionic strength of the
      surrounding buffer. In particular we have found that at low ionc strengths doxo
      interacts with DNA by simple intercalation (no aggregation) and/or by forming
      bound dimers. For high ionic strengths, otherwise, doxo-doxo self-association is
      enhanced, giving rise to the formation of bound doxo aggregates composed by 3 to
      4 molecules along the double-helix. On the other hand, the results obtained for
      the persistence length of the DNA-doxo complexes is strongly force-dependent,
      presenting different behaviors when measured with stretching or non-stretching
      techniques.

PMID- 27718223
TI  - Observed Mother- and Father-Child Interaction Differences in Families with
      Medically Assisted Reproduction-Conceived Twins and Singletons.
AB  - Increased medically assisted reproduction (MAR) use to treat infertility has
      resulted in a growing twin birth rate. Little is known about parent-child
      relationships for twin relative to singleton children in middle childhood. This
      study fills this gap by examining parent-child relationships in 57 families with
      eighty 6- to 12-year-old MAR twin and singleton children using observational data
      (warm and supportive communication, control, and hostility). Nested ANCOVAs
      indicate that while mothers exhibit similar interactional behaviors toward twins
      and singletons, fathers have less optimum behaviors toward twins relative to
      singletons. Twins displayed less engaged behavior with mothers and fathers
      relative to singletons. Given the vitality of parent-child relationships for
      family and child adjustment, future studies should examine determinants and
      outcomes of twin-singleton relationship differences to bolster twins' and their
      families' functioning.

PMID- 27718224
TI  - Active tuberculosis detection by pouched rats in 2014: More than 2,000 new
      patients found in two countries.
AB  - Tuberculosis (TB) is a major problem in poor countries because sensitive
      diagnostic tools are unavailable. In 2014, our pouched rats evaluated sputum from
      21,600 Tanzanians and 9,048 Mozambicans whose sputum had previously been
      evaluated by microscopy, the standard diagnostic for TB. Evaluation by the rats
      revealed 1,412 new patients with active TB in Tanzania and 645 new patients in
      Mozambique, increases of 39% and 53%, respectively, when compared to detections
      by microscopy alone. These results provide further support for the applied use of
      scent-detecting rats.

PMID- 27718225
TI  - The evolution of coexistence: Reciprocal adaptation promotes the assembly of a
      simple community.
AB  - Species coexistence may result by chance when co-occurring species do not
      strongly interact or it may be an evolutionary outcome of strongly interacting
      species adapting to each other. Although patterns like character displacement
      indicate that coexistence has often been an evolutionary outcome, it is unclear
      how often the evolution of coexistence represents adaptation in only one species
      or reciprocal adaptation among all interacting species. Here, we demonstrate a
      strong role for evolution in the coexistence of guppies and killifish in
      Trinidadian streams. We experimentally recreated the temporal stages in the
      invasion and establishment of guppies into communities that previously contained
      only killifish. We combined demographic responses of guppies and killifish with a
      size-based integral projection model to calculate the fitness of the phenotypes
      of each species in each of the stages of community assembly. We show that guppies
      from locally adapted populations that are sympatric with killifish have higher
      fitness when paired with killifish than guppies from allopatric populations. This
      elevated fitness involves effects traceable to both guppy and killifish
      evolution. We discuss the implications of our results to the study of species
      coexistence and how it may be mediated through eco-evolutionary feedbacks.

PMID- 27718226
TI  - Hepatocyte growth factor reduces CXCL10 expression in keratinocytes.
AB  - Keratinocytes secrete vascular endothelial growth factor (VEGF) and
      angioregulatory chemokines during cutaneous wound healing. Hepatocyte growth
      factor (HGF) promotes skin re-epithelialization by increasing VEGF expression in
      keratinocytes. Here, we investigated the regulatory roles of HGF in the
      expression of genes encoding angiogenic and angiostatic chemokines in
      keratinocytes and found that HGF specifically inhibits mRNA expression of the
      angiostatic chemokine CXCL10 in both mouse primary keratinocytes and in the human
      keratinocyte cell line HaCaT through the MEK/ERK cascade. Furthermore, HGF
      inhibited tumor necrosis factor-alpha-induced CXCL10 expression at both mRNA and
      protein levels in HaCaT cells. Thus, HGF may orchestrate angiogenesis in wounded
      skin by modulating both VEGF and CXCL10 expression in keratinocytes.

PMID- 27718227
TI  - A parallel stranded G-quadruplex composed of threose nucleic acid (TNA).
AB  - G-rich sequences can adopt four-stranded helical structures, called G
      quadruplexes, that self-assemble around monovalent cations like sodium (Na+ ) and
      potassium (K+ ). Whether similar structures can be formed from xeno-nucleic acid
      (XNA) polymers with a shorter backbone repeat unit is an unanswered question with
      significant implications on the fold space of functional XNA polymers. Here, we
      examine the potential for TNA (alpha-l-threofuranosyl nucleic acid) to adopt a
      four-stranded helical structure based on a planar G-quartet motif. Using native
      polyacrylamide gel electrophoresis (PAGE), circular dichroism (CD) and solution
      state nuclear magnetic resonance (NMR) spectroscopy, we show that despite a
      backbone repeat unit that is one atom shorter than the backbone repeat unit found
      in DNA and RNA, TNA can self-assemble into stable G-quadruplex structures that
      are similar in thermal stability to equivalent DNA structures. However, unlike
      DNA, TNA does not appear to discriminate between Na+ and K+ ions, as G-quadruplex
      structures form equally well in the presence of either ion. Together, these
      findings demonstrate that despite a shorter backbone repeat unit, TNA is capable
      of self-assembling into stable G-quadruplex structures.

PMID- 27718228
TI  - Prediction of renal function upon reperfusion by ex situ controlled oxygenated
      rewarming.
AB  - BACKGROUND: Post-transplant function of suboptimal kidney grafts can be improved
      but not accurately predicted by hypothermic machine perfusion. Therefore, a new
      concept of ex situ pre-implantation machine perfusion with controlled rewarming
      up to subnormothermic temperatures was developed and evaluated. MATERIALS AND
      METHODS: Porcine kidneys (n = 6/group) were retrieved before or 30 min after
      cardiac arrest of the donor and subjected to 18 h of static cold storage. In some
      cases, 90 min of machine-controlled oxygenated rewarming (COR) was added
      thereafter. Functional integrity was evaluated in all kidneys by subsequent
      normothermic reperfusion in vitro. After supplementation of the preservation
      solution (Custodiol-N solution + 5 g/L dextran 40) with 10 mg/dL creatinine, ex
      situ renal function was assessed by monitoring urine output, urinary creatinine
      and creatinine clearance at 20  degrees C. Functional integrity was evaluated in
      all kidneys by normothermic reperfusion. RESULTS: COR resulted in a more than
      twofold improvement of postreperfusion creatinine clearance, oxygen consumption
      and enzyme release upon reperfusion, when compared with static cold storage.
      Predictive discrimination between kidneys with good or impaired function upon
      reperfusion based on parameters during perfusion at 4  degrees C was only
      moderate. This improved significantly at 20  degrees C. Correlation with renal
      clearance upon reperfusion was weak for vascular resistance at 8 degrees  (r2 =
      0.2) and 20  degrees C (r2 = 0.41). Best correlation was found for clearance
      measurements at 20 degrees  (r2 = 0.81). CONCLUSIONS: Reconditioning by
      controlled oxygenated rewarming up to 20  degrees C improves renal function after
      reperfusion and can be utilized to assess graft integrity of predamaged donor
      kidneys.

PMID- 27718229
TI  - Nicotinic acetylcholine receptors regulate vestibular afferent gain and
      activation timing.
AB  - Little is known about the function of the cholinergic efferents innervating
      peripheral vestibular hair cells. We measured vestibular sensory evoked
      potentials (VsEPs) in alpha9 knockout (KO) mice, alpha10 KO mice, alpha7 KO mice,
      alpha9/10 and alpha7/9 double KO mice, and wild-type (WT) controls. We also
      studied the morphology and ultrastructure of efferent terminals on vestibular
      hair cells in alpha9, alpha10, and alpha9/10 KOs. Both type I and type ll
      vestibular hair cells express the alpha9 and alpha10 subunits. The efferent
      boutons on vestibular cells in alpha9, alpha10, and alpha9/10 KOs appeared
      normal, but a quantitative analysis was not performed. Mean VsEP thresholds were
      significantly elevated in alpha9 and alpha9/10 KO animals. Some alpha9 and
      alpha9/10 KO animals, however, had normal or near-normal thresholds, whereas
      others were greatly affected. Despite individual variability in threshold
      responses, latencies were consistently shortened. The double alpha7/9 KO resulted
      in decreased variance by normalizing waveforms and latencies. The phenotypes of
      the alpha7 and alpha10 single KOs were identical. Both alpha7 and alpha10 KO mice
      evidenced normal thresholds, decreased activation latencies, and larger
      amplitudes compared with WT mice. The data suggest a complex interaction of
      nicotinic acetylcholine receptors (nAChRs) in regulating vestibular afferent gain
      and activation timing. Although the alpha9/10 heteromeric nAChR is an important
      component of vestibular efferent activity, other peripheral or central nAChRs
      involving the alpha7 subunit or alpha10 subunit and alpha9 homomeric receptors
      are also important. J. Comp. Neurol. 525:1216-1233, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27718230
TI  - Computer vision-based method for classification of wheat grains using artificial
      neural network.
AB  - BACKGROUND: A simplified computer vision-based application using artificial
      neural network (ANN) depending on multilayer perceptron (MLP) for accurately
      classifying wheat grains into bread or durum is presented. The images of 100
      bread and 100 durum wheat grains are taken via a high-resolution camera and
      subjected to pre-processing. The main visual features of four dimensions, three
      colors and five textures are acquired using image-processing techniques (IPTs). A
      total of 21 visual features are reproduced from the 12 main features to diversify
      the input population for training and testing the ANN model. The data sets of
      visual features are considered as input parameters of the ANN model. The ANN with
      four different input data subsets is modelled to classify the wheat grains into
      bread or durum. The ANN model is trained with 180 grains and its accuracy tested
      with 20 grains from a total of 200 wheat grains. RESULTS: Seven input parameters
      that are most effective on the classifying results are determined using the
      correlation-based CfsSubsetEval algorithm to simplify the ANN model. The results
      of the ANN model are compared in terms of accuracy rate. The best result is
      achieved with a mean absolute error (MAE) of 9.8 * 10-6 by the simplified ANN
      model. CONCLUSION: This shows that the proposed classifier based on computer
      vision can be successfully exploited to automatically classify a variety of
      grains. (c) 2016 Society of Chemical Industry.

PMID- 27718234
TI  - Drug Transporters: Advances and Opportunities.
AB  - Drug transporter research conducted over the last several decades has led to a
      greatly advanced understanding of the mechanisms underlying the principles of
      drug absorption and disposition. Although many transporters remain poorly
      characterized, there is ample evidence that the drug transporter field will
      ultimately provide vital support to routine patient management, and will play a
      key role in the discovery, development, and evaluation of innovative, cutting
      edge therapies.

PMID- 27718235
TI  - The soluble cytoplasmic tail of CD45 (ct-CD45) in human plasma contributes to
      keep T cells in a quiescent state.
AB  - The cytoplasmic tail of CD45 (ct-CD45) is proteolytically cleaved and released
      upon activation of human phagocytes. It acts on T cells as an inhibitory,
      cytokine-like factor in vitro. Here, we show that ct-CD45 is abundant in human
      peripheral blood plasma from healthy adults compared with plasma derived from
      umbilical cord blood and plasma from patients with rheumatoid arthritis or
      systemic lupus erythematosus. Plasma depleted of ct-CD45 enhanced T-cell
      proliferation, while addition of exogenous ct-CD45 protein inhibited
      proliferation and reduced cytokine production of human T lymphocytes in response
      to TCR signaling. Inhibition of T-cell proliferation by ct-CD45 was overcome by
      costimulation via CD28. T-cell activation in the presence of ct-CD45 was
      associated with an upregulation of the quiescence factors Schlafen family member
      12 (SLFN12) and Krueppel-like factor 2 (KLF2) as well as of the cyclin-dependent
      kinase (CDK) inhibitor p27kip1. In contrast, positive regulators of the cell
      cycle such as cyclin D2 and D3 as well as CDK2 and CDK4 were found to be
      downregulated in response to ct-CD45. In summary, we demonstrate that ct-CD45 is
      present in human plasma and sets the threshold of T-cell activation.

PMID- 27718236
TI  - Production of chlorothalonil hydrolytic dehalogenase from agro-industrial
      wastewater and its application in raw food cleaning.
AB  - BACKGROUND: To reduce the fermentation cost for industrialization of
      chlorothalonil hydrolytic dehalogenase (Chd), agro-industrial wastewaters
      including molasses, corn steep liquor (CSL) and fermentation wastewater were used
      to substitute for expensive carbon and nitrogen sources and fresh water for lab
      preparation. RESULTS: The results showed that molasses and CSL could replace 5%
      carbon source and 100% organic nitrogen source respectively to maintain the same
      fermentation level. Re-fermentation from raffinate of ultra-filtered fermentation
      wastewater could achieve 61.03% of initial Chd activity and reach 96.39% activity
      when cultured in a mixture of raffinate and 50% of original medium constituent.
      Typical raw foods were chosen to evaluate the chlorothalonil removal ability of
      Chd. After Chd treatment for 2 h at room temperature, 97.40 and 75.55% of 30 mg
      kg-1 chlorothalonil on cherry tomato and strawberry respectively and 60.29% of 50
      mg kg-1 chlorothalonil on Chinese cabbage were removed. Furthermore, the residual
      activity of the enzyme remained at 78-82% after treatment, suggesting its
      potential for reuse. CONCLUSION: This study proved the cost-feasibility of large
      scale production of Chd from agro-industrial wastewater and demonstrated the
      potential of Chd in raw food cleaning. (c) 2016 Society of Chemical Industry.

PMID- 27718237
TI  - Adaptive, but not condition-dependent, body shape differences contribute to
      assortative mating preferences during ecological speciation.
AB  - Assortative mating is critical for reproductive isolation during speciation;
      however, the mechanisms underlying mating preferences are often unknown.
      Assortative mating can be mediated through preferences for condition-dependent
      and adaptive ("magic") traits, but rigorously testing these hypotheses has been
      impeded by trait covariation in living organisms. We used computer-generated
      models to examine the role of body shape in producing association preferences
      between fish populations undergoing ecological speciation in different habitat
      types. We demonstrate that body shape can serve as an adaptive trait (variation
      in head size between populations) and a condition-dependent signal (variation in
      abdominal distention among individuals). Female preferences for stimuli varying
      in only one aspect of body shape uncovered evidence for body shape as a magic
      trait across population pairs, but no evidence for body shape serving as a
      condition-dependent signal. Evolution of preferences only in females from one
      habitat type as well as stronger preferences in sympatric nonsulfidic as opposed
      to allopatric nonsulfidic populations suggests that reinforcement may have played
      a role in producing the observed patterns.

PMID- 27718238
TI  - Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.
AB  - BACKGROUND: Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated
      fatty acids give rise to electrophilic nitro-fatty acids (NO2 -FAs), such as
      nitro oleic acid (OA-NO2 ) and nitro linoleic acid (LNO2 ). Endogenous
      electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by
      modulating metabolic and inflammatory signal transduction reactions. Hence, there
      is considerable interest in employing NO2 -FAs and other EFAs for the prevention
      and treatment of inflammatory disorders. Thus, we sought to determine whether OA
      NO2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous
      inflammation. METHODS: We evaluated the effect of OA-NO2 on allergic contact
      dermatitis (ACD) using an established model of contact hypersensitivity in
      C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. RESULTS: We found
      that subcutaneous (SC) OA-NO2 injections administered 18 h prior to sensitization
      and elicitation suppresses ACD in both preventative and therapeutic models. In
      vivo SC OA-NO2 significantly inhibits pathways that lead to inflammatory cell
      infiltration and the production of inflammatory cytokines in the skin. Moreover,
      OA-NO2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO2 treatment
      results in anti-inflammatory effects capable of inhibiting ACD by inducing
      immunosuppressive responses. CONCLUSION: Overall, these results support the
      development of OA-NO2 as a promising therapeutic for ACD and provides new
      insights into the role of electrophilic fatty acids in the control of cutaneous
      immune responses potentially relevant to a broad range of allergic and
      inflammatory skin diseases.

PMID- 27718239
TI  - Long-term manure amendments and chemical fertilizers enhanced soil organic carbon
      sequestration in a wheat (Triticum aestivum L.)-maize (Zea mays L.) rotation
      system.
AB  - BACKGROUND: The carbon sequestration potential is affected by cropping system and
      management practices, but soil organic carbon (SOC) sequestration potential under
      fertilizations remains unclear in north China. This study examined SOC change,
      total C input to soil and, via integration of these estimates over years, carbon
      sequestration efficiency (CSE, the ratio of SOC change over C input) under no
      fertilization (control), chemical nitrogen fertilizer alone (N) or combined with
      phosphorus and potassium fertilizers (NP, NK, PK and NPK), or chemical
      fertilizers combined with low or high (1.5*) manure input (NPKM and 1.5NPKM).
      RESULTS: Results showed that, as compared with the initial condition, SOC content
      increased by 0.03, 0.06, 0.05, 0.09, 0.16, 0.26, 0.47 and 0.68 Mg C ha-1 year-1
      under control, N, NK, PK, NP, NPK, NPKM and 1.5NPKM treatments respectively.
      Correspondingly, the C inputs of wheat and maize were 1.24, 1.34, 1.55, 1.33,
      2.72, 2.96, 2.97 and 3.15 Mg ha-1 year-1 respectively. The long-term
      fertilization-induced CSE showed that about 11% of the gross C input was
      transformed into SOC pool. CONCLUSION: Overall, this study demonstrated that
      decade-long manure input combined with chemical fertilizers can maintain high
      crop yield and lead to SOC sequestration in north China. (c) 2016 Society of
      Chemical Industry.

PMID- 27718240
TI  - Neurological Disorders Depression Inventory-Epilepsy for Youth: Developed for
      epilepsy, but is it epilepsy-specific?

PMID- 27718241
TI  - In response: Neurological Disorders Depression Inventory-Epilepsy for Youth.

PMID- 27718242
TI  - Comment on falling status epilepticus mortality rates in England and Wales: 2001
      2013.

PMID- 27718243
TI  - Visible and invisible seizure symptoms.

PMID- 27718244
TI  - In response: Comment on falling status epilepticus mortality rates in England and
      Wales: 2001-2013.

PMID- 27718245
TI  - Real-world effectiveness of antipsychotics.

PMID- 27718246
TI  - NMR study of the antifreeze activities of active and inactive isoforms of a type
      III antifreeze protein.
AB  - The quaternary-amino-ethyl 1 (QAE1) isoforms of type III antifreeze proteins
      (AFPs) prevent the growth of ice crystals within organisms living in polar
      regions. We determined the antifreeze activity of wild-type and mutant constructs
      of the Japanese notched-fin eelpout (Zoarces elongates Kner) AFP8 (nfeAFP8) and
      characterized the structural and dynamics properties of their ice-binding surface
      using NMR. We found that the three constructs containing the V20G mutation were
      incapable of stopping the growth of ice crystals and exhibited structural
      changes, as well as increased conformational flexibility, in the first 310 helix
      (residues 18-22) of the sequence. Our results suggest that the inactive nfeAFP8s
      are incapable of anchoring water molecules due to the unusual and flexible
      backbone conformation of their primary prism plane-binding surface.

PMID- 27718247
TI  - TIM29 is a subunit of the human carrier translocase required for protein
      transport.
AB  - Hydrophobic inner mitochondrial membrane proteins with internal targeting
      signals, such as the metabolite carriers, use the carrier translocase (TIM22
      complex) for transport into the inner membrane. Defects in this transport pathway
      have been associated with neurodegenerative disorders. While the TIM22 complex is
      well studied in baker's yeast, very little is known about the mammalian TIM22
      complex. Using immunoprecipitation, we purified the human carrier translocase and
      identified a mitochondrial inner membrane protein TIM29 as a novel component,
      specific to metazoa. We show that TIM29 is a constituent of the 440 kDa TIM22
      complex and interacts with oxidized TIM22. Our analyses demonstrate that TIM29 is
      required for the structural integrity of the TIM22 complex and for import of
      substrate proteins by the carrier translocase.

PMID- 27718248
TI  - A cluster-randomised, controlled trial of the impact of Cogmed Working Memory
      Training on both academic performance and regulation of social, emotional and
      behavioural challenges.
AB  - BACKGROUND: We explored whether school-based Cogmed Working Memory Training
      (CWMT) may optimise both academic and psychological outcomes at school. Training
      of executive control skills may form a novel approach to enhancing processes that
      predict academic achievement, such as task-related attention, and thereby
      academic performance, but also has the potential to improve the regulation of
      emotion, social problems and behavioural difficulties. METHODS: Primary school
      children (Mean age = 12 years, N = 148) were cluster-randomised to complete
      active CWMT, a nonadaptive/placebo version of CWMT, or no training. RESULTS: No
      evidence was found for training effects on task-related attention when performing
      academic tasks, or performance on reading comprehension and mathematics tasks, or
      teacher-reported social, emotional and behavioural difficulties. CONCLUSIONS:
      CWMT did not improve control of attention in the classroom, or regulation of
      social, emotional and behavioural difficulties.

PMID- 27718249
TI  - Glutathione upregulates cAMP signalling via G protein alpha 2 during the
      development of Dictyostelium discoideum.
AB  - Despite the importance of glutathione in Dictyostelium, the role of glutathione
      synthetase (gshB/GSS) has not been clearly investigated. In this study, we
      observed that increasing glutathione content by constitutive expression of gshB
      leads to mound-arrest and defects in 3',5'-cyclic adenosine monophosphate (cAMP)
      mediated aggregation and developmental gene expression. The overexpression of
      gpaB encoding G protein alpha 2 (Galpha2), an essential component of the cAMP
      signalling pathway, results in a phenotype similar to that caused by gshB
      overexpression, whereas gpaB knockdown in gshB-overexpressing cells partially
      rescues the above-mentioned phenotypic defects. Furthermore, Galpha2 is highly
      enriched at the plasma membrane of gshB-overexpressing cells compared to wild
      type cells. Therefore, our findings suggest that glutathione upregulates cAMP
      signalling via Galpha2 modulation during Dictyostelium development.

PMID- 27718250
TI  - European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI):
      a real-life clinical assessment.
AB  - BACKGROUND: Outside clinical trials, data on systemic reactions (SRs) due to
      allergen immunotherapy (AIT) are scarce. METHODS: A prospective, longitudinal,
      web-based survey of 'real-life' respiratory allergen immunotherapy (AIT) clinical
      practice was conducted in France, Germany and Spain. SRs were recorded and coded
      according to the Medical Dictionary for Regulatory Activities (MedDRA) and risk
      factors associated with SRs were identified. RESULTS: A total of 4316 patients
      (corresponding to 4363 ongoing courses of AIT) were included. A total of 109 SRs
      were recorded, and 90 patients (2.1%) presented at least one SR. Most of the SRs
      occurred in subcutaneous allergen immunotherapy (SCIT) (89%, n = 97). The most
      frequently reported symptoms were urticaria, rhinitis, dyspnoea and cough.
      Respiratory symptoms appeared before skin symptoms. Most SRs occurred during the
      up-dosing phase (75.8%) and were mild in severity (71.6%). Intramuscular
      adrenaline was administered in 17 SRs, but only 65% of these were subsequently
      classified as anaphylaxis. Independent risk factors for SRs during SCIT were as
      follows: the use of natural extracts (odds ratio, OR) [95% confidence interval
      (CI)] = 2.74 [1.61-4.87], P = 0.001), the absence of symptomatic allergy
      medications (1.707 [1.008-2.892], P = 0.047), asthma diagnosis (1.74 [1.05-2.88],
      P = 0.03), sensitization to animal dander (1.93 [1.21-3.09], P = 0.006) or pollen
      (1.16 [1.03-1.30], P = 0.012) and cluster regimens (vs rush) (4.18 [1.21-14.37],
      P = 0.023). A previous episode of anaphylaxis increased the risk for anaphylaxis
      in SCIT (OR [95% CI] = 17.35 [1.91-157.28], P = 0.01). CONCLUSION: AIT for
      respiratory allergy is safe, with a low number of SRs observed in real-life
      clinical practice. A personalized analysis of risk factors could be used to
      minimize SRs.

PMID- 27718251
TI  - Speciation is associated with changing ornamentation rather than stronger sexual
      selection.
AB  - Although sexual ornamentation mediates reproductive isolation, comparative
      evidence does not support the hypothesis that stronger sexual selection promotes
      speciation. Prior analyses have neglected the possibility that decreases in
      ornamentation may also promote speciation, such that both increases and decreases
      in the strength of sexual selection and associated changes in ornamentation
      promote speciation. To test this hypothesis, we studied color ornamentation in
      one of the largest and fastest avian radiations, the estrildid finches. We show
      that more ornamented lineages do not speciate more, even though they tend to have
      faster rates of ornamental evolution, whereas changes in ornamentation (i.e.,
      increases or decreases) are associated with speciation. This indicates that
      divergence in sexually selected ornamentation, rather than stronger sexual
      selection, promotes or is otherwise associated with speciation. We also show that
      gregariousness and investment in reproduction are related to the elaboration of
      some ornamental traits, suggesting ecological influences on speciation mediated
      by ornamentation. We conclude that past work focusing specifically on the
      strength of sexual selection may have greatly underestimated the importance of
      sexual ornamentation for speciation.

PMID- 27718253
TI  - Probing gas adsorption in MOFs using an efficient ab initio widom insertion Monte
      Carlo method.
AB  - We propose a novel biased Widom insertion method that can efficiently compute the
      Henry coefficient, KH , of gas molecules inside porous materials exhibiting
      strong adsorption sites by employing purely DFT calculations. This is achieved by
      partitioning the simulation volume into strongly and weakly adsorbing regions and
      selectively biasing the Widom insertion moves into the former region. We show
      that only few thousands of single point energy calculations are necessary to
      achieve accurate statistics compared to many hundreds of thousands or millions of
      such calculations in conventional random insertions. The methodology is used to
      compute the Henry coefficient for CO2 , N2 , CH4 , and C2 H2 in M-MOF-74(M = Zn
      and Mg), yielding good agreement with published experimental data. Our results
      demonstrate that the DFT binding energy and the heat of adsorption are not
      accurate enough indicators to rank the guest adsorption properties at the Henry
      regime. (c) 2016 Wiley Periodicals, Inc.

PMID- 27718252
TI  - Efficacy of bisphosphonate as an adjunct to nonsurgical periodontal therapy in
      the management of periodontal disease: a systematic review.
AB  - AIMS: The aim of this systematic review was to assess the efficacy of
      bisphosphonate therapy as an adjunct to scaling and root planing (SRP) in the
      management of periodontitis. METHODS: Databases (MEDLINE, EMBASE, Cochrane
      Central Register of Controlled Trials and Cochrane Oral Health Group Trials
      Register databases) were searched up to and including July 2016. The primary
      outcome was probing depth (PD), and the secondary outcomes were changes in
      clinical attachment level (CAL) and bone defect (BD) fill. The mean differences
      (MD) of outcomes and 95% confidence intervals (CI) for each variable were
      calculated using random effect model. RESULTS: Eight clinical studies were
      included. Seven studies used alendronate as an adjunct to SRP; of these, four
      studies used topical application and three used oral alendronate. Considering the
      effects of adjunctive bisphosphonates as compared to SRP alone, a high degree of
      heterogeneity for PD (Q value = 39.6, P < 0.0001, I2  = 87.38%), CAL (Q value =
      13.65, P = 0.008, I2  = 70.71%), and BD fill (Q value = 53.26, P < 0.0001, I2  =
      92.49%) was noticed among both the groups. Meta-analysis showed a statistically
      significant PD reduction (MD = -1.18, 95% CI = -1.91 to -0.44, P = 0.002), CAL
      gain (MD = -0.69, 95% CI = -1.20 to -0.18, P = 0.008) and BD fill (MD = -2.36,
      95% CI = -3.64 to -1.08, P < 0.001) for SRP + bisphosphonate treatment vs. SRP
      alone. CONCLUSIONS: Adjunctive bisphosphonate therapy appears to be effective in
      managing periodontitis, however, due to the potential risk of osteonecrosis of
      the jaws and short-term follow-up of the studies, their clinical application is
      debatable.

PMID- 27718254
TI  - Immune Response of Healthy Adults to the Ingested Probiotic Lactobacillus casei
      Shirota.
AB  - Daily ingestion of a probiotic drink containing Lactobacillus casei Shirota (LcS;
      1.3 * 1010 live cells) by healthy adults for (1) 4-week LcS, (2) 6-week
      discontinuation of LcS and (3) a final 4 weeks of LcS was investigated. There was
      a significant increase in expression of the T cell activation marker CD3+ CD69+
      in ex vivo unstimulated blood cells at weeks 10 and 14, and there was a
      significant increase in the NK cell marker CD3+ CD16/56+ in ex vivo unstimulated
      blood cells at weeks 4, 10 and 14. Expression of the NK cell activation marker
      CD16/56+ CD69+ in ex vivo unstimulated blood cells was 62% higher at week 10 and
      74% higher at week 14. Intracellular staining of IL-4 in ex vivo unstimulated and
      PMA-/ionomycin-stimulated CD3+ beta7+ integrin blood cells was significantly
      lower at weeks 10 and 14. Intracellular staining of IL-12 in ex vivo unstimulated
      and LPS-stimulated CD14+ blood cells was significantly lower at weeks 4, 10 and
      14. Intracellular staining of TNF-alpha in LPS-stimulated CD14+ blood cells was
      significantly lower at weeks 4, 10 and 14. Mucosal salivary IFN-gamma, IgA1 and
      IgA2 concentrations were significantly higher at week 14, but LcS did not affect
      systemic circulating influenza A-specific IgA or IgG and tetanus-specific IgG
      antibody levels. In addition to the decrease in CD3+ beta7+ integrin cell IL-4
      and a reduced CD14+ cell pro-inflammatory cytokine profile, at week 14 increased
      expression of activation markers on circulating T cells and NK cells and higher
      mucosal salivary IgA1 and IgA2 concentration indicated a secondary boosting
      effect of LcS.

PMID- 27718255
TI  - Nonalcoholic steatohepatitis and the intestinal microbiota.

PMID- 27718256
TI  - On the Usefulness of Action Tendencies Training and Brain Stimulation in the
      Modification of Alcohol Use Disorders. A Commentary on "Electrophysiological and
      Behavioral Effects of Combined Transcranial Direct Current Stimulation and
      Alcohol Approach Bias Retraining in Hazardous Drinkers" by den Uyl, Gladwin, and
      Wiers (ACER, 2016).

PMID- 27718257
TI  - CE-MS for metabolomics: Developments and applications in the period 2014-2016.
AB  - CE-MS can be considered a useful analytical technique for the global profiling of
      (highly) polar and charged metabolites in various samples. Over the past few
      years, significant advancements have been made in CE-MS approaches for
      metabolomics studies. In this paper, which is a follow-up of a previous review
      paper covering the years 2012-2014 (Electrophoresis 2015, 36, 212-224), recent CE
      MS strategies developed for metabolomics covering the literature from July 2014
      to June 2016 are outlined. Attention will be paid to new CE-MS approaches for the
      profiling of anionic metabolites and the potential of SPE coupled to CE-MS is
      also demonstrated. Representative examples illustrate the applicability of CE-MS
      in the fields of biomedical, clinical, microbial, plant, and food metabolomics. A
      complete overview of recent CE-MS-based metabolomics studies is given in a table,
      which provides information on sample type and pretreatment, capillary coatings,
      and MS detection mode. Finally, general conclusions and perspectives are given.

PMID- 27718259
TI  - Copper as an antibacterial material in different facilities.
AB  - : The present study was performed in real life settings in different facilities
      (hospital, kindergarten, retirement home, office building) with copper and copper
      alloy touch surface products (floor drain lids, toilet flush buttons, door
      handles, light switches, closet touch surfaces, corridor hand rails, front door
      handles and toilet support rails) in parallel to reference products. Pure copper
      surfaces supported lower total bacterial counts (16 +/- 45 vs 105 +/- 430 CFU cm
      2 , n = 214, P < 0.001) and a lower occurrence of Staphylococcus aureus (2.6 vs
      14%, n = 157, P < 0.01) and Gram-negatives (21 vs 34%, n = 214, P < 0.05)
      respectively than did reference surfaces, whereas the occurrence of enterococci
      (15%, n = 214, P > 0.05) was similar. The studied products could be assigned to
      three categories according to their bacterial loads as follows (P < 0.001): floor
      drain lids (300 +/- 730 CFU cm-2 , n = 32), small area touch surfaces (8.0 +/-
      7.1 to 62 +/- 160 CFU cm-2 , n = 90) and large area touch surfaces (1.1 +/- 1.1
      to 1.7 +/- 2.4 CFU cm-2 , n = 92). In conclusion, copper touch surface products
      can function as antibacterial materials to reduce the bacterial load, especially
      on frequently touched small surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      efficiency of copper as an antimicrobial material has been noted in laboratory
      studies and in the hospital environment. The present study further shows that
      copper exerted an antibacterial effect in different facilities, i.e. in a
      hospital, a kindergarten, an office building and in a retirement home for the
      elderly. The study suggests that copper has potential use as an antibacterial
      material and therefore might serve as a means to lower the incidence of
      transmission of infectious agents from inanimate surfaces in different
      facilities, with everyday functions.

PMID- 27718258
TI  - Zinc oxide nanoparticles as a novel anticancer approach; in vitro and in vivo
      evidence.
AB  - Currently, the outcomes of conventional chemotherapeutic approaches are
      unsatisfactory. Clinical application of nanoparticles seems promising. We aim to
      evaluate the possible antitumor activity of zinc oxide nanoparticles (ZnONPs) as
      a chemotherapeutic approach in in vitro and in vivo experimental models. An in
      vitro study was performed on three different cell lines, namely human
      hepatocellular carcinoma (HEPG2), human prostate cancer (PC3), and none-small
      cell lung cancer (A549) cell lines. An in vivo study using diethylnitrosamine
      (DENA)-induced HCC in adult male Wistar rats was conducted to investigate the
      potential antitumor activity of ZnONPs in HCC and the possible underlying
      mechanisms. Hepatocellular carcinoma (HCC) was induced by oral administration of
      DENA given in drinking water (100 mg/L) for 8 weeks. Rats were allocated into
      four groups, namely a control group, an HCC control group receiving DENA alone, a
      ZnONPs (10 MUg/kg per week, intravenous (i.v.) for 1 month) control group, and a
      ZnONPs treatment group (receiving ZnONPs + DENA). ZnONPs significantly reduced
      the elevated serum levels of HCC-related tumor markers alphafetoprotein and alpha
      l-fucosidase and the apoptotic marker caspase-3 compared with the untreated HCC
      rats. In addition, treatment with ZnONPs significantly decreased the elevated
      levels of hepatocyte integrity and oxidative stress markers as compared with the
      untreated HCC control group. Furthermore, the histopathological study revealed
      anaplasia and fibrous degenerations which were significantly corrected by ZnONPs
      treatment. In conclusion, administration of ZnONPs exhibited a promising
      preclinical anticancer efficacy in HCC and could be considered as a novel
      strategy for the treatment HCC in clinical practices.

PMID- 27718260
TI  - Hybrid microfluidics combined with active and passive approaches for continuous
      cell separation.
AB  - Microfluidics, which is classified as either active or passive, is capable of
      separating cells of interest from a complex and heterogeneous sample. Active
      methods utilise external fields such as electric, magnetic, acoustic, and optical
      to drive cells for separation, while passive methods utilise channel structures,
      intrinsic hydrodynamic forces, and steric hindrances to manipulate cells.
      However, when processing complex biological samples such as whole blood with rare
      cells, separation with a single module microfluidic device is difficult. Hybrid
      microfluidics is an emerging technique, which utilises active and passive methods
      whilst fulfilling higher requirements for stable performance, versatility, and
      convenience, including (i) the ability to process multi-target cells, (ii)
      enhanced ability for multiplexed separation, (iii) higher sensitivity, and (iv)
      tunability for a wider operational range. This review introduces the fundamental
      physics and typical formats for subclasses of hybrid microfluidic devices based
      on their different physical fields; presents current examples of cell sorting to
      highlight the advantage and usefulness of hybrid microfluidics on biomedicine,
      and then discusses the challenges and perspective of future development and the
      promising direction of research in this field.

PMID- 27718261
TI  - Tolerance in clinical liver transplantation: The long road ahead.

PMID- 27718262
TI  - A 12-week, randomized, parallel-group, proof-of-concept study of tulobuterol
      patch and salmeterol inhaler as add-on therapy in adult-onset mild-to-moderate
      asthma.
AB  - Patch formulation of tulobuterol has been used in asthma treatment as a long
      acting beta2 -agonist (LABA) through sustained skin absorption. Its treatment
      efficacy, especially in small airways, remains poorly understood. The study aim
      was to investigate LABA add-on effects of tulobuterol patch (TP) and salmeterol
      inhaler (SA) on pulmonary function, asthma control and health status. Patients
      who had adult-onset under-control asthma, despite taking inhaled corticosteroids,
      were enrolled in a randomized, open-label, parallel-group, proof-of-concept study
      of 12-week add-on treatment with TP (n=16) or SA (n=17). Spirometry, impulse
      oscillometry (IOS), exhaled nitric oxide levels, and clinical questionnaires of
      asthma control, health status (St. George's Respiratory Questionnaire: SGRQ), and
      symptoms were evaluated every 4 weeks. Add-on treatment of SA significantly
      improved the spirometric indices of small airway obstruction (forced expiratory
      flow between 25% and 75% of FVC: FEF25-75 , and maximum expiratory flow at 25% of
      FVC: MEF25 ) and IOS indices of whole respiratory resistance (resistance at 5 Hz)
      as compared to TP. In intra-group comparisons, add-on treatment of TP improved
      the scores of the asthma control test and the total SGRQ, as well as the symptom
      and impact components of the SGRQ. SA add-on treatment improved FEV1 and IOS
      parameters of resistance at 20 Hz and reactance at 5 Hz. Neither of the
      treatments improved exhaled nitric oxide levels. In conclusion, add-on treatment
      of TP improved asthma control and health status, whereas SA improved pulmonary
      function measures associated with large and small airway involvement among
      patients with adult-onset mild-to-moderate asthma.

PMID- 27718263
TI  - Short-wave therapy for spontaneous pneumothorax: A case report.

PMID- 27718264
TI  - Rapid QM/MM approach for biomolecular systems under periodic boundary conditions:
      Combination of the density-functional tight-binding theory and particle mesh
      Ewald method.
AB  - A quantum mechanical/molecular mechanical (QM/MM) approach based on the density
      functional tight-binding (DFTB) theory is a useful tool for analyzing chemical
      reaction systems in detail. In this study, an efficient QM/MM method is developed
      by the combination of the DFTB/MM and particle mesh Ewald (PME) methods. Because
      the Fock matrix, which is required in the DFTB calculation, is analytically
      obtained by the PME method, the Coulomb energy is accurately and rapidly
      computed. For assessing the performance of this method, DFTB/MM calculations and
      molecular dynamics simulation are conducted for a system consisting of two
      amyloid-beta(1-16) peptides and a zinc ion in explicit water under periodic
      boundary conditions. As compared with that of the conventional Ewald summation
      method, the computational cost of the Coulomb energy by utilizing the present
      approach is drastically reduced, i.e., 166.5 times faster. Furthermore, the
      deviation of the electronic energy is less than 10-6 Eh. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27718265
TI  - Does fingerprinting truly represent the diversity of wine yeasts? A case study
      with interdelta genotyping of Saccharomyces cerevisiae strains.
AB  - : Simple and efficient genotyping methods are widely used to assess the diversity
      of a large number of microbial strains, e.g. wine yeasts isolated from a specific
      geographical area or a vintage. Such methods are often also the first to be
      applied, to decrease the number of strains deemed interesting for a more time
      consuming physiological characterization. Here, we aimed to use a physiologically
      characterized strain collection of 69 Saccharomyces cerevisiae strains from
      Hungarian wine regions to determine whether geographical origin or physiological
      similarity can be recovered by clustering the strains with one or two
      simultaneously used variations of interdelta genotyping. Our results indicate
      that although a detailed clustering with high resolution can be achieved with
      this method, the clustering of strains is largely contrasting when different
      primer sets are used and it does not recover geographical or physiological
      groups. SIGNIFICANCE AND IMPACT OF THE STUDY: Genotyping is routinely used for
      assessing the diversity of a large number of isolates/strains of a single
      species, e.g. a collection of wine yeasts. We tested the efficiency of interdelta
      genotyping on a collection of Saccharomyces wine yeasts from four wine regions of
      Hungary that was previously characterized physiologically. Interdelta
      fingerprinting recovered neither physiological nor geographical similarities, and
      in addition, the two different primer pairs widely used for this method showed
      conflicting and barely comparable results. Thus, this method does not necessarily
      represent the true diversity of a strain collection, but detailed clustering may
      be achieved by the combined use of primer sets.

PMID- 27718266
TI  - The Influenza A Virus Non-structural Protein NS1 Upregulates The Expression of
      Collagen Triple Helix Repeat Containing 1 Protein.
AB  - Influenza A virus (IAV) infection induces a strong immune response and regulates
      the expression of many host proteins. The collagen triple helix repeat containing
      1 (CTHRC1) protein is a secreted protein that exhibits increased expression
      during the viral infection process. However, the regulatory function of IAV on
      CTHRC1 expression is obscure. In this study, we investigated the effect of IAV on
      CTHRC1 expression and its regulatory mechanism. A total of 106 serum specimens
      from healthy people and 80 serum specimens from patients infected with IAV were
      collected. The CTHRC1 levels in the sera from the IVA patients and healthy
      individuals were measured using an enzyme-linked immunosorbent assay (ELISA), and
      the differences were statistically analysed. A549 cells were infected with the
      IAV or delNS1 virus. Additionally, A549 cells were cotransfected with a
      eukaryotic non-structural NS1 protein gene expression plasmid and the CTHRC1 gene
      promoter reporter plasmid (pCTHRC1-Luc), and, the luciferase activities were
      assessed. The CTHRC1 mRNA and protein expression were detected using reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blotting,
      respectively. The serum CTHRC1 level was significantly higher in the IAV patients
      than in the healthy individuals. IAV upregulated the CTHRC1 mRNA and protein
      expression. The non-structural NS1 protein specifically activated CTHRC1 gene
      promoter activity and upregulated CTHRC1 mRNA and protein expression. The
      activation function had a dose-dependent effect, indicating that influenza virus
      upregulated CTHRC1 expression through its NS1 protein.

PMID- 27718268
TI  - Rank aggregation of local expert knowledge for conservation planning of the
      critically endangered saola.
AB  - There has been much recent interest in using local knowledge and expert opinion
      for conservation planning, particularly for hard-to-detect species. Although it
      is possible to ask for direct estimation of quantities such as population size,
      relative abundance is easier to estimate. However, an expert's knowledge is often
      geographically restricted relative to the area of interest. Combining (or
      aggregating) experts' assessments of relative abundance is difficult when each
      expert only knows a part of the area of interest. We used Google's PageRank
      algorithm to aggregate ranked abundance scores elicited from local experts
      through a rapid rural-appraisal method. We applied this technique to conservation
      planning for the saola (Pseudoryx nghetinhensis), a poorly known bovid. Near a
      priority landscape for the species, composed of 3 contiguous protected areas, we
      asked groups of local people to indicate relative abundances of saola and other
      species by placing beans on community maps. For each village, we used this
      information to rank areas within the knowledge area of that village for saola
      abundance. We used simulations to compare alternative methods to aggregate the
      rankings from the different villages. The best-performing method was then used to
      produce a single map of relative abundance across the entire landscape, an area
      larger than that known to any one village. This map has informed prioritization
      of surveys and conservation action in the continued absence of direct information
      about the saola.

PMID- 27718267
TI  - The recombinant protein rSP03B is a valid antigen for screening dog exposure to
      Phlebotomus perniciosus across foci of canine leishmaniasis.
AB  - The frequency of sandfly-host contacts can be measured by host antibody levels
      against sandfly salivary proteins. Recombinant salivary proteins are suggested to
      represent a valid replacement for salivary gland homogenate (SGH); however, it is
      necessary to prove that such antigens are recognized by antibodies against
      various populations of the same species. Phlebotomus perniciosus (Diptera:
      Psychodidae) is the main vector of Leishmania infantum (Trypanosomatida:
      Trypanosomatidae) in southwest Europe and is widespread from Portugal to Italy.
      In this study, sera were sampled from naturally exposed dogs from distant
      regions, including Campania (southern Italy), Umbria (central Italy) and the
      metropolitan Lisbon region (Portugal), where P. perniciosus is the unique or
      principal vector species. Sera were screened for anti-P. perniciosus antibodies
      using SGH and 43-kDa yellow-related recombinant protein (rSP03B). A robust
      correlation between antibodies recognizing SGH and rSP03B was detected in all
      regions, suggesting substantial antigenic cross-reactivity among different P.
      perniciosus populations. No significant differences in this relationship were
      detected between regions. Moreover, rSP03B and the native yellow-related protein
      were shown to share similar antigenic epitopes, as canine immunoglobulin G (IgG)
      binding to the native protein was inhibited by pre-incubation with the
      recombinant form. These findings suggest that rSP03B should be regarded as a
      universal marker of sandfly exposure throughout the geographical distribution of
      P. perniciosus.

PMID- 27718269
TI  - Characterization of human cytochrome P450 mediated bioactivation of amodiaquine
      and its major metabolite N-desethylamodiaquine.
AB  - AIMS: Oxidative bioactivation of amodiaquine (AQ) by cytochrome P450s to a
      reactive quinoneimine is considered as an important mechanism underlying its
      idiosyncratic hepatotoxicity. However, because internal exposure to its major
      metabolite N-desethylamodiaquine (DEAQ) is up to 240-fold higher than AQ,
      bioactivation of DEAQ might significantly contribute to covalent binding. The aim
      of the present study was to compare the kinetics of bioactivation of AQ and DEAQ
      by human liver microsomes (HLM) and to characterize the CYPs involved in
      bioactivation of AQ and DEAQ. METHODS: Glutathione was used to trap reactive
      metabolites formed in incubations of AQ and DEAQ with HLM and recombinant human
      cytochrome P450s (hCYPs). Kinetics of bioactivation of AQ and DEAQ in HLM and
      involvement of hCYPs were characterized by measuring corresponding glutathione
      conjugates (AQ-SG and DEAQ-SG) using a high-performance liquid chromatography
      method. RESULTS: Bioactivation of AQ and DEAQ in HLM both exhibited Michaelis
      Menten kinetics. For AQ bioactivation, enzyme kinetical parameters were Km , 11.5
      +/- 2.0 MUmol l-1 , Vmax , 59.2 +/- 3.2 pmol min-1  mg-1 and CLint , 5.15 MUl min
      1  mg-1 . For DEAQ, parameters for bioactivation were Km , 6.1 +/- 1.3 MUmol l-1
      , Vmax , 5.5 +/- 0.4 pmol min-1  mg-1 and CLint 0.90 MUl min-1  mg-1 .
      Recombinant hCYPs and inhibition studies with HLM showed involvement of CYP3A4,
      CYP2C8, CYP2C9 and CYP2D6 in bioactivation. CONCLUSIONS: The major metabolite
      DEAQ is likely to be quantitatively more important than AQ with respect to
      hepatic exposure to reactive metabolites in vivo. High expression of CYP3A4,
      CYP2C8, CYP2C9, and CYP2D6 may be risk factors for hepatotoxicity caused by AQ
      therapy.

PMID- 27718270
TI  - The impact of surface area, volume, curvature, and Lennard-Jones potential to
      solvation modeling.
AB  - This article explores the impact of surface area, volume, curvature, and Lennard
      Jones (LJ) potential on solvation free energy predictions. Rigidity surfaces are
      utilized to generate robust analytical expressions for maximum, minimum, mean,
      and Gaussian curvatures of solvent-solute interfaces, and define a generalized
      Poisson-Boltzmann (GPB) equation with a smooth dielectric profile. Extensive
      correlation analysis is performed to examine the linear dependence of surface
      area, surface enclosed volume, maximum curvature, minimum curvature, mean
      curvature, and Gaussian curvature for solvation modeling. It is found that
      surface area and surfaces enclosed volumes are highly correlated to each other's,
      and poorly correlated to various curvatures for six test sets of molecules.
      Different curvatures are weakly correlated to each other for six test sets of
      molecules, but are strongly correlated to each other within each test set of
      molecules. Based on correlation analysis, we construct twenty six nontrivial
      nonpolar solvation models. Our numerical results reveal that the LJ potential
      plays a vital role in nonpolar solvation modeling, especially for molecules
      involving strong van der Waals interactions. It is found that curvatures are at
      least as important as surface area or surface enclosed volume in nonpolar
      solvation modeling. In conjugation with the GPB model, various curvature-based
      nonpolar solvation models are shown to offer some of the best solvation free
      energy predictions for a wide range of test sets. For example, root mean square
      errors from a model constituting surface area, volume, mean curvature, and LJ
      potential are less than 0.42 kcal/mol for all test sets. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27718272
TI  - Reply.

PMID- 27718271
TI  - Neuropsychiatric aspects of 22q11.2 deletion syndrome: considerations in the
      prenatal setting.
AB  - Most major neuropsychiatric outcomes of concern to families are not detectable by
      prenatal ultrasound. The introduction of genome-wide chromosomal microarray
      analysis to prenatal clinical diagnostic testing has increased the detection of
      pathogenic 22q11.2 deletions, which cause the most common genomic disorder. The
      recent addition of this and other microdeletions to non-invasive prenatal
      screening methods using cell-free fetal DNA has further propelled interest in
      outcomes. Conditions associated with 22q11.2 deletions include intellect ranging
      from intellectual disability to average, schizophrenia and other treatable
      psychiatric conditions, epilepsy, and early-onset Parkinson's disease. However,
      there is currently no way to predict how severe the lifetime expression will be.
      Available evidence suggests no major role in these neuropsychiatric outcomes for
      the congenital cardiac or most other structural anomalies that may be detectable
      on ultrasound. This article provides an outline of the lifetime neuropsychiatric
      phenotype of 22q11.2 deletion syndrome that will be useful to clinicians involved
      in prenatal diagnosis and related genetic counselling. The focus is on
      information that will be most relevant to two common situations: detection of a
      22q11.2 deletion in a fetus or newborn, and new diagnosis of 22q11.2 deletion
      syndrome in a parent without a previous molecular diagnosis. (c) 2016 John Wiley
      & Sons, Ltd.

PMID- 27718273
TI  - Activation of UPR Signaling Pathway is Associated With the Malignant Progression
      and Poor Prognosis in Prostate Cancer.
AB  - BACKGROUND: Currently, the role of UPR signaling in prostate cancer (PCa) is
      unclear. To evaluate the relationship between UPR signaling pathway and the
      prognosis of PCa, we explored the expression of IRE1, PERK, and ATF6 in tissues.
      METHODS: A total of 160 PCa and 30 benign prostate hyperplasia (BPH) tissues were
      collected. The expression of UPR signaling factors was assessed by
      immunohistochemistry. The staining characteristics were identified and evaluated
      for associations with clinicopathologic parameters, PSA recurrence survival, and
      prostate cancer-specific morality. RESULTS: The expressions of ATF6alpha, PERK,
      and IRE1alpha were significantly associated with Gleason grade, PSA level, T
      stages and M stage, while this association was not significant in N stage.
      Additionally, UPR signaling factors expressed correlatively with each other. In
      further studies, high expression level of UPR signaling factors was usually
      detected in patients who suffered poor prognosis. Patients with positive UPR
      signaling factors meet shorter survival duration both on cancer-specific morality
      and PSA recurrence. Multivariate analysis showed that IRE1alpha (HR = 4.461 95%CI
      = 1.270-15.670 P = 0.020) could be a potential factor in predicting PSA
      recurrence independently. CONCLUSIONS: UPR signaling factors were co-activated
      and activation of UPR signaling was implicated to the malignant progression and
      worse prognosis of PCa. The mechanism and function of UPR signaling in PCa are
      still to be determined. Prostate 77:274-281, 2017. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27718274
TI  - The prognostic value of stromal FK506-binding protein 1 and androgen receptor in
      prostate cancer outcome.
AB  - BACKGROUND: Improving our ability to predict cancer progression and response to
      conservative or radical intent therapy is critical if we are to prevent under or
      over treatment of individual patients. Whereas the majority of solid tumors now
      have a range of molecular and/or immunological markers to help define prognosis
      and treatment options, prostate cancer still relies mainly on histological
      grading and clinical parameters. We have recently reported that androgen receptor
      (AR) expression in stroma inversely associates with prostate cancer-specific
      survival, and that stromal AR reduces metastasis. For this paper, we tested the
      hypothesis that the AR-regulated gene FKBP51 could be used as a marker of AR
      activity to better predict outcome. METHODS: Using immunohistochemistry on a
      cohort of 64 patient-matched benign and malignant prostate tissues, we assessed
      patient outcome by FKBP51 and AR levels. Immunoblot and RT-qPCR were used to
      demonstrate androgen regulation of FKBP51 in primary and primary human prostatic
      fibroblasts and fibroblast cell-lines. RESULTS: As predicted by FKBP51 level,
      high AR activity in cancer stroma was associated with longer median survival
      (1,306 days) compared with high AR alone (699 days), whereas those with low AR
      and/or low FKBP51 did poorly (384 and 338 days, respectively). Survival could not
      be predicted on the basis cancer epithelial AR levels or activity, and was not
      associated with immunoreactivity in patient matched benign tissues. CONCLUSION:
      FKBP51 improves the ability of stromal AR to predict prostate cancer-specific
      mortality. By adding additional immunological assessment, similar to what is
      already in place in a number of other cancers, we could better serve patients
      with prostate cancer in prognosis and informed treatment choices. Prostate 77:185
      195, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27718276
TI  - The great importance of normalization of LC-MS data for highly-accurate non
      targeted metabolomics.
AB  - The non-targeted metabolomics analysis of biological samples is very important to
      understand biological functions and diseases. LC combined with electrospray
      ionization-based MS has been a powerful tool and widely used for metabolomic
      analyses. However, the ionization efficiency of electrospray ionization
      fluctuates for various unexpected reasons such as matrix effects and intraday
      variations of the instrument performances. To remove these fluctuations,
      normalization methods have been developed. Such techniques include increasing the
      sensitivity, separating co-eluting components and normalizing the ionization
      efficiencies. Normalization techniques allow simultaneously correcting of the
      ionization efficiencies of the detected metabolite peaks and achieving
      quantitative non-targeted metabolomics. In this review paper, we focused on these
      normalization methods for non-targeted metabolomics by LC-MS.

PMID- 27718275
TI  - Performance of ZDOCK and IRAD in CAPRI rounds 28-34.
AB  - We report the performance of our protein-protein docking pipeline, including the
      ZDOCK rigid-body docking algorithm, on 19 targets in CAPRI rounds 28-34.
      Following the docking step, we reranked the ZDOCK predictions using the IRAD
      scoring function, pruned redundant predictions, performed energy landscape
      analysis, and utilized our interface prediction approach RCF. In addition, we
      applied constraints to the search space based on biological information that we
      culled from the literature, which increased the chance of making a correct
      prediction. For all but two targets we were able to find and apply biological
      information and we found the information to be highly accurate, indicating that
      effective incorporation of biological information is an important component for
      protein-protein docking. Proteins 2017; 85:408-416. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27718277
TI  - Protective effect of alpha-lipoic acid, aerobic or resistance exercise from
      colitis in second hand smoke exposed young rats.
AB  - The role of second hand smoke (SHS) exposure on ulcerative colitis is not known.
      Our aim was to examine the effects of alpha-lipoic acid (ALA), chronic aerobic
      (AE) or resistance exercise (RE) on SHS exposed rats with colitis. Sprague-Dawley
      male rats (150-200 g, n=54) were selected for colitis induction. Among the
      colitis groups, one group was exposed to SHS (6 d/wk, 4 cigarettes/d) and the
      other was not. The SHS group was divided into subgroups as follows: sedentary; AE
      (swimming; 3 d/wk); and RE (climbing with weight; 3 d/wk). After 5 weeks, colitis
      was induced by intrarectal acetic acid. All groups had subgroups that were given
      subcutaneously ALA (50 mg/kg per day) or vehicle for 3 days. Following
      decapitation, colon tissues were sampled to examine malondialdehyde (MDA) and
      glutathione (GSH) levels, myeloperoxidase (MPO) activity, luminol and lucigenin
      chemiluminenscence, macroscopic scoring and histologic examination. ANOVA and
      Student's t-test were used for statistical analysis. The increased macroscopic
      and microscopic scores, MPO, MDA, luminol and lucigenin measurements in colitis
      and SHS-colitis groups were decreased via ALA (P<.05-.001). AE declined
      macroscopic and microscopic scores, MDA, lucigenin compared to colitis and SHS
      colitis groups (P<.01-.001). RE reduced microscopic score, MPO, MDA, luminol,
      lucigenin (P<.05-.001) that were increased with colitis. Decreased GSH levels
      (P<.01) in the SHS-colitis group approached to control levels when given ALA.
      According to our results SHS and colitis induction increased inflammatory damage.
      SHS did not worsen it more than colitis. Our results suggest that ALA, AE or RE
      might be protective for SHS exposed ulcerative colitis conditions.

PMID- 27718278
TI  - Recommendations for saving mothers' lives in Japan: Report from the Maternal
      Death Exploratory Committee (2010-2014).
AB  - To make recommendations for saving mothers' lives, issues related to maternal
      deaths including diseases, causes, treatments, and hospital and regional systems
      are analyzed by the Maternal Death Exploratory Committee in Japan. In this
      report, we present ten clinical important recommendations based on the analysis
      of maternal deaths between 2010 and 2014 in Japan.

PMID- 27718279
TI  - No evidence for zoonotic hepatitis E virus infection through dairy milk in
      Germany.

PMID- 27718280
TI  - Combined treatment with cervical pessary and vaginal progesterone for the
      prevention of preterm birth: A randomized clinical trial.
AB  - AIM: We compared the effectiveness of a combined treatment involving cervical
      pessary plus vaginal progesterone to vaginal progesterone alone in decreasing the
      rate of preterm birth in women with short cervix in the second gestational
      trimester. METHODS: This prospective, open-label, randomized clinical trial was
      conducted on 144 pregnant women with singleton pregnancy who had a cervical
      length <= 25 mm, at 18-22 gestational weeks (GW). Seventy-three patients were
      assigned to receive 400 mg of daily vaginal progesterone (group A), and 73 to
      receive cervical pessary plus 400 mg of daily vaginal progesterone (group B),
      until the 37th GW. The patients were then followed until delivery. RESULTS: The
      rates of preterm birth were 16.4% in group A and 19.7% in group B, which were not
      statistically different (P = 0.6). There were no statistically significant
      differences in the rates of preterm birth at <37, <34, <32, and <=26 GW between
      participants randomized to each group (P = 0.55). The rates of low-birthweight
      delivery were 17.8% in group A, and 23.9% in group B, which were not
      statistically different (P = 0.36). The rates of premature rupture of membranes,
      chorioamnionitis, the requirement for neonatal intensive care unit admission, and
      fetal and neonatal deaths were similar between the two groups. CONCLUSION: In
      pregnancies with short cervix at mid-pregnancy, combination therapy of cervical
      pessary plus daily vaginal progesterone does not have any additional benefit over
      daily vaginal progesterone alone in reducing the rate of preterm birth and
      adverse pregnancy outcomes.

PMID- 27718281
TI  - Development of the anatomical quality assessment (AQUA) tool for the quality
      assessment of anatomical studies included in meta-analyses and systematic
      reviews.
AB  - Critical appraisal of anatomical studies is essential before the evidence from
      them undergoes meta-epidemiological synthesis. However, no instrument for
      appraising anatomical studies with inherent applicability to different study
      designs is available. We aim to develop a generic yet comprehensive tool for
      assessing the quality of anatomical studies using a formal consensus method. The
      study steering committee formulated an initial conceptual design and generated
      items for a preliminary tool on the basis of a literature review and expert
      opinion. A Delphi procedure was then adopted to assess the validity of the
      preliminary tool. Feedback from the Delphi panelists was used to improve it. The
      Delphi procedure involved 12 experts in anatomical research. It comprised two
      rounds, after which unanimous consensus was reached about the items to be
      included. The preliminary tool consisted of 20 items, which were phrased as
      signaling questions and organized into five domains: 1. Aim and subject
      characteristics, 2. Study design, 3. Characterization of methods, 4. Descriptive
      anatomy, and 5. Results reporting. Each domain was set to end with a risk of bias
      question. Following round 1, some of the items underwent major revision, although
      agreement was reached regarding inclusion of all the domains and signaling
      questions in the preliminary tool. The tool was revised only for minor language
      inaccuracies after round 2. The AQUA Tool was designed to assess the quality and
      reliability of anatomical studies. It is currently undergoing a validation
      process. Clin. Anat. 30:6-13, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27718282
TI  - Into the Andes: multiple independent colonizations drive montane diversity in the
      Neotropical clearwing butterflies Godyridina.
AB  - Understanding why species richness peaks along the Andes is a fundamental
      question in the study of Neotropical biodiversity. Several biogeographic and
      diversification scenarios have been proposed in the literature, but there is
      confusion about the processes underlying each scenario, and assessing their
      relative contribution is not straightforward. Here, we propose to refine these
      scenarios into a framework which evaluates four evolutionary mechanisms: higher
      speciation rate in the Andes, lower extinction rates in the Andes, older
      colonization times and higher colonization rates of the Andes from adjacent
      areas. We apply this framework to a species-rich subtribe of Neotropical
      butterflies whose diversity peaks in the Andes, the Godyridina (Nymphalidae:
      Ithomiini). We generated a time-calibrated phylogeny of the Godyridina and fitted
      time-dependent diversification models. Using trait-dependent diversification
      models and ancestral state reconstruction methods we then compared different
      biogeographic scenarios. We found strong evidence that the rates of colonization
      into the Andes were higher than the other way round. Those colonizations and the
      subsequent local diversification at equal rates in the Andes and in non-Andean
      regions mechanically increased the species richness of Andean regions compared to
      that of non-Andean regions ('species-attractor' hypothesis). We also found
      support for increasing speciation rates associated with Andean lineages. Our work
      highlights the importance of the Andean slopes in repeatedly attracting non
      Andean lineages, most likely as a result of the diversity of habitats and/or host
      plants. Applying this analytical framework to other clades will bring important
      insights into the evolutionary mechanisms underlying the most species-rich
      biodiversity hotspot on the planet.

PMID- 27718283
TI  - Reproducibility and transparency in biomedical sciences.

PMID- 27718284
TI  - Two new mini-slings compared with transobturator tension-free vaginal tape for
      treatment of stress urinary incontinence: A 1-year follow-up randomized
      controlled trial.
AB  - AIM: The aim of this study was to compare the outcome of two single-incision mini
      slings (the Contasure-Needleless [C-NDL] and the endopelvic free anchorage) with
      the standard midurethral transobturator tension-free vaginal tape (TVT-O)
      procedure. METHODS: A double blind randomized controlled study was conducted at
      Ain Shams University Maternity Hospital from August 2014 until July 2015. A total
      of 209 patients were randomized into three groups. The first group underwent the
      TVT-O procedure, the second group underwent the endopelvic free anchorage
      procedure and the third group underwent the C-NDL procedure. Patients were
      followed up for 12 months in terms of subjective cure, objective cure, and
      complications rate. RESULTS: After 12 months of follow-up, there were no
      differences among the three groups in terms of objective cure rate, subjective
      cure rate, patient satisfaction, or incidence of complications (de novo urge,
      hemorrhage, infection, and mesh erosion). The C-NDL was associated with a shorter
      operative time (P < 0.001) and less blood loss (P = 0.021) than the standard TVT
      O. CONCLUSION: The new single-incision mini-slings showed similar efficacy and
      patient acceptance to that of the standard TVT-O for up to 12 months
      postoperatively with no difference in the complications rate. The C-NDL is
      associated with shorter operative time and less blood loss.

PMID- 27718285
TI  - Concealed heterotopic pregnancy at 12 weeks, with no coexisting risk factors:
      Lessons to be learned.
AB  - A woman presented at the gynecological emergency clinic with severe lower
      abdominal pain. Even though she reported normal menses and had no risk factors
      for ectopic pregnancy, pregnancy test was positive and vaginal sonogram indicated
      heterotopic pregnancy at 12 weeks of gestation, with rupture of the ectopic
      pregnancy. Laboratory results indicated significant blood loss, and emergency
      laparotomy with salpingo-ophorectomy was performed. The intrauterine pregnancy
      continued uneventfully. Interestingly, the previous month the patient had also
      undergone investigation for vague abdominal pain and anemia. This case, apart
      from being very interesting because of the rarity of naturally occurring
      heterotopic pregnancy, shows how a number of factors in patient management and
      investigation, when combined with rare and uncommon conditions, can lead to
      incorrect diagnosis with the associated implications for patient safety. This
      case therefore demonstrates the need for improved patient care and outcome.

PMID- 27718286
TI  - Abdominal ectopic pregnancy with undetectable serum beta-human chorionic
      gonadotropin 9 days following blastocyst transfer.
AB  - With the availability of the highly sensitive beta-human chorionic gonadotropin
      (beta-hCG) assays, all pregnancies, including ectopic pregnancies (EP), are
      expected to have detectable serum beta-hCG at 4 weeks' gestation or 9 days
      following blastocyst transfer. To our knowledge, this is the first report of a
      woman who underwent in vitro fertilization, had undetectable serum beta-hCG 9
      days after blastocyst transfer, and was then diagnosed with a ruptured abdominal
      EP and intra-abdominal bleeding 19 days later. This case highlights that the rise
      in serum beta-hCG might be delayed in abdominal EP compared to intrauterine
      pregnancy. This delay should raise the suspicion for EP, thus meriting close
      monitoring. Moreover, in the absence of menstruation, an undetectable serum beta
      hCG 9 days post-blastocyst transfer should prompt beta-hCG measurement in 2-3
      days to avoid the misdiagnosis of an EP.

PMID- 27718287
TI  - Obstetrical management of patients with extra-anatomic vascular bypass grafts due
      to Takayasu arteritis.
AB  - Little is known about the obstetrical management of patients with Takayasu
      arteritis (TA) who have undergone extra-anatomic vascular bypass (EAVB). We
      describe two cases of EAVB. Case 1 underwent EAVB due to renovascular
      hypertension associated with stenosis of the abdominal aorta, and Case 2 due to
      amaurosis fugax episodes associated with stenosis of the brachiocephalic and left
      common carotid arteries. Pregnancy outcomes were favorable for both cases, though
      the original symptoms recurred during the third trimester in each case, possibly
      due to increased blood flow to the pregnant uterus. Neither bypass occlusion nor
      anastomotic aneurysm formation was observed. Pregnancy outcomes of patients with
      EAVB due to TA are favorable, although pregnancies of patients with TA who have
      cardiovascular complications are associated with an increased risk of maternal
      and fetal morbidity. The obstetrical management of these patients, however,
      should include monitoring for complications related to the EAVB.

PMID- 27718289
TI  - C(sp3 )-H Functionalizations Promoted by the Gold Carbene Generated from
      Vinylidenecyclopropanes.
AB  - The gold carbene generated from vinylidenecyclopropanes (VDCPs) can smoothly
      perform a C(sp3 )-H bond insertion reaction, stereoselectively affording the
      intramolecular C(sp3 )-H bond functionalized product, benzoxepine, with syn
      configuration in moderate to good yields under mild conditions. The KIE
      investigation on this bond functionalization partially revealed that the carbene
      insertion step might be rate-determining. Using a chiral gold(I) catalyst, the
      first example on the asymmetric variant of gold carbene insertion into C(sp3 )-H
      bond has been disclosed, giving the desired products with excellent results.

PMID- 27718288
TI  - Usefulness of a management protocol for patients with cervical multicystic
      lesions: A retrospective analysis of 94 cases and the significance of GNAS
      mutation.
AB  - AIM: The proper preoperative diagnosis and management of cervical proliferative
      disorders presenting with multiple cysts, including minimal deviation
      adenocarcinoma (MDA), lobular endocervical glandular hyperplasia (LEGH), and
      nabothian cyst (NC), have not been fully established. We previously proposed a
      management protocol comprising a diagnostic approach using cytology, magnetic
      resonance imaging, and gastric-type mucin and subsequent treatment. We herein
      evaluate the usefulness of this protocol and implications of GNAS mutations in
      LEGH. METHODS: The clinical courses of 94 patients with cervical multicystic
      lesions who visited our hospital between June 1995 and September 2014 were
      retrospectively analyzed. GNAS mutations were investigated in 10 LEGH, five LEGH
      with atypia, and two MDA cases. RESULTS: Of the 94 patients, the conditions of
      10, 59, and 25 were clinically diagnosed as suspicious of MDA or carcinoma (S/O
      MDA-Ca), suspicious of LEGH (S/O LEGH), and NC, respectively. Ten patients each
      with S/O MDA-Ca and S/O LEGH underwent hysterectomy, and the correct ratio for
      diagnosis was 90% (18/20). Of the 42 S/O LEGH cases followed-up for more than 12
      months, three showed an increase in tumor size. After hysterectomy, two were LEGH
      with atypia while one was NC. The GNAS mutation was detected in two cases of LEGH
      with atypia, one of which showed an increase in tumor size during follow-up.
      CONCLUSION: The management protocol we propose herein will be useful. An increase
      in tumor size is important to detect potentially malignant LEGH. GNAS mutations
      may be involved in the tumorigenesis of potentially malignant LEGH.

PMID- 27718291
TI  - "Anatomy does not exclude physiology, but physiology certainly presupposes
      anatomy".

PMID- 27718290
TI  - PKR regulates LPS-induced osteoclast formation and bone destruction in vitro and
      in vivo.
AB  - OBJECTIVE: In this study, we aimed to clarify the precise mechanism underlying
      lipopolysaccharide (LPS)-induced osteoclastogenesis in periodontal disease with a
      special reference to double-stranded RNA-dependent protein kinase (PKR). MATERIAL
      AND METHODS: We dissected the role of PKR in LPS-induced osteoclast
      differentiation and function using primary mouse bone marrow cells and RAW264.7
      pre-osteoclastic cell line. We used a rat experimental periodontitis (PD) model
      induced by ligature placement with a Porphyromonas gingivalis LPS injection (PD
      rat) and analyzed the therapeutic effects of C16, a PKR inhibitor, on bone loss
      in PD rats. RESULTS: Protein kinase is strongly upregulated and phosphorylated by
      LPS in the osteoclasts. The inhibition of PKR suppressed LPS-stimulated
      osteoclast formation and activation. PKR inhibition also suppressed the LPS
      mediated activation of NF-kappaB and MAPK, which are critical pathways for
      osteoclastogenesis. High expressions of PKR were detected in osteoclasts of PD
      rats, and the treatment with C16 effectively prevented alveolar bone destruction
      in PD rats. CONCLUSIONS: PKR plays a pivotal role in LPS-induced bone loss in PD
      and, thus, has potential as a therapeutic target for PD.

PMID- 27718292
TI  - Twenty-four-hour ambulatory blood pressure and heart rate profiles in diagnosing
      orthostatic hypotension in Parkinson's disease and multiple system atrophy.
AB  - BACKGROUND AND PURPOSE: Twenty-four-hour ambulatory blood pressure and heart rate
      monitoring (24-h ABPM) can provide vital information on circadian blood pressure
      (BP) profiles, which are commonly abnormal in Parkinson's disease with and
      without autonomic failure (PD + AF and PD) and multiple system atrophy (MSA).
      Twenty-four-hour ABPM has not been directly compared between these disorders
      regarding cardiovascular autonomic function. Our aim was to determine the
      usefulness of 24-h ABPM with diary compared to head-up tilting (HUT) in
      diagnosing orthostatic hypotension (OH) in these patients. METHODS: Seventy-four
      patients (23 MSA, 18 PD + AF, 33 PD) underwent cardiovascular autonomic screening
      followed by 24-h ABPM with diary. Standing tests were included during 24-h ABPM.
      The sensitivity and specificity in detecting OH from the 24-h ABPM standing test
      were compared with HUT. RESULTS: There was no difference in OH during HUT between
      MSA and PD + AF (P > 0.05). There was a higher proportion of abnormal BP
      circadian rhythms in MSA and PD + AF compared to PD (P < 0.05) but not between
      MSA and PD + AF (P > 0.05). Patients were divided into groups with OH (OH+) and
      without OH (OH-) on HUT. Using the standing test during 24-h ABPM, a systolic BP
      fall of >20 mmHg showed a sensitivity and specificity of 82% and 100% (area under
      the curve 0.91, 95% confidence interval 0.84-0.98) in differentiating OH+ from OH
      . CONCLUSIONS: Parkinson's disease with autonomic failure and MSA patients had
      similar circadian BP patterns suggesting that autonomic dysfunction influences
      abnormal BP circadian patterns similarly in these disorders. The higher
      sensitivity and specificity in detecting OH using a systolic BP fall of >20 mmHg
      compared to a diastolic BP fall of >10 mmHg during the standing test supports its
      usefulness to assess autonomic function in MSA and PD.

PMID- 27718293
TI  - Rupture of the cervix during pregnancy after cervical pessary insertion for
      preventing preterm birth.
AB  - We present a rare case of a complication after pessary insertion during pregnancy
      due to short cervix. A woman in the 35th week of gestation was admitted to the
      Department of Perinatology due to preterm labor. The patient's history revealed
      cervical pessary insertion during the 29th week of pregnancy due to a cervix of
      18 mm in length. Because of threatened preterm labor, the pessary was removed.
      After pessary removal, a rupture of the cervix was diagnosed. Because of active
      labor and cervical rupture, a cesarean section was performed and a healthy
      newborn was delivered. After cesarean section the cervical rupture was sutured.
      Five days after the operation, the patient underwent surgery again due to a
      necrotically changed part of the cervix. This part of the cervix was removed. We
      present this case to emphasize that cervical pessaries can cause serious
      complications during pregnancy. Clinicians should take this into consideration
      before qualifying patients for pessary insertion.

PMID- 27718294
TI  - Expression of anti-Mullerian hormone in two rat models of polycystic ovary
      syndrome.
AB  - AIM: Anti-Mullerian hormone (AMH) levels are two to three times higher in
      patients with polycystic ovary syndrome (PCOS), but the mechanism of increased
      AMH levels in PCOS remains unclear. The purpose of our experiment was to
      investigate a change in AMH levels in two kinds of commonly used rat models and
      to determine an ideal model for future research of AMH in the pathogenesis of
      PCOS. METHODS: Thirty female Sprague Dawley rats were treated using two modeling
      methods: implantation of a levonorgestrel silastic implant or injection with
      sodium prasterone sulfate plus human chorionic gonadotropin (hCG). Rats in the
      control group were implanted with a blank silastic stick. Serum steroid
      concentrations, ovarian morphology and ovarian expression of AMH and AMH-receptor
      II (RII) proteins were determined and their correlations were studied. RESULTS:
      The results from the levonorgestrel and hCG group were closer to those displayed
      by human PCOS patients than the sodium prasterone sulfate and hCG group. Ovarian
      local expression of AMH and AMH-RII was increased in these both models compared
      with the control group; however, an elevation of serum AMH concentration was not
      observed (12.53 +/- 0.99 ng/ml and 13.22 +/- 1.09 ng/ml vs 16.30 +/- 0.98 ng/ml).
      CONCLUSION: The levonorgestrel and hCG model is more suitable for the study of
      PCOS in puberty.

PMID- 27718295
TI  - Mosquitoes host communities of bacteria that are essential for development but
      vary greatly between local habitats.
AB  - Mosquitoes are insects of interest because several species vector disease-causing
      pathogens to humans and other vertebrates. We previously reported that mosquitoes
      from long-term laboratory cultures require living bacteria in their gut to
      develop, but development does not depend on particular species of bacteria. Here,
      we focused on three distinct but interrelated areas of study to better understand
      the role of bacteria in mosquito development by studying field and laboratory
      populations of Aedes aegypti, Aedes albopictus and Culex quinquefasciatus from
      the southeastern United States. Sequence analysis of bacterial 16S rRNA gene
      amplicons showed that bacterial community composition differed substantially in
      larvae from different collection sites, whereas larvae from the same site shared
      similarities. Although previously unknown to be infected by Wolbachia, results
      also indicated that Ae. aegypti from one field site hosted a dual infection.
      Regardless of collection site or factors like Wolbachia infection, however, each
      mosquito species required living bacteria in their digestive tract to develop.
      Results also identified several concerns in using antibiotics to eliminate the
      bacterial community in larvae in order to study its developmental consequences.
      Altogether, our results indicate that several mosquito species require living
      bacteria for development. We also hypothesize these species do not rely on
      particular bacteria because larvae do not reliably encounter the same bacteria in
      the aquatic habitats they develop in.

PMID- 27718296
TI  - Which type of placenta previa requires blood transfusion more frequently? A new
      concept of indiscernible edge total previa.
AB  - AIM: During cesarean section (CS) for placenta previa (PP), the size/area/portion
      of the lower uterine segment occupied by the placenta may affect the bleeding
      amount and the subsequent need for a blood transfusion (BT). We propose a new
      concept, indiscernible edge total PP (IEPP), when vaginal ultrasound does not
      discern the lower placental edge because the placenta covers the visible lower
      segment. We characterized IEPP, focusing on its allogeneic BT requirement.
      METHODS: We classified PP (n = 307) into four types: marginal, partial,
      discernible edge total PP (DEPP) and IEPP: internal ostium (os)-placental edge
      distance measurable or unmeasurable on vaginal ultrasound in DEPP or IEPP,
      respectively. We determined the clinical characteristics according to the four
      types; the relationship between the intraoperative blood loss and os-edge
      distance in DEPP; and risk factors for allogeneic BT. RESULTS: The following were
      significantly higher/larger in cases of IEPP: previous CS; anterior placentation;
      lacunae; elective cesarean hysterectomy; intraoperative blood loss; autologous
      BT; allogeneic BT; intensive care unit admission; and an abnormally invasive
      placenta (AIP). In DEPP, the os-edge distance was weakly correlated with the
      bleeding amount (r = 0.214). Multivariate logistic regression analysis showed
      that previous CS, lacunae, AIP and IEPP were independent risk factors for
      allogeneic BT (odds ratios 3.8, 3.1, 13.8 and 4.6, respectively). After excluding
      patients undergoing hemostatic procedures during CS, IEPP remained the only
      independent risk factor for allogeneic BT (odds ratio 5.2). CONCLUSIONS: The new
      concept of IEPP may be useful for predicting BT in CS for patients with PP.

PMID- 27718297
TI  - TRPA1 receptor is upregulated in human oral lichen planus.
AB  - OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disease of unknown
      etiology with antigen-specific and non-specific mechanisms. Transient receptor
      potential ankyrin 1 (TRPA1) is a non-selective cation channel activated by
      noxious stimuli such as oxidative stress products evoking pain and release of
      proinflammatory mediators from sensory nerve endings culminating in neurogenic
      inflammation. Extraneuronal TRPA1s, for example, on immune cells possess yet
      unknown functions. SUBJECTS AND METHODS: We studied the buccal mRNA expression
      (qPCR) and protein localization (immunohistochemistry) of TRPA1 receptors and key
      OLP mediator transcripts in oral mucosa samples of healthy volunteers (n = 9),
      OLP patients (n = 43), and OLP-like hyperkeratotic patients (n = 12). RESULTS: We
      measured 27.7- and 25.5-fold TRPA1 mRNA increase in OLP and OLP-like
      hyperkeratotic patients compared to healthy controls. TRPA1 transcripts elevated
      2.4-fold in hypertensive OLP but not in hyperkeratotic patients compared to
      counterparts, reduced by 1.6-fold by angiotensin-convertase inhibitor intake.
      TRPA1 messenger RNA was more coexpressed with transcripts of tumor necrosis
      factor alpha than with interferon gamma. Keratinocytes, macrophages but not T
      cells expressed TRPA1. CONCLUSIONS: We provided evidence for the extraneuronal
      presence and upregulation of the proinflammatory TRPA1 receptor in buccal samples
      of patients with OLP. This may implicate the ion channel in the pathomechanism of
      OLP.

PMID- 27718299
TI  - Duration of reproductive lifespan and age at menarche in relation to metabolic
      syndrome in postmenopausal Chinese women.
AB  - AIM: This study aimed to assess the associations between menstrual
      characteristics and the prevalence of metabolic syndrome (MetS) and non-alcoholic
      fatty liver disease. METHODS: A cross-sectional study was conducted with a sample
      of 1625 postmenopausal women in China. Subjects were classified into three groups
      according to the tertiles of some variables related to the reproductive life. We
      assessed associations in multivariable-adjusted analyses, using logistic
      regressions. RESULTS: After adjustments for confounding factors, the odds ratios
      (OR) for predicting the presence of MetS increased gradually: as the years of
      menstruation increased (18-34 years vs 35-37 years vs 38-46 years: OR [95%
      confidence interval (CI)] = 1 vs 1.231 [0.942-1.610] vs 1.309 [0.985-1.740],
      respectively); as age at menopause increased (31-48 years vs 49-51 years vs 52-59
      years: OR [95%CI] = 1 vs 1.115 [0.846-1.469] vs 1.315 [0.986-1.753],
      respectively); and as age at menarche decrease (11-13 years vs 14-15 years vs 16
      20 years: OR [95%CI] = 1 vs 0.950 [0.728-1.240] vs 0.862 [0.610-1.119],
      respectively). Among the components of MetS, the highest tertile of years of
      menstruation was significantly associated with elevated waist circumference (OR
      =1.401 [95%CI = 1.092-1.798]), and elevated triglyceride (OR =1.220 [95%CI =
      0.934-1.593]). Nevertheless, the association between these reproductive factors
      and non-alcoholic fatty liver disease was not significant. CONCLUSION: Longer
      duration of menstruation and earlier age at menarche were significantly
      associated with a higher risk of central obesity and MetS in postmenopausal
      Chinese women.

PMID- 27718300
TI  - Insights into microbial ecosystems using a new computational approach.

PMID- 27718301
TI  - Embolization of the inferior mesenteric artery for post-partum hemorrhage with a
      vaginal laceration: A case with unusual collateral supply.
AB  - A 36-year-old primipara woman was referred to the interventional department for
      management of severe primary post-partum hemorrhage with a vaginal laceration
      after a normal vaginal delivery. Angiography revealed that the superior rectal
      branch of the inferior mesenteric artery was one of the origins of persistent
      vaginal bleeding following embolization of both uterine arteries. The patient was
      successfully treated by selective embolization without other complications. Our
      case report highlights that the inferior mesenteric artery should be considered
      as an unusual extrauterine source for post-partum hemorrhage.

PMID- 27718302
TI  - Evaluation of new markers for minimal residual disease monitoring in B-cell
      precursor acute lymphoblastic leukemia: CD73 and CD86 are the most relevant new
      markers to increase the efficacy of MRD 2016; 00B: 000-000.
AB  - BACKGROUND: Multiparametric flow cytometry (MFC) is a popular technique for
      minimal residual disease (MRD) analysis. However, its applicability is still
      limited to 90% of B-cell precursor acute lymphoblastic leukemia (BCPALL) due to
      two major issues, i.e. a proportion of cases do not express adequate leukemia
      associated immunophenotype (LAIPs) with currently used markers and drug-induced
      antigen modulation. Hence, the incorporation of additional reliable markers is
      required for the further improvement of MFC-based MRD evaluation. We studied the
      utility of new markers in improvising MFC-based MRD detection in BCPALL. METHODS:
      Expression-patterns of six new markers, i.e. CD24, CD44, CD72, CD73, CD86, and
      CD200 were studied in leukemic-blasts from ninety childhood BCPALL patients and
      in hematogones from 20 uninvolved staging bone marrow (BM) and ten postinduction
      non-BCPALL BM samples using eight-color MFC. The utility of these new markers in
      the day 35 postinduction MRD evaluation was determined. RESULTS: Frequencies of
      LAIPs of CD73, CD86, CD72, CD44, CD200, and CD24 in diagnostic samples were 76.7,
      56.7, 55.6, 50, 28.9, and 20%, respectively. Differential expression of all new
      markers was highly significant (P < 0.01) between early (CD10+ CD19+ CD34+)
      hematogones, late (CD10+ CD19+ CD34-) hematogones and BCPALL blasts except
      between early hematogones and BCPALL blasts for CD200 (P = 0.1). In MRD-positive
      samples, CD73 showed the maximum (83%) frequency of LAIP and CD86 showed the
      highest (100%) stability of aberrant expression. Inclusion of CD73 and CD86
      increased the applicability of MFC-MRD assay to 98.9% MRD samples. CONCLUSION:
      CD73 and CD86 are the most relevant markers to incorporate in the routine MRD
      evaluation of BCPALL. (c) 2016 International Clinical Cytometry Society.

PMID- 27718298
TI  - Changes in the detergent-insoluble brain proteome linked to amyloid and tau in
      Alzheimer's Disease progression.
AB  - Despite a key role of amyloid-beta (Abeta) in Alzheimer's disease (AD),
      mechanisms that link Abeta plaques to tau neurofibrillary tangles and cognitive
      decline still remain poorly understood. The purpose of this study was to quantify
      proteins in the sarkosyl-insoluble brain proteome correlated with Abeta and tau
      insolubility in the asymptomatic phase of AD (AsymAD) and through mild cognitive
      impairment (MCI) and symptomatic AD. Employing label-free mass spectrometry-based
      proteomics, we quantified 2711 sarkosyl-insoluble proteins across the prefrontal
      cortex from 35 individual cases representing control, AsymAD, MCI and AD.
      Significant enrichment of Abeta and tau in AD was observed, which correlated with
      neuropathological measurements of plaque and tau tangle density, respectively.
      Pairwise correlation coefficients were also determined for all quantified
      proteins to Abeta and tau, across the 35 cases. Notably, six of the ten most
      correlated proteins to Abeta were U1 small nuclear ribonucleoproteins (U1
      snRNPs). Three of these U1 snRNPs (U1A, SmD and U1-70K) also correlated with tau
      consistent with their association with tangle pathology in AD. Thus, proteins
      that cross-correlate with both Abeta and tau, including specific U1 snRNPs, may
      have potential mechanistic roles in linking Abeta plaques to tau tangle pathology
      during AD progression.

PMID- 27718303
TI  - Is Alcoholics Anonymous religious, spiritual, neither? Findings from 25 years of
      mechanisms of behavior change research.
AB  - BACKGROUND: Alcoholics Anonymous (AA) is a world-wide recovery mutual-help
      organization that continues to arouse controversy. In large part, concerns
      persist because of AA's ostensibly quasi-religious/spiritual orientation and
      emphasis. In 1990 the United States' Institute of Medicine called for more
      studies on AA's effectiveness and its mechanisms of behavior change (MOBC)
      stimulating a flurry of federally funded research. This paper reviews the
      religious/spiritual origins of AA and its program and contrasts its theory with
      findings from this latest research. METHOD: Literature review, summary and
      synthesis of studies examining AA's MOBC. RESULTS: While AA's original main text
      ('the Big Book', 1939) purports that recovery is achieved through quasi
      religious/spiritual means ('spiritual awakening'), findings from studies on MOBC
      suggest this may be true only for a minority of participants with high addiction
      severity. AA's beneficial effects seem to be carried predominantly by social,
      cognitive and affective mechanisms. These mechanisms are more aligned with the
      experiences reported by AA's own larger and more diverse membership as detailed
      in its later social, cognitive and behaviorally oriented publications (e.g.
      Living Sober, 1975) written when AA membership numbered more than a million men
      and women. CONCLUSIONS: Alcoholics Anonymous appears to be an effective clinical
      and public health ally that aids addiction recovery through its ability to
      mobilize therapeutic mechanisms similar to those mobilized in formal treatment,
      but is able to do this for free over the long term in the communities in which
      people live.

PMID- 27718304
TI  - Supporting less experienced physicians to write a paper: A proposal to introduce
      such a system on an academic society basis.

PMID- 27718305
TI  - Mass spectrometry applied to the identification of Mycobacterium tuberculosis and
      biomarker discovery.
AB  - An adequate and effective tuberculosis (TB) diagnosis system has been identified
      by the World Health Organization as a priority in the fight against this disease.
      Over the years, several methods have been developed to identify the bacillus, but
      bacterial culture remains one of the most affordable methods for most countries.
      For rapid and accurate identification, however, it is more feasible to implement
      molecular techniques, taking advantage of the availability of public databases
      containing protein sequences. Mass spectrometry (MS) has become an interesting
      technique for the identification of TB. Here, we review some of the most widely
      employed methods for identifying Mycobacterium tuberculosis and present an update
      on MS applied for the identification of mycobacterial species.

PMID- 27718306
TI  - Common congenital anomalies: Environmental causes and prevention with folic acid
      containing multivitamins.
AB  - Congenital anomalies, congenital defects, or birth defects are significant causes
      of death in infants. The most common congenital defects are congenital heart
      defects (CHDs) and neural tube defects (NTDs). Defects induced by genetic
      mutations, environmental exposure to toxins, or a combination of these effects
      can result in congenital malformations, leading to infant death or long-term
      disabilities. These defects produce significant mortality and morbidity in the
      affected individuals, and families are affected emotional and financially. Also,
      society is impacted on many levels. Congenital anomalies may be reduced by
      dietary supplements of folic acid and other vitamins. Here, we review the
      evidence for specific roles of toxins (alcohol, cigarette smoke) in causing
      common severe congenital anomalies like CHDs, NTDs, and ocular defects. We also
      review the evidence for beneficial effects for dietary supplementation, and
      highlight gaps in our knowledge, where research may contribute to additional
      benefits of intervention that can reduce birth defects. Extensive discussion of
      common severe congenital anomalies (CHDs, NTDs, and ocular defects) illustrates
      the effects of diet on the frequency and severity of these defects. Birth Defects
      Research (Part C) 108:274-286, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27718307
TI  - Sen1, the homolog of human Senataxin, is critical for cell survival through
      regulation of redox homeostasis, mitochondrial function, and the TOR pathway in
      Saccharomyces cerevisiae.
AB  - Mutations in the Senataxin gene, SETX are known to cause the neurodegenerative
      disorders, ataxia with oculomotor apraxia type 2 (AOA2), and amyotrophic lateral
      sclerosis 4 (ALS4). However, the mechanism underlying disease pathogenesis is
      still unclear. The Senataxin N-terminal protein-interaction and C-terminal
      RNA/DNA helicase domains are conserved in the Saccharomyces cerevisiae homolog,
      Sen1p. Using genome-wide expression analysis, we first show alterations in key
      cellular pathways such as: redox, unfolded protein response, and TOR in the yeast
      sen1 DeltaN mutant (N-terminal truncation). This mutant exhibited growth defects
      on nonfermentable carbon sources, was sensitive to oxidative stress, and showed
      severe loss of mitochondrial DNA. The growth defect could be partially rescued
      upon supplementation with reducing agents and antioxidants. Furthermore, the
      mutant showed higher levels of reactive oxygen species, lower UPR activity, and
      alterations in mitochondrial membrane potential, increase in vacuole acidity,
      free calcium ions in the cytosol, and resistance to rapamycin treatment. Notably,
      the sen1 ?N mutant showed increased cell death and shortened chronological life
      span. Given the strong similarity of the yeast and human Sen1 proteins, our study
      thus provides a mechanism for the progressive neurological disorders associated
      with mutations in human senataxin.

PMID- 27718308
TI  - Digestive fate of dietary carrageenan: Evidence of interference with digestive
      proteolysis and disruption of gut epithelial function.
AB  - SCOPE: The objective of this study was to interrogate two mechanisms by which
      commercial Carrageenans (E407) (CGN) may adversely affect human health: (i)
      Through modification of gastric proteolysis and (ii) Through affecting gut
      epithelial structure and function. METHODS AND RESULTS: Three commercial CGN
      samples with distinct zeta-potentials (stable at the pH range of 3-7 and varied
      with physiological levels of CaCl2 ) were mixed with milk, soy or egg protein
      isolates, then subjected to a semi-dynamic in vitro digestion model and analyzed
      by SDS-PAGE. This revealed varying levels of interference with gastric digestive
      proteolysis and a significant decrease in pepsin activity. Further, a Caco-2 cell
      model was used to explore various effects of physiologically digested CGN (pdCGN)
      on various epithelial cell functions and characteristics. Samples of pdCGN (0.005
      0.5 mg/mL) affected the epithelial barrier function, including redistribution of
      the tight-junction protein Zonula Occludens (Zo)-1, changes in cellular F-actin
      architecture and increased monolayer permeability to the transfer of
      macromolecules. Moreover, pdCGN induced elevation in the levels of the pro
      inflammatory IL-8 receptor CXCR1. CONCLUSION: This work raises the possibility
      that CGN may reduce protein and peptide bioaccessibility, disrupt normal
      epithelial function, promote intestinal inflammation, and consequently compromise
      consumer health.

PMID- 27718309
TI  - Band 3 nullVIENNA , a novel homozygous SLC4A1 p.Ser477X variant causing severe
      hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis.
AB  - We describe the second patient with anionic exchanger 1/band 3 null phenotype
      (band 3 nullVIENNA ), which was caused by a novel nonsense mutation c.1430C>A
      (p.Ser477X) in exon 12 of SLC4A1. We also update on the previous band 3
      nullCOIMBRA patient, thereby elucidating the physiological implications of total
      loss of AE1/band 3. Besides transfusion-dependent severe hemolytic anemia and
      complete distal renal tubular acidosis, dyserythropoiesis was identified in the
      band 3 nullVIENNA patient, suggesting a role for band 3 in erythropoiesis.
      Moreover, we also, for the first time, report that long-term survival is possible
      in band 3 null patients.

PMID- 27718310
TI  - Protection against vaccine preventable diseases in children treated for acute
      lymphoblastic leukemia.
AB  - BACKGROUND: The objective of this retrospective study was to assess protection
      against vaccine preventable diseases (VPDs) in children treated for acute
      lymphoblastic leukemia (ALL). PROCEDURE: Clinical characteristics and vaccination
      records were collected. Antibodies against VPDs were measured after completion of
      chemotherapy and after a booster dose of vaccine. Immunization status of
      household members was evaluated. RESULTS: Sixty children were included. Median
      interval between the end of chemotherapy and enrolment in the study was 13 months
      (range 1-145). At ALL diagnosis, 81.3% of the children were up to date with their
      vaccination schedule. This proportion decreased to 52.9% at enrolment. Among the
      parents, 21% were up to date with their immunization schedule and 42% had
      received seasonal influenza vaccination. After chemotherapy, less than 50% of the
      patients were seroprotected against tetanus, diphtheria, polio 3, Haemophilus
      influenzae type b (Hib), and mumps and no more than 80% were seroprotected
      against polio 1 and 2, measles, rubella, and varicella. After a booster dose of
      vaccine, the rate of protection increased to over 90% for each of the following
      antigens: TT, DT, polio 1, Hib, measles, and rubella. Nevertheless, polio 3,
      mumps, and varicella-zoster virus antibodies titers/concentrations remained below
      seroprotective thresholds in over 20% of the patients. CONCLUSIONS: After
      chemotherapy for ALL, most of the children were not protected against VPDs. As
      the majority mounted a robust response to booster vaccines, efforts need to be
      done to improve protection against VPDs by implementing a systematic vaccine
      booster schedule. This could also be helped by reinforcing household members'
      immunization.

PMID- 27718311
TI  - A rice jacalin-related mannose-binding lectin gene, OsJRL, enhances Escherichia
      coli viability under high salinity stress and improves salinity tolerance of
      rice.
AB  - Salinity, which is one of the most common abiotic stresses, may severely affect
      plant productivity and quality. Although plant lectins are thought to play
      important roles in plant defense signaling during pathogen attack, little is
      known about the contribution of plant lectins to stress resistance. We cloned and
      functionally characterized a rice jacalin-related mannose-binding lectin gene,
      OsJRL, from rice 'Nipponbare'. We analyzed the expression patterns of OsJRL under
      various stress conditions in rice. Furthermore, we overexpressed OsJRL in
      Escherichia coli and rice. The cDNA of OsJRL contained a 438 bp open reading
      frame, which encodes a polypeptide of 145 amino acids. OsJRL was localized in the
      nucleus and cytoplasm. Real time PCR analyses revealed that OsJRL expression
      showed tissue specificity in rice and was upregulated under diverse stresses,
      namely salt, drought, cold, heat and abscisic acid treatments. Overexpression of
      OsJRL in E. coli enhanced cell viability and dramatically improved tolerance of
      high salinity. Overexpression of OsJRL in rice also enhanced salinity tolerance
      and increased the expression levels of a number of stress-related genes,
      including three LEA (late embryogenesis abundant proteins) genes (OsLEA19a,
      OsLEA23 and OsLEA24), three Na+ transporter genes (OsHKT1;3, OsHKT1;4 and
      OsHKT1;5) and two DREB genes (OsDREB1A and OsDREB2B). Based on these results, we
      suggest that OsJRL plays an important role in cell protection and stress signal
      transduction.

PMID- 27718312
TI  - Extracting histones for the specific purpose of label-free MS.
AB  - Extracting histones from cells is the first step in studies that aim to
      characterize histones and their post-translational modifications (hPTMs) with MS.
      In the last decade, label-free quantification is more frequently being used for
      MS-based histone characterization. However, many histone extraction protocols
      were not specifically designed for label-free MS. While label-free quantification
      has its advantages, it is also very susceptible to technical variation. Here, we
      adjust an established histone extraction protocol according to general label-free
      MS guidelines with a specific focus on minimizing sample handling. These
      protocols are first evaluated using SDS-PAGE. Hereafter, a selection of
      extraction protocols was used in a complete histone workflow for label-free MS.
      All protocols display nearly identical relative quantification of hPTMs. We thus
      show that, depending on the cell type under investigation and at the cost of some
      additional contaminating proteins, minimizing sample handling can be done during
      histone isolation. This allows analyzing bigger sample batches, leads to reduced
      technical variation and minimizes the chance of in vitro alterations to the hPTM
      snapshot. Overall, these results allow researchers to determine the best protocol
      depending on the resources and goal of their specific study. Data are available
      via ProteomeXchange with identifier PXD002885.

PMID- 27718313
TI  - Abscisic acid regulates seed germination of Vellozia species in response to
      temperature.
AB  - The relationship between the phytohormones, gibberellin (GA) and abscisic acid
      (ABA) and light and temperature on seed germination is still not well understood.
      We aimed to investigate the role of the ABA and GA on seed germination of
      Vellozia caruncularis, V. intermedia and V. alutacea in response to light/dark
      conditions on different temperature. Seeds were incubated in GA (GA3 or GA4 ) or
      ABA and their respective biosynthesis inhibitors (paclobutrazol - PAC, and
      fluridone - FLU) solutions at two contrasting temperatures (25 and 40  degrees
      C). Furthermore, endogenous concentrations of active GAs and those of ABA were
      measured in seeds of V. intermedia and V. alutacea during imbibition/germination.
      Exogenous ABA inhibited the germination of Vellozia species under all conditions
      tested. GA, FLU and FLU + GA3 stimulated germination in the dark at 25  degrees C
      (GA4 being more effective than GA3 ). PAC reduced seed germination in V.
      caruncularis and V. alutacea, but did not affect germination of V. intermedia at
      40  degrees C either under light or dark conditions. During imbibition in the
      dark, levels of active GAs decreased in the seeds of V. intermedia, but were not
      altered in those of V. alutacea. Incubation at 40  degrees C decreased ABA levels
      during imbibition in both V. caruncularis and V. alutacea. We conclude that the
      seeds of Vellozia species studied here require light or high temperature to
      germinate and ABA has a major role in the regulation of Vellozia seed germination
      in response to light and temperature.

PMID- 27718314
TI  - The assessment of data sources for influenza virologic surveillance in New York
      State.
AB  - BACKGROUND: Following the 2013 USA release of the Influenza Virologic
      Surveillance Right Size Roadmap, the New York State Department of Health (NYSDOH)
      embarked on an evaluation of data sources for influenza virologic surveillance.
      OBJECTIVE: To assess NYS data sources, additional to data generated by the state
      public health laboratory (PHL), which could enhance influenza surveillance at the
      state and national level. METHODS: Potential sources of laboratory test data for
      influenza were analyzed for quantity and quality. Computer models, designed to
      assess sample sizes and the confidence of data for statistical representation of
      influenza activity, were used to compare PHL test data to results from clinical
      and commercial laboratories, reported between June 8, 2013 and May 31, 2014.
      RESULTS: Sample sizes tested for influenza at the state PHL were sufficient for
      situational awareness surveillance with optimal confidence levels, only during
      peak weeks of the influenza season. Influenza data pooled from NYS PHLs and
      clinical laboratories generated optimal confidence levels for situational
      awareness throughout the influenza season. For novel influenza virus detection in
      NYS, combined real-time (rt) RT-PCR data from state and regional PHLs achieved
      >=85% confidence during peak influenza activity, and >=95% confidence for most of
      low season and all of off-season. CONCLUSIONS: In NYS, combined data from
      clinical, commercial, and public health laboratories generated optimal influenza
      surveillance for situational awareness throughout the season. Statistical
      confidence for novel virus detection, which is reliant on only PHL data, was
      achieved for most of the year.

PMID- 27718315
TI  - Comparison by multilocus variable-number tandem repeat analysis and antimicrobial
      resistance among atypical enteropathogenic Escherichia coli strains isolated from
      food samples and human and animal faecal specimens.
AB  - AIM: This study assessed whether multilocus variable-number tandem repeat
      analysis (MLVA) and antimicrobial susceptibility testing discriminated
      diarrhoeagenic atypical enteropathogenic Escherichia coli (aEPEC) from aEPEC
      indigenous to domestic animals or healthy people. METHODS AND RESULTS: MLVA
      genotyping of 142 aEPEC strains isolated from foods and faecal samples of
      domestic animals and humans revealed 126 distinct MLVA profiles that distributed
      to four clusters, yielding a Simpson's index of diversity (D) of 99.8%. Cluster 2
      included 87% of cattle isolates and 67% of patient isolates. The plurality
      (15/34, 44%) of strains from healthy humans mapped to Cluster 1, while half
      (18/41, 44%) of the swine strains belonged to Cluster 4. Testing for
      antimicrobial susceptibility revealed that 52 strains (37%) of aEPEC were
      resistant to one or more agents; only 10 strains (7%) exhibited resistance to
      more than three agents. Strains isolated from swine or food exhibited a wider
      variety of resistance phenotypes than bovine or human strains. CONCLUSIONS: MLVA
      assigned the aEPEC isolates from cattle and patients to Cluster 2, distinct from
      aEPEC from other sources. Hog yards may be a larger source of drug-resistant
      strains than are cattle ranches. SIGNIFICANCE AND IMPACT OF THE STUDY: MLVA
      suggests that human diarrhoeagenic aEPEC are derived from cattle and are distinct
      from strains carried by healthy people and other animals. Cattle appear to be
      reservoirs of human diarrhoeagenic aEPEC.

PMID- 27718316
TI  - Development of genomic tools in a widespread tropical tree, Symphonia globulifera
      L.f.: a new low-coverage draft genome, SNP and SSR markers.
AB  - Population genetic studies in tropical plants are often challenging because of
      limited information on taxonomy, phylogenetic relationships and distribution
      ranges, scarce genomic information and logistic challenges in sampling. We
      describe a strategy to develop robust and widely applicable genetic markers based
      on a modest development of genomic resources in the ancient tropical tree species
      Symphonia globulifera L.f. (Clusiaceae), a keystone species in African and
      Neotropical rainforests. We provide the first low-coverage (11X) fragmented draft
      genome sequenced on an individual from Cameroon, covering 1.027 Gbp or 67.5% of
      the estimated genome size. Annotation of 565 scaffolds (7.57 Mbp) resulted in the
      prediction of 1046 putative genes (231 of them containing a complete open reading
      frame) and 1523 exact simple sequence repeats (SSRs, microsatellites). Aligning a
      published transcriptome of a French Guiana population against this draft genome
      produced 923 high-quality single nucleotide polymorphisms. We also preselected
      genic SSRs in silico that were conserved and polymorphic across a wide
      geographical range, thus reducing marker development tests on rare DNA samples.
      Of 23 SSRs tested, 19 amplified and 18 were successfully genotyped in four S.
      globulifera populations from South America (Brazil and French Guiana) and Africa
      (Cameroon and Sao Tome island, FST  = 0.34). Most loci showed only population
      specific deviations from Hardy-Weinberg proportions, pointing to local population
      effects (e.g. null alleles). The described genomic resources are valuable for
      evolutionary studies in Symphonia and for comparative studies in plants. The
      methods are especially interesting for widespread tropical or endangered taxa
      with limited DNA availability.

PMID- 27718317
TI  - The development of SRM assays is transforming proteomics research.
AB  - Bottom-up targeted proteomics using SRM is a powerful analytical technology, but
      it requires the development of SRM assays, which is a complex procedure. Whereas
      proteome-wide SRM assays have recently been developed for a small number of
      species, this is not so for the mouse. In this issue, Percy et al. report the
      development of hundreds of mouse SRM assays. Their development required shotgun
      MS to identify proteotypic peptides, synthesis, and LC-MS characterization of
      peptide standards, and interlaboratory SRM to robustly assess the quality of the
      assays. The resulting SRM assays are intended to be used to analyze mouse plasma
      and cardiac tissue, primarily for cardiovascular disease and cancer research.

PMID- 27718318
TI  - Local paleoenvironmental controls on the carbon-isotope record defining the
      Bitter Springs Anomaly.
AB  - Large magnitude (>100/00) carbon-isotope (delta13 C) excursions recorded in
      carbonate-bearing sediments are increasingly used to monitor environmental change
      and constrain the chronology of the critical interval in the Neoproterozoic
      stratigraphic record that is timed with the first appearance and radiation of
      metazoan life. The ~100/00 Bitter Springs Anomaly preserved in Tonian-aged (1000
      720 Ma) carbonate rocks in the Amadeus Basin of central Australia has been
      offered as one of the best preserved examples of a primary marine delta13 C
      excursion because it is regionally reproducible and delta13 C values covary in
      organic and carbonate carbon arguing against diagenetic exchange. However, here
      we show that delta13 C values defining the excursion coincide with abrupt
      lithofacies changes between regularly cyclic grainstone and microbial carbonates,
      and desiccated red bed mudstones with interbedded evaporite and dolomite
      deposits, recording local environmental shifts from restricted marine conditions
      to alkaline lacustrine and playa settings that preserve negative (-40/00) and
      positive (+60/00) delta13 C values, respectively. The stratigraphic delta13 C
      pattern in both organic and carbonate carbon recurs within the basin in a similar
      way to associated sedimentary facies, reflecting the linkage of local
      paleoenvironmental conditions and delta13 C values. These local excursions may be
      time transgressive or record a relative sea-level influence manifest through
      exposure of sub-basins isolated by sea-level fall below shallow sills, but are
      independent of secular seawater variation. As the shallow intracratonic setting
      of the Bitter Springs Formation is typical of other Neoproterozoic carbonate
      successions used to construct the present delta13 C seawater record, it
      identifies the potential for local influences on delta13 C excursions that are
      neither diagenetic nor representative of the global exogenic cycle.

PMID- 27718319
TI  - Measuring cancer-specific child adjustment difficulties: Development and
      validation of the Children's Oncology Child Adjustment Scale (ChOCs).
AB  - BACKGROUND: Childhood cancer is associated with child adjustment difficulties
      including, eating and sleep disturbance, and emotional and other behavioral
      difficulties. However, there is a lack of validated instruments to measure the
      specific child adjustment issues associated with pediatric cancer treatments. The
      aim of this study was to develop and evaluate the reliability and validity of a
      parent-reported, child adjustment scale. PROCEDURE: One hundred thirty-two
      parents from two pediatric oncology centers who had children (aged 2-10 years)
      diagnosed with cancer completed the newly developed measure and additional
      measures of child behavior, sleep, diet, and quality of life. Children were more
      than 4 weeks postdiagnosis and less than 12 months postactive treatment. Factor
      structure, internal consistency, and construct (convergent) validity analyses
      were conducted. RESULTS: Principal component analysis revealed five distinct and
      theoretically coherent factors: Sleep Difficulties, Impact of Child's Illness,
      Eating Difficulties, Hospital-Related Behavior Difficulties, and General Behavior
      Difficulties. The final 25-item measure, the Children's Oncology Child Adjustment
      Scale (ChOCs), demonstrated good internal consistency (alpha = 0.79-0.91).
      Validity of the ChOCs was demonstrated by significant correlations between the
      subscales and measures of corresponding constructs. CONCLUSION: The ChOCs
      provides a new measure of child adjustment difficulties designed specifically for
      pediatric oncology. Preliminary analyses indicate strong theoretical and
      psychometric properties. Future studies are required to further examine
      reliability and validity of the scale, including test-retest reliability,
      discriminant validity, as well as change sensitivity and generalizability across
      different oncology samples and ages of children. The ChOCs shows promise as a
      measure of child adjustment relevant for oncology clinical settings and research
      purposes.

PMID- 27718320
TI  - Hypertension and early menopause after the use of assisted reproductive
      technologies in women aged 43 years or older: Long-term follow-up study.
AB  - AIM: The aim of this study was to investigate the long-term consequences to
      women's health and the onset of menopause in healthy women of advanced
      reproductive age who conceived by assisted reproductive technologies (ART).
      METHODS: Healthy women who conceived by ART (72) and controls (80) were selected
      among 320 women >= 43 years, who delivered between January 2010 and December 2011
      in the Department of Gynecological and Obstetrical Sciences and Urological
      Sciences of "Sapienza" University of Rome. Body mass index (BMI), systolic blood
      pressure (SBP), diastolic blood pressure (DBP), and presence of hypertension and
      diabetes were analyzed at three days, six months, and three years after delivery.
      The onset of menopause was analyzed after three years. RESULTS: In the ART group,
      SBP, DBP and hypertension were higher at three days, six months, and three years
      after delivery. Menopausal age was significantly lower. CONCLUSION: The impact of
      ART in healthy women of advanced reproductive age in the years after delivery is
      not limited to the possible development of cardiovascular risk factors, such as
      hypertension, but can also influence the age of onset of menopause.

PMID- 27718321
TI  - Biliary diseases as main causes of pyogenic liver abscess caused by extended
      spectrum beta-lactamase-producing Enterobacteriaceae.
AB  - BACKGROUND & AIMS: Little is known about aetiology and morbidity and clinical
      characteristics of pyogenic liver abscess caused by extended-spectrum beta
      lactamase-producing Enterobacteriaceae. METHODS: An analysis between pyogenic
      liver abscess patients caused by extended-spectrum beta-lactamase-producing
      Enterobacteriaceae isolates and those caused by non-extended-spectrum beta
      lactamase-producing Enterobacteriaceae was performed. RESULTS: Among 817 pyogenic
      liver abscess patients, there were 176 patients (21.5%) with pyogenic liver
      abscess of biliary origin, and 67 pyogenic liver abscess patients (8.2%) caused
      by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates (mainly
      Escherichia coli and Klebsiella pneumoniae). Of 176 pyogenic liver abscess
      patients related to biliary disorders, there were 48 pyogenic liver abscess
      patients (27.3%) caused by extended-spectrum beta-lactamase-producing
      Enterobacteriaceae. Within 67 pyogenic liver abscess patients caused by
      Enterobacteriaceae expressing extended-spectrum beta-lactamases, the occurrences
      of 48 pyogenic liver abscess patients (71.6%) were associated with biliary
      disorders. When compared with pyogenic liver abscess patients caused by non
      extended-spectrum beta-lactamase-producing Enterobacteriaceae, there were
      significantly greater incidences of polymicrobial infections, bacteremia,
      pulmonary infection, recurrence and death in pyogenic liver abscess patients
      caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae.
      Carbapenems remain mainstay drugs against extended-spectrum beta-lactamase
      producing E. coli and K. pneumoniae. Independent risk factors for occurrence of
      pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing
      Enterobacteriaceae were biliary disorders including extra- and intrahepatic
      cholangiolithiasis and an abnormal bilioenteric communication between bile and
      gut, a treatment history of malignancy such as operation and chemotherapy,
      pulmonary infection, and diabetes mellitus. CONCLUSIONS: Pyogenic liver abscess
      caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates
      mainly occurs in patients with biliary disorders or with a treatment history of
      malignancy. The mainstay of treatment remains carbapenems in combination with
      adequate aspiration or drainage.

PMID- 27718322
TI  - Longitudinal mutational analysis of a cerebellar pilocytic astrocytoma recurring
      as a ganglioglioma.
AB  - A cerebellar pilocytic astrocytoma (PA) in a child recurred first with a PA
      histology and then with features of a ganglioglioma (GG). Molecular genetic
      analyses of the tumors confirmed a BRAF V600E mutation in all. They also all
      harbored a T202M mutation in ERK1, a kinase downstream of BRAF that is implicated
      in glial versus neuronal differentiation. The GG sample contained several
      variants that were not present in the PA samples; in particular, it had a
      truncating mutation in MAP2. These findings not only underscore the role of BRAF
      as oncogenic driver but also suggest that other genes may influence tumor
      morphology.

PMID- 27718323
TI  - Heritable cancer: Rounding up the not so usual suspects.

PMID- 27718324
TI  - Childhood-onset autoimmune cytopenia as the presenting feature of biallelic ACP5
      mutations.
AB  - Childhood-onset chronic and refractory cytopenias are rare and may be genetic in
      etiology. We report three pediatric cases of severe autoimmune thrombocytopenia
      or anemia associated with growth retardation and spastic diplegia with
      intracranial calcification. The identification of platyspondyly and metaphyseal
      lesions suggested a potential diagnosis of spondyloenchondrodysplasia (SPENCD),
      which was confirmed with the identification of biallelic ACP5 mutations. Two
      patients demonstrated elevated serum interferon alpha levels. Our report
      highlights ACP5-associated disease as a cause of childhood-onset autoimmune
      cytopenia, particularly combined with growth retardation and/or spasticity.
      Furthermore, a role for type I interferon in the pathogenesis of autoimmune
      cytopenias is supported.

PMID- 27718325
TI  - First Report on Rare Unifloral Honey of Endemic Moltkia petraea (Tratt.) Griseb.
      from Croatia: Detailed Chemical Screening and Antioxidant Capacity.
AB  - Rare Moltkia petraea (Tratt.) Griseb. honey from Croatia was first time
      characterised. The spectrophotometric assays on CIE L*a*b*Cab *hab  degrees 
      colour coordinates, total phenol content and antioxidant capacity (FRAP, CUPRAC,
      DPPH* and ABTS*+ assays) determined higher honey values generally close to dark
      honeys ranges. Headspace solid-phase microextraction (HS-SPME) on two fibres
      after GC-FID and GC/MS revealed the major compounds 2-phenylacetaldehyde (12.8%;
      15.6%), benzaldehyde (11.1%; 10.0%), octane (9.3%; 7.6%), nonane, propan-2-one,
      pentan-2-one, pentanal and nonanal (4.9%; 14.5%). Ultrasonic solvent extraction
      (USE) mainly isolated non-specific higher molecular compounds characteristic of
      the comb environment. Targeted HLPC-DAD analysis of the honey determined higher
      concentration of phenylalanine (212.08 mg/kg) and lumichrome (16.25 mg/kg) along
      with tyrosine and kojic acid. The headspace composition (chemical fingerprint)
      and high concentration of lumichrome can be considered particular for M. petraea
      honey.

PMID- 27718326
TI  - Potential use of metabolic breath tests to assess liver disease and prognosis:
      has the time arrived for routine use in the clinic?
AB  - The progression of liver disease may be unique among organ system diseases in
      that progressive fibrosis compromises not only the sufficiency of hepatocyte mass
      but also impairs blood flow to the liver, resulting in porto-systemic shunting.
      Although liver biopsy as an assessment of fibrosis has become the key biomarker
      of and target for new therapies, it is invasive and subject to sampling error,
      and cannot quantify metabolic function or porto-systemic shunting. Measurement of
      the hepatic venous pressure gradient accommodates some of the deficiencies of
      biopsy but requires expertise not widely available and misses minor changes in
      hepatocellular mass and thereby information about metabolic function. Thus, an
      unmet need in clinical hepatology remains unfulfilled: a noninvasive biomarker
      which quantitates both the hepatocellular insufficiency and porto-systemic
      shunting inherent in progressive hepatic fibrosis. Ideally, such a biomarker
      should correlate with clinical endpoints including liver-related survival and
      cirrhotic complications, be performed at the point-of-care, and be affordable and
      easy to use. This review, an expert opinion, summarizes background and recent
      data suggesting that metabolic breath tests may now meet these requirements and
      have a valid place in clinical hepatology to supplant the time-honoured
      assessment of hepatic fibrosis.

PMID- 27718328
TI  - RNA-Seq identifies redox balance related gene expression alterations under acute
      cadmium exposure in yeast.
AB  - The nonessential metal cadmium can cause cell toxicity and is associated with a
      range of human diseases including cardiovascular diseases, neurodegenerative
      diseases and cancers. In this study, cadmium-induced global gene expression
      profile of yeast was obtained using RNA Sequencing (RNA-Seq) and further analyzed
      by means of informatics and experiments. A total of 912 Differentially Expressed
      Genes (DEGs) (FDR of q < 0.01), including 415 Cd-inducible and 497 Cd-repressed
      genes were identified. Based on the DEGs, 25 cadmium responsive Clusters of
      Orthologous Group (COG) and three types of cadmium-induced Gene Ontology (GO)
      including cellular components, molecular functions and biological processes were
      analyzed in details. Thereafter, 79 Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathways under cadmium exposure were assigned. Collectively, 108 redox
      balance related genes were extracted under cadmium exposure. Meanwhile, cadmium
      exposure lowered cellular Mitochondrial Membrane Potential (MMP) and increased
      Reactive Oxygen Species (ROS) levels significantly in the context of
      mitochondrial dysfunction. Furthermore, cadmium exposure increased cellular GSH
      levels and decreased GSSG levels and also lowered GSSG/GSH ratio of cells, which
      supports experimentally our claim that the redox balance is the primary mechanism
      for cadmium toxicity. The results present in this study may provide new
      strategies for cadmium detoxification and prevention or therapies of cadmium
      associated diseases.

PMID- 27718327
TI  - The newborn human NK cell repertoire is phenotypically formed but functionally
      reduced.
AB  - BACKGROUND: Infection is a leading cause of death worldwide in babies under 1
      month of age. Better vaccines and therapeutics are desperately needed for this
      vulnerable population. METHODS: Because newborns rely heavily on the innate
      immune system, we evaluated cell phenotype and function of some of the earliest
      cellular responders during infection, natural killer (NK) cells. We used mass
      cytometry to provide a comprehensive comparison of NK cells from umbilical cord
      blood and adult peripheral blood. RESULTS: In unsupervised analyses, including
      viSNE and principal component analysis, the structure of the cord blood and adult
      NK cell repertoires are highly similar, distinguishable mainly by maturity
      related markers expressed on rare subpopulations of cells. However, in functional
      analyses, cord blood NK cells show reduced degranulation and cytokine production
      following target recognition, as well as antibody-dependent cell-mediated
      cytotoxicity and apoptosis induction in targets. CONCLUSIONS: These findings show
      that the structure of the NK cell repertoire is intact at birth, suggesting great
      potential for vaccine and therapeutic strategies targeting this cell population.
      (c) 2016 International Clinical Cytometry Society.

PMID- 27718329
TI  - Combined use of Bacillus subtilis strain B-001 and bactericide for the control of
      tomato bacterial wilt.
AB  - BACKGROUND: Tomato bacterial wilt caused by Ralstonia solanacearum poses a
      serious threat to tomato production. However, no effective control measures are
      available. In this study, the bactericide Saisentong was combined with an
      effective biological control agent, Bacillus subtilis B-001, to control tomato
      bacterial wilt under greenhouse and field conditions. RESULTS: Growth of B-001 in
      vitro was unaffected by Saisentong. In greenhouse experiments, the combined
      application of B-001 and Saisentong via root irrigation or spray resulted in
      better disease control compared with either agent alone. In two field trials, at
      a Saisentong concentration of 400 or 500 mg kg-1 , the combined treatment was
      more effective than expected and showed a synergistic effect. A lower
      concentration of Saisentong (200 or 300 mg kg-1 ) in combination with B-001
      resulted in an antagonistic effect. However, disease control was significantly
      greater compared with either treatment alone. CONCLUSION: The combination of
      Saisentong and B-001 effectively controls tomato bacterial wilt. The integrated
      strategy represents a promising new tool to control this disease. (c) 2016
      Society of Chemical Industry.

PMID- 27718331
TI  - Ovarian clear cell carcinoma with plasma cell-rich inflammatory stroma:
      Cytological Findings of a Case.
AB  - We report a case of clear cell carcinoma (CCC) of the ovary with plasma cell-rich
      inflammatory stroma, a recently proposed subtype of CCC, and present the
      cytological findings. The patient was a 48-year-old woman, who was incidentally
      found to have a right ovarian tumor during the preoperative work-up for an early
      stage adenocarcinoma of the uterine cervix. Cytological examination of an imprint
      smear of the ovarian tumor and peritoneal washing revealed solid cell clusters of
      irregular, often dendritic shapes, which were intermingled with many inflammatory
      cells. "Raspberry bodies" were not found. Histopathological examination of the
      extirpated ovarian tumor showed the features of CCC with plasma cell-rich
      inflammatory stroma. This subtype of ovarian CCC poses cytological and
      histological diagnostic problems, and its differentiation from dysgerminoma is
      often difficult, because it mostly lacks the hyaline or mucoid stroma.
      Irregularly shaped clusters of large polyhedral cells, coarsely clumped nuclear
      chromatin, and plasma cell-rich inflammatory infiltrates suggest CCC, but the
      cytological differences between dysgerminoma and CCC are often subtle, and
      immunohistochemical examinations for cytokeratin 7 or epithelial membrane antigen
      may be necessary. Diagn. Cytopathol. 2017;45:128-132. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27718330
TI  - Risk Profile of Hepatitis E Virus from Pigs or Pork in Canada.
AB  - The role and importance of pigs and pork as sources of zoonotic hepatitis E virus
      (HEV) has been debated in Canada and abroad for over 20 years. To further
      investigate this question, we compiled data to populate a risk profile for HEV in
      pigs or pork in Canada. We organized the risk profile (RP) using the headings
      prescribed for a foodborne microbial risk assessment and used research synthesis
      methods and inputs wherever possible in populating the fields of this RP. A
      scoping review of potential public health risks of HEV, and two Canadian field
      surveys sampling finisher pigs, and retail pork chops and pork livers, provided
      inputs to inform this RP. We calculated summary estimates of prevalence using the
      Comprehensive Meta-analysis 3 software, employing the method of moments. Overall,
      we found the incidence of sporadic locally acquired hepatitis E in Canada,
      compiled from peer-reviewed literature or from diagnosis at the National
      Microbiology Laboratory to be low relative to other non-endemic countries. In
      contrast, we found the prevalence of detection of HEV RNA in pigs and retail pork
      livers, to be comparable to that reported in the USA and Europe. We drafted risk
      categories (high/medium/low) for acquiring clinical hepatitis E from exposure to
      pigs or pork in Canada and hypothesize that the proportion of the Canadian
      population at high risk from either exposure is relatively small.

PMID- 27718332
TI  - Plant community, geographic distance and abiotic factors play different roles in
      predicting AMF biogeography at the regional scale in northern China.
AB  - Arbuscular mycorrhizal fungi (AMF) are ubiquitous mutualists of terrestrial
      plants and play key roles in regulating various ecosystem processes, but little
      is known about AMF biogeography at regional scale. This study aims at exploring
      the key predictors of AMF communities across a 5000-km transect in northern
      China. We determined the soil AMF species richness and community composition at
      47 sites representative of four vegetation types (meadow steppe, typical steppe,
      desert steppe and desert) and related them to plant community characteristics,
      abiotic factors and geographic distance. The results showed that soil pH was the
      strongest predictor of AMF richness and phylogenetic diversity. However, abiotic
      factors only have a low predictive effect on AMF community composition or
      phylogenetic patterns. By contrast, we found a significant relationship between
      community composition of AMF and plants, which was a surprising result given the
      extent of heterogeneity in the plant community across this transect. Moreover,
      the geographic distance predominantly explained the AMF phylogenetic structure,
      implying that history evolutionary may play a role in shaping AMF biogeographic
      patterns. This study highlighted the different roles of main factors in
      predicting AMF biogeography, and bridge landscape-scale studies to more recent
      global-scale efforts.

PMID- 27718333
TI  - Fine needle aspiration in intraocular metastasis from pleuropulmonary blastoma. A
      case report and a review of the literature.
AB  - Pleuropulmonary blastoma (PPB) is a rare primitive intrathoracic malignant
      neoplasm that occurs almost exclusively in children and adolescents. PPB is
      classified into three types according to the presence of cystic and solid areas.
      We report a case of PPB with an intraocular metastasis diagnosed by fine needle
      aspiration (FNA): 3-year-old female was treated for type II PPB by neoadjuvant
      chemotherapy and surgery. Four years later, she presented with an intraocular
      lesion. To differentiate between metastasis or other malignancy, a transcleral
      FNA was performed and showed two cellular populations represented by roundish
      malignant cells and spindle-shaped cells. The patient was treated with
      chemotherapy and diode laser ablation. A year later, the patient had enucleation
      and rare residual cells were found on the histological specimen. Patient remains
      disease-free 66 months after the last surgical treatment. Diagn. Cytopathol.
      2017;45:156-160. (c) 2016 Wiley Periodicals, Inc.

PMID- 27718334
TI  - Getting at the "what" and the "how" in symbiosis.
AB  - Symbioses are ubiquitous and have had a tremendous impact on the evolution of
      life on the planet. Indeed, endosymbiosis lead to the generation of the first
      eukaryotic cell and from that point onwards, eukaryotes have interacted with the
      other domains of life, sometimes forming persistent and necessary relationships
      that span generations. However, because the majority of hosts and symbionts are
      not easily manipulated, the intricate details of these symbioses, an
      understanding of the molecular underpinnings of these interactions, have not been
      elucidated. It is difficult to ask questions about the details of a host-microbe
      symbiosis if either member cannot be cultured, genetically manipulated, or even
      housed in a laboratory. Several technological advances in recent years may
      address these difficulties, making it easier for researchers to ask mechanistic
      questions in symbiotic systems.

PMID- 27718335
TI  - PSMC (pairwise sequentially Markovian coalescent) analysis of RAD (restriction
      site associated DNA) sequencing data.
AB  - The pairwise sequentially Markovian coalescent (PSMC) method uses the genome
      sequence of a single individual to estimate demographic history covering a time
      span of thousands of generations. Although originally designed for whole-genome
      data, we here use simulations to investigate its applicability to reference
      genome-aligned restriction site associated DNA (RAD) data. We find that RAD data
      can potentially be used for PSMC analysis, but at present with limitations. The
      key factor is the proportion (p) of the genome that the RAD data covers. In our
      simulations, a proportion of 10% can still retain a substantial amount of
      coalescent information, whereas for 1% estimation becomes unreliable. The
      performance depends strongly on mutation rate (MU) and recombination rate (r) and
      is proportional to MU*p/r. When the value of this term is low, increasing the
      amount of data and number of iterations helps restoring the power of the
      estimation. We subsequently analyse one whole-genome-sequenced and 17 RAD
      sequenced three-spined sticklebacks (Gasterosteus aculeatus) from a lake in
      Greenland. The whole-genome sequence suggests a relatively recent expansion and
      decline within ca. 4000-40 000 generations ago, possibly reflecting postglacial
      expansion and founding of the lake population. RAD data, where chromosomes from
      10 individuals are combined, identify a similar pattern. Our study provides
      guidance about the use of PSMC analysis and suggests measures that can improve
      its utility for RAD data. Finally, the study shows that RAD loci in general
      contain coalescent information that can be used for developing more targeted
      methods.

PMID- 27718336
TI  - Characterization of Foot-and-Mouth Disease Viruses Collected in Nigeria Between
      2007 and 2014: Evidence for Epidemiological Links Between West and East Africa.
AB  - This study describes the molecular characterization of 47 foot-and-mouth disease
      (FMD) viruses recovered from field outbreaks in Nigeria between 2007 and 2014.
      Antigen ELISA of viral isolates was used to identify FMD virus serotypes O, A and
      SAT 2. Phylogenetic analyses of VP1 nucleotide sequences provide evidence for the
      presence of multiple sublineages of serotype SAT 2, and O/EAST AFRICA 3 (EA-3)
      and O/WEST AFRICA topotypes in the country. In contrast, for serotype A, a single
      monophyletic cluster of viruses has persisted within Nigeria (2009-2013). These
      results demonstrate the close genetic relatedness of viruses in Nigeria to those
      from other African countries, including the first formal characterization of
      serotype O/EA-3 viruses in Nigeria. The introductions and persistence of certain
      viral lineages in Nigeria may reflect transmission patterns via nomadic
      pastoralism and animal trade. Continuous monitoring of field outbreaks is
      necessary to dissect the complexity of FMD epidemiology in sub-Saharan Africa.

PMID- 27718338
TI  - Opossum peptide that can neutralize rattlesnake venom is expressed in Escherichia
      coli.
AB  - An eleven amino acid ribosomal peptide was shown to completely neutralize Western
      Diamondback Rattlesnake (Crotalus atrox) venom in mice when a lethal dose of the
      venom was pre-incubated with the peptide prior to intravenous injection. We have
      expressed the peptide as a concatenated chain of peptides and cleaved them apart
      from an immobilized metal affinity column using a protease. After ultrafiltration
      steps, the mixture was shown to partially neutralize rattlesnake venom in mice.
      Preliminary experiments are described here that suggest a potential life-saving
      therapy could be developed. To date, no recombinant therapies targeting cytotoxic
      envenomation have been reported. (c) 2016 American Institute of Chemical
      Engineers Biotechnol. Prog., 33:81-86, 2017.

PMID- 27718337
TI  - Different Lineage of Porcine Deltacoronavirus in Thailand, Vietnam and Lao PDR in
      2015.
AB  - Porcine deltacoronavirus (PDCoV) was detected by RT-PCR in 12 of 97 (12.4%)
      intestinal samples collected during 2015 from piglets with diarrhoea in Thailand,
      Vietnam and Lao PDR. Spike, membrane and nucleocapsid genes were characterized,
      and phylogenetic analyses demonstrated that PDCoV isolates from Thai and Lao PDR
      form a novel cluster, separated from US and China isolates, but relatively were
      more closely related to China PDCoV than US isolates. Vietnam PDCoVs, however,
      were grouped together with US PDCoV. The analyses of amino acid changes suggested
      that they were from different lineage.

PMID- 27718340
TI  - A trend toward smaller optical angles and medial-ocular distance in schizophrenia
      spectrum, but not in bipolar and major depressive disorders.
AB  - Minor physical anomalies (MPAs) are subtle signs of fetal developmental
      abnormalities that have been considered to be among the most replicated risk
      markers for schizophrenia-spectrum disorders. However, quantitative approaches
      are needed to measure craniofacial MPAs. The present study adopted an imaging
      based quantitative approach to examine craniofacial MPAs across the spectrum of
      schizophrenia and affective disorders, to address their sensitivity and
      specificity. We sampled 31 patients with schizophrenia, 30 of their unaffected
      relatives, and 30 individuals with schizotypal personality traits, as well as 37
      non-schizotypal controls. We also examined 17 patients with bipolar disorder and
      19 patients with major depressive disorder. Five craniofacial MPAs were measured
      on anterior-posterior commissure-aligned T1-weighted images of an individual's
      native brain space: medial-ocular distance, lateral-ocular distance, optical
      angle, maximum skull length, and skull-base width. Compared to non-schizotypal
      controls, patients with schizophrenia and their relatives showed a trend toward
      having smaller optical angles and medial-ocular distance, while no difference was
      found in patients with bipolar or major depressive disorders, suggesting some
      degree of specificity to schizophrenia. Our approach may benefit future research
      on craniofacial MPAs as risk markers for schizophrenia-spectrum disorders, and
      may eventually be useful in strategies to enhance risk stratification using
      multiple risk markers.

PMID- 27718339
TI  - Recent advances in immobilization strategies for glycosidases.
AB  - Glycans play important biological roles in cell-to-cell interactions, protection
      against pathogens, as well as in proper protein folding and stability, and are
      thus interesting targets for scientists. Although their mechanisms of action have
      been widely investigated and hypothesized, their biological functions are not
      well understood due to the lack of deglycosylation methods for large-scale
      isolation of these compounds. Isolation of glycans in their native state is
      crucial for the investigation of their biological functions. However, current
      enzymatic and chemical deglycosylation techniques require harsh pretreatment and
      reaction conditions (high temperature and use of detergents) that hinder the
      isolation of native glycan structures. Indeed, the recent isolation of new
      endoglycosidases that are able to cleave a wider variety of linkages and
      efficiently hydrolyze native proteins has opened up the opportunity to elucidate
      the biological roles of a higher variety of glycans in their native state. As an
      example, our research group recently isolated a novel Endo-beta-N
      acetylglucosaminidase from Bifidobacterium longum subsp. infantis ATCC 15697
      (EndoBI-1) that cleaves N-N'-diacetyl chitobiose moieties found in the N-linked
      glycan (N-glycan) core of high mannose, hybrid, and complex N-glycans. This
      enzyme is also active on native proteins, which enables native glycan isolation,
      a key advantage when evaluating their biological activities. Efficient, stable,
      and economically viable enzymatic release of N-glycans requires the selection of
      appropriate immobilization strategies. In this review, we discuss the state-of
      the-art of various immobilization techniques (physical adsorption, covalent
      binding, aggregation, and entrapment) for glycosidases, as well as their
      potential substrates and matrices. (c) 2016 American Institute of Chemical
      Engineers Biotechnol. Prog., 33:104-112, 2017.

PMID- 27718342
TI  - Corrigendum.

PMID- 27718341
TI  - Developmental trajectory of time perspective: From children to older adults.
AB  - Time perspective is a fundamental dimension of the psychological time construct,
      with a pervasive and powerful influence on human behavior. However, the
      developmental trajectory of time perspective across a human lifespan remains
      unclear. The current study aimed to portray the developmental trajectory of all
      dimensions of time perspectives from children to older adults in a large sample.
      A total of 1,901 individuals (aged 9-84 years) completed measures of time
      perspective. They were then divided into five age groups: children, teenagers,
      young adults, middle-aged adults, and older adults. Results suggested that each
      time perspective showed a unique developmental pattern across the lifespan.
      Moreover, perceived economic situation and education were related to some
      dimensions of time perspective.

PMID- 27718344
TI  - Advances in Cardiac Biological Therapies 2016.

PMID- 27718343
TI  - Commercial Production of Autologous Stem Cells and Their Therapeutic Potential
      for Liver Cirrhosis.
AB  - Human adipose-derived stem cells (hADSCs) are a promising source of autologous
      stem cells for personalized cell-based therapies. Culture expansion of ADSCs
      provides an attractive opportunity for liver cirrhosis patients. However, safety
      and stability issues can pose big challenges for personalized autologous stem
      cell products. In the present study, we addressed whether the commercial
      production program could provide a consistent product for liver cirrhosis
      therapy. We collected adipose tissue from three human donors by lipoaspirate and
      isolated ADSCs, which were expanded in culture to reach 1 * 108 cells (an
      approximately 1,000-fold expansion) within four passages. We then examined their
      morphology, chromosome stability, surface markers, and differentiation ability
      after culture. Next, we explored their therapeutic potential using a rat model of
      thioacetamide-induced liver cirrhosis. Culture-expanded ADSCs were injected
      intrahepatically, and their biodistribution was tracked by immunohistochemistry
      using an antibody against human mitochondria. Finally, we tested for tumor
      development by subcutaneously injecting a 100-fold dose range of cultured ADSCs
      into immunocompromised mice. Taken together, we find that culture expansion of
      autologous ADSCs is a potentially suitable stem cell product for personalized
      cell-based therapy for patients with liver cirrhosis.

PMID- 27718345
TI  - Improving the Diagnostic Capabilities of Vestibular-Evoked Myogenic Potentials.

PMID- 27718346
TI  - Prevalence of Auditory Processing Disorder in School-Aged Children in the Mid
      Atlantic Region.
AB  - BACKGROUND: Although auditory processing disorder (APD) is a widely recognized
      impairment, its prevalence and demographic characteristics are not precisely
      known in the pediatric population. PURPOSE: To examine the demographic
      characteristics of children diagnosed with APD at a tertiary health-care facility
      and the prevalence of pediatric APD. RESEARCH DESIGN: A cross-sectional study.
      STUDY SAMPLE: A total of 243 children (149 boys and 94 girls) who were referred
      to the Nemours Audiology Clinics in the Delaware Valley for an APD evaluation.
      The mean ages were 9.8 yr for boys and 9.7 yr for girls. Out of 243 children
      referred for an APD evaluation, 94 children exhibited one or more auditory
      processing deficits in the areas of auditory closure, auditory figure ground,
      binaural integration, binaural separation, and temporal processing. DATA
      COLLECTION AND ANALYSIS: Demographic and audiological data, clinical history
      (parental reports on prenatal and postnatal information, birth weight and height,
      medical and developmental history, otologic/audiological history, education
      information, behavioral characteristics), and results of the APD test battery
      were retrospectively obtained from the electronic medical records of each
      participant. The prevalence of APD was estimated using the total number of
      students enrolled in the same school attended by each participant in the 2011
      academic year as cohort. RESULTS: The prevalence of APD was 1.94 per 1,000
      children in this study. We found that prevalence of APD among the children who
      attended private schools was more than two times higher than the children who
      attended public schools. The results also revealed that the majority of children
      referred to the clinics were Caucasian (85.6%), whereas minority groups were
      underrepresented for this geographical area with only 3.7% of Hispanic or Latino
      children and 5.8% of Black or African American children. CONCLUSIONS: The
      estimated prevalence of APD in the current study was lower than the previously
      published estimates. The difference might be due to the diagnosis criteria of APD
      among studies as well as the use of school enrollment number as the referenced
      population to estimate prevalence in our study. We also found a significant
      difference in APD prevalence depending on the school types. The findings of
      higher prevalence rates among the children attending private schools and higher
      proportion of Caucasians children referred for APD evaluation suggest that more
      children among those in public schools and in the Hispanic and African American
      groups should have been referred for an APD evaluation. Hence, the current
      estimate is likely an underestimate of the actual APD prevalence. The low
      percentage of Hispanic or African American children referred to the clinic for
      APD evaluations may be related to the socioeconomic status and linguistic
      differences among the concerned families. The results of this study raise the
      importance of adapting the APD test battery for children with a different
      linguistic background as well as increasing awareness of available clinical
      resources to all families in our area.

PMID- 27718347
TI  - Behavioral Measures of Temporal Processing and Speech Perception in Cochlear
      Implant Users.
AB  - BACKGROUND: Although most cochlear implant (CI) users achieve improvements in
      speech perception, there is still a wide variability in speech perception
      outcomes. There is a growing body of literature that supports the relationship
      between individual differences in temporal processing and speech perception
      performance in CI users. Previous psychophysical studies have emphasized the
      importance of temporal acuity for overall speech perception performance.
      Measurement of gap detection thresholds (GDTs) is the most common measure
      currently used to assess temporal resolution. However, most GDT studies completed
      with CI participants used direct electrical stimulation not acoustic stimulation
      and they used psychoacoustic research paradigms that are not easy to administer
      clinically. Therefore, it is necessary to determine if the variance in GDTs
      assessed with clinical measures of temporal processing such as the Randomized Gap
      Detection Test (RGDT) can be used to explain the variability in speech perception
      performance. PURPOSE: The primary goal of this study was to investigate the
      relationship between temporal processing and speech perception performance in CI
      users. RESEARCH DESIGN: A correlational study investigating the relationship
      between behavioral GDTs (assessed with the RGDT or the Expanded Randomized Gap
      Detection Test) and commonly used speech perception measures (assessed with the
      Speech Recognition Test [SRT], Central Institute for the Deaf W-22 Word
      Recognition Test [W-22], Consonant-Nucleus-Consonant Test [CNC], Arizona
      Biomedical Sentence Recognition Test [AzBio], Bamford-Kowal-Bench Speech-in-Noise
      Test [BKB-SIN]). STUDY SAMPLE: Twelve postlingually deafened adult CI users (24
      83 yr) and ten normal-hearing (NH; 22-30 yr) adults participated in the study.
      DATA COLLECTION AND ANALYSIS: The data were collected in a sound-attenuated test
      booth. After measuring pure-tone thresholds, GDTs and speech perception
      performance were measured. The difference in performance between-participant
      groups on the aforementioned tests, as well as the correlation between GDTs and
      speech perception performance was examined. The correlations between
      participants' biologic factors, performance on the RGDT and speech perception
      measures were also explored. RESULTS: Although some CI participants performed as
      well as the NH listeners, the majority of the CI participants displayed temporal
      processing impairments (GDTs > 20 msec) and poorer speech perception performance
      than NH participants. A statistically significant difference was found between
      the NH and CI test groups in GDTs and some speech tests (SRT, W-22, and BKB-SIN).
      For the CI group, there were significant correlations between GDTs and some
      measures of speech perception (CNC Phoneme, AzBio, BKB-SIN); however, no
      significant correlations were found between biographic factors and GDTs or speech
      perception performance. CONCLUSIONS: Results support the theory that the
      variability in temporal acuity in CI users contributes to the variability in
      speech performance. Results also indicate that it is reasonable to use the
      clinically available RGDT to identify CI users with temporal processing
      impairments for further appropriate rehabilitation.

PMID- 27718348
TI  - Brain Positron Emission Tomography-Computed Tomography Gender Differences in
      Tinnitus Patients.
AB  - BACKGROUND: Increased metabolism in the left auditory cortex has been reported in
      tinnitus patients. However, gender difference has not been addressed. PURPOSE: To
      assess the differences in Positron emission tomography-computed tomography (PET
      CT) results between the genders in tinnitus patients. RESEARCH DESIGN:
      Retrospective cohort. STUDY SAMPLE: Included were patients referred to our clinic
      between January 2011 and August 2013 who complained of tinnitus and underwent
      fluorodeoxyglucose (FDG)-PET to assess brain metabolism. DATA ANALYSIS:
      Univariate and multivariate nominal logistic regressions were used to evaluate
      the association between upper temporal gyrus (UTG; right and left) and gender.
      RESULTS: Included were 140 patients (87 males) with an average age of 52.5 yr
      (median = 53.1). Bilateral tinnitus was found in 85 patients (60.7%), left sided
      in 30 (21.4%), and right sided in 21(15%). Increased uptake in the UTG was found
      in 60% of the patients on either side. Males had a statistically significant
      increased uptake in the UTG in those with unilateral tinnitus and in the entire
      population. CONCLUSIONS: We present the largest study reported so far on tinnitus
      patients who have undergone FDG-PET-CT. We found a statistically significant
      difference between the genders in FDG uptake by the UTG. Further investigations
      should be undertaken to reveal the etiologies for these differences and to assess
      different therapeutic protocols according to gender.

PMID- 27718349
TI  - Validation of a Mobile Device for Acoustic Coordinated Reset Neuromodulation
      Tinnitus Therapy.
AB  - BACKGROUND: Sound-based tinnitus intervention stimuli include broad-band noise
      signals with subjectively adjusted bandwidths used as maskers delivered by
      commercial devices or hearing aids, environmental sounds broadly described and
      delivered by both consumer devices and hearing aids, music recordings
      specifically modified and delivered in a variety of different ways, and other
      stimuli. Acoustic coordinated reset neuromodulation therapy for tinnitus
      reduction has unique and more stringent requirements compared to all other sound
      based tinnitus interventions. These include precise characterization of tinnitus
      pitch and loudness, and effective provision of patient-controlled daily therapy
      signals at defined frequencies, levels, and durations outside of the clinic.
      PURPOSE: The purpose of this study was to evaluate an approach to accommodate
      these requirements including evaluation of a mobile device, validation of an
      automated tinnitus pitch-matching algorithm and assessment of a patient's ability
      to control stimuli and collect repeated outcome measures. RESEARCH DESIGN: The
      experimental design involved direct laboratory measurements of the sound delivery
      capabilities of a mobile device, comparison of an automated, adaptive pitch
      matching method to a traditional manual method and measures of a patient's
      ability to understand and manipulate a mobile device graphic user interface to
      both deliver the therapy signals and collect the outcome measures. STUDY SAMPLE:
      This study consisted of 5 samples of a common mobile device for the laboratory
      measures and a total of 30 adult participants: 15 randomly selected normal
      hearing participants with simulated tinnitus for validation of a tinnitus pitch
      matching algorithm and 15 sequentially selected patients already undergoing
      tinnitus therapy for evaluation of patient usability. INTERVENTION: No tinnitus
      intervention(s) were specifically studied as a component of this study. DATA
      COLLECTION AND ANALYSIS: Data collection involved laboratory measures of mobile
      devices, comparison of manual and automated adaptive tinnitus pitch-matching
      psychoacoustic procedures in the same participant analyzed for absolute
      differences (t test), variance differences (f test), and range comparisons, and
      assessment of patient usability including questionnaire measures and logs of
      patient observations. RESULTS: Mobile devices are able to reliably and accurately
      deliver the acoustic therapy signals. There was no difference in mean pitch
      matches (t test, p > 0.05) between an automated adaptive method compared to a
      traditional manual pitch-matching method. However, the variability of the
      automated pitch-matching method was much less (f test, p < 0.05) with twice as
      many matches within the predefined error range (+/-5%) compared to the manual
      pitch-matching method (80% versus 40%). After a short initial training, all
      participants were able to use the mobile device effectively and to perform the
      required tasks without further professional assistance.

PMID- 27718350
TI  - Smartphone-Based System for Learning and Inferring Hearing Aid Settings.
AB  - BACKGROUND: Previous research has shown that hearing aid wearers can successfully
      self-train their instruments' gain-frequency response and compression parameters
      in everyday situations. Combining hearing aids with a smartphone introduces
      additional computing power, memory, and a graphical user interface that may
      enable greater setting personalization. To explore the benefits of self-training
      with a smartphone-based hearing system, a parameter space was chosen with four
      possible combinations of microphone mode (omnidirectional and directional) and
      noise reduction state (active and off). The baseline for comparison was the
      "untrained system," that is, the manufacturer's algorithm for automatically
      selecting microphone mode and noise reduction state based on acoustic
      environment. The "trained system" first learned each individual's preferences,
      self-entered via a smartphone in real-world situations, to build a trained model.
      The system then predicted the optimal setting (among available choices) using an
      inference engine, which considered the trained model and current context (e.g.,
      sound environment, location, and time). PURPOSE: To develop a smartphone-based
      prototype hearing system that can be trained to learn preferred user settings.
      Determine whether user study participants showed a preference for trained over
      untrained system settings. RESEARCH DESIGN: An experimental within-participants
      study. Participants used a prototype hearing system-comprising two hearing aids,
      Android smartphone, and body-worn gateway device-for ~6 weeks. STUDY SAMPLE:
      Sixteen adults with mild-to-moderate sensorineural hearing loss (HL) (ten males,
      six females; mean age = 55.5 yr). Fifteen had >=6 mo of experience wearing
      hearing aids, and 14 had previous experience using smartphones. INTERVENTION:
      Participants were fitted and instructed to perform daily comparisons of settings
      ("listening evaluations") through a smartphone-based software application called
      Hearing Aid Learning and Inference Controller (HALIC). In the four-week-long
      training phase, HALIC recorded individual listening preferences along with sensor
      data from the smartphone-including environmental sound classification, sound
      level, and location-to build trained models. In the subsequent two-week-long
      validation phase, participants performed blinded listening evaluations comparing
      settings predicted by the trained system ("trained settings") to those suggested
      by the hearing aids' untrained system ("untrained settings"). DATA COLLECTION AND
      ANALYSIS: We analyzed data collected on the smartphone and hearing aids during
      the study. We also obtained audiometric and demographic information. RESULTS:
      Overall, the 15 participants with valid data significantly preferred trained
      settings to untrained settings (paired-samples t test). Seven participants had a
      significant preference for trained settings, while one had a significant
      preference for untrained settings (binomial test). The remaining seven
      participants had nonsignificant preferences. Pooling data across participants,
      the proportion of times that each setting was chosen in a given environmental
      sound class was on average very similar. However, breaking down the data by
      participant revealed strong and idiosyncratic individual preferences. Fourteen
      participants reported positive feelings of clarity, competence, and mastery when
      training via HALIC. CONCLUSIONS: The obtained data, as well as subjective
      participant feedback, indicate that smartphones could become viable tools to
      train hearing aids. Individuals who are tech savvy and have milder HL seem well
      suited to take advantages of the benefits offered by training with a smartphone.

PMID- 27718351
TI  - An Estimation of the Whole-of-Life Noise Exposure of Adolescent and Young Adult
      Australians with Hearing Impairment.
AB  - BACKGROUND: Since amplified music gained widespread popularity, there has been
      community concern that leisure-noise exposure may cause hearing loss in
      adolescents and young adults who would otherwise be free from hearing impairment.
      Repeated exposure to personal stereo players and music events (e.g.,
      nightclubbing, rock concerts, and music festivals) are of particular concern. The
      same attention has not been paid to leisure-noise exposure risks for young people
      with hearing impairment (either present from birth or acquired before adulthood).
      This article reports on the analysis of a subset of data (leisure participation
      measures) collected during a large, two-phase study of the hearing health,
      attitudes, and behaviors of 11- to 35-yr-old Australians conducted by the
      National Acoustic Laboratories (n = 1,667 hearing threshold level datasets
      analyzed). The overall aim of the two-phase study was to determine whether a
      relationship between leisure-noise exposure and hearing loss exists. PURPOSE: In
      the current study, the leisure activity profiles and accumulated ("whole-of
      life") noise exposures of young people with (1) hearing impairment and (2) with
      normal hearing were compared. RESEARCH DESIGN: Cross-sectional cohort study.
      STUDY SAMPLE: Hearing impaired (HI) group, n = 125; normal (nonimpaired) hearing
      (NH) group, n = 296, analyzed in two age-based subsets: adolescents (13- to 17-yr
      olds) and young adults (18- to 24-yr-olds). DATA COLLECTION AND ANALYSIS:
      Participant survey. The chi2 test was used to identify systematic differences
      between the leisure profiles and exposure estimates of the HI and NH groups.
      Whole-of-life noise exposure was estimated by adapting techniques described in
      ISO 1999. RESULTS: For adolescents, leisure profiles were similar for the two
      groups and few individuals exceeded the stated risk criterion. For young adults,
      participation was significantly lower for the HI group for 7 out of 18 leisure
      activities surveyed. Activity diversity and whole-of-life exposure were also
      significantly lower for the HI group young adults. A substantial number of
      individuals in both groups reported participation in leisure activities known to
      involve high noise levels (HI < NH). The individual whole-of-life exposures for
      the HI and NH participants were estimated and group median exposures were
      calculated. The median exposure for HI group young adults was significantly lower
      than that for the NH group (710 versus 1,615 Pa2 h [Pascal squared hours]).
      CONCLUSIONS: The number of young adults with estimated exposure above the chosen
      noise-risk criterion in the NH group is concerning. With respect to the goals of
      hearing loss prevention initiatives, the more conservative social behavior (e.g.,
      less nightclubbing) observed among HI group young adults may be regarded as a
      positive finding, but it could also signify relative social disadvantage for some
      young adults with hearing impairment.

PMID- 27718353
TI  - A Response Letter to the McCreery et al (2016) Article "Stability of Audiometric
      Thresholds for Children with Hearing Aids Applying the American Academy of
      Audiology Pediatric Amplification Guideline: Implications for Safety".

PMID- 27718352
TI  - Utility of the Frequency Tuning Measure of oVEMP in Differentiating Meniere's
      Disease from BPPV.
AB  - BACKGROUND: Utility of frequency tuning of ocular vestibular evoked myogenic
      potential (oVEMP) for evaluation of utricular function in individuals with
      Meniere's disease is a recent development. However, there is dearth of studies
      regarding its utility in differential diagnosis of Meniere's disease from other
      vestibular pathologies. PURPOSE: The present study aimed at investigating the
      feasibility of frequency tuning of oVEMP in discriminating Meniere's disease from
      benign paroxysmal positional vertigo (BPPV). RESEARCH DESIGN: Static group
      comparison. STUDY SAMPLE: oVEMPs were acquired from 36 individuals, each with
      unilateral Meniere's disease and unilateral BPPV. Thirty-six age- and gender
      matched healthy individuals formed comparison group for each of the two clinical
      groups. INTERVENTION: Contralateral oVEMPs were recorded from both ears of all
      the participants. DATA COLLECTION AND ANALYSES: The responses pertaining to
      octave and mid-octave frequencies from 250 to 4000 Hz, one frequency presented at
      a time, were recorded from infra-orbital electrodes (noninverting placed 1 cm
      below the lower eyelid and inverting 2 cm below the inverting on the cheek) with
      forehead as ground. Starting intensity was 125 dB peSPL with subsequent
      reductions in 10-dB steps to arrive at threshold. The stimuli were delivered to
      the ear at a rate of 5.1 Hz. The frequency corresponding to the largest peak-to
      peak amplitude, best threshold, and/or largest peak-to-peak amplitude at
      thresholds was considered as the tuning frequency. Proportions of ears with
      frequency tuning at a particular frequency were compared between the groups.
      RESULTS: The frequency tuning at 1000 Hz was found to exist in a significantly
      higher proportion of affected ears with Meniere's disease than the comparison
      group as well as ears with BPPV (p < 0.05). Using a criterion point of frequency
      tuning at 875 Hz, the sensitivity and specificity for identifying Meniere's
      disease was found to be 68% and 100%, respectively. CONCLUSION: The shift in
      frequency tuning is an efficient parameter for not only discriminating Meniere's
      disease from healthy individuals but also distinguishing it from BPPV. Therefore,
      frequency tuning is recommended as a test parameter of oVEMP for identification
      of Meniere's disease.

PMID- 27718354
TI  - Response to Johnson.

PMID- 27718358
TI  - E. coli metabolic engineering for gram scale production of a plant-based anti
      inflammatory agent.
AB  - In this report, the heterologous production of salicylate (SA) is the basis for
      metabolic extension to salicylate 2-O-beta-d-glucoside (SAG), a natural product
      implicated in plant-based defense mechanisms. Production was optimized through a
      combination of metabolic engineering, gene expression variation, and co-culture
      design. When combined, SA and SAG production titers reached ~0.9g/L and ~2.5g/L,
      respectively. The SAG compound was then tested for anti-inflammatory properties
      relative to SA and acetylsalicylate (aspirin). Results indicate comparable
      activity between SAG and aspirin in reducing nitric oxide (NO) and reactive
      oxygen species (ROS) from macrophage cells while no discernable negative effects
      on cellular viability were observed.

PMID- 27718357
TI  - Ankyrin-B is a PI3P effector that promotes polarized alpha5beta1-integrin
      recycling via recruiting RabGAP1L to early endosomes.
AB  - Endosomal membrane trafficking requires coordination between phosphoinositide
      lipids, Rab GTPases, and microtubule-based motors to dynamically determine
      endosome identity and promote long-range organelle transport. Here we report that
      ankyrin-B (AnkB), through integrating all three systems, functions as a critical
      node in the protein circuitry underlying polarized recycling of alpha5beta1
      integrin in mouse embryonic fibroblasts, which enables persistent fibroblast
      migration along fibronectin gradients. AnkB associates with phosphatidylinositol
      3-phosphate (PI3P)-positive organelles in fibroblasts and binds dynactin to
      promote their long-range motility. We demonstrate that AnkB binds to Rab GTPase
      Activating Protein 1-Like (RabGAP1L) and recruits it to PI3P-positive organelles,
      where RabGAP1L inactivates Rab22A, and promotes polarized trafficking to the
      leading edge of migrating fibroblasts. We further determine that alpha5beta1
      integrin depends on an AnkB/RabGAP1L complex for polarized recycling. Our results
      reveal AnkB as an unexpected key element in coordinating polarized transport of
      alpha5beta1-integrin and likely of other specialized endocytic cargos.

PMID- 27718356
TI  - A widely employed germ cell marker is an ancient disordered protein with
      reproductive functions in diverse eukaryotes.
AB  - The advent of sexual reproduction and the evolution of a dedicated germline in
      multicellular organisms are critical landmarks in eukaryotic evolution. We report
      an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the
      earliest eukaryotes, and feature a rapidly evolving intrinsically disordered
      region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the
      major eukaryotic lineages diverged; GCNA predates the origin of a dedicated
      germline by a billion years. Gcna gene expression is enriched in reproductive
      cells across eukarya - either just prior to or during meiosis in single-celled
      eukaryotes, and in stem cells and germ cells of diverse multicellular animals.
      Studies of Gcna-mutant C. elegans and mice indicate that GCNA has functioned in
      reproduction for at least 600 million years. Homology to IDR-containing proteins
      implicated in DNA damage repair suggests that GCNA proteins may protect the
      genomic integrity of cells carrying a heritable genome.

PMID- 27718359
TI  - Projections from the lowest lumbar and sacral-caudal segments to the cerebellar
      cortex in the rat: An anterograde tracing study.
AB  - The crossed spinocerebellar tracts originate from neurons in the basolateral part
      of lamina V, the sacral nuclei of Stilling and the ventrolateral part of the
      ventral horn of the L6 to caudal segments. The present study examined their
      projection areas in the cerebellar cortex by using anterograde labeling of mossy
      fiber terminals with biotinylated dextran in the rat. Labeled terminals were
      distributed bilaterally in lobules I-V of the anterior lobe. They were most
      abundant in the apical parts of the lateral vermis and the intermediate region of
      lobules Ib and IIa, and the rostral side of lobule IIb. The number of labeled
      terminals in lobules Ib-IIb accounted for 56% and 81%, respectively, of the total
      9783 and 7045 labeled terminals. The number of labeled terminals decreased in
      lobules III to V. In the posterior lobe labeled terminals were distributed
      exclusively to lobules VIIIa and VIIIb and copula pyramidis. The present study
      demonstrates that spinocerebellar neurons of the sacral-caudal segments project
      primarily to the lateral part of lobules I and II, and less densely to lobules
      III-V and VIII, and copula pyramidis. The projection pattern was essentially
      similar to that observed in the cat.

PMID- 27718360
TI  - Does Mandibular Distraction Vector Influence Airway Volumes and Outcome?
AB  - PURPOSE: The goal of mandibular distraction in the Pierre-Robin sequence is to
      maximally expand the oropharyngeal airway. It has been hypothesized that a steep
      oblique distraction vector might allow greater airway enlargement compared with
      horizontal distraction. This study compared vector orientation in relation to
      airway volume and overall clinical outcome. MATERIALS AND METHODS: Micrognathic
      infants who underwent mandibular distraction with sufficient computed tomographic
      data were retrospectively reviewed. Demographic, diagnostic, perioperative, and
      distraction data were recorded. Groups were separated based on distraction vector
      (group 1, horizontal; group 2, oblique). Airway and mandibular volumes were
      measured using Mimics (Materialise, Leuven, Belgium). Morphologic and outcomes
      data were analyzed. Statistics involved 2-tailed t test, Pearson correlation, and
      analysis of covariance (ANCOVA). RESULTS: Mean age at distraction was 40 days,
      with devices maintained for 82 days on average. Fifty percent of patients were
      girls and 65% had cleft palate. Forty computed tomograms were analyzed. Airway
      (1,234 vs 3,501 mm3; P < .01) and mandibular (5,457 vs 11,827 mm3; P < .01)
      volumes, minimal airway area (12.5 vs 63.7 mm2; P < .01), and posterior airway
      space distance (2.3 vs 9.8 mm; P = .04) were significantly increased after
      distraction. Patients also had clinically improved sleep studies after
      distraction (apnea hypopnea index, 51.3 vs 5.5; P < .01). Vector analysis showed
      an average of 5.3 degrees  and 14.0 degrees  in groups 1 and 2, respectively (n =
      10 each). Intergroup analysis showed a trend toward increased airway volume in
      horizontal vectors (548 vs 255% of preoperative volume; P = .058), with slightly
      longer distraction length (20.3 vs 16.6 mm; P = .17). However, ANCOVA regression
      analysis showed no difference in the relation between vector and length. Other
      morphologic data and sleep study outcomes (apnea hypopnea index, 7.0 vs 3.9; P =
      .09) also were not statistically different between groups. Longer lengths of
      distraction correlated with narrower anterior mandibular angle and longer
      mandibular body length. CONCLUSIONS: Substantial airway enlargement occurs after
      mandibular distraction. Final airway volumes were similar between groups
      regardless of vector, which was confirmed by multivariate ANCOVA regression. The
      2 methods achieved airway stabilization, with clinical outcomes similar between
      the 2 groups.

PMID- 27718361
TI  - The regulation of human globin promoters by CCAAT box elements and the
      recruitment of NF-Y.
AB  - CCAAT boxes are motifs found within the proximal promoter of many genes,
      including the human globin genes. The highly conserved nature of CCAAT box motifs
      within the promoter region of both alpha-like and beta-like globin genes
      emphasises the functional importance of the CCAAT sequence in globin gene
      regulation. Mutations within the beta-globin CCAAT box result in beta
      thalassaemia, while mutations within the distal gamma-globin CCAAT box cause the
      Hereditary Persistence of Foetal Haemoglobin, a benign condition which results in
      continued gamma-globin expression during adult life. Understanding the
      transcriptional regulation of the globin genes is of particular interest, as
      reactivating the foetal gamma-globin gene alleviates the symptoms of beta
      thalassaemia and sickle cell anaemia. NF-Y is considered to be the primary
      activating transcription factor which binds to globin CCAAT box motifs. Here we
      review recruitment of NF-Y to globin CCAAT boxes and the role NF-Y plays in
      regulating globin gene expression. This article is part of a Special Issue
      entitled: Nuclear Factor Y in Development and Disease, edited by Prof. Roberto
      Mantovani.

PMID- 27718362
TI  - Corrigendum to "Functional basis of associative learning and its relationships
      with long-term potentiation evoked in the involved neural circuits: Lessons from
      studies in behaving mammals"[Neurobiol. Learn. Memory 124 (2015) 3-18].

PMID- 27718363
TI  - Structural pliability adjacent to the kinase domain highlights contribution of
      FAK1 IDRs to cytoskeletal remodeling.
AB  - Therapeutic protein kinase inhibitors are designed on the basis of kinase
      structures. Here, we define intrinsically disordered regions (IDRs) in
      structurally hybrid kinases. We reveal that 65% of kinases have an IDR adjacent
      to their kinase domain (KD). These IDRs are evolutionarily more conserved than
      IDRs distant to KDs. Strikingly, 36 kinases have adjacent IDRs extending into
      their KDs, defining a unique structural and functional subset of the kinome.
      Functional network analysis of this subset of the kinome uncovered FAK1 as
      topologically the most connected hub kinase. We identify that KD-flanking IDR of
      FAK1 is more conserved and undergoes more post-translational modifications than
      other IDRs. It preferentially interacts with proteins regulating scaffolding and
      kinase activity, which contribute to cytoskeletal remodeling. In summary,
      spatially and evolutionarily conserved IDRs in kinases may influence their
      functions, which can be exploited for targeted therapies in diseases including
      those that involve aberrant cytoskeletal remodeling.

PMID- 27718365
TI  - Breastfeeding Preterm Infants at a Neonatal Care Unit in Rural Tanzania.
AB  - OBJECTIVE: To describe the breastfeeding experiences of mothers with preterm and
      low-birth-weight infants in a neonatal unit in Tanzania. DESIGN: A qualitative
      research design. SETTING: A neonatal unit at a referral hospital in rural
      Tanzania. PARTICIPANTS: Convenience sample of 10 new mothers with preterm
      infants. Additionally, to triangulate the data, five nurses affiliated with the
      neonatal unit were interviewed. METHODS: A semistructured interview guide was
      used for data collection. All interviews were audiotaped and transcribed
      verbatim. Data were analyzed with inductive qualitative content analysis.
      RESULTS: One main category, The mother has to adapt to the new situation to make
      breastfeeding natural, and three generic categories, The challenges of
      breastfeeding a premature infant, Enhancing the feeding situation, and The need
      for support, were used to describe breastfeeding challenges. Challenges consisted
      of the perception that the infant was different than healthy infants and the
      infant's and mother's health problems and needs. To improve the feeding
      situation, mothers learned how to feed their infants using timing strategies.
      Confidence and security were achieved with support from family and friends, the
      other mothers, and the health care staff. CONCLUSION: Mothers perceived
      breastfeeding as natural but needed support to overcome the challenges of
      breastfeeding preterm infants. Through support and education they were empowered,
      adapted to their new situations, and felt confident with breastfeeding.

PMID- 27718364
TI  - Uptake and metabolism of fluorescent steroids by mycobacterial cells.
AB  - Fluorescent steroids BODIPY-cholesterol (BPCh) and 7-nitrobenzoxadiazole-4-amino
      (NBD)-labeled 22-NBD-chelesterol (22NC) as well as synthesized 20-(NBD)-pregn-5
      en-3beta-ol (20NP) were found to undergo bioconversions by Mycobacterium
      tuberculosis H37Rv and M. smegmatis mc2 155. The major fluorescent products were
      determined to be 4-en-3-one derivatives of the compounds. Degradation of NBD
      fluorophore was also detected in the cases of 22NC and 20NP, but neither NBD
      degradation nor steroidal part modification were observed for the synthesized 3
      (NBD)-cholestane. Mycobacterial 3beta-hydroxysteroid dehydrogenases were
      concluded to be responsible for the formation of the 4-en-3-one derivatives. All
      the compounds tested were found to cause staining both membrane lipids and
      cytosolic lipid droplets when incubated with mycobacteria in different manner,
      demonstrating ability of the steroids to reside in the compartments. The findings
      reveal a potential of the compounds for monitoring of steroid interactions with
      mycobacteria and provide information for design of new probes for this purpose.

PMID- 27718366
TI  - Expert Panel to Track Nurses' Effect on Maternal Morbidity and Mortality.
AB  - Rates of maternal morbidity and mortality in the United States have increased
      since 1990. Registered nurses are members of the health care work force who
      provide essential care to women during pregnancy, during birth, and after birth.
      Tools are needed to more effectively measure and track the effect of nursing care
      on maternal health outcomes. The Association of Women's Health, Obstetric and
      Neonatal Nurses and the Association of Maternal & Child Health Programs co
      convened an expert panel to develop a set of tools for use by public health and
      clinical leaders to support this effort.

PMID- 27718367
TI  - A Concept Analysis on the Use of Yakson in the NICU.
AB  - In the NICU context, Yakson is defined as a mother's gentle, nurturing, and
      soothing touch that is meant to comfort her newborn and results in the newborn's
      physically relaxed and emotionally stable condition, the mother's satisfaction
      and confidence, and stronger mother-infant interaction and attachment. Although
      this concept analysis is based on Korean culture, the understanding of Yakson can
      help nurses promote this feasible practice to enhance mother-infant interaction
      and attachment in the NICU.

PMID- 27718368
TI  - Vicarious Posttraumatic Growth in Labor and Delivery Nurses.
AB  - OBJECTIVE: To investigate vicarious posttraumatic growth in labor and delivery
      nurses who cared for women during traumatic births. DESIGN: A convergent parallel
      mixed-methods design was used. PARTICIPANTS: The sample consisted of 467 labor
      and delivery nurses who completed the quantitative portion and 295 (63%) who
      completed the qualitative portion of this mixed-methods study via the Internet.
      METHODS: The Association of Women's Health, Obstetric and Neonatal Nurses sent
      out e-mails to members who were labor and delivery nurses with a link to the
      electronic survey. Labor and delivery nurses completed the Posttraumatic Growth
      Inventory and the Core Beliefs Inventory in the quantitative portion. For the
      qualitative portion, the nurses were asked to describe their experiences of any
      positive changes in their beliefs or life as a result of their care for women
      during traumatic births. RESULTS: Labor and delivery nurses who cared for women
      during traumatic births reported a moderate amount of vicarious posttraumatic
      growth as indicated by their Posttraumatic Growth Inventory scores. Appreciation
      of Life was the dimension of the Posttraumatic Growth Inventory that reflected
      the highest growth, followed by Relating to Others, Personal Strength, Spiritual
      Change, and New Possibilities. In the qualitative findings, Relating to Others
      was also the dimension of posttraumatic growth most frequently described.
      CONCLUSION: We compared our results with those of previous studies in which
      researchers assessed vicarious posttraumatic growth in clinicians, and we found
      that labor and delivery nurses who cared for women during traumatic births
      experienced growth levels that were scored between the lowest and highest
      reported levels of therapists and social workers. Nurses need to be aware of the
      potential to experience this growth despite the significant stress and
      unpredictability of the labor and delivery environment, which could decrease
      burnout and improve retention rates.

PMID- 27718370
TI  - Eicosapentaenoic acid reduces membrane fluidity, inhibits cholesterol domain
      formation, and normalizes bilayer width in atherosclerotic-like model membranes.
AB  - Cholesterol crystalline domains characterize atherosclerotic membranes, altering
      vascular signaling and function. Omega-3 fatty acids reduce membrane lipid
      peroxidation and subsequent cholesterol domain formation. We evaluated non
      peroxidation-mediated effects of eicosapentaenoic acid (EPA), other TG-lowering
      agents, docosahexaenoic acid (DHA), and other long-chain fatty acids on membrane
      fluidity, bilayer width, and cholesterol domain formation in model membranes. In
      membranes prepared at 1.5:1 cholesterol-to-phospholipid (C/P) mole ratio
      (creating pre-existing domains), EPA, glycyrrhizin, arachidonic acid, and alpha
      linolenic acid promoted the greatest reductions in cholesterol domains (by 65.5%,
      54.9%, 46.8%, and 45.2%, respectively) compared to controls; other treatments had
      modest effects. EPA effects on cholesterol domain formation were dose-dependent.
      In membranes with 1:1 C/P (predisposing domain formation), DHA, but not EPA, dose
      dependently increased membrane fluidity. DHA also induced cholesterol domain
      formation without affecting temperature-induced changes in-bilayer unit cell
      periodicity relative to controls (d-space; 57A-55A over 15-30 degrees C).
      Together, these data suggest simultaneous formation of distinct cholesterol-rich
      ordered domains and cholesterol-poor disordered domains in the presence of DHA.
      By contrast, EPA had no effect on cholesterol domain formation and produced
      larger d-space values relative to controls (60A-57A; p<0.05) over the same
      temperature range, suggesting a more uniform maintenance of lipid dynamics
      despite the presence of cholesterol. These data indicate that EPA and DHA had
      different effects on membrane bilayer width, membrane fluidity, and cholesterol
      crystalline domain formation; suggesting omega-3 fatty acids with differing chain
      length or unsaturation may differentially influence membrane lipid dynamics and
      structural organization as a result of distinct phospholipid/sterol interactions.

PMID- 27718369
TI  - Change in cytokine levels is not associated with rapid antidepressant response to
      ketamine in treatment-resistant depression.
AB  - Several pro-inflammatory cytokines have been implicated in depression and in
      antidepressant response. This exploratory analysis assessed: 1) the extent to
      which baseline cytokine levels predicted positive antidepressant response to
      ketamine; 2) whether ketamine responders experienced acute changes in cytokine
      levels not observed in non-responders; and 3) whether ketamine lowered levels of
      pro-inflammatory cytokines, analogous to the impact of other antidepressants.
      Data from double-blind, placebo-controlled studies of patients with major
      depressive disorder (MDD) or bipolar disorder (BD) who received a single infusion
      of sub-anesthetic dose ketamine were used (N = 80). Plasma levels of the eight
      cytokines were measured at baseline and at 230 min, 1 day, and 3 days post
      ketamine. A significant positive correlation was observed between sTNFR1 and
      severity of depression at baseline. Cytokine changes did not correlate with
      changes in mood nor predict mood changes associated with ketamine administration.
      Ketamine significantly increased IL-6 levels and significantly decreased sTNFR1
      levels. IL-6 and TNF-alpha levels were also significantly higher-and sTNFR1
      levels were significantly lower-in BD compared to MDD subjects. The functional
      significance of this difference is unknown. Changes in cytokine levels post
      ketamine were not related to antidepressant response, suggesting they are not a
      primary mechanism involved in ketamine's acute antidepressant effects. Taken
      together, the results suggest that further study of cytokine levels is warranted
      to assess their potential role as a surrogate outcome in the rapid antidepressant
      response paradigm.

PMID- 27718371
TI  - Has the great recession and its aftermath reduced traffic fatalities?
AB  - An analysis of state-level data from 1984 to 2014 provides evidence on the
      relationship between economic recessions and US traffic fatalities. While there
      are large reductions associated with decreases in household median income, other
      policy variables tend to have additional and in some cases, larger effects. An
      increase in the inequality of the income distribution, measured by the Gini
      index, has reduced traffic fatalities. Graduated licensing policies, cell phone
      laws, and motorcycle helmet requirements are all associated with reductions in
      fatalities. Other factors include a proxy for medical technology, and access to
      emergency medical services (based on the percent of vehicle miles traveled in
      rural areas); reductions in the latter accounted for a substantial reduction in
      fatalities and is likely another indicator of reduced economic activity. Changes
      in the road network, mainly increases in the percent of collector roads has
      increased fatalities. Population growth is associated with increased traffic
      fatalities and changes in age cohorts has a small negative effect. Overall,
      results suggest that there has been a beneficial impact on traffic fatalities
      from reduced economic activity, but various policies adopted by the states have
      also reduced traffic fatalities.

PMID- 27718373
TI  - The association between serum cathepsin L and mortality in older adults.
AB  - BACKGROUND AND AIMS: Research suggests that the protease cathepsin L is causally
      involved in atherosclerosis. However, data on cathepsin L as a risk marker are
      lacking. Therefore, we investigated associations between circulating cathepsin L
      and cardiovascular mortality. METHODS: Two independent community-based cohorts
      were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77
      years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up,
      and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n =
      993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths
      during 10.0 years follow-up. RESULTS: Higher serum cathepsin L was associated
      with an increased risk for cardiovascular mortality in age- and sex-adjusted
      models in both cohorts (ULSAM: hazard ratio (HR) for 1-standard deviation (SD)
      increase, 1.17 [95% CI, 1.01-1.34], p = 0.032 PIVUS: HR 1.35 [95% CI, 1.07-1.72],
      p = 0.013). When merging the cohorts, these associations were independent of
      inflammatory markers and cardiovascular risk factors, but non-significant
      adjusting for kidney function. Individuals with a combination of elevated
      cathepsin L and increased inflammation, kidney dysfunction, or prevalent
      cardiovascular disease had a markedly increased risk, while no increased risk was
      associated with elevated cathepsin L, in the absence of these disease states.
      CONCLUSIONS: An association between higher serum cathepsin L and increased risk
      of cardiovascular mortality was found in two independent cohorts. Impaired kidney
      function appears to be an important moderator or mediator of these associations.
      Further studies are needed to delineate the underlying mechanisms and to evaluate
      whether the measurement of cathepsin L might have clinical utility.

PMID- 27718372
TI  - Carotid plaque fissure: An underestimated source of intraplaque hemorrhage.
AB  - BACKGROUND AND AIMS: Plaque fissuring, a phenomenon morphologically distinct from
      the classical rupture of a thinned fibrous cap, has not been well characterized
      in carotid atherosclerosis. The aim of this study was to establish the prevalence
      of plaque fissures in advanced carotid plaques with an otherwise intact luminal
      surface, and to determine whether they might be a source of intraplaque
      hemorrhage (IPH). METHODS: We evaluated 244 surgically intact, 'en bloc'
      embedded, serially sectioned carotid endarterectomy specimens and included only
      those plaques with a grossly intact luminal surface. RESULTS: Among the 67
      plaques with grossly intact luminal surface, cap fissure was present in 39 (58%)
      plaques. A total of 60 individual fissures were present, and longitudinally mean
      fissure length was 1.3 mm. Most fissures were found distal to the bifurcation
      (63%), proximal to the stenosis (88%), and in the posterior (opposite the flow
      divider) or lateral quadrants (80%). 36% of the fissures remained in the
      superficial third of the plaque. 52% extended from the lumen surface to the
      middle third of the plaque and 12% reached the outer third of the plaque on cross
      section. Fissures often occurred between two tissue planes and were connected to
      IPH (fresh: 63%; any type: 92%) and calcifications (43%). No correlation was
      found with patient characteristics such as symptom status, carotid stenosis,
      hypertension, diabetes, smoking and medications (statins or antiplatelet agents).
      CONCLUSIONS: Plaque fissures are common in advanced carotid plaques with an
      otherwise grossly intact luminal surface and are associated with fresh
      intraplaque hemorrhage. As they occur on the interface between plaque components
      with different mechanical properties, further biomechanical studies are needed to
      unravel the underlying failure mechanisms.

PMID- 27718375
TI  - Screen for genes involved in radiation survival of Escherichia coli and
      construction of a reference database.
AB  - A set of 3907 single-gene knockout (Keio collection) strains of Escherichia coli
      K-12 was examined for strains with increased susceptibility to killing by X- or
      UV-radiation. After screening with a high-throughput resazurin-based assay and
      determining radiation survival with triplicate clonogenic assays, we identified
      76 strains (and associated deleted genes) showing statistically-significant
      increased radiation sensitivity compared to a control strain. To determine gene
      novelty, we constructed a reference database comprised of genes found in nine
      similar studies including ours. This database contains 455 genes comprised of 103
      common genes (found 2-7 times), and 352 uncommon genes (found once). Our 76 genes
      includes 43 common genes and 33 uncommon (potentially novel) genes, i.e., appY,
      atoS, betB, bglJ, clpP, cpxA, cysB, cysE, ddlA, dgkA, dppF, dusB, elfG, eutK,
      fadD, glnA, groL, guaB, intF, prpR, queA, rplY, seqA, sufC,yadG, yagJ, yahD,
      yahO, ybaK, ybfA, yfaL, yhjV, and yiaL. Of our 33 uncommon gene mutants, 4 (12%)
      were sensitive only to UV-radiation, 10 (30%) only to X-radiation, and 19 (58%)
      to both radiations. Our uncommon mutants vs. our common mutants showed more
      radiation specificity, i.e., 12% vs. 9% (sensitive only to UV-); 30% vs. 16% (X-)
      and 58% vs. 74% (both radiations). Considering just our radiation-sensitive
      mutants, the median UV-radiation survival (75Jm-2) for 23 uncommon mutants was
      6.84E-3 compared to 1.85E-3 for 36 common mutants (P=0.025). Similarly, the
      average X-radiation survival for 29 uncommon mutants was 1.08E-2, compared to
      6.19E-3 for 39 common mutants (P=0.010). Comparing gene functions using MultiFun
      terms, uncommon genes tended to show less involvement in DNA repair-relevant
      categories (information transfer and cell processes), but greater involvement in
      seven other categories. Our analysis of 455 genes suggests cell survival and DNA
      repair processes are more complex than previously understood, and may be
      compromised by deficiencies in other processes.

PMID- 27718374
TI  - Patient-reported outcomes and visual acuity after 12months of anti-VEGF-treatment
      for sight-threatening diabetic macular edema in a real world setting.
AB  - AIMS: To examine objective visual acuity measured with ETDRS, retinal thickness
      (OCT), patient reported outcome and describe levels of glycated hemoglobin and
      its association with the effects on visual acuity in patients treated with anti
      VEGF for visual impairment due to diabetic macular edema (DME) during 12months in
      a real world setting. METHODS: In this cross-sectional study, 58 patients (29
      females and 29 males; mean age, 68years) with type 1 and type 2 diabetes
      diagnosed with DME were included. Medical data and two questionnaires were
      collected; an eye-specific (NEI VFQ-25) and a generic health-related quality of
      life questionnaire (SF-36) were used. RESULTS: The total patient group had
      significantly improved visual acuity and reduced retinal thickness at 4months and
      remains at 12months follow up. Thirty patients had significantly improved visual
      acuity, and 27 patients had no improved visual acuity at 12months. The patients
      with improved visual acuity had significantly improved scores for NEI VFQ-25
      subscales including general health, general vision, near activities, distance
      activities, and composite score, but no significant changes in scores were found
      in the group without improvements in visual acuity. CONCLUSIONS: Our study
      revealed that anti-VEGF treatment improved visual acuity and central retinal
      thickness as well as patient-reported outcome in real world 12months after
      treatment start.

PMID- 27718376
TI  - Helical comb magnetostrictive patch transducers for inspecting spiral welded
      pipes using flexural guided waves.
AB  - A wavefront analysis indicates that a flexural wave propagates at a helix angle
      with respect to the pipe axis. The expression for calculation of the helix angle
      for each flexural mode is given, and the helix angle dispersion curves for
      flexural modes are calculated. According to the new understanding of flexural
      guided waves, a helical comb magnetostrictive patch transducer (HCMPT) is
      proposed for selectively exciting a single predominant flexural torsional guided
      wave in a pipe and inspecting spiral welded pipes using flexural waves. A HCMPT
      contains a pre-magnetized magnetostrictive patch that is helically coupled with
      the outer surface of a pipe, and a novel compound comb coil that is wrapped
      around the helical magnetostrictive patch. The proposed wideband HCMPT possesses
      the direction control ability. A verification experiment indicates that flexural
      torsional mode T(3,1) at center frequency f=64kHz is effectively actuated by a
      HCMPT with 13-degree helix angle. Flexural torsional modes T(N,1) with
      circumferential order N equals 1-5 are selected to inspect a seamless steel pipe,
      artificial defects are effectively detected by the proposed HCMPT. A 20-degree
      HCMPT is adopted to inspect a spiral welded pipe, an artificial notch with cross
      section loss CSL=2.7% is effectively detected by using flexural waves.

PMID- 27718377
TI  - Dissimilar trend of nonlinearity in ultrasound transducers and systems at
      resonance and non-resonance frequencies.
AB  - Several factors can affect performance of an ultrasound system such as quality of
      excitation signal and ultrasound transducer behaviour. Nonlinearity of
      piezoelectric ultrasound transducers is a key determinant in designing a proper
      driving power supply. Although, the nonlinearity of piezoelectric transducer
      impedance has been discussed in different literatures, the trend of the
      nonlinearity at different frequencies with respect to excitation voltage
      variations has not been clearly investigated in practice. In this paper, to
      demonstrate how the nonlinearity behaves, a sandwich piezoceramic transducer was
      excited at different frequencies. Different excitation signals were generated
      using a linear power amplifier and a multilevel converter within a range of 30
      200V. Empirical relation was developed to express the resistance of the
      piezoelectric transducer as a nonlinear function of both excitation voltage and
      resonance frequency. The impedance measurements revealed that at higher voltage
      ranges, the piezoelectric transducer can be easily saturated. Also, it was shown
      that for the developed ultrasound system composed of two transducers (one
      transmitter and one receiver), the output voltage measured across receiver is a
      function of a voltage across the resistor in the RLC branches and is related to
      the resonance frequencies of the ultrasound transducer.

PMID- 27718378
TI  - Nonlinear imaging (NIM) of flaws in a complex composite stiffened panel using a
      constructive nonlinear array (CNA) technique.
AB  - Recently, there has been high interest in the capabilities of nonlinear
      ultrasound techniques for damage/defect detection as these techniques have been
      shown to be quite accurate in imaging some particular type of damage. This paper
      presents a Constructive Nonlinear Array (CNA) method, for the detection and
      imaging of material defects/damage in a complex composite stiffened panel. CNA
      requires the construction of an ultrasound array in a similar manner to standard
      phased arrays systems, which require multiple transmitting and receiving
      elements. The method constructively phase-match multiple captured signals at a
      particular position given multiple transmit positions, similar to the total
      focusing method (TFM) method. Unlike most of the ultrasonic linear techniques, a
      longer excitation signal was used to achieve a steady-state excitation at each
      capturing position, so that compressive and tensile stress at defect/crack
      locations increases the likelihood of the generation of nonlinear elastic waves.
      Moreover, the technique allows the reduction of instrumentation nonlinear wave
      generation by relying on signal attenuation to naturally filter these errors.
      Experimental tests were carried out on a stiffened panel with manufacturing
      defects. Standard industrial linear ultrasonic test were carried out for
      comparison. The proposed new method allows to image damages/defects in a reliable
      and reproducible manner and overcomes some of the main limitations of nonlinear
      ultrasound techniques. In particular, the effectiveness and robustness of CNA and
      the advantages over linear ultrasonic were clearly demonstrated allowing a better
      resolution and imaging of complex and realistic flaws.

PMID- 27718379
TI  - Negative emotional reactivity moderates the relations between family cohesion and
      internalizing and externalizing symptoms in adolescence.
AB  - Lower family cohesion is associated with adolescent internalizing and
      externalizing problems. However, there are likely individual differences in
      youth's responses to family processes. For example, adolescents higher in
      negative emotional reactivity, who often exhibit elevated physiological
      responsivity to context, may be differentially affected by family cohesion. We
      explored whether youth's negative emotional reactivity moderated the relation
      between family cohesion and youth's symptoms and tested whether findings were
      consistent with the diathesis-stress model or differential susceptibility
      hypothesis. Participants were 651 adolescents (M = 12.99 +/- .95 years old; 72%
      male) assessed at two time points (Time 1, ages 12-14; Time 2, age 16) in
      Pittsburgh, PA. At Time 1, mothers reported on family cohesion and youth reported
      on their negative emotional reactivity. At Time 2, youth reported on their
      symptoms. Among youth higher in negative emotional reactivity, lower family
      cohesion predicted higher symptoms than higher family cohesion, consistent with
      the diathesis-stress model.

PMID- 27718381
TI  - Molecular characterization of lake sediment WEON by Fourier transform ion
      cyclotron resonance mass spectrometry and its environmental implications.
AB  - The compositional properties of water-extractable organic nitrogen (WEON) affect
      its behavior in lake ecosystems. This work is the first comprehensive study using
      Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for the
      characterization of the molecular composition of WEON in lake sediment. In
      sediments of Erhai Lake in China, this study found complex WEON species, with N
      containing compounds in the northern, central, and southern regions contributing
      34.47%, 42.44%, and 40.6%, respectively, of total compounds. Additionally, a van
      Krevelen diagram revealed that lignin components were dominant in sediment WEON
      structures (68% of the total), suggesting terrestrial sources. Furthermore, this
      study applied ESI-FT-ICR-MS to the examination of the environmental processes of
      lake sediment WEON on a molecular level. The results indicated that sediment
      depth impacted WEON composition and geochemical processes. Compared with other
      ecosystems, the double bond equivalent (DBE) value was apparently lower in Erhai
      sediment, indicating the presence of relatively fewer and smaller aromatic
      compounds. In addition, the presence of a large number of N-containing species
      and abundant oxidized nitrogen functional compounds that were likely to
      biodegrade may have further increased the potential releasing risk of WEON from
      Erhai sediment under certain environmental conditions.

PMID- 27718380
TI  - The sense of relational entitlement among adolescents toward their parents
      (SREap) - Testing an adaptation of the SRE.
AB  - The quality of the adolescent-parent relationship is closely related to the
      adolescent's sense of entitlement. Study 1 (458 central-Israel adolescents, 69%
      girls, ages: 11-16) developed the sense of relational entitlement among
      adolescents toward their parents (SREap, adapted from the original SRE on adults'
      romantic relationships) and provided initial validity evidence of its three
      factor structure: exaggerated, restricted and assertive - replicating the SRE's
      factor structure. Studies 2-5 (1237 adolescents, 56% girls) examined the link
      between the SREap factors and relevant psychological measures. Exaggerated and
      restricted SREap factors were associated with attachment insecurities. Restricted
      and exaggerated entitlement factors were related to higher levels of emotional
      problems, and lower levels of: wellbeing, positive mood and life satisfaction.
      Conversely, assertive entitlement was related to higher life satisfaction and
      self-efficacy and lower levels of emotional problems. The findings also indicate
      that SREap is not merely a form of narcissism. The implications of SREap are
      discussed.

PMID- 27718382
TI  - Determination of recharge fraction of injection water in combined abstraction
      injection wells using continuous radon monitoring.
AB  - The recharge fractions of injection water in combined abstraction-injection wells
      (AIW) were determined using continuous radon monitoring and radon mass balance
      model. The recharge system consists of three combined abstraction-injection
      wells, an observation well, a collection tank, an injection tank, and tubing for
      heating and transferring used groundwater. Groundwater was abstracted from an AIW
      and sprayed on the water-curtain heating facility and then the used groundwater
      was injected into the same AIW well by the recharge system. Radon concentrations
      of fresh groundwater in the AIWs and of used groundwater in the injection tank
      were measured continuously using a continuous radon monitoring system. Radon
      concentrations of fresh groundwater in the AIWs and used groundwater in the
      injection tank were in the ranges of 10,830-13,530 Bq/m3 and 1500-5600 Bq/m3,
      respectively. A simple radon mass balance model was developed to estimate the
      recharge fraction of used groundwater in the AIWs. The recharge fraction in the 3
      AIWs was in the range of 0.595-0.798. The time series recharge fraction could be
      obtained using the continuous radon monitoring system with a simple radon mass
      balance model. The results revealed that the radon mass balance model using
      continuous radon monitoring was effective for determining the time series
      recharge fractions in AIWs as well as for characterizing the recharge system.

PMID- 27718383
TI  - Considering DNA damage when interpreting mtDNA heteroplasmy in deep sequencing
      data.
AB  - Resolution of mitochondrial (mt) DNA heteroplasmy is now possible when applying a
      massively parallel sequencing (MPS) approach, including minor components down to
      1%. However, reporting thresholds and interpretation criteria will need to be
      established for calling heteroplasmic variants that address a number of important
      topics, one of which is DNA damage. We assessed the impact of increasing amounts
      of DNA damage on the interpretation of minor component sequence variants in the
      mtDNA control region, including low-level mixed sites. A passive approach was
      used to evaluate the impact of storage conditions, and an active approach was
      employed to accelerate the process of hydrolytic damage (for example, replication
      errors associated with depurination events). The patterns of damage were compared
      and assessed in relation to damage typically encountered in poor quality samples.
      As expected, the number of miscoding lesions increased as conditions worsened.
      Single nucleotide polymorphisms (SNPs) associated with miscoding lesions were
      indistinguishable from innate heteroplasmy and were most often observed as 1-2%
      of the total sequencing reads. Numerous examples of miscoding lesions above 2%
      were identified, including two complete changes in the nucleotide sequence,
      presenting a challenge when assessing the placement of reporting thresholds for
      heteroplasmy. To mitigate the impact, replication of miscoding lesions was not
      observed in stored samples, and was rarely seen in data associated with
      accelerated hydrolysis. In addition, a significant decrease in the expected
      transition:transversion ratio was observed, providing a useful tool for
      predicting the presence of damage-induced lesions. The results of this study
      directly impact MPS analysis of minor sequence variants from poorly preserved DNA
      extracts, and when biological samples have been exposed to agents that induce DNA
      damage. These findings are particularly relevant to clinical and forensic
      investigations.

PMID- 27718384
TI  - Advanced midwifery practice: An evolutionary concept analysis.
AB  - AIM: the concept of 'advanced midwifery practice' is explored to a limited extent
      in the international literature. However, a clear conception of advanced
      midwifery practice is vital to advance the discipline and to achieve both
      internal and external legitimacy. This concept analysis aims to clarify advanced
      midwifery practice and identify its components. METHODS: a review of the
      literature was executed using Rodgers' evolutionary method of concept analysis to
      analyze the attributes, references, related terms, antecedents and consequences
      of advanced midwifery practice. RESULTS: an international consensus definition of
      advanced midwifery practice is currently lacking. Four major attributes of
      advanced midwife practitioners (AMPs) are identified: autonomy in practice,
      leadership, expertise, and research skills. A consensus was found on the need of
      preparation at master's level for AMPs. Such midwives have a broad and
      internationally varied scope of practice, fulfilling different roles such as
      clinicians, clinical and professional leaders, educators, consultants, managers,
      change agents, researchers, and auditors. Evidence illustrating the important
      part AMPs play on a clinical and strategic level is mounting. KEY CONCLUSIONS:
      the findings of this concept analysis support a wide variety in the emergence,
      titles, roles, and scope of practice of AMPs. Research on clinical and strategic
      outcomes of care provided by AMPs supports further implementation of these roles.
      As the indistinctness of AMPs' titles and roles is one of the barriers for
      implementation, a clear conceptualization of advanced midwifery practice seems
      essential for successful implementation. IMPLICATIONS FOR PRACTICE: an
      international debate and consensus on the defining elements of advanced midwifery
      practice could enhance the further development of midwifery as a profession and
      is a prerequisite for its successful implementation. Due to rising numbers of
      AMPs, extension of practice and elevated quality requirements in healthcare, more
      outcomes research exclusively evaluating the contribution of AMPs to healthcare
      becomes possible and desirable.

PMID- 27718385
TI  - Tuberculosis around the tarsal navicular: A rare entity.
AB  - Osteoarticular TB around the tarsal navicular is a chronic, uncommon condition
      affecting the midfoot, which causes significant morbidity to the patient.
      Tuberculosis around the tarsal navicular is rarely described in the literature. A
      series of three cases - two involving the talo-navicular joint and one involving
      the naviculo-cuneiform joint is described. Biopsy was used in all the cases for
      achieving diagnosis. All patients had good to fair outcome following medical
      management with anti-tubercular therapy. Due to the pauci-bacillary nature of the
      disease, a positive culture of the disease is not always possible. The diagnosis
      depends on a positive histopathology finding. Once an early diagnosis is
      achieved, antitubercular therapy is usually the mainstay. Clinical awareness of
      the rare presentations of this disease can help in early detection, adequate
      treatment and good to fair outcomes. Due to the destruction of the midfoot
      joints, some patients report difficulty in walking on uneven surfaces and
      barefoot, for which triple arthrodesis may be offered.

PMID- 27718386
TI  - The burden of diabetes-related foot disorders in community-dwellers living in
      rural Ecuador: Results of the Atahualpa Project.
AB  - BACKGROUND/OBJECTIVES: Prevalence of diabetes-related foot disorders (DRFD) in
      rural areas of developing countries is unknown. The burden of these conditions in
      Atahualpa, a rural Ecuadorian village, were assessed. METHODS: Using a population
      based design, Atahualpa residents aged >=40 years with diabetes mellitus were
      identified. Ankle brachial index determinations were used to assess presence of
      peripheral arterial disease, and the Michigan Neuropathy Screening Instrument was
      used to estimate peripheral neuropathy. Ulcers in the foot/ankle as well as
      history of amputations were considered as evidence of active diabetic foot
      disease. Using a linear model of risk, factors that independently correlated with
      DRFD, were assessed. RESULTS: Mean age of 110 participants was 64+/-12years (59%
      women). Peripheral arterial disease was diagnosed in 24% of cases and peripheral
      neuropathy in 59% (15% had both conditions). In the adjusted model, increasing
      age and being men increased the risk for DRFD. Active diabetic foot disease was
      noted in 7% of participants, and another 60% were at moderate-to-high risk for
      developing this complication (according to NHS Borders Foot Classification
      System). CONCLUSIONS: The prevalence of DRFD is high in rural Ecuador, and most
      of the affected individuals are at risk for developing active diabetic foot
      disease.

PMID- 27718387
TI  - The cross-cultural (transcultural) adaptation and validation of the nursing image
      questionnaire.
AB  - Education of nurses in the Republic of Croatia is being developed as a result of
      compliance with education in the European Union and the implementation of nursing
      research that leads to the growth of the whole profession. However, prejudice
      against the nursing profession is still present and therefore it is necessary to
      explore the attitudes of the general population and the population of nurses in
      the nursing profession in order to discover the causes of such prejudices and act
      on them. Therefore, the aim of this paper was to present transcultural adaptation
      and validation of the Nursing Image Questionnaire, which was created by Toth and
      associates (1998). The questionnaire, which includes 30 items and measures how an
      individual looks at the roles, values, and professional activities of nurses, was
      conducted as part of a preliminary study and was culturally adapted. The final
      study included 905 students who in 2011 and 2012 enrolled in the first year of
      full-time and part-time nursing study; the questionnaire was completed by 725
      students. Toth and associates assumed that the attitude toward nursing is
      expressed as the sum of the responses of all the items, which would mean a factor
      structure with high item intercorrelation, but they also split the questionnaire
      into five thematic units. Results showed that, contrary to expectations,
      intercorrelations of items were extremely low and that following the completion
      of factor analysis, no satisfactory construct validity was established. From the
      obtained results, it can be concluded that it is not justified to create a latent
      dimension as established by research of Toth and associates, and the items,
      although there is a correlation between some of them, should be interpreted and
      analysed as independent constructs.

PMID- 27718389
TI  - Delay-distribution-dependent Hinfinity state estimation for delayed neural
      networks with (x,v)-dependent noises and fading channels.
AB  - This paper deals with the Hinfinity state estimation problem for a class of
      discrete-time neural networks with stochastic delays subject to state- and
      disturbance-dependent noises (also called (x,v)-dependent noises) and fading
      channels. The time-varying stochastic delay takes values on certain intervals
      with known probability distributions. The system measurement is transmitted
      through fading channels described by the Rice fading model. The aim of the
      addressed problem is to design a state estimator such that the estimation
      performance is guaranteed in the mean-square sense against admissible stochastic
      time-delays, stochastic noises as well as stochastic fading signals. By employing
      the stochastic analysis approach combined with the Kronecker product, several
      delay-distribution-dependent conditions are derived to ensure that the error
      dynamics of the neuron states is stochastically stable with prescribed Hinfinity
      performance. Finally, a numerical example is provided to illustrate the
      effectiveness of the obtained results.

PMID- 27718388
TI  - The role of galectin-1 in in vitro and in vivo photodynamic therapy with a
      galactodendritic porphyrin.
AB  - Conventional photodynamic agents used in clinic are porphyrin-based
      photosensitizers. However, they have low tumour selectivity, which may induce
      unwanted side-effects and damage to healthy tissues. In this study, we used a
      porphyrin with dendritic units of galactose (PorGal8) developed by us, which can
      target the galactose-binding protein, galectin-1, known to be overexpressed in
      many tumour tissues. In vitro and in vivo studies had been conducted for the
      validation of PorGal8 effectiveness. We showed a specific uptake of PorGal8 and
      induction of apoptotic cell death by generating oxidative stress and alterations
      in the cytoskeleton of bladder cancer cells overexpressing galectin-1. We further
      validated the photodynamic efficiency of PorGal8 in athymic nude mice (Balb/c
      nu/nu) bearing subcutaneously implanted luciferase-positive bladder cancer
      xenografts, overexpressing galectin-1 protein. PorGal8 (5 MUmol/kg,
      intraperitoneal), injected 24 h before light delivery (50.4 J/cm2), inhibited
      tumour growth. We conclude that the use of PorGal8 enables selective target and
      cytotoxicity by photodynamic therapy in cancer cells overexpressing galectin-1,
      preventing undesired phototoxicity in the surrounding healthy tissues.

PMID- 27718390
TI  - A neurodynamic approach to convex optimization problems with general constraint.
AB  - This paper presents a neurodynamic approach with a recurrent neural network for
      solving convex optimization problems with general constraint. It is proved that
      for any initial point, the state of the proposed neural network reaches the
      constraint set in finite time, and converges to an optimal solution of the convex
      optimization problem finally. In contrast to the existing related neural
      networks, the convergence rate of the state of the proposed neural network can be
      calculated quantitatively via the Lojasiewicz exponent under some mild
      assumptions. As applications, we estimate explicitly some Lojasiewicz exponents
      to show the convergence rate of the state of the proposed neural network for
      solving convex quadratic optimization problems. And some numerical examples are
      given to demonstrate the effectiveness of the proposed neural network.

PMID- 27718391
TI  - Multistability of complex-valued neural networks with discontinuous activation
      functions.
AB  - In this paper, based on the geometrical properties of the discontinuous
      activation functions and the Brouwer's fixed point theory, the multistability
      issue is tackled for the complex-valued neural networks with discontinuous
      activation functions and time-varying delays. To address the network with
      discontinuous functions, Filippov solution of the system is defined. Through
      rigorous analysis, several sufficient criteria are obtained to assure the
      existence of 25n equilibrium points. Among them, 9n points are locally stable and
      16n-9n equilibrium points are unstable. Furthermore, to enlarge the attraction
      basins of the 9n equilibrium points, some mild conditions are imposed. Finally,
      one numerical example is provided to illustrate the effectiveness of the obtained
      results.

PMID- 27718392
TI  - A Self-Organizing Incremental Neural Network based on local distribution
      learning.
AB  - In this paper, we propose an unsupervised incremental learning neural network
      based on local distribution learning, which is called Local Distribution Self
      Organizing Incremental Neural Network (LD-SOINN). The LD-SOINN combines the
      advantages of incremental learning and matrix learning. It can automatically
      discover suitable nodes to fit the learning data in an incremental way without a
      priori knowledge such as the structure of the network. The nodes of the network
      store rich local information regarding the learning data. The adaptive vigilance
      parameter guarantees that LD-SOINN is able to add new nodes for new knowledge
      automatically and the number of nodes will not grow unlimitedly. While the
      learning process continues, nodes that are close to each other and have similar
      principal components are merged to obtain a concise local representation, which
      we call a relaxation data representation. A denoising process based on density is
      designed to reduce the influence of noise. Experiments show that the LD-SOINN
      performs well on both artificial and real-word data.

PMID- 27718393
TI  - The effects of fatigue on lower extremity kinematics, kinetics and joint coupling
      in symptomatic female runners with iliotibial band syndrome.
AB  - BACKGROUND: Altered hip and knee kinematics and joint coupling have been
      documented in runners with iliotibial band syndrome. Symptoms often present
      themselves after several minutes of running, yet the effect of fatigue warrants
      further exploration. The purpose of this study was to determine the effect of a
      run to fatigue in runners with iliotibial band syndrome, as compared to healthy
      controls. METHODS: Twenty uninjured and 12 female runners with iliotibial band
      syndrome performed a treadmill run to fatigue. Prior-to and following a run to
      fatigue, overground running data were collected. Variables of interest included
      stance phase: peak hip adduction and internal rotation, peak hip abductor and
      external rotator joint moments and frontal-sagittal plane hip and knee joint
      coupling. FINDINGS: Fatigue resulted in decreased peak hip adduction angles in
      injured runners. Fatigue did not affect injured runners differently than controls
      with respect to the remaining variables. Coupling differences did not exist
      between healthy and injured runners with respect to the loading or propulsive
      phases of stance. INTERPRETATION: While clinicians often strengthen hip abductor
      muscles and provide gait re-training to decrease stance phase hip adduction, our
      results suggest that, when exerted, female runners with iliotibial band syndrome
      independently modify their running gait to decrease hip adduction, potentially as
      a result of pain. Fatigue did not have an effect on the remaining study
      variables. It is possible that reducing the length of the iliotibial band through
      minimizing hip adduction reduces pain, but the other variables examined are not
      sensitive to this phenomenon.

PMID- 27718394
TI  - Particle-based N-linked glycan analysis of selected proteins from biological
      samples using nonglycosylated binders.
AB  - Glycosylation is one of the most common and important post-translational
      modifications, influencing both the chemical and the biological properties of
      proteins. Studying the glycosylation of the entire protein population of a sample
      can be challenging because variations in the concentrations of certain proteins
      can enhance or obscure changes in glycosylation. Furthermore, alterations in the
      glycosylation pattern of individual proteins, exhibiting larger variability in
      disease states, have been suggested as biomarkers for different types of cancer,
      as well as inflammatory and neurodegenerative diseases. In this paper, we present
      a rapid and efficient method for glycosylation analysis of individual proteins
      focusing on changes in the degree of fucosylation or other alterations to the
      core structure of the glycans, such as the presence of bisecting N
      acetylglucosamines and a modified degree of branching. Streptavidin-coated
      magnetic beads are used in combination with genetically engineered immunoaffinity
      binders, called VHH antibody fragments. A major advantage of the VHHs is that
      they are nonglycosylated; thus, enzymatic release of glycans from the targeted
      protein can be performed directly on the beads. After deglycosylation, the
      glycans are analyzed by MALDI-TOF-MS. The developed method was evaluated
      concerning its specificity, and thereafter implemented for studying the
      glycosylation pattern of two different proteins, alpha-1-antitrypsin and
      transferrin, in human serum and cerebrospinal fluid. To our knowledge, this is
      the first example of a protein array-type experiment that employs bead-based
      immunoaffinity purification in combination with mass spectrometry analysis for
      fast and efficient glycan analysis of individual proteins in biological fluid.

PMID- 27718395
TI  - Lichenysin-geminal amino acid-based surfactants: Synergistic action of an
      unconventional antimicrobial mixture.
AB  - Recently it has been demonstrated that catanionic mixtures of oppositely charged
      surfactants have improved physicochemical-biological properties compared to the
      individual components. Isotherms of mixtures of an anionic biosurfactant
      (lichenysin) and a cationic aminoacid surfactant (C3(LA)2) indicate a strong
      interaction suggesting the formation of a new "pseudo-surfactant". The
      antimicrobial properties of the mixture lichenysin and C3(LA)2 M80:20, indicate a
      synergistic effect of the components. The mechanism of action on the bacterial
      envelope was assessed by flow cytometry and Transmission Electron Microscopy.

PMID- 27718396
TI  - Ferritin-supported lipid bilayers for triggering the endothelial cell response.
AB  - Hybrid nanoassemblies of ferritin and silica-supported lipid bilayers (ferritin
      SLBs) have been prepared and tested for the adhesion, spreading and proliferation
      of retinal microvascular endothelial cells (ECs). Lipid membranes with varying
      surface charge were obtained by mixing cationic 1-palmitoyl-2-oleoyl-sn-glycero-3
      ethylphosphocholine (POEPC) with zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) at increasing POPC/POEPC ratios. The supported bilayer
      formation and their subsequent interaction processes with ferritin were studied
      at the pH of 7.4 at different protein concentrations, by using the quartz crystal
      microbalance with dissipation monitoring and by atomic force microscopy. Both
      kinetics and viscoelastic parameters of the protein-lipid membrane interface were
      scrutinized, as well as surface coverage. Phase-contrast optical microscopy
      analyses of the ferritin-SLBs substrates after their interaction with endothelial
      cells evidenced the highest cell adhesion (2-4h of incubation time) and
      proliferation (from 24h to 5 days) for the membranes of POPC/POEPC (75:25 ratio).
      Moreover, ferritin increased both cell adhesion and proliferation in comparison
      to control glass (respectively 1.5- and 1.75-fold) as well as proliferation in
      comparison to bare POPC/POEPC (95:5 ratio) (2 fold). Results are very promising
      in the goal of modulating the endothelial cell response through the interplay of
      viscoelastic/charge properties of the solid-supported membranes and the SLB
      conditioned ferritin activity.

PMID- 27718397
TI  - Removal of nutrients from undiluted anaerobically treated piggery wastewater by
      improved microalgae.
AB  - This study aimed at improving the adaptability and biodegradability of tested
      microalgae in undiluted anaerobic fermentation slurry of piggery wastewater. For
      that, a two-stage method based on UV irradiation followed by gradual
      domestication was developed. The distinctness of this method was the elimination
      of a screening procedure and just needed the UV-irradiated cells with appropriate
      survival to be subjected to gradual domestication. The microalgae treated with
      the method not only grew well in undiluted slurry, but achieved outstanding
      removal efficiencies in total nitrogen (TN) and total phosphorus (TP). Large
      scale application was conducted in an open raceway pond, and the concentrations
      of TN and TP after treatment were 43.80mg/L (removal rate of 89.5%) and 5.83mg/L
      (removal rate of 85.3%) respectively, which greatly excelled the Chinese
      discharge standards for livestock and poultry wastewater. The strategy is
      therefore a promising method for microalgae to purify piggery slurry containing
      high nutrient contents.

PMID- 27718398
TI  - Effect of aeration rate on performance and stability of algal-bacterial symbiosis
      system to treat domestic wastewater in sequencing batch reactors.
AB  - This study investigated aeration rate (0, 0.2, 0.4 and 1.0L/min) effects on algal
      bacterial symbiosis (ABS) and conventional activated sludge (CAS) systems while
      treating domestic wastewater in sequencing batch reactors. Experiment results
      showed that ABS system performed better on NH4+-N, total nitrogen and total
      phosphorus removal than CAS system, especially under lower aeration rate
      condition (0.2Lair/min), with removal efficiencies improvements of 18.90%, 12.45%
      and 46.66%, respectively. The mechanism study demonstrated that a favorable
      aeration rate reduction (half of traditional value in CAS system) could enhance
      algae growth but weaken hydraulic shear force, which contributed to the
      interactions between algae and sludge flocs and further stability of ABS system.
      In addition, algae growth protected both ammonia and nitrite oxidizing bacteria
      from optical damage. It is expected that the present study would provide some new
      insights into ABS system and be helpful for development of low-energy demand
      wastewater treatment process.

PMID- 27718401
TI  - Biodiesel production in crude oil contaminated environment using Chlorella
      vulgaris.
AB  - Biodiesel is a valuable alternative to fossil fuels and many countries choose
      biodiesel as an unconventional energy source. A large number of investigations
      have been done on microalgae as a source of oil production. In recent years,
      wastewater pollutions have caused many ecological problems, and therefore,
      wastewater phycoremediation has attracted the international attention. This paper
      studied the cultivation of Chlorella vulgaris in a crude oil polluted environment
      for biodiesel production. Intended concentrations were 10 and 20gperliter (crude
      oil/water) at two times. The results showed that the growth of C. vulgaris was
      improved in wastewater and the maximum amount of dry mass and oil was produced at
      the highest concentration of crude oil (0.41g and 0.15g/l, respectively). In
      addition, dry mass and oil yield of the microalga were significantly enhanced by
      increasing the experiment duration.

PMID- 27718399
TI  - Excellent N-fixing and P-solubilizing traits in earthworm gut-isolated bacteria:
      A vermicompost based assessment with vegetable market waste and rice straw feed
      mixtures.
AB  - Vermicomposting is a dependable waste recycling technology which greatly augments
      N and P levels mainly through microbial action. This paper aims to identify
      efficient N-fixing (NFB) and P-solubilizing (PSB) bacteria from earthworm
      intestines. Various combinations of vegetable market waste, rice straw, and
      cowdung were fed to two earthworm species (Eisenia fetida and Perionyx
      excavatus). Total organic C decreased, pH shifted towards neutrality, and NPK
      availability, and microbial (NFB, PSB, and total bacteria) population increased
      remarkably during vermicomposting with E. fetida. Therefore, 45 NFB and 34 PSB
      strains isolated from Eisenia gut were initially screened, their inter-dominance
      assessed, and 8 prolific strains were identified through 16SrRNA sequencing.
      Interestingly, two novel N-fixing strains of Kluyvera ascorbata emerged as an
      efficient biofertilizer candidate. Moreover, both N-fixing and P-solubilizing
      strains of Serratia and Bacillus were isolated from earthworm gut. All the
      isolated strains significantly improved soil health and facilitated crop growth
      as compared to commercial biofertilizers.

PMID- 27718400
TI  - Structural elucidation of Eucalyptus lignin and its dynamic changes in the cell
      walls during an integrated process of ionic liquids and successive alkali
      treatments.
AB  - An integrated process based on ionic liquids ([Bmim]Cl and [Bmim]OAc)
      pretreatment and successive alkali post-treatments (0.5, 2.0, and 4.0% NaOH at 90
      degrees C for 2h) was performed to isolate lignins from Eucalyptus. The
      structural features and spatial distribution of lignin in the Eucalyptus cell
      wall were investigated thoroughly. Results revealed that the ionic liquids
      pretreatment promoted the isolation of alkaline lignin from the pretreated
      samples without obvious structural changes. Additionally, the integrated process
      resulted in syringyl-rich lignin macromolecules with more beta-O-4' linkages and
      less phenolic hydroxyl groups. Confocal Raman microscopy analysis showed that the
      dissolution behavior of lignin was varied in the morphologically distinct regions
      during the successive alkali treatments, and lignin dissolved was mainly stemmed
      from the secondary wall regions. These results provided some useful information
      for understanding the mechanisms of delignification during the integrated process
      and enhancing the potential utilizations of lignin in future biorefineries.

PMID- 27718403
TI  - Simultaneous production of proteases and antioxidant compounds from agro
      industrial by-products.
AB  - The use of processes for simultaneous production of bioproducts as enzymes and
      bioactive compounds is an interesting alternative to reduce environmental
      impacts. Thus, the aim of this study was to produce simultaneously, using the
      biorefinery concept, both proteases and bioactive compounds with antioxidant
      activity from Bacillus sp. P45 cultivation by using different by-products. The
      integrated process developed in this study enabled to obtain enzymes with
      proteolytic and keratinolytic properties in a process with alternate substrates
      from agro-industrial by-products (feather meal, residual feather meal and
      biomass), thus, creating an interesting alternative to managing them. The
      residual biomass provided the highest protease activity (1306.6U/mL) and the
      reused feather meal reached the highest keratinolytic activity (89U/mL), both at
      32h of cultivation. Moreover, hydrolysates produced in cultivation using feather
      meal and residual biomass had high antioxidant activity, they have great
      potential as natural antioxidants.

PMID- 27718402
TI  - Biodegradation of petroleum hydrocarbons by oleophilic strain of Pseudomonas
      aeruginosa NCIM 5514.
AB  - The aim of this work was to study the potential of an indigenous strain of
      Pseudomonas aeruginosa NCIM 5514, isolated from petroleum-polluted soil, for the
      biodegradation of crude petroleum oil. The isolate completely decolorized 2,6
      dichlorophenol indophenol in 120h when grown at (37+/-1 degrees C), indicating
      its hydrocarbon utilizing nature. Ex situ biodegradation study was performed to
      find out quantitative utilization and biodegradation of paraffin(s) present in
      crude oil. When the culture was grown in Bushnell-Hass medium containing crude
      oil (3%,v/v) at 37 degrees C, 180rpm for 60days, the viscosity of the oil was
      reduced from 1883cp to 1002cp. Gravimetric and gas chromatographic analysis
      showed 61.03% and 60.63% of biodegradation of C8-C36+ hydrocarbons, respectively.
      These results indicated that the isolate has potential to be used for ex-situ and
      in-situ bioremediation of hydrocarbon pollutants and could have promising
      applications in petrochemical industry.

PMID- 27718404
TI  - Clarification of phosphorus fractions and phosphorus release enhancement
      mechanism related to pH during waste activated sludge treatment.
AB  - This study aimed to clarify phosphorus (P) fractions in waste activated sludge
      (WAS) and explore release performance and enhancement mechanism of different P
      species related to pH. Results showed that inorganic P (IP) was the major P
      fraction in raw sludge (87.86% of total solid P), and non-apatite inorganic P
      (NAIP), the most labile P forms, occupied 81.30% of IP, suggesting that WAS could
      be selected as potential substitution of phosphate rock. The optimized acid and
      alkaline conditions were pH=4 and pH=12 for molybdate reactive P accumulation,
      increased by 311.20mg/L and 479.18mg/L compared to raw sludge, which were 3.80
      and 5.84 times higher than that of control, respectively. The mechanism study
      demonstrated that high pH promoted NAIP release, and apatite P was sensitive to
      low pH. Moreover, the releasable and recoverable P depended on both fractions of
      different P species in sludge and pH adjustment for sludge treatment.

PMID- 27718405
TI  - Electricity generation from macroalgae Enteromorpha prolifera hydrolysates using
      an alkaline fuel cell.
AB  - The goal of this work was to develop a method for the direct power generation
      using macroalgae Enteromorpha prolifera. The process conditions for the
      saccharification of macroalgae were optimized and a type of alkaline fuel cell
      contained no precious metal catalysts was developed. Under optimum conditions
      (170 degrees C and 2% hydrochloric acid for 45min), dilute acid hydrolysis of the
      homogenized plants yielded 272.25g reducing sugar/kg dry algal biomass. The
      maximum power density reached 3.81W/m2 under the condition of 3M KOH and 18.15g/L
      reducing sugar in hydrolysate, higher than any other reported algae-fed fuel
      cells. This study represents the first report on direct electricity generation
      from macroalgae using alkaline fuel cells, suggesting that there is great
      potential for the production of renewable energy using marine biomass.

PMID- 27718406
TI  - Crossing the invisible line: De-differentiation of wake, sleep and dreaming may
      engender both creative insight and psychopathology.
AB  - Writing about dreaming, the poet Raymond Carver said "I feel as if I've crossed
      some kind of invisible line". In creative people, the "line" between wake,
      dreaming and psychopathology may be porous, engendering a de-differentiated,
      super-critical, hybrid state. Evidence exists for a relationship between
      creativity and psychopathology but its nature has been elusive. De
      differentiation between wake, sleep and dreaming may be the common substrate, as
      dream-like cognition pervades wake and wake-like neurophysiology suffuses sleep.
      Chaos theory posits brain states as inherently labile, transient and dynamically
      unstable. Over and above transient dissociations, an enduring and, sometimes,
      progressive, de-differentiation may be possible. Evidence indicates that sleep
      and dreaming facilitate creative insight. In consequence, a mild to moderate form
      of de-differentiation may enhance creativity but if wake-like neurobiology
      permeates sleep this may disrupt sleep-dependent memory processing and emotional
      regulation. If de-differentiation is progressive and enduring, various forms of
      psychopathology may result.

PMID- 27718407
TI  - A template model of embodiment while dreaming: Proposal of a mini-me.
AB  - Dreams are usually centered around a dream self capable of tasks generally
      impossible in waking, e.g. flying or walking through walls. Moreover, the bodily
      dream self appears relatively stable and insensitive to changes of the embodied
      wake self, raising the question of whether and to what extent the dream self is
      embodied. To further explore its determinants, we tested whether the dream self
      would be affected by either pre-sleep focused attention to a body part or by its
      experimental alteration during the day. Choosing a repeated-measures design, we
      analyzed how often key words reflecting the experimental manipulations appeared
      in the dream reports. Results suggest that the dream self is not affected by
      these manipulations, strengthening the hypothesis that, in the majority of
      dreams, the dream self is only weakly embodied, utilizing a standard template of
      embodiment akin to a prototype of self operating independently from the physical
      waking self.

PMID- 27718408
TI  - Flexible thin-layer plasma inactivation of bacteria and mold survival in beef
      jerky packaging and its effects on the meat's physicochemical properties.
AB  - The aims of the present study were to examine the use of a flexible thin-layer
      plasma system in inactivating bacteria and mold on beef jerky in a commercial
      package and to evaluate the physicochemical changes of the jerky. After plasma
      treatment for 10min, Escherichia coli O157:H7, Listeria monocytogenes, Salmonella
      Typhimurium, and Aspergillus flavus populations on the beef jerky were reduced by
      approximately 2 to 3Log CFU/g. No significant changes in metmyoglobin content,
      shear force, and myofibrillar fragmentation index were found in the plasma
      treated beef jerky. On the other hand, the peroxide content and L* value were
      decreased whereas the a* and DeltaE value were increased in the plasma-treated
      sample. Sensory evaluation indicated negative effects of plasma treatment on
      flavor, off-odor, and overall acceptability of the beef jerky. In conclusion, the
      flexible thin-layer plasma system could be employed as a means for
      decontamination of beef jerky, with slight changes to the physicochemical quality
      of the product.

PMID- 27718409
TI  - New phagotrophic euglenoid species (new genus Decastava; Scytomonas saepesedens;
      Entosiphon oblongum), Hsp90 introns, and putative euglenoid Hsp90 pre-mRNA
      insertional editing.
AB  - We describe three new phagotrophic euglenoid species by light microscopy and 18S
      rDNA and Hsp90 sequencing: Scytomonas saepesedens; Decastava edaphica; Entosiphon
      oblongum. We studied Scytomonas and Decastava ultrastructure. Scytomonas
      saepesedens feeds when sessile with actively beating cilium, and has five
      pellicular strips with flush joints and Calycimonas-like microtubule-supported
      cytopharynx. Decastava, sister to Keelungia forming new clade Decastavida on 18S
      rDNA trees, has 10 broad strips with cusp-like joints, not bifurcate ridges like
      Ploeotia and Serpenomonas (phylogenetically and cytologically distinct genera),
      and Serpenomonas-like feeding apparatus (8-9 unreinforced microtubule pairs loop
      from dorsal jaw support to cytostome). Hsp90 and 18S rDNA trees group Scytomonas
      with Petalomonas and show Entosiphon as the earliest euglenoid branch. Basal
      euglenoids have rigid longitudinal strips; derived clade Spirocuta has spiral
      often slideable strips. Decastava Hsp90 genes have introns. Decastava/Entosiphon
      Hsp90 frameshifts imply insertional RNA editing. Petalomonas is too heterogeneous
      in pellicle structure for one genus; we retain Scytomonas (sometimes lumped with
      it) and segregate four former Petalomonas as new genus Biundula with pellicle
      cross section showing 2-8 smooth undulations and typified by Biundula
      (=Petalomonas) sphagnophila comb. n. Our taxon-rich site-heterogeneous rDNA trees
      confirm that Heteronema is excessively heterogeneous; therefore we establish new
      genus Teloprocta for Heteronema scaphurum.

PMID- 27718410
TI  - Interictal irritability and associated factors in epilepsy patients.
AB  - PURPOSE: Irritability has been reported in epilepsy patients. We identified
      associated factors for interictal irritability in epilepsy patients. METHOD:
      Adult epilepsy patients who received antiepileptic drugs (AEDs) for at least
      1year were invited to participate in this study. For eligible patients, several
      questionnaires, such as the Irritability in Adult Patients with Epilepsy (I-Epi),
      the Korean version of the Neurological Disorders Depression Inventory for
      Epilepsy (K-NDDI-E), the Generalized Anxiety Disorder-7 (GAD-7), the Epworth
      Sleepiness Scale (ESS), and the Insomnia Severity Index (ISI), were administered.
      We investigated factors for determining the overall I-Epi score using univariate
      and multivariate analyses. RESULTS: A total of 276 patients with epilepsy were
      included in the study. Mean duration of epilepsy was 15.4 years (2-58 years), and
      146 patients (52.9%) had a seizure freedom for 1year. Mean overall I-Epi score
      was 46.1 (18-105), and 163 patients (59.1%) had at least a moderate level of
      irritability. Although several factors, including demographic, socioeconomic,
      psychosomatic, epilepsy-related factors, and levetiracetam intake, were
      associated with the overall I-Epi score, the strongest factor was the K-NDDI-E
      score, followed by the ISI score, the GAD-7 score, the ESS score, seizure
      control, and duration of epilepsy. CONCLUSION: An appropriate management of
      psychosomatic problems and epileptic attacks is likely to reduce irritability in
      epilepsy patients. Acknowledgment of irritability by clinicians will reduce drug
      failure when they administer AEDs with negative psychotropic profiles, especially
      irritability and aggression.

PMID- 27718412
TI  - Early fluid resuscitation and volume therapy in venoarterial extracorporeal
      membrane oxygenation.
AB  - PURPOSE: For circulatory support, venoarterial extracorporeal membrane
      oxygenation (VA-ECMO) is dependent on sufficient venous drainage ensured by fluid
      therapy. Volume overload however is linked to poor prognosis. This study
      therefore evaluates volume therapy in VA-ECMO. MATERIAL AND METHODS: We report
      data of a single center registry of all patients after VA-ECMO implantation
      treated between 2010 and 2015. RESULTS: A total of 195 patients were included in
      this registry with a medium age of 58.2 +/- 1.1 years, 71.8% were male. A
      positive fluid balance was detected in 94.7% at day 1 (day 2: 93.7%, day 3:
      92.6%). Consistently, survivors had a lower fluid balance when compared to non
      survivors (P < .001). Three hours post-implantation, patients above the 75th
      percentile had a hazard ratio of 6.03 when compared to average survival (P <
      .05). AUC at that time point was 0.726 as calculated by ROC. Patients below the
      50th percentile (fluid balance below 8500 mL after 24 hours) had the best
      prognosis after VA-ECMO implantation (P < .001). CONCLUSIONS: Higher fluid
      balance was consistently linked to poor survival. We found no evidence to support
      a liberal fluid therapy in VA-ECMO patients, especially not the early after
      implantation. With a retrospective study, one cannot clarify if lower fluid
      balance might improve outcomes or represents a prognostic marker.

PMID- 27718411
TI  - Hematologic counts as predictors of delayed cerebral ischemia after aneurysmal
      subarachnoid hemorrhage.
AB  - PURPOSE: Aneurysmal subarachnoid hemorrhage (SAH) is associated with high
      morbidity and mortality, but currently no single clinical method or ancillary
      test can reliably predict which subset of patients will develop delayed cerebral
      ischemia (DCI). The aim of this study was to find hematologic derangements and
      clinical factors present during the first 7 days after bleeding that could help
      identify patients at risk for development of DCI. MATERIALS AND METHODS: Databank
      analysis of patients with SAH admitted between 2010 and 2012 in a single center.
      Data from demographics, imaging, laboratory, and clinical factors were collected.
      Statistical testing was conducted to test for association to the outcome, and
      multivariate logistic regression was used to design a predictive model. RESULTS:
      Of 55 patients, 14 developed DCI (25%). Anemia and leukocytosis on the third day
      after bleeding were significantly correlated with the outcome (for anemia:
      P<.032; confidence interval, 1.12-15.16; odds ratio, 4.12; for leukocytosis:
      P<.046; confidence interval, 1.03-26.13; odds ratio, 5.18). Anemia and
      leukocytosis were still statistically significant after adjustment for age, sex,
      modified Fisher scale, and Hunt-Hess scale. CONCLUSION: The presence of
      leukocytosis and anemia during the third day after SAH was statistically
      correlated with the occurrence of DCI.

PMID- 27718413
TI  - Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial
      evaluation, toxicological studies, and target exploration.
AB  - Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure
      activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in
      silico metabolism, in silico pharmacophore modeling, and in vivo studies led to
      the identification of compounds 22 and 23 with significant in vitro
      antiplasmodial activity against drug sensitive (D6 IC50 <= 0.19 MUM) and
      multidrug resistant (FCR-3 IC50 <= 0.40 MUM and C235 IC50 <= 0.28 MUM) strains of
      Plasmodium falciparum. Adequate selectivity index and absence of genotoxicity was
      also observed. Notably, compound 22 displays excellent parasitemia reduction (98
      +/- 1%), and complete cure with all treated mice surviving through the entire
      period with no signs of toxicity. One important factor is the agreement between
      in vitro potency and in vivo studies. Target exploration was performed; this
      chemotype series exhibits an alternative antimalarial mechanism.

PMID- 27718415
TI  - Cross section measurement of alpha particle induced nuclear reactions on natural
      cadmium up to 52MeV.
AB  - Cross sections of alpha particle induced nuclear reactions have been measured on
      thin natural cadmium targets foils in the energy range from 11 to 51.2MeV. This
      work was a part of our systematic study on excitation functions of light ion
      induced nuclear reactions on different target materials. Regarding the cross
      sections, the alpha induced reactions are not deeply enough investigated. Some of
      the produced isotopes are of medical interest, others have application in
      research and industry. The radioisotope 117mSn is a very important theranostic
      (therapeutic + diagnostic) radioisotope, so special care was taken to the results
      for that isotope. The well-established stacked foil technique followed by gamma
      spectrometry with HPGe gamma spectrometers were used. The target and monitor
      foils in the stack were commercial high purity metal foils. From the irradiated
      targets 117mSn, 113Sn, 110Sn, 117m,gIn, 116mIn, 115mIn, 114mIn, 113mIn, 111In,
      110m,gIn, 109mIn, 108m,gIn, 115gCd and 111mCd were identified and their
      excitation functions were derived. The results were compared with the data of the
      previous measurements from the literature and with the results of the theoretical
      nuclear reaction model code calculations TALYS 1.8 (TENDL-2015) and EMPIRE 3.2
      (Malta). From the cross section curves thick target yields were calculated and
      compared with the available literature data.

PMID- 27718414
TI  - Reductions in experiential avoidance as a mediator of change in symptom outcome
      and quality of life in acceptance-based behavior therapy and applied relaxation
      for generalized anxiety disorder.
AB  - As a field, we lack information about specific mechanisms that are responsible
      for changes that occur over the course of treatments for anxiety disorders
      (Kazdin, 2007). Identifying these mechanisms would help streamline evidence-based
      approaches, increase treatment response rates, and aid in the dissemination and
      implementation of evidence-based approaches in diverse contexts. The current
      study examined reductions in experiential avoidance (EA; Hayes, Wilson, Gifford,
      Follette, & Strosahl, 1996), attempts to control or eliminate distressing
      internal experiences, regardless of behavioral consequences, as a potential
      mechanism of change in participants with a principal diagnosis of generalized
      anxiety disorder (GAD) receiving either acceptance-based behavior therapy (ABBT)
      or applied relaxation (AR). Participants' EA scores across treatment on the
      Acceptance and Action Questionnaire (AAQ) were used to calculate slopes, which
      were used as predictors in a series of linear regressions. Greater change in EA
      across treatment significantly predicted change in worry (PSWQ) and quality of
      life (QOLI) across both treatments. These results contribute to the body of
      literature on common mechanisms of change across traditional CBTs and mindfulness
      and acceptance-based approaches.

PMID- 27718416
TI  - When pathological and radiological correlation is achieved, excision of
      fibroadenoma with lobular neoplasia on core biopsy is not warranted.
AB  - BACKGROUND: The diagnosis and management of lobular neoplasia (LN) including
      lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) remains
      controversial. Current management options after a core needle biopsy (CNB) with
      lobular neoplasia (LN) incorporating both ALH and LCIS include excision biopsy or
      careful clinical and radiologic follow up. METHODS: A retrospective analysis of
      the surgical database at Cork University Hospital was performed to identify all
      core needle biopsies from January 1st 2010 to 31st December 2013 with a diagnosis
      of FA who subsequently underwent surgical excision biopsy. All cases with
      associated LN including ALH and classical LCIS were selected. We excluded cases
      with coexistent ductal carcinoma in situ (DCIS), invasive carcinoma, LN
      associated with necrosis, pleomorphic lobular carcinoma in situ (PLCIS) or
      lesions which would require excision in their own right (papilloma, radial scar,
      atypical ductal hyperplasia (ADH) or flat epithelial atypia (FEA)). Cases in
      which the radiologic targeted mass was discordant with a diagnosis of FA were
      also excluded. RESULTS: 2878 consecutive CNB with a diagnosis of FA were
      identified. 25 cases had a diagnosis of concomitant ALH or classical LCIS. Our
      study cohort consisted of 21 women with a mean age 53 years (age range 41-70
      years). The core biopsy diagnosis was of LCIS and FA in 16 cases and ALH and FA
      in 5 cases. On excision biopsy, a FA was confirmed in all 21 cases. In addition
      to the FA, residual LCIS was present in 14 cases with residual ALH in 2 cases.
      One of the twenty-one cases (4.8%) was upgraded to invasive ductal carcinoma on
      excision.

PMID- 27718417
TI  - Initial experience of automated breast volume scanning (ABVS) and ultrasound
      elastography in predicting breast cancer subtypes and staging.
AB  - OBJECTIVES: Breast cancer is a heterogeneous disease consisting of distinct
      histopathological subtypes with different clinical outcomes. In this article, we
      identified the automated breast volume scanning (ABVS) and shear wave velocity
      (SWV) characteristics of different pathological types of breast carcinoma.
      METHODS: A retrospective review of both ABVS and SWV imaging of 118 consecutive
      breast masses was performed. The imaging features of both techniques were
      assessed with reference to histopathological results. RESULTS: Echo heterogeneity
      with a smooth and lobulated margin was a significant feature more frequently
      found in mucinous carcinoma groups (100%, P < 0.05). Between different stages of
      ductal carcinoma, echo homogeneity was more likely in high-grade ductal
      carcinomas (P < 0.05). SWV differences existed between inside tumor areas and
      either tumor boundary or tissues outside the tumors (P < 0.05), and values
      differed between different breast carcinoma stages. The central and tumor margin
      areas of ductal carcinomas were much harder than in tubular carcinoma and micro
      carcinoma, respectively (P < 0.05). SWV ROC curve analyses yielded a cut-off
      value of 3.015 m/s between ductal carcinoma in situ (DCIS) and invasive ductal
      carcinoma in the central part of lesions, with 83.5% sensitivity and 80%
      specificity for T0 vs T1-3 staging. CONCLUSIONS: Since some features were
      associated with different breast carcinoma types and stages, ABVS and SWV imaging
      has the potential to give clues about breast carcinoma differentiation in a non
      invasive manner.

PMID- 27718418
TI  - Comparative effects of Ni(II) and Cu(II) ions and their combinations on redox
      potential and hydrogen photoproduction by Rhodobacter sphaeroides.
AB  - The aim of the present work was the study of comparative effects of Cu(II) and
      Ni(II) and their mixture on growth, redox potential, hydrogen (H2) yield and
      ATPase activity in phototrophic purple bacteria R. sphaeroides MDC6522 from
      Jermuk mineral spring in Armenia. It was ascertained, that Cu2+ and Ni2+ have
      different effects on bacterial specific growth rate: in the presence of 5MUM Cu2+
      growth rate was ~3.2-fold lower in comparison with control (no addition), and
      increased ~1.5-fold in medium with 5MUM Ni2+. These changes may be resulted by
      action of the ions on redox potential (Eh). Low concentrations of Ni2+ had an
      enhancing effect on the Eh drop and H2 production. The increase of concentration
      from 1 to 5MUM enhanced the stimulatory effect of Ni2+. H2 yield in R.
      sphaeroides (72h of growth) was enhanced ~3-fold with 5MUM Ni2+, whereas in the
      presence of 5MUM Cu2+ H2 yield was ~1.2 fold lower in comparison with control.
      Cu2++Ni2+ combinations effects were differed from the effect when ions used
      separately. When Cu2+ and Ni2+ were added together, the Ni2+ stimulatory effect
      disappeared, which indicated that heavy metal ions mixture may have different
      action mechanisms. Moreover, N,N'-dicyclohexylcarbodiimide-sensitive ATPase
      activity of R. sphaeroides membrane vesicles has been increased in the presence
      of both ions, but in the presence of Su2+ the influence was feebly marked in
      comparison with Ni2+. The results suggest an interaction between these ions and
      the FOF1-ATPase. Thus, the results obtained point out discrimination between Cu2+
      and Ni2+ and their combinations effects and reveal new regulatory pathways to
      enhance H2 yield in R. sphaeroides.

PMID- 27718419
TI  - Spectroscopic characterization of the effect of mouse twinfilin-1 on actin
      filaments at different pH values.
AB  - The effect of mammalian twinfilin-1 on the structure and dynamics of actin
      filaments were studied with steady state fluorescence spectroscopy, total
      internal reflection fluorescence microscopy and differential scanning calorimetry
      techniques. It was proved before that the eukaryotic budding yeast twinfilin-1
      can efficiently bind and severe actin filaments in vitro at low pH values. In the
      present work steady-state anisotropy measurements revealed that twinfilin can
      bind efficiently to F-actin. Dilution-induced depolymerization assay proved that
      mammalian twinfilin-1 has an actin filament severing activity. This severing
      activity was more pronounced at low pH values. Total internal reflection
      fluorescence microscopy measurements could support the severing activity of mouse
      twinfilin-1. The average rate of depolymerization was more apparent at low pH
      values. The differential scanning calorimetry measurements demonstrated that
      mammalian twinfilin-1 could reduce the stiffness within the actin filaments
      before the detachment of the actin protomers. The structural and dynamic
      reorganization of actin can support the twinfilin-1 induced separation of actin
      protomers. The measured data indicated that mammalian twinfilin-1 was able to
      accelerate the monomers dissociation and/or sever the filaments effectively at
      low pH values. It was concluded that twinfilin-1 can affect the F-actin in
      biological processes or under stress situations when the pH is markedly under the
      physiological level.

PMID- 27718420
TI  - Near-infrared laser increases MDPC-23 odontoblast-like cells proliferation by
      activating redox sensitive pathways.
AB  - Near infrared laser is known to induce biostimulatory effects, resulting in cell
      proliferation enhancement. Although such positive effect is widely exploited in
      various clinical applications, molecular mechanisms involved are still poorly
      understood. The aim of the study was to investigate the ability of laser
      stimulation to increase cell proliferation through an early activation of three
      redox sensitive pathways, namely Nrf-2, NF-kappaB and ERK in a rat odontoblast
      like cell line (MDPC-23 cells). MDPC-23 cells were irradiated with different
      energy settings (0-50J, corresponding to 0-32.47J/cm2) and cell proliferation was
      evaluated by cell counting. Nrf-2, NF-kappaB and ERK signaling pathways
      activation was investigated through Western blot analysis. Our results show that
      a single 25J laser stimulation is able to increase cell proliferation and that
      this effect could be increased by repeating the stimulation twice with a time
      lapse of 24h. Western blot experiments demonstrated that laser stimulation is
      able to induce an early activation response in intracellular signaling, with an
      overlapping time pattern between the three considered pathways. Results discussed
      in this paper reveal a complex mechanism underlying near-infrared induced
      increase in pre-odontoblasts proliferation, involving three survival pathways
      that can act both separately or through reciprocal crosstalk. In particular, data
      presented suggest an important role for ERK pathway that could act directly by
      stimulating cell proliferation but can also induce both Nrf-2 and NF-kappaB
      activation, acting as a critical cellular checkpoint in response to imbalanced
      redox state generated by a laser induced increase in ROS production.

PMID- 27718421
TI  - DNA damage protecting and free radical scavenging properties of mycosporine-2
      glycine from the Dead Sea cyanobacterium in A375 human melanoma cell lines.
AB  - Mycosporine-like amino acids (MAAs) are a group of natural sunscreen compounds
      that possess highly photoprotective properties. The most commonly found MAAs in
      marine organisms is shinorine, porphyra-334, and mycosporine-glycine. However,
      the halophilic species accumulate mycosporine-2-glycine (M2G) as the major MAA.
      In this study, we have investigated the protective effect of M2G against
      oxidative stress. In vitro radical scavenging activity revealed that M2G
      exhibited a significant inhibition with scavenging concentration (SC) 50 value of
      22+/-1.4MUM. In vivo analysis using the human melanoma A375 and a control cell
      line (NHSF) showed that M2G at low concentration (i.e. micromolar range)
      protected the cells against the oxidative stress (H2O2)-induced cell death. Comet
      assay to assess total DNA strand breaks demonstrated that M2G was not genotoxic
      and protected against the DNA damage by H2O2 treatment at the same level as
      ascorbic acid. To our knowledge, this is the first evidence demonstrating
      potential protective role of the natural sunscreen compound M2G against oxidative
      stress-induced DNA damage in human cell lines. The potent antioxidant activity
      combined with DNA protection ability of M2G may support its endorsement as a
      potential natural sunscreen with antioxidant property. These findings provide
      important clues for possible use of M2G in pharmaceutical and biotechnological
      applications.

PMID- 27718422
TI  - Low episodic memory performance in cognitively normal elderly subjects is
      associated with increased posterior cingulate gray matter N-acetylaspartate: a 1H
      MRSI study at 7 Tesla.
AB  - Low episodic memory performance characterizes elderly subjects at increased risk
      for Alzheimer's disease (AD) and may reflect neuronal dysfunction within the
      posterior cingulate cortex and precuneus (PCP) region. To investigate a potential
      association between cerebral neurometabolism and low episodic memory in the
      absence of cognitive impairment, tissue-specific magnetic resonance spectroscopic
      imaging at ultrahigh field strength of 7 Tesla was used to investigate the PCP
      region in a healthy elderly study population (n = 30, age 70 +/- 5.7 years, Mini
      Mental State Examination 29.4 +/- 4.1). The Verbal Learning and Memory Test
      (VLMT) was administered as part of a neuropsychological battery for assessment of
      episodic memory performance. Significant differences between PCP gray and white
      matter could be observed for glutamate-glutamine (p = 0.001), choline (p = 0.01),
      and myo-inositol (p = 0.02). Low Verbal Learning and Memory Test performance was
      associated with high N-acetylaspartate in PCP gray matter (p = 0.01) but not in
      PCP white matter. Our data suggest that subtle decreases in episodic memory
      performance in the elderly may be associated with increased levels of N
      acetylaspartate as a reflection of increased mitochondrial energy capacity in PCP
      gray matter.

PMID- 27718423
TI  - Fine-mapping the effects of Alzheimer's disease risk loci on brain morphology.
AB  - The neural substrate of genetic risk variants for Alzheimer's disease (AD)
      remains unknown. We studied their effect on healthy brain morphology to provide
      insight into disease etiology in the preclinical phase. We included 4071
      nondemented, elderly participants of the population-based Rotterdam Study who
      underwent brain magnetic resonance imaging and genotyping. We performed voxel
      based morphometry (VBM) on all gray-matter voxels for 19 previously identified,
      common AD risk variants. Whole-brain expression data from the Allen Human Brain
      Atlas was used to examine spatial overlap between VBM association results and
      expression of genes in AD risk loci regions. Brain regions most significantly
      associated with AD risk variants were the left postcentral gyrus with ABCA7
      (rs4147929, p = 4.45 * 10-6), right superior frontal gyrus by ZCWPW1 (rs1476679,
      p = 5.12 * 10-6), and right postcentral gyrus by APOE (p = 6.91 * 10-6). Although
      no individual voxel passed multiple-testing correction, we found significant
      spatial overlap between the effects of AD risk loci on VBM and the expression of
      genes (MEF2C, CLU, and SLC24A4) in the Allen Brain Atlas. Results are available
      online on www.imagene.nl/ADSNPs/. In this single largest imaging genetics data
      set worldwide, we found that AD risk loci affect cortical gray matter in several
      brain regions known to be involved in AD, as well as regions that have not been
      implicated before.

PMID- 27718424
TI  - Anxiety and autonomic response to social-affective stimuli in individuals with
      Williams syndrome.
AB  - BACKGROUND: Williams syndrome (WS) is a genetic condition characterized by an
      unusual "hypersocial" personality juxtaposed by high anxiety. Recent evidence
      suggests that autonomic reactivity to affective face stimuli is disorganised in
      WS, which may contribute to emotion dysregulation and/or social disinhibition.
      METHODS: Electrodermal activity (EDA) and mean interbeat interval (IBI) of 25
      participants with WS (19 - 57 years old) and 16 typically developing (TD; 17-43
      years old) adults were measured during a passive presentation of affective face
      and voice stimuli. The Beck Anxiety Inventory was administered to examine
      associations between autonomic reactivity to social-affective stimuli and anxiety
      symptomatology. RESULTS: The WS group was characterized by higher overall anxiety
      symptomatology, and poorer anger recognition in social visual and aural stimuli
      relative to the TD group. No between-group differences emerged in autonomic
      response patterns. Notably, for participants with WS, increased anxiety was
      uniquely associated with diminished arousal to angry faces and voices. In
      contrast, for the TD group, no associations emerged between anxiety and
      physiological responsivity to social-emotional stimuli. CONCLUSIONS: The anxiety
      associated with WS appears to be intimately related to reduced autonomic arousal
      to angry social stimuli, which may also be linked to the characteristic social
      disinhibition.

PMID- 27718425
TI  - Bacterial disinfection in a sunlight/visible-light-driven photocatalytic reactor
      by recyclable natural magnetic sphalerite.
AB  - A 5-L reactor was designed and used to enhance the sunlight/visible-light-driven
      (VLD) photocatalytic disinfection efficiency towards Gram-negative bacterium
      (Escherichia coli). Natural magnetic sphalerite (NMS) was used as the
      photocatalyst, which could be easily recycled by applying a magnetic field.
      Results showed that NMS with irradiation by the blue light emitting diode (LED)
      lamp could completely inactivate 1.5 * 105 cfu/mL of E. coli within 120 min in
      the first three runs. However, the inactivation efficiency of E. coli started to
      decrease in the 4th Run, while in the 5th run, the E. coli with the initial
      concentration of 5 logs was inactivated to 3.3 (blue-light) and 3.5 logs
      (sunlight), respectively. Moreover, the stability and deactivation mechanism of
      NMS during subsequent runs were also studied. The results showed that the decline
      of the photocatalytic activity was possibly attributed to adsorption of the
      bacterial decomposed compounds on the active sites. In addition, photocatalytic
      bactericidal mechanism of the NMS in the photocatalytic system was investigated
      by using multiple scavengers to remove the specific reactive species. Moreover,
      various Gram-positive bacteria including Staphylococcus aureus, Microbacterium
      barkeri, and Bacillus subtilis could also be efficiently inactivated in the
      photocatalytic system.

PMID- 27718426
TI  - Hair chemical element contents and influence factors of reproductive-age women in
      the West Ujimqin Banner, Inner Mongolia, China.
AB  - Women have an increased risk for chemical element deficiencies during
      reproductive age, particularly due to higher chemical element requirements and
      poor diets. Twenty-one chemical elements (Al, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg,
      Mn, Mo, Ni, Pb, Se, Si, Sn, Sr, Ti, V and Zn) in hair samples, which were
      collected from 71 non-pregnant and 236 pregnant women living in the West Ujimqin
      Banner, central Inner Mongolia, China, were measured, and the environment,
      dietary habits and ethnic group influence factors associated with the biomarker
      were analyzed. The results indicated that the average values of the chemical
      element contents from hair were greatly different compared to those from other
      areas, especially the Al, Cd, Pb, Ca and Sr contents. There was no significant
      difference among the three ethnicities for any element except Mn and Ti in non
      pregnant women. Compared to non-pregnant women, in the first trimester group, the
      levels of nine chemical elements (Ba, Cd, Cu, Pb, Se, Si, Sn and Ti) decreased,
      while the others increased, and the contents of all of the chemical elements
      decreased in the second trimester group, while in the third trimester, there was
      a slight increase. Three chemical elements (Cu, Mn and Zn) displayed a
      synergistic correlation between each other in the third trimester group, which
      may protect the placenta from some oxidant damage. The high levels of Cd and Pb
      in hair likely originate from house renovations and traffic pollution. This study
      provided basic and useful information on the levels of chemical elements in
      reproductive-age women, and the results of this study are helpful to control the
      contents and improve the health of pregnant and non-pregnant women.

PMID- 27718427
TI  - Accumulation and developmental toxicity of hexabromocyclododecanes (HBCDs) on the
      marine copepod Tigriopus japonicus.
AB  - The brominated flame retardants hexabromocyclododecanes (HBCDs) are ubiquitous
      environmental contaminants, widely distributed in aquatic systems including the
      marine environment and marine organisms. HBCDs are toxic to the development of
      both freshwater and marine fish. However, the impacts of HBCDs on marine
      invertebrates are not well known. In this study, the marine copepod, Tigriopus
      japonicus, was used to assess the bioaccumulation and developmental toxicity of
      technical HBCD (tHBCD) through water-borne exposure. The uptake rate constant of
      tHBCD by T. japonicus was high, which resulted in high bioaccumulation potential.
      The bioconcentration factors of tHBCD were 8.73 * 104 and 6.34 * 104 L kg-1 in T.
      japonicus, calculated using the kinetic and steady-state methods, respectively.
      Exposure of T. japonicus nauplii to tHBCD caused significant growth delay. The
      lowest-observable-effect-concentrations of tHBCD induced developmental delay were
      30 and 8 MUg L-1 for the F0 and F1 generations, respectively, which suggested
      that the F1 generation was more sensitive to tHBCD than the F0 generation and
      warranted multiple-generation toxicity tests for future studies. Furthermore,
      exposure of the adult copepods to tHBCD induced the transcription of oxidative
      stress response genes and apoptotic genes, e.g., SOD,CAT, GST, OGG1, P53 and
      Caspase-3. It was therefore speculated that tHBCD exposure induced the generation
      of reactive oxygen species in T. japonicus, which activated the oxidative stress
      defense genes and meanwhile resulted in oxidative DNA damage. The damaged DNA
      activated the transcription of p53 and triggered the caspase-mediated apoptosis
      pathway, which may be the reason for the tHBCD induced developmental delay in T.
      japonicus nauplii.

PMID- 27718428
TI  - Zero-valent iron for the abatement of arsenate and selenate from flowback water
      of hydraulic fracturing.
AB  - Zero-valent iron (ZVI) was tested for the removal of 150 MUg L-1 As(V) and 350
      MUg L-1 Se(VI) in high-salinity (ionic strength 0.35-4.10 M) flowback water of
      hydraulic fracturing. Over 90% As(V) and Se(VI) was removed by 2.5 g L-1 ZVI in
      Day-14 flowback water up to 96-h reaction, with the remaining concentration below
      the maximum contaminant level for As(V) and criterion continuous concentration
      for Se(VI) recommended by US EPA. The kinetics of As(V) and Se(VI) removal
      followed a pseudo-second-order rate expression with the observed rates of 4.51 *
      10-2-4.91 * 10-1 and 3.48 * 10-2-6.58 * 10-1 h-1 (with 0.5-10 g L-1 ZVI),
      respectively. The results showed that Se(VI) removal significantly decreased with
      increasing ionic strength, while As(V) removal showed little variation. Common
      competing anions (nitrate, bicarbonate, silicate, and phosphate), present in
      shallow groundwater and stormwater, caused marginal Se(VI) desorption (2.42 +/-
      0.13%) and undetectable As(V) desorption from ZVI. The competition between As(V)
      and Se(VI) for ZVI removal depended on the initial molar ratio and surface sites,
      which occurred when the Se(VI) concentration was higher than the As(V)
      concentration in this study. The characterization of As(V)- and Se(VI)-loaded ZVI
      by X-ray diffraction and Raman analysis revealed that ZVI gradually converted to
      magnetite/maghemite corrosion products with lepidocrocite in flowback water over
      30 days. Similar corrosion compositions were confirmed in aerobic and anaerobic
      conditions regardless of the molar ratio of As(V) to Se(VI). The high reactivity
      and stability of ZVI showed its suitability for in-situ prevention of As(V) and
      Se(VI) migration due to accidental leakage, spillage, or overflow of flowback
      water.

PMID- 27718429
TI  - The role of Cu(II) in the reduction of N-nitrosodimethylamine with iron and zinc.
AB  - The role of Cu(II) in the reduction of N-nitrosodimethylamine (NDMA) with zero
      valent metals was investigated by determining the effects of Cu(II) on the
      removal, kinetics, products, and mechanism. NDMA removal was enhanced, and all
      reactions followed a pseudo-first-order kinetic model except for the Fe and
      Fe/0.1 mM Cu(II) systems. The iron mass-normalized pseudo-first-order rate
      constants (kMFe) increased with the Cu(II) concentration. The zinc mass
      normalized pseudo-first-order rate constants (kMZn) were identical to those with
      the Cu(II) concentrations from 0.1 mM to 1.0 mM and were higher with 2.0 mM
      Cu(II). The types of products detected were unchanged. Some unknown products were
      also found. NDMA was reduced to 1,1-dimethylhydrazine (unsymmetrical
      dimethylhydrazine, UDMH). Then, UDMH was reduced into dimethylamine (DMA) by the
      Fe/Cu(II) and Zn/Cu(II) systems. Catalytic hydrogenation was proposed as the
      reduction mechanism. Several copper species, such as Cu(OH)2 in the Fe/Cu(II)
      system and Cu2O and Cu(OH)2 in the Zn/Cu(II) system enhanced NDMA reduction.
      Differences between the Fe/Cu(II) and Zn/Cu(II) systems were caused by the
      reduction potentials and surface conditions of the different metals and the
      copper species in the various systems.

PMID- 27718430
TI  - Alkyl bicarbamates supramolecular organogelators with effective selective
      gelation and high oil recovery from oil/water mixtures.
AB  - A series of alkyl bicarbamates supramolecular organogelators were synthesized
      with different structures and lengths of alkyl chains. The driving forces for the
      self-assembly of small molecules, including the intermolecular H bonding, pi-pi
      stacking and van der Waals interactions, played an important role in the
      formation of different 3D network structures, i.e., fibers, ribbons, sheets, and
      prisms. And a probable formation process of the gel networks was proposed.
      Furthermore, the phase-selective gelling performances were investigated for oil
      removal from aqueous solution. Interestingly, the gelling properties were found
      to be affected by the length and structure of alkyl chains, while some gelators
      with intermediate alkyl chain lengths could effectively gel all the tested oils
      from water surface within 15 min, such as Russian crude oil, diesel, gasoline,
      soybean oil, peanut oil, olive oil, cyclohexane, hexane and ethyl acetate.
      Advantageously, fast gelation, high rate of oil removal (>95%) and excellent oil
      retention rate (close to 100%) were realized in the recovery of oil spills from
      water surface. This kind of supramolecular gelators demonstrates good potential
      applications in the delivery or removal of organic pollution from oil/water
      mixtures.

PMID- 27718431
TI  - IL-2 and polyoma BK virus infection; A systematic review article.
AB  - It has been demonstrated that IL-2 plays a dual role in induction/suppression of
      immune responses via activation of conventional and regulatory T lymphocytes,
      respectively. IL-2 contacts complete IL-2 receptor (IL-2R) which contains CD25
      (alpha chain) on the antigen specific activated T helper and cytotoxic
      lymphocytes and also T regulatory cells. Additionally, previous investigations
      revealed that polyoma BK virus (PBK) reactivation and induction of PBK associated
      nephropathy (PBKAN) is a main complication following renal transplantation. Based
      on the important dual roles played by IL-2 in the immune responses, it may be
      hypothesized that IL-2/IL-2R interaction could be considered a potential
      mechanism against/toward PBK reactivation and also PBKAN. Accordingly, the aim of
      the current review article is to determine the roles of IL-2 IL-2/IL-2R
      interaction in PBK reactivation and PBKAN complications.

PMID- 27718432
TI  - Sarcomatoid carcinoma of the jejunum with gastric metastases: A case report and
      review of the literature.
AB  - INTRODUCTION: Sarcomatoid carcinoma (SCA) of jejunum is an extremely rare
      condition. To our knowledge, only 17 cases have been reported in the literature.
      PRESENTATION: We introduced an additional case of the sarcomatoid carcinoma of
      jejunum in a 62-year-old Chinese male who presented with epigastric pain for 3
      weeks. Multiple tumors originated in the jejunum and metastases to mesentery
      lymph nodes and distal stomach were found during the laparotomy. The patient
      underwent palliative resection of the tumors. He died 11 days after the
      operation. DISCUSSION: Sarcomatoid carcinoma (SCA) of jejunum is an extremely
      poor prognostic tumor in human being. The diagnosis of SCA was based on
      pathological observations and immunohistochemical staining. There is no official
      treatment guideline for SCA, but wide excision including the tumor is the main
      goal of treatment. CONCLUSION: This is the first case of sarcomatoid carcinoma of
      jejunum with gastric metastases being reported and also the shortest survival
      period after the operation. Surgery is the cornerstones of treatment but the
      ideal means is still unknown due to the short survival and inadequate reports.

PMID- 27718433
TI  - Liver Angiosarcoma: Rare tumour associated with a poor prognosis, literature
      review and case report.
AB  - INTRODUCTION: Liver angiosarcoma is a very uncommon tumour of mesenchymal origin,
      representing between 0.1-2% of all primary tumours of the liver, affecting mainly
      men in their sixth or seventh decade of life, with a high mortality in the first
      years (Chaudhary et al., 2015). Literature reports of its surgical treatment vary
      from a total or partial hepatectomy with or without liver transplant.
      PRESENTATION OF CASE: A 37year old male, with a 7year history of a fatty liver,
      was found to have a 12cm diameter tumour in a cirrhotic liver, during an
      abdominal Computed Tomography (CT) scan. Patient was asymptomatic with negative
      tumour markers, yet tumour liver biopsy revealed a Liver Angiosarcoma with
      positive immunohistochemistry for neoplastic cells CD31 and CD34. Patient was
      deemed candidate for a partial hepatectomy of the affected liver segments which
      was done without complications and no evidence of other tumour lesions was found
      during surgery. Patient continued oncologic management with ongoing chemotherapy.
      DISCUSION: Liver Angiosarcoma, although rare, persists with a high mortality due
      to its aggressive nature. Never the less liver transplantation, although proven
      to be an effective treatment for many pathologies that culminate in liver
      failure, fails to improve patients' survival and prognosis, when compared to
      partial hepatectomy as surgical management to for liver Angiosarcoma, CONCLUSION:
      Partial hepatectomy as surgical management, followed by adjuvant therapy, for
      Liver Angiosarcoma continues to prove favourable results and prognosis compared
      to Liver Transplantation.

PMID- 27718434
TI  - Laparoscopic totally extra-peritoneal hernia repair for bilateral Spigelian
      hernias and coincident inguinal hernia: A case report.
AB  - INTRODUCTION: Spigelian hernia (SH) is a rare ventral hernia occurring near the
      lateral border of the rectus muscle. The treatment remains controversial and
      depends on institutional expertise. Although laparoscopic surgery is a good
      adaptation for the repair of ventral hernias, only a few cases have been reported
      in the literature. Here, we report a case of totally extra-peritoneal (TEP)
      repair for bilateral SHs. PRESENTATION OF CASE: A 74-year-old Japanese man
      presented with asymptomatic bulges in the right lower abdominal quadrant. On
      physical examination, the bulges were located to the right of the lateral border
      of the abdominal rectus muscle and the right inguinal region in an upright
      position. We diagnosed right SH and coincident homonymous ipsilateral inguinal
      hernia (IH) by abdominal computed tomography and planned a curative operation by
      laparoscopy. By first laparoscopic exploration, we found an asymptomatic SH to
      the left of the lateral border of the abdominal rectus muscle and performed TEP
      repair for all hernias. The second laparoscopic exploration after fixing the mesh
      in place revealed that the orifice of the right SH was scarred and stiffened by
      repeated prolapse. We finally eliminated the sac by ligation because of a fear
      causing of reduction en masse of the SH. DISCUSSION AND CONCLUSION: The use of
      laparoscopy simplified the diagnosis and facilitates the subsequent repair of the
      hernia. TEP approach is the ideal treatment for the simultaneous laparoscopic
      repair of SH and IH.

PMID- 27718435
TI  - Suspected total spinal in patient having emergent Caesarean section, a case
      report and literature review.
AB  - INTRODUCTION: Epidural analgesia is commonly used for management of pain during
      childbirth. Need for emergent Caesarean section e.g. because of signs of foetal
      distress or lack of progress is however not an uncommon event. In females having
      an established epidural; general anaesthesia, top-up of the epidural or putting a
      spinal are all possible options. Dosing of the spinal anaesthesia in females
      having epidural is a matter of discussion. PRESENTATION OF CASE: We describe a
      healthy 32 years, 0 para mother in gestation week 36 having labour epidural
      analgesia but due to foetal distress scheduled for an emergent Caesarean section
      category 2 that developed upper extremity weakness and respiratory depression
      after administration of standard dose high density bupivacaine/morphine/fentanyl
      intrathecal anaesthesia. She was emergent intubated and resumed motor function
      after 15-20min. DISCUSSION: A too extensive cephalic spread was the most
      plausible explanation to the event. Whether or not reducing the dose for a spinal
      anaesthesia in mothers having an established labour epidural analgesia is a
      matter of discussion. It is of course of importance to achieve a rapid and
      effective surgical anaesthesia but also avoiding overdosing with the risk for a
      too high cephalic spread. CONCLUIOSN: To perform spinal anaesthesia for emergent
      Caesarean in patients having an epidural for labour pain is a feasible option and
      should be considered in category 2-3 section. The dose for a convert spinal block
      should be assessed on an individual basis and reasonably reduced.

PMID- 27718436
TI  - Management of aggressive giant cell tumor of calcaneal bone: A case report.
AB  - INTRODUCTION: Prevalence of giant cell tumor (GCT) at atypical locations like
      bones of the feet are rare, seen in <1% of cases. GCT may have aggressive
      features, including cortical expansion or destruction with a soft-tissue
      component. Difficult diagnosis most often followed with complicated management
      and high recurrence rate remains a challenge that is rarely reported.
      PRESENTATION OF CASE: We presented a case of forty-six-year-old male patient with
      giant cell tumor of the right calcaneus Campanacci 3 with secondary aneurysmal
      bone cyst (ABC). Wide excision total calcaneoctomy, followed by reconstruction
      bone defect using femoral head allograft and soft tissue coverage with sural flap
      had been done. DISCUSSION: Conservative surgery with careful curettage and
      placement of bone cement should be considered the treatment of choice when
      feasible. However, aggressive GCTs may require wide excision and reconstruction
      or may be amputation. We decided to do salvage surgery since: traditionally
      curettage is not possible, adequately wide resection of local tumor could be
      achieved, neurovascular bundle was not involved, and also bone and soft tissue
      reconstructions could be done. In addition, he refused for amputation.
      CONCLUSION: Wide excision total calcaneoctomy, bone allograft reconstruction and
      soft tissue coverage with sural flap is a good option for surgical management in
      aggressive GCT of calcaneus instead of amputation.

PMID- 27718437
TI  - Extreme oncoplastic breast surgery: A case report.
AB  - INTRODUCTION: So called "extreme oncoplastic surgery" is emerging as a new
      promising concept in breast cancer surgery allowing successful breast
      conservation in selected patients with multicentric tumors. PRESENTATION OF CASE:
      We report the case of a 48-year-old woman presenting with a multicentric breast
      cancer and successfully treated with an oncoplastic technique consisting in three
      radical lumpectomies followed by breast reshaping and simultaneous contralateral
      symmetrization. DISCUSSION: According to our experience, oncoplastic conserving
      breast surgery could represent a better option than the combination of
      mastectomy, reconstruction and radiation therapy, in terms of quality of life for
      selected patients affected by multicentric breast cancer. CONCLUSION: The
      surgical treatment for multicentric breast cancers remains controversial even
      though emerging evidences show good oncological and aesthetic outcomes following
      oncoplastic conserving breast surgery.

PMID- 27718438
TI  - Urological injuries associated with pelvic fractures: A case report of a detached
      bone segment inside the bladder.
AB  - INTRODUCTION: Urological injuries in pelvic fractures are noticed in 6-15% of the
      cases. The bladder, due to its anatomical position, is prone to rupture in pelvic
      fractures. The majority of urinary bladder injuries are either extraperitoneal or
      intraperitoneal. Nonetheless, both types can occur simultaneously in 6% of the
      cases. PRESENTATION OF THE CASE: A 45-year-old male was brought to our emergency
      department after being struck by an automobile. In the absence of signs of
      urethral injury, a Foley's catheter was inserted revealing gross hematuria. The
      radiological assessment showed bilateral non-displacement sacral wing fractures,
      bilateral non-displacement anterior column fractures and bilateral comminuted
      superior and inferior pubic rami fractures, with a detached pubic bone fragment
      displaced posteriorly. A CT cystogram was performed showing intraperitoneal and
      extraperitoneal extravasation of contrast. The patient was taken to surgery. A
      sharp-edged bony fragment was discovered inside the bladder. A two-layer closure
      of the bladder was performed. DISCUSSION: Pelvic fractures with concomitant lower
      urinary tract injuries are associated with high morbidity and mortality. The
      signs indicative of bladder rupture include a more than one centimeter diastasis
      of the symphysis pubis and a displaced fracture of more than one centimeter
      involving the obturator ring. However, the signs may not be present as in our
      case. CONCLUSION: This unusual case illustrates the potential risk of bladder
      injury following stable pelvic fractures through a detached bone segment. It also
      emphasizes on having a high index of suspicion. The teamwork and
      multidisciplinary approach are essential for an optimal outcome.

PMID- 27718439
TI  - Case report of cadaveric kidney transplantation with renal-portal venous
      drainage: A feasible way for a venous drainage in a complex generalized
      thrombosed vessels setting.
AB  - INTRODUCTION: One of the frequent complications suffered by patients with chronic
      renal failure is the lack of vascular access due to venous thrombosis. This means
      that the transplant surgeon must have a detailed knowledge of the intra-abdominal
      venous system, and other alternative surgeries, at the time of performing the
      renal graft implant, in order to ensure a good venous drainage. PRESENTATION OF
      THE CASE: This article provides a case report regarding a patient with no
      vascular access and with surgical difficulties at the time of the kidney
      transplant, in whom a renal-portal venous drainage was performed with very good
      outcome. DISCUSION: Renal-portal venous drainage is a way to performe kidney
      transplant with good outcome. In Fundacion Valle del Lili we have overcome the
      lack of vascular access in patients that need a renal transplant by new surgical
      technics that improve the patients quality of life and survival. CONCLUSION: We
      can conclude that new surgical alternatives exist for those patients with chronic
      renal failure that have no vascular access. These patients are a priority for
      kidney transplants and the surgeon must take in to account the need for a new
      surgical assessment.

PMID- 27718440
TI  - An interesting case report of vertebral artery dissection following polytrauma.
AB  - INTRODUCTION: The authors present an interesting case of a 19-year-old male who
      presented as a polytrauma patient following a fall from a height. PRESENTATION OF
      CASE: He was initially managed on the intensive care unit with intracranial
      pressure bolt monitoring after being intubated and sedated and having his other
      traumatic injuries stabilized. Upon attempting to wean sedation and extubation a
      repeat CT scan of the head was undertaken and showed a new area suggested of
      cerebral infarction, this was a new finding. Further imaging found that he had a
      cervical vertebral artery dissection following this polytrauma mode of injury.
      DISCUSSION: The incidence of vertebral artery dissection following generalized or
      local trauma is rising but routine imaging/screening in these patients is not
      undertaken. CONCLUSION: Our report displays select images related to this case
      report and emphasizes the consideration of routine imaging in head and neck
      traumatic injuries to diagnose internal carotid and/or vertebral artery
      dissections much earlier.

PMID- 27718441
TI  - Promising in vitro and in vivo inhibition of multidrug-resistant Helicobacter
      pylori by linezolid and novel oxazolidinone analogues.
AB  - The objective of this study was to investigate the prevalence of drug-resistant
      Helicobacter pylori in Beijing Tian Tan Hospital (Beijing, China) and to
      determine the susceptibility of H. pylori to linezolid and novel oxazolidinone
      analogues. Minimum inhibitory concentrations (MICs) of amoxicillin,
      clarithromycin, metronidazole, ciprofloxacin, tetracycline and levofloxacin
      against H. pylori were determined by Etest. The in vitro antibacterial activities
      of linezolid and novel oxazolidinone analogues were assessed by the disk
      diffusion method. In vivo antibacterial activities were determined by
      intragastric administration and stomach CFU counting. Drug resistance patterns
      were serious among clinical H. pylori isolates, with a rate of multidrug
      resistant H. pylori of 10.1%. Linezolid was observed to exhibit in vitro
      activity, with MICs ranging from <=0.25mg/L to 32mg/L against clinical H. pylori
      isolates (MIC50, 2mg/L; MIC90, 8mg/L). The oxazolidinone analogue sy142
      demonstrated better antimicrobial activity than linezolid in vitro. These results
      indicate that oxazolidinones may be appropriate agents to treat drug-resistant H.
      pylori. Further clinical trials should be performed to confirm this.

PMID- 27718442
TI  - Utility of Impella(r) left ventricular assist device during cardiac arrest: A
      case report.

PMID- 27718443
TI  - Use of serum levels of high sensitivity troponin T, galectin-3 and C-terminal
      propeptide of type I procollagen at long term follow-up in heart failure patients
      with reduced ejection fraction: Comparison with soluble AXL and BNP.
AB  - BACKGROUND: Prognostic biomarkers are needed to improve the management of the
      heart failure (HF) epidemic, being the brain natriuretic peptides the most
      valuable. Here we evaluate 3 biomarkers, high sensitivity troponin T (hs-TnT),
      galectin-3 (Gal-3) and C-terminal propeptide of type I procollagen (CICP),
      compare them with a recently described new candidate (sAXL), and analyze their
      relationship with BNP. METHODS: HF patients with reduced ejection fraction
      (n=192) were included in this prospective observational study, with measurements
      of candidate biomarkers, functional, clinical and echocardiographic variables. A
      Cox regression model was used to determine predictors for clinical events, i.e.
      all-cause mortality and heart transplantation. RESULTS: Hs-TnT circulating values
      were correlated to clinical characteristics indicative of more advanced HF. When
      analyzing the event-free survival at a mean follow-up of 3.6years, patients in
      the higher quartile of either BNP, hs-TnT, CICP and sAXL had increased risk of
      suffering a clinical event, but not Gal-3. Combination of high sAXL and BNP
      values had greater predictive value (HR 6.8) than high BNP alone (HR 4.9). In a
      multivariate Cox regression analysis, BNP, sAXL and NYHA class were independent
      risk factors for clinical events. CONCLUSIONS: In this HF cohort, hs-TnT is a
      good HF marker and has a very significant prognostic value. The prognostic value
      of CICP and sAXL was of less significance. However, hs-TnT did not add predictive
      value to BNP, while sAXL did. This suggests that elevated troponin has a common
      origin with BNP, while sAXL could represent an independent pathological
      mechanism.

PMID- 27718444
TI  - Conversion of persistent atrial fibrillation to sinus rhythm after LAA ligation
      with the LARIAT device.

PMID- 27718445
TI  - Cardiovascular effects of SPARK conducted electrical weapon in healthy subjects.
AB  - BACKGROUND: The increasing use of conducted electronic weapons (CEW) cause
      concern regarding its secure application, specially regarding the implications in
      the cardiovascular system. METHODS: The objective was to determine Spark CEW
      safety through cardiovascular parameters analysis of healthy volunteers subjected
      to its use. RESULTS: Volunteers over 18years without cardiovascular disease or
      recent use of illegal drugs were submitted, before and after being affected with
      Spark CEW, to clinical evaluation; blood collection for serum laboratory tests;
      transthoracic electrocardiography at rest, transthoracic echodopplercardiogram
      and 24hour Holter. RESULTS: All 71 patients reported being incapable of any
      voluntary reaction during the shock of the application time. No arrhythmia or
      myocardial necrosis was related to the use of non-lethal weapon SPARK. Reported
      adverse events were self-limited, and mostly mild. CONCLUSIONS: SPARK brand CEW
      is effective in incapacitating individuals by the shock of the application time,
      without causing.

PMID- 27718446
TI  - Catheter-directed treatment for acute pulmonary embolism: Systematic review and
      single-arm meta-analyses.
AB  - BACKGROUND: We sought to estimate the efficacy and safety outcomes of catheter
      directed treatment (CDT) for patients with acute pulmonary embolism (PE).
      METHODS: We searched SCOPUS for studies reporting outcomes after CDT for acute
      PE. Studies were categorized in three groups for analyses due to heterogeneity in
      the classification of acute PE: 1) patients with PE causing right ventricular
      dysfunction and haemodynamic instability: unstable haemodynamic status, 2)
      patients with PE causing right ventricular dysfunction where study outcomes were
      not stratified by haemodynamic status: stable and unstable haemodynamic status,
      and 3) patients with PE causing right ventricular dysfunction who remained
      haemodynamically stable: stable haemodynamic status. Efficacy and safety outcomes
      were estimated and presented as point estimates with 95% confidence intervals.
      RESULTS: In 35 studies with 1253 patients, 1277 CDTs were performed. The in
      hospital mortality rates for the unstable haemodynamic status, stable and
      unstable haemodynamic status, and stable haemodynamic status groups were 18.1%
      (7.3-38.2%), 7.1% (5.0-10.1%), and 2.6% (0.8-7.3%), respectively. The major
      bleeding rates across the groups were estimated to be 4.5, 8.5 and 3.9 per 100
      CDTs, respectively. Minor bleeding occurred in 6.2, 11.9 and 9.1 per 100 CDTs,
      respectively. After CDT, all groups had improvements in mean pulmonary artery
      pressure and right ventricular function. CONCLUSIONS: We provide descriptive
      measures of efficacy and safety for patients who underwent CDT for acute PE.

PMID- 27718447
TI  - Targeting B cells in treatment of autoimmunity.
AB  - B cells have emerged as effective targets for therapeutic intervention in
      autoimmunities in which the ultimate effectors are antibodies, as well as those
      in which T cells are primary drivers of inflammation. Proof of this principle has
      come primarily from studies of the efficacy of Rituximab, an anti-CD20 mAb that
      depletes B cells, in various autoimmune settings. These successes have inspired
      efforts to develop more effective anti-CD20s tailored for specific needs, as well
      as biologicals and small molecules that suppress B cell function without the
      risks inherent in B cell depletion. Here we review the current status of B cell
      targeted therapies for autoimmunity.

PMID- 27718448
TI  - Endoplasmic reticulum stress in beta cells and autoimmune diabetes.
AB  - Type 1 diabetes results from the autoimmune destruction of pancreatic beta cells,
      leading to insulin deficiency and hyperglycemia. Although multiple attempts have
      been made to slow the autoimmune process using immunosuppressive or
      immunomodulatory agents, there are still no effective treatments that can delay
      or reverse the progression of type 1 diabetes in humans. Recent studies support
      endoplasmic reticulum (ER) as a novel target for preventing the initiation of the
      autoimmune reaction, propagation of inflammation, and beta cell death in type 1
      diabetes. This review highlights recent findings on ER stress in beta cells and
      development of type 1 diabetes and introduces potential new treatments targeting
      the ER to combat this disorder.

PMID- 27718449
TI  - AMECM/DCB scaffold prompts successful total meniscus reconstruction in a rabbit
      total meniscectomy model.
AB  - Tissue-engineered meniscus regeneration is a very promising treatment strategy
      for meniscus lesions. However, generating the scaffold presents a huge challenge
      for meniscus engineering as this has to meet particular biomechanical and
      biocompatibility requirements. In this study, we utilized acellular meniscus
      extracellular matrix (AMECM) and demineralized cancellous bone (DCB) to construct
      three different types of three-dimensional porous meniscus scaffold: AMECM, DCB,
      and AMECM/DCB, respectively. We tested the scaffolds' physicochemical
      characteristics and observed their interactions with meniscus fibrochondrocytes
      to evaluate their cytocompatibility. We implanted the three different types of
      scaffold into the medial knee menisci of New Zealand rabbits that had undergone
      total meniscectomy; negative control rabbits received no implants. The
      reconstructed menisci and corresponding femoral condyle and tibial plateau
      cartilage were all evaluated at 3 and 6 months (n = 8). The in vitro study
      demonstrated that the AMECM/DCB scaffold had the most suitable biomechanical
      properties, as this produced the greatest compressive and tensile strength
      scores. The AMECM/DCB and AMECM scaffolds facilitated fibrochondrocyte
      proliferation and the secretion of collagen and glycosaminoglycans (GAGs) more
      effectively than did the DCB scaffold. The in vivo experiments demonstrated that
      both the AMECM/DCB and DCB groups had generated neomeniscus at both 3 and 6
      months post-implantation, but there was no obvious meniscus regeneration in the
      AMECM or control groups, so the neomeniscus analysis could not perform on AMECM
      and control group. At both 3 and 6 months, histological scores were better for
      regenerated menisci in the AMECM/DCB than in the DCB group, and significantly
      better for articular cartilage in the AMECM/DCB group compared with the other
      three groups. Knee MRI scores (Whole-Organ Magnetic Resonance Imaging Scores
      (WORMS)) were better in the AMECM/DCB group than in the other three groups at
      both 3 and 6 months. At both 3 and 6 months, RT-PCR demonstrated that aggrecan,
      Sox9, and collagen II content was significantly higher, and mechanical testing
      demonstrated greater tensile strength, in the AMECM/DCB group neomenisci compared
      with the DCB group.

PMID- 27718450
TI  - Interaction of imatinib mesylate with human serum transferrin: The comparative
      spectroscopic studies.
AB  - Imatinib mesylate (Imt) is a tyrosine kinase inhibitor mainly used in the
      treatment of Philadelphia chromosome-positive chronic myelogenous leukemia
      (Ph+CML). Human serum transferrin is the most abundant serum protein responsible
      for the transport of iron ions and many endogenous and exogenous ligands. In this
      study the mechanism of interactions between the imatinib mesylate and all states
      of transferrin (apo-Tf, Htf and holo-Tf) has been investigated by fluorescence,
      ultraviolet-visible (UV-vis), circular dichroism (CD) and zeta potential
      spectroscopic methods. Based on the experimental results it was proved that under
      physiological conditions the imatinib mesylate binds to the each form of
      transferrin with a binding constant c.a. 105M-1. The thermodynamic parameters
      indicate that hydrogen bonds and van der Waals were involved in the interaction
      of apo-Tf with the drug and hydrophobic and ionic strength participate in the
      reaction of Htf and holo-Tf with imatinib mesylate. Moreover, it was shown that
      common metal ions, Zn2+ and Ca2+ strongly influenced apo-Tf-Imt binding constant.
      The CD studies showed that there are no conformational changes in the secondary
      structure of the proteins. No significant changes in secondary structure of the
      proteins upon binding with the drug and instability of apo-Tf-Imt system are the
      desirable effects from pharmacological point of view.

PMID- 27718451
TI  - Hyperspectral Raman imaging of human prostatic cells: An attempt to differentiate
      normal and malignant cell lines by univariate and multivariate data analysis.
AB  - Hyperspectral Raman images of human prostatic cells have been collected and
      analysed with several approaches to reveal differences among normal and tumor
      cell lines. The objective of the study was to test the potential of different
      chemometric methods in providing diagnostic responses. We focused our analysis on
      the nu(CH) region (2800-3100cm-1) owing to its optimal Signal-to-Noise ratio and
      because the main differences between the spectra of the two cell lines were
      observed in this frequency range. Multivariate analysis identified two principal
      components, which were positively recognized as due to the protein and the lipid
      fractions, respectively. The tumor cells exhibited a modified distribution of the
      cytoplasmatic lipid fraction (mainly localized alongside the cell boundary) which
      may result very useful for a preliminary screening. Principal Component analysis
      was found to provide high contrast and to be well suited for image-processing
      purposes. Self-Modelling Curve Resolution made available meaningful spectra and
      relative-concentration values; it revealed a 97% increase of the lipid fraction
      in the tumor cell with respect to the control. Finally, a univariate approach
      confirmed significant and reproducible differences between normal and tumor
      cells.

PMID- 27718452
TI  - A post-decoding re-ranking algorithm for predicting interacting residues in
      proteins with hidden Markov models incorporating long-distance information.
AB  - Protein-protein interactions play a central role in the biological processes of
      cells. Accurate prediction of the interacting residues in protein-protein
      interactions enhances understanding of the interaction mechanisms and enables in
      silico mutagenesis, which can help facilitate drug design and deepen our
      understanding of the inner workings of cells. Correlations have been found among
      interacting residues as a result of selection pressure to retain the interaction
      during evolution. In previous work, incorporation of such correlations in the
      interaction profile hidden Markov models with a special decoding algorithm (ETB
      Viterbi) has led to improvement in prediction accuracy. In this work, we first
      demonstrated the sub-optimality of the ETB-Viterbi algorithm, and then
      reformulated the optimality of decoding paths to include correlations between
      interacting residues. To identify optimal decoding paths, we propose a post
      decoding re-ranking algorithm based on a genetic algorithm with simulated
      annealing and show that the new method gains an increase of near 14% in
      prediction accuracy over the ETB-Viterbi algorithm.

PMID- 27718453
TI  - Parental reflective functioning among mothers with eating disorder
      symptomatology.
AB  - OBJECTIVE: Reflective Functioning is a vital aspect of parental aptitude and its
      absence, especially in the presence of psychopathology, can impair attachment.
      This study sought to clarify the relationship of parental RF among mothers with
      eating disorder symptomatology. METHOD: We assessed 59 mothers for ED
      symptomatology using the Eating Disorder Examination Questionnaire (EDE-Q) and RF
      through the Parental Reflective Functioning Questionnaire (PRFQ). Bivariate and
      multivariate analyses compared PRFQ subscales between symptomatic and
      asymptomatic mothers, using a clinical cutoff score of 4 on the EDE-Q subscales.
      RESULTS: Greater weight and shape concerns were found to significantly predict
      higher RF (p=0.023; p=0.026). DISCUSSION: This finding could indicate a similar
      pattern seen among individuals with bulimia nervosa; individuals have higher RF
      scores, although affect regulation may still be limited. More research is needed
      with a larger sample to define the relationship between ED symptomatology and RF
      and identify potential mediators and moderators.

PMID- 27718454
TI  - Association of binge eating behavior and psychiatric comorbidity in ELSA-Brasil
      study: Results from baseline data.
AB  - OBJECTIVE: To estimate the association of binge eating behavior (BE) with common
      mental disorders (CMD). METHOD: Cross sectional investigation of 14,088 adults,
      aged 35-74years (ELSA-Brasil study). BE was assessed with Structured Clinical
      Interview for DSM Disorders (SCID - DSM IV) questions, and psychiatric morbidity
      with CIS-R (CIS R - Clinical Interview Schedule Revised). Poisson regression was
      used to estimate the association of BE and psychiatric morbidity. RESULTS:
      Adjusted prevalence ratios (PR) for CMD and BE were: PR=1.60 (1.34-1.91) for a
      CIS R score 12-18 (presence of CMD with lower clinical severity); PR=2.40 (2.06
      2.80) for a CIS R score>=18 (severe symptom profile likely to require treatment);
      for psychiatric diagnoses: PR=2.24 (1.84-2.73) for depressive episodes; PR=1.77
      (1.53-2.04) for anxiety disorders, and PR=1.42 (1.20-1.67) for mixed depressive
      anxiety disorder. CONCLUSION: BE was associated with higher prevalence of common
      mental disorders. Our findings highlight the need to investigate mechanisms
      involved in the relationship of BE, obesity and psychopathology in low/middle
      income countries.

PMID- 27718455
TI  - Molecular mechanisms in compatibility and mechanical properties of
      Polyacrylamide/Polyvinyl alcohol blends.
AB  - The objectives of this study were to develop a computational model based on
      molecular dynamics technique to investigate the compatibility and mechanical
      properties of Polyacrylamide (PAM)/Polyvinyl alcohol (PVA) blends. Five
      simulation models of PAM/PVA with different composition ratios (4/0, 3/1, 2/2,
      1/3, 0/4) were constructed and simulated by using molecular dynamics (MD)
      simulation. The interaction mechanisms of molecular chains in PAM/PVA blend
      system were elaborated from the aspects of the compatibility, mechanical
      properties, binding energy and pair correlation function, respectively. The
      computed values of solubility parameters for PAM and PVA indicate PAM has a good
      miscibility with PVA. The results of the static mechanical analysis, based on the
      equilibrium structures of blends with differing component ratios, shows us that
      the elastic coefficient, engineering modulus, and ductility are increased with
      the addition of PVA content, which is 4/0 PAM/PVA<3/1 PAM/PVA<2/2 PAM/PVA<1/3
      PAM/PVA<0/4 PAM/PVA. Moreover, binding energy results indicate that a stronger
      interaction exists among PVA molecular chains comparing with PAM molecular
      chains, which is why the mechanical properties of blend system increasing with
      the addition of PVA content. Finally, the results of pair correlation functions
      (PCFs) between polar functional groups and its surrounding hydrogen atoms,
      indicated they interact with each other mainly by hydrogen bonds, and the
      strength of three types of polar functional groups has the order of O(-OH)>O(
      C=O)>N(-NH2). This further elaborates the root reason why the mechanical
      properties of blend system increase with the addition of PVA content.

PMID- 27718456
TI  - Validation of the Seven Up Seven Down Inventory in bipolar offspring: screening
      and prediction of mood disorders. Findings from the Dutch Bipolar Offspring
      Study.
AB  - OBJECTIVE: To validate the Seven Up Seven Down (7U7D), an abbreviated version of
      the General Behavior Inventory (GBI), as screener for mood disorders and test its
      ability to predict mood disorders over time in individuals at risk for bipolar
      disorder (BD). METHODS: Bipolar offspring (n=108) were followed from adolescence
      into adulthood and assessed at baseline, 1-, 5- and 12 years follow-up (T1-T4
      respectively). Offspring were assessed using the Schedule for Affective Disorders
      and Schizophrenia for School-Age Children--Present and Lifetime Version,
      Structured Clinical Interview for DSM-IV Axis I Disorders and the GBI. RESULTS:
      Performance of the GBI and 7U7D was functionally similar for the depression (7D)
      scale, but variable for the mania (7U) scale. As screener for mood disorders
      (T4), the 7D showed fair diagnostic efficiency (area under the curve (AUC) 0.68,
      p<0.01, OR 1.53, 95% CI 1.15-2.03). The discriminative validity for BD and
      unipolar disorder was only close to significant (7D AUC 0.66, p=0.078; 7U AUC
      0.67, p=0.067). In terms of prediction of mood disorder onset between T1 and T4,
      the 7D, but not the 7U, was associated with new onset (AUC 0.67, p<0.05; HR 1.14,
      95% CI 1.07-1.23). The 7U7D did not achieve significant prediction of BD.
      LIMITATIONS: Relative small sample size and limited generalizability.
      CONCLUSIONS: Based on the current study, the 7U7D shows limited potential as
      screening instrument for mood disorders in bipolar offspring. The clinical
      utility of the 7U7D needs further exploration for use in clinical and research
      settings.

PMID- 27718457
TI  - Nuclear export signal of PRRSV NSP1alpha is necessary for type I IFN inhibition.
AB  - The nonstructural protein 1alpha (NSP1alpha) of porcine reproductive and
      respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that
      suppresses the production of type I interferon (IFN). In this study, we
      investigated the relationship between the subcellular distribution of NSP1alpha
      and its inhibition of type I IFN. NSP1alpha was found to contain the classical
      nuclear export signal (NES) and NSP1alpha nuclear export was CRM-1-mediated.
      NSP1alpha was shuttling between the nucleus and cytoplasm. We also showed that
      the nuclear export of NSP1alpha was necessary for its ability for type I IFN
      inhibition. NSP1alpha was also found to interact with CBP, which implies a
      possible mechanism of CBP degradation by NSP1alpha. Taken together, our results
      describe a novel mechanism of PRRSV NSP1alpha for type I IFN inhibition and
      suppression of the host innate antiviral response.

PMID- 27718459
TI  - DIADECOMP: A new approach to analyze decompositions from projection spectroscopy.
AB  - We demonstrate for the first time a complete small protein characterization with
      the projection-decomposition approach, including full assignments as well as
      determination of the 3D fold. In TOCSY- and NOESY-type 4D experiments, pairing of
      signals from hydrogens and from their respective heavy atoms in decompositions
      represents a new problem. An approach, referred to as "DIADECOMP" (diagonal
      decomposition), is introduced to solve this problem; it consists of two separate
      decompositions of the input projections, differing in a 45 degrees  rotation of
      the spectral axes. While DIADECOMP requires a somewhat complex formulation, in
      practice it results in observing signals in the rotated decompositions that
      correspond to sums or differences of frequencies. When applied to a small
      protein, human defensin beta6, the analysis of a HCC(CO)NH-TOCSY with DIADECOMP
      results in largely unambiguous assignments of the aliphatic side chain groups.
      Furthermore, DIADECOMP applied to a 15N-HSQC-NOESY-15N-HSQC provides all expected
      short distances between amide groups (defined as all HN-HN distances <3.5A in a
      reference structure). It is worth noting that short HN-HN distances unambiguously
      define alpha-helices, the alignment of beta-strands in sheets, as well as the
      presence of beta-bulges. This approach of using a minimal amount of NMR data,
      namely four projection experiments recorded in ~2.5days, resulted for the human
      defensin beta6 in complete assignments and a backbone fold with a RMSD of the non
      flexible structure of 0.6A. Uniqueness of decompositions specifically from TOCSY-
      and NOESY-type 4D experiments is discussed.

PMID- 27718458
TI  - Health-related quality of life assessment in contemporary phase III trials in
      advanced colorectal cancer.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is often used as an endpoint
      in cancer clinical trials. We assessed the frequency and correlates of HRQOL use
      in phase III trials in advanced colorectal cancer. METHODS: We searched PubMed
      for phase III trials published between January 1998 and December 2014, as well as
      for companion papers reporting on HRQOL separately. We excluded papers reporting
      on correlative biology or prognostic factors in isolation from the main trial
      results, as well as trials on supportive care and on local therapy. RESULTS: We
      retrieved 111 trials that enrolled a total of 61,531 patients in 241 trial arms.
      HRQOL was reportedly used as an endpoint in 40 trials (36%), in all but two as a
      secondary endpoint. There was a significant decrease in the use of HRQOL, with
      frequencies of 46% in trials published between 1998 and 2006, and 27% between
      2007 and 2014 (P=0.04). Trials with HRQOL as endpoint were significantly larger
      than trials without such endpoint. Formal statistical comparisons involving HRQOL
      parameters were reported in 36 of 40 trials (90%) with HRQOL assessment, with a
      significant difference between arms found in 14 (39%), six of which favoring the
      experimental arm. HRQOL gains were usually accompanied by improvements in
      efficacy endpoints, but were not related to the number of patients or
      chemotherapy line. CONCLUSIONS: HRQOL has been formally assessed in about one
      third of recent phase III trials in advanced colorectal cancer, with a
      significant gain in HRQOL in about 40% of cases. It is questionable whether HRQOL
      results may largely help select between competing treatments. This assumption may
      be one of the reasons for the apparent decreased use of HRQOL as an endpoint in
      phase III trials in this disease.

PMID- 27718460
TI  - Sculpting 3D spatial selectivity with pairs of 2D pulses: A comparison of
      methods.
AB  - Enhancing the specificity of the spins' excitation can improve the capabilities
      of magnetic resonance. Exciting voxels with tailored 3D shapes reduces partial
      volume effects and enhances contrast, particularly in cases where cubic voxels or
      other simple geometries do not provide an optimal localization. Spatial
      excitation profiles of arbitrary shapes can be implemented using so-called
      multidimensional RF pulses, which are often limited in practice to 2D
      implementations owing to their sensitivity to field inhomogeneities. Recent work
      has shown the potential of spatio-temporally encoded (SPEN) pulses towards
      alleviating these constraints. In particular, 2D pulses operating in a so-called
      hybrid scheme where the "low-bandwidth" spatial dimension is sculpted by a SPEN
      strategy while an orthogonal axis is shaped by regular k-space encoding, have
      been shown resilient to chemical shift and B0 field inhomogeneities. In this work
      we explore the use of pairs of 2D pulses, with one of these addressing geometries
      in the x-y plane and the other in the x-z dimension, to sculpt complex 3D volumes
      in phantoms and in vivo. To overcome limitations caused by the RF discretization
      demanded by these 2D pulses, a number of "unfolding" techniques yielding images
      from the centerband RF excitation while deleting sideband contributions - even in
      cases where center- and side-bands severely overlap - were developed. Thus it was
      possible to increase the gradient strengths applied along the low bandwidth
      dimensions, significantly improving the robustness of this kind of 3D sculpting
      pulses. Comparisons against conventional pulses designed on the basis of pure k
      space trajectories, are presented.

PMID- 27718461
TI  - Iptakalim induces mitochondria-dependent apoptosis in hypoxic rat pulmonary
      arterial smooth muscle cells.
AB  - OBJECTIVES: Pulmonary vascular medial hypertrophy in hypoxic pulmonary arterial
      hypertension (HPH) is caused in part by decreased apoptosis in pulmonary artery
      smooth muscle cells (PASMCs). Iptakalim (Ipt), an ATP sensitive potassium channel
      opener, ameliorates HPH in animal models. Here we investigated the effects of Ipt
      on proliferation and apoptosis of hypoxic rat PASMCs, and to determine the
      possible underlying mechanisms. METHODS: Primary rat PASMCs were isolated and
      cultured. PASMCs were cultured for 24h in normoxia or hypoxia (5% O2) conditions
      with and without Ipt. Cell proliferation and cycle were determined by MTT assay
      and flow cytometry, respectively. Mitochondrial membrane potential (Deltaym) was
      detected by fluorescence microscope Western blot assays were used to examine the
      expression of cyclin D, CDK4, endothelin-1 (ET-1), hypoxia-inducible factor-1
      (HIF-1), platelet-derived growth factor-BB (PDGF-BB), Bax, Bcl-2, cytochrome c
      (Cyt c), caspase-9, and caspase-3 in PASMCs. RESULTS: We found that hypoxia
      significantly stimulated proliferation and rendered resistance to apoptosis in
      PASMCs. Ipt suppressed proliferation and induced cell cycle arrest in hypoxia
      PASMCs. Ipt decreased the expression of cyclin D, CDK4, HIF-1, ET-1, and PDGF-BB
      in hypoxia PASMCs. It reversed the depolarization of Deltapsim in hypoxia PASMCs
      too. Ipt significantly upregulated Bax expression and downregulated Bcl-2
      expression, and promoted the release of Cyt c from mitochondria to cytoplasm in
      hypoxia PASMCs. Furthermore, Ipt significantly activated the caspase cascades
      evidenced by increased expression of caspase-9 and caspase-3 in hypoxia PASMCs.
      CONCLUSIONS: Ipt could inhibit cell proliferation and induce apoptosis associated
      with cell cycle arrest, decreased ET-1, HIF-1, cyclin D, CDK4, PDGF-BB and
      Deltapsim, increased Bax/Bcl-2 ratio, enhanced Cyt c release, and activation of
      caspases in PASMCs under hypoxia status. Our data indicated that Ipt could be a
      therapeutic candidate for treatment of HPH.

PMID- 27718462
TI  - Towards patient-specific modeling of mitral valve repair: 3D transesophageal
      echocardiography-derived parameter estimation.
AB  - Transesophageal echocardiography (TEE) is routinely used to provide important
      qualitative and quantitative information regarding mitral regurgitation.
      Contemporary planning of surgical mitral valve repair, however, still relies
      heavily upon subjective predictions based on experience and intuition. While
      patient-specific mitral valve modeling holds promise, its effectiveness is
      limited by assumptions that must be made about constitutive material properties.
      In this paper, we propose and develop a semi-automated framework that combines
      machine learning image analysis with geometrical and biomechanical models to
      build a patient-specific mitral valve representation that incorporates image
      derived material properties. We use our computational framework, along with 3D
      TEE images of the open and closed mitral valve, to estimate values for chordae
      rest lengths and leaflet material properties. These parameters are initialized
      using generic values and optimized to match the visualized deformation of mitral
      valve geometry between the open and closed states. Optimization is achieved by
      minimizing the summed Euclidean distances between the estimated and image-derived
      closed mitral valve geometry. The spatially varying material parameters of the
      mitral leaflets are estimated using an extended Kalman filter to take advantage
      of the temporal information available from TEE. This semi-automated and patient
      specific modeling framework was tested on 15 TEE image acquisitions from 14
      patients. Simulated mitral valve closures yielded average errors (measured by
      point-to-point Euclidean distances) of 1.86 +/- 1.24 mm. The estimated material
      parameters suggest that the anterior leaflet is stiffer than the posterior
      leaflet and that these properties vary between individuals, consistent with
      experimental observations described in the literature.

PMID- 27718463
TI  - Simultaneous quantification of soman and VX adducts to butyrylcholinesterase,
      their aged methylphosphonic acid adduct and butyrylcholinesterase in plasma using
      an off-column procainamide-gel separation method combined with UHPLC-MS/MS.
AB  - This work describes a novel and sensitive non-isotope dilution method for
      simultaneous quantification of organophosphorus nerve agents (OPNAs) soman (GD)
      and VX adducts to butyrylcholinesterase (BChE), their aged methylphosphonic acid
      (MeP) adduct and unadducted BChE in plasma exposed to OPNA. OPNA-BChE adducts
      were isolated with an off-column procainamide-gel separation (PGS) from plasma,
      and then digested with pepsin into specific adducted FGES*AGAAS nonapeptide (NP)
      biomarkers. The resulting NPs were detected by UHPLC-MS/MS MRM. The off-column
      PGS method can capture over 90% of BChE, MeP-BChE, VX-BChE and GD-BChE from their
      respective plasma materials. One newly designed and easily synthesized
      phosphorylated BChE nonapeptide with one Gly-to-Ala mutation was successfully
      reported to serve as internal standard instead of traditional isotopically
      labeled BChE nonapeptide. The linear range of calibration curves were from 1.00
      200ngmL-1 for VX-NP, 2.00-200ngmL-1 for GD-NP and MeP-NP (R2>=0.995), and 3.00
      200ngmL-1 for BChE NP (R2>=0.990). The inter-day precision had relative standard
      deviation (%RSD) of <8.89%, and the accuracy ranged between 88.9-120%. The limit
      of detection was calculated to be 0.411, 0.750, 0.800 and 1.43ngmL-1 for VX-NP,
      GD-NP, MeP-NP and BChE NP, respectively. OPNA-exposed quality control plasma
      samples were characterized as part of method validation. Investigation of plasma
      samples unexposed to OPNA revealed no baseline values or interferences. Using the
      off-column PGS method combined with UHPLC-MS/MS, VX-NP and GD-NP adducts can be
      unambiguously detected with high confidence in 0.10ngmL-1 and 0.50ngmL-1 of
      exposed human plasma respectively, only requiring 0.1mL of plasma sample and
      taking about four hours without special sample preparation equipment. These
      improvements make it a simple, sensitive and robust PGS-UHPLC-MS/MS method, and
      this method will become an attractive alternative to immunomagnetic separation
      (IMS) method and a useful diagnostic tool for retrospective detection of OPNA
      exposure with high confidence. Furthermore, using the developed method, the
      adducted BChE levels from VX and GD-exposed (0.10-100ngmL-1) plasma samples were
      completely characterized, and the fact that VX being more active and specific to
      BChE than GD was re-confirmed.

PMID- 27718464
TI  - Validation of a novel and rapid method for the simultaneous determination of some
      phenolic organohalogens in human serum by GC-MS.
AB  - Over the last decades, more and more studies focused on the impact of endocrine
      disruptors on the environment and human health. Among them, phenolic
      organohalogens (POHs) are a particular concern because of their structural
      resemblance with natural hormones. There are different methods that are known to
      quantify these compounds in human serum, however, the current extraction
      techniques are long, fastidious and using harmfull chemicals such as diazomethane
      and sulfuric acid. Consequently, we developed an alternative, sensitive and
      faster method to simultaneously quantify pentachlorophenol (PCP),
      tetrabromobisphenol A (TBBPA), 4 bromophenols, 7 hydroxypolychlorinated biphenyls
      (OH-PCBs) and 3 hydroxy-polybrominated diphenyl ether (OH-PBDEs) in human serum
      sample. The clean-up and the enrichment of the sample were performed in a single
      extraction step using strong anion-exchange solid phase cartridge. After a rapid
      liquid-liquid extraction step to remove acidic traces, the extract was
      derivatized using trimethylsilyldiazomethane (TMSD) and finally analyzed by a gas
      chromatograph coupled with an electron negative capture chemical ionization
      source combined with a triple quadrupole mass spectrometer (GC-ENCI-MS) operating
      in single ion monitoring. The whole procedure was validated according to the
      total error approach. The inter and intra assay precision were demonstrated to be
      lower than 20% and the relative bias to be lower than 15% in the dosing range of
      concentrations. The limit of quantification (LOQ) ranged from 2pgmL-1 and 5pgmL
      1, except for the PCP (44.6pgmL-1) and for the 2,4,6-tribromophenol (49.6pgmL-1).
      Finally, the method was successfully applied to measure the POH background
      contamination in serum samples collected from 20 Belgian blood donors recruited
      in CHU Mont-Godinne (Namur, Belgium) aged between 21 and 69 years old.

PMID- 27718466
TI  - Mental disorders in HIV/HCV coinfected patients under antiviral treatment for
      hepatitis C.
AB  - This paper aims to review the epidemiology and management of mental disorders in
      human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients,
      the need for antiviral therapy in this specific population, and current treatment
      strategies for HIV/HCV patients with psychiatric and/or substance use disorders.
      This is a narrative review. Data was sourced from electronic databases and was
      not limited by language or date of publication. HIV infection has become a
      survivable chronic illness. Prevalence of HCV infection among HIV-infected
      patients is high ranging from 50% to 90%. Patients with psychiatric diseases have
      also an increased risk for HIV/HCV coinfection. The most effective strategy to
      decrease HCV-related morbidity and mortality in coinfection is to achieve viral
      eradication. Although psychiatric symptoms often appear during antiviral
      treatment and may be associated with the use of interferon-alpha (IFN-alpha),
      recent evidence suggests that many patients with comorbid mental and substance
      use disorders can be treated safely. Recent data indicate that IFNalpha-induced
      psychiatric side effects have a similar prevalence in HIV/HCV coinfected patients
      than in monoinfected patients and they can be managed and even prevented
      successfully with psychopharmacological strategies in the frame of a
      multidisciplinary team. New antivirals offer INF-free therapies for this specific
      population.

PMID- 27718465
TI  - Analysis of beta-agonist residues in bovine hair: Development of a UPLC-MS/MS
      method and stability study.
AB  - Beta-sympathomimetic compounds are widely used in therapy because of the
      bronchodilator, smooth muscle-relaxant and tocolytic properties. However, their
      growth promoting and performance enhancing effects are often subject to illegal
      use. The present work describes the development of a fast and reliable analytical
      multiresidue method for the confirmation 20 beta-agonist compounds in animal
      hair. The procedure is based on alkaline digestion, LLE with organic solvents,
      SPE clean up and liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)
      analysis, and is suitable for the public Official control of beta-agonist
      residues in hair sample. Validation was performed according to Commission
      Decision 2002/657/EC requirements. Independent samples spiked with the
      investigated compounds in the range 0.2-10.0MUgkg-1 are showing intra-day and
      inter-day precision (RSD) lower than 17.8% and 19.7%, respectively. Linearity,
      measured in the range of 0.1-10.0MUgkg-1, resulted with a Pearson's r>0.996. The
      decision limits (CCalpha) for the all investigated beta agonists resulted in the
      range 0.2-1.0MUgkg-1. Furthermore, the method was tested on real hair samples
      obtained from cattle, known as positive to clenbuterol, in order to check its
      effectiveness and the beta-agonists stability.

PMID- 27718467
TI  - Typology of schizotypy in non-clinical young adults: Psychopathological and
      personality disorder traits correlates.
AB  - Few typological studies address schizotypy in young adults. Schizotypal traits
      were assessed on 466 college students using the Schizotypal Personality
      Questionnaire-Brief (SPQ-B). Other measures evaluated personality traits
      previously associated with schizotypy (borderline, obsessionnal, and autistic
      traits), psychopathological symptoms (suicidal ideations, depressive and
      obsessive-compulsive symptoms) and psychosocial functioning. A factor analysis
      was first performed on SPQ-B results, leading to four factors: negative
      schizotypy, positive schizotypy, social anxiety, and reference ideas. Based on
      these factors, a cluster analysis was conducted, which yielded four clearly
      distinct groups characterized by "Low" (non schizotypy), "High schizotypy" (mixed
      positive and negative), "Positive schizotypy", and "Social impairment". Regarding
      personality disorder traits and psychopathological symptoms, the "High
      schizotypy" cluster scored higher than the "Positive" and the "Social impairment"
      groups, which scored higher than the "Low" cluster. The "Positive" group had
      higher levels of interpersonal relationships than in the "High" and the "Social
      impairment" clusters, suggesting that positive schizotypy was associated to
      benefits such as perceived social relationships. Nevertheless the "Positive"
      cluster was also linked to high levels of personality disorder traits and
      psychopathological symptoms, and to low academic achievement, at levels similar
      those observed in the "Social impairment" cluster, confirming an unhealthy side
      to positive schizotypy.

PMID- 27718468
TI  - Neurocognition in help-seeking individuals at risk for psychosis: Prediction of
      outcome after 24 months.
AB  - An important aim in schizophrenia research is to optimize the prediction of
      psychosis and to improve strategies for early intervention. The objectives of
      this study were to explore neurocognitive performance in individuals at risk for
      psychosis and to optimize predictions through a combination of neurocognitive and
      psychopathological variables. Information on clinical outcomes after 24 months
      was available from 118 subjects who had completed an extensive assessment at
      baseline. Subjects who had converted to psychosis were compared with subjects who
      had not. Multivariate Cox regression analyses were used to determine which
      baseline measure best predicted a conversion to psychosis. The premorbid IQ and
      the neurocognitive domains of processing speed, learning/memory, working memory
      and verbal fluency significantly discriminated between converters and non
      converters. When entered into multivariate regression analyses, the combination
      of PANSS positive/negative symptom severity and IQ best predicted the clinical
      outcomes. Our results confirm previous evidence suggesting moderate premorbid
      cognitive deficits in individuals developing full-blown psychosis. Overall,
      clinical symptoms appeared to be a more sensitive predictor than cognitive
      performance. Nevertheless, the two might serve as complementary predictors when
      assessing the risk for psychosis.

PMID- 27718469
TI  - Depression and anxiety mediate the relationship between temperament and character
      and psychotic-like experiences in healthy subjects.
AB  - In this study we examined the hypothesis that depression and anxiety may mediate
      the relationship between personality traits and both positive and negative
      psychotic-like experiences (PLEs) in healthy adults. The Community Assessment of
      Psychic Experiences (CAPE) scale, Temperament and Character Inventory (TCI), Beck
      Depression Inventory (BDI) and State and Trait Anxiety Inventory (STAI) were
      administered to 492 healthy individuals. Multiple stepwise regression and
      mediation analyses were performed to examine whether depressive and anxiety
      symptoms influence the relationship between the TCI dimensions and positive and
      negative PLEs. Self-transcendence, persistence, novelty-seeking and self
      directedness significantly predicted positive PLEs; self-directedness and harm
      avoidance were predictable for negative PLEs. Self-transcendence, self
      directedness, persistence and harm avoidance also predicted the distress caused
      by positive PLEs, whereas self-directedness and harm avoidance predicted distress
      raised by negative PLEs. Depressive symptoms and the state of anxiety partially
      mediated the linkage between self-directedness and positive PLEs, and between
      self-directedness, harm avoidance and negative PLEs. Our findings confirm that
      the personality pattern influences both positive and negative PLEs as well as
      distress caused by experiencing positive and negative PLEs, and they indicate
      that certain personality traits may influence the development of PLEs via the
      emotional pathway of heightened depression and anxiety.

PMID- 27718470
TI  - Antagonizing STAT3 activation with benzo[b]thiophene 1, 1-dioxide based small
      molecules.
AB  - STAT3 is an attractive therapeutic target for cancer therapy. However, due to low
      potency or poor druggability, none of its inhibitors are clinically available.
      Herein, a series of aminobenzo[b]thiophene 1, 1-dioxides with good drug-likeness
      properties were designed, synthesized and evaluated as STAT3 inhibitors. Most of
      them exhibited higher antitumor activity than the small-molecule STAT3 inhibitor,
      Stattic. Compound 15 was the most potent and had an IC50 range in 0.33-0.75 MUM
      in various cancer cell lines. The overexpressed and IL-6 induced phosphorylation
      levels of STAT3 were both inhibited by 15 without influencing the phosphorylation
      levels of the upstream kinases Src and Jak2. 15 also suppressed the expressions
      of STAT3 downstream gene, Bcl-2. 15 effectively increased the ROS levels of
      cancer cells, induced cancer cell apoptosis and abolished the colony formation
      ability of cancer cells without affecting bypass kinase p-Erk. Furthermore, 15in
      vivo induced significant antitumor responses, and exhibited less toxicity than
      Doxorubicin. Together, this study described a class of new STAT3 inhibitors as
      antitumor agents.

PMID- 27718471
TI  - Pyrazole derived ultra-short antimicrobial peptidomimetics with potent anti
      biofilm activity.
AB  - In this study, we report on the first chemical synthesis of ultra-short pyrazole
      arginine based antimicrobial peptidomimetics derived from the newly synthesized N
      alkyl/aryl pyrazole amino acids. Through the systematic tuning of hydrophobicity,
      charge, and peptide length, we identified the shortest peptide Py11 with the most
      potent antimicrobial activity. Py11 displayed greater antimicrobial activity
      against antibiotic-resistant bacteria, including MRSA, MDRPA, and VREF, which was
      approximately 2-4 times higher than that of melittin. Besides its higher
      selectivity (therapeutic index) toward bacterial cells than LL-37, Py11 showed
      highly increased proteolytic stability against trypsin digestion and maintained
      its antimicrobial activity in the presence of physiological salts. Interestingly,
      Py11 exhibited higher anti-biofilm activity against MDRPA compared to LL-37. The
      results from fluorescence spectroscopy and transmission electron microscopy (TEM)
      suggested that Py11 kills bacterial cells possibly by integrity disruption
      damaging the cell membrane, leading to the cytosol leakage and eventual cell
      lysis. Furthermore, Py11 displayed significant anti-inflammatory (endotoxin
      neutralizing) activity by inhibiting LPS-induced production of nitric oxide (NO)
      and TNF-alpha. Collectively, our results suggest that Py11 may serve as a model
      compound for the design of antimicrobial and antisepsis agents.

PMID- 27718472
TI  - Discovery of nanomolar ligands with novel scaffolds for the histamine H4 receptor
      by virtual screening.
AB  - The involvement of histamine H4 receptor (H4R) in immune cells chemotaxis and
      mediator release makes it an attractive target for the treatment of inflammation
      disorders. A decade of medicinal chemistry efforts has led to several promising
      ligands, although the chemical structures described so far possesses a singular
      limited diversity. We report here the discovery of novel structures, belonging to
      completely different scaffolds. The virtual screening was planed as a two-steps
      process. First, using a "scout screening" methodology, we have experimentally
      probed the H4R ligand binding site using a small size chemical library with very
      diverse structures, and identified a hit that further assist us in refining a raw
      3D homology model. Second, the refined 3D model was used to conduct a widened
      virtual screening. This two-steps strategy proved to be very successful, both in
      terms of structural diversity and hit rate (23%). Moreover, the hits have high
      affinity for the H4R, with most potent ligands in the nanomolar range.

PMID- 27718473
TI  - Synthesis and anti-mitotic activity of 6,7-dihydro-4H-isothiazolo[4,5-b]pyridin-5
      ones: In vivo and cell-based studies.
AB  - A series of 3,7-diaryl-6,7-dihydroisothiazolo [4,5-b]pyridin-5(4H)-ones 8 and 9
      was synthesized by multicomponent condensation of 3-aryl-5-isothiazolecarboxylic
      acid esters 4a-f with aromatic (or thienyl) aldehydes 7 and Meldrum's acid in an
      acidic medium. The targeted compounds were evaluated for their antimitotic
      microtubule destabilizing activity using in vivo phenotypic sea urchin embryo
      model and in vitro human cancer cell-based assays. Selected
      dihydroisothiazolopyridinones altered sea urchin egg cleavage in 2-10 nM
      concentrations together with significant cytotoxicity against cancer cells
      including chemoresistant cell lines (IC50 in submicromolar - low nanomolar
      concentration range). Both approaches confirmed antimitotic microtubule
      destabilizing mechanism of action of the izothiazole derivatives. Structure
      activity relationship study determined the importance of p-methoxybenzene A-ring
      for the antiproliferative effect. The most potent compound 9b containing p
      methoxybenzene A-ring and thiophene B-ring caused mitotic arrest and
      disintegration of cell microtubules.

PMID- 27718474
TI  - Synthesis and evaluation of N-substituted 2-amino-4,5-diarylpyrimidines as
      selective adenosine A1 receptor antagonists.
AB  - We report the synthesis and biological evaluation of new 2-amino-4,5
      diarylpyrimidines as selective antagonists at the adenosine A1 receptor. The
      scaffold they are based upon is a deaza variation of a previously reported
      collection of 3-amino-5,6-diaryl-1,2,4-triazines, members of which had a
      subnanomolar affinity but limited selectivity over the A2A subtype. Initially,
      similar structure-affinity relationships at the 5-aryl ring were established, and
      then emphasis was put on increasing selectivity at the hA1AR by introducing
      substituents on the N2-position, all the while maintaining a nanomolar affinity.
      Compound 3z, bearing a trans 4-hydroxycyclohexyl substituent, was identified as a
      potent (Ki(hA1AR) = 7.7 nM) and selective (Ki(hA2AAR) = 1389 nM) antagonist at
      the human adenosine A1 receptor. Computational docking was effected at the A1 and
      A2A subtypes, rationalizing the effect of the 4-hydroxycyclohexyl substituent on
      selectivity, in relation with the nature of the substituent on the 5-position of
      the pyrimidine.

PMID- 27718475
TI  - Influence of the dominance of must fermentation by Torulaspora delbrueckii on the
      malolactic fermentation and organoleptic quality of red table wine.
AB  - Torulaspora delbrueckii can improve wine aroma complexity, but its impact on wine
      quality is still far from being satisfactory at the winery level, mainly because
      it is easily replaced by S. cerevisiae yeasts during must fermentation. New T.
      delbrueckii killer strains were selected to overcome this problem. These strains
      killed S. cerevisiae yeasts and dominated fermentation better than T. delbrueckii
      non-killer strains when they were single-inoculated into crushed red grape must.
      All the T. delbrueckii wines, but none of the S. cerevisiae wines, underwent
      malolactic fermentation. Putative lactic acid bacteria were always found in the
      T. delbrueckii wines, but none or very few in the S. cerevisiae wines. Malic acid
      degradation was the greatest in the wines inoculated with the killer strains, and
      these strains reached the greatest dominance ratios and had the slowest
      fermentation kinetics. The T. delbrueckii wines had dried-fruit/pastry aromas,
      but low intensities of fresh-fruit aromas. The aroma differences between the T.
      delbrueckii and the S. cerevisiae wines can be explained by the differences that
      were found in the amounts of some fruity aroma compounds such as isoamyl acetate,
      ethyl hexanoate, ethyl octanoate, and some lactones. This T. delbrueckii effect
      significantly raised the organoleptic quality scores of full-bodied Cabernet
      Sauvignon red wines inoculated with the killer strains. In particular, these
      wines were judged as having excellent aroma complexity, mouth-feel, and
      sweetness.

PMID- 27718476
TI  - Development of visual peak selection system based on multi-ISs normalization
      algorithm to apply to methamphetamine impurity profiling.
AB  - The aim of this study is to improve resolution of impurity peaks using a newly
      devised normalization algorithm for multi-internal standards (ISs) and to
      describe a visual peak selection system (VPSS) for efficient support of impurity
      profiling. Drug trafficking routes, location of manufacture, or synthetic route
      can be identified from impurities in seized drugs. In the analysis of impurities,
      different chromatogram profiles are obtained from gas chromatography and used to
      examine similarities between drug samples. The data processing method using
      relative retention time (RRT) calculated by a single internal standard is not
      preferred when many internal standards are used and many chromatographic peaks
      present because of the risk of overlapping between peaks and difficulty in
      classifying impurities. In this study, impurities in methamphetamine (MA) were
      extracted by liquid-liquid extraction (LLE) method using ethylacetate containing
      4 internal standards and analyzed by gas chromatography-flame ionization
      detection (GC-FID). The newly developed VPSS consists of an input module, a
      conversion module, and a detection module. The input module imports chromatograms
      collected from GC and performs preprocessing, which is converted with a
      normalization algorithm in the conversion module, and finally the detection
      module detects the impurities in MA samples using a visualized zoning user
      interface. The normalization algorithm in the conversion module was used to
      convert the raw data from GC-FID. The VPSS with the built-in normalization
      algorithm can effectively detect different impurities in samples even in complex
      matrices and has high resolution keeping the time sequence of chromatographic
      peaks the same as that of the RRT method. The system can widen a full range of
      chromatograms so that the peaks of impurities were better aligned for easy
      separation and classification. The resolution, accuracy, and speed of impurity
      profiling showed remarkable improvement.

PMID- 27718477
TI  - Pregnant women's cognitive appraisal of a natural disaster affects their
      children's BMI and central adiposity via DNA methylation: Project Ice Storm.
AB  - We determined the extent to which DNA methylation mediates the effects of
      maternal cognitive appraisal of a natural disaster during pregnancy on offspring
      growth at age 13. Negative maternal cognitive appraisal predicted both lower BMI
      and central adiposity via DNA methylation of diabetes-related genes, suggesting a
      protective role of epigenetics.

PMID- 27718478
TI  - An experimental study of shear-dependent human platelet adhesion and underlying
      protein-binding mechanisms in a cylindrical Couette system.
AB  - Undesirable thrombotic reactions count among the most frequent and serious
      complications for patients who rely on the use of medical devices. To improve the
      design of medical devices, it is essential to develop a more precise
      understanding of platelet reactions. Clinical studies and experiments have shown
      a strong dependence of platelet deposition behavior on the flow. However, today
      the influence of hemodynamic parameters such as the shear rate on thrombotic
      reactions is not well understood. For the study of the shear-dependent mechanisms
      leading to the activation, adhesion and aggregation of platelets, a Couette flow
      system was used to investigate thrombocyte behavior with regard to well-defined
      flow conditions at shear-rate values between gamma=400 $?dot ?gamma = {?rm{400}}$
      and 1400 1/s. Results were calculated for physiological temperature. It could be
      shown that the platelet adhesion density increased with increasing shear rates up
      to gamma=800 1/s $?dot ?gamma = {?rm{800 1/s}}$ and the adhesion pattern was
      homogeneous. At gamma=800 1/s, $?dot ?gamma = {?rm{800 1/s}},$ a sudden drop in
      platelet adhesion density occurred and platelets adhered in filaments.
      Fluorescence microscopy results of von Willebrand factor (vWF) confirm that a
      shear rate of gamma=800 1/s $?dot ?gamma = {?rm{800 1/s}}$ represents the
      threshold where a switch of the platelet-binding mechanism from fibrinogen
      mediated to vWF-mediated platelet adhesion takes place.

PMID- 27718479
TI  - Fabrication of multifunctional CaP-TC composite coatings and the corrosion
      protection they provide for magnesium alloys.
AB  - Two major problems with magnesium (Mg) alloy biomaterials are the poor corrosion
      resistance and infection associated with implantation. In this study, a novel
      calcium phosphate (CaP)/tetracycline (TC) composite coating for Mg implants that
      can both improve the corrosion resistance of Mg and release a drug in a durable
      way is reported. Scanning electron microscope (SEM) images showed that TC
      additives make the CaP coating more compact and uniform. Electrochemical tests
      indicated CaP/TC coatings can provide excellent corrosion protection for Mg alloy
      substrates. Besides, TC additives can also provide effective prevention of bone
      infection and inflammation due to its broad-spectrum antibacterial properties.
      The one-step hydrothermal process reported here greatly simplified the multi-step
      fabrication of smart coatings reported previously.

PMID- 27718480
TI  - Can non-cholesterol sterols and lipoprotein subclasses distribution predict
      different patterns of cholesterol metabolism and statin therapy response?
AB  - BACKGROUND: Cholesterol homeostasis disorders may cause dyslipidemia,
      atherosclerosis progression and coronary artery disease (CAD) development.
      Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers,
      and lipoprotein particles quality may indicate the dyslipidemia early
      development. This study investigates associations of different cholesterol
      homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL)
      subclasses distribution in statin-treated and statin-untreated CAD patients, and
      potential use of aforementioned markers for CAD treatment optimization. METHODS:
      The study included 78 CAD patients (47 statin-untreated and 31 statin-treated)
      and 31 controls (CG). NCSs concentrations were quantified using gas
      chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were
      separated by gradient gel electrophoresis. RESULTS: In patients, cholesterol
      synthesis markers were significantly higher comparing to CG. Cholesterol
      synthesis markers were inversely associated with LDL size in all groups. For
      cholesterol homeostasis estimation, each group was divided to good and/or poor
      synthetizers and/or absorbers according to desmosterol and beta-sitosterol median
      values. In CG, participants with reduced cholesterol absorption, the relative
      proportion of small, dense LDL was higher in those with increased cholesterol
      synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was
      significantly higher in poor synthetizers/poor absorbers subgroup compared to
      poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers
      (p<0.01). Statin-treated patients with increased cholesterol absorption had
      increased proportion of LDL IVB (p<0.05). CONCLUSIONS: The results suggest the
      existence of different lipoprotein abnormalities according to various patterns of
      cholesterol homeostasis. Desmosterol/beta-sitosterol ratio could be used for
      estimating individual propensity toward dyslipidemia development and direct the
      future treatment.

PMID- 27718481
TI  - Evaluation of the trueness of serum alkaline phosphatase measurement in a group
      of Italian laboratories.

PMID- 27718482
TI  - Biotin interference in immunoassays mimicking subclinical Graves' disease and
      hyperestrogenism: a case series.

PMID- 27718483
TI  - Lyophilized hemoglobin E control material for the dichlorophenol-indophenol
      (DCIP) test.

PMID- 27718484
TI  - Progress and impact of enzyme measurement standardization.
AB  - International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has
      established reference measurement procedures (RMPs) for the most popular enzymes.
      Manufacturers should assign values to commercial calibrators traceable to these
      RMPs to achieve equivalent results in clinical samples, independent of reagent
      kits, instruments, and laboratory where the measurement is carried out. The
      situation is, however, far from acceptable. Some manufacturers continue to market
      assays giving results that are not traceable to internationally accepted RMPs.
      Meanwhile, end-users often do not abandon assays with demonstrated insufficient
      quality. Of the enzyme measurements, creatine kinase (CK) is satisfactorily
      standardized and a substantial improvement in performance of marketed gamma
      glutamyltranspeptidase (GGT) assays has been demonstrated. Conversely,
      aminotransferase measurements often exceed the desirable analytical performance
      because of the lack of pyridoxal-5-phosphate addition in the commercial reagents.
      Measurements of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and
      alpha-amylase (AMY) still show major disagreement, suggesting the need for
      improvement in implementing traceability to higher-order references. This is
      mainly the result of using assays with different analytical selectivities for
      these enzymes. The definition by laboratory professionals of the clinically
      acceptable measurement uncertainty for each enzyme together with the adoption by
      EQAS of commutable materials and use of an evaluation approach based on trueness
      represent the way forward for reaching standardization in clinical enzymology.

PMID- 27718485
TI  - Quantification of daratumumab in the serum protein electrophoresis.

PMID- 27718486
TI  - Preliminary study in specific activity of molecular components in allergy:
      implications for diagnostics and relationship with disease severity.

PMID- 27718487
TI  - Procalcitonin variation before and after 100-km ultramarathon.

PMID- 27718488
TI  - Biomarkers, inflammation and cancer: where to go?

PMID- 27718489
TI  - Targeting errors in microbiology: the case of the Gram stain.

PMID- 27718490
TI  - Improvement of the chemical inhibition phenotyping assay by cross-reactivity
      correction.
AB  - BACKGROUND: The fraction of an absorbed drug metabolized by the different hepatic
      cytochrome P450 (CYP) enzymes, relative to total hepatic CYP metabolism (fmCYP),
      can be estimated by measuring the inhibitory effects of presumably selective CYP
      inhibitors on the intrinsic metabolic clearance of a drug using human liver
      microsomes. However, the chemical inhibition data are often affected by cross
      reactivities of the chemical inhibitors used in this assay. METHODS: To overcome
      this drawback, the cross-reactivities exhibited by six chemical inhibitors
      (furafylline, montelukast, sulfaphenazole, ticlopidine, quinidine and
      ketoconazole) were quantified using specific CYP enzyme marker reactions. The
      determined cross-reactivities were used to correct the in vitro fmCYPs of nine
      marketed drugs. The corrected values were compared with reference data obtained
      by physiologically based pharmacokinetics simulation using the software SimCYP.
      RESULTS: Uncorrected in vitro fmCYPs of the nine drugs showed poor linear
      correlation with their reference data (R2=0.443). Correction by factoring in
      inhibitor cross-reactivities significantly improved the correlation (R2=0.736).
      CONCLUSIONS: Correcting in vitro chemical inhibition results for cross
      reactivities appear to offer a straightforward and easily adoptable approach to
      provide improved fmCYP data for a drug.

PMID- 27718492
TI  - Efficacy of growth hormone therapy in Kearns-Sayre syndrome: the KIGS experience.
AB  - Kearns-Sayre syndrome (KSS) is characterized by external ophthalmoplegia, retinal
      pigmentation and cardiac conduction defects due to mitochondrial DNA (mtDNA)
      deletions. Short stature and growth hormone (GH) deficiency have been reported in
      KSS, but data on GH treatment is limited. We describe the clinical presentation,
      phenotype evolution, and response to GH in a patient with KSS and report data on
      eight additional KSS patients from the KIGS database. Our patient with KSS and GH
      deficiency achieved a final adult height at -0.8 SDS. In the KIGS database GH
      treatment resulted in mean improvement in height from -3.9 to -2.9 SDS in
      patients with KSS. Two patients did not show growth improvement. Our data shows
      improvement in height SDS in our patient and mixed results in eight additional
      patients from the KIGS database after treatment with GH. Heterogeneity in
      responsiveness may relate to presence of GH deficiency or severity of underlying
      mitochondrial dysfunction.

PMID- 27718491
TI  - A 10-year experience using combined lipid-lowering pharmacotherapy in children
      and adolescents.
AB  - BACKGROUND: Current pediatric guidelines for heterozygous familial
      hypercholesterolemia (HeFH) propose pharmacotherapy (PT) with statins from age 8
      to 10 years; however, schemes with absorption inhibitors combined with statins,
      could be started earlier. The aim of the study was to show the 10-year results of
      a combined treatment protocol. METHODS: Prospective, descriptive and analytical
      study. Pediatric patients (n=70; mean age at PT initiation 9.3 years [range, 2
      17.5]) with HeFH who required PT between 2005 and 2015 were included. All
      patients >=10 years, with LDL >190 mg/dL or >160 mg/dL with one cardiovascular
      risk factor (CVRF) or >130 mg/dL with two or more CVRF; and those patients 5-10
      years and with LDL-C >240 mg/dL or a family history of a cardiovascular event
      before 40 years, were medicated. After a period on a lipid-lowering diet (LLD),
      all patients were started on ezetimibe. Patients who did not achieve the
      treatment goal were given statins. The variables were: age, age at PT initiation,
      duration of PT, initial LDL-C, mean LDL-C during ezetimibe monodrug therapy, mean
      LDL-C during combined PT, and percentage of LDL decrease. RESULTS: LDL-C levels
      were: Baseline: 235 mg/dL+/-55; after 3 months on ezetimibe: 167 mg/dL+/-47
      (decrease: -27.62%). In 18 patients who did not reach the treatment goal
      atorvastatin was added and their LDL-C decreased -41.5% (p: 0.02). Overall, mean
      final LDL-C was 155 mg/dL+/-30.4 (range, 98-257) and treatment goals were reached
      in 74% of the patients. No severe side effects were reported. CONCLUSIONS:
      Combined and sequential treatment starting at early ages was shown to be safe and
      effective over this follow-up period.

PMID- 27718493
TI  - Diagnostic accuracy of fetal scalp lactate for intrapartum acidosis compared with
      scalp pH.
AB  - OBJECTIVE: To determine the diagnostic accuracy of fetal scalp lactate sampling
      (FSLS) and to establish an optimal cut-off value for intrapartum acidosis
      compared with fetal scalp pH. METHODS: A 20-month retrospective cohort study was
      conducted of all neonates delivered in our institution for whom fetal scalp blood
      sampling (FSBS) was performed, matching their intrapartum gasometry to their cord
      gasometry at delivery (n=243). The time taken from the performance of scalp blood
      sampling to arterial umbilical cord gas acquisition was 45 min at most. Five
      arterial cord gasometry patterns were set for assessing the predictive ability of
      both techniques. Subsequent obstetric management for a pathological value was
      analysed considering the use of both techniques. RESULTS: The optimal cut-off
      value for FSLS was 4.8 mmol/L: this value has 100% sensitivity and 63%
      specificity for umbilical arterial cord gas pH<=7.0 and base deficit (BD)>=12
      detection, and 100% sensitivity and 64% specificity for umbilical arterial cord
      gas pH<=7.10 and BD>=12 detection, with a false negative rate of <1.3%, improving
      fetal scalp pH performance. FSLS showed the best area under the curve (AUC) of
      0.86 and 0.84 for both arterial cord gasometry patterns, respectively. Expedite
      birth following lactate criteria would have been the same as following pH
      criteria (92 obstetric interventions) with no cases of missed metabolic acidosis.
      In the cohort, 19.8% of cases were discordant, but no cases of metabolic acidosis
      were in this group. CONCLUSIONS: FSLS improves the detection of metabolic
      acidosis via fetal scalp pH with an optimal cut-off value of 4.8 mmol/L. FSLS can
      be used without increasing obstetrical interventions or missing metabolic
      acidosis.

PMID- 27718494
TI  - The value of ultrasound measurement of cervical length and parity in prediction
      of cesarean section risk in term premature rupture of membranes and unfavorable
      cervix.
AB  - AIM: To evaluate the influence of cervical length (CL) and parity as prediction
      factors for assessment of cesarean section (CS) risk in women with premature
      rupture of membranes (PROM) at term and unfavorable cervix, undergoing induction
      of labor (IOL) with dinoprostone intracervical gel. METHODS: A prospective study
      involved 50 nulliparous and 51 multiparous women admitted for IOL. Pre-induction
      CL was measured and delivery outcomes were recorded. RESULTS: Nulliparous women
      were younger than the multiparous (26.6+/-5.2 vs. 30.5+/-4.9; P<0.001) and had
      longer pre-induction CL (35.6+/-5.5 vs. 31.5+/-4.8; P<0.001) and induction
      delivery interval (582 vs. 420 min; P<0.001). There was no difference in the mode
      of delivery, CS indications, Apgar score, neonatal weight, the rate of neonatal
      intensive care unit admission and perinatal death in respect of parity. CL was
      significantly shorter in vaginal vs. cesarean deliveries regardless of parity
      (31.4 vs. 38.8 mm, P<0.001, respectively). Cut-off values of CL for predicting CS
      were 37.5 mm in nulliparae and 34.5 mm in multiparae. CONCLUSIONS: CLs of 37.5 mm
      in nulliparae and 34.5 mm in multiparae were determined as the cut-off values in
      predicting CS risk in women with PROM at term and unfavorable cervix.

PMID- 27718495
TI  - Risk of recurrent preterm birth among women according to change in partner.
AB  - There is well-established literature indicating change in partner as a risk for
      preeclampsia, yet the research on the risk of preterm birth after a change in
      partners has been sparse and inconsistent. Using a population of California live
      born singletons, we aimed to determine the risk of preterm birth after a change
      in partner between the first and second pregnancies. The risk of preterm and
      early term delivery in the second pregnancy was calculated for mothers who did or
      did not change partners between births with the referent group as women who
      delivered both pregnancies at term and did not change partners. Adjusted odds
      ratios (ORs) and their 95% confidence intervals (CIs) were calculated. Relative
      to women who delivered at 39 weeks or later in the second pregnancy and did not
      change partners, preterm birth risks were somewhat lower for women who changed
      partners between the first and second pregnancies compared to those women who did
      not change partners. For example, 10.6% of women who did not change partners and
      delivered their second pregnancy before 34 weeks also delivered their first
      pregnancy before 34 weeks, while 8.5% of women who changed partners delivered
      before 34 weeks. Findings suggest partner change may alter the risk of preterm
      birth.

PMID- 27718496
TI  - Effect of acute stress on auditory processing: a systematic review of human
      studies.
AB  - Stress is an integral part of modern life. Although there is a large body of
      literature regarding the harmful effects of chronic stress on different aspects
      of human life, acute stress is the most common form of stress, resulting from the
      demands and pressures of the recent past and the anticipated demands and
      pressures of the near future. In spite of its pervasive nature, less attention
      has been paid to the impact of acute stress on sensory processing than to the
      consequences of chronic stress, particularly concerning auditory processing. In
      this systematic review, the impact of experimental acute stress on the auditory
      processing of healthy adults was investigated. The results revealed the adverse
      effects of acute physical and psychological stresses on auditory processing.
      According to the open field of research on stress and the auditory system and the
      high possibility of experiencing different types of acute stresses in various
      life environments, including testing places, it seems that more investigations
      are needed to identify and manage different types of acute stresses in both
      clinical and research situations.

PMID- 27718497
TI  - The relationship between study strategies and academic performance.
AB  - Objectives: To investigate if and to what extent the Learning and Study Strategy
      Inventory (LASSI) and the Self-Directed Learning Readiness Scale (SDLRS) yield
      academic performance predictors; To examine if LASSI findings are consistent with
      previous research. Methods: Medical school students completed the LASSI and SDLRS
      before their first and second years (n = 168). Correlational and regression
      analyses were used to determine the predictive value of the LASSI and the SDLRS.
      Paired t-tests were used to test if the two measurement points differed.
      Bivariate correlations and R2s were compared with five other relevant studies.
      Results: The SDLRS was moderately correlated with all LASSI subscales in both
      measures (r(152) =.255, p=.001) to (r(152) =.592, p =.000). The first SDLRS, nor
      the first LASSI, were predictive of academic performance. The second LASSI
      measure was a significant predictor of academic performance (R2(138) = 0.188, p =
      .003). Six prior LASSI studies yielded a range of R2s from 10-49%. Conclusions:
      The SDLRS is moderately correlated with all LASSI subscales. However, the
      predictive value of the SDLRS and LASSI differ. The SDLRS does not appear to be
      directly related to academic performance, but LASSI subscales: Concentration,
      Motivation, Time Management, and Test Strategies tend to be correlated. The
      explained LASSI variance ranges from 10% to 49%, indicating a small to
      substantial effect. Utilizing the LASSI to provide medical school students with
      information about their strengths and weaknesses and implementing targeted
      support in specific study strategies may yield positive academic performance
      outcomes.

PMID- 27718498
TI  - The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and
      aldehyde dehydrogenase in the sera of bladder cancer patients.
AB  - OBJECTIVES: Studies on alcohol dehydrogenase (ADH) and aldehyde dehydrogenase
      (ALDH) activity in the sera of patients with malignant neoplasms show that cancer
      cells in many organs may release ADH isoenzymes into the blood. The aim of this
      study was to investigate the differences in the activity of ADH isoenzymes and
      ALDH in the sera of patients with bladder cancer (BCa), and with different grades
      of the disease. MATERIAL AND METHODS: Blood samples were taken from 39 patients
      with BCa (15 patients with low-grade and 24 with high-grade BCa) and from 60
      healthy subjects. Class III and IV of ADH and total ADH activity were measured
      using the photometric method, while class I and II ADH and ALDH activity using
      the fluorometric method with class-specific fluorogenic substrates. RESULTS: The
      activity of the class I ADH isoenzyme and total ADH was significantly higher in
      the sera of BCa patients as compared to control group. Analysis of ALDH activity
      did not show statistically significant differences between the tested groups.
      Significantly higher total activity of ADH in comparison to control was found in
      both, low-grade and high-grade BCa group. The activity of ADH class I was also
      significantly higher in high-grade BCa group when compared to low-grade patients
      and controls. CONCLUSION: The increase of total ADH activity in the sera of BCa
      patients seems to be caused by isoenzymes released from cancerous cells. The
      higher activity of ADH I probably resulted from metastatic tumors as significant
      increase was detected only in the sera of high-grade bladder cancer patients.

PMID- 27718499
TI  - Amentoflavone prevents sepsis-associated acute lung injury through Nrf2-GCLc
      mediated upregulation of glutathione.
AB  - Sepsis is a serious medical problem and is one of the main causes of high
      mortality in intensive care units. Fifty percent of patients with severe sepsis
      will develop acute lung injury (ALI). Amentoflavone (AMF) is a polyphenolic
      compound possessing potent anti-inflammatory activities. The study aimed to
      explore the protective effects of AMF against ALI in cecal ligation and puncture
      (CLP)-induced septic rats. The results showed that AMF administration protected
      against septic ALI, as reflected by marked amelioration of histological injury of
      lung tissues and decrease of pulmonary edema in CLP-treated rats. AMF ameliorated
      CLP-induced increase of systemic and lung TNFalpha and IL-1beta and binding
      activity of p65 NF-kappaB, indicating the inhibition of inflammation. Moreover,
      AMF prevented CLP-induced oxidative stress, as evidenced by increase of oxygen
      consumption rate, decrease of TBARS content, increase of SOD activity and GSH
      level in lung tissue of CLP-treated rats. CLP resulted in significant decrease of
      mRNA expression of Nrf2 and GCLc, which was inhibited by AMF. AMF-induced
      protective effects on ALI, inflammation, and oxidative stress were inhibited by
      lentivirus shRNA-mediated silence of Nrf2 and buthionine sulphoximine (BSO), an
      inhibitor of GSH synthesis. AMF increased Nrf2-binding activity in GCLc promoters
      in lung tissue of CLP-treated rats. The results suggested that AMF protected
      against ALI in septic rats through upregulation of Nrf2-GCLc signaling,
      enhancement of GSH antioxidant defense, reduction of oxidative stress and final
      amelioration of inflammation and histological injury of lung. The data provide
      new therapeutic options for the treatment of sepsis-associated ALI.

PMID- 27718500
TI  - Patients with lichen sclerosus experience moderate satisfaction with treatment
      and impairment of quality of life: results of a cross-sectional study.
AB  - BACKGROUND: Although they are considered relevant, little is known about
      satisfaction with treatment and health-related quality of life (HRQoL) among
      patients with lichen sclerosus (LS). OBJECTIVES: In a cross-sectional study, we
      aimed to examine (i) satisfaction with treatment, (ii) patient characteristics
      associated with satisfaction and (iii) HRQoL in Dutch patients with LS. METHODS:
      Members of the Dutch LS Patient Association (n = 750) were invited to complete a
      web-based survey. We measured satisfaction with treatment with a study-specific
      questionnaire, and HRQoL with the Skindex-29. We calculated domain scores for
      symptoms, emotions and functioning, and categorized scores into little, mildly,
      moderately or severely impaired HRQoL. We used a multiple linear regression
      analysis to examine whether patient characteristics were associated with
      treatment satisfaction. RESULTS: In total 303 patients (40.4%) were included.
      Patients under current treatment (n = 265, 87.5%) were moderately satisfied with
      their treatment. Patients rated 'treatment effectiveness' as most important,
      although 58 (22%) were dissatisfied with the effectiveness of their current
      treatment. More impairment on the HRQoL emotions domain and a higher degree of
      disease severity were both associated with lower satisfaction with treatment and
      explained in total 13.5% of the variance in treatment satisfaction. On all HRQoL
      domains, one-third of the patients (range 34.7-38.9%) reported severe impairment.
      CONCLUSIONS: Patients with LS are moderately satisfied with their treatment, and
      one-third of patients experience severe impairment of HRQoL. To improve
      dermatological care, we recommend enhancement of doctor-patient communication,
      information provision and organization, which may be more amenable to change than
      treatment effectiveness or safety.

PMID- 27718501
TI  - Progress toward reaction monitoring at variable temperatures: a new stopped-flow
      NMR probe design.
AB  - A stopped-flow NMR probe is described that enables fast flow rates, short
      transfer times, and equilibration of the reactant magnetization and temperature
      prior to reaction. The capabilities of the probe are demonstrated by monitoring
      the polymerization of lactide as catalyzed by the air-sensitive catalyst 1,3
      dimesitylimidazol-2-ylidene (IMes) over the temperature range of -30 to 40 
      degrees C. The incorporation of stopped-flow capabilities into an NMR probe
      permits the rich information content of NMR to be accessed during the first few
      seconds of a fast reaction. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27718502
TI  - Pelvic floor muscle dysfunction on 3D/4D transperineal ultrasound in patients
      with deep infiltrating endometriosis: a pilot study.
AB  - OBJECTIVE: Pelvic floor muscle (PFM) dysfunction seems to play an important role
      in the pathophysiology of pelvic pain, including that associated with deep
      infiltrating endometriosis (DIE). The aim of this study was to evaluate the
      static and dynamic morphometry of the PFM using three-dimensional (3D) and four
      dimensional (4D) transperineal ultrasound in women with DIE compared with
      asymptomatic healthy women. METHODS: This was a pilot, prospective study
      conducted at our tertiary center between March and November 2015. Fifty
      nulliparous women with DIE (study group) and 35 nulliparous asymptomatic healthy
      women (control group) were included. 3D/4D transperineal ultrasound examination
      of the PFM was performed in both groups. Levator hiatal area (LHA) and
      anteroposterior and left-right transverse diameters were evaluated at rest, on
      maximum PFM contraction and on maximum Valsalva maneuver. Persistent levator ani
      muscle (LAM) coactivation during Valsalva maneuver was investigated. RESULTS:
      Compared with the control group, women with DIE had a smaller LHA at rest (P =
      0.03) and during Valsalva maneuver (P < 0.01). Furthermore, reduction in LHA
      during PFM contraction (P < 0.001) and enlargement in LHA during Valsalva
      maneuver (P = 0.01) were significantly less marked. In comparison with controls,
      women with DIE presented a higher frequency of LAM coactivation during Valsalva
      maneuver, although this difference did not reach statistical significance (P =
      0.05). CONCLUSIONS: 3D and 4D transperineal ultrasound is an objective and non
      invasive method for PFM morphometry and may have a role in detecting PFM
      dysfunction in women with DIE. Copyright (c) 2016 ISUOG. Published by John Wiley
      & Sons Ltd.

PMID- 27718503
TI  - Immunohistochemical analysis of T-type calcium channels in acquired melanocytic
      naevi and melanoma.
AB  - BACKGROUND: Cutaneous malignant melanoma arises from transformed melanocytes de
      novo or from congenital or acquired melanocytic naevi. We have recently reported
      that T-type Ca2+ channels (TT-Cs) are upregulated in human melanoma and play an
      important role in cell proliferation. OBJECTIVES: To describe for the first time
      in formalin-fixed paraffin-embedded tissue the immunoexpression of TT-Cs in
      biopsies of normal skin, acquired melanocytic naevi and melanoma, in order to
      evaluate their role in melanomagenesis and/or tumour progression, their utility
      as prognostic markers and their possible use in targeted therapies. METHODS:
      Tissue samples from normal skin, melanocytic naevi and melanoma were subjected to
      immunohistochemistry for two TT-Cs (Cav3.1, Cav3.2); markers of proliferation
      (Ki67), the cell cycle (cyclin D1), hypoxia (Glut1), vascularization (CD31) and
      autophagy (LC3); BRAF V600E mutation (VE1) and phosphatase and tensin homologue
      (PTEN). Immunostaining was evaluated by histoscore. In silico analysis was used
      to assess the prognostic value of TT-C overexpression. RESULTS: TT-C
      immunoexpression increased gradually from normal skin to common naevi, dysplastic
      naevi and melanoma samples, but with differences in the distribution of both
      isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic
      melanoma than in primary melanoma. Statistical correlation showed a linear
      interaction between PTEN loss/BRAF V600E/Cav3.1/LC3/ Ki67/cyclin D1/Cav3.2/Glut1.
      Disease-free survival (DFS) and overall survival correlated inversely with
      overexpression of Cav3.2. DFS also correlated inversely with overexpression of
      Cav3.1. CONCLUSIONS: TT-C immunoexpression on melanocytic neoplasms is consistent
      with our previous in vitro studies and appears to be related to tumour
      progression. TT-C upregulation can be considered as a prognostic marker using The
      Cancer Genome Atlas database. The high expression of Cav3.2 in metastatic
      melanoma encourages the investigation of the use of TT-C blockers in targeted
      therapies.

PMID- 27718504
TI  - Cancer-and-treatment-specific distress and its impact on posttraumatic stress in
      patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).
AB  - BACKGROUND: In this prospective multicenter study, we investigated cancer-and
      treatment-specific distress (CTXD) and its impact on symptoms of posttraumatic
      stress disorder (PTSD) in patients undergoing allogeneic hematopoietic stem cell
      transplantation (HSCT). METHODS: Patients were consulted before (T0, N = 239), 3
      (T1, N = 150), and 12 months (T2, N = 102) after HSCT. Medical (eg, diagnosis and
      pretreatment) and demographic information, CTXD and PTSD (PCL-C) were assessed.
      RESULTS: Random intercept models revealed that the sum score of CTXD was highest
      pre-HSCT (T0), decreased by T1 (gamma = -.18, 95% CI [-.26/-.09]), and by T2
      (gamma = -.10, 95% CI [-.20/-.00]). Uncertainty, family strain, and health burden
      were rated most distressing during HSCT. Uncertainty and family strain decreased
      from T0 to T1 (gamma = -.30, 95% CI [-.42/-.17]; gamma = -.10, 95% CI [-.20/
      .00]) and health burden from T1 to T2 (gamma = -.21, 95% CI [-.36/.05]). Women
      were more likely to report uncertainty (gamma = .38, 95% CI [.19/.58]), family
      strain (gamma = .38, 95% CI [.19/.58]), and concerns regarding appearance and
      sexuality (gamma = .31, 95% CI [.14/.47]) than men. Uncertainty (gamma = .18, 95%
      CI [.12/.24]), appearance and sexuality (gamma = .09, 95% CI [.01/.16]), and
      health burden (gamma = .21, 95% CI [.14/.27]) emerged as predictors of PTSD
      symptomatology across the 3 assessment points. CONCLUSIONS: Our data provide
      first evidence regarding the course of 6 dimensions of CTXD during HSCT and their
      impact on PTSD symptomatology. Specifically, results emphasize the major burden
      of uncertainty pre-HSCT and the impact of uncertainty and concerns regarding
      appearance and sexuality on PTSD symptomatology.

PMID- 27718505
TI  - Optimization of techniques for multiple platform testing in small, precious
      samples such as human chorionic villus sampling.
AB  - BACKGROUND: Multiple testing to understand global changes in gene expression
      based on genetic and epigenetic modifications is evolving. Chorionic villi,
      obtained for prenatal testing, is limited, but can be used to understand ongoing
      human pregnancies. However, optimal storage, processing and utilization of CVS
      for multiple platform testing have not been established. RESULTS: Leftover CVS
      samples were flash-frozen or preserved in RNAlater. Modifications to standard
      isolation kits were performed to isolate quality DNA and RNA from samples as
      small as 2-5 mg. RNAlater samples had significantly higher RNA yields and quality
      and were successfully used in microarray and RNA-sequencing (RNA-seq). RNA-seq
      libraries generated using 200 versus 800-ng RNA showed similar biological
      coefficients of variation. RNAlater samples had lower DNA yields and quality,
      which improved by heating the elution buffer to 70  degrees C. Purification of
      DNA was not necessary for bisulfite-conversion and genome-wide methylation
      profiling. CVS cells were propagated and continue to express genes found in
      freshly isolated chorionic villi. CONCLUSIONS: CVS samples preserved in RNAlater
      are superior. Our optimized techniques provide specimens for genetic, epigenetic
      and gene expression studies from a single small sample which can be used to
      develop diagnostics and treatments using a systems biology approach in the
      prenatal period. (c) 2016 John Wiley & Sons, Ltd.

PMID- 27718506
TI  - Serial versus single troponin measurements for the prediction of cardiovascular
      events and mortality in stable chronic haemodialysis patients.
AB  - AIM: This study aims to describe the variability of pre-dialysis troponin values
      in stable haemodialysis patients and compare the performance of single versus
      fluctuating or persistently elevated troponins in predicting a composite of
      mortality and cardiac arrest, myocardial infarction or stroke. METHODS: A total
      of 128 stable ambulatory chronic haemodialysis patients were enrolled. Pre
      dialysis troponin I was measured for three consecutive months. The patients were
      followed for 1 year. A troponin elevation (>0.06 MUg/L) was considered high risk,
      and patients were classified into three risk groups: (i) patients who had normal
      troponin levels on all three measurements; (ii) patients with at least one
      elevated and one normal troponin value; and (iii) patients with elevated troponin
      values on all measurements. RESULTS: A total of 81 patients had all three
      troponin values in the normal range; 29 had fluctuating values; 18 had all three
      values elevated. Twenty-seven deaths or composite events were observed: eight in
      the first risk group, 10 in the second and nine in the third. Persistently
      elevated and fluctuating troponin values were associated with higher mortality
      and cardiovascular event rate. Serial troponin measurement had a higher
      sensitivity for the composite outcome than single troponin measurement when
      either fluctuating or persistently elevated values were considered to confer high
      risk. CONCLUSION: Most haemodialysis patients do not have elevated troponin
      levels at baseline. Troponin levels that remain elevated or fluctuate are
      associated with worse outcomes. A serial troponin measurement strategy is
      associated with better sensitivity and higher negative predictive value compared
      with single troponin measurement.

PMID- 27718507
TI  - A resting-state fMRI study of obese females between pre- and postprandial states
      before and after bariatric surgery.
AB  - Past studies utilizing resting-state functional MRI (rsfMRI), have shown that
      obese humans exhibit altered activity in brain areas related to reward compared
      to normal-weight controls. However, to what extent bariatric surgery-induced
      weight loss alters resting-state brain activity in obese humans is less well
      studied. Thus, we measured the fractional amplitude of low-frequency fluctuations
      from eyes-closed, rsfMRI in obese females (n = 11, mean age = 42 years, mean BMI
      = 41 kg/m2 ) in both a pre- and postprandial state at two time points: four weeks
      before, and four weeks after bariatric surgery. Several brain areas showed
      altered resting-state activity following bariatric surgery, including the
      putamen, insula, cingulate, thalamus and frontal regions. Activity augmented by
      surgery was also dependent on prandial state. For example, in the fasted state,
      activity in the middle frontal and pre- and postcentral gyri was found to be
      decreased after surgery. In the sated state, activity within the insula was
      increased before, but not after surgery. Collectively, our results suggest that
      resting-state neural functions are rapidly affected following bariatric surgery
      and the associated weight loss and change in diet.

PMID- 27718508
TI  - Psoriasis, fracture risk and bone mineral density: the HUNT Study, Norway.
AB  - BACKGROUND: An association between psoriasis and osteoporosis has been reported.
      OBJECTIVES: To investigate, in a large prospective population-based Norwegian
      study, whether psoriasis is associated with increased risk of forearm or hip
      fracture; to investigate the cross-sectional association between psoriasis and
      bone mineral density (BMD) T-score in a subpopulation. METHODS: Hospital-derived
      fracture data from Nord-Trondelag County (1995-2013) were linked to psoriasis
      information, BMD measurements and lifestyle factors from the third survey of the
      Nord-Trondelag Health Study 2006-08 (HUNT3); socioeconomic data from the National
      Education Database; and use of medication from the Norwegian Prescription
      Database. RESULTS: Among 48 194 participants in HUNT3, we found no increased risk
      of forearm or hip fracture in 2804 patients with self-reported psoriasis [overall
      age- and sex-adjusted hazard ratio 1.03, 95% confidence interval (CI) 0.82-1.31].
      No clear association was found between psoriasis and mean BMD T-score; overall
      age- and sex-adjusted differences in total hip, femoral neck and lumbar spine BMD
      T-scores were 0.02 (95% CI -0.11 to 0.14), 0.05 (95% CI -0.06 to 0.17) and 0.07
      (95% CI -0.09 to 0.24), respectively. No clear association was found between
      psoriasis and prevalent osteoporosis in either total hip, femoral neck or lumbar
      spine; overall age- and sex-adjusted odds ratio was 0.77 (95% CI 0.54-1.10).
      Associations did not change substantially after adjustment for education,
      smoking, systemic steroid use and body mass index. CONCLUSIONS: We found no
      association between psoriasis and risk of fracture. The study did not indicate
      reduced BMD T-score or higher prevalence of osteoporosis among patients with
      psoriasis.

PMID- 27718509
TI  - Role of Wnt/beta-catenin pathway in the nucleus accumbens in long-term cocaine
      induced neuroplasticity: a possible novel target for addiction treatment.
AB  - Cocaine addiction is a chronic relapsing disorder characterized by the loss of
      control over drug-seeking and taking, and continued drug use regardless of
      adverse consequences. Despite years of research, effective treatments for psycho
      stimulant addiction have not been identified. Persistent vulnerability to relapse
      arises from a number of long-lasting adaptations in the reward circuitry that
      mediate the enduring response to the drug. Recently, we reported that the
      activity of the canonical or Wnt/beta-catenin pathway in the prefrontal cortex
      (PFC) is very important in the early stages of cocaine-induced neuroadaptations.
      In the present work, our main goal was to elucidate the relevance of this pathway
      in cocaine-induced long-term neuroadaptations that may underlie relapse. We found
      that a cocaine challenge, after a period of abstinence, induced an increase in
      the activity of the pathway which is revealed as an increase in the total and
      nuclear levels of beta-catenin (final effector of the pathway) in the nucleus
      accumbens (NAcc), together with a decrease in the activity of glycogen synthase
      kinase 3beta (GSK3beta). Moreover, we found that the pharmacological modulation
      of the activity of the pathway has long-term effects on the cocaine-induced
      neuroplasticity at behavioral and molecular levels. All the results imply that
      changes in the Wnt/beta-catenin pathway effectors are long-term neuroadaptations
      necessary for the behavioral response to cocaine. Even though more research is
      needed, the present results introduce the Wnt canonical pathway as a possible
      target to manage cocaine long-term neuroadaptations.

PMID- 27718510
TI  - Mechanomyographic responses during recruitment curves in the soleus muscle.
AB  - INTRODUCTION: In this study we examined relationships among mechanomyographic
      (MMG), electromyographic (EMG), and peak twitch torque (PTT) responses as well as
      test-retest reliability when recorded during recruitment curves in the soleus
      muscle. METHODS: PTT, EMG (M-wave, H-reflex), and MMG responses were recorded
      during recruitment curves in 16 subjects (age 24 +/- 2 years) on 2 separate days.
      The sum of the M-wave and H-reflex (M+H) was calculated. Correlations among
      variables and test-retest reliability were determined. RESULTS: MMG was
      correlated with PTT (mean r = 0.93, range r = 0.59-0.99), the M-wave (0.95, 0.04
      0.98), and M+H (0.91, 0.42-0.97), but was unrelated to the H-reflex (-0.06, -0.56
      to 0.47). Reliability was consistently high among most variables, but normalizing
      to the maximum value improved MMG reliability and the minimum detectable change.
      CONCLUSION: MMG responses predicted 86%-90% of the variability in PTT, M-wave,
      and M+H; thus, MMG may be a useful alternative for estimating twitch torque and
      maximal activation. Muscle Nerve 56: 107-116, 2017.

PMID- 27718511
TI  - Oral probiotic treatment of Lactobacillus rhamnosus Lcr35(r) prevents visceral
      hypersensitivity to a colonic inflammation and an acute psychological stress.
AB  - AIMS: This study evaluated the efficacy of a repeated oral treatment with two
      active pharmaceutical ingredients (Lcr Lenio(r) and Lcr Restituo(r) ) derivated
      from the probiotic bacterial strain Lactobacillus rhamnosus Lcr35(r) in two
      animal models mimicking different features of irritable bowel syndrome (IBS). IBS
      is characterized by visceral pain associated with alteration of bowel transit.
      IBS patients present visceral hypersensitivity with peripheral and central
      origins. METHODS AND RESULTS: The injection of 2,4,6-trinitrobenzenesulfonic acid
      (TNBS) into the proximal colon as well as an acute partial restraint stress (PRS)
      produces colonic hypersensitivity measured in conscious rats by a decrease in
      pain threshold in response to distal colonic distension. Visceral
      hypersensitivity was produced by injection of TNBS 7 days before colonic
      distension or by acute PRS on testing day. Treatments were performed once a day
      during eight consecutive days. CONCLUSIONS: This study indicates that an 8-day
      probiotic treatment (Lcr Lenio and Lcr Restituo) produces an antihypersensitivity
      activity in both TNBS and PRS visceral pain models. As this probiotic strain
      attenuates peripherally and centrally induced visceral hypersensitivity in rats,
      it may be active in treatment of IBS symptoms. An immunomodulatory effect of the
      probiotics was highlighted in the TNBS model on the IL-23 secretion, suggesting a
      mechanism of action involving a regulation of the local IL-23/Th17 immune
      activation. SIGNIFICANCE AND IMPACT OF THE STUDY: Two formulas of Lcr35(r)
      probiotic strain show very encouraging results for the treatment of IBS patients.
      Further studies are needed to better understand the role and mechanisms of
      probiotics on the pathogenesis of IBS.

PMID- 27718513
TI  - Effects of ocean acidification increase embryonic sensitivity to thermal extremes
      in Atlantic cod, Gadus morhua.
AB  - Thermal tolerance windows serve as a powerful tool for estimating the
      vulnerability of marine species and their life stages to increasing temperature
      means and extremes. However, it remains uncertain to which extent additional
      drivers, such as ocean acidification, modify organismal responses to temperature.
      This study investigated the effects of CO2 -driven ocean acidification on
      embryonic thermal sensitivity and performance in Atlantic cod, Gadus morhua, from
      the Kattegat. Fertilized eggs were exposed to factorial combinations of two PCO2
      conditions (400 MUatm vs. 1100 MUatm) and five temperature treatments (0, 3, 6, 9
      and 12  degrees C), which allow identifying both lower and upper thermal
      tolerance thresholds. We quantified hatching success, oxygen consumption (MO2 )
      and mitochondrial functioning of embryos as well as larval morphometrics at hatch
      and the abundance of acid-base-relevant ionocytes on the yolk sac epithelium of
      newly hatched larvae. Hatching success was high under ambient spawning conditions
      (3-6  degrees C), but decreased towards both cold and warm temperature extremes.
      Elevated PCO2 caused a significant decrease in hatching success, particularly at
      cold (3 and 0  degrees C) and warm (12  degrees C) temperatures. Warming imposed
      limitations to MO2 and mitochondrial capacities. Elevated PCO2 stimulated MO2 at
      cold and intermediate temperatures, but exacerbated warming-induced constraints
      on MO2 , indicating a synergistic interaction with temperature. Mitochondrial
      functioning was not affected by PCO2 . Increased MO2 in response to elevated PCO2
      was paralleled by reduced larval size at hatch. Finally, ionocyte abundance
      decreased with increasing temperature, but did not differ between PCO2
      treatments. Our results demonstrate increased thermal sensitivity of cod embryos
      under future PCO2 conditions and suggest that acclimation to elevated PCO2
      requires reallocation of limited resources at the expense of embryonic growth. We
      conclude that ocean acidification constrains the thermal performance window of
      embryos, which has important implication for the susceptibility of cod to
      projected climate change.

PMID- 27718514
TI  - Elevated IL-17A and IL-22 regulate expression of inducible CD38 and Zap-70 in
      chronic lymphocytic leukemia.
AB  - BACKGROUND: In this study, we investigated the role and expression of interleukin
      (IL)-17A and IL-22 in chronic lymphocytic leukemia. METHODS: We evaluated the
      expression of markers above on CLL by ELISA, qRT-PCR, flow cytometric analysis
      and nonparametric Kruskal-Wallis test. RESULTS: Quantitative RT-PCR revealed that
      the mRNA levels of IL-17A and IL-22 in PBMCs of CLL patients were upregulated
      compared with those from healthy subjects (mean +/- SD: 1.96 +/- 0.232 vs.0.72 +/
      0.15, P < 0.001 and mean +/- SD: 2.45 +/- 0.534 vs.0.81 +/- 0.26, P < 0.001,
      respectivily). In addition, findings showed that the IL-17A and IL-22 plasma
      level was significantly elevated than that from healthy control group (P  <
      0.001). The median IL-17A and IL-22 in CLL patients and healthy control group
      were 48.28 +/- 17.2 pg mL-1 ; 20.01 +/- 11.16 pg mL-1 and 58.68 +/- 23.4 pg mL-1
      ;16.47 +/- 10.31 P < 0.001, respectively. The levels of IL-17A and IL-22 was not
      significantly associated with the different stages of disease (Rai stages;
      Kruskal-Wallis test P > 0.05).No significant relationship was found between
      expression of CD38 and higher median serum levels of IL-17A in patients, but
      patients with negative expression of ZAP-70 showed a significant association with
      higher median serum levels of IL-17A compared with healthy subjects. (57.84 pg mL
      1 vs. 31.67 pg mL-1 ; P = 0.016). CONCLUSION: IL-22 is elevated and associated
      with CD38 and Zap-70 expression in patients with CLL. No significant correlation
      was found between expression of CD38 and increased levels of IL-17A, negative
      expression of ZAP-70 showed a significant association with increased levels of IL
      17A. (c) 2016 International Clinical Cytometry Society.

PMID- 27718512
TI  - Feasibility and tolerability of whole-body, low-intensity vibration and its
      effects on muscle function and bone in patients with dystrophinopathies: a pilot
      study.
AB  - INTRODUCTION: Dystrophinopathies are X-linked muscle degenerative disorders that
      result in progressive muscle weakness complicated by bone loss. This study's goal
      was to evaluate feasibility and tolerability of whole-body, low-intensity
      vibration (WBLIV) and its potential effects on muscle and bone in patients with
      Duchenne or Becker muscular dystrophy. METHODS: This 12-month pilot study
      included 5 patients (age 5.9-21.7 years) who used a low-intensity Marodyne LivMD
      plate vibrating at 30-90 Hz for 10 min/day for the first 6 months. Timed motor
      function tests, myometry, and peripheral quantitative computed tomography were
      performed at baseline and at 6 and 12 months. RESULTS: Motor function and lower
      extremity muscle strength remained either unchanged or improved during the
      intervention phase, followed by deterioration after WBLIV discontinuation.
      Indices of bone density and geometry remained stable in the tibia. CONCLUSIONS:
      WBLIV was well tolerated and appeared to have a stabilizing effect on lower
      extremity muscle function and bone measures. Muscle Nerve 55: 875-883, 2017.

PMID- 27718515
TI  - Effect of a general practitioner management plan on health outcomes and
      hospitalisations in older patients with diabetes.
AB  - BACKGROUND: Little is known about the impact of a general practitioner management
      plan (GPMP) on health outcomes of patients with diabetes. AIM: To examine the
      impact of a GPMP on the risk of hospitalisation for diabetes. METHODS: A
      retrospective study using administrative data from the Australian Government
      Department of Veterans' Affairs was conducted (1 July 2006 to 30 June 2014) of
      diabetes patients either exposed or unexposed to a GPMP. The primary end-point
      was the risk of first hospitalisation for a diabetes-related complication and was
      assessed using Cox proportional hazard regression models with death as a
      competing risk. Secondary end-points included rates of receiving guideline care
      for diabetes, with differences assessed using Poisson regression analyses.
      RESULTS: A total of 16 214 patients with diabetes were included; 8091 had a GPMP,
      and 8123 did not. After 1 year, 545 (6.7%) patients with a GPMP and 634 (7.8%) of
      patients without a GPMP were hospitalised for a diabetes complication. There was
      a 22% reduction in the risk of being hospitalised for a diabetes complication
      (adjusted hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.87, P <
      0.0001) for those who received a GPMP by comparison to those who did not.
      Increased rates of diabetes guideline care, HbA1c claims (adjusted HR 1.29, 95%
      CI 1.25-1.33) and microalbuminura claims (adjusted HR 1.65, 95% CI 1.58-1.72)
      were observed after a GPMP. CONCLUSION: Provision of a GPMP in older patients
      with diabetes resulted in improved health outcomes, delaying the risk of
      hospitalisation at 12 months for diabetes complications. GPMP should be included
      as part of routine primary care for older patients with diabetes.

PMID- 27718516
TI  - Loss of the arginine methyltranserase PRMT7 causes syndromic intellectual
      disability with microcephaly and brachydactyly.
AB  - Post-translational protein modifications exponentially expand the functional
      complement of proteins encoded by the human genome. One such modification is the
      covalent addition of a methyl group to arginine or lysine residues, which is used
      to regulate a substantial proportion of the proteome. Arginine and lysine
      methylation are catalyzed by protein arginine methyltransferase (PRMTs) and
      protein lysine methyltransferase proteins (PKMTs), respectively; each
      methyltransferase has a specific set of target substrates. Here, we report a male
      with severe intellectual disability, facial dysmorphism, microcephaly, short
      stature, brachydactyly, cryptorchidism and seizures who was found to have a
      homozygous 15,309 bp deletion encompassing the transcription start site of PRMT7,
      which we confirmed is functionally a null allele. We show that the patient's
      cells have decreased levels of protein arginine methylation, and that affected
      proteins include the essential histones, H2B and H4. Finally, we demonstrate that
      patient cells have altered Wnt signaling, which may have contributed to the
      skeletal abnormalities. Our findings confirm the recent disease association of
      PRMT7, expand the phenotypic manifestations of this disorder and provide insight
      into the molecular pathogenesis of this new condition.

PMID- 27718517
TI  - Comparative metabolomics analysis of Callosobruchus chinensis larvae under
      hypoxia, hypoxia/hypercapnia and normoxia.
AB  - BACKGROUND: Insect tolerance to low oxygen (hypoxia) and high carbon dioxide
      (hypercapnia) is critical for insect control. On the basis of bioassay,
      metabolism profiles were built to investigate adaptive mechanisms in bean weevil
      under hypoxia (2% O2 ), hypoxia/hypercapnia (2% O2 + 18% CO2 ) and normoxia
      (control, 20% O2 + 80% N2 ) using gas chromatography/time-of-flight mass
      spectrometry (GC/TOF-MS). RESULTS: The growth and development of bean weevils
      were significantly suppressed by the two hypoxia conditions; hypercapnia enhanced
      the mortality, but after 24 days of exposure, the surviving insects emerged as
      adults earlier than those under hypoxia only. Metabolism profiles also showed
      striking differences in metabolites among the treatment and control groups, both
      quantitatively and qualitatively. Pairwise comparisons of the three groups showed
      that 61 metabolites changed significantly, 40 in the hypoxia group and 37 in the
      hypoxia/hypercapnia group relative to the control group, while only 16 were
      shared equally by the hypoxia and hypoxia/hypercapnia groups. Increased
      metabolites were mainly carbohydrates, amino acids and organic acids, while free
      fatty acids were decreased. Furthermore, the changes were strengthened by the
      addition of hypercapnia, but excluding free fatty acids. CONCLUSION: The findings
      show that bean weevil has high tolerance to hypoxia or even hypoxia/hypercapnia
      at biologically achievable levels and provide more direct evidence for stored
      product insect mechanism regulation under hypoxia stress, especially free fatty
      acid regulation by hypercapnia but not by hypoxia. (c) 2016 Society of Chemical
      Industry.

PMID- 27718518
TI  - HAS-BLED Predicts Warfarin Control in Australian Patients treated for Deep Vein
      Thrombosis.
AB  - The HAS-BLED model is widely utilized to assess patients' bleed risk prior to
      anticoagulant therapy including warfarin. Some of the variables assessed in the
      model are also known to influence warfarin control, commonly measured by time in
      therapeutic range (TTR). The aim of the study was to determine whether the HAS
      BLED risk tool is a good predictor of bleed risk and warfarin control in deep
      vein thrombosis (DVT) patients. Retrospective data were collected for DVT
      warfarin care patients at Sullivan Nicolaides Pathology. Data included age,
      medical history and concurrent drug therapy to calculate HAS-BLED scores. INR
      results were used to calculate TTR with the Rosendaal method and mean TTR used
      for analysis and comparison. The eligible 533 patients had a mean TTR of 78.3%.
      Categorization according to HAS-BLED score resulted in 150 patients classified as
      low-risk, 331 as moderate-risk and 52 as high-risk with a haemorrhagic incidence
      per patient of 0.08, 0.53 and 0.54, respectively. Patients in the low-, moderate-
      and high-risk HAS-BLED categories had a mean TTR of 81%, 79% and 65%,
      respectively, with significant differences (p < 0.001) found in TTR between the
      low- and high-risk and moderate- and high-risk categories. In an Australian DVT
      population, the HAS-BLED score accurately predicts decreasing warfarin control
      with increasing risk category, and patients with scores >=3 achieve poor control
      as indicated by a TTR <70%. In addition to predicting bleed risk, the HAS-BLED
      tool may also predict the potential benefit of warfarin treatment and hence
      influence choice of anticoagulant therapy.

PMID- 27718520
TI  - Detecting pyrethroid resistance in predatory mites inhabiting soil and litter: an
      in vitro test.
AB  - BACKGROUND: While resistance against insecticides is widely known in pest
      arthropods, it remains poorly known in non-target arthropods of the same
      agrosystems. This may be of crucial importance in the context of organic pest
      management or integrated pest management. First, stopping of pesticide pressure
      during farm conversion may lead to important rearrangements of non-target
      communities due to fitness cost of resistance in populations of some species.
      Second, resistant biological agents may be useful to farms with low synthetic
      pesticide use. Communities of mesostigmatid mites, encompassing numerous
      predatory species, are supposed to be involved in important ecological processes
      in both crop soils and animal litter/manure. RESULTS: Here we provide a tarsal
      contact method for assessing resistance in different populations from various
      species of mesostigmatid mites. Analyses of data from repeated tests on three
      populations from different mesostigmatid families proved the method to be robust
      and able to generate consistent and reliable mortality percentages according to
      insecticide concentration. CONCLUSION: Our bioassay system allows for both one
      shot estimate of pyrethroid sensitivity in mite populations and estimation of how
      it changes over time, making possible survival analyses and assessment of
      recovery from knockdown. The rating system retained makes it possible to score
      response to insecticides in a consistent and standard way in species from
      different mesostigmatid families. (c) 2016 Society of Chemical Industry.

PMID- 27718519
TI  - Updating the diagnosis, classification and assessment of rosacea: recommendations
      from the global ROSacea COnsensus (ROSCO) panel.
AB  - BACKGROUND: Rosacea is currently diagnosed by consensus-defined primary and
      secondary features and managed by subtype. However, individual features
      (phenotypes) can span multiple subtypes, which has implications for clinical
      practice and research. Adopting a phenotype-led approach may facilitate patient
      centred management. OBJECTIVES: To advance clinical practice by obtaining
      international consensus to establish a phenotype-led rosacea diagnosis and
      classification scheme with global representation. METHODS: Seventeen
      dermatologists and three ophthalmologists used a modified Delphi approach to
      reach consensus on statements pertaining to critical aspects of rosacea
      diagnosis, classification and severity evaluation. All voting was electronic and
      blinded. RESULTS: Consensus was achieved for transitioning to a phenotype-based
      approach to rosacea diagnosis and classification. The following two features were
      independently considered diagnostic for rosacea: (i) persistent, centrofacial
      erythema associated with periodic intensification; and (ii) phymatous changes.
      Flushing, telangiectasia, inflammatory lesions and ocular manifestations were not
      considered to be individually diagnostic. The panel reached agreement on
      dimensions for phenotype severity measures and established the importance of
      assessing the patient burden of rosacea. CONCLUSIONS: The panel recommended an
      approach for diagnosis and classification of rosacea based on disease phenotype.

PMID- 27718521
TI  - Validation of the Simplified Psoriasis Index in Dutch children and adolescents
      with plaque psoriasis.
AB  - BACKGROUND: The Simplified Psoriasis Index (SPI) is a three-domain assessment
      measure for psoriasis, including separate indicators of current severity (SPI-s),
      psychosocial impact (SPI-p), and past history and interventions (SPI-i). There
      are two complementary versions available designed for completion by a health
      professional (proSPI) or by patient self-assessment (saSPI). The validity and
      reliability of the proSPI vs. saSPI have already been demonstrated in adults. To
      date, validated severity measures for paediatric psoriasis do not exist.
      OBJECTIVES: To validate the current severity (SPI-s) and psychosocial impact (SPI
      p) domains of the proSPI and saSPI in children and adolescents with psoriasis.
      METHODS: All patients aged < 18 years with plaque psoriasis visiting the
      dermatology outpatient department of Radboud University Medical Center, the
      Netherlands, between September 2013 and April 2014 were asked to complete Dutch
      versions of the saSPI and the Children's Dermatology Life Quality Index (CDLQI).
      The original English versions of the proSPI and Psoriasis Area and Severity Index
      (PASI) were completed by the physician at the same visit. RESULTS: In total, 113
      patients (median age 12.0 years, range 4-17) were included. There was a close
      correlation between the proSPI-s and PASI (r = 0.87), which was higher than
      between the saSPI-s and PASI (r = 0.69). The correlation between the SPI-p and
      CDLQI was 0.78. The full range of scores was utilized in both proSPI-s and SPI-p,
      although the highest saSPI-s score was 30 (maximum 50). CONCLUSIONS: In
      paediatric psoriasis, the proSPI and saSPI are shown to be valid and usable. The
      SPI-s and SPI-p can be readily introduced into routine clinical practice.

PMID- 27718522
TI  - If prevention is better than cure, is nothing better than prevention?

PMID- 27718523
TI  - Ten-year incidence of contact dermatitis in a prospective cohort of healthcare
      workers in Trieste hospitals (North East of Italy) 2004-2013.

PMID- 27718524
TI  - Antisense locked nucleic acids targeting agrA inhibit quorum sensing and
      pathogenesis of community-associated methicillin-resistant Staphylococcus aureus.
AB  - AIM: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
      is commonly associated with nonnosocomial skin and soft tissue infections due to
      its virulence, which is mainly controlled by the accessory gene regulator (agr)
      quorum sensing (QS) system. In this study (KFF)3 K peptide-conjugated locked
      nucleic acids (PLNAs) targeting agrA mRNA were developed to inhibit agr activity
      and arrest the pathogenicity of CA-MRSA. METHODS AND RESULTS: Two PLNAs were
      designed, and synthesized, after predicting the secondary structure of agrA mRNA.
      The influence on bacterial growth was tested using a growth curve assay. RT-qPCR,
      haemolysis assay, lactate dehydrogenase release assay and chemotaxis assay were
      used to evaluate the effects of the PLNAs on inhibiting agr QS. A mouse skin
      infection model was employed to test the protective effect of the PLNAs in vivo.
      None of the PLNAs were found to be bacteriostatic or bactericidal in vitro.
      However, one PLNA, PLNA34, showed strong ability to suppress expression of agrA
      and the effector molecule RNAIII in USA300 LAC strain. Furthermore, PLNA34
      inhibited the expression of virulence genes that are upregulated by agr,
      including hla, psmalpha, psmbeta and pvl. The haemolytic activity of the
      supernatants from PLNA34-treated bacteria was also dramatically reduced, as well
      as the capacity to lyse and recruit neutrophils. Moreover, PLNA34 showed high
      levels of protection in the CA-MRSA mouse skin infection model. CONCLUSIONS: The
      anti-agrA PLNA34 can effectively inhibit the agr QS and suppress CA-MRSA
      pathogenicity. SIGNIFICANCE AND IMPACT OF THE STUDY: agrA is a promising target
      for the development of antisense oligonucleotides to block agr QS.

PMID- 27718525
TI  - Red cell survival and NO scavenging in sickle cell disease.

PMID- 27718526
TI  - Multimorbidity patterns of oral clinical conditions, social position, and oral
      health-related quality of life in a population-based survey of 12-yr-old
      children.
AB  - The aim of this study was to describe the patterns of multimorbidities of oral
      clinical conditions in children. The association between social position and
      number of oral clinical conditions, and the relationship of social position and
      number of oral clinical conditions with oral health-related quality of life
      [OHRQoL, measured using the Brazilian Child-Oral Impacts on Daily Performance
      (Child-OIDP)] were also investigated. The study analysed data on 7,208 children,
      12 yr of age, from the Brazilian Oral Health Survey (SBBrasil Project). Cluster
      analysis based on the observed/expected (O/E) ratios identified six significant
      clusters of oral clinical conditions: (i) dental caries and missing teeth; (ii)
      dental caries and dental trauma; (iii) dental trauma and gingivitis; (iv) dental
      caries, missing teeth, and dental trauma; (v) dental caries, dental trauma, and
      gingivitis; and (vi) all oral clinical conditions. Ordinal regression showed that
      poor social position was associated with a large number of oral clinical
      conditions. Poisson regression demonstrated that low social position and greater
      number of oral clinical conditions increased the likelihood of poor OHRQoL (Child
      OIDP extent). The four oral clinical conditions clustered into six distinct
      clusters among Brazilian children. Multimorbidity of oral clinical conditions
      predicted poor OHRQoL. Social position was of high relevance to multimorbidity of
      oral clinical conditions and children's OHRQoL.

PMID- 27718527
TI  - A descriptive survey of cancer helplines in the United Kingdom: Who they are, the
      services offered, and the accessibility of those services.
AB  - BACKGROUND: There are more than 1500 UK health helplines in operation, yet we
      have scant knowledge about the resources in place to support the seeking and
      delivering of cancer-related telephone help and support. This research aimed to
      identify and describe cancer and cancer-related helpline service provision: the
      number of helplines available, the variety of services provided, and the
      accessibility of those services. METHOD: This study used online national
      questionnaire survey sent to 95 cancer and cancer-related helplines in the United
      Kingdom. RESULTS: A total of 69 (73%) of 95 surveyed cancer and cancer-related
      helplines completed the survey. Most helplines/organizations were registered
      charities, supported by donations; 73.5% of helplines had national coverage. Most
      helplines served all age-groups, ethnic groups, and men and women. Only 13.4% had
      a number that was free from landlines and most mobile networks, and 56.6% could
      only be contacted during working hours. More than 50% of helplines reported no
      provisions for callers with additional needs, and 55% had no clinical staff
      available to callers. Ongoing support and training for helpline staff was
      available but variable. CONCLUSION: Although cancer helplines in the United
      Kingdom offer reasonably broad coverage across the country, there are still
      potential barriers to accessibility. There are also opportunities to optimize the
      training of staff/volunteers across the sector. There are further prospects for
      helplines to enhance services and sustain appropriate and realistic quality
      standards.

PMID- 27718528
TI  - Childhood body mass index growth trajectories and endometrial cancer risk.
AB  - Previously, we found that excess weight already in childhood has positive
      associations with endometrial cancer; however, associations with changes in body
      mass index (BMI) during childhood are not well understood. Therefore, we examined
      whether growth in childhood BMI is associated with endometrial cancer and its sub
      types. A cohort of 155,505 girls from the Copenhagen School Health Records
      Register with measured weights and heights at the ages of 6-14 years and born
      1930-1989 formed the analytical population. BMI was transformed to age-specific z
      scores. Using linear spline multilevel models, each girl's BMI growth trajectory
      was estimated as the deviance from the average trajectory for three different
      growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health
      registers, 1,020 endometrial cancer cases were identified, and Cox regressions
      were performed. A greater gain in BMI during childhood was positively associated
      with endometrial cancer but no differences between the different growth periods
      were detected in models adjusted for baseline BMI. The hazard ratios for the
      associations with overall growth during childhood per 0.1 z score increase were
      1.15 (95% confidence interval [CI]: 1.07-1.24) for all endometrial cancers, 1.12
      (95% CI: 1.04-1.21) for estrogen-dependent cancers, 1.16 (95% CI: 1.06-1.26) for
      endometrioid adenocarcinomas and 1.46 (95% CI: 1.16-1.84) for non-estrogen
      dependent cancers. Growth in BMI in early life is positively linked to later
      endometrial cancer risk. We did not identify any sensitive childhood growth
      period, which suggests that excess gain in BMI during the entire childhood period
      should be avoided.

PMID- 27718529
TI  - Blepharochalasis: something to cry about.
AB  - Blepharochalasis is a rare disorder of unknown etiology defined by loose,
      atrophic periorbital skin following recurrent episodes of eyelid edema.
      Characteristic histopathology shows complete absence of elastic fibers. The
      current case progressed after multiple episodes of crying, which may be related
      to matrix metalloproteinase dysregulation. This case offers further insights into
      the possible pathogenesis of blepharochalasis, paving the way for more targeted,
      disease-modifying therapies.

PMID- 27718530
TI  - Anti-angiogenic potential of VEGF blocker dendron loaded on to gellan gum
      hydrogels for tissue engineering applications.
AB  - Damage of non-vascularised tissues such as cartilage and cornea can result in
      healing processes accompanied by a non-physiological angiogenesis. Peptidic
      aptamers have recently been reported to block the vascular endothelial growth
      factor (VEGF). However, the therapeutic applications of these aptamers are
      limited due to their short half-life in vivo. In this work, an enhanced stability
      and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was
      pursued through its tethering of molecular scaffolds based on hyperbranched
      peptides, the poly(E-lysine) dendrons, bearing three branching generations. The
      proposed design allowed simultaneous and orderly-spaced exposure of 16 aptamers
      per dendrimer to the surrounding biological microenvironent, as well as a
      relatively hydrophobic core based on di-phenylalanine aiming to promote an
      hydrophobic interaction with the hydrophobic moieties of ionically crosslinked
      methacrylated gellan gum (iGG-MA) hydrogels. The VEGF blocker dendrons were
      entrapped in iGG-MA hydrogels, and their capacity to prevent endothelial cell
      sprouting was assessed qualitatively and quantitatively using 3D in vitro models
      and the in vivo chick chorioallantoic membrane assay. The data demonstrate that
      at nanoscale concentrations, the dendronised structures were able to enhance
      control of the biological actvity of WHLPFKC at the material/tissue interface and
      hence the anti-angiogenic capacity of iGG-MA hydrogels not only preventing blood
      vessel invasion, but also inducing their regression at the tissue/iGG-MA
      interface. The in ovo study confirmed that iGG-MA functionalised with the dendron
      VEGF blockers do inhibit angiogenesis by controlling both size and ramifications
      of blood vessels in the proximity of the implanted gel surface. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27718531
TI  - Living in the city: urban environments shape the evolution of a native annual
      plant.
AB  - Urban environments are warmer, have higher levels of atmospheric CO2 and have
      altered patterns of disturbance and precipitation than nearby rural areas. These
      differences can be important for plant growth and are likely to create distinct
      selective environments. We planted a common garden experiment with seeds
      collected from natural populations of the native annual plant Lepidium
      virginicum, growing in five urban and nearby rural areas in the northern United
      States to determine whether and how urban populations differ from those from
      surrounding rural areas. When grown in a common environment, plants grown from
      seeds collected from urban areas bolted sooner, grew larger, had fewer leaves,
      had an extended time between bolting and flowering, and produced more seeds than
      plants grown from seeds collected from rural areas. Interestingly, the rural
      populations exhibited larger phenotypic differences from one another than urban
      populations. Surprisingly, genomic data revealed that the majority of individuals
      in each of the urban populations were more closely related to individuals from
      other urban populations than they were to geographically proximate rural areas -
      the one exception being urban and rural populations from New York which were
      nearly identical. Taken together, our results suggest that selection in urban
      environments favors different traits than selection in rural environments and
      that these differences can drive adaptation and shape population structure.

PMID- 27718534
TI  - Cargo rigidity affects the sensitivity of dynein ensembles to individual motor
      pausing.
AB  - Cytoplasmic dynein is a minus-end directed microtubule-based motor protein that
      drives intracellular cargo transport in eukaryotic cells. Although many
      intracellular cargos are propelled by small groups of dynein motors, the
      biophysical mechanisms governing ensemble motility remain largely unknown. To
      investigate the emergent motility of motor ensembles, we have designed a
      programmable DNA origami synthetic cargo "chassis" enabling us to control the
      number of dynein motors in the ensemble and vary the rigidity of the cargo
      chassis itself. Using total internal reflection fluorescence microscopy, we have
      observed dynein ensembles transporting these cargo chassis along microtubules in
      vitro. We find that ensemble motility depends on cargo rigidity: as the number of
      motors increases, ensembles transporting flexible cargos move comparatively
      faster than a single motor, whereas ensembles transporting rigid cargos move
      slower than a single motor. To explain this, we show that ensembles connected
      through flexible cargos are less sensitive to the pauses of individual motors
      within the ensemble. We conclude that cargo rigidity plays an important role in
      communicating and coordinating the states of motors, and consequently in the
      subsequent mechanisms of collective motility. The insensitivity of ensemble
      driven cargos to the pausing of individual motors may contribute to the
      robustness and versatility of intracellular cargo transport. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27718532
TI  - Identification of miRSNPs associated with the risk of multiple myeloma.
AB  - Multiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the
      bone marrow, associated with the production of a monoclonal immunoglobulin (M
      protein) which can be detected in the blood and/or urine. Multiple lines of
      evidence suggest that genetic factors are involved in MM pathogenesis, and
      several studies have identified single nucleotide polymorphisms (SNPs) associated
      with the susceptibility to the disease. SNPs within miRNA-binding sites in target
      genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus
      deregulating protein expression. MiRSNPs are known to be associated with risk of
      various types of cancer, but they have never been investigated in MM. We
      performed an in silico genome-wide search for miRSNPs predicted to alter binding
      of miRNAs to their target sequences. We selected 12 miRSNPs and tested their
      association with MM risk. Our study population consisted of 1,832 controls and
      2,894 MM cases recruited from seven European countries and Israel in the context
      of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this
      population two SNPs showed an association with p < 0.05: rs286595 (located in
      gene MRLP22) and rs14191881 (located in gene TCF19). Results from IMMEnSE were
      meta-analyzed with data from a previously published genome-wide association study
      (GWAS). The SNPs rs13409 (located in the 3'UTR of the POU5F1 gene), rs1419881
      (TCF19), rs1049633, rs1049623 (both in DDR1) showed significant associations with
      MM risk. In conclusion, we sought to identify genetic polymorphisms associated
      with MM risk starting from genome-wide prediction of miRSNPs. For some mirSNPs,
      we have shown promising associations with MM risk.

PMID- 27718533
TI  - Improving anxiety regulation in patients with breast cancer at the beginning of
      the survivorship period: a randomized clinical trial comparing the benefits of
      single-component and multiple-component group interventions.
AB  - OBJECTIVE: To compare in a multicenter randomized controlled trial the benefits
      in terms of anxiety regulation of a 15-session single-component group
      intervention (SGI) based on support with those of a 15-session multiple-component
      structured manualized group intervention (MGI) combining support with cognitive
      behavioral and hypnosis components. METHODS: Patients with nonmetastatic breast
      cancer were randomly assigned at the beginning of the survivorship period to the
      SGI (n = 83) or MGI (n = 87). Anxiety regulation was assessed, before and after
      group interventions, through an anxiety regulation task designed to assess their
      ability to regulate anxiety psychologically (anxiety levels) and physiologically
      (heart rates). Questionnaires were used to assess psychological distress,
      everyday anxiety regulation, and fear of recurrence. Group allocation was
      computer generated and concealed till baseline completion. RESULTS: Compared with
      patients in the SGI group (n = 77), patients attending the MGI group (n = 82)
      showed significantly reduced anxiety after a self-relaxation exercise (P = .006)
      and after exposure to anxiety triggers (P = .013) and reduced heart rates at
      different time points throughout the task (P = .001 to P = .047). The MGI
      participants also reported better everyday anxiety regulation (P = .005), greater
      use of fear of recurrence-related coping strategies (P = .022), and greater
      reduction in fear of recurrence-related psychological distress (P = .017)
      compared with the SGI group. CONCLUSIONS: This study shows that an MGI combining
      support with cognitive-behavioral techniques and hypnosis is more effective than
      an SGI based only on support in improving anxiety regulation in patients with
      breast cancer.

PMID- 27718535
TI  - The rhythm of the executive gate of speech: subthalamic low-frequency
      oscillations increase during verbal generation.
AB  - We investigated neurophysiological mechanisms of subthalamic nucleus involvement
      in verbal fluency through a verbal generation task. The subthalamic nucleus is
      thought to act as a behavioural go/no-go instance by means of oscillatory
      communication in the theta band with the prefrontal cortex. Because subthalamic
      alpha-theta frequency stimulation has been shown to exert beneficial effects on
      verbal fluency in Parkinson's disease, we hypothesized that an alpha-theta
      oscillatory network involving the subthalamic nucleus underlies verbal generation
      task performance as a gating instance for speech execution. Postoperative
      subthalamic local field potential recordings were performed during a verbal
      generation compared to a control task. Time-frequency analysis revealed a
      significant alpha-theta power increase and enhanced alpha-theta coherence between
      the subthalamic nucleus and the frontal surface EEG during the verbal generation
      task. Beta and gamma oscillations were not significantly modulated by the task.
      Power increase significantly correlated with verbal generation performance. Our
      results provide experimental evidence for local alpha-theta oscillatory activity
      in the subthalamic nucleus and coherence to frontal associative areas as a
      neurophysiological mechanism underlying a verbal generation task. Thus, verbal
      fluency improvement during subthalamic alpha-theta stimulation in Parkinson's
      disease is likely due to an enhancement of alpha-theta oscillatory network
      activity. Alpha-theta oscillations can be interpreted as the rhythmic gating
      signature in a speech executing subthalamic-prefrontal network.

PMID- 27718536
TI  - Encoding of global visual motion in the nidopallium caudolaterale of behaving
      crows.
AB  - Songbirds possess acute vision. How higher brain centres represent basic and
      parameterised visual stimuli to process sensory signals according to their
      behavioural importance has not been studied in a systematic way. We therefore
      examined how carrion crows (Corvus corone) and their nidopallial visual neurons
      process global visual motion information in dynamic random-dot displays during a
      delayed match-to-sample (DMS) task. The behavioural data show that moderately
      fast motion speeds (16 degrees  of visual angle/s) result in superior direction
      discrimination performance. To characterise how neurons encode and maintain task
      relevant visual motion information, we recorded the single-unit activity in the
      telencephalic association area 'nidopallium caudolaterale' (NCL) of behaving
      crows. The NCL is considered to be the avian analogue of the mammalian prefrontal
      cortex. Almost a third (28%) of randomly selected NCL neurons responded
      selectively to the motion direction of the sample stimulus, mostly to downward
      motions. Only few NCL neurons (7.5%) responded consistently to specific motion
      directions during the delay period. In error trials, when the crows chose the
      wrong motion direction, the encoding of motion direction was significantly
      reduced. This indicates that sensory representations of NCL neurons are relevant
      to the birds' behaviour. These data suggest that the corvid NCL, even though
      operating at the apex of the telencephalic processing hierarchy, constitutes a
      telencephalic site for global motion integration.

PMID- 27718538
TI  - Pregnancy as a driver for melanoma.
AB  - Whether or not pregnancy favours the occurrence and growth of melanoma is a
      source of controversy in the literature. Several case reports have shown dramatic
      courses of diseases in pregnancy. We present a case of a 36-year-old woman with
      multiple naevi with one melanoma detected in 2009 in the first trimester and a
      second primary melanoma in 2010 in the third trimester of her pregnancy. Both
      lesions have been present for at least 5 years and have been interpreted as
      dysplastic naevi. Because of their growth during pregnancy they were removed. No
      metastatic disease has been found between 2010 and early 2017. This case shows
      the difficulty of detecting melanomas in pregnancy, particularly when they mimic
      dysplastic naevi in women with multiple naevi, who are at higher risk. Therefore,
      we suggest that pregnant women with numerous naevi should be precautious of any
      changes of their naevi in size, shape and colour. Every suspicious lesion should
      be either excised or documented/monitored carefully, for example with sequential
      digital dermoscopy imaging.

PMID- 27718537
TI  - Adaptive dynamics of cuticular hydrocarbons in Drosophila.
AB  - Cuticular hydrocarbons (CHCs) are hydrophobic compounds deposited on the
      arthropod cuticle that are of functional significance with respect to stress
      tolerance, social interactions and mating dynamics. We characterized CHC profiles
      in natural populations of Drosophila melanogaster at five levels: across a
      latitudinal transect in the eastern United States, as a function of developmental
      temperature during culture, across seasonal time in replicate years, and as a
      function of rapid evolution in experimental mesocosms in the field. Furthermore,
      we also characterized spatial and temporal changes in allele frequencies for SNPs
      in genes that are associated with the production and chemical profile of CHCs.
      Our data demonstrate a striking degree of parallelism for clinal and seasonal
      variation in CHCs in this taxon; CHC profiles also demonstrate significant
      plasticity in response to rearing temperature, and the observed patterns of
      plasticity parallel the spatiotemporal patterns observed in nature. We find that
      these congruent shifts in CHC profiles across time and space are also mirrored by
      predictable shifts in allele frequencies at SNPs associated with CHC chain
      length. Finally, we observed rapid and predictable evolution of CHC profiles in
      experimental mesocosms in the field. Together, these data strongly suggest that
      CHC profiles respond rapidly and adaptively to environmental parameters that
      covary with latitude and season, and that this response reflects the process of
      local adaptation in natural populations of D. melanogaster.

PMID- 27718539
TI  - Effective cancer targeting and imaging using macrophage membrane-camouflaged
      upconversion nanoparticles.
AB  - Upconversion nanoparticles (UCNPs), with fascinating optical and chemical
      features, are a promising new generation of fluorescent probes. Although UCNPs
      have been widely used in diagnosis and therapy, there is an unmet need for a
      simple and effective surface engineering method that can produce cancer-targeting
      UCNPs. Here, we show that by coating particles with macrophage membranes, it
      becomes possible to utilize the adhesion between macrophages and cancer cells for
      effective cancer targeting. Natural macrophage membranes along with their
      associated membrane proteins were reconstructed into vesicles and then coated
      onto synthetic UCNPs. The resulting macrophage membrane-camouflaged particles (MM
      UCNPs) exhibited effective cancer targeting capability inherited from the source
      cells and were further used for enhanced in vivo cancer imaging. Finally, the
      blood biochemistry, hematology testing and histology analysis results suggested a
      good in vivo biocompatibility of MM-UCNPs. The combination of synthetic
      nanoparticles with biomimetic cell membranes embodies a novel design strategy
      toward developing biocompatible nanoprobes for potential clinical applications.
      (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 521-530, 2017.

PMID- 27718542
TI  - Dry-Processed, Binder-Free Holey Graphene Electrodes for Supercapacitors with
      Ultrahigh Areal Loadings.
AB  - For commercial applications, the need for smaller footprint energy storage
      devices requires more energy to be stored per unit area. Carbon nanomaterials,
      especially graphene, have been studied as supercapacitor electrodes and can
      achieve high gravimetric capacities affording high gravimetric energy densities.
      However, most nanocarbon-based electrodes exhibit a significant decrease in their
      areal capacitances when scaled to the high mass loadings typically used in
      commercially available cells (~10 mg/cm2). One of the reasons for this behavior
      is that the additional surface area in thick electrodes is not readily accessible
      by electrolyte ions due to the large tortuosity. Furthermore, the fabrication of
      such electrodes often involves complicated processes that limit the potential for
      mass production. Here, holey graphene electrodes for supercapacitors that are
      scalable in both production and areal capacitance are presented. The lateral
      surface porosity on the graphene sheets was created using a facile single-step
      air oxidation method, and the resultant holey graphene was compacted under
      ambient conditions into mechanically robust monolithic shapes that can be
      directly used as binder-free electrodes. In comparison, pristine graphene discs
      under similar binder-free compression molding conditions were extremely brittle
      and thus not deemed useful for electrode applications. The coin cell
      supercapacitors, based on these holey graphene electrodes exhibited small
      variations in gravimetric capacitance over a wide range of areal mass loadings
      (~1-30 mg/cm2) at current densities as high as 30 mA/cm2, resulting in the near
      linear increase of the areal capacitance (F/cm2) with the mass loading. The
      prospects of the presented method for facile binder-free ultrathick graphene
      electrode fabrication are discussed.

PMID- 27718541
TI  - Trafficking of adeno-associated virus vectors across a model of the blood-brain
      barrier; a comparative study of transcytosis and transduction using primary human
      brain endothelial cells.
AB  - Developing therapies for central nervous system (CNS) diseases is exceedingly
      difficult because of the blood-brain barrier (BBB). Notably, emerging
      technologies may provide promising new options for the treatment of CNS
      disorders. Adeno-associated virus serotype 9 (AAV9) has been shown to transduce
      cells in the CNS following intravascular administration in rodents, cats, pigs,
      and non-human primates. These results suggest that AAV9 is capable of crossing
      the BBB. However, mechanisms that govern AAV9 transendothelial trafficking at the
      BBB remain unknown. Furthermore, possibilities that AAV9 may transduce brain
      endothelial cells or affect BBB integrity still require investigation. Using
      primary human brain microvascular endothelial cells as a model of the human BBB,
      we performed transduction and transendothelial trafficking assays comparing AAV9
      to AAV2, a serotype that does not cross the BBB or transduce endothelial cells
      effectively in vivo. Results of our in vitro studies indicate that AAV9
      penetrates brain microvascular endothelial cells barriers more effectively than
      AAV2, but has reduced transduction efficiency. In addition, our data suggest that
      (i) AAV9 penetrates endothelial barriers through an active, cell-mediated
      process, and (ii) AAV9 fails to disrupt indicators of BBB integrity such as
      transendothelial electrical resistance, tight junction protein
      expression/localization, and inflammatory activation status. Overall, this report
      shows how human brain endothelial cells configured in BBB models can be utilized
      for evaluating transendothelial movement and transduction kinetics of various AAV
      capsids. Importantly, the use of a human in vitro BBB model can provide import
      insight into the possible effects that candidate AVV gene therapy vectors may
      have on the status of BBB integrity. Read the Editorial Highlight for this
      article on page 192.

PMID- 27718543
TI  - A Robust Versatile Hybrid Electrocatalyst for the Oxygen Reduction Reaction.
AB  - Identifying non-precious-metal catalysts with desirable overall performance for
      oxygen reduction reaction (ORR) in either acidic or basic media is still a
      bottleneck. Here, a hybrid material is reported, in which tungsten carbide (WC)
      and ferberite (FeWO4) are attached to the Fe and N dual-doped ordered mesoporous
      carbon (WC-FeWO4@FeN-OMC) as a superior performance catalyst for the ORR in
      either acidic or basic media. In comparison with the frequently used Pt/C ORR
      catalyst (20 wt. %), our hybrid materials exhibit comparable electrocatalytic
      activity mainly via a 4e ORR process, better stability, and total tolerance to
      methanol in either acidic or basic media. These advantages, especially the
      outstanding stability in acidic media, render the WC-FeWO4@FeN-OMC as a promising
      potential non-precious-metal ORR catalyst in practical fuel cell applications.

PMID- 27718540
TI  - Germline BAP1 alterations in familial uveal melanoma.
AB  - Uveal melanoma (UM) is the most commonly diagnosed primary intraocular tumor in
      adults. Familial UM (FUM), defined as two or more family members diagnosed with
      UM, is rare and estimated at less than 1% of all UM. Currently, BAP1 is the only
      gene known to contribute significant risk for UM. In this study we aimed to
      estimate the frequency of BAP1 mutation in FUM and to characterize the family and
      personal histories of other cancers in these families. We identified 32 families
      with FUM, including seven families previously reported by our group. BAP1
      mutation testing was carried out by direct sequencing of the coding exons and the
      adjacent untranslated regions of the gene. Germline deletion and duplication
      analysis of BAP1 was assessed by multiplex ligation-dependent probe amplification
      (MLPA). Germline BAP1 mutations were found in 6/32 (19%) families. No deletions
      or duplications were identified in any of the 24 samples tested by MLPA. Combined
      with published studies, the frequency of BAP1 mutations was 14/64 (22%) in FUM.
      FUM families without BAP1 mutations have distinct family histories with high
      rates of prostate cancer in first- and second-degree relatives. It is likely that
      additional genes conferring risk for FUM exist. It is important to understand key
      shared features of FUM to focus future research on identifying these additional
      tumor predisposition syndromes. Though BAP1 should be tested first in these
      families, FUM families without BAP1 mutation should be explored for additional
      predisposition genes. (c) 2016 Wiley Periodicals, Inc.

PMID- 27718544
TI  - Salinity Gradients for Sustainable Energy: Primer, Progress, and Prospects.
AB  - Combining two solutions of different composition releases the Gibbs free energy
      of mixing. By using engineered processes to control the mixing, chemical energy
      stored in salinity gradients can be harnessed for useful work. In this critical
      review, we present an overview of the current progress in salinity gradient power
      generation, discuss the prospects and challenges of the foremost technologies -
      pressure retarded osmosis (PRO), reverse electrodialysis (RED), and capacitive
      mixing (CapMix) and provide perspectives on the outlook of salinity gradient
      power generation. Momentous strides have been made in technical development of
      salinity gradient technologies and field demonstrations with natural and
      anthropogenic salinity gradients (for example, seawater-river water and
      desalination brine-wastewater, respectively), but fouling persists to be a
      pivotal operational challenge that can significantly ebb away cost
      competitiveness. Natural hypersaline sources (e.g., hypersaline lakes and salt
      domes) can achieve greater concentration difference and, thus, offer
      opportunities to overcome some of the limitations inherent to seawater-river
      water. Technological advances needed to fully exploit the larger salinity
      gradients are identified. While seawater desalination brine is a seemingly
      attractive high salinity anthropogenic stream that is otherwise wasted, actual
      feasibility hinges on the appropriate pairing with a suitable low salinity
      stream. Engineered solutions are foulant-free and can be thermally regenerative
      for application in low-temperature heat utilization. Alternatively, PRO, RED, and
      CapMix can be coupled with their analog separation process (reverse osmosis,
      electrodialysis, and capacitive deionization, respectively) in salinity gradient
      flow batteries for energy storage in chemical potential of the engineered
      solutions. Rigorous techno-economic assessments can more clearly identify the
      prospects of low-grade heat conversion and large-scale energy storage. While
      research attention is squarely focused on efficiency and power improvements,
      efforts to mitigate fouling and lower membrane and electrode cost will be equally
      important to reduce levelized cost of salinity gradient energy production and,
      thus, boost PRO, RED, and CapMix power generation to be competitive with other
      renewable technologies. Cognizance of the recent key developments and technical
      progress on the different technological fronts can help steer the strategic
      advancement of salinity gradient as a sustainable energy source.

PMID- 27718546
TI  - Homologous Compounds ZnnIn2O3+n (n = 4, 5, and 7) Containing Laminated Functional
      Groups as Efficient Photocatalysts for Hydrogen Production.
AB  - Strong visible light absorption and high charge mobility are desirable properties
      for an efficient photocatalyst, yet they are hard to be realized simultaneously
      in a single semiconductor compound. In this work, we demonstrate that these
      properties coexist in homologous compounds ZnnIn2O3+n (n = 4, 5, and 7) with a
      peculiar layered structure that combines optical active segment and electrical
      conductive segment together. Their enhanced visible light absorption originates
      from tetrahedrally or trigonal-bipyramidally coordinated In atoms in Zn(In)O4(5)
      layers which enable p-d hybridization between In 4d and O 2p orbitals so that
      valence band minimum (VBM) is uplifted with a reduced band gap. Theoretical
      calculations reveal their anisotropic features in charge transport and
      functionality of different constituent segments, i.e., Zn(In)O4(5) layers and
      InO6 layers as being for charge generation and charge collection, respectively.
      Efficient photocatalytic hydrogen evolution was observed in these compounds under
      full range (lambda >= 250 nm) and visible light irradiation (lambda >= 420 nm).
      High apparent quantum efficiency ~2.79% was achieved for Zn4In2O7 under full
      range irradiation, which is almost 5-fold higher than their parent oxides ZnO and
      In2O3. Such superior photocatalytic activities of these homologous compounds can
      be understood as layer-by-layer packing of charge generation/collection
      functional groups that ensures efficient photocatalytic reactions.

PMID- 27718545
TI  - Passage Variation of PC12 Cells Results in Inconsistent Susceptibility to
      Externally Induced Apoptosis.
AB  - The PC12 cell line is a widely used in vitro model for screening the
      neuroprotective activity of small molecule libraries. External insult due to
      serum deprivation or addition of etoposide induces cell death by apoptosis. While
      this screening method is commonly used in early stage drug discovery no protocol
      accounting for cell passage number effect on neuroprotective activity has been
      disclosed. We herein report that passage variation results in false
      positive/false-negative identification of neuroprotective compounds;
      undifferentiated PC12 cells with high passage number are less sensitive to injury
      induced by serum-deprivation or etoposide treatment. In contrast, NGF
      differentiated PC12 cells of later passage number are more sensitive to injury
      induced by etoposide than lower passage number but only after 72 h. Passage
      number also affects the adherence phenotype of the PC12 cells, complicating
      screening assays. We report an optimized protocol for screening the
      neuroprotective activity of small molecules in PC12 cells, which accounts for
      passage number variations.

PMID- 27718547
TI  - Photopatterned Single-Walled Carbon Nanotube Films Utilizing the
      Adsorption/Desorption Processes of Photofunctional Dispersants.
AB  - We describe the application of photodetachable and recyclable dispersants for
      single-walled carbon nanotubes (SWNTs) in the fabrication of photopatterned SWNT
      thin films. Because adsorption and desorption of the dispersants on the SWNT
      surfaces affect not only their dispersibility in water but also their solubility,
      SWNT photopatterns were obtained on glass substrates in only three steps, i.e.,
      casting the SWNT/dispersant solution, UV-light exposure of the casted
      SWNT/dispersant films through a photomask, and subsequent rinsing with neutral
      water. This patterning procedure is simple and scalable and will enable us to
      prepare microfabricated SWNT thin films.

PMID- 27718548
TI  - Isomeric Sc2O@C78 Related by a Single-Step Stone-Wales Transformation: Key Links
      in an Unprecedented Fullerene Formation Pathway.
AB  - It has been proposed that the fullerene formation mechanism involves either a top
      down or bottom-up pathway. Despite different starting points, both mechanisms
      approve that particular fullerenes or metallofullerenes are formed through a
      consecutive stepwise process involving Stone-Wales transformations (SWTs) and C2
      losses or additions. However, the formation pathway has seldomly been defined at
      the atomic level due to the missing-link fullerenes. Herein, we present the
      isolation and crystallographic characterization of two isomeric clusterfullerenes
      Sc2O@C2v(3)-C78 and Sc2O@D3h(5)-C78, which are closely related via a single-step
      Stone-Wales (SW) transformation. More importantly, these novel Sc2O@C78 isomers
      represent the key links in a well-defined formation pathway for the majority of
      solvent-extractable clusterfullerenes Sc2O@C2n (n = 38-41), providing molecular
      structural evidence for the less confirmed fullerene formation mechanism.
      Furthermore, DFT calculations reveal a SWT with a notably low activation barrier
      for these Sc2O@C78 isomers, which may rationalize the established fullerene
      formation pathway. Additional characterizations demonstrate that these Sc2O@C78
      isomers feature different energy bandgaps and electrochemical behaviors,
      indicating the impact of SW defects on the energetic and electrochemical
      characteristics of metallofullerenes.

PMID- 27718549
TI  - Role of Nitrogen Doped Graphene for Improved High Capacity Potassium Ion Battery
      Anodes.
AB  - Potassium is an earth abundant alternative to lithium for rechargeable batteries,
      but a critical limitation in potassium ion battery anodes is the low capacity of
      KC8 graphite intercalation compounds in comparison to conventional LiC6. Here we
      demonstrate that nitrogen doping of few-layered graphene can increase the storage
      capacity of potassium from a theoretical maximum of 278 mAh/g in graphite to over
      350 mAh/g, competitive with anode capacity in commercial lithium-ion batteries
      and the highest reported anode capacity so far for potassium ion batteries.
      Control studies distinguish the importance of nitrogen dopant sites as opposed to
      sp3 carbon defect sites to achieve the improved performance, which also enables >
      6X increase in rate performance of doped versus undoped materials. Finally, in
      situ Raman spectroscopy studies elucidate the staging sequence for doped and
      undoped materials and demonstrate the mechanism of the observed capacity
      enhancement to be correlated with distributed storage at local nitrogen sites in
      a staged KC8 compound. This study demonstrates a pathway to overcome the
      limitations of graphitic carbons for anodes in potassium ion batteries by
      atomically precise engineering of nanomaterials.

PMID- 27718552
TI  - Elucidating the Surface Reactions of an Amorphous Si Thin Film as a Model
      Electrode for Li-Ion Batteries.
AB  - We investigated during the first lithiation/delithiation process the
      electrochemical reaction mechanisms at the surface of 30 nm n-doped amorphous
      silicon (a-Si) thin film used as a negative model electrode for Li-ion batteries.
      Usage of thin film allowed us to accurately discern the different reaction
      mechanisms occurring at the surface by avoiding interference from carbon and
      binder components. The potential dependency of the evolution of the solid
      electrolyte interphase (SEI) and the reactions on the a-Si and on the copper
      current collector were elucidated by coupling galvanostatic cycling with
      postmortem X-ray photoemission spectroscopy and scanning electron microscopy
      analyses. Our approach revealed the clear reversibility of
      lithiation/delithiation in the a-Si and native SiO2 layers; such a reaction for
      SiO2 has not been previously detected and was considered to be an irreversible
      process. Quantitative and qualitative analyses of the potential-dependent surface
      evolution revealed the decomposition products of both the salt (LiPF6) and
      solvent (dimethyl carbonate/ethylene carbonate), giving insight into the complex
      SEI formation mechanism on the a-Si film but also underlining the strong
      influence of "inert" materials such as the role of the current collector in the
      irreversible charge loss. A model mechanism describing the evolutionary
      complexity of the a-Si surface during the first galvanostatic cycle is proposed
      and discussed.

PMID- 27718553
TI  - A New Class of Atomically Precise, Hydride-Rich Silver Nanoclusters Co-Protected
      by Phosphines.
AB  - Thiols and phosphines are the most widely used organic ligands to attain
      atomically precise metal nanoclusters (NCs). Here, we used simple hydrides (e.g.,
      H-) as ligands along with phos-phines, such as triphenylphosphine (TPP), 1,2
      bis(diphenylphosphino)ethane [DPPE], and tris(4-fluorophenyl)phosphine [TFPP] to
      design and synthesize a new class of hydride-rich silver NCs. This class includes
      [Ag18H16(TPP)10]2+, [Ag25H22(DPPE)8]3+, and [Ag26H22(TFPP)13]2+. Our work reveals
      a new family of atomi-cally precise NCs protected by H- ligands and labile phos
      phines, with potentially more accessible active metal sites for functionalization
      and provides a new set of stable NC sizes with simpler ligand-metal bonding for
      researchers to explore both experimentally and computationally.

PMID- 27718550
TI  - L30A Mutation of Phospholemman Mimics Effects of Cardiac Glycosides in Isolated
      Cardiomyocytes.
AB  - To determine if mutations introduced into phospholemman (PLM) could increase the
      level of PLM-Na,K-ATPase (NKA) binding, we performed scanning mutagenesis of the
      transmembrane domain of PLM and measured Forster resonance energy transfer (FRET)
      between each mutant and NKA. We observed an increased level of binding to NKA for
      several PLM mutants compared to that of the wild type (WT), including L27A, L30A,
      and I32A. In isolated cardiomyocytes, overexpression of WT PLM increased the
      amplitude of the Ca2+ transient compared to the GFP control. The Ca2+ transient
      amplitude was further increased by L30A PLM overexpression. The L30A mutation
      also delayed Ca2+ extrusion and increased the duration of cardiomyocyte
      contraction. This mimics aspects of the effect of cardiac glycosides, which are
      known to increase contractility through inhibition of NKA. No significant
      differences between WT and L30A PLM-expressing myocytes were observed after
      treatment with isoproterenol, suggesting that the superinhibitory effects of L30A
      are reversible with beta-adrenergic stimulation. We also observed a decrease in
      the extent of PLM tetramerization with L30A compared to WT using FRET, suggesting
      that L30 is an important residue for mediating PLM-PLM binding. Molecular
      dynamics simulations revealed that the potential energy of the L30A tetramer is
      greater than that of the WT, and that the transmembrane alpha helix is distorted
      by the mutation. The results identify PLM residue L30 as an important determinant
      of PLM tetramerization and of functional inhibition of NKA by PLM.

PMID- 27718551
TI  - Paired Design of dCas9 as a Systematic Platform for the Detection of Featured
      Nucleic Acid Sequences in Pathogenic Strains.
AB  - We developed an in vitro DNA detection system using a pair of dCas9 proteins
      linked to split halves of luciferase. Luminescence was induced upon
      colocalization of the reporter pair to a ~44 bp target sequence defined by
      sgRNAs. We used the system to detect Mycobacterium tuberculosis DNA with high
      specificity and sensitivity. The reprogrammability of dCas9 was further leveraged
      in an array design that accesses sequence information across the entire genome.

PMID- 27718554
TI  - Reliable Memristive-Switching Memory Devices Enabled by Densely-Packed Silver
      Nanocone Arrays as Electric-Field Concentrators.
AB  - Memristor devices based on electrochemical metallization operate through
      electrochemical formation/dissolution of nanoscale metallic filaments, and they
      are considered a promising future nonvolatile memory because of their outstanding
      characteristics over conventional charge-based memories. However, nanoscale
      conductive paths or filaments precipitated from the redox process of metallic
      elements are randomly formed inside oxides resulting in unexpected and stochastic
      memristive switching parameters including the operating voltage and the
      resistance state. Here, we present the guided formation of conductive filaments
      in Ag nanocone/SiO2 nanomesh/Pt memristors fabricated by high-resolution
      nanotransfer printing. Consequently, the uniformity of the memristive switching
      behavior is significantly improved by the existence of electric field
      concentrator arrays consisting of Ag nanocones embedded in SiO2 nanomesh
      structures. This selective and controlled filament growth was experimentally
      supported by analyzing simultaneously the surface morphology and current-mapping
      results using conductive atomic-force microscopy. Moreover, stable multi-level
      switching operations with four discrete conduction states were achieved by the
      nanopatterned memristor device demonstrating its potential in high-density
      nanoscale memory devices.

PMID- 27718555
TI  - Modulating Drug Release Rate from Partially Silica-Coated Bicellar Nanodisc by
      Incorporating PEGylated Phospholipid.
AB  - This article reports an effective method to regulate hydrophobic drug release
      rate from partially silica-coated bicellar nanodisc generated from proamphiphilic
      organoalkoxysilane and dihexanoylphosphatidylcholine by introducing different
      molar percentages of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000
      (DSPE-PEG2000) into planar bilayers of hybrid bicelles. It was found that the
      drug release rate increased with increasing the molar percentages of DSPE
      PEG2000, and 57.38%, 69.21%, 78.69%, 81.64%, and 82.23% of hydrophobic
      doxorubicin was released within 120 h from the nanodics incorporating with 0%,
      2.5%, 5%, 10%, and 20% DSPE-PEG2000, respectively. Compared with the non
      PEGylated nanodisc and free doxorubicin, the PEGylated nanodiscs showed good
      biocompatibility, high cellular uptake, and adhesion, as well as high local drug
      accumulation. In addition, both in vitro and in vivo results demonstrated
      significantly improved antitumor efficacy of the PEGylated nanodisc than its
      control groups. Thus, the PEGylated nanodisc with partial silica coating offers a
      facile and efficient strategy of drug delivery for chemotherapy with improved
      patient acceptance and compliance.

PMID- 27718556
TI  - In Situ Natural Abundance 17O and 25Mg NMR Investigation of Aqueous Mg(OH)2
      Dissolution in the Presence of Supercritical CO2.
AB  - We report an in situ high-pressure NMR capability that permits natural abundance
      17O and 25Mg NMR characterization of dissolved species in aqueous solution and in
      the presence of supercritical CO2 fluid (scCO2). The dissolution of Mg(OH)2
      (brucite) in a multiphase water/scCO2 fluid at 90 atm pressure and 50  degrees C
      was studied in situ, with relevance to geological carbon sequestration. 17O NMR
      spectra allowed identification and distinction of various fluid species including
      dissolved CO2 in the H2O-rich phase, scCO2, aqueous H2O, and HCO3-. The widely
      separated spectral peaks for various species can all be observed both dynamically
      and quantitatively at concentrations as low as 20 mM. Measurement of the
      concentrations of these individual species also allows an in situ estimate of the
      hydrogen ion concentration, or pCH+ values, of the reacting solutions. The
      concentration of Mg2+ can be observed by natural abundance 25Mg NMR at a
      concentration as low as 10 mM. Quantum chemistry calculations of the NMR chemical
      shifts on cluster models aided in the interpretation of the experimental results.
      Evidence for the formation of polymeric Mg2+ clusters at high concentrations in
      the H2O-rich phase, a possible critical step needed for magnesium carbonate
      formation, was found.

PMID- 27718557
TI  - Enhanced Light Emission from Monolayer Semiconductors by Forming Heterostructures
      with ZnO Thin Films.
AB  - Monolayer transition-metal dichalcogenides (1L-TMDs) are atomically thin direct
      band gap semiconductors, from which the emission of light is determined by
      optical transitions of exciton complexes such as neutral excitons and trions.
      While the quantum yields of 1L-TMDs are quite low, the ability to control the
      populations of exciton complexes in 1L-TMDs through various doping processes is
      an interesting advantage, and provides ample possibilities for engineering the
      optical properties of these semiconductor monolayers. Here we demonstrate a
      simple method of controlling the populations of excitons and trions to enhance
      the light emission of 1L-TMDs by having them form heterostructures with ZnO thin
      films (TFs). 1Ls of MoS2 or MoSe2 showed up to 17-fold increases in
      photoluminescence (PL) when they were placed on ~50 nm thick ZnO TFs. This
      enhancement of the PL was due to charge exchanges occurring through the 1L
      TMD/ZnO interface. The PL enhancements and changes in the PL spectra of the 1L
      TMDs were greater when the 1L-TMD/ZnO heterostructures were subjected to 355 nm
      wavelength laser excitation than when they were excited with a 514 nm wavelength
      laser, which we attributed to the onset of energy transfer by photoexcited
      excitons and/or the additional p-doping by photoexcited holes in ZnO. The p
      doping phenomenon and the enhanced light emission of 1L-TMD/ZnO heterostructures
      were unambiguously visualized in spatially resolved PL and Raman spectral maps.
      Our approach using the 1L-TMD/ZnO TF heterostructure suggests that a rich variety
      of options for engineering the optical properties of 1L-TMDs may be made
      available by carrying out simple and intuitive manipulations of exciton
      complexes, and these endeavors may yield practical applications for 1L-TMDs in
      nanophotonic devices.

PMID- 27718559
TI  - Facilitated Bioaccumulation of Perfluorooctanesulfonate in Common Carp (Cyprinus
      carpio) by Graphene Oxide and Remission Mechanism of Fulvic Acid.
AB  - As one of the most popular carbon-based nanomaterials, graphene oxide (GO) has
      the potential to be released in aquatic environment and interact with some
      coexistent organic pollutants, such as perfluorooctanesulfonate (PFOS), which is
      an emerging persistent organic pollutant. In this study, the adsorption of PFOS
      on GO in the presence of fulvic acid (FA), the impacts of GO and FA on PFOS
      toxicokinetics in carp (Cyprinus carpio), and in vitro digestion behaviors were
      examined. The results indicated that PFOS could be strongly adsorbed on GO with a
      Freundlich affinity coefficient KF of 580 +/- 205 (mg/g)/(mg/L)n, while the
      adsorption was suppressed by FA due to competitive adsorption. GO significantly
      enhanced the bioaccumulation of PFOS in blood, kidney, liver, gill, intestine,
      and muscle of carp, and the corresponding bioaccumulation factor (BAF) was in the
      range of 2026-53513 L/kg. The enhancement was greatest for liver and intestine,
      which was 10.3 and 9.33 times of that without GO, respectively. In vivo
      toxicokinetic and in vitro digestion-absorption experiments indicated that GO
      could carry PFOS to penetrate the intestine cells. There herein, PFOS absorption,
      especially via intestine, and the uptake rate coefficient (ku) were greatly
      enhanced, leading to distinctly promoted bioaccumulation of PFOS in fish.
      However, FA could facilitate the flocculation of GO in the intestine and also
      accelerate excretion of GO-PFOS complex. Thus, in the presence of FA, PFOS
      absorption was reduced and the promotion effect of GO on PFOS accumulation was
      remitted.

PMID- 27718558
TI  - A Novel Methodology for Bioenergetic Analysis of Plasmodium falciparum Reveals a
      Glucose-Regulated Metabolic Shift and Enables Mode of Action Analyses of
      Mitochondrial Inhibitors.
AB  - Given that resistance to all drugs in clinical use has arisen, discovery of new
      antimalarial drug targets is eagerly anticipated. The Plasmodium mitochondrion
      has been considered a promising drug target largely based on its significant
      divergence from the host organelle as well as its involvement in ATP production
      and pyrimidine biosynthesis. However, the functions of Plasmodium mitochondrial
      protein complexes and associated metabolic pathways are not fully characterized.
      Here, we report the development of novel and robust bioenergetic assay protocols
      for Plasmodium falciparum asexual parasites utilizing a Seahorse Bioscience XFe24
      Extracellular Flux Analyzer. These protocols allowed us to simultaneously assess
      the direct effects of metabolites and inhibitors on mitochondrial respiration and
      glycolytic activity in real-time with the readout of oxygen consumption rate and
      extracellular acidification rate. Using saponin-freed parasites at the schizont
      stage, we found that succinate, malate, glycerol-3-phosphate, and glutamate, but
      not pyruvate, were able to increase the oxygen consumption rate and that glycerol
      3-phosphate dehydrogenase had the largest potential as an electron donor among
      tested mitochondrial dehydrogenases. Furthermore, we revealed the presence of a
      glucose-regulated metabolic shift between oxidative phosphorylation and
      glycolysis. We measured proton leak and reserve capacity and found bioenergetic
      evidence for oxidative phosphorylation in erythrocytic stage parasites but at a
      level much lower than that observed in mammalian cells. Lastly, we developed an
      assay platform for target identification and mode of action studies of
      mitochondria-targeting antimalarials. This study provides new insights into the
      bioenergetics and metabolomics of the Plasmodium mitochondria.

PMID- 27718560
TI  - Highly Enantioselective Allylic C-H Alkylation of Terminal Olefins with Pyrazol-5
      ones Enabled by Cooperative Catalysis of Palladium Complex and Bronsted Acid.
AB  - A highly enantioselective allylic C-H alkylation reaction of allylarenes with
      pyrazol-5-ones has been established by the cooperative catalysis of a chiral
      palladium complex and chiral Bronsted acid to afford a wide spectrum of
      functionalized chiral N-heterocycles with an all-carbon quaternary stereogenic
      center in high yields and with high levels of enantioselectivity (up to 96% ee),
      wherein the chiral ligand and phosphoric acid showed synergistic effect on the
      control of stereoselectivity. In addition, a palladium-catalyzed asymmetric
      allylic C-H alkylation of 1,4-pentadienes with pyrazol-5-ones has been realized
      to furnish highly functionalized pyrazol-5-ones in high enantioselectivities. In
      this case, the chiral ligand controls the stereoselectivity while the achiral
      Bronsted acid, 2-fluorobenzoic acid, turns out to be a better cocatalyst than the
      chiral phosphoric acid. The installation of electron-deficient substituents at
      3,3'-positions of binaphthyl backbone of chiral phosphoramidites is actually
      beneficial to the allylic C-H oxidation due to their survival in the presence of
      quinone derivative oxidants. These allylic C-H alkylation reactions undergo
      smoothly under mild conditions and tolerate a wide range of substrates. The
      resultant highly functionalized chiral pyrazol-5-ones have been applied to the
      preparation of more structurally diverse heterocycles by classical
      transformations.

PMID- 27718561
TI  - The Relevance of Oxygen for the Formation of Strecker Aldehydes during Beer
      Production and Storage.
AB  - Off-flavor in beer is often associated with the appearance of staling aldehydes.
      In this study, the factors amino acid concentration, carbohydrate concentration,
      Fe2+ concentration, and oxygen concentration were investigated in terms of their
      effect on the formation of carbonyl compounds during storage using response
      surface methodology. From all factors tested, only amino acid concentration and
      oxygen concentration promoted Strecker aldehyde formation during storage while
      all other carbonyls measured were unaffected. A mixture of glucose/xylose,
      representing carbohydrate sources, as well as Fe2+ concentration were
      insignificant factors; though, carbohydrate additions exhibited a significant
      role for the formation of 2-furfural. De novo formation of phenylacetaldehyde
      from phenylalanine during beer storage was observed using labeling experiments
      and a linear relationship between Strecker aldehydes formed and total packaged
      oxygen was identified. Capping beers with oxygen barrier crown corks and addition
      of 10 mg/L EDTA to beers effectively diminished Strecker aldehyde formation.
      Oxygen was additionally shown to significantly promote Strecker aldehyde
      formation during sweet wort production. A pathway for the reactive oxygen species
      induced degradation of amino acids yielding Strecker aldehydes was proposed and
      was further scrutinized in buffered model solutions. The insignificant role of
      Fe2+ in the response surface experiments is discussed.

PMID- 27718562
TI  - The Low-Temperature Conversion of Methane to Methanol on CeOx/Cu2O catalysts:
      Water Controlled Activation of the C-H Bond.
AB  - An inverse CeO2/Cu2O/Cu(111) catalyst is able to activate methane at room
      temperature producing C, CHx fragments and COx species on the oxide surface. The
      addition of water to the system leads to a drastic change in the selectivity of
      methane activation yielding only adsorbed CHx fragments. At a temperature of 450
      K, in the presence of water, a CH4 ? CH3OH catalytic transformation occurs with a
      high selectivity. OH groups formed by the dissociation of water saturate the
      catalyst surface, removing sites that could decompose CHx fragments, and
      generating centers on which methane can directly interact to yield methanol.

PMID- 27718563
TI  - Nuciferine Alleviates Renal Injury by Inhibiting Inflammatory Responses in
      Fructose-Fed Rats.
AB  - Nuciferine is a major active component from lotus leaf. This study examined the
      effects of nuciferine on fructose-induced renal injury and explored its possible
      mechanism. Rats consumed drinking water or 10% fructose for 12 wk. Fructose-fed
      rats were orally treated with water, or 7, 14 or 28 mg/kg nuciferine for the last
      6 wk. HK-2 cells were exposed to 5 mM fructose alone or in combination with
      nuciferine (2.5-40 MUM) for 24 h. Nuciferine significantly attenuated fructose
      induced hyperuricemia, dyslipidemia and systemic inflammation in rats. More
      importantly, it alleviated renal pathological injury with proteinuria at 20 and
      40 mg/kg (2.58 +/- 0.97 and 2.48 +/- 1.04 mg/mg.creatinine, P < 0.05) compared
      with fructose-vehicle group (4.10 +/- 1.18 mg/mg.creatinine). Furthermore,
      nuciferine reduced TLR4, MyD88, PI3K, ILK, p-AKT, p-P65 and NLRP3 inflammasome
      protein levels (P < 0.05 for all) in renal cortex of fructose-fed rats (14 and 28
      mg/kg), and fructose-exposed HK-2 cells (5-40 MUM), being consistent with its
      reduction of inflammatory cytokines IL-1beta, IL-6, TNF-alpha, and MCP-1 (P <
      0.05 for all) in vivo and in vitro. These findings suggested that nuciferine
      alleviated fructose-induced inflammation by inhibiting TLR4/PI3K/NF-kappaB
      signaling and NLRP3 inflammasome activation in rat renal cortex and HK-2 cells,
      which may contribute to the improvement of renal injury.

PMID- 27718564
TI  - 1,3-Dipolar Cycloaddition of Alkyne-Tethered N-Tosylhydrazones: Synthesis of
      Fused Polycyclic Pyrazoles.
AB  - A general and transition-metal-free access to the fused polycyclic pyrazoles via
      an intramolecular 1,3-dipolar cycloaddition reaction of alkyne-tethered
      tosylhydrazones has been reported. The pure solid products could be obtained
      without column chromatography in high to excellent yields, and the obtained
      products are useful bioactive molecules or could be used as the key intermediate
      for synthesis of these compounds in one or two steps. Additionally, a [3+2]
      cycloaddition followed by a direct H-shift aromatization reaction mechanism was
      proposed, which is different from the previously reported aryl or alkyl
      sequential [1,5]-sigmatropic rearrangement pathway.

PMID- 27718565
TI  - Microwave Plasma-Activated Chemical Vapor Deposition of Nitrogen-Doped Diamond.
      II: CH4/N2/H2 Plasmas.
AB  - We report a combined experimental and modeling study of microwave-activated
      dilute CH4/N2/H2 plasmas, as used for chemical vapor deposition (CVD) of diamond,
      under very similar conditions to previous studies of CH4/H2, CH4/H2/Ar, and N2/H2
      gas mixtures. Using cavity ring-down spectroscopy, absolute column densities of
      CH(X, v = 0), CN(X, v = 0), and NH(X, v = 0) radicals in the hot plasma have been
      determined as functions of height, z, source gas mixing ratio, total gas
      pressure, p, and input power, P. Optical emission spectroscopy has been used to
      investigate, with respect to the same variables, the relative number densities of
      electronically excited species, namely, H atoms, CH, C2, CN, and NH radicals and
      triplet N2 molecules. The measurements have been reproduced and rationalized from
      first-principles by 2-D (r, z) coupled kinetic and transport modeling, and
      comparison between experiment and simulation has afforded a detailed
      understanding of C/N/H plasma-chemical reactivity and variations with process
      conditions and with location within the reactor. The experimentally validated
      simulations have been extended to much lower N2 input fractions and higher
      microwave powers than were probed experimentally, providing predictions for the
      gas-phase chemistry adjacent to the diamond surface and its variation across a
      wide range of conditions employed in practical diamond-growing CVD processes. The
      strongly bound N2 molecule is very resistant to dissociation at the input MW
      powers and pressures prevailing in typical diamond CVD reactors, but its chemical
      reactivity is boosted through energy pooling in its lowest-lying (metastable)
      triplet state and subsequent reactions with H atoms. For a CH4 input mole
      fraction of 4%, with N2 present at 1-6000 ppm, at pressure p = 150 Torr, and with
      applied microwave power P = 1.5 kW, the near-substrate gas-phase N atom
      concentration, [N]ns, scales linearly with the N2 input mole fraction and exceeds
      the concentrations [NH]ns, [NH2]ns, and [CN]ns of other reactive nitrogen
      containing species by up to an order of magnitude. The ratio [N]ns/[CH3]ns scales
      proportionally with (but is 102-103 times smaller than) the ratio of the N2 to
      CH4 input mole fractions for the given values of p and P, but [N]ns/[CN]ns
      decreases (and thus the potential importance of CN in contributing to N-doped
      diamond growth increases) as p and P increase. Possible insights regarding the
      well-documented effects of trace N2 additions on the growth rates and
      morphologies of diamond films formed by CVD using MW-activated CH4/H2 gas
      mixtures are briefly considered.

PMID- 27718567
TI  - PbI2-HMPA Complex Pretreatment for Highly Reproducible and Efficient CH3NH3PbI3
      Perovskite Solar Cells.
AB  - Interfacial engineering of the meso-TiO2 surface through a modified sequential
      deposition procedure involving a novel PbI2-HMPA complex pretreatment is
      conducted as a reproducible method for preparing MAPbI3 based perovskite solar
      cells providing the highest efficiencies yet reported with the polymer HTM layer.
      Grazing-incidence X-ray diffraction depth profiling confirms the formation of a
      perovskite film with a PbI2-rich region close to the electron transport layer
      (ETL) due to the strong interaction of HMPA with PbI2, which successfully
      retarded the dissolution of the PbI2 phase when depositing the perovskite layer
      on top. These results are further confirmed by energy-dispersive X-ray
      spectroscopy performed in a scanning transmission electron microscope, which
      reveals that the I/Pb ratio in samples treated with the complex is indeed reduced
      in the vicinity of the ETL contact when compared to samples without the
      treatment. The engineered interface leads to an average power conversion
      efficiency of 19.2% (reverse scan, standard deviation SD < 0.2) over 30 cells
      (best cell at 19.5% with high FF of 0.80).

PMID- 27718566
TI  - Bubble-Free Propulsion of Ultrasmall Tubular Nanojets Powered by Biocatalytic
      Reactions.
AB  - The motion of self-propelled tubular micro- and nanojets has so far been achieved
      by bubble propulsion, e.g., O2 bubbles formed by catalytic decomposition of H2O2,
      which renders future biomedical applications inviable. An alternative self
      propulsion mechanism for tubular engines on the nanometer scale is still missing.
      Here, we report the fabrication and characterization of bubble-free propelled
      tubular nanojets (as small as 220 nm diameter), powered by an enzyme-triggered
      biocatalytic reaction using urea as fuel. We studied the translational and
      rotational dynamics of the nanojets as functions of the length and location of
      the enzymes. Introducing tracer nanoparticles into the system, we demonstrated
      the presence of an internal flow that extends into the external fluid via the
      cavity opening, leading to the self-propulsion. One-dimensional nanosize,
      longitudinal self-propulsion, and biocompatibility make the tubular nanojets
      promising for future biomedical applications.

PMID- 27718568
TI  - Superhard Rhenium/Tungsten Diboride Solid Solutions.
AB  - Rhenium diboride (ReB2), containing corrugated layers of covalently bonded boron,
      is a superhard metallic compound with a microhardness reaching as high as 40.5
      GPa (under an applied load of 0.49 N). Tungsten diboride (WB2), which takes a
      structural hybrid between that of ReB2 and AlB2, where half of the boron layers
      are planar (as in AlB2) and half are corrugated (as in ReB2), has been shown not
      to be superhard. Here, we demonstrate that the ReB2-type structure can be
      maintained for solid solutions of tungsten in ReB2 with tungsten content up to a
      surprisingly large limit of nearly 50 atom %. The lattice parameters for the
      solid solutions linearly increase along both the a- and c-axes with increasing
      tungsten content, as evaluated by powder X-ray and neutron diffraction. From
      micro- and nanoindentation hardness testing, all of the compositions within the
      range of 0-48 atom % W are superhard, and the bulk modulus of the 48 atom % solid
      solution is nearly identical to that of pure ReB2. These results further indicate
      that ReB2-structured compounds are superhard, as has been predicted from first
      principles calculations, and may warrant further studies into additional solid
      solutions or ternary compounds taking this structure type.

PMID- 27718569
TI  - Production and directional evolution of anti-sarafloxacin ScFv antibody for
      immunoassay of fluoroquinolones in milk.
AB  - A recombinant anti-sarafloxacin ScFv antibody was produced by direct
      transformation of its gene into Rosetta-gami(DE3) for expression, and then its
      recognition mechanisms for 12 fluoroquinolones were studied by using molecular
      docking method. Based on the results of virtual mutation, the ScFv antibody was
      evolved by directional mutagenesis of contact amino acid residue Tyr99 to His.
      The ScFv mutant showed highly increased affinity for the 12 drugs with up to 7
      folds improved sensitivity. Finally, the mutant was used to develop an indirect
      competitive enzyme linked immunosorbent assay for determination of the 12 drugs
      in milk. The limits of detection were in the range of 0.3-8.0 ng/mL, the
      crossreactivities were in the range of 5%-106%, and the recoveries from the
      standards fortified blank milk were in the range of 62.0%-89.3%. This is the
      first study reporting the evolution of a ScFv antibody by using directional
      mutagenesis strategy based on virtual mutation.

PMID- 27718570
TI  - Alcohols as Latent Coupling Fragments for Metallaphotoredox Catalysis: sp3-sp2
      Cross-Coupling of Oxalates with Aryl Halides.
AB  - Alkyl oxalates, prepared from their corresponding alcohols, are engaged for the
      first time as carbon radical fragments in metallaphotoredox catalysis. In this
      report, we demonstrate that alcohols, native organic functional groups, can be
      readily activated with simple oxalyl chloride to become radical precursors in a
      net redox-neutral Csp3-Csp2 cross-coupling with a broad range of aryl halides.
      This alcohol-activation coupling is successfully applied to the functionalization
      of a naturally occurring steroid and the expedient synthesis of a medicinally
      relevant drug lead.

PMID- 27718571
TI  - Assessment of DFT Functionals for QTAIM Topological Analysis of Halogen Bonds
      with Benzene.
AB  - Halogen bonding, a noncovalent interaction between a halogen atom and a
      nucleophilic site, is receiving a growing attention in the chemical community
      stimulating a large number of theoretical investigations. The density functional
      theory (DFT) approach revealed to be one of the most suitable methods owing to
      its accuracy and low computational cost. We report here a detailed analysis of
      the performance of an extensive set of DFT functionals in reproducing accurate
      binding energies and topological properties for the halogen-bonding interaction
      of either NCX or PhX molecules (X = F, Cl, Br, I) with the aromatic system of
      benzene in the T-shaped configuration. It was found that the better performance
      for both sets of properties is provided by a small subset of functionals able to
      take into account, implicitly or explicitly (by inclusion of an additive pairwise
      potential), the dispersion contribution, that is, omegaB97X, M06-2X, M11,
      mPW2PLYP-D, and B2PLYP-D3.

PMID- 27718572
TI  - Amino Acid Specific Effects on RNA Tertiary Interactions: Single-Molecule Kinetic
      and Thermodynamic Studies.
AB  - In light of the current models for an early RNA-based universe, the potential
      influence of simple amino acids on tertiary folding of ribozymal RNA into
      biochemically competent structures is speculated to be of significant
      evolutionary importance. In the present work, the folding-unfolding kinetics of a
      ubiquitous tertiary interaction motif, the GAAA tetraloop-tetraloop receptor (TL
      TLR), is investigated by single-molecule fluorescence resonance energy transfer
      spectroscopy in the presence of natural amino acids both with (e.g., lysine,
      arginine) and without (e.g., glycine) protonated side chain residues. By way of
      control, we also investigate the effects of a special amino acid (e.g., proline)
      and amino acid mimetic (e.g., betaine) that contain secondary or quaternary amine
      groups rather than a primary amine group. This combination permits systematic
      study of amino acid induced (or amino acid like) RNA folding dynamics as a
      function of side chain complexity, pKa, charge state, and amine group content.
      Most importantly, each of the naturally occurring amino acids is found to
      destabilize the TL-TLR tertiary folding equilibrium, the kinetic origin of which
      is dominated by a decrease in the folding rate constant (kdock), also affected by
      a strongly amino acid selective increase in the unfolding rate constant
      (kundock). To further elucidate the underlying thermodynamics, single-molecule
      equilibrium constants (Keq) for TL-TLR folding have been probed as a function of
      temperature, which reveal an amino acid dependent decrease in both overall
      exothermicity (DeltaDeltaH degrees  > 0) and entropic cost (-TDeltaDeltaS degrees
      < 0) for the overall folding process. Temperature-dependent studies on the
      folding/unfolding kinetic rate constants reveal analogous amino acid specific
      changes in both enthalpy (DeltaDeltaH?) and entropy (DeltaDeltaS?) for accessing
      the transition state barrier. The maximum destabilization of the TL-TLR tertiary
      interaction is observed for arginine, which is consistent with early studies of
      arginine and guanidine ion-inhibited self-splicing kinetics for the full
      Tetrahymena ribozyme [ Yarus , M. ; Christian , E. L. Nature 1989 , 342 , 349 -
      350 ; Yarus , M. Science 1988 , 240 , 1751 - 1758 ].

PMID- 27718575
TI  - Synthesis of Substituted 1,4-Dioxenes through O-H Insertion and Cyclization Using
      Keto-Diazo Compounds.
AB  - 1,4-Dioxenes present interesting potential as synthetic intermediates and as
      unusual motifs for incorporation into biologically active compounds. Here, an
      efficient synthesis of functionalized 1,4-dioxenes is achieved in two steps.
      Using keto-diazo compounds, a ruthenium catalyzed O-H insertion with beta
      halohydrins followed by treatment with base results in cyclization with excellent
      selectivity, through O-alkylation of the keto-enolate. A variety of halohydrins
      and anion-stabilizing groups in the diazo-component are tolerated, affording
      novel functionalized dioxenes. Enantioenriched beta-bromohydrins provide
      enantioenriched 1,4-dioxenes.

PMID- 27718574
TI  - Benzoxazinoids in Prostate Cancer Patients after a Rye-Intensive Diet: Methods
      and Initial Results.
AB  - Rye bread contains high amounts of benzoxazinoids, and in vitro studies have
      shown suppressive effects of selected benzoxazinoids on prostate cancer cells.
      Thus, research into benzoxazinoids as possible suppressors of prostate cancer is
      demanded. A pilot study was performed in which ten prostate cancer patients
      received a rye-enriched diet 1 week prior to prostatectomy. Plasma and urine
      samples were collected pre- and postintervention. Ten prostate biopsies were
      obtained from each patient and histologically evaluated. The biopsies exhibited
      concentrations above the detection limit of seven benzoxazinoids ranging from
      0.15 to 10.59 ng/g tissue. An OPLS-DA analysis on histological and plasma
      concentrations of benzoxazinoids classified the subjects into two clusters. A
      tendency of higher benzoxazinoid concentrations toward the benign group
      encourages further investigations. Benzoxazinoids were quantified by an optimized
      LC-MS/MS method, and matrix effects were evaluated. At low concentrations in
      biopsy and plasma matrices the matrix effect was concentration-dependent and
      nonlinear. For the urine samples the general matrix effects were small but
      patient-dependent.

PMID- 27718573
TI  - Antitumor Activity of Lankacidin Group Antibiotics Is Due to Microtubule
      Stabilization via a Paclitaxel-like Mechanism.
AB  - Lankacidin group antibiotics show strong antimicrobial activity against various
      Gram-positive bacteria. In addition, they were shown to have considerable
      antitumor activity against certain cell line models. For decades, the antitumor
      activity of lankacidin was associated with the mechanism of its antimicrobial
      action, which is interference with peptide bond formation during protein
      synthesis. This, however, was never confirmed experimentally. Due to significant
      similarity to paclitaxel-like hits in a previous computational virtual screening
      study, we suggested that the cytotoxic effect of lankacidin is due to a
      paclitaxel-like action. In this study, we tested this hypothesis computationally
      and experimentally and confirmed that lankacidin is a microtubule stabilizer that
      enhances tubulin assembly and displaces taxoids from their binding site. This
      study serves as a starting point for optimization of lankacidin derivatives for
      better antitumor activities. It also highlights the power of computational
      predictions and their aid in guiding experiments and formulating rigorous
      hypotheses.

PMID- 27718576
TI  - Revisiting the Dielectric Constant Effect on the Nucleophile and Leaving Group of
      Prototypical Backside Sn2 Reactions: a Reaction Force and Atomic Contribution
      Analysis.
AB  - The solvent effect on the nucleophile and leaving group atoms of the prototypical
      F- + CH3Cl -> CH3F + Cl- backside bimolecular nucleophilic substitution reaction
      (SN2) is analyzed employing the reaction force and the atomic contributions
      methods on the intrinsic reaction coordinate (IRC). Solvent effects were
      accounted for using the polarizable continuum solvent model. Calculations were
      performed employing eleven dielectric constants, epsilon, ranging from 1.0 to
      78.5, to cover a wide spectrum of solvents. The reaction force data reveals that
      the solvent mainly influences the region of the IRC preceding the energy barrier,
      where the structural rearrangement to reach the transition state occurs. A
      detailed analysis of the atomic role in the reaction as a function of epsilon
      reveals that the nucleophile and the carbon atom are the ones that contribute the
      most to the energy barrier. In addition, we investigated the effect of the choice
      of nucleophile and leaving group on the DeltaE0 and DeltaE? of Y- + CH3X -> YCH3
      + X- (X,Y= F, Cl, Br, I) in aqueous solution. Our analysis allowed us to find
      relationships between the atomic contributions to the activation energy and
      leaving group ability and nucleophilicity.

PMID- 27718578
TI  - Synthesis, Structure, and Reactivity of a Cylinder-Shaped
      Cyclo[12]orthophenylene[6]ethynylene: Toward the Synthesis of Zigzag Carbon
      Nanobelts.
AB  - Benzannulated cyclacenes (BCs) have been proposed as stable zigzag carbon
      nanobelts. Density functional theory (DFT) calculations revealed a closed-shell
      ground state for [12]BC, whereas an open-shell ground state was suggested for
      [12]cyclacene. The calculated strain energy and frontier molecular orbital
      energies of [12]BC also implied high stability. An unstrained macrocycle 1,
      consisting of orthophenylene and ethynylene moieties, was designed as a potential
      precursor for [12]BC and synthesized by sequential Suzuki-Miyaura cross-coupling
      of diphenylacetylene derivatives. While the conversion of 1 into [12]BC is still
      under investigation, an unexpected rearrangement of the triene moieties in 1,
      affording a tribenzo[f,k,m]tetraphene structure, was discovered during the
      screening of reaction conditions. An attempt was made to rationalize this result
      by proposing a plausible reaction mechanism that proceeds via intermediates
      containing cyclobutadiene or Dewar benzene moieties. The proposed mechanism is
      partially supported by DFT calculations.

PMID- 27718577
TI  - Characterization of Nitric Oxide Modulatory Activities of Alkaline-Extracted and
      Enzymatic-Modified Arabinoxylans from Corn Bran in Cultured Human Monocytes.
AB  - The ingestion of foods and food-derived substances that may mediate the immune
      system is widely studied. Evidence suggests cereal arabinoxylans (AXs) have
      immunomodulatory activities that may impart health benefits in terms of immune
      enhancement. This study extracted AXs from corn bran using alkali and developed a
      modification process using three endoxylanases to obtain fractions of lower
      molecular weight ranges. In vitro studies showed extracted and modified AXs
      significantly (P < 0.05) elevated nitric oxide (NO) synthesis by the human U937
      monocytic cell line (ranging from 53.7 +/- 1.1 to 62.9 +/- 1.2 MUM per million
      viable cells) at all concentrations tested (5-1000 MUg/mL), indicative of immune
      enhancement compared to an untreated control (43.7 +/- 1.9 MUM per million viable
      cells). The study suggested the dose range and Mw distribution of AXs are key
      determinants of immune-modulatory activity. AXs in the low Mw range (0.1-10 KDa)
      were the most effective at inducing NO secretion by U937 macrophages at low AX
      concentration ranges (5-50 MUg/mL), with NO production peaking at 62.9 +/- 1.2
      MUM per million viable cells with 5 MUg/mL of AX (P = 0.0009). In contrast, AXs
      in the high Mw range (100-794 kDa) were most effective at inducing NO at high AX
      concentration ranges (500-1000 MUg/mL) with NO production reaching a maximum of
      62.7 +/- 1.3 MUM per million viable cells at 1000 MUg/mL of AX (P = 0.0011). The
      findings suggest that dietary AXs from corn bran may heighten innate immune
      responses in the absence of infection or disease.

PMID- 27718579
TI  - Superior Catalytic Performance of Gold Nanoparticles Within Small Cross-Linked
      Lysozyme Crystals.
AB  - Bionanomaterials synthesized by bio-inspired templating methods have emerged as a
      novel class of composite materials with varied applications in catalysis,
      detection, drug delivery, and biomedicine. In this study, two kinds of cross
      linked lysozyme crystals (CLLCs) of different sizes were applied for the in situ
      growth of Au nanoparticles (AuNPs). The resulting composite materials were
      characterized by light microscopy, scanning electron microscopy, transmission
      electron microscopy, thermogravimetric analysis, and X-ray photoelectron
      spectroscopy. The catalytic properties of the prepared materials were examined in
      the catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). It was
      found that the size of the AuNPs increased with an increase in Au loading for
      both small and large crystals. In addition, small crystals favored homogeneous
      adsorption and distribution of the metal precursors. And the size of the AuNPs
      within small crystals could be maintained below 2.5 nm by managing the
      HAuCl4/lysozyme molar ratio. Furthermore, the lysozyme functional groups blocked
      the AuNP activity sites, therefore reducing their catalytic activity. This effect
      was more pronounced for small AuNPs. Moreover, the mass transfer of reactants (4
      NP) from solution to AuNPs within the crystals restricted their catalytic
      reduction, leading to superior catalytic performance of the AuNPs within small
      cross-linked lysozyme crystals (Au@S-CLLCs) compared to those within large cross
      linked lysozyme crystals (Au@L-CLLCs) at similar Au loadings. Finally, an
      increase in Au loading clogged the crystal channels with increased quantities of
      larger aggregated AuNPs, thus impeding the catalytic performance of Au@S-CLLCs.

PMID- 27718580
TI  - Comparative proteomics implicates a role for multiple secretion systems in
      electrode-respiring Geobacter sulfurreducens biofilms.
AB  - Geobacter sulfurreducens is a dissimilatory metal-reducing bacterium capable of
      forming thick electron-conducting biofilms on solid electrodes. Here, we employ
      for the first time comparative proteomics to identify key physiological changes
      involved in G. sulfurreducens adaptation from fumarate-respiring planktonic cells
      to electron-conducting biofilms. Increased levels of proteins involved in outer
      membrane biogenesis, cell motility and secretion are expressed in biofilms. Of
      particular importance to the electron-conducting biofilms are proteins associated
      with secretion systems of Type I, II, V and Type IV pili. Furthermore, enzymes
      involved in lipopolysaccharide and peptidoglycan biosynthesis show increased
      levels of expression in electron-conducting biofilms compared to planktonic
      cells. These observations point to similarities in long-range electron transfer
      mechanisms between G. sulfurreducens and Shewanella oneidensis, while
      highlighting the wider significance of secretion systems beyond that of Type IV
      pili identified to date in the adaptation of G. sulfurreducens to electrode
      respiration.

PMID- 27718581
TI  - Copper-Mediated Radiofluorination of Arylstannanes with [18F]KF.
AB  - A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with
      [18F]KF is described. This method is fast, uses commercially available reagents,
      and is compatible with both electron-rich and electron-deficient arene
      substrates. This method has been applied to the manual synthesis of a variety of
      clinically relevant radiotracers including protected [18F]F-phenylalanine and
      [18F]F-DOPA. In addition, an automated synthesis of [18F]MPPF is demonstrated
      that delivers a clinically validated dose of 200 +/- 20 mCi with a high specific
      activity of 2400 +/- 900 Ci/mmol.

PMID- 27718582
TI  - All-Printed Differential Temperature Sensor for the Compensation of Bending
      Effects.
AB  - Because printed resistance temperature detectors (RTDs) are affected by tension
      and compression of metallic patterns on flexible or curved surfaces, a
      significant temperature-sensing error occurs in general. Hence, we propose a
      differential temperature sensor (DTS) to compensate the bending effect of the
      printed RTDs, which is composed of two serially connected similar meander
      patterns fabricated back-to-back on a polyimide polyethylene terephthalate
      substrate through a Dimatix DMP-3000 inkjet printer using silver nanoparticles.
      Under mechanical deformation, the resistance of the proposed DTS is not varied
      significantly under the same temperature environment because its patterns vary
      differentially as one side experiences tension while the opposite side
      experiences compression. A single meander pattern of the proposed DTS has a total
      length of 75 mm and device dimensions of 7 * 7 mm2. The total resistance
      variation is observed to be 15.5 Omega against the temperature variation from 0
      to 100  degrees C, and the temperature coefficient of resistance is 1.076 * 10-3 
      degrees C-1. The proposed DTS exhibits no significant resistance change on
      bendability testing down to 2 mm diameter because of mechanical deformation. In
      addition, it is also used to detect the curvature of a body shape down to 2 mm
      diameter because its resistance changes by +/-8.22% using a single meander
      pattern of DTS. The proposed sensor can be applied on a curved or flexible
      surface to measure relatively accurate temperature when compared to a single
      meander pattern.

PMID- 27718583
TI  - Hitorins A and B, Hexacyclic C25 Terpenoids from Chloranthus japonicus.
AB  - Two novel C25 terpenoids with a 6/5/5/5/5/3 hexacyclic skeleton including one
      gamma-lactone ring and two tetrahydrofuran rings, hitorins A (1) and B (2), were
      isolated from the aerial parts of Chloranthus japonicus. The structures of 1 and
      2 were elucidated on the basis of spectroscopic analyses as well as TDDFT ECD
      calculations. Hitorins A (1) and B (2) might be biogenetically derived from
      eudesmane sesquiterpene and thujane monoterpene.

PMID- 27718584
TI  - Indole-to-Carbazole Strategy for the Synthesis of Substituted Carbazoles under
      Metal-Free Conditions.
AB  - An efficient indole-to-carbazole strategy has been developed under metal-free
      conditions. This carbazole formation was highly promoted by NH4I with high
      regioselectivity through formal [2 + 2 + 2] annulation of indoles, ketones, and
      nitroolefins. It thus conveniently enabled the assembly of a large number of
      diversified carbazole products with good tolerance of a broad range of functional
      groups.

PMID- 27718585
TI  - Transamination at the Crossroad of the One-Pot Synthesis of N-Substituted
      Quinonediimines and C-Substituted Benzobisimidazoles.
AB  - A green and very efficient synthesis of N-substituted benzoquinonediimines or C
      substituted benzo-bis(imidazole) derivatives is described under similar
      conditions. The different reaction pathway is only controlled by the nature of
      the primary amines, which tunes the reactivity of the intermediates.

PMID- 27718586
TI  - Enantioselective Protonation of Silyl Enol Ether Using Excited State Proton
      Transfer Dyes.
AB  - Enantiopure excited state proton transfer (ESPT) dyes were used for the
      asymmetric protonation of silyl enol ether. Under 365 nm irradiation, with 3,3'
      dibromo-VANOL as the ESPT dye, up to 49% enantioselectivity with a 68% yield of
      product was observed at room temperature. The reaction is effective with a range
      of silyl enol ethers and can also be achieved with visible light upon the
      addition of triplet sensitizer. The relatively low ee of the protonated product
      is due to the racemization/decomposition of the ESPT dye in the excited state as
      indicated by circular dichroism, HPLC, and UV-vis spectroscopy.

PMID- 27718587
TI  - Adsorption of Human Plasma Albumin and Fibronectin onto Nanostructured Black
      Silicon Surfaces.
AB  - The protein adsorption of two human plasma proteins-albumin (Alb) and fibronectin
      (Fn)-onto synthetic nanostructured bactericidal material-black silicon (bSi)
      surfaces (that contain an array of nanopillars) and silicon wafer (nonstructured)
      surfaces-was investigated. The adsorption behavior of Alb and Fn onto two types
      of substrata was studied using a combination of complementary analytical
      techniques. A two-step Alb adsorption mechanism onto the bSi surface has been
      proposed. At low bulk concentrations (below 40 MUg/mL), the Alb preferentially
      adsorbed at the base of the nanopillars. At higher bulk concentrations, the Alb
      adsorbed on the top of the nanopillars. In the case of Fn, the protein
      preferentially adsorbed on the top of the nanopillars, irrespective of its bulk
      concentration.

PMID- 27718588
TI  - Probing the Influence of Dielectric Environment on Excitons in Monolayer WSe2:
      Insight from High Magnetic Fields.
AB  - Excitons in atomically thin semiconductors necessarily lie close to a surface,
      and therefore their properties are expected to be strongly influenced by the
      surrounding dielectric environment. However, systematic studies exploring this
      role are challenging, in part because the most readily accessible exciton
      parameter-the exciton's optical transition energy-is largely unaffected by the
      surrounding medium. Here we show that the role of the dielectric environment is
      revealed through its systematic influence on the size of the exciton, which can
      be directly measured via the diamagnetic shift of the exciton transition in high
      magnetic fields. Using exfoliated WSe2 monolayers affixed to single-mode optical
      fibers, we tune the surrounding dielectric environment by encapsulating the
      flakes with different materials and perform polarized low-temperature magneto
      absorption studies to 65 T. The systematic increase of the exciton's size with
      dielectric screening, and concurrent reduction in binding energy (also inferred
      from these measurements), is quantitatively compared with leading theoretical
      models. These results demonstrate how exciton properties can be tuned in future
      2D optoelectronic devices.

PMID- 27718589
TI  - Increased glucose utilization and cell growth of Corynebacterium glutamicum by
      modifying the glucose-specific phosphotransferase system (PTSGlc) genes.
AB  - The phosphoenolpyruvate:glucose phosphotransferase system (PTSGlc) is the major
      pathway of glucose uptake in Corynebacterium glutamicum. This study investigated
      glucose consumption rate, cell growth, and metabolite changes resulting from
      modification of PTSGlc. The classical l-lysine producer C. glutamicum XQ-8
      exhibited low glucose consumption, cell growth, and l-lysine production rates,
      whereas these parameters were significantly increased during cultivating on
      glucose plus maltose, through inactivation of SugR, or by overexpression of
      PTSGlc genes. XQ-8sugR::cat/pDXW-8-ptsI exhibited the highest increase in glucose
      consumption, growth rate, and l-lysine production, followed by XQ-8sugR::cat/pDXW
      8-ptsG. However, overexpression of ptsH had little effect on the above-mentioned
      factors. Although co-overexpression of ptsGHI led to the highest glucose
      consumption, growth rate, and final l-lysine production; the l-lysine production
      rate was lower than that of XQ-8sugR::cat/pDXW-8-ptsIH. In fed-batch
      fermentation, XQ-8sugR::cat/pDXW-8-ptsIH had a higher growth rate of 0.54 h-1 to
      a dry cell mass of 66 g.L-1 after 16 h, and had a higher l-lysine production rate
      of 159.2 g.L-1 after 36 h. These results indicate that modification of the sugar
      transport systems improves amino acid production, especially for mutants obtained
      by repeated physical and (or) chemical mutagenesis. However, modification of
      these systems needs to be performed on a case-by-case basis.

PMID- 27718590
TI  - Experiences With and Perceptions of Workplace Bullying Among Athletic Trainers in
      the Secondary School Setting.
AB  - CONTEXT: Workplace bullying (WPB) has recently received much attention in
      society. Research on WPB in athletic training practice settings is limited.
      OBJECTIVE: To determine the prevalence of WPB in the secondary school setting and
      explore the factors related to it. DESIGN: Mixed-methods study. SETTING:
      Secondary school. PATIENTS OR OTHER PARTICIPANTS: A total of 567 athletic
      trainers (women = 322 [56.8%], men = 245 [43.2%]), aged 36.5 +/- 11.1 years with
      11.9 +/- 9.5 years of experience took part in phase I. Ten participants (7 women
      and 3 men), aged 39.3 +/- 10.1 years with 14.3 +/- 8.3 years of experience, took
      part in phase II. DATA COLLECTION AND ANALYSIS: For the online survey, we used
      the previously validated and reliable (Cronbach alpha = .84) Athletic Training
      Workplace Environment Survey, which included the Negative Acts Questionnaire
      Revised. The prevalence of WPB was measured with descriptive statistics, and chi2
      analyses were used to compare differences between groups (ie, females and males,
      perpetrators' titles). The interview data were examined using an inductive
      content analysis. RESULTS: Of the participants, 44 (7.8%) were empirically
      identified as targets of bullying, though a higher percentage (12.4%, n = 70)
      self-identified as bullying targets. Men and women did not differ with respect to
      having experienced WPB, but more perpetrators were male (71.6%, n = 48) than
      female (28.4%, n = 19; chi21 = 12.55, P = <.001). We also observed a difference
      in perpetrators' titles, with the vast majority of bullies being coaches or
      administrators (chi26 = 33.82, P = <.001). Lack of administrator support and
      discrimination were antecedents of bullying. Stress, depression, and sleep
      disturbances were reported consequences. Participants coped with bullying by
      avoidance and role refocusing. CONCLUSIONS: Bullying was experienced by a small
      percentage of athletic trainers in the secondary school setting, a contrast to
      the findings in the collegiate practice setting.

PMID- 27718591
TI  - Probiotic Lactobacillus casei expressing porcine antimicrobial peptide PR39
      elevates antibacterial activity in the gastrointestinal tract.
AB  - PR39, a 4.7 kDa proline-rich antimicrobial peptide, acts as a cationic host
      defense peptide. In addition to killing bacteria, PR39 mediates inflammatory
      reactions, including cell proliferation, migration, wound healing, and
      angiogenesis. Here, we examined the antibacterial effects of this peptide. The
      synthetic gene fragment PR39 was inserted into the secretory expression vector
      plasmid pPG:612 of Lactobacillus casei, yielding the recombinant strain pPG:612
      PR39/L. casei 393. In vitro antibacterial tests showed that expression of the
      PR39 peptide in recombinant L. casei resulted in antibacterial activity against
      Escherichia coli and Salmonella but had only minor antibacterial effects in
      Staphylococcus aureus. In addition, BALB/c mice fed the recombinant pPG:612
      PR39/L. casei 393 grew better and had increased peripheral blood lymphocyte
      percentages, white blood cell numbers, and spleen indices than mice in the
      control group. Scanning electron microscopy showed that jejunum and duodenum
      villus height, crypt depth, and the ratio of villus height/crypt depth in the
      intestinal villi also increased. Moreover, mice fed the recombinant strain showed
      significantly lower mortality rates than the control group mice when challenged
      with the enterotoxigenic E. coli K88+. Thus, this recombinant expression system
      had the beneficial characteristics of both L. casei and PR39, supporting its
      potential as an animal feed additive.

PMID- 27718593
TI  - Responsible behaviour.
AB  - I read with interest in a news article last month details of Andy Burnham's
      recent experiences as health minister (Emergency Nurse, February).

PMID- 27718595
TI  - ?
AB  - Focus on care: emergency care staff at Coventry's new University Hospital have
      been chosen to star in a TV series being produced for the Discovery Channel. The
      documentary series, which will be shown this spring, will showcase emergency
      nurses and other specialist healthcare staff who care for more than 100,000
      patients a year. The cameras will follow patients from admission, through to
      diagnosis and treatment, and it is hoped that staff will give viewers an insight
      into the emergency care provided at the hospital. Pictured left to right, being
      filmed by director Kirsty Poskitt, are support worker Carol Ross, staff grade
      doctor Matt Robbins and cardiac nurse Celia Willmott.

PMID- 27718596
TI  - Web scan.
AB  - This selection of sites is intended for emergency nurses who are developing
      advanced skills, and for those who are teaching and coaching others.

PMID- 27718592
TI  - Whole-lesion apparent diffusion coefficient (ADC) metrics as a marker of breast
      tumour characterization-comparison between ADC value and ADC entropy.
AB  - OBJECTIVE: To prospectively assess the role of whole-lesion apparent diffusion
      coefficient (ADC) metrics in the characterization of breast tumours by comparing
      ADC value with ADC entropy. METHODS: 49 patients with 53 breast lesions underwent
      phased-array breast coil 1.5-T MRI. Two radiologists experienced in breast MRI,
      blinded to the final diagnosis, reviewed the ADC maps and placed a volume of
      interest on all slices including each lesion on the ADC map to obtain whole
      lesion mean ADC value and ADC entropy. The mean ADC value and ADC entropy in
      benign and malignant lesions were compared by the Mann-Whitney U-test. Receiver
      operating characteristic analysis was performed to assess the sensitivity and
      specificity of the two variables in the characterization of the breast lesions.
      RESULTS: The benign (n = 19) and malignant lesions (n = 34) had mean diameters of
      20.8 mm (10.1-31.5 mm) and 26.4 mm (10.5-42.3 mm), respectively. The mean ADC
      value of the malignant lesions was significantly lower than that of the benign
      ones (0.87 * 10-3 vs 1.49 * 10-3 mm2 s-1; p < 0.0001). Malignant ADC entropy was
      higher than benign entropy, without reaching levels of statistical significance
      (5.4 vs 5.0; p = 0.064). At a mean ADC cut-off value of 1.16 * 10-3 mm2 s-1, the
      sensitivity and specificity for diagnosing malignancy became optimal (97.1% and
      93.7, respectively) with an area under the curve (AUC) of 0.975. With regard to
      ADC entropy, the sensitivity and specificity at a cut-off of 5.18 were 67.6 and
      68.7%, respectively, with an AUC of 0.664. CONCLUSION: Whole-lesion mean ADC
      could be a helpful index in the characterization of suspicious breast lesions,
      with higher sensitivity and specificity than ADC entropy. Advances in knowledge:
      Two separate parameters of the whole-lesion histogram were compared for their
      diagnostic accuracy in characterizing breast lesions. Mean ADC was found to be
      able to characterize breast lesions, whereas entropy proved to be unable to
      differentiate benign from malignant breast lesions. It is, however, likely that
      entropy may distinguish these two groups if a larger cohort were used, or the
      fact that this may be influenced by the molecular subtypes of breast cancers
      included.

PMID- 27718598
TI  - New guidelines for managing patients with burns.
AB  - Emergency nurses can now access guidelines endorsed by the European Burns
      Association on managing patients who have partial thickness burns.

PMID- 27718597
TI  - Pain: a multifaceted phenomenon.
AB  - Pain is a multifaceted phenomenon. Simply asking patients if they have pain
      cannot be classed as a thorough assessment and is unlikely to give practitioners
      the information they need to make clinical decisions.

PMID- 27718599
TI  - ?
AB  - Mistaken identity: most patients attending emergency departments in the belief
      that they have consumed 'spiked' drinks actually test negative for drugs of
      misuse, according to research published last month in the Emergency Medicine
      Journal. The researchers, from Wrexham Maelor Hospital, say that the symptoms of
      such attenders are more likely to be caused by excessive intake of alcohol. For
      further details, access http://emj.bmj.com/.

PMID- 27718601
TI  - Call for emergency networks to improve children's care.
AB  - The Healthcare Commission has suggested that emergency care networks should be
      developed to help NHS organisations provide better care for children in A&E.

PMID- 27718600
TI  - The unique role of emergency nurses.
AB  - What is it that nurses do? What is their unique contribution to patient care?
      These questions were posed to me by emergency nursing consultant Gary Jones at
      the RCN Emergency Care Association conference last November, in a discussion
      about some of the articles published in Emergency Nurse.

PMID- 27718602
TI  - AMBEX places.
AB  - The Ambulance Service Association (ASA) is offering 20 subsidised places for
      emergency nurses to attend its annual conference and exhibition this year, AMBEX
      2007. The three-day conference is in Harrogate and starts on June 27.

PMID- 27718604
TI  - Self Assessment in Limb X-ray Interpretation: Musculoskeletal trauma imaging of
      appendicular skeleton Self Assessment in Limb X-ray Interpretation:
      Musculoskeletal trauma imaging of appendicular skeleton K Sakthivel-Wainford M&K
      Update Ltd 200 L29.00 978 1 905539 13 0 1905539134 [Formula: see text].
AB  - It's good to see the publication of another radiograph interpretation book
      because it reflects the exciting and continued role developments in both
      radiography and advanced nursing practice, and this one provides a good starting
      point for emergency nurses who are new to the challenges of trauma
      interpretation.

PMID- 27718603
TI  - The right to refuse.
AB  - Accepting or refusing clinical treatment is an adult's right, and guidance for
      healthcare professionals on the issue is set out in the Reference Guide to
      Consent for Examination or Treatment ( Department of Health 2001 ).

PMID- 27718605
TI  - Dentofacial traits in association with lower incisor alveolar cancellous bone
      thickness: A multiple regression analysis.
AB  - OBJECTIVE: To identify dentofacial anatomic traits associated with lower incisor
      cancellous bone thickness (LICBT) and then to assess their separate contributions
      and their combined contributions to the variation in LICBT. MATERIALS AND
      METHODS: A consecutive sample of cone beam computed tomography (CBCT) data taken
      in a university hospital within the same setting was retrospectively reviewed.
      Within the sample, CBCT data of 252 eligible subjects were reconstructed and
      measured for LICBT, facial traits, and mandibular symphyseal traits. A backward
      multiple linear regression was employed to explore the association between LICBT
      and seven representative dentofacial traits. RESULTS: Four dentofacial traits
      (vertical facial pattern, transverse jaw relationship, lower incisor cervical
      diameter, and mandibular symphyseal width) were identified as significantly
      associated with LICBT. The combination of these four factors could predict 64.3%
      of variations in LICBT (adjusted R2 = 0.643). Further comparison of LICBT among
      different transverse jaw relationships suggested that the LICBT of the normal
      (5.94 +/- 1.58 mm) group and the inferior convergent group (5.38 +/- 1.32 mm)
      were significantly larger than that of the crossbite group (4.34 +/- 1.27 mm) and
      the superior convergent group (4.53 +/- 1.67 mm). CONCLUSIONS: The bony support
      of lower incisors is significantly associated with several dentofacial traits.
      Reduced lower incisor bony support was statistically associated with increased
      vertical facial pattern, transverse jaw discrepancy, thinner mandibular
      symphyseal width, and smaller lower incisor cervical diameter.

PMID- 27718607
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27718608
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27718610
TI  - Advanced nurse practitioners.
AB  - Recent economic problems in Ireland have affected the ability of the Irish health
      service to recruit and retain medical staff. Recent increases to its population
      have led investigators to compare the advanced nurse practitioners (ANP) role in
      Ireland with those in the UK and United States.

PMID- 27718606
TI  - Comparative effects of piperine and simvastatin in fat accumulation and
      antioxidative status in high fat-induced hyperlipidemic rats.
AB  - The present study investigated the comparative effects of piperine (PIP) - the
      active ingredient of black and long peppers - and simvastatin (SIM) on hepatic
      steatosis in hyperlipidemic rats. Male Wistar rats were fed a cholesterol mixture
      daily by intragastric gavage for 8 weeks. Piperine was given by oral gavage 8 h
      after cholesterol feeding. The animals were divided into 4 groups: control, high
      fat (HF), high fat plus 40 mg PIP/kg, and high fat plus 2 mg SIM/kg. At the end
      of the treatment, liver cholesterol, triglyceride, thiobaribituric reacting
      substances, superoxide dismutase (SOD), serum aminotransferase (AST), and alanine
      transferase (ALT) were measured. The result demonstrated that PIP and SIM
      significantly reduced the accumulation of cholesterol, triglyceride, and lipid
      peroxidation in the liver, while elevation of SOD was observed. The activities of
      AST and ALT significantly decreased in PIP when compared with the HF group. Our
      in vitro study of pancreatic lipase also showed the inhibitory effect of PIP
      higher than 30% at 5 mmol/L. These results demonstrate that PIP has beneficial
      effects in the treatment and (or) prevention of fat accumulation in the liver and
      that this mechanism is due to the inhibition of pancreatic lipase and the
      improvement of oxidative status.

PMID- 27718609
TI  - Acute atrial fibrillation.
AB  - This study refers to the results of a prospective, single centre, randomised
      trial conducted over two years in the emergency department (ED) of Valduce
      Hospital, in Como, Italy. The hypothesis of the trial was that electrical
      cardioversion (EC) converts acute atrial fibrillation (AF) to sinus rhythm more
      effectively and safely than intravenous pharmacological cardioversion (PC).

PMID- 27718611
TI  - Deliberate self-harm.
AB  - This quantitative non-experimental descriptive survey refers to results from a
      self-administered postal questionnaire to measure emergency nurses' attitudes to
      deliberate self-harm. Defined as behaviour that may not be intended to cause
      death but is carried out in the knowledge that it is potentially harmful, self
      harm is said to include cutting, burning, attempted drowning, attempted hanging
      and self-poisoning.

PMID- 27718612
TI  - How to Master Nursing Calculations How to Master Nursing Calculations Chris
      Tyreman Kogan Page L9.99 176pp 9780749461553 0749461551 [Formula: see text].
AB  - THIS HANDY, inexpensive book starts with a short test to reveal numerical
      difficulties. It then covers a range of arithmetical problems to test the
      reader's ability and help him or her identify areas for development.

PMID- 27718613
TI  - Twenty years of excellence.
AB  - I WOULD like to congratulate all at Emergency Nurse for this, your 20th
      anniversary edition. To sustain the quality of the journal for so long is quite
      an achievement and your success should not be underestimated.

PMID- 27718614
TI  - Challenging and Emerging Conditions in Emergency Medicine Challenging and
      Emerging Conditions in Emergency Medicine Arvind Venkat Wiley-Blackwell L49.99
      376pp 9781905539611 1905539614 [Formula: see text].
AB  - INTENDED FOR doctors rather than nurses, this American text concerns how
      emergency care practitioners should treat people with challenging conditions such
      as geriatric trauma, congenital heart disease and cystic fibrosis. It also
      discusses the treatment of people who are morbidly obese or in chronic pain, and
      people with learning difficulties.

PMID- 27718616
TI  - Developing a world class NHS.
AB  - We nurses often complain that 'they' don't listen to us or even ask us our
      opinions about how services should be developed.

PMID- 27718617
TI  - ?
AB  - Virtually there: emergency care nurses may soon be able to hone their skills at
      multiple casualty incident triage using a new game based learning tool. The
      computer training programme is being developed by technology and consultancy
      company VEGA and 'serious game' developers TruSim. Learning consultant at VEGA,
      Steve Jarvis, said piloting of the tool should finish in February. 'It could
      offer emergency care staff a more engaging and flexible way of learning triage
      sieve,' he said.

PMID- 27718618
TI  - Drug information.
AB  - DrugScope is a massive UK resource site, at www.drugscope.org.uk , which contains
      information from more than 800 statutory and non-statutory sources, and provides
      reliable information on almost all aspects of drugs, their use and the harm they
      can cause.

PMID- 27718619
TI  - Three-point plan for older people's care.
AB  - Emergency nurses are being urged to adopt a three-point action plan for older
      people presenting with falls, confusion or hip fracture.

PMID- 27718620
TI  - Call for protocols for patients who refuse blood.
AB  - Emergency nurses and other care staff are being urged this month to consider the
      preparation of emergency care protocols for patients who decline blood
      transfusion.

PMID- 27718621
TI  - Drug talk.
AB  - Talk to Frank, at www.talktofrank.com , is a free and confidential 24-hour drug
      information service intended for young people. It offers clear factual
      information about drugs and offers help in finding services for families, friends
      and individuals.

PMID- 27718622
TI  - Reward emergency nurses 'appropriately', says RCN.
AB  - The RCN has called on The Scottish Government to ensure that emergency nurses are
      'appropriately rewarded, recognised, developed and enhanced'.

PMID- 27718623
TI  - Nurses to decide on resuscitation, guidelines suggest.
AB  - Emergency and other nurses should no longer be barred from deciding whether or
      not to continue cardiopulmonary resuscitation (CPR) attempts, according to new
      guidelines.

PMID- 27718625
TI  - Pain assessment.
AB  - The Children's Pain Assessment Project, at www.ich.ucl.ac.uk/cpap , is another
      good source of information about pain and pain relief.

PMID- 27718624
TI  - Board's eye view.
AB  - Over the past few years, negative media increased. coverage of nursing has
      steadily.

PMID- 27718626
TI  - Pain in children.
AB  - The Pain Sourcebook of Protocols, Policies and Pamphlets, at
      painsourcebook.ca/index.html , is the result of a collaboration by authors and
      contributors from around the world who have submitted guidance documents and
      booklets associated with pain.

PMID- 27718627
TI  - Substance abuse.
AB  - The Association of Nurses in Substance Abuse provides specialist advice, as well
      as information on conferences and training, for professionals working in the area
      of substance abuse.

PMID- 27718628
TI  - Renovated (nondual) approach to endometrial cancer typing: endocrine and
      inflammatory issues.

PMID- 27718631
TI  - Practice placements.
AB  - The clinical practice component of nurse training programmes accounts for a large
      part of students' education, and can shape their professional development and
      practice.

PMID- 27718630
TI  - Life-threatening Haemorrhage.
AB  - Haemorrhage is still a major cause of death in trauma patients, despite the
      advances in trauma care management. The Clinical Randomisation of an
      Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial results, which were
      published in 2010, show that tranexamic acid (TXA) reduces mortality in trauma
      patients with, or at risk of, bleeding, with no apparent increase in side
      effects.

PMID- 27718632
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27718633
TI  - Trauma preparation.
AB  - Emergency care practitioners often use a standard approach to advanced trauma
      life support involving oxygenation, ventilation and circulation. After successful
      resuscitation however, the challenge of care during the recovery phase is carried
      out by critical care nurses (CCNs).

PMID- 27718634
TI  - Drug calculations for nurses: context for practice Kerri Wright Drug Calculations
      for Nurses: Context for Practice Palgrave Macmillan L12.99 272pp 9780230231610
      0230231616 [Formula: see text].
AB  - THE AUTHOR of this comprehensive study guide is a senior lecturer at the school
      of health and social care at the University of Greenwich, who teaches drug
      calculation skills to nursing students. The book explains how nurses can
      calculate simple medicine dosages expressed as weight or volume strengths, and
      those used in continuous infusions.

PMID- 27718635
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27718636
TI  - Board's eye view.
AB  - IN 1992, when I was a member of the first Emergency Nurse editorial board, I had
      recently been appointed as a charge nurse. I was probably the most junior nurse
      on the team and, although my contributions from the clinical shop floor were
      welcomed, I was keen to learn from the more seasoned board members.

PMID- 27718637
TI  - New levothyroxine formulation meeting 95-105% specification over the whole shelf
      life: results from two pharmacokinetic trials.
AB  - OBJECTIVE: Small levothyroxine (L-T4) dose changes can lead to significant
      clinical effects. To ensure thyroid hormone levels are safely maintained,
      authorities are increasingly adopting stricter potency specifications for L-T4,
      the most stringent of these being 95-105% of the labeled dose over the whole
      shelf-life. Levothyroxine sodium (Euthyrox, Eutirox, Levothyrox ) has been
      reformulated, and two studies performed, to ensure bioequivalence to the
      currently marketed formulation and dosage form proportionality of the new
      formulation. METHODS: The bioequivalence study was an open-label, randomized,
      single-dose, two-period, two-sequence crossover comparing the highest dosage
      strengths of the currently marketed and the new L-T4 formulation at a total dose
      of 600 MUg. The dosage form proportionality study was an open-label, randomized,
      three-period, six-sequence crossover, comparing 50 MUg, 100 MUg, and 200 MUg L-T4
      tablets, at a total dose of 600 MUg. Blood samples were taken at predefined time
      intervals. Primary outcomes were area under the curve (AUC) and maximum
      concentration (Cmax) of thyroxine (T4) in plasma. RESULTS: In the bioequivalence
      study, comparing the T4 profiles for the new and current formulation of L-T4, the
      geometric least square mean ratio of the baseline-adjusted AUC0-72,adj was 99.3%
      (90% confidence interval [CI]: 95.6-103.2) and the Cmax,adj was 101.7% (90% CI:
      98.8-104.6). Bioequivalence was established if the 90% CI lay within the
      predefined 0.9-1.11 limits. In the dosage form proportionality study, pairwise
      comparisons ranged from 99.3% to 104.8%, and all 95% CIs were within the
      predefined CI range (0.8-1.25): the three dose strengths were dosage form
      proportional. CONCLUSIONS: The new formulation of L-T4 meets the most stringent
      potency specification guidelines, and has been demonstrated to be bioequivalent
      to the current formulation and to show dosage form proportionality. The new
      formulation will enable patients to receive a dose fine tuned to their medical
      needs, contributing to improved safety in the use of L-T4.

PMID- 27718638
TI  - SET protein overexpression contributes to paclitaxel resistance in MCF-7/S cells
      through PI3K/Akt pathway.
AB  - Patient SE translation (SET) is a carcinogen in facilitating cellular growth and
      proliferation, and promoting tumorigenesis and metastasis. The present study was
      to investigate the resistance mechanisms associated with SET in paclitaxel
      induced human breast cancer cells. The different expressions of SET, ATP-binding
      cassette (ABC) transporters and PI3K/Akt pathway between paclitaxel sensitive MCF
      7/S and paclitaxel resistant MCF-7/PTX cells were identified using western
      blotting. We adopted plasmid transfection to upregulate SET in MCF-7/S cells and
      a novel SET antagonist COG112 to decrease SET in MCF-7/PTX cells. Subsequently,
      cell viability to paclitaxel was assessed by MTT assay and cell apoptosis was
      analyzed by flow cytometry. We found that levels of SET, ABC transporters and
      PI3K/Akt pathway were elevated in MCF-7/PTX. Upregulation of SET in MCF-7/S cells
      expressed resistant to paclitaxel and decreased cell apoptosis. Moreover,
      overexpression of SET promoted the mRNA and protein level of ABC transporters and
      PI3K/Akt signal pathway in MCF-7/S cells. Conversely, decreased level of SET by
      COG112 not only significantly sensitized MCF-7/PTX cells to paclitaxel, but also
      enhanced paclitaxel-induced cell apoptosis. Additionally, the levels of the ABC
      transporters and PI3K/Akt signal pathway were also reduced in the COG112-treated
      MCF-7/PTX cells. The above results demonstrated that SET was associated with
      paclitaxel resistance in MCF-7/PTX cells.

PMID- 27718639
TI  - Perspective: 4beta-hydroxycholesterol as an emerging endogenous biomarker of
      hepatic CYP3A.
AB  - A key goal in the clinical development of a new molecular entity is to quickly
      identify whether it has the potential for drug-drug interactions. In particular,
      confirmation of in vitro data in the early stage of clinical development would
      facilitate the decision making and inform future clinical pharmacology study
      designs. Plasma 4beta-hydroxycholesterol (4beta-HC) is considered as an emerging
      endogenous biomarker for cytochrome P450 3A (CYP3A), one of the major drug
      metabolizing enzymes. Although there are increasing reports of the use of 4beta
      HC in academic- and industry-sponsored clinical studies, a thorough review,
      summary and consideration of the advantages and challenges of using 4beta-HC to
      evaluate changes in CYP3A activity has not been attempted. Herein, we review the
      biology of 4beta-HC, its response to treatment with CYP3A inducers, inhibitors
      and mixed inducer/inhibitors in healthy volunteers and patients, the association
      of 4beta-HC with other probes of CYP3A activity (e.g. midazolam, urinary cortisol
      ratios), and present predictive pharmacokinetic models. We provide
      recommendations for studying hepatic CYP3A activity in clinical pharmacology
      studies utilizing 4beta-HC at different stages of drug development.

PMID- 27718640
TI  - Targeted upper-limb Wii-based Movement Therapy also improves lower-limb muscle
      activation and functional movement in chronic stroke.
AB  - PURPOSE: Post-stroke hemiparesis may manifest as asymmetric gait, poor balance,
      and inefficient movement patterns. We investigated improvements in lower-limb
      muscle activation and function during Wii-based Movement Therapy (WMT), a
      rehabilitation program specifically targeting upper-limb motor-function. METHODS:
      Electromyography (EMG) was recorded bilaterally from tibialis anterior (TA) in 20
      stroke patients during a 14-day WMT program. EMG amplitude and burst duration
      were analyzed during stereotypical movement sequences of WMT activities.
      Functional movement ability was assessed pre- and post-therapy including 6-min
      walk test (6MWT), stair-climbing speed, and Wolf Motor Function Test timed-tasks.
      RESULTS: TA EMG burst duration during Wii-golf increased by 30% on the more
      affected side (p = 0.04) and decreased by 28% on the less-affected side. Patients
      who did not step during Wii-tennis had a 16% decrease in more-affected TA burst
      sum (p = 0.047) resulting in more symmetrical activation ratio at late-therapy,
      with the ratio changing from 3.24 +/- 2.25 to 0.99 +/- 0.11 (p = 0.047). Six
      minute walk and stair-climbing speed improved (p = 0.005 and 0.03, respectively),
      as did upper-limb movement (p <= 0.001). CONCLUSION: This study provides
      physiological evidence for lower-limb improvements with WMT. Different patterns
      of muscle activation changes were evident across the WMT activities. Despite the
      relatively good pre-therapy lower-limb function, muscle activation and symmetry
      improved significantly with upper-limb WMT. Implications for rehabilitation WMT
      is an upper-limb neurorehabilitation program that also improves lower-limb motor
      function. We report a shift towards more symmetrical muscle activation of
      tibialis anterior on the more- and less-affected sides that were reflected in
      increased distance walked during the 6MWT. The use of standing during therapy not
      only improves lower-limb function but also permits larger and more powerful upper
      limb movements. Targeted upper-limb rehabilitation can also significantly improve
      mobility and balance, whether dynamic or static, that should reduce the risk of
      falls post-stroke.

PMID- 27718641
TI  - Discovery and optimization of peptide macrocycles.
AB  - INTRODUCTION: Macrocyclic peptides are generally more resistant to proteolysis
      and often have higher potency than linear peptides and so they are excellent
      leads in drug design. Their study is significant because they offer potential as
      a new generation of drugs that are potent and specific, and thus might have fewer
      side effects than traditional small molecule drugs. Areas covered: This article
      covers macrocyclic drug leads based on nature-derived cyclic peptides as well as
      synthetic cyclic peptides and close derivatives. The natural peptides include
      cyclotides, sunflower-derived peptides, theta-defensins and orbitides.
      Technologies to make engineered cyclic peptides covered here include cyclization
      via amino acid linkers, CLIPS, templates, and stapled peptides. Expert opinion:
      Macrocyclic peptides are promising drug leads and several are in clinical trials.
      The authors believe they offer key advantages over traditional small molecule
      drugs, as well as some advantages over protein-based 'biologics' such as
      antibodies or growth factors. These include the ability to penetrate cells and
      attack intracellular targets such as protein-protein interactions as well as to
      hit extracellular targets. Some macrocyclic peptides such as cyclotides offer the
      potential for production in plants, thus reducing manufacture costs and
      potentially increasing opportunities for their distribution to developing
      countries at low cost.

PMID- 27718642
TI  - Assessing subacute mild traumatic brain injury with a portable virtual reality
      balance device.
AB  - PURPOSE: Balance impairment is a common sensorimotor symptom in mild traumatic
      brain injury (mTBI). We designed an affordable, portable virtual reality (VR)
      based balance screening device (Virtual Environment TBI Screen [VETS]), which
      will be validated relative to the Neurocom Sensory Organization Test (SOT) to
      determine if it can replace commonly used postural assessments. METHODS: This
      preliminary study examines healthy adults (n = 56) and adults with mTBI (n = 11).
      Participants performed six upright postural tasks on the VETS and the SOT.
      Analysis of variance was used to determine between-group differences. Pearson's
      correlations were used to establish construct validity. Known-groups approach was
      used to establish classification accuracy. RESULTS: The mTBI cohort performed
      significantly worse than the healthy cohort on the new device (p = 0.001). The
      new device has 91.0% accuracy and an ROC curve with a significant area-under-the
      curve (AUC = 0.865, p < 0.001). Conditions with dynamic visual stimulation were
      the most sensitive to health status. The SOT had an 84.8% accuracy and AUC =0.703
      (p = 0.034). CONCLUSIONS: The new VR-based device is a valid measure for
      detecting balance impairment following mTBI and can potentially replace more
      expensive and cumbersome equipment. Assessments that test visual-vestibular
      processing, such as VETS, increase sensitivity to mTBI-related balance deficits,
      which can be used to guide rehabilitation. Implications for rehabilitation
      Emerging technology using virtual reality can be economically integrated into the
      clinical setting for easy testing of postural control in neurologically impaired
      populations. Tailoring postural assessments to include tasks that rely on visual
      and vestibular integration will increase the accuracy of detecting balance
      impairment following mild traumatic brain injury.

PMID- 27718643
TI  - The effect of whole-body vibration therapy on bone metabolism, motor function,
      and anthropometric parameters in women with postmenopausal osteoporosis.
AB  - PURPOSE: To review the research literature on the effectiveness of whole-body
      vibration (WBV) therapy in women with postmenopausal osteoporosis. METHODS: A
      systematic review was conducted by two independent reviewers. Mean differences
      (MDs), standardized mean differences (SMDs), and 95% confidence intervals (CIs)
      were calculated, and heterogeneity was assessed with the I2 test. The Cochrane
      risk of bias tool was used to assess the methodological quality of the selected
      studies. RESULTS: Nine randomized controlled trials involving 625 patients met
      the inclusion criteria. No significant improvement was found in bone mineral
      density (BMD) (SMD = -0.06, 95%CI= -0.22-0.11, p = 0.50); bone turnover markers
      (MD = -0.25, 95%CI= -0.54-0.03, p = 0.08); anthropometric parameters, including
      muscle mass, fat mass, body mass index (BMI), and weight (SMD = 0.02, 95%CI= 
      0.16-0.21, p = 0.81); or maximal isotonic knee extensor strength (SMD = 0.16,
      95%CI= -0.63-0.95, p = 0.69). However, maximal isometric knee extensor strength
      improved (SMD = 0.71, 95%CI = 0.34-1.08, p = 0.0002). CONCLUSIONS: WBV is
      beneficial for enhancing maximal isometric knee extensor strength, but it has no
      overall treatment effect on BMD, bone turnover markers, anthropometric
      parameters, or maximal isotonic knee extensor strength in women with
      postmenopausal osteoporosis. Implication of rehabilitation Osteoporosis is the
      leading underlying cause of fractures in postmenopausal women, whole body
      vibration (WBV) has received much attention as a potential intervention for the
      management of osteoporosis in recent years. Whole body vibration is beneficial
      for enhancing maximal isometric knee extensor strength in women with
      postmenopausal osteoporosis. Whole body vibration has no overall treatment effect
      on bone mineral density, bone turnover markers, anthropometric parameters and
      maximal isotonic knee extensor strength in women with postmenopausal
      osteoporosis.

PMID- 27718644
TI  - Use of bacteriophage to prevent Pseudomonas aeruginosa contamination and fouling
      in Jet A aviation fuel.
AB  - In the present study, the use of bacteriophages to prevent growth and/or
      biofouling by Pseudomonas aeruginosa PAO1 was investigated in microcosms
      containing Jet A aviation fuel as the carbon source. Bacteriophages were found to
      be effective at preventing biofilm formation but did not always prevent
      planktonic growth in the microcosms. This result was at odds with experiments
      conducted in nutrient-rich medium, demonstrating the necessity to test
      antimicrobial and antifouling strategies under conditions as near as possible to
      the 'real world'. The success of the bacteriophages at preventing biofilm
      formation makes them potential candidates as antifouling agents for fuel systems.

PMID- 27718645
TI  - Stroke as a clinical emergency.
AB  - Figures from the National Audit Office ( 2005 ) reveal that stroke accounts for
      11 per cent of deaths in England and Wales each year, that up to 30 per cent of
      stroke patients die within a month of event, and that a quarter of people living
      to the age of 85 can expect to have a stroke.

PMID- 27718648
TI  - Job losses set to hit emergency departments.
AB  - Emergency nurses across the country have been warned to brace themselves as
      trusts cut jobs to offset actual or projected financial deficits.

PMID- 27718650
TI  - ?
AB  - End of the line: NHS Direct has announced that it plans to make 573 staff
      redundant and to close 12 call centres in a bid to ward off a financial crisis.
      An additional 216 posts will be lost through natural wastage and three executive
      level posts are also under threat. Although 376 new posts will be created, there
      will be a net loss of 413 posts. The proposals are out for consultation until
      August 16. For copies of the 'transformation consultation document', access
      www.nhsdirect.nhs.uk/articles/article.aspx?ArticleId=1858.

PMID- 27718649
TI  - All healthcare staff told: prepare for terrorism.
AB  - All healthcare staff, not only those working in emergency care services, have
      been urged to prepare for mass casualty incidents.

PMID- 27718651
TI  - Staff protection.
AB  - This month sees the launch of the first NHS Security Awareness Month to help
      ensure that no incident of abuse of, or assault on, staff is unreported.

PMID- 27718652
TI  - Internet clinic.
AB  - NHS Lothian has launched an internet physiotherapy clinic that offers instant
      advice on knee injuries.

PMID- 27718653
TI  - New appointment.
AB  - Former vice chair of the RCN Emergency Care Association Rob Sowney (pictured) has
      been appointed head of emergency care reform in Northern Ireland.

PMID- 27718654
TI  - Board's eye view.
AB  - Ever since I started my nursing career as a healthcare assistant in 1985, I have
      been intrigued by how nurses respond to death and the care of dying patients.

PMID- 27718655
TI  - Painful memories.
AB  - Many people attend A&E because they are in pain, and present either of their own
      volition or because their loved ones cannot cope with their suffering and have
      persuaded them to do so..

PMID- 27718656
TI  - Ambulance service trusts reconfigured.
AB  - Health minister Lord Warner has confirmed that the number of ambulance service
      trusts in England will be cut by more than a half, from 29 to 12, next month.

PMID- 27718657
TI  - Conference call.
AB  - Emergency nurses have been invited to attend a one-day conference in central
      London about harm minimisation in patients who self harm.

PMID- 27718658
TI  - [Analysis of hip fracture care in Hungary between 2004-2009].
AB  - INTRODUCTION: Proximal femoral fractures with severe outcome are most common in
      the increasing group of elderly patients. AIM: Based on the regular data gathered
      by the EuroHOPE research, the most important aspects and results of the treatment
      of proximal femoral fractures were studied. METHOD: Data of hospital admissions
      due to proximal femoral fractures were analyzed. RESULTS: There was a slight
      increase in the number of hospitalized patients between 2004 and 2009 in Hungary.
      88% of the patients received operative treatment, 41% suffered femoral neck
      fractures. Mortality rates did not change significantly in the analyzed period.
      Standardized annual mortality rates for patients who had suffered a femoral neck
      fracture were 28% when prosthesis was implanted; this result was somewhat more
      favorable than in case of other surgical procedures. Annual mortality rates were
      higher in the peritrochanteric fracture group where intramedullary nailing was
      performed (36%). The ratio of operated patients did not differ significantly from
      international results. Mortality rates in Hungary were significantly less
      favorable. 30 day standardized mortality rate was 13.6% in 2008, twice as high as
      the rate in Finland, The Netherlands, Norway, Scotland and Sweden. The 40%
      mortality rate calculated for 365 days was significantly higher than
      international results. CONCLUSION: To define the measures needed to improve
      results, systematic analysis of both in-hospital treatment protocols, and follow
      up treatment is necessary. Orv. Hetil., 2016, 157(41), 1642-1648.

PMID- 27718659
TI  - [Methods of the EuroHOPE research program].
AB  - The European Health Care Outcomes, Performance and Efficiency research was
      financed by the European Union between 2010 and 2013. In this program a new
      methodology was developed which made the analysis of regularly collected data and
      international benchmarking of the healthcare results of 5 socially and
      economically critical diagnosis group between the 7 participant countries
      possible. This paper presents the most important areas of the development, such
      as (1) the principles of the methodology, (2) the definition of available
      databases, code systems, (3) the events to be analysed, (4) the general rules of
      analyses and indicator development, (5) the exact methodology of data collection,
      processing, and analysis, (6) the methods of risk adjustment, (7) and the
      development of the standardised database. The databases which include all
      information of all patients and healthcare activities serve as perfect
      inexhaustible data sources for decision makers, healthcare personnel, and
      researchers. The indicator results of this program serve as starting point for
      further root cause analysis and development measures based on the results of the
      abovementioned analyses. Orv. Hetil., 2016, 157(41), 1619-1625.

PMID- 27718660
TI  - [Results of stroke care in Hungary in the frame of international comparison].
AB  - INTRODUCTION: The EuroHOPE FP7 project analysed the effectiveness and efficiency
      of stroke care between 2010 and 2014. AIM: The study introduces Hungarian data in
      comparison with international results and explores the causes of differences.
      METHOD: The analysis was performed on data available from regular data collection
      in Finland, The Netherlands, Hungary, Italy, Scotland, and Sweden, with
      standardized indicators. Hungarian data was analysed between 2005 and 2009, and
      the international benchmarking in 2008, with multivariate logistic regression
      analysis for risk adjustment. RESULTS: Stroke incidence in Hungary was the double
      of the Italian or Finnish results (43.3/10,000 inhabitants), while comorbidities
      did not differ among countries. In Hungary, 19.9% of patients purchased anti
      coagulants, one-third of the rate in Finland. One-year mortality in Hungary was
      30%, the worst among the countries. Possible causes are inadequate prevention,
      more severe status of patients, and deficiencies of hospital care and
      rehabilitation. CONCLUSION: Causal analysis of these results and corrective
      measurements are recommended. Orv. Hetil., 2016, 157(41), 1635-1641.

PMID- 27718662
TI  - [Editor's Commentary].

PMID- 27718661
TI  - [Mortality rates of very low birth weight and very low gestational age newborns
      in Hungary. The EuroHOPE study].
AB  - INTRODUCTION: Care provision for very low birth weight and very low gestational
      age newborns requires high level clinical preparedness. Appropriate care and care
      management reduce mortality. AIM: To present Hungarian and international outcomes
      and local regional differences characterizing neonatal care in 2006-2008, based
      on the results of the EuroHOPE study. METHOD: Hungarian data were created by
      linking the obstetrics registry with the financing database of the Health
      Insurance Fund. Resulting from peculiarities of these databases and clinically
      justified exclusions, 3562 newborns were included. RESULTS: Hungarian risk
      adjusted 365-day mortality rate was significantly higher than in most of the
      studied countries. Incidence of diseases correlated with higher mortality risk
      was highest in Hungary. Mortality in two Hungarian counties was worse than
      expected based on modelling, while it was better in one county. CONCLUSIONS:
      Systematic factors might cause these results. Relatively low usage rate of
      steroid prophylaxis in Hungary might contribute to unfavorable mortality figures.
      A common unique identifier would help database linkage. Orv. Hetil., 2016,
      157(41), 1649-1656.

PMID- 27718664
TI  - Eye emergencies.
AB  - This study compares the accuracy and reliability of emergency nurse practitioners
      (ENPs) with those of junior A&E doctors, namely senior house officers (SHOs),
      when assessing eye emergencies.

PMID- 27718663
TI  - [Main characteristics of the care of acute myocardial infarction in Hungary
      between 2005-2009, based on the results of the EuroHOPE research].
AB  - INTRODUCTION: The EuroHOPE research developed the standardised methodology of the
      analysis of the healthcare process. AIM: The aims of the authors were to analyze
      the care of acute myocardial infarction in Hungary and to compare the results to
      those of the partner countries. METHOD: The authors analyzed the application of
      early and late invasive interventions, medication purchase, and mortality. The
      results were compared to Finnish, Norwegian, Italian, Scottish and Swedish data.
      RESULTS: By the end of the observed period, approximately half of the patients
      received early treatment, which is an internationally acceptable result. Purchase
      of statins, angiotensin converting enzyme inhibitors, and angiotensin receptor
      blockers was around 90%, but the application of beta-blockers has decreased for
      unknown reason. The mortality rate has improved, but it was still significantly
      worse than that in the partnering countries. One year mortality in the early
      intervention group was 1.5 times higher, and in the late intervention group was 2
      times higher than the second worst results. CONCLUSIONS: The causal analysis
      concerning the professional activities, operational practices, and the role of
      the patients in the observed period is highly recommended. For more detailed
      analysis it is necessary to follow the trends and to separate the diagnoses of ST
      elevation and non-ST-elevation acute myocardial infarction. Orv. Hetil., 2016,
      157(41), 1626-1634.

PMID- 27718665
TI  - Your letters.
AB  - As a past participant of the King's Fund leadership programme, I realise that
      there are real benefits in equipping nurses with the necessary skills to
      modernise health care delivery by influencing policy, breaking down professional
      barriers and facilitating others to think differently about how care is
      delivered.

PMID- 27718666
TI  - Pre-hospital care.
AB  - The ambulance service has been seen traditionally as an organisation of
      transportation. Increased demands on the NHS however have led to prehospital
      emergency services becoming an important part of holistic care provision.

PMID- 27718668
TI  - Waste not, want not.
AB  - The memory of summer is dwindling formany of us, I should think, but some will
      recall working in temperatures of more than 28 degrees C during this year's hot
      weather spells.

PMID- 27718667
TI  - RCN congress 2006.
AB  - Emergency nurses have been invited to notify the RCN Emergency Care Association
      of issues they want raised for debate at RCN congress.

PMID- 27718669
TI  - Career move.
AB  - Judith Morgan, RCN Emergency Care Association newsletter editor, is moving job
      next month.

PMID- 27718671
TI  - Hygiene drive.
AB  - Emergency nurses have been urged to take department hygiene seriousl as part of
      the national drive to reduce healthcare acquired infections.

PMID- 27718670
TI  - EN support for public-private co-operation.
AB  - Leading emergency nurse Brian Boag (pictured) spoke out at Labour's conference
      last month in support of the government drive towards greater co-operation
      between the public and private sectors.

PMID- 27718672
TI  - Conference call.
AB  - The Nursing and Midwifery Council consultation on advanced pract ice and managing
      failing students are among the topics to be tackled this month at a meeting of
      the Network of Emergency Learning Facilitators (NELF).

PMID- 27718673
TI  - Emergency nurses to pilot skill mix tool.
AB  - Delegates at the annual RCN Emergency Care Association conference next month are
      to be invited to test run the latest proposals for establishing departmental
      skill mix.

PMID- 27718674
TI  - Health promotion.
AB  - The premise of this study is that, while much has been written about health
      promotion in relation to community nurses, little has been written about the
      subject in relation to A&E nurses.

PMID- 27718675
TI  - Stroke awareness.
AB  - The Stroke Association is launching an 18-month campaign this month to raise
      awareness over the need to treat stroke as an emergency.

PMID- 27718676
TI  - ?
AB  - Falling into place: the Health and Safety Executive (HSE) last month launched its
      Watch Your Step campaign to highlight how falling or tripping over at work can
      lead to serious injuries. Figures presented by the HSE suggest that falls
      accounted for more than 42,000 workplace injuries last year in the UK, including
      almost 3,000 serious injuries in the health services sector alone. Health and
      Safety Executive acting chief executive Justin McCracken said: 'Slips and trips
      are often seen as a bit of a joke. This is not a laughing matter for either the
      injured party or the business, particularly when absenteeism, insurance, wage and
      civil liability costs are taken into consideration.'

PMID- 27718677
TI  - ?
AB  - Heart of the matter: A&E based nurse Jane Arnold has won a Leading Practice
      through Research award from The Health Foundation to develop a patient leaflet on
      the symptomsand diagnosis of acute chest pain. Ms Arnold, a chest pain assessment
      nurse at the Northern General Hospital, Sheffield, said: 'Working full-time
      leaves limited scope for professional development outside the clinical field.
      This award provides me with the opportunity to reflect on my practice, gain new
      research skills and add to the leadership and management skills that I have
      already acquired. My project will help determine whether provision of information
      sheets should be standard practice for patients with acute chest pain in an
      emergency setting.' For further details of the charity's award scheme, access
      www.health.org.uk.

PMID- 27718678
TI  - ?
AB  - New direction: a half of ambulance journeys to hospital could be unnecessary
      because many patients can be treated better elsewhere, according to an NHS
      Confederation report entitled NHS Ambulance Services: More than just patient
      transport. The report cites the role of emergency care practitioners and
      'smarter' patient assessment as two of the reasons why patients are treated
      increasingly at incident scenes or in the community. For copies of the report,
      published this month, access www.nhsconfed.org/docs/amb_report.pdf.

PMID- 27718679
TI  - Emergency care strategy launched.
AB  - The Welsh Assembly Government (WAG) published its proposals this month for a
      national strategy for developing emergency care.

PMID- 27718681
TI  - Help for PTSD.
AB  - An NHS leaflet has after been published to highlight the symptoms of post
      traumatic stress disorder (PTSD) the London terrorist bombings a year ago this
      month. The publication contains advice on why people should seek professional
      help, how they can know that they need help, how they may be screened for PTSD or
      other psychological conditions, and what treatment is available.

PMID- 27718680
TI  - Warning over EN professional development.
AB  - Ministers have been warned that emergency services will suffer unless staff are
      given more opportunity for continuing professional development.

PMID- 27718682
TI  - Birthday honour.
AB  - National clinical director for patient experience in A&E at the Department of
      Health Jonathan Asbridge (pictured) heads the list of senior nurses in the
      Queen's birthday honours this year by becoming a knight. Sir Jonathan is also
      president of the Nursing and Midwifery Council.

PMID- 27718683
TI  - ?
AB  - Record busting: the emergency care of patients with heart attack in England and
      Wales is the best in the world, according to the latest Myocardial Infarction
      National Audit Project (MINAP) report. The report shows that, in England, the 30
      minute door-to-needle target for thrombolysis was met in 83 per cent of cases in
      2005/06, compared to just 44 per cent in early 2001. In Wales, the target was met
      in 74 per cent of cases, up from 65 per cent in 2003/04. For copies of the
      report, published last month, access www.rcplondon.ac.uk/pubs/books/minap06.

PMID- 27718684
TI  - Tetanus shortage.
AB  - Supplies of tetanus immuno- globulin (TIG) may not be restored before next month,
      according to Department of Health director of immunisation policy, monitoring and
      surveillance David Salisbury.

PMID- 27718685
TI  - Organ donation.
AB  - This article shares the work of the Organ Donation Breakthrough Collaborative
      (ODBC) in the United States.

PMID- 27718686
TI  - Conference call.
AB  - The RCN emergency care forum of Northern Ireland is holding this year's annual
      conference on September 27 at the RCN Northern Ireland headquarters, Belfast.
      Abstracts need to be submitted by July 17. For more details, email Roisin Devlin
      at rosydevlin@yahoo.co.uk.

PMID- 27718688
TI  - Prize winner.
AB  - Emergency department staff nurse Alexandra Holden has won a digital radio worth
      L100 after taking part in the latest Emergency Nurse reader survey. Until
      recently, Ms Holden worked at Russells Hall Hospital, part of The Dudley Group of
      Hospitals NHS Trust, but now works at several emergency departments as an agency
      nurse.

PMID- 27718689
TI  - Put yourself in print.
AB  - It's the time of year for academic marking once again and, if you have written a
      coursework assignment, you can breathe a sigh of relief now that it has been
      submitted.

PMID- 27718690
TI  - your letters.
AB  - The Department of Health is undertaking a project to review NHS implementation of
      the guidance contained in its document Safeguarding Children in Whom Illness is
      Fabricated or Induced ( DH 2002 ).

PMID- 27718691
TI  - Emergency care nurse training.
AB  - James Bird presents an interesting case for specialised emergency care during
      student nurse training in the June issue of Emergency Nurse. However the answer
      to his opening question, 'Is general nursing coming to an end?', is surely 'No';
      it already has.

PMID- 27718692
TI  - Minor injuries in accident & emergency Minor injuries in accident & emergency
      Ffion Davies and Barbara Stahl OCB Media Ltd L29.99 1-904039-12-X 190403912X
      [Formula: see text].
AB  - From the makers of the Spotting the Sick Child DVD ROM comes another useful
      educational resource for emergency clinicians.

PMID- 27718693
TI  - Categorising errors.
AB  - The aim of this American study was to test the reliability and validity of the
      Eindhoven Classifiation Model for categorising errors in emergency department
      settings.

PMID- 27718694
TI  - Nasal injuries.
AB  - Nasal injuries are common presentations in emergency departments and those who
      present with them often simply require reassurance. If patients require
      intervention however, they are generally referred to otolaryngology departments,
      or for plastic or maxillofacial surgery.

PMID- 27718696
TI  - Can we afford the NHS?
AB  - The structure, development and reorganisation of the NHS have been under close
      and almost constant scrutiny since it was devised nearly 60 years ago to provide
      free health care to the UK population. Over this time, it has been the subject of
      many initiatives to reform its management of public health, care delivery and
      provision of services.

PMID- 27718697
TI  - Tissue donation.
AB  - The donation of tissues is often a more realistic option in emergency care
      settings than that of organs, which need perfusion before harvesting, yet many
      professionals know less about tissue than organ donation.

PMID- 27718700
TI  - Organ transplant.
AB  - Nurses in emergency care settings are often asked for information about organ or
      tissue transplants and called on to clarify the circumstances in which people can
      or cannot donate.

PMID- 27718698
TI  - Body piercing jewelry removal kit S De Boer Amundson T Body piercing jewelry
      removal kit Med-Pierce Format: Two DVDs, Tattoos, Tongues, Teenagers and Trauma
      and Step by Step Body Piercing Removal, and a Step by Step Guide handbook, pliers
      and jewellery samples $299.95 [Formula: see text].
AB  - This multi-media resource is intended for a wide range of healthcare
      professionals, from emergency department to prison staff, to help familiarise
      them with body piercings and how they affect procedures such as diagnostic
      imaging, defibrillation and surgery.

PMID- 27718701
TI  - Cardiac care: an introduction for healthcare professionals D Barrett Cardiac
      care: an introduction for healthcare professionals M Gretton , T Quinn Wiley and
      Sons L24.99 0 470 01983 2 0 470 01983 2 [Formula: see text].
AB  - As the title suggests, this excellent book provides an introduction to cardiac
      care to all healthcare professionals who care for cardiac patients.

PMID- 27718703
TI  - Blood transfusion.
AB  - The UK blood transfusion and tissue transplantation services site meanwhile, at
      www.transfusionguidelines.org/index.asp , provides clinical information,
      professional guidelines and examples of best practice, as well as information on
      donor selection.

PMID- 27718704
TI  - Firework safety.
AB  - At this time of year, many different people celebrate important days in their
      calendars, from Diwali to Guy Fawkes Night, with firework displays.

PMID- 27718705
TI  - ?
AB  - The citation for noel's first victoria cross: 'During an attack, he tended the
      wounded in the open all day, under heavy fire, frequently in view of the enemy.
      During the ensuing night, he searched for wounded on the ground in front of the
      enemy's lines for four hours.

PMID- 27718706
TI  - New federation.
AB  - Emergency care staff have been invited to join a new group of nurses and doctors,
      the and doctors, the Welsh Emergency Department Federation (WEDFed).

PMID- 27718707
TI  - Protecting the public.
AB  - The Nursing and Midwifery Council (NMC) was established in 2002 by parliament
      with a clear remit to protect the public. Through its standards, codes, rules and
      guidance, the council sets out a path to enable practitioners to develop
      professionally but also to remain safe and effective. Many emergency nurses will
      have voted in the NMC elections earlier this year, and the first elected council
      began work on July 31.

PMID- 27718708
TI  - ECA election win.
AB  - Rabina Tindale has been elected onto the RCN Emergency Care Association (ECA)
      steering committee.

PMID- 27718709
TI  - Health promotion.
AB  - For those who want to evaluate the evidence of efficacy of different health
      promotion and education initiatives, the Welsh health evidence site, at
      hebw.cf.ac.uk/index.html , could be ideal.

PMID- 27718710
TI  - Aggressive therapy urged for sepsis.
AB  - Emergency nurses can save lives and help their trusts save money by helping to
      introduce early aggressive therapy for severe sepsis, research suggests.

PMID- 27718712
TI  - Child care seats.
AB  - On the subject of child restraint in vehicles, another recent change in
      legislation has created a complex set of circumstances in which exemption from
      the rules can be allowed.

PMID- 27718711
TI  - ?
AB  - In hot water: the RCN Emergency Care Association (ECA) is backing MP Mary
      Creagh's campaign to have thermostatic valves fitted in all new and refurbished
      homes to prevent scalding. The valves set bath tap water temperature to a maximum
      of 48 degrees C. The ECA steering committee has submitted the subject of Ms
      Creagh's Hot Water Burns Like Fire campaign as a matter for discussion at RCN
      congress, next April.

PMID- 27718713
TI  - Conference call.
AB  - The Health protection Agency is hosting a conference entitled The London
      Bombings: Health protection lessons from London and other international
      incidents. The conference is on November 30 at the Royal College of Surgeons,
      London.

PMID- 27718715
TI  - Your letters.
AB  - The innovative work of the emergency care collaboration in Wales has set a pace
      for change in emergency care service delivery.

PMID- 27718714
TI  - Preventing accidents.
AB  - The Royal Society for the Prevention of Accidents also hosts a comprehensive
      site, at www.rospa.com/ , for emergency department staff developing accident
      prevention resources.

PMID- 27718719
TI  - End of the line for mobile phones?
AB  - Mobile phones have become so commonplace that it is difficult to go anywhere
      these days without seeing or hearing them.

PMID- 27718720
TI  - Web scan.
AB  - This selection of sites is intended for emerg ency nurses who treat patients with
      injuries to the eye, or to the shoulder and elbow.

PMID- 27718721
TI  - At cross purposes.
AB  - I would like to point out a discrepancy in the April issue of Emergency Nurse
      relating to the article, Shoulder dislocation: reduction without sedation in the
      emergency department, on pages 24-28.

PMID- 27718722
TI  - Board's eye view.
AB  - An article in last month's issue of Emergency Nurse described a research project
      into the experiences of Australian A&E nurses when dealing with patients with
      mental health problems.

PMID- 27718723
TI  - Sudden infant death syndrome Dawne J Gurbutt Sudden infant death syndrome
      Radcliffe Publishing 128 L17.95 13 978-1846190384 139781846190384 [Formula: see
      text].
AB  - This book offers an account of a research project, undertaken by a nurse lecturer
      and health visitor, into the experiences of mothers who had lost babies because
      of sudden infant death syndrome (SIDS).

PMID- 27718725
TI  - Electronic library.
AB  - The RCN has launched an enhanced electronic library service for members. The
      service, at www.rcn.org.uk/ library from this month, aims to provide quicker and
      easier access to full text information.

PMID- 27718724
TI  - ?
AB  - Child's play: emergency staff nurse Mick Downs from Colchester General Hospital,
      Essex, helped local children from Ardleigh Pre-School celebrate Red Cross Appeal
      Week last month by telling them about his job. He also showed the children how to
      make a sling and told them when it's appropriate to phone 999. Mr Downs has
      worked in the is a divisional officer for adults and also helps cadets.

PMID- 27718726
TI  - Forced marriage.
AB  - Guidelines to help A&E staff and other healthcare professionals who suspect cases
      of forced marriage were launched this month by the government. The guidelines
      provide practical advice on how to recognise the warning signs, and what to do if
      patients disclose that they have been, or are about to be, forced to marry. The
      guidelines, Dealing with Cases of Forced Marriage, are available at
      www.fco.gov.uk/forcedmarriage.

PMID- 27718727
TI  - ?
AB  - Stub it out: banning smoking while driving would help reduce pressure on nurses
      working in emergency care, according to experts. From July 1, it is unlawful to
      smoke in enclosed public places across England. The Local Authority Road Safety
      Officers Association has called on the government to introduce a blanket ban on
      smoking at the wheel as well. Mental health nurse David Harding-Price agrees: 'If
      there is a multiple pile up because someone has dropped a cigarette butt and is
      not concentrating, it affects nurses right across the board. Those in A&E and
      theatre have to deal with the casualties and mental health nurses may have to
      deal with bereaved relatives'.

PMID- 27718728
TI  - Shock resignations from Emergency Care Association.
AB  - The RCN is discussing the future of its Emergency Care Association (ECA) this
      month after the surprise resignation of three committee members including the
      chair.

PMID- 27718729
TI  - Call to 'shelve' walk-in centre plans.
AB  - Emergency care experts have called on politicians to shelve proposals for the
      introduction of walk-in centres in Wales.

PMID- 27718731
TI  - Board's eye view.
AB  - Discrimination in the workplace is wrong and extremely unpalatable, but the type
      of discrimination that I've sometimes felt as a man in the nursing profession
      pales into insignificance when compared to racial discrimination or prejudice.

PMID- 27718730
TI  - Social adaptation following intestinal stoma formation in people living at home:
      a longitudinal phenomenological study.
AB  - PURPOSE: Intestinal stoma formation profoundly changes the relationship between a
      person and their social world. The aim of this study was to understand the
      experience of living with a new stoma; this paper explores the theme "disrupted
      social world," highlighting how stoma-forming surgery impacts on individuals'
      abilities to participate and interact socially over time. METHOD: A longitudinal
      phenomenological approach. Twelve participants with a new stoma were recruited
      using purposeful sampling. Data were collected at three, nine and 15 months
      following surgery through in-depth, unstructured interviews and analysed using a
      bespoke iterative framework. RESULTS: Three categories were identified:
      participation in the social environment; interpersonal relationships: changes and
      challenges; and setting and achieving goals. CONCLUSIONS: Stoma-forming surgery
      changes the ways people relate to their social environment and connect with
      others, creating self-consciousness and impeding social confidence and autonomy.
      Understanding the social implications of stoma-forming surgery can help
      clinicians to provide responsive and appropriate support to facilitate social
      rehabilitation. Implications for Rehabilitation Assisting people with a stoma to
      develop competent stoma self-care skills will promote social adaptation and self
      acceptance. Clinicians should promote access to others with a stoma, an important
      source of support for many people adjusting to a new stoma. Graded exposure to
      social participation can engender feelings of control and confidence for people
      with a stoma. Clinicians can help individuals with a stoma to set realistic goals
      for their recovery, while encouraging a range of positive coping strategies.

PMID- 27718732
TI  - Smoking research.
AB  - Research has revealed that there has been a 17 per cent fall in hospital
      admissions for heart attack in the first year after the smoking ban in Scotland
      came into force.

PMID- 27718733
TI  - Aromatherapy.
AB  - With the introduction of extended roles, the pressures of meeting government
      targets and the contin ual rise in the number of patients seen in emergency
      departments (EDs), emergency nurses have been experiencing increasing levels of
      occupational stress.

PMID- 27718734
TI  - Consent to act.
AB  - The last clauses of the Mental Capacity Act 2005 are finally implemented this
      month. As a result, enduring powers of attorney have been replaced by lasting
      powers of attorney to give people with mental health problems greater control
      over their lives and more choice about their futures.

PMID- 27718735
TI  - Emergency nurses 'not add-on' in care strategy design.
AB  - The government has been called on to involve emergency nurses more in the design
      and roll out of its new urgent and emergency care strategy.

PMID- 27718736
TI  - NICE updates guideline on head injuries.
AB  - The National Institute for Health and Clinical Excellence (NICE) has updated its
      guideline on the early care of adults and children with head injuries.

PMID- 27718738
TI  - Self harm.
AB  - Reports suggest that some emergency nurse practitioners demonstrate'negative
      attitudes' to patients presenting with self harm.

PMID- 27718737
TI  - Chest pain: Advanced assessment and management skills Chest Pain: Advanced
      assessment and management skills Jenny Tagney and John Albarran Blackwell
      Publishing 2007 264 L27.99 978 1 4051 4422 3 140514422X [Formula: see text].
AB  - As this textbook highlights, chest pain is one of the most common reasons why
      people seek healthcare advice in Europe and North America. It results in an
      estimated 634,000 primary care consultations and 700,000 emergency department
      attendances annually in England and Wales.

PMID- 27718739
TI  - ?
AB  - Yellow alert: the Children's Liver Disease Foundation has launched a campaign to
      help emergency nurses and other healthcare professionals recognise and take
      action on neonatal liver disease. Backed by the RCN, the Yellow Alert campaign
      highlights the key signs and symptoms of the potentially fatal condition:
      jaundice of the skin beyond two weeks in term babies and three weeks in preterm
      babies, yellow urine, pale stools, and yellowing of the sclera of the eyes, a key
      tool in detecting jaundice in all ethnic and racial groups. Foundation chief
      executive Catherine Arkley said: 'The signs of neonatal liver disease are simple
      and visual but they are often overlooked, particularly as the baby can look and
      feed well.' For free campaign packs, email yellowalert@childliverdisease.org or
      call 0121 212 3839.

PMID- 27718740
TI  - Improving services for children.
AB  - The guest editorial by Tanya Collinsand Mark Dawes in September's issue of
      Emergency Nurse made interesting reading.

PMID- 27718741
TI  - Answers to september's self assessment questionnaire.
AB  - Here are the answers to Lorna McInulty's self assessment questionnaire (SAQ) on
      gout, which was published in the September issue of Emergency Nurse.

PMID- 27718742
TI  - Clarification.
AB  - In the article entitled Anaphylaxis: recognition, treatment and education,
      published in the May issue of Emergency Nurse, Fig. 1, on page 27, should read
      'If there is a history of severe allergic type reaction with respiratory
      difficulty or hypotension' not 'hypertension'.

PMID- 27718743
TI  - Foreword.

PMID- 27718744
TI  - Monitoring safety and use of old and new treatment options for type 2 diabetic
      patients: a two-year (2013-2016) analysis.
AB  - OBJECTIVE: To compare patients' and physicians' perceptions regarding
      effectiveness and tolerability of non-insulin hypoglycemic drugs in a cohort of
      type 2 diabetic patients; to verify whether a possible tridimensional link
      between effectiveness, tolerability, and adherence affects long-term therapeutic
      outcomes. METHODS: A two-year observational study was performed in 1389 Type 2
      diabetic patients by involving general practitioner clinics and Diabetes Centers.
      A decimal scale and the Morisky questionnaire were used, respectively, to assess
      effectiveness and tolerability perceptions, and medication adherence. RESULTS:
      Physicians perceived therapy as more efficacious compared to their patients:
      perceived effectiveness was steady for physicians during the study whereas
      patients' perception not significantly decreased (mean score from >8 to 7.84 +/-
      1.69). Physicians assigned higher tolerability scores compared to patients but
      only at the beginning of the study; interestingly, physicians' tolerability
      perception was poorer than patients' perception at last follow-up (mean score =
      7.57 +/- 1.40 vs. 7.88 +/- 1.84). Favorable (score >7) patients' perceptions
      about treatment effectiveness and tolerability were associated with higher
      adherence. Patients showed medium adherence across the study. CONCLUSIONS: A
      mutual relationship between clinical effectiveness, adverse drug reactions, and
      adherence has been established, significantly impacting the clinical management
      of diabetic patients. A careful monitoring of this link by clinicians appears
      therefore necessary.

PMID- 27718745
TI  - Pharmacogenetics of neurological and psychiatric diseases at older age: has the
      time come?
AB  - INTRODUCTION: In recent years, a number of pharmacological approaches for
      treating neuropsychiatric conditions at older age have proven to be inadequate.
      The resulting increased prevalence of therapeutic failures (TF) and a worsening
      of clinical symptoms often linked to adverse reactions (ADRs), are perhaps among
      the major causes of the increasing rate of hospitalizations and
      institutionalizations observed in these patients. Areas covered: This review
      underlines the importance of pharmacogenetic data to fingerprint the
      pharmacological treatment of neuropsychiatric late-life conditions throughout the
      analysis of metabolizing enzymes and transporters of psychotropic drugs, mainly
      those of the cytochrome P450 (CYP) family. Pharmacodynamic response measures as
      treatment effects mediated through targets (i.e., receptors in the brain) may
      also contribute to this image. Expert opinion: CYP genetics is the basis of a
      continuum on which environmental and physiological factors act, modeling the
      phenotype observed in clinical practice with advancing age. Furthermore, other
      specific polymorphic genes influence drug response through differential effects
      of their functional genetic variants. The known genotypes associated with an
      altered metabolizer status and drug transporters may help clinical decision
      making to avoid concomitant treatments, reduce therapeutic attempts and increase
      drug safety in neuropsychiatric conditions in older age, after controlling for
      other clinical variables.

PMID- 27718746
TI  - Incidence and implications of chemotherapy related hand-foot syndrome.
AB  - INTRODUCTION: Hand-foot syndrome (HFS) is a well-established cutaneous adverse
      event of certain chemotherapeutic agents, mainly capecitabine, continuously
      infused 5-fluorouracil, docetaxel and pegylated liposomal doxorubicin. Erythema,
      dysesthesia, pain, cracking and desquamation located on palms and soles are the
      most characteristic manifestations. Although HFS is a reversible and non-life
      threatening clinical condition, it can often affect patient's quality of life
      significantly, hence necessitating therapeutic modifications or even treatment
      discontinuation. Areas covered: This is review article on current data regarding
      the clinical characteristics, grading and management of HFS. Special focus has
      been given to recent literature studying novel therapeutic strategies. Expert
      opinion: Early recognition, patient education and supportive measures are
      considered as the key elements in the management of HFS. Up to date, treatment
      interruption and dose intensity reduction are the mainstay of HFS management.
      Many topical formulations and systemic treatment regimens have been proposed,
      with COX-2 inhibitors being the most promising agents. Nevertheless, large
      prospective randomized controlled trials are needed in order to agree on solid,
      evidence-based treatment algorithms.

PMID- 27718747
TI  - Anti-CD20 monoclonal antibodies in multiple sclerosis.
AB  - INTRODUCTION: The therapeutic utility of the anti-CD20 monoclonal antibodies
      (mAbs) is currently being evaluated in multiple sclerosis (MS) in line with the
      better understanding of the role of B lymphocytes in MS pathogenesis. Area
      covered: We conducted a literature search using Medline/Pub Med database of basic
      research and available controlled trials about anti-CD20 mAbs in MS.
      Additionally, ongoing studies were identified in the ClinicalTrials.gov database.
      B cells exert multiple inflammatory and regulatory functions playing an important
      role in MS pathogenesis as is demonstrated by the production of autoantibodies,
      infiltration of B cells in MS lesions and the formation of ectopic B cell
      follicle-like structures in meninges, among others. B-cell depletion by anti-CD20
      mAbs has been shown to have an impact on these pathogenic mechanisms. The
      efficacy of three of them, rituximab, ocrelizumab and ofatumumab in MS has been
      confirmed by placebo-controlled clinical trials demonstrating a significant
      reduction of the annualized relapsing rate (ARR), new gadolinium-enhancing (GdE)
      and T2 lesions. There have been no significant safety problems so far but the
      overall benefit to risk profile is still to be determined. Expert commentary:
      After recent good results of these agents in MS therapy, questions related to
      maintenance therapy, markers of response and control of B cells values remain
      unanswered.

PMID- 27718748
TI  - Utility of the adverse outcome pathway concept in drug development.

PMID- 27718749
TI  - Palliative care in progressive multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis (MS) is a progressive disease of the central
      nervous system with unknown etiology. It could be associated with severe
      disability and losses of physical, psychological and social role functioning over
      time. People with MS share experiences in common with people affected by diseases
      with a shorter and clearer terminal phase. Therefore, it is appropriate to offer
      a palliative care approach to people with severe MS and their caregivers. Areas
      covered: Benefits for severe MS patients and their caregivers were shown when
      palliative care was included in their care. However, many neurologists show no
      interest toward palliative care services for people with severe MS.
      Misunderstandings about the services of palliative care are still prevalent.
      Expert commentary: When all results are considered, they show that palliative
      care for severe MS patients may be beneficial. The five-year view will discuss
      the barriers of palliative care inclusion for people with severe MS.

PMID- 27718750
TI  - Platelet proteomics applied to the search for novel antiplatelet therapeutic
      targets.
AB  - INTRODUCTION: Unwanted platelet activation is associated with numerous diseases,
      mainly thrombosis-related. In this context, proteomics has emerged as a novel
      tool with potential for drug target discovery and to scrutinize the effects of
      antiplatelet drugs. Areas covered: The present review presents the main findings
      of platelet proteomic studies to date in the context of drug target discovery and
      perspectives for the future ahead. It includes data and evidences obtained from
      literature searches on PubMed as well as commentaries derived from the authors'
      experience and opinions. Expert commentary: Platelet proteomics applied to drug
      target discovery is a young field. Recent studies have shown promising data,
      especially in the context of coronary artery disease. However, challenges remain
      such as establishing definitive guidelines for blood collection and platelet
      isolation, essential to guarantee data reproducibility. Recent advances in
      quantitative platelet proteomics should lead to novel studies with higher
      clinical impact in the near future.

PMID- 27718751
TI  - Tedizolid in skin and skin structure infections: brave new world?

PMID- 27718752
TI  - Bronchodilators in cystic fibrosis: a critical analysis.
AB  - INTRODUCTION: Cystic fibrosis airways disease is characterized by chronic
      inflammation and infection resulting in bronchiectasis. Published guidelines
      recommend medications for use by CF patients to maintain lung health. There are
      conflicting recommendations regarding inhaled bronchodilators. This is primarily
      because of the interpretation of the available evidence, which suffers from
      studies using small numbers of subjects, varying doses and durations of
      treatment, and modest effects on clinically relevant endpoints. Areas covered:
      Herein we review the available evidence demonstrating the challenge in
      determining whether bronchodilators have benefit for patients. We examine the
      potential indications and the current guidance from clinical studies. We
      highlight the outstanding questions examining bronchodilator use in CF. Expert
      commentary: The use of bronchodilators in CF remains commonplace despite the lack
      of solid evidence. Further studies should define key endpoints to determine a
      role for bronchodilators in light of a substantial treatment burden endured by
      people with CF.

PMID- 27718753
TI  - Proteomics approach to identify biomarkers for upper gastrointestinal cancer.
AB  - INTRODUCTION: The prognosis for patients with upper gastrointestinal cancers
      remains dismal despite the development of multimodality therapies that
      incorporate surgery, chemotherapy, and radiotherapy. Early diagnosis and
      personalized treatment should lead to better prognosis. Given the advances in
      proteomic technologies over the past decades, proteomics promises to be the most
      effective technique to identify novel diagnostics and therapeutic targets. Areas
      covered: For this review, keywords were searched in combination with "proteomics"
      and "gastric cancer" or "esophageal cancer" in PubMed. Studies that evaluated
      proteomics associated with upper gastrointestinal cancer were identified through
      reading, with several studies quoted at second hand. We summarize the proteomics
      involved in upper gastrointestinal cancer and discuss potential biomarkers and
      therapeutic targets. Expert commentary: In particular, the development of mass
      spectrometry has enabled detection of multiple proteins and peptides in more
      biological samples over a shorter time period and at lower cost than was
      previously possible. In addition, more sophisticated protein databases have
      allowed a wider variety of proteins in samples to be quantified. Novel biomarkers
      that have been identified by new proteomic technologies should be applied in a
      clinical setting.

PMID- 27718754
TI  - Special considerations for the treatment of pulmonary exacerbations in children
      with cystic fibrosis.
AB  - Introduction Cystic fibrosis (CF) is a disease characterized by recurrent flares
      of respiratory symptoms, known as pulmonary exacerbations (PExs), which have a
      cumulative, detrimental effect on lung function decline and overall mortality.
      Although much research has been done on the effects of PExs in adults with CF,
      considerably less is known about these events in young children with CF. Areas
      covered This review describes the typical presentation of PExs in children and
      their impact on long-term clinical outcomes. Traditional and new monitoring
      techniques, such as pulmonary function testing using multiple breath washout,
      radiographic modalities and microbiological screening methods are reviewed.
      Finally, the choice, administration and duration of antimicrobial treatment as
      well as the potential use of antiviral therapy is discussed. Expert Commentary
      Although it is now well recognized that a significant proportion of patients do
      not recover their lung function following PExs, to date, little progress has been
      made to improve outcomes in this group. Additional therapies, to complement
      antimicrobials, may be required to treat infection and inflammation during PExs.
      Trials of anti-inflammatories such as corticosteroids or other novel drugs need
      to be done in the setting of PExs with the goal of complete lung function
      recovery for all individuals with CF.

PMID- 27718755
TI  - Decision-making in geriatric oncology: systemic treatment considerations for
      older adults with colon cancer.
AB  - INTRODUCTION: Colon cancer is common and can be considered a disease of older
      adults with more than half of cases diagnosed in patients aged over 70 years.
      Decision-making about treatment with chemotherapy for older adults may be
      complicated by age-related physiological changes, impaired functional status,
      limited social supports, concerns regarding the occurrence of and ability to
      tolerate treatment toxicity, and the presence of comorbidities. This is
      compounded by a lack of high quality evidence guiding cancer treatment decisions
      for older adults. Areas covered: This narrative review evaluates the evidence for
      adjuvant and palliative systemic therapy in older adults with colon cancer. The
      value of an adequate assessment prior to making a treatment decision is
      addressed, with emphasis on the geriatric assessment. Guidance in making a
      treatment decision is provided. Expert commentary: Treatment decisions should
      consider goals of care, a patient's treatment preferences, and weigh up relative
      benefits and harms.

PMID- 27718756
TI  - Drug-eluting balloons in coronary interventions: the quiet revolution?
AB  - INTRODUCTION: Drug-eluting balloons (DEB) may be considered as a 'quiet
      revolution' in percutaneous coronary interventions. Early-generation DEB eluting
      paclitaxel proved to be very effective in animal models to reduce neointimal
      hyperplasia. Areas covered: Review of DEB efficacy in patients with coronary de
      novo lesions and in-stent restenosis (ISR). Expert opinion: Many randomized
      clinical trials and meta-analyses have demonstrated the value of DEB in patients
      with ISR. In this setting, DEB are safe and effective with clinical and
      angiographic results superior to plain balloon angioplasty and at least
      equivalent to first generation drug-eluting stents (DES). In selected 'de novo'
      lesions (bifurcation lesions, small vessels, diffuse disease, myocardial
      infarction) DEB represent an attractive alternative although additional evidence
      in these 'niche' indications is still required before a widespread clinical
      utilization can be recommended. Recently, new generation DEB have become
      available, offering interesting new possibilities (paclitaxel and also sirolimus)
      for coronary interventions. Further studies are required to compare the results
      of novel generation DEB with those of second-generation DES.

PMID- 27718757
TI  - Growth hormone delivery devices: current features and potential for enhanced
      treatment adherence.
AB  - INTRODUCTION: Adherence to daily growth hormone (GH) injections optimizes
      treatment benefit; however, adherence rates are sometimes poor. Reasons for poor
      adherence and persistence are multifaceted. GH injection devices are undergoing
      continual improvement to enhance adherence. Areas covered: This review evaluates
      published data on the evolution of GH injection devices to meet patients' needs
      and preferences, patients' perception of new devices and the projected impact of
      device developments on adherence. Published studies were identified through
      literature database searches including EMBASE and PubMed (January 1985-November
      2015). Expert opinion: Patient needs and preferences trend towards convenient,
      easy-to-use devices that enable self-injection, minimize injection preparation
      steps by reducing the medication reconstitution and storage requirements, and
      reduce injection pain. In comparative studies, devices that patients considered
      easier to use than comparator devices were associated with reduced handling
      errors, fear of injection (needle anxiety/needle phobia) and pain upon needle
      insertion, and were thus preferred. A combination of the following items are
      expected to increase patient motivation to better adhere to therapy and improve
      treatment outcomes: advances in GH injection devices, educating patients
      regarding injection device and injection technique, and ongoing support from
      healthcare professionals, including comprehensive education about their
      condition, medication and expected outcomes.

PMID- 27718759
TI  - Early drug development: assessment of proarrhythmic risk and cardiovascular
      safety.
AB  - INTRODUCTION: hERG assays and thorough ECG trials have been mandated since 2005
      to evaluate the QT interval and potential proarrhythmic risk of new chemical
      entities. The high cost of these studies and the shortcomings inherent in these
      binary and limited approaches to drug evaluation have prompted regulators to
      search for more cost effective and mechanistic paradigms to assess drug liability
      as exemplified by the CiPA initiative and the exposure response ICH E14(R3)
      guidance document. Areas covered: This review profiles the changing regulatory
      landscape as it pertains to early drug development and outlines the analyses that
      can be performed to characterize preclinical and early clinical cardiovascular
      risk. Expert commentary: It is further acknowledged that the narrow focus on the
      QT interval needs to be expanded to include a more comprehensive evaluation of
      cardiovascular risk since unanticipated off target effects have led to the
      withdrawal of multiple drugs after they had been approved and marketed.

PMID- 27718760
TI  - Brodalumab for the treatment of psoriasis.
AB  - INTRODUCTION: Psoriasis is a complex disease in which the alteration of the IL
      23/Th17 axis appears to be crucial for its pathogenic mechanisms, and anti-IL17
      agents are rapidly becoming important therapeutic tools. Brodalumab, a fully
      human Chinese hamster ovary cell-derived immunoglobulin G2 (IgG2) anti-IL-17RA
      monoclonal antibody, is currently the most-developed treatment that binds to the
      IL-17RA. The authors review and provide updates of efficacy and safety by several
      studies on brodalumab. Areas covered: A PubMed search was performed for relevant
      literature. Among the trials of brodalumab, the most common adverse events
      included nasopharyngitis, headache, upper respiratory tract infection, and
      arthralgia. Suicidal ideation and completed suicides had been observed in the
      brodalumab programme, although evidence to date was quoted as not suggesting a
      causal association. Expert commentary: By blocking the IL-17 receptor A,
      brodalumab antagonizes signaling from IL-17A, IL-17F, IL-17A/F and IL-25, and
      this probably contributes to the high efficacy observed in clinical trials.
      Considering the different therapeutic target and the potential biological
      implications that blocking IL-17RA instead of IL-17A might have, brodalumab may
      not necessarily belong to the same class that includes secukinumab and
      ixekizumab, but it may be classified in a distinct group.

PMID- 27718758
TI  - Challenges in treating patients with inflammatory bowel disease and concurrent
      viral hepatitis infection.
AB  - INTRODUCTION: Inflammatory bowel diseases (IBD) require long-term administration
      of immunomodulatory treatments to maintain disease remission. Due to the high
      worldwide prevalence of hepatitis B (HBV) or C (HCV) virus infections, presence
      of concurrent hepatitis can be a relevant clinical issue to manage when treating
      IBD. Areas covered: The paper summarizes epidemiological data about IBD and
      HBV/HCV infection and reviews current knowledge about the natural history of HBV
      and HCV in the IBD setting, concentrating on risk of hepatitis reactivation
      during immunosuppressive treatment. Most updated recommendations for management
      of HBV and HCV infections in IBD patients are discussed. Expert commentary: The
      development of new drugs for IBD with different molecular targets and the
      availability of potent and efficacious antiviral drugs for HBV and HCV will
      simplify management of hepatitis infection in IBD patients in the near future.

PMID- 27718761
TI  - Possible new therapeutic agents for malignant pleural mesothelioma: anti-CD26
      monoclonal antibody and naftopidil.

PMID- 27718762
TI  - Low carbohydrate diet is associated with reduced risk of metabolic syndrome in
      Tehranian adults.
AB  - This cohort study was conducted to examine the association of low carbohydrate
      diet (LCD) score with risk of incident metabolic syndrome (MetS) and its
      components after 3.6 years of follow-up in 2044 healthy adults within framework
      of the Tehran Lipid and Glucose Study. The LCD was calculated according to
      intakes of carbohydrate, monounsaturated fatty acids, refined grains, vegetable
      protein, fiber, n3/n6 polyunsaturated fatty acids ratio and glycemic load (GL),
      using a food frequency questionnaire at baseline. In the final model, after
      adjustment for age, gender, smoking status, physical activity and energy intake,
      there was significant association between LCD score and fasting plasma glucose
      (beta: -0.002, 95%CI: -0.005, -0.001), triglycerides (TGs) (beta: -0.002, 95%CI: 
      0.004, -0.001), BP (beta: -0.001, 95%CI: -0.002, 0.000), WC-BMI (beta: -0.003,
      95%CI: -0.005, -0.001) and MetS risk Z-scores (beta: -0.015, 95%CI: -0.021, 
      0.002). In conclusion, LCD may be associated with a decreased risk of MetS and
      its components in adults.

PMID- 27718763
TI  - Inhibitors of phospholipase A2 and their therapeutic potential: an update on
      patents (2012-2016).
AB  - INTRODUCTION: The regulation of the catalytic activity of the various
      phospholipase A2 enzymes is of high importance because these enzymes are involved
      in various pathological conditions such as arthritis, cardiovascular diseases,
      neurological diseases, and cancer. Thus, a great effort has been devoted in
      developing synthetic inhibitors as new agents to treat inflammatory diseases.
      Some of them have reached clinical trials. Areas covered: This review article
      discusses the phospholipase A2 inhibitors presented in patent literature from
      October 2012 to June 2016, their activities in vitro and in vivo as well as the
      results of clinical trials using synthetic PLA2 inhibitors. Expert opinion: None
      of the inhibitors studied in clinical trials have reached the market yet. The
      failure of lipoprotein-associated PLA2 inhibitor darapladib to reduce the risk of
      major coronary events suggests that this enzyme may be a biomarker of vascular
      inflammation rather than a causal pathway of cardiovascular diseases. These
      findings, together with the failure of secreted PLA2 inhibitor varespladib for
      the treatment of cardiovascular disease, indicate that deeper knowledge on these
      enzymes is needed. Inhibitors of cytosolic PLA2 are in clinical trials against
      psoriasis and atopic dermatitis.

PMID- 27718765
TI  - Vaginal alpha-lipoic acid shows an anti-inflammatory effect on the cervix,
      preventing its shortening after primary tocolysis. A pilot, randomized, placebo
      controlled study.
AB  - INTRODUCTION: Inflammation might be an important underlying cause of preterm
      birth. Our aim is to explore whether vaginal administration alpha-lipoic acid
      reduces cervical inflammation and shortening after primary tocolysis. MATERIALS
      AND METHODS: Singleton pregnancies between 24-30 weeks remaining undelivered
      after hospitalization for preterm labor were randomly allocated to placebo (20
      women, 15 analyzed) or vaginal ALA 400 mg (active ingredient 10 mg) daily (20
      women, 17 analyzed) for 30 days. A cervical swab to quantify pro-inflammatory
      (IL1, IL2, IL6, IL8, TNFalpha) and anti-inflammatory (IL4, IL10) cytokines as
      well as transvaginal ultrasound cervical length measurement (CL) were performed
      before and after treatment. RESULTS: The % changes of pro-inflammatory cytokines
      do not differ between treatment groups, while IL4 significantly increases by
      vaginal ALA in comparison to placebo (118.0 +/- 364.3% versus 29.9 +/- 103.5%, p
      = 0.012). Combined anti-inflammatory cytokines show same trend (292.5 +/- 208.5%
      versus 64.5 +/- 107.4, p = 0.03). CL remains similar in vaginal ALA group (from
      23.1 +/- 6.6 to 20.80 +/- 7.9 mm), while it significantly decreased in placebo
      group (from 20.4 +/- 6.5 to 13.8 +/- 7.5 mm, p < 0.001 versus Baseline; p = 0.003
      versus vaginal ALA). CONCLUSION: Vaginal ALA significantly stimulates anti
      inflammatory ILs in the cervix of undelivered women after a preterm labor
      episode. This effect is associated with a stabilization of the CL.

PMID- 27718766
TI  - Value of interim FDG PET/CT for predicting outcome of patients with
      angioimmunoblastic T-cell lymphoma.
AB  - Subjects were 45 patients with angioimmunoblastic T-cell lymphoma (AITL) who
      underwent 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission
      tomography/computed tomography (PET/CT) at baseline and interim after 2-4 cycles.
      Predictors of progression-free survival (PFS) and overall survival (OS) were
      assessed. Positive interim PET/CT (Deauville score >=3) was a significant
      independent predictor of poor PFS (Hazard ratio, 4.42; p=.028), and showed
      marginal significance to predict OS (p=.065). Less than 60% decrease in the
      average change of maximum standardized uptake value normalized by lean body mass
      (SULmax) also was a significant independent predictor of poor PFS (Hazard ratio,
      12.96; p=.001) and poor OS (Hazard ratio, 24.11; p=.006). Interim PET/CT has a
      significant prognostic value for predicting PFS and OS in patients with AITL.
      Deauville score and percent decrease of SULmax have the potential to be useful
      parameter in classifying patients into good and poor responders.

PMID- 27718767
TI  - Neural Activity Elicited by a Cognitive Task can be Detected in Single-Trials
      with Simultaneous Intracerebral EEG-fMRI Recordings.
AB  - Recent studies have shown that it is feasible to record simultaneously
      intracerebral EEG (icEEG) and functional magnetic resonance imaging (fMRI) in
      patients with epilepsy. While it has mainly been used to explore the hemodynamic
      changes associated with epileptic spikes, this approach could also provide new
      insight into human cognition. However, the first step is to ensure that cognitive
      EEG components, that have lower amplitudes than epileptic spikes, can be
      appropriately detected under fMRI. We compared the high frequency activities
      (HFA, 50-150[Formula: see text]Hz) elicited by a reading task in icEEG-only and
      subsequent icEEG-fMRI in the same patients ([Formula: see text]), implanted with
      depth electrodes. Comparable responses were obtained, with 71% of the recording
      sites that responded during the icEEG-only session also responding during the
      icEEG-fMRI session. For all the remaining sites, nearby clusters (distant of
      7[Formula: see text]mm or less) also demonstrated significant HFA increase during
      the icEEG-fMRI session. Significant HFA increases were also observable at the
      single-trial level in icEEG-fMRI recordings. Our results show that low-amplitude
      icEEG signal components such as cognitive-induced HFAs can be reliably recorded
      with simultaneous fMRI. This paves the way for the use of icEEG-fMRI to address
      various fundamental and clinical issues, notably the identification of the neural
      correlates of the BOLD signal.

PMID- 27718768
TI  - Influence of the Great East Japan Earthquake and the Fukushima Daiichi nuclear
      disaster on the birth weight of newborns in Fukushima Prefecture: Fukushima
      Health Management Survey.
AB  - OBJECTIVE: The Great East Japan Earthquake and Fukushima Daiichi nuclear disaster
      occurred on 11 March 2011. We investigated the incidence of SGA (small for
      gestational age) in the Fukushima Prefecture in newborns delivered by women who
      were pregnant at the time of the disasters and identified any risk factors for
      SGA. METHODS: Subjects were women who were pregnant at the time of the disasters.
      Questionnaires were sent to the women who lived in the Hamadori area (seaside and
      near to the nuclear power plant) at the time of the disasters as well as to a
      control group of women who lived outside the Hamadori area. The incidence of SGA
      was compared. Logistic regression analysis was performed to identify the risk
      factors for SGA. RESULTS: In total, 325(5.6%) women had infants with SGA. Neither
      area nor the trimester of pregnancy at the time of the disasters influenced the
      incidence of SGA. Pregnancy-induced hypertension (PIH) was higher in the SGA
      group. PIH was found to be an independent risk factor for SGA. CONCLUSION: We
      found no evidence that the Great East Japan Earthquake and the Fukushima Daiichi
      nuclear disaster increased the incidence of SGA in the Fukushima Prefecture.

PMID- 27718769
TI  - Podophyllum hexandrum ameliorates endosulfan-induced genotoxicity and
      mutagenicity in freshwater cyprinid fish crucian carp.
AB  - CONTEXT: Medicinal plants continue to act as a repository for novel drug leads
      with novel mechanisms of action. Podophyllum hexandrum Royale (Berberideceae)
      treats diverse conditions in folk medicine. OBJECTIVE: The antimutagenic
      potential of P. hexandrum was evaluated against endosulfan-induced clastogenicity
      in a piscine model by cytogenetic endpoints. MATERIALS AND METHODS: Podophyllum
      hexandrum rhizomes were subjected to successive solvent extraction. Fish were
      exposed to hexane, chloroform, ethyl acetate, methanol and aqueous extracts (15
      mg/L each) of plant and endosulfan (0.05 mg/L) alone followed by their
      combination for antimutagenicity estimates. Chromosomal aberrations (CA) were
      made from kidney cells and micronuclei (MN) slides from peripheral blood
      erythrocytes at 48, 72 and 96 h. Antioxidant activity was analyzed by the DPPH
      assay. Phytochemical analyses were carried out using chromatographic and
      spectroscopic techniques. RESULTS: Endosulfan induced significant (p < .05) MN,
      authenticated by scanning electron microscopy, and CA in a time-dependent manner.
      However, methanol and ethyl acetate extracts revealed ameliorating effects. The
      column eluted methanolic fraction-2 (ME-F2) showed highest reduction profile of
      83 and 84% in CA and MN, followed in its extent (73 and 72%) by ethyl acetate
      fraction-4 (EE-F4). ME-F2 and EE-F4 showed three and six major peaks when
      analyzed by GC-MS. To explore possible mechanism of action, ME-F2 showed potent
      antioxidant potential and strong correlation (R2 = .900) with antimutagenic
      activity, whereas EE-F4 seemed to act through a different mechanism. DISCUSSION
      AND CONCLUSION: This study confirms the antimutagenic potential of the subject
      plant with the identification of some novel compounds, justifying their use in
      folk medicine, and their corresponding benefit to mankind.

PMID- 27718771
TI  - Bolus feeding has no effect on cerebral hemodynamics, irrespective of gestational
      age.
AB  - OBJECTIVE: By multichannel near-infrared spectroscopy, we studied if gestational
      age has any influence on preterm cerebral hemodynamics, during bolus feeding.
      METHODS: Oxy-haemoglobin (HbO2), as cerebral blood flow estimate, and the ratio
      between HbO2 and total haemoglobin (HbO2/HbTot), as cerebral oxygenation
      estimate, were assessed in 40 stable premature infants, during a 10 min bolus
      feeding. RESULTS: We found no effect of any of the gestational ages studied (25
      34 weeks) either on cerebral blood flow or on oxygenation, during a bolus feeding
      procedure. CONCLUSIONS: Bolus feeding appears not to affect cerebral hemodynamics
      of uncritically preterm infants, irrespective of gestational age.

PMID- 27718772
TI  - Relationship Between Frequent Recreational Cannabis (Marijuana and Hashish) Use
      and Periodontitis in Adults in the United States: National Health and Nutrition
      Examination Survey 2011 to 2012.
AB  - BACKGROUND: Recreational use of cannabis, following its legalization in some
      countries, poses emergent oral and periodontal health concerns. The objective of
      this study is to examine the relationship between frequent recreational cannabis
      (FRC) (marijuana and hashish) use and periodontitis prevalence among adults in
      the United States. METHODS: Data from the National Health and Nutrition
      Examination Survey (NHANES) 2011 to 2012 were analyzed. Primary outcome
      (periodontitis) was defined using the Centers for Disease Control and
      Prevention/American Academy of Periodontology classification as well as
      continuous measurements of probing depth (PD) and clinical attachment loss (AL).
      Exposure of interest was self-reported cannabis use, defined as "FRC use" versus
      "non-FRC use." Bivariate and multivariable regression models were performed using
      the entire analytical sample (model 1) as well as those who had never used
      tobacco (never-users) (model 2). RESULTS: Of 1,938 participants with available
      cannabis use data and essential covariates, 26.8% were FRC users. Mean number of
      sites per participant with PD >=4, >=6, and >=8 mm and AL >=3, >=5, and >=8 mm
      was significantly higher among FRC users than among non-FRC users (mean
      difference in number of PD sites: 6.9, 5.6, and 5.6; P <0.05; mean difference in
      number of AL sites: 12.7, 7.6, and 5.6; P <0.05). Average AL was higher among FRC
      users than among non-FRC users (1.8 versus 1.6 mm; P = 0.004). Bivariate analysis
      revealed positive (harmful) association between FRC use and severe periodontitis
      in the entire sample (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.3 to
      2.4; P = 0.002) as well as in never-smokers (OR: 2.0, 95% CI: 1.2 to 3.5; P =
      0.01). This association was retained in multivariable models adjusted for
      demographics (age, sex, race/ethnicity, and income level), alcohol and tobacco
      use, diabetes mellitus, and past periodontal treatment (model 1: adjusted OR
      [aOR]: 1.4, 95% CI: 1.1 to 1.9; P = 0.07; model 2: aOR: 1.9, 95% CI: 1.1 to 3.2;
      P = 0.03). CONCLUSION: FRC use is associated with deeper PDs, more clinical AL,
      and higher odds of having severe periodontitis.

PMID- 27718773
TI  - Difference of hospital charges for stroke inpatients between hospitals with
      different levels and therapeutic modes in Beijing, China.
AB  - OBJECTIVES: The present study analyzed the hospital charges for stroke patients
      in China and determined the factors associated with hospital costs. METHODS:
      Medical records of hospitalized patients with a primary diagnosis of acute stroke
      were collected from 121 hospitals in Beijing (2012). Distribution characteristics
      of hospital charges for different stroke types, hospital levels and types were
      studied. Factors influencing total hospital charges were analyzed. RESULTS: 60.8%
      of the 94 906 stroke patients were male and the mean age of these patients was
      66.5 +/- 13.2 years. The median length of hospital stay (LOHS) for these patients
      was 14 d (interquartile range, IQR 9-19). The mean hospital charge per patient
      was 19 270 Chinese Yuan. Forty-five percent of these charges were for medicine,
      18% for laboratory and examination, 16% for material, 15% for therapy, 5% for
      service and 1% for blood product. The mean hospital charge for patients suffering
      from hemorrhagic stroke was significantly more than ischemic stroke (34 937 vs.
      17 049, p < 0.001), and was significantly more for Level 3 than Level 2 hospitals
      (23 762 vs. 14 554, p < 0.001). LOHS, hospital level and stroke severity were key
      determinants of the hospital charge. CONCLUSIONS: Though hospital charges for
      stroke patients in China were low, it brought a heavy economic burden for the
      larger stroke population. Medicine accounted for the largest percentage of
      hospital charges in China. LOHS emerged to be the main predictor of the cost.
      Decreasing medicine charge and LOHS might be strategies to decrease hospital
      charges and reduce economic burden of stroke in China.

PMID- 27718774
TI  - External cephalic version in premature rupture of membranes: a systematic review.
AB  - BACKGROUND: External cephalic version (ECV) increases the likelihood of a vaginal
      delivery in patients with breech presentation. Our objective was to determine the
      rate of cephalic vaginal delivery in women undergoing ECV after PROM. METHODS: We
      performed a systematic review of all case reports, case series and clinical
      trials of patients undergoing an ECV after PROM >= 24 weeks. Maternal
      demographics and outcome data were obtained. The primary outcome was rate of
      cephalic vaginal delivery. Statistical analysis was performed for continuous
      outcomes by calculating mean and standard deviations for appropriate variables.
      RESULTS: The systematic review yielded six papers with 13 case reports and no
      clinical trials of ECV after PROM. The rate of success to cephalic presentation
      was 46.1% (six of 13 cases), with a subsequent vaginal delivery rate of 23.1%
      (three of 13 cases). The rate of umbilical cord prolapse was 33.3% (two of six
      cases). CONCLUSIONS: ECV after PROM has been reported in 13 cases in the
      literature. For the cases reported, 46.1% of ECV were successful in turning to
      cephalic position, but only 23.1% resulted in a vaginal delivery. There was a
      33.3% incidence of umbilical cord prolapse. Given the high rate of umbilical cord
      prolapse, it would be imperative to offer an ECV in the setting of PROM only at
      an institution that has the ability to perform the indicated emergent cesarean
      delivery and only after appropriate counseling.

PMID- 27718775
TI  - Breaking the cycle of hair breakage: pearls for the management of acquired
      trichorrhexis nodosa.
AB  - Acquired trichorrhexis nodosa (TN) is a common cause of hair loss for patients of
      all ethnicities. It is especially prevalent in black patients with tightly curled
      hair types and can present unique diagnostic and therapeutic challenges due to
      structural differences in these hair types and the combination of various hair
      care and styling practices that contribute to hair damage. While scalp biopsies
      can help rule out other etiologies of hair loss, there is a paucity of histologic
      findings in acquired TN, making this primarily a clinical diagnosis. Instead of
      more traditional prescription based therapies, the management of this form of
      hair loss emphasizes protecting the hair shaft and minimizing further damage
      through the development of a healthy hair care regimen. This involves appropriate
      selection and use of cleansing products and conditioning agents that help protect
      the hair from the insults of daily grooming. This paper will review the current
      literature on acquired TN and will provide guidelines and recommendations for
      management by reviewing the different types of cleansing and conditioning
      products that can be used to prevent and/or halt the progression of hair
      breakage.

PMID- 27718776
TI  - Fetal intracranial hemorrhage: sonographic criteria and merits of prenatal
      diagnosis.
AB  - PURPOSE: To determine the sonographic criteria for diagnosis of fetal
      intracranial hemorrhage (ICH), using both gray scale ultrasound, and tomographic
      ultrasound imaging (TUI). MATERIALS AND METHODS: A prospective multicenter study,
      recruiting patients at risk of fetal ICH over four years. All cases with fetal
      ICH had serial ultrasound assessments, including TUI, fetal and postnatal MRIs.
      RESULTS: Twenty-one patients were diagnosed with fetal ICH, two cases had
      extracerebral (subdural) hemorrhage, 16 cases had intracerebral
      (intraventricular) hemorrhage and three cases had combined hemorrhage. The mean
      gestational age at which they were diagnosed was 29.8 +/- 5.2 weeks. Seventy-six
      percent of cases had no identifiable risk factors. IUGR was associated with 57.9%
      of cases. Using grey scale ultrasound, we demonstrated clear cut sonographic
      criteria for diagnosis of fetal ICH. TUI enabled us to detect some midline
      cerebral lesions not detected by grey scale 2D ultrasound alone. Fetal and
      postnatal MRI confirmed those findings. CONCLUSION: Ultrasonography can be used
      in the detection, classification and monitoring the progression of various types
      of ICH. TUI is an additional diagnostic tool that might help to detect the exact
      size, and extent of those lesions. Fetal MRI is not superior, but might aid in
      the diagnosis.

PMID- 27718777
TI  - Physical performance measures for predicting outcome in cancer patients: a
      systematic review.
AB  - BACKGROUND: Decision making regarding cancer treatment is challenging and there
      is a need for clinical parameters that can guide these decisions. As physical
      performance appears to be a reflection of health status, the aim of this
      systematic review is to assess whether physical performance tests (PPTs) are
      predictive of the clinical outcome and treatment tolerance in cancer patients.
      METHODS: A literature search was conducted on 2 April 2015 in the electronic
      databases Medline and Embase to identify studies focusing on the association
      between objectively measured PPTs and outcome. No limitations in language or
      publication dates were applied. RESULTS: The search retrieved 9680 articles, 16
      publications were included involving 4187 patients with various cancer types and
      different treatments. Reported median or mean age varied from 58 to 78 years.
      Nine studies used the Timed Up & Go (TUG) test, five the Short Physical
      Performance Battery (SPPB) and five studies focused on gait speed. Poorer TUG,
      SPPB and gait speed outcome were associated with decreased survival. TUG, SPPB
      and gait speed were also associated with treatment-related complications.
      Furthermore, two studies reported an association between poorer TUG and SPPB
      outcome with higher rates of functional decline. CONCLUSION: PPTs appear to show
      a significant correlation with survival and these tests could be used as a
      prognostic tool, particular for older adult patients. A less explicit correlation
      for treatment-related complications and functional decline was also found. To
      optimize decision making, future research should focus on developing and
      validating individualized treatment algorithms that incorporate PPTs in addition
      to cancer- and treatment-related variables.

PMID- 27718778
TI  - Long-term refractive status of preterm infants from singleton and multiple
      pregnancies.
AB  - OBJECTIVE: To study the effect of plurality on refractive status in former
      preterm infants at age 8-12 years. METHODS: Refraction was compared in singletons
      and multiples, in very low birth weight infants (VLBW, <1500 g) at age 6 months
      and 8-12 years. Preterm infants were compared with a group of term infants.
      RESULTS: Thirty-seven of 104 (36%) VLBW infants were multiples. Comparison of
      refraction between singletons and multiples revealed no difference at age 6
      months, while at age 8-12 years, multiples had significantly more refractive
      errors (singletons 28% versus multiples 54% p = 0.01), particularly myopia. In
      preterms, refractive status at age 6 months and multiple birth were significant
      predictors of refraction at 8-12 years, while birth weight (BW) and retinopathy
      of prematurity (ROP) were not predictive. Refractive errors were significantly
      more common in preterms (37%) than in term-born children (14%) (p = 0.0002).
      Overall, refraction moved from predominantly hyperopic at 6 months to normal or
      myopic at age 8-12 years in preterm. CONCLUSIONS: Multiple gestation in preterms
      is associated with increased risk for refractive errors, particularly myopia in
      childhood. Refraction in preterms during childhood progresses from hyperopia to
      myopia. Former preterms have more refractive errors than children born at term
      born children.

PMID- 27718779
TI  - Eosinophilia as the presenting sign in pancreatic cancer: an extremely rare
      occurrence.
AB  - A case of pancreatic adenocarcinoma diagnosed following work up for eosinophilia
      is reported. A 68-year-old female was referred to our Hematology clinic for an
      absolute eosinophil count of 1869 per microliter. No allergic signs or symptoms
      were reported. Laboratory studies for parasitic infestations autoimmune disease
      and collagen vascular disease were negative. Computed tomography of the abdomen
      revealed a mass in the neck of the pancreas with fine needle aspiration biopsy
      consistent with adenocarcinoma. The patient received one cycle of modified
      FOLFIRINOX with complete resolution of the eosinophilia. There are rare case
      reports of tumor-associated blood eosinophilia in solid malignancies. The finding
      may be indicative of rapid disease progression and poor prognosis. Our case is
      the third in published English literature with eosinophilia being the initial
      finding in pancreatic cancer.

PMID- 27718780
TI  - Preparation and optimization of glyceryl behenate-based highly porous pellets
      containing cilostazol.
AB  - The aim of this study was to prepare a highly porous multiparticulate dosage form
      containing cilostazol for gastroretentive drug delivery. The floating pellets
      were prepared with glyceryl behenate as a matrix former and camphor as a
      sublimating agent by extrusion/spheronization and sublimation under vacuum.
      Granules prepared with sublimation at 60  degrees C displayed a slower
      dissolution rate and smoother surface morphology than those prepared at lower
      temperatures. This was unexpected as the reported melting point of glyceryl
      behenate is higher than 69  degrees C. The DSC study revealed that melting began
      at a lower temperature owing to the multicomponent property of glyceryl behenate,
      which led to a sintering effect. The prepared pellets were spherical with
      unimodal size distribution. They also had porous structures with increased
      porosity, which led to immediate buoyancy. As cilostazol is a hydrophobic drug
      that has an erosion-based release mechanism, drug release profile was highly
      correlated with the percentage of disintegrated pellets. Various excipients were
      added to the glyceryl behenate-based formulation to increase the floating
      duration. When hydroxyethyl cellulose was added to the glyceryl behenate-based
      pellets, acceptable dissolution rate and buoyancy were acquired. This system
      could potentially be used for gastroretentive delivery of various hydrophobic
      drugs, which was generally considered difficult.

PMID- 27718782
TI  - Comparative pharmacokinetics of three SGLT-2 inhibitors sergliflozin,
      remogliflozin and ertugliflozin: an overview.
AB  - 1. Several sodium-glucose cotransporter-2 (SGLT-2) inhibitors are in clinical use
      for the management of type 2 diabetes. The objectives of the current review were:
      (a) to provide a comparative pharmacokinetics including absorption, distribution,
      metabolism and excretory (ADME) profiles of three SGLT-2 inhibitors namely:
      sergliflozin, remogliflozin and ertugliflozin; (b) to provide some perspectives
      on possible developmental issues. 2. Based on the half-life (t1/2) values
      observed in humans, the rank order of the three SGLT-2 inhibitors was
      ertugliflozin (16 h) > remogliflozin (2-4 h) > sergliflozin (1-1.5 h). Therefore,
      while once a day dosing of ertugliflozin is possible, the other two drugs need to
      be dosed more frequently. Perhaps, the short t1/2 of sergliflozin may have
      contributed for its discontinuation. 3. Although there was paucity of published
      data on the metabolism, transporter related and excretory aspects for
      sergliflozin, the other two drugs provided a differentiating profile. However,
      the compiled data suggested that there may be a minimal or no risk of
      pharmacokinetic drug interaction issues associated with any of the reviewed
      drugs. 4. Because of the crowded development pipeline and approved SGLT-2
      inhibitors, the safety and efficacy of sergliflozin, remogliflozin and
      ertugliflozin appear to be a key from differentiation perspective.

PMID- 27718781
TI  - Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.
AB  - BACKGROUND: Sunitinib, a vascular endothelial growth factor pathway inhibitor, is
      an effective treatment for metastatic renal-cell carcinoma. We sought to
      determine the efficacy and safety of sunitinib in patients with locoregional
      renal-cell carcinoma at high risk for tumor recurrence after nephrectomy.
      METHODS: In this randomized, double-blind, phase 3 trial, we assigned 615
      patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive
      either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule
      for 1 year or until disease recurrence, unacceptable toxicity, or consent
      withdrawal. The primary end point was disease-free survival, according to blinded
      independent central review. Secondary end points included investigator-assessed
      disease-free survival, overall survival, and safety. RESULTS: The median duration
      of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not
      reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo
      group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data
      were not mature at the time of data cutoff. Dose reductions because of adverse
      events were more frequent in the sunitinib group than in the placebo group (34.3%
      vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1%
      vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group
      (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group
      (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse
      events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths
      were attributed to toxic effects. CONCLUSIONS: Among patients with locoregional
      clear-cell renal-cell carcinoma at high risk for tumor recurrence after
      nephrectomy, the median duration of disease-free survival was significantly
      longer in the sunitinib group than in the placebo group, at a cost of a higher
      rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number,
      NCT00375674 .).

PMID- 27718783
TI  - Genetic, metabolic and endocrine aspect of intrauterine growth restriction: an
      update.
AB  - Intrauterine growth restriction (IUGR) is defined as growth of fetus below its in
      utero growth potential. Small for gestational age (SGA) is defined as newborn
      with birth weight less than 10th centile as per the gestational age, sex and
      race. There exists major difference between IUGR and SGA. IUGR infants have
      multiple short-term and long-term complications and IUGR is a silent cause of
      various morbidities and mortalities in these infants. IUGR/SGA is usually end
      results of maternal, placental, fetal and genetic causes. With the advance of
      molecular biology, the list genetic cause of IUGR is increasing and these genetic
      causes include maternal, placental and fetal genes. Several metabolic and
      endocrinal causes are also responsible to cause IUGR. In this review, we will try
      to cover genetic, metabolic and endocrinal factors that are responsible for IUGR.

PMID- 27718785
TI  - Conferences.
AB  - April 7-9 Bled, Slovenia The fifth European conference of the Association for
      Common European Nursing Diagnoses, Interventions and Outcomes (ACENDIO). This is
      an international organisation that aims to promote the development of a common
      professional language for nursing.

PMID- 27718786
TI  - ?
AB  - Clean start: head of infection control at Carmarthenshire NHS Trust Sharon Evans
      helped launch the National Patient Safety Agency cleanyourhands campaign in Wales
      last month. Chief nursing officer Rosemary Kennedy said: 'Patients need to be
      confident enough to question staff if they believe that they haven't washed their
      hands between seeing patients. These simple actions can have a major effect.'
      Picture reproduced courtesy of the Llanelli Star.

PMID- 27718787
TI  - CNO launches mental health nursing review.
AB  - The Department of Health last month launched a major review of mental health
      nursing.

PMID- 27718788
TI  - Senior nurse and chief exec pay gap widens.
AB  - The pay of senior nurses is falling increasingly far behind that of their chief
      executives, according to research published last month.

PMID- 27718784
TI  - Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck.
AB  - BACKGROUND: Patients with recurrent or metastatic squamous-cell carcinoma of the
      head and neck after platinum chemotherapy have a very poor prognosis and limited
      therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal
      antibody, was assessed as treatment for this condition. METHODS: In this
      randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients
      with recurrent squamous-cell carcinoma of the head and neck whose disease had
      progressed within 6 months after platinum-based chemotherapy to receive nivolumab
      (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single
      agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end
      point was overall survival. Additional end points included progression-free
      survival, rate of objective response, safety, and patient-reported quality of
      life. RESULTS: The median overall survival was 7.5 months (95% confidence
      interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0
      to 6.0) in the group that received standard therapy. Overall survival was
      significantly longer with nivolumab than with standard therapy (hazard ratio for
      death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year
      survival rate were approximately 19 percentage points higher with nivolumab than
      with standard therapy (36.0% vs. 16.6%). The median progression-free survival was
      2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to
      3.1) with standard therapy (hazard ratio for disease progression or death, 0.89;
      95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months
      was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was
      13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment
      related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the
      nivolumab group versus 35.1% of those in the standard-therapy group. Physical,
      role, and social functioning was stable in the nivolumab group, whereas it was
      meaningfully worse in the standard-therapy group. CONCLUSIONS: Among patients
      with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck,
      treatment with nivolumab resulted in longer overall survival than treatment with
      standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141
      ClinicalTrials.gov number, NCT02105636 .).

PMID- 27718790
TI  - ?
AB  - EVER WONDERED whether it's worth spending large amounts of money on overseas
      study tours to learn from different organisations, in different countries and
      cultures?

PMID- 27718789
TI  - Concerns raised over loss of nurse advisers.
AB  - Uncertainty surrounds how ministers will receive independent and comprehensive
      advice on nursing and midwifery after the imminent abolition of the Standing
      Nursing and Midwifery Advisory Committee (SNMAC).

PMID- 27718791
TI  - Going global.
AB  - TRADITIONALLY, nurse leaders in the UK have tended to shy away from professional
      visits abroad.

PMID- 27718792
TI  - Managing the aftershock.
AB  - I'M SURE that if I asked you what you remember about September 11 2002, you would
      have little difficulty recalling that horrific day when two aeroplanes crashed
      into New York's Twin Towers.

PMID- 27718793
TI  - Maggie Stubbs.
AB  - What does your job involve? I am a nurse, midwife and health visitor by
      background and at present I provide effective leadership to nurses, midwives and
      allied health professionals.

PMID- 27718794
TI  - Vantage point.
AB  - WHAT'S IN A NAME? Nurses love titles: 'advanced nurse practitioner', 'specialist
      nurse', 'emergency nurse practitioner' and, hot off the press, 'community
      matron'.

PMID- 27718795
TI  - ?
AB  - Promotions / new appointments.

PMID- 27718797
TI  - Community spirit.
AB  - LAST MONTH, the health department published a 'blue- print for developing the
      role of community matrons'.

PMID- 27718796
TI  - ?
AB  - Violent times: director of nursing and midwifery at Gateshead Health NHS
      Foundation Trust Shirley Richardson (right) raises the growing problem of violent
      and aggressive patients during a visit by RCN president Sylvia Denton.
      Initiatives at the trust, said to be among the most 'proactive' in the country,
      include the introduction of closed circuit TV, electronic doors, personal alarms
      for staff and an on-site community beat police officer. But some staff believe
      that levels of violence will increase with the new licensing laws that came into
      force last month to allow round-the-clock drinking.

PMID- 27718799
TI  - Employers assembly.
AB  - Seven senior nurses have taken their seats at the first meeting of NHS Employers
      assembly.

PMID- 27718798
TI  - Nurse-patient ratios.
AB  - Nurses have voted for the introduction of nurse-patient ratios, according to RCN
      Scotland.

PMID- 27718800
TI  - Reading the signs.
AB  - The Commons health committee's recent report on elder abuse begins with a telling
      comparison between two tragic cases. One concerned a child, Victoria Climbie,
      whose torture and death at the hands of a relative received widespread coverage;
      and the other, a 78-year-old woman, Margaret Panting, who suffered 'unbelievable
      cruelty' while living with relatives. Postmortem examination showed 49 injuries
      on her body including cuts and cigarette burns. There was little press interest
      and no one was charged over her death because there was insufficient evidence to
      determine how she died.

PMID- 27718801
TI  - Websites.

PMID- 27718802
TI  - Editorial.
AB  - It is difficult to ignore the fact that two of the Royal College's three royal
      patrons have died in the last few weeks. It has long been passe to admire the
      traditions of royalty amongst the chattering classes. The 'scandals' of recent
      years and the nature of tabloid journalism in the 'red tops' and elsewhere has
      only helped to lower regard for royalty - or so we were told. Looking back over
      history, the royal family has always behaved in a way that would attract public
      comment. Now however, there is more comment than ever before. Why, therefore, add
      to the volume with an editorial?

PMID- 27718804
TI  - NHS pay scheme will be implemented early.
AB  - Implementation of the new NHS pay system when it is agreed will begin with a
      period of early implementation, according to a Department of Health HR bulletin.
      In England 'early implementation' sites will be chosen on the basis of clear
      criteria and subject to close monitoring and evaluation before the system is
      rolled out across the NHS.

PMID- 27718805
TI  - New regulations for professionals.
AB  - NHS professionals should be subject to the new nurses agencies regulations being
      introduced this summer, according to the Federation of Inde- pendent Nursing
      Agencies (FINA).

PMID- 27718806
TI  - New survey finds highest standard of care is offered by nurse practitioners.
AB  - Nurse practitioners appear to provide care that is at least as good as, if not
      better than, that offered by doctors. Researchers at the University of Bristol
      carried out a meta-analysis of 11 randomised controlled trials (RCTs) and 23
      observational studies and concluded that the 'review lends support to an
      increased involvement of nurse practitioners'.

PMID- 27718807
TI  - The Bullying Culture: Cause, Effect, Harm reduction The Bullying Culture: Cause,
      Effect, Harm reduction Ruth Hadikin ; Muriel ODriscoll Butterworth Heinemann 179
      L13.50 0 75065 201 2 0750652012 [Formula: see text].
AB  - The Bullying Culture, written by Ruth Hadikin and Muriel O'Driscoll, focuses on
      bullying in midwifery. The authors make this text salutary reading for all nurses
      by sharing with the reader a number of case studies that expose the many ugly
      faces of bullying.

PMID- 27718808
TI  - Creative Supervision Creative Supervision Mooli Lahad Jessica Kingsley Publishers
      128 L14.95 1 85302 828 2 1853028282 [Formula: see text].
AB  - Understanding values and beliefs is an area that Mooli Lahad, author of Creative
      Supervision, explores from a different perspective to most of the texts
      considered to be closer to the mainstream. Lahad presents a range of approaches
      to supervision and reinforces their effectiveness by providing a number of case
      studies that include outcomes. If you are not prepared to let the creative side
      of your brain run free while you are reading Creative Supervision, then this is
      not the book for you. If however, exposure to creative thinking and problem
      solving has you hooked then this will be an essential addition to your bookshelf.

PMID- 27718809
TI  - Conferences.
AB  - A practical guide to improving elderly care 30 May Delivering the NSF and
      supporting clinical governance Venue: The Royal College of Physicians, London
      Details: Healthcare Events Tel: 020 8541 1399 Fax: 020 8547 2300 Email:
      info@healthcare-events.co.uk Website: www.healthcare-events.co.uk.

PMID- 27718811
TI  - Nurse nurse.

PMID- 27718810
TI  - Clinical governance in healthcare practice Clinical governance in healthcare
      practice Thoreya Swage Butterworth Heinemann 254 pages L18.99 0 75064 453 2
      0750644532 [Formula: see text].
AB  - If logic and critical thinking is more your scene than fantasy and imagination
      you will probably find Clinical Governance in Healthcare Practice more suitable
      for your tastes.

PMID- 27718813
TI  - Resources.
AB  - Nominations are invited for Fellowship and Honorary Fellowship of the RCN to be
      received by 17 May 2002. Fellowships and Honorary Fellowships of the RCN are an
      honour awarded by Council.

PMID- 27718812
TI  - The road ahead.
AB  - THE PROVISION of health and social care is a labour intensive enterprise in which
      the workforce is the key to modernisation. It not only delivers services but also
      acts as the arbiter of its own quality.

PMID- 27718814
TI  - Nurses to be examined annually.
AB  - Annual physical and mental examination of nurses may be introduced under
      proposals being considered by the Nursing and Midwifery Council (NMC). They may
      have to undergo a medical examination and produce a certificate detailing their
      criminal record to comply with tighter guidelines on fitness to practise.

PMID- 27718815
TI  - The problem of bullying.
AB  - BACK IN the late 1990s we heard of the government's desire to turn the NHS into
      something that was modern and dependable. National clinical standards were to be
      the way forward, we were to enter a new era of performance monitoring and the
      culture in the NHS was to change.

PMID- 27718816
TI  - ?
AB  - This study employed ethnography to investigate the cultural dimensions of
      communication between student nurses and older people in an Irish setting. The
      data collection methods included participant observation and semi-structured
      interviews. The four themes identified from the data were: types of
      communication; modes of communication; factors which hinder or enhance
      communication; and the student nurses' approaches to communicating with the older
      person.

PMID- 27718818
TI  - Introduction to research for midwives Introduction to research for midwives Third
      edition Colin Rees Churchill Livingstone L24.99 260pp 9780702034909 0702034908
      [Formula: see text].
AB  - THE THIRD edition of this publication takes into account the developments in
      evidence based practice in clinical care. The book is aimed at introducing
      research methods, critical evaluation of research and application to midwifery
      practice. It contains references to more detailed research textbooks for nurses
      and midwives.

PMID- 27718817
TI  - United front may help prevent crisis.
AB  - Warnings of looming crisis are all around us, including within services for older
      people. Recent reports warn that the care home sector is reaching a critical
      juncture and, without long-term planning and investment, crisis will turn to
      meltdown ( Burstow 2003 ). In the past five years something like 50,000 long-term
      care beds have been lost and now, according to the National Audit Office, tens of
      thousands of older people each year find themselves unable to leave hospital
      because there is insufficient post-hospital care (see page five ). Emergency
      hospital readmissions have increased by nearly 20 per cent over the past two
      years and the reality of intermediate care has yet to live up to the policy
      rhetoric.

PMID- 27718819
TI  - Notice board.
AB  - Courses, events, grants, and awards to progress your career.

PMID- 27718821
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27718820
TI  - Lessons from the Olympics.
AB  - The late summer was an exciting time for following the considerable achievements
      of Team GB. All the medallists shared a commitment, a drive and a willingness to
      make sacrifices to be the very best at what they do. For each of them, nothing
      less than the best was acceptable, and the result was an unprecedented level of
      success. This created huge pride across Britain and, in keeping with the spirit
      of the Olympics, the example set by the athletes and paralympians should inspire
      the next generation.

PMID- 27718822
TI  - Spiritual care for healthcare professionals Spiritual care for healthcare
      professionals Tom Gordon , Ewan Kelly and David Mitchell Radcliffe L24.99 | 172pp
      9781846194559 1846194555 [Formula: see text].
AB  - THIS BOOK reflects on clinical practice and offers an outline of approaches to
      spiritual care. Thirteen chapters are divided into subsections dealing with: the
      art of spiritual care, assessing and responding to spiritual needs, working with
      the complexities of spiritual care, the personal impact of spiritual care and the
      role of the chaplain.

PMID- 27718823
TI  - Making sense of research Making sense of research Fourth edition Pam Moule and
      Gill Hek Sage Publications L20.99 200pp 9781849207799 1849207798 [Formula: see
      text].
AB  - EACH SECTION of this publication, which is intended as an introduction to
      research, is easy to read to gain the 'bones' of the activities related to
      investigation. Sections include the nature of knowledge in health and social
      care, the research process, ethics, literature reviewing, data collection methods
      and analysis.

PMID- 27718824
TI  - Working in the realworld.
AB  - Q: What does your job entail?

PMID- 27718825
TI  - ?
AB  - Depression, delirium or dementia is a factor for almost half of older people in
      acute medical and surgical wards. Psychiatric symptoms often persist after
      discharge and can affect functional outcome, length of stay and mortality.

PMID- 27718826
TI  - Vive la revolution!
AB  - July 2003 marked the mid-point of The European Year of People with Disabilities -
      and discrimination in the NHS is alive and kicking. As with other European or
      international years, it aims primarily to raise awareness, consciousness and
      conscience at all levels, and ultimately promote dignity and human rights.

PMID- 27718828
TI  - Minority ethnic focus for new programme.
AB  - Nurses from black and minority ethnic backgrounds who aspire to directorship
      roles are being targeted in the latest programme from the NHS Modernisation
      Agency leadership centre. The national programme is being launched this month at
      a conference in Birmingham.

PMID- 27718827
TI  - NMC Consultations: is the devil in the detail?
AB  - Throughout the summer the Nursing and Midwifery Council (NMC) has been seeking
      views on three consultation documents (NMC 2003a, NMC 2003b, NMC 2003c). These
      documents represent the very foundations of our profession.

PMID- 27718829
TI  - Trust me, I'm a nurse.
AB  - It's Saturday morning and I've been called to see Edith Smith, who has been
      admitted to a care home for two weeks' rehabilitation following a hip
      replacement. Everything has being going well but today there are problems. She is
      in bed and complaining of pain in her hip. I examine her and it's clear that her
      hip replacement has dislocated. She confirms the diagnosis, saying: 'I think my
      new hip has slipped, don't you?'

PMID- 27718830
TI  - Unions raise concerns as pay consultation closes.
AB  - Nursing unions have raised concerns over government proposals on modernising pay
      and contractual arrangements for NHS managers. Consultation on the proposals
      closed on September 30, and unions were finalising their responses as Nursing
      Management went to press.

PMID- 27718831
TI  - Modern matrons are victims of their own success.
AB  - Modern matrons at Whipps Cross University Hospitals NHS Trust, London, have
      become the victims of their own success, the conference heard.

PMID- 27718832
TI  - College campaign aims to fill senior health service posts.
AB  - The RCN is launching a nursing leadership campaign this month aimed at increasing
      the number of nurses in senior management posts.

PMID- 27718833
TI  - Conferences.

PMID- 27718834
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27718836
TI  - New chair for director association.
AB  - Director of nursing at Guy's and St Thomas' Hospital NHS Trust, London, Irene
      Scott (pictured left) has succeeded Stephen Moss as chair of the Nurse Directors
      Association (NDA).

PMID- 27718835
TI  - Editorial.
AB  - This month, Nursing Management welcomes on board a new columnist, US-based
      journalist Suzanne Gordon, with the aim opening a dialogue between both sides of
      the Atlantic about what is going on in health care.

PMID- 27718837
TI  - Survey reveals 'progress' and 'challenges'.
AB  - Two out of five modern matrons believe they are unsupported at work, according to
      conference delegates. A poll of 85 modern matrons and senior nurses attending the
      conference in London revealed that 34 felt they are not adequately supported.

PMID- 27718838
TI  - RCN welcomes rise in nurse manager numbers.
AB  - A 20 per cent rise in the number of nurse managers in England reflects a welcome
      return to valuing the nursing profession, according to the RCN. The rise from
      4,821 in 1999 to 5,784 in 2002 was spelled out in the third of the college's
      annual labour market reviews, More Nurses, Working Differently, published last
      month.

PMID- 27718840
TI  - Webscan.

PMID- 27718839
TI  - Vantage point.
AB  - What do acute nurses know about community nursing? The answer is: 'Probably not
      enough'. The drive to improve access to acute care has meant that we are driving
      down lengths of stay in hospital, avoiding admission where possible and
      discharging patients much earlier than we used to.

PMID- 27718841
TI  - The first professional.
AB  - FLORENCE NIGHTINGALE (1820-1910) is known as a major founder of the modern
      nursing profession, and an expert on hospitals and public health. Some attention
      has been paid to her work in applied statistics but little to her expertise in
      methodology, philosophy, theology, social reform and militarism, or her extensive
      writings on India and more than modest commentaries on women's issues.

PMID- 27718842
TI  - Nurse nurse.

PMID- 27718849
TI  - Qualitative Research David Silverman Qualitative Research Sage Publications
      L26.99 464pp 9781849204170 1849204179 [Formula: see text].
AB  - DAVID SILVERMAN'S latest book builds on previous editions to provide up-to-date
      development in qualitative research and offers an overview of theoretical and
      practical considerations. Unlike many other qualitative research methodology
      books there is an emphasis on the function of qualitative research to articulate
      meaning.

PMID- 27718848
TI  - Leading by example.
AB  - There is a new face leading nursing and midwifery in Scotland: chief nursing
      officer (CNO) Paul Martin. As successor to Annie Jarvie, who retired in September
      after 12 years in post, he wants the profession's leaders to ensure that nurses
      and midwives remain at the heart of NHS modernisation.

PMID- 27718850
TI  - Diary.
AB  - Our roundup of what's on.

PMID- 27718852
TI  - Persistence brings success.
AB  - PROFESSOR CHRISTI Deaton leads the cardiovascular disease and diabetes research
      team at the school of nursing, midwifery and social work at the University of
      Manchester. She also teaches and supervises MPhil/PhD students. At the Central
      Manchester NHS Foundation Trust, professor Deaton is helping to implement the
      nursing, midwifery and allied health professionals research strategy and build
      research capacity and capability. Professor Deaton is also past chair of the
      council of cardiovascular nursing and allied health professionals of the European
      Society of Cardiology (ESC) and is engaged in the work of the ESC. She serves on
      the ESC congress planning committee, clinical practice guidelines committee and
      is invited to the ESC board meetings 2010- 2012 as a representative for nursing
      and allied health professions.

PMID- 27718854
TI  - Striving for improvement.
AB  - Since I joined Nurse Researcher as editor in 2008, the journal has undergone
      significant changes, some more obvious than others. Most noticeably it has moved
      to a larger format, bringing the journal in line with RCN Publishing's other
      specialist titles. The smaller format had been used since Nurse Researcher was
      first published in 1993, but the new size has brought a fresh approach to page
      design and has been well received by readers.

PMID- 27718847
TI  - Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.
AB  - BACKGROUND: Pembrolizumab is a humanized monoclonal antibody against programmed
      death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer
      (NSCLC), with increased activity in tumors that express programmed death ligand 1
      (PD-L1). METHODS: In this open-label, phase 3 trial, we randomly assigned 305
      patients who had previously untreated advanced NSCLC with PD-L1 expression on at
      least 50% of tumor cells and no sensitizing mutation of the epidermal growth
      factor receptor gene or translocation of the anaplastic lymphoma kinase gene to
      receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the
      investigator's choice of platinum-based chemotherapy. Crossover from the
      chemotherapy group to the pembrolizumab group was permitted in the event of
      disease progression. The primary end point, progression-free survival, was
      assessed by means of blinded, independent, central radiologic review. Secondary
      end points were overall survival, objective response rate, and safety. RESULTS:
      Median progression-free survival was 10.3 months (95% confidence interval [CI],
      6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to
      6.2) in the chemotherapy group (hazard ratio for disease progression or death,
      0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6
      months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy
      group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response
      rate was higher in the pembrolizumab group than in the chemotherapy group (44.8%
      vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+
      to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related
      adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of
      patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs.
      53.3%). CONCLUSIONS: In patients with advanced NSCLC and PD-L1 expression on at
      least 50% of tumor cells, pembrolizumab was associated with significantly longer
      progression-free and overall survival and with fewer adverse events than was
      platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov
      number, NCT02142738 .).

PMID- 27718858
TI  - Resources.

PMID- 27718859
TI  - 'Free' nursing care.
AB  - Throughout the past year nurses across the UK have been involved in implementing
      many changes relating to the provision and management of health care. Some have
      been made to improve specific local situations, but most have been necessary to
      meet the government's agenda to modernise healthcare provision.

PMID- 27718860
TI  - Conferences.

PMID- 27718861
TI  - Award deadline nears.
AB  - Nurse managers have until February 15 to submit applications for a European
      Health Management Association (EHMA) award worth US$5,000.

PMID- 27718862
TI  - Survey on support staff.
AB  - Up to 200 managers of children's services are to be surveyed on the role of
      support workers by the RCN paediatric nurse managers forum.

PMID- 27718863
TI  - Webscan.
AB  - Government proposals for establishing foundation trusts have been the subject of
      intense scrutiny and dissent in recent months, writes Steven Black.

PMID- 27718864
TI  - The fact that some of the most critical matters in Agenda for change were being
      resolved only in january with implementation expected from april is, in
      management speak, 'unhelpful'.
AB  - A group of senior nurses were sitting together recently discussing what will face
      nurses in 2003. Not surprisingly, the Agenda for Change pay modernisation
      proposals soon dominated the conversation. Uncertainties about implementation
      were a major concern, and there is frustration that the talks have gone on for so
      long with so many issues still to be addressed. The fact that some of the most
      critical matters were being resolved only in January with implementation expected
      from April is, in management speak, 'unhelpful'.

PMID- 27718865
TI  - Nurse nurse.

PMID- 27718866
TI  - Nurse managers set for national pay deal.
AB  - More than nine out of ten NHS nurse managers will come under the national Agenda
      for Change pay scheme, it emerged last month.

PMID- 27718867
TI  - Top job for NM adviser.
AB  - Martin Bradley (pictured below) is with- drawing as a member of the Nursing
      Management editorial advisory board following his appointment as RCN Northern
      Ireland board secretary.

PMID- 27718869
TI  - New year honours.
AB  - Jenifer Wilson-Barnett, professor of nursing and head of the Florence Nightingale
      school of nursing at King's College London (pictured right), headed the list of
      nurses granted new year honours. She was made a dame.

PMID- 27718870
TI  - Nursing in care homes Nazarko Linda Nursing in care homes Blackwell Publishing
      400pp L19.99 0 632 05226 0 0632052260 [Formula: see text].
AB  - For me, the most user friendly book I have read this month is Nursing in Care
      Homes by Linda Nazarko. This book is probably as useful to those nurses in
      primary care trusts, who are working increasingly with nursing home nurses, as it
      is for nursing home nurses themselves.

PMID- 27718872
TI  - Welsh roll out for management training.
AB  - The RCN announced last month that it is rolling out its clinical leadership
      programme to seven trusts across Wales.

PMID- 27718873
TI  - Leadership programme benefits confirmed.
AB  - Research has provided further evidence that the RCN clinical leadership programme
      benefits nurse managers in terms of leadership capability.

PMID- 27718874
TI  - It's a sex thing!
AB  - Early findings from a survey of nurses undergoing Leading Empowered Organisation
      (LEO) training have revealed differences between how men and women approach the
      issue of leadership.

PMID- 27718875
TI  - Divide and Conquer to Treat Lung Cancer.

PMID- 27718876
TI  - Fighting for a faculty.
AB  - Christmas is approaching and, just as last Christmas seems as if it were only
      yesterday, the same goes for the RCN's forums which have again been meeting to
      plan their strategies for the next financial year.

PMID- 27718877
TI  - Using reflective writing to gain insight into practice with older people.
AB  - Much has been written about reflection and its potential to develop not only
      practitioners but an understanding of nursing practice and therapeutic working
      through theory that is embedded in practice ( Benner 1984 , Rolfe 1998 , 1996 ,
      Schon 1991 ). A key skill needed by nurses is the ability to work in partnership
      with older people. To achieve this, it is important for nurses to be able to
      'make sense' of their practice, and to understand their contribution in
      therapeutic working. Structured reflection can therefore be a tool to help nurses
      gain a greater insight not only into professional practice but into their working
      relationship with older people.

PMID- 27718878
TI  - Blooming marvellous?
AB  - Intermediate care is a key government priority and local services are developing
      at a rapid pace. But while many frontline staff will probably support the values
      and ethos of intermediate care, they will also be aware of the tensions and
      difficulties which this way of working can raise.

PMID- 27718879
TI  - ?
AB  - Residents from four nursing homes were recruited for this study of the effects of
      three interventions upon agitated behaviour. A four-group, repeated measures
      experimental design was devised, and a modified version of the Cohen-Mansfield
      Agitation Inventory was used to record the behavioural responses. The subjects
      were exposed to calming music (Pachelbel's Canon in D), hand massage (following a
      research-based protocol), a combination of the two, or no intervention (the
      control group). Each of the interventions reduced agitation more than the
      control, and this benefit was sustained. No additional benefit was shown from
      combining calming music with simultaneous hand massage.

PMID- 27718881
TI  - Third-Party Confidences: The Uses of Information in a Psychoanalytic Institute.

PMID- 27718880
TI  - Non-conscious processes and dual-process theories in health psychology.

PMID- 27718886
TI  - The Structure and Technique of Community Meetings: The Short-term Unit.

PMID- 27718882
TI  - The Ambiguity of Confidentiality in a Psychoanalytic Institute.

PMID- 27718887
TI  - "The Action Level"(r).

PMID- 27718888
TI  - Platelet-rich plasma for tissue regeneration can be stored at room temperature
      for at least five days.
AB  - BACKGROUND: Autologous platelet-rich plasma (PRP) is gaining increasing use as a
      wound healing promoter in a variety of clinical settings, including dentistry.
      Fresh PRP is often used, necessitating daily draws. The present study
      investigates the possibility of using stored PRP without having to freeze it by
      storing PRP under variable conditions and assessing growth factor release as a
      surrogate marker of continued viability. METHODS: Freshly drawn PRP was stored in
      oxygen permeable and non-oxygen permeable containers under conditions of constant
      agitation with or without added prostaglandin, intermittent agitation and no
      agitation, over an 8-day period. Serial platelet counts, mean platelet volume,
      platelet distribution width and platelet-large cell ratio, and collagen-induced
      aggregometry were undertaken. Once collagen-induced aggregation had gone to
      completion, the plasma was centrifuged to pellet platelet material and the
      supernatants separated and frozen for batched analysis of released platelet
      derived growth factor-BB (PDGF-BB). RESULTS: As would be anticipated, platelet
      counts, percentage aggregation and PDGF-BB levels all reduced over time. Platelet
      parameters suggested that platelets were more stable in the non-oxygen permeable
      containers, possibly due to pH drift and a degree of microaggregate formation in
      the oxygen permeable containers. CONCLUSION: Although platelet integrity and PDGF
      BB fell over time, the intermittently agitated non-oxygen permeable container
      appeared to retain better platelet integrity and function, and PDGF-BB release,
      than other storage conditions, with potential for clinical use for 5-8 days.

PMID- 27718889
TI  - Masculinities on transnational journeys: sexual practices and risk management
      among male Chinese immigrants to Canada.
AB  - Recent critical studies of men and masculinities have encouraged greater
      consideration of global, international and transnational perspectives and
      processes. Drawing on interview data from a larger research study of
      transnationalism and HIV risk through the experiences of recent male Chinese
      immigrants to Canada, this article examines the intersection of masculinity,
      sexual practice and the HIV risk in a transnational context. As a gendered
      strategy, transnational mobility is not only employed by men to cope with the
      challenges of masculinity enactment encountered in Canada, but also to facilitate
      sexual activities back in China. By highlighting particular risk factors arising
      from transnational spaces these men inhabit, the paper reveals the interactive
      and interconnected effects that such experiences have on Chinese immigrant men's
      particular behavioural patterns associated with HIV risk, as well as their
      capacity to respond to this risk.

PMID- 27718891
TI  - Erythropoietin reduces white matter damage in two-day-old rats exposed to
      hypoxic/ischemia injury.
AB  - OBJECTIVE: The aim of the study was to investigate whether erythropoietin (EPO)
      could protect against white matter damage (WMD) in a preterm equivalent neonatal
      rat hypoxic-ischemia (HI) model. METHODS: 113 two-day-old male rat pups were
      divided randomly into three groups: sham-treated, bilateral carotid artery
      occlusion (BCAO)-treated, BCAO + EPO-treated group. EPO (50 U/10 g body weight)
      or saline alone was administered intraperitoneally immediately after BCAO
      surgery. Body weight, brain weight, brain water content, and expression of myelin
      basic protein (MBP) were assessed at day 1, 3, 7, and 14 after HI insult. Morris
      water-maze (MWM) test was used to assess neurological behavior from day 31 to 35
      after HI insult. RESULTS: Body weights of BCAO + EPO group were greater than
      those of BCAO group rats (P < 0.05). Specifically, at day 3 and 7 after HI, brain
      weights of BCAO + EPO-treated rats were higher than BCAO-treated animals (P <
      0.05); at day 7 and 14 after HI, MBP of BCAO + EPO-treated rats were higher than
      BCAO-treated animals (P < 0.05). Similarly, the brain water content at day 3
      after HI in BCAO + EPO-treated rats was lower than BCAO-treated animals (P <
      0.05). The body weight, brain weight, brain water content, and MBP expression in
      BCAO + EPO-treated group were comparable to those in the sham-treated group.
      Spatial learning and memory of BCAO + EPO-treated rats was significantly improved
      over the BCAO-treated group and was comparable to the sham-operated animals.
      CONCLUSION: EPO treatment could be a potential intervention in treating WMD for
      preterm infants.

PMID- 27718890
TI  - Benefits from an autobiographical memory facilitation programme in relapsing
      remitting multiple sclerosis patients: a clinical and neuroimaging study.
AB  - While the efficacy of mental visual imagery (MVI) to alleviate autobiographical
      memory (AM) impairment in multiple sclerosis (MS) patients has been documented,
      nothing is known about the brain changes sustaining that improvement. To explore
      this issue, 20 relapsing-remitting MS patients showing AM impairment were
      randomly assigned to two groups, experimental (n = 10), who underwent the MVI
      programme, and control (n = 10), who followed a sham verbal programme. Besides
      the stringent AM assessment, the patients underwent structural and functional MRI
      sessions, consisting in retrieving personal memories, within a pre-/post
      facilitation study design. Only the experimental group showed a significant AM
      improvement in post-facilitation, accompanied by changes in brain activation
      (medial and lateral frontal regions), functional connectivity (posterior brain
      regions), and grey matter volume (parahippocampal gyrus). Minor activations and
      functional connectivity changes were observed in the control group. The MVI
      programme improved AM in MS patients leading to functional and structural changes
      reflecting (1) an increase reliance on brain regions sustaining a self
      referential process; (2) a decrease of those reflecting an effortful research
      process; and (3) better use of neural resources in brain regions sustaining MVI.
      Functional changes reported in the control group likely reflected ineffective
      attempts to use the sham strategy in AM.

PMID- 27718892
TI  - Cephalometric risk factors of obstructive sleep apnea.
AB  - INTRODUCTION: Previous studies on risk factors of obstructive sleep apnea (OSA)
      are highly controversial and mostly identifying a few cephalometric risk factors.
      METHODS: OSA diagnosis was made according to the patients' apnea-hypopnea index
      (AHI). Included were 74 OSA patients (AHI > 10) and 52 control subjects (AHI <=
      10 + free of other OSA symptoms). In both groups, 18 cephalometric parameters
      were traced (SNA, SNB, ANB, the soft palate's length (PNS-P), inferior airway
      space, the distance from the mandibular plane to the hyoid (MP-H), lengths of
      mandible (Go-Gn) and maxilla (PNS-ANS), vertical height of airway (VAL), vertical
      height of the posterior maxilla (S-PNS), superior posterior airway space (SPAS),
      middle airway space, distances from hyoid to third cervical vertebra and
      retrognathion (HH1), C3 (C3H), and RGN (HRGN), the maximum thickness of soft
      palate (MPT), tongue length (TGL), and the maximum height of tongue). These
      parameters were compared using t-test. RESULTS: Significant variables were SPAS
      (p = 0.027), MPT, TGL, HH1, C3H, HRGN, PNS-P, S-PNS, MP-H, VAL, and Go-Gn (all p
      values <= 0.006). CONCLUSION: OSA patients exhibited thicker and longer soft
      palates, hyoid bones more distant from the vertebrae, retrognathion, and
      mandibular plane, higher posterior maxillae, longer mandibles, and smaller
      superior-posterior airways.

PMID- 27718894
TI  - Events.

PMID- 27718893
TI  - Website watch.
AB  - This month's article by Philip Woodrow on assessing blood pressure in older
      people (p29) makes clear the scale of hypertension among those in middle and
      later life - almost a third of people over 50 are hypertensive. While this site
      is not geared specifically towards older people or those who care for them,
      nurses working in the field will find plenty of the information it contains
      useful and relevant to their practice.

PMID- 27718895
TI  - ?
AB  - It is likely that a good standard of care in a nursing home will result from
      effective teamworking, but little research in this area has been carried out.
      This study employed focus group methodology to explore the perceptions of staff
      working in nursing homes in southern England. All the nurses in the sample
      described themselves as members of a team. Good communication was stressed as
      being crucial for effective teamworking, but the hierarchical nature of the teams
      they described sometimes impeded rather than promoted communication.

PMID- 27718896
TI  - Challenges in conducting research with acutely ill hospitalized older patients.
AB  - Older people are major users of acute hospital services, yet the research
      evidence devoted to issues which affect them does not reflect this situation. In
      this Australian paper, the authors reflect upon the issues raised by a study they
      undertook in an acute ward setting. This project used a questionnaire with Likert
      type scales, followed by open-ended questions, in order to explore perceptions of
      the relative importance of various aspects of nursing care. Issues encountered
      when the questionnaire was administered included fatigue, visual impairment and
      hearing difficulties. The authors stress that many of the problems they had to
      overcome reflected the changing nature of acute care, rather than the age of the
      subjects. Intensive treatment regimes and the constant pressure to achieve early
      discharge have both had a major impact on the opportunities a researcher may have
      to interview subjects.

PMID- 27718897
TI  - ?
AB  - This qualitative study was carried out in one practice in a socially deprived
      district of inner-city Manchester. Patients' personal accounts of the factors
      which caused them to accept or reject the offer of vaccination were studied in
      order to detect common influences. The three most important factors were
      identified as trust or mistrust in modern medicine, prior experience of
      vaccination, and the perceived risk from influenza. Current health promotion
      initiatives encouraging influenza vaccination were largely regarded in a negative
      light. The authors suggest that future campaigns should place vaccination in a
      wider context of health maintenance.

PMID- 27718898
TI  - Taking control of cancer Taking control of cancer Molen Beverley van der Class
      Publishing 170pp L17.99 1 85959 091 8 1859590918 [Formula: see text].
AB  - This publication is principally for those affected by cancer and its treatment,
      although the patient stories that lie at its heart provide insights for patients
      and healthcare professionals alike.

PMID- 27718900
TI  - Nutrition scandals hit the headlines - again.
AB  - The subject of nutrition for older people in acute care has arisen again in a
      particularly distressing manner. According to newspaper reports ( Rogers 2004 ,
      Warrington 2004 ), a coroner is demanding a public inquiry into claims that
      hospital patients aged 65 to 93 were deliberately starved to death. He believes
      that this could be Britain's first case of forced 'mass euthanasia'.

PMID- 27718901
TI  - Home owners fined over rail risk assessment.
AB  - The owners of a residential home in Staffordshire have been fined L20,000 for
      failing to carry out an assessment of the risks of using bed rails. The case came
      to court after a resident slipped under the wrongly fitted rails on a new bed and
      was asphyxiated.

PMID- 27718902
TI  - ?
AB  - At the 25th anniversary celebrations of the Alzheimer's Society Anne Robinson
      (pictured right with her husband John Penrose and vice chairman of the society
      Irene Kerr) promised to donate L1 to the society every time she's rude to a
      contestant on the TV show she hosts, The Weakest Link.

PMID- 27718903
TI  - 'Time famine' means people are 'too busy to care'.
AB  - Many older people will have to care for themselves if current confusion about
      responsibility for caring is not resolved, according to recent research.

PMID- 27718904
TI  - Costs of caring spiral in wales as older people increase in numbers.
AB  - The number of older people in Wales is set to rise dramatically over the next 20
      years, according to population projections released by the Welsh Assembly
      Government.

PMID- 27718905
TI  - NSF has helped change ageist attitudes in health care, 'tsar' for older people
      claims.
AB  - The National Service Framework for Older People (NSF) has changed the culture of
      the NHS and has a bigger 'reach' than any other health framework, the
      government's older people's 'tsar' has said.

PMID- 27718906
TI  - Client profiles in nursing: Adult and the Elderly 2 Sam Parboteeah Client
      profiles in nursing: Adult and the Elderly 2 and Penny Tremayne Greenwich Medical
      228pp L18 1 84110 150 8 1841101508 [Formula: see text].
AB  - This innovative series provides client profiles with related questions to
      encourage the reader to explore underlying issues. The editors suggest the reader
      should use the profiles to help link theory to practice and to reflect on his or
      her own care giving.

PMID- 27718907
TI  - New websites.

PMID- 27718908
TI  - Diabetes for nurses Lynne Jerreat Diabetes for nurses Whurr Publishing pp282
      second edition L25 186156 295 0 1861562950 [Formula: see text].
AB  - This is a comprehensive and up-to-date diabetes textbook written by a nurse for
      nurses. It is easy to read and is divided into three clear sections. The first
      takes a pathophysiological view of diabetes, discusses treatments available and
      examines the complications of the disease. Patient education and patient
      management regimes are discussed in the second section and finally broader issues
      are examined including the psychological and ethical aspects of diabetes. This is
      particularly refreshing, as this book places a significant emphasis upon the
      psychosocial aspects of diabetes rather than focusing purely on the biomedical
      aspects of the disease.

PMID- 27718909
TI  - Research recruitment.

PMID- 27718910
TI  - Networks.

PMID- 27718911
TI  - 'Sam's bill' could bring benefits for carers.
AB  - A private member's bill designed to improve the rights of carers has passed to
      the committee stage of the House of Commons, where it will be examined in detail
      by MPs.

PMID- 27718916
TI  - Have your say.
AB  - Scotland has a bad reputation when it comes to healthy eating and exercise, with
      the Scottish Executive (SE) suggesting that more than half a million Scots have
      coronary heart disease.

PMID- 27718913
TI  - Parkinson's nurses can help save money, PDS says.
AB  - Next month's Parkinson's Disease Awareness Week will focus on the work of nurse
      specialists and how they can provide a vital link between health and social care
      at local level.

PMID- 27718917
TI  - Under cover.
AB  - Have you ever wished for a text on leadership that makes you smile as well as
      think, that you can read at bedtime without being kept awake pondering your own
      and others' inadequacies, and that cuts through jargon to tell you what you need
      to function usefully in a leadership role?

PMID- 27718918
TI  - Prem singh.
AB  - What gets you out of bed in the morning? A profound belief in the quest to tackle
      inequalities in health care. While we can be proud of the improvements we have
      made in healthcare provision in this country, there remain significant gaps and
      variances in out-comes. We have much more to do.

PMID- 27718919
TI  - Mixed reaction from senior nurses to plans for new PCTs.
AB  - Senior nurses have given a mixed reaction to the long awaited Department of
      Health announcement last month on the future configuration of primary care
      organisations.

PMID- 27718920
TI  - New look.
AB  - Two major health related websites have been given new looks. The National
      Institute for Health and Clinical Excellence (NICE), at www.nice.org.uk , has
      simplified its site so that both its public health and clinical excellence areas
      can be accessed from its home page. Comments on draft NICE guidance and
      suggestions for topics for future guidance can be made under its 'get involved'
      section.

PMID- 27718921
TI  - Bed numbers fall.
AB  - The number of hospital beds has fallen by a third in the past 20 years, yet the
      NHS does more work than ever before, according to the NHS Confederation.

PMID- 27718923
TI  - ?
AB  - Full honours: nursing director at Surrey and Sussex Healthcare NHS Trust Irene
      Scott (pictured centre) carried Nightingale's lamp last month at the annual
      commemoration of Florence Nightingale's birthday. She was joined at Westminster
      Abbey by Florence Nightingale scholars Vivienne Davies-Quarrell, director of
      service development at Memory Matters, a support group in north Wales for young
      people with dementia, and Tom Fernandez, a charge nurse at the Ian Charleson day
      centre for people with HIV /AIDS, at The Royal Free Hospital, London. Around
      2,000 nurses and nursing leaders attended the service, at which Archbishop of
      Canterbury Rowan Williams said: 'A professionalism that does not include the
      skills of serving human dignity is no professionalism at all'.

PMID- 27718922
TI  - District nurses 'lack leadership', says QNI.
AB  - A lack of professional leadership has left the district nursing workforce without
      an effective voice in policy making and planning, according to a report from the
      Queen's Nursing Institute (QNI).

PMID- 27718924
TI  - Bullying.
AB  - What's the difference between firm but fair management on the one hand, and
      bullying and harassment on the other? This is one of the questions that NHS
      Employers considers in its latest guidance.

PMID- 27718925
TI  - Guidelines needed.
AB  - Nurse prescribers are being prevented from using their full prescribing powers
      because NHS trust managers have allegedly failed to draw up essential guidelines.

PMID- 27718926
TI  - Infections.
AB  - For the latest news on healthcare associated infections (HAIs) in Wales, visit
      the new Welsh Healthcare Associated Infection Programme (WHAIP) website at
      www.wales.nhs.uk/sites/home.cfm?OrgID=379.

PMID- 27718927
TI  - Leaders wanted.
AB  - Senior nurses and other healthcare professionals have been invited to apply for
      the leadership fellow award scheme run by The Health Foundation.

PMID- 27718928
TI  - Rewarding efficiency.
AB  - SINCE THE new year, and for the first time in the history of the NHS, all
      eligible patients across England have the right to exercise choice over where and
      when they receive hospital treatment. They can now choose services that meet
      their individual needs and preferences.

PMID- 27718929
TI  - Get connected.
AB  - WHEN WAS the last time you wrote a cheque? Or withdrew money over the counter at
      a bank? Some time ago, I expect.

PMID- 27718930
TI  - Change at the top.
AB  - The government reshuffle last month has brought new faces to the Department of
      Health.

PMID- 27718931
TI  - ?
AB  - MAJOR HEALTH reforms are currently sweeping through the NHS and they are all
      good, both for patients and nurses. But they offer the nursing profession
      challenges and opportunities.

PMID- 27718932
TI  - Nurse prescribing.
AB  - On May 1, the entire British National Formulary, apart from a few controlled
      drugs, was opened up to nurse prescribers. At the same time, the Nursing and
      Midwifery Council published its revised and updated Standards of Proficiency for
      Nurse and Midwifery Prescribers.

PMID- 27718933
TI  - Mental health.
AB  - Chief nursing officer for England Chris Beasley has completed her review of
      mental health nursing and published the recommendations at
      www.dh.gov.uk/assetRoot/04/13/38/40/04133840.pdf writes Ruth Williams.

PMID- 27718934
TI  - Conferences.

PMID- 27718935
TI  - Taking the initiative: nurse intrapreneurs in the NHS.
AB  - ENTREPRENEURSHIP HAS traditionally been associated with individuals operating in
      the private sector. However, there is increasing evidence to suggest that
      entrepreneurs have a role in public sector organisations, especially as
      governments encourage these to become more market oriented ( Ennew et al 1998 ).

PMID- 27718936
TI  - Conferences.

PMID- 27718937
TI  - Have your say.
AB  - How relevant to your work is the creation of a strategy for mental health for the
      European Union (EU)? If you are interested in mental health in a European
      context, then read the European Commission (EC) green paper, Promoting the Mental
      Health of the Population: Towards a strategy on mental health for the European
      Union.

PMID- 27718938
TI  - Trust ratings.
AB  - NHS trusts will from this year be judged by how they use resources as well as by
      the standards of care they provide.

PMID- 27718939
TI  - Changes at NDA.
AB  - The Nurse Directors Association will no longer have a chief executive, it was
      announced last month as Liz Fradd stepped down.

PMID- 27718940
TI  - Warning over staff shortage as jobs cut.
AB  - Laying off staff immediately to save money will mean job shortages by the end of
      the decade, nursing leaders have been warned.

PMID- 27718941
TI  - Safe staffing.
AB  - 'Safe staffing saves lives' is the theme next month of International Nurses' Day,
      held annually on Florence Nightingale's birthday, May 12.

PMID- 27718942
TI  - Vantage point.
AB  - WHILE WAITING outside an office recently, I was drawn to numerous copies of a
      healthcare management journal.

PMID- 27718943
TI  - ?
AB  - Food for thought: the National Institute for Health and Clinical Excellence
      (NICE) and the National Collaborating Centre for Acute Care have launched a
      clinical guideline to help NHS staff identify patients who are malnourished or at
      risk of malnutrition. It recommends that all hospital inpatients on admission and
      outpatients at their first clinic appointments are screened, and spells out when
      nutrition support should be considered. The guideline also suggests that all
      healthcare professionals who are directly involved in patient care should receive
      education and training, relevant to their post, on the importance of providing
      adequate nutrition, and that each acute hospital trust should employ at least one
      specialist nutrition support nurse and establish a nutrition steering committee.

PMID- 27718944
TI  - Ex-CNO highlights areas for improvement.
AB  - Former chief nursing officer (CNO) Anne Jarvie (below) has highlighted five areas
      of care provision that need to be improved across Scotland, after an inquiry into
      events at NHS Lothian.

PMID- 27718945
TI  - Piecing together the whole pictureSue Ryder Care is a voluntary provider of care
      that has implemented the Agenda for Change pay modernisation initiative across
      its services. Dan Beety explains why.
AB  - The recent switch to a patient led healthcare service in the UK offers both
      challenges and opportunities for voluntary care providers. They are now able to
      work more closely than ever with the statutory health and social care sectors
      while remaining sufficiently independent to offer innovative and responsive
      services to their local communities.

PMID- 27718946
TI  - Local problems.
AB  - Healthcare staff are often less concerned with global issues such as avian flu
      than with local problems, and these can be addressed with the help of Public
      Concern at Work (PCaW), an independent authority on public interest
      whistleblowing.

PMID- 27718947
TI  - Service delivery.
AB  - A new company, Dr Foster Intelligence, has been launched to help NHS and social
      care managers deliver services efficiently and in a way that responds to the
      needs of users.

PMID- 27718948
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27718949
TI  - 'Bird flu'.
AB  - Although H5N1 remains a flu virus that affects mostly birds, and all human cases
      so far have followed close contact with infected birds, there is concern, and
      some confusion, among the public about the difference between avian and pandemic
      flu.

PMID- 27718950
TI  - Under cover.
AB  - There is much that nursing and other healthcare leaders can learn from Jack
      Welch, or 'Neutron Jack' as he has come to be known.

PMID- 27718951
TI  - Sexual orientation.
AB  - The 2004 Civil Partnership Act, which came into effect last December, means that
      many NHS and social care organisations will need to review their policies,
      procedures and practices for staff, as well as patients, so they are inclusive in
      language and context, writes Ruth Williams.

PMID- 27718953
TI  - Essence of care.
AB  - The Department of Health has launched a new Essence of Care benchmark, on health
      promotion.

PMID- 27718952
TI  - Acting the part.

PMID- 27718954
TI  - Editorial.
AB  - PROVIDING CARE is fundamental to nursing and, for me, must involve the complete
      and personal care of each human being. Some claim that we have forgotten this
      and, in many places, I think we have. But, in experiencing the death of my father
      last month, I have been privileged to see the provision of care at its best, both
      in the NHS and in the hospice movement.

PMID- 27718955
TI  - Worth a packet?
AB  - UP TO one in five nursing directors are after their chief executives' jobs,
      latest annual survey results from workforce analysts NHS Partners suggest.

PMID- 27718956
TI  - The evidence speaks for itself ... but can the public?
AB  - TODAY'S PATIENTS take their lives in their hands. With health information, good
      or bad, now more available than ever, many people approach their health care in
      the way they would any other purchase. They shop around, looking for best 'value'
      and the benefits accrued by making the right choice.

PMID- 27718957
TI  - New careers microsite.
AB  - Following the recent launch of NHS Career's microsite, another that will be of
      interest to nurse leaders has appeared, writes Steven Black.

PMID- 27718958
TI  - ?
AB  - Leading edge: Chris Beasley, England's new chief nurse, at the annual CNO
      conference in Manchester last month. NHS chief executive Sir Nigel Crisp
      testified to her 'courage, spirit and common sense', and described her as a 'team
      player' who 'talks straight'.

PMID- 27718959
TI  - Tackling infections.
AB  - As the new chief nursing officer (CNO) for England starts work in her new role,
      the Department of Health website describes how she and the health service's
      cohort of modern matrons will tackle healthcare acquired infections.

PMID- 27718961
TI  - Department of Health sets target on healthcare acquired infections.
AB  - Health secretary John Reid used his speech at the conference to announce the
      latest government measure to tackle healthcare acquired infections.

PMID- 27718962
TI  - 'Blogging' nurses.
AB  - 'Blogging' is too new a term to be included in the latest Oxford English
      Dictionary but it is rapidly becoming an influential way of having your say.
      Blogs are weblogs, or regularly updated webpages in diary form, often with
      commentaries on, and links to, other websites.

PMID- 27718960
TI  - Urged to put care on top agenda.
AB  - On the issue of quality of patient care, Professor Beasley is considering the
      introduction of 'mystery shoppers' to carry out anonymous inspections of
      hospitals, but stressed that they would not be used without consulting staff.

PMID- 27718963
TI  - Messages from the conference platform.
AB  - NHS chief executive Sir Nigel Crisp faced renewed calls for greater action on
      modernising pay through Agenda for Change in general practice.

PMID- 27718964
TI  - Editorial.
AB  - Great expectations! That's what I came away with this year from the English chief
      nursing officer's (CNO) annual conference.

PMID- 27718965
TI  - Nursing leaders.
AB  - Establishing the issue of care on the most senior NHS agendas is among the most
      important tasks for nurses, according to the new chief nursing officer (CNO) for
      England.

PMID- 27718967
TI  - Critical faculties.
AB  - NURSE CHRIS SMITH made a unique move this year when he became critical care lead
      for the Southampton University Hospitals NHS Trust.

PMID- 27718966
TI  - Public health white paper spells out long-term disease management role of
      community matrons.
AB  - Ministers have spelled out their plans to make community based senior nurses
      central to delivering their public health agenda.

PMID- 27718968
TI  - NHS Employers.
AB  - If you are unfamiliar with NHS Employers and its aims, comprehensive information
      on the organisation is available on the NHS Confederation website,
      www.nhsconfed.org/ourpriorities/employers_organisation.asp.

PMID- 27718969
TI  - Managing complaints.
AB  - The NHSU meanwhile has launched a course to help complaints management staff
      adopt a more consistent approach to investigating and reporting complaints about
      the NHS.

PMID- 27718970
TI  - Salma ali.
AB  - I am responsible for the professional development of nursing in a primary care
      environment.

PMID- 27718971
TI  - Reviewing development.
AB  - Also available on the NHSU site is a new 'personal development review' toolkit
      (Gateway reference 4004).

PMID- 27718972
TI  - Mental health.
AB  - Mental Nurse is billed as 'the internet resource for UK mental health nurses' and
      offers a range of information on all things connected to mental health.

PMID- 27718973
TI  - Nurse nurse.

PMID- 27718974
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27718975
TI  - Vantage point.
AB  - ANOTHER ACADEMIC term has begun at our trust, bringing with it a new cohort of
      nursing and midwifery students. But larger cohorts and different types of student
      require us to think in new ways about the practice component of training.

PMID- 27718976
TI  - Who cares? one family's shocking story of 'care' in today's NHS Amanda Steane Who
      cares? one family's shocking story of 'care' in today's NHS.
AB  - EVERY YEAR, around 34,000 people die and around permanently due to clinical
      negligence in the NHS.

PMID- 27718977
TI  - A history of nursing through Philately Margaret B Ritchie A history of nursing
      through philately Teragram 64 L9.99 978-0955591501 0955591503 [Formula: see
      text].
AB  - Philately is described in Chambers Dictionary as the study of postage stamps.
      This can include the design, production and uses of stamps after they are
      authorised for issue usually by government authorities. Stamps can be issued to
      commemorate many different subjects and, as A History of Nursing Through
      Philately, shows, the nursing profession is foremost among them.

PMID- 27718978
TI  - National programme for IT 'delivers better care'.
AB  - The NHS National Programme for Information Technology is on course to deliver
      better care and L1.14 billion in savings by 2014, according to the government.

PMID- 27718980
TI  - Care for older patients.
AB  - Help the Aged has launched a series of guides to help hospital staff approach and
      care for older people correctly.

PMID- 27718979
TI  - Update for pre-employment checks.
AB  - NHS Employers has published an updated set of standards to help senior nurses and
      other staff to meet all the necessary requirements of pre-employment checks.

PMID- 27718981
TI  - Get connected.

PMID- 27718982
TI  - Engaging patients.
AB  - A new publication from Dr Foster Intelligence, called Patient Insight: Harnessing
      the power of public opinion, offers guidelines to help organisations maximise the
      value of information from, about and to patients, writes Ruth Williams.

PMID- 27718983
TI  - ?
AB  - Cut-throat competition: operations are being cancelled at the last minute due to
      the condition of surgical equipment being returned from outsourced
      decontamination services, theatre nurses have reported. Nurses have complained
      that surgical equipment has been returned late, with blood and bone clearly
      visible, and that instruments have been labelled off-site wrongly. A survey of
      around 8,500 theatre nurses by the Association for Perioperative Practice
      suggests that almost three quarters have had bad experiences associated with
      outsourced decontamination arrangements.

PMID- 27718984
TI  - Information technology.
AB  - The new Essential Information Technology Skills Programme (EITS) for NHS staff
      was launched last month by NHS Connecting for Health.

PMID- 27718986
TI  - Clinical governance.
AB  - Making clinical governance work well can be challenging.

PMID- 27718985
TI  - Have your say.
AB  - Health and social care in Northern Ireland is undergoing an ambitious programme
      of reform.

PMID- 27718988
TI  - Lean times ahead.
AB  - A NEW alliance of world experts in 'lean' health care has been established to
      help the NHS improve services.

PMID- 27718987
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27718989
TI  - Get connected.
AB  - New appointment WEAT NHS Connecting for Health (NHS CFH) are pleased to announce
      the appointment of Julie Tindale as national clinical lead for midwifery.

PMID- 27718990
TI  - ?
AB  - Speaking out: nurses rallied outside Derby Hospitals NHS Foundation Trust last
      month over proposals to downgrade staff. About 250 nurses on the trust's surgical
      wards face downgrading and could lose 20 per cent or more of their pay. They
      staged the rally in protest that the trust had not improved its offer for better
      pay protection. A spokesperson for the trust said it had been agreed that there
      would be a series of meetings for all Band 6 staff who might be affected by the
      proposed changes.

PMID- 27718993
TI  - Now we're cooking!
AB  - AT LAST year's annual RCN congress, the college launched Nutrition Now, a
      clinical campaign to raise standards of nutrition and hydration in hospitals and
      the community.

PMID- 27718991
TI  - Modern matrons are 'struggling to fulfil their role as leaders'.
AB  - Modern matrons are struggling to fulfil their leadership role, according to
      researchers at The University of Nottingham.

PMID- 27718996
TI  - New partnership 'good news' for hard of hearing.
AB  - High-street shops will offer NHS hearing tests and fit digital hearing aids in an
      attempt to reduce waiting times for patients.

PMID- 27718994
TI  - Conferences.
AB  - A Practical Guide to Proactively Managing and Improving Patient Safety on the
      Wards May 14 Manchester Conference Centre Further details: Healthcare Events.
      Tel: 020 8541 1399. Email: hannah@healthcare-events.co.uk Website: www.healthcare
      events.co.uk.

PMID- 27718997
TI  - Commissioners condemn care funding position.
AB  - The government's stance on providing nursing and personal care for nursing home
      residents has come in for criticism from members of the Royal Commission on Long
      Term Care, who have condemned ministers for their failure to implement
      recommendations made by the commission in 1999.

PMID- 27718998
TI  - ?
AB  - The views of members of minority ethnic groups concerning dementia services is an
      area of research in which findings remain relatively sparse. This study conducted
      in Scotland involved data collection from two sources. Semi-structured interviews
      were undertaken with service providers, including general practitioners and
      hospital consultants, community psychiatric nurses, and NHS and voluntary sector
      organisations providing mental health services for older people. The second
      aspect of the study involved four case studies of South Asian people who had a
      diagnosis of dementia. The results indicated that professionals had divided
      opinions on whether specialist services for people from ethnic minority groups
      should be developed. There was a wide measure of agreement that dementia should
      be discussed through the use of a 'physical illness' idiom. Service users focused
      on poor quality of life, and a desperate need for support.

PMID- 27719000
TI  - Letter to the editor.
AB  - Further to Hazel Heath's article 'Relative priorities' (NOP October), when some
      years ago my father, an active 84-year-old, was admitted to hospital, I visited
      him every other afternoon. We got into the habit of him having a bath before tea.
      Few people wanted one in the afternoon so Father could enjoy a long soak. I would
      run the bath and scrub his back as I had done at home.

PMID- 27718999
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27719001
TI  - Website watch.
AB  - caredirections.co.uk has 'no affiliation or association with any care provider'
      and as such manages to offer a wealth of seemingly independent information on
      subjects that many older people and their carers may have trouble unravelling.

PMID- 27719003
TI  - Deaths rise during summer heat - but winter kills more.
AB  - This year's hot summer may have killed more than 2,000 people, according to the
      Office for National Statistics (ONS).

PMID- 27719004
TI  - Unite - 'to endure and yet to dare'.
AB  - This is the time in the year when we unite to remember the people who made
      sacrifices so that the lives of future generations could be better than theirs.
      Those who made the ultimate sacrifice are commemorated in ceremonies, media
      coverage and, of course, in the remembrances of those who knew them.

PMID- 27719005
TI  - 'Intolerable' discharge delays must end, say MPs.
AB  - Too many older people are still waiting longer than is necessary to be discharged
      from hospital, according to MPs.

PMID- 27719006
TI  - Can we help persons with dementia find their way in a new environment?
AB  - There has been concern for many years that an older person with dementia is
      likely to experience increased disorientation if moved from one setting to
      another. A policy of rebuilding Canadian nursing homes and relocating their
      residents led these researchers to test a strategy for improving residents'
      ability to find their way in a new environment. A randomised controlled trial
      conducted in four nursing homes compared an intervention consisting of the use of
      a location map and a behavioural training technique called 'backward chaining'
      with a control group who did not receive it. 'Backward chaining' involved
      breaking the trip down into smaller sections which were rehearsed individually,
      with the section of the journey nearest the intended destination (the dining
      room) being learned first. The results indicated that residents in the treatment
      group demonstrated an increased ability to find their way to the dining room
      after one week, but that this effect was not maintained after three months.

PMID- 27719007
TI  - New publications.

PMID- 27719008
TI  - Handbook for Care Assistants: A Practical Guide to Working with Older
      People(Sixth edition) Handbook for Care Assistants: A Practical Guide to Working
      with Older People Lynne Phair and Sue Benson (editors) 180pp L14.95 1 87479 069 8
      1874790698 [Formula: see text].
AB  - The editors of this very valuable handbook have brought together acknowledged
      experts, each contributing to their own specialist area. The book is completely
      revised from a previous work and makes interesting and stimulating reading.
      Information is presented in an easily understandable, positive manner and is up
      to date in respect of good practice. All the chapters are important and cover
      topics dealing with every aspect of care of the older person.

PMID- 27719009
TI  - Managing parkinson's disease in long-term care.
AB  - I work in a nursing home for older people whose physical and psychological
      disabilities have come about because of the normal process of ageing. In some
      clients, however, the ageing process is hastened or complicated by other diseases
      such as Parkinson's disease (PD). Reading the CPD article has helped me to gain
      more knowledge of the nature of PD. Studying the article was an opportunity for
      me to reflect on and update my knowledge and understanding of the management of
      this condition. It has helped me to identify areas where I need to study further
      and improve my practice.

PMID- 27719010
TI  - ?
AB  - This clinical review brings together in an accessible format current findings on
      a common problem which does not receive the attention it deserves. The 'greying'
      of the world's population means that the absolute number of older people with
      alcohol use disorders is bound to increase. Primary, secondary and tertiary
      prevention strategies are discussed, and a useful list of relevant websites is
      provided.

PMID- 27719065
TI  - ?
AB  - This is an interesting, brief article about the legalities of making wills and
      the implications for those who become involved in the process.

PMID- 27719066
TI  - ?
AB  - This article draws on the author's experience of working in care homes,
      supporting staff and inspecting. It outlines five stages to consent in relation
      to older people in care homes and provides detailed explanations of these. It
      highlights pertinent current policy documents and explores the challenges of
      consent in long-term care, suggesting that consent is not a one-off episode
      requiring a consent form but is one stage in the continuum of service users'
      involvement in their care. It identifies legislative requirements and discusses
      consent by the service user or their representative.

PMID- 27719067
TI  - RCN says leadership programme will help develop older people's nursing.
AB  - A new leadership programme for nurses working with older people has been launched
      by the RCN, with funding from the Department of Health.

PMID- 27719068
TI  - Providing the best care.
AB  - Q What does your job entail? A My job title states that I am the matron of a 45
      bed nursing home. The term 'matron' is one that I have stuck to as older people
      relate more easily to it than they do to, say, 'nurse manager'. In reality, when
      you have your own business you must be able to turn your hand to a number of jobs
      and tasks. Joy, our deputy, takes a share of the nursing responsibility from my
      shoulders, but basically I am responsible, with my husband, for 45 patients, all
      their needs and for all our staff.

PMID- 27719072
TI  - Pneumonia jabs for over-65s.
AB  - Everyone aged 65 and over is to be offered immunisation against pneumococcal
      infection, the chief medical officer (CMO) has announced.

PMID- 27719069
TI  - Intermediate care: policy rhetoric or an effective strategy? A review of the
      literature.
AB  - The definition of intermediate care has broadened from a range of services
      designed to ease the transition from hospital to home, and from medical
      dependence to functional independence ( Manthorpe et al 2003 ). Steiner 1997 ),
      to encompass 'a range of integrated services to promote faster recovery from
      illness, prevent unnecessary acute hospital admission, support timely discharge
      and maximise independent living' ( DH 2002 ).The National Service Framework for
      Older People (NSF) ( DH 2001a ) defines it more explicitly: 'Older people will
      have access to a new range of services at home or in designated care settings, to
      promote their independence by providing enhanced services from the NHS and
      councils to prevent unnecessary hospital admission and effective rehabilitation
      services to enable early discharge from hospital and to prevent premature or
      unnecessary admission to long-term residential care.'

PMID- 27719073
TI  - Reject retirement age of 65.
AB  - As a nurse on the front line of ward work, mostly medicine and older people, I
      urge nurses to reject retirement at age 65.

PMID- 27719075
TI  - 'Absurd' funding of long-term care needs review, say MPs.
AB  - Urgent reform of the 'absurd' funding system for long-term care in England is
      required in order to ensure a fairer deal for older people, an influential
      parliamentary committee has said.

PMID- 27719074
TI  - Reminiscence to restore the soul.
AB  - Hymns are proving a popular means of unlocking the past for older people in
      Scotland. A reminiscence project run by a church community in Edinburgh has been
      so successful that it has culminated in the production of a CD of popular hymns
      sung by the choirs and members of three churches in Morningside, in the south of
      the city.

PMID- 27719076
TI  - A sideways look at images of age.
AB  - The Guardian reported that 'pensioners' in the Essex seaside resorts of Frinton
      and Clacton are being urged to fit cat bells to their purses and wallets so that
      they will know if someone is trying to steal their cash.

PMID- 27719078
TI  - Everyday actions shape future directions.
AB  - The need for older people, and all of us who work with them, to influence the
      future direction of policies and services offers no respite when the ballot boxes
      are sealed. In fact, it becomes more urgent as new and re-elected members of the
      UK's parliaments and assemblies assume their seats and plan their work.

PMID- 27719080
TI  - Care Directions.
AB  - This site is the internet's 'unique guide to care and the rights of older people
      in the UK'. Or so it claims. It is also an 'essential resource of daily living,
      health, nutrition, welfare, financial and legal matters', which makes it sound
      like a onestop shop for any older person in search of advice of any sort.

PMID- 27719083
TI  - Warnings of looming crisis in care homes continue.
AB  - Inadequate local authority fee rates are cited as the most common cause for care
      home closure, according to a research project funded by the Department of Health.

PMID- 27719084
TI  - We are the champions.
AB  - The Welsh Government Assembly has agreed to support the principle of free
      personal care in Wales. But the decision will make no difference to the lives of
      the thousands of people who could benefit because the assembly cannot produce the
      money to support its principles.

PMID- 27719086
TI  - Jubilee celebrations in london's east end.
AB  - Music, wartime food, a pearly king and queen and traditional bunting helped make
      a jubilee street party for older patients from London's East End hospitals go
      with a bang.

PMID- 27719085
TI  - The perils of partnership.
AB  - Partnership working is a key theme of social policy in the UK. Under New Labour
      there has been a greater recognition that many of the social issues we face are
      so complex that they require a co-ordinated response from a range of different
      people and agencies. This is not only true of verarching social problems such as
      rising crime, substance misuse and social exclusion, but also of particular
      service user groups (such as older people or those with mental health problems or
      learning difficulties) whose needs may span the boundaries of traditional
      services. To use the New Labour jargon, 'joined-up problems' require 'joined-up
      solutions'.

PMID- 27719087
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27719088
TI  - Inaction on mental incapacity prompts criticism.
AB  - The Westminster government has come under further criticism for failing to reform
      legislation to support people with mental incapacity, including dementia. Many
      nurses feel that recent Nursing and Midwifery Council guidance on covert
      administration of medicines would be much assisted by a sound legislative
      framework underpinning the rights of people with mental incapacity.

PMID- 27719089
TI  - Free personal care in wales 'impractical', says minister.
AB  - The introduction of free personal care in Wales is being blocked by lack of
      resources and the Welsh Assembly's lack of authority to pass the necessary
      legislation.

PMID- 27719090
TI  - Time is right for decisive action.
AB  - Warnings of a looming crisis in care home provision for older people are becoming
      increasingly alarming. Two new Department of Health-funded surveys report a
      closure rate of around 5 per cent of homes per year, the main reason being
      business failure due to inadequate local authority fee rates. Among the closures
      are many homes that offered good quality care (see page 5 ).

PMID- 27719092
TI  - ?
AB  - Both nursing-led units and intermediate care have attracted much controversy over
      recent years. This paper provides a useful summary of the key sources and the
      current state of the debates, before going on to describe a questionnaire-based
      study.

PMID- 27719091
TI  - Website watch.
AB  - ? The Resuscitation Council is a leading UK membership organisation, whose
      website includes details on guidelines, medical information and reports relating
      to resuscitation, courses, important statements, publications and an A to Z index
      www.resus.org.uk/.

PMID- 27719093
TI  - Prioritising home care needs: research with older people from three ethnic
      minority community groups.
AB  - The National Service Framework for Older People has focused attention once again
      on the requirement to deliver services in ways which meet the needs of patients.
      In this study carried out in Manchester, and funded by the Joseph Rowntree
      Foundation, focus groups were used to explore views on home-care needs.

PMID- 27719094
TI  - Older people in the field of medication.
AB  - Focus group methodology is becoming ever more popular in healthcare research. In
      this Finnish study, five focus group discussions were conducted with a total of
      34 participants whose ages ranged from 65 to 85. Each group was facilitated by
      two researchers and the discussions were tape-recorded. Analysis of the data
      employed the concepts developed by Pierre Bourdieu.

PMID- 27719095
TI  - Describing an episode of home nursing care for elderly postsurgical cancer
      patients.
AB  - This American study focused on the home nursing care received by patients with
      cancers of the prostate, breast, gastrointestinal tract, head and neck, and lung.
      The ages of the 148 post-surgical patients in the sample ranged from 60 to 90
      years, with a mean age of 68.

PMID- 27719096
TI  - Know your complementary therapies Eileen Inge Herzberg Know your complementary
      therapies Age Concern Tel 0870 4422044 275pp L9.99 +L1.95 p&p 0 86242 309 0
      0862423090.
AB  - Overall, the content provides most enjoyable reading, with the emphasis very much
      on the practical approach to using complementary therapies. The book provides
      comprehensive coverage of familiar, well-known therapies as well as those which
      are less traditional and less well recognised, such as 'zero balancing'.

PMID- 27719097
TI  - ?
AB  - I recently left a senior academic post within the university to go 'back to my
      roots' and take up a full time post in a nursing home. While to some that may
      seem to be a strange career move, I'm sure that colleagues working within higher
      education will have an understanding of my motivation.

PMID- 27719098
TI  - The Care Homes Legal Handbook The Care Homes Legal Handbook Jeremy Cooper Jessica
      Kingsley Publishers 171pp L15.95 1 84310 0649 1843100649 [Formula: see text].
AB  - While this is a timely publication, its contents are already in part dated,
      demonstrating how quickly legislative changes occur. The information is presented
      in an accessible questions and answers format. Inevitably, while trying to
      acknowledge that all readers will not be lawyers, the language remains formal.

PMID- 27719100
TI  - Spirituality in Health Care Contexts Helen Orchard Spirituality in Health Care
      Contexts Jessica Kingsley Publishers 205pp L15.95 1 85302 969 6 1853029696.
AB  - What unites the contributors to this text is chaplaincy. In recent years the
      nature of hospital chaplaincy and concerns about how to meet the spiritual needs
      of patients has been of increasing concern to many practitioners. The
      significance of the interface between chaplains and nurses in meeting this need
      is addressed from several different perspectives.

PMID- 27719099
TI  - ?

PMID- 27719101
TI  - New publications.

PMID- 27719102
TI  - Death duties a responsibility too far?
AB  - In the areas of acute surgery and medicine, the changing role of the nurse, which
      is constantly developing and being extended in order to accommodate the reduction
      in junior doctors' hours, is well documented. But the new roles being forced upon
      nurses who work in nursing homes go unnoticed.

PMID- 27719104
TI  - Still Rockin!

PMID- 27719103
TI  - Promoting healthy skin in older people.
AB  - This article has proved to be a good source of educational material and practical
      guidance. As a mental health nurse who works with older adults over 65, I
      endeavour to practise holistic care. This article allowed for holistic care and I
      learnt about physical, biological, environmental and psychological issues
      surrounding the care of older people's skin.

PMID- 27719105
TI  - Practice development trials and triumphs.
AB  - There are strong reasons for developing practice in older people's health care
      but the concept is complex. Practice development means helping practitioners
      within their 'real world' context: helping them to find creative and positive
      ways forward through the demanding, often confusing and draining day-to-day
      trials and tribulations of practice. Practice development is a continuous journey
      without a defined end point or final destination. There are always improvements
      to be made, new ways of seeing things, discoveries to be made and challenges that
      need to be met ( Pritchard and Cooney 2002 ).

PMID- 27719106
TI  - The influence of cycling intensity upon cognitive response during inferred
      practice and competition conditions.
AB  - In many sport and exercise situations, cognitive performance is required under
      conditions of high physiological load and high cognitive anxiety. However, few
      studies have assessed all these components in situ. The current study sought to
      address this issue. Fourteen adults (9 males, 5 females) completed 2 incremental
      exercise trials (perceived competition or perceived practice) in a
      counterbalanced order. Cognitive performance, via a test of visual
      discrimination, rating of perceived exertion (RPE), heart rate (HR), blood
      lactate (Bla), and anxiety scores, was recorded at rest, 70% [Formula: see text]
      and 90% [Formula: see text]. Visual discrimination response times were faster at
      rest compared to 70% (P = 0.001) and 90% [Formula: see text] (P = 0.002) and at
      70% compared to 90% [Formula: see text] (P = 0.04) in the competitive condition.
      HR post-instructions (P = 0.0001), at 70% (P = 0.001) and 90% [Formula: see text]
      (P = 0.0001), was significantly higher in competition compared to practice. RPE
      was higher in the competitive condition compared to the practice condition (P =
      0.023). Cognitive anxiety intensity was significantly higher in the competitive
      condition, at 70% and 90% [Formula: see text] (P = 0.001). This study suggests
      that cognitive performance is more negatively affected when physiological arousal
      and cognitive anxiety are at their highest. Coaches and athletes should be
      mindful of such effects and seek to develop skills to offset such responses or to
      structure training to better represent competition.

PMID- 27719108
TI  - 'Basically, it's sorcery for your vagina': unpacking Western representations of
      vaginal steaming.
AB  - Vaginal steaming made global headlines in 2015 after its promotion by celebrity
      Gwyneth Paltrow. One of many female genital modification practices currently on
      offer in Anglo-Western nations - practices both heavily promoted and critiqued -
      vaginal steaming is claimed to offer benefits for fertility and overall
      reproductive, sexual or even general health and wellbeing. We analysed a
      selection of online accounts of vaginal steaming to determine the sociocultural
      assumptions and logics within such discourse, including ideas about women,
      women's bodies and women's engagement with such 'modificatory' practices. Ninety
      items were carefully selected from the main types of website discussing vaginal
      steaming: news/magazines; health/lifestyle; spa/service providers; and personal
      blogs. Data were analysed using thematic analysis, within a constructionist
      framework that saw us focus on the constructions and rationalities that underpin
      the explicit content of the texts. Within an overarching theme of 'the self
      improving woman' we identified four themes: (1) the naturally deteriorating,
      dirty female body; (2) contemporary life as harmful; (3) physical optimisation
      and the enhancement of health; and (4) vaginal steaming for life optimisation.
      Online accounts of vaginal steaming appear both to fit within historico
      contemporary constructions of women's bodies as deficient and disgusting, and
      contemporary neoliberal and healthist discourse around the constantly improving
      subject.

PMID- 27719109
TI  - Going the extra mile.
AB  - RCN RECORDS show that in the past seven years almost 370 nurses have registered
      doctoral theses: more than the total number of nurses who gained PhD status in
      the previous quarter of a century.

PMID- 27719107
TI  - Exposing athletes to playing form activity: outcomes of a randomised control
      trial among community netball teams using a game-centred approach.
AB  - This study evaluated whether exposing junior netball players to greater amounts
      of competition relevant activity (playing form activity) had an effect on game
      play outcomes and session involvement. A group-randomised controlled trial in one
      junior netball club in the Hunter Region, NSW, Australia. Ninety female athletes
      (mean age = 9.04 years, SD 1.53) were randomised by team (n = 11) into the
      intervention (n = 41) or 9-week wait-list control (n = 49) condition. The
      Professional Learning for Understanding Games Education into Sport (PLUNGE into
      Sport) programme was undertaken in the first half of nine training sessions (9 *
      30 min). The intervention exposed athletes to playing form activity through a
      coach development programme within training sessions. Athletes' decision-making,
      support and skill outcomes during a small-sided invasion game, and session
      involvement (pedometer step/min), were measured at baseline and 9-week follow-up.
      Linear mixed models revealed significant group-by-time intervention effects (P <
      0.05) for decision-making (d = 0.4) and support (d = 0.5) during game play, and
      in-session activity (d = 1.2). An intervention exposing athletes to greater
      levels of playing form activity, delivered via a coach education programme, was
      efficacious in improving athlete decision-making and support skills in game play
      and increasing athlete involvement during sessions.

PMID- 27719110
TI  - Nursing and midwifery research in scotland.
AB  - THE NURSING and midwifery workforce is the largest clinical staff group in
      NHSScotland, with 37,260 whole time equivalent qualified staff.

PMID- 27719112
TI  - Joined up thinking.
AB  - DURING A RECENT CONVERSATION, a director of nursing from the south east of
      England revealed to me that she knew little of her staff's research and
      development (R&D) achievements.

PMID- 27719111
TI  - A Northern Ireland perspective.
AB  - PRIORITIES FOR RESEARCH and development (R&D) in the health and personal social
      services (HPSS) in Northern Ireland are guided by the Research and Development
      Office, which was established in 1998, and through the R&D strategy, Research for
      Health and Well-being (R&D Office 1999).

PMID- 27719113
TI  - Skills for health.
AB  - Skills for Health, the UK sector skills council for health, has redesigned its
      website, writes Ruth Williams.

PMID- 27719114
TI  - Online education.
AB  - If you are interested in e-learning, the UK Healthcare Education Partnership
      between the RCN and three universities in England and Northern Ireland is
      offering online courses for healthcare professionals.

PMID- 27719115
TI  - Asylum seekers.
AB  - The health and social wellbeing of asylum seekers and refugees has become part of
      the remit of many healthcare professionals.

PMID- 27719116
TI  - Achieving potential through research and development: a Welsh perspective.
AB  - The guiding vision for the Welsh Assembly Government's strategic agenda, Wales: A
      better country ( WAG 2003 ), was for a fairer, more prosperous, healthier and
      better educated country.

PMID- 27719117
TI  - The Department of Health: championing investment and capacity building in nursing
      research.
AB  - THE DEPARTMENT OF HEALTH spends L650 million a year on research and development
      (R&D) and has a history of funding and supporting nursing research.

PMID- 27719118
TI  - Nurses' career progression slowed by new pay system.
AB  - Career progression in the nursing profession has significantly slowed as staff
      and organisations wait for the roll-out of the new NHS pay system, research
      suggests.

PMID- 27719119
TI  - Discharge decisions.
AB  - A new report on the experiences of older people after leaving hospital reveals
      that decisions that are made at the time of discharge can have long term
      consequences.

PMID- 27719120
TI  - Vantage point.
AB  - OF THE MYRIAD 'reality TV' programmes currently filling our screens, the only one
      that appeals to me is UKTV's Back to the Floor in which senior company managers
      return to their production or service areas to gain a sense of the dayto-day
      experiences of their staff.

PMID- 27719121
TI  - On the move.
AB  - Promotions / new appointments.

PMID- 27719123
TI  - Have your say.

PMID- 27719122
TI  - Conferences.
AB  - December 7-8 International Conference Centre, Birmingham.

PMID- 27719124
TI  - Moving the Agenda forward.
AB  - THREE YEARS AGO, Rafferty and colleagues celebrated the development of research
      and development (R&D) in the nursing professions by saying that 'there has rarely
      been a time in the history of nursing and midwifery research to be quite so
      optimistic about the future' ( Rafferty et al 2002 ).

PMID- 27719125
TI  - Liz bray.
AB  - What gets you out of bed in the morning? Professionally, I'm motivated by the
      autonomy I have at The Children's Trust, which means that what I do really makes
      a difference both to the working lives of nurses and to the quality of care we
      provide to children with multiple disabilities and complex health needs.

PMID- 27719126
TI  - Advice for older people.
AB  - A user friendly website designed to give older people advice on how to prevent
      themselves falling has been developed by the University of Southampton, Help the
      Aged, and healthcare software specialists Riomed.

PMID- 27719127
TI  - Social services in Wales.
AB  - Information on the quality of local authority social services in Wales is now
      available online.

PMID- 27719128
TI  - Mission impossible?
AB  - THERE ARE MOMENTS when experience tells you to be less earnest and direct, and a
      little more Delphic in style. At these times, half ideas can be useful and a
      little lack of clarity can be effective.

PMID- 27719129
TI  - Shared interests.
AB  - MANAGERS, IT HAS BEEN SAID, cannot read anything longer than two pages while
      academics cannot write anything less than 5,000 words ( Wistow 2001 ).

PMID- 27719130
TI  - Practical solutions.
AB  - RESEARCH BY NURSES, in common with other clinical research endeavours, offers
      opportunities to improve patient care by answering questions and providing
      evidence on which to base practices.

PMID- 27719132
TI  - ?
AB  - ONE OF the key functions of nursing leadership and nursing management is to
      assure the quality of patient experiences and the nursing contribution to patient
      outcomes.

PMID- 27719131
TI  - Untried primary care reforms 'risk lives' NMC elections.
AB  - Ministers could be risking patients' lives by implementing untried primary care
      reforms, according to the RCN.

PMID- 27719133
TI  - Network launched.
AB  - RCN Scotland last month launched its Lead Nurses in Community Health Partnerships
      (CHPs) Network. As well as acting as a forum for lead nurses to support each
      other and share best practice, the network will also explore how nurses can
      influence the developing CHP agenda.

PMID- 27719134
TI  - ?
AB  - Research focus: Itai Nyamatore (left), Barbara Featherstone (centre) and Denise
      Henry each received a research bursary worth L6,250 last month as winners of the
      RCN's Mary Seacole leadership development award. Ms Nyamatore, strategic nurse
      manager at Northampton Primary Care Trust will look at supporting named nurses
      and care co-ordinators; Ms Featherstone, a modern matron at Northamptonshire
      Healthcare NHS Trust, will try to improve mental health promotion among people
      from black and minority ethnic backgrounds with chronic physical conditions; and
      Ms Henry, a practice development midwife at Queen Charlotte's and Chelsea
      Hospital, London, will look at setting up and co-ordinating an integrated care
      pathway for women with female genital mutilation.

PMID- 27719135
TI  - Chart busters.
AB  - Poor design of bedside observational charts is causing staff to miss patient
      deterioration, a study has shown.

PMID- 27719195
TI  - Website watch.

PMID- 27719194
TI  - Still Rockin.

PMID- 27719197
TI  - Facing the future Facing the Future Oliver Valins Institute for Jewish Policy
      Research Tel 020 7935 8266 246pp L10 0 901113 29 8 0901113298.
AB  - This is not just a book for the Jewish community. Facing the Future is a
      worthwhile read for anybody who is concerned with the provision of long-term
      care. This is a well researched and sensitive book packed with statistical and
      sociological information about care homes in general. The section on choosing a
      home highlights the trauma of a situation that is all too easy for professionals
      to take for granted. Relatives interviewed spoke of the difficulty in knowing
      what to look for, how to 'judge kindness' and of the terrible sense of
      responsibility at having to choose a home for somebody else.

PMID- 27719198
TI  - The tranquil ark The Tranquil Ark Stuart Vassie The Book Guild Ltd Tel 01273
      472534 268pp L16.95hb 1 85776 620 2 1857766202.
AB  - This work of fiction is an absorbing read which portrays never-to-beforgotten
      characters in their daily life within a sheltered housing development. Vassie has
      convincingly spun a tale of unpleasant, paternalistic attitudes versus kindness
      to the residents as they react in different ways to the changes foisted upon
      them.

PMID- 27719199
TI  - Gentle exercises for the elderly (CD) Gentle exercises for the elderly (CD)
      Gallagher Rita Off stage productions compact disc L16.50.
AB  - Gentle Exercises for the Elderly is a CD which provides a programme of gentle
      exercises, for use particularly with older people and those who are confined to
      chairs. The instructor has a calming encouraging voice and the music is
      acceptable, creating a pleasant atmosphere. There should be some notes though, in
      the sleeve of the CD on the importance of exercise, plus the benefits.

PMID- 27719200
TI  - Events.
AB  - Our roundup of what's on.

PMID- 27719201
TI  - ?
AB  - I am currently reviewing the documentation we use for the care of the older
      person. The care pathways we use at present are very disease specific. I would be
      interested to find out if there are any areas that use care pathways that are
      specific to the older person.

PMID- 27719202
TI  - New publications.
AB  - Anne Squire Bailliere Tindall 376pp L17.99 ISBN 0 7020 2315 9 Aimed at nurses and
      other healthcare professionals who work with older people in community and
      residential environments.

PMID- 27719204
TI  - Milburn moves to halt care home crisis.
AB  - A package of measures to reform services for older people has been unveiled by
      health secretary Alan Milburn with the aim of increasing choice and halting the
      growing crisis in the care home sector.

PMID- 27719203
TI  - Screening and assessing the nutritional status of older people.
AB  - Nutritional status can be defined as 'the state of health produced by the balance
      between requirement and intake of nutrients' ( Barker 1996 ). When assessing or
      screening for malnutrition it is nutritional status that is considered.

PMID- 27719205
TI  - Back from the brink.
AB  - A package of measures to improve the care of older people and stabilise the care
      home sector has been announced by Alan Milburn. But the health secretary has
      warned that the extra resources must allow older people faster access to a wider
      range of services, rather than 'more of the same'.

PMID- 27719206
TI  - ?
AB  - After 50 years of Rockin', Bill Haley's original Comets arrive for their concert
      in Pakefield, Suffolk. Their hit single 'Rock around the clock' was recorded in
      1954 and their new CD collection contains the song 'We ain't dead yet'. Kicking
      off the concert Marshall Lytle, double bass player, announced 'We're very pleased
      to be here - we're very pleased to be anywhere!'

PMID- 27719207
TI  - Delayed discharge plan raises cash questions.
AB  - Latest government attempts to solve the enduring problem of delayed discharge
      have met with a cool response from nursing unions.

PMID- 27719208
TI  - A tool for the job.
AB  - In May 2002, the Department of Health published an audit tool to help social
      services departments (SSDs) improve services for older people from minority
      ethnic communities. Traditionally, health and social care providers in the UK
      have adopted a 'colour-blind' approach, seeking to provide universal services to
      everyone on the basis of their need, irrespective of who they are. More recently,
      we have come to understand that this can be discriminatory.

PMID- 27719209
TI  - Good neighbours: help or hindrance?
AB  - Our neighbour Enid is 92. She has lived alone in her house for over 50 years and
      is known to everyone in 'The Avenue'. Our neighbourhood has retained some of its
      former village environment and has a large older population who are very
      significant in our sense of community. Many have lived here since birth and pass
      on stories of when Queen Victoria visited. Our school is still housed in the
      original Victorian building and the children are taught about its heritage.

PMID- 27719210
TI  - Single assessment.
AB  - The single assessment process has been advocated as a cure-all for some of the
      duplication and inconsistency of approach to assessment experienced by many older
      people. Introduced as part of the National Service Framework for Older People (
      DoH 2000 ), the single assessment process(SAP) has generally been welcomed for
      its person centred approach and inclusion of older people. It is possible that
      with appropriate implementation older people will see less duplication and the
      avoidance of multiple professional assessments, which in turn could improve the
      care older people receive.

PMID- 27719211
TI  - Therapeutic touch in dementia care.
AB  - Touch, in its purest sense, is considered by many as a core aspect of care-giving
      and of the nurse-patient relationship. Touch is a fundamental element in nursing
      work and one of the most personally experienced of all communicative sensations.
      Some believe it to be the 'mother of the senses', symbolising caring and
      providing validation of existence as an individual ( Autton 1989 , Estabrooks and
      Morse 1992 , Weiss 1992).

PMID- 27719212
TI  - The quality of psychotropic drug prescribing in patients in psychiatric units for
      the elderly.
AB  - This retrospective study examined the quality of drug prescriptions in two units
      in Yorkshire. Separate results are given for prescriptions written for patients
      suffering from dementia and from functional psychiatric illness (such as
      depression, anxiety and psychosis).

PMID- 27719213
TI  - ?
AB  - At 32 years old, I have recently completed (April 2002) a diploma in mental
      healthnursing and have fulfilled my long-term goal/dream by working on a ward for
      older people. Sadly, I am slowly beginning to feel that my dream is slipping
      away, as I am looking towards seeking further employment, possibly in acute
      settings, due to the low morale and lack of support from up the hierarchy.

PMID- 27719214
TI  - ?
AB  - I am coming towards the end of a tough first year as a nursing student. Reading
      your recent article 'Improving student placements in nursing homes' (NOP July
      2002), I was disgusted that some students find six hours in a nursing home
      sufficient to learn about the job and about person-centred care. I have been in a
      mental health unit for ten weeks and am still learning about person-centred care.
      This cannot be achieved in a short time spent in a nursing home.

PMID- 27719215
TI  - Cash fix insufficient for people like Enid.
AB  - The additional L1 billion funding to go into social services by 2006 has been
      warmly welcomed, along with the key reforms announced recently by health
      secretary Alan Milburn ( pages 4 , 6 ). Increased funding is urgently needed to
      stabilise the care home market, and specifically to increase the fees that social
      services can offer. Even with the relaxation in the enforcement of environmental
      standards, the real costs of providing care home places have long exceeded social
      services fee rates, and L1 billion was exactly the uplift recommended in the
      recent Joseph Rowntree Foundation analysis of care home provision costs.

PMID- 27719216
TI  - Standing and moving.
AB  - I work as a ward manager on a 20-bed continuing care ward with some input into a
      respite care facility. My clinical area caters for older people who have
      neurological conditions, most commonly Alzheimer's disease, Lewy body disease and
      vascular dementia. I found this article to be of great benefit and I am certainly
      aware of the difficulties associated with maintaining the safe mobility of our
      patients. I intend to make greater use of my communication skills and especially
      non-verbal communication.

PMID- 27719217
TI  - Medical decisions for troubled breathing in nursing home residents.
AB  - This American paper reports on one section of a larger study of decision-making
      in nursing homes. The interface between the nursing home and local primary care
      services is often a problematic one. Respiratory problems are common in frail
      older people suffering from dementia, and pose difficult dilemmas for doctors,
      nurses and relatives.

PMID- 27719218
TI  - Drawing the line: the boundaries of volunteering in the community care of older
      people.
AB  - Volunteers play a vital role in the current 'mixed economy of care', but have not
      attracted a proportionate level of interest from researchers. In this English
      study, 14 volunteer schemes formed the purposive sample. Semi-structured
      interviews were carried out with the organisers of each scheme, but it proved
      difficult to interview volunteers themselves, as organisers were reluctant to
      release names and addresses.

PMID- 27719219
TI  - A feminist perspective on stroke rehabilitation: the relevance of de Beauvoir's
      theory.
AB  - The thoughts of Simone de Beauvoir have retained an important place in feminist
      scholarship. In this Norwegian paper, de Beauvoir's ideas on the different
      experiences of men and women are applied to the case of stroke rehabilitation.
      The authors argue that traditional approaches to rehabilitation, which often
      place it in the context of athletic activity, are less appropriate for women than
      for men. Indeed, they discuss one Norwegian study in which women patients stayed
      by their beds reading, while men roamed the corridors discussing their athletic
      and hunting exploits. The authors argue that such evidence should challenge
      healthcare professionals to devise rehabilitation regimes which take gender-based
      preferences into account. 48 references.

PMID- 27719325
TI  - List of Guest Reviewers.

PMID- 27719269
TI  - Examining coaches' perceptions of how their stress influences the coach-athlete
      relationship.
AB  - This study extends recent coach stress research by evaluating how coaches
      perceive their stress experiences to affect athletes, and the broader coach
      athlete relationship. A total of 12 coaches working across a range of team sports
      at the elite level took part in semi-structured interviews to investigate the 3
      study aims: how they perceive athletes to detect signals of coach stress; how
      they perceive their stress experiences to affect athletes; and, how effective
      they perceive themselves to be when experiencing stress. Following content
      analysis, data suggested that coaches perceived athletes able to detect when they
      were experiencing stress typically via communication, behavioural, and stylistic
      cues. Although coaches perceived their stress to have some positive effects on
      athletes, the overwhelming effects were negative and affected "performance and
      development", "psychological and emotional", and "behavioural and interaction"
      factors. Coaches also perceived themselves to be less effective when stressed,
      and this was reflected in their perceptions of competence, self-awareness, and
      coaching quality. An impactful finding is that coaches are aware of how a range
      of stress responses are expressed by themselves, and to how they affect athletes,
      and their coaching quality. Altogether, findings support the emerging view that
      coach stress affects their own, and athlete performance.

PMID- 27719329
TI  - ABCB1 polymorphisms and steroid treatment in children with idiopathic nephrotic
      syndrome.
AB  - BACKGROUND: The most common cause of nephrotic syndrome (NS) is idiopathic
      nephrotic syndrome (INS), also called nephrosis. Although most patients respond
      to steroid therapy, there is unequal response to treatment suggesting the
      involvement of genetic factors. The current study was conducted to evaluate the
      influence of two single nucleotide polymorphisms (SNPs) in ABCB1 (C3435T and
      C1236T) on the steroid treatment response in INS children. MATERIALS AND METHODS:
      Genotyping of ABCB1 C3435T and C1236T polymorphisms by real time PCR were
      conducted on 120 INS children, 80 steroid sensitive (SS) and 40 steroid resistant
      (SR). RESULTS: A significant difference in the distribution of ABCB1 C3435T and
      C1236T genotypes was observed between SS and SR patients. C1236T polymorphism was
      associated with steroid resistance in INS children (odds ratio: 2.27, 95 %
      confidence interval: 1.2-4.4; P = 0.012). The frequency of the T allele was
      significantly higher in SR than in SS patients (81.2 vs. 65.6%, respectively).
      The odds ratio for the C3435T polymorphism in response to steroid treatment was
      smaller than that of the polymorphism C1236T, and did not reach statistical
      significance (odds ratio: 1.1, 95 % confidence interval: 0.6-1.9; P = 0.77).
      CONCLUSION: Our results suggested that C1236T polymorphism in ABCB1 gene was
      associated with steroid resistance. A higher proportion of SR children had C1236T
      TT genotype and T allele, these patients may require other therapeutic
      strategies.

PMID- 27719379
TI  - A model to assess the cost-effectiveness of pharmacogenomics tests in chronic
      heart failure: the case of ivabradine.
AB  - Pharmacogenomics (PGx) tests have the potential of improving the effectiveness of
      expensive new drugs by predicting the likelihood, for a particular patient, to
      respond to a treatment. The objective of this study was to develop a
      pharmacoeconomic model to determine the characteristics and the cost
      effectiveness of a hypothetical PGx test, which would identify patients who are
      most likely to respond to an expensive treatment for chronic heart failure. For
      this purpose, we chose the example of ivabradine. Our results suggest that the
      use of a PGx test that could select a subgroup of patients to be treated with an
      expensive drug has the potential to provide more efficient drug utilization.

PMID- 27719380
TI  - Linking Traumatic Childhood Experiences to the Physical Health of Korean
      Adolescents in Out-of-Home Care through Depression and Anxiety.
AB  - The main purpose of this study is to assess whether the physical health of Korean
      adolescents in out-of-home care is affected directly by traumatic childhood
      experiences and/or indirectly through depression and anxiety. Study participants
      are 460 adolescents who are included in the first and second wave of the Panel
      Study on Korean Children in Out-of-Home Care. The data are analyzed using
      structural equation modeling. Our structural model finds no direct effects of
      traumatic experiences on physical health. Among the two types of trauma
      experiences, namely, family instability and violence experiences, only violence
      experiences affect physical health indirectly through depression and anxiety.
      Based on the results, practice implications for Korean adolescents in care are
      discussed.

PMID- 27719437
TI  - Is three the magic number? The role of ergonomic principles in cross country
      comprehension of road traffic signs.
AB  - Road sign comprehension plays an important part in road safety management,
      particularly for those drivers who are travelling in an unfamiliar country.
      Previous research has established that comprehension can be improved if signs are
      designed to adhere to ergonomic principles. However, it may be difficult for sign
      designers to incorporate all the principles into a single sign and may thus have
      to make a judgement as to the most effective ones. This study surveyed drivers in
      three countries to ascertain their understanding of a range of road signs, each
      of which conformed in varying degrees and combinations to the ergonomic
      principles. We found that using three of the principles was the most effective
      and that the most important one was that relating to standardisation; the colours
      and shapes used were key to comprehension. Other concepts which related to
      physical and spatial characteristics were less important, whilst conceptual
      compatibility did not aid comprehension at all. Practitioner Summary: This study
      explores how road sign comprehension can be improved using ergonomic principles,
      with particular reference to cross-border drivers. It was found that
      comprehension can be improved significantly if standardisation is adhered to and
      if at least three principles are used.

PMID- 27719441
TI  - Personal Identity and the Schizophrenic Process.

PMID- 27719438
TI  - The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience,
      and Creative Problem Solving.
AB  - Developing methods for improving creativity is of broad interest. Classic
      psychedelics may enhance creativity; however, the underlying mechanisms of action
      are unknown. This study was designed to assess whether a relationship exists
      between naturalistic classic psychedelic use and heightened creative problem
      solving ability and if so, whether this is mediated by lifetime mystical
      experience. Participants (N = 68) completed a survey battery assessing lifetime
      mystical experience and circumstances surrounding the most memorable experience.
      They were then administered a functional fixedness task in which faster
      completion times indicate greater creative problem-solving ability. Participants
      reporting classic psychedelic use concurrent with mystical experience (n = 11)
      exhibited significantly faster times on the functional fixedness task (Cohen's d
      = -.87; large effect) and significantly greater lifetime mystical experience
      (Cohen's d = .93; large effect) than participants not reporting classic
      psychedelic use concurrent with mystical experience. However, lifetime mystical
      experience was unrelated to completion times on the functional fixedness task
      (standardized beta = -.06), and was therefore not a significant mediator. Classic
      psychedelic use may increase creativity independent of its effects on mystical
      experience. Maximizing the likelihood of mystical experience may need not be a
      goal of psychedelic interventions designed to boost creativity.

PMID- 27719446
TI  - Pharmacological treatment of fibromyalgia: is the glass half empty or half full?

PMID- 27719508
TI  - Public Knowledge of HIV/AIDS in Three Rural Communities of Nigeria.
AB  - This study aimed at assessing knowledge of HIV/AIDS among residents of three
      rural communities in Nigeria. A total of 371 persons residing in selected rural
      communities were recruited for this study. A structured questionnaire was used to
      collect data from all participants. Results of the study showed a generally high
      level of awareness of HIV/AIDS in all communities surveyed. However, among study
      participants, knowledge of mode of prevention and management of HIV infection was
      poor as was knowledge of HIV status and readiness to utilize free voluntary
      counseling and testing for HIV/AIDS services. Scale-up of HIV/AIDS education by
      relevant health authorities is strongly advocated.

PMID- 27719511
TI  - Change of Editors.

PMID- 27719512
TI  - Brief Communications.

PMID- 27719509
TI  - Essential and toxic elements in commercial baby food on the Spanish and Serbian
      market.
AB  - About 10 heavy elements were determined in 90 samples of baby food collected from
      Spanish and Serbian market. The results indicated that iron, manganese and copper
      were most frequently detected. Tin was the predominant toxic element in both
      Spanish and Serbian samples, with occurrence frequencies of 12.5% and 10.0%,
      respectively. Element intake for Spanish and Serbian infants were estimated and
      compared with the recommended reference values, for the majority of elements
      being lower than one. However, iron and manganese intake through consumption of
      infant/follow-on formulas were assessed to be higher than the respective daily
      intakes. Particular attention should be paid to the exposure of infants who
      consume porridges made of vegetables and fish or chicken, because they may ingest
      certain elements, particularly arsenic and lead, at levels that exceed the
      reference toxicological values. Principal component analysis (PCA) was applied to
      classify and distinguish the different types of baby food.

PMID- 27719515
TI  - Women, Career Changes, and the New Self.

PMID- 27719516
TI  - The Psychodynamic Life Narrative.

PMID- 27719517
TI  - Ego Boundary as Process.

PMID- 27719514
TI  - Lifetime alcohol use and cognitive performance in older adults.
AB  - Substance use is an important clinical issue in the older adult population. As
      older adults are susceptible to cognitive disorders, the intersection of the
      fields of substance use and cognitive neuroscience is an active area of research.
      Prior studies of alcohol use and cognitive performance are mixed, and
      inconsistencies may be due to under- or over-adjustment for confounders. This
      article adds to this literature by conducting a secondary analysis of self
      reported lifetime history of alcohol use and cognitive performance in older
      adults (n = 133). It was hypothesized that current alcohol users would have
      poorer cognitive performance compared to never/minimal and former alcohol users.
      Older adult participants were classified into never/minimal alcohol users, former
      alcohol users, and current alcohol users. A neurocognitive battery included a
      global cognitive measure and individual measures of attention, memory, fluency,
      and executive function. A directed acyclic graph-based approach was used to
      select variables to be included in the multiple linear regression models. Though
      unadjusted analyses showed some significant associations between alcohol use and
      cognitive performance, all associations between alcohol use and cognitive
      performance were eliminated after adjusting for age, education, sex, race, and
      smoking pack years. Alcohol drink years were not significantly associated with
      cognitive performance among current and former alcohol users. These results
      suggest that lifetime alcohol use is not significantly associated with cognitive
      performance in older adults after adjustment for key confounders. Inconsistencies
      in prior studies may be due to uncontrolled confounding and/or unnecessary
      adjustment of mediators and/or colliders.

PMID- 27719518
TI  - Men in Extreme Conditions.

PMID- 27719519
TI  - Pathology as "Personal Growth".

PMID- 27719520
TI  - Big Me and Little Me.

PMID- 27719522
TI  - Feuchtersleben and Szasz: A Rejoinder.

PMID- 27719521
TI  - Alfred Hodgin Stanton, M.D. 1912-1983.

PMID- 27719523
TI  - Szasz, Feuchtersleben and the Philosophy of Psychiatry: Reply to Szasz.

PMID- 27719526
TI  - Design of a 3-dimensional visual illusion speed reduction marking scheme.
AB  - To determine which graphic and color combination for a 3-dimensional visual
      illusion speed reduction marking scheme presents the best visual stimulus, five
      parameters were designed. According to the Balanced Incomplete Blocks-Law of
      Comparative Judgment, three schemes, which produce strong stereoscopic
      impressions, were screened from the 25 initial design schemes of different
      combinations of graphics and colors. Three-dimensional experimental simulation
      scenes of the three screened schemes were created to evaluate four different
      effects according to a semantic analysis. The following conclusions were drawn:
      schemes with a red color are more effective than those without; the combination
      of red, yellow and blue produces the best visual stimulus; a larger area from the
      top surface and the front surface should be colored red; and a triangular prism
      should be painted as the graphic of the marking according to the stereoscopic
      impression and the coordination of graphics with the road.

PMID- 27719530
TI  - A sideways look at images of age.

PMID- 27719529
TI  - Meeting the holistic needs of dependent older people.

PMID- 27719532
TI  - Mental capacity assessments and discharge decisions.
AB  - Professionals may have agendas that conflict with the person under their care as
      their dominant consideration is often safety. This may arise from a genuine
      concern about welfare, but may also involve fear of litigation from an adverse
      incident following discharge.

PMID- 27719533
TI  - ?
AB  - In older people with hip fracture, chest infection and heart failure are the most
      common postoperative complications and lead to increased mortality. In patients
      who developed postoperative heart failure, mortality in this study was 65 per
      cent at 30 days and 92 per cent were dead by one year. Mortality for those who
      developed a chest infection was 45 per cent at 30 days.

PMID- 27719534
TI  - Depression.

PMID- 27719536
TI  - ?
AB  - Age Concern has launched two new factsheets for older same-sex couples on
      benefits and civil partnerships. The first gives a brief outline of the changes
      to pensions and benefits for same-sex partners following the introduction of the
      Civil Partnership Act in December, while the second provides information for
      couples considering registering a partnership under the act. The factsheets,
      which are available from the Age Concern website ( www.ace.org.uk ), were
      launched ahead of LGBT History Month, which runs during February and celebrates
      the histories of lesbian, gay, bisexual and transgender people in the UK. For
      more information, see www.lgbthistorymonth.org.uk.

PMID- 27719535
TI  - Department of health England.
AB  - You do know about the older people area of the Department of Health (DH) website,
      don't you? The reason for asking is that it has a slight dusty feel, as if no one
      visits very often. It is easy enough to find: just go to the A-Z list of topics
      on the homepage of the main site and look under 'O'. On the 'Older people's
      services' page you will be see a message that says the section is intended as a
      resource for NHS organisations and local authorities, but that older people may
      find it useful too. Well, they may. On the other hand, unless they need 'a
      prospectus for grant applications' for a Partnership for Older People project,
      they may not.

PMID- 27719537
TI  - Care services helping more older people to live alone.
AB  - The number of older people who require a high level of support but who are living
      independently is rising, according to government figures.

PMID- 27719538
TI  - Men more vulnerable to loneliness in older age, say campaigners.
AB  - Older men lack social links and contacts, making them vulnerable to isolation and
      loneliness, a leading charity has said.

PMID- 27719539
TI  - QOF is a 'missed opportunity' to improve osteoporosis care.
AB  - Campaigners have said that the decision not to include osteoporosis in the list
      of conditions covered by the General Medical Services (GMS) contract is a missed
      opportunity.

PMID- 27719540
TI  - Patients with prostate cancer have 'unacceptable' experience of NHS.
AB  - Far too many men with prostate cancer are not receiving appropriate care and
      support from the NHS and are given poor quality and inconsistent information, the
      Prostate Cancer Charity has said.

PMID- 27719543
TI  - Stop elder abuse campaign.
AB  - A national campaign aimed at stopping elder abuse has been launched by Help the
      Aged in partnership with Action on Elder Abuse.

PMID- 27719541
TI  - Leaders need followers to sustain change.
AB  - I feel inspired. I've been celebrating the culmination of the programme to
      develop the leadership capabilities of nurses working with older people funded by
      the Department of Health (England) and run by the Royal College of Nursing. The
      third such DH-funded programme, this comprised 23 facilitated days, action
      learning, mentorship, shadowing and patient-centred, work-based learning. Eighty
      nurses from the NHS, the independent sector, social care and a range of other
      services completed the course.

PMID- 27719544
TI  - Empowering the people.
AB  - Q: What does your job entail? A: In general my job involves working with health
      and social care professionals, the voluntary sector and with older people
      themselves to improve the health care of older people. The role is broad in scope
      and varies according to national and local priorities, but includes the
      following: service and practice development; expert practice; research, education
      and training; and professional leadership for nurses and nursing.

PMID- 27719545
TI  - Caring for Carers: Recognising, Valuing and Supporting the Caring Role.
AB  - The Department of Heath, Social Services and Personal Safety (DHSSPS) has
      published a new strategy aimed at providing support for thousands of carers
      across Northern Ireland.

PMID- 27719548
TI  - Brief Communication.

PMID- 27719551
TI  - Who Seeks Job Resources, and Who Avoids Job Demands? The Link Between Dark
      Personality Traits and Job Crafting.
AB  - Although job crafting has been linked repeatedly to positive employee and
      organizational outcomes, its detrimental side has not been well explored. To
      understand the way dark personality traits affect the type of crafting in which
      employees engage, this research focuses on two frameworks: the PEN (psychopathy,
      extraversion, and neuroticism) framework and the Dark Triad (narcissism,
      psychopathy, and Machiavellianism). In Study 1, we collected data on the PEN
      traits and job crafting from 155 individuals in various occupations. We found
      that neuroticism was negatively related to seeking structural job resources,
      whereas psychoticism was negatively related to seeking social job resources. We
      also found that extraversion was positively related to seeking structural and
      social job resources and to seeking challenging job demands. In Study 2, we
      examined how the Dark Triad traits predicted job crafting among police officers
      (N = 135). The results showed that narcissism was positively related to seeking
      social job resources and challenges, whereas psychopathy was negatively related
      to seeking social resources. Age and narcissism were positive predictors of
      reducing job demands. We conclude that personality plays an important role when
      choosing how to craft one's job. We discuss the practical implications of these
      findings.

PMID- 27719550
TI  - Development of shell cross-linked nanoparticles based on boronic acid-related
      reactions for self-regulated insulin delivery.
AB  - Shell cross-linked nanoparticles were fabricated by the complexation of poly(3
      methacrylamido phenylboronic acid) (PMAPBA) and thiolated chitosan (chitosan-SH)
      via boronic acid-related reactions. The formation of PMAPBA/chitosan-SH
      nanoparticles was confirmed by transmission electron microscopy, dynamic light
      scattering, and UV spectroscopy. The nanoparticles had a narrow size distribution
      with a relatively high positive charge density, and the size and zeta potential
      of the nanoparticles correlated with the chitosan-SH concentration. Furthermore,
      owing to the cross-linking of the nanoparticle shell, insulin was encapsulated in
      the nanoparticles with a loading capacity of up to 18%. The release of insulin
      from the nanoparticles slowed down because of the presence of disulfide bonds and
      increased with increasing glucose level in the medium. The structure of the
      released insulin was not distorted. More importantly, the nanoparticles had good
      cytocompatibility, as demonstrated by in vitro experiments. The simplicity of
      this strategy along with a high loading capacity, glucose sensitivity, and
      cytocompatibility of the produced nanoparticles should significantly boost their
      application in self-regulated insulin delivery.

PMID- 27719552
TI  - Response to Stillman and Walker.

PMID- 27719554
TI  - Viewpoint.

PMID- 27719559
TI  - Contributions by the Society for Life History Research on Psychopathology.

PMID- 27719562
TI  - Viewpoint.

PMID- 27719560
TI  - List of Guest Reviewers.

PMID- 27719563
TI  - Parental Mental Disorder and Offspring Criminal Behavior.

PMID- 27719565
TI  - Comment on Schwartz.

PMID- 27719564
TI  - Viewpoint.

PMID- 27719566
TI  - Comment on Schwartz.

PMID- 27719567
TI  - Responses to Shapiro and Silber.

PMID- 27719569
TI  - Single Case and Small Sample Reports.

PMID- 27719622
TI  - Phthalates in plastic bottled non-alcoholic beverages from China and estimated
      dietary exposure in adults.
AB  - Concentrations of six phthalates were determined in 69 plastic bottled non
      alcoholic beverages collected from marketplaces in China. Di-n-butyl phthalate
      (DBP) and di-(2-ethylhexyl)-phthalate (DEHP) were the most detected compounds
      with frequencies of 100%. Dimethyl phthalate was found less, with a mean
      frequency of almost 34%. The samples were divided into seven groups. The
      frequencies of phthalates in these groups ranged from 6.67% to 100%, which
      indicated that different types of beverages were differently contaminated by
      phthalates. DEHP contained the highest mean and median concentrations (1.60 ng g
      1 and 0.62 ng g-1), followed by DBP (1.34 ng g-1 and 0.27 ng g-1). For DBP, the
      highest phthalate concentration of 14.3 ng g-1 was measured. The results of
      estimated daily intake (EDI) showed that the risk of Chinese adults exposed to
      these 6 phthalates in beverages examined was lower than the reference doses as
      suggested by the United States Environmental Protection Agency. The range of EDI
      values was between 1.77 * 10-4 MUg kg-bw-1 day-1 and 0.478 MUg kg-bw-1 day-1.

PMID- 27719623
TI  - Caffeine Catalyzed Synthesis of Tetrahydrobenzo[b]pyran Derivatives: Synthesis
      and Insight into Kinetics and Mechanism.
AB  - AIM AND OBJECTIVE: Tetrahydrobenzo[b]pyran derivatives are considered as a
      special class in drug research because of their various biological and
      pharmacological benefiting usages. In the current work, we developed new
      synthetic methods for the preperation of tetrahydrobenzo[b]pyran derivatives
      using arylaldehydes 1, malononitrile 2 and dimedonein 3 in the presence of
      caffeine as catalyst as a cheap, easily accessible, biodegradable and green
      catalyst. Moreover, for the first time, we have described kinetic results
      together along with detailed mechanistic studies of the synthetic reaction of a
      derivative of 4Htetrahydrobenzo[ b]pyran based on a global kinetic analysis
      methodology using UVvis spectrophotometry apparatus. MATERIAL AND METHOD:
      Products were characterized by comparison of physical data with authentic samples
      and spectroscopic data (IR and NMR). Infrared (IR) spectra were recorded on a
      JASCO FT IR 460 plus spectrometer. 1H nuclear magnetic resonance (NMR) spectra
      were obtained with a Bruker DRX 400 Advance spectrometer and using deuterated
      dimethylsulfoxide (DMSO) and acetone as solvents. Thin layer chromatography (TLC)
      was performed on Silica-gel polygram SILG/UV 254 plates. Rate constants are
      presented as an average of several kinetic runs (at least 6-10) and are
      reproducible within +/- 3%. The overall rate of reaction is followed by
      monitoring the absorbance changes of the products versus time on a Varian (Model
      Cary Bio-300) UV-vis spectrophotometer with a 10 mm light-path cell. RESULTS: For
      optimization, the reaction of benzaldehyde (1 mmol), malonitrile (1 mmol) and
      dimedone (1 mmol) was investigated. The desired results were obtained at 70 
      degrees C in the presence of (20 mol %) caffeine in H2O: EtOH (2:1). Moreover,
      the overall order of reaction for the formation of a 4Htetrahydrobenzo[ b]pyran
      derivative in the presence of caffeine followed second-order kinetics and the
      partial orders with regard to 4-nitrobenzaldehyde 1, malononitrile 2 and dimedone
      3 were one, one and zero, respectively. CONCLUSION: It was observed that the
      yield was a function of temperature, as the yield increased, the reaction
      temperature rose. At 70 oC, the product was obtained with an excellent yield and
      higher temperatures did not increase the reaction yield any more. Also, 20 mol%
      was elected as a suitable amount of catalyst for this reaction. It is understood
      from the result that the rate of reaction speeds up in a solvent with a high
      dielectric constant (H2O/EtOH, 2:1) compared to those with a low dielectric
      constant (Ethanol and methanol) at all temperatures. In the studied temperature
      range, the second-order rate constant of the reaction was inversely proportional
      to the temperature, which was in agreement with the Arrhenius and Eyring
      equations. It was obvious that the high positive values of the activation
      parameters leads to a stiff reaction progress. The first step of the proposed
      mechanism was identified as a rate-determining step (k1) and this was confirmed
      based on the steady-state approximation.

PMID- 27719624
TI  - Treatment Possibilities for Psychosis in Parkinson's Disease with An Emphasis on
      the Newly Approved Drug: Pimavanserin.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder with
      prominent motor and non-motor symptoms. Psychosis develops in over 40% of PD
      patients and it is one of the most distressing symptoms for patients and
      caregivers alike. Until recently, atypical antipsychotics, clozapine and
      quetiapine were used to treat psychotic symptoms, but treatment was associated
      with substantial concerns for side-effects of clozapine and unfounded efficacy
      for quetiapine. Extensive research has shown that the antipsychotic effect of
      these drugs could be attributed to serotonin 2a receptor (5-HT2A) triggered
      mechanisms. A selective 5-HT2A inverse agonist, pimavanserin, has been developed,
      investigated and has gained approval in April 2016 in the US for the treatment of
      hallucinations and delusions in PD. In this review we primarily focus on
      psychosis in PD, the current treatment possibilities and the new, emerging
      therapy, pimavanserin, a selective 5-HT2A inverse agonist. All articles were
      reviewed in this topic and indexed in PubMed with keywords: Parkinson's disease
      psychosis, serotonin 2a receptor inverse agonist, clozapine, quetiapine,
      pimavanserin.

PMID- 27719625
TI  - Updates on Therapeutics in Clinical Trials for Spinal Cord Injuries: Key
      Translational Applications of Human Embryonic Stem Cells-Derived Neural
      Progenitors.
AB  - Injuries to the spinal cord often have devastating physiological impacts due to
      the organ's vital role in neuro-impulse communications between muscles and the
      brain. Spinal Cord Injuries (SCIs) have recently been estimated to affect up to
      80,000 individuals per year worldwide, with most occurring following a traumatic
      event. Unfortunately, effective treatments standardised globally for patients
      with SCIs have not yet been established. For many years, inadequate understanding
      of the complexities of the Central and Peripheral Nervous Systems and
      Neurogenesis has limited progression towards effective cures. However, in the
      last century, scientific advancements have generated new paradigms for medical
      treatments of SCIs. Basic as well as translational studies have progressed to
      such an extent that many kinds of protective and regenerative therapeutics are
      available in clinical trials. In particular, uncovering the mechanisms
      responsible for controlling the pluripotent state of Human Embryonic Stem Cells
      (hESCs) was proved vital for recognizing the prospective role in regenerative
      medicine for SCIs. Elucidating knowledge of neurogenesis alongside hESCs in
      relation to SCIs has been crucial for critical assessments of the existing
      translational therapeutic strategies for SCIs.

PMID- 27719626
TI  - Metabolic Inhibitors as Antiparasitic Drugs: Pharmacological, Biochemical and
      Molecular Perspectives.
AB  - BACKGROUND: Human diseases caused by the infectious parasites have been one of
      the major problems throughout the evolutionary journey. Protozoan and metazoan
      parasitic infections result in a large number of deaths, disabilities and socio
      economic loss worldwide to date. Despite the best efforts for developing suitable
      antiparasitics, these infections take a massive toll on human health. The
      prevalence of emerging resistance to the existing drugs, lack of efficacy and
      toxic side effects are as added complications. Being enlisted under 'neglected'
      category, serious diseases like leishmaniasis, filariasis, trypanosomiasis etc.
      have failed to draw attention of the governments as well as the pharmaceutical
      companies. Thus, target specific as well as cost-convenient therapy needs to be
      employed for the treatment of these diseases and selective targeting of metabolic
      pathways appears to be the most promising mean. METHODS: In this context, quality
      works have been explored for screening either anti-metabolic drugs or selective
      targets in different groups of parasites. Moreover, complete genome sequencing
      and metabolomic profiling have provided the initiatives to search for new lethal
      targets in parasites. RESULTS: New metabolic targets are being reported from
      different organelles and other sub-cellular compartments of parasites such as
      mitochondrion, kinetoplast, apicoplast, glycosome, hydrogenosome, acidocalcisome,
      plasma membrane, cytoskeleton, etc. Herein, unique findings achieved in
      identifying new antimetabolic drugs or targets and studying their molecular mode
      of actions have been reviewed by incorporating existing and upcoming approaches.
      CONCLUSION: Considering the alarming scenario of diseases caused by parasites
      globally, this paper provides a comprehensive review to the scientific community
      on the development of novel interventions based on metabolic targets to combat
      the challenges posed by parasites.

PMID- 27719627
TI  - Role of Reactive Oxygen Species in Premature Ageing of the Female Reproductive
      Function.
AB  - Industrial xenobitics, as well as endogenous damaging factors, such as L
      homocysteine, are a well-known source of reactive oxygen species that disrupt
      biological processes. Among many others, luteinizing hormone releasing hormone
      synthesis and secretion mediated by a variety of neurotransmitters, which are
      under control of the hypothalamus and pineal gland, may be put in peril by
      reactive oxygen species. Their formation can be one of the reasons for the
      reproductive function shutdown in ageing as the generic response to the damaging
      factors independent of their nature. We review recent findings demonstrating the
      role of reactive oxygen species in disrupting the circadian signal originated in
      the main pacemaker of the organism, the suprachiasmatic nuclei of the
      hypothalamus, on its way to the hypothalamic areas responsible for the
      luteinizing hormone preovulatory surge.

PMID- 27719628
TI  - Consciousness, Functional Networks and Delirium Screening.
AB  - BACKGROUND: Consciousness, the medium of sentient thought, requires integrity of
      functional networks and their connectivity. In health, they function as a co
      operative but mutually exclusive paradigm of introspection versus external
      awareness subserved via the Default Mode Network and Task Positive State,
      respectively. Higher thinking in the conscious state is then segregated according
      to need. There is research evidence to suggest that functional networks may be
      impacted in disorders of consciousness and conceptual support for a mechanistic
      role in delirium. This potentially central aspect of delirium manifestation is
      relatively unexplored. OBJECTIVE: This article describes the role of disrupted
      functional networks in delirium. How this relates to current understanding of
      delirium neurobiology and the ramifications for clinical diagnosis is discussed.
      METHOD: A review of the role of functional networks, particularly DMN and TPN,
      has been undertaken with respect to health and delirium. An exploration of how
      symptoms of delirium may be related to functional network aberrancy has been
      undertaken. Implications for research and clinical practice in delirium have been
      presented. RESULTS: In delirium, a disturbance of consciousness, the DMN is
      pathologically co-activated and functional cortical connectivity is compromised.
      The clinical correlate is of an experiential singularity where internal and
      external drivers become indistinguishable, reality and delusion merge and the
      notion of self is effaced. Our group propose that functional network disruption
      in conjunction with cortical disconnectivity is central to the mechanism of
      delirium. Clinical tools may exploit the neurobiology of delirium to improve its
      diagnosis and an example of such a simple screening instrument (SQeeC) is
      provided. CONCLUSION: Functional networks are critically disrupted in delirium
      and may be central to clinical features. A better understanding of the
      neurobiology of delirium will generate research opportunities with potential for
      therapeutic gains in detection, diagnosis, and management.

PMID- 27719630
TI  - Death by Insulin: Management of Self-Harm and Suicide in Diabetes Management.
AB  - Suicide is the tenth leading cause of death in Americans of all ages. Presence of
      a chronic medical illness (e.g. Diabetes mellitus) increases the risk of suicide.
      The goal of this review is to examine the relationship between diabetes and
      depression, as well as diabetes and suicide. Earlier this year, the U.S.
      Preventive Task Force (USPTF) escalated their recommendation for depression to
      include not only routine screening for depression but additional focus on active
      follow up that requires measurement based care. As a result, it is important that
      persons with diabetes are also screened for suicidal ideation in the presence of
      a mood disorder. Due to the higher risk and access to potentially lethal
      medications in persons with diabetes, risk mitigation procedures should be in
      place that includes not only depression and suicide screening but also the use of
      inter-disciplinary teams. Appropriate medical monitoring is essential following a
      suicide attempt to avoid death particularly because these patients are prone to
      repeat attempts.

PMID- 27719629
TI  - Human Umbilical Cord Stem Cell Xenografts Improve Cognitive Decline and Reduce
      the Amyloid Burden in a Mouse Model of Alzheimer's Disease.
AB  - INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia. The
      search for new treatments is made more urgent given its increasing prevalence
      resulting from the aging of the global population. Over the past 20 years, stem
      cell technologies have become an increasingly attractive option to both study and
      potentially treat neurodegenerative diseases. Several investigators reported a
      beneficial effect of different types of stem or progenitor cells on the pathology
      and cognitive function in AD models. Mouse models are one of the most important
      research tools for finding new treatment for AD. We aimed to explore the possible
      therapeutic potential of human umbilical cord mesenchymal stem cell xenografts in
      a transgenic (Tg) mouse model of AD. METHODS: APP/PS1 Tg AD model mice received
      human umbilical cord stem cells, directly injected into the carotid artery. To
      test the efficacy of the umbilical cord stem cells in this AD model, behavioral
      tasks (sensorimotor and cognitive tests) and immunohistochemical quantitation of
      the pathology was performed. RESULTS: Treatment of the APP/PS1 AD model mice,
      with human umbilical cord stem cells, produced a reduction of the amyloid beta
      burden in the cortex and the hippocampus which correlated with a reduction of the
      cognitive loss. CONCLUSION: Human umbilical cord mesenchymal stem cells appear to
      reduce AD pathology in a transgenic mouse model as documented by a reduction of
      the amyloid plaque burden compared to controls. This amelioration of pathology
      correlates with improvements on cognitive and sensorimotor tasks.

PMID- 27719631
TI  - Understanding the Action of Indolizines as Biologically Active Moieties: A
      Molecular Dynamics Study.
AB  - BACKGROUND: Indolizines represent a class of heteroaromatic compounds, of
      pharmacological importance, containing two condensed 5- and 6-memebered rings
      bridged by a nitrogen atom. Despite indolizine is an important medicinal moiety,
      a detailed view on the mechanism of action of biologically active indolizines is
      unavailable. OBJECTIVE: The study of ligand-enzyme affinity is of high interest;
      description of characteristics (energetic and geometric ones) of ligand binding
      to the active sites of an enzyme could be useful in understanding the action
      mechanism of a given ligand on the concerned enzyme. METHOD: After conducting a
      QSAR study, to predict IC50 (on 15-LO protein from soybeans) of indolizine
      derivatives and a docking study of indolizines on Beta lactamase and Nicotinamide
      phosphoribosyltransferase proteins [1], a molecular dynamics analysis was
      performed on one of the indolizine derivatives, complexed to the above proteins.
      RESULTS: The performed molecular dynamics study led to the identification of
      interactions responsible for the stabilization of complexes of the chosen ligand
      (i.e., indolizine derivative) with the considered enzymes and the specificity of
      the ligand interaction as well. The structural data and enthalpy values clearly
      indicate the differences in the behavior of ligand at the active sites of the
      three investigated enzymes. Among the studied proteins, the hydrophobicity of the
      active site of Nicotinamide phosphoribosyltransferase seems to be the main factor
      in promoting the interaction enzyme-ligand, much more manifested in this case, in
      comparison to the other two proteins Beta lactamase and Nicotinamide
      phosphoribosyltransferase. CONCLUSION: The present paper discusses a possible
      mechanism of interaction of an indolizine derivative with three enzyme proteins,
      providing information for future work in this topic.

PMID- 27719632
TI  - Miconazole Nitrate-loaded Microparticles For Buccal Use: Immediate Drug Release
      and Antifungal Effect.
AB  - BACKGROUND: Miconazole nitrate has been widely employed in treatment of oral
      mycoses, however your immediate bio-availability and location in the affected
      area is critical. OBJECTIVE: The aim of this study was to prepare and evaluate
      Eudragit(r) L100 and Gantrez MS-955 microparticles containing miconazole nitrate
      for oral delivery. METHODS: Microparticles were prepared by spray-drying method
      to achieve high encapsulation efficiency and increase the drug solubility. The
      microparticles were formed containing 10% and 20% of drug on polymer Eudragit(r)
      L100 (E10 and E20), Gantrez MS-955 (G10 and G20) or their combination (EG10 and
      EG20). The influence of formulation factors (polymer:drug ratio, type of polymer)
      on yield percent, encapsulation efficiency, particle size, Fourier-transformed
      infrared spectroscopy (FTIR), X-ray diffraction, differential scanning
      calorimetry, in vitro drug release and antifungal activity were investigated.
      RESULTS: Acceptable yield, micrometer-sized and drug-loading efficiencies higher
      than 89% were obtained. No change in FTIR assignments was recorded after the
      microencapsulation procedure. X-ray and differential scanning calorimetry studies
      revealed amorphous/non-crystalline formulations. Miconazole nitrate
      microparticles provided a remarkable increase of dissolution rate of the drug.
      Miconazole nitrate and G10, G20 and EG20 microparticles fitted to biexponential
      kinetic model, and E10, E20 and EG10 microparticles, monoexponential kinetic
      model. The antifungal activity test demonstrated that miconazole nitrate
      microparticles possessed the same anti-Candida albicans activity as the pure
      drug. CONCLUSION: These results indicate that miconazole nitrate-microparticles
      are feasible carriers for increased release of miconazole at oral environment.

PMID- 27719633
TI  - The Efficiency of Tat Cell Penetrating Peptide for Intracellular Uptake of HIV-1
      Nef Expressed in E. coli and Mammalian Cell.
AB  - BACKGROUND: Cell penetrating peptides (CPPs) or protein transduction domains
      (PTDs) have been known as a new field in cargo delivery. These peptides such as
      Tat, Pep-1 and Cady-2 are able to deliver genes and biologically active proteins
      to cytoplasmic compartments via the plasma membrane. METHODS: In current study,
      the efficiency of pEGFP-N1 eukaryotic vector for expression of HIV-1 Tat- Nef
      fusion was evaluated in HEK-293T cells using TurboFect transfection reagent. In
      addition, the recombinant GST-Tat-Nef protein was generated in E. coli and
      transfected using two amphipathic CPPs (Pep-1 and Cady-2) into mammalian cells.
      The size and morphology of the CPP/GST-Tat-Nef complexes were evaluated by
      scanning electron microscopy (SEM), Zetasizer, and SDS-PAGE. The transfection of
      HIV-1 GST-Tat-Nef protein was also analyzed using SDS-PAGE and western blotting.
      RESULTS: Our data indicated that the recombinant GST-Tat-Nef protein generated in
      BL21 strain migrated as a clear band of ~ 52 kDa in SDS-PAGE. The results of SEM
      and Zetasizer confirmed the formation of protein/ Pep-1 or protein/ Cady-2
      nanoparticles less than 200 nm in diameter. Tat CPP fused to Nef protein could
      deliver the recombinant Nef protein alone and notably by forming the noncovalent
      complexes with TurboFect, Pep-1 and Cady-2 as detected in western blotting.
      Moreover, intracellular uptake of Tat-Nef gene and subsequently its expression in
      mammalian cells was considerably higher than that for Nef gene. CONCLUSION: This
      data indicated that the Tat gene sequence could also increase the transfection of
      Nef gene in vitro. Generally, the Tat-Nef interaction led to enhance further gene
      expression and also protein delivery.

PMID- 27719634
TI  - Outcomes with Dronedarone in Atrial Fibrillation: What Differences Between Real
      World Practice and Trials? A Meta-Analysis and Meta-Regression Analysis.
AB  - Dronedarone was found to have divergent safety profiles in randomized controlled
      trials (RCT) in term of cardiac death and overall mortality. We decided to
      evaluate all available evidence on the cardiovascular safety of this drug. A
      systematic search was made of the MEDLINE and the Cochrane Central Register of
      Controlled Trials from January 2003 through April 2016 for RCT comparing
      dronedarone to placebo/active control, to provide the most accurate estimate of
      the effects of this agent and observational cohort studies (OBS) reporting
      clinical outcomes in patients treated with dronedarone, according to current
      guidelines, to obtain a real-life comparator for the findings summarized by RTC
      analysis. The literature search yielded 2335 papers and after careful review we
      identified 12 RCT and 7 OBS studies. RCT meta-analysis showed that, despite high
      heterogeneity, dronedarone was not associated with increased all-cause mortality
      [OR (Odds Ratio) 1.36, 95%CI (Confidence Interval) 0.79-2.33; p=0.732, I2=57.0%]
      or cardiovascular mortality [OR 1.51 95%CI 0.74-3.08; p=0.860, I2=64.4%]. OBS
      studies had a trend toward a better survival with respect to RCT [ES (Effect
      Size) 2.03, 95%CI 0.53-3.53 vs. ES 3.03, 95%CI 1.23-4.83; p=0.115], reaching the
      significance when restricted to the cardiovascular mortality [ES 0.52, 95%CI 0.36
      0.69 vs. ES 1.86, 95%CI 0.62-3.09; p<0.001]. Two variables, co-adiministration of
      digoxin and prevalence of non-permanent AF completely abolished the
      dishomogeneity among the analyzed RCT studies. In conclusion, use of dronedarone
      for prophylaxis of AF recurrences is not associated with an increased risk of
      death, either cardiovascular or total, and combination with digoxin should be
      avoided.

PMID- 27719635
TI  - Bile Acids as Novel Pharmacological Agents: The Interplay Between Gene
      Polymorphisms, Epigenetic Factors and Drug Response.
AB  - BACKGROUND: The field of bile acid research has become tremendously active. Bile
      acids have been shown to act as signaling molecules that are involved in many
      metabolic processes, but their role in carcinogenesis is also emerging. METHODS:
      The aim of this review was to summarize the present knowledge in the innovative
      field of bile acids pharmacology, to reveal the novel mechanisms of their action,
      particularly focusing on clinically relevant aspects, and to evaluate the role of
      both genetic and epigenetic variation in genes encoding bile acid-activated
      receptors in determining the therapy outcome. RESULTS: Most effects of bile acids
      are mediated by both nuclear and G protein-coupled receptors. Three natural bile
      acids have already been registered for the use in humans, but various semi
      synthetic bile acid analogues with improved pharmacokinetic and pharmacodynamic
      properties have been developed, which opens up new avenues in pharmacotherapy.
      Many efforts have been made to evaluate the impact of nuclear receptors on inter
      individual variation in responses to drugs, since nuclear receptors are
      significant mediators between environmental stimuli and pharmacokinetics. Genetic
      variation of bile acid-activated receptors is associated with both benign and
      malignant diseases, in terms of disease risk and severity, but also with
      pharmacokinetics and therapy outcome. Furthermore, the activity of these
      receptors may be masked or amplified by epigenetic modifications. CONCLUSION:
      Both genetic and epigenetic factors may alter complex and intricate network of
      bile acid signaling pathways, contributing to the development of several
      metabolic and non-metabolic diseases and altered activities of drug-metabolizing
      enzymes and transporters. These polymorphisms and epigenetic modifications may
      also impact the effectiveness and pharmacokinetics of bile acid analogues, which
      must be taken into account during the development of these compounds as novel
      therapeutic agents.

PMID- 27719636
TI  - RNF5, DAB2 and Friends: Novel Drug Targets for Cystic Fibrosis.
AB  - BACKGROUND: Deletion of phenylalanine 508 is the most frequent mutation causing
      cystic fibrosis. It causes multiple defects: 1) misfolding of the protein causing
      retention at the ER (processing defect); 2) reduced channel activity (gating
      defect); 3) reduced plasma membrane residency time due to increased
      internalization rate and defective recycling. METHODS: Druggability of F508del
      CFTR was demonstrated by several studies. Correctors are molecules able to
      improve maturation and trafficking to the membrane of F508del- CFTR. Correctors
      could act as pharmacological chaperones or as proteostasis regulators.
      Pharmacological chaperones act directly on mutant CFTR, while proteostasis
      regulators modify the proteostasis environment leading to beneficial effects on
      CFTR maturation. RESULTS: The use of a single compound is not sufficient to
      promote a therapeutically relevant F508del-CFTR rescue. Drug therapy for CF will
      require combinations of correctors exploiting different mechanisms of action,
      i.e. pharmacological chaperones combined together or with a proteostasis
      regulator. CONCLUSION: Development of more effective CF drugs could therefore
      rely on a better understanding of the molecular events underlying CFTR
      processing/degradation. This review will focus on most promising pathways and
      related targets for the development of novel CF pharmacotherapies.

PMID- 27719638
TI  - Targeting Signalling Pathways in Hepatocellular Carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) represents the most common malignant
      liver tumor in humans, which incidence and mortality have increased in Europe and
      United States in the last years. Most patients are diagnosed at an advanced
      stage, when it is not amenable to curative therapies, so there is an urgent need
      for new, more effective therapeutic tools and strategies. The molecular
      mechanisms of hepatocarinogenesis and HCC progression have been increasingly
      understood with intense research in recent years. METHODS: The goal of this work
      is to discuss the different signalling pathways as important potential
      therapeutic targets. RESULTS: Disruption of pathways known to play roles in HCC,
      such as Wnt/beta-catenin, Hedgehog, RAF/MEK/ERK, tryosine kinase receptor-related
      pathway, Met-HGF, VEGF/ VEGF and ROR signalling pathways may be seminal for liver
      oncogenesis. CONCLUSION: This review reveals that oncogenes, especially microRNAs
      that are conserved across species and interfere with signalling pathways might be
      used as promising strategies for halting or reversing the progression of HCC.

PMID- 27719637
TI  - Targeting Notch as a Therapeutic Approach for Human Malignancies.
AB  - BACKGROUND: Notch is a multifaceted protein that plays a fundamental role in
      fetal development and tissue homeostasis by directing many cellular functions,
      including cell growth and differentiation, cell fate determination and regulation
      of stem cells maintenance. The Notch family consists of four receptors (Notch 1
      4) and five ligands (Jagged1-2 and Delta-like 1-3-4) widely expressed in human
      tissues. Given the crucial contribution of Notch signaling in many physiological
      processes, it is not surprising that a variety of human malignancies is
      characterized by a dysregulation of one or more components of this pathway.
      METHODS: In this review, we are going to provide a broad overview on the role of
      Notch pathway in solid and hematological malignancies and a survey on possible
      Notch-directed therapeutic strategies. RESULTS: We present the most recent
      findings indicating that Notch signaling dysregulation in human cancers may be
      due to genetic and epigenetic alterations or to the interactions with other
      oncogenic pathways. Furthermore, Notch activity may have an oncogenic or a tumor
      suppressor effect. Finally, we describe the latest preclinical and clinical
      studies concerning the different pharmacological approaches targeting Notch.
      CONCLUSION: The provided evidence confirms the importance of Notch pathway in
      human malignancies indicating that a strong rationale exists for the development
      of a Notch-tailored therapy.

PMID- 27719639
TI  - Hedgehog Signaling Pathway as Genetic and Epigenetic Target in Ovarian Tumors.
AB  - BACKGROUND: Hedgehog signaling pathway is a developmental pathway mostly inactive
      in adult tissues, with the exception of stem cells. It is often found upregulated
      in various tumors, and associated with cancer stem cell maintenance. METHODS:
      This review focuses on different aspects of Hedgehog activation in tumors, with
      special emphasis on ovarian tumors and their treatment. RESULTS: Mutations in
      pathway components lead to a series of developmental malformations and syndromes.
      Aberrant activation of the pathway can be caused by mutations, noncanonical
      transcriptional regulation, or epigenetic changes. CONCLUSION: This pathway is an
      interesting target in cancer therapy, especially when combined with therapies
      targeting other signaling pathways. Combination therapy can be used to bypass
      resistance or to target cancer stem cells in a more efficient way.

PMID- 27719640
TI  - Casein Kinase II (CK2) as a Therapeutic Target for Hematological Malignancies.
AB  - BACKGROUND: Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging
      as a promising therapeutic target in cancer. Recent studies have revealed an
      important role for CK2 in tumorigenesis. High levels of CK2 are noted in many
      malignancies including leukemia. Use of CK2 inhibitors in various malignancies
      including breast, prostate, and lung cancer are being tested. Although many CK2
      inhibitors exist, only a few have emerged as selective inhibitors that are potent
      and effective. CX-4945 is a selective, orallybioavailable small molecule
      inhibitor, which has shown encouraging results in pre-clinical models of
      leukemia. METHODS: In this review we will elaborate on the structure and
      physiological function of the CK2 protein as well as its role in cancer. We will
      review, in depth, the role of CK2 in leukemia and its mechanisms of tumorigenesis
      via phosphorylation of the tumor suppressor protein Ikaros. We will discuss both
      the importance of Ikaros in leukemia suppression and the restoration of Ikaros'
      tumor suppressor function after CK2 inhibition by CX-4945 (a CK2-specific
      inhibitor). RESULTS: CK2 is an oncogene that is overexpressed in hematological
      malignancies. In high risk Pre-B ALL, CK2 phosphorylates Ikaros tumor suppressor
      and promotes leukemogenesis. Inhibition of CK2 using CX4945 restores Ikaros
      function and leads to anti leukemic effects in vitro and in pre-clinical leukemia
      models. CONCLUSION: CK2 is an attractive target in treatment of various cancers.
      Currently only a few specific CK2 inhibitors are available. Preclinical studies
      using CK2 inhibitor, CX4945 in high risk pediatric leukemias have shown promising
      results and warrants further testing in other types of leukemia.

PMID- 27719641
TI  - Predictive Biomarkers for Linking Disease Pathology and Drug Effect.
AB  - BACKGROUND: Productivity in drug R&D continues seeing significant attrition in
      clinical stage testing. Approval of new molecular entities proceeds with slow
      pace specifically when it comes to chronic, age-related diseases, calling for new
      conceptual approaches, methodological implementation and organizational adoption
      in drug development. METHODS: Detailed phenotyping of disease presentation
      together with comprehensive representation of drug mechanism of action is
      considered as a path forward, and a big data spectrum has become available
      covering behavioral, clinical and molecular characteristics, the latter combining
      reductionist and explorative strategies. On this basis integrative analytics in
      the realm of Systems Biology has emerged, essentially aiming at traversing
      associations into causal relationships for bridging molecular disease specifics
      and clinical phenotype surrogates and finally explaining drug response and
      outcome. RESULTS: From a conceptual perspective bottom-up modeling approaches are
      available, with dynamical hierarchies as formalism capable of describing clinical
      findings as emergent properties of an underlying molecular process network
      comprehensively resembling disease pathology. In such representation biomarker
      candidates serve as proxy of a molecular process set, at the interface of a
      corresponding representation of drug mechanism of action allowing patient
      stratification and prediction of drug response. In practical implementation
      network analytics on a protein coding gene level has provided a number of example
      cases for matching disease presentation and drug molecular effect, and workflows
      combining computational hypothesis generation and experimental evaluation have
      become available for systematically optimizing biomarker candidate selection.
      CONCLUSION: With biomarker-based enrichment strategies in adaptive clinical
      trials, implementation routes for tackling development attrition are provided.
      Predictive biomarkers add precision in drug development and as companion
      diagnostics in clinical practice.

PMID- 27719642
TI  - Bonafide Targets of Deregulated microRNAs in Non-Small Cell Lung Cancer as Tool
      to Identify Novel Therapeutic Targets: A Review.
AB  - BACKGROUND: Non-small-cell lung cancer (NSCLC) is an aggressive neoplasm with a
      poor survival and novel therapies are urgently needed. The study of deregulated
      micro- RNAs (dereg-miRs) could constitute a strategy helping to detect specific
      genes playing a relevant role in the disease. Thus, the oncoproteins encoded by
      these genes could be exploited as novel therapeutic targets to be inhibited by
      small molecules, aptamers, or monoclonal antibodies. METHODS: The present review
      is focused on candidate genes having convincing biological evidences to be both
      bona fide targets for dereg-miRs and playing a role in NSCLC progression. These
      genes were evaluated according to the molecular pathway they belong. Moreover, in
      the attempt to provide an even broader list of candidate therapeutic targets for
      NSCLC, the full list of genes was analyzed using the online tool Interactome DB.
      RESULTS: Among the identified targets, some of them belong to p53 or MAP kinase
      signaling pathways, and others include caspases, MCL1, and BCL2L2 (playing a role
      in apoptosis), ZEB1, ZEB2, and USP25 (epithelial-to-mesenchymal transition),
      EZH2, SOX9, and HOXA5 (differentiation), Paxillin, LIMK1 and MTDH (cytoskeleton
      remodeling), and HDGF (angiogenesis). In addition, other targets, such as TIMP-2,
      PIM-1, and components of the IGF-signaling pathways were suggested following the
      interactome analysis. CONCLUSION: Studies on dereg-miRs helped to identify a set
      of genes whose encoded proteins could constitute candidates for future
      therapeutic approaches.

PMID- 27719643
TI  - Curcumin: An Effective Inhibitor of Interleukin-6.
AB  - Curcumin is apolyphenolic compound found in the dietary spice turmeric. Anti
      inflammatory effects of turmeric have been known for centuries and extensive
      studies over the last two to three decades revealed that curcumin is a key
      component in the anti-inflammatory effects of turmeric. Chronic inflammation is
      involved in the various pathologic states and curcumin demonstrated therapeutic
      effects in different inflammation-related diseases in various in vivo, in vitro
      and human based studies through regulation of different signaling molecules
      including transcription factors, chemokines, cytokines, tumor suppressor genes,
      adhesion molecules and microRNAs. Interleukin-6 (IL-6) plays important roles in
      various events during inflammation including regulation of antibody (and
      autoantibody) production, activation of T cells, differentiation of B cells,
      increased production of acute-phase proteins, hematopoiesis and angiogenesis,
      vascular permeability, and osteoclast differentiation. IL-6 is also involved in
      pathogenesis of different inflammatory diseases. There are numerous studies
      demonstrating association of down-regulation of IL-6 and/or inhibition of IL-6
      signaling with therapeutic effects of curcumin suggesting a role for modulation
      of IL-6 in anti-inflammatory effects of curcumin. Moreover, curcumin can be
      considered as potential therapy against IL-6 involved pathologic stats. In this
      narrative review, the in vitro, experimental and clinical studies that report
      association of IL-6 inhibition and therapeutic effects of curcumin are discussed.

PMID- 27719644
TI  - PPAR Agonists, Atherogenic Dyslipidemia and Cardiovascular Risk.
AB  - Peroxisome proliferator-activated receptors (PPAR) are implicated in the
      pathology of several metabolic diseases including obesity, diabetes, and
      atherosclerosis. PPAR agonists exert multiple lipid modifying actions which are
      beneficial to the prevention of atherosclerosis. Such benefits in lipid lowering
      actions include improvements in atherogenic dyslipidemia that seems to be
      particularly expressed in individuals at higher cardiovascular (CV) risk. In
      addition, the favorable effects of PPAR agonists on different cardio-metabolic
      parameters are established in several metabolic conditions, such as diabetes
      mellitus, insulin resistance, and heightened systemic inflammation. The goal of
      this review is to summarize the current evidence on PPAR agonists and their
      effects on atherogenic dyslipidemia and CV risk. The main findings indicate that
      PPAR agonists improve not only the lipid profile, but also lipoprotein
      subfractions associated with atherogenic dyslipidemia and other CV markers.
      However, future prospective studies are required to establish the long-term
      effects of such therapies on atherogenic lipoproteins and their benefit on CV
      outcomes.

PMID- 27719645
TI  - Impact of Statin Therapy on Plasma Vitamin D Levels: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: During recent years, treatment with statins has been suggested to
      induce several effect on bone status and vitamin D metabolism, interpreted as
      statins pleiotropic effects. Actually, the available data are not conclusive and
      the characteristics of this association remains unclear. AIM: The purpose of this
      meta-analysis was therefore to investigate the possible effect of statins therapy
      on vitamin D serum levels based on the reported results from RCTs and
      observational studies. METHODS: PubMed-Medline, SCOPUS, Web of Science and Google
      Scholar databases were searched to identify studies evaluating the impact of
      statins on plasma vitamin D concentrations from inception to September 16, 2015.
      A systematic assessment of bias in the included randomized controlled trials was
      performed using the Cochrane criteria. A random-effects model (using DerSimonian
      Laird method) and the generic inverse variance method were used for the
      heterogeneity of studies in terms of demographic characteristics of populations
      being studied and also differences in study design and type of statin being
      studied. Sensitivity analysis was conducted using the leave-one-out method.
      RESULTS: Following a multiple database search, 1422 published studies were
      identified; among these, 7 studies were found to be eligible and included in the
      systematic review and meta-analysis. Our meta-analysis of data from seven studies
      (including 5 RCTs) did not indicate any significant effect of statins treatment
      on plasma vitamin D levels. CONCLUSION: Further well-designed trials are
      necessary to confirm these results and to define better a possible relationship
      between statins and vitamin D levels.

PMID- 27719646
TI  - Therapeutic Potential of Phytochemicals in Combination with Drugs for
      Cardiovascular Disorders.
AB  - The incidence of cardiovascular disorders is increasing worldwide. Heart disease
      is the leading cause of death for both men and women. High blood pressure, high
      low-density lipoprotein cholesterol level, and smoking are key risk factors for
      heart disease. Other medical conditions such as diabetes, overweight, obesity and
      lifestyle can put people at a higher risk for coronary heart disease. The
      preventive measures based on the common drugs may help reduce the risk of
      cardiovascular diseases. The present review highlights the contributions of
      therapeutic potential of phytochemicals in management of cardiovascular diseases.
      However, the delivery efficiency of therapeutic agents can be enhanced in order
      to improve the efficacy of phytochemicals as a therapeutic agent. The oral
      administration of phytochemicals as therapeutic agents is a common approach. The
      review highlights the recent development of natural products for the
      complementary treatment of cardiovascular diseases. These findings indicate that
      the combination of therapeutic drugs and natural products may improve the
      treatment efficacy of therapeutic agents.

PMID- 27719647
TI  - Cardiovascular Toxicity of Cyclooxygenase Inhibitors and Promising Natur a l
      Substitutes.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are
      used for a wide variety of diseases including pain and inflammatory conditions
      such as osteoarthritis, rheumatoid arthritis, musculoskeletal disorders, and
      other comorbid complications. However, this group of drugs have undesirable
      effects such as peptic ulcer, bleeding and renal failure. Some of these side
      effects are associated with or caused by generation of oxidative stress.
      Following the withdrawal of a cyclo-oxygenase-2 (COX-2) inhibitor drug, rofecoxib
      (VIOXX(r)) due to cardiovascular complications, scientists suggested that natural
      COX-2 inhibitors might provide valuable alternatives to COX inhibitors. Although,
      most of medicinal plants reduce pain and inflammation in a similar manner to
      synthetic medications, however, they often have fewer side effects and are better
      tolerated. The present review other than focusing on cardiovascular and some
      other complications of NSAIDs, is trying to introduce the natural alternative
      remedies for these medications.

PMID- 27719648
TI  - Therapeutic Interventions for Advanced Glycation-End Products and its Receptor-
      Mediated Cardiovascular Disease.
AB  - Advanced glycation end products (AGEs) are heterogeneous group of molecules
      formed from nonenzymatic reaction of reducing sugars with amino group of
      proteins, lipids, and nucleic acid. Interaction of AGEs with its cell-bound
      receptor (RAGE) results in generation of oxygen radicals, nuclear factor kappa
      beta, proinflammatory cytokines and cell adhesion molecules, and is involved in
      the pathophysiology of cardiovascular diseases (CVD). Circulating soluble forms
      of RAGE (sRAGE) and endo-secretory RAGE (esRAGE) compete with RAGE for ligand
      binding and function as a decoy. This paper describes the endogenous and
      exogenous (high dietary AGEs, and cooking food under high dry heat, elevated pH,
      and longer period) sources of AGEs. AGERAGE- mediated CVD includes
      atherosclerosis, coronary artery disease, carotid artery disease, hypertension,
      peripheral vascular diseases, heart failure, cardiomyopathy, and microangiopathy.
      The therapeutic interventions with reduction in AGEs and RAGE, and elevation in
      sRAGE has been reported for the treatment of AGE-RAGEmediated CVD. Reduction in
      levels of AGEs can be achieved by reduction in consumption of food containing low
      amount of AGEs, cooking food at low temperature, moist heat, and shorter
      duration. AGE formation can be reduced with drugs, vitamins and stoppage of
      cigarette smoking. Statins, telmisartan, and curcumin have been used for
      suppression of RAGE. Statins, ACE-inhibitors, Rosiglitazone and vitamin D have
      been used to increase levels of sRAGE. Finally exogenous administration of sRAGE
      can be helpful in amelioration of CVD. In conclusion, AGE-RAGE-mediated CVD could
      be attenuated with reduction in consumption of AGEs, suppression of RAGE and
      elevation of sRAGE.

PMID- 27719649
TI  - Precision Medicine and a Patient-Orientated Approach: Is this the Future for
      Tracking Cardiovascular Disorders?
AB  - The latest statistics from the 2016 heart disease and stroke statistics update
      shows that cardiovascular disease is the leading global cause of death, currently
      accounting for more than 17.3 million deaths per year. Type II diabetes is also
      on the rise with out-of-control numbers. To address these pandemics, we need to
      treat patients using an individualized patient care approach, but simultaneously
      gather data to support the precision medicine initiative. Last year the NIH
      announced the precision medicine initiative to generate novel knowledge regarding
      diseases, with a near-term focus on cancers, followed by a longer-term aim,
      applicable to a whole range of health applications and diseases. The focus of
      this paper is to suggest a combined effort between the latest precision medicine
      initiative, researchers and clinicians; whereby novel techniques could
      immediately make a difference in patient care, but long-term add to knowledge for
      use in precision medicine. We discuss the intricate relationship between
      individualized patient care and precision medicine and the current thoughts
      regarding which data is actually suitable for the precision medicine data
      gathering. The uses of viscoelastic techniques in precision medicine are
      discussed and how these techniques might give novel perspectives on the success
      of treatment regimes of cardiovascular patients are explored. Thrombo-embolic
      stroke, rheumathoid arthritis and type II diabetes are used as examples of
      diseases where precision medicine and a patient-orientated approach can possibly
      be implemented. In conclusion it is suggested that if all role players work
      together by embracing a new way of thought in treating and managing
      cardiovascular disease and diabetes will we be able to adequately address these
      out-ofcontrol conditions.

PMID- 27719650
TI  - The Insular Cortex and Takotsubo Cardiomyopathy.
AB  - Transient left ventricular dysfunction in patients under emotional stress, also
      known as Takotsubo cardiomyopathy, has been recognized as a distinct clinical
      entity. Recent studies have supported the concept notion that the cardiovascular
      system is regulated by cortical modulation. A network consisting of the insular
      cortex (Ic), anterior cingulate gyrus, and amygdala plays a crucial role in the
      regulation of the central autonomic nervous system in relation to emotional
      stress such as anxiety, fear and sadness. Because the Ic is located in the region
      of the middle cerebral arteries, its structure tends to be exposed to a higher
      risk of cerebrovascular disease. Ic damage has been associated with myocardial
      injury, increased brain natriuretic peptide, and the incidence of Takotsubo
      cardiomyopathy. Because Ic damage has been associated with increased sympathetic
      nervous system activity, Ic damage is suggested to have a pivotal role in the
      pathophysiology of Takotsubo cardiomyopathy. In this review, we focus on the role
      of the Ic as a mediator for the cardiovascular system in relation to emotional
      stress, and we summarizes the current knowledge on the relationships between the
      Ic and Takotsubo cardiomyopathy.

PMID- 27719651
TI  - Effect of Sibutramine on Plasma C-Reactive Protein, Leptin and Adipon ectin
      Concentrations: A Systematic Review and Meta-Analysis of Randomized Contr olled
      Trials.
AB  - Sibutramine is an anti-obesity medication whose effects on weight loss have been
      widely explored. Moreover, limited number of studies also evidenced its
      correlates on adipokines and proinflammatory markers; however, their results have
      not been conclusive. Hence, a systematic review and meta-analysis of available
      evidence was conducted in order to calculate the effect size of sibutramine
      therapy on C-reactive protein (CRP), leptin and adiponectin concentrations. Seven
      randomized clinical trials with a total of 601 subjects met the eligibility
      criteria. Random effect meta-analysis evidenced a significant decrease in plasma
      levels of CRP and leptin (weighted mean difference [WMD] -15.58%, 95% confidence
      interval [95%CI]: -28.84, -2.33, p=0.021 and WMD -9.25, 95%CI: -15.73, -2.78,
      p=0.005, respectively) and increase of adiponectin (WMD 9.86%, 95%CI: 1.76,
      17.96, p=0.017) following sibutramine therapy. Subgroup analysis showed a greater
      CRP-lowering effect of sibutramine with doses <15 mg/day (WMD -17.26%, 95%CI: 
      31.02, -3.5, p=0.014) compared with doses .15 mg/day (WMD 6.01%, 95%CI: -43.38,
      55.40, p=0.811). In meta-regression analysis, changes in CRP were found to be
      independent of baseline or percentage change in body mass index. These results
      suggest a significant improvement of plasma CRP, leptin and adiponectin levels
      following treatment with sibutramine. Possible impacts and relevance of these
      alterations on cardiovascular risk profile remain to be clarified, especially in
      post-hoc analyses of sibutramine outcome trials among people without pre-existing
      cardiovascular disease.

PMID- 27719652
TI  - Non-Invasive Assessment of Liver Injury in Non-Alcoholic Fatty Liver Disease: A
      Review of Literature.
AB  - NAFLD (Non-Alcoholic Fatty Liver Disease) is an increasingly significant public
      health issue, regarded as the most relevant liver disease of the twenty-first
      century. Approximately 20%-30% of NAFLD subjects develop a NASH (Non-Alcoholic
      Steato-Hepatitis), a condition which can potentially evolve to liver cirrhosis
      and hepatocellular carcinoma. For these reasons a proper evaluation of liver
      damage is a key point for diagnosis and prognosis and liver biopsy still remains
      the "gold standard" procedure both for discrimination between steatosis and
      steatohepatitis and assessment of the degree of liver fibrosis. Nonetheless,
      given it is an invasive, painful and costly procedure, a great research efforts
      have been made in order to develop non-invasive methods for the assessment of
      NAFLD presence and/or severity by serum markers and imaging techniques. In this
      review we aimed to perform a comprehensive review of the literature about
      strengths and weaknesses of the main tools available for the non-invasive
      assessment of NAFLD patients.

PMID- 27719653
TI  - Licochalcone B Arrests Cell Cycle Progression and Induces Apoptosis in Human
      Breast Cancer MCF-7 Cells.
AB  - BACKGROUND: Recent patent of licochalcone B (LCB) as an antiinflammatory agent
      has been developed. Emerging evidence shows that LCB may be a promising
      alternative compound with anti-cancer activities. However, the anticancer
      mechanism of LCB in MCF-7 cells has not been fully investigated. OBJECTIVE: We
      aimed to unearth the anti-cancer effect and mechanism of LCB in MCF-7 cells.
      METHOD: Cell proliferation activity and cell-cycle progression were determined by
      sulforhodamine B assay and flow cytometry, respectively. The mRNA and protein
      levels of cell cycle-related proteins and apoptosis-associated proteins were
      examined by RT-qPCR and western blot, respectively. Mitochondrial membrane
      potential (MMP) was measured by flow cytometry after JC-1 staining. RESULTS: We
      found that LCB inhibited MCF-7 cells proliferation in a concentration- and time
      dependent manner. Moreover, LCB-treatment led to S phase arrest in MCF-7 cells,
      which could be elucidated by the decreased mRNA and protein levels of Cyclin A,
      Cdk2 and Cdc25 A, and the increased protein level of p21. LCB also induced such
      apoptosis morphology as phosphatidylserine externalization, chromatin
      condensation and DNA fragmentation. Moreover, LCB led to the loss of MMP,
      resulting in the release of cytochrome C. The above apoptotic events were
      supported by the fact that LCB upregulated the mRNA and protein levels of Caspase
      3, Caspase 9 and Bax, and downregulated the mRNA and protein level of Bcl-2,
      which was triggered by the increased p53 protein level in LCB-treated MCF-7
      cells. CONCLUSION: These findings suggested that LCB could be a promising agent
      for treatment of human breast cancer.

PMID- 27719654
TI  - Leveraging Structural Diversity and Allosteric Regulatory Mechanisms of Protein
      Kinases in the Discovery of Small Molecule Inhibitors.
AB  - Protein kinases are versatile molecule switches that govern functional processes
      in signal transduction networks and regulate fundamental biological processes of
      cell cycle and organism development. The continuous growth of biological
      information and a remarkable breath of structural, genetic, and pharmacological
      studies on protein kinase genes have significantly advanced our knowledge of the
      kinase activation, drug binding and allosteric mechanisms underlying kinase
      regulation and interactions in signaling cascades.. Structural and biochemical
      studies of the genetic and molecular determinants of protein kinases binding with
      inhibitors have been the cornerstone of drug discovery efforts in clinical
      oncology leading to proliferation of effective anticancer therapies. Recent
      advances in understanding allosteric regulation of protein kinases have fueled
      unprecedented efforts aiming in the discovery of targeted and allosteric kinase
      inhibitors that can combat cancer mutants and are at the forefront of the
      precision medicine initiative in oncology. Despite diversity of regulatory
      scenarios underlying kinase functions, dimerization-driven activation is a common
      mechanism of allosteric regulation that is shared by many protein kinase
      families, most notably ErbB and BRAF kinases that play a central role in growth
      factor signaling and human disease. In this review, we focused on structural,
      biochemical and computational studies of the ErbB and BRAF kinases and discuss
      how diversity of the structural landscape for these kinase genes and dimerization
      dependent mechanisms of their regulation can be leveraged in the design and
      discovery of kinase inhibitors and allosteric modulators of kinase activation.
      The lessons from this analysis could inform discovery of specific targeted
      therapies and robust drug combinations for cancer treatment.

PMID- 27719655
TI  - Cardiac Biomarkers: Invasive to Non-invasive Assessments.
AB  - Cardiovascular disease (CVD) is a major threat to global health, estimated to be
      the cause 30 % (17.3 million in 2008) of deaths every year, and the number of
      deaths caused by CVD is expected to increase further, reaching 23.3 million by
      2030. Hence, there is a growing demand for simpler sample extraction, rapid
      screening results, and intervention of the subsequent analysis in emergency
      units. In this paper, we reviewed CVD biomarkers in blood- and saliva-based
      specimens. The history of cardiac biomarkers indicates that in the beginning,
      cardiac troponin I (cTnI) was a widely accepted 'gold standard' marker due to its
      high specificity and selectivity. Considering the advantages of salivary-based
      cardiac biomarkers, we examined correlations between non-invasive (salivary) and
      invasive (blood) diagnoses, and it was found that C-reactive protein (CRP)
      provides a better correlation. Despite the low abundance of salivary CRP, several
      reports displayed the detection limit down to pg/ml using existing technologies.
      Thus, salivary CRP has the potential to be used for future forefront diagnostics
      for the early assessment of cardiac risks.

PMID- 27719656
TI  - Oil Palm Defensin: A Thermal Stable Peptide that Restricts the Mycelial Growth of
      Ganoderma boninense.
AB  - Plant defensins are plant defence peptides that have many different biological
      activities, including antifungal, antimicrobial, and insecticidal activities. A
      cDNA (EgDFS) encoding defensin was isolated from Elaeis guineensis. The open
      reading frame of EgDFS contained 231 nucleotides encoding a 71-amino acid protein
      with a predicted molecular weight at 8.69 kDa, and a potential signal peptide.
      The eight highly conserved cysteine sites in plant defensins were also conserved
      in EgDFS. The EgDFS sequence lacking 30 amino acid residues at its N-terminus
      (EgDFSm) was cloned into Escherichia coli BL21 (DE3) pLysS and successfully
      expressed as a soluble recombinant protein. The recombinant EgDFSm was found to
      be a thermal stable peptide which demonstrated inhibitory activity against the
      growth of G. boninense possibly by inhibiting starch assimilation. The role of
      EgDFSm in oil palm defence system against the infection of pathogen G. boninense
      was discussed.

PMID- 27719657
TI  - GENIUS In Silico Screening Technology for HCV Drug Discovery.
AB  - The various reported in silico screening protocols such as molecular docking are
      associated with various drawbacks as well as benefits. In molecular docking, on
      interaction with ligand, the protein or receptor molecule gets activated by
      adopting conformational changes. These conformational changes cannot be utilized
      to predict the 3D structure of a protein-ligand complex from unbound protein
      conformations rigid docking, which necessitates the demand for understanding
      protein flexibility. Therefore, efficiency and accuracy of docking should be
      achieved and various available/developed protocols may be adopted. One such
      protocol is GENIUS induced-fit docking and it is used effectively for the
      development of anti-HCV NS3-4A serine protease inhibitors. The present review
      elaborates the GENIUS docking protocol along with its benefits and drawbacks.

PMID- 27719660
TI  - Neuroprotective and Neurotoxic Implications of alpha7 Nicotinic Acetylcholine
      Receptor and Abeta Interaction: Therapeutic Options in Alzheimer's Disease.
AB  - BACKGROUND: Alzheimer's disease, a neurodegenerative disorder, is characterized
      by accumulation of amyloid beta (Abeta) plaques, neurofibrillary tangles and loss
      of cholinergic neurons. LITERATURE REVIEW: The localization of Abeta plaques
      particularly in the cholinergic neuron-rich areas has led to the discovery that
      Abeta binds to alpha7 nicotinic acetylcholine receptors (nAChRs) with very high
      affinity. This discovery has led to extensive exploration of the possible
      outcomes of this binding, ranging from the subcellular signaling pathways to its
      effects on behavioral and cognitive functions. Intriguingly, there are
      conflicting reports about the effects of this Abeta and alpha7 nAChR interaction;
      a few studies report a neuroprotective role of this interaction while others
      claim that it is neurotoxic. CONCLUSION: This review focuses on the neurotoxic
      and neuroprotective effects of Abeta and alpha7 nAChR interaction and its
      implications on different cell signaling pathways and other physiological
      functions. Moreover, the implications this interaction might have on Alzheimer's
      disease therapy are also discussed.

PMID- 27719659
TI  - Cardioprotective Effects of the Polyphenol Hydroxytyrosol from Olive Oil.
AB  - BACKGROUND: The Mediterranean diet includes olive oil as its primary source of
      fat. This diet is frequently associated to longevity and a lower incidence of
      chronic diseases due to its biological activities and health effects. Apart from
      oleic acid, olive oil contains many bioactive components including polyphenols
      that have been reported to exert antioxidant and anti-inflammatory activities.
      Polyphenols may almost in part be responsible for the protective effects against
      cardiovascular diseases associated with olive oil. OBJECTIVE: To review and
      discuss the available literature on hydroxytyrosol effects as a cardioprotective
      agent. Moreover, we also discuss the chemistry, nutritional aspects and
      bioavailability of hydroxytyrosol. RESULTS: Hydroxytyrosol is one of the major
      phenolic compounds in olive oil and has demonstrated strong radical-scavenging
      properties. Several studies have been performed in order to look further into the
      effects of the polyphenol hydroxytyrosol in relation to cardiovascular events and
      illnesses in animal trials and in vitro. However, no clinical trials have focused
      on the specific action of hydroxytyrosol and cardiovascular diseases, although
      some are being undertaken to look at olive oil or olive leaf extract properties.
      CONCLUSION: Hydroxytyrosol from olive oil exerts antioxidant, anti-inflammatory,
      anti-platelet aggregation and ati-atherogenic activities in in vitro and animal
      models. However, its possible therapeutic use in humans requires additional
      clinical trials.

PMID- 27719658
TI  - Aspirin Intolerance: Experimental Models for Bed-to-Bench.
AB  - Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it
      sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory
      disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin
      intolerance) are also observed in patients with food-dependent exercise-induced
      anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU).
      However the target and the mechanism of the aspirin intolerance are still
      unknown. There is no animal or cellular model of AERD, because its
      pathophysiological mechanism is still unknown, but it is thought that inhibition
      of cyclooxygenase by causative agents leads to an increase of free arachidonic
      acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke
      airway smooth muscle constriction and asthma symptoms. As the bed-tobench
      approach, to confirm the clinical discussion in experimental cellular models, we
      have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a
      rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD),
      enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction
      of cysLTs production in the absence of inflammatory activation. Since this
      suggests that all inflammatory cells with activation of prostaglandin and cysLT
      metabolism should respond to NSAIDs, and then I have concluded that aspirin
      intolerance should be separated from subsequent bronchoconstriction. Evidence
      about the cellular mechanisms of NSAIDs may be employed for development of in
      vitro AERD models as the approach from bench-to-bed.

PMID- 27719661
TI  - Neuroprotective Effects of Ellagitannins: A Brief Review.
AB  - BACKGROUND: Neurodegenerative diseases are increasingly inevitable as the
      population gets older, with enormous socio-economic costs. The World Health
      Organization (WHO) has reported that by 2040, neurodegenerative diseases will
      overtake cancer to become the second leading cause of death, after cardiovascular
      disease. OBJECTIVE: Herein, this review outlines the neuroprotective effects and
      clinical implications of ellagitannins, a class of hydrolysable tannins, for the
      management and treatment of neurodegenerative disorders. RESULTS: Recent
      investigations suggest that the combination of genes and environmental toxins may
      contribute to the risk of developing neurodegenerative disorders. Thus,
      intervention strategies aimed at reducing exposure to risk factors such as life
      style, smoking, diet, vitamin deficiencies, chemical exposure and pollution are
      warranted. Modulation of dietary components including ellagitannins, as a
      therapeutic strategy to slow down or attenuate the progression of neuronal
      degeneration has become a focus of interest in the last few decades. CONCLUSION:
      Polyphenolic plant phytochemicals and ellagitannins in particular, contain an
      array of neuroprotective properties useful to improve human health and protect
      against neurodegeneration.

PMID- 27719663
TI  - Astrocytes as an HIV Reservoir: Mechanism of HIV Infection.
AB  - If we have any hope of achieving a cure for HIV infection, close attention to the
      cell types capable of getting infected with HIV is necessary. Of these cell
      types, astrocytes are the most ideal cell type for the formation of such a
      reservoir. These are long-lived cells with a very low turnover rate and are found
      in the brain and the gastrointestinal tract. Although astrocytes are evidently
      resistant to infection of cell-free HIV in vitro, these cells are efficiently
      infected via cell-tocell contact by which immature HIV virions bud off
      lymphocytes and have the ability to directly bind to CXCR4, triggering the
      process of fusion in the absence of CD4. In this review, we closely examine the
      evidence for HIV infection of astrocytes in the brain and the mechanisms for
      viral entry and regulation in this cell type, and discuss an approach for
      controlling this viral reservoir.

PMID- 27719664
TI  - Overview on the Tricks of HIV Tat to Hit the Blood Brain Barrier.
AB  - HIV infection among AIDS patients is associated with dysfunctions in the central
      nervous system (CNS) at the late stages of the disease. HIV Tat protein is
      released extracellularly from the productively infected cells and play important
      role in successful HIV replication and activates the neighboring uninfected cells
      in the bystander fashion. The structural flexibility of Tat protein is one of the
      unique features, responsible for the diverse functions. The RNA binding ability
      and interacting domains are very important characteristic of the HIV-Tat protein.
      HIV Tat protein adversely affects the integrity of the blood brain barrier by a
      variety of mechanisms. Such compromise in the integrity of the blood brain
      barrier could affect the neuro-immune interactions within the brain, which
      results to the neuroinflammation.

PMID- 27719665
TI  - Plastid Molecular Pharming II. Production of Biopharmaceuticals by Plastid
      Transformation.
AB  - BACKGROUND: Higher plants have been used in medicine throughout human history.
      METHOD: While traditional medicinal uses relied on compounds produced naturally
      by plants, recent advances have enabled the use of plant-based factories to
      produce diverse agents including pharmaceuticals, antibiotics, and vaccines. The
      genes responsible for the production of these substances can be either
      transiently expressed in plants or integrated into their nuclear genome or
      plastid genome (plastome) by genetic transformation. This review focuses on the
      application of plastid transformation of higher plants to produce
      biopharmaceuticals for human applications that are neither antibiotics nor
      vaccines. Plastid transformation has several advantages over nuclear
      transformation and represents a minimal risk of transgene contamination to the
      environment via pollen grains because plastid genes are in most species normally
      maternally inherited and thus absent from pollen. Other advantages of
      sitedirected plastid insertion via homologous recombination include strong gene
      expression due to the plastid genome's high copy number and resistance to
      silencing, and the ability to achieve multi-gene expression with a single
      insertion step. RESULTS: Compared to bacterial systems, plant-based bioreactors
      offer lower production costs, lower risks of human pathogen contamination, and
      the possibility of exploiting post-translational modification. CONCLUSION:
      Consequently, sustainable plant systems based on different species, plastids, and
      tissues could become an important source of added value in pharmaceutical
      production.

PMID- 27719666
TI  - Cannabis: A Treasure Trove or Pandora's Box?
AB  - BACKGROUND & OBJECTIVE: Cannabis is one of the earliest cultivated plants.
      Cannabis of industrial utility and culinary value is generally termed as hemp.
      Conversely, cannabis that is bred for medical, spiritual and recreational
      purposes is called marijuana. The female marijuana plant produces a significant
      quantity of bio- and psychoactive phytocannabinoids, which regained the spotlight
      with the discovery of the endocannabinoid system of the animals in the early
      90's. Nevertheless, marijuana is surrounded by controversies, debates and
      misconceptions related to its taxonomic classification, forensic identification,
      medical potential, legalization and its long-term health consequences. METHOD: In
      the first part, we provide an in-depth review of the botany and taxonomy of
      Cannabis. We then overview the biosynthesis of phytocannabinoids within the
      glandular trichomes with emphasis on the role of peculiar plastids in the
      production of the secreted material. We also compile the analytical methods used
      to determine the phytocannabinoid composition of glandular trichomes. In the
      second part, we revisit the psychobiology and molecular medicine of marijuana.
      RESULTS & CONCLUSION: We summarize our current knowledge on the recreational use
      of cannabis with respect to the modes of consumption, short-term effects, chronic
      health consequences and cannabis use disorder. Next, we overview the molecular
      targets of a dozen major and minor bioactive cannabinoids in the body. This helps
      us introduce the endocannabinoid system in an unprecedented detail: its up-todate
      molecular biology, pharmacology, physiology and medical significance, and beyond.
      In conclusion, we offer an unbiased survey about cannabis to help better weigh
      its medical value versus the associated risks.

PMID- 27719667
TI  - Plastid Molecular Pharming I. Production of Oral Vaccines via Plastid
      Transformation.
AB  - BACKGROUND: Vaccines produced in plants have opened up new opportunities in
      vaccination. OBJECTIVE: Among the various categories of vaccines, the recombinant
      vaccine is generally regarded as the most economical and safest type because it
      cannot cause disease and does not require large-scale cultivation of pathogens.
      Due to the low cost of their cultivation, plants may represent viable alternative
      platforms for producing subunit vaccines. Genetic engineering of plastids is the
      innovation of the last three decades and has numerous benefits when compared to
      nuclear transformation. Due to the high level of expression, oral vaccines
      produced in transplastomic plants do not have to be purified as they can be
      consumed raw, which, therefore, reduces the cost of preparation, transportation
      and handling of the vaccines. Oral vaccination also excludes the risk of other
      infections or contaminations, while compartmentation of the plant cell provides
      an excellent encapsulation to the antigen within the plastid. RESULTS &
      CONCLUSION: Herein we review the main biotechnological and immunological aspects
      of the progress achieved in the field of plastid derived edible vaccines during
      the last decade. As there is a public debate against genetically modified crops,
      the advantages and limitations of oral vaccines are also discussed.

PMID- 27719668
TI  - Chlorophylls and their Derivatives Used in Food Industry and Medicine.
AB  - BACKGROUND & OBJECTIVE: Thylakoids and chloroplasts harbor several vital
      metabolic processes, but are most importantly associated with photosynthesis. The
      undisturbed functioning of this process necessitates the ceaseless synthesis of
      photosynthetic pigments, including closed tetrapyrroles such as chlorophylls
      (Chls). Chls probably represent the most abundant natural pigment molecules which
      are via photosynthesis not only crucial for the autotrophic production of food
      sources for heterotrophic organisms but have also contributed to oxygen
      production essential for aerobic metabolism. This review first briefly discusses
      the physico-chemical properties, biosynthesis, occurrence, in vivo localization
      and roles of the different Chl pigments. Then we provide a detailed overview of
      their potential applications in the food industry and medicine. These include the
      use of Chls and their derivatives (different chlorophyllins) as food colorants
      (identified as E140 and E141 in the European Union). METHOD: Different sources
      used for industrial extraction as well as different factors influencing pigment
      stability during processing are also critically reviewed. The problems
      surrounding the nomenclature, the production and the composition of different
      chlorophyllin mixtures are also discussed. RESULTS & CONCLUSION: Finally, a
      comprehensive overview of the health benefits and potential medicinal
      applications of these pigments and the future directions of research in these
      fields are provided.

PMID- 27719669
TI  - Endocrine disruption: In silico perspectives of interactions of di-(2
      ethylhexyl)phthalate and its five major metabolites with progesterone receptor.
AB  - BACKGROUND: Di-(2-ethylhexyl)phthalate (DEHP) is a common endocrine disrupting
      compound (EDC) present in the environment as a result of industrial activity and
      leaching from polyvinyl products. DEHP is used as a plasticizer in medical
      devices and many commercial and household items. Exposure occurs through
      inhalation, ingestion, and skin contact. DEHP is metabolized to a primary
      metabolite mono-(2-ethylhexyl)phthalate (MEHP) in the body, which is further
      metabolized to four major secondary metabolites, mono(2-ethyl-5
      hydroxyhexyl)phthalate (5-OH-MEHP), mono(2-ethyl-5-oxyhexyl)phthalate (5-oxo
      MEHP), mono(2-ethyl-5-carboxypentyl)phthalate (5-cx-MEPP) and mono[2
      (carboxymethyl)hexyl]phthalate (2-cx-MMHP). DEHP and its metabolites are
      associated with developmental abnormalities and reproductive dysfunction within
      the human population. Progesterone receptor (PR) signaling is involved in
      important reproductive functions and is a potential target for endocrine
      disrupting activities of DEHP and its metabolites. This study used in silico
      approaches for structural binding analyses of DEHP and its five indicated major
      metabolites with PR. METHODS: Protein Data bank was searched to retrieve the
      crystal structure of human PR (Id: 1SQN). PubChem database was used to obtain the
      structures of DEHP and its five metabolites. Docking was performed using Glide
      (Schrodinger) Induced Fit Docking module. RESULTS: DEHP and its metabolites
      interacted with 19-25 residues of PR with the majority of the interacting
      residues overlapping (82-95 % commonality) with the native bound ligand
      norethindrone (NET). DEHP and each of its five metabolites formed a hydrogen
      bonding interaction with residue Gln-725 of PR. The binding affinity was highest
      for NET followed by DEHP, 5-OH-MEHP, 5-oxo-MEHP, MEHP, 5-cx-MEPP, and 2-cx-MMHP.
      CONCLUSION: The high binding affinity of DEHP and its five major metabolites with
      PR as well as a high rate of overlap between PR interacting residues among DEHP
      and its metabolites and the native ligand, NET, suggested their disrupting
      potential in normal PR signaling, resulting in adverse reproductive effects.

PMID- 27719670
TI  - Characterization of left and right atrial function in healthy volunteers by
      cardiovascular magnetic resonance.
AB  - BACKGROUND: Left and right atrial function show a different pattern in advanced
      age in order to maintain adequate ventricular filling. It has been shown that
      left atrial (LA) function has a prognostic value in a number of heart conditions.
      Cardiovascular magnetic resonance (CMR) provides high quality images of the left
      and right atria using high temporal resolution steady state free precession
      (SSFP) cine sequences. We used SSFP cines to characterize atrial function in
      healthy, normotensive, volunteers. METHODS: We measured maximum, preatrial
      contraction and minimum left and right atrial volumes in 120 healthy subjects
      after careful exclusion of cardiovascular abnormality (60 men, 60 women; 20
      subjects per age decile from 20 to 80 years). Data were generated from 3
      dimensional modeling, including tracking of the atrioventricular ring motion and
      time-volume curves analysis. With those measurements, all the usual parameters
      for left and right atrial function were calculated. RESULTS: Gender had
      significant influence on some parameters of left and right atrial conduit and
      booster pump function. Age significantly influenced the majority of parameters of
      both left and right atrial function, with typically lower reservoir and conduit
      functions and higher booster pump function, both in males and females belonging
      to older age groups. CMR normal ranges were modelled for clinical use with
      normalization, where appropriate, for body surface area and gender, displaying
      parameters with respect to age. CONCLUSIONS: CMR normal reference ranges for
      components of left and right atrial function are provided for males and females
      for a wide age range.

PMID- 27719671
TI  - Increasing the evidence base in journalology: creating an international best
      practice journal research network.
AB  - Biomedical journals continue to be the single most important conduit for
      disseminating biomedical knowledge. Unlike clinical medicine, where evidence is
      considered fundamental to practice, journals still operate largely in a 'black
      box' mode without sufficient evidence to drive their practice. We believe there
      is an immediate need to substantially increase the amount and quality of research
      by journals to ensure their practice is as evidence based as possible. To achieve
      this goal, we are proposing the development of an international 'best practice
      journal research network'. We invite journals and others to join the network.
      Such a network is likely to improve the quality of journals. It is also likely to
      address many unanswered questions in publication science, including peer review,
      which can provide robust and generalizable answers.

PMID- 27719672
TI  - Human sex hormone-binding globulin as a potential target of alternate
      plasticizers: an in silico study.
AB  - BACKGROUND: Currently, alternate plasticizers are used to replace phthalate
      plasticizers in children's toys, medical equipments and food packaging, due to
      the adverse effects of phthalate compounds on human health and laws prohibiting
      their use. Current information regarding the safety and potential adverse effects
      of alternate plasticizers is limited and recent studies have found alternate
      plasticizers to display similar characteristics to those observed in phthalate
      plasticizers. This study was undertaken to evaluate and predict the potential
      endocrine disrupting activity of the three most commonly used alternate
      plasticizers: di(2-ethylhexyl)terephthalate (DEHT), tris(2
      ethylhexyl)trimellitate (TOTM), and diisononyl hexahydrophthalate (DINCH) against
      human sex hormone-binding globulin (SHBG) using in silico approaches. MATERIALS
      AND METHODS: The crystal structure of human SHBG (Id: 1D2S) was retrieved from
      Protein Data Bank. PubChem database was searched for the structures of alternate
      plasticizers, DEHT, TOTM, and DINCH. Docking was performed using Glide
      (Schrodinger) Induced Fit Docking module. RESULTS: Induced Fit Docking of three
      alternate plasticizer compounds indicated that each of the three compounds fitted
      well into the steroid binding pocket of SHBG. Docking displays showed
      interactions of alternate plasticizers with 25-30 amino-acid residues of SHBG; 18
      20 amino residues overlapped between the natural ligand, DHT, and the three
      compounds (commonality of 82-91 %). The hydrogen-bonding interaction of the amino
      acid residue, Asn-82, of SHBG was also present in displays of DHT and all the
      three alternate phthalates. The binding affinity of all the three alternate
      phthalates was higher than DHT; maximum in DINCH followed by TOTM and DEHT.
      CONCLUSION: Our results suggested that the three alternate plasticizers have
      potential to engage the important interacting residues of SHBG and thus interfere
      in its steroid homeostatic function.

PMID- 27719673
TI  - Health care provider knowledge and routine management of pre-eclampsia in
      Pakistan.
AB  - BACKGROUND: Maternal mortality ratio is 276 per 100,000 live births in Pakistan.
      Eclampsia is responsible for one in every ten maternal deaths despite the fact
      that management of this disease is inexpensive and has been available for
      decades. Many studies have shown that health care providers in low and middle
      income countries have limited training to manage patients with eclampsia. Hence,
      we aimed to explore the knowledge of different cadres of health care providers
      regarding aetiology, diagnosis and treatment of pre-eclampsia and eclampsia and
      current management practices. METHODS: We conducted a mixed method study in the
      districts of Hyderabad and Matiari in Sindh province, Pakistan. Focus group
      discussions and interviews were conducted with community health care providers,
      which included Lady Health Workers and their supervisors; traditional birth
      attendants and facility care providers. In total seven focus groups and 26
      interviews were conducted. NVivo 10 was used for analysis and emerging themes and
      sub-themes were drawn. RESULTS: All participants were providing care for pregnant
      women for more than a decade except one traditional birth attendant and two
      doctors. The most common cause of pre-eclampsia mentioned by community health
      care providers was stress of daily life: the burden of care giving, physical
      workload, short birth spacing and financial constraints. All health care provider
      groups except traditional birth attendants correctly identified the signs,
      symptoms, and complications of pre-eclampsia and eclampsia and were referring
      such women to tertiary health facilities. Only doctors were aware that magnesium
      sulphate is recommended for eclampsia management and prevention; however, they
      expressed fears regarding its use at first and secondary level health facilities.
      CONCLUSION: This study found several gaps in knowledge regarding aetiology,
      diagnosis and treatment of pre-eclampsia among health care providers in Sindh.
      Findings suggest that lesser knowledge regarding management of pre-eclampsia is
      due to lack of refresher trainings and written guidelines for management of pre
      eclampsia and presentation of fewer pre-eclamptic patients at first and secondary
      level health care facilities. We suggest to include management of pre-eclampsia
      in regular trainings of health care providers and to provide management protocols
      at all health facilities. TRIAL REGISTRATION: NCT01911494.

PMID- 27719674
TI  - Age, environment, object recognition and morphological diversity of GFAP
      immunolabeled astrocytes.
AB  - BACKGROUND: Few studies have explored the glial response to a standard
      environment and how the response may be associated with age-related cognitive
      decline in learning and memory. Here we investigated aging and environmental
      influences on hippocampal-dependent tasks and on the morphology of an unbiased
      selected population of astrocytes from the molecular layer of dentate gyrus,
      which is the main target of perforant pathway. RESULTS: Six and twenty-month-old
      female, albino Swiss mice were housed, from weaning, in a standard or enriched
      environment, including running wheels for exercise and tested for object
      recognition and contextual memories. Young adult and aged subjects, independent
      of environment, were able to distinguish familiar from novel objects. All
      experimental groups, except aged mice from standard environment, distinguish
      stationary from displaced objects. Young adult but not aged mice, independent of
      environment, were able to distinguish older from recent objects. Only young mice
      from an enriched environment were able to distinguish novel from familiar
      contexts. Unbiased selected astrocytes from the molecular layer of the dentate
      gyrus were reconstructed in three-dimensions and classified using hierarchical
      cluster analysis of bimodal or multimodal morphological features. We found two
      morphological phenotypes of astrocytes and we designated type I the astrocytes
      that exhibited significantly higher values of morphological complexity as
      compared with type II. Complexity = [Sum of the terminal orders + Number of
      terminals] * [Total branch length/Number of primary branches]. On average, type I
      morphological complexity seems to be much more sensitive to age and environmental
      influences than that of type II. Indeed, aging and environmental impoverishment
      interact and reduce the morphological complexity of type I astrocytes at a point
      that they could not be distinguished anymore from type II. CONCLUSIONS: We
      suggest these two types of astrocytes may have different physiological roles and
      that the detrimental effects of aging on memory in mice from a standard
      environment may be associated with a reduction of astrocytes morphological
      diversity.

PMID- 27719675
TI  - Impact of HIV infection on the presentation, outcome and host response in
      patients admitted to the intensive care unit with sepsis; a case control study.
AB  - BACKGROUND: Sepsis is a prominent reason for intensive care unit (ICU) admission
      in patients with HIV. We aimed to investigate the impact of HIV infection on
      presentation, outcome and host response in sepsis. METHODS: We performed a
      prospective observational study in the ICUs of two tertiary hospitals. For the
      current analyses, we selected all patients diagnosed with sepsis within 24 hours
      after admission. Host response biomarkers were analyzed in a more homogeneous
      subgroup of admissions involving HIV-positive patients with pneumosepsis, matched
      to admissions of HIV-negative patients for age, gender and race. Matching was
      done by nearest neighbor matching with R package "MatchIt". RESULTS: We analyzed
      2251 sepsis admissions including 41 (1.8 %) with HIV infection (32 unique
      patients). HIV-positive patients were younger and admission of HIV-positive
      patients more frequently involved pneumonia (73.2 % versus 48.8 % of admissions
      of HIV-negative patients, P = 0.004). Disease severity and mortality up to one
      year after admission did not differ according to HIV status. Furthermore,
      sequential plasma levels of host response biomarkers, providing insight into
      activation of the cytokine network, the vascular endothelium and the coagulation
      system, were largely similar in matched admissions of HIV-positive and HIV
      negative patients with pneumosepsis. CONCLUSIONS: Sepsis is more often caused by
      pneumonia in HIV-positive patients. HIV infection has little impact on the
      disease severity, mortality and host response during sepsis.

PMID- 27719677
TI  - Community health workers' knowledge and practice in relation to pre-eclampsia in
      Ogun State, Nigeria: an essential bridge to maternal survival.
AB  - BACKGROUND: Pre-eclampsia is a leading cause of maternal and fetal morbidity and
      mortality worldwide. Early detection and treatment have been instrumental in
      reducing case fatality in high-income countries. To achieve this in a low-income
      country, like Nigeria, community health workers who man primary health centres
      must have adequate knowledge and skills to identify and provide emergency care
      for women with pre-eclampsia. This study aimed to determine community health
      workers' knowledge and practice in the identification and treatment of pre
      eclampsia, as they are essential providers of maternal care services in Nigeria.
      METHODS: This study was part of a multi-country evaluation of community treatment
      of pre-eclampsia. Qualitative data were obtained from four Local Government Areas
      of Ogun State, in south western Nigeria by focus group discussions (N = 15) and
      in-depth interviews (N = 19). Participants included a variety of community-based
      health care providers - traditional birth attendants, community health extension
      workers, nurses and midwives, chief nursing officers, medical officers - and
      health administrators. Data were transcribed and validated with field notes and
      analysed with NVivo 10.0. RESULTS: Community-based health care providers proved
      to be aware that pre-eclampsia was due to the development of hypertension and
      proteinuria in pregnant women. They had a good understanding of the features of
      the condition and were capable of identifying women at risk, initiating care, and
      referring women with this condition. However, some were not comfortable managing
      the condition because of the limitation in their 'Standing Order'; these
      guidelines do not explicitly authorize community health extension workers to
      treat pre-eclampsia in the community. CONCLUSION: Community-based health care
      providers were capable of identifying and initiating appropriate care for women
      with pre-eclampsia. These competencies combined with training and equipment
      availability could improve maternal health in the rural areas. There is a need
      for regular training and retraining to enable successful task-sharing with these
      cadres. TRIAL REGISTRATION: NCT01911494 .

PMID- 27719678
TI  - Community health worker knowledge and management of pre-eclampsia in rural
      Karnataka State, India.
AB  - BACKGROUND: In India, the hypertensive disorders of pregnancy and postpartum
      haemorrhage are responsible for nearly 40 % of all maternal deaths. Most of these
      deaths occur in primary health settings which frequently lack essential equipment
      and medication, are understaffed, and have limited or no access to specialist
      care. Community health care workers are regarded as essential providers of basic
      maternity care; and the quality of care they provide is dependent on the level of
      knowledge and skills they possess. However, there is limited research regarding
      their ability to manage pregnancy complications. This study aims to describe the
      current state of knowledge regarding pre-eclampsia and eclampsia among community
      health care workers (auxiliary nurse midwives, accredited social health
      activists, staff nurses) in northern Karnataka, India. Furthermore, this study
      describes the treatment approaches used by various cadres of community health
      workers for these conditions. The findings of this study can help plan focussed
      training sessions to build upon their strengths and to address the identified
      gaps. METHODS: Data were collected as part of a larger study aimed at assessing
      the feasibility of community-based treatment for pre-eclampsia. Eight focus group
      discussions were conducted in 2012-2013 in northern Karnataka State: four with
      staff nurses and auxiliary nurse midwives and four with accredited social health
      activists. In addition, twelve auxiliary nurse midwives and staff nurses
      completed questionnaires to explore their competence and self-efficacy in
      managing pre-eclampsia. Qualitative data were audio-recorded, transcribed
      verbatim and translated for thematic analysis using NVivo 10. RESULTS: Community
      health workers described their understanding of the origins of hypertension and
      seizures in pregnancy. Psychological explanations of hypertension were most
      commonly reported: stress, tension, and fear. The most common explanation for
      eclampsia was not receiving a tetanus vaccination. Despite some common
      misperceptions regarding aetiology, these community health workers demonstrated a
      good grasp of the potential consequences of hypertension in pregnancy. According
      to auxiliary nurse midwives and staff nurses, if hypertension was detected they
      encouraged rest, decreased salt intake, iron supplementation and tetanus
      vaccination. In addition, some staff nurses administered antihypertensives,
      MgSO4, or other anticonvulsants. All auxiliary nurse midwives had some awareness
      of MgSO4, but none had administered it themselves. CONCLUSIONS: This study showed
      that knowledge regarding the aetiology of pre-eclampsia was limited.
      Nevertheless, their basic knowledge and skills could be strengthened to more
      effectively manage the hypertensive disorders of pregnancy in their communities.
      TRIAL REGISTRATION: NCT01911494.

PMID- 27719679
TI  - Community perspectives on the determinants of maternal health in rural southern
      Mozambique: a qualitative study.
AB  - BACKGROUND: Mozambique has one of the highest rates of maternal mortality in sub
      Saharan Africa. The main influences on maternal health encompass social,
      economic, political, environmental and cultural determinants of health. To
      effectively address maternal mortality in the post-2015 agenda, interventions
      need to consider the determinants of health so that their delivery is not limited
      to the health sector. The objective of this exploratory qualitative study was to
      identify key community groups' perspectives on the perceived determinants of
      maternal health in rural areas of southern Mozambique. METHODS: Eleven focus
      group discussions were conducted with women of reproductive age, pregnant women,
      matrons, male partners, community leaders and health workers. Participants were
      recruited using sampling techniques of convenience and snow balling. Focus groups
      had an average of nine participants each. The heads of 12 administrative posts
      were also interviewed to understand the local context. Data were coded and
      analysed thematically using NVivo software. RESULTS: A broad range of political,
      economic, socio-cultural and environmental determinants of maternal health were
      identified by community representatives. It was perceived that the civil war has
      resulted in local unemployment and poverty that had a number of downstream
      effects including lack of funds for accessing medical care and transport, and
      influence on socio-cultural determinants, particularly gender relations that
      disadvantaged women. Socio-cultural determinants included intimate partner
      violence toward women, and strained relationships with in-laws and co-spouses.
      Social relationships were complex as there were both negative and positive
      impacts on maternal health. Environmental determinants included natural disasters
      and poor access to roads and transport exacerbated by the wet season and
      subsequent flooding. CONCLUSIONS: In rural southern Mozambique, community
      perceptions of the determinants of maternal health included political, economic,
      socio-cultural and environmental factors. These determinants were closely linked
      with one another and highlight the importance of including the local history,
      context, culture and geography in the design of maternal health programs.

PMID- 27719676
TI  - Nomenclature for renal replacement therapy and blood purification techniques in
      critically ill patients: practical applications.
AB  - This article reports the conclusions of the second part of a consensus expert
      conference on the nomenclature of renal replacement therapy (RRT) techniques
      currently utilized to manage acute kidney injury and other organ dysfunction
      syndromes in critically ill patients. A multidisciplinary approach was taken to
      achieve harmonization of definitions, components, techniques, and operations of
      the extracorporeal therapies. The article describes the RRT techniques in detail
      with the relevant technology, procedures, and phases of treatment and key aspects
      of volume management/fluid balance in critically ill patients. In addition, the
      article describes recent developments in other extracorporeal therapies,
      including therapeutic plasma exchange, multiple organ support therapy, liver
      support, lung support, and blood purification in sepsis. This is a consensus
      report on nomenclature harmonization in extracorporeal blood purification
      therapies, such as hemofiltration, plasma exchange, multiple organ support
      therapies, and blood purification in sepsis.

PMID- 27719681
TI  - Human resource constraints and the prospect of task-sharing among community
      health workers for the detection of early signs of pre-eclampsia in Ogun State,
      Nigeria.
AB  - BACKGROUND: The dearth of health personnel in low income countries has attracted
      global attention. Ways as to how health care services can be delivered in a more
      efficient and effective way using available health personnel are being explored.
      Task-sharing expands the responsibilities of low-cadre health workers and allows
      them to share these responsibilities with highly qualified health care providers
      in an effort to best utilize available human resources. This is appropriate in a
      country like Nigeria where there is a shortage of qualified health professionals
      and a huge burden of maternal mortality resulting from obstetric complications
      like pre-eclampsia. This study examines the prospect for task-sharing among
      Community Health Extension Workers (CHEW) for the detection of early signs of pre
      eclampsia, in Ogun State, Nigeria. METHODS: This study is part of a larger
      community-based trial evaluating the acceptability of community treatment for
      severe pre-eclampsia in Ogun State, Nigeria. Data was collected between 2011 and
      2012 using focus group discussions; seven with CHEWs (n = 71), three with male
      decision-makers (n = 35), six with community leaders (n = 68), and one with
      member of the Society of Obstetricians and Gynaecologists of Nigeria (n = 9). In
      addition, interviews were conducted with the heads of the local government
      administration (n = 4), directors of planning (n = 4), medical officers (n = 4),
      and Chief Nursing Officers (n = 4). Qualitative data were analysed using NVivo
      version 10.0 3 computer software. RESULTS: The non-availability of health
      personnel is a major challenge, and has resulted in a high proportion of facility
      based care performed by CHEWs. As a result, CHEWs often take on roles that are
      designated for senior health workers. This role expansion has exposed CHEWs to
      the basics of obstetric care, and has resulted in informal task-sharing among the
      health workers. The knowledge and ability of CHEWs to perform basic clinical
      assessments, such as measure blood pressure is not in doubt. Nevertheless, there
      were divergent views by senior and junior cadres of health practitioners about
      CHEWs' abilities in providing obstetric care. Similarly, there were concerns by
      various stakeholders, particularly the CHEWs themselves, on the regulatory
      restrictions placed on them by the Standing Order. CONCLUSION: Generally, the
      extent to which obstetric tasks could be shifted to community health workers will
      be determined by the training provided and the extent to which the observed
      barriers are addressed. TRIAL REGISTRATION: NCT01911494.

PMID- 27719680
TI  - Potential for task-sharing to Lady Health Workers for identification and
      emergency management of pre-eclampsia at community level in Pakistan.
AB  - BACKGROUND: An estimated 276 Pakistani women die for every 100,000 live births;
      with eclampsia accounting for about 10 % of these deaths. Community health
      workers contribute to the existing health system in Pakistan under the banner of
      the Lady Health Worker (LHW) Programme and are responsible to provide a
      comprehensive package of antenatal services. However, there is a need to increase
      focus on early identification and prompt diagnosis of pre-eclampsia in community
      settings, since women with mild pre-eclampsia often present without symptoms.
      This study aims to explore the potential for task-sharing to LHWs for the
      community-level management of pre-eclampsia and eclampsia in Pakistan. METHODS: A
      qualitative exploratory study was undertaken February-July 2012 in two districts,
      Hyderabad and Matiari, in the southern province of Sindh, Pakistan. Altogether 33
      focus group discussions (FGDs) were conducted and the LHW curriculum and training
      materials were also reviewed. The data was audio-recorded, then transcribed
      verbatim for thematic analysis using QSR NVivo-version10. RESULTS: Findings from
      the review of the LHW curriculum and training program describe that in the
      existing community delivery system, LHWs are responsible for identification of
      pregnant women, screening women for danger signs and referrals for antenatal
      care. They are the first point of contact for women in pregnancy and provide
      nutritional counselling along with distribution of iron and folic acid
      supplements. Findings from FGDs suggest that LHWs do not carry a blood pressure
      device or antihypertensive medications; they refer to the nearest public facility
      in the event of a pregnancy complication. Currently, they provide tetanus toxoid
      in pregnancy. The health advice provided by lady health workers is highly valued
      and accepted by pregnant women and their families. Many Supervisors of LHWs
      recognized the need for increased training regarding pre-eclampsia and eclampsia,
      with a focus on identifying women at high risk. The entire budget of the existing
      lady health worker Programme is provided by the Government of Pakistan,
      indicating a strong support by policy makers and the government for the tasks
      undertaken by these providers. CONCLUSION: There is a potential for training and
      task-sharing to LHWs for providing comprehensive antenatal care; specifically for
      the identification and management of pre-eclampsia in Pakistan. However, the
      implementation needs to be combined with appropriate training, equipment
      availability and supervision. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01911494.

PMID- 27719683
TI  - Community health worker knowledge and management of pre-eclampsia in southern
      Mozambique.
AB  - BACKGROUND: Mozambique has drastically improved an array of health indicators in
      recent years, including maternal mortality rates which decreased 63 % from 1990
      2013 but the rates still high. Pre-eclampsia and eclampsia constitute the third
      major cause of maternal death in the country. Women in rural areas, with limited
      access to health facilities are at greatest risk. This study aimed to assess the
      current state of knowledge and the regular practices regarding pre-eclampsia and
      eclampsia by community health workers in southern Mozambique. METHODS: This mixed
      methods study was conducted from 2013 to 2014, in Maputo and Gaza Provinces,
      southern Mozambique. Self-administered questionnaires, in-depth interviews and
      focus group discussions were conducted with CHWs, district medical officers,
      community health workers' supervisors, Gynaecologists-Obstetricians and matrons.
      Quantitative data were entered into a database written in REDCap and subsequently
      analyzed using Stata 13. Qualitative data was imported into NVivo10 for thematic
      analysis. RESULTS: Ninety-three percent of CHW had some awareness of pregnancy
      complications. Forty-one percent were able to describe the signs and symptoms of
      hypertension. In cases of eclampsia, CHWs reported to immediately refer the
      women. The vast majority of the CHWs surveyed reported that they could neither
      measure blood pressure nor proteinuria (90 %). Fewer reported confidence in
      providing oral antihypertensives (14 %) or injections in pregnancy (5 %). The
      other community health care providers are matrons. They do not formally offer
      health services, but assists pregnant women in case of an emergency. Regarding
      pre-eclampsia and eclampsia, matrons were unable to recognise these biomedical
      terms. CONCLUSIONS: Although CHWs are aware of pregnancy complications, they hold
      limited knowledge specific to pre-eclampsia and eclampsia. There is a need to
      promote studies to evaluate the impact of enhancing their training to include
      additional content related to the identification and management of pre-eclampsia
      and eclampsia.

PMID- 27719682
TI  - Nomenclature for renal replacement therapy in acute kidney injury: basic
      principles.
AB  - This article reports the conclusions of a consensus expert conference on the
      basic principles and nomenclature of renal replacement therapy (RRT) currently
      utilized to manage acute kidney injury (AKI). This multidisciplinary consensus
      conference discusses common definitions, components, techniques, and operations
      of the machines and platforms used to deliver extracorporeal therapies, utilizing
      a "machine-centric" rather than a "patient-centric" approach. We provide a
      detailed description of the performance characteristics of membranes, filters,
      transmembrane transport of solutes and fluid, flows, and methods of measurement
      of delivered treatment, focusing on continuous renal replacement therapies (CRRT)
      which are utilized in the management of critically ill patients with AKI. This is
      a consensus report on nomenclature harmonization for principles of extracorporeal
      renal replacement therapies. Devices and operations are classified and defined in
      detail to serve as guidelines for future use of terminology in papers and
      research.

PMID- 27719684
TI  - Morphological and molecular identification of cryptic species in the Sergentomyia
      bailyi (Sinton, 1931) complex in Sri Lanka.
AB  - The correct identification of sand fly vectors of leishmaniasis is important for
      controlling the disease. Genetic, particularly DNA sequence data, has lately
      become an important adjunct to the use of morphological criteria for this
      purpose. A recent DNA sequencing study revealed the presence of two cryptic
      species in the Sergentomyia bailyi species complex in India. The present study
      was undertaken to ascertain the presence of cryptic species in the Se. bailyi
      complex in Sri Lanka using morphological characteristics and DNA sequences from
      cytochrome c oxidase subunits. Sand flies were collected from leishmaniasis
      endemic and non-endemic dry zone districts of Sri Lanka. A total of 175 Se.
      bailyi specimens were initially screened for morphological variations and the
      identified samples formed two groups, tentatively termed as Se. bailyi species A
      and B, based on the relative length of the sensilla chaeticum and antennal
      flagellomere. DNA sequences from the mitochondrial cytochrome c oxidase subunit I
      (COI) and subunit II (COII) genes of morphologically identified Se. bailyi
      species A and B were subsequently analyzed. The two species showed differences in
      the COI and COII gene sequences and were placed in two separate clades by
      phylogenetic analysis. An allele specific polymerase chain reaction assay based
      on sequence variation in the COI gene accurately differentiated species A and B.
      The study therefore describes the first morphological and genetic evidence for
      the presence of two cryptic species within the Se. bailyi complex in Sri Lanka
      and a DNA-based laboratory technique for differentiating them.

PMID- 27719685
TI  - The role of standardized instruments in identifying older adults with alcohol
      problems.
AB  - Taylor et al. (2014) raise an important issue concerning the detection of alcohol
      problems in older adults. The authors identify a number of age-related factors
      playing a role in the detection of alcohol problems, such as stigma, the concept
      of alcohol use disorder diagnoses and their standardized assessment, and drinking
      levels. They list a comprehensive review of tools for assessing alcohol problems
      among older adults, including laboratory tests, questionnaires, and interviews.

PMID- 27719687
TI  - The Identification of Hereditary and Environmental Determinants of Frailty in a
      Cohort of UK Twins.
AB  - Our study examines the contribution of genetic and environmental factors (both
      shared and unique) to frailty, measured using the Rockwood Frailty Index (FI) in
      a sample of twins from the St Thomas' UK Adult Twin Registry. The FI was based on
      39 items of potential health deficit. Study participants were 3,375 volunteer
      adult twins (840 monozygotic and 802 dizygotic twin-pairs) 40.0-84.5 years old.
      First, we used structural equation modeling to estimate the relative contribution
      of genetics and of the shared and unique environment to variance in FI adjusted
      for age. In a second analysis, multiple linear regression was used to examine
      variance in FI as a function of father's occupational class (a component of
      shared environment and a measure of childhood socioeconomic status [SES]),
      adjusting for age, birth weight, marital status, and health behaviors (smoking,
      alcohol consumption, and physical activity). Statistical analyses were conducted
      using IBM SPSS(r) Version 22 software and Mx open source software. Findings
      showed that 45% (95% confidence intervals [CIs] 30-53%) of the inter-individual
      variation in FI was heritable and 52% (95% CIs 47-57%) was due to the
      individual's unique environment. Multiple linear regression also showed a small
      but statistically significant inverse association between father's occupational
      class and FI, mediated by one's own educational attainment and birth weight. Our
      results indicate that frailty is both genetically and environmentally determined.
      Thus, its prevention and management call for a multifaceted approach that
      includes addressing deleterious environmental factors, some of which, like
      childhood SES, may act across the life course.

PMID- 27719688
TI  - Perception of change in sexual activity in Alzheimer's disease: views of people
      with dementia and their spouse-caregivers.
AB  - INTRODUCTION: The onset of Alzheimer's disease (AD) affects couples'
      relationship. We investigated the perception of change and sexual satisfaction in
      spouse-caregivers and their partners diagnosed with AD. METHODS: We compared 74
      dyads of people with Alzheimer's disease (PwAD)/spouse-caregivers and 21 elderly
      dyads control. We assessed sexual satisfaction with Questionnaire on Sexual
      Experience and Satisfaction (QSES), cognition using a Mini-Mental State
      Examination (MMSE), disease severity using a Clinical Dementia Rating scale
      (CDR), awareness of disease with Assessment Scale of Psychosocial Impact of the
      Diagnosis of Dementia (ASPIDD), functionality with Pfeffer Functional Activities
      Questionnaire (FAQ), depressive symptoms with Cornell Scale for Depression in
      Dementia (CSDD), quality of life using a Quality of Life in Alzheimer's Disease
      Scale (QoL-AD), and burden using a Zarit Burden Interview (ZBI). RESULTS: We
      found differences between the perception and no perception of change in sexual
      activity of PwAD (p < 0.001), spouse-caregivers (p < 0.01), and controls (p <
      0.05). Moderate to severe sexual dissatisfaction was observed in 36.5% of PwAD,
      65% of spouse-caregivers, and 31% of controls. PwAD sexual satisfaction was
      related to cognitive impairment (p < 0.05). Spouse-caregivers sexual satisfaction
      was related to gender (p < 0.05) and the presence of sexual activity (p < 0.001).
      CONCLUSIONS: The perception of change with higher sexual dissatisfaction, were
      significant in PwAD and their spouse-caregivers, in comparison with couples of
      elderly without dementia.

PMID- 27719686
TI  - Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N
      neotetraose is well tolerated and shifts the intestinal microbiota.
AB  - The gut microbiota has been established as an important player influencing many
      aspects of human physiology. Breast milk, the first diet for an infant, contains
      human milk oligosaccharides (HMO) that shape the infant's gut microbiota by
      selectively stimulating the growth of specific bacteria, especially
      bifidobacteria. In addition to their bifidogenic activity, the ability of HMO to
      modulate immune function and the gut barrier makes them prime candidates to
      restore a beneficial microbiota in dysbiotic adults and provide health benefits.
      We conducted a parallel, double-blind, randomised, placebo-controlled, HMO
      supplementation study in 100 healthy, adult volunteers, consuming chemically
      produced 2'-O-fucosyllactose (2'FL) and/or lacto-N-neotetraose (LNnT) at various
      daily doses and mixes or placebo for 2 weeks. All participants completed the
      study without premature discontinuation. Supplementation of 2'FL and LNnT at
      daily doses up to 20 g was shown to be safe and well tolerated, as assessed using
      the gastrointestinal symptoms rating scale. 16S rRNA sequencing analysis showed
      that HMO supplementation specifically modified the adult gut microbiota with the
      primary impact being substantial increases in relative abundance of
      Actinobacteria and Bifidobacterium in particular and a reduction in relative
      abundance of Firmicutes and Proteobacteria. This study provides the first set of
      data on safety, tolerance and impact of HMO on the adult gut microbiota.
      Collectively, the results from this study show that supplementing the diet with
      HMO is a valuable strategy to shape the human gut microbiota and specifically
      promote the growth of beneficial bifidobacteria.

PMID- 27719689
TI  - COST-EFFECTIVENESS OF STRUCTURED EDUCATION IN CHILDREN WITH TYPE-1 DIABETES
      MELLITUS.
AB  - OBJECTIVES: Kids in Control OF Food (KICk-OFF) is a 5-day structured education
      program for 11- to 16-year-olds with type 1 diabetes mellitus (T1DM) who are
      using multiple daily insulin injections. This study evaluates the cost
      effectiveness of the KICk-OFF education program compared with the usual care
      using data from the KICk-OFF trial. METHODS: The short-term within-trial analysis
      covers the 2-year postintervention period. Data on glycated hemoglobin (HbA1c),
      severe hypoglycemia, and diabetic ketoacidosis (DKA) were collected over a 2-year
      follow-up period. Sub-group analyses have been defined on the basis of baseline
      HbA1c being below 7.5 percent (58.5 mmol/mol) (low group), between 7.5 percent
      and 9.5 percent (80.3 mmol/mol) (medium group), and over 9.5 percent (high
      group). The long-term cost-effectiveness evaluation has been conducted by using
      The Sheffield Type 1 Diabetes Policy Model, which is a patient-level simulation
      model on T1DM. It includes long-term microvascular (retinopathy, neuropathy, and
      nephropathy) and macrovascular (myocardial infarction, stroke, revascularization,
      and angina) diabetes-related complications and acute adverse events (severe
      hypoglycemia and DKA). RESULTS: The most favorable within-trial scenario for the
      KICk-OFF arm led to an incremental cost-effectiveness ratio (ICER) of L23,688
      (base year 2009) with a cost-effectiveness probability of 41.3 percent.
      Simulating the long-term complications using the full cohort data, the mean ICER
      for the base case was L28,813 (base year 2011) and the probability of the KICk
      OFF intervention being cost-effective at L20,000/QALY threshold was 42.6 percent,
      with considerable variation due to treatment effect duration. For the high HbA1c
      sub-group, the KICk-OFF arm was "dominant" (meaning it provided better health
      gains at lower costs than usual care) over the usual care arm in each scenario
      considered. CONCLUSIONS: For the whole study population, the cost-effectiveness
      of KICk-OFF depends on the assumption for treatment effect duration. For the high
      baseline HbA1c sub-group, KICk-OFF arm was estimated to be dominant over the
      usual care arm regardless of the assumption on the treatment effect duration.

PMID- 27719690
TI  - Impaired health status and increased incidence of diseases in Toxoplasma
      seropositive subjects - an explorative cross-sectional study.
AB  - The global seroprevalence of latent toxoplasmosis is estimated to be higher than
      30%. The presence of slowly dividing parasites in tissue cysts located mainly in
      immunoprivileged organs was long considered asymptomatic. Recently, many studies
      have shown that latent Toxoplasma infections could have serious impacts on human
      health. Here we ran a cross-sectional study in a population of 1486 volunteers.
      The results showed that 333 infected subjects scored worse than 1153 controls in
      28 of 29 health-related variables. Similarly, they reported higher rates of 77 of
      a list of 134 disorders reported by at least 10 participants of the study.
      Toxoplasmosis was associated most strongly with musculoskeletal (tau = 0.107, P <
      0.0005), followed by neurological (tau = 0.088, P < 0.0005), immune (tau = 0.085,
      p < 0.0005), metabolic (tau = 0.079, P < 0.0005), respiratory (tau = 0.068, P =
      0.0001), allergic (tau = 0.053, P = 0.004), digestive system (tau = 0.052, P =
      0.004) and mental health disorders (tau = 0.050, P = 0.008). Results of the
      present cohort study, along with the previous data from many case-control studies
      or ecological studies suggest that latent toxoplasmosis represents a large and so
      far underrated public health problem.

PMID- 27719691
TI  - A survey of paediatricians on the use of electrocardiogram for pre-participation
      sports screening.
AB  - : Aim The aim of the present study was to determine general paediatrician
      knowledge, practices, and attitudes towards electrocardiogram (ECG) screening in
      school athletes during pre-participation screening exam (PPSE). METHODS:
      Paediatricians affiliated with a tertiary children's hospital completed a survey
      about ECGs for PPSE. RESULTS: In total, 205/498 (41%) responded; 92% of the
      paediatricians did not include an ECG as part of PPSE; 56% were aware of a case
      in which a student athlete in their own community had died of sudden unexplained
      death; 4% had an athlete in their practice die. Only 16% of paediatricians
      perform all 12 American Heart Association recommended elements of the PPSE. If
      any of these screening elements are abnormal, 69% obtain an ECG, 36% an
      echocardiogram, and 30% restrict patients from sports activity; 73% of them refer
      the patient to a cardiologist. CONCLUSION: Most of the general paediatricians
      surveyed did not currently perform ECGs for PPSE. In addition, there was a low
      rate of adherence to performing the 12 screening elements recommended by the
      American Heart Association. They have trouble obtaining timely, accurate ECG
      interpretations, worry about potential unnecessary exercise restrictions, and
      cost-effectiveness. The practical hurdles to ECG implementation emphasise the
      need for a fresh look at PPSE, and not just ECG screening. Improvements in ECG
      performance/interpretation would be necessary for ECGs to be a useful part of
      PPSE.

PMID- 27719693
TI  - The most brutal of human skulls: measuring and knowing the first Neanderthal.
AB  - A fossilized skeleton discovered in 1856 presented naturalists with a unique
      challenge. The strange, human-looking bones of the first recognized Neanderthal
      confronted naturalists with a new type of object for which they had no readily
      available interpretive framework. This paper explores the techniques and
      approaches used to understand these bones in the years immediately following the
      discovery, in particular 1856-1864. Historians have previously suggested that
      interpretations and debates about Neanderthals hinged primarily on social,
      political and cultural ideologies. In this paper, I will argue that much of the
      scientific controversy surrounding the first recognized Neanderthal centred on
      questions of methodology and practice, and will demonstrate this through an
      exploration of the tools and approaches naturalists utilized in their
      examinations of the fossils. This will contribute to a growing historical
      recognition of the complex exchange between disciplines including geology,
      archaeology and comparative anatomy in the early study of fossil hominins, and
      provide a future framework for histories of Neanderthal debates in the twentieth
      century.

PMID- 27719694
TI  - The beginnings of human palaeontology: prehistory, craniometry and the 'fossil
      human races'.
AB  - Since the nineteenth century, hominid palaeontology has offered critical
      information about prehistoric humans and evidence for human evolution. Human
      fossils discovered at a time when there was growing agreement that humans existed
      during the Ice Age became especially significant but also controversial. This
      paper argues that the techniques used to study human fossils from the 1850s to
      the 1870s and the way that these specimens were interpreted owed much to the
      anthropological examination of Stone, Bronze, and Iron Age skeletons retrieved by
      archaeologists from prehistoric tombs throughout Europe. What emerged was the
      idea that a succession of distinct human races, which were identified using
      techniques such as craniometry, had occupied and migrated into Europe beginning
      in the Ice Age and continuing into the historic period. This marks a phase in the
      history of human palaeontology that gradually gave way to a science of
      palaeoanthropology that viewed hominid fossils more from the perspective of
      evolutionary theory and hominid phylogeny.

PMID- 27719695
TI  - A translation of the Linnaean dissertation The Invisible World.
AB  - This study presents the first translation from Latin to English of the Linnaean
      dissertation Mundus invisibilis or The Invisible World, submitted by Johannes
      Roos in 1769. The dissertation highlights Linnaeus's conviction that infectious
      diseases could be transmitted by living organisms, too small to be seen.
      Biographies of Linnaeus often fail to mention that Linnaeus was correct in
      ascribing the cause of diseases such as measles, smallpox and syphilis to living
      organisms. The dissertation itself reviews the work of many microscopists,
      especially on zoophytes and insects, marvelling at the many unexpected
      discoveries. It then discusses and quotes at length the observations of
      Munchhausen suggesting that spores from fungi causing plant diseases germinate to
      produce animalcules, an observation that Linnaeus claimed to have confirmed. The
      dissertation then draws parallels between these findings and the contagiousness
      of many human diseases, and urges further studies of this 'invisible world'
      since, as Roos avers, microscopic organisms may cause more destruction than
      occurs in all wars.

PMID- 27719696
TI  - Stories of stones and bones: disciplinarity, narrative and practice in British
      popular prehistory, 1911-1935.
AB  - This paper explores how three central figures in the field of British prehistory 
      Sir Arthur Keith, Sir Grafton Elliot Smith and Louis Leakey - deployed different
      disciplinary practices and narrative devices in the popular accounts of human bio
      cultural evolution that they produced during the early decades of the twentieth
      century. It shows how they used a variety of strategies, ranging from virtual
      witness through personal testimony to tactile demonstration, to ground their
      authority to interpret the increasingly wide range of fossil material available
      and to answer the bewildering variety of questions that could be asked about
      them. It investigates the way in which they positioned their own professional
      expertise in relation to fossil interpretation, particularly with regard to the -
      sometimes controversial - use they made of concepts, evidence and practices drawn
      from other disciplines. In doing so, they made claims that went beyond their
      original disciplinary boundaries. The paper argues that while none of these
      writers were able, ultimately, to support the wider claims they made regarding
      human prehistory, the nature of these claims deserves much closer attention,
      particularly with respect to the public role that historians of science can and
      should play in relation to present-day calls for greater interdisciplinarity.

PMID- 27719697
TI  - Introduction.

PMID- 27719698
TI  - Spain's magic mountain: narrating prehistory at Atapuerca.
AB  - The Sierra de Atapuerca in northern Spain is ranked among the most important
      excavation sites in human origins research worldwide. The project boasts not only
      spectacular hominid fossils, among them the 'oldest European', but also a fully
      fledged 'popularization industry'. This article interprets this multimedia
      industry as a generator of different narratives about the researchers as well as
      about the prehistoric hominids of Atapuerca. It focuses on the popular works of
      the three co-directors of the project. Juan Luis Arsuaga, Jose Maria Bermudez de
      Castro and Eudald Carbonell make deliberate use of a variety of narrative
      devices, resonant cultural references and strategies of scientific self
      commodification. All three, in different ways, use the history of science and of
      their own research project to mark their place in the field of human origins
      research, drawing on mythical elements to tell the story of the rise of a humble
      Spanish team overcoming all odds to achieve universal acclaim. Furthermore, the
      co-directors make skilful use of palaeofiction - that of Bjorn Kurten and Jean
      Auel, as well as writing their own - in order to tell gripping stories about
      compassion and solidarity in human prehistory. This mixture of nationalist and
      universalist narratives invites the Spanish audience to identify not just with
      'their ancestors' but also with the scientists, as objects and subjects of
      research become conflated through popularization.

PMID- 27719699
TI  - [Etiology, classification and systematic restorative treatment of tooth wear].
AB  - Tooth wear has complex and multi-factorial etiologies that result in the surface
      loss of dental hard tissues. Clinic prevention and restorative technology of
      tooth wear are challenge for dentists with the increasing numbers of population
      and the transition of disease age. From the etiology and classification of tooth
      wear, it is crucial to accurately assess and diagnose a patient presenting with
      tooth wear. Fluoride application, sealant and resin bonded restoration are
      beneficial to manage the mild tooth wear. For severe tooth wear, it is need to
      fabricate the diagnostic wax-up, and resin mock-up is also used to verify the
      occlusal relationship and vertical dimension increase, and then an interim
      restoration is also used to adapt the patient to the change of occlusion.
      Finally, by means of contemporary adhesive technique and min-invasive treatment,
      the dentist can reconstruct the shape of worn tooth, effectively restore the
      function of chewing and improve the appearance and pronounciation.

PMID- 27719700
TI  - [A ten-year clinical study of cracked teeth restored with glass ceramic crowns].
AB  - Objective: To evaluate the clinic performance of high strength glass ceramic
      crowns for the painful cracked teeth during a 10-year observation period.
      Methods: Forty-two posterior teeth from 36 patients were diagnosed as having a
      crack, biting painful and sensitivity to cold were selected in the Department of
      Prosthodontic, Institute and Hospital of Stomatology, Nanjing University Medical
      School. The lost-wax hot pressed glass ceramic crowns were bonded on the
      minimally invasive prepared teeth by modern adhesive technology. Patients were
      interviewed and went through clinic examination after one week, one month, and
      every six months. Results: The effectiveness of 42 glass ceramic crowns for
      cracked teeth was evaluated for a mean observation time over 10-year. At the
      first week, 29(81%) patients were free of pain, three still had sensitivity to
      cold and chewing pain, three still had sensitivity to cold, one had painful to
      cold and hot. After one month, two patients still had chewing pain, and one tooth
      needed endodontic treatment after six months. In 10 years, 2(5%) all ceramic
      crowns were broken, the other 40 restorations kept good clinical performances
      with a 10-year survival rate of 95%. Conclusions: The high strength glass ceramic
      crowns are very effective and successful in treating the cracked teeth and then
      keep the good mastication function and appearance.

PMID- 27719701
TI  - [Multidisciplinary treatment to build oral function and esthetics: a case
      report].

PMID- 27719702
TI  - [Multidisciplinary approaches for pink & white esthetics and function
      reconstruction of residual roots resulted from dental trauma].

PMID- 27719692
TI  - The animal trypanosomiases and their chemotherapy: a review.
AB  - Pathogenic animal trypanosomes affecting livestock have represented a major
      constraint to agricultural development in Africa for centuries, and their
      negative economic impact is increasing in South America and Asia. Chemotherapy
      and chemoprophylaxis represent the main means of control. However, research into
      new trypanocides has remained inadequate for decades, leading to a situation
      where the few compounds available are losing efficacy due to the emergence of
      drug-resistant parasites. In this review, we provide a comprehensive overview of
      the current options available for the treatment and prophylaxis of the animal
      trypanosomiases, with a special focus on the problem of resistance. The key
      issues surrounding the main economically important animal trypanosome species and
      the diseases they cause are also presented. As new investment becomes available
      to develop improved tools to control the animal trypanosomiases, we stress that
      efforts should be directed towards a better understanding of the biology of the
      relevant parasite species and strains, to identify new drug targets and
      interrogate resistance mechanisms.

PMID- 27719703
TI  - [Evaluation of therapeutic effect of virtual design for correcting facial
      asymmetry of skeletal Class III deformity].
AB  - Objective: To establish a computer-aided surgical simulation procedure based on
      the natural head position(NHP) for orthognathic surgery and to access the effect
      for correcting facial asymmetry for skeletal Class III deformity. Methods: Thirty
      five patients(male: 14 and female: 21, mean age: [21.5+/-2.3] years) of skeletal
      Class III deformity with facial asymmetry were included and divided into virtual
      group (16 patients) and control group(19 patients). The computer-aided surgical
      simulation procedure was used in the virtual group and the intermediate and final
      splints were fabricated using the rapid protyping technique. The traditional
      model surgery based on plaster casts was used in control group, and the splints
      were handmade. To evaluate the symmetry, three-dimensional(3D) photos were taken
      for all the patients before operation and 6 months after operation using the 3dMD
      face imaging system. Coordinate system was built based on mirror-original
      alignment method on the 3D photo. Thirteen soft tissue landmarks were marked on
      each 3D photo. The asymmetry index(AI) of those soft tissue landmarks was
      calculated. Results: There was no significant difference in the AI values between
      the two groups before surgery. Sixth month after operation, the mean AI values in
      the virtual group were (0.81+/-0.50) mm for subnasale, (1.01+/-0.80) mm for
      labiale superius, (1.94+/-1.30) mm for crista philtri, (1.60+/-1.20) mm for
      pogonion and (5.68+/-2.25) mm for gonion. The mean AI values in the control group
      were (1.49+/-1.10) mm for subnasale, (1.79+/-1.33) mm for labiale superius,
      (3.52+/-2.50) mm for crista philtri, (2.79+/-2.08) mm for pogonion and (8.43+/
      3.94) mm for gonion and those indexes were significantly different between the
      two groups(P<0.05). There was no significant difference in the AI values of the
      pronasale, alare, labiale inferius and cheilion between the two groups sixth
      month after operation. Conclusions: The introduced procedure of the virtual
      design based on the estimated NHP could more effectively correct the asymmetry
      deformity for the skeletal Class III patients.

PMID- 27719704
TI  - [Cone-beam CT evaluation of alveolar ridge modification subject to immediate
      implant with immediate loading and delayed loading].
AB  - Objective: To assess and compare the radiographic outcomes of immediate implant
      placement with two different loading timing. Methods: The involved cases were
      collected from Department of Implantology, Peking University School and Hospital
      of Stomatology. Patients recieved immediate implant placement during 2010 Aug to
      2012 Dec. The cases admitted delayed restoration program were assigned to Group
      I(18 patients with 21 implants), the cases admitted immediate restoration program
      were assigned to Group II (16 patients with 22 implants). Cone-beam CT(CBCT) was
      taken on the day after surgery and 6 months later. The thickness of the alveolar
      and the vertical alteration of marginal bone level were measured using the
      computer software subject to the CBCT. Wound closure was performed by single
      sutures in Group I. Provisional crown was delivered on the same day of implant
      insertion or the day after for Group II. Comparisons between baseline data and
      data from 6-month follow-up in both groups were conducted using paired t
      test(alpha=0.05). Results: The success rates of two groups were both 100%. The
      thickness got alteration after 6 months. The largest alteration position was at
      the 6 mm apical to the implant platform in Group I, which was (-0.75+/-1.31) mm.
      In Group II for each platform got similar alterations as -0.3 mm. There was no
      significant differences. Vertical alteration in two Groups showed significant
      difference, with (-0.73+/-1.88) mm(Group I) and (0.39+/-1.37) mm(Group II)
      respectively. Conclusions: Immediate restoration of dental implants which are
      placed in fresh extraction sockets has more advantages than delayed restoration
      protocol, for it shortens the course of treatment and preserves the alveolar
      bone.

PMID- 27719705
TI  - [Clinical study of the effect of free gingival graft and apically repositioned
      flap surgery on peri-implant keratinized gingival augmentation].
AB  - Objective: To compare and analyze the clinical outcomes of apically repositioned
      flap surgery and free gingival graft on keratinized gingival augmentation.
      Methods: Totally 30 partially edentulous patients treated with submerged implant
      surgery in mandibular molar area were recruited and divided into three groups:
      group 1(mean age: 41 years) and group 2 (mean age: 25 years) received free
      gingival graft 1 month after submerged implant surgery and second stage implant
      surgery3 months after submerged implant surgery; group 3(mean age: 44 years)
      received apically repositioned flap and second stage implant surgery 3 months
      after submerged implant surgery. The widths of keratinized gingiva were measured
      respectively at the time before the apically repositioned flap surgery/free
      gingival graft and 1 month, 6 months after the surgery. The thickness of
      keratinized gingiva was measured during the operation. Results: The widths of
      peri-implant keratinized gingiva of group 1 and group 2 were (3.1+/-1.2) mm and
      (3.5+/-1.0) mm 1 month after the free gingival graft surgery, (3.0+/-1.3) mm and
      (3.5+/-1.0) mm 6 months after the free gingival graft surgery, respectively. The
      widths of peri-implant keratinized gingiva in group 1 and group 2 demonstrated no
      statistically significant differences(P>0.05). The widths of peri-implant
      keratinized gingiva of group 3 was (2.6+/-0.5) mm 1 month after the apically
      repositioned flap surgery, (1.9+/-0.3) mm 6 months after the apically
      repositioned flap surgery, respectively. The widths of peri-implant keratinized
      gingiva(1 month and 6 months after the apically repositioned flap surgery) in
      group 3 showed statistically significant differences when compared with group 1
      and group 2(P=0.008, P=0.000). Conclusions: The implant area treated with free
      gingival graft or apically repositioned flap exhibited increased width of the
      keratinized gingiva. The implants treated with free gingival graft exhibited more
      increased width of the keratinized gingiva compared with those treated with
      apically repositioned flap. Age showed little impact on keratinized gingival
      augmentation.

PMID- 27719706
TI  - [Accuracy of three methods for the rapid diagnosis of oral candidiasis].
AB  - Objective: To explore a simple, rapid and efficient method for the diagnosis of
      oral candidiasis in clinical practice. Methods: Totally 124 consecutive patients
      with suspected oral candidiasis were enrolled from Department of Oral Medicine,
      Peking University School and Hospital of Stomatology, Beijing, China. Exfoliated
      cells of oral mucosa and saliva or concentrated oral rinse) obtained from all
      participants were tested by three rapid smear methods(10% KOH smear, gram-stained
      smear, Congo red stained smear). The diagnostic efficacy(sensitivity,
      specificity, Youden's index, likelihood ratio, consistency, predictive value and
      area under curve(AUC) of each of the above mentioned three methods was assessed
      by comparing the results with the gold standard(combination of clinical
      diagnosis, laboratory diagnosis and expert opinion). Results: Gram-stained smear
      of saliva(or concentrated oral rinse) demonstrated highest sensitivity(82.3%).
      Test of 10%KOH smear of exfoliated cells showed highest specificity(93.5%). Congo
      red stained smear of saliva(or concentrated oral rinse) displayed highest
      diagnostic efficacy(79.0% sensitivity, 80.6% specificity, 0.60 Youden's index,
      4.08 positive likelihood ratio, 0.26 negative likelihood ratio, 80% consistency,
      80.3% positive predictive value, 79.4% negative predictive value and 0.80 AUC).
      Conclusions: Test of Congo red stained smear of saliva(or concentrated oral
      rinse) could be used as a point-of-care tool for the rapid diagnosis of oral
      candidiasis in clinical practice. Trial registration: Chinese Clinical Trial
      Registry, ChiCTR-DDD-16008118.

PMID- 27719707
TI  - [Expression of secreted frizzled-related protein-1 in patient with oral submucous
      fibrosis].
AB  - Objective: To investigate the concentrations and clinical significance of
      secreted frizzled-related protein-1(SFRP1) insaliva and gingival crevicular fluid
      of patients with oral submucous fibrosis (OSF) as well as the expression of SFRP1
      in patients' OSF buccal mucosa. Methods: Twenty OSF patients aged 20 to 40 years
      old were recruited and randomly divided into two experimental groups, of which
      were triamcinolone acetonide group and combined triamcinolone acetonide and
      salvia miltiorrhiza group, respectively. Ten healthy volunteers matchable in sex
      and age with the patients were recruited as control group. Concentrations of
      SFRP1 in saliva and gingival crevicular fluid were detected by enzyme-linked
      immunosorbent assay before and after a continuous treatment of 4 weeks. The
      visual analogue scale(VAS) pain scores and opening size were also recorded. The
      expression of SFRP1 in samples from OSF patients' buccal mucosa was also detected
      using immunohistochemical method. SPSS 16.0 was applied to analyze the results of
      the experiments. Results: The concentrations of SFRP1 in saliva and gingival
      crevicular fluid before treatment were (105.8+/-27.6) ng/L and (84.7+/-33.2) ng/L
      in triamcinolone acetonide group, and (86.6+/-23.2) ng/L and (97.0+/-23.2) ng/L
      in combining group, which were both significantly lower(P<0.01) than that in
      normal group([153.0+/-32.8] ng/L and [157.5+/-31.1] ng/L), respectively. The
      positive expression rate of SFRP1 in OSF group(10%[2/20]) was significantly lower
      than that of the control group(10/10)(P<0.01). After the treatment for 4 weeks,
      the concentrations of SFRP1 increased to (141.2+/-35.3) ng/L and (130.6+/-31.3)
      ng/L in triamcinolone acetonide group, and to (148.5+/-65.9) ng/L and (123.0+/
      27.4) ng/L in combining group, which were both significantly higher than those of
      pre-treatment, respectively(P<0.01). Conclusions: The concentrations of SFRP1 in
      saliva and gingival crevicular fluid of OSF patients, which positively corelated
      to the expression of SFRP1 in OSF patients' buccal mucosa, were significantly
      lower than that of normal individuals and increased significantly after
      treatments of local injections of triamcinolone acetonide only or combined with
      salvia miltiorrhiza.

PMID- 27719708
TI  - [Authorization, translation, back translation and language modification of the
      simplified Chinese adult comorbidity-27 index].
AB  - Objective: To translate the adult comorbidity evaluation-27(ACE-27) index
      authored by professor JF Piccirillo into Chinese and for the purpose of assessing
      the possible impact of comorbidity on survival of oral cancer patients and
      improving cancer staging. Methods: The translation included the following steps,
      obtaining permission from professor Piccirillo, translation, back translation,
      language modification, adjusted by the advice from the professors of oral and
      maxillofacial surgery. The test population included 154 patients who were
      admitted to Peking University of Stomatology during March 2011. Questionnaire
      survey was conducted on these patients. Retest of reliability, internal
      consistency reliability, content validity, and structure validity were performed.
      Results: The simplified Chinese ACE-27 index was established. The Cronbach's
      alpha was 0.821 in the internal consistency reliability test. The Kaiser-Meyer
      Olkin (KMO) value of 8 items was 0.859 in the structure validity test.
      Conclusions: The simplified Chinese ACE-27 index has good feasibility and
      reliability. It is useful to assess the comorbidity of oral cancer patients.

PMID- 27719709
TI  - [Effect of three kinds of modelling of mandible on the finite element analysis of
      implant].
AB  - Objective: To investigate the effect of three types of material
      homogeneities(isotropy, transverse isotropy, and orthotropy) of mandible on the
      finite element analysis of implant. Methods: Three-dimensional model of complete
      mandible containing an implant was constructed and analyzed with isotropic,
      transversely isotropic, and orthotropic models, respectively. Results: The
      effective stress, tensile stress, and compressive stress of cortical bone of the
      orthogonal model were 1.2, 1.2, and 1.1 times larger than that of the isotropic
      model. The effective stress, tensile stress, and compressive stress of cancellous
      bone of the orthogonal model were 1.6, 2.6, and 3.3 times larger than that of the
      isotropic model. The effective strain, tensile strain, and compressive strain of
      cortical bone of the transversely isotropic model were 1.1, 1.0, and 1.1 times
      larger than that of the isotropic model. The effective strain, tensile strain,
      and compressive strain of cortical bone of the orthogonal model were 2.2, 1.8,
      and 1.7 times larger than that of the isotropic model. The stress and strain of
      cancellous bone increased when the material homogeneity changed from isotropy to
      transverse isotropy and to orthotropy. Moreover, in term of stress and strain
      distribution, the orthotropic modelling of mandible was most uniform followed by
      the transverse isotropy and the isotropy. Conclusions: In the finite element
      analysis of implant system, the orthotropic property of the mandible can not be
      neglected.

PMID- 27719711
TI  - [Summary of Conference on Oral Care Clinical Research].

PMID- 27719712
TI  - [The consensus of the diagnosis and treatment of lymphoplasmacytic
      lymphoma/Walderstrom macroglobulinemia in China (2016 version)].

PMID- 27719710
TI  - [Study on the influence of Wnt3a on osteogenetic differentiation ability of
      dental pulp stem cells induced by mineralizing medium].
AB  - Objective: To investigate the effects of Wnt3a protein on proliferation and
      osteogenic differentiation of human dental pulp stem cells(DPSC). Methods: Intact
      human permanent teeth extracted for orthodontic reasons were collected and used
      as study models. The biological effects of Wnt3a on DPSC were investigated using
      methyl thiazolyl tetrazolium(MTT), alkaline phosphatase(ALP) activity assay,
      alizarin red S staining and realtime fluorescence quantitative PCR. Osteogenic
      related gene expression of induced DPSC was examinedby using tests of bone
      sialoprotein(BSP), osteocalcin(OCN), collagen type I (COL-I) and Runt-related
      transcription factor 2(RUNX-2). Results: Wnt3a proteininduced an increase of cell
      growth and treatment of DPSC with Wnt3a induced a highest increase in cell growth
      at the concentration of 5 MUg/L. 5 MUg/L Wnt3a proteins combined with the
      osteogenic medium treatment caused up-regulated osteogenic differentiation, ALP
      activity and express of osteogenic-related genes of DPSC, and the ALP
      activity(0.47+/-0.04) was significantly stronger than the other groups(osteogenic
      medium: 0.39+/-0.05; 20 MUg/L: 0.34+/-0.03; 50 MUg/L: 0.27+/-0.07; 100 MUg/L:
      0.20+/-0.03). Conclusions: Exogenous Wnt3a protein treatment on DPSC could affect
      the proliferation and osteogenic differentiation.

PMID- 27719713
TI  - [The consensus of the diagnosis and treatment of mantle cell lymphoma in China
      (2016 version)].

PMID- 27719715
TI  - [How I treat newly diagnosed young patients with high risk diffuse large B cell
      lymphoma].

PMID- 27719714
TI  - [The consensus of the diagnosis and treatment of primary light chain amyloidosis
      in China (2016 version)].

PMID- 27719716
TI  - [Efficacy of GLIDE chemotherapy for patients with newly diagnosed advanced-stage
      or relapsed/refractory extranodal natural killer cell lymphoma].
AB  - Objective: To evaluate the efficacy of gemcitabine, asparaginase , ifosfamide,
      dexamethasone and etoposide (GLIDE) combination for patients with newly diagnosed
      advanced-stage or relapsed/refractory extranodal natural killer cell lymphoma
      (ENKL). Methods: Fourty-two newly diagnosed advanced-stage or relapsed/refractory
      ENKL were enrolled from March 2010 to March 2016. Patients were treated with
      GLIDE for median 3 (2-6) cycles. Complete response (CR) rate, early CR (after 2
      cycles) rate were evaluated after all treatment finished. Progression free
      survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and
      multivariate by Cox proportional hazards models. Results: Thirty-one (73.8%)
      patients achieved CR with 22 (52.4%) in early CR after 2 cycles of GLIDE, and 14
      underwent autologous stem cell transplantation (ASCT) after achieved CR. One year
      PFS and OS were 65.6% and 82.7%, 4 year PFS and OS were 48.2% and 63.1%,
      respectively, with a median PFS of 30.5 months. Multivariate analysis indicated
      ECOG score 0-1 and ASCT after CR were independent prognostic factors for less
      relapse and longer survival. Conclusion: GLIDE is an effective regiment for newly
      diagnosed advanced-stage and relapsed/refractory ENKL.

PMID- 27719717
TI  - [Efficacy of additional two cycles of rituximab administration for patients with
      diffuse large B-cell lymphoma in first remission].
AB  - Objective: To analyze the efficacy of additional two cycles of rituximab
      administration for Chinese patients with diffuse large B-cell lymphoma (DLBCL) in
      first complete remission (CR) after six cycles of standard 21-day rituximab plus
      cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP21). Methods:
      Retrospective analysis was performed in 351 patients with DLBCL diagnosed from
      March 2003 to March 2012. International Prognosis Index (IPI), Revised (R)-IPI
      and National Comprehensive Cancer Network (NCCN)-IPI were calculated for each
      patient. Patients were divided into GCB and non-GCB subtype according to Han's
      Classification. Progression-free survival (PFS) and overall survival (OS) were
      analyzed using Kaplan-Meier methods. Results: 282 (80.3%) patients achieved CR
      and 132 (46.8%) of 282 cases received additional two rituximab therapy. The other
      150 (53.2%) patients entered into observation on the intention of the patients.
      No significant difference was observed in baseline characteristics between the
      two groups. 3-year estimated PFS for additional rituximab group and observation
      group were 80.0% and 78.1% (P=0.334), while 3-year estimated OS were 89.7% vs.
      86.1% (P=0.452). By subgroup analysis, prolonged PFS were observed in R-IPI low
      risk and NCCN-IPI low-risk patients after additional two rituximab cycles.
      Conclusion: For patients with DLBCL in first remission after standard six cycles
      of R-CHOP21 regimen, additional two cycles of rituximab maintenance did not
      significantly improve the general prognosis, but low-risk subgroups of R-IPI and
      NCCN-IPI could benefit from this regimen.

PMID- 27719718
TI  - [Clinical features and outcomes: analysis of 9 cases of HIV-negtive plasmablastic
      lymphoma].
AB  - Objective: To evaluate the clinical features and outcomes of HIV-negtive
      plasmablastic lymphoma (PBL). Methods: Nine patients with HIV-negtive PBL were
      diagnosed and treated between January 2006 and January 2016. The clinical and
      follow-up data were analyzed retrospectively. Results: The median age was 56
      years (range 30-77 years) with a male-to-female ratio of 2?1. Nobody had
      underlying diseases associated with immunosuppression. Primary extra nodal
      diseases were observed in 7 cases and only 1 patient had oral involvement. Two
      patients were in earlystage and 7 in advanced stage by the Ann Arbor stage
      system. Ki-67 index was 60%-90% in the 9 cases, and 80% or higher in 7 cases.
      Epstein-Barr virus-encoded RNA expression (EBER) was detected in 4 cases, and 2
      of them were positive. Chemotherapy was documented in 9 patients, from which 8
      received the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-like
      regimens as the first-line chemotherapy and responses were observed in 5 (1
      complete, 4 partial responses). Three elderly patients were treated with CHOP
      combined with thalidomide, and 2 of them achieved partial responses. One patient,
      failed three chemotherapy regimens, accepted thalidomide combined with etopside
      and achieved stable disease for 10 months. One patient with early stage had
      disease-free survival of 61.9 months after treatment. The other eight patients
      experienced recurrence or progression after the first-line chemotherapy, and 6 of
      them died of disease progression within 2 years after the diagnosis. Conclusion:
      The HIV-negative PBL patients in this study did not have an apparent association
      with immunosuppression. Primary extra nodal diseases were common, but only 1
      patient had oral involvement. Most patients had advanced stage and poor
      prognosis. Effectiveness of thalidomide in the treatment of PBL deserves further
      investigation.

PMID- 27719719
TI  - [The clinical characteristics and outcomes of 16 Burkitt' s lymphoma with
      testicular involvement].
AB  - Objective: To analyze the clinical features and outcomes of Burkitt lymphoma with
      testicular involvement and study the efficiency of high dose methotrexate (HD
      MTX: 5-8g/m2) in those patients without radiation therapy. Method: Retrospective
      analysis was conducted in 16 Burkitt's lymphoma cases with testicular lymphoma
      involvement between Jan 2009 and Dec 2014. We followed the BCH-NHL-2009 protocol,
      modified from FAB LMB 89 combined with rituximab. All patients were enrolled in
      high-risk group (treated by Group C protocol). Results: Of 137 Burkitt lymphoma,
      16 (11.67% ) had testicular involvement. All the patients were in stage IV, the
      median age was 6.65 years (ranges: 2.25 to 13.5 years). 8 cases had bone marrow
      involvement, 9 with central nervous system involvement, 5 with bi-testicular
      involvement, 1 with EB virus infection (EBV-IgM+). The median follow-up was 31.8
      months (ranges: 0.5 to 79 months). During the study period, 2 cases died, 1 due
      to the disease relapse, the other one due to chemo-related dead. 1 had disease
      relapse 32 months after off treatment; the other 13 cases were all event free
      survival. 3-year OS was 87.5%, 3-year EFS was 72.9%. We also found the level of
      testosterone in ten adolescent were normal before and after chemotherapy.
      Conclusion: For the Burkitt lymphoma with testicular involvement, we abandon
      radiotherapy, and administer HD-MTX to lower the toxicity. The short-term
      survival is better, long-term survival still needs to be clarified.

PMID- 27719720
TI  - [IGHV mutational statue in patients with splenic marginal zone lymphoma].
AB  - Objective: To investigate the IGHV mutational status and its differences from
      Caucasian in splenic marginal zone lymphoma (SMZL). Methods: A retrospective
      study on 40 SMZL cases were performed to detect the V-D-J sequence of IGHV by
      plasmid cloning sequencing, comparing the data with the most homologous germ line
      V sequence in database, identifying the stereotype of patients through cluster
      analysis and alignment. The clinical and laboratory characteristics were compared
      between the patients with IGHV mutation and without mutations. Results: In SMZL
      patients, the proportion of IGHV mutations was 75%, consistent with data from
      Caucasian. In V region, the usage of V3-23 subtype was lower in Chinese patients
      compared with Caucasian (2.6% vs 18.0%, P=0.006), whereas the V2-70 subtype was
      used with high proportion (10.3% vs 0.8%, P=0.002). In D region, the D2-21 and D6
      13 gene were used frequently (17.9% vs 2.3%, P<0.001; 12.8% vs 3.8%, P=0.046).
      One new stereotype was found, and the SMZL-biased V1-2 gene was mostly used
      (25.6%). The levels of IgG and IgA were significantly increased in IGHV without
      mutations as compared with mutations [10.70 (5.28-15.50) g/L vs 12.90 (7.71
      23.50) g/L, 1.06 (0.21-3.13) g/L vs 1.66 (0.81-2.93) g/L, P=0.038, 0.040]. The
      only two 17p deletion patients were IGHV without mutaions. The progression free
      survival (PFS) was significantly prolonged in IGHV mutations (P=0.009), and there
      was no significant difference regarding to the overall survival between the two
      subgroups (P=0.430). Conclusion: The proportion of IGHV mutaions was similar to
      the data in Caucasian. There was disparity in the usage of V and D regions
      between Chinese and Caucasian, and the SMZL-biased V1-2 gene were used more
      frequently in Chinese patients. One new stereotype was identified. In the IGHV
      without mutations group, the levels of IgG and IgA were significantly increased.

PMID- 27719721
TI  - [T-bet in peripheral T-cell lymphoma].
AB  - Objective: To evaluate the expression of transcription factor T-bet (T-box
      expressed in T cells) and explore its effects on prognosis in peripheral T-cell
      lymphoma (PTCL). Methods: This study included 109 previously untreated patients
      diagnosed with PTCL in the pathology system at Peking Union Medical College
      Hospital from 2007 to 2013. Formalin-fixed, paraffin-embedded blocks and clinical
      information of these patients were collected. T-bet expression was examined by
      immunohistochemical stain, while its relationship with clinical feature and
      prognosis was analyzed. Results: 109 PTCL patients included 60 PTCL-not other
      specified (PTCL-NOS) cases and 18 NK/T-cell lymphoma. The positive rate of T-bet
      was 42.2% overall, 43.3% in PTCL-NOS and 44.4% in NK/T lymphoma. T-bet high
      expression wasn't correlated with OS in PTCL patients (P=0.586) by Kaplan-Meier
      analysis. Further stratification by pathological subgroup implied a correlation
      of T-bet high expression with better survival in NK/T lymphoma (P=0.004), but not
      in PTCL-NOS (P=0.309). Multivariate analysis confirmed that high ECOG score (>=2)
      was an independent predictor of overall survival (HR=5.907, 95%CI 2.399~14.549,
      P<0.001 ). Conclusion: T-bet was detected in several PTCL subgroups with
      diversities, which is positively correlated with overall survival in NK/T-cell
      lymphoma.

PMID- 27719722
TI  - [Anti-tumor effects of 13-cis-retinoic acid combined with interferon alpha-2b in
      animal model of mantle cell lymphoma].
AB  - Objective: To determine the anti-tumor effects of 13-cis-retinoic acid (13cRA)
      combined with interferonalpha-2b (IFNalpha-2b) in mantle cell lymphoma (MCL)
      animal model. Methods: The animal model of MCL was established by introducing
      Jeko-1 cell line into severe combined immunodeficiency disease mice. The
      successfully tumor-developed mice were assigned to different groups treated with
      negative control group (solvents), 13cRA (high dose: 200mg/kg; middle dose:
      100mg/kg; low dose: 50 mg/kg) alone, IFNalpha-2b alone or combination of
      different dose of 13cRA with IFNalpha-2b, and positive control group (bortezomib,
      rituximab, cyclophosphamide), respectively. Variations of tumor volume were
      observed regularly. The relative tumor proliferation rate and tumor inhibition
      rate were calculated. Immunohistochemistry stain was used to detect the Ki-67
      expression and TUNEL was applied to measure the apoptosis of tumor cells.
      Furthermore, the levels of Cyclin D1, caspase 9 and Rb protein were measured by
      Western-blot method. Results: 1 The relative tumor proliferation rates (T/C%)were
      30%, 37%, 32% and 33% in middle dose, high dose groups of 13cRA as well as their
      combination with IFN alpha-2b, respectively. 2 Comparing with the negative
      control, both 13cRA at different doses and its combination with IFNalpha-2b
      remarkably inhibited the tumor growth (P<0.05), while no statistic significance
      existed in different dose group of 13cRA. IFN-alpha 2b alone didn't demonstrate
      the tumor-inhibition effects (P>0.05). Middle dose of 13cRA and its combination
      with IFN-alpha-2b demonstrated relatively high tumor-inhibition effects (59.2%
      and 62.6% respectively), which were similar to the effects in positive control
      (69.4%). 3 There was no statistic difference of Ki-67 in each experimental group.
      4 Comparing with negative control group, all doses of 13cRA and their
      combinations with IFNalpha-2b remarkably increased the apoptosis (P<0.05),
      similar to the positive control group (P>0.05). However, IFNalpha-2b alone didn'
      t promote the apoptosis of tumor tissue (P=0.098). 5 Comparing with negative
      control group, IFNalpha-2b combined with each dose of 13cRA significantly
      decreased the levels of cycling D1 and procaspase-9, while increased the level of
      cleaved caspase-9 (P<0.05), which were similar to the positive control group
      (P>0.05). Nevertheless, 13cRA alone didn't demonstrate such effects. Conclusion:
      In the MCL animal model, IFNalpha-2b alone showed no effects, but combined with
      IFNalpha-2b, 13cRA displayed anti-tumor effects at different doses. The anti
      tumor mechanism of 13cRA combined with IFNalpha-2b was probably down-regulation
      of the cyclin D1 expression, inhibition of cell proliferation and induction of
      apoptosis by activating caspase-9.

PMID- 27719723
TI  - [Efficacy and survival analysis of DICE regimen for 97 patients with relapsed or
      refractory Non-Hodgkin's lymphoma].
AB  - Objective: To investigate the efficacy and survival of the DICE regimen
      (cisplatin, ifosfamide, etoposide, dexamethasone) for relapsed and refractory
      NHL. Methods: Clinical data of 97 relapsed and refractory NHL patients treated
      with DICE regimen in Peking University Cancer Hospital between Sep 1. 2008 and
      Dec 31. 2013 were retrospectively analyzed, and then we evaluate the efficacy and
      safety of DICE regimen. Results: 1 There were 64 males and 33 females with a
      median age of 49 years. The most common pathological type was DLBCL (73.20%).
      There were 35 B-NHL patients used rituximab combined with DICE. Finally, a total
      of 26 patients underwent autologous stem cell transplantation (auto-HSCT) after
      the salvage chemotherapy. 2 The overall response rate (ORR) was 47.42%, the
      complete response (CR) rate was 22.68%. The ORR of the relapsed/progressive group
      was higher than the refractory group [67.57% (25/37) vs 35.00% (21/60), chi2=
      9.736, P=0.002]. 3The median follow-up of these 97 patients was 15.0 months (1.5
      80.0 months). The expected median progression-free survival (PFS) and overall
      survival (OS) was 12.0 (95% CI 5.0-19.0) months, 26.0 (95% CI 6.0-45.9) months.
      4There was no difference between the auto-HSCT group and no auto-HSCT group in
      the median OS [41.0 (95%CI 8.9-73.1) vs 22.0 (95%CI 8.5-35.5) months, P=0.361].
      The patients who achieved CR and PR after DICE regimen had longer OS than those
      patients who in stable or progressive disease (56.0 vs 18.5 months, P <0.001).
      Patients who used DICE combined with rituximab had longer OS than patients who
      only used DICE regimen (51.5 vs 28.5 months, P=0.041). The multiple-factor
      analysis showed that the efficacy of DICE was an independent prognostic factor of
      OS [HR=4.24 (95%CI 2.12-8.50), P<0.001 ]. 5 The major adverse events included
      neutropenia (84.54% ) , thrombocytopenia (41.24% ), anemia (68.04%), and
      nausea/vomiting (65.98%), 14 patients (14.43%) had liver function abnormality, 1
      patient had acute renal function injury during the treatment period. There was no
      chemotherapy-related death occurred. Conclusion: The DICE regimen is effective in
      refractory and relapsed NHL, and DICE is safe and well-tolerated. The high
      response rate of DICE regimen may correlate with good prognosis. For the B-NHL
      patients who used DICE combined with rituximab had longer OS than those patients
      who used DICE regimen only.

PMID- 27719725
TI  - [The establishment and application of internal quality control system for real
      time quantitative PCR detection of BCR-ABL (P210) transcript levels].
AB  - Objective: To set internal quality control system of BCR-ABL (P210) transcript
      levels for real-time quantitative PCR (RQ-PCR). Methods: Using K562 cells and HL
      60 cells, we prepared high- and low-level BCR-ABL internal quality control
      substance. The BCR-ABL (P210) transcript levels of internal quality control
      substance have been determined for 184 times together with clinical samples from
      August 2013 to October 2015. The slope rate, intercept and correlation
      coefficient of standard curve were calculated according to different reagent lots
      (lots number 20130303, 20131212, 20140411 and 20150327 are called R1,R2,R3 and R4
      for short respectively), and the detection results of quality control substance
      were calculated according to different reagent lots and quality control substance
      lots (lots number 20130725, 20140611 are called Q1,Q2 for short respectively).
      Then the results were analyzed by Levey-Jennings quality control chart combined
      with Westgard multi-rules theory. Results: 1We analyzed the slope rate and
      intercept of standard curve. Fifty-three times of the R1 reagent detection, 80
      times of the R3 reagent detection and 14 times of the R4 reagent detection were
      all under control. For 37 times detection of R2 reagent, the slope rate was out
      of control for 6 times. It was lower than x-s for the 2-8 tests and upper the
      average for the 12-37 tests. The intercept was out of control for 9 times, upper
      the x+s for the 1-8 tests and lower the average for the 12-37 tests. 2 According
      to the detection results of quality control substance, for Q1 quality control
      substance, 49 tests by R1 reagent were under control, and 1 out of 23 tests by R2
      reagent was out of control. For Q2 quality control substance, 14 tests by R2
      reagent detection, 72 tests by R3 reagent detection and 14 tests by R4 reagent
      were all under control. Conclusion: The preparation of high- and low-level
      quality control substance using K562 and HL-60 cells was convenient and the
      detection results were reliable and stable. The application of quality control
      substance combined with slope rate and intercept in the internal quality control
      may contribute to quality assurance for quantitative detection of BCR-ABL (P210)
      transcript levels.

PMID- 27719724
TI  - [Effects of DNA methylation on ABO gene expression in leukemia].
AB  - Objective: To investigate the impact of promoter CpG island methylation on ABO
      mRNA expression in leukemia. Methods: 25 cases of leukemia and 20 cases of normal
      control were studied, and the leukemia cell lines K562,HL-60 and Jurkat were
      treated with different concentrations of decitabine. PCR-SSP was used to identify
      ABO genotype, RQ-PCR for ABO mRNA expression and bisulfite sequencing PCR for DNA
      methylation status. Results: 1 The methylation of ABO promoter in acute myeloid
      leukemia patients (10 cases) and acute lymphoblastic leukemia patients (10 cases)
      were 53.85% and 18.22% respectively, which were obviously higher than those in
      control (20 cases, 2.33%) and chronic myeloid leukemia patients (5 cases, 2.12%
      ). 2 ABO genotype of K562 was O1O1, which has changed little before and after
      decitabine treatment. ABO genotype of HL-60 and Jurkat could not been identify
      before treatment, but showed as O1A1 and A1O2 after treatment. 3ABO mRNA
      expression of K562 was 1 275.67 +/- 35.86, which was obviously higher than that
      in HL-60 (0.54 +/- 0.07, P<0.05) and Jurkat (0.82+/-0.16, P<0.05). 4The
      methylation of ABO promoter in K562, HL-60 and Jurkat were 0, 58.14%, and 96.74%.
      As concentration of decitabine increased, the methylation of ABO promoter were
      decreased and the expressions of ABO mRNA were increased in HL-60 and Jurkat,
      which had significant differences compared with that before treatment (P<0.05).
      Conclusion: The methylation of ABO promoter shows a negative correlation with ABO
      mRNA expression. DNA methylation was an important aspect of ABO antigens decrease
      in acute leukemia.

PMID- 27719727
TI  - [Analysis of HBV, HCV and EBV infections in diffuse large B cell lymphoma].

PMID- 27719726
TI  - [The clinical feature and outcomes of severe aplastic anemia patients suffered
      from bacteremia following antithymocyte globulin].
AB  - Objective: To assess the clinical feature and outcomes of severe aplastic anemia
      (SAA) patients suffered from bacteremia following antithymocyte globulin (ATG).
      Methods: A total of 264 cases hospitalized in our hospital between Jan 2000 and
      July 2011 were enrolled into this study. We evaluated the associated pathogens of
      bacteremia, analyzed the risk factors by Logistic regression and estimated the
      overall survival (OS) by Kaplan-Meier method for the cohort of patients. Results:
      Bloodstream infections occurred in 49 patients, with a median age of 20 (4-62)
      years, including 38 cases with very SAA (VSAA) and 11 SAA patients. The median
      time of bacteremia was 13 (2-233) days following ATG administration. The most
      common microbiologically were Enterobacteriaceae (28.4% ), Pseudomonas aeruginosa
      (20.9% ) and Klebsiella pneumonia (14.9% ). Almost half (46.9% ) of these
      bacteria were resistant to most or all available antibacterial classes.
      Univariate and multivariate analyses demonstrated that VSAA, infections during
      previous week before ATG treatment were risk factors for bacteremia. The 3 and 6
      months response rates (10.6% and 17.0% ) were poor in the patients with
      bloodstream infections, which were significantly lower than those patients
      without infections (35.6% and 55.6%, respectively, both P<0.001). The estimated 5
      year OS were 36.4% (95%CI 21.3% to 51.5%) and 74.5% (95%CI 68.4% to 80.7%) in the
      two groups, respectively (P<0.001). Conclusions: 1VSAA has higher risk of
      bacteremia than SAA; 2Infections during previous week before ATG administration
      was a risk factor for bacteremia; 3 The outcomes of SAA or VSAA patients suffered
      from bacteremia following ATG was poor.

PMID- 27719728
TI  - [A case report of T-cell prolymphocytic leukemia complicated with Budd-Chiari
      syndrome and literature review].

PMID- 27719729
TI  - [Diagnostic and treatment cost of invasive fungal infections in patients with
      hematologic malignancies during hospitalization].

PMID- 27719730
TI  - [Classical Hodgkin lymphoma in north Anhui province of China: a clinic
      pathological analysis of 56 cases].

PMID- 27719731
TI  - [Association of IKZF1 gene polymorphism with acute lymphoblastic leukemia in
      Chinese children].

PMID- 27719732
TI  - [Research progress on PD-1 inhibitors in lymphoma therapy].

PMID- 27719733
TI  - Does on-site chaplaincy enhance the health and well being of fly-in, fly-out
      (FIFO) personnel?
AB  - Issue addressed The fly-in, fly-out (FIFO) work style has been linked to mental
      health and interpersonal issues and a need for strategies that maintain a healthy
      workforce. This study investigated whether 24/7 on-site chaplains deliver a
      service that promotes the health and well being of FIFO personnel. Methods A
      phenomenological approach was used to explore the perceptions of FIFO personnel
      working in different roles and organisational sections on a remote mine site in
      Western Australia. Multi-pronged strategies recruited 29 participants who
      represented management, supervisors, workers and support staff. Participants took
      part in semistructured interviews conducted either one-on-one or in pairs.
      Results Chaplains were described as making a valuable contribution to the
      physical and mental health of FIFO personnel. Specific aspects of the service
      such as active outreach, effective trust building and the on-site availability
      were identified as central to the service being accessed and overcoming barriers
      embedded in mining culture and masculinity. Conclusions On-site chaplaincy
      appears to be effective in promoting the physical and mental health of FIFO
      personnel working at a remote mine site. So what? This promising model of active
      on-site outreach offered by chaplains is set apart from existing FIFO support
      structures. We recommend further exploration of its potential to become part of
      an integrated health-support system in the mining sector and other industries.

PMID- 27719734
TI  - Reach, engagement, and effectiveness: a systematic review of evaluation
      methodologies used in health promotion via social networking sites.
AB  - Issue addressed Social networking sites (SNS) are increasingly popular platforms
      for health promotion. Advancements in SNS health promotion require quality
      evidence; however, interventions are often not formally evaluated. This study
      aims to describe evaluation practices used in SNS health promotion. Methods A
      systematic review was undertaken of Medline, PsycINFO, Scopus, EMBASE, CINAHL
      Plus, Communication and Mass Media Complete, and Cochrane Library databases.
      Articles published between 2006 and 2013 describing any health promotion
      intervention delivered using SNS were included. Results Forty-seven studies were
      included. There were two main evaluation approaches: closed designs (n=23), which
      used traditional research designs and formal recruitment procedures; and open
      designs (n=19), which evaluated the intervention in a real-world setting,
      allowing unknown SNS users to interact with the content without enrolling in
      research. Closed designs were unable to assess reach and engagement beyond their
      research sample. Open designs often relied on weaker study designs with no use of
      objective outcome measures and yielded low response rates. Conclusions Barriers
      to evaluation included low participation rates, high attrition, unknown
      representativeness and lack of comparison groups. Acceptability was typically
      assessed among those engaged with the intervention, with limited population data
      available to accurately assess intervention reach. Few studies were able to
      assess uptake of the intervention in a real-life setting while simultaneously
      assessing effectiveness of interventions with research rigour. So what? Through
      use of quasi-experimental or well designed before-after evaluations, in
      combination with detailed engagement metrics, it is possible to balance
      assessment of effectiveness and reach to evaluate SNS health promotion.

PMID- 27719736
TI  - Regression of vascular calcification in a parathyroidectomized patient on
      dialysis with untreated hypocalcemia over 12-year follow-up?.
AB  - Although some experimental targets involved in calcium deposition are emerging,
      no intervention has been described to reliably reverse vascular calcification
      (VC). We report a case of severe VC regression in a parathyroidectomized patient
      on hemodialysis over 12-year follow-up, highlighting the use of calcium-free
      phosphate binders and a 2.5 mEq/L calcium dialysate for reducing calcium loading,
      despite persistent asymptomatic hypocalcemia occurrences. This case suggests that
      phosphate-binder choice and calcium dialysate concentration could be influenced
      by other components of CKD-MBD besides biochemical parameters, such as the
      presence of VC, so concluding that asymptomatic hypocalcemia may not be as
      harmful as once supposed, and conferring greater prognostic weight to the
      presence of VC than to calcium levels.?.

PMID- 27719735
TI  - Applying systems theory to the evaluation of a whole school approach to violence
      prevention.
AB  - Issue addressed Our Watch led a complex 12-month evaluation of a whole school
      approach to Respectful Relationships Education (RRE) implemented in 19 schools.
      RRE is an emerging field aimed at preventing gender-based violence. This paper
      will illustrate how from an implementation science perspective, the evaluation
      was a critical element in the change process at both a school and policy level.
      Methods Using several conceptual approaches from systems science, the evaluation
      sought to examine how the multiple systems layers - student, teacher, school,
      community and government - interacted and influenced each other. A distinguishing
      feature of the evaluation included 'feedback loops'; that is, evaluation data was
      provided to participants as it became available. Evaluation tools included a
      combination of standardised surveys (with pre- and post-intervention data
      provided to schools via individualised reports), reflection tools, regular
      reflection interviews and summative focus groups. Results Data was shared during
      implementation with project staff, department staff and schools to support
      continuous improvement at these multiple systems levels. In complex settings,
      implementation can vary according to context; and the impact of evaluation
      processes, tools and findings differed across the schools. Interviews and focus
      groups conducted at the end of the project illustrated which of these methods
      were instrumental in motivating change and engaging stakeholders at both a school
      and departmental level and why. Conclusion The evaluation methods were a critical
      component of the pilot's approach, helping to shape implementation through data
      feedback loops and reflective practice for ongoing, responsive and continuous
      improvement. Future health promotion research on complex interventions needs to
      examine how the evaluation itself is influencing implementation. So what? The
      pilot has demonstrated that the evaluation, including feedback loops to inform
      project activity, were an asset to implementation. This has implications for
      other health promotion activities, where evaluation tools could be utilised to
      enhance, rather than simply measure, an intervention. The findings are relevant
      to a range of health promotion research activities because they demonstrate the
      importance of meta-evaluation techniques that seek to understand how the
      evaluation itself was influencing implementation and outcomes.

PMID- 27719737
TI  - The other side of vitamin D therapy: ?a case series of acute kidney injury due to
      malpractice-related vitamin D intoxication?.
AB  - BACKGROUND: Vitamin D deficiency is highly prevalent in Indian Kashmir. Many
      people get injectable vitamin D (600,000 IU/injection). At times, the dose
      prescribed is far above the permissible limit. We report 62 patients with
      malpractice-related vitamin D intoxication, presenting with hypercalcemia and
      acute kidney injury (AKI). METHODS: The diagnosis was made on basis of (1)
      history of multiple intramuscular vitamin D injections (2) toxic serum levels of
      25-OH vitamin D and (3) exclusion of common causes of hypercalcemia (malignancy
      and hyperparathyroidism). Their presentation was either de novo AKI in 51 (group
      1) or acute on top of chronic kidney disease in 11 (group 2). RESULTS: The mean
      age was 60 +/- 14 vs. 62 +/- 13 years, approximate number of vitamin D injections
      received ranged from 4 to 28 (2.4 - 16.8 million units) vs. 3 to 24 (1.8 - 14.4
      million units), mean creatinine at presentation was 3.2 +/- 0.9 vs. 4.5 +/- 1.1
      mg/dL, which decreased to 1.2 +/- 0.2 vs. 3.3 +/- 1.0 mg/dL, mean serum calcium
      on admission was 13.7 +/- 1.4 vs. 13.6 +/- 2.0 mg/dL which decreased to 10.7 +/-
      1.2 vs. 11.0 +/- 1.0 mg/dL on follow-up of 7.2 +/- 0.6 months, mean vitamin D
      level was 313.3 +/- 54.8 (range 235 - 375) vs. 303.7 +/- 48.4 (range 210 - 375)
      nmol/L and mean PTH was 18.1 +/- 9.6 (range 6.2 - 32) vs. 52.3 +/- 12.6 (range 28
      - 88) pg/mL in group 1 vs. group 2, respectively. The clinical presentation was
      weakness, constipation, abdominal pain, nausea, vomiting, anorexia, altered
      sensorium, and oliguria. The treatment received was intravenous fluids (normal
      saline) in all in group 1 and in 8/11 in group 2, short course of steroids
      (prednisolone) in 44, and bisphosphonate in 6. CONCLUSION: This is the largest
      case series of AKI secondary to vitamin D toxicity ever reported.?.

PMID- 27719738
TI  - Bendamustine-induced nephrogenic diabetes insipidus?.
AB  - A 59-year-old man presented with polyuria and polydipsia immediately following
      his sixth cycle of rituximab and bendamustine for chronic lymphocytic leukemia.
      He initially compensated by increasing his oral fluid intake at home, but later
      developed septic shock and was admitted with orders to be kept nil per os (NPO).
      This prompted an episode of acute hypernatremia during which he exhibited
      continued polyuria with inappropriately dilute urine. Desmopressin challenge
      yielded no response in the urine osmolality, indicating a nephrogenic source of
      his diabetes insipidus (DI). He had no known exposure to other causative agents
      and had demonstrated a robust response to chemotherapy. The patient became
      eunatremic once oral intake was resumed and his infection was treated. Two months
      after presentation, he remained symptomatic. A trial with hydrochlorothiazide
      resulted in a significant increase in urine osmolality and subsequent decrease in
      urine output. To our knowledge, this is the first case of nephrogenic diabetes
      insipidus after rituximab and bendamustine exposure. We propose that
      bendamustine, similar to the alkylating agent ifosfamide, is toxic to the
      glomerulus and proximal tubule cells and is the most likely cause of the
      patient's nephrogenic DI.?.

PMID- 27719739
TI  - Early recognition of gonadal dysgenesis in congenital nephrotic syndrome?.
AB  - Mutation of the Wilms tumor suppressor gene (WT1) has been recognized as one of
      the etiologies of steroid-resistant nephrotic syndrome (SRNS). The mutation is
      also responsible for gonadal dysgenesis in 46,XY individuals. Early recognition
      of the presence of Y chromosome is of particular importance because of the high
      risk of gonadal tumor. We present here three cases of steroid-resistant nephrotic
      syndrome with WT1 mutation and 46,XY karyotype. Patient 1 and 2 have intron
      splice site (IVS9+5G A) mutation. Patient 3 has c.1301GA (p. R434H) mutation. All
      cases had normal female external genitalia at birth and eluded the diagnosis of
      gonadal dysgenesis until later in life. We suggest that chromosomal analysis
      should be promptly performed in female patients with early-onset steroid
      resistant nephrotic syndrome.?.

PMID- 27719740
TI  - Berberine promotes antiproliferative effects of epirubicin in T24 bladder cancer
      cells by enhancing apoptosis and cell cycle arrest?.
AB  - OBJECTIVE: The present study was aimed to observe the effect of berberine (Ber)
      on epirubicin (EPI)-induced growth inhibition, apoptosis, and cell cycle arrest
      in T24 bladder cancer cells. METHODS: The cancer cells were exposed to EPI, with
      or without different concentrations of Ber. The viability of the cancer cells was
      measured by cell counting Kit-8, the apoptosis was determined by Hoechst 33258
      staining and the expression of cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax,
      and P53 proteins were detected by Western blot assay. In addition, cell cycle
      arrest and the production of reactive oxygen species (ROS) were also measured.
      RESULTS: We found that Ber enhanced the inhibitory effect of EPI on the viability
      of T24 cells and promoted EPI-induced cell cycle arrest at G0/G1 and apoptosis in
      T24 cells. EPI increased the expression of cleaved caspase-3, cleaved caspase-9,
      Bax, P53, and P21 proteins, all of which were enhanced by treatment with Ber. In
      contrast, Ber exposure further decreased the expression of Bcl-2 in EPI-treated
      T24 cells. Furthermore, we also demonstrated that Ber significantly increased ROS
      production in EPI-treated T24 cells. CONCLUSIONS: These data indicate that Ber
      enhances the antiproliferative effects of EPI in bladder cancer cells by
      promoting apoptosis and cell cycle arrest.?.

PMID- 27719741
TI  - Evaluation of the safety, pharmacokinetics, pharmacodynamics, and drug-drug
      interaction potential of a selective Lp-PLA2 inhibitor (GSK2647544) in healthy
      volunteers?.
AB  - OBJECTIVE: To evaluate in healthy volunteers the safety, pharmacokinetics (PK),
      pharmacodynamics (PD), and drug-drug interaction (DDI) potential of GSK2647544,
      (a selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor).
      METHODS: Study 1 was a single-blind, randomized, placebo-controlled, crossover
      study with healthy male volunteers randomized to receive single escalating oral
      doses (0.5 - 750 mg) of GSK2647544. Study 2 was a single-blind, randomized,
      placebo-controlled study with healthy volunteers randomized to receive repeat
      doses (80 mg) of GSK2647544. The drug-drug interaction of GSK2647544 with
      simvastatin was also evaluated in study 2. RESULTS: Across both studies
      GSK2647544 doses were generally well tolerated with no GSK2647544-related
      clinically significant findings. GSK2647544 was readily absorbed and its plasma
      concentration declined bi-exponentially with a terminal half-life ranging from 8
      to 16 hours. Plasma exposure of GSK2647544 increased approximately dose
      proportionally. There was GSK2647544 dose-dependent inhibition of plasma Lp-PLA2
      activity, with a trough inhibition (12 hours after dose) of 85.6% after 7-day
      twice daily dosing. The administration of simvastatin concomitantly with
      GSK2647544 increased the overall exposure (area under the plasma concentration
      time curve and maximum plasma concentration) of simvastatin and simvastatin acid
      by 3.6- to 4.3-fold and 1.5- to 3.1-fold, respectively. CONCLUSIONS: GSK2647544
      was generally well tolerated and had a reasonable PK-PD profile. The clinically
      significant drug-drug interaction led to an early termination of study 2.?.

PMID- 27719742
TI  - Blood lipid abnormality changes the rate of alveolar-capillary uptake of
      sevoflurane: a prospective, non-interventional, clinical study?.
AB  - OBJECTIVE: This research studied the influence of different blood lipid
      components on the rate of alveolar-capillary uptake of sevoflurane.
      <u>Method:</u> 104 patients aged 20 - 50 years undergoing elective operations
      under general anesthesia were mechanically ventilated through endotracheal
      intubation after intravenous injections of midazolam, vecuronium, fentanyl, and
      etomidate. They inhaled 2% sevoflurane at an oxygen flow of 2 L/min, then the
      inspired concentrations (F<sub>I</sub>) and expired concentrations (F<sub>A</sub>
      of sevoflurane were recorded at 1, 3, 5, 7, 10, 15, 20, and 30 minutes. These
      cases were divided into a normal group and an abnormal group according to the
      lipid levels. Then, based on the lipid criteria, those cases with abnormal lipid
      levels were classified into a high-triglyceride (TG) and total-cholesterol (TC)
      group (group TG+TC) and a group with decreased high-density lipoprotein
      cholesterol (group HDL-C).The values of F<sub>A</sub>/F<sub>I</sub> and the times
      required to reach the titration value F<sub>A</sub>/F<sub>I</sub> = 0.8 were
      calculated were calculated for each group. RESULTS: Compared with the normal
      group, F<sub>A</sub>/F<sub>I</sub> decreased within 7 - 10 minutes (p < 0.05) and
      the time taken to reach the titration value was prolonged in the abnormal group
      (p < 0.05). The value of F<sub>A</sub>/F<sub>I</sub> decreased during 7 - 10
      minutes (p < 0.05) and the time taken to reach the titration value was longer (p
      < 0.05) in the group TG+TC. CONCLUSIONS: The increased value of blood/gas
      partition coefficients (B/G) was caused by the increase in the concentrations of
      TG and TC in blood lipids.?.

PMID- 27719743
TI  - Effect of food on the oral bioavailability of the angiotensin receptor -
      neprilysin inhibitor sacubitril/valsartan (LCZ696) in healthy subjects?.
AB  - OBJECTIVE: Sacubitril/valsartan (LCZ696) provides a novel therapeutic approach of
      neurohormonal modulation in heart failure via simultaneous inhibition of
      neprilysin and blockade of the angiotensin II type-1 receptor. This study was
      conducted to evaluate the effect of food on the oral bioavailability of LCZ696
      analytes. MATERIALS AND METHODS: This was an open-label, randomized, 3-period
      crossover study in healthy subjects. Eligible subjects (N = 36) were randomized
      to 6 treatment sequences, each comprising 3 treatment periods during which
      subjects received a single oral dose of 400 mg LCZ696 under fasting condition and
      following a low- and high-fat meal. RESULTS: Following administration of LCZ696
      after low- and high-fat meals, the mean C<sub>max</sub> of sacubitril and
      sacubitrilat (the active neprilysin inhibitor) decreased by 42 - 54% and 19 -
      28%, respectively, while the t<sub>max</sub> values increased. However, systemic
      exposure (AUC<sub>inf</sub> and AUC<sub>last</sub>) of sacubitril was slightly
      decreased (by 16% with low-fat meal) and that of sacubitrilat was unchanged in
      the presence of food. For valsartan, the C<sub>max</sub> decreased by ~ 40% when
      LCZ696 was administered after low- and high-fat meals. The systemic exposure of
      valsartan decreased by ~ 33% with a low-fat meal; however, it was unchanged with
      a high-fat meal. LCZ696 was generally safe and well tolerated in healthy subjects
      when administered under fasting or fed condition. CONCLUSION: Overall,
      administration of LCZ696 with meals decreased the rate and extent of absorption
      of sacubitril with little impact on the systemic exposure to sacubitrilat, its
      active metabolite. The systemic exposure to valsartan was decreased in the
      presence of food.?.

PMID- 27719744
TI  - Tolerability and safety of Octagam(r) (IVIG): a post-authorization safety
      analysis of four non-interventional phase IV trials?.
AB  - OBJECTIVE: To evaluate the tolerability and safety of Octagam<sup>(r)</sup> 5%
      and 10% across all indications, ages, and treatment regimens, using data from
      four non-interventional post-authorization safety studies (PASS); this analysis
      was performed following changes in the preparation of raw material used to
      manufacture Octagam. METHODS: All four studies included in- and out-patients
      prescribed Octagam for treatment of their medical condition. Physicians used case
      report forms to document baseline demographics, Octagam treatment details, and
      data on the efficacy of Octagam, and recorded all adverse drug reactions (ADRs)
      and other safety data. RESULTS: Altogether 21,780 infusions of Octagam in 2,397
      patients were included in our analysis. The most frequent indication for Octagam
      was secondary immunodeficiencies (SID; n = 1,368, 11,348 infusions), followed by
      primary immunodeficiencies (PID; n = 363; 3,923 infusions). During the individual
      patient observation, 83% of SID and 67% of PID patients were free of any
      infection. In up to 85% of all investigator assessments, Octagam was rated to
      have a favorable effect. In autoimmune diseases, investigators assessed Octagam
      as being beneficial in 70% (immune thrombocytopenia) up to 100% (Guillain-Barre
      syndrome), depending on the indication. The majority of patients (92%) tolerated
      Octagam treatment without any ADR. The overall incidence of reported ADRs was
      1.0% for all infusions. The majority of ADRs were considered non-serious (93%)
      and mild or moderate (87%) in severity. No unexpected ADR signal was detected.
      CONCLUSIONS: This analysis demonstrates that the changes in the preparation of
      raw material used to manufacture Octagam did not affect the safety profile of
      Octagam<sup>(r)</sup> 5% and 10%.? *At the time of study realization.

PMID- 27719746
TI  - Brain metastasis from gastrointestinal clear cell sarcoma.
AB  - Clear cell sarcoma (CCS) of the gastrointestinal tract presents a diagnostic
      challenge to the pathologist due to its morphological and immunohistochemical
      similarity to melanoma. It usually metastasizes to regional lymph nodes, liver,
      and lungs. Herein, we report the first known metastasis of a gastrointestinal CCS
      to the central nervous system. Cytogenetic testing showed the t(12,22)
      translocation corresponding to the presence of the EWS/ATF1 hybrid consistent
      with CCS. The literature that compares melanoma to CCS is reviewed in the context
      of this rare presentation to differentiate between the two diseases.?.

PMID- 27719745
TI  - Pathological background of subcortical hyperintensities on diffusion-weighted
      images in a case of neuronal intranuclear inclusion disease.
AB  - AIMS: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative
      disorder with eosinophilic intranuclear inclusion bodies. The variable symptoms
      of NIID increase the difficulty in an antemortem diagnosis. NIID shows
      leukoencephalopathy on brain magnetic resonance imaging MRI, but the significance
      of the radiological findings have not been clarified. METHODS: We examined an
      autopsied case of NIID with subcortical linear hyperintensities on diffusion
      weighted imaging (DWI) and leukoencephalopathy on fluid attenuation inversion
      recovery (FLAIR) imaging. Semiquantitative analysis was performed by merging
      coronal sections of DWI and identical hematoxylin-eosin (H & E) stained brain
      specimens. The severity of spongiotic changes, the common pathological findings
      of NIID, were quantified and compared with MRI lesions classified by DWI signals.
      RESULTS: The white matter showed diffuse myelin pallor, and multiple focal
      spongiotic changes were present in the subcortical white matter proximal to the U
      fibers. Spongiotic changes were restricted in the lesions with subcortical linear
      DWI high signals. CONCLUSION: Subcortical DWI high signals in NIID strongly
      correlate with pathological spongiotic changes of NIID. Subcortical spongiotic
      changes may be a characteristic finding of NIID.?.

PMID- 27719747
TI  - Mitochondrial proteomics reveal potential targets involved in mitochondrial
      abnormalities of desminopathy.
AB  - AIMS: To investigate the underlying mechanisms of how the defects of desmin cause
      mitochondrial abnormalities in desminopathy. MATERIAL AND METHODS: Primary
      myoblasts were isolated from muscle biopsy of a desminopathy patient with
      mitochondrial abnormalities. Two-dimensional gel electrophoresis analyses of
      mitochondrial proteins were performed in mitochondria isolated from myoblasts.
      Immunostaining, immunoblot, and mitochondrial function tests were carried out to
      confirm the proteomic results. RESULTS: 42 proteins were found with significant
      expression differences in the mitochondrial proteomics. Several proteins
      associated with regulation of the mitochondrial permeability transition pore
      (MPTP) complex were identified in functional cluster analysis. The patterns of
      protein expression were also confirmed by strong immunoreactivity, increased MPTP
      opening and elevated level of oxidative stress. CONCLUSIONS: The study provides
      an overall perspective of the mitochondrial proteome plasticity in a case of
      desminopathy with mitochondrial abnormalities. The expression patterns of protein
      associated with MPTP indicate that desmin might affect MPTP complex as potential
      targets involved in mitochondrial dysfunction in desminopathy. However, the
      precise underlying mechanism remains to be elucidated.?.

PMID- 27719748
TI  - Astrocytoma with extensive infiltration of Virchow-Robin spaces.

PMID- 27719749
TI  - A rare case of primary intracerebral Hodgkin lymphoma.

PMID- 27719750
TI  - A norovirus intervariant GII.4 recombinant in Victoria, Australia, June 2016: the
      next epidemic variant?
AB  - A norovirus recombinant GII.P4_NewOrleans_2009/GII.4_Sydney_2012 was first
      detected in Victoria, Australia, in August 2015 at low frequency, and then re
      emerged in June 2016, having undergone genetic changes. Analysis of 14 years'
      surveillance data from Victoria suggests a typical delay of two to seven months
      between first detection of a new variant and occurrence of a subsequent epidemic
      linked to that variant. We consider that the current recombinant strain has the
      potential to become a pandemic variant.

PMID- 27719751
TI  - Increase in ECHOvirus 6 infections associated with neurological symptoms in the
      Netherlands, June to August 2016.
AB  - The Dutch virus-typing network VIRO-TypeNed reported an increase in ECHOvirus 6
      (E-6) infections with neurological symptoms in the Netherlands between June and
      August 2016. Of the 31 cases detected from January through August 2016, 15
      presented with neurological symptoms. Ten of 15 neurological cases were detected
      in the same province and the identified viruses were genetically related. This
      report is to alert medical and public health professionals of the circulation of
      E-6 associated with neurological symptoms.

PMID- 27719753
TI  - Letter to the editor: The first tick-borne encephalitis case in the Netherlands:
      reflections and a note of caution.

PMID- 27719754
TI  - Expert committee declares WHO Region of the Americas measles-free.

PMID- 27719752
TI  - VIRO-TypeNed, systematic molecular surveillance of enteroviruses in the
      Netherlands between 2010 and 2014.
AB  - VIRO-TypeNed is a collaborative molecular surveillance platform facilitated
      through a web-based database. Genetic data in combination with epidemiological,
      clinical and patient data are shared between clinical and public health
      laboratories, as part of the surveillance underpinning poliovirus eradication. We
      analysed the combination of data submitted from 2010 to 2014 to understand
      circulation patterns of non-polio enteroviruses (NPEV) of public health
      relevance. Two epidemiological patterns were observed based on VIRO-TypeNed data
      and classical surveillance data dating back to 1996: (i) endemic cyclic,
      characterised by predictable upsurges/outbreaks every two to four years, and (ii)
      epidemic, where rare virus types caused upsurges/outbreaks. Genetic analysis
      suggests continuous temporal displacement of virus lineages due to the
      accumulation of (silent) genetic changes. Non-synonymous changes in the antigenic
      B/C loop suggest antigenic diversification, which may affect population
      susceptibility. Infections were frequently detected at an age under three months
      and at an older, parenting age (25-49 years) pointing to a distinct role of
      immunity in the circulation patterns. Upsurges were detected in the summer and
      winter which can promote increased transmissibility underlying new (cyclic)
      upsurges and requires close monitoring. The combination of data provide a better
      understanding of NPEV circulation required to control and curtail upsurges and
      outbreaks.

PMID- 27719755
TI  - French Aedes albopictus are able to transmit yellow fever virus.
AB  - We assessed the ability of a French population of Aedes albopictus to transmit
      yellow fever virus (YFV). Batches of 30 to 40 female mosquitoes were analysed at
      7, 14 and 21 days post-exposure (dpe). Bodies, heads and saliva were screened for
      YFV. Infectious viral particles were detected in bodies and heads at 7, 14 and 21
      dpe whereas the virus was found in saliva only from 14 dpe. Our results showed
      that Ae. albopictus can potentially transmit YFV.

PMID- 27719756
TI  - 'European Antibiotics Awareness Day' wins 'European Health Award 2016' accolade.

PMID- 27719757
TI  - Authors' correction for Euro Surveill. 2016;21(38).

PMID- 27719758
TI  - Author's reply: The first tick-borne encephalitis case in the Netherlands:
      reflections and a note of caution.

PMID- 27719759
TI  - Cortical flow aligns actin filaments to form a furrow.
AB  - Cytokinesis in eukaryotic cells is often accompanied by actomyosin cortical flow.
      Over 30 years ago, Borisy and White proposed that cortical flow converging upon
      the cell equator compresses the actomyosin network to mechanically align actin
      filaments. However, actin filaments also align via search-and-capture, and to
      what extent compression by flow or active alignment drive furrow formation
      remains unclear. Here, we quantify the dynamical organization of actin filaments
      at the onset of ring assembly in the C. elegans zygote, and provide a framework
      for determining emergent actomyosin material parameters by the use of active
      nematic gel theory. We characterize flow-alignment coupling, and verify at a
      quantitative level that compression by flow drives ring formation. Finally, we
      find that active alignment enhances but is not required for ring formation. Our
      work characterizes the physical mechanisms of actomyosin ring formation and
      highlights the role of flow as a central organizer of actomyosin network
      architecture.

PMID- 27719762
TI  - Local, Regional, and Spinal Anesthesia in Ruminants.
AB  - Local, regional, and spinal anesthesias are safe, effective, often more desirable
      procedures for ruminants than general anesthesia. Many procedures can be
      performed safely and humanely in ruminants using a combination of physical
      restraint, mild sedation, and local, regional, or spinal anesthesia. This article
      focuses on the use of local anesthetics for providing anesthesia for dehorning,
      procedures of the nose and eye, laparotomy, reproductive procedures, teat repair,
      and procedures on the distal limb. Local, regional, and spinal anesthesia
      techniques are safe effective methods for providing anesthesia for common
      surgical procedures and analgesia for painful conditions in cattle and small
      ruminants.

PMID- 27719761
TI  - Asymmetric effects of activating and inactivating cortical interneurons.
AB  - Bidirectional manipulations - activation and inactivation - are widely used to
      identify the functions supported by specific cortical interneuron types. Implicit
      in much of this work is the notion that tonic activation and inactivation will
      both produce valid, internally consistent insights into interneurons'
      computational roles. Here, using single-unit recordings in auditory cortex of
      awake mice, we show that this may not generally hold true. Optogenetically
      manipulating somatostatin-positive (Sst+) or parvalbumin-positive (Pvalb+)
      interneurons while recording tone-responses showed that Sst+ inactivation
      increased response gain, while Pvalb+ inactivation weakened tuning and decreased
      information transfer, implying that these neurons support delineable
      computational functions. But activating Sst+ and Pvalb+ interneurons revealed no
      such differences. We used a simple network model to understand this asymmetry,
      and showed how relatively small changes in key parameters, such as spontaneous
      activity or strength of the light manipulation, determined whether activation and
      inactivation would produce consistent or paradoxical conclusions regarding
      interneurons' computational functions.

PMID- 27719763
TI  - Surgery of the Sinuses and Eyes.
AB  - Conditions of the head requiring surgery in cattle are not uncommon when
      considering the incidence of conditions such as ocular squamous cell carcinoma
      and requests for surgical dehorning. Surgery involving the eyes in cattle is
      relatively common, whereas surgery of the paranasal sinuses is less common.
      Generally speaking, however, surgery for conditions of the head tend to have a
      more favorable prognosis when there is early intervention.

PMID- 27719764
TI  - Surgery of the Forestomach.
AB  - Indications for rumen surgery include rumen tympany (bloat), toxic plant
      ingestion, to provide enteral nutrition, to perform elective cannula placement,
      and to access other forestomach compartments (reticulum/omasum). The rumen is a
      highly contaminated viscus and special care should be taken to avoid peritoneal
      contamination from rumen contents. Diseases causing forestomach dysfunction and
      surgical procedures on the forestomach compartments are discussed here.

PMID- 27719760
TI  - BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem
      and progenitor cell development.
AB  - Notch signaling plays a crucial role in controling the proliferation and
      differentiation of stem and progenitor cells during embryogenesis or
      organogenesis, but its regulation is incompletely understood. BLOS2, encoded by
      the Bloc1s2 gene, is a shared subunit of two lysosomal trafficking complexes,
      biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1-related
      complex (BORC). Bloc1s2-/- mice were embryonic lethal and exhibited defects in
      cortical development and hematopoiesis. Loss of BLOS2 resulted in elevated Notch
      signaling, which consequently increased the proliferation of neural progenitor
      cells and inhibited neuronal differentiation in cortices. Likewise, ablation of
      bloc1s2 in zebrafish or mice led to increased hematopoietic stem and progenitor
      cell production in the aorta-gonad-mesonephros region. BLOS2 physically
      interacted with Notch1 in endo-lysosomal trafficking of Notch1. Our findings
      suggest that BLOS2 is a novel negative player in regulating Notch signaling
      through lysosomal trafficking to control multiple stem and progenitor cell
      homeostasis in vertebrates.

PMID- 27719765
TI  - Urolithiasis.
AB  - Urolithiasis is the most common urinary problem in male ruminants, and one of the
      most common emergencies in male goats and sheep. This disease has substantial
      welfare implications because it causes severe pain and it has a high fatality
      rate. The expense associated with veterinary care and loss of affected animals
      has a strong economic impact on pet owners and farmers.

PMID- 27719766
TI  - Surgical Procedures of the Genital Organs of Bulls.
AB  - Reproductive surgical techniques are considered by practitioners of
      theriogenology to be the best method to manage infertility-causing conditions or
      diseases of the bull. Injury or diseases of the reproductive tract may cause
      abnormalities that may result in substantial losses to the producers of beef and
      dairy cattle. The most cost-effective method of dealing with reproductive
      conditions or diseases of the bull is culling and replacement. Some injuries,
      diseases, or conditions are amenable to surgical management. Surgical management
      may preserve the genetic potential of the bull and economic productivity. The
      surgical procedures described are commonly used methods to restore fertility in
      bulls.

PMID- 27719767
TI  - Surgical Procedures of the Genital Organs of Cows.
AB  - Reproductive surgical techniques are considered by practitioners/clinicians of
      theriogenology to be the most beneficial reproductive management that can be
      performed to treat conditions of cows that may affect fertility. Conditions
      affecting the reproductive tract can cause pathologic changes that may result in
      substantial economic and genetic losses to beef and dairy producers. Some
      injuries and diseases are amenable to surgical treatment. Surgical restoration of
      fertility preserves genetic potential and economic productivity. The surgical
      procedures described in this article are some of the most commonly used to
      restore fertility in cows with injury or diseases affecting their reproductive
      tracts.

PMID- 27719768
TI  - Surgery of the Distal Limb.
AB  - Diseases of the bovine digit remain the major cause of painful lameness in cattle
      and commonly constitute a diagnostic and therapeutic challenge for clinicians.
      Prompt surgical wound revision is critical in acute injuries. Deep infections may
      be treated with debridement, resection of tendons, synovioscopy, joint lavage,
      arthrotomy and facilitated joint ankylosis. Postoperative care is more involved,
      lameness persists longer, and cost of treatment is higher after salvage
      techniques than after amputation of the digit. Luxations and fractures of the
      digits often are amenable to conservative treatment but may be treated surgically
      if indicated.

PMID- 27719769
TI  - Surgical Management of the Teat and the Udder.
AB  - Lacerations of the teat should be treated as emergency. First-intention repair
      should be attempted under sedation in lateral or dorsal recumbency. Surgeons
      should pay attention to the atraumatic manipulation of the tissue and the
      anatomic reconstruction using small-diameter absorbable suture material. Hand
      milking should be prohibited for 10 days postoperatively after laceration repair;
      prognosis is overall good. Ultrasound evaluation of the teat allows excellent
      understanding of the internal lesions and should be performed before planning any
      elective surgery. Milk outflow impairment originating from the rosette of
      Furstenberg or the streak canal is best treated using minimally invasive surgery
      (theloscopy).

PMID- 27719770
TI  - Ruminant Surgery.

PMID- 27719772
TI  - Correction to "Becoming Baby-Friendly and Transforming Maternity Care in a Safety
      Net Hospital on the Texas-Mexico Border".

PMID- 27719771
TI  - Applying Evidence to Health Care With Archie Cochrane's Legacy.

PMID- 27719773
TI  - Changing Challenges and Evolving Opportunities in Nursing Education.
AB  - With more people having access to health care in the United States as a result of
      the Affordable Care Act, there is a greater need for nurses now than ever before.
      Generalist nurses will need to be educated, not just to care for people in
      hospitals, but also to promote health and help manage chronic conditions in a
      wide variety of health care settings. More advanced-practice nurses will be
      needed to provide primary care. Although the need for nurses educated at both the
      undergraduate and graduate levels in emerging health care systems is increasing,
      the number of nursing educators is decreasing. Nursing educators in the future
      will need to be nimble in addressing emerging health care needs while ensuring
      succession planning.

PMID- 27719774
TI  - Commentary on a Cochrane Review of Diet and Exercise Interventions to Prevent
      Excessive Gestational Weight Gain.
AB  - Excessive weight gain during pregnancy is associated with poor maternal and
      neonatal health outcomes. A Cochrane Review found that healthful diet and/or
      exercise interventions reduced the risk of excessive gestational weight gain on
      average by 20%. The largest reduction occurred with combined diet and supervised
      exercise interventions.

PMID- 27719775
TI  - Nursing Care of Pregnant Muslim Women During Ramadan.
AB  - There are approximately 3.3 million people of the Muslim faith living in the
      United States. This article explores how Muslim women observe their religious
      beliefs during pregnancy and discusses implications for nursing care of pregnant
      Muslim women during Ramadan. Although pregnant Muslim women can be exempt from
      fasting, many still choose to fast during Ramadan. Factors that influence a
      woman's decision to fast include gravity and parity, maternal education, maternal
      age, body mass index, comprehension of Islamic Law, and gestational trimester.
      Nurses can tailor their care of pregnant Muslim women to include episodes of
      fasting and help them make informed decisions regarding fasting during Ramadan.

PMID- 27719776
TI  - Improving Breastfeeding Support by Understanding Women's Perspectives and
      Emotional Experiences of Breastfeeding.
AB  - Exclusive breastfeeding for at least 6 months is universally acknowledged as the
      optimal means of infant nutrition. However, current studies show that most women
      are not following this recommendation. Many studies address the issue of
      increasing breastfeeding rates, but fewer explore the perspectives and
      experiences of breastfeeding women. In this article we review the literature and
      identify common themes in women's breastfeeding experiences. Nurses and other
      health care providers stand to help or hinder breastfeeding women, and they must
      be aware of and sensitive to women's personal experiences and perspectives to
      understand how to best promote and support women in their attempts to meet their
      breastfeeding goals.

PMID- 27719777
TI  - A Literature Review on the Practice of Placentophagia.
AB  - Placentophagia (consuming the placenta) has historically not been a common
      practice among humans. Over the past few decades the practice has gained
      attention as more women, particularly educated, middle-class, White American
      women, choose to partake in this practice. Purported benefits of placentophagia
      include pain relief, increased breast milk production, and decreased risk of
      postpartum depression; however, there is a lack of evidence to support these
      claims. The placenta can be consumed raw, cooked, or encapsulated; it can be used
      for keepsakes; or it can be used to make topical applications such as
      dermatologic creams and hair-growth products. Placentophagia has typically been
      viewed as a personal choice, resulting in little rigorous scientific research on
      the topic. More research is necessary to determine if the purported health
      benefits of placentophagia are proven.

PMID- 27719778
TI  - Assessment and Care of Childbearing Women With Severe and Persistent Mental
      Illness.
AB  - Severe and persistent mental illness (SPMI) refers to complex mood disorders that
      include major depressive disorder with or without psychosis; severe anxiety
      disorders resistant to treatment; affective psychotic disorders including bipolar
      affective disorder, schizophrenia, and schizoaffective disorder; and other
      nonaffective subtypes of schizophrenia. SPMIs affect 1 in 17 people and are among
      the leading causes of disability and impaired health-related quality of life in
      the United States. Caring for childbearing women with preexisting SPMI can be
      challenging for maternal-child health clinicians. This article provides an
      overview of SPMI during pregnancy and challenges for clinicians, including early
      identification, accuracy of diagnoses, and appropriate management through care
      coordination among an interdisciplinary team that includes obstetric providers,
      psychiatrists, nurses, and others.

PMID- 27719779
TI  - von Willebrand disease in pregnancy.
AB  - von Willebrand disease is the most prevalent inherited bleeding disorder,
      affecting up to 1.3% of the population. It is caused by a defect or deficiency of
      the von Willebrand factor. Women with the condition may not be aware of their
      condition at the time of childbirth, but they are at high risk of postpartum
      hemorrhage even days after birth. In this article we briefly review the condition
      and specific considerations for the antepartum, intrapartum, and postpartum
      phases. It is important for nurses who care for women during childbirth to have a
      keen understanding of this condition.

PMID- 27719781
TI  - A Nonhormonal Treatment for Moderate to Severe Vasomotor Symptoms of Menopause.
AB  - It is estimated that up to 80% of women experience symptoms related to declining
      estrogen levels that occur with menopause. The most common bothersome symptoms
      reported by women during and after this transition are vasomotor symptoms, which
      can include hot flashes, flushing, night sweats, and sleep disturbances. These
      symptoms are the most common reason women seek care during menopause. Until
      recently, the mainstay of treatment and symptom relief has been estrogen
      supplementation. In 2013, the U.S. Food and Drug Administration approved
      paroxetine, a low-dose selective serotonin reuptake inhibitor, as the first
      nonhormonal treatment for moderate to severe vasomotor symptoms of menopause.
      This article provides an overview of the use of paroxetine to treat vasomotor
      symptoms of menopause, including potential adverse reactions, special
      considerations for use, and implications for nursing practice.

PMID- 27719780
TI  - Cue-Based Feeding in the NICU.
AB  - In NICU settings, caring for neonates born as early as 23 weeks gestation
      presents unique challenges for caregivers. Traditionally, preterm infants who are
      learning to orally feed take a predetermined volume of breast milk or formula at
      scheduled intervals, regardless of their individual ability to coordinate each
      feeding. Evidence suggests that this volume-driven feeding model should be
      replaced with a more individualized, developmentally appropriate practice.
      Evidence from the literature suggests that preterm infants fed via cue-based
      feeding reach full oral feeding status faster than their volume-feeding
      counterparts and have shorter lengths of stay in the hospital. Changing practice
      to infant-driven or cue-based feedings in the hospital setting requires staff
      education, documentation, and team-based communication.

PMID- 27719782
TI  - Inside the Eyes of a Mother With Addiction.

PMID- 27719783
TI  - Editorial overview: Systems neuroscience 2016.

PMID- 27719784
TI  - ?

PMID- 27719785
TI  - ?

PMID- 27719786
TI  - [Refusal of nursing care, the legal perspective].
AB  - The refusal of nursing care forms part of the freedom offered to anyone wanting
      to refuse, consciously and knowingly, any form of nursing care such as washing,
      the taking of medication or hospitalisation. However, limits are fixed by law as
      well as by case law. Are we totally free in the expression of our will?

PMID- 27719787
TI  - [Nursing ethics in the face of the refusal of nursing care].
AB  - Caregivers can find themselves faced with a refusal of nursing care. A number of
      questions are then raised. While it is firstly important to understand the
      reasons for this refusal and what is at stake for the patient, there are a number
      of nursing strategies in place, not least of all dialogue and analysis. The role
      of the multi-disciplinary team is essential in such situations.

PMID- 27719788
TI  - [The refusal of nursing care by the families].
AB  - Caregiving is complex. While it is not easy to admit that the process can be
      refused by the patient, it is no easier when it is refused by the patient's
      family. Accepting this fact is however an essential stage in the relational and
      care processes. The family must therefore be supported by professionals in order
      to be able to make an enlightened choice.

PMID- 27719789
TI  - [Remaining a caregiver in the face of a refusal of nursing care].
AB  - Caregivers working with elderly people often find themselves in a difficult
      position when faced with the refusal of nursing care, whether or not the patient
      presents cognitive disorders. The nurses from the mobile geriatrics team of
      Rennes university hospital are regularly asked to help the caregiving teams in
      such situations. Refusals may concern washing, medication, eating, moving to an
      armchair, the organisation of physical aids or human assistance after discharge
      or transfer to a nursing home.

PMID- 27719790
TI  - [Professionals' training and refusal of nursing care].
AB  - A patient's refusal of nursing care concerns the caregivers. Future professionals
      must be prepared for it and student nurses are trained to deal with such
      situations. It is also important to empower patients and support them in their
      choice. This article presents the example of the Haute Ecole Robert Schuman in
      Libramont, Belgium.

PMID- 27719791
TI  - [A nursing career caring for children].
AB  - Celine Crouvisier always knew she wanted to work with babies and resolved to
      apply herself in secondary school in order to be able to go on to train as a
      child health nurse.

PMID- 27719792
TI  - [E-health benefiting wounds and healing].
AB  - The treatment of wounds forms a major part of nurses' practice in patients'
      homes. The choice of dressing requires real expertise drawing notably on
      collaborative approaches and the sharing of the patient's records. Based on this
      observation, Laurent Klein, a private practice nurse, designed and developed an e
      health tool aimed specifically at the treatment of wounds. A real nursing success
      story which has helped to improve the quality of care.

PMID- 27719793
TI  - [Mindfulness meditation, a source of professional wellbeing].
AB  - Mindfulness meditation, by focusing attention on what we are experiencing,
      improves personal wellbeing which is then expressed in caregivers' professional
      practices. Nurses who practise mindfulness will be better positioned to help
      their patients.

PMID- 27719795
TI  - [Concepts boosting the clinical impact in early neurological rehabilitation].
AB  - Vaudois university hospital in Lausanne, Switzerland, has an acute neurological
      rehabilitation unit. An interdisciplinary team cares for patients with brain
      injuries after their transfer from intensive care. In this context, nurses base
      their practice on different concepts and techniques for introducing early
      neurological rehabilitation into each care procedure.

PMID- 27719794
TI  - [The eb2(r) dummy, a therapeutic patient education tool in ENT surgery].
AB  - The day-to-day management and support of patients undergoing a total laryngectomy
      has led multi-disciplinary nursing teams to create a therapeutic patient
      education programme aiming to improve the quality of care and the autonomy of
      these people. In this context, the eb2(r) dummy is an essential tool.

PMID- 27719796
TI  - [Nursing practice in the face of a potentially suspect situation].
AB  - Nurses are rarely confronted with potentially criminal situations in their
      professional practice. The nursing culture does not prepare them especially for
      such cases, nor for the actions to take to preserve a scene which may contain
      valuable clues in the event of any legal proceedings. Sometimes contradictory to
      nurses' reflexes when dealing with emergencies, some basic precautions are
      nevertheless essential.

PMID- 27719797
TI  - ?

PMID- 27719798
TI  - Nursing Procedures in Dealing with Haemorrhagic Shock.
AB  - Sophie assesses a patient whose condition is deteriorating. She manages the
      critical situation in conjunction with the doctor on duty.

PMID- 27719799
TI  - ?

PMID- 27719800
TI  - ?

PMID- 27719801
TI  - ?

PMID- 27719802
TI  - Past, present and future of immunology in Mainz.

PMID- 27719803
TI  - Giants in Chest Medicine: James E. Dalen, MD, MPH, ScD (hon), Master FCCP.

PMID- 27719804
TI  - It's Not Rio but CHEST's Cough Guidelines Win Gold.

PMID- 27719805
TI  - The Importance of Being Adaptable: Developing Guidelines for Lung Nodule
      Evaluation in Asia.

PMID- 27719806
TI  - Anti-IL-5 for Severe Asthma: Aiming High to Achieve Success.

PMID- 27719807
TI  - Procalcitonin in Severe Community-Acquired Pneumonia: Some Precision Medicine
      Ready for Prime Time.

PMID- 27719812
TI  - Lung Ultrasonography in Diagnosis of Transient Tachypnea of the Newborn:
      Limitations and Pitfalls.

PMID- 27719813
TI  - Response.

PMID- 27719814
TI  - Management of Retrievable Inferior Vena Cava Filters.

PMID- 27719815
TI  - Response.

PMID- 27719816
TI  - Response.

PMID- 27719817
TI  - Warfarin for Atrial Fibrillation in Patients With End-Stage Renal Disease: The
      Problem of Observational Studies.

PMID- 27719818
TI  - Using the Proper Analytical Tools When Evaluating the Role of Midodrine in
      Resolving Septic Shock.

PMID- 27719819
TI  - Response.

PMID- 27719820
TI  - Endoscopic Ultrasound Training for Pulmonologists.

PMID- 27719821
TI  - Response.

PMID- 27719823
TI  - Correction to Grade in: Antithrombotic Therapy for VTE Disease: CHEST Guideline
      and Expert Panel Report.

PMID- 27719822
TI  - Time for a New Consensus on Lung Ultrasonography.

PMID- 27719825
TI  - Correction to data in: The Presence of Diffuse Alveolar Damage on Open Lung
      Biopsy Is Associated With Mortality in Patients With Acute Respiratory Distress
      Syndrome: A Systematic Review and Meta-Analysis.

PMID- 27719824
TI  - Notice of Retraction: Mechanical Ventilation as a Therapeutic Tool to Reduce ARDS
      Incidence. (Chest. 2015;148(6):1396-1404).

PMID- 27719826
TI  - A Pregnant Woman in the Third Trimester Diagnosed With Acute Respiratory Failure
      and Severe Lower-Extremity Edema.

PMID- 27719827
TI  - A 66-Year-Old Man With Mediastinal Mass and Dyspnea.
AB  - A 66-year-old man presented with dry cough and shortness of breath on exertion of
      6 months' duration. There were no complaints of fever and hemoptysis. His history
      was significant for recurrent episodes of respiratory tract infections over the
      previous 4 years. He had also had episodes of recurrent otitis media and pus
      discharge from the left ear for 3 years, with progressive loss of hearing. There
      was no history of recurrent skin infections or diarrhea. He was treated
      symptomatically with antibiotics by local general practitioners. He was a
      nonsmoker and did not drink alcohol, and there was no history of environmental or
      occupational exposure. He had been known to have diabetes for 10 years. He had
      negative results for the presence of HIV and hepatitis B surface antigen.

PMID- 27719828
TI  - A 43-Year-Old Man With Daytime Sleepiness and a Heart Murmur.
AB  - A 43-year-old man was referred to our tertiary sleep center for the initiation of
      sleep apnea treatment. A prior diagnostic overnight polysomnography (Fig 1) had
      revealed an apnea-hypopnea index (AHI) of 22/h of sleep. The apneas were
      predominantly central (central AHI, 18.2/h; obstructive AHI, 3.8/h), more
      pronounced in the supine position (AHI supine, 36.6/h; AHI nonsupine, 11/h) and
      during non-rapid eye movement (non-REM) sleep (REM, 15.8/h; non-REM, 23.5/h). A
      continuous positive airway pressure (CPAP) trial in an outpatient setting had
      failed, as the fixed CPAP of 11 cm H2O was not tolerated by the patient because
      of a feeling of lightheadedness when wearing the mask. At referral, the patient
      complained about falling asleep in front of the computer in the afternoons
      despite regular bedtimes and 7 to 8 h of sleep per night. His Epworth Sleepiness
      Scale score was 11. He had no significant past history including cardiopulmonary
      disease. He was not taking any medication but had noticed a slow decline in
      general physical performance in the last year, with dyspnea (New York Heart
      Association class I) after running distances of 1 to 2 km. He had never
      experienced syncope. His family history was unremarkable.

PMID- 27719829
TI  - Deaths Related to Bronchial Arterial Embolization in Patients With Cystic
      Fibrosis: Three Cases and an Institutional Review.
AB  - Cystic fibrosis (CF) patients are at risk for life-threatening hemoptysis,
      sometimes necessitating bronchial arterial embolization (BAE). Spinal artery
      embolization and pulmonary infarction are commonly cited procedural risks, yet
      respiratory failure and death are underappreciated. We conducted a retrospective
      institutional review of our outcomes after BAE for hemoptysis in CF and present
      three cases highlighting this complication. From 2007 to 2015, 12 patients
      underwent 17 BAE procedures for hemoptysis at our institution. Three patients
      experienced respiratory failure and died within 3 months of BAE. Nonsurvivors had
      significantly lower baseline FEV1 values than survivors (21.8% vs 52.6%, P <
      .05). BAE as a treatment for life-threatening hemoptysis may precipitate
      respiratory failure in end-stage CF and should accelerate the evaluation for lung
      transplantation. Institutions should reevaluate their BAE practices to ensure
      preservation of the bronchial circulation, which contributes to gas exchange in
      these patients.

PMID- 27719830
TI  - Pulmonary Artery Invasion Caused by Mycobacterium tuberculosis.
AB  - Extrapulmonary tuberculosis refers to Mycobacterium tuberculosis involving organs
      other than the lungs (eg, pleura, lymph nodes, genitourinary tract, abdomen,
      skin, joints and bones, or meninges). In non-HIV-endemic areas, where
      reactivation is the predominant mechanism of tuberculosis, pleural involvement
      occurs in 4% of cases. We present an extremely rare case of a 62-year-old
      immunocompetent patient with pleural tuberculosis confirmed by surgical pleural
      biopsies, who presented with a large mediastinal mass and evidence of pulmonary
      artery invasion on CT scanning and endobronchial ultrasonography imaging,
      highlighting a unique and malignant-like character of the disease.

PMID- 27719831
TI  - Psychologic theories in functional neurologic disorders.
AB  - In this chapter we review key psychologic theories that have been mooted as
      possible explanations for the etiology of functional neurologic symptoms,
      conversion disorder, and hysteria. We cover Freudian psychoanalysis and later
      object relations and attachment theories, social theories, illness behavior,
      classic and operant conditioning, social learning theory, self-regulation theory,
      cognitive-behavioral theories, and mindfulness. Dissociation and modern cognitive
      neuroscience theories are covered in other chapters in this series and, although
      of central importance, are omitted from this chapter. Our aim is an overview with
      the emphasis on breadth of coverage rather than depth.

PMID- 27719833
TI  - Voluntary or involuntary? A neurophysiologic approach to functional movement
      disorders.
AB  - Patients with functional movement disorders (FMD) experience movements as
      involuntary that share fundamental characteristics with voluntary actions. This
      apparent paradox raises questions regarding the possible sources of a subjective
      experience of action. In addition, it poses a yet unresolved diagnostic
      challenge, namely how to describe or even quantify this experience in a
      scientifically and clinically useful way. Here, we describe recent experimental
      approaches that have shed light on the phenomenology of action in FMD. We first
      outline the sources and content of a subjective experience of action in healthy
      humans and discuss how this experience may be created in the brain. Turning to
      FMD, we describe implicit, behavioral measures that have revealed specific
      abnormalities in the awareness of action in FMD. Based on these abnormalities, we
      propose a potential, new solution to the paradox of volition in FMD.

PMID- 27719832
TI  - Charcot, hysteria, and simulated disorders.
AB  - Jean-Martin Charcot (1825-1893) was the 19th-century's premier international
      neurologist. One of his areas of focused interest was the neurologic disorder,
      hysteria, a condition with distinctive neurologic signs, but no established
      structural lesions identified at autopsy. Charcot considered hysteria as a
      physiologic disorder that affected specific neuroanatomic areas of the brain
      comparable to the same areas that were damaged by structural neurologic disorders
      provoking the same or similar signs. He considered hysteria primarily a
      hereditary disorder, but environmental factors including physical and emotional
      stress served as provoking factors. Charcot drew the strict distinction between
      hysteria and consciously simulated neurologic disorders, although he was keenly
      aware that the two disorders could occur in the same patients or be difficult to
      distinguish at times. He developed specific experimental techniques to separate
      hysteria from simulation. His studies of hysteria and simulation offer a basis
      for studies of functional neurologic disorders applicable to the 21st century.

PMID- 27719834
TI  - Neurobiologic theories of functional neurologic disorders.
AB  - Although neurobiologic theories to explain functional neurologic symptoms have a
      long history, a relative lack of interest in the 20th century left them far
      behind neurobiologic understanding of other illness. Here we review the proposals
      for neurobiologic mechanisms of functional neurologic symptoms that have been
      made over time and consider how they might inform our diagnostic and treatment
      methods, and how they integrate with psychologic formulations of functional
      symptoms. Modern approaches map on to recent developments in theoretic models of
      brain function, and suggest a key role for processes affecting attention,
      beliefs/expectations, and a resultant impairment of sense of agency.

PMID- 27719835
TI  - Stress, childhood trauma, and cognitive functions in functional neurologic
      disorders.
AB  - Conversion disorder (CD) has traditionally been ascribed to psychologic factors
      such as trauma, stress, or emotional conflict. Although reference to the
      psychologic origin of CD has been removed from the criteria list in DSM-5, many
      theories still incorporate CD as originating from adverse events. This chapter
      provides a critical review of the literature on stressful life events in CD and
      discusses current cognitive and neurobiologic models linking psychologic
      stressors with conversion symptomatology. In addition, we propose a neurobiologic
      stress model integrating those cognitive models with neuroendocrine stress
      research and propose that stress and stress-induced changes in hypothalamus
      pituitary-adrenal (HPA) axis function may result in cognitive alterations, that
      in turn contribute to experiencing conversion symptoms. Experimental studies
      indeed suggest that basal as well as stress-induced changes in HPA axis
      responding lead to alterations in attentional processing in CD. Although those
      changes are stronger in traumatized patients, similar patterns have been observed
      in patients who do not report a history of traumatic events. We conclude that,
      whereas adverse events may play an important role in many cases of CD, a
      substantial proportion of patients do not report a history of traumatization or
      recent stressful events. Studies integrating effects of stress on cognitive
      functioning in CD are scarce. We propose that, instead of focusing research on
      defining etiologic events in terms of symptom-eliciting events, future research
      should work towards an integrated mechanistic account, assessing alterations in
      cognitive and biologic stress systems in an integrated manner in patients with
      CD. Such an account may not only serve early symptom detection, it might also
      provide a starting point for better-targeted interventions.

PMID- 27719836
TI  - Do (epi)genetics impact the brain in functional neurologic disorders?
AB  - Advances in neuropsychiatric research are supposed to lead to significant
      improvements in understanding functional neurologic disorders and their
      diagnosis. However, epigenetic and genetic research on conversion disorders and
      somatoform disorders is only at its start. This review demonstrates the current
      state within this field and tries to bridge a gap from what is known on gene
      stress interactions in other psychiatric disorders like depression. The etiology
      of conversion disorders is hypothesized to be multifactorial. These
      considerations also suggest that potential etiologic factors lead to alterations
      in brain function, either episodically or chronically, eventually leading to
      structural brain changes. In particular, the knowledge of how the environment
      influences brain structure and function, e.g., via epigenetic regulation, may be
      interesting for future research in functional neurologic disorders. Reviewing the
      literature results in evidence that childhood adversities play a role in the
      development of functional neurologic disorders, whereby at present no reports
      exist about the interactive effect between childhood adversity and genetic
      factors or about the impact of epigenetics.

PMID- 27719837
TI  - Assessment of patients with functional neurologic disorders.
AB  - We describe an overall approach and structure to the clinical assessment of the
      patient with a functional neurologic disorder. Whilst the primary purpose of the
      assessment is to make a diagnosis and develop a treatment plan, we believe the
      assessment also plays a key role in treatment in its own right, as it sets a tone
      and context for future clinical interactions. We aim to set up an atmosphere of
      collaboration based on taking the patient's problems seriously, and emphasizing
      that all facets of the patient's presentation - physical, psychologic, and social
      - are of importance. Patients with functional disorders can be perceived as
      difficult to help and yet with the correct approaches we believe the consultation
      can be much more satisfying for both patient and doctor. Finally, we discuss and
      list some of the common diagnostic pitfalls in the assessment of functional
      neurologic disorders, looking at features that lead to erroneous diagnosis of
      neurologic disease (such as old age, la belle indifference, and lack of
      psychiatric comorbidity) and an erroneous diagnosis of a functional disorder
      (such as "bizarre" gait in stiff-person syndrome).

PMID- 27719838
TI  - The classification of conversion disorder (functional neurologic symptom
      disorder) in ICD and DSM.
AB  - The name given to functional neurologic symptoms has evolved over time in the
      different editions of the International Classification of Diseases (ICD) and the
      Diagnostic and Statistical Manual of Mental Disorders (DSM), reflecting a gradual
      move away from an etiologic conception rooted in hysterical conversion to an
      empiric phenomenologic one, emphasizing the central role of the neurologic
      examination and testing in demonstrating that the symptoms are incompatible with
      recognized neurologic disease pathophysiology, or are internally inconsistent.

PMID- 27719839
TI  - Neurologic diagnostic criteria for functional neurologic disorders.
AB  - The diagnosis of functional neurologic disorders can be challenging. In this
      chapter we review the diagnostic criteria and rating scales reported for
      functional/psychogenic sensorimotor disturbances, psychogenic nonepileptic
      seizures (PNES) and functional movement disorders (FMD). A recently published
      scale for sensorimotor signs has some limitations, but may help in the diagnosis,
      and four motor and two sensory signs have been reported as highly reliable. There
      is good evidence using eight specific signs for the differentiation of PNES from
      seizures. Recently, diagnostic criteria were developed for PNES; their
      sensitivity and specificity need to be evaluated. The definitive diagnosis of
      PNES can be made by recording typical positive features during the spells, and in
      a low proportion of cases, where the distinction with an organic etiology cannot
      easily be done, a normal electroencephalogram suggests the diagnosis. FMD
      diagnosis relies on diagnostic criteria, which have been refined over time and
      may be supplemented by laboratory tests in some phenotypes. Rating scales for
      PNES and FMD could be useful for severity measures, but several limitations
      remain to be addressed.

PMID- 27719841
TI  - Functional tremor.
AB  - Functional tremor is the commonest reported functional movement disorder. A
      confident clinical diagnosis of functional tremor is often possible based on the
      following "positive" criteria: a sudden tremor onset, unusual disease course,
      often with fluctuations or remissions, distractibility of the tremor if attention
      is removed from the affected body part, tremor entrainment, tremor variability,
      and a coactivation sign. Many patients show excessive exhaustion during
      examination. Other somatizations may be revealed in the medical history and
      patients may show additional functional neurologic symptoms and signs. In cases
      where the clinical diagnosis remains challenging, providing a "laboratory
      supported" level of certainty aids an early positive diagnosis. In rare cases, in
      which the distinction from Parkinson's disease is difficult, dopamine transporter
      single-photon emission computed tomography (DAT-SPECT) can be indicated.

PMID- 27719840
TI  - Functional limb weakness and paralysis.
AB  - Functional (psychogenic) limb weakness describes genuinely experienced limb power
      or paralysis in the absence of neurologic disease. The hallmark of functional
      limb weakness is the presence of internal inconsistency revealing a pattern of
      symptoms governed by abnormally focused attention. In this chapter we review the
      history and epidemiology of this clinical presentation as well as its subjective
      experience highlighting the detailed descriptions of authors at the end of the
      19th and early 20th century. We discuss the relevance that physiological triggers
      such as injury and migraine and psychophysiological events such as panic and
      dissociation have to understanding of mechanism and treatment. We review many
      different positive diagnostic features, their basis in neurophysiological testing
      and present data on sensitivity and specificity. Diagnostic bedside tests with
      the most evidence are Hoover's sign, the hip abductor sign, drift without
      pronation, dragging gait, give way weakness and co-contraction.

PMID- 27719842
TI  - Functional dystonia.
AB  - Although currently lacking a sensitive and specific electrophysiologic battery
      test, functional (psychogenic) dystonia can sometimes be diagnosed with
      clinically definite certainty using available criteria. Certain regional
      phenotypes have been recognized as distinctive, such as unilateral lip and jaw
      deviation, laterocollis with ipsilateral shoulder elevation and contralateral
      shoulder depression, fixed wrist and finger flexion with relative sparing of the
      thumb and index fingers, and fixed foot plantar flexion and inversion. The
      pathophysiologic abnormalities in functional dystonia overlap substantially with
      those of organic dystonia, with similar impairments in cortical and spinal
      inhibition and somatosensory processing, but with emerging data suggesting
      abnormalities in regional blood flow and activation patterns on positron emission
      tomography and functional magnetic resonance imaging, respectively. Management of
      functional dystonia begins with compassionate and assertive debriefing of the
      diagnosis to ensure full acceptance by the patient, a critical step in enhancing
      the likelihood of success with physical rehabilitation, and psychodynamic or
      cognitive therapy. Physical therapy, with or without cognitive behavioral
      therapy, appears to be of benefit but has not yet been examined in a controlled
      fashion. While the prognosis remains grim for a substantial majority of patients,
      partly stemming from restricted mobility, delayed diagnosis, and inappropriate
      pharmacotherapy, early recognition and initiation of therapy stand to minimize
      iatrogenic harm and unnecessary laboratory investigations, and potentially reduce
      the long-term neurologic disability.

PMID- 27719843
TI  - Functional jerks, tics, and paroxysmal movement disorders.
AB  - Functional jerks are among the most common functional movement disorders. The
      diagnosis of functional jerks is mainly based on neurologic examination revealing
      specific positive clinical signs. Differentiation from other jerky movements,
      such as tics, organic myoclonus, and primary paroxysmal dyskinesias, can be
      difficult. In support of a functional jerk are: acute onset in adulthood,
      precipitation by a physical event, variable, complex, and inconsistent
      phenomenology, suggestibility, distractibility, entrainment and a
      Bereitschaftspotential preceding the movement. Although functional jerks and tics
      share many similarities, characteristics differentiating tics from functional
      jerks are: urge preceding the tic, childhood onset, rostrocaudal development of
      the symptoms, a positive family history of tics, attention-deficit hyperactivity
      disorder or obsessive-compulsive symptoms, and response to dopamine antagonist
      medication. To differentiate functional jerks from organic myoclonus,
      localization of the movements can give direction. Further features in support of
      organic myoclonus include: insidious onset, simple and consistent phenomenology,
      and response to benzodiazepines or antiepileptic medication. Primary paroxysmal
      dyskinesias and functional jerks share a paroxysmal nature. Leading in the
      differentiation between the two are: a positive family history, in combination
      with video recordings revealing a consistent symptom pattern in primary
      paroxysmal dyskinesias. In this chapter functional jerks and their differential
      diagnoses will be discussed in terms of epidemiology, symptom characteristics,
      disease course, psychopathology, and supportive neurophysiologic tests.

PMID- 27719844
TI  - Neurologic approaches to hysteria, psychogenic and functional disorders from the
      late 19th century onwards.
AB  - The history of functional neurologic disorders in the 20th century from the point
      of view of the neurologist is U-shaped. A flurry of interest between the 1880s
      and early 1920s gave way to lack of interest, skepticism, and concern about
      misdiagnosis. This was mirrored by increasing professional and geographic
      divisions between neurology and psychiatry after the First World War. In the
      1990s the advent of imaging and other technology highlighted the positive nature
      of a functional diagnosis. Having been closer in the early 20th century but later
      more separate, these disorders are now once again the subject of academic and
      clinical interest, although arguably still very much on the fringes of neurology
      and neuropsychiatry. Revisiting older material provides a rich source of ideas
      and data for today's clinical researcher, but also offers cautionary tales of
      theories and treatments that led to stagnation rather than advancement of the
      field. Patterns of treatment do have a habit of repeating themselves, for
      example, the current enthusiasm for transcranial magnetic stimulation compared to
      the excitement about electrotherapy in the 19th century. For these reasons, an
      understanding of the history of functional disorders in neurology is arguably
      more important than it is for other areas of neurologic practice.

PMID- 27719845
TI  - Psychogenic (functional) parkinsonism.
AB  - Psychogenic parkinsonism (PP), although often quite disabling, is one of the
      least commonly reported subtypes of psychogenic movement disorders. There are
      certain features that help distinguish PP from idiopathic Parkinson's disease,
      such as abrupt onset, early disability, bilateral shaking and slowness,
      nondecremental slowness when performing repetitive movements, voluntary
      resistance against passive movement without cogwheel rigidity, distractibility,
      "give-way" weakness, stuttering speech, bizarre gait, and a variety of behavioral
      symptoms. While the diagnosis of PP is clinical, functional imaging evaluating
      the integrity of nigrostriatal pathways can help distinguish PP from other types
      of parkinsonism. PP can coexist in patients with organic parkinsonism, adding to
      the challenge of making a diagnosis of PP. Being cognizant of the clinical signs
      of psychogenic movement disorders, including PP, will lead to earlier diagnosis
      and hopefully improved outcomes.

PMID- 27719846
TI  - Functional gait disorder.
AB  - Gait disorder is a common accompaniment of functional neurologic disorders. The
      diagnosis of a functional or psychogenic gait is complex. It requires a sound
      knowledge of the range of phenomenology observed in organic movement disorders,
      the ability to evaluate and diagnose nonmovement disorder neurologic symptoms and
      signs, but additionally knowledge of potential musculoskeletal causes of gait
      disturbance. A stepwise approach to the analysis of the phenomenology and
      separation into four (sometimes overlapping) psychogenic gait syndromes is
      suggested to aid diagnosis: (1) movement disorder mimics; (2) neurologic
      (nonmovement disorder) mimics; (3) musculoskeletal or biomechanical mimics; and
      (4) isolated disequilibrium or balance disorders. Accurate diagnosis can lead to
      effective therapy.

PMID- 27719847
TI  - Functional sensory symptoms.
AB  - Functional (psychogenic) sensory symptoms are those in which the patient
      genuinely experiences alteration or absence of normal sensation in the absence of
      neurologic disease. The hallmark of functional sensory symptoms is the presence
      of internal inconsistency revealing a pattern of symptoms governed by abnormally
      focused attention. In this chapter we review the history of this area, different
      clinical presentations, diagnosis (including sensitivity of diagnostic tests),
      treatment, experimental studies, and prognosis. Altered sensation has been a
      feature of "hysteria" since descriptions of witchcraft in the middle ages. In the
      19th century hysteric sensory stigmata were considered a hallmark of the
      condition. Despite this long history, relatively little attention has been paid
      to the topic of functional sensory disturbance, compared to functional limb
      weakness or functional movement disorders, with which it commonly coexists. There
      are recognizable clinical patterns, such as hemisensory disturbance and sensory
      disturbance finishing at the groin or shoulder, but in keeping with the
      literature on reliability of sensory signs in neurology in general, the evidence
      suggests that physical signs designed to make a positive diagnosis of functional
      sensory disorder may not be that reliable. There are sensory symptoms which are
      unusual but not functional (such as synesthesia and allochiria) but also
      functional sensory symptoms (such as complete loss of all pain) which are most
      unusual and probably worthy of independent study.

PMID- 27719848
TI  - Nonepileptic seizures - subjective phenomena.
AB  - Psychogenic nonepileptic seizures (PNES) superficially resemble epileptic
      seizures or syncope and most patients with PNES are initially misdiagnosed as
      having one of the latter two types of transient loss of consciousness. However,
      evidence suggests that the subjective seizure experience of PNES and its main
      differential diagnoses are as different as the causes of these three disorders.
      In spite of this, and regardless of the fact that PNES are considered a mental
      disorder in the current nosologies, research has only given limited attention to
      the subjective symptomatology of PNES. Instead, most phenomenologic research has
      focused on the visible manifestations of PNES and on physiologic parameters,
      neglecting patients' symptoms and experiences. This chapter gives an overview of
      qualitative and quantitative studies providing insights into subjective symptoms
      associated with PNES, drawing on a wide range of methodologies (questionnaires,
      self-reports, physiologic measures, linguistic analyses, and neuropsychologic
      experiments). After discussing the scope and limitations of these approaches in
      the context of this dissociative phenomenon, we discuss ictal, peri-ictal and
      interictal symptoms described by patients with PNES. We particularly focus on
      impairment of consciousness. PNES emerges as a clinically heterogeneous
      condition. We conclude with a discussion of the clinical significance of
      particular subjective symptoms for the engagement of patients in treatment, the
      formulation of treatment, and prognosis.

PMID- 27719849
TI  - Nonepileptic seizures - objective phenomena.
AB  - This chapter describes the evaluation process for the diagnosis of psychogenic
      nonepileptic seizures (PNES), which is determined based on concordance of the
      composite evidence available, including historic and physical exam findings,
      seizure semiology, and ictal/interictal electroencephalogram (EEG). No single
      clinical feature is pathognomonic of PNES. The diagnosis of PNES can be at times
      challenging, such as when seizure documentation on video-EEG cannot be readily
      achieved. A multicomponent approach to the diagnosis of PNES, with use of all
      available evidence, may facilitate diagnosis and then care of patients with PNES.
      Emerging evidence supports the use of symptom identification by the patient as
      part of the treatment of these patients. With advances in diagnostic methods and
      criteria, the diagnosis of PNES can be made reliably.

PMID- 27719850
TI  - A brief history of hysteria: From the ancient to the modern.
AB  - In this paper we discuss the history of hysteria from the Babylonian and Assyrian
      texts through to the situation as it appears to us at the end of the 19th
      century. We note the shifting emphasis on causation, earlier ideas being linked
      to uterine theories, later speculations moving to the brain, and then the mind.
      We note the persistence of the condition referred to as hysteria over the
      millennia and the fascination that the condition has held for physicians,
      neurologists, and psychiatrists since the origins of known medical texts.

PMID- 27719851
TI  - Psychogenic nonepileptic seizures: EEG and investigation.
AB  - In the investigation of psychogenic nonepileptic seizures (PNES), the main
      differential diagnoses are between convulsive PNES and tonic-clonic seizures,
      between swoon PNES and syncope, and between pseudoabsence PNES and absence
      seizures. For the best diagnostic certainty, events must be captured, ideally
      using video-electroencephalogram (EEG), including an electrocardiographic
      channel. The "video" part of video-EEG allows EEG changes (or lack of them) to be
      interpreted in the appropriate clinical context. When the diagnosis is based on
      less good data (e.g., video alone or EEG alone), then the limitations and
      constraints of the tests should borne in mind, and a lesser degree of certainty
      must be accepted. Tests such as serum prolactin (PRL) level and postictal EEG
      should be regarded as adjunctive rather than definitive. Excluding additional
      epilepsy with a good probability is not possible using investigations alone. In
      particular, one standard interictal EEG recording is of little value in excluding
      additional epilepsy, though multiple or prolonged recordings may offer additional
      sensitivity.

PMID- 27719852
TI  - Functional coma.
AB  - Functional coma - here defined as a prolonged motionless dissociative attack with
      absent or reduced response to external stimuli - is a relatively rare
      presentation. In this chapter we examine a wide range of terms used to describe
      states of unresponsiveness in which psychologic factors are relevant to etiology,
      such as depressive stupor, catatonia, nonepileptic "pseudostatus," and factitious
      disorders, and discuss the place of functional or psychogenic coma among these.
      Historically, diagnosis of functional coma has sometimes been reached after
      prolonged investigation and exclusion of other diagnoses. However, as is the case
      with other functional disorders, diagnosis should preferably be made on the basis
      of positive findings that provide evidence of inconsistency between an apparent
      comatose state and normal waking nervous system functioning. In our review of
      physical signs, we find some evidence for the presence of firm resistance to eye
      opening as reasonably sensitive and specific for functional coma, as well as the
      eye gaze sign, in which patients tend to look to the ground when turned on to one
      side. Noxious stimuli such as Harvey's sign (application of high-frequency
      vibrating tuning fork to the nasal mucosa) can also be helpful, although patients
      with this disorder are often remarkably unresponsive to usually painful stimuli,
      particularly as more commonly applied using sternal or nail bed pressure. The use
      of repeated painful stimuli is therefore not recommended. We also discuss the
      role of general anesthesia and other physiologic triggers to functional coma.

PMID- 27719853
TI  - Functional and simulated visual loss.
AB  - Nonorganic visual loss (NOVL) is the cause of a large number of referrals to
      neurologists and ophthalmologists and is a frequent area of overlap between
      neurologists, ophthalmologists, and psychiatrists. NOVL is the presence of visual
      impairment without an organic cause for disease despite a thorough and
      comprehensive investigation. A diagnosis of NOVL requires both the absence of any
      findings on examination and proof of the integrity and functioning of the visual
      system. Although sometimes a challenging diagnosis to make, there are a number of
      techniques and maneuvers which can be utilized fairly easily, either at the
      bedside or in the clinic, to help determine if a patient has NOVL. In some
      instances specialized testing, such as formal visual field testing, optical
      coherence tomography, visual evoked responses, electroretinogram, and various
      imaging modalities (magnetic resonance imaging) are performed to help determine
      if the cause of visual loss is organic or nonorganic. Once a diagnosis of NOVL is
      made, treatment centers around reassurance of the patient, close follow-up, and,
      if necessary, referral to a psychiatrist, as these patients may have underlying
      psychiatric disorders and a preceding strong emotional event leading to the
      current symptoms, and may be more likely to develop depression and anxiety.

PMID- 27719854
TI  - Functional eye movement disorders.
AB  - Functional (psychogenic) eye movement disorders are perhaps less established in
      the medical literature than other types of functional movement disorders.
      Patients may present with ocular symptoms (e.g., blurred vision or oscillopsia)
      or functional eye movements may be identified during the formal examination of
      the eyes in patients with other functional disorders. Convergence spasm is the
      most common functional eye movement disorder, but functional gaze limitation,
      functional eye oscillations (also termed "voluntary nystagmus"), and functional
      convergence paralysis may be underreported. This chapter reviews the different
      types of functional eye movement abnormalities and provides a practical framework
      for their diagnosis and management.

PMID- 27719855
TI  - Functional facial and tongue movement disorders.
AB  - Functional movement disorders (FMDs) affecting the eyelids, tongue, and other
      facial muscles are often underrecognized because their phenomenology has not been
      fully characterized. Nevertheless, these disorders are more common than
      previously thought. In this chapter we will discuss the phenomenology as well as
      the clinical and instrumental diagnosis of facial FMDs. Facial FMDs should be
      considered when a patient exhibits any combination of the following features: (1)
      fixed unilateral facial contractions, especially with lower lip, with or without
      ipsilateral jaw involvement, of maximal severity at onset; (2) inconsistent
      features such as changes in side and pattern during or between examination; (3)
      associated somatoform or nonphysiologic sensory or motor findings; (4) reduction
      or abolition of facial spasm with distraction; (5) response to suggestion or
      psychotherapy; (6) rapid onset and/or spontaneous remissions; and (7) normal
      neurologic examination. Supportive features are young age, female gender, and
      associated medical conditions such as depression, headaches, facial pain,
      fibromyalgia, or irritable-bowel syndrome. Finally, the differential diagnosis
      with the organic counterparts will be also addressed, particularly with respect
      to blepharospasm, oromandibular dystonia, and hemifacial spasm.

PMID- 27719856
TI  - Functional auditory disorders.
AB  - There are a number of auditory symptom syndromes that can develop without an
      organic basis. Some of these, such as nonorganic hearing loss, affect populations
      similar to those presenting with functional somatosensory and motor symptoms,
      while others, such as musical hallucination, affect populations with a
      significantly different demographic and require different treatment strategies.
      Many of these conditions owe their origin to measurably abnormal peripheral
      sensory pathology or brain network activity, but their pathological impact is
      often due, at least in part, to overamplification of the salience of these
      phenomena. For each syndrome, this chapter briefly outlines a definition,
      demographics, investigations, putative mechanisms, and treatment strategies.
      Consideration is given to what extent they can be considered to have a functional
      basis. Treatments are in many cases pragmatic and rudimentary, needing more work
      to be done in integrating insights from behavioral and cognitive psychology to
      auditory neuroscience. The audiology literature has historically equated the term
      functional with malingering, although this perception is, thankfully, slowly
      changing. These disorders transcend the disciplines of audiology,
      otorhinolaryngology, neurology and psychiatry, and a multidisciplinary approach
      is often rewarding.

PMID- 27719857
TI  - Freud's hysteria and its legacy.
AB  - Though Freud was himself interested in neurologic disorders, the model of
      hysteria he developed - of the repression of painful experiences, and their
      conversion into physical symptoms - made the disorder psychiatric, as the
      increasingly complex explanations came to rely on the "meaning" of events, which
      could not easily be understood neurologically. This evolved to become a prototype
      for psychiatric illness more broadly, a model which, though challenged by the
      First World War, enjoyed great success, notably in the USA, dominating
      psychiatric thinking for most of the 20th century. Concerns about the empiric
      basis for his ideas latterly led to a rapid decline in their importance, however,
      exemplified by 1980's "etiologically neutral" DSM-III. Hysteria, now renamed
      conversion disorder, retained its Freudian explanation for another 30 years, but
      as psychiatry lost its faith in Freud, so psychiatrists stopped seeing the
      disorder he had made theirs, and returned it once more to neurology.

PMID- 27719858
TI  - Functional speech disorders: clinical manifestations, diagnosis, and management.
AB  - Acquired psychogenic or functional speech disorders are a subtype of functional
      neurologic disorders. They can mimic organic speech disorders and, although any
      aspect of speech production can be affected, they manifest most often as
      dysphonia, stuttering, or prosodic abnormalities. This chapter reviews the
      prevalence of functional speech disorders, the spectrum of their primary clinical
      characteristics, and the clues that help distinguish them from organic neurologic
      diseases affecting the sensorimotor networks involved in speech production.
      Diagnosis of a speech disorder as functional can be supported by sometimes
      rapidly achieved positive outcomes of symptomatic speech therapy. The general
      principles of such therapy are reviewed.

PMID- 27719859
TI  - Functional voice disorders: Clinical presentations and differential diagnosis.
AB  - In this chapter, an overview of the heterogeneous group of functional voice
      disorders is given, including the psychogenic voice disorder (PVD) and
      hyperfunctional or muscle tension voice disorder (MTVD) subgroups. Reference is
      made to prevalence and demographic data, with empiric evidence for psychosocial
      factors commonly associated with the onset and maintenance of these disorders.
      Clinical features that distinguish between the different presentations of PVD and
      MTVD are described. While there are some shared characteristics, key differences
      between these two subgroups indicate that PVD more closely resembles the
      psychogenic movement disorders and a range of other functional neurologic
      disorders. Assessment procedures and auditory-perceptual features of the voice
      that distinguish these disorders from the neurologically based voice disorders
      are discussed, with case examples highlighting ambiguous features that may
      influence differential diagnosis. The clinical profiles of PVD and MTVD affirm
      approaches to clinical management by speech-language pathologists that integrate
      symptomatic behavioral voice therapy with "top-down" models of counseling or
      psychotherapy. They also support the proposition that PVD may be construed as a
      subtype of functional neurologic disorders.

PMID- 27719860
TI  - Psychologic/functional forms of memory disorder.
AB  - In this chapter, we discuss the wide variety of patients who may attend a memory
      clinic or other health services presenting with memory symptoms but who do not
      have dementia. These diagnoses may include a wide range of neurologic and
      neuropsychiatric disorders; in this chapter we will focus on other causes of
      memory symptoms which may be labeled psychologic or functional, or be more
      obviously part of an established psychiatric disorder. We describe the
      differential categorization recently posited by Stone et al. (2015), and consider
      important aspects of assessment and management in these cases.

PMID- 27719861
TI  - Functional (dissociative) retrograde amnesia.
AB  - Retrograde amnesia is described as condition which can occur after direct brain
      damage, but which occurs more frequently as a result of a psychiatric illness. In
      order to understand the amnesic condition, content-based divisions of memory are
      defined. The measurement of retrograde memory is discussed and the dichotomy
      between "organic" and "psychogenic" retrograde amnesia is questioned. Briefly,
      brain damage-related etiologies of retrograde amnesia are mentioned. The major
      portion of the review is devoted to dissociative amnesia (also named psychogenic
      or functional amnesia) and to the discussion of an overlap between psychogenic
      and "brain organic" forms of amnesia. The "inability of access hypothesis" is
      proposed to account for most of both the organic and psychogenic (dissociative)
      patients with primarily retrograde amnesia. Questions such as why recovery from
      retrograde amnesia can occur in retrograde (dissociative) amnesia, and why long
      term new learning of episodic-autobiographic episodes is possible, are addressed.
      It is concluded that research on retrograde amnesia research is still in its
      infancy, as the neural correlates of memory storage are still unknown. It is
      argued that the recollection of episodic-autobiographic episodes most likely
      involves frontotemporal regions of the right hemisphere, a region which appears
      to be hypometabolic in patients with dissociative amnesia.

PMID- 27719862
TI  - Functional (psychogenic) dizziness.
AB  - Functional and psychiatric disorders that cause vestibular symptoms (i.e.,
      vertigo, unsteadiness, and dizziness) are common. In fact, they are more common
      than many well-known structural vestibular disorders. Neurologists and otologists
      are more likely to encounter patients with vestibular symptoms due to persistent
      postural-perceptual dizziness or panic disorder than Meniere's disease or
      bilateral vestibular loss. Successful approaches to identifying functional and
      psychiatric causes of vestibular symptoms can be incorporated into existing
      practices without much difficulty. The greatest challenge is to set aside
      dichotomous thinking that strongly emphasizes investigations of structural
      diseases in favor of a three-pronged approach that assesses structural,
      functional, and psychiatric disorders simultaneously. The pathophysiologic
      mechanisms underlying functional and psychiatric causes of vestibular symptoms
      are better understood than many clinicians realize. Research methods such as
      advanced posturographic analysis and functional brain imaging will push this
      knowledge further in the next few years. Treatment plans that include patient
      education, vestibular rehabilitation, cognitive and behavioral therapies, and
      medications substantially reduce morbidity and offer the potential for sustained
      remission when applied systematically. Diagnostic and therapeutic approaches are
      necessarily multidisciplinary in nature, but they are well within the purview of
      collaborative care teams or networks of clinicians coordinated with the
      neurologists and otologists whom patients consult first.

PMID- 27719863
TI  - Urologic symptoms and functional neurologic disorders.
AB  - The term functional urologic disorders covers a wide range of conditions related
      broadly to altered function rather than structure of the lower urinary tract,
      mainly of impaired urine voiding or storage. Confusingly, for a neurologic
      readership, these disorders of function may often be due to a urologic,
      gynecologic, or neurologic cause. However, there is a subset of functional
      urologic disorders where the cause remains uncertain and, in this chapter, we
      describe the clinical features of these disorders in turn: psychogenic urinary
      retention; Fowler's syndrome; paruresis (shy-bladder syndrome); dysfunctional
      voiding; idiopathic overactive bladder, and interstitial cystitis/bladder pain
      syndrome. Some of these overlap in terms of symptoms, but have become
      historically separated. Psychogenic urinary retention in particular has now
      largely been abandoned as a concept, in part because of the finding of specific
      urethral electromyogram findings in patients with this symptom now described as
      having Fowler's syndrome, and their successful treatment with sacral
      neurostimulation. In this chapter we review the poorly researched interface
      between these "idiopathic" functional urologic disorders and other functional
      disorders (e.g., irritable-bowel syndrome, fibromyalgia) as well as specifically
      functional neurologic disorders. We conclude that there may be a relationship and
      overlap between them and that this requires further research, especially in those
      idiopathic functional urologic disorders which involve disorders of the urethral
      sphincter (i.e., voluntary muscle).

PMID- 27719864
TI  - Epidemiology.
AB  - The epidemiology of functional neurologic disorders (FND) is complex and has been
      hampered over the years by a lack of clear definition, with previous definitions
      struggling with an uneasy mix of both physical and psychologic components. The
      recent changes in DSM-5 to a definition based on positive identification of
      physical symptoms which are incongruent and inconsistent with neurologic disease
      and the lack of need for any associated psychopathology represent a significant
      step forward in clarifying the disorder. On this basis, FND account for
      approximately 6% of neurology outpatient contacts and putative community
      incidence rates of 4-12 per 100 000 per annum. Comorbid neurologic disease occurs
      in around 10% of cases. The diagnosis is reliable, with revision rates less than
      5%. Of note, this revision rate was consistent prior to the widespread
      utilization of computed tomography and magnetic resonance imaging. FND symptoms
      are disabling and associated with significant distress. They are more common in
      women and have a peak incidence between the ages of 35 and 50; however the
      presentation is common in men and throughout the lifespan. The issues surrounding
      case definition, ascertainment, misdiagnosis, and risk factors are discussed in
      detail.

PMID- 27719865
TI  - Functional disorders of swallowing.
AB  - Swallowing involves complex coordination of the neuromuscular anatomy and
      physiology of the oropharynx and esophagus, controlled by the enteric and central
      nervous systems. Dysphagia is classified as either oropharyngeal or esophageal
      and results from mechanical or structural disturbances. Videofluoroscopy,
      fiberoptic endoscopic evaluation of swallowing, barium swallow, manometry, and
      endoscopy are common modalities utilized in diagnosis, but none is as important
      as a patient's history. Functional dysphagia is a diagnosis of exclusion and is
      based on Rome criteria. Its mechanism is unknown but potentially related to
      visceral hypersensitivity, inappropriate pain perception, or unidentified
      contraction abnormalities. Its management is mainly supportive; however, there is
      literature to suggest, but not confirm, benefit with the use of antidepressants.
      Continued understanding of functional dysphagia and other functional esophageal
      disorders, including globus sensation, will require further investigation into
      diagnostic algorithms and finding treatment methods.

PMID- 27719866
TI  - Pediatric functional neurologic symptoms.
AB  - Functional neurologic disorders (FND) of children have many similarities to those
      of adults, and there is a potential to learn much from the study of FND in
      children. In this chapter we discuss multiple aspects of pediatric FND. These
      include their frequency, historic features, the diagnosis, and controversies over
      the nature of FND and the "correct" name that should be used. We also discuss
      methods of informing the child and family of the diagnosis, treatment, and
      prognosis. FND of children typically affect girls in the 10-14-years age range.
      The presentation is often polysymptomatic, with pain and lethargy accompanying
      loss of motor function. A common situation is a perfectionistic child who has
      taken on too much in her academic, sporting, cultural, and social life. Some
      children respond readily to treatment, but others have a prolonged illness.

PMID- 27719867
TI  - Posttraumatic functional movement disorders.
AB  - Traumatic injury to the nervous system may account for a range of neurologic
      symptoms. Trauma location and severity are important determinants of the
      resulting symptoms. In severe head injury with structural brain abnormalities,
      the occurrence of trauma-induced movement disorders, most commonly hyperkinesias
      such as tremor and dystonia, is well recognized and its diagnosis
      straightforward. However, the association of minor traumatic events, which do not
      lead to significant persistent structural brain damage, with the onset of
      movement disorders is more contentious. The lack of clear clinical-neuroanatomic
      (or symptom lesion) correlations in these cases, the variable timing between
      traumatic event and symptom onset, but also the presence of unusual clinical
      features in a number of such patients, which overlap with signs encountered in
      patients with functional neurologic disorders, contribute to this controversy.
      The purpose of this chapter is to provide an overview of the movement disorders,
      most notably dystonia, that have been associated with peripheral trauma and focus
      on their unusual characteristics, as well as their overlap with functional
      neurologic disorders. We will then provide details on pathophysiologic views that
      relate minor peripheral injuries to the development of movement disorders and
      compare them to knowledge from primary organic and functional movement disorders.
      Finally, we will comment on the appropriate management of these disorders.

PMID- 27719868
TI  - Factitious disorders and malingering in relation to functional neurologic
      disorders.
AB  - Interest in malingering has grown in recent years, and is reflected in the
      exponential increase in academic publications since 1990. Although malingering is
      more commonly detected in medicolegal practice, it is not an all-or-nothing
      presentation and moreover can vary in the extent of presentation. As a nonmedical
      disorder, the challenge for clinical practice remains that malingering by
      definition is intentional and deliberate. As such, clinical skills alone are
      often insufficient to detect it and we describe psychometric tests such as
      symptom validity tests and relevant nonmedical investigations. Finally, we
      describe those areas of neurologic practice where symptom exaggeration and
      deception are more likely to occur, e.g., postconcussional syndrome, psychogenic
      nonepileptic seizures, motor weakness and movement disorders, and chronic pain.
      Factitious disorders are rare in clinical practice and their detection depends
      largely on the level of clinical suspicion supported by the systematic collection
      of relevant information from a variety of sources. In this chapter we challenge
      the accepted DSM-5 definition of factitious disorder and suggest that the
      traditional glossaries have neglected the extent to which a person's reported
      symptoms can be considered a product of intentional choice or selective
      psychopathology largely beyond the subject's voluntary control, or more likely,
      both. We present evidence to suggest that neurologists preferentially diagnose
      factitious presentations in healthcare workers as "hysterical," possibly to avoid
      the stigma of simulated illness.

PMID- 27719869
TI  - Prognosis of functional neurologic disorders.
AB  - The prognosis of functional (psychogenic) neurologic disorders is important in
      being able to help answer patients' and carers' questions, determine whether
      treatment is worthwhile, and to find out which factors predict outcome. We
      reviewed data on prognosis of functional neurologic disorders from two systematic
      reviews on functional motor disorders and dissociative (nonepileptic) seizures as
      well as additional studies on functional visual and sensory symptoms.
      Methodologic problems include heterogeneity in studied samples and outcome
      measures, diagnostic suspicion and referral bias, small size and retrospective
      design of available studies, possible treatments during follow-up, and literature
      review bias. With these caveats, the prognosis of functional neurologic disorders
      does appear to be generally unfavorable. In most studies, functional motor
      symptoms and psychogenic nonepileptic attacks remain the same or are worse in the
      majority of patients at follow-up. Measures of quality of life and working status
      were often poor at follow-up. Frequency of misdiagnosis at follow-up was as low
      as other neurologic and psychiatric disorders. Long duration of symptoms was the
      most distinct negative predictor. Early diagnosis and young age seem to predict
      good outcome. Emotional disorders and personality disorders were inconsistent
      predictors. Litigation and state benefits were found to be negative predictors in
      some studies, but others found they did not influence outcome.

PMID- 27719870
TI  - Explanation as treatment for functional neurologic disorders.
AB  - There is widespread agreement that the way health professionals communicate the
      diagnosis of functional neurologic disorders (FND) has a central role in
      treatment, as it does arguably for most conditions. In this chapter we discuss
      barriers to effective diagnosis, different models of explanation and evidence
      regarding the importance of effective communication of the diagnosis in FND,
      especially movement disorders, and dissociative (nonepileptic) seizures. Debates
      and disagreements about how to go about this task often reflect different
      theoretic models held by health professionals rather than evidence. More evidence
      is required to know whether an initial emphasis on one model is more or less
      effective than another (e.g., a functional model vs. a psychologic model). We
      conclude, however, that there are a number of generic components to effective
      explanation shared by most authors on the topic that form the basis of a
      consensus. These include taking the patient seriously, giving the problem a
      diagnostic label, explaining the rationale for the diagnosis, some discussion of
      how the symptoms arise, emphasis on the potential for reversibility (rather than
      damage), and effective triage and referral for other treatment where appropriate.
      Although explanation can sometimes be therapeutic on its own, its role is
      probably more important as a facilitator to other therapy, including self-help,
      physical treatments, and psychotherapy.

PMID- 27719871
TI  - Physical treatment of functional neurologic disorders.
AB  - Physical interventions are widely considered an important part of treatment of
      functional neurologic disorders (FNDs). The evidence base for physical
      interventions has been limited to a collection of case series, but the recent
      publication of several large cohort studies and a randomized controlled trial
      have provided stronger evidence to support its use. While the evidence for
      efficacy appears to be promising, details on how this should be delivered remain
      limited, perhaps due to the dominance of psychologically focused etiologic
      models. A move towards understanding how the symptoms of FND are generated on a
      neurobiologic level has resulted in an expansion of pathophysiologic models
      providing a clearer rationale for physical treatment. In this context, the motor
      symptoms of FND can be considered as learnt patterns of movement, driven by
      attention and belief. Physical treatment aims to retrain movement by redirecting
      attention and addressing unhelpful illness beliefs and behaviors. The patient's
      problems should be considered in a broad biopsychosocial framework where symptom
      predisposing, precipitating, and perpetuating factors can be addressed within a
      multidisciplinary environment as a gold standard. Further research is required to
      refine interventions and create evidence-based treatment guidelines.

PMID- 27719872
TI  - Psychologic treatment of functional neurologic disorders.
AB  - The management of patients with functional neurologic disorders poses many
      challenges. Psychologic treatments may well start at the point of delivery of the
      diagnosis, when careful explanations about the nature of the disorder have to be
      given to the patient and possibly also relatives/carers. Different conceptual
      models may assist in explaining the factors underlying the presentation, two of
      which (functional and dissociative) are briefly outlined here. The challenges for
      neurologists and psychiatrists of delivering a psychologic formulation as part of
      the diagnosis delivery are considered, along with the importance of clear
      communication between professionals involved in the patient's care. Existing
      literature on treatments incorporating psychologic components suggests that,
      despite limitations in the study designs and the potential bias in some outcome
      evaluations, there is evidence to support the use of psychologic interventions
      for at least some functional neurologic disorders, although larger and better
      designed studies are required in this area.

PMID- 27719873
TI  - Hypnosis as therapy for functional neurologic disorders.
AB  - Suggestion in hypnosis has been applied to the treatment of functional neurologic
      symptoms since the earliest descriptions of hypnosis in the 19th century.
      Suggestion in this sense refers to an intentional communication of beliefs or
      ideas, whether verbally or nonverbally, to produce subjectively convincing
      changes in experience and behavior. The recognition of suggestion as a
      psychologic process with therapeutic applications was closely linked to the
      derivation of hypnosis from earlier healing practices. Animal magnetism, the
      immediate precursor of hypnosis, arrived at a psychologic concept of suggestion
      along with other ideas and practices which were then incorporated into hypnosis.
      Before then, other forms of magnetism and ritual healing practices such as
      exorcism involved unintentionally suggestive verbal and nonverbal stimuli. We
      consider the derivation of hypnosis from these practices not only to illustrate
      the range of suggestive processes, but also the consistency with which suggestion
      has been applied to the production and removal of dissociative and functional
      neurologic symptoms over many centuries. Nineteenth-century practitioners treated
      functional symptoms with induction of hypnosis per se; imperative suggestions, or
      commands for specific effects; "medical clairvoyance" in hypnotic trance, in
      which patients diagnosed their own condition and predicted the time and manner of
      their recovery; and suggestion without prior hypnosis, known as "fascination" or
      "psychotherapeutics." Modern treatments largely involve different types of
      imperative suggestion with or without hypnosis. However, the therapeutic
      application of suggestion in hypnosis to functional and other symptoms waned in
      the first half of the 20th century under the separate pressures of behaviorism
      and psychoanalysis. In recent decades suggestion in hypnosis has been more widely
      applied to treating functional neurologic symptoms. Suggestion is typically
      applied within the context of other treatment approaches, such as cognitive
      behavioral, rehabilitative, or psychodynamic therapy. Suggestions are generally
      symptom-focused (designed to resolve a symptom) or exploratory (using methods
      such as revivification or age regression to explore experiences associated with
      symptom onset). The evidence base is dominated by case studies and series, with a
      paucity of randomized controlled trials. Future evaluation studies should allow
      for the fact that suggestion with or without hypnosis is a component of broader
      treatment interventions adapted to a wide range of symptoms and presentations. An
      important role of the concept of suggestion in the management of functional
      neurologic symptoms is to raise awareness of how interactions with clinicians and
      wider clinical contexts can alter expectancies and beliefs of patients in ways
      that influence the onset, course, and remission of symptoms.

PMID- 27719874
TI  - Nature of the placebo and nocebo effect in relation to functional neurologic
      disorders.
AB  - Placebos have long been considered a nuisance in clinical research, for they have
      always been used as comparators for the validation of new treatments. By
      contrast, today they represent an active field of research, and, due to the
      involvement of many mechanisms, the study of the placebo effect can actually be
      viewed as a melting pot of concepts and ideas for neuroscience. There is not a
      single placebo effect, but many, with different mechanisms across different
      medical conditions and therapeutic interventions. Expectation, anxiety, and
      reward are all involved, as well as a variety of learning phenomena and genetic
      variants. The most productive models to better understand the neurobiology of the
      placebo effect are pain and Parkinson's disease. In these medical conditions,
      several neurotransmitters have been identified, such as endogenous opioids,
      cholecystokinin, dopamine, as well as lipidic mediators, for example,
      endocannabinoids and prostaglandins. Since the placebo effect is basically a
      psychosocial context effect, these data indicate that different social stimuli,
      such as words and therapeutic rituals, may change the chemistry of the patient's
      brain, and these effects are similar to those induced by drugs.

PMID- 27719875
TI  - The role of placebo in the diagnosis and treatment of functional neurologic
      disorders.
AB  - Placebo therapy can produce meaningful, clinical relief for a variety of
      conditions. While placebos are not without their ethically fraught history, they
      continue to be used, largely covertly, even today. Because the prognosis for
      psychogenic disorders is often poor and recovery may be highly dependent on the
      patient's belief in the diagnosis and treatment regimen, some physicians find
      placebo therapy for psychogenic disorders compelling, but also particularly
      contentious. Yet placebos also have a long tradition of being used for
      provocative diagnosis (wherein placebo is used to elicit and/or terminate the
      symptoms as a way of diagnosing symptoms as "psychogenic"). In this chapter we
      discuss cases describing placebo as therapy for psychogenic disorders and the
      challenges related to embedded Cartesian beliefs in Western medicine. The
      legitimate ethical reservations against placebo therapy, in general, have been
      related to assumptions about their "inertness" and a requirement for deception,
      both which are being refuted by emerging data. In this chapter, we also re
      evaluate the concerns associated with placebo therapy for psychogenic disorders
      by asking, "Are we harming patients by withholding placebo treatment?"

PMID- 27719876
TI  - Neurophysiologic studies of functional neurologic disorders.
AB  - Functional neurologic disorders are largely genuine and represent conversion
      disorders, where the dysfunction is unconscious, but there are some that are
      factitious, where the abnormality is feigned and conscious. Malingering, which
      can have the same manifestations, is similarly feigned, but not considered a
      genuine disease. There are no good methods for differentiating these three
      entities at the present time. Physiologic studies of functional weakness and
      sensory loss reveal normal functioning of primary motor and sensory cortex, but
      abnormalities of premotor cortex and association cortices. This suggests a top
      down influence creating the dysfunction. Studies of functional tremor and
      myoclonus show that these disorders utilize normal voluntary motor structures to
      produce the involuntary movements, again suggesting a higher-level abnormality.
      Agency is abnormal and studies shows that dysfunction of the temporoparietal
      junction may be a correlate. The limbic system is overactive and might initiate
      involuntary movements, but the mechanism for this is not known. The limbic system
      would then be the source of top-down dysfunction. It can be speculated that the
      involuntary movements are involuntary due to lack of proper feedforward
      signaling.

PMID- 27719877
TI  - Transcranial magnetic stimulation and sedation as treatment for functional
      neurologic disorders.
AB  - Functional neurologic disorder (FND), also known as conversion disorder, is
      common and often associated with a poor prognosis. It has been relatively
      neglected by research and as such there is a conspicuous lack of evidence-based
      treatments. Physical and psychologic therapies are the main treatment modalities,
      over and above reassurance and sensitive explanation of the diagnosis. However
      there are two other historic treatments that have seen a recent resurgence of
      interest and use. The first is electric stimulation, which was initially
      pioneered with direct stimulation of nerves but now used indirectly (and
      therefore noninvasively) in the form of transcranial magnetic stimulation (TMS).
      The second is (therapeutic) sedation, previously known as "abreaction," where it
      was mostly used in the context of psychologic investigation and treatment, but
      now increasingly advocated during rehabilitation as a way to therapeutically
      demonstrate reversibility of symptoms. This chapter introduces the background of
      these treatment modalities, their evolution into their current applications
      before critically evaluating their current evidence base and exploring possible
      mechanisms of action. It also tentatively suggests when they should be considered
      in current practice and briefly considers their future potential. In summary
      there is encouraging preliminary evidence to suggest that both TMS and sedation
      may be effective treatments for FNDs.

PMID- 27719878
TI  - Inpatient treatment for functional neurologic disorders.
AB  - Patients with functional neurologic disorders present to clinicians with a
      variety of symptomatic manifestations, with various levels of severity,
      chronicity, and comorbidity, as well as with various degrees of past adversity,
      intrinsic resilience, and available external support. Clearly, treatment must be
      individualized. For those patients who have been severely or chronically
      impaired, especially if adequate prior outpatient treatments have failed,
      inpatient treatment that integrates the various modalities outlined here provides
      a rational route of rescue from a course otherwise potentially characterized by
      protracted dependence and disability. Based on the data currently available, we
      believe this treatment approach is worthy of further study to refine the
      component treatment strategies and enhance the potentially most effective
      ingredients. For patients with severe levels of disability, who could be managed
      in a multimodal day-treatment program, that approach also warrants further
      consideration.

PMID- 27719879
TI  - Imaging studies of functional neurologic disorders.
AB  - Brain imaging techniques provide unprecedented opportunities to study the neural
      mechanisms underlying functional neurologic disorder (FND, or conversion
      disorder), which have long remained a mystery and clinical challenge for
      physicians, as they arise with no apparent underlying organic disease. One of the
      first questions addressed by imaging studies concerned whether motor conversion
      deficits (e.g., hysteric paralysis) represent a form of (perhaps unconscious)
      simulation, a mere absence of voluntary movement, or more specific disturbances
      in motor control (such as abnormal inhibition). Converging evidence from several
      studies using different techniques and paradigms has now demonstrated distinctive
      brain activation patterns associated with functional deficits, unlike those seen
      in actors simulating similar deficits. Thus, patients with motor FND show
      consistent hypoactivation of both cortical and subcortical motor pathways, with
      frequent increases in other brain areas within the limbic system, but no
      recruitment of prefrontal regions usually associated with voluntary motor
      inhibition. Other studies point to a dysfunction in sensorimotor integration and
      agency - related to parietal dysfunction - and abnormal motor planning related to
      supplementary motor area and prefrontal areas. These findings not only suggest
      that functional symptoms reflect a genuine brain dysfunction, but also give new
      insights into how they are produced. However, fewer studies attempted to
      understand why these symptoms are produced and linked to potential psychologic or
      emotional risk/triggering factors. Results from such studies point towards
      abnormal limbic regulation with heightened emotional arousal and amygdalar
      activity, potentially related to engagement of defense systems and stereotyped
      motor behaviors, mediated by medial prefrontal cortex and subcortical structures,
      including the periaqueductal gray area and basal ganglia. In addition, across
      different symptom domains, several studies reported abnormal recruitment of
      ventromedial prefrontal cortex (vmPFC), a region known to regulate emotion
      appraisal, memory retrieval, and self-reflective representations. The vmPFC might
      provide important modulatory signals to both cortical and subcortical
      sensorimotor, visual, and even memory circuits, promoting maladaptive self
      protective behaviors based on personal affective appraisals of particular events.
      A better understanding of such a role of vmPFC in FND may help link how and why
      these symptoms are produced. Further research is also needed to determine brain
      activation patterns associated with FND across different types of deficits and
      different evolution stages (e.g., acute vs. chronic vs. recovered).

PMID- 27719880
TI  - Dissociation and functional neurologic disorders.
AB  - Dissociation has been cited as a possible psychologic mechanism underpinning
      functional neurologic disorders (FND) since the 19th century. Since that time,
      changes in psychiatric classification have created confusion about what the term
      dissociation actually means. The available evidence suggests that it now refers
      to at least two qualitatively distinct types of phenomena: detachment (an altered
      state of consciousness characterized by a sense of separation from the self or
      world) and compartmentalization (a reversible loss of voluntary control over
      apparently intact processes and functions), as well as their underlying
      mechanisms. This chapter considers some of the problems with conflating these
      phenomena under a single heading as well as the relationship between detachment,
      compartmentalization, and FND. It is argued that FNDs are fundamentally
      compartmentalization disorders, but that detachment is often part of the clinical
      picture and may contribute to the development and maintenance of functional
      symptoms in many cases. By this view, understanding compartmentalization requires
      an appreciation of the mechanisms involved in controlling and accessing mental
      processes and contents. Two possible mechanisms in this regard are described and
      the evidence for these is considered, followed by a discussion of clinical and
      empiric implications.

PMID- 27719881
TI  - Hypnosis as a model of functional neurologic disorders.
AB  - In the 19th century it was recognized that neurologic symptoms could be caused by
      "morbid ideation" as well as organic lesions. The subsequent observation that
      hysteric (now called "functional") symptoms could be produced and removed by
      hypnotic suggestion led Charcot to hypothesize that suggestion mediated the
      effects of ideas on hysteric symptoms through as yet unknown effects on brain
      activity. The advent of neuroimaging 100 years later revealed strikingly similar
      neural correlates in experiments matching functional symptoms with clinical
      analogs created by suggestion. Integrative models of suggested and functional
      symptoms regard these alterations in brain function as the endpoint of a broader
      set of changes in information processing due to suggestion. These accounts
      consider that suggestions alter experience by mobilizing representations from
      memory systems, and altering causal attributions, during preconscious processing
      which alters the content of what is provided to our highly edited subjective
      version of the world. Hypnosis as a model for functional symptoms draws attention
      to how radical alterations in experience and behavior can conform to the content
      of mental representations through effects on cognition and brain function.
      Experimental study of functional symptoms and their suggested counterparts in
      hypnosis reveals the distinct and shared processes through which this can occur.

PMID- 27719882
TI  - Preface.

PMID- 27719883
TI  - Foreword.

PMID- 27719884
TI  - Effect of molecular weight on the transepithelial transport and peptidase
      degradation of casein-derived peptides by using Caco-2 cell model.
AB  - The transepithelial transport routes of casein-derived peptides with different
      molecular weights (MWs) were investigated using a Caco-2 cell monolayer. The
      peptidase hydrolysis during transport was also studied. The results indicate that
      the paracellular route was the main pathway for F1 (1600-1300Da) and F2 (1000
      500Da), and the bioavailabilities were 10.66% and 9.54%, respectively. Peptidase
      hydrolysis results reveal that brush-border peptidases (BBPs) as well as some
      other peptidases were responsible for peptide degradation in the paracellular
      route. The maximum hydrolysis rate of the former was 6.91 and 5.59MUM Gly/min for
      the latter. However, PepT1 was involved in the transport of F3 (<500Da) and its
      bioavailability was 16.23%. BBPs were the main peptidases involved in the PepT1
      transport and the maximum hydrolysis rate was 11.4MUM Gly/min. Furthermore, we
      found that the amino acid sequence of di- and tripeptides might affect their
      bioavailabilities significantly.

PMID- 27719885
TI  - Contribution of individual phenolics to antioxidant activity and in vitro
      digestibility of wild rices (Zizania aquatica L.).
AB  - Zizania aquatica L. was analysed for total flavonoids, phenolics and HPLC profile
      in both free and bound phenolic fractions. The highest content of flavonoids (378
      455mgRE/kg) was detected in bound fractions, while the highest polyphenols
      content (1061-2988mgGAE/kg) was determined in free fractions. Additionally,
      predominant phenolics were identified. To understand the contribution of
      individual phenolics to an antioxidant activity their mutual correlations were
      evaluated. Regarding free flavonoids, the main contributors to an antioxidant
      activity (r>0.7111) were epigallocatechin, epicatechin and rutin; while
      epicatechin, quercetin and rutin were the main contributors in bound fractions
      (r>0.6868). Concerning free phenolic acids, the main contributors to an
      antioxidant activity (r>0.7585) were ferulic, vanillic, ellagic, sinapic and
      syringic acids; while caffeic, sinapic, syringic, o-coumaric, p-hydroxy benzoic,
      vanillic, protocatechuic, gallic and cinnamic acids were the main contributors in
      bound fractions of wild rice (r>0.6538). Finally, in vitro organic matter and dry
      matter digestibility were assessed.

PMID- 27719886
TI  - Preparation and properties of octenyl succinate beta-cyclodextrin and its
      application as an emulsion stabilizer.
AB  - The aim of this study was to synthesize and characterize the octenyl succinic
      beta-cyclodextrin (OS-beta-CD) and assess its application as a potential emulsion
      stabilizer. OS-beta-CD was prepared by esterifying beta-CD with OSA under
      alkaline conditions. The properties of OS-beta-CD were characterized by Fourier
      transform infrared, 13C and 1H NMR spectroscopy, X-ray diffraction (XRD), which
      demonstrated that OS groups had been introduced into the beta-CD molecules and
      most of OS substitution occurred at the C-6 hydroxyl group of glycosyl units. The
      properties of emulsions stabilized by beta-CD and OS-beta-CD were evaluated via
      surface and interface tensiometry, determination of the creaming index and
      droplet size. The results showed that emulsions stabilized by beta-CD broke just
      after 24h storage at 25 degrees C. The emulsions prepared by OS-beta-CD with all
      degree of substitution (DS) possessed a smaller oil droplet size and improved
      storage stability compared with that of the emulsion generated using beta-CD.

PMID- 27719887
TI  - Intelligent pH indicator film composed of agar/potato starch and anthocyanin
      extracts from purple sweet potato.
AB  - A new colorimetric pH indicator film was developed using agar, potato starch, and
      natural dyes extracted from purple sweet potato, Ipomoea batatas. Both agar and
      potato starch are solid matrices used to immobilize natural dyes, anthocyanins.
      The ultraviolet-visible (UV-vis) spectrum of anthocyanin extract solutions and
      agar/potato starch films with anthocyanins showed color variations to different
      pH values (pH 2.0-10.0). Fourier transform infrared (FT-IR) and UV-vis region
      spectra showed compatibility between agar, starch, and anthocyanin extracts.
      Color variations of pH indicator films were measured by a colorimeter after
      immersion in different pH buffers. An application test was conducted for
      potential use as a meat spoilage sensor. The pH indicator films showed pH changes
      and spoilage point of pork samples, changing from red to green. Therefore, the
      developed pH indicator films could be used as a diagnostic tool for the detection
      of food spoilage.

PMID- 27719888
TI  - Impact of salt reduction on biogenic amines, fatty acids, microbiota, texture and
      sensory profile in traditional blood dry-cured sausages.
AB  - Meat industry needs to reduce salt in their products due to health issues. The
      present study evaluated the effect of salt reduction from 6% to 3% in two
      Portuguese traditional blood dry-cured sausages. Physicochemical and
      microbiological parameters, biogenic amines, fatty acids and texture profiles and
      sensory panel evaluations were considered. Differences due to salt reduction were
      perceptible in a faint decline of water activity, which slightly favoured
      microbial growth. Total biogenic amines content ranged from 88.86 to 796.68mgkg-1
      fresh matter, with higher amounts, particularly of cadaverine, histamine and
      tyramine, in low-salt products. Still, histamine and other vasoactive amines
      remained at low levels, thus not affecting consumers' health. Regarding fatty
      acids, no significant differences were observed due to salt. However, texture
      profile analysis revealed lower resilience and cohesiveness in low-salt products,
      although no textural changes were observed by the sensory panel. Nevertheless,
      low-salt sausages were clearly preferred by panellists.

PMID- 27719889
TI  - Influence of non-starchy polysaccharides on barley milling behavior and
      evaluating bioactive composition of milled fractions.
AB  - Hulless barley cultivars grown at various altitudes were subjected to different
      conditioning treatments prior to roller milling. Amongst all treatments,
      conditioning grains to a moisture content of 14% for 30min was found to be
      optimum. The bran fractions displayed greater levels of non-starchy
      polysaccharides and bioactive components as compared to refined flour fraction.
      The presence of greater levels of beta-glucan in whole barley flour and bran of
      high altitude cultivars affected the refined flour yield inversely. Cultivars
      having higher total and insoluble arabinoxylans also resulted in lower flour
      yields (R=-0.76; R=-0.73). The damaged starch content of barley cultivars ranged
      between 5.1% and 8.7% which correlated positively with the content of beta
      glucans (up to R=0.77) and arabinoxylans (up to R=0.80) in bran and refined flour
      fractions. The anthocyanin and total phenolic contents of refined flours ranged
      between 3.9-7.6MUg/g and 1299-1607MUg FAE/g and was higher for high altitude
      cultivars.

PMID- 27719890
TI  - Free radical scavenging potency of quercetin catecholic colonic metabolites:
      Thermodynamics of 2H+/2e- processes.
AB  - Reaction energetics of the double (2H+/2e-), i.e., the first 1H+/1e- (catechol->
      phenoxyl radical) and the second 1H+/1e- (phenoxyl radical-> quinone) free
      radical scavenging mechanisms of quercetin and its six colonic catecholic
      metabolites (caffeic acid, hydrocaffeic acid, homoprotocatechuic acid,
      protocatechuic acid, 4-methylcatechol, and catechol) were computationally studied
      using density functional theory, with the aim to estimate the antiradical potency
      of these molecules. We found that second hydrogen atom transfer (HAT) and second
      sequential proton loss electron transfer (SPLET) mechanisms are less energy
      demanding than the first ones indicating 2H+/2e- processes as inherent to
      catechol moiety. The Gibbs free energy change for reactions of inactivation of
      selected free radicals indicate that catecholic colonic metabolites constitute an
      efficient group of more potent scavengers than quercetin itself, able to
      deactivate various free radicals, under different biological conditions. They
      could be responsible for the health benefits associated with regular intake of
      flavonoid-rich diet.

PMID- 27719891
TI  - Flavonoid composition of orange peel and its association with antioxidant and
      anti-inflammatory activities.
AB  - Dried citrus peel derived from Citrus reticulata, also called "chenpi", possesses
      a complex mixture of flavonoids and has a history of traditional use to treat a
      variety of digestive disorders. We compared three sources of conventional chenpi
      from California (USA), Guangxi, Zhejiang, and two sources of "nchenpi", which
      contain greater nobiletin content, from Sichuan and Xinhui (China). Xinhui orange
      peel extract (OPE) had highest content of polymethoxylated flavones, along with
      greatest capacity to scavenge 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic
      acid) (ABTS), 2,2-diphenyl-1-pcrylhydrazyl (DPPH), and 2,2'-azobis-2-methyl
      propanimidamide, dihydrochloride (AAPH) radicals and nitric oxide (NO). OPE also
      had higher NO, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2)
      inhibitory activity than an equivalent mixture of flavonoids (P<0.05). In
      conclusion, nobiletin is a good chemical marker for assessing the anti
      inflammatory potential of OPE from different sources. Obtaining "nchenpi" from
      either Sichuan or Xinhui provided potentially superior health benefits compared
      to conventional chenpi sources.

PMID- 27719892
TI  - Subcritical ethanol extraction of flavonoids from Moringa oleifera leaf and
      evaluation of antioxidant activity.
AB  - A large-scale process to extract flavonoids from Moringa oleifera leaf by
      subcritical ethanol was developed and HPLC-MS analysis was conducted to
      qualitatively identify the compounds in the extracts. To optimize the effects of
      process parameters on the yield of flavonoids, a Box-Behnken design combined with
      response surface methodology was conducted in the present work. The results
      indicated that the highest extraction yield of flavonoids by subcritical ethanol
      extraction could reach 2.60% using 70% ethanol at 126.6 degrees C for 2.05h
      extraction. Under the optimized conditions, flavonoids yield was substantially
      improved by 26.7% compared with the traditional ethanol reflux method while the
      extraction time was only 2h, and obvious energy saving was observed. FRAP and
      DPPH assays showed that the extracts had strong antioxidant and free radical
      scavenging activities.

PMID- 27719893
TI  - Lipid composition and emulsifying properties of canola lecithin from enzymatic
      degumming.
AB  - This study investigated the polar lipid composition and emulsifying properties of
      canola lecithin from enzymatic degumming (CLED). Phospholipase A1 was used for
      enzymatic degumming of crude canola oil to collect lecithin sample. Canola
      lecithin from water degumming (CLWD) was also collected and served as the
      control. The results showed that the contents of phosphatidylethanolamine (PE)
      (2.99%) and phosphatidylcholine (PC) (6.59%) in CLED were significantly lower
      than that in CLWD (PE 15.55% and PC 21.93%); while the content of
      lysophosphatidylcholine (LPC) (19.45%) in CLED was significantly higher than that
      in CLWD (3.27%). Unsaturated fatty acids accounted for a higher percentage of the
      total fatty acids in CLED than in CLWD. CLED promoted more stable o/w emulsions
      than CLWD. This study provides a better understanding of the chemical nature of
      CLED, and important information for utilization of CLED as o/w emulsifier.

PMID- 27719894
TI  - Effects of ultrasound pre-treatment on the structure of beta-conglycinin and
      glycinin and the antioxidant activity of their hydrolysates.
AB  - The effect of power, time and temperature of ultrasound on the structure of beta
      conglycinin (7S) and glycinin (11S), and on the antioxidant activity of their
      hydrolysates were investigated. All ultrasound treated 7S and 11S fractions
      showed an increase in the alpha-helix and beta-turn proportions, and a decrease
      in beta-sheet and random coil proportions. The polarity of 7S and 11S
      microenvironment increased after ultrasound treatment. Ultrasound treatment
      significantly increased the reduction capacity and iron chelating capacity of 7S
      and 11S hydrolysates. The degree of hydrolysis and free SH groups of 7S and 11S
      hydrolysates increased after ultrasound pre-treatment. The relative content of
      high molecular weight peptides reduced, and the relative content of low molecular
      weight peptides increased in ultrasound treated 7S and 11S hydrolysates. The
      ultrasonication exposed certain groups of 7S and 11S fractions, improved contact
      with enzymes, and increased the content of highly active soybean antioxidant
      peptides.

PMID- 27719895
TI  - Simultaneous determination of atropine and scopolamine in buckwheat and related
      products using modified QuEChERS and liquid chromatography tandem mass
      spectrometry.
AB  - A method was developed for the determination of atropine and scopolamine in
      buckwheat and related products. A modified QuEChERS (Quick, Easy, Cheap,
      Effective, Rugged and Safe) extraction procedure was evaluated. Dispersive solid
      phase extraction (d-SPE) was studied as clean-up step, using graphitized black
      carbon (GBC) and primary secondary amine (PSA). The extract was diluted with
      water (50:50, v/v) prior to chromatographic analysis. The method was validated
      and recoveries (except chia samples spiked at 10MUg/kg) ranged from 75% to 92%.
      Intra and inter-day precision was lower than or equal to 17%. The limit of
      quantification of atropine and scopolamine was 0.4 and 2MUg/kg, respectively.
      Eight types of samples (buckwheat, wheat, soy, buckwheat flour, buckwheat noodle,
      amaranth grain, chia seeds and peeled millet) were analyzed. Target compounds
      were not found above the detection limits of the method, but three transformation
      products of scopolamine (norscopine, hydroscopolamine and dihydroxyscopolamine)
      were putative identified in the tested samples using high resolution mass
      spectrometry (Exactive-Orbitrap).

PMID- 27719897
TI  - Determination of eight pesticides in Lycium barbarum by LC-MS/MS and dietary risk
      assessment.
AB  - A LC-MS/MS method for determination of eight pesticides (triadimefon,
      sulfoxaflor, flusilazole, tebuconazole, difenoconazole, amitraz, azoxystrobin,
      and thiophanate-methyl) in Lycium barbarum was established. The samples were
      extracted with acetonitrile, and then cleaned up by primary secondary amine. The
      extracts were diluted with 0.1% formic acid in water. The results showed that at
      the fortified levels of 0.01-10mg/kg, the average recoveries of these pesticides
      ranged from 82.1% to 96.2% with the relative standard deviations lower than 7%.
      The half-lives of eight pesticides were 1.3-5.0days in Lycium barbarum fruits.
      The pre-harvest interval of all pesticides mentioned above were investigated.
      Tebuconazole (14days), sulfoxaflor (14days) and flusilazole (28days) have longer
      pre-harvest interval than the others which have 7days. The dietary risks,
      assessed as hazard quotients, were far below 100%. The results showed that the
      eight pesticides applied to Lycium barbarum were comparably safe for the
      consumer.

PMID- 27719896
TI  - Analysis of seven salad rocket (Eruca sativa) accessions: The relationships
      between sensory attributes and volatile and non-volatile compounds.
AB  - Sensory and chemical analyses were performed on accessions of rocket (Eruca
      sativa) to determine phytochemical influences on sensory attributes. A trained
      panel was used to evaluate leaves, and chemical data were obtained for polyatomic
      ions, amino acids, sugars and organic acids. These chemical data (and data of
      glucosinolates, flavonols and headspace volatiles previously reported) were used
      in Principal Component Analysis (PCA) to determine variables statistically
      important to sensory traits. Significant differences were observed between
      samples for polyatomic ion and amino acid concentrations. PCA revealed strong,
      positive correlations between glucosinolates, isothiocyanates and sulfur
      compounds with bitterness, mustard, peppery, warming and initial heat mouthfeel
      traits. The ratio between glucosinolates and sugars inferred reduced perception
      of bitter aftereffects. We highlight the diversity of E. sativa accessions from a
      sensory and phytochemical standpoint, and the potential for breeders to create
      varieties that are nutritionally and sensorially superior to existing ones.

PMID- 27719898
TI  - Crystallization and melting properties of mixtures of milk fat stearin and omega
      3 rich oils.
AB  - Solid milk fat stearin (S25) can be a promising oxidation retarder due to its
      capacity to entrap liquid oils, especially for incorporating omega-3 (omega-3)
      rich oils into dairy products. Thermal properties of S25/omega-3 rich oil
      mixtures are necessary for such application. The effects of S25 on the
      crystallization and melting behaviours of omega-3 rich oils, namely fish oil
      (FO), linseed oil (LO) and krill oil (KO), were investigated by differential
      scanning calorimetry (DSC). Thermograms showed that with S25 concentration
      increasing, transitions of FO and LO shifted to lower and largely to higher
      temperatures, respectively, while crystallization temperature of KO slightly
      decreased. Negative, positive and low values of interaction enthalpy (DeltaHint)
      suggested the adverse, beneficial and limited effect of S25 on the
      crystallization of S25/FO, S25/LO and S25/KO mixtures, respectively. LO could
      have the best oxidative stability upon the addition of S25 since their
      interactions facilitated earlier and stronger crystallization.

PMID- 27719899
TI  - Alkali solution extraction of rice residue protein isolates: Influence of alkali
      concentration on protein functional, structural properties and lysinoalanine
      formation.
AB  - This study evaluated the nutrient property and safety of the rice residue protein
      isolates (RRPI) product (extracted by different alkali concentrations) by
      exploring the protein functional, structural properties and lysinoalanine (LAL)
      formation. The results showed that with the rising of alkali concentration from
      0.03M to 0.15M, the solubility, emulsifying and foaming properties of RRPI
      increased at first and then descended. When the alkali concentration was greater
      than 0.03M, the RRPI surface hydrophobicity decreased and the content of thiol
      and disulfide bond, Lys and Cys significantly reduced. By the analysis of HPLC,
      the content of LAL rose up from 276.08 to 15,198.07mg/kg and decreased to
      1340.98mg/kg crude protein when the alkali concentration increased from 0.03 to
      0.09M and until to 0.15M. These results indicated that RRPI alkaline extraction
      concentration above 0.03M may cause severe nutrient or safety problems of
      protein.

PMID- 27719900
TI  - Characterization of polyphenol oxidase from blueberry (Vaccinium corymbosum L.).
AB  - Polyphenol oxidase (PPO) was extracted and characterized from high-bush
      blueberries. PPO showed an optimum activity at pH 6.1-6.3 and 35 degrees C, with
      the enzyme showing significant activity over a wide temperature range (25-60
      degrees C). Catechol was the most readily oxidized substrate followed by 4
      methylcatechol, DL-DOPA, and dopamine. Blueberry PPO showed a Km of 15mM and Vmax
      of 2.57 DeltaA420nm/min*10-1, determined with catechol. PPO was completely
      inactivated in 20min at 85 degrees C, however, after 30minat 75 degrees C it
      showed about 10% residual activity. Thermal treatment at 55 and 65 degrees C for
      30min resulted in the partial inactivation of PPO. Ascorbic acid, sodium
      diethyldithiocarbamic acid, L-cysteine, and sodium metabisulfite were effective
      inhibitors of PPO at 1.0mM. Benzoic acid and cinnamic acid series inhibitors
      showed relatively weak inhibition of PPO (21.8-27.6%), even at as high as 2.0mM
      concentration.

PMID- 27719901
TI  - Free fatty acids and their esters modulate isothermal crystallization of
      anhydrous milk fat.
AB  - The effect of free fatty acids with different chain lengths or unsaturation
      degree on anhydrous milk fat (AMF) crystallization was evaluated. The impact of
      esterification was also studied using three triglycerides. Melted blends
      containing the additives at concentrations lower than 12wt.% were quenched at 25
      degrees C and isothermal crystallization was monitored by pulsed low-resolution
      nuclear magnetic resonance. In parallel, polarized light microscopy was used to
      observe the microstructure. Compounds based on long chain saturated fatty acids,
      i.e. palmitic, stearic, eicosanoic acids, tripalmitin and tristearin accelerated
      crystallization. Conversely, propanoic, hexanoic and oleic acids slowed down the
      process, while triacetin had no impact. Interestingly, above a critical
      concentration, the addition of palmitic, stearic or eicosanoic acids caused a
      transition from a one-step to two-step process. Gompertz model was used to fit
      the experimental data and to assess the influence of the molecular properties of
      the additives on the kinetic parameters.

PMID- 27719902
TI  - Gel characteristics and microstructure of fish myofibrillar protein/cassava
      starch composites.
AB  - The changes in fish myofibrillar protein/cassava starch composites in the starch
      fraction range from 0 to 1, with their total content maintained at 60mg/mL, were
      investigated in terms of textural properties, rheological behaviours, morphology,
      spatial distribution and protein molecular structure. The results revealed that
      the starch fraction of 0.5 was a critical point for the conversion of the protein
      matrix to starch matrix and conversion of the gel from elastic to weak. Moreover,
      the protein-starch synergistic effect on the storage modulus was strongest at
      fractions of 0.5 and 0.6, due to the formation of a semi-interpenetrating
      network, with more amylose from the melted starch granules interpenetrated with
      the protein molecules, and the absorption of water by the starch granules to
      concentrate the protein matrix. Additionally, no covalent interaction between the
      protein and starch occurred with increasing starch fraction, thus having no
      significant influence on the protein secondary structure.

PMID- 27719904
TI  - Nutritional and mineral contents of honey extracted by centrifugation and pressed
      processes.
AB  - In this study, wild honey samples extracted by two different methods
      (centrifugation and pressed processing) were characterized and compared based on
      their physicochemical, and nutritional properties, macro- and micro-mineral
      contents, and pollen counts. Twelve colonies of Africanized Apis mellifera were
      used; six honey samples were obtained by centrifugation and six by honeycomb
      press. All physicochemical parameters of honey samples (moisture, pH, total
      acidity, ash, dry matter, and qualitative absence of hydroxymethylfurfural) were
      within the limits established by EU legislation, and all parameters in pressed
      honey were superior (p<0.05). Nutritional contents (total carbohydrates, total
      lipids, total proteins, flavonoids, and ascorbic acid) and minerals (K, Ca, Mg,
      Na, Fe, Li, Zn) were also higher in pressed honey. The quantity of pollen in
      pressed honey samples was 5.6-fold higher than in centrifuged samples. Pressed
      honey, can be marked as a differentiated product with a higher mineral content
      and several nutritional properties.

PMID- 27719903
TI  - Qualitative and quantitative detection of honey adulterated with high-fructose
      corn syrup and maltose syrup by using near-infrared spectroscopy.
AB  - Near-infrared spectroscopy (NIR) was used for qualitative and quantitative
      detection of honey adulterated with high-fructose corn syrup (HFCS) or maltose
      syrup (MS). Competitive adaptive reweighted sampling (CARS) was employed to
      select key variables. Partial least squares linear discriminant analysis (PLS
      LDA) was adopted to classify the adulterated honey samples. The CARS-PLS-LDA
      models showed an accuracy of 86.3% (honey vs. adulterated honey with HFCS) and
      96.1% (honey vs. adulterated honey with MS), respectively. PLS regression (PLSR)
      was used to predict the extent of adulteration in the honeys. The results showed
      that NIR combined with PLSR could not be used to quantify adulteration with HFCS,
      but could be used to quantify adulteration with MS: coefficient (Rp2) and root
      mean square of prediction (RMSEP) were 0.901 and 4.041 for MS-adulterated samples
      from different floral origins, and 0.981 and 1.786 for MS-adulterated samples
      from the same floral origin (Brassica spp.), respectively.

PMID- 27719905
TI  - Improving the extraction of Ara h 6 (a peanut allergen) from a chocolate-based
      matrix for immunosensing detection: Influence of time, temperature and additives.
AB  - The extraction of Ara h 6 (a peanut allergen) from a complex chocolate-based food
      matrix was optimized by testing different temperatures, extraction times, and the
      influence of additives (NaCl and skimmed milk powder) in a total of 36 different
      conditions. Analyses were carried out using an electrochemical immunosensor.
      Three conditions were selected since they allowed the extraction of the highest
      levels of Ara h 6. These extractions were performed using 2g of sample and 20ml
      of Tris-HNO3 (pH=8) containing: a) 0.1M NaCl and 2g of skimmed milk powder at 21
      degrees C for 60min; b) 1M NaCl and 1g of skimmed milk powder at 21 degrees C for
      60min; and c) 2g of skimmed milk powder at 60 degrees C for 60min. Recoveries
      were similar or higher than 94.7%. This work highlights the importance to adjust
      extraction procedures regarding the target analyte and food matrix components.

PMID- 27719906
TI  - The dietary biogenic amines tyramine and histamine show synergistic toxicity
      towards intestinal cells in culture.
AB  - Tyramine and histamine are the biogenic amines (BA) most commonly found at high
      concentrations in food; they may even appear together at toxic concentrations.
      The present work examines, via real-time cell analysis, whether histamine and
      tyramine show synergistic toxicity towards intestinal cell cultures. Employing a
      constant equipotency ratio, their interaction was examined via the combination
      index (CI) method of Chou & Talalay. Co-treatment with tyramine and histamine was
      associated with a stronger cytotoxic effect than was treatment with either BA or
      on its own. Indeed, a synergistic interaction (CI<1) was observed in the range of
      concentrations found in foods. The results also show that histamine, at
      concentrations below the legal limit, increases the cytotoxicity of tyramine at
      concentrations frequently reached in some foods. The synergistic cytotoxicity of
      tyramine and histamine should be taken into account when establishing legal
      limits designed to ensure consumer safety.

PMID- 27719907
TI  - Compositional fingerprint of soy sauces via hydrophobic surface interaction.
AB  - In this work, the interaction of soy sauces with hydrophobic surfaces has been
      analyzed. Hydrophobic self-assembled monolayers on gold or silicon dioxide were
      used to harvest conditioning layers from soy sauce products with varying amounts
      of additives. The data was compared to adsorption of soy protein and glutamic
      acid as common ingredients. Spectral ellipsometry revealed that all tested sauces
      led to the formation of thin overlayers on hydrophobic surfaces. Products with
      less additives yielded adlayers in the same thickness range as pure soy protein.
      In contrast, sauces with more ingredients create distinctly thicker films. Using
      water contact angle goniometry, it is shown that all adlayers render the
      substrate more hydrophilic. Infrared spectroscopy provided a deeper insight into
      the adlayer chemistry and revealed that the adlayer composition is dominated by
      protein rich components. X-ray reflectivity on selected films provided further
      insight into the density profiles within the adlayers on the molecular scale.

PMID- 27719908
TI  - Effect of ultrasound followed by high pressure processing on prebiotic cranberry
      juice.
AB  - This work evaluated the effect of high pressure processing (HPP) and ultrasound
      (US) on the quality of prebiotic cranberry juice fortified with fructo
      oligosaccharides (FOS). The juice was subjected to HPP for 5min (450MPa) and to
      ultrasonic treatment for 5min (600 and 1200W/L) followed by HPP for 5min
      (450MPa). Chemical analyses were carried out to identify and quantify the
      anthocyanins, and to quantify FOS, organic acids, instrumental color, soluble
      solids, pH and antioxidant capacity. Both non-thermal treatments preserved the
      FOS content maintaining the prebiotic property of the juice. The retention of
      organic acids was high (>90%) and an increase in anthocyanin content (up to 24%)
      was observed when ultrasound was followed by HPP. The changes in instrumental
      color, soluble solids content and pH were negligible. The use of HPP and
      ultrasound processing has been proven satisfactory to treat prebiotic cranberry
      juice.

PMID- 27719909
TI  - Identification of the geographical origins of sea cucumber (Apostichopus
      japonicus) in northern China by using stable isotope ratios and fatty acid
      profiles.
AB  - Geographic traceability is an important issue for food quality and safety control
      of seafood. In this study,delta13C and delta15N values, as well as fatty acid
      (FA) content of 133 samples of A. japonicus from seven sampling points in
      northern China Sea were determined to evaluate their applicability in the origin
      traceability of A. japonicus. Principal component analysis (PCA) and discriminant
      analysis (DA) were applied to different data sets in order to evaluate their
      performance in terms of classification or predictive ability. delta13C and
      delta15N values could effectively discriminate between different origins of A.
      japonicus. Significant differences in the FA compositions showed the
      effectiveness of FA composition as a tool for distinguishing between different
      origins of A. japonicus. The two technologies, combined with multivariate
      statistical analysis, can be promising methods to discriminate A. japonicus from
      different geographical areas.

PMID- 27719910
TI  - Stability improvement of natural food colors: Impact of amino acid and peptide
      addition on anthocyanin stability in model beverages.
AB  - Anthocyanins are prone to chemical degradation and color fading in the presence
      of vitamin C. The potential of three amino acids (l-phenylalanine, l-tyrosine, l
      tryptophan) and a polypeptide (epsilon-poly-l-lysine) in prolonging the color
      stability of purple carrot anthocyanins (0.025%) in model beverages (0.05% l
      ascorbic acid, citric acid, pH 3.0) stored at elevated temperature (40 degrees
      C/7 days) was examined. In the absence of amino acids or peptides, anthocyanin
      degraded at first-order reaction rate. Addition of amino acids or peptide (0.1%)
      increased the color stability of anthocyanins, with the most significant
      improvement observed for l-tryptophan. The average half-life of anthocyanin color
      increased from 2 days to 6 days with l-tryptophan addition. Fluorescence
      quenching measurements revealed that the l-tryptophan interacted with
      anthocyanins mainly through hydrogen bonding, although some hydrophobic
      interaction may also have been involved. Overall, this study suggests that amino
      acid or peptide addition may prolong the color stability of anthocyanin in
      beverage products.

PMID- 27719911
TI  - iTRAQ analysis of low-phytate mung bean sprouts treated with sodium citrate,
      sodium acetate and sodium tartrate.
AB  - The effects of sodium citrate (SC), sodium acetate (SA) and sodium tartrate (ST)
      spraying on mung bean germination were investigated. Exogenous SC, ST and SA
      treatments significantly reduced the phytic acid content and increased the
      antioxidant enzyme activities. In this study, an iTRAQ-based proteomic approach
      was employed to explore the proteomes of mung bean sprouts, and 81, 101 and 90
      differentially expressed proteins were identified in 4-day-old SC-, SA- and ST
      treated mung bean sprouts, with 38 proteins present in all samples. Functional
      classification analysis showed that most of the differentially expressed proteins
      in mung bean sprouts subjected to the three treatments were involved in
      carbohydrate and energy metabolism. The inhibitory effect of the SA treatment was
      probably due to impairments in protein biosynthesis, whereas enhanced energy
      metabolism, accelerated reserve hydrolysis and protein processing were very
      important strategies for growth stimulation in response to ST and SC treatments.

PMID- 27719912
TI  - Nutrient compositions and antioxidant capacity of kiwifruit (Actinidia) and their
      relationship with flesh color and commercial value.
AB  - The nutritional quality and antioxidant capacity of China domestic kiwifruit and
      imported kiwifruit with different prices and the relationships of retail price
      among cultivars, nutritional qualities and flesh color were investigated. Results
      showed that cultivar was the main factor influencing nutritional quality, though
      the product region could also affect the cultivar characteristics to some extent.
      Additionally, nutritional quality and antioxidant capacity of kiwifruit had no
      relationship to the product region. What's more, there was no correlation among
      the nutrient compositions, antioxidant capacity and retail price of kiwifruit. At
      the same time, the flesh color was associated with greater commercial value but
      was not higher nutritional quality or antioxidant capacity. Thus indicates to
      consumers that imported kiwifruit were not all superior to local versions, and
      the priciest kiwifruit did not equal to the most nutritious kiwifruit, also the
      color kiwifruit. There still need more research to help consumers to choose
      kiwifruit.

PMID- 27719913
TI  - Investigation of caking by fat bridging in aged infant formula.
AB  - Three commercial infant formulas (denoted as P1, P2 and P3) were stored at 25, 45
      and 60 degrees C for up to 6weeks to study the caking phenomenon caused by fat
      bridging. At 60 degrees C, both the surface free-fat content and the caking
      strength increased significantly. Analysis of the fatty acid composition of P1
      showed that high-melting-point fatty acids were present on powder surface whereas
      low-melting-point fatty acids remained within powder particles. There was no
      preferential migration or retention of specific fatty acids in P2. The stearic
      acid content in the surface free-fat of P3 increased, largely due to a
      concentration gradient which contributed to the increased caking strength. The
      melting characteristics of surface free-fat analyzed by DSC were consistent with
      their fatty acid compositions analyzed by GC-MS/FID. Confocal laser scanning
      microscopy (CLSM) showed higher occurrence of large fat globules after 6weeks'
      storage.

PMID- 27719914
TI  - Physicochemical and antioxidant characterization of Justicia spicigera.
AB  - Extracts with water:ethanol (100:0, 70:30, 50:50, 30:70, 0:100) solutions from
      fresh (F), just dried (JD), dried and stored for one year (DS) Justicia spicigera
      leaves were obtained using the stirring and ultrasound techniques. Extracts were
      analyzed in physicochemical and antioxidant characteristics. Identification of
      chemical compounds by gas chromatography-mass spectroscopy (GC-MS) was also
      performed. 2.14+/-0.91, 5.67+/-1.70, and 8.52+/-4.97g Gallic acid
      equivalents/100g dry weight (d.w.) of phenolic compounds were found, in average,
      for F, JD, and DS J. spicigera, respectively. 2.22+/-1.31, 2.58+/-2.11, and
      8.48+/-3.78g Trolox equivalents/100g d.w. were detected with the ABTS method and
      0.49+/-0.33, 1.23+/-0.87, and 0.88+/-0.94g with the DPPH method for F, JD and DS
      J. spicigera, respectively. Eucalyptol, phytol, and azulene were identified as
      the main compounds. J. spicigera showed colors (green-iridescent, green-yellow,
      or pink of different intensities) and antioxidant characteristics depending on
      the solvent concentration. Extracts could be used in the food and pharmaceutical
      industries.

PMID- 27719915
TI  - Evaluation of selenium in dietary supplements using elemental speciation.
AB  - Selenium-enriched dietary supplements containing various selenium compounds are
      readily available to consumers. To ensure proper selenium intake and consumer
      confidence, these dietary supplements must be safe and have accurate label
      claims. Varying properties among selenium species requires information beyond
      total selenium concentration to fully evaluate health risk/benefits A LC-ICP-MS
      method was developed and multiple extraction methods were implemented for
      targeted analysis of common "seleno-amino acids" and related oxidation products,
      selenate, selenite, and other species relatable to the quality and/or accuracy of
      the labeled selenium ingredients. Ultimately, a heated water extraction was
      applied to recover selenium species from non-selenized yeast supplements in
      capsule, tablet, and liquid forms. For selenized yeast supplements, inorganic
      selenium was monitored as a means of assessing selenium yeast quality. A variety
      of commercially available selenium supplements were evaluated and discrepancies
      between labeled ingredients and detected species were noted.

PMID- 27719916
TI  - Proteomic analysis of anti-nutritional factors (ANF's) in soybean seeds as
      affected by environmental and genetic factors.
AB  - The genotype (G), environment (E), and the relationship between G and E on
      soybean seed anti-nutritional factors (ANF's) were examined under three different
      agro-climatic conditions. The field trials were conducted at Maryland, South
      Carolina and South Dakota using nine region specific genotypes. At each location,
      the nine genotypes were grown with two planting/sowing dates. Differentially
      expressed protein spots from the two-dimensional gel electrophoresis were
      analyzed using mass spectrometry. Seven ANF's corresponding to soybean agglutinin
      and Kunitz trypsin inhibitor were identified based on the statistical
      significance levels at p<0.005. The G and E conditions (planting/sowing season)
      influences the ANF's content. This initial study suggests that early sowing
      reduces the total ANF's content irrespective of genotypes and their growing
      locations.

PMID- 27719918
TI  - Biochemical and biological characterization of two Brassicaceae after their
      commercial expiry date.
AB  - Two Brassicaceae (Eruca sativa, Brassica oleracea var. sabauda) were stored in
      air and under a modified atmosphere for several days after their expiry date and
      then analyzed. The polyphenol content and composition, as well as the antioxidant
      activity of the extracts, were assessed, compared to the fresh products.
      Antimicrobial properties on tester strains (Bacillus cereus, Escherichia coli,
      Staphylococcus aureus and Pseudomonas aeruginosa) and in vitro anti-proliferative
      activity were evaluated. The cabbage extracts exhibited antimicrobial activity
      mainly on the ninth day after the expiry date and retained significant inhibitory
      effects against colon carcinoma (CaCo-2) cells. The rocket salad extract
      exhibited antiproliferative but not antimicrobial activity. Overall, our results
      indicated that they might represent a good source of natural antioxidants with
      antimicrobial and anti-proliferative activity, also after their expiry date,
      suggesting their exploitation for the recovery of important biomolecules used in
      the food and health industry.

PMID- 27719917
TI  - Terahertz sensing of chlorpyrifos-methyl using metamaterials.
AB  - By squeezing electromagnetic energy into small volumes near a metal-dielectric
      interface, plasmonics provide many routes to enhance and manipulate light-matter
      interactions, which presents new strategies for signal enhancing technologies. As
      an extension of the ideas of plasmonics to the terahertz (THz) range,
      metamaterials have shown great potential in sensing applications. In this study,
      terahertz time-domain spectroscopy (THz-TDS) combined with metamaterials was used
      to detect chlorpyrifos-methyl (CM), which is one type of the broad-spectrum
      organophosphorus pesticides. The results demonstrate that sensitivity is greatly
      improved using THz metamaterials, with the limit of detection (LOD) of CM
      reaching 0.204mgL-1, which is lower than the World Health Organization's
      provisional guideline limit for CM in vegetables (1mgL-1). The results indicated
      that THz spectroscopy combined with metamaterials could be a valuable method for
      highly sensitive THz applications, presenting a new strategy for food quality and
      safety control in the future.

PMID- 27719919
TI  - The analysis of the causes of protein precipitate formation in the blanched
      soymilk.
AB  - This paper explored the causes of protein precipitate formation in blanched
      soymilk prepared by blanching soybeans through studying the changes in
      composition and amount of protein particles during its thermal processing.
      Compared with the traditional method of preparing soymilk, blanching changed the
      thermal aggregation behavior of protein particles. Results showed that when
      blanching was applied to soybeans, beta-conglycinin (7S) was denatured in the
      blanched soybeans, which resulted in the fixation and aggregation of 7S prior to
      the grinding processing. Therefore, 7S lost its inhibitory ability on the growth
      of other protein aggregation, explaining the increased insoluble precipitates in
      the blanched soymilk.

PMID- 27719920
TI  - Multi-element analysis of vegetal foodstuff by means of low power total
      reflection X-ray fluorescence (TXRF) spectrometry.
AB  - In this work, an analytical methodology in combination with a low power benchtop
      total reflection X-ray fluorescence (TXRF) system has been developed for multi
      elemental analysis of vegetal materials. An easy and rapid sample preparation
      consisting in suspending 20mg of sample in de-ionized water showed to be the most
      suitable for this kind of samples. However, for comparison purposes, two
      digestion procedures were also applied. A set of fifteen certified reference
      materials and three real vegetal samples were employed for the quantitative
      determination of K, Ca, Mn, Fe, Cu, Zn, Br, Rb, Sr, Pb, As and Sn. All the
      parameters affecting sample preparation and TXRF measurements conditions were
      carefully evaluated. Accurate and precise results were obtained for mid-high Z
      elements (Mn-Sr) using internal standardization as quantification approach, while
      for light Z elements (K and Ca), due to absorption effects, an improvement of
      analytical results by external calibration was necessary.

PMID- 27719921
TI  - Betalains increase vitexin-2-O-xyloside cytotoxicity in CaCo-2 cancer cells.
AB  - Vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L. (BVc) seeds,
      betaxanthin (R1) and betacyanin (R2) fractions from Beta vulgaris var. rubra L.
      (BVr) roots were combined and tested for cytotoxicity in CaCo-2 colon cancer
      cells. XVX was the most cytotoxic molecule, but the combination of XVX with R1
      and R2 significantly prolonged its cytotoxicity. Cytotoxicity was mediated by the
      intrinsic apoptotic pathway, as shown by an increase in Bcl2-like protein 4,
      cleaved Poly ADP-Ribosyl Polymerase 1 and cleaved Caspase 3 levels with a
      parallel decrease in anti-apoptotic protein B-cell leukemia/lymphoma 2 levels. R1
      and R2, used alone or in combination, reduced oxidative stress triggered by H2O2
      in CaCo-2 cells. Betalains dampened cyclooxygenase-2 and interleukin-8 mRNA
      expression after lipopolysaccharide induction in CaCo-2, showing an anti
      inflammatory action. Our results support the use of a cocktail of R1, R2 and XVX
      as a chemopreventive tool against colon cancer.

PMID- 27719922
TI  - Drug-in-cyclodextrin-in-liposomes as a carrier system for volatile essential oil
      components: Application to anethole.
AB  - A combined approach based on cyclodextrin/drug inclusion complex formation and
      loading into liposomes was applied to improve the effectiveness of liposome
      loading with essential oils. Hydroxypropyl-beta-cyclodextrin/ANE (HP-beta-CD/ANE)
      inclusion complexes were prepared and encapsulated into liposomes (ACL). ANE
      double-loaded liposomes (ACL2) were obtained with the HP-beta-CD/ANE complex in
      the aqueous phase and ANE in the organic phase. Liposomes were prepared from
      saturated (Phospholipon 90H) or unsaturated (Lipoid S100) phospholipids and
      characterized for size, polydispersity index, zeta potential, morphology, loading
      rate (LR) and photo- and storage stabilities. All liposome batches were
      nanometric oligolamellar-type vesicles. Compared to ANE-loaded liposomes, ACL
      90H, ACL2-90H and ACL2-S100 displayed significantly increased ANE LR, with ACL2
      S100 exhibiting the highest LR. All formulations provided ANE photoprotection,
      were physically stable after 15months of storage at 4 degrees C (with the
      exception of ACL2-S100), and retained more than 25% of the ANE initially present
      in the liposome suspensions.

PMID- 27719923
TI  - Immunogenic inhibition of prominent ruminal bacteria as a means to reduce
      lipolysis and biohydrogenation activity in vitro.
AB  - Lipolysis and biohydrogenation in ruminal animals promote the accumulation of
      saturated fatty acids in their meat and milk. Antibodies were generated against
      key ruminal lipase contributors Anaerovibrio lipolyticus, Butyrivibrio
      fibrisolvens, Propionibacterium avidum and acnes. An anti-Pseudomonas lipase
      antibody was generated to determine if an antibody against a purified protein
      would be more effective. Each bacterium was cultured and assayed without or with
      increasing levels of each antibody. Butyrivibrio fibrisolvens H17C also
      participates in biohydrogenation and therefore the antibody was tested to
      determine if it could effectively reduce biohydrogenation. Butyrivibrio
      fibrisolvens was assayed without and with the anti-B. fibrisolvens antibody and
      linoleic or alpha-linolenic acid. All antibodies were effective at reducing
      lipolysis with the anti-Pseudomonas lipase averaging a 78% reduction. The anti-B.
      fibrisolvens showed a tendency for a reduction (P=0.0713) in biohydrogenation
      products of alpha-linolenic acid. Results demonstrate that lipolysis and
      biohydrogenation can be immunologically inhibited in vitro.

PMID- 27719924
TI  - An LC-MS/MS method for multi-mycotoxin quantification in cow milk.
AB  - The simultaneous quantification of 15 mycotoxins in cow milk by liquid
      chromatography-mass spectrometry, is presented. Extraction was performed with
      acidified acetonitrile, followed by a cleanup step with sodium acetate. During
      validation limits of detection (LOD) and quantification, linearity, precision,
      accuracy, recovery, matrix effect, and stability were studied. LOD values were
      between 0.02 and 10.14ng/mL for aflatoxins M1, B1, B2, G1, G2, ochratoxins A and
      B, HT-2 and T-2 toxins, deepoxy-deoxynivalenol, zearalenone, sterigmatocystin and
      fumonisins B1, B2 and B3. Recovery values were between 82.6 and 94.4% for all the
      mycotoxins, except for fumonisins. The recovery values for fumonisins were
      between 42.1% and 64.6%. Matrix effect, between 25.5 and 96.8%, appeared for all
      of the mycotoxins, especially for deepoxy-deoxynivalenol, zearalenone and
      sterigmatocystin. The validated method achieves the quantification of those
      mycotoxins of major concern and mycotoxins that are not frequently studied in
      milk, such as fumonisins, sterigmatocystin or ochratoxin B.

PMID- 27719925
TI  - Extraction optimization and identification of anthocyanins from Nitraria
      tangutorun Bobr. seed meal and establishment of a green analytical method of
      anthocyanins.
AB  - This study aimed to extract and identify anthocyanins from Nitraria tangutorun
      Bobr. seed meal and establish a green analytical method of anthocyanins.
      Ultrasound-assisted extraction of anthocyanins from N. tangutorun seed meal was
      optimized using response surface methodology. Extraction at 70 degrees C for
      32.73 min using 51.15% ethanol rendered an extract with 65.04mg/100g of
      anthocyanins and 947.39mg/100g of polyphenols. An in vitro antioxidant assay
      showed that the extract exhibited a potent DPPH radical-scavenging capacity.
      Eight anthocyanins in N. tangutorun seed meal were identified by HPLC-MS, and the
      main anthocyanin was cyanidin-3-O-(trans-p-coumaroyl)-diglucoside (18.17mg/100g).
      A green HPLC-DAD method was developed to analyse anthocyanins. A mixtures of
      ethanol and a 5% (v/v) formic acid aqueous solution at a 20:80 (v/v) ratio was
      used as the optimized mobile phase. The method was accurate, stable and reliable
      and could be used to investigate anthocyanins from N. tangutorun seed meal.

PMID- 27719926
TI  - Bioactive peptides from Atlantic salmon (Salmo salar) with angiotensin converting
      enzyme and dipeptidyl peptidase IV inhibitory, and antioxidant activities.
AB  - The pH shift method was utilised for the recovery of proteins from salmon
      trimmings (ST), yielding 93% (w/w) protein. ST protein (STP) hydrolysates were
      generated with different enzyme preparations. STP incubated with Corolase PP for
      1h (STP-C1) had the most potent angiotensin converting enzyme (ACE) and
      dipeptidyl peptidase IV (DPP-IV) inhibitory and oxygen radical absorbance
      capacity (ORAC) activities. Analysis of fractions of STP-C1 using UPLC-MS/MS
      identified sixteen peptides/amino acids. Tyr-Pro had the highest ACE inhibitory
      activity (ACE IC50=5.21+/-0.94MUM). The highest DPP-IV inhibitory activity was
      found with the amino acid Tyr (DPP-IV IC50=75.15+/-0.84MUM). Val-Pro had the
      highest ORAC activity (19.45+/-2.15MUmol of TEg-1). To our knowledge, the
      peptides Gly-Pro-Ala-Val, Val-Cys, and Phe-Phe have not been previously
      identified to have the activities tested in this study. These results indicate
      that STP hydrolysates are potential sources of bioactive peptides.

PMID- 27719927
TI  - Characterization of neural network generalization in the determination of pH and
      anthocyanin content of wine grape in new vintages and varieties.
AB  - The generalization ability of hyperspectral imaging combined with neural networks
      (NN) in estimating pH and anthocyanin content during ripening was evaluated for
      vintages and varieties not employed in the NN creation. A NN, from a previously
      published work, trained with grape samples of Touriga Franca (TF) variety
      harvested in 2012 was tested with TF from 2013 and two new varieties, Touriga
      Nacional (TN) and Tinta Barroca (TB) from 2013. Each sample contained a small
      number of whole berries. The present work results suggest that, under certain
      conditions, it might be possible for the NN to provide for new vintages and
      varieties results comparable to those of the vintages and varieties employed in
      the NN training. For pH, the results are state-of-the-art for the new vintage and
      varieties tested. For anthocyanin, generalization is bad for TB from 2013 but
      presents state-of-the-art absolute percentage error for TF and TN from 2013.

PMID- 27719928
TI  - Metabolomic analyses of banana during postharvest senescence by 1H-high
      resolution-NMR.
AB  - Banana is a tropical fruit widely accepted by people over the world. Its chemical
      composition is critical for its organoleptic properties and nutritional value. In
      this work, the metabolite changes during postharvest senescence were investigated
      using NMR spectroscopy. The 1D and 2D NMR spectroscopic information revealed the
      primary and secondary metabolites in banana fruit, including organic acids, amino
      acids, carbohydrates and phenolics. Bananas at five senescence stages showed
      similar chemical profiles, but the levels of the individual compounds varied to a
      large extent. The principal metabolites responsible for postharvest senescence of
      banana were valine, alanine, aspartic acid, choline, acetate, glucose, malic
      acid, gallic acid and dopamine. At stage V, ethanol was present due to the
      conversion of glucose. Salsolinol was generated due to the conversion of
      dopamine. This was a characteristic marker for the postharvest senescence of
      banana fruit.

PMID- 27719929
TI  - How to predict the sugariness and hardness of melons: A near-infrared
      hyperspectral imaging method.
AB  - Hyperspectral imaging (HSI) in the near-infrared (NIR) region (900-1700nm) was
      used for non-intrusive quality measurements (of sweetness and texture) in melons.
      First, HSI data from melon samples were acquired to extract the spectral
      signatures. The corresponding sample sweetness and hardness values were recorded
      using traditional intrusive methods. Partial least squares regression (PLSR),
      principal component analysis (PCA), support vector machine (SVM), and artificial
      neural network (ANN) models were created to predict melon sweetness and hardness
      values from the hyperspectral data. Experimental results for the three types of
      melons show that PLSR produces the most accurate results. To reduce the high
      dimensionality of the hyperspectral data, the weighted regression coefficients of
      the resulting PLSR models were used to identify the most important wavelengths.
      On the basis of these wavelengths, each image pixel was used to visualize the
      sweetness and hardness in all the portions of each sample.

PMID- 27719930
TI  - Highly selective and sensitive determination of several antioxidants in human
      breast milk using high-performance liquid chromatography based on Ag(III) complex
      chemiluminescence detection.
AB  - Ascorbic acid (AA), uric acid (UA) and glutathione (GSH) are the most important
      water-soluble antioxidants. The concentrations of GSH and glutathione disulfide
      (GSSG) and their molar ratio are the indicators of oxidative stress. Little is
      known about the contents of UA, GSH and GSSG in human milk; a reliable and
      sensitive method to monitor the concentrations of the four compounds
      simultaneously in human milk is of critical importance. A new method for
      separation and quantification of these water-soluble antioxidants by HPLC coupled
      with Ag(III) chemiluminescence detector has been developed in this work with
      better recoveries. The antioxidants contents were determined in different times
      of lactation utilizing this method. The results show that the levels of AA, UA,
      GSH and GSH/GSSG of human colostrum are significantly higher than those of mature
      milk (P<0.05). It is concluded that colostrum contains more water-soluble
      antioxidants than mature milk.

PMID- 27719931
TI  - Antibacterial polyketides from Bacillus amyloliquefaciens associated with edible
      red seaweed Laurenciae papillosa.
AB  - Heterotrophic Bacillus amyloliquefaciens associated with edible red seaweed,
      Laurenciae papillosa was used to isolate antibacterial polyketide compounds.
      Antibacterial activity studies integrated with the outcome obtained by polyketide
      synthetase (pks) coding genes established that seaweed-affiliated bacterial flora
      had a wide-ranging antibacterial activities and potential natural product
      diversity, which proved that the bacterium is valuable reservoir of novel
      bioactive metabolites. Bioactivity-guided isolation of 3-(octahydro-9-isopropyl
      2H-benzo[h]chromen-4-yl)-2-methylpropyl benzoate and methyl 8-(2-(benzoyloxy)
      ethyl)-hexahydro-4-((E)-pent-2-enyl)-2H-chromene-6-carboxylate of polyketide
      origin, with activity against human opportunistic food pathogenic microbes, have
      been isolated from the ethyl acetate extract of B. amyloliquefaciens. Structure
      activity relationship analysis revealed that hydrophobic descriptor of the
      polyketide compounds significantly contribute towards its antibacterial activity.
      Seaweed-associated microorganisms were shown to represent a potential source of
      antimicrobial compounds for food and health benefits. The antibacterial
      polyketide compounds described in the present study may find potential
      applications in the food industry to reduce food-borne pathogens.

PMID- 27719932
TI  - Sardinian Boraginaceae are new potential sources of gamma-linolenic acid.
AB  - The aim of this work was to establish the richness in gamma-linolenic acid (GLA,
      18:3n6) and stearidonic acid (SDA, 18:4n3) of several Sardinian Boraginaceae
      species. To this end, seeds of selected species were collected from their natural
      habitats and analysed. The highest GLA contents were found in the seed oils of
      two endemic Borago taxa, i.e. B. morisiana (24.4 and 24.6% GLA of total fatty
      acids for samples from San Pietro Island and Sardinia Island, respectively), and
      22.9% GLA for B. pygmaea. Both Borago species contained more GLA than B.
      officinalis collected in the same ecosystems. SDA was found in significant
      amounts in Echium plantagineum seed oil from the Lattias Mountains (15% SDA of
      total fatty acids). It is notable that both Borago GLA-rich species are under
      threat of extinction, thus revealing the importance of the preservation of the
      natural Sardinian ecosystems for endangered species and human health.

PMID- 27719933
TI  - Antiradical activity of delphinidin, pelargonidin and malvin towards hydroxyl and
      nitric oxide radicals: The energy requirements calculations as a prediction of
      the possible antiradical mechanisms.
AB  - Naturally occurring flavonoids, delphinidin, pelargonidin and malvin, were
      investigated experimentally and theoretically for their ability to scavenge
      hydroxyl and nitric oxide radicals. Electron spin resonance (ESR) spectroscopy
      was used to determine antiradical activity of the selected compounds and M05-2X/6
      311+G(d,p) level of theory for the calculation of reaction enthalpies related to
      three possible mechanisms of free radical scavenging activity, namely HAT, SET-PT
      and SPLET. The results obtained show that the molecules investigated reacted with
      hydroxyl radical via both HAT and SPLET in the solvents investigated. These
      results point to HAT as implausible for the reaction with nitric oxide radical in
      all the solvents investigated. SET-PT also proved to be thermodynamically
      unfavourable for all three molecules in the solvents considered.

PMID- 27719934
TI  - Multi-mycotoxin stable isotope dilution LC-MS/MS method for Fusarium toxins in
      beer.
AB  - A stable isotope dilution LC-MS/MS multi-mycotoxin method was developed for 12
      different Fusarium toxins including modified mycotoxins in beer (deoxynivalenol-3
      glucoside, deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyl-deoxynivalenol, HT2
      toxin, T2-toxin, enniatin B, B1, A1, A, beauvericin and zearalenone). As sample
      preparation and purification of beer a combined solid phase extraction for
      trichothecenes, enniatins, beauvericin and zearalenone was firstly developed. The
      validation of the new method gave satisfying results: intra-day and inter-day
      precision and recoveries were 1-5%, 2-8% and 72-117%, respectively. In total, 61
      different organic and conventional beer samples from Germany and all over the
      world were analyzed by using the newly developed multi-mycotoxin method. In
      summary, deoxynivalenol, deoxynivalenol-3-glucoside, 3-acetyldeoxynivaleneol and
      enniatin B were quantified in rather low contents in the investigated beer
      samples. None of the other monitored Fusarium toxins like 15
      acetyldeoxynivalenol, HT2- and T2-toxin, zearalenone, enniatin B1, A1, A or
      beauvericin were detectable.

PMID- 27719935
TI  - Phosphorylation prevents in vitro myofibrillar proteins degradation by MU
      calpain.
AB  - Myofibrillar proteins degradation contributes to meat tenderisation during post
      mortem ageing. Protein phosphorylation has been revealed to be associated with
      meat tenderness in recent years. This study was undertaken to determine the
      impact of myofibrillar proteins phosphorylation on the degradation susceptibility
      by MU-calpain. Myofibrillar proteins were first incubated with protein kinase A
      (PKA) or alkaline phosphatase (AP) to increase or decrease the phosphorylation
      level, following MU-calpain hydrolysis. Myosin heavy chain, actin, desmin and
      troponin T showed different levels of degradation in control, AP and PKA groups
      under different Ca2+ concentrations. Generally, more degradation products were
      detected with the increase of Ca2+ concentration. Compared to the control, the
      protein degradation was higher in AP-treated group and lower in PKA-treated
      group. This study shows that phosphorylation prevents proteolytic susceptibility
      of myofibrillar proteins to degradation by MU-calpain, indicating that protein
      phosphorylation plays an important role in meat tenderisation during post-mortem
      ageing.

PMID- 27719936
TI  - A dual antibacterial mechanism involved in membrane disruption and DNA binding of
      2R,3R-dihydromyricetin from pine needles of Cedrus deodara against Staphylococcus
      aureus.
AB  - The antibacterial activity and mechanism of 2R,3R-dihydromyricetin (DMY) against
      Staphylococcus aureus were investigated. The minimum inhibitory concentration of
      DMY against S. aureus was 0.125mg/ml, and the growth inhibitory assay also
      revealed that DMY showed a potent antibacterial activity against S. aureus.
      Massive nucleotide leakage and flow cytometric analysis demonstrated that DMY
      disrupted the membrane integrity of S. aureus. Morphological changes and membrane
      hyperpolarization of S. aureus cells treated with DMY further suggested that DMY
      destroyed cell membrane. Meanwhile, DMY probably interacted with membrane lipids
      and proteins, causing a significant reduction in membrane fluidity and changes in
      conformation of membrane protein. Moreover, DMY could interact with S. aureus DNA
      through the groove binding mode. Overall, the results suggested that DMY could be
      applied as a candidate for the development of new food preservatives as it
      achieved bactericidal activity by damaging cell membrane and binding to
      intracellular DNA.

PMID- 27719937
TI  - Changes in phenolic content of commercial potato varieties through industrial
      processing and fresh preparation.
AB  - Reported content and process stability of phenolics in potato products is
      inconsistent. Changes in phenolic content of select varieties through fresh and
      industrial preparation/reconstitution were assessed. Total chlorogenic acids
      (CQAs) ranged from 43 to 953mg/100g dw and were more concentrated in pigmented
      compared to white/yellow-fleshed potatoes. Anthocyanin (ANC) content ranged from
      18.6 to 22.9mg/100g dw and were mainly present in the flesh of pigmented
      potatoes. Retention of phenolics through commercial processing ranged from 49 to
      85% for pigmented varieties and 32-55% for white/yellow. CQA levels were reduced
      through processing but to a greater extent in white relative to pigmented
      potatoes. ANCs were well retained through industrial processing of pigmented
      potatoes (79-129%). Levels of CQA were significantly (p<0.05) lower in some
      industrially versus freshly processed products but not for all products. While
      some differences exist, overall, industrially processed potato products compare
      favorably to fresh preparation in levels and recovery of phenolics.

PMID- 27719938
TI  - Protection of folic acid through encapsulation in mesoporous silica particles
      included in fruit juices.
AB  - Folic acid (FA) is a synthetic vitamin commonly used for food fortification.
      However, its vulnerability to processing and storage implies loss of efficiency,
      which would induce over-fortification by processors to obtain a minimum dose upon
      consumption. Recent studies have indicated potential adverse effects of FA
      overdoses, and FA protection during processing and storage could lead to more
      accurate fortification. In addition, sustained vitamin release after consumption
      would help improve its metabolism. The objective of this work was to study
      controlled FA delivery and stability in fruit juices to reduce potential over
      fortification risks by using gated mesoporous silica particles (MSPs). The
      obtained results indicated that FA encapsulation in MSPs significantly improved
      its stability and contributed to controlled release after consumption by
      modifying vitamin bioaccessibility. These results confirmed the suitability of
      MSPs as support for controlled release and protection of bioactive molecules in
      food matrices in different food production and storage stages.

PMID- 27719939
TI  - Development of a biosensor telemetry system for monitoring fermentation in craft
      breweries.
AB  - The development and applications of biosensors in the food industry has had a
      rapid grown due to their sensitivity, specificity and simplicity of use with
      respect to classical analytical methods. In this study, glucose and ethanol
      amperometric biosensors integrated with a wireless telemetry system were
      developed and used for the monitoring of top and bottom fermentations in beer
      wort samples. The collected data were in good agreement with those obtained by
      reference methods. The simplicity of construction, the low cost and the short
      time of analysis, combined with easy interpretation of the results, suggest that
      these devices could be a valuable alternative to conventional methods for
      monitoring fermentation processes in the food industry.

PMID- 27719940
TI  - Mechanisms and kinetics of tryptophan N-nitrosation in a gastro-intestinal model.
AB  - The reaction of nitrite with different amino acids containing secondary amino
      groups was tested under simulated in-vitro conditions of the digestive tract.
      After treatment, tryptophan was the only amino acid that exhibited specific UV
      absorbance of nitrosamines at 335nm, supporting the assumption that it is the
      main source of endogenous nitrosamines. The combined effect of pH (from 2 to 6.5)
      and nitrite (from 0.1 to 20mM) was analyzed and the mechanisms and kinetic laws
      of tryptophan N-nitrosation were determined. The model was then completed by the
      addition of iron and various antioxidants in concentrations reflecting different
      diets. The results clearly demonstrated that, in the presence of iron, large
      amounts of N-nitroso-tryptophan can be formed even at neutral pH, as in the
      intestine. Antioxidants (ascorbic acid, trolox C, beta carotene, chlorogenic
      acid, phytic acid and butylated-hydroxytoluene) had various impacts on the extent
      of N-nitrosation, depending on the iron level.

PMID- 27719941
TI  - Chemometric approach to develop frying stable sunflower oil blends stabilized
      with oleoresin rosemary and ascorbyl palmitate.
AB  - The frying performance of sunflower oil blends (SOBs) stabilized with oleoresin
      rosemary (Rosmarinus officinalis L.) (ROSM) (200-1500mg/kg) and ascorbyl
      palmitate (AP) (100-300mg/kg) were tested for 18hopen pan-frying. Sunflower oil
      with TBHQ (SOTBHQ) (200mg/kg) and without additives (SOcontrol) served as
      positive and negative controls, respectively. The frying stability was monitored
      over time by estimating the levels of conjugated dienes, total polar compounds,
      polymeric compounds viz., triglyceride polymers, dimers, oxidized triglyceride
      monomers, diglycerides and free fatty acids, and induction period based on
      Rancimat. Chemometric tools were used to classify the oil samples based on frying
      stability. Thermo-oxidative changes were reduced significantly for blends
      stabilized with ROSM and AP (p<0.05). Principal component analysis (PCA) and
      hierarchical cluster analysis (HCA) distinguished SOBs from positive controls. A
      formulation consisting of 1309.62 and 129.29mg/kg of ROSM and AP, respectively,
      was optimized using a hybrid PCA-RSM approach.

PMID- 27719942
TI  - Synthesis of medium-chain length capsinoids from coconut oil catalyzed by Candida
      rugosa lipases.
AB  - A commercial preparation of Candida rugosa lipases (CRL) was tested for the
      production of capsinoids by esterification of vanillyl alcohol (VA) with free
      fatty acids (FA) and coconut oil (CO) as acyl donors. Screening of FA chain
      length indicated that C8-C12 FA (the most common FA found in CO triglycerides)
      are the best acyl-donors, yielding 80-85% of their specific capsinoids. Hence,
      when CO, which is rich in these FA, was used as the substrate, a mixture of
      capsinoids (vanillyl caprylate, vanillyl decanoate and vanillyl laurate) was
      obtained. The findings presented here suggest that our experimental method can be
      applied for the enrichment of CO with capsinoids, thus giving it additional
      health promoting properties.

PMID- 27719943
TI  - Effect of yeast mannan treatments on ripening progress and modification of cell
      wall polysaccharides in tomato fruit.
AB  - Yeast mannan treatments effectively delayed colour change and firmness decline
      and inhibited ethylene production in two cultivars of tomato fruit during
      storage. The yeast mannan treatment maintained the integrity of tomato pericarp
      cell wall architecture and suppressed the modification of water-soluble and
      insoluble pectic polysaccharides in the cell wall. A decrease in the neutral
      sugars, including d-galactose, l-arabinose and l-rhamnose, in water-insoluble
      pectin and an increase in these sugars in water-soluble pectin were inhibited by
      yeast mannan. The contents of d-xylose and d-mannose in the hemicellulose
      fraction were significantly higher in the yeast mannan-treated fruit after
      storage. The activities of several cell wall-modifying enzymes, including
      pectinmethylesterase, polygalacturonase and beta-galactosidase, were suppressed
      in fruit treated with yeast mannan during storage. Overall, the yeast mannan
      induced delay in the ripening progress of tomato fruit might occur via the strong
      suppression of ethylene synthesis, causing inhibition of solubilization and
      depolymerization of cell wall polysaccharides.

PMID- 27719944
TI  - Development, validation and application of an UFLC-DAD-ESI-MS method for
      determination of carbonyl compounds in soybean oil during continuous heating.
AB  - A method was developed for the extraction and UFLC-DAD-ESI-MS analysis of
      carbonyl compounds (CCs) in oils heated to 180 degrees C. Different parameters
      were evaluated, and the best results were 1.5ml of acetonitrile as the extraction
      solvent, manual stirring for 3min and 30min of sonication time. The method was
      validated using soybean oil samples spiked with CCs at concentration levels
      ranging from 0.2 to 10.0MUg.mL-1. The average recoveries in the lowest
      concentration level ranged from 70.7% to 85.0%. Detection limits ranged from 0.03
      to 0.1MUg.mL-1, and the quantification limit was 0.2MUg.mL-1 for all compounds.
      When the method was applied to samples of heated oil, the CCs identified were 4
      hydroxy-2-nonenal, 2,4-decadienal, 2,4-heptadienal, 4-hydroxy -2-hexenal,
      acrolein, 2-heptenal, 2-octenal, 4,5-epoxy-2-decadal, 2-decenal, and 2-undecenal,
      with the first three mentioned presenting the highest mean concentrations after
      heating, specifically 36.9, 34.8 and 22.6MUg.g-1 of oil, respectively.

PMID- 27719945
TI  - Ultrastructural deposition forms and bioaccessibility of carotenoids and
      carotenoid esters from goji berries (Lycium barbarum L.).
AB  - Goji berries (Lycium barbarum L.) have been known to contain strikingly high
      levels of zeaxanthin, while the physical deposition form and bioaccessibility of
      the latter was yet unknown. In the present study, we associated ripening-induced
      modifications in the profile of carotenoids with fundamental changes of the
      deposition state of carotenoids in goji berries. Unripe fruit contained common
      chloroplast-specific carotenoids being protein-bound within chloroplastidal
      thylakoids. The subsequent ripening-induced transformation of chloroplasts to
      tubular chromoplasts was accompanied by an accumulation of up to 36mg/100g FW
      zeaxanthin dipalmitate and further minor xanthophyll esters, prevailing in a
      presumably liquid-crystalline state within the nano-scaled chromoplast tubules.
      The in vitro digestion unraveled the enhanced liberation and bioaccessibility of
      zeaxanthin from these tubular aggregates in goji berries as compared to protein
      complexed lutein from spinach. Goji berries therefore might represent a more
      potent source of macular pigments than green leafy vegetables like spinach.

PMID- 27719946
TI  - Bacterial community succession and metabolite changes during doubanjiang-meju
      fermentation, a Chinese traditional fermented broad bean (Vicia faba L.) paste.
AB  - Doubanjiang-meju, a major ingredient of Chinese fermented food for several
      centuries, is produced using broad bean, wheat flour and salt. In this study, we
      investigated prokaryotic community succession and metabolite changes using high
      throughput sequencing and 1H-NMR methods. After 35 days, bacterial communities,
      except Lactobacillus and Acinetobacter, were relatively stable until the end of
      fermentation, and consisted predominantly of the genera Tetragenococcus,
      Lactobacillus, Staphylococcus, Acinetobacter, Pseudomonas and Streptococcus.
      Glucose, arabinose, fructose and mannitol were identified as major sugars,
      lactate and acetate as major organic acids, and amino acids as the major nitrogen
      compounds present in doubanjiang-meju. Correlation analysis revealed important
      links between bacterial populations and metabolites, e.g., Pseudomonas was
      significantly correlated with 10 nitrogenous metabolites, while Streptococcus was
      significantly correlated with six carbonic metabolite and eight nitrogenous
      metabolites. These results not only revealed bacterial succession and dynamic
      changes in metabolites as well as pH and color, but also elucidated their
      relationships during the doubanjiang-meju fermentation.

PMID- 27719948
TI  - Prediction of peanut protein solubility based on the evaluation model established
      by supervised principal component regression.
AB  - Supervised principal component regression (SPCR) analysis was adopted to
      establish the evaluation model of peanut protein solubility. Sixty-six peanut
      varieties were analysed in the present study. Results showed there was intimate
      correlation between protein solubility and other indexes. At 0.05 level, these 11
      indexes, namely crude fat, crude protein, total sugar, cystine, arginine,
      conarachin I, 37.5kDa, 23.5kDa, 15.5kDa, protein extraction rate, and kernel
      ratio, were correlated with protein solubility and were extracted to for
      establishing the SPCR model. At 0.01 level, a simper model was built between the
      four indexes (crude protein, cystine, conarachin I, and 15.5kDa) and protein
      solubility. Verification results showed that the coefficients between theoretical
      and experimental values were 0.815 (p<0.05) and 0.699 (p<0.01), respectively,
      which indicated both models can forecast the protein solubility effectively. The
      application of models was more convenient and efficient than traditional
      determination method.

PMID- 27719947
TI  - Determination of trace thiophanate-methyl and its metabolite carbendazim with
      teratogenic risk in red bell pepper (Capsicumannuum L.) by surface-enhanced Raman
      imaging technique.
AB  - Surface-enhanced Raman scattering (SERS) imaging coupling with multivariate
      analysis in spectral region of 200 to 1800cm-1 was developed to quantify and
      visualize thiophanate-methyl (TM) and its metabolite carbendazim residues in red
      bell pepper (Capsicum annuum L.). Least squares support vector machines (LS-SVM)
      and support vector machines (SVM) models based on seven optimized characteristic
      peaks that showed SERS effects of TM and its metabolite carbendazim residues were
      employed to establish prediction models. SERS spectra with first derivative (1st)
      and second derivative (2nd) method were subsequently compared and the optimized
      model of 1st-LS-SVM acquired showed the best performance (RPD=6.08, R2P=0.986 and
      RMSEP=0.473). The results demonstrated that SERS imaging with multivariate
      analysis had the potential for rapid determination and visualization of the trace
      TM and its metabolite carbendazim residues in complex food matrices.

PMID- 27719949
TI  - Physicochemical properties of maca starch.
AB  - Maca (Lepidium meyenii Walpers) is gaining research attention due to its unique
      bioactive properties. Starch is a major component of maca roots, thus
      representing a novel starch source. In this study, the properties of three maca
      starches (yellow, purple and black) were compared with commercially maize,
      cassava, and potato starches. The starch granule sizes ranged from 9.0 to 9.6MUm,
      and the granules were irregularly oval. All the maca starches presented B-type X
      ray diffraction patterns, with the relative degree of crystallinity ranging from
      22.2 to 24.3%. The apparent amylose contents ranged from 21.0 to 21.3%. The onset
      gelatinization temperatures ranged from 47.1 to 47.5 degrees C as indicated by
      differential scanning calorimetry. Significant differences were observed in the
      pasting properties and textural parameters among all of the studied starches.
      These characteristics suggest the utility of native maca starch in products
      subjected to low temperatures during food processing and other industrial
      applications.

PMID- 27719950
TI  - Synergistic effects of light quality, carbon dioxide and nutrients on metabolite
      compositions of head lettuce under artificial growth conditions mimicking a plant
      factory.
AB  - Carbon dioxide (CO2), nutrient supply, and light quality are amongst the major
      controlling factors to improve the biomass production and nutritional outputs in
      plant factory. The present study employed CE-MS to investigate the effects of
      high CO2, nutrient formulation, and LED on the accumulation of primary
      metabolites in head lettuce. Results suggested that high CO2 (1000ppm) and
      nutrient supply enhanced both the biomass and some amino acids. Hierarchical
      clustering analysis was used to evaluate effects of red LED in combination with
      high CO2 and Hoagland's formulation; distinctive cluster formation contained 14
      amino acids (mostly branched-chain and aromatic amino acids, histidine and
      arginine). Thus, simultaneous treatments of monochromatic LED, high CO2 and
      nutrient formulation improved the amino acids accumulation, and likely reduced
      the inorganic nitrogen sources in planta.

PMID- 27719952
TI  - LED Blue Light-induced changes in phenolics and ethylene in citrus fruit:
      Implication in elicited resistance against Penicillium digitatum infection.
AB  - The objective was to investigate whether LED Blue Light (LBL) induces changes in
      phenolics and ethylene production of sweet oranges, and whether they participate
      in LBL-elicited resistance against the most important postharvest pathogen
      (Penicillium digitatum) of citrus fruit. The expression of relevant genes of the
      phenylpropanoid and ethylene biosynthetic pathways during elicitation of
      resistance was also determined. Different LBL (wavelength 450nm) quantum fluxes
      were used within the 60-630MUmolm-2s-1 range. The HPLC analysis showed that the
      most relevant increase in phenylpropanoids occurred in scoparone, which markedly
      increased 3days after exposing fruits to a very high quantum flux (630MUmolm-2s
      1) for 18h. However, phenylpropanoids, including scoparone, were not critical
      factors in LBL-induced resistance. The genes involved in ethylene biosynthesis
      were differentially regulated by LBL. Ethylene is not involved in elicited
      resistance, although high LBL levels increased ethylene production in only 1h.

PMID- 27719951
TI  - Triacylglycerol compositions of sunflower, corn and soybean oils examined with
      supercritical CO2 ultra-performance convergence chromatography combined with
      quadrupole time-of-flight mass spectrometry.
AB  - A supercritical CO2 ultra-performance convergence chromatography (UPC2) system
      was utilized with a quadrupole time-of-flight mass spectrometry (Q-TOF MS) to
      examine the triacylglycerol compositions of sunflower, corn and soybean oils.
      UPC2 provided an excellent resolution and separation for the triacylglycerols,
      while the high performance Q-TOF MS system was able to provide the molecular
      weight and fragment ions information for triacylglycerol compound
      characterization. A total of 33 triacylglycerols were identified based on their
      elementary compositions and MS2 fragment ion profiles, and their levels in the
      three oils were estimated. The combination of UPC2 and Q-TOF MS may determine
      triacylglycerol compositions for oils and fats, and provide sn-position
      information for fatty acids, which may be important for food nutritional value
      and stability.

PMID- 27719953
TI  - Protein precipitating capacity and antioxidant activity of Turkish Tombul
      hazelnut phenolic extract and its fractions.
AB  - Natural (raw) hazelnut was extracted with 80% (v/v) acetone to obtain crude
      phenolic extract that was then fractionated for elution of low-molecular weight
      (LMW) and high-molecular weight (HMW) fractions. LMW fraction was further
      purified (LWM-FP) to remove sugars and organic acids. The crude extract and its
      fractions were determined by measuring their protein precipitating capacity (PPC)
      using two different proteins [bovine serum albumin (BSA) and gelatin], molecular
      weights, total phenolics, condensed tannins, and various antioxidant activities.
      Significant differences (p<0.05) existed in the contents of total phenolics,
      condensed tannins, antioxidant activities, and PPC among the crude extract and
      fractions, albeit to different extends. BSA and gelatin was effectively
      precipitated by HMW fraction. HMW fraction had the highest total phenolics,
      condensed tannins, and antioxidant activities, followed by crude extract, LWM-FP,
      and LMW, respectively. The present study suggests that HMW fraction could be
      utilised as a source of polyphenols for the food industry.

PMID- 27719954
TI  - Cytoprotective effect of seaweeds with high antioxidant activity from the Peniche
      coast (Portugal).
AB  - Screening of antioxidant potential of dichloromethane and methanolic extracts of
      twenty-seven seaweeds from the Peniche coast was performed by: total phenolic
      contents (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity
      and oxygen radical absorbance capacity (ORAC). Seaweeds revealing the highest
      antioxidant activity were screened for cytoprotective potential in MCF-7 cells,
      including the mitochondrial membrane potential analysis and the caspase-9
      activity. High correlation was found between TPC of seaweed extracts and their
      scavenging capacity on DPPH and peroxyl radicals. The highest antioxidant
      activity was displayed by the methanolic fraction of brown seaweeds belonging to
      Fucales, however Ulva compressa presented the highest cytoprotective effect by
      blunting the apoptosis process. These results suggest that high antioxidant
      activity may not be directly related with high cytoprotective potential. Thus,
      seaweeds reveal to be a promising source of compounds with potential against
      oxidative stress.

PMID- 27719956
TI  - Comments on "Sphingoid esters from the molecular distillation of squid oil: A
      preliminary bioactivity determination".

PMID- 27719955
TI  - Efficient identification of flavones, flavanones and their glycosides in routine
      analysis via off-line combination of sensitive NMR and HPLC experiments.
AB  - We present a standardized, straightforward and efficient approach applicable in
      routine analysis of flavonoids combining sensitive NMR and HPLC experiments. The
      determination of the relative configuration of sugar moieties usually requires
      the acquisition of 13C NMR shift values. We use a combination of HPLC and
      sensitive NMR experiments (1D-proton, 2D-HSQC) for the unique identification of
      known flavones, flavanones, flavonols and their glycosides. Owing to their broad
      range of polarity, we developed HPLC and UHPLC methods (H2O/MeOH/MeCN/HCOOH)
      which we applied and validated by analyzing 46 common flavones and flavanones and
      exemplified for four plant extracts. A searchable data base is provided with full
      data comprising complete proton and carbon resonance assignments, expansions of
      HSQC-spectra, HPLC parameters (retention time, relative retention factor), UV/Vis
      and mass spectral data of all compounds, which enables a rapid identification and
      routine analysis of flavones and flavanones from plant extracts and other
      products in nutrition and food chemistry.

PMID- 27719957
TI  - Corrigendum to "Origin assignment by multi-element stable isotopes of lamb
      tissues" [Food Chem. 213 (2016) 675-681].

PMID- 27719958
TI  - Mycotoxin analysis of industrial beers from Brazil: The influence of fumonisin B1
      and deoxynivalenol in beer quality.
AB  - Worldwide, barley is the main source of carbohydrate in the brewing process.
      However, corn is often used as an adjunct to improve and accelerate the
      fermentation process. Considering that, these two substrates are susceptible to
      fungal contamination as well as mycotoxins. The objective of the current study is
      to determine the incidence of the mycotoxins deoxynivalenol (DON) and fumonisin
      B1 (FB1) in industrial beers. The method applied for mycotoxin analyses included
      high performance liquid chromatography. The mean levels for recovery experiments
      were 89.6% for DON and 93.3% for FB1. DON was not detected in any of the analyzed
      samples whereas FB1 was found in 49% of the 114 samples. The current survey
      demonstrated levels of FB1 contamination in industrial beer, possibly due to the
      addition of contaminated adjuncts. It is necessary to establish maximum levels of
      mycotoxins in beer in Brazil and other countries in order to reduce health risks.

PMID- 27719959
TI  - Nutritional composition and antioxidant properties of traditional Italian dishes.
AB  - This work aims at evaluating the main nutrients (proximate, minerals), their
      contribution for Dietary Reference Values in Italian population, and the
      antioxidant properties of some popular dishes prepared in a dedicated lab
      kitchen: spaghetti alle vongole, pomodori al riso, gateau di patate, carciofi
      alla romana, pan di Spagna. Results showed that nutrient contents and energy
      value varied extensively because of the variety and the nature of ingredients in
      the analyzed dishes, and thus defined different daily nutrient intakes and their
      association with health effects. A serving portion of either spaghetti alle
      vongole or carciofi alla romana showed to contribute to the daily nutritional
      recommendations respectively, with an appreciable percentage of available
      carbohydrates (30-22%) and a considerable content of dietary fibre (91%). Gateau
      di patate was particularly rich in calcium (343mg), both contributing 34% of the
      recommended intake, in addition to appreciable content of phosphorus and zinc.
      With regards to spaghetti alle vongole, pomodori al riso, gateau di patate and
      pan di Spagna, extractable polyphenols contributed less than 15% to total
      antioxidant activity, and hydrolysable polyphenols give a major contribution;
      carciofi alla romana showed an inverse trend. Findings provide an important
      contribution to the update of Italian Food Composition Databases.

PMID- 27719960
TI  - Rosmarinus eriocalyx: An alternative to Rosmarinus officinalis as a source of
      antioxidant compounds.
AB  - Rosmarinus eriocalyx is an aromatic evergreen bush endemic to Algeria where it is
      used as a condiment to flavour soups and meat and as a traditional remedy. In the
      present work we have analyzed for the first time the phenolic composition of
      polar extracts obtained from stems, leaves and flowers of R. eriocalyx by HPLC,
      and determined the antioxidant and antimicrobial effects by DPPH, ABTS, FRAP,
      ORAC and agar disc diffusion methods, respectively. Results showed that ethanolic
      extracts of leaves and flowers are a rich source of phenolic compounds, mainly
      rosmarinic acid, carnosic acid and carnosol that are the main responsible for the
      noteworthy antioxidant activity observed in the assays. This study showed that R.
      eriocalyx might be a spice to be included in the European food additive list and
      used as a preservative agent besides R. officinalis.

PMID- 27719961
TI  - Establishing the relative importance of damaged starch and fructan as sources of
      fermentable sugars in wheat flour and whole meal bread dough fermentations.
AB  - It is generally believed that maltose drives yeast-mediated bread dough
      fermentation. The relative importance of fructose and glucose, released from
      wheat fructan and sucrose by invertase, compared to maltose is, however, not
      documented. This is surprising given the preference of yeast for glucose and
      fructose over maltose. This study revealed that, after 2h fermentation of wheat
      flour dough, about 44% of the sugars consumed were generated by invertase
      mediated degradation of fructan, raffinose and sucrose. The other 56% were
      generated by amylases. In whole meal dough, 70% of the sugars consumed were
      released by invertase activity. Invertase-mediated sugar release seems to be
      crucial during the first hour of fermentation, while amylase-mediated sugar
      release was predominant in the later stages of fermentation, which explains why
      higher amylolytic activity prolonged the productive fermentation time only. These
      results illustrate the importance of wheat fructan and sucrose content and their
      degradation for dough fermentations.

PMID- 27719962
TI  - Selective enzymatic hydrolysis of chlorogenic acid lactones in a model system and
      in a coffee extract. Application to reduction of coffee bitterness.
AB  - Chlorogenic acid lactones have been identified as key contributors to coffee
      bitterness. These compounds are formed during roasting by dehydration and
      cyclization of their precursors, the chlorogenic acids (CGAs). In the present
      study, we investigated an approach to decompose these lactones in a selective way
      without affecting the positive coffee attributes developed during roasting. A
      model system composed of (3-caffeoylquinic acid lactone (3-CQAL), 4- caffeoyl
      quinic acid lactone (4-CQAL), and 4-feruloylquinic acid lactone (4-FQAL)) was
      used for the screening of enzymes before treatment of the coffee extracts. Hog
      liver esterase (HLE) hydrolyzed chlorogenic acid lactones (CQALs, FQALs)
      selectively, while chlorogenate esterase hydrolyzed all chlorogenic acids (CQAs,
      FQAs) and their corresponding lactones (CQALs, FQALs) in a non-selective way.
      Enzymatically treated coffee samples were evaluated for their bitterness by a
      trained sensory panel and were found significantly less bitter than the untreated
      samples.

PMID- 27719964
TI  - XV International symposium on solid state dosimetry.

PMID- 27719963
TI  - A review of phenolic compounds in oil-bearing plants: Distribution,
      identification and occurrence of phenolic compounds.
AB  - Over the last two decades, separation, identification and measurement of the
      total and individual content of phenolic compounds has been widely investigated.
      Recently, the presence of a wide range of phenolic compounds in oil-bearing
      plants has been shown to contribute to their therapeutic properties, including
      anti-cancer, anti-viral, anti-oxidant, hypoglycemic, hypo-lipidemic, and anti
      inflammatory activities. Phenolics in oil-bearing plants are now recognized as
      important minor food components due to several organoleptic and health
      properties, and they are used as food or sources of food ingredients. Variations
      in the content of phenolics in oil-bearing plants have largely been attributed to
      several factors, including the cultivation, time of harvest and soil types. A
      number of authors have suggested that the presence phenolics in extracted
      proteins, carbohydrates and oils may contribute to objectionable off flavors The
      objective of this study was to review the distribution, identification and
      occurrence of free and bound phenolic compounds in oil-bearing plants.

PMID- 27719965
TI  - Special Issue: New Perspectives in PTSD.

PMID- 27719966
TI  - [Prevention and management of cognitive impairment].

PMID- 27719967
TI  - [Non-pharmacological treatment of cognitive impairment].
AB  - This article reviews the effect of non-pharmacological therapies in persons with
      cognitive impairment, especially treatments aimed at brain stimulation and
      functional maintenance, since both pharmacological and non-pharmacological
      therapies affecting the cognitive and psychoaffective domains are reviewed in
      another article in this supplement. The article also discusses the close and
      reciprocal relationship between cognitive impairment, diet and nutritional status
      and describes the main nutritional risk factors and protective factors in
      cognitive decline.

PMID- 27719968
TI  - [Pharmacological treatment].
AB  - Alzheimer's disease (AD) is a chronic degenerative and inflammatory process
      leading to synapticdysfunction and neuronal death. A review about the
      pharmacological treatment alternatives is made: acetylcholinesterase inhibitors
      (AChEI), a nutritional supplement (Souvenaid) and Ginkgo biloba. A special
      emphasis on Ginkgo biloba due to the controversy about its use and the approval
      by the European Medicines Agency is made.

PMID- 27719969
TI  - [Inflammation and oxidation: predictive and/or causative factors].
AB  - Brain ageing leads to a series of changes that reduce the processes of adaptation
      and response. These transformations can end in cognitive impairment and/or
      dementia. Although the cause of these changes is diverse, inflammation and
      oxidative stress explain some of the pathophysiological mechanisms of these
      anomalies of brain functioning. Neuroinflammation triggers neuronal injury
      through the presence of inflammatory cytokines and the activation of microglia
      through membrane receptors and nuclear activation factors. This neuroinflammatory
      phenomenon also affects neuron plasticity, altering the genesis and maintenance
      of long-term potentiation, leading to impairment of hippocampus-dependent memory.
      Oxidative stress and the production of free oxygen radicals also cause toxic
      effects in aged brains, largely due to lipid peroxidation and DNA damage. The
      identification of the molecular mechanisms involved in the pathogenesis of these
      events could shed new light on possible therapeutic targets and offer strategies
      for the prevention of diseases related to brain ageing, cognitive impairment and
      dementia.

PMID- 27719970
TI  - [Neurophysiology and ageing. Definition and pathophysiological foundations of
      cognitive impairment].
AB  - Brain ageing is produced by various morphological, biochemical, metabolic and
      circulatory changes, which are reflected in functional changes, whose impact
      depends on the presence or absence of cognitive impairment. Because of brain
      plasticity, together with redundancy of the distinct cerebral circuits, age-
      related deterioration of the brain at various levels does not always translate
      into loss of brain function. However, when the damage exceeds certain thresholds,
      there is age-related cognitive impairment, which increases the risk of developing
      various neurodegenerative diseases such as Alzheimer disease. Genetics, together
      with lifestyle, diet, and environmental factors, etc, can trigger the development
      of these diseases, which provoke cognitive impairment. This article discusses the
      most important age-related changes in the brain, as well as the
      pathophysiological foundations of cognitive impairment.

PMID- 27719971
TI  - [Prognosis and progression of cognitive impairment. Preventive measures].
AB  - Because of the substantial increase in population ageing, age-related processes,
      such as dementia and Alzheimer disease (AD), are becoming highly prevalent. The
      course of this disease, including preprodromic phases, lasts at least 20 years.
      The presence of comorbidities, especially those of vascular origin, can trigger
      and aggravate disease progression. On the other hand, cognitive reserve, the
      absence or control of comorbid factors and healthy lifestyles can protect or
      modify -in the sense of slow down- disease progression. Knowledge of the phases
      of AD and their functional impact on affected individuals helps to identify the
      average prognosis and, in particular, to establish and predict care plans based
      on the individual's needs.

PMID- 27719972
TI  - [Diagnostic criteria. Benefits of early diagnosis].
AB  - Almost 36 million persons live with dementia worldwide. This figure is set to
      double by 2030, with 66 million patients, and by 2050 there will be 116 million
      affected persons. Dementia has an economic impact on individuals and health
      services and affects the global economy. It is important to evaluate costs to
      plan social services and healthcare and to provide information on the cost
      effectiveness of treatments. The economic cost of dementia was around 604 billion
      dollars in 2010 and estimates are obviously set to rise.

PMID- 27719973
TI  - Imaging of Pulmonary Manifestations of Connective Tissue Diseases.
AB  - Connective tissue diseases (CTDs) are a heterogeneous group of conditions
      characterized by circulating autoantibodies and autoimmune-mediated organ damage.
      Common CTDs with lung manifestations are rheumatoid arthritis, scleroderma or
      systemic sclerosis, Sjogren syndrome, polymyositis/dermatomyositis, systemic
      lupus erythematosis, mixed connective tissue disease, and undifferentiated
      connective tissue disease. The most common histopathologic patterns of CTD
      related interstitial lung disease are nonspecific interstitial pneumonia, usual
      interstitial pneumonia, organizing pneumonia, and lymphoid interstitial
      pneumonia. Drug treatment of CTDs can cause complications, including
      opportunistic infection.

PMID- 27719974
TI  - Imaging of Hypersensitivity Pneumonitis.
AB  - The management of hypersensitivity pneumonitis (HP) depends on early
      identification of the disease process, which is complicated by its nonspecific
      clinical presentation in addition to variable and diverse laboratory and
      radiologic findings. HP is the result of exposure and sensitization to myriad
      aerosolized antigens. HP develops in the minority of antigenic exposures, and
      conversely has been documented in patients with no identifiable exposure,
      complicating the diagnostic algorithm significantly. Prompt diagnosis and early
      intervention are critical in slowing the progression of irreversible parenchymal
      damage, and additionally in preserving the quality of life of affected patients.

PMID- 27719975
TI  - Clinical-Radiologic-Pathologic Correlation of Smoking-Related Diffuse Parenchymal
      Lung Disease.
AB  - The direct toxicity of cigarette smoke and the body's subsequent response to this
      lung injury leads to a wide array of pathologic manifestations and disease states
      that lead to both reversible and irreversible injury to the large airways, small
      airways, alveolar walls, and alveolar spaces. These include emphysema,
      bronchitis, bronchiolitis, acute eosinophilic pneumonia, pulmonary Langerhans
      cell histiocytosis, respiratory bronchiolitis, desquamative interstitial
      pneumonia, and pulmonary fibrosis. Although these various forms of injury have
      different pathologic and imaging manifestations, they are all part of the
      spectrum of smoking-related diffuse parenchymal lung disease.

PMID- 27719976
TI  - Current Update on Interstitial Lung Disease of Infancy: New Classification
      System, Diagnostic Evaluation, Imaging Algorithms, Imaging Findings, and
      Prognosis.
AB  - Childhood interstitial lung disease represents a rare and heterogeneous group of
      diseases that can result in significant morbidity and mortality, some leading to
      death during infancy. CT is the imaging test of choice. Although many CT findings
      are nonspecific and a definitive diagnosis usually cannot be reached by CT alone,
      the interpreting radiologist is instrumental in defining disease extent and
      refining the diagnosis. Chest CTs are of key importance in guiding site selection
      for lung biopsy and for following disease progression and response to treatment.
      Thus, from the radiologist's perspective, ensuring maximal quality of CT imaging
      and interpretation is paramount.

PMID- 27719977
TI  - Imaging of Occupational Lung Disease.
AB  - Occupational lung diseases span a variety of pulmonary disorders caused by
      inhalation of dusts or chemical antigens in a vocational setting. Included in
      these are the classic mineral pneumoconioses of silicosis, coal worker's
      pneumoconiosis, and asbestos-related diseases as well as many immune-mediated and
      airway-centric diseases, and new and emerging disorders. Although some of these
      have characteristic imaging appearances, a multidisciplinary approach with focus
      on occupational exposure history is essential to proper diagnosis.

PMID- 27719978
TI  - Pulmonary Vasculitis: Spectrum of Imaging Appearances.
AB  - Pulmonary vasculitis is a relatively uncommon disorder, usually manifesting as
      part of systemic vasculitis. Imaging, specifically computed tomography, is often
      performed in the initial diagnostic workup. Although the findings in vasculitis
      can be nonspecific, they can provide important clues in the diagnosis, and guide
      the clinical team toward the right diagnosis. Radiologists must have knowledge of
      common and uncommon imaging findings in various vasculitides. Also, radiologists
      should be able to integrate the clinical presentation and laboratory test
      findings together with imaging features, so as to provide a meaningful
      differential diagnosis.

PMID- 27719979
TI  - Imaging of Acute Lung Injury.
AB  - Acute lung injury (ALI) is the clinical syndrome associated with histopathologic
      diffuse alveolar damage. It is a common cause of acute respiratory symptoms and
      admission to the intensive care unit. Diagnosis of ALI is typically based on
      clinical and radiographic criteria; however, because these criteria can be
      nonspecific, diagnostic uncertainty is common. A multidisciplinary approach that
      synthesizes clinical, imaging, and pathologic data can ensure an accurate
      diagnosis. Radiologists must be aware of the radiographic and computed
      tomographic findings of ALI and its mimics. This article discusses the
      multidisciplinary diagnosis of ALI from the perspective of the imager.

PMID- 27719980
TI  - Imaging of Pulmonary Hypertension.
AB  - Multimodality, noninvasive imaging is increasingly used in the identification and
      management of pulmonary hypertension (PH). Chest radiography, ventilation
      perfusion scintigraphy, and Doppler echocardiography are frequently the initial
      studies used to evaluate patients suspected of having PH. However, their ability
      to evaluate the right ventricle (RV) and pulmonary vasculature is limited.
      Computed tomography (CT) and magnetic resonance (MR) imaging are increasingly
      used to identify causes of PH and assess the effect of PH on RV function. This
      article describes the noninvasive imaging techniques and findings, particularly
      CT and MR imaging, used in the diagnosis and management of suspected or known PH.

PMID- 27719981
TI  - Imaging of Eosinophilic Lung Diseases.
AB  - Eosinophilic lung diseases encompass a broad range of conditions wherein patients
      present with pulmonary opacities and eosinophilia of the serum, pulmonary tissue,
      or bronchoalveolar lavage fluid. Many of these entities can be idiopathic or are
      secondary to parasitic infection, exposure to drugs, toxins, or radiation. These
      diseases exhibit a wide range of imaging findings, including consolidation,
      ground-glass opacities, nodules, and masses. Diagnoses often require
      bronchoalveolar lavage and/or biopsy to confirm respiratory eosinophilia and to
      exclude other entities, such as infection or malignancy. Treatment entails
      administration of corticosteroids, removal of inciting agents, and treatment of
      underlying infection.

PMID- 27719982
TI  - Imaging of Small Airways Diseases.
AB  - Small airways disease, or bronchiolitis, encompasses many conditions that result
      in bronchiolar inflammation and/or fibrosis. Bronchioles are distal airways
      within secondary pulmonary lobules that are only visible on imaging when
      abnormal. High-resolution computed tomography plays an important role in
      diagnosing small airways disease. The predominant direct high-resolution computed
      tomography sign of bronchiolitis includes centrilobular nodules, whereas air
      trapping is the main indirect finding. This article reviews bronchiolar anatomy,
      discusses the differential diagnosis for cellular and constrictive bronchiolitis
      with a focus on key imaging features, and discusses how to distinguish important
      mimics.

PMID- 27719983
TI  - Imaging of Diseases of the Large Airways.
AB  - Imaging of the large airways is key to the diagnosis and management of a wide
      variety of congenital, infectious, malignant, and inflammatory diseases.
      Involvement can be focal, regional, or diffuse, and abnormalities can take the
      form of masses, thickening, narrowing, enlargement, or a combination of patterns.
      Recognition of the typical morphologies, locations, and distributions of large
      airways disease is central to an accurate imaging differential diagnosis.

PMID- 27719984
TI  - Imaging of Idiopathic Pulmonary Fibrosis.
AB  - Idiopathic interstitial pneumonias are a heterogeneous group of diffuse lung
      diseases characterized by distinct clinicopathologic entities with the usual
      interstitial pneumonia (UIP) being the most common. The pattern of UIP can be
      seen in idiopathic pulmonary fibrosis (IPF) as well as in secondary causes, most
      commonly in connective tissue diseases. IPF is usually progressive and associated
      with a very poor prognosis, and newer therapies pose a risk of serious
      complications; therefore, diagnostic certainty is crucial. This article reviews
      the radiologic findings in UIP with clinical correlation and histopathologic
      features along with its significance for prognosis and patients monitoring.

PMID- 27719985
TI  - Diffuse White Stuff in the Lungs: Challenges and Advances.

PMID- 27719986
TI  - Epidemiology of Childhood and Adult Mental Illness.
AB  - The global burden of adult neuropsychiatric illness and childhood mental
      disorders is enormous, accounting for a significant burden of disability in
      adults and a major factor of overall health that continues throughout the
      lifespan of children and into adulthood.

PMID- 27719987
TI  - Childhood Vaccination: Implications for Global and Domestic Public Health.
AB  - The role of vaccination in the control and prevention of endemic and emerging
      diseases cannot be overemphasized. Induction of host protective immunity may be
      the most powerful tool and effective strategy in preventing the spread of
      potentially fatal disease and emerging illnesses, in particular in susceptible
      immunologically naive hosts. The strategy for vaccination programs is engrained
      in population studies recognizing benefit for the health and economic welfare of
      at-risk indigenous populations. Worldwide collaboration is a necessary aspect of
      vaccine-preventable diseases recognizing that even a small number of wild-type
      cases of an eradicated disease in one region presents opportunities for re
      emergence of the disease in geographically remote areas.

PMID- 27719988
TI  - Epidemiology of Zika Virus.
AB  - Zika virus is an arbovirus belonging to the Flaviviridae family known to cause
      mild clinical symptoms similar to those of dengue and chikungunya. Zika is
      transmitted by different species of Aedes mosquitoes. Nonhuman primates and
      possibly rodents play a role as reservoirs. Direct interhuman transmission has
      also been reported. Human cases have been reported in Africa and Asia, Easter
      Island, the insular Pacific region, and Brazil. Its clinical profile is that of a
      dengue-like febrile illness, but recently associated Guillain-Barre syndrome and
      microcephaly have appeared. There is neither a vaccine nor prophylactic
      medications available to prevent Zika virus infection.

PMID- 27719989
TI  - Assessing the Public's Health.
AB  - Metrics are an important part of the assessment of public health. They include
      traditional measures of mortality and newly described summary measures to
      describe the disability engendered by diseases. Epidemiology has transformed the
      understanding of risk factors for disease; however, a holistic approach includes
      recognition of social determinants and the neighborhood and communities where the
      people most at risk reside.

PMID- 27719990
TI  - Health Care in Brazil: Implications for Public Health and Epidemiology.
AB  - A network of family-based community-oriented primary health programs, or Programa
      Agentes Communitarios de Saude, and family health programs, or Programa Saude da
      Familia, introduced almost 2 decades ago were the Brazilian government's health
      care models to restructure primary care under the Unified Health System, or
      Sistema Unico de Saude. The latter offers comprehensive coverage to all, although
      it is used by those of lower income, and despite achievement in the last quarter
      century, access to health services and gradients of health status continue to
      persist along income, educational background, racial, and religious lines.

PMID- 27719991
TI  - Health Care in the Russian Federation.
AB  - The Russian Federation health system has its roots in the country's complex
      political history. The Ministry of Health and Social Development and its
      associated federal services are the principal Russian institutions subserving the
      Russian Federation. Funding for the health system goes through 2 channels: the
      general revenue budget managed by federal, regional, and local health
      authorities, and the Mandatory Health Insurance Fund. Although the Soviet Union
      was the first country in the world to guarantee free medical care as a
      constitutional right to all its citizens, quality and accessibility are in
      question.

PMID- 27719992
TI  - Health Care in India.
AB  - Although a stated right for all Indians, equal access to health care in India is
      impeded by socioeconomic barriers. With its 3-tier system of public health care
      centers in villages, district hospitals, and tertiary care hospitals, government
      expenditure in India is inordinately low, with a disproportionate emphasis on
      private health spending. Accordingly, the poorest receive a minority of the
      available subsidies, whereas the richest obtain more than a third, fostering a
      divide in health care infrastructure across the rich and poor in urban and rural
      settings. This paradigm has implications for domestic Indian public health and
      global public health.

PMID- 27719993
TI  - Health Care in China.
AB  - China has recently emerged as an important global partner. However, like other
      developing nations, China has experienced dramatic demographic and epidemiologic
      changes in the past few decades. Population discontent with the health care
      system has led to major reforms. China's distinctive health care system,
      including its unique history, vast infrastructure, the speed of health reform,
      and economic capacity to make important advances in health care, nonetheless, has
      incomplete insurance coverage for urban and rural dwellers, uneven access, mixed
      quality of health care, increasing costs, and risk of catastrophic health
      expenditures.

PMID- 27719994
TI  - Health Care in South Africa.
AB  - The South African health care system is embedded in a background of racial
      subordination and sexual violence against girls and women and of hierarchical
      male authority from youth to adulthood. Low wages, unemployment, urban
      overcrowding, inadequate sanitation, malnutrition, crime, and violence have
      contributed to economic and health inequality. With more health-insured whites
      than blacks and the proportion of gross national product spent on health care
      slowly increasing, two-thirds of health expenditures have been consumed by the
      private sector at a time when the cost of health insurance has risen to more than
      3 times the rate of the consumer price index.

PMID- 27719995
TI  - Research Methods in Epidemiology.
AB  - Epidemiology is the study of the distribution and determinants of health-related
      states and in specified populations and the application to control health
      problems. Classified as either descriptive or analytical, a variety of
      epidemiologic approaches can be used to allow assessment of hypothesized risk
      factor exposure with disease outcomes. This article reviews salient aspects of
      epidemiologic research methods that are used repeatedly in articles in this
      volume on public health, neuroepidemiology, and health systems.

PMID- 27719996
TI  - The Epidemiology of Global Epilepsy.
AB  - The International League Against Epilepsy defines epilepsy as at least 2
      unprovoked seizures more than 24 hours apart. It is a wide-reaching and complex
      illness affecting more than 70 million people worldwide and can take on a variety
      of forms, patterns, and severities. Geographic differences in the illness are
      often related to its etiology. A host of endemic illnesses and parasitic
      infections can lead to epilepsy syndromes. Management varies by region due to the
      availability of diagnostic modalities and medications. Treatment gaps in epilepsy
      care often are related to social and cultural factors that must also be
      understood.

PMID- 27719997
TI  - Epidemiology of Migraine.
AB  - Headache disorders cause significant disability. The public and most health
      professionals tend to perceive migraine as a minor or trivial complaint. In the
      past decade, important epidemiologic studies enjoining extensive surveys,
      pathophysiologic and genetic insights, and revised headache classification
      paradigms have produced clear evidence of the public health importance of
      headache disorders. The Global Campaign to reduce the burden of headache
      worldwide known as "Lifting the Burden" was launched in 2004 by the World Health
      Organization, the International Headache Society, the World Headache Alliance,
      and the European Headache Federation. This paper reviews salient progress in the
      neuroepidemiology of migraine headaches.

PMID- 27719998
TI  - I-Cubed (Infection, Immunity, and Inflammation) and the Human Microbiome.
AB  - Medical science is just now realizing the full importance of the microbial world.
      Thanks to developments such as low-cost high-throughput sequencing of microbial
      communities comprising the human microbiome, the identity and function of
      unculturable microbes are being unveiled. Public health officials and
      neuroepidemiology researchers will be called on to guide the understanding of I
      Cubed illnesses and the implications of the human microbiome for communicable and
      noncommunicable diseases, as the natural history is appreciated and the
      responsiveness of given medical and neurologic disorders to a variety of medical
      approaches, including strong antibiotics and immune-modulatory therapy is
      established.

PMID- 27719999
TI  - Epidemiology of Lyme Neuroborreliosis.
AB  - Lyme disease is caused by the bacterium Borrelia burgdorferi and is transmitted
      to humans through the bite of infected blacklegged ticks. According to the
      Centers for Disease Control and Prevention, it is the most commonly reported
      vector-borne illness and the fifth most common disease in the National Notifiable
      Diseases Surveillance System. If left untreated, infection disseminates to the
      nervous system. The nonhuman primate model of Lyme disease of the nervous system,
      or Lyme neuroborreliosis, accurately mimics the aspects of the human illness.
      There is general recognition for the potential of infectious-related autoimmune
      inflammatory processes contributing to disease progression and clinical
      manifestations.

PMID- 27720000
TI  - Epidemiology of Neurovasculitis.
AB  - The epidemiology of vasculitis has witnessed extraordinary advances in the past
      decade influenced by the worldwide increased recognition and accurate
      classification and diagnosis of the vasculitides, and insights brought by genome
      wide association studies and other genetic investigations that contribute to the
      understanding of the heritable factors of some of the disorders. This article
      reviews the current knowledge of the epidemiology of vasculitides in different
      global regions.

PMID- 27720001
TI  - Epidemiology of Multiple Sclerosis.
AB  - The epidemiology of multiple sclerosis (MS) includes a consideration of genetic
      and environmental factors. Comparative studies of different populations have
      revealed prevalence and incidence rates that vary with geography and ethnicity.
      With a prevalence ranging from 2 per 100,000 in Japan to greater than 100 per
      100,000 in Northern Europe and North America, the burden of MS is similarly
      unevenly influenced by longevity and comorbid disorders. Well-powered genome-wide
      association studies have investigated the genetic substrate of MS, providing
      insight into autoimmune mechanisms involved in the etiopathogenesis of MS and
      elucidating possible avenues of biological treatment.

PMID- 27720003
TI  - Epidemiology of Parkinson Disease.
AB  - Parkinson disease (PD) is a common progressive neurodegenerative condition,
      causing both motor and non motor symptoms. Motor symptoms include stiffness,
      slowness, rest tremor and poor postural reflexes, whereas nonmotor symptoms
      include abnormalities of mood, cognition, sleep and autonomic function. Affected
      patients show cell loss in the substantia nigra pars compacta, and accumulation
      of aggregated alpha-synuclein into intracellular structures called Lewy bodies,
      within specific brain regions. The main known non modifiable risk factor is age.
      The neuroepidemiology of PD is complex with susceptibility genes and a number of
      modifiable risk factors that can increase and others that can mitigate risk and
      outcome.

PMID- 27720004
TI  - Epidemiology of Ischemic Stroke.
AB  - Ischemic stroke is a heterogeneous multifactorial disorder recognized by the
      sudden onset of neurologic signs related directly to the sites of injury in the
      brain where the morbid process occurs. The evaluation of complex neurologic
      disorders, such as stroke, in which multiple genetic and epigenetic factors
      interact with environmental risk factors to increase the risk has been
      revolutionized by the genome-wide association studies (GWAS) approach. This
      article reviews salient aspects of ischemic stroke emphasizing the impact of
      neuroepidemiology and GWAS.

PMID- 27720005
TI  - Epidemiology of Brain Tumors.
AB  - Brain tumors are the commonest solid tumor in children, leading to significant
      cancer-related mortality. Several hereditary syndromes associated with brain
      tumors are nonfamilial. Ionizing radiation is a well-recognized risk factor for
      brain tumors. Several industrial exposures have been evaluated for a causal
      association with brain tumor formation but the results are inconclusive. A casual
      association between the common mutagens of tobacco, alcohol, or dietary factors
      has not yet been established. There is no clear evidence that the incidence of
      brain tumors has changed over time. This article presents the descriptive
      epidemiology of the commonest brain tumors of children and adults.

PMID- 27720008
TI  - Erratum.

PMID- 27720002
TI  - Alzheimer Disease and Its Growing Epidemic: Risk Factors, Biomarkers, and the
      Urgent Need for Therapeutics.
AB  - Alzheimer disease (AD) represents one of the greatest medical challenges of this
      century; the condition is becoming increasingly prevalent worldwide and no
      effective treatments have been developed for this terminal disease. Because the
      disease manifests at a late stage after a long period of clinically silent
      neurodegeneration, knowledge of the modifiable risk factors and the
      implementation of biomarkers is crucial in the primary prevention of the disease
      and presymptomatic detection of AD, respectively. This article discusses the
      growing epidemic of AD and antecedent risk factors in the disease process.
      Disease biomarkers are discussed, and the implications that this may have for the
      treatment of this currently incurable disease.

PMID- 27720006
TI  - The Epidemiology of Neuromuscular Diseases.
AB  - Neuromuscular disorders as a group are linked by anatomy with significant
      differences in pathogenetic mechanisms, clinical expression, and time course of
      disease. Each neuromuscular disease is relatively uncommon, yet causes a
      significant burden of disease socioeconomically. Epidemiologic studies in
      different global regions have demonstrated certain neuromuscular diseases have
      increased incidence and prevalence rates over time. Understanding differences in
      global epidemiologic trends will aid clinical research and policies focused on
      prevention of disease. There is a critical need to understand the global impact
      of neuromuscular diseases using metrics currently established for communicable
      and noncommunicable diseases.

PMID- 27720009
TI  - The Journey of Lipoproteins Through the Cell: One Birthplace, Multiple
      Destinations.
AB  - Bacterial lipoproteins are a very diverse group of proteins characterized by the
      presence of an N-terminal lipid moiety that serves as a membrane anchor.
      Lipoproteins have a wide variety of crucial functions, ranging from envelope
      biogenesis to stress response. In Gram-negative bacteria, lipoproteins can be
      targeted to various destinations in the cell, including the periplasmic side of
      the cytoplasmic or outer membrane, the cell surface or the external milieu. The
      sorting mechanisms have been studied in detail in Escherichia coli, but
      exceptions to the rules established in this model bacterium exist in other
      bacteria. In this chapter, we will present the current knowledge on lipoprotein
      sorting in the cell. Our particular focus will be on the surface-exposed
      lipoproteins that appear to be much more common than previously assumed. We will
      discuss the different targeting strategies, provide numerous examples of surface
      exposed lipoproteins and discuss the techniques used to assess their surface
      exposure.

PMID- 27720011
TI  - Polar Marine Microorganisms and Climate Change.
AB  - The large diversity of marine microorganisms harboured by oceans plays an
      important role in planet sustainability by driving globally important
      biogeochemical cycles; all primary and most secondary production in the oceans is
      performed by microorganisms. The largest part of the planet is covered by cold
      environments; consequently, cold-adapted microorganisms have crucial functional
      roles in globally important environmental processes and biogeochemical cycles
      cold-adapted extremophiles are a remarkable model to shed light on the molecular
      basis of survival at low temperature. The indigenous populations of Antarctic and
      Arctic microorganisms are endowed with genetic and physiological traits that
      allow them to live and effectively compete at the temperatures prevailing in
      polar regions. Some genes, e.g. glycosyltransferases and glycosylsynthetases
      involved in the architecture of the cell wall, may have been acquired/retained
      during evolution of polar strains or lost in tropical strains. This present work
      focusses on temperature and its role in shaping microbial adaptations; however,
      in assessing the impacts of climate changes on microbial diversity and
      biogeochemical cycles in polar oceans, it should not be forgotten that
      physiological studies need to include the interaction of temperature with other
      abiotic and biotic factors.

PMID- 27720010
TI  - The Impact of Gene Silencing on Horizontal Gene Transfer and Bacterial Evolution.
AB  - The H-NS family of DNA-binding proteins is the subject of intense study due to
      its important roles in the regulation of horizontally acquired genes critical for
      virulence, antibiotic resistance, and metabolism. Xenogeneic silencing proteins,
      typified by the H-NS protein of Escherichia coli, specifically target and
      downregulate expression from AT-rich genes by selectively recognizing specific
      structural features unique to the AT-rich minor groove. In doing so, these
      proteins facilitate bacterial evolution; enabling these cells to engage in
      horizontal gene transfer while buffering potential any detrimental fitness
      consequences that may result from it. Xenogeneic silencing and counter-silencing
      explain how bacterial cells can evolve effective gene regulatory strategies in
      the face of rampant gene gain and loss and it has extended our understanding of
      bacterial gene regulation beyond the classic operon model. Here we review the
      structures and mechanisms of xenogeneic silencers as well as their impact on
      bacterial evolution. Several H-NS-like proteins appear to play a role in
      facilitating gene transfer by other mechanisms including by regulating
      transposition, conjugation, and participating in the activation of virulence loci
      like the locus of enterocyte effacement pathogenicity island of pathogenic
      strains of E. coli. Evidence suggests that the critical determinants that dictate
      whether an H-NS-like protein will be a silencer or will perform a different
      function do not lie in the DNA-binding domain but, rather, in the domains that
      control oligomerization. This suggests that H-NS-like proteins are transcription
      factors that both recognize and alter the shape of DNA to exert specific effects
      that include but are not limited to gene silencing.

PMID- 27720013
TI  - Preface.

PMID- 27720012
TI  - The Making and Taking of Lipids: The Role of Bacterial Lipid Synthesis and the
      Harnessing of Host Lipids in Bacterial Pathogenesis.
AB  - In order to survive environmental stressors, including those induced by growth in
      the human host, bacterial pathogens will adjust their membrane physiology
      accordingly. These physiological changes also include the use of host-derived
      lipids to alter their own membranes and feed central metabolic pathways. Within
      the host, the pathogen is exposed to many stressful stimuli. A resulting
      adaptation is for pathogens to scavenge the host environment for readily
      available lipid sources. The pathogen takes advantage of these host-derived
      lipids to increase or decrease the rigidity of their own membranes, to provide
      themselves with valuable precursors to feed central metabolic pathways, or to
      impact host signalling and processes. Within, we review the diverse mechanisms
      that both extracellular and intracellular pathogens employ to alter their own
      membranes as well as their use of host-derived lipids in membrane synthesis and
      modification, in order to increase survival and perpetuate disease within the
      human host. Furthermore, we discuss how pathogen employed mechanistic utilization
      of host-derived lipids allows for their persistence, survival and potentiation of
      disease. A more thorough understanding of all of these mechanisms will have
      direct consequences for the development of new therapeutics, and specifically,
      therapeutics that target pathogens, while preserving normal flora.

PMID- 27720014
TI  - Corrigendum to "Five new fawcettimine-related alkaloids from Lycopodium japoniucm
      Thunb." [Fitoterapia (2013) 74 -81].

PMID- 27720016
TI  - Asthma phenotypes in inner-city children.
AB  - BACKGROUND: Children with asthma in low-income urban areas have high morbidity.
      Phenotypic analysis in these children is lacking, but may identify
      characteristics to inform successful tailored management approaches. OBJECTIVE:
      We sought to identify distinct asthma phenotypes among inner-city children
      receiving guidelines-based management. METHODS: Nine inner-city asthma consortium
      centers enrolled 717 children aged 6 to 17 years. Data were collected at baseline
      and prospectively every 2 months for 1 year. Participants' asthma and rhinitis
      were optimally managed by study physicians on the basis of guidelines. Cluster
      analysis using 50 baseline and 12 longitudinal variables was performed in 616
      participants completing 4 or more follow-up visits. RESULTS: Five clusters
      (designated A through E) were distinguished by indicators of asthma and rhinitis
      severity, pulmonary physiology, allergy (sensitization and total serum IgE), and
      allergic inflammation. In comparison to other clusters, cluster A was
      distinguished by lower allergy/inflammation, minimally symptomatic asthma and
      rhinitis, and normal pulmonary physiology. Cluster B had highly symptomatic
      asthma despite high step-level treatment, lower allergy and inflammation, and
      mildly altered pulmonary physiology. Cluster C had minimally symptomatic asthma
      and rhinitis, intermediate allergy and inflammation, and mildly impaired
      pulmonary physiology. Clusters D and E exhibited progressively higher asthma and
      rhinitis symptoms and allergy/inflammation. Cluster E had the most symptomatic
      asthma while receiving high step-level treatment and had the highest total serum
      IgE level (median, 733 kU/L), blood eosinophil count (median, 400 cells/mm3), and
      allergen sensitizations (15 of 22 tested). CONCLUSIONS: Allergy distinguishes
      asthma phenotypes in urban children. Severe asthma often coclusters with highly
      allergic children. However, a symptomatic phenotype with little allergy or
      allergic inflammation was identified.

PMID- 27720017
TI  - Distinguishing characteristics of difficult-to-control asthma in inner-city
      children and adolescents.
AB  - BACKGROUND: Treatment levels required to control asthma vary greatly across a
      population with asthma. The factors that contribute to variability in treatment
      requirements of inner-city children have not been fully elucidated. OBJECTIVE: We
      sought to identify the clinical characteristics that distinguish difficult-to
      control asthma from easy-to-control asthma. METHODS: Asthmatic children aged 6 to
      17 years underwent baseline assessment and bimonthly guideline-based management
      visits over 1 year. Difficult-to-control and easy-to-control asthma were defined
      as daily therapy with 500 MUg of fluticasone or greater with or without a long
      acting beta-agonist versus 100 MUg or less assigned on at least 4 visits. Forty
      four baseline variables were used to compare the 2 groups by using univariate
      analyses and to identify the most relevant features of difficult-to-control
      asthma by using a variable selection algorithm. Nonlinear seasonal variation in
      longitudinal measures (symptoms, pulmonary physiology, and exacerbations) was
      examined by using generalized additive mixed-effects models. RESULTS: Among 619
      recruited participants, 40.9% had difficult-to-control asthma, 37.5% had easy-to
      control asthma, and 21.6% fell into neither group. At baseline, FEV1
      bronchodilator responsiveness was the most important characteristic
      distinguishing difficult-to-control asthma from easy-to-control asthma. Markers
      of rhinitis severity and atopy were among the other major discriminating
      features. Over time, difficult-to-control asthma was characterized by high
      exacerbation rates, particularly in spring and fall; greater daytime and
      nighttime symptoms, especially in fall and winter; and compromised pulmonary
      physiology despite ongoing high-dose controller therapy. CONCLUSIONS: Despite
      good adherence, difficult-to-control asthma showed little improvement in
      symptoms, exacerbations, or pulmonary physiology over the year. In addition to
      pulmonary physiology measures, rhinitis severity and atopy were associated with
      high-dose asthma controller therapy requirement.

PMID- 27720019
TI  - Pharmacogenomics and adverse drug reactions: Primetime and not ready for
      primetime tests.
AB  - Adverse drug reactions (ADRs) are a relatively common cause of morbidity and
      mortality. Many factors can contribute to ADRs, including genetics. The degree to
      which genetics contributes to ADRs is not entirely clear and varies by drug, as
      well as the type of ADR. Pharmacogenetics and, more recently, pharmacogenomics
      have been applied to the field of ADRs for both predictable ADRs and
      hypersensitivity drug reactions. Evaluations for glucose-6-phosphate
      dehydrogenase and thiopurine S-methyltransferase are commonplace clinical tests
      to reduce hematologic problems associated with drugs, such as dapsone and
      azathioprine, respectively. Numerous pharmacogenetic associations have been
      discovered for immediate hypersensitivity reactions to beta-lactams, aspirin, and
      nonsteroidal anti-inflammatory drugs; however, the clinical utility of testing
      for these genetic associations has not been established. In contrast,
      pharmacogenetic testing for HLA-B*1502 before carbamazepine in patients of
      certain Asian ethnicities and testing for HLA-B*5701 before abacavir treatment
      are recommended. This review will focus on pharmacogenetics and pharmacogenomics
      and their role in reducing ADRs, especially those caused by drug hypersensitivity
      reactions.

PMID- 27720018
TI  - Pathways through which asthma risk factors contribute to asthma severity in inner
      city children.
AB  - BACKGROUND: Pathway analyses can be used to determine how host and environmental
      factors contribute to asthma severity. OBJECTIVE: To investigate pathways
      explaining asthma severity in inner-city children. METHODS: On the basis of
      medical evidence in the published literature, we developed a conceptual model to
      describe how 8 risk-factor domains (allergen sensitization, allergic
      inflammation, pulmonary physiology, stress, obesity, vitamin D, environmental
      tobacco smoke [ETS] exposure, and rhinitis severity) are linked to asthma
      severity. To estimate the relative magnitude and significance of hypothesized
      relationships among these domains and asthma severity, we applied a causal
      network analysis to test our model in an Inner-City Asthma Consortium study.
      Participants comprised 6- to 17-year-old children (n = 561) with asthma and
      rhinitis from 9 US inner cities who were evaluated every 2 months for 1 year.
      Asthma severity was measured by a longitudinal composite assessment of day and
      night symptoms, exacerbations, and controller usage. RESULTS: Our conceptual
      model explained 53.4% of the variance in asthma severity. An allergy pathway
      (linking allergen sensitization, allergic inflammation, pulmonary physiology, and
      rhinitis severity domains to asthma severity) and the ETS exposure pathway
      (linking ETS exposure and pulmonary physiology domains to asthma severity)
      exerted significant effects on asthma severity. Among the domains, pulmonary
      physiology and rhinitis severity had the largest significant standardized total
      effects on asthma severity (-0.51 and 0.48, respectively), followed by ETS
      exposure (0.30) and allergic inflammation (0.22). Although vitamin D had modest
      but significant indirect effects on asthma severity, its total effect was
      insignificant (0.01). CONCLUSIONS: The standardized effect sizes generated by a
      causal network analysis quantify the relative contributions of different domains
      and can be used to prioritize interventions to address asthma severity.

PMID- 27720021
TI  - [Cutaneous leishmaniasis caused by Leishmania infantum: A limited therapeutic
      arsenal against extensive clinical polymorphism].

PMID- 27720022
TI  - Lifetime effects of infection with bovine leukemia virus on longevity and milk
      production of dairy cows.
AB  - Enzootic bovine leukosis (EBL) is an economically important disease of dairy
      cattle caused by bovine leukemia virus (BLV). The economic impacts of the
      infection have been debated in the literature. The present study was conducted to
      determine the lifetime effects of BLV infection on longevity and milk production
      of dairy cows in Canada. The data were aggregated from a combination of two data
      sets: 1) BLV serum-ELISA test results from Canada-wide surveys of production
      limiting diseases, which took place between 1998 and 2003 in 8 provinces, and 2)
      longitudinal production data for all cows in the former study, extracted from the
      Canadian dairy herd improvement database. All participant cows had been culled or
      died by the onset of this study. A historical cohort study was designed,
      including cows which tested positive to BLV-antibodies in their first lactation
      (positive cohort, n=1858) and cows which tested negative in their second or later
      lactations (negative cohort, n=2194). To assess the impacts of infection with BLV
      on longevity (the number of lifetime lactations), a discrete-time survival
      analysis was carried out. The effect of BLV on the lifetime milk production (the
      sum of all life 305-day milk production) was evaluated using a multilevel linear
      regression model. Overall, 4052 cows from 348 herds met the eligibility criteria
      and were enrolled in the study. In the longevity model, the interaction term
      between time (lactation number) and BLV-status was highly significant. Cows which
      were positive to BLV had consistently greater probabilities of being culled (or
      dying) than the test-negative cows. In the milk production model, the interaction
      term between BLV-status and longevity of the cows was highly significant;
      indicating that lifetime BLV effects on the total milk production was dependent
      on the lactation in which the study cows were culled/died. Infected cows with 2
      and 3 lactations showed significantly lower life milk productions [-2554kg (-3609
      to -1500) and -1171kg (-2051 to -292), respectively] compared with their negative
      counterparts with 2 and 3 lactations. As the cows lived longer (>3 lactations),
      the differences in life milk production between the two cohorts were no longer
      significant. Overall, it was predicted that the test-positive cows produced
      substantially lower milk compared to the test-negative cows throughout their
      study lifespans. With the high prevalence of BLV in Canadian dairy cows and its
      detrimental economic impacts, pursuing broad-based control programs in Canada
      should be evaluated.

PMID- 27720020
TI  - Exome and genome sequencing for inborn errors of immunity.
AB  - The advent of next-generation sequencing (NGS) in 2010 has transformed medicine,
      particularly the growing field of inborn errors of immunity. NGS has facilitated
      the discovery of novel disease-causing genes and the genetic diagnosis of
      patients with monogenic inborn errors of immunity. Whole-exome sequencing (WES)
      is presently the most cost-effective approach for research and diagnostics,
      although whole-genome sequencing offers several advantages. The scientific or
      diagnostic challenge consists in selecting 1 or 2 candidate variants among
      thousands of NGS calls. Variant- and gene-level computational methods, as well as
      immunologic hypotheses, can help narrow down this genome-wide search. The key to
      success is a well-informed genetic hypothesis on 3 key aspects: mode of
      inheritance, clinical penetrance, and genetic heterogeneity of the condition.
      This determines the search strategy and selection criteria for candidate alleles.
      Subsequent functional validation of the disease-causing effect of the candidate
      variant is critical. Even the most up-to-date dry lab cannot clinch this
      validation without a seasoned wet lab. The multifariousness of variations entails
      an experimental rigor even greater than traditional Sanger sequencing-based
      approaches in order not to assign a condition to an irrelevant variant. Finding
      the needle in the haystack takes patience, prudence, and discernment.

PMID- 27720023
TI  - Perceptions of French private veterinary practitioners' on their role in organic
      dairy farms and opportunities to improve their advisory services for organic
      dairy farmers.
AB  - Veterinarians could be the expected sparring partners of organic dairy farmers in
      promoting animal health which is one of the main organic principles. However, in
      the past organic dairy farmers did not always consider veterinarians to be
      pertinent advisors for them. The objectives of this study are - from private
      veterinary practitioners' point of views- i) to describe the roles of
      veterinarians today in organic dairy farmers' animal health promotion strategies,
      ii) to identify factors related to organic farming which determine their role on
      organic dairy farms, and, iii) to identify opportunities for improvement of
      veterinarians' advisory services for organic dairy herds. Fourteen veterinarians,
      providing herd health advisory services to dairy farmers, were interviewed using
      qualitative semi-structured research interviews. A modified approach to Grounded
      Theory was used for data collection and analysis. Most often veterinarians had
      only contact with the organic dairy farmers in cases of individual ill animals or
      acute herd health problems. Even though certain veterinarians experienced
      situations and approaches of animal health and welfare on organic dairy farms not
      meeting their standards, they were not always able to establish themselves an
      advisory role supporting farmers in improving this. Indeed, organic production
      principles, regulations and farmers' health approaches challenged veterinarians'
      values on animal health and welfare and their perceptions of 'good veterinary
      practices'. Also, some veterinarians considered that there was no direct economic
      interest for them in the organic dairy sector and that could diminish their
      willingness to invest in this sector. Possible opportunities for improvement were
      identified; for example proposing more proactively advice via existing
      organisations, by making adaptations to advisory services for the organic sector
      and/or by dissociating veterinarians' curative role from their advisory role in
      disease prevention.

PMID- 27720024
TI  - Changes in perceptions and motivators that influence the implementation of on
      farm Salmonella control measures by pig farmers in England.
AB  - This study presents British farmers' perception of, and barriers to, implementing
      Salmonella control on pig farms. Four farms that had implemented interventions
      and their 33 close contacts (known to the intervention farmers) took part in
      interviews before (phase 1) and after (phase 2) intervention trials to assess the
      difference in perception over time. Their results were compared against those
      from nine randomly selected control farms. The hypothesis was that farms
      implementing interventions whether or not successful, would influence their close
      contacts' opinion over time. Based on a 'pathway to disease control' model, three
      intrinsic factors known to influence motivation - attitudes, social norms and
      self-efficacy - were evaluated. Farmers mentioned that successful interventions
      on a farm would attract their attention. The use of an appropriate communication
      strategy is therefore recommended to stimulate farmers' intent to implement
      control measures. Both before and after the intervention trials, all farmers had
      a positive attitude towards Salmonella control and felt that their peers and
      authorities were supportive of controlling Salmonella on farms. In phase 2,
      however, farmers were more likely to want to share the burden of control with
      other stakeholders along the food chain and their belief in self-efficacy had
      weakened. Whilst social norms were not associated with an intention to take
      action on control, a positive attitude towards Salmonella control and a belief in
      self-efficacy were more likely to result in an intent to control. In phase 2,
      farmers with an intent to implement an intervention appeared to have a greater,
      but not significant positive belief in self-efficacy (p=0.108). This study
      confirmed that farmers recognised their responsibility for controlling Salmonella
      in pork - even though their confidence in their ability to control Salmonella
      decreased over time - and believed that responsibility should be shared with the
      rest of the production chain. It showed that farmers trusted their veterinarian
      as a source of advice to guide them during the process of implementing change,
      though an increase in farms' Salmonella seroprevalence score (Zoonosis National
      Control Programme (ZNCP) score) especially for those with a low ZNCP score was
      also likely to influence their behaviour. Getting concrete feedback from
      customers or a tangible benefit from their action was a strong incentive
      especially for farms with a ZNCP score higher than 50%. The study also revealed a
      need to validate which measures are effective as farmers did not perceive that
      the current advised interventions were worth the additional effort.

PMID- 27720025
TI  - Evaluating the efficacy of regionalisation in limiting high-risk livestock trade
      movements.
AB  - Many countries implement regionalisation as a measure to control economically
      important livestock diseases. Given that regionalisation highlights the
      difference in disease risk between animal subpopulations, this may discourage
      herd managers in low-risk areas from purchasing animals from high-risk areas to
      protect the disease-free status of their herds. Using bovine tuberculosis (bTB)
      in New Zealand as a case example, we develop a novel network simulation model to
      predict how much the frequency of cattle movements between different disease
      control areas (DCAs) could theoretically change if herd managers adopted the
      safest practices (preferentially purchasing cattle from areas with the lowest
      risk of bTB), if herd managers adopted the riskiest practices (preferentially
      purchasing cattle from areas with the greatest risk of bTB), or if herd managers
      made trade decisions completely at random (purchasing cattle without
      consideration for bTB disease risk). A modified configuration wiring algorithm
      was used in the network simulation model to preserve key temporal, spatial, and
      demographic attributes of cattle movement patterns. The simulated frequencies of
      cattle movements between DCAs in each of the three behavioural scenarios were
      compared with the actual frequency of cattle movements that occurred between 1st
      July 2010 and 30th June 2011. Our results showed that the observed frequency of
      cattle movements from high-risk areas into low-risk areas was significantly less
      than if trade decisions were made completely at random, but still significantly
      greater than if herd managers made the safest possible trade decisions. This
      suggests that while New Zealand cattle farmers may have adopted risk-averse
      trading behaviour in response to regionalisation, there are other underlying
      factors driving livestock trade, such as established supplier-buyer relationships
      and heterogeneous individual perceptions towards disease risk, which may reduce
      the potential efficacy of regionalisation as a disease control strategy. Physical
      constraints and socio-psychological factors that determine herd managers'
      livestock trading behaviour warrant further studies to better understand how herd
      managers respond to future livestock disease regulations. The flexibility of a
      network re-wiring framework presented in this study allows such a behavioural
      response to be incorporated into a disease simulation model, which will in turn
      facilitate a better evaluation of disease control strategies.

PMID- 27720026
TI  - Application of slightly acidic electrolyzed water for decontamination of
      stainless steel surfaces in animal transport vehicles.
AB  - The effectiveness of slightly acidic electrolyzed water (SAEW) in reducing
      Escherichia coli, Salmonella typhimurim, Staphylococcus aureus or bacterial
      mixtures on stainless steel surfaces was evaluated and compared its efficacy with
      composite phenol solution for reducing total aerobic bacteria in animal transport
      vehicles. Stainless steel surfaces were inoculated with these strains
      individually or in a mixture, and sprayed with SAEW, composite phenol, or
      alkaline electrolyzed water for 0.5, 1, 1.5 and 2min. The bactericidal activity
      of SAEW increased with increasing available chlorine concentration and spraying
      duration. The SAEW solution of 50mgl-1 of available chlorine concentration showed
      significantly higher effectiveness than composite phenol in reducing the
      pathogens on stainless steel surfaces (P<0.05). Complete inactivation of
      pathogens on stainless steel surfaces were observed after treatment with alkaline
      electrolyzed water followed by SAEW at 50mgl-1 of available chlorine
      concentration for 2min or alkaline electrolyzed water treatment followed by SAEW
      treatment at 90mgl-1 of available chlorine concentration for 0.5min. The efficacy
      of SAEW in reducing total aerobic bacteria in animal transport vehicles was also
      determined. Vehicles in the disinfection booth were sprayed with the same SAEW,
      alkaline electrolyzed water and composite phenol solutions using the automatic
      disinfection system. Samples from vehicle surfaces were collected with sterile
      cotton swabs before and after each treatment. No significant differences in
      bactericidal efficiency were observed between SAEW and composite phenol for
      reducing total aerobic bacteria in the vehicles (P>0.05). SAEW was also found to
      be more effective when used in conjunction with alkaline electrolyzed water.
      Results suggest that the bactericidal efficiency of SAEW was higher than or
      equivalent to that of composite phenol and SAEW may be used as effective
      alternative for reducing microbial contamination of animal transport vehicles.

PMID- 27720027
TI  - Lameness in dairy heifers; impacts of hoof lesions present around first calving
      on future lameness, milk yield and culling risk.
AB  - The importance of lameness in primiparous dairy heifers is increasingly
      recognised. Although it is accepted that clinical lameness in any lactation
      increases the risk of future lameness, the impact of foot lesions during the
      first lactation on long-term lameness risk is less clear. This retrospective
      cohort study aimed to investigate the impacts of foot lesions occurring around
      the time of first calving in heifers on future lameness risk, daily milk yield
      and survival within a dairy herd. Records were obtained for 158 heifers from one
      UK dairy herd. Heifers were examined in 2 month blocks from 2 months pre-calving
      through to 4 months post-calving. Sole lesions and white line lesions were scored
      on a zero to 10 scale and digital dermatitis on a zero to 3 scale. Outcomes
      investigated were; lameness risk based on weekly locomotion scores, average daily
      milk yield and culling risk. Mixed effect models were used to investigate
      associations between maximum lesion scores and outcomes. Lesion scores in the
      highest score categories for claw horn lesions (sole lesions and white line
      lesions) in the 2 to 4 month post-calving period were associated with an
      increased risk of future lameness; heifers with white line lesion scores >=3
      compared with scores zero to 1 and heifers with sole lesion scores >=4 compared
      with score 2, at this time point, had a predicted increased risk of future
      lameness of 1.6 and 2.6 respectively. Sole lesions >=4 were also associated with
      a reduction in average daily milk yield of 2.68kg. Managing heifers to reduce
      claw horn lesions during this time period post-calving may provide health,
      welfare and production benefits for the long-term future of those animals. A
      novel finding from the study was that mild lesion scores compared with scores
      zero to 1, were associated with a reduced risk of future lameness for white line
      lesions and sole lesions occurring in the pre-calving or 2 to 4 months post
      calving periods respectively. Mild sole lesions in the pre-calving period were
      also associated with a reduced risk of premature culling. One hypothesis for this
      result is that a mild insult may result in adaptive changes to the foot leading
      to greater biomechanical resilience and so increased longevity.

PMID- 27720028
TI  - A Bayesian micro-simulation to evaluate the cost-effectiveness of interventions
      for mastitis control during the dry period in UK dairy herds.
AB  - Importance of the dry period with respect to mastitis control is now well
      established although the precise interventions that reduce the risk of acquiring
      intramammary infections during this time are not clearly understood. There are
      very few intervention studies that have measured the clinical efficacy of
      specific mastitis interventions within a cost-effectiveness framework so there
      remains a large degree of uncertainty about the impact of a specific intervention
      and its costeffectiveness. The aim of this study was to use a Bayesian framework
      to investigate the cost-effectiveness of mastitis controls during the dry period.
      Data were assimilated from 77 UK dairy farms that participated in a British
      national mastitis control programme during 2009-2012 in which the majority of
      intramammary infections were acquired during the dry period. The data consisted
      of clinical mastitis (CM) and somatic cell count (SCC) records, herd management
      practices and details of interventions that were implemented by the farmer as
      part of the control plan. The outcomes used to measure the effectiveness of the
      interventions were i) changes in the incidence rate of clinical mastitis during
      the first 30days after calving and ii) the rate at which cows gained new
      infections during the dry period (measured by SCC changes across the dry period
      from <200,000cells/ml to >200,000cells/ml). A Bayesian one-step microsimulation
      model was constructed such that posterior predictions from the model incorporated
      uncertainty in all parameters. The incremental net benefit was calculated across
      10,000 Markov chain Monte Carlo iterations, to estimate the cost-benefit (and
      associated uncertainty) of each mastitis intervention. Interventions identified
      as being cost-effective in most circumstances included selecting dry-cow therapy
      at the cow level, dry-cow rations formulated by a qualified nutritionist, use of
      individual calving pens, first milking cows within 24h of calving and spreading
      bedding evenly in dry-cow yards. The results of this study highlighted the
      efficacy of specific mastitis interventions in UK conditions which, when
      incorporated into a costeffectiveness framework, can be used to optimize decision
      making in mastitis control. This intervention study provides an example of how an
      intuitive and clinically useful Bayesian approach can be used to form the basis
      of an on-farm decision support tool.

PMID- 27720029
TI  - Bovine respiratory syncytial virus and bovine coronavirus antibodies in bulk tank
      milk - risk factors and spatial analysis.
AB  - Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCoV) are
      considered widespread among cattle in Norway and worldwide. This cross-sectional
      study was conducted based on antibody-ELISA of bulk tank milk (BTM) from 1347
      herds in two neighboring counties in western Norway. The study aims were to
      determine the seroprevalence at herd level, to evaluate risk factors for BRSV and
      BCoV seropositivity, and to assess how these factors were associated with the
      spatial distribution of positive herds. The overall prevalence of BRSV and BCoV
      positive herds in the region was 46.2% and 72.2%, respectively. Isopleth maps of
      the prevalence risk distribution showed large differences in prevalence risk
      across the study area, with the highest prevalence in the northern region. Common
      risk factors of importance for both viruses were herd size, geographic location,
      and proximity to neighbors. Seropositivity for one virus was associated with
      increased odds of seropositivity for the other virus. Purchase of livestock was
      an additional risk factor for BCoV seropositivity, included in the model as in
      degree, which was defined as the number of incoming movements from individual
      herds, through animal purchase, over a period of five years. Local dependence and
      the contribution of risk factors to this effect were assessed using the residuals
      from two logistic regression models for each virus. One model contained only the
      x- and y- coordinates as predictors, the other had all significant predictors
      included. Spatial clusters of high values of residuals were detected using the
      normal model of the spatial scan statistic and visualized on maps. Adjusting for
      the risk factors in the final models had different impact on the spatial clusters
      for the two viruses: For BRSV the number of clusters was reduced from six to
      four, for BCoV the number of clusters remained the same, however the log
      likelihood ratios changed notably. This indicates that geographical differences
      in proximity to neighbors, herd size and animal movements explain some of the
      spatial clusters of BRSV- and BCoV seropositivity, but far from all. The
      remaining local dependence in the residuals show that the antibody status of one
      herd is influenced by the antibody status of its neighbors, indicating the
      importance of indirect transmission and that increased biosecurity routines might
      be an important preventive strategy.

PMID- 27720030
TI  - Assessing, and understanding, European organic dairy farmers' intentions to
      improve herd health.
AB  - Many believe the health status of organic dairy herds in Europe should be
      improved to meet consumers' and legislators' expectations to improve animal
      welfare. This paper reports on a study in four countries that examined dairy
      farmers' intentions towards improving the health status of their organic herds
      through the use of the Theory of Planned Behaviour. It was found that farmers
      across the countries were positive about taking additional preventative measures
      to improve the health status of their herds. They believed this would not only
      improve herd physical performance, such as milk yield and fertility, but also
      achieve greater cost effectiveness and improved job satisfaction for them. Most
      study farmers would implement a tailored package of improvement measures designed
      by the study team with higher uptake most likely being by younger farmers, those
      who make greater use of veterinarians and professional advisory services, and
      those supplying specialist milk-marketing chains. Furthermore, farmers will be
      most likely to take-up additional health promotion if compatible with their
      everyday activities and if they have strong business performance goals aimed at
      maximising the physical performance of the herd.

PMID- 27720032
TI  - Sixteen years on.

PMID- 27720031
TI  - A retrospective study and predictive modelling of Newcastle Disease trends among
      rural poultry of eastern Zambia.
AB  - Newcastle Disease (ND) is a highly infectious disease of poultry that seriously
      impacts on food security and livelihoods of livestock farmers and communities in
      tropical regions of the world. ND is a constant problem in the eastern province
      of Zambia which has more than 740 000 rural poultry. Very few studies give a
      situational analysis of the disease that can be used for disease control planning
      in the region. With this background in mind, a retrospective epidemiological
      study was conducted using Newcastle Disease data submitted to the eastern
      province headquarters for the period from 1989 to 2014. The study found that
      Newcastle Disease cases in eastern Zambia followed a seasonal and cyclic pattern
      with peaks in the hot dry season (Overall Seasonal Index 1.1) as well as cycles
      every three years with an estimated provincial incidence range of 0.16 to 1.7%
      per year. Annual trends were compared with major intervention policies
      implemented by the Zambian government, which often received donor support from
      the international community during the study period. Aid delivered through
      government programmes appeared to have no major impact on ND trends between 1989
      and 2014 and reasons for this are discussed. There were apparent spatial shifts
      in districts with outbreaks over time which could be as a result of veterinary
      interventions chasing outbreaks rather than implementing uniform control. Data
      was also fitted to a predictive time series model for ND which could be used to
      plan for future ND control. Time series modelling showed an increasing trend in
      ND annual incidence over 25 years if existing interventions continue. A different
      approach to controlling the disease is needed if this trend is to be halted.
      Conversely, the positive trend may be a function of improved reporting by farmers
      as a result of more awareness of the disease.

PMID- 27720033
TI  - Patient, Family Centred Care.

PMID- 27720034
TI  - Parent and nurse perceptions on the quality of family-centred care in 11 European
      NICUs.
AB  - BACKGROUND: Family-centred care (FCC) is a state-of-the-art practice in neonatal
      intensive care units (NICU) based on its shown benefits on the well-being of both
      infants and parents. However, there is no systematic knowledge about how FCC is
      implemented in different European contexts. OBJECTIVES: To describe parents'
      presence and the quality of FCC from the perspectives of mothers, fathers and
      nurses in 11 European NICUs. METHODS: A prospective survey was conducted in
      Finland, Sweden, Norway, Estonia, Spain and Italy. The perceived quality of FCC
      was measured using 8 text-message questions sent to the parents' mobile phones,
      one question each day, during the infant's hospital stay. Nurses answered
      corresponding questions through a Web questionnaire during a 3-month period. The
      responses were rated on a 7-point Likert scale. Parents who were not present in
      the unit during the day used a "0" response. RESULTS: A total of 262 families of
      preterm infants born before 35 gestational weeks participated in the study.
      Mothers gave 5045 responses, fathers gave 3971 responses and nurses gave 11,132
      answers. The mothers were present during 92.7% and the fathers during 77.9% of
      the study days. The mothers rated the quality of FCC slightly higher than the
      fathers did (5.8 [95% CI 5.7-5.9] vs. 5.7 [95% CI 5.6-5.8], mean difference of
      0.12 [95% CI 0.05-0.2], p<0.001). There was wide variation in the parents'
      presence and the quality of FCC between the units. The weakest aspects of FCC
      were emotional support, parents' participation in decision-making and fathers'
      participation in infant care. The perceived quality of FCC between the nurses and
      parents were comparable. CONCLUSIONS: This study showed a high perceived quality
      of FCC in 11 European units, as indicated by both parents and nurses. The
      innovative data-collection method and instrument successfully quantified each
      unit's FCC profile for further quality improvement and should be trialled in
      other NICUs and countries.

PMID- 27720035
TI  - Kinetics of docosahexaenoic acid ethyl ester accumulation in dog plasma and
      brain.
AB  - This study explores dog plasma and brain fatty acid composition achieved after
      long-term supplementation at high DHA doses. A 90% concentrate of DHA Ethyl Ester
      (DHA-EE) administered by oral gavage to Beagle dogs at doses of 100, 500, 1000,
      and 2000mg/kg bw/day for 8 weeks resulted in DHA increases in both plasma and
      brain. In a subsequent 9-month study, DHA-EE was administered at 150, 1000 and
      2000mg/kg bw/day. Plasma DHA increased between 150 and 1000mg/kg bw/day but not
      between 1000 and 2000mg/kg bw/day and there were increases from Day 1to 92 but
      not between days 92 and 273. Doses >500mg/kg bw/day in the 8-week and all doses
      in the 9-month study resulted in DHA increases in the brain. The dose of 150mg/k
      gbw/day is sufficient to achieve maximal brain concentrations if DHA is
      administered chronically. For shorter than 6 months of supplementation, higher
      doses are required.

PMID- 27720038
TI  - The effect of n-3 LCPUFA supplementation on oxidative stress and inflammation in
      the placenta and maternal plasma during pregnancy.
AB  - Pregnancy represents a state of heightened oxidative stress and inflammation, and
      these processes are further increased in pregnancy complications. The quality of
      the maternal diet is directly associated with maternal health and wellbeing,
      pregnancy and fetal outcomes, as well as the risk of pregnancy complications.
      Long chain polyunsaturated fatty acids (LCPUFAs) have significant potential to
      modify placental and fetal lipid environments and thereby modulate health
      outcomes. The omega-3 (n-3) LCPUFA in particular have been shown to exhibit both
      antioxidant and anti-inflammatory properties, and have potential therapeutic
      applications in reducing oxidative damage and inflammation during pregnancy. The
      purpose of this review is to provide an overview of our current understanding of
      the impact of maternal n-3 LCPUFA supplementation on oxidative stress and
      inflammation during pregnancy, with a particular focus on effects on the mother
      and the placenta.

PMID- 27720036
TI  - Differences in long chain polyunsaturates composition and metabolism in male and
      female rats.
AB  - Human studies and some animal work have shown more docosahexaenoic acid (DHA) and
      arachidonic acid (ARA) was accumulated or converted from precursors in females
      compared to males. This study explored in-depth the effect of gender on fatty
      acid composition and polyunsaturated fatty acid metabolism in rats fed one of two
      well-defined diets containing 10% total fat. One diet contained 15% of linoleic
      acid (LA) and 3% of alpha-linolenic acid (ALA) of the total fatty acids (LA+ALA
      diet), while the other diet contained 15% LA and 0.05% ALA (LA diet). At the age
      of 20 weeks, all animals were orally administered a single dose of a mixture of
      deuterium-labeled LA and ALA. Caudal venous blood was then drawn at 0, 2, 4, 8,
      12, 24, 48, 96 and 168h. The concentrations of the deuterated precursors and
      their metabolites in plasma total lipids were quantified by GC/MS negative
      chemical ionization. Endogenous fatty acids were quantified by GC/FID analysis.
      When expressed as the percentage of oral dosage, female rats accumulated more
      precursors and more products, deuterated DHA and deuterated n-6 docosapentaenoic
      acid (2H5-DPAn-6), in plasma than did male rats in both the LA+ALA diet and the
      LA diet. For the endogenous non-labeled PUFA, greater concentrations of DHA and
      DPAn-6 were similarly observed in female rats compared to males within each diet.
      A lower concentration of non-labeled ARA was observed only in female rats fed the
      LA+ALA diet. In summary, greater endogenous and exogenous DHA and DPAn-6 was
      observed in female rat plasma and this was independent of dietary ALA status.

PMID- 27720037
TI  - Inflammatory F2-isoprostane, prostaglandin F2alpha, pentraxin 3 levels and breast
      cancer risk: The Swedish Mammography Cohort.
AB  - INTRODUCTION: Breast cancer is a common cancer among women. Identifying cellular
      participation of F2-isoprostane, prostaglandin F2alpha (PGF2alpha) and pentraxin
      3 (PTX3) in cancer we evaluated whether their prediagnostic systemic levels that
      originate from different inflammatory pathways were associated with breast cancer
      risk. METHODS: Seventy-eight breast cancer cases diagnosed after blood collection
      and 797 controls from the Swedish Mammography Cohort were analysed for urinary F2
      isoprostane, PGF2alpha and plasma PTX3 levels. RESULTS: None of the biomarkers
      investigated were significantly associated with breast cancer risk. However,
      there was the suggestion of an inverse association with PTX3 with multivariable
      adjusted ORs (95% CI) of 0.56 (95% CI=0.29-1.06) and 0.67 (95% CI=0.35-1.28) for
      the second and third tertiles, respectively (ptrend=0.20). No associations were
      observed between F2-isoprostane (OR=0.87; 95% CI=0.48-1.57; ptrend=0.67) and
      PGF2alpha metabolite (OR=1.03; 95% CI=0.56-1.88; ptrend=0.91) comparing the top
      to bottom tertiles. CONCLUSIONS: The systemic levels of F2-isoprostane, PGF2alpha
      and PTX3 witnessed in women who later developed breast cancer may not provide
      prognostic information regarding tumor development in spite of their known
      involvement in situ cellular context. These observations may indicate that other
      mechanisms exist in controlling cellular formation of F2-isoprostane, PGF2alpha
      and PTX3 and their systemic availability in breast cancer patients.

PMID- 27720039
TI  - Risk factors associated with plasma omega-3 fatty acid levels in patients with
      suspected coronary artery disease.
AB  - INTRODUCTION: We sought to determine the associations between plasma
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels and various
      cardiovascular risk factors and with the use of fish oil supplements (FOS).
      PATIENTS AND METHODS: Patients with suspected coronary artery disease (CAD)
      undergoing cardiac catheterization (n=433) were studied. Serum fatty acid (FA)
      composition, the concentrations of lipids and biomarkers of oxidative stress, and
      dietary/lifestyle factors were measured. RESULTS: FOS use was associated with a
      higher plasma EPA+DHA levels (3.7+/-1.5 vs. 2.6+/-1.1%, p<0.0001). However, there
      was no relationship between FOS dose (mg/day) and EPA+DHA levels in 76 patients
      reporting FOS use (r=-0.21, p=0.07). Lower levels were inversely associated with
      risk factor profiles including lower ApoB100/ApoA1 ratios (p<0.001). DISCUSSION
      AND CONCLUSIONS: Higher EPA+DHA levels characterized patients with lower CAD
      risk. The lack of relations between FOS dose and plasma EPA+DHA levels likely
      reflects uncaptured variability in EPA+DHA content of supplements.

PMID- 27720040
TI  - Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline
      in pediatric cystic fibrosis patients: a pilot study.
AB  - BACKGROUND: Airway inflammation is a significant contributor to the morbidity of
      cystic fibrosis (CF) disease. One feature of this inflammation is the production
      of oxygenated metabolites, such as prostaglandins. Individuals with CF are known
      to have abnormal metabolism of fatty acids, typically resulting in reduced levels
      of linoleic acid (LA) and docosahexaenoic acid (DHA). METHODS: This is a
      randomized, double-blind, cross-over clinical trial of DHA supplementation with
      endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M)
      levels. Patients with CF age 6-18 years with pancreatic insufficiency were
      recruited. Each participant completed 3 four-week study periods: DHA at two
      different doses (high dose and low dose) and placebo with a minimum 4 week wash
      out between each period. Blood, urine, and exhaled breath condensate (EBC) were
      collected at baseline and after each study period for measurement of plasma fatty
      acids as well as prostaglandin E metabolites. RESULTS: Seventeen participants
      were enrolled, and 12 participants completed all 3 study periods. Overall, DHA
      supplementation was well tolerated without significant adverse events. There was
      a significant increase in plasma DHA levels with supplementation, but no
      significant change in arachidonic acid (AA) or LA levels. However, at baseline,
      AA levels were lower and LA levels were higher than previously reported for
      individuals with CF. Urine PGE-M levels were elevated in the majority of
      participants at baseline, and while levels decreased with DHA supplementation,
      they also decreased with placebo. CONCLUSIONS: Urine PGE-M levels are elevated at
      baseline in this cohort of pediatric CF patients, but there was no significant
      change in these levels with DHA supplementation compared to placebo. In addition,
      baseline plasma fatty acid levels for this cohort showed some difference to prior
      reports, including higher levels of LA and lower levels of AA, which may reflect
      changes in clinical care, and consequently warrants further investigation.

PMID- 27720041
TI  - Enriched dairy fat matrix diet prevents early life lipopolysaccharide-induced
      spatial memory impairment at adulthood.
AB  - Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical
      for brain development and later life cognitive functions. The main brain PUFAs
      are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for
      the n-6 family, which are provided to the post-natal brain by breast milk or
      infant formula. Recently, the use of dairy lipids (DL) in replacement of
      vegetable lipids (VL) was revealed to potently promote the accretion of DHA in
      the developing brain. Brain DHA, in addition to be a key component of brain
      development, display potent anti-inflammatory activities, which protect the brain
      from adverse inflammatory events. In this work, we evaluated the protective
      effect of partial replacement of VL by DL, supplemented or not with DHA and ARA,
      on post-natal inflammation and its consequence on memory. Mice were fed with
      diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal
      VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp
      DL) from the first day of gestation until adulthood. At post-natal day 14
      (PND14), pups received a single administration of the endotoxin
      lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and
      neurogenesis were measured. In a second set of experiments, memory and
      neurogenesis were measured at adulthood. Overall, our data showed that lipid
      quality of the diet modulates early life LPS effect on microglia phenotype, brain
      cytokine expression and neurogenesis at PND14 and memory at adulthood. In
      particular, Bal DL diet protects from the adverse effect of early life LPS
      exposure on PND14 neurogenesis and adult spatial memory.

PMID- 27720042
TI  - Endocrine uncoupling of the trade-off between reproduction and somatic
      maintenance in eusocial insects.
AB  - In most animals reproduction trades off with somatic maintenance and survival.
      Physiologically this trade-off is mediated by hormones with opposite effects on
      reproduction and maintenance. In many insects, this regulation is achieved by an
      endocrine network that integrates insulin-like/IGF-1 signaling (IIS), juvenile
      hormone (JH), and the yolk precursor vitellogenin (Vg) (or, more generally, yolk
      proteins [YPs]). Downregulation of this network promotes maintenance and survival
      at the expense of reproduction. Remarkably, however, queens of highly eusocial
      social insects exhibit both enormous reproductive output and longevity, thus
      escaping the trade-off. Here we argue - based on recent evidence - that the
      proximate reason for why eusocial insects can decouple this trade-off is that
      they have evolved a different 'wiring' of the IIS-JH-Vg/YP circuit.

PMID- 27720043
TI  - Why do social insect queens live so long? Approaches to unravel the sociality
      aging puzzle.
AB  - Social insects are characterized by an apparent reshaping of the
      fecundity/longevity trade-off with sociality. Currently, we have only sketchy
      information about the potential underlying causes and mechanisms of aging and
      senescence which in addition are restricted to few model insect organisms (mainly
      the fruit fly Drosophila melanogaster and the honey bee Apis mellifera). How can
      we gain a more thorough understanding how sociality shapes senescence and the
      fecundity/longevity trade-off? By reviewing available literature, I propose a
      comparative approach that offers the opportunity to gain fundamental insights
      into uncovering the basis for this life history trade-off and its reshaping with
      sociality.

PMID- 27720044
TI  - Temperature-dependent effects on the replication and transmission of arthropod
      borne viruses in their insect hosts.
AB  - The transmissibility of vector borne viruses can be affected by a combination of
      factors, both extrinsic (climatic changes, temperature, urbanization, among
      others) and intrinsic (genetics, life span, immunity, among others). Temperature
      is of particular importance since the insect vectors of arthropod-borne viruses
      (arboviruses) are ectothermic and acutely susceptible to temperature changes.
      Modeling suggests that with increasing global temperature and urbanization,
      arboviral diseases will continue to emerge or reemerge. This review highlights
      current literature regarding temperature-dependent effects on virus-vector
      interactions and their potential to influence the transmission dynamics and
      epidemiology of arboviral diseases.

PMID- 27720046
TI  - The male has done his work - the male may go.
AB  - Perennial social insects are famous for the extraordinary longevity of their
      queens. While the lifespan of termite kings matches those of queens, males of
      social Hymenoptera are usually considered to die after one or a few copulations.
      While this is true in species with highly synchronized nuptial flights, in others
      males mate over much longer periods. Male longevity is not correlated with the
      life span of queens but appears to be adapted to mating opportunities. This is
      demonstrated by the extreme life span of Cardiocondyla ant males, which
      monopolize mating with virgin queens over many months. Cardiocondyla offers the
      opportunity to investigate why male longevity varies even among closely related
      taxa and how male age affects sperm and offspring quality.

PMID- 27720047
TI  - Patterns of longevity across a sociality gradient in vespid wasps.
AB  - The reversal of the fecundity/longevity tradeoff in social insects is striking,
      but we lack understanding of when and how this reversal evolved. Vespid wasps are
      excellent models for studying social evolution because species show different
      levels of sociality from solitary to primitively to advanced eusocial. We provide
      the first synthesis of existing, but scanty, data available on longevity in
      vespids. We explore whether the fecundity/longevity tradeoff reversal is
      exaggerated in species with more derived sociality. Although the reversal is
      evident in primitively social wasps, the available data suggest it may be
      stronger in large-colonied species, which show a trend toward shorter worker
      longevity. More data are needed on additional species and underlying mechanisms,
      but vespids hold promise for understanding the evolution of the
      fecundity/longevity tradeoff reversal.

PMID- 27720045
TI  - Abiotic and biotic factors affecting the replication and pathogenicity of bee
      viruses.
AB  - Bees are important pollinators of plants in both agricultural and non
      agricultural landscapes. Recent losses of both managed and wild bee species have
      negative impacts on crop production and ecosystem diversity. Therefore, in order
      to mitigate bee losses, it is important to identify the factors most responsible.
      Multiple factors including pathogens, agrochemical exposure, lack of quality
      forage, and reduced habitat affect bee health. Pathogen prevalence is one factor
      that has been associated with colony losses. Numerous pathogens infect bees
      including fungi, protists, bacteria, and viruses, the majority of which are RNA
      viruses including several that infect multiple bee species. RNA viruses readily
      infect bees, yet there is limited understanding of their impacts on bee health,
      particularly in the context of other stressors. Herein we review the influence
      environmental factors have on the replication and pathogenicity of bee viruses
      and identify research areas that require further investigation.

PMID- 27720048
TI  - Manipulation of hosts and vectors by plant viruses and impact of the environment.
AB  - The effect of environmental factors on the efficiency of plant virus transmission
      is extremely difficult to predict, because they obviously impact concomitantly
      multiple steps of the complex three-way plant-virus-vector interaction. This
      review summarizes the diversity of the relationship between plants, viruses and
      insect vectors, and highlights the numerous phases of this process that can be
      altered by the virus in ways that can potentially enhance its transmission
      success. Many of the reported cases are often considered to be possible viral
      manipulations acting through modifications of the physiology of the host plant,
      indirectly reaching to the insect vector. Plants are extremely responsive to
      environmental fluctuations and so interferences with these putative viral
      manipulations are highly expected. The role of environmental factors in plant
      virus transmission can thus be envisaged solely in the context of this
      complexity. It is only briefly evoked here because this field of research is in
      its infancy and currently suffers from an impressive lack of experimental data.

PMID- 27720049
TI  - Viral receptors of the gut: vector-borne viruses of medical importance.
AB  - Arthropods transmit several medically important arboviruses that cause diseases
      in humans. Therapeutic strategies to treat or prevent diseases transmitted by the
      arthropods are limiting. Understanding the role of arthropod gut receptors in the
      interactions with various arboviruses would provide important means for the
      development of a strong anti-vector vaccine. In this review, we summarize some of
      the potential findings in the field of arthropod gut receptors for tick-borne or
      mosquito-borne viruses and discuss their relevance in the development of a broad
      spectrum transmission-blocking vaccine to treat or control various diseases
      caused by arboviruses.

PMID- 27720050
TI  - Life history evolution in social insects: a female perspective.
AB  - Social insects are known for their unusual life histories with fecund, long-lived
      queens and sterile, short-lived workers. We review ultimate factors underlying
      variation in life history strategies in female social insects, whose social life
      reshapes common trade-offs, such as the one between fecundity and longevity.
      Interspecific life history variation is associated with colony size, mediated by
      changes in division of labour and extrinsic mortality. In addition to the ratio
      of juvenile to adult mortality, social factors such as queen number influence
      life history trajectories. We discuss two hypotheses explaining why queen
      fecundity and lifespan is higher in single-queen societies and suggest further
      research directions on the evolution of life history variation in social insects.

PMID- 27720051
TI  - Fitness and aging in Cardiocondyla obscurior ant queens.
AB  - Easy maintenance, controlled mating and short generation time make Cardiocondyla
      obscurior an interesting model for social insect aging research. Using this ant
      we have begun to study the proximate genomic relationship between mating and
      aging. Although mating in general has a positive effect and results in fertile
      queens with long life but drastically reduced metabolic rates, mating can also
      dramatically reduce queen fitness. Here we review a decade of research on factors
      affecting queen aging rate and contrast these findings with studies on honeybees
      and solitary aging models. We conclude by giving a brief outlook of what is to be
      expected from this model in coming years.

PMID- 27720053
TI  - A critical look at proximate causes of social insect senescence: damage
      accumulation or hyperfunction?
AB  - Social insects have received attention for their extreme lifespan variation and
      reversal of the fecundity/longevity trade-off. However, proximate causes of
      senescence in general are disputed, and social insects often fail to meet the
      predictions of prevailing models. We present evidence for and against the long
      held free radical theory of aging in social insects, and consider the application
      of the competing hyperfunction theory. Current results present problems for both
      theories, and a more complex picture of the biological processes involved
      emerges. The eusocial life style might allow colonies to allocate damage in ways
      that create seemingly senescence-free life histories. Only experimental
      approaches characterizing multiple senescence factors simultaneously will shed
      light on how social insects defy the conventions of senescence.

PMID- 27720052
TI  - Ties between ageing plasticity and reproductive physiology in honey bees (Apis
      mellifera) reveal a positive relation between fecundity and longevity as
      consequence of advanced social evolution.
AB  - Honey bees (Apis mellifera) are the best studied model of ageing among the social
      insects. As in other social insects, the reproductive queen far outlives her non
      reproductive workers despite developing from the same genome in the same colony
      environment. Thus, the different social roles of the two female castes are
      critical for the profound phenotypic plasticity. In several special cases, such
      as the reproductive workers of Apis mellifera capensis, within-caste plasticity
      enables further studies of the fecundity-longevity syndrome in honey bees. At
      present, molecular evidence suggests that a reorganization of physiological
      control pathways may facilitate longevity of reproductive individuals. However,
      the social role and social environment of the different colony members are also
      very important and one of the key future questions is how much social
      facilitation versus internal regulation is responsible for the positive
      association between fecundity and longevity in honey bees.

PMID- 27720054
TI  - Lifespan divergence between social insect castes: challenges and opportunities
      for evolutionary theories of aging.
AB  - The extraordinarily long lifespans of queens (and kings) in eusocial insects and
      the strikingly large differences in life expectancy between workers and queens
      challenge our understanding of the evolution of aging and provide unique
      opportunities for studying the causes underlying adaptive variation in lifespan
      within species. Here we review the major evolutionary theories of aging, focusing
      on their scope and limitations when applied to social insects. We show that
      reproductive division of labor, interactions between kin, caste-specific gene
      regulation networks, and the integration of colony-level trade-offs with
      individual-level trade-offs provide challenges to the classical theories We
      briefly indicate how these challenges could be met in future models of adaptive
      phenotypic plasticity in lifespan between and within different castes.

PMID- 27720055
TI  - Evolutionary origin of pathogenic arthropod-borne viruses-a case study in the
      family Bunyaviridae.
AB  - Arthropod-borne viruses have a dual-host tropism and their transmission requires
      the infection of two disparate hosts, arthropods and vertebrates. Arboviruses
      occur in several RNA families that also contain viruses with a monotropism for
      either arthropods or vertebrates. The evolutionary origin of the dual-host
      tropism of arboviruses was recently identified for the family Bunyaviridae.
      Bunyaviruses were suggested to have evolved from viruses that are restricted to
      arthropods as hosts (arthropod-specific viruses). Additional findings of an
      immense genetic diversity of bunyaviruses in non-blood feeding arthropods support
      the hypothesis of an arthropod origin of vertebrate-pathogenic bunyaviruses.

PMID- 27720056
TI  - Chapter 6. Comparative genomic approaches to investigate molecular traits
      specific to social insects.
AB  - Ageing is a feature of nearly all known organisms and, by its connection to
      survival, appears to trade off with fecundity. However, in some organisms such as
      in queens of social insects, this negative relation appears reversed and
      individuals live long and reproduce much. Since new experimental techniques,
      transcriptomes and genomes of many social insects have recently become available,
      a comparison of these data in a phylogenetic framework becomes feasible. This
      allows the study of general trends, species specific oddities and evolutionary
      dynamics of the molecular properties and changes which underlie ageing, fecundity
      and the reversal of this negative association. In the framework of social insect
      evolution, we review the most important recent insights, computational methods,
      their applications and data resources which are available.

PMID- 27720057
TI  - Viral receptors of the gut: insect-borne propagative plant viruses of
      agricultural importance.
AB  - Insect-borne propagative plant viruses of agricultural importance are transmitted
      by sap-sucking insects. Although the infection routes of these viruses within the
      bodies of insect vectors are well established, cellular receptors on the
      microvilli, intercellular junctions, and basal lamina for mediating viral entry
      or spread in insect gut epithelium have not been well identified or
      characterized. Recent trends in the field are opening questions on how viruses
      exploit actin-based tubule motility to overcome insect gut epithelium barriers
      after viral entry in epithelium. Advances in insect cell lines, genome
      sequencing, reverse genetic systems and others not yet developed technologies are
      needed to find and characterize the counterpart receptors in vectors and to
      design strategies to interfere with viral transmission.

PMID- 27720058
TI  - Facultative social insects can provide insights into the reversal of the
      longevity/fecundity trade-off across the eusocial insects.
AB  - In eusocial insects, reversal of the fecundity/longevity trade-off and extreme
      differences in life histories between castes of the same species garner
      scientific and public interest. Facultative social species at the threshold of
      sociality, in which individuals are socially plastic, provide an excellent
      opportunity to understand the causes and mechanisms underlying this reversal in
      life history trade-off associated with eusociality. We briefly present the
      ultimate factors favoring sociality and the association between fecundity and
      longevity in facultative eusocial insects, including kin selection and disposable
      soma, as well as proximate mechanisms observed in such species, such as
      differences in hormone titers and functions. Potential genetic underpinnings of
      lifespan and fecundity differences between castes are discussed and future
      research directions are proposed.

PMID- 27720059
TI  - Editorial overview: Vectors and medical and veterinary entomology: Summary.

PMID- 27720060
TI  - Editorial overview: Social insects: aging and the re-shaping of the
      fecundity/longevity trade-off with sociality.

PMID- 27720061
TI  - Nurses' Call to Action: Supporting a Strong Global HIV Nursing Workforce.

PMID- 27720062
TI  - Activism at AIDS2016.

PMID- 27720063
TI  - Impressions of the 21st International AIDS Conference in Durban, South Africa.

PMID- 27720064
TI  - Beliefs about HIV in Low-Income Nicaraguan Women.
AB  - In Latin America, women account for more than 30% of all HIV cases. However,
      minimal research has been reported on women's beliefs about HIV in Latin America.
      The purpose of our qualitative study was to describe HIV beliefs in a sample of
      low-income Nicaraguan women living in a squatter settlement in Managua.
      Participants (N = 34) were women who participated in four focus groups. The mean
      age of the women was 40 years, and the mean education level was 5 years. Women
      reported a plurality of beliefs about HIV, some of which were biomedically
      accurate while others were not. Themes of stigma and rejection emerged across all
      focus group discussions. Younger women were more informed than older women. The
      findings are instructive for nurses working with Nicaraguan women and may be
      useful in developing HIV education interventions with similar populations in
      other Latin American countries or with immigrants from those countries.

PMID- 27720065
TI  - Morning blood pressure surge and markers of cardiovascular alterations in
      untreated middle-aged hypertensive subjects.
AB  - The purpose of the study was to evaluate the degree of morning blood pressure
      surge (MBPS) and its relationship with markers of cardiovascular alterations in
      untreated middle-aged hypertensives. We studied 241 patients (mean age, 36.6 +/-
      10.7 years). Subjects with higher sleep-through MBPS (st-MBPS) were older (P =
      .003), had higher carotid intima-media thickness (cIMT) (P = .05) and lower E/A
      ratio (P = .01) than those with lower MBPS. Subjects with higher prewakening MBPS
      (pw-MBPS) had significantly higher deceleration time (P = .01) compared with
      those with lower pw-MBPS. St-MBPS correlated significantly with age, cIMT values,
      24-hour systolic and diastolic BP, and systolic BP night-time fall. The
      significant correlations between pw-MBPS and cIMT values, deceleration time, 24
      hour diastolic BP and systolic BP night-time fall were observed. A relationship
      between MBPS and cardiovascular alterations was observed both in dippers and
      nondippers, although in non-dippers, it was less pronounced. The results may
      imply a possible link between MBPS and markers of cardiovascular alterations in
      untreated hypertensive subjects.

PMID- 27720066
TI  - Effect of visit-to-visit blood pressure variability on cardiovascular events in
      patients with coronary artery disease and well-controlled blood pressure.
AB  - This post hoc analysis of CAMELOT and PREVENT analyzed the impact of blood
      pressure variability (BPV, assessed as within-subject standard deviation of SBP
      from 12 weeks onward) on the incidence of major adverse cardiovascular events
      (MACE, defined according to original studies). Patients (n = 1677 CAMELOT; n =
      776 PREVENT) were stratified by BPV quartile. Regardless of study, BPV was
      significantly lower for amlodipine versus other treatments. In CAMELOT, a
      significant association between BPV quartile and MACE was observed with
      amlodipine treatment. Significant associations between BPV quartile and MACE were
      observed for both studies, when analyzed overall (adjusting for treatment). In
      CAMELOT, with amlodipine treatment, an increased risk for MACE was observed with
      high (BPV >= Q3) versus low BPV (< Q1; adjusting for characteristics and risk
      factors). In both studies, increased risk for MACE was observed for BPV >= Q3
      versus BPV < Q1 (analyzed overall, adjusting for treatment and covariates). For
      both studies, BPV, but not mean SBP, was associated with cardiovascular events.
      BPV was associated with cardiovascular outcomes in patients with CAD and well
      controlled BP.

PMID- 27720067
TI  - Cuticle formation and pigmentation in beetles.
AB  - Adult beetles (Coleoptera) are covered primarily by a hard exoskeleton or
      cuticle. For example, the beetle elytron is a cuticle-rich highly modified
      forewing structure that shields the underlying hindwing and dorsal body surface
      from a variety of harmful environmental factors by acting as an armor plate. The
      elytron comes in a variety of colors and shapes depending on the coleopteran
      species. As in many other insect species, the cuticular tanning pathway begins
      with tyrosine and is responsible for production of a variety of melanin-like and
      other types of pigments. Tanning metabolism involves quinones and quinone
      methides, which also act as protein cross-linking agents for cuticle
      sclerotization. Electron microscopic analyses of rigid cuticles of the red flour
      beetle, Tribolium castaneum, have revealed not only numerous horizontal chitin
      protein laminae but also vertically oriented columnar structures called pore
      canal fibers. This structural architecture together with tyrosine metabolism for
      cuticle tanning is likely to contribute to the rigidity and coloration of the
      beetle exoskeleton.

PMID- 27720068
TI  - The mechanism controlling phenotypic plasticity of body color in the desert
      locust: some recent progress.
AB  - Schistocerca gregaria exhibits density-dependent body color polyphenism. Nymphs
      occurring at low population densities show green-brown polyphenism. They show
      phase polyphenism and develop black patterns at high population densities. Recent
      studies suggest a third type of polyphensim, that is, homochromy, a response to
      background color. Laboratory experiments that considered homochromy suggest that
      humidity is not directly involved in green-brown polyphenism and that odor from
      other individuals does not induce black patterns. Black patterns can be induced
      in isolated nymphs by video images of locusts and tadpoles. Juvenile hormone and
      [His7]-corazonin control body color in locusts. The gene encoding the latter has
      been identified for S. gregaria and Locusta migratoria, and its key role in
      controlling black patterning has been demonstrated.

PMID- 27720070
TI  - Genes controlling mimetic colour pattern variation in butterflies.
AB  - Butterfly wing patterns are made up of arrays of coloured scales. There are two
      genera in which within-species variation in wing patterning is common and has
      been investigated at the molecular level, Heliconius and Papilio. Both of these
      species have mimetic relationships with other butterfly species that increase
      their protection from predators. Heliconius have a 'tool-kit' of five genetic
      loci that control colour pattern, three of which have been identified at the gene
      level, and which have been repeatedly used to modify colour pattern by different
      species in the genus. By contrast, the three Papilio species that have been
      investigated each have different genetic mechanisms controlling their polymorphic
      wing patterns.

PMID- 27720069
TI  - Functional analysis of genes involved in color pattern formation in Lepidoptera.
AB  - In addition to the genome editing technology, novel functional analyses using
      electroporation are powerful tools to reveal the gene function in the color
      pattern formation. Using these methods, several genes involved in various larval
      color pattern formation are clarified in the silkworm Bombyx mori and some
      Papilio species. Furthermore, the coloration pattern mechanism underlying the
      longtime mystery of female-limited Batesian mimicry of Papilio polytes has been
      recently revealed. This review presents the recent progress on the molecular
      mechanisms and evolutionary process of coloration patterns contributing to
      various mimicry in Lepidoptera, especially focusing on the gene function in the
      silkworm and Papilio species.

PMID- 27720071
TI  - Color vision and color formation in dragonflies.
AB  - Dragonflies including damselflies are colorful and large-eyed insects, which show
      remarkable sexual dimorphism, color transition, and color polymorphism. Recent
      comprehensive visual transcriptomics has unveiled an extraordinary diversity of
      opsin genes within the lineage of dragonflies. These opsin genes are
      differentially expressed between aquatic larvae and terrestrial adults, as well
      as between dorsal and ventral regions of adult compound eyes. Recent topics of
      color formation in dragonflies are also outlined. Non-iridescent blue color is
      caused by coherent light scattering from the quasiordered nanostructures, whereas
      iridescent color is produced by multilayer structures. Wrinkles or wax crystals
      sometimes enhances multilayer structural colors. Sex-specific and stage-specific
      color differences in red dragonflies is attributed to redox states of ommochrome
      pigments.

PMID- 27720072
TI  - Molecular mechanisms of secondary sexual trait development in insects.
AB  - Secondary sexual traits are those traits other than the primary gametes that
      distinguish the sexes of a species. The development of secondary sexual traits
      occurs when sexually dimorphic factors, that is, molecules differentially
      produced by primary sex determination systems in males and females, are
      integrated into the gene regulatory networks responsible for sexual trait
      development. In insects, these molecular asymmetric factors were always
      considered to originate inside the trait-building cells, but recent work points
      to external factors, such as hormones, as potential candidates mediating
      secondary sexual trait development. Here, we review examples of the different
      molecular mechanisms producing sexually dimorphic traits in insects, and suggest
      a need to revise our understanding of secondary sexual trait development within
      the insect lineage.

PMID- 27720073
TI  - Complex responses of insect phenology to climate change.
AB  - Insect phenologies are changing in response to climate warming. Shifts toward
      earlier seasonal activity are widespread; however, responses of insect phenology
      to warming are often more complex. Many species have prolonged their activity
      periods; others have shown delays. Furthermore, because of interspecific
      differences in temperature sensitivity, warming can increase or decrease
      synchronization between insects and their food plants and natural enemies. Here,
      I review recent findings in three areas-shifts in phenology, changes in
      voltinism, and altered species interactions-and highlight counterintuitive
      responses to warming caused by the particularities of insect life cycles.
      Throughout, I emphasize how an appreciation of the evolutionary processes shaping
      insect life histories is necessary to forecast changes in insect phenology and
      their demographic consequences.

PMID- 27720074
TI  - Can we predict the effects of multiple stressors on insects in a changing
      climate?
AB  - The responses of insects to climate change will depend on their responses to
      abiotic and biotic stressors in combination. We surveyed the literature, and
      although synergistic stressor interactions appear common among insects, the thin
      taxonomic spread of existing data means that more multi-stressor studies and new
      approaches are needed. We need to move beyond descriptions of the effects of
      multiple stressors to a mechanistic, predictive understanding. Further, we must
      identify which stressor interactions, and species' responses to them, are
      sufficiently generalizable (i.e. most or all species respond similarly to the
      same stressor combination), and thus predictable (for new combinations of
      stressors, or stressors acting via known mechanisms). We discuss experimental
      approaches that could facilitate this shift toward predictive understanding.

PMID- 27720075
TI  - The use of occurrence data to predict the effects of climate change on insects.
AB  - Experimental information on the roles played by climatic factors in determining
      the ecology and distribution of insect species is scarce. This has stimulated the
      increasing use of the climatic characteristics of the localities in which the
      species are observed to derive predictions under different climatic scenarios
      (the so called species-distribution models or SDMs). This text reviews the main
      limitations of these correlative models when they are applied to organisms, such
      as insects, that are characterized by a high degree of collector bias and
      incompleteness. It is argued that SDMs must rely solely on presence information,
      rejecting the use of background or pseudoabsences, and that we are not predicting
      the future distribution of a species but exploring the future location of the
      climatic conditions in which a species was observed. The scarcity and bias of the
      available occurrence information in insects as well as our ignorance about the
      non-climatic factors delimiting species ranges forces us to be extremely careful.
      It is therefore desirable to avoid the use of central tendency measures
      reflecting supposed optimum niche conditions because they are particularly
      dependent on the quantity and biases of the occurrence information. The use of
      simple algorithms and procedures aimed at extracting information on environmental
      limits from the available occurrences would be more convenient in this case.

PMID- 27720076
TI  - The fingerprints of global climate change on insect populations.
AB  - Synthesizing papers from the last two years, I examined generalizations about the
      fingerprints of climate change on insects' population dynamics and phenology.
      Recent work shows that populations can differ in response to changes in climate
      means and variances. The part of the thermal niche occupied by an insect
      population, voltinism, plasticity and adaptation to weather perturbations, and
      interactions with other species can all exacerbate or mitigate responses to
      climate change. Likewise, land use change or agricultural practices can affect
      responses to climate change. Nonetheless, our knowledge of effects of climate
      change is still biased by organism and geographic region, and to some extent by
      scale of climate parameter.

PMID- 27720077
TI  - Molecular basis and ecological relevance of aphid body colors.
AB  - Aphids are small phloem sap-feeding insects, and show color polymorphism even
      within the same species. Crossing experiments have revealed the inheritance
      pattern of the body color. Coloration of aphids is determined by mainly three
      pigments, melanin, carotenoid, and aphin, and is influenced by both abiotic and
      biotic environmental factors. Aphid body colors also seem to correspond with
      specific biological functions under various environments. Partly due to the
      presence of natural enemies in the environment, a variety of physiological and
      behavioral responses have evolved in each color form. Thus, predation is one of
      the most significant external factors for maintaining body color polymorphisms.
      In addition, endosymbiont infections also influence aphid body color and prey
      predator interactions. However, many unsolved questions remain regarding the
      molecular basis for and biological functions of aphid body colors. Further work,
      including the development of molecular techniques for comprehensive functional
      analysis, is needed in these areas.

PMID- 27720078
TI  - Mechanistic models for predicting insect responses to climate change.
AB  - Mechanistic models of the impacts of climate change on insects can be seen as
      very specific hypotheses about the connections between microclimate,
      ecophysiology and vital rates. These models must adequately capture stage
      specific responses, carry-over effects between successive stages, and the
      evolutionary potential of the functional traits involved in complex insect life
      cycles. Here we highlight key considerations for current approaches to
      mechanistic modelling of insect responses to climate change. We illustrate these
      considerations within a general mechanistic framework incorporating the
      thermodynamic linkages between microclimate and heat, water and nutrient exchange
      throughout the life-cycle under different climate scenarios. We emphasise how
      such a holistic perspective will provide increasingly robust insights into how
      insects adapt and respond to changing climates.

PMID- 27720079
TI  - Will climate change affect insect pheromonal communication?
AB  - Understanding how climate change will affect species interactions is a challenge
      for all branches of ecology. We have only limited understanding of how increasing
      temperature and atmospheric CO2 and O3 levels will affect pheromone-mediated
      communication among insects. Based on the existing literature, we suggest that
      the entire process of pheromonal communication, from production to behavioural
      response, is likely to be impacted by increases in temperature and modifications
      to atmospheric CO2 and O3 levels. We argue that insect species relying on long
      range chemical signals will be most impacted, because these signals will likely
      suffer from longer exposure to oxidative gases during dispersal. We provide
      future directions for research programmes investigating the consequences of
      climate change on insect pheromonal communication.

PMID- 27720080
TI  - A call to insect scientists: challenges and opportunities of managing insect
      communities under climate change.
AB  - As climate change moves insect systems into uncharted territory, more knowledge
      about insect dynamics and the factors that drive them could enable us to better
      manage and conserve insect communities. Climate change may also require us to
      revisit insect management goals and strategies and lead to a new kind of
      scientific engagement in management decision-making. Here we make five key points
      about the role of insect science in aiding and crafting management decisions, and
      we illustrate those points with the monarch butterfly and the Karner blue
      butterfly, two species undergoing considerable change and facing new management
      dilemmas. Insect biology has a strong history of engagement in applied problems,
      and as the impacts of climate change increase, a reimagined ethic of entomology
      in service of broader society may emerge. We hope to motivate insect biologists
      to contribute time and effort toward solving the challenges of climate change.

PMID- 27720081
TI  - Evolutionary and ecological patterns of thermal acclimation capacity in
      Drosophila: is it important for keeping up with climate change?
AB  - Phenotypic plasticity of temperature tolerance (thermal acclimation) is often
      highlighted as an important component of the acute and evolutionary adaptation to
      temperatures in insects. For this reason, it is often suggested that thermal
      acclimation ability could be important for buffering the consequences of climate
      change. Based on data from Drosophila we discuss if and how phenotypic plasticity
      is likely to mitigate the effects of climate change. We conclude that plasticity
      of upper thermal limits is small in magnitude, evolves slowly and that
      acclimation ability is weakly correlated with latitude and environmental
      heterogeneity. Accordingly plasticity in upper thermal limits is unlikely to
      effectively buffer effects of global warming for species already close to their
      upper thermal boundaries.

PMID- 27720082
TI  - Editorial overview: Global change biology: Linking pattern and process to
      prediction and policy.

PMID- 27720083
TI  - Editorial overview: Molecular physiology: molecular basis of insect colors and
      patterns.

PMID- 27720084
TI  - A Second Trimester Abdominal Ectopic Pregnancy.

PMID- 27720085
TI  - Grossesse extra-uterine abdominale au deuxieme trimestre.

PMID- 27720086
TI  - JOGC and the Future.

PMID- 27720087
TI  - Le Journal d'obstetrique et gynecologie du Canada et l'avenir.

PMID- 27720088
TI  - Association Between Factor V Leiden Mutation, Small for Gestational Age, and
      Preterm Birth: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To estimate the association of a maternal factor V Leiden (FVL)
      mutation with SGA and preterm birth. DATA SOURCES: We performed a search of
      PubMed, Embase, Scopus, CINAHL, and the Cochrane Library from inception to April
      2016 for cohort and case-control studies of women with FVL mutation and
      associated outcomes of SGA and preterm birth that included a reference group
      without FVL mutation. Additional studies were identified from reference lists of
      relevant research and review articles. STUDY SELECTION: Two authors (JKB, AMO)
      independently examined the abstracts of the potentially eligible studies, and
      full texts of eligible studies were retrieved for further evaluation.
      Disagreements were resolved by consensus. We identified 42 studies suitable for
      inclusion in the meta-analysis. DATA EXTRACTION: Thirty-two studies evaluated
      SGA, and 18 studies assessed preterm birth. Study quality was assessed using the
      Newcastle Ottawa Scale. A random effects model with inverse variance weighting
      was used to calculate pooled ORs and 95% CIs. Subgroup analyses were performed by
      study design. DATA SYNTHESIS: The overall OR associating FVL mutation with SGA
      was significant (OR 1.40, 95% CI 1.18 to 1.67). Analysis of 13 cohort studies
      resulted in an OR of 1.20 (95% CI 1.03 to 1.41), and data from 19 case-control
      studies yielded an OR of 1.86 (95% CI 1.35 to 2.56). There was no significant
      association between FVL mutation and preterm birth (OR 1.17, 95% CI 1.00 to 1.37)
      when all groups were studied, but the association was significant for case
      control studies alone (OR 1.40, 95% CI 1.05 to 1.86). CONCLUSION: There is an
      increased risk for SGA in pregnancies complicated by FVL mutation in both cohort
      and case-control study designs. The risk of preterm birth with FVL mutation is
      less clear, although there is conflicting evidence from cohort and case-control
      studies regarding the risk of preterm birth associated with FVL mutation.

PMID- 27720089
TI  - The Usefulness of the APACHE II Score in Obstetric Critical Care: A Structured
      Review.
AB  - OBJECTIVE: To assess the performance of the Acute Physiology and Chronic Health
      Evaluation II (APACHE II) mortality prediction model in pregnant and recently
      pregnant women receiving critical care in low-, middle-, and high-income
      countries during the study period (1985-2015), using a structured literature
      review. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Evidence-Based
      Medicine Reviews, searched for articles published between 1985 and 2015. STUDY
      SELECTION: Twenty-five studies (24 publications), of which two were prospective,
      were included in the analyses. Ten studies were from high-income countries
      (HICs), and 15 were from low- and middle-income countries (LMICs). Median study
      duration and size were six years and 124 women, respectively. DATA SYNTHESIS: ICU
      admission complicates 0.48% of deliveries, and pregnant and recently pregnant
      women account for 1.49% of ICU admissions. One quarter were admitted while
      pregnant, three quarters of these for an obstetric indication and for a median of
      three days. The median APACHE II score was 10.9, with a median APACHE II
      predicted mortality of 16.6%. Observed mortality was 4.6%, and the median
      standardized mortality ratio was 0.36 (interquartile range 0.23 to 0.73). The
      standardized mortality ratio was < 0.9 in 24 of 25 studies. Women in HICs were
      more frequently admitted with a medical comorbidity but were less likely to die
      than were women in LMICs. CONCLUSION: The APACHE II score consistently
      overestimates mortality risks for pregnant and recently pregnant women receiving
      critical care, whether they reside in HICs or LMICs. There is a need for a
      pregnancy-specific outcome prediction model for these women.

PMID- 27720090
TI  - Sex Ratios Among Births in British Columbia, 2000-2013.
AB  - OBJECTIVE: Previous studies have reported distorted sex ratios among live births
      within specific immigrant groups in Canada. We carried out an investigation into
      sex ratios in British Columbia. METHODS: All stillbirths and live births to
      residents of British Columbia from April 2000 to March 2013 were included in the
      study, with data obtained from the British Columbia Perinatal Data Registry. We
      examined sex ratios among births and among pregnancy terminations that resulted
      in a stillbirth or live birth. Analyses were stratified by congenital anomaly
      status, maternal residence, and parity. RESULTS: The study population included
      567 225 stillbirths and live births. In the Fraser Health Authority, the sex
      ratio among births without congenital anomalies was 51.3% males (95% CI 51.1 to
      51.5); this was significantly higher than the sex ratio of 40.7% males (95% CI
      33.2 to 48.6) among late pregnancy terminations without congenital anomalies (P =
      0.008). However, in British Columbia, excluding the Fraser Health Authority, the
      same sex ratios were 51.1% (95% CI 50.9 to 51.3) and 51.1% (95% CI 45.5 to 56.7),
      respectively (P = 0.99). Sex ratios among births to multiparous women were also
      significantly different in the Fraser Health Authority. Only a negligible
      fraction of the shortfall in female births in the Fraser Health Authority could
      be explained by sex ratio distortions among late pregnancy terminations.
      CONCLUSION: Sex ratios among stillbirths and live births to residents of the
      Fraser Health Authority are distorted relative to those observed elsewhere in
      British Columbia. This is likely due to sex differences in early pregnancy
      terminations.

PMID- 27720091
TI  - Ongoing Cases of Early-Onset Group B Streptococcal Disease in the Era of
      Screening and Prophylaxis.
AB  - OBJECTIVE: We reviewed cases of group B Streptococcus (GBS) sepsis in term
      infants at our institution to identify areas for potential prevention. METHODS:
      We identified cases by searching our institution's microbiology databases for all
      positive GBS blood and cerebrospinal fluid cultures taken from infants between
      2008 and 2013. Patients were included if the timing of the positive culture met
      the criteria for early-onset GBS disease (age 7 days or under). Charts that met
      inclusion criteria were abstracted for details related to antepartum screening,
      intrapartum care, and postpartum outcome. RESULTS: There are an average of 10 000
      deliveries per year in our institution. During the five-year period (2008-2013),
      we identified 13 cases representing early-onset GBS disease in term infants. Of
      the 13 cases, nine mothers screened negative for GBS, two screened positive, and
      two were screened unknown. Four cases qualified for intrapartum prophylaxis; of
      these, two did not receive appropriate prophylaxis, one because of parental
      refusal and one for unspecified reasons after the membranes had been ruptured for
      > 18 hours. All 13 infants had confirmed GBS bacteremia, and four had concurrent
      GBS meningitis. One infant died and one infant had neurologic sequelae.
      CONCLUSION: Early-onset GBS disease in term infants continues to occur at our
      institution, and consequences for the infant can be severe. The majority of cases
      identified were screened and managed in accordance with current guidelines. Most
      cases were GBS negative when screened in the antepartum period, raising the
      question of whether a more sensitive test or a test closer to delivery could
      prevent further cases of early-onset GBS disease.

PMID- 27720092
TI  - Evaluating the Postpartum Maternal Health Clinic: How Patient Characteristics
      Predict Follow-Up.
AB  - OBJECTIVE: At Kingston General Hospital, women who have pregnancy-related
      cardiovascular risk indicators (e.g., preeclampsia, gestational hypertension,
      gestational diabetes) are offered standardized six-month postpartum follow-up for
      cardiovascular disease risk screening and counselling. We sought to assess how
      patient characteristics predict attendance at follow-up. METHODS: We undertook a
      chart review of 650 patients who delivered between April 2011 and December 2014
      and had preeclampsia, gestational hypertension, or gestational diabetes. Logistic
      regression was used to analyze the relationship between clinical and demographic
      variables and attendance at the follow-up clinic. RESULTS: Increasing age (in
      years) was significantly correlated with attendance at follow-up (adjusted OR
      [aOR] 1.08, 95% CI 1.04 to 1.12). Women who had preeclampsia were significantly
      more likely to attend than women who had gestational hypertension or gestational
      diabetes (aOR 1.54, 95% CI 1.05 to 2.26). Women who were known to be non-smokers
      or whose smoking status was not recorded were significantly more likely to attend
      follow-up (aOR 2.47, 95% CI 1.32 to 4.62). There was a trend towards lower follow
      up for women from census tracts or subdivisions with a greater proportion of
      individuals without educational certificate, diploma, or degree, but this was not
      statistically significant (aOR 0.10, 95% CI 0.01 to 1.22). CONCLUSION: There is
      significant selection bias among women who attend follow-up for postpartum
      cardiovascular disease risk screening and counselling after pregnancies
      complicated by preeclampsia, gestational hypertension, or gestational diabetes.

PMID- 27720093
TI  - Magnocaine: Physical Compatibility and Chemical Stability of Magnesium Sulphate
      and Lidocaine Hydrochloride in Prefilled Syringes.
AB  - OBJECTIVE: To evaluate the physical compatibility and chemical stability of
      mixtures of magnesium sulphate and lidocaine in order to determine the
      feasibility of manufacturing a prefilled syringe combining these two drugs for
      use as an intramuscular (IM) loading dose for eclampsia prevention and/or
      treatment. This ready-to-use mixture will provide a more tolerable and accessible
      route of administration appropriate for widespread use. METHODS: Physical
      compatibility (pH, colour, and formation of precipitate) and chemical stability
      (maintaining > 90% of initial concentrations) of mixtures of MgSO4, using both
      commercially available MgSO4 (50%) and MgSO4 reconstituted from salt (61%), with
      lidocaine hydrochloride (2%) were evaluated every 14 days over six months. The
      concentration of lidocaine was determined by a stability indicating high
      performance liquid chromatographic method, while the concentration of magnesium
      was determined by an automated chemistry analyzer. RESULTS: No changes in pH,
      color or precipitates were observed for up to 6 months. The 95% confidence
      interval of the slope of the curve relating concentration to time, determined by
      linear regression, indicated that only the admixtures of commercially-available
      magnesium sulfate and lidocaine as well as the 61% magnesium sulfate solution
      (reconstituted from salt) maintained at least 90% of the initial concentration of
      both drugs at 25 degrees C and 40 degrees C at 6 months. CONCLUSIONS:
      Commercially available MgSO4 and lidocaine hydrochloride, when combined, are
      stable in a pre-filled syringe for at least six months in high heat and humidity
      conditions. This finding represents the first step in improving the
      administration of magnesium sulphate in the treatment and prevention of eclampsia
      in under-resourced settings.

PMID- 27720094
TI  - Optimizing Participation of Pregnant Women in Clinical Trials: Factors
      Influencing Decisions About Participation in Medication and Vaccine Trials.
AB  - OBJECTIVE: To obtain information on women's attitudes and opinions about
      participation in vaccine and medication trials during pregnancy. METHODS: A
      quantitative, cross-sectional survey was administered to 110 consenting women
      over a four-week period in the waiting room of an ambulatory obstetrics and
      gynaecology clinic in Ontario. RESULTS: The final response rate was 74.8%, with
      the majority of participants agreeing with statements about the importance of
      obtaining safety data about products in pregnancy and the importance of a woman
      having the ability to choose whether to participate in such research. Of all
      participants, 16.3% indicated they would consider participating in vaccine
      research during pregnancy and 20.0% would consider participating in medication
      research during pregnancy. Factors relating to maternal or fetal/child health
      were the most frequently cited factors influencing willingness to participate,
      with lack of trust in researchers and pharmaceutical companies as factors that
      would discourage participation. CONCLUSION: A minority of pregnant women were
      willing to consider participating in medication or vaccine research during
      pregnancy. Optimizing participation requires providing women (and if appropriate,
      their partners) with detailed, multidisciplinary education about the maternal and
      fetal benefits and risks of such trials. Education about the principles of
      research ethics, including the limits of involvement of pharmaceutical companies,
      would be beneficial.

PMID- 27720095
TI  - Uterine Transplants in the Canadian Setting: A Theoretical Framework.
AB  - The uterine transplant is an innovative surgical procedure whereby a healthy
      uterus is transplanted into a woman with uterine factor infertility (UFI) for the
      purpose of procreation. Twelve uterine transplants have been attempted in the
      world in the last two decades, and five have led to viable births. While uterine
      transplantation is still in its experimental stages, it remains unclear whether
      Canadian centres plan to attempt the procedure in the near future. Herein, I
      raise several observations that are specific to the Canadian setting and apply
      the Montreal Criteria for the Ethical Feasibility of Uterine Transplantation to
      determine whether there is fertile ground for a uterine transplantation program
      to be adopted in Canada.

PMID- 27720096
TI  - Improving Communication in Obstetrics Practice.

PMID- 27720097
TI  - Implications of Applying Minimal Risk Standards in Clinical Research to
      Information Provision in Prenatal and Pre-conception Care.
AB  - BACKGROUND: There have long been minimal risk thresholds beneath which risks may
      not need to be discussed in clinical research. This threshold concept may be
      applied to clinical practice. Our research explored application of minimal risk
      standards in research regulations to providing information in prenatal and pre
      conception care. METHODS: A case study approach applied minimal risk standards in
      research regulations to prenatal and pre-conception care with respect to the
      risks of excess alcohol consumption, folic acid insufficiency, exposure to
      phthalate plasticizers, and exposure to brominated flame retardants (BFRs).
      RESULTS: Excess alcohol consumption and folic acid insufficiency were found to be
      above the minimal risk standards as outlined in research regulations, while
      exposure to phthalates and BFRs requires more evidence to determine whether they
      are above minimal risk. However, applying the minimal risk standard based on the
      daily life of a healthy adult or a fetus in a healthy pregnant woman, phthalates
      and BFRs are at the minimal risk threshold regardless of their potential harm
      since all pregnant women may be exposed to these chemicals in their daily life.
      Nevertheless, if there is demonstration of sufficient evidence of harm, they may
      be above minimal risk if such harm can be reduced by individual choice to avoid
      exposure. CONCLUSION: The minimal risk concept in research regulations as applied
      to clinical practice may be useful to help clinicians and professional
      organizations determine what risks need be discussed in prenatal and pre
      conception care.

PMID- 27720098
TI  - Contrast enhanced ultrasound (CEUS) in the prenatal evaluation of suspected
      invasive placenta percreta.
AB  - BACKGROUND: Morbidly adherent placentation now complicates approximately 1 in 500
      pregnancies. Our group and others have demonstrated that antenatal diagnosis of
      invasive placentation and team-based delivery reduce severe morbidity. Ultrasound
      and magnetic resonance imaging (MRI) are both employed in the antenatal
      evaluation of pregnancies with suspected placenta increta/percreta. Accurate
      diagnosis in this context is essential to direct resources appropriately.
      Ultrasound methods, including colour and power Doppler, are the mainstays of
      screening at-risk women, whereas MRI is reserved for diagnostic purposes because
      of its cost and limited accessibility. In current practice, both methods are
      significantly limited by an inability to accurately define aberrant utero
      placental blood flow, the definitive sign of deeply invasive placentation. We
      describe here an adjunctive method to define aberrant blood flow using
      ultrasound. CASE: We employed contrast-enhanced ultrasound (CEUS) in the
      antenatal evaluation of suspected extensive invasive placentation in a woman at
      18 weeks' gestation. Invasive placentation was confirmed following hysterectomy.
      CONCLUSION: CEUS, a technique that has been established as safe and well
      tolerated in the non-pregnant setting, has the potential to be deployed as a
      powerful adjunct to ultrasound to enhance both the screening and diagnostic
      components of care for women with suspected invasive placentation.

PMID- 27720099
TI  - Isolated Appendiceal Endometriosis.
AB  - BACKGROUND: Pain associated with appendiceal endometriosis can mimic other intra
      abdominal pathology. The diagnosis is usually obvious during gross inspection of
      the appendix; however, the absence of classical macroscopic appearances may lead
      to missed cases in which the patient's pain is misdiagnosed and inappropriately
      managed. CASE: A 34-year-old woman presented with cyclical right iliac fossa pain
      and an elevated serum C-reactive protein of 13 mg/L (normal < 5 mg/L). Diagnostic
      laparoscopy showed an isolated appendiceal mass with no pelvic endometriosis, and
      an appendectomy was performed. Histopathology demonstrated appendiceal
      endometriosis without macroscopic involvement of other pelvic organs. CONCLUSION:
      This case gives insight into the pathophysiology of endometriosis. We advocate
      routine appendectomy in women with unexplained recurrent abdominal pain because a
      diagnostic laparoscopy may miss isolated endometriosis of the appendix, and we
      now have evidence that this may have no external features suggesting the
      diagnosis. Additionally, endometriosis can involve the gastrointestinal tract
      without involvement of the reproductive organs. This is important information in
      the further progression of theories underlying the pathophysiology of
      endometriosis.

PMID- 27720100
TI  - Ultrasound Evaluation of First Trimester Complications of Pregnancy.
AB  - OBJECTIVE: OUTCOMES:: EVIDENCE: A MEDLINE search and review of bibliographies
      identified articles was conducted. VALUES: The evidence collected was reviewed by
      the Diagnostic Imaging Committee of the Society of Obstetricians and
      Gynaecologists of Canada. The recommendations were made according to the
      guidelines developed by The Canadian Task Force on Preventive Health Care (Table
      1). BENEFITS, HARMS, AND COSTS: Women presenting with first trimester bleeding
      may be incorrectly diagnosed with a missed abortion, may have an ectopic
      pregnancy overlooked, or may be inappropriately reassured about viability.
      Improvement in the identification of the sonographic landmarks of normal
      embryonic development and awareness of the sonographic risk factors of pregnancy
      failure may lead to more case-specific management strategies. Diagnosis of
      suspected ectopic pregnancy often involves an assessment of both hormonal markers
      and sonographic features. Maternal morbidity and mortality can be reduced with an
      early diagnosis of ectopic pregnancy. RECOMMENDATIONS: 

PMID- 27720101
TI  - Evaluation echographique des complications au premier trimestre de grossesse.
AB  - OBJECTIFS: ReSULTATS: SOURCES DE DONNeES: Nous avons effectue des recherches dans
      MEDLINE et un examen de la bibliographie des articles recenses. VALEURS: Le
      Comite d'imagerie diagnostique de la Societe des obstetriciens et gynecologues du
      Canada a passe en revue les donnees probantes recueillies. Les recommandations
      reposent sur les lignes directrices elaborees par le Groupe d'etude canadien sur
      les soins de sante preventifs (tableau 1). AVANTAGES, DeSAVANTAGES ET COuTS: Les
      femmes qui presentent des saignements durant le premier trimestre peuvent
      recevoir un diagnostic incorrect d'avortement manque. En outre, on risque de ne
      pas detecter une grossesse ectopique ou de les rassurer a tort sur la viabilite
      de l'embryon. L'amelioration de la detection des reperes echographiques du
      developpement embryonnaire normal et de la connaissance des facteurs de risque
      lies a l'echec de grossesse sur le plan echographique pourrait donner lieu a
      l'elaboration de strategies de prise en charge mieux adaptees a chaque cas. Le
      diagnostic d'une grossesse ectopique suspectee repose souvent sur l'evaluation de
      marqueurs hormonaux et de caracteristiques echographiques. Par ailleurs, le
      diagnostic precoce de grossesse ectopique peut reduire la morbidite et la
      mortalite maternelles. RECOMMANDATIONS.

PMID- 27720102
TI  - SNEB 2016 Conference Translates Principles of Next Practice Into Action.

PMID- 27720103
TI  - Wandering Around in the Grocery Stores.

PMID- 27720104
TI  - Qualitative Analysis of Dietary Behaviors in Picture Book Fiction for 4- to 8
      Year-Olds.
AB  - OBJECTIVE: Picture books may facilitate parents' efforts to decrease pickiness
      and other undesirable food habits in children. This study conducted a content
      analysis of dietary behaviors and feeding strategies featured in fictional
      picture books compared with those discussed in the research literature. DESIGN:
      Several databases were searched for fictional picture books about dietary
      behavior, published between 2000 and 2016, accessible in the US, available in
      print format, and designated for 4- to 8-year-olds. PHENOMENON OF INTEREST:
      Messages about dietary behavior in picture book fiction. ANALYSIS: Stories were
      systematically coded using holistic, data-driven, and evaluation coding methods.
      The final set of codes was examined for themes and patterns. RESULTS: Of the 104
      books, 50% featured a specific eating behavior, 21% lifestyle/eating patterns,
      20% food-related sensations and emotions, and 9% table manners. CONCLUSIONS AND
      IMPLICATIONS: Books about dietary behaviors are abundant but the topic coverage
      is unbalanced. Problem behaviors portrayed in books overlap those discussed in
      the research literature. However, problem-solving strategies and actions do not
      align with those endorsed by nutrition professionals. Messages vary in their
      complexity (in terms of their plot and/or language), ranging from clear and
      direct to vague, sophisticated, unresolved, conflicting, or controversial.
      Recommendations for practitioners are discussed.

PMID- 27720106
TI  - Erratum.

PMID- 27720105
TI  - A Systematic Review of the Impact of Multi-Strategy Nutrition Education Programs
      on Health and Nutrition of Adolescents.
AB  - OBJECTIVE: To update evidence on the impact of multi-strategy nutrition education
      interventions on adolescents' health and nutrition outcomes and behaviors.
      DESIGN: Systematic review of randomized controlled studies of multi-strategy
      interventions encompassing nutrition education published from 2000 to 2014 guided
      by the Preferred Reported Items for Systematic Reviews and Meta-analyses
      statement. SETTING: Secondary schools in developed countries. PARTICIPANTS:
      Adolescents aged 10-18 years. MAIN OUTCOME MEASURES: Anthropometric and dietary
      intake. ANALYSIS: Systematic search of 7,009 unduplicated articles and review of
      11 studies (13 articles) meeting inclusion criteria using qualitative comparison.
      RESULTS: Four studies reported significant changes in anthropometric measures and
      9 showed significant changes in dietary intake. Type of nutrition education
      varied. Components of the interventions that showed statistically significant
      changes in anthropometric and dietary intake included facilitation of the
      programs by school staff and teachers, parental involvement, and using
      theoretical models to guide the intervention's development. Changes in canteens,
      food supply, and vending machines were associated with significant changes in
      dietary intake. CONCLUSIONS AND IMPLICATIONS: Multi-strategy interventions can
      have significant impacts on nutrition of adolescents when the nutrition education
      is theoretically based and facilitated by school staff in conjunction with
      parents and families, and includes changes to the school food environment.

PMID- 27720107
TI  - Nutrition Education Resources in North Carolina-Based Head Start Preschool
      Programs: Administrator and Teacher Perceptions of Availability and Use.
AB  - OBJECTIVE: The purpose of this study was to provide new insight into common
      barriers to the availability and use of nutrition education (NE) resources in
      Head Start preschool programs based on administrator and teacher perceptions.
      METHODS: In-depth, semistructured phone interviews (n = 63) were conducted with
      administrators (n = 31) and teachers (n = 32) from North Carolina-based Head
      Start programs. Interviews were audio-recorded and transcribed verbatim. Data
      were analyzed qualitatively using content analysis to identify common themes.
      RESULTS: Five emergent themes were identified within the areas of NE resource
      availability and use and barriers to NE resource availability and use.
      Participants expressed desire for greater organization of existing NE material
      resources, increased community support, and professional development
      opportunities for teachers specific to NE. Funding and time constraints were
      reported as affecting NE resources. CONCLUSIONS AND IMPLICATIONS: Creative
      strategies for addressing NE resource availability and use and barriers (eg, NE
      integration with educational standards) in Head Start are needed.

PMID- 27720108
TI  - The Prevalence of Food Security and Insecurity Among Illinois University
      Students: Reporting the Strength of Association.

PMID- 27720109
TI  - The Prevalence of Food Security and Insecurity Among Illinois University Students
      Response Letter.

PMID- 27720111
TI  - A Great Era Comes to an End: And a New One Begins!

PMID- 27720112
TI  - Development of chemical isotope labeling liquid chromatography mass spectrometry
      for silkworm hemolymph metabolomics.
AB  - Silkworm (Bombyx mori) is a very useful target insect for evaluation of endocrine
      disruptor chemicals (EDCs) due to mature breeding techniques, complete endocrine
      system and broad basic knowledge on developmental biology. Comparative
      metabolomics of silkworms with and without EDC exposure offers another dimension
      of studying EDCs. In this work, we report a workflow on metabolomic profiling of
      silkworm hemolymph based on high-performance chemical isotope labeling (CIL)
      liquid chromatography mass spectrometry (LC-MS) and demonstrate its application
      in studying the metabolic changes associated with the pesticide
      dichlorodiphenyltrichloroethane (DDT) exposure in silkworm. Hemolymph samples
      were taken from mature silkworms after growing on diet that contained DDT at four
      different concentrations (1, 0.1, 0.01, 0.001 ppm) as well as on diet without DDT
      as controls. They were subjected to differential 12C-/13C-dansyl labeling of the
      amine/phenol submetabolome, LC-UV quantification of the total amount of labeled
      metabolites for sample normalization, and LC-MS detection and relative
      quantification of individual metabolites in comparative samples. The total
      concentration of labeled metabolites did not show any significant change between
      four DDT-treatment groups and one control group. Multivariate statistical
      analysis of the metabolome data set showed that there was a distinct metabolomic
      separation between the five groups. Out of the 2044 detected peak pairs, 338 and
      1471 metabolites have been putatively identified against the HMDB database and
      the EML library, respectively. 65 metabolites were identified by the dansyl
      library searching based on the accurate mass and retention time. Among the 65
      identified metabolites, 33 positive metabolites had changes of greater than 1.20
      fold or less than 0.83-fold in one or more groups with p-value of smaller than
      0.05. Several useful biomarkers including serine, methionine, tryptophan,
      asymmetric dimethylarginine, N-Methyl-D-aspartic and tyrosine were identified.
      The changes of these biomarkers were likely due to the disruption of the
      endocrine system of silkworm by DDT. This work illustrates that the method of CIL
      LC-MS is useful to generate quantitative submetabolome profiles from a small
      volume of silkworm hemolymph with much higher coverage than conventional LC-MS
      methods, thereby facilitating the discovery of potential metabolite biomarkers
      related to EDC or other chemical exposure.

PMID- 27720113
TI  - A dual-response fluorescent probe for Zn2+ and Al3+ detection in aqueous media:
      pH-dependent selectivity and practical application.
AB  - A Schiff base-type fluorescent probe (1) consist of 2-hydroxynaphthaldehyde and
      glutamide moieties has been designed and synthesized for detection Zn2+ and Al3+.
      The probe shows pH dependent dual-selectivity for Zn2+ and Al3+ in Tris-HCl
      buffer, viz. that can selectively recognized Zn2+ at pH 7.4 and Al3+ at pH 6.0,
      respectively. From Job's plots and MS data, the stoichiometric ratios of the
      probe with Zn2+ and Al3+ appeared to be 1:1 and 2:1, respectively. The probe can
      detect as low as 5.5 * 10-8 M-1 Zn2+ and 1.27 * 10-7 M-1 Al3+, whereas respective
      association constants are 4.27 * 104 M-1 and 3.50 * 109 M-1. Furthermore, it is
      also confirmed that the probe has good cell-permeability and could thus be used
      to selectively sense intracellular Zn2+ and Al3+ by bioimaging in different pH
      environment. Finally the probe has been used successfully for determination of
      the analytes in real drug samples.

PMID- 27720114
TI  - Synthesizing a nano-composite of BSA-capped Au nanoclusters/graphitic carbon
      nitride nanosheets as a new fluorescent probe for dopamine detection.
AB  - A strong red fluorescent nanocomposite, consisting of graphite-like carbon
      nitride nanosheets (g-C3N4 NSs) and serum albumin-capped Au nanoclusters (AuNCs),
      was synthesized. Dopamine (DA) can quench the red fluorescence of the
      nanocomposite, based on the Forster resonance energy transfer (FRET) mechanism.
      In this quenching process, the energy is transferred from the fluorescent g-C3N4
      NSs-AuNCs to the oxidized DA quinine molecules (DA is easily oxidated to form DA
      quinine in air). The red fluorescence emission at 420 nm decreases dramatically
      and the quenching ratio (F0 - F)/F0 is linearly related to the concentration of
      DA in the range of 0.05-8.0 MUmol L-1 with a detection limit of 0.018 MUmol L-1
      (S/N = 3). Additionally, this sensor has a potential of application to assay the
      DA in the real samples, such as human serum and human urine.

PMID- 27720115
TI  - A review of oxyhalide disinfection by-products determination in water by ion
      chromatography and ion chromatography-mass spectrometry.
AB  - This paper is a review of ion chromatographic (IC) separations of inorganic
      oxyhalide disinfection by-products (DBPs) in water and beverages. The review
      outlines the chemical mechanisms of formation, regulation of maximum allowable
      levels, chromatographic column selection and speciation. In addition, this review
      highlights the application of IC coupled to mass spectrometry (MS) for trace and
      elemental composition analysis of oxyhalides, along with the analytical
      considerations associated to enable sensitive analysis. Furthermore, a review of
      literature concerning IC determination of inorganic oxyhalide DBPs in
      environmental matrices, including water, published since 2005 is presented, with
      a focus on MS detection, and a discussion on the relative performance of the
      methods. Finally some prospective areas for future research, including fast,
      selective, multi-analyte analysis, for this application are highlighted and
      discussed.

PMID- 27720117
TI  - Electrophoretic stacking for sensitive determination of antibiotic ceftazidime in
      human blood and microdialysates from diabetic foot.
AB  - An electrophoretic stacking method has been developed for monitoring the
      therapeutic level of the antibiotic ceftazidime in blood plasma and
      microdialysates taken from peripheral soft tissues of the lower limbs of patients
      with diabetic foot syndrome. The biological samples are treated by addition of
      acetonitrile in an amount of 75% v/v and injected into a capillary in a large
      volume; after turning on the separation voltage, the residual acetonitrile is
      forced out of the capillary by the application of hydrodynamic pressure. The
      clinical samples were separated in an optimised background electrolyte composed
      of 50 mM chloroacetic acid +20% v/v methanol +0.5% v/v INST coating solution. The
      attained LOD for ceftazidime equalled 0.42 MUg mL-1 (0.8 MUM) and the migration
      time equalled 3.75 min when using a 25 MUm capillary with minimum length of 31.5
      cm. The separation was controlled by a maximum voltage of +30 kV and the movement
      of the analyte was accelerated by a pressure of 50 mbar. The RSD values for intra
      day repeatability of the migration time and peak area are 0.14% and 3.8%,
      respectively; the inter-day values equalled 0.25% for the migration time and 7.3%
      for peak area, respectively. Pharmacological studies revealed that ceftazidime
      passes from the blood circulation to the peripheral tissues of the lower limbs
      with an efficiency of 20%. The introduction of CE control of ceftazidime level in
      diabetic foot represents a very important improvement in achieving the targeted
      therapeutic effect.

PMID- 27720116
TI  - Multi-residue analysis of pesticides, plant hormones, veterinary drugs and
      mycotoxins using HILIC chromatography - MS/MS in various food matrices.
AB  - One of the recent trends in Analytical Chemistry is the development of economic,
      quick and easy hyphenated methods to be used in a field that includes analytes of
      different classes and physicochemical properties. In this work a multi-residue
      method was developed for the simultaneous determination of 28 xenobiotics (polar
      and hydrophilic) using hydrophilic interaction liquid chromatography technique
      (HILIC) coupled with triple quadrupole mass spectrometry (LC-MS/MS) technology.
      The scope of the method includes plant growth regulators (chlormequat,
      daminozide, diquat, maleic hydrazide, mepiquat, paraquat), pesticides
      (cyromazine, the metabolite of the fungicide propineb PTU (propylenethiourea),
      amitrole), various multiclass antibiotics (tetracyclines, sulfonamides
      quinolones, kasugamycin and mycotoxins (aflatoxin B1, B2, fumonisin B1 and
      ochratoxin A). Isolation of the analytes from the matrix was achieved with a fast
      and effective technique. The validation of the multi-residue method was performed
      at the levels: 10 MUg/kg and 100 MUg/kg in the following representative
      substrates: fruits-vegetables (apples, apricots, lettuce and onions), cereals and
      pulses (flour and chickpeas), animal products (milk and meat) and cereal based
      baby foods. The method was validated taking into consideration EU guidelines and
      showed acceptable linearity (r >= 0.99), accuracy with recoveries between 70 and
      120% and precision with RSD <= 20% for the majority of the analytes studied. For
      the analytes that presented accuracy and precision values outside the acceptable
      limits the method still is able to serve as a semi-quantitative method. The
      matrix effect, the limits of detection and quantification were also estimated and
      compared with the current EU MRLs (Maximum Residue Levels) and FAO/WHO MLs
      (Maximum Levels) or CXLs (Codex Maximum Residue Limits). The combined and
      expanded uncertainty of the method for each analyte per substrate, was also
      estimated.

PMID- 27720118
TI  - Titanium dioxide nanoparticle coating of polymethacrylate-based chromatographic
      monoliths for phosphopetides enrichment.
AB  - Metal oxide affinity chromatography has been one of the approaches for specific
      enrichment of phosphopeptides from complex samples, based on specific
      phosphopeptide adsorption forming bidentate chelates between phosphate anions and
      the surface of a metal oxide, such as TiO2, ZrO2, Fe2O3, and Al2O3. Due to
      convective mass transfer, flow-independent resolution and high dynamic binding
      capacity, monolith chromatographic supports have become important in studies
      where high resolution and selectivity are required. Here, we report the first
      synthesis and characterization of immobilisation of rutile TiO2 nanoparticles
      onto organic monolithic chromatographic support (CIM-OH-TiO2). We demonstrate the
      specificity of CIM-OH-TiO2 column for enrichment of phosphopeptides by studying
      chromatographic separation of model phosphorylated and nonphosphorylated peptides
      as well as proving the phosphopeptide enrichment of digested bovine alpha-casein.
      The work described here opens the possibility for a faster, more selective
      enrichment of phosphopeptides from biological samples that will enable future
      advances in studying protein phosphorylation.

PMID- 27720119
TI  - Tutorial on estimating the limit of detection using LC-MS analysis, part I:
      Theoretical review.
AB  - A large body of literature exists on the limit of detection (LOD), but there is
      still a lot of confusion about this important validation parameter. This
      confusion mainly stems from its statistically complex background. The goal of
      this two-part tutorial is to discuss and clarify the topic of LOD for
      practitioners. The two main conclusions of this tutorial are: (1) the choice of
      how to estimate LOD should be based on the purpose of the analytical method that
      is being validated (e.g. considerable effort should not be made to estimate LOD
      for a method that is not used for detecting traces in the vicinity of LOD), and
      (2) LOD estimates are strongly dependent on different assumptions and the
      approach used, and therefore caution must be exercised when using the estimate or
      when comparing different estimates. Part I of the tutorial contains a theoretical
      discussion (without excessively sophisticated statistics) and part II contains
      examples based on experimental data. In Part I, LOD and other definitions related
      to it are reviewed, and their estimation and use are discussed. The assumptions
      and practicality of different approaches to estimate LOD are compared. Different
      aspects of the analytical method that strongly influence LOD estimates (e.g.
      linearity, scedasticity and day-to-day variability of LOD) together with
      experimental design considerations when estimating LOD are discussed. In part II,
      LOD is estimated for the LC-MS/MS analysis method to detect pesticides on
      separate days. The performance of different tests on the data necessary for LOD
      estimation are discussed and the results of different approaches under review in
      this tutorial are compared. In conclusion, a decision tree is proposed for
      estimating and monitoring LOD. A detailed working procedure for estimating LOD is
      presented. Several topics are pointed out in which further research and
      discussion is needed.

PMID- 27720120
TI  - Tutorial on estimating the limit of detection using LC-MS analysis, part II:
      Practical aspects.
AB  - In part II of this tutorial, the investigated approaches of estimating the limit
      of detection (LOD) are applied to experimental data from LC-MS measurements.
      Important practical aspects specific to LC-MS and related to LOD are reviewed.
      The results of different tests of estimating linearity and scedasticity are
      compared. LOD estimates obtained with different approaches (for both simple
      characterization of the analysis method and accurate interpretation of the
      results) are applied to the data and the obtained values are compared. As a
      conclusion, a decision tree is proposed for estimating LOD for analytical methods
      using the LC-MS technique.

PMID- 27720121
TI  - Rapid quantification of metabolic intermediates in blood by liquid chromatography
      tandem mass spectrometry to investigate congenital lactic acidosis.
AB  - A novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been
      established to quantify metabolic intermediates, including lactate (Lac),
      pyruvate (Pyr), acetoacetate (ACAC) and 3-hydroxybutyrate (3-HB) in blood.
      Samples were deproteinized with methanol-acetonitrile solution, and analytes were
      separated on an adamantyl group-bonded reverse phase column and detected in
      multiple reaction monitoring mode. Total analysis time was 4 min per sample.
      Method validation results displayed that limits of quantification were 10.0 MUmol
      L-1 for Lac and Pyr, and 5.0 MUmol L-1for ACAC and 3-HB. The within- and between
      run coefficients of variation were in the range of 1.2-6.4% for all analytes. The
      recoveries were ranged from 95.6 to 111.5%. The reference values of analytes were
      determined for the pediatric population. Duo to instability of Lac, Pyr and ACAC
      in vitro, a comprehensive stability assay was performed to determine optimal
      conditions for sample collection, pretreatment and storage. Results showed that
      precipitation of protein in blood at bedside combined with low storage
      temperature could effectively preserve the integrity of Lac, Pyr and 3-HB, but
      the precipitated protein accelerated degradation of ACAC. Isolation of
      supernatant fluid slowed degradation of ACAC. Supernatant samples could store at 
      20  degrees C for 10 days. The use of plasma or serum to determine these
      intermediates was not recommended. In this study, 450 samples from patients were
      analyzed, and 7 patients were diagnosed as congenital lactic acidosis. With the
      advantages of rapid, accurate and reliable, this method is very suitable for
      congenital lactic acidosis screening and researches related to energy metabolism.

PMID- 27720122
TI  - Plasma micro-nanotextured polymeric micromixer for DNA purification with high
      efficiency and dynamic range.
AB  - We present a polymeric microfluidic chip capable of purifying DNA through solid
      phase extraction. It is designed to be used as a module of an integrated Lab-on
      chip platform for pathogen detection, but it can also be used as a stand-alone
      device. The microfluidic channels are oxygen plasma micro-nanotextured, i.e.
      randomly roughened in the micro-nano scale, a process creating high surface area
      as well as high density of carboxyl groups (COOH). The COOH groups together with
      a buffer that contains polyethylene glycol (PEG), NaCl and ethanol are able to
      bind DNA on the microchannel surface. The chip design incorporates a mixer so
      that sample and buffer can be efficiently mixed on chip under continuous flow.
      DNA is subsequently eluted in water. The chip is able to isolate DNA with high
      recovery efficiency (96+/- 11%) in an extremely large dynamic range of
      prepurified Salmonella DNA as well as from Salmonella cell lysates that
      correspond to a range of 5 to 1.9 * 108 cells (0.263 fg to 2 * 500 ng). The chip
      was evaluated via absorbance measurements, polymerase chain reaction (PCR), and
      gel electrophoresis.

PMID- 27720123
TI  - Colorimetric detection of proteins based on target-induced activation of
      aptazyme.
AB  - The detection of protein is vital to fundamental research as well as practical
      applications. However, most detection methods depend on antibody-based assays
      which are faced with many shortcomings. Herein, we propose a colorimetric method
      for protein assays based on target-triggered activation of aptazyme, which may
      offer simple, rapid and cost-effective detection of the target protein. In this
      method, the conformation change of aptazyme induced by target protein is designed
      to be associated with aptazyme activation. Consequently, in the presence of the
      target protein, the designed DNA linkers will be cleaved into two fragments that
      fail to cross-link gold nanoparticles (GNPs), thus the color of GNP solution
      remains red, while the color will be changed in the absence of the target.
      Because of the advantages of aptazyme such as economic synthesis, stable, easy
      modification and its ability to accomplish signal recognition and signal
      amplification simultaneously, the method is thermostable, simple and cost
      efficient. In this work, we have taken the detection of vascular endothelial
      growth factor (VEGF) as an example, which can present an analytical performance
      with as low as 0.1 nM detection limit, spanning a detection range of 3 orders of
      magnitude. What is more, the principle of this proposed new method can be
      extended as a universal assay method not only for the detection of analytes which
      have an aptamer but also for those analytes that have ligands.

PMID- 27720124
TI  - Enhanced sensing of dengue virus DNA detection using O2 plasma treated-silicon
      nanowire based electrical biosensor.
AB  - Dengue Virus (DENV) has become one of the most serious arthropod-borne viral
      diseases, causing death globally. The existing methods for DENV detection suffer
      from the late stage treatment due to antibodies-based detection which is feasible
      only after five days following the onset of the illness. Here, we demonstrated
      the highly effective molecular electronic based detection utilizing silicon
      nanowire (SiNW) integrated with standard complementary metal-oxide-semiconductor
      (CMOS) process as a sensing device for detecting deoxyribonucleic acid (DNA)
      related to DENV in an early stage diagnosis. To transform the fabricated devices
      as a functional sensing element, three-step procedure consist of SiNW surface
      modification, DNA immobilization and DNA hybridization were employed. The
      detection principle works by detecting the changes in current of SiNW which
      bridge the source and drain terminal to sense the immobilization of probe DNA and
      their hybridization with target DNA. The oxygen (O2) plasma was proposed as an
      effective strategy for increasing the binding amounts of target DNA by modified
      the SiNW surface. It was found that the detection limit of the optimized O2
      plasma treated-SiNW device could be reduced to 1.985 * 10-14 M with a linear
      detection range of the sequence-specific DNA from 1.0 * 10-9 M to 1.0 * 10-13 M.
      In addition, the developed biosensor device was able to discriminate between
      complementary, single mismatch and non-complementary DNA sequences. This highly
      sensitive assay was then applied to the detection of reverse transcription
      polymerase chain reaction (RT-PCR) product of DENV-DNA, making it as a potential
      method for disease diagnosis through electrical biosensor.

PMID- 27720125
TI  - One-pot synthesis of strongly fluorescent DNA-CuInS2 quantum dots for label-free
      and ultrasensitive detection of anthrax lethal factor DNA.
AB  - Herein, high quality DNA-CuInS2 QDs are facilely synthesized through a one-pot
      hydrothermal method with fluorescence quantum yield as high as 23.4%, and the
      strongly fluorescent DNA-CuInS2 QDs have been utilized as a novel fluorescent
      biosensor for label-free and ultrasensitive detection of anthrax lethal factor
      DNA. L-Cysteine (L-Cys) and a specific-sequence DNA are used as co-ligands to
      stabilize the CuInS2 QDs. The specific-sequence DNA consists of two domains:
      phosphorothiolates domain (sulfur-containing variants of the usual phosphodiester
      backbone) controls the nanocrystal passivation and serves as a ligand, and the
      functional domain (non-phosphorothioates) controls the biorecognition. The as
      prepared DNA-CuInS2 QDs have high stability, good water-solubility and low
      toxicity. Under the optimized conditions, a linear correlation was established
      between the fluorescence intensity ratio I/I0 (I0 is the original fluorescence
      intensity of DNA-CuInS2 QDs, and I is the fluorescence intensity of DNA-CuInS2
      QDs/GO with the addition of various concentrations of anthrax lethal factor DNA)
      and the concentration of anthrax lethal factor DNA in the range of 0.029-0.733
      nmol L-1 with a detection limit of 0.013 nmol L-1. The proposed method has been
      successfully applied to the determination of anthrax lethal factor DNA sequence
      in human serum samples with satisfactory results. Because of low toxicity and
      fine biocompatibility, DNA-CuInS2 QDs also hold potential applications in
      bioimaging.

PMID- 27720126
TI  - Colorimetric assay for on-the-spot alcoholic strength sensing in spirit samples
      based on dual-responsive lanthanide coordination polymer particles with
      ratiometric fluorescence.
AB  - This study demonstrates a new strategy for colorimetric detection of alcoholic
      strength (AS) in spirit samples based on dual-responsive lanthanide infinite
      coordination polymer (Ln-ICP) particles with ratiometric fluorescence. The ICP
      used in this study are composed of two components: one is the supramolecular Ln
      ICP network formed by the coordination between the ligand 2,2'-thiodiacetic acid
      (TDA) and central metal ion Eu3+; and the other is a fluorescent dye, i.e.,
      coumarin 343 (C343), both as the cofactor ligand and as the sensitizer, doped
      into the Ln-ICP network through self-adaptive chemistry. Upon being excited at
      300 nm, the red fluorescence of Ln-ICP network itself at 617 nm is highly
      enhanced due to the concomitant energy transfer from C343 to Eu3+, while the
      fluorescence of C343 at 495 nm is supressed. In pure ethanol solvent, the as
      formed C343@Eu-TDA is well dispersed and quite stable. However, the addition of
      water into ethanolic dispersion of C343@Eu-TDA destructs Eu-TDA network
      structure, resulting in the release of C343 from ICP network into the solvent.
      Consequently, the fluorescence of Eu-TDA turns off and the fluorescence of C343
      turns on, leading to the fluorescent color change of the dispersion from red to
      blue, which constitutes a new mechanism for colorimetric sensing of AS in
      commercial spirit samples. With the method developed here, we could clearly
      distinguish the AS of different spirit samples within a wide linear range from
      10% vol to 100% vol directly by "naked eye" with the help of UV-lamp (365 nm).
      This study not only offers a new method for on-the-spot visible detection of AS,
      but also provides a strategy for dual-responsive sensing mode by rational
      designing the optical properties of the Ln-ICP network and the guest,
      respectively.

PMID- 27720127
TI  - Measuring heterogeneity of reinjury risk assessments at the time of clearance to
      return to play: A feasibility study.
AB  - OBJECTIVES: Different individuals may make different return to play (RTP)
      decisions due to different risk assessments or risk tolerances. Our objectives
      were to determine the feasibility of eliciting reinjury risk assessments with
      Bayesian methods, and risk tolerance with questionnaires, from clinicians and
      athletes in a real-world RTP setting. DESIGN: Feasibility study with a
      descriptive prospective case-series. METHODS: We recruited the athlete, sport
      physician and physiotherapist caring for an athlete ("triplet") within on-going
      groin and hamstring injury studies. We applied Bayesian methods to elicit
      estimates for reinjury risk over the next 2 months, based on the available
      clinical knowledge, and projected activity level. We used a standardized
      questionnaire to elicit factors affecting risk tolerance. RESULTS: Although our
      methods appeared feasible in general, there were important challenges that
      included language, time availability of practicing clinicians, and general work
      flow issues related to embedding our study within an on-going larger study. We
      did obtain valuable data from more than one person on 10 of the 15 eligible
      athletes recruited. Despite the limited number of cases, there were clinically
      meaningful differences in risk estimates in some cases. In one triplet,
      participants estimated the reinjury risk between 1-10%, 20-50% and 30-40% for the
      same athlete. The most common factors modifying risk tolerance were "timing and
      season", "pressure from athlete", and "external pressure". CONCLUSIONS: Bayesian
      methods for risk elicitation in clinical sport medicine are feasible, and large
      differences in both risk estimation and risk tolerance sometimes occur.

PMID- 27720128
TI  - Deviation from goal pace, body temperature and body mass loss as predictors of
      road race performance.
AB  - OBJECTIVES: The purpose of this study was to examine the relationship between
      pacing, gastrointestinal temperature (TGI), and percent body mass loss (%BML) on
      relative race performance during a warm weather 11.3km road race. DESIGN:
      Observational study of a sample of active runners competing in the 2014 Falmouth
      Road Race. METHODS: Participants ingested a TGI pill and donned a GPS enabled
      watch with heart rate monitoring capabilities prior to the start of the race.
      Percent off predicted pace (%OFF) was calculated for seven segments of the race.
      Separate linear regression analyses were used to assess the relationship between
      pace, TGI, and %BML on relative race performance. One-way ANOVA was used to
      analyse post race TGI (>=40 degrees C vs <40 degrees C) on pace and %OFF.
      RESULTS: Larger %BML was associated with faster finish times (R2=0.19, p=0.018),
      faster average pace (R2=0.29, p=0.012), and a greater %OFF (R2=0.15, p=0.033).
      %OFF during the first mile (1.61km) significantly predicted overall finish time
      (R2=0.64, p<0.001) while %OFF during the second mile (3.22km) (R2 change=0.18,
      p<0.001) further added to the model (R2=0.82, p<0.001). Body temperature (pre
      race TGI and post race TGI) was not predictive of overall finish time (p>0.05).
      There was a trend in a slower pace (p=0.055) and greater %OFF (p=0.056) in
      runners finishing the race with a TGI>40 degrees C. CONCLUSIONS: Overall, finish
      time was influenced by greater variations in pace during the first two miles of
      the race. In addition, runners who minimized fluid losses and had lower TGI were
      associated with meeting self-predicted goals.

PMID- 27720130
TI  - Black:white disparities in breast cancer mortality in the 50 largest cities in
      the United States, 2005-2014.
AB  - INTRODUCTION: This paper presents race-specific breast cancer mortality rates and
      the corresponding rate ratios for the 50 largest U.S. cities for each of the 5
      year intervals between 2005 and 2014. METHODS: The 50 largest cities in the U.S.
      were the units of analysis. Numerator data were abstracted from national death
      files where the cause was malignant neoplasm of the breast (ICD-10=C50) for
      women. Population-based denominators were obtained from the U.S. Census Bureau
      for 2010-2014. To measure the racial disparity, we calculated Black:White rate
      ratios (RRs) and confidence intervals for each 5-year period. To determine
      whether changes over time in the disparity were statistically significant, we
      calculated a 2-sided z score for the change in the relative percent difference
      between the Black and White rates for 2005-2009 and 2010-2014. RESULTS: At the
      most recent time point (2010-2014), the RR was significantly greater than 1.00 in
      the US and 24 cities. The change in the Black:White disparity was statistically
      significant in five cities and the US. The percent difference increased
      significantly in Atlanta, GA (from 4.1 to 117.4, p<0.001); San Antonio, TX (from
      24.4 to 79.3, p=0.034); and the US (from 39.7 to 43.1, p=0.007). The percent
      difference decreased significantly in Memphis, TN (from 111.0 to 68.9, p=0.043);
      Philadelphia, PA (from 43.1 to 23.5, p=0.049); and Boston, MA (from 48.9 to 0.7,
      p=0.022). CONCLUSION: This analysis provides updated city-level breast cancer
      mortality data for Black and White women through 2014, and reveals that in the US
      and 24 of the 43 largest US cities, Black women continue to die from breast
      cancer at a higher rate than their White counterparts. Importantly, however, a
      few cities, Memphis, Boston and Philadelphia, showed a decrease in the
      Black:White breast cancer mortality disparity between 2005-2009 and 2010-2014.

PMID- 27720129
TI  - Increased acute mortality with chemoradiotherapy for locally advanced head and
      neck cancer in patients >=70years.
AB  - PURPOSE: Concurrent chemoradiotherapy (CRT) is the standard of care for many
      sites of locally advanced head and neck squamous cell carcinomas (LAHNC).
      However, on meta-analysis, the addition of chemotherapy did not improve survival
      for patients >70years. We hypothesized that elderly patients treated with CRT
      would have increased toxicity without similar improvements in survival. METHODS:
      A single-institution, IRB-approved retrospective study took place from 2005 to
      2012 including 369 patients treated with CRT for LAHNC. Multivariate models for
      death at 3months and death over time were developed using logistic regression and
      Cox modeling, respectively. RESULTS: Patients >=70years were treated less often
      with concurrent cisplatin dosed every 3weeks (25.5% vs. 71.4%, respectively) and
      more often with weekly carboplatin (31.9% vs. 3.4%) than patients <70years
      (n=322; p<0.001). Patients >=70years experienced increased toxicity during
      treatment with more frequently hospitalizations (36.2% vs. 21.1%; p=0.02) and a
      lower rate of PEG removal at last follow-up or death (77.1% vs. 92.9%; p=0.004).
      A higher proportion of patients >=70years died within 3months (12.8% vs. 2.8%;
      p=0.001) following CRT. Patients >=70 had an increased risk of death at 3months
      following CRT (odds ratio 5.19, 95% CI 1.64-16.41; p=0.005) and worse survival
      over time (hazard ratio 2.30, 95% CI 1.34-3.93; p=0.002). CONCLUSIONS: Patients
      >=70years were more often treated with less toxic chemotherapy, yet experienced
      higher rates of hospitalization during treatment and increased rates of acute
      mortality following CRT. The efficacy of chemoradiotherapy for elderly patients
      should be evaluated in a prospective setting.

PMID- 27720131
TI  - Disseminated Histiocytic Sarcoma in an African Hedgehog (Atelerix albiventris).
AB  - Disseminated histiocytic sarcoma (HS) was diagnosed on post-mortem examination of
      a 1.5-year-old African hedgehog (Atelerix albiventris) that was presented in poor
      physical condition and with diarrhoea. Leucocytosis and a hypoechoic abdominal
      mass were noted on haematological and ultrasonographical examinations. Gross
      pathological, histopathological, immunohistochemical and ultrastructural
      evaluation of the mass supported a diagnosis of disseminated HS. To our
      knowledge, this report represents the first documentation of disseminated HS in
      this species.

PMID- 27720132
TI  - Sex specific influence on the relationship between maternal exposures to
      persistent chemicals and birth outcomes.
AB  - Prenatal exposure to persistent pollutants has been associated with adverse birth
      outcomes, although few studies have investigated the influence of the sex of the
      infant. Sex specific differences have been associated with neurobehavioural
      impacts from environmental exposures with limited and contrary findings in
      relation to persistent pollutants. This study investigated the relationships
      between maternal exposure to a range of metals, polychlorinated biphenyls and
      pesticides measured in biological samples and birth outcomes with a specific
      focus on the sex of the infant. Outcome measures used included birth weight,
      birth length and head circumference, proportion of optimal birth weight (POBW),
      proportion of optimal birth length, proportion of optimal head circumference
      (POHC) and ponderal index. In general maternal urinary and blood metals, plasma
      polychlorinated biphenyl and pesticide concentrations were low. In adjusted
      regression models, a ln-unit increase in plasma beta-hexachlorocyclohexane
      concentrations was associated with decreased birth weight (-76g, 95% CI -149, 
      33), ponderal index (-0.048, 95% CI 0.102, 0.007) and proportion of optimal birth
      weight (-1.5%, 95% CI -3.6, 0.5) in the whole study population, with stronger
      associations observed for male infants. Maternal p,p'
      dichlorodiphenyldichloroethylene concentrations were associated with reduced
      ponderal index in male infants (beta=-0.171, 95% CI -0.269, -0.074). A ln-unit
      increase in plasma hexachlorobenzene concentrations was associated with a 5%
      increase in POBW in male infants (95% CI 0.67, 9.5). Increased urinary barium was
      associated with increased birth length and POBL and decreased ponderal index in
      boys. Conversely, urinary concentrations of caesium and rubidium were found to be
      associated with decreased foetal growth in female infants. This study supports
      the growing body of evidence regarding the reductions in foetal growth associated
      with beta-hexachlorocyclohexane and p,p'-Dichlorodiphenyldichloroethylene as well
      as reporting new relationships between metals exposures and birth outcomes. The
      finding that maternal exposure to barium, strontium, rubidium and caesium was
      associated with birth outcomes requires confirmation in larger studies. Similarly
      the apparent differences in susceptibility based on sex of the infant requires
      further investigation.

PMID- 27720133
TI  - Assessing the impact of sanitation on indicators of fecal exposure along
      principal transmission pathways: A systematic review.
AB  - OBJECTIVE: Fecal-oral transmission of enteric and other pathogens due to poor
      sanitation is a major cause of morbidity and mortality, especially in low- or
      middle-income settings. Few studies have investigated the impact of sanitation on
      indicators of transmission, a prerequisite to achieving health gains. This review
      attempts to summarize the literature to date. METHODS: We searched leading
      databases to identify studies that address the effect of sanitation on various
      transmission pathways including fecal pathogens or indicator bacteria in drinking
      water, hand contamination, sentinel toys, food, household and latrine surfaces
      and soil, as well as flies and observations of human feces. This also included
      studies that assessed the impact of fecal contamination of water supplies based
      on distance from sanitation facilities. We identified 29 studies that met the
      review's eligibility criteria. RESULTS AND CONCLUSION: Overall, the studies found
      little to no effect from sanitation interventions on these transmission pathways.
      There was no evidence of effects on water quality (source or household), hand or
      sentinel toy contamination, food contamination, or contamination of surfaces or
      soil. There is some evidence that sanitation was associated with reductions in
      flies and a small effect on observations of feces (Risk Difference -0.03, 95%CI 
      0.06 to 0.01). Studies show an inverse relationship between the distance of a
      water supply from a latrine and level of fecal contamination of such water
      supply. Future evaluations of sanitation interventions should include assessments
      of effects along transmission pathways in order to better understand the
      circumstances under which interventions may be effective at preventing disease.

PMID- 27720134
TI  - L-plastin regulates the stability of the immune synapse of naive and effector T
      cells.
AB  - T-cells need to be tightly regulated during their activation and effector phase
      to assure an appropriate defence against cancer or pathogens and - vice versa -
      to avoid autoimmune reactions. Regulatory signals are provided via the immune
      synapse between T-cells and antigen-presenting cells (APCs) or target cells. The
      stability and kinetics of immune synapse formation is critical for proper T-cell
      functions. It requires dynamic rearrangements of the actin cytoskeleton necessary
      for organized spatio-temporal redistribution of receptors and adhesion molecules.
      We identified glucocorticoid-sensitive phosphorylation of serine 5 on the actin
      bundling protein L-plastin as one important signalling event for this regulation.
      Using imaging flow cytometry as well as confocal and super-resolution microscopy
      we showed that L-plastin relocalizes to the immune synapse upon antigen
      encounter, where it associates with the beta2-subunit of LFA-1 (CD11a/CD18).
      Interfering with L-plastin expression or activation leads to a defective LFA-1
      recruitment and unstable T-cell/APC contacts. Consequently, the lack of L-plastin
      diminishes T-cell activation, proliferation and proximal effector responses such
      as cytokine production. On the other hand, a pro-oxidative milieu leads to
      prolonged activation of L-plastin resulting in a stronger enrichment of LFA-1 in
      the cytolytic immune synapse. Concomitant stabilization of conjugates formed by
      cytotoxic T-cells (CTLs) and their target cells impairs the ability of CTLs to
      kill more than one target cells (serial killing), which de facto leads to a
      downregulation of T-cell cytotoxicity. Together, we demonstrate that activation
      and spacial distribution of L-plastin regulates the maturation and stability of
      activating and cytolytic immune synapses important for T-cell activation and
      effector functions.

PMID- 27720135
TI  - [Toward a customized preservation for each kidney graft?]
AB  - The increased number of patients in waiting list for renal transplantation
      requires the establishment of recommendations regarding graft preservation
      techniques. The preservation method impacts graft function and survival
      particularly in case of extended criteria donors. Based on our experience, the
      aim of this review is to establish a decisional diagram to draw graft management
      to 5years in relation to donor type and graft quality. Novel biomarkers are
      necessary to evaluate graft quality. Nuclear magnetic resonance or transcriptomic
      analyses are promising. Thus, good quality organs will be preserved in static
      condition associated to hypothermia; while grafts from extended criteria donors
      need to be assessed early during dynamic perfusion through an evaluation of
      perfusion solution to discriminate: good organs, with acceptable risks without
      perfusion conditions modifications; tolerable risk grafts for which it will be
      recommended to use a supplementation of perfusion solution with oxygen or
      pharmacologic additives such as mitochondrion protectors or oxygen carriers; and
      elevated risks graft which will not be used. This diagram based on experimental
      data needs to be assessed in clinical trials but highlights the crucial role of
      kidney graft quality assessment for its management and placed dynamic perfusion
      preservation as the protocol of choice for extended criteria donors.

PMID- 27720136
TI  - IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as
      first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): a
      multicentre, open-label, randomised, controlled, phase 3 trial.
AB  - BACKGROUND: In a phase 2 study in patients with metastatic renal cell carcinoma,
      overall survival was associated with T-cell responses against IMA901, a vaccine
      consisting of ten tumour-associated peptides. In this phase 3 trial, we aimed to
      determine the clinical effect of adding IMA901 to sunitinib, the standard first
      line treatment in metastatic renal cell carcinoma with postulated favourable
      immunomodulatory effects. METHODS: The IMPRINT study is an open-label,
      randomised, controlled, phase 3 trial done at 124 clinical sites in 11 countries.
      HLA-A*02-positive patients (aged >=18 years) with treatment-naive, histologically
      confirmed metastatic or locally advanced (or both) clear-cell renal cell
      carcinoma were randomly assigned (3:2) to receive sunitinib plus up to ten
      intradermal vaccinations of IMA901 (4.13 mg) and granulocyte macrophage colony
      stimulating factor (75 MUg), with one dose of cyclophosphamide (300 mg/m2) 3 days
      before the first vaccination, or to receive sunitinib alone. Sunitinib (50 mg)
      was given orally once daily, with each cycle defined as 4 weeks on treatment
      followed by 2 weeks off treatment, until progression of disease as determined by
      the investigator, death, or withdrawal of consent. Block randomisation (block
      size five) was done centrally using an interactive web response system,
      stratified by prognostic risk, geographical region, and previous nephrectomy.
      Patients and investigators were not masked to treatment allocation. The primary
      endpoint was overall survival from randomisation until death of any cause as
      determined by the investigator, analysed by intention to treat. This study is
      registered with ClinicalTrials.gov, number NCT01265901. FINDINGS: Between Dec 22,
      2010, and Dec 15, 2012, we screened 1171 patients, of whom 339 were randomly
      assigned to receive sunitinib plus IMA901 (n=204) or sunitinib monotherapy
      (n=135). Patients had a median follow-up of 33.27 months (IQR 29.92-35.64).
      Median overall survival did not differ significantly between the groups (33.17
      months [95% CI 27.81-41.36] in the sunitinib plus IMA901 group vs not reached
      [33.67-not reached] in the sunitinib monotherapy group; hazard ratio 1.34 [0.96
      1.86]; p=0.087). 116 (57%) of 202 patients in the sunitinib plus IMA901 group and
      62 (47%) of 132 in the sunitinib group had grade 3 or worse adverse events, the
      most common of which were hypertension, neutropenia, and anaemia in both groups,
      and mild-to-moderate transient injection-site reactions (eg, erythema, pruritus)
      were the most frequent IMA901-related side-effect in the sunitinib plus IMA901
      group. Serious adverse events leading to death occurred in four (2%) patients
      (one respiratory failure and circulatory collapse [possibly related to
      sunitinib], one oesophageal varices haemorrhage [possibly related to sunitinib],
      one cardiac arrest [possibly related to sunitinib], and one myocardial
      infarction) and eight (6%) patients in the sunitinib group (one case each of
      renal failure, oesophageal varices haemorrhage, circulatory collapse, wound
      infection, ileus, cerebrovascular accident [possibly treatment related], and
      sepsis). INTERPRETATION: IMA901 did not improve overall survival when added to
      sunitinib as first-line treatment in patients with metastatic renal cell
      carcinoma. The magnitude of immune responses needs to be improved before further
      development of IMA901 in this disease is indicated. FUNDING: Immatics
      Biotechnologies.

PMID- 27720137
TI  - Vaccine therapy in renal cell carcinoma: attempting to leap over a rising bar.

PMID- 27720138
TI  - Physics of metabolic organization.
AB  - We review the most comprehensive metabolic theory of life existing to date. A
      special focus is given to the thermodynamic roots of this theory and to
      implications that the laws of physics-such as the conservation of mass and energy
      have on all life. Both the theoretical foundations and biological applications
      are covered. Hitherto, the foundations were more accessible to physicists or
      mathematicians, and the applications to biologists, causing a dichotomy in what
      always should have been a single body of work. To bridge the gap between the two
      aspects of the same theory, we (i) adhere to the theoretical formalism, (ii) try
      to minimize the amount of information that a reader needs to process, but also
      (iii) invoke examples from biology to motivate the introduction of new concepts
      and to justify the assumptions made, and (iv) show how the careful formalism of
      the general theory enables modular, self-consistent extensions that capture
      important features of the species and the problem in question. Perhaps the most
      difficult among the introduced concepts, the utilization (or mobilization) energy
      flow, is given particular attention in the form of an original and considerably
      simplified derivation. Specific examples illustrate a range of possible
      applications-from energy budgets of individual organisms, to population dynamics,
      to ecotoxicology.

PMID- 27720139
TI  - Patient portals and health apps: Pitfalls, promises, and what one might learn
      from the other.
AB  - Widespread use of health information technology (IT) could potentially increase
      patients' access to their health information and facilitate future goals of
      advancing patient-centered care. Despite having increased access to their health
      data, patients do not always understand this information or its implications, and
      digital health data can be difficult to navigate when displayed in a small
      format, complex interface. In this paper, we discuss two forms of patient-facing
      health IT tools-patient portals and applications (apps)-and highlight how,
      despite several limitations of each, combining high-yield features of mobile
      health (mHealth) apps with portals could increase patient engagement and self
      management and be more effective than either of them alone. Patient portal
      adoption is variable, and due to design and interface limitations and health
      literacy issues, many people find the portal difficult to use. Conversely, apps
      have experienced rapid adoption and traditionally have more consumer-friendly
      features with easy log-in access, real-time tracking, and simplified data
      display. These features make the applications more intuitive and easy-to-use than
      patient portals. While apps have their own limitations and might serve different
      purposes, patient portals could adopt some high-yield features and functions of
      apps that lead to engagement success with patients. We thus suggest that to
      improve user experience with future portals, developers could look towards
      mHealth apps in design, function, and user interface. Adding new features to
      portals may improve their use and empower patients to track their overall health
      and disease states. Nevertheless, both these health IT tools should be subjected
      to rigorous evaluation to ensure they meet their potential in improving patient
      outcomes.

PMID- 27720141
TI  - Harnessing Integrated Vector Management for Enhanced Disease Prevention.
AB  - The increasing global threat of emerging and re-emerging vector-borne diseases
      (VBDs) poses a serious health problem. The World Health Organization (WHO)
      recommends integrated vector management (IVM) strategy for combating VBD
      transmission. An IVM approach requires entomological knowledge, technical and
      infrastructure capacity, and systems facilitating stakeholder collaboration. In
      sub-Saharan Africa, successful operational IVM experience comes from relatively
      few countries. This article provides an update on the extent to which IVM is
      official national policy, the degree of IVM implementation, the level of
      compliance with WHO guidelines, and concordance in the understanding of IVM, and
      it assesses the operational impact of IVM. The future outlook encompasses
      rational and sustainable use of effective vector control tools and inherent
      improved return for investment for disease vector control.

PMID- 27720140
TI  - Disease Centered Around Calcified Taenia solium Granuloma.
AB  - Taenia solium (the pork tapeworm) is present in most developing countries, where
      it is a frequent cause of seizures and other neurological disease. Parasitic
      larvae invade the human brain, establish, and eventually resolve, leaving a
      calcified scar. While these lesions are common in endemic regions, and most of
      these are clinically silent, a proportion of individuals with calcified
      cysticerci develop seizures from these lesions, and 30-65% of these cases are
      associated with perilesional edema (PE), likely due to host inflammation. This
      manuscript summarizes the importance, characteristics, natural history, and
      potential prevention and treatments of symptomatic calcified neurocysticercosis
      (NCC).

PMID- 27720143
TI  - Sodium and potassium intake in South Africa: an evaluation of 24-hour urine
      collections in a white, black, and Indian population.
AB  - Limited number of studies on salt intake has been conducted in the South Africa.
      The present study established the sodium and potassium excretion (24-hour urine
      collection) of three different South African populations. In total, 692
      successful 24-hour urine collections were analyzed for sodium, potassium, and
      iodine levels. The median sodium and potassium excretion was 122.9 and 33.5
      mmol/d, respectively, and the median salt intake was 7.2 g/d. The majority
      (92.8%) of the population did not meet the recommended potassium intake/d, and
      65.6% consumed more than 6 g of salt/d. Potassium excretion showed a linear
      relationship with salt intake (P-trend <= .001). The median sodium-to-potassium
      ratio was 3.5. These findings support the South African government's sodium
      reduction legislation, as well as global initiatives. More consideration should
      be given to promoting the intake of potassium-rich foods, as this may have a
      greater public health impact than focusing only on dietary sodium reduction.

PMID- 27720142
TI  - Patient characteristics associated with greater blood pressure control in a
      randomized trial of home blood pressure telemonitoring and pharmacist management.
AB  - This paper reports subgroup analysis of a successful cluster-randomized trial to
      identify attributes of hypertensive patients who benefited more or less from an
      intervention combining blood pressure (BP) telemonitoring and pharmacist
      management. The end point was BP < 140/90 mm Hg at 6-month follow-up. Fourteen
      baseline patient characteristics were selected a priori as subgroup variables.
      Among the 351 trial participants, 44% were female, 84% non-Hispanic white, mean
      age was 60.9 years, and mean BP was 149/86 mm Hg. The overall adjusted odds ratio
      for BP control in the intervention versus usual care group was 3.64 (P < .001).
      The effect of the intervention was significantly larger in patients who were
      younger (interaction P = .02), did not have diabetes (P = .005), had high
      baseline diastolic BP (P = .02), added salt less than daily in food preparation
      (P = .007), and took 0-2 (rather than 3-6) antihypertensive medication classes at
      baseline (P = .02). These findings may help prioritize patients for whom the
      intervention is most effective.

PMID- 27720144
TI  - A new cichlid fish in the Sahara: The Ounianga Serir lakes (Chad), a biodiversity
      hotspot in the desert.
AB  - In the rare perennial bodies of water of the Sahara desert, only a few fish
      species have survived to increasing aridification since the end of the last humid
      period at the Holocene, approximately 5000 years BP. Here, I report the
      occurrence of an undescribed haplochomine cichlid fish in Lake Boukou, one of the
      seven Ounianga Serir lakes (Chad). These lakes are located in one of the most
      arid areas of the Sahara desert, but they persist by virtue of subsurface inflow
      of fresh groundwater from a large fossil aquifer. Astatotilapia tchadensis sp.
      nov. is characterized by a black bar between eye and corner of mouth, rounded
      orange spots on anal fin, scales ctenoid, lower limb of first gill arch with 7-8
      gill rackers, dorsal fin with 13-14 spines and 9-11 soft rays, anal fin with 3
      spines and 8-9 soft rays, 29 or 30 lateral line scales, and lower pharyngeal
      dentition with enlarged molariform teeth. The new species is easily distinguished
      from A. desfontainii and A. flaviijosephii, the northernmost haplochromine
      species currently isolated from its other group members, and appears close to an
      unnamed species of Lake Chad basin. Ounianga Serir lakes and especially Lake
      Boukou present a remarkable diversity of fish, the highest known in the Sahara
      desert with a total of at least six fish species belonging to six genera and
      three families. They also constitute an exceptional natural landscape inscribed
      on the UNESCO world heritage list in 2012 and a biodiversity hotspot for desert
      vertebrate species.

PMID- 27720145
TI  - Archaeobotanical reconstructions of vegetation and report of mummified apple
      seeds found in the cellar of a first-century Roman villa on Elba Island.
AB  - In the late Roman Republic period (2nd-1st century BC), in the area of San
      Giovanni on Elba Island, previously subject to intense extraction of iron ore, a
      rustic villa was established by Marco Valerio Messalla, a supreme Roman
      magistrate. The foundations of the walls were discovered and excavated by an
      archaeological mission. Palaeobotanical analysis of a set of stratigraphic layers
      was performed. Palynological slides showed remains of palynomorphic and non
      pollen objects, while data combined with anthracological investigations confirmed
      the hypothesis that in the 1st century AD the villa was destroyed by a fire that
      created a compact crust under which were discovered four broken Roman amphorae
      containing about five hundred apple seeds. Comparisons of archaeological and
      fresh seeds from reference collections showed discontinuous morphology except for
      one group of archaeological samples. DNA was isolated from seeds that had well
      preserved embryos in all groups. DNA extracts from archaeological, wild and
      modern domestic seeds (controls) were amplified by PCR and tested with SSR
      molecular markers, followed by genome analysis.

PMID- 27720146
TI  - Short communication: Rumination and feeding behaviors differ between healthy and
      sick dairy cows during the transition period.
AB  - The objectives of this study were: (1) to describe the rumination and feeding
      behavior of freestall-housed Holstein dairy cows in the weeks around parturition,
      and (2) to determine the relationship between postpartum disease and precalving
      rumination and feeding behavior. Eighty cows were enrolled at approximately 2wk
      (18+/-7d, mean +/- standard deviation) before calving. Using automatic monitoring
      systems, rumination and feeding behavior were recorded continuously from 10d
      before until 3wk after calving. Postpartum health checks were performed each day,
      and metritis assessment was conducted 2 times/wk. Blood beta-hydroxybutyrate was
      measured 3 times/week, and cows with >=1.2mmol/L during the first 14d postpartum
      were diagnosed as having subclinical ketosis. The final data set included 64 cows
      in 5 groups: healthy (n=20), metritis (n=18), subclinical ketosis (SCK; n=9),
      metritis+SCK (n=9), and >1 health problem and not included before (MULT, n=8). We
      compared rumination and feeding data between healthy cows and the 4 categories of
      ill animals in each of 4 periods relative to calving: precalving (d -7 to -2),
      period 1 (d 3 to 8 postpartum), period 2 (d 9 to 14 postpartum), and period 3 (d
      15 to 20 postpartum). Cows with SCK spent less time ruminating during the
      precalving period. Compared with healthy cows, those with SCK and metritis+SCK
      had lower dry matter intake during the precalving period and continued to eat
      less until d 14 and d 20 postpartum, respectively. Cows with metritis and MULT
      cows had lower dry matter intake during the first 2wk postpartum. Precalving
      feeding time was lower for SCK, metritis+SCK, and MULT cows compared with healthy
      cows. The difference in feeding time between healthy and metritis+SCK cows had
      disappeared by period 2 and between all health categories except MULT by period
      3. MULT cows visited the feed bins less often and were less often replaced at the
      feed bin throughout all 4 periods of the study. Automatic monitoring of intake
      and rumination showed promise for the detection of health problems after calving.
      We observed differences in precalving rumination and feeding behavior. Further
      research is necessary to better understand the onset of behavioral changes and
      the relationship between rumination and disease.

PMID- 27720147
TI  - Adipose tissue remodeling in late-lactation dairy cows during feed-restriction
      induced negative energy balance.
AB  - Excessive rates of demand lipolysis in the adipose tissue (AT) during periods of
      negative energy balance (NEB) are associated with increased susceptibility to
      disease and limited lactation performance. Lipolysis induces a remodeling process
      within AT that is characterized by an inflammatory response, cellular
      proliferation, and changes in the extracellular matrix (ECMT). The adipose tissue
      macrophage (ATM) is a key component of the inflammatory response. Infiltration of
      ATM-forming cellular aggregates was demonstrated in transition cows, suggesting
      that ATM trafficking and phenotype changes may be associated with disease.
      However, it is currently unknown if ATM infiltration occurs in dairy cows only
      during NEB states related to the transition period or also during NEB-induced
      lipolysis at other stages of lactation. The objective of this study was to
      evaluate changes in ATM trafficking and inflammatory phenotypes, and the
      expression of genetic markers of AT remodeling in healthy late-lactation cows
      during feed restriction-induced NEB. After a 14-d (d -14 to d -1) preliminary
      period, Holstein cows were randomly assigned to 1 of 2 feeding protocols, ad
      libitum (AL) or feed restriction (FR), for 4 d (d 1-4). Caloric intake was
      reduced in FR to achieve a targeted energy balance of -15 Mcal/d of net energy
      for lactation. Omental and subcutaneous AT samples were collected
      laparoscopically to harvest stromal vascular fraction (SVF) cells on d -3 and 4.
      The FR induced a NEB of -14.1+/-0.62 Mcal/d of net energy for lactation, whereas
      AL cows remained in positive energy balance (3.2+/-0.66 Mcal/d of NEL). The FR
      triggered a lipolytic response reflected in increased plasma nonesterified fatty
      acids (0.65+/-0.05 mEq/L on d 4), enhanced phosphorylation of hormone sensitive
      lipase, and reduced adipocyte diameter. Flow cytometry and immunohistochemistry
      analysis revealed that on d 4, FR cows had increased numbers of CD172a+, an ATM
      (M1 and M2) surface marker, cells in SVF that were localized in aggregates.
      However, FR did not alter the number of SVF cells expressing M1 markers (CD14 and
      CD11c) or M2 markers (CD11b and CD163). This finding contrasts with the
      predominately M1 phenotype observed previously in ATM from clinically diseased
      cows. No changes were observed in the expression of ECMT-related or cell
      proliferation markers. In summary, an acute 4-d lipolytic stimulus in late
      lactation dairy cows led to ATM infiltration with minimal changes in inflammatory
      phenotype and no changes in ECMT. These results underscore that physiological
      changes related to parturition, the onset of lactation, extended periods of
      lipolysis, or a combination of these can induce intense AT remodeling with
      enhanced ATM inflammatory phenotype expression that may impair the metabolic
      function of AT in transition dairy cattle.

PMID- 27720148
TI  - Changes in the intestinal bacterial community, short-chain fatty acid profile,
      and intestinal development of preweaned Holstein calves. 2. Effects of
      gastrointestinal site and age.
AB  - The objective of this work was to assess the effects of age and gastrointestinal
      location (rumen vs. colon) on bacterial community diversity and composition, as
      well as short-chain fatty acid profiles of preruminant male Holstein calves on an
      intensive milk replacer feeding program. Thirty-two calves were fed at 2% of
      their body weight (dry matter basis) from d 10 until harvest. Sixteen calves were
      euthanized at 2wk and another 16 at 4wk of age to collect digesta samples from
      the rumen and colon. The rumen and colon bacterial communities of preruminant
      calves showed a similar degree of diversity (i.e., Shannon index) whereas
      composition differed considerably. The colonic bacterial population was
      characterized by dominance of lactic acid bacteria such as Lactobacillus,
      Streptococcus, Enterococcus, and Bifidobacterium. In addition, colonic short
      chain fatty acid and lactic acid concentrations were between 50 and 850% higher
      than in the rumen, indicating greater fermentative activity in the colon. On the
      other hand, in the rumen, no genus over-dominated and more variation was present
      among calves. Because of an active reticular groove and low starter grain intake
      during the first 1 to 3wk of life, ruminal fermentation may not contribute to
      significant metabolizable energy supply until after 4wk of life in intensively
      fed calves. Until then, calf hindgut fermentation, characterized by high
      abundance of lactic acid bacteria along with increased lactate and butyrate
      concentrations, could be beneficial for intestinal health and survival of the
      calf during the first weeks of life.

PMID- 27720149
TI  - Determination of ultra-low milk fat content using dual-wavelength ultraviolet
      spectroscopy.
AB  - A precise determination of milk fat content in dairy products is of great
      practical importance. Several studies have reported methods to determine the milk
      fat content in commercial dairy products. However, very few of them validated or
      tested cases where the fat milk fat content was ultra-low. Here we present an
      approach to determine ultra-low milk fat content. This method involves extracting
      milk fat using n-heptane and determining its content using dual-wavelength UV
      spectroscopy. The results showed that milk fat at ultra-low concentrations (i.e.,
      as low as 0.148 g/L) could be extracted completely and quantified accurately
      using the proposed approach. This method is reproducible and sufficiently
      precise. We expect that this method can be adapted by industries to determine
      ultra-low concentration of fat in milk and other dairy products with confidence.

PMID- 27720150
TI  - Changes in the intestinal bacterial community, short-chain fatty acid profile,
      and intestinal development of preweaned Holstein calves. 1. Effects of prebiotic
      supplementation depend on site and age.
AB  - Digestive disorders are common during the first few weeks of life of newborn
      calves. Prebiotics are nondigestible but fermentable oligosaccharides that
      modulate growth and activity of beneficial microbial populations, which can
      result in enhanced gut health and function. Galactooligosaccharides (GOS) have
      demonstrated such prebiotic potential. In this study, the effect of GOS
      supplementation on intestinal bacterial community composition and fermentation
      profiles; intestinal health, development, and function; and growth was evaluated
      in dairy calves fed for high rates of growth. Eighty male Holstein calves were
      assigned either to a control treatment consisting of commercial milk replacer or
      to a GOS-rich (i.e., 3.4% of dry matter) milk replacer treatment. After 2 and
      4wk, 8 calves per treatment were slaughtered at each age. Samples of intestinal
      digesta and tissue were collected for assessment of bacterial communities, short
      chain fatty acid concentrations, in vitro measurement of nutrient transport and
      permeability, histomorphology, and gastrointestinal organ size. The remaining 48
      calves continued to wk 8 to measure body growth, nutrient intake, and fecal and
      respiratory scores. Calves fed GOS displayed greater Lactobacillus and
      Bifidobacterium relative abundance and more developed intestinal epithelial
      structures, but also had greater fecal scores presumably related to greater
      colonic water secretion. Control calves showed slightly better growth and milk
      dry matter intake. Size of intestinal organs, intestinal nutrient transport, and
      epithelium paracellular resistance were not affected by treatment. Excessive GOS
      supplementation had both prebiotic and laxative effects, which led to slightly
      lower growth performance while promoting commensal bacteria population and
      greater intestinal epithelium growth.

PMID- 27720152
TI  - Genetic and phenotypic analysis of daily Israeli Holstein milk, fat, and protein
      production as determined by a real-time milk analyzer.
AB  - The objective was to test the hypothesis that more frequent but less accurately
      analyzed milk components may give a more representative measure of a cow's total
      lactation production. Daily records for milk production and fat and protein
      concentration collected by the AfiLab recording system (Afimilk, Kibbutz Afikim,
      Israel) from January 2014 to January 2016 from 47 large kibbutz (communal) herds
      distributed throughout Israel with a total of 37,486 Israeli Holstein cows were
      compared with the same statistics derived from monthly test day records derived
      by Bentley and Foss milk analyzers at the central laboratory of the Israel Cattle
      Breeders Association. The lactation means for all traits were quite similar for
      the 2 methods in both parities, except for fat production, which was lower for
      the daily records. This finding corresponded to fat lactation curves, which
      showed that daily results were lower with low days in milk (DIM) but almost equal
      to the monthly results after 125 DIM. Relative to monthly records, daily records
      overestimated protein percentage before 150 DIM and underestimated protein
      percentage in the second half of the lactation. The standard deviation for first-
      and second-parity daily records scored by the monthly and daily system were least
      similar for fat percentage, but even for this trait the difference was no more
      than 0.1 percentage points. The standard deviations for complete lactation
      production were slightly lower for the daily results for all traits but protein
      production. First-parity heritabilities were higher for lactations computed from
      daily records for all traits except for protein percentage, but differences were
      not significant. For daily records, coefficients of determination to predict
      future milk, fat, and protein lactation production from truncated lactations were
      greatest and root mean squared errors were least if the mean production from the
      last 2 weeks before the truncation date was used to estimate future production.
      Daily first-parity partial lactations for milk, fat, and protein production with
      <150 DIM predicted future lactation more accurately than corresponding monthly
      partial lactations. With only 30 DIM, genetic correlations between predicted and
      actual lactations ranged from 0.73 to 0.79 for milk, fat, and protein production.
      Real-time daily recording of fat and protein concentration by the daily recording
      system may be preferable to monthly analysis for herd-management decisions and
      genetic evaluation. Further study is required to compare the results of
      individual cows in multiple lactations.

PMID- 27720151
TI  - Predicting the distribution of whey protein fouling in a plate heat exchanger
      using the kinetic parameters of the thermal denaturation reaction of beta
      lactoglobulin and the bulk temperature profiles.
AB  - Fouling of plate heat exchangers (PHE) is a severe problem in the dairy industry,
      notably because the relationship between the build-up of protein fouling deposits
      and the chemical reactions taking place in the fouling solution has not yet been
      fully elucidated. Experiments were conducted at pilot scale in a corrugated PHE,
      and fouling deposits were generated using a model beta-lactoglobulin (beta-LG)
      fouling solution for which the beta-LG thermal denaturation reaction constants
      had been previously determined experimentally. Then 18 different bulk temperature
      profiles within the PHE were imposed. Analysis of the fouling runs shows that the
      dry deposit mass per channel versus the ratio R=kunf/kagg (with kunf and kagg
      representing, respectively, the unfolding and aggregation rate constants computed
      from both the identification of the beta-LG thermal denaturation process and
      knowledge of the imposed bulk temperature profile into the PHE channel) is able
      to gather reasonably well the experimental fouling mass data into a unique master
      curve. This type of representation of the results clearly shows that the heat
      induced reactions (unfolding and aggregation) of the various beta-LG molecular
      species in the bulk fluid are essential to capture the trend of the fouling mass
      distribution inside a PHE. This investigation also illustrates unambiguously that
      the release of the unfolded beta-LG (also called beta-LG molten globule) within
      the bulk fluid (and the absence of its consumption in the form of aggregates) is
      a key phenomenon that controls the extent of protein fouling as well as its
      location inside the PHE.

PMID- 27720153
TI  - Short communication: Genetic variation in choice consistency for cows accessing
      automatic milking units.
AB  - Dairy cows milked in automatic milking systems (AMS) with more than 1 milking box
      may, as individuals, have a preference for specific milking boxes if allowed free
      choice. Estimates of quantitative genetic variation in behavioral traits of
      farmed animals have previously been reported, with estimates of heritability
      ranging widely. However, for the consistency of choice in dairy cows, almost no
      published estimates of heritability exist. The hypothesis for this study was that
      choice consistency is partly under additive genetic control and partly controlled
      by permanent environmental (animal) effects. The aims of this study were to
      obtain estimates of genetic and phenotypic parameters for choice consistency in
      dairy cows milked in AMS herds. Data were obtained from 5 commercial Danish herds
      (I-V) with 2 AMS milking boxes (A, B). Milking data were only from milkings where
      both the present and the previous milkings were coded as completed. This filter
      was used to fulfill a criterion of free-choice situation (713,772 milkings, 1,231
      cows). The lactation was divided into 20 segments covering 15d each, from 5 to
      305d in milk. Choice consistency scores were obtained as the fraction of milkings
      without change of box [i.e., 1.0 - u(box change)] for each segment. Data were
      analyzed for one part of lactation at a time using a linear mixed model for first
      parity cows alone and for all parities jointly. Choice consistency was found to
      be only weakly heritable (heritability=0.02 to 0.14) in first as well as in later
      parities, and having intermediate repeatability (repeatability coefficients=0.27
      to 0.56). Heritability was especially low at early and late lactation states.
      These results indicate that consistency, which is itself an indication of
      repeated similar choices, is also repeatable as a trait observed over longer time
      periods. However, the genetic background seems to play a smaller role compared
      with that of the permanent animal effects, indicating that consistency could also
      be a learned behavior. We concluded that consistency in choices are quantifiable,
      but only under weak genetic control.

PMID- 27720154
TI  - Characterization of Escherichia coli and other Enterobacteriaceae in producer
      distributor bulk milk.
AB  - The current study was undertaken to characterize Escherichia coli and other
      Enterobacteriaceae in raw and pasteurized producer-distributor bulk milk (PDBM).
      A total of 258 samples were collected from purchase points in 8 provinces in
      South Africa. The samples were tested for antibiotic residues, phosphatase, total
      aerobic bacteria, coliforms, and E. coli counts. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry was used for
      identification of isolates. Escherichia coli isolates were characterized for
      virulence factors, antimicrobial resistance, serotypes, and presumptive E. coli
      O157:H7. Antibiotic residues and alkaline phosphatase were detected in 2% of both
      raw and pasteurized PDBM (n=258) and 21% pasteurized PDBM (n=104) samples,
      respectively. A total of 729 isolates belonging to 21 genera and 59 species were
      identified. Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, and
      Raoultella ornithinolytica were the most abundant species. Spoilage
      Enterobacteriaceae species exceeded 50% of the total isolates. Escherichia coli
      was detected and isolated from 36% of the milk samples. Thirty-one E. coli
      isolates harbored virulence genes stx1/stx2 and 38% (n=121) were presumptive
      O157:H7. The prevalence of samples with presumptive shigatoxin producing E. coli
      was 10%. Antimicrobial-resistant E. coli isolates were detected in 70% of the
      milk samples with 36% of stx1/stx2 positive E. coli showing multi-drug
      resistance. Information obtained from the study will be used for modeling the
      public health risk posed by milkborne pathogens in PDBM, which in many cases is
      consumed by poor and vulnerable members of the population.

PMID- 27720155
TI  - Physiological predictors of ovulation and pregnancy risk in a fixed-time
      artificial insemination program.
AB  - The objective of this study was to determine the relative importance and
      contribution of several physiological factors as predictors of pregnancy risk in
      an Ovsynch (GnRH-1 - 7d - PGF2alpha - 56h - GnRH-2 - 16h - artificial
      insemination) timed artificial insemination program: (1) age of the corpus luteum
      (CL; original CL, new CL, or both in response to GnRH-1) and resulting
      progesterone concentrations as they affected luteolysis, ovulation after GnRH-2,
      and pregnancy risk; (2) progesterone concentration before GnRH-1 and GnRH-2 on
      subsequent ovulatory response to GnRH-1 and GnRH-2 as well as pregnancy risk; and
      (3) a combination of these factors in a multivariable logistic regression model
      to predict pregnancy risk. Original data from 7 published studies were combined
      including ovulatory responses to both GnRH injections, blood progesterone
      concentrations before GnRH-1, before PGF2alpha, and at 48h after PGF2alpha,
      pregnancy per artificial insemination at d 32 and 60 after artificial
      insemination, and intervening pregnancy loss. Ovulation outcomes were greater at
      lesser progesterone concentrations after both GnRH injections despite the fact
      that pregnancy outcomes were greatest when progesterone exceeded 3ng/mL before
      GnRH-1 and PGF2alpha, suggesting that greater progesterone concentration before
      GnRH-1 and incidence of ovulation act via different mechanisms to improve
      subsequent fertility. Ovulation after GnRH-2 and subsequent pregnancy outcome
      were positively related to lesser concentrations of progesterone at 48h after
      PGF2alpha; however, for maximal pregnancy outcome, progesterone should be
      <0.5ng/mL. Cows with a CL that also formed a new CL after GnRH-1 had the greatest
      pregnancy outcome, whereas cows with only a new CL (i.e., anovulatory cows and
      those at or near estrus without a CL at GnRH-1) had the poorest pregnancy
      outcome. Pregnancy loss was not affected by CL status during the timed artificial
      insemination program. Receiver operator curves produced cut points of
      progesterone concentration that predicted ovulation and pregnancy risk. Selected
      cut points of progesterone concentration 48h after PGF2alpha produced true
      positive risks greater than 90% and false positive risks less than 25%, thus
      demonstrating the high predictability of ovulation after GnRH-2 and subsequent
      pregnancy outcome based on progesterone concentration. We conclude that
      progesterone concentration is highly predictive of ovulation and pregnancy risk
      in addition to body condition, size of ovulatory follicle, and parity.

PMID- 27720156
TI  - Identification of factors influencing teat dip efficacy trial results by meta
      analysis.
AB  - Two meta-analyses were conducted using data from peer-reviewed natural exposure
      (NE) and experimental challenge (EC) teat dip efficacy trials to identify factors
      influencing the new intramammary infection (IMI) rate. A NE data set containing
      16 studies and an EC data set containing 21 studies were created. New IMI rate
      was calculated based on the percentage of new quarter infections per month
      (PNQI/mo) for each observation, in both data sets, and used as the dependent
      variable for model derivation. A linear, mixed-effects model with a random study
      effect, weighted by number of quarters eligible for infection, was derived for
      each data set. The final NE model included the effects of experimental design
      (split herd or split udder), mastitis pathogen group (Staphylococcus aureus,
      Streptococcus agalactiae, environmental streptococci, gram-negative species,
      Corynebacterium spp., or coagulase-negative staphylococci), postmilking treatment
      (iodine, chlorhexidine, linear dodecyl benzene sulfonic acid, chlorine compounds,
      phenol compounds, or undipped negative controls), and the interaction between
      mastitis pathogen group and postmilking treatment. Overall, Corynebacterium spp.
      had the highest new IMI rate (0.0139+/-0.0018 PNQI/mo), and environmental
      streptococci and gram-negative species had the lowest (0.0023+/-0.0022 PNQI/mo).
      Additionally, trials utilizing a split herd experimental design had a 2-fold
      higher new IMI rate than trials using a split udder design. The final EC model
      included the effects of mastitis pathogen (Staph. aureus and Strep. agalactiae),
      postmilking treatment (iodine, chlorine compounds, "other" active ingredients, or
      undipped negative controls), geographic region of study (Eastern, Southern, and
      Pacific Northwest), and the 2-way interactions of region and pathogen group and
      postmilking treatment and pathogen group. Overall, Staph. aureus and Strep.
      agalactiae had similar new IMI rates. Quarters dipped postmilking in either
      iodine (0.0127+/-0.0099 PNQI/mo), chlorine compounds (0.0258+/-0.0095 PNQI/mo),
      or "other" active ingredient teat dips (0.0263+/-0.0106 PNQI/mo) had lower new
      IMI rates than undipped quarters (0.0859+/-0.0087 PNQI/mo). These results
      indicate that experimental design influences the new IMI rate of teat dip
      efficacy trials and that using an effective postmilking teat dip has a greater
      effect on controlling the new Staph. aureus and Strep. agalactiae IMI rate than
      the teat dip's active ingredient.

PMID- 27720157
TI  - Substantial replacement of lactose with fat in a high-lactose milk replacer diet
      increases liver fat accumulation but does not affect insulin sensitivity in veal
      calves.
AB  - In veal calves, the major portion of digestible energy intake originates from
      milk replacer (MR), with lactose and fat contributing approximately 45 and 35%,
      respectively. In veal calves older than 4 mo, prolonged high intakes of MR may
      lead to problems with glucose homeostasis and insulin sensitivity, ultimately
      resulting in sustained insulin resistance, hepatic steatosis, and impaired animal
      performance. The contribution of each of the dietary energy sources (lactose and
      fat) to deteriorated glucose homeostasis and insulin resistance is currently
      unknown. Therefore, an experiment was designed to compare the effects of a high
      lactose and a high-fat MR on glucose homeostasis and insulin sensitivity in veal
      calves. Sixteen male Holstein-Friesian calves (120+/-2.8kg of BW) were assigned
      to either a high-lactose (HL) or a high-fat (HF) MR for 13 consecutive weeks.
      After at least 7 wk of adaptation, whole-body insulin sensitivity and insulin
      secretion were assessed by euglycemic-hyperinsulinemic and hyperglycemic clamps,
      respectively. Postprandial blood samples were collected to assess glucose,
      insulin, and triglyceride responses to feeding, and 24-h urine was collected to
      quantify urinary glucose excretion. At the end of the trial, liver and muscle
      biopsies were taken to assess triglyceride contents in these tissues. Long-term
      exposure of calves to HF or HL MR did not affect whole-body insulin sensitivity
      (averaging 4.2+/-0.5*10-2 [(mg/kg?min)/(MUU/mL)]) and insulin secretion.
      Responses to feeding were greater for plasma glucose and tended to be greater for
      plasma insulin in HL calves than in HF calves. Urinary glucose excretion was
      substantially higher in HL calves (75+/-13g/d) than in HF calves (21+/-6g/d).
      Muscle triglyceride content was not affected by treatment and averaged 4.5+/
      0.6g/kg, but liver triglyceride content was higher in HF calves (16.4+/-0.9g/kg)
      than in HL calves (11.2+/-0.7g/kg), indicating increased hepatic fat
      accumulation. We conclude that increasing the contribution of fat to the
      digestible energy intake from the MR from 20 to 50%, at the expense of lactose
      does not affect whole-body insulin sensitivity and insulin secretion in calves.
      However, a high-lactose MR increases postprandial glucose and insulin responses,
      whereas a high-fat MR increases fat accumulation in liver but not muscle.

PMID- 27720158
TI  - Mortality risk factors for calves entering a multi-location white veal farm in
      Ontario, Canada.
AB  - Mortality in preweaned dairy-breed calves, whether they are replacement dairy
      heifers, veal animals, or dairy beef animals, represents both a welfare issue and
      a source of economic loss for the industries involved. Studies describing
      morbidity and mortality in veal calves have illustrated different management
      practices and requirements in terms of housing and nutrition around the world.
      Studies examining the rearing of replacement dairy heifers have shown that rates
      of morbidity and mortality can vary dramatically between farms, perhaps
      reflecting differences in management strategies. It has been over 2 decades since
      morbidity and mortality in veal calves in Ontario were described. The objective
      of this retrospective population cohort study was to describe mortality and
      determine whether on-arrival information could be used to predict mortality risk.
      Predictors could be used to both better classify and group calves on arrival and
      provide feedback to suppliers about the characteristics of the highest- and
      lowest-risk calves. We collected data from 10,910 calves entering 7 barns of a
      single white veal farm, all in Ontario, from January 1 to December 31, 2014.
      Calves were followed until death or marketing (typically 140 to 150 d). We
      developed logistic regression models to determine the effects of weight on
      arrival, season of arrival, supplier, sex, barn, and purchase price on the risk
      of total mortality, early mortality (0-21d after arrival), and late mortality
      (>21d after arrival). We identified significant associations between season,
      barn, supplier, weight, and total mortality risk, with lighter-weight calves
      arriving in winter being at increased risk. Early mortality was significantly
      associated with weight, season, barn, and supplier, and tended to be associated
      with standardized price; lighter-weight calves arriving in winter at lower prices
      were at increased risk. Late mortality was significantly associated with season
      of arrival, barn, and supplier. On-arrival measures better predicted early
      mortality compared with late or total mortality. A further exploration of risk
      factors from the dairy farm of origin for veal calf mortality would serve to
      improve the productivity and welfare of calves of both sexes born on dairy farms.

PMID- 27720159
TI  - Evaluation of dietary betaine in lactating Holstein cows subjected to heat
      stress.
AB  - Betaine (BET), a natural, organic osmolyte, improves cellular efficiency by
      acting as a chaperone, refolding denatured proteins. To test if dietary BET
      reduced the effect of heat stress (HS) in lactating dairy cows, multiparous,
      lactating Holstein cows (n=24) were blocked by days in milk (101.4+/-8.6 d) and
      randomly assigned to 1 of 3 daily intakes of dietary BET: the control (CON) group
      received no BET, mid intake (MID) received 57mg of BET/kg of body weight, and
      high dose (HI) received 114mg of BET/kg of body weight. Cows were fed twice daily
      and BET was top-dressed at each feeding. Cows were milked 2 times/d and milk
      samples were taken daily for analysis. Milk components, yield, feed intake, and
      water intake records were taken daily. Rectal temperature and respiration rate
      were taken 3 times/d at 0600, 1400, and 1800h. Cows were housed in
      environmentally controlled rooms and were allowed acclimation for 7d at
      thermoneutral (TN) conditions with a mean temperature-humidity index of 56.6.
      Cows were then exposed to 7d of TN followed by 7d of HS represented by a
      temperature-humidity index of 71.5 for 14d. This was followed by a recovery
      period of 3d at TN. Dietary BET increased milk yield during the TN period. No
      differences were found between BET and CON in total milk production or milk
      composition during HS. The increase in water intake during HS was not as great
      for cows fed BET compared with controls. The cows on CON diets had higher p.m.
      respiration rate than both MID and HI BET during HS, but lower rectal temperature
      compared with BET. No difference was found in serum glucose during TN, but cows
      given HI had elevated glucose levels during HS compared with CON. No differences
      were found in serum insulin levels between CON and BET but an intake by
      environment interaction was present with insulin increasing in HI-treated
      lactating dairy cows during HS. The heat shock response [heat shock protein (HSP)
      27 and HSP70] was upregulated in bovine mammary epithelial cells in vitro. Blood
      leukocyte HSP27 was downregulated at the HI dose under TN conditions and HSP70
      was upregulated at the HI dose and this effect was increased by HS. No effect was
      seen with the MID dose with HSP27 or HSP70. The lack of effect of BET at MID may
      be associated with uptake across the gut. We conclude that BET increased milk
      production under TN conditions and was associated with reduced feed and water
      intake and slightly increased body temperatures during HS of cows fed BET. The
      effect of BET on milk production was lost during HS with HI BET, whereas serum
      glucose levels increased during HS.

PMID- 27720160
TI  - Identifying management and disease priorities of Canadian dairy industry
      stakeholders.
AB  - The objective of this study was to identify the key management and disease issues
      affecting the Canadian dairy industry. An online questionnaire (FluidSurveys,
      http://fluidsurveys.com/) was conducted between March 1 and May 31, 2014. A total
      of 1,025 responses were received from across Canada of which 68% (n=698) of
      respondents were dairy producers, and the remaining respondents represented
      veterinarians, university researchers, government personnel, and other allied
      industries. Participants were asked to identify their top 3 management and
      disease priorities from 2 lists offered. Topics were subsequently ranked from
      highest to lowest using 3 different ranking methods based on points: 5-3-1 (5
      points for first priority, 3 for second, and 1 for first), 3-2-1, and 1-1-1
      (equal ranking). The 5-3-1 point system was selected because it minimized the
      number of duplicate point scores. Stakeholder groups showed general agreement
      with the top management issue identified as animal welfare and the number one
      health concern as lameness. Other areas identified as priorities were
      reproductive health, antibiotic use, bovine viral diarrhea, and Staphylococcus
      aureus mastitis with these rankings influenced by region, herd size, and
      stakeholder group. This is the first national comprehensive assessment of
      priorities undertaken in the Canadian dairy industry and will assist researchers,
      policymakers, program developers, and funding agencies make future decisions
      based on direct industry feedback.

PMID- 27720161
TI  - Effect of pasture versus indoor feeding systems on raw milk composition and
      quality over an entire lactation.
AB  - The aim of this study was to investigate the effects of different feeding systems
      on milk quality and composition. Fifty-four multiparous and primiparous Friesian
      lactating cows were divided into 3 groups (n=18) to study the effects of 3
      feeding systems over a full lactation. Group 1 was housed indoors and offered a
      total mixed ration diet (TMR), group 2 was maintained outdoors on a perennial
      ryegrass pasture (referred to as grass), and group 3 was also grazed outdoors on
      a perennial ryegrass/white clover pasture (referred to as clover). Bulk milk
      samples were collected from each group at morning and afternoon milkings once
      weekly from March 11 to October 28 in 2015. Milk from pasture-fed cows (grass and
      clover) had significantly higher concentrations of fat, protein, true protein,
      and casein. The pasture feeding systems induced significantly higher
      concentrations of saturated fatty acids C11:0, C13:0, C15:0, C17:0, C23:0, and
      unsaturated fatty acids C18:2n-6 trans, C18:3n-3, C20:1, and C20:4n-6 and a
      greater than 2-fold increase in the conjugated linoleic acid C18:2 cis-9,trans-11
      content of milk compared with that of the TMR feeding system. The TMR feeding
      system resulted in milks with increased concentrations of C16:0, C18:2n-6 cis,
      C18:3n-6 cis, C22:0 C22:1n-9, and C18:2 cis-10,trans-12. Principal component
      analysis of average fatty acid profiles showed clear separation of milks from the
      grazed pasture-based diets to that of a TMR system throughout lactation, offering
      further insight into the ability to verify pasture-derived milk by fatty acid
      profiling.

PMID- 27720162
TI  - Is subclinical hypothyroidism associated with lower live birth rates in women who
      have experienced unexplained recurrent miscarriage?
AB  - Thyroid disorders have been associated with recurrent miscarriage. Little
      evidence is available on the influence of subclinical hypothyroidism on live
      birth rates. In this cohort study, women who had experienced miscarriage and
      subclinical hypothyroidism (defined as thyroid-stimulating hormone >97.5th
      percentile mU/l with a normal thyroxine level) were investigated; the control
      group included women who had experienced recurrent miscarriage and normal thyroid
      function. Multivariable logistic regression was used to investigate the
      association of subclinical hypothyroidism. Data were available for 848 women; 20
      (2.4%) had subclinical hypothyroidism; 818 women (96%) had euthyroidism; and 10
      (1.2%) had overt hypothyroidism. The live birth rate was 45% in women with
      subclinical hypothyroidism and 52% in euthyroid women (OR 0.69, 95% CI 0.28 to
      1.71). The ongoing pregnancy rate was 65% versus 69% (OR 0.82, 95% CI 0.32 to
      2.10) and the miscarriage rate was 35% versus 28% (OR 1.43, 95% CI 0.56 to 3.68),
      respectively. No differences were found when thyroid stimulating hormone 2.5 mU/l
      was used as cut-off level to define subclinical hypothyroidism. In women with
      unexplained miscarriage, no differences were found in live birth, ongoing
      pregnancy and miscarriage rates between women with subclinical hypothyroidism and
      euthyroid women.

PMID- 27720163
TI  - The effect of intravenous immunoglobulin passive immunotherapy on unexplained
      recurrent spontaneous abortion: a meta-analysis.
AB  - The aim of this study was to investigate the effect of passive immunotherapy
      using intravenous immunoglobulin (IVIG) on unexplained recurrent spontaneous
      abortion (RSA). Live birth rates were analysed and binary data were calculated
      using risk ratio and 95% confidence interval. Meta-analysis of 11 studies showed
      that the difference in the live birth rate between the IVIG treatment and placebo
      groups was on the margin of significance (RR = 1.25, 95% CI 1.00 to 1.56, P =
      0.05). Both cumulative and trial sequential meta-analyses indicated potential
      beneficial effect of IVIG but the evidence was inconclusive. Subgroup analysis
      showed that the live birth rate in primary (RR = 0.88, 95% CI 0.71 to 1.07) and
      secondary (RR = 1.26, 95% CI 0.99 to 1.61) RSA patients was not significantly
      different between the IVIG and placebo groups. Live birth rate was significantly
      different when IVIG was administered before conception (RR = 1.67, 95% CI 1.30 to
      2.14, P < 0.0001) but not after implantation (RR = 1.10, 95% CI 0.93 to 1.29).
      Evidence is insufficient to support the beneficial effects of IVIG on an
      unexplained RSA. Further high quality studies are needed to elucidate the
      effectiveness of IVIG.

PMID- 27720164
TI  - Survival of Patients With Advanced or Metastatic Renal Cell Carcinoma in Routine
      Practice Differs From That in Clinical Trials-Analyses From the German Clinical
      RCC Registry.
AB  - INTRODUCTION: Because "real-life" patients often do not meet the strict
      eligibility criteria of clinical trials, we assessed the trial eligibility of
      patients with advanced or metastatic renal cell carcinoma (mRCC) in routine
      practice and compared the survival of "trial-ineligible" and potentially "trial
      eligible" patients. PATIENTS AND METHODS: The present prospective, multicenter
      German cohort study is recruiting patients from 110 oncology/urology outpatient
      centers and hospitals at initiation of systemic first-line treatment. The
      demographic, clinical, treatment, and survival data were collected. We defined
      patients as "trial-ineligible" when >= 1 exclusion criterion (Karnofsky
      performance status < 80%, hemoglobin less than the lower limit of normal, non
      clear cell carcinoma histology) was documented. Otherwise, the patients were
      considered "trial-eligible". RESULTS: Of 732 patients included, 57% were
      classified as "trial-ineligible". Overall, the median first-line progression-free
      survival (PFS) was 7.9 months (95% confidence interval [CI], 6.9-8.9 months). The
      median first-line PFS of "trial-eligible" and "trial-ineligible" patients was
      11.0 months (95% CI, 9.6-13.1 months) and 5.3 months (95% CI, 4.6-6.5 months),
      respectively. The median OS of the "trial-eligible" and "trial-ineligible"
      patients was 26.0 months (95% CI, 22.1-29.7 months) and 12.6 months (95% CI, 10.6
      15.8 months), respectively. CONCLUSION: Our data suggest that patients in routine
      practice differ from patients treated in clinical trials and that almost 60% of
      mRCC patients in German routine practice would be ineligible for participation in
      clinical trials. While their first-line PFS and OS were shorter than those of
      "trial-eligible" patients, the PFS and OS of "trial-eligible" patients were
      comparable with the results from clinical trials. Physicians should be aware of
      these differences when discussing treatment options and outcome expectations with
      patients.

PMID- 27720165
TI  - Policy interventions related to medicines: Survey of measures taken in European
      countries during 2010-2015.
AB  - BACKGROUND: Policy-makers can use a menu of pharmaceutical policy options. This
      study aimed to survey these measures that were implemented in European countries
      between 2010 and 2015. METHODS: We did bi-annual surveys with competent
      authorities of the Pharmaceutical Pricing and Reimbursement Information network.
      Additionally, we consulted posters produced by members of this network as well as
      further published literature. Information on 32 European countries (all European
      Union Member States excluding Luxembourg; Iceland, Norway, Serbia, Switzerland,
      Turkey) was included. RESULTS: 557 measures were reported between January 2010
      and December 2015. The most frequently mentioned measure was price reductions and
      price freezes, followed by changes in patient co-payments, modifications related
      to the reimbursement lists and changes in distribution remuneration. Most policy
      measures were identified in Portugal, Greece, Belgium, France, the Czech
      Republic, Iceland, Spain and Germany. 22% of the measures surveyed could be
      classified as austerity. CONCLUSIONS: Countries that were strongly hit by the
      financial crisis implemented most policy changes, usually aiming to generate
      savings and briefly after the emergence of the crisis. Improvements in the
      economic situation tended to lead to an easing of austerity measures. Countries
      also implemented policies that aimed to enhance enforcement of existing measures
      and increase efficiency.

PMID- 27720166
TI  - Cardiac surgery in low-income settings: 10 years of experience from two
      countries.
AB  - BACKGROUND: Access to cardiac surgery is limited in low-income settings, and data
      on patient outcomes are scarce. AIMS: To assess characteristics, surgical
      procedures and outcomes in patients undergoing open-heart surgery in low-income
      settings. METHODS: This was a cohort study (2001-2011) in two low-income
      countries, Cambodia and Mozambique, where cardiac surgery had been promoted by
      visiting non-governmental organizations. RESULTS: In Cambodia and Mozambique,
      respectively, 1332 and 767 consecutive patients were included; 547 (41.16%) and
      385 (50.20%) were men; median age at first surgery was 11 years (interquartile
      range [IQR] 4-14) and 11 years (IQR 3-18); rheumatic heart disease affected 490
      (36.79%) and 268 (34.94%) patients; congenital heart disease (CHD) affected 834
      (62.61%) and 390 (50.85%) patients, with increasingly more CHD patients over time
      (P<0.001); and the number of patients lost to follow-up reached 741 (55.63%) and
      112 (14.6%) at 30 days. A total of 249 (32.46%) patients were lost to follow-up
      in Mozambique, remoteness being the only influencing factor (P<0.001). Among
      patients with known vital status, the early (<30 days) postoperative mortality
      rate was 6.10% (n=40) in Mozambique and 3.05% (n=18) in Cambodia. Overall, 109
      (8.18%) patients in Cambodia and 94 (12.26%) patients in Mozambique underwent re
      do surgery. In Mozambique, a further 50/518 (9.65%) patients died at a median of
      23months (IQR 7-43); in Cambodia, a further 34/591 (5.75%) patients died at a
      median of 11.5months (IQR 6-54.5). CONCLUSIONS: Cardiac surgery is feasible in
      low-income countries with acceptable in-hospital mortality and proof of capacity
      building. Patient outcomes after cardiac surgery in low-income countries remain
      unknown, given the strikingly high numbers of lost to follow-up.

PMID- 27720167
TI  - Coronary artery bypass grafting for left main disease and the risk of stroke:
      Incidence, aetiology and prevention.
AB  - This review explores the association between left main disease and the increased
      risk of perioperative stroke following coronary artery bypass grafting,
      specifically addressing the potential underlying mechanisms and its potential
      prevention. In particular, this correlation appears stronger for patients with
      left main disease when compared to patients with isolated triple vessel disease.
      Even though evidence on this topic is limited and of modest quality, there
      appears to be a significant association between ascending aorta atherosclerosis
      and coronary artery disease. Furthermore, there seems to be a relationship
      between the severity and extent of carotid artery stenosis and coronary artery
      disease. Carotid artery disease is itself associated with atherosclerosis of the
      ascending aorta, a well-recognised risk factor for postoperative atheroembolic
      stroke. The association between left main disease, ascending aorta
      atherosclerosis and carotid artery stenosis may reflect an increased systemic
      atherosclerotic burden and hence explain, at least partially, the higher risk of
      perioperative cerebrovascular events. Potential pre-, intra- and post-operative
      strategies for stroke prevention are discussed.

PMID- 27720168
TI  - Challenges for stem cell-based "regenerative prosthodontics".

PMID- 27720169
TI  - Drug-Induced Sleep Endoscopy.
AB  - Drug-induced sleep endoscopy (DISE) is an upper airway evaluation technique in
      which fiberoptic examination is performed under conditions of unconscious
      sedation. Unique information obtained from this 3-dimensional examination of the
      airway potentially provides additive benefits to other evaluation methods to
      guide treatment selection. This article presents recommendations regarding DISE
      technique and the VOTE Classification system for reporting DISE findings and
      reviews the evidence concerning DISE test characteristics and the association
      between DISE findings and treatment outcomes.

PMID- 27720170
TI  - A transcriptome resource for the deep-sea bacterium Shewanella piezotolerans WP3
      under cold and high hydrostatic pressure shock stress.
AB  - Low temperature and high hydrostatic pressure (HHP) are two of the most
      remarkable environmental factors influencing deep-sea ecosystem. The adaptive
      mechanisms of microorganisms which live in these extreme environments to low
      temperature and high pressure warrant investigation. In this study, the global
      gene expression patterns of the deep-sea bacterium Shewanella piezotolerans WP3
      in response to cold (0  degrees C) and HHP (50 MPa) shock were evaluated through
      DNA microarray analysis. Results revealed that 22, 66, and 106 genes were
      differentially expressed after WP3 was respectively exposed to cold shock for 30,
      60, and 90 min. Of these genes, 16 genes were identified as common differentially
      expressed genes (DEGs). After 30 min and 120 min of HHP shock, 5 and 10 genes
      were respectively identified as DEGs. The hierarchical clustering analysis of the
      DEG pattern indicated that WP3 may employ different adaptive strategies to cope
      with cold and HHP shock stress. Taken together, our study provided a
      transcriptome resource for deep-sea bacterial responses to cold and HHP stress.
      This study also established a basis for further investigations on environmental
      adaptive mechanisms utilized by benthic bacteria.

PMID- 27720171
TI  - Composite glycerol/graphite/aromatic acid matrices for thin-layer
      chromatography/matrix-assisted laser desorption/ionization mass spectrometry of
      heterocyclic compounds.
AB  - New composite matrices have been suggested for the analysis of mixtures of
      different synthetic organic compounds (N-containing heterocycles and erectile
      dysfunction drugs) by thin layer chromatography/matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (TLC/MALDI-TOF). Different mixtures
      of classical MALDI matrices and graphite particles dispersed in glycerol were
      used for the registration of MALDI mass spectra directly from TLC plates after
      analytes separation. In most of cases, the mass spectra possessed [M+H]+ ions;
      however, for some analytes only [M+Na]+ and [M+K]+ ions were observed. These ions
      have been used to generate visualized TLC chromatograms. The described approach
      increases the desorption/ionization efficiencies of analytes separated by TLC,
      prevent spot blurring, simplifies and decrease time for sample preparation.

PMID- 27720172
TI  - Nonlinear model predictive control applied to the separation of praziquantel in
      simulated moving bed chromatography.
AB  - An adaptive nonlinear model predictive control of a simulated moving bed unit for
      the enantioseparation of praziquantel is presented. A first principle model was
      applied at the proposed purity control scheme. The main concern about this kind
      of model in a control framework is in regard to the computational effort to solve
      it; however, a fast enough solution was achieved. In order to evaluate the
      controller's performance, several cases were simulated, including external pumps
      and switching valve malfunctions. The problem of plant-model mismatch was also
      investigated, and for that reason a parameter estimation step was introduced in
      the control strategy. In every studied scenario, the controller was able to
      maintain the purity levels at their set points, which were set to 99% and 98.6%
      for extract and raffinate, respectively. Additionally, fast responses and smooth
      actuation were achieved.

PMID- 27720173
TI  - Simulation and experimental study of enzyme and reactant mixing in capillary
      electrophoresis based on-line methods.
AB  - The establishment of an efficient reaction mixture represents a crucial part of
      capillary electrophoresis based on-line enzymatic assays. For ketamine N
      demethylation to norketamine mediated by the cytochrome P450 3A4 enzyme, mixing
      of enzyme and reactants in the incubation buffer at physiological pH was studied
      by computer simulation. A dynamic electrophoretic simulator that encompasses
      Taylor-Aris diffusivity which accounts for dispersion due to the parabolic flow
      profile associated with pressure driven flow was utilized. The simulator in the
      diffusion mode was used to predict transverse diffusional reactant mixing
      occurring during hydrodynamic plug injection of configurations featuring four and
      seven plugs. The same simulator in the electrophoretic mode was applied to study
      electrophoretic reactant mixing caused by voltage application in absence of
      buffer flow. Resulting conclusions were experimentally verified with
      enantioselective analysis of norketamine in a background electrolyte at low pH.
      Furthermore, simulations visualize buffer changes that occur upon power
      application between incubation buffer and background electrolyte and have an
      influence on the reaction mixture.

PMID- 27720174
TI  - Towards a chromatographic similarity index to establish localized quantitative
      structure-retention models for retention prediction: Use of retention factor
      ratio.
AB  - Quantitative Structure-Retention Relationships (QSRR) have the potential to speed
      up the screening phase of chromatographic method development as the initial
      exploratory experiments are replaced by prediction of analyte retention based
      solely on the structure of the molecule. The present study offers further proof
      of-concept of localized QSRR modelling, in which the retention of any given
      compound is predicted using only the most chromatographically similar compounds
      in the available dataset. To this end, each compound in the dataset was
      sequentially removed from the database and individually utilized as a test
      analyte. In this study, we propose the retention factor k as the most relevant
      chromatographic similarity measure and compare it with the Tanimoto index, the
      most popular similarity measure based on chemical structure. Prediction error was
      reduced by up to 8 fold when QSRR was based only on chromatographically similar
      compounds rather than using the entire dataset. The study therefore shows that
      the design of a practically useful structural similarity index should select the
      same compounds in the dataset as does the k-similarity filter in order to
      establish accurate predictive localized QSRR models. While low average prediction
      errors (Mean Absolute Error (MAE)<0.5min) and slopes of the regression lines
      through the origin close to 1.00 were obtained using k-similarity searching, the
      use of the structural Tanimoto similarity index, considered as the gold standard
      in Quantitative Structure-Activity Relationships (QSAR) studies, generally
      resulted in much higher prediction errors (MAE>1min) and significant deviations
      from the reference slope of 1.0. The Tanomoto similarity index therefore appears
      to have limited general utility in QSRR studies. Future studies therefore aim at
      designing a more appropriate chromatographic similarity index that can then be
      applied for unknown compounds (that is, compounds which have not been tested
      previously on the chromatographic system used, but for which the chemical
      structures are known).

PMID- 27720175
TI  - Determination of 3'-phosphoadenosine-5'-phosphosulfate in cells and Golgi
      fractions using hydrophilic interaction liquid chromatography-mass spectrometry.
AB  - 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) is a key player in the sulfation of
      biomolecules, but methods for selective measurements are lacking. A liquid
      chromatography-mass spectrometry (LC-MS) approach for measuring PAPS was
      developed. A central feature of the method was employing hydrophilic interaction
      liquid chromatography (HILIC), which is highly suited for separating very
      polar/charged compounds, and is compatible with electrospray MS. Using simple
      instrumentation, the analysis time per sample was below 10min and the method was
      characterized by easy sample preparation. The method was used to monitor
      decreasing levels of PAPS as function of sodium chlorate treatment (an inhibitor
      of PAPS synthesis) in whole-cell lysates as well as Golgi-fractions. The method
      allowed PAPS to be chromatographically separated from ADP and ATP, which can
      interfere with measurements if a less resolving LC-MS method is used.

PMID- 27720176
TI  - Presentations.

PMID- 27720177
TI  - Senescence of T Lymphocytes: Implications for Enhancing Human Immunity.
AB  - As humans live longer, a central concern is to find ways to maintain their health
      as they age. Immunity declines during ageing, as shown by the increased
      susceptibility to infection by both previously encountered and new pathogens and
      by the decreased efficacy of vaccination. It is therefore crucial to understand
      the mechanisms responsible for this decrease in immunity and to develop new
      strategies to enhance immune function in older humans. We discuss here how the
      induction of senescence alters leukocyte, and specifically T cell, function. An
      emerging concept is that senescence and nutrient sensing-signalling pathways
      within T cells converge to regulate functional responses, and the manipulation of
      these pathways may offer new ways to enhance immunity during ageing.

PMID- 27720179
TI  - Two new mutations of the CLMP gene identified in a newborn presenting congenital
      short-bowel syndrome.
AB  - Congenital short-bowel syndrome (CSBS) is a rare neonatal pathology associated
      with poor prognosis and high mortality rate. We describe a newborn presenting
      CSBS intestinal malrotation and chronic intestinal pseudo-obstruction syndrome
      (CIPS), compound heterozygous for two previously unreported heterozygous
      mutations in Coxsackie and adenovirus receptor-like membrane protein (CLMP) gene,
      one in intron 1 (c.28+1G>C), the other on exon 4 (c502C>T, p.R168X). Both
      mutations are predicted to be pathogenic, leading to impaired splicing and the
      appearance of a premature stop codon, respectively. Our case is remarkable in
      that it concerns two heterozygous truncating mutations associated with a good
      clinical prognosis with a favorable cerebral and gastrointestinal outcome and a
      substantial enteral input at 8 months of age, despite a small intestine measuring
      only 35cm.

PMID- 27720180
TI  - Feasibility of a low concentration test bolus in CT angiography.
AB  - AIM: To investigate the feasibility of using a low-concentration test bolus in
      abdominal aorta computed tomography (CT) angiography (CTA). MATERIALS AND
      METHODS: In 10 patients referred for CTA of the abdominal aorta with a body mass
      index (BMI) <=28 kg/m2, a standard test bolus of 10 ml contrast medium (CM; 350
      mg iodine/ml) was compared with a low-concentration test bolus (5 ml CM; 350 mg
      iodine/ml; 1:1 diluted with saline) in terms of time to peak enhancement (tPE)
      and peak enhancement (PE). RESULTS: No significant differences were found between
      the standard and low-concentration test bolus in terms of tPE and PE.
      CONCLUSIONS: A low-concentration test bolus (5 ml, 1:1 diluted with saline) is
      feasible in patients with a BMI <=28 kg/m2.

PMID- 27720178
TI  - Child-onset and adolescent-onset acquired thrombotic thrombocytopenic purpura
      with severe ADAMTS13 deficiency: a cohort study of the French national registry
      for thrombotic microangiopathy.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura is a rare thrombotic
      microangiopathy, related to a severe ADAMTS13 deficiency (a disintegrin and
      metalloprotease with thromboSpondin type 1 repeats, member 13; activity <10% of
      normal). Childhood-onset thrombotic thrombocytopenic purpura is very rare and
      initially often misdiagnosed, especially when ADAMTS13 deficiency is acquired
      (ie, not linked to inherited mutations of the ADAMTS13 gene). We aimed to
      investigate initial presentation, management, and outcome of acquired thrombotic
      thrombocytopenic purpura in children. METHODS: Between Jan 1, 2000, and Dec 31,
      2015, we studied a cohort of patients with child-onset and adolescent-onset
      acquired thrombotic thrombocytopenic purpura included in the French national
      registry for thrombotic microangiopathies at presentation and during follow up.
      The inclusion criteria were: first episode before age 18 years; ADAMTS13 activity
      less than 10% of normal at presentation; positive anti-ADAMTS13 autoantibodies
      during an episode, or a recovery of ADAMTS13 activity in remission, or both.
      ADAMTS13 activity and anti-ADAMTS13 autoantibodies were investigated by a central
      laboratory, and medical records were extensively reviewed to collect clinical and
      biological features with a standardised form. This study is registered with
      ClinicalTrials.gov, number NCT00426686. FINDINGS: We enrolled 973 patients with
      childhood-onset thrombotic microangiopathy, of whom 74 had a severe ADAMTS13
      deficiency (activity <10%) at presentation. 24 patients had an inherited
      thrombotic thrombocytopenic purpura also known as Upshaw-Schulman syndrome and
      five did not have follow-up data available, thus 45 children had acquired
      thrombotic thrombocytopenic purpura and were included in our database at
      presentation. 25 (56%) patients had idiopathic disease and 20 (44%) had
      miscellaneous associated clinical conditions. At diagnosis, median age was 13
      years (IQR 7-16, range 4 months-17 years), with a sex ratio of 2.5 girls to 1
      boy. Anti-ADAMTS13 autoantibodies were positive in 37 (82%) of 45 patients (24
      [96%] of 25 idiopathic cases and 13 [65%] of 20 non-idiopathic cases). 39 (87%)
      of 45 patients were given plasma therapy and 21 (47%) received additional
      rituximab. Four (9%) children died after the first thrombotic thrombocytopenic
      purpura episode. Long-term follow up of the 41 survivors showed that ten (24%)
      patients relapsed and systemic lupus erythematosus occurred in two (5%) patients.
      Preemptive rituximab was used in seven (17%) of 41 patients with acquired
      thrombotic thrombocytopenic purpura. INTERPRETATION: Our study shows that child
      onset and adolescent-onset acquired thrombotic thrombocytopenic purpura have
      specific clinical, biological and therapeutic features. Long-term follow-up is
      crucial to prevent relapses of the disease, to identify the occurrence of
      autoimmune disorders, and to evaluate consequences on social life. Child-onset
      and adolescent-onset acquired thrombotic thrombocytopenic purpura is a crucial
      diagnosis in the field of paediatric haematologic cytopenias because it is a life
      threatening disease requiring a specific management. FUNDING: Assistance Publique
      Hopitaux de Paris, France.

PMID- 27720181
TI  - Association between ventricular filling patterns and the extent of late
      enhancement on magnetic resonance imaging in patients with hypertrophic
      cardiomyopathy.
AB  - OBJECTIVE: To explore the relationship between ventricular filling curves and the
      extent of late enhancement on cardiac magnetic resonance imaging (MRI) in
      patients with hypertrophic cardiomyopathy. MATERIAL AND METHODS: We
      retrospectively included consecutive patients with suspected and/or confirmed
      hypertrophic cardiomyopathy and a control group of patients matched for age and
      sex who underwent cardiac MRI with evaluation of late enhancement. Among other
      determinations, we evaluated the following parameters on cine sequences: peak
      filling rate, time to the first peak filling rate, and filling rate normalized to
      the filling volume. RESULTS: Late enhancement was observed in 29 (73%) of the 40
      patients with hypertrophic cardiomyopathy. The normalized peak filling rate was
      significantly lower in patients with late enhancement (4.9 +/- 1.6 in those with
      hypertrophic cardiomyopathy positive for late enhancement vs. 5.8 +/- 2.2 in
      those with hypertrophic cardiomyopathy negative for late enhancement vs. 6.3 +/-
      1.5 in controls, p = 0.008) and the time to peak filling was longer in patients
      with late enhancement (540.6 +/- 89.7 ms vs. 505.5 +/- 99.3 ms in those with
      hypertrophic cardiomyopathy negative for late enhancement vs. 486.9 +/- 86.3 ms
      in controls, p = 0.02). When the population was stratified into three groups in
      function of the normalized peak filling rate, significant differences were
      observed among groups for age (p = 0.002), mean wall thickness (p = 0.036), and
      myocardial mass (p = 0.046) and atrial dimensions, whereas no significant
      differences with respect to late enhancement were seen. CONCLUSIONS: In patients
      with hypertrophic cardiomyopathy, we found a significant association between
      ventricular filling patterns and age, wall thicknesses, and atrial dimensions,
      but not with the extent of late enhancement.

PMID- 27720183
TI  - Corrigendum to "Adverse cardiac events in 56,000 orthopaedic trauma patients:
      Does anatomic area make a difference?" [Injury 47 (2016) 1856-1861].

PMID- 27720182
TI  - Plate fixation in periprosthetic femur fractures Vancouver type B1-Trochanteric
      hook plate or subtrochanterical bicortical locking?
AB  - INTRODUCTION: Proximal plate fixation in periprosthetic femur fractures can be
      improved by plate anchorage in the greater trochanter (lateral tension band
      principle) or bicortical locking screw placement beside the prosthesis stem in an
      embracement configuration. Both concepts were compared in a biomechanical test
      using a femoral hook plate (hook) or a locking attachment plate (LAP). METHODS:
      After bone mineral density (BMD) measurement in the greater trochanter, six pairs
      of fresh frozen human femora were assigned to two groups and instrumented with
      cemented hip endoprostheses. A transverse osteotomy was set distal to the tip of
      the prosthesis, simulating a Vancouver B1 fracture. Each pair was instrumented
      using a plate tensioner with either hook or LAP construct. Cyclic testing (2Hz)
      with physiologic profile and monotonically increasing load was performed until
      catastrophic failure. Plate stiffness was compared in a four-point-bending-test.
      Paired student's-t-test was used for statistical evaluation (p<0.05). RESULTS:
      Mean BMD was 250mgHA/ccm+/-47. The hook construct exhibited a significantly
      (p=0.015) lower number of cycles and load to failure (26'177cycles+/-2777;
      3'118N+/-778) correlating significantly with BMD (R2=0.83; p=0.04) compared to
      the LAP construct (37'423cycles+/-5'299; 4'242N+/-1'030) (R2=0.71;p=0.11). BMD
      was a significant covariate (p=0.01). Plate stiffness was in a comparable range
      (hook Plate 468N/mm+/-7; LCP 445N/mm+/-6). CONCLUSION: Subtrochanterically placed
      LAP provides an increased fixation strength under repetitive loading compared to
      hook plate fixation in the greater trochanter. Trochanteric fixation is highly
      BMD dependent and may be restricted to major greater trochanteric involvement
      requiring stabilization.

PMID- 27720185
TI  - Herniated liver mimicking an intracardiac mass in a newborn with omphalocele.

PMID- 27720186
TI  - Role of Soft-Tissue Heterogeneity in Computational Models of Deep Brain
      Stimulation.
AB  - BACKGROUND: Bioelectric field models of deep brain stimulation (DBS) are commonly
      utilized in research and industrial applications. However, the wide range of
      different representations used for the human head in these models may be
      responsible for substantial variance in the stimulation predictions. OBJECTIVE:
      Determine the relative error of ignoring cerebral vasculature and soft-tissue
      heterogeneity outside of the brain in computational models of DBS. METHODS: We
      used a detailed atlas of the human head, coupled to magnetic resonance imaging
      data, to construct a range of subthalamic DBS volume conductor models. We
      incrementally simplified the most detailed base model and quantified changes in
      the stimulation thresholds for direct activation of corticofugal axons. RESULTS:
      Ignoring cerebral vasculature altered predictions of stimulation thresholds by
      <10%, whereas ignoring soft-tissue heterogeneity outside of the brain altered
      predictions between -44 % and 174%. CONCLUSIONS: Heterogeneity in the soft
      tissues of the head, if unaccounted for, introduces a degree of uncertainty in
      predicting electrical stimulation of neural elements that is not negligible and
      thereby warrants consideration in future modeling studies.

PMID- 27720187
TI  - Elements of cultural competence in an Australian Aboriginal maternity program.
AB  - BACKGROUND: Pregnancy, labour and neonatal health outcomes for Australian
      Aboriginal women and their infants are frequently worse than those of the general
      population. Provision of culturally competent services may reduce these
      differences by improving access to timely and regular antenatal care. In an
      effort to address these issues, the Aboriginal Maternity Group Practice Program
      commenced in south metropolitan Perth, Western Australia, in 2011. The program
      employed Aboriginal Grandmothers, Aboriginal Health Officers and midwives working
      in a partnership model with pre-existing maternity services in the area. AIM: To
      identify elements of the Aboriginal Maternity Group Practice Program that
      contributed to the provision of a culturally competent service. METHODS: The
      Organisational Cultural Competence Assessment Tool was used to analyse
      qualitative data obtained from surveys of 16 program clients and 22 individuals
      from partner organisations, and interviews with 15 staff. FINDINGS: The study
      found that the partnership model positively impacted on the level of culturally
      appropriate care provided by other health service staff, particularly in
      hospitals. Two-way learning was a feature. Providing transport, team home visits
      and employing Aboriginal staff improved access to care. Grandmothers successfully
      brought young pregnant women into the program through their community networks,
      and were able to positively influence healthy lifestyle behaviours for clients.
      CONCLUSION: Many elements of the Aboriginal Maternity Group Practice Program
      contributed to the provision of a culturally competent service. These features
      could be considered for inclusion in antenatal care models under development in
      other regions with culturally diverse populations.

PMID- 27720184
TI  - Geriatric assault victims treated at U.S. trauma centers: Five-year analysis of
      the national trauma data bank.
AB  - INTRODUCTION: While geriatric trauma patients have begun to receive increased
      attention, little research has investigated assault-related injuries among older
      adults. Our goal was to describe characteristics, treatment, and outcomes of
      geriatric assault victims and compare them both to geriatric victims of
      accidental injury and younger assault victims. PATIENTS AND METHODS: We conducted
      a retrospective analysis of the 2008-2012 National Trauma Data Bank. We
      identified cases of assault-related injury admitted to trauma centers in patients
      aged >=60 using the variable "intent of injury." RESULTS: 3564 victims of assault
      related injury in patients aged >=60 were identified and compared to 200,194
      geriatric accident victims and 94,511 assault victims aged 18-59. Geriatric
      assault victims were more likely than geriatric accidental injury victims to be
      male (81% vs. 47%) and were younger than accidental injury victims (67+/-7 vs.
      74+/-9 years). More geriatric assault victims tested positive for alcohol or
      drugs than geriatric accident victims (30% vs. 9%). Injuries for geriatric
      assault victims were more commonly on the face (30%) and head (27%) than for
      either comparison group. Traumatic brain injury (34%) and penetrating injury
      (32%) occurred commonly. The median injury severity score (ISS) for geriatric
      assault victims was 9, with 34% having severe trauma (ISS>=16). Median length of
      stay was 3 days, 39% required ICU care, and in-hospital mortality was 8%. Injury
      severity was greater in geriatric than younger adult assault victims, and, even
      when controlling for injury severity, in-hospital mortality, length of
      hospitalization, and need for ICU-level care were significantly higher in older
      adults. CONCLUSIONS: Geriatric assault victims have characteristics and injury
      patterns that differ significantly from geriatric accidental injury victims.
      These victims also have more severe injuries, higher mortality, and poorer
      outcomes than younger victims. Additional research is necessary to improve
      identification of these victims and inform treatment strategies for this unique
      population.

PMID- 27720188
TI  - Usefulness of High-Frequency Ultrasound in the Classification of Histologic
      Subtypes of Primary Basal Cell Carcinoma.
AB  - INTRODUCTION: Incisional biopsy may not always provide a correct classification
      of histologic subtypes of basal cell carcinoma (BCC). High-frequency ultrasound
      (HFUS) imaging of the skin is useful for the diagnosis and management of this
      tumor. OBJECTIVES: The main aim of this study was to compare the diagnostic value
      of HFUS compared with punch biopsy for the correct classification of histologic
      subtypes of primary BCC. We also analyzed the influence of tumor size and
      histologic subtype (single subtype vs. mixed) on the diagnostic yield of HFUS and
      punch biopsy. METHODS: Retrospective observational study of primary BCCs treated
      by the Dermatology Department of Hospital Costa del Sol in Marbella, Spain,
      between october 2013 and may 2014. Surgical excision was preceded by HFUS imaging
      (Dermascan C(c), 20-MHz linear probe) and a punch biopsy in all cases. We
      compared the overall diagnostic yield and accuracy (sensitivity, specificity,
      positive predictive value [PPV], and negative predictive value [NPV]) of HFUS and
      punch biopsy against the gold standard (excisional biopsy with serial sections)
      for overall and subgroup results. RESULTS: We studied 156 cases. The overall
      diagnostic yield was 73.7% for HFUS (sensitivity, 74.5%; specificity, 73%) and
      79.9% for punch biopsy (sensitivity, 76%; specificity, 82%). In the subgroup
      analyses, HFUS had a PPV of 93.3% for superficial BCC (vs. 92% for punch biopsy).
      In the analysis by tumor size, HFUS achieved an overall diagnostic yield of 70.4%
      for tumors measuring 40mm2 or less and 77.3% for larger tumors; the NPV was 82%
      in both size groups. Punch biopsy performed better in the diagnosis of small
      lesions (overall diagnostic yield of 86.4% for lesions <=40mm2 vs. 72.6% for
      lesions >40mm2). CONCLUSIONS: HFUS imaging was particularly useful for ruling out
      infiltrating BCCs, diagnosing simple, superficial BCCs, and correctly classifying
      BCCs larger than 40mm2.

PMID- 27720189
TI  - [Purulent pericarditis in a patient with diabetes mellitus treated by
      percutaneous pericardiocentesis].
AB  - Purulent pericarditis seldom occurs in Western countries, yet its mortality rate
      remains high between 20 and 35 % despite early treatment. We report the case of a
      43-year-old patient admitted in the intensive cardiologic care unit with a pre
      tamponade, requiring an immediate percutaneous pericardiocentesis allowing the
      drainage of a purulent effusion. Evolution with antibiotic therapy adapted
      according to the bacteriological findings was favorable and 3-months follow-up
      shows a near complete regression of the effusion. This case recalls us this rare
      diagnosis entity and illustrates the possibility of a mere percutaneous
      pericardial drainage with the condition of a strict medical surveillance.

PMID- 27720191
TI  - Development of an intelligent surgical instrument for otitis media with effusion.
AB  - To treat a worldwide common ear disease (OME), a device allowing fast grommet
      tube insertion has been designed in our earlier works (Gao et al., 2015 [1] and
      Liang et al., 2013 [2]). However, the instrument has to be manually placed as
      close as to the Tympanic Membrane before the insertion procedures. To realize a
      fully automated surgical process, the instrument shall be automatically
      manipulated to align to the axial direction of ear canal and proceed to complete
      the surgery. A vision-based servomechanism is proposed to solve the path planning
      problem. A fuzzy-gain-scheduled controller is proposed to minimize the projection
      error based on the image detection and the proximity measurement. The proposed
      controller is proven to outperform the traditional PI controller in pre-clinical
      trials.

PMID- 27720192
TI  - Is anterior glenoid bone block position reliably assessed by standard
      radiography? A cadaver study.
AB  - BACKGROUND: Standard radiography with an antero-posterior view and Bernageau's
      glenoid profile view is the method most widely reported in the literature to
      assess coracoid bone block position and fusion. OBJECTIVE: The aim of this
      cadaver study was to determine whether the antero-posterior and Bernageau's
      radiographs provide a reliable and reproducible evaluation of the position of a
      coracoid bone block and its fixation screws. METHOD: An isolated scapula showing
      no evidence of osteoarthritis or other abnormalities was used. The coracoid
      process was transferred to the anterior glenoid rim. Fixation was with two
      slightly diverging malleolar screws, chosen of different sizes for ease of
      identification. Computed tomography (CT) was performed as the reference imaging
      technique. The standard radiographs were then obtained, using fluoroscopy to
      accurately position the scapula for the antero-posterior and Bernageau's views.
      This position was defined as 0 degrees , and radiographs were taken at angles of
      5 degrees , 10 degrees , and 15 degrees  in all three planes. All radiographs
      were taken during a single session to ensure that the distance separating the
      tube from the scapula remained unchanged. The images were exported to OsiriX for
      analysis. We measured the angles formed by the screws and the glenoid surface, as
      well as bone block position and overhang. Finally, we used 1-mm thick disks to
      evaluate bone-to-bone contact. RESULTS: No correlations were found between values
      by CT and by standard radiography (both views) for the screw angles or overhang.
      A space<=1mm between the neck of the scapula and the bone block was not visible
      on the standard radiographs in any of the positions. CONCLUSION: Standard
      radiography does not provide an accurate analysis of bone block position or bone
      to-bone contact. CT is needed to assess bone block and screw position and bone-to
      bone contact. LEVEL OF EVIDENCE: Level III.

PMID- 27720190
TI  - Past Roadblocks and New Opportunities in Transcription Factor Network Mapping.
AB  - One of the principal mechanisms by which cells differentiate and respond to
      changes in external signals or conditions is by changing the activity levels of
      transcription factors (TFs). This changes the transcription rates of target genes
      via the cell's TF network, which ultimately contributes to reconfiguring cellular
      state. Since microarrays provided our first window into global cellular state,
      computational biologists have eagerly attacked the problem of mapping TF
      networks, a key part of the cell's control circuitry. In retrospect, however,
      steady-state mRNA abundance levels were a poor substitute for TF activity levels
      and gene transcription rates. Likewise, mapping TF binding through chromatin
      immunoprecipitation proved less predictive of functional regulation and less
      amenable to systematic elucidation of complete networks than originally hoped.
      This review explains these roadblocks and the current, unprecedented blossoming
      of new experimental techniques built on second-generation sequencing, which hold
      out the promise of rapid progress in TF network mapping.

PMID- 27720193
TI  - Peri-articular local infiltration analgesia versus femoral nerve block for
      postoperative pain control following anterior cruciate ligament reconstruction:
      Prospective, comparative, non-inferiority study.
AB  - INTRODUCTION: Femoral nerve block (FNB) is considered as a major advance in
      anterior cruciate ligament (ACL) reconstruction as it reduces the need for
      parenteral opioids. However, the incidence of transient or even permanent
      neurological deficits due to the FNB is estimated at 1.94% after knee surgery.
      The primary objective of this study was to compare local infiltration analgesia
      (LIA) to FNB during ACL reconstruction procedures. The study hypothesis was that
      LIA was not less effective than FNB on early postoperative pain. PATIENTS AND
      METHODS: A retrospective analysis of data collected prospectively in the FAST
      cohort included a series of continuous patients who underwent primary repair for
      isolated ACL with a hamstring graft in 2013-2014. Changes in our anesthesia
      practices over time allowed us to form three successive groups: Group 1 - FNB,
      Group 2 - FNB+LIA, Group 3 - LIA only. Ultrasound-guided FNB was done pre
      operatively. The LIA was done at the end of the procedure by the surgeon with
      systematic infiltration of all skin incisions and the hamstring donor site; no
      intra-articular injections were performed. The primary endpoint was the average
      early postoperative pain (Days 0-3) described by the patient on a visual analogue
      scale (0-10). Sample size calculation pointed to 36 subjects being needed per
      group for a non-inferiority study. RESULTS: The study involved 126 patients:
      G1=42, G2=38, G3=46. The patients were comparable at enrolment. The average early
      postoperative pain levels were 3.1+/-2.4, 2.8+/-2.0 and 2.5+/-2.2, respectively
      (P=0.66). A trend toward higher intake of tramadol was noted in the LIA group on
      D0 to D3, with a significant trend test on Day 1 (P=0.03) and Day 2 (P=0.02).
      CONCLUSION: After reconstruction of isolated ACL tears with a hamstring graft,
      FNB is not more effective than LIA on patients' early postoperative pain.
      Patients who received a FNB consumed significantly less opioid-like analgesics.
      LEVEL OF EVIDENCE: III - Prospective, comparative, non-randomized study.

PMID- 27720194
TI  - Paired editorial: Inadequate protein intake following laparoscopic sleeve
      gastrectomy surgery is associated with a greater fat free mass loss.

PMID- 27720195
TI  - Can low BMI Chinese patients with type 2 diabetes benefit from laparoscopic Roux
      en-Y gastric bypass surgery?
AB  - BACKGROUND: The efficacy of laparoscopic Roux-en-Y gastric bypass (LRYGB) in type
      2 diabetes mellitus (T2D) is closely associated with the preoperative body mass
      index (BMI) of the patient. There is a lack of long-term and large sampling
      evidence on the efficacy of LRYGB in T2D patients with low BMI in China.
      OBJECTIVES: This retrospective study aimed to evaluate the efficacy of surgical
      treatment in a Chinese population with T2D (especially patients with BMI<27.5
      kg/m2). SETTING: University-affiliated hospital, China METHODS: Seventy-eight
      patients with T2D were included in the study and evaluated before and after LRYGB
      surgery. No patients were lost to follow-up at any time points. RESULTS: Thirty
      eight T2D patients with BMI>=27.5 kg/m2 in group 1 (high BMI group) had
      significant improvements in waist circumference, blood glucose levels,
      homeostasis model assessment-insulin resistance index, and C-peptide levels after
      LRYGB (P<.05). Forty T2D patients with BMI<27.5 kg/m2 in group 2 (low BMI group,
      including 19 T2D patients with BMI<25 kg/m2) had significant improvements in
      waist circumference and waist-to-hip ratio after LRYGB (P< .05). CONCLUSIONS:
      LRYGB surgery may be beneficial in T2D patients with BMI<27.5 kg/m2 in China.

PMID- 27720197
TI  - Long-term and midterm outcomes of laparoscopic sleeve gastrectomy versus Roux-en
      Y gastric bypass: a systematic review and meta-analysis of comparative studies.
AB  - OBJECTIVE: This study aimed to compare midterm and long-term weight loss and
      resolution of co-morbidity with laparoscopic Roux-en-Y gastric bypass (LRYGB) and
      laparoscopic sleeve gastrectomy (LSG). SUMMARY: LRYGB and LSG are the most common
      procedures performed in bariatric surgery. However, their weight loss efficacy in
      the midterm and long-term has not been well compared. METHODS: A meta-analysis
      was performed by systematically identifying comparative studies conducted until
      the end of June 2016 that investigated weight loss outcome and resolution of co
      morbidities (type 2 diabetes mellitus, hypertension, hyperlipidemia,
      hypertriglyceridemia, and obstructive sleep apnea) with LRYGB and LSG in the
      midterm (3-5 years) and long term (>=5 years). The primary endpoint was weight
      loss after LRYGB versus LSG. The secondary endpoint was resolution of co
      morbidities after these procedures. RESULTS: Fourteen studies comprising 5264
      patients were eligible. Follow-up ranged from 36 months to 75.8+/-8.4 months. The
      pooled result for weight loss outcomes did not show any significant difference in
      midterm weight loss (standardized mean difference = -0.03; 95% confidence
      interval (CI), -0.38-.33; P = .88) but a significant difference in the long-term
      weight loss outcome favoring LRYGB (standardized mean difference = .17; 95% CI,
      .05-.28; P= .005). The pooled results demonstrated no significant difference for
      resolution of type 2 diabetes mellitus, hypertension, hyperlipidemia, and
      hypertriglyceridemia. CONCLUSION: Despite the insignificant difference between
      LRYGB and LSG in midterm weight loss, LRYGB produced better weight loss in the
      long-term. There was no significant difference between the 2 procedures for co
      morbidity resolution.

PMID- 27720196
TI  - Early improvement in obstructive sleep apnea and increase in orexin levels after
      bariatric surgery in adolescents and young adults.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) associated with obesity is known to
      improve after bariatric surgery, but little is known about early changes in this
      condition after surgery. OBJECTIVES: To study the clinical course of OSA after
      bariatric surgery SETTING: Children's hospital in the United States METHODS:
      Adolescents and young adults with obstructive sleep apnea undergoing vertical
      sleeve gastrectomy (n = 6) or gastric bypass (n = 1) were enrolled in this
      prospective study. Participants underwent formal polysomnography before and at 3
      and 5 weeks after bariatric surgery. Anthropometric measurements and assay for
      orexin and leptin were also performed at study visits. Thirty-one adolescents who
      underwent 2 polysomnography studies that were 4 weeks apart served as control
      patients. RESULTS: Baseline mean (range) age of participants was 17.8 (15.4-20.7)
      years, 71% were male, with body mass index of 55.2 (41.3-61.6) kg/m2 and had a
      median apnea hypopnea index (AHI) of 15.8 (7.1-23.8) events/hour. Differences in
      least-square means from longitudinal analysis did not show significant
      differences in AHI in the control group but showed significant postoperative
      decline in AHI relative to baseline. AHI declined postoperatively from baseline
      by 9.2 events/hour (95% confidence interval: 3.8 to 14.5) at 3 weeks (P = .002)
      and 9.1 events/hour (95% confidence interval: 3.8 to 14.5) at 5 weeks (P = .002);
      there was no significant change from 3 to 5 weeks in AHI. Leptin decreased and
      orexin levels increased significantly by 3 weeks postoperatively. CONCLUSIONS:
      These observations suggest that OSA responds early and out of proportion to
      weight loss after metabolic and or bariatric surgery, thus weight independent
      factors may at least in part be responsible for early improvement in OSA
      postoperatively.

PMID- 27720199
TI  - Connectome Disconnectivity and Cortical Gene Expression in Patients With
      Schizophrenia.
AB  - BACKGROUND: Genome-wide association studies have identified several common risk
      loci for schizophrenia (SCZ). In parallel, neuroimaging studies have shown
      consistent findings of widespread white matter disconnectivity in patients with
      SCZ. METHODS: We examined the role of genes in brain connectivity in patients
      with SCZ by combining transcriptional profiles of 43 SCZ risk genes identified by
      the recent genome-wide association study of the Schizophrenia Working Group of
      the Psychiatric Genomics Consortium with data on macroscale connectivity
      reductions in patients with SCZ. Expression profiles of 43 Psychiatric Genomics
      Consortium SCZ risk genes were extracted from the Allen Human Brain Atlas, and
      their average profile across the cortex was correlated to the pattern of cortical
      disconnectivity as derived from diffusion-weighted magnetic resonance imaging
      data of patients with SCZ (n = 48) and matched healthy controls (n = 43).
      RESULTS: The expression profile of SCZ risk genes across cortical regions was
      significantly correlated with the regional macroscale disconnectivity (r = .588;
      p = .017). In addition, effects were found to be potentially specific to SCZ,
      with transcriptional profiles not related to cortical disconnectivity in patients
      with bipolar I disorder (diffusion-weighted magnetic resonance imaging data; 216
      patients, 144 controls). Further examination of correlations across all 20,737
      genes present in the Allen Human Brain Atlas showed the set of top 100 strongest
      correlating genes to display significant enrichment for the disorder, potentially
      identifying new genes involved in the pathophysiology of SCZ. CONCLUSIONS: Our
      results suggest that under disease conditions, cortical areas with pronounced
      expression of risk genes implicated in SCZ form central areas for white matter
      disconnectivity.

PMID- 27720200
TI  - Facial Nerve Schwannomas: Review of 80 Cases Over 25 Years at Mayo Clinic.
AB  - OBJECTIVE: To elucidate the long-term clinical behavior, treatment, and outcomes
      of sporadic facial nerve schwannoma (FNS) in a large cohort of patients managed
      in the post-magnetic resonance imaging era. PATIENTS AND METHODS: Retrospective
      review at a single tertiary health care system (January 1, 1990, through December
      31, 2015), evaluating 80 consecutive patients with sporadic FNS. RESULTS: Ninety
      eight patients with FNS were identified; 10 with incomplete data and 8 with
      neurofibromatosis type 2 were excluded. The remaining 80 patients (median age, 47
      years; 58% women) were analyzed. Forty-three (54%) patients presented with
      asymmetrical hearing loss, 33 (41%) reported facial paresis, and 21 (26%)
      reported facial spasm. Seventeen (21%) exhibited radiologic features mimicking
      vestibular schwannoma, 14 (18%) presented as a parotid mass, and 5 (6%) were
      discovered incidentally. Factors predictive of facial nerve paresis or spasm
      before treatment were female sex and tumor involvement of the
      labyrinthine/geniculate and tympanic facial nerve segments. The median growth
      rate among growing FNS was 2.0 mm/y. Details regarding clinical outcome according
      to treatment modality are described. CONCLUSION: In patients with FNS, female sex
      and involvement of the labyrinthine/geniculate and tympanic segments of the
      facial nerve predict a higher probability of facial paresis or spasm. When
      isolated to the posterior fossa or parotid gland, establishing a preoperative
      diagnosis of FNS is challenging. Treatment should be tailored according to tumor
      location and size, existing facial nerve function, patient priorities, and age. A
      management algorithm is presented, prioritizing long-term facial nerve function.

PMID- 27720198
TI  - The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia.
AB  - The dopamine hypothesis is the longest standing pathoetiologic theory of
      schizophrenia. Because it was initially based on indirect evidence and findings
      in patients with established schizophrenia, it was unclear what role dopamine
      played in the onset of the disorder. However, recent studies in people at risk of
      schizophrenia have found elevated striatal dopamine synthesis capacity and
      increased dopamine release to stress. Furthermore, striatal dopamine changes have
      been linked to altered cortical function during cognitive tasks, in line with
      preclinical evidence that a circuit involving cortical projections to the
      striatum and midbrain may underlie the striatal dopamine changes. Other studies
      have shown that a number of environmental risk factors for schizophrenia, such as
      social isolation and childhood trauma, also affect presynaptic dopaminergic
      function. Advances in preclinical work and genetics have begun to unravel the
      molecular architecture linking dopamine, psychosis, and psychosocial stress.
      Included among the many genes associated with risk of schizophrenia are the gene
      encoding the dopamine D2 receptor and those involved in the upstream regulation
      of dopaminergic synthesis, through glutamatergic and gamma-aminobutyric acidergic
      pathways. A number of these pathways are also linked to the stress response. We
      review these new lines of evidence and present a model of how genes and
      environmental factors may sensitize the dopamine system so that it is vulnerable
      to acute stress, leading to progressive dysregulation and the onset of psychosis.
      Finally, we consider the implications for rational drug development, in
      particular regionally selective dopaminergic modulation, and the potential of
      genetic factors to stratify patients.

PMID- 27720201
TI  - Undersized Mitral Annuloplasty Increases Strain in the Proximal Lateral Left
      Ventricular Wall.
AB  - BACKGROUND: Recurrence of mitral regurgitation (MR) after undersized mitral
      annuloplasty (MA) for ischemic MR is as high as 60%, with the recurrence rate
      likely due to continued dilation of the left ventricle (LV). To better understand
      the causes of recurrent MR, we studied the effect of undersized MA on strain in
      the LV wall. We hypothesize that the acute change in ventricular shape induced by
      MA will cause increased strain in regions nearest the mitral valve. METHODS:
      Finite element models were previously reported, based on cardiac magnetic
      resonance images of 5 sheep with mild to moderate ischemic MR. A 24-mm saddle
      shaped rigid annuloplasty ring was modeled and used to simulate virtual MA.
      Longitudinal and myofiber strains were calculated at end-diastole and end
      systole, with preoperative early diastolic geometry as the reference state.
      RESULTS: The undersized MA significantly increased longitudinal strain at end
      diastole in the lateral LV wall. The effect was greatest in the proximal-lateral
      endocardial surface, where longitudinal strain after MA was approximately triple
      the preoperative strain (11.17% +/- 2.15% vs 3.45% +/- 0.92%, p = 0.0057). In
      contrast, postoperative end-diastolic fiber strain decreased in this same region
      (2.53% +/- 2.14% vs 7.72% +/- 1.79%, p = 0.0060). There were no significant
      changes in either strain type at end-systole. CONCLUSIONS: Undersized MA
      increased longitudinal strain in the proximal lateral LV wall at end-diastole.
      This procedure-related strain at the proximal-lateral LV wall may foster
      continued LV enlargement and subsequent recurrence of mitral regurgitation.

PMID- 27720202
TI  - Time-driven activity-based costing of low-dose-rate and high-dose-rate
      brachytherapy for low-risk prostate cancer.
AB  - PURPOSE: Cost estimates through traditional hospital accounting systems are often
      arbitrary and ambiguous. We used time-driven activity-based costing (TDABC) to
      determine the true cost of low-dose-rate (LDR) and high-dose-rate (HDR)
      brachytherapy for prostate cancer and demonstrate opportunities for cost
      containment at an academic referral center. METHODS AND MATERIALS: We implemented
      TDABC for patients treated with I-125, preplanned LDR and computed tomography
      based HDR brachytherapy with two implants from initial consultation through 12
      month followup. We constructed detailed process maps for provision of both HDR
      and LDR. Personnel, space, equipment, and material costs of each step were
      identified and used to derive capacity cost rates, defined as price per minute.
      Each capacity cost rate was then multiplied by the relevant process time and
      products were summed to determine total cost of care. RESULTS: The calculated
      cost to deliver HDR was greater than LDR by $2,668.86 ($9,538 vs. $6,869). The
      first and second HDR treatment day cost $3,999.67 and $3,955.67, whereas LDR was
      delivered on one treatment day and cost $3,887.55. The greatest overall cost
      driver for both LDR and HDR was personnel at 65.6% ($4,506.82) and 67.0%
      ($6,387.27) of the total cost. After personnel costs, disposable materials
      contributed the second most for LDR ($1,920.66, 28.0%) and for HDR ($2,295.94,
      24.0%). CONCLUSIONS: With TDABC, the true costs to deliver LDR and HDR from the
      health system perspective were derived. Analysis by physicians and hospital
      administrators regarding the cost of care afforded redesign opportunities
      including delivering HDR as one implant. Our work underscores the need to assess
      clinical outcomes to understand the true difference in value between these
      modalities.

PMID- 27720203
TI  - Interstitial brachytherapy as a boost to patients with anal carcinoma and poor
      response to chemoradiation: Single-institution long-term results.
AB  - PURPOSE: To analyze the efficacy of a protocol-based brachytherapy (BT) boost
      after external beam radiation therapy (EBRT) with simultaneous chemotherapy in
      patients with anal carcinoma. METHODS AND MATERIALS: About 190 patients have been
      analyzed. Around 143 patients were identified with a good clinical response at
      the end of EBRT. Another 47 patients received an additional BT boost to the
      residual tumor at 6 weeks after end of chemoradiation. RESULTS: The 5-year
      incidence of local recurrence was 24% in patients with BT boost and 19% in
      patients without BT boost (p = 0.238). The 5-year disease-free survival rate,
      overall survival rate, and colostomy-free survival rate were 64% and 75% and
      76.1% in the BT group and 69% (p = 0.212), 72% (p = 0.924), and 82.7% (p = 0.488)
      in the non-BT group. We found no differences in late toxicity between the groups.
      CONCLUSIONS: For patients with anal cancer with not a good response to 50-59 Gy
      EBRT with simultaneous chemotherapy, the further dose escalation using the BT
      boost up to a mean of 67.5 Gy seems to improve the clinical outcome to the same
      level as observed in patients with a good response to ERBT, without an increase
      in late side effects.

PMID- 27720204
TI  - Brachytherapy should not be omitted when treating locally advanced neuroendocrine
      cervical cancer with definitive chemoradiation therapy.
AB  - PURPOSE: Neuroendocrine cervical cancer is a rare malignancy with a poor
      prognosis, yet there is a paucity of data to guide treatment decisions when
      managing patients with this diagnosis. Specifically, there are little data to aid
      practitioners in deciding if there is added value to brachytherapy given the
      additional time, cost, discomfort, and toxicity to patients. METHODS AND
      MATERIALS: We used the National Cancer Data Base to identify women with locally
      advanced neuroendocrine cervical cancer treated with definitive chemoradiotherapy
      to determine if the addition of brachytherapy improves outcomes in this disease.
      We also assessed outcomes based on chemotherapy timing in this cohort. RESULTS:
      We identified 100 patients with locally advanced nonmetastatic neuroendocrine
      cervical cancer that were treated with definitive chemoradiotherapy between 2004
      and 2012. There was a substantial improvement in overall survival when
      brachytherapy was administered in addition to external beam radiotherapy. In
      multivariate analysis, the addition of brachytherapy, compared with external beam
      radiotherapy alone, was associated with an improved median survival of 48.6 vs.
      21.6 months (hazard ratio (HR), 0.475; 95% CI, 0.255-0.883; p = 0.019). We
      observed no difference in overall survival for patients treated with neoadjuvant
      chemotherapy compared with the group who received chemotherapy started
      concurrently with radiation (HR, 0.851; 95% CI, 0.483-1.500; p = 0.578).
      CONCLUSIONS: Brachytherapy should be considered an essential component of
      definitive chemoradiotherapy for the treatment of neuroendocrine cervical cancer.
      Chemotherapy timing, however, does not impact outcome.

PMID- 27720205
TI  - A novel conformal superficial high-dose-rate brachytherapy device for the
      treatment of nonmelanoma skin cancer and keloids.
AB  - PURPOSE: To develop a novel conformal superficial brachytherapy (CSBT) device as
      a treatment option for the patient-specific radiation therapy of conditions
      including superficial lesions, postsurgical positive margins, Dupuytren's
      contractures, keloid scars, and complex anatomic sites (eyelids, nose, ears,
      etc.). METHODS AND MATERIALS: A preliminary CSBT device prototype was designed,
      built, and tested using readily available radioactive seeds. Iodine-125 (125I)
      seeds were independently guided to the treatment surface to conform to the
      target. Treatment planning was performed via BrachyVision Planning System (BPS)
      and dose distributions measured with Gafchromic EBT3 film. Percent depth dose
      curves and profiles for Praseodymium-142 (142Pr), and Strontium-90/Yttrium-90
      (90Sr-90Y) were also investigated as potential sources. Results achieved with
      90Sr-90Y and electron external beam radiation therapy were compared and Monte
      Carlo N-Particle eXtended 2.6 simulations of 142Pr seeds were validated. RESULTS:
      BPS was able to predict clinical dose distributions for a multiple seeds matrix.
      Calculated and measured doses for the 125I seed matrix were 500 cGy and 473.5 cGy
      at 5 mm depth, and 171.0 cGy and 201.0 cGy at 10 mm depth, respectively. Results
      of 90Sr-90Y tests demonstrate a more conformal dose than electron EBRT (1.6 mm
      compared to 4.3 mm penumbra). Measured 142Pr doses were 500 cGy at surface and
      17.4 cGy at 5 mm depth. CONCLUSIONS: The CSBT device provides a highly conformal
      dose to small surface areas. Commercially available BPS can be used for treatment
      planning, and Monte Carlo simulation can be used for plans using beta-emitting
      sources and complex anatomies. Various radionuclides may be used in this device
      to suit prescription depths and treatment areas.

PMID- 27720206
TI  - Performance of the Verigene(r) enteric pathogens test, Biofire FilmArrayTM
      gastrointestinal panel and Luminex xTAG(r) gastrointestinal pathogen panel for
      detection of common enteric pathogens.
AB  - BACKGROUND: Multiplex syndromic panels have the capability of identifying causes
      of diarrheal illness. This study evaluated the performance characteristics of
      three multiplex molecular assays for the detection of common stool pathogens.
      METHODS: A total of 152 stool specimens were tested using three platforms:
      Verigene Enteric Pathogens Test (Verigene), Biofire FilmArray Gastrointestinal
      Panel (Biofire) and Luminex xTAG(r) Gastrointestinal Pathogen Panel (Luminex).
      Assays were assessed only for the targets common among all three; namely,
      Campylobacter, Salmonella, Shigella, Shiga toxin-producing E. coli (STEC),
      norovirus, and rotavirus. RESULTS: The sensitivities (%) and specificities (%) of
      the assays were: Campylobacter, Biofire (100,100), Verigene (83.3,99.3), Luminex
      (91.7,100); Salmonella, Biofire (95.8,100), Verigene (83.3,100), Luminex
      (79.2,100); Shigella, Biofire (100,100), Verigene (95.4,99.1), Luminex (100,100);
      STEC, Biofire (100,100), Verigene (91.7,100), Luminex (91.7,100); norovirus,
      Biofire (94.7,99.3), Verigene (89.0,100), Luminex (89.5,100); and rotavirus,
      Biofire (100, 98.6), Verigene (71.4,100), Luminex (100,100). CONCLUSIONS: All
      multiplex panels detected the majority of gastrointestinal pathogens when
      compared to conventional methods.

PMID- 27720207
TI  - Identification, antimicrobial resistance and molecular characterization of the
      human emerging pathogen Streptococcus gallolyticus subsp. pasteurianus.
AB  - This study aimed to retrospectively identify 22Streptococcus bovis clinical
      strains based on the new taxonomy, as well as to investigate their antibiotic
      resistance and clonality. Strains were identified by Phoenix100 system, 16S rRNA
      sequencing, and two MALDI-TOF MS platforms (Bruker Biotyper, Vitek MS).
      Antibiotic resistance was determined both phenotypically and genotypically, and
      clonality was assessed by PFGE. Most of strains (63.6%) were isolated from urine,
      and diabetes was the most common underlying disease (31.8%). Phoenix100 system
      revealed all strains belonged to biotype II, and 16S rRNA sequencing identified
      all strains as S. gallolyticus subsp pasteurianus (SGSP). Although both MALDI-TOF
      MS systems correctly identified isolates to the species level, only Bruker
      Biotyper accurately identified to the subspecies level. Erythromycin-resistant
      strains (31.8%) were also clindamycin-resistant and positive for erm(B). Strains
      resistant to tetracycline (68.2%) were also resistant to erythromycin. PFGE
      showed high genetic variability identifying 17 different pulsotypes, most of
      which single.

PMID- 27720208
TI  - Clinical characteristics and treatment outcomes of pulmonary disease caused by
      Mycobacterium chimaera.
AB  - Mycobacterium chimaera is a recently described species distinct from M.
      intracellulare. M. chimaera is regarded as less virulent than M. intracellulare.
      Using multi-locus sequence-based identification, M. chimaera lung disease was
      diagnosed in 11 patients. Clinical characteristics and outcomes of M. chimaera
      lung disease were comparable to M. intracellulare lung disease.

PMID- 27720209
TI  - Decreasing prevalence of heterogeneous vancomycin-intermediate Staphylococcus
      aureus among blood isolates in Korean hospitals.
AB  - We investigated the prevalence of heterogeneous vancomycin-intermediate
      Staphylococcus aureus (hVISA) among methicillin-resistant S. aureus (MRSA) blood
      isolates collected from Korean hospitals. The hVISA prevalence in Korean
      hospitals has decreased during the past decade and the most significant decrease
      of hVISA prevalence was observed among the ST5 MRSA.

PMID- 27720211
TI  - History of His bundle pacing.
AB  - Chronic right ventricular (RV) pacing has been shown over the years to exert
      detrimental physiological changes including increased risk for heart failure and
      atrial fibrillation. His bundle pacing offers the promise of physiological
      activation of the ventricular tissue, with the potential for reducing the
      detrimental effects of RV pacing. We describe His bundle pacing in a historical
      context and briefly highlight several clinical trials that have helped shape the
      landscape of permanent His bundle pacing.

PMID- 27720210
TI  - Measuring fear of falling among high-risk, urban, community-dwelling older
      adults.
AB  - Fear of falling (FOF) creates a psychological barrier to performing activities
      for many older adults. The negative impact of fear of falling increases risk of
      curtailment of activities, future falls, and injury. The specific aim for this
      study was to investigate the relationship between two fear of falling measures
      used in clinical research, the FOF Likert scale and Falls Self Efficacy Scale
      International (FES-I). The study included a convenience sample of 107 high-risk,
      community-dwelling, mostly Black (94%) members from one Program for All-Inclusive
      Care for the Elderly program. The FOF scale is one-item asking to rate overall
      concern about falling, while the FES-I is 16-items rating concern about falling
      during physical and social activities. One-way ANOVA and Kruskal-Wallis were
      highly significant (F-value = 22.25, R-squared = 0.39, p < 0.0001). The Graded
      Response Model statistics demonstrated one underlying latent factor, fear of
      falling. This study supports the use of both tools for thorough FOF measurement.

PMID- 27720212
TI  - Introduction: 50 years of evolution of contraceptive medicine.
AB  - The science of contraceptive medicine and reproductive medicine are similar. At
      present contraceptive medicine has moved beyond understanding the mechanism of
      action of steroid hormones with the introduction of many safe and effective
      methods. Long-acting reversible contraceptives are increasing in acceptance and
      providing very high efficacy. The science has pivoted toward optimization of
      family planning in selected high-risk populations, such as those with a high-risk
      of thrombosis, as well as addressing the challenge of obesity. The pipeline for
      male and female related methods will continue to advance the science and public
      health impact.

PMID- 27720214
TI  - [Ultrasound-guided facet block].

PMID- 27720215
TI  - From Precaution to Peril: Public Relations Across Forty Years of Genetic
      Engineering.
AB  - The Asilomar conference on genetic engineering in 1975 has long been pointed to
      by scientists as a model for internal regulation and public engagement. In 2015,
      the organizers of the International Summit on Human Gene Editing in Washington,
      DC looked to Asilomar as they sought to address the implications of the new
      CRISPR gene editing technique. Like at Asilomar, the conveners chose to limit the
      discussion to a narrow set of potential CRISPR applications, involving
      inheritable human genome editing. The adoption by scientists in 2015 of an
      Asilomar-like script for discussing genetic engineering offers historians the
      opportunity to analyze the adjustments that have been made since 1975, and to
      identify the blind spots that remain in public engagement. Scientists did take
      important lessons from the fallout of their limited engagement with public
      concerns at Asilomar. Nonetheless, the scientific community has continued to
      overlook some of the longstanding public concerns about genetic engineering, in
      particular the broad and often covert genetic modification of food products.

PMID- 27720213
TI  - microRNA Therapeutics in Cancer - An Emerging Concept.
AB  - MicroRNAs (miRNAs) are an evolutionarily conserved class of small, regulatory non
      coding RNAs that negatively regulate protein coding gene and other non-coding
      transcripts expression. miRNAs have been established as master regulators of
      cellular processes, and they play a vital role in tumor initiation, progression
      and metastasis. Further, widespread deregulation of microRNAs have been reported
      in several cancers, with several microRNAs playing oncogenic and tumor
      suppressive roles. Based on these, miRNAs have emerged as promising therapeutic
      tools for cancer management. In this review, we have focused on the roles of
      miRNAs in tumorigenesis, the miRNA-based therapeutic strategies currently being
      evaluated for use in cancer, and the advantages and current challenges to their
      use in the clinic.

PMID- 27720216
TI  - Impact of a harbour construction on the benthic community of two shallow marine
      caves.
AB  - Marine caves are unique and vulnerable habitats, threatened by multiple global
      and local disturbances. Whilst the effects of climate change on marine caves have
      already been investigated, no information exists about the effects of local human
      impacts, such as coastal development, on these habitats. This study investigated
      the impact of the construction of a touristic harbour on two shallow underwater
      marine caves in the Ligurian Sea (NW Mediterranean). As a standard methodology
      for monitoring marine caves does not exist yet, changes over time on the benthic
      community were assessed adopting two different non-taxonomic descriptors: trophic
      guilds and growth forms. Harbour construction caused an increase of sediment load
      within the caves, with a consequent decline of filter feeder organisms. Abundance
      of small organisms, such as encrusting and flattened sponges, was greatly reduced
      in comparison to organisms with larger and erect growth forms, such as domed
      mounds and pedunculated sponges. Our study indicated that growth forms and
      trophic guilds are effective descriptors for evaluating changes over time in
      marine caves, and could be easily standardised and applied in monitoring plans.
      In addition, as the harbour construction impacted differently according to the
      cave topography, the use of a systematic sampling in different zones of an
      underwater cave is recommended.

PMID- 27720218
TI  - Management and environmental risk study of the physicochemical parameters of
      ballast water.
AB  - Shipping is a vital industry for the global economy. Stability of ships, provided
      by ballast water, is a crucial factor for cargo loading and unloading processes.
      Ballast water treatment has practical significance in terms of environmental
      issues, ecosystem, and human health, because ships discharge this water into the
      environment before loading their cargos. This study reviews the common methods
      for ballast water management - exchange, heating, filtration, ultrasonic
      treatment, ultraviolet irradiation, chemicals, and gas supersaturation - to
      select the best one. This study compares water temperature, salinity, dissolved
      oxygen, polycyclic aromatic hydrocarbons (PAHs), and heavy metals (Co, Cr, Ni,
      Pb) for ballast tanks of selected ships with the recipient port environment in
      the Persian Gulf as a case study. The exchange of ballast water in the ocean
      and/or its treatment on board to prevent inadvertent effects on the environment's
      physicochemical conditions is related to vessel characteristics, legislation, and
      the environmental condition. Ecological risk study showed that the salt content
      in ballast water is close to that of seawater, but the values of Cr (2.1mg/l) and
      Ni (0.029mg/l) in ballast water are higher than those in seawater (1 and
      0.004mg/l, respectively).

PMID- 27720219
TI  - Mental health indicators fifty years later: A population-based study of men with
      histories of child sexual abuse.
AB  - Childhood sexual abuse (CSA) is a widely acknowledged trauma that affects a
      substantial number of boys/men and has the potential to undermine mental health
      across the lifespan. Despite the topic's importance, few studies have examined
      the long-term effects of CSA on mental health in middle and late life for men.
      Most empirical studies on the effects of CSA have been conducted with women, non
      probability samples, and samples of young or emerging adults with inadequate
      control variables. Based on complex trauma theory, the current study
      investigated: a) the effect of CSA on mental health outcomes (depressive
      symptoms, somatic symptom severity, hostility) in late life for men, and b) the
      moderating effects of childhood adversities and masculine norms in the
      relationship between CSA and the three mental health outcomes. Using a population
      based sample from the 2004-2005 Wisconsin Longitudinal Study, multivariate
      analyses found that CSA was positively related to both depressive and somatic
      symptoms and increased the likelihood of hostility for men who reported a history
      of CSA. Both childhood adversities and masculine norms were positively related to
      the three outcomes for the entire sample. Among CSA survivors, childhood
      adversities exerted a moderating effect in terms of depressive symptoms. Mental
      health practitioners should include CSA and childhood adversities in assessment
      and treatment with men. To more fully understand the effects of CSA, future
      studies are needed that use longitudinal designs, compare male and female
      survivors, and examine protective mechanisms such as social support.

PMID- 27720220
TI  - Alphablockers and 5 alpha-reductase inhibitors, before or after meals? Do they
      interact with alcohol?

PMID- 27720221
TI  - Concurrent gemcitabine and radiotherapy for the treatment of muscle-invasive
      bladder cancer: A pooled individual data analysis of eight phase I-II trials.
AB  - PURPOSE: Although radical cystectomy is still considered the standard of care for
      most localized muscle-invasive bladder cancer (MIBC) patients, bladder-sparing
      strategies with chemoradiotherapy have demonstrated comparable local control and
      survival rates when adjusting for tumor stage. We present a pooled analysis of
      individual patient data out of published trials with gemcitabine-based
      chemoradiotherapy for MIBC. METHODS AND MATERIALS: Individual patient data were
      collected from Institutions that enrolled patients into trials that evaluated
      gemcitabine-based chemoradiotherapy for MIBC. RESULTS: We identified eight
      studies published on gemcitabine-based radiochemotherapy and 190 patients were
      included in this analysis. A complete response (CR) was observed in 166 patients
      (93%). After a median follow up of 44.5months, 36 patients (18.9%) presented a
      bladder recurrence and 14 subsequently underwent cystectomy. The 5-year overall
      survival (OS), disease-specific survival (DSS), and cystectomy-free survival
      (CFS) rates were 59%, 80.9%, and 93.3%, respectively. The achievement of CR after
      chemoradiotherapy was the main prognostic variable which was associated with
      improved OS, DSS, and CFS. The treatment was well tolerated. CONCLUSION: This
      pooled analysis strengthens the evidence that chemoradiotherapy regimens with
      concurrent gemcitabine are feasible and well tolerated. Prospective randomized
      controlled trials are on-going to definitively assess the efficacy of gemcitabine
      based chemoradiotherapy for MIBC.

PMID- 27720223
TI  - Bariatric surgery and intellectual disability: Furthering evidence-based
      practice.
AB  - BACKGROUND: Rates of morbid obesity are higher for individuals with intellectual
      disability (ID). Individuals with ID may find nutritional guidelines difficult to
      follow and many face personal and environmental barriers for physical activity.
      Bariatric surgery may reduce obesity related health comorbidities while promoting
      sustained weight loss in diverse populations. Yet no study has reviewed the
      feasibility of conducting bariatric surgery on individuals with ID. OBJECTIVES:
      To conduct a scoping review of literature on bariatric procedures performed on
      individuals with ID. METHODS: Authors searched electronic database via PubMED,
      Science Direct, Wiley and Medline (1975-2014). Extracted articles were evaluated
      independently following scoping reviews guidelines. RESULTS: Reviewers included
      sixteen studies. Nine surgical interventions were reported on 49 patients with
      ID. Studies followed either case report or case series design. The most common
      procedure patients received was biliopancreatic diversion (n = 24) followed by
      Roux-en-Y Gastric Bypass (n = 12). Degree of weight loss was the primary outcome
      in each study. Excess weight loss (%EWL) ranged from 12% to 86%. Further benefits
      included improved quality of life, decreased psychological tension within family
      and resolution of sleep apnea, hypertension, respiratory distress and type II
      diabetes. Six studies included a post-operative follow-up period below two years.
      CONCLUSIONS: Bariatric surgery may be a viable option to treat obesity in
      individuals with ID but there is no consensus which procedure is preferred and
      which associated interventions should be in place to warrant long lasting
      results. Further research featuring randomized control trials may be beneficial.

PMID- 27720222
TI  - Intestinal barrier dysfunction in human necrotizing enterocolitis.
AB  - BACKGROUND: Intestinal barrier dysfunction has been implicated in necrotizing
      enterocolitis (NEC), but has not been directly measured in human NEC. METHODS:
      Small intestines removed during surgery were immediately mounted in an Ussing
      chamber. mRNA expression of tight junction (TJ) proteins was measured with RT
      PCR. RESULTS: Fifteen infants were included, 5 with NEC and 10 with other
      diagnoses. Average transepithelial resistance (TER) was 11.61+/-1.65Omega/cm2 in
      NEC specimens, 23.36+/-1.48Omega/cm2 at resection margin, and 46.48+/
      5.65Omega/cm2 in controls. Average flux of permeability marker mannitol was
      0.23+/-0.06MUMol/cm2 per h in NEC, 0.04+/-0.01 MUMol/cm2 per h at resection
      margin, and 0.017+/-0.004 MUMol/cm2 per h in control tissue (p<0.05). RT-PCR
      analysis showed marked decrease in mRNA expression of a TJ protein occludin in
      NEC affected tissue (p<0.03 vs. control). Additionally, mRNA expression of myosin
      light chain kinase (MLCK), an important regulator of TJ permeability, was
      increased in NEC specimens. CONCLUSION: These studies show for the first time
      that NEC intestinal tissue have increased intestinal permeability, even at
      grossly healthy-appearing resection areas. The increase in intestinal
      permeability in NEC appeared to be related in part to a decrease in occludin and
      an increase in MLCK expression. LEVEL OF EVIDENCE: Level 2.

PMID- 27720225
TI  - Corrigendum to "State of the art of biological processes for coal gasification
      wastewater treatment" [Biotechnol. Adv. 34/5 (2016) 1064-1072].

PMID- 27720224
TI  - Genome organization of the vg1 and nodal3 gene clusters in the allotetraploid
      frog Xenopus laevis.
AB  - Extracellular factors belonging to the TGF-beta family play pivotal roles in the
      formation and patterning of germ layers during early Xenopus embryogenesis. Here,
      we show that the vg1 and nodal3 genes of Xenopus laevis are present in gene
      clusters on chromosomes XLA1L and XLA3L, respectively, and that both gene
      clusters have been completely lost from the syntenic S chromosome regions. The
      presence of gene clusters and chromosome-specific gene loss were confirmed by
      cDNA FISH analyses. Sequence and expression analyses revealed that paralogous
      genes in the vg1 and nodal3 clusters on the L chromosomes were also altered
      compared to their Xenopus tropicalis orthologs. X. laevis vg1 and nodal3 paralogs
      have potentially become pseudogenes or sub-functionalized genes and are expressed
      at different levels. As X. tropicalis has a single vg1 gene on chromosome XTR1,
      the ancestral vg1 gene in X. laevis appears to have been expanded on XLA1L. Of
      note, two reported vg1 genes, vg1(S20) and vg1(P20), reside in the cluster on
      XLA1L. The nodal3 gene cluster is also present on X. tropicalis chromosome XTR3,
      but phylogenetic analysis indicates that nodal3 genes in X. laevis and X.
      tropicalis were independently expanded and/or evolved in concert within each
      cluster by gene conversion. These findings provide insights into the function and
      molecular evolution of TGF-beta family genes in response to
      allotetraploidization.

PMID- 27720226
TI  - Circadian-Time Sickness: Time-of-Day Cue-Conflicts Directly Affect Health.
AB  - A daily rhythm that is not in synchrony with the environmental light-dark cycle
      (as in jetlag and shift work) is known to affect mood and health through an as
      yet unresolved neural mechanism. Here, we combine Bayesian probabilistic 'cue
      conflict' theory with known physiology of the biological clock of the brain,
      entailing the insight that, for a functional pacemaker, it is sufficient to have
      two interacting units (reflecting environmental and internal time-of-day cues),
      without the need for an extra homuncular directing unit. Unnatural light-dark
      cycles cause a time-of-day cue-conflict that is reflected by a desynchronization
      between the ventral (environmental) and dorsal (internal) pacemaking signals of
      the pacemaker. We argue that this desynchronization, in-and-of-itself, produces
      health issues that we designate as 'circadian-time sickness', analogous to
      'motion sickness'.

PMID- 27720229
TI  - Experimental method to characterize the strain dependent permeability of tissue
      engineering scaffolds.
AB  - Permeability is an overarching mechanical parameter encompassing the effects of
      porosity, pore size, and interconnectivity of porous structures. This parameter
      directly influences transport of soluble particles and indirectly regulates fluid
      pressure and velocity in tissue engineering scaffolds. The permeability also
      contributes to the viscoelastic behavior of visco-porous material under loading
      through frictional drag mechanism. We propose a straightforward experimental
      method for permeability characterization of tissue engineering scaffolds. In the
      developed set-up a step-wise spacer was designed to facilitate measurement of the
      permeability under different compressive strains while maintaining similar
      experimental conditions during the successive measurements. As illustration of
      the method, we measured the permeability of scaffolds presenting different
      average pore sizes and subjected to different compression values. Results showed
      an exponential relationship between the permeability and the average pore size of
      the scaffolds. Furthermore, the trend of the permeability decrease with
      compressive strains was depending on pore sizes of the scaffolds. The
      permeability also appeared to play a role in relaxation behavior of the
      scaffolds.

PMID- 27720227
TI  - Both intrinsic and extrinsic apoptotic pathways are involved in Toll-like
      receptor 4 (TLR4)-induced cell death in monocytic THP-1 cells.
AB  - Our previous study showed that TLR3 induces apoptosis via both death receptors
      and mitochondial in human endothelial cells. We report here that the activation
      of TLR4 induced dose- and time-dependent cell death in moncytic THP-1 cells. LPS
      treatment of THP-1 cells induced the activation of both caspase 8 and 9,
      suggesting the involvement of intrinsic and extrinsic apoptosis pathways.
      TNFalpha was induced by TLR4 activation at both mRNA and protein levels, but its
      neutralization did not down-regulated TLR4-induced cell death. TLR4 activation
      also induced the up-regulation of TRAIL and its receptors DR4 and DR5, and the
      neutralization of TRAIL ameliorated TLR4 induced apoptosis, suggesting the
      involvement of TRAIL and its receptors DR4 and DR5 in LPS-induced cell death.
      Meanwhile, LPS treatment down-regulated the expression of FLICE inhibitory
      protein (FLIP), a suppressor of death receptor-induced cell death. In addition,
      TLR4 activation down-regulated the anti-apoptotic protein bcl-2, and up-regulated
      the pro-apoptotic proteins Noxa and Puma, suggesting that mitochondrial apoptotic
      pathway was also involved in LPS-induced cell death. Furthermore, we found that
      TAP63alpha might confer to the activation of intrinsic and extrinsic apoptotic
      pathways. The treatment of THP-1 cells with LPS induced the translocation of
      TAP63alpha from cytoplasm to nucleus. Taken together, our study suggested that
      both death receptors and mitochondial were involved in TLR4-induced cell death,
      and TAP63alpha may be a target for the prevention of LPS-induced cell death.

PMID- 27720228
TI  - Postoperative time dependent tibiofemoral articular cartilage contact kinematics
      during step-up after ACL reconstruction.
AB  - This study was to investigate the in vivo tibiofemoral cartilage contact
      locations before and after anterior cruciate ligament (ACL) reconstruction at 6
      and 36 months. Ten patients with unilateral ACL injury were included. A step-up
      motion was analyzed using a combined magnetic resonance modeling and dual
      fluoroscopic imaging techniques. The preoperative (i.e. ACL deficient and healthy
      contralateral) and postoperative cartilage contact locations at 6 and 36 months
      were analyzed. Similar patterns of the cartilage contact locations during the
      step-up motion were found for the preoperative and postoperative knee states as
      compared to the preoperative healthy contralateral side. At the end of step-up
      motion, the medial contact locations at postoperative 36 months were more
      anterior when compared to the preoperative healthy contralateral (p=0.02) and 6
      months postoperative knee states (p=0.01). The changes of the cartilage contact
      locations at 36 months after ACL reconstruction compared to the healthy
      contralateral side were strongly correlated with the changes at 6 months
      postoperatively. This study showed that the tibiofemoral cartilage contact
      locations of the knee changes with time after ACL reconstruction, implying an
      ongoing recovery process within the 36 months after the surgery. There could be
      an association between the short-term (6 months) and longer-term (36 months)
      contact kinematics after ACL reconstruction. Future studies need to investigate
      the intrinsic relationship between knee kinematics at different times after ACL
      reconstruction.

PMID- 27720230
TI  - Neuropeptide Y accelerates post-fracture bone healing by promoting osteogenesis
      of mesenchymal stem cells.
AB  - Fracture repair is a complex yet well orchestrated regenerative process involving
      numerous signaling and cell types including osteoblasts. Here we showed that NPY,
      a neurotransmitter with regulatory functions in bone homeostasis, may contribute
      to the post-fracture bone healing in patients with traumatic brain injury
      fracture combined injuries. Our results suggested NPY levels were increased in
      patients with the combined injuries, accomplished by arising of bone healing
      markers, such as ALP, OC, PICP and ICTP, than in those with simple fractures, and
      NPY have direct actions on MSCs to promote their osteogenic differentiation. Our
      results provided clinical evidences for NPY participating in the bone healing
      process in a nonhypothalamic manner, most probably by directly promoting
      osteogenesis of mesenchymal stem cells.

PMID- 27720231
TI  - The association between reproductive and hormonal factors and ovarian cancer by
      estrogen-alpha and progesterone receptor status.
AB  - OBJECTIVE: We assessed the association between reproductive and hormonal factors
      and ovarian cancer incidence characterized by estrogen receptor-alpha (ERalpha)
      and progesterone receptor (PR) status. METHODS: Tissue microarrays were used to
      assess ERalpha and PR expression among 197 Nurses' Health Study (NHS), 42 NHSII
      and 76 New England Case-Control Study (NECC) ovarian cancer cases. NHS/NHSII
      cases were matched to up to 4 controls (n=954) on diagnosis date and birth year.
      NECC controls (n=725) were frequency matched on age. Cases were considered
      receptor positive if >=1% of tumor cells stained positive. Associations by
      ERalpha and PR status were assessed using polytomous logistic regression. p-Value
      for heterogeneity was calculated using a likelihood ratio test. RESULTS: 45% of
      ovarian tumors were PR(+), 78% were ERalpha(+) and 45% were ERalpha(+)/PR(+),
      while 22% were ERalpha(-)/PR(-). Postmenopausal status was associated with an
      increased risk of PR(-) tumors (OR: 2.07; 95%CI: 1.15-3.75; p-heterogeneity=0.01)
      and age at natural menopause was inversely associated with PR(-) tumors (OR, per
      5years: 0.77; 95%CI: 0.61-0.96; p-het=0.01). Increasing duration of postmenopause
      was differentially associated by PR status (p-het=0.0009). Number of children and
      tubal ligation were more strongly associated with ERalpha(-) versus ERalpha(+)
      tumors (p-het=0.002 and 0.05, respectively). No differential associations were
      observed for oral contraceptive or hormone therapy use. CONCLUSIONS:
      Postmenopausal women have an increased risk of developing PR(-) ovarian tumors
      compared to premenopausal women. The associations observed for ovarian cancer
      differ from those seen for breast cancer suggesting that the biology for tumor
      development through ERalpha and PR pathways may differ.

PMID- 27720233
TI  - Are Antibiotics Necessary for Dental Pain Without Overt Infection?

PMID- 27720232
TI  - Distance from a Comprehensive Cancer Center: A proxy for poor cervical cancer
      outcomes?
AB  - OBJECTIVE: To evaluate the potential relationship between outcomes in cervical
      cancer patients based on distance from our Comprehensive Cancer Center (CCC).
      METHODS: A retrospective cohort study of cervical cancer patients was performed.
      Abstracted data included: demographics, clinicopathologic variables, treatment,
      and survival. Analyses both by quartiles and distance <100 and >=100miles from
      our institution were performed. Data were analyzed using SAS version 9.2.
      RESULTS: 390 patients living a median distance of 58.1miles (range 1.2-571miles)
      from our CCC were identified. Patients were generally white (n=249), non-smokers
      (n=226), with Stage IB disease (n=222), squamous histology (n=295) and underwent
      primary surgical therapy (n=229). Patients were divided into both quartiles as
      well as two strata: <100 and >=100miles for comparison. Progression-free survival
      (PFS) and overall survival (OS) favored patients living closer to our center with
      a lower median OS for patients living >=100miles (65.4vs. 99.4months; p=0.040).
      Cox proportional hazard modeling noted that advanced stage was predictive of
      inferior PFS and OS, while other clinical covariates including age, BMI, race,
      smoking status and histology had a variable impact on outcomes and distance
      >100miles was associated with a higher risk of death (hazard ratio [HR]=1.68, 95%
      confidence interval [CI] 1.11-2.54). CONCLUSION: Overall survival for patients
      living >100miles from our CCC was worse when compared to patients in closer
      proximity. Outreach efforts and utilization of navigators may help decrease the
      impact of geographic and racial disparities on outcomes.

PMID- 27720235
TI  - Perioperative Risk in Patients With Epilepsy Undergoing Total Joint Arthroplasty.
AB  - BACKGROUND: Epilepsies is a spectrum of brain disorders ranging from severe, life
      threatening, and disabling to more benign, but little is known about its impact
      in the perioperative arthroplasty setting. We sought to determine whether
      epileptic patients undergoing elective total joint arthroplasty (TJA) would be at
      increased risk for in-hospital complications and death, prolonged stay, and
      nonroutine discharge. METHODS: Using discharge records from the Nationwide
      Inpatient Sample (2002-2011), we identified 6,054,344 patients undergoing
      elective primary TJA, of whom 31,865 (0.5%) were identified as having epilepsy.
      Comparisons of perioperative outcomes were performed by multivariable logistic
      regression modeling. RESULTS: Patients with epilepsy were associated with
      increased in-hospital mortality (odds ratio [OR] 2.03, 95% confidence interval
      [CI] 1.57-2.62) and morbidity, including (in decreasing order of magnitude of
      effect estimate): mechanical ventilation (OR 1.74, 95% CI 1.56-1.94), induced
      mental disorder (OR 1.70, 95% CI 1.56-1.85), stroke (OR 1.63, 95% CI 1.23-2.15),
      pneumonia (OR 1.34, 95% CI 1.21-1.49), and ileus or gastrointestinal events (OR
      1.26, 95% CI 1.12-1.42). Epilepsy was associated with higher risk for blood
      transfusion (OR 1.30, 95% CI 1.27-1.33), prolonged hospital stay (OR 1.14, 95% CI
      1.11-1.17), and nonroutine discharge (OR 1.54, 95% CI 1.50-1.58). We found no
      association with inpatient thromboembolic events, acute renal failure, and
      myocardial infarction. CONCLUSION: Patients with epilepsy are at increased risk
      for early postoperative complications (especially mechanical ventilation, induced
      mental disorder, and stroke) and resource utilization after elective joint
      arthroplasty. Greater awareness of epilepsy and its health consequences may
      contribute to improvements in the perioperative management of TJA patients.

PMID- 27720234
TI  - Metabolic control of immune tolerance in health and autoimmunity.
AB  - The filed that links immunity and metabolism is rapidly expanding. The adipose
      tissue, by secreting a series of immune regulators called adipokines, represents
      the common mediator linking metabolic processes and immune system functions. The
      dysregulation of adipokine secretion, occurring in obese individuals or in
      conditions of malnutrition or dietary restriction, affects the activity of immune
      cells resulting in inflammatory autoimmune responses or increased susceptibility
      to infectious diseases. Alterations of cell metabolism that characterize several
      autoimmune diseases strongly support the idea that the immune tolerance is also
      regulated by metabolic pathways. The comprehension of the molecular mechanisms
      underlying these alterations may lead to the development of novel therapeutic
      strategies to control immune cell differentiation and function in conditions of
      autoimmunity.

PMID- 27720236
TI  - Evaluation of foot position and orientation as manipulated variables to control
      external knee adduction moments in leg extension training.
AB  - BACKGROUND AND OBJECTIVE: Effective leg extension training at a leg press
      requires high forces, which need to be controlled to avoid training-induced
      damage. In order to avoid high external knee adduction moments, which are one
      reason for unphysiological loadings on knee joint structures, both training
      movements and the whole reaction force vector need to be observed. In this study,
      the applicability of lateral and medial changes in foot orientation and position
      as possible manipulated variables to control external knee adduction moments is
      investigated. As secondary parameters both the medio-lateral position of the
      center of pressure and the frontal-plane orientation of the reaction force vector
      are analyzed. METHODS: Knee adduction moments are estimated using a dynamic model
      of the musculoskeletal system together with the measured reaction force vector
      and the motion of the subject by solving the inverse kinematic and dynamic
      problem. Six different foot conditions with varying positions and orientations of
      the foot in a static leg press are evaluated and compared to a neutral foot
      position. RESULTS: Both lateral and medial wedges under the foot and medial and
      lateral shifts of the foot can influence external knee adduction moments in the
      presented study with six healthy subjects. Different effects are observed with
      the varying conditions: the pose of the leg is changed and the direction and
      center of pressure of the reaction force vector is influenced. Each effect
      results in a different direction or center of pressure of the reaction force
      vector. CONCLUSIONS: The results allow the conclusion that foot position and
      orientation can be used as manipulated variables in a control loop to actively
      control knee adduction moments in leg extension training.

PMID- 27720237
TI  - Novel volatiles of skin-borne bacteria inhibit the growth of Gram-positive
      bacteria and affect quorum-sensing controlled phenotypes of Gram-negative
      bacteria.
AB  - The skin microbiota is import for body protection. Here we present the first
      comprehensive analysis of the volatile organic compound (VOC) profiles of typical
      skin-resident corynebacterial and staphylococcal species. The VOC profile of
      Staphylococcus schleiferi DSMZ 4807 was of particular interest as it is dominated
      by two compounds, 3-(phenylamino)butan-2-one and 3-(phenylimino)butan-2-one
      (schleiferon A and B, respectively). Neither of these has previously been
      reported from natural sources. Schleiferon A and B inhibited the growth of
      various Gram-positive species and affected two quorum-sensing-dependent
      phenotypes - prodigiosin accumulation and bioluminescence - of Gram-negative
      bacteria. Both compounds were found to inhibit the expression of prodigiosin
      biosynthetic genes and stimulate the expression of prodigiosin regulatory genes
      pigP and pigS. This study demonstrates that the volatile schleiferons A and B
      emitted by the skin bacterium S. schleiferi modulate differentially and
      specifically its interactions with members of diverse bacterial communities. A
      network of VOC-mediated interspecies interactions and communications must be
      considered in the establishment of the (skin) microbiome and both compounds are
      interesting candidates for further investigations to better understand how VOCs
      emitted by skin bacteria influence and modulate the local microbiota and
      determine whether they are relevant to antibiotic and anti-virulence therapies.

PMID- 27720238
TI  - [Cross sectional study of comorbidities and concomitant medications in a cohort
      of human immunodeficiency virus-infected patients].
AB  - AIM: To assess the prevalence of comorbidities, concomitant therapies and adverse
      effects associated with the medication in a cohort of patients with HIV
      infection. DESIGN: Multicentre cross-sectional study. SETTINGS: Infectious
      Diseases or Internal Medicine outpatient Clinics of 3 hospitals in the Basque
      Country. PARTICIPANTS: During a 3 month period, patients with the following
      inclusion criteria were randomly selected: HIV infection, age>18years,
      antiretroviral treatment (ART) for at least 6months, and no changes in ART in the
      previous 4weeks. A total of 224 patients (of the 225 expected) were included.
      MEASUREMENTS: Data were collected using a form, and include, epidemiological and
      anthropometric data, data related to HIV infection, comorbidities, current
      therapies, and adverse effects. RESULTS: Of the 224 patients, 95.5% had at least
      one comorbidity, the most common being HCV infection (51.3%), dyslipidaemia
      (37.9%), diabetes mellitus or impaired fasting glucose (21.9%), and hypertension
      (21.9%). A total of 155 patients (69.2%) were taking concomitant medication:
      anxiolytics (21.4%), antihypertensives (19.6%), proton pump inhibitors (17.9%),
      statins (17%), and antidepressants (16.5%). Adverse effects (AE) were observed in
      62.9% of subjects, the most common being, changes in body fat distribution
      (32.6%) and gastrointestinal (24.1%). CONCLUSIONS: Patients with HIV infection
      are getting older, with more comorbidities, with very frequent use of concomitant
      treatments, and high number of adverse effects. This requires a multidisciplinary
      approach and a coordinated effort within the Primary Care setting.

PMID- 27720239
TI  - Guidelines on prevention of healthcare-associated infection in neonates and
      children.

PMID- 27720240
TI  - Reply to: 'Guidelines on prevention of healthcare-associated infection in
      neonates and children'.

PMID- 27720241
TI  - Firearm Injury Prevention in Clinical Practice: Staying on Message.

PMID- 27720242
TI  - Handgrip Strength and Ideal Cardiovascular Health among Colombian Children and
      Adolescents.
AB  - OBJECTIVE: To evaluate the association between handgrip strength and ideal
      cardiovascular health (CVH) in Colombian children and adolescents. STUDY DESIGN:
      During the 2014-2015 school years, we examined a cross-sectional component of the
      FUPRECOL (Association for Muscular Strength with Early Manifestation of
      Cardiovascular Disease Risk Factors among Colombian Children and Adolescents)
      study. Participants included 1199 (n = 627 boys) youths from Bogota (Colombia).
      Handgrip strength was measured with a standard adjustable hand held dynamometer
      and expressed relative to body mass (handgrip/body mass) and as absolute values
      in kilograms. Ideal CVH, as defined by the American Heart Association, was
      determined as meeting ideal levels of the following components: 4 behaviors
      (smoking status, body mass index, cardiorespiratory fitness, and diet) and 3
      factors (total cholesterol, blood pressure, and glucose). RESULTS: Higher levels
      of handgrip strength (both absolute and relative values) were associated with a
      higher frequency of ideal CVH metrics in both sexes (P for trend <= .001). Also,
      higher levels of handgrip strength were associated with a greater number of ideal
      health behaviors (P for trend < .001 in both boys and girls), and with a higher
      number of ideal health factors in boys (P for trend < .001). Finally, levels of
      handgrip strength were similar between ideal versus nonideal glucose or total
      cholesterol groups in girls. CONCLUSIONS: Handgrip strength was strongly
      associated with ideal CVH in Colombian children and adolescents, and thus
      supports the relevance of early targeted interventions to promote strength
      adaptation and preservation as part of primordial prevention.

PMID- 27720243
TI  - Quality of Life in Type 1 Diabetes and Celiac Disease: Role of the Gluten-Free
      Diet.
AB  - OBJECTIVE: To evaluate quality of life (QoL) and glycemic control in youth with
      type 1 diabetes (T1D) and celiac disease vs T1D only. We hypothesized that QoL
      scores would be lower in youth with T1D and celiac disease and those nonadherent
      to the gluten-free diet (GFD). STUDY DESIGN: This case control study included 35
      youth with T1D and 35 with T1D  and  celiac disease matched for age, sex,
      diabetes duration, and hemoglobin A1c level. QoL was assessed in participants and
      parents using the Pediatric Quality of Life Inventory Generic Core Scale,
      Pediatric Quality of Life Inventory Diabetes Module. and the General Well-Being
      Scale; youth with T1D and celiac disease also completed the celiac disease
      specific DUX questionnaire and parents completed the Pediatric Quality of Life
      Inventory Family Impact Scale. Questionnaires were scored from 0 to 100; higher
      scores indicate better QoL or well-being. Scores were compared between T1D vs T1D
      with celiac disease, with subgroup analysis by GFD adherence vs nonadherence and
      therapy (continuous subcutaneous insulin infusion vs multiple daily injections).
      RESULTS: Youth with T1D  and celiac disease reported similar generic and diabetes
      specific QoL to T1D only. GFD nonadherent vs adherent youth reported lower
      diabetes-specific QoL (mean score 58 vs 75, P = .003) and lower general well
      being (57 vs 76, P = .02), as did their parents (50 vs 72, P = .006), and
      hemoglobin A1c was higher (9.6% vs 8.0%, P = .02). Youth with T1D  and  celiac
      disease using continuous subcutaneous insulin infusion vs multiple daily
      injections had similar generic and diabetes-specific QoL and A1C (8.6 vs 8.2%, P
      = .44), but were less happy having to follow a lifelong diet (59 vs 29, P =
      .007). CONCLUSIONS: Youth with T1D  and celiac disease who do not adhere to the
      GFD have lower QoL and worse glycemic control. Novel strategies are required to
      understand and improve adherence in those with both conditions.

PMID- 27720244
TI  - Child- and Parent-Reported Health: The Rashomon Effect of Multiple Realities.

PMID- 27720245
TI  - Progressive Cervical Spinal Cord Atrophy after a Traffic Accident.

PMID- 27720247
TI  - Time-lapse embryo imaging and morphokinetic profiling: Towards a general
      characterisation of embryogenesis.
AB  - In vitro fertilisation is an effective method of assisted reproductive technology
      in both humans and certain non-human animal species. In most species,
      specifically, in humans and livestock, high in vitro fertilisation success rates
      are achieved via the transfer of embryos with the highest implantation and
      subsequent developmental potential. In order to reduce the risk of multiple
      gestation, which could be a result of the transfer of several embryos per cycle,
      restrictive transfer policies and methods to improve single embryo selection have
      been implemented. A non-invasive alternative to standard microscopic observation
      of post-fertilisation embryo morphology and development is time-lapse technology;
      this enables continuous, uninterrupted observation of embryo development from
      fertilisation to transfer. Today, there are several time-lapse devices that are
      commercially available for clinical use, and methods in which time-lapse could be
      used to improve embryology are continually being assessed. Here we review the use
      of time-lapse technology in the characterisation of embryogenesis and its role in
      embryo selection. Furthermore, the prospect of using this technology to identify
      aneuploidy in human embryos, as well as the use of time-lapse to improve
      embryological procedures in agriculturally important species such as the pig and
      cow are discussed.

PMID- 27720246
TI  - Extra-central nervous system target for assessment and treatment in refractory
      anti-N-methyl-d-aspartate receptor encephalitis.
AB  - Anti-N-methyl-d-aspartate-type glutamate receptor autoimmune encephalitis can
      arise in the setting of ovarian teratoma and often responds to resection. When it
      occurs in the absence of tumor, failure to respond to treatment may be more
      likely, and affected patients often require intensive care. To further understand
      the mechanisms and potential management, we present findings from an autopsy
      conducted on a young woman who died of refractory autoimmune encephalitis of this
      type. Rituximab was administered 70 days before death, and both 37 and 14 days
      before death, CD19+ lymphocytes were only 0.1% of blood cells. Ten sessions of
      plasmapheresis were performed after rituximab treatment. Nonetheless, the
      autoantibodies were present in serum 4 days before death, demonstrating ongoing
      antibody production. The hippocampus and medial temporal lobe demonstrated
      inflammation with T cell and prominent microglial involvement, but no plasma
      cells or plasmablasts were found there, or anywhere in the brain, despite an
      extensive search. Examination of lymph node tissue identified many plasma cells
      along sinusoids. These findings demonstrate that the antibody-producing cells are
      long-lived and can reside in lymphoid tissue. Awareness of continuing antibody
      production, the extra-central nervous system site, the indication for cytotoxic
      therapy, and the potential for biopsy assessment may lead to more effective
      treatment.

PMID- 27720250
TI  - Differentiating the sources of fine sediment, organic matter and nitrogen in a
      subtropical Australian catchment.
AB  - Understanding the sources of sediment, organic matter and nitrogen (N)
      transferred from terrestrial to aquatic environments is important for managing
      the deleterious off-site impacts of soil erosion. In particular, investigating
      the sources of organic matter associated with fine sediment may also provide
      insight into carbon (C) and N budgets. Accordingly, the main sources of fine
      sediment, organic matter (indicated by total organic carbon), and N are
      determined for three nested catchments (2.5km2, 75km2, and 3076km2) in
      subtropical Australia. Source samples included subsoil and surface soil, along
      with C3 and C4 vegetation. All samples were analysed for stable isotopes
      (delta13C, delta15N) and elemental composition (TOC, TN). A stable isotope mixing
      model (SIAR) was used to determine relative source contributions for different
      spatial scales (nested catchments), climatic conditions and flow stages. Subsoil
      was the main source of fine sediment for all catchments (82%, SD=1.15) and the
      main N source at smaller scales (55-76%, SD=4.6-10.5), with an exception for the
      wet year and at the larger catchment, where surface soil was the dominant N
      source (55-61%, SD=3.6-9.9), though contributions were dependent on flow (59
      680m3/s). C3 litter was the main source of organic C export for the two larger
      catchments (53%, SD=3.8) even though C4 grasses dominate the vegetation cover in
      these catchments. The sources of fine sediment, organic matter and N differ in
      subtropical catchments impacted by erosion, with the majority of C derived from
      C3 leaf litter and the majority of N derived from either subsoil or surface soil.
      Understanding these differences will assist management in reducing sediment,
      organic matter and N transfers in similar subtropical catchments while providing
      a quantitative foundation for testing C and N budgets.

PMID- 27720248
TI  - Allergen-specific IgE to food molecular components and age: From early childhood
      to adulthood.
AB  - BACKGROUND: Respiratory allergy is characterised by an IgE-mediated reaction. The
      immune system functions, including IgE production, progressively decline over
      time with growing up and ageing. Molecular-based allergy diagnostic defines
      sensitisation profile. This study aimed to evaluate the impact of age on serum
      allergen-specific IgE to molecular component levels in a large sample of
      subjects. METHODS: Serum IgE to: rCor a11, rPru p3, nJug r3, rAra h8, rGly m4,
      rCor a8, nPen m1, nAct d8, Bos d 8, and nGal d2 were assessed by ISAC method.
      Sera from 2795 patients, 1234 males (44.1%) and 1561 females (55.9%), median age
      23 years (1st and 3rd quartiles: 9.7-43.7 years; age range: 1 month-103 years)
      were analysed. RESULTS: The number of positive tests (i.e. sensitisation) tended
      to increase between birth and school-age until young adulthood and then
      decreased. A similar age-dependent trend was observed considering the levels of
      each allergen components: the levels of each allergen component tended to
      increase until early adulthood, but Gal d 2 and Bos d 8 (rapidly diminishing),
      and then to decrease over time. However, the pattern is significantly dependent
      on each single tested food. CONCLUSIONS: Allergen-specific IgE production to food
      molecular components tend to reduce with ageing, but with differences between
      allergens. This phenomenon should be adequately evaluated managing allergic
      patients.

PMID- 27720249
TI  - Assessment of the performance of SMFCs in the bioremediation of PAHs in
      contaminated marine sediments under different redox conditions and analysis of
      the associated microbial communities.
AB  - The biodegradation of naphthalene, 2-methylnaphthalene and phenanthrene was
      evaluated in marine sediment microbial fuel cells (SMFCs) under different
      biodegradation conditions, including sulfate reduction as a major biodegradation
      pathway, employment of anode as terminal electron acceptor (TEA) under inhibited
      sulfate reducing bacteria activity, and combined sulfate and anode usage as
      electron acceptors. A significant removal of naphthalene and 2-methylnaphthalene
      was observed at early stages of incubation in all treatments and was attributed
      to their high volatility. In the case of phenanthrene, a significant removal
      (93.83+/-1.68%) was measured in the closed circuit SMFCs with the anode acting as
      the main TEA and under combined anode and sulfate reduction conditions (88.51+/
      1.3%). A much lower removal (40.37+/-3.24%) was achieved in the open circuit
      SMFCs operating with sulfate reduction as a major biodegradation pathway.
      Analysis of the anodic bacterial community using 16S rRNA gene pyrosequencing
      revealed the enrichment of genera with potential exoelectrogenic capability,
      namely Geoalkalibacter and Desulfuromonas, on the anode of the closed circuit
      SMFCs under inhibited SRB activity, while they were not detected on the anode of
      open circuit SMFCs. These results demonstrate the role of the anode in enhancing
      PAHs biodegradation in contaminated marine sediments and suggest a higher system
      efficiency in the absence of competition between microbial redox processes (under
      SRB inhibition), namely due to the anode enrichment with exoelectrogenic
      bacteria, which is a more energetically favorable mechanism for PAHs oxidation
      than sulfate.

PMID- 27720251
TI  - Elimination of the antibiotic norfloxacin in municipal wastewater, urine and
      seawater by electrochemical oxidation on IrO2 anodes.
AB  - The electrochemical degradation of the fluoroquinolone antibiotic norfloxacin
      (NOR) on Ti/IrO2 anodes, in several aqueous matrices was evaluated. For this
      purpose, initially the performance and degradation routes of the technology at
      several pH values (3.0, 6.5, 7.5 and 9.0) and in the presence of some of the most
      common anions in real water matrices (Cl-, HCO3-, SO42- and NO3-) were
      determined. The results showed that the degradation of NOR can occur through both
      direct elimination at the electrode surface and mediated oxidation, via the
      electrogeneration of oxidative agents, such as active chlorine species and
      percarbonate ions, which come from chloride and bicarbonate oxidation,
      respectively. Conversely, nitrate ions showed to inhibit the efficiency of the
      system. Concerning the pH, the efficiency of the process in the presence of
      chloride ions followed the order: 9.0>7.5>6.5>3.0; showing a strong dependence of
      the NOR speciation, and being the anionic form of the antibiotic the more
      susceptible to be oxidized. Furthermore, the identification of three primary NOR
      by-products demonstrated that the initial attack of the active chlorine species,
      mainly HOCl, occurred at the secondary amine of the piperazine ring followed by
      chlorination of the benzene ring. The precedent findings were crucial to
      understand the efficiency of the technology to eliminate NOR in synthetic complex
      matrices such as seawater, municipal wastewater and urine. The electrochemical
      oxidation showed to be promissory to eliminate NOR, and its associated
      antimicrobial activity, in such complexes matrices. Waters at basic pH containing
      chloride or bicarbonate ions, such as seawater or municipal wastewater showed to
      be the most adapted to the application of the technology. Additionally, nitrate
      ions or urea, found in some matrices like fresh urine, reduce the efficiency of
      the process.

PMID- 27720252
TI  - A framework for planning sustainable seawater desalination water supply.
AB  - A quantitative framework for sustainable desalination planning in metropolitan
      areas, which integrates the tools of mixed integer linear programming and life
      cycle assessment, is presented. The life cycle optimisation framework allows for
      optimal desalination planning by considering choices over intake type, staging
      and location of the infrastructure under different land-use, environmental and
      economic policies. Optimality is defined by the decision maker's selected
      objective function, being either an environmental impact or a levelised cost
      indicator. The framework was tested for future desalination planning scenarios in
      the northern metropolitan area of Perth, Western Australia. Results indicate that
      multi-staged construction and decentralised planning solutions may produce lower
      life cycle environmental impacts (58%) and at a lower levelised cost (24%) than a
      centralised desalination solution currently being considered by Western
      Australian water planners. Sensitivity analysis results suggest that the better
      environmental and economic performance of decentralised planning over centralised
      planning is highly sensitive to the proportion of land that can be made available
      for the siting of decentralised plants near the demand zone. Insight into land
      use policies is a critical factor to the initiation and success of decentralised
      solution in developed metropolitan areas.

PMID- 27720253
TI  - Biomonitoring of genotoxic effects and elemental accumulation derived from air
      pollution in community urban gardens.
AB  - Urban gardening is a growing global phenomenon with a positive impact on society.
      Despite several associated benefits, growing vegetables in urban gardens that are
      localized in highly polluted areas poses questions about the safety of the
      produced food. Therefore, the identification of risk factors that result in
      possible deleterious effects to human health is important for realizing all of
      the benefits to society. We evaluated the use of two biomonitoring methods in ten
      urban gardens of Sao Paulo city and one control site: the micronuclei frequencies
      for early tetrads of Tradescantia pallida (Rose) Hunt. cv. "Purpurea" Boom
      (hereafter, Trad-MCN) as a short-term indicator of genotoxic response and tree
      barks to quantify the accumulation of traffic-related chemical elements as a long
      term biomarker of air pollution in urban gardens. Mature plants of Tradescantia
      pallida were exposed in each garden, and their inflorescences were sampled over
      three months. A random set of 300 early tetrads in 13 to 21 slides per garden
      were evaluated for micronuclei frequencies. Elemental concentrations in 428 tree
      barks samples from 107 different trees in the areas surrounding urban gardens
      were quantified using an energy dispersive X-ray fluorescence spectrometer. The
      frequency of Trad-MCN has a significant correlation with traffic variables and
      chemical elements related to road dust and tailpipe emissions deposited in tree
      barks. Negative associations between Trad-MCN and both the distance through
      traffic and the presence of vertical obstacles were observed in the community
      gardens. The Mn/Zn concentrations in tree barks were associated with increased
      Trad-MCN.

PMID- 27720254
TI  - The application of iron-based technologies in uranium remediation: A review.
AB  - Remediating uranium contamination is of worldwide interest because of the
      increasing release of uranium from mining and processing, nuclear power leaks,
      depleted uranium components in weapons production and disposal, and phosphate
      fertilizer in agriculture activities. Iron-based technologies are attractive
      because they are highly efficient, inexpensive, and readily available. This paper
      provides an overview of the current literature that addresses the application of
      iron-based technologies in the remediation of sites with elevated uranium levels.
      The application of iron-based materials, the current remediation technologies and
      mechanisms, and the effectiveness and environmental safety considerations of
      these approaches were discussed. Because uranium can be reduced and reoxidized in
      the environment, the review also proposes strategies for long-term in situ
      remediation of uranium. Unfortunately, iron-based materials (nanoscale zerovalent
      iron and iron oxides) can be toxic to microorganisms. As such, further studies
      exploring the links among the fates, ecological impacts, and other
      environmentally relevant factors are needed to better understand the constraints
      on using iron-based technologies for remediation.

PMID- 27720255
TI  - Low-drift nozzles vs. standard nozzles for pesticide application in the
      biological efficacy trials of pesticides in apple pest and disease control.
AB  - The coarse spray air-induction nozzles have documented pesticide drift reducing
      potential and hence pose lower risk of environmental pollution than the standard
      fine spray hollow cone nozzles. However, it is questioned that use of the low
      drift nozzles might not provide as effective crop protection as the standard
      nozzles. The objective of work was to assess the pest and disease control
      efficacy as affected by spray volume rate and nozzle type. The experiment was
      carried out in apple orchard, cv Jonagold/M26. The evaluated treatments were
      combinations of three spray volume rates: 250, 500 and 750lha-1, and two types of
      nozzles: hollow cone nozzles generating very fine spray, and flat fan air
      induction nozzles producing coarse droplets. The biological performance of
      treatments was determined based on severity of diseases: apple scab (Venturia
      inaequalis), powdery mildew (Podosphaera leucotricha) and bull's eye rot
      (Pezicula spp.), as well as population or damage caused by pests: green apple
      aphid (Aphis pomi), rosy apple aphid (Dysaphis plantaginea Pass.), woolly apple
      aphid (Eriosoma lanigerum), apple rust mite (Aculus schlechtendali) and apple
      blossom weevil (Anthonomus pomorum L.). In general apple scab was equally
      controlled by all treatments. Only in the years of high infection pressure
      efficacy of powdery mildew control was better for fine spray nozzles and high
      volume rates. Green and rosy apple aphids were better controlled with higher
      volume rates, though significance of the advantage over the lower rates was
      occasional. No effect of spray quality on efficacy of aphid and mite control was
      found for any spray volume rate. Better control of apple blossom weevil and
      woolly apple aphid was achieved with the high spray volume rate providing heavy
      coverage to the point of run-off. The air induction nozzles having drift reducing
      potential are biologically efficacious alternative to conventional hollow cone
      nozzles.

PMID- 27720256
TI  - Hydrological and thermal effects of hydropeaking on early life stages of
      salmonids: A modelling approach for implementing mitigation strategies.
AB  - Alterations in hydrological and thermal regimes can potentially affect salmonid
      early life stages development and survival. The dewatering of salmon spawning
      redds due to hydropeaking can lead to mortality in early life stages, with higher
      impact on the alevins as they have lower tolerance to dewatering than the eggs.
      Flow-related mitigation measures can reduce early life stage mortality. We
      present a set of modelling tools to assess impacts and mitigation options to
      minimise the risk of mortality in early life stages in hydropeaking rivers. We
      successfully modelled long-term hydrological and thermal alterations and
      consequences for development rates. We estimated the risk of early life stages
      mortality and assessed the cost-effectiveness of implementing three release
      related mitigation options (A,B,C). The economic cost of mitigation was low and
      ranged between 0.7% and 2.6% of the annual hydropower production. Options
      reducing the flow during spawning (B and C) in addition to only release minimum
      flows during development (A) were considered more effective for egg and alevin
      survival. Options B and C were however constraint by water availability in the
      system for certain years, and therefore only option A was always feasible. The
      set of modelling tools used in this study were satisfactory and their
      applications can be useful especially in systems where little field data is
      available. Targeted measures built on well-informed modelling tools can be tested
      on their effectiveness to mitigate dewatering effects vs. the hydropower system
      capacity to release or conserve water for power production. Environmental flow
      releases targeting specific ecological objectives can provide better cost
      effective options than conventional operational rules complying with general
      legislation.

PMID- 27720257
TI  - The drinking water contamination crisis in Flint: Modeling temporal trends of
      lead level since returning to Detroit water system.
AB  - Since Flint returned to its pre-crisis source of drinking water close to 25,000
      water samples have been collected and tested for lead and copper in >10,000
      residences. This paper presents the first analysis and time trend modeling of
      lead data, providing new insights about the impact of this intervention. The
      analysis started with geocoding all water lead levels (WLL) measured during an 11
      month period following the return to the Detroit water supply. Each data was
      allocated to the corresponding tax parcel unit and linked to secondary datasets,
      such as the composition of service lines, year built, or census tract poverty
      level. Only data collected on residential parcels within the City limits were
      used in the analysis. One key feature of Flint data is their collection through
      two different sampling initiatives: (i) voluntary or homeowner-driven sampling
      whereby concerned citizens decided to acquire a testing kit and conduct sampling
      on their own (non-sentinel sites), and (ii) State-controlled sampling where data
      were collected bi-weekly at selected sites after training of residents by
      technical teams (sentinel sites). Temporal trends modeled from these two datasets
      were found to be statistically different with fewer sentinel data exceeding WLL
      thresholds ranging from 10 to 50MUg/L. Even after adjusting for housing
      characteristics the odds ratio (OR) of measuring WLL above 15MUg/L at non
      sentinel sites is significantly >1 (OR=1.480) and it increases with the threshold
      (OR=2.055 for 50MUg/L). Joinpoint regression showed that the city-wide percentage
      of WLL data above 15MUg/L displayed four successive trends since the return to
      Detroit Water System. Despite the recent improvement in water quality, the
      culprit for differences between sampling programs needs to be identified as it
      impacts exposure assessment and might influence whether there is compliance or
      not with the Lead and Copper Rule.

PMID- 27720258
TI  - Abnormal increase of Mn and TP concentrations in a temperate reservoir during
      fall overturn due to drought-induced drawdown.
AB  - Due to global warming, some regions of Earth may face frequent and severe
      droughts in the future, leading to the deterioration of surface water quality. In
      this study, we investigated the effects of drought-induced drawdown on the water
      quality of the Zhoucun Reservoir, Shandong Province, East China, during the fall
      overturn. Field surveys were conducted during stratification (April-November)
      over three standard years 2012, 2013, and 2014, and over the El Nino event of
      2015. Temporal and vertical variations of the physical and chemical indexes were
      investigated during monitoring. Results show that after the formation of
      stratification, the hypolimnion rapidly shifted to anaerobic conditions, with the
      accumulation of pollutants such as manganese (Mn) and total phosphorous (TP). Due
      to the extreme El Nino event in 2015, both the upper and lower metalimnion limits
      moved down along with the water level in summer, which resulted in the transfer
      of hypolimnion water to the metalimnion. In summer 2015, large amounts of
      pollutants were measured in the metalimnion: a phenomenon that did not occur at
      the same period of the standard years. At the beginning of the overturn in 2015,
      the water quality of the whole reservoir deteriorated when the metalimnion water
      shifted to the epilimnion. Mn and TP concentrations in the epilimnion reached
      0.202mg/L and 0.086mg/L, respectively, which are significantly higher than those
      in the standard years. Although the tributary rivers entered the epilimnion of
      the reservoir during the overturn, Mn and TP concentrations of the inflow were
      only of 0.049-0.072mg/L and 0.033-0.047mg/L, respectively, indicating that these
      rivers were not the source of the high TP and high Mn concentrations in the
      epilimnion. Hence, we conclude that more attention should be paid to the
      metalimnion position and the vertical distribution of pollutants when studying
      lakes and reservoirs experiencing droughts.

PMID- 27720259
TI  - TGF-beta1 promotes linear invadosome formation in hepatocellular carcinoma cells,
      through DDR1 up-regulation and collagen I cross-linking.
AB  - Transforming growth factor-beta1 (TGF-beta1) is an important player in chronic
      liver diseases inducing fibrogenesis and hepatocellular carcinoma (HCC)
      development. TGF-beta1 promotes pleiotropic modifications at the cellular and
      matrix microenvironment levels. TGF-beta1 was described to enhance production of
      type I collagen and its associated cross-linking enzyme, the lysyl oxidase-like2
      (LOXL2). In addition, TGF-beta1 and type I collagen are potent inducers of
      invadosomes. Indeed, type I collagen fibers induce the formation of active linear
      invadosomes through the discoidin domain receptor 1 (DDR1). The goal of our study
      was to address the role of TGF-beta1 in collagen cross-linking and its impact on
      the formation of linear invadosomes in liver cancer cells. We first report a
      significant correlation between expressions of TGF-beta1, and type I collagen,
      LOXL2, DDR1 and MT1-MMP in human HCCs. We demonstrate that TGF-beta1 promotes a
      Smad4-dependent up-regulation of DDR1, together with LOXL2, in cultured HCC
      cells. Moreover, we show that LOXL2-induced collagen cross-linking enhances
      linear invadosome formation. Altogether, our data demonstrate that TGF-beta1
      favors linear invadosome formation through the expressions of both the inducers,
      such as collagen and LOXL2, and the components such as DDR1 and MT1-MMP of linear
      invadosomes in cancer cells. Meanwhile, our data uncover a new TGF-beta1
      dependent regulation of DDR1 expression.

PMID- 27720261
TI  - Health inequalities: Mexico's greatest challenge.

PMID- 27720260
TI  - Dissonant health transition in the states of Mexico, 1990-2013: a systematic
      analysis for the Global Burden of Disease Study 2013.
AB  - BACKGROUND: Child and maternal health outcomes have notably improved in Mexico
      since 1990, whereas rising adult mortality rates defy traditional epidemiological
      transition models in which decreased death rates occur across all ages. These
      trends suggest Mexico is experiencing a more complex, dissonant health transition
      than historically observed. Enduring inequalities between states further
      emphasise the need for more detailed health assessments over time. The Global
      Burden of Diseases, Injuries, and Risk Factors Study 2013 (GBD 2013) provides the
      comprehensive, comparable framework through which such national and subnational
      analyses can occur. This study offers a state-level quantification of disease
      burden and risk factor attribution in Mexico for the first time. METHODS: We
      extracted data from GBD 2013 to assess mortality, causes of death, years of life
      lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years
      (DALYs), and healthy life expectancy (HALE) in Mexico and its 32 states, along
      with eight comparator countries in the Americas. States were grouped by
      Marginalisation Index scores to compare subnational burden along a socioeconomic
      dimension. We split extracted data by state and applied GBD methods to generate
      estimates of burden, and attributable burden due to behavioural, metabolic, and
      environmental or occupational risks. We present results for 306 causes, 2337
      sequelae, and 79 risk factors. FINDINGS: From 1990 to 2013, life expectancy from
      birth in Mexico increased by 3.4 years (95% uncertainty interval 3.1-3.8), from
      72.1 years (71.8-72.3) to 75.5 years (75.3-75.7), and these gains were more
      pronounced in states with high marginalisation. Nationally, age-standardised
      death rates fell 13.3% (11.9-14.6%) since 1990, but state-level reductions for
      all-cause mortality varied and gaps between life expectancy and years lived in
      full health, as measured by HALE, widened in several states. Progress in women's
      life expectancy exceeded that of men, in whom negligible improvements were
      observed since 2000. For many states, this trend corresponded with rising YLL
      rates from interpersonal violence and chronic kidney disease. Nationally, age
      standardised YLL rates for diarrhoeal diseases and protein-energy malnutrition
      markedly decreased, ranking Mexico well above comparator countries. However, amid
      Mexico's progress against communicable diseases, chronic kidney disease burden
      rapidly climbed, with age-standardised YLL and DALY rates increasing more than
      130% by 2013. For women, DALY rates from breast cancer also increased since 1990,
      rising 12.1% (4.6-23.1%). In 2013, the leading five causes of DALYs were
      diabetes, ischaemic heart disease, chronic kidney disease, low back and neck
      pain, and depressive disorders; the latter three were not among the leading five
      causes in 1990, further underscoring Mexico's rapid epidemiological transition.
      Leading risk factors for disease burden in 1990, such as undernutrition, were
      replaced by high fasting plasma glucose and high body-mass index by 2013.
      Attributable burden due to dietary risks also increased, accounting for more than
      10% of DALYs in 2013. INTERPRETATION: Mexico achieved sizeable reductions in
      burden due to several causes, such as diarrhoeal diseases, and risks factors,
      such as undernutrition and poor sanitation, which were mainly associated with
      maternal and child health interventions. Yet rising adult mortality rates from
      chronic kidney disease, diabetes, cirrhosis, and, since 2000, interpersonal
      violence drove deteriorating health outcomes, particularly in men. Although state
      inequalities from communicable diseases narrowed over time, non-communicable
      diseases and injury burdens varied markedly at local levels. The dissonance with
      which Mexico and its 32 states are experiencing epidemiological transitions might
      strain health-system responsiveness and performance, which stresses the
      importance of timely, evidence-informed health policies and programmes linked to
      the health needs of each state. FUNDING: Bill & Melinda Gates Foundation,
      Instituto Nacional de Salud Publica.

PMID- 27720262
TI  - Management of right coronary artery fistula caused by nail gun trauma.

PMID- 27720264
TI  - The American Association for Thoracic Surgery 2016 ethics forum: Working virtues
      in surgical practice.
AB  - Moral virtues are the complement to ethical principles. They constitute the
      elements of character that drive habits and daily routines. Certain virtues are
      especially important in surgery, shaping surgical practice even when no big
      decisions are at hand. Eight virtues are described and the work they do is
      explored: trustworthiness, equanimity, empathy, advocacy, compassion, courage,
      humility, and hope.

PMID- 27720263
TI  - Characteristics and outcomes of patients with postoperative cardiovascular
      pseudoaneurysms.
AB  - BACKGROUND: Data regarding long-term outcomes in cardiovascular pseudoaneurysms
      are sparse. In patients with prior cardiovascular surgery, we sought to assess
      characteristics and outcomes in patients with cardiovascular pseudoaneurysms
      (excluding ischemic left ventricular pseudoaneurysms). METHODS: We included 114
      patients (mean age, 57 +/- 16 years; 70% were men) with prior cardiovascular
      surgery who presented with paravalvular (n = 71, 59 aortic and 12 mitral valve)
      and ascending aortic (n = 43) pseudoaneurysms (27% with systemic infection).
      Baseline, surgical, and follow-up data were recorded. A composite end point of
      stroke or death during follow-up was recorded. RESULTS: Additive European System
      for Cardiac Operative Risk Evaluation was high (10%), and 81% of patients
      underwent another redo cardiovascular surgery. Over a mean follow-up period of
      5.2 +/- 4 years, there were 37 (32%) composite events (32 deaths and 5 strokes).
      Within the surgical subgroup, there were 10 (11%) composite events during the in
      hospital stay. The 1-, 2-, 5-, and 10-year freedom from composite events were
      86%, 82%, 74%, and 55%, respectively. Additive European System for Cardiac
      Operative Risk Evaluation (hazard ratio, 1.14) and presence of a documented
      systemic infection (hazard ratio, 3.90) were associated with a higher rate of
      composite events, whereas subsequent cardiovascular surgery as a time-dependent
      covariate hazard ratio (hazard ratio, 0.30) was associated with improved freedom
      from composite events (all P < .05). CONCLUSIONS: Patients with a history of
      cardiovascular surgery in whom cardiovascular pseudoaneurysms subsequently
      develop have a high rate of short- and long-term adverse events. A higher
      additive European System for Cardiac Operative Risk Evaluation and documented
      systemic infection were associated with a higher rate of composite events,
      whereas cardiovascular surgery (to correct cardiovascular pseudoaneurysms) during
      follow-up was associated with improved freedom from adverse events.

PMID- 27720265
TI  - Brain parenchymal fraction in an age-stratified healthy population - determined
      by MRI using manual segmentation and three automated segmentation methods.
AB  - BACKGROUND AND PURPOSE: Brain atrophy is a prominent feature in many
      neurodegenerative diseases, such as multiple sclerosis, but age-related decrease
      of brain volume occurs regardless of pathological neurodegeneration. Changes in
      brain volume can be described by use of the brain parenchymal fraction (BPF),
      most often defined as the ratio of total brain parenchyma to total intracranial
      space. The BPF is of interest both in research and in clinical practice. To be
      able to properly interpret this variable, the normal range of BPF must be known.
      The objective of this study is to present normal values for BPF, stratified by
      age, and compare manual BPF measurement to three automated methods. MATERIALS AND
      METHODS: The BPFs of 106 healthy individuals aged 21 to 85 years were determined
      by the automated segmentation methods SyMap, VBM8 and SPM12. In a subgroup of 54
      randomly selected individuals, the BPF was also determined by manual
      segmentation. RESULTS: The median (IQR) BPFs of the whole study population were
      0.857 (0.064), 0.819 (0.028) and 0.784 (0.073) determined by SyMap, VBM8 and
      SPM12, respectively. The BPF decreased with increasing age. The correlation
      coefficients between manual segmentation and SyMap, VBM8 and SPM12 were 0.93
      (P<0.001), 0.77 (P<0.001) and 0.56 (P<0.001), respectively. CONCLUSIONS: There
      was a clear relationship between increasing age and decreasing BPF. Knowledge of
      the range of normal BPF in relation to age group will help in the interpretation
      of BPF data. The automated segmentation methods displayed varying degrees of
      similarity to the manual reference, with SyMap being the most similar.

PMID- 27720266
TI  - Burn leads to long-term elevated admissions to hospital for gastrointestinal
      disease in a West Australian population based study.
AB  - BACKGROUND: While the most obvious impact of burn is on the skin, systemic
      responses also occur after burn, including intestinal inflammation. The objective
      of this study was to assess if burns are associated with increased long-term
      admissions for gastrointestinal diseases. METHODS: A population-based
      longitudinal study using linked hospital morbidity and death data from Western
      Australia was undertaken of adults aged at least 15 years when hospitalized for a
      first burn (n=20,561) in 1980-2012. A frequency matched non-injury comparison
      cohort was randomly selected from Western Australia's birth registrations and
      electoral roll (n=80,960). Crude admission rates and summed days in hospital for
      digestive diseases were calculated. Negative binomial and Cox proportional
      hazards regression modeling were used to generate incidence rate ratios (IRR) and
      hazard ratios (HR), respectively. RESULTS: After adjustment for demographic
      factors and pre-existing health status, the burn cohort had 1.54 times (95%
      confidence interval (CI): 1.47-1.62) as many admissions and almost three times
      the number of days in hospital with a digestive system diagnosis (IRR, 95% CI:
      2.90, 2.60-3.25) than the uninjured cohort. Significantly elevated adjusted post
      burn incident rates were identified, with the risk decreasing with increasing
      time: in the first month (HR, 95% CI: 3.02, 1.89-4.82), from one month to five
      years (HR, 95% CI: 1.42, 1.31-1.54), and from five to twenty years after burn
      (HR, 95% CI: 1.13, 1.06-1.20). CONCLUSIONS: Findings of increased hospital
      admission rates and prolonged length of hospital stay for gastrointestinal
      diseases in the burn cohort provide evidence to support that burns have effects
      that persist long after the initial injury.

PMID- 27720267
TI  - Enhancement of stem cell differentiation to osteogenic lineage on hydroxyapatite
      coated hybrid PLGA/gelatin nanofiber scaffolds.
AB  - A combination of polymeric materials and bioceramics has recently received a
      great deal of attention for bone tissue engineering applications. In the present
      study, hybrid nanofibrous scaffolds were fabricated from PLGA and gelatin via
      electrospinning and then were coated with hydroxyapatite (HA). They were then
      characterized and used in stem cell culture studies for the evaluation of their
      biological behavior and osteogenic differentiation in vitro. This study showed
      that all PLGA, hybrid PLGA/gelatin and HA-PLGA/gelatin scaffolds were composed of
      ultrafine fibers with smooth morphology and interconnected pores. The MTT assay
      confirmed that the scaffolds can support the attachment and proliferation of stem
      cells. During osteogenic differentiation, bone-related gene expression, ALP
      activity and biomineralization on HA-PLGA/gelatin scaffolds were higher than
      those observed on other scaffolds and TCPS. PLGA/gelatin electrospun scaffolds
      also showed higher values of these markers than TCPS. Taking together, it was
      shown that nanofibrous structure enhanced osteogenic differentiation of adipose
      tissue derived stem cells. Furthermore, surface-coated HA stimulated the effect
      of nanofibers on the commitment of stem cells toward osteolineage. In conclusion,
      HA-PLGA/gelatin electrospun scaffolds were demonstrated to have significant
      potential for bone tissue engineering applications.

PMID- 27720268
TI  - Development of inactivated poliovirus vaccine from Sabin strains: A progress
      report.
AB  - The Global Polio Eradication Initiative (GPEI) has seen significant progress
      since it began in 1988, largely due to the worldwide use of oral poliovirus
      vaccine (OPV). In order to achieve polio eradication the global cessation of OPV
      is necessary because OPV contains live attenuated poliovirus, which in rare
      circumstances could re-gain wild poliovirus (WPV) characteristics with potential
      to establish transmission. The GPEI endgame strategy for the period 2013-2018
      recommends the globally synchronised sequential cessation of the Sabin strains
      contained in the OPV, starting with type 2 Sabin. The withdrawal of Sabin type 2
      took place in April 2016, with the introduction of at least one dose of
      inactivated poliovirus vaccine (IPV) as a risk mitigation strategy. The
      introduction of IPV into 126 countries since 2013 has required a rapid scale-up
      of IPV production by the two manufacturers supplying the global public sector
      market. This scale-up has been fraught with challenges, resulting in reductions
      of 40-50% of initial supply commitments. Consequently, 22 countries will not be
      supplied until 2018, and another 23 countries will experience serious stock-outs.
      In the last decade repeated calls-for-action were made to the global community to
      invigorate their vision and investment in developing "new poliovirus vaccines"
      including the development of IPV from less-virulent strains, such as Sabin-IPV (S
      IPV). The conventional Salk-IPV production is limited to high-income
      industrialized-country manufacturers due to the containment requirements (i.e.,
      high sanitation, low force-of-poliovirus-infection, and high population
      immunity). The use of Sabin strains in the production of S-IPV carries a lower
      biosafety risk, and was determined to be suitable for production in developing
      countries, expanding the manufacturing base and making IPV more affordable and
      accessible in the long term. Significant progress in the S-IPV has been made
      since 2006. S-IPV is now licensed as S-IPV in Japan and as standalone S-IPV in
      China, demonstrating the feasibility of this vaccine. In addition, production
      process improvements can further reduce the cost of production. The latter are
      critical to the economic success of this vaccine in the global market. We
      summarize the progress made to date in S-IPV technology, the scientific data and
      economic evidence in support of S-IPV development.

PMID- 27720269
TI  - Introduction.

PMID- 27720270
TI  - Use of computer-assisted sperm analysis and flow cytometry to detect seasonal
      variations of bovine semen quality.
AB  - Seasonal fluctuations of climate are considered a major factor affecting
      spermatogenesis and semen quality in the bovine. Our study aimed to investigate
      the effect of season on functional parameters of frozen-thawed bovine semen using
      computer-assisted sperm analysis (CASA) and flow cytometry. For this purpose, 86
      ejaculates were collected from five mature Holstein-Friesian bulls kept under
      subtropical conditions during summer (August to September; n = 43) and winter
      (December to January; n = 43) months. Semen was diluted with a Tris-egg yolk
      based extender and frozen at -196  degrees C. Computer-assisted sperm analysis
      was performed immediately after thawing (0h) and after 3 hours of incubation (3h)
      to evaluate the percentage (%) of total motile, progressively motile, and rapidly
      motile sperm. In addition, the average path, curvilinear, and straight-line
      velocities as well as the amplitude of lateral head displacement of sperm were
      determined. The percentages of sperm with intact plasma membrane and acrosome
      (PMAI, %), with high mitochondrial membrane potential (HMMP, %), with low
      intracellular Ca+2 levels (LOW-Ca+2, %), and with high DNA fragmentation index
      (DFI%, %) were flow cytometrically determined at 0 and 3h. The survival rate of
      sperm under hypotonic conditions (HYPO-SURV, %) and the percentage of sperm with
      inducible acrosome reaction (IAR, %) were assessed using flow cytometry at 0 and
      3h, respectively. The fixed effect of season (winter vs. summer) on the quality
      parameters of sperm was explored by applying linear mixed-effects models. The
      results showed an improvement of all CASA parameters, except for the straight
      line velocity (P > 0.05) in winter compared with summer for both unincubated and
      incubated sperm (P < 0.01 in all cases). Ejaculates collected in summer had lower
      values of IAR (P < 0.001) as well as PMAI, HMMP, and LOW-Ca+2 at 0 and 3h (P <
      0.01 in all cases). On the contrary, HYPO-SURV and DFI% (at 0 and 3h) were not
      affected by season (P > 0.05 in all cases). Concluding, the employment of CASA
      and flow cytometry revealed season-related alterations in the functional status
      of cryopreserved bovine sperm, which suggest an adverse effect of summer heat
      stress on motility, plasma membrane and acrosome integrity, inducibility of
      acrosome reaction, mitochondrial function and intracellular Ca+2 content, but not
      on the DNA integrity of sperm after freezing-thawing.

PMID- 27720271
TI  - Sustained Elevation of Vascular Endothelial Growth Factor and Angiopoietin-2
      Levels After Transcatheter Aortic Valve Replacement.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) exposes the systemic
      vasculature to increased mechanical forces. Endothelial adaptation to mechanical
      stimuli is associated with angiogenic activation through various growth factors.
      We studied the potential angiogenic shift evoked by TAVR. METHODS: From a cohort
      of 69 consecutive patients undergoing TAVR, we excluded patients with conditions
      known to affect angiogenic factors, and serum vascular endothelial growth factor
      (VEGF) and angiopoietin (Ang)-1 and Ang-2 were assessed by ELISA. We assessed in
      vitro the properties of endothelial cells after exposure to serum collected from
      patients undergoing TAVR using adhesion, migration, and Matrigel angiogenesis
      assays. The correlation between changes in angiogenic factors and cardiac
      functions was evaluated on 30- day echocardiograms. RESULTS: The study population
      consisted of 46 patients (82 +/- 5 years). Two days after TAVR the post/pre TAVR
      ratio of VEGF, Ang-1, and Ang-2 was 5.38 +/- 4 (P < 0.001), 1.05 +/- 0.49 (P =
      0.27), and 4.65 +/- 2.01 (P < 0.001), respectively. The increase in VEGF and Ang
      2 showed a significant correlation (r = 0.609; P < 0.001), but no correlation was
      found with hemolysis or tissue injury markers. Patients with relatively low
      levels of VEGF or an Ang-2 rise had more severe aortic stenosis and coronary
      disease at baseline. Exposure of endothelial cells to post-TAVR serum induced
      adhesion, migration, and tube formation compared with pre-TAVR serum. An increase
      in VEGF levels correlated with improvement in pulmonary systolic pressure and a
      right ventricular fractional area change at 30 days, (r = 0.54 and r = 0.48,
      respectively; P < 0.01). CONCLUSIONS: Sustained elevation of VEGF and Ang-2
      levels occur after TAVR, reflecting a systemic angiogenic shift. A rise in VEGF
      levels is associated with a decrease in pulmonary blood pressure in patients
      undergoing TAVR.

PMID- 27720272
TI  - Epicardial Adipose Tissue Volume and Left Ventricular Myocardial Function Using 3
      Dimensional Speckle Tracking Echocardiography.
AB  - BACKGROUND: Although epicardial adipose tissue (EAT) volume is associated with
      increased incidence of coronary artery disease (CAD), its role in myocardial
      systolic dysfunction is unclear. The present study aimed to identify independent
      determinants of EAT volume in patients without obstructive CAD, and to evaluate
      the association between EAT volume (vs other measures of obesity) and myocardial
      systolic strain analysis. METHODS: We prospectively recruited 130 patients
      without obstructive CAD on contrast-enhanced cardiac computed tomography imaging
      and normal left ventricular ejection fraction on 3-dimensional (3D)
      echocardiography. EAT volume was quantified from cardiac computed tomography
      imaging, and 3D multidirectional (longitudinal, circumferential, radial, and
      area) strain were measured. RESULTS: The mean EAT volume was 97.5 +/- 43.7 cm3.
      In multivariable analysis, measures of obesity (body mass index [P = 0.007] and
      waist/hip ratio [P = 0.001]) were independently associated with larger EAT
      volume. EAT volume was correlated with 3D global longitudinal (r = 0.601; P <
      0.001), circumferential (r = 0.375; P < 0.001), radial (r = -0.546; P < 0.001),
      and area (r = 0.558; P < 0.001) strain. In multivariable analyses, epicardial fat
      volume was the strongest predictor of 3D global longitudinal (standardized beta =
      0.512; P < 0.001), circumferential (standardized beta = 0.242; P = 0.006), radial
      (standardized beta = -0.422; P < 0.001), and area (standardized beta = 0.428; P <
      0.001) strain. In contrast, other measures of obesity including body mass index
      and waist/hip ratio were not independent determinants of 3D multidirectional
      global strain (all P > 0.05). CONCLUSIONS: EAT volume is independently associated
      with impaired myocardial systolic function despite preserved 3D left ventricular
      ejection fraction and absence of obstructive CAD, and might play a significant
      role in the pathophysiology of diabetic, obesity, and metabolic heart disease.

PMID- 27720273
TI  - Inflammatory and metabolic responses to dietary intervention differ among
      individuals at distinct cardiometabolic risk levels.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of two
      interventions in breakfast with different fatty acid content on metabolic and
      inflammatory biomarkers in individuals at different cardiovascular risk levels.
      METHODS: This crossover clinical trial included 80 overweight participants who
      were grouped according to the presence of metabolic syndrome (MetS). The
      participants received two isocaloric breakfast interventions for 4 wk, with a 2
      wk washout. The "Brazilian" breakfast was enriched with saturated fat, whereas
      the "modified" meal was enriched with unsaturated fatty acids and fibers.
      Repeated-measures analysis of variance was used to compare dietary data, and
      Student's t or Wilcoxon tests were used to compare clinical and inflammatory
      variables. A chi2 test was employed to compare frequencies. RESULTS: Frequencies
      of MetS increased after the Brazilian breakfast and decreased after the modified
      meal. Significant reduction in mean values of WC and diastolic blood pressure
      (DBP) and elevation in high-density lipoprotein cholesterol were detected at the
      end of the modified intervention. Participants with or without the MetS exhibited
      contrasting responses to the modified breakfast: respectively, significant
      changes in DBP levels (-3.7 +/- 6.9 versus -0.5 +/- 6.9 mm Hg; P < 0.05), plasma
      glucose (-3 +/- 7.3 versus 3 +/- 7.4 mg/dL; P < 0.05), and apolipoprotein-B (-0.1
      +/- 0.6 versus 0.2 +/- 0.3 mg/mL; P < 0.05), interferon-gamma (-0.6 +/- 1.2
      versus 0.1 +/- 1.3 pg/mL; P < 0.05), and tumor necrosis factor-alpha
      concentrations (0.4 +/- 3.6 versus -0.8 +/- 2.8 pg/mL; P < 0.05) were observed.
      CONCLUSIONS: Dietary intervention of small magnitude, for a short period, was
      able to improve traditional risk factors for cardiovascular disease and
      inflammatory markers, as well as the frequency of MetS. Responses to dietary
      interventions of individuals at different levels of cardiovascular risk should be
      examined through different biomarkers.

PMID- 27720274
TI  - Tumor necrosis factor-alpha inhibitor-induced psoriasis: Systematic review of
      clinical features, histopathological findings, and management experience.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) inhibitors have been reported
      to induce new-onset psoriasis. OBJECTIVE: To better define the demographic,
      clinical features, and treatment approach of TNF-alpha inhibitor-induced
      psoriasis. METHODS: Systematic review of published cases of TNF-alpha inhibitor
      induced psoriasis. RESULTS: We identified 88 articles with 216 cases of new-onset
      TNF-alpha inhibitor-induced psoriasis. The mean age at psoriasis onset was 38.5
      years. The most common underlying diseases were Crohn disease (40.7%) and
      rheumatoid arthritis (37.0%). Patients underwent TNF-alpha therapy for an average
      of 14.0 months before psoriasis onset with 69.9% of patients experiencing onset
      within the first year. The majority of patients received skin-directed therapy,
      though patients who discontinued TNF therapy had the greatest resolution of
      symptoms (47.7%) compared with those who switched to a different TNF agent
      (36.7%) or continued therapy (32.9%). LIMITATIONS: Retrospective review that
      relies on case reports and series. CONCLUSION: While TNF-alpha inhibitor
      cessation may result in resolution of induced psoriasis, lesions may persist.
      Decisions regarding treatment should be weighed against the treatability of TNF
      alpha inhibitor-induced psoriasis, the severity of the background rheumatologic
      or gastrointestinal disease, and possible loss of efficacy with cessation
      followed by retreatment. Skin-directed therapy is a reasonable initial strategy
      except in severe cases.

PMID- 27720276
TI  - Variation trends of the postoperative outcomes for unilateral cleft lip patients
      by modified Mohler and Tennison-Randall cheiloplasties.
AB  - PURPOSE: To evaluate postoperative variation trends of unilateral cleft lip by
      stages, and to analyze influential factors of nasolabial symmetry. MATERIALS AND
      METHODS: A total of 145 patients with unilateral cleft lip were treated by the
      modified Mohler or Tennison-Randall technique, and received routine anti-scarring
      treatment postoperatively. Photogrammetry was applied to respectively measure 5
      indices by stages preoperatively, the first week (1 w), the third month (3 m),
      the sixth month (6 m), and the first year (1 y) postoperatively. Then we
      calculated the symmetry ratio and drew line charts. Student t tests were used for
      any group differences; linear regression analysis was used to examine which
      postoperative stage correlated best with the preoperative stage; cluster analysis
      was used to classify the severity of the cleft according to preoperative SRsn
      cphi, which was used to predict the operative difficulty and to select an
      appropriate technique. RESULTS: The Mohler technique yielded a more symmetric
      result. With the Tennison-Randall technique, the alar base was more lateral and
      downward, and the lip height on cleft side seemed longer. A stable effect emerged
      around 1 year after surgery with both techniques. Conspicuous scars appeared at 3
      months, most scars gradually fade at 6 months, and the total evolution took
      around 1 year. Scars from the Mohler technique fluctuated across a larger range.
      Preoperative SRsn-cphi of the two techniques had statistical significance and was
      adopted as the basis for cluster analysis. The critical value was 0.670. The
      Mohler technique attained an almost identical effect in each interval, whereas
      the Tennison-Randall technique was better in the interval that SRsn-cphi <0.670.
      CONCLUSIONS: Preoperative SRsn-cphi can be the evaluation index of severity; the
      modified Mohler technique is more broadly applicable to differences in severity
      than is the Tennison-Randall technique.

PMID- 27720275
TI  - Combined soft and skeletal tissue modelling of normal and dysmorphic midface
      postnatal development.
AB  - BACKGROUND: Midface hypoplasia as exemplified by Treacher Collins Syndrome (TCS)
      can impair appearance and function. Reconstruction involves multiple invasive
      surgeries with variable long-term outcomes. This study aims to describe normal
      and dysmorphic midface postnatal development through combined modelling of
      skeletal and soft tissues and to develop a surgical evaluation tool. MATERIALS
      AND METHODS: Midface skeletal and soft tissue surfaces were extracted from
      computed tomography scans of 52 control and 14 TCS children, then analysed using
      dense surface modelling. The model was used to describe midface growth,
      morphology, and asymmetry, then evaluate postoperative outcomes. RESULTS:
      Parameters responsible for the greatest variation in midface size and shape
      showed differences between TCS and controls with close alignment between skeletal
      and soft tissue models. TCS children exhibited midface dysmorphology and
      hypoplasia when compared with controls. Asymmetry was also significantly higher
      in TCS midfaces. Combined modelling was used to evaluate the impact of surgery in
      one TCS individual who showed normalisation immediately after surgery but
      reversion towards TCS dysmorphology after 1 year. CONCLUSION: This is the first
      quantitative analysis of postnatal midface development using combined modelling
      of skeletal and soft tissues. We also provide an approach for evaluation of
      surgical outcomes, laying the foundations for future development of a
      preoperative planning tool.

PMID- 27720277
TI  - Dosimetric and radiobiological comparison of TG-43 and Monte Carlo calculations
      in 192Ir breast brachytherapy applications.
AB  - PURPOSE: To investigate the clinical significance of introducing model based dose
      calculation algorithms (MBDCAs) as an alternative to TG-43 in 192Ir interstitial
      breast brachytherapy. MATERIALS AND METHODS: A 57 patient cohort was used in a
      retrospective comparison between TG-43 based dosimetry data exported from a
      treatment planning system and Monte Carlo (MC) dosimetry performed using MCNP v.
      6.1 with plan and anatomy information in DICOM-RT format. Comparison was
      performed for the target, ipsilateral lung, heart, skin, breast and ribs, using
      dose distributions, dose-volume histograms (DVH) and plan quality indices
      clinically used for plan evaluation, as well as radiobiological parameters.
      RESULTS: TG-43 overestimation of target DVH parameters is statistically
      significant but small (less than 2% for the target coverage indices and 4% for
      homogeneity indices, on average). Significant dose differences (>5%) were
      observed close to the skin and at relatively large distances from the implant
      leading to a TG-43 dose overestimation for the organs at risk. These differences
      correspond to low dose regions (<50% of the prescribed dose), being less than 2%
      of the prescribed dose. Detected dosimetric differences did not induce clinically
      significant differences in calculated tumor control probabilities (mean absolute
      difference <0.2%) and normal tissue complication probabilities. CONCLUSION: While
      TG-43 shows a statistically significant overestimation of most indices used for
      plan evaluation, differences are small and therefore not clinically significant.
      Improved MBDCA dosimetry could be important for re-irradiation, technique inter
      comparison and/or the assessment of secondary cancer induction risk, where
      accurate dosimetry in the whole patient anatomy is of the essence.

PMID- 27720279
TI  - Bone Marrow Aspirate Evaluation.
AB  - Important steps in bone marrow aspirate evaluation include determining if bone
      marrow evaluation is indicated; using appropriate aspirate collection, smear
      preparation, and staining techniques; and performing a systematic approach for
      the cytologic evaluation. The cytologic evaluation of bone marrow requires
      knowledge of the morphology of bone marrow cell types, the proportion of these
      cell types normally present, and the ability to evaluate overall cellularity of
      bone marrow. Accurate interpretation of bone marrow cytologic findings depends on
      evaluation of a current complete blood cell count. These components are the
      pillars of getting the most useful information in the diagnosis of hematologic
      disorders.

PMID- 27720280
TI  - Preanalytical Considerations for Joint Fluid Evaluation.
AB  - Synovial fluid analysis is a key component of the minimum database needed to
      diagnose and manage primary and secondary articular joint disorders.
      Unfortunately, preanalytical variables can drastically alter samples submitted
      for evaluation to veterinary laboratories and it is considered the stage at which
      most laboratory error occurs. This article addresses common sources of
      preanalytical variability and error that are seen in veterinary medicine. With
      consistent quality control and reporting of specimens, downstream clinical
      decision making and management of patients can be accelerated and improved.

PMID- 27720278
TI  - Histopathologic Validation of Grayscale Carotid Plaque Characteristics Related to
      Plaque Vulnerability.
AB  - Inflammation and angiogenesis play major roles in carotid plaque vulnerability.
      The purpose of this study was to determine whether gray-scale features of carotid
      plaques are associated with histologic markers for inflammation. Thirty-eight
      individuals completed a dedicated research carotid ultrasound exam before carotid
      endarterectomy. Gray-scale analysis was performed on plaque images to measure
      plaque echogenicity (gray-scale median [GSM] pixel brightness), plaque area,
      presence of discrete white areas (DWAs) and the percent of black area near the
      lumen on any one component of the plaque. Plaques with higher ultrasound GSM had
      greater percent calcification (p = 0.013) on histopathology. Presence of an
      ultrasound DWA was associated with more plaque hemosiderin (p = 0.0005) and
      inflammation (p = 0.019) on histopathology examination. The percent of plaque
      black area in any one component was associated with a higher score for
      macroscopic ulceration (p = 0.028). Ultrasound plaque characteristics (GSM, DWAs
      and black areas) represent histopathologic markers associated with plaque
      vulnerability. ClinicalTrials.gov identifier: NCT02476396.

PMID- 27720281
TI  - The predictive value of dendritic cells in early squamous cell carcinoma of the
      tongue.
AB  - OBJECTIVES: The aim of this study was to evaluate the relationship between
      dendritic cell density in early squamous cell carcinoma (SCC) of the tongue and
      patients' clinical outcome. METHODS: Representative samples of low-risk SCC of
      the tongue (T1-2,N0,M0) from a homogeneous group of 18 patients following local
      complete excision and elective selective neck dissection, were immunostained with
      antibodies against S100 and CD1a. Dendritic cell density was analyzed by outcome.
      RESULTS: Mean dendritic cell densities were 17 cells/HPF for tumoral S100 and
      CD1a counts, and 10 cells/HPF for peritumoral S100 and CD1a counts. Better
      disease-free survival was associated with low peritumoral S100- and CD1a-
      positive cell counts (p=0.006 and p=0.004, respectively), and with low tumoral
      S100- and CD1a- positive cell counts (p=0.037 and p=0.04, respectively).
      Lymphocytic response was decreased in tumors with high dendritic cell density
      (p=NS). There was no association of dendritic cell density with patient age,
      tumor size and depth of invasion. CONCLUSIONS: These results may suggest an
      association between dendritic cell accumulation and functional immunologic
      impairment.

PMID- 27720283
TI  - ["Inequalities in the management of women with previous caesarean delivery in
      France"].

PMID- 27720282
TI  - [Clitoral reconstruction after female genital mutilation at CHU Yalgado of
      Ouagadougou, Burkina Faso. About 68 patients operated].
AB  - OBJECTIVE: The objective of this survey was to assess the results of a new
      clitoral transposition technique in the obstetrics and gynecology department of
      CHUYO. MATERIALS AND METHOD: A cohort of 68 women victims of genital mutilation
      has received clitoral reconstruction by a new technique of transposition of the
      clitoris. They were operated and followed for 12 months in CHUYO gynecology ward
      in Ouagadougou. We evaluated the management of pain, anatomical aspect,
      functional and occurrence of complications. RESULTS: Anatomically have no new
      increase was within a neoclitoris, and a very satisfactory ratio of 100 % of
      women with clitoral massif visible in the 12th month assessment. Functionally,
      before clitoral reconstruction half of the women had mild pain or discomfort
      during sexual intercourse. However, clitoral reconstruction after the 6th month
      and 12th month this pain or mild discomfort were 3.18 % and 0 % respectively. In
      addition, we noted a sensitive neoclitoris in all women, after one year. Very few
      postoperative complications were observed in this series compared to previous
      series. CONCLUSION: These results are of interest in this new clitoral
      transposition technique in favor of women victims of genital mutilation.

PMID- 27720284
TI  - [Disseminated cryptococcosis revealed by a spontaneous bacterial peritonitis].

PMID- 27720285
TI  - Reply to Raimondi et al.

PMID- 27720287
TI  - Utility of Computed Tomography and Ultrasound in Elbow Fracture.

PMID- 27720286
TI  - Repeated Potassium Testing in Hemolyzed Specimens Collected in the Emergency
      Department: More Pros Than Cons.

PMID- 27720289
TI  - New Mandated Centers for Medicare and Medicaid Services Requirements for Sepsis
      Reporting: Caution from the Field.
AB  - BACKGROUND: The release of the Center for Medicare and Medicaid Service's (CMS)
      latest quality measure, Severe Sepsis/Septic Shock Early Management Bundle (SEP
      1), has intensified the long-standing debate over optimal care for severe sepsis
      and septic shock. Although the last decade of research has demonstrated the
      importance of comprehensive bundled care in conjunction with compliance
      mechanisms to reduce patient mortality, it is not clear that SEP-1 achieves this
      aim. The heterogeneous and often cryptic presentation of severe sepsis and septic
      shock, along with the multifaceted criteria for the definition of this clinical
      syndrome, pose a particular challenge for fitting requirements to this disease,
      and implementation could have unintended consequences. OBJECTIVE: Following a
      simulated reporting exercise, in which 50 charts underwent expert review, we
      aimed to detail the challenges of, and offer suggestions on how to rethink,
      measuring performance in severe sepsis and septic shock care. DISCUSSION: There
      were several challenges associated with the design and implementation of this
      measure. The ambiguous definition of severe sepsis and septic shock, prescriptive
      fluid volume requirements, rigid reassessment, and complex abstraction logic all
      raise significant concern. CONCLUSIONS: Although SEP-1 represents an important
      first step in requiring hospitals to improve outcomes for patients with severe
      sepsis and septic shock, the current approach must be revisited. The volume and
      complexity of the currently required SEP-1 reporting elements deserve serious
      consideration and revision before they are used as measures of accountability and
      tied to reimbursement.

PMID- 27720288
TI  - Variation in the Intensity of Care for Patients with Uncomplicated Renal Colic
      Presenting to U.S. Emergency Departments.
AB  - BACKGROUND: Renal colic results in > 1 million ED visits per year, yet there
      exists a gap in understanding how the majority of these visits, namely
      uncomplicated cases, are managed. OBJECTIVE: We assessed patient- and hospital
      level variation for emergency department (ED) management of uncomplicated kidney
      stones. METHODS: We identified ED visits from non-elderly adults (aged 19-79
      years) with a primary diagnosis indicating renal stone or colic from the 2011
      Nationwide Emergency Department Sample. Patients with additional diagnostic codes
      indicating infection, sepsis, and abdominal aortic aneurysm were excluded. We
      used sample-weighted logistic regression to determine the association between
      hospital admission and having a urologic procedure with patient and hospital
      characteristics. RESULTS: Of the 1,061,462 ED visits for uncomplicated kidney
      stones in 2011, 8.0% of visits resulted in admission and 6.3% resulted in an
      inpatient urologic procedure. Uninsured patients compared to Medicaid insured
      patients were less likely to be admitted or have an inpatient urologic procedure
      (odds ratio [OR] = 0.72; 95% confidence interval [CI] 0.65-0.81 and OR = 0.80;
      95% CI 0.72-0.87, respectively). Private- and Medicare-insured patients compared
      to Medicaid-insured patients were more likely to have an inpatient urologic
      procedure (OR = 1.20; 95% CI 1.11-1.30 and OR = 1.14; 95% CI 1.04-1.25,
      respectively). CONCLUSIONS: For patients with uncomplicated renal colic, there is
      variation in the management associated with nonclinical factors, namely
      insurance. No consensus guidelines exist yet to address when to admit or utilize
      inpatient urologic procedures.

PMID- 27720290
TI  - Prognosis of Prolonged Intensive Care Unit Stay After Aortic Valve Replacement
      for Severe Aortic Stenosis in Octogenarians.
AB  - OBJECTIVES: Octogenarians considered for cardiac surgery encounter more
      complications than other patients. Postoperative complications raise the question
      of continuation of high-cost care for patients with limited life expectancy.
      Duration of hospitalization in intensive care after cardiac surgery may differ
      between octogenarians and other patients. The objectives were evaluating the
      mortality rate of octogenarians experiencing prolonged hospitalization in
      intensive care and defining the best cut-off for prolonged intensive care unit
      length of stay. DESIGN: A single-center observational study. SETTING: A
      postoperative surgical intensive care unit in a tertiary teaching hospital in
      Paris, France. PARTICIPANTS: All consecutive patients older than 80 years
      considered for aortic valve replacement for aortic stenosis were included.
      MEASUREMENTS AND MAIN RESULTS: Mortality rate was determined among patients
      experiencing prolonged stay in intensive care with organ failure and without
      organ failure. An ROC curve determined the optimal cut-off defining prolonged
      hospitalization in intensive care according to the occurrence of postoperative
      complications. Multivariate analysis determined risk factors for early death or
      prolonged intensive care stay. The optimal cut-off defining prolonged intensive
      care unit length of stay was 4 days. Low ventricular ejection fraction (odds
      ratio [OR] = 0.95; 95% confidence interval [CI] 0.96-0.83; p = 0.0016), coronary
      disease (OR = 2.34; 95% CI 1.19-4.85; p = 0.014), and need for catecholamine (OR
      = 2.79; 95% CI 1.33-5.88; p = 0.0068) were associated with eventful postoperative
      course. There was not a hospitalization duration beyond which the prognosis
      significantly worsened. CONCLUSIONS: Prolonged length of stay in ICU without
      organ failure is not associated with increased mortality. No specific duration of
      hospitalization in intensive care was associated with increased mortality.
      Continuation of care should be discussed on an individual basis.

PMID- 27720291
TI  - Impact of Milrinone Administration in Adult Cardiac Surgery Patients: Updated
      Meta-Analysis.
AB  - OBJECTIVE: To determine the effects of milrinone on short-term mortality in
      cardiac surgery patients with focus on the presence or absence of heterogeneity
      of the effect. DESIGN: A systematic review and meta-analysis. SETTING AND
      PARTICIPANTS: Five hundred thirty-seven adult cardiac surgery patients from 12
      RCTs. INTERVENTIONS: Milrinone administration. MEASUREMENTS AND MAIN RESULTS: The
      authors conducted a systematic Medline and Pubmed search to assess the effect of
      milrinone on short-term mortality in adult cardiac surgery patients. Subanalysis
      was performed according to the timing for commencement of milrinone
      administration and the type of comparators. The primary outcome was any short
      term mortality. Overall analysis showed no difference in mortality rates in
      patients who received milrinone and patients who received comparators (odds ratio
      = 1.25, 95% CI 0.45-3.51, p = 0.67). In subanalysis for the timing to commence
      milrinone administration and the type of comparators, odds ratio for mortality
      varied from 0.19 (placebo as control drug, start of administration after
      cardiopulmonary bypass) to 2.58 (levosimendan as control drug, start of
      administration after cardiopulmonary bypass). CONCLUSIONS: Among RCTs to assess
      the effect of milrinone administration in adult cardiac surgery patients, there
      are wide variations of the odds ratios of administration of milrinone for short
      term mortality according to the comparators and the timing of administration.
      This fact may suggest that a simple pooling meta-analysis is not applicable for
      assessing the risk and benefit of milrinone administration in an adult cardiac
      surgery cohort.

PMID- 27720292
TI  - The discovery of new cytotoxic pyrazolopyridine derivatives.
AB  - A number of new 3,7-disubstituted pyrazolo[3,4-c]pyridines have been designed and
      synthesized from suitable 2-aminopyridines. The antiproliferative activity of the
      derivatives was determined against the pancreatic MIA PaCa-2 and ovarian SCOV3
      cancer cell-lines. IC50 values of the most promising analogue 46 lie in the
      submicromolar or low micromolar range. Furthermore, compound 46 shows similar
      inhibitory activities against DU145, A2058 and PC-3 cancer cells, blocks the cell
      cycle at the G0/G1 phase and induce apoptosis, as determined by the appearance of
      apoptotic nuclei.

PMID- 27720293
TI  - Synthesis and pharmacological evaluation of functionalized isoindolinones on GABA
      activated chloride currents in rat cerebellum granule cells in culture.
AB  - A focused N-substituted 3-(2-piperazin-1-yl-2-oxoethyl)-2-(pyridin-2-yl)iso
      indolin-1-ones small library was synthesized for modulation of GABA-A receptor
      function and compared to Zopiclone for the ability to increase GABA-activated
      chloride currents. All compounds were tested for their effects on GABA-activated
      chloride currents in rat cerebellar granule cells by use of the whole-cell patch
      clamp technique. Electrophysiological studies on cultured cerebellar granule
      cells revealed 3-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2-(5-nitropyridin-2
      yl)iso-indolin-1-one (Id) as a partial agonist displaying 34% increase of the
      10MUM GABA evoked peak chloride currents, antagonized by flumazenil. Moreover, a
      second group of compounds, with bulky functional groups at N-4 position of
      piperazine, have shown inverse agonist effects. The simple synthetic procedure
      and the possibility of modulating the efficacy of this class of ligands through
      additional structural modifications pave the way for further development of new
      molecules as a novel class of compounds able to interfere with benzodiazepine
      receptors.

PMID- 27720294
TI  - Structure-activity of antifungal compounds inspired by aminobisabolenes from the
      sponge Halichondria sp.
AB  - Structure-activity relationships of the antifungal aminobisabolene natural
      product, 1 isolated from Halichondria sp., and synthetic analogs were explored,
      in parallel with the antidermatophytic allylamine, Terbinafine(r), against a
      panel of pathogenic fungi: Candida spp., Cryptococcus spp. and Trichophyton
      rubrum. Interpretation of the results suggest different modes of action in
      antifungal activity for the two classes of compounds.

PMID- 27720295
TI  - Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for
      treating African sleeping sickness.
AB  - Trypanosoma brucei are protozoan parasites that cause African sleeping sickness
      in humans (also known as Human African Trypanosomiasis-HAT). Without treatment,
      T. brucei infections are fatal. There is an urgent need for new therapeutic
      strategies as current drugs are toxic, have complex treatment regimens, and are
      becoming less effective owing to rising antibiotic resistance in parasites. We
      hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a
      viable anti-trypanosomal strategy as parasites rely on these stress response
      elements for their development and survival. We recently discovered several
      hundred inhibitors of the prototypical HSP60/10 chaperonin system from
      Escherichia coli, termed GroEL/ES. One of the most potent GroEL/ES inhibitors we
      discovered was compound 1. While examining the PubChem database, we found that a
      related analog, 2e-p, exhibited cytotoxicity to Leishmania major promastigotes,
      which are trypanosomatids highly related to Trypanosoma brucei. Through initial
      counter-screening, we found that compounds 1 and 2e-p were also cytotoxic to
      Trypanosoma brucei parasites (EC50=7.9 and 3.1MUM, respectively). These
      encouraging initial results prompted us to develop a library of inhibitor analogs
      and examine their anti-parasitic potential in vitro. Of the 49 new chaperonin
      inhibitors developed, 39% exhibit greater cytotoxicity to T. brucei parasites
      than parent compound 1. While many analogs exhibit moderate cytotoxicity to human
      liver and kidney cells, we identified molecular substructures to pursue for
      further medicinal chemistry optimization to increase the therapeutic windows of
      this novel class of chaperonin-targeting anti-parasitic candidates. An intriguing
      finding from this study is that suramin, the first-line drug for treating early
      stage T. brucei infections, is also a potent inhibitor of GroEL/ES and HSP60/10
      chaperonin systems.

PMID- 27720296
TI  - Synthesis of novel ethyl 2,4-disubstituted 8
      (trifluoromethyl)pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-9-carboxylate
      derivatives as promising anticancer agents.
AB  - A series of novel pyrido[2',3':3,4] pyrazolo[1,5-a]pyrimidine derivatives 6-9
      were prepared in single step starting from 3-amino-6-(trifluoromethyl)-1H
      pyrazolo[3,4-b]pyridine-5-carboxylate 5 on reaction with symmetrical and
      unsymmetrical aliphatic and aromatic 1,3-diketones/alpha,beta unsaturated
      ketones/alpha,beta unsaturated keto ethers under conventional method. All the
      final compounds 6a-c, 8a-b and 9a-l were screened for anticancer activity against
      five human cancer cell lines such as PC-3 (CRL-1435), MDA-MB-231 (HTB-26), Hep G2
      (HB-8065), HeLa (CCL-2) and normal HUVEC (CRL-1730). Compounds 8a, 9f and 9k
      which showed promising anticancer activity have been identified. Further, the
      promising compounds (8a and 9f) were able to inhibit the human topoisomerase I
      (TopI) activity similar to that of camptothecin.

PMID- 27720297
TI  - Marek's disease herpesvirus vaccines integrate into chicken host chromosomes yet
      lack a virus-host phenotype associated with oncogenic transformation.
AB  - Marek's disease (MD) is a lymphotropic and oncogenic disease of chickens that can
      lead to death in susceptible and unvaccinated host birds. The causative pathogen,
      MD virus (MDV), a highly oncogenic alphaherpesvirus, integrates into host genome
      near the telomeres. MD occurrence is controlled across the globe by biosecurity,
      selective breeding for enhanced MD genetic resistance, and widespread vaccination
      of flocks using attenuated serotype 1 MDV or other serotypes. Despite over 40
      years of usage, the specific mechanism(s) of MD vaccine-related immunity and anti
      tumor effects are not known. Here we investigated the cytogenetic interactions of
      commonly used MD vaccine strains of all three serotypes (HVT, SB-1, and Rispens)
      with the host to determine if all were equally capable of host genome
      integration. We also studied the dynamic profiles of chromosomal association and
      integration of the three vaccine strains, a first for MD vaccine research. Our
      cytogenetic data provide evidence that all three MD vaccine strains tested
      integrate in the chicken host genome as early as 1 day after vaccination similar
      to oncogenic strains. However, a specific, transformation-associated virus-host
      phenotype observed for oncogenic viruses is not established. Our results
      collectively provide an updated model of MD vaccine-host genome interaction and
      an improved understanding of the possible mechanisms of vaccinal immunity.
      Physical integration of the oncogenic MDV genome into host chromosomes along with
      cessation of viral replication appears to have joint signification in MDV's
      ability to induce oncogenic transformation. Whereas for MD vaccine serotypes, a
      sustained viral replication stage and lack of the chromosome-integrated only
      stage were shared traits during early infection.

PMID- 27720298
TI  - Rationale for selection of developmentally regulated genes as vaccine candidates
      against Leishmania infantum infection.

PMID- 27720300
TI  - Laparoscopic surgery during pregnancy. A survey among European Obstetricians and
      Gynecologists.

PMID- 27720299
TI  - Inadequate reporting of enrolled patient and study site characteristics, and
      inter-study site differences in randomized controlled trials: A systematic review
      in six leading medicine journals.

PMID- 27720301
TI  - Commentary on 'Long-term Results of Totally Laparoscopic Aorto-bi-femoral
      Bypass'.

PMID- 27720302
TI  - Contribution of the Pubofemoral Ligament to Hip Stability: A Biomechanical Study.
AB  - PURPOSE: To determine the isolated function of the pubofemoral ligament of the
      hip capsule and its contribution to hip stability in external/internal rotational
      motion during flexion greater than 30 degrees  and abduction. METHODS: Thirteen
      hips from 7 fresh-frozen pelvis-to-toe cadavers were skeletonized from the lumbar
      spine to the distal femur with the capsular ligaments intact. Computed
      tomographic imaging was performed to ensure no occult pathological state existed,
      and assess bony anatomy. Specimens were placed on a surgical table in supine
      position with lower extremities resting on a custom-designed polyvinylchloride
      frame. Hip internal and external rotation was measured with the hip placed into a
      combination of the following motions: 30 degrees , 60 degrees , 110 degrees  hip
      flexion and 0 degrees , 20 degrees , 40 degrees  abduction. Testing positions
      were randomized. The pubofemoral ligament was released and measurements were
      repeated, followed by releasing the ligamentum teres. RESULTS: Analysis of the
      2,106 measurements recorded demonstrates the pubofemoral ligament as a main
      controller of hip internal rotation during hip flexion beyond 30 degrees  and
      abduction. Hip internal rotation was increased up to 438.9% (P < .001) when the
      pubofemoral ligament was released and 412.9% (P < .001) when both the pubofemoral
      and teres ligament were released, compared with the native state. CONCLUSIONS:
      The hypothesis of the pubofemoral ligament as one of the contributing factors of
      anterior inferior hip stability by controlling external rotation of the hip in
      flexion beyond 30 degrees  and abduction was disproved. The pubofemoral ligament
      maintains a key function in limiting internal rotation in the position of
      increasing hip flexion beyond 30 degrees  and abduction. This cadaveric study
      concludes previous attempts at understanding the anatomical and biomechanical
      function of the capsular ligaments and their role in hip stability. CLINICAL
      RELEVANCE: The present study contributes to the understanding of hip stability
      and biomechanical function of the pubofemoral ligament.

PMID- 27720304
TI  - Revision Arthroscopic Acetabular Labral Treatment: Repair or Reconstruct?
AB  - PURPOSE: To compare the outcome of labral repair versus labral reconstruction in
      patients presenting to a single surgeon for revision hip arthroscopy following
      previous labral treatment. METHODS: Patients who underwent revision labral repair
      or labral reconstruction using iliotibial band allograft, after previous labral
      debridement or repair, between 2009 and 2013 were identified. Hips that underwent
      revision labral reconstruction were further stratified into 2 graft groups
      (freeze-dried vs frozen allograft). Exclusion criteria were age <16 years,
      previous open hip surgery, or previous labral reconstruction. Failure was defined
      by subsequent intra-articular hip surgery. RESULTS: 113 hips (15 repair, 98
      reconstruction) met the inclusion criteria. Patients who underwent revision
      labral repair were younger than patients who underwent revision labral
      reconstruction (27.8 years vs 34.6 years; P = .02). Follow-up was obtained from
      14 (93%) labral repairs at an average of 4.7 years postoperation (range: 2.0-6.0
      years) and 90 (92%) labral reconstructions at an average of 2.4 years
      postoperation (range: 2.0-4.0 years). Seven of 14 (50%) labral repair hips failed
      compared with 11/90 (12%) labral reconstruction hips (P < .01). Six of 61 (10%)
      frozen allografts failed compared with 5/29 (17%) freeze-dried allografts (P =
      .32). Patients who underwent revision labral repair were 4.1 (95% confidence
      interval 1.9, 8.8) times more likely to fail than patients who underwent revision
      labral reconstruction. CONCLUSIONS: Patients who underwent revision labral repair
      following previous repair or debridement were 2.6 times more likely to fail than
      patients who underwent revision labral reconstruction, controlling for calendar
      time. In addition, revision labral reconstruction with frozen allograft had lower
      propensity of failure than freeze-dried allograft. However, there was no
      statistically significant difference in patient-reported outcome scores between
      the 2 groups. Based on these results, complete labral reconstruction with longer,
      nonsegmental graft led to a lower failure rate in this study population and can
      be considered for treatment of patients presenting for revision labral treatment.
      LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 27720303
TI  - Does the Hip Capsule Remain Closed After Hip Arthroscopy With Routine Capsular
      Closure for Femoroacetabular Impingement? A Magnetic Resonance Imaging Analysis
      in Symptomatic Postoperative Patients.
AB  - PURPOSE: The purpose of this study was to examine the hip capsule in a subset of
      symptomatic patients who underwent capsular closure during hip arthroscopy.
      METHODS: All patients undergoing primary hip arthroscopy for femoroacetabular
      impingement (FAI) with routine capsular closure between January 1, 2012, and
      December 31, 2015, were eligible. Only patients with unilateral surgery and a
      postoperative magnetic resonance imaging (MRI; ordered for persistent symptoms)
      were included. Four independent reviewers evaluated each hip capsule for
      thickness and the absence or presence of defects. RESULTS: During the study,
      1,463 patients had hip arthroscopy for FAI with routine capsular closure, and 53
      (3.6%) underwent a postoperative MRI. Fourteen of the 53 were excluded owing to
      revision status or additional procedures. The final study population included 39
      patients (23 female patients and 16 male patients), with an average patient age
      of 31.7 +/- 11.4 years and an average body mass index of 23.3 +/- 2.9. There were
      3 (7.5%) capsular defects, and the intraclass correlation coefficient (ICC) was
      0.82. The operative hip capsule was significantly thicker in the zone of
      capsulotomy, and subsequent repair as compared with the unaffected, contralateral
      hip capsule (5.0 +/- 1.2 mm vs 4.6 +/- 1.4 mm; P = .02), ICC 0.83. Additionally,
      males had thicker hip capsules as compared with their female counterparts, on the
      operative side (5.4 +/- 1.1 mm vs 4.5 +/- 1.2 mm; P = .02) and the nonoperative
      side (4.8 +/- 1.6 mm vs 4.1 +/- 0.9 mm; P = .08). CONCLUSIONS: In a subset of
      symptomatic patients after hip arthroscopy for FAI, the majority (92.5%) of the
      repaired hip capsules remained closed at greater than 1 year of follow-up. The
      hip capsule adjacent to the capsulotomy and subsequent repair is thickened
      compared with the same location on the contralateral, nonoperative hip. Aside
      from gender, patient-related and FAI-related factors do not correlate with
      capsular thickness nor do they seem to correlate with the propensity to develop a
      capsular defect. LEVEL OF EVIDENCE: Level IV, prognostic case series.

PMID- 27720305
TI  - Histopathological findings of pigmented lesion and recovery of natural skin
      colour in a patient with polymyxin B-associated diffuse hyperpigmentation.

PMID- 27720307
TI  - Self-organization in development, regeneration and organoids.
AB  - Self-organization of cells is a fundamental design principle in biology, yet the
      inherent non-linearity of self-organizing systems often poses significant
      challenges in deciphering the underlying mechanisms. Here, we discuss recent
      progress in this respect, focusing on examples from development, regeneration and
      organoid differentiation. Together, these three paradigms emphasize the active
      material properties of tissues that result from the functional coupling between
      individual cells as active units. Further, we discuss the challenge of obtaining
      reproducible outcomes on the basis of self-organizing systems, which development
      and regeneration, but not the current organoid culture protocols, achieve.

PMID- 27720306
TI  - Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1
      phosphate (S1P) in acute lung injury: Role of S1P lyase.
AB  - Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive
      sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine
      kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid
      phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are
      attributed to its unique inside-out (extracellular) signaling via G-protein
      coupled S1P1-5 receptors, and intracellular receptor independent signaling.
      Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2
      activity, regulates histone acetylation, and transcription of pro-inflammatory
      genes. Here, we present data on the role of S1P lyase mediated S1P signaling in
      regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase
      expression or activity attenuated LPS-induced histone acetylation and secretion
      of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Delta2
      hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced
      in the cytoplasmic compartment of the endothelial cell seems to modulate histone
      acetylation pattern, which is different from the nuclear SphK2/S1P signaling and
      inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain
      fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis
      induced lung inflammation. Trapping fatty aldehydes and other short chain
      aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid
      peroxidation, respectively by cell permeable agents such as phloretin or other
      aldehyde trapping agents may be useful in treating sepsis-induced lung
      inflammation via modulation of histone acetylation. .

PMID- 27720309
TI  - Role of uteroplacental and fetal Doppler in identifying fetal growth restriction
      at term.
AB  - Identification of the fetus at risk of adverse outcome at term is a challenge to
      both clinicians and researchers alike. Despite the fact that fetal growth
      restriction (FGR) is a known risk factor for stillbirth, at least two thirds of
      the stillbirth cases at term are not small for gestational age (SGA) - a commonly
      used proxy for FGR. However, the majority of SGA fetuses are constitutionally
      small babies and do not suffer from adverse perinatal outcome. The
      cerebroplacental ratio (CPR) is emerging as a marker of failure to reach growth
      potential at term. CPR is an independent predictor of intrapartum fetal distress,
      admission to the neonatal unit at term, stillbirth, perinatal death and neonatal
      morbidity. Raised uterine artery Doppler resistance in the third trimester is
      independently associated with significantly lower birthweight and CPR. The
      combination of the estimated fetal weight, CPR and uterine Doppler in the third
      trimester can identify the majority of fetuses at risk of stillbirth.

PMID- 27720308
TI  - Re-establishment of nucleosome occupancy during double-strand break repair in
      budding yeast.
AB  - Homologous recombination (HR) is an evolutionarily conserved pathway in
      eukaryotes that repairs a double-strand break (DSB) by copying homologous
      sequences from a sister chromatid, a homologous chromosome or an ectopic
      location. Recombination is challenged by the packaging of DNA into nucleosomes,
      which may impair the process at many steps, from resection of the DSB ends to the
      re-establishement of nucleosomes after repair. However, nucleosome dynamics
      during DSB repair have not been well described, primarily because of a lack of
      well-ordered nucleosomes around a DSB. We designed a system in budding yeast
      Saccharomyces cerevisiae to monitor nucleosome dynamics during repair of an HO
      endonuclease-induced DSB. Nucleosome occupancy around the break is lost following
      DSB formation, by 5'-3' resection of the DSB end. Soon after repair is complete,
      nucleosome occupancy is partially restored in a repair-dependent but cell cycle
      independent manner. Full re-establishment of nucleosome protection back to the
      level prior to DSB induction is achieved when the cell cycle resumes following
      repair. These findings may have implications to the mechanisms by which cells
      sense the completion of repair.

PMID- 27720310
TI  - Sensitivity of clinically relevant dosimetric parameters to contouring
      uncertainty in postimplant dosimetry of low-dose-rate prostate permanent seed
      brachytherapy.
AB  - PURPOSE: There is strong evidence relating postimplant dosimetry for low-dose
      rate prostate seed brachytherapy to local control rates. The delineation of the
      prostate on CT images, however, represents a challenge due to the lack of soft
      tissue contrast to identify the prostate borders. This study aims at quantifying
      the sensitivity of prostate V100 and D90 to contouring uncertainty as clinically
      relevant parameters for evaluation of target coverage in postimplant dosimetry.
      METHODS AND MATERIALS: CT images, postoperative plans, and contours of a cohort
      of patients (n = 43; low risk = 55.8%, intermediate risk = 39.5%, high risk =
      4.7%), who had received prostate seed brachytherapy, were imported into MIM
      Symphony treatment planning system. The prostate contours in postimplant CT
      images were expanded or contracted uniformly in extents of +/-1.00 mm, +/-2.00
      mm, +/-3.00 mm, +/-4.00 mm, and +/-5.00 mm. The values for V100 and D90 were
      extracted from dose-volume histograms for each contour and compared. RESULTS:
      Significant changes were observed in the values of D90 and V100 as well as the
      number of inacceptable plans for expansion or contraction of only few
      millimeters. Evaluation of a plan coverage based on D90 was found to be less
      sensitive to systematic contouring errors compared with V100. Number of plans
      incorrectly identified for lack or adequacy of coverage is lower using D90
      compared with V100 for the same margin of error. CONCLUSIONS: Evaluation of a
      plan coverage based on V100 is too sensitive to systematic contouring errors of
      prostate. D90 increases the accuracy of CT-based postimplant quality assurance in
      identifying plans with insufficient coverage compared with V100.

PMID- 27720311
TI  - Predictive factors of rectal toxicity after permanent iodine-125 seed
      implantation: Prospective cohort study in 2339 patients.
AB  - PURPOSE: To evaluate the incidence and the associated factors of rectal toxicity
      in patients with prostate cancer undergoing permanent seed implantation (PI) with
      or without external beam radiation therapy (EBRT) in a nationwide prospective
      cohort study in Japan (J-POPS) during the first 2 years. METHODS AND MATERIALS: A
      total of 2,339 subjects were available for the analyses. Rectal toxicity was
      evaluated using the National Cancer Institute Common Terminology Criteria for
      Adverse Events version 3.0. RESULTS: The 3-year cumulative incidence for grade
      >=2 rectal toxicity was 2.88%, 1.76%, and 6.53% in all subjects, PI group and
      EBRT combination therapy group, respectively. On multivariate analysis, among all
      subjects, grade >=2 rectal toxicity was associated with rectal volumes receiving
      100% of the prescribed dose (R100; p < 0.0001) and EBRT combination therapy (p =
      0.0066). R100 in the PI group (p = 0.0254), and R100 (p = 0.0011) and interactive
      planning (p = 0.0267) in the EBRT combination therapy group were also associated
      with grade >=2 toxicity. The 3-year cumulative incidence of grade >=2 rectal
      toxicity was 3.80% and 1.37% for R100 >= 1 mL and R100 < 1 mL, respectively, in
      the PI group (p = 0.0068), and 14.09% and 5.52% for R100 >= 1 mL and R100 < 1 mL,
      respectively, in the EBRT combination therapy group (p = 0.0070). CONCLUSIONS:
      Rectal toxicity was relatively rare in this study compared with previous reports.
      For Japanese prostate cancer patients, R100 < 1 mL in both PI and EBRT
      combination therapy groups and interactive planning in EBRT combination therapy
      group may be effective in decreasing the incidence of rectal toxicity.

PMID- 27720312
TI  - The surgical management of patients with clinical stage T4 bladder cancer: A
      single institution experience.
AB  - INTRODUCTION: Patients with clinical T4 (cT4) bladder cancer (BCa) infrequently
      undergo radical cystectomy (RC). We investigated the reliability of preoperative
      clinical staging, perioperative and survival outcomes in patients treated with RC
      due to cT4a-b BCa disease at a single tertiary care institution. METHODS: The
      study relied on 917 BCa patients treated with RC and pelvic lymph node dissection
      (PLND) at a single institution between January 1995 and December 2012. We
      compared the accuracy of the clinical assessment with final pathology results.
      Moreover, we evaluated perioperative outcomes, complication rates and survival
      after surgery. RESULTS: The median follow-up was 62 months. Overall, 74 (8.1%)
      patients presented cT4 stage at preoperative evaluation. Conversely, a
      pathological T4 disease was confirmed only in 68.9% patients staged initially as
      cT4. No differences were recorded in complications, 30 days readmission or 30
      days death rates between cT1-T3 vs. cT4a vs. cT4b (p > 0.1). At multivariable Cox
      regression analyses predicting cancer specific mortality, clinical T4 stage vs.
      clinical T1-2, clinical T3 stage vs. clinical T1-2 and age were predictors of
      worst survival after RC (all p < 0.04). CONCLUSIONS: We recorded poor concordance
      between preoperative imaging and pathology in cT4 patients. No differences in
      major perioperative outcomes and acceptable survival expectancies were reported
      in patients treated for cT4 disease.

PMID- 27720313
TI  - [Surgical complications of renal transplantation].
AB  - OBJECTIVE: To report the nature, incidence, diagnosis and treatment options of
      surgical complications after renal transplantation. MATERIAL AND METHODS:
      Relevant publications were identified through Medline
      (http://www.ncbi.nlm.nih.gov/) and Embase (http://www.embase.com/) database from
      1960 to 2016 using the following keywords "fistula; lymphocele; stricture;
      thrombosis", in association with "renal transplantation" in Title/Abstract field.
      Articles were selected according to methods, language of publication and
      relevance. A total of 7618 articles were identified including specifically 981
      for vascular complications, 1016 for urologic complications and 239 for
      lymphocele; after careful selection 190 publications were eligible for our
      review. RESULTS: Surgical complications occur in 1 to 30% of renal
      transplantations while being incompletely reported without consensual management.
      Angioplasty techniques led to a significant improvement of short- and long-term
      vascular complications outcome. Risk factors for transplant thrombosis are a
      right allotransplant, multiple renal arteries or vasculopathy in the donor,
      diabetes, arterial disease or thrombophilia in the recipient and hemodynamic
      changes during procedure. Urinary complications and lymphocele significantly
      impair overall outcome and recipients quality of life with no demonstrated impact
      on allotransplant survival. Immediate or salvage pelvi-ureterostomy is a main
      treatment option for ureteral strictures and fistula. CONCLUSION: Prevention of
      surgical complications following renal transplantation relies on careful
      allotransplant preparation and strict respect of surgical best practices.
      Increasing comorbidities in recipients as well as marginal donors are significant
      limits for the improvement of post-transplant surgical outcome.

PMID- 27720314
TI  - A pilot study of cognitive insight and structural covariance in first-episode
      psychosis.
AB  - Cognitive insight is described as a balance between one's self-reflectiveness
      (recognition and correction of dysfunctional reasoning), and self-certainty
      (overconfidence). Neuroimaging studies have linked the ventrolateral prefrontal
      cortex (VLPFC) to cognitive insight in people with psychosis. However, the
      relationship between cognitive insight and structural connectivity between the
      VLPFC and other brain areas is unknown. Here, we investigated the modulation of
      cognitive insight on structural covariance networks involving the VLPFC in a
      first-episode psychosis sample. Fifteen patients with a first-episode psychosis
      provided magnetic resonance (MR) scans and completed the Beck Cognitive Insight
      Scale (BCIS). MR scans were also available for 15 historical controls. Seed-based
      analysis of structural covariance was conducted using the Mapping Anatomical
      Correlations Across the Cerebral Cortex (MACACC) methodology, whereby Pearson
      correlation coefficients were extracted between seed regions in left and right
      VLPFC and cortical thickness across the brain. Structural covariance maps between
      groups were compared at each vertex. In first-episode subjects, we evaluated the
      modulation of BCIS scores on cortical covariance between VLPFC and every other
      vertex. Findings showed no significant group difference between first-episode
      psychosis subjects and controls in thickness covariance seeded from left or right
      VLPFC. However, in first-episode psychosis subjects, a positive association with
      self-certainty was found in networks seeded from both left and right VLPFC with
      thickness in medial frontal cortex and right pars triangularis. No significant
      associations were found for self-reflectiveness. These results suggest that self
      certainty, but not self-reflectiveness, positively modulated cortical covariance
      in a frontal network in patients with a first-episode psychosis.

PMID- 27720315
TI  - Environmental pollution and risk of psychotic disorders: A review of the science
      to date.
AB  - Environmental pollution is a global problem with diverse and substantial public
      health implications. Although many environmental (i.e., non-genetic) risk factors
      for schizophrenia and other psychotic disorders have been identified, there has
      been comparatively little research on pollution as a possible risk factor. This
      is despite the fact that gene-by-environment interactions and epigenetic
      mechanisms are now recognized as likely facets of the etiology of schizophrenia,
      and the fact that pollution could potentially mediate the association between
      urban birth/upbringing and elevated risk. We conducted a review of the literature
      to date in order to summarize and synthesize work in this area. We identified 13
      research reports and 16 review articles. Based on the extant knowledge in this
      area and what is known about the pathophysiology of schizophrenia, it is feasible
      that exposure to xenobiotic heavy metals such as lead and cadmium, constituents
      of air pollution such as particulate matter and nitrogen and sulfur oxides,
      organic solvents, and other constituents of environmental pollution could be
      component causes. Further research-from the cellular to epidemiological levels-is
      clearly needed. If causation is proven, enhancements of policy intended to reduce
      human exposure to environmental pollution could reduce the burden of
      schizophrenia and possibly other mental illnesses.

PMID- 27720316
TI  - Temporal persistence of anomalous self-experience: A 5years follow-up.
AB  - BACKGROUND: The concept of self-disorders in schizophrenia has gained substantial
      interest and it has now been established empirically that self-disorders
      aggregate in schizophrenia-spectrum disorders but not in other mental disorders
      or in healthy controls. Yet, the issue of temporal persistence has not been
      addressed. AIM: The aim of this study is to examine the temporal persistence of
      self-disorders. METHODS: 96 first admission patients were thoroughly assessed for
      psychopathology including SD at baseline and again 5years later. We created a 25
      item self-disorder scale which was used both at baseline and follow-up to assess
      self-disorders. The scale was a pre-cursor of the later published EASE-scale.
      Additionally, we examined the development of positive and negative syndromes and
      of the Global Assessment of Functioning (GAF). RESULTS: There was a high
      correlation between self-disorders at baseline and at follow-up, and the majority
      of the items in self-disorders scale showed equal proportions between baseline
      and follow-up. CONCLUSION: Self-disturbances showed a high level of persistence
      at 5-year follow-up.

PMID- 27720317
TI  - Developing professional habits of hand hygiene in intensive care settings: An
      action-research intervention.
AB  - OBJECTIVES: To explore perceptions and unconscious psychological processes
      underlying handwashing behaviours of intensive care nurses, to implement
      organisational innovations for improving hand hygiene in clinical practice.
      RESEARCH METHODOLOGY: An action-research intervention was performed in 2012 and
      2013 in the intensive care unit of a public hospital in Italy, consisting of:
      structured interviews, semantic analysis, development and validation of a
      questionnaire, team discussion, project design and implementation. Five general
      workers, 16 staff nurses and 53 nurse students participated in the various
      stages. RESULTS: Social handwashing emerged as a structured and efficient habit,
      which follows automatically the pattern "cue/behaviour/gratification" when hands
      are perceived as "dirty". The perception of "dirt" starts unconsciously the
      process of social washing also in professional settings. Professional handwashing
      is perceived as goal-directed. The main concern identified is the fact that
      washing hands requires too much time to be performed in a setting of urgency.
      These findings addressed participants to develop a professional "habit-directed"
      hand hygiene procedure, to be implemented at beginning of workshifts.
      CONCLUSIONS: Handwashing is a ritualistic behaviour driven by deep and
      unconscious patterns, and social habits affect professional practice. Creating
      professional habits of hand hygiene could be a key solution to improve compliance
      in intensive care settings.

PMID- 27720318
TI  - Heterogeneous histomorphology, yet homogeneous vascular smooth muscle cell
      dedifferentiation, characterize human aneurysm disease.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) is a frequent, potentially life
      threatening, disease that can only be treated by surgical means such as open
      surgery or endovascular repair. No alternative treatment is currently available,
      and despite expanding knowledge about the pathomechanism, clinical trials on
      medical aneurysm abrogation have led to inconclusive results. The heterogeneity
      of human AAA based on histologic examination is thereby generally neglected. In
      this study we aimed to further elucidate the role of these differences in
      aneurysm disease. METHODS: Tissue samples from AAA and popliteal artery aneurysm
      patients were examined by histomorphologic analysis, immunohistochemistry,
      Western blot, and polymerase chain reaction. The results were correlated with
      clinical data such as aneurysm diameter and laboratory results. RESULTS: The
      morphology of human AAA vessel wall probes varies tremendously based on the grade
      of inflammation. This correlates with increasing intima/media thickness and
      upregulation of the vascular endothelial growth factor cascade but not with any
      clinical parameter or the aneurysm diameter. The phenotypic switch of vascular
      smooth muscle cells occurred regardless of the inflammatory state and
      expressional changes of the transcription factors Kruppel-like factor-4 and
      transforming growth factor-beta lead to differential protein localization in
      aneurysmal compared with control arteries. These changes were in similar manner
      also observed in samples from popliteal artery aneurysms, which, however, showed
      a more homogenous phenotype. CONCLUSIONS: Heterogeneity of AAA vessel walls based
      on inflammatory morphology does not correlate with AAA diameter yet harbors
      specific implications for basic research and possible aneurysm detection.

PMID- 27720319
TI  - A multicenter experience with infected abdominal aortic endograft explantation.
AB  - OBJECTIVE: Endovascular aneurysm repair (EVAR) is widely used with excellent
      results, but its infectious complications can be devastating. In this paper, we
      report a multicenter experience with infected EVAR, symptoms, and options for
      explantation and their outcome. METHODS: We have reviewed all consecutive
      endograft explants for infection at 11 French university centers following EVAR,
      defined as index EVAR, from 1998 to 2015. Diagnosis of infected aortic endograft
      was made on the basis of clinical findings, cultures, imaging studies, and
      intraoperative findings. RESULTS: Thirty-three patients with an infected aortic
      endograft were identified. In this group, at index EVAR, six patients (18%)
      presented with a groin or psoas infection and six patients (18%) presented with a
      general infection, including catheter-related infection (n = 3), prostatitis (n =
      1), cholecystitis (n = 1), and pneumonia (n = 1). After index EVAR, eight
      patients underwent successful inferior mesenteric artery embolization for a type
      II endoleak within 6 months of index EVAR and one patient received an additional
      stent for a type Ib endoleak 1 week after index EVAR. Median time between the
      first clinical signs of infection and endograft explantation was 30 days (range,
      1 day to 2.2 years). The most common presenting characteristics were pain and
      fever in 21 patients (64%) and fever alone in 8 patients (24%). Suprarenal
      fixation was present in 20 of 33 endografts (60%). All patients underwent
      endograft explantation, with bowel resection in 12 patients (36%) presenting with
      an endograft-enteric fistula. Methods of reconstruction were graft placement in
      situ in 30 patients and extra-anatomic bypass in 3 patients. In situ conduits
      were aortic cryopreserved allografts in 23, polyester silver graft in 5, and
      autogenous femoral vein in 2. Microbiology specimens obtained from the endograft
      and the aneurysm were positive in 24 patients (74%). Gram-positive organisms were
      the most commonly found in 18 patients (55%). Early mortality (30 days or in the
      hospital) was 39% (n = 13) in relation to graft blowout (n = 3), multiple organ
      failure (n = 6), colon necrosis (n = 3), and peripheral embolism (n = 1). At 1
      year, the rates of patient survival, graft-related complications, and reinfection
      were 44%, 10%, and 5%, respectively. CONCLUSIONS: Abdominal aortic endograft
      explantation for infection is high risk and associated with graft-enteric fistula
      in one-third of the cases. Larger multicenter studies are needed to better
      understand the risk factors and to improve preventive measures at index EVAR and
      during follow-up.

PMID- 27720320
TI  - Description of a risk predictive model of 30-day postoperative mortality after
      elective abdominal aortic aneurysm repair.
AB  - OBJECTIVE: Despite vast improvement in the field of vascular surgery, elective
      abdominal aortic aneurysm (AAA) repair still leads to perioperative death.
      Patients with asymptomatic AAAs, therefore, would benefit from an individual risk
      assessment to help with decisions regarding operative intervention. The purpose
      of this study was to describe such a 30-day postoperative (POD) risk prediction
      model using American College of Surgeons National Surgical Quality Improvement
      Project (NSQIP) data. METHODS: The NSQIP database (2005-2011) was queried for
      patients undergoing elective AAA repair using open or endovascular techniques.
      Clinical variables and known predictors of mortality were included in a full
      prediction model. These variables included procedure type, patient's age,
      functional dependence and comorbidities, and surgeon's specialty. Backward
      elimination with alpha-level of 0.2 was used to construct a parsimonious model.
      Model discrimination was evaluated in equally sized risk quintiles. RESULTS: The
      overall mortality rate for 18,917 elective AAA patients was 1.7%. In this model,
      surgeon's specialty was not predictive of POD. The most significant factors
      affecting POD included open repair (odds ratio [OR], 2.712; 95% confidence
      interval [CI], 2.119-3.469; P < .001), age >70 (OR, 2.243; 95% CI, 1.695-3.033; P
      < .001), functional dependency (OR, 2.290; 95% CI, 1.442-3.637; P < .001),
      creatinine above 2.0 mg/dL (OR, 2.1; 95% CI, 1.403-3.142; P < .001) and low
      hematocrit levels (OR, 2.157; 95% CI, 1.365-3.408; P = .001).The discriminating
      ability of the NSQIP model was reasonable (C-statistic = 0.751) and corrected to
      0.736 after internal validation. The NSQIP model performed well predicting
      mortality among risk-group quintiles. CONCLUSIONS: The NSQIP risk prediction
      model is a robust vehicle to predict POD among patient undergoing elective AAA
      repair. This model can be used for risk stratification of patients undergoing
      elective AAA repair.

PMID- 27720321
TI  - Continuous alternating inhaled antibiotic therapy in CF: A single center
      retrospective analysis.
AB  - INTRODUCTION: The efficacy of inhaled antibiotics to treat chronic Pseudomonas
      aeruginosa pulmonary infection in patients with cystic fibrosis (CF) has been
      well established. Few data are available on the value of continuous alternating
      inhaled antibiotic therapy (CAIT), a strategy increasingly used in the management
      of CF. OBJECTIVE: To investigate the effect of CAIT on clinical outcome in adult
      CF patients treated at the University Hospital Leuven. METHODS: Patients with a
      documented CF diagnosis who received inhaled antibiotics between March 2010 and
      January 2015 were retrospectively evaluated. In patients receiving CAIT patient
      characteristics, recorded spirometry data and number of IV antibiotic days were
      collected retrospectively at fixed time intervals, from 6months before to one
      year after the start of the 2nd inhaled antibiotic. For patients on inhaled
      antibiotic monotherapy (IAMT), the same data were obtained at similar intervals
      during the study period. RESULTS: A total of 49 of 89 patients using chronic
      inhaled antibiotic therapy received CAIT. Patients receiving CAIT had a lower
      baseline FEV1 and were more likely to be homozygous for F508del compared to
      patients receiving IAMT. FEV1 deteriorated on average by a factor of 0.904 per
      year (95% CI: 0.851-0.960) prior to the start of CAIT. The initiation of CAIT was
      associated with an average improvement in FEV1 by a factor of 1.148 per year (95%
      CI: 1.068-1.236, p=0.0002). The analysis of specific types of antibiotics
      revealed evidence of positive effects of adding COLI to TOBI and COLI to AZLI. We
      found no effect of the initiation of CAIT on the number of IV antibiotic days
      (p=0.80). CONCLUSION: CF patients with more advanced lung disease are more likely
      to receive CAIT. In this patient group, CAIT was associated with a significant
      improvement in FEV1. Further data are warranted to identify the value of CAIT.

PMID- 27720322
TI  - RE: "Low back pain misdiagnosis or missed diagnosis: Core principles" (Monie AP,
      Fazey PJ, Singer KP. Manual Therapy 22 (2016) 68-71).

PMID- 27720323
TI  - Relationship between time to treatment and mortality among patients undergoing
      primary percutaneous coronary intervention according to Korea Acute Myocardial
      Infarction Registry.
AB  - BACKGROUND: Despite large reductions in door-to-balloon times over the period,
      several studies from regional and national data showed that annual mortality
      rates were not decreased among patients who underwent primary percutaneous
      coronary intervention (PCI). However, these studies mostly focused on door-to
      balloon time, and there was no consideration of total ischemic time in a trend of
      mortality. The aim of this study was to assess the annual trend between time to
      treatment and 1-month mortality among patients undergoing primary PCI. METHODS
      AND RESULTS: The study population consisted of 8040 patients who underwent
      primary PCI at hospitals participating in the nationwide prospective Korea Acute
      Myocardial Infarction Registry (KAMIR) between January 2008 and December 2011.
      The primary end point of this study was 1-month all-cause mortality, and time to
      treatment (door-to-balloon time, symptom-to-balloon time). One-month death
      occurred in 452 patients (5.6%) from 2008 to 2011. Additional reductions in door
      to-balloon time were not translated into parallel reductions in mortality rate
      and total ischemic time. After adjustment using clinical risk, shorter total
      ischemic time was an independent predictor of 1-month mortality [adjusted odds
      ratio (OR) 0.78, 95% confidential interval (CI) 0.62-0.99, p=0.04]. Total
      ischemic time could be reduced by using emergency medical services. CONCLUSION:
      Despite improvements in door-to-balloon time, no parallel reductions in mortality
      rate and total ischemic time were observed. Total ischemic time was associated
      with mortality. The present study suggests that additional efforts are needed to
      shorten total ischemic time including patient and pre-hospital systemic delay for
      better prognosis after primary PCI.

PMID- 27720324
TI  - Biological evaluation of tetracationic compounds based on two 1,4
      diazabicyclo[2.2.2]octane moieties connected by different linkers.
AB  - A series of 1,4-diazabicyclo[2.2.2]octane derivatives differing by linker moiety
      was evaluated for activity against several strains of both Gram-positive and Gram
      negative bacteria including drug-resistant strains, one strain of fungus and
      influenza virus A/Puerto Rico/8/34 (H1N1). All compounds exhibited high
      antibacterial activity against all bacteria except Proteus vulgaris. The minimum
      inhibitory concentrations (MICs) of compound 1c with an o-phenylenebismethyl
      linker and compound 1e with a propylene aliphatic linker were found to be low and
      were comparable or better to the reference drug ciprofloxacin for Pseudomonas
      aeruginosa and Staphylococcus aureus. Additionally, a time-kill assay was
      performed to examine the bactericidal kinetics. Compounds 1c and 1e displayed
      rapid killing effects against St. aureus and Ps. aeruginosa after 2h.
      Furthermore, compounds 1a-c with aromatic linkers and compound 1e showed the
      highest antiviral activity.

PMID- 27720325
TI  - Novel approach of fragment-based lead discovery applied to renin inhibitors.
AB  - A novel approach was conducted for fragment-based lead discovery and applied to
      renin inhibitors. The biochemical screening of a fragment library against renin
      provided the hit fragment which showed a characteristic interaction pattern with
      the target protein. The hit fragment bound only to the S1, S3, and S3SP (S3
      subpocket) sites without any interactions with the catalytic aspartate residues
      (Asp32 and Asp215 (pepsin numbering)). Prior to making chemical modifications to
      the hit fragment, we first identified its essential binding sites by utilizing
      the hit fragment's substructures. Second, we created a new and smaller scaffold,
      which better occupied the identified essential S3 and S3SP sites, by utilizing
      library synthesis with high-throughput chemistry. We then revisited the S1 site
      and efficiently explored a good building block attaching to the scaffold with
      library synthesis. In the library syntheses, the binding modes of each pivotal
      compound were determined and confirmed by X-ray crystallography and the library
      was strategically designed by structure-based computational approach not only to
      obtain a more active compound but also to obtain informative Structure Activity
      Relationship (SAR). As a result, we obtained a lead compound offering synthetic
      accessibility as well as the improved in vitro ADMET profiles. The fragments and
      compounds possessing a characteristic interaction pattern provided new structural
      insights into renin's active site and the potential to create a new generation of
      renin inhibitors. In addition, we demonstrated our FBDD strategy integrating
      highly sensitive biochemical assay, X-ray crystallography, and high-throughput
      synthesis and in silico library design aimed at fragment morphing at the initial
      stage was effective to elucidate a pocket profile and a promising lead compound.

PMID- 27720328
TI  - Multitarget-directed oxoisoaporphine derivatives: Anti-acetylcholinesterase, anti
      beta-amyloid aggregation and enhanced autophagy activity against Alzheimer's
      disease.
AB  - A series of 8- and 11-substituted oxoisoaporphine derivatives have been designed,
      synthesized, and tested for their ability to inhibit cholinesterase (ChE) in
      vitro and in vivo, and self-induced beta-amyloid (Abeta) aggregation. Their
      autophagy activity and blood-brain barrier (BBB) permeability were also assessed.
      The new derivatives exhibited high AChE inhibitory activity in vivo and in intro.
      Over half the derivatives exhibited a significant in vitro inhibitory activity
      toward the self-induced Abeta aggregation. While, treatment of SH-SY5Y cells
      overexpressing the Swedish mutant form of human beta-amyloid precursor protein
      (APPsw) with derivatives was associated with significant reduction of Abeta
      secretion levels. Moreover, one-third of the synthetic compounds were predicted
      to be able to cross the BBB to reach their targets in the central nervous system
      (CNS) according to a parallel artificial membrane permeation assay for BBB.
      Compounds 5b and 6b were chosen for assessing their autophagy activity. The
      fluorescence intensity of the BC12921 was decreased significantly after treatment
      with compounds. The result encourages us to study such compounds thoroughly and
      systematically.

PMID- 27720327
TI  - Design and synthesis of purine analogues as highly specific ligands for FcyB, a
      ubiquitous fungal nucleobase transporter.
AB  - In the course of our study on fungal purine transporters, a number of new 3
      deazapurine analogues have been rationally designed, based on the interaction of
      purine substrates with the Aspergillus nidulans FcyB carrier, and synthesized
      following an effective synthetic procedure. Certain derivatives have been found
      to specifically inhibit FcyB-mediated [3H]-adenine uptake. Molecular simulations
      have been performed, suggesting that all active compounds interact with FcyB
      through the formation of hydrogen bonds with Asn163, while the insertion of
      hydrophobic fragments at position 9 and N6 of 3-deazaadenine enhanced the
      inhibition.

PMID- 27720326
TI  - Exploration of bivalent ligands targeting putative mu opioid receptor and
      chemokine receptor CCR5 dimerization.
AB  - Modern antiretroviral therapies have provided HIV-1 infected patients longer
      lifespans and better quality of life. However, several neurological complications
      are now being seen in these patients due to HIV-1 associated injury of neurons by
      infected microglia and astrocytes. In addition, these effects can be further
      exacerbated with opiate use and abuse. One possible mechanism for such
      potentiation effects of opiates is the interaction of the mu opioid receptor
      (MOR) with the chemokine receptor CCR5 (CCR5), a known HIV-1 co-receptor, to form
      MOR-CCR5 heterodimer. In an attempt to understand this putative interaction and
      its relevance to neuroAIDS, we designed and synthesized a series of bivalent
      ligands targeting the putative CCR5-MOR heterodimer. To understand how these
      bivalent ligands may interact with the heterodimer, biological studies including
      calcium mobilization inhibition, binding affinity, HIV-1 invasion, and cell
      fusion assays were applied. In particular, HIV-1 infection assays using human
      peripheral blood mononuclear cells, macrophages, and astrocytes revealed a
      notable synergy in activity for one particular bivalent ligand. Further, a
      molecular model of the putative CCR5-MOR heterodimer was constructed, docked with
      the bivalent ligand, and molecular dynamics simulations of the complex was
      performed in a membrane-water system to help understand the biological
      observation.

PMID- 27720330
TI  - Chipping and lengthening technique for reconstruction of nonunion proximal tibial
      fracture: A case report.

PMID- 27720329
TI  - Prediction of the flooding of a mining reservoir in NW Spain.
AB  - Abandoned and flooded mines constitute underground reservoirs which must be
      managed. When pumping is stopped in a closed mine, the process of flooding should
      be anticipated in order to avoid environmentally undesirable or unexpected mine
      water discharges at the surface, particularly in populated areas. The Candin
      Fondon mining reservoir in Asturias (NW Spain) has an estimated void volume of 8
      million m3 and some urban areas are susceptible to be flooded if the water is
      freely released from the lowest mine adit/pithead. A conceptual model of this
      reservoir was undertaken and the flooding process was numerically modelled in
      order to estimate the time that the flooding would take. Additionally, the
      maximum safe height for the filling of the reservoir is discussed.

PMID- 27720331
TI  - Thermodynamic parameters for adsorption equilibrium of heavy metals and dyes from
      wastewaters: Research updated.
AB  - The standard Gibbs free energy, enthalpy and entropy change data for adsorption
      equilibrium reported in biosorption literature during January 2013-May2016 were
      listed. Since the studied biosorption systems are all near-equilibrium processes,
      the enthalpy and entropy change data evaluated by fitting temperature-dependent
      free energy data using van Hoff's equation reveal a compensation artifact.
      Additional confusion is introduced with arbitrarily chosen adsorbate
      concentration unit in bulk solution that added free energy change of mixing into
      the reported free energy and enthalpy change data. Different standard states may
      be chosen for properly describing biosorption processes; however, this makes the
      general comparison between data from different systems inappropriate. No
      conclusion should be drawn based on unjustified thermodynamic parameters reported
      in biosorption studies.

PMID- 27720332
TI  - Neuronal SOCE: Myth or Reality?
AB  - Store-operated Ca2+ entry (SOCE) is the primary Ca2+ influx pathway in non
      excitable cells. Long thought to be absent in nerve cells, neuronal SOCE is
      gaining popularity. We argue here that the evidence for SOCE in neurons remains
      contentious, mostly because SOCE imaging assays are inadequate in these cells.

PMID- 27720333
TI  - Evaluation of a refill synchronization program in two community pharmacies.
AB  - OBJECTIVES: To describe medication adherence by the proportion of days covered
      before and after enrollment in a refill synchronization program. METHODS: We
      conducted a retrospective analysis of medication adherence in 2 pharmacies
      offering a refill synchronization program. The study population consisted of
      individuals who received 2 or more medications from any of 15 predefined
      medication classes within 6 months of enrollment in the synchronization program.
      Medication adherence and refill consolidation were measured over 6 months before
      and after enrollment. Optimal adherence was defined as proportion of days covered
      >=80%. RESULTS: Among 109 patients who enrolled in the program between 2009 and
      2014, 68 were included in a pre-post analysis of medication adherence. In the
      preenrollment period, optimal adherence was observed in 85% (217/254) of the
      medications taken by the 68 patients, increasing to 93% (237/254) in the
      postenrollment period (P <0.01). In addition, the percentage maintaining optimal
      adherence to all of their medications increased significantly from 60% (n = 41)
      to 83% (n = 57; P <0.01). CONCLUSION: Among a small group of patients who
      voluntarily participated in refill synchronization programs, high levels of
      medication adherence were observed in the preenrollment period. These results
      combined with previous studies suggest that voluntary participants of these
      programs are at a low risk for nonadherence; therefore, current estimates of
      benefit from refill synchronization programs may be overestimated.

PMID- 27720335
TI  - Inattentional blindness and failures to rescue the deteriorating patient in
      critical care, emergency and perioperative settings: Four case scenarios.
AB  - BACKGROUND: Failure to identify and respond to clinical deterioration is an
      important measure of patient safety, hospital performance and quality of care.
      Although studies have identified the role of patient, system and human factors in
      failure to rescue events, the role of 'inattentional blindness' as a possible
      contributing factor has been overlooked. OBJECTIVES: To explore the nature and
      possible patient safety implications of inattentional blindness in critical care,
      emergency and perioperative nursing contexts. METHODS: Analysis of four case
      scenarios drawn from a naturalistic inquiry investigating how nurses identify and
      manage gaps (discontinuities) in care. Data were collected via in-depth
      interviews from a purposeful sample of 71 nurses, of which 20 were critical care
      nurses, 19 were emergency nurses and 16 were perioperative nurses. Case scenarios
      were identified, selected and analysed using inattentional blindness as an
      interpretive frame. RESULTS: The four case scenarios presented here suggest that
      failures to recognise and act upon patient observations suggestive of clinical
      deterioration could be explained by inattentional blindness. In all but one of
      the cases reported, vital signs were measured and recorded on a regular basis.
      However, teams of nurses and doctors failed to 'see' the early signs of clinical
      deterioration. The high-stress, high-complexity nature of the clinical settings
      in which these cases occurred coupled with high cognitive workload, noise and
      frequent interruptions create the conditions for inattentional blindness.
      CONCLUSIONS: The case scenarios considered in this report raise the possibility
      that inattentional blindness is a salient but overlooked human factor in failure
      to rescue events across the critical care spectrum. Further comparative cross
      disciplinary research is warranted to enable a better understanding of the nature
      and possible patient safety implications of inattentional blindness in critical
      care nursing contexts.

PMID- 27720334
TI  - Extracellular Vesicle Biogenesis in Helminths: More than One Route to the
      Surface?
AB  - The recent discovery that parasites release extracellular vesicles (EVs) that can
      transfer a range of effector molecules to host cells has made us re-think our
      understanding of the host-parasite interface. In this opinion article we consider
      how recent proteomics and transcriptomics studies, together with ultrastructural
      observations, suggest that more than one mechanism of EV biogenesis can occur in
      helminths. We propose that distinct EV subtypes have roles in immune modulation
      and repair of drug-induced damage, and put forward the case for targeting EV
      biogenesis pathways to achieve parasite control. In doing so we raise a number of
      outstanding research questions that must be addressed before this can happen.

PMID- 27720336
TI  - Assessment of accessory canals of the canalis sinuosus: a study of 1000 cone beam
      computed tomography examinations.
AB  - The aim of this study was to verify the presence, spatial location, and calibre
      of the accessory canals (AC) of the canalis sinuosus by cone beam computed
      tomography, and their relationship to the anterior maxilla. This retrospective
      analysis included the scans of 1000 subjects. Parameters registered were sex,
      age, number of AC, presence or absence of AC with a diameter <1.0mm, AC diameter
      (only for AC with a diameter >1.0mm), and AC location in relation to the adjacent
      teeth. Males showed a statistically higher frequency of AC than females. The
      difference in age distribution was not statistically significant. Twenty percent
      of all AC presented a diameter of a least 1.0mm. The end of the AC trajectory was
      most frequently located palatal to the anterior maxillary teeth. All
      relationships analyzed here were very weak (age vs. number of AC, age vs. AC
      diameter, number of AC vs. sex). Overall, the results of this study showed that
      AC of the canalis sinuosus are a common anatomical structure in the anterior
      maxilla, regardless of age and sex.

PMID- 27720337
TI  - A mathematical method for precisely calculating the radiographic angles of the
      cup after total hip arthroplasty.
AB  - We established a mathematical method to precisely calculate the radiographic
      anteversion (RA) and radiographic inclination (RI) angles of the acetabular cup
      based on anterior-posterior (AP) pelvic radiographs after total hip arthroplasty.
      Using Mathematica software, a mathematical model for an oblique cone was
      established to simulate how AP pelvic radiographs are obtained and to address the
      relationship between the two-dimensional and three-dimensional geometry of the
      opening circle of the cup. In this model, the vertex was the X-ray beam source,
      and the generatrix was the ellipse in radiographs projected from the opening
      circle of the acetabular cup. Using this model, we established a series of
      mathematical formulas to reveal the differences between the true RA and RI cup
      angles and the measurements results achieved using traditional methods and AP
      pelvic radiographs and to precisely calculate the RA and RI cup angles based on
      post-operative AP pelvic radiographs. Statistical analysis indicated that
      traditional methods should be used with caution if traditional measurements
      methods are used to calculate the RA and RI cup angles with AP pelvic radiograph.
      The entire calculation process could be performed by an orthopedic surgeon with
      mathematical knowledge of basic matrix and vector equations.

PMID- 27720339
TI  - Acculturation and Dental Service Use Among Asian Immigrants in the U.S.
AB  - INTRODUCTION: The objective of this study was to assess dental service
      utilization across different Asian immigrant groups and to examine the
      relationship between acculturation and dental service utilization among Asian
      immigrants in the U.S. METHODS: Data were from the 2013 and 2014 National Health
      Interview Surveys. Multiple logistic regression models were used to examine the
      association between acculturation and having a dental visit in the previous 12
      months, controlling for predisposing, enabling, and need factors. Acculturation
      was measured by length of stay in the U.S., English language proficiency, and
      U.S. citizenship. The sample was 2,948 adult Asian immigrants who were dentate.
      Data were analyzed in 2016. RESULTS: Dental service utilization varied across
      Asian immigrant groups. High English proficiency and longer length of stay were
      significantly associated with having a dental visit (p<0.05). In the final model,
      after adding enabling factors-dental insurance and family income levels-length of
      stay in the U.S. (>=5 years) remained significant, whereas English language
      proficiency was not a significant correlate of having a dental visit.
      CONCLUSIONS: Length of stay in the U.S. is a significant factor affecting dental
      service utilization among Asian immigrants.

PMID- 27720338
TI  - Built Environment and Depression in Low-Income African Americans and Whites.
AB  - INTRODUCTION: Urban environments are associated with a higher risk of adverse
      mental health outcomes; however, it is unclear which specific components of the
      urban environment drive these associations. METHODS: Using data collected in 2002
      2009 from 73,225 low-income, racially diverse individuals across the Southeastern
      U.S., analyses evaluated the cross-sectional relationship between a walkability
      index and depression. Walkability was calculated from population density, street
      connectivity, and destination count in the 1,200-meter area around participants'
      homes, and depression was measured using the Center for Epidemiologic Studies
      Depression Scale for depression symptomatology and questionnaire responses
      regarding doctor-diagnosed depression and antidepressant use. Data were analyzed
      in 2015. RESULTS: Participants living in neighborhoods with the highest
      walkability index had 6% higher odds of moderate or greater depression symptoms
      (score >=15, 95% CI=0.99, 1.14), 28% higher odds of doctor-diagnosed depression
      (95% CI=1.20, 1.36), and 16% higher odds of current antidepressant use (95%
      CI=1.08, 1.25), compared with those in the lowest walkability index. Higher
      walkability was associated with higher odds of depression symptoms in the most
      deprived neighborhoods only, whereas walkability was associated with lower odds
      of depression symptoms in the least deprived neighborhoods. CONCLUSIONS: Living
      in a more walkable neighborhood was associated with modestly higher levels of
      doctor-diagnosed depression and antidepressant use, and walkability was
      associated with greater depression symptoms in neighborhoods with higher
      deprivation. Although dense urban environments may provide opportunities for
      physical activity, they may also increase exposure to noise, air pollution, and
      social stressors that could increase levels of depression.

PMID- 27720340
TI  - A Systematic Review of Interventions to Increase Stair Use.
AB  - CONTEXT: Stair climbing is an accessible activity that can be incorporated into
      one's daily lifestyle to increase physical activity levels and provide health
      benefits. This review summarizes the effectiveness of stair interventions and
      explores key differences that may influence intervention effectiveness. EVIDENCE
      ACQUISITION: Interventions to increase stair use published from January 1990 to
      July 2015 were identified in PubMed, Sport Discus, Web of Science, Environment
      Complete, CINAHL, Trial Register of Promoting Health Interventions, Embase,
      Scopus, and PsycINFO. Eligibility criteria included original studies, published
      in peer-reviewed journals, targeting adult samples, and clearly describing
      intervention design and results. Studies were also required to measure the use of
      stairs compared with an elevator, escalator, or moving stairway at baseline and
      during at least one timepoint when the intervention was in effect. Studies were
      required to provide data to determine if the intervention resulted in significant
      changes in stair use/climbing. EVIDENCE SYNTHESIS: The search results yielded
      2,136 articles in total; 54 articles met the criteria, which resulted in a final
      sample of 67 studies included in the analyses. Interventions settings included
      public sites (75%), worksites (21%), or a combination of both (4%). For Phase 1
      results, 72% of studies reported significant improvements in stair use (n=10 of
      14) and stair climbing (n=38 of 53). CONCLUSIONS: Evidence from the review
      demonstrates support for the effectiveness of interventions to increase stair use
      and stair climbing. Although evidence supports the effectiveness of stair
      interventions in public settings, less support is provided for worksites.

PMID- 27720341
TI  - Non-Cognitive Personality Assessment and Risk of Injuries Among Army Trainees.
AB  - INTRODUCTION: Low levels of pre-accession physical fitness and activity are risk
      factors for stress fractures and other overuse musculoskeletal injuries among
      military trainees. One dimension in the Tailored Adaptive Personality Assessment
      System (TAPAS), a non-cognitive personality test given to Army applicants,
      specifically assesses propensity to engage in physical activity. This dimension
      may serve as a surrogate measure for activity or fitness. The study examines the
      associations between TAPAS dimension scores and risk of musculoskeletal injuries.
      METHODS: Fifteen TAPAS dimension scores for 15,082 U.S. Army trainees entering
      military service in 2010 were provided by the U.S. Army Research Institute for
      Social and Behavioral Sciences. During 2013-2015, the associations between TAPAS
      dimension scores (as a continuous variable) and injuries in the first 6 months of
      service were evaluated using logistic regression, with the measure of association
      being the OR. RESULTS: The TAPAS physical conditioning dimension was associated
      with musculoskeletal injuries and stress fractures among both men
      (musculoskeletal injury, OR=0.83, 95% CI=0.79, 0.86; stress fracture, OR=0.68,
      95% CI=0.57, 0.80) and women (musculoskeletal injury, OR=0.77, 95% CI=0.70, 0.85;
      stress fracture, OR=0.60, 95% CI=0.43, 082). No other dimensions were both
      significantly and consistently associated with either injury. CONCLUSIONS: The
      TAPAS physical conditioning dimension is a strong predictor of musculoskeletal
      injury and stress fracture among male and female U.S. Army trainees, and may
      serve as a pre-accession screen for self-reported physical activity.

PMID- 27720343
TI  - Electronic Cigarette Device-Related Hazards:: A Call for Immediate FDA
      Regulation.

PMID- 27720342
TI  - National and State-Specific Shingles Vaccination Among Adults Aged >=60 Years.
AB  - INTRODUCTION: Shingles (herpes zoster) causes substantial morbidity, especially
      among older adults. The shingles vaccine has been recommended for people aged
      >=60 years since 2006. This study assessed recent shingles vaccination at
      national and state levels among adults aged >=60 years. METHODS: The 2014
      Behavioral Risk Factor Surveillance System data were analyzed in 2015 to assess
      shingles vaccination coverage among adults aged >=60 years at national and state
      levels. Multivariable logistic regression and predictive marginal models
      identified factors independently associated with vaccination. RESULTS: Shingles
      vaccination coverage among adults aged >=60 years was 31.8% (95% CI=31.4%,
      32.2%). Among states, shingles vaccination coverage ranged from 17.8% (95%
      CI=15.8%, 20.0%) in Mississippi to 46.6% (95% CI=44.3%, 48.8%) in Vermont, with a
      median of 33.3%. Coverage was <25% in four states and >40% in nine states. For
      all states, coverage was significantly higher among non-Hispanic whites compared
      with non-white races except for Oregon, with coverage differences ranging from 
      33.2% in the District of Columbia to 0.9% in Oregon and a median of -16.0%.
      Characteristics independently associated with vaccination were age,
      race/ethnicity, sex, education, employment status, household income, region,
      perceived health status, health insurance status, personal healthcare provider,
      routine checkup status, and whether reporting that cost was a barrier to seeing a
      doctor. CONCLUSIONS: Coverage varied dramatically by state. State-level
      comparisons may aid in designing tailored intervention programs through sharing
      of best practices. Strategies are needed to mitigate financial barriers for both
      provider and patients, improve awareness, and increase provider recommendation of
      the vaccine.

PMID- 27720344
TI  - Long-term outcomes of hepatitis B virus-related cirrhosis treated with
      nucleos(t)ide analogs.
AB  - BACKGROUND/PURPOSE: This study aimed to evaluate the outcomes of chronic
      hepatitis B patients with cirrhosis who received long-term nucleos(t)ide analog
      therapy. METHODS: A total of 546 consecutive cirrhotic patients treated with
      entecavir (n = 359), telbivudine (n = 104), or tenofovir (n = 83) for chronic
      hepatitis B were enrolled. The incidence of hepatocellular carcinoma (HCC) and
      overall survival were evaluated. RESULTS: During a median follow-up of 39 months,
      56 (10.3%) patients developed HCC and 14 (2.6%) patients died. These outcomes
      were not associated with different antiviral use. Cox proportional hazard
      analysis showed that old age (>=60 years) [hazard ratio (HR), 1.74; p = 0.046],
      statin use (HR, 2.42; p = 0.017), low platelet count (<100,000/MUL; HR, 2.00; p =
      0.039), and variceal bleeding history (HR, 5.12; p < 0.001) were independent
      factors for HCC development. With regard to survival, Child-Pugh B/C (HR, 3.78; p
      = 0.039) and low platelet count (<105/MUL; HR, 7.82; p = 0.049) were independent
      factors. The estimated glomerular filtration rate significantly increased in
      patients receiving telbivudine (p = 0.047), but decreased in those receiving
      tenofovir (p < 0.001) at Year 2. Tenofovir use (HR, 1.98; p = 0.005) was one of
      the independent factors associated with the progression of chronic kidney disease
      stage. CONCLUSION: Long-term nucleos(t)ide analog therapy does not guarantee
      against the HCC development and mortality in chronic hepatitis B-related
      cirrhotic patients. Careful HCC surveillance is necessary in patients with old
      age, statin use, low platelet count, and variceal bleeding history.

PMID- 27720345
TI  - Transforming growth factor beta 1 increases collagen content, and stimulates
      procollagen I and tissue inhibitor of metalloproteinase-1 production of dental
      pulp cells: Role of MEK/ERK and activin receptor-like kinase-5/Smad signaling.
AB  - BACKGROUND/PURPOSE: In order to clarify the role of transforming growth factor
      beta 1 (TGF-beta1) in pulp repair/regeneration responses, we investigated the
      differential signaling pathways responsible for the effects of TGF-beta1 on
      collagen turnover, matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of
      metalloproteinase-1 (TIMP-1) production in human dental pulp cells. METHODS: Pulp
      cells were exposed to TGF-beta1 with/without pretreatment and coincubation by 1,4
      diamino-2,3-dicyano-1,4-bis(o-aminophenyl mercapto)butadiene (U0126; a mitogen
      activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK]
      inhibitor) and 4-(5-benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H- imidazol-2-yl)
      benzamide hydrate (SB431542; an activin receptor-like kinase-5/Smad signaling
      inhibitor). Sircol collagen assay was used to measure cellular collagen content.
      Culture medium procollagen I, TIMP-1, and MMP-3 levels were determined by enzyme
      linked immunosorbent assay. RESULTS: TGF-beta1 increased the collagen content,
      procollagen I, and TIMP-1 production, but slightly decreased MMP-3 production of
      pulp cells. SB431542 and U0126 prevented the TGF-beta1-induced increase of
      collagen content and TIMP-1 production of dental pulp cells. CONCLUSION: These
      results indicate that TGF-beta1 may be involved in the healing/regeneration
      processes of dental pulp in response to injury by stimulation of collagen and
      TIMP-1 production. These events are associated with activin receptor-like kinase
      5/Smad2/3 and MEK/ERK signaling.

PMID- 27720346
TI  - A fatal case of melioidosis with pancytopenia in a traveler from Indonesia.
AB  - Melioidosis, an infectious disease with high mortality, caused by Burkholderia
      pseudomallei, is endemic in southeast Asia and northern Australia. In Indonesia,
      autochthonous cases have been rarely reported, with most cases being sporadic and
      occurring in travelers. Herein, we report a fatal case of neurological
      melioidosis in a traveler from Indonesia presenting with septic shock.

PMID- 27720347
TI  - Counselling adults who experience a first seizure.
AB  - PURPOSE: A first seizure can result in significant uncertainty, fear and
      apprehension. One of the key roles of the clinician in the setting of first
      seizure is to provide accurate, timely information and counselling. METHOD: We
      review the numerous components to be considered when counselling an adult patient
      after a first seizure. RESULTS: We provide a framework and manner to provide that
      counselling. We focus on an individualized approach and provide recommendations
      and information on issues of diagnosis, etiology, prognosis, the role and
      importance of medical testing, lifestyle considerations, driving, medication and
      other key counselling considerations. CONCLUSION: Accurate, timely counselling
      can allay fears and anxieties, remove misconceptions and reduce the risk for
      injury in seizure recurrence.

PMID- 27720348
TI  - Scientific evidence and daily food for a better life: Milan, 19 June 2015.
AB  - This paper presents a report of a nutrition conference held at EXPO 2015 in
      Milan. Over the course of a day, seven speakers from four continents discussed
      the evidence and scientific processes that underpin the development of dietary
      guidelines, highlighting issues and challenges at each stage. These include the
      quality of studies associating disease outcomes with diet, specifically a
      reliance on observational studies, short duration of intervention trials, low
      statistical power and lack of follow-up. Concerns were raised over the
      oversimplification of dietary messages which promote carbohydrates in general
      without evidence of benefit, while restricting fats when meta-analyses suggests
      that different fatty acids have different effects on disease risk. The merits of
      food-based dietary guidelines and holistic dietary patterns were described,
      whereas the impact of increasing or reducing consumption of individual food
      groups or macronutrients remains unclear. The meeting ended with a restatement of
      the importance of dietary guidelines, and associated education, to improve public
      health, but a plea was made to ensure that the process of setting guidelines is
      evidence based, responsive and considers the impact of the whole diet.

PMID- 27720349
TI  - Modulators of the extracellular matrix and risk of anterior cruciate ligament
      ruptures.
AB  - OBJECTIVES: The extracellular matrix (ECM) of ligaments continuously undergoes
      remodelling in order to maintain tissue homeostasis. Several key mediators of ECM
      remodelling were chosen for investigation in the present study. It is thought
      that polymorphisms within genes encoding signalling molecules may contribute to
      inter-individual variation in the responses to mechanical loading, potentially
      altering risk of injury. DESIGN: A genetic association study was conducted on 232
      asymptomatic controls (CON) and 234 participants with surgically diagnosed
      anterior cruciate ligament (ACL) ruptures; of which 135 participants reported a
      non-contact mechanism of injury (NON subgroup). METHODS: All participants were
      genotyped for ten variants in eight genes encoding ECM remodelling proteins.
      Haplotypes and allele combinations were also inferred. RESULTS: The CASP8
      rs3834129 ins allele was significantly over-represented in the male CON group
      compared to the male NON subgroup (p=0.047, OR: 1.46, 95% CI: 1.01-2.12). In
      female participants, the IL1B rs16944 TT genotype was significantly under
      represented in the CON group compared to the NON subgroup (p=0.039, OR: 3.06, 95%
      CI: 1.09-8.64). Haplotype analysis revealed an under-representation of the CASP8
      rs3834129-rs1045485 del-G haplotype in the CON group compared to both the ACL
      group (p=0.042; haplo.score:2.03) and the NON subgroup (p=0.037;
      haplo.score:2.09). Furthermore, following a pathway-based approach, genetic
      variants involved in the cell signalling cascade were associated with ACL injury
      risk. CONCLUSIONS: The novel independent associations and allele combinations
      observed implicate the apoptosis and cell signalling cascades as potential
      contributors to ACL injury susceptibility. Furthermore, these genetic variants
      may potentially modulate ECM remodelling in response to loading and ultimately
      contribute to ligament capacity.

PMID- 27720350
TI  - Cytogenetic and immunohistochemical characterization of mammary analogue
      secretory carcinoma of salivary glands.
AB  - OBJECTIVES: Mammary analogue secretory carcinoma (MASC), initially considered a
      subset of acinic cell carcinoma (ACC), harbors an ETV6 translocation
      [t(12:15)(p13:25 q)] and is now regarded as a distinct entity. Several putative
      markers to differentiate MASC from ACC have been reported; however, the
      immunohistochemical profile is still being explored and updated. The purpose of
      this study was to further explore the cytogenetic and immunohistochemical profile
      of MASC. STUDY DESIGN: Cases were analyzed for ETV6 translocation using
      fluorescent in situ hybridization and stained for CK8, amylase, mammaglobin,
      GCDFP-15, MUC1, MUC4, STAT5a, Ki-67 (n = 37), CK7, Cam5.2, CK14, SMA, p63, S100,
      vimentin and DOG1 (n = 42). Histochemical stains for mucins were also performed
      and data collected for age, sex, and site. RESULTS: Fluorescent in situ
      hybridization showed 9 cases with ETV6 rearrangement and 2 with increased ETV6
      copies. These 11 cases showed an absence of PAS-D-resistant granules, with 10 of
      11 showing strong S100, mammaglobin, and STAT5a staining. All ACCs showed diffuse
      DOG1 staining, whereas 8/11 MASCs were negative and 3 showed only focal DOG1
      staining. CONCLUSION: DOG1 can be used in conjunction with PAS-D, S100, and
      mammaglobin to identify MASCs. Cases with increased ETV6 copies are a novel
      finding with a similar immunostaining profile and should be considered as MASCs.

PMID- 27720351
TI  - Scalp mass in a 66-year-old female.

PMID- 27720352
TI  - Pablo Perel: leading improvements in global cardiovascular health.

PMID- 27720353
TI  - Childhood obesity: changing perceptions.

PMID- 27720354
TI  - Simple protein precipitation extraction technique followed by validated
      chromatographic method for linezolid analysis in real human plasma samples to
      study its pharmacokinetics.
AB  - Fast and sensitive HPLC method was developed, optimized and validated for
      quantification of linezolid (LNZ) in human plasma using guaifenesin as an
      internal standard (IS). Analyte and IS were extracted from plasma by simple
      protein precipitation extraction technique using methanol as the precipitating
      solvent. The pretreated samples were injected in a mobile phase formed of
      acetonitrile:water:methanol (20:70:10v/v/v) in an isocratic mode at a flow rate
      of 1.5mL/min with UV detection at 251nm. Separation was done using Aglient ODS
      C18. The method showed linearity in the range of 0.75-50MUg/mL with correlation
      coefficients equals to 0.9991. Precision and accuracy were in conformity with the
      criteria normally accepted in bio-analytical method validation. The RSDs for
      intra- and inter-day assays were <3.56 and 4.63%, respectively. The intra- and
      inter-day accuracies were 94.67-98.28% and 91.25-96.18%, respectively. The mean
      absolute recoveries ranged from 92.56+/-1.78 to 95.24+/-2.84. According to
      stability results, LNZ was stable in human plasma during the storage and
      analysis. LNZ a pharmacokinetic behavior was studied by applying the proposed
      analytical method.

PMID- 27720355
TI  - Bioanalytical method development and validation: Critical concepts and
      strategies.
AB  - Bioanalysis is an essential part in drug discovery and development. Bioanalysis
      is related to the analysis of analytes (drugs, metabolites, biomarkers) in
      biological samples and it involves several steps from sample collection to sample
      analysis and data reporting. The first step is sample collection from clinical or
      preclinical studies; then sending the samples to laboratory for analysis. Second
      step is sample clean-up (sample preparation) and it is very important step in
      bioanalysis. In order to reach reliable results, a robust and stable sample
      preparation method should be applied. The role of sample preparation is to remove
      interferences from sample matrix and improve analytical system performance.
      Sample preparation is often labor intensive and time consuming. Last step is the
      sample analysis and detection. For separation and detection, liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) is method of choice in
      bioanalytical laboratories. This is due to high selectivity and high sensitivity
      of the LC-MS/MS technique. In addition the information about the analyte chemical
      structure and chemical properties is important to be known before the start of
      bioanalytical work. This review provides an overview of bioanalytical method
      development and validation. The main principles of method validation will be
      discussed. In this review GLP and regulated bioanalysis are described. Commonly
      used sample preparation techniques will be presented. In addition the role of LC
      MS/MS in modern bioanalysis will be discussed. In the present review we have our
      focus on bioanalysis of small molecules.

PMID- 27720356
TI  - Relationships Between Demographic, Clinical, and Health Care Provider Social
      Support Factors and Internalized Stigma in People Living With HIV.
AB  - Internalized HIV stigma (IHS) threatens people living with HIV (PLWH) and the
      public. Our purpose was to identify relationships between PLWH perceptions of IHS
      and demographic, clinical, overall health, health-related quality of life, and
      perceived health care provider (HCP) social support. Using survey data from PLWH
      (n = 292) in an urban HIV clinic, we first examined the reliability and validity
      of an existing IHS measure. Exploratory factor analysis revealed that the IHS
      score was composed of three factors: (a) Perception of Negative Societal Beliefs,
      (b) Fear of Disclosure, and (c) Perception of Negative HCP Beliefs, which were
      used as dependent variables in the multivariate analysis. In multivariate
      regression models, gender, education, quality of life, Getting Needed Care, and
      Trust in HCP were significantly related to at least one IHS factor. Our findings
      advance the measurement of IHS and provide a foundation for intervention
      development to reduce IHS in care settings.

PMID- 27720357
TI  - A Medical Care Missed Opportunity: Preexposure Prophylaxis and Young Black Men
      Who Have Sex With Men.
AB  - PURPOSE: HIV disproportionately impacts young black men who have sex with men
      (YBMSM). Preexposure prophylaxis (PrEP) is an effective strategy that can avert
      new HIV infections in YBMSM. Barriers exist for YBMSM to access PrEP. METHODS: We
      sought to determine factors associated with awareness of and willingness to take
      PrEP in a sample of YBMSM. RESULTS: Only 8% were currently on PrEP despite many
      (66%) reporting condomless anal sex, a recent provider visit (54%), disclosing
      their sexual orientation to their regular medical provider (62%), or a
      willingness to take PrEP (62%). In bivariate analysis, increased number of
      lifetime partners, current PrEP use, and disclosure of sexual orientation to a
      doctor were associated with awareness of PrEP, while condomless anal sex and
      higher perceived risk was associated with willingness to take PrEP. Sex with
      females was associated with lower willingness. CONCLUSIONS: Providers may be
      missing key opportunities to educate YBMSM about PrEP and incorporate PrEP into
      comprehensive sexual health care.

PMID- 27720359
TI  - Comparison the effects of two types of therapeutic exercises Frenkele vs. Swiss
      ball on the clinical balance measures in patients with type II diabetic
      neuropathy.
AB  - BACKGROUND: The number of diabetic patients is increasing in the world.
      Peripheral neuropathy is the most important problem of diabetes. Neuropathy
      eventually leads to balance impairment which is the main cause of falling down in
      these patients However, not sufficient evidences available to compare different
      protocols for improving balance in diabetic patients. OBJECTIVE: This study aimed
      to compare the effects of two therapeutic exercises on clinical balance measures
      in patients with type II diabetic peripheral neuropathy. METHODS: The study was
      performed on 60 patients with diabetes categorized randomly into three groups: an
      intervention group (N=20) that received ball training exercise, another
      intervention group (N=20) that received Frenkel exercise and a control group
      (N=20) that received no interventions. Exercise training session was performed
      for 3 weeks. Then, clinical balance measures were computed in the three groups.
      Paired t-test and one-way ANOVA were used to analyze the collected data. RESULTS:
      Both types of therapeutic exercise programs significantly improved balance in
      single leg stance, star excursion test, and Berg balance scale test (P?0.05)
      compared to the control group. Besides, this was more significant in the ball
      training group (P?0.05). CONCLUSIONS: To improve balance in diabetic neuropathy,
      Swiss ball exercise is preferred compared to Frenkel training.

PMID- 27720358
TI  - Association Between Electronic Cigarette Marketing Near Schools and E-cigarette
      Use Among Youth.
AB  - PURPOSE: Electronic cigarettes (e-cigarettes) are now the most popular tobacco
      product among youth. Little is known about the relationship between exposure to e
      cigarette marketing at the point-of-sale and youth e-cigarette use. METHODS:
      Research staff collected data on e-cigarette availability and promotion in
      tobacco retailers within a half-mile of 41 schools participating in the 2014 New
      Jersey Youth Tobacco Survey. These data were linked with participant responses
      from the New Jersey Youth Tobacco Survey (n = 3,909) and log-Poisson regression
      models estimated adjusted prevalence ratios for ever and past-month e-cigarette
      use. RESULTS: Nearly a quarter of high school students in New Jersey have tried e
      cigarettes (24.1%) and 12.1% were past-month users. Prevalence was highest among
      males, non-Hispanic whites, and students who have used other tobacco products.
      After controlling for covariates and the clustered nature of the data, e
      cigarette retailer density around schools was positively associated with ever and
      past-month use of e-cigarettes (p < .05). E-cigarette advertising volume
      significantly increased the probability of being a past-month e-cigarette user
      (adjusted prevalence ratio: 1.03, p = .031). CONCLUSIONS: This study suggests
      that the point-of-sale environment around schools may contribute to e-cigarette
      use among youth. Policy efforts to restrict tobacco promotion at the point-of
      sale may play a role in reducing the use of e-cigarettes.

PMID- 27720360
TI  - Interleukin-1 antagonism in type 1 diabetes of long duration.

PMID- 27720361
TI  - Link between nasal carriage of Staphylococcus aureus and infected diabetic foot
      ulcers.
AB  - AIMS: Nasal carriage of Staphylococcus aureus in diabetic patients may be a risk
      factor for diabetic foot lesion infections. The aims of this study were to
      compare the genotypic profiles of S. aureus strains isolated from nares and
      diabetic foot ulcers (DFUs) using microarray technology. METHODS: Patients were
      included if they were admitted for diabetic foot infection (DFI) at any of three
      diabetology departments of Montpellier and Nimes University Hospitals between 1
      September 2010 to 30 June 2012. All S. aureus isolates were analyzed using
      oligonucleotides arrays; S. aureus resistance and virulence genes were determined
      and each isolate was affiliated to a clonal complex. RESULTS: The prevalence of
      S. aureus nasal carriage among the 276 included patients was 39.5% (n=109), while
      36.6% (n=101) had S. aureus at both sites (nares and foot wounds) and, of these
      patients, 65.3% of patients harboured the same strain at both sites. In addition,
      the spread of the methicillin-resistant S. aureus (MRSA) ST398 clone in DFI and
      its tropism for bone were also further confirmed. CONCLUSION: These findings
      appear to provide new arguments in favour of the systematic detection of nasal S.
      aureus carriage to anticipate the management of DFI.

PMID- 27720362
TI  - Cancer of Unknown Primary: a Cancer Registry Study of Factors Affecting Access to
      Diagnosis.
AB  - AIM: A potential impact of the centralisation of cancer services in the UK is
      difficulty in gaining access for members of the population living far from them.
      This could lead to delayed presentation of cancer with more advanced disease and
      clinical deterioration at diagnosis. A patient may be recorded in the cancer
      registry as having cancer of unknown primary (CUP) if the clinical state at
      presentation precludes investigation. Other patients may be so recorded if
      investigation identifies sites of metastatic tumour but the primary is not found.
      We hypothesised that the first group would include more patients who experienced
      difficulties in gaining access to health services through residing in deprived
      areas or through poorer geographical access to healthcare facilities. MATERIALS
      AND METHODS: We compared the diagnosis of CUP with a comparator tumour, carcinoma
      of the rectum, where diagnosis is facilitated by an alarm symptom and where
      variations in access are lower. Records from the Northern and Yorkshire Cancer
      Registry from 1994 to 2002 with ICD 10 C77-C80 (CUP, including categories where
      investigations may have been incomplete or no primary cancer was found) and C20
      (malignant neoplasm of rectum) were combined with travel time to services
      (primary care, secondary and tertiary services) and the Index of Multiple
      Deprivation. Logistic regression modelled predictors of CUP were compared with
      C20 and, within CUP, the odds of a histological basis of diagnosis. RESULTS: The
      registry classified 7428 patients as C80, 8849 as C77-C79, and 10 804 as C20.
      Compared with C20, the number of cases of C80 showed a statistically significant
      increasing trend with increasing travel time to primary care. Risk also increased
      strongly with age and deprivation. The results for C77-C79 were similar to those
      for C80, except that the travel time to primary care showed no effect.
      Considering all CUP alone, histological diagnosis significantly declined with
      travel time to the nearest hospital. There was no association with gender and the
      likelihood of histological diagnosis, but a marked decline with age, a downward
      trend with deprivation, and an increase when the nearest hospital was a cancer
      centre. CONCLUSIONS: These findings facilitate the understanding of factors
      associated with the group of patients that includes those with the least
      effective access to cancer services.

PMID- 27720364
TI  - Editorial overview: Growth and development: prokaryotes.

PMID- 27720363
TI  - Blood pressure and urolithiasis in children.
AB  - INTRODUCTION: Urolithiasis is a condition that is most commonly found in adults,
      but is becoming increasingly prevalent in children. Little is known about the
      relationship between blood pressure (BP) and urolithiasis in children.
      OBJECTIVES: The aim was to evaluate the relationship between urolithiasis and BP,
      and to determine the association of BP with 24-h urine parameters in children.
      METHODS: We retrospectively analyzed BP and 24-h urine data from children <18
      years with and without urolithiasis from 2004 to 2015 at a single tertiary
      center. Children with a diagnosis of non-glomerular hematuria without history of
      urolithiasis were chosen as the control group. Non-stone formers were excluded if
      they presented with any abnormal 24-h urine data or kidney disease. Casual BP, BP
      index (BPi), and 24-h urine parameters were compared between groups using t
      tests. Multiple regression analyses adjusting for age, sex and body mass index
      (BMI) z-score evaluated the association of BP with urolithiasis and urine
      electrolytes. RESULTS: The urolithiasis group (N = 71) was significantly older,
      taller and heavier than the non-stone former group (N = 53) (Table). Systolic BP
      and diastolic BP in stone formers were significantly greater than in non-stone
      formers, respectively (p = 0.019). Additionally, systolic BPi was significantly
      higher in the urolithiasis group (p = 0.03) but there was no significant
      difference in diastolic BPi (p = 0.45). Urolithiasis was a significant predictor
      of systolic BPi in the adjusted model (beta = 0.04, 95% CI 0.001-0.07). In stone
      formers, systolic BP and systolic BPi were directly associated with 24-h urine
      sodium, oxalate/1.73 m2, and uric acid (all p < 0.05). Urine calcium was not
      associated with any BP parameter. DISCUSSION: The findings are consistent with
      previous studies in adults that examined the correlation between blood pressure
      and kidney stones. The results of this study also showed that blood pressure was
      positively associated with urine sodium, oxalate, and uric acid. Interestingly,
      contrary to adult literature, our hypothesis which postulated that blood pressure
      would be associated with an increase in urine calcium was not supported by our
      findings. The small sample size is a study limitation and the use of healthy
      controls as a comparison would have been ideal. CONCLUSIONS: Blood pressure was
      directly associated with urolithiasis children. Greater BP values were also
      associated with abnormalities in 24-h urine oxalate, uric acid, and sodium
      values. Interestingly, BP was not associated with urine calcium in this
      population.

PMID- 27720365
TI  - Circumventing Brain Barriers: Nanovehicles for Retroaxonal Therapeutic Delivery.
AB  - In addition to safeguarding the central nervous system (CNS) from the vast
      majority of pathogens and toxins, transvascular barriers impose immense
      challenges to the delivery of beneficial cargo. A few toxins and neurotropic
      viruses capable of penetrating the brain have proved to be potentially valuable
      for neuron targeting and enhanced transfer of restorative medicine and
      therapeutic genes. Here we review molecular concepts and implications of the
      highly neurotropic tetanus toxin (TeTx) and botulinum neurotoxins (BoNTs) and
      their ability to infiltrate and migrate throughout neurons. We discuss recent
      applications of their detoxified variants as versatile nanovehicles for
      retroaxonal delivery of therapeutics to motor neurons and synapses. Continued
      advances in research on these remarkable agents in preclinical trials might
      facilitate their future use for medical benefit.

PMID- 27720366
TI  - Causes and estimated incidences of sex-chromosome misdiagnosis in preimplantation
      genetic diagnosis of aneuploidy.
AB  - Preimplantation genetic diagnosis of aneuploidy (PGD-A) with comprehensive
      chromosome analysis has been known to improve pregnancy outcomes. Accuracy in
      detecting sex chromosomes becomes important when selecting against embryos at
      risk for sex-linked disorders. A total of 21,356 PGD-A cycles consisting of day-3
      (cleavage) or day-5 (blastocyst) biopsies were received at the same laboratory
      for PGD-A via fluorescence in situ hybridization (FISH) or array comparative
      genome hybridization (aCGH) from multiple fertility centres. The misdiagnosis
      rates were 0.12% (Wilson 95% CI 0.05 to 0.25%) in day-3 FISH cycles, 0.48%
      (Wilson 95% CI 0.19 to 1.22%) in day-3 aCGH cycles and 0.0% (Wilson 95% CI 0 to
      0.26) in day-5 aCGH cycles. Although rare, the likely causative biological event
      for true misdiagnosis is embryonic XX/XY mosaicism. Reanalysis of 1219 abnormal
      cleavage-stage research embryos revealed a 73% incidence of minor and major
      mosaicism. Only four (0.3%) embryos were found to be diploid and contained XX and
      XY cells that could potentially account for the misdiagnosis of sex. Our
      investigation identified errors leading to misdiagnosis and their attribution to
      specific events during PGD-A testing. The reported misdiagnosis rates suggest
      that PGD-A for sex determination is highly accurate, particularly when using aCGH
      applied to blastocyst biopsies.

PMID- 27720367
TI  - Neuroendocrine Tumors of the Thymus: Analysis of Factors Affecting Survival in
      254 Patients.
AB  - BACKGROUND: Neuroendocrine tumors of the thymus (NETT) constitute less than 5% of
      all anterior mediastinal masses but are aggressive and lead to poor overall
      survival. This study was designed to evaluate factors that influence the
      prognosis of patients with NETT and the role of surgical intervention in
      survival. METHODS: We analyzed the Surveillance, Epidemiology, and End Results
      cancer database to identify patients with NETT. We performed univariate and
      multivariate analyses to identify prognostic factors among demographic, tumor,
      and treatment variables. RESULTS: In 254 patients identified with NETT, the
      median overall survival time was 73 months, with a 5-year survival rate of 56%.
      Patients who underwent surgical therapy had a significantly longer median
      survival time than did those who did not undergo surgical therapy (109 months vs
      46 months, p < 0.001). In multivariate analysis, surgical resection, Masaoka-Koga
      stage, and tumor size were significant predictors of survival. CONCLUSIONS: Our
      study found that surgical resection, Masaoka-Koga stage, and tumor size are
      significant prognostic factors in patients with NETT. Complete surgical resection
      continues, rightfully, to be the mainstay in the treatment of this rare disease.

PMID- 27720369
TI  - Extubation Failure in Neonates After Cardiac Surgery: Prevalence, Etiology, and
      Risk Factors.
AB  - BACKGROUND: The purpose of this study was to explore the prevalence, etiology,
      and risk factors of extubation failure (EF) in post-cardiac surgery neonates.
      METHODS: Neonates (30 days old or younger) who underwent cardiac surgery and were
      admitted to the cardiac intensive care unit between September 2010 and February
      2016 were included. The prevalence and etiology of EF, defined as reintubation
      within 48 hours, were reviewed. Demographic, operative, and perioperative data
      were retrospectively collected. Multiple logistic regression models were
      constructed to identify the risk factors for EF. RESULTS: The median age at
      surgery was 10 days. Extubation failure occurred in 25 of 156 cases (16.0%; 95%
      confidence interval: 10.6% to 22.7%), because of respiratory dysfunction (n =
      16), hemodynamic instability (n = 4), upper airway obstruction (n = 4), or
      gastrointestinal bleeding (n = 1). Subsequent extubations were successful in 17
      cases (68%) because of medical optimization of the causes of reintubation. The
      remaining 8 cases needed surgical reintervention, including tracheostomy and
      cardiac surgery. The inhospital mortality rate was 2.6%. In a bivariate analysis,
      younger age, airway diseases, ventilation before surgery, prolonged mechanical
      ventilation, and delayed sternal closure were associated with EF. The
      multivariable analysis identified airway diseases (adjusted odds ratio 18.2, 95%
      confidence interval: 3.8 to 88.6, p = 0.0003) and mechanical ventilation longer
      than 7 days (adjusted odds ratio 8.2, 95% confidence interval: 1.9 to 34.9, p =
      0.0046) as risk factors for EF. CONCLUSIONS: The prevalence of EF is relatively
      high in neonatal cardiac surgery. The etiologies can be diverse. Extubation of
      neonates at high risk after cardiac surgery, based on these possible risk
      factors, requires more diligent approaches.

PMID- 27720368
TI  - Screening for Frailty in Thoracic Surgical Patients.
AB  - BACKGROUND: The presence of frailty or prefrailty in older adults is a risk
      factor for postsurgical complications. The frailty phenotype can be improved
      through long-term resistance and aerobic training. It is unknown whether short
      term preoperative interventions targeting frailty will help to mitigate surgical
      risk. The purpose of this study was to determine the proportion of frail and
      prefrail patients presenting to a thoracic surgical clinic who could benefit from
      a frailty reduction intervention. METHODS: A prospective cohort study was
      performed at a single-site thoracic surgical clinic. Starting October 1, 2014,
      surgical candidates 60 years of age or older who consented to be screened were
      included. Patients were screened using an adapted version of Fried's phenotypic
      frailty criteria: weakness (grip strength), slow gait (15-foot walk),
      unintentional weight loss, self-reported exhaustion, and low self-reported
      physical activity (Physical Activity Scale for the Elderly). Prefrailty was
      identified when participants demonstrated one to two frailty characteristics;
      frailty was identified when participants demonstrated three to five frailty
      characteristics. RESULTS: Of 180 eligible patients, 126 consented, and 125
      completed screening. Thirty-nine participants (31%) were not frail, 71 (57%) were
      prefrail, and 15 (12%) were frail. Exhaustion was the most common frailty symptom
      (34%). Frailty prevalence did not significantly differ among men and women (men:
      10%, women: 14%; p = 0.75). CONCLUSIONS: We found a high proportion of prefrail
      and frail patients among patients deemed candidates for thoracic surgical
      procedures. This finding indicates that frailty may be underrecognized.
      Substantial numbers of patients may be considered for a presurgical frailty
      reduction intervention.

PMID- 27720370
TI  - How Does Mitral Valve Repair Fail in Patients With Prolapse?-Insights From
      Longitudinal Echocardiographic Follow-Up.
AB  - BACKGROUND: Repair of mitral regurgitation (MR) caused by prolapse has been well
      validated. Although favorable early and late results after repair have been
      reported, few data are available that mechanistically describe how a mitral
      repair fails beyond the mere need for mitral valve reoperation. We therefore
      sought to determine the modes of valve repair failure in patients who underwent
      surgical correction of MR caused by prolapse. METHODS: Between 2001 and 2015, 855
      patients underwent repair of MR caused by prolapse. Patients were a mean age of
      63.7 +/- 12.7 years, and 380 (44%) had bileaflet prolapse. The overall repair
      rate was 97.2%. These patients were monitored as part of a cohort initiative and
      underwent serial clinical and echocardiographic assessments at 1, 3 to 6, and 12
      months after the operation. Beyond the first year of the MR repair, patients were
      assessed by echocardiography every 1 to 2 years or when clinically indicated.
      Clinical and echocardiographic follow-up averaged 4.3 +/- 3.5 years. RESULTS:
      Freedom from recurrent MR of 2+ or higher was 92.4% +/- 1.3% at 5 years and 86.6%
      +/- 2.4% at 10 years. Overall, recurrent MR of 2+ or higher developed in 49
      patients (5.7%) at a mean of 3.1 +/- 2.5 years after the repair, of whom 14
      (1.6%) had recurrent MR of 3+ or 4+. Among patients with bileaflet prolapse,
      recurrent MR of 2+ or higher was observed in 24, of whom 9 had 3+ or 4+ MR., The
      development of recurrent MR of 2+ or higher was categorized as prolapse in 6 and
      nonprolapse in 43. Severe mitral stenosis occurred in 3 patients at 8.2 years
      after the MR repair. Mitral reoperation was ultimately performed in 21 patients.
      Patients who had recurrent MR 2+ or higher within the first year after the
      operation were more likely to undergo a subsequent mitral valve reoperation
      (incident rate ratio, 5.2 +/- 2.9; p = 0.003), although no association between
      recurrent MR and reoperation was observed after the first year. CONCLUSIONS:
      Severe MR after repair is rare, although some may have recurrent moderate MR.
      Patients who required a subsequent mitral valve reoperation were most likely to
      have recurrent MR of 2+ or higher within the first year after the operation.

PMID- 27720371
TI  - Delayed Sternal Closure in Infant Heart Surgery-The Importance of Where and When:
      An Analysis of the STS Congenital Heart Surgery Database.
AB  - BACKGROUND: Delayed sternal closure (DSC) is commonly used to optimize
      hemodynamic stability after neonatal and infant heart surgery. We hypothesized
      that duration of sternum left open (SLO) was associated with rate of infection
      complications, and that location of sternal closure may mitigate infection risk.
      METHODS: Infants (age <=365 days) undergoing index operations with
      cardiopulmonary bypass and DSC at STS Congenital Heart Surgery Database centers
      (from 2007 to 2013) with adequate data quality were included. Primary outcome was
      occurrence of infection complication, defined as one or more of the following:
      endocarditis, pneumonia, wound infection, wound dehiscence, sepsis, or
      mediastinitis. Multivariable regression models were fit to assess association of
      infection complication with: duration of SLO (days), location of DSC procedure
      (operating room versus elsewhere), and patient and procedural factors. RESULTS:
      Of 6,127 index operations with SLO at 100 centers, median age and weight were 8
      days (IQR, 5-24) and 3.3 kg (IQR, 2.9-3.8); 66% of operations were STAT morbidity
      category 4 or 5. At least one infection complication occurred in 18.7%, compared
      with 6.6% among potentially eligible neonates and infants without SLO. Duration
      of SLO (median, 3 days; IQR, 2-5) was associated with an increased rate of
      infection complications (p < 0.001). Location of DSC procedure was operating room
      (16%), intensive care unit (67%), or other (17%). Location of DSC was not
      associated with rate of infection complications (p = 0.45). CONCLUSIONS: Rate of
      occurrence of infectious complications is high among infants with sternum left
      open following cardiac surgery. Longer duration of SLO is associated with
      increased infection complications.

PMID- 27720372
TI  - How to perform 3D reconstruction of skull base tumours.
AB  - The surgical management of skull base lesions is difficult due to the complex
      anatomy of the region and the intimate relations between the lesion and adjacent
      nerves and vessels. Minimally invasive approaches are increasingly used in skull
      base surgery to ensure an optimal functional prognosis. Three-dimensional (3D)
      computed tomography (CT) reconstruction facilitates surgical planning by
      visualizing the anatomical relations of the lesions in all planes (arteries,
      veins, nerves, inner ear) and simulation of the surgical approach in the
      operating position. Helical CT angiography is performed with optimal timing of
      the injection in terms of tumour and vessel contrast enhancement. 3D definition
      of each structure is based on colour coding by automatic thresholding (bone,
      vessels) or manual segmentation on each slice (tumour, nerves, inner ear).
      Imaging is generally presented in 3 dimensions (superior, coronal, sagittal) with
      simulation of the surgical procedure (5 to 6 reconstructions in the operating
      position at different depths).

PMID- 27720373
TI  - Diagnostic and prognostic contribution of laryngeal electromyography in
      unilateral vocal-fold immobility in adults.
AB  - OBJECTIVES: To study the diagnostic and prognostic contribution of laryngeal
      electromyography in unilateral vocal-fold immobility in adults. MATERIAL AND
      METHODS: A retrospective study included patients with unilateral vocal-fold
      immobility undergoing laryngeal electromyography between 2007 and 2015.
      Neurogenic, normal or myogenic findings were compared to the clinical aspect.
      Prognosis for recovery was assessed from motor unit potentials on laryngeal
      electromyography, and compared to subsequent progress on laryngoscopy. RESULTS:
      Sixty-three patients (mean age, 59 years) were initially included; 2 were
      subsequently excluded from analysis. Mean time from onset of immobility to
      laryngeal electromyography was 7 months. 85% of the 61 patients showed neurogenic
      findings, indicating neural lesion; 13% showed normal electromyography,
      indicating cricoarytenoid joint ankylosis; and 1 patient showed a myogenic
      pattern. Neurogenic cases were usually secondary to cervical surgery. Thirty
      eight patients were followed up. In total, 75% of patients showing reinnervation
      potentials recovered. The positive predictive value of laryngeal electromyography
      was 69.2%. CONCLUSION: Laryngeal electromyography is effective in specifying the
      origin of unilateral vocal-fold immobility in adults. It also has a prognostic
      role, lack of reinnervation potentials being a possible indication for early
      medialization surgery.

PMID- 27720374
TI  - Trauma networks and rural trauma.

PMID- 27720375
TI  - Coracoid bone block fixation with cortical buttons: An alternative to screw
      fixation?
AB  - BACKGROUND: The purpose of this study was to evaluate suture button fixation in a
      bone block (Bristow and Latarjet) procedure. We hypothesize that (1) cortical
      button fixation will allow predictable and reproducible bone union and (2)
      minimize the complications reported with screw fixation. MATERIALS AND METHODS:
      Seventy patients (mean age, 27 years) underwent an arthroscopic bone block
      procedure with a guided surgical approach and suture button fixation for
      recurrent anterior shoulder instability. There were two groups of patients: 35
      Bristow procedures (group A) and 35 Latarjet procedures (group B). Bone graft
      union and positioning accuracy were assessed by postoperative computed tomography
      imaging at 2 weeks and 6 months, respectively. RESULTS: The coracoid graft was
      positioned below the equator in 93% and strictly tangential to the glenoid
      surface in 94% of the cases. Bone healing was observed in 83% of the cases
      (58/70) with 74% bone union in group A and 91% in group B. Neurologic and
      hardware complications, classically reported with screw fixation, were not
      observed with this novel fixation method. CONCLUSIONS: (1) Suture button fixation
      can be an alternative to screw fixation, obtaining bone block union, (2) in the
      lying position (Latarjet) bone healing was better than in the standing position
      (Bristow), and (3) complications classically reported with screw fixation were
      not observed. LEVEL OF EVIDENCE: Level IV.

PMID- 27720376
TI  - Anterior cervical interbody fusion using polyetheretherketone cage filled with
      synthetic bone graft in acute cervical spine injury.
AB  - PURPOSE: The aim of this study was to assess the interbody fusion rate for
      patients treated by anterior cervical interbody fusion (ACIF) using
      polyetheretherketone (PEEK) cages filled with synthetic bone graft in acute
      cervical spine injury. MATERIALS AND METHODS: Twenty-nine patients (mean age: 49
      years) with monosegmental instability due to cervical spine injury were followed.
      We assessed the rate of and time to interbody fusion at 1-year follow-up. In case
      of secondary displacement, we analysed its causes and surgical management.
      RESULTS: The rate of fusion was 86.2%. The mean time to fusion was 7.2 months.
      Interbody fusion was observed at 3 months in 4 patients, at 6 months in 14 and at
      1 year in 7. Four patients had secondary displacement within 3 months.
      CONCLUSION: ACIF with a PEEK cage filled with synthetic bone graft seems to be an
      alternative to iliac crest bone graft with no morbidity related to the harvest
      site.

PMID- 27720378
TI  - Metformin: Candidate host-directed therapy for tuberculosis in diabetes and non
      diabetes patients.
AB  - Despite major advances in tuberculosis (TB) control, TB continues to be a leading
      cause of death worldwide. The discovery of new anti-TB treatment drugs and
      regimens that target drug-sensitive and drug-resistant TB are being complemented
      with a search for adjunct host-directed therapies that synergize for
      Mycobacterium tuberculosis (Mtb) elimination. The goal of host-directed therapies
      is to boost immune mechanisms that diminish excess inflammation to reduce lung
      tissue damage and limit Mtb growth. Metformin is the most commonly-used
      medication for type 2 diabetes, and a candidate for host-directed therapy for TB.
      Preliminary data suggests metformin may be beneficial for TB control by reducing
      the deleterious inflammation associated with immune pathology and enhancing the
      anti-mycobacterial activity of immune cells. In this review I summarize current
      findings, knowledge gaps and the potential benefits as well as points of caution
      for using metformin as adjunct therapy for TB in patients with and without type 2
      diabetes.

PMID- 27720379
TI  - Texas Tuberculosis Research Symposium 2016: Research and clinical collaboration
      within the state of Texas towards elimination of TB.

PMID- 27720377
TI  - Predictive value of serum bradykinin and desArg9-bradykinin levels for
      chemotherapeutic responses in active tuberculosis patients: A retrospective case
      series.
AB  - BACKGROUND: There is an urgent need for methods that can rapidly and accurately
      assess therapeutic responses in patients with active tuberculosis (TB) in order
      to predict treatment outcomes. Exposure to bacterial pathogens can rapidly
      activate the plasma contact system, triggering the release of bradykinin (BK) and
      its metabolite desArg9-bradykinin (DABK) to induce inflammation and innate immune
      responses. We hypothesized that serum BK and DABK levels might act as sensitive
      immune response signatures for changes in Mycobacterium tuberculosis (Mtb)
      burden, and therefore examined how serum levels of these markers corresponded
      with anti-TB therapy in a small cohort of active TB cases. METHODS: Nanotrap Mass
      Spectrometry (MS) was used to analyze serial blood specimens from 13 HIV-negative
      adults with microbiologically confirmed active TB who were treated with first
      line anti-TB chemotherapy. MS signal for BK (m/z 1060.5) and DABK (m/z 904.5)
      serum peptides were evaluated at multiple time-points (before, during, and after
      treatment) to evaluate how BK and DABK levels corresponded with disease status.
      RESULTS: Serum BK levels declined from pretreatment baseline levels during the
      early stage anti-TB therapy (induction phase) and tended to remain below baseline
      levels during extended treatment (consolidation phase) and after therapy
      completion. BK levels were consistent with induction phase sputum culture
      conversions indicative of decreased Mtb burden reflecting good treatment
      responses. Serum DABK levels tended to increase during the induction phase and
      decrease at consolidation and post-therapy time points, which may indicate a
      shift from active disease to chronic inflammation to a disease free state.
      Elevated BK and DABK levels after treatment completion in one patient may be
      related to the subsequent recurrent TB disease. CONCLUSIONS: Our pilot data
      suggests that changes in the circulating BK and DABK levels in adult TB patients
      can be used as potential surrogate markers of the host response both early and
      late in anti-TB treatment for both pulmonary and extrapulmonary TB patients. We
      will further exploit these host-response signatures in the future as biomarkers
      in combination with other clinical and microbiologic tools which may improve
      treatment efficacy and facilitate the development of host-directed therapy.

PMID- 27720380
TI  - Twenty-four hour Holter monitoring in finishing cattle housed outdoors.
AB  - INTRODUCTION: Atrial premature complexes have been reported to be the most common
      arrhythmia in cattle and is suspected to be secondary to systemic disease,
      especially gastrointestinal disease. In order to properly identify pathologic
      arrhythmia in cattle, the normal rhythm and arrhythmia prevalence should be
      defined. The objective of this study was to determine the normal heart rate,
      rhythm, number of ventricular premature complexes (VPCs), and atrial premature
      complexes (APCs) in unrestrained Angus steers. ANIMALS: Twenty-seven client owned
      steers with unremarkable physical examinations and serum biochemical analyses
      were used. MATERIALS AND METHODS: Twenty-four hour Holter monitors, attached by a
      custom-made harness, were retrospectively evaluated. Three lead
      electrocardiographic registrations of good quality and normal sinus rhythm were
      obtained from all steers in the study. RESULTS: The mean heart rate was 66.8 bpm
      +/- 16.4 bpm. Ventricular premature complexes were rare (noted in 14.8% of
      steers), and APCs were common (noted in 85% of the steers). Simple second degree
      AV block was observed in 18.5% of the steers. CONCLUSION: In summary, healthy
      steers have rare single VPCs, although it is possible for an individual animal to
      have apparent more frequent VPCs. Mean heart rate varies with a diurnal pattern
      similar to other species. Atrial premature complexes are the most prevalent
      abnormality observed in feedlot steers.

PMID- 27720381
TI  - Borrelia burgdorferi DNA absent, multiple Rickettsia spp. DNA present in ticks
      collected from a teaching forest in North Central Florida.
AB  - Tick-borne diseases are an emerging public health threat in the United States. In
      Florida, there has been public attention directed towards the possibility of
      locally acquired Borrelia burgdorferi sensu stricto, the causative agent of Lyme
      disease, in association with the lone star tick. The aim of this study was to
      determine the prevalence of ticks and the pathogens they carry and potentially
      transmit, such as B. burgdorferi, in a highly utilized teaching and research
      forest in North Central Florida. Ticks were collected by dragging and flagging
      methods over a four month period in early 2014, identified, and tested by PCR for
      multiple pathogens including Anaplasma, Borrelia, Rickettsia, and Ehrlichia
      species. During the study period the following ticks were collected: 2506 (96.5%)
      Amblyomma americanum L., 64 (2.5%) Ixodes scapularis Say, 19 (0.7%) Dermacentor
      variabilis Say, and 5 (0.2%) Ixodes affinis Neuman. Neither Borrelia spp. (0/846)
      nor Anaplasma spp. (0/69; Ixodes spp. only) were detected by PCR in any of the
      ticks tested. However, Rickettsia DNA was present in 53.7% (86/160), 62.5%
      (40/64), 60.0% (3/5) and 31.6% (6/19) of A. americanum, I. scapularis, I. affinis
      and D. variabilis, respectively. Furthermore, E. chaffeensis and E. ewingii DNA
      were detected in 1.3% and 4.4% of adult A. americanum specimens tested,
      respectively. Although receiving an A. americanum bite is likely in wooded areas
      in North Central Florida due to the abundance of this tick, the risk of
      contracting a tick-borne pathogen in this specific area during the spring season
      appears to be low. The potential for pathogen prevalence to be highly variable
      exists, even within a single geographical site and longitudinal studies are
      needed to assess how tick-borne pathogen prevalence is changing over time in
      North Central Florida.

PMID- 27720382
TI  - Detection of Candidatus Neoehrlichia mikurensis and Ehrlichia muris in Estonian
      ticks.
AB  - So far neglected bacteria like Candidatud Neoehrlichia mikurensis and Ehrlichia
      muris-like agents get increased attention in the recent past. Ixodid ticks were
      demonstrated to harbor both of these pathogens. Estonia is populated by two
      medically important tick species, I. ricinus and I. persulcatus. In this study
      the presence of E. muris and Candidatus N. mikurensis in these two tick species
      was investigated. Tick DNA was analyzed by nested PCR and subsequent sequencing
      for the presence of 16S rRNA of E. muris and Candidatus N. mikurensis. Positive
      samples were further confirmed by amplification and sequencing of the partial
      groESL-operon. The obtained partial groESL sequences were used for construction
      of a maximum likelihood tree. In total, 776 ticks from 36 collection sites
      situated in 7 counties on the mainland of Estonia and 2 sites situated in one
      county on the island Saaremaa were collected. 548 were I. ricinus and 228 were I.
      persulcatus. Only in 5 counties (11 sites) samples positive for the
      Anaplasmataceae 16S rRNA gene were found. The percentage of Candidatus N.
      mikurensis positive ticks varied from 1% to 9.1% at different sites. In Eastern
      and South-Eastern Estonia, the area where I. ricinus and I. persulcatus are
      sympatric, no Candidatus N. mikurensis was found. Ticks carrying E. muris were
      found in three counties, the site-specific percentage of positive ticks varied
      from 1.2% to 25.6%. This is the first study revealing the presence of Candidatus
      N. mikurensis and E. muris in Estonian ticks. Candidatus N. mikurensis was found
      only in the western part of the country exclusively in I. ricinus and the
      phylogenetic analysis revealed close relatedness of the Estonian sequences to
      other European Candidatus N. mikurensis strains. E. muris was detected mostly in
      I. persulcatus and only in one I. ricinus in the sympatric area of both tick
      species. This is in correspondence with the observation that this pathogen is
      more often found in I. persulcatus than in I. ricinus. This study demonstrates
      the presence of Candidatus N. mikurensis and E. muris in Estonian ticks and
      highlights the necessity to raise awareness of symptoms by healthcare
      professionals.

PMID- 27720384
TI  - Reply.

PMID- 27720383
TI  - Impact of a combination of full coverage stenting and proximal optimization
      technique on long term outcome for unprotected distal left main disease.
AB  - BACKGROUND: There is no consensual opinion regarding the percutaneous coronary
      intervention (PCI) procedure for unprotected distal left main (UDLM) lesion.
      METHODS: Between April 2005 and August 2011, 586 consecutive patients with UDLM
      stenosis treated with drug-eluting stents were recruited for this study to
      clarify the impact of combination of full-coverage stenting and proximal
      optimization technique (POT) for UDLM lesion. An optimal strategy of full
      coverage stenting and POT was performed in 353 patients and the other 233
      patients were not optimally treated. Major adverse cardiovascular events (MACEs)
      were defined as all-cause death, myocardial infarction, or target lesion
      revascularization (TLR) during follow-up period. TLRs were also evaluated for
      main branch (MB) restenosis. RESULTS: At 1615days of follow-up, MACE occurred in
      166 (28.3%) patients. The occurrence of MACE and TLR had a trend to being lower
      in the optimal strategy [propensity score-adjusted HR, 0.73 (95% CI, 0.53-1.01),
      p=0.05 and propensity score-adjusted HR, 0.69 (95% CI, 0.46-1.02), p=0.06,
      respectively]. TLR of the MB occurred significantly less frequently in the
      optimal strategy [propensity score-adjusted HR, 0.34 (95% CI, 0.15-0.76),
      p=0.008]. Cardiac death occurred in 28 (4.8%) patients. There was no significant
      difference in cardiac death between the two groups. These results were sustained
      after propensity-score matching. CONCLUSIONS: An optimal PCI strategy of full
      coverage stenting and POT might be effective for UDLM lesion to reduce the
      occurrence of MACE, especially driven by TLR of the MB.

PMID- 27720386
TI  - Catatonic and Psychotic Symptoms Owing to the Trauma of Captivity in a Cult
      Environment.

PMID- 27720385
TI  - Use of Granulocyte Colony-Stimulating Factor in a Neutropenic HIV-Infected
      Patient on Clozapine.

PMID- 27720387
TI  - [Brazilian Consensus on perioperative hemodynamic therapy goal guided in patients
      undergoing noncardiac surgery: fluid management strategy - produced by the Sao
      Paulo State Society of Anesthesiology (Sociedade de Anestesiologia do Estado de
      Sao Paulo - SAESP)].

PMID- 27720389
TI  - Expanded bi-pedicled "sleeve" flap for reconstruction of the upper extremity
      after large circumferential nevus excision in children.
AB  - BACKGROUND: Large congenital melanocytic nevi entail significant medical and
      cosmetic ramifications for patients and families. Reconstruction is a challenging
      endeavor, especially when the lesion is present on the limbs. The literature
      describes various methods by which a plastic surgeon can address reconstruction;
      yet, to date, there has been no series describing a method that provides
      consistent results with low complication rates. In this study, we describe our
      surgical technique for reconstruction of the upper extremity after excision of
      large circumferential CNM with a pre-expanded bi-pedicled flap, namely the
      "sleeve" flap. METHODS: A systematic review of our database of pediatric patients
      treated for large and giant nevi was performed. Patients with large and giant
      circumferential upper extremity nevi were retrieved, and their charts reviewed
      for demographics, number of procedures performed, duration of follow-up, and
      complications. RESULTS: Over a course of 12 years, eight patients with large or
      giant circumferential nevi of the upper extremity were treated at our institution
      with "sleeve" flap reconstruction. Mean follow-up time was 36 months. A single
      complication was seen. All reconstructions achieved satisfactory results, both
      functionally and cosmetically. DISCUSSION: We describe our surgical approach for
      treating upper extremity large and giant circumferential nevi with pre-expanded
      bi-pedicled "sleeve" flaps. When properly planned and executed, this technique
      enables successful treatment of large and giant nevi of the arm and the forearm.
      Although arduous and complex, the process yields excellent aesthetic results with
      low complication rates. This technique is promising as the reconstructive option
      of choice for these difficult lesions.

PMID- 27720390
TI  - Succession Planning and Management: The Backbone of the Radiology Group's Future.
AB  - The transition of leadership within radiology practices is often not a planned
      replacement process with formal development of potential future leaders. To
      ensure their ongoing success, however, practices need to develop comprehensive
      succession plans that include a robust developmental program for potential
      leaders consisting of mentoring, coaching, structured socialization, 360-degree
      feedback, developmental stretch assignments, job rotation, and formal education.
      Succession planning and leadership development will be necessary in the future
      for a practice to be successful in its business relationships and to be
      financially viable.

PMID- 27720391
TI  - Streptococcus pneumoniae cellulitis.

PMID- 27720392
TI  - Facial tumours in a patient with multiple neoplasms.

PMID- 27720388
TI  - Insights About Striatal Circuit Function and Schizophrenia From a Mouse Model of
      Dopamine D2 Receptor Upregulation.
AB  - The dopamine hypothesis of schizophrenia is supported by a large number of
      imaging studies that have identified an increase in dopamine binding at the D2
      receptor selectively in the striatum. We review a decade of work using a
      regionally restricted and temporally regulated transgenic mouse model to
      investigate the behavioral, molecular, electrophysiological, and anatomical
      consequences of selective D2 receptor upregulation in the striatum. These studies
      have identified new and potentially important biomarkers at the circuit and
      molecular level that can now be explored in patients with schizophrenia. They
      provide an example of how animal models and their detailed level of
      neurobiological analysis allow a deepening of our understanding of the
      relationship between neuronal circuit function and symptoms of schizophrenia, and
      as a consequence generate new hypotheses that are testable in patients.

PMID- 27720393
TI  - Utility of virtual reality environments to examine physiological reactivity and
      subjective distress in adults who stutter.
AB  - PURPOSE: Virtual reality environments (VREs) allow for immersion in speaking
      environments that mimic real-life interactions while maintaining researcher
      control. VREs have been used successfully to engender arousal in other disorders.
      The purpose of this study was to investigate the utility of virtual reality
      environments to examine physiological reactivity and subjective ratings of
      distress in persons who stutter (PWS). METHOD: Subjective and objective measures
      of arousal were collected from 10PWS during four-minute speeches to a virtual
      audience and to a virtual empty room. RESULTS: Stuttering frequency and
      physiological measures (skin conductance level and heart rate) did not differ
      across speaking conditions, but subjective ratings of distress were significantly
      higher in the virtual audience condition compared to the virtual empty room.
      CONCLUSION: VREs have utility in elevating subjective ratings of distress in PWS.
      VREs have the potential to be useful tools for practicing treatment targets in a
      safe, controlled, and systematic manner.

PMID- 27720394
TI  - G Protein-coupled Receptor Kinase 2 (GRK2) Promotes Breast Tumorigenesis Through
      a HDAC6-Pin1 Axis.
AB  - In addition to oncogenic drivers, signaling nodes can critically modulate cancer
      related cellular networks to strength tumor hallmarks. We identify G-protein
      coupled receptor kinase 2 (GRK2) as a relevant player in breast cancer. GRK2 is
      up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a
      proportion of invasive ductal carcinoma patients. Increased GRK2 functionality
      promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6)
      leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of
      tumor progression, thereby enhancing its stability and functional interaction
      with key mitotic regulators. Interestingly, a correlation between GRK2 expression
      and Pin1 levels and de-acetylation status is detected in breast cancer patients.
      Activation of the HDAC6-Pin1 axis underlies the positive effects of GRK2 on
      promoting growth factor signaling, cellular proliferation and anchorage
      independent growth in both luminal and basal breast cancer cells. Enhanced GRK2
      levels promote tumor growth in mice, whereas GRK2 down-modulation sensitizes
      cells to therapeutic drugs and abrogates tumor formation. Our data suggest that
      GRK2 acts as an important onco-modulator by strengthening the functionality of
      key players in breast tumorigenesis such as HDAC6 and Pin1.

PMID- 27720397
TI  - A local mechanism by which alcohol consumption causes cancer.
AB  - Epidemiological data indicate that 5.8% of cancer deaths world-wide are
      attributable to alcohol consumption. The risk of cancer is higher in tissues in
      closest contact on ingestion of alcohol, such as the oral cavity, pharynx and
      esophagus. However, since ethanol is not mutagenic and the carcinogenic
      metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not
      clear why alcohol use preferentially exerts a local carcinogenic effect. It is
      well known that ethanol causes cell death at the concentrations present in
      alcoholic beverages; however, this effect may have been overlooked because dead
      cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of
      ethanol on the cells lining the oral cavity, pharynx and esophagus activates the
      division of the stem cells located in deeper layers of the mucosa to replace the
      dead cells. Every time stem cells divide, they become exposed to unavoidable
      errors associated with cell division (e.g., mutations arising during DNA
      replication and chromosomal alterations occurring during mitosis) and also become
      highly vulnerable to the genotoxic activity of DNA-damaging agents (e.g.,
      acetaldehyde and tobacco carcinogens). Alcohol consumption may increase the risk
      of developing cancer of the oral cavity, pharynx and esophagus by promoting the
      accumulation of cell divisions in the stem cells that maintain these tissues in
      homeostasis. Understanding the mechanisms of carcinogenicity of alcohol is
      important to reinforce the epidemiological evidence and to raise public awareness
      of the strong link between alcohol consumption and cancer.

PMID- 27720395
TI  - Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress
      Pathological Ocular Angiogenesis.
AB  - Neovascular eye diseases including retinopathy of prematurity, diabetic
      retinopathy and age-related-macular-degeneration are major causes of blindness.
      Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic
      retinopathy independent of its peroxisome proliferator-activated receptor
      (PPAR)alpha agonist lipid lowering effect. The mechanism is unknown. Fenofibrate
      binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity
      than to PPARalpha. CYP2C metabolizes omega-3 long-chain polyunsaturated fatty
      acids (LCPUFAs). While omega-3 LCPUFA products from other metabolizing pathways
      decrease retinal and choroidal neovascularization, CYP2C products of both omega-3
      and omega-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate
      inhibits retinopathy by reducing CYP2C omega-3 LCPUFA (and omega-6 LCPUFA) pro
      angiogenic metabolites. Fenofibrate reduced retinal and choroidal
      neovascularization in PPARalpha-/-mice and augmented omega-3 LCPUFA protection
      via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal
      neovascularization in mice overexpressing human CYP2C8 in endothelial cells and
      reduced plasma levels of the pro-angiogenic omega-3 LCPUFA CYP2C8 product, 19,20
      epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate
      induced suppression of angiogenesis ex vivo and suppression of endothelial cell
      functions in vitro. In summary fenofibrate suppressed retinal and choroidal
      neovascularization via CYP2C inhibition as well as by acting as an agonist of
      PPARalpha. Fenofibrate augmented the overall protective effects of omega-3
      LCPUFAs on neovascular eye diseases.

PMID- 27720398
TI  - Comparative genome analysis of two Streptococcus phocae subspecies provides novel
      insights into pathogenicity.
AB  - Streptococcus phocae is a beta-hemolytic, Gram-positive bacterium that was first
      isolated in Norway from clinical specimens of harbor seal (Phoca vitulina)
      affected by pneumonia or respiratory infection, and in 2005, this bacterium was
      identified from disease outbreaks at an Atlantic salmon farm. A recent
      comparative polyphasic study reclassified Streptococcus phocae as subsp. phocae
      and subsp. salmonis, and there are currently two S. phocae NCBI sequencing
      projects for the type strains ATCC 51973T and C-4T. The present study compared
      these genome sequences to determine shared properties between the pathogenic
      mammalian and fish S. phocae subspecies. Both subspecies presented genomic
      islands, prophages, CRISPRs, and multiple gene activator and RofA regulator
      regions that could play key roles in the pathogenesis of streptococcal species.
      Likewise, proteins possibly influencing immune system evasion and virulence
      strategies were identified in both genomes, including Streptokinases,
      Streptolysin S, IgG endopeptidase, Fibronectin binding proteins, Daunorubicin,
      and Penicillin resistance proteins. Comparative differences in phage, non-phage,
      and genomic island sequences may form the genetic basis for the virulence,
      pathogenicity, and ability of S. phocae subsp. salmonis to infect and cause
      disease in Atlantic salmon, in contrast to S. phocae subsp. phocae. This
      comparative genomic study between two S. phocae subsp. provides novel insights
      into virulence factors and pathogenicity, offering important information that
      will facilitate the development of preventive and treatment measures against this
      pathogen.

PMID- 27720396
TI  - Fecal Microbiota-based Therapeutics for Recurrent Clostridium difficile
      Infection, Ulcerative Colitis and Obesity.
AB  - The human gut microbiome is a complex ecosystem of fundamental importance to
      human health. Our increased understanding of gut microbial composition and
      functional interactions in health and disease states has spurred research efforts
      examining the gut microbiome as a valuable target for therapeutic intervention.
      This review provides updated insight into the state of the gut microbiome in
      recurrent Clostridium difficile infection (CDI), ulcerative colitis (UC), and
      obesity while addressing the rationale for the modulation of the gut microbiome
      using fecal microbiota transplant (FMT)-based therapies. Current microbiome-based
      therapeutics in pre-clinical or clinical development are discussed. We end by
      putting this within the context of the current regulatory framework surrounding
      FMT and related therapies.

PMID- 27720399
TI  - Becoming a sexual being: The 'elephant in the room' of adolescent brain
      development.
AB  - The onset of adolescence is a time of profound changes in motivation, cognition,
      behavior, and social relationships. Existing neurodevelopmental models have
      integrated our current understanding of adolescent brain development; however,
      there has been surprisingly little focus on the importance of adolescence as a
      sensitive period for romantic and sexual development. As young people enter
      adolescence, one of their primary tasks is to gain knowledge and experience that
      will allow them to take on the social roles of adults, including engaging in
      romantic and sexual relationships. By reviewing the relevant human and animal
      neurodevelopmental literature, this paper highlights how we should move beyond
      thinking of puberty as simply a set of somatic changes that are critical for
      physical reproductive maturation. Rather, puberty also involves a set of
      neurobiological changes that are critical for the social, emotional, and
      cognitive maturation necessary for reproductive success. The primary goal of this
      paper is to broaden the research base and dialogue about adolescent romantic and
      sexual development, in hopes of advancing understanding of sex and romance as
      important developmental dimensions of health and well-being in adolescence.

PMID- 27720400
TI  - Evaluation of quail and turkey egg yolk for cryopreservation of Nili-Ravi buffalo
      bull semen.
AB  - Egg yolk is used as a cryoprotectant for semen in different mammalian species
      including buffalo. Egg yolk from different sources may affect freezability of
      buffalo bull semen. Quail egg yolk (QEY) and turkey egg yolk (TEY) in Tris-citric
      acid extender was evaluated for post-thaw quality and in vivo fertility rate of
      cryopreserved buffalo bull semen. Ejaculates were collected on weekly basis from
      six Nili-Ravi buffalo bulls (12 ejaculates/bull) for a period of 6 weeks and
      diluted at 37  degrees C with tris-citric egg yolk extender (50 * 106 motile
      spermatozoa mL-1) containing different levels of QEY or TEY (5%, 10%, 15%, and
      20%) or 20% chicken egg yolk (CEY; controls) and cryopreserved. Percent post-thaw
      sperm motility (48.3 +/- 3.8), plasma membrane integrity (67.9 +/- 5.3),
      live/dead ratio (68.2 +/- 5.0), and viability (50.5 +/- 3.7) were recorded higher
      (P < 0.05) in extender containing 5% QEY compared with control. However, TEY at
      10% in extender improved (P < 0.05) the post-thaw sperm motility (57.5 +/- 5.2),
      plasma membrane integrity (53.5 +/- 4.5), livability (75.3 +/- 6.0), and
      viability (73.5 +/- 6.5) compared with higher concentrations of TEY and controls
      (20% CEY). The chromatin damage (2.0 +/- 0.9) and intracellular enzymes, glutamic
      oxaloacetic transaminase (24.8 +/- 3.5) and lactic dehydrogenase (77.7 +/- 4.5),
      release were lower (P < 0.05) in extender containing 10% TEY compared with the
      controls. Invivo fertility was compared after artificial insemination with semen
      from two buffalo bulls that was cryopreserved in extenders containing 5% QEY, 10%
      TEY, or 20% CEY. A total of 600 inseminations (200 inseminations per extender)
      were recorded; the overall fertility rate was significantly higher (P < 0.05)
      with semen cryopreserved in extender containing 5% QEY (57.5 vs. 42%) and 10% TEY
      (57.5 vs. 42%). compared with 20% chiken egg yolk. In conclusion, QEY at 5% and
      TEY at 10% offers advantages over 20% CEY in terms of in vitro post-thaw semen
      quality and in vivo fertility of buffalo.

PMID- 27720401
TI  - Schizophrenia and metabolic dysregulation: shared roots?

PMID- 27720402
TI  - The association between first-episode psychosis and abnormal glycaemic control:
      systematic review and meta-analysis.
AB  - BACKGROUND: Schizophrenia might share intrinsic inflammatory disease pathways
      with type 2 diabetes. We aimed to assess whether first-episode psychosis, which
      could be described as developing schizophrenia, is associated with prediabetic
      markers, or developing diabetes, to determine whether intrinsic disease links
      could cause the disorders to develop in unison. We hypothesised that biochemical
      measures of prediabetic states would be more common in antipsychotic naive
      patients with first-episode psychosis than in healthy matched controls. METHODS:
      For this systematic review and meta-analysis, using PRISMA criteria, we searched
      Embase, MEDLINE, PsycINFO, Web of Science, and Google Scholar for clinical
      studies published between database inception and Jan 6, 2016. We assessed case
      control studies with biochemical assessment of prediabetic states in patients
      with first-episode psychosis alongside matched controls. We sought data at the
      summary estimate level. Several measurements were used to test for prediabetes,
      including fasting plasma glucose, insulin resistance (measured by the Homeostatic
      Model Assessment), and impaired glucose tolerance. We calculated standardised
      mean differences for each outcome. We used the inverse variance method, for which
      the weight given to each study was the inverse of the variance of the effect
      estimate. For dichotomous outcomes, we entered the number of events and number in
      each group into RevMan 5.3 and used the Mantel-Haenszel method to pool studies.
      FINDINGS: We identified 1436 studies, of which 12 were included in final
      analysis, including 1137 participants. Pooled analyses found first-episode
      psychosis to be related to insulin resistance (mean difference 0.30 [95% CI 0.18
      to 0.42]), impaired glucose tolerance (mean difference 1.31 [0.37 to 2.25]), and
      the number of patients with impaired glucose tolerance (odds ratio 5.44 [2.63 to
      11.27]), but not fasting plasma glucose (mean difference 0.03 mmol/L [-0.04 to
      0.09]). INTERPRETATION: Our findings suggest a potential link between prediabetic
      markers, in particular impaired glucose tolerance and insulin resistance, and
      first-episode psychosis. However, we cannot establish causality, and the studies
      contributing to this review were at some risk of bias. Nevertheless, the findings
      might help to explain the increased prevalence of type 2 diabetes in patients
      with schizophrenia and could have implications for the management of patients
      with schizophrenia. FUNDING: None.

PMID- 27720403
TI  - Effect of daily calcitriol supplementation with and without calcium on disease
      regression in non-alcoholic fatty liver patients following an energy-restricted
      diet: Randomized, controlled, double-blind trial.
AB  - BACKGROUND & AIMS: Despite evidence for beneficial effects of vitamin D, to our
      knowledge, no study has compared the effects of calcium supplementation with
      vitamin D on non-alcoholic fatty liver disease (NAFLD) regression during a hypo
      energetic program. We compared the effect of the vitamin D supplementation with
      and without calcium on anthropometric measures and biochemical parameters in
      NAFLD patients during a weight-loss program. METHODS: A 12-week, randomized,
      controlled, double-blind trial was conducted in 120 NAFLD patients randomly
      assigned to receive 25 MUg calcitriol (n = 37), 500 mg calcium carbonate + 25 MUg
      calcitriol (n = 37), or placebo (n = 36) every day with their lunch meals while
      following a weight-loss program. RESULTS: Weight, BMI and fat mass reduction were
      significant in each group after 12 wk of intervention (p < 0.001), but
      differences among the groups was not significant after 12 wk of the study,
      adjusted to the baseline measurements. Significant reduction in fasting plasma
      glucose (FPG), insulin, insulin resistance (by HOMA-IR) and TG concentrations and
      an increase in HDL.C was seen over the 12 wk of study in each group (p < 0.001).
      Adjusting to the baseline measurements, there was significant difference in FPG
      (p < 0.001), HOMA-IR (p < 0.001), serum insulin (p = 0.01), TG (p = 0.01) and
      HDL.C (p < 0.001) among the groups after 12 wk of the study. The calcium plus
      calcitriol group showed a significant decrease in ALT and FPG and increase in
      HDL.C level compared with the calcitriol group, adjusted to the baseline measures
      (p < 0.001). CONCLUSIONS: Our results suggest that calcium plus calcitriol
      supplementation for 12 weeks may be potentially effective for biochemical
      parameters in NAFLD patients. Further additional larger controlled trials are
      needed to confirm these findings. REGISTRATION: Registered under
      ClinicalTrials.gov Identifier no. IRCT201408312709N29.

PMID- 27720404
TI  - Video Coaching as an Efficient Teaching Method for Surgical Residents-A
      Randomized Controlled Trial.
AB  - BACKGROUND: As surgical training is evolving and operative exposure is
      decreasing, new, effective, and experiential learning methods are needed to
      ensure surgical competency and patient safety. Video coaching is an emerging
      concept in surgery that needs further investigation. DESIGN: In this randomized
      controlled trial conducted at a single teaching hospital, participating residents
      were filmed performing a side-to-side intestinal anastomosis on cadaveric dog
      bowel for baseline assessment. The Surgical Video Coaching (SVC) group then
      participated in a one-on-one video playback coaching and debriefing session with
      a surgeon, during which constructive feedback was given. The control group went
      on with their normal clinical duties without coaching or debriefing. All
      participants were filmed making a second intestinal anastomosis. This was
      compared to their first anastomosis using a 7-category-validated technical skill
      global rating scale, the Objective Structured Assessment of Technical Skills. A
      single independent surgeon who did not participate in coaching or debriefing to
      the SVC group reviewed all videos. A satisfaction survey was then sent to the
      residents in the coaching group. SETTING: Department of Surgery,
      HopitalMaisonneuve-Rosemont, tertiary teaching hospital affiliated to the
      University of Montreal, Canada. PARTICIPANTS: General surgery residents from
      University of Montreal were recruited to take part in this trial. A total of 28
      residents were randomized and completed the study. RESULTS: After intervention,
      the SVC group (n = 14) significantly increased their Objective Structured
      Assessment of Technical Skills score (mean of differences 3.36, [1.09-5.63], p =
      0.007) when compared to the control group (n = 14) (mean of differences 0.29, p =
      0.759). All residents agreed or strongly agreed that video coaching was a time
      efficient teaching method. CONCLUSIONS: Video coaching is an effective and
      efficient teaching intervention to improve surgical residents' technical skills.

PMID- 27720405
TI  - Construct Validity, Assessment of the Learning Curve, and Experience of Using a
      Low-Cost Arthroscopic Surgical Simulator.
AB  - OBJECTIVE: We have developed a low-cost, portable shoulder simulator designed to
      train basic arthroscopic skills. This study aimed to establish the construct
      validity of the simulator by determining which parameters discriminated between
      experience levels and to assess the experience of using the simulator. DESIGN:
      Participants were given an introductory presentation and an untimed practice run
      of a 6-step triangulation task using hooks and rubber bands. A total of 6
      consecutive attempts at the task were timed, and the number of times the
      participant looked at their hands during the task was recorded. Participants then
      completed a questionnaire on their experience of using the simulator. SETTING: St
      George's Hospital, London and the South West London Elective Orthopaedic Centre,
      Surrey. PARTICIPANTS: Medical students, trainee doctors and surgeons, and
      consultant surgeons were approached to use the simulator. Participation was
      voluntary and nonincentivized. In total, 7 orthopedic consultants, 12 trainee
      doctors (ranging from foundation year 1 to clinical fellow post-Certificate of
      Completion of Training), and 9 medical students were recruited. RESULTS: The
      average time for medical students to complete the task was 161 seconds, compared
      to 118 seconds for trainees, and 84 seconds for consultants. The average fastest
      time for medical students was 105 seconds, 73 seconds for trainees, and 52
      seconds for consultants. Students were significantly slower than trainees (p =
      0.026) and consultants (p = 0.001). However, times did not differ significantly
      between trainees and consultants. Consultants looked at their hands 0.7 times on
      average during the task compared with 2.8 and 3.4 times for trainees and
      students, respectively. More than 95% of participants found the exercise
      interesting and agreed or strongly agreed that the simulator was easy to use,
      easily portable, and well designed and constructed. DISCUSSION: This study has
      established construct validity of the simulator by demonstrating the ability to
      distinguish between surgical experience levels. The learning curve shows
      improvement in individuals with or without arthroscopic or surgical experience.
      Simulation is becoming increasingly important in the training of medical students
      and surgical trainees; this study has established that low-cost portable
      arthroscopic box trainers may play a significant role.

PMID- 27720406
TI  - Vesiculobullous Eruption as an Atypical Hand, Foot, and Mouth Presentation.

PMID- 27720407
TI  - The Changing Landscape of Childhood Inflammatory Central Nervous System
      Disorders.

PMID- 27720408
TI  - Ductus Arteriosus Aneurysm Thrombosis with Mass Effect Causing Pulmonary
      Hypertension in the First Week of Life.

PMID- 27720410
TI  - A Data Entry System for Dietary Surveys Based on Visual Basic for Applications
      Programming.

PMID- 27720409
TI  - Fourth-Grade Children's Reporting Accuracy for Amounts Eaten at School-Provided
      Meals: Insight from a Reporting-Error-Sensitive Analytic Approach Applied to
      Validation Study Data.
AB  - BACKGROUND: Validation studies that have directly assessed reporting accuracy for
      amounts eaten have provided results in various ways. OBJECTIVE: To analyze amount
      categories of a reporting-error-sensitive approach for insight concerning
      reporting accuracy for amounts eaten. DESIGN: For a cross-sectional validation
      study, children were observed eating school-provided breakfast and lunch, and
      randomized to one of eight 24-hour recall conditions (two retention intervals
      [short and long] crossed with four prompts [forward, meal name, open, and
      reverse]). PARTICIPANTS/SETTING: Data collected during 3 school years (2011-2012
      to 2013-2014) on 455 children from 10 schools (four districts) in a southern US
      state. MAIN OUTCOME MEASURES: Items were classified as matches (observed and
      reported), omissions (observed but unreported), or intrusions (unobserved but
      reported). Within amount categories (matches [corresponding, overreported, and
      underreported], intrusions [overreported], and omissions [underreported]), item
      amounts were converted to kilocalories. STATISTICAL ANALYSES PERFORMED: A
      multilevel model was fit with food-level explanatory variables (amount category
      and meal) and child-level explanatory variables (retention interval, prompt, sex,
      and race/ethnicity). To investigate inaccuracy differences, t tests on three
      contrasts were performed. RESULTS: Inaccuracy differed by amount category
      (P<0.001; in order from largest to smallest: omission, intrusion, underreported
      match, and overreported match), meal (P=0.01; larger for breakfast), retention
      interval (P=0.003; larger for long), sex (P=0.004; larger for boys),
      race/ethnicity (P=0.045; largest for non-Hispanic whites), and amount
      category*meal interaction (P=0.046). Overreported amounts were larger for
      intrusions than overreported matches (P<0.0001). Underreported amounts were
      larger for omissions than underreported matches (P<0.0001). Overall underreported
      amounts (from omissions and underreported matches) exceeded overall overreported
      amounts (from intrusions and overreported matches) (P<0.003). CONCLUSIONS: Amount
      categories provide a standard way to analyze validation study data on reporting
      accuracy for amounts eaten, and compare results across studies. Multilevel
      analytic models reflecting the data structure are recommended for inference. To
      enhance reporting accuracy for amounts eaten, focus on increasing reports of
      correct items, thereby yielding more matches with fewer intrusions and omissions.

PMID- 27720411
TI  - Hyponatremia as presentation in a patient with neurosarcoidosis.
AB  - Sarcoidosis is an inflammatory disease with unknown cause characterized by non
      caseating granuloma formations. It may present with bilateral hilar
      lymphadenopathy, skin lesions, eye and musculoskeletal system involvement.
      Hypercalcemia and hypercalciuria are important electrolyte imbalances resulting
      from sarcoidosis and sometimes they may cause nephrolitiasis and kidney failure.
      Hyponatremia, although being quite rare, has been found in some patients with
      sarcoidosis. Herein, we have reported a patient with neurosarcoidosis who
      presented with hyponatremia and responded well to corticosteroid treatment.

PMID- 27720412
TI  - Suture spanning augmentation of single-row rotator cuff repair: a biomechanical
      analysis.
AB  - BACKGROUND: This in vitro study evaluated the biomechanical benefit of adding
      spanning sutures to single-row rotator cuff repair. METHODS: Mechanical testing
      was performed to evaluate 9 pairs of cadaveric shoulders with complete rotator
      cuff repairs, with a single-row technique used on one side and the suture
      spanning technique on the other. The spanning technique included sutures from 2
      lateral anchors securing tendon near the musculotendinous junction, spanning the
      same anchor placement from single-row repair. The supraspinatus muscle was loaded
      to 100 N at 0.25 Hz for 100 cycles, followed by a ramp to failure. Markers and a
      video tracking system measured anterior and posterior gap formation across the
      repair at 25-cycle intervals. The force at which the stiffness decreased by 50%
      and 75% was determined. Data were compared using paired t-tests. RESULTS: One
      single-row repair failed at <25 cycles. Both anterior and posterior gap distances
      tended to be 1 to 2 mm larger for the single-row repairs than for the suture
      spanning technique. The difference was statistically significant at all cycles
      for the posterior gap formation (P <= .02). The trends were not significant for
      the anterior gap (P >= .13). The loads at which the stiffness decreased by 50%
      and 75% did not differ significantly between the 2 types of repair (P >= .10).
      CONCLUSIONS: The suture spanning technique primarily improved posterior gap
      formation. Decreased posterior gap formation could reduce failure rates for
      rotator cuff repair.

PMID- 27720413
TI  - Neer Award 2015: Analysis of cytokine profiles in the diagnosis of periprosthetic
      joint infections of the shoulder.
AB  - BACKGROUND: Periprosthetic joint infection (PJI) after shoulder arthroplasty can
      present a diagnostic and therapeutic challenge. This study evaluated the
      diagnostic utility of broader synovial fluid cytokine analysis for identifying
      PJI in patients undergoing revision shoulder arthroplasty. METHODS: Synovial
      fluid levels of 9 cytokines (interleukin [IL] 6, granulocyte-macrophage colony
      stimulating factor, IL-1beta, IL-12, IL-2, IL-8, interferon-gamma, IL-10, and
      tumor necrosis factor-alpha) were measured in 75 cases of revision shoulder
      arthroplasty with a multiplex immunoassay. Cases were classified into infection
      categories and groups based on objective perioperative findings. Differences in
      cytokine levels among infection groups were evaluated. Receiver operating
      characteristic curves were used to assess the diagnostic utility of the
      individual synovial fluid cytokines and combinations of cytokines in determining
      infection status. RESULTS: Synovial IL-6, granulocyte-macrophage colony
      stimulating factor, interferon-gamma, IL-1beta, IL-2, IL-8, and IL-10 were
      significantly elevated in cases of revision shoulder arthroplasty classified as
      infected. Individually, IL-6, IL-1beta, IL-8, and IL-10 showed the best
      combination of sensitivity and specificity for predicting infection, and a
      combined cytokine model consisting of IL-6, tumor necrosis factor-alpha, and IL-2
      showed better diagnostic test characteristics than any cytokine alone, with
      sensitivity of 0.80, specificity of 0.93,, positive and negative predictive
      values of 0.87 and 0.89, and positive and negative likelihood ratios of 12.0 and
      0.21. CONCLUSIONS: Individual and combined synovial fluid cytokine analysis were
      both more effective than routine perioperative testing, such as serum erythrocyte
      sedimentation rate and C-reactive protein, in the diagnosis of PJI of the
      shoulder. Once validated, combined synovial fluid cytokine analysis could be used
      as a predictive tool to determine the probability of PJI in patients undergoing
      revision shoulder arthroplasty and better guide treatment.

PMID- 27720414
TI  - Rotator cuff surgery in patients older than 75 years with large and massive
      tears.
AB  - BACKGROUND: The purpose of this study was to evaluate whether rotator cuff repair
      improves subjective and functional outcomes in patients aged >=75 years. METHODS:
      From May 2005 to March 2013, 121 elderly patients who underwent rotator cuff
      repair for large and massive rotator cuff tears were evaluated retrospectively.
      Patients with an American Society of Anesthesiologists physical status
      classification system grade >=4 were excluded. The patients were evaluated using
      visual analog scales, subjective satisfaction surveys, American Shoulder and
      Elbow Surgeons scores, and Constant scores. The Katz index of activity of daily
      living (ADL) and functional independence measure motor score were used to
      evaluate ADLs. Postoperative magnetic resonance imaging (MRI) was performed to
      investigate the structural integrity of repaired cuffs. RESULTS: In total, 64
      patients were enrolled in the study; 80% were satisfied with their results.
      Visual analog scale scores improved from 6.4 to 2.3, American Shoulder and Elbow
      Surgeons scores from 42 to 84, and Constant scores from 42 to 76. Katz ADL scores
      improved from 3.4 to 5.0. Functional independence measure motor score improved
      from 22 to 51. Of the 64 patients, 46 underwent MRI 1 year postoperatively.
      Follow-up MRI revealed retears in 26% of patients. All patients with retears had
      improved subjective outcomes and functional scores. No patients died or
      experienced complications requiring intensive care or extended hospitalization.
      CONCLUSIONS: Surgical treatment for large to massive rotator cuff tears in
      elderly patients with American Society of Anesthesiologists grade <4 provides
      good functional outcomes without morbidity, even in those with retears.

PMID- 27720415
TI  - Subscapularis tendon loading during activities of daily living.
AB  - BACKGROUND: The purpose of this study was to determine the relative amount of
      load that is transmitted through the superior portion of the subscapularis during
      activities of daily living as compared with the load that is transmitted through
      the middle and inferior portions in a normal shoulder and in a shoulder with a
      supraspinatus tear. METHODS: By use of the Newcastle shoulder model, the
      subscapularis was modeled with 3 lines of action encircling the humeral head. The
      load was measured in the entire subscapularis, and the percentage of this load in
      each of the 3 tendinous bands was calculated. Subsequently, a supraspinatus tear
      was simulated, and the forces generated by the subscapularis and glenohumeral
      joint contact forces were measured. RESULTS: The maximum force produced by the
      entire subscapularis muscle for the various activities ranged from 3 to 43 N.
      Load sharing between the 3 subscapularis bands showed that the superior band bore
      the largest percentage of the total load of the muscle (95% +/- 2%). The load in
      the subscapularis, particularly in the superior band, increased significantly
      when a supraspinatus tear was simulated (P < .0001). CONCLUSION: The superior
      band of the subscapularis tendon bears the highest percentage of load compared
      with the middle or inferior band. The load in the subscapularis increased
      significantly in the presence of a simulated supraspinatus tear. Because a
      disproportionate amount of force is transmitted through the superior
      subscapularis, more clinical research is warranted to determine whether tears in
      this region should be routinely repaired.

PMID- 27720416
TI  - Safety and Effectiveness of Percutaneous Closure of Left Atrial Appendage in
      Patients With Intracranial Hemorrhage.

PMID- 27720417
TI  - Maintaining a clinical weight loss after intensive lifestyle intervention is the
      key to cardiometabolic health.
AB  - OBJECTIVE: Intensive lifestyle interventions (ILI) are criticised for ineffective
      obesity treatment because weight loss over time is modest and thus of limited
      clinical relevance. However, a subgroup (5-30%) maintains a clinical weight loss
      >10%, but it is not clear if cardiometabolic health follows this pattern. The aim
      was to study the effect of different magnitudes of weight loss maintenance after
      ILI on cardiometabolic health. METHODS: Eighty out of 2420 former participants
      (age: 36+/-1, BMI: 38+/-1, (means +/-SE)) in an 11-12-week ILI were recruited
      into 3 groups; clinical weight loss maintenance (>10% weight loss), moderate
      maintenance (1-10%), and weight regain based on weight loss at follow-up (5.3+/
      0.4years). Weight loss during the ILI was achieved by increased physical activity
      and hypo-caloric diet. Dual X-ray Absorptiometry, blood sample, skeletal muscle
      biopsy and VO2max test were used to determine cardiometabolic health at follow
      up. RESULTS: At follow-up, the clinical weight loss maintenance group scored
      better in the following variables compared to the other groups: BMI (31+/-1, 33+/
      2, 43+/-2kg/m2), composition (34+/-2, 40+/-1, 49+/-1% fat), visceral adipose
      tissue (0.8+/-0.2, 1.7+/-0.5, 2.4+/-0.4kg), plasma triglycerides (0.8+/-0.2,
      1.3+/-0.4, 1.6+/-0.3mmol/L), plasma glucose (4.9+/-0.1, 5.9+/-0.4, 5.9+/
      0.1mmol/L), Hb1Ac (5.1+/-0.0, 5.6+/-0.2, 5.8+/-0.2%), protein content in skeletal
      muscle of GLUT4 (1.5+/-0.2, 0.9+/-0.1, 1.0+/-0.1 AU) and hexokinase II (1.6+/
      0.2, 1.0+/-0.2, 0.7+/-0.1 AU), citrate synthase activity (155+/-6, 130+/-5, 113+/
      5MUmol/g/min) and VO2max (49+/-1, 43+/-1, 41+/-1mL/min/FFM) (p<0.05). CONCLUSION:
      Cardiometabolic health is better in participants who have maintained >10% weight
      loss compared to moderate weight loss and weight regain.

PMID- 27720419
TI  - Letter to the editor on innovative metabolic operations.

PMID- 27720418
TI  - A comparative study of the metabolic effects of LSG and LRYGB in Chinese diabetes
      patients with BMI<35 kg/m2.
AB  - BACKGROUND: The metabolic effects of laparoscopic sleeve gastrectomy (LSG) and
      laparoscopic Roux-en-Y gastric bypass (LRYGB) in type 2 diabetes (T2D) patients
      who do not meet National Institutes of Health indications has not been well
      studied. OBJECTIVES: To compare the effectiveness of LSG and LRYGB in Chinese T2D
      patients with body mass index (BMI)<35 kg/m2. SETTING: University hospital,
      China. METHODS: A nonrandomized cohort of patients who underwent LRYGB (n = 64)
      and LSG (n = 19) were followed up for 3 years and the outcomes (weight loss and
      remission of diabetes and other metabolic parameters) were compared. Univariate
      and multivariate analyses were applied to find associated parameters of T2D
      remission. RESULTS: In total, 5 patients (6%) were lost to follow-up. No
      significant differences in mean percentage of excess weight loss and BMI were
      observed between the 2 groups at 2 years. At 3-year follow-up, the LRYGB group
      had significantly higher percentage of excess weight loss and lower BMI. The
      total (complete and partial) remission rate achieved with both bariatric
      procedures was 75.9% at 1 year and 56.4% at 3 years. Surgical safety, diabetes
      remission, and remission of other obesity-related co-morbidities were comparable
      between the 2 groups. Patients who achieved complete or partial remission had
      lower fasting plasma glucose, lower plasma glucose at 2 hours, lower glycated
      hemoglobin, and higher fasting C peptide than the other patients at baseline.
      High recurrence rates of hypertension and hyperuricemia were observed at 3 years
      postoperation. CONCLUSIONS: Both LSG and LRYGB are safe and effective bariatric
      procedures for T2D in this Chinese population with diabetes and BMI<35 kg/m2.

PMID- 27720420
TI  - Perioperative thromboprophylaxis in severely obese patients undergoing bariatric
      surgery: insights from a French national survey.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death in obese
      patients undergoing bariatric surgery (BS), but there is neither consensus nor
      high-level guidelines yet on VTE prophylaxis in this specific population.
      OBJECTIVE: We aimed to evaluate patterns of BS perioperative thromboprophylaxis
      practices. SETTING: French obesity specialized care centers (CSO), which are
      tertiary care referral hospitals for the most severe cases of obesity METHODS: A
      detailed questionnaire survey (11 opened, 15 closed questions) investigating
      their prophylactic schemes of anticoagulation (molecule, dose, weight-adjustment,
      duration, associated measures, follow-up) was sent to the 37 CSO. RESULTS:
      Completion rate was 92%. Over 90% of respondents indicated using low molecular
      weight heparin. Enoxaparin was the most commonly used molecule (89%), twice daily
      (71%), started mostly 6 hours after BS (74%), whereas fondaparinux (9%),
      dalteparin (6%), and tinzaparin (6%) were less often prescribed. Dosing varied
      significantly according to centers from 4000 to 12,000 IU/d, with the most
      commonly used dose being 8000 IU once daily, 83%, as well as treatment duration
      (1 week, 9%; 3 weeks, 47%). Half CSO adjusted low molecular weight heparin dose
      to weight. Biological monitoring was performed in 88%. Only 1 center followed
      systematically anti-Xa activity. Associated measures such as elastic stoking or
      intermittent pneumatic compression were used in 32% and 26%, respectively, and
      both were used in 39%. CONCLUSION: This study finds significant discrepancies in
      thromboprophylaxis practices in obese patients undergoing BS, particularly with
      respect to treatment duration and dose adjustment, highlighting the urgent need
      for improved implementation of existing clinical practice guidelines in this VTE
      high-risk population.

PMID- 27720421
TI  - Experimental evaluation of chromatographic performance of capillary and
      microfluidic columns with linear or curved channels.
AB  - We prepared 0.3 or 0.15mm i.d. columns from both fused silica capillaries and
      planar titanium wafers with machined grooves. Both types of devices were packed
      with sub-two micron C18 sorbent. Chromatographic efficiency and peak capacity
      were tested using LC instruments with low extra column dispersion (300nL2 or
      30nL2 for 0.3 or 0.15mm i.d. columns, respectively). Micro column testing in
      gradient mode was less affected by extra column (pre-column) dispersion. To
      exploit this feature we developed a method for estimation of column efficiency
      from gradient analysis using the theoretical relationship (Pc-1)=N0.5*const. The
      validity of this relationship was experimentally verified using 2.1mm i.d. and
      0.3mm i.d. columns. The (Pc-1) versus N relationship was experimentally
      determined with straight columns, which in turn was employed for the estimation
      of microfluidic column efficiency. Microfluidic devices with serpentine channels
      exhibited lower isocratic efficiency than straight capillary columns, but the
      loss of peak capacity was less significant. The loss chromatographic efficiency
      due to zone dispersion in serpentine microfluidic channels was more apparent for
      0.3 than 0.15mm i.d. devices. Gradient performance of 0.15*100mm microfluidic
      columns was comparable to state-of-the-art 2.1*100mm columns packed with the same
      sorbent.

PMID- 27720422
TI  - Hollow molecular imprinted polymers towards rapid, effective and selective
      extraction of caffeic acid from fruits.
AB  - Rapid and selective extraction and enrichment of trace bioactive analytes from
      complex matrices were of significant importance for efficient and accurate
      quantification. Here, novel hollow molecular imprinted polymers (HMIPs) were
      prepared using caffeic acid (CA) as template, 4-vinylpyridine (4-VP) as
      functional monomer, and Fe3O4@SiO2 as sacrificial support. Fourier transform
      infrared spectrometer (FT-IR), transmission electron microscopy (TEM), nitrogen
      adsorption and thermo-gravimetric analysis (TGA) were used to verify the
      successful synthesis of HMIPs. Hollow structure with large surface area
      (325.8m2/g) made most recognition sites locate on the surface of HMIPs, resulting
      in high binding capacity (21.10mg/g) and fast kinetic binding (35min) in
      comparison with magnetic MIPs (MMIPs) and solid MIPs. The equilibrium data fitted
      well to Freundlich equation and the adsorption process could be described by
      pseudo-second order model. The selectivity performance of HMIPs was favorable.
      Finally, HMIPs were successfully used as adsorbent to rapidly and selectively
      extract and enrich CA from fruits with a relatively satisfactory recovery (85.6
      103.5%). Coupling with high-performance liquid chromatography (HPLC), the content
      of CA in four kinds of fruits (kiwifruit, apple, papaya and waxberry) was
      determined as less than 1.0MUg/g fresh fruit. Results indicated the superiority
      of HMIPs in the selective extraction of target compound from complex matrices.

PMID- 27720423
TI  - Filler characteristics of modern dental resin composites and their influence on
      physico-mechanical properties.
AB  - OBJECTIVE: The mechanical properties of dental resin-based composites (RBCs) are
      highly dependent on filler characteristics (size, content, geometry,
      composition). Most current commercial materials are marketed as "nanohybrids"
      (i.e. filler size <1MUm). In the present study, filler characteristics of a
      selection of RBCs were described, aiming at identifying correlations with physico
      mechanical properties and testing the relevance of the current classification.
      METHODS: Micron/sub-micron particles (> or <500nm) were isolated from 17
      commercial RBCs and analyzed by laser diffractrometry and/or electron microscopy.
      Filler and silane content were evaluated by thermogravimetric analysis and a
      sedimentation technique. The flexural modulus (Eflex) and strength (sigmaflex)
      and micro-hardness were determined by three-point bending or with a Vickers
      indenter, respectively. Sorption was also determined. All experiments were
      carried out after one week of incubation in water or 75/25 ethanol/water.
      RESULTS: Average size for micron-sized fillers was almost always higher than
      1MUm. Ranges for mechanical properties were: 3.7<Eflexwater<16.3GPa,
      86<sigmaflexwater<161MPa and 23.7<hardnesswater<108.3HV0.2/30. Values generally
      decreased after storage in ethanol/water (Deltamax=86%). High inorganic filler
      contents (>75wt%) were associated with the highest mechanical properties (Eflex
      and sigmaflex>12GPa and 130MPa, respectively) and lowest solvent sorption
      (~0.3%). SIGNIFICANCE: Mechanical properties and filler characteristics
      significantly vary among modern RBCs and the current classification does not
      accurately illustrate either. Further, the chemical stability of RBCs differed,
      highlighting differences in resin and silane composition. Since Eflex and
      sorption were well correlated to the filler content, a simple and unambiguous
      classification based on such characteristic is suggested, with three levels
      (ultra-low fill, low-fill and compact resin composites).

PMID- 27720424
TI  - The network substrate of confabulatory tendencies in Alzheimer's disease.
AB  - Confabulatory phenomena are rare in the early stage of Alzheimer's disease (AD),
      are often provoked and are triggered by questions or in response to
      neuropsychological testing. In this retrospective study functional connectivity
      alterations were investigated for the first time in a group of patients with
      early AD who had shown evidence of verbal and non-verbal confabulatory
      tendencies. Resting-state functional magnetic resonance imaging (fMRI) scans of
      18 confabulating patients were compared with those of 18 non confabulators. The
      finding showed that confabulators had decreased connectivity between a seed
      region in the right inferolateral frontal cortex and right mediotemporal and
      insular regions, and increased connectivity with frontal areas and a homologous
      region on the left. The seed control region in the left inferolateral frontal
      cortex showed increased connectivity with midline frontal and anterior cingulate
      regions, while a decrease was found in temporal areas. Confabulatory tendencies
      appear in early AD as a result of disconnection between crucial computational
      hubs in frontal and mediotemporal regions. This disconnection is coupled with the
      presence of up-regulation of frontal activity, and especially of midline and
      anterior cingulate regions, which might disrupt efficient output monitoring in
      confabulators.

PMID- 27720425
TI  - Sperm head shaping in ratites: New insights, yet more questions.
AB  - Head shaping in mammalian sperm is regulated by a number of factors including
      acrosome formation, nuclear condensation and the action of the microtubular
      manchette. A role has also been suggested for the attendant Sertoli cells and the
      perinuclear theca (PT). In comparison, relatively little information is available
      on this topic in birds and the presence of a PT per se has not been described in
      this vertebrate order. This study revealed that a similar combination of factors
      contributed to head shaping in the ostrich, emu and rhea, although the Sertoli
      cells seem to play a limited role in ratites. A fibro-granular structure
      analogous to the mammalian PT was identified, consisting of sub- and post
      acrosomal components. The latter was characterized by stage-specific finger-like
      projections that appeared to emanate from the cytoplasmic face of the nuclear
      envelope. They were particularly obvious beneath the base of the acrosome, and
      closely aligned, but not connected to, the manchette microtubules. During the
      final stages of chromatin condensation and elongation of the sperm head the
      projections abruptly disappeared. They appear to play a role in stabilizing the
      shape of the sperm head during the caudal translocation of the spermatid
      cytoplasm.

PMID- 27720426
TI  - Rho GTPases operating at the Golgi complex: Implications for membrane traffic and
      cancer biology.
AB  - The Golgi complex is the central unit of the secretory pathway, modifying,
      processing and sorting proteins and lipids to their correct cellular
      localisation. Changes to proteins at the Golgi complex can have deleterious
      effects on the function of this organelle, impeding trafficking routes through
      it, potentially resulting in disease. It is emerging that several Rho GTPase
      proteins, namely Cdc42, RhoBTB3, RhoA and RhoD are at least in part localised to
      the Golgi complex, and a number of studies have shown that dysregulation of their
      levels or activity can be associated with cellular changes which ultimately drive
      cancer progression. In this mini-review we highlight some of the recent work that
      explores links between form and function of the Golgi complex, Rho GTPases and
      cancer.

PMID- 27720427
TI  - Using trip diaries to mitigate route risk and risky driving behavior among older
      drivers.
AB  - To reduce exposure to risky and challenging driving situations and prolong
      mobility and independence, older drivers self-regulate their driving behavior.
      But self-regulation can be challenging because it depends on drivers' ability to
      assess their limitations. Studies using self-reports, survey data, and hazard and
      risk perception tests have shown that driving behavior feedback can help older
      drivers assess their limitations and adjust their driving behavior. But only
      limited work has been conducted in developing feedback technology interventions
      tailored to meet the information needs of older drivers, and the impact these
      interventions have in helping older drivers self-monitor their driving behavior
      and risk outcomes. The vehicles of 33 drivers 65 years and older were
      instrumented with OBD2 devices. Older drivers were provided access to customized
      web-based Trip Diaries that delivered post-trip feedback of the routes driven,
      low-risk route alternatives, and frequency of their risky driving behaviors. Data
      were recorded over four months, with baseline driving behavior collected for one
      month. Generalized linear mixed effects regression models assessed the effects of
      post-trip feedback on the route risk and driving behaviors of older drivers.
      Results showed that post-trip feedback reduced the estimated route risk of older
      drivers by 2.9% per week, and reduced their speeding frequency on average by 0.9%
      per week. Overall, the Trip Diary feedback reduced the expected crash rate from 1
      in 6172 trips to 1 in 7173 trips, and the expected speeding frequency from 46% to
      39%. Thus providing older drivers with tailored feedback of their driving
      behavior and crash risk could help them appropriately self-regulate their driving
      behavior, and improve their crash risk outcomes.

PMID- 27720428
TI  - Letter: Commentary on Breathnach et al.

PMID- 27720429
TI  - Response to Jamieson's and Bader's comments on Breathnach et al. Probability of
      detection of DNA deposited by habitual wearer and/or the second individual who
      touched the garment.

PMID- 27720430
TI  - The role of splenectomy before liver transplantation in biliary atresia patients.
AB  - BACKGROUND/PURPOSE: There is currently no unified view regarding whether liver
      transplantation or splenectomy should be performed for hypersplenism before liver
      transplantation in biliary atresia (BA) patients. We herein describe the efficacy
      of splenectomy before liver transplantation. METHODS: Splenectomy was performed
      in ten patients with hypersplenism associated with BA. We retrospectively
      reviewed their perioperative and postoperative courses, the number of leukocytes
      and thrombocytes, and the MELD score. RESULTS: The mean age was 17.5+/-7.0years
      (range 11-31years), and the male-to-female ratio was 1:1. The platelet and
      leukocyte levels increased after splenectomy and returned to normal levels one
      month postoperatively. The mean MELD score after splenectomy was significantly
      decreased after splenectomy: 10+/-2.1 vs 7.6+/-1.8. In particular, PT-INR
      improved. Five patients underwent liver transplantation because of
      hepatopulmonary syndrome and repeated bouts of cholangitis, whereas the remaining
      five patients did not undergo liver transplantation because of improvements in
      the liver function (the mean follow-up period was 56months). The postoperative
      complications included portal vein thrombosis and intestinal perforation, but the
      patient survival rates remained at 100%. CONCLUSION: After splenectomy, both
      pancytopenia and the liver function clearly improved. Splenectomy should
      therefore be a treatment option for patients with hypersplenism before liver
      transplantation. LEVEL OF EVIDENCE: Retrospective Comparative Study - Level III.

PMID- 27720431
TI  - [Common physiological basis for post-traumatic stress disorder and dependence to
      drugs of abuse: Implications for new therapeutic approaches].
AB  - Post-traumatic stress disorder (PTSD) and addiction to drugs of abuse are two
      common diseases, showing high comorbidity rates. This review presents a number of
      evidence showing similarities between these two pathologies, especially the hyper
      responsiveness to environmental cues inducing a reactivation of the target memory
      leading either to re-experiencing (PTSD), or drug craving. Accordingly, PTSD and
      addiction to drug of abuse might by considered as memory pathologies, underlined
      by the same physiological process. We propose that these two pathologies rely on
      an uncoupling of the monoaminergic systems. According to this hypothesis,
      exposure to extreme conditions, either negative (trauma) or positive (drugs)
      induced a loss of the reciprocal control that one system usually exerts on the
      other monoaminergic system, resulting to an uncoupling between the noradrenergic
      and the serotonergic systems. Results obtained in our laboratory, using animal
      models of these pathologies, demonstrate that after a trauma, such as after
      repeated drug injections, rats developed both a behavioral sensitization
      (increases of the locomotion in response to a stimulation of the monoaminergic
      systems) and a pharmacological sensitization (increases of noradrenergic release
      within the prefrontal cortex). These results support our hypothesis and led us to
      propose new and innovative therapeutic approaches consisting either to induce a
      re-coupling of the monoaminergic systems, or to modify the pathological memories
      by using an emotional memory remodeling. Extremely encouraging results have
      already been obtained in rats and in humans, opening new and promising
      therapeutic avenues.

PMID- 27720432
TI  - Multidetector Computed Tomographic Angiography Imaging of Congenital Pulmonary
      Venous Anomalies: A Pictorial Review.
AB  - Congenital pulmonary venous anomalies are not uncommon that can occur either in
      isolation or in association with different forms of congenital heart disease.
      Clinical presentation of these anomalies may vary from the relatively benign
      single anomalous partial pulmonary venous return to life-threatening critical
      obstructed total anomalous pulmonary venous return. Accurate delineation of these
      anomalies and accompanied cardiovascular anomalies are crucial to guide decision
      making in these patients. Low-dose high-pitch dual-source 256-detector
      multidetector computed tomographic angiography is a fast and reliable imaging
      modality allowing comprehensive noninvasive anatomic imaging in neonates and
      children with congenital pulmonary venous anomalies with lower radiation doses
      and should be preferred for these patients after transthoracic echocardiography.

PMID- 27720433
TI  - Autumnalamide targeted proteins of the immunophilin family.
AB  - Previous works with autumnalamide reported that Store Operated Calcium (SOC)
      channels were blocked through mitochondrial modulation. In the present paper we
      studied the effect of autumnalamide on ionomycin Ca2+ fluxes. Thus, autumnalamide
      did not modify ionomycin-sensitive intracellular pools while the ionomycin
      induced Ca2+ influx was blocked with similar potency whether the incubation was
      done before or after ionomycin-sensitive pools depletion. Nevertheless,
      autumnalamide was not able to inhibit ionomycin-induced Ca2+ influx once the
      membrane channels were activated. Moreover, the compound efficiently inhibited
      flufenamic acid (FFA) Ca2+ release induced in this organelle but no the next
      influx. Since in previous work the effect of autumnalamide was inhibited by
      cyclosporine A (CsA), structures that target this drug were studied. Therefore,
      the affinity of autumnalamide for cyclophilin D (Cyp D) was examined. The KD
      obtained for Cyp D- autumnalamide was 1.51+/-1.399. Moreover, the KD for Cyp A-
      autumnalamide was calculated. The peptide had a similar order of Cyp A binding
      affinity than CsA (8.08+/-1.23 and 6.85+/-1.1MUM respectively). After testing
      autumnalamide-binding capacity for Cyp A, the activity of this compound on Cyp A
      pathway was tested. Thus, the effect on interleukin (IL)-2 release on activated T
      lymphocytes was checked. Autumnalamide was able to reduce IL-2 levels near to T
      cells in resting conditions. Next, the effect over calcineurin and NFATc1 was
      also evaluated. While CsA inhibits both calcineurin and NFATc1, autumnalamide did
      not produce any effect. From these results we can conclude that, autumnalamide
      targeted mitochondrion and prevent T-cells from IL-2 production through the
      modulation of SOC Ca2+ channels.

PMID- 27720435
TI  - Toxic aromatic compounds from fruits of Narthecium ossifragum L.
AB  - The intake of Narthecium ossifragum, commonly known as bog asphodel, has been
      associated with toxic effects observed in sheep for centuries. Although the plant
      has been studied for five centuries little is known about its chemical
      constituents. Six previously undescribed natural products, naringenin(3 ->
      6")luteolin, naringenin(3 -> 6")chrysoeriol, liovil 4-O-beta-glucopyranoside, 2,6
      dimethoxy cinnamic acid, (E)-4-(3-hydroxy-2,2-dimethylchroman-6-yl)but-3-en-2-one
      and (E)-4-(4-(((E)-4-hydroxy-3-methylbut-2-en-1-yl)oxy)phenyl)but-3-en-2-one,
      have been identified from fruits of N. ossifragum for the first time. In
      addition, the rare natural product 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde
      and the five known compounds 4-hydroxycinnamic acid, quercetin 3,3'-dimethyl
      ether, quercetin 3,7-dimethyl ether, chrysoeriol 7-O-beta-glucopyranoside and the
      di-C-glycosylflavone isoschaftoside were all characterized for the first time
      from the fruits of N. ossifragum. The discovery of sufficient amounts of 4
      hydroxy-3-(3-methylbut-2-enyl)benzaldehyde in fresh plant material of N.
      ossifragum to allow complete structure elucidation by NMR and HRMS supports the
      possibility that fungi associated with N. ossifragum may be able to produce
      enough toxins to play a significant role in the pathogenicity of N. ossifragum. 4
      Hydroxy-3-(3-methylbut-2-enyl)benzaldehyde showed mild toxicity towards normal
      rat kidney (NRK) and more profound activity towards MOLM13 acute myeloid leukemia
      cells (IC50 = 430 MUM and 68 MUM, respectively). Naringenin(3 -> 6")luteolin had
      IC50 of 230 MUM towards NRK cells, and 115 MUM towards MOLM13 cells. Microscopic
      evaluation suggests that these two compounds induce cell death by different
      mechanisms.

PMID- 27720438
TI  - Surgery for postinfarction ventricular septal rupture.

PMID- 27720437
TI  - Sci-Hub & ethical issues.

PMID- 27720434
TI  - Pneumocystis infection alters the activation state of pulmonary macrophages.
AB  - Recent studies show a substantial incidence of Pneumocystis jirovecii
      colonization and infection in patients with chronic inflammatory lung conditions.
      However, little is known about the impact of Pneumocystis upon the regulation of
      pulmonary immunity. We demonstrate here that Pneumocystis polarizes macrophages
      towards an alternatively activated macrophage-like phenotype. Genetically
      engineered mice that lack the ability to signal through IL-4 and IL-13 were used
      to show that Pneumocystis alternative macrophage activation is dependent upon
      signaling through these cytokines. To determine whether Pneumocystis-induced
      macrophage polarization would impact subsequent immune responses, we infected
      mice with Pneumocystis and then challenged them with Pseudomonas aeruginosa 14
      days later. In co-infected animals, a higher proportion of macrophages in the
      alveolar and interstitial spaces expressed both classical and alternatively
      activated markers and produced the regulatory cytokines TGFbeta and IL-10, as
      well as higher arginase levels than in mice infected with P. aeruginosa alone.
      Our results suggest that Pneumocystis reprograms the overall macrophage
      repertoire in the lung to that of a more alternatively-activated setpoint,
      thereby altering subsequent immune responses. These data may help to explain the
      association between Pneumocystis infection and decline in pulmonary function.

PMID- 27720436
TI  - Supply chain management of health commodities for reducing global disease burden.
AB  - PURPOSE: Reducing global disease burden requires improving access to medicines,
      thus the need for efficient and effective supply chain management for medicines.
      The Nigerian government came up with new policies on Mega Drug Distribution
      Centres and National Drug Distribution Guidelines to improve access to quality
      medicines with pharmacists having a key role to play. However, pharmacists in
      Nigeria seem not to be aware and adequately equipped to handle the medicines
      supply chain. This article aimed at assessing the awareness and readiness of
      Nigerian pharmacists on supply chain management practices for improving access to
      medicines. METHODS: Pharmacists in Nigeria's Capital were randomly sampled. Semi
      structured questionnaires were administered. Descriptive statistics was used in
      data analysis. P values less than 0.05 were considered to be significant.
      RESULTS: 29.3%, 20.7% and 53.7% were not aware of supply chain management,
      National Drug Distribution Guidelines and Mega Drug Distribution Centres,
      respectively. 85.46% do not have a copy of the National Drug Distribution
      Guidelines. 78% were not aware that Mega Drug Distribution Centres are already
      operational. 35.4% have never been involved in any supply chain management
      practice. 69.5% often experience stock out of vital and essential medicines, of
      which 85.2% were in hospitals. 15.9% were successful in managing their facility's
      supply chains. 84.1% opined that pharmacists in Nigeria are not yet ready to
      handle the medicines supply chain. CONCLUSIONS: Findings showed limited awareness
      and readiness on supply chain management of medicines. This may be due to
      inadequate supply chain management skills and infrastructure, poor financing,
      lack of accountability and poor management. Tackling these as well as pharmacists
      showing more interest in the country's health policies and obtaining necessary
      postgraduate certifications will lead to improvements. This will improve access
      to quality medicines and thus help in the fight to reduce disease burden both
      locally and globally.

PMID- 27720439
TI  - Etiology of Heart Failure and Outcomes in Patients Hospitalized for Acute
      Decompensated Heart Failure With Preserved or Reduced Ejection Fraction.
AB  - In the setting of acute decompensated heart failure (HF), relations among the
      etiology of HF, left ventricular systolic function, and outcomes are unclear. The
      aim of this study was to investigate the association of HF etiology with outcomes
      in patients with acute decompensated HF with a preserved or reduced ejection
      fraction (EF). Of the 4,842 patients enrolled in the Acute Decompensated Heart
      Failure Syndromes registry, 3,810 patients (1,601 with a preserved EF and 2,209
      with a reduced EF) who had a hypertensive, ischemic, valvular, or idiopathic
      dilated etiology of HF were investigated to assess the association of etiology
      with a composite end point (all-cause mortality and readmission for HF). The
      median follow-up period after admission was 502 (381 to 759) days. The composite
      end point was reached in 44.6% and 41.7% of the preserved and reduced EF groups,
      respectively. After adjustment for multiple co-morbidities, the risk of the
      composite end point was comparable among hypertensive, ischemic, and valvular
      etiologies in the preserved EF group. In contrast, in the reduced EF group,
      ischemic etiology was associated with a tendency toward greater risk of the
      composite end point than hypertensive etiology (but this difference was not
      significant), whereas valvular etiology was associated with a significantly
      greater risk of the composite end point relative to hypertensive or idiopathic
      dilated etiology. In conclusion, this study demonstrated that taking the etiology
      of HF into account may help to reduce the heterogeneity of acute decompensated HF
      and assist in identifying patients at risk of adverse outcomes, especially among
      patients with reduced EF.

PMID- 27720440
TI  - Allergic rhinitis and allergy are risk factors for otitis media with effusion: A
      meta-analysis.
AB  - OBJECTIVE/HYPOTHESIS: We systematically reviewed the associations between
      allergic rhinitis or allergy and otitis media with effusion, by reference to
      published data. STUDY DESIGN: A meta-analysis of case-controlled studies. DATA
      SOURCE: Five databases (Pubmed, Highwire, Medline, Wanfang, and China National
      Knowledge Infrastructure) were searched for relevant studies in the English
      language published prior to November 12, 2015. STUDIES CHOSEN: Studies with
      clearly defined experimental and control groups, in which the experimental groups
      had otitis media with effusion together with allergic rhinitis or allergy, were
      selected. METHODS: We performed a meta-analysis on data from the identified cross
      sectional and case-controlled studies using fixed- or random-effects models
      (depending on heterogeneity). We used Reviewer Manager 5.3 software to this end.
      RESULTS: Seven studies met the inclusion criteria. The prevalence of allergic
      rhinitis in patients with otitis media with effusion and the control groups
      differed significantly in three studies (P<0.00001), as did the prevalence of
      allergy (in six studies; P=0.003). CONCLUSION: Allergic rhinitis and allergy
      appear to be risk factors for otitis media with effusion.

PMID- 27720441
TI  - Aetiology, imaging features, and evolution of spontaneous perirenal haemorrhage.
AB  - AIM: To evaluate the aetiology, imaging features, and the evolution of
      spontaneous perirenal haemorrhage detected by imaging. MATERIALS AND METHODS: In
      this retrospective study, the hospital database was searched for all cases of
      spontaneous perinephric haemorrhage detected by imaging between January 2000 and
      December 2012. Imaging examinations were reviewed and the following parameters
      were recorded: the location, extension, and total volume of the haematoma,
      presence of active extravasation, the haematocrit effect, and highest density.
      The resolution time was calculated using follow-up imaging. The final aetiology
      for all cases was assessed via clinical, radiological, and histopathological
      data. Differences in imaging features of haemorrhage according to aetiology group
      were analysed with independent samples test and Fisher's exact test. RESULTS:
      Eighty-one haematomas were identified in 78 patients during this 13-year period.
      Causes of perirenal haemorrhage included coagulation disorders (22/81, 27.1%),
      ruptured renal cyst (11/81, 13.6%), rupture of abdominal aortic aneurysm (9/81,
      11.1%), renal cell carcinoma (9/81, 11.1%), adrenal masses (9/81, 11.1%),
      polycystic kidney disease (7/81, 8.6%), angiomyolipoma (6/81, 7.4%), renal
      vascular diseases (2/81, 2.4%), and recurrent pyelonephritis (1/81, 1.2%).
      Haematomas associated with coagulation abnormalities and vascular diseases
      presented with larger volumes and were more likely to extent to the pararenal
      space more so than other groups; ruptured renal cyst and renal cell carcinomas
      tended to be more associated with subcapsular haematomas. The haematocrit effect
      and haemorrhage involving renal parenchyma were more often observed in the group
      with coagulation abnormalities. CONCLUSION: Imaging features, such as location
      and extension, could help radiologists identify possible aetiologies of
      spontaneous perirenal haemorrhage.

PMID- 27720442
TI  - The Global Tobacco Epidemic Requires Further Canadian Action at Home.

PMID- 27720443
TI  - Development of a convenient and supersensitive high-throughput screening system
      for genetically encoded fluorescent probes of small molecules using a confocal
      microscope.
AB  - Monitoring the dynamic patterns of intracellular signaling molecules, such as
      inositol 1,4,5-trisphosphate (IP3) and Ca2+, that control many diverse cellular
      processes, provides us significant information to understand the regulatory
      mechanism of cellular functions. For searching more sensitive and higher dynamic
      range probes for signaling molecules, convenient and supersensitive high
      throughput screening systems are required. Here we show the optimal "in
      Escherichia coli (E. coli) colony" screening method based on the twin-arginine
      translocase (Tat) pathway and introduce a novel application of a confocal
      microscope as a supersensitive detection system to measure changes in the
      fluorescence intensity of fluorescent probes in E. coli grown on an agar plate.
      To verify the performance of the novel detection system, we compared the changes
      detected in the fluorescent intensity of genetically encoded Ca2+ indicator after
      Ca2+ exposure to two kinds of conventional fluorescence detection systems
      (luminescent image analyzer and fluorescence stereomicroscope). The rate of
      fluorescence change between Ca2+ binding and unbinding detected by novel
      supersensitive detection system was almost double than those measured by
      conventional detection systems. We also confirmed that the Tat pathway-based
      screening method is applicable to the development of genetically encoded probes
      for IP3. Our convenient and supersensitive screening system improves the speed of
      developing florescent probes for small molecules.

PMID- 27720444
TI  - Calcium/calmodulin-dependent serine protein kinase CASK modulates the L-type
      calcium current.
AB  - AIM: The L-type voltage-gated calcium channel Cav1.2 mediates the calcium influx
      into cells upon membrane depolarization. The list of cardiopathies associated to
      Cav1.2 dysfunctions highlights the importance of this channel in cardiac
      physiology. Calcium/calmodulin-dependent serine protein kinase (CASK), expressed
      in cardiac cells, has been identified as a regulator of Cav2.2 channels in
      neurons, but no experiments have been performed to investigate its role in Cav1.2
      regulation. METHODS AND RESULTS: Full length or the distal C-terminal truncated
      of the pore-forming Cav1.2 channel (Cav1.2alpha1c), both present in cardiac
      cells, were expressed in TsA-201 cells. In addition, a shRNA silencer, or
      scramble as negative control, of CASK was co-transfected in order to silence CASK
      endogenously expressed. Three days post-transfection, the barium current was
      increased only for the truncated form without alteration of the steady state
      activation and inactivation biophysical properties. The calcium current, however,
      was increased after CASK silencing with both types of Cav1.2alpha1c subunits
      suggesting that, in absence of calcium, the distal C-terminal counteracts the
      CASK effect. Biochemistry experiments did not reveals neither an alteration of
      Cav1.2 channel protein expression after CASK silencing nor an interaction between
      Cav1.2alpha1c subunits and CASK. Nevertheless, after CASK silencing, single
      calcium channel recordings have shown an increase of the voltage-gated calcium
      channel Cav1.2 open probability explaining the increase of the whole-cell
      current. CONCLUSION: This study suggests CASK as a novel regulator of Cav1.2 via
      a modulation of the voltage-gated calcium channel Cav1.2 open probability.

PMID- 27720445
TI  - Outcomes with volume-based dose specification in CT-planned high-dose-rate
      brachytherapy for stage I-II cervical carcinoma: A 10-year institutional
      experience.
AB  - OBJECTIVE: To determine prognostic factors for progression-free survival (PFS)
      and overall survival (OS) for stage I-II cervical-cancer patients treated using
      computed-tomography (CT)-planned high-dose-rate (HDR) intracavitary brachytherapy
      (BT). METHODS: A total of 150 patients were treated for Stage I-II cervical
      cancer using CT-planned BT between 4/2004 and 10/2014. Of these, 128 were
      eligible for inclusion. Kaplan-Meier local control (LC), pelvic control (PC),
      overall survival (OS), and PFS estimates were calculated. RESULTS: After a median
      follow-up of 30months, the 2-year LC rate was 96%, PFS was 88%, and OS was 88%.
      Overall, 18 patients (14%) experienced any recurrence (AR), 8 had distant
      recurrence only and 10 had a combination of local, pelvic, regional, and distant
      recurrence. No patients had LR only. A prognostic factor for AR was tumor size
      >4cm (p=0.01). Patients with tumors >4cm were 3.3 times more likely to have AR
      than those with tumors <=4cm (hazard ratio [HR]=3.3; 95% confidence interval [CI]
      1.28-9.47). Point A was 85% of prescription for tumors < 4 cm and decreased
      approximately 3% over 5 fractions compared to 90% of prescription for tumors > 4
      cm that decreased approximately 4% over 5 fractions. Two patients (2%)
      experienced grade>=2 late toxicity. There were no acute or late grade>=3
      toxicities. CONCLUSION: CT-planned BT resulted in excellent local control and
      survival. Large tumor size was associated with an increased risk of recurrence
      outside the radiation field and worse PFS and OS. A volume-optimized plan treated
      a smaller area than a point A standard plan for patients with Stage I-II cervical
      cancer that have received chemoradiation. Given the outstanding LC achieved with
      modern therapy including chemoradiation, HDR, and image-based BT, further efforts
      to combat spread outside the radiation field with novel therapies are warranted.

PMID- 27720446
TI  - Use of clinical prediction rules and D-dimer tests in the diagnostic management
      of pregnant patients with suspected acute pulmonary embolism.
AB  - Because pregnant women have an increased risk of venous thromboembolism (VTE) and
      at the same time normal pregnancy is associated with symptoms, mimicking those
      present in the setting of acute pulmonary embolism (PE), the latter diagnosis is
      frequently suspected in this patient category. Since imaging tests expose both
      mother and foetus to ionizing radiation, the ability to rule out PE based on non
      radiological diagnostic tests is of paramount importance. However, clinical
      decision rules have only been scarcely evaluated in the pregnant population with
      suspected PE, while D-dimer levels lose diagnostic accuracy due to a
      physiological increase during normal pregnancy. Consequently, clinical guidelines
      provide contradicting and weak recommendations on this subject and the optimal
      diagnostic strategy remains highly debated. With this systematic review, we aimed
      to summarize current evidence on the safety and efficacy of clinical decision
      rules and biomarkers used in the diagnostic management of suspected acute PE in
      pregnant patients.

PMID- 27720447
TI  - Changes in childhood immunization decisions in the United States: Results from
      2012 & 2014 National Parental Surveys.
AB  - OBJECTIVE: Understanding the current status of parents' vaccine decision making
      is crucial to inform public policy. We sought to assess changes in vaccine
      decisions among parents of young children. METHODS: We conducted a web-based
      national poll of parents of children <7years in 2012 and 2014. Participants
      reported vaccine decisions for their youngest child. We calculated survey
      weighted population estimates of overall immunizations decisions, and
      delay/refusal rates for specific vaccines. RESULTS: In 2012, 89.2% (95% CI, 87.3
      90.8%) reported accepting or planning to accept all recommended non-influenza
      childhood vaccines, 5.5% (4.5-6.6%) reported intentionally delaying one or more,
      and 5.4% (4.1-6.9%) reported refusing one or more vaccines. In 2014, the
      acceptance, delay, and refusal rates were 90.8% (89.3-92.1%), 5.6% (4.6-6.9%),
      and 3.6% (2.8-4.5%), respectively. Between 2012 and 2014, intentional vaccine
      refusal decreased slightly among parents of older children (2-6years) but not
      younger children (0-1years). The proportion of parents working to catch up on all
      vaccines increased while those refusing some but not all vaccines decreased. The
      South experienced a significant increase in estimated acceptance (90.1-94.1%) and
      a significant decrease in intentional ongoing refusal (5.0-2.1%). Vaccine delay
      increased in the Northeast (3.2-8.8%). CONCLUSIONS: Nationally, acceptance and
      ongoing intentional delay of recommended non-influenza childhood vaccines were
      stable. These findings suggest that more effort is warranted to counter
      persistent vaccine hesitancy, particularly at the local level. Longitudinal
      monitoring of immunization attitudes is also warranted to evaluate temporal
      shifts over time and geographically.

PMID- 27720448
TI  - Risk factors associated with hospitalisation for influenza-associated severe
      acute respiratory illness in South Africa: A case-population study.
AB  - BACKGROUND: Influenza is a common cause of severe respiratory illness, but risk
      factors for hospitalisation in low income settings with a high HIV prevalence are
      not well described. We aimed to assess risk factors associated with influenza
      associated severe acute respiratory illness (SARI) hospitalisation in South
      Africa. METHODS: We conducted a case-population study using data on risk
      conditions in patients hospitalised with SARI and the national prevalence of
      these conditions. Data on hospitalised cases were from the national SARI
      surveillance program while data on the referent population were from the latest
      national census or health and demographic surveillance surveys. FINDINGS: From
      2009 to 2012, we identified 3646 (7.9%) of 46,031 enrolled cases of SARI that
      were associated with influenza infection. Risk factors associated with
      hospitalisation included previous history of smoking [case-population ratio (CPR)
      3.82, 95% confidence interval (CI) 3.5-4.16], HIV infection (CPR 3.61, 95% CI 3.5
      3.71), asthma (CPR 2.45, 95% CI 2.19-2.73), previous history of hospital
      admission in the past 12months (CPR 2.07, 95% CI 1.92-2.23), and tuberculosis
      (CPR 1.85, 95% CI 1.68-2.02). When stratified by age, there is increased risk of
      hospitalisation in those ?5yearsof age (CPR 3.07, 95% CI 2.93-3.21) and among
      those 35yearsof age and above (CPR 1.23, 95% CI 1.28-1.18). Male sex (CPR 0.85,
      95% CI 0.82-0.88) and completion of pneumococcal conjugate vaccination schedule
      in children <5yearsof age (CPR 0.74, 95% CI 0.71-0.77) were associated with
      decreased risk of hospitalisation. CONCLUSION: These results identify groups at
      high-risk for severe influenza who should be considered potential targets for
      influenza vaccination in South Africa and similar settings.

PMID- 27720449
TI  - Ligand-Dependent Modulation of G Protein Conformation Alters Drug Efficacy.
AB  - G protein-coupled receptor (GPCR) signaling, mediated by hetero-trimeric G
      proteins, can be differentially controlled by agonists. At a molecular level,
      this is thought to occur principally via stabilization of distinct receptor
      conformations by individual ligands. These distinct conformations control
      subsequent recruitment of transducer and effector proteins. Here, we report that
      ligand efficacy at the calcitonin GPCR (CTR) is also correlated with ligand
      dependent alterations to G protein conformation. We observe ligand-dependent
      differences in the sensitivity of the G protein ternary complex to disruption by
      GTP, due to conformational differences in the receptor-bound G protein hetero
      trimer. This results in divergent agonist-dependent receptor-residency times for
      the hetero-trimeric G protein and different accumulation rates for downstream
      second messengers. This study demonstrates that factors influencing efficacy
      extend beyond receptor conformation(s) and expands understanding of the molecular
      basis for how G proteins control/influence efficacy. This has important
      implications for the mechanisms that underlie ligand-mediated biased agonism.
      VIDEO ABSTRACT.

PMID- 27720450
TI  - Competitive Disinhibition Mediates Behavioral Choice and Sequences in Drosophila.
AB  - Even a simple sensory stimulus can elicit distinct innate behaviors and
      sequences. During sensorimotor decisions, competitive interactions among neurons
      that promote distinct behaviors must ensure the selection and maintenance of one
      behavior, while suppressing others. The circuit implementation of these
      competitive interactions is still an open question. By combining comprehensive
      electron microscopy reconstruction of inhibitory interneuron networks, modeling,
      electrophysiology, and behavioral studies, we determined the circuit mechanisms
      that contribute to the Drosophila larval sensorimotor decision to startle,
      explore, or perform a sequence of the two in response to a mechanosensory
      stimulus. Together, these studies reveal that, early in sensory processing, (1)
      reciprocally connected feedforward inhibitory interneurons implement behavioral
      choice, (2) local feedback disinhibition provides positive feedback that
      consolidates and maintains the chosen behavior, and (3) lateral disinhibition
      promotes sequence transitions. The combination of these interconnected circuit
      motifs can implement both behavior selection and the serial organization of
      behaviors into a sequence.

PMID- 27720452
TI  - Kinetic Analysis of Protein Stability Reveals Age-Dependent Degradation.
AB  - Do young and old protein molecules have the same probability to be degraded? We
      addressed this question using metabolic pulse-chase labeling and quantitative
      mass spectrometry to obtain degradation profiles for thousands of proteins. We
      find that >10% of proteins are degraded non-exponentially. Specifically, proteins
      are less stable in the first few hours of their life and stabilize with age.
      Degradation profiles are conserved and similar in two cell types. Many non
      exponentially degraded (NED) proteins are subunits of complexes that are produced
      in super-stoichiometric amounts relative to their exponentially degraded (ED)
      counterparts. Within complexes, NED proteins have larger interaction interfaces
      and assemble earlier than ED subunits. Amplifying genes encoding NED proteins
      increases their initial degradation. Consistently, decay profiles can predict
      protein level attenuation in aneuploid cells. Together, our data show that non
      exponential degradation is common, conserved, and has important consequences for
      complex formation and regulation of protein abundance.

PMID- 27720453
TI  - [New patterns of substance use and abuse among French adolescents, a knowledge
      synthesis].
AB  - AIM: There have been significant changes in adolescent consumption habits over
      the past fifteen years. New molecules have been synthesized, new devices created
      and a number of products have increased in popularity; and as a result clinicians
      sometimes lack information. We chose to focus on this population because of its
      vulnerability, as adolescents show low sensitivity to long-term outcomes of their
      actions and may be easily influenced by peers as regards experimentation of new
      drugs. The most consumed products by adolescents in France are tobacco, alcohol
      and cannabis with the physiological effects and consumption patterns of these
      drugs well documented. The purpose of this review is to identify and describe
      other products that are frequently used by adolescents to get high, to increase
      performance, for purposes of self-medication or because of peer pressure. We
      summarized the current scientific evidence regarding drug availability, physical
      and chemical properties, pharmacodynamics and adverse effects. METHOD: A
      literature review was conducted from 2000 to 2015 based on Pudmed, Google Scholar
      and governmental websites, using the following keyword alone or in combination:
      "adolescent", "new", "misuse", "abuse", "toxicity", "pharmacology" "cocaine",
      "MDMA", "inhalant", "poppers", "magic mushroom", "psilocybin", "designer drug",
      "legal high", "smart drug", "cathinone", "mephedrone", "cannabinoid",
      "prescription drug", "codeine", "opioid", "methylphenidate", "cough syrup",
      "purple drank". RESULTS: New products, including synthetic cannabis, cathinone or
      purple drank seem to be the most dangerous. They are easily accessible and may
      lead to short-term severe or lethal complications. Other substances do not pose a
      major short-term health risk by themselves. However, their consumption may be an
      indication of other unhealthy risk behaviors, such as prescription drug use,
      which may be related to psychiatric comorbidity. Unfortunately, we do not have
      enough data to determine the long-term consequences of the use of these
      substances. Moreover, these products have a strong addictive potential and may be
      a risk factor for other addictions. For this reason, increased supervision is
      justified, both for surveillance and reduction of harm. CONCLUSION: Taking care
      of an adolescent with substance abuse can be difficult. Updated information
      regarding these new substances and the particular danger they pose to adolescent
      health is needed. Informed clinicians can provide up to date and accurate
      information to the patient and family, assess potential risk factors and
      comorbidities, and provide appropriate support. Furthermore, because of the high
      prevalence of substance abuse in the adolescent population, systematic screening
      of adolescent consumption habit is useful to avoid or anticipate complications.
      Often, problematic substance consumption behaviors are signs of more complicated
      psychological or psychiatric issues. Substance abuse behaviors will often
      disappear over time but they can also become a major problem as the adolescent
      moves into adulthood. If problems persist, consultation with an addiction
      specialist may be warranted.

PMID- 27720451
TI  - Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic
      Impact for Metabolic Disease.
AB  - Glucagon and thyroid hormone (T3) exhibit therapeutic potential for metabolic
      disease but also exhibit undesired effects. We achieved synergistic effects of
      these two hormones and mitigation of their adverse effects by engineering
      chemical conjugates enabling delivery of both activities within one precisely
      targeted molecule. Coordinated glucagon and T3 actions synergize to correct
      hyperlipidemia, steatohepatitis, atherosclerosis, glucose intolerance, and
      obesity in metabolically compromised mice. We demonstrate that each hormonal
      constituent mutually enriches cellular processes in hepatocytes and adipocytes
      via enhanced hepatic cholesterol metabolism and white fat browning. Synchronized
      signaling driven by glucagon and T3 reciprocally minimizes the inherent harmful
      effects of each hormone. Liver-directed T3 action offsets the diabetogenic
      liability of glucagon, and glucagon-mediated delivery spares the cardiovascular
      system from adverse T3 action. Our findings support the therapeutic utility of
      integrating these hormones into a single molecular entity that offers unique
      potential for treatment of obesity, type 2 diabetes, and cardiovascular disease.

PMID- 27720455
TI  - Myocardial Fibrosis in Athletes.
AB  - Myocardial fibrosis (MF) is a common phenomenon in the late stages of diverse
      cardiac diseases and is a predictive factor for sudden cardiac death. Myocardial
      fibrosis detected by magnetic resonance imaging has also been reported in
      athletes. Regular exercise improves cardiovascular health, but there may be a
      limit of benefit in the exercise dose-response relationship. Intense exercise
      training could induce pathologic cardiac remodeling, ultimately leading to MF,
      but the clinical implications of MF in athletes are unknown. For this
      comprehensive review, we performed a systematic search of the PubMed and MEDLINE
      databases up to June 2016. Key Medical Subject Headings terms and keywords
      pertaining to MF and exercise (training) were included. Articles were included if
      they represented primary MF data in athletes. We identified 65 athletes with MF
      from 19 case studies/series and 14 athletic population studies. Myocardial
      fibrosis in athletes was predominantly identified in the intraventricular septum
      and where the right ventricle joins the septum. Although the underlying
      mechanisms are unknown, we summarize the evidence for genetic predisposition,
      silent myocarditis, pulmonary artery pressure overload, and prolonged exercise
      induced repetitive micro-injury as contributors to the development of MF in
      athletes. We also discuss the clinical implications and potential treatment
      strategies of MF in athletes.

PMID- 27720454
TI  - Physical Activity and Cognitive Function in Middle-Aged and Older Adults: An
      Analysis of 104,909 People From 20 Countries.
AB  - OBJECTIVE: To examine the associations of physical activity (PA) frequency (both
      moderate and vigorous intensity) and PA levels with cognitive function. PATIENTS
      AND METHODS: Data of individuals 50 years or older, from 20 European countries
      (along with Israel), were collected from 2004 to November 2013 in the biannual
      Survey of Health, Ageing and Retirement in Europe. A total of 104,909
      participants were assessed for cognitive function at least once (mean follow-up
      length, 29.5+/-35.7 months). Baseline moderate- and vigorous-intensity PA were
      reported by participants as more than once a week, once a week, one to three
      times a month, or hardly ever or never. With regard to PA frequency, participants
      were categorized as inactive, low active, intermediate active, or high active.
      The main outcome measure is a cognitive composite score created by summing the z
      scores of 4-item temporal orientation, 10-word list for delayed recall, and
      verbal fluency. RESULTS: Adjusted, 2-level mixed-effect regressions found that
      compared with doing no PA, doing PA more than once a week, once a week, or one to
      three times a month was positively associated with the composite score (beta
      coefficients varied from 0.52 to 0.75 for moderate-intensity PA and from 0.26 to
      0.33 for vigorous-intensity PA). Similarly, compared with the inactive category,
      high-active, intermediate-active, and low-active categories had positive
      associations with the composite score (beta varied from 0.77 to 1.10). Positive
      associations were also obtained between PA variables and the raw scores of
      cognitive tests. CONCLUSION: Physical activity has dose-response associations
      with cognitive function, with even low PA frequencies (few times per month) being
      positively associated with cognitive function during aging.

PMID- 27720456
TI  - Impact of Stress Testing for Coronary Artery Disease Screening in Asymptomatic
      Patients With Diabetes Mellitus: A Community-Based Study in Olmsted County,
      Minnesota.
AB  - OBJECTIVE: To evaluate the impact of screening stress testing for coronary artery
      disease in asymptomatic patients with diabetes in a community-based population.
      PATIENTS AND METHODS: This observational study included 3146 patients from
      Olmsted County, Minnesota, with no history of coronary artery disease or cardiac
      symptoms in whom diabetes was newly diagnosed from January 1, 1992, through
      December 31, 2008. With combined all-cause mortality and myocardial infarction as
      the primary outcome, weighted Cox proportional hazards regression was performed
      with screening stress testing within 2 years of diabetes diagnosis as the time
      dependent covariate. For descriptive analysis, participants were classified by
      their clinical experience during the first 2 years postdiagnosis as screened
      (asymptomatic, underwent stress test), unscreened (asymptomatic, no stress test),
      or symptomatic (experienced symptoms or event). RESULTS: Among the screened and
      unscreened participants, 54% (1358 of 2538) were men; the mean (SD) age at
      diabetes diagnosis was 55 years (13.8 years), and 97% (2442 of 2520) had type 2
      diabetes. In event-free survival analysis, 292 patients comprised the screened
      cohort and 2246 patients comprised the unscreened cohort. Death or myocardial
      infarction occurred in 454 patients (32 patients in the screened cohort and 422
      in the unscreened cohort [5-year rate, 1.9% and 5.3%, respectively]) during
      median (interquartile range) follow-up of 9.1 years (5.3-12.5 years). Screening
      stress testing was associated with improved event-free survival (hazard ratio,
      0.61; P=.004), independent of cardiac risk factors. However, while stress test
      results were abnormal in 47 of the 292 screened patients (16%), only 6 (2%)
      underwent coronary revascularization. CONCLUSION: Although screening cardiac
      stress testing in asymptomatic patients with diabetes in this community-based
      population was associated with improvement in long-term event-free survival, this
      result does not appear to occur by coronary revascularization alone.

PMID- 27720457
TI  - Positive Airway Pressure Therapy for Obstructive Sleep Apnea.
AB  - Positive airway pressure (PAP) is considered first-line therapy for moderate to
      severe obstructive sleep apnea and may also be considered for mild obstructive
      sleep apnea, particularly if it is symptomatic or there are concomitant
      cardiovascular disorders. Continuous PAP is most commonly used. Other modes, such
      as bilevel airway pressure, autotitrating positive airway pressure, average
      volume assured pressure support, and adaptive support ventilation, play important
      roles in the management of sleep-related breathing disorders. This article
      outlines the indications, description, and comfort features of each mode. Despite
      the proven efficacy of PAP in treating obstructive sleep apnea syndrome and its
      sequelae, adherence to therapy is low. Close follow-up of patients for evaluation
      of adherence to and effectiveness of treatment is important.

PMID- 27720458
TI  - Upper Airway Stimulation Therapy.
AB  - Traditional upper airway surgery directly modifies skeletal and soft tissue
      structures surrounding the airway to treat obstructive sleep apnea (OSA). Upper
      airway stimulation (UAS) attempts to treat upper airway obstruction and OSA by
      stimulating the hypoglossal nerve. The Inspire II implant has been approved for
      clinical UAS. Basic science data support that UAS prevents obstruction and
      improves airflow. Clinical results demonstrate that UAS improves respiratory
      sleep metrics and improves both objective and subjective self-reported sleep and
      quality-of-life outcomes. In a substantial number of individuals who meet
      inclusion criteria, UAS appears to be a viable, long-term, low-morbidity
      treatment of moderate-to-severe OSA.

PMID- 27720459
TI  - Skeletal Surgery for Obstructive Sleep Apnea.
AB  - Multilevel surgery has been established as the mainstay of treatment for the
      surgical management of obstructive sleep apnea (OSA). Combined with
      uvulopalatopharyngoplasty, tongue-base surgeries, including the genioglossus
      advancement (GA), sliding genioplasty, and hyoid myotomy and suspension, have
      been developed to target hypopharyngeal obstruction. Total airway surgery
      consisting of maxillomandibular advancement (MMA) with/without GA has shown
      significant success. Skeletal procedures for OSA with or without a palatal
      procedure is a proven technique for relieving airway obstruction during sleep. A
      case study demonstrating the utility of virtual surgical planning for MMA surgery
      is presented.

PMID- 27720460
TI  - Palatal Procedures for Obstructive Sleep Apnea.
AB  - Uvulopalatopharyngoplasty was the first surgical procedure described, other than
      tracheostomy, for the treatment of obstructive sleep apnea (OSA) in 1981. It was
      recognized then that there were responders who were cured of OSA with the
      procedure and others that were not. It took many years for a staging system to be
      described that categorized patients based on Mallampati score, tonsil size, and
      body mass index to better predict success rates. It was recognized that
      individuals with retro-palatal obstruction as the cause of the airway obstruction
      responded well but that the morbidity associated with the inpatient procedure was
      often problematic.

PMID- 27720461
TI  - Oral Appliances in Obstructive Sleep Apnea.
AB  - Oral appliance therapy (OAT) has become an increasingly popular nonsurgical
      option for the treatment of obstructive sleep disorders. Recent research supports
      its efficacy and high levels of compliance for patients with obstructive sleep
      disorders. Common side effects of OAT include temporomandibular joint-related
      symptoms, bite changes, and tooth movement. These side effects can be minimized
      by the use of exercises. The American Academy of Dental Sleep Medicine and the
      American Academy of Sleep Medicine have released joint clinical practice
      guidelines for the treatment of obstructive sleep apnea and snoring with OAT.

PMID- 27720462
TI  - An Introduction to Obstructive Sleep Apnea.
AB  - Obstructive sleep apnea (OSA) is a prevalent disease entity that has become
      commonplace over the past few decades. Its surge in diagnosis can be linked to a
      better understanding of the process with a concurrent increase in prevalence. The
      social, economic, and personal impacts are significant; there continues to be a
      need to improve our treatment modalities for OSA.

PMID- 27720463
TI  - Nasal Surgery for Obstructive Sleep Apnea Syndrome.
AB  - Obstructive sleep apnea is a common condition, primarily caused by narrowing of
      the nasal and pharyngeal airway. Treatment with continuous positive airway
      pressure (CPAP) is considered the first line of therapy, but long-term compliance
      is only about 40%, often because of nasal obstruction. Any nasal obstruction can
      worsen CPAP compliance. Treatment of the nasal obstruction with topical nasal
      steroid sprays or nasal dilators has been shown to improve sleep disordered
      breathing. Surgical treatment of nasal obstruction, has been shown to improve
      sleep disordered breathing, as well as CPAP requirement and compliance with CPAP.

PMID- 27720464
TI  - The skin aging exposome.
AB  - The term "exposome" describes the totality of exposures to which an individual is
      subjected from conception to death. It includes both external and internal
      factors as well as the human body's response to these factors. Current exposome
      research aims to understand the effects all factors have on specific organs, yet
      today, the exposome of human skin has not received major attention and a
      corresponding definition is lacking. This review was compiled with the
      collaboration of European scientists, specialized in either environmental
      medicine or skin biology. A comprehensive review of the existing literature was
      performed using PubMed. The search was restricted to exposome factors and skin
      aging. Key review papers and all relevant, epidemiological, in vitro, ex vivo and
      clinical studies were analyzed to determine the key elements of the exposome
      influencing skin aging. Here we propose a definition of the skin aging exposome.
      It is based on a summary of the existing scientific evidence for the role of
      exposome factors in skin aging. We also identify future research needs which
      concern knowledge about the interaction of distinct exposomal factors with each
      other and the resulting net effects on skin aging and suggest some protective
      measures.

PMID- 27720466
TI  - Differential diagnosis of herpetiform vesicles by a non-invasive, molecular
      method using crusts or blister roofs: Sensitivity, specificity and likelihood
      ratio.

PMID- 27720465
TI  - Inhibition of aryl hydrocarbon receptor signaling and induction of NRF2-mediated
      antioxidant activity by cinnamaldehyde in human keratinocytes.
AB  - BACKGROUND: Dioxins and other environmental pollutants are toxic and remain in
      biological tissues for a long time leading to various levels of oxidative stress.
      Although the toxicity of these agents has been linked to activation of the aryl
      hydrocarbon receptor (AHR), no effective treatment has been developed. OBJECTIVE:
      To explore novel phytochemicals that inhibit AHR activation in keratinocytes.
      METHODS: Keratinocytes were used in this study because the skin is one of the
      organs most affected by dioxin and other environmental pollutants. HaCaT cells,
      which are a human keratinocyte cell line, and normal human epidermal
      keratinocytes were stimulated with benzo[a]pyrene to induce AHR activation, and
      the effects of traditional Japanese Kampo herbal formulae were analyzed.
      Quantification of mRNA, western blotting, immunofluorescence localization of
      molecules, siRNA silencing, and visualization of oxidative stress were performed.
      RESULTS: Cinnamomum cassia extract and its major constituent cinnamaldehyde
      significantly inhibited the activation of AHR. Cinnamaldehyde also activated the
      NRF2/HO1 pathway and significantly alleviated the production of reactive oxygen
      species in keratinocytes. The inhibition of AHR signaling and the activation of
      antioxidant activity by cinnamaldehyde operated in a mutually independent manner
      as assessed by siRNA methods In addition, AHR signaling was effectively inhibited
      by traditional Kampo formulae containing C. cassia. CONCLUSION: Cinnamaldehyde
      has two independent biological activities; namely, an inhibitory action on AHR
      activation and an antioxidant effect mediated by NRF2/HO1 signaling. Through
      these dual functions, cinnamaldehyde may be beneficial for the treatment of
      disorders related to oxidative stress such as dioxin intoxication, acne, and
      vitiligo.

PMID- 27720467
TI  - Dynamic safety assessment of natural gas stations using Bayesian network.
AB  - Pipelines are one of the most popular and effective ways of transporting
      hazardous materials, especially natural gas. However, the rapid development of
      gas pipelines and stations in urban areas has introduced a serious threat to
      public safety and assets. Although different methods have been developed for risk
      analysis of gas transportation systems, a comprehensive methodology for risk
      analysis is still lacking, especially in natural gas stations. The present work
      is aimed at developing a dynamic and comprehensive quantitative risk analysis
      (DCQRA) approach for accident scenario and risk modeling of natural gas stations.
      In this approach, a FMEA is used for hazard analysis while a Bow-tie diagram and
      Bayesian network are employed to model the worst-case accident scenario and to
      assess the risks. The results have indicated that the failure of the regulator
      system was the worst-case accident scenario with the human error as the most
      contributing factor. Thus, in risk management plan of natural gas stations,
      priority should be given to the most probable root events and main contribution
      factors, which have identified in the present study, in order to reduce the
      occurrence probability of the accident scenarios and thus alleviate the risks.

PMID- 27720468
TI  - Superb adsorption capacity of hierarchical calcined Ni/Mg/Al layered double
      hydroxides for Congo red and Cr(VI) ions.
AB  - The preparation of hierarchical porous materials as catalysts and sorbents has
      attracted much attention in the field of environmental pollution control. Herein,
      Ni/Mg/Al layered double hydroxides (NMA-LDHs) hierarchical flower-like hollow
      microspheres were synthesized by a hydrothermal method. After the NMA-LDHs was
      calcined at 600 degrees C, NMA-LDHs transformed into Ni/Mg/Al layered double
      oxides (NMA-LDOs), which maintained the hierarchical flower-like hollow
      structure. The crystal phase, morphology, and microstructure of the as-prepared
      samples were characterized by X-ray diffraction, scanning electron microscopy,
      transmission electron microscopy, energy-dispersive X-ray spectroscopy elemental
      mapping, Fourier transform infrared spectroscopy, and nitrogen adsorption
      desorption methods. Both the calcined and non-calcined NMA-LDHs were examined for
      their performance to remove Congo red (CR) and hexavalent chromium (Cr(VI)) ions
      in aqueous solution. The maximum monolayer adsorption capacities of CR and Cr(VI)
      ions over the NMA-LDOs sample were 1250 and 103.4mg/g at 30 degrees C,
      respectively. Thermodynamic studies indicated that the adsorption process was
      endothermic in nature. In addition, the addition of coexisting anions negatively
      influenced the adsorption capacity of Cr(VI) ions, in the following order: CO32
      >SO42->H2PO4->Cl-. This work will provide new insight into the design and
      fabrication of advanced adsorption materials for water pollutant removal.

PMID- 27720469
TI  - Complete removal of arsenic and zinc from a heavily contaminated acid mine
      drainage via an indigenous SRB consortium.
AB  - Acid mine drainages (AMD) are major sources of pollution to the environment.
      Passive bio-remediation technologies involving sulfate-reducing bacteria (SRB)
      are promising for treating arsenic contaminated waters. However, mechanisms of
      biogenic As-sulfide formation need to be better understood to decontaminate AMDs
      in acidic conditions. Here, we show that a high-As AMD effluent can be
      decontaminated by an indigenous SRB consortium. AMD water from the Carnoules mine
      (Gard, France) was incubated with the consortium under anoxic conditions and As,
      Zn and Fe concentrations, pH and microbial activity were monitored during 94days.
      Precipitated solids were analyzed using electron microscopy (SEM/TEM-EDXS), and
      Extended X-Ray Absorption Fine Structure (EXAFS) spectroscopy at the As K-edge.
      Total removal of arsenic and zinc from solution (1.06 and 0.23mmol/L,
      respectively) was observed in two of the triplicates. While Zn precipitated as
      ZnS nanoparticles, As precipitated as amorphous orpiment (am-AsIII2S3) (33-73%),
      and realgar (AsIIS) (0-34%), the latter phase exhibiting a particular nanowire
      morphology. A minor fraction of As is also found as thiol-bound AsIII (14-23%).
      We propose that the formation of the AsIIS nanowires results from AsIII2S3
      reduction by biogenic H2S, enhancing the efficiency of As removal. The present
      description of As immobilization may help to set the basis for bioremediation
      strategies using SRB.

PMID- 27720470
TI  - Metagenomic insight into the bioaugmentation mechanism of Phanerochaete
      chrysosporium in an activated sludge system treating coking wastewater.
AB  - Phanerochaete chrysosporium was seeded to a sequencing batch reactor treating
      phenol wastewater. Compared to the contrast reactor (R1), the bioaugmented
      reactor (R2) exhibits better performance in sludge settling ability, as well as
      biomass and phenol removal, even though the added fungus is not persistently
      surviving in the reactor. Bioaugmentation improved bacterial population, growing
      up to 10,000 times higher than that of eukaryotes. Metagenomic sequencing results
      show the bioaugmentation finally increases bacterial and eukaryotic richness, but
      reduces their community diversity. In contrast to R1, bacterial distribution in
      R2 is more concentrated in Proteobacteria. The relative abundances of filamentous
      fungi, yeast and microalgae in R2 are all higher than those in R1 at different
      treatment phases, and two reactors are finally dominated by different protozoan
      and metazoan. In conclusion, P. chrysosporium improves reactor performances by
      influencing microbial community structure, and this phenomenon might be
      attributed to the ecological competition in sludge and toxicity reduction of
      phenol wastewater. The novelty of this study emphasizes why a species which is
      not persistently active in bioreactor still plays a crucial role in enhancing
      reactor performance. Results obtained here impact the conventional criteria for
      selection of bioaugmentation microbes used in activated sludge systems.

PMID- 27720471
TI  - Physiological and behavioural impacts of Pacific ciguatoxin-1 (P-CTX-1) on marine
      medaka (Oryzias melastigma).
AB  - Ciguatoxins (CTXs) are natural biotoxins produced by benthic dinoflagellates of
      the genus Gambierdiscus, which are bioaccumulated and biotransformed along food
      chains in coral ecosystems. They are neurotoxins that activate voltage-gated
      sodium channels and disrupt ion conductance in the excitable tissues. Pacific
      ciguatoxin-1 (P-CTX-1) is the most prevalent and potent CTX congener present in
      fishes from the Pacific Ocean. In this study, P-CTX-1 was administrated to larval
      marine medaka (2h post-hatch) via microinjection. Exposure to P-CTX-1 at sub-ppb
      levels led to adverse behavioural changes, altered physiological performances and
      reduced survivability of the larval marine medaka as early as 24h after exposure.
      P-CTX-1 decreased the rate of heartbeat and locomotion of the exposed larvae,
      probably owing to a series of physiological processes and morphological changes
      such as pericardial oedema, failure of swim bladder inflation and spinal
      curvature. The exposed larval marine medaka also demonstrated reduced, delayed
      and paralyzed responses to external stimulations. This may render them more
      susceptible to predation. P-CTX-1 could be effectively distributed from the yolk
      sac to all parts of the fish body, including head and trunk, 24h after exposure.
      Repeated low-dose P-CTX-1 exposure resulted in larval mortality comparable to
      that of a single high-dose exposure.

PMID- 27720472
TI  - Viability of a nanoremediation  process in single or multi-metal(loid)
      contaminated soils.
AB  - The effectiveness of single- and multi-metal(loid) immobilization of As, Cd, Cr,
      Pb and Zn using different doses of nanoscale zero-valent iron (nZVI) was
      evaluated and compared in two different soils, a calcareous and an acidic one.
      The effectiveness of nZVI to immobilize metal(loid)s in soil strongly depended on
      the metal characteristics, soil properties, dose of nZVI and presence of other
      metal(loid)s. In the case of single contamination, this nanoremediation strategy
      was effective for all of the metal(loid)s studied except for Cd. When comparing
      the two soils, anionic metal(loid)s (As and Cr) were more easily retained in
      acidic soil, whereas cationic metal(loid)s (Cd, Pb and Zn), were immobilized more
      in calcareous soil. In multi-metal(loid) contaminated soils, the presence of
      several metal(loid)s affected their immobilization, which was probably due to the
      competitive phenomenon between metal(loid) ions, which can reduce their sorption
      or produce synergistic effects. At 10% of nZVI, As, Cr and Pb availability
      decreased more than 82%, for Zn it ranged between 31 and 75% and for Cd between
      13 and 42%. Thus, the application of nZVI can be a useful strategy to immobilize
      As, Cr, Pb and Zn in calcareous or acidic soils in both single- or multi
      metal(loid) contamination conditions.

PMID- 27720473
TI  - Microaerobic degradation of 2-Mercaptobenzothiazole present in industrial
      wastewater.
AB  - Microaerobic degradation of 2-Mercaptobenzothiazole (2-MBT) was investigated
      using an isolated bacterial strain CSMB1. It was identified as Alcaligenes sp.
      MH146 by genomic analysis. The isolate degraded 50mg/L concentration of 2-MBT
      which was measured in terms of Total organic carbon (TOC) (700mg/L). A maximum
      degradation of 86% with a residual TOC concentration of 101mg/L was obtained
      after 72h, with the biomass growth of 290mg/L. The presence of specific activity
      of catechol 2, 3 oxygenase was observed in all the tested derivatives of
      benzothiazoles and the benzene ring opening was observed through meta cleavage.
      By analyzing the 72h incubated culture supernatant, 2-MBT, and all its
      biotransformed products were degraded into polar compounds. With the analytical
      results obtained, a possible microaerobic degradative pathway was proposed and
      illustrated for 2-MBT. It is concluded that microaerophilic isolate CSMB1 was
      able to degrade 2-MBT and its intermediates by utilizing them as sole carbon and
      energy.

PMID- 27720474
TI  - Modeling and Elucidation of the Kinetics of Multiple Consecutive Photoreactions
      AB4(4Phi) With Phi-order Kinetics. Application to the Photodegradation of
      Riboflavin.
AB  - New semi-empirical rate-law system of equations is proposed for the first time
      for consecutive photoreactions that involve up to 4 photoreaction steps,
      AB4(4Phi). The equation system was developed, tested, and validated against
      synthetic kinetic traces generated by fifth-order Runge-Kutta calculations. The
      model accurately fitted the kinetic traces of Riboflavin photodegradation in
      ethanol which decomposes via the AB2(2Phi) mechanism involving 2 consecutive
      photoreaction steps. A kinetic elucidation methodology useful for consecutive
      photoreactions was also proposed to determine all the kinetic parameters and
      reaction attributes defining AB2(2Phi) reactions. The quantum yields of
      photodegradation, determined for wavelengths in the visible region 400-480 nm,
      ranged from 0.005 to 0.00756 and 0.0012 to 8 10-5 for the first and second
      photoreaction steps, respectively. They were found to increase with wavelength in
      defined sigmoid functions. For this monochromatic irradiation range, riboflavin
      proved to be a useful actinometer. Finally, a photodegradation scale based on
      pseudo-rate-constant values was also proposed for drugs. This scale (including 4
      groups) is thought to contribute to rationalizing photodegradation testing and
      might prove useful in categorizing drugs' photodegradation reactivity.

PMID- 27720475
TI  - Perioperative detection of alcoholic cardiomyopathy: cases and recommendations.

PMID- 27720476
TI  - Nanominerals and potentially hazardous elements from coal cleaning rejects of
      abandoned mines: Environmental impact and risk assessment.
AB  - Soils around coal mining are important reservoir of hazardous elements (HEs),
      nanominerals, and ultrafine compounds. This research reports and discusses the
      soil concentrations of HEs (As, Cd, Cr, Cu, Ni, Pb, and Zn) in coal residues of
      abandoned mines. To assess differences regarding environmental impact and risk
      assessment between coal abandoned mines from the Santa Catarina state, eighteen
      coal cleaning rejects with different mineralogical and chemical composition, from
      eight abandoned mines were collected. Nanominerals and ultra-fine minerals from
      mining-contaminated areas were analyzed by X-ray diffraction (XRD), field
      emission scanning electron microscopy (FE-SEM), and high-resolution transmission
      electron microscope (HR-TEM), providing new information on the mineralogy and
      nano-mineralogy of these coal residues. The total contents of 57 elements (HEs,
      alkali metals, and rare earth elements) were analyzed by Inductively Coupled
      Plasma Mass Spectrometry (ICP-MS). The calculation of NWACs (Normalized Average
      Weighted Concentration), together with the chemometric analysis by Principal
      component analysis (PCA) confirmed the variability of the samples regarding their
      city and their mine of origin. Moreover, the results confirmed the existence of
      hotspots in mines near urban areas.

PMID- 27720477
TI  - Hybrid controller with observer for the estimation and rejection of disturbances.
AB  - In this paper, a hybrid controller with observer is introduced for the estimation
      and rejection of a disturbance. It is based on the combination of the sliding
      mode technique and the output feedback strategy. It is divided into two designs:
      (1) the observer and (2) the controller with observer. The observer is selected
      to reach two objectives: (a) to assure its stability and (b) for the estimation
      of a disturbance. The controller with observer is selected to reach three
      objectives: (a) to assure its stability, (b) for the rejection of a disturbance,
      and (c) for the decreasing of chattering in the sliding mode behavior. The
      proposed method is applied for the estimation and rejection of the disturbance in
      a plotter and a suspension system.

PMID- 27720478
TI  - Erratum to "Sunitinib in patients with advanced thymic malignancies: cohort from
      the French RYTHMIC network" [Lung Cancer, 97 (July 2016), 99-104].

PMID- 27720479
TI  - Two cases of thermal burns of the larynx in older men.
AB  - Cases of thermal burns of the larynx in infants and in patients with mental
      illness have been reported, but those in older people are rare. We report two
      cases of thermal burns of the larynx in older people caused by ingestion of
      microwave-heated food (meat and potato stew or a bean-jam filled bun). Both
      patients were users of full dentures. Conservative therapy was effective in one
      patient, while tracheotomy was performed in the other patient at the time of the
      initial examination. Hot food is expelled from the mouth as a reflective
      response, preventing thermal burns of the larynx. However, in older individuals,
      sense perception is impaired and reflexes are slowed. Further, the oral mucosa is
      protected if full dentures are placed. Therefore, heat is likely to not be
      perceived and reflexes occur only after the food has reached the larynx, thereby
      causing thermal burns of the larynx. The number of such cases may increase as the
      number of older patients rises in the current aging society. Therefore, raising
      awareness of such cases is important.

PMID- 27720480
TI  - Basaloid squamous cell carcinoma arising in an inverted papilloma in the nasal
      cavity: A case report and review.
AB  - Basaloid squamous cell carcinoma (BSCC) is a histologically distinctive variant
      of squamous cell carcinoma comprising basal cell carcinoma and squamous cell
      carcinoma. BSCC is aggressive and shows a poor prognosis because of frequent
      lymph node invasion and distant metastases. BSCC preferentially occurs in the
      cervix, thymus, and esophagus and is uncommonly found in the head and neck
      region. BSCC in the nasal cavity or paranasal sinus is particularly rare.
      Inverted papilloma is an uncommon, benign tumor with a propensity to be
      associated with malignancy; however, BSCC arising in an inverted papilloma has
      never been reported. Here we report a case of a 56-year-old woman with BSCC
      arising in an inverted papilloma in the nasal cavity. The woman was referred to
      our hospital for epistaxis, nasal congestion, and dysphagia. A tumor was observed
      to completely occupy the left nasal cavity. The biopsy specimen was
      histologically diagnosed as papilloma. Computed tomography demonstrated a tumor
      with heterogeneous contrast effect occupying the left nasal cavity; however,
      extra-nasal tract extension was not observed. We performed endoscopic excision of
      the tumor. Microscopic findings confirmed the diagnosis of BSCC arising from an
      inverted papilloma. No tumor recurrence has been observed for 13 months after
      surgery.

PMID- 27720482
TI  - Laminar Module Cascade from Layer 5 to 6 Implementing Cue-to-Target Conversion
      for Object Memory Retrieval in the Primate Temporal Cortex.
AB  - The cerebral cortex computes through the canonical microcircuit that connects six
      stacked layers; however, how cortical processing streams operate in vivo,
      particularly in the higher association cortex, remains elusive. By developing a
      novel MRI-assisted procedure that reliably localizes recorded single neurons at
      resolution of six individual layers in monkey temporal cortex, we show that
      transformation of representations from a cued object to a to-be-recalled object
      occurs at the infragranular layer in a visual cued-recall task. This cue-to
      target conversion started in layer 5 and was followed by layer 6. Finally, a
      subset of layer 6 neurons exclusively encoding the sought target became phase
      locked to surrounding field potentials at theta frequency, suggesting that this
      coordinated cell assembly implements cortical long-distance outputs of the
      recalled target. Thus, this study proposes a link from local computation spanning
      laminar modules of the temporal cortex to the brain-wide network for memory
      retrieval in primates.

PMID- 27720481
TI  - Poly(GR) in C9ORF72-Related ALS/FTD Compromises Mitochondrial Function and
      Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons.
AB  - GGGGCC repeat expansions in C9ORF72 are the most common genetic cause of both ALS
      and FTD. To uncover underlying pathogenic mechanisms, we found that DNA damage
      was greater, in an age-dependent manner, in motor neurons differentiated from
      iPSCs of multiple C9ORF72 patients than control neurons. Ectopic expression of
      the dipeptide repeat (DPR) protein (GR)80 in iPSC-derived control neurons
      increased DNA damage, suggesting poly(GR) contributes to DNA damage in aged
      C9ORF72 neurons. Oxidative stress was also increased in C9ORF72 neurons in an age
      dependent manner. Pharmacological or genetic reduction of oxidative stress
      partially rescued DNA damage in C9ORF72 neurons and control neurons expressing
      (GR)80 or (GR)80-induced cellular toxicity in flies. Moreover, interactome
      analysis revealed that (GR)80 preferentially bound to mitochondrial ribosomal
      proteins and caused mitochondrial dysfunction. Thus, poly(GR) in C9ORF72 neurons
      compromises mitochondrial function and causes DNA damage in part by increasing
      oxidative stress, revealing another pathogenic mechanism in C9ORF72-related ALS
      and FTD.

PMID- 27720483
TI  - The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the
      Adult CNS.
AB  - Injuries to the adult CNS often result in permanent disabilities because neurons
      lose the ability to regenerate their axon during development. Here, whole
      transcriptome sequencing and bioinformatics analysis followed by gain- and loss
      of-function experiments identified Cacna2d2, the gene encoding the Alpha2delta2
      subunit of voltage-gated calcium channels (VGCCs), as a developmental switch that
      limits axon growth and regeneration. Cacna2d2 gene deletion or silencing promoted
      axon growth in vitro. In vivo, Alpha2delta2 pharmacological blockade through
      Pregabalin (PGB) administration enhanced axon regeneration in adult mice after
      spinal cord injury (SCI). As PGB is already an established treatment for a wide
      range of neurological disorders, our findings suggest that targeting Alpha2delta2
      may be a novel treatment strategy to promote structural plasticity and
      regeneration following CNS trauma.

PMID- 27720484
TI  - A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at
      Presynaptic Terminals.
AB  - Synapses are often far from the soma and independently cope with proteopathic
      stress induced by intense neuronal activity. However, how presynaptic
      compartments turn over proteins is poorly understood. We show that the synapse
      enriched protein EndophilinA, thus far studied for its role in endocytosis,
      induces macroautophagy at presynaptic terminals. We find that EndophilinA
      executes this unexpected function at least partly independent of its role in
      synaptic vesicle endocytosis. EndophilinA-induced macroautophagy is activated
      when the kinase LRRK2 phosphorylates the EndophilinA-BAR domain and is blocked in
      animals where EndophilinA cannot be phosphorylated. EndophilinA-phosphorylation
      promotes the formation of highly curved membranes, and reconstitution experiments
      show these curved membranes serve as docking stations for autophagic factors,
      including Atg3. Functionally, deregulation of the EndophilinA phosphorylation
      state accelerates activity-induced neurodegeneration. Given that EndophilinA is
      connected to at least three Parkinson's disease genes (LRRK2, Parkin and
      Synaptojanin), dysfunction of EndophilinA-dependent synaptic macroautophagy may
      be common in this disorder.

PMID- 27720485
TI  - Reduction of Nuak1 Decreases Tau and Reverses Phenotypes in a Tauopathy Mouse
      Model.
AB  - Many neurodegenerative proteinopathies share a common pathogenic mechanism: the
      abnormal accumulation of disease-related proteins. As growing evidence indicates
      that reducing the steady-state levels of disease-causing proteins mitigates
      neurodegeneration in animal models, we developed a strategy to screen for genes
      that decrease the levels of tau, whose accumulation contributes to the pathology
      of both Alzheimer disease (AD) and progressive supranuclear palsy (PSP).
      Integrating parallel cell-based and Drosophila genetic screens, we discovered
      that tau levels are regulated by Nuak1, an AMPK-related kinase. Nuak1 stabilizes
      tau by phosphorylation specifically at Ser356. Inhibition of Nuak1 in fruit flies
      suppressed neurodegeneration in tau-expressing Drosophila, and Nuak1
      haploinsufficiency rescued the phenotypes of a tauopathy mouse model. These
      results demonstrate that decreasing total tau levels is a valid strategy for
      mitigating tau-related neurodegeneration and reveal Nuak1 to be a novel
      therapeutic entry point for tauopathies.

PMID- 27720486
TI  - A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons.
AB  - Efficient retrograde access to projection neurons for the delivery of sensors and
      effectors constitutes an important and enabling capability for neural circuit
      dissection. Such an approach would also be useful for gene therapy, including the
      treatment of neurodegenerative disorders characterized by pathological spread
      through functionally connected and highly distributed networks. Viral vectors, in
      particular, are powerful gene delivery vehicles for the nervous system, but all
      available tools suffer from inefficient retrograde transport or limited clinical
      potential. To address this need, we applied in vivo directed evolution to
      engineer potent retrograde functionality into the capsid of adeno-associated
      virus (AAV), a vector that has shown promise in neuroscience research and the
      clinic. A newly evolved variant, rAAV2-retro, permits robust retrograde access to
      projection neurons with efficiency comparable to classical synthetic retrograde
      tracers and enables sufficient sensor/effector expression for functional circuit
      interrogation and in vivo genome editing in targeted neuronal populations. VIDEO
      ABSTRACT.

PMID- 27720487
TI  - Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA
      Signaling in the Ventral Tegmental Area.
AB  - Stress is a well-known risk factor for subsequent alcohol abuse, but the neural
      mechanisms underlying interactions between stress and alcohol remain largely
      unknown. Addictive drug reinforcement and stress signaling involve common neural
      circuitry, including the mesolimbic dopamine system. We demonstrate in rodents
      that pre-exposure to stress attenuates alcohol-induced dopamine responses and
      increases alcohol self-administration. The blunted dopamine signaling resulted
      from ethanol-induced excitation of GABA neurons in the ventral tegmental area.
      Excitation of GABA neurons was mediated by GABAA receptor activation and involved
      stress-induced functional downregulation of the K+, Cl- cotransporter, KCC2.
      Blocking stress hormone receptors, enhancing KCC2 function, or preventing
      excitatory GABA signaling by alternative methods all prevented the attenuated
      alcohol-induced dopamine response and prevented the increased alcohol self
      administration. These results demonstrate that stress alters the neural and
      behavioral responses to alcohol through a neuroendocrine signal that shifts
      inhibitory GABA transmission toward excitation.

PMID- 27720489
TI  - Pro: Atrial Fibrillation Prophylaxis Is Recommended in Patients Undergoing Major
      Thoracic Surgery.

PMID- 27720488
TI  - Amygdala and Ventral Striatum Make Distinct Contributions to Reinforcement
      Learning.
AB  - Reinforcement learning (RL) theories posit that dopaminergic signals are
      integrated within the striatum to associate choices with outcomes. Often
      overlooked is that the amygdala also receives dopaminergic input and is involved
      in Pavlovian processes that influence choice behavior. To determine the relative
      contributions of the ventral striatum (VS) and amygdala to appetitive RL, we
      tested rhesus macaques with VS or amygdala lesions on deterministic and
      stochastic versions of a two-arm bandit reversal learning task. When learning was
      characterized with an RL model relative to controls, amygdala lesions caused
      general decreases in learning from positive feedback and choice consistency. By
      comparison, VS lesions only affected learning in the stochastic task. Moreover,
      the VS lesions hastened the monkeys' choice reaction times, which emphasized a
      speed-accuracy trade-off that accounted for errors in deterministic learning.
      These results update standard accounts of RL by emphasizing distinct
      contributions of the amygdala and VS to RL.

PMID- 27720490
TI  - A Retrospective Analysis of the Influence of Ventricular Morphology on the
      Perioperative Outcomes After Fontan Surgery.
AB  - OBJECTIVES: The objectives of this study were to evaluate the effect of
      ventricular morphology on perioperative outcomes during Fontan surgery. DESIGN:
      Retrospective cohort study. SETTING: Single standing, not-for-profit pediatric
      hospital. PARTICIPANTS: A total of 72 patients who underwent Fontan surgery using
      cardiopulmonary bypass without aortic cross-clamp between January 1, 2009 and
      December 31, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The
      patients were divided into 3 categories depending on their single-ventricle
      lesions: (1) LV group (n = 20): left dominant and hypoplastic right ventricle;
      (2) RV group (n = 37): right dominant and hypoplastic left ventricle; and (3) BV
      group (n = 15): biventricular or indeterminate dominance. Perioperative major
      adverse events were collected based on the Society of Thoracic Surgeons database.
      The need for perioperative allogeneic blood transfusions also was determined. The
      mean age was 3.3+/-1.7 years and the mean weight was 13.6+/-4.0 kg. All patients
      had extracardiac lateral tunnel or conduit Fontan procedures. Sixty-nine of the
      patients (96%) underwent tracheal extubation in the operating room. Anesthesia,
      surgery, and CPB times were 326+/-68, 239+/-73, and 70+/-41 minutes,
      respectively. Eleven patients (15%) required allogeneic blood products
      intraoperatively, while 30 patients (42%) required allogeneic blood products
      during the perioperative period. Length of cardiac intensive care unit stay and
      hospital stay (median [IQR]) were 1 [1,2] and 12 [9,18] days, respectively. There
      was no mortality and no significant differences between groups in major
      postoperative complications, anesthetic or surgical variables. CONCLUSIONS: No
      difference in the immediate perioperative outcomes was noted based on ventricular
      morphology.

PMID- 27720491
TI  - Identification of Risk Factors Associated With Postoperative Acute Kidney Injury
      After Esophagectomy for Esophageal Cancer.
AB  - OBJECTIVE: To identify risks factors associated with acute kidney injury (AKI)
      after esophageal cancer surgery. DESIGN: This was a retrospective study. SETTING:
      Single academic center. PARTICIPANTS: Subjects with non-metastatic esophageal
      cancer. Patients were excluded if they were younger than 18 years and had missing
      data. MEASUREMENTS AND MAIN RESULTS: Primary outcome of the study was AKI
      according to AKI Network criteria. Demographic and perioperative variables were
      compared in patients with and without AKI. A multivariate Cox proportional model
      was used to assess the association between perioperative variables and AKI;
      p<0.05 was considered statistically significant. AKI was found in 107 (11.9%) of
      the 898 patients included in the study. The multivariate analysis also showed
      that BMI (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.03-1.11), number
      of comorbidities (OR 1.52, 95% CI 1.20-1.93, p = 0.001), and preoperative
      creatinine concentrations (OR 2.37, 95% CI 1.14-4.92, p = 0.02) were independent
      predictors for AKI. The use of dexamethasone was associated with a reduced risk
      for AKI. CONCLUSIONS: In support of previous reports in the literature, the
      authors found that AKI was not an uncommon complication after esophageal surgery.
      Obesity, cardiovascular comorbidities, and high preoperative concentrations were
      predictors of AKI. Dexamethasone administration during surgery appeared to have a
      protective effect. This finding opens an opportunity to further study in a
      randomized controlled trial the efficacy of dexamethasone in the prevention of
      AKI.

PMID- 27720492
TI  - Segmental Lung Isolation in a Postpneumonectomy Patient Undergoing Contralateral
      Lung Resection.

PMID- 27720493
TI  - Epidural Hematoma and Abscess Related to Thoracic Epidural Analgesia: A Single
      Center Study of 2,907 Patients Who Underwent Lung Surgery.
AB  - OBJECTIVE: To report the major complications (epidural hematoma and abscess) of
      postoperative thoracic epidural analgesia in patients who underwent lung surgery.
      DESIGN: Prospective, monocentric study. SETTING: A university hospital.
      PARTICIPANTS: All lung surgical patients who received postoperative thoracic
      epidural analgesia between November 2007 and November 2015. INTERVENTIONS:
      Thoracic epidural analgesia for patients who underwent lung surgery. MEASUREMENTS
      AND MAIN RESULTS: During the study period, data for 2,907 patients were recorded.
      The following 3 major complications were encountered: 1 case of epidural hematoma
      (0.34 case/1,000; 95% confidence interval 0.061-1.946), for which surgery was
      performed, and 2 cases of epidural abscesses (0.68 case/1,000; 95% confidence
      interval 0.189-2.505), which were treated medically. CONCLUSIONS: The risk range
      of serious complications was moderate; only the patient who experienced an
      epidural hematoma also experienced permanent sequelae.

PMID- 27720494
TI  - Assessment of Changes in Hemodynamics and Intrathoracic Fluid Using Electrical
      Cardiometry During Autologous Blood Harvest.
AB  - OBJECTIVE: To evaluate the effect of autologous blood harvest (ABH)-induced
      volume shifts using electrical cardiometry (EC) in patients with pulmonary artery
      hypertension secondary to left heart disease. DESIGN: Prospective, randomized,
      controlled trial. SETTING: A tertiary care hospital. PARTICIPANTS: The study
      comprised 50 patients scheduled to undergo heart valve replacement.
      INTERVENTIONS: Patients were divided randomly into 2 experimental groups that
      were distinguished by whether ABH was performed. Blood volume extracted in the
      test group was replaced simultaneously with 1:1 colloid (Tetraspan; B Braun
      Melsungen, Melsungen, Germany). Hemodynamic, respiratory, and EC-derived
      parameters were recorded at predefined set points (T1 [post-induction/pre-ABH]
      and T2 [20 minutes post-ABH]). MEASUREMENTS AND MAIN RESULTS: Withdrawal of 15%
      of blood volume in the ABH group caused significant reductions in thoracic fluid
      content (TFC) (-10.1% [-15.0% to -6.1%]); right atrial pressure (-23% [-26.6% to 
      17.6%]); mean arterial pressure (-12.6% [-22.2% to -3.8%]); airway pressures:
      (peak -6.2% [-11.7% to -2.8%] and mean -15.4% [-25.0% to -8.3%]); and oxygenation
      index (-10.34% [-16.4% to -4.8%]). Linear regression analysis showed good
      correlation between the percentage change in TFC after ABH and the percentage of
      change in right atrial pressure, stroke volume variation, autologous blood
      extracted, peak and mean airway pressures, and oxygen index. CONCLUSIONS: In
      addition to its proven role in blood conservation, therapeutic benefits derived
      from ABH include decongestion of volume-loaded patients, decrease in TFC, and
      improved gas exchange. EC tracks beat-to-beat fluid and hemodynamic fluctuations
      during ABH and helps in the execution of an early patient-specific, goal-directed
      therapy, allowing for its safe implementation in patients with pulmonary
      hypertension secondary to left heart disease.

PMID- 27720495
TI  - A New Modified Evans Blue Dye Test as Screening Test for Aspiration in
      Tracheostomized Patients.
AB  - OBJECTIVE: The authors assessed the diagnostic accuracy of a new modified Evans
      blue dye test (MEBDT) as a screening test for aspiration in tracheostomized
      patients. DESIGN: Monocentric retrospective study performed between October 2013
      and December 2015. SETTING: Anesthesia and Intensive Care Unit, Second University
      of Naples. PARTICIPANTS: Among 62 eligible patients, 5 were excluded. The
      authors' study population included 57 patients. INTERVENTIONS: Patients underwent
      both fiberoptic endoscopic examination of the swallow (FEES) and MEBDT to
      evaluate swallow. The MEBDT results were compared with those of FEES and the
      diagnostic accuracy of MEBDT was calculated using the FEES as the gold standard.
      MEASUREMENTS AND MAIN RESULTS: The authors found that both FEES and MEBDT were
      positive for aspiration in 40 patients (true-positive MEBDT); FEES and MEBDT were
      negative in 10 (true-negative MEBDT). On the other hand, FEES was positive with
      an MEBDT negative in 7 patients (false-negative MEBDT), and there were no FEES
      negative and MEBDT positive (false-positive MEBDT). MEBDT had a sensitivity,
      specificity, positive, and negative predicted value of 85%, 100%, 100%, and
      58.82%, respectively. CONCLUSIONS: MEBDT could be a supplementary diagnostic test
      for aspiration. Patients with positive MEBDT should not undergo oral feeding,
      while patients with negative MEBDT should undergo FEES before starting oral
      feeding.

PMID- 27720496
TI  - 2016 Nobel prize in medicine goes to Japanese scientist.

PMID- 27720498
TI  - Low-molecular-weight heparin for pregnancy complications.

PMID- 27720497
TI  - Low-molecular-weight heparin and recurrent placenta-mediated pregnancy
      complications: a meta-analysis of individual patient data from randomised
      controlled trials.
AB  - BACKGROUND: Placenta-mediated pregnancy complications include pre-eclampsia, late
      pregnancy loss, placental abruption, and birth of a small-for-gestational-age
      (SGA) neonate. These complications are leading causes of maternal, fetal, and
      neonatal morbidity and mortality in high-income countries. Affected women are at
      high risk of recurrence in subsequent pregnancies; however, effective strategies
      to prevent recurrence are absent. Findings from our previous study-level meta
      analysis suggested that low-molecular-weight heparin reduced the risk of
      recurrent placenta-mediated pregnancy complications. However, we identified
      significant heterogeneity in the results, possibly due to trial design or
      inclusion criteria. To identify which patients benefit from, and which outcomes
      are prevented by, low-molecular-weight heparin, we did an individual patient data
      meta-analysis. METHODS: We did a systematic review in May, 2013, which identified
      eight eligible randomised trials done between 2000 and 2013 of low-molecular
      weight heparin to prevent recurrent placenta-mediated pregnancy complications. We
      excluded studies on the basis of the wrong population, the study being ongoing,
      inability to confirm eligibility of participants, intervention stopped too early,
      and no response from the principal investigator. We requested individual patient
      data from the study authors for eligible women (women pregnant at the time of the
      study with a history of previous pregnancy that had been complicated by one or
      more of the following: pre-eclampsia, placental abruption, birth of an SGA
      neonate [<10th percentile], pregnancy loss after 16 weeks' gestation, or two
      losses after 12 weeks' gestation) and recoded, combined, and analysed the data
      for our meta-analysis. The primary outcome was a composite of early-onset (<34
      weeks) or severe pre-eclampsia, birth of an SGA neonate (<5th percentile), late
      pregnancy loss (>=20 weeks' gestation), or placental abruption leading to
      delivery, assessed on an intention-to-treat basis. We assessed risk of bias with
      the Cochrane Risk of Bias tool. This study is registered with PROSPERO, number
      CRD42013006249. FINDINGS: We analysed data from 963 eligible women in eight
      trials: 480 randomly assigned to low-molecular-weight heparin and 483 randomly
      assigned to no low-molecular-weight heparin. Overall, the risk of bias was not
      substantial enough to affect decisions regarding trial inclusion. Participants
      were mostly white (795/905; 88%) with a mean age of 30.9 years (SD 5.0) and
      403/963 (42%) had thrombophilia. In the primary analysis, low-molecular-weight
      heparin did not significantly reduce the risk of recurrent placenta-mediated
      pregnancy complications (low-molecular-weight heparin 62/444 [14%] versus no low
      molecular-weight heparin 95/443 (22%) absolute difference -8%, 95% CI -17.3 to
      1.4, p=0.09; relative risk 0.64, 95% CI 0.36-1.11, p=0.11). We noted significant
      heterogeneity between single-centre and multicentre trials. In subgroup analyses,
      low-molecular-weight heparin in multicentre trials reduced the primary outcome in
      women with previous abruption (p=0.006) but not in any of the other subgroups of
      previous complications. INTERPRETATION: Low-molecular-weight heparin does not
      seem to reduce the risk of recurrent placenta-mediated pregnancy complications in
      at-risk women. However, some decreases in event rates might have been too small
      for the power of our study to explore. FUNDING: Canadian Institutes of Health
      Research.

PMID- 27720499
TI  - Trajectories of health-related quality of life among family caregivers of
      individuals with dementia: A home-based caregiver-training program matters.
AB  - : To determine distinct courses of change in health-related quality of life
      (HRQoL) among family caregivers of individuals with dementia and how
      participating in a home-based caregiver-training program affects the probability
      of belonging to each course. Sixty three caregivers were in the intervention
      group, and 66 caregivers were in the control group of a single-blinded randomized
      clinical trial. Two distinct trajectories of HRQoL were identified: a well
      functioning trajectory and a poor-functioning trajectory. Caregivers who received
      the training program were more likely than those who did not have a well
      functioning trajectory of HRQoL over 18 months. This trajectory included bodily
      pain (b = 1.02, odds ratio [OR] = 2.76), general health perception (b = 1.28, OR
      = 3.60), social functioning (b = 1.12, OR = 3.05), vitality (b = 1.51, OR =
      4.49), general mental health (b = 1.08, OR = 2.94), and mental component summary
      (b = 1.27, OR = 3.55). Home-based caregiver training can be considered as part of
      the protocol for managing patients with dementia and their caregivers. TRIAL
      REGISTRATION NUMBER: NCT02667951.

PMID- 27720501
TI  - Putting negative attitudes on the agenda? Not Criminally Responsible Reform Act
      publicity and juror decision-making.
AB  - The current study examined the effect of publicity about Canada's recent Not
      Criminally Responsible (NCR) Reform Act - legislation surrounding accused in
      insanity cases that purportedly aims to enhance public safety - on juror decision
      making. In line with agenda-setting theory, we expected that NCR Reform Act
      publicity might reinforce certain fears about the insanity defence, dependent on
      whether it had either a positive or negative evaluative slant. Contrary to
      previous work on the insanity defence, participants in this study generally
      favoured a NCR verdict. The evaluative slant of the NCR publicity had no effect
      on verdict decisions or insanity defence attitudes, but there was a significant
      difference in participants' evaluations of the fairness of the Reform Act, such
      that those exposed to a positive or control article viewed the act as fairer than
      those exposed to a negative article. This study may aid future researchers in
      evaluating potential unintended consequences of the NCR Reform Act.

PMID- 27720500
TI  - Stimuli associated with the presence or absence of amphetamine regulate
      cytoskeletal signaling and behavior.
AB  - Drug-paired stimuli rapidly enlarge dendritic spines in the nucleus accumbens
      (NAcc). While increases in spine size and shape are supported by rearrangement of
      the actin cytoskeleton and facilitate the synaptic expression of AMPA-type
      glutamate receptors, it remains unclear whether drug-related stimuli can
      influence signaling pathways known to regulate these changes in spine morphology.
      These pathways were studied in rats trained on a discrimination learning paradigm
      using subcellular fractionation and protein immunoblotting to isolate proteins
      within dendritic spine compartments in the NAcc shell. An open field chamber was
      repeatedly associated with amphetamine in one group (Paired) and explicitly
      unpaired with amphetamine in another (Unpaired). Rats in a third group were
      exposed to the open field but never administered amphetamine (Control). When
      administered saline and returned to the open field one week later, Paired rats as
      expected displayed a conditioned locomotor response relative to rats in the other
      two groups. NAcc shell tissues were harvested immediately after this 30-minute
      test. Re-exposing Paired rats to the drug-paired excitatory context significantly
      decreased p-GluA2(S880), an effect consistent with reduced internalization of
      this subunit and increased spine proliferation in these rats. In contrast, re
      exposing Unpaired rats to the drug-unpaired context, capable of inhibiting
      conditioned responding in these animals, significantly decreased levels of both
      actin binding protein Arp2/3 and p-cofilin, consistent with spine volatility,
      shrinkage, and inhibition of spine proliferation in these rats. These findings
      show that contextual stimuli previously associated with either the presence or
      absence of amphetamine differentially regulate cytoskeletal signaling pathways in
      the NAcc.

PMID- 27720502
TI  - Focus on Autism Spectrum Disorder: Issues and Treatment Approaches.

PMID- 27720503
TI  - Severe Childhood Autism: The Family Lived Experience.
AB  - This research examined the experiences of families living with a child with
      severe autism. There is limited literature on the experiences of families when a
      child has severe autism as distinct from milder autism and includes the voices of
      multiple family members. Van Manen's phenomenological approach was used for data
      collection and analysis. This approach allowed for the use of innovative data
      sources, including unstructured individual and family interviews, observations,
      and family lifelines (a pictorial, temporal picture with comments of the families
      lives). This study included 29 interviews with 22 participants from 11 families.
      All data were creatively triangulated and interpreted. Six essential themes were
      identified. First, families experienced autism as mysterious and complex because
      it is an invisible and unpredictable condition with diagnostic challenges.
      Second, families described severe autism behaviors that often caused self-injury,
      harm to others and damaged homes. Third, profound communication deficits resulted
      in isolation between the family and child. Fourth, families discussed the
      unrelenting stress from lack of sleep, managing the child's developmental delays,
      coordinating and financing services, and concern for the child's future. Fifth,
      families described consequences of isolation from friends, school, the public,
      and health providers. Sixth, families portrayed their need for compassionate
      support and formed 'hybrid families' (nuclear, extended families and friends) to
      gain support. Study results can be utilized to educate nurses/other providers
      about the unique needs of families with children with severe autism and could
      influence health care policies to improve the care for families caring for
      children with severe autism.

PMID- 27720504
TI  - Some Reflections on Hypertension and Its Treatment.

PMID- 27720505
TI  - Comparison of the Efficacy and Safety of Fixed-dose S-Amlodipine/Telmisartan and
      Telmisartan in Hypertensive Patients Inadequately Controlled with Telmisartan: A
      Randomized, Double-blind, Multicenter Study.
AB  - PURPOSE: The objective of this study was to evaluate the efficacy and safety of
      the fixed-dose combination S-amlodipine plus telmisartan (S-AM/TEL) compared with
      TEL monotherapy in patients with hypertension inadequately controlled by TEL
      monotherapy. METHODS: this study was a randomized, multicenter, double-blind,
      parallel group, Phase III, 8-week clinical trial to compare the superiority of
      the S-AM/TEL 2.5/40-mg and S-AM/TEL 5/40-mg combinations with TEL 80-mg mono
      therapy. The primary end point was the change in the mean sitting diastolic blood
      pressure from baseline (week 0) after 8 weeks of therapy between treatment
      groups. FINDINGS: Of 325 patients screened, 183 were randomly assigned to 3
      groups (61 in the S-AM/TEL 2.5/40-mg group, 60 in the S-AM/TEL 5/40-mg group, and
      62 in the TEL 80-mg group). Mean (SD) age was 53.9 (7.5) years, and male patients
      comprised 87%. No significant differences were found among the 3 groups in
      baseline characteristics. The primary end points, the changes of mean (SD)
      diastolic blood pressure at week 8 from the baseline were -10.56 (7.23) mm Hg in
      the S-AM/TEL 2.5/40-mg group, -12.32 (9.23) mm Hg in the S-AM/TEL 5/40-mg group,
      and -2.44 (7.92) mm Hg in the TEL 80-mg group. Both the S-AM/TEL 2.5/40-mg group
      and the S-AM/TEL 5/40-mg group had a statistically superior hypotensive effect
      compared with the TEL 80-mg group (P < 0.0001 for both). For evaluation of the
      safety profile, the frequencies of adverse events (AEs) among the groups were
      also not significantly different (S-AM/TEL 2.5/40-mg group, 18.6%; S-AM/TEL 5/40
      mg group, 20%; and TEL 80-mg group, 22.6%), and the incidences of AEs were not
      different among the groups. The most common AEs were respiratory disorders,
      followed by headache, dizziness, and peripheral edema. IMPLICATIONS: Treatment
      with S-AM/TEL 2.5/40 mg and S-AM/TEL 5/40 mg was superior to increasing the TEL
      dose in terms of hypotensive effect in patients with hypertension inadequately
      controlled by TEL monotherapy. S-AM/TEL fixed-dose combinations are an effective
      and tolerable option for patients inadequately responding to TEL monotherapy and
      also a good option for improving patients' medication adherence.
      ClinicalTrials.gov identifier: NCT011426100.

PMID- 27720507
TI  - A pill at bedtime, and your heart is fine? Bedtime hypertension chronotherapy: An
      opportune and advantageous inexpensive treatment strategy.

PMID- 27720506
TI  - Effect of the premedication with oral clonidine on surgical comfort in patients
      undergoing fess due to advanced nasal polyposis: A randomized double blind
      clinical trial.
AB  - : OBJECTiVE: The objective of this randomized double blind study was to evaluate
      effect of the premedication with oral clonidine on blood pressure, cleaning of
      surgical site and bleeding in the ESS performed due to advanced NP. METHODS: A
      total of 52 patients who underwent functional endoscopic sinus surgery (FESS) due
      to Kennedy grade 4 nasal polyposis (NP) were included. Patients were randomized
      into two groups. Group 1 (n=26) received 0.2mg oral clonodine one hour before the
      operation in addition to standard anesthesia procedure. Group 2 (n=26) was
      administered standard anesthesia procedure alone. The amount of bleeding during
      surgery, cleaning of surgical site and surgeon's satisfaction were evaluated in
      comparison between the groups. RESULTS: The amount of bleeding and mean arterial
      pressure were significantly lower in the Group 1 compared to the Group 2. The
      cleaning of surgical site was found to be significantly better and surgeon's
      satisfaction significantly higher in the Group 1 than in the Group 2. Systolic,
      diastolic and mean arterial pressures during surgery were significantly lower in
      the Group 1 compared to the Group 2. CONCLUSION: Premedication with oral
      clonidine provides a clearer view of surgical site, reduces the amount of
      bleeding and significantly increases surgeon's satisfaction during the operation
      in FESS performed due to NP. Premedication with oral clonidine is a safe,
      inexpensive and effective methods in order to increase the surgical success and
      comfort and reduce complications in the FESS surgery.

PMID- 27720508
TI  - Prolonged prophylactic antibiotics with neurosurgical drains and devices: Are we
      using them? Do we need them?

PMID- 27720509
TI  - Health care workers' compliance to the My 5 Moments for Hand Hygiene: Comparison
      of 2 interventional methods.
AB  - This a prospective study comparing 2 interventions, incentive-based and audit
      feedback, for measuring compliance to the World Health Organization's My 5
      Moments for Hand Hygiene among nursing staff in a Lebanese tertiary care center
      over 21 weeks. Compliance was not achieved by default. The incentive-driven
      intervention helped boost compliance, and the audit-feedback intervention helped
      achieve high sustainability. Analysis of health care workers' behavior toward
      hand hygiene based on the My 5 Moments for Hand Hygiene concept is necessary to
      pinpoint difficulties in compliance.

PMID- 27720510
TI  - Anterolateral femoral bowing and loss of thigh muscle are associated with
      occurrence of atypical femoral fracture: Effect of failed tension band mechanism
      in mid-thigh.
AB  - BACKGROUND: The purpose of this study was to characterize anterolateral bowing of
      the femur using X-rays and muscular atrophy in the mid-thigh using computed
      tomography (CT) in patients with atypical femoral fractures (AFFs). We then
      compared the results with those of an intertrochanteric fracture to understand
      whether these measures act as causative factors of AFFs. METHODS: From January
      2009 to December 2015, 37 patients with complete AFF and 12 patients with
      incomplete AFF were enrolled in this study. Lateral femoral bowing, anterior
      femoral bowing, cross-sectional area (CSA), and attenuation coefficient of thigh
      muscles in the AFF group are measured and compare with those in the
      intertrochanteric fracture group. RESULTS: Lateral and anterior femoral bowing in
      the AFF group were significantly higher than those in the intertrochanteric
      fracture group. The level of fracture was found to be significantly associated
      with lateral and anterior femoral bowing (r = 0.569, r2 = 0.324, p < 0.001; r = 
      0.530, r2 = 0.281, p < 0.001, respectively). Total CSA and CSA of anterior and
      medial compartments were significantly lower in the AFF group (p < 0.05). The
      attenuation coefficient of the total thigh muscle and all three compartments in
      the AFF group were significantly lower than those in the intertrochanteric
      fracture group (p < 0.05). CONCLUSIONS: This study demonstrated that
      anterolateral femoral bowing and loss of thigh muscle were highly associated with
      the occurrence of AFFs.

PMID- 27720511
TI  - Prevalence of pincer, cam, and combined deformities in Japanese hip joints
      evaluated with the Japanese Hip Society diagnostic guideline for femoroacetabular
      impingement: A CT-based study.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) is thought to be associated with
      hip osteoarthritis. We investigated the prevalences of radiologic deformities of
      the pincer, cam, and their combinations in Japanese hip joints using computed
      tomography (CT) according to the Japanese Hip Society diagnostic guideline for
      FAI. METHODS: Multi-slice CT images were evaluated. Pincer deformities were
      defined as: type 1: center-edge angle (CE) >=40 degrees ; type 2: CE >= 30
      degrees  and acetabular roof obliquity <=0 degrees ; type 3: CE >= 25 degrees 
      and retroverted acetabulum. Cam deformities were defined as: type 1: CE >= 25
      degrees , alpha-angle >=55 degrees , and head-neck offset ratio <0.14; type 2: CE
      >= 25 degrees , alpha-angle >=55 degrees , and herniation pit positive; type 3:
      CE >= 25 degrees , alpha-angle >=55 degrees , and pistol grip deformity positive.
      RESULTS: We studied 128 hips. Pincer was detected in 35.9% (type 1, 12.5%; type
      2, 18.0%; type 3, 13.3%). Cam was detected in 24.2% (type 1, 23.4%; type 2, 7.8%;
      type 3, 10.9%). Combined deformities were detected in 10.2%. Type 3 pincer/type 1
      cam was the most frequent combined deformity compared with all combined
      deformities. All of the cam deformities, total combined deformities, and all
      radiological FAIs appeared significantly more often in men. CONCLUSIONS: When we
      used this guideline to diagnose FAI in a Japanese population, radiological FAI
      was common, and pincer deformities were more common than cam deformities. The
      most frequent seen pincer, cam, and combined deformities was type 2 pincer, type
      1 cam, and the combination of type 3 pincer/type 1 cam, respectively.

PMID- 27720513
TI  - Synergistic antidiabetic activity of Vernonia amygdalina and Azadirachta indica:
      Biochemical effects and possible mechanism.

PMID- 27720512
TI  - Incidence and survival of sebaceous carcinoma in the United States.
AB  - BACKGROUND: Information on risk factors, epidemiology, and clinical
      characteristics of sebaceous carcinoma (SC) is limited. OBJECTIVE: We sought to
      analyze trends in SC in the United States from 2000 through 2012. METHODS: We
      used data from the 18 registries of the Surveillance, Epidemiology, and End
      Results (SEER) Program from 2000 to 2012 to calculate the cause of death,
      relative frequencies/incidences, 5-/10-year Kaplan-Meier survival, hazard ratios,
      and incidence rates for SC. Each parameter was analyzed by age, location of
      occurrence (ocular/extraocular), race, sex, and SEER registry. RESULTS: Overall
      incidence was 0.32 (male) and 0.16 (female) per 100,000 person-years. Incidence
      significantly increased, primarily because of an increase among men. Incidence
      among whites was almost 3 times the rate among non-whites. Male sex (P < .0001),
      black race (P = .01), and extraocular anatomic location (P < .0001) were
      associated with significantly higher all-cause mortality. However, overall case
      specific mortality for SC decreased significantly. LIMITATIONS: Underregistration
      of patients in SEER registries, lack of verification of individual diagnoses, and
      low levels of staging data because of low stage-classification rate are
      limitations. CONCLUSIONS: The overall incidence of SC is increasing
      significantly. Male sex, black race, and extraocular occurrences are associated
      with significantly greater mortality.

PMID- 27720514
TI  - Do Changes in Patellofemoral Joint Offset Lead to Adverse Outcomes in Total Knee
      Arthroplasty With Patellar Resurfacing? A Radiographic Review.
AB  - BACKGROUND: Patellofemoral joint biomechanics contribute to anterior knee pain,
      instability, and dysfunction following total knee arthroplasty (TKA). Information
      about specific factors leading to anterior knee pain and dysfunction is currently
      limited. Changes in patellofemoral joint offset (PFO) refers to a mismatch
      between the preoperative and postoperative anteroposterior geometry of the
      patellofemoral joint. It remains unclear whether these changes lead to adverse
      outcomes in TKA. METHODS: A retrospective radiographic review of 970 knees pre
      TKA and post-TKA was completed to correlate the radiographic and clinical
      outcomes of changing the PFO using a posterior-stabilized single knee design with
      patellar resurfacing. RESULTS: A total of 970 patients were reviewed.
      Postoperatively, the anterior femoral offset, anteroposterior femoral size, and
      anterior patellar offset were changed in 40%, 60%, and 71% of knees,
      respectively, compared to preoperative values. The Western Ontario and McMasters
      Osteoarthritis Index total score as well as subscale scores for pain and function
      were not significantly affected by an increase or decrease in PFO. Similarly,
      Knee Society Scores and range of motion were not significantly affected.
      Increased anterior patellar offset was, however, associated with increased
      postoperative patellar tilt. Postoperative patellar tilt was not correlated with
      adverse patient satisfaction scores or loss of range of motion. CONCLUSION:
      Changes in PFO (decreased, maintained, or increased) are common post-TKA and are
      not associated with a difference in clinical outcomes. Increases in anterior
      patellar offset led to increased patellar tilt, which was not associated with
      adverse patient satisfaction scores.

PMID- 27720515
TI  - [Assessment of restrictive episiotomy use and impact on perineal tears in the
      Burgundy's Perinatal Network].
AB  - OBJECTIVES: To analyse episiotomy and perineal tears rates in Burgundy after
      French National College of Obstetricians and Gynecologists (CNGOF) guidelines in
      2005. MATERIALS AND METHOD: Multicenter retrospective study, between 2003-2005
      (period 1) et 2012-2014 (period 2), conducted on singletons vaginal deliveries,
      in cephalic presentation from 37 weeks. We compared the episiotomy rate (ER), and
      perineal lesions in normal deliveries (ND) and instrumental deliveries (ID)
      between the two periods. RESULTS: A total of 74,268 women were included. The
      overall ER significantly decreased from 35.8 to 16.7% (P<0.01), without
      increasing third degree perineal tears (0.73% vs. 0.66%) or fourth degree (0.14%
      vs 0.14%). First degree perineal tears rose (42.1% vs 17.6%, P<0.001), second
      degree decreased (13.5% vs 20.5%, P<0.001). ER decreased whatever the level of
      motherhood, healthcare ward, vaginal delivery type, or the instrument used.
      CONCLUSION: Our study found a strong impact in Burgundy of the French guidelines
      for the practice of restrictive episiotomy for both ND and for ID without
      increasing sphincter tears and in decreasing spontaneous morbidity.

PMID- 27720516
TI  - [Pregnancy in women with spinal cord injuries: State of knowledge].
AB  - OBJECTIVES: Updating knowledge of health professionals about pregnant women with
      spinal cord injuries. Development of maternity hospitals to make them accessible
      to spinal cord injured pregnant women to improve their care in pre-, per- and
      post-partum. METHODS: Cross-sectional declarative study based on a questionnaire
      distributed to health professionals in the maternity hospital of the University
      Hospital of Nantes and liberal midwives of Nantes conurbation, based on their
      knowledge, their difficulties and their expectations for obstetrical care for
      spinal cord injured women. An inventory was carried out in parallel at the
      maternity hospital of the University Hospital of Nantes. RESULTS: Seventy-two
      percent of health professionals surveyed rated their level of knowledge on spinal
      cord injuries insufficient or even non-existent. Among the professionals, 84.8%
      said they encountered difficulties to take care of spinal cord injured women. The
      main cited difficulty relates to unsuitable equipment or premises, obstacle
      indeed found during the inventory made on the maternity hospital. CONCLUSION:
      Several proposals are being considered, including specific trainings, the
      execution of a management protocol for spinal cord injured women, the
      establishment of a situation's form of handicap, the layout of the maternity
      hospitals premises, and finally, the creation of reference's centers in the
      region to optimize the follow-up of these patients.

PMID- 27720517
TI  - [DAME trial: What consequences for our clinical practice?]

PMID- 27720518
TI  - Novel Interest About Cardiac Variation of Internal Jugular Vein for the
      Evaluation of the Hemodynamics.

PMID- 27720519
TI  - Segmentation of Skin Tumors in High-Frequency 3-D Ultrasound Images.
AB  - High-frequency 3-D ultrasound imaging is an informative tool for diagnosis,
      surgery planning and skin lesion examination. The purpose of this article was to
      describe a semi-automated segmentation tool providing easy access to the extent,
      shape and volume of a lesion. We propose an adaptive log-likelihood level-set
      segmentation procedure using non-parametric estimates of the intensity
      distribution. The algorithm has a single parameter to control the smoothness of
      the contour, and we describe how a fixed value yields satisfactory segmentation
      results with an average Dice coefficient of D = 0.76. The algorithm is
      implemented on a grid, which increases the speed by a factor of 100 compared with
      a standard pixelwise segmentation. We compare the method with parametric methods
      making the hypothesis of Rayleigh or Nakagami distributed signals, and illustrate
      that our method has greater robustness with similar computational speed.
      Benchmarks are made on realistic synthetic ultrasound images and a data set of
      nine clinical 3-D images acquired with a 50-MHz imaging system. The proposed
      algorithm is suitable for use in a clinical context as a post-processing tool.

PMID- 27720520
TI  - Three-Dimensional Ultrasound-Guided Real-Time Midline Epidural Needle Placement
      with Epiguide: A Prospective Feasibility Study.
AB  - Current 2-D ultrasound technology is unable to perform a midline neuraxial needle
      insertion under real-time ultrasound guidance using a standard needle and without
      an assistant. The aim of the work described here was to determine the feasibility
      of a new technology providing such capability, starting with a study evaluating
      the selected puncture site. A novel 3-D ultrasound imaging technique was designed
      using thick-slice rendering in conjunction with a custom needle guide (3DUS +
      Epiguide). A clinical feasibility study evaluated the ability of 3DUS + Epiguide
      to identify the epidural needle puncture site for a midline insertion in the
      lumbar spine. We hypothesized that (i) the puncture site identified by 3DUS +
      Epiguide was within a 5-mm radius from the site chosen by standard palpation, and
      (ii) the difference between the two puncture sites was not correlated to the
      patient characteristics age, weight, height, body mass index and gestational age.
      The mean (+/-standard deviation) distances between puncture sites determined by
      3DUS + Epiguide and palpation were 3.1 (+/-1.7) mm and 2.8 (+/-1.3) mm, for the
      L2-3 and L3-4 interspaces of 20 patients, respectively. Distances were comparable
      to intra-observer variability, indicating the potential for a thick-slice
      rendering of 3-D ultrasound along the Epiguide trajectory to select the puncture
      site of a midline neuraxial needle insertion. The long-term potential benefits of
      this system include increased efficiency and use of anesthesia, and a reduction
      in the frequency and severity of the complications from incorrect needle
      insertions. Epidural success in the most difficult cases (e.g., the obese) will
      be the focus of future work.

PMID- 27720521
TI  - A Novel Elastographic Frame Quality Indicator and its use in Automatic
      Representative-Frame Selection from a Cine Loop.
AB  - This study was aimed at developing a method for automatically selecting a few
      representative frames from several hundred axial-shear strain elastogram frames
      typically obtained during freehand compression elastography of the breast in
      vivo. This may also alleviate some inter-observer variations that arise at least
      partly because of differences in selection of representative frames from a cine
      loop for evaluation and feature extraction. In addition to the correlation
      coefficient and frame-average axial strain that have been previously used as
      quality indicators for axial strain elastograms, we incorporated the angle of
      compression, which has unique effects on axial-shear strain elastogram
      interpretation. These identified quality factors were computed for every frame in
      the elastographic cine loop. The algorithm identifies the section having N
      contiguous frames (N = 10) that possess the highest cumulative quality scores
      from the cine loop as the one containing representative frames. Data for total of
      40 biopsy-proven malignant or benign breast lesions in vivo were part of this
      study. The performance of the automated algorithm was evaluated by comparing its
      selection against that by trained radiologists. The observer- identified frame
      that consisted of a sonogram, axial strain elastogram and axial-shear strain
      elastogram was compared with the respective images in the frames of the algorithm
      identified section using cross-correlation as a similarity measure. It was
      observed that there was, on average (~standard deviation), 82.2% (~2.2%), 83.4%
      (~3.8%) and 78.4% (~3.6%) correlation between corresponding images of the
      observer-selected and algorithm-selected frames, respectively. The results
      indicate that the automatic frame selection method described here may provide an
      objective way to select a representative frame while saving time for the
      radiologist. Furthermore, the frame quality metric described and used here can be
      displayed in real time as feedback to guide elastographic data acquisition and
      for training purposes.

PMID- 27720522
TI  - Fully Automated Muscle Ultrasound Analysis (MUSA): Robust and Accurate Muscle
      Thickness Measurement.
AB  - Musculoskeletal ultrasound imaging allows non-invasive measurement of skeletal
      muscle thickness. Current techniques generally suffer from manual operator
      dependency, while all the computer-aided approaches are limited to be semi
      automatic or specifically optimized for a single muscle. The aim of this study
      was to develop and validate a fully automatic method, named MUSA (Muscle
      UltraSound Analysis), for measurement of muscle thickness on longitudinal
      ultrasound images acquired from different skeletal muscles. The MUSA algorithm
      was tested on a database of 200 B-mode ultrasound images of rectus femoris,
      vastus lateralis, tibialis anterior and medial gastrocnemius. The automatic
      muscle thickness measurements were compared to the manual measurements obtained
      by three operators. The MUSA algorithm achieved a 100% segmentation success rate,
      with mean differences between the automatic and manual measurements in the range
      of 0.06-0.45 mm. MUSA performance was statistically equal to the operators and
      its measurement accuracy was independent of the muscle thickness value.

PMID- 27720523
TI  - Reply: Novel Interest About Cardiac Variation of Internal Jugular Vein for the
      Evaluation of the Hemodynamics.

PMID- 27720524
TI  - Depression and Functional Status Among African American Stroke Survivors in
      Inpatient Rehabilitation.
AB  - PURPOSE: To examine the prevalence of poststroke depression (PSD) among African
      American stroke survivors and the association of depression with functional
      status at inpatient rehabilitation facility (IRF) discharge. METHODS: Secondary
      data analysis was conducted of a patient cohort who received care at 3 IRFs in
      the United States from 2009 to 2011. Functional status was measured by the
      Functional Independence Measure (FIM). Multiple linear regression models were
      used to examine associations of PSD and FIM motor and cognitive scores. RESULTS:
      Of 458 African American stroke survivors, 48.5% were female, 84% had an ischemic
      stroke, and the mean age was 60.8 +/- 13.6 years. Only 15.4% (n = 71) had
      documentation of PSD. Bivariate analyses to identify factors associated with
      depression identified a higher percentage of patients with depression than
      without who were retired due to disability (17.1% versus 11.6%) or employed
      (31.4% versus 19.6%) prestroke (P = .041). Dysphagia, cognitive deficits, and a
      lower admission motor FIM score were also significantly more common among those
      with depression. There was no significant relationship between depression and
      functional status after adjusting for patient characteristics. CONCLUSIONS: In
      this study, 15% of the African Americans who received rehabilitation after a
      stroke had documentation of PSD but this was not associated with functional
      status at discharge.

PMID- 27720525
TI  - Predictive Value of Modifications of the Prehospital Rapid Arterial Occlusion
      Evaluation Scale for Large Vessel Occlusion in Patients with Acute Stroke.
AB  - BACKGROUND: Prehospital clinical scales to identify patients with acute stroke
      with a large vessel occlusion (LVO) and direct them to an endovascular-capable
      stroke center are needed. We evaluated whether simplification of the Rapid
      Arterial oCclusion Evaluation (RACE) scale, a 5-item scale previously validated
      in the field, could maintain its high performance to identify patients with LVO.
      METHODS: Using the original prospective validation cohort of the RACE scale, 7
      simpler versions of the RACE scale were designed and retrospectively recalculated
      for each patient. National Institutes of Health Stroke Scale score and proximal
      LVO were evaluated in hospital. Receiver operating characteristic analysis was
      performed to test performance of the simplified versions to identify LVO. For
      each version, the threshold with sensitivity closest to the original scale (85%)
      was used, and the variation in specificity and correct classification were
      assessed. RESULTS: The study included 341 patients with suspected stroke; 20% had
      LVO. The 7 simpler versions of the RACE scale had slightly lower area under the
      curve for detecting LVO because of lower specificity at the chosen sensitivity
      level. Correct classification rate decreased 9% if facial palsy was simplified or
      if eye or gaze deviation was removed, and decreased 4.5% if the aphasia or
      agnosia cortical sign was removed. CONCLUSIONS: We recommend the original RACE
      scale for prehospital assessment of patients with suspected stroke for its ease
      of use and its high performance to predict the presence of a LVO. The use of
      simplified versions would reduce its predictive value.

PMID- 27720526
TI  - Histological Examination of Trousseau Syndrome-Related Thrombus Retrieved Through
      Acute Endovascular Thrombectomy: Report of 2 Cases.
AB  - The mechanism of thrombus formation in Trousseau syndrome remains unclear. The
      purpose of this study was to investigate specific pathological findings of the
      thrombi in Trousseau syndrome. The authors report on 2 cases of thrombi in
      Trousseau syndrome from large cerebral vessels removed by endovascular therapy
      and compared with thrombi in atherosclerosis or cardiac embolism. The first
      patient, a 67-year-old man, was transferred to our hospital for sudden onset
      consciousness disturbance and tetraparesis. He had been diagnosed with stage IV
      lung cancer. The magnetic resonance (MR) angiography demonstrated basilar artery
      occlusion. An endovascular thrombectomy was performed. The second patient, an 84
      year-old woman, was transferred to our hospital for sudden onset motor aphasia
      and right-sided motor weakness. She has a history of stage IV pancreatic body
      cancer. The MR angiography demonstrated left middle cerebral artery occlusion. An
      endovascular thrombectomy was performed for the floating thrombus. Macroscopic
      findings of retrieved thrombi were observed immediately after thrombectomy. The
      thrombi in Trousseau syndrome were white in color and solid against manual
      compression, whereas thrombi from other causes were red and fragile. In terms of
      microscopic findings, the thrombi in Trousseau syndrome mainly contained fibrin.
      On the other hand, thrombi associated with atherosclerosis or cardiac embolism
      had smaller area of fibrin with a considerable amount of red and white blood
      cells. The thrombi in Trousseau syndrome, which caused occlusion of large
      cerebral vessel, almost exclusively consisted of fibrin.

PMID- 27720527
TI  - Climate influence on juvenile European sea bass (Dicentrarchus labrax, L.)
      populations in an estuarine nursery: A decadal overview.
AB  - Estuarine systems support the life cycle stages of commercially important marine
      fish and are influenced by large and local-scale climatic patterns. In this
      study, performed in the Mondego estuary, Portugal, we used an 11-year database
      (2003-2013) for analyzing the variability in the population of a marine juvenile
      migrant fish, the European sea bass Dicentrarchus labrax, regarding changes in
      abundance, population structure, growth rates, secondary production and annual
      day of peak abundance. Higher densities and production occurred in 2003, but no
      differences in 0-group growth could be observed. In order to detect change points
      in both biological and climatic data, the cumulative sum (CUSUM) of the
      deviations from the mean for the 2003-2013 period were determined for each
      parameter. The relationship between large and local-scale drivers and 0-group
      biological attributes were evaluated using a Spearman rank correlation analysis
      of CUSUM of biological and environmental data, considering the correspondent
      yearly values and with a time-lag of 1 year. The North Atlantic Oscillation (NAO)
      index, sea surface temperature (SST) and their respective winter values were
      tested as large-scale factors, while river runoff, salinity and estuarine water
      temperature were considered as local climate patterns. The significant factors
      explaining D. labrax 0-group abundance and production were salinity and the NAO,
      the latter being also a significant predictor considering the 1-year lag. The NAO
      with 1-year lag was also positively correlated with the day of peak abundance.
      The early stages of European sea bass were demonstrated to have a climate
      dependent life cycle, controlled by variations in both large-scale climatic
      patterns and local features. In southern European marine populations, the effects
      of the NAO seem less direct, and dependent on the magnitude of its expressions
      and on the time scale considered.

PMID- 27720528
TI  - Distinct community dynamics at two artificial habitats in a recreational marina.
AB  - Man-made facilities along coastlines modify water circulation and sedimentation
      dynamics which can affect the structure of marine benthic and pelagic
      communities. To test how environmental heterogeneity associated with a
      recreational marina affects the structure of the fouling community and the
      benthic-pelagic link, we conducted an experiment in which predation effects on
      recruitment and community structure were assessed in two artificial habitats:
      inside the marina, an area of calm waters and often disturbed by boating
      activity, and the breakwater, a more hydrodynamic area. Using visual censuses and
      video footages we also described the predation pressure and the identity of
      predators on the two areas. Inside the marina, the recruitment of ascidians and
      serpulids, but not of bryozoans, was restricted in some occasions, possibly due
      to reduced water circulation. Predation, mainly by the silver porgy fish Diplodus
      argenteus, reduced the survivor of didemnid ascidians on both areas, but
      predation intensity was 40 times higher in the breakwater than inside the marina.
      While the two artificial habitats did not necessarily support distinct
      communities, low recruitment coupled to weak predation inside the marina, a less
      dynamic environment, likely imply lower resilience and more susceptibility to
      disturbance.

PMID- 27720529
TI  - Publication Rates of Podium Versus Poster Presentations at the Arthroscopy
      Association of North America Meetings 2008-2012.
AB  - PURPOSE: To analyze the publication rate of poster and podium presentations at
      Arthroscopy Association of North America (AANA) annual meetings from 2008 to
      2012. METHODS: An online search using PubMed and Google Scholar for all published
      manuscripts associated with abstracts presented from 2008 to 2012 AANA annual
      meetings was performed. Abstracts were classified by presentation type (poster vs
      podium), and the journal and publication date were recorded for all published
      abstracts. Descriptive statistics, logistic regression, and Fisher's exact tests
      were performed, with P < .05 considered significant. RESULTS: A total of 1,508
      abstracts were submitted to AANA annual meetings from 2008 to 2012, with 976
      abstracts accepted for presentation (65% overall acceptance rate). There were 328
      podium (22% acceptance rate) and 648 poster (43% acceptance rate) presentations.
      Of the 976 accepted abstracts, 479 (49%) were published within 3 years in peer
      reviewed journals. The overall publication rates for podium and poster
      presentations were 59% (n = 193) and 44% (n = 286), respectively. Podium
      presentations were significantly more likely to be published within 3 years
      compared with poster presentations (P < .0001; odds ratio 1.8095, confidence
      interval 1.3826-2.3682). There were no differences in time to publication between
      podium and poster presentations (1.3 +/- 1.2 vs 1.1 +/- 1.3 years, P = .0633).
      Over the 5-year study period, the overall abstract acceptance rate (P < .0001)
      and the rate of abstracts accepted for poster presentation (P < .0001) increased
      significantly over time, whereas there was no increase in the rate of abstracts
      accepted for podium presentation (P = .5638). The most common journals of
      publication were Arthroscopy (n = 157, 32.7%) followed by American Journal of
      Sports Medicine (n = 93, 19.4%). CONCLUSIONS: The overall publication rate of
      abstracts presented at AANA annual meetings is 49%, with podium presentations 1.8
      times more likely to be published than poster presentations. The overall abstract
      acceptance rate and the rate of abstracts accepted for poster presentation
      increased significantly over time, whereas there was no significant increase in
      the rate of abstracts accepted for podium presentation. CLINICAL RELEVANCE: The
      publication rates of abstracts presented at the AANA annual meetings demonstrate
      the meetings' impact and importance to the advancement of the scientific
      literature.

PMID- 27720530
TI  - Reply to Che-Kai Tsao, Matthew D. Galsky, and William K. Oh's Platinum Opinion.
      Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer: Urgent Need To
      Minimize The Risk Of Neutropenic Fever. Eur Urol 2016;70:707-708.

PMID- 27720532
TI  - Setting an Agenda for Assessment of Health-related Quality of Life Among Men with
      Prostate Cancer on Active Surveillance: A Consensus Paper from a European School
      of Oncology Task Force.
AB  - BACKGROUND: Literature on the health-related quality of life (HRQoL) for men with
      localized prostate cancer (PCa) on active surveillance (AS) shows a need for
      methodological guidance regarding HRQoL issues and how to address them.
      OBJECTIVE: The European School of Oncology Task Force (ESO TF) aimed to identify
      a core set of research questions and related measures to include in AS HRQoL
      studies. DESIGN, SETTING, AND PARTICIPANTS: A modified Delphi study was used to
      reach consensus on AS HRQoL research topics and tools between 2014 and 2015. Data
      were collected by engaging a multidisciplinary team of 15 experts. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: An open-ended questionnaire was used to
      collect information from ESO TF members regarding issues in AS HRQoL research.
      Then a structured questionnaire was used to collect ratings on the
      usefulness/importance of different AS HRQoL aspects. Items that >=80% of ESO TF
      members rated as useful/important were retained. Items with a 50-80% rating were
      discussed to reach final agreement. RESULTS AND LIMITATIONS: Six main research
      questions concerning the selection of outcome measures, measurement tools, and
      comparison groups were identified as relevant. The core set of measures
      identified were related to individual characteristics, psychological dimensions;
      decision-making-related issues, and physical functioning. The multidisciplinary
      expertise of ESO TF members was a significant asset, even if bringing different
      backgrounds to the discussion table represented a challenge. CONCLUSIONS: HRQoL
      measures have to be sensitive to the specific needs of men on AS. The definition
      of HRQoL outcomes will enhance a broader understanding of the HRQoL of men on AS
      and sustain patient-centered medicine. PATIENT SUMMARY: An international panel
      agreed on a set of health-related quality-of-life aspects to be assessed among
      men on active surveillance for prostate cancer. Valid relevant questionnaires
      were identified. The experts' indications lay a foundation for future research
      and clinical practice.

PMID- 27720531
TI  - Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer:
      A Prospective Multicentric Hemiablation Study of 111 Patients.
AB  - BACKGROUND: Up to a third of patients with localized prostate cancer have
      unilateral disease that may be suitable for partial treatment with hemiablation.
      OBJECTIVE: To evaluate the ability of high intensity focused ultrasound (HIFU) to
      achieve local control of the tumor in patients with unilateral localized prostate
      cancer. DESIGN, SETTING, AND PARTICIPANTS: The French Urological Association
      initiated a prospective IDEAL multi-institutional study (2009-2015), to evaluate
      HIFU-hemiablation as a primary treatment. INTERVENTION: Multiparametric magnetic
      resonance imaging and biopsy were used for unilateral cancer diagnosis and
      control, and HIFU-hemiablation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Primary: absence of clinically significant cancer (CSC) on control biopsy at 1 yr
      (CSC: Gleason score >= 7 or cancer core length>3mm regardless of grade or > 2
      positive cores). Secondary: presence of any cancer on biopsy, biochemical
      response, radical treatment free survival, adverse events, continence (no pad),
      erectile function (International Index of Erectile Function-5 >= 16), and quality
      of life (European Organization for Research and Treatment of Cancer QLQ-C28)
      questionnaires. RESULTS AND LIMITATIONS: One hundred and eleven patients were
      treated (mean age: 64.8 yr [standard deviation 6.2]; mean prostate-specific
      antigen: 6.2 ng/ml [standard deviation 2.6]; 68% low risk, 32% intermediate
      risk). Of the 101 patients with control biopsy, 96 (95%) and 94 (93%) had no CSC
      in the treated and contralateral lobes, respectively. Mean prostate-specific
      antigen at 2 yr was 2.3 ng/ml (standard deviation 1.7). The radical treatment
      free survival rate at 2 years was 89% (radical treatments: six radical
      prostatectomies, three radiotherapies, and two HIFU). Adverse events were Grade 3
      in 13%. At 12 mo continence and erectile functions were preserved in 97% and 78%.
      No significant decrease in quality of life score was observed at 12 mo. One
      limitation is the number of low-risk patients included in this study.
      CONCLUSIONS: At 1 yr, HIFU-hemiablation was efficient with 95% absence of
      clinically significant cancer associated with low morbidity and preservation of
      quality of life. Radical treatment-free survival rate was 89% at 2 yr. PATIENT
      SUMMARY: This report shows that high intensity focused ultrasound half-gland
      treatment of unilateral prostate cancer provides promising results with high
      cancer control and low morbidity.

PMID- 27720533
TI  - Methodological Considerations for Early-phase Development of Immune Checkpoint
      Inhibitors in Urothelial Bladder Cancer.

PMID- 27720535
TI  - Je le pansai, Dieu le guerit.

PMID- 27720534
TI  - Systematic Review on the Fate of the Remnant Urothelium after Radical Cystectomy.
AB  - CONTEXT: Urothelial carcinoma is considered a pan-urothelial disease. As such,
      the remnant urothelium in the upper urinary tract and urethra following radical
      cystectomy (RC) remains at risk for secondary urothelial tumors (SUTs).
      OBJECTIVE: To describe the incidence, diagnosis, treatment, and outcomes of
      patients with SUTs after RC. EVIDENCE ACQUISITION: A systematic search was
      conducted using PubMed database according to Preferred Reporting Items for
      Systematic Reviews and Meta-analyses guidelines to identify studies between 1970
      and 2016 reporting on malignant diseases of the urothelium after RC for bladder
      cancer. The search strategy separated between upper and lower tract urothelial
      tumors. EVIDENCE SYNTHESIS: Of a total of 1069 studies, 57 were considered for
      evidence synthesis. SUTs occured in approximately 4-10% of patients after RC.
      Carcinoma in situ of the bladder, a history of nonmuscle invasive bladder cancer,
      and tumor involvement of the distal ureter are the strongest risk factors for
      secondary upper tract tumors. Risk factors for secondary urethral tumors
      represent urothelial malignancy in the prostatic urethra/prostate and bladder
      neck (in women), nonorthotopic diversions, and positive findings on permanent
      sections. The majority of patients (84%) with SUTs, presented with urothelial
      recurrence without evidence of metastasis. Of those, 84.0% were treated with
      surgery, 10.5% with systemic chemotherapy and/or radiotherapy, and 5.6% with
      topical chemotherapy and/or immunotherapy. After a median follow-up of 91 mo
      (range: 26-155), 65.9% of patients died of disease and 21.5% died of other
      causes. Detection and treatment of SUTs at an asymptomatic stage can reduce the
      risks of cancer-specfific and overall mortality by 30%. A limitation of the study
      is that the available data were retrospective. CONCLUSIONS: SUTs are rare
      oncological events and most patients have an adverse prognosis despite absence of
      distant disease at diagnosis. Therefore, surveillance of the remnant urothelium
      should be implemented for patients with histological features of panurothelial
      disease as it may improve timely detection and treatment. PATIENT SUMMARY:
      Secondary tumors of the renal pelvis, ureters, and urethra occur in approximately
      4-10% of patients after radical removal of the bladder for bladder cancer. These
      patients' prognoses are reduced, likely due to delayed diagnosis. Therefore,
      routine surveillance might be important to detect tumors at an early stage.

PMID- 27720536
TI  - Pathophysiology and Contributing Factors in Postprostatectomy Incontinence: A
      Review.
AB  - CONTEXT: The incidence and awareness of postprostatectomy incontinence (PPI) has
      increased during the past few years, probably because of an increase in prostate
      cancer surgery. Many theories have been postulated to explain the pathophysiology
      of PPI. OBJECTIVE: The current review scrutinizes various pathophysiologic
      mechanisms underlying the occurrence of PPI. EVIDENCE ACQUISITION: A search was
      conducted on PubMed and EMBASE for publications on PPI. The primary search
      returned 2518 publications. Animal and basic research studies, letters,
      publications on prostatectomy for benign reasons, pathology of prostatic
      carcinoma, radiotherapy and hormone therapy of prostatic carcinoma, and review
      articles were all used as criteria for exclusion from the study. A total of 128
      publications were selected for final analysis. EVIDENCE SYNTHESIS: Neuromuscular
      anatomic elements and pelvic support are known to influence PPI as evidenced by
      multiple publications. A number of non-anatomic and surgical elements have been
      postulated as contributing factors to PPI. Biological factors and preoperative
      parameters include: functional bladder changes, age, body mass index (BMI), pre
      existing lower urinary tract symptoms (LUTS), prostate size, and oncologic
      factors. Multiple studies reported the impact of specific anatomic/surgical
      factors, including fibrosis, shorter membranous urethral length (MUL),
      anastomotic stricture, damage to the neurovascular bundle, and extensive
      dissection, all of which have a negative impact on the continence status of
      patients following radical prostatectomy (RP). Investigation of the impact of
      techniques to spare the bladder neck and additional procedures to reconstruct the
      posterior or anterior support structures (eg, the Rocco stitch) on continence
      status is ongoing. CONCLUSIONS: Anatomic support and pelvic innervation appear to
      be important factors in the etiology of PPI. Biological/preoperative factors
      including greater age at time of surgery, pre-existing LUTS, high BMI, shorter
      MUL, and functional bladder changes have a negative impact on continence after
      RP. Extensive dissection during surgery, damage to the neurovascular bundle, and
      postoperative fibrosis also have a substantial negative impact on the continence
      status of men undergoing RP. Sparing of the bladder neck and anterior fixation of
      the bladder-urethra anastomosis are associated with better continence rates.
      There is still debate about whether posterior pelvic reconstruction leads to
      better postoperative continence rates. PATIENT SUMMARY: Radical prostatectomy is
      an oncologic procedure and thus requires removal of the entire prostate gland and
      seminal vesicles, ideally with negative surgical margins. This sometimes results
      in urinary incontinence. The factors contributing to urinary incontinence are
      explained in this article.

PMID- 27720538
TI  - Reply to Glen Denmer Santok and Koon Ho Rha's Letter to the Editor re: Par
      Stattin, Fredrik Sandin, Frederik Birkebaek Thomsen, et al. Association of
      Radical Local Treatment with Mortality in Men with Very High-risk Prostate
      Cancer: A Semiecologic, Nationwide, Population-based Study. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2016.07.023.

PMID- 27720539
TI  - Oligoantiemesis: A Premature Neologism for an Intervention Insufficiently
      Substantiated in the Emergency Setting.

PMID- 27720537
TI  - Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT
      Trial.
AB  - BACKGROUND: Early detection and treatment of asymptomatic men with advanced and
      high-risk prostate cancer (PCa) may improve survival rates. OBJECTIVE: To
      determine outcomes for men diagnosed with advanced PCa following prostate
      specific antigen (PSA) testing who were excluded from the ProtecT randomised
      trial. DESIGN, SETTING, AND PARTICIPANTS: Mortality was compared for 492 men
      followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK
      Anglia Cancer Network (ACN) and with a matched subset from the ACN. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: PCa-specific and all-cause mortality were
      compared using Kaplan-Meier analysis and Cox's proportional hazards regression.
      RESULTS AND LIMITATIONS: Of the 492 men excluded from the ProtecT cohort, 37 (8%)
      had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The
      median PSA was 17MUg/l. Treatments included radical prostatectomy (RP; n=54;
      11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122;
      25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa
      specific deaths (10%), of whom 14 men had received radical treatment (5%); and
      129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64
      (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all
      causes. ProtecT men had a 45% lower risk of death from PCa compared to matched
      cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but
      mortality was similar in those treated radically. The nonrandomised design is a
      limitation. CONCLUSIONS: Men with PSA-detected advanced PCa excluded from ProtecT
      and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men
      who underwent nonradical treatment, the ProtecT group had a lower rate of PCa
      death. Early detection through PSA testing, leadtime bias, and group
      heterogeneity are possible factors in this finding. PATIENT SUMMARY: Prostate
      cancer that has spread outside the prostate gland without causing symptoms can be
      detected via prostate-specific antigen testing and treated, leading to low rates
      of death from this disease.

PMID- 27720541
TI  - The pathways of genetic transformation in cholangiocarcinogenesis.
AB  - Cholangiocarcinoma (CCA) is an aggressive malignancy that originates from the
      epithelial cells of the biliary duct system. Depending on the anatomical
      location, CCA can be considered extrahepatic (eCCA) or intrahepatic (iCCA) (1).
      Two thirds of CCAs involve the extrahepatic biliary system, whereas the rest are
      confined within the liver parenchyma, beyond the secondary biliary radicals (2).
      Due to its biological aggressiveness and difficulty in diagnosis, the majority of
      patients with CCA are unresectable at presentation and the overall 5-year
      survival is approximately five percent (4). This article focuses on the genetic
      and epigenetic alterations present in cholangiocarcinomas, their occasional
      relationship to external stimuli, and with an emphasis on those unanswered
      questions about cholangiocarcinogenesis and future directions in the
      comprehension of epigenetic DNA methylation in patients with CCA.

PMID- 27720540
TI  - Best Clinical Practice: Current Controversies in Pulmonary Embolism Imaging and
      Treatment of Subsegmental Thromboembolic Disease.
AB  - BACKGROUND: Pulmonary embolism (PE) affects >600,000 patients per year in the
      United States. Evaluation includes clinical decision rules, laboratory tests, and
      several imaging modalities. The diagnosis of PE has risen in recent years,
      particularly subsegmental PE (SSPE). Controversy exists concerning the diagnosis
      and treatment of these lesions. OBJECTIVE: We sought to provide emergency
      physicians with a review of the controversies surrounding PE testing and the
      diagnosis and treatment of SSPE. DISCUSSION: With the rise of computed tomography
      (CT) testing for PE, diagnosis has increased. Providers often omit risk
      stratification in favor of D-dimer or imaging, which does not have literature
      support. The detection of PE has risen by 80%, and this increased testing is
      associated with several risks, including contrast reaction, nephropathy, and
      increased radiation. SSPE diagnosis has risen with improved imaging technology,
      but the literature shows low interobserver agreement with diagnosis of true SSPE.
      Studies disagree on the clinical significance and dangers of this PE subset. The
      American College of Chest Physicians 2016 guidelines recommend withholding
      anticoagulation for SSPE with low risk for recurrent thrombus and no concurrent
      deep vein thrombosis. Patients at high risk for recurrent venous thromboembolism
      or with deep vein thrombosis warrant anticoagulation. The provider is ultimately
      responsible for appropriate evaluation with risk stratification and selective
      testing. CONCLUSIONS: SSPE presents a quandary, because the literature differs in
      showing harm despite increased diagnosis. American College of Chest Physicians
      guidelines for the treatment of SSPE take into account the patient, the imaging,
      and other imaging modalities. Providers should use risk stratification with
      shared decision-making in the evaluation and treatment of SSPE.

PMID- 27720542
TI  - Metabolism of ibuprofen in higher plants: A model Arabidopsis thaliana cell
      suspension culture system.
AB  - The uptake and metabolism of ibuprofen (IBU) by plants at the cellular level was
      investigated using a suspension culture of A. thaliana. Almost all IBU added to
      the medium (200 MUM) was metabolized or bound to insoluble structures in 5 days.
      More than 300 metabolites were determined by liquid chromatography-high
      resolution mass spectrometry (LC-HRMS) analysis, and most of these are first
      reported for plants here. Although hydroxylated derivatives formed by oxidation
      on the isobutyl side chain were the main first-step products of IBU degradation,
      conjugates of these products with sugar, methyl and amino acid groups were the
      dominant metabolites in the culture. The main portion of total added IBU (81%)
      was accumulated in the extractable intracellular pool, whereas the cultivation
      medium fraction contained only 19%. The amount of the insoluble cell-wall-bound
      IBU was negligible (0.005% of total IBU).

PMID- 27720544
TI  - Phosphorus leakage from fisheries sector - A case study in Thailand.
AB  - Although phosphorus (P) is an essential element needed for all lives, excess P
      can be harmful to the environment. The objective of this study aims to determine
      P flows in the fisheries sector of Thailand consisting of both sea and freshwater
      activities of captures and cultures. Currently, the annual fisheries catch
      averages 3.44 +/- 0.50 Mt. Most comes from marine capture 1.95 +/- 0.46 Mt,
      followed by coastal aquaculture 0.78 +/- 0.09 Mt, freshwater aquaculture 0.49 +/-
      0.05 Mt, and inland capture 0.22 +/- 0.01 Mt. Of this total, about 11% is
      contained in fresh products directly sold in local markets for consumption, while
      89% is sent to processing factories prior to being sold in local markets and
      exported. The quantities of P entering the fisheries sector come from captures,
      import of fisheries products and feed produced from agriculture. This P input to
      the fisheries sector is found to average 28,506 t P.y-1 based on the past ten
      year records. Of this total, P input from captures accounts for 76%; while, 11%
      represents aquatic feeds from agriculture and animal manures. About 13% is
      obtained from the imports of fishery products. Coastal and freshwater
      aquacultures are found to be P consumers because their feeds are almost all
      produced from agricultural crops grown inland. Moreover, these activities cause
      most of P losses, approximately 10,188 t P.y-1, which account for 89% of the
      total P loss from the fisheries sector. Overall, P in the fisheries sector is
      found to mobilize through three channels: (a) 44% is consumed within the country;
      (b) about 16% is exported; and, (c) 40% is lost from the ecosystem. Based on the
      results of this work it is recommended that future research be directed on ways
      to minimize P loss and maximize P recycle in Thailand's fisheries sector as to
      enhance its food security and curtail water pollution.

PMID- 27720543
TI  - Colloidal properties and stability of aqueous suspensions of few-layer graphene:
      Importance of graphene concentration.
AB  - Understanding the colloidal stability of graphene is essential for predicting its
      transport and ecological risks in aquatic environments. We investigated the
      agglomeration of 14C-labeled few-layer graphene (FLG) at concentrations spanning
      nearly four orders of magnitude (2 MUg/L to 10 mg/L) using dynamic light
      scattering and sedimentation measurements. FLG agglomerates formed rapidly in
      deionized water at concentrations >3 mg/L. From 1 mg/L to 3 mg/L, salt-induced
      agglomeration was decreased with dilution of FLG suspensions; the critical
      coagulation concentration of the more concentrated suspension (3 mg/L) was
      significantly lower than the dilute suspension (1 mg/L) in the presence of NaCl
      (1.6 mmol/L and 10 mmol/L, respectively). In contrast, FLG underwent slow
      agglomeration and settling at concentrations <=0.1 mg/L in NaCl solutions and
      ambient waters with low ionic strength (<10 mmol/L). FLG nanoparticles with
      smaller lateral sizes (25 nm-75 nm) were shown to agglomerate more slowly than
      larger FLG, and these small FLG particles exhibited greater bioaccumulation in
      zebrafish embryo and stronger chorion penetration ability than larger FLG
      particles. These findings suggest that FLG at more environmentally relevant
      concentration is relatively stable and may have implications for exposure of
      small FLG to ecological receptors.

PMID- 27720545
TI  - Infectious bacterial pathogens, parasites and pathological correlations of sewage
      pollution as an important threat to farmed fishes in Egypt.
AB  - This paper is a part of a multi-disciplinary research "Application of
      Decentralized On-Site Water Treatment System in Egypt for Use in Agriculture and
      Producing Safe Fish and Animal Proteins". The project aimed to investigate the
      environmental impact of implementing sewage water before and after treatment
      using the effluent of the on-site decentralized Japanese' Johkasou system, in
      agriculture and producing fish protein. The aim is to establish such system in
      Egypt to strengthen the sanitary conditions of water resources. In the present
      study, the impact of the sewage pollution in some fish farms at El-Fayyum, Port
      Said and El-Dakahlia governorates in Egypt was carried out. Water and fish
      (Oreochromis niloticus and Mugil cephalus) samples were collected from private
      fish farms of such localities. Bacteriological and chemical examination of water
      samples revealed the existence of coliforms and many other bacterial species of
      significant human health hazards. The chemical parameters of water showed a
      marked deviation from normal levels while examination of fish flesh specimens
      indicated contamination with Streptococcus Sp., Staphylococcus Sp., and
      Salmonella in all examined localities. Other bacterial isolates of human health
      importance (Morganella morganii, Pseudomonas cepacia and Enterococcos durans)
      were identified. The parasitological examination revealed the presence of
      encysted metacercariae (EMC); Diplostomatidae, Prohemistomatidae and
      Heterphyidae. Moreover, two protozoan parasites (Mxyoboulus tilapiae and
      Ichthyophthirius multifilis) were also recorded. The histopathological
      examination revealed mild tissue reaction in case of bacterial infection and
      severe pathological lesions in different organs in case of EMC infection.
      Lamellar hyperplasia and mononuclear cell infiltration in branchial tissue was
      common findings. In skeletal muscles, atrophy of muscle fibres, myolysis and
      myophagia were detected.

PMID- 27720546
TI  - Biochar increases arsenic release from an anaerobic paddy soil due to enhanced
      microbial reduction of iron and arsenic.
AB  - Previous studies have shown that biochar enhances microbial reduction of iron
      (Fe) oxyhydroxide under anaerobic incubation. However, there is a lack of data on
      its influence on arsenic (As) release from As-contaminated paddy soils. In this
      study, paddy soil slurries (120 mg As kg-1) were incubated under anaerobic
      conditions for 60 days with and without the addition of biochar (3%, w/w)
      prepared from rice straw at 500  degrees C. Arsenic release, Fe reduction, and As
      fractionation were determined at 1, 10, 20, 30, and 60 d, while Illumina
      sequencing and real-time PCR were used to characterize changes in soil microbial
      community structure and As transformation function genes. During the first month
      of incubation, As released into soil solution increased sharply from 27.9 and
      55.9 to 486 and 630 MUg kg-1 in unamended and biochar amended slurries, with
      inorganic trivalent As (AsIII) being the dominant specie (52.7-91.0% of total
      As). Compared to unamended slurries, biochar addition increased As and ferrous
      ion (Fe2+) concentrations in soil solution but decreased soil As concentration in
      the amorphous Fe/Al oxide fraction (F3). Difference in released As between
      biochar and unamended treatments (DeltaAs) increased with incubation time,
      showing strong linear relationships (R2 = 0.23-0.33) with DeltaFe2+ and DeltaF3,
      confirming increased As release due to enhanced Fe reduction. Biochar addition
      increased the abundance of Fe reducing bacteria such as Clostridum (27.3% vs.
      22.7%), Bacillus (3.34% vs. 2.39%), and Caloramator (4.46% vs. 3.88%). In
      addition, copy numbers in biochar amended slurries of respiratory As reducing
      (arrA) and detoxifying reducing genes (arsC) increased 19.0 and 1.70 fold,
      suggesting microbial reduction of pentavalent As (AsV) adsorbed on Fe oxides to
      AsIII, further contributing to increased As release.

PMID- 27720547
TI  - Hyperspectral leaf reflectance of Carpinus betulus L. saplings for urban air
      quality estimation.
AB  - In urban areas, the demand for local assessment of air quality is high. The
      existing monitoring stations cannot fulfill the needs. This study assesses the
      potential of hyperspectral tree leaf reflectance for monitoring traffic related
      air pollution. Hereto, 29 Carpinus betulus saplings were exposed to an
      environment with either high or low traffic intensity. The local air quality was
      estimated by leaf saturation isothermal remanent magnetization (SIRM). The VIS
      NIR leaf reflectance spectrum (350-2500 nm) was measured using a handheld
      AgriSpec spectroradiometer (ASD Inc.). Secondary, leaf chlorophyll content index
      (CCI), specific leaf area (SLA) and water content (WC) were determined. To gain
      insight in the link between leaf reflectance and air quality, the correlation
      between SIRM and several spectral features was determined. The spectral features
      that were tested are plain reflectance values, derivative of reflectance, two
      band indices using the NDVI formula and PCA components. Spectral reflectance for
      wavelength bands in the red and short wave IR around the red edge, were
      correlated to SIRM with Pearson correlations of up to R = -0.85 (R2 = 0.72).
      Based on the spectral features and combinations thereof, binomial logistic
      regression models were trained to classify trees into high or low traffic
      pollution exposure, with classification accuracies up to 90%. It can be concluded
      that hyperspectral reflectance of C. betulus leaves can be used to detect
      different levels of air pollution within an urban environment.

PMID- 27720548
TI  - Synthesis, structure determination, and biological evaluation of phenylsulfonyl
      hydrazide derivatives as potential anti-inflammatory agents.
AB  - In our previous research, a novel series of phenylsulfonyl hydrazide derivatives
      were found to reduce LPS-induced PGE2 levels in RAW 264.7 macrophage cells via an
      inhibition of mPGES-1 enzyme. Recently, it was found that a regioisomeric mixture
      of phenylsulfonyl hydrazide was formed depending on the reaction conditions,
      which favor either of two regioisomers. One regioisomer corresponds to a kinetic
      product (7a-7c) and the other regioisomer corresponds to a thermodynamic product
      (8a-8c). Among them, the structure of kinetic product 7b was confirmed by
      measuring single X-ray crystallography. In vitro PGE2 assay studies showed that
      the kinetic product (7a and 7b; IC50=0.69 and 0.55MUM against PGE2) is generally
      more potent than the thermodynamic product (8a and 8b; IC50=>10 and 0.79MUM
      against PGE2). A molecular docking study also exhibited that the kinetic product
      (7a) has a higher MolDock Score (-147.4) than that of 8a (-142.4), which is
      consistent with the PGE2 assay results. A new potent phenylsulfonyl hydrazide
      (7d; IC50=0.06MUM against PGE2) without affecting COX-1 and COX-2 enzyme
      activities was identified based on these overall results.

PMID- 27720549
TI  - A monocyclic neodysiherbaine analog: Synthesis and evaluation.
AB  - Monocyclic analog of neuroexcitatory neodysiherbaine has been designed and
      stereoselectively synthesized in 0.40% yield over total 24 steps starting from d
      ribose, by employing domino aldol-Cannizzaro reaction and stereoselective aldol
      reaction for construction of two quaternary carbon stereogenic centers at C4 and
      C6 positions, respectively. The hyperactivity of neodysiherbaine in mice was
      found to deteriorate in the novel analog, upon intracerebroventricular injection.

PMID- 27720551
TI  - Associations with Retinal Pigment Epithelium Thickness Measures in a Large
      Cohort: Results from the UK Biobank.
AB  - PURPOSE: To describe associations of ocular and systemic factors with retinal
      pigment epithelium (RPE)-Bruch's membrane (BM) complex thickness as measured by
      spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Multisite
      community-based study. This research has been conducted using the UK Biobank
      Resource. PARTICIPANTS: Sixty-seven thousand three hundred eighteen people 40 to
      69 years old received questionnaires, physical examination, and eye examination,
      including macular SD OCT. Systematic selection process identified 34 652 eyes
      with high-quality SD OCT images from normal individuals for analysis. METHODS: We
      included people with no self-reported ocular disease, diabetes, or neurologic
      disorders; visual acuity of >=20/25; refraction between -6 diopters (D) to 6 D,
      and IOP of 6 to 21 mmHg. Only high-quality, well-centered SD OCT images with
      central, stable fixation were included. Descriptive statistics, t tests, and
      regression analyses were performed. Multivariate regression modeling was used to
      adjust for covariates and to identify relationships between RPE-BM thickness and
      ocular and systemic features. MAIN OUTCOME MEASURES: Retinal pigment epithelium
      BM thickness, as measured by SD OCT segmentation using Topcon Advanced Boundary
      Segmentation at 9 Early Treatment of Diabetic Retinopathy Study subfields.
      RESULTS: Mean RPE-BM thickness was 26.3 MUm (standard deviation, 4.8 MUm) at
      central subfield. Multivariate regression with age stratification showed that RPE
      thinning became apparent after age 45. Among those aged <=45, RPE-BM was
      significantly thicker among those of black or mixed/other race (+3.61 and +1.77
      MUm vs. white, respectively; P < 0.001) and higher hyperopia (+0.4 MUm/D; P <
      0.001), but not for other variables considered. Among those age >45, RPE-BM was
      significantly thinner with older age (-0.10 MUm/year; P < 0.001), Asian ethnicity
      (-0.45 MUm vs. white; P = 0.02), taller height (-0.02 MUm/cm; P < 0.001), higher
      IOP (-0.03 MUm/mmHg; P < 0.001), and regular smoking (-0.27 MUm vs. nonsmokers; P
      = 0.02). In contrast, RPE-BM was significantly thicker among black or mixed/other
      race (+3.29 MUm and +0.81 MUm vs. white, respectively; P < 0.001) and higher
      hyperopia (+0.28 MUm/D; P < 0.001). There was no significant association with sex
      or Chinese ethnicity. CONCLUSIONS: We describe novel findings of RPE-BM thickness
      in normal individuals, a structure that varies with age, ethnicity, refraction,
      IOP, and smoking. The significant association with IOP is especially interesting
      and may have relevance for the etiology of glaucoma, while the association
      between age and smoking may have relevance for the etiology of age-related
      macular degeneration.

PMID- 27720553
TI  - Illuminating the lifecourse of place in the longitudinal study of neighbourhoods
      and health.
AB  - Place and health are inextricably entwined. Whilst insights have been gained into
      the associations between places, such as neighbourhoods, and health, the
      understanding of these relationships remains only partial. One of the reasons for
      this relates to time and change and the inter-relationships between the dynamic
      nature of both neighbourhoods and health. This paper argues that the lifecourse
      of place can be used as a conceptual framework to understand the evolution and
      ongoing development of neighbourhoods, and their impact on the geographies of
      health, past, present and future. Moreover, this paper discusses the capacity of
      a longitudinal form of enquiry - latent transition analysis - that is able to
      operationalise conceptual models of the lifecourse of place. To date, latent
      transition analysis has not been applied to the study of neighbourhoods and
      health. Drawing on research across a range of disciplines including developmental
      psychology, sociology, geography and epidemiology, this paper also considers
      praxis-based implications and recommendations for applications of latent
      transition analysis that aim to advance understanding of how neighbourhoods
      affect health in and over time.

PMID- 27720554
TI  - Sharing qualitative data & analysis. With whom and how widely?: A response to
      'Promises and pitfalls of data sharing in qualitative research'.

PMID- 27720550
TI  - IGF-I in the clinics: Use in retinopathy of prematurity.
AB  - Retinopathy of prematurity is a potentially blinding disease, which is associated
      with low neonatal IGF-I serum concentrations and poor growth. In severe cases
      impaired retinal vessel growth is followed by pathologic neovascularization,
      which may lead to retinal detachment. IGF-I may promote growth even in catabolic
      states. Treating preterm infants with recombinant human (rh) IGF-I to
      concentrations normally found during gestation has been suggested to have a
      preventative effect on ROP. A recent phase 2 study treating infants (gestational
      age between 23weeks+0days and 27weeks +6days) with rhIGF-I/IGF binding protein-3
      until 30 postmenstrual weeks showed no effect on ROP but a 53% reduction in
      severe bronchopulmonary dysplasia and 44% reduction in severe intraventricular
      hemorrhage. Oxygen is a major risk factor for ROP and during the phase 2 study
      oxygen saturation targets were increased to 90-95%, due to national guidelines,
      which might have affected ROP rate and severity making increased IGF-I a weaker
      preventative factor for ROP.

PMID- 27720552
TI  - Aqueous Chlorhexidine for Intravitreal Injection Antisepsis: A Case Series and
      Review of the Literature.
AB  - PURPOSE: To determine the incidence of endophthalmitis in a large clinical series
      using aqueous chlorhexidine for antisepsis before intravitreal injection and to
      review the ophthalmic literature regarding chlorhexidine efficacy and safety.
      DESIGN: Multicenter retrospective case series. PARTICIPANTS: All patients
      receiving intravitreal injections from 7 retinal specialists. METHODS: An audit
      of intravitreal injections performed by retinal specialists who exclusively used
      aqueous chlorhexidine 0.05% or 0.1% for prophylaxis of infective endophthalmitis
      was undertaken. The incidence of endophthalmitis was determined from August 1,
      2011, to February 28, 2015. A literature review was performed to critically
      appraise the ocular safety and efficacy of aqueous chlorhexidine. MAIN OUTCOME
      MEASURES: Incidence of endophthalmitis after intravitreal injections. RESULTS: A
      total of 40 535 intravitreal injections were performed by 7 retinal specialists
      across 3 centers. Chlorhexidine was well tolerated, and only 1 patient with a
      suspected allergic reaction was noted. Three cases of endophthalmitis were
      identified with 1 culture-positive case. The 0.0074% (1 in 13 512) per-injection
      rate of endophthalmitis in this series compares favorably with previous series in
      which povidone-iodine has been used. CONCLUSIONS: Aqueous chlorhexidine was
      associated with a low rate of postinjection endophthalmitis and was well
      tolerated by patients.

PMID- 27720555
TI  - Structure-based design of ester compounds to inhibit MLL complex catalytic
      activity by targeting mixed lineage leukemia 1 (MLL1)-WDR5 interaction.
AB  - WDR5 is an essential protein for enzymatic activity of MLL1. Targeting the
      protein-protein interaction (PPI) between MLL1 and WDR5 represents a new
      potential therapeutic strategy for MLL leukemia. Based on the structure of
      reported inhibitor WDR5-0103, a class of ester compounds were designed and
      synthetized to disturb MLL1-WDR5 PPI. These inhibitors efficiently inhibited the
      histone methyltransferase activity in vitro. Especially, WL-15 was one of the
      most potent inhibitors, blocking the interaction of MLL1-WDR5 with IC50 value of
      26.4nM in competitive binding assay and inhibiting the catalytic activity of MLL1
      complex with IC50 value of 5.4MUM. Docking model indicated that ester compounds
      suitably occupied the central cavity of WDR5 protein and recapitulated the
      interactions of WDR5-0103 and the hydrophobic groups and key amino greatly
      increased the activity in blocking MLL1-WDR5 PPI.

PMID- 27720556
TI  - Insights into tyrosinase inhibition by compounds isolated from Greyia radlkoferi
      Szyszyl using biological activity, molecular docking and gene expression
      analysis.
AB  - Greyia radlkoferi ethanol extract and its five compounds were tested for their
      inhibitory activity against the mushroom tyrosinase enzyme and melanin production
      on melanocytes. The crude extract showed significant tyrosinase inhibition with
      IC50 of 17.96MUg/ml. This is the first report of the isolation of these 5
      compounds from Greyia radlkoferi. 2',4',6'-Trihydroxydihydrochalcone showed the
      highest tyrosinase inhibition at 17.70MUg/ml (68.48MUM), with low toxicity when
      compared with crude extract. This compound is therefore, a key component in the
      crude extract, which is responsible for tyrosinase inhibitory activity. The RT
      qPCR indicated that the mechanism of action is most likely post transcriptional.
      Further, the molecular docking study showed that tyrosinase inhibitory activity
      depends on interaction of the compound with Cu2+ ions at the active site. This is
      the first report of the tyrosinase inhibitory activity of the G. radlkoferi
      extract and molecular insights on interaction of its compounds with Cu2+ ions as
      the driving factor for tyrosinase inhibition. These results suggest that the
      extract of G. radlkoferi and the compound 2',4',6'-trihydroxydihydrochalcone have
      great potential to be further developed as pharmaceutical or cosmetic agents for
      use against dermatological disorders associated with melanin.

PMID- 27720557
TI  - Discovery, design and synthesis of 6H-anthra[1,9-cd]isoxazol-6-one scaffold as
      G9a inhibitor through a combination of shape-based virtual screening and
      structure-based molecular modification.
AB  - Protein lysine methyltransferase G9a is widely considered as an appealing
      antineoplastic target. Herein we present an integrated workflow combining shape
      based virtual screening and structure-based molecular modification for the
      identification of novel G9a inhibitors. The shape-based similarity screening
      through ROCS overlay on the basis of the structure of UNC0638 was performed to
      identify CPUY074001 contained a 6H-anthra[1,9-cd]isoxazol-6-one scaffold as a
      hit. Analysis of the binding mode of CPUY074001 with G9a and 3D-QSAR results, two
      series compounds were designed and synthesized. The derivatives were confirmed to
      be active by in vitro assay and the SAR was explored by docking stimulations.
      Besides, several analogues showed acceptable anti-proliferative effects against
      several cancer cell lines. Among them, CPUY074020 displayed potent dual G9a
      inhibitory activity and anti-proliferative activity. Furthermore, CPUY074020
      induced cell apoptosis in a dose-dependent manner and displayed a significant
      decrease in dimethylation of H3K9. Simultaneously, CPUY074020 showed reasonable
      in vivo PK properties. Altogether, our workflow supplied a high efficient
      strategy in the identification of novel G9a inhibitors. Compounds reported here
      can serve as promising leads for further study.

PMID- 27720558
TI  - Critical Review of Current Approaches for Echocardiographic Reproducibility and
      Reliability Assessment in Clinical Research.
AB  - BACKGROUND: There is no broadly accepted standard method for assessing the
      quality of echocardiographic measurements in clinical research reports, despite
      the recognized importance of this information in assessing the quality of study
      results. METHODS: Twenty unique clinical studies were identified reporting
      echocardiographic data quality for determinations of left ventricular (LV)
      volumes (n = 13), ejection fraction (n = 12), mass (n = 9), outflow tract
      diameter (n = 3), and mitral Doppler peak early velocity (n = 4). To better
      understand the range of possible estimates of data quality and to compare their
      utility, reported reproducibility measures were tabulated, and de novo estimates
      were then calculated for missing measures, including intraclass correlation
      coefficient (ICC), 95% limits of agreement, coefficient of variation (CV),
      coverage probability, and total deviation index, for each variable for each
      study. RESULTS: The studies varied in approaches to reproducibility testing,
      sample size, and metrics assessed and values reported. Reported metrics included
      mean difference and its SD (n = 7 studies), ICC (n = 5), CV (n = 4), and Bland
      Altman limits of agreement (n = 4). Once de novo estimates of all missing indices
      were determined, reasonable reproducibility targets for each were identified as
      those achieved by the majority of studies. These included, for LV end-diastolic
      volume, ICC > 0.95, CV < 7%, and coverage probability > 0.93 within 30 mL; for LV
      ejection fraction, ICC > 0.85, CV < 8%, and coverage probability > 0.85 within
      10%; and for LV mass, ICC > 0.85, CV < 10%, and coverage probability > 0.60
      within 20 g. CONCLUSIONS: Assessment of data quality in echocardiographic
      clinical research is infrequent, and methods vary substantially. A first step to
      standardizing echocardiographic quality reporting is to standardize assessments
      and reporting metrics. Potential benefits include clearer communication of data
      quality and the identification of achievable targets to benchmark quality
      improvement initiatives.

PMID- 27720559
TI  - Humeral head osteotomy in shoulder arthroplasty: a comparison between
      anterosuperior and inferoanterior resection techniques.
AB  - BACKGROUND: The best chance that a shoulder arthroplasty will restore motion and
      muscle balance across the glenohumeral joint is by closely replicating natural
      articular morphology. Defining the humeral osteotomy plane along clear landmarks
      at the anatomic neck is critical. We hypothesized that a new osteotomy, based on
      alternative landmarks on the anatomic neck, would restore 3-dimensional humeral
      head morphology more reliably than the traditional osteotomy. METHODS: The
      anatomic neck was digitized in 30 human cadaver shoulders and compared with its 3
      dimensional computed tomography reconstruction. Two different osteotomy
      techniques were virtually performed: the traditional, following the
      anterosuperior anatomic neck; and a new technique, defined by the inferoanterior
      anatomic neck. The length-width difference and orientation (retroversion,
      inclination) of the resection area were compared between the techniques and with
      native anatomy. RESULTS: Length-width difference of the anterosuperior resection
      area was higher than in the inferoanterior osteotomy (6 +/- 2 mm vs. 3 +/- 1 mm;
      P < .001). Retroversion of the anterosuperior resection plane was higher than the
      native head (50 degrees  +/- 12 degrees  vs. 37 degrees  +/- 11 degrees ; P <
      .001), whereas retroversion after the inferoanterior osteotomy (32 degrees  +/-
      12 degrees ) did not differ from native (P = .057). Inclination differed after
      the anterosuperior osteotomy (129 degrees  +/- 5 degrees ) and the inferoanterior
      osteotomy (127 degrees  +/- 4 degrees ) compared with the native head (134
      degrees  +/- 4 degrees ; P <= .001). CONCLUSION: The inferoanterior referenced
      osteotomy generated a more circular resection area, matching the native humeral
      head retroversion more closely than in the anterosuperior technique. This study
      suggests that in shoulder arthroplasty, the humeral resection level should be
      referenced at the inferoanterior rather than the anterosuperior anatomic neck.
      Further studies should investigate the biomechanical effects of this alternative
      resection plane.

PMID- 27720560
TI  - Glenoid deformity in the coronal plane correlates with humeral head changes in
      osteoarthritis: a radiographic analysis.
AB  - BACKGROUND: A variety of measurements can be used to assess radiographic
      osteoarthritic changes of the shoulder. This study aimed to analyze the
      correlation between the radiographic humeral-sided Samilson and Prieto
      classification system and 3 different radiographic classifications describing the
      changes of the glenoid in the coronal plane. METHODS: The study material included
      standardized radiographs of 50 patients with idiopathic osteoarthritis before
      anatomic shoulder replacement. On the basis of radiographic measurements, the
      cases were evaluated using the Samilson and Prieto grading system, angle beta,
      inclination type, and critical shoulder angle by 2 independent observers.
      RESULTS: Classification measurements showed an excellent agreement between
      observers. Our results showed that the humeral-sided Samilson and Prieto grading
      system had a statistically significant good correlation with angle beta (observer
      1, r = 0.74; observer 2, r = 0.77; P < .05) and a statistically significant
      excellent correlation with the inclination type of the glenoid (observer 1, r  =
      0.86; observer 2, r = 0.8; P < .05). A poor correlation to the critical shoulder
      angle was observed (r = -0.14, r = 0.03; P > .05). CONCLUSIONS: The grade of
      humeral-sided osteoarthritis according to Samilson and Prieto correlates with the
      glenoid-sided osteoarthritic changes of the glenoid in the coronal plane
      described by the angle beta and by the inclination type of the glenoid. Higher
      glenoid-sided inclination is associated with higher grade of osteoarthritis in
      primary shoulder osteoarthritis.

PMID- 27720561
TI  - Histiocytic proliferations.
AB  - The study of Histiocytic lesions has been a passion of Pepper Dehner over the
      years. He has contributed several case series and reviews on various categories
      of these diseases for over 4 decades, with his earliest articles in the 1970s. He
      has written on all aspects of the disease including seminal articles on
      Langerhans cell histiocytosis (LCH) and their prognostic features, his
      experiences with regressing atypical histiocytosis, his encounters with malignant
      histiocytosis, and classic articles on juvenile xanthogranuloma. His
      contributions in the form of chapters in his 2 editions of the unique Pediatric
      Pathology textbook are no less important than his many articles. His experience
      with these lesions is highlighted in the 2 editions of the book, and the author
      and the audience is left wishing for more in a more current version. This article
      is more of a journey from descriptions and understanding of these various
      histiocytic syndromes to the current understanding and classifications with
      molecular inputs and recent advances. This article is dedicated to a master
      Clinician, Pathologist, and mentor whose contributions to the field of Pediatric
      Pathology makes him deserve beyond all doubt the title of "Father of Modern
      Pediatric Pathology."

PMID- 27720562
TI  - Pediatric renal and genitourinary tract tumors and the contributions of Dr. Louis
      "Pepper" Dehner therewith.
AB  - Dr. Louis "Pepper" Dehner is an internationally renowned surgical pathologist,
      especially in the subspecialty of pediatric pathology. Although his clinical and
      academic expertise are broad, with over 400 published articles, some of his most
      intriguing contributions have been in the area of pediatric renal and
      genitourinary pathology. This review focuses on the entities in these following
      organ systems where he has focused his efforts: malignant rhabdoid tumor, renal
      medullary carcinoma, Ewing sarcoma/peripheral neuroectodermal tumor, and the
      DICER1-related lesions cystic nephroma, embryonal rhabdomyosarcoma of the uterine
      cervix, and Sertoli-Leydig cell tumor.

PMID- 27720563
TI  - Contributions of Dr. Louis "Pepper" Dehner to the art of cutaneous pathology, the
      first pediatric dermatopathologist.
AB  - Dr. Louis "Pepper" Dehner has been one of the most influential surgical
      pathologists of the last century. Authoring more than 450 publications, he is the
      premier modern pediatric pathologist. Perhaps, an area that he is less recognized
      and in which we would like to describe his contributions, is his role as a
      creator of the art of pediatric dermatopathology. Dr. Dehner has had at least 50
      major publications describing, discovering, and orienting the discipline in the
      fields of fibrohistiocytic disorders of childhood, vascular tumors, and
      histiocytosis among many others. Dr. Dehner has clearly manifested that while
      many similarities between adult and pediatric surgical pathology exist, "children
      get different diseases." It is because of his mindful analysis and translation of
      the clinico-pathologic and biologic correlative between specific entities and
      advances in the field he has made that we are honored to describe some of his
      contributions to this particular area.

PMID- 27720564
TI  - Correlation between lymph node count and survival and a reappraisal of lymph node
      ratio as a predictor of survival in gastric cancer: A multi-institutional cohort
      study.
AB  - PURPOSE: The purpose of this study is to evaluate the correlation between lymph
      node count (LNC) and survival and to evaluate whether lymph node ratio (LNR)
      which is related to LNC is a better predictor of survival for gastric cancer than
      the N category of UICC/AJCC through a multi-institutional cohort study. METHODS:
      The study cohort included 3284 patients from eight institutions. Lower and upper
      quartiles of LNC were used for comparisons. The cut-off values (0, 0.06, 0.27,
      and 0.49) for the LNR categories were based on Classification and Regression
      Trees techniques. Akaike information criteria (AIC) for Cox regression models was
      used to evaluate goodness of fit between competing predictor variables (LNR vs. N
      category). RESULTS: The 5-year disease-specific survival (DSS) rates of lower and
      upper quartiles of LNC were 82.2% and 84.8%. In the subgroup analysis of pN
      category, the upper quartile of LNC showed better survival than the lower
      quartile in pN2, pN3a, and pN3b subgroups. Regarding LNR, 5-year DSS of LNR 0, 0
      0.06, 0.06-0.27, 0.27-0.49, and >0.49 was 95.3%, 88.7%, 70.6%, 42.7%, and 17.2%
      respectively. Multivariate analysis showed that pT, pN, LNR, residual tumor
      status, distant metastasis, and tumor differentiation significantly affected
      survival. The analysis also confirmed superiority of LNR compared with N category
      in the AIC analysis. CONCLUSION: Higher LNC correlated with better survival in
      patients with pN2, pN3a, and pN3b gastric cancer. Our data indicate that LNR is a
      better predictor of survival than N category of UICC/AJCC.

PMID- 27720565
TI  - Comments on "intraoperative near-infrared fluorescence imaging using indocyanine
      green in colorectal carcinomatosis surgery: proof of concept".

PMID- 27720566
TI  - Analyses of pressure ulcer incidence in inpatient setting in a Portuguese
      hospital.
AB  - AIM: To gain more insight into the magnitude of the problem of pressure ulcer
      incidence in general wards of a Portuguese hospital. MATERIAL AND METHODS:
      Retrospective cohort analysis of electronic health record database from 7132
      adult patients admitted to medical and surgical wards of Aveiro Hospital during
      2012. The development of (at least) one pressure ulcer during the length of stay
      was associated with age, gender, type of admission, specialty units, first Braden
      Scale score, length of stay, patient discharge outcome and ICD-9 diagnosis.
      RESULTS: An incidence of 3.4% participants with pressure ulcer category I-IV in
      inpatient setting during 2012. During the length of stay, 320 new pressure ulcers
      were developed, most of them category/stage II. The sacrum/coccyx and the
      trochanters were the most problematic areas. CONCLUSIONS: The major risk factor
      for the development of a new pressure ulcer during the length of stay was the
      presence of (at least) one pressure ulcer at the first skin assessment. The
      length of stay itself, age and lower Braden Scale scores of our participants also
      played an important role in the odds of developing a pressure ulcer. Infectious
      diseases, traumatism and fractures and respiratory diseases were the ICD-9
      diagnoses with higher frequency of participants that developed (at least) one
      pressure ulcer during the length of stay. It's important to standardize
      procedures and documentation in all care settings. The documentation of nursing
      interventions is vital to evaluate the impact of evidence-based nursing.

PMID- 27720567
TI  - Bacterial meningitis without pleocytosis.

PMID- 27720568
TI  - The impact of push-dose phenylephrine use on subsequent preload expansion in the
      ED setting.
AB  - BACKGROUND: The utilization of bolus-dose phenylephrine (PHE) has transitioned to
      the emergency department (ED) for the treatment of acutely hypotensive patients,
      despite a paucity of literature in this setting. METHODS: This was a single
      center retrospective chart review of the utilization of bolus-dosed PHE for acute
      hypotension in the ED at an academic non-forprofit hospital. The primary
      objective of this study is to report the frequency of patients that were
      initiated on a continuous vasopressor infusion (CVI) within 30 minutes after the
      first administration of bolus-dose PHE. Secondary objectives included an
      observational description of the impact of early preload expansion (fluids) on
      the initiation of CVIs in the setting of bolus-dose PHE in the ED. RESULTS:
      Seventy-three patients met inclusion criteria for analysis. The primary outcome,
      46.5% (n = 34) of patients were initiated on a CVI within 30 minutes following
      bolus-dose PHE. Initial preload expansion (30 mL/kg of IV fluids) was found to be
      significantly disproportionate with 34.2% appropriately fluid challenged vs 65.8%
      (P = .0048). In addition, a significant decrease in the number of PHE bolus doses
      were required [1.5 vs 2.3 (P = .01)] in the adequately IVF challenged group. For
      secondary endpoints, PHE was most commonly indicated for peri-intubation
      hypotension (n = 52, 71.2%). Significant adverse events were documented for 15
      (20.5%) patients, with bradycardia (n = 7; 9.6%) as the most common adverse
      event. CONCLUSIONS: Initial preload IVF expansion was found to be significantly
      disproportionate, and appears to be associated with an increase number of
      phenylephrine bolus doses in our study population.

PMID- 27720569
TI  - Comments on "Proposal and validation of a new model to estimate survival for
      hepatocellular carcinoma patients".

PMID- 27720570
TI  - [Wolman disease].

PMID- 27720571
TI  - [A rare cause of adrenal calcifications].

PMID- 27720572
TI  - Stopping epilepsy treatment in seizure remission: Good or bad or both?
AB  - PURPOSE: To review the outcome of epilepsy after stopping antiepileptic drugs in
      remission. RESULTS: Stopping antiepileptic drugs (AEDs) in remission is routinely
      done in many patients. Although the consequences of an unexpected relapse seizure
      in the 2 years after stopping AEDs may cause anguish and social issues, the
      impact on the long term seizure outlook of the epilepsy is minimal, if any.
      Discontinuation of drug treatment does not seem to affect the long-term prognosis
      but exposes patients who were seizure-free for years to a transient two-fold risk
      of seizures for the first 2 years after stopping AEDs. In addition, 20% of
      patients who were seizure-free for years, do not become seizure-free immediately
      after restarting AED treatment after relapse. The list of potential pitfalls is
      long. Patients with juvenile myoclonic epilepsy, those with prior withdrawal
      attempts and late remission have a higher risk of relapse. CONCLUSION: Stopping
      AEDs in remission does not affect the long-term patterns of epilepsy and some
      patients report a better general health in a life without AEDs. High-risk
      patients should not be generally encouraged to stop their AEDs in remission. We
      need new drugs that combine anti-seizure and antiepileptogenic effects to prevent
      seizure relapse and flare up of epilepsy after stopping AEDs in remission.

PMID- 27720573
TI  - Endpoint Accuracy in Manual Control of a Steerable Needle.
AB  - PURPOSE: To study the ability of a human operator to manually correct for errors
      in the needle insertion path without partial withdrawal of the needle by means of
      an active, tip-articulated steerable needle. MATERIALS AND METHODS: The needle is
      composed of a 1.32-mm outer-diameter cannula, with a flexure joint near the tip,
      and a retractable stylet. The bending stiffness of the needle resembles that of a
      20-gauge hypodermic needle. The needle functionality was evaluated in manual
      insertions by steering to predefined targets and a lateral displacement of 20 mm
      from the straight insertion line. Steering tasks were conducted in 5 directions
      and 2 tissue simulants under image guidance from a camera. The repeatability in
      instrument actuations was assessed during 100 mm deep automated insertions with a
      linear motor. In addition to tip position, tip angles were tracked during the
      insertions. RESULTS: The targeting error (mean absolute error +/- standard
      deviation) during manual steering to 5 different targets in stiff tissue was 0.5
      mm +/- 1.1. This variability in manual tip placement (1.1 mm) was less than the
      variability among automated insertions (1.4 mm) in the same tissue type. An
      increased tissue stiffness resulted in an increased lateral tip displacement. The
      tip angle was directly controlled by the user interface, and remained unaffected
      by the tissue stiffness. CONCLUSIONS: This study demonstrates the ability to
      manually steer needles to predefined target locations under image guidance.

PMID- 27720574
TI  - Optimizing radiation exposure for CT localizer radiographs.
AB  - INTRODUCTION: The trend towards submillisievert CT scans leads to a higher dose
      fraction of localizer radiographs in CT examinations. The already existing
      technical capabilities make dose optimization of localizer radiographs
      worthwhile. Modern CT scanners apply automatic exposure control (AEC) based on
      attenuation data in such a localizer. Therefore not only this aspect but also the
      detectability of anatomical landmarks in the localizer for the desired CT scan
      range adjustment needs to be considered. MATERIALS AND METHODS: The effective
      dose of a head, chest, and abdomen-pelvis localizer radiograph with standard
      factory settings and user-optimized settings was determined using Monte Carlo
      simulations. CT examinations of an anthropomorphic phantom were performed using
      multiple sets of acquisition parameters for the localizer radiograph and the AEC
      for the subsequent helical CT scan. Anatomical landmarks were defined to assess
      the image quality of the localizer. CTDIvol and effective mAs per slice of the
      helical CT scan were recorded to examine the impact of localizer settings on a
      helical CT scan. RESULTS: The dose of the localizer radiograph could be decreased
      by more than 90% while the image quality remained sufficient when selecting the
      lowest available settings (80kVp, 20mA, pa tube position). The tube position
      during localizer acquisition had a greater impact on the AEC than the reduction
      of tube voltage and tube current. Except for the use of a pa tube position, all
      changes of acquisition parameters for the localizer resulted in a decreased total
      radiation exposure. CONCLUSION: A dose reduction of CT localizer radiograph is
      necessary and possible. In the examined CT system there was no negative impact on
      the modulated helical CT scan when the lowest tube voltage and tube current were
      used for the localizer.

PMID- 27720575
TI  - Transoral Stensen's Duct Approach: A 22-case retrospective study.
AB  - INTRODUCTION: Parotid gland duct lithiasis is preferentially managed using
      minimally-invasive techniques such as sialendoscopy and lithotripsy. However,
      these 2 techniques cannot remedy all obstructions and other techniques such as
      the Transoral Stensen's Duct Approach (TSDA) may sometimes be helpful. MATERIAL
      AND METHODS: A retrospective study of patients treated with TSDA was conducted to
      evaluate this procedure between 2006 and 2013. Criteria for inclusion were:
      failures for lithiases (22 patients and 28 lithiases) treated with sialendoscopy
      and/or lithotripsy for parotid gland duct obstruction. Mean follow-up was 47.4
      months. Pain intensity, swelling and occurrence of infectious episodes were
      evaluated immediately and after middle-term and long-term follow-up (up to 36
      months). RESULTS: The best results were obtained for anterior lithiasis, with an
      87.5% immediate success rate. Morbidity was low with 2 transient facial nerve
      upper buccal branch palsies and 2 post-operative stenoses. DISCUSSION: TSDA is an
      easy-to-perform and safe technique that can be recommended in cases of
      sialendoscopy or lithotripsy failure for anterior-third parotid duct lithiasis.
      Even if this technique has shown limitations for more posterior lithiases, or
      other causes of obstruction (stenosis, megaduct), it requires no specific
      material and may be useful. It may avoid an external combined approach or a
      parotidectomy.

PMID- 27720576
TI  - Concordance of immune checkpoints within tumor immune contexture and their
      prognostic significance in gastric cancer.
AB  - Checkpoint blockade therapy has emerged as a novel approach for cancer
      immunotherapy in several malignancies. However, patient prognosis and disease
      progression relevant to immune checkpoints in gastric tumor microenvironment are
      not defined. This study aims to investigate the expression and prognostic
      significance of immune checkpoints within gastric cancer. In the study, a cohort
      of 398 cancer tissues from stage I to IV gastric cancer patients were assessed
      for programmed cell death 1 ligand 1 (PD-L1) expression and tumor-infiltrating
      lymphocyte (TIL) infiltration using immunohistochemistry to ascertain their
      survival correlation. The data revealed that higher TIL density correlated with
      less risk of disease progression, and exhibited survival benefits in gastric
      cancer patients, and PD-L1 positivity showed a significant association with the
      presence of high TIL infiltration. Furthermore, real-time quantitative polymerase
      chain reaction was performed to detect expression of multiple immune checkpoints
      with the relation to clinical outcome in 139 samples randomly selected from the
      same cohort, and higher messenger RNA levels of most immune checkpoints were
      associated with favorable outcome, while consistently showing a positive
      correlation with interferon gamma levels. In situ hybridization was used to
      determine the localization of Epstein-Barr virus (EBV) in 97 specimens, and
      showed EBV-positive gastric cancer samples correlated with PD-L1 expression and
      increased TIL density. These results suggest that induction of immune checkpoint
      within gastric cancer patients reflects a high immune infiltration density,
      especially in those with EBV-associated gastric cancer, which may direct patient
      selection for checkpoint blockade therapy.

PMID- 27720577
TI  - Early use of chemotherapy in metastatic prostate cancer.
AB  - Since 2010, five new antineoplastic therapies have been FDA approved for the
      treatment of metastatic prostate cancer. With additional treatment options,
      questions arose about the optimal sequence of these agents. Until recently,
      chemotherapy has been deferred until later in the disease course in favor of next
      generation androgen deprivation therapy. Prior to the development of abiraterone
      acetate and enzalutamide, clinical trials were opened investigating the
      combination of chemotherapy with androgen deprivation therapy in patients with
      metastatic hormone-sensitive disease. With the development of new oral therapies
      used to treat castration-resistant disease, these trials were largely forgotten
      or felt to be obsolete. Recently, two trials have been reported showing an
      overall survival benefit of the early use of chemotherapy in patients with
      hormone-naive prostate cancer, changing the treatment paradigm for metastatic
      disease. Here we review the history of chemotherapy in treating prostate cancer
      and the emerging evidence favoring its use as first-line therapy against
      metastatic hormone-sensitive disease.

PMID- 27720579
TI  - Site-specific diel mercury emission fluxes in landfill: Combined effects of
      vegetation and meteorological factors.
AB  - Mercury emission fluxes (MEFs) under different surface coverage conditions in a
      landfill were investigated in this study. The results show similar diel patterns
      of Hg emission flux under different coverage conditions, with peak fluxes
      occurring at midday and decreasing during night. We examined the effects of
      environmental factors on MEFs, such as the physiological characteristics of
      vegetation and meteorological conditions. The results suggest that growth of
      vegetation in the daytime facilitates the release of Hg in the anaerobic unit,
      while in the semi-aerobic unit, where vegetation had been removed, the higher
      mercury content of the cover soil prompted the photo-reduction pathway to become
      the main path of mercury release and increased MEFs. MEFs are positively
      correlated with solar radiation and air temperature, but negatively correlated
      with relative humidity. The correlation coefficients for MEFs with different
      environmental parameters indicate that in the anaerobic unit, solar radiation was
      the main influence on MEFs in September, while air temperature became the main
      determining factor in December. These observations suggest that the effects of
      meteorological conditions on the mercury release mechanism varies depending on
      the vegetation and soil pathways.

PMID- 27720578
TI  - Panic attacks and panic disorder in the American Indian community.
AB  - Panic disorder is a common mental health condition, but little is known about
      panic disorder in non-Caucasian populations. The purpose of this study is to
      describe the epidemiology, clinical features, and comorbidities of panic attacks
      and panic disorder in two large American Indian (AI) tribes (N=3084). A
      culturally-adapted version of the Composite International Diagnostic Interview
      assessed panic attacks, panic disorder, and various psychiatric comorbidities.
      After adjusting for age, gender, and tribe, linear and logistic regression
      analyses were conducted to compare AIs with panic disorder to those with panic
      attacks only on clinical characteristics and panic symptoms. Approximately 8.5%
      (N=234) of American Indians reported a lifetime history of panic attacks. Among
      individuals with panic attacks, comorbid posttraumatic stress disorder was higher
      in females (p=0.03) and comorbid alcohol-related disorders were higher in males
      (p<=0.001). The prevalence and clinical features of panic attacks and panic
      disorder in American Indians were similar to epidemiologic studies with majority
      populations. However, in contrast to earlier research, panic symptoms were
      similar in both males and females, and different patterns of comorbidity emerged.
      Future research should examine the availability and accessibility of evidence
      based panic treatments for this traditionally underserved population.

PMID- 27720580
TI  - Modelling of composting process of different organic waste at pilot scale:
      Biodegradability and odor emissions.
AB  - The composting process of six different compostable substrates and one of these
      with the addition of bacterial inoculums carried out in a dynamic respirometer
      was evaluated. Despite the heterogeneity of the compostable substrates,
      cumulative oxygen demand (OD, mgO2kgVS) was fitted adequately to an exponential
      regression growing until reaching a maximum in all cases. According to the
      kinetic constant of the reaction (K) values obtained, the wastes that degraded
      more slowly were those containing lignocellulosic material (green wastes) or less
      biodegradable wastes (sewage sludge). The odor emissions generated during the
      composting processes were also fitted in all cases to a Gaussian regression with
      R2 values within the range 0.8-0.9. The model was validated representing real
      odor concentration near the maximum value against predicted odor concentration of
      each substrate, (R2=0.9314; 95% prediction interval). The variables of maximum
      odor concentration (ouE/m3) and the time (h) at which the maximum was reached
      were also evaluated statistically using ANOVA and a post-hoc Tukey test taking
      the substrate as a factor, which allowed homogeneous groups to be obtained
      according to one or both of these variables. The maximum oxygen consumption rate
      or organic matter degradation during composting was directly related to the
      maximum odor emission generation rate (R2=0.9024, 95% confidence interval) when
      only the organic wastes with a low content in lignocellulosic materials and no
      inoculated waste (HRIO) were considered. Finally, the composting of OFMSW would
      produce a higher odor impact than the other substrates if this process was
      carried out without odor control or open systems.

PMID- 27720581
TI  - Omalizumab for the treatment of chronic spontaneous urticaria in clinical
      practice.

PMID- 27720582
TI  - Lactobacillus reuteri DSM 17938 plus vitamin D3 as ancillary treatment in
      allergic children with asthma.

PMID- 27720583
TI  - Ovarian Cancer: An Evidence-Based, Easy-to-Use Prediction Rule to Optimize the
      Use of Follow-up Chest CT.
AB  - PURPOSE: To create and validate an evidence-based prediction rule to optimize use
      of follow-up chest CT for ovarian cancer. METHODS: In this Institutional Review
      Board-approved retrospective study performed at two academic medical centers,
      electronic medical records from January through December 2013 at center 1 (USA)
      and January 2012 through December 2013 at center 2 (South Korea) were searched to
      identify consecutive chest CTs performed within 5 years of initial cytoreductive
      surgery in patients with pathologically proven ovarian cancer. Three separate
      study cohorts were created: cohort 1, 316 CTs (in 150 patients) with high-grade
      serous ovarian cancer (HGSC) from center 1; cohort 2, 374 CTs (81 patients) with
      HGSC from center 2; and cohort 3, 87 CTs (56 patients) with non-HGSC histologies
      from center 1. A radiologist blinded to outcome of CT, using a prediction rule
      that utilized previously available information, categorized each CT into "high
      risk" (stage 4 at presentation and/or preexisting abdominal disease [disease
      below diaphragmatic dome, visualized on abdominal CT]) or "low-risk" (neither of
      above). A blinded radiologist then reviewed chest CTs in random order to record
      thoracic metastases above the diaphragmatic dome, and outcome was compared with
      prediction rule risk category. RESULTS: Among the three cohorts and in the total
      population, the prediction rule identified 94 of 316 (30%), 170 of 374 (45%), 53
      of 87 (61%), and 317 of 777 (41%) CTs as "low-risk," respectively. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      positive likelihood ratio, and negative likelihood ratio were as follows: cohort
      1: 95%, 35%, 24%, 97%, 1.46, 0.14; cohort 2: 88%, 53%, 29%, 95%, 1.87, 0.22;
      cohort 3: 88%, 66%, 21%, 98%, 2.59, 0.18; total population: 91%, 47%, 26%, 96%,
      1.72, 0.19. False-negative rate in the three cohorts and in total population was
      3 of 94 (3%), 8 of 170 (5%), 1 of 53 (2%), and 12 of 317 (4%); however, in each
      of these cases there was concurrent new abdominal disease. CONCLUSIONS: The easy
      to-use prediction rule helps avoid unnecessary chest CTs in patients with ovarian
      cancer with high sensitivity and negative predictive value, and with minimal risk
      of missing thoracoabdominal metastases.

PMID- 27720584
TI  - Growing up in wartime: Evidence from the era of two world wars.
AB  - We document the association between war-related shocks in childhood and adult
      outcomes for Europeans born during the first half of the twentieth century. Using
      a variety of data, at both the macro- and the micro-level, we address the
      following questions: What are the patterns of mortality among Europeans born
      during this period? Do war-related shocks in childhood and adolescence help
      predict adult health, human capital and wellbeing of the survivors? Are there
      differences by sex, socio-economic status in childhood, and age when the shocks
      occurred? At the macro-level, we show that the secular trend towards lower
      mortality was interrupted by dramatic increases in mortality during World War I,
      the Spanish Flu, the Spanish Civil War, and World War II, and we quantify the
      size of these mortality shocks. Different patterns characterize these high
      mortality episodes, with substantial variation by country, sex and age group. At
      the micro-level, we show that war-related hardship in childhood or adolescence,
      in particular exposure to war events and experience of hunger, is associated with
      worse physical and mental health, education, cognitive ability and subjective
      wellbeing at older ages. The strength of the association differs by sex and type
      of hardship, with war exposure being more important for females and experience of
      hunger for males. We also show that hardships matter more if experienced in
      childhood, and have stronger consequences if they last longer.

PMID- 27720585
TI  - Updated feasibility and reproducibility results of multi-institutional study of
      noninvasive breast tumor bed boost.
AB  - PURPOSE: To report updated feasibility and reproducibility results for high-dose
      rate noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole
      breast radiation therapy (WBRT) in the setting of expanded patient and treatment
      facility number. METHODS AND MATERIALS: Fifteen independent community-based and
      academic centers reported 518 early-stage breast cancer patients from July 2007
      to February 2015 on a privacy-encrypted online data registry. All patients'
      treatment included lumpectomy followed by combination of WBRT and NIBB. NIBB was
      completed with commercially available (AccuBoost, Billerica, MA) mammography
      based system using high-dose-rate 192Ir emissions along orthogonal axes. Harvard
      scale was used to grade cosmesis. RESULTS: Total patient cohort had median
      followup of 12 months (1-75 months) with subset of 268 having available cosmesis.
      Greater than 2- and 3-year followup was 29% and 14%, respectively. Entire cohort
      had 97.4% excellent/good (E/G) breast cosmesis and freedom from recurrence of
      97.6% at the final followup. WBRT timing with respect to NIBB delivery
      demonstrated no statistically significant difference in E/G cosmesis. Achieved
      E/G cosmesis rate was also not statistically significant (chi2p-value = 0.86)
      between academic and community institutions with 97.8% vs. 96.6%. CONCLUSIONS:
      NIBB represents an alternative method for delivery of breast tumor cavity boost
      that has shown feasibility in a diverse group of both academic and community
      based practices with reproducible early cosmesis and tumor control results.
      Recommendations are updated noting ideal timing of boost delivery likely to be
      before or early during WBRT given equal cosmesis and less documented treatment
      discomfort.

PMID- 27720587
TI  - Composition of growth factors and cytokines in lysates obtained from fresh versus
      stored pathogen-inactivated platelet units.
AB  - BACKGROUND: Platelet lysate is a readily available source of growth factors, and
      other mediators, which has been used in a variety of clinical applications.
      However, the product remains poorly standardized and the present investigation
      evaluates the composition of platelet lysate obtained from either fresh or stored
      pathogen-inactivated platelet units. MATERIALS AND METHODS: Platelet pooled units
      (n = 10) were obtained from healthy blood donors and tested according to standard
      procedures. All units were pathogen inactivated using amotosalen hydrochloride
      and UVA exposure. Platelet lysate was subsequently produced at two separate time
      points, either from fresh platelet units or after 5 days of storage, by repeated
      freeze-thaw cycles. The following mediators were determined at each time-point:
      EGF, FGF-2, VEGF, IGF-1, PDGF-AB/BB, BMP-2, PF4, TGF-beta isoform 1, IL-1beta, IL
      2, IL-6, IL-10, IL-12p70, 1L-17A, TNF-alpha, and IFN-gamma. RESULTS: The
      concentration of growth factors and cytokines was affected by time in storage.
      Notably, TGF-beta, PDGF-AB/BB, and PF4 showed an increase of 27.2% (p < 0.0001),
      29.5% (p = 0.04) and 8.2% (p = 0.0004), respectively. A decrease was seen in the
      levels of IGF-1 and FGF-2 with 22% (p = 0.041) and 11% (p = 0.01), respectively.
      Cytokines were present only in very low concentrations and all other growth
      factors remained stable with time in storage. CONCLUSION: The composition of
      mediators in platelet lysate obtained from pathogen-inactivated platelet units
      differs when produced from fresh and stored platelet units, respectively. This
      underscores the need for further standardization and optimization of this
      important product, which potentially may influence the clinical effects.

PMID- 27720586
TI  - Endoplasmic Reticulum Proteostasis Influences the Oligomeric State of an
      Amyloidogenic Protein Secreted from Mammalian Cells.
AB  - Transthyretin (TTR) is a tetrameric serum protein associated with multiple
      systemic amyloid diseases. In these disorders, TTR aggregates in extracellular
      environments through a mechanism involving rate-limiting dissociation of the
      tetramer to monomers, which then misfold and aggregate into soluble oligomers and
      amyloid fibrils that induce toxicity in distal tissues. Using an assay
      established herein, we show that highly destabilized, aggregation-prone TTR
      variants are secreted as both native tetramers and non-native conformations that
      accumulate as high-molecular-weight oligomers. Pharmacologic chaperones that
      promote endoplasmic reticulum (ER) proteostasis of destabilized TTR variants
      increase their fraction secreted as a tetramer and reduce extracellular aggregate
      populations. In contrast, disrupting ER proteostasis reduces the fraction of
      destabilized TTR secreted as a tetramer and increases extracellular aggregates.
      These results identify ER proteostasis as a factor that can affect conformational
      integrity and thus toxic aggregation of secreted amyloidogenic proteins
      associated with the pathology of protein aggregation diseases.

PMID- 27720588
TI  - A Highly Conserved Yet Flexible Linker Is Part of a Polymorphic Protein-Binding
      Domain in Myosin-Binding Protein C.
AB  - The nuclear magnetic resonance (NMR) structure of the tri-helix bundle (THB) of
      the m-domain plus C2 (DeltamC2) of myosin-binding protein C (MyBP-C) has revealed
      a highly flexible seven-residue linker between the structured THB and C2.
      Bioinformatics shows significant patterns of conservation across the THB-linker
      sequence, with the linker containing a strictly conserved serine in all MyBP-C
      isoforms. Clinically linked mutations further support the functional significance
      of the THB-linker region. NMR, small-angle X-ray scattering, and binding studies
      show the THB-linker plus the first ten residues of C2 undergo dramatic changes
      when DeltamC2 binds Ca2+-calmodulin, with the linker and C2 N-terminal residues
      contributing significantly to the affinity. Modeling of all available
      experimental data indicates that the THB tertiary structure must be disrupted to
      form the complex. These results are discussed in the context of the THB-linker
      and the N-terminal residues of C2 forming a polymorphic binding domain that could
      accommodate multiple binding partners in the dynamic sarcomere.

PMID- 27720590
TI  - Sono-crystallization kinetics of K2SO4: Estimation of nucleation, growth,
      breakage and agglomeration kinetics.
AB  - Application of ultrasound in crystallization has showed improved process
      characteristics. Although several attempts have been made in the past to study
      the sono-crystallization kinetics, only nucleation and crystal growth were
      considered, neglecting breakage and agglomeration of crystals. In this study, an
      attempt is made for the estimation of the kinetic parameters of all the phenomena
      occurring simultaneously during sono-crystallization. For this, both conventional
      and ultrasonic crystallization of K2SO4-water system has been reported. Sono
      crystallization experiments were carried out using ultrasonic horn operating at
      20 kHz frequency. Reduction in the induction time, reduction in metastable zone
      width (MSZW), narrowing of crystal size distribution (CSD) were the key
      observations of sono-crystallization experiments. Population balance equations
      (PBE) were used to model the crystallization system and the various kinetic
      parameters have been estimated. The kinetic parameters obtained for conventional
      crystallization and sonocrystallization were compared. The estimated parameters
      suggest an increase in nucleation and breakage rate during sono-crystallization.
      Growth rates were observed to be of the same order of magnitude for both
      conventional and sonocrystallization. While agglomeration during sono
      crystallization was found to be negligible.

PMID- 27720589
TI  - Crystal Structure of the Neuropilin-1 MAM Domain: Completing the Neuropilin-1
      Ectodomain Picture.
AB  - Neuropilins (NRPs) are single-pass transmembrane receptors involved in several
      signaling pathways that regulate key physiological processes such as vascular
      morphogenesis and axon guidance. The MAM domain of NRP, which has previously been
      implicated in receptor multimerization, was the only portion of the ectopic
      domain of the NRPs for which the structure, until now, has been elusive. Using
      site-directed mutagenesis in the linker region preceding the MAM domain we
      generated a protein construct amenable to crystallization. Here we present the
      crystal structure of the MAM domain of human NRP1 at 2.24 A resolution. The
      protein exhibits a jellyroll topology, with Ca2+ ions bound at the inter-strand
      space enhancing the thermostability of the domain. We show that the MAM domain of
      NRP1 is monomeric in solution and insufficient to drive receptor dimerization,
      which leads us to propose a different role for this domain in the context of NRP
      membrane assembly and signaling.

PMID- 27720592
TI  - Sonochemical synthesis and structural determination of novel the nano-card house
      Cu(II) metal-organic coordination system.
AB  - A sonochemical method by using various time and concentrations of initial
      reagents and power of irradiation, was used to synthesize nano-card house of a
      new copper(II) metal-organic coordination system, {[Cu2(p-2yeinh)2Cl2].(H2O)}n
      (1), where p-2yeinh=pyridin-2-yl ethylidene-isonicotinohydrazide. The compound
      was characterized by scanning electron microscopy (SEM), elemental analysis, IR
      spectroscopy, X-ray powder diffraction (XPRD), and single crystal X-ray analysis.
      The X-ray structure revealed that the Cu(II) atom is coordinated by one oxygen
      and three nitrogen atoms from two p-2yeinh ligands and one chloride anion with a
      CuN3OCl donor set with square pyramid geometry. This arrangement produces a large
      quadric nuclear square ring composed of four square pyramid Cu(II) moieties
      linked together by two p-2yeinh units (M4L4). The adjacent frameworks connected
      by strong hydrogen bonding interactions of methanol molecules that interact
      together and with the rings and pi-pi interactions of adjacent aromatic rings of
      p-2yeinh and other weak interactions. Consequently, the labile interactions also
      allow the discrete structure to form a 3D metal-organic coordination network. CuO
      nanoparticles were obtained by thermolysis of 1 at 180 degrees C with oleic acid
      as a surfactant. The average diameter of the nanoparticles was estimated by XPRD
      to be 38nm. The morphology and size of the prepared CuO nanoparticles were
      further studied using SEM.

PMID- 27720591
TI  - Ultrasound-assisted CO2 flooding to improve oil recovery.
AB  - CO2 flooding process as a common enhanced oil recovery method may suffer from
      interface instability due to fingering and gravity override, therefore, in this
      study a method to improve the performance of CO2 flooding through an integrated
      ultraosund-CO2 flooding process is presented. Ultrasonic waves can deliver energy
      from a generator to oil and affect its properties such as internal energy and
      viscosity. Thus, a series of CO2 flooding experiments in the presence of
      ultrasonic waves were performed for controlled and uncontrolled temperature
      conditions. Results indicate that oil recovery was improved by using ultrasound
      assisted CO2 flooding compared to conventional CO2 flooding. However, the changes
      were more pronounced for uncontrolled temperature conditions of ultrasound
      assisted CO2 flooding. It was found that ultrasonic waves create a more stable
      interface between displacing and displaced fluids that could be due to the
      reductions in viscosity, capillary pressure and interfacial tension. In addition,
      higher CO2 injection rates, increases the recovery factor in all the experiments
      which highlights the importance of injection rate as another factor on reduction
      of the fingering effects and improvement of the sweep efficiency.

PMID- 27720593
TI  - Sonocatalytic degradation of ciprofloxacin using synthesized TiO2 nanoparticles
      on montmorillonite.
AB  - TiO2/Montmorillonite (TiO2/MMT) nanocomposite as sonocatalyst was produced by
      immobilizing synthesized TiO2 on the surface of montmorillonite. The
      characteristics of produced nanocomposite were investigated using XRD, XRF, FTIR,
      TEM, SEM, EDX, UV-vis DRS and nitrogen adsorption-desorption analyses. The
      synthesized TiO2 and TiO2/MMT samples were applied as catalysts for sonocatalytic
      degradation of ciprofloxacin (CIP). The performance of the TiO2/MMT was greater
      than pure TiO2 sample in treatment of CIP solution. The degradation efficiency of
      the CIP by sonocatalytic process was affected by solution pH, catalyst dosage,
      initial CIP concentrations and ultrasonic power. Degradation efficiency of 65.01%
      was obtained at the pH of 6, catalyst dosage of 0.2gL-1, initial CIP
      concentration of 10mgL-1 and ultrasonic power of 650WL-1. It was observed that
      the presence of inorganic and organic scavengers suppressed the performance of
      sonocatalytic process. The stability of the nanocomposite was studied in several
      successive experiments, and the degradation efficiency declined only 61.48% after
      4 repeated experiments. The main degradation by-products were recognized by GC-MS
      method to propose the possible sonocatalytic mechanism for the degradation of
      CIP.

PMID- 27720594
TI  - Photoelectrocatalytic degradation of oxalic acid using WO3 and stratified
      WO3/TiO2 photocatalysts under sunlight illumination.
AB  - The WO3 and stratified WO3/TiO2 thin films are successfully prepared by the spray
      pyrolysis method. The structural, morphological, compositional and
      photoelectrocatalytic properties of WO3 and stratified WO3/TiO2 thin films are
      studied. XRD analysis confirms that films are polycrystalline with monoclinic and
      tetragonal crystal structures for WO3 and TiO2 respectively. The SEM images
      clearly show 3D sheeted porous structure of the as-prepared TiO2 forms on WO3 in
      stratified WO3/TiO2 samples. The synthesized photoelectrodes was used as catalyst
      for photoelectrocatalytic degradation of oxalic acid in aqueous medium. The rate
      constant (k) was evaluated as a function of the initial concentration of species.
      A significant decrease in concentrations of organic species was observed from COD
      analysis. The photoelectrocatalytic degradation effect is relatively higher in
      the case of the stratified WO3/TiO2 than WO3 thin film photoelectrode in the
      degradation of oxalic acid and 83% removal efficiency of oxalic acid is obtained
      after 180min. Based on the obtained experimental data, the possible
      photoelectrocatalytic reaction mechanism was proposed. The photoelectrocatalytic
      experimental results indicate that stratified WO3/TiO2 photoelectrode is the
      promising material for removing of water pollutants.

PMID- 27720595
TI  - Drug therapy problems and medication discrepancies during care transitions in
      super-utilizers.
AB  - OBJECTIVES: First, to investigate the prevalence and types of drug therapy
      problems and medication discrepancies among super-utilizers, and associated
      patient characteristics. Second, to examine the outcomes of pharmacist
      recommendations and estimated cost avoidance through care transitions support
      focused on medication management. DESIGN: Retrospective analysis of the
      pharmacist-led interventions as part of the SafeMed Program. SETTING: A large
      nonprofit health care system serving the major medically underserved areas in
      Memphis, Tennessee. PARTICIPANTS: Three hundred seventy-four super-utilizing
      SafeMed participants with multiple chronic conditions and polypharmacy.
      INTERVENTION: Comprehensive medication review, medication therapy management,
      enhanced discharge planning, home visits, telephone follow-up, postdischarge
      medication reconciliation, and care coordination with physicians. MAIN OUTCOME
      MEASURES: Types of drug therapy problems, outcomes of pharmacist recommendations,
      estimated cost avoided, medication discrepancies, and self-reported medication
      adherence. RESULTS: Prevalence of drug therapy problems and postdischarge
      medication discrepancies was 80.7% and 75.4%, respectively. The most frequently
      occurring drug therapy problems were enrollee not receiving needed medications
      (33.4%), underuse of medications (16.9%), and insufficient dose or duration
      (11.2%). Overall 50.8% of the pharmacist recommendations were accepted by
      physicians and patients, resulting in an estimated cost avoidance of $293.30 per
      drug therapy problem identified. Multivariate analysis indicated that
      participants with a higher number of comorbidities were more likely to have
      medication discrepancies (odds ratio 1.23 [95% CI 1.05-1.44]). Additional
      contributors to postdischarge medication discrepancies were difficulty picking up
      and paying for medications and not being given necessary prescriptions before
      discharge. CONCLUSION: Drug therapy problems and medication discrepancies are
      common in super-utilizers with multiple chronic conditions and polypharmacy
      during transitions of care, and greater levels of comorbidity magnify risk.
      Pharmacist-led interventions in the SafeMed Program have demonstrated success in
      resolving enrollees' medication-related issues, resulting in substantial
      estimated cost savings. Preliminary evidence suggests that the SafeMed model's
      focus on medication management has great potential to improve outcomes while
      reducing costs for vulnerable super-utilizing populations nationwide.

PMID- 27720596
TI  - Enhanced bio-catalytic performance and dye degradation potential of chitosan
      encapsulated horseradish peroxidase in a packed bed reactor system.
AB  - In this study, horseradish peroxidase (HRP) was immobilized onto chitosan beads
      by entrapment method and employed for the degradation of textile dyes. Stable and
      firm quality chitosan beads developed with 2.5% chitosan concentration exhibited
      maximum immobilization yield (~92.54+/-2.53%). The pH optimum of chitosan
      immobilized HRP (CTS-HRP) was marginally displaced towards alkaline region
      (pH7.5) than that of F-HRP which displayed its optimum activity at pH7.0. The
      free HRP (F-HRP) and CTS-HRP enzyme presented their maximum catalytic activities
      at 30 degrees C and 70 degrees C, respectively. Relative activities of F-HRP and
      CTS-HRP were decreased following pre-incubation above 30 degrees C and 50 degrees
      C, respectively and after 120min at 70 degrees C, the F-HRP, and CTS-HRP retained
      19.3+/-1.3 and 48.3+/-2.4% activities, accordingly. The CTS-HRP exhibited
      remarkably better resistance towards heavy metal induced activity inhibition. The
      effect of potential inhibitors on the activity of F-HRP and CTS-HRP was
      investigated and found that CTS-HRP was significantly less vulnerable to the
      denaturation caused by urea, ethylenediaminetetraacetic acid (EDTA), cysteine, 1,
      4-dithiothreitol and Triton X-100. Moreover, the CTS-assisted entrapped-HRP was
      also employed for the decolorization of four different textile dyes i.e. Remazol
      Brilliant Blue R (RBBR), Reactive Black 5 (RB5), Congo Red (CR) and Crystal
      Violet (CV). The CTS-HRP showed considerable decolorization efficacy in six
      consecutive batch operations. Results suggest that CTS-HRP is an attractive
      choice for use as industrial biocatalyst in larger scale bioremediation of
      textile dyes and effluents.

PMID- 27720597
TI  - Global warming increases the interspecific competitiveness of the invasive plant
      alligator weed, Alternanthera philoxeroides.
AB  - Global warming could accelerate the spread of invasive species to higher
      latitudes and intensify their effects on native species. Here, we report results
      of two years of field surveys along a latitudinal gradient (21 degrees N to 31
      degrees N) in southern China, to determine the species structure of the invasive
      plant Alternanthera philoxeroides community. We also performed a replacement
      series experiment (mono and mixed) to evaluate the effects of elevated
      temperature on the competitiveness of A. philoxeroides with the native co
      occurring species Digitaria sanguinalis. In the field survey, we found that the
      dominance of A. philoxeroides increased with increasing of latitude gradient
      while cover of D. sanguinalis decreased. In monospecific plantings, artificial
      warming reduced the length of D. sanguinalis roots. In mixed plantings, warming
      reduced both A. philoxeroides abundance and D. sanguinalis stem length when A.
      philoxeroides was more prevalent in the planting. Warming also significantly
      reduced D. sanguinalis biomass, but increased that of A. philoxeroides. In
      addition, elevated temperatures significantly reduced the relative yield (RY) of
      D. sanguinalis, particularly when A. philoxeroides was planted in higher
      proportion in the plot. These results suggest that the invasiveness of A.
      philoxeroides increased with increasing latitude, and that warming may increase
      the effectiveness of its interspecific competition with D. sanguinalis. Hence,
      under global warming conditions, the harm to native species from A. philoxeroides
      would increase at higher latitudes. Our findings are critical for predicting the
      invasiveness of alien species under climate change.

PMID- 27720598
TI  - Giant reed growth and effects on soil biological fertility in assisted
      phytoremediation of an industrial polluted soil.
AB  - Phytoremediation is a cost-effective "green technology" that uses plants to
      improve the soil properties of polluted sites, preventing the dispersion of
      pollutants and reducing the mobility of potentially toxic elements (PTEs) through
      their adsorption and accumulation by roots or precipitation within the root zone.
      Being highly tolerant to pollutants and other abiotic stresses, giant reed
      (Arundo donax L.) is a suitable biomass crop for phytoremediation of contaminated
      soils. We report the results of a two-year open-air lysimeter study aimed at
      assessing the adaptability of giant reed to grow on industrial substrates
      polluted by Pb and Zn and at testing commercial humic acids from leonardite as
      improvers of plant performance. We evaluated giant reed potential for: 1) biomass
      production for energy or biomaterial recovery; 2) PTE phytoextraction and 3) soil
      fertility restoration. Chemical fertility was monitored by measuring soil C while
      soil biological fertility was estimated by quantifying the abundance of bacterial
      functional genes regulating nitrogen fixation (nifH) and nitrification (amoA).
      Giant reed above-ground growth on the polluted soils was slightly lower (-16%)
      than on a non-polluted soil, with a preferential storage of biomass in the
      rhizome acting as a survival strategy in limiting growing conditions. Humic acids
      improved plant stress tolerance and production levels. As aerial biomass (shoots)
      did not accumulate PTEs, the plant in question can be used for bioenergy or
      biopolymer production. In contrast, below-ground biomass (rhizomes) accumulated
      PTEs, and can thus be harvested and removed from soil to improve phytoremediation
      protocols and also used as industrial biofuel. Giant reed growth increased the
      abundance of N-cycling bacteria and soil C in the rhizospheric soil, as well as
      reduced soil Pb and Zn EDTA extractable fraction.

PMID- 27720599
TI  - Persistence in the longitudinal distribution of lotic insects in a changing
      climate: a tale of two rivers.
AB  - The longitudinal distribution of many taxa in rivers is influenced by
      temperature. Here we took advantage of two older datasets on net-spinning
      caddisflies (Hydropsychidae) from contrasting European rivers to assess changes
      in species occurrence and relative abundance along the river by resampling the
      same sites, postulating that an increase in river temperature over the
      intervening period should have resulted in cool-adapted species retreating into
      the headwaters and warm adapted species expanding upstream. Distributional
      changes in the Welsh Usk were slight between 1968/69 and 2010, one rare species
      appearing at a single headwater site and one warm-adapted species disappearing
      from the main river. Distributional changes in the French Loire, between 1989-93
      and 2005, were similarly modest, with no consistent movement of species up- or
      downstream. We estimate that the decadal rate of increase in the mean summer
      daily maximum in the Usk was only 0.1 degrees C at one 'summer cool' headwater
      site, while a neighbouring 'summer warm' tributary increased by 0.16 degrees C
      per decade, and the main river by 0.22 degrees C. The Loire is warmer than the
      Usk and the mean decadal rates of increase, over the period 1989-2005, at three
      sites along the lower reaches were 0.39, 0.48 and 0.77 degrees C. Increases in
      stream and river temperature, therefore, were spatially variable and were not
      associated with consistent upstream movement of species in either of these (very
      different) rivers. We conclude that either the temperature increases have
      hitherto been insufficient to affect species distribution or, more speculatively,
      that it may not be possible for river organisms (that do not respond only to
      temperature) to move upstream because of a developing spatial mismatch between
      key habitat characteristics, some of them changing with the climate but others
      not.

PMID- 27720600
TI  - Relationship Between Energy Drink Consumption and Nutrition Knowledge in Student
      Athletes.
AB  - OBJECTIVE: To identify the relationships between energy drink consumption,
      nutrition knowledge, and socio-demographic characteristics in a convenience
      sample of student-athletes. DESIGN: Cross-sectional. SETTING: Online survey.
      PARTICIPANTS: A total of 194 student-athletes (112 female and 82 male). MAIN
      OUTCOME MEASURES: Socio-demographic characteristics, knowledge of human
      nutrition, energy drink consumption habits. ANALYSIS: Chi-square tests of
      independence, independent t tests, and hierarchical regression analyses were
      applied. RESULTS: Most student-athletes in the sample (85.5%) did not consume
      energy drinks, but those who did tended to be male (P = .004), had lower overall
      knowledge of nutrition (P = .02), and had a lower grade point average (P < .001)
      than did nonusers. Also, energy drink consumption was associated with the overall
      nutrition knowledge score when adjusted for socio-demographic characteristics,
      with nonusers having greater nutrition knowledge (P = .007) than users.
      CONCLUSIONS AND IMPLICATIONS: Student-athletes tend to refrain from energy drink
      use but those who use it have a tendency to have lower nutrition knowledge than
      do nonusers. Therefore, nutrition education targeted toward student-athletes
      should encompass the consumption of energy drinks because limited evidence shows
      the benefits of collegiate athletes consuming energy drinks.

PMID- 27720601
TI  - Low Nutrient Intake and Frailty Among Overweight and Obese Migrant Women From
      Ethnically Diverse Backgrounds Ages 60 Years and Older: A Mixed-Methods Study.
AB  - OBJECTIVE: To examine associations between energy/nutrient intakes and frailty in
      older migrant women, and to explore perceptions of body weight, dietary intake,
      and physical function. DESIGN: Cross-sectional, mixed-methods study. SETTING:
      Birmingham, United Kingdom. PARTICIPANTS: Seventy-six first-generation migrant
      women >= 60 years of age. MAIN OUTCOME MEASURES: Energy/nutrient intakes
      (assessed by 24-hour dietary recall), frailty (using the frailty phenotype), and
      links between perceptions of body weight, dietary intake, and physical function
      (via semi-structured interviews). ANALYSIS: Bivariate and logistic regression
      analyses examined associations between frailty and low energy/nutrient intakes.
      Interviews were analyzed using inductive thematic analysis. RESULTS: Seventy-six
      women completed a 24-hour dietary recall; 46 participated in a semi-structured
      interview. Low energy intake was associated with frailty (odds ratio [OR], 11.71;
      95% confidence interval [CI], 2.36-57.97). After adjusting for energy and other
      confounders, a low intake of > 3 nutrients was associated with frailty (OR, 6.58;
      95% CI, 1.01-43.08). Qualitative data suggest that dietary intake was influenced
      by concerns about body weight and perceptions that unhealthy foods reduce
      mobility. CONCLUSIONS AND IMPLICATIONS: Among older migrant women with high
      prevalence of overweight/obesity, an inadequate dietary intake may be a stronger
      predictor of frailty than weight loss. Dietary interventions should focus on
      healthy weight maintenance and optimization of nutritional adequacy and physical
      function.

PMID- 27720602
TI  - Evaluating the efficacy of epinastine ophthalmic solution using a conjunctivitis
      allergen challenge model in patients with birch pollen allergic conjunctivitis.
AB  - BACKGROUND: The efficacy of epinastine 0.05% ophthalmic solution for pollen
      allergic conjunctivitis has already been shown in a conjunctival allergen
      challenge (CAC) test using cedar pollen as a challenge. The present study
      investigated the efficacy of this solution against birch pollen conjunctivitis in
      a CAC test. METHODS: Ten adult subjects (eight males and two females) with
      asymptomatic birch pollen conjunctivitis were enrolled in this study. The average
      age of the subjects was 41.1 years. This study was conducted during a period
      without birch pollen dispersion. In each subject, the epinastine 0.05% ophthalmic
      solution was instilled in one eye, and an artificial tear fluid was instilled in
      the fellow eye in a double-blind manner. Five minutes or 4 h after the drug
      instillation, both eyes were challenged with an optimal concentration of birch
      pollen, and ocular itching and conjunctival hyperemia were then graded. Tears
      were collected before the drug instillation and 20 min after the pollen
      challenge, and the histamine level was measured. RESULTS: The ocular itching
      scores and palpebral conjunctival hyperemia scores of the epinastine-treated eyes
      were significantly lower than those of the contralateral control eyes when the
      eyes were pretreated with the drug 4 h before the CAC. There was a significant
      correlation between the tear histamine level and mean ocular itching score of
      three time points (3, 5 and 10 min) following the CAC in the control eyes but not
      the epinastine-treated eyes. CONCLUSIONS: Epinastine is effective in suppressing
      ocular itching and conjunctival hyperemia in birch pollen conjunctivitis.

PMID- 27720603
TI  - DSM-IV and DSM-5 Prevalence of Social Anxiety Disorder in a Population Sample of
      Older People.
AB  - OBJECTIVES: To examine the prevalence of social anxiety disorders (SAD) with (DSM
      IV) and without (DSM-5) the person's own assessment that the fear was
      unreasonable, in a population sample of older adults. Further, to determine
      whether clinical and sociodemographic correlates of SAD differ depending on the
      criteria applied. DESIGN: Cross-sectional. SETTING: General population in
      Gothenburg, Sweden. PARTICIPANTS: A random population-based sample of 75- and 85
      year olds (N = 1200) without dementia. MEASUREMENTS: Psychiatric research nurses
      carried out a semi-structured psychiatric examination including the Comprehensive
      Psychopathological Rating Scale. DSM-IV SAD was diagnosed with the Mini
      International Neuropsychiatric Interview. SAD was diagnosed according to DSM-IV
      and DSM-5 criteria. The 6-month duration criterion in DSM-5 was not applied
      because of lack of information. Other assessments included the Global Assessment
      of Functioning (GAF), the Brief Scale for Anxiety (BSA), and the Montgomery
      Asberg Depression Rating Scale (MADRS). RESULTS: The 1-month prevalence of SAD
      was 2.5% (N = 30) when the unreasonable fear criterion was defined in accordance
      with DSM-IV and 5.1% (N = 61) when the DSM-5 criterion was applied. Clinical
      correlates (GAF, MADRS, and BSA) were worse in SAD cases identified by either
      procedure compared with all others, and ratings for those reporting unreasonable
      fear suggested greater (albeit nonsignificant) overall psychopathology.
      CONCLUSIONS: Shifting the judgment of how reasonable the fear was, from the
      individual to the clinician, doubled the prevalence of SAD. This indicates that
      the DSM-5 version might increase prevalence rates of SAD in the general
      population. Further studies strictly applying all DSM-5 criteria are needed in
      order to confirm these findings.

PMID- 27720604
TI  - The electro/Fe3+/peroxydisulfate (PDS) process coupled to activated sludge
      culture for the degradation of tetracycline.
AB  - The removal of tetracycline (TC) by electro/Fe3+/peroxydisulfate process combined
      to the biological treatment is reported in this study. Effect of current density,
      peroxydisulfate (PDS) concentration, Fe3+ ions concentration and initial
      tetracycline concentration were investigated. The results indicated that the
      removal efficiency of TC increased with increasing current density and decreases
      with tetracycline initial concentration. This effect is attributed to the
      competition of TC and electrogenerated intermediate compounds for the consumption
      of oxidizing SO4- radicals. The TC degradation efficiency was improved
      significantly when the PDS and Fe3+ concentrations increased from 1 to 10 mM and
      1-2 mM, respectively. Above 10 mM PDS and 2 mM Fe3+ concentrations, a decrease of
      TC degradation efficiency was observed. The optimal operating conditions were: 2
      mM Fe3+, 0.06 mM TC, 10 mM PDS concentrations and 40 mA cm-2 current density.
      Under these conditions a total degradation of TC within only 40 min of reaction
      time and 98% of mineralization yield after 3 h electrolysis were obtained. The
      biodegradability of the solution after electro/Fe3+/peroxydisulfate pre-treatment
      showed that BOD5/COD ratio increased from 0.00 initially to 0.42, 0.46 and 0.83
      after 4 h, 5 h and 6 h, respectively, namely above the limit of biodegradability
      (0.4). The enhancement of biodegradability initially from 0.00 to 0.42 and 0.46
      after 4 h and 5 h of electrolysis respectively, was confirmed by the biological
      treatment, since 77.51% and 92.54% of the dissolved organic carbon was removed
      respectively by coupling Electro/Fe3 +/PDS pre-treatment and a biological
      treatment.

PMID- 27720605
TI  - A fuzzy-logic based decision-making approach for identification of groundwater
      quality based on groundwater quality indices.
AB  - Due to inherent uncertainties in measurement and analysis, groundwater quality
      assessment is a difficult task. Artificial intelligence techniques, specifically
      fuzzy inference systems, have proven useful in evaluating groundwater quality in
      uncertain and complex hydrogeological systems. In the present study, a Mamdani
      fuzzy-logic-based decision-making approach was developed to assess groundwater
      quality based on relevant indices. In an effort to develop a set of new hybrid
      fuzzy indices for groundwater quality assessment, a Mamdani fuzzy inference model
      was developed with widely-accepted groundwater quality indices: the Groundwater
      Quality Index (GQI), the Water Quality Index (WQI), and the Ground Water Quality
      Index (GWQI). In an effort to present generalized hybrid fuzzy indices a
      significant effort was made to employ well-known groundwater quality index
      acceptability ranges as fuzzy model output ranges rather than employing expert
      knowledge in the fuzzification of output parameters. The proposed approach was
      evaluated for its ability to assess the drinking water quality of 49 samples
      collected seasonally from groundwater resources in Iran's Sarab Plain during 2013
      2014. Input membership functions were defined as "desirable", "acceptable" and
      "unacceptable" based on expert knowledge and the standard and permissible limits
      prescribed by the World Health Organization. Output data were categorized into
      multiple categories based on the GQI (5 categories), WQI (5 categories), and GWQI
      (3 categories). Given the potential of fuzzy models to minimize uncertainties,
      hybrid fuzzy-based indices produce significantly more accurate assessments of
      groundwater quality than traditional indices. The developed models' accuracy was
      assessed and a comparison of the performance indices demonstrated the Fuzzy
      Groundwater Quality Index model to be more accurate than both the Fuzzy Water
      Quality Index and Fuzzy Ground Water Quality Index models. This suggests that the
      new hybrid fuzzy indices developed in this research are reliable and flexible
      when used in groundwater quality assessment for drinking purposes.

PMID- 27720606
TI  - Influence of high temperature on the performance of aerobic granular sludge in
      biological treatment of wastewater.
AB  - The effect of temperature on the efficiency of organics and nutrients removal
      during the cultivation of aerobic granular sludge (AGS) in biological treatment
      of synthetic wastewater was studied. With this aim, three 3 L sequencing batch
      reactors (SBRs) with influent loading rate of 1.6 COD g (L d)-1 were operated at
      different high temperatures (30, 40 and 50  degrees C) for simultaneous COD,
      phosphate and ammonia removal at a complete cycle time of 3 h. The systems were
      successfully started up and progressed to steady state at different cultivation
      periods. The statistical comparison of COD, phosphate and ammonia for effluent
      from the three SBRs revealed that there was a significant difference between
      groups of all the working temperatures of the bioreactors. The AGS cultivated at
      different high temperatures also positively correlated with the accumulation of
      elements including carbon, oxygen, phosphorus, silicon, iron, aluminium, calcium
      and magnesium that played important roles in the granulation process.

PMID- 27720607
TI  - The Germ Cell Fate of Cynomolgus Monkeys Is Specified in the Nascent Amnion.
AB  - The germ cell lineage ensures reproduction and heredity. The mechanism for germ
      cell specification in primates, including humans, has remained unknown. In
      primates, upon implantation the pluripotent epiblast segregates the amnion, an
      extra-embryonic membrane eventually ensheathing an embryo, and thereafter
      initiates gastrulation to generate three germ layers. Here, we show that in
      cynomolgus monkeys, the SOX17/TFAP2C/BLIMP1-positive primordial germ cells
      (cyPGCs) originate from the dorsal amnion at embryonic day 11 (E11) prior to
      gastrulation. cyPGCs appear to migrate down the amnion and, through proliferation
      and recruitment from the posterior amnion, expand in number around the posterior
      yolk sac by E17. Remarkably, the amnion itself expresses BMP4 and WNT3A,
      cytokines potentially critical for cyPGC specification, and responds primarily to
      them. Moreover, human PGC-like cells in vitro exhibit a transcriptome similar to
      cyPGCs just after specification. Our study identifies the origin of PGCs and a
      unique function of the nascent amnion in primates.

PMID- 27720609
TI  - A C. elegans Thermosensory Circuit Regulates Longevity through crh-1/CREB
      Dependent flp-6 Neuropeptide Signaling.
AB  - Sensory perception, including thermosensation, shapes longevity in diverse
      organisms, but longevity-modulating signals from the sensory neurons are largely
      obscure. Here we show that CRH-1/CREB activation by CMK-1/CaMKI in the AFD
      thermosensory neuron is a key mechanism that maintains lifespan at warm
      temperatures in C. elegans. In response to temperature rise and crh-1 activation,
      the AFD neurons produce and secrete the FMRFamide neuropeptide FLP-6. Both CRH-1
      and FLP-6 are necessary and sufficient for longevity at warm temperatures. Our
      data suggest that FLP-6 targets the AIY interneurons and engages DAF-9 sterol
      hormone signaling. Moreover, we show that FLP-6 signaling downregulates ins
      7/insulin-like peptide and several insulin pathway genes, whose activity
      compromises lifespan. Our work illustrates how temperature experience is
      integrated by the thermosensory circuit to generate neuropeptide signals that
      remodel insulin and sterol hormone signaling and reveals a neuronal-endocrine
      circuit driven by thermosensation to promote temperature-specific longevity.

PMID- 27720608
TI  - Acetylation of VGLL4 Regulates Hippo-YAP Signaling and Postnatal Cardiac Growth.
AB  - Binding of the transcriptional co-activator YAP with the transcription factor
      TEAD stimulates growth of the heart and other organs. YAP overexpression potently
      stimulates fetal cardiomyocyte (CM) proliferation, but YAP's mitogenic potency
      declines postnatally. While investigating factors that limit YAP's postnatal
      mitogenic activity, we found that the CM-enriched TEAD1 binding protein VGLL4
      inhibits CM proliferation by inhibiting TEAD1-YAP interaction and by targeting
      TEAD1 for degradation. Importantly, VGLL4 acetylation at lysine 225 negatively
      regulated its binding to TEAD1. This developmentally regulated acetylation event
      critically governs postnatal heart growth, since overexpression of an acetylation
      refractory VGLL4 mutant enhanced TEAD1 degradation, limited neonatal CM
      proliferation, and caused CM necrosis. Our study defines an acetylation-mediated,
      VGLL4-dependent switch that regulates TEAD stability and YAP-TEAD activity. These
      insights may improve targeted modulation of TEAD-YAP activity in applications
      from cardiac regeneration to cancer.

PMID- 27720610
TI  - Tbx2 and Tbx3 Act Downstream of Shh to Maintain Canonical Wnt Signaling during
      Branching Morphogenesis of the Murine Lung.
AB  - Numerous signals drive the proliferative expansion of the distal endoderm and the
      underlying mesenchyme during lung branching morphogenesis, but little is known
      about how these signals are integrated. Here, we show by analysis of conditional
      double mutants that the two T-box transcription factor genes Tbx2 and Tbx3 act
      together in the lung mesenchyme to maintain branching morphogenesis. Expression
      of both genes depends on epithelially derived Shh signaling, with additional
      modulation by Bmp, Wnt, and Tgfbeta signaling. Genetic rescue experiments reveal
      that Tbx2 and Tbx3 function downstream of Shh to maintain pro-proliferative
      mesenchymal Wnt signaling, in part by direct repression of the Wnt antagonists
      Frzb and Shisa3. In combination with our previous finding that Tbx2 and Tbx3
      repress the cell-cycle inhibitors Cdkn1a and Cdkn1b, we conclude that Tbx2 and
      Tbx3 maintain proliferation of the lung mesenchyme by way of at least two
      molecular mechanisms: regulating cell-cycle regulation and integrating the
      activity of multiple signaling pathways.

PMID- 27720611
TI  - Cellular Allometry of Mitochondrial Functionality Establishes the Optimal Cell
      Size.
AB  - Eukaryotic cells attempt to maintain an optimal size, resulting in size
      homeostasis. While cellular content scales isometrically with cell size,
      allometric laws indicate that metabolism per mass unit should decline with
      increasing size. Here we use elutriation and single-cell flow cytometry to
      analyze mitochondrial scaling with cell size. While mitochondrial content
      increases linearly, mitochondrial membrane potential and oxidative
      phosphorylation are highest at intermediate cell sizes. Thus, mitochondrial
      content and functional scaling are uncoupled. The nonlinearity of mitochondrial
      functionality is cell size, not cell cycle, dependent, and it results in an
      optimal cell size whereby cellular fitness and proliferative capacity are
      maximized. While optimal cell size is controlled by growth factor signaling, its
      establishment and maintenance requires mitochondrial dynamics, which can be
      controlled by the mevalonate pathway. Thus, optimization of cellular fitness and
      functionality through mitochondria can explain the requirement for size control,
      as well as provide means for its maintenance.

PMID- 27720613
TI  - An open-label randomized controlled clinical trial for comparison of continuous
      phenylephrine versus norepinephrine infusion in prevention of spinal hypotension
      during cesarean delivery.
AB  - BACKGROUND: During spinal anesthesia for cesarean delivery phenylephrine is the
      vasopressor of choice but can cause bradycardia. Norepinephrine has both beta-
      and alpha-adrenergic activity suitable for maintaining blood pressure with less
      bradycardia. We hypothesized that norepinephrine would be superior to
      phenylephrine, requiring fewer rescue bolus interventions to maintain blood
      pressure. METHODS: Eighty-five parturients having spinal anesthesia for elective
      cesarean delivery were randomized to Group P (phenylephrine 0.1MUg/kg/min) or
      Group N (norepinephrine 0.05MUg/kg/min) fixed-rate infusions. Rescue bolus
      interventions of phenylephrine 100MUg for hypotension, or ephedrine 5mg for
      bradycardia with hypotension, were given as required to maintain systolic blood
      pressure. Maternal hemodynamic variables were measured non-invasively. RESULTS:
      There was no difference between groups in the proportion of patients who required
      rescue vasopressor boluses (Group P: 65.8% [n=25] vs. Group N: 48.8% [n=21],
      P=0.12). The proportion of patients who received ?1 bolus of phenylephrine was
      similar between groups (Group P: 52.6% [n=20] vs. Group N: 46.5% [n=20], P=0.58).
      However, more patients received ?1 bolus of ephedrine in the phenylephrine group
      (Group P: 23.7% [n=9] vs. Group N: 2.3% [n=1], P<0.01). The incidence of emesis
      was greater in the phenylephrine group (Group P: 26.3% vs. Group P: 16.3%,
      P<0.001). Hemodynamic parameters including heart rate, the incidence of
      bradycardia, blood pressure, cardiac output, cardiac index, stroke volume, and
      systemic vascular resistance and neonatal outcome were similar between groups
      (all P<0.05). CONCLUSION: Norepinephrine fixed-rate infusion has efficacy for
      preventing hypotension and can be considered as an alternative to phenylephrine.

PMID- 27720614
TI  - Stimulation of contractions in pregnant human myometrium is associated with 5-HT3
      receptors.
AB  - BACKGROUND: Serotonin (5-HT) is known to play an important role in regulating
      uterine contractions. However, the specific receptors involved have not been well
      characterized. We evaluated whether 5-HT3 receptors exist in human myometrium,
      and their effects on myometrial contractility when stimulated by a 5-HT3 agonist.
      METHODS: Four tissue samples taken from patients undergoing hysterectomy (n=2)
      and elective cesarean delivery (n=2) were used to detect expression of 5-HT3
      receptors on the myometrium using western blotting. For isometric tension
      measurement, another 12 myometrial strips obtained from patients undergoing
      elective cesarean delivery were randomly divided into a control group (Group CON)
      and an RS56812 group (Group RG). In increasing doses from 10-7M to 10-4M,
      RS56812, a 5-HT3 receptor agonist, was used to investigate the contractile
      effects after bonding to the 5-HT3 receptor, following which the effects of
      granisetron were assessed. Amplitude, interval and duration of myometrial
      contractions were recorded. RESULTS: Proteins with a molecular mass of 55kDa,
      consistent with 5-HT3 receptors, were detected both on non-pregnant and late
      pregnant human uteri. RS56812 increased the contractile amplitude at
      concentrations of 10-6M, 10-5M and 10-4M, achieving maximum effect at 10-5M. A
      prolonged contractile interval was detected at the concentration of 10-4M.
      However, RS56812 showed no significant effect on contraction duration.
      Granisetron did not reverse the contractile effects induced by RS56812.
      CONCLUSION: 5-HT3 receptors are expressed on non-pregnant and pregnant uteri.
      RS56812 enhanced myometrial contractions, but this was not affected by
      granisetron, the mechanism of which requires further investigation.

PMID- 27720615
TI  - Opioids should be given before cord clamping for caesarean delivery under general
      anaesthesia.

PMID- 27720612
TI  - Adaptation to Stressors by Systemic Protein Amyloidogenesis.
AB  - The amyloid state of protein organization is typically associated with
      debilitating human neuropathies and is seldom observed in physiology. Here, we
      uncover a systemic program that leverages the amyloidogenic propensity of
      proteins to regulate cell adaptation to stressors. On stimulus, cells assemble
      the amyloid bodies (A-bodies), nuclear foci containing heterogeneous proteins
      with amyloid-like biophysical properties. A discrete peptidic sequence, termed
      the amyloid-converting motif (ACM), is capable of targeting proteins to the A
      bodies by interacting with ribosomal intergenic noncoding RNA (rIGSRNA). The
      pathological beta-amyloid peptide, involved in Alzheimer's disease, displays ACM
      like activity and undergoes stimuli-mediated amyloidogenesis in vivo. Upon signal
      termination, elements of the heat-shock chaperone pathway disaggregate the A
      bodies. Physiological amyloidogenesis enables cells to store large quantities of
      proteins and enter a dormant state in response to stressors. We suggest that
      cells have evolved a post-translational pathway that rapidly and reversibly
      converts native-fold proteins to an amyloid-like solid phase.

PMID- 27720616
TI  - Vertebral spread of epidural boluses with different pump flow rates in a porcine
      model.

PMID- 27720617
TI  - Ceropegia sandersonii Mimics Attacked Honeybees to Attract Kleptoparasitic Flies
      for Pollination.
AB  - Four to six percent of plants, distributed over different angiosperm families,
      entice pollinators by deception [1]. In these systems, chemical mimicry is often
      used as an efficient way to exploit the olfactory preferences of animals for the
      purpose of attracting them as pollinators [2,3]. Here, we report a very specific
      type of chemical mimicry of a food source. Ceropegia sandersonii (Apocynaceae), a
      deceptive South African plant with pitfall flowers, mimics attacked honeybees. We
      identified kleptoparasitic Desmometopa flies (Milichiidae) as the main
      pollinators of C. sandersonii. These flies are well known to feed on honeybees
      that are eaten by spiders, which we thus predicted as the model chemically
      mimicked by the plant. Indeed, we found that the floral scent of C. sandersonii
      is comparable to volatiles released from honeybees when under simulated attack.
      Moreover, many of these shared compounds elicited physiological responses in
      antennae of pollinating Desmometopa flies. A mixture of four compounds-geraniol,
      2-heptanone, 2-nonanol, and (E)-2-octen-1-yl acetate-was highly attractive to the
      flies. We conclude that C. sandersonii is specialized on kleptoparasitic fly
      pollinators by deploying volatiles linked to the flies' food source, i.e.,
      attacked and/or freshly killed honeybees. The blend of compounds emitted by C.
      sandersonii is unusual among flowering plants and lures kleptoparasitic flies
      into the trap flowers. This study describes a new example of how a plant can
      achieve pollination through chemical mimicry of the food sources of adult
      carnivorous animals.

PMID- 27720618
TI  - Stomatal Function Requires Pectin De-methyl-esterification of the Guard Cell
      Wall.
AB  - Stomatal opening and closure depends on changes in turgor pressure acting within
      guard cells to alter cell shape [1]. The extent of these shape changes is limited
      by the mechanical properties of the cells, which will be largely dependent on the
      structure of the cell walls. Although it has long been observed that guard cells
      are anisotropic due to differential thickening and the orientation of cellulose
      microfibrils [2], our understanding of the composition of the cell wall that
      allows them to undergo repeated swelling and deflation remains surprisingly poor.
      Here, we show that the walls of guard cells are rich in un-esterified pectins. We
      identify a pectin methylesterase gene, PME6, which is highly expressed in guard
      cells and required for stomatal function. pme6-1 mutant guard cells have walls
      enriched in methyl-esterified pectin and show a decreased dynamic range in
      response to triggers of stomatal opening/closure, including elevated osmoticum,
      suggesting that abrogation of stomatal function reflects a mechanical change in
      the guard cell wall. Altered stomatal function leads to increased conductance and
      evaporative cooling, as well as decreased plant growth. The growth defect of the
      pme6-1 mutant is rescued by maintaining the plants in elevated CO2,
      substantiating gas exchange analyses, indicating that the mutant stomata can
      bestow an improved assimilation rate. Restoration of PME6 rescues guard cell wall
      pectin methyl-esterification status, stomatal function, and plant growth. Our
      results establish a link between gene expression in guard cells and their cell
      wall properties, with a corresponding effect on stomatal function and plant
      physiology.

PMID- 27720620
TI  - Awakening of a Dormant Cyanobacterium from Nitrogen Chlorosis Reveals a
      Genetically Determined Program.
AB  - The molecular and physiological mechanisms involved in the transition of
      microbial cells from a resting state to the active vegetative state are
      critically relevant for solving problems in fields ranging from microbial ecology
      to infection microbiology. Cyanobacteria that cannot fix nitrogen are able to
      survive prolonged periods of nitrogen starvation as chlorotic cells in a dormant
      state. When provided with a usable nitrogen source, these cells re-green within
      48 hr and return to vegetative growth. Here we investigated the resuscitation of
      chlorotic Synechocystis sp. PCC 6803 cells at the physiological and molecular
      levels with the aim of understanding the awakening process of a dormant
      bacterium. Almost immediately upon nitrate addition, the cells initiated a highly
      organized resuscitation program. In the first phase, they suppressed any residual
      photosynthetic activity and activated respiration to gain energy from glycogen
      catabolism. Concomitantly, they restored the entire translational apparatus, ATP
      synthesis, and nitrate assimilation. After only 12-16 hr, the cells re-activated
      the synthesis of the photosynthetic apparatus and prepared for metabolic re
      wiring toward photosynthesis. When the cells reached full photosynthetic capacity
      after ~48 hr, they resumed cell division and entered the vegetative cell cycle.
      An analysis of the transcriptional dynamics during the resuscitation process
      revealed a perfect match to the observed physiological processes, and it
      suggested that non-coding RNAs play a major regulatory role during the lifestyle
      switch in awakening cells. This genetically encoded program ensures rapid
      colonization of habitats in which nitrogen starvation imposes a recurring growth
      limitation.

PMID- 27720619
TI  - A Surveillance System Ensures Crossover Formation in C. elegans.
AB  - Crossover (CO) recombination creates a physical connection between homologs that
      promotes their proper segregation at meiosis I (MI). Failure to realize an
      obligate CO causes homologs to attach independently to the MI spindle and
      separate randomly, leading to nondisjunction. However, mechanisms that determine
      whether homolog pairs have received crossovers remain mysterious. Here we
      describe a surveillance system in C. elegans that monitors recombination
      intermediates and couples their formation to meiotic progression. Recombination
      intermediates are required to activate the system, which then delays further
      processing if crossover precursors are lacking on even one chromosome. The
      synaptonemal complex, a specialized, proteinaceous structure connecting
      homologous chromosomes, is stabilized in cis on chromosomes that receive a
      crossover and is destabilized on those lacking crossovers, a process that is
      dependent on the function of the polo-like kinase PLK-2. These results reveal a
      new layer of communication between crossover-committed intermediates and the
      synaptonemal complex that functions as a cis-acting, obligate, crossover-counting
      mechanism.

PMID- 27720621
TI  - Males Can Benefit from Sexual Cannibalism Facilitated by Self-Sacrifice.
AB  - In a number of species, males are cannibalized by females after mating (reviewed
      in [1, 2]), and some males actually appear to facilitate their own cannibalism
      (reviewed in [3]). Such self-sacrifice can evolve if being eaten sufficiently
      enhances either fertilization success (mating effort) or offspring number or
      fitness (paternal effort). While there is some support for the mating-effort
      hypothesis, few studies have found support for paternal effort. We used two
      experiments to test the paternal-effort hypothesis in the dark fishing spider,
      Dolomedes tenebrosus. Males of this species provide themselves as a material
      contribution: they spontaneously die during copulation and are subsequently eaten
      by females. In support of the paternal-effort predictions, when females were
      allowed to consume their mating partner, we found large and significant increases
      in (1) the number, (2) the size, and (3) the survivorship of the offspring.
      Similar benefits were not seen when females were allowed to consume a cricket in
      lieu of a male, suggesting that it is the consumption of the male's body per se
      that is responsible for these fitness benefits. Together, our results suggest
      that D. tenebrosus males can benefit from self-sacrifice behavior through
      paternal effort. Such behavior may be particularly likely to evolve when high
      rates of postcopulatory cannibalism trap males into investing in their first mate
      instead of investing in acquiring additional matings and/or if strong first-male
      sperm precedence reduces the benefits of both investing in additional matings and
      paternity protection.

PMID- 27720622
TI  - Distinct Domestication Trajectories in Top-Fermenting Beer Yeasts and Wine
      Yeasts.
AB  - Beer is one of the oldest alcoholic beverages and is produced by the fermentation
      of sugars derived from starches present in cereal grains. Contrary to lager
      beers, made by bottom-fermenting strains of Saccharomyces pastorianus, a hybrid
      yeast, ale beers are closer to the ancient beer type and are fermented by S.
      cerevisiae, a top-fermenting yeast. Here, we use population genomics to
      investigate (1) the closest relatives of top-fermenting beer yeasts; (2) whether
      top-fermenting yeasts represent an independent domestication event separate from
      those already described; (3) whether single or multiple beer yeast domestication
      events can be inferred; and (4) whether top-fermenting yeasts represent non
      recombinant or recombinant lineages. Our results revealed that top-fermenting
      beer yeasts are polyphyletic, with a main clade composed of at least three
      subgroups, dominantly represented by the German, British, and wheat beer strains.
      Other beer strains were phylogenetically close to sake, wine, or bread yeasts. We
      detected genetic signatures of beer yeast domestication by investigating genes
      previously linked to brewing and using genome-wide scans. We propose that the
      emergence of the main clade of beer yeasts is related with a domestication event
      distinct from the previously known cases of wine and sake yeast domestication.
      The nucleotide diversity of the main beer clade more than doubled that of wine
      yeasts, which might be a consequence of fundamental differences in the modes of
      beer and wine yeast domestication. The higher diversity of beer strains could be
      due to the more intense and different selection regimes associated to brewing.

PMID- 27720623
TI  - Intraspinal Sensory Neurons Provide Powerful Inhibition to Motor Circuits
      Ensuring Postural Control during Locomotion.
AB  - In the vertebrate spinal cord, cerebrospinal fluid-contacting neurons (CSF-cNs)
      are GABAergic neurons whose functions are only beginning to unfold. Recent
      evidence indicates that CSF-cNs detect local spinal bending and relay this
      mechanosensory feedback information to motor circuits, yet many CSF-cN targets
      remain unknown. Using optogenetics, patterned illumination, and in vivo
      electrophysiology, we show here that CSF-cNs provide somatic inhibition to fast
      motor neurons and excitatory sensory interneurons involved in the escape circuit.
      Ventral CSF-cNs respond to longitudinal spinal contractions and induce large
      inhibitory postsynaptic currents (IPSCs) sufficient to silence spiking of their
      targets. Upon repetitive stimulation, these IPSCs promptly depress, enabling the
      mechanosensory response to the first bend to be the most effective. When CSF-cNs
      are silenced, postural control is compromised, resulting in rollovers during
      escapes. Altogether, our data demonstrate how GABAergic sensory neurons provide
      powerful inhibitory feedback to the escape circuit to maintain balance during
      active locomotion.

PMID- 27720624
TI  - Starvation-Induced Depotentiation of Bitter Taste in Drosophila.
AB  - Nutrient deprivation can lead to dramatic changes in feeding behavior, including
      acceptance of foods that are normally rejected. In flies, this behavioral shift
      depends in part on reciprocal sensitization and desensitization of sweet and
      bitter taste, respectively. However, the mechanisms for bitter taste modulation
      remain unclear. Here, we identify a set of octopaminergic/tyraminergic neurons,
      named OA-VLs, that directly modulate bitter sensory neuron output in response to
      starvation. OA-VLs are in close proximity to bitter sensory neuron axon terminals
      and show reduced tonic firing following starvation. We find that octopamine and
      tyramine potentiate bitter sensory neuron responses, suggesting that starvation
      induced reduction in OA-VL activity depotentiates bitter taste. Consistent with
      this model, artificial silencing of OA-VL activity induces a starvation-like
      reduction in bitter sensory neuron output. These results demonstrate that OA-VLs
      mediate a critical step in starvation-dependent bitter taste modulation, allowing
      flies to dynamically balance the risks associated with bitter food consumption
      against the threat of severe starvation.

PMID- 27720625
TI  - Design, construction and validation of a Plasmodium vivax microarray for the
      transcriptome profiling of clinical isolates.
AB  - High density oligonucleotide microarrays have been used on Plasmodium vivax field
      isolates to estimate whole genome expression. However, no microarray platform has
      been experimentally optimized for studying the transcriptome of field isolates.
      In the present study, we adopted both bioinformatics and experimental testing
      approaches to select best optimized probes suitable for detecting parasite
      transcripts from field samples and included them in designing a custom 15K P.
      vivax microarray. This microarray has long oligonucleotide probes (60mer) that
      were in-situ synthesized onto glass slides using Agilent SurePrint technology and
      has been developed into an 8X15K format (8 identical arrays on a single slide).
      Probes in this array were experimentally validated and represents 4180 P. vivax
      genes in sense orientation, of which 1219 genes have also probes in antisense
      orientation. Validation of the 15K array by using field samples (n=14) has shown
      99% of parasite transcript detection from any of the samples. Correlation
      analysis between duplicate probes (n=85) present in the arrays showed perfect
      correlation (r2=0.98) indicating the reproducibility. Multiple probes
      representing the same gene exhibited similar kind of expression pattern across
      the samples (positive correlation, r>=0.6). Comparison of hybridization data with
      the previous studies and quantitative real-time PCR experiments were performed to
      highlight the microarray validation procedure. This array is unique in its
      design, and results indicate that the array is sensitive and reproducible. Hence,
      this microarray could be a valuable functional genomics tool to generate reliable
      expression data from P. vivax field isolates.

PMID- 27720626
TI  - Detection of Leishmania DNA and blood meal sources in phlebotomine sand flies
      (Diptera: Psychodidae) in western of Spain: Update on distribution and risk
      factors associated.
AB  - Leishmaniosis caused by Leishmania infantum is present in Mediterranean
      countries, with high prevalence in areas of the center and south of Spain.
      However, in some regions such as Extremadura (in southwest of Spain), data has
      not been updated since 1997. The aim of this work was (i) to provide information
      about the distribution of phlebotomine sand fly species in western of Spain
      (Extremadura region), (ii) to determine risk factors for the presence of sand fly
      vectors and (iii) to detect Leishmania DNA and identify blood meal sources in
      wild caught females. During 2012-2013, sand flies were surveyed using CDC
      miniature light-traps in 13 of 20 counties in Extremadura. Specimens were
      identified morphologically and females were used for molecular detection of
      Leishmania DNA by kDNA, ITS-1 and cyt-B. In addition, blood meals origins were
      analyzed by a PCR based in vertebrate cyt b gene. A total of 1083 sand flies of
      both gender were captured and identified. Five species were collected,
      Phlebotomus perniciosus (60.76%), Sergentomyia minuta (29.92%), P. ariasi
      (7.11%), P. papatasi (1.48%) and P. sergenti (0.74%). The last three species
      constitute the first report in Badajoz, the most southern province of Extremadura
      region. Leishmania DNA was detected in three out of 435 females (one P.
      pernicious and two S. minuta). Characterization of obtained DNA sequences by
      phylogenetic analyses revealed close relatedness with Leishmania tarentolae in S.
      minuta and L. infantum in P. perniciosus. Haematic preferences showed a wide
      range of hosts, namely: swine, humans, sheep, rabbits, horses, donkeys and
      turkeys. The simultaneous presence of P. perniciosus and P. ariasi vectors, the
      analysis of blood meals, together with the detection of L. infantum and in S.
      minuta of L. tarentolae, confirms the ideal conditions for the transmission of
      this parasitosis in the western of Spain. These results improve the
      epidemiological knowledge of leishmaniosis and its vectors in this part of Spain,
      highlighting the need for ongoing entomological and parasitological surveillance.

PMID- 27720627
TI  - [Challenges in renal transplantation].
AB  - OBJECTIVES: To describe kidney transplantation surgical techniques and to propose
      strategies in high-risk recipients. MATERIAL AND METHODS: Relevant publications
      were identified through Medline (http://www.ncbi.nlm.nih.gov/) and Embase
      (http://www.embase.com/) database using the following keywords, alone or in
      association, "renal transplantation; peripheral arterial disease; obesity; third
      and fourth transplantation; robotic-assisted kidney transplant; anticoagulant
      therapy; dual kidney transplant". Articles were selected according to methods,
      language of publication and relevance. The reference lists were used to identify
      additional historical studies of interest. Both prospective and retrospective
      series, in French and English, as well as review articles and case-reports were
      selected. A total of 1949 articles were analyzed for arterial disease and
      anticoagulant therapy, 1083 for obesity, 663 for dual kidney transplants, 458 for
      third and subsequent procedures and 84 for robotic-assisted kidney
      transplantation. After careful selection, 304 publications were eligible for our
      review. RESULTS: Surgical assessment of future recipients is a pivotal step to
      anticipate technical difficulties, to interrupt clopidogrel or direct oral
      anticoagulants and to propose a revascularization procedure when necessary. Lack
      of data regarding obese recipients does not allow us to conclude about best
      surgical care or optimal timing but suggest that an early global management of
      obesity in chronic kidney disease patients is mandatory to improve access to a
      successful transplantation. In neurologic bladder and congenital anomalies,
      urodynamics and bladder function must be assessed prior to the onset of oliguria
      to intend an early treatment. Urinary diversion may be performed prior to or
      after transplantation with similar survival outcome and comparable rates of
      infections. Because of a rigorous selection of donors, the French dual kidney
      transplant program provides satisfactory outcomes, but fails in convincing
      surgical teams nationwide. Third and subsequent transplant procedures remain a
      surgical and immunological challenge, with an increased morbidity and a moderate
      decline in transplant survival only when donors are extended criteria' with
      extensive duration of waiting time between procedures. Robotic-assisted kidney
      transplantation is a recent technique requiring methodical evaluation.
      CONCLUSION: Kidney transplantation in challenging recipients implies a global
      understanding of patients' prognosis and benefits versus dialysis, in the context
      of the attribution of a valuable resource awaited by other patients on waiting
      list.

PMID- 27720628
TI  - [Simultaneous pancreas and kidney transplantation].
AB  - OBJECTIVES: To perform a State of The Art about the different aspects of pancreas
      transplantation such as indications, technical features, immunosuppressive
      strategies and outcomes of simultaneous pancreas-kidney transplantation. MATERIAL
      AND METHODS: An exhaustive systematic review of the scientific literature was
      performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase
      (http://www.embase.com) using different associations of the following keywords
      (MESH) : " pancreas transplantation; kidney transplantation; simultaneous
      pancreas-kidney transplantation; immunosuppression ". Publications obtained were
      selected based on methodology, language, date of publication (last 20 years) and
      relevance. Prospective and retrospective studies, in English or French, review
      articles; meta-analysis and guidelines were selected and analyzed. This search
      found 2736 articles. After reading titles and abstracts, 23 were included in the
      text, based on their relevance. RESULTS: These last few years, considerable
      progresses were done in optimizing indication for pancreas transplantation, as
      well as surgical improvement and a better used of immunosuppression. In the first
      part of this article, demographics, indication and pre-transplant evaluation will
      be described. The different techniques of procurement, preparation and
      transplantation will then be discussed. Finally, the results and outcomes of
      pancreas transplantation will be reported. CONCLUSIONS: Despite its morbidity,
      pancreas transplantation is the optimal treatment of end stage renal disease in
      diabetic patients under 55. Long-term results and quality of life improvement
      after pancreas transplantation are excellent. LEVEL OF EVIDENCE: NA.

PMID- 27720629
TI  - [Living kidney donation].
AB  - OBJECTIVES: To review ethical, legal and technical aspects of living kidney donor
      surgery. MATERIAL AND METHODS: An exhaustive systematic review of the scientific
      literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov)
      and Embase (http://www.embase.com) using different associations of the following
      keywords: Donor nephrectomy; Kidney paired donation; Kidney transplantation;
      Laparoscopic nephrectomy; Living donor; Organs trafficking; Robotic assisted
      nephrectomy; Vaginal extraction. French legal documents have been reviewed using
      the government portal (http://www.legifrance.gouv.fr). Articles were selected
      according to methods, language of publication and relevance. A total of 6421
      articles were identified; after careful selection, 161 publications were
      considered of interest and were eligible for our review. RESULTS: The ethical
      debate focuses on organ shortage, financial incentive, organ trafficking and the
      recent data suggesting a small but significant increase risk for late renal
      disease in donor population. Legal decisions aim to increase the number of
      kidneys available for donation, such as kidney-paired donation that faces several
      obstacles in France. Laparoscopic approach became widely used, while robotic
      assisted donor nephrectomy failed to demonstrate improved outcome as compared
      with other minimal invasive techniques. CONCLUSION: Minimally invasive living
      donor nephrectomy aims to limit side effects in the donor without increasing the
      morbidity in this specific population of healthy persons; long term surveillance
      to prevent the onset of renal disease in mandatory.

PMID- 27720630
TI  - An unusual case of Pigmented Villo-Nodular Synovitis of the second toe: A case
      report and review of literature.
AB  - Pigmented villo-nodular synovitis (PVNS) is a common disease entity particularly
      in the knee joint but its incidence in the foot is quite rare. A case of PVNS of
      the second toe that presented at the outpatient department with an insidious
      onset and slowly progressive painful swelling of the toe associated with
      stiffness is presented. The mass was subsequently excised and the diagnosis
      confirmed by histo-pathology samples. The patient's symptoms improved
      significantly after the operation. This case is one of the very few reported
      cases of PVNS involvement of flexor tendon sheath of the foot. It also signifies
      the importance of clinical suspicions based on the symptoms and examination in
      reaching to the presumptive diagnosis of the foot pathology and its confirmation
      by histo-pathological evaluation.

PMID- 27720631
TI  - Early chemotherapy discontinuation and mortality in older patients with
      metastatic bladder cancer: The AGEVIM multicenter cohort study.
AB  - PURPOSE: Median age for the diagnosis of metastatic bladder cancer (MBC) is 73
      years. The feasibility of chemotherapy in older patients is controversial. Our
      objectives were to assess associations linking age to first line chemotherapy
      regimen selection, early chemotherapy discontinuation, and 1-year mortality in
      everyday practice. MATERIALS AND METHODS: Between 1999 and 2011, 197 consecutive
      patients aged>=70 years with MBC referred to 4 hospitals were included in the
      AGEVIM multicenter cohort. At baseline, we recorded performance status (PS);
      tumor characteristics; the Charlson Comorbidity Index; and plasma creatinine,
      hemoglobin, and albumin. Early discontinuation data were available for 193
      patients, and overall 1-year mortality for 180 patients. We assessed the
      probabilities of initial cisplatin-based combination chemotherapy (CCC), early
      discontinuation (<=2 cycles), and 1-year mortality, using multivariate logistic
      regression and Cox proportional hazards modeling. RESULTS: Among the 193 patients
      (mean age: 76+/-4.3y), with 2 metastatic site in median 43.5% received CCC, 36.3%
      gemcitabine and carboplatin, and 20.2% gemcitabine alone. The probability of CCC
      decreased with age independently from sex, PS, creatinine clearance, and Charlson
      Comorbidity Index (P<0.0001), early discontinuation occurred in 24.9% of
      patients. Factors independently associated with global chemotherapy early
      discontinuation were age (adjusted odds ratioper additional year = 1.11; 95% CI:
      1.02-1.20; P = 0.01) and higher metastatic-site number (adjusted odds ratioper
      additional site = 1.45; 95% CI: 1.08-1.95; P = 0.01). The number of patients was
      too small for a robust analysis of factors associated with early chemotherapy
      discontinuation in each chemotherapy regiment subgroup. Independent predictors of
      1-year mortality (median = 9.6 mo) were early discontinuation (adjusted hazard
      ratio [aHR] = 4.77 [2.85-7.96] when PS<2 and 20.6 [9.43-44.82] when PS>=2;
      P<0.0001), albumin<35g/l (aHR = 3.06 [1.81-5.17], P = 0.0001), creatinine
      clearance<30ml/min (aHR = 2.96 [1.45-6.06], P = 0.009), and higher metastatic
      site number (aHR = 1.34 [1.14-1.56], P<0.0001). CONCLUSION: Less than half of
      older patients with MBC received initial CCC and 25% had<=2 cycles of
      chemotherapy. Older age was associated with decreased CCC prescription,
      independently from known contraindications, and with global chemotherapy early
      discontinuation, but not with 1-year mortality.

PMID- 27720632
TI  - Extended Twilight among Isogenic C. elegans Causes a Disproportionate Scaling
      between Lifespan and Health.
AB  - Although many genetic factors and lifestyle interventions are known to affect the
      mean lifespan of animal populations, the physiological variation displayed by
      individuals across their lifespans remains largely uncharacterized. Here, we use
      a custom culture apparatus to continuously monitor five aspects of aging
      physiology across hundreds of isolated Caenorhabditis elegans individuals kept in
      a constant environment from hatching until death. Aggregating these measurements
      into an overall estimate of senescence, we find two chief differences between
      longer- and shorter-lived individuals. First, though long- and short-lived
      individuals are physiologically equivalent in early adulthood, longer-lived
      individuals experience a lower rate of physiological decline throughout life.
      Second, and counter-intuitively, long-lived individuals have a disproportionately
      extended "twilight" period of low physiological function. While longer-lived
      individuals experience more overall days of good health, their proportion of good
      to bad health, and thus their average quality of life, is systematically lower
      than that of shorter-lived individuals. We conclude that, within a homogeneous
      population reared under constant conditions, the period of early-life good health
      is comparatively uniform, and the most plastic period in the aging process is end
      of-life senescence.

PMID- 27720633
TI  - Return to sports and functional results after revision anterior cruciate ligament
      reconstruction by fascia lata autograft.
AB  - INTRODUCTION: The surgical revision rate following anterior cruciate ligament
      (ACL) surgery is 3% at 2 years and 4% at 5 years. Revision ACL surgery raises the
      question of the type of graft to be used. The present study assessed return to
      sports and functional results after revision ACL reconstruction by fascia lata
      graft. The hypothesis was that fascia lata provides a reliable graft in revision
      ACL surgery. MATERIAL AND METHODS: A single-center retrospective continuous study
      included 30 sports players with a mean age of 26.8+/-8 years undergoing surgical
      revision for iterative ACL tear between 2004 and 2013. Multi-ligament lesions
      were excluded. Type and level of sports activity were assessed preoperatively,
      after primary surgery and at end of follow-up. Clinical assessment used
      subjective IKDC, Lysholm and KOOS scores. RESULTS: At a mean 4.6+/-1.6 years'
      follow-up, all patients had resumed sport activity, but only 12 with the same
      sport at the same level. Median subjective IKDC score increased from 57 [54.3;
      58.5] preoperatively to 82 [68.3; 90] at last follow-up, and Lysholm score from
      46 [42.3; 51] to 90.5 [80.8; 96.8]; KOOS score at last follow-up was 94.7 [83;
      100]. CONCLUSION: Functional results in revision ACL reconstruction by fascia
      lata graft were satisfactory, with similar return-to-sports rates as with other
      techniques. Fascia lata provides a reliable graft in revision ACL surgery. LEVEL
      OF EVIDENCE: IV, retrospective study.

PMID- 27720635
TI  - Isolated effects of external bath osmolality, solute concentration, and
      electrical charge on solute transport across articular cartilage.
AB  - The metabolic function of cartilage primarily depends on transport of solutes
      through diffusion mechanism. In the current study, we use contrast enhanced micro
      computed tomography to determine equilibrium concentration of solutes through
      different cartilage zones and solute flux in the cartilage, using osteochondral
      plugs from equine femoral condyles. Diffusion experiments were performed with two
      solutes of different charge and approximately equal molecular weight, namely
      iodixanol (neutral) and ioxaglate (charge=-1) in order to isolate the effects of
      solute's charge on diffusion. Furthermore, solute concentrations as well as bath
      osmolality were changed to isolate the effects of steric hindrance on diffusion.
      Bath concentration and bath osmolality only had minor effects on the diffusion of
      the neutral solute through cartilage at the surface, middle and deep zones,
      indicating that the diffusion of the neutral solute was mainly Fickian. The
      negatively charged solute diffused considerably slower through cartilage than the
      neutral solute, indicating a large non-Fickian contribution in the diffusion of
      charged molecules. The numerical models determined maximum solute flux in the
      superficial zone up to a factor of 2.5 lower for the negatively charged solutes
      (charge=-1) as compared to the neutral solutes confirming the importance of
      charge-matrix interaction in diffusion of molecules across cartilage.

PMID- 27720636
TI  - Design and biomechanical study of a novel adjustable hemipelvic prosthesis.
AB  - A pelvic endoprosthesis is commonly used in orthopedic surgeries to reconstruct
      the pelvis after internal hemipelvectomy. This study presents the detailed design
      of a novel type I+II+III adjustable hemipelvic prosthesis based on the
      geometrical features of massive human pelvises. Finite element analysis is
      conducted to estimate the biomechanical performance of the newly designed
      adjustable hemipelvic prosthesis. Detailed numerical models of the natural and
      reconstructed pelvises including related soft tissues are developed. Hip contact
      forces during normal walking, which is one of the most frequent dynamic
      activities in daily living, are imposed on the pelvis. Results show that the peak
      stress observed in the reconstructed pelvis model is still within a low and
      elastic range below the yielding strength of the cortical bone and Ti6Al4V. No
      significant difference of the stress transferring route, displacement
      distributions and principal stress vectors is observed between the reconstructed
      and natural pelvises. The results indicate that the load transferring function of
      the partially resected pelvis is able to be reliably recovered by the adjustable
      hemipelvic prosthesis. The principal stress vectors in both pelvis models predict
      that bone absorption may not apparently occur in the long run. Long-term
      biomechanical performance of this newly designed prosthesis may be stability.

PMID- 27720634
TI  - Coarse-grained simulations of hemolytic peptide delta-lysin interacting with a
      POPC bilayer.
AB  - delta-lysin, secreted by a Gram-positive bacterium Staphylococcus aureus, is a 26
      residue membrane active peptide that shares many common features with
      antimicrobial peptides (AMPs). However, it possesses a few unique features that
      differentiate itself from typical AMPs. In particular, delta-lysin has zero net
      charge, even though it has many charged residues, and it preferentially lyses
      eukaryotic cells over bacterial cells. Here, we present the results of coarse
      grained molecular dynamics simulations of delta-lysin interacting with a
      zwitterionic membrane over a wide range of peptide concentrations. When the
      peptides concentration is low, spontaneous dimerization of peptides is observed
      on the membrane surface, but deep insertion of peptides or pore formation was not
      observed. However, the calculated free energy of peptide insertion suggests that
      a small fraction of peptides is likely to be present inside the membrane at the
      peptide concentrations typically seen in dye efflux experiments. When the
      simulations with multiple peptides are carried out with a single pre-inserted
      transmembrane peptide, spontaneous pore formation occurs with a peptide-to-lipid
      ratio (P/L) as low as P/L=1:42. Inter-peptide salt bridges among the
      transmembrane peptides seem to play a role in creating compact pores with very
      low level of hydration. More importantly, the transmembrane peptides making up
      the pore are constantly pushed to the opposite side of the membrane when the mass
      imbalance between the two sides of membrane is significant. Thus, the pore is
      very dynamic, allowing multiple peptides to translocate across the membrane
      simultaneously.

PMID- 27720637
TI  - Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready
      for efficacy clinical trials?
AB  - Intraspinal stem cell (SC) transplantation represents a new therapeutic approach
      for amyotrophic lateral sclerosis (ALS) clinical trials. There are considerable
      difficulties in designing future efficacy trials, some related to the field of
      ALS and some that are specific to SCs or the mode of delivery. In October 2015,
      the most controversial points on SC transplantation were addressed during an
      international workshop intended to bring together international SC and ALS
      researchers in a public discussion on a topic for which expertise is limited.
      During the meeting, a discussion was started on the basic structure of the ideal
      clinical trial testing the efficacy and safety of SC transplantation. The current
      document includes a number of consensus points reflecting the design of phase
      II/III clinical trials.

PMID- 27720638
TI  - Genetic modification of H2AX renders mesenchymal stromal cell-derived dopamine
      neurons more resistant to DNA damage and subsequent apoptosis.
AB  - BACKGROUND AIMS: Aberrant production of reactive oxygen species (ROS) and its
      impact on the integrity of genomic DNA have been considered one of the major risk
      factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem
      cell transplantation as a strategy to replenish new functional neurons has great
      potential for PD treatment. However, limited survival of stem cells post
      transplantation has always been an obstacle ascribed to the existence of
      neurotoxic environment in PD patients. METHODS: To improve the survival of
      transplanted stem cells for PD treatment, we explored a new strategy based on the
      function of the H2AX gene (H2A histone family, member X) in determination of DNA
      repair and cell apoptosis. We introduced a mutant form Y142F of H2AX into
      dopamine (DA) neuron-like cells differentiated from bone marrow-derived
      mesenchymal stromal cells (BMSCs). RESULTS: Expression of H2AX(Y142F) renders DA
      neuron-like cells more resistant to DNA damage and subsequent cell death induced
      by ultraviolet irradiation and 1-methyl-4-phenylpyridinium (MPP+) treatment.
      DISCUSSION: This is a meaningful attempt to improve the sustainability of BMSC
      derived dopamine neurons under a brain neurotoxic environment. Further studies
      are needed to evaluate the implications of our findings in stem cell therapy for
      PD and related diseases.

PMID- 27720639
TI  - Irradiation of breast cancer cells enhances CXCL16 ligand expression and induces
      the migration of natural killer cells expressing the CXCR6 receptor.
AB  - BACKGROUND AIMS: Few studies have examined the migration pattern of natural
      killer (NK) cells, especially after radiation treatment for cancer. We
      investigated whether irradiation can modulate the expression of chemokines in
      cancer cells and the migration of NK cells to irradiated tumor cells. METHODS:
      The expression of chemokine receptors (CXCR3, CXCR4 and CXCR6) on interleukin-2
      (IL-2)/IL-15-activated NK cells was assessed using flow cytometry. Related
      chemokine ligands (CXCL11, CXCL12 and CXCL16) in human breast cancer cell lines
      (MCF7, SKBR3 and MDA-MB231) irradiated at various doses were assessed using
      reverse transcription-polymerase chain reaction (RT-PCR), fluorescence-activated
      cell sorting (FACS) and enzyme-linked immunosorbent assay (ELISA). The cell-free
      culture supernatant was collected 96 h after irradiation of breast cancer cell
      lines for migration and blocking assays. RESULTS: The activated NK cells
      expressed CXCR6. Expression of the CXCR6 ligand CXCL16 increased in a time- and
      dose-dependent manner in all analyzed cancer cell lines. CXCL16 expression was
      statistically significantly enhanced in all breast cancer cell lines on day 3
      after 20 Gy irradiation. Activated NK cells migration correlated with CXCL16
      concentration (R2 = 0.91; P <0.0001). Significantly enhanced migration of NK
      cells to irradiated cancer cells was observed for a dose of 20 Gy in MCF7 (P =
      0.043) and SKBR3 (P = 0.043) cells, but not in MDA-MB231 (P = 0.225) cells. A
      blocking assay using a CXCR6 antibody showed a significant decrease in the
      migration of activated NK cells in all cancer cell lines. CONCLUSIONS: Our data
      indicate that irradiation induces CXCL16 chemokine expression in cancer cells and
      enhances the migration of activated NK cells expressing CXCR6 to irradiated
      breast cancer cells. These results suggest that radiation would improve the anti
      tumor effect of NK cells through enhanced migration of NK cells to tumor site for
      the treatment of patients with breast cancer.

PMID- 27720641
TI  - Magnitude and causes of loss to follow-up among patients with viral hepatitis at
      a tertiary care hospital in Saudi Arabia.
AB  - BACKGROUND: Non-adherence with recommended follow-up visits is a major barrier
      for completing treatment of viral hepatitis and is consequently associated with
      unfavorable outcomes of health services. OBJECTIVES: To estimate the magnitude
      and identify perceived reasons and patient characteristics associated with loss
      to follow-up in a tertiary care setting. METHODS: A two-step cross-sectional
      study design was used, including a chart review (2011) followed by phone survey
      (2012). Loss to follow-up was recorded among those who were diagnosed with
      hepatitis B (HBV) or C (HCV) during 2009-2010 but never returned for
      recommended/scheduled follow-up appointment(s). RESULTS: A total of 328 patients
      (202 HBV and 126 HCV) were included in the current analysis. The average age was
      49.6+/-17.9years, and 57% were males. Out of 328, 131 (40%) were not advised to
      do follow-up, and 98 (30%) were not doing follow-up. Perceived reasons for loss
      to follow-up were as follows: unaware that a follow-up appointment was scheduled
      (69%), never informed of need for follow-up by healthcare provider (15%),
      personal belief that follow-up was not necessary (9%), logistical reasons (3%)
      and other reasons (5%). Loss to follow-up was higher among those who had been
      diagnosed with HBV, referred by non-liver-related specialty, never advised to
      follow-up, unaware of their diagnosis, incorrectly identified their type of
      hepatitis, lacking hepatitis complications, having full medical coverage,
      pregnant, and those with low knowledge or negative attitude towards hepatitis.
      CONCLUSIONS: Loss to follow-up is a significant problem among patients with
      hepatitis in a tertiary care center, with several patient and system failures
      being implicated.

PMID- 27720640
TI  - Endophilin-A Deficiency Induces the Foxo3a-Fbxo32 Network in the Brain and Causes
      Dysregulation of Autophagy and the Ubiquitin-Proteasome System.
AB  - Endophilin-A, a well-characterized endocytic adaptor essential for synaptic
      vesicle recycling, has recently been linked to neurodegeneration. We report here
      that endophilin-A deficiency results in impaired movement, age-dependent ataxia,
      and neurodegeneration in mice. Transcriptional analysis of endophilin-A mutant
      mice, complemented by proteomics, highlighted ataxia- and protein-homeostasis
      related genes and revealed upregulation of the E3-ubiquitin ligase FBXO32/atrogin
      1 and its transcription factor FOXO3A. FBXO32 overexpression triggers apoptosis
      in cultured cells and neurons but, remarkably, coexpression of endophilin-A
      rescues it. FBXO32 interacts with all three endophilin-A proteins. Similarly to
      endophilin-A, FBXO32 tubulates membranes and localizes on clathrin-coated
      structures. Additionally, FBXO32 and endophilin-A are necessary for autophagosome
      formation, and both colocalize transiently with autophagosomes. Our results point
      to a role for endophilin-A proteins in autophagy and protein degradation,
      processes that are impaired in their absence, potentially contributing to
      neurodegeneration and ataxia.

PMID- 27720642
TI  - RNA Sequence Context Effects Measured In Vitro Predict In Vivo Protein Binding
      and Regulation.
AB  - Many RNA binding proteins (RBPs) bind specific RNA sequence motifs, but only a
      small fraction (~15%-40%) of RBP motif occurrences are occupied in vivo. To
      determine which contextual features discriminate between bound and unbound
      motifs, we performed an in vitro binding assay using 12,000 mouse RNA sequences
      with the RBPs MBNL1 and RBFOX2. Surprisingly, the strength of binding to motif
      occurrences in vitro was significantly correlated with in vivo binding,
      developmental regulation, and evolutionary age of alternative splicing. Multiple
      lines of evidence indicate that the primary context effect that affects binding
      in vitro and in vivo is RNA secondary structure. Large-scale combinatorial
      mutagenesis of unfavorable sequence contexts revealed a consistent pattern
      whereby mutations that increased motif accessibility improved protein binding and
      regulatory activity. Our results indicate widespread inhibition of motif binding
      by local RNA secondary structure and suggest that mutations that alter sequence
      context commonly affect RBP binding and regulation.

PMID- 27720643
TI  - Molecular Architecture of SF3b and Structural Consequences of Its Cancer-Related
      Mutations.
AB  - SF3b is a heptameric protein complex of the U2 small nuclear ribonucleoprotein
      (snRNP) that is essential for pre-mRNA splicing. Mutations in the largest SF3b
      subunit, SF3B1/SF3b155, are linked to cancer and lead to alternative branch site
      (BS) selection. Here we report the crystal structure of a human SF3b core
      complex, revealing how the distinctive conformation of SF3b155's HEAT domain is
      maintained by multiple contacts with SF3b130, SF3b10, and SF3b14b. Protein
      protein crosslinking enabled the localization of the BS-binding proteins p14 and
      U2AF65 within SF3b155's HEAT-repeat superhelix, which together with SF3b14b forms
      a composite RNA-binding platform. SF3b155 residues, the mutation of which leads
      to cancer, contribute to the tertiary structure of the HEAT superhelix and its
      surface properties in the proximity of p14 and U2AF65. The molecular architecture
      of SF3b reveals the spatial organization of cancer-related SF3b155 mutations and
      advances our understanding of their effects on SF3b structure and function.

PMID- 27720647
TI  - Sanger Confirmation Is Required to Achieve Optimal Sensitivity and Specificity in
      Next-Generation Sequencing Panel Testing.
AB  - Next-generation sequencing (NGS) has rapidly replaced Sanger sequencing as the
      method of choice for diagnostic gene-panel testing. For hereditary-cancer
      testing, the technical sensitivity and specificity of the assay are paramount as
      clinicians use results to make important clinical management and treatment
      decisions. There is significant debate within the diagnostics community regarding
      the necessity of confirming NGS variant calls by Sanger sequencing, considering
      that numerous laboratories report having 100% specificity from the NGS data
      alone. Here we report our results from 20,000 hereditary-cancer NGS panels
      spanning 47 genes, in which all 7845 nonpolymorphic variants were Sanger-
      sequenced. Of these, 98.7% were concordant between NGS and Sanger sequencing and
      1.3% were identified as NGS false-positives, located mainly in complex genomic
      regions (A/T-rich regions, G/C-rich regions, homopolymer stretches, and
      pseudogene regions). Simulating a false-positive rate of zero by adjusting the
      variant-calling quality-score thresholds decreased the sensitivity of the assay
      from 100% to 97.8%, resulting in the missed detection of 176 Sanger-confirmed
      variants, the majority in complex genomic regions (n = 114) and mosaic mutations
      (n = 7). The data illustrate the importance of setting quality thresholds for
      panel testing only after thousands of samples have been processed and the
      necessity of Sanger confirmation of NGS variants to maintain the highest possible
      sensitivity.

PMID- 27720644
TI  - Single-Molecule Imaging Reveals that Rad4 Employs a Dynamic DNA Damage
      Recognition Process.
AB  - Nucleotide excision repair (NER) is an evolutionarily conserved mechanism that
      processes helix-destabilizing and/or -distorting DNA lesions, such as UV-induced
      photoproducts. Here, we investigate the dynamic protein-DNA interactions during
      the damage recognition step using single-molecule fluorescence microscopy.
      Quantum dot-labeled Rad4-Rad23 (yeast XPC-RAD23B ortholog) forms non-motile
      complexes or conducts a one-dimensional search via either random diffusion or
      constrained motion. Atomic force microcopy analysis of Rad4 with the beta-hairpin
      domain 3 (BHD3) deleted reveals that this motif is non-essential for damage
      specific binding and DNA bending. Furthermore, we find that deletion of seven
      residues in the tip of beta-hairpin in BHD3 increases Rad4-Rad23 constrained
      motion at the expense of stable binding at sites of DNA lesions, without
      diminishing cellular UV resistance or photoproduct repair in vivo. These results
      suggest a distinct intermediate in the damage recognition process during NER,
      allowing dynamic DNA damage detection at a distance.

PMID- 27720646
TI  - Pairing beyond the Seed Supports MicroRNA Targeting Specificity.
AB  - To identify endogenous miRNA-target sites, we isolated AGO-bound RNAs from
      Caenorhabditis elegans by individual-nucleotide resolution crosslinking
      immunoprecipitation (iCLIP), which fortuitously also produced miRNA-target
      chimeric reads. Through the analysis of thousands of reproducible chimeras,
      pairing to the miRNA seed emerged as the predominant motif associated with
      functional interactions. Unexpectedly, we discovered that additional pairing to
      3' sequences is prevalent in the majority of target sites and leads to specific
      targeting by members of miRNA families. By editing an endogenous target site, we
      demonstrate that 3' pairing determines targeting by specific miRNA family members
      and that seed pairing is not always sufficient for functional target
      interactions. Finally, we present a simplified method, chimera PCR (ChimP), for
      the detection of specific miRNA-target interactions. Overall, our analysis
      revealed that sequences in the 5' as well as the 3' regions of a miRNA provide
      the information necessary for stable and specific miRNA-target interactions in
      vivo.

PMID- 27720645
TI  - SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein
      Interactomes.
AB  - RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA
      binding proteins (RBPs), many of which lack characterized RNA binding domains.
      Approaches to expand the RBP repertoire to discover non-canonical RBPs are
      currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic
      RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins
      interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs.
      This motivated SONAR, a computational approach that predicts RNA binding activity
      by analyzing large-scale affinity precipitation-MS protein-protein interactomes.
      Without relying on sequence or structure information, SONAR identifies 1,923
      human, 489 fly, and 745 yeast RBPs, including over 100 human candidate RBPs that
      contain zinc finger domains. Enhanced CLIP confirms RNA binding activity and
      identifies transcriptome-wide RNA binding sites for SONAR-predicted RBPs,
      revealing unexpected RNA binding activity for disease-relevant proteins and DNA
      binding proteins.

PMID- 27720648
TI  - Common variant of PDZ domain containing 1 (PDZK1) gene is associated with gout
      susceptibility: A replication study and meta-analysis in Japanese population.
AB  - PDZ domain containing 1 (PDZK1) is a scaffold protein that organizes a
      transportsome and regulates several transporters' functions including urate and
      drug transporters. Therefore, PDZK1 in renal proximal tubules may affect serum
      uric acid levels through PDZK1-binding renal urate transporters. Two previous
      studies in Japanese male population reported that a PDZK1 single nucleotide
      polymorphism (SNP), rs12129861, was not associated with gout. In the present
      study, we performed a further association analysis between gout and rs12129861 in
      a different large-scale Japanese male population and a meta-analysis with
      previous Japanese population studies. We genotyped rs12129861 in 1210 gout cases
      and 1224 controls of a Japanese male population by TaqMan assay. As a result, we
      showed that rs12129861 was significantly associated with gout susceptibility (P =
      0.016, odds ratio [OR] = 0.80, 95% confidence interval [CI] 0.67-0.96). The
      result of the meta-analysis among Japanese populations also showed a significant
      association (P = 0.013, OR = 0.85, 95%CI 0.75-0.97). Our findings show the
      significant association between gout susceptibility and common variant of PDZK1
      which reportedly regulates the functions of urate transporters in the urate
      transportsome.

PMID- 27720649
TI  - Clinicopathologic evaluation of malignancy adjacent to dental implants.
AB  - OBJECTIVE: The aim of this study was to describe a new case series of peri
      implant malignancy, review the literature, and discuss the implications of
      malignancies resembling peri-implantitis. STUDY DESIGN: This study was a
      retrospective analysis of cases from 2000 to 2016. RESULTS: Seven patients (two
      males and five females), aged 44 to 89 years, were included, representing 1.5% of
      oral malignancy cases. Five cases were squamous carcinoma, one of basal cell
      carcinoma, and one of carcinoma of metastatic origin. Six cases presented with
      nonulcerated overgrowth, with bone loss in three and massive osteolysis in one.
      Misinterpretation as peri-implantitis delayed diagnosis in six cases. Risk
      factors included previous oral malignancy (2), potentially malignant conditions
      (2), and smoking (1). Of the 47 cases in the English language literature, 85%
      were squamous cell carcinoma and 8.5% had distant metastasis. Most cases had one
      or more risk factors. CONCLUSIONS: Peri-implant malignancy may represent up to
      1.5% of oral malignancy cases. Clinical features imitating peri-implantitis may
      delay diagnosis. Lesions failing to respond to treatment, especially in patients
      with pre-existing risk factors, should significantly increase suspicion.
      Histopathology is crucial for diagnosis.

PMID- 27720650
TI  - Clinicobiochemical evaluation of turmeric with black pepper and nigella sativa in
      management of oral submucous fibrosis-a double-blind, randomized preliminary
      study.
AB  - OBJECTIVE: To investigate the effectiveness of turmeric with black pepper and
      nigella sativa in oral submucous fibrosis (OSMF). STUDY DESIGN: Forty OSMF
      patients were randomly divided into two groups. The study was performed under a
      double-blind, randomized design. Group A received turmeric with black pepper and
      group B received nigella sativa for 3 months. Clinical evaluation was done every
      15 days. Patients' serum superoxide dismutase (SOD) levels were assessed before
      and after treatment and also compared with healthy controls. The response to
      treatment was analyzed using analysis of variance, paired t test, and unpaired t
      test. RESULTS: After the treatment, groups A and B showed 3.85 +/- 0.22 mm and
      3.6 +/- 0.07 mm improvement in mouth opening, respectively (P < .01); 87.90% and
      78.91% reduction in burning sensation, respectively (P < .01); and +0.62 U/mL and
      +0.74 U/mL improvement in serum SOD levels, respectively (P < .05). The maximum
      mouth opening achieved was 8 mm in group A and 7 mm in group B. The mean
      pretreatment SOD level for controls and patients was 3.61 +/- 0.24 U/mL in group
      A and 2.63 +/- 0.18 U/mL in group B. CONCLUSION: Turmeric with black pepper and
      nigella sativa improved mouth opening, burning sensation, and SOD levels in the
      present OSMF study patients; however, further investigations are needed.

PMID- 27720651
TI  - Second primary cancer after index head and neck squamous cell carcinoma in
      Northern China.
AB  - OBJECTIVE: To evaluate the clinicopathologic features, prognostic factors, and
      management of patients in the North Chinese population with head and neck
      squamous cell carcinoma (HNSCC) who developed a second primary malignancy (SPM).
      METHODS: This was a retrospective study including 1818 eligible patients between
      June 1999 and April 2011. RESULTS: A total of 188 HNSCC patients developed SPM.
      Multiple oral dysplastic lesions (MODLs) (P < .001) were among the risk factors
      for occurrence of SPM. However, MODLs were closely associated with many mild
      pathologic features, such as early T stage (P < .001), early N stage (P = .036),
      good pathologic differentiation (P < .001), and mild growth pattern (P < .001).
      Interestingly, multivariate survival analysis showed that SPM patients had a
      better prognosis if they had the characteristics of MODLs (P = .020).
      CONCLUSIONS: MODLs were a crucial risk factor leading to the occurrence of oral
      SPM after an index HNSCC in patients in Northern China. However, SPM patients
      with the characteristics of MODLs had a better prognosis.

PMID- 27720652
TI  - In vivo reflectance confocal microscopy for evaluating melanoma of the lip and
      its differential diagnoses.
AB  - OBJECTIVE: To improve prebiopsy diagnostic accuracy and surgical management of
      pigmented appearing lesions on the lips, particularly melanoma, using in vivo
      reflectance confocal microscopy (RCM). STUDY DESIGN: Prospective case series over
      a 12-month period between 2015 and 2016. The setting was two specialist
      dermatology referral centers with expertise in confocal microscopy. The study
      population was a consecutive sample of patients with pigmentation of the lip for
      which the cause was uncertain clinically, whose differential diagnosis included
      melanoma, and who had undergone both in vivo RCM and subsequent biopsy. The
      outcome measures were RCM features, dermoscopy features, and histopathological
      diagnosis. Results were reported by descriptive analysis and correlations made
      between RCM features and histopathology. RESULTS: Eight patients were recruited
      for the study. In vivo RCM facilitated the targeting of small biopsies to
      identify two in situ oral melanoma recurrences and successfully mapped an in situ
      oral melanoma before wide excision. Suprabasal dendritic pagetoid cells and
      epidermal disarray on RCM were useful indicators for in situ melanoma of the lip.
      Previously described dermoscopy features for mucosal melanoma were not very
      helpful in diagnosing melanoma in our series. Challenges included evaluating
      inflamed lesions with pigment incontinence. CONCLUSIONS: RCM can assist in the
      diagnosis and management of pigmented lip lesions, but additional studies are
      required to further evaluate these initial observations.

PMID- 27720653
TI  - Oral medicine specialty?

PMID- 27720654
TI  - Response to the article "Comparison of the performance of intraoral X-ray sensors
      using objective image quality assessment".

PMID- 27720655
TI  - Osteoblast-like cells with different embryologic origins behave differently in
      increasing zoledronic acid concentrations: a pilot study in pigs.
AB  - OBJECTIVE: We compared the intraindividual effects of increasing zoledronic acid
      (ZA) concentrations on osteoblast-like cells with different embryologic origins.
      STUDY DESIGN: Cultured osteoblast-like cells from mandible and iliac crest bone
      samples of domestic pigs were exposed to increasing concentrations of ZA (0, 10
      8, 10-6, and 10-4 M). Proliferation was assessed by cell counting. Receptor
      activator of nuclear factor kB ligand and osteoprotegerin (OPG) messenger RNA
      expression were assessed at 0, 1, 4, 7, and 10 days. RESULTS: The OPG expression
      level was higher in the iliac crest than in the mandible. Neither ZA
      concentration nor the cells' origin affected the expression of receptor activator
      of nuclear factor kB ligand. At 10-6 M, OPG expression from both locations
      reached the same level after 7 days of cultivation, as OPG expression increased
      to a greater extent in the mandible in comparison to the iliac crest. CONCLUSION:
      Cultured mandibular osteoblast-like cells reacted more sensitively to high ZA
      concentrations than did osteoblast-like cells from the iliac crest.

PMID- 27720657
TI  - Tumor mass in the palate after bone marrow transplantation.

PMID- 27720656
TI  - MicroRNA-375 as a biomarker for malignant transformation in oral lesions.
AB  - OBJECTIVE: Malignant transformation of oral premalignant lesions is the key
      process in the progression to oral squamous cell carcinoma (OSCC). Previously, we
      identified miR-7 and miR-21 as candidate oncogenes and miR-375 and miR-494 as
      candidate tumor suppressors in OSCC. We aim to evaluate these microRNAs as
      biomarkers of malignant transformation in oral premalignant lesions. STUDY
      DESIGN: Formalin-fixed, paraffin-embedded samples from progressive premalignant
      lesions and paired sequential OSCC tumors at the same site were obtained from
      same patients (n = 31). Total RNA was extracted and analyzed for microRNA levels
      using real-time polymerase chain reaction. RESULTS: MiR-375 expression in
      progressive lesions was clearly lower than in nonprogressive control lesions
      (average eightfold difference, P = .0004). Furthermore, the expression of miR-375
      decreased significantly after the progression from premalignant lesion to OSCC (P
      < .0001). Receiver operating characteristic curve analysis revealed that miR-375
      was able to differentiate between progressive and nonprogressive premalignant
      lesions (P < .0001). CONCLUSIONS: MiR-375 downregulation in oral premalignant
      lesions is associated with a higher risk of malignant transformation.

PMID- 27720658
TI  - "A randomized double-blind, multiple-arm trial comparing the efficacy of
      submucosal injections of hyaluronidase, dexamethasone, and combination of
      dexamethasone and hyaluronidase in the management of oral submucous fibrosis"-a
      commentary.

PMID- 27720659
TI  - A randomized control trial measuring the effectiveness of a mouth-exercising
      device for mucosal burning in oral submucous fibrosis.
AB  - OBJECTIVES: To evaluate effect of ice-cream stick exercise regimen with or
      without a mouth-exercising device (MED) on mucosal burning sensation in oral
      submucous fibrosis. STUDY DESIGN: In total, 282 patients with oral submucous
      fibrosis were treated with topical corticosteroid and oral antioxidant and the
      ice-cream stick exercise regimen. Patients in subgroups A1, A2, and A3 were
      additionally given a new MED. Patients in subgroups A1 and B1 patients with
      interincisal distance (IID) of 20 to 35 mm were managed without any additional
      therapy; patients in subgroups A2 and B2 with IID of 20 to 35 mm were
      additionally managed with intralesional injections; and those in subgroups A3 and
      B3 with IID less than 20 mm were managed surgically. Subjective evaluation of
      decrease in the oral mucosal burning was measured on a visual analogue scale
      (VAS). Analysis of variance and Tukey's multiple post hoc analysis were carried
      out to present the results. RESULTS: Patients using the MED, that is, subgroups
      A1, A2, and A3, showed reduction in burning sensation in the range of 64.8% to
      71.1% and 27.8% to 30.9%, whereas in subgroups B1, B2, and B3, reduction in
      burning sensation ranged from 64.7% to 69.9% and from 29.3% to 38.6% after 6
      months. The wo-way analysis of variance indicated statistically significant
      results in changes in initial VAS scores to 6-monthly VAS scores between MED
      users and non-MED users. CONCLUSIONS: The MED helps to enhance the rate of
      reduction of mucosal burning sensation, in addition to the conventional ice-cream
      stick regimen, as an adjunct to local and surgical treatment.

PMID- 27720660
TI  - Mandibular changes on panoramic imaging after head and neck radiotherapy: a
      commentary.

PMID- 27720661
TI  - Comparison of intraoperative blood loss between four different surgical
      procedures in the treatment of bimaxillary protrusion.
AB  - OBJECTIVE: This study was aimed at investigating the correlation between
      intraoperative blood loss and operation-related factors in the treatment of
      bimaxillary protrusion with four different procedures. STUDY DESIGN: Ninety-four
      patients were separated into the following four surgical groups: group 1:
      anterior subapical osteotomy of the maxilla (ASO Mx) + bilateral parasymphyseal
      osteotomy of the mandible (BPsO Md) + genioplasty (GeP); group 2: ASO Mx + BPsO
      Md; group 3: ASO Mx + ASO Md + GeP; and group 4: ASO Mx + ASO Md. Patient- and
      operation-related factors (age, intraoperative blood loss, operation time, and
      preoperative and postoperative blood parameters) were compared among the four
      groups. RESULTS: The mean operation time and intraoperative blood loss were 438.7
      minutes and 369.9 mL in group 1; 432.5 minutes and 356.5 mL in group 2; 393.3
      minutes and 387.3 mL in group 3; and 353.5 minutes and 289.5 mL in group 4.
      Intergroup differences in intraoperative blood loss were not significant. A
      significant correlation between intraoperative blood loss and operation time was
      found in group 4 but not in the other groups. CONCLUSIONS: No significant
      differences in blood loss were found among the four different surgical procedures
      in the treatment of bimaxillary protrusion.

PMID- 27720662
TI  - Inappropriate Fentanyl Prescribing Among Nursing Home Residents in the United
      States.
AB  - OBJECTIVE: We quantified transdermal fentanyl prescribing in elderly nursing home
      residents without prior opioid use or persistent pain, and the association of
      individual and facility traits with opioid-naive prescribing. DESIGN: Cross
      sectional study. SETTING: Linked Minimum Data Set (MDS) assessments; Online
      Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims.
      PARTICIPANTS: From a cross-section of all long-stay US nursing home residents in
      2008 with an MDS assessment and Medicare Part D enrollment, we identified
      individuals (>=65 years old) who initiated transdermal fentanyl, excluding those
      with Alzheimer disease, severe cognitive impairment, cancer, or receipt of
      hospice care. MEASUREMENTS: We used Medicare Part D to select beneficiaries
      initiating transdermal fentanyl in 2008 and determined whether they were "opioid
      naive," defined as no opioid dispensing during the previous 60 days. We obtained
      resident and facility characteristics from MDS and OSCAR records and defined
      persistent pain as moderate-to-severe, daily pain on consecutive MDS assessments
      at least 90 days apart. We estimated associations of patient and facility
      attributes and opioid-naive fentanyl initiation using multilevel mixed effects
      logistic regression modeling. RESULTS: Among 17,052 residents initiating
      transdermal fentanyl, 6190 (36.3%) were opioid-naive and 15,659 (91.8%) did not
      have persistent pain. In the regression analysis with adjustments, residents who
      were older (ages >=95 odds ratio [OR] 1.69, 95% confidence interval [CI] 1.46
      1.95) or more cognitively impaired (moderate-to-severe cognitive impairment, OR
      1.99, 95% CI 1.73-2.29) were more likely to initiate transdermal fentanyl without
      prior opioid use. CONCLUSION: Most nursing home residents initiating transdermal
      fentanyl did not have persistent pain and many were opioid-naive. Changes in
      prescribing practices may be necessary to ensure Food and Drug Administration
      warnings are followed, particularly for vulnerable subgroups, such as the
      cognitively impaired.

PMID- 27720663
TI  - Performance-Based Assessment of Instrumental Activities of Daily Living:
      Validation of the Sydney Test of Activities of Daily Living in Memory Disorders
      (STAM).
AB  - OBJECTIVES: The distinction between dementia and mild cognitive impairment (MCI)
      relies upon the evaluation of independence in instrumental activities of daily
      living (IADL). Self- and informant reports are prone to bias. Clinician-based
      performance tests are limited by long administration times, restricted access, or
      inadequate validation. To close this gap, we developed and validated a
      performance-based measure of IADL, the Sydney Test of Activities of Daily Living
      in Memory Disorders (STAM). DESIGN: Prospective cohort study (Sydney Memory and
      Ageing Study). SETTING: Eastern Suburbs, Sydney, Australia. PARTICIPANTS: 554
      community-dwelling individuals (54% female) aged 76 and older with normal
      cognition, MCI, or dementia. MEASUREMENTS: Activities of daily living were
      assessed with the STAM, administered by trained psychologists, and the informant
      based Bayer-Activities of Daily Living Scale (B-ADL). Depressive symptoms were
      measured with the Geriatric Depression Scale (15-item version). Cognitive
      function was assessed with a comprehensive neuropsychological test battery.
      Consensus diagnoses of MCI and dementia were made independently of STAM scores.
      RESULTS: The STAM showed high interrater reliability (r = 0.854) and test-retest
      reliability (r = 0.832). It discriminated significantly between the diagnostic
      groups of normal cognition, MCI, and dementia with areas under the curves ranging
      from 0.723 to 0.948. A score of 26.5 discriminated between dementia and
      nondementia with a sensitivity of 0.831 and a specificity of 0.864. Correlations
      were low with education (r = 0.230) and depressive symptoms (r = -0.179),
      moderate with the B-ADL (r = -0.332), and high with cognition (ranging from r =
      0.511 to r = 0.594). The mean time to complete the STAM was 16 minutes.
      CONCLUSIONS: The STAM has good psychometric properties. It can be used to
      differentiate between normal cognition, MCI, and dementia and can be a helpful
      tool for diagnostic classification both in clinical practice and research.

PMID- 27720664
TI  - Pharmacological management of acute kidney injury and chronic kidney disease in
      neonates.
AB  - Both acute kidney injury (AKI) and chronic kidney disease (CKD) are seen more
      frequently in the neonatal intensive care unit (NICU) as advances in supportive
      care improve the survival of critically ill infants as well as those with severe,
      congenital kidney and urinary tract anomalies. Many aspects of the infant's care,
      including fluid balance, electrolyte and mineral homeostasis, acid-base balance,
      and growth and nutrition require close monitoring by and collaboration among
      neonatologists, nephrologists, dieticians, and pharmacologists. This educational
      review summarizes the therapies widely used for neonates with AKI and CKD. Use of
      these therapies is extrapolated from data in older children and adults or based
      on clinical experience and case series. There is a critical need for more
      research on the use of therapies in infants with kidney disease as well as for
      the development of drug delivery systems and preparations scaled more
      appropriately for these small patients.

PMID- 27720665
TI  - The Road to 25*25: Update on WHF CVD Roadmaps.

PMID- 27720666
TI  - Primary repair of the anterior cruciate ligament: A paradigm shift.
AB  - Over the last century, many surgical treatments have been developed in the
      orthopedic field, including treatments of anterior cruciate ligament (ACL)
      injuries. These treatments ideally evolve in a process of trial and error with
      prospective comparison of new treatments to the current treatment standard.
      However, these evolutions are sometimes not linear and periodically undergo
      paradigm shifts. In this article, we review the evolution of ACL treatment and
      explain how it underwent a paradigm shift. Open primary ACL repair was the most
      common treatment in the 1970s and 1980s, but because multiple studies noted
      deterioration of outcomes at mid-term follow-up, in addition to several
      randomized clinical trials (RCTs) that noted better outcomes following ACL
      reconstruction, the open primary repair technique was abandoned. At the end of
      the primary repair era, however, several studies showed that outcomes of open
      primary repair were good to excellent and did not deteriorate when this technique
      was selectively performed in patients with proximal ACL tears, whereas primary
      repair led to disappointing and unpredictable results in patients with mid
      substance tears. Unfortunately, enrollment of patients in the aforementioned RCTs
      was already finished, ultimately leading to abandoning of open primary repair,
      despite the advantages of ligament preservation. In this review, we discuss (I)
      why the evolution of ACL treatment underwent a paradigm shift, (II) which factors
      may have played a role in this and (III) what the future role of arthroscopic
      primary ACL repair is in the evolution of ACL treatments.

PMID- 27720667
TI  - Will TAVI Be the Standard of Care in the Treatment of Aortic Stenosis?

PMID- 27720668
TI  - Endovascular Treatment of a Complicated Acute Type B Aortic Dissection in a
      Patient With Aortic Coarctation.

PMID- 27720669
TI  - 13C dynamic nuclear polarization for measuring metabolic flux in endothelial
      progenitor cells.
AB  - Endothelial progenitor cells (EPCs) represent a heterogeneous cell population
      that is believed to be involved in vasculogenesis. With the purpose of enhancing
      endothelial repair, EPCs could have a potential for future cell therapies. Due to
      the low amount of EPCs in the peripheral circulating blood, in vitro expansion is
      needed before administration to recipients and the effects of in vitro culturing
      is still an under-evaluated field with little knowledge of how the cells change
      over time in culture. The aim of this study was to use hyperpolarised carbon-13
      magnetic resonance spectroscopy to profile important metabolic pathways in a
      population of progenitor cells and to show that cell culturing in 3D scaffolds
      seem to block the metabolic processes that leads to cell senescence. The
      metabolic breakdown of hyperpolarized [1-13C]pyruvate was followed after
      injection of the substrate to a bioreactor system with EPCs either adhered to 3D
      printed scaffolds or kept in cell suspension. The pyruvate-to-lactate conversion
      was elevated in suspension of EPCs compared to the EPCs adhered to scaffolds.
      Furthermore in the setup with EPCs in suspension, an increase in lactate
      production was seen over time indicating that the older the cultures of EPCs was
      before using the cells for cell suspension experiments, the more lactate they
      produce, compared to a constant lactate level in the cells adhered to scaffolds.
      It could therefore be stated that cells grown first in 2D culture and subsequent
      prepared for cell suspension show a metabolism with higher lactate production
      consistent with cells senescence processes compared to cells grown first at 2D
      culture and subsequent in the 3D printed scaffolds, where metabolism shows no
      sign of metabolic shifting during the monitored period.

PMID- 27720670
TI  - Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the
      airway smooth muscle cell in rat.
AB  - A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a
      susceptibility gene for asthma, but details of the causality are not fully
      understood. We hypothesize that soluble ADAM33 (sADAM33) overexpression can alter
      the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of
      the cell's contractile phenotype, and thus contributes to airway
      hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either
      overexpressed or knocked down the sADAM33 in rat ASMCs by transfecting the cells
      with sADAM33 coding sequence or a small interfering RNA (siRNA) that specifically
      targets the ADAM33 disintegrin domain, and subsequently assessed the cells for
      stiffness, contractility and traction force, together with the expression level
      of contractile and proliferative phenotype markers. We also investigated whether
      these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in
      the absence or presence of ROCK inhibitor (H1152). The results showed that the
      ASMCs with sADAM33 overexpression were stiffer and more contractile, generated
      greater traction force, exhibited increased expression levels of contractile
      phenotype markers and markedly enhanced Rho activation. Furthermore these changes
      were largely attenuated when the cells were cultured in the presence of H-1152.
      However, the knock-down of ADAM33 seemed insufficient to influence majority of
      the mechanical behaviors of the ASMCs. Taken together, we demonstrated that
      sADAM33 overexpression altered the mechanical behaviors of ASMCs in vitro, which
      was most likely by promoting a hypercontractile phenotype transition of ASMCs
      through Rho/ROCK pathway. This revelation may establish the previously missing
      link between ADAM33 expression and AHR, and also provide useful insight for
      targeting sADAM33 in asthma prevention and therapy.

PMID- 27720671
TI  - Genotoxic and cytotoxic effects of the environmental pollutant 3
      nitrobenzanthrone on bladder cancer cells.
AB  - 3-Nitrobenzanthrone (3-NBA), a potential human carcinogen, is present in diesel
      exhaust. The main metabolite of 3-NBA, 3-aminobenzanthrone, was detected in urine
      of miners occupationally exposed to diesel emissions. Environmental and
      occupational factors play an important role in development of bladder cancer
      (BC), one of the most frequent malignancies. It is expected that exposure of
      urothelium to 3-NBA and its metabolites may induce BC initiation and/or
      progression. To test this hypothesis, we studied geno- and cytotoxicity of 3-NBA
      using an in vitro BC model. 3-NBA induced higher levels of DNA adducts, reactive
      oxygen species and DNA breaks in aggressive T24 cells than in more differentiated
      RT4 cells. To understand the nature of this difference we examined the role of
      several enzymes that were identified as 3-NBA bio activators. However, the
      difference in DNA adduct formation cannot be directly linked to the different
      activity of any of the examined enzymes. Conversely, the difference of tested
      cell lines in p53 status can partly explain the distinct levels of 3-NBA-DNA
      adducts and DNA damage induced by 3-NBA. Therefore, we assume that more
      aggressive T24 cells are more predisposed for DNA adduct formation, DNA damage
      and, possibly, mutations and as a result further tumorigenesis.

PMID- 27720673
TI  - 58th ASTRO annual meeting.

PMID- 27720672
TI  - High expression of mitochondrial intermembrane chaperone TIMM9 represents a
      negative prognostic marker in gastric cancer.
AB  - BACKGROUND/PURPOSE: Gastric cancer (GC) is one of the most common malignant
      cancers worldwide. However, little is known about the molecular process
      underlying this disease and its progression. This study investigated correlations
      between the expression of a mitochondrial inner membrane protein translocase of
      inner mitochondrial membrane 9 homolog (TIMM9) and various clinicopathologic
      parameters as well as patients' survival. METHODS: Gastric tissue samples were
      obtained from 140 patients with GC and expression levels of TIMM9 were analyzed
      through immunohistochemistry. Paired t tests were used to analyze the differences
      in the expression levels of TIMM9 in both tumor and nontumor tissues for each
      patient. Two-tailed chi2 tests were performed to determine whether the
      differences in TIMM9 expression and clinicopathologic parameters were
      significant. Time-to-event endpoints for clinicopathologic parameters were
      plotted using the Kaplan-Meier method, and statistical significance was
      determined using univariate log-rank tests. Cox proportional hazard model was
      used for multivariate analysis to determine the independence of prognostic
      effects of TIMM9 expression. RESULTS: A borderline association was found between
      overexpression of TIMM9 and vascular invasion (p = 0.0887). Patients with high
      expression levels of TIMM9 achieved a significantly lower disease-free survival
      rate compared with those with low expression levels (p = 0.005). Multivariate Cox
      regression analysis showed that overexpression of TIMM9 was an independent
      prognostic marker for GC (p = 0.011). CONCLUSION: Overexpression of TIMM9 can be
      used as a marker to predict the outcome of patients with GC.

PMID- 27720674
TI  - No increase in childhood leukaemia near UK nuclear sites.

PMID- 27720675
TI  - Cultivable Methylobacterium species diversity in rice seeds identified with whole
      cell matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometric analysis.
AB  - Methylobacterium species are methylotrophic bacteria that widely inhabit plant
      surfaces. In addition to studies on methylotrophs as model organisms, research
      has also been conducted on their mechanism of plant growth promotion as well as
      the species-species specificity of plant-microbe interaction. We employed whole
      cell matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (WC
      MS) analysis, which enables the rapid and accurate identification of bacteria at
      the species level, to identify Methylobacterium isolates collected from the rice
      seeds of different cultivars harvested in Japan, Thailand, and Kenya. Rice seeds
      obtained from diverse geographical locations showed different communities of
      Methylobacterium species. We found that M. fujisawaense, M. aquaticum, M.
      platani, and M. radiotolerans are the most frequently isolated species, but none
      were isolated as common species from 18 seed samples due to the highly biased
      communities in some samples. These findings will contribute to the development of
      formulations containing selected species that promote rice growth, though it may
      be necessary to customize the formulations depending on the cultivars and farm
      conditions.

PMID- 27720676
TI  - The Assembly Pathway of Mitochondrial Respiratory Chain Complex I.
AB  - Mitochondrial complex I is the largest integral membrane enzyme of the
      respiratory chain and consists of 44 different subunits encoded in the
      mitochondrial and nuclear genome. Its biosynthesis is a highly complicated and
      multifaceted process involving at least 14 additional assembly factors. How these
      subunits assemble into a functional complex I and where the assembly factors come
      into play is largely unknown. Here, we applied a dynamic complexome profiling
      approach to elucidate the assembly of human mitochondrial complex I and its
      further incorporation into respiratory chain supercomplexes. We delineate the
      stepwise incorporation of all but one subunit into a series of distinct assembly
      intermediates and their association with known and putative assembly factors,
      which had not been implicated in this process before. The resulting detailed and
      comprehensive model of complex I assembly is fully consistent with recent
      structural data and the remarkable modular architecture of this multiprotein
      complex.

PMID- 27720678
TI  - A novel missense mutation of NDP in a Chinese family with X-linked familial
      exudative vitreoretinopathy.
AB  - Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder
      characterized by a failure of peripheral retinal vascularization. In this report,
      we describe a novel missense mutation of the Norrie disease gene (NDP) in a
      Chinese family with X-linked FEVR. Ophthalmologic evaluation was performed on
      four male patients and seven unaffected individuals after informed consent was
      obtained. Venous blood was collected from the 11 members of this family, and
      genomic DNA was extracted using standard methods. The coding exons 2 and 3 and
      their corresponding exon-intron junctions of NDP were amplified by polymerase
      chain reaction and then subjected to direct DNA sequencing. A novel missense
      mutation (c.310A>C) in exon 3, leading to a lysine-to-glutamine substitution at
      position 104 (p.Lys104Gln), was identified in all four patients with X-linked
      FEVR. Three unaffected female individuals (III2, IV3, and IV11) were found to be
      carriers of the mutation. This mutation was not detected in other unaffected
      individuals. The mutation c.310A>C (p.Lys104Gln) in exon 3 of NDP is associated
      with FEVR in the studied family. This result further enriches the mutation
      spectrum of FEVR.

PMID- 27720677
TI  - Phagocytosis of bone marrow derived macrophages is controlled by phosphoinositide
      3-kinase gamma.
AB  - Due to their ability to phagocytise invading microbes macrophages play a key role
      in the innate and acquired immune system. In this article the role of
      phosphoinositide 3-kinase gamma (PI3Kgamma) for phagocytosis was studied in bone
      marrow derived macrophages (BMDM). By using genetic and pharmacological
      approaches our data clearly demonstrate PI3Kgamma is acting as a mediator of
      macrophage phagocytosis. Phagocytosis of LPS activated BMDM was reduced in
      PI3Kgamma depleted primary BMDM or macrophage cell line J774. Depletion of other
      class I phosphoinositide 3-kinases did not alter phagocytic activity. Partial
      reduction of the phagocytic index of BMDM expressing kinase inactive PI3Kgamma
      indicate a lipid-kinase independent role of the PI3Kgamma protein. Since
      inhibition of PI3Kgamma interaction partner phosphodiesterase PDE3B reduced BMDM
      phagocytosis and PI3Kgamma knock out super stimulated cAMP level, our data reveal
      that PI3Kgamma protein mediated suppression of cAMP signalling is a critical for
      efficient phagocytosis of macrophages.

PMID- 27720679
TI  - Fetuin-A downregulates adiponectin through Wnt-PPARgamma pathway in lipid induced
      inflamed adipocyte.
AB  - Adiponectin secreted from adipocytes is an anti-diabetic and anti-atherogenic
      adipokine. Adiponectin level is known to fall significantly in obesity induced
      type 2 diabetes which worsen insulin sensitivity because of aberrant lipid
      management. However, underlying mechanism of adiponectin decrease in obese
      diabetic condition is yet unclear. We report here that lowering of plasma
      adiponectin coincided with the higher Fetuin A (FetA) level in high fat diet
      (HFD) induced obese diabetic mice. Knock down of FetA gene (FetAKD) elevated
      adiponectin level markedly in HFD mice, while reinforcement of FetA into
      FetAKDHFD mice reduced its level again. These results indicate FetA's involvement
      in the lowering of adiponectin level in obesity induced diabetic mice. Our
      findings to understand how FetA could affect adiponectin decrease demonstrated
      that FetA could enhance Wnt3a expression in the adipocyte of HFD mice. FetA
      addition to 3T3L1 adipocyte incubation elevated Wnt3a expression in a dose
      dependent manner. Overexpression of Wnt3a by FetA inhibited PPARgamma and
      adiponectin. FetA failed to reduce PPARgamma and adiponectin in Wnt3a gene
      knocked down 3T3L1' adipocytes. All these suggest that FetA mediate its
      inhibitory effect on adiponectin through Wnt3a-PPARgamma pathway. Inhibition of
      adiponectin expression through FetA and Wnt3a significantly compromised with the
      activation of AMPK and its downstream signalling molecules which adversely
      affected lipid management causing loss of insulin sensitivity. Downregulation of
      adiponectin in inflamed adipocyte by FetA through the mediation of Wnt3a and
      PPARgamma is a new report.

PMID- 27720680
TI  - High throughput solid phase microextraction: A new alternative for analysis of
      cellular lipidome?
AB  - A new SPME method for untargeted lipidomic study of cell line cultures was
      proposed for the first time. In this study the feasibility to monitor changes in
      lipid profile after external stimuli was demonstrated and compared to the
      conventional Bligh & Dyer method. The human hepatocellular carcinoma (HCC) cell
      line was used as a model. The obtained results provided a list of up-regulated
      and down-regulated lipids through a comparison between control (non-stimulated)
      cells versus the group of cells treated with polyunsaturated fatty acid (20:5).
      Use of the SPME technique yielded a list of 77 lipid species whose concentrations
      were recognized to be significantly different between control and treated cells,
      from which 63 lipids were up-regulated in treated cells. In general, the list was
      comparable to the peer list obtained by the Bligh & Dyer method. However, more
      diversity of lipid classes and subclasses such as LPC, sphingomyelins, ceramides,
      and prenol lipids were observed with the application of the SPME method. Method
      precision for the SPME approach was within the acceptable analytical range (5-18%
      RSD) for all detected lipids, which was advantageous over solvent extraction
      applied. The evaluation of ionization efficiency indicated no matrix effect for
      the SPME technique, while Bligh & Dyer presented significant ionization
      suppression for low abundant species such as LysoPC, PG, ceramides, and
      sphingomyelins, and ionization enhancement for high abundant phospholipids such
      as PE.

PMID- 27720681
TI  - Palmitoylethanolamide reduces inflammation and itch in a mouse model of contact
      allergic dermatitis.
AB  - In mice, 2,4-dinitrofluorobenzene (DNFB) induces contact allergic dermatitis
      (CAD), which, in a late phase, is characterized by mast cell (MC) infiltration
      and angiogenesis. Palmitoylethanolamide (PEA), an endogenous anti-inflammatory
      molecule, acts by down-modulating MCs following activation of the cannabinoid CB2
      receptor and peroxisome proliferator-activated receptor-alpha (PPAR-alpha). We
      have previously reported the anti-inflammatory effect of PEA in the early stage
      of CAD. Here, we examined whether PEA reduces the features of the late stage of
      CAD including MC activation, angiogenesis and itching. After sensitization to
      DNFB, female C57BL/6J mice underwent to three DNFB challenges at days 5, 12 and
      19 and treatments were given at each challenge and for two more days. CAD was
      expressed as Delta increase in ear thickness between challenged and un-challenged
      mice. PEA (5mg/kg/i.p.) reduced: i) the DNFB-induced Delta increase; ii) the
      number of MCs per tissue area; iii) the expression of VEGF and its receptor Flk
      1. These effects were reversed by co-administration of AM630 (1mg/kg/i.p.), a CB2
      antagonist, but not GW6471 (1mg/kg/i.p.), a PPAR-alpha antagonist. Finally, PEA
      reduced the number of ear scratchings 48h after DNFB challenge and this effect
      was reversed by both CB2 and PPAR-alpha antagonists, suggesting the involvement
      of both receptors. PEA, by reducing the features of late stage CAD in mice, may
      be beneficial in this pathological condition.

PMID- 27720682
TI  - Updated mitochondrial phylogeny of Pteriomorph and Heterodont Bivalvia, including
      deep-sea chemosymbiotic Bathymodiolus mussels, vesicomyid clams and the thyasirid
      clam Conchocele cf. bisecta.
AB  - The mitochondrial genomes of bivalves have often been used for comparative
      genomics and for resolving phylogenetic relationships. More than 100 bivalve
      complete mitochondrial genomes have been sequenced to date. However, few
      mitochondrial genomes have been reported for deep-sea chemosymbiotic bivalves,
      which belong to the subclasses Pteriomorphia and Heterodonta. In the present
      study, we sequenced the mitochondrial genomes of eight deep-sea chemosymbiotic
      bivalve species: three species of Bathymodiolus mussels (B. japonicus, B.
      platifrons, and B. septemdierum), four species of vesicomyid clams (Abyssogena
      mariana, A. phaseoliformis, Isorropodon fossajaponicum, and Phreagena okutanii,
      all of which were formerly classified in the genus Calyptogena), and one species
      of thyasirid clam (Conchocele cf. bisecta). With a few exceptions, these
      mitochondrial genomes contained genes that are typical of metazoans: 13 protein
      coding genes, two rRNA genes, and 22 tRNA genes. The major non-coding region with
      a high A+T content of each genome, which contained tandem repeats and hairpins,
      was hypothesized to function as a control region. The phylogenetic trees of
      Pteriomorphia and Heterodonta were reconstructed based on the concatenated
      sequences of 14 shared genes. Bathymodiolus formed a monophyletic clade with
      asymbiotic Mytilidae mussels, the vesicomyid clams formed a monophyly that was
      sister to the Veneridae, and C. cf. bisecta branched basally in the Heterodonta.
      It is known that the gene orders of mitochondrial genomes vary among bivalves. To
      examine whether gene order variation exhibits phylogenetic signals, tree
      topologies based on the minimum number of gene rearrangements were reconstructed
      for two clades (superfamily Tellinoidea, which includes the Psammobiidae,
      Semelidae, Solecurtidae, and Tellinidae; and the clade comprising the Myidae,
      Mactridae, Arcticidae, Vesicomyidae, and Veneridae) with high statistical support
      in sequence-based phylogenies. The resulting tree topologies were almost
      identical to those of the sequence-based trees. Our present findings suggest that
      the evolution of bivalves could be precisely traced back through the analysis of
      mitochondrial genomes, and that such an analysis could contribute to
      understanding bivalve evolution and diversity.

PMID- 27720683
TI  - The role of face transplantation in the self-inflicted gunshot wound.
AB  - BACKGROUND: Facial self-inflicted gunshot wounds (SIGSWs) cause a devastating
      midfacial defect and pose a challenging problem to the reconstructive surgeon.
      Face transplantation (FT) has the potential for near-normal restoration in
      otherwise non-reconstructible defects. Two out of 7 FT recipients at Brigham and
      Women's Hospital (BWH) sustained SIGSWs. In this study, we illustrate the role of
      FT in the management of SIGSWs through an aesthetic, functional, and psychosocial
      examination of outcomes. METHODS: We performed a retrospective analysis of
      individuals with SIGSWs who were screened at BWH between 2008 and 2015. We then
      collected data of the injuries, modes of conventional reconstruction (CR), and
      deficits. For the FT recipients, we critically reviewed the psychosocial
      screening process and post-transplantation aesthetic, functional, and
      psychosocial outcomes. RESULTS: A total of six individuals post-SIGSWs were
      screened for FT. All of them had undergone CR, with five receiving loco-regional
      flaps and free tissue transfers, and one undergoing serial debridement and
      primary soft-tissue repair. Following CR, all suffered from residual functional
      and aesthetic deficits. Two underwent partial FT and one is currently undergoing
      FT screening. We describe the pre-transplant psychosocial screening process and
      the aesthetic, functional, and psychosocial outcomes of the SIGSW FT recipients.
      CONCLUSIONS: We examined the facial SIGSW injury, outcomes of CR, and the
      mechanism of FT to offer a potential solution to the shortcomings of CR. More
      importantly, we highlight the critical nature of the psychosocial component of
      the multidisciplinary evaluation given the history of mental illness and suicidal
      behavior in this subset of patients.

PMID- 27720684
TI  - Anti-inflammatory signaling actions of electrophilic nitro-arachidonic acid in
      vascular cells and astrocytes.
AB  - Nitrated derivatives of unsaturated fatty acids (nitro-fatty acids) are being
      formed and detected in human plasma, cell membranes and tissue, triggering
      signaling cascades via covalent and reversible post-translational modifications
      of nucleophilic amino acids in transcriptional regulatory proteins. Arachidonic
      acid (AA) represents a precursor of potent signaling molecules, i.e.,
      prostaglandins and thromboxanes through enzymatic and non-enzymatic oxidative
      pathways. Arachidonic acid can be nitrated by reactive nitrogen species leading
      to the formation of nitro-arachidonic acid (NO2-AA). A critical issue is the
      influence of NO2-AA on prostaglandin endoperoxide H synthases, modulating
      inflammatory processes through redirection of AA metabolism and signaling. In
      this prospective article, we describe the key chemical and biochemical actions of
      NO2-AA in vascular and astrocytes. This includes the ability of NO2-AA to mediate
      unique redox signaling anti-inflammatory actions along with its therapeutic
      potential.

PMID- 27720685
TI  - Insight into the impact of two structural calcium ions on the properties of
      Pleurotus eryngii versatile ligninolytic peroxidase.
AB  - Two structural Ca2+ (proximal and distal) is known to be important for
      ligninolytic peroxidases. However, few studies toward impact of residues involved
      in two Ca2+ on properties of ligninolytic peroxidases have been done, especially
      the proximal one. In this study, mutants of nine residues involved in liganding
      two Ca2+ of Pleurotus eryngii versatile peroxidase (VP) were investigated. Most
      mutants almost completely lost activities, except the mutants of proximal Ca2+ -
      S170A and V192T. In comparison with WT (wild type), optimal pH values of S170A,
      S170D, and V192T shifted from pH 3.0 to pH 3.5. The order of thermal and pH
      stabilities of WT, V192T, S170A, and S170D is similar to that of their specific
      activities: WT > V192T > S170A > S170D. The CD (circular dichroism) results of WT
      and several mutants indicated that mutations had some effects on secondary
      structures. For the first time, it was observed that the thermostability of
      ligninolytic peroxidases is related with proximal Ca2+ too, and the mutant
      containing distal Ca2+ only was obtained. Our results clearly demonstrated that
      enzymatic activities, pH and thermal stabilities, Ca2+content, and secondary
      structures of VP have close relationship with the residues involved in two
      structural Ca2+.

PMID- 27720686
TI  - Role of pannexin 1 in Clostridium perfringens beta-toxin-caused cell death.
AB  - BACKGROUND: Beta-toxin produced by Clostridium perfringens is a key virulence
      factor of fatal hemorrhagic enterocolitis and enterotoxemia. This toxin belongs
      to a family of beta-pore-forming toxins (PFTs). We reported recently that the ATP
      gated P2X7 receptor interacts with beta-toxin. The ATP-release channel pannexin 1
      (Panx1) is an important contributor to P2X7 receptor signaling. Hence, we
      investigated the involvement of Panx1 in beta-toxin-caused cell death. METHODS:
      We examined the effect of Panx1 in beta-toxin-induced cell death utilizing
      selective antagonists, knockdown of Panx1, and binding using dot-blot analysis.
      Localization of Panx1 and the P2X7 receptor after toxin treatment was determined
      by immunofluorescence staining. RESULTS: Selective Panx1 antagonists
      (carbenoxolone [CBX], probenecid, and Panx1 inhibitory peptide) prevented beta
      toxin-caused cell death in THP-1 cells. CBX did not block the binding of the
      toxin to cells. Small interfering knockdown of Panx1 blocked beta-toxin-mediated
      cell death through inhibiting the oligomer formation of the toxin. Beta-toxin
      triggered a transient ATP release from THP-1 cells, but this early ATP release
      was blocked by CBX. ATP scavengers (apyrase and hexokinase) inhibited beta-toxin
      induced cytotoxicity. Furthermore, co-administration of ATP with beta-toxin
      enhanced the binding and cytotoxicity of the toxin. CONCLUSIONS: Based on our
      results, Panx1 activation is achieved through the interaction of beta-toxin with
      the P2X7 receptor. Then, ATP released by the Panx1 channel opening promotes
      oligomer formation of the toxin, leading to cell death. GENERAL SIGNIFICANCE:
      Pannexin 1 is a novel candidate therapeutic target for beta-toxin-mediated
      disease.

PMID- 27720687
TI  - Putting numbers on the End TB Strategy-an impossible dream?

PMID- 27720691
TI  - Acute Myeloid Leukemia Presenting with Sweet Syndrome: A Case Report and Review
      of the Literature.

PMID- 27720690
TI  - Aluminum trichloride induces bone impairment through TGF-beta1/Smad signaling
      pathway.
AB  - Aluminum (Al) is recognized worldwide as serious inorganic contaminants. Exposure
      to Al is associated with low BMD and an increased risk of osteoporosis. However,
      the precise molecular mechanisms remains unclear. Thus, in this study, rats were
      orally exposed to 0 (control group, CG) and 0.4g/L AlCl3 (AlCl3 treated group,
      AG) in drinking water for 120days; osteoblasts were treated with AlCl3
      (0.12mg/mL) and/or TGF-beta1 (4.5ng/mL) for 24h. We found that AlCl3 decreased
      the BMD, damaged femoral ultrastructure, decreased the activities of GSH-Px and
      SOD, and increased the levels of ROS and MDA in bone, decreased the activity of B
      ALP and content of PINP, and increased the activity of TRACP-5b and content of
      NTX-I in serum, decreased mRNA expressions of TGF-beta1, TbetaRI, TbetaRII and
      Smad4, protein expressions of TGF-beta1, p-Smad2/3 and Smad2/3/4 complex, and
      increased Smad7 mRNA expression in bone and in osteoblasts. Moreover, we found
      exogenous TGF-beta1 application reversed the inhibitory effect of AlCl3 on
      osteoblasts activity by activating the TGF-beta1/Smad signaling pathway and
      increasing the mRNA expressions of ALP and Col I in osteoblasts. These results
      demonstrate that AlCl3 induces bone impairment through inactivation of TGF
      beta1/Smad signaling pathway.

PMID- 27720688
TI  - Feasibility of achieving the 2025 WHO global tuberculosis targets in South
      Africa, China, and India: a combined analysis of 11 mathematical models.
AB  - BACKGROUND: The post-2015 End TB Strategy proposes targets of 50% reduction in
      tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025.
      We aimed to assess whether these targets are feasible in three high-burden
      countries with contrasting epidemiology and previous programmatic achievements.
      METHODS: 11 independently developed mathematical models of tuberculosis
      transmission projected the epidemiological impact of currently available
      tuberculosis interventions for prevention, diagnosis, and treatment in China,
      India, and South Africa. Models were calibrated with data on tuberculosis
      incidence and mortality in 2012. Representatives from national tuberculosis
      programmes and the advocacy community provided distinct country-specific
      intervention scenarios, which included screening for symptoms, active case
      finding, and preventive therapy. FINDINGS: Aggressive scale-up of any single
      intervention scenario could not achieve the post-2015 End TB Strategy targets in
      any country. However, the models projected that, in the South Africa national
      tuberculosis programme scenario, a combination of continuous isoniazid preventive
      therapy for individuals on antiretroviral therapy, expanded facility-based
      screening for symptoms of tuberculosis at health centres, and improved
      tuberculosis care could achieve a 55% reduction in incidence (range 31-62%) and a
      72% reduction in mortality (range 64-82%) compared with 2015 levels. For India,
      and particularly for China, full scale-up of all interventions in tuberculosis
      programme performance fell short of the 2025 targets, despite preventing a
      cumulative 3.4 million cases. The advocacy scenarios illustrated the high impact
      of detecting and treating latent tuberculosis. INTERPRETATION: Major reductions
      in tuberculosis burden seem possible with current interventions. However,
      additional interventions, adapted to country-specific tuberculosis epidemiology
      and health systems, are needed to reach the post-2015 End TB Strategy targets at
      country level. FUNDING: Bill and Melinda Gates Foundation.

PMID- 27720692
TI  - Modelling late stool frequency and rectal pain after radical radiotherapy in
      prostate cancer patients: Results from a large pooled population.
AB  - AIM: To investigate late gastrointestinal toxicity in a large pooled population
      of prostate cancer patients treated with radical radiotherapy. Normal tissue
      complication probability models were developed for late stool frequency and late
      rectal pain. METHODS AND MATERIALS: Population included 1336 patients, 3-year
      minimum follow-up, treated with 66-80Gy. Toxicity was scored with LENT-SOMA
      scale. Two toxicity endpoints were considered: grade ?2 rectal pain and mean
      grade (average score during follow-up) in stool frequency >1. DVHs of anorectum
      were reduced to equivalent uniform dose (EUD). The best-value of the volume
      parameter n was determined through numerical optimization. Association between
      EUD/clinical factors and the endpoints was investigated by logistic analyses.
      Likelihood, Brier-score and calibration were used to evaluate models. External
      calibration was also carried out. RESULTS: 4% of patients (45/1122) reported mean
      stool frequency grade >1; grade ?2 rectal pain was present in the TROG 03.04
      RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited
      to this population. Analysis of DVHs highlighted the importance of mid-range
      doses (30-50Gy) for both endpoints. EUDs calculated with n=1 (OR=1.04) and n=0.35
      (OR=1.06) were the most suitable dosimetric descriptors for stool frequency and
      rectal pain respectively. The final models included EUD and cardiovascular
      diseases (OR=1.78) for stool frequency and EUD and presence of acute
      gastrointestinal toxicity (OR=4.2) for rectal pain. CONCLUSION: Best predictors
      of stool frequency and rectal pain are consistent with findings previously
      reported for late faecal incontinence, indicating an important role in
      optimization of mid-range dose region to minimize these symptoms highly impacting
      the quality-of-life of long surviving patients.

PMID- 27720694
TI  - The power of capturing and using information at the point of care.
AB  - Historically, the process of scientific discovery and the process of clinical
      delivery have been poorly integrated. As a result of the Decade of Health
      Information Technology (2004-2014), many of the former barriers to capturing,
      processing, and retrieving medical information at the point of care have been
      surmounted. This change has the potential to both transform how new medical
      discoveries are made and how evidence-based medicine is put into practice. To
      illustrate the impact of this ongoing change, several examples are provided of
      institutions which have innovatively used information at the point of care.

PMID- 27720693
TI  - Ethnic and sex-specific cut-off values for adult obesity in the Suriname Health
      Study.
AB  - BACKGROUND: Sex-specific body mass index (BMI) and waist circumference (WC) cut
      off values have been validated for a limited number of ethnic groups. We aimed to
      derive these cut-off values for Amerindians, Creoles, Hindustani, Javanese,
      Maroons and Mixed living in Suriname. METHODS: Data from individuals aged 20-65,
      in the Suriname Health Study was used to derive optimal cut-off values for BMI
      and WC for the prediction of hypertension (n=4910) and cardio-metabolic risk
      (n=2924). Results from the analysis with Receiver Operating Curves were
      calculated and compared these with recommended values. RESULTS: The area under
      the ROC curve was consistently higher for WC compared to BMI among Creoles,
      Hindustani, Maroons and Mixed. The BMI cut-off values ranged from 24.8kg/m2 for
      Creole men and 26.9kg/m2 for Maroon women to 28.4kg/m2 and 30.2kg/m2 for
      Amerindian men and women, respectively. The WC cut-off values ranged from 80.7cm
      for Maroon men, 86.7cm for Javanese women to 90.8cm for Hindustani men and 95.7cm
      for Amerindian women. Optimal BMI cut-off values approximated Asian cut-off
      values from the World Health Organization whilst those of WC for men approximated
      and for women exceeded cut-off values from the International Diabetes Federation.
      CONCLUSION: In most ethnic groups, we found better discriminatory power for WC
      compared to BMI in the relation with cardiovascular risk factors. The estimated
      BMI and WC cut-off values differed between ethnic groups. Further studies are
      needed to identify cut-off values related to the future risk of cardiovascular
      disease and mortality.

PMID- 27720696
TI  - Transcriptome analysis of grey mullet (Mugil cephalus) after challenge with
      Lactococcus garvieae.
AB  - Grey mullet (Mugil cephalus) is an economically important fish species in Taiwan
      mariculture industry. Moreover, grey mullet are common hosts of a bacterial
      infection by Lactococcus garvieae. However, until now the information related to
      the immune system of grey mullet is unclear. Therefore, to understand the
      molecular basis underlying the host immune response to L. garvieae infection,
      Illumina HiSeqTM 2000 was used to analyse the head kidney and spleen
      transcriptome of infected grey mullet. De novo assembly of paired-end reads
      yielded 55,203 unigenes. Comparative analysis of the expression profiles between
      bacterial challenge fish and control fish identified a total of 7192 from head
      kidney and 7280 in spleen differentially expressed genes (P < 0.05), including
      4211 upregulated genes and 2981 downregulated genes in head kidney, while in
      spleen 3598 genes were upregulated and 3682 downregulated. A significant
      enrichment analysis of these differentially expressed genes (DEG) in spleen and
      head kidney revealed major immune-related pathways, including complement and
      coagulation cascades, Toll-like receptor signalling, and antigen processing and
      presentation. Moreover, selected DEGs were validated using qPCR. Altogether, the
      results obtained on immune-related genes may allow for a better understanding of
      immunity in grey mullet to Lactococcus garvieae, carrying out detailed functional
      analysis of these genes and developing strategies for efficient immune protection
      against infections in grey mullet.

PMID- 27720695
TI  - CD94 of tongue sole Cynoglossus semilaevis binds a wide arrange of bacteria and
      possesses antibacterial activity.
AB  - In this study, we examined the expression patterns and the functions of the
      tongue sole Cynoglossus semilaevis CD94, CsCD94. CsCD94 is composed of 209 amino
      acid residues and shares 43.0-50.2% overall identities with known teleost CD94
      sequence. CsCD94 has a C-type lectin-like domain. Expression of CsCD94 occurred
      in multiple tissues and was upregulated during bacterial infection. Recombinant
      CsCD94 (rCsCD94) exhibited apparent binding and agglutinating activities against
      both Gram-positive and Gram-negative bacteria in a Ca2+-dependent manner.
      Treatment of bacteria with rCsCD94 enhanced phagocytosis of the bacteria by
      peripheral blood leukocytes. Furthermore, incubation of rCsCD94 with bacteria
      reduced the survival of the bacteria in vitro. Taken together, these results
      indicate that rCsCD94 is a key factor in the bactericidal and phagocytic effects
      of tongue sole, and reveal for the first time an essential role of fish CD94 in
      antibacterial immunity, thereby adding insight into the function of CD94.

PMID- 27720697
TI  - Alpha 1-antitrypsin levels can differentiate allelic phenotypes.

PMID- 27720689
TI  - Cost-effectiveness and resource implications of aggressive action on tuberculosis
      in China, India, and South Africa: a combined analysis of nine models.
AB  - BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing
      tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess
      resource requirements and cost-effectiveness of strategies to achieve these
      targets in China, India, and South Africa. METHODS: We examined intervention
      scenarios developed in consultation with country stakeholders, which scaled up
      existing interventions to high but feasible coverage by 2025. Nine independent
      modelling groups collaborated to estimate policy outcomes, and we estimated the
      cost of each scenario by synthesising service use estimates, empirical cost data,
      and expert opinion on implementation strategies. We estimated health effects (ie,
      disability-adjusted life-years averted) and resource implications for 2016-35,
      including patient-incurred costs. To assess resource requirements and cost
      effectiveness, we compared scenarios with a base case representing continued
      current practice. FINDINGS: Incremental tuberculosis service costs differed by
      scenario and country, and in some cases they more than doubled existing funding
      needs. In general, expansion of tuberculosis services substantially reduced
      patient-incurred costs and, in India and China, produced net cost savings for
      most interventions under a societal perspective. In all three countries,
      expansion of access to care produced substantial health gains. Compared with
      current practice and conventional cost-effectiveness thresholds, most
      intervention approaches seemed highly cost-effective. INTERPRETATION: Expansion
      of tuberculosis services seems cost-effective for high-burden countries and could
      generate substantial health and economic benefits for patients, although
      substantial new funding would be required. Further work to determine the optimal
      intervention mix for each country is necessary. FUNDING: Bill & Melinda Gates
      Foundation.

PMID- 27720698
TI  - Spontaneous passage of a large common bile duct stone during computed tomography.

PMID- 27720699
TI  - A 15-year experience of two hundred and twenty five consecutive right
      hepatectomies.
AB  - BACKGROUND: In case of liver tumor, surgical resection is the therapeutic gold
      standard to increase patient survival. Among liver resections, right hepatectomy
      (RH) is defined as a major hepatectomy. The first aim of this study was to
      analyze the overall morbidity and mortality of patients undergoing RH, the second
      aim was to assess changes in both patients characteristic and surgical parameters
      and mortality rates in a single center institution. MATERIALS: From 2001 to
      December 2015, 225 RH were performed in our center. We analyzed two time period:
      2001-2007 and 2008-2015. RESULTS: Ninety days post operative mortality was
      observed in 9 cases (4%) for the overall cohort. We observed a difference between
      the two groups in the use of Pringle Maneuver (p<0,001). This result is
      consistent in each major surgical indication: HCC (p=0,001), CLM (p=0,015) and BT
      (p=0,015). The estimated blood losses improved (p=0,028), particularly for the
      HCC cases (p=0,024). No difference was observed in terms of number of
      transfusions received between the two groups. Reduced length of stay was observed
      in the second group (p<0,001), more markedly for CLM cases (p=0,001). CONCLUSION:
      To further improve the outcomes of RH, it is important to performed this major
      hepatectomy in hepatobiliary centers with an overall liver resection experience
      of at least few hundred cases.

PMID- 27720700
TI  - Manometric evaluation of anorectal function in patients treated with neoadjuvant
      chemoradiotherapy and total mesorectal excision for rectal cancer.
AB  - BACKGROUND: An altered anorectal function is reported after chemoradiotherapy
      (CRT) and surgery for rectal cancer. AIM: The aim of this study was to clarify
      the relative contribution of neoadjuvant chemoradiation and surgical resection on
      the impairment of anorectal function as evaluated by anorectal manometry.
      METHODS: Thirty-nine patients with rectal cancer, who underwent neoadjuvant CRT
      and laparoscopic rectal resection, were evaluated with the Pescatori Faecal
      Incontinence score, and with anorectal manometry: before neoadjuvant therapy
      (T0), after neoadjuvant therapy and before surgery (T1), 12 months after stoma
      closure (T2). RESULTS: Resting and/or maximum squeeze pressure and/or volume
      thresholds for urgency were below the normal values in 12 (30%) patients at
      baseline. After CRT the mean resting pressure significantly decreased (p=0.007).
      Surgery determined a significantly decrease of the resting pressure (p=0.001), of
      the maximum squeeze pressure (p=0.001) and of the volume threshold for urgency
      (p=0.001). Impairment of continence was reported by 5, 11 and 18 patients at T0,
      T1 and T2, with a mean incontinence score of 3, 3.8 and 3.9 respectively.
      CONCLUSIONS: CRT is detrimental to the function of the internal anal sphincter.
      Rectal resection significantly affects both internal and external anal sphincter
      function and the maximum tolerated volume of the neo-rectum, particularly in
      patients with low rectal cancer, significantly impairing anal continence.

PMID- 27720701
TI  - Detailed prospective peer review in a community radiation oncology clinic.
AB  - PURPOSE: In 2012, we instituted detailed prospective peer review of new cases. We
      present the outcomes of peer review on patient management and time required for
      peer review. METHODS AND MATERIALS: Peer review rounds were held 3 to 4 days
      weekly and required 2 physicians to review pertinent information from the
      electronic medical record and treatment planning system. Eight aspects were
      reviewed for each case: 1) workup and staging; 2) treatment intent and
      prescription; 3) position, immobilization, and simulation; 4) motion assessment
      and management; 5) target contours; 6) normal tissue contours; 7) target
      dosimetry; and 8) normal tissue dosimetry. Cases were marked as, "Meets standard
      of care," "Variation," or "Major deviation." Changes in treatment plan were
      noted. As our process evolved, we recorded the time spent reviewing each case.
      RESULTS: From 2012 to 2014, we collected peer review data on 442 of 465 (95%)
      radiation therapy patients treated in our hospital-based clinic. Overall, 91
      (20.6%) of the cases were marked as having a variation, and 3 (0.7%) as major
      deviation. Forty-two (9.5%) of the cases were altered after peer review. An
      overall peer review score of "Variation" or "Major deviation" was highly
      associated with a change in treatment plan (P < .01). Changes in target contours
      were recommended in 10% of cases. Gastrointestinal cases were significantly
      associated with a change in treatment plan after peer review. Indicators on
      position, immobilization, simulation, target contours, target dosimetry, motion
      management, normal tissue contours, and normal tissue dosimetry were
      significantly associated with a change in treatment plan. The mean time spent on
      each case was 7 minutes. CONCLUSIONS: Prospective peer review is feasible in a
      community radiation oncology practice. Our process led to changes in 9.5% of
      cases. Peer review should focus on technical factors such as target contours and
      dosimetry. Peer review required 7 minutes per case.

PMID- 27720702
TI  - Preoperative short-course radiation therapy for rectal cancer provides excellent
      disease control and toxicity: Results from a single US institution.
AB  - PURPOSE: Preoperative short-course radiation therapy (SCRT) has rarely been used
      for rectal cancer in the United States, although 2 randomized phase 3 trials
      demonstrate equivalence to conventional chemoradiation (CRT), and recent updates
      to national guidelines include this regimen as a treatment option. We sought to
      evaluate the efficacy and safety of preoperative SCRT followed by immediate
      surgery within 1 week to treat rectal cancer in the US setting. METHODS AND
      MATERIALS: All patients treated with preoperative SCRT (4 Gy * 5 fractions for
      total 20 Gy) followed by planned surgery within 1 week at our institution were
      retrospectively evaluated. Censored cases with >=2 years of follow-up were
      included along with any disease failure or death. Patients with cM1 disease were
      excluded. Patients with yp stage II/III disease typically received adjuvant
      chemotherapy from the 1990s onwards. The primary outcomes were actuarial (Kaplan
      Meier) 5-year locoregional control (LC), disease-free survival (DFS), and overall
      survival (OS) as well as late severe (greater than or equal to grade 3) toxicity.
      RESULTS: Our analysis included 202 consecutive patients with clinical stage I-III
      disease treated from 1977 through 2011. Median follow-up was 6.5 years (range, 2
      29.2). Five-year disease outcomes were 95.9% +/- 1.5% for LC, 76.4% +/- 3.1% for
      DFS, and 84.6% +/- 2.6% for OS. For patients with locally advanced rectal cancer
      (cT3-4 and/or cN+), 5-year LC, DFS, and OS were 95.1% +/- 2.1%, 73.3% +/- 4.3%,
      and 80.6% +/- 3.7%, respectively. The late severe toxicity rate was 11.4%.
      CONCLUSIONS: SCRT followed by immediate surgery is a safe and effective treatment
      for patients with rectal cancer in the United States. Though SCRT has not been
      widely adopted, recent updates to the national guidelines for rectal cancer as
      well as financial pressures to reduce healthcare costs may lead to increased
      utilization of this treatment regimen in the future.

PMID- 27720703
TI  - Margin of error for a frameless image guided radiosurgery system: Direct
      confirmation based on posttreatment MRI scans.
AB  - PURPOSE: To report on radiosurgery delivery positioning accuracy in the treatment
      of tremor patients with frameless image guided radiosurgery using the linear
      accelerator (LINAC) based ExacTrac system and to describe quality assurance (QA)
      procedures used. METHODS AND MATERIALS: Between 2010 and 2015, 20 patients
      underwent radiosurgical thalamotomy targeting the ventral intermediate nucleus
      for the treatment of severe tremor. The median prescription dose was 140 Gy
      (range, 120-145 Gy) in a single fraction. The median maximum dose was 156 Gy
      (range, 136-162 Gy). All treatment planning was performed with the iPlan system
      using a 4-mm circular cone with multiple arcs. Before each treatment, QA
      procedures were performed, including the imaging system. As a result of the
      extremely high dose delivered in a single fraction, a well-defined circular mark
      developed on the posttreatment magnetic resonance imaging (MRI). Eight of these
      20 patients were selected to evaluate treatment localization errors because their
      circular marks were available in posttreatment MRI. In this study, the
      localization error is defined as the distance between the center of the intended
      target and the center of the posttreatment mark. RESULTS: The mean error of
      distance was found to be 1.1 mm (range, 0.4-1.5 mm). The mean errors for the left
      right, anteroposterior, and superoinferior directions are 0.5 mm, 0.6 mm, and 0.7
      mm, respectively. CONCLUSIONS: The result reported in this study includes all
      tremor patients treated at our institution when their posttreatment MRI data were
      available for study. It represents a direct confirmation of target positioning
      accuracy in radiosurgery with a LINAC-based frameless system and its limitations.
      This level of accuracy is only achievable with an appropriate QA program in place
      for a LINAC-based frameless radiosurgery system.

PMID- 27720704
TI  - 8 Gy single-fraction radiation for bone metastases: Do the data support a 1-size
      fits-all approach?

PMID- 27720705
TI  - TGF-beta Signaling: New Insights Into Aortic Aneurysms.

PMID- 27720706
TI  - The effect of parental rejection on the emotional eating behaviour of youngsters:
      A laboratory-based study.
AB  - Results from survey studies demonstrate a relationship between parental rejection
      and self-reported emotional eating of youngsters. The aim of the current study
      was to build on this research by examining the relationship between parental
      rejection and actual emotional eating, using an experimental laboratory paradigm.
      Participants were 46 youngsters between the ages of 10 and 17 years old.
      Participants first completed online questionnaires at home, measuring parental
      rejection and emotional eating style. At the laboratory, participants were
      randomly assigned to a neutral condition or negative mood condition, followed by
      a multi-item snack buffet. The interaction effect maternal rejection * condition
      on energy intake from savoury food was significant. More maternal rejection
      predicted more energy intake from savoury food in the negative mood condition,
      but not in the neutral condition. The results highlight the importance of
      assessing, and if mandatory, improving the emotional bond between parent and
      child in the prevention and intervention of emotional eating.

PMID- 27720707
TI  - Perspectives on learning to cook and public support for cooking education
      policies in the United States: A mixed methods study.
AB  - Declines in cooking skills in the United States may contribute to poor diet
      quality and high obesity rates. Little is known about how Americans learn to cook
      or their support for cooking education policies. The objective of this study was
      to examine how Americans learn to cook, attributions of responsibility for
      teaching children how to cook, and public support for policies to teach cooking
      skills. We used a concurrent, triangulation mixed-methods design that combined
      qualitative focus group data (from 7 focus groups in Baltimore, MD (N = 53)) with
      quantitative survey data from a nationally representative, web-based survey (N =
      1112). We analyzed focus group data (using grounded theory) and survey data
      (using multivariable logistic regression). We find that relatively few Americans
      learn to cook from formal instruction in school or community cooking classes;
      rather, they primarily learn from their parents and/or by teaching themselves
      using cookbooks, recipe websites or by watching cooking shows on television.
      While almost all Americans hold parents and other family members responsible for
      teaching children how to cook, a broad majority of the public supports requiring
      cooking skills to be taught in schools either through existing health education
      (64%) or through dedicated home economics courses (67%). Slightly less than half
      of all Americans (45%) support increasing funding for cooking instruction for
      participants in the Supplemental Nutrition Assistance Program (SNAP). Broad
      public support for teaching cooking skills in schools suggests that schools are
      one promising avenue for policy action. However, school-based strategies should
      be complemented with alternatives that facilitate self-learning. More research is
      needed to identify effective means of teaching and disseminating the key cooking
      skills and knowledge that support healthy eating.

PMID- 27720709
TI  - Neutral point testing of color vision in the domestic cat.
AB  - Despite extensive study, the basic nature of feline spectral sensitivity is still
      unresolved. Most electrophysiological studies have demonstrated two photopic
      receptors within the cat's retina, one most sensitive to longer wavelengths near
      560 nm and the other most sensitive to shorter wavelengths near 460 nm, providing
      the neuroretinal basis for dichromatic vision. A few studies, however, have
      detected a third photopic receptor most sensitive to medium wavelengths between
      500 and 520 nm, overlapping in spectrally sensitivity with the feline scotopic
      receptor, that potentially could allow trichromatic vision. Indeed, one
      behavioral study has demonstrated trichromatic vision in cats, but a flaw within
      its experimental design raises the possibility that achromatic intensity cues
      might have allowed the accurate identification of medium wavelength targets. This
      study tested for a spectral neutral point in the domestic cat using a two-choice
      discrimination task. The positive targets were created using monochromatic light
      from various single wavelength light emitting diodes (LEDs) combined with a white
      light of variable intensity, while the negative targets were created using white
      light of variable intensity. Trials were performed with varying intensities of
      positive and negative targets, from brighter positive targets to brighter
      negative targets, to eliminate achromatic intensity cues. Two cats with prior
      experience with two-choice discrimination tasks, one male and one female,
      successfully discriminated monochromatic light from 456 nm to 497 nm and from 510
      nm to 524 nm, but both failed to discriminate monochromatic light at 505 nm over
      multiple trials. These results provide strong evidence that cats are dichromatic
      with a neutral point near 505 nm. This neutral point is nearly identical to the
      neutral point of the human deuteuranope, making feline vision a more accurate a
      model for red-green colorblind individuals than normal trichromats.

PMID- 27720708
TI  - Invariant natural killer T cells play dual roles in the development of
      experimental autoimmune uveoretinitis.
AB  - Experimental autoimmune uveoretinitis (EAU) represents an experimental model for
      human endogenous uveitis, which is caused by Th1/Th17 cell-mediated inflammation.
      Natural killer T (NKT) cells recognize lipid antigens and produce large amounts
      of cytokines upon activation. To examine the role of NKT cells in the development
      of uveitis, EAU was elicited by immunization with a peptide from the human
      interphotoreceptor retinoid-binding protein (hIRBP1-20) in complete Freund's
      adjuvant and histopathology scores were evaluated in C57BL/6 (WT) and NKT cell
      deficient mice. NKT cell-deficient mice developed more severe EAU pathology than
      WT mice. When WT mice were treated with ligands of the invariant subset of NKT
      cells (alpha-GalCer or RCAI-56), EAU was ameliorated in mice treated with RCAI-56
      but not alpha-GalCer. IRBP-specific Th1/Th17 cytokines were reduced in RCAI-56
      treated compared with vehicle-treated mice. Although the numbers of IRBP-specific
      T cells detected by hIRBP3-13/I-Ab tetramers in the spleen and the draining lymph
      node were the same for vehicle and RCAI-56 treatment groups, RORgammat expression
      by tetramer-positive cells in RCAI-56-treated mice was lower than in control
      mice. Moreover, the eyes of RCAI-56-treated mice contained fewer IRBP-specific T
      cells compared with control mice. These results suggest that invariant NKT (iNKT)
      cells suppress the induction of Th17 cells and infiltration of IRBP-specific T
      cells into the eyes, thereby reducing ocular inflammation. However, in sharp
      contrast to the ameliorating effects of iNKT cell activation during the
      initiation phase of EAU, iNKT cell activation during the effector phase
      exacerbated disease pathology. Thus, we conclude that iNKT cells exhibit dual
      roles in the development of EAU.

PMID- 27720710
TI  - The Nurse's Role in the Promotion of Safe Sleep for Infants.

PMID- 27720711
TI  - Posterior Reversible Encephalopathy Syndrome: A Comparative Study of Pediatric
      Versus Adult Patients.
AB  - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is an acute
      neurotoxic syndrome that, although characteristically reversible, can result in
      long-term disability. Our aim was to identify the clinical and radiological
      factors that are unique to children with PRES compared with adults with the
      syndrome in a single center. METHODS: We retrospectively reviewed the clinical
      and radiological records of all patients with PRES admitted at a tertiary care
      medical center from 2007 to 2014. All patients who met the clinical and
      radiological criteria for PRES were dichotomized into children (less than 18
      years) and adults (18 years or older) based on their age groups, and comparison
      of their baseline variables, clinical, laboratory, and imaging features was
      performed. RESULTS: During this study period, 19 pediatric patients and 100 adult
      patients with PRES were identified. On univariate analysis, factors significantly
      associated with pediatric patients with the syndrome were multiorgan failure
      (84.2% vs 50%, P = 0.006), temporal lobe involvement (63.3% vs 39%, P = 0.04),
      restricted diffusion (42.1% vs 18%, P = 0.02), and less likelihood of cerebellar
      involvement (21.1% vs 57%, P = 0.004). On bivariate logistic regression analysis,
      all these factors remained significantly associated with pediatric PRES;
      multiorgan failure (odds ratio: 5.80, 95% confidence interval: 1.45 to 29.41, P =
      0.03), temporal lobe involvement (odds ratio: 5.08, 95% confidence interval: 1.17
      to 22.17, P = 0.03), restricted diffusion (odds ratio: 2.48, 95% confidence
      interval: 1.61 to 10.10, P = 0.02), and less likely to have cerebellar
      involvement (odds ratio: 0.08, 95% confidence interval: 0.002 to 0.39, P =
      0.002). CONCLUSIONS: Factors unique to PRES in children compared with adults
      include a greater propensity with multi-organ failure, involvement of the
      temporal lobe, and restricted diffusion on imaging.

PMID- 27720712
TI  - Relapsing Acute Axonal Neuropathy in Hereditary Fructose Intolerance.
AB  - BACKGROUND: A severe neurological abnormality has not been previously described
      in individuals with hereditary fructose intolerance, which typically presents
      early in childhood with severe metabolic acidosis and hypoglycemia. PATIENT
      DESCRIPTION: We describe a boy who by age five years had required multiple
      admissions to the pediatric intensive care unit for an aggressive and atypical,
      relapsing and remitting neuropathy with features of acute motor axonal neuropathy
      (AMAN). It was later discovered that he also had undiagnosed hereditary fructose
      intolerance, and the severity and frequency of his neurological episodes
      diminished following an exclusion diet. His asymptomatic younger brother was
      diagnosed with hereditary fructose intolerance on screening. He is on a fructose
      free diet and has not developed neurological symptoms. CONCLUSIONS: Ongoing low
      level exposure to fructose prior to diagnosis may have contributed to our
      patient's neurological dysfunction. Early diagnosis and treatment may prevent
      neurological complications of hereditary fructose intolerance.

PMID- 27720713
TI  - Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor
      metastasis.
AB  - GTP binding protein 4(GTPBP4), a member of GTP-binding protein family, was
      previously characterized as a tumor suppressor that regulates and requires merlin
      to suppress cell proliferation. However, the role of GTPBP4 in the metastasis of
      colorectal carcinoma (CRC) remains unelucidated. Here, we observed that GTPBP4
      was detected at higher levels in CRC metastatic tissues than that in the primary
      tumor tissues. Notably, up-regulation of GTPBP4 was closely correlated with tumor
      metastasis in CRCs. Kaplan-Meier and multivariate Cox regression analysis
      indicated GTPBP4 as an independent prognostic factor for CRC patients (hazard
      ratio = 2.693, 95% confident interval: 1.193-6.083, p = 0.017). Functional
      studies established that knockdown of GTPBP4 impeded, whereas ectopic expression
      of GTPBP4 enhanced cell motility and tumor metastasis in CRC cells.
      Interestingly, mechanistic investigations suggested that GTPBP4 may disorganize
      actin cytoskeleton through repressing RhoA signaling. Taken together, our
      research uncovered that GTPBP4 promotes CRC metastasis by disrupting actin
      cytoskeleton, which is mediated by the reduced RhoA activity. Strategies
      targeting GTPBP4 will be promising for CRC patients with metastases.

PMID- 27720714
TI  - Visual assessment of parasitic burden in infected macrophage by plasmonic
      detection of leishmania specific marker RNA.
AB  - Visceral leishmaniasis is a neglected tropical disease and may prove fatal if not
      diagnosed and treated early. The amastigotes of Leishmania donovani nest in the
      macrophage of human host and thus, determination of parasitic burden in the
      infected macrophages has been the most crucial step in diagnosis, dose
      determination and medical management of relapse cases of this fatal disease.
      Microscopic count following Giemsa staining and other morphological analysis are
      the classical ways vastly used in the resource stringent endemic areas. The
      current method introduced a high throughput, rapid, cheap, non-gel, non-PCR and
      nonculture based visual detection platform employing salt triggered aggregation
      of gold nanoparticle in presence of extracted total RNA from infected macrophages
      and leishmania specific oligo-nucleotide probe to determine the parasite burden
      in macrophages. Amastigote's small subunit ribosomal RNA (SSU rRNA, PMID 1565128)
      was used as the leishmania specific marker and its abundance in the total RNA
      extracts of infected macrophages were determined by this visual colorimetric
      assay.

PMID- 27720715
TI  - miR-216b suppresses breast cancer growth and metastasis by targeting SDCBP.
AB  - Breast cancer is the most deadly cancer among women and the second leading cause
      of cancer death worldwide. Treatment effectiveness is complicated with tumor
      invasiveness/drug resistance. To tailor treatments more effectively to individual
      patients, it is important to define tumor growth and metastasis at molecular
      levels. SDCBP is highly overexpressed and associated with a strikingly poor
      prognosis in breast cancer. However the post transcriptional regulation of SDCBP
      overexpression remains to be an unexplored area. Our study reveals that miR-216b
      directly regulates SDCBP expression by binding to its 3'UTR region. miR-216b is a
      tumor suppressive miRNA and it is underexpressed during metastatic breast cancer.
      Consequently, overexpression of miR-216b resulted in decreased proliferation,
      migration and invasion in BC cell lines by modulating the expression of SDCBP.
      Inhibition of miR-216b divergent the tumor suppressive role by inducing the
      growth proliferation, migration and invasion in vitro. There is therefore a
      negative correlation between the expression of miR-216b and its target gene SDCBP
      in the BC tissue samples as well as cell lines. Simultaneous expression of miR
      216b and SDCBP rescued the growth, migration and invasion effect suggesting that
      tumor suppressive action of miR-216b may be directly mediated by SDCBP. In
      summary, the study identifies miR-216b as a regulator of SDCBP expression in
      breast cancer which can potentially be targeted for developing newer therapies
      for the effective treatment of this killer disease.

PMID- 27720717
TI  - A variety of human monoclonal antibodies against epidermal growth factor receptor
      isolated from a phage antibody library.
AB  - When the technology for constructing human antibody (Ab) libraries using a phage
      display system was developed, many researchers in Ab-related fields anticipated
      that it would be widely applied to the development of pharmaceutical drugs
      against various diseases, including cancers. However, successful examples of such
      applications are very limited. Moreover, researchers who utilize phage-display
      technology now show divergent ways of thinking about phage Ab libraries. For
      example, there is debate about what should be the source of VH and VL genes for
      the construction of libraries to cover the whole repertoire of Abs present in the
      human body. In the immune system, the introduction of mutations into V genes
      followed by selection based on binding activity, termed Ab maturation, is
      required for the production of Abs exhibiting high affinity to the antigen (Ag).
      Therefore, introduction of mutations and selection are required for isolation of
      Abs with high affinity after isolation of clones from phage Ab libraries. We
      constructed a large human Ab library termed AIMS, developed a screening method
      termed ICOS, and succeeded in isolating many human monoclonal Abs (mAbs) that
      specifically and strongly bind to various tumor-associated Ags. Eight anti-EGFR
      mAbs were included, which we characterized. These mAbs showed various different
      activities against EGFR-expressing cancer cells. In this paper, we describe these
      data and discuss the possibility and necessity that the mAbs isolated from the
      AIMS library might be developed as therapeutic drugs against cancers without
      introduction of mutations.

PMID- 27720716
TI  - Possible pathogenic engagement of soluble Semaphorin 4D produced by gammadeltaT
      cells in medication-related osteonecrosis of the jaw (MRONJ).
AB  - Prior consensus held that medication-related osteonecrosis of the jaw (MRONJ)
      lesion was composed of necrotic bone; however, more recent studies have
      identified inflammatory infiltrates in the lesion. Herein, we report that
      remarkably elevated infiltrating gammadeltaT cells (90% of lymphocytes) express
      Semaphorin 4D (Sema4D) in human patient with MRONJ lesion, whereas gammadeltaT
      cells only account for 2-5% of lymphocytes in blood. Importantly, Sema4D is
      implicated in the pathogenesis of T cell-mediated inflammatory diseases, such as
      rheumatoid arthritis and multiple sclerosis. Indeed, in a mouse model of MRONJ,
      an elevated number of gammadeltaT, but not alphabetaT, cells infiltrating in the
      MRONJ-like lesion was observed. Both elevated soluble Sema4D (sSema4D) production
      accompanied by pro-inflammatory cytokines, including TNF-alpha IFN-gamma and IL
      1beta, and Sema4D-expressing gammadeltaT cells were detected in mouse MRONJ-like
      lesion. Activated gammadeltaT cells produced sSema4D in vitro, which could
      promote TNF-alpha production from macrophages. Meanwhile, gammadeltaT cell-KO
      mice were resistant to the induction of MRONJ and, hence, showed no elevation of
      local productions of Sema4D and TNF-alpha. Finally, systemic administration of
      anti-Sema4D neutralizing mAb suppressed the onset of MRONJ in wild-type mice in
      conjunction with diminished level of TNF-alpha. These results suggested a
      critical pathogenic engagement of Sema4D produced by gammadeltaT cells in the
      development of MRONJ.

PMID- 27720718
TI  - Therapeutic efficacy of an anti-PD-L1 antibody based immunocytokine in a
      metastatic mouse model of colorectal cancer.
AB  - Immunocytokines (antibody-cytokine fusions) have been proved to be a promising
      class of therapeutic agents for tumors. Anti-PD-L1 antibodies or IL-2 have been
      used to treat a variety of cancers. Here, in order to remove T cell inhibition
      and increasing the IL-2 concentration in the tumor microenvironment, we
      engineered a novel anti-PD-L1 antibody based immunocytokine by fusing hIL-2 to
      the C-Term of atezolizumab, denoted as BIPI. Our results revealed that BIPI was
      effective in stimulating T cell activation in vitro and could selectively
      localize to the tumor. Furthermore, tumor regression and prolonged survival were
      also observed in the metastatic colorectal cancer mouse model. The obviously
      longer survival mice in BIPI treatment group turned out depending on the function
      of CD8+ T cells. The IFN- secreted from CD8+ T cells in the spleen also
      contributed to the better tumor inhibition profile in BIPI treatment group than
      in anti-PD-L1 or IL-2 treatment alone. Taken together, our data evidenced the
      enhanced antitumor potency of BIPI, suggesting its potential use for cancers with
      a low response to the anti-PD-L1 or IL-2 treatment.

PMID- 27720719
TI  - History of antimicrobial drug discovery: Major classes and health impact.
AB  - The introduction of antibiotics into clinical practice revolutionized the
      treatment and management of infectious diseases. Before the introduction of
      antibiotics, these diseases were the leading cause of morbidity and mortality in
      human populations. This review presents a brief history of discovery of the main
      antimicrobial classes (arsphenamines, beta-lactams, sulphonamides, polypeptides,
      aminoglycosides, tetracyclines, amphenicols, lipopeptides, macrolides,
      oxazolidinones, glycopeptides, streptogramins, ansamycins, quinolones, and
      lincosamides) that have changed the landscape of contemporary medicine. Given
      within a historical timeline context, the review discusses how the introduction
      of certain antimicrobial classes affected the morbidity and mortality rates due
      to bacterial infectious diseases in human populations. Problems of resistance to
      antibiotics of different classes are also extensively discussed.

PMID- 27720720
TI  - Comparative Evaluation of Condylar Volume Between Patients With Unilateral
      Condylar Hyperplasia and Class III Dentofacial Deformity.
AB  - PURPOSE: To compare the condylar volume of patients with unilateral condylar
      hyperplasia (UCH) with that of patients with a Class III skeletal relation.
      MATERIALS AND METHODS: Twenty cone-beam computed tomograms of patients were
      analyzed. Images were divided into 2 groups: 10 from patients with transverse
      asymmetry of the face and 10 from patients with a Class III facial deformity.
      Patients' ages ranged from 15 to 30 years. Volumetric data were reconstructed
      using Dolphin 3D software (Dolphin Imaging & Management Solutions, Chatsworth,
      CA). This software measured the condylar volume above the deepest point of the
      sigmoid notch, the lower arch midline deviation, and the overjet. RESULTS: The
      condyle with hyperplasia exhibited the largest volume (1.97 +/- 0.52 cm3) and a
      statistically significant difference compared with the contralateral condyle
      (chi2 = 14.30; P < .01). The Class III condyle exhibited relative symmetry of
      volume between the left and right sides. These condyles exhibited a larger volume
      compared with the non-hyperplastic condyles in the UCH group, with a
      statistically significant difference (chi2 = 6.22; P = .013; chi2 = 5.50; P =
      .019). CONCLUSIONS: Hyperplastic condyles were similar in volume to the condyles
      of patients with mandibular prognathism, suggesting that patients with a Class
      III skeletal relation could exhibit bilateral condylar hyperplasia.

PMID- 27720721
TI  - What Name Best Represents Our Specialty? Oral and Maxillofacial Surgeon Versus
      Oral and Facial Surgeon.
AB  - PURPOSE: To determine whether changing "oral and maxillofacial surgeon" (OMS) to
      "oral and facial surgeon" improves the perception and awareness of the OMS's role
      and surgical scope of practice in undergraduate biomedical and dental students.
      MATERIALS AND METHODS: This cross-sectional study requested undergraduate and
      dental students to select 1 of 5 specialists to treat 21 conditions. Two
      different surveys were presented: 1 designating specialists as "oral and
      maxillofacial surgeons" and 1 designating specialists as "oral and facial
      surgeons." The independent variable was the specialist "oral and maxillofacial
      surgeon" or "oral and facial surgeon." The dependent variables included
      specialists chosen for the procedure (ear, nose, and throat surgeon; OMS vs oral
      and facial surgeon; plastic surgeon; periodontist; and "other"). The test of
      proportions (z test) with the Yates correction was performed. RESULTS: The sample
      was composed of 1,671 undergraduate upper division science students and 568
      senior dental students. Results showed that undergraduate students' perception of
      an OMS's surgical scope increased significantly from 28 to 33% when "oral and
      facial surgeon" was used instead of "oral and maxillofacial surgeon." Dental
      students' perception of an OMS's surgical scope remained the same whether "oral
      and maxillofacial surgeon" or "oral and facial surgeon" was used. CONCLUSION: The
      results of this study suggest that using "oral and facial surgeon" instead of
      "oral and maxillofacial surgeon" increases awareness of an OMS's surgical scope
      of practice in undergraduate upper division science students, which could be an
      important step toward increasing the recognition of the profession by the general
      public and other non-dental medical colleagues.

PMID- 27720722
TI  - Compartmentalization of the Cell Membrane.
AB  - Many cell-membrane-associated processes require transient spatiotemporal
      separation of components on scales ranging from a couple of molecules to
      micrometers in size. Understanding these processes mechanistically involves
      understanding how lipids and proteins self-organize and interact with the cell
      cortex. Here, we review recent advances in dissecting the mechanisms of cell
      membrane compartmentalization. We introduce the challenges in studying cell
      membrane organization, the current understanding of how complex membranes self
      organize to form transient domains, and the role of protein scaffolds in membrane
      organization. We discuss the formation of signaling domains as an important
      example of transient membrane compartmentalization. We conclude by pointing to
      the current limitations of measuring membrane organization in living cells and
      the steps that are required to advance the field.

PMID- 27720724
TI  - Brain oscillations and connectivity in autism spectrum disorders (ASD): new
      approaches to methodology, measurement and modelling.
AB  - Although atypical social behaviour remains a key characterisation of ASD, the
      presence of sensory and perceptual abnormalities has been given a more central
      role in recent classification changes. An understanding of the origins of such
      aberrations could thus prove a fruitful focus for ASD research. Early
      neurocognitive models of ASD suggested that the study of high frequency activity
      in the brain as a measure of cortical connectivity might provide the key to
      understanding the neural correlates of sensory and perceptual deviations in ASD.
      As our review shows, the findings from subsequent research have been
      inconsistent, with a lack of agreement about the nature of any high frequency
      disturbances in ASD brains. Based on the application of new techniques using more
      sophisticated measures of brain synchronisation, direction of information flow,
      and invoking the coupling between high and low frequency bands, we propose a
      framework which could reconcile apparently conflicting findings in this area and
      would be consistent both with emerging neurocognitive models of autism and with
      the heterogeneity of the condition.

PMID- 27720723
TI  - Direct loop mediated isothermal amplification on filters for quantification of
      Dehalobacter in groundwater.
AB  - Nucleic acid amplification of biomarkers is increasingly used to monitor
      microbial activity and assess remedial performance in contaminated aquifers.
      Previous studies described the use of filtration, elution, and direct isothermal
      amplification (i.e. no DNA extraction and purification) as a field-able means to
      quantify Dehalococcoides spp. in groundwater. This study expands previous work
      with direct loop mediated isothermal amplification (LAMP) for the detection and
      quantification of Dehalobacter spp. in groundwater. Experiments tested
      amplification of DNA with and without crude lysis and varying concentrations of
      humic acid. Three separate field-able methods of biomass concentration with eight
      aquifer samples were also tested, comparing direct LAMP with traditional DNA
      extraction and quantitative PCR (qPCR). A new technique was developed where
      filters were amplified directly within disposable Gene-Z chips. The direct filter
      amplification (DFA) method eliminated an elution step and provided a detection
      limit of 102Dehalobacter cells per 100mL. LAMP with crudely lysed Dehalobacter
      had a negligible effect on threshold time and sensitivity compared to lysed
      samples. The LAMP assay was more resilient than traditional qPCR to humic acid in
      sample, amplifying with up to 100mg per L of humic acid per reaction compared to
      1mg per L for qPCR. Of the tested field-able concentrations methods, DFA had the
      lowest coefficient of variation among Dehalobacter spiked groundwater samples and
      lowest threshold time indicating high capture efficiency and low inhibition.
      While demonstrated with Dehalobacter, the DFA method can potentially be used for
      a number of applications requiring field-able, rapid (<60min) and highly
      sensitive quantification of microorganisms in environmental water samples.

PMID- 27720725
TI  - Glycation gap: An additional tool for glycometabolic monitoring.
AB  - BACKGROUND: The determination of glycated albumin (GA) has been suggested as an
      additional parameter having an independent added value respect to that of HbA1c.
      The determination of glycation gap (gg) has also been proposed, but few studies
      have addressed its potential impact in the routine evaluation of glycometabolic
      control. METHODS: A total of 157 subjects presenting normal whole blood cell
      count, no hemoglobin variants, normal creatinine levels and serum protein
      electrophoresis patterns were studied. In a second phase, a total of 205 subjects
      with no restrictions as those of the first phase study, were analyzed. HbA1cwas
      measured by capillary electrophoresis, glycated albumin by an enzymatic method
      and their gg were then calculated. RESULTS: The correlation between HbA1c and GA
      for the subjects of phase 1 was strong (r=0.8927) and significant correlation
      between gg and age was remarked (r=0.4486). We found 17.1% of phase 2 subjects
      with gg falling outside the 95% prediction intervals. Various clinical conditions
      seemed to affect these subjects, in our experience mostly often related to
      impaired renal function. CONCLUSION: The glycation gap may be useful to alert
      clinicians about patients under unstable glycemic control or when various pre
      analytical conditions my affect the reliability of the measurement of GA or
      HbA1c.

PMID- 27720727
TI  - Comments about: "Central giant cell granuloma in children: Presentation of
      different therapeutic options".

PMID- 27720726
TI  - Biomarkers of Morbid Obesity and Prediabetes by Metabolomic Profiling of Human
      Discordant Phenotypes.
AB  - Metabolomic studies aimed to dissect the connection between the development of
      type 2 diabetes and obesity are still scarce. In the present study, fasting serum
      from sixty-four adult individuals classified into four sex-matched groups by
      their BMI [non-obese versus morbid obese] and the increased risk of developing
      diabetes [prediabetic insulin resistant state versus non-prediabetic non-insulin
      resistant] was analyzed by LC- and FIA-ESI-MS/MS-driven metabolomic approaches.
      Altered levels of [lyso]glycerophospholipids was the most specific metabolic
      trait associated to morbid obesity, particularly lysophosphatidylcholines
      acylated with margaric, oleic and linoleic acids [lysoPC C17:0: R=-0.56,
      p=0.0003; lysoPC C18:1: R=-0.61, p=0.0001; lysoPC C18:2 R=-0.64, p<0.0001].
      Several amino acids were biomarkers of risk of diabetes onset associated to
      obesity. For instance, glutamate significantly associated with fasting insulin
      [R=0.5, p=0.0019] and HOMA-IR [R=0.46, p=0.0072], while glycine showed negative
      associations [fasting insulin: R=-0.51, p=0.0017; HOMA-IR: R=-0.49, p=0.0033],
      and the branched chain amino acid valine associated to prediabetes and insulin
      resistance in a BMI-independent manner [fasting insulin: R=0.37, p=0.0479; HOMA
      IR: R=0.37, p=0.0468]. Minority sphingolipids including specific
      [dihydro]ceramides and sphingomyelins also associated with the prediabetic
      insulin resistant state, hence deserving attention as potential targets for early
      diagnosis or therapeutic intervention.

PMID- 27720728
TI  - Cloning of two carboxylesterase cDNAs from the swimming crab Portunus
      trituberculatus: Molecular evidences for their putative roles in methyl
      farnesotae degradation.
AB  - The sesquiterpenoid methyl farnesoate (MF) is the unepoxidized form of insect
      juvenile hormone (JH) III, and is considered an equivalent of JH in crustaceans.
      Degradation of MF is similar to that of JH which occurs through ester hydrolysis
      by specific carboxylesterases (CXEs). In this study, the full-length cDNAs of two
      JH esterase-like CXEs were cloned from the swimming crab, Portunus
      trituberculatus. The predicted amino acid sequences of the two PtCXEs contain the
      conserved motifs including catalytic triad and oxyanion hole, which are the
      hallmark of the CXE family proteins. The phylogenetic analysis showed that the
      two PtCXEs may belong to the hormone/semiochemical processing group of CXE
      family, indicating their possible roles on metabolism of hormones. Transcripts of
      both PtCXEs were most abundant in hepatopancreas and the PtCXE2 was also highly
      expressed in ovary. The mRNA levels of two PtCXEs in hepatopancreas were induced
      by in vivo MF treatment and eyestalk ablation, further indicating their potential
      in degrading MF. However, during the ovarian maturation, expression of the two
      PtCXEs increased significantly in the early-vitellogenic stage, prior to the
      remarkable rise in hemolymph MF titer reported by our previous studies. Taken
      together, our results suggest that the two PtCXEs can potentially serve as the MF
      esterases, but their catalytic activity may not be restricted to MF.

PMID- 27720729
TI  - The importance of correctly identifying the process responsible for spatial
      genetic structure in Leopard: A response to McManus and Smuts (2016).
AB  - Microsatellite analyses suggest that spatial genetic structure among six leopard
      sampling sites in southern Africa is the result of isolation by distance.

PMID- 27720730
TI  - No definite clinical features of immunoglobulin G4-related disease in patients
      with pulmonary nodular lymphoid hyperplasia.
AB  - Pulmonary nodular lymphoid hyperplasia (PNLH) may show heavy lymphoplasmacytic
      infiltrates with increased immunoglobulin G4 (IgG4)-positive plasma cells as in
      IgG4-related disease (IgG4-RD). However, it is unclear whether PNLH could be a
      manifestation of IgG4-RD. A recent study reported the presence of Epstein-Barr
      virus (EBV) in IgG4-related lymphadenopathy. We postulated that a subset of PNLH
      might represent IgG4-related lung disease with EBV-positive lymphocytes as has
      been reported in IgG4-related lymphadenopathy. IgG and IgG4
      immunohistochemistries were performed on 26 PNLH cases in our files (1994-2014)
      and on 9 controls including diffuse lymphoid hyperplasia of the lung without
      nodularity (n=2), usual interstitial pneumonia with increased lymphoplasmacytic
      infiltrates (n=5), and thoracic lymphadenopathy (n=2). EBV in situ hybridization
      was performed in the cases with the highest IgG4+ count (n=15). Median IgG4+
      plasma cell count in PNLH was 36 cells per high-power field (interquartile range,
      7-65) with median IgG4+/IgG+ ratio of 0.24 (interquartile range, 0.12-0.37).
      Three of 26 cases had a markedly increased IgG4+ count (range, 55-139) and
      IgG4+/IgG+ ratio (>0.4). Serum IgG4 level available in 1 of these cases was not
      elevated, and all 3 patients had alternate medical diagnoses. Absolute counts of
      IgG4+ plasma cells in PNLH did not significantly differ from the other control
      groups. Result of EBV in situ hybridization was negative in all cases tested. In
      conclusion, most PNLH cases had low IgG4+ cells, and there was no clinical
      evidence of IgG4-RD or EBV among those with increased IgG4+ cells.

PMID- 27720731
TI  - Upgrading and upstaging at radical prostatectomy in the post-prostate-specific
      antigen screening era: an effect of delayed diagnosis or a shift in patient
      selection?
AB  - Prostate cancer management changed in recent times given the recommendation
      against prostate-specific antigen screening, adherence to active surveillance,
      and "cytoreductive" surgery. We hypothesized that radical prostatectomy (RP)
      findings changed as well. All consecutive RPs (n=1348) and first time prostate
      needle biopsies (n=1719) in a period of 9 years were reviewed. The cohort was
      separated into 3 groups: (1) from May 2006 to April 2009, (2) from May 2009 to
      April 2012, and (3) from May 2012 to April 2015. The number of RPs decreased 15%
      from 551 in group 1 to 476 in group 2 and decreased a further 35% to 311 in group
      3. Pure Gleason 6 (grade group 1) decreased from 46% in group 1 to 24% in group 2
      (P<.001) to 12% in group 3 (P<.001). Gleason score 4+3=7 (grade group 3)
      increased from 9.8% in group 1 to 13.4% in group 2 (P=.07) to 20.6% in group 3
      (P=.01). Gleason score 8, 9, or 10 (grade groups 4 and 5) increased from 0.9% in
      group 1 to 8.4% in group 2 (P<.001) to 13.2% in group 3 (P=.04). Pathologic stage
      pT3 or above increased from 15.5% in group 1 to 29.2% in group 2 (P<.01) to 38.3%
      in group 3 (P=.01). In needle biopsies, there was no difference in number of
      cancer diagnoses, number of positive cores, or distribution of grades among 3
      groups. More patients with low-risk disease are opting for active surveillance,
      and patients with high-risk disease are offered cytoreductive surgery. Lack of
      similar changes in needle biopsies suggests that a decrease in screening is not
      playing a role in the changes seen at RPs.

PMID- 27720732
TI  - Role of fibrogenesis of gastroesophageal reflux and microaspiration in a patient
      with 12 years radiologic follow-up-reply.

PMID- 27720734
TI  - Role of fibrogenesis of gastroesophageal reflux and microaspiration in a patient
      with 12 years of radiologic follow-up.

PMID- 27720733
TI  - Reproducibility of SOX-11 detection in decalcified bone marrow tissue in mantle
      cell lymphoma patients.
AB  - Mantle cell lymphoma (MCL) usually harbors the t(11;14)(q13;q32) with
      overexpression of CCND1 mRNA and transcription of the cyclin D1 nuclear protein.
      Regardless of CCND1 status, most MCLs also express the SOX11 nuclear protein,
      which is thus helpful in the diagnosis of the rare CCND1-negative MCLs. Recently,
      SOX11 has been reported to be often negative in MCLs clinically resembling
      marginal zone lymphoma and recently defined as "leukemic non-nodal" MCL in the
      incoming revision of the WHO classification of lymphoid tumors, for which the
      bone marrow biopsy is commonly the first diagnostic approach. Due to the less
      aggressive clinical behavior of the latter MCLs, the reliable determination of
      the SOX11 antigen in decalcified tissue is mandatory. To this end, since little
      data are available in the literature, four commercially available anti-SOX11
      antibodies (two polyclonal and two monoclonal) were tested on 21 positive staging
      bone marrow (BM) biopsies from cyclin D1/SOX11-positive MCL patients (17 fixed in
      B5, 4 in 10% buffered formalin) and on 9 positive BM biopsies from leukemic non
      nodal MCL patients. The results were compared for specificity, sensitivity,
      staining strength and degree of an additional staining on myeloid precursors,
      also evaluating possible impact of the different fixatives used. Non-mantle cell
      lymphomas were also tested to address specificity. All reagents showed high
      sensitivity but the monoclonal code CMC38221001 provided the highest specificity
      and the lowest degree of non-lymphoid staining on myeloid cells. Formalin
      fixation generally improved the performance of most antibodies when compared to
      B5 fixation.

PMID- 27720735
TI  - Hypothalamic-pituitary-adrenal axis function in Fragile X Syndrome and its
      relationship to behaviour: A systematic review.
AB  - Fragile X Syndrome (FXS) is characterised by features including anxiety and
      autistic-like behaviour, which led to early hypotheses that aberrant
      physiological arousal may underlie the behavioural phenotype. In line with this,
      several lines of evidence suggest that the hypothalamic-pituitary-adrenal (HPA)
      axis may be altered in the syndrome. This review collates evidence to determine
      the nature of HPA axis baseline activity and reactivity (as measured by
      glucocorticoid levels) differences in FXS, and its relationship to behaviour.
      Through a search of electronic databases, 15 papers were identified which
      provided data on humans with FXS or the FMR1 knockout mouse model. The findings
      across studies are mixed, though trends in the findings can be seen, including
      elevations in cortisol levels, particularly in males. Preliminary findings also
      highlight associations between cortisol levels and key behaviours associated with
      the syndrome, such as gaze avoidance. Areas for future research are discussed.

PMID- 27720736
TI  - The effect of a crunchy pseudo-chewing sound on perceived texture of softened
      foods.
AB  - Elderly individuals whose ability to chew and swallow has declined are often
      restricted to unpleasant diets of very soft food, leading to a poor appetite. To
      address this problem, we aimed to investigate the influence of altered auditory
      input of chewing sounds on the perception of food texture. The modified chewing
      sound was reported to influence the perception of food texture in normal foods.
      We investigated whether the perceived sensations of nursing care foods could be
      altered by providing altered auditory feedback of chewing sounds, even if the
      actual food texture is dull. Chewing sounds were generated using electromyogram
      (EMG) of the masseter. When the frequency properties of the EMG signal are
      modified and it is heard as a sound, it resembles a "crunchy" sound, much like
      that emitted by chewing, for example, root vegetables (EMG chewing sound). Thirty
      healthy adults took part in the experiment. In two conditions (with/without the
      EMG chewing sound), participants rated the taste, texture and evoked feelings of
      five kinds of nursing care foods using two questionnaires. When the "crunchy" EMG
      chewing sound was present, participants were more likely to evaluate food as
      having the property of stiffness. Moreover, foods were perceived as rougher and
      to have a greater number of ingredients in the condition with the EMG chewing
      sound, and satisfaction and pleasantness were also greater. In conclusion, the
      "crunchy" pseudo-chewing sound could influence the perception of food texture,
      even if the actual "crunchy" oral sensation is lacking. Considering the effect of
      altered auditory feedback while chewing, we can suppose that such a tool would be
      a useful technique to help people on texture-modified diets to enjoy their food.

PMID- 27720737
TI  - Relational and procedural memory systems in the goldfish brain revealed by trace
      and delay eyeblink-like conditioning.
AB  - The presence of multiple memory systems supported by different neural substrata
      has been demonstrated in animal and human studies. In mammals, two variants of
      eyeblink classical conditioning, differing only in the temporal relationships
      between the conditioned stimulus (CS) and the unconditioned stimulus (US), have
      been widely used to study the neural substrata of these different memory systems.
      Delay conditioning, in which both stimuli coincide in time, depends on a non
      relational memory system supported by the cerebellum and associated brainstem
      circuits. In contrast, trace conditioning, in which a stimulus-free time gap
      separates the CS and the US, requires a declarative or relational memory system,
      thus depending on forebrain structures in addition to the cerebellum. The
      distinction between the explicit or relational and the implicit or procedural
      memory systems that support trace and delay classical conditioning has been
      extensively studied in mammals, but studies in other vertebrate groups are
      relatively scarce. In the present experiment we analyzed the differential
      involvement of the cerebellum and the telencephalon in delay and trace eyeblink
      like classical conditioning in goldfish. The results show that whereas the
      cerebellum lesion prevented the eyeblink-like conditioning in both procedures,
      the telencephalon ablation impaired exclusively the acquisition of the trace
      conditioning. These data showing that comparable neural systems support delay and
      trace eyeblink conditioning in teleost fish and mammals suggest that these
      separate memory systems and their neural bases could be a shared ancestral brain
      feature of the vertebrate lineage.

PMID- 27720738
TI  - Reply.

PMID- 27720739
TI  - An Unusual Cause of Gastritis.

PMID- 27720740
TI  - An Unusual Cause of Obscure Gastrointestinal Bleeding.

PMID- 27720742
TI  - Neural correlates of sample-coding and reward-coding in the delay activity of
      neurons in the entopallium and nidopallium caudolaterale of pigeons (Columba
      livia).
AB  - We recorded neuronal activity from the nidopallium caudolaterale, the avian
      equivalent of mammalian prefrontal cortex, and the entopallium, the avian
      equivalent of the mammalian visual cortex, in four birds trained on a
      differential outcomes delayed matching-to-sample procedure in which one sample
      stimulus was followed by reward and the other was not. Despite similar incidence
      of reward-specific and reward-unspecific delay cell types across the two areas,
      overall entopallium delay activity occurred following both rewarded and non
      rewarded stimuli, whereas nidopallium caudolaterale delay activity tended to
      occur following the rewarded stimulus but not the non-rewarded stimulus. These
      findings are consistent with the view that delay activity in entopallium
      represents a code of the sample stimulus whereas delay activity in nidopallium
      caudolaterale represents a code of the possibility of an upcoming reward.
      However, based on the types of delay cells encountered, cells in NCL also code
      the sample stimulus and cells in ENTO are influenced by reward. We conclude that
      both areas support the retention of information, but that the activity in each
      area is differentially modulated by factors such as reward and attentional
      mechanisms.

PMID- 27720741
TI  - International consensus recommendations for difficult biliary access.

PMID- 27720743
TI  - Cognitive correlates of spatial navigation: Associations between executive
      functioning and the virtual Morris Water Task.
AB  - Although effective spatial navigation requires memory for objects and locations,
      navigating a novel environment may also require considerable executive resources.
      The present study investigated associations between performance on the virtual
      Morris Water Task (vMWT), an analog version of a nonhuman spatial navigation
      task, and neuropsychological tests of executive functioning and spatial
      performance in 75 healthy young adults. More effective vMWT performance (e.g.,
      lower latency and distance to reach hidden platform, greater distance in goal
      quadrant on a probe trial, fewer path intersections) was associated with better
      verbal fluency, set switching, response inhibition, and ability to mentally
      rotate objects. Findings also support a male advantage in spatial navigation,
      with sex moderating several associations between vMWT performance and executive
      abilities. Overall, we report a robust relationship between executive functioning
      and navigational skill, with some evidence that men and women may differentially
      recruit cognitive abilities when navigating a novel environment.

PMID- 27720744
TI  - The association of serotonin receptor 3A methylation with maternal violence
      exposure, neural activity, and child aggression.
AB  - BACKGROUND: Methylation of the serotonin 3A receptor gene (HTR3A) has been linked
      to child maltreatment and adult psychopathology. The present study examined
      whether HTR3A methylation might be associated with mothers' lifetime exposure to
      interpersonal violence (IPV), IPV-related psychopathology, child disturbance of
      attachment, and maternal neural activity. METHODS: Number of maternal lifetime
      IPV exposures and measures of maternal psychopathology including posttraumatic
      stress disorder (PTSD), major depression and aggressive behavior (AgB), and a
      measure of child attachment disturbance known as "secure base distortion" (SBD)
      were assessed in a sample of 35 mothers and children aged 12-42 months. Brain
      fMRI activation was assessed in mothers using 30-s silent film excerpts depicting
      menacing adult male-female interactions versus prosocial and neutral
      interactions. Group and continuous analyses were performed to test for
      associations between clinical and fMRI variables with DNA methylation. RESULTS:
      Maternal IPV exposure-frequency was associated with maternal PTSD; and maternal
      IPV-PTSD was in turn associated with child SBD. Methylation status of several CpG
      sites in the HTR3A gene was associated with maternal IPV and IPV-PTSD severity,
      AgB and child SBD, in particular, self-endangering behavior. Methylation status
      at a specific CpG site (CpG2_III) was associated with decreased medial prefrontal
      cortical (mPFC) activity in response to film-stimuli of adult male-female
      interactions evocative of violence as compared to prosocial and neutral
      interactions. CONCLUSIONS: Methylation status of the HTR3A gene in mothers is
      linked to maternal IPV-related psychopathology, trauma-induced brain activation
      patterns, and child attachment disturbance in the form of SBD during a sensitive
      period in the development of self-regulation.

PMID- 27720745
TI  - SHH ventralizes the otocyst by maintaining basal PKA activity and regulating GLI3
      signaling.
AB  - During development of the inner ear, secreted morphogens act coordinately to
      establish otocyst dorsoventral polarity. Among these, Sonic hedgehog (SHH) plays
      a critical role in determining ventral polarity. However, how this extracellular
      signal is transduced intracellularly to establish ventral polarity is unknown. In
      this study, we show that cAMP dependent protein kinase A (PKA) is a key
      intracellular factor mediating SHH signaling through regulation of GLI3
      processing. Gain-of-function experiments using targeted gene transfection by
      sonoporation or electroporation revealed that SHH signaling inactivates PKA,
      maintaining a basal level of PKA activity in the ventral otocyst. This, in turn,
      suppresses partial proteolytic processing of GLI3FL, resulting in a low
      GLI3R/GLI3FL ratio in the ventral otocyst and the expression of ventral-specific
      genes required for ventral otocyst morphogenesis. Thus, we identify a molecular
      mechanism that links extracellular and intracellular signaling, determines early
      ventral polarity of the inner ear, and has implications for understanding the
      integration of polarity signals in multiple organ rudiments regulated by
      gradients of signaling molecules.

PMID- 27720746
TI  - The role of the autonomic nervous system in control of cardiac and air-breathing
      responses to sustained aerobic exercise in the African sharptooth catfish Clarias
      gariepinus.
AB  - Clarias gariepinus is a facultative air-breathing catfish that exhibits changes
      in heart rate (fH) associated with air-breaths (AB). A transient bradycardia
      prior to the AB is followed by sustained tachycardia during breath-hold. This
      study evaluated air-breathing and cardiac responses to sustained aerobic exercise
      in juveniles (total length~20cm), and how exercise influenced variations in fH
      associated with AB. In particular, it investigated the role of adrenergic and
      cholinergic control in cardiac responses, and effects of pharmacological
      abolition of this control on air-breathing responses. Sustained exercise at 15,
      30 and 45cms-1 in a swim tunnel caused significant increases in fAB and fH, from
      approximately 5breathsh-1 and 60heartbeatsmin-1 at the lowest speed, to over
      60breathsh-1 and 100beatsmin-1 at the highest, respectively. There was a
      progressive decline in the degree of variation in fH, around each AB, as fAB
      increased with exercise intensity. Total autonomic blockade abolished all
      variation in fH during exercise, and around each AB, but fAB responses were the
      same as in untreated animals. Cardiac responses were exclusively due to
      modulation of inhibitory cholinergic tone, which varied from >100% at the lowest
      speed to <10% at the highest. Cholinergic blockade had no effect on fAB compared
      to untreated fish. Excitatory beta-adrenergic tone was approximately 20% and did
      not vary with swimming speed, but its blockade increased fAB at all speeds,
      compared to untreated animals. This reveals complex effects of autonomic control
      on air-breathing during exercise in C. gariepinus, which deserve further
      investigation.

PMID- 27720747
TI  - Commentary on 'Impact of Shaggy Aorta in Patients with Abdominal Aortic Aneurysm
      Following Open or Endovascular Aneurysm Repair'.

PMID- 27720748
TI  - Contributions of personality dimensions to spontaneous and deliberate information
      processing in the guilty actions test.
AB  - The contribution of the Big-Five personality dimensions and locus of control to
      examinees' physiological responses in the Concealed Information polygraph Test
      (CIT) was examined for the first time. One hundred and twenty undergraduate
      students who completed Big Five personality and locus of control questionnaires
      were instructed to commit a mock theft. They were subsequently tested in the
      Guilty Actions polygraph Test, a modified version of the CIT. Each of the six
      sets of items (questions) was repeated twice. Results showed that introversion
      predicted enhanced Skin Conductance Responses (SCRs) to the critical items only
      for the first repetition of the first 3 questions which was explained by
      sensitivity to orienting responses. In contrast, extraversion was linked to
      Finger Pulse Waveform Length (FPWL) responses to the first repetition of the
      first 3 questions and was explained by extended and more deliberate information
      processing due to increased interest in the experiment. Participants high in
      openness to experience, characterized by intellectual curiosity, responded more
      strongly on FPWL throughout the test. Lower Neuroticism scores predicted enhanced
      Respiration Line Length (RLL) responses in the first repetition of the first 3
      questions. Internal locus of control predicted higher tonic skin conductance
      level before and throughout the test. Results were explained by different
      information processing styles associated with these personality dimensions during
      various stages of the test.

PMID- 27720750
TI  - Specificity characterization of the alpha-mating factor hormone by Kex2 protease.
AB  - Kex2 is a Ca2+-dependent serine protease from S. cerevisiae. Characterization of
      the substrate specificity of Kex2 is of particular interest because this protease
      serves as the prototype of a large family of eukaryotic subtilisin-related
      proprotein-processing proteases that cleave sites consisting of pairs or clusters
      of basic residues. Our goal was to study the prime region subsite S' of Kex2
      because previous studies have only taken into account non-prime sites using AMC
      substrates but not the specificity of prime sites identified through structural
      modeling or predicted cleavage sites. Therefore, we used peptides derived from
      Abz-KR?EADQ-EDDnp and Abz-YKR?EADQ-EDDnp based on the pro-alpha-mating factor
      sequence. The specificity of Kex2 due to basic residues at P1' is affected by the
      type of residue in the P3 position. Some residues in P1' with large or bulky side
      chains yielded poor substrate specificity. The kcat/KM values for peptides with
      P2' substitutions containing Tyr in P3 were higher than those obtained for the
      peptides without Tyr. In fact, P' and P modifications mainly promoted changes in
      kcat and KM, respectively. The pH profile of Kex2 was fit to a double-sigmoidal
      pH-titration curve. The specificity results suggest that Kex2 might be involved
      in the processing of the putative cleavage sites in a polypeptide involved in
      cell elongation, hyphal formation and the processing of a toxin, which result in
      host cell lysis. In summary, the specificity of Kex2 is dependent on the set of
      interactions with prime and non-prime subsites, resulting in synergism.

PMID- 27720749
TI  - Personalized learning: From neurogenetics of behaviors to designing optimal
      language training.
AB  - Variability in drug responsivity has prompted the development of Personalized
      Medicine, which has shown great promise in utilizing genotypic information to
      develop safer and more effective drug regimens for patients. Similarly,
      individual variability in learning outcomes has puzzled researchers who seek to
      create optimal learning environments for students. "Personalized Learning" seeks
      to identify genetic, neural and behavioral predictors of individual differences
      in learning and aims to use predictors to help create optimal teaching paradigms.
      Evidence for Personalized Learning can be observed by connecting research in
      pharmacogenomics, cognitive genetics and behavioral experiments across domains of
      learning, which provides a framework for conducting empirical studies from the
      laboratory to the classroom and holds promise for addressing learning
      effectiveness in the individual learners. Evidence can also be seen in the
      subdomain of speech learning, thus providing initial support for the
      applicability of Personalized Learning to language.

PMID- 27720751
TI  - Effects of interface mutations on the dimerization of alanine glyoxylate
      aminotransferase and implications in the mistargeting of the pathogenic variants
      F152I and I244T.
AB  - In this work the dimerization process of the minor allelic form of human alanine
      glyoxylate aminotransferase, a pyridoxal 5'-phosphate enzyme, was investigated.
      Bioinformatic analyses followed by site-directed mutagenesis, size exclusion
      chromatography and catalytic activity experiments allowed us to identify Arg118,
      Phe238 and Phe240 as interfacial residues not essential for transaminase activity
      but important for dimer-monomer dissociation. The apo and the holo forms of the
      triple mutant R118A-Mi/F238S-Mi/F240S-Mi display a dimer-monomer equilibrium
      dissociation constant value at least ~260- and 31-fold larger, respectively, than
      the corresponding ones of AGT-Mi. In the presence of PLP, the apomonomer of the
      triple mutant undergoes a biphasic process: the fast phase represents the
      formation of an inactive PLP-bound monomer, while the slow phase depicts the
      monomer-monomer association that parallels the regain of transaminase activity.
      The latter events occur with a rate constant of ~0.02 MUM-1min-1. In the absence
      of PLP, the apomonomer is also able to dimerize but with a rate constant value
      ~2700-fold lower. Thereafter, the possible interference with the dimerization
      process of AGT-Mi exerted by the mutated residues in the I244T-Mi and F152I-Mi
      variants associated with Primary Hyperoxaluria type 1 was investigated by
      molecular dynamics simulations. On the basis of the present and previous studies,
      a model for the dimerization process of AGT-Mi, I244T-Mi and F152I-Mi, which
      outlines the structural defects responsible for the complete or partial
      mistargeting of the pathogenic variants, was proposed and discussed.

PMID- 27720752
TI  - In vivo induction of human chorionic gonadotropin by osmotic pump advances sexual
      maturation during pre-spawning phase in adult catfish.
AB  - Gonadal maturation is a critical event wherein gonads, under the influence of
      several hormones and factors, undergo cyclic morphological and physiological
      changes to produce functional gametes during the spawning phase. However,
      artificial induction can be effectively used to advance the maturation of gonad
      vis-a-vis spawning like behavior in seasonal breeders during the off-breeding
      season. In the present study, osmotic pumps loaded with 5000IU of human chorionic
      gonadotropin (hCG) or saline as control were implanted intraperitoneally for
      21days during the pre-spawning phase (May-June) in catfish Clarias batrachus and
      C. gariepinus. Significant increase in gonado-somatic index and sperm motility,
      and in the levels of certain sex steroids were observed in the hCG treated
      catfish when compared to control while estradiol-17beta (E2) was low.
      Histological analysis in hCG treated testis revealed densely packed sperm and/or
      spermatids inside the lumen wherein the control testis displayed normal
      characteristics of the pre-spawning phase. In females, histological analysis
      showed a significant increase in post-vitellogenic full-grown immature follicles
      as seen in the spawning phase. In accordance with this, the steroid hormone
      profile correlated well with steroidogenic shift from E2 to 17alpha,20beta-DP
      indicating oocyte maturation. However, in the control ovaries of C. batrachus,
      perinucleolar and pre-vitellogenic oocytes were seen to be predominant. In
      addition, when compared with the control, the hCG treated group displayed a
      significant increase in the transcripts of several genes associated with gonadal
      growth. Taken together, artificial induction by slow release of hCG is an
      effective strategy to advance sexual maturation in catfish in a programmed
      manner.

PMID- 27720753
TI  - Ovaprim, a commercial spawning inducer, stimulates gonadotropin subunit gene
      transcriptional activity: A study correlated with plasma steroid profile,
      ovulation and fertilization in the catfish Heteropneustes fossilis.
AB  - The commercial fish spawning inducer Ovaprim (OVP) containing a salmon
      gonadotropin-releasing hormone analogue and domperidone (a dopamine receptor-2
      antagonist) has been widely used as an effective spawning inducer in artificial
      breeding of fishes. It induces a preovulatory LH surge resulting in final oocyte
      maturation (FOM) and ovulation through a mechanism involving a steroidogenic
      shift to secrete a maturation-inducing steroid (MIS). In the present study, a
      0.5MUL/g body weight dose of OVP each injected at 0h and 24h intraperitoneally
      into gravid female catfish, Heteropneustes fossilis resulted in periovulatory
      changes in gonadotropin (GtH) subunit gene expression and steroid hormone levels.
      The OVP injections induced ovulation time-dependently from 6h onwards with 100%
      ovulation recorded from 24h to 48h. The fertilization rate was high from 6h to
      18h and declined from 24h onwards. The OVP treatment up regulated the expression
      of GtH subunit genes differentially. The expression of glycoprotein-alpha
      (GPalpha) and luteinizing hormone (LHbeta) peaked at 6h and 12h, and declined at
      18h and 24h after the first injection. The second OVP injection at 24h elicited
      only a transient increase in the GPalpha expression at 6h and a sustained
      increase in the LHbeta expression from 6h to 18h after the second injection, but
      both transcripts decreased subsequently. The follicle-stimulating hormone
      (FSHbeta) expression responded to the OVP treatment from 12h onwards and
      maintained a constant level from 18h to 36h after the first injection; the second
      dose had little effect. Plasma steroids were differentially altered: the levels
      of estradiol-17beta decreased while that of the MIS 17,20beta-dihydroxy-4-pregnen
      3-one; 17,20beta-DP increased, causing the steroidogenic shift preceding FOM and
      ovulation. The present results indicate that LHbeta expression coincides with the
      ovulation response and the late induction and maintenance of the FSH expression
      may be related to post-ovulatory events in the ovary.

PMID- 27720754
TI  - Physiological contribution of P2X receptors in postreceptoral signal processing
      in the mouse retina.
AB  - ATP activates P2X receptors and acts as a neurotransmitter in the nervous system.
      We have previously reported that P2X receptors modulate the firing rate of
      retinal ganglion cells. Since many subtypes of P2X receptors are distributed in
      the mouse retina, it is likely that the modulatory effects of P2X receptor
      mediated signaling can occur at multiple synaptic levels in the retina. In this
      study, we investigated whether P2X receptors expressed between the photoreceptor
      layer and the inner nuclear layer in the mouse retina were physiologically
      functional, by electroretinography (ERG). In the combined rod-cone ERG and the
      scotopic ERG, intravitreal injection of PPADS, an antagonist of P2X receptors,
      had no effects on the amplitude of the a-wave, but decreased the amplitude of the
      b-wave. In the photopic ERG, intravitreal injection of PPADS significantly
      decreased the amplitude of both the a-wave and the b-wave. In ex vivo recordings,
      a decrease in the b-wave amplitude was observed at 20MUM PPADS, confirming that
      the inhibition of the b-wave by intravitreal injection of PPADS is due to the
      inhibition of P2X receptors. Our findings suggest that P2X receptor-mediated
      signaling has a physiological effect in both the rod and the cone pathways in
      postreceptoral processing.

PMID- 27720755
TI  - Exploration in a dispersal task: Effects of early experience and correlation with
      other behaviors in prairie voles (Microtus ochrogaster).
AB  - Socially monogamous prairie voles (Microtus ochrogaster) display remarkable
      individual variation in social behaviors, which has been associated with
      differences in early life experience and neuropeptide receptor densities. These
      differences are also seen in the wild, where approximately 70% of young voles
      remain in their natal group as non-breeding alloparents, while the other 30%
      disperse. We investigated whether natural variation in early parental care could
      contribute to offspring's willingness to "disperse" (willingness to explore) in a
      laboratory context. Behavioral differences between dispersers and residents could
      also provide a way to interpret individual variation in other behaviors commonly
      observed under laboratory conditions. Breeder pairs ranked as high, medium or low
      contact, according to the amount of early parental care they provided to
      offspring, were used to produce and rear experimental subjects. Effects of early
      parental care on the offspring's willingness to disperse were seen at post-natal
      day 21, with high-contact offspring spending more time in the start cage and low
      contact offspring spending more time exploring. Variations in parental care were
      also associated with differences in juvenile and adult behaviors that could
      potentially encourage philopatry or dispersal behavior in the wild. High-contact
      offspring displayed less anxiety-like behavior compared to low-contact animals.
      Low-contact offspring displayed the lowest amount of alloparental care. High
      contact offspring spent more time in side-by-side contact with a potential
      partner compared to medium and low-contact offspring. These results suggest that
      variations in early parental care can impact weanlings' exploratory behavior, but
      that philopatry is not driven by high anxiety.

PMID- 27720756
TI  - Behavioural responses of Pacific salmon to chemical disturbance cues during the
      spawning migration.
AB  - Many fish that are exposed to a threat release disturbance cues, which are
      chemicals that alert conspecifics to the presence of the threat. The release of
      disturbance cues has been well demonstrated in various species of laboratory
      reared fish. Migratory fish species often exhibit increased cortisol levels and
      are exposed to numerous stressors during their migrations, which could trigger
      the release of disturbance cues. We tested the responses of wild migrating
      sockeye salmon (Oncorhynchus nerka) and pink salmon (O. gorbuscha) to the odours
      of disturbed and undisturbed conspecifics to determine whether these fish release
      disturbance cues following exposure to a simulated stressor. Furthermore, we
      tested the responses of sockeye salmon to water-borne cortisol, following
      evidence from past studies that this chemical is excreted through the gills of
      stressed fish, and speculation that endogenous correlates of stress might
      function as disturbance cues. We found that sockeye salmon avoid the odour of
      disturbed conspecifics, whereas pink salmon do not. Avoidance occurred in both
      female and male sockeye salmon, and was associated with an increase in plasma
      cortisol levels in females, but not in males. We also found no behavioural
      response to water-borne cortisol, which suggests this chemical does not act as an
      exogenous disturbance cue in sockeye salmon. Avoidance of disturbed conspecifics
      could limit exposure to risks during the sockeye salmon spawning migration, but
      could also delay the rate of migration and thereby accrue reproductive costs.

PMID- 27720757
TI  - Comprehensive analysis of alpha 2-3-linked sialic acid specific Maackia amurensis
      leukagglutinin reveals differentially occupied N-glycans and C-terminal
      processing.
AB  - Seeds of Maackia amurensis constitutes two sialic acid specific agglutinins known
      as leukagglutinin and hemagglutinin. Maackia amurensis leukagglutinin (MAL)
      recognizes alpha2-3-linked sialic acid present mainly in N-glycans and composed
      of two disulfide linked monomers. It exhibits potential N-glycosylation sites
      (four PNGs) which have been assumed to undergo differential occupancy. In this
      study we have characterized the site specific macro- and microheterogeneity of
      monomers in detail by analysing N-glycopeptides and peptides through liquid
      chromatography coupled to ion trap mass spectrometer in MS3 mode (LC-MSn). We
      observed the presence of mainly paucimannose N-glycans at Asn61, Asn113 and
      Asn191 whereas a high mannose type with varying Man5-9 occurs at Asn179.
      Interestingly Asn179 and Asn191 exhibited differential occupancy which was
      evident by the presence of non-glycosylated peptides. This has contributed to the
      difference in molecular mass of monomers upon SDS-PAGE. Further the presence of
      disulfide linked peptides confirmed the covalent linkage of monomers which also
      undergoes uniform C-terminal processing.

PMID- 27720758
TI  - Characterization of a novel protease from Aeribacillus pallidus strain VP3 with
      potential biotechnological interest.
AB  - The present study investigates the purification and physico-chemical
      characterization of an extracellular protease from the Aeribacillus pallidus
      strain VP3 previously isolated from a geothermal oil-field (Sfax, Tunisia). The
      maximum protease activity recorded after 22h of incubation at 45 degrees C was
      3000U/ml. Pure enzyme, designated as SPVP, was obtained after ammonium sulfate
      fractionation (40-60%)-dialysis followed by heat-treatment (70 degrees C for
      30min) and UNO Q-6 FPLC anion-exchange chromatography. The purified enzyme is a
      monomer of molecular mass about 29kDa. The sequence of the 25 NH2-terminal
      residues of SPVP showed a high homology with those of Bacillus proteases. The
      almost complete inhibition by PMSF and DIFP confirmed that SPVP is a member of
      serine protease family. Its optima of pH and temperature were pH 10 and 60
      degrees C, respectively. Its half-life times at 70 and 80 degrees C were 8 and
      4h, respectively. Its catalytic efficiency was higher than those of SAPCG,
      Alcalase Ultra 2.5L, and Thermolysin type X. SPVP exhibited excellent stability
      to detergents and wash performance analysis revealed that it could remove blood
      stains effectively and high resistance against organic solvents. These properties
      make SPVP a potential candidate for applications in detergent formulations and
      non-aqueous peptide biocatalysis.

PMID- 27720759
TI  - Multiple Functional Variants of IFIH1, a Gene Involved in Triggering Innate
      Immune Responses, Protect against Vitiligo.

PMID- 27720761
TI  - The cutaneous secretion of the casque-headed tree frog Corythomantis greeningi:
      Biochemical characterization and some biological effects.
AB  - Corythomantis greeningi is a tree-frog endemic of the Brazilian semi-arid
      (Caatinga), mainly characterized by the flat, mineralized and spiny head, which
      is associated with phragmotic habits. It is already known that the skin secretion
      of this amphibian from both head and body is quite toxic and is used as an
      efficient chemical defence against predators. However, the biochemical
      characteristics and pharmacological effects of this secretion are still very
      little studied. We have tested the crude skin secretion, as well as the ten major
      fractions obtained by RP-HPLC for nociceptive and edema activity and for in vitro
      cytotoxicity using murine models. SDS-PAGE analyses demonstrated that the
      majority of proteins ranging through the gel lie between 55 and 30 kDa. LC-MS
      analysis showed multiple low molecular mass molecules (200-500 Da), which are
      consistent with masses of alkaloids and steroids. The crude skin secretion was
      able to induce fast and persistent edema accompanied by intense dose-dependent
      nociception. From the 10 tested fractions, five induced both edema and
      nociception, six fractions were able to induce only edema (80-170% control), and
      seven fractions induced only nociception (15-30 times compared to control). In
      addition, inhibition of cell growth (IC50) was demonstrated in murine fibroblasts
      and melanoma cells. From the data obtained, we confirmed that the skin secretion
      of C. greeningi is very toxic and is rich in compounds able to directly provoke
      local inflammation and nociception. Such characteristics are important as part of
      the chemical defensive repertory of this species.

PMID- 27720762
TI  - Pharmacological analysis of hemodynamic responses to Lachesis muta (South
      American bushmaster) snake venom in anesthetized rats.
AB  - In this work, we examined some mechanisms involved in the hypotension caused by
      Lachesis muta (South American bushmaster) venom in anesthetized rats. Venom (1.5
      mg/kg, i.v.) caused immediate hypotension that was maximal after 5 min and
      gradually returned to baseline over 60 min. Pretreatment of rats with the non
      selective nitric oxide synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl
      ester (L-NAME) did not attenuate the early phase of venom-induced hypotension,
      but abolished the recovery phase and resulted in rapid death; a similar effect
      was observed with the soluble guanylate cyclase (sGC) inhibitor ODQ. In contrast,
      the hemodynamic responses to venom were not attenuated by the non-selective NOS
      inhibitor NG-monomethyl-L-arginine, the inducible NOS inhibitor aminoguanidine,
      the phosphodiesterase 5 inhibitor sildenafil, the adenylate cyclase (AC)
      inhibitor SQ-22.536, the non-selective muscarinic receptor antagonist atropine,
      the bradykinin B2 receptor antagonist HOE-140 and the non-selective
      cyclooxygenase inhibitor indomethacin. Preincubation of venom with the PLA2
      inhibitor pBPB had no effect on the immediate hypotension but tended to improve
      the recovery phase. Neither AEBSF (a serine proteinase inhibitor) nor EDTA (a
      metalloproteinase inhibitor) prevented the venom-induced hypotension, but AEBSF
      and not EDTA protected against the lethality of a high dose (3.0 mg/kg, i.v.).
      There were no marked changes in the ECG parameters with the various treatments,
      except with L-NAME and ODQ that increased the RR interval. Pulmonary thrombus
      formation was markedly enhanced by L-NAME and ODQ, and to a lesser extent by
      pBPB, especially in small vessels, whereas AEBSF and EDTA inhibited thrombus
      formation. Venom relaxed phenylephrine-precontracted thoracic aorta and pulmonary
      artery in vitro, with the latter being more sensitive. The relaxation was
      endothelium-dependent and was inhibited by ODQ but not by H-89, a protein kinase
      A (PKA) inhibitor. Together, these findings indicate involvement of the
      NO/sGC/cGMP, but not the AC/cAMP/PKA signaling pathway, in the hemodynamic
      responses to L. muta venom in rats. Muscarinic mechanisms, kinins and arachidonic
      acid metabolites are apparently not involved.

PMID- 27720760
TI  - Trim32 Deficiency Enhances Th2 Immunity and Predisposes to Features of Atopic
      Dermatitis.
AB  - Altered innate immunity is a feature of certain skin inflammatory diseases such
      as psoriasis and atopic dermatitis (AD). In this study, we provide evidence that
      deficiency in Trim32 (a tripartite motif [TRIM] protein with innate antiviral
      activity) contributes to a T helper type 2 biased response and predisposes to
      features of AD in mice. On treatment with the toll-like receptor 7 agonist
      imquimod (IMQ), Trim32 knockout mice displayed compromised psoriasiform
      phenotypes and defective T helper type 17 response. Instead, IMQ treatment of
      Trim32 knockout mice induced AD-like phenotypes with enhanced skin infiltration
      of eosinophils and mast cells, elevation of T helper type 2 cytokines/chemokines
      expression, and reduced expression of filaggrin protein expression. Furthermore,
      although the induction of phosphorylated Stat3 and RelA was compromised after IMQ
      treatment in the knockout mice, phosphorylated Stat6 was elevated. CC chemokine
      ligand 20 induction by tumor necrosis factor-alpha and IL-17A was reduced in
      Trim32-deficient keratinocytes, whereas CC chemokine ligand 5 induction by tumor
      necrosis factor-alpha and IL-4 was enhanced. In addition, Trim32 protein levels
      were elevated in mice treated with IMQ. Unlike Trim32 overexpression in
      psoriasis, TRIM32 levels were low in patients with AD. Based on Trim32 induction
      by IMQ, the lower levels of TRIM32 in AD skin compared with healthy control and
      psoriatic skin suggest a defective TRIM32 pathway in AD pathogenesis.

PMID- 27720763
TI  - Hemodynamic responses to Lachesis muta (South American bushmaster) snake venom in
      anesthetized rats.
AB  - In this work, we examined the hemodynamic responses to Lachesis muta (South
      American bushmaster) venom in anesthetized male Wistar rats. Venom (1.5 mg/kg,
      i.v.) caused immediate hypotension that was followed by a gradual return towards
      baseline over 60 min; there were no significant changes in heart rate, ECG
      parameters and respiratory rate. A higher dose (3 mg/kg, i.v.) caused sustained
      hypotension, variable bradycardia, respiratory depression and fluctuations in
      ECG; death occurred within 10-60 min. Venom injected intramuscularly (15 mg/kg)
      produced a smaller decrease in blood pressure that was more persistent than with
      1.5 mg/kg (i.v.). Pre-treatment with atenolol (selective beta1-adrenergic
      receptor antagonist) potentiated the response to venom (1.5 mg/kg, i.v.) and
      resulted in a hemodynamic profile similar to that seen with 3 mg/kg (i.v.).
      Macroscopically, systemic hemorrhage was seen only in the ileum, whereas
      histological analysis revealed extensive pulmonary hemorrhage; the heart, liver
      and kidney were generally unaffected. Intravascular pulmonary thrombosis occurred
      with venom given i.v. and i.m., but was less marked with the latter route. In rat
      isolated perfused hearts, venom caused a persistent decrease in left ventricular
      developed pressure but no change in heart rate, coronary flow or ECG; there was
      tissue necrosis and release of CK-MB that were abolished by pre-treating venom
      with the PLA2 inhibitor p-bromophenacyl bromide. These results show that in rats
      L. muta venom causes hypotension, bradycardia and respiratory depression,
      depending on the dose and route of administration. The hemodynamic responses
      apparently do not involve direct cardiotoxicity and are modulated by the
      adrenergic system.

PMID- 27720764
TI  - Activity correlations between on-like and off-like cells of the rostral
      ventromedial medulla and simultaneously recorded wide-dynamic-range neurons of
      the spinal dorsal horn in rats.
AB  - Considerable evidence supports the notion that on- and off-cells of the rostral
      ventromedial medulla (RVM) facilitate and depress, respectively, spinal
      nociceptive transmission. This notion stems from a covariation of on- or off-cell
      activities and spinal nocifensive reflexes. Such covariation could theoretically
      be due to their independently responding to a common source, or to an RVM-derived
      modulation of ventral horn neurons. Here, we tested whether on- and off-cells
      indeed modulate spinal nociceptive neurons. In deeply anesthetized rats, unitary
      recordings were simultaneously made from an RVM on-like or off-like cell and a
      spinal nociceptive neuron that shared a receptive field (RF) at a hind paw.
      Action potential firing in RVM/spinal neuron pairs was highly correlated,
      positively for on-like cells and negatively for off-like cells, both during
      ongoing activity and during application of calibrated noxious pressure to the RF.
      Microinjection of morphine into RVM induced a correlated decrease in on-like
      cell/spinal neuron ongoing activity and response to noxious stimulation. RVM
      morphine induced changes in off-like cell activity that were not correlated with
      spinal neuronal activity. These results suggest that on-cells exert a positive
      modulation upon spinal nociceptive neurons, upstream to ventral horn circuits and
      plausibly at the origin of nociceptive information that eventually reaches the
      cerebral cortex. On-cells may in this manner contribute to inflammation- and
      neuropathy-induced increases in withdrawal reflexes. Most significantly, on-cell
      modulation of nociceptive neurons may be a key factor in clinical pain conditions
      such as hyperalgesia and allodynia.

PMID- 27720765
TI  - Induced Neural Differentiation of MMP-2 Cleaved (RADA)4 Drug Delivery Systems.
AB  - (RADA)4 self-assembling peptides (SAPs) are promising for neural nanoscaffolds
      with on-demand drug delivery capabilities due to their automated synthesis, in
      situ assembly, and potential for interaction with and release of biomolecules.
      Neuroinflammation cued on-demand drug release, due to up-regulated proteases, may
      well be vital in the treatment of several neurological diseases. In these
      conditions, releasing neurotrophic growth factors (NTFs) could potentially lead
      to neuroprotection and neurogenesis. As such, (RADA)4 was made with the high and
      low activity matrix metalloproteinase 2 (MMP-2) cleaved sequences, GPQG+IASQ
      (CP1) and GPQG+PAGQ (CP2), the brain-derived NTF secretion stimulating peptide
      MVG (DP1) and the ciliary NTF analogue DGGL (DP2). PC-12 cell culture was
      performed to assess bioactive substrate cell adhesion and NTF specific neuronal
      differentiation. The laminin-derived IKVAV peptide, known for neural cell
      attachment and interaction, was tethered to (RADA)4-IKVAV and mixed in increasing
      increments with (RADA)4 for this purpose. With 1 nanomolar MMP-2 treatment,
      product formation was observed to increase over a three day period, with
      (RADA)4/(RADA)4-CP1/CP2 mixture, however there was little difference between
      groups. Smaller CP1/CP2 concentrations displayed comparable (RADA)4 nanoscale
      morphology to higher concentrations. Acetylcholine esterase and neural
      differentiation was observed over 3 days with 1 nM MMP-2 treatment according to
      the following makeup: 8/1/1 (RADA)4/(RADA)4-IKVAV/(RADA)4-CP1/CP2-DP1/DP2.
      Signalling gradually increased in all groups, and neurite outgrowth was visible
      after three days.

PMID- 27720766
TI  - Metformin: An anti-diabetic drug to fight cancer.
AB  - Since epidemiologic data have highlighted the positive effects of metformin to
      reduce cancer incidence and mortality, many in vitro and in vivo studies as well
      as a large number of clinical trials have been conducted in order to study its
      potential. The many anticancer actions of metformin lead to a cytostatic effect.
      Two distinct but not exclusive mechanisms can be implicated in these actions.
      First, by decreasing insulinemia and glycaemia, metformin can block the PI3K/MAPK
      signalling pathway implicated in cell growth. Second, metformin can directly act
      on cancer cells by targeting various pathways including tumour metabolism,
      inflammation, angiogenesis or cancer stem cells, mainly through the activation of
      the AMPK pathway. Nonetheless, although metformin alone displays chemopreventive
      properties, it does not seem to be sufficient to treat cancer, raising the need
      to be combined with other drugs (e.g. chemotherapy or glycolysis inhibitors) in
      order to synergistically reveal its cytotoxic action. However, in particular
      conditions such as specific mutations (e.g. LKB, p53 or OCT1) or low glucose
      availability, metformin alone does have cytotoxic effects. Thus, it is essential
      to consider the associated biomarkers in order to determine the potential of
      metformin in different types of cancers.

PMID- 27720767
TI  - Eyes on systems pharmacology.

PMID- 27720768
TI  - Application of immuno-PCR assay for the detection of serum IgE specific to
      Bermuda allergen.
AB  - In vivo and in vitro tests are the two major ways of identifying the triggering
      allergens in sensitized individuals with allergic symptoms. Both methods are
      equally significant in terms of sensitivity and specificity. However, in certain
      circumstances, in vitro methods are highly preferred because they circumvent the
      use of sensitizing drugs in patients. In current study, we described a highly
      sensitive immuno-PCR (iPCR) assay for serum IgE specific to Bermuda allergens.
      Using oligonucleotide-labelled antibody, we used iPCR for the sensitive detection
      of serum IgE. The nucleotide sequence was amplified using conventional PCR and
      the bands were visualized on 2.5% agarose gel. Results demonstrated a 100-fold
      enhancement in sensitivity of iPCR over commercially available enzyme-linked
      immunosorbent assay (ELISA) kit. Our iPCR method was highly sensitive for Bermuda
      specific serum IgE and could be beneficial in allergy clinics.

PMID- 27720770
TI  - Transurethral Resection Alone Vs Resection Combined With Therapeutic
      Hydrodistention as Treatment for Ulcerative Interstitial Cystitis: Initial
      Experience With Propensity Score Matching Studies.
AB  - OBJECTIVE: To compare the therapeutic efficacy of transurethral resection (TUR)
      alone with that of TUR combined with therapeutic hydrodistention in patients with
      ulcerative interstitial cystitis (IC). METHODS: The study subjects were 44 female
      patients newly diagnosed with IC who underwent TUR to treat ulcerative IC and who
      were available for follow-up, without recurrence of disease for 12 months. We
      retrospectively studied both patients who underwent TUR alone (group I) and those
      who underwent TUR combined with therapeutic hydrodistention (group II).
      Improvements in pain and voiding symptoms were retrospectively evaluated using a
      10-point visual analog scale for pain and a 3-day micturition chart. RESULTS:
      Group I included 22 patients and group II included 22 patients of mean ages 58.45
      +/- 11.01 and 56.27 +/- 11.86 years, respectively. Use of a 10-point visual
      analog scale showed that pain decreased after the procedures in both groups, but
      the improvement did not differ between groups. The maximum functional bladder
      capacities of patients in group I were 161.36, 192.47, and 204.12 mL,
      respectively, before, at 6 months, and at 12 months after the operation; the
      maximum functional bladder capacities of patients in group II were 175.45,
      263.14, and 291.17 mL, respectively. The voiding frequencies of group I were
      12.59, 10.67, and 9.89 times daily, respectively, before, at 6 months, and at 12
      months after the operation; the voiding frequencies of group II were 12.95, 9.5,
      and 8.29 times daily, respectively. CONCLUSION: TUR combined with therapeutic
      hydrodistention increased bladder capacity and improved voiding symptoms more so
      than did TUR alone for ulcerative IC.

PMID- 27720771
TI  - Giant Pheochromocytoma With Leukemoid Reaction: A Case Report.
AB  - We present a rare case of silent giant pheochromocytoma with leukemoid reaction
      that has not been reported before. The patient was a 61-year-old woman who
      complained of progressive weight loss for 3 months. Preoperatively the urine
      vanillylmandelic acid was 105.54 mg/24 hours. White blood cell count was 56.9 *
      109/L. Abdominal ultrasound and computed tomography revealed a mass measuring 18
      * 11 cm in the left adrenal area. The patient underwent adrenal gland neoplasm
      resection. Postoperative histopathologic evaluation confirmed the diagnosis of
      pheochromocytoma. The leukocyte dropped to normal gradually in 10 days after the
      operation. Giant pheochromocytoma with leukemoid reaction was very rare.
      Resection is the only curative treatment.

PMID- 27720769
TI  - Fear conditioning selectively disrupts noradrenergic facilitation of GABAergic
      inhibition in the basolateral amygdala.
AB  - Inappropriate fear memory formation is symptomatic of many psychopathologies, and
      delineating the neurobiology of non-pathological fear learning may provide
      critical insight into treating these disorders. Fear memory formation is
      associated with decreased inhibitory signaling in the basolateral amygdala (BLA),
      and disrupted noradrenergic signaling may contribute to this decrease. BLA
      noradrenergic neurotransmission has been implicated in fear memory formation, and
      distinct adrenoreceptor (AR) subtypes modulate excitatory and inhibitory
      neurotransmission in this region. For example, alpha1-ARs promote GABA release
      from local inhibitory interneurons, while beta3-ARs potentiate neurotransmission
      at lateral paracapsular (LPC) GABAergic synapses. Conversely, beta1/2-ARs amplify
      excitatory signaling at glutamatergic synapses in the BLA. As increased BLA
      excitability promotes fear memory formation, we hypothesized that fear learning
      shifts the balanced regional effects of noradrenergic signaling toward
      excitation. To test this hypothesis, we used the fear-potentiated startle
      paradigm in combination with whole cell patch clamp electrophysiology to examine
      the effects of AR activation on BLA synaptic transmission following fear
      conditioning in male Long-Evans rats. We first demonstrated that inhibitory
      neurotransmission is decreased at both local and LPC synapses following fear
      conditioning. We next measured noradrenergic facilitation of BLA inhibitory
      signaling at local and LPC synapses using alpha1-and beta3-AR agonists (1 MUM
      A61603 and 10 MUM BRL37344), and found that the ability of these agents to
      facilitate inhibitory neurotransmission is disrupted following fear conditioning.
      Conversely, we found that fear learning does not disrupt noradrenergic modulation
      of glutamatergic signaling via a beta1/2-AR agonist (1 MUM isoproterenol). Taken
      together, these studies suggest that fear learning increases BLA excitability by
      selectively disrupting the inhibitory effects of noradrenaline.

PMID- 27720772
TI  - Sustained-release Formulation of Mitomycin C to the Upper Urinary Tract Using a
      Thermosensitive Polymer: A Preclinical Study.
AB  - OBJECTIVE: To evaluate the safety and feasibility of single and serial
      instillations of MitoGel into the upper urinary tract using a preclinical swine
      animal model. MitoGel is a novel sustained release formulation of mitomycin C
      (MMC) based on RTGel, a proprietary thermosensitive hydrogel technology. MitoGel
      is liquid at cold temperatures and solidifies to gel state at body temperature.
      It is intended as a treatment for upper tract urothelial carcinoma, given its
      ability to provide sustained release of MMC in the upper urinary tract. MATERIALS
      AND METHODS: We utilized 23 pigs in a 3-phase design. All animals underwent
      bilateral nephrostomy tube placement. During phase 1, 3 animals underwent
      antegrade RTGel instillation, imaging, and euthanasia within 12 hours. In phase
      2, 10 pigs underwent single antegrade instillation, unilateral nephrectomy 3 days
      following instillation, and contralateral nephrectomy and euthanasia 30 days
      following instillation. During phase 3, 10 animals underwent 6 instillations over
      3 weeks, followed by bilateral nephrectomy and necropsy 30 days postinstillation.
      MitoGel (2 mg/mL and 4 mg/mL), aqueous MMC (2 mg/mL and 4 mg/mL), and RTGel alone
      were evaluated. RESULTS: MitoGel remained visible within the pelvicalyceal system
      on fluoroscopic and computed tomography imaging for 4-6 hours. MMC plasma levels
      were well within acceptable safety thresholds. There was no evidence of urinary
      obstruction, acute kidney injury, sepsis, or myelosuppression. Histologic changes
      in the urinary system were mild and transient. CONCLUSION: Antegrade MitoGel
      delivery to the pelvicalyceal system of Yorkshire swine is feasible and safe.
      Further evaluation of MitoGel in human clinical trials is warranted.

PMID- 27720773
TI  - Long-term Impacts of Concurrent Posterior Urethral Valve Ablation and Bladder
      Neck Incision on Urinary Continence and Ejaculation.
AB  - OBJECTIVE: To assess the long-term impacts of bladder neck incision (BNI) on
      continence and ejaculatory function of adults who underwent concurrent posterior
      urethral valve (PUV) ablation and BNI during childhood. MATERIALS AND METHODS: A
      retrospective chart review was performed to find all adult patients with relevant
      history. All patients had undergone BNI at 6 o'clock proximal to the verumontanum
      with caution to leave the adventitia and verumontanum untouched. Charts were
      reviewed and attempts were made to contact those >=18 years old for follow-up.
      Patients were specifically evaluated for lower urinary tract symptoms and
      ejaculatory condition. RESULTS: Among patients treated for PUV between 1998 and
      2015 in our center, 21 were >=18 years old at the time of assessment. Until
      February 2016, we were able to contact 18 patients, all of whom agreed to
      participate. Mean age was 21.1 +/- 2.9 years with a mean follow-up of 12.5 +/-
      4.8 years. None of those contacted had incontinence or dry ejaculations. All
      considered their ejaculations normal and only one complained of weak
      ejaculations. Four of 5 patients who consented to perform a semen analysis had
      normal tests and 1 had low sperm count with abnormal motility. CONCLUSION: BNI is
      not associated with additional risk of incontinence and dry ejaculation in early
      adulthood and preserves antegrade ejaculation. Concomitant valve ablation with
      BNI may provide additional benefits in care of PUV children, especially those
      with prominent bladder neck and poor bladder function at presentation.

PMID- 27720775
TI  - The Effect of Anticoagulation on Bleeding-related Complications Following
      Ureteroscopy.
AB  - OBJECTIVE: To analyze bleeding-related complications among patients on long-term
      anticoagulation (AC) undergoing ureteroscopy (URS). Current American Urological
      Association/International Consultation on Urological Diseases guidelines state
      that it is safe to continue AC in routine URS; however, these recommendations are
      based on small case series. PATIENTS AND METHODS: There were 4799 identified URS
      procedures performed at our institution between June 2009 and February 2016.
      Records were then retrospectively reviewed to confirm AC use and identify
      periprocedural complications. Anticoagulant agents evaluated included warfarin,
      enoxaparin, and non-vitamin K antagonists (ie, rivaroxaban, dabigatran,
      apibaxan). Patients were excluded if they were taking a concurrent antiplatelet
      (AP) agent or if additional non-URS procedures were performed. RESULTS: Of the
      4799 URS procedures, 272 (5.6%) were done on patients taking chronic AC. Of
      these, 193 (71%) held AC, 53 (19%) were bridged with enoxaparin, and 26 (10%)
      continued AC. The median age was 70.2 years and the majority of patients (64.2%)
      underwent a stone procedure with a stone-free rate of 73%. The overall bleeding
      related complication rate was 8.1% whereas the significant bleeding-related event
      rate was 5.9%. Patients continuing AC had the highest significant bleeding
      related event rate at 15.4% compared to 9% and 3% for those bridged with
      enoxaparin and those who held, respectively (P = .01). CONCLUSION: Continuation
      or bridging of AC may increase the risk of perioperative bleeding. The risks and
      benefits of proceeding with URS on AC must be weighed carefully. Pending external
      validation, this information may be used for patient counseling and risk
      stratification.

PMID- 27720774
TI  - Outcomes and Prognostic Factors of Primary Urethral Cancer.
AB  - OBJECTIVE: To identify prognostic and treatment factors for primary urethral
      cancer using a nationwide database. MATERIALS AND METHODS: The National Cancer
      Database was queried for all cases of primary urethral cancer from 2004 to 2013.
      Patients with other cancer diagnoses, metastasis, or diagnosis on autopsy were
      excluded. Proportional hazards regression was used to identify independent
      predictors of overall survival in patients with primary urethral cancer. Because
      we hypothesized that predictors may covary by sex, we also performed regression
      analysis stratified by sex. RESULTS: We identified 1268 men and 869 women with
      primary urethral cancer. Women tended to have more advanced tumors and
      adenocarcinoma histology. Median survival for the entire cohort was 49 months (43
      55), with 5- and 10-year survival rates of 46% and 31%, respectively. On
      multivariate analysis, age, race, stage, grade, and Charlson comorbidity index
      were independent predictors of overall survival. Histology was not a predictor of
      overall survival in the combined model; however, adenocarcinoma in women
      increased hazards of death, whereas it decreased hazards of death in men when
      compared with squamous cell carcinoma. CONCLUSION: Men and women with primary
      urethral cancer had significant differences in histology, grade, and nodal
      status. In addition to several expected disease-related factors, black race was
      associated with increased mortality for patients with primary urethral cancer.

PMID- 27720776
TI  - X-ray-free Ultrasound-guided Percutaneous Nephrolithotomy: How to Select the
      Right Patient?
AB  - OBJECTIVE: To identify factors associated with successful ultrasound guidance for
      each surgical step of ultrasound-guided percutaneous nephrolithotomy (PCNL).
      PATIENTS AND METHODS: Consecutive patients undergoing PCNL between March 2015 and
      June 2016 were prospectively enrolled. An attempt was made to use ultrasound
      guidance in renal access, tract dilation, and nephrostomy tube placement for each
      patient. For steps during which ultrasound guidance was unsuccessful,
      fluoroscopic screening was applied. Regression analysis identified patient
      characteristics associated with successful use of ultrasound guidance. RESULTS: A
      total of 96 patients composed this cohort, with a mean body mass index of 28.7
      kg/m2. Mean stone size was 33.1 +/- 18.9 mm, and no hydronephrosis was found in
      63.5% of cases. Fluoroscopic screening was required for renal access in 27 cases
      (28.1%), tract dilation in 38 (39.6%), and nephrostomy tube placement in 80
      (83.3%). Multivariate analysis demonstrated that successful ultrasound guidance
      was significantly associated with the presence of hydronephrosis for renal access
      and the absence of staghorn calculi for tract dilation. Ultrasound-guided
      nephrostomy tube placement appeared linked to surgeon experience. CONCLUSION: To
      achieve completely x-ray-free ultrasound-guided PCNL, the ideal patient should
      have a hydronephrotic collecting system with no staghorn stone present. For
      practitioners looking to adopt ultrasound guidance into their PCNL practice,
      these represent the most appropriate patients to safely initiate a surgical
      experience.

PMID- 27720777
TI  - Complementary and Conventional Health-care Utilization Among Young Australian
      Women With Urinary Incontinence.
AB  - OBJECTIVE: To examine the relationship between health status and health service
      utilization (including conventional and complementary and alternative medicine
      [CAM]) accessed by women experiencing urinary incontinence (UI). Although a high
      number of younger women report symptoms of UI, such as leaking urine, only a
      small proportion seek help for these symptoms. MATERIALS AND METHODS: The
      Australian Longitudinal Study on Women's Health is a large nationally
      representative study that investigates the health and well-being of women. The 2
      most recent surveys (2006 and 2009) of the young cohort (women aged 28-33 and 31
      36 respectively) were analyzed. RESULTS: The presence of UI was 8.5% in 2006 (n =
      859) and 23.3% in 2009 (n = 1878), whereas the percentage of women who sought
      help for their UI was 18.6% (n = 160) and 2.2% (n = 182) respectively. Women with
      UI had poorer health compared with women without UI (P < .005), and women who
      sought help for their symptoms had poorer physical functioning than women who did
      not (P < .005). Women who sought help were greater users of conventional and CAM
      health services (P < .005), including a general practitioner, specialist,
      hospital doctor, physiotherapist, and naturopath. CONCLUSION: UI is relatively
      common in younger women. However, many do not seek help. Of the women who do seek
      care, a large number visit CAM professionals as well as conventional medical
      professionals, despite a lack of research evaluating the efficacy of CAM
      treatment. Research is needed to explore CAM practitioner approaches to the
      treatment of UI and to evaluate the efficacy of these treatments.

PMID- 27720778
TI  - PBA2, a novel inhibitor of imatinib-resistant BCR-ABL T315I mutation in chronic
      myeloid leukemia.
AB  - Chronic Myeloid Leukemia (CML) is largely caused by the Philadelphia (Ph)
      chromosome carrying the Break point Cluster Region-Abelson (BCR-ABL) oncogene.
      Imatinib is a BCR-ABL-targeted therapy and considered the standard of care in CML
      management. Resistance to imatinib therapy often develops because of mutations in
      the BCR-ABL kinase domain. In this study, we evaluated PBA2, a novel BCR-ABL
      inhibitor, for its anti-cancer activity against BCR-ABL expressing BaF3 cells.
      PBA2 shows potent activity against wild-type and T315I mutated BaF3 cells as
      compared with imatinib. PBA2 inhibited the phosphorylation of BCR-ABL and its
      downstream signaling in BaF3/WT and BaF3/T315I cells. PBA2 inhibited the mRNA
      expression of BCR-ABL in BaF3/WT and BaF3/T315I cells. Mechanistically, PBA2
      increased the cell population in sub G1 phase of the cell cycle, induced
      apoptosis and elevated ROS production in both BaF3/WT and BaF3/T315I cells. Taken
      together, our results indicate that PBA2 exhibits anti-proliferative effects and
      inhibits the imatinib-resistant T315I BCR-ABL mutation. PBA2 may be a novel drug
      candidate for overcoming the resistance to imatinib in CML patients.

PMID- 27720779
TI  - Riboflavin, MTHFR genotype and blood pressure: A personalized approach to
      prevention and treatment of hypertension.
AB  - Hypertension is the leading risk factor contributing to mortality worldwide,
      primarily from cardiovascular disease (CVD), while effective treatment of
      hypertension is proven to reduce CVD events. Along with the well recognized
      nutrition and lifestyle determinants, genetic factors are implicated in the
      development and progression of hypertension. In recent years genome-wide
      association studies have identified a region near the gene encoding the folate
      metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) among eight loci
      associated with blood pressure. Epidemiological studies, which provide a separate
      line of evidence to link this gene with blood pressure, show that the 677C->T
      polymorphism in MTHFR increases the risk of hypertension by 24-87% and CVD by up
      to 40%, albeit with a large geographical variation in the extent of excess
      disease risk suggestive of a gene-environment interaction. Emerging evidence
      indicates that the relevant environmental factor may be riboflavin, the MTHFR co
      factor, via a novel and genotype-specific effect on blood pressure. Randomized
      trials conducted in hypertensive patients (with and without overt CVD) pre
      screened for this polymorphism show that targeted riboflavin supplementation in
      homozygous individuals (MTHFR 677TT genotype) lowers systolic blood pressure by 6
      to 13 mmHg, independently of the effect of antihypertensive drugs. The latest
      evidence, that the blood pressure phenotype associated with this polymorphism is
      modifiable by riboflavin, has important clinical and public health implications.
      For hypertensive patients, riboflavin supplementation can offer a non-drug
      treatment to effectively lower blood pressure in those identified with the MTHFR
      677TT genotype. For sub-populations worldwide with this genotype, better
      riboflavin status may prevent or delay the development of high blood pressure.
      Thus riboflavin, targeted at those homozygous for a common polymorphism in MTHFR,
      may offer a personalized treatment or preventative strategy for hypertension.
      Further investigations of this novel gene-nutrient interaction in relation to
      blood pressure, hypertension and hypertension in pregnancy are required.

PMID- 27720780
TI  - Epigenetics in fibrosis.
AB  - Fibrosis is a common and important disease. It is a pathological state due to
      excessive scar formation mediated by an increase in activated fibroblasts that
      express alpha smooth muscle actin and copious amounts of extracellular matrix
      molecules. Epigenetics is an area of research that encompasses three main
      mechanisms: methylation, histone modifications to the tails of histones and also
      non-coding RNAs including long and short non-coding RNAs. These three mechanisms
      all seek to regulate gene expression without a change in the underlying DNA
      sequence. In recent years an explosion of research, aided by deep sequencing
      technology becoming available, has demonstrated a role for epigenetics in
      fibrosis, either organ specific like lung fibrosis or more widespread as in
      systemic sclerosis. While the great majority of epigenetic work in fibrosis is
      centered on histone codes, more recently the non-coding RNAs have been examined
      in greater detail. It is known that one modification can affect the other and
      cross-talk among all three adds a new layer of complexity. This review aims to
      examine the role of epigenetics in fibrosis, evaluating all three mechanisms, and
      to suggest possible areas where epigenetics could be targeted therapeutically.

PMID- 27720781
TI  - Failed Primary Bladder Exstrophy Closure with Osteotomy: Multivariable Analysis
      of a 25-Year Experience.
AB  - PURPOSE: Successful primary bladder exstrophy closure provides the best
      opportunity for patients to achieve a functional closure and urinary continence
      regardless of the method of repair. Use of osteotomy during initial closure has
      significantly improved success rates. However, failures can still occur. We
      identify factors that contribute to a failed primary exstrophy closure with
      osteotomy. MATERIALS AND METHODS: We reviewed a prospectively maintained
      institutional database for classic bladder exstrophy cases primarily closed with
      osteotomy at our institution or referred after primary closure between 1990 and
      2015. Data were collected regarding patient gender, closure, osteotomy,
      immobilization, orthopedics and perioperative pain control. Univariate and
      multivariable analyses were performed to determine predictors of failure.
      RESULTS: A total of 156 patients met inclusion criteria. Overall failure rate was
      30% (13% from our institution and 87% from referrals). On multivariable analysis
      use of Buck traction (OR 0.11, 95% CI 0.02-0.60, p = 0.011) and immobilization
      time greater than 4 weeks (OR 0.19, 95% CI 0.04-0.86, p = 0.031) had
      significantly lower odds of failure. Osteotomy performed by general orthopedic
      surgeons had significantly higher odds of failure (OR 23.47, 95% CI 1.45-379.19,
      p = 0.027). Type of osteotomy and use of epidural anesthesia did not
      significantly impact failure rates. CONCLUSIONS: Proper immobilization with
      modified Buck traction and external fixation, immobilization time greater than 4
      weeks and undergoing osteotomy performed by a pediatric orthopedic surgeon are
      crucial factors for successful primary closure with osteotomy.

PMID- 27720783
TI  - Clinical Outcome of Patients with Fibrosis/Necrosis at Post-Chemotherapy
      Retroperitoneal Lymph Node Dissection for Advanced Germ Cell Tumors.
AB  - PURPOSE: Fibrosis accounts for approximately 50% of histological findings at post
      chemotherapy retroperitoneal lymph node dissection, and is associated with
      reported relapse rates of 10% to 15%. We characterized patients with fibrosis at
      post-chemotherapy retroperitoneal lymph node dissection and identified predictors
      of adverse outcomes in this group. MATERIALS AND METHODS: We reviewed the medical
      records of men who underwent post-chemotherapy retroperitoneal lymph node
      dissection between 1989 and 2013 with histological findings of necrosis/fibrosis.
      With few exceptions post-chemotherapy retroperitoneal lymph node dissection after
      1999 was performed with a bilateral template. Clinical, pathological and
      treatment related data were reported. Cox regression models were built to
      identify predictors of disease recurrence. RESULTS: The study cohort included 598
      men with a median age of 32 years (IQR 25-38). Most cases (397 of 547, 73%) were
      classified as IGCCCG good risk, with no significant differences in risk
      classification before and after 1999 (p=0.55). Median followup was 7.3 years (IQR
      3.2-12.3). The 5-year recurrence-free and overall survival rates were 94% and
      96%, respectively. Overall 36 patients had disease recurrence, most of which was
      distant or outside the retroperitoneal lymph node dissection template. Procedures
      performed after 1999 and the presence of embryonal cell carcinoma on primary
      histology were associated with improved recurrence-free survival on multivariate
      analysis (p <0.01). CONCLUSIONS: Disease recurrence in patients with fibrosis at
      post-chemotherapy retroperitoneal lymph node dissection is an uncommon yet
      significant event, which is less likely to occur in patients treated after 1999
      and in those with embryonal carcinoma on primary histology.

PMID- 27720782
TI  - Comparative Effectiveness of Cancer Control and Survival after Robot-Assisted
      versus Open Radical Prostatectomy.
AB  - PURPOSE: Robot-assisted surgery has been rapidly adopted in the U.S. for prostate
      cancer. Its adoption has been driven by market forces and patient preference, and
      debate continues regarding whether it offers improved outcomes to justify the
      higher cost relative to open surgery. We examined the comparative effectiveness
      of robot-assisted vs open radical prostatectomy in cancer control and survival in
      a nationally representative population. MATERIALS AND METHODS: This population
      based observational cohort study of patients with prostate cancer undergoing
      robot-assisted radical prostatectomy and open radical prostatectomy during 2003
      to 2012 used data captured in the SEER (Surveillance, Epidemiology, and End
      Results)-Medicare linked database. Propensity score matching and time to event
      analysis were used to compare all cause mortality, prostate cancer specific
      mortality and use of additional treatment after surgery. RESULTS: A total of
      6,430 robot-assisted radical prostatectomies and 9,161 open radical
      prostatectomies performed during 2003 to 2012 were identified. The use of robot
      assisted radical prostatectomy increased from 13.6% in 2003 to 2004 to 72.6% in
      2011 to 2012. After a median followup of 6.5 years (IQR 5.2-7.9) robot-assisted
      radical prostatectomy was associated with an equivalent risk of all cause
      mortality (HR 0.85, 0.72-1.01) and similar cancer specific mortality (HR 0.85,
      0.50-1.43) vs open radical prostatectomy. Robot-assisted radical prostatectomy
      was also associated with less use of additional treatment (HR 0.78, 0.70-0.86).
      CONCLUSIONS: Robot-assisted radical prostatectomy has comparable intermediate
      cancer control as evidenced by less use of additional postoperative cancer
      therapies and equivalent cancer specific and overall survival. Longer term
      followup is needed to assess for differences in prostate cancer specific
      survival, which was similar during intermediate followup. Our findings have
      significant quality and cost implications, and provide reassurance regarding the
      adoption of more expensive technology in the absence of randomized controlled
      trials.

PMID- 27720784
TI  - Resolving incongruence: Species of hybrid origin in Columnea (Gesneriaceae).
AB  - Speciation by hybridization has long been recognized among plants and includes
      both homoploid and allopolyploid speciation. The numbers of presumed hybrid
      species averages close to 11% and tends to be concentrated in a subset of
      angiosperm families. Recent advances in molecular methods have verified species
      of hybrid origin that had been presumed on the basis of morphology and have
      identified species that were not initially considered hybrids. Identifying
      species of hybrid origin is often a challenge and typically based on intermediate
      morphology, or discrepancies between molecular datasets. Discrepancies between
      data partitions may result from several factors including poor support,
      incomplete lineage sorting, or hybridization. A phylogenetic analysis of species
      in Columnea (Gesneriaceae) indicated significant incongruencies between the cpDNA
      and nrDNA datasets. Tests that examined whether one or both of the datasets had
      the phylogenetic signal to reject the topology of the alternate dataset
      (Shimodaira and Hasegawa [SH] and approximately unbiased [AU] tests) indicated
      significant differences between the topologies. Splitstree analyses also showed
      that there was support for the placement of the discrepant taxa in both datasets
      and that the combined data placed the putative hybrid species in an intermediate
      position between the two datasets. The genealogical sorting index (GSI) implied
      that coalescence in nrDNA had occurred in all species where more than a single
      individual had been sampled, but the GSI value was lower for the cpDNA of most of
      the putative hybrids, implying that these regions have not yet coalesced in these
      lineages despite being haploid. The JML test that evaluates simulated species
      pairwise distances against observed distances also implies that observed nrDNA
      data generate shorter distances than simulated data, implying hybridization. It
      is most likely that C. gigantifolia, C. rubriacuta, and C. sp. nov. represent a
      lineage from a hybrid ancestor, but C. moorei may be a more recent hybrid and may
      still be undergoing hybridization with sympatric species.

PMID- 27720785
TI  - Phylogenomics and species delimitation in the knob-scaled lizards of the genus
      Xenosaurus (Squamata: Xenosauridae) using ddRADseq data reveal a substantial
      underestimation of diversity.
AB  - Middle American knob-scaled lizards of the genus Xenosaurus are a unique
      radiation of viviparous species that are generally characterized by a flattened
      body shape and a crevice-dwelling ecology. Only eight species of Xenosaurus, one
      of them with five subspecies (X. grandis), have been formally described. However,
      species limits within Xenosaurus have never been examined using molecular data,
      and no complete phylogeny of the genus has been published. Here, we used ddRADseq
      data from all of the described and potentially undescribed taxa of Xenosaurus to
      investigate species limits, and to obtain a phylogenetic hypothesis for the
      genus. We analyzed the data using a variety of phylogenetic models, and were able
      to reconstruct a well-resolved and generally well-supported phylogeny for this
      group. We found Xenosaurus to be composed of four major, allopatric clades
      concordant with geography. The first and second clades that branch off the tree
      are distributed on the Atlantic slopes of the Sierra Madre Oriental and are
      composed of X. mendozai, X. platyceps, and X. newmanorum, and X.
      tzacualtipantecus and an undescribed species from Puebla, respectively. The third
      clade is distributed from the Atlantic slopes of the Mexican Transvolcanic Belt
      in west-central Veracruz south to the Pacific slopes of the Sierra Madre del Sur
      in Guerrero and Oaxaca, and is composed of X. g. grandis, X. rectocollaris, X.
      phalaroanthereon, X. g. agrenon, X. penai, and four undescribed species from
      Oaxaca. The last clade is composed of the four taxa that are geographically
      closest to the Isthmus of Tehuantepec (X. g. arboreus, X. g. rackhami, X. g.
      sanmartinensis, and an undescribed species from Oaxaca). We also utilized a
      variety of molecular species delimitation approaches, including analyses with
      GMYC, PTP, BPP, and BFD*, which suggested that species diversity in Xenosaurus is
      at least 30% higher than currently estimated.

PMID- 27720786
TI  - Impact of Radiation Therapy on Aggressive Care and Quality of Life Near Death.
AB  - CONTEXT: Radiation therapy (RT) is used with palliative intent in patients with
      advanced stage cancer. Prior studies, primarily in patients with poor performance
      status (PS), suggest that RT is associated with aggressive medical care, which
      may impact patients' quality of life near death (QoD) adversely. OBJECTIVE: This
      study examines associations between RT use and patients' receipt of aggressive
      care and QoD based on patients' PS. METHODS: This is a multi-institutional,
      prospective cohort study of patients with end-stage cancers (N = 312) who were
      identified as terminally ill at study enrollment. RT use (n = 24; 7.7%) and
      Eastern Cooperative Oncology Group (ECOG) PS were assessed at study entry (median
      = 3.8 months before death). Aggressive care near death was operationalized as use
      of mechanical ventilation and/or resuscitation in the last week of life. QoD was
      determined using validated caregiver ratings of patients' physical and mental
      distress in their final week. RESULTS: RT use was associated with higher QoD
      (8/8, 100.0%, vs. 58/114, 50.9%; P = 0.006) among patients with good PS (ECOG =
      1), more aggressive care near death (3/9, 33.3%, vs. 6/107, 5.6%; P = 0.020)
      among patients with moderate PS (ECOG = 2), and lower QoD (1/7, 14.3%, vs. 28/51,
      54.9%; P = 0.046) among patients with poor PS (ECOG = 3). CONCLUSIONS: Targeted
      use of RT in end-of-life cancer care may benefit patients with good PS, but its
      use may adversely affect patients with poorer PS. Decisions about RT use in this
      setting should consider likely end-of-life outcomes based on patients' current
      PS.

PMID- 27720788
TI  - Remaining Lifetime After Recognition of Terminal Illness Depends on Diagnosis: A
      Nationwide Population-Based Cohort Study.
AB  - CONTEXT: Timely recognition of the terminal phase of life will benefit patients
      and caregivers as it may facilitate advance care planning and support.
      OBJECTIVES: The objective of this study was to investigate the remaining lifetime
      of patients entering a physician-assessed terminal phase and to analyze variation
      in remaining lifetime according to diagnosis and sociodemographic factors.
      METHODS: Danish National Health Registers were used to establish a prospective
      cohort of adult patients formally registered with drug reimbursement due to
      terminal illness in 2012 and followed until June 2014. RESULTS: Of the 11,062
      included patients, the median remaining lifetime was 55 days and 37% of the
      patients died within the first month. The majority suffered from cancer (89%).
      Patients with a noncancer disease had the shortest remaining lifetime (17 days),
      considerably shorter than patients with cancer (59 days). Patients with prostate
      cancer had the longest remaining lifetime (76 days), whereas those with
      hematologic cancer had the shortest among cancer patients (41 days). Compared
      with lung cancer patients, the probability of death within 30 days were higher
      for patients with noncancer disease and lower for those with prostate or
      colorectal cancer. Male gender and high age were associated with higher risk of
      dying within 30 days. CONCLUSION: This study found a median remaining lifetime of
      55 days after recognition of terminal illness. Remaining lifetime differed
      between cancer and noncancer patients and according to age and gender. Increased
      attention should be directed toward timely recognition of the transition into the
      terminal phase, especially for patients with noncancer disease.

PMID- 27720787
TI  - Associations Between Neurotransmitter Genes and Fatigue and Energy Levels in
      Women After Breast Cancer Surgery.
AB  - CONTEXT: Fatigue is a common problem in oncology patients. Less is known about
      decrements in energy levels and the mechanisms that underlie both fatigue and
      energy. OBJECTIVES: In patients with breast cancer, variations in
      neurotransmitter genes between lower and higher fatigue latent classes and
      between the higher and lower energy latent classes were evaluated. METHODS:
      Patients completed assessments before and monthly for six months after surgery.
      Growth mixture modeling was used to identify distinct latent classes for fatigue
      severity and energy levels. Thirty candidate genes involved in various aspects of
      neurotransmission were evaluated. RESULTS: Eleven single-nucleotide polymorphisms
      or haplotypes (i.e., ADRB2 rs1042718, BDNF rs6265, COMT rs9332377, CYP3A4
      rs4646437, GALR1 rs949060, GCH1 rs3783642, NOS1 rs9658498, NOS1 rs2293052, NPY1R
      Haplotype A04, SLC6A2 rs17841327, and 5HTTLPR + rs25531 in SLC6A4) were
      associated with latent class membership for fatigue. Seven single-nucleotide
      polymorphisms or haplotypes (i.e., NOS1 rs471871, SLC6A1 rs2675163, SLC6A1
      Haplotype D01, SLC6A2 rs36027, SLC6A3 rs37022, SLC6A4 rs2020942, and TAC1
      rs2072100) were associated with latent class membership for energy. Three of 13
      genes (i.e., NOS1, SLC6A2, and SLC6A4) were associated with latent class
      membership for both fatigue and energy. CONCLUSIONS: Molecular findings support
      the hypothesis that fatigue and energy are distinct, yet related symptoms.
      Results suggest that a large number of neurotransmitters play a role in the
      development and maintenance of fatigue and energy levels in breast cancer
      patients.

PMID- 27720789
TI  - Assessment of Breathlessness in Lung Cancer: Psychometric Properties of the
      Dyspnea-12 Questionnaire.
AB  - CONTEXT: The Dyspnea-12 (D-12) Questionnaire is a well-validated instrument in
      respiratory illnesses for breathlessness assessment, but its psychometric
      properties have not been tested in lung cancer. OBJECTIVE: To demonstrate the
      psychometric properties of the D-12 in lung cancer patients. METHODS: Baseline
      data from a lung cancer feasibility trial were adopted for this analysis. D-12
      and a series of patient-reported tools, including five Numeric Rating Scales
      (NRS), the Hospital Anxiety and Depression Scale (HADS), and the Lung Cancer
      Symptom Scale (LCSS), were used for the psychometric assessment. Spearman's
      correlation coefficients (rs) were used to estimate the convergent validity of
      the D-12 with the NRS, HADS, and LCSS. Exploratory factor analysis was performed
      to examine construct validity. Reliability was tested by Cronbach's alpha and
      item-to-total correlations. D-12 score difference between patients with or
      without anxiety, depression, and chronic obstructive pulmonary disease (COPD) was
      explored to identify its discriminate performance. RESULTS: One hundred and one
      lung cancer patients were included. There were significantly positive
      correlations between the D-12 and the HADS, LCSS, and NRS measuring
      breathlessness severity and its associated affective distress. Factor analysis
      clearly identified two components (physical and emotional) of the D-12.
      Cronbach's alpha for D-12 total, physical, and emotional subscales was 0.95,
      0.92, and 0.94, respectively. Patients with anxiety or depression demonstrated
      significantly higher D-12 scores than those without it, and patients with COPD
      reported significantly more severe breathlessness than those without COPD.
      CONCLUSION: The D-12 is a valid and reliable self-reported questionnaire for use
      in breathlessness assessment in lung cancer patients.

PMID- 27720792
TI  - Capturing the Palliative Home Care Experience From Bereaved Caregivers Through
      Qualitative Survey Data: Toward Informing Quality Improvement.
AB  - CONTEXT: Measuring palliative care experience using patient-reported outcomes is
      becoming important for assessing and improving quality, although most validated
      outcome tools solely use scaled questions. OBJECTIVES: We analyzed open-text
      survey responses from bereaved caregivers to identify strengths and weaknesses in
      the quality of end-of-life care services and to assess the usefulness of
      qualitative survey data for quality improvement. METHODS: This was a
      retrospective observational study involving bereaved caregivers of decedents who
      had received palliative home care services in one of six health care regions in
      Ontario, Canada. Using the U.K.'s validated Views of Informal Carers-Evaluation
      of Services survey, respondents were asked what was good and what was bad about
      the services provided in the last three months of life as separate open-text
      questions. A qualitative constant comparison approach was used to derive themes
      from the responses. RESULTS: Among 330 caregivers who completed the survey, 271
      (82%) caregivers responded to the open-text questions: 93% of those commented on
      something that was good about care and 55% on something that was bad. The care
      experiences were generally positive, with the exception of specific individuals
      or settings that were perceived as adverse. The qualitative data were more
      informative about deficiencies in care compared with the quantitative data.
      CONCLUSION: The qualitative survey data in this study provided key
      recommendations toward making care more responsive to the needs of dying patients
      and their families. Capturing the narrative responses of bereaved caregivers is
      feasible and informative for palliative care program development.

PMID- 27720790
TI  - Validation of the Family Inpatient Communication Survey.
AB  - CONTEXT: Although many family members who make surrogate decisions report
      problems with communication, there is no validated instrument to accurately
      measure surrogate/clinician communication for older adults in the acute hospital
      setting. OBJECTIVES: The objective of this study was to validate a survey of
      surrogate-rated communication quality in the hospital that would be useful to
      clinicians, researchers, and health systems. METHODS: After expert review and
      cognitive interviewing (n = 10 surrogates), we enrolled 350 surrogates (250
      development sample and 100 validation sample) of hospitalized adults aged 65
      years and older from three hospitals in one metropolitan area. The communication
      survey and a measure of decision quality were administered within hospital days 3
      and 10. Mental health and satisfaction measures were administered six to eight
      weeks later. RESULTS: Factor analysis showed support for both one-factor (Total
      Communication) and two-factor models (Information and Emotional Support). Item
      reduction led to a final 30-item scale. For the validation sample, internal
      reliability (Cronbach's alpha) was 0.96 (total), 0.94 (Information), and 0.90
      (Emotional Support). Confirmatory factor analysis fit statistics were adequate
      (one-factor model, comparative fit index = 0.981, root mean square error of
      approximation = 0.62, weighted root mean square residual = 1.011; two-factor
      model comparative fit index = 0.984, root mean square error of approximation =
      0.055, weighted root mean square residual = 0.930). Total score and subscales
      showed significant associations with the Decision Conflict Scale (Pearson
      correlation -0.43, P < 0.001 for total score). Emotional Support was associated
      with improved mental health outcomes at six to eight weeks, such as anxiety (
      0.19 P < 0.001), and Information was associated with satisfaction with the
      hospital stay (0.49, P < 0.001). CONCLUSION: The survey shows high reliability
      and validity in measuring communication experiences for hospital surrogates. The
      scale has promise for measurement of communication quality and is predictive of
      important outcomes, such as surrogate satisfaction and well-being.

PMID- 27720791
TI  - Impact of Palliative Care Screening and Consultation in the ICU: A Multihospital
      Quality Improvement Project.
AB  - CONTEXT: There are few multicenter studies that examine the impact of systematic
      screening for palliative care and specialty consultation in the intensive care
      unit (ICU). OBJECTIVE: To determine the outcomes of receiving palliative care
      consultation (PCC) for patients who screened positive on palliative care referral
      criteria. METHODS: In a prospective quality assurance intervention with a
      retrospective analysis, the covariate balancing propensity score method was used
      to estimate the conditional probability of receiving a PCC and to balance
      important covariates. For patients with and without PCCs, outcomes studied were
      as follows: 1) change to "do not resuscitate" (DNR), 2) discharge to hospice, 3)
      30-day readmission, 4) hospital length of stay (LOS), 5) total direct hospital
      costs. RESULTS: In 405 patients with positive screens, 161 (40%) who received a
      PCC were compared to 244 who did not. Patients receiving PCCs had higher rates of
      DNR-adjusted odds ratio (AOR) = 7.5; 95% CI 5.6-9.9) and hospice referrals-(AOR =
      7.6; 95% CI 5.0-11.7). They had slightly lower 30-day readmissions-(AOR = 0.7;
      95% CI 0.5-1.0); no overall difference in direct costs or LOS was found between
      the two groups. When patients receiving PCCs were stratified by time to PCC
      initiation, early consultation-by Day 4 of admission-was associated with
      reductions in LOS (1.7 days [95% CI -3.1, -1.2]) and average direct variable
      costs (-$1815 [95% CI -$3322, -$803]) compared to those who received no PCC.
      CONCLUSION: Receiving a PCC in the ICUs was significantly associated with more
      frequent DNR code status and hospice referrals, but not 30-day readmissions or
      hospital utilization. Early PCC was associated with significant LOS and direct
      cost reductions. Providing PCC early in the ICU should be considered.

PMID- 27720793
TI  - Timing of Advance Directive Completion and Relationship to Care Preferences.
AB  - CONTEXT: Given recent Medicare rules reimbursing clinicians for engaging in
      advance care planning, there is heightened need to understand factors associated
      with the timing of advance directive (AD) completion before death and how the
      timing impacts care decisions. OBJECTIVE: The purpose of this study was to
      investigate patterns in timing of AD completion and the relationship between
      timing and documented care preferences. We hypothesize that ADs completed late in
      the course of illness or very early in the disease trajectory will reflect higher
      preferences for aggressive care. METHODS: We conducted a retrospective study
      using logistic regressions to analyze data from the Health and Retirement Study,
      a nationally representative longitudinal survey of older adults. RESULTS: The
      analytic sample included exit interviews conducted from 2000 to 2012 among 2904
      proxy reporters of deceased participants who had an AD. Nearly three-quarters
      (71%) of ADs were completed a year or more before death. Being younger or a
      racial/ethnic minority, and having lower education, a diagnosis of cancer or lung
      disease, and an expected death were associated with completing an AD within the
      three months before death, while having the lowest quartile of assets and memory
      problems were inversely associated with AD completion. Minorities, those with
      lower education, expected death, and timing of AD completion were associated with
      electing aggressive care. CONCLUSION: Early documentation of care wishes may not
      be associated with an increased likelihood of electing aggressive care; however,
      ADs completed in the last months of life have higher rates of election of
      aggressive care.

PMID- 27720794
TI  - Mindfulness-Based Stress Reduction in Post-treatment Breast Cancer Patients:
      Immediate and Sustained Effects Across Multiple Symptom Clusters.
AB  - CONTEXT: Breast cancer survivors (BCS) face adverse physical and psychological
      symptoms, often co-occurring. Biologic and psychological factors may link
      symptoms within clusters, distinguishable by prevalence and/or severity. Few
      studies have examined the effects of behavioral interventions or treatment of
      symptom clusters. OBJECTIVES: The aim of this study was to identify symptom
      clusters among post-treatment BCS and determine symptom cluster improvement
      following the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR(BC))
      program. METHODS: Three hundred twenty-two Stage 0-III post-treatment BCS were
      randomly assigned to either a six-week MBSR(BC) program or usual care.
      Psychological (depression, anxiety, stress, and fear of recurrence), physical
      (fatigue, pain, sleep, and drowsiness), and cognitive symptoms and quality of
      life were assessed at baseline, six, and 12 weeks, along with demographic and
      clinical history data at baseline. A three-step analytic process included the
      error-accounting models of factor analysis and structural equation modeling.
      RESULTS: Four symptom clusters emerged at baseline: pain, psychological, fatigue,
      and cognitive. From baseline to six weeks, the model demonstrated evidence of
      MBSR(BC) effectiveness in both the psychological (anxiety, depression, perceived
      stress and QOL, emotional well-being) (P = 0.007) and fatigue (fatigue, sleep,
      and drowsiness) (P < 0.001) clusters. Results between six and 12 weeks showed
      sustained effects, but further improvement was not observed. CONCLUSION: Our
      results provide clinical effectiveness evidence that MBSR(BC) works to improve
      symptom clusters, particularly for psychological and fatigue symptom clusters,
      with the greatest improvement occurring during the six-week program with
      sustained effects for several weeks after MBSR(BC) training. TRIAL REGISTRATION:
      Name and URL of Registry: ClinicalTrials.gov. Registration number: NCT01177124.

PMID- 27720795
TI  - Chronic 14-day exposure to insecticides or methylmercury modulates neuronal
      activity in primary rat cortical cultures.
AB  - There is an increasing demand for in vitro test systems to detect neurotoxicity
      for use in chemical risk assessment. In this study, we evaluated the
      applicability of rat primary cortical cultures grown on multi-well micro
      electrode arrays (mwMEAs) to detect effects of chronic 14-day exposure to
      structurally different insecticides or methylmercury on neuronal activity (mean
      spike rate; MSR). Effects of chronic exposure to alpha-cypermethrin, endosulfan,
      carbaryl, chlorpyrifos(-oxon), methylmercury or solvent control [14days exposure,
      initiated after baseline recording at day in vitro (DIV)7] were studied in five
      successive recordings between DIV10 and DIV21. The results were compared to
      effects of acute exposure to these same compounds (activity recorded immediately
      after the start of exposure after baseline recording at DIV10-11). Chronic 14-day
      exposure to methylmercury, chlorpyrifos and alpha-cypermethrin inhibited MSR, all
      with a lowest-observed effect concentration (LOEC) of 0.1MUM, while exposure to
      endosulfan increased MSR [LOEC: 1MUM]. No significant effects were observed for
      chlorpyrifos-oxon and carbaryl. Similar to the observations in the chronic 14-day
      exposure studies, MSR was inhibited by acute 30-min exposure to methylmercury,
      chlorpyrifos, and alpha-cypermethrin [LOECs: 1MUM, 10MUM, and 1MUM,
      respectively], whereas endosulfan increased MSR [LOEC: 0.3MUM]. While not
      observed in the chronic 14-day exposure study, acute exposure to chlorpyrifos
      oxon and carbaryl resulted in inhibition of MSR [LOECs: 10MUM, and100 MUM,
      respectively]. Effects on median interspike intervals (mISI; a measure for
      neuronal firing pattern) were not detected following chronic 14-day or acute 30
      min exposure, except for increased mISI at acute chlorpyrifos and alpha
      cypermethrin exposures at concentrations that also inhibited MSR. These data
      indicate that the effects of chronic 14-day exposures to methylmercury and
      insecticides at low concentrations on spontaneous neuronal activity in vitro can
      be predicted in rapid acute screening studies using mwMEAs.

PMID- 27720796
TI  - Modeling U-shaped dose-response curves for manganese using categorical
      regression.
AB  - INTRODUCTION: Manganese is an essential nutrient which can cause adverse effects
      if ingested to excess or in insufficient amounts, leading to a U-shaped exposure
      response relationship. Methods have recently been developed to describe such
      relationships by simultaneously modeling the exposure-response curves for excess
      and deficiency. These methods incorporate information from studies with diverse
      adverse health outcomes within the same analysis by assigning severity scores to
      achieve a common response metric for exposure-response modeling. OBJECTIVE: We
      aimed to provide an estimate of the optimal dietary intake of manganese to
      balance adverse effects from deficient or excess intake. METHODS: We undertook a
      systematic review of the literature from 1930 to 2013 and extracted information
      on adverse effects from manganese deficiency and excess to create a database on
      manganese toxicity following oral exposure. Although data were available for
      seven different species, only the data from rats was sufficiently comprehensive
      to support analytical modelling. The toxicological outcomes were standardized on
      an 18-point severity scale, allowing for a common analysis of all available
      toxicological data. Logistic regression modelling was used to simultaneously
      estimate the exposure-response profile for dietary deficiency and excess for
      manganese and generate a U-shaped exposure-response curve for all outcomes.
      RESULTS: Data were available on the adverse effects of 6113 rats. The nadir of
      the U-shaped joint response curve occurred at a manganese intake of
      2.70mg/kgbw/day with a 95% confidence interval of 2.51-3.02. The extremes of both
      deficient and excess intake were associated with a 90% probability of some
      measurable adverse event. CONCLUSION: The manganese database supports estimation
      of optimal intake based on combining information on adverse effects from
      systematic review of published experiments. There is a need for more studies on
      humans. Translation of our results from rats to humans will require adjustment
      for interspecies differences in sensitivity to manganese.

PMID- 27720797
TI  - Neuronal prolyl-4-hydroxylase 2 deficiency improves cognitive abilities in a
      murine model of cerebral hypoperfusion.
AB  - Episodes of cerebral hypoxia/ischemia increase the risk of dementia, which is
      associated with impaired learning and memory. Previous studies in rodent models
      of dementia indicated a favorable effect of the hypoxia-inducible factor (HIF)
      targets VEGF (vascular endothelial growth factor) and erythropoietin (Epo). In
      the present study we thus investigated whether activation of the entire adaptive
      HIF pathway in neurons by cell-specific deletion of the HIF suppressor prolyl-4
      hydroxylase 2 (PHD2) improves cognitive abilities in young (3months) and old (18
      28months) mice suffering from chronic brain hypoperfusion. Mice underwent
      permanent occlusion of the left common carotid artery, and cognitive function was
      assessed using the Morris water navigation task. Under conditions of both normal
      and decreased brain perfusion, neuronal PHD2 deficiency resulted in improved and
      faster spatial learning in young mice, which was preserved to some extent also in
      old animals. The loss of PHD2 in neurons resulted in enhanced hippocampal mRNA
      and protein levels of Epo and VEGF, but did not alter local microvascular
      density, dendritic spine morphology, or expression of synaptic plasticity-related
      genes in the hippocampus. Instead, better cognitive function in PHD2 deficient
      animals was accompanied by an increased number of neuronal precursor cells along
      the subgranular zone of the dentate gyrus. Overall, our current pre-clinical
      findings indicate an important role for the endogenous oxygen sensing machinery,
      encompassing PHDs, HIFs and HIF target genes, for proper cognitive function.
      Thus, pharmacological compounds affecting the PHD-HIF axis might well be suited
      to treat cognitive dysfunction and neurodegenerative processes.

PMID- 27720799
TI  - Deletion of exons 3 and 4 in the mouse Nr1d1 gene worsens high-fat diet-induced
      hepatic steatosis.
AB  - AIMS: To elucidate the role of nuclear receptor subfamily 1, group D, member 1
      (Nr1d1) in hepatic lipid metabolism and pathogenesis of nonalcoholic fatty liver
      diseases, Nr1d1 gene mutant mice, in which the DNA-binding domain (exons 3 and 4)
      was deleted (Nr1d1 Deltaex3/4), were challenged with a high-fat diet (HFD), and
      the gene expression patterns that responded to this alteration were profiled.
      MAIN METHODS: The Nr1d1 Deltaex3/4 mice were fed an HFD for 12weeks. Liver
      tissues were examined by histology, and lipid droplets were detected by Oil-Red O
      staining. Serum biochemical analyses were performed to assess markers of liver
      injury. Microarray analysis was used to profile hepatic gene expression patterns.
      Functional annotation, upstream prediction, and gene coexpression prediction
      analyses were performed. KEY FINDINGS: The Nr1d1 Deltaex3/4 mice showed enhanced
      hepatic steatosis after being challenged with an HFD, but not with a low-fat
      diet, indicating an interaction between diet and genotype for this phenotypic
      change. Gene expression profiling revealed that this interaction might involve
      neutrophil recruitment and the cyclic adenosine monophosphate metabolic pathway.
      A study of transcription factor binding site enrichment suggested that
      CCAAT/enhancer-binding protein alpha and hepatocyte nuclear factor 4 alpha were
      associated with this phenotypic change. SIGNIFICANCE: Loss of DNA binding of
      Nr1d1 was associated with a deterioration in hepatic steatosis. The interaction
      between the Nr1d1 Deltaex3/4 genotype with an HFD might mediate these phenotypic
      changes, probably through a nonclassical transcriptional function of Nr1d1.

PMID- 27720798
TI  - Blast waves from detonated military explosive reduce GluR1 and synaptophysin
      levels in hippocampal slice cultures.
AB  - Explosives create shockwaves that cause blast-induced neurotrauma, one of the
      most common types of traumatic brain injury (TBI) linked to military service.
      Blast-induced TBIs are often associated with reduced cognitive and behavioral
      functions due to a variety of factors. To study the direct effects of military
      explosive blasts on brain tissue, we removed systemic factors by utilizing rat
      hippocampal slice cultures. The long-term slice cultures were briefly sealed air
      tight in serum-free medium, lowered into a 37 degrees C water-filled tank, and
      small 1.7-gram assemblies of cyclotrimethylene trinitramine (RDX) were detonated
      15cm outside the tank, creating a distinct shockwave recorded at the culture
      plate position. Compared to control mock-treated groups of slices that received
      equal submerge time, 1-3 blast impacts caused a dose-dependent reduction in the
      AMPA receptor subunit GluR1. While only a small reduction was found in
      hippocampal slices exposed to a single RDX blast and harvested 1-2days later,
      slices that received two consecutive RDX blasts 4min apart exhibited a 26-40%
      reduction in GluR1, and the receptor subunit was further reduced by 64-72% after
      three consecutive blasts. Such loss correlated with increased levels of HDAC2, a
      histone deacetylase implicated in stress-induced reduction of glutamatergic
      transmission. No evidence of synaptic marker recovery was found at 72h post
      blast. The presynaptic marker synaptophysin was found to have similar
      susceptibility as GluR1 to the multiple explosive detonations. In contrast to the
      synaptic protein reductions, actin levels were unchanged, spectrin breakdown was
      not detected, and Fluoro-Jade B staining found no indication of degenerating
      neurons in slices exposed to three RDX blasts, suggesting that small, sub-lethal
      explosives are capable of producing selective alterations to synaptic integrity.
      Together, these results indicate that blast waves from military explosive cause
      signs of synaptic compromise without producing severe neurodegeneration, perhaps
      explaining the cognitive and behavioral changes in those blast-induced TBI
      sufferers that have no detectable neuropathology.

PMID- 27720800
TI  - Redox signaling in rheumatoid arthritis and the preventive role of polyphenols.
AB  - Rheumatoid arthritis (RA) is an autoimmune, inflammatory joint disease whose
      exact cause is still not completely known. Reactive oxygen species (ROS) are
      believed to be involved in the pathogenesis of RA. ROS are produced mostly by the
      phagocytic cells during oxidative burst and oxidative phosphorylation. Lipids,
      proteins and nucleic acids get damaged by the overproduction of ROS. Damaging
      effects of ROS are taken care by the enzymatic and non-enzymatic defence system
      of the body. Overproduction or inadequate elimination of reactive species leading
      to oxidative stress has been positively correlated with the disease severity in
      RA patients. ROS activates signal transduction pathways involved in the
      inflammatory response in RA. Understanding the complex interplay between
      signaling pathways might be useful for the development of new and effective
      therapeutics for RA. In this review we discuss the involvement of reactive
      species in the pathogenesis of RA and their elimination by antioxidant defence
      system. Role of various antioxidants/polyphenols which looks quite promising in
      the treatment of RA have also been discussed.

PMID- 27720801
TI  - Acute bouts of wheel running decrease cocaine self-administration: Influence of
      exercise output.
AB  - Exercise is associated with lower rates of drug use in human populations and
      decreases drug self-administration in laboratory animals. Most of the existing
      literature examining the link between exercise and drug use has focused on
      chronic, long-term exercise, and very few studies have examined the link between
      exercise output (i.e., amount of exercise) and drug self-administration. The
      purpose of this study was to examine the effects of acute bouts of exercise on
      cocaine self-administration, and to determine whether these effects were
      dependent on exercise output and the time interval between exercise and drug self
      administration. Female rats were trained to run in automated running wheels,
      implanted with intravenous catheters, and allowed to self-administer cocaine on a
      fixed ratio (FR1) schedule of reinforcement. Immediately prior to each test
      session, subjects engaged in acute bouts of exercise in which they ran for 0, 30,
      or 60min at 12m/min. Acute bouts of exercise before test sessions decreased
      cocaine self-administration in an output-dependent manner, with the greatest
      reduction in cocaine intake observed in the 60-min exercise condition. Exercise
      did not reduce cocaine self-administration when wheel running and test sessions
      were separated by 12h, and exercise did not reduce responding maintained by food
      or responding during a saline substitution test. These data indicate that acute
      bouts of exercise decrease cocaine self-administration in a time- and output
      dependent manner. These results also add to a growing body of literature
      suggesting that physical activity may be an effective component of drug abuse
      treatment programs.

PMID- 27720802
TI  - In silico metabolic engineering of Clostridium ljungdahlii for synthesis gas
      fermentation.
AB  - Synthesis gas fermentation is one of the most promising routes to convert
      synthesis gas (syngas; mainly comprised of H2 and CO) to renewable liquid fuels
      and chemicals by specialized bacteria. The most commonly studied syngas
      fermenting bacterium is Clostridium ljungdahlii, which produces acetate and
      ethanol as its primary metabolic byproducts. Engineering of C. ljungdahlii
      metabolism to overproduce ethanol, enhance the synthesize of the native
      byproducts lactate and 2,3-butanediol, and introduce the synthesis of non-native
      products such as butanol and butyrate has substantial commercial value. We
      performed in silico metabolic engineering studies using a genome-scale
      reconstruction of C. ljungdahlii metabolism and the OptKnock computational
      framework to identify gene knockouts that were predicted to enhance the synthesis
      of these native products and non-native products, introduced through insertion of
      the necessary heterologous pathways. The OptKnock derived strategies were often
      difficult to assess because increase product synthesis was invariably accompanied
      by decreased growth. Therefore, the OptKnock strategies were further evaluated
      using a spatiotemporal metabolic model of a syngas bubble column reactor, a
      popular technology for large-scale gas fermentation. Unlike flux balance
      analysis, the bubble column model accounted for the complex tradeoffs between
      increased product synthesis and reduced growth rates of engineered mutants within
      the spatially varying column environment. The two-stage methodology for deriving
      and evaluating metabolic engineering strategies was shown to yield new C.
      ljungdahlii gene targets that offer the potential for increased product synthesis
      under realistic syngas fermentation conditions.

PMID- 27720804
TI  - Hepatitis C testing in U.S. veterans born 1945-1965: An update.

PMID- 27720803
TI  - The gut microbiota contributes to a mouse model of spontaneous bile duct
      inflammation.
AB  - BACKGROUND & AIMS: A strong association between human inflammatory biliary
      diseases and gut inflammation has led to the hypothesis that gut microbes and
      lymphocytes activated in the intestine play a role in biliary inflammation. The
      NOD.c3c4 mouse model develops spontaneous biliary inflammation in extra- and
      intrahepatic bile ducts. We aimed to clarify the role of the gut microbiota in
      the biliary disease of NOD.c3c4 mice. METHODS: We sampled cecal content and
      mucosa from conventionally raised (CONV-R) NOD.c3c4 and NOD control mice,
      extracted DNA and performed 16S rRNA sequencing. NOD.c3c4 mice were rederived
      into a germ free (GF) facility and compared with CONV-R NOD.c3c4 mice. NOD.c3c4
      mice were also co-housed with NOD mice and received antibiotics from weaning.
      RESULTS: The gut microbial profiles of mice with and without biliary disease were
      different both before and after rederivation (unweighted UniFrac-distance). GF
      NOD.c3c4 mice had less distended extra-hepatic bile ducts than CONV-R NOD.c3c4
      mice, while antibiotic treated mice showed reduction of biliary infarcts. GF
      animals also showed a reduction in liver weight compared with CONV-R NOD.c3c4
      mice, and this was also observed in antibiotic treated NOD.c3c4 mice. Co-housing
      of NOD and NOD.c3c4 mice indicated that the biliary phenotype was neither
      transmissible nor treatable by co-housing with healthy mice. CONCLUSIONS:
      NOD.c3c4 and NOD control mice show marked differences in the gut microbiota. GF
      NOD.c3c4 mice develop a milder biliary affection compared with conventionally
      raised NOD.c3c4 mice. Our findings suggest that the intestinal microbiota
      contributes to disease in this murine model of biliary inflammation. LAY SUMMARY:
      Mice with liver disease have a gut microflora (microbiota) that differs
      substantially from normal mice. In a normal environment, these mice spontaneously
      develop disease in their bile ducts. However, when these mice, are raised in an
      environment devoid of bacteria, the disease in the bile ducts diminishes. Overall
      this clearly indicates that the bacteria in the gut (the gut microbiota)
      influences the liver disease in these mice.

PMID- 27720805
TI  - Gadolinium tissue deposition in brain and bone.
AB  - Until recognition of the association of nephrogenic systemic fibrosis (NSF) and
      gadolinium based contrast agents (GBCA) in 2006, these agents were considered
      extremely safe and without major adverse effects. Even after the recognition of
      NSF, most physicians considered all GBCAs to be safe when used in patients with
      normal renal function. This belief has been called into question with the
      discovery by Kanda in 2014 that gadolinium (Gd) is deposited in brain tissue in
      patients with normal kidney function. Since that initial report, there have been
      a number of important studies analyzing the effects of various GBCAs in brain
      using MR T1 signal intensity measurements and postmortem tissue analyses with
      inductively coupled plasma mass spectrometry. From these our knowledge and
      understanding of some key issues surrounding these observations has rapidly
      evolved. This report reviews and summarizes many recent human and animal studies
      in combination with past studies to better understand Gd tissue deposition not
      only in brain but also in bone and skin. Brain tissue deposition was initially
      demonstrated to occur with less stable group 1 linear agents but recent
      postmortem studies now confirm that Gd deposition also occurs with more stable
      linear agents as well as with macrocyclic agents although at much lower levels.
      Although no adverse health effects have been documented to date, even for the
      group 1 agents that deposit Gd in higher amounts, the implications for possible
      unrecognized toxicity is discussed. Future studies are being pursued that may
      provide better understanding of the various chemical forms of Gd that are
      deposited in tissues. This may help elucidate relative risks of different types
      of agents, mechanisms involved and even recognition of potential downstream toxic
      effects.

PMID- 27720806
TI  - Cluster analysis of quantitative MRI T2 and T1rho relaxation times of cartilage
      identifies differences between healthy and ACL-injured individuals at 3T.
AB  - PURPOSE: To identify focal lesions of elevated MRI T2 and T1rho relaxation times
      in articular cartilage of an ACL-injured group using a novel cluster analysis
      technique. MATERIALS AND METHODS: Eighteen ACL-injured patients underwent 3T MRI
      T2 and T1rho relaxometry at baseline, 6 months and 1 year and six healthy
      volunteers at baseline, 1 day and 1 year. Clusters of contiguous pixels above or
      below T2 and T1rho intensity and area thresholds were identified on a projection
      map of the 3D femoral cartilage surface. The total area of femoral cartilage
      plate covered by clusters (%CA) was split into areas above (%CA+) and below (%CA
      ) the thresholds and the differences in %CA(+ or -) over time in the ACL-injured
      group were determined using the Wilcoxon signed rank test. RESULTS: %CA+ was
      greater in the ACL-injured patients than the healthy volunteers at 6 months and 1
      year with average %CA+ of 5.2 +/- 4.0% (p = 0.0054) and 6.6 +/- 3.7% (p = 0.0041)
      for T2 and 6.2 +/- 7.1% (p = 0.063) and 8.2 +/- 6.9% (p = 0.042) for T1rho,
      respectively. %CA- at 6 months and 1 year was 3.0 +/- 1.8% (p > 0.1) and 5.9 +/-
      5.0% (p > 0.1) for T2 and 4.4 +/- 4.9% (p > 0.1) and 4.5 +/- 4.6% (p > 0.1) for
      T1rho, respectively. CONCLUSION: With the proposed cluster analysis technique, we
      have quantified cartilage lesion coverage and demonstrated that the ACL-injured
      group had greater areas of elevated T2 and T1rho relaxation times as compared to
      healthy volunteers.

PMID- 27720808
TI  - Immune and inflammatory responses to DNA damage in cancer and aging.
AB  - Genome instability is a hallmark of both cancer and aging processes. Beyond cell
      autonomous responses, it is known that DNA damage also elicits systemic
      mechanisms aimed at favoring survival and damaged cells clearance. Among these
      mechanisms, immune activation and NF-kappaB-mediated inflammation play central
      roles in organismal control of DNA damage. We focus herein on the different
      experimental evidences that have allowed gaining mechanistic insight about this
      relationship. We also describe the functional consequences of defective immune
      function in cancer development and age-related alterations. Finally, we discuss
      different intervention strategies based on enhancing immunity or on the
      modulation of the inflammatory response to improve organism homeostasis in cancer
      and aging.

PMID- 27720807
TI  - Mechanical sensitivity and electrophysiological properties of acutely dissociated
      dorsal root ganglion neurons of rats.
AB  - Primary afferent fibers use mechanically activated (MA) currents to transduce
      innocuous and noxious mechanical stimuli. However, it is largely unknown about
      the differences in MA currents between the afferents for sensing innocuous and
      noxious stimuli. In the present study, we used dorsal root ganglion (DRG) neurons
      acutely dissociated from rats and studied their MA currents and also their
      intrinsic membrane properties. Recorded from small-sized DRG neurons, we found
      that most of these neurons were mechanically sensitive (MS) showing MA currents.
      The MS neurons could be classified into nociceptive-like mechanically sensitive
      (Noci-MS) and non-nociceptive-like mechanically sensitive (nonNoci-MS) neurons
      based on their action potential shapes. Noci-MS neurons responded to mechanical
      stimulation with three types of MA currents, rapidly adapting (RA),
      intermediately adapting (IA), and slowly adapting (SA) currents. In contrast,
      almost all nonNoci-MS neurons showed RA current type in response to mechanical
      stimulation. Mechanical thresholds had a broad range for both nonNoci-MS and Noci
      MS neurons, and the thresholds were not significantly different between them.
      However, MA current densities were significantly smaller in Noci-MS than in
      nonNoci-MS neurons. Noci-MS and nonNoci-MS neurons also showed significant
      differences in their electrophysiological properties including action potential
      (AP) thresholds and AP firing patterns. These differences may contribute to the
      differential sensory encoding for innocuous and noxious mechanical stimuli.

PMID- 27720809
TI  - Persistent strengthening of the prefrontal cortex - nucleus accumbens pathway
      during incubation of cocaine-seeking behavior.
AB  - High rates of relapse after prolonged abstinence are often triggered by exposure
      to drug-associated cues that induce drug craving. Incubation of drug craving is a
      phenomenon that consists of time-dependent increases in cue-induced drug craving
      during withdrawal. Plasticity mechanisms in the nucleus accumbens (NAc) underlie
      drug-seeking responses and involve changes in excitatory synaptic transmission's
      efficacy. In particular, the prefrontal cortex (PFC) glutamatergic input to the
      NAc core has been well characterized regarding cocaine-evoked plasticity
      following non-contingent versus contingent exposure to cocaine or alternatively
      after protracted abstinence. Still, the synaptic strength during the course of
      withdrawal compared to drug-naive condition is unknown, since
      electrophysiological characterizations are mainly performed in brain slices or
      focus on distinct time points during cocaine-evoked plasticity in vivo. Here we
      used an incubation paradigm, in which rats had extended accessed to cocaine self
      administration, and underwent cue-induced reinstatement at withdrawal day 1 and
      30. Longitudinal in vivo field potential recordings in awake rats showed that
      chronic contingent exposure to cocaine strengthened the prelimbic PFC to NAc core
      pathway when compared to pre-cocaine condition. This strengthening was associated
      with decreased paired-pulse ratios (PPR), indicative of presynaptic enhancement
      of glutamate release, which persisted throughout withdrawal. Moreover, both field
      potential increase and PPR reduction after chronic cocaine exposure correlated
      with the number of cocaine infusions received during training. The present
      results together with previous findings of withdrawal-dependent postsynaptic
      enhancement of the PFC-NAc core pathway, suggest an additional presynaptic
      strengthening that is initiated during self-administration and maintained
      throughout abstinence in drug-seeking rats. These cocaine-driven neuroadaptations
      may provide a neural substrate for maladaptive processing of cues that can
      ultimately trigger craving and relapse.

PMID- 27720810
TI  - Impaired fear extinction retention and increased anxiety-like behaviours induced
      by limited daily access to a high-fat/high-sugar diet in male rats: Implications
      for diet-induced prefrontal cortex dysregulation.
AB  - Anxiety disorders and obesity are both common in youth and young adults. Despite
      increasing evidence that over-consumption of palatable high-fat/high-sugar "junk"
      foods leads to adverse neurocognitive outcomes, little is known about the effects
      of palatable diets on emotional memories and fear regulation. In the present
      experiments we examined the effects of daily 2h consumption of a high-fat/high
      sugar (HFHS) food across adolescence on fear inhibition and anxiety-like
      behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired
      retention of fear extinction and increased anxiety-like behaviour in an emergence
      test compared to rats fed a standard diet. The HFHS-fed rats displayed diet
      induced changes in prefrontal cortex (PFC) function which were detected by
      altered expression of GABAergic parvalbumin-expressing inhibitory interneurons
      and the stable transcription factor DeltaFosB which accumulates in the PFC in
      response to chronic stimuli. Immunohistochemical analyses of the medial PFC
      revealed that animals fed the HFHS diet had fewer parvalbumin-expressing cells
      and increased levels of FosB/DeltaFosB expression in the infralimbic cortex, a
      region implicated in the consolidation of fear extinction. There was a trend
      towards increased IBA-1 immunoreactivity, a marker of microglial activation, in
      the infralimbic cortex after HFHS diet exposure but expression of the
      extracellular glycoprotein reelin was unaffected. These findings demonstrate that
      a HFHS diet during adolescence is associated with reductions of prefrontal
      parvalbumin neurons and impaired fear inhibition in adulthood. Adverse effects of
      HFHS diets on the mechanisms of fear regulation may precipitate a vulnerability
      in obese individuals to the development of anxiety disorders.

PMID- 27720811
TI  - Differential gene expression underlying ovarian phenotype determination in honey
      bee, Apis mellifera L., caste development.
AB  - Adult honey bee queens and workers drastically differ in ovary size. This adult
      ovary phenotype difference becomes established during the final larval instar,
      when massive programmed cell death leads to the degeneration of 95-99% of the
      ovariole anlagen in workers. The higher juvenile hormone (JH) levels in queen
      larvae protect the ovaries against such degeneration. To gain insights into the
      molecular architecture underlying this divergence critical for adult caste fate
      and worker sterility, we performed a microarray analysis on fourth and early
      fifth instar queen and worker ovaries. For the fourth instar we found nine
      differentially expressed genes (DEGs) with log2FC > 1.0, but this number
      increased to 56 in early fifth-instar ovaries. We selected 15 DEGs for
      quantitative PCR (RT-qPCR) analysis. Nine differed significantly by the variables
      caste and/or development. Interestingly, genes with enzyme functions were higher
      expressed in workers, while those related to transcription and signaling had
      higher transcript levels in queens. For the RT-qPCR confirmed genes we analyzed
      their response to JH. This revealed a significant up-regulation for two genes, a
      short chain dehydrogenase reductase (sdr) and a heat shock protein 90 (hsp90).
      Five other genes, including hsp60 and hexamerin 70b (hex70b), were significantly
      down-regulated by JH. The sdr gene had previously come up as differentially
      expressed in other transcriptome analyses on honey bee larvae and heat shock
      proteins are frequently involved in insect hormone responses, this making them
      interesting candidates for further functional assays.

PMID- 27720812
TI  - Exercises and Dry Needling for Subacromial Pain Syndrome: A Randomized Parallel
      Group Trial.
AB  - : This randomized clinical trial investigated the effectiveness of exercise
      versus exercise plus trigger point (TrP) dry needling (TrP-DN) in subacromial
      pain syndrome. A randomized parallel-group trial, with 1-year follow-up was
      conducted. Fifty subjects with subacromial pain syndrome were randomly allocated
      to receive exercise alone or exercise plus TrP-DN. Participants in both groups
      were asked to perform an exercise program of the rotator cuff muscles twice daily
      for 5 weeks. Further, patients allocated to the exercise plus TrP-DN group also
      received dry needling to active TrPs in the muscles reproducing shoulder symptoms
      during the second and fourth sessions. The primary outcome was pain-related
      disability assessed using the Disabilities of the Arm, Shoulder, and Hand
      questionnaire. Secondary outcomes included mean current pain and the worst pain
      experienced in the shoulder during the previous week. They were assessed at
      baseline, 1 week, and 3, 6, and 12 months after the end of treatment. Analysis
      was according to intention to treat with mixed analysis of covariance adjusted
      for baseline outcomes. At 12 months, 47 patients (94%) completed follow-up.
      Statistically larger improvements (all, P < .01) in shoulder disability was found
      for the exercise plus TrP-DN group at all follow-up periods (post: Delta -20.6
      [95% confidence interval (CI) -23.8 to -17.4]; 3 months: Delta -23.2 [95% CI 
      28.3 to -18.1)]; 6 months: Delta -23.6 [95% CI -28.9 to -18.3]; 12 months: Delta 
      13.9 [95% CI -17.5 to -10.3]). Both groups exhibited similar improvements in
      shoulder pain outcomes at all follow-up periods. The inclusion of TrP-DN with an
      exercise program was effective for improving disability in subacromial pain
      syndrome. No greater improvements in shoulder pain were observed. PERSPECTIVE:
      This study found that the inclusion of 2 sessions of TrP-DN into an exercise
      program was effective for improving shoulder pain-related disability at short-,
      medium-, and long-term; however, no greater improvement in shoulder pain was
      observed.

PMID- 27720813
TI  - Contribution of amygdala to the pressor response elicited by microinjection of
      angiotensin II into the bed nucleus of the stria terminalis.
AB  - The bed nucleus of the stria terminalis (BST) is part of the limbic system
      located in the rostral forebrain. BST is involved in behavioral, neuroendocrine
      and autonomic functions, including cardiovascular regulation. The amygdala, plays
      an important role in mediating the behavioral and physiological responses
      associated with fear and anxiety, including cardiovascular responses. In a
      previous study, we showed that microinjection of AngII into the BST produced a
      pressor and two types of single-unit responses in the BST, short excitatory and
      long inhibitory. This study was performed to find possible involvement of
      amygdala in cardiovascular responses elicited by microinjection of AngII into the
      BST, using blockade of the central nucleus of amygdala (CeA) and single unit
      recording from the CeA, while injecting AngII into the BST in anesthetized rat.
      Blockade of CeA attenuated the pressor response to microinjection of AngII into
      the BST. Eighty-six AngII microinjections were given into the BST and 198 single
      unit responses were recorded from CeA simultaneously, from which 89 showed a
      short duration excitatory response and 109 showed no responses. In conclusion,
      microinjection of AngII into the BST produces a short excitatory single unit
      response in the CeA, resulting in contribution of amygdala to the resulted
      pressor response. Taken together, our study and previous studies suggest a
      plausible hypothesis that these two nuclei perform their cardiovascular functions
      in cooperation with each other.

PMID- 27720814
TI  - Live imaging of inhibitory axons: Synapse formation as a dynamic trial-and-error
      process.
AB  - In this review I discuss recent live imaging studies that demonstrate that
      synapses, and in particular inhibitory synapses, are highly dynamic structures.
      The ongoing changes of presynaptic boutons within axons emphasize the stochastic
      aspect of inhibitory synapse formation and paint a picture of a dynamic trial-and
      error process. Furthermore, I discuss recent and previous insights in the
      molecular and mechanistic pathways that underlie synapse formation, with a
      specific focus on the formation of inhibitory presynaptic boutons.

PMID- 27720817
TI  - Microencapsulation of grape polyphenols using maltodextrin and gum arabic as two
      alternative coating materials: Development and characterization.
AB  - Phenolic compounds obtained from fruits have recently gained a great attention
      due to their bioactive roles. However, they are sensitive and they can be easily
      affected by physicochemical factors that create a great challenge to incorporate
      them into the food products. Hence, this work aimed to investigate
      microencapsulation of these compounds to provide a solution for this problem by
      improving their stability and protecting them against oxidation, light, moisture
      and temperature. A lab scale spray-dryer was chosen to produce microcapsules of
      polyphenols using different dextrose equivalents of maltodextrin and gum arabic
      as a coating material. Two different core: coating material ratios (1:1 and 1:2),
      three different maltodextrin: gum arabic ratios (10:0, 8:2 and 6:4), and four
      different inlet temperatures (120, 140, 160, 180 degrees C) were investigated.
      When all parameters (yields, hygroscopicity, total and surface phenolic contents,
      antioxidant activity, individual phenolic compounds and particle morphology) were
      evaluated; the most efficient microcapsules were obtained with an 8:2 ratio of
      maltodextrin: gum arabic at 140 degrees C inlet temperature. Microcapsules were
      also comprehensively studied and characterized using scanning electron microscopy
      (SEM) and high performance liquid chromatography (HPLC).

PMID- 27720816
TI  - Cytomegalovirus serostatus, inflammation, and antibody response to influenza
      vaccination in older adults: The moderating effect of beta blockade.
AB  - Cytomegalovirus (CMV) has been implicated as a factor in immunosenescence,
      including poor antibody response to vaccination and higher immune activation and
      inflammation. Some people may be more or less vulnerable to the negative effects
      of CMV. The present investigation tested the effects of beta-blocker use and
      chronological age on the associations between CMV and immunity in adults aged 60
      91 (N=98; 69% CMV seropositive) who were administered the trivalent influenza
      vaccine for up to 5years. Peak antibody response, corrected for baseline, and
      spring (persistent) antibody response, corrected for peak, were assessed, as well
      as beta-2 microglobulin (beta2MU) and interleukin-6 (IL-6). In multi-level models
      with years at Level 1 and people at Level 2, CMV serostatus did not predict peak
      antibody response, but there was a 3-way interaction between CMV serostatus, age,
      and beta-blockers. Age was negatively associated with peak antibody, but only
      among adults who were CMV seropositive and taking beta-blockers. CMV seronegative
      adults who were not taking beta-blockers had the highest antibody persistence.
      CMV serostatus was not associated with beta2MU or IL-6. Results suggest that CMV+
      serostatus may negatively compromise antibody response to a greater degree than
      inflammatory markers in older adults. Furthermore, older adults who take beta
      blockers may be more vulnerable to negative effects of age and CMV on peak
      antibody response, perhaps by virtue of their underlying health condition.

PMID- 27720818
TI  - SCT: Spinal Cord Toolbox, an open-source software for processing spinal cord MRI
      data.
AB  - For the past 25 years, the field of neuroimaging has witnessed the development of
      several software packages for processing multi-parametric magnetic resonance
      imaging (mpMRI) to study the brain. These software packages are now routinely
      used by researchers and clinicians, and have contributed to important
      breakthroughs for the understanding of brain anatomy and function. However, no
      software package exists to process mpMRI data of the spinal cord. Despite the
      numerous clinical needs for such advanced mpMRI protocols (multiple sclerosis,
      spinal cord injury, cervical spondylotic myelopathy, etc.), researchers have been
      developing specific tools that, while necessary, do not provide an integrative
      framework that is compatible with most usages and that is capable of reaching the
      community at large. This hinders cross-validation and the possibility to perform
      multi-center studies. In this study we introduce the Spinal Cord Toolbox (SCT), a
      comprehensive software dedicated to the processing of spinal cord MRI data. SCT
      builds on previously-validated methods and includes state-of-the-art MRI
      templates and atlases of the spinal cord, algorithms to segment and register new
      data to the templates, and motion correction methods for diffusion and functional
      time series. SCT is tailored towards standardization and automation of the
      processing pipeline, versatility, modularity, and it follows guidelines of
      software development and distribution. Preliminary applications of SCT cover a
      variety of studies, from cross-sectional area measures in large databases of
      patients, to the precise quantification of mpMRI metrics in specific spinal
      pathways. We anticipate that SCT will bring together the spinal cord neuroimaging
      community by establishing standard templates and analysis procedures.

PMID- 27720815
TI  - Toll-interacting protein deficiency promotes neurodegeneration via impeding
      autophagy completion in high-fat diet-fed ApoE-/- mouse model.
AB  - The excessive accumulation of specific cellular proteins or autophagic vacuoles
      (AVs) within neurons is a pathologic hallmark of neurodegenerative diseases.
      Constitutive autophagy in neurons prevents abnormal intracellular protein
      aggregation and is critical for maintaining cell survival. Since our previous
      study showed that Toll-interacting protein (Tollip)-deficient macrophages had
      constitutive disruption of endosome-lysosome fusion, we hypothesize that Tollip
      deficiency may also promote neuron death via blockage of autophagy completion.
      Indeed, we observed significantly higher levels of neuron death in the brain
      regions of cerebral cortex, hippocampus, and cerebellum from ApoE-/-/Tollip-/-
      mice as compared to ApoE-/- mice fed with high fat diet (HFD). We further
      documented diminished density of neurons and increased ratios of TUNEL positive
      cells in the hippocampus of ApoE-/-/Tollip-/- mice. The ultrastructural electron
      microscopy analyses revealed neuron cell shrinkage as well as loss of
      intracellular structure in brain tissues from ApoE-/-/Tollip-/- mice. There was
      dramatic accumulation of autophagosomes in the cytoplasm, elevated accumulation
      of beta-amyloid and alpha-synuclein, and increased levels of p62 and Parkin in
      the brain tissues from ApoE-/-/Tollip-/- mice as compared to ApoE-/- mice. Our
      data suggest that Tollip may play a crucial role in sustaining neuron health by
      facilitating the completion of autophagy, and that Tollip-deficiency may
      accelerate neuron death related to neurological disease such as Alzheimer's
      disease.

PMID- 27720820
TI  - The norepinephrine system and its relevance for multi-component behavior.
AB  - The ability to execute several actions in a specific temporal order to achieve an
      overarching goal, a process often termed action cascading or multi-component
      behavior, is essential for everyday life requirements. We are only at the
      beginning to understand the neurobiological mechanisms important for these
      cognitive processes. However, it is likely that the locus coeruleus
      norepinephrine (LC-NE) system may be of importance. In the current study we
      examine the relevance of the LC-NE system for action cascading processes using a
      system neurophysiological approach combining high-density EEG recordings and
      source localization to analyze event-related potentials (ERPs) with recordings of
      pupil diameter as a proximate of LC-NE system activity. N=25 healthy participants
      performed an action cascading stop-change paradigm. Integrating ERPs and pupil
      diameter using Pearson correlations, the results show that the LC-NE system is
      important for processes related to multi-component behavior. However, the LC-NE
      system does not seem to be important during the time period of response selection
      processes during multi-component behavior (reflected in the P3) as well as during
      perceptual and attentional selection (P1 and N1 ERPs). Rather, it seems that the
      neurophysiological processes in the fore period of a possibly upcoming imperative
      stimulus to initiate multi-component behavior are correlated with the LC-NE
      system. It seems that the LC-NE system facilitates responses to task-relevant
      processes and supports task-related decision and response selection processes by
      preparing cognitive control processes in case these are required during multi
      component behavior rather than modulating these processes once they are
      operating.

PMID- 27720819
TI  - Mapping white-matter functional organization at rest and during naturalistic
      visual perception.
AB  - Despite the wide applications of functional magnetic resonance imaging (fMRI) to
      mapping brain activation and connectivity in cortical gray matter, it has rarely
      been utilized to study white-matter functions. In this study, we investigated the
      spatiotemporal characteristics of fMRI data within the white matter acquired from
      humans both in the resting state and while watching a naturalistic movie. By
      using independent component analysis and hierarchical clustering, resting-state
      fMRI data in the white matter were de-noised and decomposed into spatially
      independent components, which were further assembled into hierarchically
      organized axonal fiber bundles. Interestingly, such components were partly
      reorganized during natural vision. Relative to resting state, the visual task
      specifically induced a stronger degree of temporal coherence within the optic
      radiations, as well as significant correlations between the optic radiations and
      multiple cortical visual networks. Therefore, fMRI contains rich functional
      information about the activity and connectivity within white matter at rest and
      during tasks, challenging the conventional practice of taking white-matter
      signals as noise or artifacts.

PMID- 27720822
TI  - Genetic basis for high population diversity in Protea-associated Knoxdaviesia.
AB  - Sexual reproduction is necessary to generate genetic diversity and, in ascomycete
      fungi, this process is controlled by a mating type (MAT) locus with two
      complementary idiomorphs. Knoxdaviesia capensis and K. proteae (Sordariomycetes;
      Microascales; Gondwanamycetaceae) are host-specific saprophytic fungi that show
      high population diversity within their Protea plant hosts in the Cape Floristic
      Region of South Africa. We hypothesise that this diversity is the result of
      outcrossing driven by a heterothallic mating system and sought to describe the
      MAT1 loci of both species. The available genome assembly of each isolate
      contained only one of the MAT1 idiomorphs necessary for sexual reproduction,
      implying that both species are heterothallic. Idiomorph segregation during
      meiosis, a 1:1 ratio of idiomorphs in natural populations and mating experiments
      also supported heterothallism as a sexual strategy. Long-range PCR and shot-gun
      sequencing to identify the opposite idiomorph in each species revealed no
      sequence similarity between MAT1-1 and MAT1-2 idiomorphs, but the homologous
      idiomorphs between the species were almost identical. The MAT1-1 idiomorph
      contained the characteristic MAT1-1-1 and MAT1-1-2 genes, whereas the MAT1-2
      idiomorph consisted of the genes MAT1-2-7 and MAT1-2-1. This gene content was
      similar to that of the three species in the Ceratocystidaceae (Microascales) with
      characterized MAT loci. The Knoxdaviesia MAT1-2-7 protein contained and alpha
      domain and predicted intron, which suggests that this gene arose from MAT1-1-1
      during a recombination event. In contrast to the Ceratocystidaceae species,
      Knoxdaviesia conformed to the ancestral Sordariomycete arrangement of flanking
      genes and is, therefore, a closer reflection of the structure of this locus in
      the Microascalean ancestor.

PMID- 27720821
TI  - Field strength dependence of grey matter R2* on venous oxygenation.
AB  - The relationship between venous blood oxygenation and change in transverse
      relaxation rate (DeltaR2*) plays a key role in calibrated BOLD fMRI. This
      relationship, defined by the parameter beta, has previously been determined using
      theoretical simulations and experimental measures. However, these earlier studies
      have been confounded by the change in venous cerebral blood volume (CBV) in
      response to functional tasks. This study used a double-echo gradient echo EPI
      scheme in conjunction with a graded isocapnic hyperoxic sequence to assess
      quantitatively the relationship between the fractional venous blood oxygenation
      (1-Yv) and transverse relaxation rate of grey matter (DeltaR2?GM*), without
      inducing a change in vCBV. The results demonstrate that the relationship between
      DeltaR2* and fractional venous oxygenation at all magnet field strengths studied
      was adequately described by a linear relationship. The gradient of this
      relationship did not increase monotonically with field strength, which may be
      attributed to the relative contributions of intravascular and extravascular
      signals which will vary with both field strength and blood oxygenation.

PMID- 27720824
TI  - Mechanisms of temperature sensitivity of attenuated Urabe mumps virus.
AB  - Temperature sensitivity is a phenotype often associated with attenuation of
      viruses. Previously, we purified several mumps variants from an incompletely
      attenuated Urabe strain live attenuated vaccine. Here we characterize one isolate
      that is sensitive to growth at high temperature. This virus was attenuated in a
      small animal model of mumps virulence, and we identified unique coding
      substitutions in the hemagglutinin-neuraminidase (HN), the viral polymerase (L)
      gene, and a non-coding substitution close to the anti-genome promoter sequences.
      At the non-permissive temperature, transcription of viral mRNAs and production of
      the replication intermediate were reduced compared to events at the permissive
      temperature and to a non-ts virulent Urabe virus. As well, synthesis of viral
      proteins was also reduced at the higher temperature. While the actual sequence
      substitutions in the ts virus were unique, the pattern of substitutions in HN, L
      and genome end sequences is similar to another attenuated Urabe virus previously
      described by us.

PMID- 27720823
TI  - Higher prevalence of cancer related mutations 1762T/1764A and PreS deletions in
      hepatitis B virus (HBV) isolated from HBV/HIV co-infected compared to HBV-mono
      infected Chinese adults.
AB  - In the era of combination therapy for human immunodeficiency virus (HIV), liver
      disease including hepatocellular carcinoma (HCC), are the major causes of death
      for patients co-infected with hepatitis B virus (HBV) and HIV. However, the
      mechanisms remain obscure. We aimed to determine whether HCC-related HBV
      mutations including 1762T/1764A double mutation and pre-S deletions occur more
      frequently in HBV/HIV co-infected individuals compared to HBV mono-infected
      individuals. In this study, the basic core promoter (BCP) and the preS/S regions
      of HBV isolated from 61 pairs of HBV/HIV co-infected and HBV mono-infected
      participants were analyzed. We found that the prevalence of HBV isolates with
      1762T/1764A and/or preS deletion mutations was 37.7% (95% CI: 29.1-46.3). The
      prevalence of these mutations in HBV/HIV co-infected group (52.5%, 95% CI: 40.0
      65.0) was significantly higher than in the HBV mono-infected group (23.0%, 95%
      CI: 12.4-33.6) (X2=11.307, P<0.05). HBV/HIV co-infection was associated with
      higher viral loads but these higher viral loads were not associated with the
      higher prevalence of HCC-related HBV mutations. Individually 1762T1764A (44.3%)
      or preS deletions (23%) occurred more frequently in isolates from co-infected
      compared to mono-infected individuals (21.3%, 4.9%, respectively) (X2=7.290,
      P<0.05; X2=8.270, P<0.05). Moreover, 1762T/1764A and preS deletions occurred more
      frequently in genotypes C and I compared to genotype B (p<0.05). Multivariate
      analysis revealed that co-infection with HIV was associated with the development
      of both 1762T/1764A ((RR: 2.932(1.325-6.488)) and preS deletions ((RR:
      5.759(1.562-21.235)). These results demonstrate that co-infection with HIV was
      associated with increased prevalence of HCC-related mutations in HBV isolates
      from Chinese patients.

PMID- 27720825
TI  - Importance of latency and amplitude values of recurrent laryngeal nerve during
      thyroidectomy in diabetic patients.
AB  - BACKGROUND: Diabetes mellitus may cause degeneration in the myelin and/or axonal
      structures of peripheral nerves. The aim of this study was to investigate the
      effects of diabetic neuropathy on intraoperative neuromonitoring findings such as
      latency and amplitude values of the recurrent laryngeal nerves during
      thyroidectomy. To our knowledge this is the first study to report comparison of
      the electrophysiologic features of diabetic and non-diabetic patients. MATERIALS
      AND METHODS: One-hundred-and-eleven consecutive patients who received
      neuromonitoring during thyroidectomy between 2013 and 2015 were included to
      study. The patients were divided into two groups according to the presence of
      diabetes mellitus. Pre-thyroidectomy and post thyroidectomy motor response
      latency and amplitude values of recurrent laryngeal nerves were compared between
      groups. Neuromonitoring findings, demographic data and postoperative
      complications were evaluated. RESULTS: The diabetic group consisted of 29 (26.1%)
      patients while 82 (73.9%) patients were in non-diabetic group. The mean post
      thyroidectomy amplitude values (millivolts-mV) of the recurrent laryngeal nerve
      were significantly lower in diabetic group (0.51 +/- 0.26 mV vs. 0,70 +/- 0,46
      mV, p < 0.05), whereas the latency values were significantly higher (2.50 +/-
      0.86 ms vs. 1.85 +/- 0.59 ms, p < 0.01) compared to non-diabetic group.
      Additionally, post-thyroidectomy latency values were significantly increased
      compared to the pre-thyroidectomy latency values (2.50 +/- 0.86 ms vs. 2.02 +/-
      0.43 ms) in diabetic group patients (p < 0.05). Although postoperative
      complication rates were higher in diabetic group (10.3% vs. 5.9%), there were no
      statistical significance differences. CONCLUSIONS: Prolonged latency and
      decreased amplitude values in recurrent laryngeal nerves of diabetic patients
      show that diabetic neuropathy of the recurrent laryngeal nerves develop similarly
      to the peripheral nerves. Increased post-thyroidectomy latency values reveal that
      the recurrent laryngeal nerve is more susceptible to surgical trauma in diabetic
      patients.

PMID- 27720826
TI  - The Ciona intestinalis cleavage clock is independent of DNA methylation.
AB  - The initiation of embryonic gene expression in ascidian embryos appears to be
      tightly regulated by the number of DNA replication cycles. DNA methylation is
      thought to contribute to the clock mechanism that counts the rounds of DNA
      replication. We used mass spectrometry and whole genome bisulfite sequencing to
      characterize DNA methylation changes that occur in early developmental stages of
      the ascidian, Ciona intestinalis. We found that global DNA methylation in early
      Ciona development was static, and a base-wise comparison between the genomes of
      consecutive developmental stages found no DNA demethylation that was related to
      zygotic gene activation. Additionally, 5hmC was hardly detected by mass
      spectrometry in the developmental samples, suggesting a lack of demethylation
      mediated by ten eleven translocation (TET) methylcytosine dioxygenase in C.
      intestinalis. We conclude that DNA methylation is not involved in regulating DNA
      replication-dependent transcriptional activation.

PMID- 27720827
TI  - Timing of Surgery after Neoadjuvant Chemoradiation in Locally Advanced Non-Small
      Cell Lung Cancer.
AB  - INTRODUCTION: A subset of patients with potentially resectable clinical stage
      IIIA NSCLC are managed with trimodality therapy. However, little data exist to
      guide the timing of surgery after neoadjuvant therapy. This study examined
      whether the time interval between neoadjuvant chemoradiation (NCRT) and surgical
      resection affects overall survival. METHODS: Patients with clinical stage IIIA
      disease (T1-3 N2) NSCLC who underwent NCRT were identified in the National Cancer
      Data Base (NCDB) between 2004 and 2012 and categorized on the basis of the
      interval between chemoradiation and surgery (0 to <=3, >3 to <=6, >6 to <=9, and
      >9 to <=12 weeks). Other clinical stages were excluded. The Kaplan-Meier method
      and log-rank tests were used to compare overall survival rates, and a
      bootstrapped Cox proportional hazards model was used to determine significant
      contributors to overall survival. RESULTS: Of the 1623 patients identified, 7.9%
      underwent an operation 0 to 3 weeks or less after NCRT, 50.5% underwent an
      operation greater than 3 and less than or equal to 6 weeks after NCRT, 31.9%
      underwent an operation greater than 6 and less than or equal to 9 weeks after
      NCRT, and 9.6% underwent an operation greater than 9 and less than or equal to 12
      weeks after NCRT. Multivariate survival analysis demonstrated no significant
      difference in survival in those who underwent an operation within 6 weeks of
      NCRT. However, significant drops in overall survival were observed in those who
      had an operation greater than 6 and less than or equal to 9 weeks after NCRT
      (hazard ratio = 1.33, 95% confidence interval: 1.01-1.76, p = 0.043) and greater
      than 9 and less than or equal to 12 weeks after NCRT (hazard ratio = 1.44, 95%
      confidence interval: 1.04-2.01, p = 0.030). CONCLUSIONS: The findings from this
      retrospective study suggest that overall survival may be significantly lower in
      patients with clinical stage IIIA N2 NSCLC who undergo an operation later than 6
      weeks after NCRT. These results discourage unnecessary delays in surgery.

PMID- 27720828
TI  - Wild type agr-negative livestock-associated MRSA exhibits high adhesive capacity
      to human and porcine cells.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes
      of nosocomial infections and a major public health concern worldwide. During the
      last decade, MRSA of CC398 have emerged as important colonizers of livestock.
      These strains also represent an increasing cause of human infections. A recent
      study reporting a new dominant spa type among MRSA from Finish fattening pigs
      (CC398/t2741) identified a strain lacking both the global virulence regulator
      gene locus agr and the adhesion gene fnbB. The aim of this study was to
      characterize this agr/fnbB-negative livestock-associated MRSA strain in terms of
      growth, hemolysis and adhesive capacity, and to provide data on its genomic
      background. To this end, growth curves and hemolysis patterns were generated and
      adhesion assays on human keratinocyte and porcine nasal mucosa cell lines were
      performed. Whole genome sequencing was used to determine the nature and extent of
      the relevant deletions in the livestock strains. For comparison, an agr-positive,
      fnbB-negative CC398/t2741 strain from the same pig herd, an agr/fnbB- positive
      CC398/t034 strain from another pig herd and one human MRSA strain and its
      isogenic Deltaagr knockout mutant were used. The agr-negative strains adhered
      significantly better to human and porcine host cells than the agr-positive
      control strains. For the agr-positive porcine MRSA strains, cytotoxic effects on
      porcine mucosal cells were observed. The strong adhesive capacity of the
      naturally agr-negative livestock-associated MRSA, in combination with diminished
      cytotoxic effects, is likely favorable for inducing persistent colonization in
      pigs. Independently of the host cell type, similar adhesive capacities of the
      naturally agr-negative livestock-associated MRSA and the human MRSA strain were
      shown. Our results indicate that loss of agr in the livestock-associated MRSA
      strain investigated in this study may have increased its potential to be
      transmitted to and amongst humans.

PMID- 27720829
TI  - The SULSA Assay Development Fund: accelerating translation of new biology from
      academia to pharma.
AB  - With industry increasingly sourcing preclinical drug discovery projects from
      academia it is important that new academic discoveries are enabled through
      translation with HTS-ready assays. However, many scientifically interesting,
      novel molecular targets lack associated high-quality, robust assays suitable for
      hit finding and development. To bridge this gap, the Scottish Universities Life
      Sciences Alliance (SULSA) established a fund to develop assays to meet quality
      criteria such as those of the European Lead Factory. A diverse project portfolio
      was quickly assembled, and a review of the learnings and successful outcomes
      showed this fund as a new highly cost-effective model for leveraging significant
      follow-on resources, training early-career scientists and establishing a culture
      of translational drug discovery in the academic community.

PMID- 27720830
TI  - Transcriptome analysis of the responses to methyl methanesulfonate treatment in
      mouse pachytene spermatocytes and round spermatids.
AB  - Spermatogenesis is threatened by DNA alkylating agents, one major category of DNA
      damaging agents. Currently, little is known about the alterations in
      transcriptome profiling of the mouse spermatogenic cells in response to DNA
      alkylation at distinct stages of spermatogenesis. In this study, RNA sequencing
      (RNA-seq) was performed in pachytene spermatocytes (PS) and round spermatids (RS)
      at 0 or 30min following Methyl Methanesulfonate (MMS) treatment and with
      untreated controls. A large number of differentially expressed genes (DEGs) were
      identified by comparison of the three groups in PS and RS, respectively.
      Functional analyses of all DEGs highlighted the protein ubiquitination pathway
      and DNA damage response (DDR) network being the two main biological processes in
      common in the two cell types. Further analyses of the DEGs with 2-fold or more
      changes between 30min repair and control group indicated that several cytokine
      signaling pathways were the most strongly affected in PS and DDR related pathways
      in RS, respectively. Gene ontology (GO) analyses directly showed differential
      biological process (BP) affected between PS and RS, with "regulation of
      transcription" being most overrepresented in PS and "cellular response to stress"
      in RS, respectively. Moreover, 374 DDR-related genes in PS and 158 in RS among
      all DEGs were filtered and clustered, which showed dynamic expression patterns in
      PS and RS. Our analyses provide a transcriptional landscape for male germ cells
      in response to MMS during spermatogenesis.

PMID- 27720831
TI  - Imaging flow cytometry in the assessment of leukocyte-platelet aggregates.
AB  - Platelets are subcellular blood elements with a well-established role in
      haemostasis. Upon activation platelets undergo granule exocytosis, resulting in
      alpha-granule P-Selectin being expressed on the cell membrane. This allows
      binding of activated platelets to P-Selectin glycoprotein ligand 1 (PSGL-1)
      expressing leukocytes, forming leukocyte-platelet aggregates (LPAs). Whole blood
      flow cytometry (FCM) has demonstrated that elevated circulating LPAs (especially
      monocyte LPAs) are linked to atherothrombosis in high risk patients, and that
      activated platelet binding influences monocytes towards a pro-adhesive and pro
      atherogenic phenotype. However, a limitation of conventional FCM is the potential
      for coincident events to resemble LPAs despite no tethering. Imaging cytometry
      can be used to characterize LPA formation and distinguish circulating MPAs from
      coincidental events. Platelets and leukocyte subsets are identified by expression
      of surface markers (e.g. the lipopolysachharide receptor CD14 on monocytes,
      glycoprotein Ib CD42b on platelets). In conventional FCM, all events with both
      leukocyte and platelet characteristics are designated as LPAs. However, by using
      an 'internal' mask based on the brightfield image and the fluorescent platelet
      identifier, imaging flow cytometry is able to distinguish leukocytes with
      tethered platelets (genuine LPAs) from leukocyte with coincidental, untethered
      platelets nearby. Mechanisms (e.g. adhesion molecules) or consequences (e.g.
      signal transduction) can then be separately analysed in platelet tethered and
      untethered leukocytes. Imaging flow cytometry therefore provides a more accurate
      approach for both enumeration and analysis of LPAs than conventional FCM.

PMID- 27720833
TI  - Not just lip service: The lifesaving role of telephone CPR.

PMID- 27720834
TI  - Witness status: A new definition for out-of-hospital cardiac arrest?

PMID- 27720832
TI  - Effects of renal sympathetic denervation on the stellate ganglion and brain stem
      in dogs.
AB  - BACKGROUND: Renal sympathetic denervation (RD) is a promising method of
      neuromodulation for the management of cardiac arrhythmia. OBJECTIVE: We tested
      the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces
      the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion
      (SG) and brain stem. METHODS: We implanted a radiotransmitter to record SGNA and
      electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery
      for RD and 2 months SGNA recording. Cell death was probed by terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS:
      Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 +/- 4.0, 9.3 +/
      2.8, and 9.6 +/- 2.0 MUV, respectively (P = .042). The SG from RD but not normal
      control dogs (n = 5) showed confluent damage. An average of 41% +/- 10% and 40%
      +/- 16% of ganglion cells in the left and right SG, respectively, were TUNEL
      positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The
      left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion
      cells than did the left SG of control dogs (P = .028 and P = .047, respectively).
      Extensive TUNEL-positive neurons and glial cells were also noted in the medulla,
      associated with strongly positive glial fibrillary acidic protein staining. The
      distribution was heterogeneous, with more cell death in the medial than lateral
      aspects of the medulla. CONCLUSION: Bilateral RD caused significant central and
      peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs.
      These findings may in part explain the antiarrhythmic effects of RD.

PMID- 27720835
TI  - Variation of fermentation redox potential during cell-recycling continuous
      ethanol operation.
AB  - Fermentation redox potential was monitored during cell-recycling continuous
      ethanol operation. The cell-recycling system (CRS) was operated using two hollow
      fibre (HF) membranes (pore sizes 0.20 and 0.65MUm) at three dilution rates (0.02,
      0.04 and 0.08h-1). Saccharomyces cerevisiae NP 01 were recycled in the fermenter
      at a recycle ratio of 0.625. Aeration was provided at 2.5vvm for the first 4h and
      then further supplied continuously at 0.25vvm. As steady state was established,
      results showed that the fermentation redox potential was lower for processes
      employing CRS than those without. At the same dilution rates, the sugar
      utilization and ethanol production with CRS were higher than those without CRS.
      The highest fermentation efficiency (87.94g/l of ethanol, ~90% of theoretical
      yield) was achieved using a 0.2-MUm HF membrane CRS at a dilution rate of 0.02h
      1. It was found that 7.53-10.07% of the carbon derived from glucose was
      incorporated into the yeast. Further, at the same dilution rates, yeast in the
      processes with CRS incorporated less carbon into ethanol than in those grown
      without CRS. This result suggests that processes involving CRS utilize more
      carbon for metabolite synthesis than biomass formation. This indicated that the
      processes with CRS could utilize more carbon for metabolite synthesis than
      biomass formation.

PMID- 27720836
TI  - Nitrosothiol formation and S-nitrosation signaling through nitric oxide
      synthases.
AB  - Nitric oxide (NO) is a gaseous signaling molecule impacting many biological
      pathways. NO is produced in mammals by three nitric oxide synthase (NOS)
      isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). nNOS and
      eNOS produce low concentrations of NO for paracrine signaling; NO produced and
      released from one cell diffuses to a neighboring cell where it binds and
      activates soluble guanylyl cyclase (sGC). iNOS produces high concentrations of NO
      using NO toxicity to amplify the innate immune response. Recent work has also
      defined protein cysteine S-nitrosation as a pathway of sGC-independent NO
      signaling. Though many studies have shown that S-nitrosation regulates the
      activity of NOS isoforms and other proteins in vivo, many issues need to be
      resolved to establish S-nitrosation as a viable signaling mechanism. Several
      chemical mechanisms result in S-nitrosation including transition metal-catalyzed
      pathways, NO oxidation followed by thiolate reaction, and thiyl radical
      recombination with NO. Once formed, nitrosothiols can be transferred between
      cellular cysteine residues via transnitrosation reactions. However, it is largely
      unclear how these chemical processes result in selective S-nitrosation of
      specific cellular cysteine residues. S-nitrosation site selectivity may be
      imparted via direct interactions or colocalization with NOS isoforms that focus
      chemical or transnitrosation mechanisms of nitrosothiol formation or transfer.
      Here, we discuss chemical mechanisms of nitrosothiol formation, S-nitrosation of
      NOS isoforms, and potential S-nitrosation signaling cascades resulting from NOS S
      nitrosation.

PMID- 27720837
TI  - Subunit analysis of mitochondrial cytochrome c oxidase and cytochrome bc1 by
      reversed-phase high-performance liquid chromatography.
AB  - A rapid separation of the ten nuclearly-encoded subunits of mitochondrial
      cytochrome c oxidase, and ten out of the eleven subunits of cytochrome bc1, was
      achieved using a short, 50 mm C18-reversed-phase column. The short column
      decreased the elution time 4-7 fold while maintaining the same resolution
      quality. Elution was similar to a previously published protocol, i.e., a
      water/acetonitrile elution gradient containing trifluoroacetic acid. Isolated
      subunits were identified by MALDI-TOF. The rapidity of the described method makes
      it extremely useful for determining the subunit composition of isolated
      mitochondrial complexes. The method can be used for both analytical and micro
      preparative purposes.

PMID- 27720838
TI  - Effectiveness of Elbasvir and Grazoprevir Combination, With or Without Ribavirin,
      for Treatment-Experienced Patients With Chronic Hepatitis C Infection.
AB  - BACKGROUND & AIMS: Patients infected with hepatitis C virus (HCV) genotype 1, 4,
      or 6, with or without cirrhosis, previously treated with peg-interferon and
      ribavirin, are a challenge to treat. We performed a phase 3 randomized controlled
      open-label trial to assess the effects of 12 or 16 weeks of treatment with once
      daily elbasvir (an HCV NS5A inhibitor, 50 mg) and grazoprevir (an HCV NS3/4A
      protease inhibitor, 100 mg), in a fixed-dose combination tablet, with or without
      twice-daily ribavirin, in this patient population. METHODS: We analyzed data from
      420 patients (35% with cirrhosis, 64% with a null or partial response to peg
      interferon and ribavirin) who were randomly assigned (1:1:1:1) to groups given
      elbasvir and grazoprevir once daily, with or without twice-daily ribavirin, for
      12 or 16 weeks, at 65 study centers in 15 countries in Europe, Asia, and Central
      and North America. Randomization was stratified by cirrhosis status and type of
      peg-interferon and ribavirin treatment failure. HCV RNA was measured using COBAS
      TaqMan v2.0. The primary end point was HCV RNA <15 IU/mL, 12 weeks after
      completion of treatment (SVR12). We aimed to determine whether the proportion of
      patients achieving an SVR12 in any group was greater than the reference rate
      (58%). RESULTS: With 12 weeks of treatment, an SVR12 was achieved by 92.4% of
      patients given elbasvir and grazoprevir and 94.2% of patients given elbasvir and
      grazoprevir with ribavirin. With 16 weeks of treatment, an SVR12 was achieved by
      92.4% of patients given elbasvir and grazoprevir and 98.1% of patients given
      elbasvir and grazoprevir with ribavirin. Among patients treated for 12 weeks
      without ribavirin, virologic failure occurred in 6.8%, 0%, and 12.5% of patients
      with HCV genotype 1a, 1b, or 4 infection, respectively. Among patients given
      elbasvir and grazoprevir for 12 weeks, virologic failure occurred in 0% of
      patients infected with HCV genotypes 1 and 4 who relapsed after completing peg
      interferon and ribavirin, and 7.5% infected with HCV genotypes 1 and 4,
      respectively, with a null or partial response to peg-interferon and ribavirin.
      Among patients treated for 16 weeks who received ribavirin, there were no
      incidences of virologic failure. Common adverse events were fatigue (23.1%),
      headache (19.8%), and nausea (11.0%). CONCLUSIONS: The combination tablet of
      elbasvir and grazoprevir, with or without ribavirin, was highly efficacious in
      inducing an SVR12 in patients with HCV genotype 1, 4, or 6 infection failed by
      previous treatment with peg-interferon and ribavirin, including patients with
      cirrhosis and/or a prior null response. The treatment was generally well
      tolerated. ClinicalTrials.gov Number: NCT02105701.

PMID- 27720841
TI  - Linking gene regulation to cell behaviors in the posterior growth zone of
      sequentially segmenting arthropods.
AB  - Virtually all arthropods all arthropods add their body segments sequentially, one
      by one in an anterior to posterior progression. That process requires not only
      segment specification but typically growth and elongation. Here we review the
      functions of some of the key genes that regulate segmentation: Wnt, caudal, Notch
      pathway, and pair-rule genes, and discuss what can be inferred about their
      evolution. We focus on how these regulatory factors are integrated with growth
      and elongation and discuss the importance and challenges of baseline measures of
      growth and elongation. We emphasize a perspective that integrates the genetic
      regulation of segment patterning with the cellular mechanisms of growth and
      elongation.

PMID- 27720840
TI  - Management Strategies to Improve Outcomes of Patients With Inflammatory Bowel
      Diseases.
AB  - Strategies for management of inflammatory bowel diseases are shifting from simple
      control of symptoms toward full control of these diseases (clinical and
      endoscopic remission), with the final aim of blocking their progression and
      preventing bowel damage and disability. New goals have been proposed for
      treatment, such as treat to target and tight control based on therapeutic
      monitoring and early intervention. For patients who achieve clinical remission,
      there is often interest in discontinuation of therapy due to safety or economic
      concerns. We review the evidence supporting these emerging paradigms, the reasons
      that early effective treatment can alter progression of inflammatory bowel
      diseases, the importance of examining objective signs of inflammation, and the
      safety of reducing treatment dosage. We also discuss recent findings regarding
      personalization of care, including factors that predict patient outcomes and
      response to therapies, as well as preventative strategies.

PMID- 27720842
TI  - Redox sensitivity of the MyD88 immune signaling adapter.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) mediates expression of
      key genes involved in innate immunity and inflammation. NF-kappaB activation has
      been repeatedly reported to be modulated by hydrogen peroxide (H2O2). Here, we
      show that the NF-kappaB-activating signaling adapter myeloid differentiation
      primary response gene 88 (MyD88) is highly sensitive to oxidation by H2O2 and may
      be redox-regulated in its function, thus facilitating an influence of H2O2 on the
      NF-kappaB signaling pathway. Upon oxidation, MyD88 forms distinct disulfide
      linked conjugates which are reduced by the MyD88-interacting oxidoreductase
      nucleoredoxin (Nrx). MyD88 cysteine residues functionally modulate MyD88
      dependent NF-kappaB activation, suggesting a link between MyD88 thiol oxidation
      state and immune signaling.

PMID- 27720843
TI  - Hospital-Based Health Care After Traumatic Brain Injury.
AB  - OBJECTIVE: To investigate trends of hospital-based health care utilization after
      admission to a level I trauma center after acute traumatic brain injury (TBI).
      DESIGN: Retrospective review. SETTING: Large urban trauma hospital and a hospital
      council data registry consisting of 88 member institutions (>150 hospitals)
      covering 15,000 square miles. PARTICIPANTS: All patients (N=5291) admitted to a
      level I trauma center between January 1, 2006, and June 30, 2014, who experienced
      an acute TBI based on International Classification of Diseases, Ninth Revision
      coding. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Included the
      incidence and type of select hospital-based services received. Analyses were also
      categorized based on demographic and injury-related information. RESULTS: Of the
      5291 patients with newly acquired TBI who were admitted, 512 died, leaving 4779
      patients for inclusion in the final analysis. Additional health care utilization
      from January 1, 2006, and June 30, 2014, was recorded for 3158 patients (66%),
      totaling 12,307 encounters, with a median of 3 encounters (interquartile range, 1
      5) and a maximum of 102 encounters. Most nonadmission urgent or procedural visits
      (96%) and inpatient encounters (93%) occurred in the first year. Of all the
      additional encounters, 9769 visits were nonadmission urgent or procedural visits
      (79%) with a median charge of $1955. The most common type of encounter was
      elective (46%), followed by medical emergency (29%). Of the remaining 2538
      inpatient encounters (21%), the mean length of stay was 6 days with a median
      charge of $28,450. Medical emergency (39%) and elective admissions (33%) again
      were the most common encounter type. CONCLUSIONS: This analysis encompasses
      health care utilization across the range of TBI severity and numerous hospital
      systems, allowing for a more comprehensive and objective identification of
      reasons for readmission. This represents an initial step to developing a
      preventive intervention to manage secondary complications postinjury.

PMID- 27720844
TI  - Arogenate Dehydratase Isoforms Differentially Regulate Anthocyanin Biosynthesis
      in Arabidopsis thaliana.
AB  - Anthocyanins, a group of L-phenylalanine (Phe)-derived flavonoids, have been
      demonstrated to play important roles in plant stress resistance and interactions
      between plants and insects. Although the anthocyanin biosynthetic pathway and its
      regulatory mechanisms have been extensively studied, it remains unclear whether
      the level of Phe supply affects anthocyanin biosynthesis. Here, we investigated
      the roles of arogenate dehydratases (ADTs), the key enzymes that catalyze the
      conversion of arogenate into Phe, in sucrose-induced anthocyanin biosynthesis in
      Arabidopsis. Genetic analysis showed that all six ADT isoforms function
      redundantly in anthocyanin biosynthesis but have differential contributions. ADT2
      contributes the most to anthocyanin accumulation, followed by ADT1 and ADT3, and
      ADT4-ADT6. We found that anthocyanin content is positively correlated with the
      levels of Phe and sucrose-induced ADT transcripts in seedlings. Consistently,
      addition of Phe to the medium could dramatically increase anthocyanin content in
      the wild-type plants and rescue the phenotype of the adt1 adt3 double mutant
      regarding the anthocyanin accumulation. Moreover, transgenic plants
      overexpressing ADT4, which appears to be less sensitive to Phe than
      overexpression of ADT2, hyperaccumulate Phe and produce elevated level of
      anthocyanins. Taken together, our results suggest that the level of Phe is an
      important regulatory factor for sustaining anthocyanin biosynthesis.

PMID- 27720839
TI  - Mechanisms, Management, and Treatment of Fibrosis in Patients With Inflammatory
      Bowel Diseases.
AB  - In the last 10 years, we have learned much about the pathogenesis, diagnosis, and
      management of intestinal fibrosis in patients with inflammatory bowel diseases.
      Just a decade ago, intestinal strictures were considered to be an inevitable
      consequence of long-term inflammation in patients who did not respond to anti
      inflammatory therapies. Inflammatory bowel diseases-associated fibrosis was seen
      as an irreversible process that frequently led to intestinal obstructions
      requiring surgical intervention. This paradigm has changed rapidly, due to the
      antifibrotic approaches that may become available. We review the mechanisms and
      diagnosis of this serious complication of inflammatory bowel diseases, as well as
      factors that predict its progression and management strategies.

PMID- 27720845
TI  - Identification of a gene expression signature in peripheral blood of multiple
      sclerosis patients treated with disease-modifying therapies.
AB  - Multiple Sclerosis (MS) is an inflammatory disease with neurodegenerative
      alterations, ultimately progressing to neurological handicap. Therapies are
      effective in counteracting inflammation but not neurodegeneration. Biomarkers
      predicting disease course or treatment response are lacking. We investigated
      whether altered gene and protein expression profiles were detectable in the
      peripheral blood of 78 relapsing remitting MS (RR-MS) patients treated by disease
      modifying therapies. A discovery/validation study on RR-MS responsive to
      glatiramer acetate identified 8 differentially expressed genes: ITGA2B, ITGB3,
      CD177, IGJ, IL5RA, MMP8, P2RY12, and S100beta. A longitudinal study on glatiramer
      acetate, Interferon-beta, or Fingolimod treated RR-MS patients confirmed that 7
      out of 8 genes were downregulated with reference to the different therapies,
      whereas S100beta was always upregulated. Thus, we identified a peripheral gene
      signature associated with positive response in RR-MS which may also explain drug
      immunomodulatory effects. The usefulness of this signature as a biomarker needs
      confirmation on larger series of patients.

PMID- 27720846
TI  - Successful treatment of palmoplantar pustulosis with rheumatoid arthritis, with
      tofacitinib: Impact of this JAK inhibitor on T-cell differentiation.

PMID- 27720847
TI  - Extraction, characterization and evaluation of Kaempferia galanga L.
      (Zingiberaceae) rhizome extracts against acute and chronic inflammation in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The rhizomes of an acaulescent perennial herb,
      Kaempferia galanga Linn (Family: Zingiberaceae), used as traditional ayurvedic
      herb to get relief from indigestion, swelling, pain, high blood pressure and
      dyslipidemia. AIM OF THE STUDY: To prepare and characterize various extracts of
      Kaempferia galanga (K. galanga) for their comparative evaluation for the
      identification of the most efficacious extract and its possible pharmacological
      implication in acute and chronic inflammatory paradigm. MATERIALS AND METHODS:
      Dried and powdered rhizome of K. galanga was subjected to alcoholic extraction as
      well as successive extractions with various solvents. After phytochemical
      characterization, all the extracts were standardized for the presence of ethyl-p
      methoxycinnamate. The extracts, and the isolated compound, were tested against
      carrageenan-induced acute inflammation in rats. The most promising extract was
      tested against adjuvant-induced chronic inflammation in rats. Further, local
      myeloperoxidase (MPO) levels were investigated to establish the possible
      mechanism of action. RESULTS: Among the extracts, petroleum ether extract (SKG-1)
      and crude alcoholic extract (KG) had the maximum quantity of ethyl-p
      methoxycinnamate. SKG-1 (300mg/kg) was found effective against acute inflammation
      in rats. Further, SKG-1 (100mg/kg) reversed the inflammation and elevated MPO
      levels found in the chronic model. CONCLUSIONS: The results suggest that among
      all the extracts of K. galanga, SKG-1 effectively suppresses the progression of
      acute and chronic inflammation in rats by inhibition of neutrophil infiltration.

PMID- 27720849
TI  - Beneficial effect of commercial Rhodiola extract in rats with scopolamine-induced
      memory impairment on active avoidance.
AB  - : Rhodiola rosea L., family Crassulaceae also known as Golden Root or Arctic root
      is one of the most widely used medicinal plants with effect on cognitive
      dysfunction, psychological stress and depression. The aim of the study was to
      examine the effect of a standardized commercial Rhodiola extract on learning and
      memory processes in naive rats as well as its effects in rats with scopolamine
      induced memory impairment. MATERIALS AND METHODS: Sixty male Wistar rats were
      used in the study. The experiment was conducted in two series - on naive rats and
      on rats with scopolamine-induced model of impaired memory. The active avoidance
      test was performed in an automatic conventional shuttle box set-up. The criteria
      used were the number of conditional stimuli (avoidances), the number of
      unconditioned stimuli (escapes) as well as the number of intertrial crossings.
      RESULTS: The chemical fingerprinting of the standardized commercial Rhodiola
      extract was performed by means of nuclear magnetic resonance (NMR). Naive rats
      treated with standardized Rhodiola extract increased the number of avoidances
      during the learning session and memory retention test compared to the controls.
      Rats with scopolamine-induced memory impairment treated with Rhodiola extract
      showed an increase in the number of avoidances during the learning session and on
      the memory tests compared to the scopolamine group. The other two parameters were
      not changed in rats treated with the extract of Rhodiola in the two series.
      CONCLUSION: It was found that the studied Rhodiola extract exerts a beneficial
      effect on learning and memory processes in naive rats and rats with scopolamine
      induced memory impairment. The observed effect is probably due to multiple
      underlying mechanisms including its modulating effect on acetylcholine levels in
      the brain and MAO-inhibitory activity leading to stimulation of the monoamines'
      neurotransmission. In addition the pronounced stress-protective properties of
      Rhodiola rosea L. could also play a role in the improvement of cognitive
      functions.

PMID- 27720848
TI  - Evaluation of anti-hypertensive activity of Ulmus wallichiana extract and
      fraction in SHR, DOCA-salt- and L-NAME-induced hypertensive rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus wallichiana Planchon (Himalayan Elm), a
      traditional medicinal plant, used in fracture healing in folk tradition of
      Uttarakhand, Himalaya, India. It is also used as diuretic. U. rhynchophylla,
      native to China, known as Gou Teng in Chinese medicine, is used for hypertension
      (WHO). U. macrocarpa has antihypertensive and vasorelaxant activity. However, no
      detailed studies related to hypertension have been reported previously, so we
      have explored the antihypertensive activity of U. wallichiana. AIM OF THE STUDY:
      To investigate the pharmacological effect of ethanolic extract (EE) and butanolic
      fraction (BF) of U. wallichiana in hypertensive rats. MATERIALS AND METHODS: SHR,
      DOCA-salt- and L-NAME-induced hypertension models were used. Treatment was
      performed by oral administration of EE and BF of U. wallichiana (500mg/kg/day and
      50mg/kg/day) for 14 days. Then blood pressure was measured by non-invasive blood
      pressure (NIBP) measurement technique. Invasive blood pressure (IBP) was also
      reported to support the NIBP data. Concentrations of plasma renin, angiotensin II
      (Ang II), nitrate/nitrite (NO), cGMP were estimated. Angiotensin-converting
      enzyme (ACE) activity and ROS activity were also estimated. RESULTS: Blood
      pressure was significantly higher in SHR as compared to normotensive wistar group
      (170.59+/-0.83mmHg vs 121.54+/-1.24mmHg, respectively). SBP was increased in DOCA
      salt induced group compared to their control (132.77+/-3.90mmHg vs 107.85+/
      5.95mmHg, respectively) and L-NAME-induced group compared to their control
      (168.55+/-5.07mmHg vs 113.03+/-4.13mmHg, respectively). The treatment of extract
      and fraction of U. wallichiana significantly decreased the blood pressure in
      SHR+EE (151.26+/-1.85mmHg, p<0.001), SHR+BF (140.44+/-1.16mmHg, p<0.001); DOCA+EE
      (113.43+/-5.44mmHg, p<0.05), DOCA+BF (105.09+/-5.12mmHg, p<0.05) and L-NAME+EE
      (119.76+/-4.39mmHg, p<0.001), L-NAME+BF (117.50+/-7.27mmHg, p<0.001) compared to
      their respective diseased control groups. The plasma renin, Ang II and ACE
      activity were also significantly decreased and augmented the NO and cGMP levels.
      It also down regulated the expression of Renin, ACE, NOS3 and TGF-beta1 at mRNA
      levels. CONCLUSIONS: The EE and BF probably reducing the BP via Renin-angiotensin
      aldosterone system and NO/cGMP signaling pathway. The decrease in blood pressure
      may be due to presence of quercetin analogue flavonoids (2S,3S)-(+)-3',4',5,7
      tetrahydroxydihydroflavonol-6-C-beta-D-glucopyranoside; 6-Glucopyranosyl
      3,3',4',5,7-pentahydroxyflavone; 6-Glucopyranosyl-4',5,7-trihydroxyflavanone and
      (2S,3S)-(+)-4',5,7-trihydroxydihydroflavonol-6-C-beta-D-glucopyranoside, may be
      due to its antioxidant activity. Thus EE and BF of U. wallichiana found to have
      the potential ability to be used as herbal medicament to treat hypertension.

PMID- 27720850
TI  - An optimized protocol for adenosine triphosphate quantification in T lymphocytes
      of lymphopenic patients.
AB  - In several clinical contexts, the measurement of ATP concentration in T
      lymphocytes has been proposed as a biomarker of immune status, predictive of
      secondary infections. However, the use of such biomarker in lymphopenic patients
      requires some adaptations in the ATP dosage protocol. We used blood from healthy
      volunteers to determine the optimal experimental settings. We investigated
      technical aspects such as the type of anticoagulant for blood sampling, the
      effect of freeze and thaw cycles, the reagent and sample mixing sequence, and the
      optimal dilution buffer. We also shortened the incubation time to 8h, and even
      showed that a 30min incubation may be sufficient. To evaluate the ATP rise upon
      lymphocyte activation, the optimal dose of stimulant was defined to be 4MUg/mL of
      phytohaemagglutinin. Lastly, we determined that the number of T cells needed for
      this measurement was as low as 50,000, which is compatible with the existing
      lymphopenia in clinical settings. This optimized protocol appears ready to be
      assessed in lymphopenic patients to further investigate the interconnection
      between T lymphocyte metabolism and impaired phenotype and functions.

PMID- 27720851
TI  - Vaginal Extrusion of a Ventriculoperitoneal Shunt: A Case Report and Review of
      Literature.
AB  - BACKGROUND: Ventriculoperitoneal shunting is the most common treatment for
      hydrocephalus (excessive cerebrospinal fluid accumulation in the brain), but has
      the potential for serious complications such as shunt migration. Potential
      migration sites include the lateral ventricle mediastinum, gastrointestinal
      tract, abdominal wall, bladder, vagina, and scrotum. CASE: Here, we present a
      rare case of vaginal extrusion of a ventriculoperitoneal shunt. SUMMARY AND
      CONCLUSION: Neurosurgeons and gynecologists should be aware of the potential
      occurrence of this rare complication.

PMID- 27720852
TI  - Intermittent Nitrate Use and Risk of Hip Fracture.
AB  - PURPOSE: Nitrates, commonly used antianginal medications, also have a beneficial
      effect on bone remodeling and bone density, particularly with intermittent use.
      However, their effect on fracture risk is not clear. We examined the relation of
      short-acting nitrate use (proxy for intermittent use) with the risk of hip
      fracture in a large cohort of older adults with ischemic heart disease. METHODS:
      Participants aged 60 years or more with ischemic heart disease and without a
      history of hip fracture from The Health Improvement Network, an electronic
      medical records database in the United Kingdom, were included. The association of
      incident (new) use of short-acting nitrate formulations (nitroglycerin
      sublingual/spray/ointment or isosorbide dinitrate injection/sprays) with incident
      (new-onset) hip fracture risk was examined by plotting Kaplan-Maier curves and
      calculating hazard ratios using Cox proportional hazards regression models.
      Competing risk by death was analyzed in separate analyses. RESULTS: Among 14,451
      pairs of matched nitrate users and nonusers (mean age, 72 +/- 7.6 years, 41%
      women for each cohort), 573 fractures occurred during follow-up (257 nitrate
      users; 316 nonusers). Hip fracture risk was 33% lower among short-acting nitrate
      users compared with nonusers (hazard ratio, 0.67; 95% confidence interval, 0.53
      0.85; P = .0008). Competing risk analysis by death did not change effect
      estimates. CONCLUSIONS: In this large population-based cohort of older adults
      with ischemic heart disease, we found a significant reduction in hip fracture
      risk with the use of short-acting nitrates (intermittent use). Future studies are
      warranted given the potential for nitrates to be potent, inexpensive, and readily
      available antiosteoporotic agents.

PMID- 27720853
TI  - Association Between Gout and Aortic Stenosis.
AB  - BACKGROUND: An independent association between gout and coronary artery disease
      is well established. The relationship between gout and valvular heart disease,
      however, is unclear. The aim of this study was to assess the association between
      gout and aortic stenosis. METHODS: We performed a retrospective case-control
      study. Aortic stenosis cases were identified through a review of outpatient
      transthoracic echocardiography (TTE) reports. Age-matched controls were randomly
      selected from patients who had undergone TTE and did not have aortic stenosis.
      Charts were reviewed to identify diagnoses of gout and the earliest dates of gout
      and aortic stenosis diagnosis. RESULTS: Among 1085 patients who underwent TTE,
      112 aortic stenosis cases were identified. Cases and nonaortic stenosis controls
      (n = 224) were similar in age and cardiovascular comorbidities. A history of gout
      was present in 21.4% (n = 24) of aortic stenosis subjects compared with 12.5% (n
      = 28) of controls (unadjusted odds ratio 1.90, 95% confidence interval 1.05-3.48,
      P = .038). Multivariate analysis retained significance only for gout (adjusted
      odds ratio 2.08, 95% confidence interval 1.00-4.32, P = .049). Among subjects
      with aortic stenosis and gout, gout diagnosis preceded aortic stenosis diagnosis
      by 5.8 +/- 1.6 years. The age at onset of aortic stenosis was similar among
      patients with and without gout (78.7 +/- 1.8 vs 75.8 +/- 1.0 years old, P = .16).
      CONCLUSIONS: Aortic stenosis patients had a markedly higher prevalence of
      precedent gout than age-matched controls. Whether gout is a marker of, or a risk
      factor for, the development of aortic stenosis remains uncertain. Studies
      investigating the potential role of gout in the pathophysiology of aortic
      stenosis are warranted and could have therapeutic implications.

PMID- 27720854
TI  - Neural correlates of judgments of learning - An ERP study on metacognition.
AB  - Metacognitive assessment of performance has been revealed to be one of the most
      powerful predictors of human learning success and academic achievement. Yet,
      little is known about the functional nature of cognitive processes supporting
      judgments of learning (JOLs). The present study investigated the neural
      underpinnings of JOLs, using event-related brain potentials. Participants were
      presented with picture pairs and instructed to learn these pairs. After each
      pair, participants received a task cue, which instructed them to make a JOL (the
      likelihood of remembering the target when only presented with the cue) or to make
      a control judgment. Results revealed that JOLs were accompanied by a positive
      slow wave over medial frontal areas and a bilateral negative slow wave over
      occipital areas between 350ms and 700ms following the task cue. The results are
      discussed with respect to recent accounts on the neural correlates of judgments
      of learning.

PMID- 27720855
TI  - Second-language learning effects on automaticity of speech processing of Japanese
      phonetic contrasts: An MEG study.
AB  - We examined discrimination of a second-language (L2) vowel duration contrast in
      English learners of Japanese (JP) with different amounts of experience using the
      magnetoencephalography mismatch field (MMF) component. Twelve L2 learners were
      tested before and after a second semester of college-level JP; half attended a
      regular rate course and half an accelerated course with more hours per week.
      Results showed no significant change in MMF for either the regular or accelerated
      learning group from beginning to end of the course. We also compared these groups
      against nine L2 learners who had completed four semesters of college-level JP.
      These 4-semester learners did not significantly differ from 2-semester learners,
      in that only a difference in hemisphere activation (interacting with time)
      between the two groups approached significance. These findings suggest that
      targeted training of L2 phonology may be necessary to allow for changes in
      processing of L2 speech contrasts at an early, automatic level.

PMID- 27720856
TI  - Sleep's role in the reconsolidation of declarative memories.
AB  - Sleep is known to support the consolidation of newly encoded and initially labile
      memories. Once consolidated, remote memories can return to a labile state upon
      reactivation and need to become reconsolidated in order to persist. Here we asked
      whether sleep also benefits the reconsolidation of remote memories after their
      reactivation and how reconsolidation during sleep compares to sleep-dependent
      consolidation processes. In three groups, participants were trained on a visuo
      spatial learning task in the presence of a contextual odor. Participants in the
      'reconsolidation' group learned the task on day 1. On day 2, they were subjected
      to a reactivation procedure by presenting the odor cue and a mock recall test in
      the learning context before a 40-min sleep or wake period. Participants in the
      'remote consolidation' group followed the same procedure but did not receive
      reactivation on day 2. Participants in the 'recent consolidation' group skipped
      the procedure on day 1 and learned the task immediately before the sleep or wake
      period. After the sleep or wake interval, memory stability was tested in all
      subjects. The results show that this short 40-min sleep period significantly
      facilitated the reconsolidation of reactivated memories, whereas the
      consolidation of non-reactivated remote memories was less affected and recently
      encoded memories did not benefit at all. These findings tentatively suggest that
      sleep has a beneficial effect on the reconsolidation of remote memories, acting
      at a faster rate than sleep-associated consolidation.

PMID- 27720858
TI  - Ocular parasitoses: A comprehensive review.
AB  - Parasitic infections of the eyes are a major cause of ocular diseases across the
      globe. The causative agents range from simple organisms such as unicellular
      protozoans to complex metazoan helminths. The disease spectrum varies depending
      on the geographic location, prevailing hygiene, living and eating habits of the
      inhabitants, and the type of animals that surround them. They cause enormous
      ocular morbidity and mortality not because they are untreatable, but largely due
      to late or misdiagnosis, often from unfamiliarity with the diseases produced. We
      provide an up-to-date comprehensive overview of the ophthalmic parasitoses. Each
      section describes the causative agent, mode of transmission, geographic
      distribution, ocular pathologies, and their management for common parasites with
      brief mention of the ones that are rare.

PMID- 27720857
TI  - Low protein to carbohydrate ratio diet delays onset of Parkinsonism like
      phenotype in Drosophila melanogaster parkin null mutants.
AB  - Dietary management plays a key role in the treatment of many diseases. However,
      no prospective studies have critically investigated the potential for dietary
      modification to delay the onset, or slow the progression, of Parkinson's Disease
      (PD). To study whether manipulating the Protein to Carbohydrate (P:C) ratio in
      the diet could affect the progression of PD, we compared Drosophila melanogaster
      parkin null mutants and their experimental controls fed with diets differing in
      their P:C ratio. We considered lifespan and feeding behaviors as well as motor
      and cellular functions on the 1:2 and 1:16 P:C diets. We observe that parkin
      mutants have a longer lifespan when fed the 1:16 P:C compared to those fed the
      1:2 P:C diet. Parkin mutants fed the 1:16 P:C diet have delayed climbing deficit,
      increased resistance to starvation. Mutant flies fed the 1:16 P:C diet also have
      improved mitochondrial functions as evidenced by increased respiratory control
      ratio and mitochondrial membrane potential and decreased reactive oxygen species
      production and superoxide activity especially in old parkin mutants. Combined,
      these results suggest that dietary management has potential to delay the
      progression of PD.

PMID- 27720859
TI  - Involvement of P2X7 receptors in retinal ganglion cell apoptosis induced by
      activated Muller cells.
AB  - Muller cell reactivation (gliosis) is an early response in glaucomatous retina.
      Previous studies have demonstrated that activation of P2X7 receptors results in
      retinal ganglion cell (RGC) apoptosis. Here, the issues of whether and how
      activated Muller cells may contribute to RGC apoptosis through P2X7 receptors
      were investigated. Either intravitreal injection of (S)-3,5
      dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR
      I) agonist, in normal rat retinas, or DHPG treatment of purified cultured rat
      retinal Muller cells induced an increase in glial fibrillary acidic protein
      (GFAP) expression, indicative of Muller cell gliosis. In addition, an increase in
      adenosine triphosphate (ATP) release from purified cultured Muller cells was
      detected during DHPG treatment (for 10 min to 48 h), which was mediated by the
      intracellular mGluR5/Gq/PI-PLC/PKC signaling pathway. Intravitreal injection of
      DHPG mimicked the reduction in the number of fluorogold retrogradely labeled RGCs
      in chronic ocular hypertension (COH) rats. Treatment with the conditioned culture
      medium (CM) obtained from the DHPG-activated Muller cell medium induced an
      increase in the number of TUNEL-positive cells in cultured RGCs, which was
      mimicked by benzoylbenzoyl adenosine triphosphate (BzATP), a P2X7 receptor
      agonist, but was partially blocked by brilliant blue G (BBG), a P2X7 receptor
      antagonist. Moreover, the CM treatment of cultured RGCs significantly increased
      Bax protein level and decreased Bcl-2 protein level, which was also mimicked by
      BzATP and partially blocked by BBG, respectively. These results suggest that
      reactivated Muller cells may release excessive ATP, in turn leading to RGC
      apoptosis through activating P2X7 receptors in these cells.

PMID- 27720861
TI  - A Burkholderia sacchari cell factory: production of poly-3-hydroxybutyrate,
      xylitol and xylonic acid from xylose-rich sugar mixtures.
AB  - Efficient production of poly-3-hydroxybutyrate (P(3HB)) based on glucose-xylose
      mixtures simulating different types of lignocellulosic hydrolysate (LCH) was
      addressed using Burkholderia sacchari, a wild strain capable of metabolizing both
      sugars and producing P(3HB). Carbon catabolite repression was avoided by
      maintaining glucose concentration below 10g/L. Xylose concentrations above 30g/L
      were inhibitory for growth and production. In fed-batch cultivations, pulse size
      and feed addition rate were controlled in order to reach high productivities and
      efficient sugar consumptions. High xylose uptake and P(3HB) productivity were
      attained with glucose-rich mixtures (glucose/xylose ratio in the feed=1.5w/w)
      using high feeding rates, while with xylose-richer feeds (glucose/xylose=0.8w/w),
      a lower feeding rate is a robust strategy to avoid xylose build-up in the medium.
      Xylitol production was observed with xylose concentrations in the medium above 30
      40g/L. With sugar mixtures featuring even lower glucose/xylose ratios, i.e.
      xylose-richer feeds (glucose/xylose=0.5), xylonic acid (a second byproduct) was
      produced. This is the first report of the ability of Burkholderia sacchari to
      produce both xylitol and xylonic acid.

PMID- 27720860
TI  - The adult zebrafish retina: In vivo optical sectioning with Confocal Scanning
      Laser Ophthalmoscopy and Spectral-Domain Optical Coherence Tomography.
AB  - Non-invasive imaging is an invaluable diagnostic tool in ophthalmology. Two
      imaging devices, the scanning laser ophthalmoscope (SLO) and spectral domain
      optical coherence tomography (SDOCT), emerged from the clinical realm to provide
      research scientists with a real-time view of ocular morphology in living animals.
      We utilized these two independent imaging modalities in a complementary manner to
      perform in vivo optical sectioning of the adult zebrafish retina. Due to the very
      high optical power of the zebrafish lens, the confocal depth of field is narrow,
      allowing for detailed en face views of specific retinal layers, including the
      cone mosaic. Moreover, we demonstrate that both native reflectance, as well as
      fluorescent features observed by SLO, can be combined with axial in-depth
      information obtained by SDOCT. These imaging approaches can be used to screen for
      ocular phenotypes and monitor retinal pathology in a non-invasive manner.

PMID- 27720862
TI  - Urinary incontinence in nulliparous women aged 25-64 years: a national survey.
AB  - BACKGROUND: A systematic survey of pelvic floor disorders in nulliparous women
      has not been presented previously. OBJECTIVE: The purpose of this study was to
      determine the prevalence of urinary incontinence parameters in a large cohort of
      nonpregnant, nulliparous women, and thereby construct a reference group for
      comparisons with parous women. STUDY DESIGN: This postal and World Wide Web-based
      questionnaire survey was conducted in 2014. The study population was identified
      from the Total Population Register in Sweden and comprised women who had not
      given birth and were aged 25-64 years. Four independent age-stratified, random
      samples comprising 20,000 women were obtained from the total number of eligible
      nullipara (n = 625,810). A 40-item questionnaire about pelvic floor symptoms, its
      severity, and its consequences were used. Age-dependent differences for various
      aspects of urinary incontinence were analyzed with the youngest group (25-34
      years) serving as reference. Crude and body mass index-adjusted prevalence and
      its 95% confidence limits were calculated for each 10-year category. RESULTS: The
      response rate was 52% and the number of study participants was 9197. Urinary
      incontinence increased >5-fold from 9.7% in the youngest women with a body mass
      index <25 kg/m2 to 48.4% among the oldest women with a body mass index >=35
      kg/m2. The prevalence of bothersome urinary incontinence almost tripled from 2.8
      7.9% among all nulliparas. The proportion with bothersome urinary incontinence
      among incontinent women increased from 24.4% in the youngest age group to 32.3%
      in the age group 55-64 years. Nocturia >=2/night increased 4-fold to 17.0% and
      leakage >=1/wk increased 3-fold to 12.8% among the oldest women. Mixed urinary
      incontinence increased from 22.9-40.9% among the oldest 0-para with incontinence,
      whereas stress urinary incontinence decreased inversely from 43.6-33.0%. In the
      total cohort surgical treatment for urinary incontinence occurred in 3 per
      thousand. CONCLUSION: Almost every aspect of urinary incontinence was present in
      nulliparous women of all ages and prevalence increased with advancing age between
      25-64 years. This must be taken into account when using nullipara as a control
      group in comparisons with parous women to estimate the effect of pregnancy and
      childbirth.

PMID- 27720863
TI  - Parity, weight change, and maternal risk of cardiovascular events.
AB  - BACKGROUND: High parity has been suggested to increase risk of maternal
      cardiovascular disease independent of body mass index measured after
      childbearing. Pregnancy is, however, associated with persistent weight gain and
      metabolic changes that, independent of parity, increase the risk of
      cardiovascular disease. It could therefore be questioned if high parity
      independently increases the risk of cardiovascular disease or if this association
      may be confounded, mediated, or modified by other parity-related factors.
      OBJECTIVE: We sought to investigate the association between parity and risk of
      cardiovascular disease, and secondary outcomes in terms of myocardial infarction
      and cerebral infarction, with particular focus on potential mediation by
      anthropometric measures and effect modification by lactation. STUDY DESIGN: We
      used data from 16,515 female participants (age 44.5-73.6 years) of the population
      based Malmo Diet and Cancer Study with baseline examination from 1991 through
      1996. The Malmo Diet and Cancer Study was followed up throughout 2010, with a
      median follow-up of 15.8 years. We used Cox proportional hazards model to examine
      the association between parity and cardiovascular disease. RESULTS: Adjusted for
      age and other potential confounders, grand multiparous women (>=5 children) had
      an increased risk of cardiovascular disease (hazard ratio, 1.60; 95% confidence
      interval, 1.20-2.14), myocardial infarction (hazard ratio, 1.68; 95% confidence
      interval, 1.15-2.45), and cerebral infarction (hazard ratio, 1.74; 95% confidence
      interval, 1.18-2.58) compared to women with 2 children. Additional adjustment for
      baseline body mass index and weight change since age 20 years attenuated the
      risk, but the increased risk for cardiovascular disease (hazard ratio, 1.38; 95%
      confidence interval, 1.02-1.87) and myocardial infarction (hazard ratio, 1.53;
      95% confidence interval, 1.04-2.26) in grand multiparous women remained
      significant. Models stratified by lactation time showed that risk was only raised
      in grand multiparous women who had a mean lactation time of <4 mo/child. In
      sensitivity analyses excluding women with a history of diabetes at baseline, risk
      estimates for grand multiparous women became nonsignificant in the full model.
      CONCLUSION: Part of the increased risk of cardiovascular disease and myocardial
      infarction in grand multiparous women seems to be mediated by weight gain and
      potentially by higher likelihood of type 2 diabetes mellitus. Lactation may
      modify the increased risk of grand multiparity in that longer duration might
      offset the cardiovascular disease risk.

PMID- 27720864
TI  - Application of cement on strategic vertebrae in the treatment of the osteoporotic
      spine.
AB  - BACKGROUND CONTEXT: The application of pedicle screws with cement to strengthen
      the fixation of the osteoporotic spine has increasingly gained popularity.
      However, the technique has also led to an increase in cement-related
      complications. PURPOSE: The aim of the present study was to compare the clinical
      and radiological results of the patients with degenerative spinal pathologies who
      were treated with pedicle screws and cement injections on all segments versus
      those who were treated with cement injections only on the strategic vertebrae
      selected. STUDY DESIGN: A retrospective clinical study. PATIENT SAMPLE: The
      sample consists of 31 patients who underwent spinal surgery due to degenerative
      spinal pathologies. OUTCOME MEASURES: Patients were assessed for the adequate
      spinal fusion and cement-related complication parameters. METHODS: Thirty-one
      patients with a minimum follow-up period of 2 years were divided into two groups
      and evaluated. Group A consisted of 17 patients (14 females, 3 males; mean age:
      68.1 years) with cemented pedicle screws and Group B consisted of 14 patients (12
      females, 2 males; mean age: 67.2 years) with cemented screws on selected
      vertebrae alone. Selection of the strategic vertebrae was made by taking the most
      stressed regions in the fusion site into account. Prophylactic vertebroplasty was
      performed in all patients in Group A and on strategic segments in Group B to
      avoid an adjacent segment fracture. Early- and late-term complications during the
      follow-up period were recorded. RESULTS: Mean follow-up period was 51.8 (range:
      31 to 80) months in Group A and 41.2 (range: 26 to 61) months in Group B.
      Cemented pedicle screws were bilaterally placed on 94 vertebrae in Group A. In
      Group B, cement was applied on 28 of 80 vertebrae. Including the prophylactic
      vertebroplasties, a total of 111 cement applications were performed in Group A
      and 38 in Group B. Cement embolism, symptomatic chest discomfort, and duration of
      surgery were significantly higher in Group A (p<.05). No adjacent segment
      fracture in the proximal or distal vertebra, implant failure, or loss of
      correction was seen throughout the follow-up period. CONCLUSIONS: The application
      of cemented pedicle screws on all segments of the osteoporotic spine increases
      the cement volume and rate of cement-related complications. Cementing the
      strategic vertebrae alone will enhance the fixation strength and endurance and
      decrease the complications caused by cement application.

PMID- 27720865
TI  - Cytomegalovirus reactivation enhances the virulence of Staphylococcus aureus
      pneumonia in a mouse model.
AB  - OBJECTIVES: Cytomegalovirus (CMV) reactivation in intensive care unit patients
      may increase mortality and favour bacterial pneumonia. We developed a murine
      model to compare the severity of staphylococcal pneumonia after CMV reactivation
      and in CMV-negative mice. METHODS: Balb/c mice were primo-infected with murine
      cytomegalovirus (MCMV n=90) or received saline (control n=90). After latency, all
      mice underwent caecal ligation and puncture to trigger MCMV reactivation in MCMV
      primary-infected mice. Surviving animals received an intra-nasal inoculation with
      methicillin-susceptible Staphylococcus aureus (MSSA) to induce pneumonia.
      Mortality, lung bacterial count, histology and interferon-alpha and gamma serum
      levels were compared in MCMV reactivated and control mice 2, 5 and 15 days after
      pneumonia. RESULTS: After MSSA pneumonia, MCMV mice showed a trend towards a
      higher mortality (9.4% versus 0%; p 0.09) and a higher weight loss (2.2 (0.6-4.1
      g) versus 0.7 (-0.3 to 1.3 g); p 0.005). The lung bacterial count was higher in
      MCMV mice 2 days (5*103 (103 to 3*105) versus 102 (0 to 4*102) CFU/lung; p 0.007)
      and 5 days (2.5*104 (1.6*104 to 6.5*105) versus 15 (10-40) CFU/lung; p 0.005)
      after MSSA pneumonia. 8/40 (20%) MCMV mice developed lung abscesses compared to
      0% in control (p 0.011). Interferon-alpha serum levels 2 days after
      staphylococcal pneumonia were higher in MCMV mice. CONCLUSIONS: MCMV reactivation
      decreased lung bacterial clearance and favoured the development of staphylococcal
      abscessing pneumonia. CMV reactivation may be responsible for a higher
      susceptibility to bacterial sepsis.

PMID- 27720866
TI  - Morphological changes induced by beta-lactam antibiotics observed on Gram
      staining.

PMID- 27720867
TI  - The role of test-retest reliability in measuring individual and group differences
      in executive functioning.
AB  - BACKGROUND: Studies testing for individual or group differences in executive
      functioning can be compromised by unknown test-retest reliability. NEW METHOD:
      Test-retest reliabilities across an interval of about one week were obtained from
      performance in the antisaccade, flanker, Simon, and color-shape switching tasks.
      There is a general trade-off between the greater reliability of single mean RT
      measures, and the greater process purity of measures based on contrasts between
      mean RTs in two conditions. The individual differences in RT model recently
      developed by Miller and Ulrich was used to evaluate the trade-off. RESULTS: Test
      retest reliability was statistically significant for 11 of the 12 measures, but
      was of moderate size, at best, for the difference scores. The test-retest
      reliabilities for the Simon and flanker interference scores were lower than those
      for switching costs. COMPARISON WITH EXISTING METHODS: Standard practice
      evaluates the reliability of executive-functioning measures using split-half
      methods based on data obtained in a single day. Our test-retest measures of
      reliability are lower, especially for difference scores. These reliability
      measures must also take into account possible day effects that classical test
      theory assumes do not occur. CONCLUSIONS: Measures based on single mean RTs tend
      to have acceptable levels of reliability and convergent validity, but are
      "impure" measures of specific executive functions. The individual differences in
      RT model shows that the impurity problem is worse than typically assumed.
      However, the "purer" measures based on difference scores have low convergent
      validity that is partly caused by deficiencies in test-retest reliability.

PMID- 27720868
TI  - The use of the Emotional-Object Recognition as an assay to assess learning and
      memory associated to an aversive stimulus in rodents.
AB  - BACKGROUND: Emotionally salient experiences induce the formation of explicit
      memory traces, besides eliciting automatic or implicit emotional memory in
      rodents. This study aims at investigating the implementation of a novel task for
      studying the formation of limbic memory engrams as a result of the acquisition-
      and retrieval- of fear-conditioning - biased declarative memory traces, measured
      by animal discrimination of an "emotional-object". Moreover, by using this new
      method we investigated the potential interactions between stimulation of
      cannabinoid transmission and integration of emotional information and cognitive
      functioning. NEW METHOD: The Emotional-Object Recognition task is composed of 3
      following sessions: habituation; cued fear-conditioned learning; emotional
      recognition. Rats are exposed to Context "B chamber" for habituation and cued
      fear-conditioning, and tested in Context "A chamber" for emotional-object
      recognition. RESULTS: Cued fear-conditioning induces a reduction in emotional
      object exploration time during the Emotional-Object Recognition task in controls.
      The activation of cannabinoid signalling impairs limbic memory formation, with
      respect to vehicle. COMPARISON TO EXISTING METHODS: The Emotional-Object
      Recognition test overcomes several limitations of commonly employed methods that
      explore declarative-, spatial memory and fear-conditioning in a non-integrated
      manner. It allows the assessment of unbiased cognitive indicators of emotional
      learning and memory. CONCLUSIONS: The Emotional-Object Recognition task is a
      valuable tool for investigating whether, and at what extent, specific drugs or
      pathological conditions that interfere with the individual affective/emotional
      homeostasis, can modulate the formation of emotionally salient explicit memory
      traces, thus jeopardizing control and regulation of animal behavioural strategy.

PMID- 27720869
TI  - Caffeic acid attenuated acetaminophen-induced hepatotoxicity by inhibiting ERK1/2
      mediated early growth response-1 transcriptional activation.
AB  - Caffeic acid (CA) is a natural compound abundant in fruits, coffee and plants.
      This study aims to investigate the involved mechanism of the therapeutic
      detoxification of CA against acetaminophen (APAP)-induced hepatotoxicity. CA (10,
      30 mg/kg) was orally given to mice at 1 h after mice were pre-administrated with
      APAP (300 mg/kg). The therapeutic detoxification of CA against APAP-induced
      hepatotoxicity was observed by detecting serum aminotransferases, liver
      malondialdehyde (MDA) amount and liver histological evaluation in vivo. CA
      reduced APAP-induced increase in the mRNA expression of early growth response 1
      (Egr1) in hepatocytes, and inhibited APAP-induced Egr1 transcriptional activation
      in vitro and in vivo. CA reduced the increased expression of growth arrest and
      DNA-damage-inducible protein (Gadd45)alpha induced by APAP in hepatocytes.
      Moreover, Egr1 siRNA reduced Gadd45alpha expression and reversed APAP-induced
      cytotoxicity in hepatocytes. Further results showed that CA blocked APAP-induced
      activation of extracellular-regulated protein kinase (ERK1/2) signaling cascade
      in vivo and in vitro. In addition, the application of ERK1/2 inhibitors (PD98059
      and U0126) abrogated the nuclear translocation of Egr1 induced by APAP in
      hepatocytes. In conclusion, this study demonstrated the therapeutic
      detoxification of CA against APAP-induced liver injury, and the inhibition of CA
      on ERK1/2-mediated Egr1 transcriptional activation was involved in this process.

PMID- 27720870
TI  - Achieving resistance specificity in prostate cancer.
AB  - Prostate (CaP) cancer is the second-leading cause of cancer-related mortality in
      men in Western societies. Androgen receptor (AR) signaling is a critical survival
      pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains
      the principal treatment for patients with locally advanced and metastatic
      disease. Although a majority of patients initially respond to ADT, most will
      eventually develop castrate resistance. The recent discovery that AR signaling
      persists during systemic castration via intratumoral production of androgens led
      to the development of novel anti-androgen therapies. Although these therapies
      effectively palliate symptoms and prolong life, metastatic castration-resistant
      prostate cancer remains incurable. Recent studies suggest that epithelial
      plasticity, which covers a range of changes in differentiation and cell behavior,
      with full epithelial integrity at one end and epithelial-mesenchymal Transition
      (EMT) as the full realization of a plasticity is regulated by microRNAs (miRNAs).
      MicroRNAs are involved in human tumourigenesis and are aberrantly expressed in
      CaP cell lines, xenografts and clinical tissues and is associated with enhanced
      survival signaling, proliferation, migration, invasion, integrin-mediated
      adhesion, EMT, and drug resistance. Due to the oncogenic or tumor suppressive
      properties of CaP-related miRNAs, they are likely to be of clinical use as
      therapeutic targets for prostate cancer treatment in the near future. This review
      summarizes our current understanding of CaP and castration-recurrent CaP (CR-CaP)
      to earlier studies that characterized ADT and the molecular mechanisms that
      facilitate the transition from androgen-stimulated CaP to CR-CaP.

PMID- 27720871
TI  - Tunable doxorubicin release from polymer-gated multiwalled carbon nanotubes.
AB  - Two pH and temperature controlled drug delivery systems for cancer therapy are
      here reported by using vapour phase and liquid phase functionalized multiwalled
      carbon nanotubes (MWCNT). Both oxidized MWCNT were functionalized at the carboxyl
      groups with a short hydrophilic polyethylene glycol (PEG) chain. The nanosystems
      were loaded with doxorubicin and covered with the biocompatible polymer
      polylactide, able to form hydrogen bonding with PEG and to entrape the drug
      inside the two polymeric chains. The different oxidative reaction conditions of
      MWCNT have demonstrated to deeply affect their agglomeration ability and the
      available reactive surface area for drug loading which in turn, affected the drug
      release abilities of the synthesized polymer-gated drug delivery systems. The in
      vitro release abilities as well as their antiproliferative effect on three
      different human cancer cell lines were evaluated and compared, highlighting the
      possibility to tune the amount of drug released by controlling the
      functionalization degree of the carbon nanotube based material. Biological tests
      highlighted the high biocompatibility of both systems and their ability to
      deliver doxorubicin to cancer cells.

PMID- 27720873
TI  - Mechanisms of cellular uptake and endosomal escape of calcium-siRNA
      nanocomplexes.
AB  - Ca2+-siRNA nanocomplexes represent a simple yet an effective platform for siRNA
      delivery into the cell cytoplasm, with subsequent successful siRNA-induced target
      gene silencing. Herein, we aimed to elucidate the roles played by calcium ions in
      siRNA nanocomplex formation, cell uptake, and endosomal escape. We investigated
      whether the replacement of Ca2+in the nanocomplex by other bivalent cations would
      affect their cell entry and subsequent gene silencing. Our results indicate that
      Mg2+ and Ba2+ lead to the formation of nanocomplexes of similar physical features
      (size=100nm, surface charge zeta=-8mV) as the Ca2+-siRNA nanocomplexes. Yet,
      these nanocomplexes were not uptaken by the cells to the same extent as those
      prepared with Ca2+, and siRNA-induced target gene silencing was not obtained.
      Cell internalization of Ca2+--siRNA nanocomplexes, examined by employing chemical
      inhibitors to clathrin-, caveolin- and dynamin-mediated endocytosis pathways,
      indicated the involvement of all mechanisms in the process. Inhibition of
      endosome acidification by bafilomycin completely abolished the siRNA-mediated
      silencing by Ca2+-siRNA nanocomplexes. Collectively, our results indicate that
      Ca2+ promotes cell internalization and rapid endosomal escape, thus leading to
      the efficient siRNA-induced target gene silencing elicited by the Ca2+-siRNA
      nanocomplexes.

PMID- 27720872
TI  - LARETH-25 and beta-CD improve central transitivity and central pharmacological
      effect of the GLP-2 peptide.
AB  - Depression is a common mental disorder. More than 350 million people of all ages
      suffer from depression worldwide. Although a number of antidepressants are
      available, >20% of patients with major depressive disorder suffer from treatment
      resistant depression. Therefore, development of novel therapeutics to overcome
      this condition is required. We reported that intracerebroventricular
      administration of glucagon-like peptide-2 (GLP-2) exerts antidepressant-like
      effects treated with or without adrenocorticotropic hormone. In the present
      study, we developed a nasal formulation of GLP-2 containing 5% polyoxyethylene
      (25) lauryl ether and 1% beta-cyclodextrin that enhanced the resistance of GLP-2
      to inactivation by dipeptidyl peptidase-4. Intranasal administration of this
      formulation (60MUg/kg) increased the delivery of GLP-2 to the brain and had
      antidepressant-like effects on rats. These results suggest the potential of the
      GLP-2 nasal formulation for use as a novel antidepressant.

PMID- 27720875
TI  - The effect of structurally related impurities on crystallinity reduction of
      sulfamethazine by grinding.
AB  - In this study, the effect of structurally related impurities on crystallinity
      reduction of sulfamethazine by grinding was evaluated. The crystallinity of
      sulfamethazine was not decreased when it was ground alone. However, when
      structurally related impurities with sulfonamide derivatives were blended, the
      crystallinity of sulfamethazine was decreased by grinding. Other materials
      without a sulfonamide moiety showed no such effect. The Raman spectra of
      sulfamethazine demonstrated that there was a difference between its crystalline
      and amorphous states within its sulfonamide structure. It was suggested that the
      sulfonamide structure of the impurities was important in causing the inhibition
      of recrystallization of sulfamethazine during grinding.

PMID- 27720874
TI  - Continuous production of itraconazole-based solid dispersions by hot melt
      extrusion: Preformulation, optimization and design space determination.
AB  - The purpose of this work was to increase the solubility and the dissolution rate
      of itraconazole, which was chosen as the model drug, by obtaining an amorphous
      solid dispersion by hot melt extrusion. Therefore, an initial preformulation
      study was conducted using differential scanning calorimetry, thermogravimetric
      analysis and Hansen's solubility parameters in order to find polymers which would
      have the ability to form amorphous solid dispersions with itraconazole.
      Afterwards, the four polymers namely Kollidon(r) VA64, Kollidon(r) 12PF,
      Affinisol(r) HPMC and Soluplus(r), that met the set criteria were used in hot
      melt extrusion along with 25wt.% of itraconazole. Differential scanning confirmed
      that all four polymers were able to amorphize itraconazole. A stability study was
      then conducted in order to see which polymer would keep itraconazole amorphous as
      long as possible. Soluplus(r) was chosen and, the formulation was fine-tuned by
      adding some excipients (AcDiSol(r), sodium bicarbonate and poloxamer) during the
      hot melt extrusion process in order to increase the release rate of itraconazole.
      In parallel, the range limits of the hot melt extrusion process parameters were
      determined. A design of experiment was performed within the previously defined
      ranges in order to optimize simultaneously the formulation and the process
      parameters. The optimal formulation was the one containing 2.5wt.% of AcDiSol(r)
      produced at 155 degrees C and 100rpm. When tested with a biphasic dissolution
      test, more than 80% of itraconazole was released in the organic phase after 8h.
      Moreover, this formulation showed the desired thermoformability value. From these
      results, the design space around the optimum was determined. It corresponds to
      the limits within which the process would give the optimized product. It was
      observed that a temperature between 155 and 170 degrees C allowed a high
      flexibility on the screw speed, from about 75 to 130rpm.

PMID- 27720876
TI  - ATR-FTIR spectroscopic imaging to study the drying and dissolution of
      pharmaceutical polymer-based films.
AB  - Pharmaceutical film dosage forms have recently become of interest to
      pharmaceutical formulation development, particularly for patients who experience
      difficulty in swallowing tablets or capsules. Furthermore, formulation scientists
      require a reliable analytical approach to reveal vital insight and investigate
      the drying process of these films to consolidate suitable quality control. Since
      most of the polymer-based films containing a drug are produced via solution or
      dispersion states, an estimation of the physicochemical properties of drugs
      during drying and dissolution is critical to design novel formulations with the
      consideration to control drug release, i.e. safety and efficacy to patients. This
      work presents the novel application of attenuated total reflection-Fourier
      transform infrared (ATR-FTIR) spectroscopic imaging to study the drying process
      and dissolution behaviour of polymer-based films. Two types of the ibuprofen
      containing films, hydroxypropyl methylcellusose (HPMC) based films for immediate
      release and polyvinylpyrrolidone (PVP) based films for extended release, were
      studied in modified pH environments and changing hydrophobicity. ATR-FTIR imaging
      has revealed important information on water ingress into the films and the
      presence, distribution, and physicochemical state of the drug. ATR-FTIR imaging
      is a powerful technique to investigate and to deeply understand physicochemical
      processes for pharmaceutical polymer-based films.

PMID- 27720877
TI  - Near-infrared chemical imaging (NIR-CI) of 3D printed pharmaceuticals.
AB  - Hot-melt extrusion and 3D printing are enabling manufacturing approaches for
      patient-centred medicinal products. Hot-melt extrusion is a flexible and
      continuously operating technique which is a crucial part of a typical processing
      cycle of printed medicines. In this work we use hot-melt extrusion for
      manufacturing of medicinal films containing indomethacin (IND) and
      polycaprolactone (PCL), extruded strands with nitrofurantoin monohydrate (NFMH)
      and poly (ethylene oxide) (PEO), and feedstocks for 3D printed dosage forms with
      nitrofurantoin anhydrate (NFAH), hydroxyapatite (HA) and poly (lactic acid)
      (PLA). These feedstocks were printed into a prototype solid dosage form using a
      desktop 3D printer. These model formulations were characterized using near
      infrared chemical imaging (NIR-CI) and, more specifically, the image analytical
      data were analysed using multivariate curve resolution-alternating least squares
      (MCR-ALS). The MCR-ALS algorithm predicted the spatial distribution of IND and
      PCL in the films with reasonable accuracy. In the extruded strands both the
      chemical mapping of the components in the formulation as well as the solid form
      of the active compound could be visualized. Based on the image information the
      total nitrofurantoin and PEO contents could be estimated., The dehydration of
      NFMH to NFAH, a process-induced solid form change, could be visualized as well.
      It was observed that the level of dehydration increased with increasing
      processing time (recirculation during the mixing phase of molten PEO and
      nitrofurantoin). Similar results were achieved in the 3D printed solid dosage
      forms produced from the extruded feedstocks. The results presented in this work
      clearly demonstrate that NIR-CI in combination with MCR-ALS can be used for
      chemical mapping of both active compound and excipients, as well as for
      visualization of solid form variation in the final product. The suggested NIR-CI
      approach is a promising process control tool for characterization of innovative
      patient-centred medicinal products.

PMID- 27720878
TI  - Theoretical modeling of actin-retrograde-flow passing clusters of confined T cell
      receptors.
AB  - Through the activation process of T cells, actin filaments move from the cell
      periphery toward the cell center. The moving filaments engage with T cell
      receptors and thus contribute to transportation of the signaling molecules. To
      study the connection between the moving actin filaments and T cell receptors, an
      experiment available in the literature has measured filaments flow velocity
      passing over a region of confined clusters of receptors. It shows that flow
      velocity decreases in the proximity of the receptors, and then regains its normal
      value after traversing the region, suggesting a dissipative friction-like
      connection. In this work, we develop a minimal theoretical model to re-examine
      this experiment. The model brings the insight that, in contrast to the first
      impression that the experiment gives, the direct necessity of having a minimum in
      the velocity profile is not the locally high friction region, but a combined
      driving force of push from upstream and pull from within and downstream of the
      system. The predicted driving force integrates our current understanding of the
      spatially dependent role of the myosin motor proteins and the actin
      polymerization-machinery, which make the pulling and pushing forces,
      respectively.

PMID- 27720879
TI  - Detrended cross-correlation coefficient: Application to predict apoptosis protein
      subcellular localization.
AB  - Apoptosis, or programed cell death, plays a central role in the development and
      homeostasis of an organism. Obtaining information on subcellular location of
      apoptosis proteins is very helpful for understanding the apoptosis mechanism. The
      prediction of subcellular localization of an apoptosis protein is still a
      challenging task, and existing methods mainly based on protein primary sequences.
      In this paper, we introduce a new position-specific scoring matrix (PSSM)-based
      method by using detrended cross-correlation (DCCA) coefficient of non-overlapping
      windows. Then a 190-dimensional (190D) feature vector is constructed on two
      widely used datasets: CL317 and ZD98, and support vector machine is adopted as
      classifier. To evaluate the proposed method, objective and rigorous jackknife
      cross-validation tests are performed on the two datasets. The results show that
      our approach offers a novel and reliable PSSM-based tool for prediction of
      apoptosis protein subcellular localization.

PMID- 27720880
TI  - Kinetics of the formation of a protein corona around nanoparticles.
AB  - Interaction of metal or oxide nanoparticles (NPs) with biological soft matter is
      one of the central phenomena in basic and applied biology-oriented nanoscience.
      Often, this interaction includes adsorption of suspended proteins on the NP
      surface, resulting in the formation of the protein corona around NPs.
      Structurally, the corona contains a "hard" monolayer shell directly contacting a
      NP and a more distant weakly associated "soft" shell. Chemically, the corona is
      typically composed of a mixture of distinct proteins. The corresponding
      experimental and theoretical studies have already clarified many aspects of the
      corona formation. The process is, however, complex, and its understanding is
      still incomplete. Herein, we present a kinetic mean-field model of the formation
      of the "hard" corona with emphasis on the role of (i) protein-diffusion
      limitations and (ii) interplay between competitive adsorption of distinct
      proteins and irreversible reconfiguration of their native structure. The former
      factor is demonstrated to be significant only in the very beginning of the corona
      formation. The latter factor is predicted to be more important. It may determine
      the composition of the corona on the time scales comparable or longer than a few
      hours.

PMID- 27720881
TI  - Bronchiectasis Severity Is an Independent Risk Factor for Vascular Disease in a
      Bronchiectasis Cohort.
AB  - BACKGROUND: Interest in the association of vascular disease with COPD and
      pneumonia has increased, but there is a lack of research in this area with
      patients with bronchiectasis. METHODS: A retrospective study of 400 patients
      attending a specialist bronchiectasis clinic in NHS Lothian (Edinburgh, UK)
      between May 2013 and September 2014 was conducted. The study assessed the
      prevalence of vascular disease (ischemic heart disease, cerebrovascular disease,
      peripheral vascular disease, and atrial fibrillation). Using multivariable
      models, independent risk factors were identified for vascular disease that
      developed following the diagnosis of bronchiectasis. RESULTS: The study included
      400 patients. There was preexisting vascular disease (ie, before the diagnosis of
      bronchiectasis) in 44 patients (11%), and vascular disease occurred after the
      diagnosis of bronchiectasis after a mean of 9.4 years (95% CI, 6.0-12.8 years) in
      45 patients (11%). Independent factors associated with all-cause vascular disease
      after the diagnosis of bronchiectasis included male sex, hypertension, receiving
      long-term statin therapy, and having moderate-severity bronchiectasis or worse.
      CONCLUSIONS: In conclusion, bronchiectasis severity is independently associated
      with the development of vascular disease after the diagnosis of bronchiectasis.
      Future studies addressing the impact of primary and secondary prevention are
      warranted.

PMID- 27720884
TI  - Histopathological subgroups in knee osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We
      hypothesised that different histopathological features characterise different
      stages during knee OA progression, and that discrete subgroups can be defined
      based on validated measures of OA histopathological features. DESIGN: Medial
      tibial plateaux and synovium were from 343 post-mortem (PM) and 143 OA
      arthroplasty donations. A 'chondropathy/osteophyte' group (n = 217) was
      classified as PM cases with osteophytes or macroscopic medial tibiofemoral
      chondropathy lesions >=grade 3 to represent pre-surgical (early) OA. 'Non
      arthritic' controls (n = 48) were identified from the remaining PM cases. Mankin
      histopathological scores were subjected to Rasch analysis and supplemented with
      histopathological scores for subchondral bone marrow replacement and synovitis.
      Item weightings were derived by principle components analysis (PCA).
      Histopathological subgroups were sought using latent class analysis (LCA).
      RESULTS: Chondropathy, synovitis and osteochondral pathology were each associated
      with OA at arthroplasty, but each was also identified in some 'non-arthritic'
      controls. Tidemark breaching in the chondropathy/osteophyte group was greater
      than in non-arthritic controls. Three histopathological subgroups were
      identified, characterised as 'mild OA', or 'severe OA' with mild or
      moderate/severe synovitis. CONCLUSIONS: Presence and severity of synovitis helps
      define distinct histopathological OA subgroups. The absence of a discrete
      'normal' subgroup indicates a pathological continuum between normality and OA
      status. Identifying specific pathological processes and their clinical correlates
      in OA subgroups has potential to accelerate the development of more effective
      therapies.

PMID- 27720882
TI  - Association Between Insomnia and Asthma Burden in the Severe Asthma Research
      Program (SARP) III.
AB  - BACKGROUND: Sleep difficulties are commonly reported by patients with asthma;
      however, the prevalence of insomnia and its association with disease burden and
      well-being is unknown. We aimed to determine the prevalence of insomnia, defined
      as combined sleep-specific complaints with associated daytime symptoms, among a
      large sample of adults with asthma, and to compare well-being, asthma control,
      and asthma-related health care utilization in individuals with asthma and
      insomnia and those without insomnia. METHODS: Baseline data from adults with
      physician-confirmed asthma enrolled in the Severe Asthma Research Program III was
      used for analyses (N = 714). Participants completed the Insomnia Severity Index
      (ISI), Asthma Control Test, Asthma Quality of Life Questionnaire, and Hospital
      Anxiety and Depression Scale. RESULTS: Insomnia (ISI >= 10) was identified in 263
      participants (37%). Presence of insomnia was associated with higher levels of
      depression and anxiety symptoms and poorer quality of life. Those with insomnia
      had a 2.4-fold increased risk for having not well-controlled asthma and a 1.5
      fold increased risk for asthma-related health care utilization in the past year
      compared with those without insomnia. CONCLUSIONS: Insomnia is highly prevalent
      in asthma and is associated with adverse outcomes. Further studies are needed to
      gain a better understanding of the interaction between insomnia and asthma
      control.

PMID- 27720883
TI  - Pediatric OSA Syndrome Morbidity Biomarkers: The Hunt Is Finally On!
AB  - Since initial reports 40 years ago on pediatric OSA syndrome (OSAS) as a distinct
      and prevalent clinical entity, substantial advances have occurred in the
      delineation of diagnostic and treatment approaches. However, despite emerging and
      compelling evidence that OSAS increases the risk for cognitive, cardiovascular,
      and metabolic end-organ morbidities, routine assessment of such morbidities is
      seldom conducted in clinical practice. One of the major reasons for such
      discrepancies resides in the relatively labor-intensive and onerous steps that
      would be required to detect the presence of any of such morbidities, further
      adding to the already elevated cost of diagnosing the disorder. To circumvent
      these obstacles, the search for biomarker signatures of pediatric OSA and its
      cognitive and cardiometabolic consequences was launched, and considerable
      progress has occurred since then. Here, we review the current evidence for the
      presence of morbidity-related biomarkers among children with OSAS, and explore
      future opportunities in this promising arena.

PMID- 27720886
TI  - Maternal cortical response to baby pain and postpartum depressive symptoms.
AB  - Decreased maternal empathic abilities toward infants have been reported with
      postpartum depression (PPD). The aims of this study were: (1) To identify
      mothers' cortical regions activated by the observation of their own newborn's
      pain; (2) To study the relation between such cortical activation and PPD
      symptoms. By optical topography, a functional neuroimaging system, we assessed
      mothers' cortical activation when watching their own newborns during a heel
      prick. PPD symptoms and newborn's pain expression were also assessed. Watching
      their newborn in pain activated mothers' left somatosensory cortex (P=0.003) and
      right superior temporal cortex (P=0.002). PPD score showed a negative correlation
      with left somatosensory cortex activation (rs=-0.41; P=0.026), that decreased as
      PPD symptoms increased. To conclude, an activation of cortical areas, previously
      associated with empathy for pain, can be demonstrated in the mother shortly after
      birth. Such response appeared to be dampened by PPD symptoms.

PMID- 27720885
TI  - C57BL/6 mice are resistant to joint degeneration induced by whole-body vibration.
AB  - OBJECTIVE: Whole-body vibration (WBV) platforms are commercially available
      devices that are used clinically to treat numerous musculoskeletal conditions
      based on their reported ability to increase bone mineral density and muscle
      strength. Despite widespread use, there is an alarming lack of understanding of
      the direct effects of WBV on joint health. Previous work by our lab demonstrated
      that repeated exposure to WBV using protocols that model those used clinically,
      induces intervertebral disc (IVD) degeneration and osteoarthritis-like damage in
      the knee of skeletally mature, male mice of a single outbred strain (CD-1). The
      present study examined whether exposure to WBV induces similar deleterious
      effects in a genetically different strain of mouse (C57BL/6). DESIGN: Male 10
      week-old C57BL/6 mice were exposed to vertical sinusoidal WBV for 30 min/day, 5
      days/week, for 4 or 8 weeks using previously reported protocols (45 Hz, 0.3 g
      peak acceleration). Following WBV, joint tissues were examined using histological
      analysis and gene expression was quantified using real-time PCR (qPCR). RESULTS:
      Our analyses show a lack of WBV-induced degeneration in either the knee or IVDs
      of C57BL/6 mice exposed to WBV for 4 or 8 weeks, in direct contrast to the WBV
      induced damage previously reported by our lab in CD-1 mice. CONCLUSIONS: Together
      with previous studies from our group, the present study demonstrates that the
      effects of WBV on joint tissues vary in a strain-specific manner. These findings
      highlight the need to examine genetic or physiological differences that may
      underlie susceptibility to the deleterious effects of WBV on joint tissues.

PMID- 27720887
TI  - ERCP for diagnosis and extraction of choledochal phytobezoar causing right upper
      quadrant abdominal pain and cholestasis in a patient without prior sphincterotomy
      or biliary instrumentation.

PMID- 27720888
TI  - Esophageal hemangiomatosis with chest CT revealing a fine, curvilinear, calcified
      thrombus within the esophagus simulating acute esophageal fishbone impaction:
      first reported endoscopic photograph of GI manifestations in Maffucci syndrome.

PMID- 27720889
TI  - Molecular evolution and phylogenetic analysis of biocontrol genes acquired from
      SCoT polymorphism of mycoparasitic Trichoderma koningii inhibiting phytopathogen
      Rhizoctonia solani Kuhn.
AB  - The biocontrol agent Trichoderma (T. harzianum, T. viride, T. virens, T.
      hamantum, T. koningii, T. pseudokoningii and Trichoderma species) inhibited
      variably (15.32 - 88.12%) the in vitro growth of Rhizoctonia solani causing root
      rot in cotton. The T. koningii MTCC 796 evidenced highest (88.12%) growth
      inhibition of test pathogen followed by T. viride NBAII Tv23 (85.34%). Scanning
      electron microscopic study confirmed mycoparasitism for MTCC 796 and Tv23 which
      were capable of completely overgrowing on R. solani by degrading mycelia, coiling
      around the hyphae with hook-like structures. The antagonists T. harzianum NBAII
      Th1 and, T. virens NBAII Tvs12 exhibited strong antibiosis and formed 2-4 mm zone
      of inhibition for 70.28% and 46.62%, respectively growth inhibition of test
      pathogen. Mycoparasitism is a strong mode of action for biocontrol activity
      compared with antibiosis. The antagonists Trichoderma strains were performed for
      start codon targeted (SCoT) polymorphism to acquire biocontrol genes from potent
      antagonist. The six unique SCoT fragments amplified by genomic DNA of best
      mycoparasitic antagonist MTCC 796 strain are subjected to DNA sequencing resulted
      to confirm two functional sequences for activity related to biocontrol genes. The
      phylogenetic and molecular evolution of functional 824 bp of SCoT-3(920) and 776
      bp of SCoT-6(806) fragments signify sequence homology with biocontrol genes
      endochitinase (partial cds of 203 amino acids) and novel hmgR genes (partial cds
      of 239 amino acids), respectively and the same were annotated and deposited in
      NCBI GenBank database. The hmgR gene is liable to be express hmg - CoA reductase
      which is a key enzyme for regulation of terpene biosynthesis and mycoparasitic
      strains produced triterpenes during antagonism to inhibit growth of fungal
      pathogen as evidenced with GC-MS profile. The biocontrol genes are found in best
      antagonist T. koningii MTCC 796 for mycoparasitic activity to restrain the growth
      of test pathogen R. solani.

PMID- 27720890
TI  - SIRT1 overexpression in cervical squamous intraepithelial lesions and invasive
      squamous cell carcinoma.
AB  - Invasive squamous cell carcinoma (SCC) of the cervix involves the progression of
      premalignant cervical intraepithelial neoplasia (CIN) and is associated with
      persistent human papillomavirus infection. Most CINs will regress, and the
      challenge is to identify the lesions likely to progress to invasive cancer. We
      evaluated Sirtuin 1 (SIRT1) expression in nonneoplastic cervix, CINs, and SCCs as
      a potential biomarker to predict disease progression. A total of 101 cases were
      selected including 29 CIN 1s, 32 CIN 2s, 16 CIN 3s, 2 microinvasive SCCs, and 22
      invasive SCCs. Cervical nonneoplastic squamous epithelium showed weak positivity
      of SIRT1 in the basal layer. SIRT1 cytoplasmic overexpression was found in 13.8%
      of CIN 1s (4/29), 40.6% of CIN 2s (13/32), and 50% of CIN 3s (8/16), and it was
      statistically significant between CIN 1 and CIN 2/3 lesions (P=.01). All 24 cases
      of invasive and microinvasive SCC showed SIRT1 overexpression, with 25% (6/24)
      showing cytoplasmic staining only, 4.2% (1/24) showing nuclear staining only, and
      70.8% (17/24) showing both nuclear and cytoplasmic staining. From CIN 1 to SCC,
      SIRT1 expression showed steady and statistically significant increase (CIN 1
      versus CIN 2-3, P=.01; CIN 2-3 versus SCC, P=.0001). Thus, SIRT1 may serve as a
      potential biomarker for predicting the progression of CIN to invasive SCC.

PMID- 27720891
TI  - Effects of competition outcome on testosterone concentrations in humans: An
      updated meta-analysis.
AB  - A contribution to a special issue on Hormones and Human Competition. Since
      Archer's (2006) influential meta-analysis, there has been a major increase in the
      number of studies investigating the effect of competition outcome on testosterone
      reactivity patterns in humans. Despite this increased research output, there
      remains debate as to whether competition outcome modulates testosterone
      concentrations. The present paper examines this question using a meta-analytic
      approach including papers published over the last 35years. Moreover, it provides
      the first meta-analytic estimate of the effect of competition outcome on
      testosterone concentrations in women. Results from a meta-analysis involving 60
      effect sizes and >2500 participants indicated that winners of a competition
      demonstrated a larger increase in testosterone concentrations relative to losers
      (D=0.20)-an effect that was highly heterogeneous. This 'winner-loser' effect was
      most robust in studies conducted outside the lab (e.g., in sport venues)
      (D=0.43); for studies conducted in the lab, the effect of competition outcome on
      testosterone reactivity patterns was relatively weak (D=0.08), and only found in
      studies of men (D=0.15; in women: D=-0.04). Further, the 'winner-loser' effect
      was stronger among studies in which pre-competition testosterone was sampled
      earlier than (D=0.38, after trim and fill correction) rather than within (D=0.09)
      10min of the start of the competition. Therefore, these results also provide
      important insight regarding study design and methodology, and will be a valuable
      resource for researchers conducting subsequent studies on the 'winner loser'
      effect.

PMID- 27720892
TI  - Carbon monoxide releasing molecule induces endothelial nitric oxide synthase
      activation through a calcium and phosphatidylinositol 3-kinase/Akt mechanism.
AB  - The production of nitric oxide (NO) by endothelial NO synthase (eNOS) plays a
      major role in maintaining vascular homeostasis. This study elucidated the
      potential role of carbon monoxide (CO)-releasing molecules (CORMs) in NO
      production and explored the underlying mechanisms in endothelial cells. We
      observed that 25MUM CORM-2 could increase NO production and stimulate an increase
      in the intracellular Ca2+ level. Furthermore, ethylene glycol-bis(beta-aminoethyl
      ether)-N,N,N',N'-tetra acetic acid caused CORM-2-induced NO production, which was
      abolished by 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid
      tetraacetoxy-methyl ester (BAPTA-AM), indicating that intracellular Ca2+ release
      plays a major role in eNOS activation. The inhibition of the IP3 receptor
      diminished the CORM-2-induced intracellular Ca2+ increase and NO production.
      Furthermore, CORM-2 induced eNOS Ser1179 phosphorylation and eNOS dimerization,
      but it did not alter eNOS expression. CORM-2 (25MUM) also prolonged Akt
      phosphorylation, lasting for at least 12h. Pretreatment with phosphatidylinositol
      3-kinase inhibitors (wortmannin or LY294002) inhibited the increases in NO
      production and phosphorylation but did not affect eNOS dimerization. CORM-2
      induced eNOS Ser1179 phosphorylation was intracellularly calcium-dependent,
      because pretreatment with an intracellular Ca2+ chelator (BAPTA-AM) inhibited
      this process. Although CORM-2 increases intracellular reactive oxygen species
      (ROS), pretreatment with antioxidant enzyme catalase and N-acetyl-cysteine did
      not abolish the CORM-2-induced eNOS activity or phosphorylation, signifying that
      ROS is not involved in this activity. Hence, CORM-2 enhances eNOS activation
      through intracellular calcium release, Akt phosphorylation, and eNOS
      dimerization.

PMID- 27720893
TI  - Aerobic exercise-related attenuation of arterial pulmonary hypertension: A right
      arrow targets the disease?
AB  - Characterized by progressive elevation of mean pulmonary artery pressure and
      pulmonary vascular resistance, pulmonary arterial hypertension (PAH) is an
      important health problem that contributes to right heart failure. Pulmonary
      arterial remodeling and constriction are two prominent features of PAH. It is a
      traditional view that increasing pulmonary blood flow and pressure, aerobic
      exercise does more harm than good to the pulmonary vasculature in PAH. However,
      recent studies have documented a potential benefit of low-intensity aerobic
      exercise for PAH patients. Here the current mini-review outlines the evidence and
      challenges for this additional tool in our armamentarium to combat this ominous
      disease.

PMID- 27720895
TI  - Stem cells and their role in pituitary tumorigenesis.
AB  - The presence of adult pituitary stem cells (PSCs) has been described in murine
      systems by comprehensive cellular profiling and genetic lineage tracing
      experiments. PSCs are thought to maintain multipotent capacity throughout life
      and give rise to all hormone-producing cell lineages, playing a role in pituitary
      gland homeostasis. Additionally, PSCs have been proposed to play a role in
      pituitary tumorigenesis, in both adenomas and adamantinomatous
      craniopharyngiomas. In this manuscript, we discuss the different approaches used
      to demonstrate the presence of PSCs in the murine adult pituitary, from marker
      analyses to genetic tracing. In addition, we review the published literature
      suggesting the existence of tumor stem cells in mouse and human pituitary tumors.
      Finally, we discuss the potential role of PSCs in pituitary tumorigenesis in the
      context of current models of carcinogenesis and present evidence showing that in
      contrast to pituitary adenoma, which follows a classical cancer stem cell
      paradigm, a novel mechanism has been revealed for paracrine, non-cell autonomous
      tumor initiation in adamantinomatous craniopharyngioma, a benign but clinically
      aggressive pediatric tumor.

PMID- 27720896
TI  - Genetic programs of the developing tuberal hypothalamus and potential mechanisms
      of their disruption by environmental factors.
AB  - The hypothalamus is a critical regulator of body homeostasis, influencing the
      autonomic nervous system and releasing trophic hormones to modulate the endocrine
      system. The developmental mechanisms that govern formation of the mature
      hypothalamus are becoming increasingly understood as research in this area grows,
      leading us to gain appreciation for how these developmental programs are
      susceptible to disruption by maternal exposure to endocrine disrupting chemicals
      or other environmental factors in utero. These vulnerabilities, combined with the
      prominent roles of the various hypothalamic nuclei in regulating appetite,
      reproductive behaviour, mood, and other physiologies, create a window whereby
      early developmental disruption can have potent long-term effects. Here we broadly
      outline our current understanding of hypothalamic development, with a particular
      focus on the tuberal hypothalamus, including what is know about nuclear
      coalescing and maturation. We finish by discussing how exposure to environmental
      or maternally-derived factors can perhaps disrupt these hypothalamic
      developmental programs, and potentially lead to neuroendocrine disease states.

PMID- 27720894
TI  - Melanoma antigen-A11 regulates substrate-specificity of Skp2-mediated protein
      degradation.
AB  - Melanoma antigen-A11 (MAGE-A11) is a proto-oncogene involved in androgen receptor
      signaling and androgen-dependent cell growth. In this report we provide evidence
      that MAGE-A11 interacts with Skp2 (S phase kinase-associated protein), the
      substrate recognition protein of the Skp1-Cullin1-F-box E3 ubiquitin ligase, and
      with Skp2 binding protein, cyclin A. A similar cyclin A binding motif in MAGE-A11
      and Skp2 was consistent with a competitive relationship between MAGE-A11 and Skp2
      in binding cyclin A. Skp2 inhibited MAGE-A11 interaction with cyclin A.
      Differential effects of MAGE-A11 on Skp2-mediated protein degradation were also
      revealed. MAGE-A11 increased Skp2-mediated degradation of cyclin A and
      retinoblastoma-related protein p130. In contrast, MAGE-A11 decreased Skp2
      mediated degradation of E2F1 and Skp2 self-ubiquitination. Stabilization of E2F1
      by MAGE-A11 was associated with sequestration and inactivation of Skp2 through
      the formation of an E2F1-MAGE-A11-Skp2 complex. We conclude that direct
      interactions of MAGE-A11 with Skp2 and cyclin A regulate the substrate
      specificity of Skp2-mediated protein degradation.

PMID- 27720897
TI  - Cell type-specific and common characteristics of exosomes derived from mouse cell
      lines: Yield, physicochemical properties, and pharmacokinetics.
AB  - Exosomes are small membrane vesicles secreted from cells and are expected to be
      used as drug delivery systems. Important characteristics of exosomes, such as
      yield, physicochemical properties, and pharmacokinetics, may be different among
      different cell types. However, there is limited information about the effect of
      cell type on these characteristics. In the present study, we evaluated these
      characteristics of exosomes derived from five different types of mouse cell
      lines: B16BL6 murine melanoma cells, C2C12 murine myoblast cells, NIH3T3 murine
      fibroblasts cells, MAEC murine aortic endothelial cells, and RAW264.7 murine
      macrophage-like cells. Exosomes were collected using a differential
      ultracentrifugation method. The exosomes collected from all the cell types were
      negatively charged globular vesicles with a diameter of approximately 100nm.
      C2C12 and RAW264.7 cells produced more exosomes than the other types of cells.
      The exosomes were labeled with a fusion protein of Gaussia luciferase and
      lactadherin to evaluate their pharmacokinetics. After intravenous injection into
      mice, all the exosomes rapidly disappeared from the systemic circulation and
      mainly distributed to the liver. In conclusion, the exosome yield was
      significantly different among the cell types, and all the exosomes evaluated in
      this study showed comparable physicochemical and pharmacokinetic properties.

PMID- 27720898
TI  - The isolated perfused human skin flap model: A missing link in skin penetration
      studies?
AB  - Development of effective (trans)dermal drug delivery systems requires reliable
      skin models to evaluate skin drug penetration. The isolated perfused human skin
      flap remains metabolically active tissue for up to 6h during in vitro perfusion.
      We introduce the isolated perfused human skin flap as a close-to-in vivo skin
      penetration model. To validate the model's ability to evaluate skin drug
      penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine)
      fluorescence marker were applied. The skin flaps were perfused with modified
      Krebs-Henseleit buffer (pH7.4). Infrared technology was used to monitor perfusion
      and to select a well-perfused skin area for administration of the markers. Flap
      perfusion and physiological parameters were maintained constant during the 6h
      experiments and the amount of markers in the perfusate was determined. Calcein
      was detected in the perfusate, whereas rhodamine was not detectable. Confocal
      images of skin cross-sections shoved that calcein was uniformly distributed
      through the skin, whereas rhodamine accumulated in the stratum corneum. For
      comparison, the penetration of both markers was evaluated on ex vivo human skin,
      pig skin and cellophane membrane. The proposed perfused flap model enabled us to
      distinguish between the penetrations of the two markers and could be a promising
      close-to-in vivo tool in skin penetration studies and optimization of
      formulations destined for skin administration.

PMID- 27720899
TI  - Identification of novel peptides against TNF-alpha using phage display technique
      and in silico modeling of their modes of binding.
AB  - The aim of this study was to identify novel TNF-alpha blocking peptide(s) using
      phage display technology. Two novel 7-mer TNF-alpha binding peptides P51 and P52
      with Kd values of 1.47 and 0.51nM were identified. Phage particles displaying P51
      and P52 peptides at 0.318nM concentration prevent cytotoxic effect of TNF-alpha
      on L929 cells by 8.2% and 16.15%, respectively. Synthesized P51 and P52 peptides
      also inhibited TNF-alpha induced cytotoxicity with IC50 values of 25.15+/-2.18
      and 7.08+/-2.24MUM, respectively. The result of RT-PCR also supports the
      inhibitory activity of the identified peptides, where P51 and P52 significantly
      inhibit the inductive effect of TNF-alpha on IkappaB-alpha mRNA levels. The
      inhibitory effects of the peptides were attributed to their abilities of binding
      at the inter-subunit interfaces leading to TNF-alpha dissociation. The results of
      molecular docking studies revealed that the peptides-TNF-alpha complexes are
      mostly stabilized by hydrophobic contacts.

PMID- 27720900
TI  - Robust at-line quantification of poly(3-hydroxyalkanoate) biosynthesis by flow
      cytometry using a BODIPY 493/503-SYTO 62 double-staining.
AB  - Poly(3-hydroxyalkanoates) (PHAs) are bio-based and biodegradable polyesters which
      have been considered as a promising alternative to petrol-based plastics. Their
      bacterial production is a dynamic process in which intracellular polymerization
      and depolymerization are closely linked and depend on the availability of carbon
      substrates and other nutrients. These dynamics require a fast and quantitative
      method to determine the optimal harvest-time of PHA containing cells or to adjust
      carbon supply. In principle, flow cytometry (FCM) is an ideal tool that suits
      these requirements and, in addition, provides data on the PHA content of
      different cell populations. However, FCM-based PHA quantification methods have
      often relied on laborious sample preparation including washing steps and long
      incubation times. Here, we introduce a fast method based on double-staining using
      BODIPY 493/503 for PHA staining and SYTO 62 for DNA that allows acquiring
      reliable fluorescence and cell count data in <10min. Finally, fed-batch
      experiments with Pseudomonas putida KT2440 and Rhodospirillum rubrum S1 revealed
      that the method was robust and independent of the strain and type of PHA (medium
      chain-length [mcl-] and short-chain-length [scl-] PHA, respectively).
      Interestingly, the specific PHA fluorescence was in case of mcl-PHA larger than
      for scl-PHA, probably reflecting the different material properties (e.g.,
      specific density, hydrophilicity and crystallinity).

PMID- 27720901
TI  - Guarana (Paullinia cupana) ameliorates memory impairment and modulates
      acetylcholinesterase activity in Poloxamer-407-induced hyperlipidemia in rat
      brain.
AB  - Hyperlipidemia is a risk factor for the development of cognitive dysfunction and
      atherosclerosis. Natural compounds have recently received special attention in
      relation to the treatment of disease due to their low cost and wide margin of
      safety. Thus, the aim of this study was to determine the possible preventive
      effect of guarana powder (Paullinia cupana) on memory impairment and
      acetylcholinesterase (AChE) activity in the brain structures of rats with
      Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with
      guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a
      period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative
      standard. Acute hyperlipidemia was induced with intraperitoneal injections of
      500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were
      performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were
      separated to assess acetylcholinesterase activity. Our results revealed that
      guarana powder was able to reduce the levels of TC and LDL-C in a manner similar
      to simvastatin. Guarana powder also partially reduced the liver damage caused by
      hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and
      improve memory impairment due to hyperlipidemia. Guarana powder may therefore be
      a source of promising phytochemicals that can be used as adjuvant therapy in the
      management of hyperlipidemia and cognitive disorders.

PMID- 27720902
TI  - Targeted Differentiation of Regional Ventral Neuroprogenitors and Related
      Neuronal Subtypes from Human Pluripotent Stem Cells.
AB  - Embryoid body (EB) formation and adherent culture (AD) paradigms are equivalently
      thought to be applicable for neural specification of human pluripotent stem
      cells. Here, we report that sonic hedgehog-induced ventral neuroprogenitors under
      EB conditions are fated to medial ganglionic eminence (MGE), while the AD cells
      mostly adopt a floor-plate (FP) fate. The EB-MGE later on differentiates into
      GABA and cholinergic neurons, while the AD-FP favors dopaminergic neuron
      specification. Distinct developmental, metabolic, and adhesion traits in AD and
      EB cells may potentially account for their differential patterning potency. Gene
      targeting combined with small-molecule screening experiments identified that
      concomitant inhibition of Wnts, STAT3, and p38 pathways (3i) could largely
      convert FP to MGE under AD conditions. Thus, differentiation paradigms and
      signaling regulators can be integrated together to specify distinct neuronal
      subtypes for studying and treating related neurological diseases, such as
      epilepsy, Alzheimer's disease, and Parkinson's disease.

PMID- 27720903
TI  - Early Development of Definitive Erythroblasts from Human Pluripotent Stem Cells
      Defined by Expression of Glycophorin A/CD235a, CD34, and CD36.
AB  - The development of human erythroid cells has been mostly examined in models of
      adult hematopoiesis, while their early derivation during embryonic and fetal
      stages is largely unknown. We observed the development and maturation of
      erythroblasts derived from human pluripotent stem cells (hPSCs) by an efficient
      co-culture system. These hPSC-derived early erythroblasts initially showed
      definitive characteristics with a glycophorin A+ (GPA+) CD34lowCD36- phenotype
      and were distinct from adult CD34+ cell-derived ones. After losing CD34
      expression, early GPA+CD36- erythroblasts matured into GPA+CD36low/+ stage as the
      latter expressed higher levels of beta-globin along with a gradual loss of
      mesodermal and endothelial properties, and terminally suppressed CD36. We
      establish a unique in vitro model to trace the early development of hPSC-derived
      erythroblasts by serial expression of CD34, GPA, and CD36. Our findings may
      provide insight into the understanding of human early erythropoiesis and,
      ultimately, therapeutic potential.

PMID- 27720904
TI  - Endogenous DNA Damage Leads to p53-Independent Deficits in Replicative Fitness in
      Fetal Murine Fancd2-/- Hematopoietic Stem and Progenitor Cells.
AB  - Our mechanistic understanding of Fanconi anemia (FA) pathway function in
      hematopoietic stem and progenitor cells (HSPCs) owes much to their role in
      experimentally induced DNA crosslink lesion repair. In bone marrow HSPCs,
      unresolved stress confers p53-dependent apoptosis and progressive cell attrition.
      The role of FA proteins during hematopoietic development, in the face of
      physiological replicative demand, remains elusive. Here, we reveal a fetal HSPC
      pool in Fancd2-/- mice with compromised clonogenicity and repopulation. Without
      experimental manipulation, fetal Fancd2-/- HSPCs spontaneously accumulate DNA
      strand breaks and RAD51 foci, associated with a broad transcriptional DNA-damage
      response, and constitutive activation of ATM as well as p38 stress kinase.
      Remarkably, the unresolved stress during rapid HSPC pool expansion does not
      trigger p53 activation and apoptosis; rather, it constrains proliferation.
      Collectively our studies point to a role for the FA pathway during hematopoietic
      development and provide a new model for studying the physiological function of FA
      proteins.

PMID- 27720907
TI  - Molecular beacons with JOE dye: Influence of linker and 3' couple quencher.
AB  - Molecular beacons carrying JOE dye (4',5'-dichloro-2',7'-dimethoxy-6
      carboxyfluorescein) on a rigid or flexible linker and one or two BHQ1 quenchers
      have been prepared and tested in real-time PCR using Fusarium avenaceum
      elongation factor 1alpha DNA template. The probes were different in their
      structures (loop size and stem length), linkers for dye attachment (6
      aminohexanol or trans-4-aminocyclohexanol), quencher composition (single and
      double BHQ1) to elucidate the influence of all these features. Fluorogenic
      properties of the probes were studied and compared to those of FAM (fluorescein)
      based probes. All the factors - stem length, JOE vs FAM, rigid vs flexible
      linker, single vs double quencher - appeared to play a considerable role in the
      probe's fluorescent properties and determine the usability of the probe at two
      different temperatures of fluorescence detection (55 degrees S and 64 degrees S).

PMID- 27720906
TI  - Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs
      Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling.
AB  - The transition of human embryonic stem cells (hESCs) from pluripotency to lineage
      commitment is not fully understood, and a role for phenotypic transcription
      factors in the initial stages of hESC differentiation remains to be explored.
      From a screen of candidate factors, we found that RUNX1 is selectively and
      transiently upregulated early in hESC differentiation to mesendodermal lineages.
      Transcriptome profiling and functional analyses upon RUNX1 depletion established
      a role for RUNX1 in promoting cell motility. In parallel, we discovered a loss of
      repression for several epithelial genes, indicating that loss of RUNX1 impaired
      an epithelial to mesenchymal transition during differentiation. Cell biological
      and biochemical approaches revealed that RUNX1 depletion specifically compromised
      TGFB2 signaling. Both the decrease in motility and deregulated epithelial marker
      expression upon RUNX1 depletion were rescued by reintroduction of TGFB2, but not
      TGFB1. These findings identify roles for RUNX1-TGFB2 signaling in early events of
      mesendodermal lineage commitment.

PMID- 27720908
TI  - Molecular detection of Mycoplasma haemomuris subspecies using dnaK-targeted real
      time PCR with SYBR Green I and melting curve analysis.
AB  - Hemoplasmas cause severe infections in mammals, but these pathogens are difficult
      to detect and identify at the species and subspecies level because of the need
      for time-consuming sequence based methods. Here, we used real-time PCR with SYBR
      Green I targeting of the dnaK gene followed by standard melting curve analysis to
      achieve rapid detection and differentiation of the Mycoplasma haemomuris
      subspecies 'Candidatus Mycoplasma haemomuris subsp. musculi' and 'Candidatus M.
      haemomuris subsp. ratti'. The melting temperatures of the PCR products, 84.63 +/-
      0.14  degrees C for 'Candidatus M. haemomuris subsp. musculi', and 80.72 +/- 0.16
      degrees C for 'Candidatus M. haemomuris subsp. ratti', provided clear
      differentiation between them. Murine hemoplasma DNA samples, which were used as
      references, were confirmed for species by an analysis of 16S rRNA sequences. The
      protocol described herein provides a new rapid detection and identification
      method suitable for use with two recognized subspecies of M. haemomuris.

PMID- 27720905
TI  - A Dynamic WNT/beta-CATENIN Signaling Environment Leads to WNT-Independent and WNT
      Dependent Proliferation of Embryonic Intestinal Progenitor Cells.
AB  - Much of our understanding about how intestinal stem and progenitor cells are
      regulated comes from studying the late fetal stages of development and the adult
      intestine. In this light, little is known about intestine development prior to
      the formation of stereotypical villus structures with columnar epithelium, a
      stage when the epithelium is pseudostratified and appears to be a relatively
      uniform population of progenitor cells with high proliferative capacity. Here, we
      investigated a role for WNT/beta-CATENIN signaling during the pseudostratified
      stages of development (E13.5, E14.5) and following villus formation (E15.5) in
      mice. In contrast to the well-described role for WNT/beta-CATENIN signaling as a
      regulator of stem/progenitor cells in the late fetal and adult gut, conditional
      epithelial deletion of beta-catenin or the Frizzled co-receptors Lrp5 and Lrp6
      had no effect on epithelial progenitor cell proliferation in the pseudostratified
      epithelium. Mutant embryos displayed obvious developmental defects, including
      loss of proliferation and disruptions in villus formation starting only at E15.5.
      Mechanistically, our data suggest that WNT signaling-mediated proliferation at
      the time of villus formation is driven by mesenchymal, but not epithelial, WNT
      ligand secretion.

PMID- 27720909
TI  - Mercury sulfides are much less nephrotoxic than mercury chloride and
      methylmercury in mice.
AB  - Mercury sulfides (alpha-HgS, beta-HgS) are frequently included in traditional
      medicines. Mercury is known for nephrotoxicity, their safety is of concern. To
      address this question, mice were orally administrated with Zuotai (54% beta-HgS,
      30mg/kg), alpha-HgS (HgS, 30mg/kg), HgCl2 (33.6mg/kg), or MeHgCl (3.1mg/kg) for
      7days, and nephrotoxicity was examined. Animal body weights were decreased by
      HgCl2 and to a lesser extent by MeHg, but unaltered after Zuotai and HgS. HgCl2
      and MeHg produced renal tubular vacuolation, interstitial inflammation and cell
      degeneration with protein cysts in the tubular lumen, while these pathological
      lesions were mild in Zuotai and HgS-treated mice. Electron microscopy showed that
      HgCl2 and MeHg produced spotted swelling endothelium reticulum, while these
      lesions were mild or absent in Zuotai and HgS-treated mice. Renal Hg contents
      reached 250-300ng/mg kidney in HgCl2 and MeHg groups as compared to 2-3ng/mg in
      Zuotai and HgS groups. The expression of kidney injury biomarkers, kidney injury
      molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (Ngal), were
      increased after HgCl2 and MeHg, but unaltered after Zuotai and HgS. The
      expression of renal influx transporters Oat3 and Oatp4c1 was decreased, while the
      expression of renal efflux transporter such as Mrp2, Mrp4, and Mate2 was
      increased following HgCl2 and MeHg. These gene expressions were unchanged after
      Zuotai and HgS. In summary, both alpha-HgS and beta-HgS are less nephrotoxic than
      HgCl2 and MeHg, indicating that chemical forms of mercury are a major determinant
      of mercury disposition and toxicity.

PMID- 27720911
TI  - Predicted Increases in Incidence of Colorectal Cancer in Developed and Developing
      Regions, in Association With Ageing Populations.
AB  - BACKGROUND & AIMS: Population growth and changes in demographic structure are
      linked to trends in colorectal cancer (CRC) incidence. The aim of this study is
      to estimate future CRC incidence in the ageing population, and compare trends
      across developing and developed regions. METHODS: Cancer and population data were
      extracted from the International Agency for Research on Cancer. Annual incidence
      rates for the major types of cancer in 118 selected populations were extracted
      from 102 cancer registries in 39 countries worldwide. We selected 8 jurisdictions
      (from the United States, Europe, and Asia) that reported 20-year cancer incidence
      rates since 1988. Time series models were constructed to project cancer
      incidence, by sex and age, to 2030. Incidence rates for persons older than 65
      years were combined and further adjusted for change of ageing population. We
      compared age-adjusted incidence rates among the jurisdictions. RESULTS: The total
      population older than 65 years old was 12,917,794 in 1988, and the number
      increased by almost 40% to 17,950,115 in 2007. In developed countries in the West
      CRC incidence is predicted to decrease by 16.3% in the United States, increase by
      4.8% in the United Kingdom, and increase by 4.7% in Sweden by 2030. In developing
      countries, such as China (Shanghai), Croatia, and Costa Rica, CRC incidence is
      predicted to increase in a steep curve by 2030 because of the growing population
      and ageing effect; in 2030, the incidence increases were 60.5% for China, 47.0%
      for Croatia, and 18.5% for Costa Rica. We also predict CRC incidence will
      increase greatly by 2030 in Japan and Hong Kong, which are developed regions.
      CONCLUSIONS: With the exception of the United States, the incidence of CRC is
      expected to continue to rise in most regions in the coming decades, due to
      population growth and changes in demographic structure. The predicted increases
      are more marked in developing regions with limited health care resources.

PMID- 27720910
TI  - Implementing the Concept of Continuous Clinical Response Into Clinical Practice
      for Ulcerative Colitis.
AB  - BACKGROUND & AIMS: Ulcerative colitis (UC) is a complex and progressive disease
      that has a significant humanistic and economic impact in patients and the wider
      society. Disease control is still an unmet need for a large proportion of
      patients. The aim of this article was to review the current evidence to assess
      the feasibility, value, and impact of integrating continuous clinical response
      (CCR) as a patient-reported outcome into routine management of UC. METHODS:
      Literature searches in PubMed, Google Scholar, and conference proceedings were
      undertaken to retrieve the relevant articles regarding burden and course of
      disease, outcome measures in UC, tools for measuring disease activity, and models
      for patient's self-monitoring. RESULTS: The concept of CCR was first introduced
      during the PURSUIT-M trial, where evidence was provided to support the clinical
      and quality of life benefits of achieving CCR. However, patient monitoring as
      implemented during the trial was not feasible for its use in the real world.
      Thus, a simple self-reported score (eg, PRO2) to monitor CCR, with good
      correlation with more complex procedure-driven indices, was identified for its
      use in routine patient care. Feasibility of introducing this easy-to-use tool
      over time as an integral part of patient management was also explored.
      CONCLUSIONS: The introduction of CCR as a management goal for UC patients may
      pose the step change needed to improve disease course and patient's life.
      Providing patients with simple tools to continuously monitor their disease
      activity is the first step for an integrated self-monitoring model of care in UC.

PMID- 27720912
TI  - Can Thiopurines Prevent Formation of Antibodies Against Tumor Necrosis Factor
      Antagonists After Failure of These Therapies?

PMID- 27720914
TI  - Delineating the Phenotypic Spectrum of the NTHL1-Associated Polyposis.

PMID- 27720913
TI  - High-resolution Anorectal Manometry for Identifying Defecatory Disorders and
      Rectal Structural Abnormalities in Women.
AB  - BACKGROUND & AIMS: Contrary to conventional wisdom, the rectoanal gradient during
      evacuation is negative in many healthy people, undermining the utility of
      anorectal high-resolution manometry (HRM) for diagnosing defecatory disorders. We
      aimed to compare HRM and magnetic resonance imaging (MRI) for assessing rectal
      evacuation and structural abnormalities. METHODS: We performed a retrospective
      analysis of 118 patients (all female; 51 with constipation, 48 with fecal
      incontinence, and 19 with rectal prolapse; age, 53 +/- 1 years) assessed by HRM,
      the rectal balloon expulsion test (BET), and MRI at Mayo Clinic, Rochester,
      Minnesota, from February 2011 through March 2013. Thirty healthy asymptomatic
      women (age, 37 +/- 2 years) served as controls. We used principal components
      analysis of HRM variables to identify rectoanal pressure patterns associated with
      rectal prolapse and phenotypes of patients with prolapse. RESULTS: Compared with
      patients with normal findings from the rectal BET, patients with an abnormal BET
      had lower median rectal pressure (36 vs 22 mm Hg, P = .002), a more negative
      median rectoanal gradient (-6 vs -29 mm Hg, P = .006) during evacuation, and a
      lower proportion of evacuation on the basis of MRI analysis (median of 40% vs
      80%, P < .0001). A score derived from rectal pressure and anorectal descent
      during evacuation and a patulous anal canal was associated (P = .005) with large
      rectoceles (3 cm or larger). A principal component (PC) logistic model
      discriminated between patients with and without prolapse with 96% accuracy. Among
      patients with prolapse, there were 2 phenotypes, which were characterized by high
      (PC1) or low (PC2) anal pressures at rest and squeeze along with higher rectal
      and anal pressures (PC1) or a higher rectoanal gradient during evacuation (PC2).
      CONCLUSIONS: In a retrospective analysis of patients assessed by HRM,
      measurements of rectal evacuation by anorectal HRM, BET, and MRI were correlated.
      HRM alone and together with anorectal descent during evacuation may identify
      rectal prolapse and large rectoceles, respectively, and also identify unique
      phenotypes of rectal prolapse.

PMID- 27720915
TI  - Validation of a Staging System for Acute Kidney Injury in Patients With Cirrhosis
      and Association With Acute-on-Chronic Liver Failure.
AB  - BACKGROUND & AIMS: In patients with cirrhosis of the liver, acute kidney injury
      (AKI) is classified into 3 stages. Recent studies indicate that there are 2
      subgroups of stage 1 disease, associated with different outcomes and serum levels
      of creatinine (SCr): stage 1A (SCr <1.5 mg/dL) and stage 1B (SCr >=1.5 mg/dL). We
      performed a prospective study to validate, in a large series of patients with
      cirrhosis, the association between this new description and patient outcomes, and
      assess the relationship between AKI stage and the presence of acute-on-chronic
      liver failure. METHODS: We collected data from 547 consecutive patients admitted
      for cirrhosis with acute decompensation to 2 tertiary hospitals (Italy and
      Spain), from February 2011 through June 2015. A total of 290 patients had AKI
      (53%; 197 had stage 1 disease); AKI stages were determined based on levels of SCr
      at diagnosis. Patients were followed up until death, liver transplantation, or
      for 90 days. The primary outcome was 90-day survival; secondary outcomes were
      progression and resolution of AKI and association with acute-on-chronic liver
      failure. RESULTS: Based on level of sCr at diagnosis, 58 patients had stage 1A
      disease and 139 had stage 1B disease. Of patients with stage 1A disease, 82%
      survived for 90 days; of patients with stage 1B disease, 55% survived for 90 days
      (P = .001). Hepatorenal syndrome and acute tubular necrosis were the most common
      causes of stage 1B AKI, and hypovolemia was the most common cause of stage 1A
      AKI. AKI progressed in a higher proportion of patients with 1B than 1A AKI (31%
      vs 15%; P = .017) and resolved in a higher proportion of patients with 1A disease
      (90% vs 52% of patients with stage 1B; P < .001). Stage 1B disease, but not 1A,
      was an independent predictor of AKI progression and mortality. ACLF developed in
      a significantly greater proportion of patients with stage 1B disease (76%) than
      stage 1A disease (22%; P < .001), which could account for the poor outcomes of
      patients with stage 1B disease. CONCLUSIONS: In a large group of patients with
      decompensated cirrhosis, we validated the association between AKI stages IA and
      IB (based on level of sCR) with survival times and AKI progression. We also
      associated these subgroups of AKI with development of acute-on-chronic liver
      failure. These findings are important for management of patients with
      decompensated cirrhosis.

PMID- 27720917
TI  - Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain
      in a Phase 2 Placebo-controlled Study.
AB  - BACKGROUND & AIMS: Delta-9-tetrahydrocannabinol (THC) is the most abundant
      cannabinoid from the plant Cannabis sativa. There is only equivocal evidence that
      THC has analgesic effects. We performed a phase 2 controlled trial to evaluate
      the analgesic efficacy, pharmacokinetics, safety, and tolerability of an oral
      tablet containing purified THC in patients with chronic abdominal pain. METHODS:
      Sixty-five patients with chronic abdominal pain for 3 months or more (numeric
      rating scale scores of 3 or more) after surgery or because of chronic
      pancreatitis were randomly assigned to groups given the THC tablet or identical
      matching placebos for 50-52 days. Subjects in the THC group were given the tablet
      first in a step-up phase (3 mg 3 times daily for 5 days and then 5 mg 3 times
      daily for 5 days), followed by a stable dose phase (8 mg 3 times daily until days
      50-52). Preceding and during the entire study period, patients were asked to
      continue taking their medications (including analgesics) according to
      prescription. Patients reported any additional pain medications in a diary.
      Efficacy and safety assessments were conducted preceding medication intake (day
      1), after 15 days, and at 50-52 days. Plasma samples were collected on study days
      1, 15, and 50-52; mean plasma concentration curves of THC and 11-OH-THC were
      plotted. The primary end point was pain relief, which was measured by a visual
      analogue scale (VAS) of the mean pain (VAS mean scores) on the basis of
      information from patient diaries. Secondary end points included pain and quality
      of life (determined from patient questionnaires), pharmacokinetics, and safety.
      RESULTS: At days 50-52, VAS mean scores did not differ significantly between the
      THC and placebo groups (F1,46 = 0.016; P = .901). Between the start and end of
      the study, VAS mean scores decreased by 1.6 points (40%) in the THC group
      compared with 1.9 points (37%) in the placebo group. No differences were observed
      in secondary outcomes. Oral THC was generally well-absorbed. Seven patients in
      the THC group stopped taking the tablets because of adverse events, compared with
      2 patients in the placebo group. All (possibly) related adverse events were mild
      or moderate. CONCLUSIONS: In a phase 2 study, we found no difference between a
      THC tablet and a placebo tablet in reducing pain measures in patients with
      chronic abdominal pain. THC, administered 3 times daily, was safe and well
      tolerated during a 50-day to 52-day treatment period. ClinicalTrials.gov number:
      NCT01562483 and NCT01551511.

PMID- 27720916
TI  - Hepatic Encephalopathy Is Associated With Mortality in Patients With Cirrhosis
      Independent of Other Extrahepatic Organ Failures.
AB  - BACKGROUND & AIMS: Although survival times have increased for patients with
      cirrhosis, hepatic encephalopathy (HE) remains a major complication and its
      relative contribution toward mortality in North America is unclear. We
      investigated whether HE is associated with mortality independent of extrahepatic
      organ failures (EHOFs). METHODS: We collected data from the North American
      Consortium for Study of End-stage Liver Disease database of hospitalized patients
      with cirrhosis at tertiary-care centers. EHOFs were defined as need for
      ventilation (respiratory failure), dialysis (renal failure), or shock
      (circulatory failure). We analyzed in-hospital and 30-day mortality for patients
      with varying HE grades and EHOF using adjusted models. RESULTS: We analyzed data
      from 1560 patients, 516 with HE (371 grade 1-2 and 145 grade 3-4). Patients with
      maximum HE grade 3-4 HE during hospitalization had a higher median model for end
      stage liver disease (MELD) score (22) than patients with HE grade 1-2 (MELD
      score, 19) or no HE (MELD score, 18) (P < .0001). Thirty-day mortality for
      patients with HE grade 3-4 was significantly higher (38%) than for patients with
      HE grade 1-2 (8%) or no HE (7%). A total of 107 patients had 2 or more EHOFs,
      with or without HE; 151 had 1 EHOF and 1302 had no organ failure. Unadjusted
      mortality was highest for patients with HE of grade 3-4 with 2 EHOFs (n = 44). On
      regression analysis, HE severity was significantly associated with in-hospital
      and 30-day mortality, independent of any EHOF, white blood cell count, systemic
      inflammatory response syndrome, or MELD score (odds ratio, 3.3; P < .0001).
      CONCLUSIONS: In an analysis of more than 1500 patients hospitalized for
      cirrhosis, HE of grade 3 or 4 was associated with higher in-hospital and 30-day
      mortality, independently of failure of other organs.

PMID- 27720919
TI  - Evaluation of the Tobacco Heating System 2.2. Part 2: Chemical composition,
      genotoxicity, cytotoxicity, and physical properties of the aerosol.
AB  - The chemical composition, in vitro genotoxicity, and cytotoxicity of the
      mainstream aerosol from the Tobacco Heating System 2.2 (THS2.2) were compared
      with those of the mainstream smoke from the 3R4F reference cigarette. In contrast
      to the 3R4F, the tobacco plug in the THS2.2 is not burnt. The low operating
      temperature of THS2.2 caused distinct shifts in the aerosol composition compared
      with 3R4F. This resulted in a reduction of more than 90% for the majority of the
      analyzed harmful and potentially harmful constituents (HPHCs), while the mass
      median aerodynamic diameter of the aerosol remained similar. A reduction of about
      90% was also observed when comparing the cytotoxicity determined by the neutral
      red uptake assay and the mutagenic potency in the mouse lymphoma assay. The
      THS2.2 aerosol was not mutagenic in the Ames assay. The chemical composition of
      the THS2.2 aerosol was also evaluated under extreme climatic and puffing
      conditions. When generating the THS2.2 aerosol under "desert" or "tropical"
      conditions, the generation of HPHCs was not significantly modified. When using
      puffing regimens that were more intense than the standard Health Canada Intense
      (HCI) machine-smoking conditions, the HPHC yields remained lower than when
      smoking the 3R4F reference cigarette with the HCI regimen.

PMID- 27720920
TI  - Antispasmodic effect of selected Citrus flavonoids on rat isolated jejunum
      specimens.
AB  - Citrus flavonoids are acknowledged for numerous pharmacological activities,
      including the myorelaxant effect on various smooth muscles. However, there is no
      data on their effect on jejunum contractility. Therefore, the aim of the study at
      hand was to evaluate the impact of hesperetin and diosmetin along with their
      glycosides on the motoric activity of intestine and to verify the possible
      mechanism of hesperetin-induced effect. The experiments were performed on rat
      isolated jejunum strips and were conducted under isometric conditions. Hesperetin
      and diosmetin, but not hesperidin and diosmin, dose-dependently (10-100uM) and
      reversibly inhibited acetylcholine (1uM) and KCl (80mM) induced contractile
      activity. The antispasmodic effect of hesperetin was partially blocked by 4
      aminopyridine (100uM), glibenclamide (100uM) and NG-nitro-L-arginine methyl ester
      (L-NAME, 100uM). By contrast, apamin (0.1uM), tetraethylammonium (500uM) and
      methylene blue (10uM) did not affect the magnitude of hesperetin-induced
      myorelaxant effect. Indomethacin (10uM) increased the force of hesperetin-evoked
      reaction. In conclusion, hesperetin and diosmetin are potent myorelaxant agents.
      The antispasmodic effect of hesperetin is partially mediated by fast current low
      voltage activated K+ channels, voltage-independent K+ channels and involves the
      nitric oxide pathway. Finally, hesperetin shows a synergistic effect with
      indomethacin towards jejunal KCl-precontracted smooth muscle.

PMID- 27720918
TI  - Methylmercury induces an initial increase in GABA-evoked currents in Xenopus
      oocytes expressing alpha1 and alpha6 subunit-containing GABAA receptors.
AB  - Early onset effects of methylmercury (MeHg) on recombinant alpha1beta2gamma2S or
      alpha6beta2gamma2S subunit-containing GABAA receptors were examined. These are
      two of the most prevalent receptor types found in cerebellum-a consistent target
      of MeHg-induced neurotoxicity. Heterologously expressed receptors were used in
      order to: (1) isolate receptor-mediated events from extraneous effects of MeHg
      due to stimulation of the receptor secondary to increased release of GABA seen
      with MeHg in neurons in situ and (2) limit the phenotypes of GABAA receptors
      present at one time. Initial changes in IGABA in Xenopus laevis oocytes
      expressing either alpha1beta2gamma2S or alpha6beta2gamma2S receptors were
      compared during continuous bath application of MeHg. A time-dependent increase in
      IGABA mediated by both receptor subtypes occurred following the first 25-30min of
      MeHg (5MUM) exposure. In alpha6beta2gamma2S containing receptors, the MeHg
      induced increase in IGABA was less pronounced compared to that mediated by
      alpha1beta2gamma2S containing receptors, although the pattern of effects was
      generally similar. Washing with MeHg-free solution reversed the increase in
      current amplitude. Application of bicuculline at the time of peak potentiation of
      IGABA rapidly and completely reversed the MeHg-induced currents. Therefore these
      MeHg-increased inward currents are mediated specifically by the two subtypes of
      GABAA receptors and appear to entail direct actions of MeHg on the receptor.
      However bicuculline did not affect stimulation by MeHg of oocyte endogenous Cl- 
      mediated current, which presumably results from increased [Ca2+]i. Thus, MeHg
      initially potentiates IGABA in oocytes expressing either alpha1beta2gamma2S or
      alpha6beta2gamma2S receptors prior to its more defined later effects, suggesting
      that MeHg may initially interact directly with GABAA receptors in a reversible
      manner to cause this potentiation.

PMID- 27720921
TI  - Hesperidin derivative-11 inhibits fibroblast-like synoviocytes proliferation by
      activating Secreted frizzled-related protein 2 in adjuvant arthritis rats.
AB  - Hesperidin (HDN), a flavanone glycoside derived from the citrus cultivation, has
      a multitude of pharmacological properties, which include antioxidant, anti
      inflammatory, hypolipidaemic and anti-carcinogenic actions, but the underlying
      mechanisms by which treatment of HDN attenuates Rheumatoid Arthritis (RA) remain
      elusive. Here we engaged to determine whether Hesperidin derivative-11(HDND-11),
      a HDN derivative with enhanced water-solubility and bioavailability, is effective
      on treating arthritis in rats. In this study, results of 3-(4, 5-dimethylthiazol
      2-yl)-2, 5-diphenyltetra-zolium bromide (MTT) assay and Flow cytometry indicated
      that administration of HDND-11 inhibited proliferation of fibroblast-like
      synoviocytes (FLS). Results of Western blot, Real-time quantitative PCR (RT-qPCR)
      analysis and Immunofluorescence staining demonstrated that HDND-11 was able to up
      regulate the expression of Secreted frizzled-related proteins 2 (SFRP2) and
      diminish DNA methyltransferase 1(DNMT1) expression. We also identified that the
      effect of DNMT1 inhibition was completely similar to the effects of HDND-11 on
      SFRP2 gene expression. Furthermore, our results indicated that treatment with
      HDND-11 could suppress activation of Wnt pathway. Taken together, we found that
      the HDND-11diminished inhibitory effect of DNMT1 on SFRP2, thereby down-regulated
      beta-catenin expression and inhibited the activation of Wnt signaling pathways to
      inhibit FLS growth.

PMID- 27720922
TI  - Interaction between G Protein-Coupled Receptor 143 and Tyrosinase: Implications
      for Understanding Ocular Albinism Type 1.
AB  - Developmental eye defects in X-linked ocular albinism type 1 are caused by G
      protein coupled receptor 143 (GPR143) mutations. Mutations result in
      dysfunctional melanosome biogenesis and macromelanosome formation in pigment
      cells, including melanocytes and retinal pigment epithelium. GPR143, primarily
      expressed in pigment cells, localizes exclusively to endolysosomal and
      melanosomal membranes unlike most G protein-coupled receptors, which localize to
      the plasma membrane. There is some debate regarding GPR143 function and
      elucidating the role of this receptor may be instrumental for understanding
      neurogenesis during eye development and for devising therapies for ocular
      albinism type I. Many G protein-coupled receptors require association with other
      proteins to function. These G protein-coupled receptor-interacting proteins also
      facilitate fine-tuning of receptor activity and tissue specificity. We therefore
      investigated potential GPR143 interaction partners, with a focus on the
      melanogenic enzyme tyrosinase. GPR143 coimmunoprecipitated with tyrosinase, while
      confocal microscopy demonstrated colocalization of the proteins. Furthermore,
      tyrosinase localized to the plasma membrane when coexpressed with a GPR143
      trafficking mutant. The physical interaction between the proteins was confirmed
      using fluorescence resonance energy transfer. This interaction may be required in
      order for GPR143 to function as a monitor of melanosome maturation. Identifying
      tyrosinase as a potential GPR143 binding protein opens new avenues for
      investigating the mechanisms that regulate pigmentation and neurogenesis.

PMID- 27720923
TI  - Sperm-less males modulate female behaviour in Ceratitis capitata (Diptera:
      Tephritidae).
AB  - In the Mediterranean fruit fly, Ceratitis capitata (Wiedemann)(Diptera:
      Tephritidae), mating has a strong impact on female biology, leading to a decrease
      in sexual receptivity and increased oviposition and fecundity. Previous studies
      suggest that sperm transfer may play a role in inducing these behavioural
      changes. Here we report the identification of a medfly innexin gene, Cc-inx5,
      whose expression is limited to the germ-line of both sexes. Through RNA
      interference of this gene, we generated males without testes and, consequently,
      sperm, but apparently retaining all the other reproductive organs intact. These
      sperm-less males were able to mate and, like their wild-type counterparts, to
      induce in their partners increased oviposition rates and refractoriness to
      remating. Interestingly, matings to sperm-less males results in oviposition rates
      higher than those induced by copulation with control males. In addition, the
      observed female post-mating behavioural changes were congruent with changes in
      transcript abundance of genes known to be regulated by mating in this species.
      Our results suggest that sperm transfer is not necessary to reduce female sexual
      receptivity and to increase oviposition and fecundity. These data pave the way to
      a better understanding of the role/s of seminal components in modulating female
      post-mating responses. In the long term, this knowledge will be the basis for the
      development of novel approaches for the manipulation of female fertility, and,
      consequently, innovative tools to be applied to medfly control strategies in the
      field.

PMID- 27720924
TI  - Five new lactone derivatives from the stems of Dendrobium nobile.
AB  - Five new lactone derivatives decumbic acids A and B (1 and 2), (-)-decumbic acid
      (3a), (-)- and (+)-dendrolactone (4a and 4b) together with four known compounds
      (3b and 5-7) were isolated from the stems of Dendrobium nobile. Their structures
      were elucidated using comprehensive spectroscopic methods. Compounds 3a and 3b,
      4a and 4b were isolated as two pair of enantiomers by chiral HPLC. The absolute
      configurations of 1, 2, 3a, 4a and 4b were determined by optical rotation and X
      ray crystallographic analysis. The inhibitory activities of all compounds against
      nine phytopathogenic fungi and three cancer cell lines were evaluated.

PMID- 27720925
TI  - Broadening the antibacterial spectrum of histidine kinase autophosphorylation
      inhibitors via the use of epsilon-poly-L-lysine capped mesoporous silica-based
      nanoparticles.
AB  - Two-component systems (TCS) regulate diverse processes such as virulence, stress
      responses, metabolism and antibiotic resistance in bacteria but are absent in
      humans, making them promising targets for novel antibacterials. By incorporating
      recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs)
      into epsilon-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram
      negative (Gr-) permeability barrier for the HKAIs. The observed bactericidal
      activity against Gr- bacteria was shown to be due to the enhanced delivery and
      internalization of the HKAIs and not an inhibitory or synergistic effect of the
      NPs. The NPs had no adverse effects on mammalian cell viability or the immune
      function of macrophages in vitro and showed no signs of toxicity to zebrafish
      larvae in vivo. These results show that HKAIs are promising antibacterials for
      both Gr- and Gr+pathogens and that NPs are a safe drug delivery technology that
      can enhance the selectivity and efficacy of HKAIs against bacteria.

PMID- 27720926
TI  - Profiling the relationship between tumor-associated macrophages and
      pharmacokinetics of liposomal agents in preclinical murine models.
AB  - The mononuclear phagocyte system (MPS) has previously been shown to significantly
      affect the clearance, tumor delivery, and efficacy of nanoparticles (NPs). This
      study profiled MPS cell infiltration in murine preclinical tumor models and
      evaluated how these differences may affect tumor disposition of PEGylated
      liposomal doxorubicin (PLD) in models sensitive and resistant to PLD. Significant
      differences in MPS presence existed between tumor types (e.g. ovarian versus
      endometrial), cell lines within the same tumor type, and location of tumor
      implantation (i.e. flank versus orthotopic xenografts). Further, the differences
      in MPS presence of SKOV-3 ovarian and HEC1A endometrial orthotopic cancer models
      may account for the 2.6-fold greater PLD tumor exposure in SKOV-3, despite
      similar plasma, liver and spleen exposures. These findings suggest that profiling
      the presence of MPS cells within and between tumor types is important in tumor
      model selection and in tumor types and patients likely to respond to NP
      treatment.

PMID- 27720927
TI  - Facile and phase-defined determination of HLA alleles with morpholino
      functionalized nanoparticle probes.
AB  - A number of human leukocyte antigen (HLA) gene alleles have been found to be
      genetic risk markers for immunologically mediated drug hypersensitivity. Clinical
      adoption of HLA pharmacogenomics requires facile and accurate allele screening
      assays. As HLA genes are highly polymorphic, currently available methods are
      usually labor-intensive and liable to generate false positives. Herein we report
      a general strategy for screening HLA alleles with nanoparticle probes. Specific
      HLA alleles can be identified by gauging three to five sequence variants. Single
      polymerase chain reaction (PCR) and dual-PCR methods have been proposed to
      achieve phase-defined determination of the sequence variants. Morpholino
      functionalized gold nanoparticle probes allow for colorimetric and highly
      specific detection. Assays for HLA-B*58:01 and HLA-B*15:02 have been developed
      and validated with 49 selected human genomic DNA samples. The facile nanoparticle
      probe-based assays can be implemented easily in molecular diagnostic laboratories
      for accurate and cost-effective screening of HLA alleles.

PMID- 27720928
TI  - In vivo tumor targeting and biodistribution evaluation of paramagnetic solid
      lipid nanoparticles for magnetic resonance imaging.
AB  - The current study was performed to evaluate the in vivo efficiency of a new nano
      sized contrast agent called paramagnetic Solid Lipid Nanoparticles, pSLNs, having
      promising relaxivity properties for Magnetic Resonance Imaging application. Good
      stability and stealth properties toward macrophage uptake have been demonstrated.
      An in vivo MRI study resulted in an improved signal enhancement in the tumor
      tissue particularly when folate as targeting ligand was used to decorate the
      nanoparticles surface. Afterward, the biodistribution of pSLNs in several organs
      was investigated. The accumulation of pSLNs in kidneys, femoral bones, spleen and
      brain was quite low while high tropism of pSLNs was found for the liver. In this
      regard, approaches to improve the rate of the hepatic clearance have been
      proposed.

PMID- 27720929
TI  - Bio-based polyurethane for tissue engineering applications: How hydroxyapatite
      nanoparticles influence the structure, thermal and biological behavior of
      polyurethane composites.
AB  - In this work, thermoset polyurethane composites were prepared by the addition of
      hydroxyapatite nanoparticles using the reactants polyol polyether and an
      aliphatic diisocyanate. The polyol employed in this study was extracted from the
      Euterpe oleracea Mart. seeds from the Amazon Region of Brazil. The influence of
      hydroxyapatite nanoparticles on the structure and morphology of the composites
      was studied using scanning electron microscopy (SEM) and energy dispersive
      spectroscopy (EDS), the structure was evaluated by Fourier transform infrared
      spectroscopy (FT-IR), thermal properties were analyzed by thermogravimetry
      analysis (TGA), and biological properties were studied by in vitro and in vivo
      studies. It was found that the addition of HA nanoparticles promoted fibroblast
      adhesion while in vivo investigations with histology confirmed that the
      composites promoted connective tissue adherence and did not induce inflammation.
      In this manner, this study supports the further investigation of bio-based,
      polyurethane/hydroxyapatite composites as biocompatible scaffolds for numerous
      tissue engineering applications.

PMID- 27720930
TI  - Adaptation of targeted nanocarriers to changing requirements in antimalarial drug
      delivery.
AB  - The adaptation of existing antimalarial nanocarriers to new Plasmodium stages,
      drugs, targeting molecules, or encapsulating structures is a strategy that can
      provide new nanotechnology-based, cost-efficient therapies against malaria. We
      have explored the modification of different liposome prototypes that had been
      developed in our group for the targeted delivery of antimalarial drugs to
      Plasmodium-infected red blood cells (pRBCs). These new models include: (i)
      immunoliposome-mediated release of new lipid-based antimalarials; (ii) liposomes
      targeted to pRBCs with covalently linked heparin to reduce anticoagulation risks;
      (iii) adaptation of heparin to pRBC targeting of chitosan nanoparticles; (iv) use
      of heparin for the targeting of Plasmodium stages in the mosquito vector; and (v)
      use of the non-anticoagulant glycosaminoglycan chondroitin 4-sulfate as a heparin
      surrogate for pRBC targeting. The results presented indicate that the tuning of
      existing nanovessels to new malaria-related targets is a valid low-cost
      alternative to the de novo development of targeted nanosystems.

PMID- 27720931
TI  - CysLT1R downregulation reverses intracerebroventricular streptozotocin-induced
      memory impairment via modulation of neuroinflammation in mice.
AB  - Our previous studies showed that cysteinyl leukotrienes receptor 1 (CysLT1R) is
      upregulated in amyloid-beta (Abeta)-induced neurotoxicity and that administration
      of CysLT1R antagonists such as pranlukast or montelukast can ameliorate memory
      impairment in mice. In the current study, we sought to explore the role of
      CysLT1R in intracerebroventricular streptozotocin (STZ-ICV)-induced mouse model
      of memory impairment and neuroinflammation through shRNA-mediated knockdown of
      CysLT1R and also its pharmacological blockade by pranlukast. ICR mice were
      infused with STZ (3.0mg/kg) by a single bilateral stereotaxic ICV microinjection
      followed by administration of CysLT1R-shRNA (intra-hippocampal) or pranlukast
      (intragastric, IG). After 21days, a set of behavioral and biochemical tests were
      performed in order to assess the degree of memory impairment and
      neuroinflammation in mice. STZ-infused mice spent less time in the target
      quadrant of Morris water maze test and took more time to find the shock-free arm
      in modified Y-maze test, which were rescued in the CysLT1R-knockdowned or
      pranlukast-treated mice. STZ-induced memory impairment was also accompanied by an
      elevated level of hippocampal CysLT1R, microglial activation, increased IL-1beta,
      and TNF-alpha. Such elevation of these factors was found to be mediated through
      the classical NF-kappaB pathway and administration of CysLT1R-shRNA or pranlukast
      for 21days reversed all these parameters, suggesting a role of CysLT1R in STZ
      induced memory deficit and neuroinflammation.

PMID- 27720932
TI  - Hydrogen sulfide donors alleviate itch secondary to the activation of type-2
      protease activated receptors (PAR-2) in mice.
AB  - Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule
      and we have previously found that it can inhibit histamine-mediated itching.
      Pruritus is the most common symptom of cutaneous diseases and anti-histamines are
      the usual treatment; however, anti-histamine-resistant pruritus is common in some
      clinical settings. In this way, the involvement of mediators other than histamine
      in the context of pruritus requires new therapeutic targets. Considering that the
      activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus
      both in rodents and humans, in this study we investigated the effect of H2S
      donors on the acute scratching behavior mediated by PAR-2 activation in mice, as
      well as some of the possible pharmacological mechanisms involved. The intradermal
      injection of the PAR-2 peptide agonist SLIGRL-NH2 (8-80nmol) caused a dose
      dependent scratching that was unaffected by intraperitoneal pre-treatment with
      the histamine H1 antagonist pyrilamine (30mg/kg). Co-injection of SLIGRL-NH2
      (40nmol) with either the slow-release H2S donor GYY4137 (1 and 3nmol) or the
      spontaneous donor NaHS (1 and 0.3nmol) significantly reduced pruritus. Co
      treatment with the KATP channel blocker glibenclamide (200nmol) or the nitric
      oxide (NO) donor sodium nitroprusside (10nmol) abolished the antipruritic effects
      of NaHS; however, the specific soluble guanylyl cyclase inhibitor ODQ (30MUg) had
      no significant effects. The transient receptor potential ankyrin type 1 (TRPA1)
      antagonist HC-030031 (20MUg) significantly reduced SLIGRL-NH2-induced pruritus;
      however pruritus induced by the TRPA1 agonist AITC (1000nmol) was unaffected by
      NaHS. Based on these data, we conclude that pruritus secondary to PAR-2
      activation can be reduced by H2S, which acts through KATP channel opening and
      involves NO in a cyclic guanosine monophosphate (cGMP)-independent manner.
      Furthermore, TRPA1 receptors mediate the pruritus induced by activation of PAR-2,
      but H2S does not interfere with this pathway. These results provide additional
      support for the development of new therapeutical alternatives, mainly intended
      for treatment of pruritus in patients unresponsive to anti-histamines.

PMID- 27720933
TI  - Activation of the pro-migratory bone morphogenetic protein receptor 1B gene in
      human MDA-MB-468 triple-negative breast cancer cells that over-express CYP2J2.
AB  - Secondary metastases are the leading cause of mortality in patients with breast
      cancer. Cytochrome P450 (CYP) 2J2 (CYP2J2) is upregulated in many human tumors
      and generates epoxyeicosanoids from arachidonic acid that promote tumorigenesis
      and metastasis, but at present there is little information on the genes that
      mediate these actions. In this study MDA-MB-468 breast cancer cells were stably
      transfected with CYP2J2 (MDA-2J2 cells) and Affymetrix microarray profiling was
      undertaken. We identified 182 genes that were differentially expressed in MDA-2J2
      cells relative to control (MDA-CTL) cells (log[fold of control] >=2). From gene
      ontology pathway analysis bone morphogenetic protein (BMP) receptor 1B (BMPR1B)
      emerged as an important upregulated gene in MDA-2J2 cells. Addition of the BMPR1B
      ligand BMP2 stimulated the migration of MDA-2J2 cells, but not MDA-CTL cells,
      from 3D-matrigel droplets. Migration of MDA-2J2 cells was prevented by the BMPR
      antagonist dorsomorphin. These findings indicate that over-expression of CYP2J2
      in MDA-MB-468-derived breast cancer cells activates BMPR1B expression that may
      contribute to increased migration. Targeting BMPR1B may be a novel approach to
      inhibit the metastatic activity of breast cancers that contain high levels of
      CYP2J2.

PMID- 27720934
TI  - In-vivo organ engineering: Perfusion of hepatocytes in a single liver lobe
      scaffold of living rats.
AB  - Organ decellularization is emerging as a promising regenerative medicine approach
      as it is able to provide an acellular, three-dimensional biological scaffold
      material that can be seeded with living cells for organ reengineering. However
      this application is currently limited to donor-derived decellularized organs for
      reengineering in vitro and no study has been conducted for re-engineering the
      decellularized organ in vivo. We developed a novel technique of a single liver
      lobe decellularization in vivo in live animals. Using a surgical method to
      generate a by-pass circulation through the portal vein and infra-hepatic vena
      cava with a perfusion chamber system, we decellularized the single liver lobe and
      recellularized it with allogenic primary hepatocytes. Our results showed that the
      decellularization process in vivo can preserve the vascular structural network
      and functional characteristics of the native liver lobe. It allows for efficient
      recellularization of the decellularized liver lobe matrix with allogenic primary
      hepatocytes. Upon the re-establishment of blood circulation, the recellularized
      liver lobe is able to gain the function and the allogenic hepatocytes are able to
      secret albumin. Our findings provide a proof of principle for the in vivo
      reengineering of liver.

PMID- 27720935
TI  - Systemic inflammatory profiles and their relationships with demographic,
      behavioural and clinical features in acute low back pain.
AB  - Systemic inflammation is linked with development and persistence of many
      pathological pain states. Although chronic phase inflammatory responses are well
      reported, the acute phase has received limited attention. Here we investigated
      circulating pro-inflammatory cytokines and C-reactive protein (CRP), and explored
      their relationships with symptom severity and other factors in acute low back
      pain (LBP). Ninety-nine individuals within two weeks of onset of acute LBP and 55
      pain-free controls completed questionnaires related to their pain (visual
      analogue scale, VAS) and disability, behaviour, sleep quality and psychological
      status. CRP, interleukin-6 (IL-6), tumor necrosis factor (TNF) and interleukin
      1beta (IL-1beta) were measured from serum samples. Biomarkers were compared
      between LBP and control participants, and in a separate analysis, for those with
      "high-pain" (VAS ?4) and "low-pain" (VAS <4). The relationships between
      biomarkers and all other variables, including other cytokines/CRP were assessed.
      CRP was higher in LBP than controls and in those with high- than low-pain
      (p<0.01). IL-6 was higher in those with high- than low-pain (p<0.05), but not
      controls. Various pain and non-pain factors were associated with each biomarker
      differently. These findings suggest systemic CRP and IL-6 are important
      contributors to inflammation in the early post-onset phase of LBP and that
      various factors can shape these responses.

PMID- 27720936
TI  - MiR-17-92 represses PTPROt and PP2A phosphatases and amplifies tonic BCR
      signaling in DLBCL cells.
AB  - B-cell receptor (BCR) signaling plays a pivotal role in the pathogenesis of
      diffuse large B-cell lymphoma (DLBCL) and targeting the BCR pathway is a highly
      promising therapeutic strategy in this malignancy. The oncogenic microRNA miR-17
      92 modulates multiple cellular processes such as survival, proliferation,
      apoptosis, angiogenesis, and BCR signaling. In the present study, we identified
      new targets of miR-17-92, PTPROt (protein phosphatase, receptor type O,
      truncated) and PP2A (protein phosphatase 2A) phosphatases, which regulate the
      activity of spleen tyrosine kinase (SYK) and AKT, critical components of BCR
      signal transduction in DLBCL cells. Introduction of miR-17-92 into DLBCL cells
      dampened the expression of the PTPROt and PP2A regulatory subunits PPP2R2A
      (protein phosphatase 2, regulatory subunit B, alpha) and PPP2R5E (protein
      phosphatase 2, regulatory subunit B, epsilon isoform) and increased the magnitude
      of SYK and AKT phosphorylation upon BCR ligation. Finally, we found that miR-17
      92 expression modulates response to inhibitors of BCR signaling because
      downregulation of miR-17-92 increased SYK inhibitor-mediated toxicity in DLBCL
      cells. Our study reveals novel posttranscriptional regulatory pathways that
      contribute to the deregulation of BCR signaling and modulate SYK inhibitor
      activity in DLBCL.

PMID- 27720937
TI  - Using zebrafish models of leukemia to streamline drug screening and discovery.
AB  - Current treatment strategies for acute leukemias largely rely on nonspecific
      cytotoxic drugs that result in high therapy-related morbidity and mortality. Cost
      effective, pertinent animal models are needed to link in vitro studies with the
      development of new therapeutic agents in clinical trials on a high-throughput
      scale. However, targeted therapies have had limited success moving from bench to
      clinic, often due to unexpected off-target effects. The zebrafish has emerged as
      a reliable in vivo tool for modeling human leukemia. Zebrafish genetic and
      xenograft models of acute leukemia provide an unprecedented opportunity to
      conduct rapid, phenotype-based screens. This allows for the identification of
      relevant therapies while simultaneously evaluating drug toxicity, thus
      circumventing the limitations of target-centric approaches.

PMID- 27720938
TI  - Identification of gene expression profiling associated with erlotinib-related
      skin toxicity in pancreatic adenocarcinoma patients.
AB  - Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
      that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's
      most frequently reported side effect as a result of EGFR inhibition is skin rash
      (SR), a symptom which has been associated with a better therapeutic response to
      the drug. Gene expression profiling can be used as a tool to predict which
      patients will develop this important cutaneous manifestation. The aim of the
      present study was to identify which genes may influence the appearance of SR in
      PDAC patients. The study included 34 PDAC patients treated with erlotinib: 21
      patients developed any grade of SR, while 13 patients did not (controls). Before
      administering any chemotherapy regimen and the development of SR, we collected
      RNA from peripheral blood samples of all patients and studied the differential
      gene expression pattern using the Illumina microarray platform HumanHT-12 v4
      Expression BeadChip. Seven genes (FAM46C, IFITM3, GMPR, DENND6B, SELENBP1, NOL10,
      and SIAH2), involved in different pathways including regulatory, migratory, and
      signalling processes, were downregulated in PDAC patients with SR. Our results
      suggest the existence of a gene expression profiling significantly correlated
      with erlotinib-induced SR in PDAC that could be used as prognostic indicator in
      this patients.

PMID- 27720939
TI  - Differential expression of microRNAs from miR-17 family in the cerebellum of
      mucopolysaccharidosis type I mice.
AB  - Mucopolysaccharidosis type I (MPS I) is caused by deficiency of alpha-l
      iduronidase, involved in degradation of glycosaminoglycans. Clinical
      manifestations are widely variable and patients with severe phenotype present
      developmental delay and cognitive decline, among other systemic alterations. MPS
      I patients present secondary accumulation of gangliosides in neuronal cells,
      besides accumulation of undegraded glycosaminoglycans. Reduction of Neu1
      expression has been previously observed in the cerebellum of MPS I mice; to be
      active, neuraminidase 1 forms the lysosomal multienzyme complex (LMC) with two
      other proteins, beta-galactosidase and protective protein/cathepsin A, involved
      in stepwise degradation of gangliosides in the lysosomes. In this study, we
      evaluated relative expression of LMC genes and six possible regulators of their
      expression, microRNAs (miRNAs) from miR-17 family, which are predicted to target
      at least two LMC components, in the cerebellum of MPS I mice by real-time PCR.
      Neu1 was significantly underexpressed in MPS I mice cerebellum, whereas
      expression of other LMC genes was similar to controls. miR-20b and miR-106b were
      differentially expressed in MPS I mice, suggesting that they may be involved in
      the reduction of Neu1 expression; miR-20b-5p was overexpressed while miR-20b-3p
      and miR-106b-5p were underexpressed. The ratio between miR-20b-3p and miR-20b-5p
      was also altered in cerebellum of MPS I mice. Confirmation of binding predictions
      and analysis of the direct role of these miRNAs in the regulation of Neu1
      expression could bring important information regarding LMC function. Since miRNAs
      from miR-17 family are involved in regulation of diverse biological processes,
      our results also point to new pathogenic cascades to be investigated in MPS I.

PMID- 27720940
TI  - Differentially expressed mitochondrial genes in breast cancer cells: Potential
      new targets for anti-cancer therapies.
AB  - It has been reported that tumor growth and proliferation correspond to
      mitochondrial dysfunction and that the tumor cellular microenvironment plays a
      key role in tumor progression, representing an area that might be manipulated to
      confer therapeutic anti-tumor benefits. In this article, we have identified
      mitochondrial genes, largely nuclear-encoded genes, which are differentially
      expressed in breast cancer epithelial and stromal cells compared to cells from
      normal breast tissues. We determined that gene expression of the mitochondrial
      membrane respiratory chain complex I and IV and ATP synthesis were reduced in
      both in epithelial and stromal cancer cells compared to normal breast cells. We
      also found transport-related genes were significantly more highly expressed in
      breast cancer epithelial cells. Our data also suggest that mitochondria are
      likely to proliferate in breast cancer stromal cells, which is supported by the
      observation that MRPL12, POLG, and RNASEH1 are all up-regulated in cancerous
      stromal cells. In addition, we present an improved simulated annealing algorithm,
      SANetWalker, which can be used to detect the functional module. At the same time,
      this method has a minimal effect on network topology and can be used to identify
      the highest confidence functional module. Using SANetWalker, we obtained the
      highest confidence (90%) functional module with a fumarate hydratase (FH)
      centered network with 40 nodes and 107 edges. Functional analysis revealed that
      glutamine metabolism genes were significantly up-regulated in both epithelial and
      stromal cells from breast cancer tissues, which implicates glutamine metabolism
      in breast cancer growth and metastasis.

PMID- 27720941
TI  - The synergistic effect of photodynamic therapy and photothermal therapy in the
      presence of gold-gold sulfide nanoshells conjugated Indocyanine green on HeLa
      cells.
AB  - BACKGROUND: Photodynamic therapy (PDT) and photothermal therapy (PTT) are two
      known optical remedies of cancer. PTT can be combined with other therapies. One
      of the limitations of optical therapies is the penetration of light into
      biological tissues, which reduces its effectiveness due to usage of
      photosensitizers and PTT agents, which are absorbed in the NIR region that
      provides the maximum penetration. For instance, Indocyanine green (ICG) serves as
      a photosensitizer and Gold nanostructures as agents for PTT. GGS is a gold
      nanoshell with two absorption peaks in the NIR and visible regions. The aim of
      this study is to evaluate the synergistic effect of PDT and PTT in the presence
      of GGS conjugated with ICG. METHODS: After synthesizing GGS, ICG was conjugated
      with GGS. The specifications and cytotoxicity of agents were identified. Cells
      were irradiated by an 808nm laser with or without the agents and three laser
      outputs were achieved, with each having four different exposure times. The
      viability of treated cells was determined via MTT assay. RESULT: The irradiation
      of the laser did not produce any significant effect by itself or in the presence
      of GGS. The maximum cell death recorded for GGS, ICG and GGS-ICG were 15+/-7%,
      50+/-3% and 31+/-3% respectively. ICG and GGS-ICG differs significantly for
      exposures higher than 2250J/cm2. CONCLUSION: The conjugate was provided through a
      simple process and a greater chemical stability compared to GGS was achieved.
      Moreover, it induced a stronger photodynamic and photothermal effect on the
      cells. This is a promising result which can help enhance the effectiveness of a
      minimally invasive treatment.

PMID- 27720942
TI  - Treatment of unresectable extrahepatic cholangiocarcinoma using hematoporphyrin
      photodynamic therapy: A prospective study.
AB  - BACKGROUND: The available evidence of Photodynamic therapy (PDT) combined with
      stent placement treatment for unresectable extrahepatic cholangiocarcinoma (EHCC)
      is still insufficient. It also remains unclear whether PDT influences systemic
      inflammatory response. AIM: To explore the clinical efficacy and safety of the
      combination treatment and the systemic inflammatory response in patients with
      EHCC. METHODS: Patients with unresectable EHCC underwent either the combined
      treatment using Hematoporphyrin PDT and stent placement (PDT+stent group, n=12)
      or stent-only (stent group, n=27). The primary end-point was overall survival.
      Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels were measured.
      Quality of life was assessed using the Karnofsky performance scale (KPS) every 3
      months. RESULTS: Average survival time (13.8 vs. 9.6 months), and 6-month (91.7%
      vs. 74.1%), and 1-year (58.3% vs. 3.7%) survival rates of PDT+stent group were
      significantly increased compared with the stent group. KPS scores in the
      PDT+stent group were significantly improved. TNF-alpha and IL-6 levels were
      significantly increased in the PDT+stent group. CONCLUSION: Hematoporphyrin-PDT
      combined with stent placement is an effective and safe treatment for EHCC. The
      treatment might promote systemic inflammatory response.

PMID- 27720944
TI  - Molecular epidemiology of coxsackievirus A16 strains from four sentinel
      surveillance sites in Peru.
AB  - OBJECTIVES: To determine the molecular epidemiology of seven coxsackievirus A16
      (CVA16) strains previously reported by this research group. METHODS: Full-length
      VP1 and VP4 sequences were obtained and phylogenetic analyses were performed.
      RESULTS: Six strains were classified as genotype C. Moreover, one divergent
      strain not clustered in any of the three currently reported genotypes was found.
      CONCLUSION: This is the first report of CVA16 in Peru and provides valuable
      baseline data about its potential distribution in South America, as well as
      evidence of a potential divergent genotype that has never before been reported.

PMID- 27720945
TI  - Evaluation of the rapid influenza detection tests GOLD SIGN FLU and Quick Navi
      Flu for the detection of influenza A and B virus antigens in adults during the
      influenza season.
AB  - As the characteristics and accuracy of rapid influenza detection tests (RIDTs)
      vary, the development of a high-performance RIDT has been eagerly anticipated. In
      this study, the new RIDT GOLD SIGN FLU and the existing RIDT Quick Navi-Flu were
      evaluated in terms of detecting the antigens of influenza viruses A and B in
      Japanese adults with influenza-like symptoms. The study was performed from
      December 2013 to March 2014. Among the 123 patients from whom nasopharyngeal swab
      specimens were collected, 59 tested positive by viral isolation as the gold
      standard method (influenza A, n=38; influenza B, n=21). For GOLD SIGN FLU, the
      sensitivities were 73.7% and 81.0%, and the specificities were 97.6% and 98.0%
      for influenza A and B, respectively. For Quick Navi-Flu, the sensitivities were
      86.8% and 85.7%, and the specificities were 98.8% and 100% for influenza A and B,
      respectively. The time to the appearance of the line on the test strip was less
      than 3min for influenza A and less than 2min for influenza B with both RIDTs in
      more than 90% of cases. GOLD SIGN FLU was useful for diagnosing influenza A, and
      the result was readily available for influenza B particularly among adult
      patients. Quick Navi-Flu showed better sensitivities and specificities than GOLD
      SIGN FLU.

PMID- 27720943
TI  - The V-motifs facilitate the substrate capturing step of the PTS elevator
      mechanism.
AB  - We propose that the alternative crystal forms of outward open UlaA (which are
      experimental, not simulated, and contain the substrate in the cavity) can be used
      to interpret/validate the MD results from MalT (the substrate capture step, which
      involves the mobile second TMSs of the V-motifs, TMSs 2 and 7). Since the crystal
      contacts are the same between the two alternative crystal forms of outward open
      UlaA, the striking biological differences noted, including rearranged hydrogen
      bonds and salt bridge coordination, are not attributable to crystal packing
      differences. Using transport assays, we identified G58 and G286 as essential for
      normal vitamin C transport, but the comparison of alternative crystal forms
      revealed that these residues to unhinge TMS movements from substrate-binding side
      chains, rendering the mid-TMS regions of homologous TMSs 2 and 7 relatively
      immobile. While the TMS that is involved in substrate binding in MalT is part of
      the homologous bundle that holds the two separate halves of the transport
      assembly (two proteins) together, an unequal effect of the two knockouts was
      observed for UlaA where both V-motifs are free from such dimer interface
      interactions.

PMID- 27720946
TI  - 6-(3,4-Dihydro-1H-isoquinoline-2-yl)-N-(6-methoxypyridine-2-yl) nicotinamide-26
      (DIMN-26) decreases cell proliferation by induction of apoptosis and
      downregulation of androgen receptor signaling in human prostate cancer cells.
AB  - Previously, we reported that 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6
      methylpyridin-2-yl) nicotinamide (DIMN) analogues inhibited the growth of
      prostate cancer cells as an anti-androgenic compound. In the present study, we
      evaluated cytotoxic effects of these DIMN derivatives and found that DIMN-26 most
      potently inhibited the proliferation of the LNCap-LN3 androgen-dependent and
      DU145 androgen-independent prostate cancer cells through induction of G2/M phase
      cell cycle arrest and subsequent apoptosis. The G2/M phase arrest was found due
      to increases in the activation of cdc2 (also known as cyclin-dependent kinase 1,
      CDK1)/cyclin B1 complex. DIMN-26 also induced apoptosis in LNCap-LN3 and DU145
      prostate cancer cells through activation of caspase-3, -8, and -9, and cleavage
      of poly(ADP-ribose) polymerase-1 (PARP-1). In addition, DIMN-26 caused the
      dephosphorylation and mitochondrial accumulation of Bad protein and induced the
      loss of mitochondria membrane potential, consequently releasing cytochrome c into
      the cytosol of the cell. Furthermore, overexpression of AKT protein significantly
      reduced DIMN-26-induced PARP-1 cleavage and p-Bad decrease and cdc2 activation.
      In addition, DIMN-26 inhibited the 5alpha-dihydrotestosterone (DHT)-induced cell
      growth and proliferation and nuclear translocation and transcriptional activities
      of androgen receptor (AR) in LNCap-LN3 prostate cancer cells. Consistent with
      these findings, DIMN-26 significantly inhibited the DHT-induced expression of AR
      response genes (ARGs), such as prostate-specific antigen (PSA), AR, beta2
      microglobulin (B2M), selenoprotein P (SEPP1), and ste20-related proline-alanine
      rich kinase (SPAK) in LNCap-LN3 prostate cancer cells. Taken together, these
      results suggest that DIMN-26 plays a therapeutic role not only in induction of
      G2/M arrest and apoptosis but also in suppression of androgen receptor signaling
      in androgen-dependent and androgen-independent prostate cancer cells.

PMID- 27720947
TI  - The plant-derived triterpenoid tingenin B is a potent anticancer agent due to its
      cytotoxic activity on cancer stem cells of breast cancer in vitro.
AB  - Despite the rapid advances in chemotherapy regimens, the outcome of patients with
      breast cancer is not satisfactory. One of the reasons of this dissatisfaction is
      that subsets of cells in tumors which referred as cancer stem cells (CSCs) show
      and/or gain resistance to therapies. Thus, compounds that target CSCs are
      urgently needed. Since some are already used in the clinic, natural products have
      great potential for further development as anti cancer drugs. The aim of this
      study is to investigate the cytotoxic activity of tingenin b (or 22beta
      hydroxytingenone) which is a quinone-methide triterpenoid structurally related to
      tingenone, against breast CSCs (stem-cell enriched population from MCF-7 cell
      line, MCF-7s). It has been found that tingenin b was cytotoxic against MCF-7s
      (IC50 value for 48 h was found to be 2.38 MUM) by inducing apoptosis. It was
      evident by Annexin V staining positivity, decreased mitochondrial membrane
      potential and Bcl-2 dephosphorylation with a concomitant increase in Bax protein
      expression. In addition, endoplasmic reticulum stress was also found to be
      involved in tingenin b-induced cell death. In conclusion, the results warrant
      further studies aimed at elucidating and corroborating its possible use in the
      treatment of breast cancer.

PMID- 27720948
TI  - Functional changes in brain activity after hypnosis in patients with dental
      phobia.
AB  - Visiting the dentist is often accompanied by apprehension or anxiety. People, who
      suffer from specific dental phobia (a disproportional fear of dental) procedures
      show psychological and physiological symptoms which make dental treatments
      difficult or impossible. For such purposes, hypnosis is often used in dental
      practice as an alternative for a number of treatments adjuvant or instead of
      sedation or general anaesthetics, as medication is often associated with risks
      and side effects. This is the first study to address the effects of a brief
      dental hypnosis on the fear processing structures of the brain in dental phobics
      using functional magnetic resonance imaging (fMRI). 12 dental phobics (DP; mean
      34.9years) and 12 healthy controls (CO; mean 33.2years) were scanned with a 3T
      MRI whole body-scanner observing brain activity changes after a brief hypnotic
      invervention. An fMRI event-related design symptom provocation task applying
      animated audio-visual pseudorandomized strong phobic stimuli was presented in
      order to maximize the fearful reactions during scanning. Control videos showed
      the use of familiar electronic household equipment. In DP group, main effects of
      fear condition were found in the left amygdala and bilaterally in the anterior
      cingulate cortex (ACC), insula and hippocampu (R<L). During hypnosis DP showed a
      significantly reduced activation in all of these areas. Reduced neural activity
      patterns were also found in the control group. No amygdala activation was
      detected in healthy subjects in the two experimental conditions. Compared to DP,
      CO showed less bilateral activation in the insula and ACC in the awake condition.
      Findings show that anxiety-provoking stimuli such as undergoing dental surgery,
      endodontic treatments or insufficient anaesthetics, can be effectively reduced
      under hypnosis. The present study gives scientific evidence that hypnosis is a
      powerful and successful method for inhibiting the reaction of the fear circuitry
      structures.

PMID- 27720949
TI  - Learning and retrieving holistic and componential visual-verbal associations in
      reading and object naming.
AB  - Understanding the neural processes that underlie learning to read can provide a
      scientific foundation for literacy education but studying these processes in real
      world contexts remains challenging. We present behavioural data from adult
      participants learning to read artificial words and name artificial objects over
      two days. Learning profiles and generalisation confirmed that componential
      learning of visual-verbal associations distinguishes reading from object naming.
      Functional MRI data collected on the second day allowed us to identify the neural
      systems that support componential reading as distinct from systems supporting
      holistic visual-verbal associations in object naming. Results showed increased
      activation in posterior ventral occipitotemporal (vOT), parietal, and frontal
      cortices when reading an artificial orthography compared to naming artificial
      objects, and the reverse profile in anterior vOT regions. However, activation
      differences between trained and untrained words were absent, suggesting a lack of
      cortical representations for whole words. Despite this, hippocampal responses
      provided some evidence for overnight consolidation of both words and objects
      learned on day 1. The comparison between neural activity for artificial words and
      objects showed extensive overlap with systems differentially engaged for real
      object naming and English word/pseudoword reading in the same participants. These
      findings therefore provide evidence that artificial learning paradigms offer an
      alternative method for studying the neural systems supporting language and
      literacy. Implications for literacy acquisition are discussed.

PMID- 27720951
TI  - Ligand binding affinity and changes in the lateral diffusion of receptor for
      advanced glycation endproducts (RAGE).
AB  - The effect of ligand on the lateral diffusion of receptor for advanced glycation
      endproducts (RAGE), a receptor involved in numerous pathological conditions,
      remains unknown. Single particle tracking experiments that use quantum dots
      specifically bound to hemagglutinin (HA)-tagged RAGE (HA-RAGE) are reported to
      elucidate the effect of ligand binding on HA-RAGE diffusion in GM07373 cell
      membranes. The ligand used in these studies is methylglyoxal modified-bovine
      serum albumin (MGO-BSA) containing advanced glycation end products modifications.
      The binding affinity between soluble RAGE and MGO-BSA increases by 1.8 to 9.7
      fold as the percent primary amine modification increases from 24 to 74% and with
      increasing negative charge on the MGO-BSA. Ligand incubation affects the HA-RAGE
      diffusion coefficient, the radius of confinement, and duration of confinement.
      There is, however, no correlation between MGO-BSA ligand binding affinity with
      soluble RAGE and the extent of the changes in HA-RAGE lateral diffusion. The
      ligand induced changes to HA-RAGE lateral diffusion do not occur when cholesterol
      is depleted from the cell membrane, indicating the mechanism for ligand-induced
      changes to HA-RAGE diffusion is cholesterol dependent. The results presented here
      serve as a first step in unraveling how ligand influences RAGE lateral diffusion.

PMID- 27720952
TI  - Retinoylation (covalent modification by retinoic acid) of Rho-GDIbeta in the
      human myeloid leukemia cell line HL60 and its functional significance.
AB  - Retinoic acid (RA) has a variety of biological effects in mammalian cells and
      tissues. It is well known that RA induces differentiation of human acute
      promyelocytic leukemia (APL) HL60 cells, fresh human APL cells, and clinical
      remission in patients with APL. Retinoylation (acylation of proteins by RA) is a
      possible pathway for RA action. However, an understanding of the role that
      retinoylation plays in the actions of RA is lacking. In the current study,
      several retinoylated proteins were detected in RA-treated HL60 fractions
      following Mono Q anion exchange chromatography and analysis using two-dimensional
      polyacrylamide gel electrophoresis. One of the retinoylated proteins was
      identified as Rho-GDIbeta (28kDa) by TOF-MS and co-migration with Rho-GDIbeta
      (28kDa). Truncated Rho-GDIbeta (23kDa, N?19), a product of cleavage by caspase-3,
      was not retinoylated. RA covalently bound to the Thr2 residue in Rho-GDIbeta
      (5kDa), which is the second product resulting from the cleavage of Rho-GDIbeta
      (28kDa) by caspase-3. RA treatment increased the level of Rho-GDIbeta (28kDa) and
      decreased the level of Rho-GDIbeta (23kDa). RA did not induce caspase-3 activity
      or Rho-GDIbeta mRNA expression. It is likely that retinoylation of Rho-GDIbeta
      increases its metabolic stability.

PMID- 27720953
TI  - Comparative thoracic anatomy of the wild type and wingless (wg1cn1) mutant of
      Drosophila melanogaster (Diptera).
AB  - Genetically modified organisms are crucial for our understanding of gene
      regulatory networks, physiological processes and ontogeny. With modern molecular
      genetic techniques allowing the rapid generation of different Drosophila
      melanogaster mutants, efficient in-depth morphological investigations become an
      important issue. Anatomical studies can elucidate the role of certain genes in
      developmental processes and point out which parts of gene regulatory networks are
      involved in evolutionary changes of morphological structures. The wingless
      mutation wg1 of D. melanogaster was discovered more than 40 years ago. While
      early studies addressed the external phenotype of these mutants, the
      documentation of the internal organization was largely restricted to the
      prominent indirect flight muscles. We used SEM micrographs, histological serial
      sections, MU-computed tomography, CLSM and 3D reconstructions to study and
      document the thoracic skeletomuscular system of the wild type and mutant. A
      recently introduced nomenclature for the musculature of neopteran insects was
      applied to facilitate comparisons with closely or more distantly related taxa.
      The mutation is phenotypically mainly characterized by the absence of one or both
      wings and halteres. The wing is partly or entirely replaced by duplications of
      mesonotal structures, whereas the haltere and its associated muscles are
      completely absent on body sides showing the reduction. Both the direct and
      indirect mesothoracic flight muscles are affected by loss and reorientation of
      bundles or fibers. Our observations lead to the conclusion that the wingless
      mutation causes a homeotic transformation in the imaginal discs of wings and
      halteres with a direct effect on the development of skeletal structures and an
      indirect effect on the associated muscular system.

PMID- 27720950
TI  - Molecular mechanisms of mechanotransduction in integrin-mediated cell-matrix
      adhesion.
AB  - Cell-matrix adhesion complexes are multi-protein structures linking the
      extracellular matrix (ECM) to the cytoskeleton. They are essential to both cell
      motility and function by bidirectionally sensing and transmitting mechanical and
      biochemical stimulations. Several types of cell-matrix adhesions have been
      identified and they share many key molecular components, such as integrins and
      actin-integrin linkers. Mechanochemical coupling between ECM molecules and the
      actin cytoskeleton has been observed from the single cell to the single molecule
      level and from immune cells to neuronal cells. However, the mechanisms underlying
      force regulation of integrin-mediated mechanotransduction still need to be
      elucidated. In this review article, we focus on integrin-mediated adhesions and
      discuss force regulation of cell-matrix adhesions and key adaptor molecules,
      three different force-dependent behaviors, and molecular mechanisms for
      mechanochemical coupling in force regulation.

PMID- 27720954
TI  - In-vitro investigation regarding the effects of Gelucire(r) 44/14 and Labrasol(r)
      ALF on the secretory intestinal transport of P-gp substrates.
AB  - In this present study, the secretory transport of P-gp substrates, rhodamine 123
      and digoxin, was evaluated using a Caco-2/HT29-MTX co-culture characterized by an
      efflux mechanism and a paracellular permeability closer to the human intestinal
      barrier compared to the Caco-2 monolayer gold standard. The influence of
      simulated intestinal fluids termed FeSSIF and FaSSIF on the intestinal absorption
      was also assessed in comparison with a conventional saline buffer. Labrasol(r)
      ALF and Gelucire(r) 44/14 in saline buffer significantly decreased to 83% and
      62%, the P-gp-mediated transport of rhodamine 123 across the co-culture,
      respectively. The effects of Gelucire(r) 44/14 were much more exacerbated with
      the Caco-2 monolayer model with a reduced permeability to 34% but they were
      partially reversed in the co-culture with FeSSIF. The modulation by the lipid
      excipients of digoxin secretory transport across the Caco-2 monolayer and the co
      culture was reduced compared with the rhodamine 123. This work also emphasizes
      the numerous parameters that have to be considered for predicting accurately the
      effects of potential P-gp inhibitors including the in-vitro model, the incubation
      media and the intrinsic properties of P-gp substrates.

PMID- 27720955
TI  - HIC1 epigenetically represses CIITA transcription in B lymphocytes.
AB  - Differentiation of B lymphocytes into isotope-specific plasma cells represents a
      hallmark event in adaptive immunity. During B cell maturation, expression of the
      class II transactivator (CIITA) gene is down-regulated although the underlying
      epigenetic mechanism is not completely defined. Here we report that
      hypermethylated in cancer 1 (HIC1) was up-regulated in differentiating B
      lymphocytes paralleling CIITA repression. Over-expression of HIC1 directly
      repressed endogenous CIITA transcription in B cells. Reporter assay and chromatin
      immunoprecipitation (ChIP) assay confirmed that HIC1 bound to the proximal CIITA
      type III promoter (-545/-113); mutation of a conserved HIC1 site within this
      region abrogated CIITA trans-repression. More important, depletion of HIC1 with
      small interfering RNA (siRNA) restored CIITA expression in differentiating B
      cells. Mechanistically, HIC1 preferentially interacted with and recruited DNMT1
      and DNMT3b to the CIITA promoter to synergistically repress CIITA transcription.
      On the contrary, silencing of DNMT1/DNMT3b or inhibition of DNMT activity with 5
      aza-dC attenuated CIITA trans-repression. Therefore, our data identify HIC1 as a
      novel factor involved in B cell differentiation acting as an epigenetic repressor
      of CIITA transcription.

PMID- 27720956
TI  - Individual differences shape the content of visual representations.
AB  - Visually perceiving a stimulus activates a pictorial representation of that item
      in the brain, but how pictorial is the representation of a stimulus in the
      absence of visual stimulation? Here I address this question with a review of the
      literatures on visual imagery (VI), visual working memory (VWM), and visual
      preparatory templates, all of which require activating visual information in the
      absence of sensory stimulation. These processes have historically been studied
      separately, but I propose that they can provide complimentary evidence for the
      pictorial nature of their contents. One major challenge in studying the contents
      of visual representations is the discrepant findings concerning the extent of
      overlap (both cortical and behavioral) between externally and internally sourced
      visual representations. I argue that these discrepancies may in large part be due
      to individual differences in VI vividness and precision, the specific
      representative abilities required to perform a task, appropriateness of visual
      preparatory strategies, visual cortex anatomy, and level of expertise with a
      particular object category. Individual differences in visual representative
      abilities greatly impact task performance and may influence the likelihood of
      experiences such as intrusive VI and hallucinations, but research still
      predominantly focuses on uniformities in visual experience across individuals. In
      this paper I review the evidence for the pictorial content of visual
      representations activated for VI, VWM, and preparatory templates, and highlight
      the importance of accounting for various individual differences in conducting
      research on this topic.

PMID- 27720957
TI  - The complete nucleotide sequence and genomic characterization of grapevine
      asteroid mosaic associated virus.
AB  - In analyzing grapevine clones infected with grapevine red blotch associated
      virus, we identified a small number of isometric particles of approximately 30nm
      in diameter from an enriched fraction of leaf extract. A dominant protein of
      25kDa was isolated from this fraction using SDS-PAGE and was identified by mass
      spectrometry as belonging to grapevine asteroid mosaic associated virus (GAMaV).
      Using a combination of three methods RNA-Seq, sRNA-Seq, and Sanger sequencing of
      RT- and RACE-PCR products, we obtained a full-length genome sequence consisting
      of 6719 nucleotides without the poly(A) tail. The virus possesses all of the
      typical conserved functional domains concordant with the genus Marafivirus and
      lies evolutionarily between citrus sudden death associated virus and oat blue
      dwarf virus. A large shift in RNA-Seq coverage coincided with the predicted
      location of the subgenomic RNA involved in coat protein (CP) expression. Genus
      wide sequence alignments confirmed the cleavage motif LxG(G/A) to be dominant
      between the helicase and RNA dependent RNA polymerase (RdRp), and the RdRp and CP
      domains. A putative overlapping protein (OP) ORF lacking a canonical
      translational start codon was identified with a reading frame context more
      consistent with the putative OPs of tymoviruses and fig fleck associated virus
      than with those of marafiviruses. BLAST analysis of the predicted GAMaV OP showed
      a unique relatedness to the OPs of members of the genus Tymovirus.

PMID- 27720958
TI  - Occasion setting, inhibition, and the contextual control of extinction in
      Pavlovian and instrumental (operant) learning.
AB  - An occasion setter is a stimulus that modulates the ability of another stimulus
      to control behavior. A rich history of experimental investigation has identified
      several important properties that define occasion setters and the conditions that
      give rise to occasion setting. In this paper, we first consider the basic
      hallmarks of occasion setting in Pavlovian conditioning. We then review research
      that has examined the mechanisms underlying the crucial role of context in
      Pavlovian and instrumental extinction. In Pavlovian extinction, evidence suggests
      that the extinction context can function as a negative occasion setter whose role
      is to disambiguate the current meaning of the conditioned stimulus; the
      conditioning context can also function as a positive occasion setter. In operant
      extinction, in contrast, the extinction context may directly inhibit the
      response, and the conditioning context can directly excite it. We outline and
      discuss the key results supporting these distinctions.

PMID- 27720959
TI  - TGF-beta1 and contact mediated suppression by CD4+CD25+CD127- T regulatory cells
      of patients with self-limiting hepatitis E.
AB  - BACKGROUND AND AIM: Literature on the role of Regulatory T cells (Tregs) in acute
      viral infections is limited. Having established that the Tregs in self-limiting
      hepatitis E infection are elevated and functional, this study has focused on
      characterizing the specificity, phenotypes and identifying the molecules or
      factors responsible for enhancement of Treg cells and abrogation of Treg-mediated
      suppression in hepatitis E. METHODS: HEV rORF2p specific (a) Treg frequency,
      subset analysis and expression of surface and intracellular markers on Tregs and
      CFSE based functional analysis by flow cytometry (b) key cytokines quantification
      by multiplex (c) suppressive functional assay in the presence of anti-TGF-beta1
      or anti-IL-10 or both antibodies or Transwell insert or in combination were
      performed on samples from 58 acute patients (AVH-E), 45 recovered individuals
      from hepatitis E and 55 controls. RESULTS: In AVH-E, the increased frequencies of
      Tregs and Teff cells were HEV rORF2p specific and Treg cells were of effector
      memory phenotype. Higher expressions of HEV rORF2p stimulated CTLA-4, GITR, PD1L,
      CD103, CD39, TLR2 and TGF-beta1 molecules on Tregs of AVH-E were observed. Tregs
      produced TGF-beta1 and inhibited the secretion of IFN-gamma. Transwell insert and
      cytokines blocking assays indicated Tregs mediated suppression in AVH-E patients
      is majorly TGF-beta1 mediated and partly cell-cell contact mediated. CONCLUSION:
      Overall, we have identified beneficial involvement of HEV specific, functional
      Tregs and TGF-beta1 as the regulatory molecule responsible for enhancement of
      Tregs in self-limiting HEV infection. Therefore, use of TGF-beta1 as a possible
      supplement for boosting Treg response in recovery from severe hepatitis E needs
      evaluation.